PMID- 16434948
TI  - Outcome after one-stage repair of tetralogy of Fallot.
AB  - AIM: The purpose of this study was to evaluate the outcome after one-stage repair
      of tetralogy of Fallot (TOF). METHODS: Between May 1997 and December 2002, 240
      patients with a median age of 9 months (1 month-48 years) underwent one-stage
      repair of TOF. Closure of ventricular septal defect (VSD) was accomplished
      through the right atrium in 171 (71.3%) patients and through the right ventricle
      in 69 (28.7%) patients. For the reconstruction of the right ventricular outflow
      tract (RVOT), transannular repair was performed in 151 (62.9%) patients, and non
      transannular repair was performed in 89 (37.1%) patients. Follow-up was complete,
      averaging 40+/-17.6 months (3 months-5.8 years). RESULTS: There were 2 (0.8%)
      operative deaths. Between early repair group (age under 6 months) and late repair
      group (age above 6 months), there were no differences in the method of RVOT
      reconstruction (transannular vs non-transannular) and the need for branch
      pulmonary artery angioplasty. Early repair group had more transventricular VSD
      closure than late repair group (46% vs 22%, P < 0.05). Duration of inotropic
      support and intensive care unit (ICU) stay were longer in the early repair group
      (P < 0.05). Five patients required reoperations due to RVOT obstruction (n = 3),
      and residual VSD (n = 2). Kaplan-Meier freedom from reoperation at 5 years was
      98.3+/-1%. Nine patients underwent catheter intervention for branch pulmonary
      artery stenosis. Freedom from reintervention at 5 years was 95.4+/-1.5%. All
      survivors are currently asymptomatic. CONCLUSIONS: One-stage repair of TOF could
      be performed with low mortality and morbidity. Especially, early one-stage repair
      in symptomatic infant could be performed with low risk, eliminating the need for
      palliative procedures.

PMID- 16434949
TI  - A case of primary malignant hemangiopericytoma of the heart with fatal outcome.
AB  - Hemangiopericytoma is a rare, highly vascular tumor which has both malignant and
      benign varieties. We report a case of a 41-year-old man who underwent surgery in
      emergency because of cardiac tamponade. The histopathologic examination of the
      specimens revealed primary malignant cardiac hemangiopericytoma. The patient died
      46 days from the beginning of symptoms and 13 days after surgery.

PMID- 16434950
TI  - Anomalous dual drainage of the right pulmonary veins in a patient with cor
      triatriatum: report of a case without scimitar sign.
AB  - The majority of patients with partial anomalous drainage of pulmonary veins are
      asymptomatic during infancy and childhood. Patients with significant left-to
      right shunt develop symptoms and benefit from early corrective surgery. Anomalous
      pulmonary veins draining into inferior vena cava is very rare and frequently
      encountered in association with scimitar syndrome. The purpose of this case
      report is to describe a non-scimitar patient with cor triatriatum who had
      anomalous dual drainage of right pulmonary veins into inferior vena cava/left
      atrium and anomalous connection of persistent left superior vena cava with a
      common pulmonary venous chamber. The patient underwent an operation with
      redirection of anomalous pulmonary venous drainage into left atrium and ligation
      of persistent left superior vena cava.

PMID- 16434951
TI  - Aortic bulboplasty in acute type A aortic dissection.

PMID- 16434952
TI  - Double primary cardiac tumors: possible association with a variety of cardiac
      diseases.

PMID- 16434953
TI  - Utility of intraoperative frozen section examination in thoracic surgery. A
      review of 721 cases.
AB  - AIM: Intraoperative frozen section examination (FSE) is an important tool for
      determining how extensive a surgical procedure needs to be. In this study we
      reviewed the indications for FSE, the correlation between FSE and postoperative
      histopathology, and the contribution of intraoperative FSE in determining the
      extent of the surgical procedure. METHODS: A total of 744 FSE performed in 721
      patients between January 1995 and January 2004 were reviewed retrospectively. The
      FSE were divided into 7 groups according to the indications of the request for
      frozen section. False positivity and false negativity were evaluated. RESULTS:
      The indications for FSE included intraoperative diagnosis of pulmonary masses
      (311, 41.8%), determination of N2 status with mediastinoscopy and mediastinotomy
      (153, 20.6%), staging of pulmonary carcinomas during the operation (86, 11.6%),
      assessment of the margin of bronchial surgical resection following pulmonary
      resection (54, 7.2%), presence of solitary pulmonary nodules (75, 10.1%),
      presence of mediastinal masses (39, 5.2%), and pleural thickening (26, 3.5%).
      When compared to postoperative paraffin sections, FSE was found to have a 1.9%
      (8) rate of false negatives and a 0.2% (1) rate of false positives (P < 0.001).
      CONCLUSIONS: Intraoperative FSE in thoracic surgery is a rather reliable method.
      When FSE indicates malignancy, it is a valuable guide in directing the extent of
      the ongoing surgical procedure. However, when FSE indicates a benign lesion,
      surgeons should interpret this in the light of the patient's clinical and
      radiological features and the lesion's macroscopic nature when deciding how
      extensive an operation needs to be.

PMID- 16434954
TI  - Thymomas: clinical-pathological correlations.
AB  - AIM: Since World Health Organization (WHO) histologic typing of tumors of the
      thymus publication in 1999 only a few studies correlated this classification with
      the clinical features of the patients. We present the results of a retrospective
      analysis on patients, operated on for a thymoma, whose specimens were available,
      to compare the WHO thymoma histologic classification to the clinical behavior of
      the tumors. METHODS: The specimens of 69 patients, who underwent surgical
      treatment between 1983 and 1998, were analyzed, comparing the clinical features
      of the patients and the hystological typing of the neoplasm, according to the WHO
      classification. A survival analysis of clinical and pathological prognostic
      factors was carried out. RESULTS: The incidence of thymus-related syndrome was
      related to the histological subtype and increases progressively from A to B3,
      while in C subtype the incidence was nihl. With a mean follow-up of 108 months
      (range 54-239 months), we experienced 6 intrathoracic recurrencies, 3 of those
      were intrapleuric and 3 mediastinal. At the last follow-up, 52 patients were
      alive; 1 with disease. Five deaths were related to the tumor (2 mediastinal and 3
      intrapleuric relapses). Actuarial five-year and ten-year survival was 95% and
      88.9%. Because of the absence of deaths related to thymomas in most samples it
      was not possible to perform a comparison among different histological types and
      different clinical stages. CONCLUSIONS: The WHO histologic classification seems
      to correlate with the incidence of thymus related syndromes and the clinical
      stage of Masaoka. Despite the higher incidence of recurrences in type B3 and C
      thymoma the WHO classification did not prove to be a prognostic factor.

PMID- 16434955
TI  - Endotracheal migration of a central venous catheter.
AB  - Subcutaneous infusion ports for prolonged central venous access are commonly used
      for drug administration and parenteral nutrition in a wide range of chronic
      diseases. The extensive use of these devices has to be balanced against its
      complications, some of which potentially life-threatening. We describe the case
      of a patient admitted to our unit with haemoptysis and cough. At bronchoscopy the
      tip of the central venous catheter was discovered protruding into the tracheal
      lumen. The catheter was pulled out from the subcutaneous pouch under simultaneous
      surgical control of the tracheal fistula orifice.

PMID- 16434956
TI  - [The unifying hypothesis on the regulation of body fluid volume. Physiology and
      pathophysiology of fluid homeostasis, with particular regard to cardiac
      decompensation and hepatic cirrhosis].

PMID- 16434957
TI  - [Volume replacement and coagulation impairment].

PMID- 16434958
TI  - [The effectiveness of human albumin in liver failure].

PMID- 16434959
TI  - [Albumin administration: volume replacement or pharmacological treatment?].

PMID- 16434960
TI  - Transient colocalization of X-inactivation centres accompanies the initiation of
      X inactivation.
AB  - The initial differential treatment of the two X chromosomes during X-chromosome
      inactivation is controlled by the X-inactivation centre (Xic). This locus
      determines how many X chromosomes are present in a cell ('counting') and which X
      chromosome will be inactivated in female cells ('choice'). Critical control
      sequences in the Xic include the non-coding RNAs Xist and Tsix, and long-range
      chromatin elements. However, little is known about the process that ensures that
      X inactivation is triggered appropriately when more than one Xic is present in a
      cell. Using three-dimensional fluorescence in situ hybridization (FISH) analysis,
      we showed that the two Xics transiently colocalize, just before X inactivation,
      in differentiating female embryonic stem cells. Using Xic transgenes capable of
      imprinted but not random X inactivation, and Xic deletions that disrupt random X
      inactivation, we demonstrated that Xic colocalization is linked to Xic function
      in random X inactivation. Both long-range sequences and the Tsix element, which
      generates the antisense transcript to Xist, are required for the transient
      interaction of Xics. We propose that transient colocalization of Xics may be
      necessary for a cell to determine Xic number and to ensure the correct initiation
      of X inactivation.

PMID- 16434961
TI  - P53 levels determine outcome during beta-catenin tumor initiation and metastasis
      in the mammary gland and male germ cells.
AB  - beta-Catenin, an oncogene, and P53, a tumor suppressor, are common targets of
      mutation in human cancers. It has been observed that P53 is often inactivated in
      tumors involving beta-catenin activation. In an attempt to model this situation
      in vivo, we crossed the previously characterized MMTV-DeltaN-beta-catenin mouse
      with the P53 knockout mouse. Female multiparous mice that carry the MMTV-DeltaN
      beta-catenin transgene and that are heterozygous for P53 (Tg(DeltaN-betaCat)/+,
      P53+/-) display an increased tumor burden (2.05 vs 1.31 tumors/animal), with a
      generally more advanced pathology, and increased metastatic rate (39 vs 0%)
      relative to transgenic female mice that are wild type for P53 (Tg(DeltaN
      betaCat)/+, P53+/+). These differences were not due to complete loss of P53 as
      only one of 21 tumors demonstrated loss of heterozygosity at the P53 locus.
      Furthermore, no mutations were present in tumors retaining a single wild-type
      allele. Tg(DeltaN-betaCat)/+, P53-/- male mice developed testicular teratomas and
      survived an average of 65 days, whereas non-Tg(DeltaN-betaCat), P53-/- males
      survived an average of 84 days. Sixty-two percent of Tg(DeltaN-betaCat), P53-/-
      mice developed testicular teratomas, whereas only 10% of the non-Tg(DeltaN
      betaCat), P53-/- mice developed these tumors. These results indicate that the
      level of P53 and the tissue of origin are important factors in determining
      outcome of cancer caused by oncogene activation.

PMID- 16434962
TI  - Activation of the NF-kappaB pathway by the leukemogenic TEL-Jak2 and TEL-Abl
      fusion proteins leads to the accumulation of antiapoptotic IAP proteins and
      involves IKKalpha.
AB  - Abnormal activation of tyrosine kinases and of signaling pathways they control
      plays a critical role in the neoplastic process of human hematopoietic
      malignancy. The nuclear factor-kappaB (NF-kappaB) pathway is one of the
      signalings activated by the TEL-Jak2 and TEL-Abl oncoproteins and required for
      their antiapoptotic activity. To define the signal relay responsible for this
      activation, we used mouse embryonic fibroblast (MEF) cells and observed that TEL
      Jak2- and TEL-Abl-mediated NF-kappaB induction was abolished in cells lacking the
      IkappaB kinase (IKK)alpha but not in IKKbeta(-/-) cells. Similar observations
      were performed with oncogenic forms of the FMS-like tyrosine kinase 3 (Flt-3)
      involved in the pathogenesis of one-third of acute myeloid leukemias. Rescue of
      TEL-Jak2-mediated NF-kappaB activation was obtained with a kinase-proficient form
      of IKKalpha in IKKalpha(-/-) MEF. Hematopoietic cells transformed by TEL-Jak2 and
      TEL-Abl showed sustained IKKalpha activity without promotion of NF-kappaB2/p100
      processing, generally associated to IKKalpha functions. Furthermore, IAP1, IAP2
      and XIAP, which are central regulators of the NF-kappaB-mediated survival
      pathway, were highly expressed in cells transformed by these oncoproteins. Our
      results indicate that these oncogenic tyrosine kinases preferentially use an
      IKKalpha-dependent mechanism to induce a persistent NF-kappaB activity and allow
      the production of antiapoptotic effectors that participate to their leukemogenic
      properties.

PMID- 16434964
TI  - Pro-proliferative function of the long isoform of PML-RARalpha involved in acute
      promyelocytic leukemia.
AB  - The promyelocytic leukemia (PML) gene codes for a tumor suppressor protein that
      is associated with distinct subnuclear macromolecular structures called the PML
      bodies. The PML gene is frequently involved in the t(15;17) chromosomal
      translocation of acute promyelocytic leukemia (APL). The translocation results in
      a fusion gene product, PML-RARalpha, in which the PML gene fuses to the retinoic
      acid receptor alpha (RARalpha) gene. PML-RARalpha has been shown to promote
      transcriptional repression of genes involved in myeloid terminal differentiation
      and to disrupt the architecture of PML bodies, a phenotype reversed by treatment
      with all trans retinoic acid (ATRA). However, there are several alternatively
      spliced isoforms of PML-RARalpha. Here, we addressed the differences between the
      short and the long isoforms of PML-RARalpha (L and S) since both are associated
      with APL. We demonstrate that PML-RARalphaL, but not PML-RARalphaS, can directly
      promote cell growth by transcriptionally activating the pro-proliferative gene, c
      fos, in response to mitogenic stimulation. The activity of the PML-RARalphaL is
      completely sensitive to ATRA. We further show that this activation is not via
      direct recruitment of the protein to the c-fos promoter but indirectly by
      altering the chromosomal environment of the c-fos gene, thereby rendering it more
      accessible to the signal induced transcriptional activators. Our results suggest
      that in addition to antagonizing the PML-tumor suppressor or the PML-pro
      apoptotic activity, PML-RARalpha proteins can also directly promote cell growth
      by activating c-fos.

PMID- 16434963
TI  - Thyroid hormone receptors mutated in liver cancer function as distorted
      antimorphs.
AB  - Aberrant thyroid hormone receptors (TRs) are found in over 70% of the human
      hepatocellular carcinomas (HCCs) analysed. To better understand the role(s) of
      these TR mutants in this neoplasia, we analysed a panel of HCC mutant receptors
      for their molecular properties. Virtually all HCC-associated TR mutants tested
      retained the ability to repress target genes in the absence of T3, yet were
      impaired in T3-driven gene activation and functioned as dominant-negative
      inhibitors of wild-type TR activity. Intriguingly, the HCC TRalpha1 mutants
      exerted dominant-negative interference at all T3 concentrations tested, whereas
      the HCC TRbeta1 mutants were dominant-negatives only at low and intermediate T3
      concentrations, reverting to transcriptional activators at higher hormone levels.
      The relative affinity for the SMRT versus N-CoR corepressors was detectably
      altered for several of the HCC mutant TRs, suggesting changes in corepressor
      preference and recruitment compared to wild type. Several of the TRalpha HCC
      mutations also altered the DNA recognition properties of the encoded receptors,
      indicating that these HCC TR mutants may regulate a distinct set of target genes
      from those regulated by wild-type TRs. Finally, whereas wild-type TRs interfere
      with c-Jun/AP-1 function in a T3-dependent fashion and suppress anchorage
      independent growth when ectopically expressed in HepG2 cells, at least certain of
      the HCC mutants did not exert these inhibitory properties. These alterations in
      transcriptional regulation and DNA recognition appear likely to contribute to
      oncogenesis by reprogramming the differentiation and proliferative properties of
      the hepatocytes in which the mutant TRs are expressed.

PMID- 16434965
TI  - Cell type-dependent control of NF-Y activity by TGF-beta.
AB  - Transforming growth factor beta (TGF-beta) is a pluripotent cytokine that
      regulates cell growth and differentiation in a cell type-dependent fashion. TGF
      beta exerts its effects through the activation of several signaling pathways. One
      involves membrane proximal events that lead to nuclear translocation of members
      of the Smad family of transcriptional regulators. TGF-beta can also activate MAPK
      cascades. Here, we show that TGF-beta induces nuclear translocation of the NF-YA
      subunit of the transcription factor NF-Y by a process that requires activation of
      the ERK cascade. This results in increased binding of endogenous NF-Y to
      chromatin and TGF-beta-dependent transcriptional regulation of the NF-Y target
      gene cyclin A2. Interestingly, the kinetics of NF-YA relocalization differs
      between epithelial cells and fibroblasts. NIH3T3 fibroblasts show an elevated
      basal level of phosphorylated p38 and delayed nuclear accumulation of NF-YA after
      TGF-beta treatment. In contrast, MDCK cells show low basal p38 activation, higher
      basal ERK phosphorylation and more rapid localization of NF-YA after induction.
      Thus, NF-Y activation by TGF-beta1 involves ERK1/2 and potentially an interplay
      between MAPK pathways, thereby opening the possibility for finely tuned
      transcriptional regulation.

PMID- 16434966
TI  - The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF signals.
AB  - CHOP (GADD153) is a protein of the C/EBP family of transcriptional regulators,
      which dimerizes with other C/EBP members and changes their DNA-binding and
      transactivation properties. It induces growth arrest and apoptosis after
      endoplasmatic reticulum stress or DNA damage. CHOP is also expressed during early
      embryogenesis and upregulated in tumour tissues with defective Wnt signals. We
      report here that CHOP functions as a specific inhibitor of Wnt/T-cell factor
      (TCF) signalling. CHOP inhibits TCF-dependent transcription in human embryonic
      and colon cancer cell lines. Injection of CHOP mRNA into early Xenopus laevis
      embryos suppresses dorsal organizer formation and inhibits secondary axis
      formation and TCF-dependent transcription in response to Wnt-8, Dishevelled, beta
      Catenin and TCF-VP16. In embryos and human cells, this inhibition depends on the
      N-terminal transactivation domain of CHOP, whereas the C-terminal dimerization
      domain is dispensable. CHOP binds to TCF factors, thereby preventing the binding
      of TCF to its DNA recognition site. Our findings demonstrate a novel function of
      CHOP as a Wnt repressor.

PMID- 16434968
TI  - Erasure of methylation imprint at the promoter and CTCF-binding site upstream of
      H19 in human testicular germ cell tumors of adolescents indicate their fetal germ
      cell origin.
AB  - Genome-wide epigenetic modification plays a crucial role in regulating genome
      functions at critical stages of development. In particular, DNA methylation is
      known to be reprogrammed on a genome-wide level in germ cells and in
      preimplantation embryos, although it is relatively stable in somatic cells. In
      this reprogramming process, the genome becomes demethylated, and methylated de
      novo during later stages of development. Reprogramming of DNA methylation in male
      germ cells has not been fully investigated. Testicular germ cell tumors (TGCTs)
      possess a pluripotential nature and display protean histology from germ cells to
      embryonal and somatic cell differentiation. These properties make TGCT a unique
      model for studying germ cell development and gametogenesis in respect of DNA
      reprogramming. In order to obtain an insight into the epigenetic dynamics of
      TGCTs, we conducted a comprehensive analysis of differential methylated regions
      (DMRs) on H19 and IGF2 in TGCTs compared with testicular malignant lymphomas. In
      the present study, we show that methylation imprint at the promoter and CTCF
      binding site upstream of H19 was completely erased in both seiminomatous and non
      seminomatous TGCTs, whereas differential methylation was observed in testicular
      lymphomas. The erasure of methylation imprint was also observed in TGCTs with
      malignant transformation. We found biallelic unmethylation at the promoter and
      the CTCF-binding site upstream of H19 is required, but not sufficient for the
      biallelic expression of H19 in TGCTs. These data suggest that factors other than
      methylation contribute to transcriptional regulation of imprinted genes in TGCTs.
      The present data have shown that TGCTs carry distinctive epigenetic profiles at
      the core-imprinting domain of H19/IGF2 from other neoplasms of somatic cell
      origin. The data also suggest that both seminomatous and non-seminomatous TGCTs
      carry methylation profiles similar to fetal germ cells, but not adult germ cells,
      indicating the origin of TGCTs as fetal germ cells.

PMID- 16434967
TI  - Sustained trophism of the mammary gland is sufficient to accelerate and
      synchronize development of ErbB2/Neu-induced tumors.
AB  - Epidemiological studies indicate that parity enhances HER2/ErbB2/Neu-induced
      breast tumorigenesis. Furthermore, recent studies using multiparous, ErbB2/Neu
      overexpressing mouse mammary tumor virus (MMTV-Neu) mice have shown that parity
      induces a population of cells that are targeted for ErbB2/Neu-induced
      transformation. Although parity accelerates mammary tumorigenesis, the pattern of
      tumor development in multiparous MMTV-Neu mice remains stochastic, suggesting
      that additional events are required for ErbB2/Neu to cause mammary tumors.
      Whether such events are genetic in nature or reflective of the dynamic hormonal
      control of the gland that occurs with pregnancy remains unclear. We postulated
      that young age at pregnancy initiation or chronic trophic maintenance of mammary
      epithelial cells might provide a cellular environment that significantly
      increases susceptibility to ErbB2/Neu-induced tumorigenesis. MMTV-Neu mice that
      were maintained pregnant or lactating beginning at 3 weeks of age demonstrated
      accelerated tumorigenesis, but this process was still stochastic, indicating that
      early pregnancy does not provide the requisite events of tumorigenesis. However,
      bitransgenic mice that were generated by breeding MMTV-Neu mice with a
      luteinizing hormone-overexpressing mouse model of ovarian hyperstimulation
      developed multifocal mammary tumors in an accelerated, synchronous manner
      compared to virgin MMTV-Neu animals. This synchrony of tumor development in the
      bitransgenic mice suggests that trophic maintenance of the mammary gland provides
      the additional events required for tumor formation and maintains the population
      of cells that are targeted by ErbB2/Neu for transformation. Both the synchrony of
      tumor appearance and the ability to characterize a window of commitment by
      ovariectomy/palpation studies permitted microarray analysis to evaluate changes
      in gene expression over a defined timeline that spans the progression from normal
      to preneoplastic mammary tissue. These approaches led to identification of
      several candidate genes whose expression changes in the mammary gland with
      commitment to ErbB2/Neu-induced tumorigenesis, suggesting that they may either be
      regulated by ErbB2/Neu and/or contribute to tumor formation.

PMID- 16434969
TI  - Protein kinase C delta inhibits Caco-2 cell proliferation by selective changes in
      cell cycle and cell death regulators.
AB  - PKC-delta is a serine/threonine kinase that mediates diverse signal transduction
      pathways. We previously demonstrated that overexpression of PKC-delta slowed the
      G1 progression of Caco-2 colon cancer cells, accelerated apoptosis, and induced
      cellular differentiation. In this study, we further characterized the PKC-delta
      dependent signaling pathways involved in these tumor suppressor actions in Caco-2
      cells overexpressing PKC-delta using a Zn2+ inducible expression vector.
      Consistent with a G1 arrest, increased expression of PKC-delta caused rapid and
      significant downregulation of cyclin D1 and cyclin E proteins (50% decreases,
      P<0.05), while mRNA levels remained unchanged. The PKC agonist, phorbol 12
      myristate 13-acetate (TPA, 100 nM, 4 h), induced two-fold higher protein and mRNA
      levels of p21(Waf1), a cyclin-dependent kinase (cdk) inhibitor in PKC-delta
      transfectants compared with empty vector (EV) transfected cells, whereas the PKC
      delta specific inhibitor rottlerin (3 microM) or knockdown of this isoenzyme with
      specific siRNA oligonucleotides blocked p21(Waf1) expression. Concomitantly,
      compared to EV control cells, PKC-delta upregulation decreased cyclin D1 and
      cyclin E proteins co-immunoprecipitating with cdk6 and cdk2, respectively. In
      addition, overexpression of PKC-delta increased binding of cdk inhibitor
      p27(Kip1) to cdk4. These alterations in cyclin-cdks and their inhibitors are
      predicted to decrease G1 cyclin kinase activity. As an independent confirmation
      of the direct role PKC-delta plays in cell growth and cell cycle regulation, we
      knocked down PKC-delta using specific siRNA oligonucleotides. PKC-delta specific
      siRNA oligonucleotides, but not irrelevant control oligonucleotides, inhibited
      PKC-delta protein by more than 80% in Caco-2 cells. Moreover, PKC-delta knockdown
      enhanced cell proliferation ( approximately 1.4-2-fold, P<0.05) and concomitantly
      increased cyclin D1 and cyclin E expression ( approximately 1.7-fold, P<0.05).
      This was a specific effect, as nontargeted PKC-zeta was not changed by PKC-delta
      siRNA oligonucleotides. Consistent with accelerated apoptosis in PKC-delta
      transfectants, compared to EV cells, PKC-delta upregulation increased
      proapoptotic regulator Bax two-fold at mRNA and protein levels, while
      antiapoptotic Bcl-2 protein was decreased by 50% at a post-transcriptional level.
      PKC-delta specific siRNA oligonucleotides inhibited Bax protein expression by
      more than 50%, indicating that PKC-delta regulates apoptosis through Bax. Taken
      together, these results elucidate two critical mechanisms regulated by PKC-delta
      that inhibit cell cycle progression and enhance apoptosis in colon cancer cells.
      We postulate these antiproliferative pathways mediate an important tumor
      suppressor function for PKC-delta in colonic carcinogenesis.

PMID- 16434970
TI  - Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt.
AB  - Proapoptotic nuclear receptor family member Nur77 translocates from the nucleus
      to the mitochondria, where it interacts with Bcl-2 to trigger apoptosis. Nur77
      translocation is induced by certain apoptotic stimuli, including the synthetic
      retinoid-related 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid
      (AHPN)/CD437 class. In this study, we investigated the molecular mechanism by
      which AHPN/CD437 analog (E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic
      acid (3-Cl-AHPC) induces Nur77 nuclear export. Our results demonstrate that 3-Cl
      AHPC effectively activated Jun N-terminal kinase (JNK), which phosphorylates
      Nur77. Inhibition of JNK activation by a JNK inhibitor suppressed 3-Cl-AHPC
      induced Nur77 nuclear export and apoptosis. In addition, several JNK upstream
      activators, including the phorbol ester TPA, anisomycin and MAPK kinase kinase-1
      (MEKK1), phosphorylated Nur77 and induced its nuclear export. However, Nur77
      phosphorylation by JNK, although essential, was not sufficient for inducing Nur77
      nuclear export. Induction of Nur77 nuclear export by MEKK1 required a prolonged
      MEKK1 activation and was attenuated by Akt activation. Expression of
      constitutively active Akt prevented MEKK1-induced Nur77 nuclear export.
      Conversely, transfection of dominant-negative Akt or treatment with a
      phosphatidylinositol 3-kinase (PI3-K) inhibitor accelerated MEKK1-induced Nur77
      nuclear export. Furthermore, mutation of an Akt phosphorylation residue Ser351 in
      Nur77 abolished the effect of Akt or the PI3-K inhibitor. Together, our results
      demonstrate that both activation of JNK and inhibition of Akt play a role in
      translocation of Nur77 from the nucleus to the cytoplasm.

PMID- 16434971
TI  - B-Raf and C-Raf are required for Ras-stimulated p42 MAP kinase activation in
      Xenopus egg extracts.
AB  - During mitosis, a select pool of MEK1 and p42/p44 MAPK becomes activated at the
      kinetochores and spindle poles, without substantial activation of the bulk of the
      cytoplasmic p42/p44 MAPK. Recently, we set out to identify the MAP kinase kinase
      kinase (MAPKKK) responsible for this mitotic activation, using cyclin-treated
      Xenopus egg extracts as a model system, and presented evidence that Mos was the
      relevant MAPKKK . However, a second MAPKKK distinct from Mos was readily
      detectable as well. Here, we partially purify this second MAPKKK and identify it
      as B-Raf. No changes in the activity of B-Raf were detectable during progesterone
      induced oocyte maturation, after egg fertilization, or during the early embryonic
      cell cycle, arguing against a role for B-Raf in the mitotic activation of MEK1
      and p42 MAPK. Ras proteins can bring about activation of MEK1 and p42 MAPK in
      extracts, and Ras may contribute to signaling from the classical progesterone
      receptor during oocyte maturation and from receptor tyrosine kinases during early
      embryogenesis. We found that both B-Raf and C-Raf, but not Mos, are required for
      Ras-induced MEK1 and p42 MAPK activation. These data indicate that two upstream
      stimuli, active Ras and active Cdc2, utilize different MAPKKKs to activate MEK1
      and p42 MAPK.

PMID- 16434972
TI  - E2F1 induces MRN foci formation and a cell cycle checkpoint response in human
      fibroblasts.
AB  - Deregulation of the Rb/E2F pathway in human fibroblasts results in an E2F1
      mediated apoptosis dependent on Atm, Nbs1, Chk2 and p53. Here, we show that E2F1
      expression results in MRN foci formation, which is independent of the Nbs1
      interacting region and the DNA-binding domain of E2F1. E2F1-induced MRN foci are
      similar to irradiation-induced foci (IRIF) that result from double-strand DNA
      breaks because they correlate with 53BP1 and gammaH2AX foci, do not form in NBS
      cells, do form in AT cells and do not correlate with cell cycle entry. In fact,
      we find that in human fibroblasts deregulated E2F1 causes a G1 arrest, blocking
      serum-induced cell cycle progression, in part through an
      Nbs1/53BP1/p53/p21(WAF1/CIP1) checkpoint pathway. This checkpoint protects
      against apoptosis because depletion of 53BP1 or p21(WAF1/CIP1) increases both the
      rate and extent of apoptosis. Nbs1 and p53 contribute to both checkpoint and
      apoptosis pathways. These results suggest that E2F1-induced foci generate a cell
      cycle checkpoint that, with sustained E2F1 activity, eventually yields to
      apoptosis. Uncontrolled proliferation due to Rb/E2F deregulation as well as
      inactivation of both checkpoint and apoptosis programs would then be required for
      transformation of normal cells to tumor cells.

PMID- 16434973
TI  - Androgen receptor activity is inhibited in response to genotoxic agents in a p53
      independent manner.
AB  - The androgen receptor (AR) is fundamental to androgen signalling within the
      prostate gland, and deregulation of its activity is frequently linked to the
      development of prostate cancer. Advanced prostate cancer is often treated with
      chemotherapy and most of these drugs exert their function by generating genotoxic
      stress such as DNA damage. We have investigated here the effects of genotoxic
      agents used in chemotherapeutic regimens on AR function and expression. We have
      discovered that endogenous AR activity in LNCaP cells is inhibited in response to
      the chemotherapeutic agents etoposide and cisplatin. This loss of AR activity is
      not caused by a change in cell cycle distribution, a change in subcellular
      localisation of the AR nor by induction of apoptosis. In addition, we found that
      inhibition of AR activity in response to genotoxic stress is independent of p53
      function. Interestingly, our studies revealed that genotoxic stress inhibits the
      hormone-stimulated recruitment of AR to androgen response elements. Thus, we
      report for the first time a mechanism by which the AR activity is inhibited in
      response to different chemotherapeutic agents.

PMID- 16434974
TI  - The UVB-induced gene expression profile of human epidermis in vivo is different
      from that of cultured keratinocytes.
AB  - In order to obtain a comprehensive picture of the molecular events regulating
      cutaneous photodamage of intact human epidermis, suction blister roofs obtained
      after a single dose of in vivo ultraviolet (UV)B exposure were used for
      microarray profiling. We found a changed expression of 619 genes. Half of the UVB
      regulated genes had returned to pre-exposure baseline levels at 72 h,
      underscoring the transient character of the molecular cutaneous UVB response. Of
      special interest was our finding that several of the central p53 target genes
      remained unaffected following UVB exposure in spite of p53 protein accumulation.
      We next compared the in vivo expression profiles of epidermal sheets to that of
      cultured human epidermal keratinocytes exposed to UVB in vitro. We found 1931
      genes that differed in their expression profiles between the two groups. The
      expression profile in intact epidemis was geared mainly towards DNA repair,
      whereas cultured keratinocytes responded predominantly by activating genes
      associated with cell-cycle arrest and apoptosis. These differences in expression
      profiles might reflect differences between mature differentiating keratinocytes
      in the suprabasal epidermal layers versus exponentially proliferating
      keratinocytes in cell culture. Our findings show that extreme care should be
      taken when extrapolating from findings based on keratinocyte cultures to changes
      in intact epidermis.

PMID- 16434975
TI  - The R273H p53 mutation can facilitate the androgen-independent growth of LNCaP by
      a mechanism that involves H2 relaxin and its cognate receptor LGR7.
AB  - Mutations in p53 occur at a rate of approximately 70% in hormone-refractory
      prostate cancer (CaP), suggesting that p53 mutations facilitate the progression
      of CaP to androgen-independent (AI) growth. We have previously reported that
      transfection of p53 gain of function mutant alleles into LNCaP, an androgen
      sensitive cell line, allows for AI growth of LNCaP in vitro. We herein confirm
      the in vivo relevance of those findings by demonstrating that the R273H p53
      mutation (p53(R273H)) facilitates AI growth in castrated nude mice. In addition,
      we demonstrate that H2 relaxin is responsible for facilitating p53(R273H)
      mediated AI CaP. H2 relaxin is overexpressed in the LNCaP-R273H subline.
      Downregulation of H2 relaxin expression results in significant inhibition of AI
      growth, whereas addition of recombinant human H2 relaxin to parental LNCaP
      promotes AI growth. Inhibition of AI growth was also achieved by blocking
      expression of LGR7, the cognate receptor of H2 relaxin. Chromatin
      immunoprecipitation analysis was used to demonstrate that p53(R273H) binds
      directly to the relaxin promoter, further confirming a role for H2 relaxin
      signaling in p53(R273H)-mediated AI CaP. Lastly, we used a reporter gene assay to
      demonstrate that H2 relaxin can induce the expression of prostate-specific
      antigen via an androgen receptor-mediated pathway.

PMID- 16434976
TI  - Lack of p53 induction in fish cells by model chemotherapeutics.
AB  - Although p53 has been extensively studied in mammalian models, relatively little
      is known about its specific function in lower vertebrates. It has long been
      assumed that p53 pathways characterized in mammals apply to other vertebrates as
      well. Fish provide a useful model for the study of environmental carcinogenesis,
      and populations of fish inhabiting highly polluted environments provide
      information on the etiology of pollutant-mediated cancer. In this study, we
      investigated p53 protein and apoptosis induction in PLHC-1 (desert topminnow
      hepatocellular carcinoma), RTL-W1 (rainbow trout normal liver), and primary
      rainbow trout hepatocytes exposed to model chemotherapeutics. All of the
      chemicals used in these studies have been demonstrated to increase p53 protein
      levels and induce apoptosis in mammalian cell lines. In contrast, PLHC-1 p53
      protein was not induced in response to any model mammalian p53 inducers following
      24 h exposures. Additionally, both trout cell types demonstrated this same lack
      of p53 induction upon exposure to model chemotherapeutic drugs. PLHC-1 cells
      demonstrated an induction of apoptosis as measured by caspase-3 activation
      following exposure to all of the chemotherapeutics tested. Our results suggest
      that fish p53 may be activated differently from that of their mammalian
      counterparts, and that important differences may exist between phyla in the
      function and regulation of p53 as well as other mechanisms involved in
      environmental carcinogenesis.

PMID- 16434977
TI  - Activation of p300 histone acetyltransferase activity and acetylation of the
      androgen receptor by bombesin in prostate cancer cells.
AB  - Androgen receptor signaling in prostate cancer cells is augmented by the androgen
      receptor (AR) coactivator p300, which transactivates and acetylates the AR in the
      presence of dihydrotestosterone (DHT). As prostate cancer (PC) cells progress to
      androgen independence, AR signaling remains intact, indicating that other factors
      stimulate AR activities in the absence of androgen. We previously reported that
      neuropeptide growth factors could transactivate the AR in the presence of very
      low concentrations of DHT. Here, we examine the involvement of p300 in
      neuropeptide activation of AR signaling. Transfection of increasing
      concentrations of p300 in the presence of bombesin into PC-3 cells resulted in a
      linear increase in AR transactivation, suggesting that p300 acts as a coactivator
      in neuropeptide-mediated AR transactivation. P300 is endowed with histone
      acetyltransferase (HAT) activity. Therefore, we examine the effect of bombesin on
      p300 HAT activity. At 4 h after the addition of bombesin, p300 HAT activity
      increased 2.0-fold (P<0.01). Incubation with neutral endopeptidase, which
      degrades bombesin, or bombesin receptor antagonists blocked bombesin-induced p300
      HAT activity. To explore the potential signaling pathways involved in bombesin
      induced p300 HAT activity, we examined Src and PKCdelta pathways that mediate
      bombesin signaling. Inhibitors of Src kinase activity or Src kinase siRNA blocked
      bombesin-induced p300 HAT activity, whereas PKCdelta inhibitors or PKCdelta siRNA
      significantly increased bombesin-induced p300 HAT activity suggesting that Src
      kinase and PKCdelta kinase are involved in the regulation of p300 HAT activity.
      As AR is acetylated in the presence of 100 nM DHT, we next examined whether
      bombesin-induced p300 HAT activity would result in enhanced AR acetylation.
      Bombesin-induced AR acetylation at the same motif KLKK observed in DHT-induced
      acetylation. Elimination of p300 using p300 siRNA reduced AR acetylation,
      demonstrating that AR acetylation was mediated by p300. AR acetylation results in
      AR transactivation and the expression of the AR-regulated gene prostate-specific
      antigen (PSA). Therefore, we examined bombesin-induced AR transactivation and PSA
      expression in the presence and absence of p300 siRNA and found inhibition of p300
      expression reduced bombesin-induced AR transactivation and PSA expression.
      Together these results demonstrate that bombesin, via Src and PKCdelta signaling
      pathways, activates p300 HAT activity which leads to enhanced acetylation of AR
      resulting in increased expression of AR-regulated genes.

PMID- 16434982
TI  - Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle
      progression, nitric oxide pathway and patient survival.
AB  - Emerging evidences suggest the existence of a new mode of epidermal growth factor
      receptor (EGFR) signalling pathway in which activated EGFR undergoes nuclear
      translocalization and subsequently regulates gene expression and potentially
      mediates other cellular processes. This signalling route is distinct from the
      better-characterized, traditional EGFR pathway that involves transduction of
      mitogenic signals through activation of multiple signalling cascades.
      Transcriptional activity of nuclear EGFR appears to depend on its C-terminal
      transactivation domain and its physical and functional interaction with other
      transcription factors that contain DNA-binding activity. Likely via its ability
      to upregulate gene expression, nuclear EGFR pathway is associated with major
      characteristics of more aggressive tumours: increased proliferative potential,
      nitric oxide synthesis, and accelerated G1/S cell cycle progression. A role of
      nuclear EGFR in prognostic prediction is further suggested in patients with
      breast carcinomas and oropharyngeal squamous cell carcinomas. It is noted that
      significant advances were made towards the knowledge of the nuclear EGFR pathway;
      however, many aspects of this new pathway remain unresolved and will be discussed
      in this review. As a number of other receptor tyrosine kinases (RTKs) and
      cytokine receptors also undergo similar nuclear translocalization, a better
      understanding of the physiological and malignant nature of the nuclear EGFR
      pathway will likely shed light into the biology of cancer with nuclear RTKs.

PMID- 16434983
TI  - Refining the role of laparoscopy and laparoscopic ultrasound in the staging of
      presumed pancreatic head and ampullary tumours.
AB  - Laparoscopy and laparoscopic ultrasound have been validated previously as staging
      tools for pancreatic cancer. The aim of this study was to identify if assessment
      of vascular involvement with abdominal computed tomography (CT) would allow
      refinement of the selection criteria for laparoscopy and laparoscopic ultrasound
      (LUS). The details of patients staged with LUS and abdominal CT were obtained
      from the unit's pancreatic cancer database. A CT grade (O, A-F) of vascular
      involvement was recorded by a single radiologist. Of 152 patients, who underwent
      a LUS, 56 (37%) had unresectable disease. Three of 26 (12%) patients with CT
      grade O, 27 of 88 (31%) patients with CT grade A to D, 17 of 29 (59%) patients
      with CT grade E and all nine patients with CT grade F were found to have
      unresectable disease. In all, 24% of patients with tumours <3 cm were found to
      have unresectable disease. In those patients with tumours considered
      unresectable, local vascular involvement was found in 56% of patients and
      vascular involvement with metastatic disease in 17%, while 20% of patients had
      liver metastases alone and 5% had isolated peritoneal metastases. The remaining
      patient was deemed unfit for resection. Selective use of laparoscopic ultrasound
      is indicated in the staging of periampullary tumours with CT grades A to D.

PMID- 16434986
TI  - Calculating age-adjusted cancer survival estimates when age-specific data are
      sparse: an empirical evaluation of various methods.
AB  - We evaluated empirically the performance of various methods of calculating age
      adjusted survival estimates when age-specific data are sparse. We have
      illustrated that a recently proposed alternative method of age adjustment
      involving the use of balanced age groups or age truncation may be useful for
      enhancing calculability and reliability of adjusted survival estimates.

PMID- 16434984
TI  - Monocytes and neutrophils as 'bad guys' for the outcome of interleukin-2 with and
      without histamine in metastatic renal cell carcinoma--results from a randomised
      phase II trial.
AB  - Histamine (HDC) inhibits formation and release of phagocyte-derived reactive
      oxygen species, and thereby protects natural killer (NK) and T cells against
      oxidative damage. Thus, the addition of histamine may potentially improve the
      efficacy of interleukin-2 (IL-2). We have explored this potential mechanism
      clinically in two randomised phase II trials in metastatic renal cell carcinoma
      (mRCC). In parallel with the clinical trial in Denmark (n=63), we obtained serial
      blood samples and tumour biopsies searching for a potential histamine effect in
      situ. At baseline and on-treatment weeks 3 and 8, we monitored the 'good guys'
      (i.e. NK and T cells) and 'bad guys' (i.e. monocytes/macrophages and neutrophils)
      simultaneously in blood (n=59) and tumour tissue (n=44). Patients with high
      number of monocytes and neutrophils in peripheral blood had very poor survival,
      with apparently no benefit from either IL-2 alone or IL-2/HDC treatment. Blood
      monocytes (r=-0.36, P=0.01) and neutrophils (r=-0.46, P=0.001) were negatively
      correlated with cytotoxicity, whereas blood NK cells were positively correlated
      with cytotoxicity (r=0.39, P=0.002). Treatment with IL-2 alone resulted in a
      significantly higher number of circulating monocytes (P=0.037) and intratumoral
      macrophages (P=0.005) compared with baseline. In contrast, IL-2/HDC resulted in
      an unchanged number of circulating monocytes and intratumoral macrophages, and in
      addition, a significantly increased number of intratumoral CD56(+) NK cells
      (P=0.008) and CD8(+) T cells (P=0.019) compared with baseline. The study provides
      evidence that circulating monocytes and neutrophils are powerful negative
      prognostic factors for IL-2-based immunotherapy and establishes a biological
      rationale for the potential use of histamine in conjunction with IL-2 in mRCC.

PMID- 16434987
TI  - Experimental designs for phase I and phase I/II dose-finding studies.
AB  - We review the rationale behind the statistical design of dose-finding studies as
      used in phase I and phase I/II clinical trials. We underline what the objectives
      of such dose-finding studies should be and why the widely used standard design
      fails to meet any of these objectives. The standard design is a "memoryless"
      design and we discuss how this impacts on practical behaviour. Designs introduced
      over the last two decades can be viewed as designs with memory and we discuss how
      these designs are superior to memoryless designs. By superior we mean that they
      require less patients overall, less patients to attain the maximum tolerated dose
      (MTD), and concentrate a higher percentage of patients at and near to the MTD. We
      reanalyse some recently published studies in order to provide support to our
      contention that markedly better results could have been achieved had a design
      with memory been used instead of a memoryless design.

PMID- 16434988
TI  - Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic
      adenocarcinoma: a phase II study.
AB  - Gemcitabine and oxaliplatin (GEMOX) are active as first-line therapy against
      advanced pancreatic cancer. This study aims to evaluate the activity and
      tolerability of this combination in patients refractory to standard gemcitabine
      (GEM). A total of 33 patients (median age of 57) were included with locally
      advanced and metastatic evaluable diseases, who had progressed during or
      following GEM therapy. The GEMOX regimen consisted of 1000 mg m(-2) of GEM at a
      100-min infusion on day 1, followed on day 2 by 100 mg m(-2) of oxaliplatin at a
      2-h infusion; a cycle that was given every 2 weeks. All patients received at
      least one cycle of GEMOX (median 5; range 1-29). Response by 31 evaluable
      patients was as follows: PR: 7/31(22.6%), s.d. > or = 8 weeks: 11/31(35.5%), s.d.
      < 8 weeks: 1/31(3.2%), PD: 12/31(38.7%). Median duration of response and TTP were
      4.5 and 4.2 months, respectively. Median survival was 6 months (range 0.5-21).
      Clinical benefit response was observed in 17/31 patients (54.8%). Grade III/IV
      non-neurologic toxicities occurred in 12/33 patients (36.3%), and grade I, II,
      and III neuropathy in 17(51%), 3(9%), and 4(12%) patients, respectively. GEMOX is
      a well-tolerated, active regimen that may provide a benefit to patients with
      advanced pancreatic cancer after progression following standard gemcitabine
      treatment.

PMID- 16434989
TI  - Should aromatase inhibitors be used as initial adjuvant treatment or sequenced
      after tamoxifen?
AB  - A number of trials have studied the value of aromatase inhibitors (AIs) for the
      adjuvant treatment of early hormone-responsive postmenopausal breast cancer.
      Three different AIs have been used and they have been compared as initial
      treatment (two trials) or after 2-3 years of tamoxifen (four trials), in both
      cases against a standard arm of 5 years of tamoxifen. In addition, two trials
      have evaluated AIs against no treatment after 5 years of tamoxifen. In all
      circumstances, the AIs have demonstrated superior efficacy. However, no results
      are currently available for the key question, that is - is it better to start
      initially with an AI or use it sequentially after 2 years of tamoxifen? Here, we
      review the trial results and present two models, which address this issue. The
      models clearly show that early treatment with an AI is superior to using it after
      5 years of tamoxifen. They also favour an upfront strategy to sequencing after 2
      years of tamoxifen, but in this case the differences are small and model
      dependent. A key question is whether AIs have substantially better efficacy than
      tamoxifen for ER-positive-PgR-negative tumours, where the data are currently
      contradictory. A mechanism explaining why greater efficacy might be so is
      proposed. Further results from ongoing trials will be needed to resolve this
      issue.

PMID- 16434990
TI  - Angiotensin II type 1 receptor expression in ovarian cancer and its correlation
      with tumour angiogenesis and patient survival.
AB  - Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as
      a growth-promoting and angiogenic factor via type 1 angiotensin II receptors
      (AT(1)R). We have recently demonstrated that angiotensin II enhanced tumour cell
      invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in
      ovarian cancer cell lines in vitro. The aim of the present study was to determine
      whether AT1R expression in ovarian cancer is correlated with clinicopathological
      parameters, angiogenic factors and patient survival. Immunohistochemical staining
      for AT1R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed
      in ovarian cancer tissues (n = 67). Intratumour microvessel density (MVD) was
      analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II
      receptors were expressed in 85% of the cases examined, of which 55% were strongly
      positive. Type 1 angiotensin II receptors expression was positively correlated
      with VEGF expression intensity and MVD, but not with histological subtype, grade,
      FIGO stage or PCNA labelling index. In patients who had positive staining for
      AT1R, the overall survival and progression-free survival were significantly poor
      (P = 0.041 and 0.017, respectively) as compared to those in patients who had
      negative staining for AT1R, although VEGF, but not AT1R, was an independent
      prognostic factor on multivariate analysis. These results demonstrated that AT1R
      correlated with tumour angiogenesis and poor patient outcome in ovarian cancer,
      suggesting its clinical potential for a novel molecular target in strategies for
      ovarian cancer treatment.

PMID- 16434991
TI  - Feasibility of familial PSA screening: psychosocial issues and screening
      adherence.
AB  - This study examined factors that predict psychological morbidity and screening
      adherence in first-degree relatives (FDRs) taking part in a familial PSA
      screening study. Prostate cancer patients (index cases - ICs) who gave consent
      for their FDRs to be contacted for a familial PSA screening study to contact
      their FDRs were also asked permission to invite these FDRs into a linked
      psychosocial study. Participants were assessed on measures of psychological
      morbidity (including the General Health Questionnaire; Cancer Worry Scale; Health
      Anxiety Questionnaire; Impact of Events Scale); and perceived benefits and
      barriers, knowledge; perceived risk/susceptibility; family history; and socio
      demographics. Of 255 ICs, 155 (61%) consented to their FDRs being contacted. Of
      207 FDRs approached, 128 (62%) consented and completed questionnaires.
      Multivariate logistic regression revealed that health anxiety, perceived risk and
      subjective stress predicted higher cancer worry (P = 0.05). Measures of
      psychological morbidity did not predict screening adherence. Only past screening
      behaviour reliably predicted adherence to familial screening (P = 0.05). First
      degree relatives entering the linked familial PSA screening programme do not, in
      general, have high levels of psychological morbidity. However, a small number of
      men exhibited psychological distress.

PMID- 16434993
TI  - Malignant spinal cord compression: a retrospective audit of clinical practice at
      a UK regional cancer centre.
AB  - Malignant Spinal Cord Compression (MSCC) is a particularly challenging area of
      cancer care where early diagnosis and expert multiprofessional care and
      rehabilitation, are paramount in optimising quality of life. This audit reports
      data collected retrospectively over a period of 12 months on patients with MSCC
      referred to the West of Scotland Cancer Centre (n = 174). It was carried out to
      build on the work of the Clinical Resource and Audit Group (CRAG) and to examine
      current practice for symptom assessment, multiprofessional care and
      rehabilitation of patients with MSCC admitted to the cancer centre. Areas of
      concern include poor assessment of pain, the poor ambulatory status of patients
      on admission and the lack of clear plans for mobilisation and rehabilitation for
      the majority of patients. Recommendations include the development of regional
      guidelines for referral, treatment and rehabilitation, and the development of a
      pathway of care for use in all care settings across the region, together with
      improvements for use in patient information, staff education, audit and research.
      These are now being taken forward through the West of Scotland Cancer Network
      with dedicated funding from Macmillan Cancer Relief.

PMID- 16434992
TI  - Prognostic impact of multidrug resistance gene expression on the management of
      breast cancer in the context of adjuvant therapy based on a series of 171
      patients.
AB  - Study of the prognostic impact of multidrug resistance gene expression in the
      management of breast cancer in the context of adjuvant therapy. This study
      involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/
      hormonal therapy (mean follow-up: 55 months). We studied the expression of
      multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein
      (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised,
      semiquantitative rt-PCR method performed on frozen samples of breast cancer
      tissue. Patients were classified as presenting low or high levels of expression
      of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff
      Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene
      expression levels on 5-year disease-free survival (DFS) and overall survival (OS)
      was studied by univariate and multivariate Cox analysis. No statistically
      significant correlation was demonstrated between MDR1, MRP1 and GSTP1
      expressions. On univariate analysis, DFS was significantly decreased in a context
      of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or =
      5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P
      = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and
      the presence of ER remained independent prognostic factors for DFS. GSTP1
      expression did not affect OS. The levels of MDR1 and MRP1 expression had no
      significant influence on DFS or OS. GSTP1 expression can be considered to be an
      independent prognostic factor for DFS in patients receiving adjuvant chemotherapy
      for breast cancer.

PMID- 16434994
TI  - Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with
      higher tumour grades and positive nodal status.
AB  - Human kallikrein 14 (KLK14) is a steroid hormone-regulated member of the tissue
      kallikrein family of serine proteases, for which a prognostic and diagnostic
      value in breast cancer has been suggested. To further characterise the value of
      KLK14 as a breast tumour marker, we have carefully analysed KLK14 expression in
      normal breast tissue and breast cancer both on the RNA level by real-time RT-PCR
      (n = 39), and on the protein level (n = 127) using a KLK14-specific antibody for
      immunohistochemistry. We correlated KLK14 protein expression data with available
      clinico-pathological parameters (mean follow-up time was 55 months) including
      patient prognosis. KLK14 RNA expression as quantified by real-time RT-PCR was
      significantly more abundant in breast tumours compared to normal breast tissue (P
      = 0.027), an issue that had not been clarified recently. Concordantly with the
      RNA data, cytoplasmic KLK14 protein expression was significantly higher in
      invasive breast carcinomas compared to normal breast tissues (P = 0.003).
      Furthermore, KLK14 protein expression was associated with higher tumour grade (P
      = 0.041) and positive nodal status (P = 0.045) but was not significantly
      associated with shortened disease-free or overall patient survival time in
      univariate analyses. We conclude that KLK14 is clearly overexpressed in breast
      cancer in comparison to normal breast tissues and is positively associated with
      conventional parameters of tumour aggressiveness, but due to a missing
      association with survival times, the use of KLK14 immunohistochemistry as a
      prognostic marker in breast cancer is questionable.

PMID- 16434995
TI  - TRAIL sensitisation by arsenic trioxide is caspase-8 dependent and involves
      modulation of death receptor components and Akt.
AB  - The majority of leukaemic cells are resistant to apoptosis induced by tumour
      necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we show that
      sublethal concentrations of arsenic trioxide (ATO) specifically enhanced TRAIL
      induced apoptosis in leukaemic but not in other tumour cell lines. The
      combination of ATO and TRAIL synergistically enhanced cleavage of caspase-8,
      which was blocked by the caspase inhibitor IETD.fmk as well as in cells deficient
      for caspase-8, suggesting a requirement for the death-inducing signalling
      complex. Arsenic trioxide led to increased cell surface expression of DR5 (death
      receptor 5), inhibition of the serine/threonine kinase Akt and downregulation of
      the short isoform of FLIP (FLICE-inhibitory protein, FLIPS). Inhibition of the
      phosphatidylinositol 3 kinase (PI3K) was equally efficient in sensitising
      leukaemic cells to TRAIL with similar effects on DR5 and FLIPS expression,
      suggesting that ATO may in part act through inhibition of the PI3K/Akt signalling
      pathway. These results indicate that the enhancement in TRAIL-mediated apoptosis
      induced by ATO is due to alteration in the levels of multiple components and
      regulators of the death receptor-mediated pathway. These findings offer a
      promising and novel strategy involving a combination of TRAIL and ATO, or more
      specific Akt inhibitors in the treatment of various haematopoietic malignancies.

PMID- 16434996
TI  - BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and
      genistein in breast and prostate cancer cells.
AB  - Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals derived
      from cruciferous vegetables and soy, respectively, with potential cancer
      prevention activity for hormone-responsive tumours (e.g., breast and prostate
      cancers). Previously, we showed that I3C induces BRCA1 expression and that both
      I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen receptor (ER-alpha)
      activity in human breast cancer cells. We now report that both I3C and genistein
      induce the expression of both breast cancer susceptibility genes (BRCA1 and
      BRCA2) in breast (MCF-7 and T47D) and prostate (DU-145 and LNCaP) cancer cell
      types, in a time- and dose-dependent fashion. Induction of the BRCA genes
      occurred at low doses of I3C (20 microM) and genistein (0.5-1.0 microM),
      suggesting potential relevance to cancer prevention. A combination of I3C and
      genistein gave greater than expected induction of BRCA expression. Studies using
      small interfering RNAs (siRNAs) and BRCA expression vectors suggest that the
      phytochemical induction of BRCA2 is due, in part, to BRCA1. Functional studies
      suggest that I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2.
      Inhibition of E2-stimulated ER-alpha activity by I3C and genistein was dependent
      upon BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by
      I3C and genistein was partially reversed by BRCA1-siRNA. Finally, we provide
      evidence suggesting that the phytochemical induction of BRCA1 expression is due,
      in part, to endoplasmic reticulum stress response signalling. These findings
      suggest that the BRCA genes are molecular targets for some of the activities of
      I3C and genistein.

PMID- 16434998
TI  - Highly discrepant proportions of female and male Scandinavian and British Isles
      ancestry within the isolated population of the Faroe Islands.
AB  - The Faroe Islands in the North Atlantic Ocean are inhabited by a small
      population, whose origin is thought to date back to the Viking Age. Historical,
      archaeological and linguistic evidence indicates that the present population of
      the Faroe Islands may have a mixture of Scandinavian and British Isles ancestry.
      In the present study we used 122 new and 19 previously published hypervariable
      region I sequences of the mitochondrial control region to analyse the genetic
      diversity of the Faroese population and compare it with other populations in the
      North Atlantic region. The analyses suggested that the Faroese mtDNA pool has
      been affected by genetic drift, and is among the most homogenous and isolated in
      the North Atlantic region. This will have implications for attempts to locate
      genes for complex disorders. To obtain estimates of Scandinavian vs British Isles
      ancestry proportions, we applied a frequency-based admixture approach taking
      private haplotypes into account by the use of phylogenetic information. While
      previous studies have suggested an excess of Scandinavian ancestry among the male
      settlers of the Faroe Islands, the current study indicates an excess of British
      Isles ancestry among the female settlers of the Faroe Islands. Compared to other
      admixed populations of the North Atlantic region, the population of the Faroe
      Islands appears to have the highest level of asymmetry in Scandinavian vs British
      Isles ancestry proportions among female and male settlers of the archipelago.

PMID- 16434997
TI  - The feasibility and results of a population-based approach to evaluating prostate
      specific antigen screening for prostate cancer in men with a raised familial
      risk.
AB  - The feasibility of a population-based evaluation of screening for prostate cancer
      in men with a raised familial risk was investigated by studying reasons for non
      participation and uptake rates according to postal recruitment and clinic
      contact. The levels of prostate-specific antigen (PSA) and the positive
      predictive values (PPV) for cancer in men referred with a raised PSA and in those
      biopsied were analysed. First-degree male relatives (FDRs) were identified
      through index cases (ICs): patients living in two regions of England and
      diagnosed with prostate cancer at age < or =65 years from 1998 to 2004. First
      degree relatives were eligible if they were aged 45-69 years, living in the UK
      and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of
      1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to
      ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49%
      (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who
      initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided
      a previous PSA result. Among the 170 PSA tests, 10% (17) were > or =4 ng ml(-1)
      and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were
      diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the
      effects of screening, patients with a raised familial risk should be counselled
      in clinic about screening of relatives and data routinely recorded so that the
      effects of screening on high-risk groups can be studied.

PMID- 16434999
TI  - Influence of serotonin receptor 2A His452Tyr polymorphism on brain temporal
      structures: a volumetric MR study.
AB  - Serotonin (5-HT) receptors 2A are expressed in brain regions involved in memory
      and learning processes. Recently, a functional single nucleotide polymorphism in
      the 5-HT2A receptor gene leading to an amino-acid substitution at residue 452
      (His452Tyr) has been involved in memory performance, persons with the rare 452Tyr
      allele showing poorer memory performance compared to His452His subjects. To
      investigate a putative structural effect of this polymorphism on temporal areas
      typically involved in memory processes, we performed voxel-based morphometry
      (VBM) and region-of-interest (ROI) volumetric analysis on high-resolution
      magnetic resonance images in 15 carriers and 61 noncarriers of the 452Tyr allele.
      ROI volumetric analysis showed a significant reduction of the fractional volume
      of the temporal white matter in 452Tyr carriers (0.67+/-0.07 vs 0.73+/-0.08;
      P=0.007). VBM confirmed this finding and in addition showed reduced grey matter
      in the left hippocampus, left inferior temporal gyrus, and bilaterally in the
      middle and superior temporal gyrus. A possible effect on synaptic plasticity or
      neurodevelopment might explain the influence of the His452Tyr polymorphism on
      temporal brain structures, and this might be the basis for poorer memory
      performance in 452Tyr carriers. These findings should be considered preliminary
      and future replication is needed.

PMID- 16435000
TI  - Y-chromosomal STR haplotype analysis reveals surname-associated strata in the
      East-German population.
AB  - In human populations, the correct historical interpretation of a genetic
      structure is often hampered by an almost inherent inability to differentiate
      between ancient and more recent influences upon extant gene pools. One method to
      trace recent population movements is the analysis of surnames, which, at least in
      Central Europe, can be thought of as traits 'linked' to the Y chromosome.
      Illegitimacy, extramarital birth and changes of surnames may have substantially
      obscured this linkage. In order to assess the actual extent of correlation
      between surnames and Y-chromosomal haplotypes in Central Europe, we typed Y
      chromosomal short tandem repeat markers in 419 German males from Halle. These
      individuals were subdivided into three groups according to the origin of their
      respective surname, namely German (G), Slavic (S) or 'Mixed' (M). The
      distribution of the haplotypes was compared by Analysis of Molecular Variance.
      While the M group was indistinguishable from group G (PhiST=-0.0008, P>0.5), a
      highly significant difference (PhiST=0.0277, P<0.001) was observed between the S
      group and the combined G+M group. This surprisingly strong differentiation is
      comparable to that of European populations of much larger geographic and
      linguistic difference. In view of the major migration from Slavic countries into
      Germany in the 19th century, it appears likely that the observed concurrence of
      Slavic surnames and Y chromosomes is of a recent rather than an early origin. Our
      results suggest that surnames may provide a simple means to stratify, and thereby
      to render more efficient, Y-chromosomal analyses of Central Europeans that target
      more ancient events.

PMID- 16435001
TI  - Identification of probable genotyping errors by consideration of haplotypes.
AB  - Undetected genotyping errors pose a problem in genetic epidemiological studies,
      as they may invalidate statistical analysis or reduce its power. Haplotype
      analysis requires an improved standard of the data, because a haplotype can be
      inferred correctly only if the genotypes of all its markers are correct. Here, we
      present a method that identifies probable genotyping errors in trio samples with
      the help of the estimated haplotype frequency distribution of the sample. If the
      likelihood of the most likely haplotype explanation depends strongly on just one
      genotype, in the sense that setting the genotype to be missing leads to a much
      more likely haplotype explanation, this genotype is considered as a potential
      genotyping error. We describe a method that systematically searches the whole
      data set for such potential errors. Based on the haplotype distribution of a real
      data set, we carry out a simulation study to estimate the sensitivity and
      specificity of the method. In addition, we apply our approach to the real data
      set itself. Potentially erroneous genotypes are re-determined via sequencing. The
      results of both the simulation study and of the application to the real data set
      show that a considerable proportion of true genotyping errors is detected and
      that the number of false-positive signals is acceptable. We conclude that it is
      indeed possible to identify probable genotyping errors by considering haplotypes.
      The method described here will be part of the next release of our FAMHAP
      software.

PMID- 16435002
TI  - The impact of the addition of toppings/fillings on the glycaemic response to
      commonly consumed carbohydrate foods.
AB  - OBJECTIVE: To investigate the influence of the addition of various
      toppings/fillings on the glycaemic response to baked potato, pasta and toast.
      DESIGN: Randomised, repeated measures design. SETTING: Oxford, UK. SUBJECTS:
      Forty normal, healthy subjects (11 males and 29 females) were recruited to the
      study. Subjects were staff and students from Oxford Brookes University.
      INTERVENTION: Cheddar cheese, chilli con carne, baked beans and tuna were added
      to baked potatoes, cooked pasta and toast to determine the effect on glycaemic
      response. RESULTS: No significant difference was found among the various toppings
      and baked potato (P=0.06), pasta (P=0.06) and toast (P=0.39). However, the
      addition of toppings to a carbohydrate-rich food had a consistent lowering effect
      on glycaemic index (GI). In particular, the addition of cheddar cheese to potato,
      pasta and toast reduced the GI of the test meal to a value that is considered to
      be low-GI (39, 27 and 35, respectively). This is particularly notable for
      potatoes, which, when eaten alone, had the highest GI value of all the staples.
      CONCLUSIONS: This study has shown that the addition of foodstuffs to the staples
      baked potato, pasta and toast had a consistent lowering effect on the GI value of
      that meal. These findings emphasise the importance of investigating the GI of
      composite meals.

PMID- 16435003
TI  - Odour and taste sensitivity is associated with body weight and extent of
      misreporting of body weight.
AB  - BACKGROUND: Sensory factors are important determinants of appetite and food
      choices but little is known about the relationship between body weight and
      sensory capabilities. OBJECTIVE: To investigate the relationship between measured
      body weights, misreporting of body weight and sensory capabilities. DESIGN: In a
      cross-sectional sensory study, body weight was assessed by measured and self
      reported body weight in healthy men (n=130) and women (n=181). Sensory
      capabilities were assessed as odour detection and identification, and detection
      for salty, sweet, sour and bitter taste. RESULTS: Odour detection, odour
      identification and taste perception scores were lower in subjects with a BMI
      >or=28 kg/m(2) than in subjects with a BMI <28 kg/m(2) in the age group <65 years
      whereas in subjects >or=65 years scores were higher in subjects with a BMI >or=28
      kg/m(2) than in subjects with a BMI <28 kg/m(2) (BMI*age group: P=0.015, 0.053
      and 0.015, respectively). Independent of age, scores were highest in under
      reporters of body weight (P=0.008, 0.001 and 0.017). Differences in taste
      perception could be attributed to sour (P=0.015) and bitter (P=0.026) perception,
      but not to salty or sweet perception. CONCLUSION: Relationship between sensory
      capabilities and body mass is age dependent. Compared to overweight subjects, the
      sensory capabilities of normal weight individuals appear to be higher (<65 years)
      and lower (>or=65 years). At any age, however, subjects who under reported their
      body weight show higher sensory capabilities.

PMID- 16435004
TI  - Recommended screening and preventive practices for long-term survivors after
      hematopoietic cell transplantation: joint recommendations of the European Group
      for Blood and Marrow Transplantation, Center for International Blood and Marrow
      Transplant Research, and the American Society for Blood and Marrow
      Transplantation (EBMT/CIBMTR/ASBMT).
AB  - More than 40,000 hematopoietic cell transplants (HCTs) are performed worldwide
      each year. With improvements in transplant technology, larger numbers of
      transplant recipients survive free of the disease for which they were
      transplanted. However, there are late complications that can cause substantial
      morbidity. Many survivors are no longer under the care of transplant centers and
      many community health-care providers may be unfamiliar with health matters
      relevant to HCT. The Center for International Blood and Marrow Transplant
      Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT),
      and American Society for Blood and Marrow Transplantation (ASBMT) have developed
      these recommendations to offer care providers suggested screening and prevention
      practices for autologous and allogeneic HCT survivors.

PMID- 16435006
TI  - Racial disparities in obstetrical care.

PMID- 16435007
TI  - A comparison of neonatal Gram-negative rod and Gram-positive cocci meningitis.
AB  - OBJECTIVE: Neonatal meningitis is an illness with potentially devastating
      consequences. Early identification of potential risk factors for Gram-negative
      rod (GNR) infections versus Gram-positive cocci (GPC) infection prior to
      obtaining final culture results is of value in order to appropriately guide
      expirical therapy. We sought to compare laboratory and clinical parameters of GNR
      and GPC meningitis in a cohort of term and premature infants. STUDY DESIGN: We
      evaluated lumbar punctures from neonates cared for at 150 neonatal intensive care
      units managed by the Pediatrix Medical Group Inc. We compared cerebrospinal fluid
      (CSF) parameters (white blood cell count, red blood cell count, glucose, and
      protein), demographics, and outcomes between infants with GNR and GPC meningitis.
      CSF cultures positive with coagulase-negative staphylococci were excluded.
      RESULTS: We identified 77 infants with GNR and 86 with GPC meningitis. There were
      no differences in gestational age, birth weight, infant sex, race, or rate of
      Caesarean section. GNR meningitis was more often diagnosed after the third
      postnatal day and was associated with higher white blood cell and red blood cell
      counts. GNR meningitis diagnosed in the first 3 days of life was associated with
      antepartum antibiotic exposure. No difference was noted in either CSF protein or
      glucose levels. After correcting for gestational age, there was no observed
      difference in mortality between infants infected with GNR or GPC. CONCLUSION:
      Compared to GPC meningitis, GNR meningitis was associated with several aspects of
      the clinical history and laboratory findings including older age of presentation,
      antepartum exposure to antibiotics, and elevated CSF white blood cell and red
      blood cell counts.

PMID- 16435008
TI  - Communicating with parents in the NICU.

PMID- 16435009
TI  - Premature rupture of membranes, placenta increta, and hysterectomy in a pregnancy
      following endometrial ablation.
AB  - Endometrial ablation has become a popular method of managing menorrhagia.
      Pregnancy after endometrial ablation has a high rate of complications. We present
      the case of a parous woman with a history of endometrial ablation with preterm
      premature rupture of membranes. Despite the absence of established sonographic
      markers for abnormal placentation, placenta accreta was noted at the time of
      cesarean delivery. In women with history of endometrial ablation, the endometrium
      is not normal and may allow for more aggressive placental invasion or adherence.
      Consequently, the sonographic indices described for evaluating placenta accreta
      may not be present. We believe that placentation in women with prior endometrial
      ablations should be considered extremely high risk for placenta accreta or
      increta and managed accordingly when preparing for delivery.

PMID- 16435011
TI  - A novel triple purge strategy for eliminating chronic myelogenous leukemia (CML)
      cells from autografts.
AB  - Imatinib-refractory chronic myelogenous leukemia (CML) patients can experience
      long-term disease-free survival with myeloablative therapy and allogeneic
      hematopoietic cell transplantation; however, associated complications carry a
      significant risk of mortality. Transplantation of autologous hematopoietic cells
      has a reduced risk of complications, but residual tumor cells in the autograft
      may contribute to relapse. Development of methods for purging tumor cells that do
      not compromise the engraftment potential of the normal hematopoietic cells in the
      autograft has been a long-standing goal. Since primitive CML cells differentiate
      more rapidly in vitro than their normal counterparts and are also preferentially
      killed by mafosfamide and imatinib, we examined the purging effectiveness on
      CD34(+) CML cells using a strategy that combines a brief exposure to imatinib
      (0.5-1.0 microM for 72 h) and then mafosfamide (30-90 microg/ml for 30 min)
      followed by 2 weeks in culture with cytokines (100 ng/ml each of stem cell
      factor, granulocyte colony-stimulating factor and thrombopoietin). Treatment with
      1.0 microM imatinib, 60 microg/ml mafosfamide and 14 days of culture with
      cytokines eliminated BCR-ABL(+) cells from chronic phase CML patient aphereses,
      while preserving normal progenitors. This novel purging strategy may offer a new
      approach to improving the effectiveness of autologous transplantation in imatinib
      refractory CML patients.

PMID- 16435012
TI  - Estrogen as treatment of hemorrhagic cystitis in children and adolescents
      undergoing bone marrow transplantation.
AB  - Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell
      transplantation (HSCT) can cause significant morbidity and mortality. Previous
      reports have suggested a role for estrogen in the control of HC in adult
      patients. Here, we describe the clinical courses of 10 children and adolescents
      treated with estrogen for HC following HSCT. Eight patients (80%) experienced a
      significant improvement in their hematuria following the commencement of therapy,
      with six (60%) undergoing resolution of macroscopic hematuria, without any
      recurrences. The treatment was well tolerated by the majority of patients, with
      only one patient needing to interrupt treatment (hepatotoxicity). We conclude
      that estrogen is well tolerated and often effective, and should be considered as
      an adjunctive treatment option in children and adolescents with HC following
      HSCT.

PMID- 16435013
TI  - Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem
      cell transplantation for advanced pediatric hematologic malignancies.
AB  - We evaluated the efficacy and toxicity of adding 9 Gy of total body irradiation
      (TBI), in three single daily fractions of 3 Gy, to the reduced intensity regimen
      of fludarabine 30 mg/m2 i.v. x 4 days and melphalan 140 mg/m2 i.v. x 1 day in
      advanced pediatric hematologic malignancies. Twenty-two acute lymphoblastic
      leukemia (ALL), six acute myeloid leukemia (AML), and one non-Hodgkin lymphoma
      patients were transplanted. Of these, 13 were beyond second remission, and five
      had prior hematopoietic stem cell transplant (HSCT). Twenty-one donors were
      unrelated, of which 19 were from cord blood (CB) units. Three of the eight
      related donors were genotypically disparate. Oral mucositis and diarrhea were the
      most common toxicities. Twenty-seven patients achieved neutrophil engraftment
      (median 16 days), and 23 had platelet engraftment (median 42 days). One patient
      had primary graft failure. Seven patients died of non-relapse causes in the first
      100 days. With a median follow-up of 52 months, seven of 22 ALL, five of six AML,
      and one of one lymphoma patients are alive and in remission. The regimen of TBI,
      fludarabine, and melphalan allows the engraftment of allogeneic hematopoietic
      stem cells (including mismatched CB). It was fairly well tolerated in pediatric
      patients, even for second transplants. Its efficacy requires further evaluation.

PMID- 16435014
TI  - Genetic polymorphisms in the genes encoding human interleukin-7 receptor-alpha:
      prognostic significance in allogeneic stem cell transplantation.
AB  - Interleukin-7 (IL-7) is essential for T-cell development in the thymus and for
      the maintenance of peripheral T cells. IL-7 signals through IL-7R, that consists
      of the gammac-chain and an alpha-chain. Sequencing of IL-7Ralpha has revealed the
      existence of four single nucleotide polymorphisms (SNPs) (+510C/T, +1237 A/G,
      2087T/C and +3110A/G), which all give rise to amino-acid substitutions. The aim
      of the present investigation was to evaluate the significance of IL-7Ralpha SNPs
      for the outcome in allogeneic stem cell transplantation (SCT). IL-7Ralpha
      polymorphisms were determined in 195 recipient and donor pairs from either
      matched sibling donors or matched unrelated donors (MUD). Genotyping of 173
      normal controls was performed in parallel. In MUD transplants, the +1237 genotype
      of the donor was associated with survival after SCT, the mortality being highest
      and intermediate for the GG and AG genotypes, respectively (P = 0.023). This
      pattern was more pronounced with respect to treatment-related mortality (P =
      0.003), while IL-7Ralpha genotypes were unrelated to the risk of relapse of
      leukaemia. The IL-7Ralpha +1237 genotype of the recipient and the genotypes of
      the other three polymorphisms, were not significantly associated with the outcome
      of SCT. These findings suggest that the IL-7Ralpha polymorphisms may be of
      importance for treatment-related mortality after SCT.

PMID- 16435015
TI  - Patterns of C-reactive protein release following allogeneic stem cell
      transplantation are correlated with leukemic relapse.
AB  - The C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes,
      and is a reliable marker of systemic inflammation, which is relevant to the
      release of the proinflammatory cytokines. The value of monitoring the CRP levels
      after stem cell transplantation (SCT) can identify patients at risk of treatment
      related complications and mortality. Inflammatory cytokines facilitate donor T
      cell activation via antigen presenting cells immediately after SCT. This study
      examined the relationship between the post-SCT CRP levels and a leukemic relapse.
      Fifty-four consecutively transplanted patients who relapsed after the allogeneic
      SCT were compared with nonrelapsing patients. The serum CRP levels were measured
      on day 0 and every 7 days thereafter until 4 weeks after the SCT. The mean CRP
      levels throughout the early post-SCT episode were significantly lower in the
      relapsing patients than in those who did not experience relapse (mean+/-s.e.:
      26.8 +/- 6.3 vs 65.3 +/- 9.4 for first week, P = 0.001; 23.9 +/- 3.8 vs 44.6 +/-
      6.6 for second week, P = 0.008). Univariate analysis showed that the CRP level on
      the first and second week, and graft-versus-host disease were significantly
      associated with a relapse. Multivariate analysis showed that the CRP level on the
      first week was the strongest independent variable predicting the risk of a
      relapse after SCT (P = 0.04). These results indicate that the serum CRP levels
      early after allogeneic SCT might display the graft-versus-leukemia (GvL) effect.
      CRP is a surrogate of the proinflammatory cytokine release that was not measured
      in this study. The GvL effect appears to be efficiently strengthened by the high
      CRP levels that may be reflecting T-cell activation.

PMID- 16435016
TI  - Hematopoietic stem cell transplantation for 30 patients with primary
      immunodeficiency diseases: 20 years experience of a single team.
AB  - We retrospectively analyzed our results of 30 patients with three distinctive
      primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID,
      n = 11), Wiskott-Aldrich syndrome (WAS, n = 11) and X-linked hyper-immunoglobulin
      M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the
      past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T
      cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched
      related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord
      blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing
      infections with or without organ damages before HSCT. Conditioning regimen and
      GVHD prophylaxis were determined according to disease, donor and pretransplant
      status. Although one of eight patients transplanted with TCD is alive with full
      engraftment, the other seven died. On the other hand, 18 of 22 patients
      transplanted without TCD are alive and well, including six of eight transplanted
      from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19
      survivors did not require Ig supplementation after HSCT. These results indicate
      that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD
      SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy
      and monitoring for various pathogens are important for the successful HSCT.

PMID- 16435017
TI  - Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen
      suitable for allogeneic transplantation that maintains the graft versus
      malignancy effect.
AB  - Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation
      allows stable donor cell engraftment with the maintenance of a graft versus
      malignancy effect. Many different regimens exist employing various combinations
      of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T
      cell depleted RIC regimens in 56 patients with haematological malignancies.
      Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25
      mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100
      mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and
      CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed
      >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of
      patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day
      mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was
      0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a
      median of 19 months post transplant (range 3-38 months). We have shown that
      patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with
      CyA/MTX as post transplant immunosuppression can achieve good disease control
      with an acceptable level of toxicity. Further studies are required to confirm
      these findings.

PMID- 16435018
TI  - Incidence of Clostridium difficile-associated diarrhea before and after
      autologous peripheral blood stem cell transplantation for lymphoma and multiple
      myeloma.
AB  - Diarrhea is a major cause of morbidity and discomfort for patients undergoing
      high-dose chemotherapy and autologous peripheral blood stem cell transplantation
      (APBSCT). There are multiple causes of diarrhea in patients undergoing
      transplantation including antineoplastic chemotherapy, antimicrobials and
      infection, including Clostridium difficile as the most common pathogen involved.
      The purpose of this study was to determine the incidence of C. difficile
      associated diarrhea (CDAD) 1 week before and 30 days after APBSCT, and to
      identify risk factors for the development of CDAD including diagnosis. Two
      hundred and forty-two patients underwent APBSCT for multiple myeloma and lymphoma
      between October 1996 and October 2001 in two teaching hospitals. Diarrhea was
      reported in 157 (64.9%) subjects. One hundred and thirty-five out of the 157
      subjects were tested for the presence of C. difficile toxin A. These subjects
      constitute the study group. The incidence of CDAD was 15%. Two thirds of the
      patients who developed CDAD had multiple myeloma and one third had lymphoma; this
      difference did not attain statistical significance. The use of cephalosporins (P
      = 0.03) and the use of intravenous vancomycin (P = 0.02) were the only identified
      risk factors associated with the development of CDAD. Patients treated with
      paclitaxel as part of the mobilization regimen had a lower incidence of CDAD than
      patients who received hematopoietic growth factor only (P = 0.01).

PMID- 16435019
TI  - Weight loss and reduced body mass index: a critical issue in children with
      multiorgan chronic graft-versus-host disease.
AB  - Weight loss and malnutrition are major problems in patients with chronic graft
      versus-host disease (GVHD). In adults, low body mass index (BMI) is a predictor
      for mortality; however, weight loss and BMI have not been studied in pediatric
      chronic GVHD. A retrospective study on 18 children with extensive chronic GVHD
      was completed. Median age at SCT was 12.3 (range 0.6-23) years; age at chronic
      GVHD diagnosis was 12.5 (1-23) years. Patients with multiorgan involvement had a
      mean maximal decrease in BMI of 20.9% and most dropped below 10th percentile in
      expected weight-for-age. This change in BMI not only indicates a significant
      decrease in weight but often a plateau in stature. In contrast, patients with one
      organ system involved had a mean maximal decrease in BMI of 5% and did not fall
      below 10th percentile. All patients with multiorgan involvement required salvage
      therapy beyond steroids and CSA. Three patients died due to complications of
      chronic GVHD. Weight loss and malnutrition (as reflected by a decrease in BMI)
      are clinically significant issues in children with multisystem chronic GVHD.
      Weight loss is likely another systemic manifestation of the disease and may
      contribute, along with other factors such as increased immunosuppression and
      infection, to increased mortality in this group.

PMID- 16435020
TI  - Clonal cytogenetic changes and myeloma relapse after reduced intensity
      conditioning allogeneic transplantation.
AB  - To identify a correlation between metaphase cytogenetics and relapse after
      reduced intensity conditioning (RIC) allotransplant for patients with multiple
      myeloma, data on 60 patients (median age 52) who received grafts from a sibling
      (n = 49) or unrelated donor (n = 11) were analyzed. Fifty-three patients (88%)
      showed chromosomal abnormalities (CA) before the allotransplant, including 42
      with abnormalities involving 13q (CA13). Twenty-two patients (41%) relapsed post
      allotransplant at a median of 165 days. Of these, 11 patients showed abnormal
      cytogenetics at the time of post-allotransplant relapse at a median of 167 days.
      Of 54 patients who developed graft-versus-host disease, relapse occurred in 19 of
      48 patients (43%) with CA present before RCI allotransplant, versus 1 of 6
      without CA (17%) (P = 0.06). Loss of CA before RIC allotransplant and disease
      status > PR after RIC allotransplant were significantly associated with a lower
      risk of post-allotransplant relapse with cytogenetic abnormalities; 5.2 vs 36%,
      and 18 vs 53%, (both P < 0.05), respectively. The current data suggests that
      myeloma associated with persistent clonal cytogenetic abnormalities is an entity
      which most likely escapes the effects of a graft versus myeloma activity, maybe
      because of acquisition of resistance to immunologic manipulations.

PMID- 16435021
TI  - Patients' understanding of disease status and treatment plan at initial
      hematopoietic stem cell transplantation consultation.
AB  - Patients referred for hematopoietic stem cell transplantation (HSCT) often have
      knowledge deficits about their disease and overestimate their prognosis making it
      difficult initially to discuss potentially life-threatening transplant options.
      To determine patients' understanding of their disease and the adequacy of a 3-h
      consultation at our center, we developed a survey that measured perceived
      knowledge deficits of disease, prognosis, and emotional status before and after
      their initial consultation. Ninety nine consecutive eligible patients completed
      the survey. Although 76.7% claimed adequate information about their disease pre
      HCST visit, 51.5 and 41.4% respectively lacked knowledge about their 1-year
      prognosis with and without any therapy. After the visit, 66.7% of the patients
      had obtained enough information to make an informed decision regarding HSCT
      versus 23.2% pre-visit, and a significant reduction in the need for further
      information was reported by 53.5% of patients (P<0.001). Patients were not
      overwhelmed or confused by the visit and there was a small but significant
      decrease in negative affect. Measures to increase patients understanding of their
      disease and its prognosis pre-HSCT consultation visit are warranted; however, a 3
      h consultation visit provides the majority of patients with sufficient
      information to make an informed decision about the risk/benefit ratio of HSCT.

PMID- 16435022
TI  - Susceptibility to JRA/JIA: complementing general autoimmune and arthritis traits.
AB  - Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis
      (JIA), includes the most common chronic autoimmune arthropathies of childhood.
      These two nomenclatures for classification include components representing the
      major subclasses of disease. The chromosomal regions and the genes involved in
      these complex genetic traits are being elucidated, with findings often specific
      for a particular disease subtype. With the advent of new SNP technologies,
      progress is being made at an ever-increasing pace. This review discusses the
      difficulties of deciphering the genetic components in complex disorders, while
      demonstrating the similarities that JRA shares with other autoimmune disorders.
      Particular emphasis has been placed on positive findings either for candidate
      genes that have been replicated independently in JRA/JIA, or findings in JRA for
      which consistent results have been reported in other forms of autoimmunity.

PMID- 16435023
TI  - Involvement of antibody production quantitative trait loci in the susceptibility
      to pristane-induced arthritis in the mouse.
AB  - Mice obtained by bidirectional selective breeding for high (HIII) or low (LIII)
      antibody (Ab) production are resistant or extremely susceptible to pristane
      induced arthritis (PIA), respectively. Several quantitative trait loci regulating
      Ab production (Ab QTL) have been mapped in these lines, which were used to
      investigate the influence of these Ab QTL in PIA. Parental HIII and LIII mice and
      their F1 and F2 intercrosses were injected twice with pristane, and arthritis was
      observed for 200 days. In LIII mice PIA was more severe and incidence was 100% at
      day 105, while F1 and F2 mice showed intermediate values. HIII mice were totally
      resistant. Microsatellite polymorphisms of Ab QTL were analysed and D3Mit100
      alleles cosegregated significantly with PIA incidence, severity and onset in F2
      intercross mice, while the other four markers showed suggestive values. Results
      indicate colocalization of QTL for Ab production and PIA susceptibility.
      Moreover, the different cytokine and IgG isotype profiles observed in HIII and
      LIII lines after PIA induction are useful to candidate genes endowed with the
      regulation of the Ab production and arthritis phenotypes.

PMID- 16435024
TI  - Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children.
AB  - Human beta-defensin (HBD)-1 is constitutively expressed in the airway, and hBD-1
      plays crucial roles in innate immunity against respiratory pathogens. Asthma was
      associated with DEFB1 polymorphisms in Caucasians. This study investigates
      whether three single nucleotide polymorphisms (SNPs) in 5'-untranslated region of
      DEFB1 are associated with asthma phenotypes in Chinese children. Subjects aged 5
      18 years were recruited from general pediatric clinics. Plasma IgE concentrations
      were measured by immunoassays. DEFB1 SNPs were characterized by restriction
      fragment length polymorphism. In all, 305 asthmatics and 156 controls were
      recruited. For asthma diagnosis, atopy and plasma total IgE, higher percentages
      of subjects with these outcomes had the minor alleles -20A and -52G (P = 0.041
      0.0002). For log-transformed total IgE, the covariate was positive and
      significant for G-20A under recessive model (P = 0.001) and for G-52A under both
      recessive and codominant models (P = 0.008 and 0.035). The recessive model
      covariate was also positive and significant (P = 0.020) for C-44G on peripheral
      blood eosinophil count. The GCA haplotype of DEFB1 was significantly associated
      with asthma (odds ratio (95% confidence interval): 1.64 (1.05-2.57); P = 0.029).
      These results suggest that DEFB1 is a candidate gene for asthma and atopy in
      children.

PMID- 16435025
TI  - Arnold Pavlik (1902-62): an autobiography.
AB  - Professor Arnold Pavlik, a Czech orthopaedic surgeon, became famous mainly for
      the development of a functional, active method of treating developmental
      dysplasia of the hip, in his time called congenital dislocation of the hip. A
      translation is presented of the autobiography Pavlik prepared to achieve his
      doctorate in medical sciences, but which his early death in February 1962 denied
      him.

PMID- 16435026
TI  - Sir Frederick Treves (1853-1923) Dorchester cemetery, Dorset.

PMID- 16435027
TI  - Undercurrents on the Nile: the life of Dr John B Christopherson (1868-1955).
AB  - In the early 1900s, Dr J B Christopherson was one of a small number of British
      physicians who found their way to Khartoum, the capital of Sudan. The city had
      been laid waste by the battles of the legendary Mahdi and the armies of the
      British. Sudan was now considered part of an Anglo-Egyptian Condominium.
      Christopherson became, partly by force of circumstance, a specialist in tropical
      medicine. His principal claim to fame, briefly contested for priority, was the
      treatment of bilharzia (schistosomiasis) by injections of antimonium tartaratum
      (tartar emetic). The paper sketches Christopherson's turbulent life in Africa and
      identifies some important events in the life of this man whose energies were
      directed not only to treating patients and building a medical department in the
      desert, but also to fighting a rearguard action to preserve his reputation.

PMID- 16435028
TI  - Leading a double life in 17th-century Oxford: Ralph Bathurst (1620-1704),
      physician-physiologist and cleric.
AB  - Ralph Bathurst spent most of his working life in Trinity College, Oxford.
      Strongly influenced by William Harvey, he was a friend and colleague of Thomas
      Willis, Robert Boyle and many other eminent experimentalists. His intended career
      as an Anglican priest and theologian was frustrated during the Commonwealth.
      Instead, he trained as a physician and practised in Abingdon in Berkshire and in
      the Navy. His examination papers for the degrees of Bachelor and Doctor of
      Medicine survived and were printed many years after his death. This paper,
      summarizing the three Latin lectures on respiration given for his doctoral degree
      in 1654, throws light on the physiological research carried out in Oxford at that
      time. The lectures included clinical observations, the results of experiments
      performed by himself and others, and speculations on the chemistry of air in the
      era before Joseph Priestley.

PMID- 16435029
TI  - Daniel Lambert (1770-1809).

PMID- 16435030
TI  - Post-Peninsular War activities of Sir James McGrigor (1771-1858), Wellington's
      Director-General of the Army Medical Department.
AB  - James McGrigor (1771-1858) entered the Army Medical Department in September 1793,
      when he purchased a Surgeoncy in De Burgh's regiment. He transferred to the Blues
      (the Royal Horse Guards) in 1804 and shortly afterwards his organizational skills
      were recognized by the Duke of York. In 1811, he recommended McGrigor to
      Wellington, who commanded the British Forces in the Peninsula, and McGrigor
      joined Wellington in January 1812. As a result of his outstanding achievements
      during the Peninsular War, McGrigor was knighted in 1814. He later played a
      critical role in the post-Peninsular War Army by elevating the academic standard
      of the intake of medical officers as well as improving the standard of those who
      wished to gain promotion in the service. He established an extensive Anatomy,
      Pathology and Natural History Museum and the reference library at Fort Pitt at
      Chatham in Kent. He retired at the beginning of 1851, and died in London in April
      1858, aged 87. In 1863, the museum collections were moved initially to the Army
      Medical School at Netley. At a later date these collections were dispersed and
      their present whereabouts are unknown. A significant proportion of his library is
      presently located in the Contemporary Medical Archives Centre on permanent loan
      in the library of the Wellcome Institute for the History of Medicine.

PMID- 16435031
TI  - Richard Caton (1842-1926): pioneer electrophysiologist and cardiologist.
AB  - Richard Caton is recognized as the discoverer of the waves of electrical
      potential which today form the basis of electroencephalography. He reported his
      finding in three communications, two in the British Medical Journal and one to
      the Ninth International Congress of Medicine at Washington, DC. After defending
      his priority in having made this discovery, he did no further work on the brain:
      his family and colleagues were unaware of his discovery for many years after his
      death. This was possible partly because of many other things that he did in his
      long life but also because, in his later years, he took deliberate steps to hide
      the fact that he had worked on the brain. The most important of these other
      activities was a practical study of the treatment of rheumatic heart disease. The
      basis of his treatment--complete rest in bed--is still in use today.

PMID- 16435032
TI  - Dr James Currie (1756-1805): Liverpool physician, campaigner, hydrotherapist and
      man of letters.
AB  - James Currie was born and educated in Scotland but spent most of his professional
      life in Liverpool, where, as physician to the Liverpool Infirmary, he campaigned
      against the unsanitary living conditions in the rapidly growing port. He was an
      early advocate of water cures for fever and other maladies, on which subject he
      carried out experiments and published a seminal work. He was a pioneer in the use
      of the clinical thermometer. He was also an early advocate of the abolition of
      slavery and a man with literary and scientific interests, which brought him into
      contact with many of his most distinguished contemporaries. These included
      Erasmus Darwin (1731-1802), William Wilberforce (1759-1833), Sir Walter Scott
      (1771-1832), Sir Joseph Banks (1743-1820) and Robert Burns (1759-96), of whose
      poetry Currie was the first editor. He died in August 1805 at Sidmouth in Devon,
      whose parish church carries his memorial.

PMID- 16435033
TI  - Robert Robertson, FRS (1742-1829): physician to the Royal Hospital, Greenwich,
      18th-century authority on 'fever', and early practitioner in care of the elderly.
AB  - Robert Robertson was born in Scotland and trained to be a surgeon. In 1760, he
      served briefly on a whaling ship and then entered the Royal Navy. He subsequently
      had many postings, several of them to the tropics. He recorded his observations
      on fevers, scurvy and other illnesses. After 23 years of active service, he
      retired to private practice in Hampshire. However, later he rejoined the service
      and was appointed physician to the Royal Hospital, Greenwich, where later he was
      made a Director. During this period, he addressed the problems of illness after
      the days of active service. Robertson was thus an early practitioner in the care
      of the elderly. He retired in 1807 and died at Greenwich at the age of 87.

PMID- 16435034
TI  - Sir William Dunn (1833-1912): the man, his trust and his legacy to science and
      medicine.
AB  - William Dunn had no direct connections with medicine. He belonged to that
      Victorian generation of Scottish pioneers who went overseas to make their
      fortunes and, yet, devoted their money to numerous charitable purposes, mainly at
      home in the UK. His family origins were modest; born in Paisley, near Glasgow on
      1 September 1833, he died in 1912 with an estate valued at 1.3 million pounds
      sterling. His fortune was made from a large worldwide trading empire with roots
      in South Africa, where he emigrated as a young man of 19--but later controlled
      from London. In his will, dated 4 November 1908, the key clause was 'to advance
      the cause of Christianity, to benefit children and young people, to support
      hospitals and alleviate human suffering, to encourage education and promote
      emigration'. After making provision for about half the total, he left the
      remainder in the hands of trustees. They allotted about 120 small sums to
      hospitals, nursing homes, orphanages and like institutions, but then decided that
      larger projects would be more likely to be permanent memorials to Sir William.
      After consulting the President of the Royal Society, Sir William Hardy, and the
      Secretary of the Medical Research Committee, Sir Walter Fletcher, the trustees
      gave 210,000 pounds sterling in 1920 to Sir Frederick Gowland Hopkins in
      biochemistry in Cambridge and 100,000 pounds sterling in 1922 to Professor
      Georges Dreyer in pathology in Oxford. Between them, these two laboratories have
      'spawned' nine Nobel Prize winners. The 'alleviation of human suffering' achieved
      would surely have pleased Sir William and his trustees.

PMID- 16435035
TI  - The Baron Doctor Cornelius Ver Heyden De Lancey (1889-1984): dental surgeon,
      doctor and lawyer.
AB  - The Baron Doctor Cornelius Ver Heyden De Lancey is one of the few persons to
      qualify in dental surgery, medicine and the law. He was an author and art
      historian and spoke five languages and he was an important benefactor for
      students and practitioners of the three professions and for others through the De
      Lancey and De La Hanty Foundation Limited, which he established in 1971. This
      paper follows the Baron's professional progress from his birth in Holland to his
      death in Jersey. He gained a plethora of qualifications. His professional
      activities explain why certain organizations gained from his philanthropy.

PMID- 16435036
TI  - David Pyke (1921-2001).

PMID- 16435037
TI  - The influence of Israel Health Insurance Law on the Negev Bedouin population--a
      survey study.
AB  - The extension of universal health service insurance to national populations is a
      relatively new phenomenon. Since 1995, the Israeli National Health Insurance Law
      (NHIL) has provided universal health services to every resident, but the effect
      of this law on health and health services among minorities has not been examined
      sufficiently. The goals of this study were to track some of the first changes
      engendered by the NHIL among the Negev Bedouin Arabs to examine the effects of
      universal health care services. Methods included analysis of historical and
      health policy documents, three field appraisals of health care services (1994,
      1995, 1999), a region-wide interview survey of Negev Bedouins (1997), and key
      informant interviews. For the interview survey, a sample of 515 households was
      chosen from different Bedouin localities representing major sedentarization
      stages. Results showed that prior to the NHIL, a substantial proportion of the
      Negev Bedouins were uninsured with limited, locally available health service.
      Since 1995, health services, particularly primary care clinics and health
      manpower, have dramatically expanded. The initial expansion appears to have been
      a marketing ploy, but real improvements have occurred. There was a high level of
      health service utilization among the Bedouins in the Negev, especially private
      medical services, hospitals, and night ambulatory medical services. The NHIL
      brought change to the structure of health services in Israel, namely the
      institution of a national health system based on proportional allocation of
      resources (based on size and age) and open competition in the provision of
      quality health care. The expansion of the pool of potential members engendered by
      the new universal coverage had profound effects on the Health Funds' attitudes
      towards Negev Bedouins. In addition, real consumer choice was introduced for the
      first time. Although all the health care needs of this rapidly growing population
      have yet to be met fully, the assurances under the Law and the new level of
      competition promise a higher level of service in the future.

PMID- 16435038
TI  - Prevalence of diabetes and cardiovascular comorbidity in the Canadian Community
      Health Survey 2002-2003.
AB  - Diabetes mellitus is a major risk factor for heart disease (heart attack, angina,
      and heart failure), stroke, and hypertension, which shorten the average life
      expectancy. The main objective of this study was to describe the prevalence of
      heart disease, hypertension, and stroke among Canadians with diabetes compared to
      those without diabetes in the Canadian general population aged 12 years and over.
      It also estimated the strength of association between diabetes, heart disease,
      hypertension, and other factors such as age, gender, cigarette smoking, alcohol
      drinking, education status, body mass index (BMI), and other socioeconomic
      factors. Descriptive statistics were used initially to estimate the prevalence of
      related comorbidities by age and gender. Logistic regression was then employed to
      determine the potential strength of association between various effects. Data
      included 127,610 individuals who participated in the 2.1 cycles of the Canadian
      Community Health Survey (CCHS) in 2002-2003. The prevalence of self-reported
      hypertension, heart disease, and stroke among individuals with diabetes were
      51.9, 21.7, and 4.8%, respectively. By comparison, prevalence among those without
      diabetes was 12.7, 4.2, and 0.9%. Adjusted Odds Ratios (OR) were 4.15, 5.04, and
      6.75 for males', and 4.10, 5.29, and 4.56 for females' hypertension, heart
      disease, and stroke, respectively. Lower income (OR from 1.27-1.94) and lower
      education (OR from 1.23-1.86) were independently associated with a high
      prevalence of hypertension, heart disease, and stroke among diabetics. Alcohol
      consumption (OR from 1.06-1.38), high BMI (OR from 1.17-1.40), physical
      inactivity (OR from 1.21-2.45), ethnicity, and immigration status were also
      strongly associated with hypertension, heart disease, and stroke. The adjusted
      prevalence of hypertension, heart disease, and stroke in the CCHS-2003 health
      survey in Canada was significantly higher among those with diabetes compared to
      those without. Other factors such as age, gender, BMI, lifestyle, family incomes,
      physical activity levels, and socioeconomic status also affected the strength of
      association between diabetes and resulting comorbidities.

PMID- 16435039
TI  - Quality of life and events in the first year of life. Results from the
      prospective Copenhagen Birth Cohort 1959-61.
AB  - The objective of this paper was to explore the association between diverse
      factors occurring during the first year of a child's life and the quality of life
      later as an adult. The design was a prospective cohort study based on material
      from the Copenhagen Birth Cohort 1959-61 with 7,222 participants and two sets of
      questionnaires used: one by a physician during the child's first year and one by
      the "adult child" 31-33 years later. The results showed that a mother's attitude
      towards her pregnancy, unsuccessful abortions, and/or institutionalization left a
      permanent trace on the child, since these children, as adults, have a quality of
      life 3% below the average. Meningitis during the first year of life resulted in a
      quality of life 11.7% below the average, while other illnesses or accidents did
      not have an effect. The largest associations were found with psychomotor
      development, where "walking with support" showed a difference of 14.2% in overall
      quality of life between the fastest and slowest group. Generally, diet is not
      correlated with quality of life, however, we find a small, but essential,
      correlation between the quality of life of the adult and the early cessation of
      suckling (4%). Full-time institutionalization during the first year of life
      showed a connection with the quality of life of the adult (7.1%). It is concluded
      that our quality of life, health and ability as adults are primarily determined
      by what we ourselves choose to do with our lives as young people and as adults-
      and only to a marginal degree determined by factors related to our background.
      This suggests that we as adults have a great freedom to achieve a good life
      despite our experiences in the beginning of life.

PMID- 16435040
TI  - Androgen excess disorders in women: the severe insulin-resistant hyperandrogenic
      syndrome, HAIR-AN.
AB  - HAIR-AN syndrome (hyperandrogenism, insulin resistance, acanthosis nigricans) is
      a subset of the polycystic ovary syndrome, where the patients demonstrate severe
      insulin resistance. It is theorized that both genetic and environmental factors,
      such as obesity, give rise to the development of HAIR-AN. Diagnosis is primarily
      clinical, with laboratory values lending further support. Treatment is aimed at
      decreasing insulin resistance, regulating ovulation, and decreasing acne,
      acanthosis nigricans, and hirsutism.

PMID- 16435041
TI  - The biomolecular and ultrastructural basis of epidermolysis bullosa.
AB  - Transmission electron microscopy, immunoelectron microscopy, immunofluorescence
      and antigenic mapping have improved our understanding of the dermo-epidermal
      junction. We have reviewed some ultrastructural and biomolecular aspects related
      to the dermo-epidermal junction. In part, they are implicated in the pathogenesis
      of a group of hereditary disorders characterized by skin fragility, collectively
      known as epidermolysis bullosa (EB). These disorders could benefit in the near
      future from a gene therapy approach but at present genetic counseling, prenatal
      diagnosis and conservative treatment measures offer little real benefit to
      patients.

PMID- 16435042
TI  - Vitiligo.
AB  - Vitiligo represents a selective destruction of the melanocytes. It is a
      relatively common, probably autoimmune disorder that affects people of all
      backgrounds and both genders. No particular group seems to be preferentially
      affected. Half of vitiligo patients have an onset before the age of 18 years. In
      regions where leprosy is endemic, individuals with vitiligo are often stigmatized
      due to similarities in appearance between the two diseases. We will review this
      important subject, emphasizing the latest therapeutic advances.

PMID- 16435043
TI  - Retrospective and prospective evaluation of the Amplicor HPV test for detection
      of 13 high-risk human papillomavirus genotypes on 862 clinical samples.
AB  - BACKGROUND: Persistent infection with a subgroup of at least 15 high-risk human
      papillomavirus (HPV) genotypes is considered as a necessary although insufficient
      etiological factor in the development of cervical carcinoma. As a consequence,
      HPV testing has recently become an important part of the cervical carcinoma
      screening and detection algorithms. AIM OF THE STUDY: To evaluate the analytical
      performance of a recently developed polymerase chain reaction (PCR)-based
      Amplicor HPV test (Roche Molecular Systems) in comparison with the Hybrid Capture
      2 HPV DNA test (hc2) (Digene Corporation) for the detection of 13 high-risk HPV
      genotypes. Inhouse consensus PGMY09/PGMY11 and CPI/IIg PCRs targeting two
      different HPV genes coupled with HPV genotyping were used as an HPV internal
      reference standard. MATERIALS AND METHODS: In the retrospective evaluation, 550
      cervical scrape specimens with previously established HPV status were included.
      Additionally, 312 cervical scrape specimens were tested prospectively for the
      presence of 13 high-risk HPV genotypes by both hc2 and Amplicor HPV test.
      RESULTS: In the retrospective evaluation, the Amplicor HPV test results agreed
      almost completely with the HPV internal reference standard results. In the
      prospective evaluation performed on 312 samples, the concordant Amplicor and hc2
      results were obtained in 85.9% of samples tested. CONCLUSION: In our hands, the
      Amplicor HPV test demonstrated high analytical sensitivity and specificity. The
      higher analytical specificity of Amplicor in comparison to that of hc2 can be
      considered clinically useful. Prospective studies with clinical endpoints are
      urgently needed to assess the clinical utility of the higher analytical
      sensitivity of the Amplicor HPV test for primary HPV screening and triaging
      patients with ASC-US.

PMID- 16435044
TI  - Mycetoma: retrospective study of 13 cases in Tunisia.
AB  - Mycetomas are inflammatory pseudotumors of chronic and progressive evolution, of
      fungal (Eumycetoma), or bacterial (Actinomycetoma) origin. We conducted a
      retrospective study of patients who have been consulted for mycetoma over a
      period of 28 years. Thirteen cases of mycetomas were collected during the 28-year
      period, 10 patients were of rural origin. The lesions were localized on the foot
      in all instances. There was no male predominance. Histopathological examination
      confirmed mycetoma in all 13 cases and the determination of the infectious agent
      in 9 cases: 4 actinomycotic and 5 fungal. Microbiological examination identified
      the species in 7 cases. Bone involvement was found in 10 cases. Eumycetomas were
      treated by ketoconazole. The other cases were treated as actinomycetomas by
      antibiotics. The antibiotic treatment was associated with surgical excision in 4
      cases and with amputation in 1 case. Mycetomas are rare in Tunisia, and only
      observed sporadically, for this reason the diagnosis is usually late, with severe
      functional, psychological, and socioeconomic consequences.

PMID- 16435045
TI  - Eyebrow colour in diabetics.
AB  - BACKGROUND: Hair colour may be affected by a metabolic disease. Systematic
      investigations in diabetics are missing. OBJECTIVE: A clinical study was
      performed to evaluate whether dark colour of eyebrows in greying males is
      associated with diabetes or not. SETTING: Academic teaching hospital, inpatient
      and outpatient department. METHODS: In an uncontrolled analysis two groups of
      male patients between 50 to 70 years of age were investigated for evidence of
      diabetes mellitus. Inclusion criteria were original scalp hair colour brown to
      black with more than 50% greying hair, no chemotherapy, hormone (except insulin)
      or interferon treatment, current or previous, no artificial colouring of hair,
      and absence of total alopecia. Group A consisted of 50 males with dark eyebrow
      colour, group B of 50 males with greying of eyebrows. A careful medical history
      and clinical examination was performed. In patients without known diabetes, blood
      sugar levels (profile during the day) and HbA1c were evaluated. RESULTS: In group
      A 38 of 50 patients (76%) were diabetics type II. The mean duration of diabetes
      was 3.4 years (SD 6.8 years; range 1 year to 31 years). Six patients were
      diagnosed as having diabetes for the first time. In group B 9 of 50 patients
      (18%) were diabetics, two of type I and 7 of type II. One patient with a newly
      detected diabetes type II was seen. The mean duration of diabetes was 4.1 years
      (SD 7.6 years; range: 1 year to 39 years). The difference in diabetes frequency
      is statistically highly significant (two-sided t-test: p<0.0001). Odds ratios
      (OR) for diabetes are higher in greying males with dark eyebrows (OR 3.17) vs.
      those with greying eyebrows and scalp hair (OR 0.19) in this age group.
      CONCLUSIONS: In male diabetics at the age of 50 years or more greying of the
      eyebrows seems to be inhibited or delayed. The presence of dark eyebrows with
      greying scalp hair in males might be a clinical sign for patients at risk of
      diabetes type II.

PMID- 16435046
TI  - Necrolytic migratory erythema associated with hyperglucagonemia and
      neuroendocrine hepatic tumors.
AB  - We present a 61-year-old man with a 2-year history of persistent disseminated,
      psoriasiform annular pruritic lesions, acrodermatitis, weight loss, anemia and
      diabetes. Histopathology of the affected skin showed nonspecific subacute
      psoriasiform dermatitis. The computed tomographic scan of the abdomen revealed
      multiple hepatic tumors. Histopathological examination of ultrasound-guided
      needle biopsy from a hepatic lesion demonstrated a neuroendocrine tumor.
      Somatostatin-receptor scintigraphy with radio-labelled octreotide confirmed the
      likelihood of the neuroendocrine nature of the hepatic tumors and excluded the
      presence of other such lesions throughout the rest of the body, including the
      pancreas. The serum glucagon level was markedly increased. The diagnosis of
      necrolytic migratory erythema associated with hyperglucagonemia and
      neuroendocrine hepatic tumors was made and therapy with the long-acting
      somatostatin analogue octreotide was started. The skin changes resolved after the
      initiation of therapy, but no improvement of other symptoms was observed. Having
      reached the final stage of the disease, which was further complicated by
      congestive heart failure, the patient died one year later. As no autopsy was
      performed, we were unable to establish whether the hepatic tumors represented a
      metastatic process of previously undetected pancreatic glucagonoma or if they
      were extra-pancreatic glucagon-secreting tumors. The correct diagnosis of
      necrolytic migratory erythema is important, since it might be the clue for early
      detection of glucagonoma or of extra-pancreatic glucagon-secreting tumors.

PMID- 16435047
TI  - Editors of dermatological journals.

PMID- 16435048
TI  - The liver in surgery.

PMID- 16435049
TI  - Tips from the experts: local advice for local practice.

PMID- 16435051
TI  - The skin and joint manifestations of diabetes mellitus: superficial clues to
      deeper issues.

PMID- 16435052
TI  - Presentation of drug-induced liver injury in Singapore.
AB  - INTRODUCTION: Drug-induced liver injury (DILI) is an important clinical problem.
      However, although traditional Chinese medicines (TCM) are widely consumed in
      Asia, most cases of TCM-DILI are reported as case reports or case series. We
      aimed to evaluate the clinical course of DILI at an Asian tertiary liver centre.
      METHODS: All patients with DILI seen by one hepatologist from July 2003 to June
      2004 at a local liver centre were prospectively collected and reviewed. RESULTS:
      29 cases of DILI were seen by the hepatologist over the 12-month period. Median
      age was 51 (range 18-76) years, 20 (69 percent) were female, and 24 (83 percent)
      were Chinese. TCM were the commonest group of drugs implicated as 15 (52 percent)
      of the patients had presumed DILI from TCM, while four (14 percent) were from
      anti-tuberculosis drugs. 18 (62 percent) presented as hepatitic picture, seven
      (24 percent) as cholestatic, and four (14 percent) as mixed picture. Extrahepatic
      manifestations were seen only in ten percent of patients. Three (ten percent)
      died and one (3 percent) underwent liver transplant for liver failure.
      CONCLUSION: DILI is a common clinical problem with significant mortality. TCM is
      an important cause of DILI in Asia. Further studies on DILI from TCM or other
      complementary medicines are needed.

PMID- 16435053
TI  - Safety among foreign workers and impact on emergency medicine services in
      Singapore.
AB  - INTRODUCTION: This article aims to study work-related injuries through the eyes
      of the foreign workers and correlate the findings with their perception of job
      safety and their level of training received. METHODS: A prospective questionnaire
      based survey was conducted between April and October 2002 in the Emergency
      Department of a secondary level hospital. 285 consecutive foreign workers with
      work-related injuries were enrolled. RESULTS: The majority of the foreign workers
      were of Asian origin, male, and 20-30 years of age. 66 percent had prior working
      experience. 83 percent of those surveyed rated the safety training received as
      "just enough" or better. There was a positive correlation between job skills and
      safety training (rs equals 0.733). 82 percent said that safety equipment were
      available, though only one-half made use of them. 67 percent of the injured
      received some form of first aid at scene, mainly bandaging. 17 percent did not
      receive any first aid because of lack of equipment or first aid training. The two
      most common injuries were wounds to the limbs (33.2 percent) and foreign body
      (FB) entry into the eyes (17.7 percent). Correspondingly, toilet and suture and
      removal of FB in the eye were the two most common procedures done. CONCLUSION: In
      this study, the foreign workers generally felt that the safety and work skills
      training were adequate. However, there are some problems that still need to be
      addressed.

PMID- 16435054
TI  - Detection of F508del mutation in cystic fibrosis transmembrane conductance
      regulator gene mutation among Malays.
AB  - INTRODUCTION: Cystic fibrosis (CF) is one of the common genetic disorders in the
      western world. It has been reported to be very rare in Asian populations.
      According to the Cystic Fibrosis Genetic Analysis Consortium, more than 1,000
      mutations of the CF gene have been identified. The CF gene, named the cystic
      fibrosis transmembrane conductance regulator (CFTR), is located on chromosome 7
      and composed of 27 exons. This study aims to detect possible CFTR gene mutations
      in Malays. METHODS: We analysed 50 blood samples from healthy Malays with no
      symptoms of CF. DNA was extracted from blood using commercially available
      extraction kits (Eppendorf, Germany). Identification of CFTR gene mutation was
      performed using the CF OLA (Oligonucleotide Ligation Assay) kit (Applied
      Biosystems, USA). The PCR-ligation products were electrophoresed on eight percent
      sequagel using an ABI PRISM 377 genetic analyser (Applied Biosystems, USA).
      Electrophoresis data was analysed using the Genotyper software and a report of
      the CF genotype for all loci tested was created using the CF Genotyper Template
      software. Out of 50, one sample (two percent) was detected to have the F508del
      mutation (3bp deletion at exon 10), which is one of the most common CFTR gene
      mutations in Caucasians. RESULTS: The F508del mutation allele was detected in one
      subject. This indicates that she was a CF carrier. CONCLUSION: We report the
      finding of a carrier of the F508del mutation of the CFTR gene in the Malay
      population. Our finding revealed that CF could also affect the Malay population.
      Larger studies are necessary to determine the exact gene frequency of this
      population.

PMID- 16435055
TI  - Characteristics and outcomes of paracetamol poisoning cases at a general hospital
      in Northern Malaysia.
AB  - INTRODUCTION: Paracetamol is available as an over-the-counter medication in many
      countries including Malaysia. This drug has been implicated in many poisoning
      cases admitted to hospitals throughout the country. METHODS: We conducted a three
      year retrospective review of 165 medical records of patients admitted to the
      Penang General Hospital for acute paracetamol poisoning. Cases were identified
      according to the discharge diagnosis documented in their medical records.
      RESULTS: Acute paracetamol poisoning occurred in all major ethnic groups. About
      70 percent of our patients were female. There was minimal involvement of
      children. Admissions were more likely to be due to deliberate ingestions rather
      than accidental poisoning. In most cases, serum concentrations data plotted on
      the Rumack-Matthew nomogram predicted the majority of cases to be unlikely to be
      hepatotoxic, which were consistent with their mild clinical courses. Patients who
      acutely ingested more than 140 mg/kg or predicted to be hepatotoxic, based on
      their serum concentrations, had a significantly longer hospital stay. CONCLUSION:
      Although acute paracetamol poisoning was common, the outcome was generally good.

PMID- 16435056
TI  - Serum soluble transferrin receptor in hypochromic microcytic anaemia.
AB  - INTRODUCTION: The objective of this study was to assess the clinical significance
      of soluble transferrin receptor (sTfR) in hypochromic microcytic anaemia.
      METHODS: Serum sTfR was determined on 91 blood samples with haemoglobin less than
      110 g/L and MCV less than 76 fl or MCH less than 27.0 pg. The samples were
      classified as iron deficiency anaemia (IDA), anaemia of chronic disease (ACD) and
      thalassaemia. ACD was further divided into groups 1 and 2, based on the serum
      ferritin level. RESULTS: The sTfR level in the control was 1.53+/-0.8 mg/L. In
      IDA, the sTfR level was 5.53+/-8.76 mg/L and this was significantly higher
      compared with the control (p-value is less than 0.0001). sTfR levels in ACD
      (3.32+/-3.94 mg/L) and the thalassaemia group(1.64+/-1.02 mg/L) were not
      significantly different from that of the control (p-value is more than 0.05). In
      ACD, the sTfR level in group 1 was significantly higher when compared with the
      control (p-value is less than 0.001) and group 2 (p-value is less than 0.01). A
      significantly higher sTfR/ferritin ratio was observed in IDA (2,368.98+/-7,236.4
      microg/microg) compared to the control (37.6+/-43.7 microg/microg) (p-value is
      less than 0.001). No significant difference was noted between ACD, thalassaemia
      and control (p-value is greater than 0.05). sTfR/ferritin ratio was significantly
      higher in group 1 of ACD when compared with that of control and group 2 (p-value
      is less than 0.001). CONCLUSION: Serum sTfR and sTfR/ferritin ratio are useful
      parameters in hypochromic microcytic anaemia to diagnose iron deficiency
      particularly when associated with chronic inflammation. sTfR can be done
      selectively in ACD patients when ferritin levels are more than 60 microg/L and
      there is a diagnostic dilemma. If sTfR level is raised, a trial of iron therapy
      is suggested for these patients.

PMID- 16435057
TI  - Attitudes towards cancer survivors: a small survey.
AB  - INTRODUCTION: The National Cancer Survivors Day Foundation defines a cancer
      "survivor" as anyone living with a history of cancer--from the moment of
      diagnosis through the remainder of life. Little is known about the size and make
      up of this population or about the medical care experience of and social
      implications for patients who have had a diagnosis of cancer in Singapore. An
      opportunistic survey was undertaken to understand how members of the public
      believe about this population. METHODS: A sample of the general public was
      undertaken during the "CancerVive" event in 2004. Questionnaires regarding
      employment as well as attitudes towards cancer and cancer survivorship were
      distributed. RESULTS: Members of the public held certain misconceptions about
      cancer survivors. They also have certain negative attitudes toward cancer
      survivors. Beliefs and attitudes about cancer are similar for cancer survivors
      and the general public. Although members of the public had positive attitudes
      towards working with cancer survivors, the majority felt that cancer survivors
      should not be given equal opportunities at work, by not employing cancer
      survivors if they were in the position to hire. CONCLUSION: Further research with
      larger and more representative samples needs to be undertaken to extend the
      understanding into cancer survivorship issues.

PMID- 16435058
TI  - Ursodeoxycholic acid therapy for intractable total parenteral nutrition
      associated cholestasis in surgical very low birth weight infants.
AB  - INTRODUCTION: Cholestasis associated with long-term total parenteral nutrition
      (TPN) occurs commonly in very low birth weight (VLBW) infants. Indeed, the
      majority of infants with TPN-associated cholestasis (TPNAC) respond very well to
      TPN withdrawal and full enteral feeding, yet some of them do not respond and have
      the potential for development of intractable cholestasis. It has been
      demonstrated that ursodeoxycholic acid (UDCA) has beneficial effects in treating
      TPNAC in various age groups. Nevertheless, the clinical data of UDCA use in VLBW
      infants, the most vulnerable group, are limited. We report the results of
      administration of UDCA therapy to VLBW infants with intractable TPNAC. METHODS:
      Medical records of VLBW infants who were treated with oral UDCA, at dose of 15-20
      mg/kg/day, for intractable TPNAC were reviewed from 1999-2001. Treatment
      effectiveness was evaluated by monitoring the biochemical hepatic markers,
      including total bilirubin, direct bilirubin, alkaline phosphatase (ALP), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl
      transferase (GGT). RESULTS: A total of 13 infants were identified with the
      diagnosis of intractable TPNAC and they were treated with UDCA therapy. There was
      a significant reduction in serum levels of direct bilirubin, total bilirubin (p
      value equals 0.0001) and AST (p-value equals 0.001). However, the serum levels of
      ALP, ALT and GGT showed a trend of improvement, yet none of them was
      statistically significant. Serum direct bilirubin was noted as the first marker
      to respond to UDCA therapy. It declined steadily during the course of therapy
      except in two intervals at the sixth and twelfth week of therapy that apparently
      associated with severe sepsis. There were no serious side effects noted.
      CONCLUSION: Our series data suggest that UDCA is safe and may be a potential
      treatment for intractable TPNAC if used within two weeks after TPN withdrawal and
      full enteral feeding. Sepsis may alter the effectiveness of UDCA therapy.

PMID- 16435059
TI  - Surgery in patients with advanced liver cirrhosis: a Pandora's box.
AB  - Advanced liver cirrhosis is a relative contraindication for abdominal surgery, as
      such patients are likely to develop postoperative complications and mortalities.
      We describe two patients with liver cirrhosis who developed postoperative
      decompensation and expired after undergoing non-abdominal surgery. We highlight
      that even non-abdominal surgery could incur high mortality in patients with
      Child's class B or C liver cirrhosis. Surgery should be avoided in such patients
      unless it is absolutely necessary. If the procedure is essential and life-saving,
      the patient should be co-managed by a team of surgeon, anaesthesist and
      hepatologist. A full evaluation of the baseline liver status, preoperative
      optimisation, and close postoperative monitoring are required to reduce the risk
      of decompensation and improve survival.

PMID- 16435060
TI  - Exogenously-induced apparent hypermineralocorticoidism associated with ingestion
      of "asam boi".
AB  - A 31-year-old woman presented with a one-week history of headache, generalised
      lethargy, weakness and poor appetite. Clinical examination showed that her blood
      pressure was 200/120 mmHg. On an earlier occasion, her blood pressure was found
      to be normal by a general practitioner whom she last visited three months earlier
      when she had an upper respiratory tract infection. Investigations showed
      hypokalaemia, suppressed serum renin and aldosterone. Further history was taken
      and revealed that she had been craving for guava fruits which she ate with
      flavoured "asam boi" (containing glycyrrhizic acid) at least three spoonfuls
      twice a day for the past six weeks. The hypertension and hypokalaemia resolved
      after two weeks of stopping the "asam boi". Her clinical picture was compatible
      with exogenously-induced hypermineralocortoidism.

PMID- 16435061
TI  - A perplexing case of gastrointestinal haemorrhage.
AB  - Choriocarcinoma is a gestational trophoblastic tumour with a high metastatic
      potential but presentation with gastrointestinal haemorrhage due to jejunal
      mucosal metastasis is very rare. A 25-year-old Nepali woman presented with severe
      anaemia and massive gastrointestinal haemorrhage after normal pregnancy following
      evacuation of a hydatiform mole. During laparotomy, the patient was found to have
      extensive jejunal mucosal metastases.

PMID- 16435062
TI  - Recurrent episodes of arthritis in a hyperthyroid patient.
AB  - Antineutrophil cytoplasmic antibody (ANCA)- associated vasculitis is a
      potentially life-threatening adverse effect of antithyroid medications. We
      present a 22-year-old woman with Graves' disease who developed recurrent episodes
      of arthritis while on treatment with propylthiouracil. A diagnosis of
      propylthiouracil-induced ANCA-associated vasculitis was established only after
      exhaustive rheumatological investigations failed to establish a cause for her
      arthritis. Anti-myeloperoxidase antibody (anti-MPO) titres were grossly elevated
      at 172.7 RU/mL (0-20). Her arthritis resolved promptly following the withdrawal
      of propylthiouracil and the anti-MPO titres declined over 16 months to 66.8
      RU/mL. While she did not develop the life-threatening renal or respiratory tract
      complications, there was a delay in establishing the correct diagnosis with its
      attendant morbidity. This case highlights the need for greater awareness of this
      relatively rare adverse effect of antithyroid medications so as to allow its
      early detection, leading to the prompt cessation of the offending medication.

PMID- 16435063
TI  - Electrocardiographical case. An elderly lady with chest pain. Diagnosis: isolated
      posterior myocardial infarct (MI).
AB  - A 72-year-old woman with diabetes mellitus, hypertension and dyslipidaemia
      presented with severe chest pain of four hours duration. Her electrocardiogram
      (ECG) showed tall R waves in leads V1-2, and ST segment depression in leads V1-
      4, consistent with an isolated posterior myocardial infarction (MI). Emergency
      coronary angiogram showed an occluded left circumflex coronary artery, and
      primary angioplasty and stenting was performed. The ECG criteria for isolated
      posterior MI and pitfalls in using the conventional 12-lead ECG are discussed.

PMID- 16435064
TI  - Early years of radiology in Singapore.

PMID- 16435066
TI  - Does the right leg require extra protection? Five-year review of type 3 open
      fractures of the tibia.

PMID- 16435069
TI  - Levosimendan use reduces matrix metalloproteinase-2 in patients with
      decompensated heart failure.
AB  - BACKGROUND: Extracellular matrix metabolism (ECM) has an important role in left
      ventricular (LV) remodeling in chronic heart failure (CHF). Matrix
      metalloproteinases (MMPs) are involved in the regulation of extracellular matrix
      (ECM) metabolism. We investigated the effect of levosimendan, a novel calcium
      sensitizer, on serum levels of MMP-2. METHODS: Our study population consisted of
      60 consecutive patients with advanced heart failure who were admitted to hospital
      with an acute decompensation of their CHF. Patients were randomized to
      levosimendan (n = 30; 18 men, aged 65 +/- 3 years) or placebo (n = 30; 15 men,
      aged 67 +/- 4 years). Serum MMP-2 levels were assessed before and after treatment
      with levosimendan or placebo, using a commercially available ELISA. RESULTS:
      Serum levels of MMP-2 were reduced from 427 ng/ml 95%CI 372-484 to 371 ng/ml
      95%CI 329-413 in the levosimendan treated group and from 433 ng/ml 95%CI 422-444
      to 425 ng/ml 95%CI 414-436 in the placebo group. Repeated measurements ANOVA
      showed that treatment with levosimendan significantly affected levels of MMP-2 (p
      = 0.019). CONCLUSIONS: The present study showed that levosimendan may
      beneficially affect ECM remodeling in patients with acutely decompensated CHF.
      Whether these effects translate into added clinical benefits, as suggested by an
      improved ejection fraction in the levosimendan group, deserves further
      investigation.

PMID- 16435070
TI  - Enhanced cardioprotection against ischemia-reperfusion injury with combining
      sildenafil with low-dose atorvastatin.
AB  - PURPOSE: Both ATV and SL reduce myocardial infarct size (IS) by enhancing
      expression and activity of NOS isoforms. We investigated whether atorvastatin
      (ATV) and sildenafil (SL) have synergistic effects on myocardial infarct size
      (IS) reduction and enhancing nitric oxide synthase (NOS) expression. METHOD: Rats
      were randomized to nine groups: ATV-1 (1 mg/kg/d); ATV-10 (10 mg/kg/d); SL-0.7
      (0.7 mg/kg); SL-1 (1 mg/kg); ATV-1 + SL-0.7; water alone (controls); 1400W (iNOS
      inhibitor; 1 mg/kg); ATV-10 + 1400W; and ATV-1 + SL-0.7 + 1400W. ATV was
      administered orally for 3 days. SL was administered intraperitoneally 18 h before
      surgery and 1400W intravenously 15 min before surgery. Rats either underwent 30
      min ischemia-4 h reperfusion or the hearts were explanted for immunoblotting and
      enzyme activity tests without being exposed to ischemia. RESULTS: IS (% risk
      area, mean +/- SEM) was smaller in the ATV-10 (13 +/- 1%), SL-1 (11 +/- 2%), SL
      0.7 (18 +/- 2%) and ATV-1 + SL-0.7 (9 +/- 1%) groups as compared with controls
      (34 +/- 3%; P < 0.001), whereas ATV-1 had no effect (29 +/- 2%). ATV-1 + SL-0.7
      (9 +/- 1%) reduced IS more than SL-0.7 alone (p = 0.012). 1400W abrogated the
      protective effect of ATV-10 (35 +/- 3%) and ATV-1 + SL-0.7 (34 +/- 1%). SL-0.7
      and ATV-10 increased phosphorylated endothelial (P-eNOS; 210 +/- 2.5% and 220 +/-
      8%) and inducible (iNOS; 151 +/- 1% and 154 +/- 1%) NOS expression, whereas ATV-1
      did not. These changes were significantly enhanced by ATV-1 + SL-0.7 (P-eNOS, 256
      +/- 2%, iNOS 195 +/- 1%). SL-1 increased P-eNOS (311 +/- 22%) and iNOS (185 +/-
      1%) concentrations. CONCLUSIONS: Combining low-dose ATV with SL augments the IS
      limiting effects through enhanced P-eNOS and iNOS expression.

PMID- 16435071
TI  - Being well-informed about statin is associated with continuous adherence and
      reaching targets.
AB  - BACKGROUND: Statins are life saving drugs in cardiovascular practice. However,
      they still are underprescribed in many situations despite their well-established
      benefits. Adherence may be improved by increased comprehension of the patients.
      METHODS: Patients enrolled into a previous survey were randomized into two groups
      as those, who were informed comprehensively (Group 1) and those not (Group 2).
      202 patients, all of whom were on secondary prevention, were contacted after
      median 15 months of follow up and evaluated whether they continued the statins,
      and reached targets. RESULTS: 102 out of 202 patients were those enrolled into
      Group 1, and 100 of them were those enrolled into Group 2. In Group 1, 62.7% of
      patients were on continuous statin therapy during period between initial and
      secondary contact, whereas, only 46% of patients in Group 2 were on continuous
      statin therapy (p = 0.017). Being well-informed about statin increased the
      likelihood of being on continuous statin therapy after median of 15 months by
      1.977 folds. Concerning targets, 64.7% of those in Group 1 reached the targets,
      whereas, 43% of those in Group 2 reached the targets (p = 0.002). Being well
      informed about statin increased the likelihood of having suggested targets by ATP
      III after median of 15 months by 2.430 folds. CONCLUSION: Providing patients with
      comprehensive knowledge about statins, even in patients, who were already on
      statin therapy, seems not only to improve adherence but also increase the
      percentage of those reaching targets.

PMID- 16435072
TI  - Effect of matrix metalloproteinase inhibition by doxycycline on myocardial
      healing and remodeling after myocardial infarction.
AB  - The aim of conducting this study was to assess the clinical relevance of matrix
      metalloproteinase (MMP) inhibition by doxycycline, an effective MMP inhibitor, in
      a rat model of extensive myocardial infarction (MI) and left ventricular (LV)
      dysfunction. Rats (n = 22) were subjected to extensive anterior MI. Doxycycline
      (25 mg SC, daily) or saline (control) injections were started for nine days
      thereafter. The effect of doxycycline on MMP activity in the infarcted and remote
      myocardium was measured by zymography, in another subgroup (n = 8), nine days
      after MI. Echocardiography and magnetic resonance imaging (MRI) studies were
      performed at one and thirty days after MI to assess LV remodeling and function.
      After 4 weeks, hearts were fixed, and subjected to morphometric and histological
      analysis. Compared with control, doxycycline treatment attenuated MMP-9 and -2
      activity in both infarcted and remote myocardium. Serial echocardiography studies
      showed that doxycycline failed to attenuate scar thinning, LV dilatation and
      dysfunction. MRI study showed that doxycycline impaired LV compensatory
      hypertrophy. Furthermore, compared with control, doxycycline reduced vessel
      density (/mm(2) +/- SEM) in the infarcted myocardium (84 +/- 16 vs. 46 +/-
      9/mm(2), respectively; p < 0.05). Our work suggest that effective MMPs'
      inhibition in the infarcted and remote myocardium by doxycycline does not prevent
      LV remodeling and dysfunction but impairs angiogenesis and compensatory LV
      hypertrophy. Our findings caution against aggressive, non-selective inhibition of
      MMPs in the early healing phase after MI.

PMID- 16435074
TI  - A misquoted mutation in exon16 of the BRCA2 gene.
AB  - A pathogenic mutation in the BRCA2 gene, nt7602del16, has been misquoted as a
      mutation, possibly due to the incorrect inclusion of the last 16 nucleotides of
      exon15 of the BRCA2 gene as part of the intron15-exon16 BRCA2 gene sequence in
      publicly available databases. This was concluded following mutational screening
      by sequencing and enzymatic mapping of the BRCA2 gene exon15-exon16 region in DNA
      from peripheral blood samples from a total of 74 breast cancer and non-breast
      cancer patients as well as healthy individuals and the cell line MCF7. Careful
      interpretation of genetic variants and direct feedback to the corresponding
      sequence databases prevent systemic errors by integrating updated data into
      broadly referenced sources.

PMID- 16435073
TI  - Microarray analysis of promoter methylation in lung cancers.
AB  - Aberrant DNA methylation is an important event in carcinogenesis. Of the various
      regions of a gene that can be methylated in cancers, the promoter is the most
      important for the regulation of gene expression. Here, we describe a microarray
      analysis of DNA methylation in the promoter regions of genes using a newly
      developed promoter-associated methylated DNA amplification DNA chip (PMAD). For
      each sample, methylated Hpa II-resistant DNA fragments and Msp I-cleaved
      (unmethylated+methylated) DNA fragments were amplified and labeled with Cy3 and
      Cy5 respectively, then hybridized to a microarray containing the promoters of 288
      cancer-related genes. Signals from Hpa II-resistant (methylated) DNA (Cy3) were
      normalized to signals from Msp I-cleaved (unmethylated+methylated) DNA fragments
      (Cy5). Normalized signals from lung cancer cell lines were compared to signals
      from normal lung cells. About 10.9% of the cancer-related genes were
      hypermethylated in lung cancer cell lines. Notably, HIC1, IRF7, ASC, RIPK3,
      RASSF1A, FABP3, PRKCDBP, and PAX3 genes were hypermethylated in most lung cancer
      cell lines examined. The expression profiles of these genes correlated to the
      methylation profiles of the genes, indicating that the microarray analysis of DNA
      methylation in the promoter region of the genes is convenient for epigenetic
      study. Further analysis of primary tumors indicated that the frequency of
      hypermethylation was high for ASC (82%) and PAX3 (86%) in all tumor types, and
      high for RIPK3 in small cell carcinoma (57%). This demonstrates that our PMAD
      method is effective at finding epigenetic changes during cancer.

PMID- 16435075
TI  - Patient variables impact lumbar spine dual energy X-ray absorptiometry precision.
AB  - INTRODUCTION: Changes in bone mineral density are used to monitor osteoporosis
      therapy. To determine whether a change in bone mass is clinically significant,
      the precision of bone mineral density measurements must be known. METHODS: We
      therefore measured the impact of vertebral body exclusion on dual energy X-ray
      absorptiometry (DXA) precision. At one university and one Veterans Affairs DXA
      center, three radiology technologists each scanned 30 participants twice, with
      repositioning between scans, to estimate DXA precision. Three International
      Society for Clinical Densitometry-certified physicians reviewed all lumbar spinal
      scans to note the presence of focal structural defects. We calculated precision
      for subsets of vertebrae, and for virtual samples of patients with and without
      physician-identified vertebral focal structural defects. We graphed the
      reciprocal of least significant change versus bone area to determine the
      dependence of precision on interpreted scan area. RESULTS: Within each sample,
      greater interpretable bone area improved precision. The contribution of
      interpreted bone area to precision differed among the samples, ranging from 57 to
      94%. Greater population bone mineral density heterogeneity and presence of focal
      structural defects each decreased precision. CONCLUSION: All bone densitometry
      centers must determine precision using a sample representative of their served
      populations. Failure to do so may lead to incorrect determination of least
      significant change. Population heterogeneity, vertebral body exclusion and
      presence of focal structural defects each decreases precision.

PMID- 16435076
TI  - Changes in the RANK ligand/osteoprotegerin system are correlated to changes in
      bone mineral density in bisphosphonate-treated osteoporotic patients.
AB  - INTRODUCTION: Since the soluble receptor activator of the NF-kappaB ligand
      (sRANKL) as well as the endogenous anti-resorptive cytokine osteoprotegerin (OPG)
      are produced by osteoblasts and given that these cells undergo significant
      changes during antiresorptive treatment, we hypothesized that treatment with
      bisphosphonates (BP) would be accompanied by changes in serum OPG and sRANKL
      levels. METHODS: In a prospective, randomized controlled trial of previously
      untreated postmenopausal women with osteoporosis, oral BP therapy (daily doses of
      either 10 mg alendronate or 5 mg risedronate) in combination with calcium/vitamin
      D was compared to calcium/vitamin D treatment alone (control group). Follow-up at
      2, 6 and 12 months was completed for 56 patients. Standardized spinal X-rays were
      performed at baseline, and DEXA measurements at the femoral neck and trochanter
      were made at baseline and after 1 year. Serum OPG and sRANKL levels were measured
      with a polyclonal antibody-based ELISA system. RESULTS: After 1 year, there was a
      non-significant loss in neck and trochanteric bone mineral density (BMD) in the
      CTR group and a mean increase of 3.3% and 4.6% in the combined BP group (both
      p<0.0001), respectively. Serum levels of C-terminal telopeptides of type I
      collagen (sCTX) and osteocalcin decreased by 12% and 10% at 12 months in the CTR
      group and by 43% and 23% in the combined BP group, respectively (all
      significant). OPG serum levels in the CTR group decreased significantly by 9% at
      2 months (p<0.005) and remained below pre-treatment levels at later time points.
      Both the alendronate- and risedronate-treated patient groups showed unaltered OPG
      levels after 2 months, but they had significantly increased serum levels at 6 and
      12 months. Levels of sRANKL were unchanged throughout the treatment period.
      Univariate regression analysis demonstrated that changes in serum OPG levels
      after 12 months of BP treatment were positively and better correlated to BMD
      changes (trochanter: r=0.59, p<0.0001; neck: r=0.50, p<0.001) than those of sCTX,
      which showed the expected negative correlation to BMD change (trochanter: r=
      0.35, p=0.03; neck: r=-0.23, p=0.16). With multiple regression analyses at 12
      months, R2 values for 1-year changes in trochanteric BMD of 0.33 (OPG alone) and
      0.23 (sCTX alone) were significantly improved to the 0.57 when OPG and sCTX
      changes were combined (p<0.001). Results for the femoral neck were also
      statistically significant R2=0.35, p<0.001). BMD and OPG changes in the CTR group
      were not correlated with each other. CONCLUSIONS: We conclude that with BP
      treatment, changes in serum OPG levels, unlike changes in sCTX levels, are
      positively correlated to changes in BMD response. The BP-related changes in serum
      OPG levels during treatment could result from effects on osteoclastogenesis and
      osteoclast apoptosis as well as from a direct stimulatory effect on osteoblastic
      OPG production. These changes in OPG levels may be used to predict the individual
      response of patients to BP treatment.

PMID- 16435077
TI  - Prevalence and correlates of substance use among young Asian Pacific Islander men
      who have sex with men.
AB  - We examined patterns of substance use among young Asian Pacific Islander (API)
      men who have sex with men (MSM). Participants (N = 496) were recruited from
      sampled venues and were interviewed on substance use, sexual behaviors, and
      attendance at MSM social venues. Substance use prevalence was highest for alcohol
      (94% lifetime, 89% past 6 months), marijuana (61% lifetime, 44% past 6 months),
      and methylenedioxymethamphetamine or ecstasy (58% lifetime, 47% past 6 months).
      During the past 6 months, 24% used an illicit substance weekly or more often, 51%
      used club drugs, and 44% used 3 or more illicit substances. Multivariate models
      identified common and unique correlates of frequent drug use, club drug use, and
      polydrug use. Associations between substance use and sexual risk behaviors also
      emerged. These findings suggest a need to improve substance use and HIV
      prevention intervention efforts for young API MSM.

PMID- 16435079
TI  - Patient and carer perceptions of need and associations with care-giving burden in
      an integrated adult mental health service.
AB  - OBJECTIVE: To identify patients' and carers' perceptions of need in inpatient and
      community settings and investigate the relationship between need and caregiver
      burden. METHOD: The study was conducted across a metropolitan mental health
      service in Sydney, Australia. Patients (n = 407) and carers (n = 50) completed
      the Camberwell Assessment of Need Short Appraisal Schedule. Carers also completed
      a shortened version of the Involvement Evaluation Questionnaire to assess
      caregiver burden. RESULTS: When completing the assessment tools, patients and
      carers in hospital settings were asked to consider the 4 weeks preceding
      hospitalisation; in the community, patients and carers were asked to consider the
      previous 4 weeks. These data show a high percentage of patients in hospital and
      community settings have unmet needs for company, daytime activities and intimate
      relationships. Inpatients had more unmet needs than community based patients.
      Agreement between patients' and carers ratings' of need ranged from 'poor' to
      'moderate'. There was a strong relationship between unmet need and burden from
      the carer's perspective. Patients with and without carers had similar numbers of
      needs. Carers of patients recently admitted to hospital reported a significantly
      higher burden. CONCLUSIONS: Carers of inpatients experienced significantly more
      burden than carers of outpatients. Opportunities to access support, information
      and education should be readily available and not contingent upon demonstrating a
      close familial relationship to the patient. We found that unmet need was
      significantly related to burden, suggesting that meeting patient needs could
      reduce carer burden.

PMID- 16435078
TI  - The "carers' needs assessment for Schizophrenia": an instrument to assess the
      needs of relatives caring for schizophrenia patients.
AB  - OBJECTIVE: For the purpose of service planning, an instrument was developed for
      the systematic assessment of interventions needed by the caregivers of
      schizophrenia patients. METHOD: The development of this instrument was based on
      in-depth interviews and focus groups. It consists of 18 areas describing common
      problems of schizophrenia caregivers. For each of these problem areas several
      possible interventions are offered. Concurrent validity, inter-rater and retest
      reliability were tested among 50 caregivers. RESULTS: The kappa values for the
      inter-rater reliability are predominantly excellent (kappa > 0.75). The values
      for the retest reliability show a wide range between excellent (kappa > 0.75) and
      fair agreement (kappa 0.40-0.60). The significant correlations found between
      summary scores of this new instrument and several sub-scales of the Family
      Problem Questionnaire support the assumption that the concurrent validity is
      satisfactory. CONCLUSION: These results suggest that this instrument is both
      valid and reliable.

PMID- 16435080
TI  - "Pusher syndrome" following cortical lesions that spare the thalamus.
AB  - Stroke patients with "pusher syndrome" show severe misperception of their own
      upright body orientation although visual-vestibular processing is almost intact.
      This dissociation argues for a second graviceptive system in humans for the
      perception of body orientation. Recent studies revealed that the posterior
      thalamus is an important part of this system. The present investigation aimed to
      study the cortical representation of this system beyond the thalamus. We
      evaluated 45 acute patients with and without contraversive pushing following left
      or right-sided cortical lesions sparing the thalamus. In both hemispheres, the
      simple lesion overlap associated with contraversive pushing typically centered on
      the insular cortex and parts of the postcentral gyrus. The comparison between
      pusher patients and controls who were matched with respect to age, lesion size,
      and the frequency of spatial neglect, aphasia and visual field defects revealed
      only very small regions that were specific for the pusher patients with cortical
      damage sparing the thalamus. Obviously, the cortical structures representing our
      control of upright body orientation are in close anatomical proximity to those
      areas that induce aphasia in the left hemisphere and spatial neglect in the right
      hemisphere when lesioned. We conclude that in addition to the subcortical area
      previously identified in the posterior thalamus, parts of the insula and
      postcentral gyrus appear to contribute at cortical level to the processing of the
      afferent signals mediating the graviceptive information about upright body
      orientation.

PMID- 16435081
TI  - Manifestation of multiple sclerosis with paranoid-hallucinatory psychosis.

PMID- 16435082
TI  - Mercury in fish scales as an assessment method for predicting muscle tissue
      mercury concentrations in largemouth bass.
AB  - The relationship between total mercury (Hg) concentration in fish scales and in
      tissues of largemouth bass (Micropterus salmoides) from 20 freshwater sites was
      developed and evaluated to determine whether scale analysis would allow a
      nonlethal and convenient method for predicting Hg concentrations in tissues. The
      relationship between total Hg concentration in untreated scale samples and muscle
      tissue is highly variable. Several different scale treatments were tried in an
      effort to increase the coefficient of determination and thereby enhance the
      effectiveness of this predictive technique. Washing scales with acetone,
      deionized (DI) water, detergent solution, and soap were used in conjunction with
      ultrasonication. The use of a mild soap solution with heating and ultrasonication
      increased the r(2) the most (from 0.69 [untreated scales] to 0.89). However,
      despite treatment, wide predictions of tissue Hg concentration remained. These
      results suggest that application of this technique as an independent method for
      issuance of fish advisories is inappropriate. Nevertheless, our results showed
      that scale analysis has potential for assessing general trends in concentration
      relative to a tissue criterion and for assessing Hg contamination in fish tissue
      as a first-level screen.

PMID- 16435083
TI  - Mycotoxins in poultry feed in Kuwait.
AB  - A survey was conducted at a poultry feed production unit in Kuwait for mycotoxin
      contamination in the samples of yellow maize, soybean meal, wheat bran used as
      raw material and the poultry feed prepared for broiler starter, broiler finisher,
      and layer mash. Individual aflatoxins were determined by high-pressure liquid
      chromatography after immunoaffinity column purification. Repeated analysis
      revealed average aflatoxin concentration in maize at 0.27 ppb (range 0 to 1.69
      ppb), soybean meal at 0.20 ppb (range 0 to 1.27 ppb), wheat bran at 0.15 ppb
      (range 0 to 1.07 ppb), prepared poultry feed for broiler starter at 0.48 ppb
      (range 0 to 3.26 ppb), broiler finisher at 0.39 ppb (range 0 to 1.05 ppb), and
      layer mash at 0.21 ppb (range 0 to 1.30 ppb). Other mycotoxins (ochratoxin,
      fumonisin, deoxynivalenol (DON), and zearalenone), were detected by quantitative
      enzyme-linked immunosorbent assay. The average levels of ochratoxin A ranged from
      4.6 to 9.6 ppb, fumonisin from 1.4 to 3.2 ppm, DON from 0.17 to 0.29 ppm, and
      zearalenone from 46.4 to 67.6 ppb in various commodities and prepared feed
      samples. The study revealed the coexistence of determined mycotoxins, although
      their concentrations in general were found to be lower than the permissible
      levels, wherever defined, for the poultry feed.

PMID- 16435084
TI  - Induction of morphological deformities and moulting alterations in Litopenaeus
      vannamei (Boone) juveniles exposed to the triazole-derivative fungicide tilt.
AB  - A tropical marine bioassay was developed with juveniles of Pacific white shrimp,
      Litopenaeus vannamei, in order to test the acute and sublethal toxicity of Tilt,
      which is the commercial formulation of the fungicide propiconazole. A 10-d acute
      toxicity and a 32-d sublethal test were performed. A median lethal concentration
      (LC50) was determined for different exposure times, resulting in a 24-h LC50 of
      1167 (1101-1386) microg/L (concentration based on active ingredient
      propiconazole), and reaching a threshold LC50 (72-h) at 1043 (1018-1068)
      microg/L. The sublethal exposure test was performed with propiconazole
      concentrations ranging from 367 to 825 microg/L. Animals in most treatments
      showed a significant increase in intermoult duration compared to those in the
      control treatment, although this did not seem to be concentration-dependent.
      However, the shrimps exposed to the sublethal concentrations of this fungicide
      showed morphological deformities, with a significant positive relationship
      between concentration and deformities of the rostrum, paraeopods, and uropods.
      Altogether, the results presented indicate the potential effects of Tilt on
      shrimp, particularly under long-term exposures, although these were found to
      occur at concentrations exceeding those reported in natural environments.

PMID- 16435085
TI  - Physiological responses of hybrid striped bass to aqueous copper in freshwater
      and saltwater.
AB  - Copper (Cu) is an abundant trace metal, and although essential at low levels, it
      is also potentially toxic to aquatic organisms. Mechanisms of toxicity and
      consequences of exposure vary depending on ionoregulatory status (acclimated to
      freshwater or salt water). The goal of this research was to examine the responses
      of hybrid striped bass (Morone chrysops x Morone saxatilis) exposed to Cu in
      freshwater and 15 g/L salt water. In freshwater, a general dose- and time
      dependent pattern of increasing Cu accumulation in gill tissue was evident in
      fish exposed to aqueous Cu (220 and 447 mg/L) for up to 96 hours. The 96-hour
      acute median lethal concentration for freshwater-acclimated hybrid striped bass
      exposed to Cu was 94 mg/L (confidence interval = 62 to 144 mg/L). Plasma
      osmolality and Na(+) concentrations decreased in Cu-exposed fish. Freshwater
      acclimated hybrid striped bass exposed to aqueous Cu (60 mg/L) for 3 weeks
      decreased in mass and accumulated Cu in gill, intestine, and liver. In salt
      water, no mortality occurred, and there were no statistical differences in
      growth, tissue Cu, or plasma ion concentrations in hybrid striped bass exposed to
      Cu compared with control fish. Freshwater-acclimated hybrid striped bass were
      very sensitive to Cu exposure and exhibited responses typical of commonly tested
      teleost fishes; however, the same sensitivity was not observed in salt water
      acclimated fish.

PMID- 16435086
TI  - Occurrence of perfluoroalkyl surfactants in water, fish, and birds from New York
      State.
AB  - Concentrations of perfluorooctanesulfonate (PFOS) and several other
      perfluoroalkyl surfactants (PASs) were determined in nine major water bodies (n =
      51) of New York State (NYS). These PASs were also measured in the livers of two
      species of sport fish (n = 66) from 20 inland lakes in NYS. Finally,
      perfluorinated compounds were measured in the livers of 10 species of waterfowl
      (n = 87) from the Niagara River region in NYS. PFOS, perfluorooctanoic acid
      (PFOA), and perfluorohexanesulfonate (PFHS) were ubiquitous in NYS waters. PFOA
      was typically found at higher concentrations than were PFOS and PFHS. Elevated
      concentrations of PFOS were found in surface waters of Lake Onondaga, and
      elevated concentrations of PFOA were found in the Hudson River. PFOS was the most
      abundant perfluorinated compound in all fish and bird samples. PFOS
      concentrations in the livers of fishes ranged from 9 to 315 ng/g wet weight.
      PFOS, PFOA, and PFOSA (perfluorooctanesulfonamide) concentrations in smallmouth
      and largemouth bass (taken together) caught in remote mountain lakes with no
      known point sources of PAS contamination were 14 to 207, < 1.5 to 6.1, and < 1.5
      to 9.8 ng/g wet weight, respectively. PFOS concentrations in the livers of birds
      ranged from 11 to 882 ng/g wet weight. PFOS concentrations were 2.5-fold greater
      (p = 0.001) in piscivorous birds than in non-piscivorous birds. However, PFOA,
      PFOSA, and PFHS were not found in bird livers. Overall, average concentrations of
      PFOS in fish were 8850-fold greater than those in surface water. An average
      biomagnification factor of 8.9 was estimated for PFOS in common merganser
      relative to that in fish. This study highlights the significance of dietary fish
      in PFOS accumulation in the food chain. Furthermore, our results provide
      information on the distribution of PASs in natural waters, fish, and several bird
      species in NYS.

PMID- 16435087
TI  - Contamination by persistent organic pollutants in dumping sites of Asian
      developing countries: implication of emerging pollution sources.
AB  - In Asian developing countries, large amounts of municipal wastes are dumped daily
      in open dumping sites without proper management. This practice may cause several
      adverse environmental consequences and increased health risk to local
      communities. To elucidate contamination by persistent organic pollutants (POPs)-
      including dichloro-diphenyl-trichloroethane and its metabolites (DDTs),
      hexachlorocyclohexanes (HCHs), chlordanes, hexachlorobenzene (HCB), and
      polychlorinated biphenyls (PCBs)--in such dumping sites, soil samples were
      collected from open dumping sites and respective control sites in Cambodia,
      India, and Vietnam from 1999 through 2001. Our results demonstrated that DDTs,
      PCBs, and HCHs were dominant contaminants in the dumping sites. However, the
      contamination pattern was not consistent, showing higher HCHs in India than in
      Cambodia and Vietnam. Interestingly, in all of the countries, extremely higher
      levels of POPs were observed in the dumping sites compared with those in the
      respective control sites, suggesting significant amplification of POP
      contamination in the dumping sites of Asian developing countries. Mean
      concentrations of DDTs and PCBs were 350 and 140 ng/g dry weight, respectively,
      in the dumping sites of Cambodia and 26 and 210 ng/g, respectively, in India.
      These residue levels were hundreds to thousands times higher than those in
      general soils, implying possible risk to human health of the local communities,
      especially to the rag pickers, including children who work in these sites to
      collect recyclable materials. Composition of DDT compounds suggested their recent
      use in populated areas, which in turn might have caused increased levels of DDTs
      in the open dumping sites. In addition, composition of HCH isomers revealed their
      different use pattern in different countries.

PMID- 16435088
TI  - Alteration of steroid hormone balance in juvenile turbot (Psetta maxima) exposed
      to nonylphenol, bisphenol A, tetrabromodiphenyl ether 47, diallylphthalate, oil,
      and oil spiked with alkylphenols.
AB  - In recent years, concern has been raised about the ability of some classes of
      environmental contaminants to disrupt the endocrine system of both humans and
      wildlife. In this study, juvenile turbots (Psetta maxima) were exposed under
      laboratory conditions to selected waterborne contaminants: oil, oil spiked with
      alkylphenols, bisphenol A, diallylphthalate, tetrabrominated diphenyl ether 47,
      and p-nonylphenol as a positive control for "estrogenic-type" effects. This work
      focused on sex steroids, because these hormones play a key role in the
      reproduction process. Analytical procedures, involving the off-line coupling of
      solid phase extraction and gas chromatography/mass spectrometry, were developed
      for the determination of 12 endogenous sex steroids levels in fish plasma, bile,
      and gonads. Because of the sexual immaturity of the fish used in this study,
      however, only six steroids could be detected in juvenile turbots. Bisphenol A and
      p-nonylphenol exhibited the highest potency towards steroids dynamics, lowering
      the ratio of androgens to estrogens in all three studied matrices. However, these
      two chemicals had different modes of action, because p-nonylphenol induced a
      decrease of androstenedione and 11-ketotestosterone levels, whereas bisphenol A
      exposure led to an elevation of estrone level. Overall, these two chemicals
      seemingly disrupted the activity of some steroidogenesis enzymes, leading to
      serious hormonal imbalance in juvenile turbot.

PMID- 16435090
TI  - NMR assignment of the SRI domain of human Set2/HYPB.

PMID- 16435089
TI  - An evaluation of Australian sediment quality guidelines.
AB  - Interim sediment quality guidelines (ISQGs) adapted recently to Australia from
      North American effects-based guidelines were evaluated with matching chemical and
      toxicological data collected for sediments (n = 103) from Sydney Harbour and
      south coast estuaries of New South Wales. The incidence of toxicity for the test
      battery was low (7%) among samples with all chemical concentrations below ISQG
      Low values, indicating these guidelines are accurate and protective of non-toxic
      conditions. The incidence of toxicity increased greatly (to 73%) when one or more
      ISQG-Low values were exceeded, suggesting that ISQG-Low guidelines are
      appropriate for compliance. Frequent toxic effects (in >75% of samples) were
      associated with chemical concentrations exceeding ISQG-High guidelines. As
      expected, the high guideline values were more predictive of adverse effects than
      the low guidelines. Predictive abilities of ISQGs were not markedly affected by
      normalization of organic compounds to organic carbon or the use of dilute acid
      extractions for metals, suggesting that the guidelines are applicable to a wide
      range of conditions.

PMID- 16435091
TI  - [Diagnostic imaging of splenic disease].
AB  - Primary diseases of the spleen are relatively rare. More frequently, the spleen
      is involved secondarily in hematological, oncological, infectious, immunological,
      vascular, and other systemic diseases. The spleen is the most commonly injured
      organ in blunt abdominal trauma. Anatomical and physiological basics are
      explained, in addition to embryological facts with resulting abnormalities, such
      as accessory and "wandering" spleen, and polysplenia. The most frequent primary
      and secondary diseases of the spleen, including rare diagnoses, are presented and
      illustrated. Hemangioma represents the most common primary benign tumor, and
      lymphoma the most common primary malignant tumor of the spleen. Diagnostic
      imaging does not a allow safe differentiation between Hodgkin's and non-Hodgkin's
      lymphoma. One section deals with the clinical value and diagnostic workup of
      incidentally detected lesions. Simple cysts and calcifications need neither
      clarification nor a follow-up examination. Atypical cysts should be controlled
      within 3-6 months. Additional clarification using CT or MRT should be reserved
      for cases with a strong suspicion of clinically relevant primary or secondary
      splenic disease.

PMID- 16435093
TI  - Determination of trace platinum by supramolecular catalytic kinetic
      spectrofluorimetry of beta-cyclodextrin-platinum-KBrO3-salicylaldehyde
      furfuralhydrazone.
AB  - A supramolecular catalytic kinetic spectrofluorimetric method was developed for
      the determination of platinum(IV) and the possible mechanism of catalytic
      reaction was discussed. The method was based on the fluorescence-enhancing
      reaction of salicylaldehyde furfuralhydrazone (SAFH) with potassium bromate,
      which was catalysed by platinum(IV) in a water-ethanol medium. beta-Cyclodextrin
      (beta-CD) obviously sensitized the determination at pH 5.20 and 25 degrees C.
      Under optimum conditions, the beta-CD-platinum-KBrO3-SAFH supramolecular kinetic
      catalytic reaction system had excitation and emission maxima at 372 and 461 nm,
      respectively. The linear range of this method was 0.60-180 ng ml-1 with a
      relative standard deviation of 1.2%, and the detection limit was 0.18 ng ml-1.
      Investigation of the mechanism and the effects of interferences is presented. The
      proposed method was applied successfully to determine trace platinum(IV) in the
      chemotherapeutic drug cisplatin and serum from patients with satisfactory
      results.

PMID- 16435092
TI  - Liquid chromatography-mass spectrometry (LC-MS): a powerful combination for
      selenium speciation in garlic (Allium sativum).
AB  - Liquid chromatography (LC) hyphenated with both elemental and molecular mass
      spectrometry has been used for Se speciation in Se-enriched garlic. Different
      species were separated by ion-pair liquid chromatography-inductively coupled
      plasma mass spectrometry (LC-ICP-MS) after hot-water extraction. They were
      identified by on-line reversed-phase liquid chromatography-electrospray
      ionization tandem mass spectrometry (RPLC-ESI-MS-MS). Se-methionine and Se
      methylselenocysteine were determined by monitoring their product ions. Another
      compound, gamma-glutamyl-Se-methylselenocysteine, shown to be the most abundant
      form of Se in the garlic, was determined without any additional sample pre
      treatment after extraction and without the need for a synthesized standard.
      Product ions for this dipeptide were detected by LC-ESI-MS-MS for three isotopes
      of Se-78 Se, 80Se: and 82Se. The method was extended to the species extracted
      during in-vitro gastrointestinal digestion. Because both Se-methylselenocysteine
      and gamma-glutamyl-Se-methylselenocysteine have anticarcinogenic properties,
      their extractability and stability during human digestion are very important.
      Garlic was also treated with saliva, to enable detection and analysis of species
      extracted during mastication. Detailed information on the extractability of
      selenium species by both simulated gastric and intestinal fluid are given, and
      variation of the distribution of Se among the different species with time is
      discussed. Although the main species in garlic is the dipeptide gamma-glutamyl-Se
      methylselenocysteine, Se-methylselenocysteine is the main compound present in the
      extracts after treatment with gastrointestinal fluids. Two more, so far unknown
      compounds were observed in the chromatogram. The extracted species and their
      transformations were analysed by combining LC-ICP-MS and LC-ESI-MS-MS. In both
      the simulated gastric and intestinal digests, Se-methionine, Se
      methylselenocysteine, and gamma-glutamyl-Se-methylselenocysteine could be
      determined by LC-ESI-MS-MS by measuring their typical product ions.

PMID- 16435094
TI  - [EGFR-expression in pulmonary neuroendocrine cell hyperplasia].
AB  - 15 cases of pulmonary neuroendocrine cell hyperplasia (carcinoid-tumorlets,
      diffuse idiopathic pulmonary neuroendocrine cell hyperplasia/DIPNECH) and 20
      neuroendocrine pulmonary tumors (10 carcinoid tumors, 5 large cell
      neuroendocrine, and 5 small cell neuroendocrine lung carcinomas) were
      immunohistochemically analyzed for the expression of epidermal growth factor
      receptor (EGFR, = HER-1). All cases of neuroendocrine cell hyperplasia exhibited
      a maximum EGFR expression (score 3 in 100% of cells) showing predominantly
      membranous, partly cytoplasmic staining. 4 ot the 10 carcinoid tumors were
      strongly positive for EGFR, whereas the other 6 were EGFR-negative. A total of
      90% of large cell neuroendocrine and small cell neuroendocrine carcinomas were
      negative for EGFR. Overexpression of EGFR in pulmonary neuroendocrine cell
      hyperplasia might be significant for the pathogenesis of these lesions. As
      DIPNECH is characterized by clinical signs and symptoms including mild cough and
      obstructive functional impairment, a specific antagonistic therapeutic trial
      could aim at blocking EGFR/HER-1 or its subsequent signal transduction pathway.

PMID- 16435095
TI  - [Current morphological diagnosis of malignant lung tumors].
AB  - The histological classification of lung tumors is based upon the 2004 WHO
      classification. Small cell lung cancer (SCLC) is primarily treated by means of
      anti-neoplastic chemotherapy, independently of the tumor stage. In resectable
      stages of non-small cell lung cancer (NSCLC, UICC-stages I and II), complete
      tumor resection is the aim. Therefore, the distinction between SCLC and NSCLC is
      still of particular importance. Currently, great interest is focused on the
      identification of specific therapeutic targets, especially on the inhibition of
      the epidermal growth factor ruptur (EGFR). Today, malignant lung tumors can also
      be classified by means of molecular pathology. Subgroups with different prognoses
      can be identified by gene expression profiling. The expression levels of several
      genes are associated with sensitivity against certain anti-cancer agents.

PMID- 16435096
TI  - [Differential diagnosis of preneoplastic lesions of the pleura and of early
      mesothelioma: immunohistochemical and morphological findings].
AB  - The morphological diagnosis of small mesothelial lesions in pleural biopsies is
      gaining importance in view of more aggressive, multimodal therapeutic options and
      of medicolegal aspects if a malignant mesothelioma is diagnosed. We present a
      light microscopically and immunohistochemically based morphological
      classification for the planning of further clinical follow-up procedures. A
      reactive mesothelial hyperplasia heals without scars. Mesothelial inclusions in
      pleuritic scars are common in recurrent pleuritis and must not be confused with
      an epithelioid component of a desmoplastic mesothelioma. In case of atypical
      mesothelial proliferations, further diagnostic procedures have to be performed to
      obtain a clear diagnosis of malignancy. Mesothelioma in situ is the first
      morphological step in neoplastic mesothelial changes, also with regard to
      medicolegal aspects for the unambiguous diagnosis of a mesothelioma. Early
      infiltrative growth is characteristic of so called early mesothelioma. A useful
      immunohistochemical panel for the differential diagnosis consists of anti
      cytokeratin, Ck 5/6, calretinin, EMA and MiB-1, whereas the immunohistochemical
      detection of telomerase is not helpful.

PMID- 16435098
TI  - Polymerase chain reaction screening for fungemia and/or invasive fungal
      infections in patients with hematologic malignancies.
AB  - INTRODUCTION: Invasive fungal infections (IFIs) are a life-threatening
      complication in patients with hematologic malignancies, mainly in acute leukemia
      patients, following chemotherapy. IFI incidence is increasing, and associated
      mortality remains high due to unreliable diagnosis. Antifungal drugs are often
      limited by inadequate antimicrobial spectrum and side effects. Thus, the
      detection of circulating fungal DNA has been advocated as a rapid, more sensitive
      diagnostic tool. PATIENTS AND METHODS: Between June 01 and January 03, weekly
      blood samples (1,311) were screened from 193 patients undergoing intensive
      myelosuppressive or immunosuppressive therapy. IFI cases were classified
      according to European Organization for Research and Treatment of Cancer/Mycoses
      Study Group criteria. Fungal DNA was extracted from whole blood and amplified
      using polymerase chain reaction (PCR) published primers that bind to the
      conserved regions of the fungal 18S rRNA gene sequence. In our study, two or more
      consecutive positive samples were always associated with fungal disease. RESULTS:
      PCR screening predicted the development of IFI to be 17 days (median). This test
      had a specificity of 91.1% and a sensitivity of 75%. IFI incidence was 7.8%.
      DISCUSSION: Therefore, our results confirm the potential usefulness of PCR serial
      screening and the clinical applicability in everyday routine. PCR screening
      offers a noninvasive repeatable aid to the diagnosis of IFI.

PMID- 16435099
TI  - Atypical pulmonary embolism of port catheter fragments in oncology patients.
AB  - GOALS OF WORK: Embolization of venous catheter fragments to the pulmonary
      vasculature is a very rare form of pulmonary embolism which is only sporadically
      reported in the literature. The incidence and clinical picture of this
      complication are unknown. PATIENT AND METHODS: In this retrospective analysis
      between 1999 and 2004, in our clinic, 1,014 port catheters were implanted. In
      this 5-year period, the patients' files were screened for the incidence of
      pulmonary embolism of catheter fragments and the accompanying complication rate.
      MAIN RESULTS: In 11 patients, port catheter dislodgment and embolism into the
      pulmonary artery occurred. In all the patients' port examination by fluoroscopy,
      catheter dislocation and embolization were shown. In these 11 patients, no
      obvious clinical signs indicating dislocation of catheter fragments into the
      pulmonary circulation were found. None of these patients demonstrated respiratory
      symptoms. Heart rate, blood pressure, respiration frequency, and even oxygen
      saturation were normal. In 7 of the 11 patients, malfunction of port catheter was
      the first indicator of catheter dislocation. In four patients, embolized catheter
      fragments were an incidental finding. The main cause of catheter embolization was
      the pinch off syndrome. All embolized catheter fragments were retrieved by a
      'goose-neck' snare without complication. CONCLUSION: These results suggest that
      the migration of fractured catheter into the pulmonary artery occurs in 1% of the
      central port catheter implantation. It is often asymptomatic, and malfunction of
      the catheter may be the first sign of this complication. The pinch off syndrome
      might be prevented by using the internal jugular vein or by implantation of the
      port catheter more laterally in the subclavian vein.

PMID- 16435097
TI  - Peripartum urinary incontinence in a racially diverse obstetrical population.
AB  - To determine the rates of urinary incontinence in a racially diverse, tertiary
      care obstetrical population during the third trimester and postpartum using a
      validated symptom-screening questionnaire. Third trimester prenatal patients
      receiving obstetric care at Loyola University Medical Center between March and
      November 2003 participated in this prospective study approved by the
      Institutional Review Board. Third-trimester participants completed the 15-item,
      validated Medical, Epidemiological, and Social Aspects of Aging (MESA)
      questionnaire and the Hunskaar Severity Index. The MESA was readministered to
      participants during a 6- to 8-week postpartum visit. One hundred and thirteen
      women completed antenatal and postpartum MESAs. Seventy-four percent (83 of 113)
      of the patients in the third trimester were categorized as incontinent. The
      postpartum incontinence rates decreased to 44% (50 of 113). Twenty-one percent
      (24 of 113) of the participants after delivery reported pure stress incontinence,
      3% (3 of 113) urge incontinence, and 20% (23 of 113) mixed incontinence. Only 4%
      (5 of 113) of the women developed de novo incontinence postpartum: three reported
      symptoms of pure stress incontinence and two reported symptoms consistent with
      urge incontinence. The MESA questionnaire identifies more women with antenatal
      and postpartum urinary incontinence than currently described in the literature.

PMID- 16435100
TI  - [Minimally invasive treatment of monocondylar tibial plateau fractures.
      Percutaneous reduction and small fragment osteosynthesis].
AB  - BACKGROUND: Treatment of displaced tibial plateau fractures is often complicated
      by high-energy trauma and soft tissue damage. Therefore, numerous techniques such
      as indirect or arthroscopically controlled reduction and percutaneous
      osteosynthesis have been described to reduce the additional surgical trauma.
      MATERIAL AND METHODS: Twenty-three fractures (AO type 41-B2/3, Schatzker type II
      IV) were treated with percutaneous, fluoroscopically guided reduction combined
      with small fragment osteosynthesis using a radius T-plate. In none of the patient
      was cancellous bone graft performed. Only in one case was arthrotomy necessary
      because of uncertain image intensification findings in an obese patient. One
      revision was done for a 4-mm step caused by an over reduced rim fragment.
      Fracture healing and full weight bearing were achieved after 8-12 weeks. Neither
      secondary displacement nor implant loosening was seen under primary functional
      treatment without immobilization. RESULTS: Functional recovery showed a mean ROM
      of 114 degrees after 6 weeks and 121 degrees after 3 months. The radius T-plate
      offers enough stability to allow primary functional treatment due to early
      recovery of joint motion. Percutaneous reduction and small fragment
      osteosynthesis is a less invasive approach in the treatment of displaced
      monocondylar tibial plateau fractures.

PMID- 16435101
TI  - [Health services research in psychosocial medicine].
AB  - The following article presents aspects of the field of psychosocial medicine in
      Germany from the perspective of health services research. First, the tasks and
      topics of health services research are listed. The identification and appropriate
      treatment of people with mental disorders is one of the core themes of
      psychosocial health care; therefore, a brief overview of research results on the
      epidemiology of mental disorders is first presented. The primary focus of this
      article is then to provide a description and analysis of the structures of
      psychosocial care in inpatient and outpatient settings. Research findings
      concerning treatment processes and the result of these processes are additionally
      presented. The findings show that there is still a considerable lack of research
      results regarding the treatment of patients with mental disorders, as is also the
      case in other health care areas. An important empirical basis for rationally
      founded treatment planning in this area is thus lacking.

PMID- 16435102
TI  - [Patient safety in hospitals--a health services research issue].
AB  - Health services research as a multidisciplinary approach to transfer scientific
      results and clinical experience to health care includes quality research as one
      of its main topics. Quality research describes the total of conditions, which
      hinder or promote quality of care as one important output factor of health care.
      At present, patient safety research is one of the central issues of quality
      research, as preventable adverse events represent the most substantial
      consequences of problems in quality. Research issues start with epidemiological
      data, which are lacking in Germany, and the transfer of international data to the
      German health care system. Reporting instruments including critical incident
      reporting systems have to be validated, patient safety indicators should be
      developed, under consideration of the use of administrative data. Patient safety
      research addresses the effect of public disclosure of adverse events, errors and
      injury in respect to improvement of care and should analyse as well as elaborate
      prevention strategies for the most important adverse events and errors. Team
      factors such as communication and supervision and determinants of safety culture
      are issues, which illustrate the significant role of management theory and
      organisational research.

PMID- 16435103
TI  - Interleukin-10-1082 promoter polymorphism in association with cytokine production
      and sepsis susceptibility.
AB  - OBJECTIVE: To investigate the -1082 (A/G) polymorphism in the promoter of the IL
      10 gene in terms of IL-10 production from stimulated peripheral blood mononuclear
      cells (PBMC) and to evaluate the relationship of this polymorphism with
      susceptibility to severe sepsis and the outcome of the disease. DESIGN: Case
      control study. SETTING: Research laboratory of Molecular Biology and Immunology
      and University Hospital ICU, Faculty of Medicine, Trakia University. PATIENTS: A
      total of 53 healthy volunteers and 33 patients in ICU meeting the criteria for
      severe sepsis were included. MEASUREMENTS AND RESULTS: The amplification
      refractory mutation system PCR was used for IL-10-1082 polymorphism detection.
      Isolated PBMC were stimulated with either C3-binding glycoprotein (C3bgp),
      lipopolysaccharide (LPS), phytohemagglutinin (PHA),or pokeweed mitogen (PWM). IL
      10 production was measured in culture supernatants. The AA genotype was
      associated with lower IL-10 production in LPS-, PHA- or PWM-stimulated healthy
      PBMC. Patients with severe sepsis had significant elevation of A allele, compared
      with healthy controls (74.2% vs 52.8%; p=0.0062). Carriage of at least one copy
      of IL-10-1082 G allele in sepsis patients and in healthy controls resulted in a
      statistically significant increase in IL-10 production from stimulated PBMC.
      Surviving sepsis patients had a significant decrease of IL-10-1082 allele G
      frequency, compared with controls (17% vs 47.2%; p=0.012). An association between
      increased IL-10 production and poor outcome from sepsis was observed. CONCLUSION:
      The A allele of the -1082 polymorphism in the interleukin-10 gene promoter is
      associated with sepsis susceptibility, whereas G allele is associated with higher
      stimulated interleukin-10 production and increased mortality in severe sepsis.

PMID- 16435104
TI  - Oral care reduces incidence of ventilator-associated pneumonia in ICU
      populations.
AB  - OBJECTIVE: To examine whether oral care contributes to preventing ventilator
      associated pneumonia (VAP) in ICU patients. DESIGN: Nonrandomized trial with
      historical controls. SETTING: A medical-surgical ICU in a university hospital.
      PATIENTS: 1,666 mechanically ventilated patients admitted to the ICU.
      INTERVENTION: Oral care was provided to 1,252 patients who were admitted to the
      ICU during period between January 1997 and December 2002 (oral care group), while
      414 patients who were admitted to the ICU during period between January 1995 and
      December 1996 and who did not receive oral care served as historical controls
      (non-oral care group). MEASUREMENTS AND RESULTS: Incidence of VAP(episodes of
      pneumonia per 1000 ventilator days) in the oral care group was significantly
      lower than that in the non-oral care group (3.9 vs 10.4). The relative risk of
      VAP in the oral care group compared to that in the non-oral care group was 0.37,
      with an attributable risk of -3.96%. Furthermore, length of stay in ICU before
      onset of VAP was greater in the oral care than in the non-oral care group (8.5+/
      4.6 vs 6.3+/-7.5 days). However, no significant difference was observed in either
      duration of mechanical ventilation or length of stay between the groups (5.9+/
      10.8 vs 6.0+/-8.8 days and 7.5+/-11.5 vs 7.2+/-9.5 days, respectively).
      Pseudomonoas aeruginosa was the most frequently detected bacteria in both groups.
      Number of potentially pathogenic bacteria in oral cavity was significantly
      reduced by single oral care procedure. CONCLUSION: Oral care decreased the
      incidence of VAP in ICU patients. DESCRIPTOR: Pulmonary nosocomial infection.

PMID- 16435105
TI  - Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related
      phenotypes.
AB  - AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor-gamma co-activator
      1alpha (PPARGC1A) is a transcriptional co-activator with a central role in energy
      expenditure and glucose metabolism. Several studies have suggested that the
      common PPARGC1A polymorphism Gly482Ser may be associated with risk of type 2
      diabetes, with conflicting results. To clarify the role of Gly482Ser in type 2
      diabetes and related human metabolic phenotypes we genotyped this polymorphism in
      a case-control study and performed a meta-analysis of relevant published data.
      MATERIALS AND METHODS: Gly482Ser was genotyped in a type 2 diabetes case-control
      study (N=1,096) using MassArray technology. A literature search revealed
      publications that examined Gly482Ser for association with type 2 diabetes and
      related metabolic phenotypes. Meta-analysis of the current study and relevant
      published data was undertaken. RESULTS: In the pooled meta-analysis, including
      data from this study and seven published reports (3,718 cases, 4,818 controls),
      there was evidence of between-study heterogeneity (p<0.1). In the fixed-effects
      meta-analysis, the pooled odds ratio for risk of type 2 diabetes per Ser482
      allele was 1.07 (95% CI 1.00-1.15, p=0.044). Elimination of one of the studies
      from the meta-analysis gave a summary odds ratio of 1.11 (95% CI 1.04-1.20,
      p=0.004), with no between-study heterogeneity (p=0.475). For quantitative
      metabolic traits in normoglycaemic subjects, we also found significant between
      study heterogeneity. However, no significant association was observed between
      Gly482Ser and BMI, fasting glucose or fasting insulin.
      CONCLUSIONS/INTERPRETATION: This meta-analysis of data from the current and
      published studies supports a modest role for the Gly482Ser PPARGC1A variant in
      type 2 diabetes risk.

PMID- 16435107
TI  - The influence of climate variability on numbers of three waterbird species in
      Western Port, Victoria, 1973-2002.
AB  - Seasonal and annual movements of Australian waterbirds are generally more complex
      than those of their Northern Hemisphere counterparts, and long-term data are
      needed to understand their relationships with climatic variables. This paper
      explores a long-term (1973-2002) set of waterbird counts from coastal Victoria
      and relates them to climatic data at local and continental scales. Three species
      (Black Swan Cygnus atratus, White-faced Heron Egretta novaehollandiae and Grey
      Teal Anas gracilis) were chosen for this analysis. Black Swans have large local
      breeding populations near the study region; White-faced Herons have smaller local
      breeding populations and Grey Teal breed extensively in ephemeral inland
      floodplains, such as those in the Murray-Darling Basin. All showed significant
      relationships with streamflow, regional rainfall and the Southern Oscillation
      Index (SOI) at appropriate scales and time-lags, with streamflow explaining the
      most variance. Black Swans showed a strong seasonal cycle in abundance and local
      climate variables had the greatest influence on the counts. Numbers were
      positively correlated with streamflow in southern Victoria three to six seasons
      before each count. Broader-scale climatic patterns were more important for the
      other two species. Numbers of White-faced Herons were positively correlated with
      streamflow or rainfall over various parts of Australia seven to nine seasons
      before each count. Numbers of Grey Teal showed weak seasonal cycles, and were
      negatively correlated with rainfall in Victoria or the Murray-Darling Basin in
      the seasons before or during each count, and positively with streamflow in the
      Murray-Darling Basin 15-18 months before each count.

PMID- 16435108
TI  - Specificity controls for immunocytochemistry.
AB  - Antibodies have been in widespread use for more than three decades as invaluable
      tools for the specific detection of proteins or other molecules in biological
      samples. In spite of such a long experience, the field of immunocytochemistry is
      still troubled by spurious results due to insufficient specificity of antibodies
      or procedures used. The importance of keeping a high standard is increasing
      because massive sequencing of entire genomes leads to the identification of
      numerous new proteins. All the identified proteins and their variants will have
      to be localized precisely and quantitatively at high resolution throughout the
      development of all species. Consequently, antibody generation and
      immunocytochemical investigations will be done on a large scale. It will be
      economically important to secure an optimal balance between the risk of
      publishing erroneous data (which are expensive to correct) and the costs of
      specificity testing. Because proofs of specificity are never absolute, but rather
      represent failures to detect crossreactivity, there is no limit to the number of
      control experiments that can be performed. The aims of the present paper are to
      increase the awareness of the difficulties in proving the specificity of
      immunocytochemical labeling and to initiate a discussion on optimized standards.
      The main points are: (1) antibodies should be described properly, (2) the
      labeling obtained with an antibody to a single epitope needs additional
      verification and (3) the investigators should be required to outline in detail
      how they arrive at the conclusion that the immunocytochemical labeling is
      specific.

PMID- 16435109
TI  - Unilateral occipital hyperhidrosis following Chiari I decompression: case report
      and a review of the literature.
AB  - INTRODUCTION: Paroxysmal unilateral cephalic hyperhidrosis is a rare disorder of
      the autonomic nervous system. CASE REPORT: We report an adult male who developed
      this disorder almost 20 years after posterior fossa decompression for Chiari I
      malformation with syringomyelia as a child. Further, the patient presented with
      spastic diplegia. To date, this patient has refused further operative
      intervention. The medical literature is reviewed regarding this unusual
      phenomenon. CONCLUSION: To our knowledge, hyperhidrosis of the occiput has not
      been previously reported in a patient with Chiari I malformation with an
      associated syringomyelia.

PMID- 16435110
TI  - Inter-examiner reliability in the assessment of low back pain (LBP) using the
      Kirkaldy-Willis classification (KWC).
AB  - Reliable classification systems and clinical tests are sought for the care of
      patients with low back pain (LBP). The objectives of this clinical study were to
      evaluate inter-examiner reliability in the classification of patients with LBP,
      the influence of radiological findings on the classification and the reliability
      of some clinical tests. Two examiners independently assessed 50 outpatients with
      LBP. Inter-examiner reliability in classification of patients with LBP using
      Kirkkaldy-Willis classification (KWC) system and in 30 clinical tests was
      calculated as percentage agreement and kappa coefficients (kappa). Inter-examiner
      reliability was excellent (kappa>0.8) for classification according to KWC.
      Radiological findings did not influence the reliability. Age of the patient,
      movement range, and pain and neurological signs seemed to guide the decision on
      classification. The reliability of clinical tests was good (kappa>0.6) in 6 tests
      and moderate (kappa>0.4) in 12 tests. Good inter-examiner reliability was found
      for the SLR test, movement range and sensibility testing with spurs in dermatome
      areas. We conclude that the KWC for classifying patients with LBP seems to be a
      reliable classification system depending on a few key observations and that
      moderate and good inter-examiner reliability can be achieved in several clinical
      tests in the assessment of LBP.

PMID- 16435112
TI  - [Post-operative pain management in orthopaedic surgery and traumatology].
AB  - Provision of sufficient post-operative pain therapy is an obligation in the
      clinical management of patients. A wide range of medical, technical and
      organizational options is used to improve post-operative pain management in
      orthopaedic surgery. Measurement of pain is as important as the correct use of
      analgesics and application techniques. Standardized pain therapy algorithms
      should facilitate autonomous treatment of patients. Additional procedures like
      patient-controlled analgesia or local catheter for pain are necessary for
      individualized or operation-specific pain therapy. The balanced combination in
      postoperative pain therapy could reduce side effects and complication rates,
      increase mobility and enhance patient satisfaction.

PMID- 16435113
TI  - MDCT is better than stress perfusion imaging for detecting CAD--Against.

PMID- 16435114
TI  - MSCT is better than stress perfusion imaging for detecting CAD--For.

PMID- 16435115
TI  - 11C-methionine PET/CT in 99mTc-sestamibi-negative hyperparathyroidism in patients
      with renal failure on chronic haemodialysis.
AB  - PURPOSE: Scintigraphic localisation of parathyroid glands is often unsuccessful
      in patients with renal failure on chronic haemodialysis who have secondary
      hyperparathyroidism (HPT). The purpose of this study was to investigate the use
      of (11)C-methionine PET/CT to detect hyperfunctioning parathyroid glands in
      patients with renal failure on chronic haemodialysis who had (99m)Tc-sestamibi
      negative HPT. METHODS: (11)C-methionine PET/CT was performed in 18 patients (11
      women and 7 men, aged 42-79 years; mean age 57.8 years) on haemodialysis for
      renal failure (2-14 years' duration), with normo-, hypo- or hypercalcaemia and
      HPT not localised by either dual-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi
      subtraction scans or dual-phase (99m)Tc-sestamibi scans. RESULTS: In three of ten
      patients with normo- or hypocalcaemic HPT there was increased (11)C-methionine
      accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed
      increased uptake: in five of these patients increased (11)C-methionine
      accumulation was present in one gland, while in two it was demonstrated in two
      glands. All patients also had high-resolution ultrasound of the neck and were
      treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the
      four glands. Regardless of their size, all glands with abnormal (11)C-methionine
      parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia.
      All patients developed post-parathyroidectomy hypoparathyroidism and one patient
      with normocalcaemic HPT relapsed 8 months after surgery. CONCLUSION: These data
      suggest that (11)C-methionine PET/CT may be used to identify hyperfunctioning
      parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when
      conventional (99m)Tc-sestamibi imaging is non-localising.

PMID- 16435116
TI  - Cross-camera comparison of SPECT measurements of a 3-D anthropomorphic basal
      ganglia phantom.
AB  - PURPOSE: SPECT examinations of neurotransmitter systems in the brain have to be
      comparable between centres to generate a comprehensive data pool, e.g. for
      multicentre studies. Equipment-specific effects on quantitative evaluations and
      corresponding methods for compensation, however, have been insufficiently
      examined. Previous studies have shown that quantitative results may vary
      significantly according to the imaging equipment used, thereby affecting clinical
      interpretation of the data. The aim of this study was to determine correction
      factors for common camera/collimator combinations based on standardised
      measurements of an anthropomorphic 3D basal ganglia phantom to compensate for the
      effects of different SPECT camera/collimator equipment. The latter may serve as a
      model for human studies of the dopaminergic system. METHODS: The striatum and
      background chambers of a commercially available phantom (RSD Alderson) were
      filled with various( 123)I concentrations encompassing specific
      striatum/background ratios from 0.6 to 16.1. This setup was imaged with the
      following four camera/collimator combinations: Siemens Multispect 3 fitted with
      LEHR and( 123)I parallel-hole collimators, Siemens ECAM with LEHR parallel-hole
      collimators and Philips Prism 3,000 fitted with LEHR fanbeam collimators, using
      standardised protocols for acquisition and reconstruction. All scans were
      automatically co-registered to a SPECT template of the phantom and quantified
      using a 3D volume of interest (VOI) map based on a CT scan of the phantom. All
      striatal/background ratios calculated by SPECT were compared with the true ratios
      calculated from the measurements in a well counter. Regression analyses were
      performed and recovery correction factors between measured and true ratios
      determined. RESULTS: The relation between true and measured ratios could be
      sufficiently described by a linear regression for each camera/collimator
      combination without relevant improvement when using second-order polynomial
      regression models. The recovery correction factors and standard errors were
      2.04+/-0.04 for the Philips Prism 3,000, 2.67+/-0.03 for the Siemens Multispect
      3/LEHR parallel-hole collimators, 2.15+/-0.03 for the Siemens Multispect 3/(123)I
      collimators and 2.81+/-0.03 for the Siemens ECAM. Percentage recovery ranged from
      36% to 49%. CONCLUSION: Measurements of a 3D basal ganglia phantom with various
      imaging devices revealed linear correlations between measured and true
      striatal/background ratios. Based on these findings, adjustment of quantitative
      results between different equipment seems possible, provided that acquisition,
      reconstruction and evaluation are adequately standardised. The use of identical
      evaluation methods in phantom and patient studies (comparable shape, size and
      location of the VOIs) might allow transfer of the calculated correction factors
      from phantom to studies of the dopaminergic system in patients.

PMID- 16435117
TI  - Fixed budgets as a cost containment measure for pharmaceuticals.
AB  - In Vasterbotten County, Sweden, there are two health centers which (in contrast
      to all other health centers in the region) bear strict responsibility over their
      pharmaceutical budget. This study examined whether the prices and quantities of
      pharmaceuticals prescribed by physicians working at these health centers differ
      significantly from those prescribed by physicians at health centers with open
      ended budgets. Estimation results using matching methods, which allows us to
      compare similar patients at the different health centers, show that the
      introduction of fixed pharmaceutical budgets did not affect physicians'
      prescription behavior, indicating that fixed budgets may not be an efficient
      measure to reduce costs. Another explanation is that the health centers under
      study already had taken measures to contain costs, making it hard to further
      reduce costs.

PMID- 16435118
TI  - Genome-wide analysis of cyclin family in rice (Oryza Sativa L.).
AB  - The cyclins together with highly conserved cyclin-dependent kinases regulate cell
      cycle progression in plants. Although extensive and systematic study on cell
      cycle mechanisms and cyclin functions in yeasts and animals has been carried out,
      only a small number of plant cyclins have been characterized and classified
      functionally and phylogenetically. We identified several types of cyclin genes in
      the rice genome and characterized them by phylogenetic, tandem and segmental
      duplications analyses. Our results indicated that there were at least 49
      predicted rice cyclin genes in the rice genome, and they were distributed on 12
      chromosomes. Of these cyclins, one possessed only cyclin_C domain and no cyclin_N
      domain, and the remaining 48 cyclins with cyclin_N domains were classified as
      nine types based on evolutionary relationships. Eight of these nine types were
      common between rice and Arabidopsis, whereas only one, known as F-type cyclins,
      was unique to rice. No homologues of the F-type cyclins in plants could be
      retrieved from the public databases, and reverse transcription-PCR analysis
      supported an existence of the F-type cyclin genes. Sequence alignment suggested
      that the cyclin genes in the rice genome experienced a mass of gene tandem and
      segmental duplications occurred on seven chromosomes related to the origins of
      new cyclin genes. Our study provided an opportunity to facilitate assessment and
      classification of new members, serving as a guide for further functional
      elucidation of rice cyclins.

PMID- 16435119
TI  - The chloroplast genome of Nicotiana sylvestris and Nicotiana tomentosiformis:
      complete sequencing confirms that the Nicotiana sylvestris progenitor is the
      maternal genome donor of Nicotiana tabacum.
AB  - The tobacco cultivar Nicotiana tabacum is a natural amphidiploid that is thought
      to be derived from ancestors of Nicotiana sylvestris and Nicotiana
      tomentosiformis. To compare these chloroplast genomes, DNA was prepared from
      isolated chloroplasts from green leaves of N. sylvestris and N. tomentosiformis,
      and subjected to whole-genome shotgun sequencing. The N. sylvestris chloroplast
      genome comprises of 155,941 bp and shows identical gene organization with that of
      N. tabacum, except one ORF. Detailed comparison revealed only seven different
      sites between N. tabacum and N. sylvestris; three in introns, two in spacer
      regions and two in coding regions. The chloroplast DNA of N. tomentosiformis is
      155,745 bp long and possesses also identical gene organization with that of N.
      tabacum, except four ORFs and one pseudogene. However, 1,194 sites differ between
      these two species. Compared with N. tabacum, the nucleotide substitution in the
      inverted repeat was much lower than that in the single-copy region. The present
      work confirms that the chloroplast genome from N. tabacum was derived from an
      ancestor of N. sylvestris, and suggests that the rate of nucleotide substitution
      of the chloroplast genomes from N. tabacum and N. sylvestris is very low.

PMID- 16435120
TI  - Rapid improvement of distal vasculitis in PAN related to hepatitis B with
      alprostadil infusion: a case report.
AB  - Polyarteritis nodosa (PAN) related to hepatitis B is an uncommon vasculitis that
      is sometimes associated with the rapid progression of distal ischemia. A few
      recent reports have proposed the use of antiviral therapy. However, there is not
      yet a consensus for the standard treatment of this disease entity and none of
      these treatments have been focused on fast symptomatic improvement. We describe
      here a 39-year-old female patient with PAN related to hepatitis B infection who
      completely recovered from the acutely progressing ischemic manifestations of her
      distal extremities with the use of alprostadil infusion (prostaglandin E1). The
      reactivation of her hepatitis B infection after glucocorticoid and
      cyclophosphamide therapy was successfully managed by the antiviral lamuvudine
      therapy. Most importantly, the vasodilator together with the conventional therapy
      may be desirable in the early stages of the disease before irreversible ischemic
      tissue damage can occur.

PMID- 16435121
TI  - Ochronotic arthropathy, an approach to osteoarthritis bone remodelling.
AB  - The objective is to use hip ochronotic arthropathy for an indirect approach to
      osteoarthritis bone remodelling in a human joint via an identified causal
      chondropathy. The method is via radiology connecting pathology and nosology,
      based on the study of seven ochronotic femur heads excised in alcaptonuric
      patients. Due to the brittleness of ochronotic cartilage, bone remodelling
      similar to that of hip osteoarthritis exists with diffuse narrowing of the
      interarticular space and (except in one case modified by intermediary surgery)
      poorly developed osteophytes. Ochronotic arthropathy is only a privileged model
      of osteoarthritis bone remodelling, the pathology of which might well evidence
      the stages of the process, with marking by pigmented cartilage remnants Thus it
      may lead to various reflections in rheumatology, among others concerning the
      respective radiological hip images of osteoarthritis and rheumatoid arthritis.
      The use of the pathology-radiology files provided by hip surgery of ochronotic
      arthropathy might offer a useful reference model for investigating various
      aspects of osteoarthritis.

PMID- 16435122
TI  - DNA methylation pattern in pig in vivo produced embryos.
AB  - DNA methylation/demethylation pattern, determined by 5-methylcytosine (5-MeC)
      immunostaining, was evaluated in porcine "in vivo" produced embryos from zygote
      up to the blastocyst stage. In one-cell stage embryos, only the maternal
      pronucleus showed a positive labeling whilst the paternal pronucleus showed
      almost no labeling. The intensity of labeling is high until the late morula
      stage. Blastocysts containing less than 100 cells showed the same intensity of
      labeling in both the inner cell mass (ICM) nuclei and the trophectodermal (TE)
      cell nuclei. Interestingly, with further cell multiplication, cells of the ICM
      became more intensively labeled when compared to TE cells. This distinct
      methylation pattern is even more profound in blastocysts containing about 200-300
      cells and is not caused by the difference in the cell volume of ICM and TE cells.

PMID- 16435123
TI  - Towards functional glycomics by localization of binding sites for tissue lectins:
      lectin histochemical reactivity for galectins during diethylstilbestrol-induced
      kidney tumorigenesis in male Syrian hamster.
AB  - Endogenous lectins act as effectors of cellular activities such as growth
      regulation, migration, and adhesion. Following their immunohistochemical
      localization in our previous study (Saussez et al. in Histochem Cell Biol 123:29
      41, 2005) we purified several galectins and used them as tools for monitoring
      accessible binding sites. Herein, we report the use of galectin histochemistry
      for the analysis of diethylstilbestrol (DES)-induced renal tumors in male Syrian
      hamster kidney (SHKT). Sections of normal kidney and DES-treated kidney were
      analyzed with biotinylated galectins-1, -3 (full-length and truncated), and -7.
      Accessible binding sites were detected, localization was predominantly
      extracellular and confined to medium-sized and large tumors. Monitoring the SHKT
      derived HKT-1097 line, processed in vitro or as xenograft material, cytoplasmic
      and nuclear staining for galectins-1, -3, and -3tr could be observed. Adaptation
      of SHKT cells to long-term growth in culture is thus associated with emergence of
      this signal. Our data set illustrates the feasibility to complement
      immunohistochemical data by application of the tissue lectins as probes, and to
      detect regulation of galectin reactivity with differential characteristics within
      tumor progression in vivo and unique features of the tumor cell line in vitro and
      in vivo.

PMID- 16435124
TI  - Smooth muscle trans-membrane sarcoglycan complex in partial bladder outlet
      obstruction.
AB  - The urinary bladder experiences both distension and contraction as a part of the
      normal filling and emptying cycle. To empty properly, tension generated
      intracellularly in a smooth muscle cell must be smoothly and efficiently
      transferred across its sarcolemma to the basement membrane, which mediates its
      binding to both the extracellular matrix and to other cells. As a consequence of
      urethral obstruction, the bladder cannot generate appropriate force to contract
      the organ, thereby leading to inefficient emptying and associated sequelae. In
      this study, an animal model of urethral obstruction was utilized to study the
      membrane-associated structures that transfer tension across the sarcolemma of
      bladder smooth muscle cells. Immunohistochemical localization of key components
      of the smooth muscle tension transfer apparatus (TTA) was performed utilizing
      specific antibodies against:(1) the alpha-chains of type IV collagen, a basement
      membrane component, and (2) beta-sarcoglycan, an integral membrane protein that
      is a participant in the physical linkage between the cytoskeleton and the
      basement membrane. We demonstrate, in obstructed animals, that there is a
      pronounced disruption of the TTA with a physical displacement of these two
      components that can be demonstrated at the level of the light microscope using
      scanning confocal microscopy. Electron microscopy further demonstrates
      significant increases in the size of the junctional plaques between smooth muscle
      cells.

PMID- 16435125
TI  - Identification and characterization of stripe rust resistance gene Yr34 in common
      wheat.
AB  - An uncharacterized source of seedling resistance to Puccinia striiformis f.sp.
      tritici was identified in an advanced wheat breeding line WAWHT2046. Genetic
      analysis based on a WAWHT2046/Carnamah-derived double haploid (DH) population
      demonstrated monogenic inheritance of seedling stripe rust resistance in
      WAWHT2046. The gene controlling stripe rust resistance in line WAWHT2046 was
      tentatively designated YrWA. The chromosome 5AL located awn inhibitor gene B1,
      possessed by WAWHT2046, also showed monogenic inheritance when the DH population
      was scored for the presence and absence of awns. Joint segregation analysis at
      the B1 and YrWA loci indicated genetic linkage between the two loci. A
      recombination value of 12.2 cM was computed using Mapmanager. This association
      located YrWA in the chromosome arm 5AL. Molecular mapping using microsatellite
      markers placed YrWA distal to B1. All molecular markers mapped proximal to the
      awn inhibitor locus B1. As no other stripe rust resistance gene is reported to be
      located in the chromosome arm 5AL, YrWA was permanently designated as Yr34. Yr34
      produced an intermediate (23C) seedling infection type and expressed very low
      stripe rust response (10R-MR) on adult plants in the field, similar to the
      resistance gene Yr17. In addition to Yr34, this mapping population segregated for
      three genetically independent adult plant stripe rust resistance genes. The
      detection of DH lines with completely susceptible response, higher than that
      shown by the Yr34-lacking parent Carnamah, suggested that both parents
      contributed adult plant resistance. The use of WAWHT2046 as a parent in breeding
      programs would also contribute APR in addition to Yr34.

PMID- 16435126
TI  - Identification and molecular mapping of PdR1, a primary resistance gene to
      Pierce's disease in Vitis.
AB  - A major quantitative trait locus (QTL) controlling resistance to Pierce's disease
      (PD) of grape, caused by the bacterium Xylella fastidiosa (Xf), was identified on
      a Vitis linkage map and denoted as 'Pierce's disease resistance 1' (PdR1).
      Placement of the locus was accomplished by evaluating a family of full-sib
      progeny from a cross of two PD-resistant interspecific hybrids with resistance
      inherited from Vitis arizonica. Resistance was measured under greenhouse
      conditions by direct quantification of Xf numbers in stem tissues as well as by
      evaluation of disease symptoms based on leaf scorch and a cane maturation index
      (CMI). A large QTL (LOD 17.2) accounting for 72% of the phenotypic variance in
      bacterial numbers was localized to linkage group 14 of the male parent F8909-17.
      The approximate 95% confidence interval around the QTL peak extended 5.7 cM when
      using composite interval mapping. The other disease evaluation methods (leaf
      scorch and CMI, respectively) placed the resistance QTL to the same region on
      linkage group 14, although at wider 95% confidence intervals (6.0 and 7.5 cM),
      lower peak LOD scores (11.9 and 7.7) and accounting for less phenotypic variance
      (59 and 42%). This is the first report of an Xf resistance QTL mapped in any crop
      species. The relevance of the markers located in the region spanning the QTL will
      be discussed, addressing their usefulness for the development of PD-resistant
      grape cultivars.

PMID- 16435127
TI  - Hybrid maize breeding with doubled haploids: I. One-stage versus two-stage
      selection for testcross performance.
AB  - Optimum allocation of resources is of fundamental importance for the efficiency
      of breeding programs. The objectives of our study were to (1) determine the
      optimum allocation for the number of lines and test locations in hybrid maize
      breeding with doubled haploids (DHs) regarding two optimization criteria, the
      selection gain deltaG(k) and the probability P(k) of identifying superior
      genotypes, (2) compare both optimization criteria including their standard
      deviations (SDs), and (3) investigate the influence of production costs of DHs on
      the optimum allocation. For different budgets, number of finally selected lines,
      ratios of variance components, and production costs of DHs, the optimum
      allocation of test resources under one- and two-stage selection for testcross
      performance with a given tester was determined by using Monte Carlo simulations.
      In one-stage selection, lines are tested in field trials in a single year. In two
      stage selection, optimum allocation of resources involves evaluation of (1) a
      large number of lines in a small number of test locations in the first year and
      (2) a small number of the selected superior lines in a large number of test
      locations in the second year, thereby maximizing both optimization criteria.
      Furthermore, to have a realistic chance of identifying a superior genotype, the
      probability P(k) of identifying superior genotypes should be greater than 75%.
      For budgets between 200 and 5,000 field plot equivalents, P(k) > 75% was reached
      only for genotypes belonging to the best 5% of the population. As the optimum
      allocation for P(k)(5%) was similar to that for deltaG(k), the choice of the
      optimization criterion was not crucial. The production costs of DHs had only a
      minor effect on the optimum number of locations and on values of the optimization
      criteria.

PMID- 16435129
TI  - Substitution analog peptide derived from HER-2 can efficiently induce HER-2
      specific, HLA-A24 restricted CTLs.
AB  - In order to broaden the possibility for anti-HER-2/neu (HER-2) immune targeting,
      it is important to identify HLA-A24 restricted peptide epitopes derived from HER
      2, since HLA-A24 is one of the most common alleles in Japanese and Asian people.
      In the present study, we have screened HER-2-derived, HLA-A24 binding peptides
      for cytotoxic T lymphocyte (CTL) epitopes. A panel of HER-2-derived peptides with
      HLA-A24 binding motifs and the corresponding analogs designed to enhance HLA-A24
      binding affinity were selected. Identification of HER-2-reactive and HLA-A24
      restricted CTL epitopes were performed by a reverse immunology approach. To
      induce HER-2-reactive and HLA-A24 restricted CTLs, PBMCs from healthy donors were
      repeatedly stimulated with monocytes-derived, mature DCs pulsed with HER-2
      peptide. Subsequent peptide-induced T cells were tested for the specificity by
      enzyme linked immunospot, cytotoxicity and tetramer assays. CTL clones were then
      obtained from the CTL lines by limiting dilution. Of the peptides containing HLA
      A24 binding motifs, 16 peptides (nine mers) including wild type peptides (IC50
      <1,000 nM) and substituted analog peptides (IC50 <50 nM) were selected for the
      present study. Our studies show that an analog peptide, HER-2(905AA), derived
      from HER-2(905) could efficiently induce HER-2-reactive and HLA-A24 restricted
      CTLs. The reactivity of the HER-2(905AA)-induced CTL (CTL905AA) was confirmed by
      different CTL assays. The CTL905AA clones also were able to lyse HER-2(+), HLA
      A24(+) tumor cells and cytotoxicity could be significantly reduced in cold target
      inhibition assays using cold targets pulsed with the HER-2(905) wild type peptide
      as well as the inducing HER-2(905AA) analog peptide. A newly identified HER
      2(905) peptide epitope is naturally processed and presented as a CTL epitope on
      HER-2 overexpressing tumor cells, and an MHC anchor-substituted analog, HER
      2(905AA), can efficiently induce HER-2-specific, HLA-A24 restricted CTLs.

PMID- 16435128
TI  - Tumor immune escape mechanisms: impact of the neuroendocrine system.
AB  - Tumor cells act upon, and react to both their proximate and more distant
      environment, the mechanisms by which this is achieved being both autocrine and
      paracrine in nature. This interaction, however, takes place not only between
      adjacent malignant cells, but also non-malignant cells such as those of the
      immune system, the latter also partaking in the modeling of the tumor
      environment. Although tumor cells descend from normal tissue cells and thus bear
      in classical immunological terms 'self signals', it is evident that the immune
      system is able to recognize tumor cells as a harassment for the body and in
      consequence tries to eliminate these cells. On the counterpart, tumor cells
      acquire various characteristics which allow them to evade this immunological
      surveillance, and have been collectively coined with the term "tumor escape
      mechanisms". This review will describe and summarize current understanding of
      tumor escape strategies, and also more closely elaborate on the modulatory role
      of the neuroendocrine system in the immune system-tumor cell interaction.

PMID- 16435130
TI  - Costal exostosis presenting with hemothorax: report of one case.

PMID- 16435131
TI  - Management of hyperbilirubinemia and prevention of kernicterus in 20 patients
      with Crigler-Najjar disease.
AB  - We summarize the treatment of 20 patients with Crigler-Najjar disease (CND)
      managed at one center from 1989 to 2005 (200 patient-years). Diagnosis was
      confirmed by sequencing the UGTA1A gene. Nineteen patients had a severe (type 1)
      phenotype. Major treatment goals were to maintain the bilirubin to albumin
      concentration ratio at <0.5 in neonates and <0.7 in older children and adults, to
      avoid drugs known to displace bilirubin from albumin, and to manage temporary
      exacerbations of hyperbilirubinemia caused by illness or gallstones. A variety of
      phototherapy systems provided high irradiance over a large body surface. Mean
      total bilirubin for the group was 16+/-5 mg/dl and increased with age by
      approximately 0.8 mg/dl per year. The molar ratio of bilirubin to albumin ranged
      from 0.17 to 0.75 (mean: 0.44). The overall non-surgical hospitalization rate was
      0.12 hospitalizations per patient per year; one-half of these were for neonatal
      hyperbilirubinemia and the remainder were for infectious illnesses. Ten patients
      (50%) underwent elective laproscopic cholecystectomy for cholelithiasis. No
      patient required invasive bilirubin removal or developed bilirubin-induced
      neurological damage under our care. Visual acuity and color discrimination did
      not differ between CND patients and age-matched sibling controls. Four patients
      treated with orthotopic liver transplantation were effectively cured of CND,
      although one suffered significant transplant-related complications.Conclusions.
      While patients await liver transplantation for CND, hyperbilirubinemia can be
      managed safely and effectively to prevent kernicterus. Lessons learned from CND
      can be applied to screening and therapy of non-hemolytic jaundice in otherwise
      healthy newborns.

PMID- 16435132
TI  - Influence of the photoperiod on redox regulation and stress responses in
      Arabidopsis thaliana L. (Heynh.) plants under long- and short-day conditions.
AB  - Arabidopsis thaliana L. (Heynh.) plants were grown in low light (150 micromol
      photons m(-2) s(-1) and 20 degrees C) either in short days (7.5 h photoperiod) or
      long days (16 h photoperiod), and then transferred into high light and low
      temperature (350-800 micromol photons m(-2) s(-1) at 12 degrees C). Plants grown
      in short days responded with a rapid increase in NADP-malate dehydrogenase (EC
      1.1.1.82) activation state. However, persisting overreduction revealed a new
      level of regulation of the malate valve. Activity measurements and Northern-blot
      analyses indicated that NADP-malate dehydrogenase transcript and protein levels
      increased within a few hours. Using macroarrays, additional changes in gene
      expression were identified. Transcript levels for several enzymes of glutathione
      metabolism and of some photosynthetic genes increased. The cellular glutathione
      level increased, but its redox state remained unchanged. A different situation
      was observed in plants grown in long-day conditions. Neither NADP-malate
      dehydrogenase nor glutathione content changed, but the expression of several
      antioxidative enzymes increased strongly. We conclude that the endogenous systems
      that measure day length interact with redox regulation, and override the
      interpretation of the signals, i.e. they redirect redox-mediated acclimation
      signals to allow for more efficient light usage and redox poising in short days
      to systems for the prevention of oxidative damages when grown under long-day
      conditions.

PMID- 16435134
TI  - Strangulated umbilical hernias in children.
AB  - Umbilical hernia is a frequent pathology of the anterior abdominal wall in
      children. The hernia ring closes usually before 4 years, but a strangulation can
      occur. It is an exceptional complication according to the literature data. Since
      this complication is rare, we undertook a retrospective study of these
      strangulations in a 5-year period from January 1997 to December 2001 at Aristide
      Le Dantec hospital. We collected 41 cases that underwent emergency surgery
      operations for strangulated umbilical hernias, which represent about 15% of
      umbilical hernias operated during the same period. The age range was 8 months to
      10 years and the average age was 14 months. All the children were examined within
      24 h after the onset of the disease and the surgery was immediately performed. In
      five cases the bowel was necrosed and perforated and we performed a resection
      followed immediately by an anastomosis. In the follow up, two children presented
      wound infections and a hernia recurred in one child. There was no mortality. This
      study conducts us to question western reports which recommend conservative
      therapy for umbilical hernia in children.

PMID- 16435133
TI  - Infiltration of CD19+ plasma cells with frequent labeling of Ki-67 in
      corticosteroid-resistant active ulcerative colitis.
AB  - Abnormalities in humoral immunity are implicated in the pathogenesis of
      ulcerative colitis. However, the detailed mechanisms of B-cell activation in the
      locale remain unaccounted for. We analyzed ulcerative colitis from the standpoint
      of lymphocytic expansion in the loco. Intestinal specimens obtained at surgery
      from 30 patients with ulcerative colitis treated with corticosteroids and 15 with
      Crohn's disease were analyzed by immunohistochemistry and flow cytometry.
      Ulcerative colitis was characterized by a diffuse distribution of Ki-67(+) small
      round cells particularly in the ulcer base (that were CD19(+) and CD20(-)), with
      a significant number of them also CD138(+). Immunoelectron microscopy for CD19
      revealed an abundance of rough endoplasmic reticulum in the cytoplasm. These
      indicated that they are of immature plasma lineage cells. By contrast, plasma
      cells in Crohn's disease were negative for CD19, and the labeling for Ki-67 was
      infrequent, showing mature phenotype. Flow cytometry revealed an occurrence of
      CD19(+) and CD20(-) cells in ulcerative colitis but not in Crohn's disease. The
      labeling index of Ki-67 among CD19(+) plasma cells was positively correlated with
      the clinical activity of ulcerative colitis. High labeling of Ki-67 in CD19(+)
      plasma cells is specific for active ulcerative colitis that was resistant to
      medical treatment by corticosteroids.

PMID- 16435135
TI  - Differentiation between tuberculosis and primary tumors in the adrenal gland:
      evaluation with contrast-enhanced CT.
AB  - The aim of the present study is to determine imaging criteria for differentiating
      tuberculosis from primary tumors in the adrenal gland on contrast-enhanced CT.
      Non-contrast and contrast-enhanced CT features in 108 patients with adrenal
      tuberculosis (n = 34) and primary tumor (n = 74) were retrospectively assessed
      for the location, size, calcification and enhancement patterns. The primary
      tumors included 41 adenomas, 11 pheochromocytomas, 4 carcinomas, 3 lymphomas, 6
      myelolipomas, 6 ganglioneuromas, 2 neurilemmomas and 1 ganglioneuroblastoma.
      Biochemical investigation was performed for all patients. Of the tuberculosis
      cases, 31 (91%) invaded with bilateral involvement, while 7 (9%) of the primary
      tumors invaded with bilateral involvement (P < 0.001). Tuberculosis often showed
      calcification (20 of 34; 59%), whereas primary tumors infrequently showed
      calcification (6 of 74; 8%; P < 0.001). Low attenuation in the center with
      peripheral rim enhancement was more commonly seen in tuberculosis (16 of 34; 47%)
      than in primary tumors (7 of 74; 9%; P < 0.001). In the determination of
      tuberculosis, the highest sensitivity (91%) and accuracy (91%) were obtained with
      bilateral involvement, and the highest specificity (99%) was obtained with the
      contour preserved. In the determination of primary tumors using a combination of
      having unilateral involvement and being mass-like, the outcome was a sensitivity
      of 91%, specificity of 94% and accuracy of 92%. CT findings can differentiate
      tuberculosis from a primary tumor of the adrenal glands with high sensitivity and
      an acceptable specificity when combined with the endocrinological examination.

PMID- 16435136
TI  - Experimental and clinical evaluation of acromioclavicular joint structures with
      new scan orientations in MRI.
AB  - The objective of the study was to evaluate MRI for visualization of
      acromioclavicular (ac) joint structures in cadaveric shoulders, asymptomatic
      volunteers and symptomatic patients with trauma of the ac-joint. Three cadaveric
      shoulders were examined to find adequate planes and sequences for MRI.
      Afterwards, MR images were correlated to corresponding anatomical sections. Six
      asymptomatic volunteers and 13 patients were scanned in a 1.5 T Magnetom Vision
      with three sequences in the following planes: (1) parallel to the clavicle; (2)
      orthogonal to the ac joint, each time a fat-suppressed proton density-weighted +
      T2-sequence (TR/TE 4,000/15 ms) was performed; (3) parallel to the clavicle, T1
      SE (TR/TE 817/20 ms). The parameters were: slice thickness 3 mm, field-of-view
      180 mm, matrix 210x256 pixels. Standard of reference in the patients was clinical
      examination and conventional X-rays. Classification was by Rockwood grades I-VI.
      MRI allowed excellent visualization and diagnoses of ac-joint structures in
      volunteers and patients (n=6 normal, n=1 Rockwood I, n=5 Rockwood II, n=3
      Rockwood III, n=4 Rockwood V). On MRI, in one lesion type II and III each, a
      lower lesion type was suspected clinically and by X-ray. In one patient
      additional information by MRI led to surgery. MRI allows excellent anatomical
      display of ac-joint structures and can give clinically relevant information on
      type and extension of ac-joint trauma, which may influence therapy.

PMID- 16435137
TI  - MR imaging of autologous chondrocyte implantation of the knee.
AB  - Autologous chondrocyte implantation (ACI) is a surgical technique that is
      increasingly being used in the treatment of full-thickness defects of articular
      cartilage in the knee. It involves the arthroscopic harvesting and in vitro
      culture of chondrocytes that are subsequently implanted into a previously
      identified chondral defect. The aim is to produce a repair tissue that closely
      resembles hyaline articular cartilage that gradually becomes incorporated,
      restoring joint congruity. Over the long term, it is hoped that this will prevent
      the progression of full-thickness articular cartilage defects to osteoarthritis.
      This article reviews the indications and operative procedure performed in ACI.
      Magnetic resonance imaging (MRI) sequences that provide optimal visualization of
      articular cartilage in the post-operative period are discussed. Normal
      appearances of ACI on MRI are presented along with common complications that are
      encountered with this technique.

PMID- 16435138
TI  - Long-term effects of percutaneous nephrolithotomy on renal morphology and
      arterial vascular resistance as evaluated by color Doppler ultrasonography:
      preliminary report.
AB  - We evaluated the long-term effects of percutaneous nephrolithotomy (PNL) on renal
      morphology and vascular resistance. Parenchyma thickness, echogenicity and
      resistive index (RI) of upper, middle and lower poles of operated and
      contralateral kidneys of 41 patients with 82 renal units who underwent unilateral
      PNL with single pole access between 2000 and 2002 were examined separately by
      color Doppler ultrasonography. Mean patient age and duration between PNL and
      evaluation time were 38.29+/-11.53 years and 46.44+/-10.9 months, respectively.
      In operated kidney, mean RI, parenchyma thickness and echogenicity of the access
      pole were not statistically different than those of the adjacent two poles
      (0.608+/-0.053 vs. 0.608+/-0.052 for RI, P=0.895; 11.46+/-2.58 vs. 11.41+/-2.68
      mm for parenchyma thickness, P=0.838; 0.049+/-0.31 vs. 0.073+/-0.33 for
      parenchyma echogenicity, P=0.160, respectively). Although mean RI and parenchyma
      thickness of access pole were statistically significantly different than the mean
      values of contralateral kidney (0.562+/-0.032 and 14.31+/-1.37 mm, respectively),
      no statistical difference was found between mean parenchyma echogenicities of
      both of them (echogenicity of contralateral kidney was 0, P=0.317). No
      significant difference was found between the average echogenicities of the three
      poles of the operated and contralateral kidneys (0.063+/-0.32 vs. 0, P=0.080). In
      14 patients RI decreased from 0.694+/-0.058 to 0.602+/-0.056 in operated kidney
      (P=0.001) and from 0.604+/-0.06 to 0.559+/-0.031 in contralateral kidney
      (P=0.018) following PNL. It seems that PNL does not cause renal scarring, renal
      parenchymal loss or increase in renal vascular resistance in the long term.
      However, prospective studies must be performed for more definitive conclusions.

PMID- 16435139
TI  - Debate: the key to stone formation is ...

PMID- 16435140
TI  - Imaging findings in subcutaneous fat necrosis in a newborn.
AB  - We describe the ultrasonography, the contrast-enhanced computed tomography and
      the magnetic resonance imaging of subcutaneous fat necrosis in a newborn infant.

PMID- 16435141
TI  - Detection of bone marrow micrometastasis and microcirculating disease in
      rhabdomyosarcoma by a real-time RT-PCR assay.
AB  - PURPOSE: To assess if molecular detection of minimal disseminated disease by real
      time reverse transcription and polymerase chain reaction (RT-PCR) could
      contribute to a better treatment stratification in patients with rhabdomyosarcoma
      (RMS). METHODS: Relative quantification of the tumor-mRNA present in serial
      samples of bone marrow (BM) and peripheral blood (PB) from 16 patients with RMS
      (7 alveolar and 9 embryonal) was performed by a real-time RT-PCR assay.
      Expression of MyoD1 and acetylcholine receptor (AChR) was analyzed in all
      samples, along with PAX3/7-FKHR in samples from alveolar tumors. RESULTS: A good
      correlation was found between the expression of PAX3/7-FKHR and AChR, while MyoD1
      was more sensitive but less specific. In this study, patients with positive PB at
      the end of treatment showed a poorer prognosis than patients with negative PB.
      Moreover, in this patient cohort, metastatic relapses were preceded by the
      detection of microcirculating disease in all cases. CONCLUSION: The detection of
      minimal circulating and micrometastatic disease by real-time RT-PCR, based on the
      expression of multiple genes, yields highly reproducible results. Patients with
      positive PB after treatment show poorer survival than patients without
      microcirculating disease.

PMID- 16435142
TI  - Trends in endocrine therapy and chemotherapy for early breast cancer: a focus on
      the premenopausal patient.
AB  - PURPOSE: The majority of breast cancers are diagnosed at an early stage, and
      treatment is focused on cure and prolonging disease-free survival. Local therapy
      (surgery and/or radiation treatment) is standard, along with systemic adjuvant
      therapy that may effectively prevent or delay relapse and death in early-stage
      disease. In premenopausal women, adjuvant therapeutic approaches include
      combination cytotoxic chemotherapy and endocrine therapy. Cyclophosphamide,
      methotrexate and 5-fluorouracil (CMF) was the established chemotherapy regimen;
      however, newer regimens have more recently been introduced that may offer some
      benefit over CMF including anthracycline-containing regimens [e.g.
      cyclophosphamide, epirubicin and 5-fluorouracil (CEF)], and taxane-containing
      regimens. For women with oestrogen receptor (ER)-positive disease, a second
      option is endocrine therapy that aims to suppress mitogenic oestrogen signalling.
      Until recently, 5 years of tamoxifen was regarded as the standard adjuvant
      endocrine treatment in ER-positive disease. Ovarian ablation is also effective in
      premenopausal women, and can be achieved by surgery, radiotherapy, or via the use
      of a luteinising hormone-releasing hormone analogue such as goserelin. Combining
      tamoxifen and goserelin treatment provides more effective oestrogen blockade than
      either drug alone. However, as the third-generation aromatase inhibitors (AIs)
      have demonstrated improved efficacy over tamoxifen in postmenopausal women with
      early and advanced disease, combination treatment with goserelin plus an AI may
      provide optimal oestrogen blockade in premenopausal patients. CONCLUSIONS: This
      review assesses the relative merits of chemotherapeutic and endocrine approaches
      for the treatment of early breast cancer, and summarises relevant ongoing
      clinical trials, with an emphasis on the premenopausal setting.

PMID- 16435143
TI  - Epirubicin, cyclophosphamide and weekly paclitaxel as neoadjuvant chemotherapy
      for stage II and III breast cancer.
AB  - PURPOSE: To assess the efficacy and the toxicity of a new combination of
      epirubicin, cyclophosphamide and paclitaxel as neoadjuvant chemotherapy for
      breast cancer. METHODS: Patients with stage II and III breast cancer received 3-4
      cycles of epirubicin 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) on day 1, and
      paclitaxel at a dose of 100 mg on days 1, 8, 15 and 22 on a 28-day cycle.
      RESULTS: Forty-nine patients were enrolled in the study. Stage II was present in
      16 patients (32.7%) and stage III in 33 patients (67.3%). Relevant toxicities
      were nausea/vomiting grades III-IV in 6 patients (12.2%) and neutropenia grade
      III-IV in 33 patients (67.3%). The overall clinical response rate was 83.7%.
      Partial response was observed in 25 patients (51%), complete response in 16
      patients (32.7%), stable disease in 7 patients (14.3%) and progression in 1
      patient. Thirty-three non-inflammatory breast cancer patients underwent surgery,
      29 with breast-conserving surgery (87.9%). Pathological complete response was
      found in 5 patients (15.1%). CONCLUSIONS: The combination of epirubicin,
      cyclophosphamide and weekly paclitaxel as given in this study is safe and shows
      good activity in the neoadjuvant setting of stage II and III breast cancer
      patients.

PMID- 16435144
TI  - Acrokeratosis paraneoplastica of Bazex as an indicator for underlying squamous
      cell carcinoma of the lung.
AB  - PURPOSE: Obligatory cutaneous paraneoplastic disorders comprising acanthosis
      nigricans maligna, erythema gyratum repens, paraneoplastic pemphigus,
      hypertrichosis lanuginosa acquisita, erythema necrolyticum migrans and
      acrokeratosis paraneoplastica are rare. However, as markers of an underlying
      internal malignancy they are of utmost importance for the patient. Acrokeratosis
      paraneoplastica (first described by Gougerot and Rupp in 1922) was named after
      Bazex who had then reported several cases in a French dermatological journal
      since 1965 (Bazex et al. in Bull Soc Fr Dermatol Syphiligr 72:182, 1965; Bazex
      and Griffiths in Br J Dermatol 102:301-306, 1980). METHOD: The study is a
      clinical case of a patient with acrokeratosis paraneoplastica. RESULTS: the
      patient was later diagnosed with a cervical lymph node metastasis and thereafter
      with a primary squamous cell carcinoma of the left upper lobe and upon treatment
      responded with the clearing of the skin changes. CONCLUSION: Identification of a
      paraneoplastic syndrome may enhance the earlier diagnosis of the associated tumor
      and may thus enable curative treatment.

PMID- 16435145
TI  - The seventh Korea-Japan joint symposium on cancer and ageing research: molecular
      targets in cancer and ageing research.

PMID- 16435146
TI  - Retroperitoneoscopic donor nephrectomy: donor outcome and complication rate in
      comparison with three different techniques.
AB  - Four surgical techniques for living donor nephrectomy were analyzed
      retrospectively in terms of perioperative outcome and early complication rate. A
      total of 182 donor nephrectomies including 69 open (OLDN), 14 fully laparoscopic
      (LDN), 34 hand-assisted laparoscopic (HLDN) and 65 retroperitoneoscopic (RLDN)
      nephrectomies were analyzed. There was a significant difference in mean operating
      time (OPT) between the OLDN (160 min) and RLDN (150 min) as compared to the LDN
      (212 min) and HLDN group (192 min) (P < 0.001). Mean warm ischemia time (WIT) was
      significantly shorter with OLDN (114 s), RLDN (121 s) and HLDN (128 s) when
      compared to LDN (238 s) (P < 0.001). Major complication rate was comparable among
      the groups. Independent of the preferred technique, donor nephrectomy is
      associated with complication rates. RLDN is comparable to OLDN in terms of OPT,
      WIT. Learning endoscopic donor nephrectomy could be associated with a higher
      complication rate.

PMID- 16435147
TI  - Intra-operative inferior vena cava syndrome in a patient with autosomal dominant
      polycystic kidney disease.
AB  - The renal and hepatic cysts characteristic of autosomal dominant polycystic
      kidney disease can exert a mass effect on surrounding structures. If this
      involves the inferior vena cava (IVC), patients usually present with signs and
      symptoms characteristic of congestive heart failure. However, the absence of
      these signs or symptoms does not exclude a potentially hemodynamically
      significant IVC syndrome. This case report describes a patient with no pre
      operative evidence of congestive heart failure or IVC compression, who
      subsequently experienced intra-operative hypotension and hypoxemia due to an IVC
      syndrome.

PMID- 16435148
TI  - Ilizarov treatment of complex tibial pilon fractures.
AB  - We treated 21 consecutive patients between 1998 and 2002 with complex tibial
      pilon fractures, eight type B and 13 type C, using percutaneous reduction and
      fixation with the small diameter Ilizarov apparatus. The average patient age was
      34+/-5.6 years (range 28-52 years). Nine of the patients had open fractures (two
      type I, four type II, and three type IIIA). The patients were followed up
      regularly at 6-month intervals for 2 years. All fractures united. The fixator was
      removed at an average of 26.6+/-4.2 weeks (range 20-34 weeks). The average
      American Orthopaedic Foot and Ankle Society ankle-hind foot score was excellent
      in 11 patients, good in five, fair in four, and poor in one. Thirteen patients
      were able to squat and climb stairs.

PMID- 16435149
TI  - Osteoarthritis after anterior cruciate ligament reconstruction using a patellar
      tendon autograft.
AB  - We studied 58 knees that underwent anterior cruciate ligament (ACL)
      reconstruction using a patella tendon autograft. The mean age at reconstruction
      was 30.4 (18-58) years, and the average follow-up was 11.2 (8.6-13.8) years. The
      presence of osteoarthritis was assessed radiographically using Kellgren and
      Lawrence's classification. Osteoarthritis was detected in the medial compartment
      in 25 cases and in the lateral compartment in 14 cases. Significant independent
      predictors of osteoarthritis were: accompanying meniscal injury [odds ratio (OR)
      9.19), p<0.001], an interval of more than 6 months from injury to reconstruction
      (OR 4.77, p=0.021), and age more than 25 years at reconstruction (OR 3.37,
      p=0.034). However, no statistically significant correlation was found between the
      development of osteoarthritis and clinical outcome or radiological stability.

PMID- 16435150
TI  - Prevalence of degenerative joint complaints of the lower extremity: a
      representative study.
AB  - As part of the international campaign of the bone and joint decade, we aimed to
      present epidemiological data on the prevalence of major joint complaints in a
      Central European region. Ten thousand subjects aged between 14 and 65, selected
      randomly by the Hungarian central office of statistics from three counties in
      southern Hungary, were surveyed using our own questionnaire based on widely
      accepted scoring systems in the literature, focusing on major degenerative joint
      complaints, and using the short form 36 (SF-36) questionnaire. We found that the
      prevalence of hip pain in the observed group was 22.2%, the prevalence of knee
      pain 30.3%, and frequent ankle pain occurred in 9.7%. The results of the SF-36
      questionnaire showed that with the exception of social function, neither of the
      values of the examined health dimensions reached levels of other international
      surveys. Details of the survey and the possible causes of the higher prevalence
      are discussed, along with the results of the SF-36 questionnaire.

PMID- 16435151
TI  - Acute blood neutrophilia induced by short-term compost dust exposure in
      previously unexposed healthy individuals.
AB  - OBJECTIVES: Systemic effects of organic dust inhalation have been described in
      farming environments. The purpose of this study was to examine whether a single
      exposure at a biowaste composting facility could also exert systemic effects in
      healthy volunteers not previously exposed to organic dust from such facilities.
      METHODS: Seventeen subjects (age 20-35 years) were exposed to organic dust for 2
      h (exposure day) during moderate exercise; 12 of these subjects also took part in
      a control experiment (control day). Spirometry was performed before and
      immediately after the exposure. White blood cell counts and levels of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6
      (IL-6) in peripheral blood were determined before and 3 h after exposure.
      RESULTS: Exposures did not result in significant changes in lung function or
      blood cytokine levels. In contrast, the number and percentage of neutrophils
      increased during the exposure day [median (range) percent change of percentages
      14 (-2; 67) %; P=0.002], but not during the control day [5 (-22; 35) %; P=0.66).
      Furthermore, there was a decrease in the number and percentage of eosinophils
      during the exposure day [-47 (-57; 0.0) %; P=0.002], whereas the change during
      the control day was smaller [-8 (-56; 71) %; P=0.68]. CONCLUSION: Short-term
      exposure of healthy, young subjects to organic dust from composting facilities
      had opposite effects on the numbers of blood neutrophils and blood eosinophils.
      These effects, though mild, suggest that even during a limited period of moderate
      work a sufficient amount of bioactive material can be deposited in the lung to
      elicit acute systemic alterations.

PMID- 16435152
TI  - Interactions of skin thickness and physicochemical properties of test compounds
      in percutaneous penetration studies.
AB  - OBJECTIVES: To determine the effect of skin thickness on the percutaneous
      penetration and distribution of test compounds with varying physicochemical
      properties using in vitro systems. Studies were carried out in accordance with
      OECD guidelines on skin absorption tests. METHODS: Percutaneous penetration of
      caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite
      dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted
      finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of
      varying thicknesses under occluded conditions was measured using flow through
      cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with
      BSA added for studies with testosterone and propoxur. Following exposure, the
      remaining surface dose was removed by swabbing and the skin digested prior to
      scintillation counting. RESULTS: The maximum flux of caffeine was increased with
      decreasing skin thickness, although these differences were found to be non
      significant. The presence of caffeine in the skin membrane was not altered by
      skin thickness. Maximum flux and cumulative dose absorbed of testosterone and
      butoxyethanol (in both finite and infinite doses) were markedly reduced with full
      thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5
      mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher
      through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found
      between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane
      after 24 h increased significantly over the complete range of thicknesses tested
      (0.56-1.36 mm). CONCLUSIONS: A complex relationship exists between skin
      thickness, lipophilicity and percutaneous penetration and distribution. This has
      implications for risk assessment studies and for the validation of models with
      data from different sources.

PMID- 16435153
TI  - Olfactory toxicity: long-term effects of occupational exposures.
AB  - OBJECTIVE: To present and discuss the results of research on olfactory function
      impairments related to chronic occupational exposure to industrial chemicals.
      METHODS: This review is mainly focused on the results of epidemiological studies
      on olfactory function, evaluated using quantitative testing methods, in workers
      chronically exposed to airborne industrial chemicals. Papers published in peer
      reviewed scientific journals were mainly considered. RESULTS: The prevalence of
      olfactory impairments related to occupational exposure to chemicals is unknown:
      frequencies ranging 0.5-5% of all olfactory dysfunctions have been proposed,
      considering both exposure to chemicals and the use of pharmaceutical drugs, but
      the real relevance of this problem is possibly overlooked, especially considering
      that occupational exposure may account for a significant part of "idiopathic"
      smell disorders, i.e., the 10-25% of all olfactory problems within the general
      population. An adverse effect has been reported in workers chronically exposed to
      some metals as cadmium, chromium, manganese, arsenic, mercury, and organic lead,
      and to other chemicals as acrylates, styrene, and solvent mixtures. The results
      of relevant studies are discussed. A problem in the evaluation of data is that
      different methods have been applied in different studies, affecting the
      comparability of results. CONCLUSIONS: To date, knowledge of the effect of
      chronic occupational exposure to industrial chemicals on olfactory function is
      largely incomplete, but supports the hypothesis that olfactory neuroepithelium is
      susceptible to environmental exposures to chemicals. Occupational-related
      olfactory impairment is usually sub-clinical, and can be only detected using
      adequate quantitative olfactory function testing procedures. Available data show
      the need for further good quality research in this field.

PMID- 16435154
TI  - Additive antitumor effects of gefitinib and imatinib on anaplastic thyroid cancer
      cells.
AB  - PURPOSE: Anaplastic thyroid cancer (ATC) is one of the most aggressive
      malignancies. Although multidisciplinary treatments have been introduced,
      patients with this disease rarely survive longer than 1 year. These findings
      prompted us to investigate the antitumor activity of molecular targeting agents
      in thyroid cancer cells. METHODS: Two tyrosine kinase inhibitors, gefitinib and
      imatinib, were tested in a poorly differentiated thyroid cancer cell line, KTC-1,
      and two ATC cell lines, KTC-2 and KTC-3. RESULTS: All cell lines expressed not
      only a target molecule of gefitinib, HER1, but also a cognate receptor, HER2.
      They also expressed target molecules of imatinib, c-ABL and platelet-derived
      growth factor receptors at various levels. Both agents had modest antitumor
      activity in these cell lines. Combined treatment with gefitinib and imatinib led
      to an additional antitumor effect. Each agent induced apoptosis and their
      combined treatment enhanced apoptosis associated with the down-regulation of
      antiapoptotic proteins, Bcl-2 and Bcl-xL. Moreover, their combined treatment
      additionally inhibited the growth of KTC-3 xenografts in nude mice. CONCLUSIONS:
      These are the first findings to suggest that both gefitinib and imatinib have
      antitumor activity against ATC cells and that their combined use has greater
      activity than either drug alone.

PMID- 16435155
TI  - Trichostatin A sensitizes TRAIL-resistant myeloma cells by downregulation of the
      antiapoptotic Bcl-2 proteins.
AB  - PURPOSE: In this study, we have investigated the effect of trichostatin A (TSA)
      pretreatment on the cytotoxicity of TRAIL in TRAIL-resistant myeloma cells.
      METHODS AND RESULTS: MM1S myeloma cells exhibited resistance to TRAIL-induced
      apoptosis even at high doses of TRAIL and was sensitive to low doses of TSA.
      Sequential treatment of myeloma cells with TSA followed by TRAIL enhanced TRAIL
      cytotoxicity. TSA induced the transcription of TRAIL death receptor DR5 without
      affecting the transcription of DR4 and the decoy receptors; DcR1 and DcR2.
      However, the surface expression of both DR4 and DR5 was not modulated by TSA
      treatment. TSA treatment repressed the transcription and downregulated the
      expression of the antiapoptotic Bcl-2 proteins; Bcl-2 and Bcl-XL. Surprisingly,
      the effect of TSA on the proapoptotic Bcl-2 proteins was mixed, the two isoforms
      of PUMA (alpha, beta), Noxa, Bax were downregulated, while Bim was upregulated.
      Although MM1S cells showed higher expression level of FLIP(S) than other TRAIL
      sensitive myeloma cells, the enhancing effect of TSA was not accompanied by
      FLIP(S) downregulation. CONCLUSION: In conclusion, TSA sensitized TRAIL-resistant
      myeloma cells by downregulating the antiapoptotic Bcl-2 protein without altering
      FLIP(S) expression.

PMID- 16435156
TI  - FK228 (depsipeptide): a HDAC inhibitor with pleiotropic antitumor activities.
AB  - PURPOSE: The fundamental role of epigenetic events in carcinogenesis has resulted
      in the evolution of epigenetic targeting as a new paradigm in anticancer
      therapeutics. Aberrant histone deacetylase (HDAC) activity has been documented in
      many human malignancies resulting in the repression of tumor suppressor genes and
      promotion of tumorigenesis. FK228, also known as depsipeptide, is a novel,
      natural, bicyclic tetrapeptide with significant antitumor properties which are
      mostly mediated by inhibition of HDACs. RESULTS: FK228 induces the expression of
      genes linked to the inhibition of cell growth, induction of cell differentiation,
      promotion of apoptotic cell death and inhibition of angiogenesis. CONCLUSION: Its
      multitargeting properties, its ability to act on non-histone targets, its
      clinical activity and its acceptable side-effect profile render FK228 a very
      promising novel anticancer agent.

PMID- 16435157
TI  - Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents.
AB  - PURPOSE: Chemotherapy treatment may lead to delayed gastric emptying, early
      satiety, anorexia, nausea and vomiting, described collectively as the cancer
      associated dyspepsia syndrome (CADS). METHOD: We examined the effects of ghrelin
      in rodent models of CADS induced by treatment with cisplatin. RESULTS: In rats,
      increased gastric contents and reduced feeding were observed 48 h after injection
      with cisplatin (6 mg/kg, i.p.). Ghrelin (0.5 mg/kg, i.p.) caused a 16-fold
      increase in food intake over 1 h in cisplatin/ghrelin-treated rats compared to
      cisplatin/vehicle-treated rats. A single dose of ghrelin also restored the
      decreased locomotor activity in rats induced by cisplatin to almost the same
      level of saline-treated rats. In mice, daily food intake was significantly
      decreased at 24 h (60%) and 48 h (74%) after cisplatin (20 mg/kg, i.p.). Ghrelin
      (1 mg/kg, i.p.x2) significantly increased food intake measured at the 48 h time
      point in both saline/ghrelin-treated and cisplatin/ghrelin-treated mice, with
      this effect being most marked in the cisplatin-treated group, where a twofold
      increase in feeding was observed. In cisplatin-treated mice, delayed gastric
      emptying was indicated by a 7.7-fold increase in the wet weight of gastric
      contents and ghrelin improved the gastric emptying index (GEI) by 31% (P < 0.01).
      CONCLUSION: Together, these results suggest that it is possible to model cancer
      chemotherapy-induced dyspepsia in rodents and that ghrelin can greatly alleviate
      the behaviours associated with this syndrome. Agonists at the ghrelin receptor
      may, therefore, become a useful human therapeutic for this disorder.

PMID- 16435158
TI  - Sleep in acute care units.
AB  - Patients in the acute care units (ACU) are usually critically ill, making them
      more susceptible to the unfavorable atmosphere in the hospital. One of these
      unfavorable factors is sleep disruption and deprivation. Many factors may affect
      sleep in the ACU, including therapeutic interventions, diagnostic procedures,
      medications, the underlying disease process, and noise generated in the ACU
      environment. Many detrimental physiological effects can occur secondary to noise
      and sleep deprivation, including cardiovascular stimulation, increased gastric
      secretion, pituitary and adrenal stimulation, suppression of the immune system
      and wound healing, and possible contribution to delirium. Over the past few
      years, many studies have endeavored to objectively assess sleep in the ACUs, as
      well as the effect of mechanical ventilation and circadian rhythm changes
      critically ill patients. At this time, therefore, it is important to review
      published data regarding sleep in ACUs, in order to improve the knowledge and
      recognition of this problem by health care professionals. We have therefore
      reviewed the methods used to assess sleep in ACUs, factors that may affect sleep
      in the ACU environment, and the clinical implications of sleep disruption in the
      ACU.

PMID- 16435160
TI  - Morbidity and mortality of patients diagnosed with systemic sclerosis after the
      age of 75: a nested case-control study.
AB  - This study aims to characterize the clinical features of a cohort of patients
      diagnosed with systemic sclerosis (SSc) after the age of 75 and compare them to a
      group diagnosed at a younger age. We record the review of 769 patients diagnosed
      with SSc over the past 16 years. Utilizing a nested case-control model, we
      compare demographics, disease severity, morbidity, and mortality data of all
      patients diagnosed after the age of 75 to sex- and disease-type-matched, randomly
      selected group of patients diagnosed with SSc before the age of 60. Twelve
      patients were diagnosed with SSc after the age of 75, seven with the diffuse, and
      five with the limited form. It took longer to diagnose SSc in the older patients,
      and comparison of disease severity revealed a worse pulmonary picture and a more
      frequent development of malignancy in the older patients as compared with the
      younger ones. During a mean follow-up of 36.2 months, our cohort of patients did
      not have worsening in their disease severity, though 6 months after the last
      follow-up, six patients died. We conclude that a diagnosis of SSc at an older age
      appears to be a poor prognostic indicator related to both disease severity and
      comorbidities. A higher clinical suspicion will lead to an earlier diagnosis and
      a potential decrease in morbidity and mortality.

PMID- 16435159
TI  - Thrombotic manifestations of the antiphospholipid syndrome in patients with
      malignancies.
AB  - The presence of antiphospholipid antibodies has been reported in a large variety
      of patients with malignancies. Many case reports and reviews have appeared
      indicating that the presence of the antiphospholipid antibodies is related to
      thrombotic associations with the antiphospholipid syndrome (APS) in a proportion
      of these patients. We investigated the frequency of the thrombotic manifestations
      in 58 patients demonstrating antiphospholipid antibodies and with a history of
      neoplasia, including haematologic and lymphoproliferative malignancies.
      Antiphospholipid antibodies were detected by clotting assay [lupus anticoagulant
      (LAC)] or by enzyme-linked immunosorbent assay [anticardiolipin antibodies (aCL)]
      according to the Sapporo criteria. Patients, 39/58, suffered from solid tumours
      and 19/58 patients from malignant haematologic or lymphoproliferative diseases.
      One patient was suffering simultaneously from two solid tumours and a malignant
      lymphoma. Among the patients with solid tumours, 18/39 (46%) patients had
      thromboembolic complications of the antiphospholipid syndrome. Among the patients
      with haematologic and lymphoproliferative malignancies, only 6/19 (32%) suffered
      from thromboembolic complications. There was, however, no relation between the
      titres of aCL antibodies and the clinical manifestations. The presence, but not
      the titres, of antiphospholipid antibodies may identify a subset of cancer
      patients with a high risk of developing thrombotic complications. The frequency
      of thrombosis, however, is lower in aPL-positive patients with
      lymphoproliferative and haematological malignancies.

PMID- 16435161
TI  - Inheritance of behavioral and neuroanatomical phenotypical variance: hybrid mice
      are not always more stable than inbreds.
AB  - Many investigators have attempted to confirm the prediction that increased levels
      of heterozygosity entail greater developmental stability, manifesting itself
      through decreased phenotypical variation. The evidence presented so far is
      equivocal. The predicted relationship has been found in some morphological
      studies, but not in others. I propose that the variability of a character should
      be seen as different from the character itself. For most morphological
      characters, natural selection promotes strong canalization of development but, to
      facilitate responses to environmental changes, the organism needs to retain
      malleability of physiological and behavioral traits. These different types of
      selection should lead to distinct genetic architectures for these phenotypes. I
      report on the results of a diallel cross between four inbred mouse strains.
      Qualitatively different genetic architectures were in fact revealed for variation
      in behaviors in the open-field. In a second study, variances of inbred and hybrid
      populations for hippocampal morphometry were studied. Again, hybrids were not
      always less variable than inbreds and sometimes even more variable. It follows
      that there exists no one-to-one relation between heterozygosity and developmental
      stability.

PMID- 16435164
TI  - Granulocyte-macrophage colony-stimulating factor for perianal hidradenitis
      suppurativa: report of a case.
AB  - Perianal hidradenitis suppurativa is a chronic inflammatory disease associated
      with significantly high morbidity, which severely affects the quality of life of
      those patients suffering from it. We describe a 46-year-old patient with
      extensive, severe gluteal and perianal PHS of 28 years duration. Repeated wide
      excisions, fistulotomies, treatments with hyperbaric oxygen, and finally a
      diverting colostomy were unsuccessful. A new form of treatment with repeated
      perilesional injections of granulocyte-macrophage colony-stimulating factor, in
      conjunction with surgical procedures, was performed with excellent results.

PMID- 16435165
TI  - Postsurgical adhesion prevention.

PMID- 16435166
TI  - First 100 cases with Doppler-guided hemorrhoidal artery ligation.
AB  - PURPOSE: This study was designed to examine the benefits of a Doppler-guided
      hemorrhoidal artery ligation technique in terms of surgical outcome, functional
      recovery, and postoperative pain. METHODS: Using local, regional, or general
      anesthesia, 100 patients with symptomatic Grades II or III hemorrhoids underwent
      sonographic identification and suture ligation of six to eight terminal branches
      of the superior rectal artery above the dentate line. Visual Analog Scales were
      used for postoperative pain scoring. Surgical and functional outcomes were
      assessed at 6 weeks and 3, 6, and 12 months after surgery. RESULTS: There were 42
      (42 percent) males and 58 (58 percent) females (mean age, 42 years; median
      duration of symptoms, 6.3 years). The mean operative time was 19 minutes. Local
      anal block combined with intravenous sedation (n = 93) or general or spinal (n =
      7) anesthesia was used. Only five were hospitalized overnight. There was no
      urinary retention, bleeding, or mortality in the immediate postoperative course.
      The mean pain score decreased from 2.1 at two hours postoperative to 1.3 on the
      first postoperative day. All patients had a complete functional recovery by the
      third postoperative day. Ninety-four patients remained asymptomatic after a mean
      follow-up of six months: four patients required additional surgical excision, and
      two required rubber band ligations for persistent bleeding. On follow-up, there
      was no report of incontinence to gas or feces, fecal impaction, or persistent
      pain. CONCLUSIONS: Our experience indicates that Doppler-guided hemorrhoidal
      artery ligation is safe and effective and can be performed as an outpatient
      procedure with local or regional anesthesia and with minimal postoperative pain
      and early recovery.

PMID- 16435168
TI  - Effect of nutrient loading on bacterioplankton community composition in lake
      mesocosms.
AB  - Changes in bacterioplankton community composition were followed in mesocosms set
      up in the littoral of Lake Vesijarvi, southern Finland, over two summers.
      Increasing nitrogen and phosphorus concentrations in the mesocosms represented
      different trophic states, from mesotrophic to hypertrophic. In 1998, the
      mesocosms were in a turbid state with a high biomass of phytoplankton, whereas in
      1999, macrophytes proliferated and a clear-water state prevailed. The bacterial
      communities in the mesocosms also developed differently, as shown by denaturing
      gradient gel electrophoresis profiling of partial 16S rRNA gene fragments and by
      nonmetric multidimensional scaling analysis. In 1998, nutrient treatments
      affected the diversity and clustering of bacterial communities strongly, but in
      1999, the bacterial communities were less diversified and not clearly affected by
      treatments. Canonical correspondence analysis indicated that bacterioplankton
      communities in the mesocosms were influenced by environmental physicochemical
      variables linked to the increasing level of eutrophication. Nitrogen
      concentration correlated directly with the bacterioplankton composition. In
      addition, the high nutrient levels had indirect effects through changes in the
      biomass and composition of phyto- and zooplankton. Sequencing analysis showed
      that the dominant bacterial divisions remained the same, but the dominant
      phylotypes changed during the 2-year period. The occurrence of Verrucomicrobia
      correlated with more eutrophic conditions, whereas the occurrence of
      Actinobacteria correlated with less eutrophic conditions.

PMID- 16435167
TI  - Two-component signal transduction systems, environmental signals, and virulence.
AB  - The relevance toward virulence of a variety of two-component signal transduction
      systems is reviewed for 16 pathogenic bacteria, together with the wide array of
      environmental signals or conditions that have been implicated in their
      regulation. A series of issues is raised, concerning the need to understand the
      environmental cues that determine their regulation in the infected host and in
      the environment outside the laboratory, which shall contribute toward the
      bridging of bacterial pathogenesis and microbial ecology.

PMID- 16435169
TI  - Toxic Microcystis is widespread in Lake Erie: PCR detection of toxin genes and
      molecular characterization of associated cyanobacterial communities.
AB  - During the past decade, algae blooms, which include the toxic cyanobacterium
      Microcystis, have reoccurred in the Laurentian Great Lakes, most commonly in the
      western basin of Lake Erie. Whereas the western basin is the most impacted by
      toxic Microcystis in Lake Erie, there has historically been little effort focused
      on identifying the spatial distribution of Microcystis throughout this lake. To
      address this lack of knowledge, we have employed a polymerase-chain-reaction
      based detection of genes required for synthesis of the toxin microcystin (mcyD
      and mcyB), as well as 16S rDNA fragments specific to either all Microcystis or
      all cyanobacteria. Using a multiplex approach, we tested 21 samples from 13 field
      stations and found that toxigenic Microcystis were present in the western and
      eastern basins in the summers of 1999, 2000, and 2002 and the central basin in
      1999 and 2002. This is the most extensive distribution of Microcystis reported in
      Lake Erie. Clone libraries (16S rDNA) of these cyanobacterial communities were
      generated from 7 of the 13 field stations (representing all three basins) to
      partially characterize this microbial community. These libraries were shown to be
      dominated by sequences assigned to the Synechococcus and Cyanobium phylogenetic
      cluster, indicating the importance of picoplankton in this large lake system.

PMID- 16435170
TI  - Application of nonlinear analysis methods for identifying relationships between
      microbial community structure and groundwater geochemistry.
AB  - The relationship between groundwater geochemistry and microbial community
      structure can be complex and difficult to assess. We applied nonlinear and
      generalized linear data analysis methods to relate microbial biomarkers
      (phospholipids fatty acids, PLFA) to groundwater geochemical characteristics at
      the Shiprock uranium mill tailings disposal site that is primarily contaminated
      by uranium, sulfate, and nitrate. First, predictive models were constructed using
      feedforward artificial neural networks (NN) to predict PLFA classes from
      geochemistry. To reduce the danger of overfitting, parsimonious NN architectures
      were selected based on pruning of hidden nodes and elimination of redundant
      predictor (geochemical) variables. The resulting NN models greatly outperformed
      the generalized linear models. Sensitivity analysis indicated that tritium, which
      was indicative of riverine influences, and uranium were important in predicting
      the distributions of the PLFA classes. In contrast, nitrate concentration and
      inorganic carbon were least important, and total ionic strength was of
      intermediate importance. Second, nonlinear principal components (NPC) were
      extracted from the PLFA data using a variant of the feedforward NN. The NPC
      grouped the samples according to similar geochemistry. PLFA indicators of Gram
      negative bacteria and eukaryotes were associated with the groups of wells with
      lower levels of contamination. The more contaminated samples contained microbial
      communities that were predominated by terminally branched saturates and branched
      monounsaturates that are indicative of metal reducers, actinomycetes, and Gram
      positive bacteria. These results indicate that the microbial community at the
      site is coupled to the geochemistry and knowledge of the geochemistry allows
      prediction of the community composition.

PMID- 16435171
TI  - Mechanistic study of the cellular interplay of transport and metabolism using the
      synthetic modeling method.
AB  - PURPOSE: The aims of this study were 1) to demonstrate a new modeling strategy
      that uses experimental computational models built by the synthetic method and 2)
      to study the consequences of spatial alignment, or lack thereof, of P
      glycoprotein (Pgp) and CYP3A4 on the transport and metabolism of drug-like
      compounds and the influence of competitive inhibition by metabolites on the
      transport and metabolism of those compounds. METHODS: The synthetic method of
      modeling and simulation was used to construct discrete-event, discrete-space
      models. Within a framework designed for experimentation, object-oriented software
      components were assembled into devices representing the efflux transport and
      metabolism mechanisms within cell monolayers in Caco-2 transwell systems.
      RESULTS: Conditions for transport and metabolism synergism (and lack thereof)
      were identified. Simulations showed how spatial alignment altered the coordinated
      influences of Pgp and CYP3A4 on absorption of a series of drug-like compounds.
      Within those experiments, when the metabolites were also substrates of Pgp, the
      metabolite levels produced were insufficient to give evidence of a competitive
      inhibitory effect on either transport or metabolism. CONCLUSIONS: The results
      provide evidence of the potential value of using this class of models to improve
      our understanding of how complex cellular processes influence the transport and
      absorption of compounds, and the consequences of interventions.

PMID- 16435172
TI  - False-positive results in neonatal screening for cystic fibrosis based on a three
      stage protocol (IRT/DNA/IRT): Should we adjust IRT cut-off to ethnic origin?
AB  - Since 1979, newborn screening for cystic fibrosis (CF) has been possible by
      measuring immunoreactive tryspinogen (IRT) in blood spots. In France, a programme
      based on a three-stage strategy (IRT/DNA/IRT) started in 2002. In the Rhone-Alpes
      area, the positive screening rate (i.e. the proportion of samples sent for
      genotyping) observed after the first IRT measurement was higher than the expected
      rate (0.65% versus 0.50%), without a greater CF incidence. We hypothesized that
      the IRT reference range could differ according to the ethnic origin of the
      newborns. 35 141 newborns were studied and divided into two groups: European
      ethnic group 26 324 (75%) and North African ethnic group 8817 (25%). 243 positive
      newborns were identified: 146 (60%) in the European ethnic group and 97 (40%) in
      the North African ethnic group. Three CF patients and 11 unaffected heterozygotes
      were found in the European group, but no mutations were found in the North
      African group. Mean IRT values and the percentage of IRT values over the cut-off
      were significantly higher in the North African group than in the European group
      (mean IRT = 21.17 microg/L and 19.74 microg/L, p < 0.0001; %IRT > cut-off = 1.1%
      and 0.5%, respectively). For the positive screened newborns, term and IRT mean
      were comparable, whereas birth weight was higher in the North African ethnic
      group. These results lead us to conclude that (i) newborns from families of North
      African origin have higher IRT values and (ii) most of the positive screened
      newborns in this population could be considered as 'false positives'. These
      conclusions could explain, in part, the large variations seen in the positive
      screening rate in the French CF neonatal screening and raise the question whether
      it is relevant to adapt cut-off to ethnic origin of the newborns.

PMID- 16435173
TI  - The knowledge gap in expanded newborn screening: survey results from
      paediatricians in Massachusetts.
AB  - Massachusetts currently offers an optional expanded newborn screening programme
      that tests for 20 biochemical genetic disorders in addition to the mandated
      newborn screening tests, including phenylketonuria (PKU) and nine other
      biochemical genetic disorders. We conducted a mail survey of 550 paediatricians
      listed in the 2000 Massachusetts Healthcare Directory to determine
      paediatricians' preparedness in discussing expanded newborn screening and its
      results with families, and to determine in what specific format physicians in
      Massachusetts would prefer to receive educational materials and updates. Of
      surveys mailed, 35% (190/550) were returned within the allotted 3 weeks: 25
      paediatricians (14%) were unaware of expanded newborn screening; 78 respondents
      (42%) indicated feeling less than prepared talking about test results with
      families; 100 paediatricians (54%) indicated a lack of information about
      metabolic disorders; 134 (73%) preferred information sent in postal mailings, 62
      (34%) preferred grand rounds, 60 (33%) preferred educational seminars, and 58
      (32%) preferred websites. Other formats receiving preferences of less than 30%
      included e-mail (27%), phone calls (8%), video (6%), and distance learning (1%).
      Paediatricians are ill-prepared for expanded newborn screening for biochemical
      genetic disorders. To address this problem, paediatricians in Massachusetts
      indicated a preference for unsolicited periodic mailings including short reviews
      and brochures.

PMID- 16435174
TI  - Social outcome in treated individuals with inherited metabolic disorders: UK
      study.
AB  - Few data exist on the long-term social outcome of patients with inherited
      metabolic disorders, despite the fact that increasing numbers are surviving into
      adulthood. Here we report the findings of 329 patients aged from 11 to 70 years,
      of whom 172 had phenylketonuria, 38 had homocystinuria and 33 had galactosaemia.
      Twenty-eight per cent had no formal education qualifications, 59% were employed,
      but only 17% were in professional jobs (social classes I and II). The time of
      diagnosis and treatment had a significant impact on outcome in phenylketonuria,
      as did pyridoxine responsiveness or lack of it in homocystinuria. Effects on
      outcome in galactosaemia were not clear. Social integration is an important
      outcome of treatment of chronic disorders in childhood and warrants further study
      in this growing patient population.

PMID- 16435175
TI  - State regulation and response inhibition in children with ADHD and children with
      early- and continuously treated phenylketonuria: an event-related potential
      comparison.
AB  - BACKGROUND: The presentation rate of stimuli plays an important role in
      explaining the performance inefficiency in children with ADHD. In general,
      children with ADHD have been found to perform more poorly in conditions of
      relatively slow event rates as compared with fast and moderate event rates. The
      state regulation hypothesis states that these children have problems in
      correcting their energetic state necessary to counteract a performance decrement,
      which requires extra effort allocation. In this study, we investigated state
      regulation in children with ADHD and used children with early- and continuously
      treated phenylketonuria (PKU) as a clinical contrast group. METHOD: We measured
      the parietal P3 during a Go/No-Go task that incorporated a condition with a fast
      and a slow presentation rate. RESULTS: We were able to show that children with
      ADHD, relative to controls, responded more slowly and more variably in the slow
      condition only, which was accompanied by a smaller P3, suggesting less effort
      allocation. In contrast, the children with PKU did not show a state regulation
      deficit. The PKU group showed prolonged stimulus evaluation processing, as
      indexed by P3 latency, compared to controls and children with ADHD. In addition,
      they made more errors of commission than the controls and the ADHD group.
      CONCLUSIONS: Our electrophysiological data support the state regulation
      hypothesis of ADHD. Only the children with PKU had more problems in inhibiting
      pre-potent responding than controls, which is in accord with the prefrontal
      dysfunction hypothesis of PKU.

PMID- 16435176
TI  - The intake of total protein, natural protein and protein substitute and growth of
      height and head circumference in Dutch infants with phenylketonuria.
AB  - In a previous study, Dutch children with phenylketonuria (PKU) were found to be
      slightly shorter than their healthy counterparts. In the literature, it has been
      hypothesized that a higher protein intake is necessary to optimize growth in PKU
      patients. The study aimed to investigate whether protein intake (total, natural
      and protein substitute) in this group might be an explanatory factor for the
      observed growth. Growth of height and head circumference and dietary data on
      protein intake (total, natural and protein substitute) from 174 Dutch PKU
      patients born between 1974 and 1996 were analysed retrospectively for the
      patients' first 3 years of life. Analyses were corrected for energy intake during
      the first year of life and for the clinical severity of the deficiency of
      phenylalanine hydroxylase by means of plasma phenylalanine concentration at
      birth. Neither protein nor energy intake correlated with height growth. A
      positive, statistically significant relation between head circumference growth
      and natural protein and total protein intake was found, but not with the intake
      of the protein substitute or energy. Therefore, this study suggests that
      improvement of the protein substitute rather than an increase of total protein
      intake may be important in optimizing head circumference growth in PKU patients.

PMID- 16435177
TI  - Predicting the phenylalanine blood concentration from urine analyses. An approach
      to noninvasive monitoring of patients with phenylketonuria.
AB  - The need for regular blood-drawing in the management of chronic metabolic
      disorders may negatively influence the compliance of patients and their parents;
      noninvasive analytical procedures could well alleviate this burden. Using data
      obtained in six adult probands with phenylketonuria, we evaluate the feasibility
      of noninvasive prediction of phenylalanine blood concentrations from analysis of
      phenylalanine and creatinine in urine. Cross-validated regression equations
      correct for the significant inter-individual variation of phenylalanine
      fractional excretion rates. With sensitive and specific enzymatic assays for
      phenylalanine and creatinine, the accuracy of this noninvasive procedure may also
      become clinically satisfactory for the purpose of self-monitoring.

PMID- 16435178
TI  - Platelet serotonin concentrations in PKU patients under dietary control and
      tetrahydrobiopterin treatment.
AB  - Tetrahydrobiopterin (BH4) supplementation has been applied in PKU treatment,
      resulting in successful control of blood phenylalanine (Phe) concentrations. We
      evaluated serotonin status in PKU patients under classical dietary treatment (n =
      40) and in a group of 11 PKU patients under BH4 treatment, both during a 6-month
      period. Platelet serotonin values were significantly lower in PKU patients under
      dietary treatment when compared with controls. A negative correlation was
      observed between plasma Phe and platelet serotonin concentrations (r = -0.367, p
      = 0.017) in PKU patients. Platelet serotonin concentration increased
      significantly after both 1 and 6 months of BH4 therapy when compared with
      baseline conditions (Wilcoxon test: p = 0.013 and p = 0.021, respectively), while
      no differences were observed when comparing plasma Phe concentrations at the
      different points. Our results indicate that PKU patients under classical
      treatment have decreased platelet serotonin concentrations, probably owing to
      continued high Phe values, while BH4 supplementation restored platelet serotonin
      values.

PMID- 16435179
TI  - Renal function in tyrosinaemia type I after liver transplantation: a long-term
      follow-up.
AB  - Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine
      catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results
      in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute
      intermittent porphyria. When treated with liver transplantation, tyrosinaemia
      type I was considered to be cured. Some years after the first liver
      transplantations in these patients, some reports focused on the renal function
      after transplantation. These reports showed that urinary succinylacetone
      excretion remained but that tubular function normalized. In this report we
      discuss the long-term renal follow-up (mean follow-up time 11 years, range 7-14
      years) after liver transplantation in 9 patients with tyrosinaemia type I treated
      by liver transplantation in our centre. An evaluation was made of renal function
      and succinylacetone excretion in urine. In all patients we found a persistent
      excretion of succinylacetone in the urine. With respect to the glomerular
      function, we can conclude that there is no clear change in GFR. At the same time,
      tubulopathy persisted in some patients. We consider that excretion of metabolites
      such as succinylacetone will be an important contributing factor to tubular
      dysfunction after liver transplantation in patients with tyrosinaemia type I.
      Therefore, notwithstanding the major effect of liver transplantation on tyrosine
      metabolism, renal tubular dysfunction remains at risk and needs careful
      monitoring. Progressive tubular dysfunction can cause glomerular damage. The use
      of low-dose NTBC might be considered after liver transplantation in case of
      tubulopathy to prevent progression of tubular and glomerular dysfunction.

PMID- 16435180
TI  - Identification of a common novel mutation in Saudi patients with argininosuccinic
      aciduria.
AB  - We have identified a common novel mutation (Q354X) in the argininosuccinate lyase
      (ASL) gene in Saudi patients with argininosuccinic aciduria (ASAuria; McKusick
      207900). The two index patients were siblings, had a neonatal onset of the
      disease and were diagnosed based on the clinical presentation and confirmed by
      analysis of their dried blood spots (DBS) by tandem mass spectrometry (MS/MS).
      The ASL gene was then analysed by direct sequencing. A further 28 patients with a
      confirmed diagnosis of ASAuria based on MS/MS of their DBS were tested by
      sequencing for the presence of the Q354X mutation. This mutation was found in 14
      out of the 28 patients (50%) tested. Our work indicates that the Q354X allele is
      common, may account for 50% of the abnormal ASL genes in the Saudi population,
      and is likely to be associated with the neonatal form of the disease. We
      recommend that all patients diagnosed with ASAuria in Saudi Arabia or of Arab
      origin be tested for this mutation and for Q116X, which has been described
      previously. In addition, further analysis is needed to identify other underlying
      disease mutations for ASAuria in the Saudi population.

PMID- 16435181
TI  - S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger
      brother of the index patient, and outcomes during therapy.
AB  - S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human
      only once, in a recently described Croatian boy. Here we report the clinical
      course and biochemical abnormalities of the younger brother of this proband. This
      younger brother has the same two mutations in the gene encoding AdoHcy hydrolase,
      and has been monitored since birth. We report, as well, outcomes during therapy
      for both patients. The information obtained suggests that the disease starts in
      utero and is characterized primarily by neuromuscular symptomatology (hypotonia,
      sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination).
      The laboratory abnormalities are markedly increased creatine kinase and elevated
      aminotransferases, as well as specific amino acid aberrations that pinpoint the
      aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy.
      Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although
      the hypermethioninaemia may be absent or nonsignificant in the first weeks of
      life). The disease seems to be at least to some extent treatable, as shown by
      improved myelination and psychomotor development during dietary methionine
      restriction and supplementation with creatine and phosphatidylcholine.

PMID- 16435182
TI  - Asymptomatic adults and older siblings with biotinidase deficiency ascertained by
      family studies of index cases.
AB  - We report 32 biotinidase-deficient patients detected by family studies in the
      index cases. The study group consisted of 10 mothers, 4 fathers and 18 siblings.
      There were 17 individuals (3 mothers, 4 fathers and 10 siblings) with profound
      biotinidase deficiency (BD) (< 10% of mean normal activity) and 15 (7 mothers and
      8 siblings) with partial BD (10-30% of mean normal activity). In the profound BD
      group, only three siblings were symptomatic. Dermatitis, microcephaly,
      developmental delay and convulsions were observed. The patients with partial BD
      did not have any clinical symptoms except one sibling with borderline IQ score.
      None of the parents was symptomatic. Family investigation of patients with BD is
      very important for the detection of asymptomatic patients who are at risk of
      exhibiting symptoms at any age. Careful evaluation of these untreated individuals
      with BD is important to obtain additional information about the natural history
      of this disorder and may provide clues to phenotype-genotype relationships and
      treatment regimes.

PMID- 16435183
TI  - Determination of the GABA analogue succinic semialdehyde in urine and
      cerebrospinal fluid by dinitrophenylhydrazine derivatization and liquid
      chromatography-tandem mass spectrometry: application to SSADH deficiency.
AB  - Succinic semialdehyde (SSA) accumulates in the inborn error of meta- bolism
      succinic semialdehyde dehydrogenase deficiency owing to impaired enzymatic
      conversion to succinic acid. We developed a stable-isotope dilution liquid
      chromato- graphy-tandem mass spectrometry method for the determination of SSA in
      urine and cerebrospinal fluid samples. Stable-isotope-labelled [13C4]SSA, serving
      as internal standard, was prepared by reaction of ninhydrin with L-[13C5]glutamic
      acid. SSA in body fluids was converted to its dinitrophenylhydrazine (DNPH)
      derivative, without sample purification prior to the derivatization procedure.
      The DNPH derivative of SSA was injected onto a C18 analytical column and
      chromatography was performed by isocratic elution. Detection was accomplished by
      tandem mass spectrometry operating in the negative multiple-reaction monitoring
      mode. The limit of detection was 10 nmol/L and the calibration curves over the
      range 0-500 pmol of SSA showed good linearity (r2 > 0.99). The intra-day
      coefficient of variation (n = 10) for urine was 2.7% and inter-day coefficient of
      variation (n = 5) for urine was 8.5%. The average recoveries performed on two
      levels by enriching urine and cerebrospinal fluid samples ranged between 85 and
      115%, with coefficients of variation < 8%. The method enabled the first
      determination of normal values for SSA in urine and pathological values of SSA in
      urine and cerebrospinal fluid samples derived from patients with succinic
      semialdehyde dehydrogenase deficiency.

PMID- 16435184
TI  - Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance
      to D-2-hydroxyglutaric and gamma-hydroxybutyric acidurias.
AB  - We investigated the presence of hydroxyacid-oxoacid transhydrogenase (HOT), which
      catalyses the cofactor-independent conversion of gamma-hydroxybutyrate (GHB) to
      succinic semialdehyde coupled to reduction of 2-ketoglutarate (2-KG) to D-2
      hydroxyglutarate (D-2-HG), in human liver extracts employing [2H6]GHB and 2-KG as
      substrates. We measured incorporation of 2H in D-[2H]2-HG using GC-MS analyses,
      providing evidence for HOT activity in humans. Kinetic characterization of HOT
      was undertaken in forward and reverse directions. We employed [2H6]GHB and [2H4]2
      KG as cosubstrates in order to develop a HOT activity assay in cultured human
      fibroblasts derived from patients with D-2-hydroxyglutaric aciduria. HOT activity
      was quantified in this system by the measurement of D-[2H5]2-HG production.
      Fibroblasts derived from patients with D-2-hydroxyglutaric aciduria showed normal
      HOT activities. Our results provide the first demonstration and preliminary
      kinetic characterization of HOT activity in human tissues.

PMID- 16435185
TI  - Body composition in children with galactosaemia.
AB  - Body composition in classical galactosaemia has not been studied. Patients with
      classical galactosaemia, an inherited disorder of galactose metabolism caused by
      deficiency of galactose-1-phosphate uridyltransferase (GALT, EC 2.7.7.10), might
      be at risk for an abnormal body composition because of intrinsic factors related
      to galactosaemia and/or diet-related factors. The aim of this study was to
      evaluate the body composition of children with classical galactosaemia. The
      studied population was a previously reported group of classical galactosaemia
      patients (13 male and 27 female, ages 3-17 years) with decreased height, weight,
      weight-for-height and insulin-like growth factor-I (IGF-I) Z-scores. Body
      composition data were obtained by dual-energy X-ray absorptiometry (DXA). In
      order to correct for height, fat mass (FM) and lean tissue mass (LTM) were
      divided by squared height. Mid-parental target height Z-scores were assessed and
      compared to actual height Z-scores. Linear and multiple regression analysis were
      done to investigate the relationship between body composition and IGF-I, dietary
      intake and growth data. We found decreased height Z-scores when compared to mid
      parental target height Z-scores. Mean scores for FM and LTM (both adjusted for
      height) were decreased. LTM (adjusted for height) and height Z-score were
      correlated with IGF-I Z-score. FM (adjusted for height) was correlated with soy
      intake. No correlation was found between soy intake and IGF-I Z-score. In this
      limited group of patients, height is decreased and body composition is abnormal.
      The decreased levels of IGF-I and/or soy nutrition might play a role in these
      findings.

PMID- 16435186
TI  - Mutation spectrum of type I glycogen storage disease in Hungary.
AB  - We performed mutation analysis in 12 Hungarian type I glycogen storage disease
      (GSD I) patients in order to determine the mutation spectrum. All patients were
      clinically classified as GSD Ia. Nine patients carried biallelic G6PC mutations
      (p.Q27fsX35, p.D38V, p.W70X, p.K76N, p.W77R, p.R83C, p.E110Q, p.G222R), with
      E110Q reported only in Hungary. However, three patients displayed two common
      G6PT1 (SLC37A4) mutations (p.L348fsX400, p.C183R) which were originally described
      in association with GSD Inon-a. Review of the literature and our data show that
      G6PT1 mutations are not associated with neutropenia and related clinical findings
      in approximately 10% of these cases. Homozygosity for the truncating G6PT1
      mutation p.L348fsX400 can be observed with and without neutropenia, indicating
      that one or more modifiers of the action of G6PT1 exist. Our data are suitable to
      provide DNA-based and thus noninvasive confirmation of diagnosis in Hungarian
      patients with this disorder.

PMID- 16435187
TI  - Decreased plasma concentration of von Willebrand factor antigen (VWF:Ag) in
      patients with glycogen storage disease type Ia.
AB  - Despite highly increased blood lipids, patients with glycogen storage disease
      type Ia (GSD Ia) do not develop premature vascular complications. Since this
      could be due to changes of coagulation factors, coagulation tests (including von
      Willebrand factor (VWF) antigen (VWF:Ag) ELISA, VWF:collagen binding activity
      (VWF:CB) and VWF multimer analysis) were performed in 10 GSD Ia patients, single
      cases of other GSD types, and in both healthy and hyperlipidaemic controls. In
      60% of GSD Ia patients we found abnormal results, with a decrease of VWF:Ag and
      multimer analysis showing reduced intensity of individual oligomers in the
      presence of all multimers with a normal triplet structure. We interpret these
      findings as an acquired 'von Willebrand syndrome type I' in GSD Ia. The
      underlying metabolic mechanism and a potential role in the protection from
      vascular complication still needs to be evaluated.

PMID- 16435188
TI  - Analysis of polyols in urine by liquid chromatography-tandem mass spectrometry: a
      useful tool for recognition of inborn errors affecting polyol metabolism.
AB  - Several inborn errors of metabolism with abnormal polyol concentrations in body
      fluids are known to date. Most of these defects can be diagnosed by the
      assessment of urinary concentrations of polyols. We present two methods using
      tandem mass spectrometry for screening for inborn errors affecting polyol
      metabolism. Urine samples supplemented with internal standards ([13C4]erythritol,
      [13C2]arabitol and [2H3]sorbitol) were desalted by a mixed-bed ion-exchange
      resin. Separation was achieved by two different columns. Sugar isomers could not
      be separated using a Prevail Carbohydrate ES 54 column (method 1), whereas with
      the other column (Aminex HPX-87C) separation of the isomers was achieved (method
      2). Multiple reaction monitoring polyol detection was achieved by tandem mass
      spectrometry with an electron ion-spray source operating in the negative mode.
      Age-related reference ranges of polyols (erythritol, treitol, arabitol, ribitol,
      xylitol, galactitol, mannitol, sorbitol, sedoheptitol and perseitol) in urine
      were established. The applicability of the method was demonstrated by the
      abnormal polyol concentrations observed in patients with transaldolase
      deficiency, ribose-5-phosphate isomerase deficiency and classical galactosaemia.
      This paper describes two methods for the analysis of urinary polyols by liquid
      chromatography-tandem mass spectrometry. Method 1 is a fast screening method with
      the quantification of total isomers and method 2 is a more selective method with
      the separate quantification of the polyols. Both methods can be used for
      diagnosing inborn errors of metabolism affecting polyol metabolism.

PMID- 16435189
TI  - A novel assay for the prenatal diagnosis of Sjogren-Larsson syndrome.
AB  - Sjogren-Larsson syndrome (SLS) is a metabolic disorder characterized by
      ichthyosis, mental retardation and spastic diplegia or tetraplegia. The
      biochemical defect has been identified as a deficiency of fatty aldehyde
      dehydrogenase (FALDH), which is part of an enzyme complex that converts fatty
      alcohols into fatty acids. Making use of the finding that FALDH is also involved
      in the degradation of phytol, we set up an enzymatic assay for the prenatal
      diagnosis of SLS in cultured chorionic villus fibroblasts (CVF) based on a
      deficiency in the conversion of phytol to phytenic acid. FALDH activity was
      assessed by incubating fibroblast homogenates with phytol in the presence of
      NAD+, followed by hexane extraction of the samples and quantification of phytenic
      acid production by gas chromatography-mass spectrometry (GC-MS). FALDH activity
      could be detected in cultured CVF cells derived from control fetuses and the
      activity was found to be markedly deficient in cultured CVF cells derived from an
      affected SLS fetus. The new assay described in this paper has advantages over
      previous assays and we conclude that it may well contribute to the prenatal
      detection of SLS.

PMID- 16435190
TI  - Effect of copper and diethyldithiocarbamate combination therapy on the macular
      mouse, an animal model of Menkes disease.
AB  - Menkes disease (MD) is a neurodegenerative disorder characterized by a copper
      deficiency in the brain. It is caused by the defective intestinal absorption of
      copper resulting from a deficiency of a copper-transporting ATPase, ATP7A. This
      gives rise to an accumulation of copper in the intestine. The copper deficiency
      in the brain of MD patients cannot be improved by copper injections, because the
      administered copper accumulates at the blood-brain barrier and is not transported
      across to the neurons. To resolve this problem, we investigated the effect of a
      combination therapy of copper and sodium diethyldithiocarbamate (DEDTC), a
      lypophilic chelator, in an animal model of MD, the macular mouse. Four-week-old
      macular mice treated with 50 mug of CuCl2 on the 7th day after birth were used.
      Experimental mice were given a subcutaneous injection of CuCl2 (4 microg) and an
      intraperitoneal injection of DEDTC (0.2 mg/g body weight) twice a week for 4
      weeks and then sacrificed. Copper concentrations and cytochrome-c oxidase
      activity in the brains of treated mice were higher than those of control macular
      mice, which received only copper or saline. The ratios of brain noradrenaline to
      dopamine and of adrenaline to dopamine were also increased by the treatment,
      suggesting that the activity of dopamine beta-hydroxylase, a copper-dependent
      enzyme, was improved by the treatment. Liver and renal function tests showed no
      abnormalities in the treated mice, although copper concentrations in the kidneys
      of treated mice were higher than those of control macular mice. These results
      suggest that DEDTC facilitates the passage of copper across the blood-brain
      barrier and that the combination therapy of copper and DEDTC may be an effective
      treatment for the neurological disturbances suffered by patients with MD.

PMID- 16435191
TI  - External quality assurance programme for enzymatic analysis of lysosomal storage
      diseases: a pilot study.
AB  - Inborn errors of metabolism are rare and laboratories performing diagnostic tests
      in this field must participate in external quality assurance (EQA) schemes to
      demonstrate their competence and also to maintain sufficient experience with
      patient material. EQA schemes for metabolite analyses are available (ERNDIM), but
      corresponding EQA schemes for enzyme analyses are nonexistent. In this paper we
      describe a pilot study on lysosomal enzyme testing by four centres in The
      Netherlands. Quantitative aspects of EQA were studied by interlaboratory
      comparison of activities of six lysosomal enzymes in a series of buffy coat
      samples. Interlaboratory variance was enormous. To reduce variance caused by
      methodological differences, participants reported enzyme activities relative to
      mean normal values. Beta-D-Galactosidase activities compared well between the
      participating laboratories (average interlaboratory CV 13%), but for other
      enzymes large differences were observed, e.g. sphingomyelinase (average CV 38%).
      Diagnostic proficiency was tested with cultured fibroblasts. In 45 out of a total
      of 48 tests (12 cell lines, 4 participants) the correct diagnosis was
      accomplished on the basis of merely biochemical investigations, i.e. without
      clinical data of the patients. In a survey using blood of a late-onset Pompe
      disease patient, less conclusive results were obtained. A stable enzyme source
      was developed for easy distribution. Most lysosomal enzymes were stable upon
      lyophilization of leukocyte homogenates and during subsequent storage of the
      freeze-dried material at room temperature, in particular when cryolyoprotectant
      was added. Shipment of such lyophilized samples is simple and cheap and ideal for
      an EQA scheme. Our study shows that an EQA programme for enzymatic testing of
      lysosomal storage diseases is necessary to accomplish reliable diagnostic
      procedures for lysosomal storage diseases. We recommend that EQA for lysosomal
      enzymes be implemented through ERNDIM.

PMID- 16435192
TI  - A comparative study of cytoplasmic granules imaged by the real-time microscope,
      Nile Red and Filipin in fibroblasts from patients with lipid storage diseases.
AB  - Cytoplasmic granules in fibroblasts, visualized without stains, or labelled with
      Nile red, Filipin, or anti-LAMP-1 (lysosome-associated membrane protein 1), were
      imaged using the real-time microscope (RTM). New advances in light microscope
      technology were applied to detect cytoplasmic granules (RTM-visible granules) and
      characterize them by imaging contrast, size, shape, cellular distribution,
      composition, motion dynamics and quantity. Appearing as solid spheroids or ring
      structures, the majority of the RTM-visible granules contained Nile-red labelled
      neutral lipids. A smaller subpopulation, appearing dimmer, with less imaging
      contrast, contained Filipin-labelled free cholesterol. Most lipid storage
      granules have a diameter ranging from 0.3 mum to 0.6 mum, with a small population
      measuring up to 1 mum. They typically clustered in the perinuclear region and
      displayed relatively small oscillatory motion. Immunofluorescence based on LAMP-1
      labelling highlighted granular structures that were distinct and separate from
      RTM-visible granules and other structures in the light modality of the
      microscope. RTM-visible granules were associated with disease phenotypes that
      have increased cellular neutral lipid stores corresponding to the Nile red
      labelled droplets (e.g. triacylglycerides, cholesterol esters). As predicted, the
      fibroblast strains with a defect resulting in Wolman disease, when compared to
      control samples, consistently had RTM-visible granules, higher in imaging
      contrast and with larger diameters, that were labelled with Nile red, and also an
      increased frequency of Filipin-cholesterol complexes. By comparison, in
      fibroblasts where the lipid storage is less evident (Gaucher and Farber diseases)
      or from GM(1) gangliosidosis, where the primary storage substances are
      oligosaccharides, fewer and smaller RTM-visible granules were observed. In some
      cases, changes in contrast and morphology in the unstained cytoplasmic
      compartments were more evident than in the labelled structures. In summary,
      applying the RTM imaging system to fibroblasts enables differences between the
      various disease types to be seen and, in specific examples, a unique phenotype
      can be readily discerned.

PMID- 16435193
TI  - Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood
      galactocerebrosidase activity and polymorphic mutations.
AB  - Globoid cell leukodystrophy is an inherited metabolic disorder of the central
      nervous system caused by deficiency of the lysosomal enzyme galactocerebrosidase.
      Haematopoietic stem cell transplantation is the only available effective
      treatment. The engraftment from normal donors provides competent cells able to
      correct the metabolic defect. Umbilical cord blood cells have proved to
      significantly decrease complications and improve engraftment rate compared to
      adult marrow cells in haematopoietic stem cell transplantation. Umbilical cord
      blood cells must be of sufficient activity to provide central nervous system
      recovery after engraftment is obtained. Galactocerebrosidase activity is known to
      be affected by two polymorphic alleles found at nucleotides 502 and 1637 of the
      cDNA for this gene. This enzyme activity and the polymorphic alleles noted above
      were analysed in 83 random samples of umbilical cord blood. The activity, assayed
      with the fluorogenic substrate 6-hexadecanoylamino-4-methylumbelliferyl-beta
      galactopyranoside, in those with neither polymorphic allele was 4.6 +/- 1.7 units
      (nmol/h per mg protein). This optimal choice of cord blood was found in only 24%
      of specimens. Homozygotes for 1637T > C with activity of only 1.5 +/- 0.4 units
      represented 16% of the samples. Those heterozygous for 1637T > C with slightly
      better activity (2.3 +/- 0.7 units) represented 52% of the samples. Choice of
      umbilical cord blood for haematopoietic stem cell transplantation, therefore,
      requires consideration not only of cell quantity and HLA compatibility but also
      selection for normal alleles to obtain maximal enzymatic activity for central
      nervous system correction.

PMID- 16435194
TI  - Cumulative incidence rates of the mucopolysaccharidoses in Germany.
AB  - In order to estimate the cumulative incidence rates of the mucopolysaccharidoses
      (MPS) in Germany, a retrospective epidemiological survey covering the period
      between 1980 and 1995 was implemented. Multiple ascertainment sources were used
      to identify affected patients. A prevalence of approximately 0.69 cases per
      100,000 births was obtained for MPS I (Hurler phenotype). Within the study
      period, 4 patients with Hurler/Scheie phenotype and 7 cases with Scheie disease
      were detected. The cumulative incidence for MPS II (Hunter syndrome) was
      estimated as 0.64 cases per 100,000 births (1.3 cases per 100,000 male live
      births); that for MPS III (Sanfilippo syndrome types A, B and C) as 1.57 cases in
      100,000 births; that for MPS IV A (Morquio syndrome) as 0.38 cases in 100,000;
      and that for MPS VI (Maroteaux-Lamy syndrome) as 0.23 cases per 100,000 births.
      Two cases of MPS IVB (beta-galactosidase deficiency) have been identified, but no
      patients with MPS VII or MPS IX. A relatively high number of patients with MPS
      IIIB, MPS IVA and MPS VI were of Turkish origin. The crude rate for all types of
      mucopolysaccharidoses is approximately 3.53 cases in 100,000 live births. The
      cumulative incidence pattern of MPS in Germany was compared with the
      corresponding rates among other industrial nations obtained from recent
      literature: the crude cumulative rates for all types of mucopolysaccharidoses
      (3.4-4.5 in 100,000 live births) were similar among all published populations;
      however, different frequencies of the various forms of MPS were observed.

PMID- 16435195
TI  - Mucopolysaccharidosis I: Alpha-L-Iduronidase mutations in three Tunisian
      families.
AB  - Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease resulting
      from the defective activity of the enzyme alpha-L-iduronidase (IDUA). The disease
      has severe and milder phenotypic subtypes. The IDUA mutations in five MPS I
      patients from three unrelated families from central and southern Tunisia were
      determined by amplifying and sequencing each of the IDUA exons and intron-exon
      junctions. Two novel IDUA mutations, c.1805delTinsGAACA in exon 13 and I270S in
      exon 7, and two previously reported mutations, P533R and R628X, were detected.
      The two patients in family 1 who had the Hurler phenotype were homoallelic for
      the novel deletion-insertion mutation. The patient in family 2 who also had the
      Hurler phenotype was heteroallelic for the novel missense mutation I270S and the
      previously reported nonsense mutation R628X. The two patients in family 3 who had
      the Hurler-Scheie phenotype were homoallelic for P533R. In addition, six known
      IDUA polymorphisms were identified. These are the first Tunisian MPS I patients
      to be genotyped. The identification of these mutations and their genotype
      phenotype correlations should facilitate prenatal diagnosis and counselling for
      MPS I in Tunisia, where a very high rate of consanguinity exists.

PMID- 16435196
TI  - Mucopolysaccharidosis type VI: Identification of novel mutations on the
      arylsulphatase B gene in South American patients.
AB  - Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome, MPS VI) is an autosomal
      recessive disorder caused by deficiency of N-acetylgalactosamine-4-sulphatase
      (ARSB),which leads to the lysosomal accumulation and excretion of dermatan
      sulphate (DS). In this study, 13 unrelated MPS VI patients (12 Brazilian and 1
      Chilean) were investigated regarding the identification of the ARSB gene
      mutations using PCR, SSCP and sequencing. The exons with altered mobility on SSCP
      were sequenced, as well as all the exons of patients with no SSCP alteration.
      Seven novel mutations were identified: D59N, L72R, Q88H, P93S, R197X, 1279delA
      and c.1143-8T > G. The previously reported mutations 1533del23, R315Q and 427delG
      were found in six, three and two alleles respectively. The other mutations
      already reported, S384N and G144R, were found in only one allele. In addition,
      three polymorphisms previously described (V358M, V376M and P397P) were detected
      in the patients analysed. Our findings are in agreement with the literature
      confirming the great genetic heterogeneity associated with MPS VI.

PMID- 16435197
TI  - Nonviral in vivo gene transfer in the mucopolysaccharidosis I murine model.
AB  - Mucopolysaccharidosis I (MPS I) is a lysosomal disorder characterized by a
      deficiency of the enzyme alpha-L: -iduronidase (IDUA), which is responsible for
      the degradation of glycosaminoglycans (GAGs). This deficiency leads to the
      accumulation of dermatan and heparan sulphate in lysosomes. Presently available
      treatments include bone marrow transplantation and enzyme replacement therapies,
      both of which are limited in their effects. In this work, knockout (KO) MPS I
      mice were treated with a nonviral vector containing the human IDUA cDNA. KO mice
      were transfected by hydrodynamic injection of pRIDUA in the caudal vein (i.v., n
      = 3) or by intraperitoneal injection of pRIDUA/Superfect complexes (i.p., n = 3).
      GAG concentration and IDUA activity were analysed in the kidneys, spleen, lungs,
      brain and liver. The expression of IDUA in the organs of i.v.- and i.p.-treated
      mice was also analysed by real-time reverse-transcription (RT) PCR and compared
      by relative quantification. The concentration of GAGs in the organs differed
      between KO and wild-type mice. In the spleen and liver, GAG levels were lower in
      i.v.- and i.p.-treated KO mice than in control nontreated animals. Real-time RT
      PCR showed that the transgene is expressed in all the analysed organs of i.p.-
      and i.v.-treated KO mice. Enzyme activity was similarly observed in all the
      organs analysed. Our data suggest that this kind of transfection may be a useful
      tool for studies of nonviral protocols for gene therapy of MPS.

PMID- 16435198
TI  - Marrow stromal cells from patients affected by MPS I differentially support
      haematopoietic progenitor cell development.
AB  - Bone marrow transplantation is the therapy of choice in patients affected by MPS
      I (Hurler syndrome), but a high incidence of rejection limits the success of this
      treatment. The deficiency of alpha-L-iduronidase (EC 1.2.3.76), one of the
      enzymes responsible for the degradation of glycosaminoglycans, results in
      accumulation of heparan and dermatan sulphate in these patients. Heparan sulphate
      and dermatan sulphate are known to be important components of the bone marrow
      microenvironment and critical for haematopoietic cell development. In this study
      we compared the ability of marrow stromal cells from MPS I patients and healthy
      donors to support normal haematopoiesis in Dexter-type long term culture. We
      found an inverse stroma/supernatant ratio in the number of clonogenic
      progenitors, particularly the colony-forming unit granulocyte-machrophage in MPS
      I cultures when compared to normal controls. No alteration in the adhesion of
      haematopoietic cells to the stroma of MPS I patients was found, suggesting that
      the altered distribution in the number of clonogenic progenitors is probably the
      result of an accelerated process of differentiation and maturation. The use of
      alpha-L-iduronidase gene-corrected marrow stromal cells re-established normal
      haematopoiesis in culture, suggesting that correction of the bone marrow
      microenvironment with competent enzyme prior to transplantation might help
      establishment of donor haematopoiesis.

PMID- 16435199
TI  - Dietary rescue of fumble--a Drosophila model for pantothenate-kinase-associated
      neurodegeneration.
AB  - Hallervorden-Spatz syndrome (HSS) is a devastating neurological disease,
      characterized by iron accumulation in the globus pallidus in the basal ganglia.
      Most HSS cases are caused by mutations in one of the four human pantothenate
      kinases (PANK2). This PANK2-caused subgroup of HSS is sometimes referred as PKAN
      (pantothenate-kinase-associated neurodegeneration). No effective treatment for
      PKAN or HSS is currently available. fumble, a Drosophila mutant that carries a
      mutation in Drosophila Pank, has many features similar to those of PKAN patients.
      In this study, we used fumble as a model to evaluate various compounds or
      nutritional products for their possible therapeutic efficacy. While no product
      was found to dramatically improve the symptoms, GKE (containing Ginkgo biloba
      extract and flavone) and vitamin E showed statistically significant beneficial
      effects. Our studies indicate that pantothenate is of limited value in
      alleviating fumble phenotypes and also suggest that some compounds might have
      deleterious effects.

PMID- 16435200
TI  - Deletion of the Caenorhabditis elegans homologues of the CLN3 gene, involved in
      human juvenile neuronal ceroid lipofuscinosis, causes a mild progeric phenotype.
AB  - The CLN3 gene is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or
      Batten-Spielmeyer-Vogt disease, a severe hereditary neurodegenerative lysosomal
      storage disorder characterized by progressive disease pathology, with loss of
      vision as the first symptom. Another characteristic of JNCL is the lysosomal
      accumulation of autofluorescent lipopigments, forming fingerprint storage
      patterns visible by electron microscopy. The function of the CLN3 protein is
      still unknown, although the evolutionarily conserved CLN3 protein is being
      functionally analysed using different experimental models. We have explored the
      potential of the nematode Caenorhabditis elegans as a model for Batten disease in
      order to bridge the gap between the unicellular yeast and very complex mouse JNCL
      models. C. elegans has three genes homologous to CLN3, for each of which deletion
      mutants were isolated. Cln-3.1 deletion mutants have a decreased lifespan, and
      cln-3.2 deletion mutants a decreased brood size. However, the neuronal or
      movement defects and aberrant lipopigment distribution or accumulation observed
      in JNCL were not found in the worms. To detect possible redundancy, single
      deletion mutants were crossed to obtain double and triple mutants, which were
      viable but showed no JNCL-specific defects. The cln-3 triple mutants show a more
      prominent decrease in lifespan and brood size, the latter most conspicuously at
      the end of the egg-laying period, suggesting premature ageing. To focus our
      functional analysis we examined the C. elegans cln-3 expression patterns, using
      promoter-GFP (green fluorescent protein) gene fusions. Fluorescence patterns
      suggest cln-3.1 expression in the intestine, cln-3.2 expression in the hypoderm,
      and cln-3.3 expression in intestinal muscle, male-specific posterior muscle and
      hypoderm. Further life stage- and tissue-specific analysis of the processes
      causing the phenotype of the cln-3 triple mutants may provide more information
      about the function of the cln-3 protein and contribute to a better understanding
      of the basic processes affected in Batten disease patients.

PMID- 16435201
TI  - Pulmonary hypertension--a new manifestation of mitochondrial disease.
AB  - Mitochondrial respiratory chain (RC) abnormalities in children can present as
      multiorgan disease, including liver failure, usually within the first year of
      life. Cardiorespiratory complications have previously been described in
      association with RC defects; however, to our knowledge no cases of pulmonary
      hypertension have been described. We discuss two patients with proven
      mitochondrial RC liver disease who developed severe pulmonary hypertension, one
      subsequent to cadaveric orthotopic liver transplantation, the second in the
      neonatal period. It is our contention that pulmonary hypertension should now be
      included as another potential manifestation of paediatric mitochondrial disease.

PMID- 16435202
TI  - Mutation detection in four candidate genes (OXA1L, MRS2L, YME1L and MIPEP) for
      combined deficiencies in the oxidative phosphorylation system.
AB  - Mitochondria are the main energy-producing organelles of the cell. Five complexes
      embedded in the mitochondrial inner membrane, together constituting the oxidative
      phosphorylation (OXPHOS) system, comprise the final steps in cellular energy
      production. Many patients with a mitochondrial defect suffer from a so-called
      combined deficiency, meaning that the enzymatic activities of two or more
      complexes of the OXPHOS system are decreased. Numerous mutations have been
      described in nuclear genes that are involved in the functioning of a single
      complex of the OXPHOS system. However, little attention has been paid to patients
      with a deficiency of more than one complex of this particular system. In this
      study we have investigated four nuclear genes (OXA1L, MRS2L, YME1L and MIPEP)
      that might be involved in the pathology of combined enzymatic deficiencies of the
      OXPHOS system. Based on the results of yeast knockouts of these four proteins, we
      have sequenced the open reading frame of OXA1L in eight patients with an
      enzymatic deficiency of complexes I and IV. MRS2L, YME1L and MIPEP have been
      sequenced in three patients with a combined defect of complexes III and IV. No
      mutations were detected in these patients, showing that at least in these
      patients the OXPHOS system deficiency cannot be explained by a mutation in these
      four genes.

PMID- 16435203
TI  - Anxiety and depression in the acute porphyrias.
AB  - A previous study of self-rated psychosocial aspects in patients with acute
      porphyria found that depression, and particularly anxiety, is more common in
      porphyria patients than in the general population or general medical outpatient
      attenders. Nearly half of the sample (46%) reported at least some problem with
      anxiety and/or depression: anxiety caseness was 26% and depression caseness was
      13%. This paper extends our previous observations and investigates further the
      associations between porphyria and anxiety, depression and general mental health
      in 90 patients (58 acute intermittent porphyria, 32 variegate porphyria). The
      findings of this study confirm that anxiety is raised in patients with acute
      intermittent porphyria and with variegate porphyria, in both males and females,
      compared to the normative population and, using a series of questionnaires
      exploring the physical and psychosocial features of anxiety, that this anxiety is
      experienced as a 'relatively stable personality trait', rather than a 'transitory
      emotional state' (i.e. intrinsic rather than secondary to the porphyria).

PMID- 16435204
TI  - Comprehensive analysis of pyrimidine metabolism in 450 children with unspecific
      neurological symptoms using high-pressure liquid chromatography-electrospray
      ionization tandem mass spectrometry.
AB  - To evaluate the significance of inborn metabolic disorders of the pyrimidine
      degradation pathway, 450 children with unspecific neurological symptoms were
      comprehensively studied; 200 healthy children were recruited as controls. Uracil
      and thymine as well as their degradation products in urine were determined with
      an improved method based on reversed-phase HPLC coupled with electrospray
      ionization tandem mass spectrometry and detection by multiple-reaction monitoring
      using stable-isotope-labelled reference compounds as internal standards. From the
      results of the control group we established age-related reference ranges of all
      pyrimidine degradation products. In the patient group, two children with
      dihydropyrimidine dehydrogenase (DPYD) deficiency were identified; one of these
      was homozygous for the exon 14-skipping mutation of the DPYD gene. In addition,
      two patients with high uracil, dihydrouracil and beta-ureidopropionate were found
      to have ornithine transcarbamylase deficiency. In the urine of 9 patients, beta
      alanine was markedly elevated owing to treatment with vigabatrin, an irreversible
      inhibitor of GABA transaminase, which interferes with beta-alanine breakdown.
      Four patients had exclusively high levels of beta-aminoisobutyrate (beta-AIB) due
      to a low activity of the D-beta-AIB-pyruvate aminotransferase, probably without
      clinical significance. In conclusion, quantitative investigation of pyrimidine
      metabolites in children with unexplained neurological symptoms, particularly
      epileptic seizures with or without psychomotor retardation, can be recommended as
      a helpful tool for diagnosis in clinical practice. Sensitive methods and age
      related reference ranges enable the detection of partial enzyme deficiencies.

PMID- 16435205
TI  - Phenotypic heterogeneity in biochemical parameters correlates with mutations in
      AGPAT2 or Seipin genes among Berardinelli-Seip congenital lipodystrophy patients.
AB  - The Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is characterized
      by a near-total congenital absence of fat and predisposition to develop diabetes
      mellitus. We have previously reported that 22 patients from 16 consanguineous
      pedigrees living in the northeastern region of Brazil had a homozygous 669insA
      mutation in the Seipin gene (BSCL2 locus), while all of the 10 investigated
      subjects from the southeastern region were homozygous for a 1036 bp deletion in
      the AGPAT2 gene (BSCL1 locus). In this study, we compared the serum insulin and
      insulin resistance (HOMA), leptin, triglyceride and fasting glucose levels in
      individuals of these two genetically distinct clusters of BSCL subjects. The
      onset of diabetes was also estimated. The fasting glucose and triglyceride levels
      were not significantly different in these groups. Significant differences were
      detected for leptin, insulin and insulin resistance. BSCL1 patients presented
      lower serum leptin levels compared to BSCL2 patients. BSCL2 subjects had earlier
      onset of diabetes and higher insulin levels. In agreement, BSCL2 patients were
      more insulin resistant, as detected by HOMA. These results indicate phenotypic
      heterogeneity between BSCL1 and BSCL2 Brazilian subjects.

PMID- 16435206
TI  - Hyperammonaemic encephalopathy induced by a commercial very-low-energy diet in a
      neglected ornithine-carbamoyltransferase-deficient woman.
AB  - This case report describes a 31-year-old woman with a neglected ornithine
      carbamoyltransferase deficiency, admitted for a hyperammonaemic encephalopathy
      induced by a commercial very low-energy diet. To our knowledge, this is the first
      reported case and it underlines the potential risk of such a diet in patients
      with undiagnosed or neglected ornithine carbamoyltransferase deficiency.

PMID- 16435207
TI  - Severe hypoglycaemia in isolated 3-methylcrotonyl-CoA carboxylase deficiency; a
      rare, severe clinical presentation.
AB  - Since the introduction of neonatal screening for branched-chain organic
      acidurias, it has been noted that isolated 3-methylcrotonyl-CoA carboxylase
      deficiency is probably one of the most frequent organic acidurias. Only a few
      cases with severe clinical presentation have been described. Profound
      hypoglycaemia is an uncommon but life-threatening complication.

PMID- 16435208
TI  - Methylcrotonyl-CoA carboxylase (MCC) deficiency associated with severe muscle
      pain and physical disability in an adult.
AB  - We present a patient with methylcrotonyl-CoA carboxylase (MCC) deficiency
      (McKusick 210200) who suffered from severe muscle pain and physical disability,
      and propose that this disorder be considered in the differential diagnosis of
      adult patients presenting with muscle pain and weakness.

PMID- 16435209
TI  - First-trimester enzymatic and molecular prenatal diagnosis of mevalonic aciduria.
AB  - Prenatal diagnosis was offered to a family at risk of mevalonic aciduria. A
      chorionic villus sample was obtained and both mevalonate kinase activity and
      mutation analysis were done. An affected fetus was diagnosed.

PMID- 16435210
TI  - Retinitis pigmentosa in mevalonate kinase deficiency.
AB  - Retinitis pigmentosa can occur as a complication of mevalonate kinase deficiency.
      This may be due to the unique isoprenoid metabolism in the retina. Early
      detection requires awareness on the part of the treating physician.

PMID- 16435211
TI  - Mucopolysaccharidosis I under enzyme replacement therapy with laronidase--a
      mortality case with autopsy report.
AB  - There is little information about MPS I-related complications during laronidase
      therapy. We describe the first autopsy report of a young male MPS I patient who
      died of infection-induced cardiopulmonary failure following 2 years of weekly
      treatment with laronidase.

PMID- 16435212
TI  - Clinical, biochemical, magnetic resonance imaging (MRI) and proton magnetic
      resonance spectroscopy (1H MRS) findings in a fourth case of combined D- and L-2
      hydroxyglutaric aciduria.
AB  - We report the fourth case of combined D-and L-2-hydroxyglutaric aciduria
      presenting with neonatal encephalopathy and subependymal cysts.

PMID- 16435213
TI  - Rhabdomyolysis in early-onset very long-chain acyl-CoA dehydrogenase deficiency
      despite normal glucose after fasting.
AB  - A patient with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency
      presented in the neonatal period with hypoketotic hypoglycaemia and at the age of
      1 year with rhabdomyolysis and normal glucose after fasting. Rhabdomyolysis may
      occur in the absence of hypoglycaemia in young infants as well as in older
      patients.

PMID- 16435214
TI  - Trial of erythropoietin treatment in a boy with glutathione synthetase
      deficiency.
AB  - We report a 3-year-old boy with glutathione synthetase deficiency, who in the
      newborn period developed severe persistent haemolytic anaemia. Treatment with
      erythropoietin was introduced with good clinical and haematological response.

PMID- 16435215
TI  - Increased HVA detected on organic acid analysis in a patient with Costello
      syndrome.
AB  - Urine organic acid analysis is routinely performed to investigate inborn errors
      of metabolism; however, interpretation can be difficult owing to the detection of
      compounds derived from other disease states or from nonpathological causes. We
      describe the finding of elevated homovanillc acid (HVA) on urine organic acid
      analysis which was not associated with medication or a neuroendocrine tumour but
      with Costello syndrome.

PMID- 16435216
TI  - Gordon syndrome and succinylcholine.
AB  - We present a case of 6-year-old boy who developed severe hyperkalaemia and
      ventricular tachycardia after administration of succinylcholine. Ventricular
      tachycardia was defibrillated and Gordon syndrome, which was diagnosed
      subsequently, was treated successfully. Paediatric patients with underlying
      metabolic disorders such as Gordon syndrome are at high risk of developing severe
      hyperkalaemia after succinylcholine administration.

PMID- 16435217
TI  - Glycerol kinase deficiency presenting with hypodipsia, osmotic diuresis and
      severe hypernatraemia.
AB  - A Chinese boy with glycerol kinase deficiency is reported. His presentation with
      severe hypernatraemia secondary to hypodipsia and glycerol-induced osmotic
      diuresis is unusual and not previously described in the literature.

PMID- 16435218
TI  - Congenital disorder of glycosylation (CDG) Ig: report on a patient and review of
      the literature.
AB  - We report a new patient with CDG Ig and review the five other known patients.
      From the data on this small number of patients, it seems that the association of
      psychomotor retardation, male hypogenitalism and decreased serum IgG in a patient
      with a type 1 pattern of serum sialotransferrins might be a clue to the diagnosis
      of CDG Ig.

PMID- 16435219
TI  - A novel deletion in a Pearson syndrome infant with hypospadias and cleft lip and
      palate.
AB  - Pearson syndrome is a rare multiorgan mitochondrial disorder that causes
      substantial disability and usually leads to premature death. We describe an
      infant with Pearson syndrome who showed, in addition to the typical features of
      the syndrome, cleft lip and palate and hypospadias.

PMID- 16435220
TI  - Methionine adenosyltransferase (MAT) I/III deficiency with concurrent
      hyperhomocysteinaemia: two novel cases.
AB  - This study reports three novel mutations of the methionine adenosyltransferase
      (MAT) lA gene and confirms that hyperhomocysteinaemia may be a characteristic
      finding in MAT I/III deficiency. Thus, MAT I/III deficiency is important in the
      differential diagnoses of hyperhomocysteinaemia, which may lead to clinical
      complications of MAT I/III deficiency.

PMID- 16435221
TI  - Search for mutations in SLC1A5 (19q13) in cystinuria patients.
AB  - To elucidate whether SLC1A5 is involved in the aetiology of cystinuria, we
      screened two non-type I cystinuria families without detectable mutations inSLC7A9
      (and SLC3A1) but compatible with linkage to 19q13 for genomic variants in SLC1A5.
      Despite evidence for an involvement of SLC1A5 in the aetiology of cystinuria, we
      could not identify any mutation in this gene in the two families. With SLC1A5, a
      further candidate gene for cystinuria can be excluded as being involved in the
      pathogenesis of this disease in these two families. Of course, there remains the
      possibility that other genes are involved in cystinuria; further molecular
      studies will clarify the complex nature of this disorder.

PMID- 16435222
TI  - Normal very-long-chain fatty acids in peroxisomal D-bifunctional protein
      deficiency: a diagnostic pitfall.
AB  - We present a relatively mild case of peroxisomal D-bifunctional protein
      deficiency with inconsistent screening results in plasma for peroxisomal
      disorders.

PMID- 16435223
TI  - Mutational spectrum in ten Italian patients affected by methylmalonyl-CoA mutase
      deficiency.
AB  - We report seven novel mutations, including three amino acids substitutions
      (p.Glu286Lys, p.Cys560Tyr, p.Pro615Leu), two nonsense mutations (p.Arg31X, p.Glu
      451X), one splicing defect (c.2125-1G >A), one small deletion (c.1758-1759delA)
      and nine previously described mutations identified in 10 unrelated Italian
      patients affected by mut MMA.

PMID- 16435224
TI  - Methylmalonic aciduria: follow-up and enzymology on the original case after 36
      years.
AB  - A 36-year follow-up on the original patient described with methylmalonic aciduria
      has shown that she has methylmalonyl-CoA apomutase deficiency. The main clinical
      problem associated with her methylmalonic aciduria is progressive renal
      impairment requiring commencement of haemodialysis at 42 years of age.

PMID- 16435225
TI  - Influence of D-arabitol and ribitol on neuronal network activity.
AB  - To date, two new defects in the pentose phosphate pathway have been identified in
      patients with abnormalities in their polyol profiles. Some of them presented with
      neurological symptoms of so far unknown aetiology. The pathophysiological role of
      polyols, e.g. in the brain, is relatively unknown. We tested the neurotoxicity of
      polyols using a 'neurochip' model. After exposure of cortical rat neurons to D
      arabitol and ribitol in increasing concentrations up to 10 mmol/L, the
      electrophysiological activity was measured. No acute effect on the spontaneous
      network activity of cortical neurons was observed. We speculate that polyols have
      only secondary effects on brain dysfunction.

PMID- 16435226
TI  - Genetic variants of transferrin in the diagnosis of protein hypoglycosylation.
AB  - Human transferrin (Tf) shows genetic polymorphisms, which may interfere in the
      screening of congenital disorders of glycosylation (CDG). Isoelectric focusing
      followed by direct immunofixation was used for Tf analysis in controls and
      several groups of patients. Equivocal results in one case have been recognized as
      a rare Tf CD variant. A higher incidence of some genetic variants has been
      reported in connection with certain diseases; of the seven Tf phenotypes detected
      in our set of samples, an apparently higher frequency of Tf C1C2 variant found in
      some groups of patients was not significant.

PMID- 16435227
TI  - Congenital disorder of glycosylation type Ia in a 6-year-old girl with a mild
      intellectual phenotype: two novel PMM2 mutations.
AB  - We report two novel mutations in the PMM2 gene in a girl with congenital disorder
      of gylcosylation type Ia (CDG Ia) and a mild intellectual phenotype.

PMID- 16435228
TI  - Smith-Lemli-Opitz syndrome with a classical phenotype, oesophageal achalasia and
      borderline plasma sterol concentrations.
AB  - The diagnostic biochemical hallmarks of Smith-Lemli-Opitz syndrome (SLOS) are
      elevated concentrations of the cholesterol precursors 7- and 8-dehydrocholesterol
      (7- and 8-DHC). We describe a patient with classical SLOS phenotype and
      oesophageal achalasia, which has not been reported in SLOS patients before.
      Plasma 7-DHC and 8-DHC were only marginally elevated. The diagnosis was confirmed
      by sterol analysis in cultured skin fibroblasts and mutation analysis.

PMID- 16435229
TI  - Elevation of plasma aspartylglucosaminidase is a useful marker for the congenital
      disorders of glycosylation type I (CDG I).
AB  - Elevated plasma aspartylglucosaminidase activity was found in 21/25 cases of CDG
      Ia, in single cases of CDG Ib, Ic and If, and in 15/16 cases of CDG Ix. The CDG I
      patients in whom the activity was not raised were either atypical clinically (CDG
      Ia) or very young (CDG Ih).

PMID- 16435233
TI  - [A treatment concept].

PMID- 16435237
TI  - [Gastrointestinal stromal tumors].

PMID- 16435246
TI  - [Ultrasound contrast media--principles and clinical applications].
AB  - This article reviews the technical basics and the application of contrast
      enhanced ultrasonography. Ultrasound contrast agents have been evaluated in
      various organs and have proven to be particularly useful in the detection and
      characterization of liver lesions. Experiences in small parts (such as breast, or
      lymph nodes) are so far limited, because only since recently are the technical
      prerequisites available for contrast-enhanced ultrasound high-frequency
      transducers. Ultrasound contrast media can be used for functional studies, e. g.,
      of organ or tumor perfusion. Mathematical models were primarily developed for
      measuring myocardial perfusion and have recently been adapted for studying
      tumors. In animal experiments as well as in clinical applications, quantitative
      parameters of tumor perfusion have been evaluated as surrogate parameters for
      response to radiotherapy, chemotherapy, or treatment with anti-angiogenic agents.

PMID- 16435247
TI  - [Sonography of the scrotum].
AB  - Ultrasonography (US) has become the method of choice for imaging in diseases
      affecting the scrotum. With the development of high resolution transducers using
      colour Doppler and pulsed Doppler, it is now possible to make accurate diagnoses.
      Sonography is able to distinguish immediately between intra- and extratesticular
      lesions. It is also possible to differentiate between cystic and solid tumours.
      Solid testicular tumours may be detected without difficulty and thus the
      patient's dignity is practically assured (98 % of solid testicular tumours are
      malignant). In cases of acute diseases of the scrotum, sonography nearly always
      permits a differentiation between torsion and inflammation, thus avoiding the
      risk of unnecessary operations. The review covers the introduction, anatomy, the
      scanning protocol for scrotal ultrasound and pathological changes. Testicular
      tumours and torsion are discussed in detail. Variations from the norm and
      pitfalls are outlined so as to help avoid making misdiagnoses.

PMID- 16435248
TI  - Impact of ECG gating in contrast-enhanced MR angiography for the assessment of
      the pulmonary veins and the left atrium anatomy.
AB  - PURPOSE: Implementation of ECG gating in contrast-enhanced MR angiography (ceMRA)
      for improved visualization of the pulmonary veins, the left atrium, and the
      thoracic vessels. MATERIALS AND METHODS: CeMRA was performed on twelve patients
      with a history of recurrent atrial fibrillation for the purpose of an intra
      individual comparison with and without ECG gating on a 1.5 Tesla MR system
      (Gyroscan Intera, Philips Medical Systems, Best, NL). Objective image quality
      parameters such as the signal-to-noise ratio (SNR) of the blood and the contrast
      to-noise ratio (CNR) between the blood and myocardium or lung parenchyma were
      analyzed. The contour sharpness of the pulmonary veins, left atrium, ascending
      aorta, and pulmonary trunk was also measured. In addition, the artifact level was
      subjectively assessed by two observers blinded with respect to the sequence
      parameters. Statistically significant differences (p < 0.05) between the
      procedures were analyzed using the Wilcoxon test and Pearson Chi-square test.
      RESULTS: The use of ECG gating in ceMRA significantly reduced artifacts caused by
      cardiac motion and vessel pulsation. This in turn lead to a significant increase
      in the contour sharpness of the left atrium and the thoracic vessels. In
      addition, higher SNR and CNR were found using ECG-gated ceMRA compared to
      standard ceMRA. CONCLUSION: The use of ECG gating in ceMRA results in artifact
      free and sharper delineation of the structures of the heart and thoracic vessels.

PMID- 16435249
TI  - [Radiation dose of the radiologist and the assistant in transarterial hepatic
      chemoembolization--comparison with the dose limits].
AB  - PURPOSE: To determine the values of effective dose and partial body dose for the
      radiologist and the assistant during transarterial chemoembolization (TACE) of
      hepatocellular carcinoma (HCC) und to compare the doses with the dose limits.
      MATERIALS AND METHODS: In 65 TACE of HCC cases, values of various surface doses
      for the radiologist and the assistant were measured. The measurements were
      performed with the help of thermoluminescence dosemeters (TLD) that were attached
      to the eyebrows, over the lobes of the thyroid gland, to the breasts, abdomen and
      symphysis, and to the hands and the lower legs. The measured surface dose values
      were used as indicators of the exposure of the organs and tissues located near
      the surface, i. e. eye lens, thyroid gland, breast, testes and tibia. They were
      also seen as conservative estimations of tissues deep inside the body and the
      extremities. RESULTS: The highest surface dose for the radiologist was measured
      at the lower leg (0.58 +/- 0.28 mSv) and the highest surface dose for the
      assistant was measured at the right lower leg (0.24 +/- 0.20 mSv) since it was
      closer to the tube than the left side, followed by the dose values at the also
      unprotected areas of the eyebrows, lobes of the thyroid gland and the hands. The
      estimated value of the effective dose was 0.06 +/- 0.03 mSv for the radiologist
      and 0.04 +/- 0.01 mSv for the assistant. With regard to the relationship between
      the dose limits according to the German X-ray regulation and the measured values
      and with regard to the maximum possible number of interventions per year, the
      partial body dose of the red bone marrow in the lower leg provided the greatest
      limitation, followed by the partial body dose of the muscle in the lower leg and
      the effective dose. CONCLUSION: In order to meet the dose limits, especially the
      lower leg should be protected, and the effective dose should also be reduced.

PMID- 16435250
TI  - [Quality control of thoracic X-rays in children in diagnostic centers with and
      without pediatric-radiologic competence].
AB  - PURPOSE: Radiation protection in pediatric radiology is very important because of
      the particular sensitivity of radiosensitive organs in younger patients.
      Optimized image quality supports radiation protection and should be targeted. In
      our study we examined the quality of pediatric chest X-rays at diagnostic centers
      (university hospitals and other large clinics). We then evaluated differences in
      image quality in departments without pediatric competence (R) and departments
      with pediatric competence (PR). MATERIALS AND METHODS: Our study was based on 313
      conventional chest X-rays from 207 patients (192 p. a./a. p. and 121 lateral, 43
      from R, 258 from PR and 12 neither from R nor KR) and 38 digital chest X-rays
      from 26 patients (25 p. a./a. p. and 13 lateral, 1 from R and 37 from PR). All
      patients (age 0 - 18 years) are from Nephroblastoma-Study SIOP-93/01-GPOH. We
      examined all initial chest X-rays, which were sent to us for evaluation upon
      request between 4/3/2002 and 6/14/2002. The examined parameters were: exposure,
      centering of the X-rays/patient positioning, collimation and sharpness. The X
      rays were evaluated on a scale from 1 (best result) to 5 (worst result),
      resulting in an overall score of A = optimum, B = minor problems, C = major
      problems, or D = unusable. The optical density, the center of the image and the
      relative field size were also measured. Statistical tests (Mann-Whitney-U and log
      regression) were carried out on the conventional images. The study was performed
      retrospectively. The exposure, sharpness and optical density of the digital X
      rays were not analyzed. RESULTS: In the case of all conventional X-rays, the
      quality of the centering of the X-rays/patient positioning and collimation was
      moderate (average scale value: 2.4 and 2.8), and the quality of the exposure and
      sharpness was good and very good (average scale value: 1.9 and 1.5). The quality
      of the chest X-rays in departments with additional pediatric radiological
      expertise was better mainly in the case of younger patients (younger than 5
      years) than departments without additional pediatric radiological expertise
      (average scale value in age group 0 - 1 month: PR = 1.7; average scale value in
      age group 2 months - 2 years: R = 2.4 and PR = 1.8; average scale value in age
      group 3 - 5 years: R = 2.5 and PR = 1.8). CONCLUSION: Despite the good overall
      image quality, the quality of the centering of the X-rays/patient positioning and
      collimation was insufficient in both examiner groups (R and PR). For this reason,
      some radiation protection requirements could not be fulfilled. X-rays from PR
      were higher quality than X-rays from R in this special study group. Day-to-day
      quality checks are necessary for pediatric chest X-rays in order to achieve a
      high quality standard.

PMID- 16435251
TI  - [MRI of arthritis with the USPIO SH U 555 C: optimization of T1 enhancement].
AB  - PURPOSE: To optimize contrast agent dose and pulse sequence parameters in order
      to achieve a maximal T1 enhancement in arthritic knee joints with ultra small
      superparamagnetic iron oxides (USPIO)-enhanced MRI. MATERIALS AND METHODS:
      Antigen-mediated arthritis was induced in the right knee of nine Sprague Dawley
      rats. The arthritic knee joint as well as the contralateral normal knee were
      investigated in a 2 Tesla MR scanner before as well as in short intervals up to 2
      h after USPIO injection, using T1-weighted gradient echo (GE) sequences. Three
      rats each received intravenous injections of the new USPIO SHU 555 C (SH U 555 C,
      Schering AG, Berlin) at doses of 40, 100 and 200 micromol Fe/kg. Pulse sequence
      parameters of the GE-sequence were optimized by varying flip angles (alpha) and
      echo times (TE). Changes in signal intensities (SI) of the arthritic knee and
      contralateral normal knee were quantified as DeltaSI (%) = /([SIpost - SIpre] /
      SIpre) x 100 %/ and compared with histopathology. RESULTS: Histology of the
      arthritic knees demonstrated a marked inflammatory proliferation of the synovium.
      The USPIO SH U 555 C caused a significant increase in signal intensity of the
      arthritic joints on T1-weighted MR images (p < 0.05). This effect was optimized
      using a flip angle of 60-70 degrees, a minimal TE and a dose of 200 micromol
      Fe/kg. Visually the contralateral normal knee did not show any USPIO enhancement.
      CONCLUSION: Inflammation can be depicted with marked T1 enhancement by the USPIO
      SH U 555 C using high contrast agent doses and optimized MR pulse sequence
      parameters.

PMID- 16435252
TI  - [Balloon-assisted percutaneous vertebroplasty in patients with osteoporotic
      vertebral body compression fractures--first results].
AB  - PURPOSE: To determine the feasibility, efficacy and safety of balloon-assisted
      percutaneous vertebroplasty (BA-VP) in patients with osteoporotic vertebral
      compression fractures (VCFs). MATERIALS AND METHODS: In 47 patients (29 women, 18
      men; mean age: 70 years and 4 months) with severe VCFs, 66 BA-VPs were performed
      via a unipedicular access. After initial puncture (under combined fluoroscopy and
      CT guidance) of the vertebral body (VB), the needle was retraced by 1.5 cm, and a
      12-mm Fogarty balloon catheter was introduced and inflated using 2-4 ml diluted
      contrast media (CM). After the subsequent removal of the catheter and
      repositioning of the needle, vertebroplasty was performed. RESULTS: The mean
      volume of PMMA injected was 4.4 ml (2.5-7.2 ml). Pain reduction (measured by the
      Visual Analogue Scale) was achieved in 95 % of the patients, dropping from on
      average 8.0 pre-intervention to 2.2 after a mean follow-up of 8 months. A
      reduction of the pain relieving medication was achieved in 68 % of the cases and
      patient activity improved markedly. No severe or clinically relevant
      complications were observed. Cement leakage occurred by filling of epidural and
      paravertebral veins in 9.1 and 6.1 % of the cases, respectively. Leakage into the
      paravertebral soft tissues was seen in 3.0 % of the patients and to the adjacent
      disc space in 10.6 % of the cases. CONCLUSION: Vertebroplasty and kyphoplasty are
      currently used to treat osteoporotic VCFs but show either a comparatively high
      leakage rate or are rather complex and expensive. Balloon-assisted vertebroplasty
      seems to combine advantages from both methods and is effective, safe and
      comparatively inexpensive.

PMID- 16435253
TI  - [Intravascular optical coherence tomography: differentiation of atherosclerotic
      plaques and quantification of vessel dimensions in crural arterial specimens].
AB  - PURPOSE: Intravascular optical coherence tomography (OCT) is a new technique
      based on infrared light that visualizes the arteries with a resolution of 10-20
      microm. Intravascular ultrasound (IVUS) is the current in vivo reference standard
      and provides a resolution of 100-150 microm. This study compared OCT to IVUS and
      histopathology with respect to the ability to differentiate atherosclerotic
      plaques and quantify vascular dimensions in peripheral crural arteries ex vivo.
      MATERIALS AND METHODS: 50 segments of atherosclerotic arteries derived from five
      amputated human lower extremities were examined. The different plaque types
      (fibrous, high-lipid content, calcified) were assigned by two independent
      examiners, and the sensitivity and specificity of OCT in comparison with
      histopathology as well as intra- and interobserver consensus were calculated. A
      comparison of OCT with IVUS addressed the parameters: luminal area (LA), vascular
      wall area (VA) and plaque area (PA). RESULTS: When comparing OCT and
      histopathology with respect to the differentiation of various plaque types,
      sensitivities of 81 % and specificities of 89 % for fibrous plaques, of 100 % and
      93 % for lipid-rich plaques and of 80 % and 89 % for calcified plaques were
      achieved (overall correlation 83 %). Intra- and interobserver consensus was very
      high (kappa = 0.86 and kappa = 0.89, p < 0.001, respectively). There was also a
      high correlation between quantitative measurements (Bland-Altman plot [LA]: mean
      bias, 0.1 mm(2) accuracy +/- 1.8 mm(2), r = 0.95 [p < 0.001] Bland-Altman plot
      [VA]: mean bias, 0.3 mm(2) accuracy +/- 2.3 mm(2), r = 0.94 [p < 0.001] Bland
      Altman plot [PA]: mean bias, 0.4 mm(2) accuracy +/- 2.3 mm(2), r = 0.80 [p <
      0.01]. CONCLUSION: OCT allows the differentiation of atherosclerotic plaque types
      in crural arteries with high accuracy compared to histopathology. Quantitative
      measurements show a high correlation with IVUS, the current reference standard.

PMID- 16435254
TI  - [Diagnostic mode and tumor staging of breast cancers in the setting of
      opportunistic screenings].
AB  - PURPOSE: To analyze data at the time of diagnosis of breast cancer in three
      radiology practices in Austria in the setting of opportunistic screening.
      MATERIALS AND METHODS: In 529 women (ages 31 - 89, mean age 61.1) with breast
      cancer, the mode of diagnosis (detected clinically or by opportunistic
      screening), the local tumor stages, and intervals between screening examinations
      were assessed. RESULTS: In 33.6 % (178 of 529) of the cases, the breast cancer
      was detected clinically, and in 66.4 % (351 of 529) of the cases, the cancer was
      detected by opportunistic screening. Cancers in prognostically favorable stages
      (in situ carcinomas, pT1 a, pT1 b, pT1c) were detected by opportunistic screening
      in 79.9 % of the cases. The clinically detected cancers were in locally advanced
      stages (pT2, pT3) in 58.4 % of the cases. In the majority of clinically detected
      cases (75 %), the women had never had a mammogram before or had not had a recent
      one. In 13 % of the cases detected by opportunistic screening, diagnosis was made
      during the first exam, in 40 % of the cases, the period since the last mammogram
      was less than 24 months, and in 47 % of the cases, this period was greater than
      24 months. CONCLUSION: In our patients the majority of breast cancers were
      detected in early stages by opportunistic screening. The use of an organized
      system with exams at regular intervals may further reduce the number of advanced
      cancers.

PMID- 16435255
TI  - [Pulmonary nocadiosis with cerebral spreading].

PMID- 16435256
TI  - [Herniation of the heart after pneumonectomy--rare, but life threatening].

PMID- 16435257
TI  - [Ureteral erosion with massive hematuria after femoral artery bifurcation
      prosthesis].

PMID- 16435258
TI  - [Ruptured renal tumor as a rare differential diagnosis of colicky abdominal
      pain].

PMID- 16435259
TI  - [Paradoxical embolism in the carotid artery communis: incidental discovery in CT
      angiography of the pulmonary artery].

PMID- 16435260
TI  - [Cervical cerebrospinal fluid fistula after whiplash injury--treatment using CT
      guided autologous blood injection].

PMID- 16435264
TI  - Fine-Tuning Plant Defence Signalling: Salicylate versus Jasmonate.
AB  - Plant defences against pathogens and herbivorous insects form a comprehensive
      network of interacting signal transduction pathways. The signalling molecules
      salicylic acid (SA) and jasmonic acid (JA) play important roles in this network.
      SA is involved in signalling processes providing systemic acquired resistance
      (SAR), protecting the plant from further infection after an initial pathogen
      attack. SAR is long-lasting and provides broad spectrum resistance to biotrophic
      pathogens that feed on a living host cell. The regulatory protein NPR1 is a
      central positive regulator of SAR. SA-activated NPR1 localizes to the nucleus
      where it interacts with TGA transcription factors to induce the expression of a
      large set of pathogenesis-related proteins that contribute to the enhanced state
      of resistance. In a distinct signalling process, JA protects the plant from
      insect infestation and necrotrophic pathogens that kill the host cell before
      feeding. JA activates the regulatory protein COI1 that is part of the E3
      ubiquitin ligase-containing complex SCFCOI1, which is thought to derepress JA
      responsive genes involved in plant defence. Both synergistic and antagonistic
      interactions have been observed between SA- and JA-dependent defences. NPR1 has
      emerged as a critical modulator of cross-talk between the SA and JA signal and is
      thought to aid in fine tuning defence responses specific to the encountered
      attacker. Here we review SA- and JA-dependent signal transduction and summarize
      our current understanding of the molecular mechanisms of cross-talk between these
      defences.

PMID- 16435265
TI  - Interactions between drought and O3 stress in forest trees.
AB  - Temperature increase and altered precipitation are facets of "Global Change",
      along with enhanced tropospheric ozone (O3) and CO2 levels. Both O3 and drought
      may curtail the probably limited capacity of "extra" carbon fixation in forest
      trees under a CO2-enriched atmosphere. In view of the exceptionally dry year of
      2003 in Central Europe, this mini-review highlights O3/drought interactions in
      biochemical and ecophysiological responses of trees. Such interactions appear to
      vary, depending on the genotype and factorial scenarios. If O3 perturbs stomatal
      regulation, tolerance to both drought and persisting O3 exposure may be weakened,
      although drought preceding O3 stress may "harden" against O3 impact. Stomatal
      closure under drought may shield trees against O3 uptake and injury, which indeed
      was the case in 2003. However, the trees' "tuning" between O3 uptake and defence
      capacity is crucial in stress tolerance. Defence may be constrained due to
      limited carbon fixation, which results from the trade-off with O3 exclusion upon
      stomatal closure. Drought may cause a stronger reduction in stem growth than does
      ozone on an annual basis.

PMID- 16435266
TI  - Deletion of core components of the plastid protein import machinery causes
      differential arrest of embryo development in Arabidopsis thaliana.
AB  - Among the genes that have recently been pinpointed to be essential for plant
      embryo development a large number encodes plastid proteins suggesting that
      embryogenesis is linked to plastid localized processes. However, nuclear encoded
      plastid proteins are synthesized as precursors in the cytosol and subsequently
      have to be transported across the plastid envelopes by a complex import
      machinery. We supposed that deletion of components of this machinery should allow
      a more general assessment of the role of plastids in embryogenesis since it will
      not only affect single proteins but instead inhibit the accumulation of most
      plastid proteins. Here we have characterized three Arabidopsis thaliana mutants
      lacking core components of the Toc complex, the protein translocase in the outer
      plastid envelope membrane, which indeed show embryo lethal phenotypes.
      Remarkably, embryo development in the atToc75-III mutant, lacking the pore
      forming component of the translocase, was arrested extremely early at the two
      cell stage. In contrast, despite the complete or almost complete lack of the
      import receptors Toc34 and Toc159, embryo development in the a tToc33/34 and
      atToc132/159 mutants proceeded slowly and was arrested later at the transition to
      the globular and the heart stage, respectively. These data demonstrate a strict
      dependence of cell division and embryo development on functional plastids as well
      as specific functions of plastids at different stages of embryogenesis. In
      addition, our analysis suggest that not all components of the translocase are
      equally essential for plastid protein import in vivo.

PMID- 16435267
TI  - High-light stress does not impair biomass accumulation of sun-acclimated tropical
      tree seedlings (Calophyllum longifolium Willd. and Tectona grandis L. f.).
AB  - Studies with seedlings of tropical rainforest trees ( Calophyllum longifolium
      Willd.; Tectona grandis L. f.) were designed to test whether high-light stress
      affects photosynthetic performance and growth. Seedlings were cultivated in pots
      at a field site in Central Panama (9 degrees N) and separated into two groups:
      (1) plants exposed to full solar radiation; (2) plants subjected to automatic
      neutral shading (48 %) whenever visible irradiance surpassed 1000, 1200, or 1600
      micromol photons m-2 s-1. After 2-4 months, chlorophyll fluorescence (Fv/Fm
      ratio), photosynthetic net CO2 uptake, pigment composition, alpha-tocopherol
      content of leaves, and plant biomass accumulation were measured. Fully sun
      exposed, compared to periodically shaded plants, experienced substantial high
      light stress around midday, indicated by photoinhibition of photosystem II and
      depressed net CO2 uptake. Higher contents of xanthophyll cycle pigments, lutein,
      and alpha-tocopherol showed an enhancement of photoprotection in fully sun
      exposed plants. However, in all experiments, the maximum capacity of net CO2
      uptake and plant dry mass did not differ significantly between the two
      treatments. Thus, in these experiments, high-light stress did not impair
      productivity of the seedlings studied. Obviously, the continuously sun-exposed
      plants were capable of fully compensating for any potential costs associated with
      photoinhibition and repair of photosystem II, reduced CO2 assimilation, and
      processes of high-light acclimation.

PMID- 16435268
TI  - Parameters for cellular viability and membrane function in chenopodium cells show
      a specific response of extracellular pH to heat shock with extreme Q10.
AB  - The effect of brief heat shock on Chenopodium cells was investigated by measuring
      biochemical parameters for cellular vitality, membrane function and integrity:
      extracellular pH, release of osmotic compounds, phosphatase, protein and
      betalain, and cellular reduction of DCPIP and MTT. A threshold temperature was
      found at 45 degrees C, where release of osmotic compounds, protein and betalain,
      and reduction of DCPIP and MTT indicate loss of vitality. Extracellular pH and an
      alkaline phosphatase responded 10-20 degrees C below this threshold, suggesting
      that extracellular alkalinization, and probably the release of a phosphatase, are
      part of a specific cellular response to abiotic stress induced by heat shock. The
      extracellular proton concentration did not increase above 45 degrees C: this may
      indicate equilibration of gradients driving this process or an inactivation of
      cellular mechanisms responsible for extracellular alkalinization. The response of
      extracellular pH to heat shock in Chenopodium cell suspensions was fast, i.e., up
      to +1 pH in 5 min. Addition of the K+/H+ antiporter nigericin to Chenopodium
      cells caused an extracellular alkalinization similar to heat shock. The heat
      shock-induced extracellular alkalinization was characterized by Q10 values for
      distinct ranges of temperature (Q10 of 56 for 24-31 degrees C, 2.3 for 31-42
      degrees C, and 1.0 for 42-50 degrees C). To the author's knowledge, the Q10 of 56
      is the highest found up to now. These results suggest that extracellular protons
      are involved in temperature sensing and signalling in plant cells, probably via a
      channel-mediated pathway.

PMID- 16435269
TI  - Physiological performance of beech (Fagus sylvatica L.) at its southeastern
      distribution limit in Europe: seasonal changes in nitrogen, carbon and water
      balance.
AB  - To assess the physiological performance of drought-sensitive European beech (
      Fagus sylvatica L.) under the dry Mediterranean climate prevailing at its
      southeastern distribution limit in Europe, we analyzed seasonal changes in
      carbon, nitrogen and water balance of naturally grown adult trees. We determined
      the foliar C and N contents, delta13C and delta18O signatures, total soluble non
      protein nitrogen compounds (TSNN) in xylem, leaves, and phloem, as well as leaf
      water potential and photosynthetic quantum yield in northern Greece during 2003.
      Tissue sampling was performed in May, July, and September, while field
      measurements were conducted regularly. Climatic conditions for the 2003 growing
      season fall within the typical range of the studied area. The N- and C-related
      parameters displayed distinct seasonal courses. TSNN was highest in May in all
      tissues, and asparagine (Asn) was then the most abundant compound. Thereafter,
      TSNN decreased significantly in all tissues and both its concentration and
      composition remained constant in July and September. In both months, glutamate
      (Glu) prevailed in leaves, gamma-aminobutyric acid (GABA) in phloem exudates from
      twigs and trunks, and arginine (Arg) in the xylem sap, where loading with amino
      acids was rather low during that period, amounting to only 0.8 micromol N ml-1 in
      September. Highest total foliar N and C contents were detected in May, and the
      elevated abundance of nutrients as well as an increased foliar delta13C signature
      at the beginning of the growing season is attributed to remobilization processes.
      The signatures of delta18O, quantum yield and leaf water potentials varied only
      slightly throughout the growing season. Although summer precipitation at the
      study site was considerably lower compared to what is usual for typical central
      European beech forests, no intensive drought responses of the physiological
      apparatus were detected in the studied beech trees. This suggests efficient
      internal regulation mechanisms, constantly ensuring a favourable physiological
      status under the relatively dry Mediterranean climate.

PMID- 16435270
TI  - Cadmium hyperaccumulation and reproductive traits in natural Thlaspi caerulescens
      populations.
AB  - During the last decade, the metal hyperaccumulating plants have attracted
      considerable attention because of their potential use in decontamination of heavy
      metal contaminated soils. However, in most species, little is known regarding the
      function, the ecological and the evolutionary significances of hyperaccumulation.
      In our study, we investigated the parameters influencing the Cd concentration in
      plants as well as the biological implications of Cd hyperaccumulation in nine
      natural populations of Thlaspi caerulescens. First, we showed that Cd
      concentration in the plant was positively correlated with plant Zn, Fe, and Cu
      concentrations. This suggested that the physiological and/or molecular mechanisms
      for uptake, transport and/or accumulation of these four heavy metals interact
      with each other. Second, we specified a measure of Cd hyperaccumulation capacity
      by populations and showed that T. caerulescens plants originating from
      populations with high Cd hyperaccumulation capacity had better growth, by
      developing more and bigger leaves, taller stems, and produced more fruits and
      heavier seeds. These results suggest a tolerance/disposal role of Cd
      hyperaccumulation in this species.

PMID- 16435271
TI  - Ploidy level variability in South American fescues (festuca L., poaceae): use of
      flow cytometry in up to 5 1/2-year-old caryopses and herbarium specimens.
AB  - Ploidy levels and chromosome numbers for 24 species of Festuca L. from 29 sites
      in Bolivia, Colombia, Ecuador and Venezuela are given. The ploidy level of 22
      species is reported for the first time. A higher proportion of tetraploids in
      northern South America and the high frequency of polyploids in the whole
      continent are documented. In combination with chromosome counts, ploidy level was
      determined using flow cytometry in 4- to 5 1/2 -year-old herbarium specimens and
      mature caryopses. Flow cytometric determination from seeds was more reliable than
      determination from herbarium specimens. In herbarium specimens, the youngest,
      fresh green leaves, still hidden in sheaths, seem to be most suitable for
      cytometric determination. In old, brownish leaves, or poorly preserved herbarium
      specimens, the degradation of DNA signal in flow histograms was documented. DNA
      content measured in seeds was always higher than that measured in herbarium
      specimens, which may be caused by the presence of different cytosolic compounds.
      Differences of about 15% in relative DNA content of F. sodiroana and F. vaginalis
      was found in simultaneous measurements in seeds.

PMID- 16435272
TI  - Genetic diversity, population structure, and conservation of Sophora
      moorcroftiana (Fabaceae), a shrub endemic to the Tibetan Plateau.
AB  - Sophora moorcroftiana is a perennial leguminous low shrub endemic to the middle
      reaches of Yarlung Zangbo River in Tibet. It is an important species to fix sand
      dunes and to avoid the formation of shifting sands; therefore, its progressive
      over-exploitation may enhance land desertification. The levels and distribution
      of genetic variability of this species were evaluated from 10 natural populations
      at 24 loci encoding 13 enzymes, using allozyme analysis by starch gel
      electrophoresis. Data obtained revealed moderate levels of genetic variation
      within populations (Pp=27.5%, Ap=1.5, Hep=0.122) and a considerable divergence
      among populations (FST=0.199). Significant positive correlations (r2=0.49,
      p<0.05; r2=0.46, p<0.05) were found between elevation and both mean number of
      alleles per locus (A) and gene diversity (He) in the studied populations of S.
      moorcroftiana. Lower genetic diversity in lower elevation populations might be
      due to the negative effects of human pressures and habitat fragmentation, to
      adaptation to high altitudes as a consequence of a peripatric speciation process,
      or to directional gene flow along the river basin from the source populations
      located in the west at higher altitudes. The evaluation of the degree of threat
      has led to the inclusion of this species in the category of EN ("endangered"),
      and conservation strategies for this endemic species are discussed on the basis
      of these findings.

PMID- 16435273
TI  - Phylogeny of the genus Peperomia (Piperaceae) inferred from the trnK/matK region
      (cpDNA).
AB  - The genus Peperomia is one of the largest genera of basal angiosperms, comprising
      about 1500-1700 pantropically distributed species. The currently accepted
      infrageneric classification divides Peperomia into nine subgenera and seven
      sections. This classification is based on some 200 species, primarily using fruit
      morphology. The monophyly of these infrageneric taxa has never been tested and
      molecular phylogenetic studies of a representative sampling within Peperomia do
      not exist. This paper provides the first molecular phylogeny for the genus
      Peperomia. Monophyletic clades within Peperomia are identified and previously
      used morphological characters are critically reviewed. We show that the
      importance of some morphological characters has been overestimated and that some
      of these characters presumably have evolved several times independently. Only one
      previously described subgenus has been confirmed to be monophyletic.

PMID- 16435274
TI  - Costs of reproduction as related to the timing of phenological phases in the
      dioecious Shrub Pistacia lentiscus L.
AB  - Females of woody dioecious species usually devote more resources to reproduction
      than males. This may lead to a decrease in female survival and growth. The costs
      of reproduction, however, can be lightened through a number of mechanisms, as for
      example avoiding the temporal coincidence of reproduction and vegetative growth.
      The aim of this study was to evaluate whether males and females of P. lentiscus
      differ in the timing of their vegetative growth, and to assess whether the
      sequencing of vegetative growth and reproduction reduces reproductive costs. We
      monitored phenology in males and females. We also compared male and female
      allocation of nutrients and biomass in the branch, and the developmental
      stability of the growing shoots. We did this both prior to and at the end of the
      fruiting period. Males and females showed similar vegetative and flowering
      phenologies. Males invested more biomass in flowering, but the sexes showed equal
      vegetative biomass and nutrient content prior to the fruiting period. In female
      branches, no trade-off was found between fruit load and current-year vegetative
      growth. In P. lentiscus, avoiding the overlap of flowering, vegetative growth and
      fruiting probably contributes to reduce the immediate costs of reproductive
      efforts, both in males and females.

PMID- 16435275
TI  - Variability in fruit and seed morphology among and within populations of
      Plathymenia (Leguminosae-Mimosoideae) in areas of the Cerrado, the Atlantic
      forest, and transitional sites.
AB  - Plathymenia reticulata is a tree species that occurs in two different Brazilian
      biomes, the Cerrado (a savannah environment), and the Atlantic Forest. In the
      present study, we evaluated morphological variation within and among five
      populations located in these vegetation types and in transitional sites in order
      to test the hypothesis that habitat selective pressures, being different in the
      Cerrado and the Atlantic Forest, would cause adaptive differences in
      morphological traits in individuals occurring under these different
      circumstances. Thirteen morphological traits of fruits, seeds, and of the
      membranous endocarp were obtained from 30 fruits and 20 seeds from each of nine
      to 10 individuals per population. Significant variation was found for all traits
      while comparing individuals within populations, and most traits varied
      significantly among populations as well. Some traits differed significantly
      between forest and Cerrado populations, while transition sites showed
      intermediate patterns and higher within-population variation. Contrary to our
      hypothesis, variation in seed size and mass among populations from different
      habitats was not significant. However, as predicted, the membranous endocarp was
      shorter for the seeds from Cerrado populations than from the Atlantic Forest.
      These data suggest the existence of P. reticulata ecotypes from Cerrado and
      Atlantic Forest; the relevance to Plathymenia evolution and to its wide
      ecological distribution is discussed.

PMID- 16435276
TI  - Evolution of funnel-revolver flowers and ornithophily in nasa (loasaceae).
AB  - Floral morphology, distribution, and flower visitors for 60 taxa of Nasa are
      investigated and compared to molecular trees inferred both from a combined marker
      analysis (ITS1 and trnL (UAA)) and from a single marker (ITS1). Flowers conform
      to two different floral types: Firstly, "tilt-revolver flowers", with spreading
      to reflexed, white to yellow petals and small, brightly coloured floral scales
      contrasting with the petals and firmly enclosing the nectar (Saccatae and
      Carunculatae); secondly, "funnel-revolver flowers", with half-erect to erect,
      orange to red petals and floral scales not contrasting with the petals, or
      enclosed in the corolla, and nectar freely accessible by funnel-shaped floral
      scales ( Alatae, Grandiflorae, and N. venezuelensis species group). Phylogenetic
      analysis shows that "tilt-revolver flowers" represent the plesiomorphic condition
      by outgroup comparison. The two groups with tilt-revolver flowers in Nasa are not
      monophyletic ( Saccatae are paraphyletic, Carunculatae are polyphyletic). Most
      Saccatae fall into two monophyletic assemblages, the N. poissoniana species group
      and the N. triphylla species group. The remainder of Saccatae group either with
      Grandiflorae ( N. insignis species group) or with Alatae ( N. laxa species
      group). The clades retrieved in the molecular analysis contradict the traditional
      classification, but are congruent with vegetative morphology, details of the
      flower morphology, and biogeography. "Funnel-revolver flowers" represent the
      derived condition, but molecular data suggest a convergent development (at least
      twice independently), since the corresponding species do not constitute a
      monophyletic group. "Tilt-revolver flowers" are visited and pollinated by bees
      (especially Colletidae), whereas "funnel-revolver flowers" are mostly visited by
      hummingbirds. The transition from melittophily to ornithophily may have been the
      license for the colonization of, and the diversification in, both cloud forest
      and high Andean habitats.

PMID- 16435277
TI  - Developmental anatomy and morphology of the ovule and seed of heliconia
      (heliconiaceae, zingiberales).
AB  - The developmental anatomy and morphology of the ovule and seed in several species
      of Heliconia were investigated as part of an embryological study of the
      Heliconiaceae and to provide a better understanding of their relationships with
      the other families of the Zingiberales. Heliconia species have an ovule
      primordium with an outer integument of both dermal and subdermal origin. The
      archesporial cell is divided into a megasporocyte and a single parietal cell,
      which in turn are divided only anticlinally to form a single parietal layer,
      disintegrating later during gametogenesis. The embryo sac was fully developed
      prior to anthesis. In the developing seed, the endosperm was nuclear, with wall
      formation in the globular stage; a nucellar pad was observed during embryo
      development, but later became compressed. The ripe fruit contained seeds
      enveloped by a lignified endocarp that formed the pyrenes, with each pyrene
      having an operculum at the basal end; the embryo was considered to be
      differentiated. Most of these characteristics are shared with other Zingiberales,
      although the derivation of the operculum from the funicle and the formation of
      the main mechanical layer by the endocarp are unique to the Heliconiaceae.

PMID- 16435278
TI  - Timing of reproductive and vegetative development in Saxifraga oppositifolia in
      an alpine and a subnival climate.
AB  - Morphogenesis of floral structures, dynamics of reproductive development from
      floral initiation until fruit maturation, and leaf turnover in vegetative short
      stem shoots of Saxifraga oppositifolia were studied in three consecutive years at
      an alpine site (2300 m) and at an early- and late-thawing subnival site (2650 m)
      in the Austrian Alps. Marked differences in the timing and progression of
      reproductive and vegetative development occurred: individuals of the alpine
      population required a four-month growing season to complete reproductive
      development and initiate new flower buds, whereas later thawing individuals from
      the subnival sites attained the same structural and functional state within only
      two and a half months. Reproductive and vegetative development were not strictly
      correlated because timing of flowering, seed development, and shoot growth
      depended mainly on the date of snowmelt, whereas the initiation of flower
      primordia was evidently controlled by photoperiod. Floral induction occurred
      during June and July, from which a critical day length for primary floral
      induction of about 15 h could be inferred. Preformed flower buds overwinter in a
      pre-meiotic state and meiosis starts immediately after snowmelt in spring.
      Vegetative short-stem shoots performed a full leaf turnover within a growing
      season: 16 (+/-0.8 SE) new leaves per shoot developed in alpine and early-thawing
      subnival individuals and 12 (+/-1.2 SE) leaves in late-thawing subnival
      individuals. New leaf primordia emerged continuously from snowmelt until late
      autumn, even when plants were temporarily covered with snow. Differences in the
      developmental dynamics between the alpine and subnival population were
      independent of site temperatures, and are probably the result of ecotypic
      adaptation to differences in growing season length.

PMID- 16435279
TI  - The "Kluge-Luttge Kammer": a preliminary evaluation of an enclosed, Crassulacean
      acid metabolism (CAM) Mesocosm that allows separation of synchronized and
      desynchronized contributions of plants to whole system gas exchange.
AB  - Crassulacean acid metabolism (CAM) is recognized as a photosynthetic adaptation
      of plants to arid habitats. This paper presents a proof-of-concept evaluation of
      partitioning net CO2 exchanges for soil and plants in an arid, exclusively CAM
      mesocosm, with soil depth and succulent plant biomass approximating that of
      natural Sonoran Desert ecosystems. We present the first evidence that an enclosed
      CAM-dominated soil and plant community exposed to a substantial day/night
      temperature difference (30/20 degrees C), exhibits a diel gas exchange pattern
      consisting of four consecutive phases with a distinct nocturnal CO2 uptake. These
      phases were modulated by plant assimilation and soil respiration processes. Day
      time stomatal closure of the CAM cycle during phase III was used to eliminate
      aboveground photosynthetic assimilation and respiration and thereby to estimate
      belowground plant plus soil respiration. Rapid changes in temperature appeared to
      synchronize single plant gas exchange but individual plant gas exchange patterns
      were desynchronized at constant day/night temperatures (25 degrees C), masking
      the distinct mesocosm pattern. Overall, the mean carbon budget of this CAM model
      Sonoran Desert system was negative, releasing an average of 22.5 mmol CO2 m-2 d
      1. The capacity for nocturnal CO2 assimilation in this exclusively CAM mesocosm
      was inadequate to recycle CO2 released by plant and soil respiration.

PMID- 16435280
TI  - Hepatic stellate cells on poly(DL-lactic acid) surfaces control the formation of
      3D hepatocyte co-culture aggregates in vitro.
AB  - Evidence for the functional superiority of cells cultured as 3D aggregates or on
      3D scaffolds over conventional 2D monolayer cultures has created interest in
      material and cell based methods that influence the formation and structure of
      multicellular aggregates in vitro. We have created a co-culture of primary rat
      hepatocytes and hepatic stellate cells on a poly(DL-lactic acid) surface, a poor
      substrate for rat hepatocyte adhesion, to study the dynamics of multicellular
      spheroid formation and the resultant cell arrangement. The poly(DL-lactic acid)
      surface allows dynamic and rapid interaction of hepatocytes and stellate cells to
      form co-culture spheroids in a complex multistage process (shown by time lapse
      microscopy). This spheroid morphology supports enhanced cell viability relative
      to a mono-culture mono-layer system (measured by lactate dehydrogenase leakage).
      The distribution of the aggregating cell type in the final structure is related
      to the mechanics of formation i.e. mainly central and peripheral. This study
      provides a unique and generically applicable insight into the dynamics of
      multicellular spheroid formation where aggregation is induced by one cell type
      and imposed on another. This has implications for 3D cell culture models and a
      wide number of currently used stromal co-culture systems.

PMID- 16435281
TI  - Intranasal lipopeptide primes lung-resident memory CD8+ T cells for long-term
      pulmonary protection against influenza.
AB  - The longevity of the influenza virus-specific CD8+ T cell response following
      intranasal delivery of a synthetic lipopeptide was investigated and the
      characteristics and location of the cells associated with viral clearance
      examined. The lipopeptide, incorporating an epitope for CD8+ T cells and another
      for CD4+ T cells with the lipid moiety S-[2,3-bis(palmitoyloxy)propyl]cysteine
      (Pam2Cys) attached, induced potent and long-lived pulmonary protection. Both the
      lipopeptide and its largely unprotective non-lipidated counterpart elicited
      comparable numbers of CD8+ T cells in the spleen, which was the main location of
      the memory pool. However, the lipopeptide, unlike the non-lipidated peptide, also
      induced a substantial memory population that remained in the lungs and was
      rapidly activated upon viral challenge months later. These lipopeptide-induced
      lung-resident CD8+ T cells were also very similar in number and IFN-gamma
      secreting potential to those induced by prior exposure to the virus itself and
      are likely mediators of initial viral clearance prior to recruitment from the
      expanding lymph node T cell pool. Significant clearing responses were
      demonstrated as late as 9 months post-lipopeptide vaccination. This study shows
      that CD8+ T cells primed by the lipopeptide are not only long-lived but can take
      up residence in the lung where they are important early mediators of pulmonary
      protection.

PMID- 16435282
TI  - The absence of CCL2 expression in cervical carcinoma is associated with increased
      survival and loss of heterozygosity at 17q11.2.
AB  - To determine whether CCL2 mRNA expression is beneficial or detrimental for
      cervical cancer patients, the association between the expression of this molecule
      by cervical tumour cells, the number of tumour-associated macrophages, and
      clinicopathological parameters such as recurrence, relapse-free survival, and
      overall patient survival was investigated. In cervical cancer samples from 93
      untreated cervical cancer patients, the CCL2 mRNA expression level was quantified
      using RNA in situ hybridization and verified using real-time quantitative RT-PCR.
      The number of tumour-associated macrophages was determined using
      immunohistochemistry. Furthermore, the study investigated whether lack of CCL2
      expression was due to genetic alterations near the 17q11.2 (CCL2 genomic) region.
      CCL2 mRNA expression by cervical tumour cells was associated with the number of
      tumour-associated macrophages (p < 0.001). Lack of CCL2 mRNA expression (15
      samples; 16%) was associated with increased cumulative relapse-free survival (log
      rank test, p = 0.030), increased cumulative overall survival (log rank test, p =
      0.024), less post-operative surgery, reduced local and distant recurrence,
      reduced vascular invasion, and smaller tumour size (<40 mm). The absence of CCL2
      mRNA expression corresponded with loss of heterozygosity (LOH) at 17q11.2 in five
      of six samples. The increased cumulative relapse-free survival and cumulative
      overall survival of cervical cancer patients lacking tumour cell-associated CCL2
      mRNA suggest that the tumour-associated macrophages support tumour progression,
      presumably by promoting angiogenesis and production of growth factors.

PMID- 16435283
TI  - Down-regulation of the claudin-18 gene, identified through serial analysis of
      gene expression data analysis, in gastric cancer with an intestinal phenotype.
AB  - Gastric cancer (GC) is one of the most common malignancies worldwide. Genes whose
      expression is down-regulated in GC may be tumour suppressor genes. In the present
      study, genes with decreased expression in GC were screened for by serial analysis
      of gene expression (SAGE) data analysis and reverse transcription (RT)-polymerase
      chain reaction (PCR), and CLDN18 (encoding claudin-18) was identified.
      Quantitative RT-PCR revealed that expression of CLDN18 was down-regulated in 13
      (56.5%) of 23 GCs. Immunostaining showed that normal gastric mucosa and Paneth
      cells of the duodenum expressed claudin-18 on cell membranes. Expression of
      claudin-18 was reduced in several intestinal metaplasias of the stomach. Of 20
      samples of gastric adenoma, 18 (90.0%) showed decreased claudin-18 expression.
      Down-regulation of claudin-18 was observed in 84 of 146 GCs (57.5%) and
      correlated with poor survival in 65 advanced GCs (p = 0.0346). In addition,
      expression of the gastric and intestinal phenotypes of GC was examined by
      immunostaining for MUC5AC, MUC6, MUC2, and CD10. Of 38 GCs showing only the
      intestinal phenotype, down-regulation of claudin-18 was observed in 28 (73.7%),
      whereas in the remaining 108 GC cases, down-regulation of claudin-18 was observed
      in 56 (51.9%) (p = 0.0224). These results indicate that claudin-18 is a good
      marker of poor survival in GC. Down-regulation of claudin-18 may be involved in
      GCs with an intestinal phenotype, and may be an early event in gastric
      carcinogenesis.

PMID- 16435284
TI  - A new approach to the validation of tissue microarrays.
AB  - Although tissue microarrays (TMA) have been widely used for a number of years, it
      is still not clear how many core biopsies should be taken to determine a reliable
      value for percentage positivity or how much heterogeneity in marker expression
      influences this number. The first aim of this study was to validate the human
      visual semi-quantitative scoring system for positive staining of tumour tissue
      with the exact values determined from computer-generated images. The second aim
      was to determine the minimum number of core biopsies needed to estimate
      percentage positivity reliably when the immunohistochemical staining pattern is
      heterogeneous and scored in a non-binary way. Tissue sections from ten colorectal
      cancer specimens were stained for carbonic anhydrase IX (CA IX). The staining
      patterns were digitized and 400 artificial computer-generated images were
      generated to test the accuracy of the human scoring system. To determine the
      minimal number of core biopsies needed to account for tumour heterogeneity, 50
      (artificial) core biopsies per section were taken from the tumoural region of the
      ten digitally recorded full tissue sections. Based on the semi-quantitative
      scores from the 50 core biopsies per section, 2500 x n (n = 1-10 core biopsies)
      experimental core biopsies were then generated and scores recorded. After
      comparison with field-by-field analysis from the tumoural region of the whole
      tissue section, the number of core biopsies that need to be taken to minimize the
      influence of heterogeneity could be determined. In conclusion, visual scoring
      accurately estimated the percentage positivity and the percentage tumour present
      in a section, as judged by comparison with the artificial images. The exact
      number of core biopsies that has to be examined to determine tumour marker
      positivity using TMAs is affected by the degree of heterogeneity in the
      expression pattern of the protein, but for most purposes at least four is
      recommended.

PMID- 16435285
TI  - Interaural timing difference circuits in the auditory brainstem of the emu
      (Dromaius novaehollandiae).
AB  - In the auditory system, precise encoding of temporal information is critical for
      sound localization, a task with direct behavioral relevance. Interaural timing
      differences (ITDs) are computed using axonal delay lines and cellular coincidence
      detectors in nucleus laminaris (NL). We present morphological and physiological
      data on the timing circuits in the emu, Dromaius novaehollandiae, and compare
      these results with those from the barn owl (Tyto alba) and the domestic chick
      (Gallus gallus). Emu NL was composed of a compact monolayer of bitufted neurons
      whose two thick primary dendrites were oriented dorsoventrally. They showed a
      gradient in dendritic length along the presumed tonotopic axis. The NL and
      nucleus magnocellularis (NM) neurons were strongly immunoreactive for
      parvalbumin, a calcium-binding protein. Antibodies against synaptic vesicle
      protein 2 and glutamic acid decarboxlyase revealed that excitatory synapses
      terminated heavily on the dendritic tufts, while inhibitory terminals were
      distributed more uniformly. Physiological recordings from brainstem slices
      demonstrated contralateral delay lines from NM to NL. During whole-cell patch
      clamp recordings, NM and NL neurons fired single spikes and were doubly
      rectifying. NL and NM neurons had input resistances of 30.0 +/- 19.9 Momega and
      49.0 +/- 25.6 Momega, respectively, and membrane time constants of 12.8 +/- 3.8
      ms and 3.9 +/- 0.2 ms. These results provide further support for the Jeffress
      model for sound localization in birds. The emu timing circuits showed the
      ancestral (plesiomorphic) pattern in their anatomy and physiology, while
      differences in dendritic structure compared to chick and owl may indicate
      specialization for encoding ITDs at low best frequencies.

PMID- 16435286
TI  - Photoreceptor layer of salmonid fishes: transformation and loss of single cones
      in juvenile fish.
AB  - The retinas of many vertebrates have cone photoreceptors that express multiple
      visual pigments. In many of these animals, including humans, the original cones
      to appear in the retina (which express UV or blue opsin) may change opsin types,
      giving rise to new spectral phenotypes. Here we used microspectrophotometry and
      in situ hybridization with cDNA probes to study the distribution of UV and blue
      cones in the retinas of four species of Pacific salmon (coho, chum, chinook, and
      pink salmon), in the Atlantic salmon, and in the rainbow/steelhead trout. In
      Pacific salmon and in the trout, all single cones express a UV opsin at hatching
      (lambda(max) of the visual pigment approximately 365 nm), and these cones later
      transform into blue cones by opsin changeover (lambda(max) of the blue visual
      pigment approximately 434 nm). Cones undergoing UV opsin downregulation exhibit
      either of two spectral absorbance profiles. The first is characterized by UV and
      blue absorbance peaks, with blue absorbance dominating the base of the outer
      segment. The second shows UV absorbance diminishing from the outer segment tip to
      the base, with no sign of blue absorbance. The first absorbance profile indicates
      a transformation from UV to blue phenotype by opsin changeover, while the second
      type suggests that the cone is undergoing apoptosis. These two events
      (transformation and loss of corner cones) are closely associated in time and
      progress from ventral to dorsal retina. Each double cone member contains green
      (lambda(max) approximately 510 nm) or red (lambda(max) approximately 565 nm)
      visual pigment (double cones are green/red pairs), and, like the rods
      (lambda(max) approximately 508 nm), do not exhibit opsin changeover. Unlike
      Pacific salmonids, the Atlantic salmon shows a mixture of UV and blue cones and a
      partial loss of corner cones at hatching. This study establishes the UV-to-blue
      cone transformation as a general feature of retinal growth in Pacific salmonids
      (genus Oncorhynchus).

PMID- 16435287
TI  - Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons
      and in the peripheral nervous system.
AB  - During embryonic development, complex events, such as cellular proliferation,
      differentiation, survival, and guidance of axons, are orchestrated and regulated
      by a variety of extracellular signals. Receptor tyrosine kinases mediate many of
      these events, with several playing critical roles in neuronal survival and axonal
      guidance. It is evident that not all the receptor tyrosine kinases that play key
      roles in regulating neuronal development have been identified. In this study, we
      have characterized the spatial-temporal expression profile of a recently
      identified receptor tyrosine kinase, anaplastic lymphoma kinase (ALK), in
      embryonic chick by means of whole-mount in situ hybridization in conjunction with
      immunohistochemistry. Our findings reveal that Alk is expressed in sympathetic
      and dorsal root ganglia as early as stage 19. In addition, mRNA is expressed from
      stage 23/24 (E4) to stage 39 (E13) in discrete motor neuron subsets of chick
      spinal cord along with a select group of muscles that are innervated by one of
      these particular motor neuron clusters. Expression within the spinal cord is
      coincident with the onset and duration of motor neuron programmed cell death and
      during the period of musculature innervation and synapse formation. Hence, the
      data presented here identify ALK as a novel candidate receptor for regulating
      critical events in the development of neurons in both the central and the
      peripheral nervous systems.

PMID- 16435288
TI  - CNS activational responses to staphylococcal enterotoxin B: T-lymphocyte
      dependent immune challenge effects on stress-related circuitry.
AB  - Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that engages the
      immune system in a T-lymphocyte-dependent manner and induces a cytokine profile
      distinct from that elicited by the better-studied bacterial pathogen analog,
      lipopolysaccharide (LPS). Because of reports of SEB recruiting central nervous
      system (CNS) host defense mechanisms via pathways in common with LPS, we sought
      to further characterize central systems impacted by this agent. Rats were treated
      with SEB at doses of 50-5,000 mug/kg, and killed 0.5-6 hours thereafter. SEB
      injection produced a discrete pattern of Fos induction in brain that peaked at 2
      3 hours postinjection and whose strength was dose-related. Induced Fos expression
      was predominantly subcortical and focused in a set of interconnected central
      autonomic structures, including aspects of the bed n. of the stria terminalis,
      central amygdala and lateral parabrachial nuclei; functionally related (and LPS
      responsive) cell groups in the n. solitary tract, ventrolateral medulla, and
      paraventricular hypothalamic n. (PVH) were, by contrast, weakly responsive. SEB
      also activated cell groups in the limbic forebrain (lateral septal n, medial
      prefrontal cortex) and hypothalamic GABAergic neurons, which could account for
      its failure to elicit reliable increases in Fos-ir or corticotropin-releasing
      factor (CRF) mRNA in the PVH. SEB nevertheless did provoke reliable pituitary
      adrenal secretory responses. The identification of subsets of central autonomic
      and limbic forebrain structures that are sensitive to SEB provides a basis for a
      systems-level understanding of the physiological and behavioral effects
      attributed to the superantigen. Core SEB-responsive cell groups exclude a
      medullary-PVH circuit implicated in pituitary-adrenal responses to LPS.

PMID- 16435289
TI  - Cytoarchitectonic subdivisions of the dorsolateral frontal cortex of the marmoset
      monkey (Callithrix jacchus), and their projections to dorsal visual areas.
AB  - We describe the organization of the dorsolateral frontal areas in marmoset
      monkeys using a combination of architectural methods (Nissl, cytochrome oxidase,
      and myelin stains) and injections of fluorescent tracers in extrastriate areas
      (the second visual area [V2], the dorsomedial and dorsoanterior areas [DM, DA],
      the middle temporal area and middle temporal crescent [MT, MTc], and the
      posterior parietal cortex [area 7]). Cytoarchitectural field 8 comprises three
      subdivisions: 8Av, 8Ad, and 8B. The ventrolateral subdivision, 8Av, forms the
      principal source of frontal projections to the "dorsal stream," having
      connections with each of the injected visual areas. The cytoarchitectural
      characteristics of 8Av suggest that this subdivision corresponds to the
      marmoset's frontal eye field. The intermediate subdivision of area 8 (8Ad) has
      efferent projections to area 7, while the dorsomedial subdivision (8B) has few or
      no connections with extrastriate cortex. Area 46, located rostrolateral to area
      8Av, has substantial connections with the medial extrastriate areas (DM, DA, and
      area 7) and with MT, while the cortex lateral to 8Av (area 12/45) projects
      primarily to MT and to the MTc. The rostromedial prefrontal (area 9) and
      frontopolar (area 10) regions have very few extrastriate projections. Finally,
      cells in dorsal area 6 (6d) have sparse projections to DM, MT, and the MTc, as
      well as strong projections to DA and to area 7. These results illuminate aspects
      of the evolutionary development of the primate frontal cortex, and serve as a
      basis for further research into cognitive functions using a marmoset model.

PMID- 16435290
TI  - GDNF/Ret signaling and the development of the kidney.
AB  - Signaling by GDNF through the Ret receptor is required for normal growth of the
      ureteric bud during kidney development. However, the precise role of GDNF/Ret
      signaling in renal branching morphogenesis and the specific responses of ureteric
      bud cells to GDNF remain unclear. Recent studies have provided new insight into
      these issues. The localized expression of GDNF by the metanephric mesenchyme,
      together with several types of negative regulation, is important to elicit and
      correctly position the initial budding event from the Wolffian duct. GDNF also
      promotes the continued branching of the ureteric bud. However, it does not
      provide the positional information required to specify the pattern of ureteric
      bud growth and branching, as its site of synthesis can be drastically altered
      with minimal effects on kidney development. Cells that lack Ret are unable to
      contribute to the tip of the ureteric bud, apparently because GDNF-driven
      proliferation is required for the formation and growth of this specialized
      epithelial domain.

PMID- 16435291
TI  - Trophoblast and hypoblast in the monotreme, marsupial and eutherian mammal:
      evolution and origins.
AB  - The pregastrula stage mammalian conceptus consists of both embryonic and non
      embryonic components. The latter forms the bulk of the tissues, provides
      nutrition for the developing embryo and also contributes developmental signals
      that influence events within the embryo itself. Understanding the origins and
      relationships between the embryonic and extraembryonic cell lineages is thus
      central to understanding development in mammals. Despite the apparent gross
      differences in early developmental strategy and form, the conceptuses of
      eutherian, marsupial and monotreme mammals show some remarkable similarities in
      the lineage allocation to trophoblast and hypoblast and in the emergent
      properties of the two cell types. We suggest that the gross differences can be
      explained by two relatively small evolutionary timing changes affecting cell
      adhesion patterns and the polarisation of developmentally significant
      information. These changes result in the conversion of a unilaminar blastocyst to
      a morula form composed of blastomeres with increased regulatory capacity.

PMID- 16435292
TI  - Scaffold proteins in MAP kinase signaling: more than simple passive activating
      platforms.
AB  - Due to the central position of scaffold proteins in numerous signaling networks,
      especially in MAPK pathways, considerable efforts have been made to identify new
      scaffolds and to characterize their function and regulation. Most of our
      knowledge stems from studies of yeast MAPK scaffolds, but the identification of
      such scaffolds in higher eukaryotes provided a new dimension to this field and
      led to exciting and promising new insights into the regulation of MAPK signaling.
      In this review, we shortly summarize the well-established basic functions of
      scaffolds in yeast and highlight concepts emerging from recent studies in yeast
      and higher eukaryotes. In particular, we discuss how scaffolds may actively
      influence MAPK signaling by inducing conformational changes of bound kinases or
      substrates, by controlling the localization of activated MAPK and the extent and
      output of MAPK activation, and by modulating MAPK kinetics through the
      recruitment of phosphatases or ubiquitin-ligases. Finally, we summarize the
      current knowledge of scaffold regulation, and how these events may be
      functionally important for MAPK signaling.

PMID- 16435293
TI  - Activation of the Nrf2-ARE signaling pathway: a promising strategy in cancer
      prevention.
AB  - A major protective mechanism against oxidizing substances capable of damaging DNA
      integrity and initiating carcinogenesis is the induction of phase II
      detoxification and antioxidant enzymes by chemopreventive agents. A key finding
      in the field of chemoprevention has been the discovery that the induction of
      these enzymes is mediated by the cytoplasmic oxidative stress system (Nrf2
      Keap1). Under basal (reducing) conditions, Keap1 anchors the Nrf2 transcription
      factor within the cytoplasm, targeting it for ubiquitination and proteasome
      degradation, thus repressing its ability to induce phase II genes. When cells are
      exposed to chemopreventive agents and oxidative stress, however, a signal
      involving phosphorylation and/or redox modification is transmitted to the Nrf2
      Keap1 complex, leading to its dissociation and the nuclear translocation of Nrf2,
      which, after hetero-dimerically partnering with other transcription factors,
      binds to the AREs/EpREs present within phase II gene promoters, increasing their
      transcription. These data should assist in developing new phase II detoxification
      enzyme inducers as cancer chemopreventive agents within the clinical environment.

PMID- 16435294
TI  - On the origin of telomeres: a glimpse at the pre-telomerase world.
AB  - Chromosomes may be either circular or linear, the latter being prone to erosion
      caused by incomplete replication, degradation and inappropriate repair. Despite
      these problems, the linear form of DNA is frequently found in viruses, bacteria,
      eukaryotic nuclei and organelles. The high incidence of linear chromosomes and/or
      genomes evokes why and how they emerged in evolution. Here we suggest that the
      primordial terminal structures (telomeres) of linear chromosomes in eukaryotic
      nuclei were derived from selfish element(s), which caused the linearization of
      ancestral circular genome. The telomeres were then essential in solving the
      emerged problems. Molecular fossils of such elements were recently identified in
      phylogenetically distant genomes and were shown to generate terminal arrays of
      tandem repeats. These arrays might mediate the formation of higher order
      structures at chromosomal termini that stabilize the linear chromosomal form by
      fulfilling essential telomeric functions.

PMID- 16435295
TI  - Ontologies for data and knowledge sharing in biology: plant ROS signaling as a
      case study.
AB  - Modern technologies have rapidly transformed biology into a data-intensive
      discipline. In addition to the enormous amounts of existing experimental data in
      the literature, every new study can produce a large amount of new data, resulting
      in novel ideas and more publications. In order to understand a biological process
      as completely as possible, scientists should be able to combine and analyze all
      such information. Not only molecular biology and bioinformatics, but all the
      other domains of biology including plant biology, require tools and technologies
      that enable experts to capture knowledge within distributed and heterogeneous
      sources of information. Ontologies have proven to be one of the most-useful means
      of constructing and formalizing expert knowledge. The key feature of an ontology
      is that it represents a computer-interpretable model of a particular subject
      area. This article outlines the importance of ontologies for systems biology,
      data integration and information analyses, as illustrated through the example of
      reactive oxygen species (ROS) signaling networks in plants.

PMID- 16435296
TI  - Development and phylogeny of arthropods.

PMID- 16435297
TI  - Getting from an RNA world to modern cells just got a little easier.
AB  - Our understanding of the early steps in the evolution of life is hampered by a
      Catch-22: Darwinian selection leading to longer genomes requires as prerequisite
      increased replicative fidelity. Yet a genome at capacity cannot increase in size;
      it will be catastrophically mutated out of existence if fidelity has not already
      increased. Traditionally the problem has been considered for genotypes but can be
      down-sized if multiple genotypes specify the same phenotype. Kun and colleagues
      put empirical meat on theoretical bone by analysing ribozyme mutagenesis data,
      concluding that modest replication fidelities could permit a primordial genome
      with up to 100 genes.

PMID- 16435298
TI  - Telomerase: not just for the elongation of telomeres.
AB  - Telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT)
      function together to elongate telomeres and to protect chromosomal ends. Recent
      studies have discovered that overexpression of telomerase's TERT subunit promoted
      epidermal stem-cell mobilization, hair growth and stem-cell proliferation without
      changes in length of telomeres.1,2 This telomerase functional characteristic is
      TERC independent and is operated through a mechanism other than telomere
      elongation. These findings open new doors for future explorations to understand
      telomerase function and its interaction with other cell components in the
      regulation of cell senescence and tumorigenesis.

PMID- 16435299
TI  - Magnetoreception.
AB  - The vector of the geomagnetic field provides animals with directional
      information, while intensity and/or inclination provide them with positional
      information. For magnetoreception, two hypotheses are currently discussed: one
      proposing magnetite-based mechanisms, the other suggesting radical pair processes
      involving photopigments. Behavioral studies indicate that birds use both
      mechanisms: they responded to a short, strong magnetic pulse designed to change
      the magnetization of magnetite particles, while, at the same time, their
      orientation was found to be light-dependent and could be disrupted by high
      frequency magnetic fields in the MHz range, which is diagnostic for radical pair
      processes. Details of these findings, together with electrophysiological and
      histological studies, suggest that, in birds, a radical pair mechanism located in
      the right eye provides directional information for a compass, while a magnetite
      based mechanism located in the upper beak records magnetic intensity, thus
      providing positional information. The mechanisms of magnetoreception in other
      animals have not yet been analyzed in detail.

PMID- 16435300
TI  - Notch and affinity boundaries in Drosophila.
AB  - Cells in multicellular organisms often do not intermingle freely with each other.
      Differential cell affinities can contribute to organizing cells into different
      tissues. Drosophila limbs and the vertebrate central nervous system are
      subdivided into compartments. Cells in adjacent compartments do not mix. Cell
      interactions mediated by Notch-family receptors have been implicated in the
      specification of these compartment boundaries. Two recent reports analyze the
      role of the Notch signaling pathway in the generation of an affinity boundary in
      the Drosophila wing. The first report analyzes the connection between Notch and
      the actin cytoskeleton. The second report analyzes the differential requirements
      of Notch and the transcription factor Suppressor of Hairless in generating the
      affinity boundary.

PMID- 16435301
TI  - Evolution of intraflagellar transport from coated vesicles and autogenous origin
      of the eukaryotic cilium.
AB  - The cilium/flagellum is a sensory-motile organelle ancestrally present in
      eukaryotic cells. For assembly cilia universally rely on intraflagellar transport
      (IFT), a specialised bidirectional transport process mediated by the ancestral
      and conserved IFT complex. Based on the homology of IFT complex proteins to
      components of coat protein I (COPI) and clathrin-coated vesicles, we propose that
      the non- vesicular, membrane-bound IFT evolved as a specialised form of coated
      vesicle transport from a protocoatomer complex. IFT thus shares common ancestry
      with all protocoatomer derivatives, including all vesicle coats and the nuclear
      pore complex (NPC). This has major implications for the evolutionary origin of
      the cilium. First, it reinforces the tenet that duplication and divergence of pre
      existing structures, rather than symbiosis, were the major themes during cilium
      evolution. Second, it suggests that the initial step in the autogenous origin of
      the cilium was the establishment of a membrane patch with transmembrane proteins
      transported by the ancestral vesicle-coating IFT complex. We propose a scenario
      for how the initial membrane patch gradually protruded to enhance exposure to the
      environment, then started to move, and finally compartmentalised to render
      receptor signalling and ciliary beating more efficient.

PMID- 16435302
TI  - The dual role of Fas-ligand as an injury effector and defense strategy in
      diabetes and islet transplantation.
AB  - The exact process that leads to the eruption of autoimmune reactions against beta
      cells and the evolution of diabetes is not fully understood. Macrophages and T
      cells may launch an initial immune reaction against the pancreatic islets of
      Langerhans, provoking inflammation and destructive insulitis. The information on
      the molecular mechanisms of the emergence of beta cell injury is controversial
      and points to possibly important roles for the perforin-granzyme, Fas-Fas-ligand
      (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several
      unique features that make it a potentially ideal immunomodulatory tool. Most
      important, FasL is selectively toxic to cytotoxic T cells and less harmful to
      regulatory T cells. This review discusses the intrinsic sensitivity of beta cells
      to FasL-mediated apoptosis, the conditions that underlie this beta cell
      sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent
      islet allograft rejection. In both the autoimmune and transplant settings, it is
      imperative to progress from the administration of nonspecific immunosuppressive
      therapy to the concept of beta-cell-specific immunomodulation. FasL evolves as a
      prime candidate for antigen-specific immunomodulation.

PMID- 16435303
TI  - Correcting an error. Re: Dr. Harris's response to: Soto AM, Sonnenschein C. 2004.
      The somatic mutation theory of cancer: growing problems with the paradigm?
      BioEssays 26: 1097-1107.

PMID- 16435304
TI  - Elements for an integrated approach to carcinogenesis.

PMID- 16435305
TI  - Spatiotemporal distribution of Connexin45 in the olivocerebellar system.
AB  - The olivocerebellar system is involved in the transmission of information to
      maintain sensory motor coordination. Gap junctions have been described in various
      types of neurons in this system, including the neurons in the inferior olive that
      provide the climbing fibers to Purkinje cells. While it is well established that
      Connexin36 is necessary for the formation of these neuronal gap junctions, it is
      not clear whether these electrical synapses can develop without Connexin45. Here
      we describe the development and spatiotemporal distribution of Connexin45 in
      relation to that of Connexin36 in the olivocerebellar system. During development
      Connexin45 is expressed in virtually all neurons of the inferior olive and
      cerebellar nuclei. During later postnatal development and adulthood there is a
      considerable overlap of expression of both connexins in subpopulations of all
      main olivary nuclei and cerebellar nuclei as well as in the stellate cells in the
      cerebellar cortex. Despite this prominent expression of Connexin45,
      ultrastructural analysis of neuronal gap junctions in null-mutants of Connexin45
      showed that their formation appears normal in contrast to that in knockouts of
      Connexin36. These morphological data suggest that Connexin45 may play a modifying
      role in widely distributed, coupled neurons of the olivocerebellar system, but
      that it is not essential for the creation of its neuronal gap junctions.

PMID- 16435307
TI  - Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic
      ectodermal dysplasia.
AB  - Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development
      of the eccrine sweat glands, hair, and teeth. The X-linked form of the disease,
      caused by mutations in the ED1 gene, represents the majority of HED cases.
      Autosomal-dominant and -recessive forms occur occasionally and result from
      mutations in at least two genes: EDAR and EDARADD. These different forms are
      phenotypically indistinguishable. To better assess the implication of the EDAR
      gene in HED, we screened for mutations in 37 unrelated HED families or sporadic
      cases with no detected mutations in the ED1 gene. We identified 11 different
      mutations, nine of which are novel variants, in two familial and seven sporadic
      cases. Seven of the 11 are recessive mutations (c.140G>A (p.Cys47Tyr), c.266G>A
      (p.Arg89His), c.329A>C (p.Asp110Ala), c.442T>C (p.Cys148Arg), c.1208C>T
      (p.Thr403Met), c.1302G>T (p.Trp434Cys) and c.528+1G>A), and the other four are
      probably dominant (c.1129C>T (p.Leu377Phe), c.1237A>C (p.Thr413Pro), c.1253T>C
      (p.Ile418Thr), and c.1259G>A (p.Arg420Gln)). Our study demonstrates that EDAR is
      implicated in about 25% of non-ED1 HED, and may account for both autosomal
      dominant and -recessive forms. The correlation between the nature and location of
      EDAR mutations and their mode of inheritance is discussed. A genotype-phenotype
      relationship was evaluated, since such data could be helpful for genetic
      counseling.

PMID- 16435308
TI  - Parallelization of the deMon2k code.
AB  - The parallelization of the LCGTO-KS-DFT code deMon2k is presented. The
      parallelization of the three-center electron repulsion integrals, the numerical
      integration using a direct grid algorithm and the matrix multiplication and
      diagonalization are described. The efficiency of the parallelization is analyzed
      by selected benchmark calculations. It is shown that geometry optimizations of
      systems with more than 8,000 basis functions are feasible on cluster
      architectures.

PMID- 16435309
TI  - A functional hypothesis for adult hippocampal neurogenesis: avoidance of
      catastrophic interference in the dentate gyrus.
AB  - The dentate gyrus is part of the hippocampal memory system and special in that it
      generates new neurons throughout life. Here we discuss the question of what the
      functional role of these new neurons might be. Our hypothesis is that they help
      the dentate gyrus to avoid the problem of catastrophic interference when adapting
      to new environments. We assume that old neurons are rather stable and preserve an
      optimal encoding learned for known environments while new neurons are plastic to
      adapt to those features that are qualitatively new in a new environment. A simple
      network simulation demonstrates that adding new plastic neurons is indeed a
      successful strategy for adaptation without catastrophic interference.

PMID- 16435310
TI  - Prolonged seizures recruit caudal subventricular zone glial progenitors into the
      injured hippocampus.
AB  - Neurogenesis persists in the adult rat rostral forebrain subventricular zone
      (SVZ) and is stimulated by status epilepticus (SE). More caudal SVZ (cSVZ) neural
      progenitors migrate to the hippocampus after ischemic injury and contribute to
      CA1 pyramidal cell regeneration. Because SE also damages the hippocampus, we
      examined the effects of SE on cSVZ precursors. SE was induced in adult rats with
      pilocarpine, and cell proliferation in cSVZ and hippocampus was examined by
      bromodeoxyuridine (BrdU) and retroviral reporter labeling. Neural precursors were
      assayed by immunostaining for specfic markers between 1 and 35 days after SE.
      BrdU-positive cells labeled prior to SE markedly increased in numbers within 1-2
      weeks in the cSVZ and infracallosal region, but not in the corpus callosum.
      Doublecortin-, polysialic acid neural cell adhesion molecule-, and TUC-4
      (TOAD/Ulip/CRMP family-4)-immunostained cells with migrating morphology increased
      with a similar time course after SE and extended from the cSVZ to CA1 and CA3
      regions. Retroviral reporters injected into the cSVZ of controls showed labeled
      cells with oligodendroglial morphology located in the cSVZ and corpus callosum;
      when injected 2 days prior to SE, many more reporter-labeled cells appeared
      several weeks later and were located in the cSVZ, corpus callosum, and
      hippocampus. Labeled cells showed glial morphologies and expressed astrocyte or
      oligodendrocyte markers. Neither BrdU- nor retroviral reporter-labeled cells
      coexpressed neuronal markers in controls or pilocarpine-treated rats. These
      results indicate that SE increases cSVZ gliogenesis and attracts newly generated
      glia to regions of hippocampal damage. Further study of seizure-induced
      gliogenesis may provide insight into mechanisms of adult neural progenitor
      regulation and epileptogenesis.

PMID- 16435311
TI  - Irradiation as an experimental tool in studies of adult neurogenesis.
AB  - "Loss of function" experiments have been the mainstay approach in studies seeking
      to determine functional roles of various brain regions in learning and memory.
      The hippocampal formation consists of several distinct regions that are thought
      to play different, yet interrelated, roles in the memory processes. Ionizing
      radiation offers a selective and highly flexible, relatively uninvasive method to
      further advance such studies. Focused applications of the radiation beam to the
      head under general anesthesia can selectively reduce ongoing adult neurogenesis
      in the dentate gyrus without causing any detectable damage to mature neurons.
      Further refinements of the methodology should offer many opportunities to extend
      our present knowledge of how and when adult neurogenesis plays a role in learning
      and memory.

PMID- 16435312
TI  - Why women want prenatal ultrasound in normal pregnancy.
AB  - OBJECTIVES: To investigate women's reasons for requesting prenatal ultrasound in
      the absence of clinical indications. METHODS: A postal questionnaire was
      completed by 370 pregnant women with no apparent obstetric risk factors, who had
      expressed a desire to have ultrasound scanning in their current pregnancy. The
      women were asked to indicate, from a list of 12 items, their three most important
      reasons for wanting scanning. Ninety per cent of the women were in the first
      trimester of pregnancy, and 10% in the second trimester. RESULTS: The items most
      frequently identified as important reasons for ultrasound were to check for fetal
      abnormalities (60% of women), to see that all was normal (55%) and for own
      reassurance (44%). Lower income was related to wanting to see the baby (P =
      0.028) and wanting an ultrasound picture (P = 0.017); higher income was related
      to checking that all was normal (P = 0.003) and for own reassurance (P = 0.015).
      Women in their first pregnancy were more likely to want themselves and the father
      to see the baby (P = 0.001); women who had given birth previously were more
      likely to want reassurance (P = 0.002), as were women with a previous miscarriage
      or induced abortion. Women who believed that the presence of fetal trisomy
      justifies abortion or who would vote for free abortion were more likely to want
      to know about abnormalities (P < 0.001 and P < 0.004, respectively). Women in the
      second trimester were more likely to want to check for abnormalities (P = 0.041)
      and appropriate fetal growth (P = 0.047) than those in the first trimester.
      CONCLUSIONS: It would appear that women in normal pregnancy have specific reasons
      for wanting prenatal ultrasound that are influenced by sociodemographic,
      obstetric and attitudinal factors.

PMID- 16435313
TI  - Early onset of subclinical atherosclerosis in women with gestational diabetes
      mellitus.
AB  - OBJECTIVE: Common carotid artery intima-media thickness (CIMT) is a non
      invasively assessed marker of subclinical atherosclerosis. Our aim in this study
      was to investigate CIMT in women with gestational diabetes mellitus (GDM).
      METHODS: Thirty women with GDM and 40 unaffected women (as a control group) were
      included in the study. Blood samples were drawn from each woman in the morning
      after they had fasted for at least 8 h, and levels of fasting glucose, insulin,
      homocysteine, total cholesterol, high-density lipoprotein (HDL) cholesterol,
      triglycerides, low-density lipoprotein (LDL) cholesterol and very low-density
      lipoprotein (VLDL) cholesterol were measured, along with the CIMT in the two
      groups. RESULTS: The mean triglyceride (P = 0.016) and VLDL cholesterol (P =
      0.011) levels in the GDM group were significantly higher than those in the
      unaffected women. There were no significant differences between the groups with
      respect to plasma levels of total cholesterol, HDL cholesterol, LDL cholesterol
      and insulin. The mean homocysteine (P = 0.027) and fasting glucose (P = 0.019)
      levels in women with GDM were significantly higher than those in the control
      group. Patients with GDM had significantly higher CIMT than did the unaffected
      women (0.582 +/- 0.066 mm vs. 0.543 +/- 0.049 mm, P = 0.006). CIMT correlated
      positively with maternal age (r = 0.316, P = 0.008), body mass index (BMI) at the
      time of a 50-g oral glucose load test (r = 0.414, P = 0.001) and homocysteine
      levels (r = 0.332, P = 0.008), and fasting glucose (r = 0.265, P = 0.031) and 1-h
      glucose value (r = 0.410, P = 0.001) at the time of the oral glucose tolerance
      test. There was a positive correlation between the presence of GDM and CIMT (r =
      0.372, P = 0.001). However, stepwise multiple regression analysis showed that
      GDM/no GDM (95% CI +0.012 to +0.076, P = 0.008) and BMI at the time of the 50-g
      test (95% CI +0.001 to +0.009, P = 0.011) were independent parameters related to
      CIMT. CONCLUSION: Women with GDM have increased CIMT compared with unaffected
      women.

PMID- 16435314
TI  - GABAergic signaling in young granule cells in the adult rat and mouse dentate
      gyrus.
AB  - Throughout most of the developing brain, including the hippocampus, GABAergic
      synapses are the first to become functional. Several features of GABAergic
      signaling change across development, suggesting that this signaling in the
      immature brain may play important roles in the growth of young neurons and the
      establishment of networks. To determine whether GABA(A) receptor (GABA(A)R)
      containing synapses in new neurons born in the adult dentate gyrus have similar
      immature features, we examined spontaneous and evoked GABA(A)R-mediated synaptic
      currents in young (POMC-EGFP or doublecortin-immunostained) granule cells in
      acute slice preparations from adult mice and rats. Spontaneous inhibitory
      postsynaptic currents (IPSCs) were observed in nearly all immature granule cells,
      but their frequency was considerably lower and their decay time constant was
      nearly two times longer than in neighboring mature (doublecortin-non
      immunoreactive or EGFP-non-expressing) granule cells within the sub-granular
      zone. Evoked IPSCs (eIPSCs) in mature granule cells, but not immature granule
      cells, were sensitive to zolpidem, suggesting a maturational increase in GABA(A)R
      alpha1-subunit expression. Perforated-patch recording revealed that eIPSCs
      depolarized young neurons, but hyperpolarized mature neurons. The early
      establishment of synaptic GABAergic inputs slow IPSC decay time, and depolarizing
      action of eIPSCs are remarkably similar to features previously seen in neurons
      during development, suggesting that they are intrinsic features of immature
      neurons and not functions of the surrounding circuitry. These developmental
      features in adult-born granule cells could play a role in maturational processes
      such as developmental cell death. However, treatment of adult mice with GABA(A)R
      agonists and an inverse agonist did not significantly alter the number of 4- to
      14-day-old BrdU-labeled cells.

PMID- 16435315
TI  - Interneurons targeting similar layers receive synaptic inputs with similar
      kinetics.
AB  - GABAergic interneurons play diverse and important roles in controlling neuronal
      network dynamics. They are characterized by an extreme heterogeneity
      morphologically, neurochemically, and physiologically, but a functionally
      relevant classification is still lacking. Present taxonomy is essentially based
      on their postsynaptic targets, but a physiological counterpart to this
      classification has not yet been determined. Using a quantitative analysis based
      on multidimensional clustering of morphological and physiological variables, we
      now demonstrate a strong correlation between the kinetics of glutamate and GABA
      miniature synaptic currents received by CA1 hippocampal interneurons and the
      laminar distribution of their axons: neurons that project to the same layer(s)
      receive synaptic inputs with similar kinetics distributions. In contrast, the
      kinetics distributions of GABAergic and glutamatergic synaptic events received by
      a given interneuron do not depend upon its somatic location or dendritic
      arborization. Although the mechanisms responsible for this unexpected observation
      are still unclear, our results suggest that interneurons may be programmed to
      receive synaptic currents with specific temporal dynamics depending on their
      targets and the local networks in which they operate.

PMID- 16435316
TI  - Development of the tentacular apparatus in sipunculans (Sipuncula): I.
      Thysanocardia nigra (Ikeda, 1904) and Themiste pyroides (Chamberlin, 1920).
AB  - The development and arrangement of the tentacular apparatus of Thysanocardia
      nigra (Ikeda, 1904) and Themiste pyroides (Chamberlin, 1920) are described and
      illustrated using scanning electron microscopy. In T. nigra, the tentacular
      apparatus is composed of two crowns: the nuchal arc enclosing the nuchal organ
      and a crown of numerous oral tentacles arranged in U-shaped festoons. In early
      juveniles, two dorsal horn-like protrusions develop into the first, or primary,
      pair of tentacles of the nuchal arc. The second pair of tentacles of the nuchal
      arc develops dorsolaterally on the bases of the primary tentacles. Two
      ventrolateral lobes of the oral disk grow and become subdivided by the
      longitudinal ciliary groove into anlages of one set of dorsal and one set of
      ventral tentacles, thus forming a first oral festoon. Later, a pair of
      dorsolateral lobes develop between the first festoons and the nuchal arc to form
      a second pair of oral festoons. The third and following pairs of oral festoons
      develop in the dorsolateral growth zones lateral to the borders of the nuchal
      arc, where they meet the oral crown. The growing festoons extend down the oral
      disk and run alongside the head. A new oral tentacle appears directly at/on the
      base of the previous tentacle, thus giving rise to a typical sympodium with an
      alternating arrangement of tentacles. In T. pyroides, a second pair of tentacles
      develops from two ciliary lobes that are ventrolateral outgrowths of the
      circumoral ciliary field around the terminal mouth opening. The third pair of
      tentacles appears from the dorsolateral lobes at the base of primary tentacles,
      between the first two pairs of tentacles. These six tentacles determine the
      position of six main stems of the tentacular apparatus designated the first
      tentacles in the corresponding stems. The second tentacle in every stem appears
      as a ventrolateral outgrowth at the base of the first tentacle. The third and
      following tentacles in the stem are developed between the two previous tentacles
      according to a sympodial pattern. In both species, the distinct sympodial pattern
      in the arrangement of tentacles in the tentacular apparatus is well evidenced by
      the outlines of the ciliary oral grooves. The branched stems of T. pyroides may
      be homologized structurally and functionally to the oral festoons of T. nigra. J.
      Morphol. (c) 2006 Wiley-Liss, Inc.

PMID- 16435317
TI  - First-trimester maternal serum levels of placental hormones are independent
      predictors of second-trimester fetal growth parameters.
AB  - OBJECTIVE: To determine whether first-trimester maternal serum levels of
      pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic
      gonadotropin (fbeta-hCG) are independent predictors of second-trimester fetal
      growth parameters. METHODS: This was a cohort study over a 1-year period
      involving 594 Chinese women who underwent both first-trimester combined screening
      for Down syndrome and a routine second-trimester ultrasound examination. Maternal
      PAPP-A and fbeta-hCG levels (expressed in log(10) of multiples of median (MoM)),
      crown-rump length (CRL) (expressed in standardized Z-score (Z-CRL)), and maternal
      height and weight, were correlated with the Z-score of biparietal diameter (Z
      BPD), femur length (Z-FL) and abdominal circumference (Z-AC) measured in the
      second trimester, using the Pearson test, followed by multiple regression
      analysis. RESULTS: Z-BPD, Z-FL and Z-AC were positively correlated with log(10)
      PAPP-A MoM, CRL and maternal height (all P < 0.05), while log(10) fbeta-hCG MoM
      was negatively correlated with Z-AC (P < 0.05). After controlling for the effects
      of CRL, maternal height and weight, log(10) PAPP-A MoM was found to be an
      independent positive predictor of Z-FL (r = 0.797, P < 0.001) and Z-AC (r =
      0.305, P = 0.049), and log(10) fbeta-hCG MoM was an independent negative
      predictor of Z-FL (r = -0.381, P = 0.023) and Z-AC (r = -0.418, P = 0.002).
      Neither hormonal level was related to Z-BPD. CONCLUSIONS: First-trimester PAPP-A
      and fbeta-hCG are independent factors that influence subsequent fetal growth.
      PAPP-A level is positively correlated with FL and AC in the second trimester,
      while fbeta-hCG level is negatively correlated with them. However, BPD is not
      affected by either of the hormones.

PMID- 16435318
TI  - Strain rate derived from color Doppler myocardial imaging for assessment of fetal
      cardiac function.
AB  - OBJECTIVE: Color Doppler myocardial imaging (CDMI) is a new multigated method
      that allows direct analysis of myocardial motion. It is superior to pulsed-wave
      tissue Doppler in its ability to generate new and important indices of myocardial
      function such as strain, strain rate and tissue tracking. The purpose of this
      study was to assess the feasibility of CDMI in the fetal heart. METHODS: Three
      normal fetuses of gestational ages 20 + 1, 28 + 1 and 36 + 0 weeks and a fetus of
      20 + 3 weeks with aortic valve atresia were studied. Velocity data were acquired
      from the apical four-chamber view using a Vivid 7 ultrasound platform with
      integrated software for CDMI and with frame rates around 200/s. Data were post
      processed using dedicated software and with the sample area placed at the
      subvalvular and middle part of the septum and the ventricular walls. RESULTS:
      CDMI was feasible in all fetuses. The fetus with aortic valve atresia had
      severely reduced strain rate of the left ventricular wall. CONCLUSIONS: Using
      this new technique it is possible to obtain information on the global and
      regional contractility of the fetal heart and thereby gain new insights into the
      physiology of the fetal cardiovascular system. CDMI is a promising new method for
      monitoring at-risk fetuses.

PMID- 16435319
TI  - Prenatal diagnosis of an isolated aneurysm of the ascending aorta.

PMID- 16435320
TI  - Prenatal diagnosis and therapy of upper extremity vascular malformation causing
      high cardiac output and Kasabach-Merritt sequence: a report of two cases.
AB  - We present two cases of upper extremity vascular malformation causing a high
      output state in the prenatal period. One fetus responded well to transplacental
      digitalis treatment. Both newborns had a Kasabach-Meritt sequence including
      anemia and thrombocytopenia. Postpartum treatment included successful
      interventional occlusion of the main feeding arteries and subsequent surgical
      removal of the tumor.

PMID- 16435321
TI  - The detection rate for lung metastases or synchronous lung primary tumors in
      patients with newly diagnosed head and neck squamous cell carcinoma.

PMID- 16435322
TI  - Three-dimensional transperineal ultrasonography for evaluation of the anal
      sphincter complex: another dimension in understanding peripartum sphincter
      trauma.

PMID- 16435323
TI  - Prenatal detection and evaluation of an extralobar pulmonary sequestration in the
      posterior mediastinum.
AB  - Extralobar pulmonary sequestration (EPS) is a rare developmental anomaly with
      aberrant nonfunctioning parenchymal tissue, associated with an increased risk of
      perinatal morbidity and, rarely, mortality owing to possible neonatal respiratory
      distress. In most cases supernumerary lobes are detected as isolated intra- or
      extrapleural lesions with independent systemic arterial blood supply. We report
      an atypical case of prenatal detection and perinatal outcome of a mediastinal
      EPS.

PMID- 16435324
TI  - Health-promoting physical activity of adults with mental retardation.
AB  - This literature review describes the physical activity behavior of adults with
      mental retardation consistent with the U.S. Surgeon General's recommendation of
      30 minutes of moderate intensity physical activity on 5 or more days per week.
      The proportion of participants achieving this criterion ranges from 17.5 to 33%.
      These data are likely to be generous estimates of activity as individuals
      included in physical activity studies to date have been relatively young and
      healthy volunteers with mild to moderate limitations. Major sources of physical
      activity were walking and cycling for transport, chores and work, dancing, and
      Special Olympics. There is a pressing need to conduct studies using appropriately
      powered representative samples and to validate measures that assess physical
      activity less directly; including methodologies in which proxy respondents are
      used. Accurate information about existing patterns of behavior will enhance the
      development of effective strategies to promote physical activity among persons
      with mental retardation.

PMID- 16435325
TI  - Vision and oral health needs of individuals with intellectual disability.
AB  - Over the past 20 years, there has been an increased emphasis on health promotion,
      including prevention activities related to vision and oral health, for the
      general population, but not for individuals with intellectual disability (ID).
      This review explores what is known about the prevalence of vision problems and
      oral health conditions among individuals with ID, presents a rationale for the
      increased prevalence of these conditions in the context of service utilization,
      and examines the limitations of the available research. Available data reveal a
      wide range of prevalence estimates for vision problems and oral health
      conditions, but all suggest that these conditions are more prevalent among
      individuals with ID compared with the general population, and disparities exist
      in the receipt of preventive and early treatment for these conditions for
      individuals with ID. Recommendations for health improvement in these areas
      include better health planning and monitoring through standardized population
      based data collection and reporting and increased emphasis on health promotion
      activities and early treatment in the healthcare system.

PMID- 16435326
TI  - A review of substance use research among those with mental retardation.
AB  - This article reviews research conducted on the cigarette, alcohol, and illicit
      drug use of adolescents and adults with mental retardation (MR). The majority of
      the research related to substance use conducted on this population has been
      limited to surveys. Overall, results of these studies suggest that, although
      substance use is slightly lower among those with MR than among nondisabled
      comparison groups, it is nonetheless a problem for many individuals. This
      research is reviewed and a discussion of both the general and specific flaws of
      these studies follows. Further, the examination of education, prevention, and
      treatment programs for this population has been overlooked, indicating that
      individuals with MR are likely not receiving the services most appropriate for
      them. The article concludes with a discussion of several topics that need to be
      addressed in future studies, including research on potential best practices in
      the overlooked areas of substance abuse interventions.

PMID- 16435327
TI  - A cascade of disparities: health and health care access for people with
      intellectual disabilities.
AB  - People with ID represent approximately 2% of the population and, as a group,
      experience poorer health than the general population. This article presents
      recent conceptualizations that begin to disentangle health from disability,
      summarizes the literature from 1999 to 2005 in terms of the cascade of
      disparities, reviews intervention issues and promising practices, and provides
      recommendations for future action and research. The reconceptualization of health
      and disability examines health disparity in terms of the determinants of health
      (genetic, social circumstances, environment, individual behaviors, health care
      access) and types of health conditions (associated, comorbid, secondary). The
      literature is summarized in terms of a cascade of disparities experienced by
      people with ID, including a higher prevalence of adverse conditions, inadequate
      attention to care needs, inadequate focus on health promotion, and inadequate
      access to quality health care services. Promising practices are reviewed from the
      perspective of persons with ID, providers of care and services, and policies that
      influence systems of care. Recommendations across multiple countries and
      organizations are synthesized as guidelines to direct future action. They call
      for promoting principles of early identification, inclusion, and self
      determination of people with ID; reducing the occurrence and impact of
      associated, comorbid, and secondary conditions; empowering caregivers and family
      members; promoting healthy behaviors in people with ID; and ensuring equitable
      access to quality health care by people with ID. Their broadscale implementations
      would begin to reduce the health disparity experienced by people with ID.

PMID- 16435328
TI  - Cardiovascular disease prevalence and risk factors of persons with mental
      retardation.
AB  - This paper reviews the recent literature on cardiovascular disease (CVD)
      prevalence, CVD-related mortality, physiological CVD risk factors, and behavioral
      CVD risk factors in adults with mental retardation (MR). The literature on the
      potential influences of modifiable behavioral CVD risk factors and the
      physiological CVD risk factors are also reviewed. Adults with mild to moderate MR
      residing in community settings appear to have an elevated disease prevalence,
      elevated CVD-related mortality, more adverse physiological CVD risk factors, and
      elevated behavioral risk compared to others with and without MR. Preliminary
      evidence supports the benefits of participating in the recommended physical
      activity levels and consuming the recommended diets to reduce the risk for CVD.
      The lack of large-scale longitudinal or experimental research indicates a gap in
      the research. The development of research-based, appropriate, primary prevention
      programs and intervention strategies aimed at lowering the risk for CVD is highly
      recommended. Programs should focus on educating individuals with MR along with
      direct care providers and family members on the importance of appropriate dietary
      concepts, physical activity habits, and regular health screenings by physicians.
      Programs should be individualized to regional and cultural issues.

PMID- 16435329
TI  - Obesity and intellectual disability.
AB  - While much of the industrialized world struggles for clues to the growing rise in
      obesity in their respective countries, researchers and service providers involved
      in understanding the health characteristics and health behaviors of persons with
      intellectual disability (ID) struggle with their own issues regarding the
      increased prevalence of obesity in this segment of the population. What is
      particularly alarming is that adults with ID residing in the United States in
      smaller, less supervised settings (e.g., group homes and family households) have
      a significantly higher rate of obesity compared to other countries and those
      living in larger and more supervised settings (e.g., institutions). These
      differences support the theory that the environment appears to exert a powerful
      influence on obesity in this population. Obesity presents a substantial threat to
      the livelihood of persons with ID and may have an effect on community
      participation, independent living, and healthy years of life. The lack of
      research on successful weight reduction strategies for obese persons with ID
      makes this an important and greatly needed area of research.

PMID- 16435330
TI  - Sexual health care in persons with intellectual disabilities.
AB  - In the past, preventive health concerning sexuality of people with intellectual
      disabilities was addressed through surgical sterilization as part of nationwide
      eugenic programs in many countries. For more than 30 years now, it has come
      progressively to light in the scientific literature that, besides major ethical
      and legal problems, these programs also failed to assess many of the individual's
      needs in sexual health. The fact that an increasing number of people with
      intellectual disabilities live in the community rather than in institutions has
      heightened public awareness that these individuals have sexual expectancies,
      desires, and needs that must be supported through both education and health
      services. The emergence of AIDS, including descriptions of cases among people
      with intellectual disabilities, has further demonstrated that surgical
      sterilization cannot be considered a global option to achieve preventive sexual
      health. The aim of this paper is to review scientific studies that have assessed
      the expectancies and support needs of persons with intellectual disabilities in
      terms of sexual health. These needs vary widely from one individual to another,
      according to life milieu, level of disability, and potential comorbidity. From
      this review, it appears that hygiene management, global gynecological care, and
      prevention of unplanned pregnancy, sexually transmitted diseases, and abuse have
      been frequently identified as areas in which the presence of intellectual
      disability dictates specific support needs. Different approaches that have been
      evaluated to address these issues will also be discussed.

PMID- 16435331
TI  - Prevalence of maltreatment of people with intellectual disabilities: a review of
      recently published research.
AB  - Maltreatment can have a profound adverse effect on the health of individuals with
      intellectual disabilities (ID). People with ID may also be more likely to
      experience maltreatment than other groups. Historically, data on prevalence of
      maltreatment among people with ID have been sparse and methodologically weak but
      have suggested that the scope of the problem is considerable. Studies published
      between 1995 and 2005 were reviewed to determine estimated maltreatment
      prevalence among people with ID based on recent literature. Prevalence estimates
      for people with ID were compared to estimates for people with no disabilities and
      people with other types of disabilities. Only five studies provided maltreatment
      prevalence estimates for people with ID. The limited data suggest that
      maltreatment is more prevalent for people with ID than for people with no
      disabilities and may be higher for people with ID than for people with certain
      other disabilities. Most of the available research is still based on convenience
      samples. More population-level data are needed to provide reliable estimates of
      the prevalence of this important health problem.

PMID- 16435332
TI  - Introduction: preventive health and individuals with mental retardation.

PMID- 16435333
TI  - Facial cleft or shadowing artifact?

PMID- 16435334
TI  - An elliptic spatial scan statistic.
AB  - The spatial scan statistic is commonly used for geographical disease cluster
      detection, cluster evaluation and disease surveillance. The most commonly used
      shape of the scanning window is circular. In this paper we explore an elliptic
      version of the spatial scan statistic, using a scanning window of variable
      location, shape (eccentricity), angle and size, and with and without an
      eccentricity penalty. The method is applied to breast cancer mortality data from
      Northeastern United States and female oral cancer mortality in the United States.
      Power comparisons are made with the circular scan statistic.

PMID- 16435335
TI  - Fetal lung volumetry: a step closer to a clinically acceptable predictor of lung
      hypoplasia?

PMID- 16435336
TI  - Diagnostic difficulties of pelvic splenosis: case report.
AB  - We report the case of a 38-year-old woman who presented with chronic lower
      abdominal pain. Her past medical history included a splenectomy due to abdominal
      trauma. Ultrasound examination revealed four pelvic tumors which, upon
      laparotomy, were found to be the result of splenosis. Approximately 100 cases of
      splenosis have been reported but only a minority of them have been published in
      the gynecological literature. Our case indicates that those involved in pelvic
      scanning (even of asymptomatic women) and/or treating those complaining of lower
      abdominal pain or presenting with pelvic tumors should be aware of splenosis as a
      possible diagnosis.

PMID- 16435337
TI  - Multiple imputation for correcting verification bias.
AB  - In the case in which all subjects are screened using a common test and only a
      subset of these subjects are tested using a golden standard test, it is well
      documented that there is a risk for bias, called verification bias. When the test
      has only two levels (e.g. positive and negative) and we are trying to estimate
      the sensitivity and specificity of the test, we are actually constructing a
      confidence interval for a binomial proportion. Since it is well documented that
      this estimation is not trivial even with complete data, we adopt multiple
      imputation framework for verification bias problem. We propose several imputation
      procedures for this problem and compare different methods of estimation. We show
      that our imputation methods are better than the existing methods with regard to
      nominal coverage and confidence interval length.

PMID- 16435338
TI  - A pattern-mixture model for the analysis of censored quality-of-life data.
AB  - We propose a pattern-mixture model for describing the joint distribution of
      incomplete repeated measurements of quality of life (QoL) and right-censored
      survival times. The model assumes that the survival times follow a multinomial
      distribution and that the quality of life outcome follows a multivariate normal
      distribution conditional on the survival time. We estimate the model using a
      Bayesian approach by importance sampling. We then use simulated parameters to
      create multiple imputations of the censored QoL outcomes, which can then be used
      to calculate individual values of quality-adjusted life-years (QALYs). We apply
      the method to data from the Randomized Evaluation of Mechanical Assistance in the
      Treatment of Congestive Heart Failure (REMATCH) clinical trial.

PMID- 16435339
TI  - Modelling competing risks in cancer studies.
AB  - Competing risks arise commonly in the analysis of cancer studies. Most common are
      the competing risks of relapse and death in remission. These two risks are the
      primary reason that patients fail treatment. In most medical papers the effects
      of covariates on the three outcomes (relapse, death in remission and treatment
      failure) are model by distinct proportional hazards regression models. Since the
      hazards of relapse and death in remission must add to that of treatment failure,
      we argue that this model leads to internal inconsistencies. We argue that
      additive models for either the hazard rates or the cumulative incidence functions
      are more natural and that these models properly partition the effect of a
      covariate on treatment failure into its component parts. We illustrate the use
      and interpretation of additive models for the hazard rate or for the cumulative
      incidence function using data from a study of the efficacy of two preparative
      regimes for hematopoietic stem cell transplantation.

PMID- 16435340
TI  - Multilocus linkage disequilibrium mapping of epistatic quantitative trait loci
      that regulate HIV dynamics: a simulation approach.
AB  - The time-dependent change of HIV particle load, i.e. HIV dynamics, is likely to
      be controlled by a multitude of quantitative trait loci (QTL) that interact with
      each other as well as with various developmental and environmental factors in a
      coordinated manner. In this article, we have derived a new statistical model for
      mapping the epistatic QTL responsible for HIV dynamics in a natural human
      population. This model, constructed on the integrated theme of functional mapping
      and linkage disequilibrium (LD) mapping, can make use of information from
      multiple markers genotyped from the human genome. It allows for the test and
      estimation of genetic actions and interactions involved in the control of HIV
      progression and provides a general platform to identify the detailed genetic
      architecture of resistance or susceptibility of humans to HIV on a dynamic scale.
      We have generalized this model to accommodate various complicated clincal designs
      for AIDS studies. Simulation studies with different scenarios are performed to
      examine the statistical behaviour of the model. The genetic and statistical
      extensions of this mapping model to HIV/AIDS genomic research are discussed.

PMID- 16435341
TI  - Mechanomyographic and electromyographic responses to eccentric muscle
      contractions.
AB  - Little is known regarding the modulation of torque during eccentric muscle
      actions. Mechanomyographic (MMG) and electromyographic (EMG) signals have been
      used to examine motor control strategies. The purpose of this study was to
      examine the MMG and EMG amplitude and frequency in relation to torque during
      eccentric muscle contractions. Eight women performed eccentric leg extension
      muscle contractions at 10-100% of peak torque (PT). A piezoelectric crystal
      contact sensor and bipolar surface electrodes were placed on the vastus medialis
      to detect the MMG and EMG signals. Polynomial regression analyses indicated that
      EMG amplitude (r(2)=0.994) and MMG wavelet center frequency (CF) (r(2)=0.846)
      increased linearly to 100% eccentric PT, whereas there were no significant
      relationships for EMG wavelet CF or MMG amplitude and eccentric torque. These
      results suggested that eccentric torque is primarily modulated through changes in
      motor unit firing rate.

PMID- 16435342
TI  - Augmentation of the contraction force of human thenar muscles by and during brief
      discharge trains.
AB  - We investigated the influence of the history of activity on the contractile
      properties of abductor pollicis brevis (APB) to define how the forces produced by
      individual stimuli change within a stimulus train, with a view to clarifying the
      optimal discharge frequency for force production in brief trains. Supramaximal
      electrical stimuli were delivered to the median nerve at the wrist singly or in
      trains of 2-5 at various interstimulus intervals (ISIs). The force and
      electromyographic (EMG) responses to trains of n stimuli were defined by online
      subtraction of the responses to n - 1 stimuli. The force attributable to the nth
      stimulus was normalized to that produced by a single stimulus. The contraction
      force produced by 2 stimuli exceeded the force expected with linear summation of
      2 single twitches by 30-40% at ISIs of 2-100 ms. Increasing the number of stimuli
      resulted in less augmentation of the force produced by the last stimulus in the
      train for ISIs up to 20 ms, but greater augmentation for ISIs of 50-100 ms. At
      ISIs of less than 10 ms, the time to peak force produced by the last stimulus in
      a 5-pulse train was delayed by approximately 100 ms, the peak force produced by
      that stimulus was less than that produced by a single stimulus, and it occurred
      on the falling phase of the overall contraction. These properties are best
      explained by the catchlike property of muscle. This implies that the augmentation
      of contraction force due to this property can increase throughout a stimulus
      train, and is not restricted to the doublet discharges that have conventionally
      been studied. We conclude that, with brief discharge trains, maximal forces occur
      at ISIs of 56-75 ms, intervals that are longer than those conventionally
      associated with the catchlike property. Discharge rates of 15-20 HZ appear to be
      optimal for force generation by APB during steady contractions.

PMID- 16435343
TI  - Clinicopathological phenotype of ALS with a novel G72C SOD1 gene mutation
      mimicking a myopathy.
AB  - A 71-year-old woman with a family history of amyotrophic lateral sclerosis (ALS)
      was investigated for symmetrical, proximal limb and abdominal muscle weakness.
      Initial examination showed mild proximal muscle weakness in the arms and legs,
      slightly elevated serum creatine kinase (CK) level, and normal electromyographic
      (EMG) findings. A myopathy was the presumed diagnosis. Over the next year,
      weakness became severe and tendon reflexes became unelicitable; no upper motor
      signs were present. EMG then showed acute and chronic denervation and a muscle
      biopsy showed target fibers and grouped atrophy. DNA analysis revealed a G72C
      CuZn-superoxide dismutase (SOD1) mutation. Fasciculations were absent throughout
      the disease. The patient died 53 months after symptom onset and autopsy revealed
      loss of lower motor neurons (LMN) and SOD1-positive inclusions. This case expands
      the phenotypic spectrum of ALS associated with SOD1 mutations to include
      presenting features that mimic a myopathy.

PMID- 16435344
TI  - Randomized, placebo-controlled, double-blind clinical trial evaluating the
      treatment of plantar fasciitis with an extracoporeal shockwave therapy (ESWT)
      device: a North American confirmatory study.
AB  - Despite numerous publications and clinical trials, the results of treatment of
      recalcitrant chronic plantar fasciitis with extracorporeal shockwave therapy
      (ESWT) still remain equivocal as to whether or not this treatment provides relief
      from the pain associated with this condition. The objective of this study was to
      determine whether extracorporeal shock wave therapy can safely and effectively
      relieve the pain associated with chronic plantar fasciitis compared to placebo
      treatment, as demonstrated by pain with walking in the morning. This was set in a
      multicenter, randomized, placebo-controlled, double-blind, confirmatory clinical
      study undertaken in four outpatient orthopedic clinics. The patients, 114 adult
      subjects with chronic plantar fasciitis, recalcitrant to conservative therapies
      for at least 6 months, were randomized to two groups. Treatment consisted of
      approximately 3,800 total shock waves (+/-10) reaching an approximated total
      energy delivery of 1,300 mJ/mm(2) (ED+) in a single session versus placebo
      treatment. This study demonstrated a statistically significant difference between
      treatment groups in the change from baseline to 3 months in the primary efficacy
      outcome of pain during the first few minutes of walking measured by a visual
      analog scale. There was also a statistically significant difference between
      treatments in the number of participants whose changes in Visual Analog Scale
      scores met the study definition of success at both 6 weeks and 3 months
      posttreatment; and between treatment groups in the change from baseline to 3
      months posttreatment in the Roles and Maudsley Score. The results of this study
      confirm that ESWT administered with the Dornier Epos Ultra is a safe and
      effective treatment for recalcitrant plantar fasciitis.

PMID- 16435346
TI  - Altered knee kinematics in ACL-deficient non-copers: a comparison using dynamic
      MRI.
AB  - Kinematics measured during a short arc quadriceps knee extension exercise were
      compared in the knees of functionally unstable ACL-deficient patients, these
      patients' uninjured knees, and uninjured control subjects' knees. Cine phase
      contrast dynamic magnetic resonance imaging, in combination with a model-based
      tracking algorithm developed by the authors, was used to measure tibiofemoral
      kinematics as the subjects performed the active, supine posture knee extension
      exercise in the terminal 30 degrees of motion. Two determinants of tibiofemoral
      motion were measured: anterior/posterior location of the tibia relative to the
      femur, and axial rotation of the tibia relative to the femur. We hypothesized
      that more anterior tibial positioning, as well as differences in axial tibial
      rotation patterns, would be observed in ACL-deficient (ACL-D) knees when compared
      to uninjured knees. Multifactor ANOVA analyses were used to determine the
      dependence of the kinematic variables on (i) side (injured vs. uninjured, matched
      by subject in the control group), (ii) flexion angle measured at five-degree
      increments, and (iii) subject group (ACL-injured vs. control). Statistically
      significant anterior translation and external tibial rotation (screw home motion)
      accompanying knee extension were found. The ACL-D knees of the injured group
      exhibited significantly more anterior tibial positioning than the uninjured knees
      of these subjects (average difference over extension range=3.4+/-2.8 mm, p<0.01
      at all angles compared), as well as the matched knees of the control subjects.
      There was a significant effect of interaction between side and subject group on
      A/P tibial position. We did not find significant differences in external tibial
      rotation associated with ACL deficiency. The changes to active joint kinematics
      documented in this entirely noninvasive study may contribute to cartilage
      degradation in ACL-D knees, and encourage more extensive investigations using
      similar methodology in the future.

PMID- 16435345
TI  - Absolute serum hormone levels predict the magnitude of change in anterior knee
      laxity across the menstrual cycle.
AB  - This study aimed to determine whether absolute sex hormone concentrations predict
      the magnitude of knee joint laxity changes across the menstrual cycle. Twenty-two
      females (18-30 years, body mass index <or=30), who reported normal menstrual
      cycles for the previous 6 months were tested daily across one complete menstrual
      cycle for serum levels of estradiol (E=pg/mL), progesterone (P=ng/mL), and
      testosterone (T=ng/dL), and knee joint laxity (K(Lax)=mm displacement at 134N)
      measured with a standard knee arthrometer. The change in K(Lax) across the cycle
      (maximum-minimum), and minimum (early follicular) and peak (postovulatory)
      hormone concentrations were recorded for each subject. A stepwise linear
      regression determined if the minimum, peak, or absolute change in hormone
      concentrations would predict the magnitude of change in K(Lax) across the cycle.
      K(Lax) changed on average 3.2+/-1.1 mm across the menstrual cycle (range, 1.5-5.3
      mm). Minimum levels of E (39.9+/-11.8 pg/mL) and P (0.61+/-0.27 ng/mL), coupled
      with peak concentrations of E (199.6+/-54.9 pg/mL) and T (22.5+/-10.5 ng/dL)
      explained 57.6% of the change in K(Lax) across the cycle. Greater absolute
      changes in K(Lax) were observed in response to peak E and T levels when minimum E
      concentrations were lower and minimum P concentrations were higher in the early
      follicular phase. The absolute minimum concentrations of E and P in the early
      follicular phase appear to be important factors in determining the sensitivity of
      the knee joint's response to changing hormone levels.

PMID- 16435347
TI  - Expression of insulin-like growth factor binding proteins in healing tendon
      lesions.
AB  - he treatment of overuse tendon injuries with exogenous growth factors such as
      insulin-like growth factor-I (IGF-I) may facilitate an improved return to
      sustained athletic function. The biological effects of IGF-I are exerted under
      the control of a complex of IGF receptors, binding proteins, and proteases. This
      IGF system includes a family of six structurally related high-affinity IGF
      binding proteins (IGFBPs) that protect IGF-I from local proteases and restrict
      access of IGF-I to its receptor. This study describes the expression of the
      IGFBPs in flexor tendon after acute injury and during healing over time.
      Collagenase-induced lesions were created in the tensile region of the flexor
      digitorum superficialis tendon of both forelimbs of 14 horses. Tendons were
      harvested from euthanatized horses 1, 2, 4, 8, or 24 weeks following injury. Gene
      expression was quantitated by fluorescent real-time PCR, and protein expression
      was evaluated by Western ligand blot (WLB). Message for IGFBPs 2 to 6 was
      expressed in both normal and healing tendon. No IGFBP-1 mRNA was detected in
      equine tendon. Message expression for IGFBP-2, -3, and -4 increased following
      injury, whereas message expression for IGFBP-5 and -6 decreased. Protein
      expression for IGFBP-2, -3, and -4 was detected by WLB in normal tendon and
      showed a marked increase following injury. Protein for IGFBP-5 and -6 was not
      detectable by WLB in normal or healing tendon. The results of this study document
      the IGFBP response of flexor tendons to injury and healing, which provides
      information necessary for the design of protocols that may enhance tendon healing
      through manipulation of IGF-I ligand and binding protein levels.

PMID- 16435348
TI  - Pulsed ultrasound treatment accelerates the repair of Achilles tendon rupture in
      rats.
AB  - A rat tenotomy model was used to investigate the effect of combined conservative
      management and pulsed ultrasound (PUS) on the repair of tenotomized Achilles
      tendon. Hemitenotomy of right medial Achilles tendon was performed in 48 rats
      without suture, and patella tenotomy was performed to mimic immobilization and
      limb disuse of an injured limb. PUS and sham PUS were applied to the healing
      wound for the treatment group and control group for 5 min, 3 times per week for 2
      or 4 weeks, respectively. Tensile tests showed that the ultimate tensile strength
      (UTS) and stiffness of the repaired tendon in the treatment group at 2 weeks
      reached 48.92+/-8.39% and 62.48+/-32.46% of the contralateral normal tendon
      strength, which were significantly higher than those of the control group (UTS,
      30.36+/-15.46%; stiffness, 33.90+/-17.59; p<0.05). At 4 weeks, UTS increased to
      77.09+/-15.31% and stiffness to 92.48+/-31.12% in the treatment group,
      significantly higher than those in the control group (UTS, 54.33+/-18.40%,
      p<0.01; stiffness, 65.02+/-25.48%, p<0.05). Light microscopy revealed more
      regular, denser, and better aligned collagen fibers in the healing scar of the
      PUS-treated healing tendons. The findings suggested that PUS were able to
      accelerate the healing of the ruptured tendons.

PMID- 16435349
TI  - Delay of supraspinatus repair by up to 12 weeks does not impair enthesis
      formation: a quantitative histologic study in rabbits.
AB  - The purpose of this study was to find out whether supraspinatus repair delayed by
      up to12 weeks affects the formation of a new enthesis when compared to an
      immediate repair. In 67 rabbits, the supraspinatus fibrocartilaginous enthesis of
      one shoulder was resected. The tendon was attached to the greater tuberosity
      either immediately, after a 6-week, or after a 12-week delay. Five histologic
      variables were used to assess enthesis formation: number of non-chondrocytes,
      number of chondrocytes, alignment of chondrocytes in rows, area of metachromasia
      on toluidine blue (TB)-stained sections indicating proteoglycan content, and area
      of diffracted polarized light indicating spatial alignment of collagen fibers.
      For every variable, progressive enthesis formation was observed. Again, for every
      variable and at every time point studied, no statistically significant difference
      was observed between tendons repaired immediately, after 6, or after 12 weeks
      (all p>0.05). Supraspinatus tendon repairs delayed by 6 and 12 weeks constituted
      an enthesis which proceeded identically to one immediately repaired. Formation of
      a fibrocartilaginous enthesis depended on the elapsed time after repair and not
      on the duration between detachment and repair. Despite stated limitations, these
      results support both a trial of conservative treatment after a rotator cuff tear
      and a positive outcome of rotator cuff repair even if delayed by up to 12 weeks.

PMID- 16435350
TI  - Composition and transport properties of human ankle and knee cartilage.
AB  - The incidence of osteoarthritis is significantly higher in the knee as compared
      to the ankle, suggesting that differences in the properties of cartilage from
      these joints may contribute to the development of osteoarthritis. As an avascular
      tissue, articular cartilage depends primarily upon diffusion for molecular
      transport. The goal of this study was to determine if differences in the
      structure and composition between ankle and knee cartilage were also reflected as
      differences in solute transport properties. The diffusion coefficient and
      partition coefficient of a 70-kDa dextran molecule were measured in human ankle
      and knee articular cartilage using fluorescence recovery after photobleaching
      (FRAP) and were compared to the proteoglycan, collagen, water, and DNA contents
      within each zone. The mean partition coefficient was significantly lower in the
      ankle compared to the knee (0.010+/-0.002 vs. 0.022+/-0.003, p<0.01), but no
      differences in the diffusion coefficients were observed (34.6 +/- 0.9 microm(2)s(
      1) vs. 35.4+/-2.4 microm(2)s(-1), p=0.70). Ankle cartilage exhibited higher
      proteoglycan content as well as a trend toward lower water content, suggesting
      that ankle cartilage has a smaller effective pore size than knee cartilage. These
      findings suggest that differences in the composition of ankle and knee cartilage
      contribute to a difference in the partition coefficient. The results of this
      study provide further support for the hypothesis that the transport properties of
      cartilage may play a role in the differences in the incidence of osteoarthritis
      in these joints by altering the effective concentration of growth factors and
      cytokines to which chondrocytes are exposed.

PMID- 16435351
TI  - Anatomy of the posterolateral aspect of the goat knee.
AB  - The purpose of this study was to determine the anatomy of the posterolateral
      aspect of the goat knee for future in vivo studies using a goat model to examine
      the natural history of posterolateral knee injuries. Twelve non-paired, fresh
      frozen, adult goat knees were dissected to determine the anatomy of the
      posterolateral corner. The main posterolateral structures identified in the goat
      knee were the lateral collateral ligament, the popliteus muscle and tendon,
      popliteomeniscal fascicles, and the lateral gastrocnemius muscle. The lateral
      collateral ligament was extra-articular and coursed from its proximal attachment,
      located posterior and proximal to the lateral epicondyle, to its distal
      attachment on the lateral aspect of the fused proximal tibiofibula. The popliteus
      muscle attached to the medial edge of the posterodistal tibia, traveled
      anterolaterally, became intra-articular at its musculotendinous junction, and
      attached to the lateral femur just distal to the lateral epicondyle. Distinct
      popliteomeniscal fascicles attached the lateral meniscus to the popliteus muscle
      and tendon, and a fascial attachment from the musculotendinous junction of the
      popliteus muscle coursed to the lateral tibial plateau. This study provided
      information on the structures present in the posterolateral aspect of the goat
      knee and enhanced our understanding of their relationships to analogous
      structures in the human knee. This information is important to enable future
      development of potential models of the natural history of posterolateral knee
      injuries and also to test surgical techniques and the in vivo effects of these
      injuries on cruciate ligament reconstructions.

PMID- 16435352
TI  - Effect of cyclic strain and plating matrix on cell proliferation and integrin
      expression by ligament fibroblasts.
AB  - The role of cell surface integrins in cell migration, proliferation, and
      attachment to matrix molecules is well known. Integrin-matrix interactions have
      been implicated in mechanotransduction and load transmission from the outside to
      the inside of the cell. In this study, the effect of cyclic strain on the cell
      proliferation, attachment, and expression of integrin subunits beta1, beta3, and
      alpha5 was determined in anterior cruciate ligament (ACL) and medial collateral
      ligament (MCL) fibroblasts grown on polystyrene, Type I collagen, laminin,
      elastin, and fibronectin. ACL fibroblast proliferation was not affected by growth
      substrate whereas MCL cells reached confluence more rapidly on fibronectin
      compared with collagen or polystyrene. Exposure to 5% cyclic strain resulted in a
      significant decrease in ACL and MCL fibroblast proliferation on fibronectin and
      Type I collagen. MCL cells showed a greater strain-dependent inhibition of cells
      grown on a fibronectin substrate than those grown on collagen. This matrix
      dependent effect of strain on cell proliferation was not seen with ACL cells.
      Attachment of ACL and MCL fibroblasts was stronger to fibronectin compared with
      Type I collagen, laminin, and polystyrene. In the absence of applied load, the
      expression of beta1, beta3, and alpha5 subunits was not substrate dependent and
      the expression of beta1 and alpha5 integrin subunits was higher in MCL cells than
      ACL cells on all substrates. In contrast, the expression of beta3 integrin
      subunit was higher in ACL cells than MCL cells. In response to 5% strain, beta1,
      and alpha5 expression increased in all fibroblasts with MCL cells having a higher
      magnitude of expression. beta3 expression showed a 90% increase in response to
      load when grown on laminin for both MCL and ACL fibroblasts and demonstrated no
      change in expression on Type I collagen or fibronectin. The duration of applied
      strain from 2 versus 22 h had no effect on cell proliferation or integrin
      expression.

PMID- 16435353
TI  - Nitric oxide enhances collagen synthesis in cultured human tendon cells.
AB  - Collagen deposition is an important process that occurs during wound healing. We
      and others have shown that nitric oxide (NO) is important in tendon healing. The
      mechanisms whereby healing is enhanced are, however, undetermined. The aim of
      this study was to investigate whether NO could enhance collagen synthesis in
      cultured human tendon cells via exogenous NO and via an adenovirus containing the
      gene for inducible nitric oxide synthase (Ad-iNOS). Tendon cells from the torn
      edge of the tendons of patients undergoing rotator cuff repair surgery were
      cultured following collagenase digestion, and stimulated with exogenous NO
      (SNAP), transfected with Ad-iNOS, and treated with the NOS inhibitor, L-NMMA.
      Total protein and collagen synthesis were evaluated by (3)H-proline and
      collagenase sensitive (3)H-proline incorporation in human tendon cells. High
      doses of exogenous NO (SNAP) inhibited collagen synthesis. Lower doses enhanced
      total protein and collagen synthesis of the tendon cells. Ad-iNOS successfully
      transfected active iNOS into human tendon cells in vitro and also enhanced total
      protein and collagen synthesis of the tendon cells. The NOS inhibitor, L-NMMA,
      inhibited the effects of iNOS on the cells. Our studies show for first time that
      nitric oxide can enhance collagen synthesis in human tendon cells in vitro. These
      results may explain, in part, at least, the beneficial effects of NO donors in
      animal models and during the treatment of tendonopathies in human clinical
      trials. .

PMID- 16435354
TI  - Glucocorticoids inhibit tenocyte proliferation and Tendon progenitor cell
      recruitment.
AB  - Corticosteroid injection is commonly used to treat tendon injuries but is often
      associated with tendon rupture and impaired tendon healing. The effects of
      dexamethasone on tenocytes have been studied in vitro but only using high
      concentrations of dexamethasone in monolayer cultures of tenocytes over short
      periods of time. We have therefore investigated the effects of physiological and
      pharmacological concentrations of dexamethasone on monolayer cultures of
      tenocytes over extended time periods. We have also used fibroblastic-colony
      forming unit cultures to examine the effects of dexamethasone on a progenitor
      cell population located in tendons. Culturing tenocytes in the presence of
      dexamethasone for a period of 24 days resulted in a concentration-related
      decrease in cell number and collagen synthesis as compared to control cultures.
      This effect was time dependent with cell number in both dexamethasone-treated and
      control cultures leveling off after 14 days with the control cultures reaching
      higher cell densities. In contrast in control cultures, collagen accumulation
      continued to increase until week 4, whereas in the presence of dexamethasone,
      this tended to level off after 14 days. To study the role of progenitor cell
      recruitment, the effects of dexamethasone were investigated using the
      fibroblastic-colony forming unit assay. Treatment with dexamethasone at
      concentrations of 0.1 nM to 10 microM leads to a progressive reduction in mean
      colony size as compared to control cultures. Colony number remained constant at
      concentrations below 10 nM but fell progressively at concentrations above this.
      In conclusion, dexamethasone reduces both cell number and collagen synthesis in
      tenocyte cultures in a concentration-dependent manner by both direct effects on
      tenocyte proliferation and collagen accumulation, and also by modulating the
      recruitment of tendon progenitor cells.

PMID- 16435355
TI  - Causes of mechanically induced collagen damage in articular cartilage.
AB  - Osteoarthritis (OA) is a multifactorial disease, associated with articular
      cartilage degeneration and eventually joint destruction. The phases of the
      disease have been described in detail, and mechanical factors play an important
      role in the initiation of OA, but many questions remain about its etiology.
      Swelling of cartilage, one of the earliest signs of damage, is proportional to
      the amount of collagen damage. This strongly suggests that damage to the collagen
      network is an early event in cartilage degeneration. The goal of this study was
      to determine the mechanical cause of early collagen damage in articular cartilage
      after mechanical overloading. Both the shear strain along the fibrils and the
      maximum fibril strains were evaluated as possible candidates for causing collagen
      damage. This evaluation was done by comparing the locations of maximum shear and
      tensile strains with the locations of initial collagen damage after mechanical
      overloading in bovine explants as found using antibodies directed against
      denatured type II collagen (Col2-3/4M). Collagen damage could be initiated by
      excessive shear strains along the collagen fibrils, and by excessive fibrils
      strains. The locations of collagen damage after mechanical overloading were
      highly dependent on the cartilage thickness, with thinner cartilage being more
      susceptible to damage than thicker samples.

PMID- 16435356
TI  - Modulation of endochondral development of the distal femoral condyle by
      mechanical loading.
AB  - Although previous theoretical modeling studies have predicted that various
      mechanical stresses accelerate or inhibit the ossification process of the
      neonatal chondroepiphysis, there is a paucity of experimental data to verify
      these models. The present study was designed to provide experimental evidence on
      whether the ossification of the chondroepiphysis is modulated by mechanical
      loading on the distal femoral condyle explant of the neonatal (5-day-old) rabbit
      in organ culture. Upon aseptic dissection, the right condyle explant was immersed
      in and fixated to an organ culture system, and received cyclic forces at 200 mN
      and 1 Hz for 12 h (N=8) directly on its slightly convex articular surface,
      whereas the contralateral, left condyle explant was immersed separately in organ
      culture (N=8). Subsequently, both loaded and control explants were placed in a
      bioreactor rotating at 20 rpm for 72 h. In each mechanically loaded specimen, a
      structure reminiscent of the secondary ossification center (SOC) appeared with an
      average area of 1.17+/-0.13 mm(2), or 15.2+/-8.2% of the total epiphysis area. In
      contrast, no SOC was detected in any of the unloaded contralateral control
      specimens. The SOC in mechanically loaded specimens was stained intensively with
      fast green, whereas either the rest of the loaded epiphysis or the entire control
      epiphysis was stained intensely to safranin-O but lacked fast green staining.
      Immunolocalization revealed that the SOC of the mechanically loaded specimens
      expressed Run x 2 and osteopontin, both of which were absent in the unloaded
      control specimens. Type X collagen was expressed surrounding hypertrophic
      chondrocytes adjacent to the SOC, but was absent in the control specimen. Type II
      collagen and decorin were absent in the SOC of the loaded specimen, but were
      expressed throughout the rest of the loaded epiphysis and the unloaded control
      epiphysis. The intensity of type II collagen and decorin expression was
      significantly stronger among hypertrophic chondrocytes surrounding the SOC than
      the control. The numbers of hypertrophic chondrocytes surrounding the SOC and
      superior to metaphyseal bone were significantly higher in the loaded specimens
      than the unloaded controls. Taken together, mechanical stresses accelerate the
      formation of the secondary ossification center, and therefore modulate
      endochondral ossification.

PMID- 16435357
TI  - Exposure of mouse preosteoblasts to pulsed electromagnetic fields reduces the
      amount of mature, type I collagen in the extracellular matrix.
AB  - We tested the hypothesis that exposure of a mouse preosteoblast cell line to
      pulsed electromagnetic fields (PEMF) would affect components of the extracellular
      matrix. We report that exposure of MC3T3-E1 cells to a single PEMF waveform
      significantly reduced the amount of mature, alpha1(I) collagen in the
      extracellular matrix (ECM) and the conditioned medium, without affecting the
      amount of total ECM protein. This decrease was not due to changes in the steady
      state level of Col1A1 mRNA or to degradation of mature collagen. We then tested
      the effect of three distinct PEMF waveforms, two orthogonal coil orientations,
      and two waveform amplitude levels on the amount of alpha1(I) collagen in the
      conditioned medium. A sequence of factorial ANOVAs and stepwise regression
      modeling revealed that the period (duration) of the individual pulses accounted
      for a significant proportion of the variance associated with the amount of
      alpha1(I) collagen in the conditioned medium. The total variance accounted for,
      however, was small (R(2)=0.155, p<0.001 and R(2)=0.172, p<0.001, in the
      horizontal and vertical orientations, respectively). The positive and negative
      regression coefficients for the coil orientations revealed that the influence of
      pulse period was significantly different for the orthogonal coil orientations
      (p<0.001). The findings imply that the dominant influence of PEMF on the amount
      of mature, alpha1(I) collagen in the ECM is related to variables other than those
      expressed in the time-amplitude domain. The results provide objective direction
      toward identifying waveform characteristics that contribute to the observed
      between-waveform differences with regard to collagen. Advances in this area may
      lead toward improving waveforms and waveform delivery protocols.

PMID- 16435358
TI  - CYR61 (CCN1) protein expression during fracture healing in an ovine tibial model
      and its relation to the mechanical fixation stability.
AB  - The formation of new blood vessels is a prerequisite for bone healing. CYR61
      (CCN1), an extracellular matrix-associated signaling protein, is a potent
      stimulator of angiogenesis and mesenchymal stem cell expansion and
      differentiation. A recent study showed that CYR61 is expressed during fracture
      healing and suggested that CYR61 plays a significant role in cartilage and bone
      formation. The hypothesis of the present study was that decreased fixation
      stability, which leads to a delay in healing, would lead to reduced CYR61 protein
      expression in fracture callus. The aim of the study was to quantitatively analyze
      CYR61 protein expression, vascularization, and tissue differentiation in the
      osteotomy gap and relate to the mechanical fixation stability during the course
      of healing. A mid-shaft osteotomy of the tibia was performed in two groups of
      sheep and stabilized with either a rigid or semirigid external fixator, each
      allowing different amounts of interfragmentary movement. The sheep were
      sacrificed at 2, 3, 6, and 9 weeks postoperatively. The tibiae were tested
      biomechanically and histological sections from the callus were analyzed
      immunohistochemically with regard to CYR61 protein expression and
      vascularization. Expression of CYR61 protein was upregulated at the early phase
      of fracture healing (2 weeks), decreasing over the healing time. Decreased
      fixation stability was associated with a reduced upregulation of the CYR61
      protein expression and a reduced vascularization at 2 weeks leading to a slower
      healing. The maximum cartilage callus fraction in both groups was reached at 3
      weeks. However, the semirigid fixator group showed a significantly lower CYR61
      immunoreactivity in cartilage than the rigid fixator group at this time point.
      The fraction of cartilage in the semirigid fixator group was not replaced by bone
      as quickly as in the rigid fixator group leading to an inferior histological and
      mechanical callus quality at 6 weeks and therefore to a slower healing. The
      results supply further evidence that CYR61 may serve as an important regulator of
      bone healing.

PMID- 16435359
TI  - Low intensity pulsed ultrasound accelerated bone remodeling during consolidation
      stage of distraction osteogenesis.
AB  - Bone regeneration in distraction osteogenesis occurs under tensile stress with
      axial rhythmic distraction after osteotomy. In this study, we evaluated if the
      low intensity pulsed ultrasound (LIPUS) was also effective on enhancement of bone
      remodeling during consolidation stage of distraction osteogenesis. Open osteotomy
      of seventeen 18-week-old female New Zealand rabbit tibiae were performed. The
      distraction was applied with the rate of 1 mm per day. LIPUS (30 mW/cm(2), 1.5
      MHz) was delivered for 20 min per day during 4-week consolidation stage (n=10).
      The animals without treatment served as sham group (n=7). Plain X-ray, peripheral
      quantitative computational tomography (pQCT), and torsional test were performed.
      Results showed that smaller radiolucent interzone of LIPUS treatment group was
      gradually occupied by calcified tissue in plain X-ray at week 2. The bone mineral
      density (BMD) measured on radiographs increased by 9.18% in the LIPUS group. Bone
      mineral content (BMC), hard callus volume, and bone strength index (BSI) measured
      by pQCT were 83%, 116%, and 94%, respectively, in LIPUS group that were
      significantly greater than those of the controls. At the 4th week, LIPUS-treated
      callus showed the development of neocorticalization in the proximal and distal
      region. The BMC, hard callus volume, and BSI of LIPUS group decreased and was not
      significantly different from control. This was also confirmed by the maximum
      torque of LIPUS-treated callus (1424.2+/-457.3 N . mm) obtained at week 4, which
      did not differ from that of the sham group (1968.8+/-895.1 N . mm). In
      conclusion, the effective period of LIPUS treatment was at the initial stage of
      consolidation, with accelerated bone formation and remodeling.

PMID- 16435360
TI  - Effect of impact assembly on the fretting corrosion of modular hip tapers.
AB  - The goal of this study was to determine the effect of assembly load and local
      assembly environmental conditions on the fretting corrosion of modular femoral
      stem tapers. Femoral head/taper assemblies in both similar (CoCrMo/CoCrMo) and
      mixed (CoCrMo/Ti-6Al-4V) alloy combinations were evaluated using an
      electrochemical test method. Specimens were assembled under impact loading and by
      hand, in both wet and dry conditions. Incremental cyclic loads ranging from 89 to
      5,340 N were applied at a frequency of 3 Hz in Ringer's solution at ambient
      temperature. During the test, both the open circuit potential (OCP) and fretting
      current (i(fret)) were measured using a saturated calomel electrode (SCE) and
      counter electrode, respectively. The results were comparable for both mixed and
      similar alloy couples. Decreases in OCP and increases in i(fret) (indicators of
      oxide film fracture and repassivation) were seen with increasing load magnitude,
      often occurring at loads well below those expected clinically. OCP at the 5,340 N
      cyclic load ranged from -30.4 to -103.7 mV versus SCE for similar alloy couples,
      and -19.1 to -181.4 mV versus SCE for mixed alloy couples. Mean peak fretting
      currents ranged from 0.84 to 1.42 microA and 1.06 to 3.12 microA for similar and
      mixed alloy couples, respectively. The larger current magnitudes and more
      negative shifts in OCP for mixed alloy couples indicate the difference in oxide
      film fracture behavior between titanium and cobalt alloys. The load at which OCP
      began to drop (onset of fretting) was dependent upon the assembly conditions for
      both material couples. Specimens assembled with impact loads in air showed the
      highest resistance to fretting. The results of this study indicate that the
      assembly load and the environment both play a role in the initial stability of
      modular hip taper connections.

PMID- 16435361
TI  - Erythromycin inhibits wear debris-induced inflammatory osteolysis in a murine
      model.
AB  - Up to 20% of patients with total joint arthroplasty will develop radiographic
      evidence of aseptic loosening (AL), which most likely results from an
      inflammatory response to billions of wear debris shed from the implant. Our
      previous work has demonstrated that erythromycin (EM), a macrolide antibiotic,
      inhibits wear debris-induced inflammatory osteoclastogenesis through the
      reduction of cytokine production and osteoclast differentiation, both of which
      involve the NF-kappaB pathway. The aim of the current study was to determine
      whether EM inhibits wear debris-induced inflammatory osteolysis in a murine
      osteolysis model. Ultrahigh molecular-weight polyethylene (UHMWPE) debris was
      introduced into established air pouches on BALB/c mice, followed by implantation
      of calvaria bone from syngeneic littermates. EM (2 mg/kg/day) was given to mice
      intraperitoneally 2 days before UHMWPE introduction and maintained until the
      sacrifice of the mice. Mice with and without EM treatment, as well as control
      mice injected with saline alone were included in this study. Pouch tissues were
      collected 14 days after UHMWPE inoculation for molecular and histology analysis.
      Our findings indicate that: (1) EM reduced UHMWPE-induced tissue inflammation,
      including the diminished pouch membrane thickness, reduced inflammatory cellular
      infiltration, and lowered IL-1beta and TNF-alpha expression (mRNA and protein);
      (2) EM inhibited UHMWPE-induced osteoclastogenesis, with reduced gene activation
      of RANK, RANKL, and CPK, and diminished RANKL expression in UHMWPE stimulated
      pouches, and (3) EM markedly reduced the number of TRAP(+) cells in pouch
      tissues, and protected against bone collagen depletion. In conclusion, this study
      provides the evidence that EM inhibits the UHMWPE particles-induced inflammatory
      osteolysis in a murine model, and represents a promising therapeutic candidate
      for the prevention and treatment of AL.

PMID- 16435362
TI  - Antimicrobial efficacy of gentamicin-loaded acrylic bone cements with fusidic
      acid or clindamycin added.
AB  - The increasing gentamicin resistance among bacteria in septic joint arthroplasty
      has stimulated interest in adding a second antibiotic into gentamicin-loaded bone
      cement. A first aim of this in vitro study is to investigate whether addition of
      fusidic acid or clindamycin to gentamicin-loaded bone cement has an additional
      antimicrobial effect against a collection of 38 clinical isolates, including 16
      gentamicin-resistant strains. A modified Kirby-Bauer test, involving measurement
      of the inhibition zone around antibiotic-loaded bone cement discs on agar plates,
      was used to investigate whether adding a second antibiotic has an additional
      antimicrobial effect. Second, a selected number of strains was used to study
      their survival in an interfacial gap made in the different bone cements to mimic
      the gap between bone and cement as existing near a prosthesis. Gentamicin-loaded
      bone cement had an antimicrobial activity against 58% of the 38 bacterial strains
      included in this study, while 68% of the strains were affected by bone cement
      loaded with a combination of gentamicin and clindamycin. Bone cement loaded with
      the combination of gentamicin and fusidic acid had antimicrobial activity against
      87% of the bacterial strains. In the prosthesis-related gap model, there was a
      clear trend toward less bacterial survival for gentamicin-loaded bone cement
      after adding clindamycin or fusidic acid. Addition of clindamycin or fusidic acid
      into gentamicin-loaded bone cement yields an additional antimicrobial effect. The
      combination gentamicin and fusidic acid was effective against a higher number of
      clinical isolates than the combination of gentamicin with clindamycin, including
      gentamicin-resistant strains.

PMID- 16435363
TI  - GAP-43 heterozygous mice show delayed barrel patterning, differentiation of
      radial glia, and downregulation of GAP-43.
AB  - GAP-43 heterozygous (HZ) mice exhibit abnormal thalamocortical pathfinding,
      fasciculation, and terminal arborization at postnatal day 7 (P7). Here we tested
      whether these defects are correlated with delayed development of HZ cortical
      patterns. We assessed the rate of barrel segregation and radial glia
      differentiation in wild-type (WT) and HZ cortices. Since GAP-43 is involved in
      some forms of neural plasticity, we also compared the duration of the critical
      period for lesion-induced plasticity in both genotypes. Cytochrome oxidase
      histochemistry revealed a delay of approximately 1 day in barrel pattern
      formation in GAP-43 HZ mice. GAP-43 WT barrels showed complete segregation
      between P2-P3, while HZ barrels did not reach the same level of segregation until
      P3-P4. We found a similar delay in the transformation of radial glia from
      monopolar to multipolar phenotypes, from P5 in WT to P7 in HZ cortex. Radial
      glial cells represent many of the neuronal progenitors in developing cortex and
      aid in cell migration. Thus, the delay in radial glial differentiation may
      contribute to the delay in HZ barrel segregation. Interestingly, we found no
      change in the extent of the critical period for HZ cortical responsiveness to
      early peripheral damage or in the time course of the cortical response. As
      expected, GAP-43 expression in HZ cortex is significantly reduced early in
      development. However, HZ GAP-43 expression remains at maximum levels after P9,
      when it is normally downregulated. As a result, HZ GAP-43 expression is near
      normal by P26, by which time near-normal barrel dimensions have been restored.
      Our findings indicate that GAP-43 deficiency leads to early delays in barrel
      development and suggest that these failures are followed by homeostatic
      responses, including prolonged GAP-43 expression. These compensatory mechanisms
      may rescue normal cortical reorganization in neonates and near-normal barrel
      morphology and GAP-43 expression in adulthood.

PMID- 16435364
TI  - Acrylic polymers as thickening agents for tetraglycol cosolvent.
AB  - This article evaluated the thickening properties of two different Eudragits, L
      and RS, in tetraglycol cosolvent in order to obtain high viscosity systems
      characterized by controlled release properties. Tetraglycol was chosen for its
      ability to dissolve a wide range of water insoluble drugs, while Eudragit RS and
      L for their specific dissolution and permeability properties under physiological
      conditions. Study of the rheological properties was performed to characterize
      elastic and viscous properties of Eudragit/tetraglycol samples in function of
      frequency and temperature. For all systems, the results outlined a liquid like
      behavior, as observed for dilute polymer solutions. In fact the fitting of the
      log G'-log G'' versus frequency curves showed a good agreement with the Rouse or
      Zimm models. So despite the increase in viscosity, samples still behaved like
      liquid systems. After the addition of paracetamol the release characteristics
      were defined pointing out the great release control properties of both Eudragit L
      and RS, which showed different release kinetics depending on the pH of the
      environment. Semisolid Eudragits/tetraglycol systems can be considered as a new
      alterative for the sustained release of insoluble or poorly water-soluble drugs.

PMID- 16435365
TI  - Rough set-based proteochemometrics modeling of G-protein-coupled receptor-ligand
      interactions.
AB  - G-Protein-coupled receptors (GPCRs) are among the most important drug targets.
      Because of a shortage of 3D crystal structures, most of the drug design for GPCRs
      has been ligand-based. We propose a novel, rough set-based proteochemometric
      approach to the study of receptor and ligand recognition. The approach is
      validated on three datasets containing GPCRs. In proteochemometrics, properties
      of receptors and ligands are used in conjunction and modeled to predict binding
      affinity. The rough set (RS) rule-based models presented herein consist of
      minimal decision rules that associate properties of receptors and ligands with
      high or low binding affinity. The information provided by the rules is then used
      to develop a mechanistic interpretation of interactions between the ligands and
      receptors included in the datasets. The first two datasets contained descriptors
      of melanocortin receptors and peptide ligands. The third set contained
      descriptors of adrenergic receptors and ligands. All the rule models induced from
      these datasets have a high predictive quality. An example of a decision rule is
      "If R1_ligand(Ethyl) and TM helix 2 position 27(Methionine) then Binding(High)."
      The easily interpretable rule sets are able to identify determinative receptor
      and ligand parts. For instance, all three models suggest that transmembrane helix
      2 is determinative for high and low binding affinity. RS models show that it is
      possible to use rule-based models to predict ligand-binding affinities. The
      models may be used to gain a deeper biological understanding of the combinatorial
      nature of receptor-ligand interactions.

PMID- 16435366
TI  - Expression pattern and functional characterization of connexin29 in transgenic
      mice.
AB  - Using newly generated transgenic mice in which the coding region of the
      connexin29 (Cx29) gene was replaced by the lacZ reporter gene, we confirmed
      previous immunochemical results that Cx29 is expressed in Schwann cells,
      oligodendrocytes and Bergmann glia cells. In addition, we detected lacZ/Cx29 in
      Schwann cells of the sciatic nerve and in particular of the spiral ganglion in
      the inner ear, as well as at low abundance in the stria vascularis. Furthermore,
      we found lacZ/Cx29 expression in nonmyelinating Schwann cells of the adrenal
      gland, in chondrocytes of intervertebral discs and the epiphysis of developing
      bones. Electron microscopic analyses of myelin sheaths in the central and
      peripheral nervous system of Cx29-deficient mice detected no abnormalities. The
      nerve conduction in the sciatic nerve of adult Cx29-deficient mice and the
      auditory brain stem response as well as visually evoked potentials in 4- to 10
      week-old Cx29-deficient mice were not different from wild-type littermate
      controls. Thus, in contrast to connexin32 and connexin47, which are also
      expressed in myelinating cells, Cx29 does not contribute to the function of
      myelin in adult mice.

PMID- 16435367
TI  - Chemical kinetics and aqueous degradation pathways of a new class of synthetic
      ozonide antimalarials.
AB  - Chemical stability of a new class of ozonide (1,2,4 trioxolanes) antimalarial
      compounds was investigated. The effects of pH, ionic strength, dielectric
      constant and cyclodextrin-complexation on the chemical stability and degradation
      product formation of selected compounds were examined. The mechanism of
      degradation in aqueous solution was probed using (18)O-labelled water and kinetic
      solvent isotope effect studies. The effect of stereochemistry was investigated
      using selected pairs of stereoisomers. The degradation of the ozonides in aqueous
      solution followed apparent first-order kinetics, with no effect of ionic strength
      and no indication of any direct involvement of water in the degradation
      mechanism. All major degradation products were identified and mass balance was
      confirmed. Stereochemistry had a significant effect on degradation rate; trans
      isomers degrading approximately four-fold faster than the corresponding cis
      isomers. The degradation rates were essentially independent of pH above pH 2;
      however, an additional specific acid catalysed pathway was dominant below pH 2.
      Solvent dielectric constant had a significant effect on the degradation rate. It
      is proposed that the degradation observed in aqueous solution occurred through a
      concerted heterolytic scission of the central ozonide ring, with chemical
      substituents on the cyclohexyl ring having only a minor influence on degradation
      rate.

PMID- 16435368
TI  - Regionally specific distribution of the binding of anti-glutamine synthetase and
      anti-S100 antibodies and of Datura stramonium lectin in glial domains of the
      optic lobe of the giant prawn.
AB  - We previously characterized some crustacean glial cells by markers such as 2',3'
      cyclic nucleotide 3'-phosphodiesterase and glial fibrillary acidic protein. Here
      we use antibodies against glutamine synthetase full-length molecule (anti-GS/FL),
      a GS C-terminal peptide (anti-GS/20aa-C), and brain S100 (anti-S100), as well as
      the binding of the insect glia and rat astrocytic marker Datura stramonium lectin
      (DSL), in the optic lobe of the prawn Macrobrachium rosenbergii. All markers
      label the lamina ganglionaris cartridge region (lighter: anti-GS/FL; heavier:
      DSL). In addition, anti-GS/FL labels superficial somata of external and internal
      medullas and internal chiasm cells. Both anti-GS/20aa-C and anti-S100 label
      heavily the glial sheaths of the lamina ganglionaris. In addition, anti-S100
      binds to the perineurial glia of medullary parenchymal vessels. Western blot
      analyses show that both anti-GS/FL and anti-GS/20aa-C bind mostly to a band of 50
      55 kDa, compatible with a long isoform of vertebrate GS, and accessorily to a
      possible dimer and, in the case of anti-GS/20aa-C, to an ill-defined band of
      intermediate mass. Binding of anti-S100 is selective for a single band of about
      68 kDa but shows no protein in the weight range of the canonical S100 protein
      superfamily. DSL reveals two bands of about 75 and about 120 kDa, thus within the
      range of maximal recognition for rat astrocytes. Our results suggest that
      phenotype protein markers of the optic lobe glia share antigenic determinants
      with S100 and (a long form of) GS and that, similarly to vertebrate and insect
      glia, crustacean glia protein and N-glycan residue markers display regional
      heterogeneity.

PMID- 16435369
TI  - Towards computing with proteins.
AB  - Can proteins be used as computational devices to address difficult computational
      problems? In recent years there has been much interest in biological computing,
      that is, building a general purpose computer from biological molecules. Most of
      the current efforts are based on DNA because of its ability to self-hybridize.
      The exquisite selectivity and specificity of complex protein-based networks
      motivated us to suggest that similar principles can be used to devise biological
      systems that will be able to directly implement any logical circuit as a parallel
      asynchronous computation. Such devices, powered by ATP molecules, would be able
      to perform, for medical applications, digital computation with natural interface
      to biological input conditions. We discuss how to design protein molecules that
      would serve as the basic computational element by functioning as a NAND logical
      gate, utilizing DNA tags for recognition, and phosphorylation and exonuclease
      reactions for information processing. A solution of these elements could carry
      out effective computation. Finally, the model and its robustness to errors were
      tested in a computer simulation.

PMID- 16435370
TI  - Terminal-group effects on the folding behavior of selected beta-peptides.
AB  - It has been suggested that the stability of a beta-peptide helical fold is
      affected by the interplay between the electrical charge of terminal groups and
      the dipole due to the helical conformation, the so-called charge-dipole
      stabilization; the numerical simulations presented herein test that suggestion.
      The motions of two beta-peptide oligomers, each of which has been shown by NMR
      spectroscopy to fold into a different helical conformation, have been simulated.
      The simulated motions bear out empirical observations as to the effect of
      chemical protection of terminal groups on the stability of beta-peptide helical
      folds and they support the hypothesis of charge-dipole stabilization.

PMID- 16435371
TI  - Crystal structure of a single-stranded DNA-binding protein (TM0604) from
      Thermotoga maritima at 2.60 A resolution.

PMID- 16435372
TI  - Protein kinase resource: an integrated environment for phosphorylation research.
AB  - The protein kinase superfamily is an important group of enzymes controlling
      cellular signaling cascades. The increasing amount of available experimental data
      provides a foundation for deeper understanding of details of signaling systems
      and the underlying cellular processes. Here, we describe the Protein Kinase
      Resource, an integrated online service that provides access to information
      relevant to cell signaling and enables kinase researchers to visualize and
      analyze the data directly in an online environment. The data set is synchronized
      with Uniprot and Protein Data Bank (PDB) databases and is regularly updated and
      verified. Additional annotation includes interactive display of domain
      composition, cross-references between orthologs and functional mapping to OMIM
      records. The Protein Kinase Resource provides an integrated view of the protein
      kinase superfamily by linking data with their visual representation. Thus, human
      kinases can be mapped onto the human kinome tree via an interactive display.
      Sequence and structure data can be easily displayed using applications developed
      for the PKR and integrated with the website and the underlying database. Advanced
      search mechanisms, such as multiparameter lookup, sequence pattern, and blast
      search, enable fast access to the desired information, while statistics tools
      provide the ability to analyze the relationships among the kinases under study.
      The integration of data presentation and visualization implemented in the Protein
      Kinase Resource can be adapted by other online providers of scientific data and
      should become an effective way to access available experimental information.

PMID- 16435373
TI  - Early embryonic death-associated changes in genome-wide gene expression profiles
      in the fetal placenta of the cow carrying somatic nuclear-derived cloned embryo.
AB  - Successful somatic nuclear transfer-derived cloning has been reported in cattle;
      however, the cloned embryo is highly susceptible to death around day 60 of
      gestation leading to early embryonic loss. The early embryonic death is
      postulated to possibly arise in part from an atypical placentation. We have
      performed cDNA macroarray analysis using 3,353 of the previously cataloged 4,165
      genes, in order to characterize the early embryonic death-associated changes in
      genome-wide gene expression profiles in the fetal placenta of the cow carrying
      somatic nuclear transfer-derived cloned embryo. A more marked difference in the
      expression profiles was observed between the fetal placentas of the cows with the
      cloned immotile embryo (CD) and with the cloned motile embryo (CL) or artificial
      insemination-derived motile embryo (AI), as compared to between the CL and AI
      placentas, suggesting an aberration of the expression profile in the CD placenta
      among the three placentas. Further, 291 and 77 genes showed more than twofold
      elevation and less than 50% reduction, respectively, in either or both of two CD
      (CD1 and CD2) placentas in comparison with the CL placenta, but no differential
      expression between the CL and AI placentas. The expression patterns of six genes
      in the AI, CL, and CD placentas were confirmed in an experiment with an
      additional sample for each of the three placentas. Among the placental genes
      showing the early embryonic death-associated changes of expression in the cow
      with the cloned embryo, IGF2 (elevated gene), and HBA1, HBA2, SPTB, and SPTBN1
      genes (reduced gene) are intriguing in that the changes of expression in these
      genes were observed in an additional sample of CD placenta as well as the CD1 and
      CD2 placentas, and in that overexpression (for IGF2) and dysfunction or
      deficiency (for HBA1, HBA2, SPTB, and SPTBN1) result in embryonic lethality.

PMID- 16435374
TI  - Bovine corpus luteum is an extrapituitary site of prolactin production.
AB  - Prolactin (PRL) is known to be synthesized not only in the anterior pituitary,
      but also in other organs including the ovary. Among its various functions, PRL is
      regarded as the most important constituent of the luteotropic complex in rodents
      and pigs. The purpose of the present study was to determine whether PRL is
      produced locally in bovine corpus luteum (CL) and to determine its possible roles
      in CL. In the present study, we examined changes during the luteal phase in (1)
      the expressions of PRL and PRL receptors (long form: l-PRLR, short form: s-PRLR)
      in CL and (2) the localization of PRL in CL. We also measured the levels of PRL
      mRNA in cultured luteal cells and luteal endothelial cells. Furthermore, the
      effect of PRL on progesterone (P4) and prostaglandin (PG) F2alpha production by
      cultured bovine luteal cells was examined. Semiquantitative RT-PCR analysis
      revealed that the mRNAs for PRL and its two receptors, l- and s-PRLR, were
      expressed in all luteal stages examined. PRL mRNA expression was less in the
      regressed stage (days 19-21 after ovulation) than in the other stages. Both l
      PRLR and s-PRLR mRNA expressions were higher in the late luteal stage (days 15
      17) than in the other stages, while the ratio of l-PRLR to s-PRLR was less in the
      regressed stage than in the other stages. PRL mRNA was also detected in cultured
      luteal cells and luteal endothelial cells. PRL protein was immunohistochemically
      detected only in CL of the mid- and regressed stages. It was detected in smooth
      muscle cells of the intraluteal arterioles and endothelial cells but not in
      luteal cells and other cell types of CL. Exposure of cultured luteal cells
      obtained from mid-stage CL (days 8-12) to bovine PRL (100, 200 ng/ml) for 24 hr
      did not affect P4 and PGF2alpha production by the cells. The present study
      demonstrates for the first time the expressions of PRL and PRLR mRNA in bovine CL
      throughout the luteal phase. The overall results strongly suggest that the bovine
      CL is an extrapituitary site of PRL production.

PMID- 16435375
TI  - In vivo expression of interferon tau mRNA by the embryonic trophoblast and
      uterine concentrations of interferon tau protein during early pregnancy in the
      cow.
AB  - In this study, we have measured uterine concentrations of interferon tau and
      intensity of embryonic interferon tau mRNA expression between day 14 and 18 in
      cows. While interferon tau concentrations rose dramatically (P < 0.001) from day
      14 to 18, there was no significant increase in the intensity of expression of
      interferon tau mRNA by the trophoblast. When results were analyzed on the basis
      of embryo size, well elongated embryos (>10 cm) produced significantly (P <
      0.001) more interferon tau than smaller embryos but showed similar levels of
      interferon tau mRNA expression. These results demonstrate that the increase in
      interferon tau concentrations responsible for the maternal recognition of
      pregnancy results from the increase in embryo size during elongation and not from
      any upregulation of mRNA expression.

PMID- 16435376
TI  - The utility of GLUT-1 immunolocalization in cell blocks: An adjunct to the fine
      needle aspiration diagnosis of cystic squamous lesions of the head and neck.
AB  - BACKGROUND: Cytologic distinction of metastatic cystic squamous cell carcinoma
      (SCC) from benign squamous cell lesions, especially the ones with superimposed
      inflammatory atypia, can be very challenging. The authors evaluated the
      usefulness of glucose transporter-1 (GLUT-1) immunostaining as an adjunct to fine
      needle aspirations of squamous lesions of the head and neck. METHODS:
      Immunohistochemical staining for GLUT-1 was performed on paraffin-embedded cell
      blocks of 28 cases with the following cytologic diagnoses: 1) metastatic SCC (11
      cases); 2) atypical squamous cells, SCC [corrected] cannot be excluded (6 cases);
      and 3) cytologic findings consistent with branchial cleft cyst (BCC) (11 cases).
      RESULTS: All 11 cases with an unequivocal cytologic diagnosis of metastatic SCC
      were positive for GLUT-1. Tissue follow-up confirmed metastatic SCC in all 11
      cases. The squamous cells in all 11 cases with cytologic findings consistent with
      BCC were negative for GLUT-1; tissue follow-up confirmed diagnoses of BCC in 8
      cases. In the remaining 3 cases, excision was not performed, and, clinically, no
      recurrences were identified at 28, 20, and 16 months of follow-up. Of the 6 cases
      with cytologic diagnosis of atypical squamous cells, 3 were negative and 3 were
      positive for GLUT-1. Subsequent excisional biopsies in these cases revealed 4
      cases of metastatic SCC (3 positive and 1 negative for GLUT-1), 1 case of BCC
      (negative for GLUT-1), and 1 case of thyroglossal duct cyst (negative for GLUT
      1). CONCLUSION: GLUT-1 immunostaining is a useful adjunct in differentiating
      benign and malignant squamous lesions in cell-block material. Although negative
      staining for GLUT-1 does not exclude malignancy, positive immunoreactivity for
      GLUT-1 may aid in accurate diagnosis of malignancy in cytomorphologically
      equivocal squamous lesions of the head and neck.

PMID- 16435377
TI  - Medical and non-medical barriers to outpatient treatment of fever and neutropenia
      in children with cancer.
AB  - BACKGROUND: A number of clinical trials have employed clinical criteria that can
      identify pediatric patients at low-risk for complicated episodes of fever and
      neutropenia (F&N) and have successfully treated low-risk patients in the
      outpatient setting. Despite this, inpatient management remains the standard of
      care. This trial tested the hypothesis that a strategy of initial hospitalization
      followed by continuation of therapy in the outpatient setting could be
      practically implemented in the majority of episodes. PROCEDURE: Patients
      presenting with F&N were initially evaluated to determine if they had high-risk
      clinical criteria that would exclude them from this approach. Eligible patients
      were then hospitalized and treated with iv antibiotics. On subsequent days the
      attending physician determined whether the patient had exhibited improvement and
      could continue therapy in the outpatient setting with oral antibiotics.
      Outpatients were seen three times weekly and continued antibiotics until recovery
      from F&N. RESULTS: Outpatient oral antibiotic therapy was practically implemented
      in less than one-quarter of episodes of pediatric F&N. Forty-nine percent of
      episodes were excluded from study by medical and social protocol exclusion
      criteria. One hundred five episodes were enrolled and among these 59 episodes
      included outpatient management. Common barriers to outpatient care included
      serious medical comorbidities, non-medical barriers including language and
      distance of residence from the medical center, and lack of interest. The average
      duration of outpatient care was 3.6 days following an average of 3.5 days of
      hospitalization. Ninety percent did not require rehospitalization. They
      experienced no complications. CONCLUSIONS: In only a minority of episodes can
      outpatient antibiotic management be implemented. Medical comorbidities and social
      barriers can make the transition to outpatient care difficult. However, initial
      hospitalization followed by oral antibiotic outpatient management appears safe
      and effective for low-risk patients who exhibit good responses to initial
      antibiotic therapy in hospital.

PMID- 16435378
TI  - Epstein-Barr virus associated hemophagocytic lymphohystiocytosis during
      maintenance treatment of acute lymphoblastic leukemia.

PMID- 16435379
TI  - Successful treatment of a child with t(15;19)-positive tumor.
AB  - A subset of poorly differentiated carcinomas is characterized by the
      translocation t(15;19)(q13;p13), resulting in a BRD4/NUT fusion gene. Typically,
      this tumor affects children or young adults, with a predilection for midline head
      and neck or thoracic structures. The clinical course is invariably fatal, in
      spite of intensive chemotherapy and radiotherapy. We here present the successful
      treatment of a 10-year-old boy who presented with a BRD4/NUT-positive
      undifferentiated tumor in the iliac bone. The patient was selected for combined
      modality therapy, and has remained in complete continuous remission for close to
      13 years. The findings show that t(15;19)-BRD4/NUT-positive tumors may arise in
      locations more typical for other pediatric tumors, such as Ewing sarcoma, and
      that they not always display epithelial differentiation. More importantly, our
      results also demonstrate that at least some patients with t(15;19)-positive
      tumors may be successfully treated.

PMID- 16435380
TI  - Topotecan by 21-day continuous infusion in children with relapsed or refractory
      solid tumors: a Children's Oncology Group study.
AB  - PURPOSE: The Children's Oncology Group conducted a phase II trial of 21-day
      continuous infusion topotecan to determine the response rate in pediatric
      patients with recurrent or refractory malignant solid tumors. PROCEDURE: Patients
      with Ewing sarcoma family of tumors (ESFT), osteosarcoma (OS), soft tissue
      sarcomas (STS), medulloblastoma (MB)/primitive neuroectodermal tumor (PNET),
      astrocytoma, or neuroblastoma (NB) recurrent or refractory to conventional
      therapy, measurable disease, and adequate organ function were treated with
      topotecan 0.3 mg/m2/day by continuous intravenous infusion for 21 consecutive
      days, followed by 7 days without therapy prior to response assessment. RESULTS:
      Fifty-five patients were enrolled; two were ineligible, two were removed from
      protocol therapy prior to evaluation for response, and one was inevaluable for
      response, leaving 53 and 50 patients evaluable for toxicity and response,
      respectively. Objective responses were seen in 2/20 patients with ESFT (both
      partial responses, 4 and 19 courses), 0/10 OS patients, and 0/12 STS patients.
      There were insufficient patients enrolled to determine the response rate for the
      MB/PNET, astrocytoma, and NB strata. The most common Grade 3 or 4 toxicities
      during the first course of therapy were thrombocytopenia (12/53), neutropenia
      (8/53), and fatigue (7/53). CONCLUSION: Intravenous topotecan by 21-day
      continuous infusion is tolerable in pediatric patients with recurrent or
      refractory solid tumors. Limited activity was seen in ESFT and further
      development of this topotecan schedule as a single agent is not warranted.

PMID- 16435381
TI  - Belief in home chemotherapy.

PMID- 16435382
TI  - Acquired immune cytopenias post-cardiac transplantation respond to rituximab.
AB  - Hematologic abnormalities following solid organ transplantation are infrequently
      autoimmune in origin. We present a series of autoimmune cytopenias developing as
      a late complication of pediatric cardiac transplantation. Autoimmune cytopenias
      represented include autoimmune hemolytic anemia, acquired Glanzmann
      thrombasthenia, and idiopathic thrombocytopenic purpura. Standard therapies were
      used in each patient without sustainable results. Eventually, each patient was
      treated with and responded to rituximab. In this report, we review these cases,
      propose potential mechanisms for development of autoimmune cytopenias, and
      discuss our experience with rituximab in managing refractory autoimmune
      cytopenias.

PMID- 16435383
TI  - Parental cancer: characteristics of parents as predictors for child functioning.
AB  - BACKGROUND: The vulnerability of children when a parent is diagnosed with cancer
      may depend on a variety of variables. The current study examined the impact of
      characteristics of 180 parents diagnosed with cancer, along with 145 spouses, on
      the prevalence of emotional and behavioral problems in children. METHODS: Ill
      parents provided information on sociodemographics and illness-related variables
      and on the prevalence of problems in children by using the Child Behavior
      Checklist (CBCL). Both parents completed the two subscales that measure physical
      functioning and mental health of the RAND-36. RESULTS: The family situation
      (single parents, no or few siblings, oldest child) was one of the most important
      predictors of reported problems in primary school children, whereas adolescents
      were reported as having more problems when parents experienced treatment
      complications. A decrease in ill parents' physical functioning affected primary
      school daughters and adolescents, and both age groups were affected by the mental
      health of ill parents. Problems of ill fathers did not have a different impact on
      children from those of ill mothers. Spouses' physical limitations were indicative
      for problems in primary school children, whereas a worsening parental mental
      health was indicative for problems in adolescents. CONCLUSIONS: Findings
      illustrated that parents' characteristics must be taken into account when
      assessing vulnerability of children in this situation. Which variables
      particularly heighten the risk for problems depend on children's ages.

PMID- 16435384
TI  - Genetic polymorphisms and haplotypes of DNA repair genes in childhood acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Polymorphisms of DNA repair genes can alter protein structure and may
      impair DNA repair capacity. Defects in repairing damaged DNA lead to genetic
      instability and carcinogenesis. This study was performed to evaluate the effect
      of the polymorphisms of DNA repair genes on risk of childhood acute lymphoblastic
      leukemia (ALL). PROCEDURES: We genotyped polymorphisms of X-ray repair cross
      complimenting group 1 (XRCC1) codon 194 (Arg to Trp), 280 (Arg to His) and 399
      (Arg to Gln), and xeroderma pigmentosum group D (XPD) codon 312 (Asp to Asn) and
      715 (Lys to Gln) in 108 children with ALL and 317 healthy controls using PCR-RFLP
      method. The allele, genotype, and haplotype frequencies of these polymorphisms
      were compared between cases and controls using Chi-square or Fisher's exact test.
      PHASE computer software was used to analyze estimated haplotypes of the XRCC1 and
      XPD polymorphisms. RESULTS: The frequency of XRCC1 194Trp allele in patients was
      significantly lower than that in controls (odds ratio (OR) 0.67; 95% confidence
      interval (CI), 0.47-0.97). Individuals with XRCC1 194 Trp/Trp genotype had a
      significantly reduced risk of ALL (OR 0.22; 95% CI, 0.05-0.96). The frequency of
      the XRCC1 haplotype B (194Trp-280Arg-399Arg) was significantly lower in children
      with ALL when compared to controls. The XRCC1 399Gln allele was associated with a
      significantly increased risk of ALL (OR 1.67; 95% CI, 1.20-2.33). The frequency
      of the XRCC1 haplotype C (194Arg-280Arg-399Gln) was significantly higher in
      patients. There was no difference of allele frequencies of the XRCC1 280 (Arg to
      His), XPD 312 (Asp to Asn), or XPD 715 (Lys to Gln) between cases and controls.
      CONCLUSION: The XRCC1 194Trp allele and haplotype B showed a protective effect
      against development of childhood ALL. In contrast, individuals with the XRCC1
      399Gln allele and haplotype C were associated with increased risk for this
      disease.

PMID- 16435385
TI  - Urokinase system expression in gastric carcinoma: prognostic impact in an
      independent patient series and first evidence of predictive value in preoperative
      biopsy and intestinal metaplasia specimens.
AB  - BACKGROUND: The prognostic relevance of urokinase-type plasminogen activator (u
      PA), u-PA receptor (u-PAR), and plasminogen activator inhibitor 1 (PAI-1) in
      gastric carcinoma was demonstrated in an independent patient series. To the
      authors' knowledge,the roles of these activators as predictors of aggressive
      phenotypes in preoperative biopsies, Helicobacter pylori infection, and
      intestinal metaplasia have to date not been investigated simultaneously in
      resected tumors. The objectives of the current study were 1) to demonstrate the
      prognostic relevance of u-PA, u-PAR, and PAI-1 in an independent series; 2) to
      evaluate u-PA system expression in preoperative biopsy specimens compared with
      resected tumors; and 3) to evaluate u-PA system expression in intestinal
      metaplasias and samples with H. pylori infection. METHODS: In 104 patients with
      gastric carcinoma (median follow-up, 68 mos), u-PA, u-PAR, and PAI-1 in tumors
      and metaplasias were evaluated immunohistochemically. Preoperative biopsies were
      evaluated in a subset of patients. Patients were screened for H. pylori (urease)
      and tumor cells in bone marrow (u-PAR/CK18). RESULTS: u-PA and PAI-1 were
      confirmed as independent prognostic parameters, and u-PAR was associated with a
      trend toward a poor prognosis. u-PA system tumor expression was found to be
      correlated significantly with u-PAR in disseminated tumor cells and H. pylori
      infected tumors, implicating a role of H. pylori in protease induction. There was
      a significant correlation noted between u-PA system staining between preoperative
      biopsies and the results in resected tumors. The expression of u-PAR and PAI-1 in
      intestinal metaplasias was found to be associated significantly with advanced
      tumor stage (depth of invasion; pathologic tumor status) and lymph node
      involvement (pathologic lymph node status) and was correlated significantly with
      u-PA system expression in tumors. CONCLUSIONS: To the author's know the current
      study is the first to date to demonstrate that u-PA system expression may serve
      as a predictor of risk in intestinal metaplasias and preoperative biopsies,
      implicating consequences for neoadjuvant therapy. The independent impact on
      recurrence and survival and a correlation with u-PAR-expression of minimal
      residual disease were identified in this independent series.

PMID- 16435386
TI  - Results of intensive chemotherapy in 998 patients age 65 years or older with
      acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive
      prognostic models for outcome.
AB  - BACKGROUND: Elderly patients (age > or = 65 years) with acute myeloid leukemia
      (AML) generally have a poor prognosis. AML-type therapy results are often derived
      from studies in younger patients and may not apply to elderly AML. Many
      investigators and oncologists advocate, at times, only supportive care or
      frontline single agents, Phase I-II studies, low-intensity regimens, or
      'targeted' therapies. However, baseline expectations for outcomes of elderly AML
      with 'standard' AML-type therapy are not well defined. The aim was to develop
      prognostic models for complete response (CR), induction (8-week) mortality, and
      survival rates in elderly AML, which would be used to advise oncologists and
      patients of expectations with standard AML type therapy, and to establish
      baseline therapy results against which novel strategies would be evaluated.
      METHODS: A total of 998 patients age > or = 65 years with AML or high-risk
      myelodysplastic syndrome (> 10% blasts) treated with intensive chemotherapy
      between 1980 and 2004 were analyzed. Univariate and multivariate analyses of
      prognostic factors associated with CR, induction (8-week) mortality, and survival
      used standard methods. RESULTS: The overall CR rate was 45% and induction
      mortality 29%. Multivariate analysis of prognostic factors identified consistent
      independent poor prognostic factors for CR, 8-week mortality, and survival. These
      included age > or = 75 years, unfavorable karyotypes (often complex), poor
      performance (3-4 ECOG [Eastern Cooperative Oncology Group]), longer duration of
      antecedent hematologic disorder, treatment outside the laminar airflow room, and
      abnormal organ functions. Patients could be divided into: 1) a favorable group
      (about 20% of patients) with expected CR rates above 60%, induction mortality
      rates of 10%, and 1-year survival rates above 50%; 2) an intermediate group
      (about 50-55% of patients) with expected CR rates of 50%, induction mortality
      rates of 30%, and 1-year survival rates of 30%; and 3) an unfavorable risk group
      (about 25-30% of patients) with expected CR rates of less than 20%, induction
      mortality rates above 50%, and 1-year survival rates of less than 10%.
      CONCLUSIONS: Prognostic models, based on standard readily available baseline
      characteristics, were developed for elderly patients with AML, which may assist
      in therapeutic and investigational decisions. These predictive models, based on a
      retrospective analysis, will require validation in independent study groups.

PMID- 16435387
TI  - Long-term follow-up results of the combination of topotecan and cytarabine and
      other intensive chemotherapy regimens in myelodysplastic syndrome.
AB  - BACKGROUND: Progressive or higher-risk myelodysplastic syndrome (MDS) is often
      treated with intensive chemotherapy regimens used for acute myelogenous leukemia
      (AML). Patients with MDS are often older and may have contraindications to
      anthracycline-based regimens. Topotecan-cytarabine regimens have shown
      encouraging results in higher-risk MDS. The aim of this study was to analyze the
      long-term results with topotecan-cytarabine versus other intensive chemotherapy
      regimens in higher-risk MDS. METHODS: Five hundred ten patients with higher-risk
      MDS treated with intensive chemotherapy were reviewed. Their median age was 63
      years; 82% had intermediate 2 or high-risk MDS; 32% had secondary MDS; 40% had
      chromosome 5 or 7 abnormalities. Therapy was: topotecan-cytarabine in 77;
      idarubicin-cytarabine regimens in 270; topotecan-cytarabine and cyclophosphamide
      in 67; fludarabine-cytarabine in 96. Univariate and multivariate analyses were
      conducted to evaluate the independent associations of different variables, and
      most important, the treatment regimen, with complete response, induction
      mortality, and survival. RESULTS: The overall complete response (CR) rate was
      55%, induction mortality 17%, and 5-year survival rate 8%. The 5-year survival
      rate was 11% for patients younger than 65 years old and 17% for patients with a
      normal karyotype. Among 82 patients younger than 65 years with a normal
      karyotype, the CR rate was 67%, 5-year survival rate 27%, and 5-year CR duration
      rate 33%. Topotecan-cytarabine regimens were equivalent to idarubicin-cytarabine
      regimens in relation to CR rates and survival rates, but were associated with a
      lower induction mortality. Multivariate analysis confirmed that treatment
      regimens were not associated with independent significant differences in CR rates
      or survival. However, topotecan-cytarabine regimens were still selected to be
      associated with lower induction mortality rates. CONCLUSIONS: This analysis
      suggests that topotecan-cytarabine regimens are equally effective to other AML
      regimens in higher-risk MDS and may be less toxic. Topotecan-cytarabine may be
      considered a reasonable alternative to idarubicin-cytarabine in higher-risk MDS,
      particularly in older patients with contraindications to anthracyclines.

PMID- 16435388
TI  - Landmark trials in endocrine adjuvant therapy for breast carcinoma.
AB  - The review summarizes the outcomes of several landmark trials involving aromatase
      inhibitors that helped formulate current therapeutic approaches recommended by
      the American Society of Clinical Oncology for breast carcinoma treatment.

PMID- 16435389
TI  - Acetoacetate protects neuronal cells from oxidative glutamate toxicity.
AB  - Glutamate cytotoxicity contributes to neuronal degeneration in many central
      nervous system (CNS) diseases, such as epilepsy and ischemia. We previously
      reported that a high-fat and low-carbohydrate diet, the ketogenic diet (KD),
      protects against kainic acid-induced hippocampal cell death in mice. We
      hypothesized based on these findings that ketosis resulting from KD might inhibit
      glutamate cytotoxicity, resulting in inhibition of hippocampal neuronal cell
      death. Therefore, we investigated the role of ketone bodies [acetoacetate (AA)
      and beta-hydroxybutyrate (beta-OHB)] both in a mouse hippocampal cell line (HT22)
      and in rat primary hippocampal neurons. As a result, we found that pretreatment
      with 5 mM lithium AA and 4 mM Na beta-OHB protected the HT22 hippocampal cell
      line and primary hippocampal neuronal culture against 5 mM glutamate toxicity and
      that up to 2 hr of pretreatment with 5 mM AA had a protective effect against 5 mM
      glutamate toxicity in the HT22 cell line. Pretreatment with 5 mM AA decreased ROS
      production of HT22 cell line at 2 and 8 hr exposure of glutamate, and it
      decreased the appearance of annexin V-positive HT22 cells, which are indicative
      of an early stage of apoptosis, and propidium iodide-positive HT22 cells, which
      are indicative of necrosis.

PMID- 16435390
TI  - Sensory neurite outgrowth on white matter astrocytes is influenced by
      intracellular and extracellular S100A4 protein.
AB  - The central nervous system (CNS) is considered a nonpermissive environment for
      axonal regeneration because of the presence of myelin and associated repulsive
      molecules. However, neural cells transplanted to the CNS preferably migrate and
      extend their fibers in white matter areas. We previously showed that white matter
      astrocytes in vivo express the calcium-binding protein S100A4, which is strongly
      up-regulated in areas of white matter degeneration. To investigate the role of
      white matter astrocytes and their specific protein S100A4 in axonal regeneration,
      we developed white matter astrocyte cultures with strong S100A4 expression and
      grew dissociated adult dorsal root ganglion (DRG) cells on top of astrocytes for
      24 hr. By using small interfering S100A4 RNA, we were able to eliminate S100A4
      expression and compare growth of DRG cell neurites on S100A4-silenced and S100A4
      expressing astrocytes. In addition, we studied whether extracellular S100A4 has
      an effect on neurite growth from adult DRG cells cultured on S100A4-expressing
      white matter astrocytes. Our data show that white matter astrocytes are
      permissive for neurite growth, although high levels of S100A4 in white matter
      astrocytes have a negative effect on this growth. Extracellular application of
      S100A4 induced extensive growth of DRG cell neurites on white matter astrocytes.
      These findings suggest that white matter astrocytes are able to support axonal
      regeneration and, furthermore, that administration of extracellular S100A4
      provides strong additional support for axonal regeneration.

PMID- 16435391
TI  - Expression of myelin basic protein in two oligodendroglial cell lines is
      modulated by apotransferrin through different transcription factors.
AB  - We have shown that apotransferrin (aTf) promotes the differentiation of two
      oligodendroglial cell (OLGc) lines, N19 and N20.1, representing different stages
      of OLGc maturation. Although in both cell lines aTf promoted myelin basic protein
      (MBP) expression, an increase in cAMP levels and CREB phosphorylation was
      observed only in the less mature cells (N19), suggesting that the maturation
      induced by aTf is achieved probably through different signaling pathways. We
      transfected both cell lines with the proximal region of the human MBP promoter
      fused to the lacZ reporter gene. In both transfected cell lines, addition of aTf
      produced an activation of the promoter. To elucidate the mechanisms involved in
      this action, Western blot analysis, EMSAs, and RT-PCR were performed for
      different transcription factors involved in mbp regulation. In the N20.1 line,
      treatment with aTf increased the expression and the DNA-binding capacity of
      thyroid hormone (TH) receptors, Sp1, and nuclear factor-kappaB (NFkappaB). For
      these cells we found that an inductor of NFkappaB (tumor necrosis factor-alpha)
      promoted MBP messenger synthesis, whereas mithramycin, a specific inibitor of
      Sp1, and a cAMP analog (db-cAMP) inhibited its transcription. In the N19 cell
      line, aTf stimulated NF-I and NFkappaB activation, but, aside from aTf, only db
      cAMP induced mbp transcription. These data suggest that, depending on the OLGc
      maturational stage, aTf modulates MBP expression and OLGc differentiation through
      different signaling pathways and different transcription factors.

PMID- 16435392
TI  - Erythropoietin preconditioning in neuronal cultures: signaling, protection from
      in vitro ischemia, and proteomic analysis.
AB  - In this study we confirmed the presence of the erythropoietin (EPO) receptor on
      both cultured cortical neurons and PC12 cells and showed that EPO can induce
      changes in p38, ERK, and JNK signaling molecules in these cells. We induced EPO
      preconditioning in cortical neuronal cultures that protected neurons from a
      subsequent in vitro ischemic insult (transient oxygen-glucose deprivation). To
      investigate downstream changes in protein expression in EPO-preconditioned
      cortical neuronal cultures, we used two-dimensional gel electrophoresis. Overall,
      EPO preconditioning resulted in protein up-regulation, and, from 84 of the most
      differentially expressed proteins selected for identification, the proteins or
      tentative proteins were identified in 57 cases, representing 40 different
      proteins. Different protein spots representing the same or closely related
      protein(s) occurred for 13 of the identified proteins and are likely to represent
      posttranslational modifications or proteolytic fragments of the protein. Two
      proteins (78-kD glucose-regulated protein and tropomyosin, fibroblast isoform 1)
      were detected in control neuronal cultures, but not following EPO preconditioning
      treatment, whereas one protein (40S ribosomal protein SA) was detected only
      following EPO preconditioning. Most of the other proteins identified had not
      previously been associated with EPO preconditioning and will aid in the
      understanding of EPO's neuroprotective response and possibly the development of
      new therapeutic interventions to inhibit neuronal death in acute and chronic
      neurodegenerative diseases.

PMID- 16435393
TI  - Activation of NF-kappaB transcription factor in the preterm ovine brain and
      placenta after acute LPS exposure.
AB  - Intrauterine infection may be causally related to inflammation and injury of the
      fetal brain, however the mechanisms by which this occurs are unclear. We have
      investigated whether nuclear factor (NF)-kappaB, a transcription factor for
      proinflammatory cytokines, is activated in the fetal brain after acute LPS
      exposure. At 95 days of gestation (term = approximately 147 days), 5 fetuses
      received a single intravenous bolus dose of LPS (1 microg/kg); 6 fetuses served
      as controls. Fetal blood samples were taken hourly for 6 hr post LPS-exposure to
      assess physiological status. Ewes and fetuses were then euthanased, placental and
      brain tissue examined histologically, and NF-kappaB activation assessed in
      several regions of the fetal brain using an electromobility shift assay (EMSA).
      Oxidative stress was measured using lipid peroxidation and 8-isoprostane
      biochemical assays and brain cytokine concentrations analysed by enzyme linked
      immunosorbent assay (ELISA). LPS-exposed fetuses (relative to controls) were
      hypoxemic and the haematocrit and lactate levels had increased. In the brains of
      LPS-exposed fetuses compared to controls, NF-kappaB binding activity was elevated
      in the hippocampus and the thalamus/basal ganglia; 8-isoprostane levels were
      elevated overall (P < 0.05) in the parietal/occipital/temporal lobes and
      thalamus/basal ganglia. TNF-alpha and IL-6 concentrations were not elevated,
      however, there was a tendency for an elevation of IFN-gamma concentrations in the
      thalamus/basal ganglia. IFN-gamma concentration was elevated (P < 0.05) in the
      plasma 4 hr after LPS-exposure. In the placenta, NF-kappaB binding activity was
      increased (P < 0.05). We conclude that acute systemic administration of LPS leads
      to increased binding activity of NF-kappaB subunits in specific regions of the
      fetal brain and in the placenta, but that there is no clear-cut relationship
      between this elevation and vulnerability to endotoxic damage.

PMID- 16435394
TI  - Glutamate release by neurons evokes a purinergic inhibitory mechanism of osmotic
      glial cell swelling in the rat retina: activation by neuropeptide Y.
AB  - Glial cell swelling is a central cause of ischemic edema in the brain and retina;
      however, the regulation of glial cell volume by endogenous factors in situ is
      largely unknown. In slices of the postischemic retina of the rat, the somata of
      glial (Muller) cells swell upon hypotonic stress that is not observed in slices
      of control retinas. We describe an endogenous signaling pathway that leads to
      inhibition of the osmotic glial cell swelling, and that is evoked by the release
      of glutamate from retinal neurons upon application of neuropeptide Y. Glutamate
      activates metabotropic glutamate receptors on swollen glial cells, which evokes a
      Ca2+ -independent purinergic signaling cascade that involves release of ATP, P2Y1
      receptor activation, and transporter-mediated release of adenosine. Activation of
      A1 receptors causes the inhibition of osmotic glial cell swelling, by a protein
      kinase A-dependent activation of K+ and Cl- channels. It is proposed that the
      glutamate-evoked purinergic receptor signaling of glial cells is crucially
      involved in the cell volume homeostasis of the retina, and that this mechanism
      may contribute to the protective effect of adenosine in the ischemic tissue.

PMID- 16435395
TI  - Effects of 8-OH-DPAT on hippocampal NADH fluorescence in vivo in anaesthetized
      rats.
AB  - Systemic administration of the 5-HT1A receptor agonist 8-OH-DPAT modifies 5-HT
      neuronal transmission via stimulation of presynaptic and postsynaptic receptors.
      Compared to the effects of presynaptic receptor stimulation, there are less data
      on the effects of postsynaptic 5-HT1A receptors and the net effects of a
      stimulation of pre- and postsynaptic 5-HT1A receptors available. We measured the
      neuronal activity in the rat hippocampus after systemic treatment with 8-OH-DPAT
      in doses (30-300 microg/kg) known to reduce 5-HT release and anxiety-like
      behavior in rodents. Neuronal activity was assessed by laser-induced fluorescence
      spectroscopy determining changes in nicotinamide adenine dinucleotide (NADH)
      fluorescence in the ventral hippocampus of anaesthetized rats in vivo. NADH, a co
      substrate for energy transfer in the respiratory chain, mirrors mitochondrial
      activity. Increased NADH fluorescence signals lower consumption of NADH caused by
      neuronal inhibition. 8-OH-DPAT in a dose of 300 microg/kg, but not 100 microg/kg
      and 30 microg/kg, increased NADH fluorescence by maximal +27 +/- 3.5%, suggesting
      a decreased neuronal activity in the ventral hippocampus. The selective 5-HT1A
      antagonist WAY-100635 (3 mg/kg) prevented the increased NADH fluorescence after 8
      OH-DPAT, but had no own effect. The results show that systemic administration of
      the 5-HT1A agonist 8-OH-DPAT dose-dependently affects neuronal activity in the
      ventral hippocampus. The dose of 300 microg/kg seemingly activates presynaptic
      and postsynaptic receptors with dominating inhibitory postsynaptic effects.

PMID- 16435396
TI  - Neurogenic potential of human umbilical cord blood: neural-like stem cells depend
      on previous long-term culture conditions.
AB  - In vitro studies conducted by our research group documented that neural
      progenitor cells can be selected from human umbilical cord blood (HUCB-NPs). Due
      to further expansion of these cells we have established the first human umbilical
      cord blood-derived neural-like stem cell line (HUCB-NSC) growing in serum-free
      (SF) or low-serum (LS) medium for over 3 years. The purpose of the study was to
      evaluate the neurogenic potential of HUCB-NSCs cultured in SF and LS condition in
      different in vitro settings before transplantation. We have shown that the number
      of cells attaining neuronal features was significantly higher for cultures
      expanded in LS than in SF condition. Moreover, the presence of neuromorphogens,
      cultured rat astrocytes or hippocampal slices promoted further differentiation of
      HUCB-NSCs into neural lineage much more effectively when the cells had derived
      from LS cultures. The highest response was observed in the case of co-cultures
      with rat primary astrocytes as well as hippocampal organotypic slices. However,
      the LS cells co-cultured with hippocampal slices expressed exclusively a set of
      early and late neuronal markers whereas no detection of cells with glial-specific
      markers was possible. In conclusion, certain level of stem/progenitor cell
      commitment is important for optimal response of HUCB-NSC on the neurogenic
      signals provided by surrounding environment in vitro.

PMID- 16435397
TI  - Stability of sludge flocs under shear conditions: roles of extracellular
      polymeric substances (EPS).
AB  - The roles of extracellular polymer substances (EPS) in the shear stability of
      aerobic and anaerobic flocs were investigated. Both pH and EDTA concentration had
      a significant effect on the floc stability. The sludge flocs became much weaker
      as the solution pH increase to above 10. Addition of 1 mM EDTA or more could
      cause considerable cell erosion and deflocculation of the anaerobic flocs,
      whereas more than 3 mM EDTA was needed to show its adverse effect on the
      stability of aerobic flocs. A fraction of the EPS, around 10 mg/g SS for the
      aerobic flocs and 15 mg/g SS for the anaerobic flocs, could be extracted by fluid
      shear when the dispersed mass concentration approached the equilibrium. This
      suggests that most of the dispersed particles were glued by a small amount of
      readily-extractable EPS fraction. In addition to the abundance of this EPS
      fraction, its proteins/carbohydrates ratio, about 0.22:1 for the aerobic flocs
      and 2.66:1 for the anaerobic flocs, also appeared to be an important factor
      governing the microbial floc stability. A lower content of the readily
      extractable EPS fraction and a lower ratio of proteins/carbohydrates were
      responsible for the greater stability of microbial flocs. The total content of
      the EPS, however, did not show a direct correlation with the floc stability. A
      hypothesis about biological flocs with two distinct structural regions was
      proposed. The outer part contained dispersible cells loosely entangled by the
      readily-extractable EPS fraction. This part was layered and would become
      completely dispersed at an infinite shear intensity. On the other hand, the inner
      part contains biomass in a stable structure tightly glued by EPS, which could not
      be dispersed by shear except under unfavorable conditions.

PMID- 16435398
TI  - Integrated bioprocess for the production and isolation of urokinase from animal
      cell culture using supermacroporous cryogel matrices.
AB  - An integrated cell cultivation and protein product separation process was
      developed using a new type of supermacroporous polyacrylamide gel, called cryogel
      (pAAm-cryogel) support matrix. Human fibrosarcoma HT1080 and human colon cancer
      HCT116 cell lines were used to secrete urokinase (an enzyme of immense
      therapeutic utility) into the culture medium. The secreted protein was isolated
      from the circulating medium using a chromatographic capture column. A pAAm
      cryogel support with covalently coupled gelatin (gelatin-pAAm cryogel) was used
      for the cultivation of anchorage dependent cells in the continuous cell culture
      mode in 5% carbon dioxide atmosphere. The cells were attached to the matrix
      within 4-6 h of inoculation and grew as a tissue sheet inside the cryogel matrix.
      Continuous urokinase secretion into the circulating medium was monitored as a
      parameter of growth and viability of cells inside the bioreactor. No
      morphological changes were observed in the cells eluted from the gelatin-cryogel
      support and re-cultured in T-flask. The gelatin-pAAm cryogel bioreactor was
      further connected to a pAAm cryogel column carrying Cu(II)-iminodiacetic acid
      (Cu(II)-IDA)-ligands (Cu(II)-IDA-pAAm cryogel), which had been optimized for the
      capture of urokinase from the conditioned medium of the cell lines. Thus an
      automated system was built, which integrated the features of a hollow fiber
      reactor with a chromatographic protein separation system. The urokinase was
      continuously captured by the Cu(II)-IDA-pAAm cryogel column and periodically
      recovered through elution cycles. The urokinase activity increased from 250 PU/mg
      in the culture fluid to 2,310 PU/mg after recovery from the capture column which
      gave about ninefold purification of the enzyme. Increased productivity was
      achieved by operating integrated bioreactor system continuously for 32 days under
      product inhibition free conditions during which no backpressure or culture
      contamination was observed. A total 152,600 Plough units of urokinase activity
      was recovered from 500 mL culture medium using 38 capture columns over a period
      of 32 days.

PMID- 16435399
TI  - Competition between oxygen and nitrate respirations in continuous culture of
      Pseudomonas aeruginosa performing aerobic denitrification.
AB  - Continuous culture of P. aeruginosa was conducted with nitrate-containing media
      under the dilution rates (D) of 0.026, 0.06, and 0.13/h and the dissolved oxygen
      concentrations (DO) of 0-2.2 mg/L. The bacterium performed simultaneous O(2) and
      nitrate respiration in all of the systems studied. For each D, the (apparent)
      cell yield from glucose (Y(X/S)) was lower at zero DO, but did not change
      substantially with non-zero DO. In non-zero DO systems, Y(X/S) increased with
      increasing D, and when fit with a model considering cell death, gave the
      following parameters: maximum cell yield Y(X/S) (m) = 0.49, maintenance
      coefficient M(S) = 0.029 (/h), and cell decay constant k(d) = 0.014/h. The same
      model failed to describe the behaviors of zero-DO systems, where neither glucose
      nor nitrate was limiting and the limiting factor(s) remained unknown. The cell
      yield from accepted electron (Y(X/e)) was however relatively constant in all
      systems, and the energy yield per electron accepted via denitrification was
      estimated at approximately 69% of that via O(2) respiration. A closer examination
      revealed that increasing DO enhanced O(2) respiration only at extremely low DO (
      <0.05 mg/L), beyond which the increasing DO only slightly increased its weak
      inhibition on denitrification. While O(2) was the preferred electron acceptor,
      the fraction of electrons accepted via denitrification increased with increasing
      D.

PMID- 16435400
TI  - Modulation of therapeutic antibody effector functions by glycosylation
      engineering: influence of Golgi enzyme localization domain and co-expression of
      heterologous beta1, 4-N-acetylglucosaminyltransferase III and Golgi alpha
      mannosidase II.
AB  - The effector functions elicited by IgG antibodies strongly depend on the
      carbohydrate moiety linked to the Fc region of the protein. Therefore several
      approaches have been developed to rationally manipulate these glycans and improve
      the biological functions of the antibody. Overexpression of recombinant beta1,4-N
      acetylglucosaminyltransferase III (GnT-III) in production cell lines leads to
      antibodies enriched in bisected oligosaccharides. Moreover, GnT-III
      overexpression leads to increases in non-fucosylated and hybrid oligosaccharides.
      Such antibody glycovariants have increased antibody-dependent cellular
      cytotoxicity (ADCC). To explore a further variable besides overexpression of GnT
      III, we exchanged the localization domain of GnT-III with that of other Golgi
      resident enzymes. Our results indicate that chimeric GnT-III can compete even
      more efficiently against the endogenous core alpha1,6-fucosyltransferase
      (alpha1,6-FucT) and Golgi alpha-mannosidase II (ManII) leading to higher
      proportions of bisected non-fucosylated hybrid glycans ("Glyco-1" antibody). The
      co-expression of GnT-III and ManII led to a similar degree of non-fucosylation as
      that obtained for Glyco-1, but the majority of the oligosaccharides linked to
      this antibody ("Glyco-2") are of the complex type. These glycovariants feature
      strongly increased ADCC activity compared to the unmodified antibody, while Glyco
      1 (hybrid-rich) features reduced complement-dependent cytotoxicity (CDC) compared
      to Glyco-2 or unmodified antibody. We show that apart from GnT-III
      overexpression, engineering of GnT-III localization is a versatile tool to
      modulate the biological activities of antibodies relevant for their therapeutic
      application.

PMID- 16435401
TI  - Optimization of cyanophycin production in recombinant strains of Pseudomonas
      putida and Ralstonia eutropha employing elementary mode analysis and statistical
      experimental design.
AB  - Elementary mode analysis was applied to simulate conditions for cyanophycin (CGP)
      biosynthesis and to optimize its production in bacteria. The conclusions from
      these simulations were confirmed by experiments with recombinant strains of the
      wild types and polyhydroxyalkanoate (PHA)-negative mutants of Ralstonia eutropha
      and Pseudomonas putida expressing CGP synthetase genes (cphA) of Synechocystis
      sp. strain PCC6308 or Anabaena sp. strain PCC7120. In particular, the effects of
      suitable precursor substrates and of oxygen supply as well as of the capability
      to accumulate PHA in addition to CGP biosynthesis were investigated. Since CGP
      consists of the amino acids aspartate and arginine, the tricarboxylic acid cycle
      (TCC), which provides intermediates for biosynthesis of these amino acids, seems
      to be important. Excretion of intermediates of the TCC upon cultivation at
      restricted oxygen supply and conversion of fumarate mainly to malate and to only
      little succinate in the absence of oxygen indicated that TCC intermediates for
      arginine and aspartate biosynthesis were provided by the oxidative or reductive
      parts of the TCC, respectively. The following important conclusions were made
      from the experiments and the simulations: (i) external arginine additionally
      supplied to the medium, (ii) oxygen limitation, and (iii) absence of PHA
      accumulation exerted positive effects on CGP accumulation. These conclusions were
      utilized to obtain CGP contents in the cells of as high as 17.9% (w x w(-1))
      during cultivation of the investigated bacteria at the 30-L scale using mineral
      salts medium. Such high CGP contents were previously not obtained with these
      bacteria at a 30-L scale, even if complex media were used.

PMID- 16435402
TI  - Genotype and smoking history affect risk of levodopa-induced dyskinesias in
      Parkinson's disease.
AB  - Parkinson's disease (PD) patients vary widely in their response to levodopa
      treatment, and this variation may be partially genetic in origin. We determined
      whether particular dopamine and opioid receptor polymorphisms were associated
      with risk of earlier onset of dyskinesia side effects during levodopa therapy.
      Smoking status was also examined. The 92 subjects were recruited from the
      movement disorders clinic of a neurology practice associated with a medical
      school. All were adult-onset PD patients who had been taking levodopa at least 5
      years and/or had developed levodopa-induced dyskinesia. Carrying the G-allele of
      the A118G single nucleotide coding region polymorphism of the mu opioid receptor,
      as well as a history of never smoking, were independently associated with
      increased risk of earlier onset of dyskinesia (P=0.05 and 0.02, respectively).
      One genotype of the D2 dopamine receptor intronic dinucleotide repeat
      polymorphism (14 repeats/15 repeats, with frequency of 6%) was also associated
      with earlier dyskinesia (P=0.003). History of smoking has previously been
      associated with reduced risk of developing PD. Our results suggest that smoking
      history may also influence the response to levodopa, with contribution comparable
      to those of individual genes including the mu opioid receptor and D2 dopamine
      receptor.

PMID- 16435403
TI  - Words derived from the noun peptide.
AB  - Modifications of the noun peptide are explored and clarified; a few are
      condemned.

PMID- 16435404
TI  - Global. HIV infections doubled since 1995.

PMID- 16435405
TI  - Prison. Inmate's HIV medication denial claim dismissed.

PMID- 16435406
TI  - Transmission. Study details risk of HIV/AIDS infection at circuit parties.

PMID- 16435408
TI  - Disclosure. Court allows anonymous designation in defamation suit.

PMID- 16435407
TI  - SSI benefits denied HIV-positive man for lack of disability.

PMID- 16435409
TI  - Exposure. Jury convicts HIV-positive man of sexual assault.

PMID- 16435410
TI  - Putin urged to address "Russia's curse".

PMID- 16435411
TI  - Bangladeshis poisoned by arsenic sue British organisation.

PMID- 16435412
TI  - [70-year-old woman with depressive symptoms and personality change].
AB  - A seventy-year-old woman, formerly healthy and active, gradually changed and
      withdrew from social contact. She was admitted to a psychogeriatric ward with
      depressive symptoms, delusions and change of personality. We treated the
      condition as a depressive psychosis, but with little success. She was mentally
      rigid, withdrawn, behaved inappropriately and did not cooperate in the treatment.
      After months of gradual worsening we suspected frontotemporal dementia. Cognitive
      testing showed abnormal scores in tasks of executive functions but no major
      memory or language problems. Computerised tomography was negative. Single photon
      emission tomography (SPECT) showed marked hypoperfusion especially in the frontal
      lobes and with the lowest function on the left side. The investigations thus
      supported the diagnosis. All medication was tapered and she moved to a dementia
      care unit in her community. The case illustrates some of the diagnostic
      challenges in psychogeriatric medicine. Early frontotemporal dementia may easily
      be mistaken for depression, especially when apathy and withdrawal is dominant
      (apathetic/pseudodepressive subtype) and not disinhibition and inappropriate
      behaviour (disinhibited subtype).

PMID- 16435413
TI  - [Frontotemporal lobar dementia].

PMID- 16435414
TI  - Radiation-induced transgenerational carcinogenesis.

PMID- 16435415
TI  - Codes of Practice by IRPCG and CEWG.

PMID- 16435416
TI  - KONTEC 2005.

PMID- 16435417
TI  - Third International Symposium, 'Chronic radiation exposure: biological and health
      effects.'.

PMID- 16435418
TI  - Emergency contraception: science and religion collide.

PMID- 16435419
TI  - Peer review: a castle built on sand or the bedrock of scientific publishing?

PMID- 16435420
TI  - Quiz page. Rupture of the left kidney.

PMID- 16435421
TI  - Pioneers in cardiology.

PMID- 16435422
TI  - Oral pathology quiz #49. Case number 2. Irritation fibroma.

PMID- 16435423
TI  - Oral pathology quiz #49. Case number 3. Odontogenic keratocyst.

PMID- 16435424
TI  - Safety update: a year after Vioxx.

PMID- 16435425
TI  - When is it time to treat bone loss?

PMID- 16435427
TI  - Getting shot: fac ts about the flu vaccine.

PMID- 16435426
TI  - New tests for heart disease.

PMID- 16435428
TI  - A patch for osteoarthritis relief.

PMID- 16435429
TI  - What are the pros and cons of a dental implant?

PMID- 16435430
TI  - Exercise and aging: can you walk away from Father Time?

PMID- 16435431
TI  - Cancer of the penis.

PMID- 16435432
TI  - Ejaculation frequency and prostate cancer.

PMID- 16435433
TI  - On call. I know you have expressed reservations about alternative therapy from
      time to time. I realize that it's a tricky issue for doctors, but I find the idea
      appealing. In particular, I'd like your opinion about chelation therapy. I'm a 68
      year-old diabetic with angina.

PMID- 16435434
TI  - Lung cancer in women. Is lung cancer different in women? Yes and no.

PMID- 16435435
TI  - Exercise sampler: building hip strength. "What weight-bearing exercises do you
      suggest for strengthening the hipbones?" asks a reader. Here are some
      suggestions.

PMID- 16435436
TI  - Genital herpes: common but misunderstood. Don't assume that genital herpes isn't
      your concern.

PMID- 16435437
TI  - By the way, doctor. I've heard that taking Fosamax for a long time causes the
      jawbone to deteriorate. Do you know anything about this?

PMID- 16435438
TI  - [National Congress in the diagnosis and treatment of upper digestive tract
      bleeding].

PMID- 16435439
TI  - [Study on the microsatellite instability in astrocytoma].

PMID- 16435440
TI  - Update: Influenza activity--United States, December 25-31, 2005.

PMID- 16435441
TI  - Update: Influenza activity--United States, January 1-7, 2006.

PMID- 16435442
TI  - [Neurologic complications following hematopoietic stem cell transplantation.
      Study of 14 patients].
AB  - BACKGROUND AND OBJECTIVE: The frequency and cause of neurologic complications
      (NC) following hematopoietic stem cell transplantation (HSCT) have changed over
      time. We have analyzed the NC in 185 consecutive patients who underwent HSCT in a
      period of 5 years in a single HSCT Unit. PATIENTS AND METHOD: 185 consecutive
      patients underwent HSCT (44 allogeneic) between February 2000 and March 2005 to
      treat hematologic malignancies. Most frequent diagnoses were multiple myeloma (41
      patients) and acute myeloblastic leukemia (n = 35). Demographic and clinical
      data, HSCT characteristics and procedure-related events with special attention to
      neurological findings were recorded. Imaging studies (magnetic resonance imaging
      and/or computerized tomography scan), cerebro-spinal fluid analyses and
      microbiological studies were performed in all patients developing NC. RESULTS:
      After a median follow-up of 27 months, 14 patients (7.5%) developed NC, 6 of them
      after an allogeneic HSCT. The most common conditioning regimen in these patients
      was BEAM (5/14); 6 patients submitted to allogenic-HSCT received methotrexate and
      cyclosporin as graft-versus-host disease prophylaxis, and intrathecal prophylaxis
      of relapse was administered to 3 patients. The median time to the appearance of a
      NC was 13 days from HSCT (range: -4 to + 135 days). Seizures (8 cases) and
      encephalopathy (n = 2) were the most frequent clinical manifestations. In 12
      cases the cause of the NC was related to drugs, there was one case of viral
      encephalitis and in the remaining case was caused by hemorrhage. Two patients
      died, one due to thrombotic thrombocytopenic purpura attributed to cyclosporin
      and the other due to viral encephalitis. CONCLUSIONS: In our series drug toxicity
      was the main cause of NC (particularly seizures) following HSCT. Our results
      contrast with previous studies in which infections, especially of fungal origin,
      were the main cause of NC. These changes over time should be taken into account
      during diagnostic procedures.

PMID- 16435443
TI  - [Dates and figures important to the nursing profession].

PMID- 16435444
TI  - "Broadband" proteomics  tackles TB.

PMID- 16435445
TI  - CPAS: a proteomics data management system for the masses.

PMID- 16435446
TI  - New tuberculosis therapy offers potential shorter treatment.

PMID- 16435447
TI  - Human health under threat from ecosystem degradation.

PMID- 16435448
TI  - Medical costs push millions of people into poverty across the globe.

PMID- 16435449
TI  - Apparent sialadenopathy of the sublingual glands after general anesthesia with
      placement of laryngeal mask airway.
AB  - Sialadenopathy, inflammation of the salivary glands, is a rare anesthetic
      complication. This case conference describes a patient who developed
      sialadenopathy of the sublingual glands after placement of a laryngeal mask
      airway during a brief surgical procedure. The patient's history is detailed, the
      surgical and anesthetic procedures are described, and a discussion follows, which
      describes the different causes of this inflammatory process. In the comment, the
      physiology of the salivary gland is described in detail.

PMID- 16435450
TI  - No bird flu risk for consumers from properly cooked poultry and eggs.

PMID- 16435451
TI  - The death of Herod the Great.

PMID- 16435452
TI  - The soul/boatman analogy in Aristotle's De Anima.

PMID- 16435453
TI  - Physiognomy in Apuleius Metamorphoses 2.2.

PMID- 16435454
TI  - Men's age at marriage and its consequences in the Roman family.

PMID- 16435455
TI  - Disease imagery in Catullus 76.17-26.

PMID- 16435456
TI  - Myrrh and unguents in the "Coma Berenices".

PMID- 16435457
TI  - The generation of monsters in Hesiod.

PMID- 16435458
TI  - Pliny "Naturalis Historia" 36.121 and the number of balnea in Early Augustan
      Rome.

PMID- 16435459
TI  - "Odyssey" 19.535-50: on the interpretation of dreams and signs in Homer.

PMID- 16435460
TI  - Natural fertility and family limitation in Roman marriage.

PMID- 16435461
TI  - Epicurus on sex, marriage, and children.

PMID- 16435462
TI  - The reproductive technology of the Pythagoreans.

PMID- 16435463
TI  - Wanted: a new ethics field for health policy analysis.
AB  - Ethics guidance and ethical frameworks are becoming more explicit and prevalent
      in health policy proposals. However, little attention has been given to
      evaluating their roles and impacts in the policy arena. Before this can be
      investigated, fundamental questions must be asked about the nature of ethics in
      relation to policy, and about the nexus of the fields of applied ethical analysis
      and health policy analysis. This paper examines the interdisciplinary stretch
      between bioethics and health policy analysis. In particular, it highlights areas
      of scholarship where a health policy ethics specialization--as distinctive from
      bioethics--might develop to address health policy concerns. If policy and ethics
      both ask the same question, that question is: "What is the good, and how do we
      achieve (create, protect, cultivate) it?" To answer this question, the new field
      of "health policy ethics" requires development. First, we should develop a full
      set of ethical principles and complementary ethical theories germane to public
      policy per se. Second, we must understand better how explicit attention to
      ethical concerns affects policy dynamics. Third, we require new policy and
      ethical analytic approaches that contribute to constructive (not obstructive)
      policy making. Finally, we need indicators of robust, high quality ethical
      analysis for the purpose public policy making.

PMID- 16435464
TI  - Accountability for reasonableness: opening the black box of process.
AB  - Norman Daniels' and James Sabin's theory of "accountability for reasonableness"
      (A4R) is a much discussed account of due process for decision-making on health
      care priority setting. Central to the theory is the acceptance that people may
      justifiably disagree on what reasons it is relevant to consider when priorities
      are made, but that there is a core set of reasons, that all centre on fairness,
      on which there will be no disagreement. A4R is designed as an institutional
      decision process which will ensure that only those reasons which everybody will
      agree are relevant and appropriate form part of decision-making. The argument
      which we will put forward in this paper questions whether it is a simple matter
      to delineate the core set of reasons and claims that it is a potential problem in
      A4R that it does not provide an indication of the exact content of this process.
      The paper first briefly outlines the content of A4R. It is argued that
      disagreement on what services should be high priorities cannot be resolved solely
      with a reference to "due process." In order to retain consistency over time,
      decision-makers are required to agree and articulate what reasons qualify as
      relevant and how conflicting reasons are to be balanced in the course of the
      process. The second and main part of the paper then considers how the reason of
      "solidarity" can be handled within the A4R framework, and it is shown that
      deciding whether solidarity should be admitted to the core set of allowable
      reasons is not a simple matter.

PMID- 16435465
TI  - Should people die a natural death?
AB  - In the article the concept of natural death as used in end-of-life decision
      contexts is explored. Reviewing some recent empirical studies on end-of-life
      decision-making, it is argued that the concept of natural death should not be
      used as an action-guiding concept in end-of-life decisions both for being too
      imprecise and descriptively open in its current use but mainly since it appears
      to be superfluous to the kind of considerations that are really at stake in these
      situations. Considerations in terms of the quality of life cost of the
      intervention in relation to the quality and length of life benefits of the same
      intervention. In referring to the concept of natural death we risk to blur these
      considerations and end up in difficult distinctions between what is a natural and
      non- or un-natural death, a distinction which it is argued is of no real moral
      interest.

PMID- 16435466
TI  - Palliative care and the QALY problem.
AB  - Practitioners of palliative care often argue for more resources to be provided by
      the state in order to lessen its reliance on charitable funding and to enable the
      services currently provided to some of those with terminal illnesses to be
      provided to all who would benefit from it. However, this is hard to justify on
      grounds of cost-effectiveness, since it is in the nature of palliative care that
      the benefits it brings to its patients are of short duration. In particular,
      palliative care fares badly under a policy of QALY-maximisation, since procedures
      which prevent premature death (provided the life is of reasonable quality) or
      improve quality of life for those with longer life expectancy will produce more
      QALYs. This paper examines various responses to this problem and argues that in
      order to justify increased resources for palliative care its advocates must
      reject the 'atomistic' view of the value of life implicit in the QALY approach in
      favour of a 'holistic' or 'narrative' account. This, however, has implications
      which advocates of palliative care may be reluctant to embrace.

PMID- 16435467
TI  - Looking for the meaning of dignity in the Bioethics Convention and the Cloning
      Protocol.
AB  - This paper is focused on the analysis of two documents (the Council of Europe's
      Bioethics Convention and the Additional Cloning Protocol) inasmuch as they refer
      to the relationship between human dignity and human genetic engineering. After
      presenting the stipulations of the abovementioned documents, I will review
      various proposed meanings of human dignity and will try to identify which of
      these seem to be at the core of their underlying assumptions. Is the concept of
      dignity proposed in the two documents coherent? Is it morally legitimate? Is it,
      as some might assume, of Kantian origin? Does it have any philosophical roots?

PMID- 16435468
TI  - Giving voice to health professionals' attitudes about their clinical service
      structures in theoretical context.
AB  - Within the context of structural theories this paper examines what health
      professionals say about their clinical service structures. We firstly trace
      various conceptual perspectives on clinical service structures, discussing
      multiple theoretical axes. These theories question whether clinical service
      structures represent either superficial or more profound changes in hospitals. We
      secondly explore which view is supported though a content analysis of the free
      text responses of 111 health professionals (44 doctors, 45 nurses and 22 allied
      health practitioners) about their clinical service structures in a questionnaire
      survey in two large hospitals that had implemented clinical service structures
      three years previously. Commentaries unfavourable toward clinical service
      structures were made by 47.7% of staff, favourable by 24.3%, mixed (both
      favourable and unfavourable) by 17.1% and non-evaluative statements were made by
      10.8%. The most frequent criticisms were inefficient organisation of change
      (27%), poor management (24.3%), lack of cooperation between staff (15.9%) and
      failure to empower health practitioners (13.5%). All professions made more
      negative than positive evaluations of their clinical service structures but the
      ratio was highest for doctors and lowest for allied health. Ranking of nurses'
      and allied health staffs' specific evaluations were similar but both differed
      significantly from doctors'. Unfavourable or negative comments predominated, and
      change appears more superficial and less profound than advocates of structural
      contributions hope. Four types of belief systems about clinical service
      structures are apparent. Some study participants are disposed toward the status
      quo; others toward restructuring; yet others are team oriented; and a final group
      is tribally oriented. The implication of this paper for managers is that more
      work is needed if clinical service structures are to realise the promise of more
      multi-disciplinarity and less fragmentation across professional groups. For
      scholars, the implication is that marrying different theoretical frames with
      empirical data can serve to produce fresh perspectives and perhaps new insights.

PMID- 16435470
TI  - Acute terminal ileitis--review of recent literature on the relationship to
      Crohn's disease.

PMID- 16435469
TI  - Managing risk: a taxonomy of error in health policy.
AB  - This paper discusses the current initiatives on error and adverse events within
      healthcare, with a particular focus on the NHS, within the context of health
      policy. One of the key features of the paper is the proposal for an emergent
      taxonomy of the medical error literature, developed from the ideologies and
      rationales that underpin their approaches. This taxonomy provides details of
      three categories--empiricists, organisational rationalists and reformers of
      professional culture--and these act as an organising framework for the
      exploration of the potential consequences of current policy on errors and adverse
      events. This discussion highlights the tension between optimising health outcomes
      for patients and managing the health system as effectively as possible. In
      particular, the inherent tension between explicit managerial formulations of risk
      and implicit risk management strategies associated with medical professionalism
      are considered.

PMID- 16435471
TI  - Ranitidine in the treatment of duodenal ulceration.
AB  - In a randomized, double-blind, endoscopically controlled clinical trial, 40
      patients with duodenal ulcer were treated with either ranitidine (320 mg/day) or
      cimetidine (800 mg/day) for 28 days. The rate of healing of the ulcers
      (ranitidine, 78%, cimetidine, 45%) did not differ significantly in the two
      treatment groups. In a subsequent 'open' study, ranitidine (150 mg twice daily)
      healed the ulcers of 79% of 19 patients treated for 28 days. Treatment with
      ranitidine was not associated with significant adverse reactions and had no
      lasting effect on gastric secretory capacity. Whereas basal levels of serum
      testosterone rose significantly during treatment with cimetidine, no such
      increase was observed during treatment with ranitidine. We conclude that
      ranitidine can effectively and safely heal duodenal ulcers.

PMID- 16435472
TI  - The effect of atropine on plasma gastric inhibitory polypeptide (GIP), serum
      insulin, and blood glucose after intraduodenal infusion of fat.
AB  - Six healthy men were studied with a 10-min intraduodenal infusion of 100 ml corn
      oil (66 g triglycerides) on 2 separate days. On one of the days 0.5 mg atropine
      sulfate was also given intravenously before start of the fat infusion, followed
      by 0.75 mg atropine sulfate infused during the first hour. On the day without
      atropine, plasma GIP and serum insulin increased significantly. The increases in
      plasma GIP and serum insulin were significantly attenuated by atropine. Blood
      glucose fell on both days, the fall being slightly delayed by atropine.

PMID- 16435473
TI  - Serotonin as an inhibitor of gastrin.
AB  - A dose of exogenous serotonin (0.1 mg/kg/min) previously described to cause
      maximal acid inhibition, was infused into six chronically awake dogs and
      significantly inhibited acid output. Integrated basal gastrin output was
      inhibited from a mean of 232.6 pg-min/ml to 31.6 pg-min/ml (p < 0.05) by
      serotonin infusion. Antral explantation significantly increased gastrin levels
      from a mean control level of 163 +/- 71.1 pg/ml to a mean of 991.0 +/- 663.4
      pg/ml (p < 0.05). These elevated gastrin levels were then not significantly
      inhibited by serotonin. The effect of serotonin on gastrin output has not
      previously been documented. Whereas acid inhibition was uniformly achieved,
      serotonin inhibited basal gastrin output (integrated gastrin output) but not a
      stimulated level of gastrin output. Serotonin may be an important
      'enterogastrone', and its release may play a role both in acid inhibition and in
      preventing ulcer disease.

PMID- 16435474
TI  - Cholinergic secretory and inhibitory mechanisms in canine pancreatic secretion.
AB  - Dose-response relationships for pancreatic stimulants and the interactions by
      atropine were studied in conscious gastric and duodenal fistula dogs. Secretin,
      caerulein, and bethanechol, the two latter against background secretin, induced
      similar maximal secretions of water and bicarbonate, and maximal protein outputs
      with the two latter were not different. Actions of atropine differed according to
      type and dose of stimulant, dose of atropine, and secretory variable studied. In
      the dose interval of 10-40 microg x kg(-1) x h(-1), atropine suppressed the
      secretin-stimulated water and bicarbonate, but these or lower doses enhanced the
      response to submaximal caerulein. The secretion after 200 microg x kg(-1) x h(-1)
      or less bethanechol was unaffected by atropine, but the suppressed response to
      higher bethanechol doses was reversed and enhanced. These findings are compatible
      with the presence of one ductal secretory process sensitive to cholinergic
      influence in three ways: one secretory, partly atropine-sensitive, required for
      submaximal secretin's optimal action; one secretory, stimulated by bethanechol,
      and atropine-resistant; and one inhibitory, atropine-sensitive, triggered by
      caerulein (and high doses of bethanechol). Atropine at low doses inhibited the
      protein output by bethanechol but enhanced the submaximal caerulein response,
      which again indicates the presence of an inhibitory atropine-sensitive
      cholinergic principle. It is proposed that pancreatic polypeptide may be the
      mediator of this inhibition and that vasoactive intestinal polypeptide could be
      the mediator of the atropine-resistant cholinergic stimulation of water and
      bicarbonate secretion.

PMID- 16435475
TI  - The human stomach after antrectomy. A study of the type of epithelium, occurrence
      of gastrin-producing cells, and basal serum gastrin.
AB  - A histological and immunohistological investigation was performed on biopsy
      specimens from ten patients 3 to 35 years after antrectomy, to study the type of
      epithelium and the possible occurrence of gastrin-producing cells (G cells) in
      the distal stump of the stomach remnant. The study showed that parietal cells
      were present in all patients, whereas G cells could not be demonstrated, although
      areas of pyloric-type epithelium (pseudopyloric metaplasia, were seen in eight.
      We conclude that the pyloric-type metaplasia, which occurs in the fundic mucosa
      after antrectomy, does not involve the G cells. It is suggested that the normal
      levels of fasting serum gastrin in these patients originate from outside the
      gastric mucosa, presumably from the duodenal bulb.

PMID- 16435476
TI  - Dopamine receptors do not influence beta2-sympathomimetic-mediated inhibition of
      gastric acid secretion in the dog.
AB  - The effect of dopamine blockade by haloperidol and metoclopramide on beta2
      adrenergic-induced changes of acid secretion and pulse rate was studied in
      conscious gastric fistula dogs. Neither haloperidol (0.15 mg/kg and 0.60 mg/kg)
      nor metoclopramide (0.25 mg/kg and 1.0 mg/kg), given intravenously, had a
      significant influence on beta2-adrenergic-induced inhibition of gastric acid
      secretion or tachycardia. Dopamine blockade had no influence on pentagastrin
      stimulated gastric acid secretion, but it increased pulse rate. It is concluded
      that dopamine receptors are not involved in the inhibiton of acid output or
      tachycardia induced by beta2-sympathomimetics, and dopamine is probably not a
      neurotransmitter for these effects.

PMID- 16435477
TI  - A clinical and socio-medical investigation of patients 5 years after surgical
      treatment for duodenal ulcer. I. Behavioural consequences and psychological
      symptoms.
AB  - Within the framework of the Aarhus County Vagotomy Trial a socio-medical
      interview investigation was performed. Ninety-one patients were asked to
      participate. Half of the patients had an ulcer history of more than 15 years. One
      fifth had experienced preoperative complications. Thirty-nine per cent of the
      patients showed changes in social activity according to Patrick's grading. Within
      work and leisure time significant improvements had taken place. Most of the
      patients with paid work were characterized by a high degree of satisfaction,
      conscientiousness, and stability at work. Symptoms indicating psychological
      impairment were commoner among the patients than in the background population. No
      accumulation of tobacco or alcohol abuse was found. The consumption of medicine
      was rather high. During the period of observation a decrease in the consumption
      of ulcer drugs, but not in other drugs, was noted. The frequency of sick days was
      rather high. The rate of consultations at the general practitioner did not differ
      from what would be expected. It is suggested that surgical cure of an ulcer only
      has some impact on the total life situation of the patients and that non-specific
      psychological symptoms in some patients may invalidate the overall result of
      treatment.

PMID- 16435478
TI  - A clinical and socio-medical investigation of patients 5 years after surgical
      treatment for duodenal ulcer. II. Association of social and psychological factors
      with surgical outcome.
AB  - Within the framework of the Aarhus County Vagotomy Trial a socio-medical
      investigation was performed. Eighty-eight patients were interviewed. Data were
      collected concerning the patients' own assessments and several psychological
      symptoms. The interview also comprised questions about education, career, and
      personal and family problems. The surgeon's assessment, expressed by the Visick
      classification, was significantly correlated with the patients' assessments. In
      the analysis of predictors for surgical failure expressed by the Visick
      classification, age was the only significant predictor. Indicators of social or
      psychological stress showed a tendency towards association with an unfavourable
      outcome. No associations were found between the selected predictors and surgical
      failure expressed as recurrent ulcer. Patients classified as Visick III or IV had
      an accumulation of non-specific psychological symptoms indicating psychological
      impairment. It is suggested that evaluations of surgical outcome for duodenal
      ulcer consider both a specific surgical dimension and a subjective dimension
      expressed by the patients' judgements and/or expression of their health status.

PMID- 16435479
TI  - On the role of intramural nerves in the pathogenesis of cholera toxin-induced
      intestinal secretion.
AB  - Intestinal secretion was produced in anesthetized cats and rats by exposing
      isolated intestinal segments to cholera enterotoxin. Giving, for example,
      tetrodotoxin, a nerve-conduction-blocking agent, or adding lidocaine, a local
      anesthetic agent, to the solution in the intestinal segments markedly inhibited
      the rate of choleraic secretion, and in most experiments a net absorption of
      fluid was observed. The results suggest that intramural nervous mechanisms are
      involved in the pathogenesis of choleraic secretion.

PMID- 16435480
TI  - Acetazolamide interferes with the protective effect of prostaglandin E2 in the
      rat gastric mucosa.
AB  - Oral prostaglandin E2 protected the gastric mucosa against the damage induced by
      intraperitoneal indomethacin in the rat. Blocking of the gastric alkaline
      secretion by subcutaneous acetazolamide potentiated the ulcerogenic action of
      indomethacin and reduced or abolished the protective effect of a submaximal dose
      prostaglandin E2. The results are compatible with the hypothesis that stimulation
      of the alkaline secretion is one of the mechanisms by which prostaglandin E2
      protects the gastric mucosa.

PMID- 16435481
TI  - Oxalate metabolism in man studied during total parenteral nutrition.
AB  - The mean urinary excretion of oxalate was 325 micromol/24 h in six patients
      during total parenteral nutrition (TPN). The urinary excretion of oxalate was
      considered to be equal to the endogenous oxalate production. A 2-day load of the
      oxalate precursor glycine given to five patients did not influence the oxalate
      excretion in spite of increased serum glycine concentrations. A 3-day load of the
      oxalate precursor ascorbic acid given to four patients increased the oxalate
      excretion in all patients. In one patient TPN was prolonged for 20 days without
      any change in the amount of oxalate excreted.

PMID- 16435482
TI  - Oxalate metabolism after intestinal bypass operations.
AB  - Hyperoxaluria and kidney stones are frequent following intestinal bypass
      operations. The urinary oxalate excretion was studied for 10-13 days during
      enteral and parenteral nutrition in six patients operated on because of massive
      obesity with a jejunoileostomy. The oxalate excretion in urine was higher than
      normal in all patients on normal diet. The excretion decreased on low-oxalate
      diet. Further decrease was observed during total parenteral nutrition (TPN). The
      oxalate excretion was stabilized at a low level within 48 h after the start of
      TPN and was unchanged during the rest of the study. This included a period of 2
      days when a load of the oxalate precursor glycine (10 and 20 g) was given
      parenterally to five patients, resulting in increased serum glycine
      concentration. A slight decrease in oxalate excretion was found when the amino
      acid part (Vamin with 10% glucose) of the TPN solution was given enterally
      instead of parenterally in two patients. This study has indicated that the main
      reason for hyperoxaluria in patients with intestinal bypass operations is
      hyperabsorption of dietary oxalate. It seems likely that these patients have a
      normal endogenous oxalate production.

PMID- 16435483
TI  - Enzymic esterification of cholesterol in rat intestinal mucosa catalyzed by acyl
      CoA: cholesterol acyltransferase.
AB  - Previous work has shown CoA-dependent esterification of cholesterol in rat
      intestinal mucosa. Using (1-(14)C)oleoyl-CoA as the labeled substrate, we have
      proved that the esterification is catalyzed by acyl-CoA: cholesterol
      acyltransferase (ACAT) existing in the 'microsomal fraction' of the mucosal cell.
      The apparent K(m) for oleoyl-CoA is 25 microM, the optimal pH 7.4-7.9, and the
      optimal concentration of albumin 10-20 mg/ml. The reaction is rectilinear for
      only 2 min. Increasing the microsomal cholesterol concentration by incubation
      with plasma from patients with familial lecithin: cholesterol acyltransferase
      deficiency leads to increasing ACAT activity. The ACAT was inhibited by
      taurocholate and by the thiol-blocking agent 5,5'-dithiobis(2-nitrobenzoic acid).
      The specific activity of the enzyme is high-that is, approximately 1 nmol
      cholesteryl oleate formed x mg microsomal protein(-1) x min(-1).

PMID- 16435484
TI  - GIP and insulin responses to oral glucose in coeliac patients before and after
      treatment.
AB  - The responses of plasma gastric inhibitory polypeptide (GIP) and insulin to oral
      glucose were studied in five patients with untreated coeliac disease. These
      patients were restudied after one year on a gluten-free diet. In the untreated
      patients, the blood glucose, serum insulin, and GIP levels were significantly
      lower than in the controls. After gluten withdrawal there was an improvement
      towards normality in the responses of blood glucose, serum insulin, and GIP. The
      results show that untreated coeliac disease is associated with abnormalities of
      intestinal and pancreatic hormone secretion and that these abnormalities are
      improved by gluten withdrawal.

PMID- 16435485
TI  - Depression of insulin release by anti-GIP serum after oral glucose in rats.
AB  - An oral glucose tolerance test (OGTT), an OGTT after infusion of anti-gastric
      inhibitory polypeptide (GIP) serum, and an intravenous glucose infusion were
      performed in unrestrained and unanesthetized rats. In the rats treated with anti
      GIP serum the insulin release was significantly depressed. This finding supports
      the concept that GIP is a physiologically important 'glucose-dependent insulin
      releasing peptide'.

PMID- 16435486
TI  - In vitro evidence of genetic heterogeneity within the heritable colon cancer
      syndromes with polyposis coli.
AB  - Assays of in vitro biological properties associated with cellular transformation
      revealed differences in cultured skin cells within the heritable colon cancer
      syndromes with polyposis coli. Such evidence suggested that genetic
      heterogeneity, long assumed from in vivo differences in extracolonic lesions in
      these syndromes, could be detected in vitro. None of the properties studied nor
      any grouping of them made identification of a specific genotype possible.

PMID- 16435487
TI  - Infusion of vasoactive intestinal polypeptide in man: pharmacokinetics and effect
      on gastric acid secretion.
AB  - Elimination and effect on acid secretion of vasoactive intestinal polypeptide
      (VIP) were studied in six healthy volunteers. On a background infusion of
      pentagastrin, 100 ng/kg-h, VIP was administered as stepwise intravenous infusions
      in doses of 0.5, 0.9, and 2.7 micro/g/kg-h, each dose being give for 1 h. Mean
      plasma VIP concentrations rose from 5.7 pmol/l to 28, 106 and 336 pmol/l during
      the VIP infusions. No significant changes in acid secretion occurred during VIP
      infusion as compared to infusion of pentagastrin alone, and no duodeno-gastric
      reflux was registered. Serum gastrin concentrations were unaltered during VIP
      infusion. Elimination of VIP was bi-exponential with half-lives of 2 and 21 min,
      respectively. Metabolic clearance rate was 42 ml/kg-min and the estimated volume
      of distribution 135 ml/kg.

PMID- 16435488
TI  - Simultaneous small-intestinal reconstruction and gastric partitioning as
      treatment for complications after jejunoileal bypass for morbid obesity.
AB  - Three female patients aged 34-35 years, who underwent jejunoileal bypass 11, 5,
      and 3 years ago, respectively, developed renal tubular acidosis. Furthermore, one
      of the patients needed prednisone for seronegative polyarthritis that developed 2
      years after a revision of her jejunoileal bypass. Because of the possible risk of
      renal damage from renal tubular acidosis and to avoid recurrent obesity, the
      patients were offered a simultaneous intestinal reconstruction and gastric
      partitioning. This combined procedure promptly cured the renal tubular acidosis
      and the arthritis and simultaneously produced a maintained weight loss.

PMID- 16435489
TI  - Acid secretory potency and elimination of the 15-leucine gastrin-17 analogue in
      man.
AB  - The effect on gastric acid secretion and the elimination of a commercially
      available synthetic human gastrin analogue (15-Leucine Synthetic Human Gastrin I,
      15-LSG) were studied in six healthy human subjects. On a molar basis acid
      secretory efficacy was approximately four times greater than pentagastrin and
      secretory potency ten times greater. Elimination of 15-LSG was bi-exponential,
      with half-lives of 5.2 +/- 0.8 and 25.9 +/- 7.0 min. Metabolic clearance rate was
      6.9 +/- 0.4 ml/kg-min and volume of distribution 52 ml/kg.

PMID- 16435490
TI  - Continuous reaction time in patients with hepatic encephalopathy. A quantitative
      measure of changes in consciousness.
AB  - In 14 patients with encephalopathy due to cirrhosis of the liver levels of
      consciousness were assessed by clinical ratings and continuous reaction time
      measurements. The observations were compared with similar measurements made in
      patients with chronic brain syndrome, patients sedated with diazepam, and
      hospitalized controls. Patients with hepatic encephalopathy were characterized by
      having slower reaction times than patients from the other groups. Furthermore,
      the performance of several liver patients was decreasing during the test. This
      phenomenon was not seen in the other groups. The continuous reaction times in the
      liver patients were correlated with the clinical ratings, but the reaction times
      appeared to be more sensitive, since on several occasions this test became
      abnormal before the clinical rating. Patients dying within 3 months after the
      test had more abnormal reaction times than patients surviving this period,
      indicating a relation between this test and the severity of the liver disease.

PMID- 16435491
TI  - Turning up the heat.

PMID- 16435492
TI  - CPHVA defends health visitors in Scotland.

PMID- 16435493
TI  - Liam Byrne MP addresses the CPHVA.

PMID- 16435494
TI  - Connecting for health: a voice for community practitioners.

PMID- 16435495
TI  - Dying for dignity.

PMID- 16435496
TI  - The Parent Positive programme: opportunities for health visiting.
AB  - Health visitors have a key role in programmes that support and enhance parenting
      as part of their public health work. This paper reports the findings of an in
      depth study that explored how 12 purposefully sampled health visitors who had
      undergone training in the Parent Positive programme viewed their role after
      training and how they felt that it had influenced their practice. Participants
      reported that the training developed their communication skills, enabled them to
      make the links between public health and family focussed work, gave their role
      greater clarity and provided them with an opportunity to reflect on their
      practice with others. The paper identifies the implications for practice and the
      initial and continuing education of health visitors.

PMID- 16435497
TI  - Alzheimer's disease and the psychosocial burden for caregivers.
AB  - The majority of patients with Alzheimer's disease are cared for by their families
      at home. Caring for someone with Alzheimer's disease is commonly portrayed in
      terms of 'problematic' behaviour. This study explored the level of understanding
      carers have of the illness and the psychosocial impacts carers experience.
      Qualitative interviews were conducted with eight carers who had been looking
      after their relatives in community settings. Findings suggest that the carers in
      this study had a distinct lack of knowledge regarding Alzheimer's disease and its
      management. A number of psychosocial consequences of caring were identified,
      including: isolation; feelings of guilt; uncertainty regarding lack of knowledge;
      and loneliness. Carers failed to utilise available services appropriately, and
      thus gained little benefit from their presence. Carers perceived their
      experiences as 'problematic' and they suffered negative psychosocial effects due
      to their caring experiences. The findings suggest that carers require more
      information and explanation of their experiences. This would help them in their
      ability to cope with their spouses.

PMID- 16435498
TI  - Public health, health promotion and the health of people in prison.
AB  - Recent policy changes in England and Wales have transferred commissioning and
      funding of prison healthcare from the prison service to the National Health
      Service for the first time in its history. Most health services in prisons are
      now provided by primary care trusts (PCTs), with the consequence that PCTs have a
      new highly vulnerable population for whom health needs must be assessed and
      services provided. This article describes what is currently known about the
      health needs of prisoners and the subsequent implications for public health and
      health promotion. Following a brief discussion of national and international
      policy on health promotion in prisons, an overview is given of recent national
      and local initiatives on public health issues.

PMID- 16435499
TI  - Essential hypertension: recent changes in management.
AB  - This two-part series on essential hypertension highlights recent changes in the
      management of patients with sustained raised blood pressure (BP). A lower
      proportion of patients in Europe (5-12 per cent) compared with the USA (27 per
      cent) achieves optimum BP control, and strategies are needed to improve this
      discrepancy. This article focuses on the methods used to identify hypertension.

PMID- 16435500
TI  - Pay review in context.

PMID- 16435501
TI  - [Are the diagnosis and measurement of portal hypertension of interest?].

PMID- 16435502
TI  - Laparoscopic hepatic resection for hepatocellular carcinoma. Retrospective study
      of 12 patients.
AB  - AIMS: To assess the results of laparoscopic liver resection for hepatocellular
      carcinoma. PATIENTS AND METHODS: From 1998 to 2003, 12 laparoscopic liver
      resections for hepatocellular carcinoma were performed. RESULTS: There were no
      operative complications and no deaths. Conversion to laparotomy was required in
      one patient (8%) and transfusion in three patients (25%). One patient died of
      liver failure. Postoperative complications occurred in three patients (25%):
      trocar site bleeding, cardiac failure and biliary collection. The mean hospital
      stay was 5 days. No ascites and no transient liver failure occurred. During the
      mean follow up of 15 months the recurrence rate was 45.5%. No port site or
      peritoneal metastases were observed. Treatment of recurrence was second resection
      in two patients and microwave coagulation therapy in two other patients. Mean
      survival was 24 months. CONCLUSION: Laparoscopic liver resection is feasible in
      hepatocellular carcinoma if the tumor is unique, smaller than 5 centimeters and
      located in the left lateral segments or in the anterior or inferior segments of
      the right liver. Postoperative morbidity is low and long-term results seem to be
      similar to laparotomy.

PMID- 16435503
TI  - [Non-invasive diagnosis of portal hypertension in cirrhosis. Application to the
      primary prevention of varices].
AB  - One of the major complications of cirrhosis is the occurrence of portal
      hypertension and esophageal varices. At present, universal endoscopic screening
      of esophageal varices is recommended in association to primary prophylaxis in
      patients at high risk of variceal bleeding. But this screening is invasive and
      could be not cost-effective. Besides, pre-primary phrophylaxis is not effective
      and hampared by side effects. So, non invasive diagnosis of portal hypertension
      might be useful. This one could depend on non invasive measurement of hepatic
      venous pressure gradient, but its application to screening is not well-documented
      and its use in treatment monitoring is debated. A second way could be non
      invasive diagnosis of large esophageal varices because of prognostic and economic
      issues. Indirect echographic markers of portal hypertension and esophageal
      varices (ascites, portal vein diameter > or = 13 mm, spleen length, maximal and
      mean velocimetry of portal vein flow, respectively < 20 cm/s and < 12 cm/s) could
      be useful. Among this parameters, spleen length is an independent predictive
      marker of esophageal varices. Besides, several direct or indirect blood markers
      of fibrosis have been tested. Platelet count is repeatedly a predictive marker of
      esophageal varices in multivariate analysis. The other predictive factors of
      esophageal varices could be: prothrombin time, splenomegaly, spider naevi, Child
      Pugh class, bilirubinemia, platelet count/spleen diameter ratio and Fibrotest,
      but these data require validation. In summary, in regard to actual results, non
      invasive diagnosis of portal hypertension might be useful in esophageal varices
      screening, but the substitutes to endoscopy have limited place actually in
      clinical practice, and exclusive non invasive diagnosis of portal hypertension is
      not applicable; the only test that seems to be useful in clinical practice is
      conventional endoscopy awaiting the results of videocapsule.

PMID- 16435504
TI  - [Invasive diagnosis of portal hypertension in cirrhosis: a critical evaluation of
      the hepatic venous pressure gradient measurement].
AB  - Portal hypertension is defined by an increased pressure gradient between the
      portal vein and the inferior vena cava (N < 5 mmHg). The most commonly used
      technique to assess the severity of portal hypertension is the catheterization of
      one hepatic vein with measurement of pressures in a free position and in a wedged
      position using preferably a balloon catheter. The hepatic venous pressure
      gradient is calculated by the difference between both pressures. In most
      cirrhotic processes, venous pressure gradient gives a good evaluation of portal
      hypertension however, portal vein pressure can be higher than wedged hepatic
      venous pressure, particularly in presence of an increased pre-sinusoidal
      resistance. In such cases, a direct access to portal vein might be needed to
      assess the severity of portal hypertension. For an accurate interpretation of the
      hepatic venous pressure gradient, several strict criteria must be followed;
      otherwise the validity of measurements might be seriously questioned. Hepatic
      venous pressure gradient has been used as a prognostic marker of portal
      hypertension, particularly for the occurrence of bleeding from gastrophageal
      varices which almost never occur below a threshold value of 12 mmHg. However, the
      prognostic value of the hepatic venous pressure gradient for survival is still a
      controversial matter On the other hand, the use of hepatic venous pressure
      gradient has been proposed to monitor the pharmacological treatment of portal
      hypertension and it is generally accepted that reaching a same threshold value of
      12 mmHg should almost completely abolish the risk of first or recurrent variceal
      bleeding. A large number of studies have also reported that a 20% hepatic venous
      pressure gradient decrease should be considered as a significant response to
      therapy, the risk of the first or recurrent bleeding being significantly reduced
      in responders. But again there are conflicting results.

PMID- 16435505
TI  - [Carcinoid heart disease: an underestimated complication of endocrine digestive
      tumors].

PMID- 16435506
TI  - Gastrointestinal manifestations in severe scorpion envenomation.
AB  - OBJECTIVES: To evaluate the type and incidence of gastrointestinal manifestations
      secondary to scorpion envenomation and their prognostic significance. PATIENTS
      AND METHODS: All patients admitted to our ICU for scorpion envenomation were
      included in this retrospective chart review of a 13-year period (1990 - 2002).
      RESULTS: During the study period, 951 patients were admitted for scorpion
      envenomation and 72 (7.6%) died. Ages ranged from 0.5 to 90 years with a mean of
      14.7 +/- 17.4 years. Gastrointestinal symptoms were present in 700 patients
      (73.6%): nausea in 24 (2.5%), vomiting in 687 (72.2%) and diarrhea in 41 patients
      (4.3%). At univariate analysis, the presence of diarrhea was associated with a
      fatal outcome (P < 0.05). Diarrhea was also correlated with other indicators of
      severe envenomation and poor prognosis: respiratory failure (P = 0.01),
      neurological failure (P < 0.0001), liver failure (P < 0.0001) and low blood
      pressure requiring catecholamine support (P = 0.02). The multivariate analysis
      showed that young age (age less than 5 years), fever > 38.5 degrees C,
      neurological failure and pulmonary edema were independent factors of severity.
      Digestive disorders were more frequent in children and in this subgroup diarrhea
      appeared to be associated with poor outcome. In a subset of patients for whom
      data were available, fatal cases demonstrated significantly higher liver enzymes
      levels on admission. CONCLUSION: In Tunisia, gastrointestinal symptoms are often
      observed in severe scorpion envenomations, especially in young patients. In
      children, diarrhea and elevated liver enzymes are associated with poor prognosis.

PMID- 16435507
TI  - Gemcitabine combined with oxaliplatin is safe and effective in patients with
      previously untreated advanced pancreatic adenocarcinoma.
AB  - AIM: The aim of this study was to determine the safety and the efficacy of a
      gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients
      with metastatic or unresectable locally-advanced pancreatic cancer. PATIENTS AND
      METHODS: Patients received gemcitabine 1000 mg/m2 as a 10-mg/m2/min infusion on
      day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2-hour infusion, each cycle
      being given every 2 weeks. All patients had measurable disease and histological
      diagnosis before inclusion. Patients were treated until progression or for 12
      cycles in the absence of progression. Tumor lesions were assessed by computed
      tomography scan every 4 cycles. RESULTS: Between January 2001 and January 2003,
      32 patients were eligible for the study. The objective response rate (OR) was
      28.1% with a 12.5% complete response rate (CR). Median progression-free survival
      and median overall survival were 7 and 9 months, respectively. Median overall
      survival for patients with metastatic disease and locally-advanced disease were 7
      and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year
      (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32
      patients experienced a clinical benefit response. CONCLUSION: These results
      support the safety, the antitumor activity and the possibility of durable
      responses of the GEMOX regimen in patients with locally-advanced disease.

PMID- 16435508
TI  - Preoperative criteria of incomplete resectability of peritoneal carcinomatosis
      from non-appendiceal colorectal carcinoma.
AB  - OBJECTIVE: To analyse the causes of non resectability of peritoneal
      carcinomatosis (PC) of non-appendiceal colorectal carcinomas, discovered only at
      the time of the laparotomy. SUMMARY BACKGROUND DATA: The combination of a maximal
      cytoreductive surgery (resecting tumor deposits > 1 mm in diameter) with
      intraperitoneal chemohyperthermia results in cure a significant number of
      patients. Complete resection of the PC is the determining factor of this time
      consuming and resource-consuming therapy. Unfortunately, it has not been
      possible, so far, to safely predict complete resectability before carrying out
      the laparotomy. METHODS: All patients with colorectal PC who had undergone a
      laparotomy in order to receive this new treatment, but who finally presented a
      non completely resectable PC were included in our study. Their preoperative
      parameters were retrospectively studied and compared to matched number of
      patients who had successfully undergone this treatment. RESULTS: 29 patients had
      incomplete resection PC at laparotomy. They were compared with 29 matched
      patients who underwent a complete resection of the PC. The factors predicting non
      resectability were, in decreasing order of frequency: presence or persistence of
      an ascitis just before the laparotomy (P = 0.0008), progression of the PC while
      on neo-adjuvant chemotherapy (P = 0.01), abnormal CT- imaging (P = 0.03), and sub
      occlusive syndrome (P = 0.05). These parameters were partially inter-related.
      CONCLUSION: The persistence of ascitis and any progression of the disease while
      on chemotherapy are important predictive factors of incomplete resectability of
      non-appendiceal colorectal PC.

PMID- 16435509
TI  - [Management of colorectal cancer of elderly patients].

PMID- 16435510
TI  - [Use of genetics in the management of adenocarcinomas of the colon].

PMID- 16435511
TI  - [Hereditary non polyposis colon cancer: diagnosis and management].

PMID- 16435512
TI  - [Polyposis coli: a practical approach].

PMID- 16435513
TI  - [Chemotherapy and MSI status].

PMID- 16435514
TI  - [HNPCC syndrome].

PMID- 16435515
TI  - [Nodular regenerative hyperplasia following liver tuberculosis].
AB  - We reported a case of nodular regenerative hyperplasia revealed by hemorrhage
      from portal hypertention and ascites in a 81 years old patient. This patient
      presented two years ago hepatic tuberculosis well documented by liver biopsy. If
      this patient do not have exhaustive etiologic research of nodular regenerative
      hyperplasia, the relationship between the tuberculosis infection and the
      developpement of this nodular regenerative hyperplasia appears highly probable
      and must be researched.

PMID- 16435516
TI  - [Acute pancreatitis associated with hemophagocytic syndrome in systemic lupus
      erythematous: a case report].
AB  - Exceptionally, acute pancreatitis and reactive hemophagocytic syndrome (RHS) are
      observed in the course of systemic lupus erythematosus (SLE). However, the
      association of the two conditions has never been reported before. A 31-years-old
      woman with a 7-year history of SLE was admitted for abdominal pain and fever.
      Elevated serum amylase and pancreatic enlargement on computerized tomography
      confirmed the diagnosis of pancreatitis. Laboratory examinations revealed
      pancytopenia, abnormal hepatic tests, and elevation of serum LDH and triglyceride
      levels. Bone marrow aspiration showed hemophagocytosis. The patient responded
      well to high dose corticosteroids. About eighty cases of pancreatitis have been
      reported in patients with SLE. The mechanisms are still unclear: SLE as the
      primary etiologic factor, drug toxicity, especially steroids which play a
      controversial role, or infection. About 40 cases of RHS have been reported in
      patients with SLE, sometimes associated with active infection. Overall mortality
      is 38.5%. When RHS occurs as an initial manifestation of SLE, or in the course of
      active SLE, it responds well to immunosuppressive therapy.

PMID- 16435517
TI  - [Cytomegalovirus enterocolitis: a rare cause of gastrointestinal ischemia and
      bleeding].
AB  - Cytomegalovirus (CMV) infections are frequent in patients with severe
      immunodeficiency. We report a case of isolated digestive localization in a young
      woman initially non-immunocompromised. Initially, she was admitted in the
      intensive-care unit for a severe post-operative shock secondary to a respiratory
      distress syndrome. She then developed severe enterocolitis which was initially
      unexplained. Outcome was favorable but digestive perforations required multiple
      surgical digestive resections. The histological diagnosis was confirmed by
      immunofluorescence staining and the antigenemia and specific antibodies kinetics.
      We emphasize the various characteristics of this pathology and point out the risk
      of missing this unusual cause of digestive perforation and severe bleeding.

PMID- 16435518
TI  - [Duodenal migration of a mesenterico-caval prothesis].

PMID- 16435519
TI  - [Common bile duct obstruction by lymph node enlargment due to cat scratch
      disease].

PMID- 16435520
TI  - Isolated increased serum TSH response to TRH is prevalent in celiac disease and
      predicts poor response to treatment.

PMID- 16435521
TI  - [Hemorrhagic gastric metastasis of an ovarian carcinoma].

PMID- 16435522
TI  - [Digestive protein loss from an ileal multifocal stromal tumor].

PMID- 16435523
TI  - [Colonoscopic hepatitis C virus contamination: response of the SFED].

PMID- 16435524
TI  - [Should endoscopic examinations be programmed according to the patients' viral
      status?].

PMID- 16435525
TI  - What does sport have to do with AIDS?

PMID- 16435526
TI  - Burden: the phenomenon of mothering with HIV.
AB  - If most mothers continually struggle to comply with perceptions of the "good
      mother" in the face of fatigue, self-doubt, and overwhelming emotion, what must
      the experience be like for HIV-infected women with dependent children to live and
      to mother day-to-day with an increasingly chronic, but still fatal, disease? The
      purpose of this phenomenological study was to gain an understanding of the
      mothering and end-of-life issues faced by HIV-infected women with dependent
      children. Sixteen HIV-infected women reflecting diversity of ethnicity, age,
      number and ages of children, and health status were interviewed in depth. A
      phenomenon of mothering with HIV revealed a constitutive pattern of burden.
      Themes revealed were the burden of the diagnosis and health status, the burden of
      whether or not to reveal to children, the burden of an unknown future for
      themselves and their children, and relieving the burden of the diagnosis.

PMID- 16435527
TI  - Social network structure and social support in HIV-positive inner city mothers.
AB  - It has been documented that social support influences health outcomes of persons
      with chronic illnesses. The incidence of HIV and AIDS among minority women is
      growing at an alarming rate, but little is known about social support in this
      vulnerable population, and even less is known about the social network conveying
      that support. Guided by the convoy of social networks model, this study describes
      the social networks in a sample of HIV-positive, urban-dwelling mothers (N = 147)
      by stage of disease (i.e., asymptomatic, symptomatic, AIDS) and examines
      relationships between social network structure and social support. Hierarchical
      linear modeling showed that women's social networks were disproportionately
      populated by children, and network members of women with AIDS were significantly
      older than network members of HIV-positive women with or without symptoms.
      Profile analyses showed that women's perceptions of the quality of social support
      differed according to the proportion of family members populating different
      segments of the social network.

PMID- 16435528
TI  - Patterns of risk of depressive symptoms among HIV-positive women in the
      southeastern United States.
AB  - Depressive symptoms are a common response to HIV disease, and women appear to be
      at particularly high risk. The authors report results from a cross-sectional
      analysis of data collected from 280 rural women with HIV/AIDS in the Southeastern
      United States aimed at identifying risk factors of depressive symptoms. Stress
      theory provided a framework for identification of potential risk factors.
      Descriptive statistics, measures of association, and regression analyses were
      used to systematically identify patterns of risk. The final regression model
      included 22 factors that accounted for 69% of the variance in depressive
      symptoms. The majority of variance in depressive symptoms was accounted for by
      only six variables: the frequency of HIV symptoms, recent experiences of
      sadness/hopelessness, the availability of social support, and the use of three
      coping strategies: living positively with HIV, isolation/withdrawal, and
      denial/avoidance. The results suggest a number of intervention strategies for use
      with rural women with HIV/AIDS.

PMID- 16435529
TI  - Impact of support services provided by a community-based AIDS service
      organization on persons living with HIV/AIDS.
AB  - This study examined demographic, health-related, social support, and service
      utilization characteristics of clients with high and low use of a community-based
      AIDS service organization in Canada. The study confirmed that the organizations'
      services were reaching the most vulnerable persons living with HIV/AIDS. It found
      that a significantly greater number of high users compared with low users were
      single, lived alone, and reported poorer health. The similarity in functional
      health status and depression between user groups, despite high users' poorer
      health and greater social vulnerability, supports client reports that services
      have reduced client isolation and improved health-related quality of life.
      Finally, high users had lower expenditures for government-provided health and
      social services overall, particularly HIV specialists and AIDS medication, but
      significantly more expenditures for emergency room services and complementary
      therapies. The results suggest community-based services can enhance health
      related quality of life for persons living with HIV/AIDS by increasing providers'
      capacity to identify and address client depression and its consequences.

PMID- 16435530
TI  - Characteristics of people living with HIV who use community-based services in
      Ontario, Canada: implications for service providers.
AB  - Community-based AIDS service organizations (CBAOs) direct services to multiple
      needs people living with HIV/AIDS who are less likely to use mainstream health
      promotion services. As people live longer with HIV, the potential to enhance
      quality of life increases, yet little is known about who uses CBAOs or how this
      use affects other health and social services. This study of people living with
      AIDS in Ontario, Canada (n = 297) examined the demographic and health-related
      characteristics of people with AIDS who do and do not use CBAOs and their
      patterns of mainstream service utilization. It found that users of CBAOs were
      significantly less healthy, less able to sustain normal activities, and more
      often depressed. They reported physical disabilities significantly more often.
      Their quality of life was also lower along certain dimensions. They were
      significantly poorer and more reliant on government income supports. They
      consumed significantly more nonhospital health and social services and had
      significantly higher out-of-pocket costs. These results suggest CBAOs are being
      accessed appropriately by those most vulnerable. In an effort to strengthen CBAO
      capacity to recognize and address depression and physical health problems
      prevalent among their clients, links to other mainstream health promotion and
      social services is recommended.

PMID- 16435531
TI  - Cultural competence: what is needed in working with Native Americans with
      HIV/AIDS?

PMID- 16435532
TI  - Combining color and shape information for illumination-viewpoint invariant object
      recognition.
AB  - In this paper, we propose a new scheme that merges color- and shape-invariant
      information for object recognition. To obtain robustness against photometric
      changes, color-invariant derivatives are computed first. Color invariance is an
      important aspect of any object recognition scheme, as color changes considerably
      with the variation in illumination, object pose, and camera viewpoint. These
      color invariant derivatives are then used to obtain similarity invariant shape
      descriptors. Shape invariance is equally important as, under a change in camera
      viewpoint and object pose, the shape of a rigid object undergoes a perspective
      projection on the image plane. Then, the color and shape invariants are combined
      in a multidimensional color-shape context which is subsequently used as an index.
      As the indexing scheme makes use of a color-shape invariant context, it provides
      a high-discriminative information cue robust against varying imaging conditions.
      The matching function of the color-shape context allows for fast recognition,
      even in the presence of object occlusion and cluttering. From the experimental
      results, it is shown that the method recognizes rigid objects with high accuracy
      in 3-D complex scenes and is robust against changing illumination, camera
      viewpoint, object pose, and noise.

PMID- 16435533
TI  - Fingerprint multicast in secure video streaming.
AB  - Digital fingerprinting is an emerging technology to protect multimedia content
      from illegal redistribution, where each distributed copy is labeled with unique
      identification information. In video streaming, huge amount of data have to be
      transmitted to a large number of users under stringent latency constraints, so
      the bandwidth-efficient distribution of uniquely fingerprinted copies is crucial.
      This paper investigates the secure multicast of anticollusion fingerprinted video
      in streaming applications and analyzes their performance. We first propose a
      general fingerprint multicast scheme that can be used with most spread spectrum
      embedding-based multimedia fingerprinting systems. To further improve the
      bandwidth efficiency, we explore the special structure of the fingerprint design
      and propose a joint fingerprint design and distribution scheme. From our
      simulations, the two proposed schemes can reduce the bandwidth requirement by 48%
      to 87%, depending on the number of users, the characteristics of video sequences,
      and the network and computation constraints. We also show that under the
      constraint that all colluders have the same probability of detection, the
      embedded fingerprints in the two schemes have approximately the same collusion
      resistance. Finally, we propose a fingerprint drift compensation scheme to
      improve the quality of the reconstructed sequences at the decoder's side without
      introducing extra communication overhead.

PMID- 16435534
TI  - Error resilient pre/post-filtering for DCT-based block coding systems.
AB  - Block coding based on the discrete cosine transform (DCT) is very popular in
      image and video compression. Pre/post-filtering can be attached to a DCT-based
      block coding system to improve coding efficiency as well as to mitigate blocking
      artifacts. Previously designed pre/post-filters are optimized to maximize coding
      efficiency solely. For image and video communication over unreliable channels,
      those pre/post-filters are sensitive to transmission errors. This paper addresses
      the problem of designing pre/post-filters which are more error resilient.
      Reconstruction performance is measured by how low the average reconstruction
      error is, and how uniformly the reconstruction error is distributed. A family of
      pre/post-filters is designed to provide desired tradeoffs between coding
      efficiency and robustness to transmission errors. Experiments show that these
      filtering operators can achieve superior reconstruction performance without
      sacrificing much coding performance.

PMID- 16435535
TI  - Rate-distortion optimized hybrid error control for real-time packetized video
      transmission.
AB  - The problem of application-layer error control for real-time video transmission
      over packet lossy networks is commonly addressed via joint source-channel coding
      (JSCC), where source coding and forward error correction (FEC) are jointly
      designed to compensate for packet losses. In this paper, we consider hybrid
      application-layer error correction consisting of FEC and retransmissions. The
      study is carried out in an integrated joint source-channel coding (IJSCC)
      framework, where error resilient source coding, channel coding, and error
      concealment are jointly considered in order to achieve the best video delivery
      quality. We first show the advantage of the proposed IJSCC framework as compared
      to a sequential JSCC approach, where error resilient source coding and channel
      coding are not fully integrated. In the USCC framework, we also study the
      performance of different error control scenarios, such as pure FEC, pure
      retransmission, and their combination. Pure FEC and application layer
      retransmissions are shown to each achieve optimal results depending on the packet
      loss rates and the round-trip time. A hybrid of FEC and retransmissions is shown
      to outperform each component individually due to its greater flexibility.

PMID- 16435536
TI  - Optimized transmission of JPEG2000 streams over wireless channels.
AB  - The transmission of JPEG2000 images over wireless channels is examined using
      reorganization of the compressed images into error-resilient, product-coded
      streams. The product-code consists of Turbo-codes and Reed-Solomon codes which
      are optimized using an iterative process. The generation of the stream to be
      transmitted is performed directly using compressed JPEG2000 streams. The
      resulting scheme is tested for the transmission of compressed JPEG2000 images
      over wireless channels and is shown to outperform other algorithms which were
      recently proposed for the wireless transmission of images.

PMID- 16435537
TI  - Nonlinear image representation for efficient perceptual coding.
AB  - Image compression systems commonly operate by transforming the input signal into
      a new representation whose elements are independently quantized. The success of
      such a system depends on two properties of the representation. First, the coding
      rate is minimized only if the elements of the representation are statistically
      independent. Second, the perceived coding distortion is minimized only if the
      errors in a reconstructed image arising from quantization of the different
      elements of the representation are perceptually independent. We argue that linear
      transforms cannot achieve either of these goals and propose, instead, an adaptive
      nonlinear image representation in which each coefficient of a linear transform is
      divided by a weighted sum of coefficient amplitudes in a generalized
      neighborhood. We then show that the divisive operation greatly reduces both the
      statistical and the perceptual redundancy amongst representation elements. We
      develop an efficient method of inverting this transformation, and we demonstrate
      through simulations that the dual reduction in dependency can greatly improve the
      visual quality of compressed images.

PMID- 16435538
TI  - Variable-length lapped transforms with a combination of multiple synthesis filter
      banks for image coding.
AB  - A class of lapped transforms for image coding, which are characterized by
      variable-length synthesis filters, is introduced. In this class, the synthesis
      filter bank (FB) is first defined with an arbitrary combination of finite impulse
      response synthesis filters of perfect reconstruction FBs. An analysis FB is then
      obtained using direct matrix inversion or iterative implementation of Neumann
      series expansion. Moreover, to improve compression, we introduce a unitary
      transform that follows the analysis FB. This class enables a greater freedom of
      design than previously presented variable-length lapped transforms. We illustrate
      several design examples and present experimental results for image coding, which
      indicate that the proposed transforms are promising and comparable with
      conventional subband transforms including wavelets.

PMID- 16435539
TI  - A range/domain approximation error-based approach for fractal image compression.
AB  - Fractals can be an effective approach for several applications other than image
      coding and transmission: database indexing, texture mapping, and even pattern
      recognition problems such as writer authentication. However, fractal-based
      algorithms are strongly asymmetric because, in spite of the linearity of the
      decoding phase, the coding process is much more time consuming. Many different
      solutions have been proposed for this problem, but there is not yet a standard
      for fractal coding. This paper proposes a method to reduce the complexity of the
      image coding phase by classifying the blocks according to an approximation error
      measure. It is formally shown that postponing range?slash domain comparisons with
      respect to a preset block, it is possible to reduce drastically the amount of
      operations needed to encode each range. The proposed method has been compared
      with three other fractal coding methods, showing under which circumstances it
      performs better in terms of both bit rate and/or computing time.

PMID- 16435540
TI  - A fast and efficient hybrid fractal-wavelet image coder.
AB  - The excellent visual quality and compression rate of fractal image coding have
      limited applications due to exhaustive inherent encoding time. This paper
      presents a new fast and efficient image coder that applies the speed of the
      wavelet transform to the image quality of the fractal compression. Fast fractal
      encoding using Fisher's domain classification is applied to the lowpass subband
      of wavelet transformed image and a modified set partitioning in hierarchical
      trees (SPIHT) coding, on the remaining coefficients. Furthermore, image details
      and wavelet progressive transmission characteristics are maintained, no blocking
      effects from fractal techniques are introduced, and the encoding fidelity problem
      common in fractal-wavelet hybrid coders is solved. The proposed scheme promotes
      an average of 94% reduction in encoding-decoding time comparing to the pure
      accelerated Fractal coding results. The simulations also compare the results to
      the SPIHT wavelet coding. In both cases, the new scheme improves the subjective
      quality of pictures for high-medium-low bitrates.

PMID- 16435541
TI  - A 2-D orientation-adaptive prediction filter in lifting structures for image
      coding.
AB  - Lifting-style implementations of wavelets are widely used in image coders. A two
      dimensional (2-D) edge adaptive lifting structure, which is similar to Daubechies
      5/3 wavelet, is presented. The 2-D prediction filter predicts the value of the
      next polyphase component according to an edge orientation estimator of the image.
      Consequently, the prediction domain is allowed to rotate +/-45 degrees in regions
      with diagonal gradient. The gradient estimator is computationally inexpensive
      with additional costs of only six subtractions per lifting instruction, and no
      multiplications are required.

PMID- 16435542
TI  - Fast and efficient method for computing ART.
AB  - Angular radial transform (ART), which is the region-based shape descriptor of
      MPEG-7, has desirable properties for representing shape information in a small
      number of features with no redundancy. However, in order for ART to be useful,
      especially in limited computing environments, the computational cost of ART must
      be greatly reduced. In this paper, we derive symmetric/antisymmetric properties
      from the basis functions of ART and present a fast and efficient method to
      compute the ART coefficients using these properties. The proposed method
      significantly reduces the number of sinusoidal operations and multiplications in
      computing the coefficients of ART. Moreover, the memory requirements needed to
      store the ART basis functions in lookup tables are only 25% of the conventional
      method. The experimental results are presented to show the effectiveness of the
      proposed method.

PMID- 16435543
TI  - Robust photometric invariant features from the color tensor.
AB  - Luminance-based features are widely used as low-level input for computer vision
      applications, even when color data is available. The extension of feature
      detection to the color domain prevents information loss due to isoluminance and
      allows us to exploit the photometric information. To fully exploit the extra
      information in the color data, the vector nature of color data has to be taken
      into account and a sound framework is needed to combine feature and photometric
      invariance theory. In this paper, we focus on the structure tensor, or color
      tensor, which adequately handles the vector nature of color images. Further, we
      combine the features based on the color tensor with photometric invariant
      derivatives to arrive at photometric invariant features. We circumvent the
      drawback of unstable photometric invariants by deriving an uncertainty measure to
      accompany the photometric invariant derivatives. The uncertainty is incorporated
      in the color tensor, hereby allowing the computation of robust photometric
      invariant features. The combination of the photometric invariance theory and
      tensor-based features allows for detection of a variety of features such as
      photometric invariant edges, corners, optical flow, and curvature. The proposed
      features are tested for noise characteristics and robustness to photometric
      changes. Experiments show that the proposed features are robust to scene
      incidental events and that the proposed uncertainty measure improves the
      applicability of full invariants.

PMID- 16435544
TI  - Subsampling models and anti-alias filters for 3-D automultiscopic displays.
AB  - A new type of three-dimensional (3-D) display recently introduced on the market
      holds great promise for the future of 3-D visualization, communication, and
      entertainment. This so-called automultiscopic display can deliver multiple views
      without glasses, thus allowing a limited "look-around" (correct motion-parallax).
      Central to this technology is the process of multiplexing several views into a
      single viewable image. This multiplexing is a complex process involving irregular
      subsampling of the original views. If not preceded by low-pass filtering, it
      results in aliasing that leads to texture as well as depth distortions. In order
      to eliminate this aliasing, we propose to model the multiplexing process with
      lattices, find their parameters and then design optimal anti-alias filters. To
      this effect, we use multidimensional sampling theory and basic optimization
      tools. We derive optimal anti-alias filters for a specific automultiscopic
      monitor using three models: the orthogonal lattice, the nonorthogonal lattice,
      and the union of shifted lattices. In the first case, the resulting separable low
      pass filter offers significant aliasing reduction that is further improved by
      hexagonal-passband low-pass filter for the nonorthogonal lattice model. A more
      accurate model is obtained using union of shifted lattices, but due to the
      complex nature of repeated spectra, practical filters designed in this case offer
      no additional improvement. We also describe a practical method to design finite
      precision, low-complexity filters that can be implemented using modern graphics
      cards.

PMID- 16435545
TI  - Multiframe demosaicing and super-resolution of color images.
AB  - In the last two decades, two related categories of problems have been studied
      independently in image restoration literature: super-resolution and demosaicing.
      A closer look at these problems reveals the relation between them, and, as
      conventional color digital cameras suffer from both low-spatial resolution and
      color-filtering, it is reasonable to address them in a unified context. In this
      paper, we propose a fast and robust hybrid method of super-resolution and
      demosaicing, based on a maximum a posteron estimation technique by minimizing a
      multiterm cost function. The L1 norm is used for measuring the difference between
      the projected estimate of the high-resolution image and each low-resolution
      image, removing outliers in the data and errors due to possibly inaccurate motion
      estimation. Bilateral regularization is used for spatially regularizing the
      luminance component, resulting in sharp edges and forcing interpolation along the
      edges and not across them. Simultaneously, Tikhonov regularization is used to
      smooth the chrominance components. Finally, an additional regularization term is
      used to force similar edge location and orientation in different color channels.
      We show that the minimization of the total cost function is relatively easy and
      fast. Experimental results on synthetic and real data sets confirm the
      effectiveness of our method.

PMID- 16435546
TI  - Self-similar random field models in discrete space.
AB  - Self-similar random fields are of interest in various areas of image processing
      since they fit certain types of natural patterns and textures. Current treatments
      of self-similarity in continuous two-dimensional (2-D) space use a definition
      that is a direct extension of the one-dimensional definition, which requires
      invariance of the statistics of a random process to time scaling. Current
      discrete-space 2-D approaches do not consider scaling, but, instead, are based on
      ad hoc formulations, such as digitizing continuous random fields. In this paper,
      we show that the current statistical self-similarity definition in continuous
      space is restrictive and provide an alternative, more general definition. We also
      provide a formalism for discrete-space statistical self-similarity that relies on
      a new scaling operator for discrete images. Within the new framework, it is
      possible to synthesize a wider class of discrete-space self-similar random fields
      and texture images.

PMID- 16435547
TI  - Context quantization by kernel Fisher discriminant.
AB  - Optimal context quantizers for minimum conditional entropy can be constructed by
      dynamic programming in the probability simplex space. The main difficulty,
      operationally, is the resulting complex quantizer mapping function in the context
      space, in which the conditional entropy coding is conducted. To overcome this
      difficulty, we propose new algorithms for designing context quantizers in the
      context space based on the multiclass Fisher discriminant and the kernel Fisher
      discriminant (KFD). In particular, the KFD can describe linearly nonseparable
      quantizer cells by projecting input context vectors onto a high-dimensional
      curve, in which these cells become better separable. The new algorithms
      outperform the previous linear Fisher discriminant method for context
      quantization. They approach the minimum empirical conditional entropy context
      quantizer designed in the probability simplex space, but with a practical
      implementation that employs a simple scalar quantizer mapping function rather
      than a large lookup table.

PMID- 16435548
TI  - Digital image processing techniques for the detection and removal of cracks in
      digitized paintings.
AB  - An integrated methodology for the detection and removal of cracks on digitized
      paintings is presented in this paper. The cracks are detected by thresholding the
      output of the morphological top-hat transform. Afterward, the thin dark brush
      strokes which have been misidentified as cracks are removed using either a median
      radial basis function neural network on hue and saturation data or a semi
      automatic procedure based on region growing. Finally, crack filling using order
      statistics filters or controlled anisotropic diffusion is performed. The
      methodology has been shown to perform very well on digitized paintings suffering
      from cracks.

PMID- 16435549
TI  - Regularization operators for natural images based on nonlinear perception models.
AB  - Image restoration requires some a priori knowledge of the solution. Some of the
      conventional regularization techniques are based on the estimation of the power
      spectrum density. Simple statistical models for spectral estimation just take
      into account second-order relations between the pixels of the image. However,
      natural images exhibit additional features, such as particular relationships
      between local Fourier or wavelet transform coefficients. Biological visual
      systems have evolved to capture these relations. We propose the use of this
      biological behavior to build regularization operators as an alternative to simple
      statistical models. The results suggest that if the penalty operator takes these
      additional features in natural images into account, it will be more robust and
      the choice of the regularization parameter is less critical.

PMID- 16435550
TI  - Stochastic methods for joint registration, restoration, and interpolation of
      multiple undersampled images.
AB  - Using a stochastic framework, we propose two algorithms for the problem of
      obtaining a single high-resolution image from multiple noisy, blurred, and
      undersampled images. The first is based on a Bayesian formulation that is
      implemented via the expectation maximization algorithm. The second is based on a
      maximum a posteriori formulation. In both of our formulations, the registration,
      noise, and image statistics are treated as unknown parameters. These unknown
      parameters and the high-resolution image are estimated jointly based on the
      available observations. We present an efficient implementation of these
      algorithms in the frequency domain that allows their application to large images.
      Simulations are presented that test and compare the proposed algorithms.

PMID- 16435551
TI  - 3-D shape estimation of DNA molecules from stereo cryo-electron micro-graphs
      using a projection-steerable snake.
AB  - We introduce a three-dimensional (3-D) parametric active contour algorithm for
      the shape estimation of DNA molecules from stereo cryo-electron micrographs. We
      estimate the shape by matching the projections of a 3-D global shape model with
      the micrographs; we choose the global model as a 3-D filament with a B-spline
      skeleton and a specified radial profile. The active contour algorithm iteratively
      updates the B-spline coefficients, which requires us to evaluate the projections
      and match them with the micrographs at every iteration. Since the evaluation of
      the projections of the global model is computationally expensive, we propose a
      fast algorithm based on locally approximating it by elongated blob-like
      templates. We introduce the concept of projection-steerability and derive a
      projection-steerable elongated template. Since the two-dimensional projections of
      such a blob at any 3-D orientation can be expressed as a linear combination of a
      few basis functions, matching the projections of such a 3-D template involves
      evaluating a weighted sum of inner products between the basis functions and the
      micrographs. The weights are simple functions of the 3-D orientation and the
      inner-products are evaluated efficiently by separable filtering. We choose an
      internal energy term that penalizes the average curvature magnitude. Since the
      exact length of the DNA molecule is known a priori, we introduce a constraint
      energy term that forces the curve to have this specified length. The sum of these
      energies along with the image energy derived from the matching process is
      minimized using the conjugate gradients algorithm. We validate the algorithm
      using real, as well as simulated, data and show that it performs well.

PMID- 16435552
TI  - Supervised range-constrained thresholding.
AB  - A novel thresholding approach to confine the intensity frequency range of the
      object based on supervision is introduced. It consists of three steps. First, the
      region of interest (ROI) is determined in the image. Then, from the histogram of
      the ROI, the frequency range in which the proportion of the background to the ROI
      varies is estimated through supervision. Finally, the threshold is determined by
      minimizing the classification error within the constrained variable background
      range. The performance of the approach has been validated against 54 brain MR
      images, including images with severe intensity inhomogeneity and/or noise, CT
      chest images, and the Cameraman image. Compared with nonsupervised thresholding
      methods, the proposed approach is substantially more robust and more reliable. It
      is also computationally efficient and can be applied to a wide class of computer
      vision problems, such as character recognition, fingerprint identification, and
      segmentation of a wide variety of medical images.

PMID- 16435553
TI  - Movie and video scale-time equalization application to flicker reduction.
AB  - Image flicker is a general film effect, which can be observed in videos as well
      as in old films, and consists of fast variations of the frame contrast and
      brightness. Reducing flicker of a sequence improves its visual quality and can be
      an essential first treatment before ulterior manipulations. This paper presents
      an axiomatic analysis of the problem, which leads to a global and fast method of
      "de-flicker," based on the scale-space theory. The stability of this process,
      called scale-time equalization, is ensured by the scale-time framework. Results
      on different sequences are given and show great visual improvement.

PMID- 16435554
TI  - Adaptive scale fixing for multiscale texture segmentation.
AB  - This paper addresses two challenging issues in unsupervised multiscale texture
      segmentation: determining adequate spatial and feature resolutions for different
      regions of the image, and utilizing information across different
      scales/resolutions. The center of a homogeneous texture is analyzed using coarse
      spatial resolution, and its border is detected using fine spatial resolution so
      as to locate the boundary accurately. The extraction of texture features is
      achieved via a multiresolution pyramid. The feature values are integrated across
      scales/resolutions adaptively. The number of textures is determined automatically
      using the variance ratio criterion. Experimental results on synthetic and real
      images demonstrate the improvement in performance of the proposed multiscale
      scheme over single scale approaches.

PMID- 16435555
TI  - [Anecdotes, blob, stories and persons. Is narrative research a priority for
      nurses?].

PMID- 16435556
TI  - [Working with elderly people].

PMID- 16435557
TI  - [The assessment of the nutritional status and risk profile of elderly residents].
AB  - An observational study in a long term geriatric care institution and medical
      wards, to systematically introduce the assessment of nutritional status,
      cognitive function and risk profile of residents, allowed the identification of
      "at risk" patients. METHODS: Data were collected on 198 residents, over a period
      of 6 months. RESULTS: The mean age was 86.6 years (range 80-99). Some data were
      not available for 54 patients (i.e. story of weight loss 3 months before
      admission: all of them had >90 years); 49% of patients were higly dependent and
      30% of patients were severely malnourished (malnutrition was prevalent in cancer
      patients). Of the 19 patients dead during the study 6 were malnuorished, 6 at
      risk and for 6 a thorough assessment was not possible. DISCUSSION: The prognostic
      importance weight loss over the last 6 months is widely aknowledged, however this
      information is not easily retrievable in geriatric populations; demented patients
      are more at risk of malnutrition. The collection of data on nutritional status
      allows the identification of patients who need a close surveillance and the
      implementation of preventive measures.

PMID- 16435558
TI  - [A very difficult question: a qualitative research from the nurses' perspective].
AB  - Aim of this paper is to identify what is a difficult question, according to
      nurses' perceptions. Since the knowledge on this area is limited, a qualitative
      method was preferred for a pilot study. METHODS: As part of a training exercise,
      fifty-one nurses were requested to recall, from their own experience, and to
      describe, a difficult question asked by a patient, that created problems to the
      nurse. Data were analysed with hermeneutical-interpretative methodology. RESULTS:
      Three main conceptual cores were identified: the characteristics of the difficult
      question; the "after the question"; and the source of the problem experienced.
      The first core is related to the content of the question but also to the
      characteristics of the person that formulates it, to the setting, and to the
      subjective perception of the time window. What happens after the question is
      related to the nurse's reactions. The third conceptual core is related to the
      interplay between different possible roles: patient, professional, and human
      being. The denominator of the three cores has to do with the emotional-relational
      dimension of the communication. This difficulty may partly be due to the lack of
      education in the management of the emotions.

PMID- 16435560
TI  - [Narratives, qualitative research and nursing research].

PMID- 16435559
TI  - [The antibiotic-lock therapy in oncoematology pediatric unit].
AB  - BACKGROUND: Central venous catheter (CVC) is the mandatory device for the
      administration of chemotherapy and support therapy to patients, particularly to
      children affected by malignancies. One of the major draw-backs of the extended
      use of CVC is the occurrence of CVC-related infections (CVC-RI) which represent
      an important cause of morbidity and mortality. In order to reduce the incidence
      of the removal of CVCs due to the persistent CVC -related infection, a new
      treatment based on a highly concentrated antibiotic lock solution instilled into
      the catheter lumen was proposed. AIMS: To describe the experience and results of
      the implementation of the lock therapy (associated to the use of connector CLC
      2000) in a sample of patients of the oncoematology paediatric ward of Padova
      Hospital. MATERIAL AND METHODS: Sample. 11 patients (4-21 years of age), affected
      by CVCRI. 10 patients had a 2 way tunneled catheter and one an implanted Port. A
      connector CLC 2000 was inserted to 9 patients with CVC. TREATMENT: An antibiotic
      lock therapy was administered for an average duration of 6.3 days: to the 9
      patients with CLC 2000 no heparin was added. Success was defined in terms of
      absence of feverfor at least 7 days in patients febrile at baseline;
      negativization of previously positive CVC blood culture without removal of CVC
      within 30 days starting from lock therapy. RESULTS: Only in one out of 11
      patients a negative outcome led to CVC removal. Problems with a malfunctioning
      device had to be solved also in one patient. CONCLUSION: The antibiotic lock
      therapy is a promising method to treat the CVCRI although the experience on
      oncohematological patients is limited. The use of connector CLC 2000 may improve
      the technique and reduce the problems.

PMID- 16435561
TI  - [Epidemiology starting from narrative based medicine].

PMID- 16435562
TI  - [ICU's psychosis: definition, treatment and nursing care].

PMID- 16435563
TI  - [The recruitment of nurses from foreign countries].

PMID- 16435564
TI  - [Children's health in the poorest European nation: the south of Italy].

PMID- 16435565
TI  - The use of violacein to study biochemical behaviour of Saccharomyces cerevisiae
      cells.
AB  - Violacein, a biochemical compound produced by Chromobacterium violaceum which has
      antichagasic properties, was used to study biochemical behaviour of Saccharomyces
      cerevisiae cells. At 20 microM and 40 microM, violacein did not alter the
      membrane potential (deltapsi) of S. cerevisae cells, which means that the
      integrity of the cell membrane was maintained. On the other hand, at 60 microM
      and 80 microM, violacein produced significant alterations in the membrane
      potential. This information will be very useful in using S. cerevisiae cells as a
      model to test the toxicity of new drugs before using in animals or human beings.

PMID- 16435566
TI  - The effects of gender and menopause on serum lidocaine levels in smokers.
AB  - It has been established that human cytochrome P450 (CYP) enzymatic activity is
      affected by gender, or by hormonal factors such as the menopause in women. Gender
      differences have a more pronounced effect on cytochrome (CYP) 3A4 isoenzyme
      activity, whereas cytochrome (CYP) 1A2 isoenzyme activity is mainly induced by
      chronic smoking. Lidocaine is frequently used in the treatment of hemodynamic
      changes following laryngoscopy and tracheal intubation during general anesthesia,
      and is metabolized by CYP3A4 and CYP1A2 isoenzymes in the liver. The aim of this
      study was investigate the effects of gender and menopause on serum lidocaine
      levels in smokers under general anesthesia. Six men, six premenopausal women and
      six postmenopausal women were enrolled in the study and received i.v. lidocaine
      (1 mg/kg) 1 minute before they underwent general anesthesia. Serum lidocaine
      concentrations were measured using the EMIT method at 1, 5, 10, 20, 40 and 60
      minutes post-administration. Statistical analyses were performed using the Mann
      Whitney U-test. No statistically significant differences were found regarding the
      area under curve (AUC(0-60) microg/mL/min), elimination half-life (t1/2 [min]) of
      lidocaine and in the measured levels of serum lidocaine at any time point between
      the study groups (p > 0.05). These results suggest that gender and menopause may
      have no significant effect on serum lidocaine levels in smokers.

PMID- 16435567
TI  - Adjuvant arthritis-induced changes on ampicillin binding in serum and tissues
      under the influence of non-steroidal anti-inflammatory drugs in rats.
AB  - Adjuvant arthritis, as a model for investigating rheumatoid arthritis (RA), is
      characterized by reduced plasma albumin levels and interferes with drug binding
      in the plasma and tissues (liver and bone). Ampicillin interacts with non
      steroidal anti-inflammatory drugs (NSAIDs) due to the acidic pk(a). The aim of
      this study was to investigate in vitro the concentrations of ampicillin in the
      serum, femur, mandible and liver proteins following the co-administration of
      ketoprofen, flurbiprofen, ibuprofen, oxyphenbutazone and ASA in adjuvant
      arthritis versus healthy control rats. Ampicillin binding was found to be reduced
      in the serum of arthritic rats, and ampicillin binding to serum proteins was also
      reduced under the influence of NSAIDs in the control animals. Differences in
      ampicillin binding were observed in the various tissues due to the effect of
      adjuvant arthritis as well as that due to the co-administration of NSAIDs. In
      conclusion, this in vitro study may provide a plausible explanation for the
      ampicillin-NSAIDs interaction and such a finding may be of therapeutic
      significance in the treatment of painful arthritic disease such as RA.

PMID- 16435568
TI  - Gender differences in limonin pharmacokinetics in rats.
AB  - In the present study, the pharmacokinetics of limonin (LM) were investigated in
      male and female rats. LM concentrations in the plasma were determined after the
      oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM
      3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were
      also analyzed following the oral administration of 36 mg/kg of the test product.
      It was found that the plasma concentrations of LM in female rats were
      significantly higher (P < 0.01) than those in male rats. Assessment of the
      effects of limonin based on the C(max) and AUC in female rats showed that levels
      were about 50-fold higher than those in male rats after oral administration of 36
      mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and
      AUC in female rats was found to be about 3-fold higher than those in male rats.
      The total excretion of LM in the urine and bile of female rats was also found to
      be significantly higher than in male rats, which displayed lower concentrations
      of LM in the tissues, amounting to around one-half to one-tenth of those in
      female rats, apart from levels in the rectum and duodenum. In conclusion, the
      present results demonstrate the existence of marked gender difference in LM
      pharmacokinetics in rats.

PMID- 16435569
TI  - Correlation between quinolone uptakes by BCECs in vitro and brain-to-plasma
      concentration ratios in rats.
AB  - Transport of 11 quinolones at the blood-brain barrier (BBB) was studied in vitro
      by using primarily cultured rat brain capillary endothelial cells (BCECs) and in
      vivo brain-to-plasma concentration ratios. In vitro, when cells reached
      confluence, a time course of quinolone uptake was recorded by incubation with a
      medium contraining quinolones 20 microg/ml at 37 degrees C. A simple two
      compartment model was used for fitting the uptake time course and corresponding
      uptake parameters were estimated. In vivo rats were anesthetized, after in 10
      mg/kg of quinoloes followed by infusion of 4 mg/kg/h for 2 hours, the drug
      concentrations in plasma and brain were measure and brain-to-plasma concentration
      ratios were calculated. Result showed that sparfloxacin and prulifloxacin have
      higher uptakes by BCECs and brain-to-plasma concentration ratios, compared with
      other quinolones, which indicated that the two drugs more easily penetrate into
      BBB. A good correlation between uptakes by BCECs and brain-to-plasma
      concentration ratios was found. These results demonstrated uptakes by BCECs in
      vitro might give prediction of brain-to-plasma ratio for quinolones.

PMID- 16435570
TI  - In vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino
      3-methyl-4(3H)-quinazolinone in rats.
AB  - The aim of this study was to investigate by HPLC the in vivo metabolism of 2-[1'
      phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone
      as a substrate, and as a model compound in rats. The substrate was dissolved in
      DMSO/water (1:4) and administered intraperitoneally at a dose of 100 mg/kg in a
      volume of approximately 0.1 mL. Blood samples were taken before and 30 min, 1.5,
      3, 6, 9, 11, 30 and 48 h after i.p. drug administration. The chromatographic
      separation of the substrate and its metabolites was performed using a stainless
      steel Novopak C18 column (150 x 4.6 mm i.d., 5-microm particle size). The optimal
      composition of the mobile phase was reached by introducing different mixtures of
      pure acetonitrile and water in a linear gradient system. Following the
      biotransformation of this compound, 2-hydrazino-3-methyl-4(3H)-quinazolinone (M1)
      and 3-(3-chlorophenyl)-1-phenylprop-2-en-1-one (M2) derivatives were identified
      together with substrate by comparing them to reference standards using HPLC
      UV/DAD. In addition, the composition of these metabolites and substrate was
      confirmed by LC-MS in plasma.

PMID- 16435571
TI  - Absorption profiles of sanchinoside R1 and ginsenoside Rg1 in the rat intestine.
AB  - Panax notoginseng is used as a therapeutic agent in Chinese medicine for stopping
      hemorrhage and also as a general health remedy. Although Panax notoginseng
      saponins (PNS) are currently attracting attention due to their hemorheological
      properties, the absorption profiles of PNS have still not been fully
      investigated. In the present study, an in situ intestinal perfusion rat model was
      used to investigate the absorption mechanism of sanchinoside R1 (R1) and
      ginsenoside Rg1 (Rg1), two main components of PNS. Quantitative analysis methods
      for R1 and Rg1 were first established, then concentrations of R1 and Rg1 in the
      perfusate were measured in real time through assessment of circulating perfusate
      in the rat small intestine. The absorption rate constant (k(a)) values for R1
      were 0.1223, 0.0946 and 0.0904 h(-1) at a dose of 1, 10 and 100 mg respectively,
      while those of Rg1 were 0.1169, 0.1134 and 0.1089 h(-1) at a dose of 1, 10 and
      100 mg respectively. The optimal absorption site for both of these compounds was
      found to be the duodenum, which indicated that the bioavailability of the orally
      administered PNS preparation was relatively low. Finally, the effect of certain
      absorption promoters on the absorption rates of R1 and Rg1 was investigated. It
      was found that carbomer and borneol could enhance the permeability of R1 and Rg1
      on the intestinal wall (P < 0.05), which indicated that a suitable absorption
      promoter could improve the absorption of PNS and increase its bioavailability.

PMID- 16435572
TI  - Pharmacokinetics of Astragaloside IV in rats by liquid chromatography coupled
      with tandem mass spectrometry.
AB  - Pharmacokinetics of Astragaloside IV (AGS-IV) in rats was studied by high
      performance liquid chromatography coupled with tandem mass spectrometry. The
      concentration in plasma was determined after i.v. administration of 1, 2, 4 mg/kg
      and p.o. administration of 20 mg/kg of AGS-IV. The AUC were linearly correlated
      to doses. Recoveries of AGS-IV in bile, urine and feces were also analyzed
      following i.v. dose of 2 mg/kg. Cumulative recovery of AGS-IV in bile reached
      30.8% in 24h. Cumulative recovery of AGS-IV in urine and feces was 52.14%, which
      indicates that about 50% of AGS-IV was metabolized in vivo. The bioavailability
      of AGS-IV after p.o. administration was found to be 3.66%. These findings provide
      useful information for the research and development of AGS-IV and other potential
      agents.

PMID- 16435573
TI  - Identification of enzymes involved in phase I metabolism of ciclesonide by human
      liver microsomes.
AB  - Ciclesonide, a novel inhaled corticosteroid, is currently being developed for the
      treatment of asthma. Here, the enzymes catalysing the human hepatic metabolism of
      ciclesonide were investigated. When incubated with human liver microsomes (HLM),
      [14C]ciclesonide was first metabolised to the active metabolite M1 (des
      isobutyryl-ciclesonide, des-CIC) and to at least two additional metabolites, M2
      and M3. M3 comprises a 'family' of structurally similar metabolites that are
      inactive. 16-Hydroxyprednisolone was also formed in microsomal incubations of
      [14C]des-CIC, but at approximately one-tenth the amount of both M2 and M3. bis-p
      Nitrophenylphosphate and SKF 525-A respectively inhibited des-CIC formation from
      [14C]ciclesonide by 82% and 49% and M2/M3 formation by 82-84% and 87-89%.
      Regression analysis showed significant negative correlations (r = -0.96, -0.79
      and -0.71, respectively) of M2 formation with CYP3A4/5, CYP2B6 and CYP2C8
      activities; M3 formation significantly correlated with CYP4A9/11 (r = 0.47).
      Troleandomycin and diethyldithiocarbamate inhibited M2 and M3 formation by 85%
      and 45%, respectively. Sulphaphenazole and quinidine had no inhibitory effects.
      CYP3A4 Supersomes catalysed notable formation of both M2 and M3 from [14C]des
      CIC; CYP2C8 and CYP2D6, but not CYP4A11 formed smaller amounts. It is concluded
      that the human hepatic metabolism of ciclesonide is primarily catalysed by one or
      more esterases and, subsequently, by CYP3A4.

PMID- 16435574
TI  - Effects of whole-body gamma irradiation and 5-androstenediol administration on
      serum G-CSF.
AB  - 5-Androstenediol (5-AED) is a natural circulating adrenocortical steroid hormone
      that interconverts in vivo with other members of the 5-androstene family of
      steroids: dehydroepiandrosterone and 5-androstenetriol. These steroids stimulate
      immune responses and resistance to infection. 5-AED has been identified as a
      systemic radiation countermeasure that enhances survival in mice exposed to gamma
      irradiation and ameliorates radiation-induced neutropenia in mice and nonhuman
      primates. 5-AED mitigates radiation-induced decreases in platelets, natural
      killer (NK) cells, red blood cells, and monocytes. Administration of 5-AED causes
      functional activation of circulating granulocytes (phagocytic ability), monocytes
      (oxidative burst), and NK cells (surface CD11b expression). The effects of 5-AED
      on survival and hematological parameters are consistent with induction of
      hematopoietic cytokines. To test this hypothesis, we measured serum cytokines by
      ELISA, Luminex, and a cytokine array. A cytokine array was used for 62 different
      cytokines, chemokines, growth factors, and soluble receptors. 5-AED caused
      significant increases in circulating granulocyte colony-stimulating factor (G
      CSF) in irradiated and unirradiated animals as observed with ELISA and Luminex.
      The cytokine array results suggest induction of G-CSF and additional cytokines,
      and related molecules. Since G-CSF is an important hematopoietic cytokine, the
      results support our hypothesis that the previously observed increases in numbers
      of hematopoietic progenitors, circulating innate immune cells and platelets, and
      functional activation of granulocytes, monocytes, and NK cells result from a
      cytokine cascade induced by 5-AED.

PMID- 16435575
TI  - Successful treatment with cyclosporine A of HCV-driven chronic liver disease
      mimicking autoimmune hepatitis in a patient with common variable
      immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is the commonest primary immunodeficiency
      disease characterized by defective antibody production and various degrees of T
      cell numbers abnormality or impaired proliferation to mitogens. Clinical features
      include recurrent bacterial sinopulmonary and gastrointestinal infections.
      Autoimmunity is very common in CVID, occurring in approximately 25% of the
      patients particularly with autoimmune thrombocytopenia, hemolytic anemia,
      inflammatory bowel disease, and rheumatoid arthritis. Persistent antigen
      stimulation, secondary to a defective eradication of pathogens followed by a
      compensatory exaggerated chronic inflammatory response, is the primary cause
      leading to autoimmunity. Here we describe a girl with CVID in whom a chronic
      liver disease mimicking autoimmune hepatitis developed after hepatitis C virus
      infection. The immunosuppressive treatment with cyclosporine A proved effective
      in reversing liver disease.

PMID- 16435576
TI  - T cell tolerance induced by histone deacetylase inhibitor is mediated by P21cip1.
AB  - MEB [n-butyrate 2-(4-morpholinyl) ethyl butyrate hydrochloride], a histone
      deacetylase inhibitor and G1 blocker, has been shown to induce unresponsiveness
      in antigen-activated Th1 cells. MEB was tested for here for its ability to
      inactivate naive alloantigen-specific T cells from DBA/2 and C57BL/10 mice. Since
      T cells from these two strains of mice have been shown to differ in their cell
      cycle regulation, it we hoped that this comparison would provide information
      concerning the role of cycle regulatory proteins in mediating MEB-induced T cell
      unresponsiveness. MEB inhibited proliferation in a one-way mixed lymphocyte
      reaction (MLR) in which spleen cells from DBA/2 mice (H-2d) or C57BL/10 mice (H
      2b) were stimulated with spleen cells from C57BL/10 or DBA/2 mice, respectively.
      C57BL/10 responder T cells isolated from the MEB-treated primary MLR remained
      unresponsive to alloantigen following restimulation in a secondary MLR that did
      not contain MEB. T cells from DBA/2 mice were less sensitive to MEB-induced
      unresponsiveness and required a longer exposure or pretreatment with IL-2 to
      become tolerant. In all cases responsiveness to MEB-induced tolerance in the
      alloantigen-stimulated T cells corresponded with the levels of the cyclin
      dependent kinase inhibitor p21cip1. Additional experiments showed that T cells
      from p21cip1-deficient mice, unlike T cells from p21cip1 wild-type littermates,
      were resistant to MEB-induced tolerance. These results underscore the role of
      p21cip1 in mediating T cell tolerance induced by the histone deacetylase
      inhibitor MEB.

PMID- 16435577
TI  - Attempted passive prophylaxis with a monoclonal anti-Burkholderia pseudomallei
      exopolysaccharide antibody in a murine model of melioidosis.
AB  - Melioidosis is a severe gram-negative infection caused by the facultative
      intracellular bacterium Burkholderia pseudomallei, which is responsible for a
      broad spectrum of symptoms in both humans and animals. No licensed vaccine
      currently exists. This study evaluated the protective effect of a monoclonal
      antibody (Mab Ps6F6) specific to B. pseudomallei exopolysaccharide in an outbred
      murine model of sub-acute melioidosis. When administered before the infectious
      challenge, Ps6F6 significantly increased resistance to infection and restrained
      bacterial burden in the spleen over a 30-days period. Patterns of IFN-gamma
      production were similar in the treated and non treated groups of mice. However,
      Ps6F6 lowered IFN-gamma levels over the duration of the assay period, except on
      day 1, suggesting a transient and rapid production of IFN-gamma under Ps6F6
      control. Minor but persisting increases occurred in IL-12 levels while TNF-alpha
      was detected only in the controls at the later stages of infection. No IL-10
      secretion was detected in both groups of mice. These data suggest that passive
      prophylaxis with Mab Ps6F6 provide a moderate and transient induction of
      inflammatory responses in infected mice but failed to trigger a sterilizing
      protective immunity.

PMID- 16435578
TI  - Restoration of thymic homeostasis in a tumor-bearing host by in vivo
      administration of medicinal herb Tinospora cordifolia.
AB  - In vivo administration of alcoholic extract of medicinal plant Tinospora
      cordifolia (TC) to mice bearing a spontaneous T cell lymphoma designated as
      Dalton's lymphoma prevented tumor growth-dependent regression of thymus. TC was
      found to augment proliferation of thymocytes with a concomitant decrease in
      thymocyte apoptosis. It also resulted in a decrease in the number of Hassal's
      corpuscles. Restoration of thymus homeostasis was caused by TC-dependent
      augmentation in production of thymocyte growth promoting cytokines Interleukin-2
      and Interferon-gamma from thymocytes. TC was found to downregulate thymocyte
      apoptosis by modulation of Caspase pathway. TC administration retarded tumor
      growth and prolonged survival of tumor-bearing mice. The possible mechanisms are
      discussed.

PMID- 16435579
TI  - Effects of PCBs 52 and 77 on Th1/Th2 balance in mouse thymocyte cell cultures.
AB  - Polychlorinated biphenyls (PCBs) are industrial chemicals that have been released
      into the environment, resulting in widespread and persistent contamination. PCBs
      exist as 209 different congeners depending on the chlorine substitution on the
      biphenyl rings, and the physical properties and toxic effects of different PCB
      congeners are structure-dependent. We have tested an ortho-substituted,
      noncoplanar congener, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), and a non-ortho
      substituted coplanar congener, 3,3',4,4'-tetrachlorobiphenyl (PCB 77), for their
      effects on the T helper 1 (Th1) and T helper 2 (Th2) lymphocyte balance. The
      experiments were performed in 10 microg/ml concanavalin A (Con A)-stimulated and
      nonstimulated thymocytes for determination of cytokine production profiles.
      Interferon-gamma (produced by Th1 cells) and interleukin (IL)-10 (produced by Th2
      cells) concentrations were measured in the supernatants at 12 and 24 hr after
      treatment with PCBs. PCBs 52 and 77 caused significant increases in interferon
      gamma levels at 12 and 24 hr in both Con A-stimulated and nonstimulated media. IL
      10 levels were significantly reduced at two interval periods by PCBs 52 and 77 in
      cultures with and without Con A. Our results show that the cytokine production
      profile was significantly shifted to Th1 by both ortho-substituted and coplanar
      PCB congeners in mouse thymocyte cultures.

PMID- 16435580
TI  - Artemether: a new therapeutic strategy in experimental rheumatoid arthritis.
AB  - The current research was designed to determine the effect of artemether in
      treatment of experimental rheumatoid arthritis. Collagen-induced arthritis was
      induced in Lewis rats. The intramusculary administration of artemether (ART) and
      intraperitoneally injection of methotrexate (MTX) were started on day 25
      postimmunization and continued until final assessment on day 35. During this
      period, clinical examination was taken intermittently. The anticollagen type II
      antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness
      were then removed for histopathology and radiography assay. The biocompatibility
      of ART and MTX were assessed using fibrosarcoma cell line. Data showed that i.m.
      injection of ART to arthritic rats induced a significant reduction in paw edema.
      This beneficial effect was associated with a significant decrease in anti-CII
      antibody response compared with untreated rats. Histopathological assessment
      showed a reduced inflammatory cell infiltrate in joints of treated rats; tissue
      edema, and bone erosion in the paws were markedly reduced following ART therapy.
      Furthermore, our radiography results paralleled our histological findings.
      Cytotoxicity analysis of ART showed greater tolerability compared with MTX.
      Treatment with ART significantly diminished NO formation in treated rats compared
      with nontreated controls. Our data shed light on the therapeutic efficacy of
      artemether in experimental rheumatoid arthritis compared with a choice drug
      (methotrexate), and it may be offered as a second-line drug in treatment of
      rheumatoid arthritis.

PMID- 16435581
TI  - p38 MAPK and NF-kappaB on IL-6 release in human gingival fibroblasts.
AB  - The induction of interleukin-6 (IL-6) using a proinflammatory cytokine (IL-1beta)
      was studied in human gingival fibroblasts (HGFs) in relation to p38 MAPK and NF
      kappaB transcription factor. When added to HGFs, IL-1beta had a stimulatory
      effect on the production of IL-6, and this effect was significantly reduced by
      SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6
      release also was reduced by the addition of pyrrolidine dithiocarbamate or NF
      kappaB SN50, which has been reported as potent NF-kappaB inhibitor. Both the NF
      kappaB inhibitors in the presence of SB203580 had more inhibitory effect on IL-6
      release. IL-13 stimulated NF-kappaB binding affinity as well as p38 MAP kinase
      activation, leading to the release of IL-6. However, a specific inhibitor of p38
      MAPK, SB203580, had no effect on the NF-kappaB activation, and both the NF-kappaB
      inhibitors failed to reduce the p38 MAPK activation in the IL-1beta-stimulated
      HGFs. These results strongly suggest that both p38 MAPK and NF-kappaB are
      required in IL-1beta-induced IL-6 synthesis and that these two IL-1beta-activated
      pathways can be primarily dissociated.

PMID- 16435582
TI  - Ultrafiltered pig leukocyte extract (UPLE, IMUNOR) potentiates hematopoiesis
      stimulating effects of G-CSF in vitro and improves the outcome of treatment of
      hematopoietic radiation damage in mice with G-CSF.
AB  - Ultrafiltered pig leukocyte extract (UPLE, Imunor), a heterogeneous mixture of
      low molecular weight (<10 kD) substances released from disintegrated pig
      leukocytes was tested from the point of view of its hematopoiesis-modulating
      activities using experiments in vitro and in vivo. Attention was focused
      especially on evaluation of the contingent ability of UPLE to potentiate the
      hematopoiesis-stimulating effects of recobinant human granulocyte colony
      stimulating factor (G-CSF). Experiments in vitro revealed the capability of sera
      from mice administered UPLE perorally (p.o.) to stimulate proliferation of
      progenitor cells for granulocytes and macrophages (GM-CFC) in cultures of normal
      bone marrow cells. In addition, UPLE, as well as sera from mice given UPLE, added
      to the cultures in combination with G-CSF enhanced the numbers of GM-CFC
      significantly over those induced by sera after administration of either of the
      preparations alone. In in vivo experiments, UPLE was found to increase the counts
      of GM-CFC per femur and femoral bone marrow cellularity in sublethally irradiated
      mice when administered p.o. after irradiation in combination with G-CSF in
      comparison with the effects of G-CSF alone. These results indicate the
      possibility of using UPLE, a commercially available preparation, for treatment of
      hematopoietic suppression of various etiology.

PMID- 16435584
TI  - Bee venom, immunostimulant or immunosuppressor? Insight into the effect on matrix
      metalloproteinases and interferons.
AB  - The current evidence has defined conflicting properties for bee venom. The goal
      of this study was to determine whether bee venom (BV) is an immunosuppressor or
      immunostimulant. The WEHI-164, HT-1080, and K562 cell lines were used for
      assaying toxicity, proliferative response, matrix metalloproteinase-2 and -9 (MMP
      2 and MMP-9) activity, and interferon production. The Australian and Iranian BV
      (ABV and IBV) were used at concentrations of 0.025-1 microg/ml in triplicate and
      2-fold dilutions. MMP-2 and -9 activities were evaluated using the zymography
      method. The production of interferons (IFN-alpha and IFN-beta) were assessed
      using enzyme-linked immunoassay procedure. Our results show no significant
      difference between two sources of honeybee venom (ABV and IBV) when they are
      added to an identified cell line, whereas the response of various cell lines
      against BV could be different. The increasing amounts of ABV and/or IBV (between
      doses 0.025-0.5 microg/ml) to human monocyte cell line (K562) exhibit a
      significant increase in proliferative response. Our data show that the
      immunomodulatory effect of ABV and/or IBV on MMP-2 and MMP-9 activity in both
      cell culture media, WEHI-164 and K562, is similar. The stimulatory effect of BV
      on MMP-2 and -9 activities is occurred between doses 0-0.05 microg/ ml. In
      contrast, the inhibitory effect of BV on these two MMPs is seen at concentrations
      of >0.05 microg/ml. The ABV and/or IBV has no influence on IFN-alpha production
      in cell culture media, whereas adding the BV to K562 cell line could
      significantly increase the production level of IFN-beta only on day 8
      posttreatment. We conclude that time- and dose-dependent response as well as the
      type of treated cell line could determine the immunosuppressive and/or
      immunostimulant property of bee venom that could be effective in future
      therapeutic strategies.

PMID- 16435583
TI  - Anti-inflammatory effect of lemon mucilage: in vivo and in vitro studies.
AB  - The mucilage extracted from a lemon juice centrifugation pulp was studied for its
      anti-inflammatory effect in rat. In vivo the lemon mucilage significantly
      inhibited carrageenan-induced edema in rat paw from 59% to 73.5% showing the
      highest effect at the third hour. In vitro, at the doses of 10(-8), 10(-6), 10(
      4) or 10(-2) mg/mL the lemon mucilage stimulated the superoxide anion production
      in rat testing neutrophils in whole blood but inhibited it in FMLP stimulated
      cells at the dose of 10(-2) mg/mL. The neutrophils of rats receiving p.o. the
      lemon mucilage for 21 days showed a significant decrease of 45.5% in O2-
      generation after FMLP stimulation, and a not-significant increase after phorbol
      12-myristate-13-acetate (PMA) or zymosan stimulation. Since the activity on
      zymosan- and PMA-induced O2- production was not significant, the inhibition
      exerted by FMLP in rat neutrophils occurred mainly through the blockade of
      phospholipase D.

PMID- 16435585
TI  - Effect of Danchunwhangagam on LPS or DFX-induced cytokine production in
      peripheral mononuclear cells of cerebral infarction patients.
AB  - The Danchunwhangagam (DCWGG) has long been used for various cerebrovascular
      diseases. However, little scientific investigation has been carried out.
      Cytokines involved in the regulation of inflammatory reactions and immune
      responses may play a role in the pathogenesis of cerebral infarction (CI). The
      aim of the present study is to investigate the effect of DCWGG on the production
      of proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from
      CI patients. The amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1alpha, IL-1beta, IL-6, and IL-8 in PBMC culture supernatant was significantly
      increased in the lipopolysaccaride (LPS)- or desferrioxamine (DFX)-treated cells
      compared with unstimulated cells. We showed that DCWGG inhibited the production
      of TNF-alpha, IL-1alpha, IL-1beta IL-6, and IL-8 induced by LPS in a dose
      dependent manner. Also, DCWGG inhibited TNF-alpha, IL-1alpha, IL-beta, IL-6, and
      IL-8 production-induced DFX in dose-dependent manner. These results suggest that
      DCWGG might have regulatory effects on LPS- or DFX-induced cytokine production,
      which might explain its beneficial effect in the treatment of CI.

PMID- 16435586
TI  - Outcomes and outcome measures: measuring what matters is in the eye of the
      beholder.

PMID- 16435587
TI  - Best practice in occupational therapy: program characteristics that influence
      vocational outcomes for people with serious mental illnesses.
AB  - BACKGROUND: Despite the known benefits of work for people with mental illnesses,
      vocational outcomes of this group remain poor. Attempts at comparing the efficacy
      of various models of service delivery have met with limited success due to
      variations across studies. PURPOSE: The purpose of this paper is to provide
      information about key characteristics related to outcomes in the field of
      vocational rehabilitation for people with serious mental illnesses. METHOD: A
      comprehensive review of literature published between 1990 and 2003 was conducted,
      resulting in 39 articles for analysis. RESULTS: A set of twelve characteristics
      was identified that appear to influence vocational outcomes across models. These
      characteristics relate to the types of services offered, the manner in which
      services are delivered, and the work environment. PRACTICE IMPLICATIONS: The
      authors suggest these characteristics can be incorporated across models and
      practice settings. The findings are discussed in terms of implications for best
      practice in occupational therapy.

PMID- 16435588
TI  - The process of change: listening to transformation in meaning perspectives of
      adults in arthritis health education groups.
AB  - PURPOSE: This study explored client experiences in two different arthritis
      education groups to develop an understanding of meaningful group experiences in
      the process of change leading to desired health outcomes. METHOD: A qualitative
      framework with an inductive, descriptive, phenomenological method guided the
      study. Ten participants with rheumatoid or inflammatory arthritis were recruited.
      Individual and focus group interviews provided descriptions of experiences.
      RESULTS: Arthritis education group experiences led to improved client perceptions
      of ability to cope with chronic disease through a process of change in feelings,
      values and beliefs known as meaning perspectives. The change in meaning
      perspectives occurred through perceptions about disease, self and illness.
      PRACTICE IMPLICATIONS: This study provides important insights into the client's
      process of change in meaning perspectives that can lead to health behaviors and
      desired health outcomes. The study demonstrates the use of the group context as a
      tool to enable the process of change.

PMID- 16435589
TI  - Home and community occupational therapy for children and youth: a before and
      after study.
AB  - BACKGROUND: There has been an increased focus on home care service provision in
      recent years, yet there are few data available about the provision of home and
      community occupational therapy for children and youth. PURPOSE: To evaluate key
      elements of a service provision model for home care occupational therapy in terms
      of occupational performance outcomes, perception of care and cost. METHODS:
      Eleven centres in Ontario and Quebec recruited 167 children and youth up to 18
      years of age to a before and after study of occupational therapy services in the
      home and community. Occupational performance, quality of life and costs were
      measured at baseline and study end. Perception of care was measured at study
      completion. RESULTS: A statistically and clinically significant improvement in
      occupational performance was demonstrated (p < 0.001). The clients' families gave
      high ratings to the process of care provided by the occupational therapists.
      These data did not demonstrate a clear relationship between amount of service,
      cost and occupational performance outcome. PRACTICE IMPLICATIONS: Children
      receiving home and community occupational therapy services change in their
      occupational performance abilities. These changes are not directly related to the
      amount or focus of the occupational therapy services.

PMID- 16435590
TI  - Targeted applications of the Canadian Occupational Performance Measure.
AB  - BACKGROUND: The Canadian Occupational Performance Measure (COPM) is an outcome
      measure designed to assess performance and satisfaction with occupation. It was
      developed to coincide with the occupation-focused, client-centred Canadian Model
      of Occupational Performance. PURPOSE: The COPM has been a feature of the
      occupational therapy landscape for approximately 15 years and has pervaded the
      consciousness of occupational therapists around the world. In this paper, we
      examine issues associated with application of the COPM in targeted clinical and
      non-clinical situations. RESULTS: The paper suggests considerations required to
      ensure that the highest quality of information is derived from the COPM in all
      situations. PRACTICE IMPLICATIONS: Although the paper emphasizes the centrality
      of the client-centred approach, it also demonstrates the flexibility and
      adaptability of the COPM to different situations, clients, settings and purposes.

PMID- 16435591
TI  - Measuring the outcomes of word cueing technology.
AB  - BACKGROUND: Measurement of assistive technology outcomes is complex because many
      factors (e.g., environment and model of service delivery) influence the
      successful use of the technology. PURPOSE: Using the example of measuring the
      outcomes of word cueing technology, this paper presents an approach for measuring
      assistive technology outcomes. METHOD: The Canadian Occupational Performance
      Measure (COPM) was administered to 29 children with physical and learning
      disabilities, between the ages of 3.9 and 19 years. Participants were provided
      with WordQ, a software program designed to assist the development of writing
      skills. Follow-up data were collected through telephone interviews. RESULTS: The
      COPM findings supported the effectiveness of WordQ Version 1 to enhance written
      productivity, with a mean performance change score of 3.5 (SD = 1.5). The COPM
      was an effective tool for measuring clients' perceived outcome of word cueing
      technology. Telephone interview was considered a successful method for collecting
      outcome data. PRACTICE IMPLICATIONS: A mix of tools and methodologies should be
      used to gain a comprehensive understanding of the impact of assistive technology.

PMID- 16435592
TI  - Clinical report: use of the Canadian Occupational Performance Measure in vision
      technology.
AB  - BACKGROUND: The Canadian Occupational Performance Measure (COPM) has gained wide
      acceptance in general occupational therapy research and practice, however, the
      use of the COPM in assistive technology assessments and outcomes is not as well
      documented. PURPOSE: This clinical report discusses the utility of the COPM in
      assistive technology, as illustrated by the assessment and follow-up of clients
      requiring high technology vision aids. RESULTS: The COPM makes important
      contributions to the outcomes of providing vision aids. The COPM ensures a needs
      review that incorporates all areas of occupational performance, which in turn
      directs the clinician to match the technology to client needs. From a clinical
      perspective, the quantitative follow-up data are helpful to determine clients'
      improvement in occupational performance as well as their satisfaction with the
      assistive technology. For administrative purposes, the COPM results provides
      accountability to the funding agency. PRACTICE IMPLICATIONS: The COPM can be
      readily integrated into the assessment and follow-up of assistive technology
      service delivery and adds value to both components of the process.

PMID- 16435593
TI  - Selected bibliography on outcomes in occupational therapy.

PMID- 16435594
TI  - [Management of occlusive peripheral arterial disease of the lower limbs].

PMID- 16435596
TI  - [Acute or sub-acute thrombosis of steel stents].
AB  - The use of coronary endoprostheses has greatly contributed to the improvement in
      the results of coronary angioplasty. Nevertheless, the risk of stent thrombosis
      remains a major preoccupation. We studied a retrospective series of 2997 patients
      who had undergone coronary angioplasty between 1999 and 2003. 36 patients (1.2%)
      had an acute or sub-acute stent thrombosis, occurring in two thirds of cases in
      the first 4 days with particularly serious clinical consequences: 5 deaths
      (13.8%) and 27 myocardial infarctions (75%). A comparison between the 2 groups of
      patients with thrombosis (n = 36) and without thrombosis (n = 2961) using
      multivariate analysis determined predictive factors for thrombosis: systolic LV
      dysfunction < 40% (p < 0.0001 OR 3.8 [2-7.3]), angioplasty for lesions on the
      anterior interventricular artery (p < 0.0001 OR 2.7 [1.4-5]), angioplasty
      performed in the acute phase of MI (p < 0.05 OR 13.9 [6.7-29.2]), B2-type complex
      lesions (p < 0.01 OR 2.5 [1.3-5]), residual dissection at the dilated site (p <
      0.02 OR 5.1 [1.4-18.2]). More than ever, acute thrombosis remains a topical
      subject. This study emphasises the incidence of steel stent thrombosis; the
      clinical consequences and the predictive factors for early occlusion.

PMID- 16435595
TI  - [Risk factors management in 5708 ambulatory patients suffering from peripheral
      vascular disease followed in urban practices].
AB  - STUDY OBJECTIVE: we examined the management of risk factors in patients suffering
      from obliterating peripheral arterial disease (OPAD), in urban medical practice.
      METHODS: PRISMA, ECLAT1 and APRES are surveys based on urban medicine in France.
      These 3 studies have allowed a compilation of data pertaining to the control of
      risk factors in patients suffering from one or more clinical manifestations of
      atherothrombosis, including cerebral vascular accident, coronary insufficiency or
      OPAD. The study population was divided among patients with isolated OPAD, versus
      OPAD associated with coronary artery disease (CAD), versus OPAD associated with
      cerebral vascular disease. RESULTS: a total of 5 708 patients with stable OPAD
      were included among the 3 studies. Risk factors were not managed in the majority
      of patients, including 62.6% of hypercholesterolemic patients, 71.1% of
      diabetics, and 77.4% of hypertensive patients. Overall, the control of risk
      factors was less satisfactory in patients with OPAD than in patients with CAD.
      Smoking (70.6% current or past smokers) remains a major risk factor in OPAD. The
      proportion of current smokers was significantly higher is the group with isolated
      OPAD than in the other 2 groups of patients (p < 0.0001). CONCLUSIONS: The
      control of risk factors in patients with OPAD is suboptimal, mainly because of
      failure to reach the therapeutic goals, rather than because of poor medical
      management. It is important that recent recommendations be implemented in medical
      practice. Awareness of the primary physicians will be key in the optimisation of
      treatment prescriptions and, above all, in the achievement of a higher level of
      clinical performance.

PMID- 16435597
TI  - [Early non-obstructive thrombosis of mechanical mitral valve prostheses].
AB  - Transoesophageal echocardiography has shown a high incidence on non-obstructive
      thrombosis after mitral valve replacement with a mechanical prosthesis. The
      unpredictable outcome and the period during which the complication arises make
      treatment difficult. The aim of this study was to assess the tolerance and
      efficacy of the association of long-term heparin and oral anticoagulation, as
      recommended in this indication. All patients undergoing mitral valve replacement
      with a mechanical prosthesis between June 1999 and July 2001 were systematically
      included and studied by transoesophageal echocardiography in the immediate
      postoperative period. Those with non-obstructive thrombosis at least 5 mm in size
      were treated by heparin and oral coagulation until the thrombus disappeared on
      transoesophageal echocardiography. One hundred and fourteen patients undergoing
      120 mitral valve replacements (6 reoperations) underwent transoesophageal
      echocardiography and non-obstructive thrombi measuring at least 5 mm were found
      on 26 occasions (21.7%). The association of heparin and oral coagulation was
      maintained for 7 to 115 days (average 20 days). No thromboembolic or haemorrhagic
      complications and no deaths were observed during this period. Two patients were
      treated with danaparoid and oral anticoagulation because of heparin-induced
      thrombocytopenia before the diagnosis. None of the patients died during follow-up
      (average 49 months); there were 4 recurrent non-obstructive thromboses, three of
      which were complicated by thromboembolic events with no sequellae in the first 8
      months, again treated effectively with the association of heparin and oral
      anticoagulants; two cerebral embolic events without sequellae were observed
      without a demonstrable non-obstructive thrombus on transoesophageal
      echocardiography. The authors conclude that the association of heparin and oral
      anticoagulants seems well tolerated and effective in this small population and
      this would justify a large scale clinical trial.

PMID- 16435598
TI  - [Role of visual analysis of first-pass contrast-enhanced MRI in reperfused
      myocardial infarction].
AB  - The aim of this work is to evaluate the relationship between improvement of
      regional myocardial function and visual analysis of contrast-enhanced (CE) MRI in
      patients after acute myocardial infarction. MRI was performed on 19 patients 1
      and 11 weeks after a reperfused acute myocardial infarction. Perfusion data
      (first-pass images [FPI] and delayed CE images) were acquired after an
      intravenous bolus of gadolinium-DTPA and visually analyzed using a 17 segment
      model. Each segment was then classified in 3 groups, according to the presence or
      absence of FPI and CE patterns at baseline study: group 0: normal-appearing
      segments; group 1: segments with delayed hyper-enhancement but no early hypo
      enhancement; group 2: segments with early hypoenhancement. Relative Wall
      thickening (RWT) was analyzed in each segment and its improvement evaluated in
      each group. Between first MRI and follow-up study, a significant improvement of
      RWT occurred in group 1 (mean +/- SD) [from 43.43 +/- 26.59% to 76.71 +/- 47.38%;
      p = 0.001] but not in group 2 (from 32.73 +/- 25.58% to 39.57 +/- 30.57%; p =
      NS). In group 0, RWT despite normal value at baseline study exhibited a
      significant improvement at follow-up (from 65.23 +/- 46.52% to 79.73 +/- 48.46%;
      p = 0.0015). In conclusion, the combined analysis of early and delayed perfusion
      abnormalities in MRI in the week following myocardial infarction can predict
      myocardial viability and allows in the future an evaluation of the efficacy of
      perfusion therapy.

PMID- 16435599
TI  - [Treatment with statins in general medicine: dosage and effectiveness. Results of
      the observational study STATIMED].
AB  - Using a retrospective study in general medicine, we observed the rates of
      achieving targets for LDL-cholesterol as recommended by the French Agency for the
      Safety of Health care Products (AFSSAPS) in 2000, according to the types of
      statin prescribed and the dosages used. Out of 64 961 individuals treated with a
      statin between 31 July 2001 and 1 August 2002, we identified 22 065 patients
      treated with monotherapy, having had an LDL-cholesterol level performed at least
      6 weeks after starting treatment or after changing statin or dosage, and no
      longer than 6 months before the start of our study in the other cases. In primary
      prevention, 81.9% of patients attained their objectives. The success rates became
      less impressive with increasing levels of cardiovascular risk: 95.6%, 86.9%,
      72.0% and 56.3% for 0, 1, 2 and 3 or more risk factors respectively (p < 0.0001).
      For secondary prevention, the targets were only met for 62.8% of patients. In
      total, only 77.8% of the entire sample met their targets. For each type of
      statin, higher doses were used for patients with higher cardiovascular risk, but
      the percentage of patients reaching their LDL-cholesterol targets diminished. In
      conclusion, under the current conditions of managing lipid risk, the LDL
      cholesterol targets are not sufficiently met. Extrapolating from the data
      obtained in this study, about 300 000 patients in France require better
      management than recommended in the 2000 AFSSAPS guidelines.

PMID- 16435600
TI  - [Propionibacterium acnes infective endocarditis. Study of 11 cases and review of
      literature].
AB  - BACKGROUND: Propionibacterium acnes, a gram positive, anaerobic, skin commensal
      bacillus, is too often considered a biologic fluid contaminant, of blood cultures
      in particular. Its implication has been shown in various infections, including
      brain abscess, ocular infections, osteitis, and acne. It is also the cause of
      infective endocarditis (IE). METHODS: Retrospective, observational study of 11
      patients with P. acnes IE, hospitalised between 1993 and 2001 at the Louis Pradel
      Hospital, Lyon-Bron, and review of 20 published cases. RESULTS: P. acnes IE is
      rare, though its prevalence is probably underestimated. It is most likely to
      affect men (71%), and affects all ages (children 4/31 cases). An entry point,
      probably cutaneous, is rarely confirmed. P. acnes IE often develops on valve
      prosthesis (42%), and embolisms are common (61%). The infective site is usually
      aortic (55%). The often-subtle symptoms and slow growth of the organism in vitro
      complicate the diagnosis, which is often made at a late stage, when valvular and
      peri-valvular destruction has become major. Despite the high sensitivity of P.
      acnes to most antimicrobials, a surgical intervention is very often needed (81%).
      The mortality is relatively high (15% to 27%). Examination of pathologic
      specimens by polymerase chain reaction increases the sensitivity and speed of its
      detection. The identification of P. acnes in a biologic specimen, valvular tissue
      in particular, requires a thorough knowledge of the clinical context before
      concluding to contamination, and mandates close surveillance of the patient. P.
      acnes can be the cause of IE long before it has been detected.

PMID- 16435601
TI  - [Use of the six-minute walk test in cardiology].
AB  - The symptom-limited exercise test is nowadays the gold standard to assess the
      exercise tolerance and the effects of different treatments in patients with
      chronic heart failure (CHF). A simpler alternative to this test is the 6-minute
      walk test. The 6-minute walk test is easy to realize and well-tolerated.
      Moreover, it is reliable just after one familiarization practice and requires
      standardization. Indeed, its conduction, which is submitted to some security
      precautions, can be altered by variation factors. The distance walked during the
      6 minutes was the only parameter studied during the test. This parameter could
      allow judging the CHF severity and prognostic. The analyse of cardiorespiratory
      parameters has shown that the 6-minute walk test relative intensity is near to
      the peak individual values. Moreover, the cardiac and ventilatory adaptation of
      patient during this test depends to his own functional capacity. Lastly, the 6
      minute walk test is a submaximal constant-load exercise, which should be
      performed in complement to the symptom-limited exercise test in cardiac patients.

PMID- 16435602
TI  - [Diagnostic and prognostic value of heart-type fatty acid-binding protein (H
      FABP), an early biochemical marker of myocardial injury].
AB  - Heart-type fatty acid-binding protein (H-FABP) is a 132 amino acids soluble
      protein, with general characteristics resembling myoglobin. Because of its low
      molecular weight (15 kd) and cytoplasmic location, it constitutes a biologic
      marker readily released into the circulation after myocardial injury. Despite the
      development of various immunoassays to measure H-FABP, few are currently easy to
      perform, quantitative and applicable in emergency. Most studies have shown the
      diagnostic sensitivity of H-FABP (i.e. its ability to detect the presence of a
      myocardial infarction) to be high, above that of myoglobin in patients presenting
      within 3 to 6 h of after the onset of chest pain. This superiority is
      attributable to an earlier and more rapid rise in H-FABP than in myoglobin. After
      thrombolysis, the serum concentrations of H-FABP peak at approximately 4 h after
      the onset of chest pain, and return to normal values within 24 h. Because of this
      rapid return of its blood concentration to baseline, H-FABP can contribute to an
      early biologic diagnosis of post-thrombolysis reperfusion and re-infarction. In
      absence of renal insufficiency, H-FABP also provides a reliable estimate of
      infarct size associated with ST segment elevation. When myocardial injury occurs
      after cardiac surgery, the second peak in H-FABP concentration precedes that of
      myoglobin, CK-MB or troponins. In addition, H-FABP peaks earlier and is more
      sensitive than troponins in the detection of subtle myocardial injury in patients
      presenting with acute coronary syndrome without ST segment elevation, and in
      patients with severe heart failure, thus offering early prognostic information.
      Limitations of H-FABP include a limited cardio-specificity, a narrow diagnostic
      window (20 to 30 h), and a nearly exclusive renal elimination.

PMID- 16435603
TI  - [Right bundle branch block: electrocardiographic and prognostic features].
AB  - The electrocardiographic appearances and the significance of right bundle branch
      block were described at the beginning of the 20th century. Typical appearances
      include prolongation > 0.12 s of the QRS complex, RR' or rR' or Rr' appearances
      in V1 and widened S waves in the leads exploring the left ventricle (SI, aVL, V5
      and V6). A delay in the appearance of the intrinsic deflection > 0.08 s may also
      be observed in the right precordial leads and negative T waves with ST depression
      may be seen in V1 and sometimes in V2. Left axis deviation of the QRS complex
      greater than - 45 degrees suggests associated left anterior hemiblock. Right axis
      deviation beyond + 120 degrees is equivocal. The principal differential ECG
      diagnosis is the Brugada syndrome, a familial arrhythmogenic autosomal dominant
      cardiomyopathy of variable penetration. This diagnosis is suggested when ECG
      abnormalities are observed in patients with a personal or family history of
      sudden death. Right bundle branch block only seems to have haemodynamic
      consequences in cardiac failure with associated asynchrony of the left ventricle
      or in certain cases of right ventricular dilatation encountered in congenital
      heart disease. The prognosis of right bundle branch block in the absence of
      underlying cardiac disease is good but it may be poor in other cases,
      particularly coronary artery disease. Moreover, the prognosis of right bundle
      branch block to complete atrioventricular block is rare in the absence of
      associated cardiac disease.

PMID- 16435605
TI  - Cardiac myocyte neuronal nitric oxide synthase. New therapeutic target in heart
      failure?
AB  - Although nitric oxide-dependent regulation of contractile function is altered in
      the diseased and failing heart, several aspects of nitric oxide (NO) signalling
      in the myocardium remain poorly understood. Some apparently contrasting findings
      may have arisen from the use of non-isoform-specific inhibitors of NO synthase
      isoforms (NOS) as compared to the use of mouse models genetically deficient or
      overexpressing the NOS thought to be responsible for the increase in NO
      production in heart failure (mainly NOS2 and NOS3). In recent years,
      identification of the neuronal NOS (NOS1) isoform in cardiac myocytes and the
      recognition of the importance of its subcellular localisation have greatly
      advanced the understanding of the critical role of NOS1-derived NO in the control
      of myocardial contractility both in the normal and failing heart. The challenge
      is now to confirm these emerging findings on the critical role of NOS1-derived NO
      in human cardiac physiology and hopefully translate them into therapy.

PMID- 16435604
TI  - Phospholamban: a key determinant of cardiac function and dysfunction.
AB  - Our knowledge and understanding of the normal and diseased heart has advanced
      significantly over the past decade. Evidence indicates that several signaling
      pathways involved in the induction of cardiac disease and heart failure are
      associated with abnormal calcium handling by the sarcoplasmic reticulum proteins:
      calcium-ATPase pump and phospholamban. Indeed, the failing heart is characterized
      by impaired removal of cytosolic calcium, reduced loading of the cardiac
      sarcoplasmic reticulum, and defective calcium release, culminating in impairment
      of cardiac diastolic and systolic function. This review summarizes studies which
      highlight the key role of the sarcoplasmic reticulum proteins, calcium-ATPase
      pump and phospholamban, in the regulation of cardiac function; the significance
      of the phospholamban interaction with the calcium-ATPase pump through transgenic
      animal models; the recent findings of the inhbitor-1 of protein phosphatase-1 as
      a new potential therapeutic agent in heart failure; and finally, the discoveries
      of human phospholamban mutations leading to disease states.

PMID- 16435606
TI  - Positron emission and computed tomographies in cardiology.
AB  - Predicting acute vascular events in vulnerable patients requires new strategies:
      biomarkers and imaging are among the major options. Adding perfusion and
      viability data to anatomical informations with MRI, isotopes or MSCT, will
      dramatically impact on our decisions to diagnose atherosclerotic patients. The
      present combination of MSCT scanners with PET or conventional scintigraphy
      enlarges capabilities of calcium scoring and coronary angiography to perfusion
      imaging. But MSCT alone, easy, accurate and conspicuous, already changed the face
      of daily practice in cardiology. Screening of very high risk populations and
      plaque imaging now are under clinical investigations.

PMID- 16435607
TI  - [Factor VIII hyperactivity: an arterio-venous thrombogenic factor. Case report].
AB  - Thrombosis is the principal mechanism in vascular pathology, whether cerebral,
      coronary or peripheral. During the initial stages of infarction, coagulation
      contributes to vascular occlusion, the haemostatic factors playing a determining
      role in the development of atherothrombotic lesions. An increase in a coagulation
      protein, besides any lowering of anticoagulation protein levels, is a risk factor
      for thrombosis. Among these pro-coagulant factors, the pro-thrombogenic action of
      factor VIII has without doubt been studied the least. We report the case of a 62
      year old patient with a personal and family history of many previous thrombotic
      episodes, both arterial and venous, in whom factor VIII hyperactivity was
      discovered after a myocardial infarction. This case underlines the association of
      the factor VIII complex with thrombosis, and its clinical repercussions,
      especially the incidence of coronary pathology.

PMID- 16435608
TI  - [Ablation of ventricular extra-systole in the left Valsalva sinus. A case
      report].
AB  - We report the case of a patient presenting with unrelenting isolated or
      repetitive monomorphic ventricular extra-systoles, with left block and right axis
      deviation, which appeared to arise from the right ventricular chamber, but for
      which ablation was finally performed in the left Valsalva sinus. The ECG and
      endocavity electro-physiological features which led us to suspect this atypical,
      although not exceptional, situation are reported, as well as the techniques for
      ablation available in this case.

PMID- 16435610
TI  - [About: pleiotropic effects of statins in atherosclerosis].

PMID- 16435611
TI  - [CRASH-2: the Clinical Randomization of an Antifibrinolytic in Significant
      Haemorrhage trial].

PMID- 16435612
TI  - [Anesthesia in the doctor's office].

PMID- 16435613
TI  - [Metabolic and immune response to spinal vs intravenous morphine for analgesia
      after radical prostatectomy].
AB  - OBJECTIVE: To study differences between the endocrine-metabolic and immune cell
      responses to spinal or intravenous administration of morphine for analgesia after
      radical prostatectomy. MATERIAL AND METHODS: Prospective study of 60 patients
      randomized to 2 groups: in group A (n=30) morphine for postoperative analgesia
      was infused intravenously and in group B (n=30) morphine was infused into the
      spinal canal. Changes in leukocyte populations and lymphocyte subpopulations in
      peripheral blood and blood from surgical drains (local) were analyzed to study
      immune cell response to morphine administration. Cortisol, corticotropin, growth
      hormone, glucose, and immunoglobulin levels in peripheral blood were measured as
      indicators of metabolic and humoral immune responses. RESULTS: Both groups
      developed lymphopenia in peripheral blood. The group treated with spinal morphine
      had significantly lower CD4+ cell counts in peripheral blood P<0.05. No
      differences were found in the local leukocyte response in either group.
      Significant differences were found in natural killer and CD4+ cell counts both
      locally and in peripheral blood P<0.05. There was humoral immune response
      suppression in both groups; however, it was more marked in the group treated with
      spinal morphine and the difference was significant P<0.05. The metabolic response
      was greater in the group treated with intravenous morphine. CONCLUSION: Patients
      who received morphine by spinal infusion had a less marked endocrine-metabolic
      response. Although local cell responses were similar in the 2 groups, the
      response in peripheral blood was different, possibly reflecting different
      mechanisms of central modulation of the inflammatory response to stress.

PMID- 16435614
TI  - [Upper respiratory tract infections in children: impact on surgical scheduling at
      a pediatric hospital].
AB  - OBJECTIVE: To determine the rate of cancelation of scheduled surgical procedures
      attributable to upper respiratory tract infection (URTI) in our university
      pediatric hospital in Madrid and to analyze the effect that literature reviews
      and appropriate counseling of parents would have on cancelations. MATERIAL AND
      METHODS: We carried out a retrospective study of the reasons for canceling
      scheduled pediatric ear, nose, or throat operations in 2001, 2002, 2003, and
      2004. Statistical comparisons were performed with the chi2 test. RESULTS: In
      2001, 24% of the 641 procedures scheduled were canceled, 12.9% of them because of
      URTIs. After applying criteria based on a review of the literature, 15% of the
      751 procedures were canceled in 2002, 4.9% of them because of URTIs (P<0.0001 in
      comparison with 2001). In 2003 14.3% of the 760 scheduled procedures were
      canceled, 6.5% because of URTIs (P<0.0001 in the comparison with 2001). In 2004
      12.2% of the 692 scheduled procedures were canceled, 7.2% because of URTIs
      (P<0.0001 in comparison with 2001). Cancelations in autumn-winter or in spring
      summer seasons amounted to 28.2% vs 19.8% in 2001, 17.1% vs 12.7% in 2002, 16.6%
      vs 11.8% in 2003, and 13.8% vs 11.1% in 2004. CONCLUSIONS: URTIs are responsible
      for a high rate of cancelations of scheduled operations, particularly in colder
      seasons of the year. To obtain optimal results, criteria based on up-to-date
      literature reviews should be put into effect and parents should be given
      appropriate information.

PMID- 16435615
TI  - [Intradural ropivacaine for cesarean section: choosing the appropriate dose].
AB  - The trend in spinal administration of local anesthetics is to use small doses.
      The aim of this study was to compare 2 minimum doses of ropivacaine administered
      by intradural infusion for cesarean section. MATERIAL AND METHODS: After the
      study was approved by the ethics committee, 64 women scheduled for cesarean
      delivery were enrolled. The patients were randomly allocated to 2 groups: a group
      of 32 women received 7.5 mg of 0.75% ropivacaine (ROP 0.75%) and another group of
      32 received 10 mg of the anesthetic at a concentration of 1% (ROP 1%). Both
      groups received 25 microg of fentanyl. Parameters assessed were time until the
      block reached T6, time until the highest point was reached, hemodynamic changes,
      incidence rates of hypertension and bradycardia, ephedrine and atropine
      requirements, time until recovery of motor function, duration of analgesia, time
      until regression of block to T10, degree of muscle relaxation, patient
      satisfaction, and incidence of adverse side effects. RESULTS: No patients were
      excluded from the study. It was necessary to provide a rescue dose in 16% of the
      cases in the ROP 0.75% group (P<0.05). The incidence of hypotension was higher in
      the ROP 1% group than in the lower-dose group (60% vs 28%) and ephedrine
      requirements were greater (16.56 [SD, 18.85] vs 7.96 [15.44] mg; P<0.05 in both
      cases). There were no significant differences in other parameters. CONCLUSION:
      There was greater need for a supplementary dose of local anesthetic and a lower
      incidence of hypotension in the ROP 0.75% group. The level of anesthesia was
      satisfactory for all patients in the ROP 1% group but the incidence of
      hypotension was higher.

PMID- 16435617
TI  - [Perioperative use of beta-blockers in noncardiac surgery].
AB  - A variety of strategies have been used to reduce the high prevalence and
      mortality rates of cardiac complications in patients undergoing noncardiac
      surgery. One approach taken is to prescribe agents that block beta-adrenergic
      receptors. The effect of beta-blockers on myocardial ischemia is multifactorial:
      they correct myocardial oxygen imbalance, prevent rupture of atheromatous plaque,
      and reduce coronary vasoconstriction. We summarize the results of several
      recently published studies that confirm the beneficial effects and the low
      incidence of side effects.

PMID- 16435616
TI  - [Office-based anesthesia: consensus report. Sociedad Espanola de Anestesiologia y
      Reanimacion. 2005].

PMID- 16435618
TI  - [Thoracic impedance cardiography in a case of anomalous drainage of the superior
      vena cava into the coronary sinus].
AB  - Thoracic impedance cardiography is a noninvasive hemodynamic monitoring technique
      based on the physical principal of impedance, which can be defined as resistance
      to electrical flow. We report the case of a man who underwent orthotopic heart
      transplantation, during which the superior vena cava was found to drain into the
      coronary sinus. Impedance cardiography was used because hemodynamics could not be
      monitored invasively with a Swan-Ganz catheter. We describe the main applications
      of impedance cardiography and the characteristics of this rare vascular anomaly.

PMID- 16435620
TI  - [Late mediastinitis with bilateral hydrothorax after vessel perforation by a
      central venous catheter].
AB  - A central venous catheter was inserted into the right internal jugular vein of a
      67-year-old woman to provide parenteral nutrition on the 7th day after surgery.
      Five days later, mediastinitis with bilateral hydrothorax had developed and was
      causing respiratory failure and systemic inflammatory response syndrome secondary
      to documented vascular perforation by the catheter. Four factors have been
      associated with increased risk of perforation: catheter rigidity and diameter,
      the angle between the tip of the catheter and the vessel wall, and insertion from
      the left. Three catheter positions have been described as safe when
      radiologically confirmed: the superior vena cava, the point where the superior
      vena cava meets the atrium, and the midpoint of the innominate vein. However, it
      should not be forgotten that a radiograph is 2-dimensional and a single image of
      a catheter tip can correspond to a variety of locations (superior vena cava, vena
      innominata, extravascular location, and more). Even when there is clinical and
      radiologic evidence of catheter positioning, vascular perforation should be
      suspected in patients with a central venous catheter and bilateral pleural
      effusion who present respiratory insufficiency and hemodynamic instability.

PMID- 16435619
TI  - [Patient with right ventricular arrhythmogenic dysplasia, ascites and ulcerative
      colitis: anesthetic management during major abdominal surgery].
AB  - A 43-year-old man with ulcerative colitis was scheduled for pancolectomy owing to
      adenomatous transformation of polyps. The patient had right ventricular
      arrhythmogenic dysplasia, with deteriorating ventricular function, and carried an
      automatic implantable defibrillator. We discuss the general features of
      arrhythmogenic right ventricular dysplasia and its implications for management
      and monitoring during major abdominal surgery. Perioperative management of a
      patient with an implantable defibrillator is also discussed, with special
      attention to the influence of electromagnetic interference that can affect how
      the device functions during surgery. Finally, we list signs that should lead to
      suspicion of arrhythmogenic right ventricular dysplasia in an asymptomatic
      patient.

PMID- 16435621
TI  - [Airway fire during electrocautery dissection of the tonsils].

PMID- 16435622
TI  - [Activated recombinant factor VII for bleeding after a kidney transplant].

PMID- 16435623
TI  - [Syringomyelia and Chiari type 1 malformation with associated bilateral vocal
      cord paralysis and obstructive sleep apnea syndrome].

PMID- 16435624
TI  - [Posterior lumbar plexus and gluteal sciatic nerve blocks for a femoropopliteal
      bypass operation in a patient with cardiogenic shock].

PMID- 16435625
TI  - [Massive subcutaneous emphysema involving perimuscular tissue in laparoscopic
      surgery on the colon].

PMID- 16435626
TI  - [Subdural block complicating epidural analgesia].

PMID- 16435627
TI  - [Entropy monitoring of electroencephalographic silence during cessation of blood
      circulation in deep hypothermia].

PMID- 16435628
TI  - [Obstetric epidural analgesia in Hospital Universitario Central in Asturias,
      Spain, 2001-2004].

PMID- 16435629
TI  - Epidural analgesia, maternal fever and neonatal well being.

PMID- 16435630
TI  - [Radiograph of a Bochdalek hernia].

PMID- 16435631
TI  - Hurricane Katrina--pediatric dentistry's response.

PMID- 16435632
TI  - An American disaster.

PMID- 16435633
TI  - Twenty-four years later and things are changing...some good, some not.

PMID- 16435634
TI  - Tooth whitening in children and adolescents: a literature review.
AB  - The purpose of this paper was to summarize the findings of a literature review on
      the use of peroxide-based tooth-whitening agents in children and adolescents.
      Safety considerations, including localized adverse effects and toxicological
      concerns, are described. Oral findings include: (1) 1 in every 2 to 3 patients
      may experience tooth sensitivity and/or gingival irritation after bleaching
      treatment, which may be more traumatic an experience for children than adults;
      (2) depending on dose, duration, frequency, and route, studies indicate excessive
      exposure to peroxide can be potentially harmful; (3) degree of potential toxicity
      and harmful outcomes increases in those who overuse whiteners--a concern in
      teenagers; (4) careful case selection using stringent criteria is suggested for
      primary teeth whitening; (5) whitening in healthy adolescents is a case-by-case
      determination that must include the weighing of risks (oral health and age) vs
      benefits (improved esthetic perception). It is hoped that the present review will
      lead to a better understanding of the health implications of tooth whitening in
      children and adolescents, and offer guidance for treatment that provides
      satisfactory outcomes externally (enamel and gingiva) and internally (endodontic
      tissues and systemic health).

PMID- 16435635
TI  - Nonnutritive sucking habits and anterior open bite in Brazilian children: a
      longitudinal study.
AB  - PURPOSE: The purpose of this longitudinal study was to assess the relationship
      between nonnutritive sucking habits and anterior open bite in 305 4- to 5-year
      old children attending state schools in the city of Recife, Brazil. METHODS: The
      data were collected by interviewing the children's mothers or guardians and
      through clinical examinations carried out by 1 calibrated examiner (K = 1).
      Bivariate analyses (Pearson chi-square, McNemar, and Stuart-Maxwell tests) were
      used for the statistical analysis. RESULTS: The prevalence of sucking habits was
      low, and the sample showed reductions after 1 year of follow-up. The prevalence
      of anterior open bite decreased from 33% to 29% after 1 year. A significant
      association was found between anterior open bite and sucking habits. Open bite
      self-correction was associated with the abandoning of deleterious habits.
      CONCLUSIONS: The low prevalence of nonnutritive sucking habits and its reduction
      during the period studied seem to reflect a natural tendency in preschool
      children. Even presenting a slight reduction, the high prevalence of anterior
      open bite draws attention to the importance of longitudinal studies to support
      scientific evidences for early clinical intervention.

PMID- 16435636
TI  - A study of primary dental enamel from preterm and full-term children using light
      and scanning electron microscopy.
AB  - PURPOSE: The aim of this study was to examine the enamel thickness of the
      maxillary primary incisors of preterm children with very low birth weight (<
      1,500 g) compared to full-term children with normal birth weight. METHODS: A
      total of 90 exfoliated maxillary primary central incisors were investigated using
      light microscopy and scanning electron microscopy (SEM). Three serial
      buccolingual ground sections of each tooth were examined under light microscopy,
      and maximum dimensions of the prenatally and postnatally formed enamel were
      measured. RESULTS: The enamel of preterm teeth was approximately 20% thinner than
      that for full-term teeth. Most of the reduction was observed in the prenatally
      formed enamel. This was 5 to 13 times thinner than that for full-term children
      (P<.001). The "catch-up" thickness of postnatally formed enamel did not
      compensate fully for the decrease in prenatal enamel (P<.001). Although none of
      the teeth used in this study had enamel defects visible to the naked eye, 52% of
      preterm teeth showed enamel hypoplasia under SEM, compared with only 16% found on
      full-term teeth (P<.001). These defects were present as pits or irregular,
      shallow areas of missing enamel. CONCLUSIONS: Preterm primary dental enamel is
      abnormal in surface quality, and is significantly thinner compared to full-term
      enamel. The thinner enamel is due mainly to reduced prenatal growth and results
      in smaller dimensions of the primary dentition.

PMID- 16435637
TI  - Effects of a positive verbal presentation on parental acceptance of passive
      medical stabilization for the dental treatment of young children.
AB  - PURPOSE: The purpose of this study was to investigate the impact of a positive
      verbal presentation on parental acceptance of passive medical stabilization of
      young dental patients needing dental treatment in the private setting. METHODS:
      Parents appearing for the treatment of their young, uncooperative child were
      informed regarding the use of passive medical stabilization (Papoose Board). The
      control group (CG) was given a neutral explanation regarding the use of the
      Papoose Board (PB), and the experimental group (EG) was given a positive verbal
      presentation. A video film depicting 2 children undergoing dental treatment with
      conscious sedation and PB and a third child undergoing dental treatment under
      general anesthesia was viewed. Next, a post-screening survey regarding parents'
      attitudes to the treatment modalities was given. RESULTS: Sixty parents completed
      the trial. EG parents were found to be significantly more receptive to PB use
      compared to CG parents (69% vs 10%; chi-squared = 19.48; P=.001). CG parents
      believed that active restraint by a parent would be just as successful as passive
      restraint. The majority of EG parents, however, voiced the opposite opinion. EG
      parents attributed a restrained child's crying while in a PB to the child's fear,
      while CG parents attributed it directly to the restraint. CONCLUSIONS: Parental
      acceptability of the PB, coupled with conscious sedation, is dependent on the way
      it is presented by the clinician. Positive explanation may result in more
      parents' acceptance of this form of treatment.

PMID- 16435638
TI  - Dental treatment of a child with Rubinstein-Taybi syndrome.
AB  - Rubinstein-Taybi syndrome (RTS) is a human genetic disorder characterized by
      mental retardation and physical abnormalities including broad thumbs, big and
      broad toes, short stature, and craniofacial anomalies. The oral manifestations
      include small oral opening, pouting lower lip, retro/micrognathia. and higher
      arched, narrow palate. The purpose of this case report was to demonstrate the
      complicated dental treatment of a 12-year-old, developmentally disabled girl,
      living with a foster family, who suffered from RTS, extensive caries, and very
      poor oral hygiene. The patient demonstrated total lack of cooperation. The dental
      treatment had been carried out under general anesthesia (GA). Possible problems
      during GA in such patients are described. Fiberoptic video-assisted bronchoscope
      was prepared for the GA in case of airway emergency and/or difficult intubation.
      The GA process was uneventful, despite the extensive treatment delivered to the
      patient. Prospects for future good oral and dental status in this patient are
      questionable because of her extreme lack of cooperation.

PMID- 16435639
TI  - Taurodontism and learning disabilities in patients with Klinefelter syndrome.
AB  - PURPOSE: The purpose of this descriptive clinical study was to determine the
      prevalence rates of taurodontism and learning disabilities in a sample of
      patients with Klinefelter syndrome. METHODS: Questionnaires and dental
      radiographs of Klinefelter syndrome patients were obtained and analyzed using
      previously published methods. Prevalence rates were determined for taurodontism
      and learning disabilities in the sample population and compared to the general
      population. Statistical analyses included a Fisher's exact 2-sided test to
      compare the prevalence rates to that found in the general population and
      subsequent determination of the positive predictive value. RESULTS: Taurodontism
      was found in 75% of the 24 participants. Eighty-three percent of the participants
      reported having a learning disability. These rates are significantly higher than
      the general population, as reported in the literature. CONCLUSIONS: The positive
      predictive value for Klinefelter syndrome, given a male patient with taurodontism
      and a learning disability, is 84%. In this case, the dentist should recommend
      karyotyping to the patient, parent, or physician. This demonstrates how important
      it is for dentists to understand and assist physicians in the diagnosis of
      genetic disorders.

PMID- 16435640
TI  - A comparison of two meperidine/hydroxyzine sedation regimens for the
      uncooperative pediatric dental patient.
AB  - PURPOSE: The purpose of this study was to compare the safety and efficacy of
      submucosal-administered meperidine (SM) and oral-administered meperidine (OM).
      Both regimens were used in conjunction with oral hydroxyzine for the sedation of
      children for dental treatment. METHODS: Twenty preschool-age children, with
      previous histories of uncooperative behavior, were randomly assigned to first
      receive a sedation regimen of either SM (0.5 mg/ lb), or OM (1 mg/lb), both with
      oral hydroxyzine (0.5 mg/lb). A cross-over design was utilized so that each child
      received both regimens. Safety was monitored through vital signs and side
      effects. Efficacy was measured with Houpt and Frankl behavior ratings. RESULTS:
      Vital signs remained stable during both treatments. Differences noted were
      clinically insignificant. The major side effects reported during submucosal
      injection included pain (58%) and edema (26%). All blinded behavior ratings, in
      both sedation regimens, significantly improved from presedation Frankl ratings.
      No significant differences existed between treatments. Success was 63% in the SM
      group and 80% in the OM group. The percentages were not statistically significant
      (P=.219). CONCLUSIONS: Both methods of administration were found to be safe and
      effective for sedating uncooperative pediatric dental patients. Neither was
      significantly more effective or safer than the other.

PMID- 16435641
TI  - Comparison of drops versus spray administration of intranasal midazolam in two-
      and three-year-old children for dental sedation.
AB  - PURPOSE: The purpose of this retrospective record review of 2- and 3-year-old
      dental patients receiving intranasal midazolam (INM) was to compare drops vs
      spray administration to behavioral outcomes observed for agent acceptance during
      administration and for agent efficacy during parental separation, local
      anesthesia injection, and delivery of restorative dentistry. METHODS: Temperament
      and attachment scores based on adaptability and approachability determinants
      judged by the parent and interactive and Frankl behavior rating scores determined
      by the operator were used to compare preoperative behavioral characteristics
      between the 2 groups. The Ohio State Behavioral Rating Scale (OSBRS) and the
      Frankl behavior rating scale were used to determine intraoperative behavioral
      outcomes for agent acceptance and efficacy. RESULTS: Analysis of 64 sedation
      records revealed that the 2 groups had similar preoperative behavioral
      characteristics. Improvements in the Frankl behavioral rating scores were
      observed during the sedation, but no statistically significant difference between
      the drops and spray groups was measured using the OSBRS. For the procedural event
      of drug administration, however, the spray group demonstrated a statistically
      significant reduction (P=.025) in aversive behaviors when compared to drops
      administration as measured by the OSBRS. This finding was observed, even though
      the volume of spray was greater than used in the drops group. CONCLUSIONS: Spray
      administration of INM produced significantly less aversive behavior than
      administering drops in 2- to 3-year-old dental patients of similar behavioral
      characteristics. The effectiveness of the conscious sedation technique was not
      influenced by the method of nasal administration. This study suggested that the
      use of a commercially available atomizer improved patient acceptance of INM
      administration but did not influence agent efficacy compared to drops
      administration for 2- to 3-year-old dental patients in an office setting.

PMID- 16435642
TI  - An evaluation of pediatric dental patient education materials using contemporary
      health literacy measures.
AB  - PURPOSE: The purpose of this study was to determine the appropriateness of
      nationally available dental information materials according to the suitability
      assessment of materials (SAM) method. METHODS: Clinically related, professionally
      produced patient dental health education materials (N=22) provided by the
      American Academy of Pediatric Dentistry (AAPD) were evaluated using the SAM
      method that had previously been judged valid and reliable. A rater was trained by
      an experienced health literacy evaluator to establish validity. The rater then
      rated all materials for 5 categories of assessment (content, literacy demand,
      graphics, layout and typography, and learning stimulation/motivation) and an
      overall assessment, and repeated 5 materials to establish intrarater reliability.
      RESULTS: When compared to the experienced rater, the validity was K=0.43. The
      reliability was established for all ratings as K=0.52. The consistently weakest
      categories were content, graphics, and learning stimulation, while reading level
      as part of literacy demand was often not suitable. The overall suitability of the
      AAPD materials was generally classified as superior. CONCLUSIONS: Reliable and
      valid evaluation of available dental patient information materials can be
      accomplished. The materials were largely superior. There is great variability
      within the categories of evaluation. The categories of content, graphics, and
      learning stimulation require attention and could raise the overall quality of the
      materials.

PMID- 16435643
TI  - Access and utilization of dental services by Alabama Medicaid-enrolled children:
      a parent perspective.
AB  - PURPOSE: The purposes of this survey were to assess barriers to utilization of
      dental services among Medicaid-enrolled Alabama children and identify families
      who used or did not use Medicaid-covered dental services. METHODS: A random
      sample of 4,500 parents of Medicaid-eligible children ages 3 to 19 years was
      surveyed. Participants came from Medicaid enrollment data stratified by area of
      residence into 3 groups: (1) large urban; (2) town; and (3) rural. Univariate and
      multivariate analyses were conducted. RESULTS: The overall response rate was 40%
      (N = 1,766). Most respondents (71%) reported that their child had a dental visit
      in the past year. Compared to parents who had a dental visit, those who reported
      no visits were more likely to: (1) be non-Hispanic African American; (2) be less
      educated; (3) live in rural settings of Alabama; (4) have more children younger
      than 6 or older than 12; (5) have more children with disabling conditions; and
      (6) report poor perceived oral health. Respondents with no dental visits were
      grouped into 3 categories-those who: (1) believed they did not need dental care
      (46%); (2) thought dental care was hard to find (34%); and (3) tried but could
      not get dental care (20%). The first group had significantly less respondents
      with a high school or greater education, more reporting perceived good to
      excellent oral health, and more living in rural areas, compared to the other 2
      groups. CONCLUSIONS: Families who did not use Medicaid-covered dental services
      include: (1) a group with high perceived need and barriers to care; and (2) a
      group with little perceived need. Interventions must target both groups.

PMID- 16435644
TI  - Reliability and validity of brief measures of oral health-related knowledge,
      fatalism, and self-efficacy in mothers of African American children.
AB  - PURPOSE: Low-income African American children experience high rates of dental
      caries compared to the general population. Knowledgeable and efficacious
      caregivers can play an important role in caries prevention. The purpose of this
      study was to develop and evaluate 4 brief measures reflecting mothers'
      potentially modifiable cognitions associated with African American children's
      oral health: (1) knowledge about appropriate bottle use (KBU); (2) knowledge
      about children's oral hygiene (KCOH); (3) oral health-related fatalism (OHF); and
      (4) oral health-related self-efficacy (OHSE). METHODS: Questions were selected
      based on reviews of the health promotion and oral health literature, with input
      from low-income African American caregivers of young children. Reliability and
      validity were evaluated using survey and dental examination data from 719 low
      income African American mothers and their 1- to 5-year-old children. RESULTS:
      Alpha reliabilities ranged from 0.76 to 0.91. KCOH was significantly associated
      with mothers' oral health perceptions and children's caries status. OHSE was
      significantly positively correlated with children's brushing frequency and with
      mothers' subjective perceptions of children's oral health, which was, in turn,
      significantly associated with children's caries status. CONCLUSIONS: Results
      support the reliability and validity of the new measures. If confirmed by further
      research, these measures can be used to develop tailored educational and
      cognitive-behavioral interventions to reduce oral health disparities.

PMID- 16435645
TI  - Carolina in the Carolines: a survey of patterns and meanings of smoking on a
      Micronesian island.
AB  - Tobacco use--especially smoking industrially manufactured cigarettes--kills
      nearly 5 million people annually and is the leading preventable cause of death
      worldwide. Tobacco is a widely used global commodity embedded in cultural
      meanings, and its consumption involves a set of learned, patterned social
      behaviors. Seemingly, then, tobacco offers a most appealing anthropological
      research topic, yet its study has been relatively ignored by medical
      anthropologists when compared to research on alcoholic beverages and illegal
      drugs. To help fill this gap, this article sketches the historical background of
      tobacco in Micronesia, presents the results of a cross-sectional smoking survey
      from Namoluk Atoll, and describes contemporary smoking patterns and locally
      understood symbolic associations of tobacco. Intersections among history, gender,
      local meanings, the health transition, and the transnational marketing of tobacco
      are addressed, and cigarette smoking is seen as part of a new syndemic of chronic
      diseases in Micronesia.

PMID- 16435646
TI  - Partner notification methods for African American men being treated for
      trichomoniasis: a consideration of main men, Second Hitters, and Third Players.
AB  - This pilot study sought information on African American men's preferences for
      partner notification methods for a common sexually transmitted infection called
      trichomoniasis. Two focus groups of African American men were convened at a
      public STI clinic where they were being treated for trichomoniasis. The groups
      identified a sexual hierarchy in men's preferences for methods of partner
      notification. The hierarchy consisted of main men (Cake Daddies), second men
      (Second Hitters), and third or fourth men (Third Players), with placement
      depending on age, income, and social status. Health department employees affirmed
      the existence of a sexual hierarchy in a separate focus group. Sexual and
      economic bartering formed the basis of the hierarchy, and the secrecy involved in
      such arrangements presented a considerable challenge for STI control. Disease
      intervention specialists who were responsible for contact tracing spoke of cat
      and-mouse methods in contacting the men without understanding fully exactly how
      the hierarchy influenced men's responses to partner notification. The findings
      suggest that STI control efforts must take the sexual hierarchy and its privacy
      implications into account if partner notification methods are to be acceptable to
      African American men.

PMID- 16435647
TI  - "Taming tradition": medicalized female genital practices in western Kenya.
AB  - This article considers the question of female genital practices at the hands of
      health workers in western Kenya. Recent articles in Medical Anthropology
      Quarterly have critically engaged with the biomedical arguments condemning such
      practices. This article studies the case of medicalized circumcision in which
      biomedical concerns over health risks have become incorporated in their
      vernacular practice. Although some suggest that medicalization may provide a harm
      reduction strategy to the abandonment of the practice, research in one region
      challenges this suggestion. It argues that changing and conflicting ideologies of
      gender and sexuality have led young women to seek their own meaning through
      medicalized practice. Moreover, attributing this practice to financial
      motivations of health workers overlooks the way in which these "moral agents"
      must be situated within their social and cultural universe. Together, these
      insights challenge the view that medicine can remain neutral in the mediation of
      tradition.

PMID- 16435648
TI  - A room for reflection: self-observation and transformation in participatory HIV
      prevention work.
AB  - This article looks at HIV prevention projects in which established stigmatized
      and stigmatizing roles were actively reversed and manipulated in pursuit of HIV
      harm reduction. In two Norwegian projects, sex workers and drug users carried out
      harm-reduction activities with other drug users and sex workers. Although HIV
      related harm reduction was the aim of the projects, termination or reduction of
      drug use or sex work was not. Such changes nevertheless occurred among the sex
      workers and drug users who took active part in the project. The article considers
      these changes in order to reflect on the meanings and roles of participation in
      HIV prevention work. In particular, the discussion theorizes on possible ways in
      which alteration of roles and subject positions may produce self-reflective
      effects with transformative potentials.

PMID- 16435650
TI  - Effective child welfare practice with immigrant and refugee children and their
      families.
AB  - This article presents a multistage migration framework to broaden the lens
      through which child welfare personnel can view immigrant and refugee families and
      their children. By better understanding the family's experiences in both
      emigration and immigration, including reasons for leaving their home country,
      experiences in transit, and reception and resettlement experiences in the United
      States, child welfare personnel are better equipped to assess their needs and
      provide effective prevention, protection, permanency, and family preservation
      services. Case examples illustrating the application of the framework and
      guidelines for program and practice are included.

PMID- 16435651
TI  - Assessment of issues facing immigrant and refugee families.
AB  - This article identifies the different problems immigrants and refugees face in
      the United States, especially socioeconomic and psychosocial concerns that often
      relate to the experience of migration. Traditional familial roles and
      responsibilities are frequently challenged, exacerbated by sociocultural
      differences and inadequate understandings between the new arrivals and the host
      country. Essential in assessments of immigrant and refugee families is evaluating
      resources for social, economic, and cultural integration; discriminating between
      realistic and unrealistic expectations; evaluating families' problem-solving
      abilities; exploring family functioning within the context of heritage;
      identifying the transferability of work skills; and gauging families' learning
      capabilities and motivation for adaptation.

PMID- 16435652
TI  - Parenting and the process of migration: possibilities within South Asian
      families.
AB  - The migration experience creates a unique set of challenges for families, which
      can result in intergenerational conflict and create the conditions for abuse or
      neglect. Alternatively, families can cope with these challenges in creative and
      seemingly contradictory ways, thus strengthening family relationships. This
      article introduces the process of migration as a theoretical framework to use in
      understanding the complexity of the migration experience as well as the wide
      range of coping responses within families. The process was developed as a
      theoretical tool in an ethnographic study of first- and second-generation South
      Asian women in the United States; the study's findings are used to illustrate the
      application of the process to South Asian parenting experiences and show how the
      process of migration-where families adjust to a different set of structural
      conditions, ideologies, cultural norms, and social systems-shapes parenting and
      family life.

PMID- 16435653
TI  - Social work with Bosnian Muslim refugee children and families: a review of the
      literature.
AB  - More than two million Bosnian Muslims were ethnically cleansed in the Balkan
      region; of these, 200,000 were killed while the others were forced to flee their
      homes and become refugees. This article focuses on the influence of societal and
      cultural values coupled with wartime experiences on the transition of Bosnian
      refugee families to their new countries. Consideration is given to culturally
      competent theoretical frameworks and practice principles social workers can use
      to assist Bosnian Muslim children and families in their adaptation process within
      their resettlement communities.

PMID- 16435654
TI  - Sudanese refugee youth in foster care: the "lost boys" in America.
AB  - This study examined the resettlement experiences of unaccompanied Sudanese
      refugee youth placed in foster care from the perspectives of the youth, foster
      parents, and agency caseworkers. Youth experienced considerable success. The
      challenges of adjusting to school and family life, however, suggest a need for
      funding to support more intensive educational services, more cultural training
      and support for foster parents and school personnel, and flexibility to provide
      services in more culturally appropriate modalities.

PMID- 16435655
TI  - Finding the bicultural balance: immigrant Latino mothers raising "American"
      adolescents.
AB  - This article discusses the cross-cultural issues that confront immigrant Latino
      parents living and raising adolescents in the United States. Emphasis is placed
      on the need for social work practitioners, who, as they aid a family's
      integration into mainstream society, will listen to the parents' concerns and
      incorporate their past experiences and traditional culture into the assessment
      and treatment processes. Implications for practice, programs, and policy are also
      discussed.

PMID- 16435656
TI  - Working together as culture brokers by building trusting alliances with bilingual
      and bicultural newcomer paraprofessionals.
AB  - The authors' reflect on the challenges and rewards of partnering as casework
      supervisors with bilingual and bicultural newcomer paraprofessionals in
      resettlement work with refugee youth. Such individuals are generally recruited
      for their linguistic abilities and cultural knowledge, but they can lack formal
      clinical training or licensing credentials. Drawing on their own experience as
      supervisors of bilingual and bicultural newcomer paraprofessionals from Cambodia,
      Laos, and Vietnam, the authors compare their early attempts to establish trust
      and communication with insights gained in more recent supervisory experiences.
      Recommendations are offered that promote mutual understanding between newcomer
      paraprofessionals and their Western-trained supervisors.

PMID- 16435657
TI  - Cultural competence in the assessment of poor Mexican families in the rural
      southeastern United States.
AB  - Increasing numbers of poor Mexican immigrant families are settling in the rural
      southeastern United States. Most of these families are from isolated agrarian
      communities in Mexico and are headed by unskilled laborers or displaced farm
      workers with little education. Child welfare workers and other service providers
      in rural communities may be poorly prepared to address the needs of this
      population. This article provides an overview of the cultural, social, and family
      dynamics of first generation, working class Mexicans to promote cultural
      competency among helping professionals. An ecological perspective is used to
      examine the strengths that poor Mexicans bring from their culture of origin,
      stresses of the migratory experience and ongoing adaptation, shifts that may
      occur in family structure and functioning, disruptions in the family life cycle,
      the role of social supports in family adaptation, and effect of institutional
      discrimination on family well-being. Suggestions also are made for essential
      components of adequate in-service education.

PMID- 16435658
TI  - Serving immigrant families and children in New York City's child welfare system.
AB  - This article describes the efforts and special initiatives of New York City's
      Administration for Children's Services to improve services to immigrant and
      English language learner populations. Children's Services convened an immigration
      issues advisory subcommittee, created special tools for child welfare staff,
      collaborated with legal agencies to assist foster children with immigration
      status adjustments, improved agency data collection, and launched an agency-wide
      training initiative on immigration issues. The challenges encountered by
      Children's Services offer important insight for child welfare agencies in other
      jurisdictions designing strategies to strengthen their services for immigrant
      communities.

PMID- 16435659
TI  - The Call-Centre: a child welfare liaison program with immigrant serving agencies.
AB  - Alberta, Canada, welcomed nearly 16,000 landed immigrants in 2003, of whom more
      than half came to the Calgary area. Approximately 200,000 immigrants of various
      ethnic and cultural groups now live in the region. Many of these new arrivals
      have no natural support networks while struggling with language, cultural, and
      economic barriers. Recognizing these difficulties, the Calgary and Area Child and
      Family Services Authority (CFSA) joined with several Immigrant Serving Agencies
      to develop guidelines and procedures to direct staff working with diverse
      cultures, including the Call-Centre pilot project, which provided CFSA staff with
      a one-stop telephone contact for information about an immigrant or refugee
      family, their culture, and available culturally-appropriate resources. The Call
      Centre, which is currently being evaluated by researchers at the University of
      Calgary, will gradually expand to all CFSA sites in the region. This article
      describes the Call-Centre and the first phase of the evaluation.

PMID- 16435660
TI  - In the "best interest" of immigrant and refugee children: deliberating on their
      unique circumstances.
AB  - Each year, state juvenile courts provide thousands of immigrant and refugee
      children with access to consistent and reliable caregiving and a stable
      environment. To examine how courts interpret "the best interests" of immigrant
      and refugee children, this article examines 24 cases in courts across the United
      States, which indicate they use a territorial approach when evaluating the best
      interests standard. Although legal status was not an issue, many related factors
      were. Consequently, the courts restricted immigrant parents' rights in caring,
      guiding, and visiting their children; increased the risk of wrongfully
      terminating parental rights; and intensified the unpredictability of immigrant
      and refugee children's welfare in the long run. This article suggests an approach
      that encourages communication between social workers and the courts to address
      the special needs and circumstances of immigrant and refugee children on three
      key topics: the material and moral welfare of the child, and social welfare for
      immigrant and refugee families.

PMID- 16435661
TI  - An educational model for child welfare practice with English-speaking Caribbean
      families.
AB  - Implemented in New York City, the Child Welfare Fellowship Project is an
      international collaboration between social work educators in the United States
      and Jamaica, the West Indies, the public child welfare agency, and selected
      community-based agencies. This model educational program prepared selected
      Masters of Social Work (MSW) Fellowship students for exemplary child welfare
      practice with English-speaking Caribbean families by providing enhanced programs
      designed to support culturally competent skill development and a preventive
      approach to child welfare practice. These educational enhancements, combined with
      academic course work, increased professionalism, self-efficacy, and culturally
      competent skill development among participants and averted foster care placement
      for families seen over the duration of the project.

PMID- 16435662
TI  - Bridging refugee youth and children's services: a case study of cross-service
      training.
AB  - Bridging Refugee Youth and Children's Services(BRYCS), a public-private
      partnership between the federal Office of Refugee Resettlement, Lutheran
      Immigration and Refugee Service, and the United States Conference of Catholic
      Bishops, provides national technical assistance to public child welfare. After a
      series of "community conversations," BRYCS identified a lack of knowledge among
      child welfare staff about newcomer refugees, negative stereotypes, and a fear of
      child protective services among refugees. BRYCS initiated a number of technical
      assistance initiatives, including a pilot cross-service training project in St.
      Louis to strengthen collaboration between child welfare and refugee-serving
      agencies. This article details the lessons learned from this training and
      recommends changes in policy and practice.

PMID- 16435663
TI  - Pulling together.

PMID- 16435665
TI  - Technology. Protecting IT.

PMID- 16435664
TI  - Bed sores point to larger issue.

PMID- 16435666
TI  - Patient care. The safety network.

PMID- 16435667
TI  - Patient care. Wireless washings.

PMID- 16435668
TI  - Policy. Brailer Q&A.

PMID- 16435669
TI  - Fraud & abuse. Cyber sleuths.

PMID- 16435670
TI  - Technology. To Wi-Fi or not to.

PMID- 16435671
TI  - Quality. Improving surgery.

PMID- 16435672
TI  - Data page. The cost of hospital care.

PMID- 16435673
TI  - The new consumer, part 1.

PMID- 16435674
TI  - C-suite meltdown.
AB  - Personality dashes among senior managers can weaken leadership and wreak havoc on
      the entire hospital. What traits should raise red flags when hiring or promoting
      executives and how can conflicts be averted? The second part of our cover package
      looks at hospitals that nurture talent within their own ranks by creating
      leadership training programs.

PMID- 16435676
TI  - A rural crossroad.
AB  - The critical access hospital program is one of the few positive things for
      hospitals to come out of the 1997 Balanced Budget Act. It has meant salvation for
      the nearly 1,200 hospitals that have received the designation, and enables them
      to invest in facility upgrades, new equipment and additional staff. But a
      revamped Medicare managed care initiative threatens their payments and the
      Centers for Medicare & Medicaid Services and the Medicare Payment Advisory
      Program are taking a hard look at the program's costs. Some observers fear
      changes could be proposed that would weaken the CAH program.

PMID- 16435677
TI  - Building a consumer-directed service culture.
AB  - Consumers are expected to play a larger role in health care, a trend that will
      require employers, insurers, the government and providers to radically change
      assumptions and processes. Organizations that value consumer input, promote
      quality and choice, educate the public and provide services that people want at
      prices they are willing to pay may be said to have a consumer-directed service
      culture. What are the three building blocks to creating a consumer-directed
      service culture? How will technology and other breakthroughs continue to change
      and enrich that culture? And what is your role?

PMID- 16435678
TI  - Safer surgery.

PMID- 16435679
TI  - Taskmaster: managing yourself and others on scene.

PMID- 16435680
TI  - Stoopid medicine: are we doing stuff for people, or to them?

PMID- 16435681
TI  - Pass the ammunition. What went wrong in the gulf coast?

PMID- 16435682
TI  - Acadian ambulance got it done. Private ambulance company coordinates rescue
      efforts in New Orleans.

PMID- 16435683
TI  - Hurricane evacuations: the Georgia response.

PMID- 16435684
TI  - Fantastic finds. Top products from EMS EXPO 2005: part 2.

PMID- 16435685
TI  - EMS: it's about customer service.

PMID- 16435686
TI  - Prehospital management of the psychotic and aggressive patient with bipolar
      disease.

PMID- 16435687
TI  - Clean & clear on Khao Lak beach.

PMID- 16435688
TI  - National Conference prepares first receivers for mass casualty incidents.

PMID- 16435689
TI  - Visual difficulties reported by low-vision and nonimpaired older adult drivers.
AB  - Nonimpaired and low-vision older adults responded to a questionnaire regarding
      the types of visual difficulties experienced while performing daily tasks and
      while driving. Using the factors produced from a factor analysis as predictors, a
      discriminant analysis was performed to determine whether significant differences
      in visual problems existed between the groups. The majority of participants
      reported that they currently required more time than in the past to perform tasks
      that depended on their vision, regardless of their visual status. All
      participants reported experiencing significant difficulties with static and
      dynamic acuity, peripheral vision, illumination problems, and contrast
      sensitivity. Both nonimpaired and low-vision older adult drivers reported
      experiencing difficulty with glare, peripheral vision, and night driving. Low
      vision drivers reported experiencing unique difficulties with near acuity,
      distant acuity, and physical obstructions. Potential applications of this
      research include suggestions for redesigning automobiles and highway signs for
      safer use and viewing.

PMID- 16435690
TI  - Mission control of multiple unmanned aerial vehicles: a workload analysis.
AB  - With unmanned aerial vehicles (UAVs), 36 licensed pilots flew both single-UAV and
      dual-UAV simulated military missions. Pilots were required to navigate each UAV
      through a series of mission legs in one of the following three conditions: a
      baseline condition, an auditory autoalert condition, and an autopilot condition.
      Pilots were responsible for (a) mission completion, (b) target search, and (c)
      systems monitoring. Results revealed that both the autoalert and the autopilot
      automation improved overall performance by reducing task interference and
      alleviating workload. The autoalert system benefited performance both in the
      automated task and mission completion task, whereas the autopilot system
      benefited performance in the automated task, the mission completion task, and the
      target search task. Practical implications for the study include the suggestion
      that reliable automation can help alleviate task interference and reduce
      workload, thereby allowing pilots to better handle concurrent tasks during single
      and multiple-UAV flight control.

PMID- 16435691
TI  - Target acquisition with UAVs: vigilance displays and advanced cuing interfaces.
AB  - Vigilance and threat detection are critical human factors considerations in the
      control of unmanned aerial vehicles (UAVs). Utilizing a vigilance task in which
      threat detections (critical signals) led observers to perform a subsequent manual
      target acquisition task, this study provides information that might have
      important implications for both of these considerations in the design of future
      UAV systems. A sensory display format resulted in more threat detections, fewer
      false alarms, and faster target acquisition times and imposed a lighter workload
      than did a cognitive display format. Additionally, advanced visual, spatial
      audio, and haptic cuing interfaces enhanced acquisition performance over no cuing
      in the target acquisition phase of the task, and they did so to a similar degree.
      Thus, in terms of potential applications, this research suggests that a sensory
      format may be the best display format for threat detection by future UAV
      operators, that advanced cuing interfaces may prove useful in future UAV systems,
      and that these interfaces are functionally interchangeable.

PMID- 16435692
TI  - An attempt to evaluate mental workload using wavelet transform of EEG.
AB  - An attempt was made to evaluate mental workload using a wavelet transform of
      electroencephalographic (EEG) signals. Participants performed a continuous
      matching task at three levels of task difficulty. EEG signals during the task
      were recorded continuously from Fz, Cz, and Pz. The reaction time increased as
      the difficulty of the task increased. The percentage correct decreased as the
      task became more difficult. In accordance with this, the rating score on the NASA
      Task Load Index tended to increase with increased task difficulty. The EEG
      signals were analyzed using wavelet transform to investigate time-frequency
      characteristics. The total power at theta, alpha, and beta frequency bands and
      the time that the maximum power appeared for the three frequency bands were
      extracted from the scalogram. Increasing cognitive task difficulty seems to delay
      the time at which the central nervous system works most actively. These measures
      were found to be sensitive indicators of mental workload and could differentiate
      three cognitive task loads (low, moderate, and high) with high precision. Actual
      or potential applications of this research include a method that is relatively
      quick and accurate, compared with traditional methods, for the evaluation of
      mental workload.

PMID- 16435693
TI  - Heuristic automation for decluttering tactical displays.
AB  - Tactical displays can quickly become cluttered with large numbers of symbols that
      can compromise effective monitoring. Here, we studied how heuristic automation
      can aid users by intelligently "decluttering" the display. In a realistic
      simulated naval air defense task, 27 experienced U.S. Navy users monitored a
      cluttered airspace and executed defensive responses against significant threats.
      An algorithm continuously evaluated aircraft for their levels of threat and
      decluttered the less threatening ones by dimming their symbols. Users
      appropriately distrusted and spot-checked the automation's assessments, and
      decluttering had very little effect on which aircraft were judged as
      significantly threatening. Nonetheless, decluttering improved the timeliness of
      responses to threatening aircraft by 25% as compared with a baseline display with
      no decluttering; it was especially beneficial for threats in more peripheral
      locations, and 25 of 27 participants preferred decluttering. Heuristic
      automation, when properly designed to guide users' attention by decluttering less
      important objects, may prove valuable in many cluttered monitoring situations,
      including air traffic management, crisis team management, and tactical situation
      awareness in general.

PMID- 16435694
TI  - Assessing the effects of positive feedback and reinforcement in the introduction
      phase of an ergonomic intervention.
AB  - Resistance to change is common in ergonomic interventions, often resulting in
      negative consequences when the intervention's effectiveness is studied. A lab
      based study assessed the effects of positive reinforcement during the
      intervention process. On Day 1 all participants performed a simple screw-driving
      task that placed stress on the cervicobrachial region through static loading. On
      Day 2 a control group received basic information about ergonomics and then
      performed the task using an ergonomic intervention that has been shown to reduce
      loading on these muscle groups. The experimental group received the same basic
      information but also received positive reinforcement while performing the task
      with the ergonomic intervention. Subjective task assessment surveys and body-part
      discomfort surveys were administered, and these, along with speed of performance,
      were assessed in both groups. The results showed a significantly (p < .05) more
      positive subjective impression of the intervention for the feedback group than
      for the control group (29%-57% improvement) with no real changes in either the
      performance or discomfort levels. Applications of this research include improving
      workers' acceptance of ergonomic interventions in industrial and other settings.
      The reinforcement technique evaluated in this paper has yielded consistently
      positive effects in our ongoing ergonomic intervention research.

PMID- 16435696
TI  - A normative database of thumb circumduction in vivo: center of rotation and range
      of motion.
AB  - This article reports a systematic research effort aimed at establishing a
      normative database of thumb circumduction range of motion (ROM) and related
      kinematic characteristics in vivo while examining the effects of anthropometry,
      gender, and direction of rotation. Twenty-eight (14 men, 14 women)
      anthropometrically diverse participants performed maximum voluntary thumb
      circumductions as the trajectories of the surface markers placed on their thumb
      landmarks were recorded by an optoelectronic motion capture system. A
      globographic representation method was employed to model the measured marker
      trajectories, determining the center of rotation and central reference axes for
      thumb circumduction. Thumb ROM was quantified using (a) the joint sinuses
      expressing the thumb orientation change with respect to the reference axes and
      (b) cone volumes circumscribed by the thumb at the distal phalangeal,
      interphalangeal, and metacarpophalangeal levels. Data analyses resulted in
      statistical summaries of the derived kinematic and ROM measures with significant
      effects identified and regression equations predicting the cone volumes.
      Potential applications of this research include ergonomic design of hand-operated
      controls or devices and evaluation of thumb impairments or disorders.

PMID- 16435695
TI  - Low-back biomechanics and static stability during isometric pushing.
AB  - Pushing and pulling tasks are increasingly prevalent in industrial workplaces.
      Few studies have investigated low-back biomechanical risk factors associated with
      pushing, and we are aware of none that has quantified spinal stability during
      pushing exertions. Data recorded from 11 healthy participants performing
      isometric pushing exertions demonstrated that trunk posture, vector force
      direction of the applied load, and trunk moment were influenced (p < .01) by
      exertion level, elevation of the handle for the pushing task, and foot position.
      A biomechanical model was used to analyze the posture and hand force data
      gathered from the pushing exertions. Model results indicate that pushing
      exertions provide significantly (p < .01) less stability than lifting when
      antagonistic cocontraction is ignored. However, stability can be augmented by
      recruitment of muscle cocontraction. Results suggest that cocontraction may be
      recruited to compensate for the fact that equilibrium mechanics provide little
      intrinsic trunk stiffness and stability during pushing exertions. If one
      maintains stability by means of cocontraction, additional spinal load is thereby
      created, increasing the risk of overload injury. Thus it is important to consider
      muscle cocontraction when evaluating the biomechanics of pushing exertions.
      Potential applications of this research include improved assessment of
      biomechanical risk factors for the design of industrial pushing tasks.

PMID- 16435697
TI  - Audio and visual cues in a two-talker divided attention speech-monitoring task.
AB  - Although audiovisual (AV) cues are known to improve speech intelligibility in
      difficult listening environments, little is known about their role in divided
      attention tasks that require listeners to monitor multiple talkers at the same
      time. In this experiment, a call-sign-based multitalker listening test was used
      to evaluate performance in two-talker AV configurations that combined zero, one,
      or two channels of visual information (neither, one, or both talkers visible)
      with zero, one, or two channels of audio information (no audio, both talkers
      played from the same loudspeaker, and both talkers played through different,
      spatially separated loudspeakers). The results were analyzed to determine the
      relative performance levels that would occur with each AV configuration with
      target information that was equally likely to originate from either of the two
      talkers in the stimulus. The results indicate that spatial separation of the
      audio signals has the greatest impact on performance in multichannel AV speech
      displays and that caution should be used when presenting a visual representation
      of only a single talker unless that talker is known to be the highest priority
      talker in the combined AV stimulus. Potential applications of this research
      include the design of improved audiovisual speech displays for multichannel
      communications systems.

PMID- 16435698
TI  - Sharing control between humans and automation using haptic interface: primary and
      secondary task performance benefits.
AB  - This paper describes a paradigm for human/automation control sharing in which the
      automation acts through a motor coupled to a machine's manual control interface.
      The manual interface becomes a haptic display, continually informing the human
      about automation actions. While monitoring by feel, users may choose either to
      conform to the automation or override it and express their own control
      intentions. This paper's objective is to demonstrate that adding automation
      through haptic display can be used not only to improve performance on a primary
      task but also to reduce perceptual demands or free attention for a secondary
      task. Results are presented from three experiments in which 11 participants
      completed a lane-following task using a motorized steering wheel on a fixed-base
      driving simulator. The automation behaved like a copilot, assisting with lane
      following by applying torques to the steering wheel. Results indicate that haptic
      assist improves lane following by least 30%, p < .0001, while reducing visual
      demand by 29%, p < .0001, or improving reaction time in a secondary tone
      localization task by 18 ms, p = .0009. Potential applications of this research
      include the design of automation interfaces based on haptics that support
      human/automation control sharing better than traditional push-button automation
      interfaces.

PMID- 16435699
TI  - Speech-based interaction in multitask conditions: impact of prompt modality.
AB  - Speech-based interaction is often recognized as appropriate for hands-busy, eyes
      busy multitask situations. The objective of this study was to explore prompt
      guided speech-based interaction and the impact of prompt modality on overall
      performance in such situations. A dual-task paradigm was employed, with tracking
      as a primary task and speech-based data input as a secondary task. There were
      three tracking conditions: no tracking, basic, and difficult tracking. Two prompt
      modalities were used for the speech interaction: a dialogue with spoken prompts
      and a dialogue with visual prompts. Data entry duration was longer with the
      speech prompts than with the visual prompts, regardless of whether or not there
      was tracking or its level of difficulty. However, when tracking was difficult,
      data entry duration was similar for both spoken and visual prompts. Tracking
      performance was also affected by the prompt modality, with poorer performance
      obtained when the prompts were visual. The findings are discussed in terms of
      multiple resource theory and the possible implications for speech-based
      interactions in multitask situations. Actual or potential applications of this
      research include the design of speech-based dialogues for multitask situations
      such as driving and other hands-busy, eyes-busy situations.

PMID- 16435700
TI  - Relationships among display features, eye movement characteristics, and reaction
      time in visual search.
AB  - The relative contribution of number of fixations and fixation duration to
      reaction time in visual search was investigated. Ten participants (age 20-24
      years) took part in each of two experiments. In Experiment 1, the experimental
      factors were display type (icon and file name), organization (arrangements with
      and without grouping), and number of stimuli presented (4, 8, and 16). In
      Experiment 2, a search task for a target stimulus (three prespecified random
      letters) was conducted, and the experimental factor was the display's layout
      complexity. Multiple regression analysis was used to examine whether reaction
      time was explained by a mediational model in which reaction time is mediated by
      eye movements and display features are not directly related to reaction time. The
      mediational model was not supported, and the effects of display features on
      reaction time were not attributable solely to eye movements. The interaction
      between number of fixations and fixation duration was also explored as a function
      of display features. As the display feature changed and the task became more
      difficult, the contribution of the number of fixations to explain the variation
      in reaction time became dominant for both experiments. Potential applications
      include measurements of cognitive ability, eye muscle balance disorders, and
      binocular fusion ability.

PMID- 16435701
TI  - Audibility of train horns in passenger vehicles.
AB  - Studies of accident rates associated with train horn bans indicate that motorists
      rely on horns to warn them of approaching trains. However, researchers have not
      yet established the levels of horn sounds necessary for detection at railroad
      crossings. The purpose of this study was to obtain baseline measures of the
      auditory component of the motorist's detection task. Horn sounds recorded in
      three test vehicles were presented to 20 normal-hearing listeners in quiet and in
      four types of vehicle interior noise: engine idling, ventilation fan off; engine
      idling, fan on; vehicle moving at 30 miles/hr (mph), fan off; and vehicle moving
      at 30 mph, fan on. Thresholds of the horn sounds were determined by an adaptive
      procedure. Mean thresholds were lowest in quiet (1.8-4.4 dBA) and highest for the
      30-mph, fan-on condition (49.7-58.4 dBA). Mean horn thresholds for all 12 noise
      conditions were more than 10 dB below the overall level of the vehicle interior
      noise. Our data are compared with those of previous studies and their
      implications are discussed. Actual or potential applications of this research
      include the establishment of a lower limit of signal-to-noise ratios required for
      the detection of horn sounds at highway-rail crossings.

PMID- 16435702
TI  - Attentive navigation for viewpoint control in virtual environments.
AB  - Three-dimensional virtual environments and teleoperation activities depend on the
      ability to position an egocentric viewpoint at meaningful locations. Evidence
      from foundational research has led to the development of control strategies that
      generally adopt an all-or-nothing approach to guiding the viewer to useful
      vistas. This work examines attentive navigation, a technique for partially
      automating viewpoint control to promote a supportive yet unscripted exploration
      of a virtual environment. A collection of three experiments was designed to
      assess the effectiveness of attentive navigation versus commonly used free
      navigation techniques. Results show that this approach has promising consequences
      for improving object recognition, developing an understanding of the
      configuration of objects, and searching for target objects. Actual or potential
      applications of this research include improved interaction techniques for
      extracting information from visual representations, virtual environments, and
      teleoperation experiences.

PMID- 16435703
TI  - Limitations in drivers' ability to recognize pedestrians at night.
AB  - This study quantified drivers' ability to recognize pedestrians at night. Ten
      young and 10 older participants drove around a closed road circuit and responded
      when they first recognized a pedestrian. Four pedestrian clothing and two beam
      conditions were tested. Results demonstrate that driver age, clothing
      configuration, headlamp beam, and glare all significantly affect performance.
      Drivers recognized only 5% of pedestrians in the most challenging condition (low
      beams, black clothing, glare), whereas drivers recognized 100% of the pedestrians
      who wore retroreflective clothing configured to depict biological motion (no
      glare). In the absence of glare, mean recognition distances varied from 0.0 m
      (older drivers, low beam, black clothing) to 220 m (722 feet; younger drivers,
      high beam, retroreflective biomotion). These data provide new motivation to
      minimize interactions between vehicular and pedestrian traffic at night and
      suggest garment designs to maximize pedestrian conspicuity when these
      interactions are unavoidable.

PMID- 16435704
TI  - Team task analysis: identifying tasks and jobs that are team based.
AB  - This paper presents initial information on the development and validation of
      three team task analysis scales. These scales were designed to quantitatively
      assess the extent to which a group of tasks or a job is team based. During a 2
      week period, 52 male students working in 4-person teams were trained to perform a
      complex highly interdependent computer-simulated combat mission consisting of
      both individual- and team-based tasks. Our results indicated that the scales
      demonstrated high levels of interrater agreement. In addition, the scales
      differentiated between tasks that were predetermined to be individual versus team
      based. Finally, the results indicated that job-level ratings of team workflow
      were more strongly related to team performance than were aggregated task-level
      ratings of team-relatedness or team workflow. These results suggest that the
      scales presented here are an effective means of quantifying the extent to which
      tasks or jobs are team based. A research and practical implication of our
      findings is that the team task analysis scales could serve as criterion measures
      in the evaluation of team training interventions or predictors of team
      performance.

PMID- 16435705
TI  - Augmented, pulsating tactile feedback facilitates simulator training of clinical
      breast examinations.
AB  - Haptic training devices can facilitate tactile skill development by providing
      repeatable exposures to rare stimuli. Extant haptic training simulator research
      primarily emphasizes realistic stimuli representation; however, the experiments
      reported herein suggest that providing augmented feedback can improve training
      effectiveness, even when the feedback is not natural. A novel clinical breast
      examination training device uses inflated balloons embedded in silicone to
      simulate breast lumps. Oscillating the balloon water pressure makes the lumps
      pulsate. The pulsating lumps are easier to detect than the static lumps used in
      current simulators, and this manipulation seems to effectively introduce trainees
      to small, deep lumps that are initially difficult to perceive. A study of 48
      medical students indicates that training with the dynamic breast model increased
      the number of lumps detected, F(1, 47) = 9.34, p = .004, decreased the number of
      false positives, F(1, 47) = 5.78, p = .020, and improved intersimulator skill
      transfer, F(1, 47) = 26.56, p < .001. The results suggest that at least in this
      case, augmented, tactile feedback increases training effectiveness, despite the
      fact that the feedback does not attempt to mimic any physical phenomenon present
      in the natural stimulus. Applications of this research include training
      techniques and tools for improved detection of palpable cancers.

PMID- 16435706
TI  - [Proceedings from the Hepatology Congress, 20-21 May 2005, Potsdam, Germany].

PMID- 16435707
TI  - [Conventional laboratory diagnosis: what? when? how often? why?].

PMID- 16435708
TI  - [Diagnostic imaging of the liver: sonography/CT/MRI--clinical significance].

PMID- 16435709
TI  - [Diagnosis and therapy: autoimmune hepatitis, primary biliary cirrhosis and
      primary sclerosing cholangitis].

PMID- 16435710
TI  - [Clinical findings and therapy of classical hereditary haemochromatosis (type
      1)].

PMID- 16435711
TI  - [Wilson's disease].

PMID- 16435712
TI  - [Diagnosis and therapy in hepatology: hepatitis B and D].

PMID- 16435713
TI  - [Treatment of hepatitis C--update 2005].

PMID- 16435714
TI  - [HIV and hepatitis coinfection].

PMID- 16435715
TI  - [Therapeutic challenges in viral hepatitis patients].

PMID- 16435716
TI  - [Hepatocellular carcinoma].

PMID- 16435717
TI  - [Alcoholic liver diseases].

PMID- 16435718
TI  - [Nonalcoholic steatohepatitis].

PMID- 16435719
TI  - [Drug-induced and toxic liver diseases].

PMID- 16435720
TI  - [Perspectives in hepatology in the next 2-3 years: what will be clinically
      relevant? Viral hepatitis].

PMID- 16435721
TI  - [Health economics in hepatology: who should pay? Is expensive treatment in
      hepatology cost effective?].

PMID- 16435722
TI  - [Acute liver failure--diagnosis and management].

PMID- 16435723
TI  - [Liver dialysis].

PMID- 16435724
TI  - [Ascites, spontaneous bacterial peritonitis and hepatorenal syndrome].

PMID- 16435725
TI  - [Portal hypertension and gastrointestinal bleeding].

PMID- 16435726
TI  - [Hepatic encephalopathy and hepatopulmonary syndrome].

PMID- 16435727
TI  - [Indication and exclusion criteria for living related liver transplantation].

PMID- 16435729
TI  - [Sports and physical exercise in liver disease].

PMID- 16435728
TI  - [Transplantation and liver resection for hepatocellular carcinoma in cirrhosis].

PMID- 16435730
TI  - [Perspectives in hepatology within the next 2-3 years: what becomes clinically
      relevant? Non-viral liver diseases].

PMID- 16435731
TI  - Contemporary views on female pelvic anatomy.

PMID- 16435732
TI  - Vaginal vault prolapse: identification and surgical options.
AB  - Reconstructive surgeons should be familiar with the identification and treatment
      of vaginal vault prolapse. Most utilized techniques can be effective in terms of
      suspension of the vaginal apex. New technology has allowed for the performance of
      vaginal-approach techniques with increasingly physiologic anatomic and functional
      outcomes (Figure 8).

PMID- 16435733
TI  - Anterior vaginal wall prolapse: innovative surgical approaches.

PMID- 16435734
TI  - Optimizing pelvic surgery outcomes.
AB  - Most perioperative complications related to graft use can be prevented by
      appropriate preoperative and postoperative tissue management. Intraoperative
      cystoscopy should be a routine part of most pelvic reconstructive procedures. A
      rectal examination should be performed at the end of each surgical procedure to
      document rectal integrity. Under most circumstances, graft erosions can be
      managed without the need to remove the entire graft or jeopardizing the surgical
      repair.

PMID- 16435735
TI  - Integrated water management for eutrophication control: public participation,
      pricing policy, and catchment modeling.

PMID- 16435736
TI  - Designing a multipurpose methodology for strategic environmental research: the
      Ronnea Catchment Dialogues.
AB  - The Ronnea Catchment Dialogues were developed as a multipurpose methodology to
      enable stakeholder-oriented, interdisciplinary research. This article describes
      the background of the Catchment Dialogues and their multiple aims and evaluates
      the Dialogue design. The three parallel objectives that were expected from the
      Catchment Dialogues were that they would function as a method to i) collect
      qualitative research data, ii) promote the involvement of stakeholders in water
      management, and iii) offer a practical example to enable integration of
      disciplines. Drawing on experiences from similar research or stakeholder
      involvement projects using focus groups and similar techniques, this article
      assesses how the research aim was fulfilled and how the balance between
      fulfilling different objectives was struck. It reflects on Catchment Dialogues as
      a fruitful research method for answering our research questions, specifically
      focusing on the "new" design features, i.e. heterogeneous groups, structured
      interviews (long hours), and external moderation. Conclusions show that Catchment
      Dialogues was a useful approach for achieving VASTRA's multiple purposes.

PMID- 16435737
TI  - Public participation in water resources management: stakeholder voices on degree,
      scale, potential, and methods in future water management.
AB  - The European Water Framework Directive puts strong emphasis on stakeholder and
      public participation in water management. Several practical questions regarding
      who should be involved, why, when, and how still remain unanswered. This paper
      investigates stakeholders' own experiences and views of increased public
      participation in water management. The article also explores the potential for
      increasing levels of participation by forming catchment committees with
      representation from stakeholder groups and through the use of various practical
      methods for participation. For both these aspects of participation, the views,
      expectations, and apprehensions of different stakeholder groups involved in
      nutrient loss management are investigated. Stakeholder opinions were collected by
      inviting representatives from five stakeholder groups within the Ronnea catchment
      in southern Sweden to a catchment dialog process.

PMID- 16435738
TI  - The Water Framework Directive: stakeholder preferences and catchment management
      strategies--are they reconcilable?
AB  - The key objective of the European Water Framework Directive (WFD) is to promote
      sustainable water use by protecting water resources. Here, we investigate how the
      economic consequences of a set of water management regulations is received by a
      group of stakeholders in the Ronnea catchment. We explore three themes from an
      economic point of view: i) perceived causes of eutrophication, ii) preferences
      regarding water use, and iii) the extent to which the polluter-pays principle
      should be applied. There is a common understanding about the intentions in the
      WFD to enhance cost-effective water use. All stakeholder groups largely share a
      similar picture of the causes of water quality deterioration. However, there is
      not one cost-effective and fair solution. Several mixes of remedial measures
      within the same catchment are possible, depending on the scale of action. Despite
      potential economic gains from cooperation between sectors, the participants
      regard the individual polluter-pays principle as the most feasible mode of
      funding for remedial programs, supported by subsidies. There is little demand for
      more market institutions (emission fees, tradable emission permits). The
      stakeholders have a conservative view of water management, i.e. they accept the
      present combination of regulations and economic incentives, and they are fully
      aware of the complexity of the issue. In general, the WFD recommendations for the
      calculation of cost-effective abatement strategies seem to imply an
      underestimation of the value of external effects in the decision-making process.

PMID- 16435739
TI  - Local stakeholders' acceptance of model-generated data used as a communication
      tool in water management: The Ronnea Study.
AB  - The objective of this study was to increase the knowledge of local stakeholders'
      acceptance of model-generated data when used as a communication tool in water
      quality management. The Ronnea catchment in the southwest of Sweden was chosen as
      the study area. The results indicate the model-generated data served as a uniting
      factor. Simultaneously, the stakeholders were concerned with presented data, the
      main problems being sources of pollution, which were not accounted for, lack of
      trustworthiness when measuring pollution, and the uncertainty of the impact of
      natural variation and delayed effects. Four clusters of factors were identified
      as influencing stakeholders' acceptance of the model-generated data: confidence
      in its practical applications, confidence in the people involved in or providing
      material for the dialog (such as experts, decision-makers, and media), the social
      characteristics of the participants (such as age and profession), and the way of
      communicating the data (such as tone of communication, group composition,
      duration, and geographical scope of the dialog). The perception of the fairness
      of the practical application of given model-generated data was also an important
      factor for acceptance.

PMID- 16435740
TI  - Integrated catchment modeling for nutrient reduction: scenarios showing impacts,
      potential, and cost of measures.
AB  - A hydrological-based model (HBV-NP) was applied to a catchment (1900 km2) in the
      southern part of Sweden. Careful characterization of the present load situation
      and the potential for improved treatment or reduced soil leaching were analyzed.
      Several scenarios were modeled to find strategies to reach the Swedish
      environmental goals of reducing anthropogenic nitrogen load by 30% and phosphorus
      load by 20%. It was stated that the goals could be reached by different
      approaches that would affect different polluters and social sectors. However, no
      single measure was enough by itself. Instead, a combination of measures was
      necessary to achieve the goals. The nitrogen goal was the most difficult to
      attain. In order to be cost-effective, these measures should be applied to areas
      contributing the most to the net loading of the sea. This strategy could reduce
      the costs by 70%-80% when compared with implementing the measures in the entire
      catchment. Integrated catchment models may thus be helpful tools for reducing
      costs in environmental control programs.

PMID- 16435741
TI  - Estimating catchment nutrient flow with the HBV-NP model: sensitivity to input
      data.
AB  - The dynamic catchment model HBV-N has been further developed by adding routines
      for phosphorus transport and is now called the HBV-NP model. The model was shown
      to satisfactorily simulate nutrient dynamics in the Ronnea catchment (1,900 km2).
      Its sensitivity to input data was tested, and results demonstrated the increased
      sensitivity to the selection of input data on a subcatchment scale when compared
      with the catchment scale. Selection of soil and land use databases was found to
      be critical in some subcatchments but did not have a significant impact on a
      catchment scale. Although acceptable on a catchment scale, using templates and
      generalization, with regards to emissions from point sources and rural
      households, significantly decreased model performance in certain subcatchments
      when compared with using more detailed local information. A division into 64
      subcatchments resulted in similar model performance at the catchment outlet when
      compared with a lumped approach. Adjusting the imported matrixes of the regional
      leaching of nitrogen, from agricultural land, against mean subcatchment water
      percolation did not have a significant impact on the model performance.

PMID- 16435742
TI  - Parameter precision in the HBV-NP model and impacts on nitrogen scenario
      simulations in the Ronnea river, southern Sweden.
AB  - The HBV-NP model is a newly developed water quality model that describes the
      turnover and fluxes of both nitrogen and phosphorous. It is based on the
      conceptual precipitation/runoff HBV model. The HBV-NP model was applied for
      simulation of nitrogen for the Ronnea catchment in southern Sweden. The catchment
      was divided into 64 subcatchments in the model. Discharge measurements from six
      stations and nitrogen measurements from 12 stations were used in the calibration
      of parameters in the model. Eight automatic calibrations were performed with
      different combinations of time periods, objective functions, and levels of the
      nitrogen load in the model. A regionally extended interpretation of the Nash
      Sutcliffe R2 criterion was used in the calibration. In the evaluation of the
      criterion, the errors were summed over both time steps and sampling points.
      Scenario simulations of combined measures for reduction of nitrogen load into the
      sea by 30% were thereafter performed with the eight sets of parameters
      established by calibration. The model parameters were not uniquely defined by the
      calibration. However, the simulated relative reduction of nitrogen load into the
      sea was relatively insensitive to the choice of parameter set, given the
      available input sources, variables, and data.

PMID- 16435743
TI  - Estimating reduction of nitrogen leaching from arable land and the related costs.
AB  - The EU Water Framework Directive will require river-basin management plans in
      order to achieve good ecological status and find the most cost-efficient nitrogen
      (N) leaching abatement measures. Detailed scenario calculations based on modeling
      methods will be valuable in this regard. This paper describes the approach and an
      application with a coefficient method based on the simulation model SOILNDB for
      quantification of N leaching from arable land and for prediction of the effect of
      abatement scenarios for the Ronnea catchment (1900 km2) in southern Sweden. Cost
      calculations for the different measures were also performed. The results indicate
      that the individual measures-cover crop and spring plowing, late termination of
      ley and fallow, and spring application of manure-would only reduce N leaching by
      between 5% and 8%. If all measures were combined and winter crops replaced by
      their corresponding spring variants, a 21% reduction in N leaching would be
      possible. However, this would require total fulfillment of the suggested
      measures.

PMID- 16435744
TI  - Modeling the impact of potential wetlands on phosphorus retention in a Swedish
      catchment.
AB  - In southern Sweden, wetlands are constructed to remove nitrogen (N) in
      agricultural catchments. The possible effects of such wetlands on riverine
      phosphorus (P) were also estimated using input-output data from three well
      monitored wetlands. This was done to formulate a simple model for removal of P
      that is dependent on inflow characteristics. Next, the N- and P-reducing effects
      of wetlands were modeled on a catchment scale (1900 km2) using the HBV-NP model
      and various assumptions about the wetland area and location. All three wetlands
      functioned as sinks for total P (tot-P) and for total suspended solids (TSS) with
      a removal of 10% to 31% and 28% to 50%, respectively. Mean P-removal rates of 17
      49 kg ha(-1) yr(-1) were well simulated with the model. Catchment scale
      simulations indicated that wetlands were more efficient (in percentage of load)
      as traps for P than for N and that this may motivate the construction of wetlands
      for P removal far upstream from the catchment outlet.

PMID- 16435745
TI  - Modeling the response of eutrophication control measures in a Swedish lake.
AB  - The response of a biogeochemical lake model (BIOLA) to different eutrophication
      management actions has been studied in a eutrophic lake. Management actions
      included in the study were nutrient load reduction, sediment manipulation,
      biomanipulation, and herbicide application. The model was used to simulate
      nutrient and biomass concentrations in the lake during the 1990s. During the same
      period, management scenarios were also simulated. Several ecological parameters
      were calibrated to better simulate the behavior of the chosen lake, but there
      were still some difficulties with phosphate. This indicated that further model
      development is necessary. The most favorable development within the lake was
      found for scenarios with nutrient load reduction and biomanipulation through
      planktivorous fish reduction. Reducing both the nitrogen and phosphorus loads had
      a greater effect on the lake's water quality than simply reducing just one of the
      nutrients.

PMID- 16435746
TI  - Climate change impact on water quality: model results from southern Sweden.
AB  - Starting from six regional climate change scenarios, nitrogen leaching from
      arable-soil, water discharge, and nitrogen retention was modeled in the Ronnea
      catchment. Additionally, biological response was modeled in the eutrophic Lake
      Ringsjon. The results are compared with similar studies on other catchments. All
      scenarios gave similar impact on water quality but varied in quantities. However,
      one scenario resulted in a different transport pattern due to less-pronounced
      seasonal variations in the hydrology. On average, the study shows that, in a
      future climate, we might expect: i) increased concentrations of nitrogen in the
      arable root zone (+50%) and in the river (+13%); ii) increased annual load of
      nitrogen from land to sea (+22%) due to more pronounced winter high flow;
      moreover, remote areas in the catchment may start to contribute to the outlet
      load; iii) radical changes in lake biochemistry with increased concentrations of
      total phosphorus (+50%), total nitrogen (+20%), and planktonic algae such as
      cyanobacteria (+80%).

PMID- 16435747
TI  - Social-ecological resilience and social conflict: institutions and strategic
      adaptation in Swedish water management.
AB  - Dealing with uncertainty and complexity in social-ecological systems is
      profoundly dependent on the ability of natural resource users to learn and adapt
      from ecological surprises and crises. This paper analyzes why and how learning
      processes are affected by strategic behavior among natural resource users and how
      social conflict is affected by social and ecological uncertainty. The claim is
      that social conflict among natural resource users seriously inhibits the
      possibilities of learning and adaptation in social-ecological systems. This is
      done combining insights from political science, experimental economics, and
      social-psychology and an analytical case study elaborating social conflict and
      institutional change in Swedish water management institutions. This paper also
      discusses the crucial role the institutional context plays in defining the
      outcome of learning processes in Swedish water management institutions and hence
      highlights previously poorly elaborated political aspects of learning processes
      and institutional change in social-ecological systems.

PMID- 16435748
TI  - Phase-in of nonpoint sources in a transferable discharge permit system for water
      quality management: setting permit prices.
AB  - The composite market design is a proposal for a transferable discharge permit
      system that specifically includes agricultural non-point-source dischargers and
      addresses both property rights and transaction cost problems. The first step to
      implementation of a composite market scheme is the estimation of a supply curve
      for abatement measures in the catchment area. Estimation is performed by
      combining costs with modeled loss reductions from selected best management
      practices and then using this information to estimate the supply curve for
      abatement, which in turn can then be used to set permit prices. The Ronnea
      catchment in southern Sweden is used as a pilot study area for making this type
      of estimate. Costs for existing measures that reduce nutrient losses from
      farmland (catch crops and spring planting) are based on existing programs
      financed by the Swedish Agricultural Board. A set of supply curves is calculated
      for these measures using retention estimates for seven subcatchments and three
      soil types in the area. Although existing information is sufficient to calculate
      partial supply curves and may be used to set permit prices, additional measures
      should be included as well as an increased number of variables for
      differentiating site specific reduction costs.

PMID- 16435749
TI  - CATCH: a method for structured discussions and a tool for decision support.

PMID- 16435750
TI  - Positive and negative consequences of a military deployment.
AB  - This study determined the perception by 951 U.S. Army soldiers of positive and
      negative consequences of a peacekeeping deployment to Bosnia. Seventy-seven
      percent reported some positive consequences, 63% reported a negative consequence,
      and 47% reported both. Written comments were also provided. Of the 951 soldiers,
      478 wrote at least one positive comment and 403 at least one negative comment.
      Single soldiers were more likely than married soldiers to report positive
      consequences (82% vs. 72%). Married soldiers were more likely than single
      soldiers to report negative consequences (70% vs. 55%). Positive consequences
      included making additional money, self-improvement, and time to think. Negative
      consequences included the military chain of command, being away from home, and
      deterioration of marital/significant other relationships.

PMID- 16435751
TI  - Rank in Self-Defense Forces and risk factors for atherosclerotic disease.
AB  - Socioeconomic status is associated with prevalence of and risk for
      atherosclerotic disease. We investigated the relationship between rank in the
      Self-Defense Forces (SDFs) and risk factors for atherosclerotic disease among
      middle-aged, male, SDFs personnel. Subjects were classified into five groups
      according to their ranks in the SDFs, i.e., class 1 (lowest, n = 289), class 2
      (low, n = 170), class 3 (middle, n = 229), class 4 (high, n = 197), and class 5
      (highest, n = 89). Low rank was associated with current cigarette smoking,
      alcohol abstaining, and poorer vegetable consumption. It was also associated with
      prevalence of type 2 diabetes, elevated gamma-glutamyltransferase activity, and
      high white blood cell counts. Prevalence of obesity, hypertension,
      hypercholesterolemia, hypertriglyceridemia, or hyperuricemia was not associated
      with rank in this population. Rank may be regarded as one of the markers that
      reflect individual health states among middle-aged male personnel.

PMID- 16435752
TI  - How shall we train?
AB  - The prosecution of modern war and the competing missions of peacekeeping,
      humanitarian missions, and beneficiary care place great demands on the military
      medical system. Meeting the military medical training challenges of the new
      millennium requires the best trained and most experienced medical personnel
      possible. Various strategies for initial and sustainment (continuing) medical
      training are available to ensure that the medical force is ready for the next
      mission. Accredited programs both in and out of the military are the mainstay of
      training for both enlisted personnel and officers, with professional
      certification serving as the standard for competency. Clinical sustainment
      training can take place in military medical treatment facilities, civilian
      institutions, or a combination of the two. When direct patient care opportunities
      cannot provide the proper mixture of experiences to maintain certain skills,
      short courses, distance education, and patient simulators can play important
      roles. Because each training strategy offers certain advantages in different
      settings, it is likely that military medical departments will need to use all of
      them. An optimal training environment benefits from all strategies used, in
      combination or separately.

PMID- 16435753
TI  - Field-user acceptability of new camouflage face paint formulations in the
      Republic of Korea.
AB  - New formulations of camouflage face paint (CFP), one with 30% N,N-diethyl-3
      methylbenzamide (DEET) and the other without DEET, were evaluated for soldier
      user acceptability during a military field-training exercise in the Republic of
      Korea. Soldiers testing the CFP formulations were members of one of four U.S.
      Army infantry companies (A, B, C, or D). The formulations were evaluated while
      soldiers participated in simulated combat exercises for 5 days during hot, humid
      summer weather in Korea. Results showed that soldiers found both of the new
      formulations easier to apply (91.3% of respondents who used CFP without DEET and
      87.9% of respondents who used CFP with DEET) and remove (82.6% without DEET and
      81.2% with DEET) than the previous standard military-issue CFP. Soldier
      acceptability was higher for the new CFP formulation with 30% DEET (70.5%) than
      for the formulation without 30% DEET (52.9%). Soldiers recommended it more
      frequently (70.5%) than the formulation without 30% DEET (50.0%). The new CFP
      formulation with 30% DEET was rated more often (79.5%) as either good or
      excellent than the new formulation without 30% DEET (67.4%). Soldiers reported
      that the CFP formulation with 30% DEET more successfully camouflaged the face
      (92.7%) than the formulation without 30% DEET (80.0%).

PMID- 16435754
TI  - Linkage between the Israeli Defense Forces primary care physician demographics
      and usage of secondary medical services and laboratory tests.
AB  - BACKGROUND: The primary care physicians in the Israeli Defense Forces, as in the
      Israeli civilian health system, have two major subpopulations. Graduates of
      Israeli schools of medicine, and graduates of foreign medical schools, most of
      them in Eastern Europe. OBJECTIVE: To evaluate differences in the referral
      patterns of primary care physicians according to their graduation institution and
      demographic characteristics. METHODS: The study took place in one primary care
      practice in central Israel. The referrals to consultations and laboratory tests
      over a period of 1 year were evaluated. Physicians that had less than 37
      encounters were excluded from the study. Data were extracted from the central
      computerized databases of the Medical Corps and Israeli Defense Forces. RESULTS:
      Sixty-eight physicians had a total of 18,402 encounters that resulted in 23,845
      outcomes. There were no associations between demographic and training backgrounds
      of the physicians and their actual referral rates to consultations and laboratory
      tests. CONCLUSION: The background data of the primary care physicians does not
      predict their referral patterns and their role as "gate keepers".

PMID- 16435755
TI  - Senior military officers' educational concerns, motivators and barriers for
      healthful eating and regular exercise.
AB  - The increasing trend of overweight in the military, the high cost of health care
      associated with overweight, and the failure to meet some Healthy People 2000
      objectives related to diet identify the need for more appropriate nutrition and
      fitness education for military personnel. The purpose of this study was to assess
      senior military officers' concerns on various health topics, educational
      preferences for nutrition and health topics, eating habits, and barriers and
      motivators for eating healthfully and exercising regularly. The survey was
      completed by 52 resident students at the U.S. Army War College. Fitness, weight,
      and blood cholesterol were top health concerns, and respondents wanted to know
      more about eating healthfully on the run. The primary barrier to eating
      healthfully and exercising regularly was lack of time, whereas health and
      appearance were top motivators. Health interventions for this population should
      include their topics of concern and should address perceived barriers and
      motivators.

PMID- 16435756
TI  - The impact of National Guard activation for homeland defense: employers'
      perspective.
AB  - Data gathered from a study of reserve component (RC) soldiers who were activated
      during the spring of 2002, following the terrorist attacks of September 11, 2001,
      suggested that they were concerned about how the effects of their activation
      affected their civilian employment. Therefore, the purpose of this study was to
      obtain this information from the civilian employers of these RC soldiers. Most
      civilian employers who participated in this study (N = 28) were male (89%) and
      working in law enforcement (39%). Fifty-six percent of employers gave consent to
      be interviewed by telephone. Although supervisors reported difficulties in
      several areas of operation and aspects of the RC activation, they still supported
      the activation of their RC employees and their military mission. This study is a
      significant start to illuminating the important roles that both RC employees and
      their civilian employers play in homeland defense.

PMID- 16435757
TI  - Navy physical readiness test scores and body mass index (Spring 2002 cycle).
AB  - Physical performance and risk factors from the U.S. Navy physical readiness test
      (PRT) were analyzed in a retrospective, cross-sectional, population-based study
      using data from the Spring 2002 cycle. PRT scores were available for 22,314
      active duty women and 131,287 men, and risk factor information was available for
      4,254 women and 31,503 men. For risk factors, self-reported smoking rates were
      higher for men than women, and decreased with increasing age. Self-reported rates
      for elevated cholesterol and joint problems increased with increasing age. Linear
      regression showed body mass index increased with age for men (constant = 25.6,
      increasing 0.0,765 per year of age over 18 years, p = 0.000) and were increasing
      at a lower rate for women (constant = 24.5 increasing 0.0,159 per year of age
      over 18 years, p = 0.000). Increasing body mass index was associated with
      decreasing PRT performance. This analysis provides population-based information
      on the PRT risk factors, body mass index, and physical fitness for Navy
      personnel.

PMID- 16435758
TI  - The Balanced Scorecard versus Total Quality Management: which is better for your
      organization?
AB  - Today's health care organizations must deal with managed care, government
      oversight, aging baby boomers, new technologies, and increasing pharmaceutical
      prices. It is imperative that health care organizations adopt some form of
      business strategy to manage the vast amount of information available. Two of the
      more popular strategies among health care organizations are the Balanced
      Scorecard and Total Quality Management. Which one of the strategies is best for
      an organization? The answer to this question is that it depends on the
      organization. This article provides the fundamentals of each strategy and
      contrasts their strengths and weaknesses, so that interested organizations can
      make informed decisions regarding the best strategy for each organization.

PMID- 16435759
TI  - Iranian military forces in the Bam earthquake.
AB  - The earthquake that struck Bam, Iran, in December 2003 was one of the most
      catastrophic natural disasters in recent years. Medical and assistance activities
      conducted by Iranian military forces in this event are discussed in light of the
      special capabilities of the military forces in search and rescue missions. Among
      the most significant activities of the Iranian military forces in this event are
      the following: reporting the first news about the event, starting search and
      rescue missions in the first hour after the disaster by the 1st Brigade of Bam as
      the first assisting force, setting up two field hospitals as the first Iranian
      field hospitals in the disaster area, transporting 937 assistance, medical, and
      health care personnel to the disaster area in the first day, setting up 23 field
      emergency and 13 field assistance centers in the area, running 8 post-hospital
      care centers throughout the country, and playing a significant role in airlifting
      11,792 casualties to different hospitals around the country. Based on the recent
      experience and the exclusive abilities of military forces, a special role for
      these forces in search and rescue missions should be considered.

PMID- 16435760
TI  - Assessment of trauma exposure and post-traumatic stress in long-term care
      veterans: preliminary data on psychometrics and post-traumatic stress disorder
      prevalence.
AB  - This article reports preliminary data on trauma and post-traumatic stress
      disorder (PTSD) prevalence, as well as test psychometrics, among 35 cognitively
      intact veterans residing in long-term care settings. Participants received a
      traumatic event screening, the Mini-Mental Status Examination, Combat Exposure
      Scale (CES), PTSD Checklist (PCL), and Mississippi Combat PTSD Scale (M-PTSD).
      Results demonstrated adequate reliability for the CES, PCL, and M-PTSD for use in
      these settings, with several significant intercorrelations. A high prevalence of
      trauma exposure was found, in particular combat. Based on the PCL and M-PTSD,
      although most veterans did not meet full PTSD diagnostic criteria, a moderate
      proportion met partial criteria. The need for assessment and treatment of trauma
      exposure and PTSD in Veterans Affairs long-term care settings is emphasized.

PMID- 16435761
TI  - Post-traumatic stress disorder claims from the viewpoint of veterans service
      officers.
AB  - OBJECTIVE: To situate veterans' experience of the Department of Veterans Affairs
      claims process in a broader context, this study explored the beliefs of veterans
      service officers (VSOs) about the Department of Veterans Affairs disability
      claims process for post-traumatic stress disorder (PTSD). METHODS: A mail survey
      of the county and national VSOs working in Minnesota was performed.
      Questionnaires included a modified version of the Disability Application
      Appraisal Inventory. RESULTS: Most VSOs believe thatveterans value the Department
      of Veterans Affairs disability status for PTSD to obtain validation for what they
      experienced in the military and that veterans have negative reactions to the
      claims process for PTSD. VSOs' satisfaction with the claims process was
      associated with beliefs about its fairness. CONCLUSIONS: In general, VSOs'
      beliefs about the reasons veterans value service connection for PTSD parallel
      those veterans report. More work is needed to determine how VSOs influence
      veterans, to determine whether PTSD claimants have special or unique needs as
      they undergo the claims process, and to explore fairness concerns.

PMID- 16435762
TI  - Fluid consumption and the potential role of canteen shape in minimizing
      dehydration.
AB  - Hypohydration can unknowingly occur in military personnel during exertion,
      especially in the heat. Such dehydration can impair cognitive and physical
      performance. Some portion of exercise-induced dehydration may be offset by
      changing the perceptual biases of soldiers when filling and drinking from
      canteens. Using comparably sized water bottles, we investigated this perceptual
      bias with 50 Army and Marine ROTC students by showing that those given short,
      wide, clear water bottles poured and drank more water than those given taller
      bottles that held the same volume. Even although those given short, wide water
      bottles poured 38% more water, they did not perceive themselves as having poured
      or drunk more. The implications for decreasing dehydration in the field and in
      garrison are discussed.

PMID- 16435763
TI  - The cigarette manufacturers' efforts to promote tobacco to the U.S. military.
AB  - This article describes findings from review of tobacco industry documents
      regarding promotion of tobacco to the military, and efforts to influence
      Department of Defense policies regarding the use and sale of tobacco products.
      The documents reveal that the industry has targeted the military for decades for
      reasons including: (1) the volume of worldwide military personnel; (2) the
      opportunity to attract young men who fit a specific socioeconomic and cultural
      profile; (3) potential carryover of profits to civilian markets; and (4) the
      unusual price structure of commissaries and exchanges. The industry used
      distinctive promotion methods such as in-store merchandising, sponsorships, and
      even brand development to target the military, both in the United States and
      abroad during times of conflict. Legislative activity to protect tobacco
      promotion to this vulnerable population was carried out in response to smoking
      policy changes proposed by the Department of Defense. The tobacco industry has
      contributed to the high prevalence of smoking in the military and among veterans.

PMID- 16435764
TI  - Carlos Finlay and yellow fever: triumph over adversity.
AB  - The eradication of yellow fever in Havana, Cuba, was achieved by a fruitful
      collaboration between American and Cuban physicians. Carlos Finlay, a Cuban
      physician who proposed the mosquito-vector theory in 1881, shared his ideas, his
      publications, and a sample of mosquito eggs with the U.S. Army Yellow Fever
      Commission. The commission, headed by MAJ Walter Reed, used human volunteers to
      confirm Finlay's theory. MAJ William Gorgas adopted mosquito-control measures in
      his sanitation program and, within 6 months, yellow fever was controlled in
      Havana for the first time. Finlay held fast to his ideas despite incredulity and
      ridicule. His tenacity and scientific honesty vindicated his ideas about yellow
      fever.

PMID- 16435765
TI  - Protecting our militaries: a systematic literature review of military human
      immunodeficiency virus/acquired immunodeficiency syndrome prevention programs
      worldwide.
AB  - OBJECTIVES: To systematically review published studies of human immunodeficiency
      virus (HIV)/acquired immunodeficiency syndrome (AIDS) prevention programs
      targeting the world's military populations. METHODS: We systematically searched
      eight electronic databases (publications from 1983 to February 2005) and hand
      searched the bibliographies of HIV/AIDS prevention reviews to identify evaluative
      studies of HIV/AIDS prevention interventions for military personnel. RESULTS:
      Five hundred eighty-four abstracts were identified, of which eight met formal
      acceptance criteria. Four prevention interventions were identified, with each
      reporting a positive intervention effect on one or more of the following
      outcomes: increasing soldiers' knowledge of HIV/AIDS, willingness to engage in
      preventive behaviors, changing their attitudes toward greater compliance with
      prevention guidelines, and HIV/AIDS incidence and prevalence. CONCLUSIONS:
      Published interventions to reduce the risk of HIV/AIDS among military personnel
      are effective under certain conditions and with a limited number of populations.
      We discuss problems inherent in such research and make recommendations to improve
      the development, evaluation, and dissemination of findings of comprehensive
      HIV/AIDS prevention programs among military populations.

PMID- 16435766
TI  - Condom use by male, enlisted, deployed navy personnel with multiple partners.
AB  - STUDY QUESTION: Condom use by male enlisted personnel deployed on an aircraft
      carrier in spring 2002 who reported having casual sex partners in foreign ports
      and (1) only a steady partner, (2) only casual sex partners, or (3) both steady
      and casual sex partners in the home port. STUDY DESIGN: Cross-sectional survey,
      with analysis of the subsample reporting multiple partners (n = 378). RESULTS:
      Sexual behavior was less frequent and condom use was higher in foreign ports (p <
      0.0001). Men involved with both steady and casual partners used condoms less
      consistently than did those involved with only casual partners (p < 0.05). Sexual
      behavior also varied with the type of partner (p < 0.0001). CONCLUSIONS: Navy
      strategies promoting condom use in foreign ports appear effective. New strategies
      are needed for home ports and for men involved with both steady and casual
      partners.

PMID- 16435768
TI  - Music to our ears.

PMID- 16435767
TI  - DNA mutations in animals.

PMID- 16435769
TI  - Congrats to HH authors.

PMID- 16435770
TI  - Beg to differ.

PMID- 16435771
TI  - Because of Winn-Dixie.

PMID- 16435772
TI  - Identify and capitalize on your lab's molecular potential.

PMID- 16435773
TI  - Serum tumor markers. Part I: Clinical utility.
AB  - Most tumor markers in current use are glycoproteins that are measured by routine
      immunoassay techniques. The primary utility of serum tumor markers is for
      evaluating the effectiveness of therapy in advanced stages of cancer; in
      addition, they are used for monitoring "cured" patients for cancer recurrence.
      Regrettably, this latter use has not led to a significant improvement in patient
      outcomes when a recurrence is detected early. Sensitivity and/or specificity is
      frequently lacking for most tumor marker tests and their utility as screening
      tools to detect early cancer is extremely limited. For the most part, decisions
      based on the concentration of these cancer-associated molecules should always be
      made in light of the entire clinical picture. A monumental goal in cancer
      research is to find markers that are significantly more sensitive and specific
      for early cancer detection, as well as the other uses described herein. In Part
      II of this series, practical considerations and limitations regarding laboratory
      testing of tumor markers will be addressed.

PMID- 16435775
TI  - An accessible, multipronged approach advances lab business education.

PMID- 16435774
TI  - A lab's strategy to reduce errors depends on automation.

PMID- 16435776
TI  - Addressing management issues.

PMID- 16435777
TI  - Could new lab-report policy open a "Pandora's box"?

PMID- 16435778
TI  - Chemical dynamics simulations in the gas phase and on complex surfaces: a tribute
      to William Hase.

PMID- 16435781
TI  - Publications of William Hase.

PMID- 16435779
TI  - Autobiography of William Hase.

PMID- 16435782
TI  - Diels-Alder reactions of cyclopentadiene and 9,10-dimethylanthracene with
      cyanoalkenes: the performance of density functional theory and Hartree-Fock
      calculations for the prediction of substituent effects.
AB  - The activation enthalpies for the reactions of cyclopentadiene with ethylene,
      acrylonitrile, fumaronitrile, maleonitrile, vinylidene cyanide, tricyanoethylene,
      and tetracyanoethylene have been computed with the Hartree-Fock quantum
      mechanical method and a variety of density functionals (B3LYP, BPW91, and MPW1K)
      and compared to classic experimental data obtained by Sauer, Wiest, and Mielert
      (Chem. Ber. 1964, 97, 3183). Some significant errors in B3LYP activation
      enthalpies involving cyano groups, especially 3 or 4 cyano groups, have been
      identified, whereas HF and MPW1K reproduce substituent effects quite accurately.

PMID- 16435783
TI  - Quasiclassical trajectory study of the collision-induced dissociation dynamics of
      Ar + CH3SH+ using an ab initio interpolated potential energy surface.
AB  - Classical trajectory calculations have been performed to investigate the
      collision-induced dissociation (CID) of the CH(3)SH(+) cation with Ar atoms. A
      new intramolecular potential energy surface for the CH(3)SH(+) cation is
      evaluated by interpolation of 3000 ab initio data points calculated at the MP2/6
      311G(d,p) level of theory. The new potential energy surface includes seven
      accessible dissociation channels of the cation. The present QCT calculations show
      that migration of hydrogen atoms, leading to the rearrangement CH(3)SH(+) <-->
      CH(2)SH(2)(+), is significant at the collision energies considered (6.5-34.7 eV)
      and that the formation of CH(3)(+), CH(3)S(+), and CH(2)(+) cations takes place
      primarily by a "shattering" mechanism in which the products are formed just after
      the collision. The theoretical product abundances are found to be in qualitative
      agreement with the experimental data. However, at high collision energies, the
      calculated total cross sections for the formation of CH(3)(+) and CH(2)SH(+)
      cations are noticeably larger than the experimental determinations. Several
      features of the dynamics of the CID processes are discussed.

PMID- 16435784
TI  - Gas-phase reactions of carbon dioxide with atomic transition-metal and main-group
      cations: room-temperature kinetics and periodicities in reactivity.
AB  - The chemistry of carbon dioxide has been surveyed systematically with 46 atomic
      cations at room temperature using an inductively-coupled plasma/selected-ion flow
      tube (ICP/SIFT) tandem mass spectrometer. The atomic cations were produced at ca.
      5500 K in an ICP source and allowed to cool radiatively and to thermalize by
      collisions with Ar and He atoms prior to reaction downstream in a flow tube in
      helium buffer gas at 0.35 +/- 0.01 Torr and 295 +/- 2 K. Rate coefficients and
      products were measured for the reactions of first-row atomic ions from K(+) to
      Se(+), of second-row atomic ions from Rb(+) to Te(+) (excluding Tc(+)), and of
      third-row atomic ions from Cs(+) to Bi(+). CO(2) was found to react in a
      bimolecular fashion by O atom transfer only with 9 early transition-metal
      cations: the group 3 cations Sc(+), Y(+), and La(+), the group 4 cations Ti(+),
      Zr(+), and Hf(+), the group 5 cations Nb(+) and Ta(+), and the group 6 cation
      W(+). Electron spin conservation was observed to control the kinetics of O atom
      transfer. Addition of CO(2) was observed for the remaining 37 cations. While the
      rate of addition was not measurable some insight was obtained into the standard
      free energy change, DeltaG(o), for CO(2) ligation from equilibrium constant
      measurements. A periodic variation in DeltaG(o) was observed for first row
      cations that is consistent with previous calculations of bond energies D(0)(M(+)
      CO(2)). The observed trends in D(0) and DeltaG(o) are expected from the variation
      in electrostatic attraction between M(+) and CO(2) which follows the trend in
      atomic-ion size and the trend in repulsion between the orbitals of the atomic
      cations and the occupied orbitals of CO(2). Higher-order CO(2) cluster ions with
      up to four CO(2) ligands also were observed for 24 of the atomic cations while
      MO(2)(+) dioxide formation by sequential O atom transfer was seen only with
      Hf(+), Nb(+), Ta(+), and W(+).

PMID- 16435785
TI  - Guided-ion beam and theoretical study of the potential energy surface for
      activation of methane by W+.
AB  - A guided-ion beam tandem mass spectrometer is used to study the reactions, W(+) +
      CH(4) (CD(4)) and [W,C,2H](+) + H(2) (D(2)), to probe the [W,C,4H](+) potential
      energy surface. The reaction W(+) + CH(4) produces [W,C,2H](+) in the only low
      energy process. The analogous reaction in the CD(4) system exhibits a cross
      section with strong differences at the lowest energies caused by zero-point
      energy differences, demonstrating that this reaction is slightly exothermic for
      CH(4) and slightly endothermic for CD(4). The [W,C,2H](+) product ion reacts
      further at thermal energies with CH(4) to produce W(CH(2))(x)(+) (x = 2-4). At
      higher energies, the W(+) + CH(4) reaction forms WH(+) as the dominant ionic
      product with smaller amounts of WCH(3)(+), WCH(+), and WC(+) also formed. The
      energy dependent cross sections for endothermic formation of the various products
      are analyzed and allow the determination of D(0)(W(+)-CH(3)) approximately 2.31
      +/- 0.10 eV, D(0)(W(+)-CH(2)) = 4.74 +/- 0.03 eV, D(0)(W(+)-CH) = 6.01 +/- 0.28
      eV, and D(0)(W(+)-C) = 4.96 +/- 0.22 eV. We also examine the reverse reaction,
      [W,C,2H](+) + H(2) (D(2)) --> W(+) + CH(4) (CH(2)D(2)). Combining the cross
      sections for the forward and reverse processes yields an equilibrium constant
      from which D(0)(W(+)-CH(2)) = 4.72 +/- 0.04 eV is derived. Theoretical
      calculations performed at the B3LYP/HW+/6-311++G(3df,3p) level yield
      thermochemistry in reasonable agreement with experiment. These calculations help
      identify the structures and electronic states of the species involved and
      characterize the potential energy surface for the [W,C,4H](+) system.

PMID- 16435786
TI  - Simulating electron transfer attachment to a positively charged model peptide.
AB  - Ab initio electronic structure methods, including stabilization method tools for
      handling electronically metastable states, are used to treat a model system
      designed to probe the electron-transfer event characterizing electron-transfer
      dissociation (ETD) mass spectroscopic studies of peptides. The model system
      consists of a cation H(3)C-(C=O)NH-CH(2)-CH(2)-NH(3)(+), containing a protonated
      amine site and an amide site, that undergoes collisions with a CH(3)(-) anion.
      Cross-sections for electron transfer from CH(3)(-) to the protonated amine site
      are shown to exceed those for transfer to the Coulomb-stabilized amide site by 2
      orders of magnitude. Moreover, it is shown that the fates of the amine-attached
      and amide-attached species are similar in that both eventually lead to the same
      carbon-centered radical species H(3)C-((*)C-OH)NH-CH(2)-CH(2)-NH(2), although the
      reaction pathways by which the two species produce this radical are somewhat
      different. The implications for understanding peptide fragmentation patterns
      under ETD conditions are also discussed in light of this work's findings.

PMID- 16435787
TI  - Quasiclassical trajectory simulations of OH(v) + NO2 --> HONO2* --> OH(v') + NO2:
      capture and vibrational deactivation rate constants.
AB  - Quasiclassical trajectory calculations are used to investigate the dynamics of
      the OH(v) + NO(2) --> HONO(2) --> OH(v') + NO(2) recombination/dissociation
      reaction on an analytic potential energy surface (PES) that gives good agreement
      with the known structure and vibrational frequencies of nitric acid. The
      calculated recombination rate constants depend only weakly on temperature and on
      the initial vibrational energy level of OH(v). The magnitude of the recombination
      rate constant is sensitive to the potential function describing the newly formed
      bond and to the switching functions in the PES that attenuate inter-mode
      interactions at long range. The lifetime of the nascent excited HONO(2) depends
      strongly not only on its internal energy but also on the identity of the initial
      state, in disagreement with statistical theory. This disagreement is probably due
      to the effects of slow intramolecular vibrational energy redistribution (IVR)
      from the initially excited OH stretching mode. The vibrational energy
      distribution of product OH(v') radicals is different from statistical
      distributions, a result consistent with the effects of slow IVR. Nonetheless, the
      trajectory results predict that vibrational deactivation of OH(v) via the HONO(2)
      transient complex is approximately 90% efficient, almost independent of initial
      OH(v) vibrational level, in qualitative agreement with recent experiments. Tests
      are also carried out using the HONO(2) PES, but assuming the weaker O-O bond
      strength found in HOONO (peroxynitrous acid). In this case, the predicted
      vibrational deactivation efficiencies are significantly lower and depend strongly
      on the initial vibrational state of OH(v), in disagreement with experiments. This
      disagreement suggests that the actual HOONO PES may contain more inter-mode
      coupling than found in the present model PES, which is based on HONO(2). For
      nitric acid, the measured vibrational deactivation rate constant is a useful
      proxy for the recombination rate, but IVR randomization of energy is not
      complete, suggesting that the efficacy of the proxy method must be evaluated on a
      case-by-case basis.

PMID- 16435788
TI  - State-selective preparation of NO2+ and the effects of NO2+ vibrational mode on
      charge transfer with NO.
AB  - Two color resonance-enhanced multiphoton ionization (REMPI) scheme of NO(2)
      through the E (2)Sigma(u)(+) (3psigma) Rydberg state was used to prepare NO(2)(+)
      in its ground and (100), (010), (02(0)0), (02(2)0), and (001) vibrational states.
      Photoelectron spectroscopy was used to verify >96% state selection purity, in
      good agreement with results of Bell et al. for a similar REMPI scheme. The
      effects of NO(2)(+) vibrational excitation on charge transfer with NO have been
      studied over the center-of-mass collision energy (E(col)) range from 0.07 to 2.15
      eV. Charge transfer is strongly suppressed by collision energy at E(col) <
      approximately 0.25 eV but is independent of E(col) at higher energies. Mode
      specific vibrational effects are observed for both the integral and differential
      cross-sections. The NO(2)(+) bending vibration strongly enhances charge transfer,
      with enhancement proportional to the bending quantum number, and is not dependent
      on the bending angular momentum. The enhancement results from increased charge
      transfer probability in large impact parameter collisions that lead to small
      deflection angles. The symmetric stretch also enhances reaction at low collision
      energies, albeit less efficiently than the bend. The asymmetric stretch has
      virtually no effect, despite being the highest-energy mode. A model is proposed
      to account for both the collision energy and the vibrational state dependence.

PMID- 16435789
TI  - Stopped-flow kinetics of tetrazine cycloadditions; experimental and computational
      studies toward sequential transition states.
AB  - The Diels-Alder cycloadditions of tetrazines (1) with alkynes (2) are expected to
      give bicyclic adducts (3). Kinetic measurements of the cycloadditions of 1a and
      1b with 2a give DeltaG(++) = 19.2 +/- 1.0 and 11.5 +/- 1.2 kcal/mol,
      respectively. Stopped-flow UV studies on the reaction of 1b with 2a show an
      isosbestic point at 428 nm; this places an upper limit of 11.6 +/- 2.6 kcal/mol
      on DeltaG(++) for loss of N(2) from the putative bicyclic intermediate 3b.
      Calculations (B3LYP/6-31G(d,p) + ZPVE) of transition structures for the reaction
      of tetrazinediacid 1d with propynylamine 2c are consistent with the experimental
      results for the reaction of 1b with 2a. This and several related model systems
      reveal two interesting features of the calculated energy surfaces. First, there
      may be no barrier for the loss of nitrogen from structures 3 and thus there may
      be two sequential transition states. This also extends Berson's correlation of
      activation energy with reaction energy in pericyclic reactions to significantly
      lower barriers. Second, for the cycloaddition of 4e and 2c, there is neither an
      intermediate nor a transition state between TS3e and the final product 6e. It
      appears that the energy surface "turns a corner" in the vicinity of a structure
      resembling 5e. This is not a mathematically well-defined point but has chemical
      consequences in that the overall exothermicity of the reaction from 4e to 6e is
      not felt in TS3e.

PMID- 16435790
TI  - Coordinate covalent C --> B bonding in phenylborates and latent formation of
      phenyl anions from phenylboronic Acid.
AB  - The results are reported of a theoretical study of the addition of small
      nucleophiles Nu(-) (HO(-), F(-)) to phenylboronic acid Ph-B(OH)(2) and of the
      stability of the resulting complexes [Ph-B(OH)(2)Nu](-) with regard to Ph-B
      heterolysis [Ph-B(OH)(2)Nu](-) --> Ph(-) + B(OH)(2)Nu as well as Nu(-)/Ph(-)
      substitution [Ph-B(OH)(2)Nu](-) + Nu(-) --> Ph(-) + [B(OH)(2)Nu(2)](-). These
      reactions are of fundamental importance for the Suzuki-Miyaura cross-coupling
      reaction and many other processes in chemistry and biology that involve
      phenylboronic acids. The species were characterized by potential energy surface
      analysis (B3LYP/6-31+G*), examined by electronic structure analysis (B3LYP/6
      311++G**), and reaction energies (CCSD/6-311++G**) and solvation energies (PCM
      and IPCM, B3LYP/6-311++G*) were determined. It is shown that Ph-B bonding in [Ph
      B(OH)(2)Nu](-) is coordinate covalent and rather weak (<50 kcal.mol(-1)). The
      coordinate covalent bonding is large enough to inhibit unimolecular dissociation
      and bimolecular nucleophile-assisted phenyl anion liberation is slowed greatly by
      the negative charge on the borate's periphery. The latter is the major reason for
      the extraordinary differences in the kinetic stabilities of diazonium ions and
      borates in nucleophilic substitution reactions despite their rather similar
      coordinate covalent bond strengths.

PMID- 16435791
TI  - Optical excitations in carbon architectures based on
      dodecadehydrotribenzo[18]annulene.
AB  - The origin of excitations in multi-chromophore carbon network substructures based
      on dodecadehydrotribenzo[18]annulene has been investigated by steady-state and
      photon echo spectroscopy, configuration interaction (CIS and CIS(D)), and time
      dependent density functional theory (TD-DFT). 1,4-diphenylbutadiyne, the simplest
      structural subunit within the annulene, was used in modeling the spectroscopic
      studies to explain the origin of excitations in the macrocycles. The optical
      excitations in longer linear systems were found to be similar to its
      diphenylacetylene analogue. However, the results from
      dodecadehydrotribenzo[18]annulene and other multichromophore networks systems
      illustrate the possibility of strong intramolecular interactions and the
      formation of delocalized excited states. Calculations were carried out to explain
      the basic similarities and differences in excitations of the model compounds such
      as diphenylbutadiyne and the macrocycles. The fundamental excitation in these
      systems can be primarily described as a pi --> pi* transition. Two low-energy
      resonances were observed from experiment for the annulene systems, and possible
      explanations for these low-energy resonances in the macrocycles are explored. The
      significant difference found in the calculated oscillator strength of the two low
      energy bands for the macrocycles as well as the dynamics of solvent interactions
      was further investigated by three-pulse photon echo measurements. A simple
      exciton model was developed to discuss the excitations in the larger macrocycles.
      The results from this model were found to be in good agreement with the TD-DFT
      calculations.

PMID- 16435792
TI  - Theoretical study of the effect of surface density on the dynamics of Ar +
      alkanethiolate self-assembled monolayer collisions.
AB  - We present a classical-trajectory study of energy transfer in collisions of Ar
      atoms with alkanethiolate self-assembled monolayers (SAMs) of different
      densities. The density of the SAMs is varied by changing the distance between the
      alkanethiolate chains in the organic monolayers. Our calculations indicate that
      SAMs with smaller packing densities absorb more energy from the impinging Ar
      atoms, in agreement with recent molecular-beam scattering experiments. We find
      that energy transfer is enhanced by a decrease in the SAM density because (1)
      less dense SAMs increase the probability of multiple encounters between Ar and
      the SAM, (2) the vibrational frequencies of large-amplitude motions of the SAM
      chains decrease for less dense SAMs, which makes energy transfer more efficient
      in single-encounter collisions, and (3) increases in the distance between chains
      promote surface penetration of the Ar atom. Analysis of angular distributions
      reveals that the polar-angle distributions do not have a cosine shape in trapping
      desorption processes involving penetration of the Ar atom into the alkanethiolate
      self-assembled monolayers. Instead, there is a preference for Ar atoms that
      penetrate the surface to desorb along the chain-tilt direction.

PMID- 16435793
TI  - Experimental and theoretical investigations of the inelastic and reactive
      scattering dynamics of O(3p) + D2.
AB  - This paper presents a combined experimental and theoretical study of the dynamics
      of O((3)P) + D(2) collisions, with emphasis on a center-of-mass (c.m.) collision
      energy of 25 kcal mol(-1). The experiments were conducted with a crossed
      molecular-beams apparatus, employing a laser detonation source to produce
      hyperthermal atomic oxygen and mass spectrometric detection to measure the
      product angular and time-of-flight distributions. The novel beam source, which
      enabled these experiments to be conducted, contributed unique challenges to the
      experiments and to the analysis, so the experimental methods and approach to the
      analysis are discussed in detail. Three different levels of theory were used: (1)
      quasiclassical trajectories (QCT), (2) time-independent quantum scattering
      calculations based on high-quality potential surfaces for the two lower-energy
      triplet states, and (3) trajectory-surface-hopping (TSH) studies that couple the
      triplet surfaces with the lowest singlet surface using a spin-orbit Hamiltonian
      derived from ab-initio calculations. The latter calculations explore the
      importance of intersystem crossing in the dynamics. Both experiment and theory
      show that inelastically scattered O atoms scatter almost exclusively in the
      forward direction, with little or no loss of translational energy. For the
      reaction, O((3)P) + D(2) --> OD + D, the experiment shows that, on average,
      approximately 50% of the available energy goes into product translation and that
      the OD product angular distributions are largely backward-peaked. These results
      may be interpreted in light of the QCT and TSH calculations, leading to the
      conclusion that the reaction occurs mainly on triplet potential energy surfaces
      with, at most, minor intersystem crossing to a singlet surface. Reaction on
      either of the two low-lying reactive triplet surfaces proceeds through a rebound
      mechanism in which the angular distributions are backward-peaked and the product
      OD is both vibrationally and rotationally excited. The quantum scattering results
      are in good agreement with QCT calculations, indicating that quantum effects are
      relatively small for this reaction at a collision energy of 25 kcal mol(-1).

PMID- 16435794
TI  - Collision-induced dissociation of HS-(HCN): unsymmetrical hydrogen bonding in a
      proton-bound dimer anion.
AB  - The energy-resolved competitive collision-induced dissociation of the proton
      bound complex [HS.H.CN](-) is studied in a guided ion beam tandem mass
      spectrometer. H(2)S and HCN have nearly identical gas-phase acidities, and
      therefore, the HS(-) + HCN and the CN(-) + H(2)S product channels exhibit nearly
      the same threshold energies, as expected. However, the HS(-) + HCN channel has a
      cross section up to a factor of 50 larger than CN(-) + H(2)S at higher energies.
      The cross sections are modeled using RRKM theory and phase space theory. The
      complex dissociates to HS(-)+ HCN via a loose transition state, and it
      dissociates to CN(-) + H(2)S via a tight transition state. Theoretical
      calculations show that the proton-transfer potential energy surface has a single
      minimum and that the hydrogen bonding in the complex is strongly unsymmetrical,
      with an ion-molecule complex of the form HS(-)..HCN rather than CN(-)..H(2)S or
      an intermediate structure. The requirement for proton transfer before
      dissociation and curvature along the reaction path impedes the CN(-) + H(2)S
      product channel.

PMID- 16435795
TI  - Gas phase SN2 reactions of halide ions with trifluoromethyl halides: front- and
      back-side attack vs. complex formation.
AB  - Density functional theory computations and pulsed-ionization high-pressure mass
      spectrometry experiments have been used to explore the potential energy surfaces
      for gas-phase S(N)2 reactions between halide ions and trifluoromethyl halides, X(
      ) + CF(3)Y --> Y(-) + CF(3)X. Structures of neutrals, ion-molecule complexes, and
      transition states show the possibility of two mechanisms: back- and front-side
      attack. From pulsed-ionization high-pressure mass spectrometry, enthalpy and
      entropy changes for the equilibrium clustering reactions for the formation of Cl(
      )(BrCF(3)) (-16.5 +/- 0.2 kcal mol(-1) and -24.5 +/- 1 cal mol(-1) K(-1)), Cl(
      )(ICF(3)) (-23.6 +/- 0.2 kcal mol(-1)), and Br(-)(BrCF(3)) (-13.9 +/- 0.2 kcal
      mol(-1) and -22.2 +/- 1 cal mol(-1) K(-1)) have been determined. These are in
      good to excellent agreement with computations at the B3LYP/6-311+G(3df)//B3LYP/6
      311+G(d) level of theory. It is shown that complex formation takes place by a
      front-side attack complex, while the lowest energy S(N)2 reaction proceeds
      through a back-side attack transition state. This latter mechanism involves a
      potential energy profile which closely resembles a condensed phase S(N)2 reaction
      energy profile. It is also shown that the Cl(-) + CF(3)Br --> Br(-) + CF(3)Cl
      S(N)2 reaction can be interpreted using Marcus theory, in which case the reaction
      is described as being initiated by electron transfer. A potential energy surface
      at the B3LYP/6-311+G(d) level of theory confirms that the F(-) + CF(3)Br --> Br(
      ) + CF(4) S(N)2 reaction proceeds through a Walden inversion transition state.

PMID- 16435796
TI  - Theoretical study of ultrafast heterogeneous electron transfer reactions at dye
      semiconductor interfaces: coumarin 343 at titanium oxide.
AB  - A theoretical study of photoinduced heterogeneous electron transfer in the dye
      semiconductor system coumarin 343-TiO(2) is presented. The study is based on a
      generic model for heterogeneous electron transfer reactions, which takes into
      account the coupling of the electronic states to the nuclear degrees of freedom
      of coumarin 343 as well as to the surrounding solvent. The quantum dynamics of
      the electron injection process is simulated employing the recently proposed
      multilayer formulation of the multiconfiguration time-dependent Hartree method.
      The results reveal an ultrafast injection dynamics of the electron from the
      photoexcited donor state into the conduction band of the semiconductor.
      Furthermore, the mutual influence of electronic injection dynamics and nuclear
      motion is analyzed in some detail. The analysis shows that--depending on the time
      scale of nuclear motion--electronic vibrational coupling can result in electron
      transfer driven by coherent vibrational motion or vibrational motion induced by
      ultrafast electron transfer.

PMID- 16435797
TI  - Molecular determinants for binding of ammonium ion in the ammonia transporter
      AmtB-A quantum chemical analysis.
AB  - The transport of ammonium across the cell membrane represents an important
      biological process in all living organisms. The mechanisms for ammonium
      translocation were analyzed by computer simulations based on first principles.
      Intermolecular interaction energies between the differentially methylated
      ammonium and the ammonium channel protein AmtB were calculated by means of the
      supermolecular approach at the MP2/6-311+G* level based on the high-resolution
      crystal structures of ligand-bound protein complexes. Our analysis attributes the
      molecular determinants for protein-ligand recognition in ammonium transporter
      AmtB to the aromatic cage formed by three aromatic residues Phe103, Phe107, and
      Trp148, as well as Ser219. The former residues are involved in cation-pi
      interactions with the positively charged methylated ammoniums. The latter residue
      acts as a hydrogen bond acceptor to ammonium. Thus, this work provides directly
      the missing evidence for the hypothesized role played by the wider vestibule site
      of AmtB at the periplasmic side of the membrane in "recruiting" NH(4)(+) or
      methylammonium ions as proposed by Khademi et al. (Science 2004, 305, 1587). In
      addition, a hybrid quantum mechanics/molecular mechanics scheme was applied to
      optimize the structures of differentially methylated ammoniums in the AmtB
      protein, which generated structural and energetic data that provide a
      satisfactory explanation to the experimental observation that tetramethylammonium
      is not inhibitory to conducting ammonium and methylammonium in the ammonium
      transport channel.

PMID- 16435798
TI  - Measuring the size dependence of Young's modulus using force modulation atomic
      force microscopy.
AB  - The dependence of the local Young's modulus of organic thin films on the size of
      the domains at the nanometer scale is systematically investigated. Using atomic
      force microscopy (AFM) based imaging and lithography, nanostructures with
      designed size, shape, and functionality are preengineered, e.g., nanostructures
      of octadecanethiols inlaid in decanethiol self-assembled monolayers (SAMs). These
      nanostructures are characterized using AFM, followed by force modulation
      spectroscopy and microscopy measurements. Young's modulus is then extracted from
      these measurements using a continuum mechanics model. The apparent Young's
      modulus is found to decrease nonlinearly with the decreasing size of these
      nanostructures. This systematic study presents conclusive evidence of the size
      dependence of elasticity in the nanoregime. The approach utilized may be applied
      to study the size-dependent behavior of various materials and other mechanical
      properties.

PMID- 16435799
TI  - Sputtering of water ice induced by C60 bombardment: onset of plume formation.
AB  - The interaction of a 5 keV C(60) projectile with amorphous water ice is studied
      using molecular dynamics computer simulations. The energetic C(60) molecule
      causes large-scale collisional events in the subsurface region, involving more
      than 10(4) water molecules in a time of less than 3 ps. The energy deposited in
      the sample is sufficiently large to turn the ice into a superheated and
      superdense gas. The gas is expelled into the vacuum, leading to the formation of
      a flow that manifests itself in the angular and velocity distributions of emitted
      water molecules.

PMID- 16435800
TI  - Insight into selected reactions in low-temperature dimethyl ether combustion from
      Born-Oppenheimer molecular dynamics.
AB  - Dimethyl ether is under consideration as an alternative diesel fuel. Its
      combustion chemistry is as yet ill-characterized. Here we use Born-Oppenheimer
      molecular dynamics (BOMD) based on DFT-B3LYP forces to investigate the short-time
      dynamics of selected features of the low-temperature dimethyl ether (DME)
      oxidation potential energy surface. Along the chain propagation pathway, we run
      BOMD simulations from the transition state involving the decomposition of
      (*)CH(2)OCH(2)OOH to two CH(2)=O and an (*)OH radical. We predict that
      formaldehyde C-O stretch overtones are excited, consistent with laser photolysis
      experiments. We also predict that O-H overtones are excited for the (*)OH formed
      from (*)CH(2)OCH(2)OOH dissociation. We also investigate short-time dynamics
      involved in chain branching. First, we examine the isomerization transition state
      of (*)OOCH(2)OCH(2)OOH --> HOOCH(2)OCHOOH. The latter species is predicted to be
      a short-lived metastable radical that decomposes within 500 fs to
      hydroperoxymethyl formate (HPMF; HOOCH(2)OC(=O)H) and the first (*)OH of chain
      branching. The dissociation of HOOCH(2)OCHOOH exhibits non-RRKM behavior in its
      lifetime profile, which may be due to conformational constraints or slow
      intramolecular vibrational energy transfer (IVR) from the nascent H-O bond to the
      opposite end of the radical, where O-O scission occurs to form HPMF and (*)OH. In
      a few trajectories, we see HOOCH(2)OCHOOH recross back to (*)OOCH(2)OCH(2)OOH
      because the isomerization is endothermic, with only an 8 kcal/mol barrier to
      recrossing. Therefore, some inhibition of chain-branching may be due to
      recrossing. Second, trajectories run from the transition state leading to the
      direct decomposition of HPMF (an important source of the second (*)OH radical in
      chain branching) to HCO, (*)OH, and HC(=O)OH show that these products can
      recombine to form many other possible products. These products include CH(2)OO +
      HC(=O)OH, H(2)O + CO + HC(=O)OH, HC(=O)OH + HC(=O)OH, and HC(=O)C(=O)H + H(2)O,
      which (save CH(2)OO + HC(=O)OH) are all more thermodynamically stable than the
      original HCO + (*)OH + HC(=O)OH products. Moreover, the multitude of extra
      products suggest that standard statistical rate theories cannot completely
      describe the reaction kinetics of significantly oxygenated compounds such as
      HPMF. These secondary products consume the second (*)OH required for explosive
      combustion, suggesting an inhibition of DME fuel combustion is likely.

PMID- 16435801
TI  - Reaction of 5-40 eV ions with self-assembled monolayers.
AB  - The reaction of 5-40 eV O(+) and Ne(+) ions with alkanethiolate and
      semifluorinated alkanethiolate self-assembled monolayers (SAMs) is studied under
      ultrahigh vacuum (UHV) conditions. Whereas Ne(+) simply sputters fragments from
      the surface, O(+) can also abstract surface atoms and break C-C bonds in both the
      hydrocarbon and fluorocarbon SAM chains. Isotopic labeling experiments reveal
      that O(+) initially abstracts hydrogen atoms from the outermost two carbon atoms
      on an alkanethiolate SAM chain. However, the position of the isotopic label
      quickly becomes scrambled along the chain as the SAM is damaged through
      continuous ion bombardment. Scanning tunneling microscopy (STM) monitors changes
      in the SAM conformational structure at various stages during 5 eV ion
      bombardment. STM images indicate that O(+) reacts less efficiently with
      dodecanethiolate molecules packed internally within a structural domain than it
      does with molecules adsorbed at domain boundaries or near defect sites. STM
      images recorded after Ne(+) bombardment suggest that Ne(+) attacks the SAM
      exclusively near the domain boundaries. Taken collectively, these experiments
      advance our understanding of the degradation pathways suffered by polymeric
      satellite materials in the low-earth orbit (LEO) space environment.

PMID- 16435802
TI  - Do B3LYP and CCSDT predict different hydrosilylation mechanisms? Influences of
      theoretical methods and basis sets on relative energies in ruthenium-silylene
      catalyzed ethylene hydrosilylation.
AB  - A series of density functional theory (DFT) and wave function theory (WFT)
      methods were used in conjunction with a series of basis sets to investigate the
      influence of the computational methodology on the relative energies of key
      intermediates and transition states in potential reaction pathways in ruthenium
      silylene-catalyzed hydrosilylation reactions. A variety of DFT methods in a
      modest basis set and B3LYP calculations in a variety of basis sets calculated the
      key transition in the Glaser-Tilley (GT) pathway to be energetically favored. In
      contrast, with the smaller basis sets, the CCSD(T) method calculated the Chalk
      Harrod (CH) pathway to be favored; however, CCSD(T) results extrapolated to
      larger basis sets favored the GT pathway.

PMID- 16435803
TI  - Sodium cation affinities of MALDI matrices determined by guided ion beam tandem
      mass spectrometry: application to benzoic acid derivatives.
AB  - Threshold collision-induced dissociation of Na(+)(xBA) complexes with Xe is
      studied using guided ion beam mass spectrometry. The xBA ligands studied include
      benzoic acid and all of the mono- and dihydroxy-substituted benzoic acids: 2-, 3
      , and 4-hydroxybenzoic acid and 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5
      dihydroxybenzoic acid. In all cases, the primary product corresponds to
      endothermic loss of the intact xBA ligand. The cross section thresholds are
      interpreted to yield 0 and 298 K bond dissociation energies (BDEs) for Na(+)-xBA
      after accounting for the effects of multiple ion-neutral collisions, internal and
      kinetic energy distributions of the reactants, and dissociation lifetimes.
      Density functional theory calculations at the B3LYP/6-31G* level of theory are
      used to determine the structures of these complexes and provide the molecular
      constants necessary for the thermodynamic analysis of the experimental data.
      Theoretical BDEs are determined at the B3LYP/6-311+G(2d,2p) and MP2(full)/6
      311+G(2d,2p) levels using the B3LYP/6-31G* optimized geometries. The trends in
      the measured BDEs suggest two very different binding modes for the Na(+)(xBA)
      complexes, while theory finds four. In general, the most stable binding
      conformation involves the formation of a six-membered chelation ring via
      interaction with the carbonyl and 2-hydroxyl oxygen atoms. The ground state
      geometries of the Na(+)(xBA) complexes in which the ligand does not possess a 2
      hydroxyl group generally involve binding of Na(+) to either the carbonyl oxygen
      atom or to both oxygen atoms of the carboxylic acid group. These binding modes
      tend to be competitive because the enhancement in binding associated with the
      chelation interactions in the latter is mediated by steric repulsion between the
      hydroxyl and ortho hydrogen atoms. When possible, hydrogen bonding interactions
      with the ring hydroxyl group(s) enhance the stability of these complexes. The
      agreement between the theoretical and experimental BDEs is quite good for B3LYP
      and somewhat less satisfactory for MP2(full).

PMID- 16435805
TI  - Influence of thioketo substitution on the properties of uracil and its
      noncovalent interactions with alkali metal ions: threshold collision-induced
      dissociation and theoretical studies.
AB  - Experimental and theoretical studies are carried out to determine the influence
      of thioketo substitution on the properties of uracil and its noncovalent
      interactions with alkali metal ions. Bond dissociation energies of alkali metal
      ion-thiouracil complexes, M(+)(SU), are determined using threshold collision
      induced dissociation techniques in a guided ion beam mass spectrometer, where
      M(+) = Li(+), Na(+), and K(+) and SU = 2-thiouracil, 4-thiouracil, 2,4
      dithiouracil, 5-methyl-2-thiouracil, and 6-methyl-2-thiouracil. Ab initio
      electronic structure calculations are performed to determine the structures and
      theoretical bond dissociation energies of these complexes and provide molecular
      constants necessary for thermodynamic analysis of the experimental data.
      Theoretical calculations are also performed to examine the influence of thioketo
      substitution on the acidities, proton affinities, and A::SU Watson-Crick base
      pairing energies. In general, thioketo substitution leads to an increase in both
      the proton affinity and the acidity of uracil. 2-Thio substitution generally
      results in an increase in the alkali metal ion binding affinities but has almost
      no affect on the stability of the A::SU base pair. In contrast, 4-thio
      substitution results in a decrease in the alkali metal ion binding affinities and
      a significant decrease in the stability of the A::SU base pair. In addition,
      alkali metal ion binding is expected to lead to an increase in the stability of
      both single-stranded and double-stranded nucleic acids by reducing the charge on
      the nucleic acid in a zwitterion effect as well as through additional noncovalent
      interactions between the alkali metal ion and the nucleobases.

PMID- 16435804
TI  - Nonadiabatic trajectory studies of NaI(H2O)n photodissociation dynamics.
AB  - We have investigated the photodissociation dynamics of NaI(H(2)O)(n) [n = 1-4]
      clusters using the molecular dynamics with quantum transitions method and a
      quantum mechanics/molecular mechanics description of NaI(H(2)O)(n), which
      involves a semiempirical valence-bond approach to describe the NaI electronic
      structure and classical solvent-solvent and solute-solvent interaction
      potentials. Our simulation results show that the NaI(H(2)O)(n) excited-state
      population decay upon reaching the NaI curve-crossing region increases with
      cluster size due to the stabilization of the ionic branch of the NaI excited
      state by the surrounding water molecules, and the resulting increase in
      nonadiabatic transition probability. After reaching the curve-crossing region for
      the first time, however, the excited-state population decay resembles that of
      bare NaI because of rapid evaporation of 99% and 95% of the water molecules for
      NaI(H(2)O) and NaI(H(2)O)(n) [n = 2-4], respectively. This extensive evaporation
      is due to the reversed NaI polarity in the Franck-Condon region of the NaI first
      excited state, which causes strong repulsive NaI-H(2)O forces and induces rapid
      nonstatistical water evaporation, where product water molecules are formed more
      rotationally than translationally hot. A few water molecules (5% or less) remain
      transiently or permanently bound to NaI, forming long-lived clusters, when NaI
      remains predominantly ionic, i.e., remains in the excited state, after reaching
      the curve-crossing region. To connect simulation results with experiment, we have
      simulated femtosecond probe signals resulting from two-photon and one-photon
      excitation to the X and I NaI(+) probe states. In agreement with experimental
      findings, the probe signals resulting from the two-photon probe scheme, where
      excitation occurs from the covalent branch of the excited state, decay
      exponentially over the NaI first excited-state vibrational period, with very
      little evidence of long-time dynamics. The one-photon probe scheme (not used for
      experimental cluster studies) is shown to be less sensitive to solvation, in that
      excitation energies will remain similar over a range of cluster sizes, as the
      ionic branch of the excited state and the NaI(+) probe states are stabilized to
      the same extent by the presence of water molecules. The resulting probe signals
      are also more revealing of the NaI(H(2)O)(n) photodissociation dynamics than the
      two-photon probe signals, as they may allow monitoring of solvation effects on
      the NaI nonadiabatic dynamics and of successive evaporation of water molecules.
      Time-resolved photoelectron spectra provide limited additional information
      regarding the NaI(H(2)O)(n) photodissociation dynamics. A key consequence of the
      rapid water evaporation demonstrated here is that experimentally observed signals
      may arise from the photodissociation of much larger NaI(H(2)O)(n) parent
      clusters.

PMID- 16435806
TI  - Experiments and simulations of hyperthermal Xe interacting with an ordered 1
      decanethiol/Au(111) monolayer: penetration followed by high-energy, directed
      ejection.
AB  - A study of the interaction of hyperthermal Xe with a well-ordered standing-up
      phase of 1-decanethiol adsorbed on Au(111) is presented. Experimentally, double
      differential measurements were made of the postcollision Xe kinetic energy as a
      function of incident and final angles. These experiments are compared to
      classical trajectory calculations. The results show the two expected channels:
      direct-inelastic scattering from the surface and accommodated Xe due to trapping
      desorption. There is also evidence of a further interaction mechanism. This
      involves the penetration of the atom deep into the channels between the aligned
      chains of the monolayer. When the collision energy has been dissipated, the
      implanted Xe is expelled as the chains return to their equilibrium positions. The
      expelled Xe leaves the surface with an energy much higher than expected for
      trapping-desorption, and with an angular-intensity distribution peaked close to
      the direction of the 1-decanethiol chain orientation. For this reason, we call
      this new scattering mechanism directed ejection.

PMID- 16435807
TI  - High resolution electronic spectra of anisole and anisole-water in the gas phase:
      hydrogen bond switching in the S1 state.
AB  - Rotationally resolved S(1)<--S(0) electronic spectra of anisole and its hydrogen
      bonded complex containing one water molecule have been obtained. The results
      provide evidence for an "in-plane" complex in which the water molecule is
      attached via two hydrogen bonds to the anisole molecule, a donor O-H- - -O(CH(3))
      bond and an acceptor H-O- - -H(ring) bond. Analysis of the subbands that appear
      in the spectrum of the complex suggests that hydrogen bond "switching" occurs
      when the complex absorbs light. The former O-H- - -O(CH(3)) bond is stronger in
      the ground (S(0)) state, whereas the latter H-O- - -H(ring) bond is stronger in
      the excited (S(1)) state. Dynamical consequences of this phenomenon are
      discussed.

PMID- 16435808
TI  - Comparison of levels of electronic structure theory in direct dynamics
      simulations of C2H5F --> HF + C2H4 product energy partitioning.
AB  - Direct dynamics simulations at the MP2/6-311++G** level of theory were performed
      to study C(2)H(5)F --> HF + C(2)H(4) product energy partitioning. The simulation
      results are compared with experiment and a previous MP2/6-31G* simulation. The
      current simulation with the larger basis set releases more energy to HF vibration
      and less to HF + C(2)H(4) relative translation as compared to the previous
      simulation with the 6-31G* basis set. The HF rotation and vibration energy
      distributions determined from the current simulation are in overall very good
      agreement with previous experimental studies of C(2)H(5)F dissociation by
      chemical activation and IRMPA. A comparison of the simulations with experiments
      suggests there may be important mass effects for energy partitioning in HX
      elimination from haloalkanes. The transition state (TS) structures and energies
      calculated with MP2 and the 6-31G* and 6-311++G** basis sets are compared with
      those calculated using CCD, CCSD, CCSD(T), and the 6-311++G** basis set.

PMID- 16435809
TI  - On the model dependence of kinetic shifts in unimolecular reactions: the
      dissociation of the cations of benzene and n-butylbenzene.
AB  - Statistical adiabatic channel model/classical trajectory (SACM/CT) calculations
      have been performed for transitional mode dynamics in the simple bond fission
      reactions of C(6)H(6)(+) --> C(6)H(5)(+) + H and n-C(6)H(5)C(4)H(9)(+) -->
      C(7)H(7)(+) + n-C(3)H(7). Reduced-dimensionality model potentials have been
      designed that take advantage of ab initio results as far as available. Average
      anisotropy amplitudes of the potentials were fitted by comparison of calculated
      specific rate constants k(E,J) with measured values. The kinetic shifts of the
      calculated k(E) curves and the corresponding bond energies E(0)(J=0), derived as
      3.90 +/- 0.05 eV for C(6)H(6)(+) and 1.78 +/- 0.05 eV for n-C(6)H(5)C(4)H(9)(+),
      were in good agreement with literature values from thermochemical studies.
      Kinetic shifts from fixed tight activated complex Rice-Ramsperger-Kassel-Marcus
      (RRKM) theory, which also reproduces the measured k(E), were larger than the
      present SACM/CT results as well as earlier results from variational transition
      state theory (for C(6)H(6)(+)). The approach using RRKM theory was found to
      underestimate E(0)(J=0) by about 0.2-0.3 eV. A simplified SACM/CT-based method is
      also proposed which circumvents the trajectory calculations and allows derivation
      of E(0)(J=0) on the basis of measured k(E) and which provides similar accuracy as
      the full SACM/CT treatment.

PMID- 16435810
TI  - Laser ablation of imidazolium based ionic liquids.
AB  - Time-of-flight mass spectrometry has been used to investigate the IR ablation of
      several ionic liquid imidazolium salts of the form R(1)R(2)Iium X (R(1) = methyl;
      R(2) = methyl, ethyl, butyl, and hexyl; X = Cl(-), NO(3)(-), and CH(3)SO(4)(-)).
      The ablated ionic species were analyzed by time-of-flight mass spectrometry using
      pulsed extraction, and neutral species were detected using vacuum UV
      photoionization at 10.5 eV. The results demonstrate that at least 99% of the
      ablated material is removed in the form of nano- or microdroplets consisting of
      intact ionic liquid. Approximately 1% is ejected as imidazole molecules
      (R(1)R(2)Im) produced through the elimination of HCl, and about 0.1% of the
      material is ejected in the form of single salt molecules of R(1)R(2)Iium X. A
      chemical thermometer was used to measure the internal temperature (475 +/- 25 K)
      of the ablated vapor plume.

PMID- 16435811
TI  - Rate constants and kinetic isotope effects for unimolecular 1,2-HX or DX (X = F
      or Cl) elimination from chemically activated CF3CFClCH3-d0, -d1, -d2, and -d3.
AB  - Chemically activated CF(3)CFClCH(3), CF(3)CFClCD(3), CF(3)CFClCH(2)D, and
      CF(3)CFClCHD(2) molecules with 94 kcal mol(-1) of internal energy were formed by
      the combination of CF(3)CFCl radicals with CH(3), CD(3), CH(2)D, and CHD(2)
      radicals, which were generated from UV photolysis of CF(3)CFClI and CH(3)I,
      CD(3)I, CH(2)DI, or CHD(2)I. The total (HF + HCl) elimination rate constants for
      CF(3)CFClCH(3) and CF(3)CFClCD(3) were 5.3 x 10(6) and 1.7 x 10(6) s(-1) with
      product branching ratios of 8.7 +/- 0.6 in favor of HCl (or DCl). The
      intermolecular kinetic isotope effects were 3.22 and 3.18 for the HCl and HF
      channels, respectively. The product branching ratios were 10.3 +/- 1.9 and 11.8
      +/- 1.8 (10.8 +/- 3.8 and 11.6 +/- 1.7) for HCl/HF and DCl/DF, respectively, from
      CF(3)CFClCH(2)D (CF(3)CFClCHD(2)). The intramolecular kinetic-isotope effects
      (without correction for reaction path degeneracy) for HCl/DCl and HF/DF
      elimination from CF(3)CFClCH(2)D (CF(3)CFClCHD(2)) were 2.78 +/- 0.16 and 2.98 +/
      0.12 (0.82 +/- 0.04 and 0.91 +/- 0.03), respectively. Density function theory at
      the B3PW91/6-311+G(2d,p) and B3PW91/6-31G(d',p') levels was investigated, and the
      latter was chosen to calculate frequencies and moments of inertia for the
      molecules and transition states. Rate constants, branching ratios and kinetic
      isotope effects then were calculated using RRKM theory with torsional motions
      treated as hindered internal rotations. Threshold energies for HF and HCl
      elimination from CF(3)CFClCH(3) were assigned as 61.3 +/- 1.5 and 58.5 +/- 1.5
      kcal mol(-1), respectively. The threshold energy for Cl-F interchange was
      estimated as 67 kcal mol(-1). The difference between the transition states for
      HCl and HF elimination is discussed.

PMID- 16435812
TI  - Molecular dynamics simulations of the melting of aluminum nanoparticles.
AB  - Molecular dynamics simulations are performed to determine the melting points of
      aluminum nanoparticles of 55-1000 atoms with the Streitz-Mintmire [Phys. Rev. B
      1994, 50, 11996] variable-charge electrostatic plus potential. The melting of the
      nanoparticles is characterized by studying the temperature dependence of the
      potential energy and Lindemann index. Nanoparticles with less than 850 atoms show
      bistability between the solid and liquid phases over temperature ranges below the
      point of complete melting. The potential energy of a nanoparticle in the bistable
      region alternates between values corresponding to the solid and liquid phases.
      This bistability is characteristic of dynamic coexistence melting. At higher
      temperatures, only the liquid state is stable. Nanoparticles with more than 850
      atoms undergo a sharp solid-liquid-phase transition characteristic of the bulk
      solid phase. The variation of the melting point with the effective nanoparticle
      radius is also determined.

PMID- 16435813
TI  - Rotating-top approximation in reduced-dimensionality quantum calculations of rate
      constants: application to complex-forming nucleophilic substitution.
AB  - Within the framework of reduced-dimensionality quantum scattering theory, we
      employ Bowman's adiabatic rotation approximation to describe reactive systems
      that have symmetric-top geometries during the entire collision process. The
      results are compared with the approach of shifting the total energy by a
      characteristic rotational energy. Initial state-selected and total thermal rate
      constants have been computed for the complex-forming gas-phase reaction Cl(-) +
      CH(3)Cl' --> ClCH(3) + Cl'(-). At room temperature, we find a significant
      contribution from energetically high vibrational modes. The dependence of the
      cross-sections on the different angular momenta is analyzed in detail, and high
      total angular momenta are found to be of considerable importance. The influence
      of adiabatic azimuthal rotation on the rate constants turns out to be small
      compared to other effects. In addition, we use a new model to account for the
      asymmetric modes not explicitly contained in the scattering calculations. The
      difference to the only available experimental value confirms our conclusion that
      the Cl-C-Cl' bending modes are of major importance for this reaction.

PMID- 16435814
TI  - Quantum mechanical rate constants for H + O2 <--> O + OH and H + O2 --> HO2
      reactions.
AB  - Canonical rate constants for both the forward and reverse H + O(2) <--> O + OH
      reactions were calculated using a quantum wave packet-based statistical model on
      the DMBE IV potential energy surface of Varandas and co-workers. For these
      bimolecular reactions, the results show reasonably good agreement with available
      experimental and theoretical data up to 1500 K. In addition, the capture rate for
      the H + O(2) --> HO(2) addition reaction at the high-pressure limit was obtained
      on the same potential using a time-independent quantum capture method. Excellent
      agreement with experimental and quasi-classical trajectory results was obtained
      except for at very low temperatures, where a reaction threshold was found and
      attributed to the centrifugal barrier of the orbital motion.

PMID- 16435815
TI  - Energy transfer between polyatomic molecules II: Energy transfer quantities and
      probability density functions in benzene, toluene, p-xylene, and azulene
      collisions.
AB  - Collisional energy transfer, CET, is of major importance in chemical,
      photochemical, and photophysical processes in the gas phase. In Paper I of this
      series (J. Phys. Chem. B 2005, 109, 8310) we have reported on the mechanism and
      quantities of CET between an excited benzene and cold benzene and Ar bath. In the
      present work, we report on CET between excited toluene, p-xylene, and azulene
      with cold benzene and Ar and on CET of excited benzene with cold toluene, p
      xylene, and azulene. We compare our results with those of Paper I and report
      average vibrational, rotational, and translational energy quantities, <DeltaE>,
      transferred in a single collision. We discuss the effect of internal rotation on
      CET and the identity of the gateway modes in CET and the relative role of
      vibrational, rotational, and translational energies in the CET process, all that
      as a function of temperature and excitation energy. Energy transfer probability
      density functions, P(E,E'), for the various systems are reported and the shape of
      the curves for various systems and initial conditions is discussed. The major
      findings for polyatomic-polyatomic collisions are: CET takes place mainly via
      vibration-to-vibration energy transfer assisted by overall rotations. Internal
      free rotors in the excited molecule hinder energy exchange while in the bath
      molecule they do not. Energy transfer at low temperatures and high temperatures
      is more efficient than that at intermediate temperatures. Low-frequency modes are
      the gateway modes for energy transfer. Vibrational temperatures affect energy
      transfer. The CET probability density function, P(E,E'), is convex at low
      temperatures and can be concave at high temperatures. A mechanism that explains
      the high values of <DeltaE(a)> and the convex shape of P(E,E') is that in
      addition to short impulsive collisions there are chattering collisions where
      energy is transferred in a sequence of short encounters during the lifetime of
      the collision complex. This also leads to the observed supercollision tail at the
      down wing of P(E,E'). Polyatomic-Ar collisions show mechanistic similarities to
      polyatomic-polyatomic collisions, but there are also many dissimilarities:
      internal rotations do not inhibit energy transfer, P(E,E') is concave at all
      temperatures, and there is no contribution of chattering collisions.

PMID- 16435816
TI  - Validity of phase space theory for atom-diatom insertion reactions.
AB  - Phase space theory (PST) is applied to the calculation of state-resolved integral
      and differential cross sections for the complex-forming atom-diatom insertion
      reactions A + H(2) --> AH(2) --> AH + H with A = C((1)D), S((1)D), O((1)D), and
      N((2)D). In the asymptotic channels, vibration motion is quantized while rotation
      and translation motions are treated classically. The approach is compared to
      exact quantum scattering calculations and quantum statistical models. Given the
      simplicity of PST, the agreement with the previous much more refined treatments
      is very satisfying. Although PST is a well-established theory, this work is, to
      our knowledge, the first such systematic comparison of its predictions with
      accurate quantum scattering and quantum statistical calculations.

PMID- 16435817
TI  - Temperature measurement from the translational kinetic energy release
      distribution in cluster dissociation: a theoretical investigation.
AB  - Unimolecular dissociation of neutral and charged argon clusters is theoretically
      investigated in the context of calorimetric measurements. The temperature of the
      product cluster is estimated from the distribution of the translational kinetic
      energy released (KER), assumed to have the form f(epsilon) approximately
      epsilon(alpha) exp(-epsilon/k(B)T). Phase space theory (PST) in its orbiting
      transition state (OTS) version is validated by comparing its predictions to the
      results of large-scale molecular dynamics simulations. The temperatures estimated
      from the KER distributions are seen to be generally lower than the actual
      microcanonical temperature computed from independent Monte Carlo simulations of
      the product cluster at thermal equilibrium. On the basis of these deviations, the
      various approximations leading from the rigorous PST/OTS treatment to the assumed
      exponential form are critically discussed. In the case of Ar(n)(+) clusters, the
      use of a quantum diatomic-in-molecules Hamiltonian constructed from recent ab
      initio calculations reveals some possible inadequacies of the 1/r(4) ion/dipole
      interaction at intermediate distances due to some residual charge transfer.

PMID- 16435818
TI  - An ab initio based global potential energy surface describing CH5+ --> CH3+ + H2.
AB  - A full-dimensional, ab initio based potential energy surface (PES) for CH(5)(+),
      which can describe dissociation is reported. The PES is a precise fit to 36173
      coupled-cluster [CCSD(T)] calculations of electronic energies done using an aug
      cc-pVTZ basis. The fit uses a polynomial basis that is invariant with respect to
      permutation of the five H atoms, and thus describes all 120 equivalent minima.
      The rms fitting error is 78.1 cm(-1) for the entire data set of energies up to
      30,000 cm(-1) and a normal-mode analysis of CH(5)(+) also verifies the accuracy
      of the fit. Two saddle points have been located on the surface as well and
      compared with previous theoretical work. The PES dissociates correctly to the
      fragments CH(3)(+) + H(2) and the equilibrium geometry and normal-mode analyses
      of these fragments are also presented. Diffusion Monte Carlo calculations are
      done for the zero-point energies of CH(5)(+) (and some isotopologs) as well as
      for the separated fragments of CH(5)(+), CH(3)(+) + H(2) and those of CH(4)D(+),
      CH(3)(+) + HD and CH(2)D(+) + H(2). Values of D(0) are reported for these
      dissociations. A molecular dynamics calculation of CH(4)D(+) dissociation at one
      total energy is also performed to both validate the applicability of the PES for
      dynamics studies as well as to test a simple classical statistical prediction of
      the branching ratio of the dissociation products.

PMID- 16435819
TI  - Thermochemistry of the fluoroformyloxyl radical: a computational study based on
      coupled cluster theory.
AB  - The standard enthalpy of formation of FCO(2) (X (2)B(2)) was determined by a
      computational approach based on coupled cluster theory [CCSD(T)] with energies
      extrapolated to the basis-set limit, with additional corrections accounting for
      core-valence correlation, scalar relativity, spin-orbit coupling, and zero-point
      vibrational motions. Utilizing a variety of independent reaction schemes, our
      best estimate is Delta(f)H(o)(0)(FCO(2)) = -86.0 +/- 0.6 kcal mol(-1)
      [Delta(f)H(o)(298) )(FCO(2)) = -86.7 +/- 0.6 kcal mol(-1)], which is shown to be
      more accurate than previous theoretical and experimental values. The chosen
      computational procedure was also applied to HCO (X (2)A'), where we find
      excellent agreement with experiment, and to FCO (X (2)A'), where we recommend an
      improved value of Delta(f)H(o)(0)(FCO) = -42.1 +/- 0.5 kcal mol(-1) [
      Delta(f)H(o)(298)(FCO) = -42.0 +/- 0.5 kcal mol(-1)]. Further theoretical results
      concern the C-F bond dissociation energy, electron affinity, ionization energy,
      first and second excitation energies in FCO(2), fluoride ion affinity of CO(2),
      and equilibrium geometries of the molecules treated presently. For FCO (X (2)A')
      we propose an improved equilibrium structure: r(e)(CF) = 132.5(2) pm, r(e)(CO) =
      116.7(2) pm, and theta(e)(FCO) = 127.8(2)(o).

PMID- 16435820
TI  - Adiabatic passage by light-induced potentials in polyatomic molecules.
AB  - In this paper we study the first application of adiabatic passage by light
      induced potentials in polyatomic molecules. We analyze the effects of increasing
      the dimensionality of the system on the adiabatic requirements of the method and
      the role of intramolecular coupling among the vibrational modes. By using a model
      of two-dimensional displaced harmonic oscillators with or without rotation of the
      normal mode axis of the excited states (Duschinsky effect) we find that (1) it is
      possible to selectively transfer the vibrational population by adiabatic
      elongation of the bonds, (2) the adiabatic demands depend mainly on the energy
      barrier between the ground and excited electronic configurations, and not on the
      dimension of the system, (3) in the presence of intramolecular couplings the
      selective transfer can be achieved but at the cost of increasing the duration
      and/or the intensity of the pulses, which are needed to overcome small avoided
      crossings, and (4) the problem of selectivity becomes more important as the
      vibrational energy of the initial wave function increases.

PMID- 16435821
TI  - Thermal lens spectroscopy in liquid argon solutions: (Deltav = 6) C-H vibrational
      overtone absorption of methane.
AB  - A dual-beam thermal lens technique has been used to obtain the absorption
      spectrum of the (Deltav = 6) C-H stretch of liquid methane and methane in liquid
      argon solutions. The lowest concentration detected was 1 x 10(-3) (mole fraction)
      of CH(4) in liquid Ar with a continuous wave laser power of 20 mW. The thermal
      lens signal is linear with the mole fraction of methane up to 1 x 10(-2) but not
      for higher concentrations. Considering the system CH(4)-Ar as an ideal solution,
      the factors that contribute to the thermal lens signal were calculated as a
      function of the concentration of methane. A mechanism of energy transfer based on
      the gas-phase results could explain qualitatively the dependence of the magnitude
      of the signal on the mole fraction of methane.

PMID- 16435823
TI  - Dynamical study of H2 and D2 desorbing from a Cu(111) surface.
AB  - A theoretical study of H(2) and D(2) desorbing from Cu(111) is reported. The
      study makes use of the LEPS PES of Dai and Zhang [J. Chem. Phys. 1995, 102,
      6280]. The LEPS parameters have been modified in order to lower the barrier
      threshold in conformity with accurate ab initio electronic structure
      calculations. The topological study of the modified PES by the CHAIN method
      reveals unambiguously that the transition state (TS) is located at the top of a
      unique early barrier along the desorption path. The adsorbed H atoms are supposed
      to be in thermal equilibrium with the metal surface. Batches of classical
      trajectories (CT) are then carried out from the TS onto the products with their
      initial conditions canonically distributed and the effect of their possible
      recrossing of the TS taken into account according to Keck's method [Discuss.
      Faraday Soc. 1962, 33, 173]. Product state distributions are then calculated
      using the Gaussian weighting procedure [Chem. Phys. Lett. 2004, 397, 106] to
      account for the quantization of the vibration motion of the desorbed diatom.
      These distributions are in overall good agreement with experimental measurements.
      On average, the early barrier to desorption results in a significant vibrational
      excitation of the final diatom and a strong deexcitation of its rotational
      angular momentum J from the TS onto the products. Moreover, the orientation of
      the rotation plane is roughly random for low values of J (both cartwheel and
      helicopter motions are observed) while it is more likely parallel to the metal
      surface for large values of J (predominance for helicopter motion). These
      findings are analyzed in some details.

PMID- 16435822
TI  - Isoelectronic homologues and isomers: tropolone, 5-azatropolone, 1-H-azepine-4,5
      dione, saddle points, and ions.
AB  - Computational studies of 12 64-electron homologues and isomers of tropolone in
      the S(0) electronic ground state are reported. Three minimum-energy structures,
      tropolone (Tp), 5-azatropolone (5Azt), and 5-H-5-azatropolonium (5AztH(+)), have
      an internal H-bond and planar C(s)) geometry, and three, tropolonate (TpO(-)), 5
      azatropolonate (5AzO(-)), and 1-H-azepine-4,5-dione (45Di), lack the H-bond and
      have twisted C(2) geometry. All 6 substances have an equal double-minimum
      potential energy surface and a saddle point with planar C(2)(v) geometry. The
      energy for the gas-phase isomerization reaction 45Di --> 5Azt is near +4 kJ mol(
      1) at the MP4(SDQ)/6-311++G(df,pd)//MP2/6-311++G(df,pd) (energy//geometry)
      theoretical level and around -20 kJ mol(-1) at lower theoretical levels. The
      dipole moments computed for 45Di and 5Azt are 9.6 and 2.1 D, respectively, and
      this large difference contributes to MO-computed free energies of solvation that
      strongly favor--as experimentally observed--45Di over 5Azt in chloroform solvent.
      The MO-computed energy for the gas-phase protonation reaction 45Di + H(+) -->
      5AztH(+) is -956.4 kJ mol(-1), leading to 926.8 kJ mol(-1) as the estimated
      proton affinity for 45Di at 298 K and 1 atm. The intramolecular dynamical
      properties predicted for 5Azt and 5AztH(+) parallel those observed for tropolone.
      They are therefore expected to exhibit spectral tunneling doublets. Once they are
      synthesized, they should contribute importantly to the understanding of
      multidimensional intramolecular H transfer and dynamical coupling processes.

PMID- 16435824
TI  - Morphology of polythiophene and polyphenyl films produced via surface
      polymerization by ion-assisted deposition.
AB  - Conducting polymer films are grown by either mass-selected or non-mass-selected,
      hyperthermal thiophene ions coincident on a surface with a thermal beam of
      organic monomers of either alpha-terthiophene (3T) or p-terphenyl (3P) neutrals.
      Previous experiments verified polymerization of both 3T and 3P by 200 eV
      C(4)H(4)S(+) during surface polymerization by ion-assisted deposition (SPIAD). A
      wide variety of structures are observed by scanning electron microscopy to form
      in the SPIAD polythiophene and polyphenyl films. These structures include
      microscale islands, lamellar structures, fractal-like growth patterns, and
      nanoscale crystallites. Some of the deposited films diffract X-rays while others
      show electron micrographs of crystallites. The variation of these patterns with
      deposition conditions clearly indicate that ion-induced polymerization mediates
      film morphology through control of ion energy and ion/neutral ratio. Furthermore,
      these ion-assisted events mediate important thermal processes such as
      sublimation.

PMID- 16435825
TI  - Unimolecular dissociation of the CH3OCO radical: an intermediate in the CH3O + CO
      reaction.
AB  - This work investigates the unimolecular dissociation of the methoxycarbonyl,
      CH(3)OCO, radical. Photolysis of methyl chloroformate at 193 nm produces nascent
      CH(3)OCO radicals with a distribution of internal energies, determined by the
      velocities of the momentum-matched Cl atoms, that spans the theoretically
      predicted barriers to the CH(3)O + CO and CH(3) + CO(2) product channels. Both
      electronic ground- and excited-state radicals undergo competitive dissociation to
      both product channels. The experimental product branching to CH(3) + CO(2) from
      the ground-state radical, about 70%, is orders of magnitude larger than Rice
      Ramsperger-Kassel-Marcus (RRKM)-predicted branching, suggesting that previously
      calculated barriers to the CH(3)OCO --> CH(3) + CO(2) reaction are dramatically
      in error. Our electronic structure calculations reveal that the cis conformer of
      the transition state leading to the CH(3) + CO(2) product channel has a much
      lower barrier than the trans transition state. RRKM calculations using this cis
      transition state give product branching in agreement with the experimental
      branching. The data also suggest that our experiments produce a low-lying excited
      state of the CH(3)OCO radical and give an upper limit to its adiabatic excitation
      energy of 55 kcal/mol.

PMID- 16435826
TI  - Dynamics of swelling/contracting hard spheres surmised by an irreversible
      Langevin equation.
AB  - The diffusion of molecules through uniform homogeneous materials can readily be
      described by Brownian motion or generalizations thereof. The further
      generalization of these models to describe molecular diffusion through
      heterogeneous and nonstationary solvents is much less understood.
      Phenomenological nonstationary generalizations of the generalized Langevin
      equation (GLE) have earlier been developed satisfying the fluctuation-dissipation
      relationship in quasi-equilibrium limits while exhibiting somewhat complex
      behavior away from equilibrium. This reduced-dimensional representation should be
      capable of describing the diffusion of a particle through a colloidal suspension
      whose average particle size is tuned by an external driving force such as pH. A
      simple particle model of such a process involves the motion of a hard-sphere
      particle in an explicit environment of swelling hard spheres. The velocity
      autocorrelation functions observed in a large number of simulations of the
      particle model under various swelling rates agree precisely with those of a
      single form of the nonstationary phenomenological model. Though this procedure is
      not an explicit projection of the mechanical system onto the nonstationary GLE,
      it does show that the latter correctly describes the dynamics of the projected
      coordinate--namely, diffusion of the solute--under nonequilibrium conditions.
      Both nonequilibrium solvent models lead to behavior reminiscent of beta
      relaxation processes at packing fractions substantially below that of the glass
      transition.

PMID- 16435827
TI  - Dynamics of HCl collisions with hydroxyl- and methyl-terminated self-assembled
      monolayers.
AB  - Molecular beam scattering techniques are used to explore the energy exchange and
      thermal accommodation efficiencies of HCl in collisions with long-chain OH- and
      CH(3)-terminated self-assembled monolayers (SAMs) on gold. Upon colliding with
      the nonpolar methyl-terminated SAM, HCl (E(i) = 85 kJ/mol) is found to transfer
      the majority, 83%, of its translational energy to the surface. The extensive
      energy loss for HCl helps to bring the molecules into thermal equilibrium with
      the monolayer. Specifically, 72% of the HCl approaches thermal equilibrium prior
      to desorption. For the molecules that do not thermally accommodate, but scatter
      after an impulsive collision with the surface, the final translational energy is
      observed to be directly proportional to the surface temperature as the thermal
      surface energy and gas translational energy exchange during the collision. For
      the OH-terminated SAM, the impulsively scattered HCl escapes from the surface
      with slightly more average energy. The rigid nature of the OH-terminated SAM is
      due to the extended intra-monolayer hydrogen-bonding network that restricts some
      of the low-energy modes of the surface. However, despite the rigid nature of this
      system, the extent of thermal accommodation for HCl on these two surfaces is
      remarkably similar. It appears that the potential energy well between the
      impinging HCl and the polar surface groups is sufficient enough to trap HCl
      molecules that would otherwise scatter impulsively from this rigid SAM.

PMID- 16435828
TI  - Doubly protonated benzene in the gas phase.
AB  - Structural aspects and the unimolecular fragmentations of doubly protonated
      benzene are studied by means of tandem-mass spectrometry. The corresponding
      dications are generated by electron ionization (EI) of 1,3- and 1,4
      cyclohexadienes, respectively. It is suggested that EI of 1,3-cyclohexadiene
      leads to the singlet state of doubly protonated benzene, whereas EI of 1,4
      cyclohexadiene yields a mixture of singlet and triplet states. Unimolecular
      fragmentation of doubly protonated benzene exclusively proceeds via
      dehydrogenation leading to the benzene dication. The proton affinities (PAs) of
      protonated benzene amount to PA(C(6)H(7)(+))(meta) = 1.9 +/- 0.3 eV for
      protonation taking place at the meta-position, PA(C(6)H(7)(+))(ortho) = 1.5 +/-
      0.2 eV, and PA(C(6)H(7)(+))(para) = 0.9 +/- 0.2 eV, respectively. Various facets
      of the experiments are compared with density functional theory calculations and
      generally good agreement is found.

PMID- 16435829
TI  - On the statistical nature of collision and surface-induced dissociation: a
      theoretical investigation of aluminum clusters.
AB  - The unimolecular dissociation dynamics of aluminum clusters following collision
      with either a rare gas atom or a surface is investigated by classical trajectory
      simulations with model potentials. Two conformers of Al(6) with very distinct
      shapes, i.e., the spherical O(h) and planar C(2)(h) clusters, are considered in
      this work. The initial vibrational energy and angular momentum distributions
      resulting from collision, as well as the energy and angular momentum resolved
      lifetime distributions, of excited clusters were determined for both collision
      induced dissociation (CID) and surface-induced dissociation (SID) processes. The
      partitioning of excitation energy acquired upon collision was found to depend on
      the excitation mechanism (CID or SID), as well as on the cluster molecular shape,
      especially in the case of CID. For both types of processes, the energy and
      angular momentum resolved excited cluster lifetime distributions were found to
      decay exponentially, in agreement with statistical theories of chemical
      reactions, suggesting intrinsic Rice-Ramsperger-Kassel-Marcus (RRKM) behavior.
      Moreover, the simulated microcanonical rate constants determined from the cluster
      lifetime distributions are in good agreement with the predictions of the orbiting
      transition state model of phase space theory (OTS/PST), which further supports
      the statistical character of cluster CID and SID. Thus, in the CID and SID of
      highly fluxional systems such as aluminum clusters, the rate of intramolecular
      vibrational energy redistribution (IVR) is much faster than the dissociation
      rate, which validates one of the key assumptions, i.e., post-collision
      statistical behavior, underlying the models that are routinely used to determine
      cluster binding energies from experimental CID/SID cross sections.

PMID- 16435830
TI  - A quantum wave packet dynamics study of the N(2D) + H2 reaction.
AB  - We report a dynamics study of the reaction N((2)D) + H(2) (v=0, j=0-5) --> NH + H
      using the time-dependent quantum wave packet method and a recently reported
      single-sheeted double many-body expansion potential energy surface for
      NH(2)(1(2)A' ') which has been modeled from accurate ab initio multireference
      configuration-interaction calculations. The calculated probabilities for (v=0,
      j=0-5) are shown to display resonance structures, a feature also visible to some
      extent in the calculated total cross sections for (v=0, j=0). A comparison
      between the calculated centrifugal-sudden and coupled-channel reaction
      probabilities validate the former approximation for the title system. Rate
      constants calculated using a uniform J-shifting scheme and averaged over a
      Boltzmann distribution of rotational states are shown to be in good agreement
      with the available experimental values. Comparisons with other theoretical
      results are also made.

PMID- 16435831
TI  - Ab initio kinetics for the unimolecular reaction C6H5OH --> CO + C5H6.
AB  - The unimolecular decomposition of C(6)H(5)OH on its singlet-state potential
      energy surface has been studied at the G2M//B3LYP/6-311G(d,p) level of theory.
      The result shows that the most favorable reaction channel involves the
      isomerization and decomposition of phenol via 2,4-cyclohexadienone and other low
      lying isomers prior to the fragmentation process, producing cyclo-C(5)H(6) + CO
      as major products, supporting the earlier assumption of the important role of the
      2,4-cyclohexadienone intermediate. The rate constant predicted by the
      microcanonical RRKM theory in the temperature range 800-2000 K at 1 Torr--100 atm
      of Ar pressure for CO production agrees very well with available experimental
      data in the temperature range studied. The rate constants for the production of
      CO and the H atom by O-H dissociation at atmospheric Ar pressure can be
      represented by k(CO) = 8.62 x 10(15) T(-0.61) exp(-37,300/T) s(-1) and k(H) =
      1.01 x 10(71) T(-15.92) exp(-62,800/T) s(-1). The latter process is strongly P
      dependent above 1000 K; its high- and low-pressure limits are given.

PMID- 16435832
TI  - Soft-landing of peptides onto self-assembled monolayer surfaces.
AB  - Mass-selected peptide ions produced by electrospray ionization were deposited as
      ions by soft-landing (SL) onto fluorinated and hydrogenated self-assembled
      monolayer (FSAM and HSAM) surfaces using a Fourier transform ion cyclotron
      resonance mass spectrometer (FT-ICR MS) specially designed for studying
      collisions of large ions with surfaces. Analysis of modified surfaces was
      performed in situ by combining 2 keV Cs(+) secondary ion mass spectrometry with
      FT-ICR detection of the sputtered ions (FT-ICR-SIMS). Similar SIMS spectra
      obtained following SL at different collision energies indicate that peptide
      fragmentation occurred in the analysis step (SIMS) rather than during ion
      deposition. The effect of the surface on SL was studied by comparing the
      efficiencies of SL on gold, FSAM, HSAM, and COOH-terminated SAM surfaces. It was
      found that FSAM surfaces are more efficient in retaining ions than their HSAM
      analogues, consistent with their larger polarizability. The efficiency of soft
      landing of different peptides on the FSAM surface increases with the charge state
      of the ion, also consistent with an ion-polarizable molecule model for the
      initial stage of soft-landing on SAM surfaces. The gradual decrease of peptide
      ion deposition efficiency with an increase in collision energy found
      experimentally was quantitatively rationalized using the hard-cube model.

PMID- 16435833
TI  - First optically active molecular electronic wires.
AB  - [structure: see text]. The optically active molecular electronic wires (S)- and
      (R)-7 containing an oligo-arylene-ethynylene structure and a chiral 1,1'
      binaphthyl unit are synthesized. These molecules are incorporated into nanowell
      devices by self-assembly on the gold surface. In the nanowell devices, the median
      currents from the molecules containing both S and R enantiomers are significantly
      smaller than those from the pure S or R molecule. Compounds (R)- and (S)-7 are
      also less conductive than the fully conjugated oligo-phenylene-ethynylene-thiol
      molecules.

PMID- 16435834
TI  - 1,3-indane-based chromogenic calixpyrroles with push-pull chromophores: synthesis
      and anion sensing.
AB  - [structure: see text]. Knoevenagel condensation of 2-formyl
      octamethylcalix[4]pyrrole with selected 1,3-indanedione derivatives yields
      calix[4]pyrrole anion sensors with push-pull chromophores displaying strong
      intramolecular charge transfer. The push-pull feature results in augmented signal
      output as well as in dramatic changes in anion selectivity exemplified by a 50
      fold increase in acetate vs chloride selectivity compared to the parent
      calix[4]pyrrole.

PMID- 16435835
TI  - Rhodium-Catalyzed Asymmetric Conjugate Additions of Boronic Acids to enones using
      DIPHONANE: a novel chiral bisphosphine ligand.
AB  - [reaction: see text] The synthesis of a novel enantiopure C2-symmetric
      bisphosphine, DIPHONANE, was accomplished starting from 2,5-norbornadione,
      utilizing (R,R)- and/or (S,S)-(2,3-O-di[(phenylamino)carbonyl]tartaric acid for
      the resolution of an intermediate phosphineoxide. The application of this ligand
      in the rhodium-catalyzed asymmetric conjugate addition of boronic acids to cyclic
      enones provides the 1,4-addition products in good yields (69-98%) and high ee's
      (78-95% ee). A byproduct arising from a consecutive 1,4-addition and 1,2-addition
      was also observed.

PMID- 16435836
TI  - A new approach to difficult Fischer synthesis: the use of zinc chloride catalyst
      in triethylene glycol under controlled microwave irradiation.
AB  - [reaction: see text]. Application of triethylene glycol with catalytic quantity
      of zinc chloride (ZnCl2/TEG) is described as a new and efficient reaction medium
      for a difficult Fischer synthesis, leading to sensitive indoles. Transformation
      of the 3-acetyl-1-methylthiocycloalka[c]pyridine phenylhydrazones and p
      methoxyphenylhydrazones into the 2-(2-pyridyl)indoles and 5-methoxy-2-(2
      pyridyl)indoles, which are the synthons in our total synthesis of the
      sempervirine-type alkaloids, is carried out under controlled microwave
      irradiation in dry zinc chloride solution (0.16 M) in TEG. This protocol produces
      indoles from acetophenone or cyclohexanone via their phenylhydrazones in
      excellent yields.

PMID- 16435837
TI  - Hg2+-selective OFF-ON and Cu2+-selective ON-OFF type fluoroionophore based upon
      cyclam.
AB  - [structure: see text]. A new cyclam derivative having two different fluorophores
      of pyrene and NBD subunits was prepared, and its Hg2+- and Cu2+-selective
      signaling behaviors were investigated. The detection limits for the analysis of
      Hg2+ and Cu2+ ions were found to be 7.9 x 10(-6) and 2.6 x 10(-7) M in aqueous
      acetonitrile solution (H2O-CH3CN = 10:90, v/v), respectively. The compound also
      exhibited a selective Hg2+/Cu2+-induced OFF-ON-OFF type of signaling pattern that
      can be utilized for the construction of functional supramolecular switching
      systems.

PMID- 16435838
TI  - Practical preparation method of polymer-incarcerated (PI) palladium catalysts
      using Pd(II) salts.
AB  - [reaction: see text]. Polymer-incarcerated (PI) palladium catalyst was
      practically prepared from inexpensive Pd(II) salts and a polystyrene-based
      copolymer under reducing conditions. Remarkable effects of alkali metal salts on
      the palladium loading were observed. PI Pd thus prepared showed high catalytic
      activity in Mizoroki-Heck reactions and Suzuki-Miyaura couplings with a range of
      substrates including an aryl chloride. In all cases, the Pd catalyst was
      recovered quantitatively without leaching, and reused several times without
      significant loss of activity.

PMID- 16435839
TI  - [3+2] cross-coupling reactions of aziridines with isocyanates catalyzed by
      nickel(II) iodide.
AB  - [reaction: see text]. Cycloaddition of aziridines with isocyanates proceeded
      smoothly in the presence of a nickel catalyst, and five iminooxazolidine
      derivatives were isolated in good yields. The best result was obtained when the
      reaction was carried out in the presence of NiI2, and a longer reaction time
      allowed the isomerization of the iminooxazolidine to the corresponding
      imidazolidinone derivatives.

PMID- 16435840
TI  - Synthesis of 3,6-diaminophthalimides for ureidophthalimide-based foldamers.
AB  - [reaction: see text]. Herein, we report an improved methodology for the synthesis
      of a variety of 3,6-diaminophthalimides in high yields. This enables decoration
      of the periphery of foldamers with a wide range of functionalities.

PMID- 16435841
TI  - New fluorescent amide-functionalized phenylethynylthiophene low molecular weight
      gelator.
AB  - [reaction: see text]. An amide-functionalized phenylethynylthiophene gelator has
      been synthesized. Self-assembly of this molecule via cooperative hydrogen bonding
      and pi-stacking induced gelation of a variety of organic solvents. The presence
      of aggregates was confirmed by concentration-dependent absorption and
      fluorescence properties. SEM and TEM studies reveal the formation of fiberlike
      nanostructure.

PMID- 16435842
TI  - Bronsted guanidine acid-base ionic liquids: novel reaction media for the
      palladium-catalyzed Heck reaction.
AB  - [reaction: see text]. Bronsted acid-base ionic liquids (GILs) based on guanidine
      and acetic acid are efficient reaction media for palladium-catalyzed Heck
      reactions. They offer the advantages of high activity and reusability. GIL2 plays
      multiple roles in the reaction: it could act as solvent, as a strong base to
      facilitate beta-hydride elimination, and as a ligand to stabilize activated Pd
      species.

PMID- 16435843
TI  - A highly regioselective amination of 6-aryl-2,4-dichloropyrimidine.
AB  - [reaction: see text]. A highly regioselective amination of 6-aryl-2,4
      dichloropyrimidine with aliphatic secondary amines and aromatic amines has been
      developed which strongly favors the formation of the C4-substituted product. The
      reactions with aliphatic amines are carried out using LiHMDS as the base and are
      catalyzed by Pd, while the aromatic amines require no catalyst.

PMID- 16435844
TI  - Adaptive dendron: a bile acid oligomer behaving as both normal and inverse
      micellar mimic.
AB  - [reaction: see text]. The normal and inverse micellar property of a bile-acid
      based dendritic structure was established through dye solubilization studies in
      both polar and nonpolar media.

PMID- 16435845
TI  - Electrolysis as an efficient key step in the homogeneous polymer-supported
      synthesis of N-substituted pyrroles.
AB  - [reaction: see text]. An efficient and general route to the soluble polymer
      assisted synthesis of a set of 14 different N-substituted pyrroles using
      dendritic polyglycerol as a high-loading support is presented. The transformation
      of furan to the key intermediate 2,5-dialkoxytetrahydrofuran was performed by
      electrochemical oxidation followed by catalytic hydrogenation with Pt/C in high
      yield. Both reactions required heterogeneous reagents which can be conveniently
      used with polyglycerol as a soluble support.

PMID- 16435846
TI  - Phosphonation of arenes with dialkyl phosphites catalyzed by Mn(II)/Co(II)/O2
      redox couple.
AB  - [reaction: see text]. Arylphosphonates were first synthesized through a catalytic
      phosphonation of various arenes with dialkyl phosphites under the influence of an
      Mn(OAc)2/Co(OAc)2/O2 redox couple. For instance, the reaction of benzene with
      diethyl phosphite in the presence of Mn(OAc)2 (5 mol %) and Co(OAc)2 (1 mol %)
      under a mixed gas of O2 (0.5 atm) and N2 (0.5 atm) at 45 degrees C led to diethyl
      phenylphosphonate in 81% selectivity at 62% conversion. This is the first
      successful phosphonation of benzene with dialkyl phosphites through a catalytic
      radical process.

PMID- 16435847
TI  - Construction of electrocatalytic electrodes bearing the triphenylamine nucleus
      covalently bound to carbon. A halogen dance in protonated aminotriphenylamines.
AB  - [reaction: see text]. The triarylamine nucleus has been attached to a carbon
      fiber electrode by diazotization of an aminotriphenylamine followed by
      electrochemical reduction. The resulting electrodes can electrocatalyze the
      oxidation of organic substrates. In acid, 4-amino-4',4' '-dibromotriphenylamine
      undergoes dismutation into a mixture of amines containing from 0 to 3 bromine
      atoms.

PMID- 16435848
TI  - An improved synthesis of alpha-carbolines under microwave irradiation.
AB  - [reaction: see text]. Alpha-carbolines are interesting core structures for
      designing DNA-interacting small molecules. However, these compounds are not
      commercially available and their synthetic methods are low yielding or time
      consuming. The shortest synthetic route, the modified Graebe-Ullmann reaction,
      has been optimized by using microwave heating in four different types of
      apparatus to give shorter reaction times and enhanced yields. Optimized
      conditions enabled the preparation of a small library of alpha-carbolines.

PMID- 16435849
TI  - A concise total synthesis of naamidine A.
AB  - [reaction: see text]. A total synthesis of naamidine A is reported. Key benefits
      of the described pathway include its brevity, its synthetic ease, and its
      flexibility with respect to the preparation of analogues. Formation of the 2
      aminoimidazole core is achieved by condensation of the appropriate alpha
      aminoketone with cyanamide.

PMID- 16435850
TI  - Studies directed toward the synthesis of terreulactone A: rapid construction of
      the A, B, C rings.
AB  - [structure: see text]. An efficient, rapid synthesis of the A, B, C rings of
      terreulactone A is described. Key steps in the synthesis include a
      diastereoselective benzylic acid rearrangement to create the desired quaternary
      center at C2 and a mild bromolactonization to assemble the lactonic ring A.

PMID- 16435851
TI  - Synthetic studies on amphidinolide B1.
AB  - [structure: see text]. The syntheses of three fragments, 2, 3, and 4, of
      amphidinolide B1 have been accomplished. The 1,3-isomerization of allylic alcohol
      10 was accomplished via rhenium oxo catalysis and has been applied successfully
      in the synthesis. (-)-MIB-catalyzed asymmetric vinylzinc addition to aldehyde 31
      and the regio- and stereoselective epoxidation of unsymmetrical divinyl methanol
      32 were key steps.

PMID- 16435852
TI  - Highly regio- and stereoselective synthesis of tetrasubstituted olefins by the
      three-component tandem reaction of allylzinc bromide, acetylenic sulfone, and
      halohydrocarbon.
AB  - [reation: see text]. Tetrasubstituted olefins containing a 1,4-diene structural
      unit can be regio- and stereoselectively constructed in one pot by the
      allylzincation of acetylenic sulfones, followed by Negishi cross-coupling with
      halohydrocarbons in the presence of catalytic Ni(PPh3)2Cl2.

PMID- 16435853
TI  - [3]Pseudorotaxane-like complexes formed between bipyridinium dications and bis-p
      xylyl[26]crown-6.
AB  - [structure: see text]. The crown ether BPX26C6 forms a [3]pseudorotaxane-like
      complex with the N,N'-dimethyl-4,4'-bipyridinium dication both in solution and in
      the solid state. The facile one-pot synthesis of a [2]rotaxane from neutral
      precursors-BPX26C6, 4,4'-dipyridyl, and 3,5-di-tert-butylbenzyl bromide-suggests
      that BPX26C6 may bind to (mono)pyridinium cations in a [2]pseudorotaxane-like
      manner.

PMID- 16435854
TI  - A putative precursor of isomalabaricane triterpenoids from lanosterol synthase
      mutants.
AB  - [reaction: see text]. Known lanosterol synthase mutants produce monocyclic or
      tetracyclic byproducts from oxidosqualene. We describe Erg7 Tyr510 mutants that
      cause partial substrate misfolding and generate a tricyclic byproduct. This novel
      triterpene, (13alphaH)-isomalabarica-14(27),17E,21-trien-3beta-ol, is the likely
      biosynthetic precursor of isomalabaricane triterpenoids in sponges. The results
      suggest the facile evolution of protective triterpenoids in sessile animals.

PMID- 16435856
TI  - Mercuric triflate-catalyzed reaction of propargyl acetates with water leading
      vinyl ketones.
AB  - [reaction: see text]. Reaction of propargyl acetate with water catalyzed by
      Hg(OTf)2 afforded vinyl ketone as the major product along with a dimeric vinyl
      mercuric product and normal hydration products in small amounts. The reaction is
      an alternative to the Meyer-Schuster and Rupe rearrangement applicable to primary
      alcohols, although the mechanism is entirely different.

PMID- 16435855
TI  - Resolution of methyl nonactate by Rhodococcus erythropolis under aerobic and
      anaerobic conditions.
AB  - [reaction: see text]. An efficient resolution of methyl nonactate is reported by
      biotransformation in shake flask cultures of Rhodococcus erythropolis. The
      equilibrium of the reaction redox system can be manipulated by switching from
      aerobic to anaerobic growth, thereby generating both enantiomers of the target in
      excellent yield and enantiomeric purity.

PMID- 16435857
TI  - Low-temperature n-butyllithium-induced rearrangement of allyl 1,1-dichlorovinyl
      ethers.
AB  - [reaction: see text]. Upon treatment with n-BuLi at low temperatures, a variety
      of allyl 1,1-dichlorovinyl ethers 2 undergo rearrangement to furnish gamma,delta
      unsaturated esters 3 after alcohol addition. Compounds containing quaternary
      centers (3e: R1 = H, R2, R3 = -(CH2)5-; 3f: R1 = H, R2 = CH3, R3 =
      (CH2)2CH(CH3)2) may be formed in high yield and under mild conditions utilizing
      this protocol. The reaction is stereospecific and may be applied to the
      preparation of Delta(2,3)-beta-C-glycosides and alpha,beta-disubstituted
      lactones.

PMID- 16435858
TI  - Mechanistic implications of nickel-catalyzed reductive coupling of aldehydes and
      chiral 1,6-enynes.
AB  - [reaction: see text]. A study of nickel-catalyzed reductive coupling reactions of
      aldehydes and chiral 1,6-enynes has provided evidence for three distinct
      mechanistic pathways that govern regioselectivity in this transformation. In the
      absence of a phosphine additive, high regioselectivity and high
      diastereoselectivity are obtained as a direct result of coordination of both the
      alkyne and the olefin to the metal center during the C-C bond-forming step.

PMID- 16435859
TI  - Ring-opening/ring-closing metathesis (RORCM) reactions of 7-Azanorbornene
      derivatives. An entry into perhydroindolines.
AB  - [reaction: see text]. 7-Azanorbornenes undergo ring-opening/ring-closing
      metathesis upon treatment with the second-generation Grubbs catalyst to give
      hexahydroindoline derivatives.

PMID- 16435860
TI  - Utilization of a 1,2-dioxine for the synthesis of the four possible stereoisomers
      of oak lactone.
AB  - [reaction: see text]. The natural products cis- and trans-oak lactone (1) have
      been prepared, along with their enantiomeric counterparts, from furanone 12,
      which was itself prepared from racemic 1,2-dioxine 9 and a chiral malonate
      diester. The key steps in the synthesis of 1 are the use of the malonate diester
      as a chromatographic resolving agent and the decarboxylation of 13, which can be
      directed to give either the cis- or trans-product. This leads to all four
      possible oak lactone stereoisomers from a common intermediate.

PMID- 16435861
TI  - Cysteine-derived s-protected oxazolidinones: potential chemical devices for the
      preparation of peptide thioesters.
AB  - [reaction: see text]. An N-S acyl-transfer-mediated preparation of peptide
      thioesters using the S-protected oxazolidinone derived from cysteine has been
      developed and applied to the synthesis of a 32-mer biologically active peptide by
      native chemical ligation protocols.

PMID- 16435862
TI  - Synthesis of new amphiphilic dendrons bearing aliphatic hydrocarbon surface
      sectors and a monocarboxylic or dicarboxylic acid focal point.
AB  - [structure: see text]. A new series of amphiphilic G1-G3 dendrons containing
      purely aliphatic hydrocarbon dendritic surface sectors and one or two carboxylic
      acid group(s) at the focal point was synthesized in good yields. The key
      branching steps involve diallylation reactions of diethyl malonate or Meldrum's
      acid. These dendrons are highly soluble in hexane despite having highly polar
      carboxylic acid groups at the focal point.

PMID- 16435863
TI  - Total synthesis of (+)-lasonolide A.
AB  - [structure: see text]. An enantiocontrolled total synthesis of (+)-lasonolide A
      has been accomplished by using the sequential cross metathesis and
      macrolactonization for the key assembly of the 20-membered polyene macrolide core
      of the natural product.

PMID- 16435864
TI  - Highly regioselective synthesis of gem-difluoroallenes through magnesium
      organocuprate SN2' substitution.
AB  - [reaction: see text]. The reaction of gem-difluoropropargyl electrophiles with
      Grignard reagents is complicated by the inherent difficulty of executing
      nucleophilic substitutions on a CF2 group, and the facile formation of carbenoid
      intermediates arising from alpha-elimination of fluoride. In the presence of an
      excess amount of a copper salt, a Grignard reagent reacts with gem
      difluoropropargyl bromide via an S(N)2' mechanism to produce gem-difluoroallene
      in high yield. If desired, the resulting difluoroallene can undergo a second
      nucleophilic attack on the CF2 terminus to yield a trisubstituted
      monofluoroallene through an addition-elimination mechanism.

PMID- 16435865
TI  - Nickel-catalyzed reactions of silacyclobutanes with aldehydes: ring opening and
      ring expansion reaction.
AB  - [reaction: see text]. The nickel-catalyzed ring opening reaction of
      silacyclobutanes with aldehydes affords the corresponding alkoxyallylsilanes. In
      contrast, the ring expansion reaction of benzosilacyclobutene with aldehydes
      occurs under nickel catalysis to give oxasilacyclohexenes.

PMID- 16435866
TI  - Microwave-enhanced synthesis of new (-)-steganacin and (-)-steganone aza
      analogues.
AB  - [reaction: see text]. A novel, microwave-enhanced, highly efficient protocol for
      the synthesis of hitherto unknown (-)-steganacin and (-)-steganone 7-aza
      analogues containing a 1,2,3-triazole ring has been presented. Microwave
      irradiation was found to be highly beneficial in promoting the Suzuki reaction
      and the 1,3-dipolar cycloaddition reaction to generate the highly strained medium
      sized ring system of the title molecules.

PMID- 16435867
TI  - Synthesis and conformational analysis of new cyclobutane-fused nucleosides.
AB  - [structure: see text]. A stereselective synthesis of 3-oxabicyclo[3.2.0]heptane
      nucleoside analogues, which were designed as conformational mimics of the anti
      HIV agents 2',3'-didehydro-2',3'-dideoxythimidine (stavudine, d4T) and 2',3'
      didehydro-2',3'-dideoxyadenosine (d4A), is described. The target compounds were
      prepared by condensation of a common intermediate bicyclic acetate, derived from
      a homochiral 2(5H)-furanone, with pyrimidine and purine bases under modified
      Vorbruggen conditions. The conformational behavior of the synthesized nucleoside
      analogues was studied by NMR spectroscopy and X-ray crystallography.

PMID- 16435868
TI  - Highly sensitive sensory materials for fluoride ions based on the dithieno[3,2
      b:2',3'-d]phosphole system.
AB  - [structure: see text]. The newly developed functionalization of an unsubstituted
      dithieno[3,2-b:2',3'-d]phosphole at the 5,5'-positions gives access to
      bis(pinacoleboryl) species that can be utilized as sensory materials for fluoride
      ions. The fluoride-triggered response of the air- and moisture-stable boryl
      functionalized dithienophosphole oxide manifests itself in the generation of a
      new fluorescence emission that can be detected at very low analyte concentrations
      (ppm) or even with the naked eye upon irradiation with UV light (366 nm).

PMID- 16435869
TI  - Engineered biosynthesis of plant polyketides: manipulation of chalcone synthase.
AB  - [reaction: see text]. Chalcone synthase (CHS) is a plant-specific type III
      polyketide synthase catalyzing condensation of 4-coumaroyl-CoA with three
      molecules of malonyl-CoA. Surprisingly, it was demonstrated that S338V mutant of
      Scutellaria baicalensis CHS produced octaketides SEK4/SEK4b from eight molecules
      of malonyl-CoA. Further, the octaketides-forming activity was dramatically
      increased in a CHS triple mutant (T197G/G256L/S338T). The functional conversion
      is based on the simple steric modulation of a chemically inert residue lining the
      active-site cavity.

PMID- 16435870
TI  - Synthesis and unexpected reactivity of Si-H functionalized dithieno[3,2-b:2',3'
      d]phospholes.
AB  - [reaction: see text]. Si-H functionalized, blue light-emitting dithieno[3,2
      b:2',3'-d]phospholes are accessible by reaction of an appropriate bithiophene
      precursor with a dichlorophosphane. Subsequent functionalization of the central
      phosphorus center allows for a fine-tuning of the optoelectronic properties of
      the material. Pt-catalyzed reaction of the Si-H functionalities with alkynes
      affords the hydrosilation products including a polymer by reaction with 1,7
      octadiyne. By contrast, the absence of any substrate leads to the exclusive
      formation of a polymer via dehydrogenative homocoupling.

PMID- 16435872
TI  - Synthesis and biological evaluation of tamandarin B analogues.
AB  - [structure: see text]. The synthesis of two tamandarin B analogues in which the
      N,O-Me2Tyr5 unit was replaced by N-Me-phenylalanine (N-MePhe5) and (S)-2
      (methylamino)-3-(naphthalen-2-yl)propanoic acid (N-MeNaphth5) is described. The
      choice of the macrocyclization site was crucial to achieve satisfactory
      macrolactamization. Coupling between norstatine (Nst1) and threonine (Thr6)
      afforded only a 15% yield, while lactamization between proline (Pro4) and the
      aromatic moiety could be achieved in 65% yield.

PMID- 16435871
TI  - N-heterocyclic carbene catalyzed reaction of enals and 1,2-dicarbonyl compounds:
      stereoselective synthesis of spiro gamma-butyrolactones.
AB  - [reaction: see text]. Nucleophilic heterocyclic carbene (NHC) catalyzed
      annulation of enals and cyclic 1,2-dicarbonyl compounds, opening a route to gamma
      spirolactones, has been observed for the first time. The strategy works well with
      isatins, leading to spiroannulated oxindole derivatives. It is conceivable that
      the spiroannulation protocol reported herein will be applicable to the synthesis
      of important natural products that are endowed with a spiro gamma-butyrolactone
      motif, especially oxindoles and norsesquiterpenoids.

PMID- 16435873
TI  - Gold(I)-catalyzed formation of 4-alkylidene-1,3-dioxolan-2-ones from propargylic
      tert-butyl carbonates.
AB  - [reaction: see text]. A study concerning the gold(I)-catalyzed rearrangement of
      propargylic tert-butyl carbonates into 4-alkylidene-1,3-dioxolan-2-ones is
      described. The mild reaction conditions employed allow the efficient synthesis of
      a variety of cyclic carbonates that would be less conveniently obtained using
      reported methods. Variability in the structure of the final product has been
      observed and is significantly dependent on the nature of the substituent attached
      to the alkyne moiety.

PMID- 16435874
TI  - Hydrogen-mediated aldol reductive coupling of vinyl ketones catalyzed by rhodium:
      high syn-selectivity through the effect of tri-2-furylphosphine.
AB  - [reaction: see text]. Catalytic hydrogenation of methyl vinyl ketone (MVK) and
      ethyl vinyl ketone (EVK) in the presence of diverse aldehydes at ambient
      temperature and pressure using tri-2-furylphosphine-ligated rhodium catalysts
      enables formation of aldol products with high levels of syn-diastereoselectivity.
      A progressive increase in diastereoselectivity is observed upon sequential
      replacement of phenyl residues for 2-furyl residues (Ph3P, FurPh2P, Fur2PhP,
      Fur3P). Hydrogen-labile functional groups, including alkynes, alkenes, benzylic
      ethers, and nitroarenes, remain intact under the coupling conditions.

PMID- 16435875
TI  - Novel synthesis of the ortho ester derivative of 4,5-epoxymorphinan.
AB  - [reaction: see text]. A method was found for the novel synthesis of ortho ester
      derivatives that are potentially useful as selective epsilon opioid receptor
      ligands. An unexpected 17-(cyclopropylmethyl)-4,5alpha-epoxy-6alpha-hydroxy-3,7,7
      trimethoxy-8-oxa-6,14-endoethanomorphinan was produced when 17
      (cyclopropylmethyl)-4,5alpha-epoxy-3-methoxy-6alpha,14-dihydroxy-6beta-(1,3
      dithia-2-yl)-morphinan was treated in methanol with trimethyl orthoformate and
      CuO/CuCl2. This ortho ester derivative was then converted to an ester with acid.
      The structure of the ortho ester was determined by 2D NMR (HMBC) and mass
      spectra.

PMID- 16435876
TI  - Stereoselective synthesis of the western hemisphere of salinomycin.
AB  - [structure: see text]. A convergent and module-based strategy for the asymmetric
      synthesis of the western hemisphere (C1-C17 fragment) of salinomycin has been
      devised. This new synthetic approach relies on highly stereoselective C
      glycosidation and aldol processes.

PMID- 16435877
TI  - Total synthesis of apratoxin A.
AB  - [reaction: see text]. We have achieved a total synthesis of apratoxin A in which
      thiazoline formation was accomplished from the moCys containing amide 4 using
      PPh3(O)/Tf2O. Deprotection of the Troc and allyl ester in 17, coupling with
      tripeptide 3, and deprotection of the allyl ester and the Fmoc, followed by
      macrolactamization provided apratoxin A (1).

PMID- 16435878
TI  - Why is the linking C-C bond in tetrahedranyltetrahedrane so short?
AB  - [structure: see text]. The block-localized wave function (BLW) method has been
      employed to probe the origin of the very short linking C-C bond (1.436 A) in
      tetrahedranyltetrahedrane. Computations show that the vicinal hyperconjugative
      interactions between the two tetrahedranyl groups is stronger than the
      conjugation in butadiene, and if there were no hyperconjugation effect, the bond
      distance would be 1.491 A. Thus, both the hybridization mode and hyperconjugative
      interactions contribute to the shortening of the central C-C bond in
      tetrahedranyltetrahedrane.

PMID- 16435879
TI  - A new method for recycling asymmetric catalysts via formation of charge transfer
      complexes.
AB  - [reaction: see text]. A new concept for recycling asymmetric bis(oxazoline)-type
      catalysts is reported. The formation of charge-transfer complexes between the
      chiral ligand and trinitrofluorenone and their subsequent precipitation and reuse
      by addition of new substrate solutions is described. The efficiency of this
      procedure is demonstrated in a Diels-Alder reaction to reach the expected endo
      product as major isomer (up to 97% de and 94% ee): the catalyst was used up to 12
      times without loss of either activity or selectivity.

PMID- 16435880
TI  - Total synthesis of (+/-)-bipinnatin J.
AB  - [reaction: see text]. The total synthesis of (+/-)-bipinnatin J was achieved
      through a concise route that features the use of a silver ion promoted S(N)1-type
      gamma-alkylation of a siloxyfuran and a diastereoselective Cr(II)-mediated
      macrocyclization to provide bipinnatin J (1), wherein the remote furanone
      stereocenter at C10 induced the relative stereochemistry of the two additional
      stereocenters.

PMID- 16435882
TI  - On the correlation between hydrophobicity, liposome binding and cellular uptake
      of porphyrin sensitizers.
AB  - A crucial factor in choosing a porphyrin or analogous photosensitizer for
      photodynamic therapy (PDT) is its ability to incorporate into the cells. For
      hydrophobic compounds that partition passively into the cytoplasmic membrane, a
      partition coefficient between an organic solvent and water, P, is one factor that
      could be used to predict the molecule's ability to diffuse into biomembranes. We
      synthesized several porphyrins, modified with two, three or four meso
      substituents and studied their spectroscopic and photophysical properties. The
      octanol-water partitioning coefficients, log P, were calculated as a parameter
      for hydrophobicity. We found these porphyrins to be very hydrophobic, with log P
      values in the range of 8.9-11.8. These were correlated with the binding constants
      of these porphyrins into liposomes, K(b), as well as to their uptake by cells.
      The correlation between the estimated log P and K(b) is nearly linear but
      negative, indicating, apparently, that there is lesser binding to liposomes with
      increased hydrophobicity. On the other hand, all of the studied porphyrins are
      taken up by cells, but there is no clear correlation between cellular uptake and
      the log P or K(b). Lipinski's pharmacological "rule of 5" predicts poor
      permeation of drugs into cells when log P is greater than five. This may be
      relevant for diffusional binding to liposomes, where aqueous aggregation can
      interfere strongly with cellular uptake. In such extreme conditions, neither
      liposome binding nor other rules seem to predict porphyrin behavior in vitro.

PMID- 16435883
TI  - In vivo monitoring the changes of interstitial pH and FAD/NADH ratio by
      fluorescence spectroscopy in healing skin wounds.
AB  - The aim of our study was to evaluate the changes of interstitial pH and flavin
      adenine dinucleotide (FAD)/reduced nicotinamide adenine dinucleotide (NADH) ratio
      in healing skin wounds using fluorescence spectroscopy in Sprague Dawley rats. In
      the experiment, excisional and incisional models of wound healing were used. The
      florescein as the pH-sensitive probe using excitation spectra (lambda(Em) = 535
      nm) was used for the measurement of pH changes, and synchronous fluorescence
      spectra (Deltalambda = 60 nm) for the monitoring of FAD/NADH ratio changes were
      measured from the surfaces of healing wounds. Increase of interstitial pH and
      FAD/NADH ratio was recorded during the time interval from the 15th to the 65th
      minute after surgery. The decrease of pH between the 48th and the 72nd hour after
      surgery as well as the increase of FAD/NADH ratio between the 72nd and the 96th
      hour of wound healing were recorded. The results indicate that the use of
      fluorescence spectroscopy may be considered as a valuable tool for noninvasive in
      vivo monitoring of selected redox parameters in the early phases of wound
      healing.

PMID- 16435884
TI  - Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta
      signaling and induces reversible diabetes mellitus.
AB  - Identification of signaling pathways that maintain and promote adult pancreatic
      islet functions will accelerate our understanding of organogenesis and improve
      strategies for treating diseases like diabetes mellitus. Previous work has
      implicated transforming growth factor-beta (TGF-beta) signaling as an important
      regulator of pancreatic islet development, but has not established whether this
      signaling pathway is required for essential islet functions in the adult
      pancreas. Here we describe a conditional system for expressing Smad7, a potent
      inhibitor of TGF-beta signaling, to identify distinct roles for this pathway in
      adult and embryonic beta cells. Smad7 expression in Pdx1+ embryonic pancreas
      cells resulted in striking embryonic beta cell hypoplasia and neonatal lethality.
      Conditional expression of Smad7 in adult Pdx1+ cells reduced detectable beta cell
      expression of MafA, menin, and other factors that regulate beta cell function.
      Reduced pancreatic insulin content and hypoinsulinemia produced overt diabetes
      that was fully reversed upon resumption of islet TGF-beta signaling. Thus, our
      studies reveal that TGF-beta signaling is crucial for establishing and
      maintaining defining features of mature pancreatic beta cells.

PMID- 16435886
TI  - Removing the threat of diclofenac to critically endangered Asian vultures.
AB  - Veterinary use of the nonsteroidal anti-inflammatory (NSAID) drug diclofenac in
      South Asia has resulted in the collapse of populations of three vulture species
      of the genus Gyps to the most severe category of global extinction risk. Vultures
      are exposed to diclofenac when scavenging on livestock treated with the drug
      shortly before death. Diclofenac causes kidney damage, increased serum uric acid
      concentrations, visceral gout, and death. Concern about this issue led the Indian
      Government to announce its intention to ban the veterinary use of diclofenac by
      September 2005. Implementation of a ban is still in progress late in 2005, and to
      facilitate this we sought potential alternative NSAIDs by obtaining information
      from captive bird collections worldwide. We found that the NSAID meloxicam had
      been administered to 35 captive Gyps vultures with no apparent ill effects. We
      then undertook a phased programme of safety testing of meloxicam on the African
      white-backed vulture Gyps africanus, which we had previously established to be as
      susceptible to diclofenac poisoning as the endangered Asian Gyps vultures. We
      estimated the likely maximum level of exposure (MLE) of wild vultures and dosed
      birds by gavage (oral administration) with increasing quantities of the drug
      until the likely MLE was exceeded in a sample of 40 G. africanus. Subsequently,
      six G. africanus were fed tissues from cattle which had been treated with a
      higher than standard veterinary course of meloxicam prior to death. In the final
      phase, ten Asian vultures of two of the endangered species (Gyps bengalensis,
      Gyps indicus) were dosed with meloxicam by gavage; five of them at more than the
      likely MLE dosage. All meloxicam-treated birds survived all treatments, and none
      suffered any obvious clinical effects. Serum uric acid concentrations remained
      within the normal limits throughout, and were significantly lower than those from
      birds treated with diclofenac in other studies. We conclude that meloxicam is of
      low toxicity to Gyps vultures and that its use in place of diclofenac would
      reduce vulture mortality substantially in the Indian subcontinent. Meloxicam is
      already available for veterinary use in India.

PMID- 16435885
TI  - Reconstructing an ancestral mammalian immune supercomplex from a marsupial major
      histocompatibility complex.
AB  - The first sequenced marsupial genome promises to reveal unparalleled insights
      into mammalian evolution. We have used the Monodelphis domestica (gray short
      tailed opossum) sequence to construct the first map of a marsupial major
      histocompatibility complex (MHC). The MHC is the most gene-dense region of the
      mammalian genome and is critical to immunity and reproductive success. The
      marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian
      mammals and the minimal essential MHC of birds. Here we show that the opossum MHC
      is gene dense and complex, as in humans, but shares more organizational features
      with non-mammals. The Class I genes have amplified within the Class II region,
      resulting in a unique Class I/II region. We present a model of the organization
      of the MHC in ancestral mammals and its elaboration during mammalian evolution.
      The opossum genome, together with other extant genomes, reveals the existence of
      an ancestral "immune supercomplex" that contained genes of both types of natural
      killer receptors together with antigen processing genes and MHC genes.

PMID- 16435887
TI  - Limits to forecasting precision for outbreaks of directly transmitted diseases.
AB  - BACKGROUND: Early warning systems for outbreaks of infectious diseases are an
      important application of the ecological theory of epidemics. A key variable
      predicted by early warning systems is the final outbreak size. However, for
      directly transmitted diseases, the stochastic contact process by which outbreaks
      develop entails fundamental limits to the precision with which the final size can
      be predicted. METHODS AND FINDINGS: I studied how the expected final outbreak
      size and the coefficient of variation in the final size of outbreaks scale with
      control effectiveness and the rate of infectious contacts in the simple
      stochastic epidemic. As examples, I parameterized this model with data on
      observed ranges for the basic reproductive ratio (R0) of nine directly
      transmitted diseases. I also present results from a new model, the simple
      stochastic epidemic with delayed-onset intervention, in which an initially
      supercritical outbreak (R0 > 1) is brought under control after a delay.
      CONCLUSION: The coefficient of variation of final outbreak size in the
      subcritical case (R0 < 1) will be greater than one for any outbreak in which the
      removal rate is less than approximately 2.41 times the rate of infectious
      contacts, implying that for many transmissible diseases precise forecasts of the
      final outbreak size will be unattainable. In the delayed-onset model, the
      coefficient of variation (CV) was generally large (CV > 1) and increased with the
      delay between the start of the epidemic and intervention, and with the average
      outbreak size. These results suggest that early warning systems for infectious
      diseases should not focus exclusively on predicting outbreak size but should
      consider other characteristics of outbreaks such as the timing of disease
      emergence.

PMID- 16435888
TI  - A 40-year-old woman who developed jaundice during therapy for thyrotoxicosis.

PMID- 16435889
TI  - A pediatric genetic disorder diagnosed in adulthood.

PMID- 16435890
TI  - The "PharmFree" campaign: educating medical students about industry influence.

PMID- 16435891
TI  - Trends in cholera epidemiology.

PMID- 16435892
TI  - Is antiretroviral therapy cost-effective in South Africa?

PMID- 16435893
TI  - Major potential confounder not addressed.

PMID- 16435894
TI  - The protective effect of male circumcision as a faith lift for the troubled
      paradigm of HIV epidemiology in sub-Saharan Africa.

PMID- 16435895
TI  - Estimated protection too conservative.

PMID- 16435896
TI  - On evidence in support of male circumcision in HIV prevention: what next?

PMID- 16435898
TI  - PfHRP2 measures schizogony, not mechanical blockage.

PMID- 16435900
TI  - Rubbery figures?

PMID- 16435901
TI  - Rush to judgment.

PMID- 16435902
TI  - Male circumcision increases risk for females.

PMID- 16435903
TI  - The money issue.

PMID- 16435904
TI  - Male circumcision and HIV in Africa.

PMID- 16435905
TI  - Two groups not on all fours.

PMID- 16435906
TI  - Male circumcision and HIV control in Africa.

PMID- 16435907
TI  - What are the priorities in malaria research?

PMID- 16435910
TI  - Control of neglected tropical diseases: integrated chemotherapy and beyond.

PMID- 16435911
TI  - Ionizing radiation enhances the expression of the nonsteroidal anti-inflammatory
      drug-activated gene (NAG1) by increasing the expression of TP53 in human colon
      cancer cells.
AB  - The induction of apoptosis in cells of human colon cancer cell lines after gamma
      irradiation was investigated to determine whether apoptosis was mediated by TP53
      and the subsequent expression of its downstream target, the NSAID-activated gene
      (NAG1). HCT116 (TP53(+/+)), HCT15 (TP53 mutant) and TP53 null HCT116 (TP53(-/-))
      cells were irradiated with gamma rays, and apoptosis was measured at various
      times after irradiation. In HCT116 TP53(+/+) cells, apoptosis was increased after
      irradiation; the increase was dependent on the time after treatment and the dose
      of gamma rays. However, in HCT15 TP53 mutant cells and HCT116 TP53(-/-) cells,
      there were no remarkable changes in apoptosis. The expression of TP53 protein in
      HCT116 cells was increased after irradiation and was followed by an increase in
      the expression of NAG1 protein. In contrast, the expression of NAG1 protein in
      TP53 mutant cells and TP53(-/-) cells was not increased by the radiation
      treatment, suggesting that NAG1 was required for apoptosis. The expression of
      NAG1 increased apoptosis in HCT116 cells, but radiation treatment did not further
      increase apoptosis. The transfection of a NAG1 siRNA into HCT116 cells suppressed
      radiation-induced apoptosis and inhibited the induction of NAG1 protein without
      altering the expression of TP53. a NAG1 luciferase promoter construct that
      included both of the TP53 binding sites, was activated by radiation in dose
      dependent manner, while the promoters lacking one or both of the TP53 binding
      sites in the NAG1 promoter activity either was less responsive or did not
      respond. The findings reported here indicate that gamma radiation activates the
      TP53 tumor suppressor, which then increases the expression of NAG1. NAG1 mediates
      the induction of apoptosis in human colorectal cells.

PMID- 16435908
TI  - Incorporating a rapid-impact package for neglected tropical diseases with
      programs for HIV/AIDS, tuberculosis, and malaria.

PMID- 16435912
TI  - Increases in 1H-NMR mobile lipids are not always associated with overt apoptosis:
      evidence from MG-63 human osteosarcoma three-dimensional spheroids exposed to a
      low dose (2 Gy) of ionizing radiation.
AB  - The metabolic changes that occur in MG-63 osteosarcoma three-dimensional tumor
      spheroids exposed to 2 Gy of ionizing radiation, a dose that is comparable to
      radiation therapy, were studied using high-resolution proton nuclear magnetic
      resonance ((1)H-NMR) spectroscopy. Specifically, the (1)H-NMR spectra of control
      and exposed MG-63 spheroids were compared. Small spheroids (about 50-80 microm in
      diameter) with no hypoxic center were used. The spectra of whole MG-63 spheroids
      as well as the perchloric acid extracts of these systems were evaluated. Cell
      damage was also examined by lactate dehydrogenase release and changes in cell
      growth. No cell damage was observed, but numerous metabolic changes took place in
      spheroids after exposure to ionizing radiation. In particular, significant
      increases in both CH(2) and CH(3) mobile lipids, considered by many authors as
      markers of apoptosis and also present in MG-63 spheroids undergoing overt
      apoptosis, were observed in spheroids irradiated with 2 Gy. However, the
      chromatin dye Hoechst 33258 and DNA fragmentation assays showed no overt
      apoptosis up to 7 days after irradiation with this low dose. Thus it is evident
      that increases in mobile lipids do not always indicate actual cell death. A
      detailed analysis of the other metabolic changes observed appears to suggest that
      the cell death program was initiated but not completed. In fact, the completely
      different behavior of two important cellular defense mechanisms, reduced
      glutathione and taurine, in spheroids irradiated with 2 Gy and in those
      undergoing overt apoptosis seems to indicate that these systems are protecting
      spheroids from actual cell death. In addition, these data also suggest that (1)H
      NMR can be used to examine the effects of low doses of ionizing radiation in
      spheroids, a cell model of great complexity that closely resembles tumors in
      vivo. The importance of this possibility in relation to reaching the ultimate
      goal of a better evaluation of the outcome of radiotherapy protocols should not
      be ignored.

PMID- 16435913
TI  - Early gene expression profile in mouse brain after exposure to ionizing
      radiation.
AB  - Acute changes in the gene expression profile in mouse brain after exposure to
      ionizing radiation were studied using microarray analysis. RNA was isolated at
      0.25, 1, 5 and 24 h after exposure to 20 Gy and at 5 h after exposure of the
      whole brain of adult mice to 2 or 10 Gy. RNA was hybridized onto 15K cDNA
      microarrays, and data were analyzed using GeneSpring and Significant Analysis of
      Microarray. Radiation modulated the expression of 128, 334, 325 and 155 genes and
      ESTs at 0.25, 1, 5 and 24 h after 20 Gy and 60 and 168 at 5 h after 2 and 10 Gy,
      respectively. The expression profiles showed dose- and time-dependent changes in
      both expression levels and numbers of differentially modulated genes and ESTs.
      Seventy-eight genes were modulated at two or more times. Differentially modulated
      genes were associated with 12 different classes of molecular function and 24
      different biological pathways and showed time- and dose-dependent changes. The
      change in expression of four genes (Jak3, Dffb, Nsep1 and Terf1) after
      irradiation was validated using quantitative real-time PCR. Up-regulation of Jak3
      was observed in another mouse strain. In mouse brain, there was an increase of
      Jak3 immunoreactivity after irradiation. In conclusion, changes in the gene
      profile in the brain after irradiation are complex and are dependent on time and
      dose, and genes with diverse functions and pathways are modulated.

PMID- 16435914
TI  - Radiation-induced H2AX phosphorylation and neural precursor apoptosis in the
      developing brain of mice.
AB  - We showed that gamma irradiation of the developing mouse brain with 2 Gy induced
      a massive apoptosis of neural precursors but not of neurons within 24 h.
      Successive phosphorylation and dephosphorylation of histone H2AX have been linked
      to DNA breaks and repair. Similar numbers of nuclear foci of phosphorylated H2AX
      (gamma-H2AX) were found 1 h postirradiation in neural precursors and in neurons,
      suggesting that differences in radiosensitivity were not related to variations in
      the numbers of DNA double-strand breaks induced by radiation. Surviving neural
      precursors like neurons totally lost gamma-H2AX within 24 h after irradiation,
      but they had a slower kinetics of loss of gamma-H2AX foci. This suggests that the
      DNA repair machinery processed damage more slowly in these neural precursors in
      relation to their greater radiosensitivity. We also found a bright and diffuse
      gamma-H2AX staining of nuclei of cells at an early stage of apoptosis, whereas
      cells at later stages of apoptosis were unstained. This was probably related to
      phosphorylation and subsequent degradation of H2AX in the course of DNA
      fragmentation during apoptosis. Detection of gamma-H2AX-bright nuclei may thus be
      a useful marker of neural cells at an early stage of apoptosis.

PMID- 16435915
TI  - Mammary tumorigenesis in ApcMin/+ mice is enhanced by X irradiation with a
      characteristic age dependence.
AB  - The Apc(Min/+) (Min) mouse is genetically predisposed to both intestinal and
      mammary tumorigenesis. We investigated age-related changes in the susceptibility
      of mice (before, during and after puberty) to radiation-induced mammary
      tumorigenesis using this model. Female Min and wild-type mice having the C57BL/6J
      background were irradiated with 2 Gy of X rays at 2, 5, 7 and 10 weeks and killed
      humanely at 18 weeks of age. Min mice irradiated at 7-10 weeks of age (after
      puberty) developed mammary tumors with squamous metaplasia, whereas their wild
      type littermates did not. Interestingly, irradiation of Min mice at 2-5 weeks
      (before and during puberty, respectively) did not induce mammary tumors but
      rather cystic nodules with metaplasia. The mammary tumors exhibited increased
      nuclear beta-catenin protein and loss of the wild-type Apc allele. Our results
      show that susceptibility to radiation-induced mammary tumorigenesis increases
      after puberty in Min mice, suggesting that the tumorigenic effect of ionizing
      radiation targets the lobular-alveolar progenitor cells, which increase in number
      with age and are controlled by beta-catenin signaling.

PMID- 16435916
TI  - Effects of 900 MHz GSM wireless communication signals on DMBA-induced mammary
      tumors in rats.
AB  - The purpose of the study was to investigate whether exposure to 900 MHz GSM
      wireless communication signals enhances mammary tumor development and growth
      induced by low-dose DMBA. Five hundred female Sprague-Dawley rats were treated
      with a single dose of 35 mg/kg DMBA and then divided into five groups in a
      blinded fashion: one cage control group and four exposure groups, including three
      microwave exposure groups and one sham exposure with specific absorption rates
      (SARs) of 4.0, 1.33, 0.44 and 0 W/kg, respectively. Exposure started on the day
      after DMBA administration and lasted 4 h/day, 5 days/week for 26 weeks. Rats were
      weighed and palpated weekly for the presence of tumors and were killed humanely
      at the end of the 26-week exposure period. All mammary glands were examined
      histologically. There were no statistically significant differences in body
      weight between sham- and GSM microwave-exposed groups. No significant differences
      in overall mammary tumor incidence, latency to tumor onset, tumor multiplicity,
      or tumor size were observed between microwave- and sham-exposed groups. There was
      a tendency for reduction of mammary adenocarcinoma incidence in the lowest
      microwave exposure group (0.44 W/ kg) compared with the sham-exposed group (P =
      0.058). Additionally, a higher incidence of adenocarcinoma was noticed in the 4.0
      W/kg group from the 15th to 26th weeks, especially in the 19th week (P = 0.358
      compared to sham). However, neither tendency was statistically significant; thus
      this study does not provide evidence that GSM microwave exposure promotes mammary
      tumor development in rats. In the present study there were significant
      differences between the cage controls and the experimental groups (sham and
      exposure). Body weight and mammary tumor (malignant plus benign) incidence in the
      cage control group were significantly higher than in the sham- and GSM microwave
      exposed groups. The latency to the mammary tumor onset was significantly shorter
      in the cage control group than in the other groups.

PMID- 16435917
TI  - Interleukin 1beta (IL1B) signaling is a critical component of radiation-induced
      skin fibrosis.
AB  - Interleukin 1 beta (IL1B), a potent pro-inflammatory cytokine, is directly up
      regulated by radiation and is known to regulate other inflammation-related
      molecules, such as the matrix metalloproteinases (MMPs) and their endogenous
      inhibitors (TIMPs). However, the nature of the interaction of IL1B with MMPs and
      TIMPs in radiation-induced skin fibrosis is unknown. We examined the response of
      primary dermal keratinocytes, fibroblasts and endothelial cells to single
      fraction radiation (10 Gy) and compared the results to a temporal sequence of
      histology from irradiated C57BL/6 and IL1R1 knockout mice. These studies showed
      that keratinocytes are the major IL1-producing cells in vitro and that radiation
      induces an immediate and chronic elevation in the expression of IL1B mRNA in the
      skin of C57BL/6 mice. This elevation was principally early and was less
      pronounced in the IL1R1 knockout strain, which also demonstrated reduced late
      radiation fibrosis. Radiation also increased expression of MMP mRNA in C57BL/6
      mice. Finally, exogenous IL1B protein induced robust endogenous IL1B mRNA
      expression, along with a brisk increase in MMPs and collagen III, but only in the
      C57BL/6 mice. In conclusion, these data suggest that IL1B plays a critical role
      in radiation-induced fibrosis and that the increased MMPs fail to block the IL1
      related collagen accumulation.

PMID- 16435918
TI  - Mitochondrial DNA mutations in individuals occupationally exposed to ionizing
      radiation.
AB  - Mutations in a 443-bp amplicon of the hypervariable region HVR1 of the D-loop of
      mitochondrial DNA (mtDNA) were quantified in DNA extracted from peripheral blood
      samples of 10 retired radiation workers who had accumulated external radiation
      doses of >0.9 Sv over the course of their working life and were compared to the
      levels of mutations in 10 control individuals matched for age and smoking status.
      The mutation rate in the 10 exposed individuals was 9.92 x 10(-5) mutations/
      nucleotide, and for the controls it was 8.65 x 10(-5) mutations/ nucleotide, with
      a procedural error rate of 2.65 x 10(-5) mutations/nucleotide. No increase in
      mtDNA mutations due to radiation exposure was detectable (P = 0.640). In
      contrast, chromosomal translocation frequencies, a validated radiobiological
      technique for retrospective dosimetric purposes, were significantly elevated in
      the exposed individuals. This suggests that mutations identified through
      sequencing of mtDNA in peripheral blood lymphocytes do not represent a promising
      genetic marker of DNA damage after low-dose or low-dose-rate exposures to
      ionizing radiation. There was an increase in singleton mutations above that
      attributable to procedural error in both exposed and control groups that is
      likely to reflect age-related somatic mutation.

PMID- 16435919
TI  - 2004 update of dosimetry for the Utah Thyroid Cohort Study.
AB  - In the 1980s, individual thyroid doses and uncertainties were estimated for
      members of a cohort of children identified in 1965 in Utah and Nevada who had
      potentially been exposed to fallout from the Nevada Test Site. That
      reconstruction represented the first comprehensive assessment of doses received
      by the cohort and was the first large effort to assess the uncertainty of dose on
      an individual person basis. The data on dose and thyroid disease prevalence
      during different periods were subsequently used in an analysis to determine risks
      of radiogenic thyroid disease. This cohort has received periodic medical follow
      up to observe changes in disease frequency and to reassess the previously
      reported radiation-related risks, most recently after a Congressional mandate in
      1998. In a recent effort to restore the databases and computer codes used to
      estimate doses in the 1980s, various deficiencies were found in the estimated
      doses due to improperly operating computer codes, corruption of secondary data
      files, and lack of quality control procedures. From 2001 through 2004, the
      dosimetry system was restored and corrected and all doses were recalculated. In
      addition, two parameter values were updated. While the mean of all doses has not
      changed significantly, many individual doses have changed by more than an order
      of magnitude.

PMID- 16435920
TI  - Spectrum of complex DNA damages depends on the incident radiation.
AB  - Ionizing radiation induces bistranded clustered damages--two or more abasic
      sites, oxidized bases and strand breaks on opposite DNA strands within a few
      helical turns. Since clusters are refractory to repair and are potential sources
      of double-strand breaks (DSBs), they are potentially lethal and mutagenic.
      Although induction of single-strand breaks (SSBs) and isolated lesions has been
      studied extensively, little is known about the factors affecting induction of
      clusters other than DSBs. To determine whether the type of incident radiation
      could affect the yields or spectra of specific clusters, we irradiated genomic T7
      DNA, a simple 40-kbp linear, blunt-ended molecule, with ion beams [iron (970
      MeV/nucleon), carbon (293 MeV/nucleon), titanium (980 MeV/nucleon), silicon (586
      MeV/nucleon), protons (1 GeV/nucleon)] or 100 kVp X rays and then quantified
      DSBs, Fpg-oxypurine clusters and Nfo-abasic clusters using gel electrophoresis,
      electronic imaging and number average length analysis. The yields (damages/Mbp
      Gy(-1)) of all damages decreased with increasing linear energy transfer (LET) of
      the radiation. The relative frequencies of DSBs compared to abasic and oxybase
      clusters were higher for the charged particles-including the high-energy, low-LET
      protons-than for the ionizing photons.

PMID- 16435921
TI  - Targeted irradiation of Mammalian cells using a heavy-ion microprobe.
AB  - The existing focusing heavy-ion microprobe at the Gesellschaft fur
      Schwerionenforschung in Darmstadt (Germany) has been modified to enable the
      targeted irradiation of single, selected cells with a defined number of ions.
      With this setup, ions in the range from helium to uranium with linear energy
      transfers (LETs) up to approximately 15,000 keV/microm can be positioned with a
      precision of a few micrometers in the nuclei of single cells that are growing in
      culture on a thin polypropylene film. To achieve this accuracy, the microbeam
      traverses a thin vacuum window with minimal scattering. Electron emission from
      that window is used for particle detection. The cells are kept in a specially
      designed dish that is mounted directly behind the vacuum window in a setup
      allowing the precise movement and the imaging of the sample with microscopic
      methods. The cells are located by an integrated software program that also
      controls the rapid deflection and switching of the beam. In this paper, the setup
      is described in detail together with the first experiments showing its
      performance. We describe the ability of the microprobe to reliably hit randomly
      positioned etched nuclear tracks in CR-39 with single ions as well as the ability
      to visualize the ion hits using immunofluorescence staining for 53BP1 as a marker
      of DNA damage in the targeted cell nuclei.

PMID- 16435922
TI  - Dosimetry for quantitative analysis of the effects of low-dose ionizing radiation
      in radiation therapy patients.
AB  - We have developed and validated a practical approach to identifying the location
      on the skin surface that will receive a prespecified biopsy dose (ranging down to
      1 cGy) in support of in vivo biological dosimetry in humans. This represents a
      significant technical challenge since the sites lie on the patient's surface
      outside the radiation fields. The PEREGRINE Monte Carlo simulation system was
      used to model radiation dose delivery, and TLDs were used for validation on
      phantoms and for confirmation during patient treatment. In the developmental
      studies, the Monte Carlo simulations consistently underestimated the dose at the
      biopsy site by approximately 15% (of the local dose) for a realistic treatment
      configuration, most likely due to lack of detail in the simulation of the linear
      accelerator outside the main beam line. Using a single, thickness-independent
      correction factor for the clinical calculations, the average of 36 measurements
      for the predicted 1-cGy point was 0.985 cGy (standard deviation: 0.110 cGy)
      despite patient breathing motion and other real-world challenges. Since the 10
      cGy point is situated in the region of high-dose gradient at the edge of the
      field, patient motion had a greater effect, and the six measured points averaged
      5.90 cGy (standard deviation: 1.01 cGy), a difference that is equivalent to
      approximately a 6-mm shift on the patient's surface.

PMID- 16435924
TI  - Continuing education: a national imperative for school nursing practice.
AB  - Competency-based continuing education is critical to the professional development
      of school nurses to ensure the application of timely, age-appropriate clinical
      knowledge and leadership skills in the school setting. School nurses are
      responsible for a large number of students with a variety of complex and diverse
      health care needs. Benner's theory of novice to expert provides a framework for
      the development of roles and competencies in the practice of school nursing. This
      manuscript synthesizes research reviewed in 15 articles. Common themes found in
      the articles include the importance of continuing education and identified
      barriers to attainment. In response, methods to access continuing education and
      financial resources are presented.

PMID- 16435925
TI  - Oppositional defiant disorder: information for school nurses.
AB  - Oppositional defiant disorder, one of the disruptive behavior disorders, has far
      reaching consequences for the individual, family, school, community, and society.
      Early recognition allows interventions geared toward promotion of prosocial
      behaviors, possibly halting progression to the more deviant conduct disorder.
      Awareness of this disorder and associated comorbidities is the first step that
      enables the school nurse to use assessment techniques and to assist in planning
      of interventions for the child. Children at risk often show tendencies toward
      oppositional defiant disorder as early as preschool. Interventions should be in
      place by the elementary school years to interrupt the pathways that may be
      difficult or impossible to change once adolescence begins. The school nurse can
      be instrumental in educating staff about risk factors, early associated
      behaviors, and referrals. Implementation of an individualized healthcare plan
      targets specific behaviors and provides a means of observing and documenting a
      child's improvements.

PMID- 16435926
TI  - Foregone mental health care and self-reported access barriers among adolescents.
AB  - Adolescents forego mental health care in spite of self-perceived needs for
      services; this presents a significant public health problem. Using data from the
      2001 Adolescent Health Care Access Survey of 16-year-olds in Saint Louis County,
      Minnesota, we assessed barriers to mental health care among the 878 respondents
      who reported ever needing psychological or emotional counseling. Demographic
      characteristics were compared among those who had always, had sometimes, or had
      never received needed mental health care. Overall, 57% of the youths reported
      foregoing mental health care at least once. Girls and adolescents living with
      both parents were significantly more likely to have foregone care. Youths
      identified two common barriers to accessing care: "Thought or hoped the problem
      would go away" (50%) and "Didn't want parents to know" (36%). School-based
      interventions should be sensitive to mental health needs, especially among girls
      and teens living in two-parent families.

PMID- 16435927
TI  - Gender differences in health risk behaviors and physical activity among middle
      school students.
AB  - Adolescence is a period of accelerated growth and change, bridging the complex
      transition from childhood to adulthood. This period offers adolescents an
      opportunity to begin planning for their futures and to adopt healthy attitudes
      about risk behaviors that can continue into adulthood, thus setting the stage for
      a lifetime of desirable health behaviors. This study used the Youth Risk Behavior
      Survey on middle school students and examined the gender differences of health
      risk behaviors among 674 8th-graders from an urban setting. The results showed
      that males were more likely to be involved in fights, to initiate alcohol use,
      and to participate in physical activity; whereas females were more likely to try
      to lose weight with unhealthy practices, such as fasting and laxatives. School
      nurses are in a prime position to promote adolescent health in the school setting
      by providing health-related services and teaching to help students initiate and
      maintain healthy lifestyles.

PMID- 16435928
TI  - Reducing hunger-associated symptoms: the midmorning nutrition break.
AB  - This study measured the effectiveness of a 9 a.m. nutrition break after it had
      been implemented for 1 academic year at an inner-city high school. Effectiveness
      was measured by student participation rates, student and teacher evaluations of
      hunger-associated symptoms experienced by students, and teacher evaluations of
      the effects on the learning environment. Sixty-nine percent of students
      participated. The most frequently cited reason for nonparticipation was dislike
      of the food offered (53%), with an additional 15% citing problems with food
      distribution. As the frequency of participation rose, the frequency of inability
      to focus, tiredness, stomachache, headache, and midmorning hunger fell. All of
      the associations were statistically significant except for headache. Seventy-four
      percent of staff stated that the nutrition break had positive effects on the
      learning environment, and 71% referred fewer students to the school nurse.

PMID- 16435929
TI  - Assessing prevalence of emotional and behavioral problems in suspended middle
      school students.
AB  - Schools are seeing an influx of disruptive behaviors related to an increase in
      emotional and behavioral issues. In the adolescent population, emotional and
      behavioral problems are manifested in a variety of forms and often result in some
      form of discipline within the school setting. Although discipline punishes the
      unwanted behavior, it does nothing to address the reason for the behavior. This
      study examined the prevalence of emotional and behavioral problems among middle
      school students who have been suspended. Students who are suspended are the very
      children at risk for social, emotional, and mental health problems. Results from
      the study indicate significance in some of the 14 subcategories of the Student
      Behavior Survey tool, lending support toward the conclusion that emotional and
      behavioral problems may be associated with suspensions. Advocating for assessment
      of emotional and behavioral needs should be considered for students with
      discipline problems that lead to suspension.

PMID- 16435930
TI  - School nurses' support for bereaved students: a pilot study.
AB  - Children may have difficulty with schoolwork because of grief over the death of
      an important person in their lives. School nurses provide support to these
      children. This pilot study consisted of a Web-based survey completed by 6 school
      nurses in a 3-county area in Washington state. The purpose of this pilot study
      was to assess the need for additional support for bereaved children and the
      extent to which school nurses meet the needs of these students. Results indicated
      that many school nurses have large caseloads that preclude spending as much time
      with bereaved students as the nurses feel is necessary. Bereaved students exhibit
      a wide variety of grief symptoms that may interfere with learning. In addition,
      rural areas do not have adequate community bereavement resources that nurses can
      use to refer students who need help beyond that offered at school. Nurses must be
      more active in supporting students within the school setting despite limited
      resources.

PMID- 16435931
TI  - Quality of life in adolescents with type 1 diabetes who participate in diabetes
      camp.
AB  - Quality of life in adolescents with Type 1 diabetes is a growing area of interest
      in pediatric research. The complex diabetes regimen imposes challenges for an
      adolescent. Adolescents diagnosed with diabetes are a group that appears to be at
      risk for having a poor health-related quality of life. Although research supports
      the positive relationship of social support and well-being in adolescents, there
      are few studies discussing quality of life in adolescents that are based on the
      factor of social support. This study compared the quality of life in adolescents
      with Type 1 diabetes who have attended at least one diabetes camp to the quality
      of life of those who have never attended diabetes camp. Results provided evidence
      of the value of social support.

PMID- 16435933
TI  - Statistical power and parameter stability when subjects are few and tests are
      many: comment on Peterson, Smith, Martorana, and Owens (2003).
AB  - Comments on the original article "The impact of chief executive officer
      personality on top management team dynamics: One mechanism by which leadership
      affects organizational performance", by R. S. Peterson et al.. This comment
      illustrates how small sample sizes, when combined with many statistical tests,
      can generate unstable parameter estimates and invalid inferences. Although
      statistical power for 1 test in a small-sample context is too low, the
      experimentwise power is often high when many tests are conducted, thus leading to
      Type I errors that will not replicate when retested. This comment's results show
      how radically the specific conclusions and inferences in R. S. Peterson, D. B.
      Smith, P. V. Martorana, and P. D. Owens's (2003) study changed with the inclusion
      or exclusion of 1 data point. When a more appropriate experimentwise statistical
      test was applied, the instability in the inferences was eliminated, but all the
      inferences become nonsignificant, thus changing the positive conclusions.

PMID- 16435935
TI  - Forced-choice assessments of personality for selection: evaluating issues of
      normative assessment and faking resistance.
AB  - Recent research suggests multidimensional forced-choice (MFC) response formats
      may provide resistance to purposeful response distortion on personality
      assessments. It remains unclear, however, whether these formats provide normative
      trait information required for selection contexts. The current research evaluated
      score correspondences between an MFC format measure and 2 Likert-type measures in
      honest and instructed-faking conditions. In honest response conditions, scores
      from the MFC measure appeared valid indicators of normative trait standing. Under
      faking conditions, the MFC measure showed less score inflation than the Likert
      measure at the group level of analysis. In the individual-level analyses,
      however, the MFC measure was as affected by faking as was the Likert measure.
      Results suggest the MFC format is not a viable method to control faking.

PMID- 16435936
TI  - Examining assumptions about item responding in personality assessment: should
      ideal point methods be considered for scale development and scoring?
AB  - The present study investigated whether the assumptions of an ideal point response
      process, similar in spirit to Thurstone's work in the context of attitude
      measurement, can provide viable alternatives to the traditionally used dominance
      assumptions for personality item calibration and scoring. Item response theory
      methods were used to compare the fit of 2 ideal point and 2 dominance models with
      data from the 5th edition of the Sixteen Personality Factor Questionnaire (S.
      Conn & M. L. Rieke, 1994). The authors' results indicate that ideal point models
      can provide as good or better fit to personality items than do dominance models
      because they can fit monotonically increasing item response functions but do not
      require this property. Several implications of these findings for personality
      measurement and personnel selection are described.

PMID- 16435937
TI  - A meta-analytic investigation of conscientiousness in the prediction of job
      performance: examining the intercorrelations and the incremental validity of
      narrow traits.
AB  - Researchers of broad and narrow traits have debated whether narrow traits are
      important to consider in the prediction of job performance. Because personality
      performance relationship meta-analyses have focused almost exclusively on the Big
      Five, the predictive power of narrow traits has not been adequately examined. In
      this study, the authors address this question by meta-analytically examining the
      degree to which the narrow traits of conscientiousness predict above and beyond
      global conscientiousness. Results suggest that narrow traits do incrementally
      predict performance above and beyond global conscientiousness, yet the degree to
      which they contribute depends on the particular performance criterion and
      occupation in question. Overall, the results of this study suggest that there are
      benefits to considering the narrow traits of conscientiousness in the prediction
      of performance.

PMID- 16435938
TI  - Losing sleep over organizational injustice: attenuating insomniac reactions to
      underpayment inequity with supervisory training in interactional justice.
AB  - Self-reports of insomnia were collected among 467 nurses working at 4 hospitals.
      At 2 of these hospitals, a change in pay policy resulted in reduced pay for all
      nurses, whereas nurses' pay was unchanged at the other 2 hospitals. Nursing
      supervisors at 1 hospital in each group received training in promoting
      interactional justice, whereas no training was provided at the other 2 hospitals.
      Reflecting the stressful nature of underpayment, insomnia was significantly
      greater among nurses whose pay was reduced than among those whose pay remained
      unchanged. However, the degree of insomnia was significantly lower among nurses
      whose supervisors were trained in interactional justice, both immediately after
      training and 6 months later. These findings demonstrate the buffering effects of
      interactionally fair treatment on reactions to underpayment.

PMID- 16435939
TI  - Relational correlates of interpersonal citizenship behavior: a social network
      perspective.
AB  - This study examines the role of social network ties in the performance and
      receipt of interpersonal citizenship behavior (ICB), one form of organizational
      citizenship behavior (OCB). A field study involving 141 employees of a
      manufacturing firm provided evidence that social network ties are related to the
      performance and receipt of ICB. Results support hypothesized relationships, which
      are based on social exchange theory, suggesting strength of friendship is related
      to performance and receipt of ICB. Support was also found for impression
      management-based hypotheses suggesting that asymmetric influence and 3rd-party
      influence are related to the performance and receipt of ICB. These relationships
      were significant when controlling for job satisfaction, commitment, procedural
      justice, hierarchical level, demographic similarity, and job similarity.
      Implications and directions for future research are addressed.

PMID- 16435940
TI  - "Not another meeting!" Are meeting time demands related to employee well-being?
AB  - Using an interruptions framework, this article proposes and tests a set of
      hypotheses concerning the relationship of meeting time demands with job attitudes
      and well-being (JAWB). Two Internet surveys were administered to employees who
      worked 35 hr or more per week. Study 1 examined prescheduled meetings attended in
      a typical week (N=676), whereas Study 2 investigated prescheduled meetings
      attended during the current day (N=304). As proposed, the relationship between
      meeting time demands and JAWB was moderated by task interdependence, meeting
      experience quality, and accomplishment striving. However, results were somewhat
      dependent on the time frame of a study and the operational definition used for
      meeting time demands. Furthermore, perceived meeting effectiveness was found to
      have a strong, direct relationship with JAWB.

PMID- 16435941
TI  - Empowerment and team effectiveness: an empirical test of an integrated model.
AB  - The authors developed a model of team empowerment as an emergent state linking
      inputs (I) with processes (P) and, thereby, with outcomes (O) in the context of
      an expanded team IPO framework. Using survey responses from 452 members of 121
      empowered service technician teams, along with archival quantitative performance
      and customer satisfaction criteria, the authors tested the model using structural
      equation modeling techniques. The model was generally supported, although areas
      for improvement were evident. Specifically, empowerment partially mediated the
      influences of various inputs on team processes, whereas team processes fully
      mediated the influence of empowerment on outcomes. Directions for future research
      and application are discussed.

PMID- 16435942
TI  - You can take it with you: individual differences and expatriate effectiveness.
AB  - The authors report the collaborative efforts of 2 research teams that
      independently investigated the effects of stable personality traits (the Big
      Five) and specific behavioral competencies (cultural flexibility, task and people
      orientations, and ethnocentrism) on key dimensions of expatriate effectiveness:
      psychological adjustment, assignment withdrawal cognitions, and job performance.
      Analyses of multiple-source and longitudinal data from 3 studies, including a
      diverse sample of expatriates in Hong Kong and separate samples of Korean and
      Japanese expatriates posted around the world, indicate several direct effects of
      individual differences. Further data show reliable distinctions between the
      traits and competencies as well as incremental prediction by either set of
      predictors in the presence of the others.

PMID- 16435943
TI  - Hostility, job attitudes, and workplace deviance: test of a multilevel model.
AB  - The authors tested a model, inspired by affective events theory (H. M. Weiss & R.
      Cropanzano, 1996), that examines the dynamic nature of emotions at work, work
      attitudes, and workplace deviance. Sixty-four employees completed daily surveys
      over 3 weeks, reporting their mood, job satisfaction, perceived interpersonal
      treatment, and deviance. Supervisors and significant others also evaluated
      employees' workplace deviance and trait hostility, respectively. Over half of the
      total variance in workplace deviance was within-individual, and this
      intraindividual variance was predicted by momentary hostility, interpersonal
      justice, and job satisfaction. Moreover, trait hostility moderated the
      interpersonal justice-state hostility relation such that perceived injustice was
      more strongly related to state hostility for individuals high in trait hostility.

PMID- 16435944
TI  - Benefits of all work and no play: the relationship between neuroticism and
      performance as a function of resource allocation.
AB  - The authors evaluate a model suggesting that the performance of highly neurotic
      individuals, relative to their stable counterparts, is more strongly influenced
      by factors relating to the allocation of attentional resources. First, an air
      traffic control simulation was used to examine the interaction between effort
      intensity and scores on the Anxiety subscale of Eysenck Personality Profiler
      Neuroticism in the prediction of task performance. Overall effort intensity
      enhanced performance for highly anxious individuals more so than for individuals
      with low anxiety. Second, a longitudinal field study was used to examine the
      interaction between office busyness and Eysenck Personality Inventory Neuroticism
      in the prediction of telesales performance. Changes in office busyness were
      associated with greater performance improvements for highly neurotic individuals
      compared with less neurotic individuals. These studies suggest that highly
      neurotic individuals outperform their stable counterparts in a busy work
      environment or if they are expending a high level of effort.

PMID- 16435945
TI  - The impact of financial and nonfinancial incentives on business-unit outcomes
      over time.
AB  - Unlike previous behavior management research, this study used a quasi
      experimental, control group design to examine the impact of financial and
      nonfinancial incentives on business-unit (21 stores in a fast-food franchise
      corporation) outcomes (profit, customer service, and employee turnover) over
      time. The results showed that both types of incentives had a significant impact
      on all measured outcomes. The financial incentive initially had a greater effect
      on all 3 outcomes, but over time, the financial and nonfinancial incentives had
      an equally significant impact except in terms of employee turnover.

PMID- 16435946
TI  - Toward a better understanding of psychological contract breach: a study of
      customer service employees.
AB  - Experiences of psychological contract breach have been associated with a range of
      negative behavior. However, much of the research has focused on master of
      business administration alumni and managers and made use of self-reported
      outcomes. Studying a sample of customer service employees, the research found
      that psychological contract breach was related to lower organizational trust,
      which, in turn was associated with perceptions of less cooperative employment
      relations and higher levels of absenteeism. Furthermore, perceptions of external
      market pressures moderated the effect of psychological contract breach on
      absenteeism. The study indicated that psychological contract breach can arise
      when employees perceive discrepancies between an organization's espoused
      behavioral standards and its actual behavioral standards, and this can affect
      discretionary absence.

PMID- 16435947
TI  - Longitudinal examination of the role of goal orientation in cross-cultural
      adjustment.
AB  - In this longitudinal study, the authors introduced goal orientation theory to the
      study of cross-cultural adjustment. The authors examined relationships among
      dispositional goal orientation, domain-specific self-efficacy, and cross-cultural
      adjustment. Results indicated that a learning orientation was positively related
      to sojourners' academic and social self-efficacy, whereas a performance
      orientation was negatively related to sojourners' social self-efficacy.
      Sojourners' academic and social self-efficacy were positively related to academic
      and social adjustment, respectively. A learning orientation was positively
      related to academic and social adjustment, and the relationship was mediated by
      self-efficacy. A performance orientation was not related to adjustment. Finally,
      academic adjustment was positively related to grade point average. The authors
      discussed implications for research and practices.

PMID- 16435948
TI  - Self-regulation: from goal orientation to job performance.
AB  - The authors investigated the effects on job performance of 3 forms of goal
      orientation and 4 self-regulation (SR) tactics. In a longitudinal field study
      with salespeople, learning and performance-prove goal orientation predicted
      subsequent sales performance, whereas performance-avoid goal orientation
      negatively predicted sales performance. The SR tactics functioned as mediating
      variables between learning and performance-prove goal orientations and
      performance. Social competence and proactive behavior directly and positively
      predicted sales performance, and emotional control negatively predicted
      performance.

PMID- 16435949
TI  - Organizational citizenship behavior and performance evaluations: exploring the
      impact of task interdependence.
AB  - The influence of task interdependence on the importance attributed to
      organizational citizenship behavior (OCB) in evaluations of employee performance
      was investigated in 3 studies. In Study 1,238 undergraduates were exposed to a
      task interdependence manipulation and a unit-level performance manipulation and
      provided citizenship ratings. In Study 2,148 master of business administration
      students were exposed to a task interdependence manipulation and then rated the
      importance of OCB in their evaluations of employee performance. In Study 3,130
      managers rated the task interdependence in their unit of principal responsibility
      and the importance of OCB in their overall evaluations of employee performance.
      The results suggest task interdependence may affect the importance attributed to
      OCB by evaluators. Implications of these results are explored.

PMID- 16435950
TI  - Transformational leadership, initiating structure, and substitutes for
      leadership: a longitudinal study of research and development project team
      performance.
AB  - Transformational leadership, initiating structure, and selected substitutes for
      leadership were studied as longitudinal predictors of performance in 118 research
      and development (R&D) project teams from 5 firms. As hypothesized,
      transformational leadership predicted 1-year-later technical quality, schedule
      performance, and cost performance and 5-year-later profitability and speed to
      market. Initiating structure predicted all the performance measures. The
      substitutes of subordinate ability and an intrinsically satisfying task each
      predicted technical quality and profitability, and ability predicted speed to
      market. Moderator effects for type of R&D work were hypothesized and found
      whereby transformational leadership was a stronger predictor of technical quality
      in research projects, whereas initiating structure was a stronger predictor of
      technical quality in development projects. Implications for leadership theory and
      research are discussed.

PMID- 16435951
TI  - Placing perceptions of politics in the context of the feedback environment,
      employee attitudes, and job performance.
AB  - The authors proposed a model suggesting that organizational environments
      supporting high levels of informal supervisor and coworker feedback are
      associated with lower employee perceptions of organizational politics.
      Furthermore, these lowered perceptions of politics were proposed to result in
      higher employee morale (as reflected in job satisfaction and affective
      commitment) and, through morale, to higher levels of task performance and
      organizational citizenship. The proposed mediational model was supported with
      empirical results from 150 subordinate-supervisor dyads sampled across a variety
      of organizations. Higher quality feedback environments were associated with lower
      perceptions of organizational politics, and morale mediated the relationships
      between organizational politics and various aspects of work performance. These
      findings suggest that when employees have greater access to information regarding
      behaviors that are acceptable and desired at work, perceptions of politics are
      reduced and work outcomes are enhanced.

PMID- 16435952
TI  - Information privacy in organizations: empowering creative and extrarole
      performance.
AB  - This article examines the relationship of employee perceptions of information
      privacy in their work organizations and important psychological and behavioral
      outcomes. A model is presented in which information privacy predicts
      psychological empowerment, which in turn predicts discretionary behaviors on the
      job, including creative performance and organizational citizenship behavior
      (OCB). Results from 2 studies (Study 1: single organization, N=310; Study 2:
      multiple organizations, N=303) confirm that information privacy entails judgments
      of information gathering control, information handling control, and legitimacy.
      Moreover, a model linking information privacy to empowerment and empowerment to
      creative performance and OCBs was supported. Findings are discussed in light of
      organizational attempts to control employees through the gathering and handling
      of their personal information.

PMID- 16435953
TI  - Moral awareness and ethical predispositions: investigating the role of individual
      differences in the recognition of moral issues.
AB  - The impact of the role of individual ethical predispositions, preferences for
      utilitarian and formalistic ideals, on managerial moral awareness was examined in
      2 studies. Results suggested that a manager's ethical predispositions influence
      his or her responses to the characteristics of the moral issue. Both
      utilitarianism and formalism shaped moral awareness, but formalism demonstrated a
      greater capacity to do so in that formalists recognized both harm and the
      violation of a behavioral norm as indicators of the moral issue, whereas
      utilitarians responded only to harm. These findings provide support for the basic
      arguments underlying theories of moral development and offer several implications
      for the study and practice of moral awareness in organizations.

PMID- 16435954
TI  - Patterns of mean-level change in personality traits across the life course: a
      meta-analysis of longitudinal studies.
AB  - The present study used meta-analytic techniques (number of samples = 92) to
      determine the patterns of mean-level change in personality traits across the life
      course. Results showed that people increase in measures of social dominance (a
      facet of extraversion), conscientiousness, and emotional stability, especially in
      young adulthood (age 20 to 40). In contrast, people increase on measures of
      social vitality (a 2nd facet of extraversion) and openness in adolescence but
      then decrease in both of these domains in old age. Agreeableness changed only in
      old age. Of the 6 trait categories, 4 demonstrated significant change in middle
      and old age. Gender and attrition had minimal effects on change, whereas longer
      studies and studies based on younger cohorts showed greater change.

PMID- 16435955
TI  - Age changes in personality and their origins: comment on Roberts, Walton, and
      Viechtbauer (2006).
AB  - Comments on the original article "Patterns of Mean-Level Change in Personality
      Traits Across the Life Course: A Meta-Analysis of Longitudinal Studies," by B. W.
      Roberts, K. W. Walton, and W. Viechtbauer. Although Roberts et al depicted the
      present authors as proponents of the immutability of traits, in fact we have
      always acknowledged the possibility of change, and we are pleased that the
      results of their meta-analysis are consistent with our conclusions about modest
      change after age 30. We agree with B.W. Roberts et al that analyses should be
      conducted at the level of more specific traits, but prefer the 30 facets of the
      Revised NEO Personality Inventory to the Social Dominance-Social Vitality
      distinction. The origins of age changes might be found either in environmental
      influences common to all cultures or in biologically based intrinsic maturation;
      we offer some reasons for preferring the latter interpretation. Meta-analyses are
      useful but not definitive, and the resolution of the origin question lies in
      further research.

PMID- 16435956
TI  - Personality traits change in adulthood: reply to Costa and McCrae (2006).
AB  - In a response to comments by P. T. Costa, Jr., and R. R. McCrae on the current
      authors' original article, the authors show that Costa and McCrae's writings on
      personality suggest a belief in immutability of personality traits. The authors
      agree with Costa and McCrae that new personality trait models that provide an
      accurate lower order structure of personality traits are needed and explain why
      the Revised NEO Personality Inventory is not the correct model for that purpose.
      The authors provide direct evidence refuting the hypothesis that personality
      traits change only because of biologically based intrinsic maturation. The
      authors present arguments supporting the contention that meta-analyses should be
      preferred to single longitudinal studies when drawing inferences about general
      patterns of personality development. Finally, the authors point out why the
      differences between their position and Costa and McCrae's are important.

PMID- 16435957
TI  - Gender differences in temperament: a meta-analysis.
AB  - The authors used meta-analytical techniques to estimate the magnitude of gender
      differences in mean level and variability of 35 dimensions and 3 factors of
      temperament in children ages 3 months to 13 years. Effortful control showed a
      large difference favoring girls and the dimensions within that factor (e.g.,
      inhibitory control: d = -.41, perceptual sensitivity: d = -0.38) showed moderate
      gender differences favoring girls, consistent with boys' greater incidence of
      externalizing disorders. Surgency showed a difference favoring boys, as did some
      of the dimensions within that factor (e.g., activity: d = 0.33, high-intensity
      pleasure: d = 0.30), consistent with boys' greater involvement in active rough
      and-tumble play. Negative affectivity showed negligible gender differences.

PMID- 16435958
TI  - Visual complexity: a review.
AB  - The idea of visual complexity, the history of its measurement, and its
      implications for behavior are reviewed, starting with structuralism and Gestalt
      psychology at the beginning of the 20th century and ending with visual complexity
      theory, perceptual learning theory, and neural circuit theory at the beginning of
      the 21st. Evidence is drawn from research on single forms, form and texture
      arrays and visual displays. Form complexity and form probability are shown to be
      linked through their reciprocal relationship in complexity theory, which is in
      turn shown to be consistent with recent developments in perceptual learning and
      neural circuit theory. Directions for further research are suggested.

PMID- 16435961
TI  - Experimental challenges to theories of classical conditioning: application of an
      attentional model of storage and retrieval.
AB  - Several studies have recently challenged the accuracy of traditional models of
      classical conditioning that account for some experimental data in terms of a
      storage deficit. Among other results, it has been reported that extinction of the
      blocking or overshadowing stimulus results in the recovery of the response to the
      blocked or overshadowed stimulus, backward blocking shows spontaneous recovery,
      extinction of the training context results in the recovery from latent
      inhibition, interposing a delay between conditioning and testing in latent
      inhibition increases latent inhibition, and latent inhibition antagonizes
      overshadowing. An existing neural network model of classical conditioning (N. A.
      Schmajuk, Y. Lam, & J. A. Gray, 1996), which includes an attentional mechanism
      controlling both storage and retrieval of associations, is able to quantitatively
      describe these results.

PMID- 16435960
TI  - Effects of psychotherapy for depression in children and adolescents: a meta
      analysis.
AB  - Serious sequelae of youth depression, plus recent concerns over medication
      safety, prompt growing interest in the effects of youth psychotherapy. In
      previous meta-analyses, effect sizes (ESs) have averaged .99, well above
      conventional standards for a large effect and well above mean ES for other
      conditions. The authors applied rigorous analytic methods to the largest study
      sample to date and found a mean ES of .34, not superior but significantly
      inferior to mean ES for other conditions. Cognitive treatments (e.g., cognitive
      behavioral therapy) fared no better than noncognitive approaches. Effects showed
      both generality (anxiety was reduced) and specificity (externalizing problems
      were not), plus short- but not long-term holding power. Youth depression
      treatments appear to produce effects that are significant but modest in their
      strength, breadth, and durability.

PMID- 16435959
TI  - A review of sex differences in peer relationship processes: potential trade-offs
      for the emotional and behavioral development of girls and boys.
AB  - Theory and research on sex differences in adjustment focus largely on parental,
      societal, and biological influences. However, it also is important to consider
      how peers contribute to girls' and boys' development. This article provides a
      critical review of sex differences in several peer relationship processes,
      including behavioral and social-cognitive styles, stress and coping, and
      relationship provisions. The authors present a speculative peer-socialization
      model based on this review in which the implications of these sex differences for
      girls' and boys' emotional and behavioral development are considered. Central to
      this model is the idea that sex-linked relationship processes have costs and
      benefits for girls' and boys' adjustment. Finally, the authors present recent
      research testing certain model components and propose approaches for testing
      understudied aspects of the model.

PMID- 16435963
TI  - Motivational control of blocking.
AB  - Hungry and thirsty rats lever pressed for food pellets in 1 visual stimulus (V1)
      and for a saline solution in another stimulus (V2). In a 2nd phase, the rats were
      made either hungry or thirsty and pressed for a starch solution in 2 stimulus
      compounds, each containing 1 of the visual cues and an auditory cue, that is,
      V1A1 and V2A2. On test, rats responded less to A1 than to A2 when hungry but less
      to A2 than to A1 when thirsty. Two further experiments replicated this selective
      blocking effect when the rats were both hungry and thirsty during Phase 2 and
      demonstrated that the magnitude of blocking was comparable to that observed when
      the reinforcer identity was held constant across the 2 phases.

PMID- 16435962
TI  - Counteraction between overshadowing and degraded contingency treatments: support
      for the extended comparator hypothesis.
AB  - Four experiments using rats in a Pavlovian lick-suppression preparation
      investigated the effects of combining 2 treatments known for their response
      decrementing effects, namely, overshadowing and degraded contingency. Contrary to
      most contemporary learning theories, the extended comparator hypothesis predicts
      that these 2 treatments will counteract each other, and therefore, less of a
      decrement in conditioned responding should be observed than with either treatment
      alone. Experiments 1 and 2 confirmed this prediction in first-order conditioning
      and sensory preconditioning preparations, respectively. Experiment 3 demonstrated
      that posttraining extinction of the training context resulted in a recovery from
      degraded contingency and reversed the counteractive effect on overshadowing.
      Finally, Experiment 4 demonstrated that posttraining extinction of the
      overshadowing stimulus resulted in recovery from simple overshadowing and also
      reversed the counteractive effect on degraded contingency. These results are
      consistent with the extended comparator hypothesis but not traditional or recent
      acquisition-focused models.

PMID- 16435964
TI  - Spatial learning based on the shape of the environment is influenced by
      properties of the objects forming the shape.
AB  - In 3 experiments rats had to find a submerged platform that was located in a
      corner of a kite-shaped pool. The color of the walls creating this corner
      provided an additional cue for finding the platform in the shape + color
      condition but not the shape-only condition. During tests in a pool with walls of
      a uniform color but no platform, more time was spent in the corner where the
      platform was originally located after training in the shape + color than in the
      shape-only condition. The results challenge theories that assume either that
      learning about the shape of the environment takes place in a dedicated module or
      that cues compete for the control they acquire over behavior.

PMID- 16435965
TI  - How the great apes (Pan troglodytes, Pongo pygmaeus, Pan paniscus, and Gorilla
      gorilla) perform on the reversed contingency task: the effects of food quantity
      and food visibility.
AB  - S. T. Boysen and G. G. Berntson (1995) found that chimpanzees performed poorly on
      a reversed contingency task in which they had to point to the smaller of 2 food
      quantities to acquire the larger quantity. The authors compared the performance
      of 4 great ape species (Pan troglodytes, Pongo pygmaeus, Pan paniscus, and
      Gorilla gorilla) on the reversed contingency task while manipulating food
      quantity (0-4 or 1-4) and food visibility (visible pairs or covered pairs).
      Results showed no systematic species differences but large individual
      differences. Some individuals of each species were able to solve the reversed
      contingency task. Both quantity and visibility of the food items had a
      significant effect on performance. Subjects performed better when the disparity
      between quantities was smaller and the quantities were not directly visible.

PMID- 16435966
TI  - Resistance to extinction in evaluative conditioning.
AB  - A well-demonstrated phenomenon in traditional Pavlovian conditioning research
      with humans is that of experimental extinction. In contrast, human evaluative
      conditioning research suggests that evaluative learning shows marked resistance
      to extinction. Here, the authors replicate both findings concurrently. Two
      differential fear conditioning experiments with an electrocutaneous stimulus as
      the unconditioned stimulus evidenced (a) sensitivity to extinction using an
      autonomic skin-conductance measure and (b) complete resistance to extinction
      using an affective-priming measure. The results corroborate the idea that
      evaluative conditioning is more resistant to extinction than is expectancy
      learning (F. Baeyens, P. Eelen, & G. Crombez, 1995).

PMID- 16435967
TI  - Same/different abstract-concept learning by pigeons.
AB  - Eight pigeons were trained and tested in a simultaneous same/different task.
      After pecking an upper picture, they pecked a lower picture to indicate same or a
      white rectangle to indicate different. Increases in the training set size from 8
      to 1,024 items produced improved transfer from 51.3% to 84.6%. This is the first
      evidence that pigeons can perform a two-item same/different task as accurately
      with novel items as training items and both above 80% correct. Fixed-set control
      groups ruled out training time or transfer testing as producing the high level of
      abstract-concept learning. Comparisons with similar experiments with rhesus and
      capuchin monkeys showed that the ability to learn the same/different abstract
      concept was similar but that pigeons require more training exemplars.

PMID- 16435968
TI  - Prospective memory in the formation of learning sets by rhesus monkeys (Macaca
      mulatta).
AB  - In conventional discrimination learning-set formation, it is possible that rhesus
      monkeys (Macaca mulatta) learn to lay down prospective memories by anticipating
      the next trial and deciding in advance what choice will be made. To test this
      hypothesis, the authors administered discrimination problems with 24-hr
      intertrial intervals, predicting that these long intervals would disrupt or
      prevent the putative anticipation of the next trial. Confirming their
      expectation, the authors found no indication of learning-set formation under
      these conditions.

PMID- 16435969
TI  - Do Asian elephants (Elephas maximus) apply causal reasoning to tool-use tasks?
AB  - Two experiments addressed contradictory claims about causal reasoning in
      elephants. In Experiment 1, 4 Asian elephants (Elephas maximus) were pretrained
      to remove a lid from the top of a bucket and retrieve a food reward.
      Subsequently, in the first 5 critical trials, when the lid was placed alongside
      the bucket and no longer obstructed access to the reward, each elephant continued
      to remove the lid before retrieving the reward. Experiment 2, which involved 11
      additional elephants and variations of the original design, yielded similarly
      counterintuitive observations. Although the results are open to alternative
      interpretations, they appear more consistent with associative learning than with
      causal reasoning. Future applications of Fabrean methodologies (J. H. Fabre,
      1915) to animal cognition are proposed.

PMID- 16435970
TI  - The effects of distributional learning on rats' sensitivity to phonetic
      information.
AB  - During the first year of life, infants show decreased sensitivity to phonetic
      differences not used in their native language and increased sensitivity to the
      differences that are used. It has been shown that this change in speech
      perception is a function of the distributional properties of the input. The
      present study explores whether the mechanism responsible for the developmental
      changes regarding the organization of phonetic categories is a general mechanism
      shared with other animals. The results demonstrate that the distributional
      exposure to a phonetic continuum affects the subsequent discrimination of these
      phonemes in rats, indicating that the ability to use distributional cues to
      change the phonetic category structure extends beyond humans.

PMID- 16435971
TI  - Investigating the devaluation explanation for negative anticipatory contrast.
AB  - This study addressed whether negative anticipatory contrast results in a decrease
      in the value of the low-valued substance. Rats responded in training conditions
      designed to produce negative contrast. They then responded in test sessions in
      which the low-valued substance from the training sessions was the reinforcer for
      an operant response. Despite the finding of contrast in the training conditions,
      the low-valued substance was a more effective reinforcer early in testing after
      training conditions in which it had been followed by access to the high-valued
      substance than after training conditions in which it had not. The findings
      question the devaluation explanation for contrast but may be similar to other
      findings of reversals of "preference."

PMID- 16435972
TI  - Editorial policies of the American Psychologist.
AB  - This year marks the 60th anniversary of the American Psychologist (AP). Since the
      publication of its first issue in January 1946, AP has served as the flagship
      journal for the American Psychological Association (APA) and has played an
      important and unique role for the field of psychology. Because of the quality of
      the articles published in AP, the journal has evolved into one of the most
      influential and widely cited publications in psychology. The purpose of this
      editorial is to outline a revised set of policies for the journal that builds on
      and expands those developed by previous editors (see, e.g., Fowler, 1993;
      Goodstein, 1987; Kiesler, 1976; Pallack, 1981). Before outlining these policies,
      I would like to explore the relative status and influence of AP within the
      universe of psychological and social science journals.

PMID- 16435973
TI  - A contemporary learning theory perspective on the etiology of anxiety disorders:
      it's not what you thought it was.
AB  - The authors describe how contemporary learning theory and research provide the
      basis for perspectives on the etiology and maintenance of anxiety disorders that
      capture the complexity associated with individual differences in the development
      and course of these disorders. These insights from modern research on learning
      overcome the shortcomings of earlier overly simplistic behavioral approaches,
      which sometimes have been justifiably criticized. The authors show how
      considerations of early learning histories and temperamental vulnerabilities
      affect the short- and long-term outcomes of experiences with stressful events.
      They also demonstrate how contextual variables during and following stressful
      learning events affect the course of anxiety disorder symptoms once they develop.
      This range of variables can lead to a rich and nuanced understanding of the
      etiology and course of anxiety disorders.

PMID- 16435974
TI  - Arbitrary metrics in psychology.
AB  - Many psychological tests have arbitrary metrics but are appropriate for testing
      psychological theories. Metric arbitrariness is a concern, however, when
      researchers wish to draw inferences about the true, absolute standing of a group
      or individual on the latent psychological dimension being measured. The authors
      illustrate this in the context of 2 case studies in which psychologists need to
      develop inventories with nonarbitrary metrics. One example comes from social
      psychology, where researchers have begun using the Implicit Association Test to
      provide the lay public with feedback about their "hidden biases" via popular
      Internet Web pages. The other example comes from clinical psychology, where
      researchers often wish to evaluate the real-world importance of interventions. As
      the authors show, both pursuits require researchers to conduct formal research
      that makes their metrics nonarbitrary by linking test scores to meaningful real
      world events.

PMID- 16435975
TI  - Arbitrary metrics: implications for identifying evidence-based treatments.
AB  - Research designed to establish the empirical underpinnings of psychotherapy
      relies heavily on arbitrary metrics, and researchers often do not know if clients
      receiving an evidence-based treatment have improved in everyday life or changed
      in a way that makes a difference, apart from the changes the arbitrary metrics
      may have shown. In other words, it is possible that evidence-based treatments
      with effects demonstrated on arbitrary metrics do not actually help people, that
      is, reduce their symptoms and improve their functioning. Clarifying the nature of
      arbitrary metrics and assessing their implications are important initial steps.
      Needed next steps are detailing the range of strategies to better connect
      arbitrary measures to real-world referents and developing measures in which
      arbitrariness is eliminated or minimized from the start.

PMID- 16435976
TI  - The continued search for nonarbitrary metrics in psychology.
AB  - H. Blanton and J. Jaccard examined the arbitrariness of metrics in the context of
      2 current issues: (a) the measurement of racial prejudice and (b) the
      establishment of clinically significant change. According to Blanton and Jaccard,
      although research findings are not undermined by arbitrary metrics, individual
      scores and score changes may not be meaningfully interpreted. The author believes
      that their points are mostly valid and that their examples were appropriate.
      However, Blanton and Jaccard's article does not lead directly to solutions, nor
      did it adequately describe the scope of the metric problem. This article has 2
      major goals. First, some prerequisites for nonarbitrary metrics are presented and
      related to Blanton and Jaccard's issues. Second, the impact of arbitrary metrics
      on psychological research findings are described. In contrast to Blanton and
      Jaccard (2006), research findings suggest that metrics have direct impact on
      statistics for group comparisons and trend analysis.

PMID- 16435977
TI  - Consequential validity of the implicit association test: comment on Blanton and
      Jaccard (2006).
AB  - Numeric values of psychological measures often have an arbitrary character before
      research has grounded their meanings, thereby providing what S. J. Messick (1995)
      called consequential validity (part of which H. Blanton and J. Jaccard now
      identify as metric meaningfulness). Some measures are predisposed by their design
      to acquire meanings easily, an example being the sensitivity measure of signal
      detection theory. Others are less well prepared, illustrated by most self-report
      measures of self-esteem. Counter to Blanton and Jaccard's characterization, the
      Implicit Association Test (IAT) has properties that predispose it to acquire
      consequential validity rapidly. With the IAT as the subject of over 250
      publications since 1998, there is now much evidence for its consequential
      validity. The IAT has attracted more scholarly criticism than have other measures
      designed for similar purposes. The authors speculate as to why the IAT is an
      attractive target.

PMID- 16435981
TI  - Schizophrenia and the immediacy mechanism.

PMID- 16435982
TI  - How to fill a half-full glass: emotion and schizophrenia.

PMID- 16435983
TI  - Immediacy, emotion, and the filling of glasses: next round's on you.

PMID- 16435984
TI  - Motor control research requires nonlinear dynamics.

PMID- 16435985
TI  - Cinderella after the ball.

PMID- 16435987
TI  - What do cancer registry and household expenditure data in Japan tell us about
      variation in tumour burden ?
AB  - Data from the total of six Japanese Cancer Registries presently reporting to
      Cancer Incidence in Five Continents demonstrate marked variation in relative
      prevalence of cancers at particular sites, despite the genetic homogeneity of the
      Japanese population. Thus either major differences in registry procedures or
      local environment must be playing an important role and since the variation is
      clearly changing with time, the former must be considered likely. Over the last
      25 year period, incidence rates for the esophagus have been generally increasing
      in Japan, except in Miyagi where they have been persistently high. Stomach cancer
      rates are on the decrease, although the trend is not so clear in Yamagata and
      Hiroshima, while colon and rectal cancers have both demonstrated consistent
      increment throughout the period surveyed, with a remarkable correlation between
      the two sites evident on cross-registry comparisons. Continued increases have
      also been apparent in lung, kidney, urinary bladder and prostate cancers in males
      and in breast, endometrium and thyroid neoplasms in females. Cervical cancer, in
      contrast, is decreasing, although a plateau may now have been reached in Miyagi.
      In the hepatopancreatic axis, patterns have generally showed elevation followed
      by a recent reduction, although without correlations among liver, gallbladder and
      pancreas rates at the cross-registry level. Common lifestyle factors may to some
      extent underly the increases seen in colon, breast, urinary bladder and thyroid
      incidence rates, given the significant relations apparent for these in the latest
      data across registries. Whether analysis of variation in dietary intake and
      exposure to other risk factors, for example using data for household expenditure,
      may provide clues to explaining the variation apparent across Japan is a question
      warranting further consideration. If so an expanded role for the cancer registry
      could well be envisaged.

PMID- 16435988
TI  - Suppressive effects of Okinawan food items on free radical generation from
      stimulated leukocytes and identification of some active constituents:
      implications for the prevention of inflammation-associated carcinogenesis.
AB  - Okinawa prefecture in Japan is a distinct area characterized by unique
      traditional food habits and longevity. Prolonged exposure to activated
      leukocytes, playing pivotal roles in chronic inflammation-associated
      carcinogenesis, is known to lead to oxidative and nitrosative damage to
      macromolecules in the body since they are primary sources of free radicals, such
      as superoxide anion (O(2)(-)) and nitric oxide (NO). In this study, we estimated
      anti-oxidative and anti-nitrosative activities of Okinawan food items by
      employing two cellular experimental systems: (1) phorbol ester-induced O(2)(-)
      generation from differentiated HL-60 human promyelocytic leukemia cells; and (2)
      lipopolysaccharide (LPS)-induced NO generation in RAW264.7 murine macrophages. A
      total of 138 food items, consisting of 42 samples unique to Okinawa and 96 common
      in the Japanese main island, were purchased at local markets in Okinawa and
      extracted with chloroform. When tested at a concentration of 100 microg/ml, 38%
      (16/42) of the former showed 70% or more inhibition of O(2)(-) generation while
      21% (20/96) of the latter did so. In parallel, 64% (27/42) of the former showed
      significant NO generation suppression in contrast to 48% (46/96) of the latter .
      Twenty-one active species were further tested at a concentration of 20 mug/ml,
      and eleven species, including sugar cane, wild turmeric, and zedoary, were
      indicated to be most promising items with anti-oxidative and anti-nitrosative
      properties. In addition, some of the active constituents (chebulagic acid, a
      resveratrol derivative, and sesquiterpenoids) were identified. Our results
      suggest that food items typical in the Okinawa area have higher cancer preventive
      potential than those common in Japan.

PMID- 16435989
TI  - Respiratory cancer population-based survival in Mumbai, India.
AB  - Survival experience of patients with cancer of the larynx (ICD-32) or lung (ICD
      34) registered by the Mumbai (Bombay) population based cancer registry, India,
      during the years 1992-94 was determined. The vital statistics of the patients
      were established by matching with death certificates from the Mumbai Municipal
      death register and by active methods such as telephone enquiry, reply-paid postal
      enquiry, house visits and scrutiny of case records. Of the 1905 (675 larynx and
      1230 lung) eligible cases for analysis, 1480 were dead (450 larynx and 1030 lung)
      and 425 were alive (225 larynx and 200 lung). The overall 5-year observed and
      relative survival rates for laryngeal cancers were 29.1% and 36.4%, and for lung
      cancers were 12.5% and 15.9% respectively. On multivariate analysis, age,
      treatment and clinical extent of disease emerged as independent predictors of
      survival with both cancers. People aged 55 years and above had a relative risk of
      four or more for laryngeal cancer and 2.3 times and more for lung cancer death as
      compared to those aged less than 35 years. Early detection and prompt treatment
      should improve overall survival from lung as well as laryngeal cancer.

PMID- 16435990
TI  - Methodology to identify Iranian immigrants for epidemiological studies.
AB  - Determining ethnic differences in cancer patterns using administrative databases
      is often a methodological challenge for information on ethnicity or place of
      birth is commonly lacking. This paper describes the approach we used to identify
      Iranians residing in British Columbia (BC), Canada and who were registered within
      the BC Cancer Registry. A listing of common Iranian surnames and given names was
      generated from two sources: a residential telephone book (with a high density of
      Iranians) and a provincial breast cancer screening program (which allowed for the
      selection of women born in Iran). Surnames and given names were reviewed manually
      and the Iranian names were identified and coded as 'highly probable' and
      'probable' Iranian. A name directory was then created and linked with the BC
      Cancer Registry to identify Iranian cancer cases. Using this method, 1729
      surnames and 737 given names were selected from the telephone book, and 1881
      surnames and 757 given names from the screening program. The majority of these
      names were coded as 'highly probable' Iranian (98% and 96% for surnames and given
      names, respectively). 12% of surnames and 10% of given names were common to both
      sources. A listing of the most common Iranian surnames and given names is
      provided. In conclusion, in the absence of other ethnicity data, surnames and
      given names can be very helpful to identify persons of specific ethnicities when
      these ethnic groups have distinctive names.

PMID- 16435991
TI  - Inhibition of Heinz body induction in an in vitro model and total antioxidant
      activity of medicinal Thai plants.
AB  - Herbs have been used for medicinal purposes for centuries and known to possess
      antioxidant properties that may help to reduce the risk of chronic diseases,
      cardiovascular disease, and cancer. We screen aqueous extracts from 20 medicinal
      plants in Thailand that were believed to possess anti-tumor activity, help immune
      stimulating property and maintain blood stasis. The antioxidant activities were
      investigated in two bioassays. Firstly, we demonstrated inhibition of Heinz
      bodies induction caused by oxidants under in vitro condition. The percentages of
      Heinz body inhibition activity in plant extracts from Terminalia citrina, Cassia
      timoriensis, and Derris elliptica were the highest followed by Anamirta cocculus,
      and Oroxylum indicum respectively. In addition, we investigated total antioxidant
      activity in plant extracts by improved ABTS radical cation decolorization assay.
      The total antioxidant activity of the extract from Terminalia citrina was also
      the highest activity followed by Ficus pubigera, Derris elliptica, Anamirta
      cocculus, Caesalpinia sappan, and Oroxylum indicum respectively. Our results
      suggest medicinal Thai plants as valuable sources of antioxidants, which may have
      a potential anti-carcinogenic activity.

PMID- 16435992
TI  - The ACE gene polymorphism is associated with the incidence of gastric cancer
      among H. pylori seropositive subjects with atrophic gastritis.
AB  - Studies of the angiotensin converting enzyme (ACE) I/D polymorphism have provided
      evidence that the D/D genotype is associated with gastric tumor progression and
      numbers of lymph node metastases, but not with the overall risk of gastric
      cancer. The highest levels of circulating and tissue ACE activity were found in
      carriers of the D/D genotype. Here, we further investigated the association using
      454 Japanese subjects undergoing a health checkup and 202 gastric cancer
      patients. The ACE polymorphism was not found to be linked with H. pylori
      seropositivity or gastric atrophy. However, among H. pylori seropositive subjects
      with atrophy, those with the I/D genotype had an increased risk of gastric cancer
      (OR=1.59; 95% CI, 1.02-2.48). We also established that the polymorphism did not
      lower the age at diagnosis of gastric cancer. Confirmation of the association
      between ACE polymorphisms and development of gastric cancer requires much larger
      studies, and the biological role also needs to be fully elucidated.

PMID- 16435993
TI  - Karyotyping in retinoblastoma--a statistical approach.
AB  - PURPOSE: Karyotype analysis in hereditary retinoblastoma is considered to be of
      marginal value in risk prediction due to uncertainties in the assessment of 13q14
      deletions. However, it is a low cost genetic test for retinoblastoma in
      developing countries. In the present study, the results of karyotype analysis
      were refined by a statistical method to overcome limitations. METHODS: Karyotype
      analysis was performed by trypsin-Giemsa banding and naked eye karyotyping for 33
      bilateral, 25 unilateral and one regressed retinoblastoma patients. The
      percentage of metaphases with 13q14 deletions in each case was plotted on a
      scatter diagram. Normalization of the data was achieved by log transformation and
      the results were statistically analyzed by one-sample 't' test using SPSS version
      9.0. RESULTS: Seven samples had 13q14 deletion percentages above the cutoff
      value. One-sample 't' test showed significance (p< 0.001). By this method, two
      unilateral and five bilateral patients had 13q14 deletions, constituting 11.8 %
      of cases. CONCLUSION: For accuracy, statistical analysis should be considered as
      an adjunct in karyotyping.

PMID- 16435994
TI  - Control of acute myeloid leukemia morbidity in northwest Iran.
AB  - BACKGROUND: To investigate protocols of remission induction therapy for
      prevention of morbidity of acute myeloid leukemia. MATERIALS AND METHODS: The
      responses of 150 patients to "2+5" and "3+7" protocols during 1996-2003 were
      assessed and analyzed with the Chi-Square method. RESULTS: Complete remission was
      observed in 30% of cases treated with 2 days of daunorubicin and 5 days of
      cytarabine (2+5 regimen). Remission was increased to 52.5% when patients were
      treated with 3+7 regimens with the same drugs. Partial remission resulted in 25
      and 10 percent of cases, respectively. CONCLUSION: As in previous studies the 3+7
      regimen was demonstrated to be more effective than the 2+5 regimen in our
      hospital (p=0.0009).

PMID- 16435995
TI  - Cancer profile of Hyderabad, Pakistan 1998-2002.
AB  - Hyderabad is the third largest city of Pakistan, the second largest city of Sindh
      Province and one of the oldest cities of the sub-continent. This administrative
      headquarter is located just east of the River Indus and is an important
      commercial and industrial center. Once a provincial capital, it is at a distance
      of approximately 200-km from Karachi. This present study was conducted with the
      objective of providing the cancer profile of Hyderabad, which has an urban
      population of 2,840,653 (52.2% M, 47.8% F) annual growth rate 1.13. The city is
      inhabited by all ethnicities of the country, however the predominant ethnicity is
      Sindhi, followed by Mohajirs (post-partition immigrants from India), and a lesser
      extent other ethnicities of Pakistan viz. Baluchs, Punjabis and Pathans. The
      study includes two sets of patients. First the incident cancer cases, residents
      of Hyderabad, who reached Karachi for diagnosis or treatment. Second the incident
      cancer cases registered at the Aga Khan University Pathology-based Cancer
      Registry (APCR) Pathology collection points at Hyderabad and subsequently
      registered at APCR, during 1st January 1998 to 31st December 2002. The pathology
      department of the AKU has 3 centers in Hyderabad, which provide diagnostic
      pathology especially oncopathology services to the city. The age-standardized
      rates (ASR) for cancer (all sites) 1998 to 2002 in Hyderabad were 91.6/100,000 in
      males and 96.0/100,000 in females. The most common malignancies (ASR per 100,000)
      in males were oral cavity (11.8), lymphoma (10.6), lung (8.0), urinary bladder
      (6.8), prostate (4.8), liver (4.4), pharynx (4.2), colo-rectum (3.6), larynx
      (3.2), and skin (3.2). The cancers in females (ASR per 100,000) were breast
      (22.4), oral cavity (11.5), gall bladder (4.8), esophagus (4.2), cervix (3.6),
      ovary (3.4), colo-rectum (3.4), lymphoma (3.4), uterus (3.4), and thyroid (2.4).
      Tobacco-associated cancers were responsible for approximately 40.0% of the tumors
      in males and 20.0% in females. Histological confirmation remained 96.3%, with
      44.5% presenting in grade II or I, 55.5% presenting as stage III and IV.
      Information on grade and stage of malignancy was available in 70% and 50% of the
      cases respectively. Males comprised 53.1%, and females 46.9% of the cases. The
      mean age of cancer all sites, both genders was 45.2 years (95% CI 44.4; 45.9),
      males 45.4 years (95% CI 44.3; 46.5); females 44.9 years (95% CI 43.9; 45.9).
      Conclusions drawn from this database must be interpreted with care, as it may be
      identified as data from selected medical institutions. Chances of selective
      collection bias are minimized as the data of the AKU pathology is collected from
      multiple centers in the city of Hyderabad, dispersed at distances, which allows
      adequate sampling from the entire city. There is a slight preponderance of
      lymphomas in males which we feel is a true higher risk, yet it may indicate an
      over representation of easily accessible sites in pathology based-data.
      Nonetheless, this is the first attempt to determine the cancer incidence pattern
      of Hyderabad, and should serve as a guideline for estimation of the cancer burden
      and risk assessment statistics of Pakistan and the cancer control program of the
      country.

PMID- 16435996
TI  - Clinicopathologic predictors of incomplete excision after loop electrosurgical
      excision for cervical preneoplasia.
AB  - The aim of this study was to identify the factors affecting incomplete excision
      after the loop electrosurgical excision procedure (LEEP) for evaluation and
      treatment of cervical neoplasia. Patients with abnormal cervical cytology who
      underwent colposcopy and LEEP at Chiang Mai University Hospital between October
      2004 and July 2005, were retrospectively evaluated. During the study period, 201
      patients were eligible for analysis. All cone margin involvement was observed in
      44% of the patients (95% CI, 37.3-51.4). Multivariate analysis revealed that
      invasive cancer on cytology (adjusted odds ratio [aOR] =3.05, 95% confidence
      interval [CI] =1.03 to 9.00; P=0.02), invasive cancer on LEEP histopathology
      (aOR=9.73, 95%CI =3.95 to 23.9; P<0.001), and a cone length of less than 10 mm
      (aOR =1.95, 95%CI =1.04 to 3.66; P =0.03) were significant predictors for any
      cone margin involvement. For endocervical margin involvement, postmenopausal
      status and a cone length of less than 10 mm were significant predictors of
      incomplete excision. In contrast to endocervical margin involvement,
      postmenopausal status was significantly associated with a decreased risk of
      ectocervical margin involvement. Invasive cancer on histopathology was a
      significant predictor of both ecto- and endocervical margin involvement. In
      conclusion, invasive cancer either on cytology or LEEP specimens and a cone
      length of less than 10 mm are significant predictors of incomplete excision.

PMID- 16435997
TI  - The metabolic syndrome is associated with increased risk of colorectal adenoma
      development: the Self-Defense Forces health study.
AB  - The metabolic syndrome, a cluster of metabolic abnormalities linked to insulin
      resistance, has attracted much interest as a risk factor for cardiovascular
      disease and type 2 diabetes. Hyperinsulinemia is also a postulated biological
      risk factor for colorectal carcinogenesis. We therefore here examined the
      relation between the metabolic syndrome and colorectal adenoma development. The
      study subjects were 756 cases of colorectal adenoma and 1751 controls with no
      polyps who underwent total colonoscopy during the period January 1995 to March
      2002 at two Self Defense Forces (SDF) hospitals in Japan. The metabolic syndrome
      was defined with reference to abdominal obesity in combination with any two of
      the following conditions: elevated triglycerides (150 mg/dL); lowered HDL
      cholesterol (<40 mg/dL); elevated blood pressure (systolic blood pressure 130
      mmHg and/or diastolic blood pressure 85 mmHg); and raised fasting glucose (110
      mg/dL). Abdominal obesity was defined as a waist circumference of 85 cm or
      more(Japanese criterion) or 90 cm (Asian criterion). Statistical adjustment was
      made for age, hospital, and rank in the SDF. The metabolic syndrome was found to
      be associated with a moderately increased risk of colorectal adenomas whether
      either of the Japanese and Asian criteria was used; adjusted odds ratios with the
      Japanese and Asian criteria were 1.38 (95% confidence interval [CI] 1.13-1.69)
      and 1.48 (95% CI 1.13-1.93), respectively. Increased risk was more evident for
      proximal than distal colon or rectal adenomas, and was almost exclusively
      observed for large lesions (5 mm in diameter). Thus the metabolic syndrome
      appears to be an important entity with regard to the prevention of colorectal
      cancer, as well as cardiovascular disease and type 2 diabetes.

PMID- 16435998
TI  - A low fat diet rich in fruits and vegetables may reduce the risk of developing
      prostate cancer.
AB  - BACKGROUND: Diet has been implicated in prostate cancer risk and there is
      evidence of risk reduction with a healthy diet. The objective of this population
      based case control study was to examine whether a low fat diet rich in fruits and
      vegetables can reduce the risk of developing prostate cancer in Mumbai, India.
      METHODS: Included in this study were microscopically proved cases of prostate
      cancer diagnosed during 1998 to 2000 and registered by Bombay Population Based
      Cancer Registry (n=594). The controls were healthy men belonging to the resident
      general population of Mumbai, India. Two controls for each case matched by age
      and place of residence were selected as the comparison group. Data on oil/fat
      consumption, fruits and vegetable consumption and other probable confounding
      factors were obtained by structured face-to-face interview. After exclusions, 390
      cases and 780 controls were available for final analysis and confounding was
      controlled by multiple logistic regression. RESULTS: 58.7% of the control group
      consumed more than 3 kg of fruits and vegetables per week compared to 52.1% of
      the case group. Controlling for age and probable confounding factors, a
      statistically significant protective effect for prostate cancer was observed for
      those who consumed fruits and vegetables 2 to 3 kg (OR 0.5, 95%CI 0.3-0.8) and
      more than 3 kg (OR 0.4, 95% CI 0.3-0.6) per week compared to those who consumed
      less than 2 kg per week. The linear trend for the protective effect was highly
      significant with increase in the consumption of fruits and vegetables (p =
      0.001). Even though not statistically significant, oil/fat consumption showed an
      elevated risk (OR 1.7, 95%CI 0.9-3.3) for those who consumed more than 2 kg of
      oil/fat per month compared to those who consumed less than 1 kg. CONCLUSION: The
      findings from this study support the hypothesis that a low fat diet rich in
      fruits and vegetables may reduce the risk of prostate cancer.

PMID- 16435999
TI  - Analysis of gastrointestinal malignancies at the Armed Forces Institute of
      Pathology (AFIP), Rawalpindi, Pakistan.
AB  - OBJECTIVES: To determine the pattern of gastrointestinal (GI) malignancies in
      northern Pakistan. DESIGN: A retrospective pathology based tumour registry data
      analysis. PLACE AND DURATION: January 1992 to December 2001 at the Armed Forces
      Institute of Pathology, Rawalpindi, Pakistan. MATERIALS AND METHODS: All
      histologically diagnosed malignant tumours of GI tract registered with the tumour
      registry were retrieved from the case files. Basic epidemiological data regarding
      each case was collected from the request forms and then analysed for the site of
      involvement, age distribution and histological types of tumours. RESULTS: During
      the study period a total of 2279 patients had GI tract malignancies, constituting
      10.8% of all malignant tumours diagnosed in this period. Males were more
      frequently affected than females (M:F ratio 2.3:1). Peak incidence was in the 50
      60 year age group. Colorectal tumours were most frequent (44.6%), followed by
      stomach (24%), esophagus (22.6%), anal (4.6%) and small intestinal (3.7%)
      malignancies. Ten cases of malignant tumours of the appendix, 6 in females and 4
      in males were also found. The histological pattern was predictable. Statistical
      analysis showed that there was significant increase (P<0.01) in registration of
      stomach, anorectal and small intestinal tumours over the period studied,whereas
      esophagus and colorectal tumours remained the same. CONCLUSION: Colorectal
      tumours are more frequent in our material as compared to other developing
      countries. Peak incidence is in slightly younger age group and cases in <20 years
      age group are also more frequent as compared to Western studies.

PMID- 16436000
TI  - Chromosome 3p alterations in northeastern Thai women with cervical carcinoma.
AB  - The purpose of this study was to determine the incidence of the loss of
      heterozygosity (LOH) among normal cervixes, cervical intraepithelial neoplasias
      (CINs) and invasive cervical cancers (ICCs). DNA samples (136) were obtained from
      31 normal cervixes, 49 CINs and 56 ICCs. Four polymorphic microsatellite markers
      (D3S1300, D3S1351, D3S1478 and D3S4103) covering the chromosome 3p arm, were
      employed. LOH at one or more loci were identified in: 9/31 (8.1%) normal
      cervixes, 17/49 (14.6%) CINs and 26/56 (22.1%) invasive cancers. The incidence of
      the LOH at 3p varied for each locus and ranged from 5.6% for D3S1351 to the
      highest rate of 16.6% for D3S1300. We thus found that LOH of chromosome 3p can
      occur in normal cervixes and that incidences increase in CINs and ICCs. Deletion
      in the 3p14.2 (D3S1300) and 3p21.2 (D3S1478) regions might be an early event and,
      in fact, necessary for cervical cancer progression. The loss of function of tumor
      suppressor genes (TSGs) located in these regions may have a sequential effect in
      cervical cancer carcinogenesis.

PMID- 16436001
TI  - Iron, cholesterol, and the risk of cancer in an 18-year cohort.
AB  - The iron catalyzed oxidation of serum lipids is hypothesized to generate
      oxidative stress, which appears to play an important role in the pathogenesis of
      many cancers. Previous research has obtained conflicting results regarding the
      independent contribution of cholesterol and iron on cancer risk. The purpose of
      this study was to test for an interaction between iron and cholesterol on cancer
      risk. The present cohort study was an analysis of the National Health and
      Nutrition Examination Survey I (NHANES I) database linked with the NHANES I
      Epidemiologic Follow-up Study. Baseline serum iron and total cholesterol values
      were obtained on 7,448 adults, who were followed for the development of cancer
      over 18-21 years. Population weights were applied to create Cox proportional
      hazard models of time to the development of cancer for the entire U.S. adult
      population (n=72,602,523). Control variables included: age, race, gender,
      smoking, body mass index, chronic cough, chronic hepatitis, chronic/recurrent
      colitis or enteritis, and gastrointestinal bleeding. Independent elevations of
      either iron or total cholesterol were not significantly related to the
      development of cancer in the adjusted model. However, the combination of iron and
      total cholesterol above the 75th percentile was associated with a significant
      increase in the risk of all cancers (HR 1.39, 95% CI 1.00-1.94). Iron and
      cholesterol above the 80th and 85th percentiles increased the hazard ratio for
      cancer further to 1.51 (CI 1.10-2.08) and 1.61 (CI 1.07-2.43), respectively.
      These results support the theory that the iron induced oxidation of serum lipids
      is important in the pathogenesis of cancer.

PMID- 16436002
TI  - Decrease in the esophageal cancer incidence rate in mountainous but not level
      parts of Cixian County, China, over 29 years.
AB  - BACKGROUND: Cixian county has one of the highest incidence rates of esophageal
      cancer (EC) in China, as well as the world. In 1974, the Cixian population-based
      cancer registry system was established, so that there is now information on
      esophageal cancer cases over almost 30 years. METHODS: Data from Cixian Cancer
      Registry were checked and analyzed using SPSS 11.5. RESULTS: From 1974 to 2002, a
      total of 18,471 new esophageal cancer cases were registered in Cixian, 11,068 in
      males and 7,403 in females. The age standardized incidence rate (ASR) for males
      was 208.77 per 100,000, while for females it was 120.47 per 100,000. There was a
      clear trend for decrease overall in the incidence rate of esophageal cancer over
      the 29 years (X(2)=19.94, P<0.001). As to the geographic distribution, the
      incidence rate in mountainous and hilly areas showed a significant decline (X(2)
      = 195.00 and X(2) = 46.08, respectively, both P X(2)0.001). Data for esophageal
      cancer incidence in level land areas in contrast were relatively steadily, with
      increase in recent years. CONCLUSION: Esophageal cancer has decreased in Cixian
      county during the last 29 years, but this is due to change in mountainous and
      hilly areas. Compared to other regions in the world, Cixian county still has a
      very high incidence of ECs.

PMID- 16436003
TI  - Ethanolic neem (Azadirachta indica) leaf extract induces apoptosis in the hamster
      buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8 and
      caspase 3.
AB  - Induction of apoptosis is one of the most active strategies in cancer
      chemoprevention and the ability of medicinal plants in this regard has attracted
      major research interest. The present study was designed to investigate the
      apoptosis inducing capacity of an ethanolic neem leaf extract (ENLE) during 7,12
      dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis
      using the apoptosis-associated proteins Bcl-2, Bim, caspase 8 and caspase 3 as
      markers. Topical application of DMBA to the hamster cheek pouch for 14 weeks
      resulted in well developed squamous cell carcinomas associated with increased
      expression of Bcl-2 and decreased expression of Bim, caspase 8 and caspase 3.
      Administration of ENLE inhibited DMBA-induced hamster buccal pouch (HBP)
      carcinogenesis, as revealed by the absence of neoplasms, with induction of Bim
      and caspases 8 and 3 and inhibition of Bcl-2 expression. Our results suggest that
      the chemopreventive effects of ENLE may be mediated by induction of apoptosis.

PMID- 16436004
TI  - Reproducibility of a semi-quantitative food frequency questionnaire in Chaoshan
      area, China.
AB  - OBJECTIVE: To examine reproducibility of assessed intake of foods and nutrients
      according to a semi-quantitative food frequency questionnaire (SQFFQ) in adult
      doctors and nurses residing in Chaoshan area of China. SUBJECTS: The SQFFQ was
      administered first in October to December of 2004 to 120 adult doctors and nurses
      living in Chaoshan area of China and was then re-administered to 102 three months
      later between January and March of 2005 (SQFFQ 1 and SQFFQ 2). METHODS:
      Reproducibility was evaluated in terms of consumption of 10 food groups and
      energy and 34 macro- and micro-nutrients based on the SQFFQ from the 102 doctors
      and nurses. RESULTS: For intake of foods, Pearsom's correlation coefficients
      (CCs) with log-transformation and energy adjustment (minimum - median - maximum)
      range from 0.43 (eggs) - 0.84 - 0.90 (teas). Spearman's rank CCs with energy
      adjustment ranged from 0.77 (cereals) - 0.84 - 0.94 (milks). Kappa statistics
      with energy adjustment ranged from 0.53 (vegetables) - 0.63 - 0.82 (teas). For
      consumption of nutrients, Pearson's correlation coefficients (CCs) with log
      transformation and energy adjustment (minimum - median - maximum) range from 0.83
      (docosahexaenoic acid and oryzanin) - 0.88 - 0.90 (linolenic acid, vitamin A,
      folic acid, vitamin E, calcium, sodium, selenium and magnesium). Spearman's rank
      CCs with energy adjustment ranged from 0.81 (oryzanin and vitamin C) - 0.86 -
      0.90 (sodium). Kappa statistics with energy adjustment ranged from 0.49 (protein)
      - 0.60 - 0.77 (sodium). CONCLUSION: Substantially high reproducibility was
      observed; it is possible to use the tailored, relatively simple, but
      comprehensive, self-administered SQFFQ to facilitate assessment of the
      association between lifestyle and health/disease in large-scale epidemiological
      studies.

PMID- 16436005
TI  - Immunohistochemical evaluation of p27 (kip1) in pleomorphic adenomas and adenoid
      cystic carcinomas of the minor salivary glands.
AB  - BACKGROUND: p27(kip1), a universal cyclin-dependent kinase inhibitor, is a useful
      marker for predicting clinical aggressiveness with various human tumors. In this
      study, p27 expression was investigated in pleomorphic adenomas (PAs) and adenoid
      cystic carcinomas (ACCs) of minor salivary glands to evaluate its utility for
      differentiation purposes. At the same time, the correlation between p27 and ACC
      grading was evaluated. MATERIALS AND METHODS: Clinicopathological features of 22
      patients (11 ACCs, 11 PAs), including age, sex and size of tumor were obtained
      from medical records. Immunohistochemical staining with p27(kip1) was performed
      for each specimen and p27 labelling indices were determined with a computer
      assisted image-analyzing system (CAS 200). Pearson's correlation coefficient,
      Spearman's correlation coefficient, Students t-test, Kruskal-Wallis test and
      ANOVA were applied for statistical analyses using SPSS 11.5. RESULTS: p27 LIs for
      all PAs were above 25% whereas for ACCs they were under 25% (except one case).
      p27 expression (LI and intensity) was significantly lower in ACCs than PAs. The
      correlation between p27 expression and ACC grading was not significant.
      CONCLUSION: Overall, these findings suggest that reduced expression of p27 might
      be correlated with the development of ACC and could be an indicator of malignant
      behavior.

PMID- 16436006
TI  - Diffuse large B cell lymphoma (DLBCL) in Pakistan: an emerging epidemic?
AB  - There has been a recent concern among oncological clinicians and pathologists of
      our region regarding the disproportionate increase in the number of patients
      presenting with diffuse large B cell lymphoma (DLBCL). This prompted us to
      conduct a thorough, hospital-based epidemiological study in a major referral
      center of Pakistan. A total of 780 specimens were collected over last half decade
      from cases classified as adult Non Hodgkin's lymphoma (NHL). Out of these 780,
      596 (76.4 %) were diagnosed as DLBCLs. The gender ratio was 2.3:1 (M:F) and the
      median age was 47.2 years, with an age range of 15-85 years. Nodal-NHLs
      constituted 42.2 % of all adult NHLs, with the cervical lymph nodes as the most
      frequent nodal site of presentation. The most frequent extranodal site was the
      gastro-intestinal tract (GIT), followed by the head and neck. In conclusion, we
      document an astonishingly high number of DLBCL amounting to an emerging epidemic
      in Pakistan, with a consideration of probable etiopathogenetic factors.

PMID- 16436007
TI  - Alpha fetoprotein for screening for hepatocellular cancer in populations with
      viral hepatitis B: an appraisal of Thai reports.
AB  - Hepatocellular cancer (HCC) is a common gastrointestinal malignancy in hepatitis
      cases which is difficult to detect in early stages. Alpha fetoprotein (AFP) is a
      tumor marker which has been introduced for screening but in Southeast Asia where
      the rate of hepatitis B seropositivity is very high, the diagnostic benefit is
      still doubtful. Here, a literature review of three Thai reports was conducted,
      covering 4,295 cases. The overall diagnostic activity showed sensitivity,
      specificity, false positives and false negatives of 73.5%, 98.9%, 26.5% and 1.1%,
      respectively. Thus the sensitivity is insufficient for screening purposes and
      serum AFP can not be recommended for hepatitis B carriers over standard tests.

PMID- 16436008
TI  - Demographic and anatomical survey of colorectal polyps in an Iranian population.
AB  - OBJECTIVE: Asian countries generally have low incidences of colorectal cancers
      (CRCs). One approach to prevention is based on recognition and removal of polyps.
      The aim of this study was to determine basic demographic features, anatomic
      distribution and characteristics of colorectal polyps in a local Asian population
      for comparison with western data. METHODS: We here performed a retrospective
      chart review of 194 patients with colorectal polyps detected by endoscopy [total
      colonoscopy in 136 cases (73.1%), and flexible sigmoidoscopy in the remainder]
      during 1992-2005, focusing on descriptive statistics for categorical variables,
      including distribution pattern and histology. Cold biopsy in 14 cases, piecemeal
      endoscopic resection in 5 patients, and usual snare polypectomy in the remainder
      were performed. Patients with polyposis syndromes were excluded from the
      analysis. RESULTS: The average age of patients was 43.2 yr (range 2-80) with 71%
      being males. Most of the polyps were presented in 5th decade (p=0.029). A total
      of 32 (17.2%) had synchronous proximal polyps (15% adenomas), and 154 cases had
      solitary polyps. The vast majority of the polyps were left sided and the most
      frequent type was adenoma (63%), with a villous component in 37.1%. Coexistent
      cancer was seen in 10.9% of cases. CONCLUSION: In this Iranian population, the
      majority of polyps are left sided. The incidence of adenomas and their histology
      appear comparable to data for western patients, but with a significantly lower
      rate for synchronous neoplastic lesions.

PMID- 16436009
TI  - Ethnicity greatly influences the interleukin-1 gene cluster(IL-1b promoter, exon
      5 and IL-1Ra) polymorphisms: a pilot study of a north Indian population.
AB  - There is considerable evidence that polymorphisms in the regulatory regions of
      cytokine genes are highly influenced by ethnicity. Polymorphisms in interleukin 1
      beta (IL-1beta) and IL-1 receptor antagonist (IL-1Ra) genes, respectively
      encoding a potent inflammatory agent and an antagonist, which combines with IL-1
      receptors competitively, have been associated with a number of diseases like
      systemic lupus erythematosus, rheumatoid arthritis, sepsis, kidney diseases, and
      cancer. In this study, we therefore evaluated the distribution of interleukin-1
      gene cluster (IL-1beta promoter region, exon-5 and IL-1Ra) gene polymorphisms in
      206 healthy north Indian subjects, using PCR-based restriction analysis. We also
      constructed various haplotypes and estimated the linkage disequilibrium (LD). We
      found that genotype and allelic frequencies for these cytokines were
      conspicuously different when compared among different ethnic populations. The
      haplotype 'T-E1-1' predominated (41.7%) while the least common was 'C-E2-2' (2%)
      in our population. Genetic linkage between three loci of IL-1 gene showed strong
      association among the variants in controls (D'=0.42, p<0.001). Our results
      suggest that the frequency and distribution of the polymorphisms in India are
      substantially different from other populations and ethnic groups. Thus they
      signify an impact of ethnicity and provide a basis for future epidemiological and
      clinical studies.

PMID- 16436010
TI  - Obesity, breast cancer and the role of adipocytokines.
AB  - Obesity is a worldwide problem which impacts the risk and prognosis of some of
      the more common forms of cancer, including breast cancer in post-menopausal
      women. As the basis for understanding the potential mechanisms of obesity and
      cancer relationship has advanced, a number of new hypotheses have emerged. The
      adipocytokines are a complex group of biologically active polypeptides. Leptin is
      a growth hormone, secreted by adipose tissue, whose levels are normally elevated
      in obese individuals and may have a promoting effect on carcinogenesis and
      metastasis of breast cancer, possibly in an autocrine manner. Leptin interferes
      with the insulin signaling pathway and in type 2 diabetes plasma leptin levels
      are found to be correlated with the degree of insulin resistance, a relationship
      independent of body mass. This relationship might provide a mechanistic
      explanation for promotion potential.

PMID- 16436011
TI  - Diet and lifestyle intervention among patients with colorectal adenomas:
      rationale and design of a Malaysian study.
AB  - Comprehensive evaluation of the large body of consistent evidence from
      laboratory, epidemiologic and clinical studies has led to the conclusion that
      modification of the dietary and lifestyle patterns of populations has
      considerable potential for reducing cancer risk. This paper describes a
      randomized-controlled trial involving a diet and lifestyle intervention for
      patients with history of colorectal adenomas. The primary aim of this trial is to
      evaluate the effectiveness of the intervention with reference to recurrence of
      adenomatous polyps over a two year period--the first year being the intervention
      period and the second year of the study allowing for post-intervention follow-up.
      Subjects found to fit the inclusion criteria are recruited and randomized to two
      groups: the intervention group and the control group. The intervention group
      subjects will attend a monthly lecture-discussion session for 10 months and small
      group counseling on modification of lifestyle behavior and diet as well as
      receive educational materials which were adapted from the WCRF Diet and Health
      Recommendations for Cancer Prevention. Control subjects will be provided with the
      usual care given to such patients. One hundred and sixteen patients who were
      diagnosed with colorectal adenomatous polyps in the previous twelve months at the
      Hospital Kuala Lumpur have already been enrolled in this trial. Baseline data
      collection is on-going.

PMID- 16436012
TI  - Molecular structure of BRCA1-estrogen receptor alpha-estrogen complex: relevance
      to breast cancer?
AB  - Recent studies indicate that BRCA1, the first breast cancer susceptibility gene
      to be identified and cloned, interacts with and regulates the activity of
      estrogen receptor alpha. The availability of genetic tests for BRCA gene
      mutations has prompted cancer geneticists to generate information about genetic
      risk and inform women with a personal or family history of breast or ovarian
      cancer of preventive measures. However, knowledge on the human BRCA1-estrogen
      receptor alpha-estrogen complex is limited. Here, the author focuses on its 3D
      molecular structure and properties.

PMID- 16436013
TI  - Thyroid cancer with skull enlargement: a lesson learned?
AB  - A case of endemic goitre associated with thyroid cancer and huge enlargement of
      the scalp is reported in a Brazilian mulatto from an iodine deficient Central
      west region of the country. On admission, osteolytic metastases of follicular
      thyroid carcinoma were found scattered in the parietal bones. Impressive images
      from old files could illustrate and emphasize the hurdle-like role of poverty and
      inadequate social and cultural attitudes before the fight against cancer in
      regions with limited resources. Even in developed countries, goitres still occur
      in areas with iodine prophylaxis. Another concern is insufficiency of reliable
      data on the incidence and pattern of head and neck tumours in developing
      countries.

PMID- 16436015
TI  - The local clinical scientist, evidence-based practice, and personality
      assessment.
AB  - The local clinical scientist model was devised for clinical practitioners
      including those engaged in personality assessment. It emphasizes the importance
      of local data, the consideration of each clinical encounter as a mini-research
      project, and the incorporation of existing research data where relevant. It is
      consistent with, but goes beyond, evidence-based practice. There is a need to
      guard against the operation of cognitive heuristics for the model to be applied
      effectively.

PMID- 16436016
TI  - Unidimensionality and bandwidth in the Center for Epidemiologic Studies
      Depression (CES-D) Scale.
AB  - In this study, we compared classical test theory (CTT) and item response theory
      (IRT) approaches in analyzing the Center for Epidemiological Studies Depression
      (CES-D) Scale (Radloff, 1977). Standard item analyses, as well as Rasch (1960)
      analyses, both revealed item departures from unidimensionality in a sample of
      2,455 older persons responding to the CES-D. Positive affect items in the scale
      performed poorly overall, their removal reducing the scale's bandwidth only
      slightly. Modeling depression scores derived from Rasch measures and raw totals
      showed subtle but important differences for statistical inference. The assessment
      of depressive risk was slightly enhanced by using 16-item scale measures obtained
      from the results of the Rasch analysis as the dependent variable. Confirmatory
      factor analysis and parallel analysis verified the advantages of removing
      positively worded items. IRT and CTT techniques proved to be complementary in
      this study and can be usefully combined to improve measuring depression.

PMID- 16436017
TI  - Assessing personality change in psychotherapy with the SWAP-200: a case study.
AB  - Many studies document the efficacy of psychotherapy for acute syndromes such as
      depression, but less is known about personality change in patients treated for
      personality pathology. The Shedler-Westen Assessment Procedure (SWAP-200; Westen
      & Shedler, 1999a, 1999b) is an assessment tool that measures a broad spectrum of
      personality constructs and is designed to bridge the gap between the clinical and
      empirical traditions in personality assessment. In this article, we demonstrate
      the use of the SWAP-200 as a measure of change in a case study of a patient
      diagnosed with borderline personality disorder. We collected assessment data at
      the start of treatment and after 2 years of psychotherapy. The findings
      illustrate the personality processes targeted in intensive psychotherapy for
      borderline personality.

PMID- 16436018
TI  - The assessment of emotional intelligence: a comparison of performance-based and
      self-report methodologies.
AB  - We assessed the patterns of convergent validity for the Mayer-Salovey-Caruso
      Emotional Intelligence Test (Mayer, Salovey, & Caruso, 2002), a performance-based
      measure of emotional intelligence (EI) that entails presenting problems thought
      to have correct responses, and a self-report measure of EI (Schutte et al.,
      1998). The relations between EI and demographic characteristics of a diverse
      community sample (N = 223) concurred with previous research. However, the
      performance-based and self-report scales were not related to one another. Only
      self-reported EI scores showed a consistent pattern of relations with self
      reported coping styles and depressive affect, whereas the performance-based
      measure demonstrated stronger relations with age, education, and receiving
      psychotherapy. We discuss implications for the validity of these measures and
      their utility.

PMID- 16436019
TI  - Personality assessment training: view from a licensing board.
AB  - The literature contains numerous surveys about assessment training at the level
      of both doctoral programs and internships. There is minimal information about how
      such training is assessed by state and provincial regulatory bodies. In this
      article, we describe the process used by one state licensing board to assess a
      licensure candidate's transcript, conduct an oral examination, and potentially
      recommend remediation when the candidate is found to be deficient in specified
      skills. Our focus in this article is on the application of this evaluation
      process to personality assessment, although we also examined other areas of
      practice in a comparable manner.

PMID- 16436020
TI  - A short form of the Autonomy Scale: properties of the Autonomy-Connectedness
      Scale (ACS-30).
AB  - The Autonomy Scale (Bekker, 1993) measures individual differences in gender
      linked autonomy, a psychological condition resulting from the process of
      individuation and separation. The theoretical background of the concept is found
      in a combination of feminist, neoanalytical object relations theory and
      attachment theory. The 3 subscales are Self-Awareness, Sensitivity to Others, and
      Capacity for Managing New Situations. We report the development and properties of
      the Autonomy-Connectedness Scale (ACS-30), a shortened 30-item version of the
      Autonomy Scale. We present 2 studies. In the first study, we examined the
      structure of the scale as well as its validity and reliability. The second study
      was aimed at further validation by relating the ACS-30 to various indexes of
      psychopathology. Exploratory as well as confirmatory factor analyses provided
      support for a 3-factor structure that was identical to that of the original
      scale. The ACS-30 showed good internal consistency reliability and an expected
      pattern of convergent validity with personality and mental health variables. The
      psychometric properties of the ACS-30 suggest it can be used to assess gender
      linked autonomy. It also has the advantage of being more economical and simple as
      compared with the original 50-item version.

PMID- 16436021
TI  - Identity status measurement across contexts: variations in measurement structure
      and mean levels among White American, Hispanic American, and Swedish emerging
      adults.
AB  - We conducted this study to examine measurement equivalence and mean differences
      in identity status across 3 ethnic/cultural contexts: White American, Hispanic
      American, and Swedish. We used the Extended Objective Measure of Ego Identity
      Status II (EOM-EIS-II; Bennion & Adams, 1986), a commonly used instrument in the
      identity status literature. We conducted analyses to ascertain the extent to
      which the EOM-EIS-II functioned equivalently in 3 ethnically/culturally different
      samples. The internal structure of the measure was consistent across contexts.
      When we statistically controlled effects of age and gender, mean differences
      tended to be largely cross-cultural at the observed level of analysis but to be
      both cross-ethnic and cross-cultural at the latent level of analysis. This
      divergence in findings was found despite the limited age range represented in
      each of the samples. We therefore concluded that measurement error may have
      played a role in these differences and that data gathered using the EOM-EIS-II
      should be analyzed using latent variable methods. We discuss results in terms of
      using the EOM-EIS-II with diverse populations.

PMID- 16436022
TI  - Distinctions among agency, communion, and unmitigated agency and communion
      according to the interpersonal circumplex, Five-factor model, and social
      emotional correlates.
AB  - In this study, we examined common measures of agency (AG), communion (CM), and
      unmitigated agency (UA) and unmitigated communion (UC) using the interpersonal
      circumplex and Five-factor models (FFM) as conceptual frameworks. AG aligned with
      interpersonal dominance in circumplex space and related positively to
      conscientiousness and inversely to neuroticism. CM corresponded with
      interpersonal affiliation and related positively to conscientiousness. UA was
      consistent with hostile-dominance and related to lower conscientiousness and
      higher neuroticism. UC related to friendly submission but was not strongly
      represented in the circumplex and did not relate to the FFM. Each construct
      showed distinct social-emotional correlates. These findings support the
      convergent and divergent properties of the constructs but suggest that additional
      attention to the conceptual definition and measurement of UC is warranted.

PMID- 16436023
TI  - Correlates of the MMPI-2 restructured clinical (RC) scales in a college
      counseling setting.
AB  - We designed this study to identify empirical correlates on the MMPI-2 (Butcher et
      al., 2001) restructured clinical (RC) scales in a college counseling setting with
      a sample of 228 men and 522 women from a university-based psychological clinic.
      Participants were administered the MMPI-2 at intake and were rated by their
      therapists on a variety of variables including a 192-item Client Description
      Form. The findings indicate that the RC scales were generally most strongly
      correlated with conceptually relevant criteria and generally uncorrelated with
      conceptually nonrelevant criteria, which replicated findings of convergent and
      discriminant validity from previous studies. Follow-up analyses indicate that the
      RC scales have improved discriminant validity in comparison to the clinical
      scales and stronger convergent validity than a set of alternative MMPI-2
      measures.

PMID- 16436024
TI  - Using the multifaceted Rasch model to improve the TAT/PSE measure of need for
      achievement.
AB  - We used the Rasch (1980) model to develop new pictures for the Thematic
      Apperception Test (C. D. Morgan & Murray, 1938; McClelland, Atkinson, Clark, &
      Lowell, 1953) or picture story exercise to measure need for achievement (nAch).
      In Experiments 1 and 2, we analyzed stories to assess the difficulty level of a
      total of 8 pictures using the multifaceted Rasch model with picture difficulty,
      story probe difficulty, and participant ability as facets with a partial credit
      model (FACETS; Linacre, 2005). A total of 6 pictures were retained and 4 new ones
      added for Experiment 3 in which 201 participants wrote 6 stories to a random set
      of the 10 pictures. FACETS analysis revealed improved person separation
      reliability. In Experiment 4, 206 participants wrote 1 story to the Studying
      picture either before or after filling out a battery of achievement-related
      questionnaires. The 2 experimental groups did not differ in the amount of nAch in
      their stories. The coder facet was demonstrated with 2 independent coders using
      the revised coding system for nAch.

PMID- 16436027
TI  - Errata.

PMID- 16436028
TI  - The effects of visitor density and intensity on the behavior of two captive
      jaguars (Panthera onca).
AB  - Several researchers have reported significant effects of visitor density and
      intensity on captive animal behavior. This study determined whether this was the
      case for 2 captive jaguars housed at the Woodland Park Zoo, Seattle, WA. Subjects
      were monitored for changes in behavior as a function of visitor density and
      intensity. The jaguars were observed for 8 hr per week for 29 weeks--March 31
      until October 11, 1998--for a total of 230 hr. Continuous frequency sampling was
      used, and visitor density and intensity were recorded every minute. Parametric
      statistics were used to test for correlations between behavior and density,
      intensity, or a combination of the two. Both density and intensity were
      significant for time spent non-visible for both cats, and intensity showed a
      significant effect on the female's pacing behavior. In addition, the male cat
      exhibited a trend for increased aggression based on both visitor density and
      intensity and a trend of intensity affecting his social behavior. In conclusion,
      both density and intensity had a significant effect on behavior, with intensity
      showing a larger effect.

PMID- 16436029
TI  - Characteristics of owned dogs on the island of New Providence, The Bahamas.
AB  - This study reports the findings from street interviews on owned dogs (N = 442) in
      New Providence, The Bahamas. Many households kept dogs outside, and roughly 43%
      of households allowed at least 1 dog to roam. Dogs kept inside most likely were
      considered a companion, whereas dogs used for security were kept outside. With
      36.1% of the dog population neutered and 4.4 puppies per litter surviving to
      breeding age (6 months), the population continues to produce more dogs than are
      required just to maintain its numbers. Potcakes, the local mongrel, followed by
      pit bulls, were the most commonly kept dogs. Comparison with a study conducted in
      the Yucatan, Mexico (A. Ortega-Pacheco et al., 2005), suggests that the hostile
      subtropical environment of New Providence well may be responsible for checking
      the growth of the dog population. The study also suggests that until less than
      20% of the females breed, there will continue to be a dog problem on the island.

PMID- 16436030
TI  - Pain detection and amelioration in animals on the farm: issues and options.
AB  - Pain in nonhuman animals is a difficult concept to identify and measure. This
      article briefly describes the consequences of pain in animals on the farm and
      explains the reasons for the minimal use of analgesics in farmed animals. Pain
      can have implications for both animal welfare and economics. The reasons for a
      low use of analgesics in farmed animals include the lack of recognition of animal
      pain owing to the apparent lack of anthropomorphically identifiable behavioral
      changes, concern over human food safety, and lack of research efforts to develop
      safe analgesics for farm use. Treatment cost relative to the benefits expected is
      another hindering factor. Interventions to minimize pain must begin with
      developing objective and practical measures for pain identification and
      measurement at the farm level. A suggested use of a combination of different
      behavioral and physiological indicators would help to identify pain in animals.
      To facilitate continued usage of the methodologies on the farm it also is
      necessary to evaluate the economic implication of the pain alleviation
      intervention.

PMID- 16436031
TI  - Urinary corticosterone levels in mice in response to intraperitoneal injections
      with saline.
AB  - The concept of refinement is an important issue in the field of laboratory animal
      science. Refinement-based research aims to improve animal welfare, to increase
      the reliability of experimental outcome, and to diminish variation. In search of
      refinement of experimental techniques, this study investigated whether urinary
      corticosterone can be used as a noninvasive measure of acute stress in mice.

PMID- 16436032
TI  - The role of zoos in the rehabilitation of animals in the circus.
AB  - In 1998, the government of India enforced a ban on performance/exhibition of 5
      species of nonhuman animals: (a) lions, (b) tigers, (c) leopards, (d) bears, and
      (e) monkeys. The Ministry of Environment and Forests gave the responsibility to
      the Central Zoo Authority (CZA) for rehabilitation of these animals. Between 1999
      and 2001, the CZA created rescue centers for rehabilitation of lions and tigers
      in the off-display areas of 5 zoos: (a) Bangalore, (b) Chennai, (c)
      Vishakhapatnam, (d) Tirupathi, and (e) Jaipur. Today, the CZA has rehabilitated
      314 lions and tigers from circuses. The CZA has been meeting the expenses toward
      maintenance (feeding of and providing health care for) of the animals,
      outsourcing of staff, and maintaining enclosures. This article focuses on the
      mammoth work that the selected zoos had to carry out in rehabilitating the lions
      and tigers from the circuses.

PMID- 16436035
TI  - Cellular therapies for kidney failure.
AB  - Dialysis and transplantation of human kidneys represent effective therapies to
      replace kidney function, but each has limitations. Xenotransplantation of whole
      kidneys from non-primate donors is complicated by humoral and severe cellular
      rejection. The use of individual cells or groups of cells to regenerate or repair
      damaged tissue (cellular therapies) offers an alternative for renal replacement.
      Cellular strategies include: incorporation of new nephrons into the kidney;
      growing new kidneys in situ/renal organogenesis; use of embryonic or adult stem
      cells; and nuclear transplantation/therapeutic cloning. These approaches
      circumvent humoral rejection of xenogeneic tissue. Cellular rejection is
      ameliorated if embryonic cells are transplanted. It is likely that replacement of
      renal function via one or more cellular approach will constitute a part of future
      mainstream medical practice.

PMID- 16436036
TI  - Anti-TNF-alpha agents in the treatment of psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a potentially debilitating disease that may affect
      small and large peripheral joints, entheses and the axial skeleton. The different
      clinical manifestations of PsA have been accounted for by various proposals of
      subdividing the patients into different subgroups. According to the predominant
      clinical symptoms, most patients can be classified as belonging to the spectrum
      of spondyloarthritides (SpA) or rheumatoid arthritis (RA). The conventional
      therapeutic approach comprises non-steroidal anti-inflammatory drugs, systemic
      and intra-articular corticosteroids, and disease-modifying antirheumatic drugs
      such as sulfasalazine, methotrexate, ciclosporin and leflunomide. Similar to RA,
      recent trials in PsA have shown excellent results with the tumour necrosis factor
      (TNF) blockers etanercept, infliximab and adalimumab, which have positive effects
      not only on joints, but also on the skin when affected by psoriasis, quality of
      life, function and slowing of disease progress, as evidenced radiologically. Anti
      TNF therapy has been generally safe in clinical trials of PsA. Taken together,
      there has been definite recent progress in the treatment of PsA, especially for
      severely affected patients.

PMID- 16436037
TI  - G protein-coupled receptors in haematopoietic disruption.
AB  - Haematopoiesis is the process by which blood and immune cells are replenished
      from a finite number of resident bone marrow (BM) haematopoietic stem cells
      (HSCs). Regulatory molecules within the BM microenvironment contribute
      developmental signals to an interactive network capable of ensuring ordered
      biological processes. Many bioactive molecules contribute to the network through
      G protein-coupled receptors (GPCRs). GPCRs are seven-transmembrane receptors
      that, following ligand binding, signal by activating coupled heterotrimeric G
      proteins. This review focuses on those bioactive molecules that regulate
      haematopoietic development through GPCRs. Chemokines (SDF-1alpha, MIP-1), opioids
      and tachykinins (SP, NK-A) are important G protein-coupled haematopoietic
      regulators. Their biology in normal and diseased haematopoiesis is discussed
      below, as well as their potential as therapeutic targets.

PMID- 16436038
TI  - T regulatory cells and the control of allergic disease.
AB  - Allergic diseases are caused by the induction of T helper (Th)2 cells and IgE
      responses specific for common environmental antigens (allergens) in susceptible
      individuals. There is increasing interest in the role of both naturally occurring
      and induced regulatory T cell (Treg) populations in preventing these
      inappropriate immune responses and the underlying sensitisation to allergens.
      Current evidence suggests that Tregs may actively prevent Th2 responses to
      allergens occurring in healthy non-atopic individuals and that their function may
      be impaired in allergic patients. Evidence that existing therapies may act by
      modulating Treg function is reviewed. Future research aims to understand the
      mechanisms involved in the generation and function of allergen-specific Tregs. A
      primary aim is to promote the development of optimised therapeutic regimens with
      the capacity to provide long-lasting, allergen-specific, inhibitory mechanisms at
      the time and site of allergen challenge.

PMID- 16436039
TI  - Kunjin virus replicons: an RNA-based, non-cytopathic viral vector system for
      protein production, vaccine and gene therapy applications.
AB  - The application of viral vectors for gene expression and delivery is rapidly
      evolving, with several entering clinical trials. However, a number of issues,
      including safety, gene expression levels, cell selectivity and antivector
      immunity, are driving the search for new vector systems. A number of replicon
      based vectors derived from positive-strand RNA viruses have recently been
      developed, and this paper reviews the current knowledge on the first flavivirus
      replicon system, which is based on the Australian flavivirus Kunjin (KUN). Like
      most replicon systems, KUN replicons can be delivered as DNA, RNA or virus-like
      particles, they replicate their RNA in the cytoplasm and direct prolonged high
      level gene expression. However, unlike most alphavirus replicon systems, KUN
      replicons are non-cytopathic, with transfected cells able to divide, allowing the
      establishment of cell lines stably expressing replicon RNA and heterologous
      genes. As vaccine vectors KUN replicons can induce potent, long-lived,
      protective, immunogen-specific CD8+ T cell immunity, a feature potentially
      related to extended production of antigen and double-stranded RNA-induced 'danger
      signals'. The identification of KUN replicon mutants that induce increased levels
      of IFN-alpha/beta has also spawned investigation of KUN replicons for use in
      cancer gene therapy. The unique characteristics of KUN replicons may thus make
      them suitable for specific protein production, vaccine and gene therapy
      applications.

PMID- 16436040
TI  - The role of myostatin and bone morphogenetic proteins in muscular disorders.
AB  - Skeletal muscle is the largest organ in the human body, and plays an important
      role in body movement and metabolism. Skeletal muscle mass is lost in genetic
      disorders such as muscular dystrophy, muscle wasting and ageing. Chemicals and
      proteins that restore muscle mass and function are potential drugs that can
      improve human health and could be used in the clinic. Myostatin is a muscle
      specific member of the transforming growth factor (TGF)-beta superfamily that
      plays an essential role in the negative regulation of muscle growth. Inhibition
      of myostatin activity is a promising therapeutic method for restoring muscle mass
      and strength. Potential inhibitors of myostatin include follistatin domain
      containing proteins, myostatin propeptide, myostatin antibodies and chemical
      compounds. These inhibitors could be beneficial for the development of clinical
      drugs for the treatment of muscular disorders. Bone morphogenetic protein (BMP)
      plays a significant role in the development of neuromuscular architecture and its
      proper functions. Modulation of BMP activity could be beneficial for muscle
      function in muscular disorders. This review will describe the current progress in
      therapy for muscular disorders, emphasising the importance of myostatin as a drug
      target.

PMID- 16436041
TI  - Therapies for necrotising fasciitis.
AB  - Necrotising fasciitis is a rare but life-threatening infectious disease
      emergency. Delays in diagnosis and treatment are common, and mortality rates
      often exceed 30%. Successful management of this disease requires high clinical
      suspicion and aggressive action. The mainstays of therapy include early and wide
      surgical debridement, antibiotics and supportive care, with prompt surgical
      intervention. Adjunctive modalities, such as protein synthesis inhibitors,
      hyperbaric oxygen and intravenous immunoglobulin, may have a role, but their
      effectiveness remains unproven. New rapid diagnostic tools are emerging that
      promise to revolutionize early detection of necrotising fasciitis. Research into
      the molecular microbiology, especially regarding group A streptococcus, are
      providing novel insights into the pathogenesis of necrotising soft tissue
      infections and identifying future targets for rationally designed interventions.

PMID- 16436042
TI  - Use of recombinant human thyroid-stimulating hormone in the management of well
      differentiated thyroid cancer.
AB  - Recombinant human (rh) thyroid-stimulating hormone (TSH) has changed the care of
      patients with well-differentiated thyroid cancer (DTC). Traditionally, thyroid
      hormone withdrawal has been used to increase TSH concentrations for optimising
      trapping and retention of radioiodine for thyroid remnant ablation and for
      diagnostic procedures (measurement of thyroglobulin and whole body scan) used in
      the follow-up of patients with DTC. The resulting hypothyroidism is, however,
      accompanied by substantial morbidity. rhTSH is an effective and safe alternative
      to thyroid hormone withdrawal for follow-up of DTC. Its ability to detect
      persistent or recurrent disease is similar to that of thyroid hormone withdrawal.
      At the present time, rhTSH is approved for diagnostic monitoring of patients with
      DTC as well as for pretherapeutic stimulation in low-risk patients for remnant
      ablation with 100 mCi (131)I (in the EU). In addition, rhTSH has potential for
      use in facilitating the treatment of metastasis in patients with DTC and in
      patients with non-toxic nodular goiter; however, more clinical trials are needed
      to confirm its use in these situations.

PMID- 16436043
TI  - Ribosome display for improved biotherapeutic molecules.
AB  - Ribosome display presents an innovative in vitro technology for the rapid
      isolation and evolution of high-affinity peptides or proteins. Displayed proteins
      are bound to and recovered from target molecules in multiple rounds of selection
      in order to enrich for specific binding proteins. No transformation step is
      necessary, which could lead to a loss of library diversity. A cycle of display
      and selection can be performed in one day, enabling the existing gene repertoire
      to be rapidly scanned. Proteins isolated from the panning rounds can be further
      modified through random or directed molecular evolution for affinity maturation,
      as well as selected for characteristics such as protein stability, folding and
      functional activity. Recently, the field of display technologies has become more
      prominent due to the generation of new scaffolds for ribosome display, isolation
      of high-affinity human antibodies by phage display, and their implementation in
      the discovery of novel protein-protein interactions. Applications for this
      technology extend into the broad field of antibody engineering, proteomics, and
      synthetic enzymes for diagnostics and therapeutics in cancer, autoimmune and
      infectious diseases, neurodegenerative diseases and inflammatory disorders. This
      review highlights the role of ribosome display in drug discovery, discusses
      advantages and disadvantages of the system, and attempts to predict the future
      impact of ribosome display technology on the development of novel engineered
      biopharmaceutical products for biological therapies.

PMID- 16436047
TI  - The archaeal Hjm helicase has recQ-like functions, and may be involved in repair
      of stalled replication fork.
AB  - The archaeal Hjm is a structure-specific DNA helicase, which was originally
      identified in the hyperthermophilic archaeon, Pyrococcus furiosus, by in vitro
      screening for Holliday junction migration activity. Further biochemical analyses
      of the Hjm protein from P. furiosus showed that this protein preferably binds to
      fork-related Y-structured DNAs and unwinds their double-stranded regions in
      vitro, just like the E. coli RecQ protein. Furthermore, genetic analyses showed
      that Hjm produced in E. coli cells partially complemented the defect of functions
      of RecQ in a recQ mutant E. coli strain. These results suggest that Hjm may be a
      functional counterpart of RecQ in Archaea, in which it is necessary for the
      maintenance of genome integrity, although the amino acid sequences are not
      conserved. The functional interaction of Hjm with PCNA for its helicase activity
      further suggests that the Hjm works at stalled replication forks, as a member of
      the reconstituted replisomes to restart replication.

PMID- 16436048
TI  - Role of DNA polymerase theta in tolerance of endogenous and exogenous DNA damage
      in mouse B cells.
AB  - DNA polymerase theta (Poltheta) is a family A polymerase that contains an
      intrinsic helicase domain. To investigate the function of Poltheta in mammalian
      cells, we have inactivated its polymerase activity in CH12 mouse B lymphoma cells
      by targeted deletion of the polymerase core domain that contains the catalytic
      aspartic acid residue. Compared to parental CH12 cells, mutant cells devoid of
      Poltheta polymerase activity exhibited a slightly reduced growth rate,
      accompanied by increased spontaneous cell death. In addition, mutant cells showed
      elevated sensitivity to mitomycin C, cisplatin, etoposide, gamma-irradiation and
      ultraviolet (UV) radiation. Interestingly, mutant cells were more sensitive to
      the alkylating agent methyl methanesulfonate (MMS) than parental cells. This
      elevated MMS sensitivity relative to WT cells persisted in the presence of
      methoxyamine, an inhibitor of the major base excision repair (BER) pathway,
      suggesting that Poltheta is involved in tolerance of MMS through a mechanism that
      appears to be different from BER. These results reveal an important role for
      Poltheta in preventing spontaneous cell death and in tolerance of not only DNA
      interstrand cross-links and double strand breaks but also UV adducts and
      alkylation damage in mammalian lymphocytes.

PMID- 16436049
TI  - Gene order in human alpha-globin locus is required for their temporal specific
      expressions.
AB  - The human alpha-globin cluster represents a unique model of transcriptional
      regulation and provides challenges to the current understanding of interactions
      between distal and proximal regulatory elements. Although the gene proximal
      regions are believed to possess almost all the necessary elements for temporal
      and spatial specificity of gene transcription, it is still not clear whether the
      relative distance of embryonic zeta- and fetal/adult alpha-genes to their distal
      regulatory element alpha-URE plays any role in transcriptional switching. To
      investigate the role of gene order in regulating temporal expression, we inverted
      the entire structure gene region of human alpha-globin locus in a BAC clone
      bringing alpha-genes closest to alpha-URE and zeta-gene the farthest away.
      Expression analysis of the reverted locus in transgenic mice showed that alpha
      globin genes, now relocated closer to alpha-URE, maintained their expression
      levels through all developmental stages. However, the zeta-globin gene suffered a
      total loss at both embryonic and fetal/adult stages. It indicates that proximal
      location of zeta-globin gene to alpha-URE is necessary for its normal embryonic
      expression and necessary to prevent embryonic expression of the alpha-globin
      gene. We proved that, in the human alpha-globin gene cluster, the normal order of
      structural genes relative to alpha-URE plays a crucial role in the regulation of
      developmental switching.

PMID- 16436046
TI  - Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury
      and preconditioning: implications for pathology and cardioprotection.
AB  - The mechanisms of mitochondrial proton (H+) leak under various pathophysiological
      conditions are poorly understood. In the present study it was hypothesized that
      different mechanisms underlie H+ leak in cardiac IR (ischaemia/reperfusion)
      injury and IPC (ischaemic preconditioning). Potential H(+) leak mechanisms
      examined were UCPs (uncoupling proteins), allosteric activation of the ANT
      (adenine nucleotide translocase) by AMP, or the PT (permeability transition)
      pore. Mitochondria isolated from perfused rat hearts that were subjected to IPC
      exhibited a greater H+ leak than did controls (202+/-27%, P<0.005), and this
      increased leakage was completely abolished by the UCP inhibitor, GDP, or the ANT
      inhibitor, CAT (carboxyattractyloside). Mitochondria from hearts subjected to IR
      injury exhibited a much greater amount of H+ leak than did controls (411+/-28%,
      P<0.001). The increased leakage after IR was weakly inhibited by GDP, but was
      inhibited, >50%, by carboxyattractyloside. In addition, it was inhibited by
      cardioprotective treatment strategies including pre-IR perfusion with the PT pore
      inhibitors cyclosporin A or sanglifehrin A, the adenylate kinase inhibitor, AP5A
      (diadenosine pentaphosphate), or IPC. Together these data suggest that the small
      increase in H+ leak in IPC is mediated by UCPs, while the large increase in H+
      leak in IR is mediated by the ANT. Furthermore, under all conditions studied, in
      situ myocardial O2 efficiency was correlated with isolated mitochondrial H+ leak
      (r2=0.71). In conclusion, these data suggest that the modulation of H+ leak may
      have important implications for the outcome of IR injury.

PMID- 16436050
TI  - The N-terminal hydrophobic sequence of autotaxin (ENPP2) functions as a signal
      peptide.
AB  - Autotaxin, also known as ENPP2, was originally isolated from the culture medium
      of melanoma cells as a cell-motility promoting protein. It regulates cell growth,
      motility, and angiogenesis through the production of lysophosphatidic acid and
      sphingosine 1-phosphate. Because autotaxin shows overall structural similarity to
      the well-characterized PC-1, it has been assumed to be a type II transmembrane
      protein that is expressed on the cell surface and is released into the
      extracellular space after proteolytic cleavage. We found, however, that while
      autotaxin was efficiently secreted into the extracellular space both in vitro and
      in vivo, it was expressed neither on the surfaces of autotaxin-transfected cells
      nor on those of the autotaxin-expressing choroid plexus epithelium cells. N
      terminal sequencing of the secreted autotaxin revealed that it was cleaved at two
      N-terminal sites that match the consensus sequences for cleavage by a signal
      peptidase and furin. In addition, when translated in vitro, autotaxin was co
      translationally translocated into microsome membranes, and its N-terminal 3-kDa
      fragment corresponding to a signal sequence was cleaved. These data demonstrate
      that the N-terminal hydrophobic sequence of autotaxin functions as a signal
      peptide, not as a transmembrane segment, and thus autotaxin is synthesized as a
      secreted protein.

PMID- 16436051
TI  - Dok-3 sequesters Grb2 and inhibits the Ras-Erk pathway downstream of protein
      tyrosine kinases.
AB  - Adaptor proteins are essential in coordinating recruitment and, in a few cases,
      restraint of various effectors during cellular signaling. Dok-1, Dok-2 and Dok-3
      comprise a closely related family of adaptor, which negatively regulates mitogen
      activated protein kinase Erk downstream of protein-tyrosine kinases (PTKs).
      Recruitment of p120 rasGAP, a potent inhibitor of Ras, by Dok-1 and Dok-2 appears
      critical in the negative regulation of the Ras-Erk pathway. However, as Dok-3
      does not bind rasGAP, it has been unclear how Dok-3 inhibits Erk downstream of
      PTKs. Here, we identified Grb2 as a Dok-3-binding protein upon its tyrosine
      phosphorylation. This interaction required the intact binding motifs of the Grb2
      SH2 domain, and a mutant (Dok-3-FF) having a Tyr/Phe substitution at these motifs
      failed to inhibit Ras and Erk activation downstream of a cytoplasmic PTK Src.
      Because Grb2 forms a stable complex with Sos, a crucial activator of Ras, these
      data suggest that Dok-3 restrains Grb2 and inhibits the ability of the Grb2-Sos
      complex to activate Ras. Indeed, forced expression of Dok-3, but not Dok-3-FF,
      inhibited the recruitment of the Grb2-Sos complex to Shc downstream of Src, which
      is an essential event for activation of the Ras-Erk pathway. These findings
      indicate that Dok-3 sequesters Grb2 from Shc and inhibits the Ras-Erk pathway
      downstream of PTKs.

PMID- 16436052
TI  - Chromatin assembly factor 1 ensures the stable maintenance of silent chromatin
      states in Arabidopsis.
AB  - Newly synthesized DNA is rapidly assembled into mature nucleosomes by the
      deposition of pre-existing and nascent histones, and some parts of this process
      are facilitated by chromatin assembly factor 1 (CAF-1). Loss-of-function mutants
      of CAF-1 in Arabidopsis, fasciata (fas), show a variety of morphological
      abnormalities and unique defects in gene expression in the meristems. In order to
      clarify the implications of CAF-1 in the maintenance of chromatin states in
      higher eukaryotes, we investigated transcriptional gene silencing (TGS) of
      various genes in fas mutants. Here, we show that TGS of endogenous CACTA
      transposons was released in a stochastic manner in fas. Other endogenous silent
      genes, a transposon AtMu1 and a hypothetical gene T5L23.26 at a heterochromatin
      knob, were also transcriptionally activated, and the activation of the three
      different silent loci at different chromosomal sites occurred non-concomitantly
      with each other. Furthermore, TGS of the silent beta-glucuronidase (GUS)
      transgene was also de-repressed randomly in fas. We conclude that CAF-1 ensures
      the stable inheritance of epigenetic states through growth and development in
      Arabidopsis.

PMID- 16436053
TI  - Odd-skipped related 2 gene transcription is regulated by CCAAT enhancer-binding
      protein delta in mesenchymal C3H10T1/2 cells.
AB  - Odd-skipped related 2 (Osr2) gene is mouse homolog of Drosophila Odd-skipped gene
      involved with the pair-rule segmentation phenotype in Drosophila mutant embryos.
      In this study, to examine Osr2 expression regulation, the mouse Osr2 promoter
      region was cloned and characterized, and found to have two enhancer elements in
      the -1463/-1031 (distal) and -581/+3 (proximal) regions, and a repressor region (
      4845/-1463, far distal). CCAAT/enhancer binding protein (C/EBP) binding sites
      were found in both the distal and proximal enhancer elements. Osr2 promoter
      activity was enhanced by C/EBPdelta, a member of the C/EBP family, in a dose
      dependent manner. Electrophoresis mobility shift assays showed that purified GST
      C/EBPdelta bound to distal (-1295/-1261) and proximal (-89/-55) C/EBP binding
      motifs. Chromatin immunoprecipitation demonstrated that acetylated histones H3,
      H4, and C/EBPdelta in the proximal region (-280/-43), but not the distal region (
      1438/-1196), indicating that the Osr2 promoter proximal region was
      transcriptionally activated in C3H10T1/2 cells. Our results suggest that Osr2
      expression is regulated by C/EBP regulatory elements.

PMID- 16436054
TI  - Human T-cell leukemia virus type-I oncoprotein Tax inhibits Fas-mediated
      apoptosis by inducing cellular FLIP through activation of NF-kappaB.
AB  - Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell
      leukemia and induces autoimmune disease. Previous analyses of tax transgenic mice
      suggested that protection of peripheral T-cells from Fas-mediated apoptosis by
      virus-encoded oncoprotein Tax was relevant to the onset of HTLV-I-induced
      diseases. Here, we show the high level expression of cellular FLICE/caspase-8
      inhibitory protein (c-FLIP) in Tax-expressing HTLV-I-infected T-cells. The
      silencing of c-FLIP expression by a lentivirus-based RNA interference system
      rendered Tax-positive HTLV-I-infected T-cells sensitive to Fas-mediated
      apoptosis. Exogenously expressed Tax by using a conditional Cre-loxP-mediated
      inducible system also inhibited Fas-mediated apoptosis by up-regulating c-FLIP
      expression in HTLV-I-negative T-cells. Tax mutant d3 which cannot activate
      CREB/ATF1, while another M22 mutant which cannot activate NF-kappaB did not,
      suppressed Fas-mediated apoptosis by inducing c-FLIP expression. Furthermore,
      expression of the dominant negative mutant of either NF-kappaB or IkappaBalpha
      canceled not only c-FLIP expression but also inhibitory activity against Fas
      mediated apoptosis by Tax. Inactivation of NFAT, however, did not decrease the
      expression of c-FLIP in HTLV-I-infected T-cells. Taken together, Tax inhibits Fas
      mediated apoptosis by up-regulating c-FLIP expression in HTLV-I-infected cells,
      and NF-kappaB activity plays an essential role in the up-regulation of c-FLIP.

PMID- 16436055
TI  - Strain typing with ISLpl1 in lactobacilli.
AB  - Twenty-seven Lactobacillus plantarum ssp. plantarum, 11 Lactobacillus
      paraplantarum and five Lactobacillus casei-related strains, isolated from various
      autochthonous Serbian and Montenegro-fermented foods, were identified using
      phenotypical characterization and current PCR methods based on PCR of the recA
      gene or the 23S-5S rRNA gene intragenic spacer (IS) region. The strains were
      genotypically characterized by a new method based on the insertion sequence
      element ISLpl11 that grouped these lactobacilli into 10 IS-fingerprinting groups.
      Between six and 23 copies of the ISLpl1 were found in each strain and the ISLpl1
      fingerprint groups correlated well with the origin of the strains. The method
      proved suitable for strain typing of lactic acid bacteria at the infraspecies
      level.

PMID- 16436056
TI  - Biofilms of clinical strains of Staphylococcus that do not contain polysaccharide
      intercellular adhesin.
AB  - Staphylococcus aureus and coagulase-negative staphylococci, primarily
      Staphylococcus epidermidis, are recognized as a major cause of nosocomial
      infections associated with the use of implanted medical devices. The capacity of
      S. epidermidis to form biofilms, allowing it to evade host immune defence
      mechanisms and antibiotic therapy, is considered to be crucial in colonizing the
      surfaces of medical implants and dissemination of infection. It has previously
      been demonstrated that the biofilm of a model strain S. epidermidis RP62A
      comprises two carbohydrate-containing moieties, a polysaccharide having a
      structure of a linear poly-N-acetyl-(1-->6)-beta-D-glucosamine and teichoic acid.
      In the present paper we show that, unlike this model strain, certain clinical
      isolates of coagulase-negative staphylococci produce biofilms that do not contain
      detectable amounts of poly-N-acetyl-(1-->6)-beta-D-glucosamine. In contrast to
      that of S. epidermidis RP62A, these biofilms are not detached with metaperiodate,
      while proteinase K causes their partial dispersal.

PMID- 16436057
TI  - Cloning and molecular characterization of Penicillium expansum genes upregulated
      under conditions permissive for patulin biosynthesis.
AB  - Penicillium expansum is commonly associated with patulin production in pomaceous
      fruits. Both the full-length isoepoxydon dehydrogenase (idh) gene and a 470 bp
      fragment of the 6-methylsalicylic acid synthase (6-msas) gene have been cloned
      from P. expansum. In addition, we cloned a 715 bp fragment of a putative ATP
      binding cassette transporter gene peab1, together with part of two putative
      cytochrome P450 monooxygenase genes P-450 1 and P-450 2. Increased expression of
      all five genes was observed under patulin-permissive conditions, indicating not
      only their likely involvement in patulin biosynthesis but indicating for the
      first time that regulation of patulin biosynthesis in P. expansum is mediated at
      the level of gene transcription.

PMID- 16436058
TI  - Proteomic analysis of the bacteriocin thuricin 17 produced by Bacillus
      thuringiensis NEB17.
AB  - Thuricin 17 is a recently discovered bacteriocin produced by Bacillus
      thuringiensis NEB17. The objective of this work was to conduct a proteomic
      analysis of this bacteriocin. The partial N- and C-terminal amino-acid sequences
      of thuricin 17 have now been determined using the Edman degradation and matrix
      assisted laser desorption ionization-quadrapole time of flight mass spectrometry
      (MS)/MS. A hydrophobic cluster analysis indicates that thuricin 17 contains a
      hydrophobic region, potentially corresponding to a membrane associated domain.
      Based on time of production, this bacteriocin may be produced as a secondary
      metabolite. Interestingly, thuricin 17 shares the same N-terminal sequence,
      DWTXWSXL, with a previously reported bacteriocin, Bacthuricin F4, produced by B.
      thuringiensis ssp. kurstaki strain BUPM4. This is the first time two bacteriocins
      from different Bacillus species have been shown to share similar N-terminal
      sequences.

PMID- 16436059
TI  - Effects of sterol biosynthesis inhibitors on endosymbiont-bearing
      trypanosomatids.
AB  - Some protozoa of the Trypanosomatidae family have a close relationship with an
      endosymbiotic bacterium. As the prokaryote envelope has a controversial origin, a
      sterol 24-methyltransferase inhibitor (20-piperidin-2-yl-5alpha-pregnan-3beta,20
      diol; 22,26-azasterol) was used as a tool to investigate lipid biosynthetic
      pathways in Crithidia deanei, an endosymbiont-bearing trypanosomatid. Apart from
      antiproliferative effects, this drug induced ultrastructural alterations,
      consisting of myelin-like figures in the cytoplasm and endosymbiont envelope
      vesiculation. Concurrently, a dramatic reduction of 24-alkyl sterols was observed
      after 22,26-azasterol treatment, both in whole cell homogenates, as well as in
      isolated mitochondria. These effects were associated with changes of phospholipid
      composition, in particular a reduction of the phosphatidylcholine content and a
      concomitant increase in phosphatidylethanolamine levels. Lipid analyses of
      purified endosymbionts indicated a complete absence of sterols, and their
      phospholipid composition was different from that of mitochondria or whole
      protozoa, being similar to eubacteria closely associated with eukaryotes.

PMID- 16436060
TI  - Yersinia pestis lacZ expresses a beta-galactosidase with low enzymatic activity.
AB  - Although very little, if any, beta-galactosidase activity is detected in Yersinia
      pestis by a standard Miller assay, we found that Y. pestis KIM6+ cells formed
      blue colonies on plates containing 5-bromo-4-chloro-3-indolyl-beta-D-galactoside
      (X-gal). Searches of the Y. pestis genome databases revealed the presence of
      noncontiguous sequences highly homologous to Escherichia coli lacZ, lacY, and
      lacI. Yersinia pestis lacZ is predicted to encode a 1060 amino-acid protein with
      62% identity and 72% similarity to beta-galactosidase from E. coli. A deletion in
      the Y. pestis lacZ gene caused the formation of white colonies on X-gal
      containing plates and beta-galactosidase activity was at background levels in the
      KIM6+lacZ mutant, while the complemented strain expressed about 190 Miller units.
      The Y. pestis lacZ promoter was not regulated by isopropylthiogalactoside or
      glucose. Finally, uptake of lactose by Y. pestis may be impaired.

PMID- 16436061
TI  - Sugarcane cellulose utilization by a defined microbial consortium.
AB  - Microorganisms isolated from diverse environmental sources were initially
      screened for carboxymethylcellulase activity. Nine strains that grew at elevated
      temperatures and which presented the highest activity were characterized further.
      Culture supernatants were assayed for potentiation of the enzymatic activity and,
      based on these results, consortia of four or nine microorganisms were tested for
      their capacity to grow on, and degrade a sugarcane leaf substrate. As predicted
      by the supernatant mixes, both consortia assayed were capable of degrading the
      cellulosic substrate provided. The group comprising of four strains was as
      efficient as the mix of all nine strains.

PMID- 16436062
TI  - Clusters of diverse genes existing as multiple, sequence-variable mosaics in a
      phytoplasma genome.
AB  - Phytoplasmas are cell wall-less prokaryotes living as obligate parasites and
      pathogens of plants and insects, making them attractive subjects for studies to
      gain a greater understanding of transkingdom parasitism and pathogenicity. During
      a study of two phytoplasma genomes, we obtained evidence for previously
      unreported clustering of genes, pseudogenes, mobile genetic elements, intergenic
      repeat units, and repetitive extragenic palindromes that occur in multiple,
      homologous clusters in some phytoplasma genomes. The clusters represent
      previously unrecognized mosaics, possibly assembled through multiple events of
      targeted mobile element attack, duplication, recombination, and rearrangement.
      Multiple clusters could conceivably afford potential for genome reduction through
      homologous recombination. Differences in the sizes and multiplicity of such
      clusters possibly account for some of the previously reported but unexplained
      variations in genome size among closely related phytoplasma strains.

PMID- 16436063
TI  - Rapid detection of a chromosomally mediated penicillin resistance-associated ponA
      mutation in Neisseria gonorrhoeae using a real-time PCR assay.
AB  - The recent emergence of a decreased susceptibility of Neisseria gonorrhoeae
      strains to penicillin in New Caledonia has lead clinicians to operate a change in
      the treatment strategy. In addition, this important health issue has emphasized
      the need for a rapid means of detecting penicillin resistance in N. gonorrhoeae
      in order to select an effective treatment and limit the spread of resistant
      strains. In recent years, the use of fluorescence resonance energy transfer on
      the LightCycler has proven to be a valuable tool for the screening of mutations
      occurring in the genome of various microorganisms. In this study, we developed a
      real-time PCR assay coupled with a fluorometric hybridization probes system to
      detect a penicillin resistance-associated mutation on the N. gonorrhoeae ponA
      gene. Following an extensive evaluation involving 136 isolates, melting curve
      analysis correctly evidenced a 5 degrees C T(m) shift in all N. gonorrhoeae
      strains possessing this mutation, as determined by conventional sequencing
      analysis. Moreover, the mutation profiles obtained with the real-time PCR showed
      good correlation with the pattern of penicillin susceptibility generated with
      classical antibiograms. Overall, our molecular assay allowed an accurate and
      reproducible determination of the susceptibility to penicillin corresponding to a
      mutation present in all chromosomally mediated resistant strains of N.
      gonorrhoeae.

PMID- 16436064
TI  - Differences in the API 20E biochemical patterns of clinical and environmental
      Vibrio parahaemolyticus isolates.
AB  - Genetic differences in clinical and environmental strains of Vibrio
      parahaemolyticus have been widely used as criteria in identifying pathogenic
      isolates. However, few studies have been carried out to assess the differences in
      biochemical characteristics of V. parahaemolyticus isolates from human and
      environmental sources. We compared the biochemical profiles obtained by the
      characterization of V. parahaemolyticus isolates from human infections and the
      marine environment using the API 20E system. Environmental and clinical isolates
      showed significant differences in the gelatin and arabinose tests. Additionally,
      clinical isolates were correctly identified according to the API 20E profile
      using 0.85% NaCl diluent, but they presented nonspecific profiles with 2% NaCl
      diluent. In contrast, use of 2% NaCl diluent facilitated correct identification
      of the environmental isolates. Clinical isolates showed significant differences
      in up to five biochemical tests with respect to the API 20E database. The API 20E
      system is widely used in routine identification of bacteria in clinical
      laboratories, and this discrepancy in an important number of biochemical tests
      may lead to misidentification of V. parahaemolyticus infection.

PMID- 16436065
TI  - Development of a rapid and simple Agrobacterium tumefaciens-mediated
      transformation system for the fungal pathogen Heterobasidion annosum.
AB  - Heterobasidion annosum causes root and butt-rot in trees and is the most serious
      forest pathogen in the northern hemisphere. We developed a rapid and simple
      Agrobacterium-mediated method of gene delivery into H. annosum to be used in
      functional studies of candidate genes and for visualization of mycelial
      interactions. Heterobasidion annosum TC 32-1 was cocultivated at pH 5.6 and 20
      degrees C in Hagems medium with Agrobacterium tumefaciens C58 carrying plasmids
      with hygromycin B resistance as the selectable marker and green fluorescent
      protein as a visual marker. We obtained 18 mitotically stable transformed
      isolates showing green fluorescence protein activity.

PMID- 16436066
TI  - A Na+/H+ antiporter gene of the moderately halophilic bacterium Halobacillus
      dabanensis D-8T: cloning and molecular characterization.
AB  - A gene encoding a Na(+)/H(+) antiporter was cloned from a chromosomal DNA of
      Halobacillus dabanensis strain D-8(T) by functional complementation. Its presence
      enabled the antiporter-deficient Escherichia coli strain KNabc to survive in the
      presence of 0.2 M NaCl or 5 mM LiCl. The gene was sequenced and designated as
      nhaH. The deduced amino-acid sequence of NhaH consists of 403 residues with a
      calculated molecular mass of 43,481 Da, which was 54% identical and 76% similar
      to the NhaG Na(+)/H(+) antiporter of Bacillus subtilis. The hydropathy profile
      was characteristic of a membrane protein with 12 putative transmembrane domains.
      Everted membrane vesicles prepared from E. coli cells carrying nhaH exhibited
      Na(+)/H(+) as well as Li(+)/H(+) antiporter activity, which was pH-dependent with
      highest activities at pH 8.5-9.0 and at pH 8.5, respectively. Moreover, nhaH
      confers upon E. coli KNabc cells the ability to grow under alkaline conditions.

PMID- 16436067
TI  - Pythium litorale sp. nov., a new species from the littoral of Lake Constance,
      Germany.
AB  - A description is given of Pythium litorale sp. nov., a new species from reed
      stands in Germany. Pythium litorale was among the most abundant species when the
      oomycete community of littoral soils of Lake Constance was studied. It was
      consistently isolated from flooded as well as from drier reed sites. The species
      is characterized by subglobose, papillate and internally proliferating sporangia,
      globose hyphal swellings, the absence of oogonia in single culture and a high
      optimum growth temperature. It proved to be nonpathogenic to Phragmites
      australis, the predominating plant in the investigated sites. Molecular analysis
      of ribosomal DNA internal transcribed spacer regions placed Pythium litorale in a
      clade together with its closest relatives Pythium megacarpum, Pythium boreale,
      Pythium montanum and Pythium carbonicum. The generic status of this basal clade
      in Pythium is currently under discussion, as it possibly represents a separate
      genus that is distinct from Pythium, and shares several characteristics with
      Phytophthora.

PMID- 16436069
TI  - Isolation and characterization of Halomonas sp. strain IMPC, a p-coumaric acid
      metabolizing bacterium that decarboxylates other cinnamic acids under hypersaline
      conditions.
AB  - A moderately halophilic, mesophilic, Gram-negative, motile, nonsporulating
      bacterium, designated strain IMPC, was isolated from a table-olive fermentation
      rich in aromatic compounds, after enrichment on p-coumaric acid under halophilic
      conditions. Strain IMPC was able to degrade p-coumaric acid. p
      hydroxybenzaldehyde and p-hydroxybenzoic acid were detected as breakdown products
      from p-coumaric acid. Protocatechuic acid was identified as the final aromatic
      product of p-coumaric acid catabolism before ring fission. Strain IMPC
      transformed various cinnamic acids with substituent H, OH, CH(3) or OCH(3) in the
      para- and/or meta-position of the aromatic ring to the corresponding benzoic
      acids, indicating a specific selection. A beta-oxidation pathway was proposed for
      these transformations. Phylogenetic analysis of the 16S rRNA gene revealed that
      this isolate was a member of the genus Halomonas. Strain IMPC was closely related
      to Halomonas elongata ATCC 33173(T)and Halomonas eurihalina ATCC 49336(T).

PMID- 16436068
TI  - Computational identification of BioR, a transcriptional regulator of biotin
      metabolism in Alphaproteobacteria, and of its binding signal.
AB  - Comparative genomic analysis was applied to identify the biotin transcriptional
      regulator, BioR, in most Alphaproteobacteria, and to identify its recognition
      signal TTATMKATAA. BioR belongs to the GntR family of transcriptional repressors.
      The functional assignment is supported by three lines of evidence: (1) bioR is
      positionally clustered with various bio genes, both for biotin biosynthesis and
      transport; (2) in most cases, candidate BioR-binding sites (BIOR boxes) are
      observed upstream of the bioR genes, suggesting autoregulation; (3) the phyletic
      distribution of the BIOR boxes coincides exactly with the phyletic distribution
      of the bioR genes, as the genomes lacking BIOR boxes do not have orthologs of
      bioR. Thus, in Alphaproteobacteria, BioR seems to have assumed the role of the
      biotin regulator that in most other bacteria is fulfilled by the dual function
      biotin-protein ligase BirA having the DNA-binding helix-turn-helix domain.

PMID- 16436070
TI  - Horizontal transfer of nonconjugative plasmids in a colony biofilm of Escherichia
      coli.
AB  - We tested the possibility of nonconjugative lateral DNA transfer in a colony
      biofilm of mixed Escherichia coli strains. By simply coculturing a plasmid-free
      F(-) strain and another F(-) strain harboring a nonconjugative plasmid in a
      colony biofilm on antibiotic-free agar media, transformed cells were produced
      within 24-48 h at the frequency of 10(-10)-10(-9) per recipient cell. PCR
      analysis of the transformed cells demonstrated the occurrence of lateral plasmid
      transfer. These cells survived until at least day 7 under antibiotic-free
      conditions. Liquid cultures of the same strains in Luria-Bertani broth produced
      no or few transformants, suggesting the importance of colony-biofilm formation
      for plasmid transfer. This is a novel line of evidence indicating that
      nonconjugative, nonviral horizontal gene transfer can occur between E. coli
      cells.

PMID- 16436071
TI  - Substrate specificity of nonribosomal peptide synthetase modules responsible for
      the biosynthesis of the oligopeptide moiety of cephabacin in Lysobacter
      lactamgenus.
AB  - Lysobacter lactamgenus produces cephabacins, a class of beta-lactam antibiotics
      which have an oligopeptide moiety attached to the cephem ring at the C-3
      position. The nonribosomal peptide synthetase (NRPS) system, which comprises four
      distinct modules, is required for the biosynthesis of this short oligopeptide,
      when one takes the chemical structure of these antibiotics into consideration.
      The cpbI gene, which has been identified in a region upstream of the pcbAB gene,
      encodes the NRPS - polyketide synthase hybrid complex, where NRPS is composed of
      three modules, while the cpbK gene -- which has been reported as being upstream
      of cpbI-- comprises a single NRPS module. An in silico protein analysis was able
      to partially reveal the specificity of each module. The four recombinant
      adenylation (A) domains from each NRPS module were heterologously expressed in
      Escherichia coli and purified. Biochemical data from ATP-PPi exchange assays
      indicated that L-arginine was an effective substrate for the A1 domain, while the
      A2, A3 and A4 domains activated L-alanine. These findings are in an agreement
      with the known chemical structure of cephabacins, as well as with the anticipated
      substrate specificity of the NRPS modules in CpbI and CpbK, which are involved in
      the assembly of the tetrapeptide at the C-3 position.

PMID- 16436072
TI  - Detecting single nucleotide polymorphisms using DNA arrays for plant pathogen
      diagnosis.
AB  - The lack of a rapid and reliable means for routine pathogen identification has
      been one of the main limitations in plant disease management, and has pushed the
      development of culture-independent, molecular approaches. Currently, DNA array
      technology is the most suitable technique for high-throughput detection and
      identification, as well as quantification, of multiple pathogens in a single
      assay. Closely related pathogens that may have completely different host ranges
      or pathogenicity often differ in only a single to a few base pairs in genes that
      may be targeted for identification. Therefore, the ability to discriminate single
      nucleotide polymorphisms (SNPs) should be pursued in any diagnostic assay. In
      this paper, we demonstrate the utility of DNA array technology to detect SNPs
      while accounting for specific criteria such as the position of the mismatch, the
      sequence of the oligonucleotide, and the length and amount of labeled amplicons
      that are hybridized. When disregarding mismatches at the extreme ends of the
      oligonucleotides, cross hybridization to single mismatch oligonucleotides is rare
      when processing environmental samples that contain genetic material from unknown
      sources. In addition to plant pathology, this study is relevant for any field of
      research where DNA arrays are used to detect mutations or polymorphisms, ranging
      from human diagnostics to environmental microbiology and microbial ecology.

PMID- 16436073
TI  - A recombinant Mycobacterium tuberculosis in vitro transcription system.
AB  - In vitro transcription constitutes an important tool in the study of the
      regulation of gene expression. Here, we present a fast and easy procedure to
      prepare Mycobacterium tuberculosis RNA polymerase for in vitro transcription
      assays. RNA polymerase is assembled from recombinant proteins expressed in
      Escherichia coli, thus eliminating the need for biosafety containment facilities,
      and is mixed with any of the 13 M. tuberculosissigma factors. We show that the
      recombinant RNA polymerase is free from contaminating sigma factors, produces
      transcriptional start sites matching those characterized in vivo and allows the
      formal identification of sigma factors involved in the expression of genes of
      interest.

PMID- 16436074
TI  - Multiple phases of competence occur during the Helicobacter pylori growth cycle.
AB  - The gastric pathogen Helicobacter pylori undergoes genetic exchange at unusually
      high frequencies, primarily through natural transformation. Despite progress
      toward understanding the molecular mechanism of natural transformation in H.
      pylori, little is known about how competence is regulated or its relationship to
      DNA release. By measuring transformation incrementally throughout the growth
      curve, we show that H. pylori exhibits a novel pattern of competence with
      distinct peaks of transformation during both logarithmic and stationary growth
      phases. Furthermore, different H. pylori strains vary in the presence and timing
      of their competence peaks. We also examined the process of DNA release in
      relation to competence. Although extensive DNA release does not occur until late
      stationary phase, sufficient genomic DNA was present during the logarithmic phase
      to yield measurable transformants. These results demonstrate that the state of
      competence in H. pylori occurs in an unprecedented pattern during the growth
      curve with no clear relationship to DNA release.

PMID- 16436075
TI  - Functional analysis of L-serine O-acetyltransferase from Corynebacterium
      glutamicum.
AB  - We report here the function of L-serine O-acetyltransferase (SAT) from the
      glutamic acid-producing bacterium Corynebacterium glutamicum. Based on the genome
      sequence of C. glutamicum and the NH(2)-terminal amino-acid sequence, the gene
      encoding SAT (cysE) was cloned and expressed in C. glutamicum. Deletion analysis
      of the 5'-noncoding region showed a putative -10 region ((-27)TTAAGT(-22) or (
      26)TAAGTC(-21)) and a possible ribosome-binding site ((-12)AGA(-10)) just
      upstream from the start codon. We found that the SAT activity was sensitive to
      feedback inhibition by L-cysteine, and that SAT synthesis was repressed by L
      methionine. Further, cysE-disrupted cells showed L-cysteine auxotrophy,
      indicating that C. glutamicum synthesizes L-cysteine from L-serine via O-acetyl-L
      serine through the pathway involving SAT and O-acetyl-L-serine sulfhydrylase in
      the same manner as Escherichia coli.

PMID- 16436076
TI  - Structural determination of the Nod factors produced by Rhizobium gallicum bv.
      gallicum R602.
AB  - Rhizobium gallicum is a fast-growing bacterium found in European, Australian and
      African soils; it was first isolated in France. It is a microsymbiont which is
      able to nodulate plants of the genus Phaseolus. Rhizobium gallicum bv. gallicum
      R602 produces four extracellular signal molecules consisting of a linear backbone
      of N-acetyl glucosamine, bearing on the nonreducing terminal residue an N-methyl
      group and different N-acyl substituents. The four acyloligosaccharides terminate
      with a sulfated N-acetylglucosaminitol. This unit may be also acetylated. These
      structures were determined using carbohydrate and methylation analysis, mass
      spectrometric analysis and one-dimensional- and two-dimensional-nuclear magnetic
      resonance experiments. This work establishes the common structure that a
      lipochito-oligosaccharide must have so that the Rhizobium that produces and
      excretes it is able to nodulate plants of Phaseolus vulgaris. The substituents
      common to all the molecules are an N-methyl group and a C(18:1) fatty acid on the
      nonreducing terminal residue.

PMID- 16436077
TI  - Editorial.

PMID- 16436078
TI  - Representations of the dental surgery profession and the motivations given by
      second-year French students for applying for dental surgery.
AB  - AIM: The aim of the present study was to evaluate the representations odontology
      students had of their career path. Second-year odontology students were
      questioned about their own motivations and the motivations they attributed to
      dentists in choosing this profession. METHODS: The students were asked to
      complete a questionnaire during the first course and again after 5 months. It was
      thus possible to study the evolution of their motivations after 5 months of
      interactions with their fellow students and professors. RESULTS: Whether or not
      students were able to choose their career path following the selection
      examination at the end of the first year of the medical programme was an
      important variable in determining individual motivations and the motivations they
      attributed to dentists in choosing the dental profession. For example, students
      who were unable to choose their career path reported that they would like to work
      in the public health system, while those who were able to choose said they chose
      odontology as a vocation. The closing of the gap between the two groups during
      the period between the two questionnaires highlighted the increasing cohesion of
      the group. CONCLUSION: Beyond the differences between the motivations provided,
      this study showed that students who had not planned to become dentists before the
      selection examination needed some time to familiarise themselves with the
      situation and accept the change in their career path.

PMID- 16436079
TI  - Undergraduate and postgraduate dental students' 'reflection on learning': a
      qualitative study.
AB  - The aim of this study was to explore undergraduate and postgraduate dental
      students' understanding of a good learning experience by using 'reflection on
      learning' as described by Schon. Four groups of Year 4 BDS students and one group
      of postgraduate students in dental public health took part in a series of focus
      group discussions. The responses were grouped into four broad themes (a) active,
      practical and positive learning; (b) interactive/together learning; (c) personal
      learning; (d) theory into practice. Six educational models of good learning
      proposed by the students are described.

PMID- 16436080
TI  - Perceived sources of stress in Nigerian dental students.
AB  - The objective of this study was to identify sources of stress among dental
      students at the University of Lagos, Lagos, Nigeria. A modified Dental
      Environment Stress (DES) questionnaire was used to study the 137 students in
      years 3-6, of which 105 (76.6%) responded. Results show that the year 5 students
      indicated the highest level of stress overall on items relating to pre-clinical
      training with 21 (70%) recording aggregate DES score over the cut-off point for
      high stress. For clinical items, nearly all the students - 27(90%) of year 5 and
      24 (100%) of year 6 recorded aggregates over the cut-off point. The most
      important stressors were those related to the lack of provision of a well
      supported system of dental education in Nigeria in terms of availability of
      materials for clinical training and study materials. There were no significant
      differences in stress perception between genders. However, students who chose
      Medicine as their first choice for admission with Dentistry as an alternative
      experienced significantly higher overall mean and higher mean scores for most
      items. In conclusion, it appears there is a need to improve support for dental
      education in Nigeria.

PMID- 16436082
TI  - Noise levels in dental schools.
AB  - OBJECTIVE: To measure and analyse noise levels in the learning-teaching
      activities at the Dental School of the University of Porto (Portugal). MATERIALS
      AND METHODS: Sound levels were measured in five different practice areas and
      laboratories, selected as representative of a variety of learning-teaching
      activities. The noise levels were determined using a precision sound level meter
      that was positioned at ear level and at 1 m distance from the operator. RESULTS:
      The noise levels registered vary between 60 and 99 dB(A) and are similar to the
      data of other international studies. The results recorded differences in sound
      levels when the equipment was merely turned on and during cutting operations.
      Differences between brand new and used equipment were also noted. It appears that
      hearing damage risk may be lesser amongst dentists who use brand new equipment.
      CONCLUSION: The noise levels detected in this study are considered to be close to
      the limit of risk of hearing loss.

PMID- 16436081
TI  - Effect of tutorial input in addition to augmented feedback on manual dexterity
      training and its retention.
AB  - Virtual reality (VR) simulators can be used as tools in manual dexterity
      training. The visual feedback guides the subject towards proper performance but
      creates, at the same time, some dependency on this feedback. To overcome this
      drawback, the effect of adjunct tutorial input on motor learning behaviour was
      examined. Novice dental students were randomly assigned to one of two training
      groups or to a non-training control group, given the task of preparing a
      geometrical class 1 cavity in phantom teeth. The feedback (FB) group trained
      under augmented visual feedback conditions, provided by the VR system (DentSim).
      The feedback-plus (FB+) group received, in addition, standardised expert input to
      enrich the augmented feedback information. The control group, consisting of same
      year students, did not participate in any training programme. All preparations
      were evaluated by the VR scoring system. Performance analyses revealed an overall
      trend towards significant improvement with practice for the training groups.
      Performance of the FB+ group was most accurate across training. After 1 day and 3
      weeks of no practice, both training groups outperformed the control group. After
      4 months, however, only the FB+ condition was significantly more accurate than
      the control group. The same tendency was noted for the transfer tests.
      Consequently, cavity preparation experience on a VR system under the condition of
      frequently provided feedback supplemented with expert input was most beneficial
      to long time learning.

PMID- 16436083
TI  - Teaching of posterior composite resin restorations in undergraduate dental
      schools in Ireland and the United Kingdom.
AB  - PURPOSE: The aim of this study was to investigate the current teaching of
      posterior composite resin restorations to undergraduate dental students in
      Ireland and the United Kingdom (UK). The investigation was a follow-up to a
      survey undertaken in 1997. MATERIALS AND METHODS: A questionnaire was distributed
      by e-mail to the Heads of Departments of Restorative Dentistry/Units of Operative
      Dentistry in each of the 15 dental schools with undergraduate dental degree
      programmes in Ireland and the UK. The questionnaire sought information relating
      to the teaching of posterior composite resin restorations in each dental school.
      RESULTS: Fifteen completed questionnaires were returned (response rate = 100%).
      All schools (n = 15) taught the placement of composite resin restorations in
      occlusal cavities, 14 schools taught composite resin placement in two-surface
      occlusoproximal cavities and nine schools taught composite resin placement in
      three-surface occlusoproximal cavities. Respondents anticipated that the amount
      of preclinical teaching of posterior composite resin placement will increase
      twofold over the next 5 years, whilst the corresponding teaching of amalgam will
      fall to two-thirds its current level. Variation was found between dental schools
      in the teaching of the principles of cavity design, contraindications to
      placement, indications for lining and basing techniques, matrix and wedging
      techniques, and the use of curing lights. CONCLUSIONS: The amount of teaching of
      posterior composite resin restorations in undergraduate dental schools in Ireland
      and the UK has increased since the time of a previous survey in 1997. Composite
      resin may soon equal or overtake amalgam as the material of choice when restoring
      posterior cavities in Irish and UK dental schools. There was, however, much
      variation in the nature and extent of the teaching and the techniques taught.

PMID- 16436084
TI  - Perspectives of staff on student outreach placements.
AB  - OBJECTIVE: To explore the perspectives of placement staff on outreach training.
      INTERVENTION: Block clinical placements in primary care settings for dental
      undergraduates and hygiene and therapy students. METHOD: After completion of the
      placements, 32 participating staff across nine primary care locations took part
      in qualitative interviews and focus groups. The staff provided data on placement
      organisation, the students' development and their supervision, and any effects on
      themselves as hosts. RESULTS: The major themes included the learning environment,
      supervision and communication. The staff saw benefits to students in working in a
      smaller primary care clinic with nursing support and immediately available
      supervision by a dental generalist. Other benefits included increased confidence,
      broader clinical experience and applying theoretical learning to new communities.
      Effective communication and adequate resourcing were critical success factors.
      There was some disruption of clinics' normal working, but many unanticipated
      benefits. Staff supported the outreach placements in primary care settings to
      enhance students' dental education. CONCLUSIONS: These findings provide a
      planning and evaluation framework for dental educators involved in outreach.

PMID- 16436085
TI  - Hand and nickel-titanium root canal instrumentation performed by dental students:
      a micro-computed tomographic study.
AB  - The aim of this study was to evaluate root canals instrumented by dental students
      using the modified double-flared technique, nickel-titanium (NiTi) rotary System
      GT files and NiTi rotary ProTaper files by micro-computed tomography (MCT). A
      total of 36 root canals from 18 mesial roots of mandibular molar teeth were
      prepared; 12 canals were prepared with the modified double-flared technique,
      using K-flexofiles and Gates-Glidden burs; 12 canals were prepared using System
      GT and 12 using ProTaper rotary files. Each root was scanned using MCT
      preoperatively and postoperatively. At the coronal and mid-root sections, System
      GT and ProTaper files produced significantly less enlarged canal cross-sectional
      area, volume and perimeter than the modified double-flared technique (P < 0.05).
      In the mid-root sections there was significantly less thinning of the root
      structure towards the furcation with System GT and ProTaper (P < 0.05). The
      rotary techniques were both three times faster than the modified double-flared
      technique (P < 0.05). Qualitative evaluation of the preparations showed that both
      ProTaper and System GT were able to prepare root canals with little or no
      procedural error compared with the modified double-flared technique. Under the
      conditions of this study, inexperienced dental students were able to prepare
      curved root canals with rotary files with greater preservation of tooth
      structure, low risk of procedural errors and much quicker than with hand
      instruments.

PMID- 16436086
TI  - Does lipoprotein(a) predict risk in type 2 diabetes?

PMID- 16436087
TI  - Heart specific up-regulation of genes for B-type and C-type natriuretic peptide
      receptors in diabetic mice.
AB  - BACKGROUND: Diabetes may cause cardiomyopathy characterized by cardiac fibrosis.
      Recent studies of genetically modified mice have elucidated a role of the
      natriuretic peptides (NP), type-A and type-B (ANP and BNP), and their common
      receptor [natriuretic peptide receptor (NPR), type-A] in development of cardiac
      fibrosis. The role of NP type-C (CNP) and NPR type-B (NPR-B) in the heart is less
      well established. In this study we examined if diabetes alters heart expression
      of the genes encoding the NP and its receptors. MATERIALS AND METHODS: Cardiac
      mRNA was quantified by real-time PCR in diabetic streptozotocin (STZ)-treated and
      ob/ob-mice and nondiabetic control mice. RESULTS: The ob/ob-mice with type-II
      diabetes displayed highly significant increases of the cardiac mRNA expression of
      NPR-B and NPR-C while the expression levels of NPR-A, ANP, BNP, and CNP mRNA were
      similar in ob/ob-mice and controls. Mice with STZ-induced type-I diabetes also
      showed an increase of heart NPR-B mRNA expression at 12 weeks, but not at 3, 6 or
      9 weeks after STZ-treatment. The ANP and NPR-C mRNA expressions were only altered
      after 3 weeks, whereas BNP, CNP and NPR-A mRNA expressions were not altered in
      STZ-treated-mouse hearts at any of the time points. CONCLUSIONS: The results show
      that diabetes in mice confers increased NPR-B gene expression in the heart,
      suggesting that increased NPR-B signalling may affect development of diabetic
      cardiomyopathy.

PMID- 16436088
TI  - Effects of simvastatin withdrawal on serum matrix metalloproteinases in
      hypercholesterolaemic patients.
AB  - BACKGROUND: Serum matrix metalloproteinase (MMP) levels have been related to
      clinical outcomes in patients with coronary artery disease. Though statin
      treatment might reduce serum MMPs the change of levels after statin withdrawal
      remains obscure. MATERIALS AND METHOD: Sixty-one consecutive
      hypercholesterolaemic patients whose lipid profiles had been well controlled by
      regular simvastatin (20 mg day(-1)) treatment for more than 6 months were
      enrolled. Statin was discontinued after their lipid profiles reached the
      treatment goal of the ATP-III guideline. The lipid profiles, serum MMP-2, MMP-3
      and MMP-9, tissue inhibitor of MMP and highly sensitive C-reactive protein
      (hsCRP) levels were measured on the day of simvastatin withdrawal and 120 days
      later. A further 50 hyperlipidaemia patients who had never received statin
      treatment (positive control group) and 28 healthy patients with normal lipid
      profiles (negative control group) were also studied as control groups. RESULTS:
      While the lipid profiles had been normalized, the levels of serum inflammatory
      markers were still higher in hypercholesterolaemic patients than in the healthy
      subjects. Up to 120 days after statin withdrawal there was no coronary event, but
      the lipid profiles and serum hsCRP levels had significantly rebounded in study
      patients. However, serum MMP-2 and MMP-9 levels remained unchanged and the MMP-3
      level was even further reduced after statin withdrawal (115.04 +/- 84.54 vs.
      92.71 +/- 66.71 ng mL(-1), P = 0.022). Moreover, the amplitudes of variation (%)
      of each parameter including MMPs, TIMP, hsCRP and lipid profiles after statin
      withdrawal were inversely correlated to their respective baseline levels before
      withdrawal (r = -0.702 to -0.284; P < 0.005). CONCLUSIONS: The effects of short
      term discontinuation of statin were different on serum hsCRP and MMPs levels in
      hypercholesterolaemic patients. While lipid profiles and serum hsCRP level had
      rebounded the serum MMPs levels were still unchanged, or even reduced, suggesting
      the prolonged effect of statin treatment, especially on serum MMP-3 level up to
      120 days after simvastatin withdrawal. Further work is required to clarify the
      situation both in terms of these serum markers and clinical effects.

PMID- 16436089
TI  - Effects of antibodies obtained from patients with dilated cardiomyopathy on the
      function of isolated rat hearts.
AB  - BACKGROUND: Cardiac autoantibodies may play a pathophysiological role in cardiac
      dysfunction of patients suffering from dilated cardiomyopathy (DCM).
      Immunoadsorption (IA), which removes antibodies from patients' plasma, may
      consequently improve cardiac function in DCM. The functional effects of DCM
      antibodies are only partly understood. MATERIALS AND METHODS: DCM patients (n =
      10) were treated with IA by application of antibody columns directed against
      human immunoglobulin (Ig). IA was also performed with plasma taken from 10
      healthy donors (controls). The antibodies eliminated and purified by IA were
      collected and dialysed. Rat hearts were isolated and perfused retrogradely via
      the aorta in Langendorff mode. During constant-pressure and constant-volume
      perfusion of the hearts, the influence of diluted antibodies on contractility,
      relaxation, and on coronary perfusion was analysed. RESULTS: Antibodies obtained
      from controls had no effect on contractility and relaxation of isolated perfused
      hearts during constant-pressure and constant-volume perfusion. In contrast,
      during constant-pressure perfusion, collected DCM antibodies caused immediate and
      dose-related reduction of contractility (dLVP/dtmax: dilution -1:32 = -7.1 +/-
      1.1%; dilution -1:2 = -20.1 +/- 2.1%; P < 0.001) and diastolic relaxation
      (dLVP/dtmin: dilution -1:32 = -11.1 +/- 1.5%; dilution -1:2 = -23.9 +/- 2.2%; P <
      0.001). The heart rate did not change significantly in either group. The effects
      of DCM antibodies on contractility and relaxation remained detectable during
      constant-volume perfusion. The observed reduction of contractility and diastolic
      relaxation was accompanied by impairment of coronary perfusion. CONCLUSION: In
      the rat heart, antibodies obtained from DCM patients may impair contractility and
      relaxation, and thereby probably also coronary perfusion.

PMID- 16436090
TI  - Lipoprotein(a), type 2 diabetes and vascular risk in coronary patients.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] is an important cardiovascular risk factor in
      the general population. However, prospective data on the vascular risk conferred
      by Lp(a) in patients with diabetes mellitus are scarce and controversial. It is
      not known whether the diabetic state affects the association of Lp(a) with
      vascular events among coronary patients. DESIGN: We measured Lp(a) in 587
      consecutive patients undergoing coronary angiography for the evaluation of
      coronary artery disease. The incidence of vascular events was recorded over 4
      years. RESULTS: At baseline, Lp(a) was significantly lower in patients with type
      2 diabetes (T2DM) (n = 136) than in nondiabetic individuals (11 (0.8-30) mg dL(
      1) vs. 16 (0.8-51) mg dL(-1); P = 0.025). Prospectively, Lp(a) was a strong and
      independent predictor of vascular events in nondiabetic patients (standardized
      adjusted hazard ratio (HR) = 1.461 (1.121-1.904); P = 0.005), but not in patients
      with T2DM [HR = 0.812 (0.539-1.223); P = 0.320]. An interaction term diabetes x
      Lp(a) was significant (P = 0.008), indicating that Lp(a) was a significantly
      stronger predictor of vascular events in nondiabetic patients than in patients
      with T2DM. CONCLUSIONS: Lp(a) in diabetic coronary patients is low and not
      associated with the incidence of vascular events. Although measurement of Lp(a)
      provides useful information in nondiabetic coronary patients, it is of little
      value in coronary patients with T2DM.

PMID- 16436091
TI  - Lipoprotein profiles in plasma and interstitial fluid analyzed with an automated
      gel-filtration system.
AB  - BACKGROUND: High-quality methods for lipoprotein characterization are warranted
      in studies on various metabolic diseases. MATERIALS AND METHODS: An automated
      system for size-exclusion chromatography (SEC) of lipoproteins using commercially
      available components is described. Cholesterol or triglyceride content in
      separated lipoproteins from plasma and interstitial fluid (IF) was continuously
      determined on-line using microlitre sample volumes. RESULTS: The lipoprotein
      assay showed a good concordance with the classic ultra
      centrifugation/precipitation technique using fresh or frozen samples.
      Determination of lipoproteins in IF obtained from vacuum-induced skin blisters
      from 18 healthy subjects revealed that very low density lipoprotein (VLDL), low
      density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels
      were 18%, 19% and 25%, respectively, of concomitant plasma concentrations. The
      size-exclusion chromatography (SEC) system also allows for triglyceride
      determination on-line and it could be shown that the system is advantageous for
      an accurate determination of triglycerides in conditions when there are high
      levels of glycerol, e.g. in mice and in patients with hyperglycerolaemia (pseudo
      hypertriglyceridaemia). CONCLUSIONS: The described system should be of value in
      studies where detailed lipoprotein analysis is warranted and particularly when
      significant sample series with small volumes are available. Our data also suggest
      that there is a 4-5.5-fold concentration gradient between plasma and IF for the
      three major plasma lipoproteins.

PMID- 16436092
TI  - Indomethacin disrupts the protective effect of phosphatidylcholine against bile
      salt-induced ileal mucosa injury.
AB  - BACKGROUND: Indomethacin (Indo) exerts local toxic effects on small intestinal
      mucosa, possibly in association with hydrophobic bile salts. We investigated the
      potential toxic effects of Indo on ileal mucosa and the role of
      phosphatidylcholine (PC). MATERIALS AND METHODS: Transmucosal resistance and Na
      fluorescein permeability of ileal mucosa segments from female Wistar rats were
      determined in Ussing chambers during a 30-min incubation with model systems
      containing: control-buffer, taurodeoxycholate (TDC), Indo, TDC-Indo, TDC-PC, or
      TDC-PC-Indo. Decrease of resistance and increase of permeability were considered
      as parameters for mucosal injury. After incubation in Ussing chambers, the
      histopathology was examined to quantify the extent of mucosal injury. Also, in
      CaCo-2 cells, LDH-release was determined as a measure of cytotoxicity, after
      incubation with various model systems. RESULTS: Decrease of resistance and
      increase of permeability were highest in systems containing TDC-Indo (P < 0.01).
      Phosphatidylcholine protected against the cytotoxic effects of TDC in absence of
      Indo only. Extent of mucosal injury by histological examination was also highest
      in systems containing TDC-Indo (P = 0.006). Again, PC exhibited protective
      effects in absence of Indo only. The LDH-release by CaCo2-cells was strongest in
      TDC-Indo systems (P < 0.001). CONCLUSIONS: Indomethacin disrupts protective
      effects of PC against bile salt-induced ileal mucosa injury. This finding is
      relevant for small intestinal injury induced by non-steroidal anti-inflammatory
      drugs.

PMID- 16436093
TI  - Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits ethanol-induced
      activation of pancreatic stellate cells.
AB  - BACKGROUND: Activated pancreatic stellate cells (PSCs) play a central role in the
      pathogenesis of pancreatic fibrogenesis and inflammation. Ethanol, a major cause
      of chronic pancreatitis, directly induces PSC activation and oxidative stress.
      Inhibition of PSC activation or stimulation to PSC might be an effective
      therapeutic strategy for the prevention of pancreatic fibrosis, and (-)
      epigallocatechin-3-gallate (EGCG), a major component of green tea extracts, is a
      potent antioxidant of polyphenols. Therefore, we examined the mechanisms through
      which ethanol induces oxidative stress on PSCs and evaluated the effect of EGCG
      on activation and cell functions of ethanol-stimulated PSCs. MATERIALS AND
      METHODS: The PSCs were isolated from the pancreas of male Wister rats with
      Nycodenz gradient methods and cells between passages one and four were used.
      Isolated PSCs were cultured with ethanol (50 mM) in the absence or presence of
      EGCG (5 microM or 25 microM). RESULTS: The EGCG pre-treatment abolished ethanol
      induced lipid peroxidation of the cell membrane, loss of total superoxide
      dismutase (SOD) activity and suppressed ethanol-induced gene expressions of Mn-
      and Cu/Zn-SOD. EGCG also suppressed ethanol-induced p38 mitogen-activated protein
      (MAP) kinase phosphorylation, alpha-smooth muscle actin production in PSCs and
      activated transforming growth factor-beta1 secretion into the medium.
      Furthermore, EGCG inhibited ethanol-induced type-I procollagen production and
      collagen secretion. In addition, EGCG inhibited transformation of freshly
      isolated cells to activated myofibroblast-like phenotype. CONCLUSIONS: Our
      results suggest that green tea and polyphenols could prevent pancreatic fibrosis
      by inhibiting PSC activation through the antioxidative effect.

PMID- 16436094
TI  - Influence of a subsequent meal on the oro-cecal transit time of a solid test
      meal.
AB  - BACKGROUND: Oro-cecal transit time (OCTT) is determined for clinical diagnostics
      of intestinal complaints and research purposes. Ingestion of a subsequent meal
      during the test period shortens the OCTT of a liquid test meal (glucose
      solution), as previously reported. This study was conducted to determine whether
      the same phenomenon occurs after ingestion of a solid test meal. MATERIALS AND
      METHODS: The OCTT of a pancake was measured with the lactose-[(13)C]-ureide
      breath test on two occasions in 28 volunteers. All the volunteers took the same
      subsequent meal once at 4 h and at 6 h after ingestion of the pancake. RESULTS:
      In 16 of the 56 tests no increase in breath-(13)CO(2) was observed. No
      statistically significant difference was found between the OCTTs of the test meal
      after ingestion of the subsequent meal at 4 h or 6 h (367; 311-405 min and 290;
      370-405 min, median quartiles, respectively) (P = 0.14, n = 18). Only a subgroup
      (n = 4) with a short OCTT in the test with the 4-h subsequent meal (278; 259-296
      min) tended to have a longer OCTT in the test with the 6-h subsequent meal (390;
      379-401 min; P = 0.059). CONCLUSION: The effect of the ingestion of a subsequent
      meal on the transit time of a test meal is shown to be dependent on the physical
      form and/or caloric content of the test meal.

PMID- 16436095
TI  - Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Angiogenesis has been suggested to play an important role in
      inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum
      markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor
      Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD).
      MATERIALS AND METHODS: Serum Ang-2 and Tie-2 serum levels were measured in 160
      IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using
      commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2
      levels were correlated with the disease activity, as well as the type,
      localization and treatment of the disease. RESULTS: Median serum Ang-2 and Tie-2
      levels were significantly higher in both the UC patients and the CD patients
      compared with the healthy controls (P < 0.05 and P < 0.001, respectively). The
      IBD patients with early disease (diagnosis < 2 years) had significantly higher (P
      = 0.04) median serum Ang-2 levels but significantly lower (P = 0.02) median serum
      Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2
      years). The CD patients with active disease had significantly higher levels of
      Ang-2 compared with non-active disease (P = 0.02). Serum levels of both Ang-2 and
      Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood
      cell count, platelet count and albumin. CONCLUSIONS: Serum Ang-2 and Tie-2 levels
      are elevated in patients with IBD. These markers may mediate angiogenesis and
      vascular permeability in the mucosa of patients with IBD.

PMID- 16436096
TI  - Hypoxic inhibition of human myometrial contractions in vitro: implications for
      the regulation of parturition.
AB  - BACKGROUND: Insufficient tissue oxygenation is a likely contribution to weak,
      inco-ordinate human uterine contractile activity characteristic of prolonged,
      dysfunctional labour. However, the direct effects of hypoxia on human myometrial
      contractility has, surprisingly, not yet been detailed. Therefore, we report the
      influence of hypoxia on spontaneous and agonist-induced carbachol, prostaglandin
      (PGF2alpha), and oxytocin contractions of myometria from nonpregnant and pregnant
      women. MATERIALS AND METHODS: Uterine biopsies were obtained from pregnant women
      at term undergoing elective Caesarean section and nonpregnant women undergoing
      hysterectomy. Myometrial strips were equilibrated at 37 degrees C in normoxic
      physiological salt solution (95% air/5% CO(2)) and the influence of hypoxia (95%
      N(2)/5% CO(2)) on contractility was investigated. RESULTS: Hypoxia resulted in a
      significant reduction in spontaneous contractile function; nonpregnant tissue was
      less resistant to the deleterious effects of hypoxia. Agonist-induced
      contractions, while being more resistant to hypoxia than spontaneous
      contractions, were also significantly inhibited. In myometria of pregnant women
      the PGF2alpha- or oxytocin-induced contractility was more resistant to hypoxia
      than carbachol. Finally, the inhibitory actions of hypoxia were exacerbated with
      repeated oxytocin administration with a more severe effect on contractile
      integral than on initial phasic contraction amplitude. CONCLUSIONS: We detail,
      for the first time, the effects of hypoxia on contractility of human myometria
      from nonpregnant and pregnant women. Physiologically important uterotonic agents
      are more resistant to the effects of hypoxia than spontaneous contractions
      although repeated stimulation with oxytocin during hypoxia results in
      progressively less force. The results indicate that if significant hypoxia occurs
      in vivo then it is a likely contributory factor to the pathways underlying
      prolonged dysfunctional labour.

PMID- 16436097
TI  - Prevalence of obesity in Sweden.
AB  - Although the prevalence of obesity in Sweden still is low in an international
      perspective, the development during the last decades is alarming in adults,
      adolescents and children alike. The prevalence of obesity [body mass index (BMI)
      > 30 kg m-2] in adults has doubled during the last two decades and is now
      approximately 10% in both men and women, according to estimates based on self
      reported BMI from repeated random samples of the population. However, prevalence
      estimates based on measured BMI from the WHO MONICA study indicate that the self
      reported data result in underestimates. In military conscripts, the prevalence of
      obesity (BMI > 30 kg m-2) almost quadrupled to 3.2% from 1971 to 1995, while the
      overweight fraction (BMI > 25 kg m-2) more than doubled to 16.3%. The development
      in younger age groups seems to be similar; the prevalence of overweight
      [International Obesity Task Force (IOTF)/Cole] in children aged 10 years in
      Gothenburg has doubled to 18% (2.9% obese) during the last decade, and similar
      figures have been reported in other studies. However, most reports on childhood
      overweight stem from the larger metropolitan areas, and hence may be
      underestimates because of the urban-rural influence on obesity-status. Recent
      data from non-urban areas in the northern part of Sweden estimate the prevalence
      of overweight (BMI > 20 kg m-2) in 10-year-olds to above 30%. In the most
      comprehensive study in children, including both rural and urban areas, BMI was
      measured among all children aged 10 years (n = 5517; 92.7% of the population) in
      the county of Ostergotland, and the prevalence of overweight (IOTF/Cole) was 22%
      in both boys and girls, of which 4% and 5% were obese respectively.

PMID- 16436098
TI  - Poverty and the extent of child obesity in Canada, Norway and the United States.
AB  - The goal of this paper is to compare the extent of child obesity in Canada,
      Norway and the United States. As child poverty is an important correlate of child
      obesity, we wish to examine the potential role of international differences in
      child poverty in explaining international differences in the extent of child
      obesity. We use three representative microdata surveys containing parental
      reports of child height and weight collected in the mid-1990s in Canada, Norway
      and the US. We calculate both the prevalence and proportional severity of child
      obesity for 6-11-year-old children in each country, and represent the 'extent' of
      obesity diagrammatically. Differences in patterns of child poverty are similarly
      depicted. Obesity extent is also compared for poor and non-poor children in
      Canada and the US. Finally, child obesity in the three countries is compared
      using only non-poor children where we find that the extent of child obesity is
      much lower in Norway than in Canada or the US. The pattern apparent for obesity
      is remarkably similar to that found for child poverty. In Canada and especially
      in the US, we find a much greater extent of obesity for poor than non-poor
      children. However, when we compare only non-poor children in the three countries,
      although the magnitude of difference is smaller, it remains clear that Norwegian
      children are much less likely to be obese. Policy and research directed towards
      reducing the extent of child obesity in both Canada and the US should pay
      particular attention to issues of child poverty.

PMID- 16436099
TI  - The biomechanics of restricted movement in adult obesity.
AB  - In spite of significant advances in the knowledge and understanding of the multi
      factorial nature of obesity, many questions regarding the specific consequences
      of the disease remain unanswered. In particular, there is a relative dearth of
      information pertaining to the functional limitations imposed by overweight and
      obesity. The limited number of studies to date have mainly focused on the effect
      of obesity on the temporospatial characteristics of walking, plantar foot
      pressures, muscular strength and, to a lesser extent, postural balance.
      Collectively, these studies have implied that the functional limitations imposed
      by the additional loading of the locomotor system in obesity result in aberrant
      mechanics and the potential for musculoskeletal injury. Despite the greater
      prevalence of musculoskeletal disorders in the obese, there has been surprisingly
      little empirical investigation pertaining to the biomechanics of activities of
      daily living or into the mechanical and neuromuscular factors that may predispose
      the obese to injury. A better appreciation of the implications of increased
      levels of body adiposity on the movement capabilities of the obese would afford a
      greater opportunity to provide meaningful support in preventing, treating and
      managing the condition and its sequelae. Moreover, there is an urgent need to
      establish the physical consequences of continued repetitive loading of major
      structures of the body, particularly of the lower limbs in the obese, during the
      diverse range of activities of daily living.

PMID- 16436100
TI  - 'Take the stairs instead of the escalator': effect of environmental prompts on
      community stair use and implications for a national 'Small Steps' campaign.
AB  - The US government initiated a national health campaign targeting 100 'small step'
      lifestyle changes to combat obesity. Small Step #67 advocates stair instead of
      escalator usage in public settings. The aim of this study is to evaluate the
      effects of motivational signs prompting stair use over escalator use on
      pedestrians' stair usage in commuter settings. Eight studies, testing the effects
      of motivational prompts on stair vs. escalator usage in public settings, were
      reviewed. Participant and study attributes were descriptively coded. Effect size
      was calculated as the change in percent units of stair users during the
      intervention phases vs. the baseline phase. The average study included
      approximately 45,000 observations that were recorded across an average of 15
      weeks of intervention. The mean +/- SD change in percent units of stair users was
      2.8% +/- 2.4% (P < 0.001), and effects were twice as large in females (4.8%) as
      in males (2.4%). The number of stairs/building, baseline stair use, and total
      intervention weeks predicted change in stair use, although the effects were
      clinically miniscule. In a hypothetical city intervention, we projected that a
      2.8% increase in stair usage would result in a weight loss and/or weight gain
      prevention of 300 g/person/year among new stair users. In sum, point-of-decision
      motivational signs may help communities attain Small Step #67. However, the
      singular impact of this community intervention on correcting energy imbalance may
      be minimal, having slight impact itself on reducing the national obesity
      prevalence.

PMID- 16436101
TI  - Energy balance adiposity and breast cancer - energy restriction strategies for
      breast cancer prevention.
AB  - Excess adiposity over the pre- and postmenopausal years is linked to risk of
      postmenopausal breast cancer. Weight loss could potentially reduce risk amongst
      those with excess weight via beneficial effects on the hormonal (decreased
      circulating levels of oestradiol, testosterone, insulin) and secretory profiles
      of adipocytes (decreased production of leptin, tumour necrosis factor-alpha,
      interleukin 6 and increased production of adiponectin). Only modest reductions in
      adipose tissue are achieved and sustained with current weight loss programmes,
      which makes strategies to mitigate the adverse metabolic effect of adiposity a
      priority for cancer prevention. The adverse hormonal and secretory effects of
      adipose tissue are influenced substantially by acute changes in energy balance
      prior to changes in adiposity. Human and animal studies have shown dietary energy
      restriction to bring about favourable changes in circulating levels of insulin,
      leptin, sex hormone binding globulin, insulin-like growth factor-1, oestradiol,
      testosterone, reactive oxygen species, and the production and secretion of
      locally acting adipokines and inflammatory cytokines, that is, increased
      adiponectin and decreased interleukin-6. Achieving and sustaining energy
      restriction remains a difficult challenge. Intermittent energy restriction is a
      potential strategy for promoting periods of energy restriction on a long-term
      basis. Animal and human data suggest that intermittent energy restriction may
      have cancer preventative effects beyond that of chronic energy restriction and
      weight loss. Intermittent energy restriction may be a potential strategy for the
      primary prevention of breast cancer.

PMID- 16436102
TI  - Low-carbohydrate diets: nutritional and physiological aspects.
AB  - Recently, diets low in carbohydrate content have become a matter of international
      attention because of the WHO recommendations to reduce the overall consumption of
      sugars and rapidly digestible starches. One of the common metabolic changes
      assumed to take place when a person follows a low-carbohydrate diet is ketosis.
      Low-carbohydrate intakes result in a reduction of the circulating insulin level,
      which promotes high level of circulating fatty acids, used for oxidation and
      production of ketone bodies. It is assumed that when carbohydrate availability is
      reduced in short term to a significant amount, the body will be stimulated to
      maximize fat oxidation for energy needs. The currently available scientific
      literature shows that low-carbohydrate diets acutely induce a number of
      favourable effects, such as a rapid weight loss, decrease of fasting glucose and
      insulin levels, reduction of circulating triglyceride levels and improvement of
      blood pressure. On the other hand some less desirable immediate effects such as
      enhanced lean body mass loss, increased urinary calcium loss, increased plasma
      homocysteine levels, increased low-density lipoprotein-cholesterol have been
      reported. The long-term effect of the combination of these changes is at present
      not known. The role of prolonged elevated fat consumption along with low
      carbohydrate diets should be addressed. However, these undesirable effects may be
      counteracted with consumption of a low-carbohydrate, high-protein, low-fat diet,
      because this type of diet has been shown to induce favourable effects on feelings
      of satiety and hunger, help preserve lean body mass, effectively reduce fat mass
      and beneficially impact on insulin sensitivity and on blood lipid status while
      supplying sufficient calcium for bone mass maintenance. The latter findings
      support the need to do more research on this type of hypocaloric low-carbohydrate
      diet.

PMID- 16436103
TI  - Metabolically active functional food ingredients for weight control.
AB  - The scale of the obesity epidemic creates a pressing consumer need as well as an
      enormous business opportunity for successful development and marketing of food
      products with added benefits for weight control. A number of proposed functional
      food ingredients have been shown to act post-absorptively to influence substrate
      utilization or thermogenesis. Characteristics and supporting data on conjugated
      linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine,
      caffeine, capsaicin and calcium, are reviewed here, giving examples of how these
      could act to alter energy expenditure or appetite control. Consideration is also
      given to other factors, in addition to efficacy, which must be satisfied to get
      such ingredients into foods. We conclude that, for each of the safe, putatively
      metabolically active agents, there remain gaps in clinical evidence or knowledge
      of mechanisms, which need to be addressed in order to specify the dietary
      conditions and food product compositions where these ingredients could be of most
      benefit for weight control.

PMID- 16436104
TI  - Citrus aurantium and synephrine alkaloids in the treatment of overweight and
      obesity: an update.
AB  - Obesity is a major health problem facing the developed and developing world.
      Efforts by individuals, health professionals, educators, and policy makers to
      combat the escalating trend of growing obesity prevalence have been multifaceted
      and mixed in outcome. Various dietary supplements have been marketed to reduce
      obesity. These products have been suggested to accomplish this by decreasing
      energy intake and energy absorption, and/or increasing metabolic rate. Ephedra,
      one such supplement, was banned from sale in the US market because of concerns
      about adverse events. Another substance, Citrus aurantium, which contains several
      compounds including synephrine alkaloids, has been suggested as a safe
      alternative. This review examines the evidence for safety and efficacy of C.
      aurantium and synephrine alkaloids as examined in animal studies, clinical weight
      loss trials, acute physiologic studies and case reports. Although at least three
      reviews of C. aurantium have been published, our review expands upon these by:
      (i) distinguishing and evaluating the efficacy of C. aurantium and related
      compounds; (ii) including results from previously unreviewed research; (iii)
      incorporating recent case reports that serve to highlight, in an anecdotal way,
      potential adverse events related to the use of C. aurantium and related
      compounds; and (iv) offering recommendations to guide the design of future trials
      to evaluate the safety and efficacy of C. aurantium. While some evidence is
      promising, we conclude that larger and more rigorous clinical trials are
      necessary to draw adequate conclusions regarding the safety and efficacy of C.
      aurantium and synephrine alkaloids for promoting weight loss.

PMID- 16436105
TI  - Obesity drugs and their targets: correlation of mouse knockout phenotypes with
      drug effects in vivo.
AB  - Sequencing of the human genome has yielded thousands of potential drug targets.
      The difficulty now is in determining which targets have real therapeutic value
      and should be the focus of a drug discovery effort. The available evidence
      suggests that knockout technology can be used prospectively to identify targets
      that are amenable to drug development for the treatment of a variety of diseases.
      This review compares the knockout phenotypes of 21 potential obesity targets with
      the effects of therapeutics designed for those targets on rodents and, when data
      were available, on humans. The phenotypes of obesity target knockouts model the
      effects seen when therapeutics designed for those obesity targets are delivered
      to rodents; of the 21 obesity targets reviewed, 16 showed a correspondence
      between knockout phenotype and drug effect in mice and/or rats. This suggests
      that, at least in terms of evaluating obesity targets, it is rare for
      compensatory developmental changes caused by the gene knockout to prevent
      detection of the relevant phenotype. In the majority of cases, the knockout
      phenotypes also modelled the effects seen when the relevant therapeutics were
      delivered to humans. Thus, it seems rational to use mouse knockout technology
      prospectively to identify genes that regulate body fat in vivo, and then to
      develop anti-obesity therapeutics by targeting the human protein products of
      these genes. Ultimately, the value of using this approach to identify novel
      targets for human anti-obesity therapies will be judged by future studies
      examining the anti-obesity effect, in humans, of the therapeutics that result
      from this approach.

PMID- 16436106
TI  - Similia similibus curentur = like cures like.

PMID- 16436107
TI  - The prevention of overweight and obesity in children and adolescents: a review of
      interventions and programmes.
AB  - Overweight and obesity are serious, large-scale, global, public health concerns
      requiring population-based childhood overweight and obesity prevention. The
      overall objective of this review is to identify aspects of successful childhood
      overweight prevention programmes. This objective will be met by assessing
      existing interventions quantitatively as well as qualitatively, identifying
      efficacy, effectiveness and implementation, and evaluating potential adverse
      effects of previous studies. This review was limited to school-based studies with
      a quantitative evaluation using anthropometric outcomes and that intervene on
      diet or activity-related behaviours. Quantitative and qualitative approaches are
      used to identify factors related to successful interventions as well as adverse
      consequences. Sixty-eight per cent of the interventions, or 17 of the 25, were
      'effective' based on a statistically significant reduction in body mass index
      (BMI) or skin-folds for the intervention group. Four interventions were effective
      by BMI as well as skin-fold measures. Of these, two targeted reductions in
      television viewing. The remaining two studies targeted direct physical activity
      intervention through the physical education programme combined with nutrition
      education. Of the interventions reported here, one was effective in reducing
      childhood overweight but was also associated with an increase in underweight
      prevalence. Few other studies reported outcomes for underweight. The majority of
      overweight/obesity prevention programmes included in this review were effective.
      Physical education in schools and reducing television viewing are two examples of
      interventions that have been successful. Because few studies report on
      underweight prevalence, this review recommends giving more attention to
      preventing adverse outcomes by reporting the intervention impact on the frequency
      distribution for both BMI and adiposity measures.

PMID- 16436108
TI  - British Society for Matrix Biology Autumn 2005, 25th anniversary meeting.
      Abstracts.

PMID- 16436110
TI  - A preliminary in vitro study into the use of IL-1Ra gene therapy for the
      inhibition of intervertebral disc degeneration.
AB  - Conventional therapies for low back pain (LBP) are purely symptomatic and do not
      target the cause of LBP, which in approximately 40% of cases is caused by
      degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit
      the process of degeneration would be a potentially valuable treatment for LBP.
      There is increasing evidence for a role for IL-1 in DIVD. A natural inhibitor of
      IL-1 exists, IL-1Ra, which would be an ideal molecular target for inhibiting IL-1
      mediated effects involved in DIVD and LBP. In this study, the feasibility of ex
      vivo gene transfer of IL-1Ra to the IVD was investigated. Monolayer and alginate
      cultures of normal and degenerate human intervertebral disc (IVD) cells were
      infected with an adenoviral vector carrying the IL-1Ra gene (Ad-IL-1Ra) and
      protein production measured using an enzyme-linked immunosorbent assay. The
      ability of these infected cells to inhibit the effects of IL-1 was also
      investigated. In addition, normal and degenerate IVD cells infected with Ad-IL
      1Ra were injected into degenerate disc tissue explants and IL-1Ra production in
      these discs was assessed. This demonstrated that both nucleus pulposus and
      annulus fibrosus cells infected with Ad-IL-1Ra produced elevated levels of IL-1Ra
      for prolonged time periods, and these infected cells were resistant to IL-1. When
      the infected cells were injected into disc explants, IL-1Ra protein expression
      was increased which was maintained for 2 weeks of investigation. This in vitro
      study has shown that the use of ex vivo gene transfer to degenerate disc tissue
      is a feasible therapy for the inhibition of IL-1-mediated events during disc
      degeneration.

PMID- 16436112
TI  - Intraoral duct ligation without inclusion of the parasympathetic nerve supply
      induces rat submandibular gland atrophy.
AB  - The atrophic effect of ligating the main duct of the right submandibular gland
      was examined in rat using a novel intraoral approach that did not include the
      chorda lingual (CL) nerve. Comparison was made with the effect of duct ligation
      including the attached CL nerve as carried out in previous studies. In all
      animals, the contralateral, unligated left submandibular gland was used as a
      control. At different times (1, 2, 7, 14 and 21 days) after ligation, glands were
      removed and weighed. Tissue was fixed for morphological analysis and homogenized
      for biochemical assay of secretory proteins. After 21 days, ligated glands showed
      a significant decrease in wet weight compared with unligated glands. Weight loss
      was the greatest (P < 0.05) in glands ligated with the CL nerve included. Light
      microscopy revealed that following ligation, an initial inflammatory reaction was
      followed by severe atrophy of acini and granular ducts. The atrophy was less
      severe when the CL nerve was not ligated. Secretory proteins were decreased from
      day 1 onwards following duct ligation in both groups. It can be concluded that
      most of the atrophy induced by duct ligation is independent of damage caused to
      the parasympathetic nerve supply, although the latter causes a greater atrophy
      presumably due to denervation.

PMID- 16436109
TI  - Mouse models in non-alcoholic fatty liver disease and steatohepatitis research.
AB  - Non-alcoholic fatty liver disease (NAFLD) represents a histological spectrum of
      liver disease associated with obesity, diabetes and insulin resistance that
      extends from isolated steatosis to steatohepatitis and cirrhosis. As well as
      being a potential cause of progressive liver disease in its own right, steatosis
      has been shown to be an important cofactor in the pathogenesis of many other
      liver diseases. Animal models of NAFLD may be divided into two broad categories:
      those caused by genetic mutation and those with an acquired phenotype produced by
      dietary or pharmacological manipulation. The literature contains numerous
      different mouse models that exhibit histological evidence of hepatic steatosis
      or, more variably, steatohepatitis; however, few replicate the entire human
      phenotype. The genetic leptin-deficient (ob/ob) or leptin-resistant (db/db) mouse
      and the dietary methionine/choline-deficient model are used in the majority of
      published research. More recently, targeted gene disruption and the use of supra
      nutritional diets to induce NAFLD have gained greater prominence as researchers
      have attempted to bridge the phenotype gap between the available models and the
      human disease. Using the physiological processes that underlie the pathogenesis
      and progression of NAFLD as a framework, we review the literature describing
      currently available mouse models of NAFLD, highlight the strengths and weaknesses
      of established models and describe the key findings that have furthered the
      understanding of disease pathogenesis.

PMID- 16436111
TI  - A vitellogenic-like carboxypeptidase expressed by human macrophages is localized
      in endoplasmic reticulum and membrane ruffles.
AB  - Carboxypeptidase, vitellogenic-like (CPVL) is a serine carboxypeptidase of
      unknown function that was first characterized in human macrophages. Initial
      studies suggested that CPVL is largely restricted to the monocytic lineage,
      although it may also be expressed by cells outside the immune system. Here, we
      use a new monoclonal antibody to characterize the properties and localization of
      CPVL in human macrophages to elucidate a possible function for the protease. CPVL
      is up-regulated during the maturation of monocytes (MO) to macrophages, although
      the protein can be seen in both. In primary macrophages, CPVL is glycosylated
      with high mannose residues and colocalizes with markers for endoplasmic
      reticulum, while in MO it is more disperse and less clearly associated with
      endoplasmic reticulum. CPVL is highly expressed in lamellipodia and membrane
      ruffles, which also concentrate markers of the secretory pathway (MIP-1alpha and
      tumour necrosis factor-alpha) and major histocompatibility complex (MHC) class I
      and II molecules. CPVL can be seen on early latex bead and Candida albicans
      phagosomes, but it is not retained in the maturing phagosome, unlike MHC class
      I/II. CPVL has a mixed cytosolic and membrane-associated localization but is not
      detectable on the outer plasma membrane. We propose that CPVL may be involved in
      antigen processing, the secretory pathway and/or in actin remodelling and
      lamellipodium formation.

PMID- 16436113
TI  - Further development of a model of chronic bone marrow aplasia in the busulphan
      treated mouse.
AB  - Aplastic anaemia (AA) in man is an often fatal disease characterized by
      pancytopenia of the peripheral blood and aplasia of the bone marrow. AA is a
      toxic effect of many drugs and chemicals (e.g. chloramphenicol, azathioprine,
      phenylbutazone, gold salts, penicillamine and benzene). However, there are no
      widely used or convenient animal models of drug-induced AA. Recently, we reported
      a new model of chronic bone marrow aplasia (CBMA = AA) in the busulphan (BU)
      treated mouse: eight doses of BU (10.50 mg/kg) were administered to female BALB/c
      mice over a period of 23 days; CBMA was evident at day 91/112 post-dosing with
      significantly reduced erythrocytes, platelets, leucocytes and nucleated bone
      marrow cell counts. However, mortality was high (49.3%). We have now carried out
      a study to modify the BU-dosing regime to induce CBMA without high mortality, and
      investigated the patterns of cellular responses in the blood and marrow in the
      post-dosing period. Mice (n = 64/65) were dosed 10 times with BU at 0 (vehicle
      control), 8.25, 9.0 and 9.75 mg/kg over 21 days and autopsied at day 1, 23, 42,
      71, 84, 106 and 127 post-dosing (n = 7-15); blood and marrow samples were
      examined. BU induced a predictable bone marrow depression at day 1 post-dosing;
      at day 23/42 post-dosing, parameters were returning towards normal during a
      period of recovery. At day 71, 84, 106 and 127 post-dosing, a stabilized, late
      stage, nondose-related CBMA was evident in BU-treated mice, with decreased
      erythrocytes, platelets and marrow cell counts, and increased MCV. At day 127
      post-dosing, five BU-treated mice showed evidence of lymphoma. In this study,
      mortality was low, ranging from 3.1% (8.25 mg/kg BU) to 12.3% (9.75 mg/kg BU). It
      is concluded that BU at 9.0 mg/kg (or 9.25 mg/kg) is an appropriate dose level to
      administer (10 times over 21 days) to induce CBMA at approximately day 50-120
      post-dosing.

PMID- 16436117
TI  - The eel immune system: present knowledge and the need for research.
AB  - The European eel, Anguilla anguilla, is one of the most important warm water fish
      species cultured in southern Europe and the Mediterranean as well as in northern
      countries including Germany, the Netherlands and Denmark. The Japanese eel, A.
      japonica, is an important cultured fish in several Asiatic countries including
      Japan, China and Taiwan. During recent decades, research has been performed to
      elucidate the immune response of these species against different pathogens
      (viruses, bacteria or parasites). Nevertheless, there is very limited information
      in terms of both cellular and humoral immune responses. This review summarizes
      the present knowledge relating to the eel immune system and includes new data.

PMID- 16436115
TI  - Cyclooxygenase-2 expression and effect of celecoxib in flurothyl-induced neonatal
      seizure.
AB  - Endogenous PGE(2) dynamically regulates membrane excitability, synaptic
      transmission and plasticity. Neonatal seizures are associated with a number of
      activity-dependent changes in brain development including altered synaptogenesis
      and synaptic plasticity as well as reduction in neurogenesis. Thus, it is
      reasonable to hypothesize that alteration of cyclooxygenase-2 (COX-2) expression
      induced by neonatal seizure may influence brain development. We evaluated the
      expression of COX-2 and microsomal prostaglandin E synthase (mPGES) by Western
      blot analysis and immnohistochemistry in flurothyl-induced neonatal seizure and
      also studied the effect of celecoxib on seizure induction. Seven to 10 days old
      Sprague-Dawley rats were used for control (n = 18) and experimental group (n =
      30). Recurrent seizure group showed more increased level of COX-2 expression than
      control group. However, the level of mPGES-2 expression was similar in both
      groups, and mPGES-1 was not detected. Hippocampus of control rats showed
      endogenous COX-2 expression, which was localized mainly in CA3 region. This
      localization pattern was similar in recurrent seizure rats, but intensity of COX
      2 expression was more increased than in control rats. Celecoxib treatment
      significantly delayed the seizure attack and also reduced COX-2 expression. In
      conclusion, this study suggests that COX-2 expression is related to
      epileptogenesis in flurothyl-induced neonatal seizure model and shows the
      possibility that its inhibition lessens functional impairments that occurred in
      neonatal seizure.

PMID- 16436114
TI  - Early and late immunohistochemical and ultrastructural changes associated with
      functional impairment of the lachrymal gland following external beam radiation.
AB  - The aim of this study was to investigate scintigraphic, immunohistological and
      ultrastructural changes associated with radiation-induced dysfunction of the
      lachrymal gland in an established experimental animal model. Ten rabbits were
      randomized into two groups and used for the study; in the control as well as
      experimental group, the Schirmer-test, lachrymal gland scintigraphy, and
      immunohistological and ultrastructural investigations were carried out prior to
      irradiation and 72 h as well as 1 month after single-dose irradiation with 15 Gy.
      Seventy-two hours after irradiation, secretion reduction evaluated by the
      Schirmer-test was evident. At this phase, we could observe a decrease in the
      expression of alpha-SMA and a re-distribution of tenascin-C matrix.
      Ultrastructural changes of acinar and myoepithelial cells were noticed;
      simultaneously, disturbance in the primary (99m)TcO(4)- uptake as well as
      significant reduction of the lachrymal ejection fraction was assessed
      scintigraphically. These changes were still evident 1 month following irradiation
      but became less intensive. Single-dose irradiation with 15 Gy implicates a
      functional impairment of the lachrymal gland, which is associated with early
      immunohistological and ultrastructural alterations. These changes may represent
      objective surrogate parameters for radiogenic dysfunction and prerequisites for
      further investigations on radioprotection of lachrymal glands during radiotherapy
      of the periorbital region.

PMID- 16436118
TI  - Evidence of enhanced bacterial invasion during Diplostomum spathaceum infection
      in European grayling, Thymallus thymallus (L.).
AB  - Farmed grayling, Thymallus thymallus (L.), are susceptible to atypical Aeromonas
      salmonicida (aAS) infections. Interactions between bacteria and parasites were
      studied using grayling subjected to concomitant exposure to aAS bacteria and the
      digenean parasite Diplostomum spathaceum. Atypical AS was detected from fish by a
      combination of bacterial cultivation and polymerase chain reaction techniques. A
      detection level of 17 aAS cells per 100 mg intestine tissue sample was obtained.
      Concomitant bacterial exposure did not enhance the severity of grayling eye
      rupture and nuclear extrusion induced by D. spathaceum, but D. spathaceum
      invasion into grayling increased the proportion of fish carrying aAS in their
      heart tissue. However, the number of aAS cells detected in heart tissue was low.
      Atypical AS did not cause acute disease or mortality during 15 days post
      exposure. There was a higher prevalence of aAS in grayling heart samples than in
      intestinal samples, indicating that the intestine is not favoured by aAS. We
      suggest that heart tissue would be a good organ from which to isolate aAS when
      tracing latent carrier fish. We conclude that penetrating diplostomids can
      enhance bacterial infections in fish and that diplostomids can cause serious eye
      ruptures in grayling.

PMID- 16436119
TI  - Pathology of Edwardsiella tarda infection in turbot, Scophthalmus maximus (L.).
AB  - Macroscopic and histopathological changes in cultured turbot, Scophthalmus
      maximus (L.), in Spain caused by infection with Edwardsiella tarda are described.
      Eye tumefaction, inflammation, haemorrhages, ascites and the presence of a
      purulent fluid were the main macroscopic lesions observed. Histopathological
      lesions were found in the kidney, spleen and liver. In the kidney and spleen
      these were characterized by a severe apostematous inflammatory reaction, with a
      large number of abscesses. The liver was affected to a lesser degree and only
      some phagocytes loaded with bacteria were observed. Ultrastructural observations
      indicated that macrophages were the main cell type implicated in the inflammatory
      response. Most of the bacteria observed within the phagocyte cytoplasm showed no
      degenerative changes and some were dividing. Degenerative changes observed in
      macrophages indicate their failure in preventing the infection.

PMID- 16436120
TI  - Dietary beta-1,3 glucan potentiates innate immunity and disease resistance of
      Asian catfish, Clarias batrachus (L.).
AB  - This study investigated the effects of short and prolonged administration of a
      yeast beta-glucan on non-specific immune parameters, growth rate and the disease
      resistance of Asian catfish, Clarias batrachus. Fish fed with a basal diet
      (control) and test diet (basal diet supplemented with 0.1% glucan) for 1, 2 and 3
      weeks were assayed for superoxide production, serum myeloperoxidase (MPO)
      content, natural haemagglutinin level, complement and lysozyme activities. Fish
      were weighed at weekly intervals and specific growth rate (SGR, % increase in
      body weight per day) was determined. After each week, fish were challenged with
      Aeromonas hydrophila to measure the level of protection. Results showed that
      glucan administration at 0.1% in feed, significantly (P<0.05) enhanced MPO and
      lysozyme levels, superoxide production, haemagglutination titre and level of
      protection against A. hydrophila challenge, irrespective of length of exposure.
      The alternative complement activity and SGR were not affected by the dietary
      supplementation of yeast glucan. As glucan feeding at 0.1% for 1 week is able to
      enhance the non-specific immunity and disease resistance of catfish efficiently,
      short-term feeding might be used in farmed catfish diets to enhance disease
      resistance.

PMID- 16436121
TI  - Systematic position of copepods of the genus Achtheres (Crustacea: Copepoda:
      Siphonostomatoida) parasitizing perch, Perca fluviatilis L., and zander, Sander
      lucioperca (L.).
AB  - Parasitic copepods of the genus Achtheres commonly infect perch, Perca
      fluviatilis, and zander, Sander lucioperca, in Europe. The aim of this study was
      to verify the specific identity of these copepods. The parasites were examined
      morphologically, biometrically and genetically. Statistical processing of the
      biometrical data was based on both empirical measurements and transformed data
      related to total length and genital trunk width. Principal component analysis was
      applied to both sets of data. DNA of both parasite 'forms' was amplified using
      two sets of primers (EU5.8S+EU18S and 18SF1+28SR) and the products were subjected
      to restriction fragment length polymorphism (RFLP). Morphological differences
      were found in the overall shape of the copepod bodies as well as in the details
      of the armament of some appendages. The morphometric study emphasized the
      importance of second maxillae and genital process as the variables most
      distinctly distinguishing the two 'forms'. The two 'forms' of Achtheres differed
      in the DNA sequence amplified by one set of primers. RFLP revealed even more
      extensive differences between these two copepods. We concluded that the copepods
      parasitizing perch should be referred to as Achtheres percarum von Nordmann,
      1832, whereas a long-forgotten name, A. sandrae Gadd, 1901, should be applied to
      the copepods from zander.

PMID- 16436122
TI  - Factors affecting the intensity of epidermal papillomatosis in populations of
      roach, Rutilus rutilus (L.), estimated as scale coverage.
AB  - Studies of epidermal papillomatosis in fish populations have only rarely focused
      on the intensity of the disease, i.e. the number and size of papillomas.
      Furthermore, the methods used to evaluate the intensity of papillomatosis have
      not been standardized. We tested the reliability of a method based on counting of
      scales covered by papilloma tumours in roach, Rutilus rutilus (L). In addition,
      we studied the frequency distributions of the number of scales covered by
      papillomas within populations, evaluated the correlation between the prevalence
      and mean intensity of the disease among populations and examined the intensity of
      papillomatosis in roach with respect to sex and size of fish. Reliability of the
      scale coverage method was high. Therefore, the method could offer an effective
      way to determine the intensity of papillomatosis in fish species with large
      scales. The frequency distribution of the scale coverage of papillomas was highly
      aggregated within all populations studied. The mean intensity of papillomatosis
      increased with the size of the fish and was higher in males than in females.
      However, there was no correlation between the mean intensity and prevalence of
      the disease among the 19 roach populations studied.

PMID- 16436123
TI  - Skin expression of IL-1beta in East Atlantic salmon, Salmo salar L., highly
      susceptible to Gyrodactylus salaris infection is enhanced compared to a low
      susceptibility Baltic stock.

PMID- 16436125
TI  - Response to hepatitis A vaccine in HIV-positive patients.
AB  - The USPHS/IDSA guidelines for Prevention of Opportunistic Infections in Persons
      with human immunodeficiency virus (HIV) recommends that all susceptible HIV+
      patients at increased risk for hepatitis A virus (HAV) or with chronic liver
      disease, be vaccinated against HAV. Immune response to HAV vaccine has not been
      well studied in HIV+ patients. In particular, there is little information in the
      literature regarding the effect and relationship of the CD4 count and the immune
      response in HIV patients. A retrospective analysis of HIV+ patients who received
      HAV vaccine was performed, and the antibody response to HAV (anti-HAV) measured.
      Univariate and multivariate analyses were performed to determine predictors of
      response to vaccine administration. Of the 503 patients evaluated, 138 patients
      completed their HAV vaccination series and 48% of them had postvaccine anti-HAV
      positive results (responders). There was no difference in age, race,
      antiretroviral therapy use, or hepatitis C virus exposure between responders and
      nonresponders. In univariate analysis, responders were more likely to be female
      (40.3%vs 21.1%, P = 0.01), have a higher CD4 count at vaccine (508.6 cells/mm3 vs
      344.3 cells/mm3, P = 0.001) and marginally lower viral load at vaccine (2.65 log
      copies vs 2.94 log copies, P = 0.07). Multivariate analysis showed that female
      gender and higher CD4 count at vaccine were independent predictors of response to
      vaccine. Forty-eight per cent of our HIV+ patients responded to HAV vaccine
      administration. This is much lower than reported rates of 100% in HIV-negative
      patients. Female gender and CD4 count at vaccine, but not CD4 nadir, predicted
      response to vaccine.

PMID- 16436124
TI  - Hepatitis C and steatosis: a reappraisal.
AB  - The overall prevalence of steatosis in patients with Hepatitis C virus (HCV)
      chronic infection is 55.5% (range 34.8-81.2%). This is a two to threefold
      increase compared with the prevalence of steatosis in chronic hepatitides because
      of other aetiologies and of the figures expected on the grounds of a steatosis
      HCV chance association. HCV genotype 3 (HCV-3) has specific epidemiological
      features; furthermore, as compared with HCV-non-3 genotypes, it is associated
      with a higher prevalence (74.1%vs 47.9%, P < 0.01) and with more severe grades of
      steatosis (prevalence of grade 3 steatosis 29.6 vs 5.5 P < 0.01). Host and viral
      factors play a role, although to a variable extent, in the pathogenesis of HCV-3
      and non-3 steatosis. HCV load and body mass index are associated with steatosis
      in HCV-3 and in HCV-non-3 patients respectively. Serum cholesterol levels and
      liver steatosis at baseline follow an inverse relationship in HCV infection. As
      hypocholesterolaemia corrects only in those sustained responders to antiviral
      treatment both in genotype 3 and in non-3 genotypes, the occurrence of a virally
      induced, acquired and reversible hypobetalipoproteinaemia seems plausible.
      Steatosis affects the natural course of HCV infection: it is associated with
      fibrosis, a possible mediator of increased risk to develop type 2 diabetes, it
      impairs the response to antiviral treatment in HCV-3 patients and might
      constitute a risk factor for the development of hepatocellular carcinoma. These
      observations indicate the need to evaluate the efficacy of combined antiviral and
      'metabolic' approaches vs standard antiviral regimes in patients with steatosis
      and HCV chronic infection.

PMID- 16436127
TI  - Quantitative HBV DNA levels as an early predictor of nonresponse in chronic HBe
      antigen positive hepatitis B patients treated with interferon-alpha.
AB  - To reduce unnecessary exposure to treatment, physicians must decide at an early
      stage whether continuation of treatment has a reasonable chance of success for
      the individual patient. The objectives of our study were to evaluate the
      previously described quantitative hepatitis B e antigen (HBeAg) measurements vs
      quantitative hepatitis B virus (HBV) DNA measurements for prediction of
      nonresponse and response in interferon (IFN)-alpha treated HBeAg positive chronic
      HBV patients. Serum HBV DNA and HBeAg levels were assessed at baseline and weeks
      8 and 12. For each test (HBV DNA level at baseline, HBV DNA decrease between
      baseline and weeks 8 and 12, or the combination of these two, as well as HBeAg
      level at baseline, HBeAg decrease between baseline and weeks 8 and 12, and the
      combination of these two), we calculated the positive predictive value, negative
      predictive value, sensitivity and specificity. Monitoring with quantitative HBV
      DNA levels (area under ROC 0.87) was superior to monitoring with quantitative
      HBeAg levels (0.76, P < 0.05). Step-wise logistic regression identified HBV DNA
      at baseline and decrease in HBV DNA from baseline to week 12, as independent
      predictors of response. The overall test performance of predicting nonresponse
      (predictive value 100%) was best for log HBV DNA testing at week 12 compared with
      testing at week 8 due to a better prediction of sustained response (46%vs 38%)
      and lower misidentification of nonresponse (39%vs 54%). This study showed that
      quantitative HBV DNA testing at baseline in combination with a decrease between
      baseline and week 12 has a high predictive value for identifying patients who
      have virtually no chance of reaching a sustained response with IFN therapy.

PMID- 16436126
TI  - Correlation between translation efficiency and outcome of combination therapy in
      chronic hepatitis C genotype 3.
AB  - Combination therapy with interferon-alpha (IFN-alpha) and ribavirin (RBV) in
      chronic hepatitis C demonstrates the best responses against hepatitis C virus
      (HCV) of genotype 3. Still, it has proven to be ineffective in 20-30% of patients
      infected with this genotype. In the present study, we analysed the translation
      efficiency mediated by the internal ribosome entry site (IRES) region in HCV
      genotype 3 genomes isolated from sustained responders (SR) and non-responders
      (NR), assuming that this may influence the outcome of treatment. Pretreatment
      isolates of genotype 3 from 22 individuals (15 SR, seven NR) were selected for
      such analyses. The IRES region [nucleotide (nt) 1-407] was cloned into a dual
      luciferase vector and IRES activity assessed following transfection into various
      cell lines. Low relative translation efficiency was observed for IRES elements
      derived from SR patients, whereas those of NR patients showed significantly
      greater translation efficiency (29.7 +/- 13 vs 69.4 +/- 22; P < 0.01).
      Subsequently, the effect of IFN-alpha plus RBV on IRES-driven translation in
      vitro was determined. A greater suppressive effect was observed on IRES activity
      isolated from seven SR patients, when compared with seven NR patients. In
      conclusion, IRES efficiency in vitro correlated with treatment response for HCV
      genotype 3. Further studies are warranted to investigate whether IRES efficiency
      in vitro, or sequence motifs associated with IRES efficiency, will be worthwhile
      to explore as prognostic tools for other HCV genotypes in the treatment of
      chronic HCV infection.

PMID- 16436128
TI  - Genetic similarity of hepatitis C virus and fibrosis progression in chronic and
      recurrent infection after liver transplantation.
AB  - The effect of hepatitis C virus (HCV) genetic heterogeneity on clinical features
      of post-transplantation hepatitis C is controversial. Different regions of the
      HCV genome have been associated with apoptosis, fibrosis, and other pathways
      leading to liver damage in chronic HCV infection. Besides, differences in
      immunodominant regions, such as NS3, may influence HCV-specific immune responses
      and disease outcome. In the liver transplant setting, a recent study has reported
      a positive association between HCV-1b Core region genetic relatedness 5-year post
      transplantation and histological severity of recurrent hepatitis C. We have
      compared nucleotide sequences of HCV Core, NS3 and NS5b regions in HCV-1b
      infected patients 3 years post-transplantation (n = 22). A cohort of
      nontransplanted patients (n = 22) was used as control of natural chronic HCV-1b
      infection. Histological evaluation was used to define the rate of fibrosis
      progression. Molecular variance analysis did not show significant differences in
      HCV sequences between transplanted and nontransplanted patients, or between those
      with fast or slow fibrosis progression. The same results were obtained when
      analysing phylogenetic trees for Core, NS3 and NS5b regions. A more appropriate
      clustering method (using minimum spanning networks) revealed a significant
      positive relationship between HCV genetic similarity in Core (r = 0.550, P <
      0.01) and NS5b regions (r = 0.847, P < 0.01) and the yearly rate of fibrosis
      progression in nontransplanted patients which, in contrast, was not observed in
      transplanted patients. Our results indicate that some strains of HCV-1b might be
      more pathogenic in the natural course of chronic infection by this virus subtype.
      In the liver transplant setting, when the immune response is severely
      compromised, other mechanisms are probably more important in determining
      hepatitis C progression.

PMID- 16436129
TI  - Ethnic differences in the presentation of chronic hepatitis C.
AB  - Hispanics comprise 13% of the population in the United States and are the fastest
      growing minority group. Features of hepatitis C in Hispanics have not been well
      characterized. The aims of this study were to compare features of hepatitis C
      among Hispanics, Whites, and African-Americans and to characterize hepatitis C
      infection in Hispanics. A retrospective analysis was performed on 1225
      consecutive patients with hepatitis C seen at the University of Illinois at
      Chicago including 227 Hispanics, 508 Whites, and 490 African-Americans. Data
      collection consisted of demographic variables, risk factors for hepatitis C,
      history of alcohol use, laboratory parameters and liver histology. Pair-wise
      comparisons showed that Hispanics had higher aminotransferase levels than Whites
      and African-Americans. Hispanics had higher portal inflammation scores on liver
      biopsy than African-Americans (P = 0.002) and Whites (P = 0.043). Hispanics had a
      higher frequency of cirrhosis than African-Americans (P < 0.001) and a trend
      towards more cirrhosis than Whites (P = 0.165). There was a trend towards a
      higher prevalence of cirrhosis in Hispanic women (56%) than in Hispanic men (45%)
      [P = 0.14]. A cross-sectional analysis of patients at our liver center showed
      that Hispanics with hepatitis C had higher aminotransferase levels, more portal
      inflammation than Whites and African-Americans, and a higher prevalence of
      cirrhosis than African-Americans.

PMID- 16436130
TI  - Do antiviral CD8+ T cells select hepatitis C virus escape mutants? Analysis in
      diverse epitopes targeted by human intrahepatic CD8+ T lymphocytes.
AB  - Hepatitis C virus (HCV) is a variable RNA virus that can readily establish
      persistent infection. Cellular immune responses are important in the early
      control of the virus. Evidence from animal models suggests that mutation in
      epitopes recognized by CD8+ T lymphocytes may play an important role in the
      establishment of persistence but in human persistent infection, equivalent
      evidence is lacking. We investigated this by analysing a unique resource: viruses
      from a set of chronically HCV-infected individuals in whom the CD8+ T-cell
      responses in liver had previously been accurately mapped. Virus was sequenced in
      seven individuals at 10 epitopes restricted by 10 human leucocyte antigen (HLA)
      molecules. Two main patterns emerged: in the majority of epitopes sequenced, no
      variation was seen. In three epitopes, mutations were identified which were
      compatible with immune escape as assessed using phylogenetic and/or functional
      studies. These data suggest that - even where specific intrahepatic T cells are
      detectable - many epitopes do not undergo mutation in chronic human infection. On
      the contrary, virus may escape from intrahepatic CD8+ T-cell responses in a
      'patchy' manner in certain specific epitopes. Furthermore, longitudinal studies
      to identify the differences between 'selecting' and 'nonselecting' intrahepatic
      CD8+ T-cell responses are needed in HCV infection.

PMID- 16436131
TI  - Cleavage of intracellular hepatitis C RNA in the virus core protein coding region
      by deoxyribozymes.
AB  - Hepatitis C virus (HCV) infection represents an important global health problem.
      Current antiviral therapeutics for HCV have proven inadequate in stemming the
      disease process. A novel therapeutic strategy involves the use of deoxyribozymes,
      also known as DNA enzymes or DNAzymes. These catalytic DNA molecules, designed to
      target and cleave specific RNA sequences, have shown promise in in vitro
      experimental models for various diseases and may serve as an alternative or
      adjunct to current HCV drug therapy. We designed and tested several
      deoxyribozymes that can bind and cleave highly conserved RNA sequences encoding
      the HCV core protein in in vitro systems. One of these deoxyribozymes reduced the
      level of our HCV RNA target by 32% and 48% after 24 h of cell exposure when
      tested in human hepatoma and epithelial cell lines, respectively. As this
      deoxyribozyme showed significant cleavage activity against HCV core protein
      target RNA in human cells, it may have potential as a therapeutic candidate for
      clinical trial in HCV infected patients.

PMID- 16436133
TI  - Basophils and mast cells at the centre of the immunological response.

PMID- 16436132
TI  - Pilot study of interferon-alpha-ribavirin-interleukin-2 for treatment of
      nonresponder patients with severe liver disease infected by hepatitis C virus
      genotype 1.
AB  - The aim of this randomized prospective study was to assess the efficacy and
      safety of a triple therapy with interferon-alpha (IFN-alpha)-ribavirin
      interleukin-2 (IL-2) for the treatment of patients with genotype 1 infection and
      high viral load nonresponsive to primary IFN-ribavirin therapy. Twenty hepatitis
      C virus (HCV) genotype 1 patients with high viral load and Metavir fibrosis score
      >or=2 without HIV co-infection who were previously nonviral responders to
      standard treatment with IFN plus ribavirin were intensively re-treated with IFN
      alpha2a (3 millions (M) IU every 2 days) combined with ribavirin (1000-1200
      mg/day) for a 24-week period. Patients were randomized to receive four cycles of
      subcutaneous injection of IL-2 (3 MIU/day, 5 days a week every 3 weeks) during
      either the first 12 weeks (group 1, n = 10) or the last 12 weeks (group 2, n =
      10) of combination therapy. At the end of triple therapy, six patients (30%)
      achieved a biochemical response and 4 (20%) a viral response followed by a
      relapse after triple therapy withdrawal. After 12 weeks of therapy, no difference
      in viral load was observed between the groups. The decrease in viral load in
      group 2 was not raised after the addition of IL-2 to IFN plus ribavirin
      combination therapy. No serious adverse effects were observed. In conclusion, in
      patients with poor predictive factors of response, the addition of IL-2 to IFN
      ribavirin combination therapy does not exert a favourable impact on HCV
      treatment.

PMID- 16436134
TI  - Identification of tryptase- and chymase-related gene clusters in human mast cells
      using microarrays.
AB  - Tryptase and chymase are the two major granular proteases present in human mast
      cell (MC)s. We used oligonucleotide microarray to measure the levels of
      approximately 22,000 transcripts in cord blood-derived MCs at 4 weeks, 8 weeks,
      12 weeks and 18 weeks in culture. Tryptase (TPSB2) was expressed at the highest
      level among all transcripts and its expression level reached a plateau at 8
      weeks. On the other hand, the expression level of chymase (CMAI) doubled every 4
      6 weeks. A similar tendency was found at the protein levels with FACS analysis.
      After filtering the transcripts with MC-specificity, hierarchical clustering
      analysis identified 494 and 81 transcripts in the same clusters with tryptase and
      chymase, respectively. MC-specific genes, KIT and HDC were found in the tryptase
      cluster. In the chymase cluster, a critical suppressor for cell senescence, BMI1
      and the several related genes were found, suggesting that chymase expression may
      be closely related to cell senescence/quiescence events.

PMID- 16436135
TI  - Effects of various statins on cytokine-dependent growth and IgE-dependent release
      of histamine in human mast cells.
AB  - BACKGROUND: Statins are inhibitors of hydroxymethylglutaryl coenzyme A (HMG CoA)
      reductase, a key enzyme in mevalonic acid (MVA)-dependent signaling. Recent data
      suggest that statins exhibit profound inhibitory effects on growth and function
      of various immune cells. In the present study, we examined the in vitro effects
      of five different statins on primary human mast cells (MCs), MC progenitors, and
      the human MC line HMC-1. METHODS: Histamine release experiments were conducted on
      isolated MCs using statins and an anti-immunoglobulin E (IgE) antibody. Culture
      experiments were performed with stem cell factor (SCF) and interleukin (IL)-6,
      and cord blood-derived progenitors. RESULTS: Preincubation of primary lung MCs
      with cerivastatin or atorvastatin (1-50 microM) for 24 h resulted in inhibition
      of anti-IgE-induced release of histamine. The effects of both statins were dose
      dependent. Moreover, both statins, and to a lesser degree lovastatin, were found
      to inhibit the SCF-induced differentiation of MCs from their progenitors. The
      other statins tested (simvastatin, pravastatin) did not affect mediator release
      or growth of MCs. CONCLUSIONS: Cerivastatin and atorvastatin act as inhibitors of
      growth and function of human MCs.

PMID- 16436136
TI  - Molecular mechanisms for the release of chemokines from human leukemic mast cell
      line (HMC)-1 cells activated by SCF and TNF-alpha: roles of ERK, p38 MAPK, and NF
      kappaB.
AB  - BACKGROUND: Mast cells play pivotal roles in IgE-mediated airway inflammation and
      other mast cell-mediated inflammation by activation and chemoattraction of
      inflammatory cells. OBJECTIVE: We investigated the intracellular signaling
      mechanisms regulating chemokine release from human mast cell line-1 (HMC-1) cells
      activated by stem cell factor (SCF) or tumor necrosis factor (TNF)-alpha.
      METHODS: Chemokine gene expressions were assessed by reverse transcription
      polymerase chain reaction, while the releases of chemokines were determined by
      flow cytometry or enzyme-linked immunosorbent assay (ELISA). To elucidate the
      intracellular signal transduction regulating the chemokine expression,
      phosphorylated-extracellular signal-regulated kinase (ERK), phosphorylated-p38
      mitogen-activated protein kinase (MAPK) and nuclear translocated nuclear factor
      (NF)-kappaB-DNA binding were quantitatively assessed by ELISA. RESULTS: Either
      SCF or TNF-alpha could induce release from HMC-1 cells of interleukin (IL)-8,
      monocyte chemoattractant protein (MCP)-1, regulated upon activation normal T-cell
      expressed and secreted (RANTES), and I-309, while SCF and TNF-alpha induced
      release of macrophage inflammatory protein (MIP)-1beta and interferon-gamma
      inducible protein-10 (IP-10), respectively. Using various selective inhibitors
      for signaling molecules, we found that the inductions of IL-8, MCP-1, and I-309
      were mediated by either SCF-activated ERK or TNF-alpha-activated p38 MAPK, while
      the induction of IP-10 by TNF-alpha was mediated by both activated p38 MAPK and
      NF-kappaB. The induction of RANTES by SCF or TNF-alpha was mediated by ERK and NF
      kappaB, respectively, and SCF induced MIP-1beta release was mediated by ERK.
      CONCLUSION: The above results therefore elucidated the different intracellular
      signaling pathways regulating the release of different chemokines from SCF and
      TNF-alpha-activated mast cells, thereby shedding light for the immunopathological
      mechanisms of mast cell-mediated diseases.

PMID- 16436137
TI  - Basophil allergen threshold sensitivity: a useful approach to anti-IgE treatment
      efficacy evaluation.
AB  - BACKGROUND: Monitoring of the allergen sensitivity of a patient is most important
      for optimal patient care and a basic prerequisite for immunomodulating treatment.
      The objective of this study was to investigate how basophil allergen sensitivity
      can be applied in the monitoring of anti-immunoglobulin E (IgE) treatment.
      METHODS: Basophils from timothy grass pollen allergic patients were, by flow
      cytometry, analysed for allergen threshold sensitivity (CD-sens) by measuring
      CD63 up-regulation on CD203c-identified basophils. The results were compared with
      maximal percentage CD63 up-regulation at one allergen dose (CD-max), skin prick
      test end-point allergen titration, (SPT-sens), nasal provocation titration tests
      (nasal provocation titre) and serum IgE and IgE antibody concentrations. RESULTS:
      There was a significant correlation (r = 0.50, P = 0.01) between CD-sens and SPT
      sens, CD-sens and the IgE antibody concentration in percentage of 'total IgE'
      (relative IgE antibody concentration) (r = 0.72, P < 0.001) as well as between CD
      sens and nasal provocation titre (r = 0.54, P < 0.05) but, in contrast, CD-max
      did not correlate with any of the sensitization parameters, i.e. SPT-sens, nasal
      provocation titre, absolute and relative IgE antibody concentration or CD-sens.
      CD-sens could be used to monitor omalizumab treatment efficacy while, based on CD
      max, four of seven symptom-free patients on omalizumab would have been classified
      as having ongoing allergy. CONCLUSIONS: CD-sens seems to be very useful for the
      determination of a patient's allergen sensitivity and should be evaluated for the
      measurement and monitoring of anti-IgE treatment efficacy. CD-max, the
      conventional approach to basophil allergen challenge, which mirrors cell
      reactivity, gives incorrect information.

PMID- 16436138
TI  - Are basophil histamine release and high affinity IgE receptor expression involved
      in asymptomatic skin sensitization?
AB  - BACKGROUND: Immunoglobulin (Ig)E-sensitized persons with positive skin prick
      test, but no allergy symptoms, are classified as being asymptomatic skin
      sensitized (AS). The allergic type 1 disease is dependant on IgE binding to the
      high affinity IgE-receptor (FcepsilonRI) expressed on basophils and mast cells.
      However, a relationship between the AS status and FcepsilonRI has not been
      investigated. We aimed to characterize basophils from AS by looking at histamine
      release (HR) (sensitivity and reactivity) and the FcepsilonRI molecule, and
      compare it with nonatopic (NA) or allergic (A) persons. METHODS: Blood was
      obtained from NA (n = 14), grass and/or birch A persons (n = 17) and mono
      sensitized grass or birch pollen AS (n = 12). The basophil sensitivity and
      reactivity were examined by anti-IgE triggered HR. Surface expression of
      FcepsilonRI and IgE were measured by flow cytometry, FcepsilonRIalpha protein was
      identified using a radioimmunoassay and Western blot. mRNA coding for the classic
      FcepsilonRIbeta-chain and the truncated form (FcepsilonRIbetaT) were determined
      by real-time PCR. RESULTS: The AS group was less reactive than NA or A persons
      when triggered by anti-IgE and had a significant higher number of nonresponders.
      However, there was no difference in sensitivity among the three groups and
      furthermore; the groups did not vary in FcepsilonRI- and IgE-surface expression,
      FcepsilonRIalpha-protein level or beta/betaT ratio. CONCLUSION: Basophils from AS
      persons are less reactive and include more nonresponders than basophils from NA
      and A persons, but do not differ regarding the FcepsilonRI molecule.

PMID- 16436139
TI  - Diagnosis of neuromuscular blocking agent hypersensitivity reactions using
      cytofluorimetric analysis of basophils.
AB  - BACKGROUND: Immunoglobulin E (IgE)-mediated hypersensitivity reactions to
      neuromuscular blocking agents (NMBA) are common and life threatening. Basophil
      activation based upon the expression of CD63 in the presence of specific
      allergens was found to be of importance for the diagnosis of IgE-mediated
      hypersensibility. METHODS: The Basotest was evaluated for the diagnosis of NMBA
      in 47 patients with proven NMBA anaphylaxis, 40 atopic subjects nonallergic to
      NMBA and five healthy volunteers. Diagnosis of NMBA was made according to
      international standards on clinical history, skin tests and provocation tests
      when needed. RESULTS: In the NMBA allergic patients, sensitivity of Basotest was
      36.1%, but it increased to 85.7% for reactions which occurred within the last 3
      years. The specificity was 93.3%. CONCLUSION: Basotest may be useful for the
      diagnosis of NMBA allergy in patients with a suspicion of recent IgE-mediated
      hypersensitivity reaction to NMBA.

PMID- 16436141
TI  - EAACI/GA2LEN/EDF guideline: management of urticaria.
AB  - This guideline is the result of a consensus reached during a panel discussion at
      the second International Consensus Meeting on Urticara, Urticaria 2004, a joint
      initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound
      impact on the quality of life, and effective treatment is therefore required. The
      recommended first line treatment are nonsedating H1 antihistamines. They have
      proven to be effective in double-blind controlled studies, but dosages increased
      up to fourfold over the recommended doses may be necessary. However, for
      different urticaria subtypes and in view of individual variation in the course of
      the disease and response to treatment, additional or alternative therapies may be
      required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not
      recommended for long-term treatment due to unavoidable severe adverse effects.
      This guideline was, in addition, accepted by the European Dermatology Forum (EDF)
      and formally approved by the European Union of Medical Specialists (UEMS).

PMID- 16436142
TI  - IgE sensitization, respiratory allergy symptoms, and heritability independently
      increase the risk of otitis media with effusion.
AB  - BACKGROUND AND AIMS: Epidemiological evidence examining the role of atopy and/or
      allergy in the pathogenesis of otitis media with effusion (OME) is inconclusive.
      The aim of this study was to assess any increased risk for OME attributable to
      allergy-related factors, in a well-characterized population using a case-control
      design and multivariate analysis. SUBJECTS AND METHODS: Eighty-eight 1-7-year-old
      children with OME, diagnosed by clinical and tympanometric evaluation and 80
      matched controls were enrolled. A standardized questionnaire was completed, in
      order to assess factors related to OME and allergy-related symptoms and diagnoses
      using strict clinical definitions. Specific IgE was measured by skin-prick tests
      and/or CAP-FEIA. RESULTS: The patient and control groups were well matched.
      Factors conferring increased risk for OME in the univariate analysis included IgE
      sensitization, dyspnea, wheezing, asthma, paroxysmal sneezing, rhinitis, eczema,
      'any allergic disease,' family history of otitis media, and family history of
      allergy. After multivariate analysis IgE sensitization, wheezing, nasal
      obstruction, family history of otitis, and child-care attendance remained as
      independent risk factors for development of OME. CONCLUSION: IgE sensitization
      and respiratory allergy symptoms are independent risk factors for the development
      of OME, suggesting that both immunological and mechanical pathways may contribute
      to the development of the disease. Otitis heritability provides additional risk,
      as well as frequent exposure to viral upper respiratory tract infections in
      children attending daycare. Treatment and/or prevention of OME using anti
      allergic medications should be further examined.

PMID- 16436140
TI  - EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of
      urticaria.
AB  - This guideline is the result of a consensus reached during a panel discussion at
      the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint
      initiative of the European Academy of Allergology and Clinical Immunology
      Dermatology Section and the European Union (EU)-funded network of excellence,
      GA2LEN. It covers the definition and classification of urticaria, taking into
      account the recent progress in identifying causes, eliciting factors and
      pathomechanisms of this disease. We have outlined useful diagnostic approaches
      for different subtypes of urticaria. This guideline was, in addition, accepted by
      the European Dermatology Forum (EDF) and was formally approved by the European
      Union of Medical Specialists (UEMS).

PMID- 16436143
TI  - ImmunoCAP Phadiatop Infant--a new blood test for detecting IgE sensitisation in
      children at 2 years of age.
AB  - BACKGROUND: Correct diagnosis of immunoglobulin E (IgE)-mediated disease is the
      prerequisite for secondary allergy prevention during early childhood. OBJECTIVE:
      To evaluate the diagnostic efficacy of a new blood test, Phadiatop Infant, in
      detecting IgE sensitisation to food and inhalant allergens among children at 2
      years of age. METHODS: Children (n = 239) were followed prospectively from birth
      to 2 years of age for the presence of IgE sensitisation and the development of
      atopic manifestations. Immunoglobulin E sensitisation was evaluated by skin prick
      test (SPT) and analysis of allergen-specific IgE antibodies in plasma to food and
      inhalant allergens. The children were classified into three groups: IgE
      sensitised, non-IgE sensitised and inconclusive, depending on SPT and allergen
      specific IgE results. RESULTS: Twenty-six (11%) of the children were classified
      as IgE-sensitised, 182 (76%) as non-IgE sensitised and 31 (13%) as inconclusive.
      Phadiatop Infant was positive in 50 (21%) of the children. Ten children (4%) with
      identified IgE antibodies against the selected food and inhalant allergens showed
      negative Phadiatop Infant. Three children showed positive Phadiatop Infant but
      were negative in the other tests performed. These results correspond to positive
      and negative predictive values for Phadiatop Infant of 89 and 99%, respectively.
      Children with clinical symptoms of atopic diseases had significantly increased
      levels for Phadiatop Infant (P < 0.01). CONCLUSION: Phadiatop Infant appears to
      be a reliable alternative to SPT and the measurement of allergen-specific IgE
      antibodies in plasma for detecting clinically important IgE sensitisation among
      children at 2 years of age.

PMID- 16436144
TI  - Screening for allergic respiratory disease in the general population with the
      ADVIA Centaur Allergy Screen Assay.
AB  - BACKGROUND: In patients in whom the clinical indication for immunoglobulin E
      (IgE)-mediated allergic respiratory disease is weak, a single qualitative
      multiallergen-screening assay for IgE antibody to multiple allergen specificities
      may support the absence of IgE-mediated allergic respiratory disease. The aim was
      to investigate the diagnostic efficacy of a new multiallergen-screening assay in
      relation to skin prick test (SPT) reactivity and objective diagnoses of allergic
      respiratory disease in a general population setting. METHODS: A total of 709
      participants in a population-based study were examined by questionnaire and SPT.
      Serum was analysed by using a multiallergen-screening assay: the ADVIA Centaur
      Allergy Screen (AS) assay. The dichotomized result of the AS assay was compared
      with SPT reactivity, specific IgE positivity, and a clinical diagnosis of
      allergic rhinitis or allergic asthma defined by the presence of relevant symptoms
      and positive SPTs. RESULTS: Sensitivity, specificity, and positive (PPV) and
      negative predictive values (NPV) of the AS against SPT reactivity were 86%, 96%,
      94%, and 89%, respectively. A negative AS assay test was able to exclude allergic
      rhinitis and allergic asthma with a probability of more than 96% and 98% (NPV),
      respectively. The AS assay was able to identify more than 92% and 92%
      (sensitivity) of cases of allergic rhinitis and allergic asthma, respectively.
      CONCLUSIONS: The AS assay proved to be a valid measure of allergic respiratory
      disease and may be used as a screening tool to rule out allergic respiratory
      disease, and as an objective measure of allergic respiratory disease in
      epidemiological studies.

PMID- 16436146
TI  - Comparison of allergenicity and allergens between fish white and dark muscles.
AB  - BACKGROUND: Fish is one of the most frequent causes of immunoglobulin E (IgE)
      mediated food allergy. Although the fish dark muscle is often ingested with the
      white muscle, no information about its allergenicity and allergens is available.
      METHODS: Heated extracts were prepared from both white and dark muscles of five
      species of fish and examined for reactivity with IgE in fish-allergic patients by
      enzyme-linked immunosorbent assay (ELISA) and for allergens by immunoblotting.
      Cloning of cDNAs encoding parvalbumins was performed by rapid amplification cDNA
      ends. Parvalbumin contents in both white and dark muscles were determined by
      ELISA using antiserum against mackerel parvalbumin. RESULTS: Patient sera were
      less reactive to the heated extract from the dark muscle than to that from the
      white muscle. A prominent IgE-reactive protein of 12 kDa, which was detected in
      both white and dark muscles, was identified as parvalbumin. Molecular cloning
      experiments revealed that the same parvalbumin molecule is contained in both
      white and dark muscles of either horse mackerel or Pacific mackerel. Parvalbumin
      contents were four to eight times lower in the dark muscle than in the white
      muscle. CONCLUSIONS: The fish dark muscle is less allergenic than the white
      muscle, because the same allergen molecule (parvalbumin) is contained at much
      lower levels in the dark muscle than in the white muscle. Thus, the dark muscle
      is less implicated in fish allergy than the white muscle.

PMID- 16436145
TI  - Identification of oleosins as major allergens in sesame seed allergic patients.
AB  - BACKGROUND: The prevalence of sesame allergy is increasing in European countries.
      Cases of severe allergy lack any evidence of specific immunoglobulin (Ig)Es by
      prick tests and CAPSystem-FEIA. The reasons for this negativity are unknown.
      METHODS: In 32 patients displaying immediate symptoms such as anaphylactic shock,
      asthma, urticaria, angioedema, sesame allergy was diagnosed by double-blind
      placebo-controlled food challenge (DBPCFC) or convincing clinical history.
      However, 10 patients had negative prick tests and CapSystem-FEIA. The specificity
      of IgEs was further investigated by enzyme-linked immunosorbent assay (ELISA),
      isoelectrofocalisation (IEF)-blotting, and sodium dodecyl sulfate polyacrylamide
      gel electrophoresis (SDS-PAGE) blotting using total sesame extracts and purified
      fraction of oil bodies. Monospecific rabbit antibodies directed to two oleosin
      isoforms (15 and 17 kDa) were used. RESULTS: By ELISA, white sesame seed extract
      allowed the detection of higher levels of IgE than brown sesame extract. In all
      sera, numerous bands binding IgEs were detected by IEF or SDS-PAGE. In reducing
      conditions, two bands (15-17 kDa), could be separated from 2S albumin. Oleosins,
      present in oil bodies fractions, were recognized by IgEs from all sera.
      CONCLUSION: Oleosins are major allergens of sesame seeds and may be relevant to
      severe anaphylaxis. Falsely negative prick tests could be due to the lack of
      oleosins in presently available extracts, or to the fact that epitopes might be
      buried in the inner molecule. Detection tests currently used to identify sesame
      allergens based on sesame vicillins or other storage proteins could be
      insufficient for the detection of sesame seed contamination. Oleosins have been
      named Ses i 4 (17 kDa) and Ses i 5 (15 kDa), in accordance with the IUIS
      Nomenclature Committee.

PMID- 16436147
TI  - Strong allergic patch test reactions may indicate a general disposition for
      contact allergy.
AB  - BACKGROUND: Patch test patients have two or more positive reactions to unrelated
      allergens more often than to be expected by chance. This study evaluates
      synchronous patch test reactions to test the hypothesis that in such cases an
      allergen-independent disposition for contact sensitization may be involved.
      METHODS: Data of 87 834 patients tested with a standard patch test series in 42
      centers of a Central European Network were retrospectively evaluated. Analyses
      were done for synchronous positive reactions of graded strength to nickel
      sulfate, fragrance mix, and to those five allergens that followed in frequency of
      positive results. All seven allergens selected were not related by chemical
      structure or exposure. Descriptive univariate and bivariate analyses as well as a
      polytomous logistic regression analysis were performed. Odds ratios with 95%
      confidence intervals were calculated. RESULTS: With an increasing strength of a
      positive reaction to nickel or to fragrance mix the likelihood of further
      positive reactions to unrelated contact allergens increased significantly, and
      the mean strength of such additional reactions raised steadily with an increasing
      strength of a nickel or fragrance reaction. CONCLUSIONS: Our findings support the
      idea that patients who respond with a strong patch test reaction may have a
      particular general disposition to acquire contact sensitivity to additional
      unrelated allergens. They should therefore not only be advised to avoid their
      known allergen but in addition to minimize exposure other contact allergens.

PMID- 16436148
TI  - Acute allergic reactions in children with AEDS after prolonged cow's milk
      elimination diets.
AB  - BACKGROUND: Food allergy is not always correctly diagnosed in children with
      atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is
      not without danger. METHODS: After admission to our clinic, 11 children with a
      prolonged cow's milk (CM) elimination diet because of AEDS and sensitization
      underwent double-blind placebo-controlled food challenge (DBPCFC).
      Retrospectively, the exposure to CM, sensitization and reactions to accidental
      ingestion were carefully documented. The DBPCFC was used to evaluate the
      childrens' current status. RESULTS: Before the elimination period (median 2.3
      years; started before the admission) all 11 children with AEDS were sensitized
      and had ingested CM (four bottle-fed; seven breast-fed without CM diet of the
      mother) without the development of acute reactions. The diagnosis of CM allergy
      was not confirmed by DBPCFC previously. After elimination the AEDS had not
      improved, but nevertheless the diet was continued. During the elimination period,
      eight of 11 children developed severe acute allergic reactions to CM after
      accidental ingestion. In evaluation, in our clinic all 11 children experienced
      acute allergic reactions to CM during DBPCFC. CONCLUSION: There is a considerable
      chance of developing acute allergic reactions to CM after elimination in children
      with AEDS without previous problems after CM intake.

PMID- 16436150
TI  - Pen ch 13 allergen induces secretion of mediators and degradation of occludin
      protein of human lung epithelial cells.
AB  - BACKGROUND: Alkaline serine proteases from six prevalent airborne Penicillium and
      Aspergillus species have been identified as a group of major allergens (group
      13). After entering human airways, the allergens are in initial contacts with
      respiratory epithelial cells. The purpose of this study is to investigate
      interactions between the Pen ch 13 allergen from P. chrysogenum and human lung
      epithelial cells. METHODS: A549 cells, 16HBE14o- cells and primary cultures of
      human bronchial epithelial cells (HBEpC) were exposed to purified Pen ch 13 and
      mediators released into culture supernatants were assayed with enzyme-linked
      immunosorbent assay (ELISA) kits. Cleavage of occludin in 16HBE14o- cells was
      analysed by immunofluorescent staining of whole cells and immunoblot analysis of
      whole cell extracts. Fragments generated by incubating Pen ch 13 and a synthetic
      peptide carrying the occludin sequence were analysed by mass spectrometry.
      RESULTS: Pen ch 13 induced productions of prostaglandin-E2 (PGE2), interleukin
      (IL)-8 and transforming growth factor (TGF)-beta1 by A549 cells, 16HBE14o- cells
      and primary cultures of HBEpC. The protease activity of Pen ch 13 is needed for
      the induction of PGE2 IL-8, TGF-beta1 and cyclo-oxygenase (COX)-2 expression. A
      tight junction protein occludin of 16HBE14o- cells can be cleaved by Pen ch 13 at
      Gln202 and Gln211 which are within the second extracellular domain of the
      protein. CONCLUSION: Pen ch 13 may contribute to asthma by damaging the barrier
      formed by the airway epithelium and stimulating the release of mediators that
      orchestrate local immune responses and inflammatory process from HBEpC.

PMID- 16436149
TI  - Onset of pruritus relief with pimecrolimus cream 1% in adult patients with atopic
      dermatitis: a randomized trial.
AB  - BACKGROUND: Pimecrolimus cream 1% (Elidel, Novartis Pharmaceuticals AG)
      effectively improves/relieves pruritus associated with atopic dermatitis (AD),
      but few data are available regarding the timing of relief. The purpose of this
      study was to investigate the timing of pruritus relief produced with pimecrolimus
      in adults with mild/moderate AD and moderate/severe pruritus. METHODS: Patients
      were randomized to 7 days of treatment with pimecrolimus (n = 100) or vehicle (n
      = 98). Pruritus severity was assessed daily on a 4-point scale (0 = absent, 3 =
      severe), reflecting the previous 24 h experience. Patients who completed this
      core study were eligible to enter a voluntary 5-week, open-label extension study.
      RESULTS: A significant effect was noted within 48 h of treatment, with pruritus
      improving in 56% of pimecrolimus-treated patients and 34% of vehicle-treated
      patients (P = 0.003). Pruritus relief was maintained during the remainder of the
      core and extension phases, and was accompanied by an improvement in the
      Investigator's Global Assessment score. CONCLUSION: Pimecrolimus cream 1%
      significantly reduced pruritus within 48 h.

PMID- 16436151
TI  - Asthma patients are willing to use mobile and web technologies to support self
      management.

PMID- 16436152
TI  - Concurrent allergic diseases: a cross-sectional study in a French population.

PMID- 16436153
TI  - A case of occupational asthma and rhinitis caused by Sanyak and Korean ginseng
      dusts.

PMID- 16436154
TI  - Allergens of Ficus benjamina (weeping fig): unique allergens in sap.

PMID- 16436155
TI  - Three cases of occupational asthma induced by thiamphenicol: detection of serum
      specific IgE.

PMID- 16436157
TI  - Listening to the views of people affected by cancer about cancer research: an
      example of participatory research in setting the cancer research agenda.
AB  - AIM: The study 'Listening to the Views of People Affected by Cancer About Cancer
      Research' is currently exploring the views people affected by cancer have about
      cancer research and identifying their research priorities. Integral to this is
      the broader aim of ensuring an effective, collaborative participation of patients
      and carers in the design and conduct of the study. On the basis of experiences
      with the study to date, the latter is explored in this paper. DESIGN: The study
      adopts a 'participatory research' approach entailing the formation of a
      'reference group' and a subsequent patient and carer co-researcher group. Patient
      and carer members of these groups were identified through the patient forums of
      UK cancer networks and by approaching 'hard to reach' representatives directly
      through community groups and participating study sites. FINDINGS: Experiences
      from this study illustrate that a 'participatory research' approach is
      appropriate in engaging patients and carers in the research process. Establishing
      a group of people affected by cancer in the study was found to be particularly
      effective in enhancing the design and conduct of the research. CONCLUSIONS:
      'Participatory research' offers an effective means of involving patients and
      carers throughout the research process, thus strengthening the relevance and
      appropriateness of research findings and methods.

PMID- 16436158
TI  - The development of picture cards and their use in ascertaining characteristics of
      Chinese surgical patients' decision-making preferences.
AB  - AIM: This exploratory pilot study developed and tested the validity of picture
      cards as a strategy to ascertain patients' desired participation in decision
      making. These were then used to ascertain characteristics of Hong Kong Chinese
      patients' decision-making preferences for surgery. VALIDATION OF TOOL: Two sets
      of analyses tested the validity of picture cards in an Australian and Hong Kong
      Chinese population. First, the ratings of the two groups of participants using
      the picture cards for three scenarios (severe, moderate and mild medical
      conditions) were correlated with mean ratings of three decision-making subscales
      of a self-report questionnaire for the three scenarios. Second, a 3 (Scenario) x
      2 (Ethnic Group) mixed anova examined whether the picture cards are sensitive to
      differences relating to severity of medical conditions and ethnicity. SETTING AND
      PARTICIPANTS: A convenience sample of initially 35 Hong Kong and 24 Australian
      patients was used to validate the picture card tool. A convenience sample of a
      further 186 Hong Kong Chinese surgical inpatients used the tool. DESIGN:
      Participants selected the picture card that best represented their decision
      making preference. MAIN VARIABLES: Demographic factors, prior knowledge, nature
      of surgery and preference for participation in decision making. RESULTS:
      Significant correlations were made between the questionnaire and the picture card
      tool. Using the tool, a significant difference was found between males' and
      females' decision-making preference, yet, no significant difference was found
      with respect to type or previous surgical operation.

PMID- 16436159
TI  - A shared treatment decision-making approach between patients with chronic
      conditions and their clinicians: the case of diabetes.
AB  - In this paper, we discuss the Charles et al. approach to shared treatment
      decision-making (STDM) as applied to patients with chronic conditions and their
      clinicians. We perceive differences between the type of treatment decisions (e.g.
      end-of-life care, surgical treatment of cancer) that generated existing
      approaches of shared decision-making for acute care conditions (including the
      Charles et al. model) and the treatment decisions that patients with chronic
      conditions need to make and revisit on an ongoing basis. For instance, treatment
      decisions in the chronic care setting are more likely to require a more active
      patient role in carrying out the decision and to offer a longer window of
      opportunity to make decisions and to revisit and reverse them without important
      loss than acute care decisions. The latter may require minimal patient
      participation to realize, are often urgent, and may be irreversible. Given these
      differences, we explore the applicability of the Charles et al. model of STDM in
      the chronic care context, especially chronic care that relies heavily on patient
      self-management (e.g. diabetes). To apply the Charles et al. model in this
      clinical context, we suggest the need to emphasize the patient-clinician
      relationship as one of partners in making difficult treatment choices and to add
      a new component to the shared decision-making approach: the need for an ongoing
      partnership between the clinical team (not just the clinician) and the patient.
      In the last section of the paper, we explore potential healthcare system barriers
      to STDM in chronic care delivery. Throughout the discussion we identify areas for
      further research.

PMID- 16436160
TI  - What is a health expectation? Developing a pragmatic conceptual model from
      psychological theory.
AB  - INTRODUCTION: Examination of the existing literature in respect of health
      expectations revealed both ambiguity in relation to terminology, and relatively
      little work in respect of how abstract theories of expectancy in the
      psychological literature might be used in empirical research into the influence
      of expectations on attitudes and behaviours in the real world. This paper
      presents a conceptual model for the development of health expectations with
      specific reference to Alzheimer's disease. METHOD: Literature review, synthesis
      and conceptual model development, illustrated by the case of a person with newly
      diagnosed, early-stage Alzheimer's disease, and her caregiver. OUTCOME: Our model
      envisages the development of a health expectation as incorporating several
      longitudinal phases (precipitating phenomenon, prior understanding, cognitive
      processing, expectation formulation, outcome, post-outcome cognitive processing).
      CONCLUSION: Expectations are a highly important but still relatively poorly
      understood phenomenon in relation to the experience of health and health care. We
      suggest a pragmatic conceptual model designed to clarify the process of
      expectation development, in order to inform future research into the measurement
      of health expectations and to enhance our understanding of the influence of
      expectations on health behaviours and attitudes.

PMID- 16436161
TI  - Perceptions of communication between people with communication disability and
      general practice staff.
AB  - OBJECTIVE: To explore consultation between people with communication disability
      and General Practice (GP) staff from the perspectives of both patients and staff.
      BACKGROUND: Communication disability causes a particular problem in primary care.
      This issue has not yet been investigated from the perspective of both patients
      and GP staff. DESIGN: Eight focus groups were held - four with GP practices, two
      with people with intellectual disability and two with people who had had a
      stroke. Picture symbols and Talking Mats, a visual communication framework, were
      used to assist the participants with communication disability. Discussions were
      audio recorded and analysed thematically. PARTICIPANTS: Twenty GP staff, 12
      people with aphasia and six people with learning disability were interviewed.
      RESULTS: GP staff expressed frustration with not being understood and not
      understanding but there was a lack of awareness of the reasons behind these
      difficulties. They all said they mainly relied on carers. They recognized the
      significance of poor communication in terms of access to health services and
      agreed that the extent of the problem was greater than they had previously
      believed. People with communication disability described significant problems
      before, during and after the consultation. Although some acknowledged that they
      needed help from their carer, most objected to staff speaking to the carer and
      not to them. CONCLUSIONS: The main priorities for GP staff were the need for
      relevant training and simple resources. The main priorities for people with
      communication difficulty were continuity of staff, trust, better GP staff
      communication skills, and less reliance on carers.

PMID- 16436162
TI  - The introduction of integrated out-of-hours arrangements in England: a discrete
      choice experiment of public preferences for alternative models of care.
AB  - OBJECTIVE: To establish which generic attributes of general practice out-of-hours
      health services are important to the public. METHODS: A discrete choice
      experiment postal survey conducted in three English general practitioner (GP) co
      operatives. A total of 871 individuals aged 20-70 years registered with a GP.
      Outcomes were preferences for, and trade-offs between: time to making initial
      contact, time waiting for advice/treatment, informed of expected waiting time,
      type of contact, professional providing advice, chance contact relieves anxiety,
      and utility estimates for valuing current models of care. RESULTS: Response rate
      was 37%. Respondents valued out-of-hours contact for services for reducing
      anxiety but this was not the only attribute of importance. They had preferences
      for the way in which services were organized and valued information about
      expected waiting time, supporting findings from elsewhere. Participants were most
      willing to make trade-offs between waiting time and professional person. Of the
      predicted utility for three models of care utility was higher for fully
      integrated call management. CONCLUSIONS: Greater utility might be achieved if
      existing services are re-configured more in line with the government's fully
      integrated call management model. Because the attributes were described in
      generic terms, the findings can be applied more generally to the plethora of
      models that exist (and many that might exist in the future). The approach used is
      important for achieving greater public involvement in how health services
      develop. Few experiments have elicited public preferences for health services in
      the UK to date. This study showed valid preferences were expressed but there were
      problems obtaining representative views from the public.

PMID- 16436163
TI  - 'Taking off the suit': engaging the community in primary health care decision
      making.
AB  - OBJECTIVE: To explore the process of public involvement in planning primary
      health care. BACKGROUND: Recent policy in the UK promotes public involvement in
      planning health but there have been difficulties in engaging communities in the
      process. Surveys of health service organizations have found that there has been a
      failure to adapt to new approaches. It has become important to understand why
      this has occurred if policy initiatives to encourage involvement are to succeed.
      DESIGN: Qualitative study. Data collected through individual interviews and focus
      groups. SETTING: Two new primary healthcare developments in deprived areas in
      Bristol and Weston-Super-Mare. PARTICIPANTS: Thirty-six professionals and 23
      local residents in Bristol; six professionals and three local residents in Weston
      Super-Mare. RESULTS: Three themes were identified: process, partnership and
      power. The main findings were that exceptional people with a shared commitment to
      public involvement were necessary to motivate others and develop partnerships.
      Local people were drawn into the process and with increased confidence became
      powerful advocates for their community. Creative and varied methods to involve
      the public were important in achieving balance between professionals and lay
      people. However, conflicts over practical decisions arose from a lack of clarity
      over who had power to influence decisions. CONCLUSION: Most of the participants
      were enthusiastic about their experience of public involvement in planning
      primary health care. Features crucial to sustainable involvement included a
      commitment from leaders within statutory agencies, support over a long period to
      build the confidence of local people, willingness to use informal approaches that
      are in tune with local culture, and a recognition of the concerns of both service
      users and providers.

PMID- 16436164
TI  - Patients' perceptions of joint teleconsultations: a qualitative evaluation.
AB  - OBJECTIVE: To determine patient perceptions of joint teleconsultations (JTC),
      with particular reference to reasons underlying, and factors contributing to,
      patient satisfaction and dissatisfaction with this mode of health delivery.
      BACKGROUND: Telemedicine has been welcomed as one way of improving health-care
      delivery, by improving patient access to secondary care and specialist services
      hence widening patient choice, particularly for patients outside major
      conurbations. However, a recent systematic review found currently available data
      on patient satisfaction with telemedicine to be methodologically flawed.
      Qualitative evaluations offer the opportunity to elucidate the details of patient
      satisfaction with this mode of health-care delivery. DESIGN: Qualitative study
      using semi-structured interviews. SETTING AND PARTICIPANTS: Purposive sample of
      28 participants of a major randomized controlled trial (Virtual Outreach study)
      of JTC conducted in one urban and one rural area in Britain. INTERVENTION: Joint
      teleconferenced consultations with the patient, patient's general practitioner
      (GP), and a hospital specialist. The patient and GP were sited in the local
      practice, while the hospital specialist was in the hospital outpatient
      department, and the two parties were connected by an ISDN2 link and video
      conferencing software. MAIN OUTCOME MEASURES: Patient experiences of JTC, with
      particular reference to reasons underlying, and factors contributing to, overall
      satisfaction or dissatisfaction. RESULTS: Two major themes were identified:
      customer care and doctor-patient interaction. Patients appreciated the customer
      care aspects of JTC, particularly the enhanced convenience, reduced costs and
      improved punctuality associated with JTC. However, there were divergent views
      about the doctor-patient interactions with some patients expressing a sense of
      alienation arising from the use of technology, and problems with doctor-patient
      communication. CONCLUSIONS: These data add significantly to the existing
      literature on patient satisfaction with telemedicine, by elucidating the factors
      underlying overall satisfaction scores and hence have implications for future
      service delivery and implementation of telemedicine.

PMID- 16436165
TI  - Talking about tamoxifen.

PMID- 16436166
TI  - Involvement of the consumer voice.

PMID- 16436168
TI  - Cancer information seeking.

PMID- 16436170
TI  - Rights of and duties to non-consenting patients--informed refusal in the
      developing world.
AB  - The principle of informed refusal poses a specific problem when it is invoked by
      a pregnant woman who, in spite of having accepted her pregnancy, refuses the
      diagnostic and/or therapeutic measures that would ensure the well-being of her
      endangered fetus. Guidelines issued by professional bodies in the developed world
      are conflicting: either they allow autonomy and informed consent to be overruled
      to the benefit of the fetus, or they recommend the full respect of these
      principles. A number of medical ethicists advocate the overruling of alleged
      irrational or unreasonable refusal for the benefit of the fetus. The present
      essay supports the view of fetal rights to health and to life based on the
      principle that an 'accepted' fetus is a 'third person'. In developing countries,
      however, the implementation of the latter principle is likely to be in conflict
      with a 'communitarian' perception of the individual -- in this case, the pregnant
      woman. Within the scope of the limitations to the right to autonomy of J.S.
      Mill's 'harm principle', the South African Patients' Charter makes provision for
      informed refusal. The fact that, in practice, it is not implemented illustrates
      the well-known difficulty of applying Western bioethical principles in real life
      in the developing world.

PMID- 16436169
TI  - Mother-to-child transmission of HIV in Botswana: an ethical perspective on
      mandatory testing.
AB  - Mother-to-child transmission (MTCT) of HIV represents a particularly dramatic
      aspect of the HIV epidemic with an estimated 600,000 newborns infected yearly,
      90% of them living in sub-Saharan Africa. Since the beginning of the HIV
      epidemic, an estimated 5.1 million children worldwide have been infected with
      HIV. MTCT is responsible for 90% of these infections. Two-thirds of the MTCT are
      believed to occur during pregnancy and delivery, and about one-third through
      breastfeeding. As the number of women of child bearing age infected with HIV
      rises, so does the number of infected children. It is apparent that voluntary
      testing in Botswana has made some valuable inroads in decreasing perinatal HIV
      transmission, but the statistics showing the increased rate of HIV infection
      among women 15-24 years of age are not very promising. After reviewing all the
      pertinent scientific data it is clear that mandatory HIV testing of all pregnant
      women in conjunction with the implementation of a full package of interventions
      would save thousands of lives -- mothers, newborns and others who could be
      infected as a result of these women not being aware of their HIV status. If the
      protection and preservation of human life is a priority in Botswana, then it is
      time to allow for mandatory HIV testing of all pregnant women, before it is too
      late for those who are the most vulnerable. To do less would be medically
      inappropriate and ethically irresponsible.

PMID- 16436171
TI  - My job is to keep him alive, but what about his brother and sister? How Indian
      doctors experience ethical dilemmas in neonatal medicine.
AB  - BACKGROUND: Studies from Western countries show that doctors working in neonatal
      intensive care units (NICUs) find withdrawal of treatment to be their most
      difficult ethical dilemma. There is less knowledge of how this is experienced in
      other economic, cultural, religious and educational contexts. OBJECTIVES: To
      explore and describe how Indian doctors experience ethical dilemmas concerning
      the withdrawal of treatment among critically sick and/or premature neonates.
      METHOD: Qualitative data from interviews was analysed according to Giorgi's
      phenomenological approach. The subjects were 14 doctors with various levels of
      neonatal experience, recruited from two state-owned NICUs in India. MAIN OUTCOME
      MEASURES: description reflecting the nature of ethical dilemmas and how they are
      experienced. RESULTS: All doctors reported situations where the question of
      withdrawal of treatment was experienced as the worst part of their job. They felt
      that they lacked training in how to handle such dilemmas, and some had never
      talked about ethics before. They were especially concerned about non-medical
      considerations that do not feature in current treatment guidelines. In describing
      their personal experiences, the informants mentioned their sense of
      responsibility in situations where they were aware that their decisions would
      influence a family's economy and reputation, availability of food and education
      for siblings, other children's access to equipment in the unit, and the use of
      resources in an underprivileged population. Sometimes lack of resources, usually
      ventilators, forced them to make decisions about which babies should get the
      chance to live. Other reported dilemmas included difficulties co-operating with
      uneducated and poor parents. CONCLUSION: While Western doctors seem to focus on
      the rights and problems of the individual child, Indian doctors tend to refer to
      consequences for other children, for parents and society. There is a need for
      further research in this field, and for the development of guidelines on how to
      cope with differences in resources, and how to handle different patient groups'
      cultural and religious concerns.

PMID- 16436172
TI  - Informed consent and collaborative research: perspectives from the developing
      world.
AB  - INTRODUCTION: Informed consent has been recognized as an important component of
      research protocols and procedures of disclosure and consent in collaborative
      research have been criticized, as they may not be in keeping with cultural norms
      of developing countries. This study, which is part of a larger project funded by
      the United States National Bioethics Advisory Commission, explores the opinions
      of developing country researchers regarding informed consent in collaborative
      research. METHODS: A survey of developing country researchers, involved in human
      subject research, was conducted by distributing a questionnaire with 169
      questions, which included questions relating to informed consent. In addition,
      six focus group discussions, eight in-depth interviews and 78 responses to open
      ended questions in the questionnaire provided qualitative data. RESULTS: 203
      surveys were considered complete and were included in the analysis. Written
      consent was not used by nearly 40% of the researchers in their most recent
      studies. A large proportion of respondents recommended that human subject
      regulations should allow more flexibility in ways of documenting informed
      consent. 84% of researchers agreed that a mechanism to measure understanding
      should be incorporated in research studies as part of the process of informed
      consent. DISCUSSION: This paper is an empirical step in highlighting the ethical
      issues concerning disclosure. Health researchers in developing countries are well
      aware of the importance of consent in health research, and equally value the
      significance of educating human subjects regarding study protocols and associated
      risks and benefits. However, respondents emphasize the need for modifying ethical
      regulations in collaborative research.

PMID- 16436173
TI  - Informed consent in clinical research at a general hospital in Mexico: opinions
      of the investigators.
AB  - In Mexico informed consent is a legal requirement that ensures that patients who
      are invited to participate in clinical trials are provided with all the
      information needed to decide whether to participate, or not, in a research
      protocol. To improve our understanding of the problems physicians in developing
      countries encounter, when obtaining informed consent (IC), we examined their
      opinion on the importance of IC in clinical research, the quantity and quality of
      the information provided to the participant, and the conditions in which the IC
      is obtained. Investigators considered that IC was useful to the patients,
      providing information that helped the patient to make a decision about his/her
      participation. Nevertheless, they felt that for some aspects of the research,
      like drug development in general, the use of placebos, and the randomization
      process, many of the patients were not capable of fully understanding the
      information provided, referring to the complexity of the information and
      illiteracy as the main reasons. Many investigators were not acquainted with some
      of the guidelines established in the Mexican General Law of Health,(1) 36% of
      them admitting to not having completed their IC letters. Most investigators gave
      only minutes to the patient to make a decision and 20% of ICs were obtained while
      the patient was hospitalized. Except for one investigator, all of them considered
      that specific training in medical ethics would be useful for the daily clinical
      work.

PMID- 16436174
TI  - Paired comparison of bathwater versus oral delivery of 8-methoxypsoralen in
      psoralen plus ultraviolet: A therapy for chronic palmoplantar psoriasis.
AB  - BACKGROUND: Both bath psoralen plus ultraviolet A (PUVA) and oral PUVA with 8
      methoxypsoralen (8-MOP) have been successfully used for the treatment of
      recalcitrant palmoplantar psoriasis. This trial was designed to assess the
      efficacy and side effects of the different treatment modalities in a randomized
      half-side comparison. METHODS: Eight patients with moderate-to-severe psoriasis
      on soles (n = 6) and/or palms (n = 8) were randomly assigned to receive bath PUVA
      treatment on one side and oral PUVA on the other. Initial treatment dose was 50%
      of the minimal phototoxic dose evaluated for bath PUVA and oral PUVA. Treatment
      was given three times a week for 4 weeks. Before treatment and every week a
      severity index (SI) was assessed by summing the scores of erythema, infiltration,
      scaling and vesicles evaluated on a scale from 0 to 4. After 4 weeks of treatment
      the half-side trial was finished and the treatment was continued on both sides
      with the more effective treatment regimen. RESULTS: Both bath PUVA and oral PUVA
      achieved a reduction of the mean initial SI from 5.9 (95% confidence intervals
      (CI) 4.5-8.0) to 3.3 (1.8-6.0) (44% SI reduction, P < 0.005, Student's paired t
      test) and 6.0 (5.0-7.8) to 2.9 (1.8-4.0) (52% SI reduction; P < 0.005),
      respectively. The statistical comparison of the entire 4-week study period
      revealed a significant better effect in lesions treated with oral PUVA compared
      with bath PUVA (P = 0.033). However, at 4 weeks, there was no significant
      difference between the achieved SI reduction of oral PUVA and bath PUVA. Systemic
      side effects (nausea and/or dizziness) were only observed after oral PUVA.
      CONCLUSION: This study gives evidence that in the first 4 treatment weeks oral
      PUVA is slightly more effective than bath PUVA but the former has more systemic
      side effects.

PMID- 16436175
TI  - Narrow band Ultraviolet B 311 nm in the treatment of vitiligo: two right-left
      comparison studies.
AB  - AIM: Evaluation of narrow band ultraviolet B (NB UVB 311 nm) in the treatment of
      vitiligo by two independent studies. The first study compared NB UVB with a well
      established therapeutic modality, psoralen ultraviolet A (PUVA), and the second
      study was conducted to find out whether psoralen might add to its efficacy.
      METHODS: In the first study, 15 patients were exposed on the left half of their
      body to UVB 311 nm and then exposed on their right half to UVA after ingestion of
      psoralen. In the second study, 20 patients were exposed to UVB 311 nm on the left
      side of the body, followed by ingestion of psoralen and exposure to NB UVB 311 nm
      90 min later to the right side of the body. In both studies, while exposing one
      side, the other was protected by an UV-proof gown. Thus two right-left
      comparative studies were carried out simultaneously, namely: UVB 311 nm vs. PUVA
      and UVB 311 nm vs. PUVB 311 nm. RESULTS: In the first study, comparison of PUVA
      and NB UVB 311 nm showed no difference either in the degree of response or in the
      incidence of complications. In the second study, comparison of PUVB and UVB
      showed equal clinical improvement on both sides. The cumulative dose needed to
      achieve the same response on the PUVB side was lower than that on the UVB side,
      but the difference was not statistically significant. The incidence of phototoxic
      reactions was significantly higher on the PUVB treated body half. CONCLUSION: NB
      UVB 311 nm has similar repigmentary effects as PUVA. The addition of psoralen
      does not increase its efficacy.

PMID- 16436176
TI  - The effect of ultra violet B (TL-01) phototherapy on epidermal expression of p53
      protein in psoriatic plaques.
AB  - BACKGROUND: Psoriasis is a genetically determined inflammatory skin disease. It
      is now recognized that narrow band TL-01 phototherapy is an effective treatment
      for psoriasis. However, ultraviolet (UV) exposure induces p53 mutations in
      keratinocytes and repeated exposure of skin to UV radiation results in clonal
      expansion of these initiated p53-mutant cells within the epidermis. AIM: The
      present study aims to examine epidermal p53 expression in the skin of psoriatic
      patients at different time points following TL-01 phototherapy. METHODS: Skin
      samples from patients suffering from plaque-type psoriasis, collected before,
      during and at the final stages of TL-01 phototherapy were examined for p53
      expression by immunohistochemistry. RESULTS/CONCLUSION: Our results showed an
      increase in p53 expressing keratinocytes following TL-01 phototherapy. Some of
      these cells were arranged spatially, as conical clones arising from putative stem
      cell compartments, suggesting that the chronic TL-01 treatment might have
      triggered cell growth and clonal expansion, an important step in initiating skin
      carcinogenesis.

PMID- 16436177
TI  - Photoprotection in teenagers.
AB  - BACKGROUND: It is very common to apply a 'template photoprotection' without
      taking into consideration the background of a specific population. In Lebanon, so
      far, no preliminary survey has been conducted before launching an educational
      photoprotection campaign, revealing the need of the people according to their
      background. MATERIALS AND METHODS: In April 2004, a specific questionnaire was
      administered to 940 adolescents, aged from 14 to 18 years. The questionnaire
      comprised 18 multiple-choice questions that established the approximate phototype
      of teenagers, awareness of ultraviolet (UV) hazard, presence of sufficient
      information regarding the risk of sun exposure (school, doctor, media) and the
      use of measures of photoprotection (clothes, sunscreens). RESULTS: The incidence
      of sunburn in teenagers was high (85.42%) despite their awareness of the risks of
      unprotected sun exposure. The information regarding sun damage seems to be
      insufficiently delivered at school and by doctors. The main source of information
      was television. It was obvious that our adolescents underestimated the value of
      clothing to protect themselves. The use of clothing comes at the second place
      after sunscreens. However, the application of sunscreen seems to be inadequate.
      CONCLUSIONS: While solar protection has become part of routine beach behavior for
      adolescents, there is room for improvement with better application of sunscreen
      and more use of clothing, especially wearing hats, and seeking shade. However, it
      is difficult to appreciate the impact of publicity campaigns on the risks of sun
      exposure in reducing the incidence of melanoma.

PMID- 16436178
TI  - Protection of skin biological targets by different types of sunscreens.
AB  - In vitro and in vivo studies provide a body of evidence that adequate protection
      of the skin against ultraviolet (UV)-induced damage requires photostable broad
      spectrum sunscreens with a proper level of UVA protection. UVA alone and UV solar
      simulated radiation (SSR) induce DNA lesions in keratinocytes and melanocytes as
      reflected by the comet assay and p53 accumulation. UVA and SSR impair the immune
      system as shown by significant alteration of Langerhans cells and inhibition of
      contact hypersensitivity response to chemical allergens and delayed-type
      hypersensitivity response to recall antigens. Any of these detrimental effects is
      more efficiently prevented by sunscreens with a higher level of protection in the
      UVA range. The involvement of UVA (fibroblast alteration, increased
      metalloproteinase expression) and the pivotal need for well-balanced UVA/UVB
      sunscreens were further demonstrated using reconstructed three-dimensional skin
      models.

PMID- 16436179
TI  - Effects of low-power laser radiation on mice immunity.
AB  - BACKGROUND/PURPOSE: Because of large interest in biological effects of laser
      radiation used in laser therapy, the effect of extremely low-level red laser
      light intensity on the immune cell activity has been studied in the animal model
      with well-characterized macrophage and T cell populations as responder cells
      producing cytokines, protective proteins, active oxygen, and nitric compounds. To
      study of the possible side effects of laser immunotherapy we monitored the
      productions of cytokines, nitric oxide (NO), and heat shock protein 70 (Hsp70) in
      mice subjected to a periodic laser exposure for 1 month. METHODS: Helium-neon
      laser radiation with the power of 0.2 mW/cm2 and wavelength of 632.8 nm was
      applied on two different mouse skin surfaces, i.e. a thymus projection area or a
      hind limb. Healthy NMRI male mice were irradiated repeatedly with laser light for
      1 min with 48-h intervals for 30 days. The animals were divided into three groups
      of 25 mice. The first and the second groups were exposed to laser light, on the
      thymus and hind limb area, respectively. The third, sham-irradiated group served
      as a control. Early and prolonged effects of laser radiation on the levels of NO
      (by Griess assay), Hsp70 (by Western blot assay), tumor necrosis factors (TNF
      alpha and TNF-beta) (by cytotoxic assay using L929 cells as targets), and
      interleukin-2 (IL-2) (by ELISA assay) were determined. RESULTS: The dynamics of
      immune responses to low-power laser light intensity was shown to be dependent on
      two factors, i.e. the cumulative dose and the localization of the irradiated
      surface. Besides, various populations of cells demonstrated different sensitivity
      to laser radiation, with T cells being more responsive among examined populations
      of the cells. Low intensity laser light induced an immune cell activity when the
      exposure duration did not exceed 10 days, while a more prolonged period of
      treatment generated more severe changes in the immune system, up to
      immunosuppression. The treatment of the thymus zone resulted in more pronounced
      changes in the cytokine production as well as in NO and Hsp70 synthesis.
      CONCLUSION: Low-power laser irradiation showed more effective immunomodulatory
      effects when applied on the thymus projection area. The rise in IL-2 and Hsp70
      production related to a short-term effect of laser application may be reversed
      after repeating laser treatment. We suggest that for the support of immune system
      stability, the prolonged laser therapy should be accompanied by supplementary
      methods.

PMID- 16436180
TI  - Skin surface topography grading is a valid measure of skin photoaging.
AB  - BACKGROUND: The technique of grading the surface topography of sun-exposed skin
      using silicone impressions of the skin surface is a simple, non-invasive method
      for measuring skin damage because of sun exposure, but it has never been
      validated in a community setting. OBJECTIVE: To investigate the repeatability and
      validity of using standardly-graded skin impressions as a means of assessing skin
      photoaging. PATIENTS/METHODS: A random sample of 195 adults aged 18-79 years and
      living in Nambour, Australia (latitude, 26 degrees South) had a silicone
      impression taken of the back of the left hand and a 2 mm punch biopsy of the skin
      at the same site. Silicone impressions were graded twice independently and
      histological photoaging was determined by two pathologists. RESULTS: Grading of
      silicone impressions of skin surface topography was highly repeatable (weighted
      kappa > 0.8). Compared with those with low skin impression grades (least
      degeneration), people with high grades were three times more likely to show a
      high degree of dermal elastosis on skin histology (odds ratio 3.1, 95% confidence
      interval 1.6, 5.7) after adjusting for age, sex, skin colour, tanning ability,
      occupational exposure, smoking and height-adjusted weight. Other photoaging
      changes in the stratum corneum and dermis were also strongly correlated with high
      grades of damage on skin impressions. CONCLUSION: Grading silicone impressions of
      skin surface topography is a highly reliable and a valid measure of photoaging
      and enables prediction of dermal elastosis in a population setting.

PMID- 16436181
TI  - Spectroscopic assessment of dermal melanin using blue vitiligo as an in vivo
      model.
AB  - BACKGROUND: Spectroscopic methods have been used to analyze in vivo melanin in
      the past but the specific effect of melanin depth on autofluorescence and
      reflectance spectroscopy has not been determined. In patients with blue vitiligo,
      three distinctive clinicopathologic patterns are present: (1) normal skin with
      normal epidermal melanin pigmentation (2), skin of blue vitiligo with dermal
      melanin pigmentation, and (3) tissue of regular vitiligo with no melanin
      pigmentation. Blue vitiligo may thus serve as an in vivo model to assess dermal
      pigment using spectroscopic techniques. OBJECTIVES: To evaluate the reflectance
      and autofluorescence spectra of a patient with blue vitiligo in order to assess
      the effect of melanin pigmentation and its localization on the optical properties
      of the skin. METHODS: The blue-gray, normal and depigmented lesions of a patient
      with blue vitiligo were analyzed using reflectance and fluorescent spectroscopy.
      The condition was likely induced by a phototoxic reaction in a patient with pre
      existing vitiligo. These data were then correlated to the histologic and electron
      microscopic findings present in the various types of lesions. RESULTS:
      Reflectance spectroscopy detected little difference in spectral shape between
      skin sites affected by blue vitiligo vs. vitiligo. Autofluorescence spectroscopy
      detected an apparent difference between the two types of lesions, with the blue
      gray lesions (blue vitiligo) showing lower fluorescence intensity and spectral
      maximum position red-shifted compared with regular vitiligo, whereas regular
      vitiligo showed more intense hemoglobin absorption than the blue vitiligo.
      CONCLUSIONS: Dermal melanin present in blue vitiligo can be well characterized by
      autofluorescence spectroscopy, while little difference in reflectance spectral
      shape exists between vitiligo and blue vitiligo. Thus, autofluorescence
      spectroscopy may better identify deeper structures in skin tissue, such as
      melanin, than reflectance spectroscopy.

PMID- 16436182
TI  - Action spectrum for healing of psoriasis.

PMID- 16436183
TI  - Fine mapping of a sedative-hypnotic drug withdrawal locus on mouse chromosome 11.
AB  - We have established that there is a considerable amount of common genetic
      influence on physiological dependence and associated withdrawal from sedative
      hypnotic drugs including alcohol, benzodiazepines, barbiturates and inhalants. We
      previously mapped two loci responsible for 12 and 9% of the genetic variance in
      acute alcohol and pentobarbital withdrawal convulsion liability in mice,
      respectively, to an approximately 28-cM interval of proximal chromosome 11. Here,
      we narrow the position of these two loci to a 3-cM interval (8.8 Mb, containing
      34 known and predicted genes) using haplotype analysis. These include genes
      encoding four subunits of the GABA(A) receptor, which is implicated as a pivotal
      component in sedative-hypnotic dependence and withdrawal. We report that the
      DBA/2J mouse strain, which exhibits severe withdrawal from sedative-hypnotic
      drugs, encodes a unique GABA(A) receptor gamma2 subunit variant compared with
      other standard inbred strains including the genetically similar DBA/1J strain. We
      also demonstrate that withdrawal from zolpidem, a benzodiazepine receptor agonist
      selective for alpha1 subunit containing GABA(A) receptors, is influenced by a
      chromosome 11 locus, suggesting that the same locus (gene) influences risk of
      alcohol, benzodiazepine and barbiturate withdrawal. Our results, together with
      recent knockout studies, point to the GABA(A) receptor gamma2 subunit gene
      (Gabrg2) as a promising candidate gene to underlie phenotypic differences in
      sedative-hypnotic physiological dependence and associated withdrawal episodes.

PMID- 16436184
TI  - Cloninger's temperament dimensions and epidermal growth factor A61G polymorphism
      in Finnish adults.
AB  - This study examines a link between human temperament and epidermal growth factor
      (EGF). There is evidence that dopaminergic neurotransmission in the central
      nervous system has a role in temperament, especially in novelty seeking.
      Functional polymorphism in EGF gene has an impact on EGF production, and EGF, in
      turn, appears to affect the development of midbrain dopaminergic neurons.
      Epidermal growth factor gene A61G polymorphisms were studied in a randomly
      selected sample of 292 Finnish adults. Their temperaments were assessed twice
      (with a 4-year test-retest interval) with Cloninger's Temperament and Character
      Inventory consisting of four dimensions, i.e. novelty seeking (NS), harm
      avoidance (HA), reward dependence (RD) and persistence (P). The findings on men
      showed a significant association between a presence of the G/G polymorphism and
      scoring in the highest tertile on NS in both test and retest. The same was true
      with men who scored high on RD, especially on sensitivity, in both tests. Among
      women, G/G polymorphism was associated with a stable high level of P.
      Importantly, temperament dimensions, as assessed with one test only, did not
      provide replicable associations with EGF polymorphism across the two
      measurements. Our results demonstrate the importance of reliable phenotype
      assessment and lend support to the hypothesis that dopaminergic activity is one
      factor underlying stable temperament.

PMID- 16436185
TI  - A genetic screen for behavioral mutations that perturb dopaminergic homeostasis
      in mice.
AB  - Disruption of dopaminergic (DA) systems is thought to play a central role in the
      addictive process and in the pathophysiology of schizophrenia. Although
      inheritance plays an important role in the predisposition to these disorders, the
      genetic basis of this is not well understood. To provide additional insight, we
      have performed a modifier screen in mice designed to identify mutations that
      perturb DA homeostasis. With a genetic background sensitized by a mutation in the
      dopamine transporter (DAT), we used random chemical mutagenesis and screened for
      mutant mice with locomotor abnormalities. Four mutant lines were identified with
      quantitatively elevated levels of locomotor activity. Mapping of mutations in
      these lines identified two loci that alter activity only when dopamine levels are
      elevated by a DAT mutation and thus would only have been uncovered by this type
      of approach. One of these quantitative trait loci behaves as an enhancer of DA
      neurotransmission, whereas the other may act as a suppressor. In addition, we
      also identified three loci which are not dependent on the sensitized background
      but which also contribute to the overall locomotor phenotype.

PMID- 16436186
TI  - Paradoxical effects of learning the Morris water maze on adult hippocampal
      neurogenesis in mice may be explained by a combination of stress and physical
      activity.
AB  - Studies in rats that assessed the relation of hippocampus-dependent learning and
      adult hippocampal neurogenesis suggested a direct regulatory effect of learning
      on neurogenesis, whereas a similar study in mice had not found such causal link.
      We here report a substantial decrease of BrdU-positive cells and other measures
      of adult hippocampal neurogenesis in mice trained in the hidden (HID) or cued
      version (VIS) of the Morris water maze as compared to untrained animals (CTR).
      Particularly, cells on advanced stages of neuronal development contributed to
      this decrease, whereas earlier progenitors (type 2 cells) were not diminished in
      HID, but were diminished in VIS as compared to CTR. The differential regulation
      of type 2 cells in HID and VIS may have been caused by a different degree of
      physical activity, given that a time-yoked control group did not differ from HID,
      and type 2 cells reportedly constitute the proliferative dentate gyrus population
      that primarily responds to physical activity. The decrease of hippocampal
      neurogenesis by water maze training was reversible by pre-exposing animals to the
      water maze prior to training, suggesting that stress associated with training may
      have caused the acute downregulation of adult neurogenesis. We propose that in
      mice the Morris water maze does not provide a pure enough learning stimulus to
      study the presumed effects of 'learning' on adult neurogenesis. In addition,
      however, our data show that physical activity that is intricately linked to many
      cognitive tasks in rodents might play an important role in explaining effects of
      learning on cellular hippocampal plasticity.

PMID- 16436187
TI  - Structural variation of the monoamine oxidase A gene promoter repeat polymorphism
      in nonhuman primates.
AB  - By conferring allele-specific transcriptional activity on the monoamine oxidase A
      (MAOA) gene in humans, length variation of a repetitive sequence [(variable
      number of tandem repeat (VNTR)] in the MAOA promoter influences a constellation
      of personality traits related to aggressive and antisocial behavior and increases
      the risk of neurodevelopmental and psychiatric disorders. Here, we have analyzed
      the presence and variability of this MAOA promoter repeat in several species of
      nonhuman primates. Sequence analysis of MAOA's transcriptional control region
      revealed the presence of the VNTR in chimpanzee (Pan troglodytes), bonobo (Pan
      paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), rhesus macaque
      (Macaca mulatta) and Gelada baboon (Theropithecus gelada). The majority of P.
      troglodytes and P. paniscus showed a single repeat with a sequence identical to
      the VNTR sequence in humans. In contrast, analyses of the remaining species
      revealed shorter sequences similar to the first 18 bp of human VNTR. Compared
      with other nonhuman primates, the VNTR sequence of M. mulatta showed the highest
      length variability with allele frequencies of 35, 25 and 40% for the five, six
      and seven repeat variants, respectively. The extent of variability of the MAOA
      promoter repeat in both rhesus monkeys and humans supports the notion that there
      may be a relationship between functional MAOA expression and aggression-related
      traits in humans and rhesus macaque populations.

PMID- 16436188
TI  - Neural cell adhesion molecule (NCAM-/-) null mice show impaired sensitization of
      the startle response.
AB  - The neural cell adhesion molecule (NCAM) plays important roles in development of
      the nervous system and in synaptic plasticity and memory formation in the adult.
      The present study sought to further investigate the role of NCAM in learning by
      testing habituation and footshock sensitization learning of the startle response
      (SR) in NCAM null mutant (NCAM-/-) and wildtype littermate (NCAM+/+) mice.
      Whereas habituation is a form of non-associative learning, footshock
      sensitization is induced by rapid contextual fear conditioning. Habituation was
      tested by repetitive presentation of acoustic and tactile startle stimuli.
      Although NCAM-/- mice showed differences in sensitivity in both stimulus
      modalities, habituation learning was intact in NCAM-/- mice, suggesting that NCAM
      does not play a role in the mechanisms underlying synaptic plasticity in the
      startle pathway. Footshock sensitization was elicited by presentation of electric
      footshocks between two series of acoustic stimuli. In contrast to habituation,
      footshock sensitization learning was attenuated in NCAM-/- mice: the acoustic SR
      increase after the footshocks was lower in the mutant than in wildtype mice,
      indicating that NCAM plays an important role in the relevant brain areas, such as
      amygdala and/or the hippocampus.

PMID- 16436189
TI  - Selected line difference in sensitivity to a GABAergic neurosteroid during
      ethanol withdrawal.
AB  - The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of gamma
      aminobutyric acid(A) (GABA(A)) receptors. Earlier work indicates that sensitivity
      to the anticonvulsant effect of ALLO was enhanced during ethanol (EtOH)
      withdrawal in rats and in C57BL/6 mice, an inbred strain with mild EtOH
      withdrawal. In contrast, ALLO sensitivity was reduced during EtOH withdrawal in
      DBA/2 mice, an inbred strain with severe EtOH withdrawal. Thus, the present
      studies examined ALLO sensitivity during EtOH withdrawal in another animal model
      of EtOH withdrawal severity, the Withdrawal Seizure-Prone (WSP) and Withdrawal
      Seizure-Resistant (WSR) selected lines. Male mice were exposed to EtOH vapor or
      air for 72 h. During peak withdrawal, animals were injected with ALLO [0, 3.2, 5,
      10 or 17 mg/kg, intraperitoneally (i.p.)] and tested for their sensitivity to the
      anticonvulsant effect. In separate studies, potentiation of GABA-stimulated
      chloride uptake by ALLO (10 nm to 10 microm) was assessed in microsacs prepared
      from mouse brain mice during peak withdrawal. Notably, WSP mice were cross
      tolerant to the anticonvulsant effect of ALLO during EtOH withdrawal (i.e.
      significant decrease in the efficacy of ALLO) when compared with values in air
      exposed mice. In contrast, sensitivity to the anticonvulsant effect of ALLO was
      unchanged during EtOH withdrawal in the WSR line. Functional sensitivity of
      GABA(A) receptors to ALLO was significantly decreased during EtOH withdrawal in
      WSP mice in a manner consistent with the change in behavioral sensitivity to
      ALLO. These findings suggest that mice selectively bred for differences in EtOH
      withdrawal severity are differentially sensitive to ALLO during EtOH withdrawal.

PMID- 16436190
TI  - Environmental bias? Effects of housing conditions, laboratory environment and
      experimenter on behavioral tests.
AB  - Behavioral testing does not always yield similar results when replicated in
      different laboratories, and it usually remains unclear whether the variability in
      results is caused by different laboratory environments or different experimenters
      conducting the tests. In our study, we applied a systematic variation of housing
      conditions, laboratories and experimenters in order to test the influence of
      these variables on the outcome of behavioral tests. We wanted to know whether
      known effects of different housing conditions on behavior can be demonstrated
      regardless of the respective laboratory and experimenters. In this study, we
      compared the behavior of mice kept under enriched housing conditions with mice
      kept in unstructured cages regarding their exploratory, locomotor and anxiety
      related behavior in the barrier test, in the open-field test and in the elevated
      plus-maze test. Experiments were conducted by six different persons in two
      different laboratories. In spite of an extensive protocol standardizing
      laboratory environment, animal maintenance and testing procedures, significant
      differences in absolute values between different laboratories as well as between
      different experimenters were noticed in the barrier test and in the elevated plus
      maze test but not in the open-field test. However, with regard to the differences
      between enriched and unstructured housing conditions, overall consistent results
      were achieved by different experimenters in both laboratories. We conclude that
      the reliability of behavioral phenotyping is not challenged seriously by
      experimenter and laboratory environment as long as appropriate standardizations
      are met and suitable controls are involved.

PMID- 16436191
TI  - Synaptic hyperexcitability of deep layer neocortical cells in a genetic model of
      absence seizures.
AB  - We used sharp-electrode, intracellular recordings in an in vitro brain slice
      preparation to study the excitability of neocortical neurons located in the deep
      layers (>900 microm from the pia) of epileptic (180-210-days old) Wistar Albino
      Glaxo/Rijswijk (WAG/Rij) and age-matched, non-epileptic control (NEC) rats.
      Wistar Albino Glaxo/Rijswijk rats represent a genetic model of absence seizures
      associated with generalized spike and wave (SW) discharges in vivo. When filled
      with neurobiotin, these neurons had a typical pyramidal shape with extensive
      apical and basal dendritic trees; moreover, WAG/Rij and NEC cells had similar
      fundamental electrophysiological and repetitive firing properties. Sequences of
      excitatory postsynaptic potentials (EPSPs) and hyperpolarizing inhibitory
      postsynaptic potentials (IPSPs) were induced in both the strains by electrical
      stimuli delivered to the underlying white matter or within the neocortex;
      however, in 24 of 55 regularly firing WAG/Rij cells but only in 2 of 25 NEC
      neurons, we identified a late EPSP that (1) led to action potential discharge and
      (2) was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2
      carboxypiperazine-4-yl)-propyl-1-phosphonate (20 microM; n = 8/8 WAG/Rij cells).
      Finally, we found that the fast and slow components of the stimulus-induced IPSPs
      recorded during the application of glutamatergic receptor antagonists had similar
      reversal potentials in the two strains, while the peak conductance of the fast
      IPSP was significantly reduced in WAG/Rij cells. These findings document an
      increase in synaptic excitability that is mediated by NMDA receptors, in
      epileptic WAG/Rij rat neurons located in neocortical deep layers. We propose that
      this mechanism may be instrumental for initiating and maintaining generalized SW
      discharges in vivo.

PMID- 16436192
TI  - Molecular genetics of bipolar disorder.
AB  - Bipolar disorder (BPD) is an often devastating illness characterized by extreme
      mood dysregulation. Although family, twin and adoption studies consistently
      indicate a strong genetic component, specific genes that contribute to the
      illness remain unclear. This study gives an overview of linkage studies of BPD,
      concluding that the regions with the best evidence for linkage include areas on
      chromosomes 2p, 4p, 4q, 6q, 8q, 11p, 12q, 13q, 16p, 16q, 18p, 18q, 21q, 22q and
      Xq. Association studies are summarized, which support a possible role for
      numerous candidate genes in BPD including COMT, DAT, HTR4, DRD4, DRD2, HTR2A, 5
      HTT, the G72/G30 complex, DISC1, P2RX7, MAOA and BDNF. Animal models related to
      bipolar illness are also reviewed, with special attention paid to those with
      clear genetic implications. We conclude with suggestions for strategies that may
      help clarify the genetic bases of this complex illness.

PMID- 16436193
TI  - Tight regulation of transgene expression by tetracycline-dependent activator and
      repressor in brain.
AB  - Methods to temporally and spatially regulate gene mutations will provide a
      powerful strategy to investigate gene function in the brain. To develop these
      methods, we have established a tightly regulated system for transgene expression
      in the forebrain using both a tetracycline (Tc)-dependent transcription activator
      (rtTA) and a repressor (TetR-Kruppel-associated box). In this system, the
      repressor binds to the Tc-responsive element (TRE) in the absence of doxycycline
      (Dox), leading to the repression of leaky activation of TRE-mediated
      transcription caused by weak binding of rtTA to TRE. Upon Dox administration,
      only the activator binds to TRE and activates transcription. We tested this
      system in cultured cells by bicistronically expressing both the regulators using
      an internal ribosome entry site (IRES). In COS-1, HeLa and SHSY5Y cells, leaky
      transcription activation led by rtTA in the absence of Dox was repressed without
      decreasing the level of activated transcription in the presence of Dox. Using
      this system, transgenic mice were produced that express both the regulators using
      IRES in the forebrain under the control of the alphaCaMKII promoter and were bred
      with transgenic mice carrying the TRE-dependent reporter transgene. In reverse
      transcription-polymerase chain reaction and in situ hybridization analyses of the
      forebrain in adult double transgenic mice, the treatment of Dox induces reporter
      mRNA expression, which was not detected before the treatment and after the
      withdraw of Dox following the treatment. These results indicate that this system
      allows the tight regulation of transgene expression in a Dox-dependent fashion in
      the forebrain and will be useful in investigating gene function in the brain.

PMID- 16436194
TI  - The interaction between TPH2 promoter haplotypes and clinical-demographic risk
      factors in suicide victims with major psychoses.
AB  - Tryptophan hydroxylase isoform 2 (TPH2) is a rate-limiting enzyme in the
      biosynthesis of serotonin (5-HT) and is predominantly localized in the brain.
      Previous studies have suggested that there is an association between serotonergic
      dysfunction in the brain and suicidality. This study was designed to examine
      whether the -473T > A and -8396G > C polymorphisms of the TPH2 gene may be
      associated with completed suicide in subjects with major psychoses from the
      Stanley Foundation Brain Bank sample. TPH2 genotypes were determined in 69
      subjects with a diagnosis of schizophrenia or bipolar disorder, among which 22
      died by suicide. Genomic DNA was amplified by polymerase chain reaction and typed
      by automated methods. Both markers were found to be in Hardy-Weinberg equilibrium
      and in strong linkage disequilibrium. No association with history of suicide was
      found for either polymorphism. Haplotype analysis with EHAP showed no association
      between completed suicide and haplotype distribution (chi2 = 1.877; 3 df; P =
      0.598). Nor was there any association between suicide and these genetic markers
      even when clinical-demographic factors were considered as covariates in the
      haplotype analysis. These findings suggest that these 5' marker haplotypes in the
      TPH2 gene do not influence suicidal behaviour.

PMID- 16436197
TI  - Abstracts of the 107th Meeting of the British Neuropathological Society. London,
      United Kingdom. January 11-13, 2006.

PMID- 16436199
TI  - Detection and quantification of lupus anticoagulants in plasma from heparin
      treated patients, using addition of polybrene.
AB  - BACKGROUND: Lupus anticoagulants prolong clotting times in phospholipid-dependent
      coagulation tests. Lupus Ratio assays are integrated tests for lupus
      anticoagulants that may be based on APTT, RVVT or dPT clotting times. If a
      patient is being treated with unfractionated heparin, however, the heparin
      prolong clotting times and the diagnosis of lupus anticoagulant is invalidated.
      Commercial assays may have heparin neutralising agents added to their reagents.
      However, the type and efficacy of the heparin neutralisation is often not
      documented. We wanted to test the influence and efficacy of heparin neutralisers
      in the Lupus Ratio assay. METHODS: Several heparin neutralisers were tested, and
      polybrene was chosen for further testing. Unfractionated heparin and/or polybrene
      were added to normal plasma and to plasma from patients with or without lupus
      anticoagulant and clotting times compared before and after the additions. Lupus
      anticoagulant-positive patients were given 5000 IU i.v. of unfractionated heparin
      and plasma was collected just before and five minutes after the injection. Lupus
      Ratios were calculated after polybrene was added to the postinjection samples.
      RESULTS: The Lupus Ratio became slightly lower when polybrene was added to plasma
      without heparin. Plasma heparinised in vitro and plasma from patients that had
      received heparin, both had Lupus Ratios nearly identical to the Lupus Ratios
      calculated before any additions. CONCLUSION: By addition of polybrene to a final
      concentration of 7.9 microg/ml in test plasma, Lupus Ratio may be determined in
      lupus anticoagulant-negative as well as positive plasmas irrespective of the
      presence of heparin 0.0-1.3 U/ml.

PMID- 16436200
TI  - The description of cough sounds by healthcare professionals.
AB  - BACKGROUND: Little is known of the language healthcare professionals use to
      describe cough sounds. We aimed to examine how they describe cough sounds and to
      assess whether these descriptions suggested they appreciate the basic sound
      qualities (as assessed by acoustic analysis) and the underlying diagnosis of the
      patient coughing. METHODS: 53 health professionals from two large respiratory
      tertiary referral centres were recruited; 22 doctors and 31 staff from
      professions allied to medicine. Participants listened to 9 sequences of
      spontaneous cough sounds from common respiratory diseases. For each cough they
      selected patient gender, the most appropriate descriptors and a diagnosis.
      Cluster analysis was performed to assess which cough sounds attracted similar
      descriptions. RESULTS: Gender was correctly identified in 93% of cases. The
      presence or absence of mucus was correct in 76.1% and wheeze in 39.3% of cases.
      However, identifying clinical diagnosis from cough was poor at 34.0%. Cluster
      analysis showed coughs with the same acoustics properties rather than the same
      diagnoses attracted the same descriptions. CONCLUSION: These results suggest that
      healthcare professionals can recognise some of the qualities of cough sounds but
      are poor at making diagnoses from them. It remains to be seen whether in the
      future cough sound acoustics will provide useful clinical information and whether
      their study will lead to the development of useful new outcome measures in cough
      monitoring.

PMID- 16436202
TI  - Patterns of active and passive smoking, and associated factors, in the South-east
      Anatolian Project (SEAP) region in Turkey.
AB  - BACKGROUND: Smoking is an important health threat in Turkey. This study aimed to
      determine the frequency of and main factors associated with smoking in persons of
      15 years and over, and the frequency of passive smoking in homes in the South
      east Anatolian Project (SEAP) Region in Turkey. METHODS: A cross sectional design
      was employed. The sample was chosen by the State Institute of Statistics using a
      stratified cluster probability sampling method. 1126 houses representing the SEAP
      Region were visited. Questionnaires about tobacco smoking and related factors
      were applied to 2166 women and 1906 men (of 15 years old and above) in their
      homes. Face-to-face interview methods were employed. Participants were classified
      as current, ex, and non-smokers. The presence of a regular daily smoker in a
      house was used as an indication of passive smoking. The chi-square and logistic
      regression analysis methods were used for the statistical analysis. RESULTS: The
      prevalence of smoking, in those of 15 years and over, was 11.8% in women and
      49.7% in men. The prevalence of current smokers was higher in urban (34.5%) than
      in rural (22.8%) regions. The mean of total cigarette consumption was 6.5
      packs/year in women and 17.9 packs/year in men. There was at least one current
      smoker in 70.1% of the houses. CONCLUSION: Smoking is a serious problem in the
      South-eastern Anatolian Region. Male gender, middle age, a high level of
      education and urban residency were most strongly associated with smoking.

PMID- 16436203
TI  - Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and
      filter paper blood.
AB  - BACKGROUND: The reproducibilty of dengue IgM and IgG ELISA was studied in serum
      and filter paper blood spots from Vietnamese febrile patients. METHODS: 781 pairs
      of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161
      corresponding pairs of filter paper blood spots were tested with ELISA for dengue
      IgG and IgM. 74 serum pairs were tested again in another laboratory with similar
      methods, after a mean of 252 days. RESULTS: Cases were classified as no dengue
      (10 %), past dengue (55%) acute primary (7%) or secondary (28%) dengue.
      Significant differences between the two laboratories' results were found leading
      to different diagnostic classification (kappa 0.46, p < 0.001). Filter paper
      results correlated poorly to serum values, being more variable and lower with a
      mean (95% CI) difference of 0.82 (0.36 to 1.28) for IgMt3, 0.94 (0.51 to 1.37)
      for IgGt0 and 0.26 (-0.20 to 0.71) for IgGt3. This also led to differences in
      diagnostic classification (kappa value 0.44, p < 0.001) The duration of storage
      of frozen serum and dried filter papers, sealed in nylon bags in an air
      conditioned room, had no significant effect on the ELISA results. CONCLUSION:
      Dengue virus IgG antibodies in serum and filter papers was not affected by
      duration of storage, but was subject to inter-laboratory variability. Dengue
      virus IgM antibodies measured in serum reconstituted from blood spots on filter
      papers were lower than in serum, in particular in the acute phase of disease.
      Therefore this method limits its value for diagnostic confirmation of individual
      patients with dengue virus infections. However the detection of dengue virus IgG
      antibodies eluted from filter paper can be used for sero-prevalence cross
      sectional studies.

PMID- 16436204
TI  - GPNN: power studies and applications of a neural network method for detecting
      gene-gene interactions in studies of human disease.
AB  - BACKGROUND: The identification and characterization of genes that influence the
      risk of common, complex multifactorial disease primarily through interactions
      with other genes and environmental factors remains a statistical and
      computational challenge in genetic epidemiology. We have previously introduced a
      genetic programming optimized neural network (GPNN) as a method for optimizing
      the architecture of a neural network to improve the identification of gene
      combinations associated with disease risk. The goal of this study was to evaluate
      the power of GPNN for identifying high-order gene-gene interactions. We were also
      interested in applying GPNN to a real data analysis in Parkinson's disease.
      RESULTS: We show that GPNN has high power to detect even relatively small genetic
      effects (2-3% heritability) in simulated data models involving two and three
      locus interactions. The limits of detection were reached under conditions with
      very small heritability (<1%) or when interactions involved more than three loci.
      We tested GPNN on a real dataset comprised of Parkinson's disease cases and
      controls and found a two locus interaction between the DLST gene and sex.
      CONCLUSION: These results indicate that GPNN may be a useful pattern recognition
      approach for detecting gene-gene and gene-environment interactions.

PMID- 16436205
TI  - Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory
      phenotype and provide a cellular system for studies of glial inflammation.
AB  - Detailed study of glial inflammation has been hindered by lack of cell culture
      systems that spontaneously demonstrate the "neuroinflammatory phenotype". Mice
      expressing a glycine --> alanine substitution in cytosolic Cu, Zn-superoxide
      dismutase (G93A-SOD1) associated with familial amyotrophic lateral sclerosis
      (ALS) demonstrate age-dependent neuroinflammation associated with broad-spectrum
      cytokine, eicosanoid and oxidant production. In order to more precisely study the
      cellular mechanisms underlying glial activation in the G93A-SOD1 mouse, primary
      astrocytes were cultured from 7 day mouse neonates. At this age, G93A-SOD1 mice
      demonstrated no in vivo hallmarks of neuroinflammation. Nonetheless astrocytes
      cultured from G93A-SOD1 (but not wild-type human SOD1-expressing) transgenic
      mouse pups demonstrated a significant elevation in either the basal or the tumor
      necrosis alpha (TNFalpha)-stimulated levels of proinflammatory eicosanoids
      prostaglandin E2 (PGE2) and leukotriene B4 (LTB4); inducible nitric oxide
      synthase (iNOS) and *NO (indexed by nitrite release into the culture medium); and
      protein carbonyl products. Specific cytokine- and TNFalpha death-receptor
      associated components were similarly upregulated in cultured G93A-SOD1 cells as
      assessed by multiprobe ribonuclease protection assays (RPAs) for their mRNA
      transcripts. Thus, endogenous glial expression of G93A-SOD1 produces a metastable
      condition in which glia are more prone to enter an activated neuroinflammatory
      state associated with broad-spectrum increased production of paracrine-acting
      substances. These findings support a role for active glial involvement in ALS and
      may provide a useful cell culture tool for the study of glial inflammation.

PMID- 16436207
TI  - Are fast food restaurants an environmental risk factor for obesity?
AB  - OBJECTIVE: Eating at "fast food" restaurants has increased and is linked to
      obesity. This study examined whether living or working near "fast food"
      restaurants is associated with body weight. METHODS: A telephone survey of 1033
      Minnesota residents assessed body height and weight, frequency of eating at
      restaurants, and work and home addresses. Proximity of home and work to
      restaurants was assessed by Global Index System (GIS) methodology. RESULTS:
      Eating at "fast food" restaurants was positively associated with having children,
      a high fat diet and Body Mass Index (BMI). It was negatively associated with
      vegetable consumption and physical activity. Proximity of "fast food" restaurants
      to home or work was not associated with eating at "fast food" restaurants or with
      BMI. Proximity of "non-fast food" restaurants was not associated with BMI, but
      was associated with frequency of eating at those restaurants. CONCLUSION: Failure
      to find relationships between proximity to "fast food" restaurants and obesity
      may be due to methodological weaknesses, e.g. the operational definition of "fast
      food" or "proximity", or homogeneity of restaurant proximity. Alternatively, the
      proliferation of "fast food" restaurants may not be a strong unique cause of
      obesity.

PMID- 16436206
TI  - Diagnostic role of new Doppler index in assessment of renal artery stenosis.
AB  - BACKGROUND: Renal artery stenosis (RAS) is one of the main causes of secondary
      systemic arterial hypertension. Several non-invasive diagnostic methods for RAS
      have been used in hypertensive patients, such as color Doppler ultrasound (US).
      The aim of this study was to assess the sensitivity and specificity of a new
      renal Doppler US direct-method parameter: the renal-renal ratio (RRR), and
      compare with the sensitivity and specificity of direct-method conventional
      parameters: renal peak systolic velocity (RPSV) and renal aortic ratio (RAR), for
      the diagnosis of severe RAS. METHODS: Our study group included 34 patients with
      severe arterial hypertension (21 males and 13 females), mean age 54 (+/- 8.92)
      years old consecutively evaluated by renal color Doppler ultrasound (US) for
      significant RAS diagnosis. All of them underwent digital subtraction
      arteriography (DSA). RAS was significant if a diameter reduction > 50% was found.
      The parameters measured were: RPSV, RAR and RRR. The RRR was defined as the ratio
      between RPSV at the proximal or mid segment of the renal artery and RPSV measured
      at the distal segment of the renal artery. The sensitivity and specificity cutoff
      for the new RRR was calculated and compared with the sensitivity and specificity
      of RPSV and RAR. RESULTS: The accuracy of the direct method parameters for
      significant RAS were: RPSV >200 cm/s with 97% sensitivity, 72% specificity, 81%
      positive predictive value and 95% negative predictive value; RAR >3 with 77%
      sensitivity, 90% specificity, 90% positive predictive value and 76% negative
      predictive value. The optimal sensitivity and specificity cutoff for the new RRR
      was >2.7 with 97% sensitivity (p < 0.004) and 96% specificity (p < 0.02), with
      97% positive predictive value and 97% negative predictive value. CONCLUSION: The
      new RRR has improved specificity compared with the direct method conventional
      parameters (RPSV >200cm/s and RAR >3). Both RRR and RPSV show better sensitivity
      than RAR for the RAS diagnosis.

PMID- 16436208
TI  - The Readiness Ruler as a measure of readiness to change poly-drug use in drug
      abusers.
AB  - Readiness to change is a crucial issue in the treatment of substance use
      disorders. Experiences with methadone maintenance treatment (MMT) has shown that
      continuous drug and alcohol use with all its consequences characterize most MMT
      programs. In a prospective study of drug abusers seeking opiate agonist
      maintenance treatment in the City of Copenhagen, subjects were administered the
      Addiction Severity Index, and the Readiness Ruler for each of 11 different licit
      and illicit drugs by research technicians. Data was collected upon admission to
      the program and at a 18 month follow-up. Subjects who indicated they wanted to
      quit or cut down upon admission, reported less drug use at 18 month follow-up,
      after controlling for severity of drug problems at intake. Subjects who expressed
      readiness to change their drug use upon admission decreased their drug use. It is
      concluded that the Readiness Ruler measures a construct related to actual
      readiness, supporting its use in the clinical context.

PMID- 16436209
TI  - Is there a relationship between sperm chromosome abnormalities and sperm
      morphology?
AB  - This review explores the relationship between sperm chromosomal constitution and
      morphology. With the advent of techniques for obtaining information on the
      chromosome complements of spermatozoa, this relationship has been studied in
      fertile men and in men with a high frequency of chromosomal abnormalities. Using
      human sperm karyotype analysis, no relationship between sperm chromosome
      abnormalities and morphology was found in fertile men, translocation carriers or
      post-radiotherapy cancer patients. Fluorescence in situ hybridization (FISH)
      analysis has not generally revealed a specific association between
      morphologically abnormal sperm and sperm chromosome abnormalities, but has
      indicated that teratozoospermia, like other forms of abnormal semen profiles
      (aesthenozoospermia, oligozoospermia) is associated with a modest increase in the
      frequency of sperm chromosome abnormalities. However, FISH studies on some
      infertile men and mouse strains have suggested that certain types of
      morphologically abnormal spermatozoa, such as macrocephalic multitailed
      spermatozoa, are associated with a very significantly increased frequency of
      aneuploidy. Thus, there may be an association between sperm morphology and
      aneuploidy in infertile men with specific abnormalities.

PMID- 16436210
TI  - Genome-wide acceleration of protein evolution in flies (Diptera).
AB  - BACKGROUND: The rate of molecular evolution varies widely between proteins, both
      within and among lineages. To what extent is this variation influenced by genome
      wide, lineage-specific effects? To answer this question, we assess the rate
      variation between insect lineages for a large number of orthologous genes.
      RESULTS: When compared to the beetle Tribolium castaneum, we find that the stem
      lineage of flies and mosquitoes (Diptera) has experienced on average a 3-fold
      increase in the rate of evolution. Pairwise gene comparisons between Drosophila
      and Tribolium show a high correlation between evolutionary rates of orthologous
      proteins. CONCLUSION: Gene specific divergence rates remain roughly constant over
      long evolutionary times, modulated by genome-wide, lineage-specific effects.
      Among the insects analysed so far, it appears that the Tribolium genes show the
      lowest rates of divergence. This has the practical consequence that homology
      searches for human genes yield significantly better matches in Tribolium than in
      Drosophila. We therefore suggest that Tribolium is better suited for comparisons
      between phyla than the widely employed dipterans.

PMID- 16436211
TI  - BLAST screening of chlamydial genomes to identify signature proteins that are
      unique for the Chlamydiales, Chlamydiaceae, Chlamydophila and Chlamydia groups of
      species.
AB  - BACKGROUND: Chlamydiae species are of much importance from a clinical viewpoint.
      Their diversity both in terms of their numbers as well as clinical involvement
      are presently believed to be significantly underestimated. The obligate
      intracellular nature of chlamydiae has also limited their genetic and biochemical
      studies. Thus, it is of importance to develop additional means for their
      identification and characterization. RESULTS: We have carried out analyses of
      available chlamydiae genomes to identify sets of unique proteins that are either
      specific for all Chlamydiales genomes, or different Chlamydiaceae family members,
      or members of the Chlamydia and Chlamydophila genera, or those unique to
      Protochlamydia amoebophila, but which are not found in any other bacteria. In
      total, 59 Chlamydiales-specific proteins, 79 Chlamydiaceae-specific proteins, 20
      proteins each that are specific for both Chlamydia and Chlamydophila and 445 ORFs
      that are Protochlamydia-specific were identified. Additionally, 33 cases of
      possible gene loss or lateral gene transfer were also detected. CONCLUSION: The
      identified chlamydiae-lineage specific proteins, many of which are highly
      conserved, provide novel biomarkers that should prove of much value in the
      diagnosis of these bacteria and in exploration of their prevalence and diversity.
      These conserved protein sequences (CPSs) also provide novel therapeutic targets
      for drugs that are specific for these bacteria. Lastly, functional studies on
      these chlamydiae or chlamydiae subgroup-specific proteins should lead to
      important insights into lineage-specific adaptations with regards to development,
      infectivity and pathogenicity.

PMID- 16436212
TI  - Selective migration of neuralized embryonic stem cells to stem cell factor and
      media conditioned by glioma cell lines.
AB  - BACKGROUND: Pluripotent mouse embryonic stem (ES) cells can be induced in vitro
      to become neural progenitors. Upon transplantation, neural progenitors migrate
      toward areas of damage and inflammation in the CNS. We tested whether
      undifferentiated and neuralized mouse ES cells migrate toward media conditioned
      by glioma cell lines (C6, U87 & N1321) or Stem Cell Factor (SCF). RESULTS: Cell
      migration assays revealed selective migration by neuralized ES cells to
      conditioned media as well as to synthetic SCF. Migration of undifferentiated ES
      cells was extensive, but not significantly different from that of controls
      (Unconditioned Medium). RT-PCR analysis revealed that all the three tumor cell
      lines tested synthesized SCF and that both undifferentiated and neuralized ES
      cells expressed c-kit, the receptor for SCF. CONCLUSION: Our results demonstrate
      that undifferentiated ES cells are highly mobile and that neural progenitors
      derived from ES cells are selectively attracted toward factors produced by
      gliomas. Given that the glioma cell lines synthesize SCF, SCF may be one of
      several factors that contribute to the selective migration observed.

PMID- 16436213
TI  - Protein structure similarity from Principle Component Correlation analysis.
AB  - BACKGROUND: Owing to rapid expansion of protein structure databases in recent
      years, methods of structure comparison are becoming increasingly effective and
      important in revealing novel information on functional properties of proteins and
      their roles in the grand scheme of evolutionary biology. Currently, the
      structural similarity between two proteins is measured by the root-mean-square
      deviation (RMSD) in their best-superimposed atomic coordinates. RMSD is the
      golden rule of measuring structural similarity when the structures are nearly
      identical; it, however, fails to detect the higher order topological similarities
      in proteins evolved into different shapes. We propose new algorithms for
      extracting geometrical invariants of proteins that can be effectively used to
      identify homologous protein structures or topologies in order to quantify both
      close and remote structural similarities. RESULTS: We measure structural
      similarity between proteins by correlating the principle components of their
      secondary structure interaction matrix. In our approach, the Principle Component
      Correlation (PCC) analysis, a symmetric interaction matrix for a protein
      structure is constructed with relationship parameters between secondary elements
      that can take the form of distance, orientation, or other relevant structural
      invariants. When using a distance-based construction in the presence or absence
      of encoded N to C terminal sense, there are strong correlations between the
      principle components of interaction matrices of structurally or topologically
      similar proteins. CONCLUSION: The PCC method is extensively tested for protein
      structures that belong to the same topological class but are significantly
      different by RMSD measure. The PCC analysis can also differentiate proteins
      having similar shapes but different topological arrangements. Additionally, we
      demonstrate that when using two independently defined interaction matrices,
      comparison of their maximum eigenvalues can be highly effective in clustering
      structurally or topologically similar proteins. We believe that the PCC analysis
      of interaction matrix is highly flexible in adopting various structural
      parameters for protein structure comparison.

PMID- 16436214
TI  - Low temperature reduction of hexavalent chromium by a microbial enrichment
      consortium and a novel strain of Arthrobacter aurescens.
AB  - BACKGROUND: Chromium is a transition metal most commonly found in the environment
      in its trivalent [Cr(III)] and hexavalent [Cr(VI)] forms. The EPA maximum total
      chromium contaminant level for drinking water is 0.1 mg/l (0.1 ppm). Many water
      sources, especially underground sources, are at low temperatures (less than or
      equal to 15 Centigrade) year round. It is important to evaluate the possibility
      of microbial remediation of Cr(VI) contamination using microorganisms adapted to
      these low temperatures (psychrophiles). RESULTS: Core samples obtained from a
      Cr(VI) contaminated aquifer at the Hanford facility in Washington were enriched
      in Vogel Bonner medium at 10 Centigrade with 0, 25, 50, 100, 200, 400 and 1000
      mg/l Cr(VI). The extent of Cr(VI) reduction was evaluated using the diphenyl
      carbazide assay. Resistance to Cr(VI) up to and including 1000 mg/l Cr(VI) was
      observed in the consortium experiments. Reduction was slow or not observed at and
      above 100 mg/l Cr(VI) using the enrichment consortium. Average time to complete
      reduction of Cr(VI) in the 30 and 60 mg/l Cr(VI) cultures of the consortium was 8
      and 17 days, respectively at 10 Centigrade. Lyophilized consortium cells did not
      demonstrate adsorption of Cr(VI) over a 24 hour period. Successful isolation of a
      Cr(VI) reducing organism (designated P4) from the consortium was confirmed by 16S
      rDNA amplification and sequencing. Average time to complete reduction of Cr(VI)
      at 10 Centigrade in the 25 and 50 mg/l Cr(VI) cultures of the isolate P4 was 3
      and 5 days, respectively. The 16S rDNA sequence from isolate P4 identified this
      organism as a strain of Arthrobacter aurescens, a species that has not previously
      been shown to be capable of low temperature Cr(VI) reduction. CONCLUSION: A.
      aurescens, indigenous to the subsurface, has the potential to be a predominant
      metal reducer in enhanced, in situ subsurface bioremediation efforts involving
      Cr(VI) and possibly other heavy metals and radionuclides.

PMID- 16436215
TI  - The Tgif2 gene contains a retained intron within the coding sequence.
AB  - BACKGROUND: TGIF and TGIF2 are homeodomain proteins, which act as TGFbeta
      specific Smad transcriptional corepressors. TGIF recruits general repressors
      including mSin3 and CtBP. The related TGIF2 protein functions in a similar
      manner, but does not bind CtBP. In addition to repressing TGFbeta activated gene
      expression, TGIF and TGIF2 repress gene expression by binding directly to DNA.
      TGIF and TGIF2 share two major blocks of similarity, encompassing the
      homeodomain, and a conserved carboxyl terminal repression domain. Here we
      characterize two splice variants of the Tgif2 gene from mouse and demonstrate
      that the Tgif2 gene contains a retained intron. RESULTS: By PCR from mouse cDNA,
      we identified two alternate splice forms of the Tgif2 gene. One splice variant
      encodes the full length 237 amino acid Tgif2, whereas the shorter form results in
      the removal of 39 codons from the centre of the coding region. The generation of
      this alternate splice form occurs with the mouse RNA, but not the human, and both
      splice forms are present in all mouse tissues analyzed. Human and mouse Tgif2
      coding sequences contain a retained intron, which in mouse Tgif2 is removed by
      splicing from around 25-50% of RNAs, as assessed by RT-PCR. This splicing event
      is dependent on sequences within the mouse Tgif2 coding sequence. Both splice
      forms of mouse Tgif2 encode proteins which are active transcriptional repressors,
      and can repress both TGFbeta dependent and independent transcription. In
      addition, we show that human and mouse Tgif2 interact with the transcriptional
      corepressor mSin3. CONCLUSION: These data demonstrate that the Tgif2 gene
      contains a retained intron, within the second coding exon. This retained intron
      is not removed from the human mRNA at a detectable level, but is spliced out in a
      significant proportion of mouse RNAs. This alternate splicing is dependent
      entirely on sequences within the mouse Tgif2 coding sequence, suggesting the
      presence of an exonic splicing enhancer. Both splice forms of mouse Tgif2 produce
      proteins which are functional transcriptional repressors.

PMID- 16436216
TI  - Wealth, mother's education and physical access as determinants of retail sector
      net use in rural Kenya.
AB  - BACKGROUND: Insecticide-treated bed nets (ITN) provide real hope for the
      reduction of the malaria burden across Africa. Understanding factors that
      determine access to ITN is crucial to debates surrounding the optimal delivery
      systems. The influence of homestead wealth on use of nets purchased from the
      retail sector is well documented, however, the competing influence of mother's
      education and physical access to net providers is less well understood. METHODS:
      Between December 2004 and January 2005, a random sample of 72 rural communities
      was selected across four Kenyan districts. Demographic, assets, education and net
      use data were collected at homestead, mother and child (aged < 5 years) levels.
      An assets-based wealth index was developed using principal components analysis,
      travel time to net sources was modelled using geographic information systems, and
      factors influencing the use of retail sector nets explored using a multivariable
      logistic regression model. RESULTS: Homestead heads and guardians of 3,755
      children < 5 years of age were interviewed. Approximately 15% (562) of children
      slept under a net the night before the interview; 58% (327) of the nets used were
      purchased from the retail sector. Homestead wealth (adjusted OR = 10.17, 95% CI =
      5.45-18.98), travel time to nearest market centres (adjusted OR = 0.51, 95% CI =
      0.37-0.72) and mother's education (adjusted OR = 2.92, 95% CI = 1.93-4.41) were
      significantly associated with use of retail sector nets by children aged less
      than 5 years. CONCLUSION: Approaches to promoting access to nets through the
      retail sector disadvantage poor and remote communities where mothers are less
      well educated.

PMID- 16436217
TI  - Influence of the atrio-ventricular delay optimization on the intra left
      ventricular delay in Cardiac Resynchronization Therapy.
AB  - BACKGROUND: Cardiac Resynchronization Therapy (CRT) leads to a reduction of left
      ventricular dyssynchrony and an acute and sustained hemodynamic improvement in
      patients with chronic heart failure. Furthermore, an optimized AV-delay leads to
      an improved myocardial performance in pacemaker patients. The focus of this study
      is to investigate the acute effect of an optimized AV-delay on parameters of
      dyssynchrony in CRT patients. METHOD: 11 chronic heart failure patients with CRT
      who were on stable medication were included in this study. The optimal AV-delay
      was defined according to the method of Ismer (mitral inflow and trans-oesophageal
      lead). Dyssynchrony was assessed echocardiographically at three different
      settings: AVDOPT; AVDOPT-50 ms and AVDOPT+50 ms. Echocardiographic assessment
      included 2D- and M-mode echo for the assessment of volumes and hemodynamic
      parameters (CI, SV) and LVEF and tissue Doppler echo (strain, strain rate, Tissue
      Synchronisation Imaging (TSI) and myocardial velocities in the basal segments)
      RESULTS: The AVDOPT in the VDD mode (atrially triggered) was 105.5 +/- 38.1 ms
      and the AVDOPT in the DDD mode (atrially paced) was 186.9 +/- 52.9 ms. Intra
      individually, the highest LVEF was measured at AVDOPT. The LVEF at AVDOPT was
      significantly higher than in the AVDOPT-50 setting (p = 0.03). However, none of
      the parameters of dyssynchrony changed significantly in the three settings.
      CONCLUSION: An optimized AV delay in CRT patients acutely leads to an improved
      systolic left ventricular ejection fraction without improving dyssynchrony.

PMID- 16436218
TI  - Australian multicentre comparison of subtyping methods for the investigation of
      Campylobacter infection.
AB  - In order to identify subtyping methods able to contribute to the surveillance or
      investigation of Australian Campylobacter infection, six genotypic and three
      phenotypic subtyping methods were evaluated on a collection of 84 clinical
      isolates collected over a 30-month period from one region in Australia. The aim
      was to compare the logistics of various subtyping methods and examine their
      ability to assist in finding outbreaks or common sources of sporadic infection.
      The genotypic subtyping methods used were sequencing of the short variable region
      of the flaA gene, two methods using restriction fragment length polymorphism
      (RFLP) of the flaA gene using either DdeI or EcoRI with PstI, automated
      ribotyping, pulsed field gel electrophoresis and multilocus sequence typing. The
      phenotypic methods employed included Laboratory of Enteric Pathogens serotyping,
      Lior biotyping and antibiotic resistotyping. The level of agreement between
      subtyping results was determined. Phenotypic methods showed little agreement
      whereas genotypic typing methods showed a high level of agreement. Using the
      premise that five of the six genotypic typing methods were in agreement 15
      genotypic groupings were identified. Sequencing of the short variable region of
      the flaA gene, RFLP of the flaA gene or automated ribotyping in conjunction with
      multilocus sequence typing best identified genotypic groupings. An alternative
      combination of RFLP of the flaA gene followed by ribotyping was equally
      satisfactory. RFLP of the flaA gene appeared to be suitable as a preliminary
      typing method based on ease of operation, equipment availability and cost.

PMID- 16436219
TI  - Seroepidemiology of hepatitis A and hepatitis B virus in Luxembourg.
AB  - A prospective seroepidemiological survey was carried out in Luxembourg in 2000
      2001 to determine the antibody status of the Luxembourg population against
      hepatitis A virus (HAV) and hepatitis B virus (HBV). One of the objectives of
      this survey was to assess the impact of the hepatitis B vaccination programme,
      which started in May 1996 and included a catch-up campaign for all adolescents
      aged 12-15 years. Venous blood from 2679 individuals was screened for the
      presence of antibodies to HAV antigen and antibodies to hepatitis B surface
      antigen (anti-HBs) using an enzyme immunoassay. Samples positive for anti-HBs
      were tested for antibody to hepatitis B core antigen (anti-HBc) using a
      chemiluminiscent microparticle immunoassay to distinguish between individuals
      with past exposure to vaccine or natural infection. The estimated age
      standardized anti-HAV seroprevalence was 42.0% [95% confidence interval (CI) 39.8
      44.1] in the population >4 years of age. Seroprevalence was age-dependent and
      highest in adult immigrants from Portugal and the former Yugoslavia. The age
      standardized prevalence of anti-HBs and anti-HBc was estimated at 19.7% (95% CI
      18.1-21.3) and 3.16% (95% CI 2.2-4.1) respectively. Anti-HBs seroprevalence
      exceeding 50% was found in the cohorts targeted by the routine hepatitis B
      vaccination programme, which started in 1996. Our study illustrates that most
      young people in Luxembourg are susceptible to HAV infection and that the
      hepatitis B vaccination programme is having a substantial impact on population
      immunity in children and teenagers.

PMID- 16436220
TI  - Domestic and travel-related foodborne gastrointestinal illness in a population
      health survey.
AB  - Routine surveillance data underestimate incidence of foodborne gastrointestinal
      (FGI) illness and provide little information on illness related to travel. We
      analysed data from the Welsh Health Survey to estimate population incidence, and
      to examine risk factors for FGI and factors associated with consulting a doctor.
      Reported frequency of any FGI in the 3 months before interview was 20.0% [95%
      confidence interval (CI) 19.5-20.4; equivalent to 0.8 episodes per person-year],
      and for travel-related FGI was 1.6% (95% CI 1.5-1.8). In the final model, sex,
      age group, marital status, self-reported health, long-term illness, smoking and
      alcohol consumption were all independent predictors of FGI. People who consulted
      a doctor were likely to be older, in poorer health, taking regular medication, or
      to report mental illness. FGI is common but risk factors for illness and
      consultation differ and impressions of the epidemiology of the disease based on
      surveillance data are therefore distorted.

PMID- 16436221
TI  - Distribution of molecular subtypes within Salmonella enterica serotype
      Enteritidis phage type 4 and S. Typhimurium definitive phage type 104 in nine
      European countries, 2000-2004: results of an international multi-centre study.
AB  - This study investigates the distribution of pulsed-field gel electrophoresis
      (PFGE) profiles within Salmonella enterica serotype Enteritidis phage type (PT) 4
      and S. Typhimurium definitive phage type (DT) 104, from cases of human infection
      in nine European countries from 2000 to 2004. Isolates were subtyped using
      standardized methods and gel images submitted by each participating country to
      the coordinating centre (Health Protection Agency Centre for Infections, London,
      UK), where they were entered into a central database, developed within
      BioNumerics software, and designated using an agreed nomenclature. S. Enteritidis
      PT4 (n=3637) was differentiated into 38 different profiles. Simpson's index of
      diversity (D) of profiles ranged from 0.2 to 0.4. Profile SENTXB.0001 represented
      at least 80% of all profiles in each country. S. Typhimurium DT104 (n=1202) was
      differentiated into 28 different profile types. Simpson's D was at least 0.6 in
      all countries except in Austria and Italy. In both these countries over 74% of S.
      Typhimurium DT104 profiles were STYMXB.0013. Profile STYMXB.0061, was predominant
      in Denmark, Spain, Finland and England and Wales where it represented between 36%
      and 45% of profiles. Profile STYMXB.0001 represented nearly half of all profiles
      in Scotland and 23% in England and Wales. PFGE is proving useful for further
      discrimination within S. Enteritidis PT4 and S. Typhimurium DT104. Ascertainment
      of international outbreaks involving common serotypes and phage types may be
      increased by the timely pooling of PFGE profiles within a central database
      readily accessible to all participating countries.

PMID- 16436222
TI  - [The managerial education of nurse coordinator and the educational contract: the
      experience of the First Level Master in Nursing Management for Coordinational
      Functions at the Catholic University of Rome].
AB  - Changes in the National Health Service (NHS), in nursing laws and education made
      necessary a first level Master to teach nurses managerial competences for
      coordinational functions. Nowadays nurse coordinator are important in health
      organization in order to transform individual knowledges of nurses in effective,
      efficient and appropriate care practice. The project of the First Level Master in
      Nursing Management for Coordinational Functions run at the Catholic University of
      Rome, kept into consideration changes in NHS, nursing laws and education. The
      Master was made of four modules in order to teach learning specific competences.
      The Pedagogy of the Contract was used to guide the training. A Form based on the
      Pedagogy of the Contract was developed. This Form helped in defining the training
      objectives and their evaluation. The Model of the Reflection about the Experience
      and the presence of a tutor were used to integrate education with training
      settings. This Master emphasized the current functions of the nurse coordinator
      such as problem solving, direction, organization and mainly the management of
      knowledge of coordinated nurses.

PMID- 16436223
TI  - [Mobbing at work].
AB  - The social psychology has studied the dynamics present in the groups (of work and
      not) since years 60s: the canalization of the aggressiveness of the group towards
      some individuals, the conflicts, the theirs administration, the mechanisms of
      expulsion of the group. The psychology of the work, has studied, those dynamics,
      in the world of the firms. Lately, the reality of the work has changed. Recently
      the organizational transformations (fusions) lived in Italy, the flexibility of
      the work, has caused an exuberance of staff, often not easily administered. The
      psychologic working violence expanded, generating unemployed persons and becoming
      a kind of short cut for the firms that, in this way, succeed to resign become
      inconvenient subordinates. Every day, inside of the firms, a some number of able,
      capable, responsible and motivated workers bear situations of moral troubles or,
      as is custom to name them in these years of mobbing.

PMID- 16436225
TI  - [Burnout and mobbing risk for health professionals].
AB  - Burnout is one important consequence of worker stress and is associated with
      lower moral, reduced job performance, low productivity, absenteeism, job
      turnover. The aim of this study was to evaluate the burnout level and all its
      related aspects among health professionists in the Rimini county. All personnel
      described their experiences in the Maslach Burnout Inventory test (791
      questionnaires) and in the Mobbing Perception test (791 questionnaires). The
      median age of the workers was 38.5 years, 151 were male and 640 female, about 93%
      were full time workers. On average health professionists reported to have a good
      relationship with patients, a good work expectations but to experience a
      relatively high stress index. This study underlined the importance to improve
      occupational conditions adopting staff-support interventions for the management
      of stress and conflicts among heath operators.

PMID- 16436224
TI  - [Mobbing in nursing: a survey results in Tuscany].
AB  - This article will present mobbing in its different aspects and consequences with
      reference to its manifestations in sanitarian organizations and in nursing. It
      springs out from wish to inquire into a phenomenon which generates
      uncomfortableness and embarrassment; it springs out from wish to know what it is
      and because it frights; it springs out from wish to understand it, to defend
      oneselves against it and to keep out it. It springs out from curiosity to know if
      it is present in nursing and eventually how much is its entity. The cognitive
      research takes place in a Tuscan Sanitary Factory.

PMID- 16436226
TI  - [Multidimensional evaluation: an example to be applied in dialysis].
AB  - Between June and July 2005 we submitted the IPPE survey (Pluridimensional Record
      for Hemodialysis Patient) to 61 chronic hemodialysis patients of our Centre. The
      aim of the survey was to estimate the six most important components in the life
      of patients undergoing chronic dialysis: familiar relationships, relationship
      with their own body, need of drinking, daily life, general needs, disease
      perception. The most critical factor is the need of drinking, followed by the
      problems about body feelings and daily life. Disease perception and familiar
      relationships seem to be less important problems. Regarding patients needs of
      medical and nursing care and about the condition of in-hospital patient, there is
      a strong lack of information about diagnosis (72%), a high request of better
      discussion with doctors (69%) and the need of a greater involvement in the
      therapeutic choices (57%), related to the difficult communication between doctor
      and patient. 30% of the interviewed patients would like to have more attention by
      the nurses: this aspect is not due to the absence of the nurse but rather to a
      lack of empathy between nurse and patient. These data should be seen as a reason
      for improving medical and nursing care, because being aware of problems is the
      first step to their solution.

PMID- 16436227
TI  - [A picture of the Italian nursing scientific literature as a result of nursing
      journal analysis. First part: 1978-1997].
AB  - This is the result of a revision of what Italian nurses have written from 1978 to
      1997 in Nursing Journals. Four well known Nursing Journals have been selected and
      taken into consideration: two are the only nursing refereed journals in the
      Country (one is a nursing Association official journal), one is the official
      journal of the National nursing Statutory Body and one is a specialty nursing
      Group journal. Articles has been divided into seven categories and results show
      that Italian nurses lack in the continuity of writing. Research and theory are
      the sectors where nurses write less.

PMID- 16436228
TI  - [A picture of the Italian nursing scientific literature as a result of nursing
      journals analysis. (part 2) 1998-2003].
AB  - This article analyzes the Italian scientific Nursing production published on five
      National Nursing Journals from 1978 to 2003 it is the second part of the article
      in the antecedents pages. Results are showing that the Nursing literature
      production as it appears from dedicated Journals, is following a constant
      development. Of course each Journal has its own characteristics and specificity
      but in general more articles than in the past (1978-1998) are presenting research
      methodology discussions and reports of research conducted in the Nursing field.
      Few articles, considering the total, discuss conceptualization or theorization of
      Nursing but anyway, there is a visible movement in advance compared with the past
      considered period (1978-1998).

PMID- 16436229
TI  - [Survey of what is published on Italian nursing journals].
AB  - Nursing research is an important activity for nurses; the main aim is to improve
      the quality of nursing. Several national and european laws have been issued about
      it. To develop knowledge about nursing, nurses have to understand the results of
      researches, implement them in the different situation and sometimes carry out
      researches. The results can be published in nursing journals which a lot of
      nurses use to share information. This study reviewed the characteristics of
      research articles published in italian nursing journals from 1998 to 2003.
      Phenomena of interest are: areas of enquiry, investigators, methods, research
      design, sampling and means to gather data. 122 articles have been reviewed: 78%
      focus on clinical aspects, 55% were carry out by nurses, 92% adopt the
      quantitative approach, 90% used non experimental design, 89% used convenience
      selection sampling method and 58% answer ways. The characteristics of this study
      are similar to other studies about italian nursing publication. There are some
      limits in this type of literature: lower generalization because of lower
      representativeness of sample, convenience selection sampling method, and higher
      risk of interference due to frequent use of non experimental design. However the
      number of italian nurses that carry out researches is increasing and nursing is
      the most studied area.

PMID- 16436233
TI  - [Increasing problems with invasive fungal infections in Denmark].

PMID- 16436234
TI  - [Proton magnetic resonance spectroscopy in the evaluation of cognitive
      disturbances].
AB  - Magnetic resonance spectroscopy can detect metabolic changes in the brain,
      including changes in N-acetyl aspartate, a metabolite generally believed to be a
      marker of neuronal integrity. The correlations between metabolic changes and
      cognitive status in normal subjects and in a range of neurological and
      psychiatric disorders are reviewed. Magnetic resonance spectroscopy seems to be a
      way to monitor the efficacy of existing and new treatments to prevent the
      development of cognitive deficits in a number of diseases.

PMID- 16436235
TI  - [Non-steroidal anti-inflammatory agents and prevention of colorectal adenomas and
      carcinomas].

PMID- 16436236
TI  - [Candidemia in the hospitals in the Aarhus County, Denmark, 1993-2002].
AB  - INTRODUCTION: During recent years a rise in the occurrence of candidaemia has
      been reported in the USA as well as in Europe, and especially in intensive care
      units (ICUs). The aim of this study was to describe the frequency of candidaemia
      and related Candida infections in the hospitals of Aarhus County, Denmark, from
      1993 to 2002, and to assess possible causal factors, among these the consumption
      of antimicrobial agents. MATERIALS AND METHODS: The material included blood
      cultures carried out at the Department of Clinical Microbiology, Aarhus
      University Hospital (AUH), during the study period, plus Candida-positive
      cultures from other normally sterile sites from patients with candidaemia.
      Microbiological findings were compiled from our laboratory information system,
      MADS. Information regarding the use of antimicrobial agents in the hospitals of
      Aarhus County was obtained from the University Hospital pharmacy and the Danish
      Medicines Agency Web site. RESULTS: During the study period the fraction of
      positive blood cultures was constant, while the fraction of positive cultures
      yielding Candida species increased from 1.8% to 3.4%, with an especially marked
      increase among patients in AUH. An increase in the proportion of Candida non
      albicans species compared to C. albicans was noted, and it was also noted that
      the consumption of antimicrobial agents had risen markedly during the period.
      DISCUSSION: The present study adds to the assumption of a causal relationship
      between candidaemia and the use of antimicrobials and foreign bodies.

PMID- 16436237
TI  - [Long-term disease in Danish children reported by the parents].
AB  - INTRODUCTION: The aim of this study was to report the prevalence and nature of
      long-term diseases and their consequences in children under the age of 16 in
      Denmark, and to identify the socio-demographic determinants of disease. MATERIALS
      AND METHODS: Parents and stepparents participating in the Danish Health and
      Morbidity Survey, 2000, were interviewed at home about long-term diseases,
      including impairments and sequelae after injury and disease, in children under
      the age of 16 living at home. Answers were given for 7,670 children, and diseases
      were coded according to ICD-10 by two doctors. Logistic regression analysis was
      used to identify the determinants and consequences of disease. RESULTS: A total
      of 16.2% of children had one or more long-term diseases, boys (17.5%) more
      frequently than girls (14.8%). The prevalence increased through the first six
      years of life. A social gradient was seen: children of parents with low
      socioeconomic status or with little education had a higher prevalence. The most
      frequent disease was asthma (4.9%). Also frequent were congenital disorders
      (1.6%), otitis media (1.4%) and hearing impairment (0.6%). Children with long
      term disease suffered more frequently than others from poor health in general,
      recent sick leave and poor thriving. DISCUSSION: The figures for long-term
      disease reported by the parents participating in the study were in accordance
      with what was found in earlier studies, but stigmatising and less severe
      diseases, as well as periodically recurring diseases, were probably
      underreported. Attention should be paid to the high prevalence of asthma, to the
      poorer thriving and to the general health status of children with long-term
      disease, and to the social inequality in children's health.

PMID- 16436238
TI  - [Prevalence rates of recent illnesses in Danish children, 1994 and 2000].
AB  - INTRODUCTION: This study aims to describe the prevalence, types and seasonal
      variation of recent illnesses in Danish children in 1994 and 2000, and to
      identify their determinants. MATERIALS AND METHODS: Participants in the Danish
      Health and Morbidity Survey, 1994 and 2000, were interviewed about the illnesses
      during the previous 14 days of the children under age 16 living at home. Answers
      were given for 2,136 children in 1994 and 7,670 in 2000. The data were weighted
      to provide a nationally representative sample. The illnesses were grouped into
      ten categories. Logistic regression analysis was used to identify determinants.
      RESULTS: The prevalence rate for recent illness did not differ significantly
      between 1994 and 2000 (13.4-14.0%), but for fever and influenza it increased from
      1994 to 2000 (from 1.9% to 3.0%), and in boys from 1 to 2 years of age the total
      illness rate increased significantly (from 26.7% to 31.9%). Attendance at day
      care increased the prevalence of recent illness in those 0-2 years old. In 2000,
      the age-specific prevalence rates were: 0 years: 21.2%, 1-2 years: 29.0%, 3-5
      years: 15.7%, 6-8 years: 9.3%, 9-12 years: 9.3% and 13-15 years: 11.5%. The
      prevalence rates were highest in the January-March quarter: 18.9%. The specific
      illness rates were: cold/sore throat: 4.5%; fever/influenza: 3.0%;
      gastrointestinal infection: 1.9%; middle ear infection: 1.3%, lower respiratory
      infection/asthma: 1.1%; skin disease: 0.6%; conjunctivitis: 0.4%; headache: 0.4%;
      injury: 0.3%; other: 0.9%. DISCUSSION: The rising trend is due in particular to
      an influenza epidemic in 2000. The high prevalence of infections in 1-to-2-year
      olds underscores the need to decrease the spread of infections in day care and to
      avoid the most vulnerable infants' being cared for along with many other
      children.

PMID- 16436239
TI  - [Local overpressure treatment reduces vestibular symptoms in patients with
      Meniere's disease--secondary publication. A clinically randomised multicenter
      double-blind placebo-controlled study].
AB  - This investigation was performed to evaluate the efficacy of a new device, the
      Meniett, in the treatment of Meniere's disease. The device delivers pressure
      pulses to the middle ear through a ventilating tube in the tympanic membrane.
      These pressure changes are conveyed to the inner ear, reducing the endolymphatic
      hydrops. The device is significantly effective in reducing the vestibular
      symptoms, as compared with the placebo device. Local overpressure treatment is a
      novel treatment that is non-invasive, non-destructive and safe. It should be
      offered to patients before more invasive surgical modalities are suggested.

PMID- 16436240
TI  - [OPUS: a randomised multicenter trial of integrated versus standard treatment for
      patients with a first-episode psychosis--secondary publication].
AB  - A total of 547 patients with first-episode psychosis were included in a
      randomised clinical trial comparing integrated treatment with standard treatment.
      The integrated treatment consisted of assertive community treatment with
      programmes for family involvement and social skills training. Patients in
      integrated treatment had significantly fewer psychotic and negative symptoms,
      less comorbid substance abuse, better adherence to treatment and more
      satisfaction with treatment at one-year and two-year follow-ups.

PMID- 16436241
TI  - [Ascariasis is a zoonosis in Denmark--secondary publication].
AB  - It has been claimed that Danish cases of human ascariasis have been acquired
      either during travel to other countries or through consumption of untreated food
      imported from areas where human ascariasis is endemic. An epidemiological survey
      in Viborg County indicated, however, that pigs are the primary source of the
      infection. Our population-genetic investigations have now confirmed this
      hypothesis. The main transmission route for human ascariasis in developed
      countries therefore seems to be from pigs to people; thus, it is essential that
      contact with pig manure be avoided, especially by young children.

PMID- 16436242
TI  - [Proximal tibial epiphysiolysis in a young gymnast due to hyperflexion trauma].
AB  - The authors present an unusual case of upper tibial epiphysiolysis due to
      hyperflexion trauma. The patient was operated on by removal of interposed
      periosteum and fixation by crossed Kirchner wires. Knowledge of the mechanism of
      trauma and the direction of the force of the trauma is essential to the planning
      of the surgical approach and awareness of possible complications.

PMID- 16436243
TI  - [Management of patients with myocardial rupture after acute myocardial
      infarction].
AB  - Ventricular free wall rupture resulting in pericardial tamponade and shock is a
      known complication of myocardial infarction. In recent years, the widespread
      availability of echocardiographia has enabled prompt diagnosis. We report a
      patient with left ventricular free wall rupture in its most severe form who
      survived after surgical intervention. We point out the importance of rapid and
      precise diagnosis through echocardiographia. The presence of pericardial
      haematoma/fluid, haematoma in the ventricular wall or compression of the
      ventricles supports this diagnosis. Echocardiographia is an important tool for
      verifying the diagnosis in this group of patients.

PMID- 16436244
TI  - [Strangulation of the small bowel due to a defect in the broad ligament].
AB  - A defect in the broad ligament may be congenital or acquired. Due to such a
      defect, an internal hernia may develop. This usually involves the small bowel. We
      report a case of internal herniation of the small bowel due to a defect in the
      broad ligament diagnosed perioperatively. Computerized tomography is helpful in
      preoperative diagnosis of the condition and should be considered if the condition
      is suspected clinically. The defect should be closed surgically.

PMID- 16436255
TI  - [Patient insurance activities].

PMID- 16436270
TI  - Attributional style in psychosis--the role of affect and belief type.
AB  - People holding persecutory beliefs have been hypothesised to show a self-serving
      attributional style, which functions to protect self-esteem Bentall, Corcoran,
      Howard, Blackwood, and Kinderman (2001). Experimental support for this has been
      mixed. Freeman et al. (1998) suggested depressed and grandiose subgroups of those
      with persecutory beliefs might explain events differently. In this study, 71
      participants completed measures of delusional beliefs, depression and
      attributional style. We hypothesised that those with persecutory beliefs would
      form grandiose and depressed subgroups, and that a self-serving attributional
      style would characterise only the grandiose subgroup. Hypotheses were partially
      confirmed. Clear subgroups were evident and only those with both persecutory and
      grandiose beliefs showed an externalising attributional style for negative
      events. Depression, irrespective of co-occurring persecutory beliefs, was related
      to a reduced self-serving bias and an externalising attributional style for
      positive events. On their own, persecutory beliefs were not related to any
      particular attributional style. Depressed and grandiose subgroups of those with
      persecutory beliefs might account for some of the inconsistencies in the
      attribution literature. Even within a single symptom group, care should be taken
      in both research and therapy to consider individual symptom patterns.

PMID- 16436271
TI  - The pattern of deoxycytidine- and deoxyguanosine kinase activity in relation to
      messenger RNA expression in blood cells from untreated patients with B-cell
      chronic lymphocytic leukemia.
AB  - Deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) catalyze the first
      step in the intracellular cascade of fludarabine (2-fluoroadenine-beta-D
      arabinofuranoside) and cladribine (2-chlorodeoxyadenosine) phosphorylation, which
      leads to activation of these prodrugs, commonly used for treatment of chronic
      lymphocytic leukemia (CLL). Thus, resistance to nucleoside analogues may
      primarily be due to low levels of deoxynucleoside kinase activity. The purpose of
      this study was to investigate the activity profiles of dCK and dGK and
      characterize the possible relationship between the levels of dCK enzymatic
      activities and mRNA levels in B-CLL cells from untreated patient samples in an
      attempt to determine the best approach for predicting sensitivity to nucleoside
      analogues and thereby optimizing treatment of CLL. For this purpose, dCK and dGK
      analyses were done in blood cells from 59 untreated symptomatic patients with
      CLL. The dGK activity towards 2-chlorodeoxyadenosine was significantly lower than
      of dCK (median 73 pmol/mg protein/min (85-121, 95% CI) versus 353 pmol/mg
      protein/min (331-421)). The median dCK mRNA level was 0.107 (0.096-0.120, 95%
      CI). There was a lack of correlation between the activities of dCK and dGK, which
      indicates that these proteins are regulated independently. We also found that the
      dCK and dGK activity measurement towards their endogenous substrates were
      comparable to the nucleoside analogues tested. Such variations in enzyme
      activities and mRNA levels may well explain differences in clinical responses to
      treatment. There was no correlation between the levels of dCK mRNAs and enzymatic
      activities using a quantitative real-time PCR procedure. Sequencing of dCK mRNA
      did not reveal alternate splicing or mutations in the coding region. The relation
      between activity and mRNA levels was studied by short interfering RNA (siRNA)
      method, which showed that in the siRNA treated cells the down-regulation of dCK
      expression, and activity followed each other. However, in control cells the mRNA
      levels remained stable but the protein activity markedly decreased. These data
      demonstrate that the dCK activity is not reflected by dCK mRNA expression that
      indicates a post-translational mechanism(s).

PMID- 16436272
TI  - Selective lysis of erythrocytes infected with the trophozoite stage of Plasmodium
      falciparum by polyene macrolide antibiotics.
AB  - The continuous increase in strains of the human malaria parasite Plasmodium
      falciparum resistant to most front-line antimalarial compounds is reason for
      grave clinical concern. The search for new drugs led us to investigate a number
      of membrane active polyene macrolide antibiotics, such as amphotericin B,
      nystatin, filipin and natamycin. The interaction of these compounds with sterols
      in bilayer cell membranes can lead to cell damage and ultimately cell lysis. The
      malaria parasite modifies the host erythrocyte membrane by changing the protein
      and lipid composition and thus the infected cell could be a selective target for
      membrane active compounds. We found that erythrocytes infected with the
      trophozoite stage of P. falciparum were particularly susceptible to lysis by
      amphotericin B (Fungizone) and, to a lesser extent, nystatin, as determined by
      ELISA and various microscopy assays. Liposomal amphotericin B (AmBisome)
      displayed a similar specificity for parasitised erythrocytes, but complete lysis
      required a longer incubation period. In contrast, filipin and natamycin did not
      distinguish between normal and parasite-infected erythrocytes, but lysed both at
      similar concentrations. In addition, when added to ring-stage cultures, the
      amphotericin B preparations and nystatin produced a marked disruption in parasite
      morphology in less than 2 h without an accompanying permeabilisation of the
      infected host cell, suggesting a second plasmodicidal mode of action. The results
      imply that selected polyene macrolide antibiotics or their derivatives could find
      application in the treatment of severe malaria caused by of P. falciparum.

PMID- 16436273
TI  - Antioxidative function and biodistribution of [Gd@C82(OH)22]n nanoparticles in
      tumor-bearing mice.
AB  - Oxidative stress is considered to be one of the important mechanisms involved in
      carcinogenesis. In our previous study, gadolinium endohedral metallofullerenol
      ([Gd@C82(OH)22]n nanoparticles) have shown high inhibitory activity on hepatoma
      cell (H22) growth in mice. To explore the antioxidative functions of
      nanoparticles, we investigated the biodistribution of [Gd@C82(OH)22]n
      nanoparticles, the changes of blood coagulation profiles, the metabolism of
      reactive oxygen species (ROS) in the tumor-bearing mice as well as the possible
      relationships between nanoparticles treatment and ROS production in this paper.
      The activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH
      Px), glutathione S-transferase (GST) and catalase (CAT) as well as the levels of
      reduced glutathione (GSH), protein-bound thiols and malondialdehyde (MDA) were
      compared between the tumor-bearing mice and normal mice. Transplanted tumors were
      grown in mice by subcutaneous injection of murine hepatoma cells in the mice. The
      comparison of the above parameters between nanoparticles and cyclophosphamide
      (CTX) therapy were also investigated. [Gd@C82(OH)22]n administration can
      efficiently restore the damaged liver and kidney of the tumor-bearing mice. All
      the activities of enzymes and other parameters related to oxidative stress were
      reduced after [Gd@C82(OH)22]n treatment and tended closely to the normal levels.
      The results suggest that [Gd@C82(OH)22]n nanoparticle treatment could regulate
      ROS production in vivo.

PMID- 16436274
TI  - Estimation of benchmark dose as the threshold levels of urinary cadmium, based on
      excretion of total protein, beta2-microglobulin, and N-acetyl-beta-D
      glucosaminidase in cadmium nonpolluted regions in Japan.
AB  - Previously, we investigated the association between urinary cadmium (Cd)
      concentration and indicators of renal dysfunction, including total protein, beta2
      microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG). In 2778
      inhabitants 50 years of age (1114 men, 1664 women) in three different Cd
      nonpolluted areas in Japan, we showed that a dose-response relationship existed
      between renal effects and Cd exposure in the general environment without any
      known Cd pollution. However, we could not estimate the threshold levels of
      urinary Cd at that time. In the present study, we estimated the threshold levels
      of urinary Cd as the benchmark dose low (BMDL) using the benchmark dose (BMD)
      approach. Urinary Cd excretion was divided into 10 categories, and an abnormality
      rate was calculated for each. Cut-off values for urinary substances were defined
      as corresponding to the 84% and 95% upper limit values of the target population
      who have not smoked. Then we calculated the BMD and BMDL using a log-logistic
      model. The values of BMD and BMDL for all urinary substances could be calculated.
      The BMDL for the 84% cut-off value of beta2-MG, setting an abnormal value at 5%,
      was 2.4 microg/g creatinine (cr) in men and 3.3 microg/g cr in women. In
      conclusion, the present study demonstrated that the threshold level of urinary Cd
      could be estimated in people living in the general environment without any known
      Cd-pollution in Japan, and the value was inferred to be almost the same as that
      in Belgium, Sweden, and China.

PMID- 16436275
TI  - Corticosteroids: the drugs to beat.
AB  - Corticosteroids are the most effective anti-inflammatory therapy for asthma and
      other chronic inflammatory and immune diseases. Recently new insights have been
      gained into the molecular mechanisms whereby corticosteroids suppress
      inflammation. Inflammation is characterised by the increased expression of
      multiple inflammatory genes that are regulated by proinflammatory transcription
      factors, such as nuclear factor-kappaB and activator protein-1. These
      transcription factors bind to and activate coactivator molecules, which acetylate
      core histones and switch on gene transcription. Corticosteroids suppress the
      multiple inflammatory genes that are activated in asthmatic airways mainly by
      reversing histone acetylation of activated inflammatory genes through binding of
      glucocorticoid receptors to coactivators and recruitment of histone deacetylase-2
      (HDAC2) to the activated inflammatory gene transcription complex. Activated
      glucocorticoid receptors also bind to recognition sites in the promoters of
      certain genes to activate their transcription, resulting in secretion of anti
      inflammatory proteins, such as mitogen-activated protein kinase phosphatase,
      which inhibits MAP kinase signalling pathways. Glucocorticoid receptors may also
      interact with other recognition sites to inhibit transcription, for example of
      several genes linked to their side effects. In some patients with steroid
      resistant asthma there are abnormalities in GR signalling pathways. In chronic
      obstructive pulmonary disease (COPD) patients and asthmatic patients who smoke
      HDAC2 is markedly impaired as a result of oxidative and nitrative stress so that
      inflammation is resistant to the anti-inflammatory effects of corticosteroids.
      Corticosteroids are likely to remain the mainstay of asthma therapy and new
      therapeutic strategies may reverse the corticosteroid insensitivity in COPD and
      severe asthma.

PMID- 16436276
TI  - Protection of endothelial-derived vasorelaxation with cariporide, a sodium-proton
      exchanger inhibitor, after prolonged hypoxia and hypoxia-reoxygenation: effect of
      age.
AB  - Calcium overload during hypoxia and reoxygenation exerts deleterious effects in
      endothelial and smooth muscle cells but potential effects of sodium-proton
      exchanger (NHE) inhibitors have never been investigated in both adult and
      senescent vessels. Isolated aortic rings from adult and senescent rats were
      submitted to hypoxia (50 min) or to hypoxia/reoxygenation (20/30 min) without or
      with cariporide (10(-6) M) and aortic vasoreactivity was recorded. After hypoxia,
      relaxation to acetylcholine was preserved in adult rings treated with cariporide
      (-22.3% vs. -9.3% of baseline value in control and treated groups respectively,
      P<0.05) but not in senescents. Cariporide treatment restored relaxation to
      acetylcholine after hypoxia-reoxygenation in adult rings (-32.04% vs. -0.03% of
      baseline value in control and treated groups respectively, P<0.01) and to a
      lesser extent, in senescent rings (-30.8% vs. -24.4% of baseline value in control
      and treated groups respectively, P<0.01). These results suggested that hypoxia
      induced lower acidosis and/or involved other mechanisms of proton extrusion than
      NHE in senescent aorta. Improvement of endothelial function with cariporide after
      reoxygenation in senescent aorta, but in a lesser extent than in adult aorta,
      suggests a lower role of NHE in pH regulation and subsequent calcium overload
      during aging.

PMID- 16436277
TI  - Toll-like receptors--novel targets in allergic airway disease (probiotics,
      friends and relatives).
AB  - Experimental and epidemiological studies enabled to hypothesize that stimulation
      of the immune system by selected microbial products may prevent or treat allergic
      diseases. According to recent advances in molecular immunology, this stimulation
      acts via group of conserved receptors present on antigen presenting cells, known
      as toll-like receptors (TLRs). These receptors play an essential role in antigen
      presentation and latter development of immune response into pro-allergic (Th2),
      cellular (Th1) or regulatory (Tr1) responses. Since toll-like receptors govern
      decisive points in immune regulation, an extensive research focuses on agents
      interfering with their immunomodulatory activities. In this report, we review
      information on the potential use of microbial products in allergy prevention and
      therapy, which are believed to target toll-like receptor network. Current toll
      like receptor-based approaches, as well as potential use of lipopolysaccharide
      (and derivates), oligonucleotides, mycobacteria, bacterial extracts, and
      probiotics are discussed herein.

PMID- 16436278
TI  - Challenges nurses face in coping with the HIV/AIDS pandemic in Africa.

PMID- 16436279
TI  - Comparison of three multiplex cytokine analysis systems: Luminex, SearchLight and
      FAST Quant.
AB  - Multiplex cytokine analysis technologies have become readily available in the
      last five years. Two main formats exist: multiplex sandwich ELISA and bead based
      assays. While these have each been compared to individual ELISAs, there has been
      no direct comparison between the two formats. We report here the comparison of
      two multiplex sandwich ELISA procedures (FAST Quant and SearchLight) and a bead
      based assay (UpState Luminex). All three kits differed from each other for
      different analytes and there was no clear pattern of one system giving
      systematically different results than another for any analyte studied. We suggest
      that each system has merits and several factors including range of analytes
      available, prospect of development of new analytes, dynamic range of the assay,
      sensitivity of the assay, cost of equipment, cost of consumables, ease of use and
      ease of data analysis need to be considered when choosing a system for use. We
      also suggest that results obtained from different systems cannot be combined.

PMID- 16436280
TI  - The development of species-specific immunodiagnostics for Stachybotrys chartarum:
      the role of cross-reactivity.
AB  - Mold contamination and exposure to fungi in indoor environments has been
      associated with various adverse health effects but little is known about the
      significance of individual fungal species in the initiation or exacerbation of
      such effects. Using Stachybotrys chartarum as a model fungus we sought to
      demonstrate that monoclonal antibodies (mAbs) can provide species-specific
      diagnostic reagents and also be used to investigate immunological cross
      reactivity patterns among fungi. Mice were immunized with S. chartarum spore
      walls and monoclonal antibodies were screened against 60 fungal species and 24
      different isolates of S. chartarum using an indirect ELISA. One species-specific
      mAb (IgG(1)) reacted only with spore preparations but not mycelium of S.
      chartarum or propagules of any other fungus. Five cross-reactive mAbs (IgM)
      documented extensive cross-reactivity among nine related Stachybotrys species and
      several non-related genera including several species of Cladosporium,
      Memnoniella, Myrothecium and Trichoderma. We also found that the ELISA reactivity
      for cross-reactive antigens and different isolates of S. chartarum differed
      considerably for normalized total amounts of mycelial antigen. We demonstrate
      that mAbs and immunoassays have the potential to detect S. chartarum species
      specifically. The observed reactivity patterns with cross-reactive mAbs suggest
      that several fungi may share common antigens and that the majority of antigens
      are expressed by spores and mycelia. The observed cross-reactivity patterns need
      to be considered for accurate interpretations of environmental and serological
      analyses.

PMID- 16436281
TI  - Molecular details of Itk activation by prolyl isomerization and phospholigand
      binding: the NMR structure of the Itk SH2 domain bound to a phosphopeptide.
AB  - The Src homology 2 (SH2) domain of interleukin-2 tyrosine kinase (Itk) is a
      critical component of the regulatory apparatus controlling the activity of this
      immunologically important enzyme. To gain insight into the structural features
      associated with the activated form of Itk, we have solved the NMR structure of
      the SH2 domain bound to a phosphotyrosine-containing peptide (pY) and analyzed
      changes in trans-hydrogen bond scalar couplings ((3h)J(NC')) that result from pY
      binding. Isomerization of a single prolyl imide bond in this domain is
      responsible for simultaneous existence of two distinct SH2 conformers. Prolyl
      isomerization directs ligand recognition: the trans conformer preferentially
      binds pY. The structure of the SH2/pY complex provides insight into the ligand
      specificity; the BG loop in the ligand-free trans SH2 conformer is pre-arranged
      for optimal contacts with the pY+3 residue of the ligand. Analysis of (3h)J(NC')
      couplings arising from hydrogen bonds has revealed propagation of structural
      changes from the pY binding pocket to the CD loop containing conformationally
      heterogeneous proline as well as to the alphaB helix, on the opposite site of the
      domain. These findings offer a structural framework for understanding the roles
      of prolyl isomerization and pY binding in Itk regulation.

PMID- 16436282
TI  - Solution conformation and heparin-induced dimerization of the full-length
      extracellular domain of the human amyloid precursor protein.
AB  - Proteolytic cleavage of the amyloid precursor protein (APP) by beta and gamma
      secretases gives rise to the beta-amyloid peptide, considered to be a causal
      factor in Alzheimer's disease. Conversely, the soluble extracellular domain of
      APP (sAPPalpha), released upon its cleavage by alpha-secretase, plays a number of
      important physiological functions. Several APP fragments have been structurally
      characterized at atomic resolution, but the structures of intact APP and of full
      length sAPPalpha have not been determined. Here, ab initio reconstruction of
      molecular models from high-resolution solution X-ray scattering (SAXS) data for
      the two main isoforms of sAPPalpha (sAPPalpha(695) and sAPPalpha(770)) provided
      models of sufficiently high resolution to identify distinct structural domains of
      APP. The fragments for which structures are known at atomic resolution were
      fitted within the solution models of full-length sAPPalpha, allowing localization
      of important functional sites (i.e. glycosylation, protease inhibitory and
      heparin-binding sites). Furthermore, combined results from SAXS, analytical
      ultracentrifugation (AUC) and size-exclusion chromatography (SEC) analysis
      indicate that both sAPPalpha isoforms are monomeric in solution. On the other
      hand, SEC, bis-ANS fluorescence, AUC and SAXS measurements showed that sAPPalpha
      forms a 2:1 complex with heparin. A conformational model for the
      sAPPalpha:heparin complex was also derived from the SAXS data. Possible
      implications of such complex formation for the physiological dimerization of APP
      and biological signaling are discussed in terms of the structural models
      proposed.

PMID- 16436283
TI  - Exercise training exacerbates tourniquet ischemia-induced decreases in GLUT4
      expression and muscle atrophy in rats.
AB  - The current study determined the interactive effects of ischemia and exercise
      training on glycogen storage and GLUT4 expression in skeletal muscle. For the
      first experiment, an acute 1-h tourniquet ischemia was applied to one hindlimb of
      both the 1-week exercise-trained and untrained rats. The contralateral hindlimb
      served as control. For the second experiment, 1-h ischemia was applied daily for
      1 week to both trained (5 h post-exercise) and untrained rats. GLUT4 mRNA was not
      affected by acute ischemia, but exercise training lowered GLUT4 mRNA in the acute
      ischemic muscle. GLUT4 protein levels were elevated by exercise training, but not
      in the acute ischemic muscle. Exercise training elevated muscle glycogen above
      untrained levels, but this increase was reversed by chronic ischemia. GLUT4 mRNA
      and protein levels were dramatically reduced by chronic ischemia, regardless of
      whether the animals were exercise-trained or not. Chronic ischemia significantly
      reduced plantaris muscle mass, with a greater decrease found in the exercise
      trained rats. In conclusion, the exercise training effect on muscle GLUT4 protein
      expression was prevented by acute ischemia. Furthermore, chronic ischemia-induced
      muscle atrophy was exacerbated by exercise training. This result implicates that
      exercise training could be detrimental to skeletal muscle with severely impaired
      microcirculation.

PMID- 16436284
TI  - Herbal monoterpene alcohols inhibit propofol metabolism and prolong anesthesia
      time.
AB  - 2,6-Diisopropylphenol (Propofol) is a short-acting intravenous anesthetic that is
      rapidly metabolized by glucuronidation and ring hydroxylation catalyzed by
      cytochrome P450. The goal of this research was to determine whether dietary
      monoterpene alcohols (MAs) could be used to prolong the anesthetic effect of
      propofol by inhibiting propofol metabolism in animals. Mice were injected
      intraperitoneally (i.p.) with MAs (100-200) mg/kg followed by the administration
      of 100 mg/kg propofol 40 min later via an i.p. injection. The time of the
      anesthesia of each mouse was recorded. It was found that (+/-)-borneol, (-)
      carveol, trans-sobrerol, and menthol significantly extended the anesthetic effect
      of propofol (>3 times). The concentration of propofol in the mouse blood over
      time (up to 180 min) also increased in mice pre-treated with (-)-borneol, (-)
      carveol, and trans-sobrerol. The volume of distribution of propofol decreased in
      the (-)-borneol (p<0.05), pre-treated group as compared to the propofol control
      group. Moreover, the maximum blood concentration of propofol and the
      concentration of propofol in the blood as indicated by the area under the curve
      were significantly increased in (-)-borneol and (-)-carveol pre-treated groups.
      Additional evidence using rat hepatocytes showed that (-)-borneol inhibited
      propofol glucuronidation whereas trans-sobrerol and (-)-carveol inhibited
      cytochrome P450 dependent microsomal aminopyrine N-demethylation. These results
      suggest that (-)-borneol extends propofol-induced anesthesia by inhibiting its
      glucuronidation in the mouse whereas trans-sobrerol (-)-carveol extends propofol
      induced anesthesia by inhibiting P450 catalyzed propofol metabolism.

PMID- 16436286
TI  - Implicit cognition is impaired and dissociable in a head-injured group with
      executive deficits.
AB  - Implicit or non-conscious cognition is traditionally assumed to be robust to
      pathology but Gomez-Beldarrain et al. recently showed deficits on a single
      implicit task after head injury. Laboratory research suggests that implicit
      processes dissociate. This study therefore examined implicit cognition in 20 head
      injured patients and age- and IQ-matched controls using a battery of four
      implicit cognition tasks: a serial reaction time task (SRT), mere exposure effect
      task, automatic stereotype activation and hidden co-variation detection. Patients
      were assessed on an extensive neuropsychological battery, and MRI scanned.
      Inclusion criteria included impairment on at least one measure of executive
      function. The patient group was impaired relative to the control group on all the
      implicit cognition tasks except automatic stereotype activation. Effect size
      analyses using the control mean and standard deviation for reference showed
      further dissociations across patients and across implicit tasks. Patients
      impaired on implicit tasks had more cognitive deficits overall than those
      unimpaired, and a larger dysexecutive self/other discrepancy (DEX) score
      suggesting greater behavioural problems. Performance on the SRT task correlated
      with a composite measure of executive function. Head injury thus produced
      heterogeneous impairments in the implicit acquisition of new information.
      Implicit activation of existing knowledge structures appeared intact. Impairments
      in implicit cognition and executive function may interact to produce
      dysfunctional behaviour after head injury. Future comparisons of implicit and
      explicit cognition should use several measures of each function, to ensure that
      they measure the latent variable of interest.

PMID- 16436285
TI  - Plasma leptin response to oral glucose tolerance and fasting/re-feeding tests in
      rats with fructose-induced metabolic derangements.
AB  - The aim of this study was to compare the postprandial leptin response in rats
      with and without metabolic syndrome induced by a fructose-enriched diet. The
      effect of aging and the association between variations in metabolic substrates
      was also evaluated. Oral glucose tolerance test (OGTT) and fasting/re-feeding
      test were used to evaluate the responses of leptin and to explore the dynamic
      relationship between endogenous leptin and metabolic substrates, including
      glucose, insulin and triglycerides (TG). At the 7th week, plasma leptin was
      unchanged in control rats after oral glucose loading. However, plasma leptin
      levels increased in fructose-fed rats with insulin resistant OGTT curves. At the
      11th month, plasma leptin level was reduced during starvation and returned to the
      level prior to starvation during re-feeding in control rats. In contrast, the
      starvation-induced reduction in leptin showed a potentially larger rebound effect
      during re-feeding in fructose-fed rats. Analysis of covariance demonstrated that
      there alone was no interactive effect of dietary manipulation between leptin and
      TG, suggesting that fructose diet-induced insulin resistance-related metabolic
      syndrome may concomitantly elevate leptin and TG. Furthermore, multiple
      regression analysis suggests TG was the primary correlative determinant of
      endogenous leptin concentration. Our data showed that there are different
      patterns of leptin response to OGTT and fasting/re-feeding tests in rats with and
      without metabolic syndrome. The results suggest that these effects may be related
      to a TG-mediated impairment of leptin function and a protective mechanism to
      reduce lipid-induced tissue damage in patients with metabolic syndrome.

PMID- 16436287
TI  - Artesunate plus sulfadoxine-pyrimethamine in the treatment of uncomplicated
      Plasmodium falciparum malaria during pregnancy in eastern Sudan.
AB  - Malaria during pregnancy is associated with serious adverse effects; these could
      be avoided with effective treatment. Artesunate plus sulfadoxine-pyrimethamine
      (AS+SP) is a promising antimalarial combination; however, few data are available
      on its safety during pregnancy. The present study was carried out in New Halfa
      Hospital, eastern Sudan, between September 2004 and March 2005. Thirty-two
      pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria were
      treated with AS+SP at a mean of 29.7 weeks of gestation. The patients were
      followed-up until delivery and the babies were followed-up until the age of 1
      month. The drug was well tolerated, the parasitaemia was cleared and the patients
      were symptom-free within 2 days. All the patients delivered full-term live
      babies. One of the babies died on the fourth day; none of the women died and
      there was no miscarriage, stillbirth, or congenital abnormalities in the newborn
      babies. Thus, this small descriptive study failed to detect unintended effects of
      AS+SP during pregnancy.

PMID- 16436288
TI  - The metabolism of cholesterol and certain hormonal steroids by Treponema
      denticola.
AB  - The aim was to investigate whether reference cultures and fresh isolates of
      Treponema denticola are able to 5alpha-reduce and further metabolise
      testosterone, 4-androstenedione, progesterone, corticosterone, cortisol or
      cholesterol. Two reference and five freshly isolated cultures of T. denticola
      were incubated with either radiolabeled or unlabeled steroid substrates; in the
      first case products were identified by thin layer chromatography and in the
      latter by gas chromatography-mass spectroscopy. All the substrates were 5alpha
      reduced. Both reference cultures and fresh isolates of T. denticola presented
      3beta- and 17beta-hydroxy steroid dehydrogenase activity. It was concluded that
      T. denticola was capable of steroid metabolism and hypotheses are discussed
      regarding the in vivo function of this metabolism including, T. denticola
      utilising host supplied steroids as growth factors and T. denticola steroid
      metabolism acting as a virulence factor.

PMID- 16436289
TI  - Biofilm growth and characteristics in an alternating pumped sequencing batch
      biofilm reactor (APSBBR).
AB  - A novel biofilm reactor-alternating pumped sequencing batch biofilm reactor
      (APSBBR)-was developed to treat synthetic dairy wastewater at a volumetric
      chemical oxygen demand (COD) loading rate of 487 g COD m(-3) d(-1) and an areal
      loading rate of 5.4 g COD m(-2) d(-1). This biofilm reactor comprised two tanks,
      Tanks 1 and 2, with two identical plastic biofilm modules in each tank. The
      maximum volume of bulk fluid in the two-tank reactor was the volume of one tank.
      The APSBBR was operated as a sequencing batch biofilm reactor with five
      operational phases-fill (25 min), anoxic (9 h), aerobic (9 h), settle (6 h) and
      draw (5 min). The fill, anoxic, settle and draw phases occurred in Tank 1. In the
      aerobic phase, the wastewater was circulated between the two tanks with
      centrifugal pumps and aeration was mainly achieved through oxygen absorption by
      micro-organisms in the biofilms when they were exposed to the air. In this paper,
      the biofilm growth and characteristics in the APSBBR were studied in a 98-day
      laboratory-scale experiment. During the course of the study, it was found that
      the biofilm thickness (delta) in Tank 1 ranged from 1.2 to 7.2 mm and that in
      Tank 2 from 0.5 to 2.2 mm; the biofilm growth against time (t) can be simulated
      as delta=0.07t0.99 (R2 = 0.97, P = 0.002) in Tank 1 and delta = 0.08t0.66 (R2 =
      0.81, P = 0.04) in Tank 2. The biomass yield coefficient, Y, was 0.18 g volatile
      solids (VS) g(-1) COD removal. The biofilm density in both tanks, X, decreased as
      the biofilm thickness increased and can be correlated to the biofilm thickness,
      delta .

PMID- 16436290
TI  - Effect of reeds and feeding operations on hydraulic behaviour of vertical flow
      constructed wetlands under hydraulic overloads.
AB  - Vertical flow constructed wetlands (VFCWs) have been very successful in France
      over the last 5 years. The sizing of VFCWs is still roughly based on organic load
      acceptance with slight clear water intrusion into the sewerage system which is
      often wrong in the context of small communities. To specify the hydraulic limits
      would be of great help to Water Authorities in deciding at what point is it
      preferable to build separate sewers rather than adapt the wastewater treatment
      plant. The study of the hydraulic limits of reed beds, based on the knowledge of
      hydrodynamics in unsaturated porous media, shows the ability of the system to
      accept flow overloads. Measuring different parameters (flow, pollutant removal,
      infiltration rate (IR), pressure head profiles) in pilot and full-scale studies,
      we explain the hydraulic behaviour of the filter, and the role of reeds and batch
      frequency on the IRs. Consequently, new hydraulic limits with accompanying sizing
      rules and operational recommendations according to the level of deposit on the
      filter surface are suggested. The study shows the robustness of reed beds systems
      as designed in France to accept hydraulic overloads. Overloads up to ten times
      the dry weather flow are possible whilst still complying with the European
      standards.

PMID- 16436291
TI  - Evaluation of the catalytic reduction of nitrate for the determination of
      dissolved organic nitrogen in natural waters.
AB  - The catalytic reduction of nitrate ions into nitrogen gas was tested to partly
      remove dissolved inorganic nitrogen (DIN) before the determination of dissolved
      organic nitrogen (DON). Experiments were conducted on nitrate solutions enriched
      with natural organic matter (NOM) isolates previously extracted from surface
      waters. Three catalysts Pd-In/Al2O3, Pd-Sn/Al2O3 and Pd/SnO2 were tested. Their
      noble metal (palladium) and promoter metal (indium or tin) contents are 5 and
      1.75 wt%, respectively. Preliminary experiments performed on a solution
      containing 17 amino acids showed that most compounds were removed by less than
      15%, probably due to sorption onto the catalysts. Reduction of nitrate in absence
      of NOM was complete after 20 min of reaction time and the removal of DIN was
      about 80% (about 19% formation of ammonium). In the presence of NOM (DOC 20
      mgC/L, DON 0.67 mg N/L), the kinetic of nitrate reduction was slower and the
      reduction in DIN content was limited to 15% i.e. selectivity toward ammonium
      reached 85%. Adsorption tests showed a similar removal of both DOC and DON of
      about 70% and 30% onto Pd-Sn/Al2O3 and Pd/SnO2 catalysts, respectively, which
      confirmed that NOM probably compete with nitrate for active catalytic sites. In
      conclusion, catalytic reduction of nitrate before DON determination cannot be
      used because of DON sorption and low DIN removal.

PMID- 16436293
TI  - The use of fortified soil-clay as on-site system for domestic wastewater
      purification.
AB  - The quest for simple, low-cost and high-performance decentralized wastewater
      treatment system for domestic application in developing nations necessitated this
      study. Clay samples collected from different deposits in Nigeria were
      characterized by studying the mineralogical and geochemical composition using X
      ray diffraction (XRD) and atomic absorption spectroscopy (AAS), respectively.
      Three major clay minerals of kaolinite, illite and smectite were identified. The
      geochemical studies showed the abundance of SiO2, Al2O3 and H2O+ in each of the
      clay samples. Performance efficiency studies were conducted to determine the best
      combination ratio of pebbles/soil-clay. Soil-clay fortified by pebbles in
      combination ratios of 1:3 (i.e. pebbles:soil-clay = 1:3 (w/w) showed the optimum
      water purification, while the combination 3:1 gave the least. The flow rate
      studies showed that the wastewater had a longer residence time in non-fortified
      soil-clay than in fortified soil-clay. Two modes of treatment methods were
      employed-single and double column treatment methods (SCT and DCT). The two
      methods gave effluents of good quality characteristics, but those from the DCT
      were of better quality. The quality of effluents also varies from one clay type
      to another. The quality of effluents from media containing smectite clay mineral
      was better than those from other columns. Repeated usage of the fortified clay
      column showed a decrease of pH, TS and DO, and an increase of COD when monitored
      over a period of 10 days.

PMID- 16436292
TI  - Volatile fatty acid impacts on nitrite oxidation and carbon dioxide fixation in
      activated sludge.
AB  - Batch test were performed to assess nitrite removal, nitrate formation, CO2
      fixation, gaseous nitrogen production and microbial density in activated sludge
      exposed to volatile fatty acid (VFA) mixtures. Nitrite removal and nitrate
      formation were both affected by the presence of VFAs, but to different degrees.
      Nitrate formation rates were reduced to a greater extent (79%) than nitrite
      removal rates (36%) resulting in an apparent unbalanced nitrite oxidation
      reaction. Since the total bacterial density and the nitrite oxidizing bacteria
      (NOB, Nitrospira) concentration remained essentially constant under all test
      conditions, the reduction in rates was not due to heterotrophic uptake of
      nitrogen or to a decrease in the NOB population. In contrast to the nitrogen
      results, VFAs were not found to impact CO2 fixation efficiency. It appeared that
      nitrite oxidation occurred when VFAs were present since the oxidation of nitrite
      provides energy for CO2 fixation. However, nitrate produced from the oxidation of
      nitrite was reduced to gaseous nitrogen products. N2O gas was detected in the
      presence of VFAs which was a clear indication that VFAs stimulated an alternative
      pathway, such as aerobic denitrification, during biotransformation of nitrogen in
      activated sludge.

PMID- 16436294
TI  - The modulation of gene expression in osteoblasts by thrombin coated on biphasic
      calcium phosphate ceramic.
AB  - For many years, fibrin sealants were associated with bone substitutes to promote
      bone healing. However, the osteoblastic response to fibrin sealant components
      remains poorly documented. In this study, MC3T3-E1 osteoblastic cells were
      cultured on biphasic calcium phosphate ceramic (MBCP) coated with Tissucol
      components (thrombin and fibrinogen). Analysis of osteoblastic differentiation
      markers by RT-PCR revealed that MBCP coated with Tissucol stimulated mRNA levels
      for osteocalcin and alkaline phosphatase (ALP). Of all the components of
      Tissucol, thrombin has been reported to affect osteoblastic behavior. Our results
      demonstrated that low thrombin concentrations (0.5-5 U/ml) stimulated mRNA levels
      for ALP, whereas high thrombin concentrations (50-100 U/ml) decreased mRNA levels
      for ALP and PTH/PTHrP receptor and also increased mRNA level for the
      osteoclastogenesis inhibitor OPG. As thrombin stimulated angiogenesis, we then
      wondered whether thrombin could influence the expression of angiogenic factors.
      Low thrombin concentrations were shown to up-regulate mRNA levels for VEGF-B and
      VEGF-R1, suggesting an autocrine/paracrine role for VEGF-B. Higher thrombin
      concentrations also up-regulated mRNA for VEGF-A and neuropilin-1. In conclusion,
      the association of MBCP with thrombin and fibrinogen appears to be a convenient
      scaffold for bone cell differentiation. Thrombin could also acts at the cellular
      level by increasing the angiogenic potential of osteoblasts as well as their
      responsiveness to thrombin and VEGF.

PMID- 16436295
TI  - Radon mitigation in domestic properties and its health implications--a comparison
      between during-construction and post-construction radon reduction.
AB  - Although United Kingdom (UK) Building Regulations applicable to houses
      constructed since 1992 in Radon Affected Areas address the health issues arising
      from the presence of radon in domestic properties and specify the installation of
      radon-mitigation measures during construction, no legislative requirement
      currently exists for monitoring the effectiveness of such remediation once
      construction is completed and the houses are occupied. To assess the relative
      effectiveness of During-Construction radon reduction and Post-Construction
      remediation, radon concentration data from houses constructed before and after
      1992 in Northamptonshire, UK, a designated Radon Affected Area, was analysed.
      Post-Construction remediation of 73 pre-1992 houses using conventional fan
      assisted sump technology proved to be extremely effective, with radon
      concentrations reduced to the Action Level, or below, in all cases. Of 64 houses
      constructed since 1992 in a well-defined geographical area, and known to have had
      radon-barrier membranes installed during construction, 11% exhibited radon
      concentrations in excess of the Action Level. This compares with the estimated
      average for all houses in the same area of 17%, suggesting that, in some 60% of
      the houses surveyed, installation of a membrane has not resulted in reduction of
      mean annual radon concentrations to below the Action Level. Detailed comparison
      of the two data sets reveals marked differences in the degree of mitigation
      achieved by remediation. There is therefore an ongoing need for research to
      resolve definitively the issue of radon mitigation and to define truly effective
      anti-radon measures, readily installed in domestic properties at the time of
      construction. It is therefore recommended that mandatory testing be introduced
      for all new houses in Radon Affected Areas.

PMID- 16436296
TI  - Treatment of acute postoperative endophthalmitis without hospital admission: do
      we dare?
AB  - INTRODUCTION: We report the successful management of a culture positive case of
      APE, without the need for hospital admission and discuss the merits of this
      strategy. CASE: A 79-year-old lady underwent uncomplicated cataract surgery in
      her left eye using phacoemulsification under topical and intracameral
      anaesthesia. She reported to eye casualty four days later, with pain and vision
      reduced to 6/60 in the left eye. A diagnosis of acute postoperative
      endophthalmitis was made. A vitreous biopsy was performed and antibiotics
      injected intravitreally on the same day. The patient was discharged on oral and
      topical antibiotics on the same day and reviewed subsequently in the clinic as an
      outpatient. Vision steadily improved and at one month following intravitreal
      injection her vision had improved to 6/9 unaided. The cornea remained clear, with
      a quiet anterior chamber and a clear view of the fundus. DISCUSSION: Current
      management of acute postoperative endophthalmitis in the UK includes a vitreous
      biopsy, administration of antibiotics into the vitreous cavity, admission of
      patients to a hospital ward and daily review. It is our opinion that under the
      circumstances where patients are fit and well, without significant co-morbidity,
      hospital admission is not necessary as demonstrated by the patient in our report.

PMID- 16436297
TI  - Analysis of microbial etiology and mortality in patients with brain abscess.
AB  - OBJECTIVES: Despite the technological advancements in diagnostic and
      neurosurgical procedures, brain abscess continues to remain a potentially fatal
      central nervous system infection. In a prospective study we determined the
      predisposing factors and the microbiological profile of brain abscess. We also
      analyzed the mortality in patients with the type of infections identified.
      METHODS: Over a period of 8 years (1997-2004), aspirated pus from 118 patients
      with brain abscess was directly inoculated into BACTEC PLUS+ aerobic and BACTEC
      PLUS+ anaerobic media immediately after collection and subcultured on solid media
      as appropriate. Predisposing factors, if any, were recorded in all patients.
      Mortality of patients during hospital stay was correlated with the type of
      infections identified. RESULTS: Predisposing factors were identified in 94
      (79.7%) patients, otogenic infection being the most common (37/118; 31.4%).
      Microorganisms were demonstrated in 96 (81.4%) patients, by culture in 89 (75.4%)
      patients and by Gram stain in 7 (5.9%) additional cases. A total of 105 organisms
      were isolated - 67 (63.8%) aerobes, 32 (30.5%) anaerobes, 5 (4.8%) mycobacteria
      and 1 (0.9%) fungus. Viridans streptococci (23.8%), Staphylococcus aureus
      (14.3%), Bacteroides fragilis group/species and Peptostreptococcus species (10.5%
      each) were the common isolates. Overall mortality was 14.4%; patients with Gram
      negative infections had higher mortality than Gram-positive infections (6/20; 30%
      vs. 6/63; 9.5%; P=0.02). CONCLUSIONS: Culture of pus immediately after aspiration
      in an automated system yields good results. Gram stain coupled with culture can
      guide the neurosurgeons better to treat their patients more rationally. Patients
      with Gram-negative infections need special attention in terms of management
      because of high mortality rate.

PMID- 16436299
TI  - Festschrift honoring Paula Clayton.

PMID- 16436298
TI  - Current-source density estimation based on inversion of electrostatic forward
      solution: effects of finite extent of neuronal activity and conductivity
      discontinuities.
AB  - A new method for estimation of current-source density (CSD) from local field
      potentials is presented. This inverse CSD (iCSD) method is based on explicit
      inversion of the electrostatic forward solution and can be applied to data from
      multielectrode arrays with various geometries. Here, the method is applied to
      linear-array (laminar) electrode data. Three iCSD methods are considered: the CSD
      is assumed to have cylindrical symmetry and be (i) localized in infinitely thin
      discs, (ii) step-wise constant or (iii) continuous and smoothly varying (using
      cubic splines) in the vertical direction. For spatially confined CSD
      distributions the standard CSD method, involving a discrete double derivative, is
      seen in model calculations to give significant estimation errors when the lateral
      source dimension is comparable to the size of a cortical column (less than
      approximately 1 mm). Further, discontinuities in the extracellular conductivity
      are seen to potentially give sizable errors for even wider source distributions.
      The iCSD methods are seen to give excellent estimates when the correct lateral
      source dimension and spatial distribution of conductivity are incorporated. To
      illustrate the application to real data, iCSD estimates of stimulus-evoked
      responses measured with laminar electrodes in the rat somatosensory (barrel)
      cortex are compared to estimates from the standard CSD method.

PMID- 16436300
TI  - Bulimia nervosa in atypical depression: the mediating role of cyclothymic
      temperament.
AB  - OBJECTIVE: Recent data indicate significant clinical, biological, and treatment
      response overlap between eating and bipolar disorders, especially when soft
      symptoms of either spectrum disorders are considered. The aim of the present
      analyses is to evaluate the lifetime prevalence of bulimia nervosa (BN) in
      patients with atypical depression (AD) and to delineate any demographic,
      clinical, personality or temperamental factors that may characterize this
      subgroup. METHOD: We examined in a semi-structured format 107 consecutive
      patients who met DSM-IV criteria for major depressive episode with atypical
      features and we separated them into two groups according to the co-occurring
      criteria for BN. They were further evaluated on the basis of the Atypical
      Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL 90),
      and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified
      form for reverse vegetative features, as well as Axis I and II comorbidity and
      temperamental dispositions. RESULTS: Seventeen (17.8%) percent of AD met the DSM
      IV criteria for Bulimia Nervosa (BN+). These patients, compared with those who
      did not meet criteria for BN (BN-), were indistinguishable on all demographic and
      most psychopathologic and clinical features (including bipolar I and II), but
      were significantly higher in lifetime comorbidity for Narcissistic, Histrionic,
      Borderline and Dependent personality disorders as well as that for Cyclothymic
      temperament. BN+ also scored higher on the ADDS items of reactivity of mood and
      interpersonal sensitivity. LIMITATIONS: Correlational clinical study in which
      doctors could not be entirely blind to the variables under investigation.
      CONCLUSIONS: Cyclothymic temperament and related mood reactivity and
      interpersonal sensitivity may account for much of the relationship between AD and
      BN. Narcissistic, histrionic and borderline traits, too, seem to be related to
      the presence of a cyclothymic disposition. The data overall, in particular the
      cyclothymic reactivity in the absence of differences in BP-I and II, all support
      the hypothesis that places BN in the "ultra-soft" bipolar realm.

PMID- 16436301
TI  - Depression with above-normal plasma vasopressin: validation by relations with
      family history of depression and mixed anxiety and retardation.
AB  - An anxious-retarded subtype of depression has been derived from the DSM-IV
      category of melancholia. It is defined by combined high scores for anxiety and
      retardation, and is related to family history of depression and increased plasma
      vasopressin (AVP) levels. Central problems concerning this hypothesized
      subcategory are whether elevated plasma AVP is related to family history, whether
      it would be better operationalized by a cut-off level for plasma AVP than as
      continuous variable, and whether the anxious-retarded phenotype would be better
      described in terms that account for full variability of mixed anxiety and
      retardation. A previous study suggested that above-normal plasma AVP was a more
      useful endophenotypic parameter than plasma AVP as a continuous variable. To
      answer these and related questions, 81 patients were investigated. Receiver
      Operating Characteristic analyses yielded a cut-off value of 5.56 pg/ml for above
      normal plasma AVP, log-transformed plasma AVP (ln (AVP)) was used as continuous
      variable, and the correlation between anxiety and retardation was used to account
      for full variability of the anxious-retarded phenotype. Family history was
      related to above-normal plasma AVP (n = 16) and non-significantly to ln (AVP).
      Depression with above-normal plasma AVP, as well as familial depression with
      above-normal plasma AVP, showed a high correlation between anxiety and
      retardation, and this correlation was significantly higher than that found in the
      depressed patient control groups. The data support the delimitation of a largely
      familial depression with above-normal plasma AVP, vasopressinergic activation of
      the hypothalamus-pituitary-adrenal axis and a variable anxious-retarded
      phenotype.

PMID- 16436302
TI  - Influence of aqueous aluminium on the immune system of the freshwater crayfish
      Pacifasticus leniusculus.
AB  - Little is known of the effects of aluminium (Al) on invertebrate immunity despite
      the ubiquitous nature of the metal and its toxicity to aquatic organisms. Here we
      examine the effect of Al at neutral pH on the immune system of the freshwater
      crayfish Pacifasticus leniusculus. Heat-killed bacteria were injected at
      intervals into the haemolymph of crayfish continuously exposed to a sub-lethal
      concentration (500 microg l(-1)) of Al over 40 days. Circulating haemocyte and
      bacterial numbers were monitored for 16 days post-injection at each time
      interval. In the absence of bacterial challenge, the number of circulating
      haemocytes increased in Al-exposed crayfish compared to unexposed controls.
      Aluminium exposure initially reduced the crayfish's ability to clear bacteria
      from the circulation and decreased the rate of recovery in haemocyte numbers
      following bacterial challenge. These effects on bacterial and haemocyte numbers
      were abolished after prolonged exposure (>10 days) to Al, indicating adaptation
      to the metal. Aqueous Al impairs gill function in P. leniusculus by inducing
      hypersecretion of mucus and we suggest that the decrease in immunocompetence is
      due to haemolymph hypoxia. We conclude that exposure to episodic pulses of
      aqueous Al over the short term (<10 days) increases the risk of infection in the
      crayfish by impairing the ability of haemocytes to recognise and/or remove
      bacteria from the circulation.

PMID- 16436303
TI  - Another side of genomics: synthetic biology as a means for the exploitation of
      whole-genome sequence information.
AB  - The successful completion of the Human Genome Project and other sequencing
      projects opened the door for another quantum jump in science advancement. The
      most important public sequence databases are doubling in size every 18 months. By
      revealing the genetic program of many organisms, these efforts endow biologists
      with the ability to study the basic information of life in toto as an initial
      step toward a comprehensive understanding of the complexity of entire organisms.
      We review the area of synthetic biology, defined as the making and use of
      biosystems founded on the chemical synthesis of the coding DNA (and potentially
      RNA). The recent developments discussed here introduce a rich source of
      oligonucleotides to the field: in situ synthesised microarrays, which in fact
      represent nothing else but matrix nucleic acid synthesisers. With this new way of
      producing the oligonucleotides used in the making of synthetic genes in a very
      cost-effective manner, the field of synthetic biology can be expected to change
      dramatically in the next decade. Synthetic genes will then be the tools of choice
      to obtain any sequence at any time in any laboratory.

PMID- 16436304
TI  - Molecular characterization of four rice genes encoding ethylene-responsive
      transcriptional factors and their expressions in response to biotic and abiotic
      stress.
AB  - We isolated and identified four rice genes, OsBIERF1 to OsBIERF4 (Oryza sativa
      benzothiadiazole (BTH)-induced ethylene responsive transcriptional factors (ERF))
      and analyzed their expressions in rice disease resistance response and under
      various abiotic stress conditions. The OsBIERF1-4 proteins contain conserved ERF
      domains, but are categorized into different classes of the previously
      characterized ERF proteins based on their structural organizations. OsBIERF3 and
      OsBIERF2 belong to Classes I and II, respectively; while OsBIRERF1 and OsBIERF4
      are members of Class IV. OsBIERF3 could bind specifically to the GCC box sequence
      and was targeted to nucleus when transiently expressed in onion epidermis cells.
      Expression of OsBIERF1, OsBIERF3 and OsBIERF4 was induced by treatments with BTH
      and salicylic acid, chemical inducers capable of inducing disease resistance
      response in rice. In the BTH-treated rice seedlings, expression of OsBIERF1,
      OsBIERF3 and OsBIERF4 was further induced by infection with Magnaporthe grisea,
      the rice blast fungus, as compared with those in water-treated seedlings.
      OsBIERF1 and OsBIERF3 were activated in an incompatible interaction but not in
      compatible interaction between rice and M. grisea. Moreover, OsBIERF1, OsBIERF3
      and OsBIERF4 were also up-regulated by salt, cold, drought and wounding. These
      results suggest that OsBIERF proteins may participate in different signaling
      pathways that mediate disease resistance response and stress responses to abiotic
      factors.

PMID- 16436305
TI  - Studies of the Ndh complex and photosystem II from mesophyll and bundle sheath
      chloroplasts of the C4-type plant Zea mays.
AB  - In C(4) plants, granal mesophyll (MS) chloroplasts contain higher photosystem
      (PS) II and lower PS I activity than agranal bundle sheath (BS) chloroplasts. The
      maize NAD(P)H dehydrogenase or NAD(P)H-plastoquinone oxidoreductase (also named
      Ndh complex) from MS and BS chloroplasts, contains at least 11 subunits (NdhA-K)
      and is homologous to NADH dehydrogenase or Complex I from mitochondria and
      bacteria. The amount of Ndh complex is higher in BS compared with MS
      chloroplasts. However, there is little information about the interdependence of
      the PS II and Ndh complex in chlororespiration and linear and cyclic electron
      transport in C(4) plants. To characterize the expression of the PS II and Ndh
      complex in maize plastids, we used cytochrome b559 (cyt b559) antibodies and Ndh
      immunoglobulins (IgG) to analyze the Ndh complex and PS II in both MS and BS
      chloroplasts from maize leaves by Western blotting and immunolabeling. In Western
      blot experiments, it was found that the amount of cyt b559 (a marker for PS II)
      is 7-8 times higher in MS than BS chloroplasts. Conversely, the NdhH, -J, -K and 
      E content is 2.5-3 times higher in BS than MS chloroplasts. Similar results were
      obtained in immunolabeling experiments using Ndh IgGs and cyt b559 antibodies in
      MS and BS chloroplasts. These data suggest that in BS chloroplasts, ATP could be
      produced mainly by cyclic electron transport around PS I and Ndh complexes.
      Conversely, the linear electron transport in BS chloroplasts via PS II could have
      a lower production of ATP. These results also suggest that the contribution of
      the Ndh complex in the production of ATP in MS chloroplasts is minimal and that
      instead, this complex could have a chlororespiratory role.

PMID- 16436306
TI  - The effect of abiotic stresses on carbohydrate status of olive shoots (Olea
      europaea L.) under in vitro conditions.
AB  - Olive plants produce both sucrose and mannitol as major photosynthetic products.
      Contrary to previously studied celery [Vitova et al., Mannitol utilisation by
      celery (Apium graveolens) plants grown under different conditions in vitro. Plant
      Sci 2002; 163: 907-16], in vitro these carbohydrates were found to be able to
      sustain growth of olive shoots roughly to the same extent at all tested
      concentrations (1-9% w/v). We studied the involvement of the particular
      components of the endogenous carbohydrate spectrum in response to different
      abiotic stresses (osmotic stress, salinity, low temperature) in vitro. Salinity
      (100mM NaCl) caused a decrease of total soluble carbohydrates, while an increase
      was observed during low-temperature treatment (0 and 4 degrees C). Mannitol
      accumulated primarily under salinity (up to 40% of total soluble carbohydrates
      compared to 10-20% in controls). Only a small (two-fold) increase of proline
      content in salinity stressed plants indicates proline does not play a significant
      role in olive stress response. Low temperature led to an increase of the
      raffinose family oligosaccharides (RFO) proportion in total carbohydrates. We
      conclude that olive plants exploit the high diversity of the carbohydrate
      spectrum in specific response to different stresses.

PMID- 16436307
TI  - Hepatitis vaccination among drug users.
AB  - Hepatitis virus infections are traditionally a major health problem among drug
      users (DUs). Several factors may favor the rapid spread of hepatitis infection in
      this category of patients. HBV and HCV are easily transmitted through exposure to
      infected blood and body fluids. DUs often prepare and use drug solutions
      together. Many in the DU community are infected and this provides multiple
      opportunities for transmission to others. Many of these patients with chronic
      hepatitis virus infection are not aware of their infections and this facilitates
      the spread of the diseases. Viral hepatitis is not inevitable for DUs. Although
      multiple factors have prevented the development of vaccines for hepatitis C, both
      hepatitis A and hepatitis B can be prevented by immunization. The purpose of this
      overview is to summarize and discuss the hepatitis vaccination in this
      population.

PMID- 16436308
TI  - Effects of pH, organic acids, and inorganic ions on lead desorption from soils.
AB  - The desorption characteristics of lead in two variable charge soils (one
      developed from Arenaceous rock (RAR) and the other derived from Quaternary red
      earths (REQ)) were studied, and the effects of pH value, organic acid, and
      competitive ions were examined. Desorption of Pb(2+) decreased from nearly 100.0
      to 20.0% within pH 1.0-4.0 in both soils, and then the decrease diminished at pH
      > 4.0. Organic ligands at relatively low concentrations (< or =10(-3) mol L(-1))
      slightly inhibited Pb(2+) desorption, but enhanced Pb(2+) desorption at higher
      concentrations. In this study, citric acid or acetic acid at higher
      concentrations (>10(-3) mol L(-1)) had the greatest improvement of Pb(2+)
      desorption, followed by malic acid; and the smallest was oxalic acid. Desorption
      of the adsorbed Pb(2+) increased greatly with increasing concentrations of added
      Cu(2+) or Zn(2+). Applied Cu(2+) increased Pb(2+) desorption more than Zn(2+) at
      the same loading.

PMID- 16436309
TI  - Ethnic identity, resettlement stress and depressive affect among Southeast Asian
      refugees in Canada.
AB  - Does commitment to an ethnic identity enhance or jeopardize psychological well
      being? Using data from a study of Southeast Asian "Boat People", this study
      examined the mental health effects of ethnic identification as the former
      refugees confronted common resettlement stressors in Canada--unemployment,
      discrimination and lack of fluency in the dominant society language. The study
      team administered a questionnaire to 647 respondents covering ethnic
      identification, demographic and employment information, language fluency,
      experiences with discrimination, and depressive affect. Context helped determine
      the relationship between ethnic identification and depressive affect. When the
      Southeast Asians encountered racial discrimination or unemployment, ethnic
      identity attachment amplified the risk of depressive affect. By contrast, a
      strongly held ethnic identity provided a psychological advantage for individuals
      experiencing difficulties with the dominant language.

PMID- 16436310
TI  - Advocacy coalitions and pharmacy policy in Denmark--solid cores with fuzzy edges.
AB  - This paper presents the results from a qualitative study in which the Advocacy
      Coalition Framework (ACF) was used to analyze deregulation of the distribution of
      medicine in Denmark in October 2001. The study is based on qualitative methods,
      and it examines the policy process between 1996 and 2001. Data sources were
      documents and qualitative interviews. The results show that minor modifications
      of the ACF are needed to make it fully applicable to the case of pharmacy policy,
      especially when the policy process proceeds in a predominantly corporatist state.
      We found that the policy process was framed by two coalitions advocating
      different belief systems. One coalition wanted the pharmacy sector to be
      controlled by the state, the other wanted a full-scale liberalization. Throughout
      the process there was a general shift in policy core beliefs among the actors
      involved--moving from positively disposed towards a market-oriented reform to
      being more negatively disposed towards such a reform. We argue that two factors
      contributed to this. First, as the discussions about a reform became more
      specific, technical matters began to influence the actors. Second, the legitimacy
      of a solution which did not alter the regulation of the pharmacy sector
      radically, was reinforced by institutionalized norms that made politicians take
      onboard pharmacy professionals' concerns.

PMID- 16436311
TI  - Dorsal raphe vs. median raphe serotonergic antagonism. Anatomical, physiological,
      behavioral, neuroendocrinological, neuropharmacological and clinical evidences:
      relevance for neuropharmacological therapy.
AB  - Monoaminergic neurons located in the central nervous system (CNS) are organized
      into complex circuits which include noradrenergic (NA), adrenergic (Ad),
      dopaminergic (DA), serotonergic (5-HT), histaminergic (H), GABA-ergic and
      glutamatergic systems. Most of these circuits are composed of more than one and
      often several types of the above neurons. Such physiologically flexible circuits
      respond appropriately to both external and internal stimuli which, if not
      modulated adequately, can trigger pathophysiologic responses. A great deal of
      research has been devoted to mapping the multiple functions of the CNS circuitry,
      thereby forming the basis for effective neuropharmacological therapeutic
      approaches. Such lineal strategies that seek to normalize complex and mixed
      physiological disorders, however, meet only partial therapeutic success and are
      often followed by undesirable side effects and/or total failure. In light of
      these, we have worked to develop possible models of CNS circuitry that are less
      affected by physiological interaction using the models to design more effective
      therapeutic approaches. In the present review, we cite and present evidence
      supporting the dorsal raphe versus median raphe serotonergic circuitry as one
      model of a reliable paradigm, necessary to the clear understanding and therapy of
      many psychiatric and even non-psychiatric disturbances.

PMID- 16436313
TI  - Degradation and by-product formation of diazinon in water during UV and
      UV/H(2)O(2) treatment.
AB  - Kinetics and degradation products resulting from the application of UV and
      UV/H(2)O(2) to the US EPA Contaminant Candidate List pesticide diazinon were
      studied. Batch experiments were conducted with both monochromatic (low pressure
      [LP] UV 253.7 nm) and polychromatic (medium pressure [MP] UV 200-300 nm) UV
      sources alone or in the presence of up to 50 mg l(-1) H(2)O(2), in a quasi
      collimated beam apparatus. Degradation of diazinon by both UV and UV/H(2)O(2)
      exhibited pseudo first order reaction kinetics, and quantum yield of 8.6 x 10(-2)
      and 5.8 x 10(-2) mol E(-1) for LP and MP lamps respectively. Photolysis studies
      under MP UV lamp showed 2-isopropyl-6-methyl-pyrimidin-4-ol (IMP) to be the main
      degradation product of diazinon at aqueous solution pH values of 4, 7 and 10.
      Trace levels up to 1.8 x 10(-3) microM of diazinon oxygen analogue diethyl 2
      isopropyl-6-methylpyrimidin-4-yl phosphate (diazoxon) were detected only during
      the UV/H(2)O(2) reaction. Decay of both products was observed, as the UV/H(2)O(2)
      reaction prolonged, yet no mineralization was achieved over the UV fluence levels
      examined. Photolysis kinetics, quantum yield and UV/H(2)O(2) degradation of the
      reaction product IMP was determined using MP UV lamp at pH values of 4, 7 and 10.

PMID- 16436312
TI  - Protection of betulin against cadmium-induced apoptosis in hepatoma cells.
AB  - The protective effects of betulin (BT) against cadmium (Cd)-induced cytotoxicity
      have been previously reported. However, the mechanisms responsible for these
      protective effects are unclear. Therefore, this study investigated the mechanisms
      responsible for the protection of BT against Cd-induced cytotoxicity in human
      hepatoma cell lines. The protection of BT against Cd cytotoxicity was more
      effective in the HepG2 than in the Hep3B cells. The protection of BT on Cd
      induced cytotoxicity in the HepG2 cells appeared to be related to the inhibition
      of apoptosis, as determined by PI staining and DNA fragmentation analysis. The
      anti-apoptosis exerted by BT involved the blocking of Cd-induced reactive oxygen
      species (ROS) generation, the abrogation of the Cd-induced Fas upregulation, the
      blocking of caspase-8-dependent Bid activation, and subsequent inhibition of
      mitochondrial pathway. The BT pretreatment did not affect the p21 and p53
      expression levels, when compared with those of the treated cells with Cd alone.
      BT induced the transient S phase arrest at an early stage and the G0/G1 arrest at
      a relatively late stage, but it did not observe the sub-G1 apoptotic peak. In the
      Hep3B cells, Cd did not induce ROS generation. The BT pretreatment partially
      inhibited the Cd-induced apoptosis, which was related with the incomplete
      blockage in caspase-9 or -3 activation, as well as in Bax activation. Taken
      together, it was found that Cd can induce apoptosis via the Fas-dependent and 
      independent apoptosis pathways. However, the observed protective effects of BT
      were clearly more sensitive to Fas-expressing HepG2 cells than to Fas-deficient
      Hep3B cells.

PMID- 16436314
TI  - Low seroprevalence of antibodies to Neospora caninum in wild canids in Israel.
AB  - The role of domestic dogs in the epidemiology of Neospora caninum as well as the
      relationship between N. caninum infection of farm dogs and cattle were
      demonstrated, however, evidence is scarce regarding the role of wild canids in
      domestic animal neosporosis. The present study was undertaken to evaluate the
      role of wild canids in the epidemiology of bovine neosporosis in Israel by
      analyzing the prevalence of antibodies to N. caninum in wild canids. Sera samples
      were collected from 114 free ranging wild golden jackals (Canis aureus), 24 red
      foxes (Vulpes vulpes) and nine wolves (Canis lupus), which were collected in
      Israel during the years 1999-2004. Of a total of 147 wild canids tested
      antibodies to N. caninum were only found in two golden jackals with IFAT titers
      of 1:50, and in one red fox and one wolf with IFAT titer of 1:400. The low
      seroprevalence found in this study (2.7%) indicated that wild canids probably do
      not have an important role in the epidemiology of N. caninum in Israel. However,
      since the diet of different species of wild canids and even diverse populations
      of the same canid species vary, it is possible that other results might be
      obtained from specific wild canids populations, which scavenge in the vicinity of
      infected bovines.

PMID- 16436315
TI  - Prognostic value of trophoblastic proliferation in complete hydatidiform moles in
      predicting persistent disease.
AB  - The clinical outcome of patients with complete hydatidiform moles (CHM) is
      variable. The correlation between trophoblastic proliferation and development of
      persistent disease was evaluated. A hundred and fifty-one cases with the initial
      diagnosis of CHM were re-evaluated histopathologically. The need for chemotherapy
      and occurrence of metastatic disease was correlated with the histologic grade
      using a three-level score. Twelve out of 151 cases were re-evaluated as hydropic
      abortion, partial moles, or were insufficient for morphologic examination,
      representing a diagnostic agreement of 92%. A total of 63.4% of the CHM presented
      with low trophoblastic proliferation with focal areas of slight hyperplasia
      (grade 1), and 23.7% with moderate proliferation with slight anaplasia and medium
      sized sheets of free trophoblast in between the villies (grade 2). In all, 12.9%
      of the cases showed marked hyperplasia with marked anaplasia and involvement of
      nearly all villies, as well as a large amount of intervillous trophoblastic
      sheets (grade 3). Twenty-six of the CHM (19%) required chemotherapy. Grade 3, on
      histology, showed a positive correlation with the necessity of chemotherapy
      (p=0.04), but not with the occurrence of metastatic disease. Histomorphology
      might predict the risk of persistent disease, indicating the necessity for closer
      a follow-up, but further studies are required.

PMID- 16436317
TI  - Fetal and neonatal hydronephrosis.

PMID- 16436316
TI  - Antioxidant activity of Rhizophora mangle bark.
AB  - The antioxidant activity of Rhizophora mangle bark aqueous extract and its
      majoritary component and high molecular weight polyphenols' fraction were studied
      using deoxyribose assay. The total extract and its fraction showed scavenging
      activity of hydroxyl radicals and hability to chelate iron ions.

PMID- 16436318
TI  - Cadmium-induced disturbances in lactating mammary glands of mice.
AB  - Previous studies in various species have demonstrated that cadmium levels in milk
      are low and that cadmium is retained in the mammary glands of lactating rodents.
      The objective of the present study was to examine mammary glands following
      cadmium exposure during peak lactation. Mice were given 5 microg, 100 microg or
      2000 microg cadmium/kg body weight subcutaneously on lactation days 8-10 and
      mammary glands were dissected on lactation day 11 for histology, quantitative
      gene expression and mineral analyses. Cadmium exposure induced morphological
      changes in the lactating mammary gland. A remodelling of the lactating mammary
      tissue including an increase in fat content, a less active feature of the mammary
      alveolar epithelial cells and more condensed appearance of the milk alveoli were
      observed. Although these changes were most prominent in the animals exposed to
      the highest cadmium dose similar morphological alterations were indicated at the
      two lower doses. A significant negative dose-response relationship between beta
      casein gene expression and exposure of cadmium was demonstrated, while mRNA
      levels of alpha-lactalbumin were not affected by cadmium treatment. Furthermore,
      reduced levels of calcium in the mammary glands of the dams exposed to the
      highest cadmium dose and a positive correlation between calcium and beta-casein
      were demonstrated. No other differences were detected among the cadmium dose
      groups in mammary levels of calcium, zinc, iron or copper. In conclusion, our
      results indicate that cadmium disturbs the function of the lactating mammary
      gland, which consequently may impair the development of the suckling offspring.

PMID- 16436319
TI  - Preparation and improvement of release behavior of chitosan microspheres
      containing insulin.
AB  - Chitosan microsphere has potential applications in orally and other mucosally
      administration of protein and peptide drug, because it shows excellent
      mucoadhesive and permeation enhancing effect across the biological surfaces. The
      control of the size and size distribution of chitosan microsphere is necessary in
      order to improve its reproducibility, bioavailability and repeatable release
      behavior. Furthermore, it is a big challenge how to maintain the chemical
      stability of protein drug and improve its release behavior in the preparation of
      chitosan microspheres, because conventional crosslinking method by glutaraldehyde
      cannot be used in encapsulation of protein drug containing amino group. In this
      study, we established a method to prepare uniform-sized microsphere, and solve
      above problems by combining a special membrane emulsification technique and a
      step-wise crosslinking method. The preparative condition was optimized, and the
      chemical stability of protein, encapsulation efficiency, and release behavior
      were compared with conventional preparative method of drug-loaded chitosan
      microspheres. As a result, fairly uniform chitosan microspheres were obtained
      with a coefficient of variation (C.V.) value less than 11%, and the step-wise
      crosslinking method developed specially for membrane emulsification method
      provided the microspheres with higher encapsulation efficiency (80%), higher
      chemical stability of insulin (>95%), lower burst release and steady release
      behavior.

PMID- 16436320
TI  - Quantitative estimation of film forming polymer-plasticizer interactions by the
      Lorentz-Lorenz Law.
AB  - Molar refraction as well as refractive index has many uses. Beyond confirming the
      identity and purity of a compound, determination of molecular structure and
      molecular weight, molar refraction is also used in other estimation schemes, such
      as in critical properties, surface tension, solubility parameter, molecular
      polarizability, dipole moment, etc. In the present study molar refraction values
      of polymer dispersions were determined for the quantitative estimation of film
      forming polymer-plasticizer interactions. Information can be obtained concerning
      the extent of interaction between the polymer and the plasticizer from the
      calculation of molar refraction values of film forming polymer dispersions
      containing plasticizer.

PMID- 16436321
TI  - Design and evaluation of a dry coated drug delivery system with an impermeable
      cup, swellable top layer and pulsatile release.
AB  - In this investigation a novel oral pulsatile drug delivery system based on a core
      in-cup dry coated tablet, where the core tablet surrounded on the bottom and
      circumference wall with inactive material, is proposed. The system consists of
      three different parts, a core tablet, containing the active ingredient, an
      impermeable outer shell and a top cover layer-barrier of a soluble polymer. The
      core contained either diclofenac sodium or ketoprofen as model drugs. The
      impermeable coating cup consisted of cellulose acetate propionate and the top
      cover layer of hydrophilic swellable materials, such as polyethylene oxide,
      sodium alginate or sodium carboxymethyl cellulose. The effect of the core, the
      polymer characteristics and quantity at the top cover layer, on the lag time and
      drug release was investigated. The results show that the system release of the
      drug after a certain lag time generally due to the erosion of the top cover
      layer. The quantity of the material, its characteristics (viscosity, swelling,
      gel layer thickness) and the drug solubility was found to modify lag time and
      drug release. The lag time increased when the quantity of top layer increased,
      whereas drug release decreased. The use of sodium carboxymethyl cellulose
      resulted in the greatest swelling, gel thickness and lag time, but the lowest
      drug release from the system. Polyethylene oxide showed an intermediate behaviour
      while, the sodium alginate exhibited the smallest swelling, gel thickness and the
      shortest lag time, but the fastest release. These findings suggest that drug
      delivery can be controlled by manipulation of these formulations.

PMID- 16436322
TI  - Allele frequencies of the 15 AmpF/Str Identifiler loci in the population of
      Metztitlan (Estado de Hidalgo), Mexico.
AB  - The 15 AmpF/STR Identifiler loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01,
      D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were
      analyzed in the sample of 180 unrelated autochthonous healthy adults born in
      Meztitlan City from the valley of Metztitlan (Estado de Hidalgo, Mexico). The
      agreement with Hardy-Weinberg equilibrium was confirmed for all loci. From the
      forensic point of view, the heterozygosity value, power of discrimination and the
      a priori chance of exclusion were calculated.

PMID- 16436323
TI  - Shaken baby syndrome: a flawed biomechanical analysis.

PMID- 16436324
TI  - Local mechanical properties of mouse outer hair cells: atomic force microscopic
      study.
AB  - OBJECTIVES: Outer hair cells (OHCs) are capable of altering their cell length in
      response to changes in membrane potential. Due to this electromotility, OHCs
      probably subject the basilar membrane to force, resulting in cochlear
      amplification. To understand the mechanism of such amplification, knowledge of
      the mechanical properties of OHCs is required since the force produced by OHC
      electromotility is thought to depend on such properties. Various studies have
      been conducted to investigate the mechanical properties of guinea pig OHCs. With
      regard to mice, however, although various kinds of transgenic and knockout mice
      possess great potential as research models, the mechanical properties of mouse
      OHCs have not as yet been reported since the cells and/or tissues in the mouse
      hearing organ are relatively small and vulnerable to external stimuli, rendering
      sample preparation difficult. In this study, therefore, to establish indicators
      of the mechanical properties of OHCs in mice, such properties were measured by
      atomic force microscopy (AFM). METHODS: CBA/JNCrj strain male mice aged 10-12
      weeks (25-30 g) were used. Cochleae were dissected out from the animal and both
      the basilar membrane and the organ of Corti were simultaneously unwrapped from
      the modiolus with forceps. Dissected coiled tissue was then incubated with an
      enzymatic digestion medium for 15 min. After digestion, OHCs were isolated by
      gently triturating the coiled tissue. Local mechanical properties of the OHCs
      were then measured by an indentation test using an AFM. RESULTS: Young's modulus
      and stiffness of the OHC in the apical turn of the mouse cochlea were 2.1+/-0.5
      kPa and 4.4+/-1.2 mN/m, respectively. CONCLUSIONS: Young's modulus of the OHC in
      the apical turn of the cochlea in mice was roughly the same as that in the apical
      turn of the cochlea in guinea pigs; however, the stiffness of the former was
      about two times greater than that of the latter because the cell length of the
      former was shorter than that of the latter.

PMID- 16436325
TI  - Degenerative spine disorders in the context of clinical findings.
AB  - Hardly any other structure in the human body is held responsible for so many
      complaints, pain, and costs as the spine and its degenerative disorders. In the
      following article, the role of imaging procedures in diagnosing disorders of the
      spine is presented. Due to the fact that disk herniation represents the most
      frequent cause for degenerative disorders the anatomy of the intervertebral disk
      and the pathology of the entities that can cause diseases of the disks are
      described. In particular, the authors focus on the significance of radiological
      findings with respect to patient history, subjective symptoms, and objective
      clinical findings. In addition to presenting the technical procedures and their
      indications and contraindications also practical tips and tricks in conducting
      these examinations are presented in this paper.

PMID- 16436326
TI  - Herminiimonas aquatilis sp. nov., a new species from drinking water.
AB  - A bacterial strain (CCUG 36956T) isolated from drinking water was taxonomically
      studied in detail. Phylogenetic analyses using the 16S rRNA gene sequence of the
      isolate indicated that it belongs to family Oxalobacteraceae of the beta-subclass
      of the Proteobacteria, with the highest sequence similarity of 99.3% to the type
      strain of Herminiimonas fonticola. In the polyamine pattern putrescine and 2
      hydroxyputrescine were the predominant compounds. In the polar lipid profile
      major compounds were phosphatidyl ethanolamine and diphosphatidyl glycerol.
      Phosphatidyl glycerol and an unknown phospholipid were detected in moderate
      proportions. The major respiratory quinone was a ubiquinone Q-8 and the major
      whole cell fatty acids were 16:1 omega7c, 17:1 omega6c, and 16:0. The strain also
      contained 10:0 3-OH and other fatty acids typical for members of the genus
      Herminiimonas. The results of DNA-DNA hybridizations and physiological and
      biochemical tests allowed genotypic and phenotypic differentiation of strain CCUG
      36956T from H. fonticola. For this reason, we propose that strain CCUG 36956T
      represents a new species of the genus Herminiimonas for which we propose the name
      Herminiimonas aquatilis sp. nov.

PMID- 16436327
TI  - The development of a scale to discover outpatients' perceptions of the relative
      desirability of different elements of doctors' communication behaviours.
AB  - OBJECTIVE: The objective of the study was to discover which aspects of doctor
      communication behaviours are more or less desirable to patients who are attending
      medical outpatients clinics. METHODS: Two hundred and twenty patients took part
      in the study, which was undertaken in four phases. In phase one, patients
      completed a 10-item questionnaire where they indicated, by means of a five-point
      scale, their preferences for doctor communication behaviours. In phases two and
      three patients qualitatively expressed the meaning that they ascribed to
      terminology that is used by some researchers to define doctor communication
      behaviours. In the final phase of the study a 12-item questionnaire was developed
      by integrating the phase one questionnaire and patients' report from phases two
      and three. Patients indicated, by means of a five-point scale, their preferences
      for different communication behaviours that might be used by doctors. Patient's
      preferences were ranked in terms of the most to the least preferred behaviours.
      RESULTS: The findings suggest that patients most prefer consultations where
      doctors give information spontaneously and display affective behaviours. They
      least preferred consultations where medical matters are discussed and where
      information is not forthcoming. Furthermore, the finding suggests that the use of
      blanket terms by researches in defining doctor communication can lead to
      differences in interpretation by patients. CONCLUSIONS: The methods developed in
      the study appear to provide a useful tool to discover patients' desires in terms
      of doctor communication. PRACTICE IMPLICATIONS: The rank scale developed in the
      study could prove useful to medical practice. It could, for example, provide a
      straightforward method whereby doctors could readily access researcher's
      recommendations about communication. Furthermore, the scale could be used in
      various healthcare settings in order to discover if different patient groups vary
      in terms of the doctor communication they desire.

PMID- 16436328
TI  - Preparation and in vivo evaluation of (99m)TcN-tertiary butyl xanthate as a
      potential myocardial agent.
AB  - (99m)Tc-tertiary butyl isonitrile (TBI), a complex structurally similar to
      (99m)Tc-sestamibi, has been reported to be taken up in the myocardium, albeit
      with significant retention in liver and lungs, thereby leading to obscure heart
      images when used for in vivo imaging. In the present study, tert-butyl xanthate,
      which is similar to TBI, but possesses two sulphur donors, has been synthesized
      in excellent yield by reacting tert-butanol with carbon disulphide and sodium
      hydroxide in dry ether. The prepared ligand was then labeled with [(99m)TcN]2+
      core and the resultant complex was characterized by paper electrophoresis and
      HPLC. The complex was obtained in more than 95% yield and was found to be
      neutral. The preparation was evaluated in Swiss mice for its myocardial perfusion
      characteristics. The maximum heart uptake observed was 2.34%ID/g at 5 min p.i.,
      which was cleared rapidly, with retention of 0.50%ID/g of the activity at 60 min
      p.i. However, owing to slow clearance from blood, liver and lungs, the
      heart/blood, heart/liver and heart/lung ratios at all the time points of study
      were not significantly high.

PMID- 16436329
TI  - Fading magic of maze procedure.

PMID- 16436330
TI  - Old and new perspectives in the pharmacological treatment of advanced or
      recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly
      targeted therapies.
AB  - Hormonal therapy and chemotherapy play a major role in the management of advanced
      or recurrent endometrial cancer. Progesterone therapy obtains overall response
      rates ranging from 11% to 25% in patients with endometrioid-type tumours, and
      oral medroxyprogesterone acetate 200mg daily appears to be a reasonable
      therapeutic option for those lesions that are well differentiated and/or have a
      high progesterone receptor (PgR) content. However, the activity of progestins is
      often compromised by the down-regulation of PgR within the target tissues, and
      therefore therapeutic strategies designed to enhance PgR expression are
      warranted. Little data are currently available about the new aromatase inhibitors
      and selective estrogen receptor modulators. As for chemotherapy, the combination
      of doxorubicin [DOX]+cisplatin [CDDP] achieves overall response rates ranging
      from 34% to 60%, and the addition of paclitaxel (TAX) seems to improve response
      rates, progression-free survival and overall survival, but to worsen toxicity
      profile. A phase III study is currently comparing TAX+DOX+CDDP versus the less
      toxic combination of TAX+carboplatin. Chemotherapy is active against both
      endometrioid-type carcinoma and uterine serous papillary carcinoma. However, this
      latter endometrial malignancy is less chemosensitive than the histologically
      similar high-grade serous ovarian carcinoma. Interesting fields of research are
      represented by investigational agents directed against specific intracellular
      signal transduction pathways involved in the proliferation, invasiveness and
      metastatic spread of endometrial cancer. Mammalian target of the rapamycin (mTOR)
      inhibitors, epidermal growth factor receptor inhibitors (gefitinib, erlotinib,
      lapatinib, the monoclonal antibody cetuximab), imatinib, the monoclonal antibody
      trastuzumab, and the Clostridium perfrigens enterotoxin are currently under
      evaluation as molecularly targeted therapies for endometrial cancer. Further
      investigations addressed to better understand the signal transduction pathways
      that are disregulated in endometrial carcinogenesis could identify novel
      biological targets suitable for tailored therapies.

PMID- 16436332
TI  - Plasma amino acid profiles applied for diagnosis of advanced liver fibrosis in
      patients with chronic hepatitis C infection.
AB  - Although biopsy has been considered mandatory in diagnosing liver fibrosis, there
      is a high demand for alternative effective and noninvasive methods. In this study
      we aimed to develop a noninvasive and effective method using the plasma amino
      acid profiles for the diagnosis of liver fibrosis. MATERIALS AND METHODS: Fifty
      three patients with chronic hepatitis C infection were included in the study.
      Plasma amino acid concentration was analyzed and severity of fibrosis was staged
      based on biopsy. We employed a previously published amino acid-based approach to
      develop a discriminator (designated as an "amino-index") for the diagnosis of
      patients with advanced liver fibrosis. The area under the receiver operating
      characteristic curve (AUC) was used for evaluation of the diagnosis. RESULTS:
      (Phe)/(Val)+(Thr+Met+Orn)/(Pro+Gly) was derived as the optimal amino index. The
      AUCs were 0.92+/-0.04 (SE) and 0.99+/-0.01 for discriminating advanced fibrosis
      (fibrosis stages F3 and F4) and for discriminating cirrhosis, respectively. By
      use of the optimal cut-off values, both the sensitivity and specificity achieved
      a score over 0.88. CONCLUSION: Fibrosis index based on amino acid concentration
      could be applied to diagnose liver fibrosis as a convenient noninvasive approach.

PMID- 16436331
TI  - Propionyl-L-carnitine prevents the progression of cisplatin-induced
      cardiomyopathy in a carnitine-depleted rat model.
AB  - This study has been initiated to investigate whether endogenous carnitine
      depletion and/or carnitine deficiency is a risk factor during development of
      cisplatin (CDDP)-induced cardiomyopathy and if so, whether carnitine
      supplementation by propionyl-L-carnitine (PLC) could offer protection against
      this toxicity. To achieve the ultimate goal of this study, a total of 60 adult
      male Wistar albino rats were divided into six groups. The first three groups were
      injected intraperitoneally with normal saline, PLC (500 mg kg(-1)), and d
      carnitine (500 mg kg(-1)) respectively, for 10 successive days. The 4th, 5th, and
      6th groups were injected intraperitoneally with the same doses of normal saline,
      PLC and D-carnitine, respectively, for 5 successive days before and after a
      single dose of CDDP (7 mg kg(-1)). On day 6 after CDDP treatment, animals were
      sacrificed, serum as well as hearts were isolated and analyzed. CDDP resulted in
      a significant increase in serum creatine phosphokinase isoenzyme (CK-MB) and
      lactate dehydrogenase (LDH), thiobarbituric acid reactive substances (TBARS) and
      total nitrate/nitrite (NO(x)) and a significant decrease in reduced glutathione
      (GSH), total carnitine, and adenosine triphosphate (ATP) content in cardiac
      tissues. In the carnitine-depleted rat model, CDDP induced dramatic increase in
      serum cardiomyopathy enzymatic indices, CK-MB and LDH, as well as progressive
      reduction in total carnitine and ATP content in cardiac tissue. Interestingly,
      PLC supplementation resulted in a complete reversal of the increase in cardiac
      enzymes, TBARS and NO(x), and the decrease in total carnitine, GSH and ATP,
      induced by CDDP, to the control values. Moreover, histopathological examination
      of cardiac tissues confirmed the biochemical data, where PLC prevents CDDP
      induced cardiac degenerative changes while d-carnitine aggravated CDDP-induced
      cardiac tissue damage. In conclusion, data from this study suggest for the first
      time that carnitine deficiency and oxidative stress are risk factors and should
      be viewed as mechanisms during development of CDDP-related cardiomyopathy and
      that carnitine supplementation, using PLC, prevents the progression of CDDP
      induced cardiotoxicity.

PMID- 16436333
TI  - Selective transfer of energy through an alamethicin-doped artificial lipid
      membrane studied at discrete molecular level.
AB  - In this study we present novel evidence that strengthens the paradigm of
      selective transfer of energy mediated by a random gating of ion channels.
      Specifically, we investigated the spectral response of a noisy artificial
      biomembrane whose electrical properties were largely dictated by embedded
      alamethicin oligomers. In this respect, we first evaluated experimentally the
      linear transfer function of the system via the white-noise analysis method. We
      prove that such a system displays specific ranges of frequency over which input
      signals pass preferentially, depending on their spectral content and the holding
      potential across the artificial bilayer which contains alamethicin. By employing
      voltage-driven periodic stimulation of alamethicin oligomers, we demonstrate that
      overall response of the system obeys qualitatively the predictions inferred from
      the transfer function analysis of it. These results emphasize the exquisite
      ability of excitable membranes to behave as band-limited filters and allow for
      maximal transfer of energy from an external stimulus over well-defined frequency
      ranges.

PMID- 16436334
TI  - Determination of drugs of abuse and their metabolites in human plasma by liquid
      chromatography-mass spectrometry. An application to 156 road fatalities.
AB  - A method, using 0.2 ml of plasma, was designed for the simultaneous determination
      of morphine, 6-monoacetylmorphine, amphetamine, methamphetamine, MDA, MDMA, MDEA,
      MBDB, benzoylecgonine and cocaine. The drugs were analysed by LC-MS, after solid
      phase extraction in the presence of the deuterated analogues. Reversed phase
      separation on an Atlantis dC18 column was achieved in 10 min, under gradient
      conditions. The method was full validated, including linearity (2-250 ng/ml,
      r2>0.99), recovery (>50%), within-day and between-day precision and accuracy (CV
      and bias <15%), limit of detection (0.5 and 1 ng/ml) and quantitation (2 ng/ml),
      relative ion intensities and no matrix effect was observed. The procedure showed
      to be sensitive and specific, and was applied to 156 real cases from road
      fatalities (7.1% cases positive to cocaine and 0.6% to designer drugs).

PMID- 16436335
TI  - Gluten intolerance and skin diseases.
AB  - Gluten sensitivity with or without coeliac disease (CD) symptoms and intestinal
      pathology has been suggested as a potentially treatable cause of various
      diseases. CD is a chronic disease which improves on withdrawal of wheat gliadins
      and barley, rye and oat prolamins from the diet. There have been numerous reports
      linking CD with several skin conditions. A body of evidence shows that dermatitis
      herpetiformis is actually a cutaneous manifestation of CD. Autoimmune diseases,
      allergic diseases, psoriasis and miscellaneous diseases have also been described
      with gluten intolerance. Dermatologists should be familiar with the appraisal of
      gluten sensitive enteropathy and should be able to search for an underlying
      gluten intolerance (GI). Serological screening by means of antigliadin,
      antiendomysial and transglutaminase antibodies should be performed. HLA typing is
      often useful in association with serologic tests. Intestinal biopsy is usually
      needed to establish the diagnosis of CD or GI. Thus, gluten intolerance gives
      rise to a variety of dermatological manifestations which may benefit from a
      gluten-free diet.

PMID- 16436336
TI  - Dendritic cells and toll-like receptors in allergy and asthma.
AB  - Epithelia represent a major portal of entry for pathogen microorganisms and
      allergens and are equipped with innate and adaptive immunity for their
      protection. Pattern recognition receptors (PRR), including Toll-Like Receptors
      (TLR), recognize pathogen-associated molecular patterns (PAMP) shared by numerous
      microorganisms. TLR engagement is involved in innate immunity but also
      participates in the control of the adaptive immune response, which may be
      involved in the pathophysiology of allergic diseases like asthma. Experimental
      studies have largely demonstrated the implication of TLR in both development and
      control of the allergic reaction. Dendritic cells (DC), which play a key role in
      these processes, are a privileged target for PAMP. During the allergic reaction,
      TLR engagement on DC directs the polarization of the T cell response and, while
      TLR2 and TLR4 may favour both Th1 and Th2 responses, TLR9 induces the development
      of regulatory T cells.

PMID- 16436337
TI  - Vitiligo vs. hypopigmented mycosis fungoides (histopathological and
      immunohistochemical study, univariate analysis).
AB  - Vitiligo is a common skin disease characterized by the presence of well
      circumscribed, depigmented milky white macules devoid of identifiable
      melanocytes. On the other hand, hypopigmented mycosis fungoides (MF) is a rare
      variant of MF which presents clinically as persistent hypopigmented macules and
      patches. Both disorders show a predominance of CD8+ T cells in tissue samples and
      hence the differentiation between the two diseases on clinical, histopathological
      and even immunohistochemical grounds may offer great difficulty. The aim of this
      work is to identity certain histopathological clues which might help to
      differentiate between the two diseases. The study included 54 patients (26
      vitiligo patients and 28 patients with Hypopigmented MF). Skin biopsies were
      taken and examined by hematoxylin and eosin and CD3, CD4 and CD8 markers were
      performed for ten vitiligo and nine MF patients. We have found that
      epidermotropism, hydropic degeneration of basal cells, partial loss of pigment,
      preservation of some melanocytes, presence of lymphocytes within the papillary
      dermis, increased density of the dermal infiltrate and wiry fibrosis of the
      papillary dermal collagen were detected with a significantly higher incidence in
      hypopigmented MF rather than vitiligo (P-values < 0.0001, < 0.00011, < 0.00011, =
      0.001, = 0.008 and = 0.001 respectively). On the other hand, focal thickening of
      the basement membrane, complete loss of pigmentation, total absence of
      melanocytes, as well as absence or sparsness of lymphocytes in the dermal
      papillae were seen much more frequently in vitiligo. Statistical analysis of
      these differences was significant with P-values < 0.00011, < 0.00011, < 0.00011,
      = 0.008 respectively, regarding these pathological criteria. We conclude that
      differentiation of hypopigmented MF from vitiligo is possible by relying on the
      histopathological clues described in this study. This is particularly useful in
      areas of the world where cost benefit is crucial.

PMID- 16436338
TI  - Plantar skin in type II diabetes: an investigation of protein glycation and
      biomechanical properties of plantar epidermis.
AB  - The generation of thickened plantar stratum corneum (SC) in response to elevated
      pressures, places individuals with diabetes at risk of ulceration. Such a
      response may culminate from altered biochemical and physical states of the
      epidermis as a result of non-enzymatic glycation (NEG). The objective of this
      study was to quantify specific glycation products generated in plantar epidermal
      proteins in individuals with Type 2 Diabetes Mellitus (T2DM) and age-matched
      controls (n = 103 and n = 87, respectively) and to compare these data with the
      viscoelastic properties (in vivo) of the epidermis. Plantar SC and venous blood
      samples were collected from all participants for the quantification of furosine
      and pentosidine using high performance liquid chromatography (HPLC). The
      viscoelastic properties of plantar epidermis were measured by the application of
      negative pressure on the surface of the skin. Plantar epidermal thickness was
      measured using high frequency (20 MHz) ultrasonography. There was a significantly
      greater concentration of pentosidine in the SC samples from people with T2DM (p =
      0.001). There was no correlation between the concentration of glycated proteins
      in the epidermal proteins and serum proteins (furosine r = - 0.115, pentosidine r
      = - 0.023). The plasticity of the epidermis was significantly lower in the T2DM
      group than the control group (p = 0.007). The results suggest that alterations in
      the glycation of plantar epidermal proteins may constitute additional aggravators
      of ulceration in people with T2DM.

PMID- 16436339
TI  - Study on the expression of RXRalpha in patients with psoriasis vulgaris.
AB  - Retinoic acid regulates keratinocyte proliferation and differentiation--processes
      that are disturbed in psoriatic skin--via binding to nuclear receptors, including
      retinoic acid receptor (RAR-alpha,beta,gamma) and the common heterodimer partners
      (RXR-alpha,beta,gamma). By RT-PCR and immunohistochemistry methods, the
      expression of RXRalpha was studied in psoriatic skin and controls. The expression
      of RXRalpha was down-regulated in patients with psoriasis; moreover, its level
      was related to the stage of the disease; in the progressive stage of the disease,
      the level of the RXRalpha was lower than in the stable stage. The results suggest
      that retinoid signaling is abnormal in lesional psoriatic skin, RXRalpha
      expression is mainly confined to differentiated keratinocytes.

PMID- 16436340
TI  - Photodynamic therapy for superficial basal cell carcinoma and Bowen's disease.
AB  - Photodynamic therapy (PDT) is an effective treatment for superficial basal cell
      carcinoma (BCCs) and Bowen's disease. Several studies have reported complete
      response rates of 80-95% and an excellent cosmetic outcome. Bowen's disease and
      superficial basal cell carcinomas characteristically affect older patients who
      may also have associated difficulties with mobility. Using a portable PDT light
      source we were able to deliver PDT in a community setting with the aim of
      providing a more convenient service for patients. This randomised study confirmed
      that community delivered PDT is a viable treatment option and can be administered
      safely in the community by a trained dermatology nurse. The results from patient
      questionnaires suggest that community delivered PDT is more convenient to the
      patient, and also cost effective.

PMID- 16436341
TI  - Usefulness of itraconazole for sporotrichosis in Japan: study of three cases and
      literature comparison of therapeutic effects before and after release on the
      market.
AB  - Potassium iodide, itraconazole (ITCZ), and terbinafine are widely known as oral
      antifungal agents for the treatment of sporotrichosis. Although potassium iodide
      has been used as the antifungal agent of first choice in Japan due to its high
      efficacy, its use is not covered by the health insurance programs. In this
      report, we present the disease course of 3 patients with sporotrichosis in which
      ITCZ was remarkably effective. By reviewing cases reported in the past, we found
      sufficient therapeutic effects of ITCZ against sporotrichosis. We also conducted
      a simple comparison of the efficacy of ITCZ in clinical trials with that of its
      post-market release; finding the latter to be lower. This seems to be
      attributable to the problem of compliance or the administration method.

PMID- 16436342
TI  - Clinical and bacteriological evaluation of nadifloxacin 1% cream in patients with
      acne vulgaris: a double-blind, phase III comparison study versus erythromycin 2%
      cream.
AB  - The aim of this double-blind, multinational, phase III study was to investigate
      the clinical and bacteriological efficacy of nadifloxacin 1% cream compared with
      erythromycin 2% cream in 474 European patients with predominantly inflamed slight
      to-moderate acne vulgaris. During 12 weeks of treatment both nadifloxacin and
      erythromycin caused significant reduction in the number of inflamed papulo
      pustular lesions (66.7% and 64.7%, respectively) and open and closed comedones.
      The microbiological evaluation showed a significant reduction of coagulase
      negative staphylococci (CNS) only in the nadifloxacin group, while
      Propionibacterium acnes was significantly reduced by both formulations. A
      significantly higher resistance and the extent of resistant of P. acnes and CNS
      against erythromycin compared to nadifloxacin were also evidenced. All adverse
      events reported were minor in both groups. This pivotal erythromycin-controlled
      study has demonstrated that nadifloxacin 1% cream was as efficacious and safe as
      erythromycin 2% and extremely low numbers of nadifloxacin-resistant
      microorganisms were detected in the treatment period.

PMID- 16436343
TI  - Efficiency of topical imiquimod 5% cream in the management of chronic radiation
      dermatitis with multiple neoplasias.
AB  - The immune response modifier imiquimod 5% cream (Aldara) was locally applied to
      an extensive thoracic chronic radiation dermatitis for 2 weeks on a once daily
      basis. After moderate to severe irritative reactions with erythema and crusted
      erosions, areas cleared up within 4 weeks. The patient has now been in complete
      remission for 2 years.

PMID- 16436344
TI  - Linear Darier's disease successfully treated with 0.1% tazarotene gel "short
      contact" therapy.
AB  - We report the case of a 25 year old man affected by linear Darier's disease. The
      patient presented with brownish keratotic papules involving the trunk in a linear
      pattern. These lesions were successfully treated within 6 weeks with 0.1%
      tazarotene gel "short contact". The good response that was obtained suggests that
      the use of "short contact" tazarotene could be useful in the treatment of linear
      Darier's disease.

PMID- 16436345
TI  - Adult-onset infective dermatitis associated with HTLV-I. Clinical and
      immunopathological aspects of two cases.
AB  - Infective dermatitis associated with HTLV-I (IDH) is a chronic, infected
      childhood eczema. Two adult-onset cases of IDH were studied, one of which was
      associated with HAM/TSP. The patients were submitted to dermatological,
      neurological and pathological examination. Immunohistochemical studies were made
      using CD3, CD4, CD8, CD20, CD79a, and CD57 antibodies. Cytotoxic granules were
      investigated using granzyme B, perforin, and TIA. The patients presented infected
      erythematous, scaly lesions with mild itching and a good response to
      sulfamethoxazole/ trimethoprim. A differential diagnosis with atopic dermatitis
      (AD) and seborrheic dermatitis (SD) was made, based on: the distinctive
      morphology and distribution of the lesions, presence of exudative and infected
      lesions, and mild pruritus. The inflammatory infiltrate was composed
      predominantly of CD8+ lymphocytes that did not present cytotoxic granules. We
      concluded that IDH can begin in adulthood and may be associated with HAM/TSP. The
      immunohistochemical findings were different from those observed in AD and SD.

PMID- 16436346
TI  - Lipoprotein (a) and nitrites in Behcet's disease: relationship with disease
      activity and vascular complications.
AB  - Our objective was the assessment of serum lipoprotein(a) {Lp(a)} and nitrites in
      Behcet's disease (BD) patients and their relation to vascular events and disease
      activity. Thirty cases of BD and 14 healthy volunteers were included. Serum
      levels of Lp(a) were estimated using enzyme-linked immunosorbent assays. Serum
      nitrites were measured according to the method of Benjamin and Vallence. Compared
      to controls, BD patients had significantly lower concentrations of serum
      nitrites, and significantly higher concentrations of Serum Lp(a). Significantly
      higher levels of serum Lp(a) were observed in patients with vascular
      complications, while significantly lower levels of serum nitrites were found
      during disease activity and in patients with erythema nodosum like lesions.
      Increased serum lipoprotein (a) may contribute to the increased incidence of
      vascular complications in Behcet's disease. Decreased nitrites can be considered
      as a marker of disease activity that may be related to endothelial dysfunction.

PMID- 16436347
TI  - Skin vasculitis during Creutzfeldt-Jakob's disease.
AB  - We report the case of a 72-year-old woman with sporadic Creutzfeldt-Jakob's
      disease who presented a large purplish erythematous and edematous lesion, with
      subsequent bullous detachment on the anterior right thigh. The lesion rapidly
      evolved into an ulcer covered by a blackish necrotic eschar. Histological
      examination showed intense necrotizing leukocytoclastic vasculitis in the deep
      and middle dermis. Direct immunofluorescence revealed C3 and IgM deposits around
      vessels of the middle and deep dermis. The diagnosis of sporadic Creutzfeldt
      Jacob's was confirmed post-mortem by immunoblotting on frozen brain tissue which
      showed pathologic proteinase-resistant prion-related protein isoform glycotype
      2A. In the literature, only two cases of Creutzfeldt-Jakob's disease and
      cutaneous manifestations are reported.

PMID- 16436348
TI  - Genital Paget's disease in a man.
AB  - Pagetoid cells are large intraepidermal cells which spread intraepidermally. We
      report a 67-year old Caucasian male, who presented for the first time in 1993
      with a long-standing pruritic lesion at the scrotum. He was treated for several
      years by antiinflammatory ointments. Only in July 2003 was a biopsy taken for the
      first time. The histopathological evaluation revealed the diagnosis of an
      extramammary Paget's disease (EMPD). Pagetoid cells are large intraepidermal
      cells with a large nucleus and ample cytoplasm. EMPD consists of primary
      malignant cells of epidermal origin, but in rare cases, pagetoid cells may also
      originate from carcinomas with epidermotropic growth. EMPD is a slowly
      progressing disease, but invading and metastasing tumors may also develop.
      Considering the good prognosis with long-term survival, nonsurgical modalities
      should be considered as primary treatment for noninvasive EMPD.

PMID- 16436349
TI  - Disseminated Mycobacterium marinum infection with extensive cutaneous eruption
      and bacteremia in an immunocompromised patient.
AB  - Mycobacterium marinum can cause fish tank granuloma (or swimming pool or aquarium
      granuloma) in immunocompetent patients. Dissemination of Mycobacterium marinum
      infection is a rare condition which occurs mainly in immunocompromised patients
      and can be life-threatening. We report the case of an 87-year-old woman who was
      treated with oral corticosteroids for polymyalgia rheumatica for many years and
      developed erythema nodosum-like lesions on the right forearm and arthritis of the
      right wrist. By increasing the steroid dosage and adding methotrexate only short
      term remission was achieved. Seven months later painful erythematous nodules
      occurred on all extremities which became necrotic, ulcerative and suppurative.
      Ziehl-Neelsen staining revealed acid-fast bacilli and Mycobacterium marinum was
      cultured from skin biopsies, blood, and urine. The critically ill patient was
      treated with clarithromycin and ethambutol resulting in a dramatic improvement of
      the general condition. After four months, doxycycline had to be added because of
      new skin lesions. This case illustrates the impact of Mycobacterium marinum
      infection in immunocompromised patients.

PMID- 16436350
TI  - Mycosis fungoides palmaris et plantaris--an unusual variant of cutaneous T-cell
      lymphoma.
AB  - Mycosis fungoides (MF) represents a low-risk, cutaneous, non-Hodgkin, T-cell
      lymphoma with a wide spectrum of clinicopathological manifestations and therefore
      may mimic a number of other dermatoses. Sometimes the clinical diversity makes
      the diagnosis of MF, and especially its atypical forms, challenging. We report on
      an 18-year old male patient, who had been previously diagnosed with palmoplantar
      eczema. Clinical, histopathological, immunohistochemical and molecular findings
      revealed an atypical case of MF.

PMID- 16436351
TI  - Elephantine nose due to rhinoentomophthoromycosis.
AB  - Rhinoentomophthoromycosis in an immunocompetent Indian male due to Basidiobolus
      species resulting in a huge (elephantine) nasal deformity, is reported. The
      diagnosis was done by demonstration of hyphae in direct tissue smear examination
      in potassium hydroxide, histopathological examination and by cultural
      characteristics. He showed an excellent response to oral potassium iodide
      solution.

PMID- 16436352
TI  - Multiple cutaneous squamous cell carcinomas arising in a patient with generalized
      morphea.
AB  - Association of cutaneous scleroderma and squamous cell carcinoma (SCC) has been
      reported in a few cases. We report a new case of multiple SCC which occurred in
      sclerotic patches on the leg. The role of factors explaining this association is
      discussed as immunosuppression or ulcerations.

PMID- 16436353
TI  - Sclerodermatous chronic graft-versus-host disease presenting with dysphagia.

PMID- 16436354
TI  - LVMH Recherche Symposium Mitochondria October 6 th, 2005, Paris.

PMID- 16436357
TI  - Psychological processes and neural mechanisms for action: the legacy of Steven W.
      Keele.
AB  - The recent untimely illness and death of Steven W. Keele is a great loss for
      psychology in general and for the field of motor control in particular. Steve
      Keele was a pioneer in the study of the psychological processes and neural
      mechanisms underlying attention and motor control. Steve was a Consulting Editor
      for the Journal of Motor Behavior from 1969 to 1974 and served on the Editorial
      Board from 1974 to 1977, and again from 1980 until his retirement in 1997. Steve
      served as head of the University of Oregon Psychology Department from 1992-1995,
      and, although he retired in 1997, he continued to perform important research
      until he became ill in early 2005.

PMID- 16436358
TI  - Neuromuscular-skeletal origins of predominant patterns of coordination in
      rhythmic two-joint arm movement.
AB  - The authors tested for predominant patterns of coordination in the combination of
      rhythmic flexion-extension (FE) and supination- (SP) at the elbow-joint complex.
      Participants (N=10) spontaneously established in-phase (supination synchronized
      with flexion) and antiphase (pronation synchronized with flexion) patterns. In
      addition, the authors used a motorized robot arm to generate involuntary SP
      movements with different phase relations with respect to voluntary FE. The
      involuntarily induced in-phase pattern was accentuated and was more consistent
      than other patterns. The result provides evidence that the predominance of the in
      phase pattern originates in the influence of neuromuscular-skeletal constraints
      rather than in a preference dictated by perceptual-cognitive factors implicated
      in voluntary control. Neuromuscular-skeletal constraints involved in the
      predominance of the in-phase and the antiphase patterns are discussed.

PMID- 16436359
TI  - Upper and lower limb reciprocal tapping: evidence for gender biases.
AB  - According to D. Kimura's (2000) interpretation of the hunter-gatherer hypothesis,
      men are better at targeting tasks and women are better at fine-motor tasks
      because of their evolutionary experiences. The author applied that hypothesis to
      a lower limb pointing task, a task uninfluenced by hunting and gathering
      experience throughout history. Participants (39 women, 35 men) completed the P.
      M. Fitts (1954) task by using both their dominant right hand and foot. Results
      suggested that for both the upper and lower limbs, men move faster, particularly
      for the more difficult tasks. The hunter-gatherer hypothesis does not predict
      those data; rather, linear regression data suggest that gender differences in
      movement strategies affect motor performance. The author proposes that men and
      women preferentially adopt distinct strategies emphasizing speed for men and
      accuracy for women.

PMID- 16436360
TI  - A note on time-frequency analysis of finger tapping.
AB  - Finger tapping involves 3 important features: time, spatial amplitude, and
      frequency. In classical analysis, investigators examine timing parameters; in
      spectral analysis, they examine frequency parameters. Both types of analysis are
      based on stationary tap information. The authors propose that time-frequency
      analysis is a useful tool for analyzing nonstationary finger tapping. They
      describe the method and give examples of frequency modulation, age difference,
      and speed transition that demonstrate additional insights one can gain by using
      this analysis.

PMID- 16436362
TI  - Motor deficits in Parkinsonian reaching: dopa-sensitivity influenced by real
      world task constraint.
AB  - Parkinson's disease (PD) patients can perform many daily activities, but movement
      deficits are evident. Those deficits may be increased when the required movement
      is constrained in accuracy. Variable improvements in performance with PD
      medication have been demonstrated, and sensitivity to task constraint has been
      evident in some studies. The authors quantified both specific movement deficits
      and improvements for PD patients in a reaching task. PD patients (N=8) both on
      and off medication showed a need for greater ongoing control in movements with
      higher task-accuracy constraints. Increased task-accuracy constraints further
      compromised movement timing and structure among PD patients who were off
      medication, suggesting that unmedicated PD patients may typically compensate by
      using more conscious control of movement, resulting in increased slowing and
      segmentation of components when higher task accuracy is required.

PMID- 16436363
TI  - Learning of similar complex movement sequences: proactive and retroactive effects
      on learning.
AB  - The authors used an interference paradigm to determine the extent to which the
      learning of 2 similar movement sequences influences the learning of each other.
      Participants (N=30) produced the sequences by moving a lever with their right arm
      and hand to sequentially presented target locations. They practiced 2 similar 16
      element movement sequences (S1 and S2), 1 sequence on each of 2 consecutive days
      of practice. Control groups received only 1 day of practice on 1 of the
      sequences. Early in S2 practice, the experimental group demonstrated a relatively
      strong level of proactive facilitation arising from previous practice with S1.
      The advantage was not evident at the end of S2 practice or on the S2 retention
      test. No advantage of practicing the 1st sequence on the learning of the 2nd
      sequence (proactive effect) was found in the analysis of element duration in the
      retention and transfer tests, even though 14 of the 16 elements were common to
      both sequences. A strong retroactive interference on the switched elements was
      detected, however. Thus, the memories underpinning S1 seemed to be "overwritten"
      or adapted in response to the learning of S2.

PMID- 16436361
TI  - The role of vision in the control of continuous multijoint movements.
AB  - The authors investigated whether visual fixations during a continuous graphical
      task were related to arm endpoint kinematics, joint motions, or joint control.
      The pattern of visual fixations across various shapes and the relationship
      between temporal and spatial events of the moving limb and visual fixations were
      assessed. Participants (N=16) performed movements of varying shapes by rotating
      the shoulder and elbow joints in the transverse plane at a comfortable pace.
      Across shapes, eye movements consisted of a series of fixations, with the eyes
      leading the hand. Fixations were spatially related to modulation of joint motion
      and were temporally related to the portions of the movement where curvature was
      the highest. Gathering of information related to modulation of interactive
      torques arising from passive forces from movement of a linked system occurred
      when the velocity of the movement (a) was the lowest and (b) was ahead of the
      moving limb, suggesting that that information is used in a feedforward manner.

PMID- 16436364
TI  - Gender and limb differences in healthy elite dancers: passe kinematics.
AB  - Symmetry of skill development is emphasized in dance training, and many movements
      are well learned by both genders. The authors conducted a 2-dimensional kinematic
      analysis of a complex dance movement, the passe, in 12 healthy professional male
      and female dancers to determine whether there are differences between genders or
      limbs during the performance of that task. Only peak hip angular displacement
      differed in men and women. No differences were found between limbs in any of the
      dependent variables. Dancers displayed consistent temporal and spatial proximal
      to-distal sequencing of movement coordination. Despite an indication of limb
      preference, as defined by gesture or stance limb, there were no differences in
      proficiency.

PMID- 16436365
TI  - Effects of a segmented removable appliance in molar distalization.
AB  - The aim of the present investigation was to evaluate the skeletal and
      dentoalveolar treatment effects of a segmented removable appliance [removable
      molar distalizer (RMD)] for molar distalization. The study was conducted on 28
      patients (12 females and 16 males), with a mean age of 11.8 years. All presented
      with a skeletal Class I malocclusion and a bilateral dental Class II molar
      relationship. The pre- and post-distalization records included lateral head
      films, study models and standard photographs. The findings were evaluated with a
      paired samples t-test. The average maxillary first molar distalization with the
      RMD was 3.98 mm, with 4.61 degrees of distal tipping. The maxillary second
      premolars drifted distally 2.13 mm on average with 1.54 degrees of distal
      tipping, while the maxillary first premolars showed 1.23 mm of mesial movement
      and 1.98 degrees of mesial tipping. The incisors protruded 1.09 mm with 1.27
      degrees of labial tipping. The RMD was effective in distal molar movement and all
      patients attained a bilateral Class I molar relationship in an average period of
      4.5 months. Hygiene problems and mucosal irritations, frequently found with fixed
      intraoral distalization techniques, were not observed during the distalization
      period.

PMID- 16436366
TI  - Occupational and environmental "orphan" respiratory diseases.

PMID- 16436367
TI  - Beta-adrenergic agonist therapy as a potential treatment for acute lung injury.

PMID- 16436368
TI  - Nonspecific triggers also provoke occupational asthma.

PMID- 16436369
TI  - Assessing the role of antiinflammatory medications in children with mild sleep
      disordered breathing.

PMID- 16436370
TI  - Lack of directly observed treatment affects tuberculosis relapse rates.

PMID- 16436371
TI  - Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity.
AB  - Triglyceride synthesis in most mammalian tissues involves the sequential addition
      of fatty acids to a glycerol backbone, with unique enzymes required to catalyze
      each acylation step. Acylation at the sn-2 position requires 1-acylglycerol-3
      phosphate O-acyltransferase (AGPAT) activity. To date, seven Agpat genes have
      been identified based on activity and/or sequence similarity, but their
      physiological functions have not been well established. We have generated a mouse
      model deficient in AGPAT6, which is normally expressed at high levels in brown
      adipose tissue (BAT), white adipose tissue (WAT), and liver. Agpat6-deficient
      mice exhibit a 25% reduction in body weight and resistance to both diet-induced
      and genetically induced obesity. The reduced body weight is associated with
      increased energy expenditure, reduced triglyceride accumulation in BAT and WAT,
      reduced white adipocyte size, and lack of adipose tissue in the subdermal region.
      In addition, the fatty acid composition of triacylglycerol, diacylglycerol, and
      phospholipid is altered, with proportionally greater polyunsaturated fatty acids
      at the expense of monounsaturated fatty acids. Thus, Agpat6 plays a unique role
      in determining triglyceride content and composition in adipose tissue and liver
      that cannot be compensated by other members of the Agpat family.

PMID- 16436372
TI  - Sequence variants in the melatonin-related receptor gene (GPR50) associate with
      circulating triglyceride and HDL levels.
AB  - The gene encoding the melatonin-related receptor (GPR50) is highly expressed
      within hypothalamic nuclei concerned with the control of body weight and
      metabolism. We screened GPR50 for mutations in an obese cohort and identified an
      insertion of four amino acid residues (TTGH) at position 501, two common coding
      polymorphisms (T528A and V602I), and one noncoding polymorphism (C-16X2GPR50T).
      Single-nucleotide polymorphisms were then typed in 500 English Caucasian
      subjects, and associations were sought to intermediate obesity phenotypes.
      Although no association was seen with body mass index, carriers of two copies of
      the mutant allele at C-16X2GPR50T, Ins501Del, and A1582G had significantly higher
      fasting circulating triglyceride levels (P < 0.05). In a separate set of 585
      subjects, the associations were replicated, with statistically significant
      effects of similar magnitude and direction. The association of C-16X2GPR50T with
      fasting triglycerides was highly significant (P < 0.001). In addition, a
      significant association between C-16X2GPR50T and circulating HDL levels was
      observed in the combined population, with C-16X2GPR50T carriers having
      significantly lower circulating HDL-cholesterol levels (1.39 mM) than wild-type
      subjects (1.47 mM) (P < 0.01). These findings suggest a previously unexpected
      role for this orphan receptor in the regulation of lipid metabolism that warrants
      further investigation.

PMID- 16436373
TI  - Insertion of the enteropathogenic Escherichia coli Tir virulence protein into
      membranes in vitro.
AB  - Insertion of the enteropathogenic Escherichia coli Tir protein into the plasma
      membrane of intestinal epithelial cells is a crucial event in infection because
      it provides a receptor for intimate bacterial adherence. This interaction with
      the bacterial outer membrane protein intimin is also essential in generating a
      number of signaling activities associated with virulence. Tir can be modified at
      various sites by phosphorylation and functionally interacts with multiple host
      proteins. To investigate the mechanism of membrane insertion and to establish a
      model system in which the multiple interactions/functions of Tir can be uncoupled
      and independently characterized, we used intrinsic tryptophan fluorescence,
      surface plasmon resonance, and protease digestion assays to show that Tir can
      insert directly into phospholipid vesicles in a composition-dependent manner to
      generate the topology reported in vivo. This is the first time that Tir has been
      shown to insert into membranes in a simple model system in the absence of
      chemical modification or other factors. These data are consistent with the
      protein interacting with lipids through two sites. The major site is localized to
      the transmembrane/intimin-binding domain region and includes Trp235, which is
      shown to be an effective reporter of interaction. The minor site is located
      within the C-terminal domain. Together, these data support a model in which Tir
      is released into the cytoplasm by the type III translocon and then independently
      inserts into the plasma membrane from a cytoplasmic location. A thorough
      understanding of this mechanism will be crucial to understand the subtleties of
      enteropathogenic E. coli pathogenesis.

PMID- 16436374
TI  - Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage
      and in resting cells.
AB  - Ribonucleotide reductase (RNR) provides the cell with a balanced supply of
      deoxyribonucleoside triphosphates (dNTP) for DNA synthesis. In budding yeast DNA
      damage leads to an up-regulation of RNR activity and an increase in dNTP pools,
      which are essential for survival. Mammalian cells contain three non-identical
      subunits of RNR; that is, one homodimeric large subunit, R1, carrying the
      catalytic site and two variants of the homodimeric small subunit, R2 and the p53
      inducible p53R2, each containing a tyrosyl free radical essential for catalysis.
      S-phase-specific DNA replication is supported by an RNR consisting of the R1 and
      R2 subunits. In contrast, DNA damage induces expression of the R1 and the p53R2
      subunits. We now show that neither logarithmically growing nor G(o)/G1
      synchronized mammalian cells show any major increase in their dNTP pools after
      DNA damage. However, non-dividing fibroblasts expressing the p53R2 protein, but
      not the R2 protein, have reduced dNTP levels if exposed to the RNR-specific
      inhibitor hydroxyurea, strongly indicating that there is ribonucleotide reduction
      in resting cells. The slow, 4-fold increase in p53R2 protein expression after DNA
      damage results in a less than 2-fold increase in the dNTP pools in G(o)/G1 cells,
      where the pools are about 5% that of the size of the pools in S-phase cells. Our
      results emphasize the importance of the low constitutive levels of p53R2 in
      mammalian cells, which together with low levels of R1 protein may be essential
      for the supply of dNTPs for basal levels of DNA repair and mitochondrial DNA
      synthesis in G(o)/G1 cells.

PMID- 16436375
TI  - Variable reactivity of an engineered cysteine at position 338 in cystic fibrosis
      transmembrane conductance regulator reflects different chemical states of the
      thiol.
AB  - In a previous study of T338C CFTR (cystic fibrosis transmembrane conductance
      regulator) we found that protons and thiol-directed reagents modified channel
      properties in a manner consistent with the hypothesis that this residue lies
      within the conduction path, but the observed reactivity was not consistent with
      the presence of a single thiolate species in the pore. Here we report results
      consistent with the notion that the thiol moiety can exist in at least three
      chemical states, the simple thiol, and two altered states. One of the altered
      states displays reactivity toward thiols like dithiothreitol and 2
      mercaptoethanol as well as reagents: mixed disulfides (methanethiosulfonate
      reagents: MTSET+, MTSES-) and an alkylating agent (iodoacetamide). The other
      altered state is unreactive. The phenotype associated with the reactive, altered
      state could be replicated by exposing oocytes expressing T338C CFTR to CuCl2, but
      not by glutathionylation or nitrosylation of the thiol or by oxidation with
      hydrogen peroxide. The results are consistent with the hypothesis that
      substituting a cysteine at 338 can create an adventitious metal binding site.
      Metal liganding alters thiol reactivity and may, in some cases, catalyze
      oxidation of the thiol to an unreactive form such as a sulfinic or sulfonic acid.

PMID- 16436376
TI  - An aurora kinase homologue is involved in regulating both mitosis and cytokinesis
      in Trypanosoma brucei.
AB  - The chromosomal passenger protein aurora kinases have been implicated in
      regulating chromosome segregation and cell division. Three aurora kinase
      homologues were identified (TbAUK1, -2 and -3) in the Trypanosome Genomic Data
      Base, and their expressions in the procyclic form of Trypanosoma brucei were
      knocked down individually by using the RNA interference technique. Only a
      knockdown of TbAUK1 arrested the cells in G(2)/M phase with each cell showing an
      extended posterior end, two kinetoplasts, and an enlarged nucleus, apparently the
      result of an inhibited kinetoplast multiplication and a failed mitosis. There is
      no mitotic spindle structure in the TbAUK1-depleted cell. The two kinetoplasts
      moved apart from each other but stopped just before cytokinesis, suggesting that
      cytokinesis was blocked in its early phase. Overexpression of TbAUK1 in the cells
      resulted in little change in cell growth. By immunofluorescence, TbAUK1 was
      primarily localized to the nucleus in interphase and to the mitotic spindle
      during apparent metaphase and anaphase. Thus, differing from other eukaryotes,
      TbAUK1 has an apparent triple function in coupling mitosis and kinetoplast
      replication with cytokinesis in T. brucei. T. brucei polo-like kinase, previously
      identified as the initiator of cytokinesis without apparent involvement in
      mitosis in the trypanosome, was either depleted or overexpressed in the TbAUK1
      deficient cells. A dominant TbAUK1-depleted phenotype was demonstrated in both
      cases, suggesting that TbAUK1 plays an essential role in cytokinesis that cannot
      be affected by changes in the level of T. brucei polo-like kinase. To our
      knowledge, this is the first time that the function of an aurora B-like kinase is
      a prerequisite for polo-like kinase action in initiating cytokinesis. TbAUK1 is
      also the first identified protein that couples both mitosis and kinetoplast
      replication with cytokinesis in the trypanosome.

PMID- 16436377
TI  - Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase.
AB  - Pyruvate dehydrogenase (PDH), the first component of the human pyruvate
      dehydrogenase complex, has two isoenzymes, somatic cell-specific PDH1 and testis
      specific PDH2 with 87% sequence identity in the alpha subunit of alpha(2) beta(2)
      PDH. The presence of functional testis-specific PDH2 is important for sperm cells
      generating nearly all their energy from carbohydrates via pyruvate oxidation.
      Kinetic and regulatory properties of recombinant human PDH2 and PDH1 were
      compared in this study. Site-specific phosphorylation/dephosphorylation of the
      three phosphorylation sites by four PDH kinases (PDK1-4) and two PDH phosphatases
      (PDP1-2) were investigated by substituting serines with alanine or glutamate in
      PDHs. PDH2 was found to be very similar to PDH1 as follows: (i) in specific
      activities and kinetic parameters as determined by the pyruvate dehydrogenase
      complex assay; (ii) in thermostability at 37 degrees C; (iii) in the mechanism of
      inactivation by phosphorylation of three sites; and (iv) in the phosphorylation
      of sites 1 and 2 by PDK3. In contrast, the differences for PDH2 were indicated as
      follows: (i) by a 2.4-fold increase in binding affinity for the PDH-binding
      domain of dihydrolipoamide acetyltransferase as measured by surface plasmon
      resonance; (ii) by possible involvement of Ser-264 (site 1) of PDH2 in catalysis
      as evident by its kinetic behavior; and (iii) by the lower activities of PDK1,
      PDK2, and PDK4 as well as PDP1 and PDP2 toward PDH2. These differences between
      PDH2 and PDH1 are less than expected from substitution of 47 amino acids in each
      PDH2 alpha subunit. The multiple substitutions may have compensated for any
      drastic alterations in PDH2 structure thereby preserving its kinetic and
      regulatory characteristics largely similar to that of PDH1.

PMID- 16436378
TI  - Nucleoprotein interactions governing cell type-dependent repression of the mouse
      smooth muscle alpha-actin promoter by single-stranded DNA-binding proteins Pur
      alpha and Pur beta.
AB  - Pur alpha and Pur beta are structurally related single-stranded DNA/RNA-binding
      proteins implicated in the control of cell growth and differentiation. The goal
      of this study was to determine whether Pur alpha and Pur beta function in a
      redundant, distinct, or collaborative manner to suppress smooth muscle alpha
      actin gene expression in cell types relevant to wound repair and vascular
      remodeling. RNA interference-mediated loss-of-function analyses revealed that,
      although Pur beta was the dominant repressor, the combined action of endogenous
      Pur alpha and Pur beta was necessary to fully repress the full-length smooth
      muscle alpha-actin promoter in cultured fibroblasts but to a lesser extent in
      vascular smooth muscle cells. The activity of a minimal core enhancer containing
      a truncated 5' Pur repressor binding site was unaffected by knockdown of Pur
      alpha and/or Pur beta in fibroblasts. Conversely, gain-of-function studies
      indicated that Pur alpha or Pur beta could each independently repress core smooth
      muscle alpha-actin enhancer activity albeit in a cell type-dependent fashion.
      Biochemical analyses indicated that purified recombinant Pur alpha and Pur beta
      were essentially identical in terms of their binding affinity and specificity for
      GGN repeat-containing strands of several cis-elements comprising the core
      enhancer. However, Pur alpha and Pur beta exhibited more distinctive protein
      interaction profiles when evaluated for binding to enhancer-associated
      transcription factors in extracts from fibroblasts and vascular smooth muscle
      cells. These findings support the hypothesis that Pur alpha and Pur beta repress
      smooth muscle alpha-actin gene transcription by means of DNA strand-selective cis
      element binding and cell type-dependent protein-protein interactions.

PMID- 16436379
TI  - Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic
      proteins Bax and Bak, leading to cytochrome c release and cell death, independent
      of vacuolation.
AB  - Helicobacter pylori vacuolating cytotoxin, VacA, which causes vacuolation of
      gastric epithelial cells and other types of cultured cells, is known to stimulate
      apoptosis via a mitochondria-dependent pathway. In the present study, we examined
      the mechanisms of VacA-induced mitochondrial damage. Intracellular VacA
      localization was monitored by immunostaining and confocal microscopy; in AZ-521
      cells in which cytochrome c release was stimulated, most of VacA was localized to
      vacuoles rather than mitochondria. VacA reduced the membrane potential of
      isolated mitochondria without inducing cytochrome c release, suggesting that it
      did not act directly to induce cytochrome c release from mitochondria and that in
      intact cells, VacA-induced cytochrome c release involved apoptosis-related
      factor(s), such as a proapoptotic Bcl-2 family protein. In agreement, flow cyto
      metric analyses using antibodies specific for activated Bax revealed that
      intracellular Bax was activated by VacA in a concentration- and time-dependent
      manner. Using active form-specific antibodies, we also observed that the Bcl-2
      family protein, Bak, was activated. By confocal microscopy, Bax and Bak were
      activated in AZ-521 cells in which cyto-chrome c release was induced by VacA. In
      addition, small interfering RNA-induced silencing of the bax gene resulted in
      reduction of VacA-stimulated cytochrome c release, consistent with a contribution
      of VacA-induced Bax activation to cytochrome c release. NH4Cl enhanced both VacA
      induced vacuolation and Bax activation, whereas Bax activation was not inhibited
      by bafilomycin A1, which inhibited vacuolation caused by VacA. These results
      suggest that VacA acts through different signaling pathways to induce apoptosis
      via Bax activation, independent of vacuolation.

PMID- 16436380
TI  - TRAF6 regulates cell fate decisions by inducing caspase 8-dependent apoptosis and
      the activation of NF-kappaB.
AB  - Tumor necrosis factor receptor-associated factor 6 (TRAF6) functions as an
      adaptor, positively regulating the NF-kappaB pathway. Here we report a new
      function of human TRAF6, the direct stimulation of apoptosis. The mechanism of
      apoptosis induction results from the capacity of human TRAF6 to interact and
      activate caspase 8. Both the C-terminal TRAF domain of human TRAF6, which
      directly interacts with the death effector domain of pro-caspase 8, and the N
      terminal RING domain, which is required for activation of caspase 8, are
      necessary for the induction of apoptosis. The role of endogenous TRAF6 in
      regulating apoptosis was confirmed by extinguishing TRAF6 expression with
      specific small-hairpin RNA that resulted in diminished spontaneous apoptosis and
      resistance to induced apoptosis. In contrast to the human molecule, murine TRAF6
      displayed less ability to induce apoptosis and a greater capacity to stimulate NF
      kappaB activity. Human and murine TRAF6 are similar except in the region between
      zinc finger 5 and the TRAF domains. Reciprocal transfer of this connecting region
      completely exchanged the ability of human and murine TRAF6 to induce apoptosis
      and activate NF-kappaB. Unique regions of TRAF6 therefore play an important role
      in determining cell fate.

PMID- 16436381
TI  - p19ras interacts with and activates p73 by involving the MDM2 protein.
AB  - p73beta is a structural and functional homologue of p53, a tumor suppressor gene.
      In this study, we identified a novel p73beta-binding protein, p19ras, by the
      yeast two-hybrid screening method. Alternative splicing of the proto-oncogene H
      ras pre-mRNA has led to two distinct transcripts, p19ras and p21ras. In both
      endogenous and overexpressed systems, we confirmed that p19ras binds to full
      length p73beta in vivo and in vitro. Coexpression of p19ras with p73beta
      stimulated the transcriptional activity of p73beta. Ras proteins are known to be
      small membrane-localized guanine nucleotide-binding proteins. However, unlike
      other Ras proteins, p19ras is localized in the nucleus and the cytosol and its
      interaction with p73beta occurred exclusively in the nucleus. Oncogenic MDM2
      (mouse double minutes 2) is a known repressor of p73 transcriptional activity. In
      this study, when p19ras was bound to MDM2, it further inhibited the association
      of MDM2 to the p73beta protein. In addition, p19ras abolished MDM2-mediated
      transcriptional repression of p73beta. Therefore, this study presents a novel
      pathway of Ras signaling that occurs in the nucleus, involving p19ras and
      p73beta. Furthermore, a p19ras-mediated novel regulatory mechanism of p73
      involving the MDM2 protein is described.

PMID- 16436383
TI  - Subcellular localization and membrane topology of the Dengue virus type 2 Non
      structural protein 4B.
AB  - Dengue virus (DV) is a member of the family Flaviviridae. These positive strand
      RNA viruses encode a polyprotein that is processed in case of DV into 10
      proteins. Although for most of these proteins distinct functions have been
      defined, this is less clear for the highly hydrophobic non-structural protein
      (NS) 4B. Despite its possible role as an antagonist of the interferon-induced
      antiviral response, this protein may play an additional more direct role for
      viral replication. In this study we determined the subcellular localization,
      membrane association, and membrane topology of DV NS4B. We found that NS4B
      resides primarily in cytoplasmic foci originating from the endoplasmic reticulum.
      NS4B colocalizes with NS3 and double-stranded RNA, an intermediate of viral
      replication, arguing that NS4B is part of the membrane-bound viral replication
      complex. Biochemical analysis revealed that NS4B is an integral membrane protein,
      and that its preceding 2K signal sequence is not required for this integration.
      We identified three membrane-spanning segments in the COOH-terminal part of NS4B
      that are sufficient to target a cytosolic marker protein to intracellular
      membranes. Furthermore, we established a membrane topology model of NS4B in which
      the NH2-terminal part of the protein is localized in the endoplasmic reticulum
      lumen, whereas the COOH-terminal part is composed of three trans-membrane domains
      with the COOH-terminal tail localized in the cytoplasm. This topology model
      provides a good starting point for a detailed investigation of the function of
      NS4B in the DV life cycle.

PMID- 16436382
TI  - TRPM7 regulates cell adhesion by controlling the calcium-dependent protease
      calpain.
AB  - m-Calpain is a protease implicated in the control of cell adhesion through focal
      adhesion disassembly. The mechanism by which the enzyme is spatially and
      temporally controlled is not well understood, particularly because the dependence
      of calpain on calcium exceeds the submicromolar concentrations normally observed
      in cells. Here we show that the channel kinase TRPM7 localizes to peripheral
      adhesion complexes with m-calpain, where it regulates cell adhesion by
      controlling the activity of the protease. Our research revealed that
      overexpression of TRPM7 in cells caused cell rounding with a concomitant loss of
      cell adhesion that is dependent upon the channel of the protein but not its
      kinase activities. Knockdown of m-calpain blocked TRPM7-induced cell rounding and
      cell detachment. Silencing of TRPM7 by RNA interference, however, strengthened
      cell adhesion and increased the number of peripheral adhesion complexes in the
      cells. Together, our results suggest that the ion channel TRPM7 regulates cell
      adhesion through m-calpain by mediating the local influx of calcium into
      peripheral adhesion complexes.

PMID- 16436384
TI  - Self-association and chaperone activity of Hsp27 are thermally activated.
AB  - The small heat shock protein 27 (Hsp27) is an oligomeric, molecular chaperone in
      vitro. This chaperone activity and other physiological roles attributed to Hsp27
      have been reported to depend on the state of self-association. In the present
      work, we have used sedimentation velocity experiments to demonstrate that the
      self-association of Hsp27 is independent of pH and ionic strength but increases
      significantly as the temperature is increased from 10 to 40 degrees C. The
      largest oligomers formed at 10 degrees C are approximately 8-12 mer, whereas at
      40 degrees C oligomers as large as 22-30 mer are observed. Similarly, the
      chaperone activity of Hsp27 as indicated by its ability to inhibit dithiothreitol
      induced insulin aggregation also increases with increased temperature, with a
      particularly sharp increase in activity as temperature is increased from 34 to 43
      degrees C. Similar studies of an Hsp27 triple variant that mimics the behavior of
      the phosphorylated protein establish that this protein has greatly diminished
      chaperone activity that responds minimally to increased temperature. We conclude
      that Hsp27 can exploit a large number of oligomerization states and that the
      range of oligomer size and the magnitude of chaperone activity increase
      significantly as temperature is increased over the range that is relevant to the
      physiological heat shock response.

PMID- 16436385
TI  - Role for Akt/protein kinase B and activator protein-1 in cellular proliferation
      induced by the human T-cell leukemia virus type 1 tax oncoprotein.
AB  - Human T-cell leukemia virus type 1 is an oncogenic retrovirus etiologically
      causal of adult T-cell leukemia. The virus encodes a Tax oncoprotein, which
      functions in transcriptional regulation, cell cycle control, and transformation.
      Because adult T-cell leukemia is a highly virulent cancer that is resistant to
      numerous chemotherapeutic treatments, to understand better this disease it is
      important to comprehend how human T-cell leukemia virus type 1 promotes cellular
      growth and survival. Most of the existing data point to Tax activation of NF
      kappaB as important for cellular proliferation and transformation. We show here
      that Tax, in the absence of NF-kappaB signaling, can activate activator protein-1
      to promote cellular proliferation and survival. Tax is shown to activate
      activator protein-1 through the phosphatidylinositol 3-kinase/Akt pathway.

PMID- 16436386
TI  - Crystallographic evidence that the dinuclear copper center of tyrosinase is
      flexible during catalysis.
AB  - At high resolution, we determined the crystal structures of copper-bound and
      metal-free tyrosinase in a complex with ORF378 designated as a "caddie" protein
      because it assists with transportation of two CuII ions into the tyrosinase
      catalytic center. These structures suggest that the caddie protein covers the
      hydrophobic molecular surface of tyrosinase and interferes with the binding of a
      substrate tyrosine to the catalytic site of tyrosinase. The caddie protein, which
      consists of one six-strandedbeta-sheet and one alpha-helix, has no similarity
      with all proteins deposited into the Protein Data Bank. Although tyrosinase and
      catechol oxidase are classified into the type 3 copper protein family, the latter
      enzyme lacks monooxygenase activity. The difference in catalytic activity is
      based on the structural observations that a large vacant space is present just
      above the active center of tyrosinase and that one of the six His ligands for the
      two copper ions is highly flexible. These structural characteristics of
      tyrosinase suggest that, in the reaction that catalyzes the ortho-hydroxylation
      of monophenol, one of the two Cu(II) ions is coordinated by the peroxide
      originated oxygen bound to the substrate. Our crystallographic study shows
      evidence that the tyrosinase active center formed by dinuclear coppers is
      flexible during catalysis.

PMID- 16436387
TI  - The anti-angiogenic His/Pro-rich fragment of histidine-rich glycoprotein binds to
      endothelial cell heparan sulfate in a Zn2+-dependent manner.
AB  - The plasma protein histidine-rich glycoprotein (HRGP), which has been identified
      as an angiogenesis inhibitor, binds to heparan sulfate (HS) in a Zn(2+)-dependent
      manner. We wished to test whether this interaction is mechanistically important
      in mediation of the anti-angiogenic effect of HRGP. Inhibition of angiogenesis by
      HRGP is exerted through its central His/Pro-rich domain, which is proteolytically
      released. A 35-amino-acid residue synthetic peptide, HRGP330, derived from the
      His/Pro-rich domain retains the inhibitory effect on blood vessel formation in
      vitro and in vivo, an effect dependent on the presence of Zn(2+). We now show
      that HRGP330 binds heparin/HS with the same capacity as full-length HRGP, and the
      binding is Zn(2+)-dependent. Peptides derived from the His/Pro-rich domain of
      HRGP downstream of HRGP330 fail to inhibit endothelial cell migration and display
      a significantly reduced heparin-binding capacity. An even shorter peptide,
      HRGP335, covering a 26-amino-acid sequence within HRGP330 retains full heparin/HS
      binding capacity. Characterization of the HS interaction shows that there is a
      tissue-specific HS pattern recognized by HRGP335 and that the minimal length of
      heparin/HS required for binding to HRGP335 is an 8-mer oligosaccharide.
      Saturation of the HS binding sites in HRGP330 by pre-incubation with heparin
      abrogates the HRGP330-induced rearrangement of endothelial cell focal adhesions,
      suggesting that interaction with cell surface HS is needed for HRGP330 to exert
      its anti-angiogenic effect.

PMID- 16436388
TI  - Regulation of fibroblast growth factor-23 signaling by klotho.
AB  - The aging suppressor gene Klotho encodes a single-pass transmembrane protein.
      Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which
      are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient
      mice. To test the possibility that Klotho and FGF23 may function in a common
      signal transduction pathway(s), we investigated whether Klotho is involved in FGF
      signaling. Here we show that Klotho protein directly binds to multiple FGF
      receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity
      than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability
      of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various
      types of cells. Thus, Klotho functions as a cofactor essential for activation of
      FGF signaling by FGF23.

PMID- 16436389
TI  - The time for tobacco industry sponsored PREP evaluation has arrived.

PMID- 16436390
TI  - Iraq: an important start in the Kurdish region.

PMID- 16436391
TI  - Sweden: ads snuffed out.

PMID- 16436392
TI  - Pakistan: health warnings, industry-style.

PMID- 16436394
TI  - Thailand: mass exercise, petition, and lure-free points of sale.

PMID- 16436396
TI  - Hong Kong, China: Marlboro pack sleeves.

PMID- 16436397
TI  - A randomised control study of a fully automated internet based smoking cessation
      programme.
AB  - OBJECTIVE: The objective of this project was to test the short term (90 days)
      efficacy of an automated behavioural intervention for smoking cessation, the "1-2
      3 Smokefree" programme, delivered via an internet website. DESIGN: Randomised
      control trial. Subjects surveyed at baseline, immediately post-intervention, and
      90 days later. SETTINGS: The study and the intervention occurred entirely via the
      internet site. Subjects were recruited primarily via worksites, which referred
      potential subjects to the website. SUBJECTS: The 351 qualifying subjects were
      notified of the study via their worksite and required to have internet access.
      Additionally, subjects were required to be over 18 years of age, smoke
      cigarettes, and be interested in quitting smoking in the next 30 days. Eligible
      subjects were randomly assigned individually to treatment or control condition by
      computer algorithm. INTERVENTION: The intervention consisted of a video based
      internet site that presented current strategies for smoking cessation and
      motivational materials tailored to the user's race/ethnicity, sex, and age.
      Control subjects received nothing for 90 days and were then allowed access to the
      programme. MAIN OUTCOME MEASURES: The primary outcome measure was abstinence from
      smoking at 90 day follow up. RESULTS: At follow up, the cessation rate at 90 days
      was 24.1% (n = 21) for the treatment group and 8.2% (n = 9) for the control group
      (p = 0.002). Using an intent-to-treat model, 12.3% (n = 21) of the treatment
      group were abstinent, compared to 5.0% (n = 9) in the control group (p = 0.015).
      CONCLUSIONS: These evaluation results suggest that a smoking cessation programme,
      with at least short term efficacy, can be successfully delivered via the
      internet.

PMID- 16436399
TI  - 22 years on: the impact and relevance of the UK No Smoking Day.
AB  - OBJECTIVES: To evaluate the impact and relevance of the national awareness day
      "No Smoking Day" 22 years after it was launched. DESIGN: Triangulation of data
      from a variety of sources. Retrospective surveys conducted one week and three
      months after No Smoking Day, media coverage, website activity, and volume of
      calls to national smokers' helplines. MAIN OUTCOME MEASURES: Self reports of
      awareness and smoking behaviour changes one week and three months after No
      Smoking Day. Volume of media coverage, visits to No Smoking Day website, and
      volumes of calls to smokers' helplines. RESULTS: Follow up at one week indicates
      awareness of No Smoking Day is lower in 2004 than in 1986 but still high at 70%
      for all smokers. The decline in participation from 18% of aware smokers in 1994
      to 7% in 2001 has been reversed and in 2005 19% quit or reduced their smoking on
      No Smoking Day. Three months after No Smoking Day awareness was 78% in 2004,
      lower than in previous studies but still high and equivalent to 9,965,000 smokers
      when applied to the population estimate of UK smokers. Likewise participation has
      decreased but at 14% in 2004 is equivalent to an estimated 1,840,000 (1 in 7 of
      UK smokers) claiming to quit or reduce their consumption on the Day. Among those
      who participated, 11% were still not smoking more than three months after the
      Day, equivalent to an estimated 85,000 smokers (0.7% of UK smokers). Media volume
      has increased even though campaign spend has remained relatively constant and
      calls to national smokers' helplines on No Smoking Day are typically four times
      those received on an average day. CONCLUSIONS: These data suggest that after 22
      years No Smoking Day continues to be successful in reaching smokers. With a
      budget insufficient to pay for advertising, this public awareness campaign
      supported by local activities appears to be effective in helping smokers to stop.

PMID- 16436398
TI  - Industry sponsored anti-smoking ads and adolescent reactance: test of a boomerang
      effect.
AB  - OBJECTIVE: To examine whether adolescents' exposure to youth smoking prevention
      ads sponsored by tobacco companies promotes intentions to smoke, curiosity about
      smoking, and positive attitudes toward the tobacco industry. DESIGN: A randomised
      controlled experiment compared adolescents' responses to five smoking prevention
      ads sponsored by a tobacco company (Philip Morris or Lorillard), or to five
      smoking prevention ads sponsored by a non-profit organisation (the American
      Legacy Foundation), or to five ads about preventing drunk driving. SETTING: A
      large public high school in California's central valley. SUBJECTS: A convenience
      sample of 9th and 10th graders (n = 832) ages 14-17 years. MAIN OUTCOME MEASURES:
      Perceptions of ad effectiveness, intention to smoke, and attitudes toward tobacco
      companies measured immediately after exposure. RESULTS: As predicted, adolescents
      rated Philip Morris and Lorillard ads less favourably than the other youth
      smoking prevention ads. Adolescents' intention to smoke did not differ as a
      function of ad exposure. However, exposure to Philip Morris and Lorillard ads
      engendered more favourable attitudes toward tobacco companies. CONCLUSIONS: This
      study demonstrates that industry sponsored anti-smoking ads do more to promote
      corporate image than to prevent youth smoking. By cultivating public opinion that
      is more sympathetic toward tobacco companies, the effect of such advertising is
      likely to be more harmful than helpful to youth.

PMID- 16436400
TI  - Are comprehensive environmental changes as effective as health education for
      smoking cessation?
AB  - OBJECTIVES: To compare the effectiveness of health education on smoking cessation
      for all smokers regardless of their willingness to quit smoking and cumulative
      environmental changes including designation of smoking places, legislation, and
      price rise. DESIGN: Comparison of smoking cessation rates over two time periods:
      the period of health education on smoking cessation (1997-1999), and the period
      of cumulative environmental changes (2002-2004). SETTING: An occupational setting
      in a radiator manufacturing factory in Japan. SUBJECTS: All habitual male smokers
      who remained in the worksite through the pertinent time period (n = 202 in the
      period of health education and n = 170 in the period of environmental changes).
      MAIN OUTCOME MEASUREMENTS: Smoking cessation rates at the end of each time
      period. RESULTS: The smoking cessation rates over the periods of health education
      and environmental changes were 8.9% and 7.1%, respectively. There was no
      difference between these two proportions in a chi2 test (p = 0.513). The age
      adjustment did not significantly alter the cessation rate. CONCLUSIONS:
      Cumulative environmental changes are fairly effective in promoting smoking
      cessation, and may yield similar smoking cessation rates as a health education
      intervention reaching all smokers regardless of their willingness to quit
      smoking.

PMID- 16436401
TI  - Medicaid reimbursement for prenatal smoking intervention influences quitting and
      cessation.
AB  - BACKGROUND: 40% of births in the USA are covered by Medicaid and smoking is
      prevalent among recipients. The objective of this study was to evaluate the
      association between levels of Medicaid coverage for prenatal smoking cessation
      interventions on quitting during pregnancy and maintaining cessation after
      delivery. METHODS: Population based survey study of 7513 post-partum women from
      15 states who: participated in Pregnancy Risk Assessment Monitoring System
      (PRAMS) during 1998-2000; smoked at the beginning of their pregnancy; and had
      Medicaid coverage. Participating states were categorised into three levels of
      Medicaid coverage for smoking cessation interventions during prenatal care:
      extensive (pharmacotherapies and counselling); some (pharmacotherapies or
      counselling); or none. Quit rates among women who smoked before pregnancy and
      rates of maintaining cessation were examined. RESULTS: Higher levels of coverage
      during prenatal care for smoking cessation interventions were associated with
      higher quit rates; 51%, 43%, and 39% of women quit in states with extensive,
      some, and no coverage, respectively. Compared to women in states with no
      coverage, women in states with extensive coverage had 1.6 times the odds of
      quitting smoking (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.00 to
      2.49). Maintenance of cessation after delivery was associated with extensive
      levels of Medicaid coverage; 48% of women maintained cessation in states with
      extensive coverage compared to 37% of women in states with no coverage. Compared
      to women in states with no coverage, women with extensive coverage had 1.6 times
      the odds of maintaining cessation (OR 1.63, 95% CI 1.04 to 2.56). CONCLUSIONS:
      Prenatal Medicaid coverage for both pharmacotherapies and counselling is
      associated with higher rates of quitting and continued cessation. This suggests
      policymakers can promote cessation by broadening smoking cessation services in
      Medicaid prenatal coverage.

PMID- 16436403
TI  - Tobacco sales in pharmacies: time to quit.
AB  - OBJECTIVE: To assess the pharmacy profession's perceptions of tobacco sales in US
      pharmacies and explore whether a policy prohibiting sales of tobacco in
      pharmacies would alter adult consumer shopping behaviour. SUBJECTS AND DESIGN: In
      California, surveys were administered to 1168 licensed pharmacists and 1518
      pharmacy students, and telephone interviews were conducted with 988 adult
      consumers. RESULTS: Most (58.1%) licensed pharmacists were strongly against sales
      of tobacco in pharmacies, 23.6% were against it, 16.7% were neutral, 1.2% were in
      favour of it, and 0.4% were strongly in favour of it. Pharmacists who were
      current tobacco users were more likely to be in favour of tobacco sales in
      pharmacies than were pharmacists who were current non-users (p < 0.005). Similar
      statistics were observed for pharmacy students. Most consumers (72.3%) disagreed
      with the statement, "I am in favour of tobacco products being sold in
      drugstores"; 82.6% stated that if the drugstore where they most commonly shopped
      were to stop selling tobacco products, they would shop there just as often, 14.2%
      would shop there more often, and 3.2% would shop there less often. CONCLUSION:
      Little professional or public support exists for tobacco sales in pharmacies.

PMID- 16436405
TI  - Smokers' reactions to reduced ignition propensity cigarettes.
AB  - BACKGROUND: On 28 June 2004, New York State (NY) became the first jurisdiction to
      require cigarettes to meet a reduced ignition propensity (RIP) standard. This law
      resulted in cigarette manufacturers modifying nearly all of their brands sold in
      NY. However, the same cigarette brands sold in other states were not modified to
      meet the RIP standard. OBJECTIVES: This paper examines relationships between the
      RIP law and smokers' awareness of changes in the performance of their cigarettes
      (that is, going out more frequently, change in taste), and smoking behaviour.
      METHODS: Data for this analysis come from a nationwide survey of 2088 adult
      smokers (> 18 years of age) conducted in the USA between July and December 2004.
      143 of the smokers included in the survey were residents of NY while the
      remainder were from other states (n = 1945). Survey participants were asked
      whether their cigarettes "ever go out between puffs" and whether they had noticed
      any change in the taste of their cigarettes in the past 12 months. RESULTS: NY
      smokers were three times more likely than smokers in other states to report that
      their cigarettes often went out between puffs (17.3% v 5.6%). However, NY smokers
      appeared no more likely to report noticing differences in cigarette taste, an
      intention to quit smoking, or to have made quit attempts. CONCLUSIONS: A
      significant minority of smokers in NY reported noticing changes in the
      performance of their cigarettes following the RIP law, as would be expected.
      However, the RIP law appears to have had no impact on the smoking habits of New
      Yorkers, countering arguments made by cigarette manufacturers that the law would
      impact consumer acceptability.

PMID- 16436404
TI  - New tobacco products: do smokers like them?
AB  - BACKGROUND: There is little information about smokers who tried potentially
      reduced exposure products (PREPs) (Eclipse, Omni, Advance Lights, Accord, or
      Ariva), why they tried them, if they liked these products, and if they will
      continue to use them. OBJECTIVES: The objectives of this qualitative study were
      to understand: (1) how smokers who tried PREPs learned about them, (2) reasons
      for first trying PREPs, (3) which PREP(s) they tried, (4) what they thought of
      the product at first trial, (5) reasons for continuing or discontinuing use, and
      (6) whether they would recommend PREPs to others. DESIGN: In October 2002, 16
      focus group sessions were conducted with current cigarette smokers aged 30-50
      years: eight groups in Chattanooga, Tennessee, and eight in Dallas, Texas.
      Specific focus groups were composed of white men, white women, African American
      men, African American women, Hispanic men, or Hispanic women. RESULTS: The
      majority of the participants learned about PREPs through advertising or
      promotion, family, friends, and co-workers; major reasons given for first trying
      PREPs were that the products were free or inexpensive, they wanted to stop
      smoking, they believed the product claims of fewer health risks, or they were
      curious; most of them tried Eclipse probably because the focus groups were
      conducted in the same cities where Eclipse was introduced; most participants did
      not like PREPs; most discontinued the use of PREPS, some who continued to use
      them did so infrequently and also kept smoking their regular brands of
      cigarettes; and most would not recommend PREPs, although a few might recommend
      them to specific groups (for example, new smokers, the young, women, curious or
      health conscious people). CONCLUSIONS: Although most established smokers did not
      like the PREPs they tried and will not recommend them to anyone, a minority of
      established smokers believe that there may be a market for these products.

PMID- 16436406
TI  - Tobacco industry litigation strategies to oppose tobacco control media campaigns.
AB  - OBJECTIVE: To document the tobacco industry's litigation strategy to impede
      tobacco control media campaigns. METHODS: Data were collected from news and
      reports, tobacco industry documents, and interviews with health advocates and
      media campaign staff. RESULTS: RJ Reynolds and Lorillard attempted to halt
      California's Media Campaign alleging that the campaign polluted jury pools and
      violated First Amendment rights because they were compelled to pay for anti
      industry ads. The American Legacy Foundation was accused of violating the Master
      Settlement Agreement's vilification clause because its ads attacked the tobacco
      industry. The tobacco companies lost these legal challenges. CONCLUSION: The
      tobacco industry has expanded its efforts to oppose tobacco control media
      campaigns through litigation strategies. While litigation is a part of tobacco
      industry business, it imposes a financial burden and impediment to media
      campaigns' productivity. Tobacco control professionals need to anticipate these
      challenges and be prepared to defend against them.

PMID- 16436407
TI  - The social context of smoking: the next frontier in tobacco control?
AB  - A better understanding of the social context of smoking may help to enhance
      tobacco control research and practice.

PMID- 16436409
TI  - Smoke-free law did affect revenue from gaming in Delaware.

PMID- 16436408
TI  - Levels of toxins in oral tobacco products in the UK.
AB  - OBJECTIVE: This study examined the constituents of smokeless tobacco products
      available in the UK and compared them with products available in India, Sweden,
      and the USA. METHODS: Seven UK brands of smokeless tobacco, including a tooth
      cleaning powder, and four international brands of smokeless tobacco were tested
      for a range of toxins and known carcinogens, such as tobacco specific N
      nitrosamines (TSNA), as well as nicotine availability. RESULTS: Ten of the 11
      brands tested had detectable levels of tobacco specific nitrosamines, which are
      proven carcinogens, and levels varied 130-fold. All had detectable levels of
      benzo(a)pyrene, another proven carcinogen (with around 175-fold variation) and
      several toxic metals (with nearly 150-fold variation). Nicotine availability
      varied in the UK products from 0.1 mg/g to 63.2 mg/g. All the tobacco products
      tested are likely to be hazardous to users' health, but the data indicate that it
      should be possible to reduce key toxins to non-detectable levels. CONCLUSIONS:
      Smokeless tobacco products should be regulated and standards set for maximum
      levels of toxins and carcinogens.

PMID- 16436410
TI  - Health meetings do not belong in smoky cities.

PMID- 16436412
TI  - Seasonal variations in stage of change among Quitline clients.

PMID- 16436413
TI  - Health consequences of smoking 1-4 cigarettes per day: response to G F Cope
      (eletter to journal).

PMID- 16436414
TI  - Is there public support for banning smoking in motor vehicles?

PMID- 16436415
TI  - The pneumococcus: 'old man's friend' and children's foe.

PMID- 16436416
TI  - Innate immunity and the pneumococcus.
AB  - The innate immune system provides a non-specific first line of defence against
      microbes and is crucial both in the development and effector stages of subsequent
      adaptive immune responses. Consistent with its importance, study of the innate
      immune system is a broad and fast-moving field. Here we provide an overview of
      the recent key advances made in this area with relation to the important pathogen
      Streptococcus pneumoniae (the pneumococcus).

PMID- 16436417
TI  - Versatility of pneumococcal surface proteins.
AB  - Surface-exposed proteins are key players during the infectious process of
      pathogenic bacteria. The cell surface of the Gram-positive human pathogen
      Streptococcus pneumoniae is decorated not only by typical Gram-positive surface
      proteins, but also by a family of proteins that recognizes the phosphorylcholine
      of the lipoteichoic and teichoic acids, namely the choline-binding proteins, and
      by non-classical surface proteins that lack a leader peptide and membrane-anchor
      motif. A comprehensive understanding of how microbial proteins subvert host
      immunity or host protein functions is a prerequisite for the development of novel
      therapeutic strategies to combat pneumococcal infections. This article reviews
      recent progress in the investigation of the versatility and sophistication of the
      virulence functions of surface-exposed pneumococcal proteins.

PMID- 16436418
TI  - Differential expression of key pneumococcal virulence genes in vivo.
AB  - Few studies have examined in vivo virulence gene expression in Streptococcus
      pneumoniae. In this study, expression of key pneumococcal virulence genes cbpA,
      pspA, ply, psaA, cps2A, piaA, nanA and spxB in the nasopharynx, lungs and
      bloodstream of mice was investigated, following intranasal challenge with the
      serotype 2 strain D39. Bacterial RNA was extracted, linearly amplified and
      assayed by real-time RT-PCR. At 72 h, cbpA mRNA was present at higher levels in
      the nasopharynx and lungs than in the blood. At this time-point, the mRNAs for
      PspA and PiaA were most abundant in the nasopharynx, whereas no significant
      difference in gene expression between niches was observed for ply, psaA and
      cps2A. Both nanA and spxB mRNAs were present in higher amounts in the nasopharynx
      than in the lungs or blood. These findings illustrate the dynamic nature of
      pneumococcal virulence gene expression in vivo.

PMID- 16436419
TI  - Zinc metalloproteinase genes in clinical isolates of Streptococcus pneumoniae:
      association of the full array with a clonal cluster comprising serotypes 8 and
      11A.
AB  - Pneumococci display large zinc metalloproteinases on the surface, including the
      IgA protease, which cleaves human IgA1 in the hinge region, the ZmpC proteinase,
      which cleaves human matrix metalloproteinase 9 (MMP-9), and two other
      proteinases, ZmpB and ZmpD, whose substrates have not yet been identified.
      Surface metalloproteinases are antigenic and have been linked to virulence. The
      genes encoding these proteinases reside in three distinct loci: two loci specific
      for zmpB and zmpC, and a third, the iga locus, containing iga and zmpD. Data
      obtained by this and other groups have shown that pneumococcal metalloproteinase
      genes are transcribed and yield mature and enzymatically active proteins. Since
      the presence of the four proteinase genes is variable in the pneumococcal strains
      whose genomes have been sequenced, the presence of these genes in a collection of
      218 pneumococcal isolates, mostly from invasive disease, was investigated. The
      data showed that zmpB and iga were present in all the isolates examined, while
      zmpC and zmpD were present in a variable proportion of the isolates (in 18 and 49
      %, respectively). Interestingly, isolates carrying both zmpC and zmpD were found
      to belong mainly to two serotypes (sts), 8 and 11A. By molecular typing, st 8 and
      st 11A isolates appeared to belong to the same clonal cluster. The presence of
      these two additional metalloproteinases could contribute to the fitness of
      particular pneumococcal clones.

PMID- 16436420
TI  - Inhibition of competence development in Streptococcus pneumoniae by increased
      basal-level expression of the ComDE two-component regulatory system.
AB  - Natural competence for genetic transformation in Streptococcus pneumoniae is
      controlled by the ComCDE signal-transduction pathway. Together, ComD, a membrane
      histidine kinase, and ComE, its cognate response regulator, constitute a typical
      two-component regulatory system involved in sensing the comC-encoded competence
      stimulating peptide (CSP). The comCDE operon is strongly upregulated when CSP
      reaches a critical threshold, probably to coordinate competence induction
      throughout the population. During a study of the early regulation of the comCDE
      operon, a mutation which resulted in increased beta-galactosidase production from
      a comC : : lacZ fusion was isolated. This mutation, which was characterized as a
      G-->T change in the transcription terminator of the tRNA(Arg) located immediately
      upstream of comCDE, is suggested to destabilize the terminator and to allow
      transcriptional readthrough of comCDE. Here, it is shown that, quite
      unexpectedly, the mutation confers reduced transformability. A series of
      experiments undertaken with the aim of understanding this surprising phenotype is
      described. Evidence is presented that increased basal-level expression of comDE
      impedes both spontaneous and CSP-induced competence in S. pneumoniae. There is a
      discussion of how an increased concentration of ComD and/or ComE could affect
      competence development.

PMID- 16436421
TI  - LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus
      pneumoniae.
AB  - The ubiquitous protein LuxS with S-ribosylhomocysteinase activity is involved in
      S-adenosyl methionine detoxification, C-1 unit recycling and the production of
      autoinducers that allow the cell to sense and respond to cell density.
      Independent reports describe the impact of LuxS deficiency on Streptococcus
      pneumoniae virulence in the mouse. In vitro, LuxS deficiency confers discrete
      phenotypes. A combined approach using genetic dissection and mixed-culture
      experiments allowed the involvement of LuxS in the developmental physiology of S.
      pneumoniae to be investigated. Functional LuxS was found to be related on the one
      hand to down-regulation of competence, and on the other hand to attenuation of
      autolysis in cultures entering stationary phase. The competence phenotype of luxS
      mutant bacteria was complemented by media conditioned by competence-defective
      ComAB0 bacteria, but not by BSA. The autolytic phenotype was complemented by BSA,
      but not by conditioned supernatants. It is suggested that the impact of LuxS on
      competence, but not on autolysis, involves cell-cell communication. The phenotype
      of luxS mutant strains reveals a hierarchy in the competence regulatory networks
      of S. pneumoniae.

PMID- 16436422
TI  - Construction and evaluation of a chromosomal expression platform (CEP) for
      ectopic, maltose-driven gene expression in Streptococcus pneumoniae.
AB  - In this paper, the construction and evaluation of a chromosomal expression
      platform (CEP), which allows controlled gene expression following ectopic
      integration into the chromosome of Streptococcus pneumoniae, is described. CEP is
      based on the well-studied maltosaccharide-inducible system. To facilitate
      integration at CEP, a plasmid, pCEP, capable of replication in Escherichia coli,
      but not in S. pneumoniae, was assembled. This plasmid contains an
      expression/selection cassette flanked on each side by more than 2 kb of
      pneumococcal DNA. The cassette comprises a maltose-inducible promoter, P(M),
      separated from a kanamycin-resistance gene by NcoI and BamHI cloning sites.
      Clones harbouring the gene of interest integrated at CEP under the control of
      P(M) can be obtained through direct transformation of an S. pneumoniae recipient
      with ligation products between that gene and NcoI/BamHI-digested pCEP DNA,
      followed by selection for kanamycin-resistant transformants.

PMID- 16436423
TI  - To have neighbour's fare: extending the molecular toolbox for Streptococcus
      pneumoniae.
AB  - In past years, several useful genetic tools have been developed to study the
      molecular biology of Streptococcus pneumoniae. In order to extend the existing
      spectrum of tools, advantage was taken of the toolbox originally developed for
      the closely related bacterium Lactococcus lactis, which was adapted for the
      manipulation of S. pneumoniae. The modified tools are as follows. (i) An improved
      nisin-inducible (over)expression system (NICE). The nisRK genes, encoding a two
      component system essential for transcriptional activation in response to nisin,
      were integrated into the bgaA locus of S. pneumoniae D39. In this strain,
      D39nisRK, addition of nisin resulted in the overexpression of several genes
      placed under the control of the nisin-inducible promoter, while no detectable
      expression was observed in the absence of nisin. (ii) A lacZ reporter system.
      Using strain D39nisRK, which lacks endogenous beta-galactosidase activity, the
      usefulness of the lacZ reporter vector pORI13 for the generation of chromosomal
      transcriptional fusions was demonstrated. In addition, the repA gene, necessary
      for the replication of pORI13, was introduced into the bgaA locus, thereby
      generating a background for plasmid-based promoter expression studies. (iii) A
      simplified chemically defined medium, which supports growth of all sequenced S.
      pneumoniae strains to a level comparable to that in complex medium. (iv) A system
      for the introduction of unmarked deletions and mutations into the chromosome,
      which is independent of the genotype of the target strain. Most of these systems
      were successfully applied in strains R6 and TIGR4 as well. In addition, the tools
      offer several improvements and advantages compared to existing ones. Thus, the
      molecular toolbox for S. pneumoniae has been successfully extended.

PMID- 16436424
TI  - Distribution of epidemic antibiotic-resistant pneumococcal clones in Scottish
      pneumococcal isolates analysed by multilocus sequence typing.
AB  - Sequence types of pneumococci isolated in Scotland between 1996 and 2003 were
      compared with those of globally prevalent antibiotic-resistant clones. Multilocus
      sequence typing was performed on 252 invasive pneumococcal isolates referred to
      the Scottish Meningococcus and Pneumococcus Reference Laboratory. Isolates were
      not preselected for antimicrobial resistance, patient age or disease caused.
      Sequence types were compared with globally significant antimicrobial-resistant
      clones identified by the Pneumococcal Molecular Epidemiology Network (PMEN).
      Sequence types identical with three of the 26 PMEN clones were present in the
      Scottish collection; the clones were the Spain(9V)-3 clone (sequence type 156,
      seven isolates), the England(14)-9 clone (sequence type 9, eight isolates) and
      the Utah(35B)-24 clone (sequence type 377, one isolate). Many Scottish isolates
      related to PMEN clones had lower antimicrobial MICs than those described for the
      corresponding PMEN type strain. A number of single- (SLVs) and double-locus
      variants (DLVs) were present. Fifteen SLVs related to PMEN sequence types 37, 67,
      90, 81, 156, 236 and 377 were detected. The collection contained 10 DLVs related
      to PMEN sequence types 37, 156, 173 and 338. The majority of SLVs and DLVs were
      penicillin- or erythromycin-sensitive variants of the resistant PMEN type
      strains. Capsule switching in isolates related to the PMEN clones was also
      detected. The highest levels of penicillin resistance were detected in sequence
      type 320 (serotype 19F), which is not a PMEN clone. These data suggest that PMEN
      clones are not widely distributed in disease-causing isolates in Scotland.

PMID- 16436425
TI  - Identification, prevalence and population structure of non-typable Streptococcus
      pneumoniae in carriage samples isolated from preschoolers attending day-care
      centres.
AB  - The authors aimed to get insights into the population structure of non
      (sero)typable pneumococci (NTPn), a specific group of natural atypical
      pneumococci whose identification is often difficult, and which has remained
      insufficiently studied. A total of 265 presumptive NTPn, isolated between 1997
      and 2003 from the nasopharynx of children, were characterized. Strains were
      confirmed to be pneumococci on the basis of bile solubility, and PCR detection or
      Southern blotting hybridization of lytA and psaA, genes ubiquitous in this
      species. Multilocus sequence typing (MLST) was used to exclude two isolates that
      gave ambiguous results. Non-typability was confirmed by the Quellung reaction
      using Omniserum. A total of 213 isolates were considered to be true NTPn. The
      molecular analysis of the true NTPn by PFGE and MLST showed that this population
      was genetically diverse, although a dominant cluster, accounting for 66 % of the
      isolates, was identified. Antimicrobial resistance was observed in most genetic
      backgrounds, and multidrug resistance to penicillin, erythromycin, clindamycin,
      tetracycline and sulfamethoxazole-trimethoprim was associated with strains
      belonging to the dominant cluster. Comparison with PFGE fingerprints and sequence
      types of large collections of serotypable strains showed that the genetic
      backgrounds of all but two NTPn were different from those found in serotypable
      strains. In addition, we found that NTPn strains with similar genetic backgrounds
      to those identified in our study had been isolated from disease sources in other
      countries. These observations seem to indicate that NTPn have diverse genetic
      backgrounds and may have evolved as a distinct group of pneumococcal isolates.

PMID- 16436426
TI  - Dynamics of pneumococcal colonization in healthy Dutch children.
AB  - A recent study of pneumococcal colonization in 3198 healthy children of 1-19
      years of age in The Netherlands showed pneumococcal colonization in 19 % of the
      children, with a peak incidence of 55 % at the age of 2 years; an age-related
      serotype distribution was also found. In the present study, the genetic
      background and resistance profiles of 578 pneumococcal isolates from the latter
      study were characterized by means of chromosomal genotyping and susceptibility
      testing. In contrast to the age-related serotype distribution observed
      previously, the genetic background of the strains was not age related. Few
      strains were found showing close homology (>95 %) with the international clones
      Spain(9V)-3 (ten isolates showed homology), England(14)-9 (four isolates),
      Tennessee(23F)-4 (two isolates), CSR(14)-10 (one isolate) and Sweden(15A)-25 (one
      isolate). In total, 19 % of strains showed resistance to one or more antibiotics.
      Resistance to cotrimoxazole, tetracycline, erythromycin and penicillin was found
      in 12.9, 5.6, 5.0 and 2.7 % of isolates, respectively. Multidrug resistance was
      found in 1.9 % of strains. In conclusion, pneumococcal colonization isolates from
      healthy Dutch children represent a heterogeneous, mostly antibiotic susceptible,
      genetic population.

PMID- 16436427
TI  - Biofilm formation in Campylobacter jejuni.
AB  - The major gastrointestinal pathogen Campylobacter jejuni is shown to exist as
      three forms of monospecies biofilm in liquid culture. It attaches to a glass
      surface; forms an unattached aggregate (floc); and forms a pellicle at the liquid
      gas interface. The three forms of biofilm resemble each other when examined by
      scanning electron microscopy. The biofilm mode of growth confers protection
      against environmental stress, the microaerobic bacteria in flocs surviving up to
      24 days at ambient temperature and atmosphere compared to 12 days survival by
      planktonic bacteria. The wild-type strains C. jejuni 33106, 32799, 33084 and
      31485 did not form flocs, and floc formation was reduced in strains mutant in a
      putative flagellar protein (FliS) and in a phosphate acetyltransferase (Cj0688).
      All other strains tested, including strains with mutations affecting capsular
      polysaccharide (kpsM), flagella (maf5), protein glycosylation (pglH) and lipo
      oligosaccharide (neuB1) formed flocs. Similarly, all strains tested formed a
      pellicle and attached to glass except the aflagellate mutant maf5; pellicle
      formation was reduced in fliS and cj0688 mutants. Different mechanisms,
      therefore, may control formation of different forms of biofilm. It is proposed
      that these poorly characterized forms of growth are important for the persistence
      of C. jejuni in the environment and may in part explain the high incidence of
      Campylobacter-associated food borne disease.

PMID- 16436428
TI  - Homocysteine accumulation causes a defect in purine biosynthesis: further
      characterization of Schizosaccharomyces pombe methionine auxotrophs.
AB  - Methionine synthase (EC2.1.1.14) catalyses the final step in methionine
      synthesis, i.e. methylation of homocysteine. A search of the Schizosaccharomyces
      pombe genomic database revealed a gene designated SPAC9.09, encoding a protein
      with significant homology to methionine synthase. Disruption of SPAC9.09 caused
      methionine auxotrophy, and thus the gene was identified as a methionine synthase
      and designated met26. The met26 mutant was found to exhibit a remarkable growth
      defect in the absence of adenine even in medium supplemented with methionine.
      This phenotype was not observed in other methionine auxotrophs. In the budding
      yeast Saccharomyces cerevisiae, which has been reported to utilize homocysteine
      in cysteine synthesis, lack of a functional methionine synthase did not cause a
      requirement for adenine. The introduction of genes from Sac. cerevisiae
      constituting the cystathionine pathway (CYS4 and CYS3) into Sch. pombe Deltamet26
      cells restored growth in the absence of adenine. HPLC analysis showed that total
      homocysteine content in Deltamet26 cells was higher than in other methionine
      auxotrophs and that introduction of the Sac. cerevisiae cystathionine pathway
      decreased total homocysteine levels. These data demonstrate that accumulation of
      homocysteine causes a defect in purine biosynthesis in the met26 mutant.

PMID- 16436429
TI  - Influence of the regulatory protein RsmA on cellular functions in Pseudomonas
      aeruginosa PAO1, as revealed by transcriptome analysis.
AB  - RsmA is a posttranscriptional regulatory protein in Pseudomonas aeruginosa that
      works in tandem with a small non-coding regulatory RNA molecule, RsmB (RsmZ), to
      regulate the expression of several virulence-related genes, including the N-acyl
      homoserine lactone synthase genes lasI and rhlI, and the hydrogen cyanide and
      rhamnolipid biosynthetic operons. Although these targets of direct RsmA
      regulation have been identified, the full impact of RsmA on cellular activities
      is not as yet understood. To address this issue the transcriptome profiles of P.
      aeruginosa PAO1 and an isogenic rsmA mutant were compared. Loss of RsmA altered
      the expression of genes involved in a variety of pathways and systems important
      for virulence, including iron acquisition, biosynthesis of the Pseudomonas
      quinolone signal (PQS), the formation of multidrug efflux pumps, and motility.
      Not all of these effects can be explained through the established regulatory
      roles of RsmA. This study thus provides both a first step towards the
      identification of further genes under RsmA posttranscriptional control in P.
      aeruginosa and a fuller understanding of the broader impact of RsmA on cellular
      functions.

PMID- 16436430
TI  - Putative glycogen-accumulating organisms belonging to the Alphaproteobacteria
      identified through rRNA-based stable isotope probing.
AB  - Deterioration of enhanced biological phosphorus removal (EBPR) has been linked to
      the proliferation of glycogen-accumulating organisms (GAOs), but few organisms
      possessing the GAO metabolic phenotype have been identified. An unidentified GAO
      was highly enriched in a laboratory-scale bioreactor and attempts to identify
      this organism using conventional 16S rRNA gene cloning had failed. Therefore,
      rRNA-based stable isotope probing followed by full-cycle rRNA analysis was used
      to specifically identify the putative GAOs based on their characteristic
      metabolic phenotype. The study obtained sequences from a group of
      Alphaproteobacteria not previously shown to possess the GAO phenotype, but 90 %
      identical by 16S rRNA gene analysis to a phylogenetic clade containing cloned
      sequences from putative GAOs and the isolate Defluvicoccus vanus. Fluorescence in
      situ hybridization (FISH) probes (DF988 and DF1020) were designed to target the
      new group and post-FISH chemical staining demonstrated anaerobic-aerobic cycling
      of polyhydroxyalkanoates, as per the GAO phenotype. The successful use of probes
      DF988 and DF1020 required the use of unlabelled helper probes which increased
      probe signal intensity up to 6.6-fold, thus highlighting the utility of helper
      probes in FISH. The new group constituted 33 % of all Bacteria in the lab-scale
      bioreactor from which they were identified and were also abundant (51 and 55 % of
      Bacteria) in two other similar bioreactors in which phosphorus removal had
      deteriorated. Unlike the previously identified Defluvicoccus-related organisms,
      the group identified in this study were also found in two full-scale treatment
      plants performing EBPR, suggesting that this group may be industrially relevant.

PMID- 16436431
TI  - The DNA-binding domain of the Escherichia coli CpxR two-component response
      regulator is constitutively active and cannot be fully attenuated by fused
      adjacent heterologous regulatory domains.
AB  - Two-component systems (TCS) based on a sensor histidine kinase and a
      phosphorylated cognate target regulator allow rapid responses to environmental
      changes. TCS are highly evolutionarily conserved, though in only a few cases are
      the inducing signals understood. This study focuses on the Escherichia coli CpxR
      response regulator that responds to periplasmic and outer-membrane stress. N
      terminal deletion mutations have been isolated that render the transcription
      factor constitutively active, indicating that the N terminus functions, in part,
      to keep the C-terminal winged-helix DNA-binding effector domain in an inactive
      state. Analysis of truncations spanning the CpxR interdomain region revealed that
      mutants retaining the alpha5 helix significantly augment activation. Hybrid
      proteins obtained by fusing the CpxR effector domain to structurally similar
      heterologous N-terminal regulatory domains, or even GFP, failed to restore
      repression to the C-terminal domain. These findings shed light on the mechanism
      of CpxR effector domain activation and on the investigation of constitutive
      mutants obtained by truncation in other TCS.

PMID- 16436432
TI  - The Sinorhizobium meliloti chromosomal origin of replication.
AB  - The predicted chromosomal origin of replication (oriC) from the alfalfa symbiont
      Sinorhizobium meliloti is shown to allow autonomous replication of a normally non
      replicating plasmid within S. meliloti cells. This is the first chromosomal
      replication origin to be experimentally localized in the Rhizobiaceae and its
      location, adjacent to hemE, is the same as for oriC in Caulobacter crescentus,
      the only experimentally characterized alphaproteobacterial oriC. Using an
      electrophoretic mobility shift assay and purified S. meliloti DnaA replication
      initiation protein, binding sites for DnaA were mapped in the S. meliloti oriC
      region. Mutations in these sites eliminated autonomous replication. S. meliloti
      that expressed DnaA from a plasmid lac promoter was observed to form pleomorphic
      filamentous cells, suggesting that cell division was perturbed. Interestingly,
      this cell phenotype is reminiscent of differentiated bacteroids found inside
      plant cells in alfalfa root nodules.

PMID- 16436433
TI  - Production and properties of the native Chromobacterium violaceum fucose-binding
      lectin (CV-IIL) compared to homologous lectins of Pseudomonas aeruginosa (PA-IIL)
      and Ralstonia solanacearum (RS-IIL).
AB  - Chromobacterium violaceum is a versatile, violet pigment (violacein)-producing
      beta-proteobacterium, confined to tropical and subtropical regions, dwelling in
      soil and water, like Pseudomonas aeruginosa and Ralstonia solanacearum. These
      three bacteria are saprophytes that occasionally become aggressive opportunistic
      pathogens virulently attacking animals (the first two) and plants (the third).
      The recent availability of their genome sequences enabled identification in the
      C. violaceum genome of an ORF (locus no. 1744) that is similar to those of P.
      aeruginosa and R. solanacearum lectins, PA-IIL and RS-IIL, respectively. A
      recombinant protein, CV-IIL, encoded by that ORF exhibited fucose>mannose
      specific lectin activity resembling PA-IIL. This paper describes production and
      properties of the native CV-IIL, which, like PA-IIL and RS-IIL, is probably also
      a quorum-sensing-driven secondary metabolite, appearing concomitantly with
      violacein. Its formation is repressed in the CV026 mutant of C. violaceum, which
      lacks endogenous N-acylhomoserine lactone. The upstream extragenic sequence of
      its ORF contains a 20 bp sequence (5'-101-120) with partial similarities to the
      luxI-box and the related P. aeruginosa and R. solanacearum promoter boxes of
      quorum-sensing-controlled genes. The lectin level is augmented by addition of
      trehalose to the medium. The subunit size of CV-IIL (around 11.86 kDa) is similar
      to those of PA-IIL (11.73 kDa) and RS-IIL (11.60 kDa). Like PA-IIL, in the
      tetrameric form CV-IIL preferentially agglutinates alpha1-2 fucosylated H
      positive human erythrocytes (regardless of their A, B or O type), as opposed to
      the O(h) Bombay type, but differs from it in having no interaction with rabbit
      erythrocytes and in displaying stronger affinity to l-galactose than to l-fucose.
      The greater similarity of CV-IIL to PA-IIL than to RS-IIL might be related to the
      selective adaptation of both C. violaceum and P. aeruginosa to animal tissues
      versus the preferential homing of R. solanacearum to plants.

PMID- 16436434
TI  - SoxV transfers electrons to the periplasm of Paracoccus pantotrophus - an
      essential reaction for chemotrophic sulfur oxidation.
AB  - The soxVW genes are located upstream of the sox gene cluster encoding the sulfur
      oxidizing ability of Paracoccus pantotrophus. SoxV is highly homologous to CcdA,
      which is involved in cytochrome c maturation of P. pantotrophus. SoxV was shown
      to function in reduction of the periplasmic SoxW, which shows a CysXaaXaaCys
      motif characteristic for thioredoxins. From strain GBOmegaV, which carries an
      Omega-kanamycin-resistance-encoding interposon in soxV, and complementation
      analysis it was evident that SoxV but not the periplasmic SoxW was essential for
      lithoautotrophic growth of P. pantotrophus with thiosulfate. However, the
      thiosulfate-oxidizing activities of cell extracts from the wild-type and from
      strain GBOmegaV were similar, demonstrating that the low thiosulfate-oxidizing
      activity of strain GBOmegaV in vivo was not due to a defect in biosynthesis or
      maturation of proteins of the Sox system and suggesting that SoxV is part of a
      regulatory or catalytic system of the Sox system. Analysis of DNA sequences
      available from different organisms harbouring a Sox system revealed that soxVW
      genes are exclusively present in sox operons harbouring the soxCD genes, encoding
      sulfur dehydrogenase, suggesting that SoxCD might be a redox partner of SoxV. No
      complementation of the ccdA mutant P. pantotrophus TP43 defective in cytochrome c
      maturation was achieved by expression of soxV in trans, demonstrating that the
      high identity of SoxV and CcdA does not correspond to functional homology.

PMID- 16436435
TI  - Functional analysis of the competence transcription factor ComK of Bacillus
      subtilis by characterization of truncation variants.
AB  - The competence transcription factor ComK is the master regulator of competence
      development in Bacillus subtilis. In the regulatory pathway, ComK is involved in
      different interactions: (i) protein-DNA interactions to stimulate transcription
      of ComK-dependent genes and (ii) protein-protein interactions, divided into
      interactions with other proteins and interactions between ComK proteins involving
      oligomerization. The fact that ComK displays different types of interactions
      suggests the presence of specific, distinct domains in the protein. This paper
      describes a search for functional domains, by constructing ComK truncation
      variants, which were tested for DNA binding, oligomerization and transcription
      activation. Truncations at the C-terminal end of ComK demonstrated the
      requirement of this part for transcription activation, but not for DNA binding.
      The C-terminal region is probably involved in oligomerization of ComK-dimers into
      tetramers. Surprisingly, a ComK truncation variant lacking 9 aa from the N
      terminal end (DeltaN9ComK) showed higher transcription activation than wild-type
      ComK, when expressed in Lactococcus lactis. However, in B. subtilis,
      transcription activation by DeltaN9ComK was twofold lower than that by wild-type
      ComK, resulting from a five- to sixfold lower protein level of ComKDeltaN9. Thus,
      relatively, DeltaN9ComK is more active in transcription activation than wild-type
      ComK. These results suggest that the presence of this N-terminal extension on
      ComK is a trade-off between high transcription activation and a thus far
      unidentified role in regulation of ComK.

PMID- 16436436
TI  - Regulation of Serratia marcescens ompF and ompC porin genes in response to
      osmotic stress, salicylate, temperature and pH.
AB  - Serratia marcescens is a Gram-negative enterobacterium that has become an
      important opportunistic pathogen, largely due to its high degree of natural
      antibiotic resistance. One factor contributing to this natural antibiotic
      resistance is reduced outer membrane permeability, which is controlled in part by
      OmpC and OmpF porin proteins. OmpF expression is regulated by micF, an RNA
      transcript encoded upstream of the ompC gene, which hybridizes with the ompF
      transcript to inhibit its translation. Regulation of S. marcescens porin gene
      expression, as well as that of micF, was investigated using beta-galactosidase
      reporter gene fusions in response to 5, 8 and 10 % sucrose, 1, 5 and 8 mM
      salicylate, and different pH and temperature values. beta-Galactosidase activity
      assays revealed that a lower growth temperature (28 degrees C), a more basic pH
      (pH 8), and an absence of sucrose and salicylate induce the transcription of the
      ompF gene, whereas the induction of ompC is stimulated at a higher growth
      temperature (42 degrees C), acidic pH (pH 6), and maximum concentrations of
      sucrose (10 %) and salicylate (8 mM). In addition, when multiple conditions were
      tested, temperature had the predominant effect, followed by pH. In this study, it
      was found that the MicF regulatory mechanism does not play a role in the
      osmoregulation of the ompF and ompC genes, whereas MicF does repress OmpF
      expression in the presence of salicylate and high growth temperature, and under
      low pH conditions.

PMID- 16436437
TI  - The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates
      PBPA, a penicillin-binding protein required for cell division.
AB  - A cluster of genes encoded by ORFs Rv0014c-Rv0018c in Mycobacterium tuberculosis
      encodes candidate cell division proteins RodA and PBPA, a pair of
      serine/threonine kinases (STPKs), PknA and PknB, and a phosphatase, PstP. The
      organization of genes encompassing this region is conserved in a large number of
      mycobacterial species. This study demonstrates that recombinant PBPA of M.
      tuberculosis binds benzylpenicillin. Knockout of its counterpart in M. smegmatis
      resulted in hindered growth and defective cell septation. The phenotype of the
      knockout (PBPA-KO) could be restored to that of the wild-type upon expression of
      PBPA of M. tuberculosis. PBPA localized to the division site along with newly
      synthesized peptidoglycan, between segregated nucleoids. In vivo coexpression of
      PBPA and PknB, in vitro kinase assays and site-specific mutagenesis substantiated
      the view that PknB phosphorylates PBPA on T362 and T437. A T437A mutant could not
      complement PBPA-KO. These studies demonstrate for the first time that PBPA, which
      belongs to a subclass of class B high-molecular-mass PBPs, plays an important
      role in cell division and cell shape maintenance. Signal transduction mediated by
      PknB and PstP likely regulates the positioning of this PBP at the septum, thereby
      regulating septal peptidoglycan biosynthesis.

PMID- 16436438
TI  - Metagenomic analysis of mesopelagic Antarctic plankton reveals a novel
      deltaproteobacterial group.
AB  - Phylogenetic screening of 3200 clones from a metagenomic library of Antarctic
      mesopelagic picoplankton allowed the identification of two bacterial 16S-rDNA
      containing clones belonging to the Deltaproteobacteria, DeepAnt-1F12 and DeepAnt
      32C6. These clones were very divergent, forming a monophyletic cluster with the
      environmental sequence GR-WP33-58 that branched at the base of the myxobacteria.
      Except for the possession of complete rrn operons without associated tRNA genes,
      DeepAnt-1F12 and DeepAnt-32C6 were very different in gene content and
      organization. Gene density was much higher in DeepAnt-32C6, whereas nearly one
      third of DeepAnt-1F12 corresponded to intergenic regions. Many of the predicted
      genes encoded by these metagenomic clones were informational (i.e. involved in
      replication, transcription, translation and related processes). Despite this, a
      few putative cases of horizontal gene transfer were detected, including a
      transposase. DeepAnt-1F12 contained one putative gene encoding a long cysteine
      rich protein, probably membrane-bound and Ca2+-binding, with only eukaryotic
      homologues. DeepAnt-32C6 carried some predicted genes involved in metabolic
      pathways that suggested this organism may be anaerobic and able to ferment and to
      degrade complex compounds extracellularly.

PMID- 16436439
TI  - Comparative analysis of antibiotic resistance gene markers in Mycoplasma
      genitalium: application to studies of the minimal gene complement.
AB  - Mycoplasma genitalium has been proposed as a suitable model for an in-depth
      understanding of the biology of a free-living organism. This paper reports that
      the expression of the aminoglycoside resistance gene aac(6')-aph(2''), the only
      selectable marker hitherto available for M. genitalium genetic studies,
      correlates with a growth impairment of the resistant strains. In light of this
      finding, a tetM438 construction based on the tetracycline resistance gene tetM
      was developed; it can be used efficiently in M. genitalium and confers multiple
      advantages when compared to aac(6')-aph(2''). The use of tetM438 significantly
      improves transformation efficiency and generates visible colonies faster.
      Finally, the improvements in the pMTnTetM438 construction made it possible to
      obtain insertions in genes which have not been previously considered to be
      dispensable under laboratory growth conditions.

PMID- 16436440
TI  - The structural proteome of Pseudomonas aeruginosa bacteriophage phiKMV.
AB  - The structural proteome of phiKMV, a lytic bacteriophage infecting Pseudomonas
      aeruginosa, was analysed using two approaches. In one approach, structural
      proteins of the phage were fractionated by SDS-PAGE for identification by liquid
      chromatography-mass spectrometry (LC-MS). In a second approach, a whole-phage
      shotgun analysis (WSA) was applied. WSA uses trypsin digestion of whole phage
      particles, followed by reversed-phase HPLC and gas-phase fractionation of the
      complex peptide mixture prior to MS. The results yield a comprehensive view of
      structure-related proteins in phiKMV and suggest subtle structural differences
      from phage T7.

PMID- 16436441
TI  - Phenol/water extract of Treponema socranskii subsp. socranskii as an antagonist
      of Toll-like receptor 4 signalling.
AB  - Treponema socranskii is one of the most frequently found oral spirochaetes in
      periodontitis and endodontic infections. LPS or glycolipids from bacteria are
      potent stimulators of innate immune and inflammatory systems. In this study the
      bioactivity of a phenol/water extract from T. socranskii subsp. socranskii (TSS
      P) was analysed. TSS-P showed minimal endotoxicity and no inducing potential for
      proinflammatory cytokines (TNF-alpha and IL-8) or for intercellular adhesion
      molecule-1 (ICAM-1) in human monocyte cell line THP-1 cells and primary cultured
      human gingival fibroblasts. Rather, it inhibited ICAM-1 expression and IL-8
      secretion from cells stimulated by the LPS of Escherichia coli and Actinobacillus
      actinomycetemcomitans, which are known to be Toll-like receptor 4 (TLR4)
      agonists. However, this antagonistic activity was not shown in cells stimulated
      by peptidoglycan or IL-1beta. As its antagonistic mechanism, TSS-P blocked the
      binding of E. coli LPS to LPS-binding protein (LBP) and CD14, which are molecules
      involved in the recruitment of LPS to the cell membrane receptor complex TLR4-MD
      2 for the intracellular signalling of LPS. TSS-P itself did not bind to MD-2 or
      THP-1 cells, but inhibited the binding of E. coli LPS to MD-2 or to the cells in
      the presence of serum (which could be replaced by recombinant human LBP and
      recombinant human CD14). The results suggest that TSS-P acts as an antagonist of
      TLR4 signalling by interfering with the functioning of LBP/CD14.

PMID- 16436442
TI  - MfLIP1, a gene encoding an extracellular lipase of the lipid-dependent fungus
      Malassezia furfur.
AB  - Malassezia furfur is a dimorphic fungus and a member of the normal cutaneous
      microflora of humans. However, it is also a facultative pathogen, associated with
      a wide range of skin diseases. One unusual feature of M. furfur is an absolute
      dependency on externally provided lipids which the fungus hydrolyses by lipolytic
      activity to release fatty acids necessary for both growth and pathogenicity. In
      this study, the cloning and characterization of the first gene encoding a
      secreted lipase of M. furfur possibly associated with this activity are reported.
      The gene, MfLIP1, shows high sequence similarity to other known extracellular
      lipases, but is not a member of a lipase gene family in M. furfur. MfLIP1
      consists of 1464 bp, encoding a protein with a molecular mass of 54.3 kDa, a
      conserved lipase motif and an N-terminal signal peptide of 26 aa. By using a
      genomic library, two other genes were identified flanking MfLIP1, one of them
      encoding a putative secreted catalase, the other a putative amine oxidase. The
      cDNA of MfLIP1 was expressed in Pichia pastoris and the biochemical properties of
      the recombinant lipase were analysed. MfLip1 is most active at 40 degrees C and
      the pH optimum was found to be 5.8. The lipase hydrolysed lipids, such as Tweens,
      frequently used as the source of fatty acids in M. furfur media, and had minor
      esterase activity. Furthermore, the lipase is inhibited by different bivalent
      metal ions. This is the first molecular description of a secreted lipase from M.
      furfur.

PMID- 16436443
TI  - The uptake of a Klebsiella pneumoniae capsule polysaccharide mutant triggers an
      inflammatory response by human airway epithelial cells.
AB  - The means by which airway epithelial cells sense a bacterial infection and which
      intracellular signalling pathways are activated upon infection are poorly
      understood. A549 cells and human primary airway cells (NHBE) were used to
      investigate the response to infection with Klebsiella pneumoniae. Infection of
      A549 and NHBE with K. pneumoniae 52K10, a capsule polysaccharide (CPS) mutant,
      increased the surface levels of ICAM-1 and caused the release of IL-8. By
      contrast, the wild-type strain did not elicit these responses. Consistent with a
      functional role for these responses, there was a correlation between ICAM-1
      levels and the number of adherent leukocytes on the epithelial cell surface. In
      addition, treatment of neutrophils with IL-8 enhanced their ability to kill K.
      pneumoniae. Strain 52K10 was internalized by A549 cells more efficiently than the
      wild-type, and when infections with 52K10 were performed in the presence of
      cytochalasin D the inflammatory response was abrogated. These findings suggest
      that cellular activation is mediated by bacterial internalization and that CPS
      prevents the activation through the blockage of bacterial adhesion and uptake.
      Collectively, the results indicate that bacterial internalization by airway
      epithelial cells could be the triggering signal for the activation of the innate
      immune system of the airway. Infection of A549 cells by 52K10 was shown to
      trigger the nuclear translocation of NF-kappaB. Evidence is presented showing
      that 52K10 activated IL-8 production through Toll-like receptor (TLR) 2 and TLR4
      pathways and that A549 cells could use soluble CD14 as TLR co-receptor.

PMID- 16436444
TI  - Transcriptional and translational expression patterns associated with immobilized
      growth of Campylobacter jejuni.
AB  - Although Campylobacter jejuni is a leading cause of food-borne illness, little is
      known about the mechanisms by which this pathogen mediates prolonged
      environmental survival or host cell virulence. Although these behaviours
      represent distinct phenotypes, they share a common requirement of an immobilized
      state. In order to understand the cellular mechanisms that facilitate a surface
      associated lifestyle, transcriptional and translational expression profiles were
      determined for sessile and planktonic C. jejuni. These investigations indicate
      that the immobilized bacteria undergo a shift in cellular priorities away from
      metabolic, motility and protein synthesis capabilities towards emphasis on iron
      uptake, oxidative stress defence and membrane transport. This pattern of
      expression partially overlaps those reported for Campylobacter during host
      colonization, as well as for other species of bacteria involved in biofilms,
      highlighting common adaptive responses to the conserved challenges within each of
      these phenotypes. The adaptation of Campylobacter to immobilized growth may
      represent a quasi-differentiated state that functions as a foundation for further
      specialization towards phenotypes such as biofilm formation or host cell
      virulence.

PMID- 16436445
TI  - Second-hand smoke levels in UK pubs and bars: do the English Public Health White
      Paper proposals go far enough?
AB  - BACKGROUND: The English Public Health White Paper proposes introducing smoke-free
      workplaces except in pubs and bars that do not prepare and serve food. The bar
      area will be non-smoking in exempted pubs. OBJECTIVE: To explore the likely
      impact of these proposals in UK pubs and bars. METHODS: A total of 59 pubs and
      bars within Greater Manchester in 2001 were chosen. Thirteen were mechanically
      ventilated, 12 were naturally ventilated and 34 had extractor fans; 23 provided
      non-smoking areas. We measured time-weighted average concentrations of respirable
      suspended particles (RSP), solanesol tobacco-specific particles and vapour-phase
      nicotine (VPN) over a 4-h sampling period on a Tuesday or Saturday night.
      RESULTS: Second-hand smoke (SHS) levels in smoking areas were high (mean RSP
      114.5 microg/m3, VPN 88.2 microg/m3, solanesol 101.7 microg/m3). There were only
      small (5-13 per cent) reductions in bar areas. Mean levels were lower in non
      smoking areas: by 33 per cent for RSPs, 52 per cent for solanesol particles and
      69 per cent for VPN. Compared with other settings (homes and other workplaces)
      with unrestricted smoking, mean SHS levels were high throughout all areas of the
      pubs regardless of ventilation strategy. CONCLUSION: Partial measures, like those
      in the English Public Health White Paper, will leave bar staff in exempted pubs
      unprotected from the occupational hazard of SHS.

PMID- 16436446
TI  - Improving health through neighbourhood environmental change: are we speaking the
      same language? A qualitative study of views of different stakeholders.
AB  - OBJECTIVE: To explore the perspectives of four groups of stakeholders to proposed
      improvements to the built environment-a neighbourhood renewal consisting of a
      home zone development and an extension of the National Cycle Network (NCN).
      Design Qualitative focus group study. Setting A deprived neighbourhood. Sample
      Four focus groups were conducted with 10 residents from the neighbourhood
      undergoing change, nine pupils from a local primary school, 10 students and
      tutors from a local further education college and three local authority planners
      overseeing the developments. RESULTS: We identified four main themes relating to
      the impact of environmental change. These were safety, space, antisocial
      behaviour and physical activity and health, the latter being the least important
      to all groups. A mismatch regarding environmental change emerged in perspectives
      between different stakeholders. The residents were most concerned about home and
      car (parking) safety and in particular felt that the new cycle/walk way would
      reduce their safety, whereas the planners felt that the environmental change
      would provide a safer and healthier environment for the residents. CONCLUSION:
      The assumption that planned provision of supportive environments will improve
      levels of physical activity, health and lifestyle may not be true if the
      developments do not take account of community concerns regarding personal safety.

PMID- 16436447
TI  - Flu vaccination in nursing homes: a survey of nursing-home managers.
AB  - BACKGROUND: This article describes the findings of a survey of nursing-home
      managers in the Sefton area of Merseyside about flu vaccination in their nursing
      homes during the 2002/2003 flu vaccination campaign. This followed concerns
      expressed that significant numbers of nursing-home residents may not have been
      offered the vaccine during the annual campaign. METHODS: A survey of all nursing
      homes in Sefton carried out in April 2003. RESULTS: Forty-three nursing homes
      participated in the study. Survey results showed considerable variation in
      practice with regard to the organization of flu vaccination and consequently
      considerable variation in the outcomes achieved with regard to the number of
      residents vaccinated. Residents are more likely to be offered vaccination in some
      homes than others. The size of the home and the number of qualified staff may be
      influential. Some homes report uncertainty related to the issues of consent and
      anaphylaxis and problems obtaining vaccine prescriptions. However, attitudes of
      nursing-home managers may also be important.

PMID- 16436448
TI  - Prevalence of problematic and injecting drug use for Drug Action Team areas in
      England.
AB  - BACKGROUND: National and local monitoring of policies on illicit drug use
      requires information on the number of problematic drug users in a country. This
      article reports the findings from a study that estimated the number of
      problematic and injecting drug users for all Drug Action Teams (DATs) in England
      for 2001. METHODS: The Multiple Indicator Method (MIM) is a statistical technique
      for using aggregated data to estimate numbers of drug users across a large number
      of areas. The MIM was used to combine eight indicators available for all DATs,
      with prevalence estimates available from a small number of DATs. The indicators
      were drug possession and supply offences, arrest referrals, people recorded in
      drug treatment databases, methadone prescriptions, drug-related hospital
      episodes, drug-related deaths and DATs' Townsend score. The latter is a measure
      of material deprivation. A three-stage process involved, (i) factor analysis of
      the drug indicators, (ii) regression linking factor scores to known prevalence
      estimates and (iii) imputation of estimates to all other DATs. RESULTS: Factor
      analysis yielded two statistically significant factors underlying the drug
      indicators in 150 DATs in England. The estimated prevalence rate of problematic
      drug use in the DATs varied from 0.2 to 1.5 per cent of the population. The
      estimated average number of problematic drug users per DAT was 1943 (standard
      deviation = 1300). The estimated average number of injecting drug users per DAT
      was 627 (standard deviation = 572). The estimates for England in 2001 were
      287,670 (population rate = 0.64 per cent) problem drug users, and 93,185
      (population rate = 0.23 per cent) injecting drug users. CONCLUSIONS: Although the
      model cannot take account of specific local factors, the results are likely to be
      accurate in areas that do not have these idiosyncrasies. The estimated prevalence
      figures provide a basis for all DATs to assess their contact rates with
      problematic and injecting drug users.

PMID- 16436449
TI  - Is a target culture in health care always compatible with efficient use of
      resources? A cost-effectiveness analysis of an intervention to achieve
      thrombolysis targets.
AB  - BACKGROUND: The UK government has attempted to improve the quality of health care
      in the National Health Service and minimize geographical variations in quality by
      imposing targets in certain areas of health care. The measures taken by local
      health economies to achieve these targets have not before been subjected to cost
      effectiveness analysis. We have assessed the cost effectiveness of an
      intervention designed to achieve thrombolysis time targets. METHODS: In the
      setting of a single district general hospital in England, we audited local pain
      to-needle (PTN) and door-to-needle (DTN) times, before and after a pounds 208,000
      (Euro 310,000, dollar 370,000) annual expenditure to improve performance against
      government targets. The intervention included the recruitment of additional
      nursing time in the Accident & Emergency Department and the use of a single bolus
      thrombolytic agent for all patients with ST elevation myocardial infarction. An
      economic evaluation was performed, based on the expected number of additional
      lives saved, extrapolated from a meta-analysis of previous thrombolysis trials.
      RESULTS: The intervention reduced mean DTN time from 37.6 +/- 5.9 minutes (mean
      +/- SEM) to 27.6 +/- 3.6 minutes (p = 0.06). The cost per life saved was pounds
      3,423 +/- 850 (Euro 5,100,000, dollar 6,100,000), the cost per life year gained
      was pounds 222,184 (Euro 330,000, dollar 390,000) and the cost per quality
      adjusted life year (QALY) gained was pounds 246,871 (Euro 370,000, dollar
      440,000). CONCLUSION: Although moderately successful at improving performance
      against government targets, this intervention to promote rapid thrombolysis
      proved to be an inefficient use of health-care resources. Strict government
      targets in health care may not always lead to efficient targeting of resources.

PMID- 16436450
TI  - Estimating diabetes prevalence by small area in England.
AB  - BACKGROUND: Diabetes risk is linked to both deprivation and ethnicity, and so
      prevalence will vary considerably between areas. Prevalence differences may
      partly account for geographic variation in health performance indicators for
      diabetes, which are based on age standardized hospitalization or operation rates.
      A positive correlation between prevalence and health outcomes indicates that the
      latter are not measuring only performance. METHODS: A regression analysis of
      prevalence rates according to age, sex and ethnicity from the Health Survey for
      England (HSE) is undertaken and used (together with census data) to estimate
      diabetes prevalence for 354 English local authorities and 8000 smaller areas
      (electoral wards). An adjustment for social factors is based on a prevalence
      gradient over area-deprivation quintiles. A Bayesian estimation approach is used
      allowing simple inclusion of evidence on prevalence from other or historical
      sources. RESULTS: The estimated prevalent population in England is 1.5 million
      (188 000 type 1 and 1.341 million type 2). At strategic health authority (StHA)
      level, prevalence varies from 2.4 (Thames Valley) to 4 per cent (North East
      London). The prevalence estimates are used to assess variations between local
      authorities in adverse hospitalization indicators for diabetics and to assess the
      relationship between diabetes-related mortality and prevalence. In particular,
      rates of diabetic ketoacidosis (DKA) and coma are positively correlated with
      prevalence, while diabetic amputation rates are not. CONCLUSIONS: The methodology
      developed is applicable to developing small-area-prevalence estimates for a range
      of chronic diseases, when health surveys assess prevalence by demographic
      categories. In the application to diabetes prevalence, there is evidence that
      performance indicators as currently calculated are not corrected for prevalence.

PMID- 16436451
TI  - Our farmers at risk: behaviour and belief system in pesticide safety.
AB  - BACKGROUND: The study was done in three villages in Nueva Ecija, Philippines. It
      surveys farmers' belief system and pesticide practices relative to health and
      safety. METHODS: Initially it used a simulated market study on willingness to pay
      for personal protective equipment in the form of gloves and masks. Then a
      combination of semi-structured, formal, informal, and key-informant interviews,
      as well as focus groups, and field observations was done intermittently in a span
      of approximately 12 years. RESULTS: The farmers perceive illness in terms of
      inability to function. Pesticide to them may not be a threat because (i) they are
      immune, (ii) it is regarded as a medicine that is needed by the plants rather
      than poison, and (iii) exposure is only through inhalation and ingestion not
      through dermal contact. Added to that, they put value on pasma, and try to
      prevent it at the cost of exposure to pesticides. These perceptions lead to their
      practices showing inadequate protection. CONCLUSION: There is the need for more
      health education programs that tap farmers' belief system and cognitive
      categories to stress the need for precautions.

PMID- 16436452
TI  - Socioeconomic deprivation, coronary heart disease prevalence and quality of care:
      a practice-level analysis in Rotherham using data from the new UK general
      practitioner Quality and Outcomes Framework.
AB  - BACKGROUND: The provision of coronary heart disease (CHD) health care has been
      shown to be inequitous, with those most in need having the least access to high
      quality care. The new UK general practitioner (GP) Quality and Outcomes Framework
      (QOF) contract offers substantial financial rewards to general practices that
      combine maximal CHD case finding with high-quality CHD care. OBJECTIVE: To
      examine whether GP practice-level CHD prevalence and the measures of quality of
      care derived from the new QOF data are associated with area-level socioeconomic
      deprivation. METHODS: An ecological study of 38 GP practices contracting with
      Rotherham Primary Care Trust, United Kingdom, was carried out. We calculated
      Spearman rank correlation coefficients for practice-level age-sex-standardized
      QOF CHD prevalence against area deprivation score and for 11 QOF CHD indicator
      achievements against area deprivation score. RESULTS: Practice-level CHD
      prevalence showed a positive correlation with deprivation (r=0.64, p<0.001), as
      did one of the 11 quality-of-care indicators (recording of smoking status,
      r=0.34, p=0.04). The remaining 10 quality-of-care indicators showed no
      significant correlation with deprivation. CONCLUSION: Practice-level CHD
      prevalence is associated with deprivation, but we found no evidence of
      socioeconomic inequality in CHD care. This finding is in contrast to that from
      previous studies and the widely reported inverse care law.

PMID- 16436453
TI  - Redesigning Bacillus thuringiensis Cry1Aa toxin into a mosquito toxin.
AB  - The Bacillus thuringiensis crystal protein Cry1Aa is normally selectively active
      to caterpillar larvae. Through rational design, toxicity (microg/ml) to the
      mosquito Culex pipiens was introduced by selected deletions and substitutions of
      the loop residues of domain II. Toxicity to its natural target Manduca sexta was
      concomitantly abolished. The successful grafting of the alternate mosquito
      toxicity onto the original lepidopteran Cry1Aa toxin demonstrates the possibility
      of designing and engineering a desired toxicity into any toxin of a common
      scaffold by reshaping the receptor binding region with desired specificities.

PMID- 16436455
TI  - Extended tracts of homozygosity in outbred human populations.
AB  - Long tracts of consecutive homozygous single nucleotide polymorphisms (SNPs) can
      arise in the genome through a number of mechanisms. These include inbreeding in
      which an individual inherits chromosomal segments that are identical by descent
      from each parent. However, recombination and other processes break up chromosomal
      segments over generations. The longest tracts are therefore to be expected in
      populations with an appreciable degree of inbreeding. We examined the length,
      number and distribution of long tracts of homozygosity in the apparently outbred
      HapMap populations. We observed 1393 tracts exceeding 1 Mb in length among the
      209 unrelated HapMap individuals. The longest was an uninterrupted run of 3922
      homozygous SNPs spanning 17.9 Mb in a Japanese individual. We find that
      homozygous tracts are significantly more common in regions with high linkage
      disequilibrium and low recombination, and the location of tracts is similar
      across all populations. The Yoruba sample has the fewest long tracts per
      individual, consistent with a larger number of generations (and hence amount of
      recombination) since the founding of that population. Our results suggest that
      multiple-megabase-scale ancestral haplotypes persist in outbred human populations
      in broad genomic regions which have lower than average recombination rates. We
      observed three outlying individuals who have exceptionally long and numerous
      homozygous tracts that are not associated with recombination suppressed areas of
      the genome. We consider that this reflects a high level of relatedness in their
      ancestry which is too recent to have been influenced by the local recombination
      intensity. Possible alternative mechanisms and the implications of long
      homozygous tracts in the genome are discussed.

PMID- 16436454
TI  - Construction and optimization of a CC49-based scFv-beta-lactamase fusion protein
      for ADEPT.
AB  - CC49 is a clinically validated antibody with specificity for TAG-72, a
      carbohydrate epitope that is over-expressed and exposed on a large fraction of
      solid malignancies. We constructed a single chain fragment (scFv) based on CC49
      and fused it to beta-lactamase. The first generation fusion protein, TAB2.4, was
      expressed at low levels in Escherichia coli and significant degradation was
      observed during production. We optimized the scFv domain of TAB2.4 by
      Combinatorial Consensus Mutagenesis (CCM). An improved variant TAB2.5 was
      identified that resulted in an almost 4-fold improved expression and 2.5 degrees
      higher thermostability relative to its parent molecule. Soluble TAB2.5 can be
      manufactured in low-density E.coli cultures at 120 mg/l. Our studies suggest that
      CCM is a rapid and efficient method to generate antibody fragments with improved
      stability and expression. The fusion protein TAB2.5 can be used for antibody
      directed enzyme prodrug therapy (ADEPT).

PMID- 16436457
TI  - Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3.
AB  - We report the identification of mutations in a non-syndromic autosomal recessive
      congenital ichthyosis (ARCI) in a new gene mapping within a previously identified
      locus on chromosome 19p12-q12, which has been defined as LI3 in the OMIM database
      (MIM 604777). The phenotype usually presents as lamellar ichthyosis and
      hyperlinearity of palms and soles. Seven homozygous mutations including five
      missense mutations and two deletions were identified in a new gene, FLJ39501, on
      chromosome 19p12 in 21 patients from 12 consanguineous families from Algeria,
      France, Italy and Lebanon. FLJ39501 encodes a protein which was found to be a
      cytochrome P450, family 4, subfamily F, polypeptide 2 homolog of the leukotriene
      B4-omega-hydroxylase (CYP4F2) and could catalyze the 20-hydroxylation of
      trioxilin A3 from the 12(R)-lipoxygenase pathway. Further oxidation of this
      substrate by the fatty alcohol:nicotinamide-adenine dinucleotide oxidoreductase
      (FAO) enzyme complex, in which one component, ALDH3A2, is known to be mutated in
      Sjogren-Larsson syndrome (characterized by ichthyosis and spastic paraplegia),
      would lead to 20-carboxy-(R)-trioxilin A3. This compound could be involved in
      skin hydration and would be the essential missing product in most forms of ARCI.
      Its chiral homolog, 20-carboxy-(S)-trioxilin A3, could be implicated in spastic
      paraplegia and in the maintenance of neuronal integrity.

PMID- 16436456
TI  - Differential expression of novel naturally occurring splice variants of PTEN and
      their functional consequences in Cowden syndrome and sporadic breast cancer.
AB  - PTEN, a dual-phosphatase tumor suppressor, is inactivated in Cowden syndrome
      (CS), characterized by high risk of breast and thyroid cancer, and in variety of
      sporadic cancers. Despite the importance of alternative splicing, very limited
      information on its role in PTEN and associated cancers is available. We
      identified eight novel PTEN splice variants (SVs) that retained intron 3 regions
      (3a, 3b, 3c); intron 5 regions (5a, 5b, 5c); excluded part of exon 5 (DelE5) or
      all of exon 6 (DelE6), respectively. Analysis of SVs in 12 sporadic breast
      cancers revealed full-length (FL)-PTEN transcript reduction in 10; SVs 3b, 3c and
      5c not expressed in 7, 6 and 4, respectively, and under-expressed in the rest. In
      contrast, SV-5b was over-expressed in breast cancers. PTEN SV analysis in 16
      CS/CS-like patients and eight controls revealed that SV-5a is under-expressed and
      SV-3a over-expressed in the germline of CS/CS-like individuals when compared with
      controls. Although SV-5a expression decreased P-Akt level and cyclin D1 promoter
      activity, SVs 5b and 5c increased cyclin D1 promoter activity. Thus, SV-5a
      behaving like FL-PTEN corroborates our observation that SV-5a is under-expressed
      in CS when compared with controls. Similarly, SV-5b functionally counters PTEN's
      action and is over-expressed in sporadic breast cancers. Furthermore, we
      demonstrate that expression of these SVs is under the regulation of p53. Our
      observations suggest that differential expression of PTEN and its SVs could play
      a role in the pathogenesis of sporadic breast cancers and CS, and may lend a
      novel way of making a rapid molecular diagnosis of CS without mutation analysis.

PMID- 16436458
TI  - Cardiac sarcoidosis detected with magnetic resonance imaging.

PMID- 16436459
TI  - Reducing occupational psychological distress: a randomized controlled trial of a
      mailed intervention.
AB  - There are increasing levels of psychological distress among general practitioners
      (GPs). The purpose of this study is to evaluate the effectiveness of a mailed
      intervention to reduce distress among 'at-risk' GPs. A questionnaire was sent to
      1356 GPs from eight Divisions of General Practice. Out of 819 (60%) who
      responded, 233 GPs were recruited with scores indicative of psychological
      distress. These GPs were randomized to intervention (n = 120) or control (n =
      113). The intervention consisted of a simple letter feeding back and interpreting
      the psychological score together with a self-help sheet. During the study, an
      educational program was offered to GPs by Divisions of General Practice. The main
      outcome measure used was changes in psychological distress (General Health
      Questionnaire 12) score after 3 months. Significance was set at P < 0.05. Initial
      analysis of the data showed borderline significance (P = 0.05). However, analysis
      of the data post hoc excluding GPs who participated in the educational program
      showed a significant reduction in psychological distress (P = 0.03). It appears
      that there may have been a dilution of the intervention effect. Mailed
      interventions are a cost-effective way of reaching at-risk GPs and may contribute
      to a reduction in psychological morbidity.

PMID- 16436460
TI  - Chronic exposure to methylated arsenicals stimulates arsenic excretion pathways
      and induces arsenic tolerance in rat liver cells.
AB  - Although inorganic arsenicals are toxic and carcinogenic in humans, inorganic
      arsenite has recently emerged as a highly effective chemotherapeutic agent for
      acute promyelocytic leukemia (APL). Inorganic arsenicals are enzymatically
      methylated to monomethylarsonic acid (MMAs(V)), dimethylarsinic acid (DMAs(V)),
      and trimethylarsine oxide (TMAs(V)O) in mammals. We examined the effects of
      chronic exposure to methylated arsenicals on arsenic tolerance by using rat
      normal liver TRL 1215 cells. TRL 1215 cells were exposed for 20 weeks to MMAs(V),
      DMAs(V), or TMAs(V)O at levels that produced submicromolar cellular
      concentrations of arsenic. On chronic exposure to these methylated arsenicals,
      the cells acquired tolerance to acute arsenic cytolethality. Cellular arsenic
      uptake was reduced in these cells compared to passage-matched control cells. The
      long-term arsenic exposure increased glutathione S-transferase (GST) activity and
      cellular glutathione (GSH) levels. Glutathione S-transferase, multidrug
      resistance-associated proteins (Mrps; efflux transporters encoded by Mrp genes),
      and P-glycoprotein [P-gp; efflux transporter encoded by multidrug resistance gene
      (MDR)] had also increased in these cells at the transcript and protein levels.
      The depletion of cellular GSH and the inhibition of Mrps and P-gp functions
      increased cellular arsenic uptake and reduced arsenic tolerance in these cells.
      These results indicate that chronic exposure to methylated arsenicals induces a
      generalized arsenic tolerance that is caused by increased arsenic excretion.
      Because accumulation of methylated arsenicals may occur in patients with chronic
      arsenic poisoning and arsenic-treated APL patients, this study may provide
      important information regarding chronic arsenic poisoning and the latent risk of
      developing multidrug resistance in APL therapy using inorganic arsenite.

PMID- 16436461
TI  - Feasibility of imprint cytology for evaluation of mediastinal lymph nodes in lung
      cancer.
AB  - BACKGROUND: Intraoperative evaluation of mediastinal lymph nodes is a necessary
      step which helps us to decide whether or not to continue the operation of lung
      cancer. Imprint cytology (IC) can be used as an alternative method in staging. It
      is a more rapid and simpler procedure than frozen section (FS) analysis.
      Therefore, we compared the diagnostic accuracy of IC with permanent section on
      1050 mediastinal lymph nodes. METHODS: A total of 255 non-small cell lung cancer
      patients who underwent surgical procedure between January 1995 and April 2004
      were included. There were 236 males and 19 females with a mean age of 54.2 years
      (range 26-79 years). In order to obtain lymph node samples mediastinoscopy was
      performed in 232 (91%), anterior mediastinotomy in 50 (20%) and video-assisted
      thoracoscopic surgery in 16 (6.3%) patients. During final pathological diagnosis,
      both imprint and permanent section slides were compared. RESULTS: There were five
      false-positive and eight false-negative results. The sensitivity, specificity and
      the predictive values for positive and negative results were 93.1, 99.5, 95.6 and
      99.1%, respectively. The overall efficiency was 98.8%. CONCLUSIONS: The
      diagnostic IC is an accurate, reliable, simple and less time-consuming method for
      evaluation of mediastinal lymph nodes in lung cancer, compared with FS method.

PMID- 16436462
TI  - Neutropenic colitis during standard dose combination chemotherapy with nedaplatin
      and irinotecan for testicular cancer.
AB  - A 54-year-old man received combination chemotherapy with nedaplatin and
      irinotecan as salvage chemotherapy for refractory non-seminomatous testicular
      cancer. The patient developed abdominal pain and high fever on Day 21 after the
      initiation of chemotherapy. Computed tomography revealed thickening of the
      terminal ileum wall and paralytic ileus. The patient recovered with intensive
      supportive management including broad-spectrum antibiotics, bowel rest with
      gastric intubation and intravenous gamma-globulin. Neutropenic colitis has been
      thought to be a serious gastrointestinal complication associated with
      chemotherapy for hematological malignancy. The mortality rate is as high as 21
      48% according to a recent review. The present case indicates that the neutropenic
      colitis can occur under neutropenic conditions induced by the standard-dose
      chemotherapy for solid cancer.

PMID- 16436463
TI  - Intermediate dose 5-fluorouracil-induced encephalopathy.
AB  - As an acute neurotoxicity, high dose 5-fluorouracil (5-FU)-induced encephalopathy
      is well-known, but encephalopathy associated with lower dose is rarely reported.
      Here, we report a case of a male with anal cancer who was treated with 5-FU 1000
      mg/m(2), continuous infusion for 5 days q4 weeks. At the second and the fourth
      cycles of chemotherapy, sudden confusion, cognitive dysfunction and
      disorientation occurred during 5-FU infusion. They were accompanied by
      hyperammonemia in the absence of focal neurological deficits or structural
      abnormalities. These symptoms completely disappeared and the serum ammonia level
      returned to normal after discontinuation of 5-FU and conservative care. In order
      to investigate a possible deficit of dihydropyrimidine dehydrogenase (DPD), we
      checked its mRNA level before and after treatment using real-time PCR. The
      patient's pre-treatment level was 80% compared with reference group, and it was
      elevated up to 187% of initial after 5-FU treatment, implying that that his
      encephalopathy may be 5-FU catabolite type rather than DPD deficiency. In
      conclusion, we report that encephalopathy can develop even with the dose of 5-FU
      lower than ever reported, and it should be considered as a differential diagnosis
      for proper management.

PMID- 16436464
TI  - A role of TRAIL in killing osteoblasts by myeloma cells.
AB  - In multiple myeloma (MM), neoplastic plasma cells accumulate in the bone marrow
      where their survival, proliferation, and apoptosis are controlled at multiple
      levels by interaction with the bone marrow microenvironment. Myeloma cells
      actively control these interactions by activating stromal and endothelial cells
      for production of survival factors, such as interleukin-6, and suppressing other
      cell types such as erythroblasts, normal B cell progenitors, and T-cells. In the
      present study, we identified primary osteoblasts as additional potential targets
      for myeloma cell-mediated suppression which was partly dependent on the death
      receptor ligand TRAIL. Besides killing of osteoblasts, myeloma cell lines
      sensitized osteoblasts to cell death mediated by recombinant TRAIL, whereas
      primary osteoblasts protected myeloma cells from TRAIL-mediated apoptosis that
      was mediated by osteoprotegerin (OPG). Besides increase of osteoclastogenesis and
      osteoclast activity, suppression of bone-forming cells by myeloma cells might
      contribute to bone loss in MM patients. In addition, clinical development of
      recombinant TRAIL as anti-myeloma therapy should include evaluation of potential
      side effects on viability of normal bone cells.

PMID- 16436465
TI  - Premature aging-like phenotype in fibroblast growth factor 23 null mice is a
      vitamin D-mediated process.
AB  - Fibroblast growth factor 23 null mice (Fgf-23-/-) have a short lifespan and show
      numerous biochemical and morphological features consistent with premature aging
      like phenotypes, including kyphosis, severe muscle wasting, hypogonadism,
      osteopenia, emphysema, uncoordinated movement, T cell dysregulation, and atrophy
      of the intestinal villi, skin, thymus, and spleen. Furthermore, increased vitamin
      D activities in homozygous mutants are associated with severe atherosclerosis and
      widespread soft tissue calcifications; ablation of vitamin D activity from Fgf-23
      /- mice, by genetically deleting the 1alpha(OH)ase gene, eliminates
      atherosclerosis and ectopic calcifications and significantly rescues premature
      aging-like features of Fgf-23-/- mice, resulting in prolonged survival of Fgf-23
      /-/1alpha(OH)ase-/- double mutants. Our results indicate a novel role of Fgf-23
      in developing premature aging-like features through regulating vitamin D
      homeostasis. Finally, our data support a new model of interactions among Fgf-23,
      vitamin D, and klotho, a gene described as being associated with premature aging
      process.

PMID- 16436467
TI  - N-ethyl-N-nitrosourea (ENU) mutagenesis and male fertility research.
AB  - Male infertility affects about 1 in 25 men in the western world. Conversely,
      there is an urgent requirement for additional male-based contraceptives, yet
      progress in both areas has been severely hampered by a lack of knowledge of the
      biochemistry and physiology of male reproductive function. It is only through a
      thorough knowledge of these processes that we can hope to insightfully regulate
      male reproductive function. Without doubt, mouse models will form an important
      foundation in any future process. In recent years, the chemical mutagen N-ethyl-N
      nitrosourea (ENU) has been used widely to identify genes essential for a range of
      biological systems including male infertility. These studies have shown random
      mutagenesis is an attractive means of identifying key genes for male fertility.
      This technique has distinct, but complementary advantages compared to knockout
      technologies. Specifically, it allows the removal of researcher bias whereby only
      pre-conceived genes are tested for function; it produces mice with a guaranteed
      phenotype and allows for the production of allelic series of mice to dissect all
      aspects of gene function. ENU mouse mutagenesis programs will enable advances in
      the diagnosis and treatment of human male infertility and ultimately aid in the
      development of novel male-based contraceptives.

PMID- 16436466
TI  - Vascularized tissue-engineered chambers promote survival and function of
      transplanted islets and improve glycemic control.
AB  - We have developed a chamber model of islet engraftment that optimizes islet
      survival by rapidly restoring islet-extracellular matrix relationships and
      vascularization. Our aim was to assess the ability of syngeneic adult islets
      seeded into blood vessel-containing chambers to correct streptozotocin-induced
      diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel
      extracellular matrix were inserted into chambers based on either the splenic or
      groin (epigastric) vascular beds, or, in the standard approach, injected under
      the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an
      intraperitoneal glucose tolerance test performed at 6 weeks in the presence of
      the islet grafts. Relative to untreated diabetic animals, glycemic control
      significantly improved in all islet transplant groups, strongly correlating with
      islet counts in the graft (P<0.01), and with best results in the splenic chamber
      group. Glycemic control deteriorated after chambers were surgically removed at
      week 8. Immunohistochemistry revealed islets with abundant insulin content in
      grafts from all groups, but with significantly more islets in splenic chamber
      grafts than the other treatment groups (P<0.05). It is concluded that
      hyperglycemia in experimental type 1 diabetes can be effectively treated by
      islets seeded into a vascularized chamber functioning as a "pancreatic organoid."

PMID- 16436468
TI  - Oxytocin--its role in male reproduction and new potential therapeutic uses.
AB  - Oxytocin (OT) is traditionally thought of as a "female" neurohypophysis hormone
      due to its role in parturition and milk ejection. However, OT is recognized as
      having endocrine and paracrine roles in male reproduction. At ejaculation, a
      burst of OT is released from the neurohypophysis into the systemic circulation
      and stimulates contractions of the reproductive tract aiding sperm release. There
      is conclusive evidence that OT is synthesized within the mammalian testis,
      epididymis and prostate and the presence of OT receptors (OTRs) through the
      reproductive tract supports a local action for this peptide. OT has a paracrine
      role in stimulating contractility of the seminiferous tubules, epididymis and the
      prostate gland. Interestingly, OT has also been shown to modulate androgen levels
      in these tissues via stimulation of the conversion of testosterone to
      dihydrotestostone (DHT) by 5alpha-reductase. The elucidation of OT's role in male
      reproduction has suggested a number of potential therapeutic uses for this
      hormone. Exogenous administration of OT has, in some cases, been shown to
      increase the numbers of ejaculated sperm, possibly by stimulating contractions of
      the reproductive tract and thus aiding sperm passage. Within the prostate, OT has
      been shown to affect gland growth both directly and via its interaction with
      androgen metabolism. Prostate pathologies due to unregulated cell
      proliferation/growth, such as benign prostatic hyperplasia and cancer, are
      unfortunately very common and few effective treatments are available. Greater
      understanding of paracrine growth mediators, such as OT, is likely to provide new
      mechanisms for treating such pathologies.

PMID- 16436469
TI  - Expression of beta-catenin is necessary for physiological growth of adult
      skeletal muscle.
AB  - Expression of beta-catenin is known to be important for developmental processes
      such as embryonic pattern formation and determination of cell fate. Inappropriate
      expression, however, has been linked to pathological states such as cancer. Here
      we report that expression of beta-catenin is necessary for physiological growth
      of skeletal muscle in response to mechanical overload. Conditional inactivation
      of beta-catenin was induced in control and overloaded muscle through
      intramuscular injection of adenovirus expressing Cre recombinase in beta-catenin
      floxed mice. Individual muscle fiber analysis was performed to identify
      positively transfected/inactivated cells and determine fiber cross-sectional
      area. The results demonstrate that fiber growth is completely inhibited when the
      beta-catenin expression is lost. This effect was cell autonomous, as fibers that
      did not exhibit recombination in the floxed mice grew to the same magnitude as
      infected/noninfected fibers from wild-type mice. These findings suggest that beta
      catenin may be a primary molecular site through which multiple signaling pathways
      converge in regulating physiological growth.

PMID- 16436470
TI  - Glutamine's protection against cellular injury is dependent on heat shock factor
      1.
AB  - Glutamine (GLN) has been shown to protect cells, tissues, and whole organisms
      from stress and injury. Enhanced expression of heat shock protein (HSP) has been
      hypothesized to be responsible for this protection. To date, there are no clear
      mechanistic data confirming this relationship. This study tested the hypothesis
      that GLN-mediated activation of the HSP pathway via heat shock factor-1 (HSF-1)
      is responsible for cellular protection. Wild-type HSF-1 (HSF-1(+/+)) and knockout
      (HSF-1(-/-)) mouse fibroblasts were used in all experiments. Cells were treated
      with GLN concentrations ranging from 0 to 16 mM and exposed to heat stress injury
      in a concurrent treatment model. Cell viability was assayed with phenazine
      methosulfate plus tetrazolium salt, HSP-70, HSP-25, and nuclear HSF-1 expression
      via Western blot analysis, and HSF-1/heat shock element (HSE) binding via EMSA.
      GLN significantly attenuated heat-stress induced cell death in HSF-1(+/+) cells
      in a dose-dependent manner; however, the survival benefit of GLN was lost in HSF
      1(-/-) cells. GLN led to a dose-dependent increase in HSP-70 and HSP-25
      expression after heat stress. No inducible HSP expression was observed in HSF-1(
      /-) cells. GLN increased unphosphorylated HSF-1 in the nucleus before heat
      stress. This was accompanied by a GLN-mediated increase in HSF-1/HSE binding and
      nuclear content of phosphorylated HSF-1 after heat stress. This is the first
      demonstration that GLN-mediated cellular protection after heat-stress injury is
      related to HSF-1 expression and cellular capacity to activate an HSP response.
      Furthermore, the mechanism of GLN-mediated protection against injury appears to
      involve an increase in nuclear HSF-1 content before stress and increased HSF-1
      promoter binding and phosphorylation.

PMID- 16436471
TI  - G protein-coupled receptors serve as mechanosensors for fluid shear stress in
      neutrophils.
AB  - Many cells respond to fluid shear stress but in a cell type-specific fashion.
      Fluid shear stress applied to leukocytes serves to control pseudopod formation,
      migration, and other functions. Specifically, fresh neutrophils or neutrophilic
      leukocytes derived from differentiated HL60 cells respond to fluid shear stress
      by cytoplasmic pseudopod retraction. The membrane elements that sense fluid shear
      and induce such a specific response are still unknown, however. We hypothesized
      that membrane receptors may serve as fluid shear sensors. We found that fluid
      shear decreased the constitutive activity of G protein-coupled receptors (GPCRs).
      Inhibition of GPCR constitutive activity by inverse agonists abolished fluid
      shear stress-induced cell area reduction. Among the GPCRs in neutrophils, the
      formyl peptide receptor (FPR) exhibits relatively high constitutive activity.
      Undifferentiated HL60 cells that lacked FPR formed few pseudopods and showed no
      detectable response to fluid shear stress, whereas expression of FPR in
      undifferentiated HL60 cells caused pseudopod projection and robust pseudopod
      retraction during fluid shear. FPR small interfering RNA-transfected
      differentiated HL60 cells exhibited no response to fluid shear stress. These
      results suggest that GPCRs serve as mechanosensors for fluid shear stress in
      neutrophils by decreasing its constitutive activity and reducing pseudopod
      projection.

PMID- 16436472
TI  - Adenosine stimulates depolarization and rise in cytoplasmic [Ca2+] in type I
      cells of rat carotid bodies.
AB  - During hypoxia, the level of adenosine in the carotid bodies increases as a
      result of ATP catabolism and adenosine efflux via adenosine transporters. Using
      Ca2+ imaging, we found that adenosine, acting via A2A receptors, triggered a rise
      in cytoplasmic [Ca2+] ([Ca2+]i) in type I (glomus) cells of rat carotid bodies.
      The adenosine response could be mimicked by forskolin (but not its inactive
      analog), and could be abolished by the PKA inhibitor H89. Simultaneous
      measurements of membrane potential (perforated patch recording) and [Ca2+]i
      showed that the adenosine-mediated [Ca2+]i rise was accompanied by
      depolarization. Ni2+, a voltage-gated Ca2+ channel (VGCC) blocker, abolished the
      adenosine-mediated [Ca2+]i rise. Although adenosine was reported to inhibit a 4
      aminopyridine (4-AP)-sensitive K+ current, 4-AP failed to trigger any [Ca2+]i
      rise, or to attenuate the adenosine response. In contrast, anandamide, an
      inhibitor of the TWIK-related acid-sensitive K+-1 (TASK-1) channels, triggered
      depolarization and [Ca2+]i rise. The adenosine response was attenuated by
      anandamide but not by tetraethylammonium. Our results suggest that adenosine,
      acting via the adenylate cyclase and PKA pathways, inhibits the TASK-1 K+
      channels. This leads to depolarization and activation of Ca2+ entry via VGCC.
      This excitatory action of adenosine on type I cells may contribute to the
      chemosensitivity of the carotid body during hypoxia.

PMID- 16436473
TI  - PKC-delta mediates activation of ERK1/2 and induction of iNOS by IL-1beta in
      vascular smooth muscle cells.
AB  - Although the inflammatory cytokine interleukin-1beta (IL-beta) is an important
      regulator of gene expression in vascular smooth muscle (VSM), the signal
      transduction pathways leading to transcriptional activation upon IL-1beta
      stimulation are poorly understood. Recent studies have implicated IL-1beta
      mediated ERK1/2 activation in the upregulation of type II nitric oxide synthase
      (iNOS) in VSM. We report that these events are mediated in a phospholipase C
      (PLC)- and protein kinase C (PKC)-delta-dependent manner utilizing a signaling
      mechanism independent of p21(ras) (Ras) and Raf1 activation. Stimulation of rat
      aortic VSM cells with IL-1beta activated PLC-gamma and pharmacological inhibition
      of PLC attenuated IL-1beta-induced ERK1/2 activation and subsequent iNOS
      expression. Stimulation with IL-1beta activated PKC-alpha and -delta, which was
      blocked using the PLC inhibitor U-73122. Pharmacological studies using isoform
      specific PKC inhibitors and adenoviral overexpression of constitutively active
      PKC-delta indicated that ERK1/2 activation was PKC-alpha independent and PKC
      delta dependent. Similarly, adenoviral overexpression of constitutively activated
      PKC-delta enhanced iNOS expression. IL-1beta stimulation did not induce either
      Ras or Raf1 activity. The absence of a functional role for Ras and Raf1 related
      to ERK1/2 activation and iNOS expression was further confirmed by adenoviral
      overexpression of dominant-negative Ras and treatment with the Raf1 inhibitor
      GW5074. Taken together, we have outlined a novel transduction pathway implicating
      PKC-delta as a critical component of the IL-1-dependent activation of ERK in VSM
      cells.

PMID- 16436474
TI  - Cultured slow vs. fast skeletal muscle cells differ in physiology and
      responsiveness to stimulation.
AB  - In vitro studies have used protein markers to distinguish between myogenic cells
      isolated from fast and slow skeletal muscles. The protein markers provide some
      support for the hypothesis that satellite cells from fast and slow muscles are
      different, but the data are equivocal. To test this hypothesis directly, three
      dimensional skeletal muscle constructs were engineered from myogenic cells
      isolated from fast tibialis anterior (TA) and slow soleus (SOL) muscles of rats
      and functionality was tested. Time to peak twitch tension (TPT) and half
      relaxation time (RT(1/2)) were approximately 30% slower in constructs from the
      SOL. The slower contraction and relaxation times for the SOL constructs resulted
      in left shift of the force-frequency curve compared with those from the TA.
      Western blot analysis showed a 60% greater quantity of fast myosin heavy chain in
      the TA constructs. 14 days of chronic low-frequency electrical stimulation
      resulted in a 15% slower TPT and a 14% slower RT(1/2), but no change in absolute
      force production in the TA constructs. In SOL constructs, slow electrical
      stimulation resulted in an 80% increase in absolute force production with no
      change in TPT or RT(1/2). The addition of cyclosporine A did not prevent the
      increase in force in SOL constructs after chronic low-frequency electrical
      stimulation, suggesting that calcineurin is not responsible for the increase in
      force. We conclude that myogenic cells associated with a slow muscle are
      imprinted to produce muscle that contracts and relaxes slowly and that
      calcineurin activity cannot explain the response to a slow pattern of electrical
      stimulation.

PMID- 16436475
TI  - Beta2 and beta4 subunits of BK channels confer differential sensitivity to acute
      modulation by steroid hormones.
AB  - Membrane-associated receptors for rapid, steroidal neuromodulation remain
      elusive. Estradiol has been reported to facilitate activation of voltage- and
      Ca(2+)-dependent BK potassium channels encoded by Slo, if associated with beta1
      subunits. We show here that 1) multiple members of the beta family confer
      sensitivity to multiple steroids on BK channels, 2) that beta subunits
      differentiate between steroids, and 3) that different betas have distinct
      relative preferences for particular steroids. Expressed in HEK 293 cells, inside
      out patches with channels composed of Slo-alpha alone showed no steroid
      sensitivity. Cells expressing alphabeta4 exhibited potent, rapid, reversible, and
      dose-dependent potentiation by corticosterone (CORT; a glucocorticoid), and were
      potentiated to a lesser degree by other sex and stress steroids. In contrast,
      alphabeta2 channels were potentiated more strongly by dehydroepiandrosterone
      (DHEA; an enigmatic, stress-related adrenal androgen), and to a lesser extent by
      CORT, estradiol, testosterone, and DHEA-S. Cholesterol had no effect on any BK
      channel compositions tested. Conductance-voltage plots of channels composed of
      alpha plus beta2 or beta4 subunits were shifted in the negative direction by
      steroids, indicating greater activation at negative voltages. Thus our results
      argue that the variety of Slo-beta subunit coexpression patterns occurring in
      vivo expands the repertoire of Slo channel gating in yet another dimension not
      fully appreciated, rendering BK gating responsive to dynamic fluctuations in a
      multiple of steroid hormones.

PMID- 16436476
TI  - Representation of auditory signals in the M-cell: role of electrical synapses.
AB  - The teleost Mauthner (M-) cell mediates a sound-evoked escape behavior. A major
      component of the auditory input is transmitted by large myelinated club endings
      of the posterior VIIIth nerve. Paradoxically, although nerve stimulations
      revealed these afferents have mixed electrical and glutamatergic synapses on the
      M-cell's distal lateral dendrite, paired pre- and postsynaptic recordings
      indicated most individual connections are chemically silent. To determine the
      sensory information encoded and the relative contributions of these two
      transmission modes, M-cell responses to acoustic stimuli in air were recorded
      intracellularly. Excitatory postsynaptic potentials (EPSPs) evoked by both short
      100- to 900-Hz "pips" and longer-lasting amplitude- and frequency-modulated
      sounds were dominated by fast, repetitive EPSPs superimposed on an underlying
      slow depolarization. Fast EPSPs 1) have kinetics comparable to presynaptic action
      potentials, 2) are maximal on the distal lateral dendrite, and 3) are insensitive
      to GluR antagonists. They presumably are coupling potentials, and power spectral
      analysis indicated they constitute a high-pass signal that accurately tracks
      sound frequency and amplitude. The spatial profile of the slow EPSP suggests both
      proximal and distal dendritic sources, a result supported by predictions of a
      multicompartmental model and the effects of AMPAR antagonists, which
      preferentially reduced the proximal component. Thus a second class of afferents
      generates a portion of the slow EPSP that, with sound stimuli, demonstrate that
      the dominant mode of transmission at LMCE synapses is electrical. The slow EPSP
      is a dynamic, low-pass representation of stimulus strength. Accordingly,
      amplitude and phase information, which are segregated in other systems, are
      faithfully represented in the M-cell.

PMID- 16436478
TI  - Contralateral white noise selectively changes left human auditory cortex activity
      in a lexical decision task.
AB  - In a previous study, we hypothesized that the approach of presenting information
      bearing stimuli to one ear and noise to the other ear may be a general strategy
      to determine hemispheric specialization in auditory cortex (AC). In that study,
      we confirmed the dominant role of the right AC in directional categorization of
      frequency modulations by showing that fMRI activation of right but not left AC
      was sharply emphasized when masking noise was presented to the contralateral ear.
      Here, we tested this hypothesis using a lexical decision task supposed to be
      mainly processed in the left hemisphere. Subjects had to distinguish between
      pseudowords and natural words presented monaurally to the left or right ear
      either with or without white noise to the other ear. According to our hypothesis,
      we expected a strong effect of contralateral noise on fMRI activity in left AC.
      For the control conditions without noise, we found that activation in both
      auditory cortices was stronger on contralateral than on ipsilateral word
      stimulation consistent with a more influential contralateral than ipsilateral
      auditory pathway. Additional presentation of contralateral noise did not
      significantly change activation in right AC, whereas it led to a significant
      increase of activation in left AC compared with the condition without noise. This
      is consistent with a left hemispheric specialization for lexical decisions. Thus
      our results support the hypothesis that activation by ipsilateral information
      bearing stimuli is upregulated mainly in the hemisphere specialized for a given
      task when noise is presented to the more influential contralateral ear.

PMID- 16436477
TI  - Cortico-cortical interactions in spatial attention: A combined ERP/TMS study.
AB  - To gain insight into the neural basis of visual attention, we combined
      transcranial magnetic stimulation (TMS) and event-related potentials (ERPs)
      during a visual search task. Single-pulse TMS over right posterior parietal
      cortex (rPPC) delayed response times to targets during conjunction search, and
      this behavioral effect had a direct ERP correlate. The early phase of the N2pc
      component that reflects the focusing of attention onto target locations in a
      search display was eliminated over the right hemisphere when TMS was applied
      there but was present when TMS was delivered to a control site (vertex). This
      finding demonstrates that rPPC TMS interferes with attentional selectivity in
      remote visual areas.

PMID- 16436479
TI  - Electrical stimulation of mammalian retinal ganglion cells with multielectrode
      arrays.
AB  - Existing epiretinal implants for the blind are designed to electrically stimulate
      large groups of surviving retinal neurons using a small number of electrodes with
      diameters of several hundred micrometers. To increase the spatial resolution of
      artificial sight, electrodes much smaller than those currently in use are
      desirable. In this study, we stimulated and recorded ganglion cells in isolated
      pieces of rat, guinea pig, and monkey retina. We used microfabricated hexagonal
      arrays of 61 platinum disk electrodes with diameters between 6 and 25 microm,
      spaced 60 microm apart. Charge-balanced current pulses evoked one or two spikes
      at latencies as short as 0.2 ms, and typically only one or a few recorded
      ganglion cells were stimulated. Application of several synaptic blockers did not
      abolish the evoked responses, implying direct activation of ganglion cells.
      Threshold charge densities were typically <0.1 mC/cm2 for a pulse duration of 100
      micros, corresponding to charge thresholds of <100 pC. Stimulation remained
      effective after several hours and at high frequencies. To show that closely
      spaced electrodes can elicit independent ganglion cell responses, we used the
      multielectrode array to stimulate several nearby ganglion cells simultaneously.
      From these data, we conclude that electrical stimulation of mammalian retina with
      small-diameter electrode arrays is achievable and can provide high temporal and
      spatial precision at low charge densities. We review previous epiretinal
      stimulation studies and discuss our results in the context of 32 other
      publications, comparing threshold parameters and safety limits.

PMID- 16436480
TI  - Is equilibrium point control feasible for fast goal-directed single-joint
      movements?
AB  - Several types of equilibrium point (EP) controllers have been proposed for the
      control of posture and movement. EP controllers are appealing from a
      computational perspective because they do not require solving the "inverse
      dynamic problem" (i.e., computation of the torques required to move a system
      along a desired trajectory). It has been argued that EP controllers are not
      capable of controlling fast single-joint movements. To refute this statement,
      several extensions have been proposed, although these have been tested using
      models in which only the tendon compliance, force-length-velocity relation, and
      mechanical interaction between tendon and contractile element were not adequately
      represented. In the present study, fast elbow-joint movements were measured and
      an attempt was made to reproduce these using a realistic musculoskeletal model of
      the human arm. Three types of EP controllers were evaluated: an open-loop alpha
      controller, a closed-loop lambda-controller, and a hybrid open- and closed-loop
      controller. For each controller we considered a continuous version and a version
      in which the control signals were sent out intermittently. Only the intermittent
      hybrid EP controller was capable of generating movements that were as fast as
      those of the subjects. As a result of the nonlinear muscle properties, the hybrid
      EP controller requires a more detailed representation of static muscle properties
      than generally assumed in the context of EP control. In sum, this study shows
      that fast single-joint movements can be realized without explicitly solving the
      inverse dynamics problem, but in a less straightforward manner than implied by
      proponents of conventional EP controllers.

PMID- 16436481
TI  - Physiological and anatomical properties of mouse medial vestibular nucleus
      neurons projecting to the oculomotor nucleus.
AB  - Neurons in the medial vestibular nucleus (MVN) vary in their projection patterns,
      responses to head movement, and intrinsic firing properties. To establish whether
      neurons that participate in the vestibulo-ocular reflex (VOR) have distinct
      intrinsic physiological properties, oculomotor nucleus (OMN)-projecting neurons
      were identified in mouse brainstem slices by fluorescent retrograde labeling from
      the oculomotor complex and targeted for patch-clamp recordings. Such neurons were
      located in the magnocellular portion of the MVN contralateral to tracer
      injection, were mostly multipolar, and had soma diameters of around 20 mum. They
      fired spontaneous action potentials at rates higher than those of other MVN
      neurons and their spikes were of unusually short duration. OMN-projecting neurons
      responded to 1-s intracellular current injection with exceptionally high firing
      rates of >500 spikes/s. Their current-firing relationship was highly linear, with
      weak firing response adaptation during steady depolarization and little
      postinhibitory rebound firing after membrane hyperpolarization. Their firing
      responses were approximately in phase with sinusoidal current injection. The
      response dynamics of OMN-projecting neurons could be simulated with a simple
      integrate-and-fire model modified with the addition of small adaptation and
      rebound conductances. These findings indicate that the membrane properties of OMN
      projecting neurons allow them to respond to head movements reliably and with high
      sensitivity but without substantially altering input dynamics.

PMID- 16436482
TI  - Distinct transmitter release properties determine differences in short-term
      plasticity at functional and silent synapses.
AB  - Recent evidence suggests that functional and silent synapses are not only
      postsynaptically different but also presynaptically distinct. The presynaptic
      differences may be of functional importance in memory formation because a
      proposed mechanism for long-term potentiation is the conversion of silent
      synapses into functional ones. However, there is little direct experimentally
      evidence of these differences. We have investigated the transmitter release
      properties of functional and silent Schaffer collateral synapses and show that on
      the average functional synapses displayed a lower percentage of failures and
      higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at
      +60 mV. Moreover, functional but not silent synapses show paired-pulse
      facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be
      distinct in the two types of synapse. We examined whether intraterminal
      endoplasmic reticulum Ca2+ stores influenced the release properties of these
      synapses. Ryanodine (100 microM) and thapsigargin (1 microM) increased the
      percentage of failures and decreased both the EPSC amplitude and PPF in
      functional synapses. Caffeine (10 mM) had the opposite effects. In contrast,
      silent synapses were insensitive to both ryanodine and caffeine. Hence we have
      identified differences in the release properties of functional and silent
      synapses, suggesting that synaptic terminals of functional synapses express
      regulatory molecular mechanisms that are absent in silent synapses.

PMID- 16436483
TI  - Galvanic vestibular stimulation modifies vection paths in healthy subjects.
AB  - The present study aimed at determining whether vestibular inputs contribute to
      the perception of the direction of self-motion. This question was approached by
      investigating the effects of binaural bipolar galvanic vestibular stimulation
      (GVS) on visually induced self-motion (i.e., vection) in healthy subjects.
      Stationary seated subjects were submitted to optokinetic stimulation inducing
      either forward or upward linear vection. While perceiving vection, they were
      administered trapezoidal GVS of different intensities and ramp durations.
      Subjects indicated the shape and direction of their perceived self-motion path
      throughout the experiment by a joystick, and after each trial by the manipulation
      of a 3D mannequin. Results show that: 1) GVS induced alterations of the path of
      vection; 2) these alterations occurred more often after GVS onset than after GVS
      offset; 3) the occurrence of vection path alterations after GVS onset depended on
      the intensity of GVS but not on the steepness of the GVS variation; 4) the
      vection path deviated laterally according to either an oblique or a curved path;
      and 5) the vection path deviated toward the cathode side after GVS onset. It is
      the first time that vestibular information, already known to contribute to the
      induction of vection, is shown to modify self-motion perception during the course
      of vection.

PMID- 16436484
TI  - Quadriceps H-reflex modulation during pedaling.
AB  - The main aims of this study were 1) to investigate possible phase-, speed-, and
      task-dependent changes in the quadriceps H-reflex during pedaling, and to achieve
      this, 2) to develop an optimized H-reflex recording and processing procedure for
      recording of quadriceps H-reflexes during movement. It was hypothesized that the
      behavior of the quadriceps H-reflex concerning phase, speed, and task dependency
      corresponds to the behavior of the soleus H-reflex during rhythmical leg
      movements. The applied H-reflex procedure appeared to be reliable for obtaining
      the quadriceps H-reflex modulation during leg movement. The vastus lateralis (VL)
      and rectus femoris (RF) H-reflexes showed a phase-dependent modulation during
      pedaling at a frequency of 80 rpm with almost parallel changes in the reflex
      amplitude and motor recruitment level. However, when the speed of movement was
      reduced from 80 to 40 revolutions per minute (rpm) and crank load simultaneously
      increased (i.e., a halving of the movement speed with a constant motor
      recruitment level), the quadriceps H-reflex modulation pattern changed
      significantly in relation to the pattern of motor recruitment, i.e., at 40 rpm,
      the reflex excitability remained high during a gradual derecruitment during power
      generation in downstroke. Comparison of the "operationally defined H-reflex gain
      function" obtained during 1) pedaling at 80 rpm and 2) isometric quadriceps
      contractions in sitting position showed no significant task-dependent changes in
      the quadriceps H-reflex. Consequently, the hypothesis was only partly
      corroborated, and the findings indicate differences in the neural control of the
      soleus and the quadriceps muscle during rhythmical movements.

PMID- 16436485
TI  - Combining correlation and interference methods in the human brain. Focus on
      "Cortico-cortical interactions in spatial attention: A combined ERP/TMS study".

PMID- 16436486
TI  - A research agenda for patient safety.

PMID- 16436487
TI  - The contribution of qualitative approaches to musculoskeletal research.

PMID- 16436488
TI  - Treatment of rheumatoid arthritis with ornidazole. A randomized, double-blind,
      placebo-controlled study.

PMID- 16436489
TI  - Continuation of treatment with infliximab in ankylosing spondylitis: 2-yr open
      follow-up.
AB  - OBJECTIVE: To evaluate the continuation and safety of treatment with infliximab
      in ankylosing spondylitis (AS) over a 2-yr period. METHODS: This study was an
      open, observational, 2-yr extension study of an open-label study of three
      induction infusions of infliximab in refractory AS. The fourth infusion was
      performed only in case of relapse. Thereafter, infliximab was to be administered
      as needed according to the rheumatologist's opinion; however, for some patients,
      infusions were performed systematically. RESULTS: None of the 50 recruited
      patients was lost to follow-up. Thirteen patients (26%) interrupted their
      treatment by infliximab: four for inefficacy, seven for adverse events, of which
      four were for allergic reactions to the infusion, and two for other reasons. For
      all of the 46 patients who had had three infusions judged efficacious and well
      tolerated, a fourth infusion was performed because of a flare of the disease,
      after a mean interval of 20.3+/-9.9 weeks (range 7.3-57.9). Over the 24 months,
      the mean interval between infusions was 11.6+/-9.0 weeks. This interval was
      longer when patients were treated only as needed (mean 14.3+/-12.1 weeks) than
      systematically (mean 9.8+/-5.7 weeks). Side-effects were similar to those noted
      in shorter-term studies; seven patients suffered serious adverse events. There
      were no deaths, no malignancies and no tuberculosis. CONCLUSION: This study
      confirms the long-term treatment continuation of infliximab in AS, and shows an
      acceptable safety profile. It appears that for some patients the disease can be
      controlled with long intervals between infusions; these findings warrant further
      studies.

PMID- 16436491
TI  - Bronchogenic carcinoma associated with rheumatoid arthritis: role of FDG-PET
      scans.

PMID- 16436490
TI  - Risk factors for dysbaric osteonecrosis.
AB  - OBJECTIVES: Dysbaric osteonecrosis (DON) is a complication of ineffective
      decompression following exposure to high-pressure environments. This study was
      designed to determine risk factors for the occurrence of DON in divers. METHODS:
      Fifty-six male divers received skeletal examinations by radiography to assess the
      occurrence of DON. A questionnaire was used to obtain clinical and diving
      information, including diving experience and maximum diving depth. Blood samples
      were collected to analyse the levels of plasminogen activator inhibitor (PAI)-1,
      cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein,
      high-density lipoprotein, apolipoprotein A1 and apolipoprotein B. RESULTS:
      Lesions of DON were detected in 31 of the 56 (55%) divers. Multivariate logistic
      regression analysis showed that high levels of PAI-1, a coagulation marker (odds
      ratio 4.281; P=0.0296) and great maximum diving depth (odds ratio 5.627;
      P=0.0231) were independent predictors of DON. CONCLUSIONS: This study has shown
      the presence of coagulation abnormality in divers with DON. This result suggests
      that a pharmacological approach incorporating the use of an anticoagulant may
      represent a potential strategy for the prevention of DON.

PMID- 16436492
TI  - The effect of infliximab on bone metabolism markers in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: The aim of this study was to evaluate urinary excretion of N
      telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), markers of bone
      resorption, and serum bone alkaline phosphatase (BAP) level, a marker of bone
      formation and an early marker of osteoblast differentiation, in patients with
      rheumatoid arthritis (RA) treated with infliximab. METHODS: Seventeen male and
      female patients (age 60.7+/-2.53 yr; mean disease duration 12.9+/-3.01 yr;
      Steinbrocker's class II-IV) with RA, diagnosed according to the criteria of the
      American College of Rheumatology (ACR), took part in the study between March 2003
      and January 2005. None of the patients had a history of oestrogen replacement
      therapy. All patients were treated with infliximab combined with methotrexate.
      Infliximab was infused intravenously at 3 mg/kg at baseline, 2 and 6 weeks, then
      every 8 weeks. To evaluate disease activity, ESR, CRP, the numbers of swollen and
      tender joints, modified Stanford Health Assessment Questionnaire (mHAQ) score and
      ACR score were measured. Levels of NTX and DPD in urine and BAP in serum were
      measured in all patients. RESULTS: ESR, CRP, the number of swollen joints and
      tender joints, and mHAQ score had decreased significantly 6 weeks after initial
      treatment and were still low 6 months after initial treatment. NTX levels had
      decreased significantly 6 weeks after the initial treatment and were still low 6
      months after initial treatment. DPD levels had decreased 6 months after initial
      infusion. Mean serum BAP level did not differ significantly among the three time
      points. NTX levels were statistically corresponding with the number of swollen
      joints and mHAQ scores. DPD levels were statistically lower corresponding with
      ESR. CONCLUSION: Infliximab therapy may inhibit generalized bone loss in patients
      with RA. NTX is a more sensitive marker than DPD.

PMID- 16436493
TI  - Vascular endothelial growth factor a signaling in the podocyte-endothelial
      compartment is required for mesangial cell migration and survival.
AB  - The glomerular filtration barrier separates the blood from the urinary space and
      consists of two major cell types: podocytes and fenestrated endothelial cells.
      Mesangial cells sit between the capillary loops and provide structural support.
      Proliferation and loss of mesangial cells both are central findings in a number
      of renal diseases, including diabetic nephropathy and mesangiolysis,
      respectively. Using cell-specific gene targeting, it was shown previously that
      vascular endothelial growth factor A (VEGF-A) production by podocytes is required
      for glomerular endothelial cell migration, differentiation, and survival. For
      further investigation of the effect of gene dose and VEGF-A knockdown within the
      glomerulus, mice that carry one hypomorphic VEGF-A allele and one podocyte
      specific null VEGF-A allele (VEGFhypo/loxP,Neph-Cre+/-) were generated; in these
      mice, the "allelic dose" of VEGF-A is intermediate between glomerular-specific
      heterozygous and null states. VEGFhypo/loxP,Neph-Cre+/- mice die at 3 wk of age
      from renal failure. Although endothelial cell defects are observed, striking loss
      of mesangial cells occurs postnatally. In addition, differentiated mesangial
      cells cannot be found in glomeruli of podocyte-specific null VEGF-A mice
      (VEGFloxP/loxP,Cre+/-). Together, these results demonstrate a key role for VEGF-A
      production in the podocyte for mesangial cell survival and differentiation.

PMID- 16436494
TI  - Uncoupling of vascular endothelial growth factor with nitric oxide as a mechanism
      for diabetic vasculopathy.
AB  - The role of VEGF in vascular disease is complicated. Vascular endothelial growth
      factor (VEGF) expression can be deleterious in diabetic vasculopathy, especially
      in kidney and retina. In contrast, VEGF seems to be renoprotective in nondiabetic
      renal disease. VEGF exerts it biologic effects in association with nitric oxide
      (NO), yet it is known that NO bioavailability is reduced in diabetes. Thus, it
      was hypothesized that this diverse biologic effect of VEGF on diabetic
      vasculopathy is due to uncoupling of VEGF with NO. VEGF stimulated NO production
      in a dose-dependent manner in bovine aortic endothelial cells (BAEC), and this
      was inhibited by either high glucose or Nomega-nitro-l-arginine methyl ester (L
      NAME) treatment. Endothelial NO synthase phosphorylation by VEGF was also
      inhibited by high glucose. It is interesting that both high glucose and L-NAME
      enhanced the proliferative response of endothelial cells, which was prevented by
      an NO donor. Furthermore, high glucose as well as L-NAME stimulated VEGF and
      kinase-insert domain receptor (KDR) (VEGF receptor 2) mRNA expression in BAEC.
      These data suggest that the uncoupling of VEGF with NO enhances endothelial cell
      proliferation via the KDR pathway. Compatible with these findings, a KDR
      antagonist blocked this response. In addition, a VEGF mutant, which binds only
      KDR, induced extracellular signal-regulated kinase (ERK) activation, and
      inhibition of ERK completely blocked endothelial cell proliferation under this
      condition, suggesting a role of the KDR-ERK1/2 pathway on endothelial cell
      proliferation. In conclusion, high glucose causes an uncoupling of VEGF with NO,
      which enhances endothelial cell proliferation via activation of the KDR-ERK1/2
      pathway. These results may provide new insights into the understanding of the
      mechanism of diabetic vascular disease.

PMID- 16436496
TI  - Cannabinoid-mediated elevation of intracellular calcium: a structure-activity
      relationship.
AB  - This laboratory has reported previously that Delta(9)-tetrahydrocannabinol
      (Delta(9)-THC) and cannabinol (CBN) robustly elevate intracellular calcium
      ([Ca(2+)](i)) in resting human and murine T cells, whereas CP55,940 [5-(1,1
      dimethylheptyl)-2-(5-hydroxy-2-(3-hydroxypropyl)cyclohexyl)phenol], a high
      affinity ligand for CB1 and CB2, does not. In light of our previous studies, the
      objective of the present investigation was to examine the ability of various
      cannabinoid compounds to elevate [Ca(2+)](i) in the CB2 receptor-expressing human
      peripheral blood acute lymphoid leukemia T cell line and the dependence of
      structural similarity to Delta(9)-THC therein. The present studies demonstrate
      that CBN and HU-210 [(6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6
      dimethyl-6H-dibenzo[b,d]pyran-9-methanol], both tricyclic and in that respect
      structurally similar to Delta(9)-THC, elevate [Ca(2+)](i). The [Ca(2+)](i)
      elevation elicited by both CBN and HU-210 was attenuated upon removal of
      extracellular calcium and upon pretreatment with SK&F96365 [1-[beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole], an inhibitor of
      receptor-operated cation channels. In addition, pretreatment with either CB1 or
      CB2 receptor antagonists attenuated the CBN- and HU-210-mediated [Ca(2+)](i)
      elevation. Further investigation of the dependence of Delta(9)-THC, CBN, and HU
      210 on cannabinoid receptors using splenocytes from wild-type and CB1(-/-)/CB2(-/
      ) mice showed that the [Ca(2+)](i) elevation elicited by all three tricyclic
      cannabinoids was independent of CB1 and CB2. Moreover, both the CB1 and CB2
      receptor antagonists attenuated that rise in [Ca(2+)](i) elicited by the
      tricyclic cannabinoids in the wild-type and CB1(-/-)/CB2(-/-) mouse splenocytes.
      Taken together, the present results demonstrate that classic tricyclic
      cannabinoids with structural similarity to Delta(9)-THC elicit a robust influx of
      calcium in T cells putatively through receptor-operated cation channels in a
      manner sensitive to the cannabinoid receptor antagonists, but independent of the
      CB1 and CB2 receptors.

PMID- 16436495
TI  - Endometrial chemokines, uterine natural killer cells and mast cells in long-term
      users of the levonorgestrel-releasing intrauterine system.
AB  - OBJECTIVE: The objective was to assess endometrial chemokines in users of the
      levonorgestrel-releasing intrauterine system (LNG-IUS) and correlate them with
      leucocyte populations, uterine natural killer cells (uNK) and mast cells (MCs).
      MATERIALS AND METHODS: Endometrium was obtained from two groups of women who had
      been using LNG-IUS for 3 years or more: 11 amenorrhoeic women formed the non
      bleeding group and 15 women who maintained some form of cyclic bleeding comprised
      the bleeding group. Specific antibodies were used for the assessment of
      neutrophils, uNK cells and MCs. Immunohistochemistry was performed to locate the
      chemokines 6Ckine and interleukin-8 (IL-8). RESULTS: Neutrophils were few and
      without differences between the two groups. uNK cells were significantly higher
      in the bleeding group (P < 0.0001). There was no difference between the total
      number of MCs and activated MCs, but there was a greater extracellular area
      stained for MC tryptase (P < 0.05). Chemokines 6CKine and IL-8 were abundant in
      the stroma and in the epithelium, and there was no difference between the groups.
      CONCLUSIONS: We observed more uNK cells in users with bleeding and a greater
      extracellular area stained for MC tryptase, although there were no differences
      between the number of MCs and activated MCs or the chemokines 6CKine and IL-8.
      uNK cells and MC products may play a role in provoking breakthrough bleeding in
      long-term users of the LNG-IUS.

PMID- 16436497
TI  - Metalloproteinase inhibitor counters high-energy phosphate depletion and AMP
      deaminase activity enhancing ventricular diastolic compliance in subacute heart
      failure.
AB  - Cardiac matrix metalloproteinases (MMPs) stimulated by the sympathomimetic action
      of angiotensin II (AII) exacerbate chamber diastolic stiffening in models of
      subacute heart failure. Here we tested the hypothesis that MMP inhibition
      prevents such stiffening by favorably modulating high-energy phosphate (HEP)
      stores more than by effects on matrix remodeling. Dogs were administered AII i.v.
      for 1 week with tachypacing superimposed in the last two days (AII+P; n = 8). A
      second group (n = 9) underwent the same AII+P protocol but was preceded by oral
      treatment with an MMP inhibitor PD166793 [(S)-2-(4-bromo-biphenyl-4-sulfonylamino
      3-methyl butyric acid] 1 week before and during the AII+P period. Pressure-volume
      analysis was performed in conscious animals, and myocardial tissue was subjected
      to in vitro and in situ zymography, collagen content, and HEP analysis (high
      performance liquid chromatography). As reported previously, AII+P activated MMP9
      and MMP2 and specifically exacerbated diastolic stiffening (+130% in chamber
      stiffness). PD166793 cotreatment prevented these changes, although myocardial
      collagen content, subtype, and cross-linking were unaltered. AII+P also reduced
      ATP, free energy of ATP hydrolysis (DeltaG(ATP)), and phosphocreatine while
      increasing free [ADP], AMP catabolites (nucleoside-total purines), and lactate.
      PD166793 reversed most of these changes, in part due to its inhibition of AMP
      deaminase. MMP activation may influence cardiac diastolic function by mechanisms
      beyond modulation of extracellular matrix. Interaction between MMP activation and
      HEP metabolism may play an important role in mediating diastolic dysfunction.
      Furthermore, these data highlight a potential major role for increased AMP
      deaminase activity in diastolic dysfunction.

PMID- 16436498
TI  - Peripheral administration of a melanocortin 4-receptor inverse agonist prevents
      loss of lean body mass in tumor-bearing mice.
AB  - Cachexia affects many different chronically ill patient populations, including
      those with cancer. It results in loss of body weight, particularly of lean body
      mass (LBM), and is estimated to be responsible for over 20% of all cancer-related
      deaths. Currently, available drugs are ineffective, and new therapies are
      urgently needed. Melanocortin 4-receptor (MC4-R) blockade has been shown recently
      to be effective in preventing cancer cachexia in rodent models. In the present
      study, we have tested a MC4-R blocker, ML00253764 [2-{2-[2-(5-bromo-2
      methoxyphenyl)-ethyl]-3-fluorophenyl}-4,5-dihydro-1H-imidazolium hydrochloride]
      (Vos et al., 2004), in vitro and in vivo. In membranes of human embryonic kidney
      293 cells expressing human MC4-R, ML00253764 displaced [Nle(4), d-Phe(7)]-alpha
      melanocyte-stimulating hormone binding with an IC(50) of 0.32 microM. At
      concentrations above 1 microM, ML00253764 decreased cAMP accumulation (maximal
      reduction of -20%) indicative of inverse agonist activity. ML00253764 was
      administered twice daily (15 mg/kg s.c.) for 13 days to C57BL6 mice bearing s.c.
      Lewis lung carcinoma tumors. Food intake and body weight were measured, and body
      composition was assessed using magnetic resonance relaxometry. ML00253764
      stimulated light-phase food intake relative to vehicle-treated controls (p <
      0.05), although no effect was observed on 24-h food intake. During the 21 days of
      the experiment, the LBM of tumor vehicle-treated mice decreased (p < 0.05). In
      contrast, the tumor-bearing mice treated with ML00253764 maintained their LBM.
      These data support the view that MC4-R blockade may be a suitable approach for
      the treatment of cancer cachexia and that MC4-R inverse agonists may have
      potential as drug candidates.

PMID- 16436499
TI  - Comparison of the relative efficacy and potency of mu-opioid agonists to activate
      Galpha(i/o) proteins containing a pertussis toxin-insensitive mutation.
AB  - Pertussis toxin (PTX)-insensitive mutants of Galpha(i/o) proteins expressed in
      C6mu cells were used to examine the hypothesis that there are agonist-specific
      conformational states of the mu-opioid receptor with coupling preferences to
      different Galpha(i/o) subtypes, as measured by the degree of stimulation of
      [(35)S]guanosine 5'-O-(3-thio)triphosphate (GTPgammaS) binding. Binding of
      [(35)S]GTPgammaS to endogenous Galpha(i/o) proteins stimulated by the full mu
      opioid agonist [d-Ala(2),MePhe(4),Gly(5)-ol]enkephalin (DAMGO) was completely
      blocked by overnight treatment with 100 ng/ml PTX. Treatment for 4 h with lower
      concentrations led to a PTX-dependent reduction in the maximal effect of DAMGO
      but no alteration in the potency of DAMGO or morphine nor in the relative maximal
      effect (relative efficacy) of the partial agonists morphine and buprenorphine
      compared with the full agonist DAMGO. Using PTX-insensitive Galpha mutants in
      which the PTX-sensitive cysteine was replaced with isoleucine, the potency for a
      series of mu-opioid agonists was highest in cells expressing Galpha(i3) and
      Galpha(o) and lowest with Galpha(i1) and Galpha(i2), with no significant change
      in the order of potency, namely, etorphine >> endomorphin-1 = DAMGO = endomorphin
      2 = fentanyl = morphine >> meperidine. The order of agonist relative efficacy,
      etorphine = DAMGO = endomorphin-1 = endomorphin-2 = fentanyl > or = morphine > or
      = meperidine > buprenorphine > or = nalbuphine, was also the same across all of
      the PTX-insensitive Galpha(i/o) subtypes. Highest relative efficacy to stimulate
      [(35)S]GTPgammaS binding was seen with Galpha(i3). Consequently, reported
      observations of agonist-directed trafficking at mu-opioid receptors most likely
      involve non-PTX-sensitive Galpha protein mechanisms.

PMID- 16436500
TI  - The human organic cation transporter-1 gene is transactivated by hepatocyte
      nuclear factor-4alpha.
AB  - The organic cation transporter-1 (OCT1) mediates the hepatocellular uptake of
      cationic drugs and endobiotics from sinusoidal blood. The uptake rates of these
      compounds may depend on OCT1 expression level. Because little is known about the
      regulation of the human OCT1 (hOCT1) gene, we characterized the hOCT1 promoter
      with respect to DNA-response elements and their binding factors. By computer
      analysis, we identified two adjacent putative DNA-response elements for the liver
      enriched homodimeric nuclear receptor hepatocyte nuclear factor-4alpha (HNF
      4alpha) in the hOCT1 promoter. Each element is of the direct repeat (DR)-2
      format, containing directly repeated hexamers separated by two bases. In
      electrophoretic mobility shift assays, both elements directly interacted with HNF
      4alpha. A luciferase reporter construct containing the hOCT1 promoter was
      strongly activated by HNF-4alpha in transiently transfected Huh7 cells. Site
      directed mutagenesis of either DR-2 element alone or in combination severely
      decreased the HNF-4alpha-mediated activation of the hOCT1 promoter, indicating
      that both elements are functionally important. Because HNF-4alpha is a known
      target for bile acid-mediated suppression of transcription, we studied whether
      chenodeoxycholic acid (CDCA) suppresses hOCT1 gene expression by inhibiting HNF
      4alpha-mediated transactivation. Treatment of cells with CDCA could indeed
      suppress the activation of the endogenous hOCT1 gene by HNF-4alpha. In addition,
      bile acid-inducible transcriptional repressor, small heterodimer partner (SHP),
      inhibited activation of the reporter-linked hOCT1 promoter and of the endogenous
      hOCT1 gene by HNF-4alpha. In conclusion, the hOCT1 gene, encoding an important
      drug transporter in the human liver, is activated by HNF-4alpha and suppressed by
      bile acids via SHP.

PMID- 16436501
TI  - Pharmacological characterization and feeding-suppressive property of FMS586 [3
      (5,6,7,8-tetrahydro-9-isopropyl-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)
      urea hydrochloride], a novel, selective, and orally active antagonist for
      neuropeptide Y Y5 receptor.
AB  - We evaluated the pharmacological profiles of FMS586 [3-(5,6,7,8-tetrahydro-9
      isopropyl-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)-urea hydrochloride], a
      novel tetrahydrocarbazole derivative as a neuropeptide Y (NPY) Y5 receptor
      antagonist. This compound showed a highly selective in vitro affinity for Y5
      (IC(50) = 4.3 +/- 0.4 nM) relative to other NPY receptor subtypes like Y1 or Y2.
      Its binding to Y5 was found to be fully antagonistic from cyclic AMP accumulation
      assays in human embryonic kidney 293 cells. Pharmacokinetic analysis revealed
      sufficient oral availability and brain permeability of this compound accompanied
      with clear dose relation. We attempted to assess the selectivity of FMS586 and,
      thereby, to infer the physiological role of Y5 in the following feeding
      experiments in normal rats. An intracerebroventricular injection of NPY and Y5
      selective agonist peptide induced acute and robust feeding responses in satiated
      rats, and prior administration of FMS586 at the doses from 25 to 100 mg/kg
      clearly inhibited these responses by approximately 55 and 90%, respectively. This
      compound also showed dose-dependent but transient suppression in natural feeding
      models of both overnight fasting-induced hyperphagia and spontaneous daily
      intake. FMS586 did not modulate food intake induced by the topical injection of
      norepinephrine, galanin, or gamma-aminobutyric acid receptor agonist muscimol to
      the paraventricular nucleus. In addition, we confirmed the Y5-specific activity
      profile of FMS586 by immunohistochemical analysis. Taken together, we propose not
      only that our compound potentially expresses specific blockade of central Y5
      signals but also that Y5 receptor would certainly contribute to physiological
      regulation of food intake in normal rats, as suggested from its origin.

PMID- 16436502
TI  - Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and
      smallpox viruses and protect mice against vaccinia virus.
AB  - Chimpanzee Fabs against the B5 envelope glycoprotein of vaccinia virus were
      isolated and converted into complete mAbs with human gamma 1 heavy chain constant
      regions. The two mAbs (8AH8AL and 8AH7AL) displayed high binding affinities to B5
      (Kd of 0.2 and 0.7 nM). The mAb 8AH8AL inhibited the spread of vaccinia virus as
      well as variola virus (the causative agent of smallpox) in vitro, protected mice
      from subsequent intranasal challenge with virulent vaccinia virus, protected mice
      when administered 2 days after challenge, and provided significantly greater
      protection than that afforded by a previously isolated rat anti-B5 mAb (19C2) or
      by vaccinia immune globulin. The mAb bound to a conformational epitope between
      amino acids 20 and 130 of B5. These chimpanzee/human anti-B5 mAbs may be useful
      in the prevention and treatment of vaccinia virus-induced complications of
      vaccination against smallpox and may also be effective in the immunoprophylaxis
      and immunotherapy of smallpox.

PMID- 16436503
TI  - Activity- and calcineurin-independent nuclear shuttling of NFATc1, but not
      NFATc3, in adult skeletal muscle fibers.
AB  - The transcription factor NFATc1 may be involved in slow skeletal muscle gene
      expression. NFATc1 translocates from cytoplasm to nuclei during slow fiber type
      electrical stimulation of skeletal muscle fibers because of activation of the
      Ca(2+)-dependent phosphatase calcineurin, resulting in nuclear factor of
      activated T-cells (NFAT) dephosphorylation and consequent exposure of its nuclear
      localization signal. Here, we find that unstimulated adult skeletal muscle fibers
      exhibit a previously unanticipated nucleocytoplasmic shuttling of NFATc1 without
      appreciable nuclear accumulation. In resting fibers, the nuclear export inhibitor
      leptomycin B caused nuclear accumulation of NFATc1 (but not of isoform NFATc3)
      and formation of NFATc1 intranuclear bodies independent of calcineurin. The rate
      of nuclear uptake of NFATc1 was 4.6 times lower in resting fibers exposed to
      leptomycin B than during electrical stimulation. Inhibitors of glycogen synthase
      kinase and protein kinase A or of casein kinase 1 slowed the decay of nuclear
      NFATc1 after electrical stimulation, but they did not cause NFATc1 nuclear uptake
      in unstimulated fibers. We propose that two nuclear translocation pathways, one
      pathway mediated by calcineurin activation and NFAT dephosphorylation and the
      other pathway independent of calcineurin and possibly independent of NFAT
      dephosphorylation, determine the distribution of NFATc1 between cytoplasm and
      nuclei in adult skeletal muscle.

PMID- 16436504
TI  - Uncoupling the central spindle-associated function of the chromosomal passenger
      complex from its role at centromeres.
AB  - Survivin is a component of the chromosomal passenger complex (CPC) that plays a
      role in maintenance of an active spindle checkpoint and in cytokinesis. To study
      whether these different functions can be attributed to distinct domains within
      the Survivin protein, we complemented Survivin-depleted cells with a variety of
      point- and deletion-mutants of Survivin. We show that an intact baculovirus IAP
      repeat (BIR) domain is required for proper spindle checkpoint functioning, but
      dispensable for cytokinesis. In line with this, mutants lacking an intact BIR
      domain localized normally to the central spindle, but their localization to inner
      centromeres was severely perturbed. Consequently, these mutants failed to recruit
      Aurora B, Borealin/Dasra B, and BubR1 to centromeres and kinetochores, but they
      had retained the ability to recruit Aurora B and Borealin/Dasra B to the midzone
      and midbody. Thus, the C terminus of Survivin is sufficient for central spindle
      localization and execution of cytokinesis, but the additional presence of a
      functional BIR domain is essential for centromere targeting and spindle
      checkpoint function. Importantly, our data show that the function of the CPC at
      the centromere can be separated from its function at the central spindle and that
      execution of cytokinesis does not require prior concentration of the CPC at
      centromeres.

PMID- 16436505
TI  - HIV-1 Tat regulates endothelial cell cycle progression via activation of the
      Ras/ERK MAPK signaling pathway.
AB  - Tat, the transactivator of HIV-1 gene expression, is released by acutely HIV-1
      infected T-cells and promotes adhesion, migration, and growth of inflammatory
      cytokine-activated endothelial and Kaposi's sarcoma cells. It has been previously
      demonstrated that these effects of Tat are due to its ability to bind through its
      arginine-glycine-aspartic (RGD) region to the alpha5beta1 and alphavbeta3
      integrins. However, the signaling pathways linking Tat to the regulation of
      cellular functions are incompletely understood. Here, we report that Tat ligation
      on human endothelial cells results in the activation of the small GTPases Ras and
      Rac and the mitogen-activated protein kinase ERK, specifically through its RGD
      region. In addition, we demonstrated that Tat activation of Ras, but not of Rac,
      induces ERK phosphorylation. We also found that the receptor proximal events
      accompanying Tat-induced Ras activation are mediated by tyrosine phosphorylation
      of Shc and recruitment of Grb2. Moreover, Tat enabled endothelial cells to
      progress through the G1 phase in response to bFGF, and the process is linked to
      ERK activation. Taken together, these data provide novel evidence about the
      ability of Tat to activate the Ras-ERK cascade which may be relevant for
      endothelial cell proliferation and for Kaposi's sarcoma progression.

PMID- 16436506
TI  - PARP1 Is a TRF2-associated poly(ADP-ribose)polymerase and protects eroded
      telomeres.
AB  - Poly(ADP-ribose)polymerase 1 (PARP1) is well characterized for its role in base
      excision repair (BER), where it is activated by and binds to DNA breaks and
      catalyzes the poly(ADP-ribosyl)ation of several substrates involved in DNA damage
      repair. Here we demonstrate that PARP1 associates with telomere repeat binding
      factor 2 (TRF2) and is capable of poly(ADP-ribosyl)ation of TRF2, which affects
      binding of TRF2 to telomeric DNA. Immunostaining of interphase cells or metaphase
      spreads shows that PARP1 is detected sporadically at normal telomeres, but it
      appears preferentially at eroded telomeres caused by telomerase deficiency or
      damaged telomeres induced by DNA-damaging reagents. Although PARP1 is dispensable
      in the capping of normal telomeres, Parp1 deficiency leads to an increase in
      chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA
      in primary murine cells after induction of DNA damage. Our results suggest that
      upon DNA damage, PARP1 is recruited to damaged telomeres, where it can help
      protect telomeres against chromosome end-to-end fusions and genomic instability.

PMID- 16436507
TI  - The Saccharomyces cerevisiae spindle pole body (SPB) component Nbp1p is required
      for SPB membrane insertion and interacts with the integral membrane proteins
      Ndc1p and Mps2p.
AB  - The spindle pole body (SPB) in Saccharomyces cerevisiae functions to nucleate and
      organize spindle microtubules, and it is embedded in the nuclear envelope
      throughout the yeast life cycle. However, the mechanism of membrane insertion of
      the SPB has not been elucidated. Ndc1p is an integral membrane protein that
      localizes to SPBs, and it is required for insertion of the SPB into the nuclear
      envelope during SPB duplication. To better understand the function of Ndc1p, we
      performed a dosage suppressor screen using the ndc1-39 temperature-sensitive
      allele. We identified an essential SPB component, Nbp1p. NBP1 shows genetic
      interactions with several SPB genes in addition to NDC1, and two-hybrid analysis
      revealed that Nbp1p binds to Ndc1p. Furthermore, Nbp1p is in the Mps2p-Bbp1p
      complex in the SPB. Immunoelectron microscopy confirmed that Nbp1p localizes to
      the SPB, suggesting a function at this location. Consistent with this hypothesis,
      nbp1-td (a degron allele) cells fail in SPB duplication upon depletion of Nbp1p.
      Importantly, these cells exhibit a "dead" SPB phenotype, similar to cells mutant
      in MPS2, NDC1, or BBP1. These results demonstrate that Nbp1p is a SPB component
      that acts in SPB duplication at the point of SPB insertion into the nuclear
      envelope.

PMID- 16436508
TI  - Zonula occludens-1 function in the assembly of tight junctions in Madin-Darby
      canine kidney epithelial cells.
AB  - Zonula occludens (ZO)-1 was the first tight junction protein to be cloned and has
      been implicated as an important scaffold protein. It contains multiple domains
      that bind a diverse set of junction proteins. However, the molecular functions of
      ZO-1 and related proteins such as ZO-2 and ZO-3 have remained unclear. We now
      show that gene silencing of ZO-1 causes a delay of approximately 3 h in tight
      junction formation in Madin-Darby canine kidney (MDCK) epithelial cells, but
      mature junctions seem functionally normal even in the continuing absence of ZO-1.
      Depletion of ZO-2, cingulin, or occludin, proteins that can interact with ZO-1,
      had no discernible effects on tight junctions. Rescue of junction assembly using
      murine ZO-1 mutants demonstrated that the ZO-1 C terminus is neither necessary
      nor sufficient for normal assembly. Moreover, mutation of the PDZ1 domain did not
      block rescue. However, point mutations in the Src homology 3 (SH3) domain almost
      completely prevented rescue. Surprisingly, the isolated SH3 domain of ZO-1 could
      also rescue junction assembly. These data reveal an unexpected function for the
      SH3 domain of ZO-1 in regulating tight junction assembly in epithelial cells and
      show that cingulin, occludin, or ZO-2 are not limiting for junction assembly in
      MDCK monolayers.

PMID- 16436509
TI  - Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and
      is involved in chronological aging.
AB  - Apoptosis-inducing factor (AIF) and AIF-homologous mitochondrion-associated
      inducer of death (AMID) are both mitochondrial flavoproteins that trigger caspase
      independent apoptosis. Phylogenetic analysis suggests that these two proteins
      evolutionarily diverge back from their common prokaryote ancestor. Compared with
      AIF, the proapoptotic nature of AMID and its mode of action are much less
      clarified. Here, we show that overexpression of yeast AMID homologue internal
      NADH dehydrogenase (NDI1), but not external NADH dehydrogenase (NDE1), can cause
      apoptosis-like cell death, and this effect can be repressed by increased
      respiration on glucose-limited media. This result indicates that the regulatory
      network of energy metabolism, in particular the cross-talk between mitochondria
      and the rest of the cell, is involved in Ndi1p-induced yeast cell apoptosis. The
      apoptotic effect of NDI1 overexpression is associated with increased production
      of reactive oxygen species (ROS) in mitochondria. In addition, NDI1
      overexpression in sod2 background causes cell lethality in both fermentable and
      semifermentable media. Interruption of certain components in the electron
      transport chain can suppress the growth inhibition from Ndi1p overexpression. We
      finally show that disruption of NDI1 or NDE1 decreases ROS production and
      elongates the chronological life span of yeast, accompanied by the loss of
      survival fitness. Implication of these findings for Ndi1p-induced apoptosis is
      discussed.

PMID- 16436511
TI  - Senescence of human fibroblasts after psoralen photoactivation is mediated by ATR
      kinase and persistent DNA damage foci at telomeres.
AB  - Cellular senescence is a phenotype that is likely linked with aging. Recent
      concepts view different forms of senescence as permanently maintained DNA damage
      responses partially characterized by the presence of senescence-associated DNA
      damage foci at dysfunctional telomeres. Irradiation of primary human dermal
      fibroblasts with the photosensitizer 8-methoxypsoralen and ultraviolet A
      radiation (PUVA) induces senescence. In the present study, we demonstrate that
      senescence after PUVA depends on DNA interstrand cross-link (ICL) formation that
      activates ATR kinase. ATR is necessary for the manifestation and maintenance of
      the senescent phenotype, because depletion of ATR expression before PUVA prevents
      induction of senescence, and reduction of ATR expression in PUVA-senesced
      fibroblasts releases cells from growth arrest. We find an ATR-dependent
      phosphorylation of the histone H2AX (gamma-H2AX). After PUVA, ATR and gamma-H2AX
      colocalize in multiple nuclear foci. After several days, only few predominantly
      telomere-localized foci persist and telomeric DNA can be coimmunoprecipitated
      with ATR from PUVA-senesced fibroblasts. We thus identify ATR as a novel mediator
      of telomere-dependent senescence in response to ICL induced by photoactivated
      psoralens.

PMID- 16436510
TI  - Kiss-and-coat and compartment mixing: coupling exocytosis to signal generation
      and local actin assembly.
AB  - Regulated exocytosis is thought to occur either by "full fusion," where the
      secretory vesicle fuses with the plasma membrane (PM) via a fusion pore that then
      dilates until the secretory vesicle collapses into the PM; or by "kiss-and-run,"
      where the fusion pore does not dilate and instead rapidly reseals such that the
      secretory vesicle is retrieved almost fully intact. Here, we describe growing
      evidence for a third form of exocytosis, dubbed "kiss-and-coat," which is
      characteristic of a broad variety of cell types that undergo regulated
      exocytosis. Kiss-and-coat exocytosis entails prolonged maintenance of a dilated
      fusion pore and assembly of actin filament (F-actin) coats around the exocytosing
      secretory vesicles followed by direct retrieval of some fraction of the emptied
      vesicle membrane. We propose that assembly of the actin coats results from the
      union of the secretory vesicle membrane and PM and that this compartment mixing
      represents a general mechanism for generating local signals via directed membrane
      fusion.

PMID- 16436513
TI  - Heteromerization of innexin gap junction proteins regulates epithelial tissue
      organization in Drosophila.
AB  - Gap junctions consist of clusters of intercellular channels, which enable direct
      cell-to-cell communication and adhesion in animals. Whereas deuterostomes,
      including all vertebrates, use members of the connexin and pannexin multiprotein
      families to assemble gap junction channels, protostomes such as Drosophila and
      Caenorhabditis elegans use members of the innexin protein family. The molecular
      composition of innexin-containing gap junctions and the functional significance
      of innexin oligomerization for development are largely unknown. Here, we report
      that heteromerization of Drosophila innexins 2 and 3 is crucial for epithelial
      organization and polarity of the embryonic epidermis. Both innexins colocalize in
      epithelial cell membranes. Innexin3 is mislocalized to the cytoplasm in innexin2
      mutants and is recruited into ectopic expression domains defined by innexin2
      misexpression. Conversely, RNA interference (RNAi) knockdown of innexin3 causes
      mislocalization of innexin2 and of DE-cadherin, causing cell polarity defects in
      the epidermis. Biochemical interaction studies, surface plasmon resonance
      analysis, transgenesis, and biochemical fractionation experiments demonstrate
      that both innexins interact via their C-terminal cytoplasmic domains during the
      assembly of heteromeric channels. Our data provide the first molecular and
      functional demonstration that innexin heteromerization occurs in vivo and reveal
      insight into a molecular mechanism by which innexins may oligomerize into
      heteromeric gap junction channels.

PMID- 16436512
TI  - Distinct roles for the essential MYST family HAT Esa1p in transcriptional
      silencing.
AB  - Among acetyltransferases, the MYST family enzyme Esa1p is distinguished for its
      essential function and contribution to transcriptional activation and DNA double
      stranded break repair. Here we report that Esa1p also plays a key role in
      silencing RNA polymerase II (Pol II)-transcribed genes at telomeres and within
      the ribosomal DNA (rDNA) of the nucleolus. These effects are mediated through
      Esa1p's HAT activity and correlate with changes within the nucleolus. Esa1p is
      enriched within the rDNA, as is the NAD-dependent protein deacetylase Sir2p, and
      the acetylation levels of key Esa1p histone targets are reduced in the rDNA in
      esa1 mutants. Although mutants of both ESA1 and SIR2 have enhanced rates of rDNA
      recombination, esa1 effects are more modest yet result in distinct structural
      changes of rDNA chromatin. Surprisingly, increased expression of ESA1 can bypass
      the requirement for Sir2p in rDNA silencing, suggesting that these two enzymes
      with seemingly opposing activities both contribute to achieve optimal nucleolar
      chromatin structure and function.

PMID- 16436514
TI  - Phosphorylation of Xenopus Rad1 and Hus1 defines a readout for ATR activation
      that is independent of Claspin and the Rad9 carboxy terminus.
AB  - The DNA damage checkpoint pathways sense and respond to DNA damage to ensure
      genomic stability. The ATR kinase is a central regulator of one such pathway and
      phosphorylates a number of proteins that have roles in cell cycle progression and
      DNA repair. Using the Xenopus egg extract system, we have investigated regulation
      of the Rad1/Hus1/Rad9 complex. We show here that phosphorylation of Rad1 and Hus1
      occurs in an ATR- and TopBP1-dependent manner on T5 of Rad1 and S219 and T223 of
      Hus1. Mutation of these sites has no effect on the phosphorylation of Chk1 by
      ATR. Interestingly, phosphorylation of Rad1 is independent of Claspin and the
      Rad9 carboxy terminus, both of which are required for Chk1 phosphorylation. These
      data suggest that an active ATR signaling complex exists in the absence of the
      carboxy terminus of Rad9 and that this carboxy-terminal domain may be a specific
      requirement for Chk1 phosphorylation and not necessary for all ATR-mediated
      signaling events. Thus, Rad1 phosphorylation provides an alternate and early
      readout for the study of ATR activation.

PMID- 16436517
TI  - Determination of dose-build-up thickness for absorbed dose measurement in high
      energy electron-photon radiation at electron storage rings.
AB  - Radiation field during accidental electron beam loss near electron storage rings
      comprises of high-energy electrons and bremsstrahlung photons. Due to high-energy
      nature of the radiation, the absorbed dose is expected to build up with depth of
      the body of an exposed worker and hence absorbed dose measurements in 30 cm
      water/tissue equivalent phantom is essential. Carrying out the measurements with
      in such phantoms is not practically feasible for routine applications and hence
      the use of an equivalent solid material around the dosemeters would be
      convenient. Monte Carlo calculations have been carried out in order to determine
      the dose-build-up thickness required in copper and lead, corresponding to the
      maximum absorbed within 30 cm depth of water in such radiation fields. Equivalent
      build-up thickness calculated for a case was verified by measurement using an ion
      chamber detector. The results are found to be in agreement within +/-20%.

PMID- 16436515
TI  - DNA damage signaling and p53-dependent senescence after prolonged beta-interferon
      stimulation.
AB  - Interferons are cytokines with potent antiviral and antiproliferative activities.
      We report that although a transient exposure to beta-interferon induces a
      reversible cell cycle arrest, a sustained treatment triggers a p53-dependent
      senescence program. Beta-interferon switched on p53 in two steps. First, it
      induced the acetylation of p53 at lysine 320 and its dephosphorylation at serine
      392 but not p53 activity. Later on, it triggered a DNA signaling pathway, the
      phosphorylation of p53 at serine 15 and its transcriptional activity. In
      agreement, beta-interferon-treated cells accumulated gamma-H2AX foci and
      phosphorylated forms of ATM and CHK2. The DNA damage signaling pathway was
      activated by an increase in reactive oxygen species (ROS) induced by interferon
      and was inhibited by the antioxidant N-acetyl cysteine. More important, RNA
      interference against ATM inhibited p53 phosphorylation at serine 15, p53 activity
      and senescence in response to beta-interferon. Beta-interferon-induced senescence
      was more efficient in cells expressing either, p53, or constitutive allele of
      ERK2 or RasV12. Hence, beta-interferon-induced senescence targets preferentially
      cells with premalignant changes.

PMID- 16436516
TI  - Heterodimeric capping protein from Arabidopsis is regulated by phosphatidic acid.
AB  - The cytoskeleton is a key regulator of morphogenesis, sexual reproduction, and
      cellular responses to extracellular stimuli. Changes in the cellular architecture
      are often assumed to require actin-binding proteins as stimulus-response
      modulators, because many of these proteins are regulated directly by binding to
      intracellular second messengers or signaling phospholipids. Phosphatidic acid
      (PA) is gaining widespread acceptance as a major, abundant phospholipid in plants
      that is required for pollen tube tip growth and mediates responses to osmotic
      stress, wounding, and phytohormones; however, the number of identified effectors
      of PA is rather limited. Here we demonstrate that exogenous PA application leads
      to significant increases in filamentous actin levels in Arabidopsis suspension
      cells and poppy pollen grains. To investigate further these lipid-induced changes
      in polymer levels, we analyzed the properties of a key regulator of actin
      filament polymerization, the heterodimeric capping protein from Arabidopsis
      thaliana (AtCP). AtCP binds to PA with a K(d) value of 17 muM and stoichiometry
      of approximately 1:2. It also binds well to PtdIns(4,5)P(2), but not to several
      other phosphoinositide or acidic phospholipids. The interaction with PA inhibited
      the actin-binding activity of CP. In the presence of PA, CP is unable to block
      the barbed or rapidly growing and shrinking end of actin filaments. Precapped
      filament barbed ends can also be uncapped by addition of PA, allowing rapid
      filament assembly from an actin monomer pool that is buffered with profilin. The
      findings support a model in which the inhibition of CP activity in cells by
      elevated PA results in the stimulation of actin polymerization from a large pool
      of profilin-actin. Such regulation may be important for the response of plant
      cells to extracellular stimuli as well as for the normal process of pollen tube
      tip growth.

PMID- 16436518
TI  - Radon survey and exposure assessment in hospitals.
AB  - In this study radon (222Rn) in indoor air was surveyed in 201 rooms of 26 major
      hospitals in Slovenia and annual effective doses for 1025 persons working in the
      rooms surveyed were estimated. Instantaneous radon concentrations were measured
      with alpha scintillation cells, long-term average concentrations with etched
      track detectors and electret detectors, and radon, its progeny and equilibrium
      factor were continuously recorded with portable devices. Effective doses were
      estimated by using ICRP Publication 65 methodology. Only in seven rooms did the
      average radon concentration, obtained by 1 month exposing etched track detectors,
      exceed the national limit of 400 Bq m-3; and these places will be mitigated;
      elsewhere it was lower. Annual effective doses for 966 persons (94.2%) were
      estimated as <1 mSv, but for 10 persons they were between 2.1 and 7.3 mSv. The
      results warn that in an environment with generally low radon levels, 'hot' points
      may be found, and therefore radon surveys should be carefully designed and
      performed in order not to miss them.

PMID- 16436519
TI  - A Monte Carlo method to calculate the average solid angle subtended by a right
      cylinder to a source that is circular or rectangular, plane or thick, at any
      position and orientation.
AB  - This note describes the development of a short program for a personal computer to
      calculate the solid angle subtended by a right cylinder detector to a circular or
      rectangular, plane or thick source at any position and orientation to the
      cylinder. The program also calculates the number of hits on the cylinder side and
      on each end, and the average pathlength through the detector volume (assuming no
      scattering or absorption). The current performance of personal computers makes it
      realistic to model the order of 10(9) simulations of radiation emission and
      achieve accuracies of solid angle estimates typically better than 0.03%.

PMID- 16436520
TI  - Population dose in the vicinity of closed Hungarian uranium mine.
AB  - In order to determine the exposure to natural sources of radiation for people in
      the vicinity of remediated Hungarian uranium mine regional surveys were carried
      out. The surveys evaluated indoor radon concentrations and outdoor and indoor
      external gamma dose rates. Radon concentration has been measured with nuclear
      etched track detectors for 4 months in 129 houses in Kovagoszolos and in 23
      houses in Cserkut. In some houses measurements have been carried out for a year
      and the measurement results of the 4 months were corrected according to these.
      The corrected radon concentrations altered between 15 and 2314 Bq m(-3). An
      average of 257 Bq m(-3) in Kovagoszolos and 125 Bq m(-3) in Cserkut was measured.
      The average was 434 Bq m(-3) for the 48 houses within 100 m of the passage of the
      former mine that is under the village of Kovagoszolos. The higher values of
      Kovagoszolos are likely to be the result of the influence of mining. The
      terrestrial gamma-ray dose rate was measured outdoors and indoors at these
      houses. Values of 139 (62-233) nGy h(-1) and 133 (93-275) nGy h(-1) were measured
      in Kovagoszolos and Cserkut, respectively. The average annual effective doses for
      the two villages studied were 3 and 5 mSv y(-1), but the maximum value was 40 mSv
      y(-1).

PMID- 16436521
TI  - Comparison of observed skeleton retention of strontium in average indian adult
      with the value predicted by the ICRP biokinetic model.
AB  - The daily dietary intake of strontium and its content in skeleton, for an Indian
      adult population group were estimated by experimentally measuring its
      concentration in total cooked diet and autopsy skeleton samples using
      radiochemical neutron activation analysis. The data on daily dietary intake of
      strontium were used to compute its contents in skeleton using ICRP Publication 67
      biokinetic model for strontium. The theoretically computed value of strontium
      (213.8 mg) compared favourably with the measured values (GM 181.2 mg) in an urban
      population group living in Mumbai representing an average Indian adult (Reference
      Indian Man).

PMID- 16436522
TI  - Using total beta-activity measurements in milk to derive thyroid doses from
      Chernobyl fallout.
AB  - Following the Chernobyl accident, more than 200 childhood thyroid cancer cases
      have been observed in Brest Oblast of Belarus in territories slightly
      contaminated with 137Cs, but with suspected relatively high 131I fallout. The
      most helpful measurements available that can be used to estimate thyroid doses
      for the population of Brest Oblast are the total beta-activity measurements in
      cow's milk performed using DP-100 device within a few weeks after the accident.
      The 131I concentrations in milk were derived from the total beta-activity
      measurements on the basis of (1) a radioecological model used to estimate the
      variation with time of the radionuclide composition in milk and (2) the
      determination of the calibration factors of the DP-100 device for the most
      important radionuclides present in milk. As a result, 131I concentrations in milk
      were reconstructed for territories with different levels of 137Cs deposition. A
      non-linear dependence of the 131I concentration in milk on the 137Cs deposition
      density was obtained; it was used to estimate the thyroid doses from the
      consumption of 131I-contaminated cow's milk by the population of Brest Oblast.
      The average individual thyroid doses have been estimated to be 0.15, 0.18, 0.12,
      0.06, 0.04 and 0.03 Gy for newborn, children aged 1, 5, 10 and 15 y and adults,
      respectively. The collective thyroid dose for the entire population of Brest
      Oblast is estimated to be 64,500 man Gy, the contribution from the adult
      population being about one half of the total. The methodology that is described
      could be applied in the framework of epidemiological studies of the relationship
      between radiation exposure to the thyroid gland and thyroid cancer in areas where
      numerous total beta-activity measurements in cow's milk were performed within a
      few weeks after the accident.

PMID- 16436523
TI  - Clinical diagnostic indicators of renal and bone damage in rats intramuscularly
      injected with depleted uranium.
AB  - The toxic effects and changes in biochemical markers related to kidney and bone
      in depleted uranium (DU)-injected rats were examined in order to clarify the
      relation between clinical biochemical markers and the degree of damage in these
      organs. Male Wistar rats received a single injection in the femoral muscles of
      0.2, 1.0 or 2.0 mg kg(-1) of DU which was dissolved in nitric acid solution
      adjusted to pH 3.2, for comparison with the group injected with nitric acid
      solution, and the control group. Urine and faeces were collected periodically
      over a 24 h period. Thereafter, the rats were killed at 28 d after DU injection.
      The body weights of the DU-injected groups decreased dose-dependently for the
      first 3-7 d, and then began to increase. The DU concentrations in the urine and
      faeces decreased rapidly within 3-7 d after DU injection. Urinary N-acetyl-beta-D
      glucosaminidase (NAG)/creatinine peaked at the third day after DU injection, with
      a high correlation to the injected DU doses. There were high correlations among
      the injected DU doses, DU concentrations in the kidney and urinary NAG/creatinine
      values that were obtained at 28 d, respectively. The blood urea nitrogen (BUN)
      and creatinine in the serum also showed a high correlation with the DU-injected
      doses. The results indicated that urinary NAG/creatinine, BUN and creatinine in
      serum were useful indicators to diagnose the renal damage by DU, as well as to
      estimate the DU intake and concentration in the kidney when the intake is >2 mg
      kg(-1) DU. The total bone mineral density of the proximal metaphysis of the tibia
      decreased in the 2 mg kg(-1) DU group. In addition, alterations of the trabecular
      bone structure by inhibiting bone formation and promoting bone resorption were
      observed by bone histomorphometery. The bone biochemical markers osteocalcin,
      tartrate-resistance acid phosphatase, pyridinoline and rat-parathyroid hormone
      increased in all the DU injected groups, indicating that these markers were
      useful as sensitive indicators for diagnosing bone damage, even if the DU dose
      injected is low.

PMID- 16436524
TI  - Integrin-linked kinase (ILK) is highly expressed in first trimester human
      chorionic villi and regulates migration of a human cytotrophoblast-derived cell
      line.
AB  - The placenta represents a critically important fetal-maternal interaction.
      Trophoblast migration and invasion into the uterine wall is a precisely
      controlled process and aberrations in these processes are implicated in diseases
      such as preeclampsia. Integrin-linked kinase (ILK) is a multifunctional,
      cytoplasmic, serine/threonine kinase that has been implicated in regulating
      processes such as cell proliferation, survival, migration, and invasion; yet the
      temporal and spatial pattern of expression of ILK in human chorionic villi and
      its role in early human placental development are completely unknown. We
      hypothesized that ILK would be expressed in trophoblast subtypes of human
      chorionic villi during early placental development and that it would regulate
      trophoblast migration. Immunoblot analysis revealed that ILK protein was highly
      detectable in placental tissue samples throughout gestation. In floating branches
      of chorionic villi, from 6 to 15 wk of gestation immunofluorescence analysis of
      ILK expression in placental tissue sections demonstrated that ILK was highly
      detectable in the cytoplasm and membranes of villous cytotrophoblast cells and in
      stromal mesenchyme, whereas it was barely detectable in the syncytiotrophoblast
      layer. In anchoring branches of villi, ILK was highly localized to plasma
      membranes of extravillous trophoblast cells. Transient expression of dominant
      negative E359K-ILK in the villous explant-derived trophoblast cell line HTR8
      SVneo dramatically reduced migration into wounds compared to cells expressing
      wild-type ILK or empty vector. Therefore, our work has demonstrated that ILK is
      highly expressed in trophoblast subtypes of human chorionic villi during the
      first trimester of pregnancy and is a likely mediator of trophoblast migration
      during this period of development.

PMID- 16436525
TI  - Global protein expression profiling underlines reciprocal regulation of caveolin
      1 and endothelial nitric oxide synthase expression in ovariectomized sheep
      uterine artery by estrogen/progesterone replacement therapy.
AB  - Ovariectomized (OVX) ewes were assigned to receive vehicle, progesterone (P4, 0.9
      g controlled internal drug release vaginal implants), estradiol-17beta (E2, 5
      microg/kg bolus + 6 microg kg(-1) day(-1)), or P4 + E2 for 10 days (n = 3/group).
      Uterine artery endothelial proteins were mechanically isolated on Day 10. The
      samples were used for protein expression profiling by the Ciphergen Proteinchip
      system and immunoblotting analysis of endothelial nitric oxide synthase (NOS3,
      also termed eNOS) and caveolin 1. Uterine artery rings were cut and analyzed by
      immunohistochemistry to localize NOS3 and caveolin 1 expression. With the use of
      the IMAC3 protein chip with loading as little as 2 microg protein/sample, many
      protein peaks could be detected. Compared to vehicle controls, a approximately
      133.1-kDa protein was identified to be upregulated by 2- to 4-fold in OVX ewes
      receiving E2, P4, and their combination, whereas a approximately 22.6-kDa protein
      was downregulated by 2- to 4-fold in OVX ewes receiving E2 and E2/P4, but not P4
      treatments. Western blot analysis revealed that E2, P4, and their combination all
      increased NOS3 protein, whereas E2 and its combination with P4, but not P4 alone,
      downregulated caveolin 1 expression. Immunohistochemical analysis revealed that
      NOS3 was mainly localized in the endothelium and upregulated by E2, whereas
      caveolin 1 was localized in both endothelium and smooth muscle and downregulated
      by E2. Thus, our data demonstrate that uterine artery endothelial NOS3 and
      caveolin 1 are regulated reciprocally by estrogen replacement therapy. In keeping
      with the facts that E2, but not P4, causes uterine vasodilatation and that E2 and
      P4 increase NOS3 expression, but only E2 decrease caveolin 1 expression, our
      current study suggests that both increased NOS3 expression and decreased caveolin
      1 expression are needed to facilitate estrogen-induced uterine vasodilatation.

PMID- 16436526
TI  - Epididymal SPAM1 is a marker for sperm maturation in the mouse.
AB  - Sperm adhesion molecule 1 (SPAM1), is a glycosyl phoshatidylinositol-linked sperm
      membrane protein that is dually expressed in testis and epididymis. Epididymal
      SPAM1 is secreted in all three regions of the epididymis in all mammalian species
      studied, including humans. It shares the same molecular mass and neutral
      hyaluronidase activity as the testicular and sperm isoforms that are responsible
      for the penetration of the cumulus during fertilization. Using wild-type (W/T)
      sperm and those from mice homozygous for either a null (Spam1-/-) or mutant Spam1
      allele, which results in decreased mRNA and protein, we demonstrate that sperm
      binding of epididymal SPAM1 occurs in vitro after exposure to W/T sperm-free
      epididymal luminal fluid (ELF). Binding or adsorption that occurred after
      incubation at room temperature or 32 degrees C was detected immunocytochemically
      and confirmed quantitatively using flow cytometry. The localization of SPAM1 on
      the plasma membrane of Spam1-null sperm mimicked that seen in the W/T. The
      remarkable increase in binding on W/T caudal sperm indicates that they are not
      fully saturated with SPAM1 during storage, and suggests that uptake of epididymal
      SPAM1 in vivo augments testicular SPAM1. Spam1-null sperm exposed to W/T ELF for
      45-60 min during in vitro capacitation to allow epididymal SPAM1 binding showed a
      highly significant (P < 0.001) increase in cumulus penetration after 6-7 h
      compared to those incubated in ELF from null males. Similarly, the number of
      cumulus-free oocytes was also highly significantly greater (P < 0.001) than that
      for sperm capacitated in W/T SPAM1-antibody-inhibited ELF. Because epididymal
      SPAM1 uptake significantly increases cumulus penetration, we conclude that it is
      a marker of sperm maturation.

PMID- 16436527
TI  - Glucosamine supplementation during in vitro maturation inhibits subsequent embryo
      development: possible role of the hexosamine pathway as a regulator of
      developmental competence.
AB  - Glucose concentration during cumulus-oocyte complex (COC) maturation influences
      several functions, including progression of oocyte meiosis, oocyte developmental
      competence, and cumulus mucification. Glucosamine (GlcN) is an alternative hexose
      substrate, specifically metabolized through the hexosamine biosynthesis pathway,
      which provides the intermediates for extracellular matrix formation during
      cumulus cell mucification. The aim of this study was to determine the influence
      of GlcN on meiotic progression and oocyte developmental competence following in
      vitro maturation (IVM). The presence of GlcN during bovine IVM did not affect the
      completion of nuclear maturation and early cleavage, but severely perturbed
      blastocyst development. This effect was subsequently shown to be dose-dependent
      and was also observed for porcine oocytes matured in vitro. Hexosamine
      biosynthesis upregulation using GlcN supplementation is well known to increase O
      linked glycosylation of many intracellular signaling molecules, the best
      characterized being the phosphoinositol-3-kinase (PI3K) signaling pathway. We
      observed extensive O-linked glycosylation in bovine cumulus cells, but not
      oocytes, following IVM in either the presence or the absence of GlcN. Inhibition
      of O-linked glycosylation significantly reversed the effect of GlcN-induced
      reduction in developmental competence, but inhibition of PI3K signaling had no
      effect. Our data are the first to link hexosamine biosynthesis, involved in
      cumulus cell mucification, to oocyte developmental competence during in vitro
      maturation.

PMID- 16436529
TI  - Injection of somatic cell cytoplasm into oocytes before intracytoplasmic sperm
      injection impairs full-term development and increases placental weight in mice.
AB  - This study investigated the effects on fertilized embryo development of somatic
      cytoplasm after its injection into intact mouse oocytes. Mature oocytes collected
      from female B6D2F1 mice were injected with cumulus cell cytoplasm of different
      volumes and from different mouse strains (B6D2F1, ICR, and C57BL/6), or with
      embryonic cytoplasm. After culture for 1 h, B6D2F1 sperm were injected into those
      oocytes by intracytoplasmic sperm injection (ICSI). The oocytes were examined for
      pre- and postimplantation developmental competence. Increases in the volume of
      the somatic cytoplasm from onefold to fourfold resulted in an impairment of
      blastocyst development and full-term development (28% and 7%, respectively, vs.
      96% and 63%, respectively, in the control group; P < 0.01). An increase in the
      volume of somatic cytoplasm reduced the expression of POU5F1 (more commonly known
      as OCT4) in expanded blastocysts. The frequency of embryos that developed to the
      blastocyst stage did not differ when B6D2F1 or ICR somatic cytoplasm was
      injected, but injection of C57BL/6 somatic cytoplasm induced a two-cell block in
      embryo development. Injection of the cytoplasm from fertilized embryos did not
      reduce the frequency of embryos attaining full-term development. Interestingly,
      somatic cytoplasm significantly increased the placental weight of ICSI embryos,
      even the injection of onefold cytoplasm (0.20 +/- 0.02 [n = 32] vs. 0.12 +/- 0.02
      in the control group [n = 87]; P < 0.01). These findings indicate that the
      injection of somatic cytoplasm into oocytes before ICSI causes a decrease in
      preimplantation development, clearly impairs full-term development, and causes
      placental overgrowth in fertilized embryos. To our knowledge, placental
      overgrowth phenotypes are only caused by interspecies hybridization and cloning,
      and in genetically modified mice. Here, we report for the first time that somatic
      cytoplasm causes abnormal placentas in fertilized embryos. This study suggests
      that somatic cell cytoplasmic material is one cause of the low rate of full-term
      development in cloned mammals.

PMID- 16436530
TI  - Gestation age-related increase in 50-kDa rat uterine calcium-independent
      phospholipase A2 expression influences uterine sensitivity to polychlorinated
      biphenyl stimulation.
AB  - Phospholipase A2 (PLA2) enzymes catalyze the rate-limiting step in eicosanoid
      production by liberating arachidonic acid from membrane phospholipids. There is
      limited information regarding the expression pattern and activity of uterine PLA2
      enzymes during pregnancy. Polychlorinated biphenyls (PCBs) are a group of
      persistent environmental toxicants previously associated with decreased gestation
      length that are capable of activating PLA2. The purpose of the present study was
      to determine whether uterine sensitivity to PCB stimulation is dependent on PLA2
      expression, comparing rat uterine PLA2 expression in Gestational Day (gd) 10
      versus gd20. Western blot analysis revealed a significant increase in the
      expression of calcium-dependent PLA2G2A and a 50-kDa protein immunoreactive to
      calcium-independent PLA2G6 antibody in gd20 compared to gd10 rat uterine tissue.
      The increased expression of the 50-kDa PLA2G6 was associated with a gestational
      age-related increase in endometrial calcium-independent PLA2 activity that was
      sensitive to inhibition by bromoenol lactone (P < 0.05). Longitudinal uterine
      strips isolated from gd10 or gd20 rat were suspended in muscle baths to evaluate
      uterine contractions following exposure to the ortho substituted congener PCB 50.
      Exposure to 50 and 100 microM PCB 50 significantly increased the frequency of
      gd20, but not gd10, uteri compared to solvent (dimethyl sulfoxide) controls (P <
      0.05). Pharmacologic inhibition of PLA2G6, but not PLA2G2A, attenuated PCB
      induced stimulation of gd20 uterine contractions (P < 0.05). These data suggest
      that PCB 50 stimulates uterine contractions by activating endometrial PLA2G6.
      Furthermore, gestation age-related sensitivity to PCB is associated with an
      increase in the expression of a previously unidentified 50-kDa PLA2G6 in rat
      uterus.

PMID- 16436528
TI  - Mutual regulation of follicle-stimulating hormone signaling and bone
      morphogenetic protein system in human granulosa cells.
AB  - Bone morphogenetic proteins (BMPs) play critical roles in folliculogenesis by
      modulating the actions of follicle-stimulating hormone (FSH) in the ovary.
      However, the effects of FSH on the BMP system remain unknown. Here, we have
      investigated the effects of FSH on BMP signaling using the human granulosa-like
      tumor cell line KGN. KGN cells express BMP type I and type II receptors and the
      BMP signaling molecules SMADs. FSH administration upregulated BMP type IA
      (BMPR1A) and IB (BMPR1B) receptors, activin type II receptor (ACVR2), and BMP
      type II receptor (BMPR2). FSH also augmented SMAD1 and SMAD5 expression, and
      conversely, FSH suppressed the expression of the inhibitory SMADs, SMAD6 and
      SMAD7. Bioassays revealed that FSH enhances BMP-induced SMAD1/5/8 phosphorylation
      and cellular DNA synthesis induced by BMP6 and BMP7. Since overexpression of
      BMPR1A and BMPR1B, but not SMADs, significantly enhanced the BMP responses, these
      type I receptors were revealed to be limiting factors for BMP signaling in KGN
      cells. BMPs significantly suppressed progesterone synthesis induced by forskolin
      and dibutyryl-cAMP (BtcAMP) but had no effect on estradiol induced by the same
      factors. KGN cAMP levels induced by forskolin were not altered by BMPs,
      suggesting that BMPs regulate steroidogenesis at a level downstream of cAMP
      synthesis in KGN cells. In this regard, BMPs specifically reduced the STAR
      transcription, whereas the levels of CYP11A, HSD3B2, and CYP19 stimulated by
      forskolin as well as BtcAMP were not altered. Collectively, the two major
      factors, FSH-cAMP pathway and BMP system, are reciprocally and functionally
      linked. Given that BMPs downregulate FSH receptors in KGN cells, this interaction
      may contribute to fine-tuning of the mutual sensitivity toward BMP ligands and
      FSH.

PMID- 16436531
TI  - Mechanism of action of L-arginine on the vitality of spermatozoa is primarily
      through increased biosynthesis of nitric oxide.
AB  - The ability of sperm to fertilize the egg is primarily dependent on sperm
      motility and membrane integrity. Nitric oxide (NO) plays a decisive role in
      regulating multiple functions within the male reproductive system. The aim of the
      present study is to determine the mechanism by which L-arginine confers a
      protective action on spermatozoa obtained from the goat epididymis. NO is
      synthesized from L-arginine by the enzyme nitric oxide-synthase (NOS) present in
      spermatozoa. A possible participation of NO and NOS in arginine action has been
      suggested.

PMID- 16436532
TI  - Expression of nerve growth factor and its receptors NTRK1 and TNFRSF1B is
      regulated by estrogen and progesterone in the uteri of golden hamsters.
AB  - Experiments were conducted using female golden hamsters to identify the presence
      of nerve growth factor (NGF) and its receptors NTRK1 and TNFRSF1B in the uteri of
      female animals and regulation on their expression by estrogen and progesterone.
      NGF and its receptor NTRK1 were immunolocalized to luminal epithelial cells,
      glandular cells, and stromal cells. TNFRSF1B was immunolocalized in luminal
      epithelial and glandular cells, with no staining found in stromal cells of the
      uterine horns of normal cyclic golden hamsters. Strong immunostaining of NGF and
      its receptors NTRK1 and TNFRSF1B was observed in uteri on the day of proestrus as
      compared to the other stages of the estrous cycle. Results of immunoblot analysis
      of NGF revealed that there was a positive correlation between uterine NGF
      expression and plasma concentrations of estradiol-17beta. To clarify the effects
      of estrogen and progesterone on NGF, NTRK1, and TNFRSF1B expression, adult female
      golden hamsters were ovariectomized and treated with estradiol-17beta and/or
      progesterone. Immunoblot analysis and immunohistochemistry indicated that
      estradiol-17beta stimulated expression of NGF and its two receptors in the
      uterus. Treatment with progesterone also increased NGF and NTRK1 expression in
      the uterus. However, no additive effect of these steroids on expression of NGF
      and its receptors was observed. Changes in uterine weights induced by estradiol
      17beta and/or progesterone showed the same profile with that of NGF, suggesting
      that a proliferative act of NGF may be involved in uterine growth. These results
      suggest that NGF may play important roles in action of steroids on uterine
      function.

PMID- 16436533
TI  - The effects of medialization and anteromedialization of the tibial tubercle on
      patellofemoral mechanics and kinematics.
AB  - BACKGROUND: Medialization and anteromedialization of the tibial tubercle are used
      to correct patellar subluxation in adults. PURPOSE: To compare the effects of the
      2 osteotomies on patellofemoral joint contact pressures and kinematics. STUDY
      DESIGN: Controlled laboratory study. METHODS: Tibial tubercle osteotomies were
      performed on 10 cadaveric human knees. The knees were tested between 0 degrees
      and 90 degrees of flexion while dynamic patellofemoral joint contact pressure and
      kinematic data were simultaneously obtained. Four conditions were tested: normal
      knee alignment, simulated increased Q angle, postmedialization of the tibial
      tubercle, and postanteromedialization of the tubercle. RESULTS: An increased Q
      angle laterally translated the patella, shifted force to the lateral facet, and
      increased patella contact pressures. Both medialization and anteromedialization
      partially corrected the abnormal contact pressures. Medialization partially
      corrected the shift of force to the lateral facet induced by an increased Q
      angle, whereas the anteromedialization could not. Both medialization and
      anteromedialization corrected the patella maltracking. CONCLUSION: Medialization
      and anteromedialization are equivalent in their ability to correct abnormal
      patellar mechanics and kinematics.

PMID- 16436534
TI  - Iliacus muscle rupture with associated femoral nerve palsy after abdominal
      extension exercises: a case report.

PMID- 16436535
TI  - Incidence of injuries in elite French youth soccer players: a 10-season study.
AB  - BACKGROUND: Research on age-related injury incidence in elite youth soccer is
      needed to identify high-risk groups. PURPOSE: To investigate the incidence of
      soccer-related injuries in elite French youth players based at the Clairefontaine
      Football Center. STUDY DESIGN: Cohort study (Prevalence); Level of evidence, 1.
      METHODS: Injuries sustained by players in the younger than 14-, 15-, and 16-year
      old age groups during 10 seasons were diagnosed and documented by a sports
      physician according to type, location, severity, the date the injury occurred,
      and playing position. RESULTS: Altogether, 1152 injuries were documented across
      all age groups with 69.1% and 30.9% sustained during training and matches,
      respectively. A total of 4.8 injuries per 1000 hours' exposure time were recorded
      and 11.2 and 3.9 injuries per 1000 hours for matches and training, respectively.
      There was no significant difference in injury frequency between age groups. The
      youngest group sustained more training injuries (P < .05) and osteochondroses (P
      < .05) and fewer match injuries than did the oldest group. Injury incidence
      varied throughout the season, peaking in September in all groups. The majority of
      injuries lasted less than 1 week (60.2%), contusions were the predominant injury
      type (30.6%, P < .05), and the upper leg was the site most often injured (24.5%,
      P < .05). CONCLUSION: Those players younger than 14 years incurred more injuries
      in training and sustained more growth-related overuse disorders. Older players
      were more often injured during matches. Injury incidence and the frequency of
      overuse disorders were highest early in the season.

PMID- 16436536
TI  - Anatomical double-bundle anterior cruciate ligament reconstruction after valgus
      high tibial osteotomy: a biomechanical study.
AB  - BACKGROUND: Although anatomical double-bundle anterior cruciate ligament
      reconstruction can successfully restore normal knee biomechanics for knees with
      typical varus-valgus alignment, the efficacy of the same reconstruction method
      for knees after a valgus high tibial osteotomy is unclear. HYPOTHESIS: Anatomical
      double-bundle anterior cruciate ligament reconstruction for valgus knees after a
      high tibial osteotomy cannot restore normal knee kinematics and can result in
      abnormally high in situ forces in the ligament graft. STUDY DESIGN: Controlled
      laboratory study. METHODS: Ten cadaveric knees were subjected to valgus high
      tibial osteotomy followed by an anatomical double-bundle anterior cruciate
      ligament reconstruction. The valgus knees were tested using a robotic/universal
      force-moment sensor system before and after the ligament reconstruction. The knee
      kinematics in response to anterior tibial load and combined rotatory loads, as
      well as the corresponding in situ forces of the anterior cruciate ligament
      bundles and grafts, were compared between the ligament-intact and ligament
      reconstructed valgus knees. RESULTS: After reconstruction, the anterior tibial
      translation and internal tibial rotation for the valgus knee decreased
      approximately 2 mm and 2 degrees , respectively, at low flexion angles compared
      with those of the anterior cruciate ligament-intact knee (P < .05). The in situ
      forces in the posterolateral graft became 56% to 200% higher than those in the
      posterolateral bundle of the intact anterior cruciate ligament (P < .05).
      CONCLUSION: Performing an anatomical double-bundle anterior cruciate ligament
      reconstruction on knees after valgus high tibial osteotomy may overconstrain the
      knee and result in high forces in the posterolateral graft, which could
      predispose it to failure. CLINICAL RELEVANCE: Modifications of anterior cruciate
      ligament reconstruction procedures to reduce posterolateral graft force may be
      needed for valgus knees after a high tibial osteotomy.

PMID- 16436537
TI  - Anterior shoulder stabilization in collision athletes: arthroscopic versus open
      Bankart repair.
AB  - BACKGROUND: Collision athletes are reported to be at high risk for redislocation
      after anterior stabilization of shoulder instability. Some authors have suggested
      that arthroscopic stabilization produces results similar to those of open
      stabilization. PURPOSE: To evaluate the results of anterior shoulder
      stabilization in collision athletes and to compare the clinical results between
      the arthroscopic and open methods. HYPOTHESIS: Open stabilization might produce
      better results than does arthroscopic stabilization in collision athletes. STUDY
      DESIGN: Cohort study; Level of evidence, 4. METHODS: Forty-eight shoulders of 46
      collision athletes were enrolled for this study. The mean age of the patients at
      the time of surgery was 20 years, and the mean follow-up period was 72 months
      (range, 30-136 months). Sixteen shoulders underwent arthroscopic stabilization;
      32 shoulders had open repairs. RESULTS: Visual analog scale, Rowe, and Constant
      scores improved after surgery, but no statistically significant difference was
      found between the arthroscopic and open repair groups. Thirty-seven athletes
      (83%) returned to near-preinjury sports activity levels (>/= 90% recovery) after
      operation. Two patients (4%) had subluxation and 6 (12.5%) had redislocation
      after surgery. The number of shoulders with postoperative subluxation or
      dislocation was 4 (25%) in the arthroscopic group and 4 (12.5%) in the open group
      (P = .041). Revision surgery was performed on 5 shoulders (10.4%). CONCLUSIONS:
      There were 8 (16.5%) instances of postoperative instability among the collision
      athletes studied. The arthroscopic group yielded a higher failure rate than did
      the open group. The authors believe open stabilization to be a more reliable
      method for anterior shoulder instability in collision athletes.

PMID- 16436538
TI  - The relationship between menstrual cycle phase and anterior cruciate ligament
      injury: a case-control study of recreational alpine skiers.
AB  - BACKGROUND: Female athletes suffer a greater incidence of anterior cruciate
      ligament tears compared with male athletes when participating in common sports;
      however, very little is known about the factors that explain this disparity.
      STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Female
      recreational alpine skiers with an anterior cruciate ligament rupture and age
      matched control skiers provided a serum sample and self-reported menstrual
      history data immediately after injury. Both serum concentrations of progesterone
      and menstrual history were then used to group subjects into either preovulatory
      or postovulatory phases of the menstrual cycle. RESULTS: Analysis of serum
      concentrations of progesterone revealed that alpine skiers in the preovulatory
      phase of the menstrual cycle were significantly more likely to tear their
      anterior cruciate ligaments than were skiers in the postovulatory phase (odds
      ratio, 3.22; 95% confidence interval, 1.09-9.52; P = .027). Analysis of menstrual
      history data found similar results, but the difference was not statistically
      significant (odds ratio, 2.38; 95% confidence interval, 0.86-6.54; P = .086).
      CONCLUSION: The likelihood of sustaining an anterior cruciate ligament injury
      does not remain constant during the menstrual cycle; instead, the risk of
      suffering an anterior cruciate ligament disruption is significantly greater
      during the preovulatory phase of the menstrual cycle compared with the
      postovulatory phase. CLINICAL RELEVANCE: Phase of menstrual cycle may be one of
      the risk factors that influence knee ligament injury among female alpine skiers.
      The findings from this study should be considered in subsequent studies designed
      to identify persons at risk for anterior cruciate ligament injury and to develop
      intervention strategies.

PMID- 16436539
TI  - Volume changes in the menisci and articular cartilage of runners: an in vivo
      investigation based on 3-D magnetic resonance imaging.
AB  - BACKGROUND: Articular cartilage contributes to transferring enormous loads as
      uniformly as possible from one skeletal segment to the next. Whether it manages
      this task when subjected to the high repetitive loading cycles occurring during
      long-distance running and can remain intact is still the topic of controversy.
      PURPOSE: To investigate the changes in cartilaginous volumes of the tibia,
      patella, and medial and lateral menisci after extreme dynamic loading as occurs
      in long-distance runners. STUDY DESIGN: Controlled laboratory study. METHODS:
      Forty-eight knees of male athletes were studied (38 +/- 14 years). The subjects
      ran around a predetermined and precisely measured course (5, 10, 20 km), the
      beginning and end of the run being in the magnetic resonance imaging
      investigation room. The scan protocol was 60-minute rest period, first
      measurement, run, 3-minute delay, and second measurement. RESULTS: Overall, there
      were significant reductions in volume (P < .05) for the patella, tibia, and
      menisci. There was evidence of significant change after a running distance of 5
      km. A further statistical reduction of the volume could only be demonstrated for
      the medial meniscus after 10 and 20 km. CONCLUSION: Tibial, patellar, and
      meniscal cartilaginous volumes show not only load-dependent volume changes but
      also an asymptotic curve. This is the first time that meniscal volume changes due
      to loading have been used as an indicator of the important mechanical
      contribution that the menisci make to sustaining the knee during repetitive
      loading. CLINICAL RELEVANCE: On the basis of the results of this study, the
      authors assume that the cartilage is able to adapt well to the loads caused by
      running.

PMID- 16436540
TI  - Autologous chondrocyte implantation postoperative care and rehabilitation:
      science and practice.
AB  - Autologous chondrocyte implantation is an advanced, cell-based orthobiological
      technology used for the treatment of chondral defects of the knee. It has been in
      clinical use since 1987 and has been performed on 12 000 patients
      internationally; but despite having been in clinical use for more than 15 years,
      the evidence base for rehabilitation after autologous chondrocyte implantation is
      notably deficient. The authors review current clinical practice and present an
      overview of the principles behind autologous chondrocyte implantation
      rehabilitation practices. They examine the main rehabilitation components and
      discuss their practical applications within the overall treatment program, with
      the aim of facilitating the formulation of appropriate, individualized patient
      rehabilitation protocols for autologous chondrocyte implantation.

PMID- 16436541
TI  - Antibiotic prescribing for acute and recurrent cystitis in primary care: a 4 year
      descriptive study.
AB  - OBJECTIVES: To explore the antibiotic prescribing pattern for cystitis and the
      patient-related variables associated with prescription during a 4 year period
      among Italian general practitioners (GPs). METHODS: We obtained information from
      the 'Health Search Database' (HSD), an Italian general practice research
      database. From a total sample of 457 672 eligible patients aged >16 years
      registered up to December 2002, we included those whose diagnoses could be
      classified as acute (uncomplicated and complicated) and recurrent cystitis.
      Patients' features and prevalence of antibiotic users were assessed. RESULTS: Of
      35 129 cases diagnosed during the period 1999-2002, 96.0% of them were acute
      cystitis (39.2% recorded as uncomplicated). The prevalence of cases with acute
      complicated and uncomplicated cystitis slightly increased during the 4 year
      period, whereas it remained stable for recurrent cystitis. Most of the cystitis
      cases reported no diagnostic tests. More than 70% of patients were prescribed
      with at least one antibiotic, with a 4-fold increased risk of antibiotic use for
      acute cystitis throughout the study period. The prevalence of antibiotic users
      reached 86.2% for both acute uncomplicated and complicated cystitis in 2002, and
      81.5% for recurrent cystitis. Fluoroquinolones represented the most common
      antibiotics being prescribed although they markedly decreased during these years.
      Fosfomycin trometamol use increased dramatically, becoming the first choice for
      any type of cystitis. CONCLUSIONS: Data indicate an evident rise in antibiotic
      use mostly related to fosfomycin trometamol. They also indicate that such a
      prescriptive trend finds confirmation from the available evidence for acute
      uncomplicated cystitis, although the management of recurrent cystitis could be
      further improved.

PMID- 16436542
TI  - Activity of human beta-defensins 2 and 3 against ESBL-producing Klebsiella
      strains.
AB  - OBJECTIVES: To test the bactericidal activity of human beta-defensins (hBDs) 2
      and 3 against extended-spectrum beta-lactamase (ESBL)-producing Klebsiella
      strains. METHODS: Thirty-six Klebsiella pneumoniae and seventeen Klebsiella
      oxytoca ESBL-producing isolates from nosocomial infections were tested. The
      bactericidal activity of recombinantly synthesized hBD-2 and -3 was tested and
      the results were given either as lethal doses killing > or = 90% of bacteria
      (LD90s) or as MBCs (> or = 99.9% killing). RESULTS: Except for one intermediately
      susceptible strain (MBC = 25 mg/L), all other ESBL-producing strains were highly
      susceptible to both defensins (LD90s and MBCs < or = 12.5 mg/L). CONCLUSIONS: The
      results underline the high efficacy of hBD-2 and -3 against ESBL-producing
      Klebsiella, making both defensins attractive candidates as antimicrobial agents
      to combat these increasingly troublesome bacteria.

PMID- 16436543
TI  - Reduction in fluoroquinolone susceptibility among non-typhoidal strains of
      Salmonella enterica isolated from Finnish patients.
AB  - OBJECTIVES: The proportion of Salmonella isolates with reduced susceptibility to
      fluoroquinolones has increased during recent years in many countries, especially
      in South-east Asia. The present study was performed to evaluate the incidence of
      and changes in quinolone resistance in Salmonella isolates of either foreign or
      domestic origin in Finland. METHODS: A total of 1004 Salmonella isolates
      collected from Finnish patients between 2000 and 2004 were analysed for
      ciprofloxacin susceptibility. Of these isolates, 504 were of domestic origin and
      500 were of foreign origin, collected from travellers to 43 different countries.
      The Salmonella collection consisted of 89 different serotypes. All isolates
      belonged to non-typhoidal Salmonella enterica. RESULTS: Of all isolates, 3 (0.3%)
      were ciprofloxacin-resistant (MIC > or = 4 mg/L) and 214 (21.3%) exhibited
      reduced susceptibility to ciprofloxacin (MIC > or = 0.125-2 mg/L). The annual
      proportion of reduced susceptibility varied between 3 and 15% among the domestic
      Salmonella isolates (P = 0.123). Between 2000 and 2004, the annual proportion of
      reduced susceptibility increased significantly (from 23 to 39%; P = 0.001) among
      all foreign isolates as well as among those from Spain alone (from 4 to 73%; P <
      0.001). Among the isolates from Thailand, reduced ciprofloxacin susceptibility
      remained at a constantly high level (52-66%) throughout the study. CONCLUSIONS:
      Our results show that reduced fluoroquinolone susceptibility in S. enterica is
      not restricted to South-east Asia alone but continues to grow rapidly in many
      parts of the world including countries of the European Union.

PMID- 16436544
TI  - Evidence behind the WHO guidelines: hospital care for children.

PMID- 16436545
TI  - Poor social and interpersonal functioning prior to diagnosis predicts poor
      outcome for people with first episode psychosis.

PMID- 16436546
TI  - Risperidone improves restricted, repetitive, and stereotyped behaviour in
      autistic children and adolescents.

PMID- 16436547
TI  - Atomoxetine improves teacher rated symptoms in children with ADHD more than
      placebo.

PMID- 16436548
TI  - Multisystemic therapy reduces long term rearrest compared with usual treatment.

PMID- 16436549
TI  - Intramuscular haloperidol and olanzapine begin to reduce psychosis within 24
      hours.

PMID- 16436550
TI  - Review: no evidence to support gradual over abrupt switching of antipsychotics.

PMID- 16436551
TI  - Individual dietary education reduces olanzapine associated weight gain.

PMID- 16436552
TI  - Cognitive behavioural therapy does not improve outcome in obese women with binge
      eating disorder receiving a comprehensive very low calorie diet programme.

PMID- 16436553
TI  - Cognitive behavioural therapy reduces nocturnal panic in people with panic
      disorder.

PMID- 16436554
TI  - Cognitive therapy is more cost effective than standard care alone for bipolar
      disorder.

PMID- 16436555
TI  - Divalproex and lithium are similarly cost effective for adults with bipolar
      disorder.

PMID- 16436556
TI  - Pharmacotherapy and cognitive behavioural therapy: similarly cost effective
      compared with community referral for disadvantaged women with major depression.

PMID- 16436557
TI  - A structured activity programme reduces depressive symptoms in moderately
      depressed older men with coronary heart disease, but not women.

PMID- 16436558
TI  - Training nursing home care staff to recognise psychopathology improves their
      ability to identify depressed residents.

PMID- 16436559
TI  - Review: cholinesterase inhibitors reduce burden and care time for informal carers
      of people with Alzheimer's disease.

PMID- 16436560
TI  - Neither vitamin E nor donepezil delays progression from amnestic mild cognitive
      impairment to Alzheimer's disease in the long term.

PMID- 16436561
TI  - Review: light therapy is an effective treatment for seasonal affective disorder.

PMID- 16436562
TI  - Supported employment interventions are effective for people with severe mental
      illness.

PMID- 16436563
TI  - Epilepsy or a family history of epilepsy increases the risk of schizophrenia or
      schizophrenia-like psychosis.

PMID- 16436565
TI  - Suicide ideation and attempts are more prevalent in people aged 25-44 years in
      Australia but become less prevalent in older people.

PMID- 16436564
TI  - History of psychiatric hospital admission increases the risk of suicide less in
      the very old than in middle aged people.

PMID- 16436566
TI  - Young people admitted with self-injury had more severe psychiatric disorders in
      2000 than in 1990.

PMID- 16436567
TI  - About 26% of people in the US have an anxiety, mood, impulse control, or
      substance disorder.

PMID- 16436568
TI  - About 30% of men with schizophrenia or schizoaffective disorders have obsessive
      compulsive symptoms.

PMID- 16436569
TI  - Ambulatory-based clinical education: Flexner revisited.

PMID- 16436570
TI  - Meeting the challenges facing clinical research: solutions proposed by leaders of
      medical specialty and clinical research societies.
AB  - The development of a robust national clinical research enterprise is needed to
      improve health care, but faces formidable challenges. To define the impediments
      and formulate solutions, the Institute of Medicine's Clinical Research Roundtable
      convened leaders from medical specialty and clinical research societies in 2003.
      Participants considered how to influence clinical research funding priorities,
      promote mechanisms to train physicians and other health care professionals to
      conduct clinical research, and how to encourage health care providers to follow
      evidence-based medical practice. Consensus emerged on multiple issues, including
      intersociety collaboration, the need for a core clinical research curriculum for
      training the new cadre of clinical researchers, joint advocacy for increased
      funding of clinical research and for the education of policymakers and the public
      on the benefits of clinical research. Specific recommendations were made on
      mechanisms for recruitment, training, and retention of clinical research trainees
      and mentors. Steps were outlined (1) to overcome career disincentives and develop
      appropriate reward systems for mentors and trainees, (2) to encourage use of web
      based and continuing-medical-education-based mechanisms to bring practitioners up
      to date on issues in and results of clinical research, and (3) to create
      incentives for individuals, clinics, and hospitals to practice evidence-based
      medicine (EBM). Collectively, the response and proposed strategies can serve as a
      roadmap to improve clinical research funding and training, evidence-based medical
      practice, and health care quality.

PMID- 16436571
TI  - Policies of academic medical centers for disclosing financial conflicts of
      interest to potential research participants.
AB  - PURPOSE: To document the current state of institutional review board (IRB) and
      conflict of interest committee policies regarding disclosures of financial
      conflicts of interest to potential research participants, and to use this
      information to identify and share models for effectively achieving disclosure.
      METHOD: The authors identified the 123 U.S. academic medical centers that have
      IRBs and sought their IRB and institutional policies regarding financial
      conflicts of interest. In February and March 2004, using manual and key word
      searches, each institution's Web site was searched to identify documents
      containing information regarding the disclosure of financial conflicts of
      interest. Letters were sent to 24 institutions that had either no information or
      incomplete information posted on their Web sites. To assess institutions'
      guidelines for disclosure, the authors extracted and content coded each
      institution's information on disclosure. RESULTS: Relevant information was
      obtained from 120 (98%) academic medical centers (AMCs), of which 57 (48%)
      mentioned disclosing financial conflicts to potential research participants. Of
      these 57, 33 (58%) included verbatim language that could be used in informed
      consent documents. AMCs' recommendations and requirements for disclosure included
      details of the financial arrangement, administrative management of conflicts of
      interest, and encouragement of dialogue between the investigator and the
      potential research participant. CONCLUSIONS: Considerable variability exists
      concerning the specific information that should be disclosed. Most of the AMCs'
      policies were consistent with the goal of protection from legal liability.
      Significant questions remain, however, concerning the goals of disclosure and the
      most effective methods for achieving those goals.

PMID- 16436572
TI  - Creating an infrastructure for training in the responsible conduct of research:
      the University of Pittsburgh's experience.
AB  - In response to public concerns about the consequences of research misconduct,
      academic institutions have become increasingly cognizant of the need to implement
      comprehensive, effective training in the responsible conduct of research (RCR)
      for faculty, staff, students, and external collaborators. The ability to meet
      this imperative is challenging as universities confront declining financial
      resources and increasing complexity of the research enterprise. The authors
      describe the University of Pittsburgh's design, implementation, and evaluation of
      a Web-based, institution-wide RCR training program called Research and Practice
      Fundamentals (RPF). This project, established in 2000, was embedded in the
      philosophy, organizational structure, and technology developed through the
      Integrated Advanced Information Management Systems grant from the National
      Library of Medicine. Utilizing a centralized, comprehensive approach, the RPF
      system provides an efficient mechanism for deploying content to a large, diverse
      cohort of learners and supports the needs of research administrators by providing
      access to information about who has successfully completed the training. During
      its first 3 years of operation, the RPF served over 17,000 users and issued more
      than 38,000 training certificates. The 18 modules that are currently available
      address issues required by regulatory mandates and other content areas important
      to the research community. RPF users report high levels of satisfaction with
      content and ease of using the system. Future efforts must explore methods to
      integrate non-RCR education and training into a centralized, cohesive structure.
      The University of Pittsburgh's experience with the RPF demonstrates the
      importance of developing an infrastructure for training that is comprehensive,
      scalable, reliable, centralized, affordable, and sustainable.

PMID- 16436573
TI  - Data withholding and the next generation of scientists: results of a national
      survey.
AB  - PURPOSE: To provide the first national data on the nature, extent, and
      consequences of withholding among life science trainees. METHOD: In 2003, the
      authors surveyed 1,077 second-year doctoral students and postdoctoral fellows in
      life sciences at 50 U.S. universities, with a comparison group of trainees in
      computer science and chemical engineering. The study variables examined trainees'
      exposure to and the consequences of data withholding. RESULTS: Two hundred forty
      six trainees (23.0%) reported that they had asked for and been denied access to
      information, data, materials, or programming associated with published research
      and 221 (20.6%) to unpublished research. Eighty-five trainees (7.9%) reported
      that they had denied another academic scientist's request(s) related to their own
      published research. Five hundred thirty-three trainees (50.8%) reported that
      withholding had had a negative effect on the progress of their research, 508
      (48.5%) on the rate of discovery in their lab/research group, 472 (45.0%) on the
      quality of their relationships with academic scientists, 346 (33.0%) on the
      quality of their education, and 299 (28.5%) on the level of communication in
      their lab/research group. Trainees denied access to research were significantly
      more likely to report that data withholding had had a negative effect on several
      aspects of the educational experience. CONCLUSIONS: Data withholding had
      demonstrated negative effects on trainees. The life sciences, more so than
      chemical engineering or computer science, will have to address this issue among
      its trainees. Failure to do so could result in delayed research, inefficient
      training, and a culture of withholding among future life scientists.

PMID- 16436575
TI  - A program to provide regulatory support for investigator-initiated clinical
      research.
AB  - Investigator-initiated clinical trials represent a small but extremely important
      portion of medical research. In the process of translating basic science
      discoveries to novel therapies, new drugs or devices may be developed and tested.
      In light of increased compliance scrutiny, the need to streamline research
      projects, and the growing complexity of the U.S. Food and Drug Administration's
      (FDA's) regulations, the research leadership at the University of Minnesota
      Academic Health Center (AHC) determined in 2002 that a service should be
      established to address these issues. The assumption was that providing a service
      to assist researchers with regulatory obligations would result in additional
      clinical research that might not have been pursued due to perceived regulatory
      hurdles. The authors present an overview of the FDA regulatory process as it
      applies to investigator-initiated research involving investigational new drugs
      and investigational medical devices. The rationale for creating a program
      designed specifically to assist faculty with investigational new drug (IND)
      applications and investigational device exemption (IDE) applications is
      discussed. The services provided by the IND/IDE Assistance Program (IAP) at the
      University of Minnesota Academic Health Center are described. The value of the
      IAP to the AHC is presented along with examples of successes attributable to the
      IAP and lessons learned so far. Since the establishment of the IAP several issues
      that might have placed the university at risk have been identified. These issues
      have been addressed to help improve the ease in which investigator-initiated
      research is conducted and compliance is maintained.

PMID- 16436574
TI  - Data withholding in genetics and the other life sciences: prevalences and
      predictors.
AB  - PURPOSE: To better understand the variety and prevalence of data withholding in
      genetics and the other life sciences and to explore factors associated with these
      behaviors. METHOD: In 2000, a sample of 2,893 geneticists and other life
      scientists (OLS) at the 100 most research-intensive universities in the United
      States were surveyed concerning data withholding and sharing. The instrument was
      developed and pretested in 1999. The two primary outcome measures were
      withholding in verbal exchanges with colleagues about unpublished research
      (verbal withholding) and withholding as part of the publishing process
      (publishing withholding). The independent variables related to the personal
      characteristics, research characteristics of faculty, and previous experience
      with data withholding. RESULTS: A total of 1,849 faculty responded (64%): 1,240
      geneticists and 600 OLS. Forty-four percent of geneticists and 32% of OLS
      reported participating in any one of 13 forms of data withholding in the three
      previous years. Publishing withholding (geneticists 35%, OLS 25%) was more
      frequent than verbal withholding (geneticists 23%, OLS 12%). In multivariate
      analyses, male gender, participation in relationships with industry, mentors'
      discouraging data sharing, receipt of formal instruction in data sharing, and
      negative past experience with sharing were significantly associated with either
      verbal or publishing withholding among either geneticists or OLS. CONCLUSIONS:
      Data withholding is common in biomedical science, takes multiple forms, is
      influenced by a variety of characteristics of investigators and their training,
      and varies by field of science. Encouraging openness during the formative
      experiences of young investigators may be critical to increased data sharing, but
      the effects of formal training do not appear straightforward.

PMID- 16436576
TI  - Guidelines for interactions between clinical faculty and the pharmaceutical
      industry: one medical school's approach.
AB  - A productive and ethical relationship between the pharmaceutical industry and
      physicians is critical to improving drug discovery and public health. In response
      to concerns about inappropriate financial relationships between the
      pharmaceutical industry and physicians, national organizations representing
      physicians or industry have made recommendations designed to reduce conflicts of
      interest, legal exposure, and dissemination of biased information. Despite these
      initiatives, the prescribing practices of physicians may be unduly influenced by
      the marketing efforts of industry and physicians may inadvertently distribute
      information that is biased in favor of a commercial entity. Moreover, physicians
      may be vulnerable to prosecution through federal anti-kickback and false claims
      statutes because of potentially inappropriate financial relationships with
      pharmaceutical companies. Since academic medical centers have a critical role in
      establishing professional standards, the faculty of Yale University School of
      Medicine developed guidelines for the relationships of faculty with the
      pharmaceutical industry, which were approved in May 2005. Input from clinical
      faculty and from representatives of the pharmaceutical industry was utilized in
      formulating the guidelines. In contrast to existing recommendations, the Yale
      guidelines, which are presented as an Appendix here, ban faculty from receiving
      any form of gift, meal, or free drug sample (for personal use) from industry, and
      set more stringent standards for the disclosure and resolution of financial
      conflict of interest in Yale's educational programs. The growing opportunities
      for drug discovery, the need to use medications in a more evidence-based manner,
      and preservation of the public trust require the highest professional standards
      of rigor and integrity. These guidelines are offered as part of the strategy to
      meet this compelling challenge.

PMID- 16436577
TI  - Medicine and the arts. In Flanders Fields by John McCrae. Commentary.

PMID- 16436579
TI  - Behavioral science education and the international medical graduate.
AB  - PURPOSE: International medical graduates (IMGs), many of whom are recent
      immigrants to the United States, are filling an increasing proportion of U.S.
      family medicine residency positions. Therefore, assumptions about the training
      experiences of first-year residents may no longer apply to a large percentage of
      incoming residents. The authors sought to improve the behavioral science
      education in their residency program by learning about IMGs' previous training
      and experience in behavioral science before coming to the United States. METHOD:
      Ten first-, second-, and third-year family medicine residents, representing
      medical school training from India, Macedonia, Bosnia-Herzegovina, The
      Philippines, Egypt, and Iraq, were individually interviewed using an inductive,
      qualitative approach. Transcripts were reviewed and double coded. Categories and
      story lines were identified, and member checking was employed. RESULTS: Segments
      were classified into seven categories: residents' behavioral medicine training
      prior to coming to the United States; reflections on the inclusion of mental
      health and psychosocial content in clinical family medicine; training in medical
      interviewing; reflections on the physician-patient relationship; perceptions of
      U.S. family life; recommendations for improving IMGs' understanding of
      psychosocial aspects of patient care; and specific challenges residents face as
      IMGs. CONCLUSIONS: The narrative data suggested several possible modifications to
      the family medicine curriculum, including expanding new resident orientation
      content about U.S. health care, introducing behavioral science content sooner,
      and having IMGs observe quality physician-patient interactions. Interview data
      also yielded concrete suggestions for improving residents' psychiatric interview
      knowledge and skills, such as instruction in specific wording of questions.

PMID- 16436580
TI  - International medical graduates and the diagnosis and treatment of late-life
      depression.
AB  - PURPOSE: International medical graduates (IMGs) constitute a significant number
      of physicians in the United States. Because of cultural differences in the
      manifestations and acceptance of mental disorders, depression may be less
      recognized in countries where IMGs train than in the United States. Differences
      in medical training may affect IMGs' recognition of depression. The authors
      hypothesized that the diagnosis and treatment of late-life depression would
      differ between United States medical graduates (USMGs) and IMGs. METHOD:
      Physicians, both USMGs and IMGs, at two different professional physician
      association meetings in 2002 were asked to view a multimedia computer program
      including a vignette of an elderly patient-actor with late-life depression. They
      completed a computerized survey, including their diagnosis and recommendations
      for management. Statistical analyses were performed to compare the two groups for
      physician characteristics and patient treatment recommendations. RESULTS: Study
      subjects were 178 primary care physicians and 321 psychiatrists. Three hundred
      fifty-three (71%) respondents were USMGs and 146 (29%) were IMGs. IMGs were
      significantly less likely than USMGs to make the correct diagnosis of depression
      (p < .004) or recommend treatment with a first-line antidepressant (p < .001).
      When specialty, other physician characteristics, and patient race and gender were
      controlled for, IMGs still differed significantly in their diagnoses (p = .006)
      and treatment (p = .006) of depression. CONCLUSION: The authors found significant
      differences between USMGs and IMGs for the diagnosis and treatment of late-life
      depression. This could be due to IMGs' lesser familiarity with depressive
      symptoms or different cultural conceptions of depression. These findings may
      point to the need for additional depression training initiatives for IMGs.

PMID- 16436581
TI  - Commentary: Coming to America: the integration of international medical graduates
      into the American medical culture.
AB  - This Commentary is a companion piece to two Research Reports appearing in this
      issue: "Behavioral Science Education and the International Medical Graduate," by
      Searight and Gafford, and "International Medical Graduates and the Diagnosis and
      Treatment of Late-Life Depression," by Kales et al. International medical
      graduates (IMGs) come to America from diverse cultures around the world to
      complete their graduate medical education (GME). These residents are and will
      continue to be a fundamental part of the American health care delivery system.
      IMGs' acculturation into the norms and standards of medicine as practiced in the
      U.S. is crucial to their education as well as to quality patient care. The time
      has come for GME to begin to systematically and effectively address the cultural
      challenges that IMGs face not only within the context of American medicine and
      GME, but in the larger context of American culture. Specific programs and
      strategies need to be developed and put in place early in the GME experience-or
      even before entry into GME-to assist IMGs in understanding the context for, and
      issues associated with, providing optimum health care in the United States. The
      author reflects on the findings of the two Research Reports, and calls for
      increased attention in the medical education community to acculturating and
      educating IMGs for optimal patient care.

PMID- 16436582
TI  - Always follow what you preach!

PMID- 16436583
TI  - The changing geography of Americans graduating from foreign medical schools.
AB  - PURPOSE: To study U.S.-born international medical graduates in order to analyze
      changes in their numbers and countries of training from the 1960s and before
      until the early 2000s. METHOD: This study was conducted from 2003-2004 at the
      Center for Health Workforce Studies, University of Washington. The analysis was
      based on data from March 2002 from the American Medical Association (AMA) for
      active physicians. AMA data were supplemented with data from several other
      sources. Descriptive statistics were produced on country of birth, country of
      medical school training, and year of training for all foreign-trained, patient
      care physicians whose birth country was known. RESULTS: At least 17,000 of the
      foreign-trained physicians practicing in the United States are known to have been
      born in the United States. American physicians have graduated from foreign
      medical schools in increasing numbers since the 1960s. The number of U.S.-born
      physicians who graduated from a foreign medical school peaked in the early 1980s,
      but the phenomenon endures today. However, the countries in which these
      physicians chose to attend medical schools have changed significantly from the
      1950s to the early 2000s. CONCLUSIONS: Over time, U.S.-born physicians have
      become much less likely to train in Europe and much more likely to train in
      certain Caribbean countries. U.S.-born physicians who graduate from medical
      schools abroad tend to train in just a handful of countries and attend a limited
      number of medical schools.

PMID- 16436584
TI  - Indian medical students' views on immigration for training and practice.
AB  - PURPOSE: To assess the attitudes of medical students in India about participating
      in graduate medical education in the United States and other countries and in
      subsequent clinical practice in those countries. METHOD: A total of 240 students
      who were attending their final year at two medical schools in Bangalore, India,
      were surveyed during 2004. Surveys were completed by 166 (69%) of the students.
      RESULTS: Among the responding students, 98 (59%) thought of leaving India for
      further training abroad. Of those who wished to leave, 41 (42%) preferred the
      United States, 42 (43%) preferred the United Kingdom, and 9 (9%) preferred
      Canada, Australia or New Zealand. Only two students preferred the Middle East.
      Most who favored training in the United States indicated that they intended to
      remain after training, whereas fewer than 20% of those who favored training in
      the United Kingdom had such intentions. While more than 60% perceived greater
      professional opportunities in the United States than in India, approximately 75%
      were concerned that the United States had become less welcoming after the
      terrorist attacks of 9/11, and similar numbers were concerned about the
      examination administered by the Educational Commission on Foreign Medical
      Graduates. Conversely, the majority of respondents felt that opportunities for
      physicians in India were improving. CONCLUSIONS: While optimism about future
      medical careers in India is increasing, the interest of Indian medical students
      in training and subsequently practicing in the United States remains high.

PMID- 16436585
TI  - Challenges and opportunities in the care of international patients: clinical and
      health services issues for academic medical centers.
AB  - International visitors who travel to the United States for the express purpose of
      receiving medical care constitute a small, but unique and important, subset of
      patients in this country. These visitors have traditionally sought care at what
      are widely regarded as the premier U.S. academic medical centers. Their care may
      prove challenging due to logistical, medical, language, and cross-cultural
      issues, and has the potential to distract from the educational and research
      missions of these medical centers. The author reflects on how one academic
      medical center, the Johns Hopkins Medical Institutions, has experienced and
      responded to these challenges. Specific issues include scheduling and evaluation
      challenges, language and cultural differences, and arranging continuity care. The
      author concludes that when an institution invests the resources necessary to
      address these issues, and enlists physicians stimulated by this challenging group
      of patients, the arrangement is mutually beneficial to the international patients
      and the institution. Scholarly evaluation of this phenomenon has been virtually
      nonexistent, due to both the unique niche occupied by these programs and
      institutional competition for this group of patients. However, collaborative
      evaluation of international patient programs will provide the opportunity to
      assess similarities, differences, and effectiveness, benefiting both those
      providing and those receiving care by improving the appropriateness and quality
      of care.

PMID- 16436586
TI  - A national collaboration to disseminate skills for outpatient teaching in
      internal medicine: program description and preliminary evaluation.
AB  - The shift of clinical care and teaching to outpatient settings has challenged
      ambulatory and community-based teachers. To address this challenge, U.S. internal
      medicine organizations devised "Faculty Development for General Internal
      Medicine: Generalist Faculty Teaching in Ambulatory Settings," a national program
      to train leaders to create local faculty development projects. In 1999, teams
      from all 386 internal medicine training institutions were invited to apply.
      Participation required an acceptable plan for a local project and inclusion of an
      institutional leader, residency or clerkship director, and a community-based
      faculty member on the project team. Team members attended one of three national
      training conferences held in 1999 and 2000 that included plenary sessions,
      workshops, and team meetings. Participants were invited to a wrap-up conference
      to present their accomplishments. One hundred ten teams from 57 university and 53
      non-university hospitals attended the training conferences; 412 (93%)
      participants returned conference evaluations. All sessions were rated highly.
      Participants preferred workshops and team meetings to plenary sessions. Two
      hundred thirty-five (57%) would have recommended the training conference to
      colleagues as an outstanding experience; 148 (36%) as a good experience; and 25
      (6%) as a satisfactory experience. Forty-nine teams (122 participants) returned
      for the wrap up conference where 35 teams presented their local faculty
      development projects. Cost per team trained was US$11,818. This program
      demonstrated a national desire for training in teaching skills, reached a broad
      audience of ambulatory-based clinical teachers, provided highly rated faculty
      development conferences in teaching skills, and facilitated development of a
      variety of local projects at modest expense. Partnerships were forged between
      academic leaders and community-based teachers.

PMID- 16436587
TI  - Bring your own G protein.
AB  - G protein-coupled receptor (GPCR)-Galpha fusion proteins were first characterized
      more than 10 years ago as a strategy for studying receptor-G protein signaling. A
      large number of studies have used this approach to characterize receptor coupling
      to members of the Gs, Gi, and Gq families of Galpha subunits, but this strategy
      has not been widely used to study Galpha12 and Galpha13. As described in the
      article by Zhang et al. in this issue of Molecular Pharmacology (p. 1433)
      characterization of the signaling properties of thromboxane A2 receptor (TPalpha)
      -Galpha12 and -Galpha13 fusion constructs demonstrates the applicability of this
      strategy to members of this unique family of Galpha subunits, and how this
      strategy can be used to resolve otherwise difficult problems of receptor
      pharmacology associated with these proteins. The general strategy of making
      receptor-Galpha fusion constructs has wide applicability to a number of research
      problems, but there are perhaps also "hidden messages" in how different receptor
      Galpha subunit fusion pairs behave.

PMID- 16436588
TI  - Potent inhibition of platelet-derived growth factor-induced responses in vascular
      smooth muscle cells by BMS-354825 (dasatinib).
AB  - Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are
      key events in the pathogenesis of restenosis that undermine the long-term benefit
      of widely performed balloon angioplasty and stenting procedures. Platelet-derived
      growth factor (PDGF) is a potent mitogen and motogen for VSMCs and is known to
      play a prominent role in the intimal accumulation of smooth muscle cells. In this
      study, we analyzed the effects of a novel protein tyrosine kinase inhibitor, BMS
      354825 (dasatinib), on PDGF-stimulated VSMCs. BMS-354825 is an orally
      bioavailable dual Src/Bcr-Abl tyrosine kinase inhibitor currently undergoing
      clinical trials in cancer patients. We found that BMS-354825 inhibited PDGF
      stimulated activation of PDGF receptor (PDGFR), STAT3, Akt, and Erk2 in rat A10
      VSMCs and in primary cultures of human aortic smooth muscle cells (AoSMCs) at low
      nanomolar concentrations. The 50% inhibition of the PDGFRbeta tyrosine kinase
      activity in vitro by BMS-354825 was observed at 4 nM. Direct comparison of BMS
      354825 and another PDGFR inhibitor, imatinib (Gleevec, STI571), in VSMCs
      indicated that BMS-354825 is 67-fold more potent than imatinib in inhibition of
      PDGFR activation. BMS-354825 also inhibited Src tyrosine kinase in A10 cells. At
      the cell level, PDGF stimulated migration and proliferation of A10 cells and
      human AoSMCs, both of which were inhibited by BMS-354825 in a concentration
      dependent manner in the low nanomolar range. These results suggest that BMS
      354825 is a potent inhibitor of PDGF-stimulated VSMC activities and a potential
      agent for the development of a new therapy for vascular obstructive diseases such
      as restenosis.

PMID- 16436589
TI  - Subunit dependencies of N-methyl-D-aspartate (NMDA) receptor-induced alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor internalization.
AB  - N-Methyl-D-aspartate (NMDA) receptor (NMDAR) activity regulates the net number of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR)
      at the cell surface by modulating the balance between AMPAR membrane insertion
      and endocytosis. In this study, we addressed the role of NMDAR subtypes and of
      NMDAR-mediated Ca2+ influx in the NMDAR-induced endocytosis of GluR2-containing
      AMPARs in primary murine hippocampal neurons. We found that NMDAR activation
      enhanced the endocytosis of AMPARs containing the GluR2 splice variants with
      short, but not long, cytoplasmic tails. NMDA-induced GluR2 endocytosis was
      completely inhibited by pharmacological block of NR2B-containing NMDARs. In turn,
      preferential block of NR2A-containing NMDARs did not affect NMDA-induced AMPAR
      endocytosis, indicating that AMPAR internalization is controlled by a restricted
      set of NMDARs. The NMDA-induced GluR2 internalization was also observed in the
      absence of extracellular Na+ ions, suggesting that membrane depolarization is not
      a prerequisite for this effect. Furthermore, the activation of Ca2+-impermeable
      NMDARs containing the mutant NR1(N598R) subunit failed to enhance AMPAR
      endocytosis, indicating a requirement of Ca2+ influx directly through the NMDAR
      channels. In summary, our findings suggest that the NMDAR-induced selective
      internalization of short C-terminal GluR2-containing AMPARs requires a Ca2+
      signal that originates from NMDAR channels and is processed in an NMDAR subtype
      restricted manner.

PMID- 16436590
TI  - Carry on eating: neural pathways mediating conditioned potentiation of feeding.

PMID- 16436591
TI  - Target-derived cues instruct synaptic differentiation.

PMID- 16436593
TI  - Involvement of the CA3-CA1 synapse in the acquisition of associative learning in
      behaving mice.
AB  - One of the brain sites more directly related with learning and memory processes
      is the hippocampus. We recorded, in conscious mice, the activity-dependent
      changes taking place at the hippocampal CA3-CA1 synapse during the acquisition,
      extinction, recall, and reconditioning of an associative task. Mice were
      classically conditioned to evoke eyelid responses using a trace [conditioned
      stimuli (CS), tone; unconditioned stimuli (US), shock] paradigm. A single
      electrical pulse presented to the Schaffer collateral-commissural pathway during
      the CS-US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1
      pyramidal cells. The slope of evoked fEPSPs increased across conditioning
      sessions and decreased during extinction, being linearly related to learning
      evolution. In contrast, fEPSPs were not modified when evoked in control mice in
      the absence of a conditioning protocol. Long-term potentiation (LTP) evoked by
      high-frequency stimulation of Schaffer collaterals prevented acquisition,
      extinction, recall, or reconditioning, depending on the moment when it was
      triggered. Learning and memory impairments evoked by LTP induction resulted
      probably from the functional saturation of the CA3-CA1 synapse, although an
      additional disturbance of the subsequent information transfer toward postsynaptic
      circuits cannot be discarded. CGP 39551 [(E)-(+/-)-2-amino-4-methyl-5-phosphono-3
      pentenoic acid ethyl ester] (an NMDA antagonist) prevented LTP induction in
      behaving mice, as well as the acquisition of an eyelid learned response, and the
      synaptic changes taking place at the CA3-CA1 synapse across conditioning. In
      conclusion, the responsivity of the CA3-CA1 synapse seems to be modulated during
      associative learning, and both processes are prevented by experimental LTP or
      NMDA-receptor inactivation. Our results provide evidence of a relationship
      between activity-dependent synaptic plasticity and associative learning in
      behaving mice.

PMID- 16436592
TI  - Splice variants of the NR1 subunit differentially induce NMDA receptor-dependent
      gene expression.
AB  - Subunits of the NMDA receptor (NMDAR) associate with many postsynaptic proteins
      that substantially broaden its signaling capacity. Although much work has been
      focused on the signaling of NR2 subunits, little is known about the role of the
      NR1 subunit. We set out to elucidate the role of the C terminus of the NR1
      subunit in NMDAR signaling. By introducing a C-terminal deletion mutant of the
      NR1 subunit into cultured neurons from NR1(-/-) mice, we found that the C
      terminus was essential for NMDAR inactivation, downstream signaling, and gene
      expression, but not for global increases in intracellular Ca2+. Therefore,
      whereas NMDARs can increase Ca2+ throughout the neuron, NMDAR-dependent
      signaling, both local and long range, requires coupling through the NR1 C
      terminus. Two major NR1 splice variants differ by the presence or absence of a C
      terminal domain, C1, which is determined by alternative splicing of exon 21.
      Analysis of these two variants showed that removal of this domain significantly
      reduced the efficacy of NMDAR-induced gene expression without affecting receptor
      inactivation. Thus, the NR1 C terminus couples to multiple downstream signaling
      pathways that can be modulated selectively by RNA splicing.

PMID- 16436594
TI  - Histaminergic neurons protect the developing hippocampus from kainic acid-induced
      neuronal damage in an organotypic coculture system.
AB  - The central histaminergic neuron system inhibits epileptic seizures, which is
      suggested to occur mainly through histamine 1 (H1) and histamine 3 (H3)
      receptors. However, the importance of histaminergic neurons in seizure-induced
      cell damage is poorly known. In this study, we used an organotypic coculture
      system and confocal microscopy to examine whether histaminergic neurons, which
      were verified by immunohistochemistry, have any protective effect on kainic acid
      (KA)-induced neuronal damage in the developing hippocampus. Fluoro-Jade B, a
      specific marker for degenerating neurons, indicated that, after the 12 h KA (5
      microM) treatment, neuronal damage was significantly attenuated in the
      hippocampus cultured together with the posterior hypothalamic slice containing
      histaminergic neurons [HI plus HY (POST)] when compared with the hippocampus
      cultured alone (HI) or with the anterior hypothalamus devoid of histaminergic
      neurons. Moreover, alpha-fluoromethylhistidine, an inhibitor of histamine
      synthesis, eliminated the neuroprotective effect in KA-treated HI plus HY (POST),
      and extracellularly applied histamine (1 nM to 100 microM) significantly
      attenuated neuronal damage only at 1 nM concentration in HI. After the 6 h KA
      treatment, spontaneous electrical activity registered in the CA1 subregion
      contained significantly less burst activity in HI plus HY (POST) than in HI.
      Finally, in KA-treated slices, the H3 receptor antagonist thioperamide enhanced
      the neuroprotective effect of histaminergic neurons, whereas the H1 receptor
      antagonists triprolidine and mepyramine dose-dependently decreased the
      neuroprotection in HI plus HY (POST). Our results suggest that histaminergic
      neurons protect the developing hippocampus from KA-induced neuronal damage, with
      regulation of neuronal survival being at least partly mediated through H1 and H3
      receptors.

PMID- 16436595
TI  - CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human
      immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier:
      a potential mechanism of HIV-CNS invasion and NeuroAIDS.
AB  - Encephalitis and dementia associated with acquired immunodeficiency syndrome
      (AIDS) are characterized by leukocyte infiltration into the CNS, microglia
      activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption,
      and eventual loss of neurons. Little is known about whether human
      immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to
      transmigrate in response to chemokines and to alter BBB integrity. We now
      demonstrate that HIV infection of human leukocytes results in their increased
      transmigration across our tissue culture model of the human BBB in response to
      the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced
      permeability, reduction of tight junction proteins, and expression of matrix
      metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did
      not transmigrate in the absence of CCL2, nor did this condition alter BBB
      integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa,
      CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on
      activation normal T-cell expressed and secreted) did not enhance HIV-infected
      leukocyte transmigration or BBB permeability. The increased capacity of HIV
      infected leukocytes to transmigrate in response to CCL2 correlated with their
      increased expression of CCR2, the chemokine receptor for CCL2. These data suggest
      that CCL2, but not other chemokines, plays a key role in infiltration of HIV
      infected leukocytes into the CNS and the subsequent pathology characteristic of
      NeuroAIDS.

PMID- 16436597
TI  - Allocentric spatial referencing of neuronal activity in macaque posterior
      cingulate cortex.
AB  - Neuronal activity in posterior cingulate cortex (CGp) is modulated by visual
      stimulation, saccades, and eye position, suggesting a role for this area in
      visuospatial transformations. The goal of this study was to determine whether
      neuronal responses in CGp are anchored to the eyes, head, or outside the body
      (allocentrically). To discriminate retinocentric from nonretinocentric spatial
      referencing, the activity of single CGp neurons was recorded while monkeys
      (Macaca mulatta) performed delayed-saccade trials initiated randomly from three
      different starting positions to a linear array of targets passing through the
      neuronal response field. For most neurons, tuning curves, segregated by fixation
      point, aligned more closely when plotted with respect to the display than when
      plotted with respect to the eye, suggesting a nonretinocentric frame of
      reference. A second experiment differentiated between spatial referencing in
      coordinates anchored to the head or body and allocentric spatial referencing.
      Monkeys shifted gaze from a central fixation point to the array of previously
      used targets both before and after whole-body rotation with respect to the
      display. For most neurons, tuning curves, segregated by fixation position,
      aligned more closely when plotted as a function of target position in the room
      than when plotted as a function of target position with respect to the monkey.
      These data indicate that a population of CGp neurons encodes visuospatial events
      in allocentric coordinates.

PMID- 16436596
TI  - Loss of p53 induces changes in the behavior of subventricular zone cells:
      implication for the genesis of glial tumors.
AB  - The role of multipotential progenitors and neural stem cells in the adult
      subventricular zone (SVZ) as cell-of-origin of glioblastoma has been suggested by
      studies on human tumors and transgenic mice. However, it is still unknown whether
      glial tumors are generated by all of the heterogeneous SVZ cell types or only by
      specific subpopulations of cells. It has been proposed that transformation could
      result from lack of apoptosis and increased self-renewal, but the definition of
      the properties leading to neoplastic transformation of SVZ cells are still
      elusive. This study addresses these questions in mice carrying the deletion of
      p53, a tumor-suppressor gene expressed in the SVZ. We show here that, although
      loss of p53 by itself is not sufficient for tumor formation, it provides a
      proliferative advantage to the slow- and fast-proliferating subventricular zone
      (SVZ) populations associated with their rapid differentiation. This results in
      areas of increased cell density that are distributed along the walls of the
      lateral ventricles and often associated with increased p53-independent apoptosis.
      Transformation occurs when loss of p53 is associated with a mutagenic stimulus
      and is characterized by dramatic changes in the properties of the quiescent adult
      SVZ cells, including enhanced self-renewal, recruitment to the fast-proliferating
      compartment, and impaired differentiation. Together, these findings provide a
      cellular mechanism for how the slow-proliferating SVZ cells can give rise to
      glial tumors in the adult brain.

PMID- 16436598
TI  - Long-term depression of NMDA receptor-mediated synaptic transmission is dependent
      on activation of metabotropic glutamate receptors and is altered to long-term
      potentiation by low intracellular calcium buffering.
AB  - Synaptic plasticity of NMDA receptor (NMDAR)-mediated transmission was
      investigated in the rat dentate gyrus in vitro. Isolated NMDAR EPSCs were
      recorded from granule cells of the dentate gyrus in response to stimulation of
      the medial perforant path. Long-term potentiation (LTP) or long-term depression
      (LTD) of NMDAR EPSCs was observed in response to brief high-frequency stimulation
      (HFS), with the direction and extent of plasticity dependent on the concentration
      and type (EGTA vs BAPTA) of the intracellular Ca2+ buffer. LTD was induced in
      higher concentrations of EGTA and BAPTA than LTP, and BAPTA was approximately 100
      fold more potent than EGTA. Although LTD was induced in a high concentration of
      EGTA (10 mM), a high concentration of BAPTA (10 mM) blocked both LTP and LTD. LTP
      of AMPA receptor (AMPAR)-EPSCs exhibited a lower dependency on Ca2+ buffering
      than LTP of NMDAR EPSCs, because LTP of AMPAR EPSCs was induced by HFS in high
      EGTA (10 mM). We also identified a role for metabotropic glutamate receptor 5
      (mGluR5) in NMDAR plasticity. HFS LTD was blocked by the group I/II mGluR
      antagonist LY341495 ((2S)-2-amino-2-[(1S, 2S)-2-carboxycycloprop-1-yl]-3(xanth-9
      yl)propanoic acid) and by the mGluR5-selective antagonist 2-methyl-6
      (phenylethynyl)pyridine hydrochloride (MPEP). Similarly, low-frequency
      stimulation-induced LTD of NMDAR EPSCs was also blocked by MPEP. These findings
      suggest that the direction of plasticity of NMDARs is determined by the
      intracellular free Ca2+ concentration and is dependent on activation of mGluR5.

PMID- 16436599
TI  - Goal representation in human anterior intraparietal sulcus.
AB  - When a child reaches toward a cookie, the watching parent knows immediately what
      the child wants. The neural basis of this ability to interpret other people's
      actions in terms of their goals has been the subject of much speculation.
      Research with infants has shown that 6 month olds respond when they see an adult
      reach to a novel goal but habituate when an adult reaches to the same goal
      repeatedly. We used a similar approach in an event-related functional magnetic
      resonance imaging experiment. Adult participants observed a series of movies
      depicting goal-directed actions, with the sequence controlled so that some goals
      were novel and others repeated relative to the previous movie. Repeated
      presentation of the same goal caused a suppression of the blood oxygen level
      dependent response in two regions of the left intraparietal sulcus. These regions
      were not sensitive to the trajectory taken by the actor's hand. This result
      demonstrates that the anterior intraparietal sulcus represents the goal of an
      observed action.

PMID- 16436600
TI  - Novel blockade of protein kinase A-mediated phosphorylation of AMPA receptors.
AB  - The phosphorylation state of the glutamate receptor subtype 1 (GluR1) subunit of
      the AMPA receptor (AMPAR) plays a critical role in synaptic expression of the
      receptor, channel properties, and synaptic plasticity. Several Gs-coupled
      receptors that couple to protein kinase A (PKA) readily recruit phosphorylation
      of GluR1 at S845. Conversely, activation of the ionotropic glutamate NMDA
      receptor (NMDAR) readily recruits dephosphorylation of the same GluR1 site
      through Ca2+-mediated recruitment of phosphatase activity. In a physiological
      setting, receptor activation often overlaps and crosstalk between coactivation of
      multiple signaling cascades can result in differential regulation of a given
      substrate. After investigating the effect of coactivation of the NMDAR and the Gs
      coupled beta-adrenergic receptor on GluR1 phosphorylation state, we have observed
      a novel signal that prevents PKA-mediated phosphorylation of GluR1 at serine site
      845. This blockade of GluR1 phosphorylation is dependent on cellular
      depolarization recruited by either NMDAR or AMPAR activation, independent of Ca2+
      and independent of calcineurin, protein phosphatase 1, and/or protein phosphatase
      2A activity. Thus, in addition to the typical kinase-phosphatase rivalry
      mediating protein phosphorylation state, we have identified a novel form of
      phospho-protein regulation that occurs at GluR1 and may also occur at several
      other PKA substrates.

PMID- 16436601
TI  - Arrestin translocation is induced at a critical threshold of visual signaling and
      is superstoichiometric to bleached rhodopsin.
AB  - Light induces massive translocation of major signaling proteins between the
      subcellular compartments of photoreceptors. Among them is visual arrestin
      responsible for quenching photoactivated rhodopsin, which moves into
      photoreceptor outer segments during illumination. Here, for the first time, we
      determined the light dependency of arrestin translocation, which revealed two key
      features of this phenomenon. First, arrestin translocation is triggered when the
      light intensity approaches a critical threshold corresponding to the upper limits
      of the normal range of rod responsiveness. Second, the amount of arrestin
      entering rod outer segments under these conditions is superstoichiometric to the
      amount of photoactivated rhodopsin, exceeding it by at least 30-fold. We further
      showed that it is not the absolute amount of excited rhodopsin but rather the
      extent of downstream cascade activity that triggers translocation. Finally, we
      demonstrated that the total amount of arrestin in the rod cell is nearly 10-fold
      higher than previously thought and therefore sufficient to inactivate the entire
      pool of rhodopsin at any level of illumination. Thus, arrestin movement to the
      outer segment leads to an increase in the free arrestin concentration and thereby
      may serve as a powerful mechanism of light adaptation.

PMID- 16436602
TI  - Dendrites contain a spacing pattern.
AB  - The distinctive branching patterns of dendritic arbors are essential for neuronal
      information processing. The final shape of an arbor is the result of intrinsic
      and extrinsic factors. However, the cellular mechanisms that underlie branch
      patterning are unknown. In many biological systems, locally acting factors are
      intrinsically organized into spacing patterns that guide patterned morphogenesis.
      Here, we show that neurons contain two types of periodic and regular elements
      (PADREN1s and PADREN2s) that are arranged into a spacing pattern. The wavelength
      of the pattern is approximately 20 microm. Dendritic branches occur
      preferentially within PADREN1s, and specific PADREN lengths correspond to
      specific arbor types. The lengths of the PADRENs also change over time and can be
      modified by activity. However, PADRENs are intrinsically organized, possibly by a
      reaction-diffusion process. PADRENs reveal a previously unrecognized level of
      neuronal organization that may provide insight into how the distinct branching
      patterns of the dendrites are intrinsically organized.

PMID- 16436604
TI  - Long-lasting memories of obstacles guide leg movements in the walking cat.
AB  - We examined the ways in which memories of previously seen obstacles can alter the
      stepping of walking cats. Cats were paused after the forelegs, but not the
      hindlegs, had stepped over an obstacle. Near the beginning of a variable delay
      period, the obstacle was lowered. On the subsequent step, the path of the
      hindlegs allowed us to make inferences about whether the memory of the obstacle
      was influencing leg movements. We present two main findings. First, the memory of
      the obstacle persisted for the duration that the animal straddled the original
      location of the obstacle. In one instance, this interval was 10 min. Second, this
      memory includes information regarding the size and position of the obstacle
      relative to the animal. This information is used to plan foot placement and to
      redirect the step in mid-swing to avoid the previous position of the obstacle.

PMID- 16436603
TI  - Transition from reversible to persistent binding of CaMKII to postsynaptic sites
      and NR2B.
AB  - Changes in protein-protein interactions and activity states have been proposed to
      underlie persistent synaptic remodeling that is induced by transient stimuli.
      Here, we show an unusual stimulus-dependent transition from a short-lived to long
      lasting binding between a synaptic receptor and its transducer. Both molecules,
      the NMDA receptor subunit NR2B and Ca2+/calmodulin (CaM)-dependent protein kinase
      II (CaMKII), are strongly implicated in mediating synaptic plasticity. We show
      that CaMKII reversibly translocates to synaptic sites in response to brief
      stimuli, but its resident time at the synapse increases after longer stimulation.
      Thus, CaMKII localization reflects temporal patterns of synaptic stimulation. We
      have identified two surface regions of CaMKII involved in short-lived and long
      term interactions with NR2B. Our results support an initial reversible and
      Ca2+/CaM-dependent binding at the substrate-binding site ("S-site"). On longer
      stimulation, a persistent interaction is formed at the T286-binding site ("T
      site"), thereby keeping the autoregulatory domain displaced and enabling Ca2+/CaM
      independent kinase activity. Such dual modes of interaction were observed in
      vitro and in HEK cells. In hippocampal neurons, short-term stimulation initiates
      a reversible translocation, but an active history of stimulation beyond some
      threshold produces a persistent synaptic localization of CaMKII. This activity
      dependent incorporation of CaMKII into postsynaptic sites may play a role in
      maturation and plasticity of synapses.

PMID- 16436605
TI  - Peripheral myelin protein 22 is in complex with alpha6beta4 integrin, and its
      absence alters the Schwann cell basal lamina.
AB  - Peripheral myelin protein 22 (PMP22) is a tetraspan membrane glycoprotein, the
      misexpression of which is associated with hereditary demyelinating neuropathies.
      Myelinating Schwann cells (SCs) produce the highest levels of PMP22, yet the
      function of the protein in peripheral nerve biology is unresolved. To investigate
      the potential roles of PMP22, we engineered a novel knock-out (-/-) mouse line by
      replacing the first two coding exons of pmp22 with the lacZ reporter. PMP22
      deficient mice show strong beta-galactosidase reactivity in peripheral nerves,
      cartilage, intestines, and lungs, whereas phenotypically they display the
      characteristics of tomaculous neuropathy. In the absence of PMP22, myelination of
      peripheral nerves is delayed, and numerous axon-SC profiles show loose basal
      lamina, suggesting altered interactions of the glial cells with the extracellular
      matrix. The levels of beta4 integrin, a molecule involved in the linkage between
      SCs and the basal lamina, are severely reduced in nerves of PMP22-deficient mice.
      During early stages of myelination, PMP22 and beta4 integrin are coexpressed at
      the cell surface and can be coimmunoprecipitated together with laminin and alpha6
      integrin. In agreement, in clone A colonic carcinoma cells, epitope-tagged PMP22
      forms a complex with beta4 integrin. Together, these data indicate that PMP22 is
      a binding partner in the integrin/laminin complex and is involved in mediating
      the interaction of SCs with the extracellular environment.

PMID- 16436606
TI  - Medullary raphe neurons facilitate brown adipose tissue activation.
AB  - Recent evidence suggests that neurons in the medullary raphe are critical to the
      activation of brown adipose tissue (BAT), the major source of nonshivering heat
      production in the rat. Yet it is unclear which medullary raphe cells participate
      in cold defense and how participating cells contribute to BAT activation.
      Therefore, we recorded extracellularly from raphe cells during three
      thermoregulatory challenges that evoked an increase in BAT temperature in
      anesthetized rats: central cold, ambient cold, or intracerebroventricular
      prostaglandin E2 (PGE2) injection. Physiologically identified serotonergic (p5HT)
      cell discharge increased in response to cold or PGE2 administration and was
      positively correlated with BAT temperature. However, none of the 147
      physiologically identified non-serotonergic (non-p5HT) cells recorded responded
      to thermoregulatory challenges that evoked an increase in BAT temperature. To
      test for modulation of BAT activation by non-p5HT cells that are either excited
      (ON cells) or inhibited (OFF cells) by noxious cutaneous stimulation, noxious
      stimuli were applied during evoked BAT temperature increases. Noxious stimulation
      suppressed BAT activation, suggesting that cells inhibited by noxious stimulation
      facilitate spinal circuits controlling BAT. To test whether medullary OFF cells
      modulate BAT activity, the mu-opiate receptor agonist (d-Ala2, N-Me-Phe4, Gly
      ol5)-enkephalin (DAMGO) was microinjected into the raphe magnus, a manipulation
      that selectively activates OFF cells. DAMGO microinjection blocked noxious
      stimulation-evoked suppression of PGE2-induced BAT temperature increases. Thus,
      both p5HT and non-p5HT OFF cells in the medullary raphe facilitate BAT activation
      in response to cold challenge or pyrogen.

PMID- 16436607
TI  - Simultaneous NMDA-dependent long-term potentiation of EPSCs and long-term
      depression of IPSCs in cultured rat hippocampal neurons.
AB  - A fundamental issue in understanding activity-dependent long-term plasticity of
      neuronal networks is the interplay between excitatory and inhibitory synaptic
      drives in the network. Using dual whole-cell recordings in cultured hippocampal
      neurons, we examined synaptic changes occurring as a result of a transient
      activation of NMDA receptors in the network. This enhanced transient activation
      led to a long-lasting increase in synchrony of spontaneous activity of neurons in
      the network. Simultaneous long-term potentiation of excitatory synaptic strength
      and a pronounced long-term depression of inhibitory synaptic currents (LTDi) were
      produced, which were independent of changes in postsynaptic potential and Ca2+
      concentrations. Surprisingly, miniature inhibitory synaptic currents were not
      changed by the conditioning, whereas both frequency and amplitudes of miniature
      EPSCs were enhanced. LTDi was mediated by activation of a presynaptic GABAB
      receptor, because it was blocked by saclofen and CGP55845 [(2S)-3-{[(15)-1-(3, 4
      dichlorophenyl)ethyl]amino-2-hydroxypropyl)(phenylmethyl)phosphinic acid]. The
      cAMP antagonist Rp-adenosine 3 ', 5 ' -cyclic monophosphothioate abolished all
      measured effects of NMDA-dependent conditioning, whereas a nitric oxide synthase
      inhibitor was ineffective. Finally, network-induced plasticity was not occluded
      by a previous spike-timing-induced plasticity, indicating that the two types of
      plasticity may not share the same mechanism. These results demonstrate that
      network plasticity involves opposite affects on inhibitory and excitatory
      neurotransmission.

PMID- 16436608
TI  - Prefrontal set activity predicts rule-specific neural processing during
      subsequent cognitive performance.
AB  - Prefrontal neurons have been shown to represent task rules. Here we show the
      mechanisms by which the rule-selective activity in the prefrontal cortex
      influences subsequent cognitive performance based on that rule. Using functional
      magnetic resonance imaging, we found that the frontopolar cortex interacted with
      posterior areas differently depending on whether subjects were going to perform a
      phonological or semantic task. Moreover, we found that the sustained "set"
      activity in this region predicted the activity that could be recorded in the
      posterior areas during the performance, as well as the speed of that performance.
      We argue that the prefrontal set activity does not reflect simple maintenance of
      the task rules but the process of implementing the rule for subsequent cognitive
      performance and that this is done through rule-selective interactions with areas
      involved in execution of the tasks.

PMID- 16436609
TI  - Barrel cortex microcircuits: thalamocortical feedforward inhibition in spiny
      stellate cells is mediated by a small number of fast-spiking interneurons.
AB  - Inhibitory and excitatory neurons located in rodent barrel cortex are known to
      form functional circuits mediating vibrissal sensation. Excitatory neurons
      located in a single barrel greatly outnumber interneurons, and form extensive
      reciprocal excitatory synaptic contacts. Inhibitory and excitatory networks must
      interact to shape information ascending to cortex. The details of these
      interactions, however, have not been completely explored. Using paired
      intracellular recordings, we studied the properties of synaptic connections
      between spiny neurons (i.e., spiny stellate and pyramidal cells) and
      interneurons, as well as integration of thalamocortical (TC) input, in layer IV
      barrels of rat thalamocortical slices. Results show the following: (1) the
      strength of unitary excitatory connections of spiny neurons is similar among
      different targets; (2) although inhibition from regular-spiking nonpyramidal
      interneurons to spiny neurons is comparable in strength to excitatory
      connections, inhibition mediated by fast-spiking (FS) interneurons is 10 times
      more powerful; (3) TC EPSPs elicit reliable and precisely timed action potentials
      in FS neurons; and (4) a small number of FS neurons mediate thalamocortical
      feedforward inhibition in each spiny neuron and can powerfully shunt TC-mediated
      excitation. The ready activation of FS cells by TC inputs, coupled with powerful
      feedforward inhibition from these neurons, would profoundly influence sensory
      processing and constrain runaway excitation in vivo.

PMID- 16436610
TI  - Involvement of the AMPA receptor GluR-C subunit in alcohol-seeking behavior and
      relapse.
AB  - Craving and relapse are core symptoms of drug addiction and alcoholism. It is
      suggested that, after chronic drug consumption, long-lasting neuroplastic changes
      within the glutamatergic system are important determinants of addictive behavior.
      Here, we show that the AMPA type glutamate receptor plays a crucial role in
      alcohol craving and relapse. We observed, in two animal models of alcohol craving
      and relapse, that the AMPA antagonist GYKI 52466 [1-(4-aminophenyl)-4-methyl-7, 8
      methylenedioxy-5H-2, 3-benzodiazepine] dose-dependently reduced cue-induced
      reinstatement of alcohol-seeking behavior and the alcohol deprivation effect. The
      involvement of the AMPA receptor in these phenomena was further studied using
      mice deficient for the GluR-C AMPA subunit [GluR-C knock-out (KO)]. GluR-C KOs
      displayed a blunted, cue-induced reinstatement response and alcohol deprivation
      effect, when compared with wild-type controls; however, no differences between
      genotypes could be observed regarding ethanol self-administration under operant
      or home cage drinking conditions. These results imply a role for GluR-C in
      alcohol relapse, although this phenotype could also be attributable to a
      reduction in the total number of AMPA receptors in specific brain areas. In
      conclusion, AMPA receptors seem to be involved in the neuroplastic changes
      underlying alcohol seeking behavior and relapse. Thus, AMPA receptors represent a
      novel therapeutic target in preventing relapse.

PMID- 16436611
TI  - Rab3 superprimes synaptic vesicles for release: implications for short-term
      synaptic plasticity.
AB  - Presynaptic vesicle trafficking and priming are important steps in regulating
      synaptic transmission and plasticity. The four closely related small GTP-binding
      proteins Rab3A, Rab3B, Rab3C, and Rab3D are believed to be important for these
      steps. In mice, the complete absence of all Rab3s leads to perinatal lethality
      accompanied by a 30% reduction of probability of Ca2+-triggered synaptic release.
      This study examines the role of Rab3 during Ca2+-triggered release in more detail
      and identifies its impact on short-term plasticity. Using patch-clamp
      electrophysiology of autaptic neuronal cultures from Rab3-deficient mouse
      hippocampus, we show that excitatory Rab3-deficient neurons display unique time-
      and frequency-dependent short-term plasticity characteristics in response to
      spike trains. Analysis of vesicle release and repriming kinetics as well as Ca2+
      sensitivity of release indicate that Rab3 acts on a subset of primed, fusion
      competent vesicles. They lower the amount of Ca2+ required for action potential
      triggered release, which leads to a boosting of release probability, but their
      action also introduces a significant delay in the supply of these modified
      vesicles. As a result, Rab3-induced modifications to primed vesicles causes a
      transient increase in the transduction efficacy of synaptic action potential
      trains and optimizes the encoding of synaptic information at an intermediate
      spike frequency range.

PMID- 16436612
TI  - Temporal dynamics and latency patterns of receptor neuron input to the olfactory
      bulb.
AB  - Odorants are first represented in the brain by distributed patterns of activity
      in the olfactory bulb (OB). Although neurons downstream of sensory inputs respond
      to odorants with temporally structured activity, sensory inputs to glomeruli are
      typically described as static maps. Here, we imaged the temporal dynamics of
      receptor neuron input to the OB with a calcium-sensitive dye in the olfactory
      receptor nerve terminals in anesthetized mice. We found that diverse, glomerulus-
      and odorant-dependent temporal dynamics are present even at this initial input
      stage. Instantaneous spatial patterns of receptor input to glomeruli changed both
      within and between respiration cycles. Glomerular odorant responses differed in
      amplitude, latency, rise time, and degree of modulation by sniffing in an odorant
      specific manner. Pattern dynamics within the first respiration cycle recurred in
      a similar manner during consecutive cycles. When sniff rate was increased
      artificially, pattern dynamics were preserved in the first sniff but were
      attenuated during subsequent sniffs. Temporal response properties were consistent
      across individuals on a coarse regional scale and on a fine scale of individual
      glomeruli. Latency and magnitude of glomerular inputs were only weakly correlated
      and might therefore convey independent odorant information. These data
      demonstrate that glomerular maps of primary sensory input to the OB are
      temporally dynamic. These dynamics may contribute to the representation of
      odorant information and affect information processing in the central olfactory
      system of rodents.

PMID- 16436613
TI  - Compartmentalized and signal-selective gap junctional coupling in the hearing
      cochlea.
AB  - Gap junctional intercellular communication (GJIC) plays a major role in cochlear
      function. Recent evidence suggests that connexin 26 (Cx26) and Cx30 are the major
      constituent proteins of cochlear gap junction channels, possibly in a unique
      heteromeric configuration. We investigated the functional and structural
      properties of native cochlear gap junctions in rats, from birth to the onset of
      hearing [postnatal day 12 (P12)]. Confocal immunofluorescence revealed increasing
      Cx26 and Cx30 expression from P0 to P12. Functional GJIC was assessed by
      coinjection of Lucifer yellow (LY) and Neurobiotin (NBN) during whole-cell
      recordings in cochlear slices. At P0, there was restricted dye transfer between
      supporting cells around outer hair cells. Transfer was more extensive between
      supporting cells around inner hair cells. At P8, there was extensive transfer of
      both dyes between all supporting cell types. By P12, LY no longer transferred
      between the supporting cells immediately adjacent to hair cells but still
      transferred between more peripheral cells. NBN transferred freely, but it did not
      transfer between inner and outer pillar cells. Freeze fracture further
      demonstrated decreasing GJIC between inner and outer pillar cells around the
      onset of hearing. These data are supportive of the appearance of signal-selective
      gap junctions around the onset of hearing, with specific properties required to
      support auditory function. Furthermore, they suggest that separate medial and
      lateral buffering compartments exist in the hearing cochlea, which are
      individually dedicated to the homeostasis of inner hair cells and outer hair
      cells.

PMID- 16436614
TI  - A critical role of erythropoietin receptor in neurogenesis and post-stroke
      recovery.
AB  - Erythropoietin (EPO) is the principal growth factor regulating the production of
      red blood cells. Recent studies demonstrated that exogenous EPO acts as a
      neuroprotectant and regulates neurogenesis. Using a genetic approach, we evaluate
      the roles of endogenous EPO and its classical receptor (EPOR) in mammalian
      neurogenesis. We demonstrate severe and identical embryonic neurogenesis defects
      in animals null for either the Epo or EpoR gene, suggesting that the classical
      EPOR is essential for EPO action during embryonic neurogenesis. Furthermore, by
      generating conditional EpoR knock-down animals, we demonstrate that brain
      specific deletion of EpoR leads to significantly reduced cell proliferation in
      the subventricular zone and impaired post-stroke neurogenesis. EpoR conditional
      knockdown leads to a specific deficit in post-stroke neurogenesis through
      impaired migration of neuroblasts to the peri-infarct cortex. Our results suggest
      that both EPO and EPOR are essential for early embryonic neural development and
      that the classical EPOR is important for adult neurogenesis and for migration of
      regenerating neurons during post-injury recovery.

PMID- 16436616
TI  - Spontaneous pain, both neuropathic and inflammatory, is related to frequency of
      spontaneous firing in intact C-fiber nociceptors.
AB  - Spontaneous pain, a poorly understood aspect of human neuropathic pain, is
      indicated in animals by spontaneous foot lifting (SFL). To determine whether SFL
      is caused by spontaneous firing in nociceptive neurons, we studied the following
      groups of rats: (1) untreated; (2) spinal nerve axotomy (SNA), L5 SNA 1 week
      earlier; (3) mSNA (modified SNA), SNA plus loose ligation of the adjacent L4
      spinal nerve with inflammation-inducing chromic gut; and (4) CFA (complete
      Freund's adjuvant), intradermal complete Freund's adjuvant-induced hindlimb
      inflammation 1 and 4 d earlier. In all groups, recordings of SFL and of
      spontaneous activity (SA) in ipsilateral dorsal root ganglion (DRG) neurons
      (intracellularly) were made. Evoked pain behaviors were measured in nerve injury
      (SNA/mSNA) groups. Percentages of nociceptive-type C-fiber neurons (C
      nociceptors) with SA increased in intact L4 but not axotomized L5 DRGs in SNA and
      mSNA (to 35%), and in L4/L5 DRGs 1-4 d after CFA (to 38-25%). SFL occurred in
      mSNA but not SNA rats. It was not correlated with mechanical allodynia, extent of
      L4 fiber damage [ATF3 (activation transcription factor 3) immunostaining], or
      percentage of L4 C-nociceptors with SA. However, L4 C-nociceptors with SA fired
      faster after mSNA (1.8 Hz) than SNA (0.02 Hz); estimated L4 total firing rates
      were approximately 5.0 and approximately 0.6 kHz, respectively. Similarly, after
      CFA, faster L4 C-nociceptor SA after 1 d was associated with SFL, whereas slower
      SA after 4 d was not. Thus, inflammation causes L4 C-nociceptor SA and SFL.
      Overall, SFL was related to SA rate in intact C-nociceptors. Both L5 degeneration
      and chromic gut cause inflammation. Therefore, both SA and SFL/spontaneous pain
      after nerve injury (mSNA) may result from cumulative neuroinflammation.

PMID- 16436615
TI  - A critical role for dorsal progenitors in cortical myelination.
AB  - Much controversy regarding the anatomical sources of oligodendrocytes in the
      spinal cord and hindbrain has been resolved. However, the relative contribution
      of dorsal and ventral progenitors to myelination of the cortex is still a subject
      of debate. To assess the contribution of dorsal progenitors to cortical
      myelination, we ablated the basic helix-loop-helix transcription factor Olig2 in
      the developing dorsal telencephalon. In Olig2-ablated cortices, myelination is
      arrested at the progenitor stage. Under these conditions, ventrally derived
      oligodendrocytes migrate dorsally into the Olig2-ablated territory but cannot
      fully compensate for myelination deficits observed at postnatal stages. Thus,
      spatially restricted ablation of Olig2 function unmasks a contribution of dorsal
      progenitors to cortical myelination that is much greater than hitherto
      appreciated.

PMID- 16436617
TI  - Rapid brain discrimination of sounds of objects.
AB  - Electrical neuroimaging in humans identified the speed and spatiotemporal brain
      mechanism whereby sounds of living and man-made objects are discriminated.
      Subjects performed an "oddball" target detection task, selectively responding to
      sounds of either living or man-made objects on alternating blocks, which were
      controlled for in their spectrogram and harmonics-to-noise ratios between
      categories. Analyses were conducted on 64-channel auditory evoked potentials
      (AEPs) from nontarget trials. Comparing responses to sounds of living versus man
      made objects, these analyses tested for modulations in local AEP waveforms,
      global response strength, and the topography of the electric field at the scalp.
      In addition, the local autoregressive average distributed linear inverse solution
      was applied to periods of observed modulations. Just 70 ms after stimulus onset,
      a common network of brain regions within the auditory "what" processing stream
      responded more strongly to sounds of man-made versus living objects, with
      differential activity within the right temporal and left inferior frontal
      cortices. Over the 155-257 ms period, the duration of activity of a brain
      network, including bilateral temporal and premotor cortices, differed between
      categories of sounds. Responses to sounds of living objects peaked approximately
      12 ms later and the activity of the brain network active over this period was
      prolonged relative to that in response to sounds of man-made objects. The
      earliest task-related effects were observed at approximately 100 ms poststimulus
      onset, placing an upper limit on the speed of cortical auditory object
      discrimination. These results provide critical temporal constraints on human
      auditory object recognition and semantic discrimination processes.

PMID- 16436618
TI  - Synaptic vesicle protein 2 enhances release probability at quiescent synapses.
AB  - We report a thorough analysis of neurotransmission in cultured hippocampal
      neurons lacking synaptic vesicle protein 2 (SV2), a membrane glycoprotein present
      in all vesicles that undergo regulated secretion. We found that SV2 selectively
      enhances low-frequency neurotransmission by priming morphologically docked
      vesicles. Loss of SV2 reduced initial release probability during a train of
      action potentials but had no effect on steady-state responses. The amount and
      decay rate of asynchronous release, two measures sensitive to presynaptic calcium
      concentrations, are not altered in SV2 knock-outs, suggesting that SV2 does not
      act by modulating presynaptic calcium. Normal neurotransmission could be
      temporarily recovered by delivering an exhaustive stimulus train. Our results
      indicate that SV2 primes vesicles in quiescent neurons and that SV2 function can
      be bypassed by an activity-dependent priming mechanism. We propose that SV2
      action modulates synaptic networks by ensuring that low-frequency
      neurotransmission is faithfully conveyed.

PMID- 16436619
TI  - A recurrent network mechanism of time integration in perceptual decisions.
AB  - Recent physiological studies using behaving monkeys revealed that, in a two
      alternative forced-choice visual motion discrimination task, reaction time was
      correlated with ramping of spike activity of lateral intraparietal cortical
      neurons. The ramping activity appears to reflect temporal accumulation, on a
      timescale of hundreds of milliseconds, of sensory evidence before a decision is
      reached. To elucidate the cellular and circuit basis of such integration times,
      we developed and investigated a simplified two-variable version of a
      biophysically realistic cortical network model of decision making. In this model,
      slow time integration can be achieved robustly if excitatory reverberation is
      primarily mediated by NMDA receptors; our model with only fast AMPA receptors at
      recurrent synapses produces decision times that are not comparable with
      experimental observations. Moreover, we found two distinct modes of network
      behavior, in which decision computation by winner-take-all competition is
      instantiated with or without attractor states for working memory. Decision
      process is closely linked to the local dynamics, in the "decision space" of the
      system, in the vicinity of an unstable saddle steady state that separates the
      basins of attraction for the two alternative choices. This picture provides a
      rigorous and quantitative explanation for the dependence of performance and
      response time on the degree of task difficulty, and the reason for which reaction
      times are longer in error trials than in correct trials as observed in the monkey
      experiment. Our reduced two-variable neural model offers a simple yet
      biophysically plausible framework for studying perceptual decision making in
      general.

PMID- 16436621
TI  - Not all lunatic fringe null female mice are infertile.

PMID- 16436622
TI  - URI-1 is required for DNA stability in C. elegans.
AB  - Unconventional prefoldin RPB5 interactor (URI), an evolutionary conserved member
      of the prefoldin family of molecular chaperones, plays a central role in the
      regulation of nutrient-sensitive, TOR (target-of-rapamycin)-dependent gene
      expression programs in yeast. Mammalian URI has been shown to associate with key
      components of the transcriptional machinery, including RPB5, a shared subunit of
      all three RNA polymerases, the ATPases TIP48 and TIP49, which are present in
      various chromatin remodeling complexes, and human PAF1 and parafibromin, which
      are components of a transcription elongation complex. Here, we provide the first
      functional characterization of a URI-1 homolog in a multicellular organism and
      show that the C. elegans gene uri-1 is essential for germ cell proliferation. URI
      1-deficient cells exhibit cell cycle arrest and display DNA breaks as evidenced
      by TUNEL staining and the appearance of HUS-1::GFP foci formation. In addition,
      uri-1(lf) mutants and uri-1(RNAi) worms show a p53-dependent increase in germline
      apoptosis. Our findings indicate that URI-1 has an important function in the
      mitotic and meiotic cell cycles. Furthermore, they imply that URI-1 participates
      in a pathway(s) that is associated with the suppression of endogenous genotoxic
      DNA damage and highlight a role for URI-1 in the control of genome integrity.

PMID- 16436623
TI  - Extracellular nucleotide signaling in adult neural stem cells: synergism with
      growth factor-mediated cellular proliferation.
AB  - We have previously shown that the extracellular nucleoside triphosphate
      hydrolyzing enzyme NTPDase2 is highly expressed in situ by stem/progenitor cells
      of the two neurogenic regions of the adult murine brain: the subventricular zone
      (type B cells) and the dentate gyrus of the hippocampus (residual radial glia).
      We explored the possibility that adult multipotent neural stem cells express
      nucleotide receptors and investigated their functional properties in vitro.
      Neurospheres cultured from the adult mouse SVZ in the presence of epidermal
      growth factor and fibroblast growth factor 2 expressed the ecto-nucleotidases
      NTPDase2 and the tissue non-specific isoform of alkaline phosphatase, hydrolyzing
      extracellular ATP to adenosine. ATP, ADP and, to a lesser extent, UTP evoked
      rapid Ca(2+) transients in neurospheres that were exclusively mediated by the
      metabotropic P2Y(1) and P2Y(2) nucleotide receptors. In addition, agonists of
      these receptors and low concentrations of adenosine augmented cell proliferation
      in the presence of growth factors. Neurosphere cell proliferation was attenuated
      after application of the P2Y(1)-receptor antagonist MRS2179 and in neurospheres
      from P2Y(1)-receptor knockout mice. In situ hybridization identified P2Y(1)
      receptor mRNA in clusters of SVZ cells. Our results infer nucleotide receptor
      mediated synergism that augments growth factor-mediated cell proliferation.
      Together with the in situ data, this supports the notion that extracellular
      nucleotides contribute to the control of adult neurogenesis.

PMID- 16436624
TI  - belladonna/(Ihx2) is required for neural patterning and midline axon guidance in
      the zebrafish forebrain.
AB  - Some of the earliest axon pathways to form in the vertebrate forebrain are
      established as commissural and retinal axons cross the midline of the
      diencephalon and telencephalon. To better understand axon guidance in the
      forebrain, we characterized the zebrafish belladonna (bel) mutation, which
      disrupts commissural and retinal axon guidance in the forebrain. Using a
      positional cloning strategy, we determined that the bel locus encodes zebrafish
      Lhx2, a lim-homeodomain transcription factor expressed in the brain, eye and fin
      buds. We show that bel(Ihx2) function is required for patterning in the ventral
      forebrain and eye, and that loss of bel function leads to alterations in
      regulatory gene expression, perturbations in axon guidance factors, and the
      absence of an optic chiasm and forebrain commissures. Our analysis reveals new
      roles for Ihx2 in midline axon guidance, forebrain patterning and eye
      morphogenesis.

PMID- 16436625
TI  - Smooth muscle of the dorsal aorta shares a common clonal origin with skeletal
      muscle of the myotome.
AB  - We show that cells of the dorsal aorta, an early blood vessel, and of the
      myotome, the first skeletal muscle to form within the somite, derive from a
      common progenitor in the mouse embryo. This conclusion is based on a
      retrospective clonal analysis, using a nlaacZ reporter targeted to the alpha
      cardiac actin gene. A rare intragenic recombination event results in a functional
      nlacZ sequence, giving rise to clones of beta-galactosidase-positive cells.
      Periendothelial and vascular smooth muscle cells of the dorsal aorta are the main
      cell types labelled, demonstrating that these are clonally related to the
      paraxial mesoderm-derived cells of skeletal muscle. Rare endothelial cells are
      also seen in some clones. In younger clones, arising from a recent recombination
      event, myotomal labelling is predominantly in the hypaxial somite, adjacent to
      labelled smooth muscle cells in the aorta. Analysis of Pax3(GFP/+) embryos shows
      that these cells are Pax3 negative but GFP positive, with fluorescent cells in
      the intervening region between the aorta and the somite. This is consistent with
      the direct migration of smooth muscle precursor cells that had expressed Pax3.
      These results are discussed in terms of the paraxial mesoderm contribution to the
      aorta and of the mesoangioblast stem cells that derive from it.

PMID- 16436626
TI  - Making progress in mental health policy in conservative times: one step at a
      time.
AB  - Progress in mental health services has been made incrementally in a sequence of
      policy steps. In recent years, in spite of political conservatism, progressive
      changes have advanced new principles of service delivery. Reports from the
      surgeon general and the President's New Freedom Commission on Mental Health
      advanced these principles, including recovery and evidence-based practices. Both
      of these high-level reports were influenced by the findings of the Schizophrenia
      Patient Outcomes Research Team (PORT). The Schizophrenia PORT established the
      effectiveness of mental health treatments and supports, which provided a
      scientific foundation for the optimistic focus on recovery and its expectation of
      improved outcomes for individuals with severe mental disorders. The PORT study
      also established the gap between treatment recommendations and actual services.
      Concern about this gap has motivated efforts to transform services by
      implementing evidence-based practices. Advances in broad mental health and social
      policy, coupled with continued advances in science, have the potential to improve
      the care of individuals who experience severe mental disorders, such as
      schizophrenia.

PMID- 16436627
TI  - Premorbid neurocognitive functioning in schizophrenia spectrum disorder.
AB  - A prospective study based on the U.S. National Collaborative Perinatal Project
      and using the Wechsler Intelligence Scale for Children (WISC) found lower test
      scores for the Coding subtest in preschizophrenic children than in their
      unaffected siblings. Using data on cognitive functioning in adolescence, the aim
      of the present prospective study was to examine whether low scores on Coding is
      associated with the risk of developing schizophrenia spectrum disorders. The 12
      subtests of the WISC were administered to 311 children and adolescents with a
      mean age of 15.1 years (range: 8 to 20 years), and the diagnostic assessment (DSM
      IIIR) was conducted by senior clinicians 25 years later. The group with
      schizophrenia spectrum disorder consisted of 84 individuals, and this group
      obtained significantly lower scores on Coding than nonschizophrenic controls.
      This difference could not be explained by differences in WISC IQ. Logistic
      regression analysis controlling for age at examination, gender, and social status
      yielded a significant, but relatively weak, association between low Coding test
      score and risk of schizophrenia spectrum disorder. For each unit increase in the
      Coding raw score, the adjusted odds ratio was 0.97 (95% CI 0.94-1.00) (p = .022),
      and the risk of schizophrenia spectrum disorder decreased by 3% (95% CI 6 to 0%).
      The Coding deficit on the WISC may indicate deficits in perceptual motor speed or
      in working memory processing speed in young individuals who later develop
      schizophrenia, schizotypal personality disorder, or other disorders within the
      schizophrenia spectrum.

PMID- 16436630
TI  - A single-tube nucleic acid extraction, amplification, and detection method using
      aluminum oxide.
AB  - A disposable 0.2-ml polymerase chain reaction (PCR) tube modified with an
      aluminum oxide membrane (AOM) has been developed for the extraction,
      amplification, and detection of nucleic acids. To assess the dynamic range of AOM
      tubes for real-time PCR, quantified herpes simplex virus (HSV) DNA was used to
      compare AOM tubes to standard PCR tubes. AOM PCR tubes used for amplification and
      detection of quantified HSV-1 displayed a crossing threshold (C(T)) shift 0.1
      cycles greater than PCR tube controls. Experiments with HSV-1-positive
      cerebrospinal fluid (CSF) examined the extraction, amplification, and detection
      properties of the AOM tubes compared to the Qiagen DNA blood mini kit. The AOM
      extraction, amplification, and detection of HSV-1 in CSF displayed differences of
      less than one C(T) when compared to Qiagen-extracted samples. Experiments testing
      the AOM method using clinical CSF samples displayed 100% concordance with
      reported results. AOM tubes have no adverse effects on amplification or
      fluorescence acquisition by real-time PCR and can be effectively used for the
      extraction, amplification, and detection of HSV from CSF. The AOM single tube
      method is a fast, reliable, and reproducible technique for the extraction,
      amplification, and detection of HSV in CSF.

PMID- 16436629
TI  - Nucleic acid amplification testing for Neisseria gonorrhoeae: an ongoing
      challenge.
AB  - Nucleic acid amplification tests (NAATs) for the detection of Neisseria
      gonorrhoeae became available in the early 1990s. Although offering several
      advantages over traditional detection methods, N. gonorrhoeae NAATs do have some
      limitations. These include cost, risk of carryover contamination, inhibition, and
      inability to provide antibiotic resistance data. In addition, there are sequence
      related limitations that are unique to N. gonorrhoeae NAATs. In particular, false
      positive results are a major consideration. These primarily stem from the
      frequent horizontal genetic exchange occurring within the Neisseria genus,
      leading to commensal Neisseria species acquiring N. gonorrhoeae genes.
      Furthermore, some N. gonorrhoeae subtypes may lack specific sequences targeted by
      a particular NAAT. Therefore, NAAT false-negative results because of sequence
      variation may occur in some gonococcal populations. Overall, the N. gonorrhoeae
      species continues to present a considerable challenge for molecular diagnostics.
      The need to evaluate N. gonorrhoeae NAATs before their use in any new patient
      population and to educate physicians on the limitations of these tests is
      emphasized in this review.

PMID- 16436632
TI  - Prognostic gene expression signatures can be measured in tissues collected in
      RNAlater preservative.
AB  - Gene expression signatures have the ability to serve in both prognostic and
      predictive capacities in patient management. The use of RNA as the starting
      material and the lability of this analyte, however, dictate that tissues must be
      snap-frozen or stored in a solution that can maintain the integrity of the RNA.
      We compared pairs of snap-frozen and RNAlater preservative-suspended tissue from
      30 such paired lymph node-negative breast tumors and 21 such paired Dukes' B
      colon tumors. We assessed the correlation of gene expression profiles and
      prediction of recurrence based on two prognostic algorithms. Tissues stored in
      RNAlater preservative generated expression profiles with excellent correlation
      (average Pearson correlation coefficients of 0.97 and 0.94 for the breast and
      colon tumor pairs, respectively) compared to those produced by tissues that were
      snap-frozen. The correlation in the prediction of recurrence was 97% and 95% for
      the breast and colon tumor pairs, respectively, between these two types of tissue
      handling protocols. This novel finding demonstrates that prognostic signatures
      can be obtained from RNAlater preservative-suspended tissues, an important step
      in bringing gene expression signatures to the clinic.

PMID- 16436631
TI  - Whole genome amplification of plasma-circulating DNA enables expanded screening
      for allelic imbalance in plasma.
AB  - Apoptotic and necrotic tumor cells release DNA into plasma, providing an
      accessible tumor biomarker. Tumor-released plasma-circulating DNA can be screened
      for tumor-specific genetic changes, including mutation, methylation, or allelic
      imbalance. However, technical problems relating to the quantity and quality of
      DNA collected from plasma hinder downstream genetic screening and reduce
      biomarker detection sensitivity. Here, we present a new methodology, blunt-end
      ligation-mediated whole genome amplification (BL-WGA), that efficiently amplifies
      small apoptotic fragments (<200 bp) as well as intermediate and large necrotic
      fragments (>5 kb) and enables reliable high-throughput analysis of plasma
      circulating DNA. In a single-tube reaction, purified double-stranded DNA was
      blunted with T4 DNA polymerase, self-ligated or cross-ligated with T4 DNA ligase
      and amplified via random primer-initiated multiple displacement amplification.
      Using plasma DNA from breast cancer patients and normal controls, we demonstrate
      that BL-WGA amplified the plasma-circulating genome by approximately 1000-fold.
      Of 25 informative polymorphic sites screened via polymerase chain reaction
      denaturating high-performance liquid chromatography, 24 (95%) were correctly
      determined by BL-WGA to be allelic retention or imbalance compared to 44% by
      multiple displacement amplification. By enabling target magnification and
      application of high-throughput genome analysis, BL-WGA improves sensitivity for
      detection of circulating tumor-specific biomarkers from bodily fluids or for
      recovery of nucleic acids from suboptimally stored specimens.

PMID- 16436633
TI  - Association of clinical status of follicular lymphoma patients after autologous
      stem cell transplant and quantitative assessment of lymphoma in blood and bone
      marrow as measured by SYBR Green I polymerase chain reaction.
AB  - Molecular remission in the autograft and bone marrow after transplant are
      predictive of durable clinical remission in relapsed follicular lymphoma. Thus, a
      simple reliable method to quantify minimal residual disease (MRD) would improve
      prognostication in these patients. Fluorescent hybridization probes have been
      used in real-time quantitative polymerase chain reaction (RQ-PCR) to monitor MRD
      with a reproducible sensitivity of 0.01%; however, these techniques are expensive
      and require additional experiments to examine clonality. We describe a SYBR Green
      I detection method that is more universal, checks clonal identity, yields the
      same sensitivity for monitoring MRD, and is more economically attractive. Using
      this method to follow 14 follicular lymphoma patients treated with autologous
      stem cell transplantation, molecular markers were successfully defined for 12
      patients. Median contamination of stem-cell grafts was 0.1% (range, 0 to 13%).
      Six patients with measurable graft contamination became PCR-negative in blood and
      bone marrow within 12 months after autologous stem cell transplantation. Three
      patients free of disease progression (median follow-up of 75 months) are in
      molecular remission. Increasing fractions of RQ-PCR-positive blood and bone
      marrow cells reliably predicted morphological and clinical relapse. In one case,
      both clinical relapse and spontaneous regression were reflected by changes in MRD
      levels. Thus, our RQ-PCR method reproducibly distinguishes different levels of
      MRD.

PMID- 16436634
TI  - Molecular classification of Crohn's disease and ulcerative colitis patients using
      transcriptional profiles in peripheral blood mononuclear cells.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) are common inflammatory bowel
      diseases producing intestinal inflammation and tissue damage. Although emerging
      evidence suggests these diseases are distinct, approximately 10% of patients
      remain classified as indeterminate inflammatory bowel disease even after invasive
      colonoscopy intended for diagnosis. A molecular diagnostic assay using a
      clinically accessible tissue would greatly assist in the classification of these
      diseases. In the present study we assessed transcriptional profiles in peripheral
      blood mononuclear cells from 42 healthy individuals, 59 CD patients, and 26 UC
      patients by hybridization to microarrays interrogating more than 22,000
      sequences. Supervised analysis identified a set of 12 genes that distinguished UC
      and CD patient samples with high accuracy. The alterations in transcript levels
      observed by microarray were verified by real-time polymerase chain reaction. The
      results suggest that a peripheral blood mononuclear cell-based gene expression
      signature can provide a molecular biomarker that can complement the standard
      diagnosis of UC and CD.

PMID- 16436635
TI  - Identification of novel missense mutations of cardiac ryanodine receptor gene in
      exercise-induced sudden death at autopsy.
AB  - Mutations in the cardiac ryanodine type 2 receptor (RyR2) gene are associated
      with catecholaminergic polymorphic ventricular tachycardia. We hypothesized that
      these mutations could be detected at autopsy in cases of exercise-triggered
      sudden death. Fourteen sudden death patients, eight males and six females, were
      studied at autopsy based on apparent sudden cardiac death, without significant
      anatomical abnormalities. The coding regions of arrhythmia genes were amplified
      by polymerase chain reaction and directly sequenced. Three novel RyR2 mutations,
      R414C, F2331S, and R2401L, were identified in three unrelated patients (two males
      and one female; mean age at death, 12 +/- 2 years), all performing strenuous
      activity at the time of death or collapse. These mutations were located in highly
      conserved regions where arrhythmia-linked RyR2 mutations clustered. Although
      G269S in the KVLQT1 gene was detected in a female with known family history of
      syncope and sudden cardiac death, no other mutations were found in any of the 14
      cases, and no other mutations was found in 200 controls. The absence of
      structural cardiac disease in physical activity-induced sudden death and the
      finding of three novel RyR2 mutations suggest that mutation screening in such
      cases should include RyR2.

PMID- 16436636
TI  - Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6
      methylguanine DNA methyltransferase in colorectal cancer.
AB  - Hypermethylation of CpG islands in gene promoter regions is an important
      mechanism of gene inactivation in cancer. Many cellular pathways, including DNA
      repair, are inactivated by this type of epigenetic lesion, resulting in proposed
      mutator phenotypes. Promoter hypermethylation of hMLH1 has been implicated in a
      subset of colorectal cancers that show microsatellite instability (MSI).
      Transcriptional silencing of O6-methylguanine DNA methyltransferase (MGMT) has
      also been described in a variety of neoplasms and has been associated with a
      consequent mutational spectrum. We investigated the relationship between hMLH1
      promoter hypermethylation and MGMT promoter hypermethylation in 110 colorectal
      cancers using methylation-specific polymerase chain reaction. Expression of hMLH1
      and MGMT was assessed by immunohistochemistry. MSI testing was performed using
      the National Cancer Institute consensus panel of five microsatellite markers.
      Promoter hypermethylation of hMLH1 was detected in 12% of tumors. This was
      significantly associated with the MSI-high phenotype (P < 0.01) and loss of hMLH1
      expression (P < 0.01). Methylation of the MGMT promoter was detected in 43% of
      tumors, which were mostly microsatellite stable or MSI-low (P = 0.041) and showed
      loss of MGMT expression (P < 0.01). We demonstrated an inverse relationship
      between hMLH1 promoter hypermethylation and MGMT promoter hypermethylation (P =
      0.041), suggesting that a number of distinct hypermethylation-associated pathways
      may exist in colorectal cancer.

PMID- 16436637
TI  - Multiple gene expression analyses in paraffin-embedded tissues by TaqMan low
      density array: Application to hedgehog and Wnt pathway analysis in ovarian
      endometrioid adenocarcinoma.
AB  - Recent studies have shown the hedgehog and Wnt families of signaling proteins to
      be associated with tumor initiation, growth, and survival. However, these
      pathways remain unexplored in ovarian endometrioid adenocarcinoma (OEA). Here, we
      describe a novel TaqMan low-density array to examine the expression of 26 and 20
      genes in the hedgehog and Wnt pathways, respectively, in six matched snap-frozen
      and formalin-fixed, paraffin-embedded (FPE) OEA specimens. Expression values were
      normalized to uninvolved ovarian epithelium. Gene expression in matched frozen
      and FPE tissues demonstrated significant concordance (r = 0.92, P < 0.0001).
      However, comparison of amplified and unamplified RNA from frozen OEA tissues
      revealed an altered molecular profile in amplified RNA. Amplification of RNA from
      FPE tissues was not successful. The expression of Desert hedgehog (DHH), Indian
      hedgehog (IHH), Hedge-hog interacting protein (HHIP), Wnt10B, Wnt9B, and Wnt
      inhibitory factor (WIF1) were tumor-specific with no detectable expression in
      normal ovarian epithelium. In addition, several genes were significantly (P <
      0.025) down-regulated in OEA, including cyclin E2, Porcupine, c-Myc, and Axin 2
      (4.8-, 3.6-, 2.9-, and 1.9-fold, respectively). TaqMan low-density array provides
      an effective multivariate technique for examining gene expression in RNA isolated
      from either snap-frozen or archival FPE tissues and can identify tumor-specific
      genes, possibly leading to novel treatments.

PMID- 16436638
TI  - Mutation screening in juvenile polyposis syndrome.
AB  - Juvenile polyposis syndrome (JPS) is an autosomal dominant cancer predisposition
      syndrome characterized by congenital anomalies, hamartomatous polyps in the
      gastrointestinal tract, and the development of tumors in these tissues. The
      diagnosis of JPS is often difficult because of the phenotypic overlap with other
      hamartomatous polyposis syndromes. Germline mutations have been identified in
      MADH4 and BMPR1A, aiding in presymptomatic genetic testing. In this study, we
      describe the results from 3 years of molecular diagnostic screening in JPS.
      Seventy unrelated individuals referred to our lab for JPS testing were examined
      through the sequence analysis of coding regions and exon-intron boundaries in
      both genes. Germline mutations were identified in 30% of cases, with 11.4% in
      BMPR1A and 18.6% in MADH4. All mutation-positive individuals were negative for
      cancer at testing, and a single pulmonary valve stenosis was the only congenital
      anomaly reported. A majority of mutations identified were novel including the
      first splice site alteration in MADH4. Based on the limited number of exons in
      each gene, low polymorphism frequency, and high frequency of frameshift or
      nonsense mutations identified, direct sequence analysis is a suitable methodology
      for mutation screening if all coding regions and exon-intron boundaries are
      examined in both genes.

PMID- 16436639
TI  - Multiplexed detection of anthrax-related toxin genes.
AB  - Simultaneous analysis of three targets in three colors on any real-time
      polymerase chain reaction (PCR) instrument would increase the flexibility of real
      time PCR. For the detection of Bacillus strains that can cause inhalation anthrax
      related illness, this ability would be valuable because two plasmids confer
      virulence, and internal positive controls are needed to monitor the testing in
      cases lacking target-specific signals. Using a real-time PCR platform called
      MultiCode-RTx, multiple assays were developed that specifically monitor the
      presence of Bacillus anthracis-specific virulence plasmid-associated genes. In
      particular for use on LightCycler-1, two triplex RTx systems demonstrated high
      sensitivity with limits of detection nearing single-copy levels for both
      plasmids. Specificity was established using a combination of Ct values and
      correct amplicon melting temperatures. All reactions were further verified by
      detection of an internal positive control. For these two triplex RTx assays, the
      analytical detection limit was one to nine plasmid copy equivalents, 100%
      analytical specificity with a 95% confidence interval (CI) of 9%, and 100%
      analytical sensitivity with a CI of 2%. Although further testing using clinical
      or environmental samples will be required to assess diagnostic sensitivity and
      specificity, the RTx platform achieves similar results to those of probe-based
      real-time systems.

PMID- 16436640
TI  - Genotyping of human platelet antigens 1 to 6 and 15 by high-resolution amplicon
      melting and conventional hybridization probes.
AB  - High-resolution melting techniques are a simple and cost-effective alternative to
      other closed-tube genotyping methods. Here, we genotyped human platelet antigens
      (HPAs) 1 to 6 and 15 by high-resolution melting methods that did not require
      labeled probes. Conventional melting analysis with hybridization probes
      (HybProbes) was also performed at each locus. HybProbe assays were performed
      individually, whereas amplicon melting (HPAs 1 to 5 and 16) and unlabeled probe
      (HPA 6) assays were duplexed when possible. At all loci for each method, both
      homozygous and heterozygous genotypes were easily identified. We analyzed 100
      blinded clinical samples (33 amniotic fluid, 12 cultured amniocytes, and 55 blood
      samples) for all 7 single-nucleotide polymorphisms (SNPs) by each method.
      Genotype assignments could be made in 99.0% of the SNPs by high-resolution
      melting and in 98.7% of the SNPs with HybProbes with an overall genotype
      concordance of 98.8%. Errors included two sample misidentifications and six
      incorrect assignments that were all resolved by repeating the analysis.
      Advantages of high-resolution melting include rapid assay development and
      execution, no need for modified oligonucleotides, and similar accuracy in
      genotyping compared with other closed-tube melting methods.

PMID- 16436642
TI  - DNA and RNA references for qRT-PCR assays in exfoliated cervical cells.
AB  - The noncritical use of housekeeping genes, RNA mass, or cell number for
      normalization in quantitative reverse transcriptase-polymerase chain reaction
      (qRT-PCR) assays has come under scrutiny in recent years, highlighting the need
      to evaluate references in the immediate context of the relevant samples and
      experimental design. The purpose of this study was to select appropriate
      references for normalizing qRT-PCR assays of gene expression in exfoliated
      cervical cells. We used total nucleic acid extracts from 30 samples, representing
      the full spectrum of pre-invasive cervical neoplasia. We determined the DNA
      content by quantitative PCR for the single-copy gene beta-globin and total RNA
      content using quantitative image analysis of ribosomal bands. In addition, qRT
      PCR for 13 candidate housekeeping genes was performed. We used two analysis
      methods, geNorm and Norm-Finder, to identify the best combination of reference
      genes and then correlated housekeeping gene expression with DNA content and gel
      representation of ribosomal RNA. ACTB was the most stable single gene. The
      addition of PGK1 and RPLP0 increased the robustness in qRT-PCR applications not
      stratified by disease. These genes also showed the highest correlation with DNA
      contents in the same samples. If special attention to intraepithelial lesions is
      appropriate, RPL4 and PGK1 are recommended as the best combination of two genes.

PMID- 16436641
TI  - Specific detection of cytokeratin 20-positive cells in blood of colorectal and
      breast cancer patients by a high sensitivity real-time reverse transcriptase
      polymerase chain reaction method.
AB  - A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method for
      detection of cytokeratin 20-positive cells in blood characterized by two novel
      features was developed and tested on 99 patients with colorectal cancer, 110 with
      breast cancer, and 150 healthy subjects. To optimize the specificity and
      sensitivity of the method, two novel features were used. First, a primer
      overlapping two adjacent exons was generated to inhibit nonspecific amplification
      both in healthy donors and cancer patients; second, a non-end-point first-round
      amplification was used to increase sensitivity. The number of first-round cycles
      was chosen to reach the highest level of sensitivity while conserving
      quantitative characteristics. PCR efficiency increased from 88.9% in single-round
      RT-PCR to 99.0% in nested real-time RT-PCR. To establish sensitivity and
      specificity of the method, HT29 cells were serially diluted with normal blood.
      Detection limit improved from 100 HT29 cells (single-round RT-PCR) to 1 to 10
      cells (nested real-time RT-PCR) per 3 ml of whole blood. None of the healthy
      subjects was positive, whereas 22 and 29% of all colorectal and breast cancer
      patients, respectively, had cytokeratin 20 cell equivalents in blood. The
      association between cytokeratin 20 cell equivalents and metastasis was
      statistically significant for breast (P = 0.026) but not colorectal cancer
      patients (P = 0.361). Negativity of all 150 healthy controls examined confers
      diagnostic potential to the method.

PMID- 16436643
TI  - A haplotype framework for cystic fibrosis mutations in Iran.
AB  - This is the first comprehensive profile of cystic fibrosis transmembrane
      conductance regulator (CFTR) mutations and their corresponding haplotypes in the
      Iranian population. All of the 27 CFTR exons of 60 unrelated Iranian CF patients
      were sequenced to identify disease-causing mutations. Eleven core haplotypes of
      CFTR were identified by genotyping six high-frequency simple nucleotide
      polymorphisms. The carrier frequency of 2.5 in 100 (1 in 40) was estimated from
      the frequency of heterozygous patients and suggests that contrary to popular
      belief, cystic fibrosis may be a common, under-diagnosed disease in Iran. A
      heterogeneous mutation spectrum was observed at the CFTR locus in 60 cystic
      fibrosis (CF) patients from Iran. Twenty putative disease-causing mutations were
      identified on 64 (53%) of the 120 chromosomes. The five most common Iranian
      mutations together represented 37% of the expected mutated alleles. The most
      frequent mutation, DeltaF508 (p.F508del), represented only 16% of the expected
      mutated alleles. The next most frequent mutations were c.1677del2 (p.515fs) at
      7.5%, c.4041C>G (p.N1303K) at 5.6%, c.2183AA>G (p.684fs) at 5%, and c.3661A>T
      (p.K1177X) at 2.5%. Three of the five most frequent Iranian mutations are not
      included in a commonly used panel of CF mutations, underscoring the importance of
      identifying geographic-specific mutations in this population.

PMID- 16436644
TI  - Large pathogenic expansions in the SCA2 and SCA7 genes can be detected by
      fluorescent repeat-primed polymerase chain reaction assay.
AB  - Large expansions in the SCA2 and SCA7 genes (>100 CAG repeats) have been
      associated with juvenile and infantile forms of cerebellar ataxias that cannot be
      detected using standard polymerase chain reaction (PCR). Here, we describe a
      successful application of the fluorescent short tandem repeat-primed PCR method
      for accurate identification of these expanded repeats. The test is robust,
      reliable, and inexpensive and can be used to screen large series of patients,
      although it cannot give a precise evaluation of the size of the expansion. This
      test may be of practical value in prenatal diagnoses offered to affected or pre
      symptomatic at-risk parents, in which a very large expansion inherited from one
      of the parents can be missed in the fetus by standard PCR.

PMID- 16436645
TI  - Limitations and practical procedure in BclII-Ig heavy chain gene rearrangement
      real-time quantitative polymerase chain reaction.
AB  - Follicular lymphoma is characterized by the t(14;18)(q32;q21) translocation,
      which juxtaposes Ig heavy chain gene (IgH) sequences with the BclII gene. Several
      publications have highlighted the importance of molecular follow-up in follicular
      lymphoma, demonstrating that the detection of cells bearing the BclII-IgH
      rearrangement by real-time quantitative polymerase chain reaction (RQ-PCR) can
      anticipate a clinical relapse. In this context, we developed a BclII-IgH RQ-PCR.
      We began with SYBR Green I detection technology but observed that this system
      does not allow an accurate measurement of the tumor load when working with
      genomic DNA. While we were designing the assay using Taqman technology, Moppett
      et al (Moppett J, van der Velden VHJ, Wijkhuijs AJM, Hancock J, van Dongen JJM,
      Goulden N: Inhibition affecting RQ-PCR-based assessment of minimal residual
      disease in acute lymphoblastic leukemia: reversal by addition of bovine serum
      albumin. Leukemia 2003, 17:268-270) reported PCR inhibition problems in around
      15% of blood and bone marrow samples, affecting the DNA quantification and thus
      the assessment of minimal residual disease. They demonstrated that this PCR
      inhibition could be partially resolved by adding nonacetylated bovine serum
      albumin. In our studies, we observed the same phenomenon in a single follicular
      lymphoma case and extended our study to other available cases. As a result, we
      suggest a new RQ-PCR procedure that is based on Taqman probe technology and that
      takes into account the PCR inhibition problems, making this assay more reliable
      in a routine molecular laboratory.

PMID- 16436646
TI  - Detection of an apparent homozygous 3120G>A cystic fibrosis mutation on a routine
      carrier screen.
AB  - A 28-year-old Caucasian female with no personal or family history of cystic
      fibrosis (CF) presented for preconception counseling and screening. Cystic
      fibrosis transmembrane conductance regulator (CFTR) mutation analysis using the
      Inno-LiPa CFTR assay revealed lack of hybridization for both the wild-type and
      mutant oligonucleotides for 3120+1G>A. This region was sequenced, and an apparent
      homozygous 3120G>A mutation was detected. Additional testing revealed an abnormal
      sweat chloride (77 mmol/L). Review of systems was essentially unremarkable with
      an absence of sinus symptoms, occasional nonproductive cough, and no features of
      malabsorption. Physical examination, chest X-ray, and pulmonary function tests
      were within normal limits. Only two other patients (siblings) with homozygous
      3120G>A mutations have been reported (http://www.genet.sickkids.on.ca/cftr/).
      Both siblings had pancreatic insufficiency, mild pulmonary symptoms, and abnormal
      sweat chloride levels. Our findings suggest that a homozygous mutation of a G>A
      conversion at 3120 is associated with abnormal CFTR function and either a mild
      form of CF or no overt symptoms of disease, emphasizing the difficulties in
      assigning genotype/phenotype correlation.

PMID- 16436647
TI  - Haptoglobin and the development of cerebral artery vasospasm after subarachnoid
      hemorrhage.
AB  - BACKGROUND: Vasospasm is a prolonged constriction of a cerebral artery that is
      induced by hemoglobin after subarachnoid hemorrhage (SAH). The subarachnoid blood
      clot also contains the protein haptoglobin, which acts to neutralize hemoglobin.
      Because the haptoglobin alpha gene is dimorphic, a person can expresses only one
      of three types of haptoglobin (alpha1-alpha1, alpha1-alpha2, or alpha2-alpha2)
      depending on the alpha subunit genes he or she inherits. Each of these three
      haptoglobin types has different antihemoglobin activities; therefore, haptoglobin
      may influence the development of vasospasm differently in various patients with
      SAH. OBJECTIVE: To determine whether SAH patients who have haptoglobin containing
      the alpha2 subunit would be more likely to develop vasospasm than would be SAH
      patients who have haptoglobin alpha1-alpha1. METHODS AND RESULTS: A total of 32
      patients with Fisher Grade 3 SAH were enrolled in this study. Haptoglobin type
      was determined by polyacrylamide gel electrophoresis. The primary measure for
      vasospasm was increased blood flow velocities as detected by daily transcranial
      Doppler ultrasonography (TCD). The authors found that only 2 of 9 patients with
      haptoglobin alpha1-alpha1 (22%) had development of "possible" vasospasm as
      measured by TCD, whereas 20 of 23 patients with the haptoglobin alpha2 subunit
      (either the alpha1-alpha2 or alpha2-alpha2 haptoglobin types) had development of
      "possible" vasospasm (87%). The secondary measure for vasospasm was cerebral
      angiography performed between 3 and 14 days after SAH. Similar results (17% vs
      56%) were seen between these groups in those patients who underwent cerebral
      angiography, although its inconsistent use limited the strength of the
      statistical comparison. CONCLUSIONS: Haptoglobins containing the alpha2 subunit
      seem to be associated with a higher rate of vasospasm than is haptoglobin alpha1
      alpha1.

PMID- 16436648
TI  - Topiramate in essential tremor: a double-blind, placebo-controlled trial.
AB  - BACKGROUND: Essential tremor is most prevalent and most disabling in older
      patients. Additional therapies are required for patients with an inadequate
      response or intolerable side effects. In small trials, topiramate appeared to be
      beneficial in essential tremor. METHODS: In this multicenter, double-blind,
      placebo-controlled, parallel-design trial, patients with moderate to severe
      essential tremor of the upper limbs were randomized to 24 weeks of treatment with
      placebo or topiramate (target dose, 400 mg/day) as monotherapy or as an adjunct
      to one antitremor medication. The primary efficacy variable was the final visit
      tremor score based on the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). RESULTS:
      The intent-to-treat population was 208 patients (topiramate, 108; placebo, 100).
      The final visit score (last observation carried forward) was lower in the
      topiramate group than with placebo (p < 0.001). Mean percentage improvement in
      overall TRS scores was 29% with topiramate at a mean final dose of 292 mg/day and
      16% with placebo (p < 0.001). Topiramate was associated with greater improvement
      in function and disability (p = 0.001). A between-group difference (p < 0.001)
      was observed at the first on-treatment visit at 4 weeks when the target
      topiramate dose was 100 mg/day (mean achieved dose, 62 +/- 9 mg/day). The most
      common treatment-limiting adverse events in topiramate-treated patients were
      paresthesia (5%), nausea (3%), concentration/attention difficulty (3%), and
      somnolence (3%). Adverse events were treatment limiting in 31.9% of topiramate
      patients and 9.5% of placebo patients. CONCLUSIONS: Topiramate was effective in
      the treatment of moderate to severe essential tremor. Tremor reduction was
      accompanied by functional improvements, such as in motor tasks, writing, and
      speaking.

PMID- 16436649
TI  - IM interferon beta-1a delays definite multiple sclerosis 5 years after a first
      demyelinating event.
AB  - BACKGROUND: The Controlled High Risk Subjects Avonex Multiple Sclerosis
      Prevention Study (CHAMPS) showed that IM interferon beta-1a (IFNbeta-1a)
      significantly slows the rate of development of clinically definite multiple
      sclerosis (CDMS) over 2 years in high-risk patients who experience a first
      clinical demyelinating event. This report highlights the primary results of a 5
      year, open-label extension of CHAMPS (the Controlled High Risk Avonex Multiple
      Sclerosis Prevention Study in Ongoing Neurologic Surveillance [CHAMPIONS Study]).
      OBJECTIVE: To determine if the benefits of IFNbeta-1a observed in CHAMPS are
      sustained for up to 5 years. METHODS: CHAMPS patients at participating CHAMPIONS
      sites were enrolled in the study. All patients were offered, but not required to
      take, IFNbeta-1a 30 microg IM once weekly for up to 5 years (from CHAMPS
      randomization). Patients who received placebo in CHAMPS were considered the
      delayed treatment (DT) group, and patients who received IFNbeta-1a in CHAMPS were
      considered the immediate treatment (IT) group. The primary outcome measure was
      the rate of development of CDMS. Additional outcomes included disease state
      classification at 5 years, annualized relapse rates, disability level at 5 years
      (Expanded Disability Status Scale), and MRI measures at 5 years. RESULTS: Fifty
      three percent (203/383) of patients enrolled in CHAMPIONS (n = 100, IT group; n =
      103, DT group) and 64% (32/50) of CHAMPS study sites participated in CHAMPIONS.
      The median time to initiation of IFNbeta-1a therapy in the DT group was 29
      months. The cumulative probability of development of CDMS was significantly lower
      in the IT group compared with the DT group (5-year incidence 36 +/- 9 vs 49 +/-
      10%; p = 0.03). Multivariate analysis suggested that the only factors
      independently associated with an increased rate of development of CDMS were
      randomization to the DT group and younger age at onset of neurologic symptoms.
      Few patients in either group developed major disability within 5 years.
      CONCLUSIONS: These results support the use of IM interferon beta-1a after a first
      clinical demyelinating event and indicate that there may be modest beneficial
      effects of immediate treatment compared with delayed initiation of treatment.

PMID- 16436650
TI  - Cerebrovascular reactivity and vasospasm after subarachnoid hemorrhage: a pilot
      study.
AB  - The authors performed serial transcranial Doppler (TCD) and carbon dioxide
      reactivity (CO2R) testing in 20 aneurysmal subarachnoid hemorrhage patients to
      determine whether impaired cerebrovascular reactivity was associated with
      symptomatic vasospasm. Symptomatic vasospasm occurred in 9 of 14 patients with
      abnormal CO2R and in none of 6 patients with preserved reactivity (p = 0.011).
      Abnormal CO2R preceded the onset of vasospasm in 7 of 9 patients. Abnormal
      standard TCD testing was not associated with vasospasm.

PMID- 16436651
TI  - Carcinogenesis and metastasis now in the third dimension--what's in it for
      pathologists?

PMID- 16436652
TI  - The tumor suppressor von Hippel-Lindau gene product and metastasis: new thoughts
      on an old molecule.

PMID- 16436653
TI  - Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis.
AB  - Hepatitis C virus (HCV) infection is frequently complicated by glomerulonephritis
      with immune complexes containing viral RNA. We examined the potential influence
      of Toll-like receptors (TLRs), specifically TLR3 recognition of viral dsRNA
      exemplified by polyriboinosinic:polyribocytidylic acid [poly(I:C) RNA]. Normal
      human kidney stained positive for TLR3 on mesangial cells (MCs), vascular smooth
      muscle cells, and collecting duct epithelium. Cultured MCs have low TLR3 mRNA
      levels with predominant intracellular protein localization, which was increased
      by tumor necrosis factor-alpha, interleukin (IL)-1beta, interferon (IFN)-gamma,
      and the TLR3 ligand poly(I:C) RNA. Poly(I:C) RNA stimulation of MCs increased
      mRNA and protein synthesis of IL-6, IL-1beta, M-CSF, IL-8/CXCL8, RANTES/CCL5, MCP
      1/CCL2, and ICAM-I; it also increased anti-proliferative and proapoptotic
      effects, the latter of which was decreased by inhibiting caspase-8. In
      microdissected glomeruli of normal and non-HCV membranoproliferative
      glomerulonephritis biopsies, TLR3 mRNA expression was low. In contrast TLR3 mRNA
      expression was significantly increased in hepatitis C-positive glomerulonephritis
      and was associated with enhanced mRNA for RANTES/CCL5 and MCP-1/CCL2. We
      hypothesize that immune complexes containing viral RNA activate mesangial TLR3
      during HCV infection, thereby contributing to chemokine/cytokine release and
      effecting proliferation and apoptosis. Thus, TLR3 expression on renal cells, and
      especially MCs, may establish a link between viral infections and glomerular
      diseases.

PMID- 16436654
TI  - Autophagic cardiomyocyte death in cardiomyopathic hamsters and its prevention by
      granulocyte colony-stimulating factor.
AB  - In UM-X7.1 hamster model of human dilated cardiomyopathy, heart failure
      progressively develops and causes 50% mortality by 30 weeks of age. Through
      ultrastructural analysis, we found that many cardiomyocytes of this model contain
      typical autophagic vacuoles including degraded mitochondria, glycogen granules,
      and myelin-like figures. In addition, ubiquitin, cathepsin D, and Rab7 were
      overexpressed as determined by immunoassays. Importantly, most cardiomyocytes
      with leaky plasma membranes were positive for cathepsin D, suggesting a direct
      link between autophagic degeneration and cell death. Meanwhile, cardiomyocyte
      apoptosis appeared insignificant. Granulocyte colony-stimulating factor (10
      microg/kg/day), injected 5 days/week from 15 to 30 weeks of age, improved
      survival among 30-week-old hamsters (100% versus 53% in the untreated hamsters, P
      < 0.0001); ventricular function and remodeling, increased cardiomyocyte size, and
      reduced myocardial fibrosis followed by a dramatic reduction in the autophagic
      findings were also seen. Granulocyte colony-stimulating factor also down
      regulated tumor necrosis factor-alpha and increased activities of Akt signal
      transducer and activator of transcription-3, and matrix metalloproteinases.
      However, there was no clear evidence of transdifferentiation from bone marrow
      cells into cardiomyocytes. In conclusion, autophagic death is important for
      cardiomyocyte loss in the cardiomyopathic hamster, and the beneficial effect of
      granulocyte colony-stimulating factor acts mainly via an anti-autophagic
      mechanism rather than anti-apo-ptosis or regeneration.

PMID- 16436655
TI  - Ca2+-dependent cytoprotective effects of ursodeoxycholic and tauroursodeoxycholic
      acid on the biliary epithelium in a rat model of cholestasis and loss of bile
      ducts.
AB  - Chronic cholestatic liver diseases are characterized by impaired balance between
      proliferation and death of cholangiocytes, as well as vanishing of bile ducts and
      liver failure. Ursodeoxycholic acid (UDCA) is a bile acid widely used for the
      therapy of cholangiopathies. However, little is known of the cytoprotective
      effects of UDCA on cholangiocytes. Therefore, UDCA and its taurine conjugate
      tauroursodeoxycholic acid (TUDCA) were administered in vivo to rats
      simultaneously subjected to bile duct ligation and vagotomy, a model that induces
      cholestasis and loss of bile ducts by apoptosis of cholangiocytes. Because these
      two bile acids act through Ca2+ signaling, animals were also treated with
      BAPTA/AM (an intracellular Ca2+ chelator) or Go6976 (a Ca2+-dependent protein
      kinase C-alpha inhibitor). The administration of UDCA or TUDCA prevented the
      induction of apoptosis and the loss of proliferative and functional responses
      observed in the bile duct ligation-vagotomized rats. These effects were
      neutralized by the simultaneous administration of BAPTA/AM or Go6976. UDCA and
      TUDCA enhanced intracellular Ca2+ and IP3 levels, together with increased
      phosphorylation of protein kinase C-alpha. Parallel changes were observed
      regarding the activation of the MAPK and PI3K pathways, changes that were
      abolished by addition of BAPTA/AM or Go6976. These studies provide information
      that may improve the response of cholangiopathies to medical therapy.

PMID- 16436656
TI  - Lithocholic acid feeding induces segmental bile duct obstruction and destructive
      cholangitis in mice.
AB  - We determined the mechanisms of hepatobiliary injury in the lithocholic acid
      (LCA)-fed mouse, an increasingly used model of cholestatic liver injury. Swiss
      albino mice received control diet or 1% (w/w) LCA diet (for 1, 2, and 4 days),
      followed by assessment of liver morphology and ultrastructure, tight junctions,
      markers of fibrosis and key proteins of hepatobiliary function, and bile flow and
      composition. As expected LCA feeding led to bile infarcts, which were followed by
      a destructive cholangitis with activation and proliferation of periductal
      myofibroblasts. At the ultrastructural level, small bile ducts were frequently
      obstructed by crystals. Biliary-excreted fluorescence-labeled ursodeoxycholic
      acid accumulated in bile infarcts, whereas most infarcts did not stain with India
      ink injected into the common bile duct; both findings are indicative of partial
      biliary obstruction. Expression of the main basolateral bile acid uptake proteins
      (sodium-taurocholate cotransporter and organic anion-transporting polypeptide 1)
      was reduced, the canalicular transporters bile salt export pump and multidrug
      related protein 2 were preserved, and the basolateral transporter multidrug
      related protein 3 and the detoxifying enzyme sulfotransferase 2a1 were induced.
      Thus, we demonstrate that LCA feeding in mice leads to segmental bile duct
      obstruction, destructive cholangitis, periductal fibrosis, and an adaptive
      transporter and metabolic enzyme response.

PMID- 16436657
TI  - Consequences of copper accumulation in the livers of the Atp7b-/- (Wilson disease
      gene) knockout mice.
AB  - Wilson disease is a severe genetic disorder associated with intracellular copper
      overload. The affected gene, ATP7B, has been identified, but the molecular events
      leading to Wilson disease remain poorly understood. Here, we demonstrate that
      genetically engineered Atp7b-/- mice represent a valuable model for dissecting
      the disease mechanisms. These mice, like Wilson disease patients, have
      intracellular copper accumulation, low-serum oxidase activity, and increased
      copper excretion in urine. Their liver pathology developed in stages and was
      determined by the time of exposure to elevated copper rather than copper
      concentration per se. The disease progressed from mild necrosis and inflammation
      to extreme hepatocellular injury, nodular regeneration, and bile duct
      proliferation. Remarkably, all animals older than 9 months showed regeneration of
      large portions of the liver accompanied by the localized occurrence of
      cholangiocarcinoma arising from the proliferating bile ducts. The biochemical
      characterization of Atp7b-/- livers revealed copper accumulation in several cell
      compartments, particularly in the cytosol and nuclei. The increase in nuclear
      copper is accompanied by marked enlargement of the nuclei and enhanced DNA
      synthesis, with these changes occurring before pathology development. Our results
      suggest that the early effects of copper on cell genetic material contribute
      significantly to pathology associated with Atp7b inactivation.

PMID- 16436658
TI  - Autoamplification of tumor necrosis factor-alpha: a potential mechanism for the
      maintenance of elevated tumor necrosis factor-alpha in male but not female obese
      mice.
AB  - Although tumor necrosis factor-alpha (TNF-alpha) is elevated in adipose tissue in
      obesity and may contribute to the cardiovascular and metabolic risks associated
      with this condition, the mechanisms leading to elevated TNF-alpha remain elusive.
      We hypothesized that autoamplification of TNF-alpha contributes to the
      maintenance of elevated TNF-alpha in obesity. Treatment of 3T3-L1 adipocytes with
      TNF-alpha, or injection of TNF-alpha into C57BL/6J mice, up-regulated TNF-alpha
      mRNA in adipocytes and in adipose tissues, respectively. Ob/ob male but not
      female mice lacking TNF-alpha receptors showed significantly lower levels of
      adipose TNF-alpha mRNA when compared with TNF-alpha receptor-expressing ob/ob
      mice. Thus, the lack of endogenous TNF-alpha signaling reduced adipose TNF-alpha
      mRNA in ob/ob male mice. Additionally, hyperinsulinemia potentiated this TNF
      alpha-mediated autoamplification response in adipose tissues and in adipocytes in
      a synergistic and dose-dependent manner. Studies in which TNF-alpha was injected
      into lean mice lacking individual TNF-alpha receptors indicated that TNF-alpha
      autoamplification in adipose tissues was mediated primarily via the p55 TNF-alpha
      receptor whereas the p75 TNF-alpha receptor appeared to augment this response.
      Finally, TNF-alpha autoamplification in adipocytes occurred via the protein
      kinase C signaling pathway and the transcription factor nuclear factor-kappaB.
      Thus, TNF-alpha can positively autoregulate its own biosynthesis in adipose
      tissue, contributing to the maintenance of elevated TNF-alpha in obesity.

PMID- 16436659
TI  - Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis
      factor-alpha and interleukin-1beta in first trimester human decidual cells:
      implications for preeclampsia.
AB  - The current study describes a statistically significant increase in macrophages
      (CD68-positive cells) in the decidua of preeclamptic patients. To elucidate the
      regulation of this monocyte infiltration, expression of monocyte chemoattractant
      protein-1 (MCP-1) was assessed in leukocyte-free first trimester decidual cells.
      Confluent decidual cells were primed for 7 days in either estradiol or estradiol
      plus medroxyprogesterone acetate to mimic the decidualizing steroidal milieu of
      the luteal phase and early pregnancy. The medium was exchanged for a serum-free
      defined medium containing corresponding steroids +/- tumor necrosis factor (TNF)
      alpha or interleukin (IL)-1beta. After 24 hours, enzyme-linked immunosorbent
      assay measurements indicated that the addition of medroxyprogesterone acetate did
      not affect MCP-1 output, whereas 10 ng/ml of TNF-alpha or IL-1beta increased
      output by 83.5-fold +/- 20.6 and 103.1-fold +/- 14.7, respectively (mean +/- SEM,
      n = 8, P < 0.05). Concentration-response comparisons revealed that even 0.01
      ng/ml of TNF-alpha or IL-1beta elevated MCP-1 output by more than 15-fold.
      Western blotting confirmed the enzyme-linked immunosorbent assay results, and
      quantitative reverse transcriptase-polymerase chain reaction confirmed
      corresponding effects on MCP-1 mRNA levels. The current study demonstrates that
      TNF-alpha and IL-1beta enhance MCP-1 in first trimester decidua. This finding
      suggests a mechanism by which recruitment of excess macrophages to the decidua
      impairs endovascular trophoblast invasion, the primary placental defect of
      preeclampsia.

PMID- 16436661
TI  - CD8 T cells modulate CD4 T-cell and eosinophil-mediated pulmonary pathology in
      pneumocystis pneumonia in B-cell-deficient mice.
AB  - Pneumocystis spp. pneumonia (PCP) in humans and in surrogate animal species
      typically occurs in the absence of CD4 T cells, as takes place during acquired
      immune deficiency syndrome. However, patients treated with highly active anti
      retroviral therapy sometimes exhibit an exacerbation of diseases such as PCP that
      coincides with resurgent CD4 T cells, a phenomenon known as immune reconstitution
      disease. We used an animal model of PCP using the B-cell-deficient muMT mouse
      together with antibody-mediated depletion of various T-cell subsets to examine
      the role of CD4 and CD8 T cells in the development of pathology in PCP. Although
      overt pathology occurs in the presence of CD4 T cells only, CD8 T cells only, or
      both, pulmonary injury occurs via different paths, depending on the complement of
      T cells present. Surprisingly, profound damage occurred when only CD4 T cells
      were present, and this pathology coincided with enhanced recruitment and
      activation of eosinophils and strong type 2 cytokine polarization in the alveolar
      environment. In addition, CD8 T cells can act to moderate this CD4 T cell
      mediated pathology, possibly by increasing the ratio of putative CD25+ suppressor
      CD4 T cells to CD25- effector CD4 T cells.

PMID- 16436660
TI  - The class 6 semaphorin SEMA6A is induced by interferon-gamma and defines an
      activation status of langerhans cells observed in pathological situations.
AB  - Originally implicated in axon guidance, semaphorins represent a large family of
      molecules that are now known to be expressed in the immune system. Among
      different semaphorins tested by reverse transcriptase-polymerase chain reaction
      in human immune cells, the expression of class 6 transmembrane semaphorin SEMA6A
      was restricted to dendritic cells (DCs). Using in-house generated monoclonal
      antibodies, SEMA6A expression appeared further restricted to Langerhans cells
      (LCs). In vivo, SEMA6A mRNA was expressed in freshly isolated skin LCs but SEMA6A
      protein was not detectable on normal skin and tonsillar epithelium. Of interest,
      SEMA6A protein was strongly expressed on skin and bone LCs and on LCs in draining
      lymph nodes from patients with LC histiocytosis or dermatopathic lymphadenitis,
      respectively, representing two inflammatory conditions in which LCs display an
      immature DC-LAMP(low), CD83(low), and CCR7+ phenotype. SEMA6A expression was low
      in resting LCs generated in vitro and was enhanced by interferon (IFN)-gamma but
      not by interleukin-4, interleukin-10, IFN-alpha/beta, or lipopolysaccharide. Most
      IFN-gamma-induced SEMA6A-positive cells remained immature with low CD83 and DC
      LAMP/CD208 expression, but they expressed CCR7 and responded to macrophage
      inflammatory protein-3beta (MIP-3beta/CCL19). The expression of SEMA6A, for which
      the ligand and function remain unknown, may therefore identify an alternative IFN
      gamma-dependent activation status of LCs in vivo.

PMID- 16436662
TI  - A soluble BAFF antagonist, BR3-Fc, decreases peripheral blood B cells and
      lymphoid tissue marginal zone and follicular B cells in cynomolgus monkeys.
AB  - BAFF (also known as BLyS), a member of the tumor necrosis factor superfamily,
      plays a critical role in the maturation and development of B cells. BAFF has
      three receptors on B cells, the most crucial of which is BR3. In this study, we
      demonstrate the biological outcome of BAFF blockade in cynomolgus monkeys using a
      soluble fusion protein consisting of human BR3 and human IgG1 Fc. In vitro, BR3
      Fc blocked BAFF-mediated survival and proliferation of cynomolgus monkey B cells.
      Weekly treatment of cynomolgus monkeys with BR3-Fc for 13 to 18 weeks resulted in
      significant B-cell reduction in the peripheral blood and in lymphoid organs.
      CD21(high) B cells in lymphoid tissues, a subset analogous to human marginal zone
      B cells, expressed nearly twofold higher BR3 levels than did CD21(med) B cells.
      Lymphoid tissue flow cytometric analysis showed that BR3-Fc reduced this
      CD21(high) B-cell subset to a greater extent than it reduced CD21(med) B cells.
      Dual-label immunohistochemistry and morphometric image analysis supported these
      results by demonstrating that BR3-Fc reduced a significant proportion of the B
      cells within the splenic inner and outer marginal zones. These findings should
      prove very useful in guiding the desired therapeutic use of BR3-Fc for autoimmune
      diseases in the clinic.

PMID- 16436663
TI  - Elastin calcification in the rat subdermal model is accompanied by up-regulation
      of degradative and osteogenic cellular responses.
AB  - Calcification of vascular elastin occurs in patients with arteriosclerosis, renal
      failure, diabetes, and vascular graft implants. We hypothesized that pathological
      elastin calcification is related to degenerative and osteogenic mechanisms. To
      test this hypothesis, the temporal expression of genes and proteins associated
      with elastin degradation and osteogenesis was examined in the rat subdermal
      calcification model by quantitative real-time reverse transcription-polymerase
      chain reaction and specific protein assays. Purified elastin implanted
      subdermally in juvenile rats exhibited progressive calcification in a time
      dependent manner along with fibroblast and macrophage infiltration. Reverse
      transcription-polymerase chain reaction analysis showed that relative gene
      expression levels of matrix metalloproteinases (MMP-2 and MMP-9) and transforming
      growth factor-beta1 were increased in parallel with calcification. Gelatin
      zymography showed strong MMP activities at early time points, which were
      associated with high levels of soluble elastin peptides. Gene expression of core
      binding factor alpha-1, an osteoblast-specific transcription factor, increased in
      parallel with elastin calcification and attained approximately 9.5-fold higher
      expression at 21 days compared to 3 days after implantation. Similarly, mRNA
      levels of the bone markers osteopontin and alkaline phosphatase also increased
      progressively, but osteocalcin levels remained unchanged. We conclude that
      degenerative and osteogenic processes may be involved in elastin calcification.

PMID- 16436665
TI  - Homeobox gene HLX1 expression is decreased in idiopathic human fetal growth
      restriction.
AB  - Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in
      which the fetus fails to achieve its full growth potential in utero. Identifiable
      causes of FGR account for approximately 30% of cases, but the remainder are
      idiopathic and are frequently associated with placental malfunction. Previously,
      we isolated the homeobox gene HLX1 and provided evidence for a regulatory role in
      normal placental development. Here, we investigated whether placental HLX1
      expression levels are changed in placentas from idiopathic FGR pregnancies. Real
      time polymerase chain reaction quantitation showed reduced HLX1 mRNA levels with
      advancing gestation age (preterm control placentas, 27 to 35 weeks, 1.1 +/- 0.3,
      n = 13, versus term placentas 36 to 41 weeks, 0.74 +/- 0.02, n = 12, P < 0.005).
      FGR-affected placentas had significantly lower levels of HLX1 expression compared
      with gestation age-matched controls (0.36 +/- 0.07 versus 1.05 +/- 0.2, n = 25, P
      < 0.001). Immunoblotting with a rabbit polyclonal HLX1 antibody revealed reduced
      levels of HLX1 in FGR-affected placentas compared with controls (481.07 +/- 12.3
      versus 2766.7 +/- 30.3, n = 10, P < 0.001). Immunohistochemistry showed a
      qualitative decrease in HLX1 immunoreactivity in FGR-affected term placentas
      compared with controls. This is the first demonstration that a homeobox
      transcriptional regulator shows altered expression in an important human
      placental disorder, suggesting that decreased HLX1 levels contribute to the
      abnormalities in placental developmental seen in idiopathic FGR.

PMID- 16436664
TI  - Increased expression of integrin alphavbeta5 induces the myofibroblastic
      differentiation of dermal fibroblasts.
AB  - The biological effect of cytokines is mainly determined by the cytokine-receptor
      interaction, which is modulated by the concentration and the activity of
      cytokines and/or their receptors. Because alphav-containing integrins can bind to
      and/or activate latent TGF-beta, these integrins have been thought to be involved
      in the pathogenesis of fibrotic disorders. Our recent observations that
      alphavbeta5 is up-regulated in scleroderma fibroblasts and that the transient
      overexpression of alphavbeta5 increases the human alpha2(I) collagen gene
      expression in normal fibroblasts suggest the involvement of alphavbeta5 in the
      self-activation system in scleroderma fibroblasts. In this study, we established
      stable transfectants with alphavbeta5 using normal dermal fibroblasts and
      demonstrated that such cells differentiated into myofibroblasts by the
      stimulation of autocrine TGF-beta. This observation is explained by 1)
      alphavbeta5 recruiting latent TGF-beta1 on the cell surface, 2) endogenous active
      TGF-beta localizing on the cell surface, and 3) alphavbeta5 interacting with TGF
      beta receptors. Furthermore, blockade of alphavbeta5 reversed the myofibroblastic
      phenotype in scleroderma fibroblasts. These data identify a novel mechanism for
      the establishment of autocrine TGF-beta signaling in dermal fibroblasts by the up
      regulation of alphavbeta5 and suggest the possibility of regulating fibrotic
      disorders, especially scleroderma, by targeting this integrin.

PMID- 16436666
TI  - Failure of elastic fiber homeostasis leads to pelvic floor disorders.
AB  - Pelvic floor disorders, a group of conditions affecting adult women, include
      pelvic organ prolapse and urinary incontinence. Vaginal childbirth and aging are
      risk factors, and weakening of the pelvic support structures is a major aspect of
      the pathology. However, the underlying molecular mechanism remains unknown.
      Female reproductive organs are rich in elastic fibers that turn over slowly in
      most adult tissues but undergo massive remodeling in the reproductive organs
      through pregnancy and birth. Here we show that a failure to maintain elastic
      fiber homeostasis in mice causes pelvic floor disorders. Lysyl oxidase-like-1
      (LOXL1), a protein essential for the postnatal deposition of elastic fibers, was
      highly expressed and regulated in the reproductive tract of the mouse, and its
      expression was diminished during aging. LOXL1 deficiency caused an inability of
      reproductive tissues to replenish elastic fibers after parturition, leading to
      pelvic organ prolapse, weakening of the vaginal wall, paraurethral pathology, and
      lower urinary tract dysfunction. These data demonstrate the importance of elastic
      fibers for maintaining structural and functional integrity of the female pelvic
      floor. Our findings raise the possibility that a failure of elastic fiber
      homeostasis, either due to genetic predisposition or advancing age, could
      underlie the etiology of pelvic floor dysfunction in women.

PMID- 16436668
TI  - Canine cranial reconstruction using autologous bone marrow stromal cells.
AB  - Limited-sized transplants of culture-expanded autologous or allogeneic bone
      marrow stromal cells (BMSCs) form cortico-cancellous bone in rodent models.
      Initiation of clinical studies using autologous BMSC transplantation requires
      effective bone formation among sizable transplants in a large animal model as
      well as noninvasive techniques for evaluating transplant success. Here, we
      obtained bone marrow from the femurs of six dogs and expanded BMSCs in tissue
      culture. Autologous BMSC-hydroxyapatite/tricalcium phosphate (HA/TCP) transplants
      were introduced into critical-sized calvarial defects and contralateral control
      skull defects received HA/TCP vehicle alone. At intervals ranging from 2 to 20
      months, transplants were biopsied or harvested for histological and mechanical
      analysis. Noninvasive studies, including quantitative computed tomography scans
      and ultrasound, were simultaneously obtained. In all animals, BMSC-containing
      transplants formed significantly more bone than their control counterparts. BMSC
      associated bone possessed mechanical properties similar to the adjacent normal
      bone, confirmed by both ultrasound and ex vivo analysis. Evaluation by
      quantitative computed tomography confirmed that the extent of bone formation
      demonstrated by histology could be discerned through noninvasive means. These
      results show that autologous cultured BMSC transplantation is a feasible therapy
      in clinical-sized bone defects and that such transplants can be assessed
      noninvasively, suggesting that this technique has potential for use in patients
      with certain bone defects.

PMID- 16436667
TI  - Monocytes/macrophages cooperate with progenitor cells during neovascularization
      and tissue repair: conversion of cell columns into fibrovascular bundles.
AB  - The potential of monocytes/macrophages (MC/Mph) to contribute to
      neovascularization has recently become a topic of intense scrutiny. Here, we
      characterized the behavior of MC/Mph in cellular infiltrates, with emphasis on
      their spatial organization and localization in newly formed microvessels. To this
      end, we studied MC/Mph migration and assembly in basic fibroblast growth factor
      supplemented Matrigel plugs placed in transgenic Tie2-beta-galactosidase mice for
      up to 4 weeks. In these plugs, along with Nile Red-positive adipocytes, we found
      MC/Mph distributed in cell cords, also containing various mature and progenitor
      tissue cells; and functional Tie2-positive or -negative microvessels embedded in
      bundles of fibrillar collagen surrounded by F4/80-positive MC/Mph. At earlier
      stages of infiltration, we found tubular destruction of the matrix (tunnels) and
      MC/Mph-lined capillary-like structures occasionally containing erythrocytes,
      indicating their propensity for endothelial trans-differentiation. We also
      analyzed in vitro the MCP-1-induced chemotactic migration of fluorescently
      labeled peritoneal MC/Mph incorporated in Matrigel-containing fluorescent
      protease substrates. Many of these MC/Mph produced MMP-12- and TIMP-1-dependent
      tunnels coupled with acquisition of a lumen. In conclusion, long-term
      implantation of Matrigel plugs qualifies as a novel experimental model of tissue
      regeneration, in which neovascularization intimately couples with fibrosis and
      organogenesis and in which cells of MC/Mph phenotype play a key structural role.

PMID- 16436669
TI  - Override of the osteoclast defect in osteopontin-deficient mice by metastatic
      tumor growth in the bone.
AB  - Osteopontin (OPN) is a major noncollagenous protein of bone that is frequently up
      regulated in tumors, where it enhances tumor growth. OPN-deficient mice are
      resistant to stimulated bone resorption, including that occurring after
      ovariectomy. Using a new syngeneic model of bone metastasis (r3T), we examined
      whether OPN-deficient mice are similarly resistant to bone loss resulting from
      osteolytic tumor growth. Transformed mammary epithelial cells, r3T, which express
      parathyroid hormone-related protein but not receptor activator of nuclear factor
      kappaB ligand, were injected via the intracardiac route into both wild-type and
      OPN-/- mice. We measured tumor burden in the bone by quantitative polymerase
      chain reaction assay and evaluated bone loss by X-ray and microCT. Unexpectedly,
      bone loss was similar in OPN-/- and wild-type mice bearing similar-sized tumors.
      Osteoclast number was comparable in both genotypes, and the expression of bone
      sialoprotein was similar in tumor-bearing bones of both genotypes, excluding two
      potential mechanisms of overriding the defect. Taken together, these results
      indicate that in the absence of OPN, the bone loss associated with tumor growth
      at the bone site proceeds rapidly despite the osteoclast defects documented in
      OPN-/- mice, suggesting that the mechanism of bone loss due to tumor growth
      differs from that occurring in other pathologies.

PMID- 16436670
TI  - RhoGTPases and p53 are involved in the morphological appearance and interferon
      alpha response of hairy cells.
AB  - Hairy cell leukemia is an uncommon B-cell lymphoproliferative disease of unknown
      etiology in which tumor cells display characteristic microfilamentous membrane
      projections. Another striking feature of the disease is its exquisite sensitivity
      to interferon (IFN)-alpha. So far, none of the known IFN-alpha regulatory
      properties have explained IFN-alpha responsiveness nor have they taken into
      account the morphological characteristics of hairy cells. IFN-alpha profoundly
      alters cytoskeletal organization of hairy cells and causes reversion of the hairy
      appearance into a rounded morphology. Because cytoskeletal rearrangements are
      controlled by the Rho family of GTPases, we investigated the GTPase activation
      status in hairy cells and their regulation by IFN-alpha. Using immunolocalization
      techniques and biochemical assays, we demonstrate that hairy cells display high
      levels of active Cdc42 and Rac1 and that IFN-alpha down-regulates these
      activities. In sharp contrast, RhoA activity was low in hairy cells but was
      increased by IFN-alpha treatment. Finally, IFN-alpha-mediated morphological
      changes also implicated a p53-induced response. These observations shed light on
      the mechanism of action of IFN-alpha in hairy cell leukemia and are of potential
      relevance for the therapeutical applications of this cytokine.

PMID- 16436671
TI  - Clusterin is a secreted marker for a hypoxia-inducible factor-independent
      function of the von Hippel-Lindau tumor suppressor protein.
AB  - Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene
      predispose people to renal cancer, hemangioblastomas, and pheochromocytomas in an
      allele-specific manner. The best documented function of the VHL gene product
      (pVHL) relates to its ability to polyubiquitinate, and hence target for
      destruction, the alpha subunits of the heterodimeric transcription factor hypoxia
      inducible factor (HIF). pVHL mutants linked to familial pheochromocyctoma (type
      2C VHL disease), in contrast to classical VHL disease, appear to be normal with
      respect to HIF regulation. Using a simple method for identifying proteins that
      are differentially secreted by isogenic cell line pairs, we confirmed that the
      HIF targets IGBP3 and PAI-1 are overproduced by pVHL-defective renal carcinoma
      cells. In addition, cells lacking wild-type pVHL, including cells producing type
      2C pVHL mutants, were defective with respect to expression and secretion of
      clusterin, which does not behave like a HIF target. Decreased clusterin secretion
      by pVHL-defective tumors was confirmed in vivo by immunohistochemistry.
      Therefore, clusterin is a secreted marker for a HIF-independent pVHL function
      that might be especially important in pheochromocytoma development.

PMID- 16436672
TI  - Rap1GAP inhibits tumor growth in oropharyngeal squamous cell carcinoma.
AB  - Rap1, a growth regulatory protein that is strongly expressed in human squamous
      cell carcinoma (SCC), is inactivated by rap1GAP. Recent evidence in normal rat
      cells suggests that rap1GAP regulates proliferation. The objective of the current
      study was to investigate whether rap1GAP functions as a tumor suppressor in SCC.
      Using a pull-down assay, active GTP-bound rap1 was up-regulated in SCC compared
      to normal or immortalized keratinocytes. Because both rap1A and rap1B isoforms of
      rap1 are expressed in SCC, the rap1GAP inactivation of both rap1 isoforms was
      verified using cells transfected with EGFP-rap1A or EGFP-rap1B or co-transfected
      with FLAG-tagged rap1GAP. The results demonstrate that expression of rap1GAP in
      oropharyngeal SCC down-regulated active rap1, ERK activation, and proliferation.
      Incubation of stably transfected SCC cells with nocodazole, an inhibitor of
      mitosis, caused a slower accumulation of rap1GAP-transfected cells in the G2
      phase, in comparison to the vector control, indicating that rap1GAP-transfected
      cells have slower progression through the cell cycle. This was supported by down
      regulation of cyclin D1, cdk4, and cdk6 in rap1GAP-transfected SCC cells.
      Furthermore, SCC cells transfected with rap1GAP produced significantly smaller
      tumors in nude mice as compared to controls (P < 0.01). These novel findings
      suggest that rap1GAP acts as a tumor suppressor protein in SCC.

PMID- 16436673
TI  - CSR1 suppresses tumor growth and metastasis of prostate cancer.
AB  - Prostate cancer is frequent among men over 45 years of age, but it generally only
      becomes lethal with metastasis. In this study, we identified a gene called
      cellular stress response 1 (CSR1) that was frequently down-regulated and
      methylated in prostate cancer samples. Survival analysis indicated that
      methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1
      protein expression, was associated with a high rate of prostate cancer
      metastasis. Forced expression of CSR1 in prostate cancer cell lines DU145 and PC3
      resulted in a two- to threefold decrease in colony formation and a 10-fold
      reduction in anchorage-independent growth. PC3 cells stably expressing CSR1 had
      an average threefold decrease in their ability to invade in vitro. Expression of
      CSR1 in PC3 cell xenografts produced a dramatic reduction (>8-fold) in tumor
      size, rate of invasion (0 versus 31%), and mortality (13 versus 100%). The
      present findings suggest that CSR1 is a potent tumor sup-pressor gene.

PMID- 16436674
TI  - Remodeling of the mammary microenvironment after lactation promotes breast tumor
      cell metastasis.
AB  - The mammary gland microenvironment during postlactational involution shares
      similarities with inflammation, including high matrix metalloproteinase activity,
      fibrillar collagen deposition, and release of bioactive fragments of fibronectin
      and laminin. Because inflammation can promote tumorigenesis, we evaluated whether
      the tissue microenvironment of the involuting gland is also promotional.
      Extracellular matrix was isolated from mammary glands of nulliparous rats or rats
      with mammary glands undergoing weaning-induced involution. Using these matrices
      as substratum, nulliparous matrix was found to promote ductal organization of
      normal mammary epithelial MCF-12A cells in three-dimensional culture and to
      suppress invasion of mammary tumor MDA-MB-231 cells in transwell filter assays.
      Conversely, involution matrix failed to support ductal development in normal
      cells and promoted invasiveness in tumor cells. To evaluate the effects of these
      matrices on metastasis in vivo, MDA-MB-231 cells, premixed with Matrigel,
      nulliparous matrix, or involution matrix, were injected into mammary fat pads of
      nude mice. Metastases to lung, liver, and kidney were increased in the involution
      matrix group, and correlated with a twofold increase in tumor vascular
      endothelial growth factor expression and increased angiogenesis. These data
      suggest that the mammary gland microenvironment becomes promotional for tumor
      cell dissemination during involution, thus providing a plausible mechanism to
      explain the high rate of metastases that occur with pregnancy-associated breast
      cancer.

PMID- 16436675
TI  - Myeloid cells in infantile hemangioma.
AB  - Little is known about the pathogenesis of infantile hemangiomas despite the fact
      that they are relatively common tumors. These benign neoplasms occur in as many
      as 1 in 10 births, and although rarely life threatening, hemangiomas can pose
      serious concerns to the cosmetic and psychosocial development of the afflicted
      child. Ulceration, scarring, and disfigurement are significant problems as are
      encroachment of the ear and eye, which can threaten hearing and vision. The
      precise mechanisms controlling the rapid growth observed in the first months of
      life and the spontaneous involution that follows throughout the course of years
      remain unknown. In this report we demonstrate the presence of large numbers of
      hematopoietic cells of the myeloid lineage in proliferating hemangiomas and
      propose a mechanism for the observed evolution of these lesions that is triggered
      by hypoxia and involves the participation of myeloid cells. We report the results
      of experiments using myeloid markers (CD83, CD32, CD14, CD15) that unexpectedly
      co-labeled hemangioma endothelial cells, providing new evidence that these cells
      are distinct from normal endothelium.

PMID- 16436676
TI  - Bone morphogenetic protein-2 induces proinflammatory endothelial phenotype.
AB  - The transforming growth factor-beta superfamily member bone morphogenetic protein
      2 (BMP-2) is up-regulated in atherosclerotic arteries; however, its effects on
      the endothelium are not well characterized. Using microdissected coronary
      arterial endothelial cells (CAECs) and cultured primary CAECs, we demonstrated
      endothelial mRNA expression of BMP-2 and BMP-4. The proinflammatory cytokine
      tumor necrosis factor-alpha and H2O2 significantly increased endothelial
      expression of BMP-2 but not BMP-4. In organ culture, BMP-2 substantially
      decreased relaxation of rat carotid arteries to acetylcholine and increased
      production of reactive oxygen species, events inhibited by pharmacologically
      blocking protein kinase C (PKC) or NAD(P)H oxidase. BMP-2 activated nuclear
      factor-kappaB in CAECs, and BMP-2 and BMP-4 substantially increased adhesion of
      monocytic THP-1 cells, which was reduced by pharmacologically inhibiting p42/44
      MAP kinase pathway (also by siRNA down-regulating ERK-1/2) or PKC. Incubation of
      rat carotid arteries with BMP-2 ex vivo also increased adhesion of mononuclear
      cells to the endothelium, requiring p42/44 MAP kinase and PKC. Western blotting
      showed that in CAECs and carotid arteries BMP-2 elicited phosphorylation of
      p42/44 MAP kinase, which was reduced by blocking MAP kinase kinase and PKC.
      Collectively, expression of BMP-2 is regulated by proinflammatory stimuli, and
      increased levels of BMP-2 induce endothelial dysfunction, oxidative stress, and
      endothelial activation. Thus, the proinflammatory effects of BMP-2 may play a
      role in vascular pathophysiology.

PMID- 16436677
TI  - Vascular endothelial growth factor localization in the adult.
AB  - Although vascular endothelial growth factor (VEGF) has been well studied in both
      developmental and pathological angiogenesis, its role in mature blood vessels is
      poorly understood. A growing body of observations, including the side effects of
      anti-VEGF therapies as well as the role of soluble VEGFR1 in preeclampsia, points
      to an important role for VEGF in maintenance of stable blood vessels. To better
      understand the potential function of VEGF in mature vessels, a survey of VEGF
      localization in adult mice was conducted. In adult VEGF-lacZ mice, VEGF was
      expressed in a cell-specific manner by cells overlying fenestrated and sinusoidal
      blood vessels, including podocytes, choroid plexus epithelium, and hepatocytes,
      as well as in tissues with high metabolic demands or with secretory functions,
      such as cardiac and skeletal myocytes, Leydig cells, prostatic epithelium, and
      salivary serous epithelium. VEGF was not detected in most endothelium but was
      specifically expressed by aortic endothelial cells where VEGFR2 was found to be
      phosphorylated, indicating an autocrine loop. Additionally, VEGFR2 was
      constitutively phosphorylated in the liver, lung, adipose, and kidney in vivo,
      providing evidence consistent with a role for VEGF in adult tissues. These
      observations support the concept that VEGF acts in the adult to stabilize mature
      vessels.

PMID- 16436678
TI  - Ionizing radiation accelerates the development of atherosclerotic lesions in ApoE
      /- mice and predisposes to an inflammatory plaque phenotype prone to hemorrhage.
AB  - After radiotherapy treatment, there is an increased incidence of localized
      atherosclerosis in patients with Hodgkin's disease, breast cancer, and head and
      neck cancer. Here, we established a mouse model to study the development and
      progression of radiation-induced atherosclerosis and to compare the phenotype of
      these lesions with age-related atherosclerosis. Atherosclerosis-prone ApoE-/-
      mice fed a regular chow diet received single radiation doses of 14 Gy or sham
      treatments (0 Gy) to the neck, including both carotid arteries. At 22, 28, and 34
      weeks after irradiation, blood samples were taken, and the arterial tree was
      removed for histological examination. Cholesterol levels in irradiated mice were
      not significantly different from age-matched controls, and markers of systemic
      inflammation (soluble intercellular adhesion molecule-1, soluble vascular cell
      adhesion molecule-1, and C-reactive protein) were not elevated. The lesions in
      irradiated arteries were macrophage rich, with a remarkable influx of
      inflammatory cells, predominantly granulocytes. Intraplaque hemorrhage and
      erythrocyte-containing macrophages were seen only in lesions of irradiated
      arteries. Based on these data, we propose that irradiation accelerates the
      development of macrophage-rich, inflammatory atherosclerotic lesions prone to
      intraplaque hemorrhage.

PMID- 16436679
TI  - Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating
      mesenchymal precursors of a monocyte/macrophage lineage.
AB  - Vascular remodeling in chronic hypoxic pulmonary hypertension includes marked
      fibroproliferative changes in the pulmonary artery (PA) adventitia. Although
      resident PA fibroblasts have long been considered the primary contributors to
      these processes, we tested the hypothesis that hypoxia-induced pulmonary vascular
      remodeling requires recruitment of circulating mesenchymal precursors of a
      monocyte/macrophage lineage, termed fibrocytes. Using two neonatal animal models
      (rats and calves) of chronic hypoxic pulmonary hypertension, we demonstrated a
      dramatic perivascular accumulation of mononuclear cells of a monocyte/macrophage
      lineage (expressing CD45, CD11b, CD14, CD68, ED1, ED2). Many of these cells
      produced type I collagen, expressed alpha-smooth muscle actin, and proliferated,
      thus exhibiting mesenchymal cell characteristics attributed to fibrocytes. The
      blood-borne origin of these cells was confirmed in experiments wherein
      circulating monocytes/macrophages of chronically hypoxic rats were in vivo
      labeled with DiI fluorochrome via liposome delivery and subsequently identified
      in the remodeled pulmonary, but not systemic, arterial adventitia. The DiI
      labeled cells that appeared in the vessel wall expressed monocyte/macrophage
      markers and procollagen. Selective depletion of this monocytic cell population,
      using either clodronate-liposomes or gadolinium chloride, prevented pulmonary
      adventitial remodeling (ie, production of collagen, fibronectin, and tenascin-C
      and accumulation of myofibroblasts). We conclude that circulating mesenchymal
      precursors of a monocyte/macrophage lineage, including fibrocytes, are essential
      contributors to hypoxia-induced pulmonary vascular remodeling.

PMID- 16436681
TI  - Localization of cysteine protease, cathepsin S, to the surface of vascular smooth
      muscle cells by association with integrin alphanubeta3.
AB  - Smooth muscle cell (SMC) migration from the tunica media to the intima, a key
      event in neointimal formation, requires proteolytic degradation of elastin-rich
      extracellular matrix barriers. Although cathepsin S (Cat S) is overexpressed in
      atherosclerotic and neointimal lesions, its exact role in SMC behavior remains
      primarily unresolved. We examined the involvement of Cat S on SMC migration
      through an extracellular matrix barrier and its localization in SMCs. A selective
      Cat S inhibitor and the endogenous inhibitor cystatin C significantly attenuated
      SMC invasion across elastin gel. Western blotting and cell surface biotinylation
      analysis demonstrated localization of the 28-kd active form of Cat S on the SMC
      surface, consistent with its role in the proteolysis of subcellular matrices.
      Treatment with interferon-gamma or interleukin-beta1 significantly augmented the
      ability of SMC membranes to degrade elastin along with a significant increase in
      the level of active Cat S compared with controls. Immunofluorescence and confocal
      microscopy showed a punctuated pattern of Cat S clusters at the periphery of
      SMCs; further studies demonstrated partial co-localization of Cat S and integrin
      alphanubeta3 at the cell surfaces. These findings demonstrate that active Cat S
      co-localizes with integrin alphanubeta3 as a receptor on the SMC surface, playing
      an important role in the invasive behavior of SMCs.

PMID- 16436680
TI  - Plasmin modulates vascular endothelial growth factor-A-mediated angiogenesis
      during wound repair.
AB  - Plasmin-catalyzed cleavage of the vascular endothelial growth factor (VEGF)-A
      isoform VEGF165 results in loss of its carboxyl-terminal heparin-binding domain
      and significant loss in its bioactivity. Little is known about the in vivo
      significance of this process. To investigate the biological relevance of the
      protease sensitivity of VEGF165 in wound healing we assessed the activity of a
      VEGF165 mutant resistant to plasmin proteolysis (VEGF165(A111P)) in a genetic
      mouse model of impaired wound healing (db/db mouse). In the present study we
      demonstrate that in this mouse model plasmin activity is increased at the wound
      site. The stability of the mutant VEGF165 was substantially increased in wound
      tissue lysates in comparison to wild-type VEGF165, thus indicating a prolonged
      activity of the plasmin-resistant VEGF165 mutant. The db/db delayed healing
      phenotype could be reversed by topical application of wild-type VEGF165 or
      VEGF165(A111P). However, resistance of VEGF165 to plasmin cleavage resulted in
      the increased stability of vascular structures during the late phase of healing
      due to increased recruitment of perivascular cells and delayed and reduced
      endothelial cell apoptosis. Our data provide the first indication that plasmin
      catalyzed cleavage regulates VEGF165-mediated angiogenesis in vivo. Inactivation
      of the plasmin cleavage site Arg110/Ala111 may preserve the biological function
      of VEGF165 in therapeutic angiogenesis under conditions in which proteases are
      highly active, such as wound repair and inflammation.

PMID- 16436682
TI  - Vascular endothelial growth factor antagonist modulates leukocyte trafficking and
      protects mouse livers against ischemia/reperfusion injury.
AB  - Although hypoxia stimulates the expression of vascular endothelial growth factor
      (VEGF), little is known of the role or mechanism by which VEGF functions after
      ischemia and reperfusion (I/R) injury. In this report, we first evaluated the
      expression of VEGF in a mouse model of liver warm ischemia. We found that the
      expression of VEGF increased after ischemia but peaked between 2 and 6 hours
      after reperfusion. Mice were treated with a neutralizing anti-mouse VEGF
      antiserum (anti-VEGF) or control serum daily from day -1 (1 day before the
      initiation of ischemia). Treatment with anti-VEGF significantly reduced serum
      glutaminic pyruvic transaminase levels and reduced histological evidence of
      hepatocellular damage compared with controls. Anti-VEGF also markedly decreased T
      cell, macrophage, and neutrophil accumulation within livers and reduced the
      frequency of intrahepatic apoptotic terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling-positive cells. Moreover, there was a reduction
      in the expression of pro-inflammatory cytokines (tumor necrosis factor-alpha and
      interferon-gamma), chemokines (interferon-inducible protein-10 and monocyte
      chemoattractant protein-1) and adhesion molecules (E-selectin) in parallel with
      enhanced expression of anti-apoptotic genes (Bcl-2/Bcl-xl and heme oxygenase-1)
      in anti-VEGF-treated animals. In conclusion, hypoxia-inducible VEGF expression by
      hepatocytes modulates leukocyte trafficking and leukocyte-induced injury in a
      mouse liver model of warm I/R injury, demonstrating the importance of endogenous
      VEGF production in the pathophysiology of hepatic I/R injury.

PMID- 16436683
TI  - Expression of Pax2 in human renal tumor-derived endothelial cells sustains
      apoptosis resistance and angiogenesis.
AB  - The transcription factor Pax2 is known to play a key role during renal
      development and to act as an oncogene favoring renal tumor growth. We recently
      showed that endothelial cells derived from human renal carcinomas display
      abnormal characteristics of survival and angiogenic properties. In the present
      study we found that renal tumor-derived endothelial cells, but not normal
      endothelial cells, expressed Pax2 protein and mRNA. To down-regulate Pax2
      expression, we transfected tumor-derived endothelial cells with an anti-sense
      PAX2 vector whereas we transfected normal human microvascular endothelial cells
      with a sense PAX2 vector to induce Pax2 expression. The inhibition of Pax2
      expression in tumor-derived endothelial cells induced an increase in tumor
      suppressor PTEN expression and a decrease in Akt phosphorylation. In addition,
      decreased apoptosis resistance, adhesion, invasion, and in vitro and in vivo
      angiogenesis were observed. Conversely, Pax2 induction in normal endothelial
      cells conferred to these cells a proinvasive, proangiogenic phenotype similar to
      that of tumor-derived endothelial cells. These results indicate that Pax2 is
      involved in renal tumor angiogenesis and its expression may antagonize that of
      the PTEN tumor suppressor gene, affecting the Akt-survival pathway and promoting
      angiogenesis.

PMID- 16436684
TI  - Rapid face-selective adaptation of an early extrastriate component in MEG.
AB  - Adaptation paradigms are becoming increasingly popular for characterizing visual
      areas in neuroimaging, but the relation of these results to perception is
      unclear. Neurophysiological studies have generally reported effects of stimulus
      repetition starting at 250-300 ms after stimulus onset, well beyond the latencies
      of components associated with perception (100-200 ms). Here we demonstrate
      adaptation for earlier evoked components when 2 stimuli (S1 and S2) are presented
      in close succession. Using magnetoencephalography, we examined the M170, a "face
      selective" response at 170 ms after stimulus onset that shows a larger response
      to faces than to other stimuli. Adaptation of the M170 occurred only when stimuli
      were presented with relatively short stimulus onset asynchronies (< 800 ms) and
      was larger for faces preceded by faces than by houses. This face-selective
      adaptation is not merely low-level habituation to physical stimulus attributes,
      as photographic, line-drawing, and 2-tone face images produced similar levels of
      adaptation. Nor does it depend on the amplitude of the S1 response: adaptation
      remained greater for faces than houses even when the amplitude of the S1 face
      response was reduced by visual noise. These results indicate that rapid
      adaptation of early, short-latency responses not only exists but also can be
      category selective.

PMID- 16436685
TI  - Neural correlates of rule-based and information-integration visual category
      learning.
AB  - An emerging theory of the neurobiology of category learning postulates that there
      are separate neural systems supporting the learning of categories based on
      verbalizeable rules (RB) or through implicit information integration (II). The
      medial temporal lobe (MTL) is thought to play a crucial role in successful RB
      categorization, whereas the posterior regions of the caudate are hypothesized to
      support II categorization. Functional neuroimaging was used to assess activity in
      these systems during category-learning tasks with category structures designed to
      afford either RB or II learning. Successful RB categorization was associated with
      relatively increased activity in the anterior MTL. Successful II categorization
      was associated with increased activity in the caudate body. The dissociation
      observed with neuroimaging is consistent with the roles of these systems in
      memory and dissociations reported in patient populations. Convergent evidence
      from these approaches consistently reinforces the idea of multiple neural systems
      supporting category learning.

PMID- 16436686
TI  - Fractionating attentional control using event-related fMRI.
AB  - Despite numerous functional neuroimaging and lesion studies of human executive
      function, the precise neuroanatomical correlates of specific components of
      attentional control remain controversial. Using a novel approach that focused
      upon volunteer behavior rather than experimental manipulations, specific
      components of attentional shifting were fractionated, and their neural correlates
      differentiated using event-related fMRI. The results demonstrate that the
      ventrolateral prefrontal cortex is involved in switching attention "between"
      stimulus dimensions, whereas the posterior parietal cortex mediates changes in
      stimulus-response mapping. Furthermore, reversals based on negative feedback
      activated the lateral orbitofrontal cortex, whereas positive feedback modulated
      activity in the medial orbital frontal cortex. Finally, the dorsolateral
      prefrontal cortex was active throughout solution search. These findings support
      the hypothesis that lateral prefrontal, orbital, and parietal areas form a
      supervisory network that controls the focus of attention and suggests that these
      regions can be fractionated in terms of their specific contributions.

PMID- 16436687
TI  - Olfactory deficits in patients affected by minimal hepatic encephalopathy: a
      pilot study.
AB  - Minimal hepatic encephalopathy (MHE) is the earliest stage of hepatic
      encephalopathy and is associated with changes in cognitive functions, in
      electrophysiological parameters, and in cerebral neurochemical/neurotransmitter
      homeostasis. MHE can be observed in patients with cirrhosis who have no clinical
      evidence of hepatic encephalopathy (HE). At present, no data are available on a
      possible olfactory dysfunction in such a syndrome, although the pathophysiology
      of HE may alter olfactory functions since some of the neurotransmitters impaired
      in the syndrome are involved in the transmission of olfactory information. In the
      present paper, we performed a preliminary study aimed at detecting whether
      identification and recognition odor memory is altered in patients with MHE.
      Twelve patients diagnosed as MHE on the basis of their scores at the
      portosystemic encephalopathy (PSE)-syndrome test battery, and 12 age-matched
      controls were studied. Consistent with the hypothesis, patients performed
      significantly worse than controls for both odor identification and recognition
      tasks. In addition, a significant correlation between the two olfactory tests and
      the PSE-syndrome test score was found. This pattern supports the notion that
      olfactory alterations related to cognitive dysfunction in patients with MHE may
      be linked to the pathophysiology of HE.

PMID- 16436688
TI  - Site fidelity and homing in tropical coral reef cardinalfish: are they using
      olfactory cues?
AB  - A number of tropical coral reef fish hold station and display restricted home
      ranges. If artificially displaced, they will return to their home site. We
      questioned if marine fish are using the same mechanisms for home site detection
      as many freshwater fish, that is, by olfactory sensing of chemical signals
      deposited on the substrate by conspecific fish. Behavioral experiments were
      conducted on Lizard Island Research Station, Queensland, Australia, in 2001 and
      2002. Five-lined cardinalfish (Cheilodipterus quinquelineatus) were tested in
      groups with split-branded cardinalfish (Apogon compressus) as a reference species
      and individually against Apogon leptacanthus as well as conspecifics of another
      reef site. The group tests showed that both species preferred artificial reef
      sites that had previously been occupied by conspecifics. Individual C.
      quinquelineatus preferred scent of conspecifics from their own reef site to that
      from another site. They also preferred the scent released by artificial reefs
      previously occupied by conspecifics of their reef site to that of similar reefs
      previously occupied by conspecifics of another reef site. No discrimination
      between species from the same reef site was obtained in experiments with
      individual fish. Our data suggest that cardinalfish are keeping station and are
      homing by use of conspecific olfactory signals.

PMID- 16436689
TI  - Trpm5 null mice respond to bitter, sweet, and umami compounds.
AB  - Trpm5 is a calcium-activated cation channel expressed selectively in taste
      receptor cells. A previous study reported that mice with an internal deletion of
      Trpm5, lacking exons 15-19 encoding transmembrane segments 1-5, showed no taste
      mediated responses to bitter, sweet, and umami compounds. We independently
      generated knockout mice null for Trpm5 protein expression due to deletion of
      Trpm5's promoter region and exons 1-4 (including the translation start site). We
      examined the taste-mediated responses of Trpm5 null mice and wild-type (WT) mice
      using three procedures: gustatory nerve recording [chorda tympani (CT) and
      glossopharyngeal (NG) nerves], initial lick responses, and 24-h two-bottle
      preference tests. With bitter compounds, the Trpm5 null mice showed reduced, but
      not abolished, avoidance (as indicated by licking responses and preference ratios
      higher than those of WT), a normal CT response, and a greatly diminished NG
      response. With sweet compounds, Trpm5 null mice showed no licking response, a
      diminished preference ratio, and absent or greatly reduced nerve responses. With
      umami compounds, Trpm5 null mice showed no licking response, a diminished
      preference ratio, a normal NG response, and a greatly diminished CT response. Our
      results demonstrate that the consequences of eliminating Trmp5 expression vary
      depending upon the taste quality and the lingual taste field examined. Thus,
      while Trpm5 is an important factor in many taste responses, its absence does not
      eliminate all taste responses. We conclude that Trpm5-dependent and Trpm5
      independent pathways underlie bitter, sweet, and umami tastes.

PMID- 16436690
TI  - Low levels of pyrazinamide and ethambutol in children with tuberculosis and
      impact of age, nutritional status, and human immunodeficiency virus infection.
AB  - Recent pharmacokinetic studies that included children found that serum drug
      levels were low compared to those of adults for whom the same dosages were used.
      This study aimed to characterize the pharmacokinetics of pyrazinamide and
      ethambutol in Malawian children and to examine the impact of age, nutritional
      status, and human immunodeficiency virus (HIV) infection. We conducted a
      pharmacokinetic study of children treated for tuberculosis with thrice-weekly
      pyrazinamide (n = 27; mean age, 5.7 years) and of a separate group of children
      treated with thrice-weekly ethambutol (n = 18; mean age, 5.5 years) as portions
      of tablets according to national guidelines. Malnutrition and HIV infection were
      common in both groups. Blood samples were taken just prior to oral administration
      of the first dose, and subsequent samples were taken at intervals of 2, 3, 4, 7,
      24, and 48 h after drug administration. Serum drug levels were low in all
      children for both drugs; in almost all cases, the maximum concentration of the
      drug in serum (Cmax) failed to reach the MIC for Mycobacterium tuberculosis. The
      Cmax of pyrazinamide was significantly lower in younger children (<5 years) than
      in older children. The Cmax of pyrazinamide was also lower for HIV-infected
      children and children with severe malnutrition, but these differences did not
      reach statistical significance. No differences were found for ethambutol in
      relation to age, HIV infection, or malnutrition, but the Cmax was <2 mg/liter in
      all cases. Studies of pharmacokinetic parameters and clinical outcomes obtained
      by using higher dosages of drugs for treatment of childhood tuberculosis are
      needed, and recommended dosages may need to be increased.

PMID- 16436691
TI  - Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and
      is efficacious in a mouse model of cryptococcosis.
AB  - The alkyl phosphocholine drug miltefosine is structurally similar to natural
      substrates of the fungal virulence determinant phospholipase B1 (PLB1), which is
      a potential drug target. We determined the MICs of miltefosine against key fungal
      pathogens, correlated antifungal activity with inhibition of the PLB1 activities
      (PLB, lysophospholipase [LPL], and lysophospholipase-transacylase [LPTA]), and
      investigated its efficacy in a mouse model of disseminated cryptococcosis.
      Miltefosine inhibited secreted cryptococcal LPTA activity by 35% at the
      subhemolytic concentration of 25 microM (10.2 microg/ml) and was inactive against
      mammalian pancreatic phospholipase A2 (PLA2). At 250 microM, cytosolic PLB, LPL,
      and LPTA activities were inhibited by 25%, 51%, and 77%, respectively. The MICs
      at which 90% of isolates were inhibited (MIC90s) against Candida albicans,
      Candida glabrata, Candida krusei, Cryptococcus neoformans, Cryptococcus gattii,
      Aspergillus fumigatus, Fusarium solani, Scedosporium prolificans, and
      Scedosporium apiospermum were 2 to 4 microg/ml. The MICs of miltefosine against
      Candida tropicalis (n = 8) were 2 to 4 microg/ml, those against Aspergillus
      terreus and Candida parapsilosis were 8 microg/ml (MIC90), and those against
      Aspergillus flavus (n = 8) were 2 to 16 microg/ml. Miltefosine was fungicidal for
      C. neoformans, with rates of killing of 2 log units within 4 h at 7.0 microM (2.8
      microg/ml). Miltefosine given orally to mice on days 1 to 5 after intravenous
      infection with C. neoformans delayed the development of illness and mortality and
      significantly reduced the brain cryptococcal burden. We conclude that miltefosine
      has broad-spectrum antifungal activity and is active in vivo in a mouse model of
      disseminated cryptococcosis. The relatively small inhibitory effect on PLB1
      enzyme activities at concentrations exceeding the MIC by 2 to 20 times suggests
      that PLB1 inhibition is not the only mechanism of the antifungal effect.

PMID- 16436692
TI  - Effect of amphotericin B and micafungin combination on survival, histopathology,
      and fungal burden in experimental aspergillosis in the p47phox-/- mouse model of
      chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase
      characterized by recurrent life-threatening bacterial and fungal infections. We
      characterized the effects of single and combination antifungal therapy on
      survival, histopathology, and laboratory markers of fungal burden in experimental
      aspergillosis in the p47phox-/- knockout mouse model of CGD. CGD mice were highly
      susceptible to intratracheal Aspergillus fumigatus challenge, whereas wild-type
      mice were resistant. CGD mice were challenged intratracheally with a lethal
      inoculum (1.25 x 10(4) CFU/mouse) of A. fumigatus and received one of the
      following regimens daily from day 0 to 4 after challenge (n = 19 to 20 per
      treatment group): (i) vehicle, (ii) amphotericin B (intraperitoneal; 1 mg/kg of
      body weight), (iii) micafungin (intravenous; 10 mg/kg), or (iv) amphotericin B
      plus micafungin. The rank order of therapeutic efficacy based on prolonged
      survival, from highest to lowest, was as follows: amphotericin B plus micafungin,
      amphotericin B alone, micafungin alone, and the vehicle. Lung histology showed
      pyogranulomatous lesions and invasive hyphae, but without hyphal angioinvasion or
      coagulative necrosis. Treatment with micafungin alone or combined with
      amphotericin B produced swelling of invasive hyphae that was not present in mice
      treated with the vehicle or amphotericin B alone. Assessment of lung fungal
      burden by quantitative PCR showed no significant difference between treatment
      groups. Serum galactomannan levels were at background despite documentation of
      invasive aspergillosis by histology. Our findings showed the superior efficacy of
      the amphotericin B and micafungin combination compared to either agent alone
      after A. fumigatus challenge and also demonstrated unique features of CGD mice as
      a model for experimental aspergillosis.

PMID- 16436693
TI  - Novel mechanism of antibiotic resistance originating in vancomycin-intermediate
      Staphylococcus aureus.
AB  - As an aggressive pathogen, Staphylococcus aureus poses a significant public
      health threat and is becoming increasingly resistant to currently available
      antibiotics, including vancomycin, the drug of last resort for gram-positive
      bacterial infections. S. aureus with intermediate levels of resistance to
      vancomycin (vancomycin-intermediate S. aureus [VISA]) was first identified in
      1996. The resistance mechanism of VISA, however, has not yet been clarified. We
      have previously shown that cell wall thickening is a common feature of VISA, and
      we have proposed that a thickened cell wall is a phenotypic determinant for
      vancomycin resistance in VISA (L. Cui, X. Ma, K. Sato, et al., J. Clin.
      Microbiol. 41:5-14, 2003). Here we show the occurrence of an anomalous diffusion
      of vancomycin through the VISA cell wall, which is caused by clogging of the cell
      wall with vancomycin itself. A series of experiments demonstrates that the
      thickened cell wall of VISA could protect ongoing peptidoglycan biosynthesis in
      the cytoplasmic membrane from vancomycin inhibition, allowing the cells to
      continue producing nascent cell wall peptidoglycan and thus making the cells
      resistant to vancomycin. We conclude that the cooperative effect of the clogging
      and cell wall thickening enables VISA to prevent vancomycin from reaching its
      true target in the cytoplasmic membrane, exhibiting a new class of antibiotic
      resistance in gram-positive pathogens.

PMID- 16436694
TI  - Rifalazil pretreatment of mammalian cell cultures prevents subsequent Chlamydia
      infection.
AB  - Chlamydia species are widely disseminated obligate intracellular pathogens that
      primarily cause urogenital, ocular, and respiratory infections. In these studies,
      we show that exposing mammalian cells to antibacterial agents prior to Chlamydia
      inoculation protects the host cells against subsequent challenge by chlamydiae
      (the protective effect [PE]). Rifalazil exhibited a considerably stronger PE than
      did azithromycin, rifampin, doxycycline, and ofloxacin. Specifically, 0.002
      microg/ml rifalazil incubated for 1 day with a monolayer of McCoy cells was
      sufficient to protect against a challenge 2 days later with Chlamydia trachomatis
      serovar D (UW-3). The PE was observed with five different mammalian cell lines
      and with a variety of C. trachomatis and Chlamydia pneumoniae isolates. The
      duration of the PE was 6 to 12 days for rifalazil (depending on the cell line), a
      maximum of 3 days for azithromycin, and less than a day for the other drugs
      tested. For rifalazil, the PE was shown to be mediated by inhibition of the
      chlamydial RNA polymerase since mutants with altered RNA polymerases had
      correspondingly altered PEs. These results suggest that rifalazil may be unique
      in its ability to prevent infection with obligate intracellular pathogens for a
      considerable time after treatment. This characteristic may be of particular
      public health value in reducing reinfection with chlamydiae.

PMID- 16436696
TI  - Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: role in sterol
      biosynthesis and antifungal drug susceptibility.
AB  - Two erg3 genes encoding C-5 sterol desaturase enzymes (Erg3A and Erg3B) in
      Aspergillus fumigatus were characterized with respect to their nucleotide
      sequences and null mutant phenotypes. Targeted disruption of the erg3A and erg3B
      genes and a double gene knockout, erg3A- erg3B-, showed that they are not
      essential for A. fumigatus viability. Mutant phenotypes clearly showed that Erg3B
      is a C-5 sterol desaturase, but no apparent role for Erg3A in A. fumigatus
      ergosterol biosynthesis was found. Susceptibility to amphotericin B,
      itraconazole, fluconazole, voriconazole, and ketoconazole was not altered in
      isolates in which erg3A and erg3B were knocked out alone and in combination.

PMID- 16436695
TI  - Mutations conferring aminoglycoside and spectinomycin resistance in Borrelia
      burgdorferi.
AB  - We have isolated and characterized in vitro mutants of the Lyme disease agent
      Borrelia burgdorferi that are resistant to spectinomycin, kanamycin, gentamicin,
      or streptomycin, antibiotics that target the small subunit of the ribosome. 16S
      rRNA mutations A1185G and C1186U, homologous to Escherichia coli nucleotides
      A1191 and C1192, conferred >2,200-fold and 1,300-fold resistance to
      spectinomycin, respectively. A 16S rRNA A1402G mutation, homologous to E. coli
      A1408, conferred >90-fold resistance to kanamycin and >240-fold resistance to
      gentamicin. Two mutations were identified in the gene for ribosomal protein S12,
      at a site homologous to E. coli residue Lys-87, in mutants selected in
      streptomycin. Substitutions at codon 88, K88R and K88E, conferred 7-fold
      resistance and 10-fold resistance, respectively, to streptomycin on B.
      burgdorferi. The 16S rRNA A1185G and C1186U mutations, associated with
      spectinomycin resistance, appeared in a population of B. burgdorferi parental
      strain B31 at a high frequency of 6 x 10(-6). These spectinomycin-resistant
      mutants successfully competed with the wild-type strain during 100 generations of
      coculture in vitro. The aminoglycoside-resistant mutants appeared at a frequency
      of 3 x 10(-9) to 1 x10(-7) in a population and were unable to compete with wild
      type strain B31 after 100 generations. This is the first description of mutations
      in the B. burgdorferi ribosome that confer resistance to antibiotics. These
      results have implications for the evolution of antibiotic resistance, because the
      16S rRNA mutations conferring spectinomycin resistance have no significant
      fitness cost in vitro, and for the development of new selectable markers.

PMID- 16436697
TI  - The two-component regulatory system mtrAB is required for morphotypic multidrug
      resistance in Mycobacterium avium.
AB  - Clinical isolates of the opportunistic pathogen Mycobacterium avium complex (MAC)
      undergo a reversible switch between red and white colony morphotypes on agar
      plates containing the lipoprotein stain Congo red. Compared to their isogenic red
      counterparts, white morphotypic variants are more virulent and more resistant to
      multiple antibiotics. This report shows that the two-component regulatory system
      mtrAB is required for the red-to-white switch as well as for other morphotypic
      switches of MAC. A mutant with a transposon insertion in the histidine protein
      kinase gene mtrB was isolated from a morphotypically white parent clone. The
      mutant resembled a naturally occurring red morphotypic variant in that it stained
      with Congo red, was sensitive to multiple antibiotics, and was permeable by a
      fluorescent DNA stain. However, it differed from a red variant in that it could
      not switch to the white or transparent morphotype, and it could not survive
      intracellularly within macrophage-like cells. Transcomplementation with a cloned
      wild-type mtrB gene restored to the mutant the ability to form impermeable, drug
      resistant white and transparent variants. Quantitative reverse transcriptase PCR
      showed that mtrB was required for the normal expression of cell surface Mce
      proteins, some of which are up-regulated in the red-to-white switch. The results
      indicate that mtrAB functions in regulating the composition and permeability of
      mycobacterial cell walls and plays a role in the reversible colony type switches
      of MAC.

PMID- 16436698
TI  - Pharmacodynamic activity of amphotericin B deoxycholate is associated with peak
      plasma concentrations in a neutropenic murine model of invasive pulmonary
      aspergillosis.
AB  - We conducted a dose fractionation study of neutropenic, corticosteroid
      immunosuppressed mice to characterize the pharmacodynamic/pharmacokinetic (PK/PD)
      parameter most closely associated with amphotericin B (AMB) efficacy in the
      treatment of invasive pulmonary aspergillosis. Pharmacokinetic parameter
      estimates were determined by a nonparametric population pharmacokinetic analysis
      of plasma drug concentrations following single intraperitoneal doses (0.25, 1.0,
      and 3.0 mg/kg of body weight) of amphotericin B deoxycholate. Three dosage groups
      (0.5, 0.75, and 1.0 mg/kg) fractionated into three dosing intervals (every 8 h
      [q8h], q24h, or q72h) were tested to discriminate between the PK/PD parameters
      (the ratio of maximum concentration of drug in serum [Cmax]/MIC, the ratio of
      area under the concentration-time curve/MIC, and percentage of time above MIC)
      most closely associated with AMB efficacy over a range of clinically achievable
      exposures in humans. The efficacy of each regimen was determined by quantitative
      PCR and survival. Reductions in pulmonary fungal burden and improvements in
      survival were maximized at the highest peak plasma concentrations in each of the
      dosage groups. Reductions in pulmonary fungal burden and increased survival were
      most closely associated with Cmax/MIC, with maximal activity occurring as the
      Cmax/MIC approached 2.4. In our model, Cmax/MIC is the PK/PD parameter most
      closely associated with efficacy in the treatment of invasive pulmonary
      aspergillosis. These data predict that less frequently administered, higher
      dosages of AMB would optimize efficacy.

PMID- 16436699
TI  - Novel compounds active against Leishmania major.
AB  - Leishmania major is an important trypanosomatid pathogen that causes
      leishmaniasis, which is a serious disease in much of the Old World. Current
      treatments include a small number of antimony compounds that, while somewhat
      effective, are limited by serious side effects. We have screened a small portion
      of a unique chemical library and have found at least three novel compounds that
      are effective against L. tarentolae and L. major in vitro and in a murine
      macrophage model of L. major infection. These compounds were effective in both
      assays at doses significantly lower than those of sodium stibogluconate
      (Pentostam) and represent possible candidates for drug development.

PMID- 16436700
TI  - Malaria parasites can develop stable resistance to artemisinin but lack mutations
      in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+
      ATPase), tctp, mdr1, and cg10.
AB  - Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine
      pyrimethamine is a major problem in malaria control. Artemisinin (ART)
      derivatives, particularly in combination with other drugs, are thus increasingly
      used to treat malaria, reducing the probability that parasites resistant to the
      components will emerge. Although stable resistance to artemisinin has yet to be
      reported from laboratory or field studies, its emergence would be disastrous
      because of the lack of alternative treatments. Here, we report for the first
      time, to our knowledge, genetically stable and transmissible ART and artesunate
      (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria
      parasite Plosmodium chabaudi chabaudi, grown in the presence of increasing
      concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to
      ART and ATN, respectively. Resistance remained stable after cloning, freeze
      thawing, after passage in the absence of drug, and transmission through
      mosquitoes. The nucleotide sequences of the possible genetic modulators of ART
      resistance (mdr1, cg10, tctp, and atp6) of sensitive and resistant parasites were
      compared. No mutations in these genes were identified. In addition we
      investigated whether changes in the copy number of these genes could account for
      resistance but found that resistant parasites retained the same number of copies
      as their sensitive progenitors. We believe that this is the first report of a
      malaria parasite with genetically stable and transmissible resistance to
      artemisinin or its derivatives.

PMID- 16436701
TI  - Antibacterial properties of dermaseptin S4 derivatives under extreme incubation
      conditions.
AB  - Antibacterial properties of the frog-derived peptide dermaseptin S4 and a series
      of synthetic derivatives against the food pathogen Escherichia coli O157:H7 were
      investigated under extreme incubation conditions. The 28-mer analog K4K20S4 (P28)
      displayed an MIC of 8 microM and rapid bactericidal kinetics under standard
      culture conditions. Potent bactericidal properties were maintained at high salt
      concentrations, under acidic or basic conditions, and at extreme temperatures.
      The N-terminal 14-mer sequence (P14) displayed higher potency (MIC, 4 microM) but
      only within a narrow range of incubation conditions, pointing to the importance
      of the C-terminal domain of P28. The potency range was reextended upon
      conjugation of aminododecanoic acid to P14. The resulting lipopeptide was even
      more potent (MIC, 2 microM) and affected bacterial viability under most of the
      conditions tested, including in commercial apple juice. The mechanistic
      implications of peptides' hydrophobicity, charge, structure, and binding to an
      idealized membrane were probed and are discussed here. Collectively, the data
      indicate interest in simple peptide-based compounds for design of antimicrobials
      that affect pathogens under a variable range of incubation conditions.

PMID- 16436702
TI  - Bloodstream infections caused by extended-spectrum-beta-lactamase-producing
      Klebsiella pneumoniae: risk factors, molecular epidemiology, and clinical
      outcome.
AB  - Bloodstream infections caused by extended-spectrum-beta-lactamase (ESBL)
      producing Klebsiella pneumoniae isolates are a major concern for clinicians,
      since they markedly increase the rates of treatment failure and death. One
      hundred forty-seven patients with K. pneumoniae bloodstream infections were
      identified over a 5-year period (January 1999 to December 2003). The production
      of ESBLs in bloodstream isolates was evaluated by molecular methods. A
      retrospective case-case-control study was conducted to identify risk factors for
      the isolation of ESBL-producing K. pneumoniae or non-ESBL-producing K. pneumoniae
      isolates in blood cultures. Forty-eight cases infected with ESBL-producing K.
      pneumoniae isolates and 99 cases infected with non-ESBL-producing K. pneumoniae
      isolates were compared to controls. Risk factors for isolation of ESBL-producing
      K. pneumoniae isolates were exposure to antibiotic therapy (odds ratio [OR],
      11.81; 95% confidence interval [CI], 2.72 to 51.08), age (OR, 1.14; 95% CI, 1.08
      to 1.21), and length of hospitalization (OR, 1.10; 95% CI, 1.04 to 1.16).
      Independent determinants for isolation of non-ESBL-producing K. pneumoniae were
      previous urinary tract infection (OR, 8.50; 95% CI, 3.69 to 19.54) and length of
      hospitalization (OR, 1.07; 95% CI, 1.04 to 1.10). When the initial response was
      assessed at 72 h after antimicrobial therapy, the treatment failure rate for the
      ESBL-producing K. pneumoniae-infected group was almost twice as high as that of
      the non-ESBL-producing K. pneumoniae-infected group (31% versus 17%; OR, 2.19;
      95% CI, 0.98 to 4.89). The 21-day mortality rate for all patients was 37% (54 of
      147); it was 52% (25 of 48) for patients with ESBL-producing K. pneumoniae
      bloodstream infections and 29% (29 of 99) for patients with non-ESBL-producing K.
      pneumoniae bloodstream infections (OR, 2.62; 95% CI, 1.28 to 5.35). In summary,
      this investigation identifies epidemiological characteristics that distinguish
      ESBL-producing K. pneumoniae infections from non-ESBL-producing K. pneumoniae
      ESBL bloodstream infections.

PMID- 16436703
TI  - Diagnostic PCR analysis of the occurrence of methicillin and tetracycline
      resistance genes among Staphylococcus aureus isolates from phase 3 clinical
      trials of tigecycline for complicated skin and skin structure infections.
AB  - Diagnostic PCR assays were developed to track common genetic determinants of
      oxacillin resistance as well as resistance to classical tetracyclines in
      Staphylococcus aureus isolates from the recently completed worldwide phase 3
      clinical trials of tigecycline. A total of 503 unique S. aureus strains isolated
      from complicated skin and skin structure infections were analyzed. The mecA gene
      was amplified from 120 strains (23.9%) determined to be resistant to oxacillin
      (MICs > or = 4 microg/ml). The prevalence of the mecA gene was found to vary
      regionally from 6.5% to 50.9% among isolates originating in Eastern Europe and
      North America, respectively. The presence of a tetracycline resistance
      determinant, tet(M) or tet(K), among methicillin-resistant S. aureus (MRSA)
      isolates also varied regionally, with a range of 11.9% to 46.2% among isolates
      tested from North America and Eastern Europe, respectively. The occurrence of a
      tetracycline resistance marker in methicillin-susceptible S. aureus (MSSA)
      strains varied from 2.5 to 16.1% among the isolates tested across the regions of
      study. The presence of tet(M) or tet(K) had no discernible effect on the
      tigecycline MICs for either MRSA or MSSA strains, which is consistent with the
      ability of the glycylcyclines to retain activity in the presence of both the
      ribosomal protection and efflux mechanisms of resistance to the tetracyclines.

PMID- 16436704
TI  - Human immunoglobulin G recognizing fibrinogen-binding surface proteins is
      protective against both Staphylococcus aureus and Staphylococcus epidermidis
      infections in vivo.
AB  - A human donor-selected immunoglobulin G for intravenous injection (IGIV) product
      with elevated titers against the staphylococcal fibrinogen-binding MSCRAMM
      proteins ClfA and SdrG (INH-A21) was tested in vitro and in vivo. INH-A21
      contained a significantly increased ability to inhibit the fibrinogen-binding
      activity of recombinant forms of both ClfA and SdrG. Evaluation of the opsonizing
      potential of INH-A21 was evaluated using fluorescently labeled bacteria; this
      assay indicated an increase in phagocytic activity compared to normal IGIV. The
      prophylactic efficacy of INH-A21 against an intraperitoneal challenge of
      methicillin-resistant Staphylococcus epidermidis (MRSE) was evaluated in a
      neonatal rat model. INH-A21 was also evaluated for prophylactic and therapeutic
      efficacy in a rabbit model of catheter-induced aortic valve infective
      endocarditis caused by either MRSE or methicillin-resistant Staphylococcus aureus
      (MRSA). Results from the in vivo models demonstrated potent prophylactic and
      therapeutic efficacy against both MRSE and MRSA. These data suggest that INH-A21
      may be an important tool for the prevention and treatment of staphylococcal
      infections, especially in high-risk populations.

PMID- 16436705
TI  - Discovery of FabH/FabF inhibitors from natural products.
AB  - Condensing enzymes are essential in type II fatty acid synthesis and are
      promising targets for antibacterial drug discovery. Recently, a new approach
      using a xylose-inducible plasmid to express antisense RNA in Staphylococcus
      aureus has been described; however, the actual mechanism was not delineated. In
      this paper, the mechanism of decreased target protein production by expression of
      antisense RNA was investigated using Northern blotting. This revealed that the
      antisense RNA acts posttranscriptionally by targeting mRNA, leading to 5' mRNA
      degradation. Using this technology, a two-plate assay was developed in order to
      identify FabF/FabH target-specific cell-permeable inhibitors by screening of
      natural product extracts. Over 250,000 natural product fermentation broths were
      screened and then confirmed in biochemical assays, yielding a hit rate of 0.1%.
      All known natural product FabH and FabF inhibitors, including cerulenin,
      thiolactomycin, thiotetromycin, and Tu3010, were discovered using this whole-cell
      mechanism-based screening approach. Phomallenic acids, which are new inhibitors
      of FabF, were also discovered. These new inhibitors exhibited target selectivity
      in the gel elongation assay and in the whole-cell-based two-plate assay.
      Phomallenic acid C showed good antibacterial activity, about 20-fold better than
      that of thiolactomycin and cerulenin, against S. aureus. It exhibited a spectrum
      of antibacterial activity against clinically important pathogens including
      methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Haemophilus
      influenzae.

PMID- 16436706
TI  - Inhibition of the autolytic system by vancomycin causes mimicry of vancomycin
      intermediate Staphylococcus aureus-type resistance, cell concentration dependence
      of the MIC, and antibiotic tolerance in vancomycin-susceptible S. aureus.
AB  - Treatment of the fully vancomycin-susceptible Staphylococcus aureus strain COL
      with subinhibitory concentrations of vancomycin allowed its continued growth but
      generated a phenotype reminiscent of some S. aureus isolates with vancomycin
      intermediate S. aureus (VISA)-type resistance: the bacteria grew in multicellular
      clusters; electron microscopy showed inhibition of cell separation and
      accumulation of amorphous cell wall-like material at the bacterial surface.
      Titration of free vancomycin showed a gradual disappearance of the drug from the
      medium, which--eventually--coincided with an increase in the growth rate, burst
      in viable titer, and dispersal of cellular clusters. Addition of inhibitory
      concentrations of vancomycin to the same strain at a higher cell concentration
      caused a very different--antibiotic-tolerant--response: an immediate halt in
      growth, followed by a prolonged lag, during which there was neither a loss of
      viable titer or optical density nor a change in cell morphology but a gradual
      removal of vancomycin from the medium to the cell wall of the bacterium, from
      which the antibiotic could be recovered in a biologically active form.
      Eventually, the drug-treated culture resumed normal growth. The transient
      appearance of both the VISA phenotype and vancomycin tolerance could be traced to
      the inhibition of the autolytic system of the bacterium by vancomycin molecules
      attached to the cell wall, blocking the access of a staphylococcal murein
      hydrolase(s) to its cell wall substrate.

PMID- 16436707
TI  - Horizontal transfer of blaCMY-bearing plasmids among clinical Escherichia coli
      and Klebsiella pneumoniae isolates and emergence of cefepime-hydrolyzing CMY-19.
AB  - Nine Escherichia coli and 5 Klebsiella pneumoniae clinical isolates resistant to
      various cephalosporins and cephamycins were identified in a Japanese general
      hospital between 1995 and 1997. All nine E. coli isolates and one K. pneumoniae
      isolate carried bla(CMY-9), while the other four K. pneumoniae isolates harbored
      a variant of bla(CMY-9), namely, bla(CMY-19). The pulsed-field gel
      electrophoresis patterns of the nine CMY-9-producing E. coli isolates were almost
      identical, suggesting their clonal relatedness, while those of the five K.
      pneumoniae isolates were divergent. Plasmid profiles, Southern hybridization, and
      conjugation assays revealed that the genes for the CMY-9 and the CMY-19 beta
      lactamases were located on very similar conjugative plasmids in E. coli and K.
      pneumoniae. The genetic environment of bla(CMY-19) was identical to that of
      bla(CMY-9). A single amino acid substitution, I292S, adjacent to the H-10 helix
      region was observed between CMY-9 and CMY-19. This substitution was suggested to
      be responsible for the expansion of the hydrolyzing activity against several
      broad-spectrum cephalosporins, and this finding was consistent with the kinetic
      parameters determined with purified enzymes. These findings suggest that the
      bla(CMY-19) genes found in the four K. pneumoniae isolates might have originated
      from bla(CMY-9) gene following a point mutation and dispersed among genetically
      different K. pneumoniae isolates via a large transferable plasmid.

PMID- 16436708
TI  - Influence of apigenin on gtf gene expression in Streptococcus mutans UA159.
AB  - Apigenin, a potent inhibitor of glucosyltransferase activity, affects the
      accumulation of Streptococcus mutans biofilms in vitro by reducing the formation
      of insoluble glucans and enhancing the soluble glucan content of the
      polysaccharide matrix. In the present study, we investigated the influence of
      apigenin on gtfB, gtfC, and gtfD expression in S. mutans UA159. Apigenin (0.1 mM)
      significantly decreased the expression of gtfB and gtfC mRNA (P < 0.05); in
      contrast, it increased the expression of gtfD in S. mutans growing in the
      planktonic state. The protein levels of GTF B, GTF C, and GTF D in culture
      supernatants were also affected; less GTF B and C were detected, whereas the
      level of GTF D was significantly elevated (P < 0.05). A similar profile of gtf
      expression was obtained with biofilms, although an elevated concentration (1 mM)
      of apigenin was required to elicit the effects. The influence of apigenin on gtf
      gene expression was independent of any effect on GTF activity, did not involve
      inhibition of growth or effects on pH, and was not affected by addition of
      sucrose. The data show that apigenin modulates the genetic expression of
      virulence factors in S. mutans.

PMID- 16436709
TI  - Inhibition of human immunodeficiency virus type 1 replication in latently
      infected cells by a novel IkappaB kinase inhibitor.
AB  - In human immunodeficiency virus type 1 (HIV-1) latently infected cells, NF-kappaB
      plays a major role in the transcriptional induction of HIV-1 replication. Hence,
      downregulation of NF-kappaB activation has long been sought for effective anti
      HIV therapy. Tumor necrosis factor alpha (TNF-alpha) stimulates IkappaB kinase
      (IKK) complex, a critical regulator in the NF-kappaB signaling pathway. A novel
      IKK inhibitor, ACHP {2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4
      piperidin-4-yl-nicotinonitrile}, was developed and evaluated as a potent and
      specific inhibitor for IKK-alpha and IKK-beta. In this study, we examined the
      ability of this compound to inhibit HIV-1 replication in OM10.1 cells latently
      infected with HIV. When these cells were pretreated with ACHP, TNF-alpha-induced
      HIV-1 replication was dramatically inhibited, as measured by the HIV p24 antigen
      levels in the culture supernatants. Its 50% effective concentration was
      approximately 0.56 microM, whereas its 50% cytotoxic concentration was about 15
      microM. Western blot analysis revealed inhibition of IkappaBalpha
      phosphorylation, IkappaBalpha degradation, p65 nuclear translocation, and p65
      phosphorylation. ACHP was also found to suppress HIV-1 long terminal repeat (LTR)
      driven gene expression through the inhibition of NF-kappaB activation.
      Furthermore, ACHP inhibited TNF-alpha-induced NF-kappaB (p65) recruitment to the
      HIV-1 LTR, as assessed by chromatin immunoprecipitation assay. These findings
      suggest that ACHP acts as a potent suppressor of TNF-alpha-induced HIV
      replication in latently infected cells and that this inhibition is mediated
      through suppression of IKK activity.

PMID- 16436711
TI  - Novel yeast cell-based assay to screen for inhibitors of human cytomegalovirus
      protease in a high-throughput format.
AB  - The protease encoded by the human cytomegalovirus (HCMV) is an attractive target
      for antiviral drug development because of its essential function in viral
      replication. We describe here a cellular assay in the yeast Saccharomyces
      cerevisiae for the identification of small molecule inhibitors of HCMV protease
      by conditional growth in selective medium. In this system, the protease cleavage
      sequence is inserted into the N-(5'-phosphoribosyl)anthranilate isomerase
      (Trp1p), a yeast protein essential for cell proliferation in the absence of
      tryptophan. Coexpression of HCMV protease with the engineered Trp1p substrate in
      yeast cells results in site-specific cleavage and functional inactivation of the
      Trp1p enzyme, thereby leading to an arrest of cell proliferation. This growth
      arrest can be suppressed by the addition of validated HCMV protease inhibitors.
      The growth selection system presented here provides the basis for a high
      throughput screen to identify HCMV protease inhibitors that are active in
      eukaryotic cells.

PMID- 16436710
TI  - 3,5-dioxopyrazolidines, novel inhibitors of UDP-N- acetylenolpyruvylglucosamine
      reductase (MurB) with activity against gram-positive bacteria.
AB  - A series of 3,5-dioxopyrazolidines was identified as novel inhibitors of UDP-N
      acetylenolpyruvylglucosamine reductase (MurB). Compounds 1 to 3, which are 1,2
      bis(4-chlorophenyl)-3,5-dioxopyrazolidine-4-carboxamides, inhibited Escherichia
      coli MurB, Staphyloccocus aureus MurB, and E. coli MurA with 50% inhibitory
      concentrations (IC50s) in the range of 4.1 to 6.8 microM, 4.3 to 10.3 microM, and
      6.8 to 29.4 microM, respectively. Compound 4, a C-4-unsubstituted 1,2-bis(3,4
      dichlorophenyl)-3,5-dioxopyrazolidine, showed moderate inhibitory activity
      against E. coli MurB, S. aureus MurB, and E. coli MurC (IC50s, 24.5 to 35
      microM). A fluorescence-binding assay indicated tight binding of compound 3 with
      E. coli MurB, giving a dissociation constant of 260 nM. Structural
      characterization of E. coli MurB was undertaken, and the crystal structure of a
      complex with compound 4 was obtained at 2.4 A resolution. The crystal structure
      indicated the binding of a compound at the active site of MurB and specific
      interactions with active-site residues and the bound flavin adenine dinucleotide
      cofactor. Peptidoglycan biosynthesis studies using a strain of Staphylococcus
      epidermidis revealed reduced peptidoglycan biosynthesis upon incubation with 3,5
      dioxopyrazolidines, with IC50s of 0.39 to 11.1 microM. Antibacterial activity was
      observed for compounds 1 to 3 (MICs, 0.25 to 16 microg/ml) and 4 (MICs, 4 to 8
      microg/ml) against gram-positive bacteria including methicillin-resistant S.
      aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant
      Streptococcus pneumoniae.

PMID- 16436712
TI  - Nonmolecular test for detection of low-level resistance to fluoroquinolones in
      Streptococcus pneumoniae.
AB  - With respect to pneumococci, there is a need to detect first-step mutants with
      reduced fluoroquinolone (FQ) susceptibility from which second-step, resistant
      mutants are likely to be selected in the presence of antipneumococcal FQs. Here,
      we describe an interpretative disk diffusion test, of which three options are
      presented, that allows the distinction between first- and second-step mutants.
      Using five FQ disks (pefloxacin, norfloxacin, levofloxacin, ciprofloxacin, and
      sparfloxacin, option 1), all known mechanisms of altered FQ susceptibility found
      in first-step mutants (ParC, ParE, GyrA, or efflux) and in second-step mutants
      (ParC and GyrA or ParE and GyrA) can be accurately detected, making this option a
      useful epidemiological tool. Using three FQ disks (pefloxacin, norfloxacin, and
      levofloxacin, option 2), the most prevalent FQ-resistant mutants, but not the
      first-step GyrA mutants, can be detected. With only two FQ disks (norfloxacin and
      levofloxacin) in the third and simplest option, first-step mutants can be
      distinguished from second-step mutants, however, without differentiation of ParC,
      ParE, or efflux alterations.

PMID- 16436713
TI  - Fluconazole treatment is effective against a Candida albicans erg3/erg3 mutant in
      vivo despite in vitro resistance.
AB  - Candida albicans ERG3 encodes a sterol C5,6-desaturase which is essential for
      synthesis of ergosterol. Defective sterol C5,6 desaturation has been considered
      to be one of the azole resistance mechanisms in this species. However, the
      clinical relevance of this resistance mechanism is still unclear. In this study,
      we created a C. albicans erg3/erg3 mutant by the "Ura-blaster" method and
      confirmed the expected azole resistance using standard in vitro testing and the
      presence of ergosta-7,22-dien-3beta-ol instead of ergosterol. For in vivo
      studies, a wild-type URA3 was placed back into its native locus in the erg3
      homozygote to avoid positional effects on URA3 expression. Defective hyphal
      formation of the erg3 homozygote was observed not only in vitro but in kidney
      tissues. A marked attenuation of virulence was shown by the longer survival and
      the lower kidney burdens of mice inoculated with the reconstituted Ura+ erg3
      homozygote relative to the control. To assess fluconazole efficacy in a murine
      model of disseminated candidiasis, inoculum sizes of the control and the erg3
      homozygote were chosen which provided a similar organ burden. Under these
      conditions, fluconazole was highly effective in reducing the organ burden in both
      groups. This study demonstrates that an ERG3 mutation causing inactivation of
      sterol C5,6-desaturase cannot confer fluconazole resistance in vivo by itself
      regardless of resistance measured by standard in vitro testing. The finding
      questions the clinical significance of this resistance mechanism.

PMID- 16436714
TI  - Loss of the homotypic fusion and vacuole protein sorting or golgi-associated
      retrograde protein vesicle tethering complexes results in gentamicin sensitivity
      in the yeast Saccharomyces cerevisiae.
AB  - Gentamicin continues to be a primary antibiotic against gram-negative infections.
      Unfortunately, associated nephro- and ototoxicity limit its use. Our previous
      mammalian studies showed that gentamicin is trafficked to the endoplasmic
      reticulum in a retrograde manner and subsequently released into the cytosol. To
      better dissect the mechanism through which gentamicin induces toxicity, we have
      chosen to study its toxicity using the simple eukaryote Saccharomyces cerevisiae.
      A recent screen of the yeast deletion library identified multiple gentamicin
      sensitive strains, many of which participate in intracellular trafficking. Our
      approach was to evaluate gentamicin sensitivity under logarithmic growth
      conditions. By quantifying growth inhibition in the presence of gentamicin, we
      determined that several of the sensitive strains were part of the Golgi
      associated retrograde protein (GARP) and homotypic fusion and vacuole protein
      sorting (HOPS) complexes. Further evaluation of their other components showed
      that the deletion of any GARP member resulted in gentamicin-hypersensitive
      strains, while the deletion of other HOPS members resulted in less gentamicin
      sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity
      included ZUO1, SAC1, and NHX1. Finally, we utilized a Texas Red gentamicin
      conjugate to characterize gentamicin uptake and localization in both gentamicin
      sensitive and -insensitive strains. These studies were consistent with our
      mammalian studies, suggesting that gentamicin toxicity in yeast results from
      alterations to intracellular trafficking pathways. The identification of genes
      whose absence results in gentamicin toxicity will help target specific pathways
      and mechanisms that contribute to gentamicin toxicity.

PMID- 16436715
TI  - In vivo transfer of the vanA resistance gene from an Enterococcus faecium isolate
      of animal origin to an E. faecium isolate of human origin in the intestines of
      human volunteers.
AB  - Transient colonization by vancomycin-resistant enterococci of animal origin has
      been documented in the intestines of humans. However, little is known about
      whether transfer of the vanA gene occurs in the human intestine. Six volunteers
      ingested a vancomycin-resistant Enterococcus faecium isolate of chicken origin,
      together with a vancomycin-susceptible E. faecium recipient of human origin.
      Transconjugants were recovered in three of six volunteers. In one volunteer, not
      only was vancomycin resistance transferred, but also quinupristin-dalfopristin
      resistance. This study shows that transfer of the vanA gene from an E. faecium
      isolate of animal origin to an E. faecium isolate of human origin can occur in
      the intestines of humans. It suggests that transient intestinal colonization by
      enterococci carrying mobile elements with resistance genes represents a risk for
      spread of resistance genes to other enterococci that are part of the human
      indigenous flora, which can be responsible for infections in certain groups of
      patients, e.g., immunocompromised patients.

PMID- 16436716
TI  - Role of the extended alpha4 domain of Staphylococcus aureus gyrase A protein in
      determining low sensitivity to quinolones.
AB  - Fluoroquinolones target two bacterial type II topoisomerases, DNA gyrase and
      topoisomerase IV. Acquired resistance to quinolones occurs stepwise, with the
      first mutation occurring in the more sensitive target enzyme. To limit the
      emergence of resistance, quinolones should ideally possess dual activities
      against the two enzymes. For reasons that are as yet unclear, Staphylococcus
      aureus gyrase is less sensitive to quinolones than topoisomerase IV, counter to
      its greater sensitivity in Escherichia coli, thereby limiting the use of
      quinolones for the treatment of staphylococcal infections. Mutations in the
      alpha4-helix domain of the GyrA subunit of gyrase are important in determining
      quinolone resistance. We replaced an extended region encompassing the alpha4
      domain in the E. coli GyrA protein with its homolog in S. aureus and tested for
      its ability to complement a thermosensitive gyrase and its catalytic and
      noncatalytic properties. Purified gyrase reconstituted with chimeric GyrA was
      more resistant to ciprofloxacin than wild-type gyrase at both inhibition of
      catalytic activity and stimulation of cleavage complexes, and this difference was
      more apparent in the presence of K+-glutamate. The chimeric GyrA subunit was able
      to complement thermosensitive gyrase, similar to wild-type GyrA. Without
      supplemental K+-glutamate the MICs of ciprofloxacin for thermosensitive E. coli
      complemented with chimeric DNA gyrase were equal to those for E. coli
      complemented with wild-type gyrase but were twofold higher in the presence of K+
      glutamate. Our findings suggest that the extended alpha4 domain of S. aureus GyrA
      is responsible, at least in part, for the increased resistance of S. aureus
      gyrase to quinolones and that this effect is modulated by K+-glutamate.

PMID- 16436717
TI  - Emergence of DHA-1-producing Klebsiella spp. in the Parisian region: genetic
      organization of the ampC and ampR genes originating from Morganella morganii.
AB  - Eleven Klebsiella pneumoniae clinical isolates and one Klebsiella oxytoca
      clinical isolate showing various pulsed-field gel electrophoresis types and
      producing an inducible DHA-1 class C beta-lactamase were isolated in the Parisian
      region between 1998 and 2003. The aim of this study was to compare the genetic
      organization of the bla(DHA-1) genes in this collection of clinical isolates. In
      four isolates, the Morganella morganii-derived genomic region containing bla(DHA
      1) was inserted in an entire complex sul1-type integron, including a region
      common to In6-In7 (CR1), as previously described in a bla(DHA-1)-producing
      Salmonella enterica serovar Enteritidis KF92 isolate from Saudi Arabia in 1992.
      Different gene cassette arrays were characterized in each of these integrons. In
      two of them, an additional 10-kb fragment was inserted between the CR1 and the M.
      morganii-derived region and was similar to the sap (ABC transporter family) and
      psp (phage shock protein) operons originated from Salmonella enterica serovar
      Typhimurium. The length of the M. morganii region was variable, suggesting that
      several independent recombination events have occurred and that open reading
      frame orf513 encodes a recombinase involved in the mobilization of the resistance
      genes. The genetic organization of bla(DHA-1) was identical in the eight other
      isolates. This structure is likely derived from a complex integron following the
      insertion of IS26, leading to the deletion of the first part of integron. The
      horizontal transfer of one plasmid carrying that truncated integron was shown for
      seven of these isolates.

PMID- 16436718
TI  - CMY-16, a novel acquired AmpC-type beta-lactamase of the CMY/LAT lineage in
      multifocal monophyletic isolates of Proteus mirabilis from northern Italy.
AB  - We report multifocal detection (four different cities in northern Italy) of
      Proteus mirabilis isolates resistant to both oxyimino- and 7-alpha-methoxy
      cephalosporins and producing a novel acquired AmpC-like beta-lactamase. The
      enzyme, named CMY-16, is a variant of the CMY/LAT lineage, which differs from the
      closest homologues, CMY-4 and CMY-12, by a single amino acid substitution (A171S
      or N363S, respectively) and from CMY-2 by two substitutions (A171S and W221R).
      Expression of the cloned bla(CMY-16) gene in Escherichia coli decreased
      susceptibility to penicillins, cephalosporins, and aztreonam. Tazobactam was more
      effective than clavulanate at antagonizing the enzyme activity. Genotyping, by
      random amplification of polymorphic DNA and pulsed-field gel electrophoresis of
      genomic DNA digested with SfiI, showed that isolates were clonally related to
      each other, although not identical. The bla(CMY-16) gene was not transferable to
      E. coli by conjugation or transformation. In all isolates, it was chromosomally
      located and inserted in a conserved genetic environment. PCR mapping experiments
      revealed that the bla(CMY-16) was flanked by ISEcp1 and the blc gene, similar to
      other genes of this lineage from plasmids of Salmonella enterica, Klebsiella
      spp., and E. coli. Overall, these results revealed multifocal spreading of a CMY
      16-producing P. mirabilis clone in northern Italy. This finding represents the
      first report of an acquired AmpC-like beta-lactamase in Proteus mirabilis from
      Italy and underscores the emergence of similar resistance determinants in the
      European setting.

PMID- 16436719
TI  - In vitro antiretroviral activity and in vitro toxicity profile of SPD754, a new
      deoxycytidine nucleoside reverse transcriptase inhibitor for treatment of human
      immunodeficiency virus infection.
AB  - SPD754 (AVX754) is a deoxycytidine analogue nucleotide reverse transcriptase
      inhibitor (NRTI) in clinical development. These studies characterized the in
      vitro activity of SPD754 against NRTI-resistant human immunodeficiency virus type
      1 (HIV-1) and non-clade B HIV-1 isolates, its activity in combination with other
      antiretrovirals, and its potential myelotoxicity and mitochondrial toxicity.
      SPD754 was tested against 50 clinical HIV-1 isolates (5 wild-type isolates and 45
      NRTI-resistant isolates) in MT-4 cells using the Antivirogram assay. SPD754
      susceptibility was reduced 1.2- to 2.2-fold against isolates resistant to
      zidovudine (M41L, T215Y/F, plus a median of three additional nucleoside analogue
      mutations [NAMs]) and/or lamivudine (M184V) and was reduced 1.3- to 2.8-fold
      against isolates resistant to abacavir (L74V, Y115F, and M184V plus one other
      NAM) or stavudine (V75T/M, M41L, T215F/Y, and four other NAMs). Insertions at
      amino acid position 69 and Q151M mutations (with or without M184V) reduced SPD754
      susceptibility 5.2-fold and 14- to 16-fold, respectively (these changes gave
      values comparable to or less than the corresponding values for zidovudine,
      lamivudine, abacavir, and didanosine). SPD754 showed similar activity against
      isolates of group M HIV-1 clades, including A/G, B, C, D, A(E), D/F, F, and H.
      SPD754 showed additive effects in combination with other NRTIs, tenofovir,
      nevirapine, or saquinavir. SPD754 had no significant effects on cell viability or
      mitochondrial DNA in HepG2 or MT-4 cells during 28-day exposure at concentrations
      up to 200 microM. SPD754 showed a low potential for myelotoxicity against human
      bone marrow. In vitro, SPD754 retained activity against most NRTI-resistant HIV-1
      clinical isolates and showed a low propensity to cause myelotoxicity and
      mitochondrial toxicity.

PMID- 16436720
TI  - Safety and pharmacokinetics of intravenous anidulafungin in children with
      neutropenia at high risk for invasive fungal infections.
AB  - Anidulafungin is an echinocandin with activity against Candida species and
      Aspergillus species. Adult dosages under study are 50 mg/day for esophageal
      candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is
      known, however, about the safety and pharmacokinetics of anidulafungin in
      children. A multicenter, ascending-dosage study of neutropenic pediatric patients
      was therefore conducted. Patients were divided into two age cohorts (2 to 11
      years and 12 to 17 years) and were enrolled into sequential groups to receive
      0.75 or 1.5 mg/kg of body weight/day. Blood samples were obtained following the
      first and fifth doses. Anidulafungin was assayed in plasma, and pharmacokinetic
      parameters were determined. Safety was assessed using National Cancer Institute
      (NCI) common toxicity criteria. Pharmacokinetic parameters were determined for 12
      patients at each dosage (0.75 mg/kg/day or 1.5 mg/kg/day). Concentrations and
      drug exposures were similar for patients between age cohorts, and weight-adjusted
      clearance was consistent across age. No drug-related serious adverse events were
      observed. One patient had fever (NCI toxicity grade of 3), and one patient had
      facial erythema, which resolved with slowing the infusion rate. Anidulafungin in
      pediatric patients was well tolerated and can be dosed based on body weight.
      Pediatric patients receiving 0.75 mg/kg/day or 1.5 mg/kg/day have anidulafungin
      concentration profiles similar to those of adult patients receiving 50 or 100
      mg/day, respectively.

PMID- 16436722
TI  - Quinolones induce partial or total loss of pathogenicity islands in uropathogenic
      Escherichia coli by SOS-dependent or -independent pathways, respectively.
AB  - Escherichia coli is the most common microorganism causing urinary tract
      infections. Quinolone-resistant E. coli strains have fewer virulence factors than
      quinolone-susceptible strains. Several urovirulence genes are located in
      pathogenicity islands (PAIs). We investigated the capacity of quinolones to
      induce loss of virulence factors such as hemolysin, cytotoxic necrotizing factor
      1, P fimbriae, and autotransporter Sat included in PAIs in three uropathogenic E.
      coli strains. In a multistep selection, all strains lost hemolytic capacity at
      between 1 and 4 passages when they were incubated with subinhibitory
      concentrations of ciprofloxacin, showing a partial or total loss of the PAI
      containing the hly (hemolysin) and cnf-1 (cytotoxic necrotizing factor 1) genes.
      RecA(-) mutants were obtained from the two E. coli strains with partial or total
      loss of the PAI. The inactivation of the RecA protein affected only the partial
      loss of the PAI induced by quinolones. No spontaneous loss of PAIs was observed
      on incubation in the absence of quinolones in either the wild-type or mutant E.
      coli strains. Quinolones induce partial or total loss of PAIs in vitro in
      uropathogenic E. coli by SOS-dependent or -independent pathways, respectively.

PMID- 16436721
TI  - Potencies of human immunodeficiency virus protease inhibitors in vitro against
      Plasmodium falciparum and in vivo against murine malaria.
AB  - Parasite resistance to antimalarial drugs is a serious threat to human health,
      and novel agents that act on enzymes essential for parasite metabolism, such as
      proteases, are attractive targets for drug development. Recent studies have shown
      that clinically utilized human immunodeficiency virus (HIV) protease inhibitors
      can inhibit the in vitro growth of Plasmodium falciparum at or below
      concentrations found in human plasma after oral drug administration. The most
      potent in vitro antimalarial effects have been obtained for parasites treated
      with saquinavir, ritonavir, or lopinavir, findings confirmed in this study for a
      genetically distinct P. falciparum line (3D7). To investigate the potential in
      vivo activity of antiretroviral protease inhibitors (ARPIs) against malaria, we
      examined the effect of ARPI combinations in a murine model of malaria. In mice
      infected with Plasmodium chabaudi AS and treated orally with ritonavir-saquinavir
      or ritonavir-lopinavir, a delay in patency and a significant attenuation of
      parasitemia were observed. Using modeling and ligand docking studies we examined
      putative ligand binding sites of ARPIs in aspartyl proteases of P. falciparum
      (plasmepsins II and IV) and P. chabaudi (plasmepsin) and found that these in
      silico analyses support the antimalarial activity hypothesized to be mediated
      through inhibition of these enzymes. In addition, in vitro enzyme assays
      demonstrated that P. falciparum plasmepsins II and IV are both inhibited by the
      ARPIs saquinavir, ritonavir, and lopinavir. The combined results suggest that
      ARPIs have useful antimalarial activity that may be especially relevant in
      geographical regions where HIV and P. falciparum infections are both endemic.

PMID- 16436723
TI  - Linezolid in prophylaxis against experimental aortic valve endocarditis due to
      Streptococcus oralis or Enterococcus faecalis.
AB  - There are no experimental studies regarding the prophylactic efficacy of
      linezolid against infective endocarditis. Nonbacterial thrombotic endocarditis of
      the aortic valve was induced in rabbits by the insertion of a polyethylene
      catheter. Twenty-four hours later, animals were randomly assigned to a control
      group, and groups receiving either ampicillin (two doses of 40 mg/kg of body
      weight each, given intravenously, 2 h apart) or linezolid (a single per os dose
      of 75 mg/kg). The first dose of ampicillin and the single dose of linezolid were
      administered 0.5 and 1 h, respectively, prior to the intravenous inoculation of
      approximately 10(7) CFU of Streptococcus oralis or Enterococcus faecalis.
      Linezolid peak levels in rabbit serum were similar to the peak serum levels in
      humans following a 600-mg oral dose of linezolid. Linezolid prevented
      endocarditis in 87% of S. oralis-challenged rabbits (P < 0.001 versus controls; P
      = 0.026 versus ampicillin). In rabbits challenged with E. faecalis, linezolid
      prevented endocarditis in 73% (P = 0.003 versus controls; P = 0.049 versus
      ampicillin). Ampicillin prevented endocarditis due to S. oralis or due to E.
      faecalis in 47% (P = 0.005 versus controls) and in 30% (P = not significant
      versus controls) of the challenged animals, respectively. In conclusion,
      linezolid was effective as prophylaxis against endocarditis caused by a strain of
      S. oralis and to a lesser degree against that caused by a strain of E. faecalis.
      Its prophylactic efficacy was superior to that of ampicillin.

PMID- 16436724
TI  - Pharmacokinetics, safety, and efficacy of posaconazole in patients with
      persistent febrile neutropenia or refractory invasive fungal infection.
AB  - The pharmacokinetic profiles, safety, and efficacies of different dosing
      schedules of posaconazole oral suspension in patients with possible, probable,
      and proven refractory invasive fungal infection (rIFI) or febrile neutropenia
      (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six
      patients with FN and 32 patients with rIFI were randomly assigned to one of three
      posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed
      by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg
      b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.).
      Therapy was continued for up to 6 months in patients with rIFI or until
      neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided
      the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001)
      greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively.
      However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12)
      was 52% lower than in non-BMT patients. Treatment-related adverse events
      (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty
      four percent of patients had adverse events leading to premature discontinuation
      (none were treatment related). In efficacy-evaluable patients, successful
      clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg
      b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with
      FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving
      800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800
      mg (400 mg b.i.d.) provide the greatest posaconazole exposure.

PMID- 16436725
TI  - Pharmacokinetics of enfuvirtide in patients treated in typical routine clinical
      settings.
AB  - Therapeutic drug monitoring (TDM) is gaining importance for improving the success
      of antiretroviral treatment in human immunodeficiency virus-infected patients.
      However, enfuvirtide (ENF) concentrations are not regularly determined. The
      objective of this work was to study the pharmacokinetics (PK) of ENF in patients
      treated in routine clinical settings, to develop a population PK model describing
      the concentration-time profile, and to establish PK reference values. A liquid
      chromatography-tandem mass spectrometry method was developed and applied to serum
      samples submitted for TDM. A two-compartment model with linear absorption and
      elimination was fitted to 329 concentrations from 131 patients. The PK model was
      used for simulations resulting in percentile curves for ENF levels for the full
      dosing interval. The model predicted that a median concentration of 1,968 ng/ml
      would be reached 12 h after administration of 90 mg of ENF, and 23% and 58% of
      patients are expected to have concentrations below 1,000 ng/ml and 2,200 ng/ml,
      respectively. Both values have been proposed as cutoffs for virological efficacy.
      The median maximum concentration of drug in serum (Cmax) of 3,943 ng/ml,
      predicted for 3 h after drug administration, is lower than the Cmax reported
      previously. We found an enormous interpatient variability at every time point,
      with concentration spectrums covering >1 log and 52% and 123% interindividual
      variabilities in the typical clearance and volume of distribution, respectively,
      in contrast to preexisting PK data. In summary, ENF levels are lower and more
      variable than expected. Many patients may achieve insufficient concentrations.
      Further covariate analysis in the population PK model might help to identify
      factors influencing the variability in ENF concentrations.

PMID- 16436726
TI  - Pharmacokinetic-pharmacodynamic comparison of amphotericin B (AMB) and two lipid
      associated AMB preparations, liposomal AMB and AMB lipid complex, in murine
      candidiasis models.
AB  - It is generally accepted that the lipid formulations of amphotericin B (AMB) are
      not as potent as conventional AMB on a milligram-per-kilogram basis. We used a
      neutropenic murine disseminated candidiasis model to compare the in vivo
      potencies of AMB, liposomal AMB (L-AMB), and AMB lipid complex (ABLC)
      pharmacodynamically. The pharmacokinetics of the antifungals were examined in
      serum and in three organs commonly seeded in disseminated candidiasis (kidneys,
      liver, and lung). Both single-dose time-kill studies and multiple-dosing-regimen
      studies were used with each of the compounds. Determinations of the numbers of
      CFU in the kidneys were performed following the administration of three
      escalating single doses of the polyenes at various times over 48 h. The areas
      under the time-kill curves (AUTKs) for each dose level of the drugs were compared
      by analysis of variance (ANOVA). In the multiple-dosing-regimen studies with five
      Candida isolates, AMB, L-AMB, and ABLC were administered daily for 72 h. The
      organism burdens in the mouse kidneys were similarly used as the treatment end
      point. Additional multiple regimen-dosing-studies were performed with a single
      Candida albicans isolate, and the microbiologic outcomes in four internal organs
      (kidneys, liver, spleen, and lung) were examined at the end of therapy (48 h).
      The relationship between the dose and the drug exposure expressed by the
      pharmacokinetics of the dosing regimens in serum and organ tissue were analyzed
      by using a maximum-effect model. ANOVA was used to compare the drug exposures
      necessary to achieve the 25% effective dose (ED25), ED50, ED75, and 1 log10
      killing. Comparison of AUTKs suggested that AMB was 4.3- to 5.9-fold more potent
      than either ABLC or L-AMB. The time-kill curves for both lipid formulations were
      very similar. In the multiple-dosing-regimen studies, AMB was 5.0- to 8.0-fold
      more potent than each of the lipid formulations against five Candida isolates in
      the kidneys. Similar differences in potency (5.1- to 7.2-fold) were observed in
      the other end organs. The difference in pharmacokinetics in serum accounted for
      much of the difference in potency between AMB and ABLC (ratio of serum ABLC area
      under the curve of effective doses to serum AMB area under the curve of effective
      doses, 1.2). The differences in the kinetics in the various end organs between
      AMB and L-AMB were better at explaining the disparate potencies at these
      infection sites (ratio of organ L-AMB area under the curve of effective doses to
      organ AMB area under the curve of effective doses, 1.1).

PMID- 16436727
TI  - Involvement of the putative ATP-dependent efflux proteins PatA and PatB in
      fluoroquinolone resistance of a multidrug-resistant mutant of Streptococcus
      pneumoniae.
AB  - The multidrug-resistant mutant Streptococcus pneumoniae M22 constitutively
      overexpresses two genes (patA and patB) that encode proteins homologous to known
      efflux proteins belonging to the ABC transporter family. It is shown here that
      PatA and PatB were strongly induced by quinolone antibiotics and distamycin in
      fluoroquinolone-sensitive strains. PatA was very important for growth of S.
      pneumoniae, and it could not be disrupted in strain M22. PatB appeared to control
      metabolic activity, particularly in amino acid biosynthesis, and it may have a
      pivotal role in coordination of the response to quinolone antibiotics. The
      induction of PatA and PatB by antibiotics showed a pattern similar to that
      exhibited by SP1861, a homologue of ABC-type transporters of choline and other
      osmoprotectants. A second group of quinolone-induced transporter genes comprising
      SP1587 and SP0287, which are homologues of, respectively, oxalate/formate
      antiporters and xanthine or uracil permeases belonging to the major facilitator
      family, showed a different pattern of induction by other antibiotics. There was
      no evidence for the involvement of PmrA, the putative proton-dependent multidrug
      transporter that has been implicated in norfloxacin resistance, in the response
      to quinolone antibiotics in either the resistant mutant or the fluoroquinolone
      sensitive strains.

PMID- 16436728
TI  - Discordances between interpretation algorithms for genotypic resistance to
      protease and reverse transcriptase inhibitors of human immunodeficiency virus are
      subtype dependent.
AB  - The major limitation of drug resistance genotyping for human immunodeficiency
      virus remains the interpretation of the results. We evaluated the concordance in
      predicting therapy response between four different interpretation algorithms
      (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered
      through a worldwide effort to establish a database of non-B subtype sequences,
      and demographic and clinical information about the patients was gathered. The
      most concordant results were found for nonnucleoside reverse transcriptase (RT)
      inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT
      inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially
      for subtypes C and G, the discordances were driven mainly by the protease (PRO)
      mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I
      for subtype G. Subtype F displayed more discordances for ritonavir in untreated
      patients due to the combined presence of PRO 20R and 10I/V. In therapy
      experienced patients, subtype G displayed a lot of discordances for saquinavir
      and indinavir due to mutational patterns involving PRO 90 M and 82I. Subtype F
      had more discordance for nelfinavir attributable to the presence of PRO 88S and
      82A + 54V. For the NRTIs lamivudine and emtricitabine, CRF01_AE had more
      discordances than subtype B due to the presence of RT mutational patterns 65R +
      115 M and 118I + 215Y, respectively. Overall, the different algorithms agreed
      well on the level of resistance scored, but some of the discordances could be
      attributed to specific (subtype-dependent) combinations of mutations. It is not
      yet known whether therapy response is subtype dependent, but the advice given to
      clinicians based on a genotypic interpretation algorithm differs according to the
      subtype.

PMID- 16436729
TI  - Distribution of tetracycline resistance genes in Actinobacillus pleuropneumoniae
      isolates from Spain.
AB  - Actinobacillus pleuropneumoniae is the etiological agent of porcine
      pleuropneumonia. Tetracycline is used for therapy of this disease, and A.
      pleuropneumoniae carrying the tet(B) gene, coding for an efflux protein that
      reduces the intercellular tetracycline level, has been described previously. Of
      the 46 tetracycline-resistant (Tc(r)) Spanish A. pleuropneumoniae isolates used
      in this study, 32 (70%) carried the tet(B) gene, and 30 of these genes were
      associated with plasmids. Eight (17%) isolates carried the tet(O) gene, two (4%)
      isolates carried either the tet(H) or the tet(L) gene, and all these genes were
      associated with plasmids. This is the first description of these tet genes in A.
      pleuropneumoniae. The last two Tc(r) isolates carried none of the tet genes
      examined. Except for tet(O)-containing plasmids, the other 34 Tc(r) plasmids were
      transformable into an Escherichia coli recipient. Two plasmids were completely
      sequenced. Plasmid p11745, carrying the tet(B) gene, was 5,486 bp and included a
      rep gene, encoding a replication-related protein, and two open reading frames
      (ORFs) with homology to mobilization genes of Neisseria gonorrhoeae plasmid
      pSJ7.4. Plasmid p9555, carrying the tet(L) gene, was 5,672 bp and, based on its
      G+C content, consisted of two regions, one of putative gram-positive origin
      containing the tet(L) gene and the other comprising four ORFs organized in an
      operon-like structure with homology to mobilization genes in other plasmids of
      gram-negative bacteria.

PMID- 16436730
TI  - Clinical evaluation of macrolide-resistant Mycoplasma pneumoniae.
AB  - Macrolide-resistant Mycoplasma pneumoniae (MR M. pneumoniae) has been isolated
      from clinical specimens in Japan since 2000. A comparative study was carried out
      to determine whether or not macrolides are effective in treating patients
      infected with MR M. pneumoniae. The clinical courses of 11 patients with MR M.
      pneumoniae infection (MR patients) treated with macrolides were compared with
      those of 26 patients with macrolide-susceptible M. pneumoniae infection (MS
      patients). The total febrile days and the number of febrile days during macrolide
      administration were longer in the MR patients than in the MS patients (median of
      8 days versus median of 5 days [P = 0.019] and 3 days versus 1 day [P = 0.002],
      respectively). In addition, the MR patients were more likely than the MS patients
      to have had a change of the initially prescribed macrolide to another
      antimicrobial agent (63.6% versus 3.8%; odds ratio, 43.8; P < 0.001), which might
      reflect the pediatrician's judgment that the initially prescribed macrolide was
      not sufficiently effective in these patients. Despite the fact that the febrile
      period was prolonged in MR patients given macrolides, the fever resolved even
      when the initial prescription was not changed. These results show that macrolides
      are certainly less effective in MR patients.

PMID- 16436731
TI  - In vitro preclinical testing of nonoxynol-9 as potential anti-human
      immunodeficiency virus microbicide: a retrospective analysis of results from five
      laboratories.
AB  - The first product to be clinically evaluated as a microbicide contained the
      nonionic surfactant nonoxynol-9 (nonylphenoxypolyethoxyethanol; N-9). Many
      laboratories have used N-9 as a control compound for microbicide assays. However,
      no published comparisons of the results among laboratories or attempts to
      establish standardized protocols for preclinical testing of microbicides have
      been performed. In this study, we compared results from 127 N-9 toxicity and 72
      efficacy assays that were generated in five different laboratories over the last
      six years and were performed with 14 different cell lines or tissues. Intra-assay
      reproducibility was measured at two-, three-, and fivefold differences using
      standard deviations. Interassay reproducibility was assessed using general linear
      models, and interaction between variables was studied using step-wise regression.
      The intra-assay reproducibility within the same N-9 concentration, cell type,
      assay duration, and laboratory was consistent at the twofold level of standard
      deviations. For interassay reproducibility, cell line, duration of assay, and N-9
      concentration were all significant sources of variability (P < 0.01). Half
      maximal toxicity concentrations for N-9 were similar between laboratories for
      assays of similar exposure durations, but these similarities decreased with lower
      test concentrations of N-9. Results for both long (>24 h) and short (<2 h)
      exposures of cells to N-9 showed variability, while assays with 4 to 8 h of N-9
      exposure gave results that were not significantly different. This is the first
      analysis to compare preclinical N-9 toxicity levels that were obtained by
      different laboratories using various protocols. This comparative work can be used
      to develop standardized microbicide testing protocols that will help advance
      potential microbicides to clinical trials.

PMID- 16436732
TI  - Rational design of anticytoadherence inhibitors for Plasmodium falciparum based
      on the crystal structure of human intercellular adhesion molecule 1.
AB  - Adhesion of Plasmodium falciparum-infected erythrocytes (IE) to host endothelium
      has been associated with pathology in malaria. Although the interaction with
      endothelial cells can be complex due to the relatively large number of host
      receptors available for binding, specific proteins have been identified that are
      more commonly used than others. For example, binding to intercellular adhesion
      molecule 1 (ICAM 1) is found frequently in parasites from pediatric cases of
      malaria. The binding site for P. falciparum-infected erythrocytes on ICAM 1 has
      been mapped in some detail and is distinct from the site for lymphocyte function
      associated antigen 1 (LFA-1). Part of the ICAM 1 binding site for P. falciparum
      infected erythrocytes (the DE loop) was used to screen a library of compounds
      based on its structure (derived from the crystal structure of human ICAM 1). This
      resulted in the identification of 36 structural mimeotopes as potential
      competitive inhibitors of binding. One of these compounds, (+)-epigalloyl
      catechin-gallate [(+)-EGCG], was found to inhibit IE adhesion to ICAM 1 in a dose
      dependent manner with two variant ICAM 1-binding parasite lines, providing the
      first example of a potential mimeotope-based anticytoadherence inhibitor for
      Plasmodium falciparum.

PMID- 16436733
TI  - Prediction of the evolution of ceftazidime resistance in extended-spectrum beta
      lactamase CTX-M-9.
AB  - A random mutagenesis technique was used to predict the evolutionary potential of
      beta-lactamase CTX-M-9 toward the acquisition of improved catalytic activity
      against ceftazidime. Thirty CTX-M mutants were obtained during three rounds of
      mutagenesis. These mutants conferred 1- to 128-fold-higher MICs of ceftazidime
      than the parental enzyme CTX-M-9. The CTX-M mutants contained one to six amino
      acid substitutions. Mutants harbored the substitutions Asp240Gly and Pro167Ser,
      which were previously observed in clinical CTX-M enzymes. Additional
      substitutions, notably Arg164His, Asp179Gly, and Arg276Ser, were observed near
      the active site. The kinetic constants of the three most active mutants revealed
      two distinct ways of improving catalytic efficiency against ceftazidime. One
      enzyme had a 17-fold-higher k(cat) value than CTX-M-9 against ceftazidime. The
      other two had 75- to 300-fold-lower Km values than CTX-M-9 against ceftazidime.
      The current emergence of CTX-M beta-lactamases with improved activity against
      ceftazidime may therefore be the beginning of an evolutionary process which might
      subsequently generate a great diversity of CTX-M-type ceftazidimases.

PMID- 16436734
TI  - Doxycycline attenuated pulmonary fibrosis induced by bleomycin in mice.
AB  - The administration of doxycycline prior to bleomycin in mice attenuated pulmonary
      fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not
      caseinolytic activity, were attenuated by doxycycline. Established fibrosis was
      not affected by doxycycline. Thus, doxycycline might be useful for slowing down
      pulmonary fibrosis by biological activity other than antibacterial activity.

PMID- 16436735
TI  - Inhibition of Candida parapsilosis mitochondrial respiratory pathways enhances
      susceptibility to caspofungin.
AB  - Among the Candida species, Candida parapsilosis has a unique mitochondrial
      respiratory network. The addition of inhibitors of the respiratory pathways in
      three clinical isolates of C. parapsilosis with high (> or =2- microg/ml) MICs of
      caspofungin significantly (fivefold) decreased caspofungin MICs but did not
      change fluconazole MICs.

PMID- 16436736
TI  - Efficacy of quinolones against secondary pneumococcal pneumonia after influenza
      virus infection in mice.
AB  - We established a mouse model of secondary pneumococcal pneumonia after influenza
      virus infection and investigated the efficacy of several quinolones against
      pneumonia in this model. Gatifloxacin exhibited the highest efficacy among the
      quinolones examined and is probably useful for the treatment of secondary
      bacterial pneumonia.

PMID- 16436737
TI  - Potentiation of catechin gallate-mediated sensitization of Staphylococcus aureus
      to oxacillin by nongalloylated catechins.
AB  - (-)-Epicatechin gallate (ECg) and (-)-epigallocatechin gallate (EGCg) reduce
      oxacillin resistance in mecA-containing strains of Staphylococcus aureus. Their
      binding to staphylococcal cells is enhanced by the nongalloyl analogues (-)
      epicatechin (EC) and (-)-epigallocatechin (EGC). EC and EGC significantly
      increased the capacity of ECg and EGCg to reduce levels of staphylococcal
      oxacillin resistance.

PMID- 16436738
TI  - Occurrence of OXA-58-like carbapenemases in Acinetobacter spp. collected over 10
      years in three continents.
AB  - OXA-58 is a recently described carbapenemase from Acinetobacter spp. in Europe.
      We examined earlier worldwide Acinetobacter collections and found bla(OXA-58) in
      30 carbapenem-nonsusceptible isolates, including several isolates collected in
      Argentina and Kuwait in 1995 and 1996 and in a British outbreak strain from 2000.
      Most isolates (28 of 30) also had bla(OXA-51). We conclude that bla(OXA-58) is
      geographically widespread and has occurred in Acinetobacter spp. for over 10
      years.

PMID- 16436739
TI  - A porphyrin increases survival time of mice after intracerebral prion infection.
AB  - Prion diseases, including scrapie, are incurable neurodegenerative disorders.
      Some compounds can delay disease after a peripheral scrapie inoculation, but few
      are effective against advanced disease. Here, we tested multiple related
      porphyrins, but only Fe(III)meso-tetra(4-sulfonatophenyl)porphine injected into
      mouse brains after intracerebral scrapie inoculation substantially increased
      survival times.

PMID- 16436740
TI  - Practical preclinical model for assessing the potential for unconjugated
      hyperbilirubinemia produced by human immunodeficiency virus protease inhibitors.
AB  - A practical preclinical model for the hyperbilirubinemia produced by human
      immunodeficiency virus protease inhibitors has been developed. Indinavir and
      atazanavir produced significant hyperbilirubinemia, whereas amprenavir, the
      negative control, was indistinguishable from the ritonavir booster dose. This
      model was used to disqualify an exploratory protease inhibitor from development.

PMID- 16436741
TI  - Single- and multistep resistance selection studies on the activity of retapamulin
      compared to other agents against Staphylococcus aureus and Streptococcus
      pyogenes.
AB  - Retapamulin had the lowest rate of spontaneous mutations by single-step passaging
      and the lowest parent and selected mutant MICs by multistep passaging among all
      drugs tested for all Staphylococcus aureus strains and three Streptococcus
      pyogenes strains which yielded resistant clones. Retapamulin has a low potential
      for resistance selection in S. pyogenes, with a slow and gradual propensity for
      resistance development in S. aureus.

PMID- 16436742
TI  - Efficacy of telavancin against penicillin-resistant pneumococci and
      Staphylococcus aureus in a rabbit meningitis model and determination of kinetic
      parameters.
AB  - The penetration of telavancin was 2% into inflamed meninges and ca. 1 per
      thousand into noninflamed meninges after two intravenous injections (30 mg/kg of
      body weight). In experimental meningitis, telavancin was significantly superior
      to vancomycin combined with ceftriaxone against a penicillin-resistant
      pneumococcal strain. Against a methicillin-sensitive staphylococcal strain,
      telavancin was slightly but not significantly superior to vancomycin.

PMID- 16436743
TI  - Effect of ribavirin and glucocorticoid treatment in a mouse model of human
      metapneumovirus infection.
AB  - Human metapneumovirus (hMPV)-infected BALB/c mice were treated with ribavirin (40
      mg/kg of body weight twice a day intraperitoneally), corticosterone (0.2 mg/ml in
      water), or both modalities. Ribavirin significantly decreased both hMPV
      replication in lungs (by 5 log10) and global pulmonary inflammation on day 5
      postinfection, whereas glucocorticoids reduced only alveolar and interstitial
      inflammation, compared to controls.

PMID- 16436744
TI  - Antimicrobial susceptibilities of Campylobacter jejuni isolates from poultry from
      Alberta, Canada.
AB  - One hundred four isolates of Campylobacter jejuni from poultry in Alberta,
      Canada, collected during 2001 were tested for resistance to 10 antimicrobial
      agents using agar dilution. This study provides a baseline of resistance profiles
      and the mechanisms of resistance observed in C. jejuni in poultry from Alberta,
      Canada.

PMID- 16436745
TI  - New TEM-derived extended-spectrum beta-lactamase and its genomic context in
      plasmids from Salmonella enterica serovar derby isolates from Uruguay.
AB  - A small (8.2-kb) ColE1 plasmid encoding TEM-144 (a new beta-lactamase with a
      ceftazidimase profile) was sequenced by a gene-walking strategy. The bla(TEM)
      allele was carried on a Tn2 element, disrupting a Rom protein gene. TEM-144
      differs from TEM-1 by two mutations (R164C and E240K) and from the ceftazidime
      hydrolyzing TEM-91 by one mutation (T182M).

PMID- 16436746
TI  - Emergence of Enterobacteriaceae isolates producing CTX-M extended-spectrum beta
      lactamase in Austria.
AB  - Among 149 extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
      isolates collected from patients in southeast Austria from 1998 to 2004, 38
      Escherichia coli isolates and 11 Klebsiella spp. were CTX-M producers. The
      proportion of CTX-M-producers among all ESBL producers rose from 0% in 1998 to
      58% in 2004. In general, CTX-M-producers had heterogeneous pulsed-field gel
      electrophoresis patterns, but one E. coli isolate was identical to a United
      Kingdom epidemic CTX-M-15-producing strain, although no epidemiological link with
      the United Kingdom was apparent.

PMID- 16436747
TI  - Tissue penetration of telavancin after intravenous administration in healthy
      subjects.
AB  - The pharmacokinetic disposition of telavancin administered 7.5 mg/kg of body
      weight every 24 h was determined in plasma and skin blister fluid. The mean
      penetration of telavancin into blister fluid was 40%. This study reveals that
      adequate concentrations are achieved in both plasma and blister fluid for
      pathogens frequently implicated in skin and soft tissue infections.

PMID- 16436749
TI  - In vitro activity of DX-619, a novel des-fluoro(6) quinolone, against a panel of
      Streptococcus pneumoniae mutants with characterized resistance mechanisms.
AB  - The in vitro activities of DX-619 and four other quinolones were compared against
      Streptococcus pneumoniae mutants that contained a variety of alterations within
      the quinolone resistance-determining regions. DX-619 was the most potent
      quinolone and was least affected by the mutations.

PMID- 16436748
TI  - PCR classification of CTX-M-type beta-lactamase genes identified in clinically
      isolated gram-negative bacilli in Japan.
AB  - Of 1,456 strains isolated from 2001 to 2003 demonstrating resistance to either
      oxyimino-cephalosporin, 317 strains, isolated in 57 of 132 clinical facilities,
      were found to harbor bla(CTX-M) genes by PCR. Fifty-seven, 161, and 99 strains
      harbored bla(CTX-M) genes belonging to the bla(CTX-M-1), bla(CTX-M-2), and
      bla(CTX-M-9) clusters, respectively.

PMID- 16436750
TI  - In117, an unusual In0-like class 1 integron containing CR1 and bla(CTX-M-2) and
      associated with a Tn21-like element.
AB  - An unusual In0-like class 1 integron containing a common region that includes the
      putative recombinase gene named orf513 (CR1) and bla(CTX-M-2) was characterized
      from Escherichia coli. The integron contained an unusual gene cassette array,
      estX-aadA1, embedded between the 5'-conserved segment (5'-CS) and 3'-CS1 regions
      and was flanked by mer-Tn21 sequences downstream of the tni truncated module.
      This element constitutes one of the few examples of CR1-bearing class 1 integrons
      that has been fully characterized.

PMID- 16436751
TI  - Trematocidal activity of praziquantel and artemisinin derivatives: in vitro and
      in vivo investigations with adult Echinostoma caproni.
AB  - We examined the effects of praziquantel and the artemisinins on adult Echinostoma
      caproni. In vitro, both praziquantel and the artemisinins exhibited exposure
      response relationships. In vivo, worm burden reductions of 100% were achieved
      with single oral doses of praziquantel, artesunate, and artemether at 50, 700,
      and 1,100 mg/kg of body weight, respectively.

PMID- 16436752
TI  - In vitro bactericidal activity of human beta-defensin 3 against multidrug
      resistant nosocomial strains.
AB  - The antimicrobial activity of human beta-defensin 3 (hBD-3) against multidrug
      resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium,
      Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii
      was evaluated. A fast bactericidal effect (within 20 min) against all bacterial
      strains tested was observed. The presence of 20% human serum abolished the
      bactericidal activity of hBD-3 against gram-negative strains and reduced the
      activity of the peptide against gram-positive strains.

PMID- 16436754
TI  - Pulsatile delivery of clarithromycin alone or in combination with amoxicillin
      against Streptococcus pneumoniae.
AB  - We evaluated pulsatile dosing of clarithromycin and amoxicillin alone or combined
      against Streptococcus pneumoniae with various susceptibilities. When combined,
      pulsatile amoxicillin with clarithromycin was superior to either 8- or 12-h
      dosing against the intermediate strain and was identical for the susceptible
      strain. Pulse dosing of antimicrobials warrants further investigation.

PMID- 16436753
TI  - Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus
      aureus.
AB  - Piperine, a trans-trans isomer of 1-piperoyl-piperidine, in combination with
      ciprofloxacin markedly reduced the MICs and mutation prevention concentration of
      ciprofloxacin for Staphylococcus aureus, including methicillin-resistant S.
      aureus. The enhanced accumulation and decreased efflux of ethidium bromide in the
      wild-type and mutant (CIPr-1) strains in the presence of piperine suggest its
      involvement in the inhibition of bacterial efflux pumps.

PMID- 16436755
TI  - Streptococcus pyogenes isolates with high-level macrolide resistance and reduced
      susceptibility to telithromycin associated with 23S rRNA mutations.
AB  - Seven high-level macrolide-resistant Streptococcus pyogenes isolates had reduced
      activity to telithromycin but were negative for methylation and efflux genes. All
      were of the constitutive phenotype, were clonally related (emm type 12 and MLST
      type 36), and had identical dual mutations (A2058G and U2166C) in domain V of 23S
      rRNA.

PMID- 16436756
TI  - In vitro activity of doripenem against Pseudomonas aeruginosa and Burkholderia
      cepacia isolates from both cystic fibrosis and non-cystic fibrosis patients.
AB  - The in vitro activities of doripenem, imipenem, levofloxacin, piperacillin,
      ceftazidime, aztreonam, tobramycin, and cefepime were determined for 160 isolates
      of Pseudomonas aeruginosa (82 from cystic fibrosis [CF] patients) and 34 isolates
      of Burkholderia cepacia. Doripenem MIC90s were lower than those of all other
      comparative agents against all isolates combined and against all P. aeruginosa
      isolates. Doripenem was as active as levofloxacin and 2- to 32-fold more active
      than the other comparative agents against B. cepacia.

PMID- 16436757
TI  - Evaluation of high- versus standard-dose rifampin in Indonesian patients with
      pulmonary tuberculosis.

PMID- 16436758
TI  - Tularemia and once-daily gentamicin.

PMID- 16436759
TI  - In vitro activities of polymyxin B, imipenem, and rifampin against multidrug
      resistant Acinetobacter baumannii.

PMID- 16436760
TI  - Images in clinical medicine. The importance of early cervical-spine radiography.

PMID- 16436761
TI  - Beyond fraud--stem-cell research continues.

PMID- 16436762
TI  - Egg donation and human embryonic stem-cell research.

PMID- 16436763
TI  - The physical exam and the sense of smell.

PMID- 16436764
TI  - First, gather the data.

PMID- 16436765
TI  - Ethnic and racial differences in the smoking-related risk of lung cancer.
AB  - BACKGROUND: There is remarkable variation in the incidence of lung cancer among
      ethnic and racial groups in the United States. METHODS: We investigated
      differences in the risk of lung cancer associated with cigarette smoking among
      183,813 African-American, Japanese-American, Latino, Native Hawaiian, and white
      men and women in the Multiethnic Cohort Study. Our analysis included 1979 cases
      of incident lung cancer identified prospectively over an eight-year period,
      between baseline (1993 through 1996) and 2001. RESULTS: The risk of lung cancer
      among ethnic and racial groups was modified by the number of cigarettes smoked
      per day. Among participants who smoked no more than 30 cigarettes per day,
      African Americans and Native Hawaiians had significantly greater risks of lung
      cancer than did the other groups. Among those who smoked no more than 10 and
      those who smoked 11 to 20 cigarettes per day, relative risks ranged from 0.21 to
      0.39 (P<0.001) among Japanese Americans and Latinos and from 0.45 to 0.57
      (P<0.001) among whites, as compared with African Americans. However, at levels
      exceeding 30 cigarettes per day, these differences were not significant.
      Differences in risk associated with smoking were observed among both men and
      women and for all histologic types of lung cancer. CONCLUSIONS: Among cigarette
      smokers, African Americans and Native Hawaiians are more susceptible to lung
      cancer than whites, Japanese Americans, and Latinos.

PMID- 16436766
TI  - Long-term outcome of renal transplantation from older donors.
AB  - BACKGROUND: Long-term survival of kidney grafts from older donors is inferior to
      that of grafts from younger donors. We sought to determine whether selecting
      older kidneys according to their histologic characteristics before implantation
      would positively influence long-term outcome. METHODS: In a prospective cohort
      study, we assessed outcomes among 62 patients who received one or two
      histologically evaluated kidneys from donors older than 60 years of age. These
      outcomes were compared with outcomes among 248 matched recipients of single
      kidney grafts that had not been histologically evaluated and were either from
      donors 60 years of age or younger (124 positive-reference recipients who,
      according to available data, were expected to have an optimal outcome) or from
      those older than 60 years (124 negative-reference recipients, expected to have a
      worse outcome). The primary end point was graft survival. RESULTS: During a
      median period of 23 months, 4 recipients (6 percent) of histologically evaluated
      kidneys progressed to dialysis, as compared with 7 positive-reference recipients
      (6 percent) and 29 negative-reference recipients (23 percent). Graft survival in
      recipients of histologically evaluated kidneys did not differ significantly from
      that of grafts in positive-reference recipients but was superior to that of
      grafts in negative-reference recipients (hazard ratio for graft failure in the
      negative-reference recipients relative to the recipients of histologically
      evaluated kidneys, 3.68; 95 percent confidence interval, 1.29 to 10.52; P=0.02).
      The performance of preimplantation histologic evaluation predicted better
      survival both in the whole study group (P=0.02) and among recipients of kidneys
      from older donors (P=0.01). CONCLUSIONS: The long-term survival of single or dual
      kidney grafts from donors older than 60 years of age is excellent, provided that
      the grafts are evaluated histologically before implantation. This approach may
      help to expand the donor-organ pool for kidney transplantation.

PMID- 16436767
TI  - The risk associated with aprotinin in cardiac surgery.
AB  - BACKGROUND: The majority of patients undergoing surgical treatment for ST
      elevation myocardial infarction receive antifibrinolytic therapy to limit blood
      loss. This approach appears counterintuitive to the accepted medical treatment of
      the same condition--namely, fibrinolysis to limit thrombosis. Despite this
      concern, no independent, large-scale safety assessment has been undertaken.
      METHODS: In this observational study involving 4374 patients undergoing
      revascularization, we prospectively assessed three agents (aprotinin [1295
      patients], aminocaproic acid [883], and tranexamic acid [822]) as compared with
      no agent (1374 patients) with regard to serious outcomes by propensity and
      multivariable methods. (Although aprotinin is a serine protease inhibitor, here
      we use the term antifibrinolytic therapy to include all three agents.) RESULTS:
      In propensity-adjusted, multivariable logistic regression (C-index, 0.72), use of
      aprotinin was associated with a doubling in the risk of renal failure requiring
      dialysis among patients undergoing complex coronary-artery surgery (odds ratio,
      2.59; 95 percent confidence interval, 1.36 to 4.95) or primary surgery (odds
      ratio, 2.34; 95 percent confidence interval, 1.27 to 4.31). Similarly, use of
      aprotinin in the latter group was associated with a 55 percent increase in the
      risk of myocardial infarction or heart failure (P<0.001) and a 181 percent
      increase in the risk of stroke or encephalopathy (P=0.001). Neither aminocaproic
      acid nor tranexamic acid was associated with an increased risk of renal, cardiac,
      or cerebral events. Adjustment according to propensity score for the use of any
      one of the three agents as compared with no agent yielded nearly identical
      findings. All the agents reduced blood loss. CONCLUSIONS: The association between
      aprotinin and serious end-organ damage indicates that continued use is not
      prudent. In contrast, the less expensive generic medications aminocaproic acid
      and tranexamic acid are safe alternatives.

PMID- 16436768
TI  - A national evaluation of the effect of trauma-center care on mortality.
AB  - BACKGROUND: Hospitals have difficulty justifying the expense of maintaining
      trauma centers without strong evidence of their effectiveness. To address this
      gap, we examined differences in mortality between level 1 trauma centers and
      hospitals without a trauma center (non-trauma centers). METHODS: Mortality
      outcomes were compared among patients treated in 18 hospitals with a level 1
      trauma center and 51 hospitals non-trauma centers located in 14 states. Patients
      18 to 84 years old with a moderate-to-severe injury were eligible. Complete data
      were obtained for 1104 patients who died in the hospital and 4087 patients who
      were discharged alive. We used propensity-score weighting to adjust for
      observable differences between patients treated at trauma centers and those
      treated at non-trauma centers. RESULTS: After adjustment for differences in the
      case mix, the in-hospital mortality rate was significantly lower at trauma
      centers than at non-trauma centers (7.6 percent vs. 9.5 percent; relative risk,
      0.80; 95 percent confidence interval, 0.66 to 0.98), as was the one-year
      mortality rate (10.4 percent vs. 13.8 percent; relative risk, 0.75; 95 percent
      confidence interval, 0.60 to 0.95). The effects of treatment at a trauma center
      varied according to the severity of injury, with evidence to suggest that
      differences in mortality rates were primarily confined to patients with more
      severe injuries. CONCLUSIONS: Our findings show that the risk of death is
      significantly lower when care is provided in a trauma center than in a non-trauma
      center and argue for continued efforts at regionalization.

PMID- 16436769
TI  - Clinical practice. Preventing nephropathy induced by contrast medium.

PMID- 16436770
TI  - Aneurysmal subarachnoid hemorrhage.

PMID- 16436771
TI  - Images in clinical medicine. Radiographic evidence linking tobacco use and lung
      cancer.

PMID- 16436772
TI  - Case records of the Massachusetts General Hospital. Case 3-2006. A 63-year-old
      woman with jaundice and a pancreatic mass.

PMID- 16436773
TI  - Dissecting racial and ethnic differences.

PMID- 16436774
TI  - Maximizing the success of transplantation with kidneys from older donors.

PMID- 16436775
TI  - The value of phase 4 clinical testing.

PMID- 16436776
TI  - Incidence and outcomes of acute lung injury.

PMID- 16436777
TI  - Low HDL cholesterol levels.

PMID- 16436778
TI  - Medical mystery: extensive ecchymosis--the answer.

PMID- 16436779
TI  - Cabergoline and mitral regurgitation.

PMID- 16436780
TI  - Self-reported race and genetic admixture.

PMID- 16436781
TI  - LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs.

PMID- 16436782
TI  - LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews.

PMID- 16436783
TI  - The way of the honeybee.

PMID- 16436784
TI  - Prion 2005: Between Fundamentals and Society's Needs.
AB  - Prion diseases for the most part affect individuals older than 60 years of age
      and share features with other diseases characterized by protein deposits in the
      brain, such as Alzheimer's disease and Parkinson's disease. The international
      conference "Prion 2005: Between Fundamentals and Society's Needs," organized by
      the German Transmissible Spongiform Encephalopathies Research Platform, aimed to
      integrate and coordinate the research efforts of participants to better achieve
      prevention, treatment, control, and management of prion diseases, including
      Creutzfeldt-Jakob disease and fatal familial insomnia in humans. Several main
      topics were discussed, such as the molecular characteristics of prion strains,
      the cell biology of cellular and pathogenic forms of the prion proteins, the
      pathogenesis of the diseases they cause, emerging problems, and promising
      approaches for therapy and new diagnostic tools. The presentations at the Prion
      2005 conference provided new insights in both basic and applied research, which
      will have broad implications for society's needs.

PMID- 16436785
TI  - Stuck in neutral: continued challenges with healthcare disparities.

PMID- 16436786
TI  - IOM report: Improving Medical Education--Enhancing the Behavioral and Social
      Science Content of Medical School Curricula.

PMID- 16436788
TI  - North American coral snake antivenin for the neutralization of non-native elapid
      venoms in a murine model.
AB  - OBJECTIVES: North American coral snake antivenin (CSAV; Wyeth Antivenin [Micrurus
      fulvius], equine origin) is approved for the treatment of coral snake
      envenomations in the United States. The coral snake is the only elapid that is
      native to North America, but envenomations from non-native elapids are occurring
      more commonly in this country. This study was designed to evaluate the efficacy
      of CSAV in the neutralization of two exotic elapid envenomations: Naja naja
      (Indian cobra) and Dendroaspis polylepsis (black mamba). METHODS: A randomized,
      blinded, placebo-controlled murine model of intraperitoneal venom injection was
      employed. Venom potency was determined in preliminary dosing studies. Study
      animals then were divided into five groups: 1) N. naja venom + CSAV, 2) N. naja
      venom + 0.9% normal saline (NS), 3) D. polylepsis venom + CSAV, 4) D. polylepsis
      venom + NS, and 5) CSAV + NS. The venom dose was chosen to be twice the estimated
      LD50. The amount of CSAV injected was ten times the amount necessary for
      neutralization of a 2 x LD50 dose of M. f. fulvius venom in a murine model.
      Statistical analysis included Fisher's exact and log-rank testing to compare
      survival rates and times. RESULTS: Preliminary studies estimated the venom LD50
      to be 2.58 mg/kg and 0.45 mg/kg, respectively, for the N. naja and D. polylepsis.
      A significant difference was shown in comparison of survival times between CSAV
      venom groups and normal saline-venom groups despite all animals in both treatment
      and control arms dying. Animals receiving CSAV and N. naja venom survived (mean
      +/- SD) 24.4 +/- 3.0 minutes, versus 17.8 +/- 1.3 minutes in the control group (p
      < 0.001), whereas those receiving CSAV and D. polylepsis venom survived 203.8 +/-
      37.0 minutes versus 130.0 +/- 42.6 minutes in the control group (p < 0.001). All
      animals in the CSAV + NS group survived to the conclusion of the study.
      CONCLUSIONS: When premixed with venom, CSAV increased survival time in a murine
      model of intraperitoneal N. naja and D. polylepsis venom injection. The clinical
      implications of this are unclear, given unchanged mortality rates.

PMID- 16436787
TI  - Bench to bedside: evidence for brain injury after concussion--looking beyond the
      computed tomography scan.
AB  - The emergency management of cerebral concussion typically centers on the decision
      to perform a head computed tomography (CT) scan, which only rarely detects
      hemorrhagic lesions requiring neurosurgery. The absence of hemorrhage on CT scan
      often is equated with a lack of brain injury. However, observational studies
      revealing poor long-term cognitive outcome after concussion suggest that brain
      injury may be present despite a normal CT scan. To explore this idea further, the
      authors reviewed the evidence for objective neurologic injury in humans after
      concussion, with particular emphasis on those with a normal brain CT. This
      evidence comes from studies involving brain tissue pathology, CT scanning,
      magnetic resonance image (MRI) scanning, serum biomarkers, formal cognitive and
      balance tests, functional MRI, positron emission tomography, and single-photon
      emission computed tomography scanning. Each section is accompanied by technical
      information to help the reader understand what these tests are, not to endorse
      their use clinically. The authors discuss the strengths and weaknesses of the
      evidence in each case. These reports make a compelling case for the existence of
      concussion as a clinically relevant disease with demonstrable neurologic
      pathology. Areas for future emergency medicine research are suggested.

PMID- 16436789
TI  - The emergency department: first line of defense in preventing secondary stroke.
AB  - Stroke and transient ischemic attack (TIA) are increasingly common conditions
      that are associated with significant morbidity and mortality. The strongest
      predictor of recurrent stroke risk is an initial stroke or TIA; in fact, nearly
      30% of all strokes are recurrent events. It is often the emergency department
      (ED) physician who, while treating the initial event, has the first opportunity
      to initiate effective preventive strategies, including pharmacotherapy and
      behavior modification. Evidence- and consensus-based guidelines are well
      established for the use of antiplatelet medications, anticoagulants, and
      antihypertensives for prevention of secondary stroke. Recent evidence suggests
      that the use of statins may be associated with improved clinical outcomes after
      ischemic stroke. In addition, behavioral interventions, such as smoking
      cessation, exercise, diet, and stroke education, can help patients avoid stroke
      recurrence. By initiating prevention therapies during the acute stroke or TIA
      encounter, EPs convey the message to patients that these therapies are important
      for the prevention of recurrent events and are an essential part of the
      treatment.

PMID- 16436790
TI  - The effect of triage-applied Ottawa Ankle Rules on the length of stay in a
      Canadian urgent care department: a randomized controlled trial.
AB  - OBJECTIVES: To determine whether triage nurses ordering ankle or foot radiographs
      according to the Ottawa Ankle Rules (OAR) before physician evaluation decreases
      the length of stay for patients visiting an urgent care department. METHODS: From
      July to September 2004, a randomized controlled trial of consecutive adult
      patients with ankle or foot twisting injuries who arrived at an urgent care
      department was conducted. Patients were included if their age was 18 years or
      older and their injury had occurred within seven days. They were excluded if
      there were neurovascular deficits, limb deformities, open fractures, or
      nonisolated ankle or foot injuries. Patients were randomly allocated to a
      roentgenogram-ordering clinical pathway (intervention) or to standard
      departmental care (control). Those assigned to the intervention group had triage
      nurses applying the OAR, and those with positive OAR were sent for roentgenograms
      before physician evaluation. Physicians were blinded to negative OAR nurse
      assessments. Investigators were blinded to group allocation. The primary outcome
      was the total mean length of stay (TLOS). The secondary outcomes were patient
      satisfaction (five-point ordinal scale) and the proportion willing to return to
      the site for future care. Two-independent sample t-test was used to analyze the
      TLOS. The Kruskal-Wallis test was used to analyze satisfaction ratings
      differences between groups. Fisher's exact test was used to analyze the willing
      to-return outcome. This study had 80% power to detect an effect size of 25
      minutes. RESULTS: Two hundred thirty-two patients were eligible; 130 patients
      gave consent and were enrolled. Three patients were then excluded, three were
      lost to follow-up, and one left without being seen. The intervention and control
      groups had mean TLOS of 73.0 minutes and 79.7 minutes, respectively. There was a
      statistically nonsignificant time difference of -6.7 minutes (95% CI = -20.9 to
      7.4) between groups. There were no differences in patient satisfaction ratings (p
      value = 0.343) or WOR (3.8%; 95% CI = -3.3% to 11.0%). CONCLUSIONS: The use of
      OAR and the ordering of roentgenograms by triage nurses before physician
      evaluation for twisting ankle or foot injuries does not decrease the length of
      stay in an urgent care department.

PMID- 16436791
TI  - The effect of Picture Archiving and Communications Systems on the accuracy of
      diagnostic interpretation of pediatric emergency physicians.
AB  - OBJECTIVES: To compare the accuracy of diagnostic interpretation of radiographs
      by pediatric emergency physicians (EPs) before and after the introduction of a
      Picture Archiving and Communications System (PACS). METHODS: The pre-PACS study
      period included results from September 2001, when patients were evaluated by
      using only conventional radiographs. The post-PACS study period consisted of
      results from September 2002, when patients were evaluated by using only digital
      radiographic studies. During these periods, consecutive medical records of all
      patients who underwent radiological studies when attending the pediatric
      emergency department (ED) were reviewed. The radiographic interpretation by the
      pediatric EP, documented at the time of the ED visit, was compared with that made
      by the pediatric radiologist. RESULTS: Data were available from 1,644/1,651 sets
      of conventional radiographs ordered for the pre-PACS study period and from
      1,430/1,431 sets of digital radiographic studies for the post-PACS study period.
      The prevalence of positive radiological studies as per the radiologists was 32.2%
      (pre-PACS study period) vs. 28.7% (post-PACS study period). Diagnostic
      performance of the pediatric EPs for the two time periods was as follows: overall
      accuracy, 98.1% (95% confidence interval [CI] = 94.5% to 100%) vs. 98.5% (95% CI
      = 87.5% to 100%); sensitivity, 96.4% (95% CI = 94.5% to 97.8%) vs. 98.1% (95% CI
      = 96.2% to 99.2%); specificity, 98.9% (95% CI = 98.1% to 99.4%) vs. 98.6% (95% CI
      = 97.7% to 99.3%); negative predictive value, 98.3% (95% CI = 97.4% to 99.0%) vs.
      99.2% (95% CI = 98.5% to 99.7%); and positive predictive value, 97.7% (95% CI =
      96.0% to 98.8%) vs. 96.6% (95% CI = 94.4% to 98.2%). The proportion of false
      negatives (FN) was 1.2% (19/1,644) vs. 0.6% (8/1,430). Only one FN patient for
      each time period required immediate follow-up for a missed diagnosis.
      CONCLUSIONS: Radiograph interpretations by pediatric EPs with digital studies
      remain as accurate in comparison with assessments performed by using conventional
      radiographs.

PMID- 16436792
TI  - Physician variability in history taking when evaluating patients presenting with
      chest pain in the emergency department.
AB  - OBJECTIVES: The goal of this study was to examine how physicians in the emergency
      department ask questions of patients presenting with chest pain and whether this
      varies by patient demographics. METHODS: This was a cross-sectional study with
      convenience sampling. A survey was administered to adult emergency department
      patients presenting with chest pain after emergency physicians obtained the
      history and performed the physical examination. No identifying data were
      collected from the patients. In addition to demographics, patients were asked
      whether or not their physician asked them about factors related to coronary
      syndrome and myocardial infarction etiology. RESULTS: A total of 308 of 332
      patients (93%) participated. Patients had a mean age of 52 years, 54% were male,
      and 85% spoke English; classification by race was 31% African American, 28%
      white, 19% Hispanic, and 13% other. History taking did not differ by gender.
      Patients who reported being asked about the following were statistically
      significantly younger than those who reported not being asked: family history,
      other medical problems, smoking, cocaine use, and alcohol use. Nonwhite patients
      reported being asked about the following more frequently than white patients:
      smoking (94% vs. 84%), alcohol use (81% vs. 70%), and cocaine use (64% vs. 42%).
      In multivariate logistic regression controlling for age, nonwhite patients were
      more likely than white patients to be asked about smoking (odds ratio [OR], 2.79;
      95% confidence interval [CI] = 1.26 to 6.19), cocaine use (OR, 2.49; 95% CI =
      1.50 to 4.12), and alcohol use (OR, 1.77; 95% CI = 1.0 to 3.09). CONCLUSIONS: The
      variability in questions about behavioral factors associated with chest pain
      etiology as reported by patients may indicate a possible cultural bias by
      physicians. Differences in risk identification may lead to differences in
      treatment decisions.

PMID- 16436793
TI  - Patient and physician perceptions as risk factors for oligoanalgesia: a
      prospective observational study of the relief of pain in the emergency
      department.
AB  - OBJECTIVES: Previous studies have reported that pain is undertreated in the
      emergency department (ED), but few physician-dependent risk factors have been
      identified. In this study, the authors determine whether pain treatment and
      relief in ED patients are negatively associated with the physician's perception
      of whether the patient was exaggerating symptoms, and with the patient and
      physician's perceptions of the interaction between them, as well as whether
      demographic characteristics were associated with these perceptions. METHODS: This
      was a prospective observational study of patients who were undergoing treatment
      for painful disorders in the ED. Before treatment for pain, patients were asked
      to complete a 100-mm visual analog scale (VAS) describing their pain. Demographic
      information and pain treatments administered were recorded. Patients completed a
      second pain VAS before discharge from the ED. Patients were then asked to
      complete three queries describing their perception of their interaction with the
      physician. After the patient had left the department, the patient's physician was
      asked to complete a query describing his or her perception of the interaction and
      to complete a VAS describing how likely it was that the patient was exaggerating
      symptoms to obtain pain medicines for nonmedical purposes. RESULTS: There were
      1,695 patients enrolled in the study; 32 patients were excluded because of
      missing or incomplete data, leaving 1,663 for analysis. Of these patients, 71.9%
      received a pain medication while in the ED. There was no association between the
      physician's VAS for perceived exaggeration of symptoms, the queries describing
      physician-patient interactions, and patient ethnicity and whether patients
      received pain treatment in the ED. There was a negative correlation between the
      physician's VAS for perceived exaggeration of symptoms and the change in the
      patient's pre- and posttreatment pain VAS scores. The physician's VAS score for
      perceived exaggeration of symptoms was higher among Native American patients than
      among other ethnic groups (p < or = 0.001). The patient and physician queries
      rating their interaction show a decreased absolute reduction of VAS pain scores
      (p > or = 0.001) and a reduction in the number of patients having at least a 50%
      reduction in their pain VAS score when interactions were rated "bad" and "very
      bad" (p < or = 0.001). CONCLUSIONS: The physician's perception of whether a
      patient was exaggerating symptoms was associated with the patient's ethnic
      background and with both the physician's and patient's perception of their
      interaction. These perceptions were negatively associated with the achievement of
      pain relief and the change in the patient's pain VAS scores, but not with whether
      a patient was treated with a pain medication.

PMID- 16436794
TI  - Decreased mortality by normalizing blood glucose after acute ischemic stroke.
AB  - OBJECTIVES: Hyperglycemia after cerebral ischemia exacerbates brain injury and
      worsens the outcome of stroke patients. The authors sought to examine the effect
      of glycemic control on mortality after acute stroke. METHODS: This was a
      retrospective study of patients discharged with a diagnosis of ischemic stroke
      during a 40-month period from a large urban U.S. health system. Patients were
      compared by initial blood glucose (BG) levels and by glycemic control during the
      first 48 hours of hospitalization. RESULTS: Of 960 patients with thromboembolic
      stroke, 373 (38.9%) were hyperglycemic (BG > or = 130 mg/dL) on hospital
      admission. Admission hyperglycemia was associated with a higher mortality rate
      than was euglycemia (odds ratio [OR] = 3.15; 95% confidence interval [CI] = 1.45
      to 6.85; p = 0.004). Persistent hyperglycemia (PerHyp) during 48 hours of
      hospitalization was associated with even higher mortality rate (unadjusted
      logistic regression, OR = 6.54; 95% CI = 2.41 to 17.87; p < 0.001). Glycemic
      control (normalization of BG to < 130 mg/dL) was associated with a 4.6-fold
      decrease in mortality risk as compared with the case of patients with PerHyp (p <
      0.001). Multiple logistic regression showed glycemic control to be a strong
      independent determinant of survival (OR = 5.95; 95% CI = 1.24 to 28.6; p = 0.026)
      after acute stroke even after adjustment for age, gender, concomitant
      hypertension and diabetes, and stroke severity. CONCLUSIONS: Admission
      hyperglycemia is associated with a worse outcome after stroke than is euglycemia.
      Normalization of blood glucose during the first 48 hours of hospitalization
      appears to confer a potent survival benefit in patients with thromboembolic
      stroke.

PMID- 16436795
TI  - Characteristics of emergency medicine program directors.
AB  - OBJECTIVES: To characterize emergency medicine (EM) program directors (PDs) and
      compare the data, where possible, with those from other related published
      studies. METHODS: An online survey was e-mailed in 2002 to all EM PDs of programs
      that were approved by the Accreditation Council of Graduate Medical Education.
      The survey included questions concerning demographics, work hours, support staff,
      potential problems and solutions, salary and expenses, and satisfaction. RESULTS:
      One hundred nine of 124 (88%) PDs (69.7% university, 27.5% community, and 2.8%
      military) completed the survey; 85.3% were male. Mean age was 43.6 years (95%
      confidence interval [CI] = 42.6 to 44.7 yr). The mean time as a PD was 5.7 years
      (95% CI = 4.9 to 6.5 yr), with 56% serving five years or less. The mean time
      expected to remain as PD is an additional 6.0 years (95% CI = 5.2 to 6.8). A 1995
      study noted that 50% of EM PDs had been in the position for less than three
      years, and 68% anticipated continuing in their position for less than five years.
      On a scale of 1 to 10 (with 10 as highest), the mean satisfaction with the
      position of PD was 8.0 (95% CI = 7.2 to 8.3). Those PDs who stated that the
      previous PD had mentored them planned to stay a mean of 2.0 years longer than did
      those who were not mentored (95% CI of difference of means = 0.53 to 3.53). Sixty
      five percent of PDs had served previously as an associate PD. Most PDs (92%) have
      an associate or assistant PD, with 54% reporting one; 25%, two; and 9%, three
      associate or assistant PDs. A 1995 study noted that 62% had an associate PD.
      Ninety-two percent have a program coordinator, and 35% stated that they have both
      a residency secretary and a program coordinator. Program directors worked a
      median of 195 hours per month: clinical, 75 hours; scholarly activity, 20 hours;
      administrative, 80 hours; and teaching and residency conferences, 20 hours;
      compared with a median total hours of 220 previously reported. Lack of adequate
      time to do the job required, career needs interfering with family needs, and lack
      of adequate faculty help with residency matters were identified as the most
      important problems (means of 3.5 [95% CI = 3.2 to 3.7], 3.4 [95% CI = 3.2 to
      3.6], and 3.1 [95% CI = 2.9 to 3.3], respectively, on a scale of 1 to 5, with 5
      as maximum). This study identified multiple resources that were found to be
      useful by >50% of PDs, including national meetings, lectures, advice from others,
      and self-study. CONCLUSIONS: Emergency medicine PDs generally are very satisfied
      with the position of PD, perhaps because of increased support and resources.
      Although PD turnover remains an issue, PDs intend to remain in the position for a
      longer period of time than noted before this study. This may reflect the overall
      satisfaction with the position as well as the increased resources and support now
      available to the PD. PDs have greater satisfaction if they have been mentored for
      the position.

PMID- 16436796
TI  - Cognitive performance following modafinil versus placebo in sleep-deprived
      emergency physicians: a double-blind randomized crossover study.
AB  - OBJECTIVES: Modafinil has recently been approved for the treatment of shift work
      sleep disorder, making it potentially available for shift-working emergency
      physicians. The authors' objectives were to determine whether modafinil improved
      cognitive performance of emergency physicians following overnight shifts and to
      record symptoms and subjective evaluations of the effect of modafinil on the
      participants. METHODS: This was a randomized, double-blind, placebo-controlled
      crossover study that followed CONSORT guidelines. Participants were assigned to
      one of two study groups, with study sessions occurring at least seven weeks
      apart, and received either modafinil or placebo depending on their random
      allocation. Testing after night shifts included a coding task and an AX version
      of the Continuous Performance Task, both of which test cognitive function.
      Participants also completed visual analog scales for three subjective outcomes,
      and symptoms were elicited. RESULTS: Modafinil facilitated performance on long
      interstimulus-interval AX trials (F [1, 23] = 6.65, p = 0.1) and marginally
      reduced errors on AY trials in the Continuous Performance Task (F [1, 23] = 3.59,
      p = 0.07), suggesting facilitation of sustained attention, cognitive control, and
      working memory. Additionally, modafinil, compared with placebo, facilitated
      performance on the coding task at the first session. Subjective data from visual
      analog scales confirmed that modafinil increased perceived alertness during the
      simulated patient care sessions but worsened sleep onset when opportunities for
      sleep arose. CONCLUSIONS: Modafinil increased certain aspects of cognitive
      function and subjectively improved participants' ability to attend post-night
      shift didactic sessions but made it more difficult for participants to fall
      asleep when opportunities for sleep arose.

PMID- 16436797
TI  - Intralipid prolongs survival in a rat model of verapamil toxicity.
AB  - OBJECTIVES: Verapamil is a lipid-soluble calcium channel blocker with significant
      mortality in overdose. Previous investigators have demonstrated the benefit of
      lipid emulsion therapy in ameliorating toxicity from lipid-soluble agents. The
      authors investigated the effect of Intralipid treatment in a rat model of
      verapamil toxicity. METHODS: Thirty sedated Wistar rats were infused with
      verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, animals were
      treated with a bolus of either 12.4 mL/kg 20% Intralipid or 12.4 mL/kg 0.9%
      saline. Verapamil infusion was continued until the animals were killed.
      Respiratory rate, heart rate, and electrocardiography were sampled every 2.5
      minutes throughout. RESULTS: Survival was prolonged in the Intralipid-treated
      group (44 +/- 21 vs. 24 +/- 9 minutes; p = 0.003). The median lethal dose was
      increased in the Intralipid group (25.7 mg/kg [95% confidence interval {CI} =
      24.7 to 26.7] vs. 13.6 mg/kg [95% CI = 12.2 to 15.0]). A less marked decrease in
      heart rate was observed during verapamil infusion in the Intralipid-treated group
      (6.8 beats/min [95% CI = 8.3 to 5.2] for Intralipid vs. 10.7 beats/min [95% CI =
      12.6 to 8.9] for saline; p = 0.001). CONCLUSIONS: Intralipid treatment prolongs
      survival and doubles median lethal dose in a rat model of verapamil toxicity. The
      mechanism of action remains to be elucidated.

PMID- 16436798
TI  - Emergency department visits for sledding injuries in children in the United
      States in 2001/2002.
AB  - OBJECTIVES: To describe the characteristics of nonfatal sledding-related injuries
      in U.S. children resulting in emergency department (ED) visits in 2001/2002 and
      to explore the implications of these findings for injury prevention efforts.
      METHODS: A stratified probability sample of U.S. hospitals providing emergency
      services in the National Electronic Injury Surveillance System-All Injury Program
      was utilized for 2001/2002. ED visits resulting from injuries involving sleds,
      snow discs, snow tubes, and toboggans were analyzed for patients 19 years of age
      or younger. RESULTS: In 2001/2002, there were an estimated 57,866 ED visits for
      sledding-related injuries in the United States for all age groups. Of these,
      41,272 (71%) occurred in patients 19 years of age or younger, 58% of whom were
      male. The highest number of injuries occurred in children between five and 14
      years of age (74%), and the injuries were most often caused by falls or
      collisions (75%). The head or neck was the most frequently injured body region
      among those 0-9 years of age, while the extremities were injured most commonly
      among those 10-19 years of age. Head and neck injuries occurred in 56% (95%
      confidence interval [CI] = 32% to 81%) of children 0-4 years of age versus 19%
      (95% CI = 9% to 29%) of patients 15-19 years of age. Nine percent (95% CI = 6% to
      12%) of patients sustained a traumatic brain injury. Three percent (95% CI = 1%
      to 5%) of patients required admission to the hospital. CONCLUSIONS: Sledding
      injuries resulting in ED visits predominantly affect children and are a source of
      measurable morbidity in this population. An increase in injury prevention efforts
      for this activity is warranted.

PMID- 16436799
TI  - Surging to the right standard of care.

PMID- 16436802
TI  - Science to practice: do mural attenuation and thickness at contrast-enhanced CT
      enterography correlate with endoscopic and histologic findings of inflammation in
      Crohn disease?
AB  - SUMMARY: Endoscopy is frequently used as the reference standard in the evaluation
      of inflammation. However, endoscopy enables visualization of the mucosa only, has
      a limited reach, and has difficulty in anatomic orientation. Therefore, it is not
      a stand-alone diagnostic procedure. Imaging is needed if one is to visualize the
      entire intestinal wall, define the extent of disease, and categorize disease
      subtypes. Bodily et al in this issue of Radiology have described an objective,
      more reliable, and hopefully reproducible method of measuring active inflammation
      of a segment of bowel by quantifying mural enhancement in patients examined with
      CT enterography. Their results showed good correlation with ileoscopic and
      histologic findings of active inflammation.

PMID- 16436803
TI  - Medical professionalism in the new millennium: a physicians' charter.

PMID- 16436801
TI  - Hierarchical clustering algorithm for comprehensive orthologous-domain
      classification in multiple genomes.
AB  - Ortholog identification is a crucial first step in comparative genomics. Here, we
      present a rapid method of ortholog grouping which is effective enough to allow
      the comparison of many genomes simultaneously. The method takes as input all
      against-all similarity data and classifies genes based on the traditional
      hierarchical clustering algorithm UPGMA. In the course of clustering, the method
      detects domain fusion or fission events, and splits clusters into domains if
      required. The subsequent procedure splits the resulting trees such that intra
      species paralogous genes are divided into different groups so as to create
      plausible orthologous groups. As a result, the procedure can split genes into the
      domains minimally required for ortholog grouping. The procedure, named DomClust,
      was tested using the COG database as a reference. When comparing several
      clustering algorithms combined with the conventional bidirectional best-hit (BBH)
      criterion, we found that our method generally showed better agreement with the
      COG classification. By comparing the clustering results generated from datasets
      of different releases, we also found that our method showed relatively good
      stability in comparison to the BBH-based methods.

PMID- 16436800
TI  - Experimental approaches to identify non-coding RNAs.
AB  - Cellular RNAs that do not function as messenger RNAs (mRNAs), transfer RNAs
      (tRNAs) or ribosomal RNAs (rRNAs) comprise a diverse class of molecules that are
      commonly referred to as non-protein-coding RNAs (ncRNAs). These molecules have
      been known for quite a while, but their importance was not fully appreciated
      until recent genome-wide searches discovered thousands of these molecules and
      their genes in a variety of model organisms. Some of these screens were based on
      biocomputational prediction of ncRNA candidates within entire genomes of model
      organisms. Alternatively, direct biochemical isolation of expressed ncRNAs from
      cells, tissues or entire organisms has been shown to be a powerful approach to
      identify ncRNAs both at the level of individual molecules and at a global scale.
      In this review, we will survey several such wet-lab strategies, i.e. direct
      sequencing of ncRNAs, shotgun cloning of small-sized ncRNAs (cDNA libraries),
      microarray analysis and genomic SELEX to identify novel ncRNAs, and discuss the
      advantages and limits of these approaches.

PMID- 16436805
TI  - An opportunity for radiology.

PMID- 16436806
TI  - Lung cancer screening: radiology's opportunity here and now.

PMID- 16436807
TI  - Assessing the efficacy of lung cancer screening.

PMID- 16436808
TI  - Biomedical Imaging Research Opportunities Workshop III: summary of findings and
      recommendations.

PMID- 16436809
TI  - Integrated PET/CT: current applications and future directions.
AB  - For the past 5 years, combined positron emission tomography (PET) and computed
      tomography (CT), or PET/CT, has grown because the PET portion provides
      information that is very different from that obtainable with other imaging
      modalities. However, the paucity of anatomic landmarks on PET images makes a
      consistent "hardware fusion" to anatomic cross-sectional data extremely useful.
      Clinical experience indicates a single direction: Addition of CT to PET improves
      specificity foremost, but also sensitivity, and the addition of PET to CT adds
      sensitivity and specificity in tumor imaging. Thus, PET/CT is a more accurate
      test than either of its individual components and is probably also better than
      side-by-side viewing of images from both modalities. The synergistic advantage of
      adding CT is that the attenuation correction needed for PET can also be derived
      from the CT data, an advantage not obtainable by integrating PET and magnetic
      resonance imaging. This makes PET/CT 25%-30% faster than PET alone with standard
      attenuation-correction methods, leading to higher patient throughput and a more
      comfortable examination, which typically last 30 minutes or less.
      Fluorodeoxyglucose (FDG) PET/CT appears to provide relevant information in the
      staging and therapy monitoring of many tumors, including lung carcinoma,
      mesothelioma, colorectal cancer, lymphoma, melanoma, and many others, with the
      notable exception of prostatic cancer. For prostatic cancer, choline derivatives
      may become useful radiopharmaceuticals. The published literature on the
      applications of FDG PET/CT in oncology is still limited, but several well
      designed studies have demonstrated the benefits of PET/CT.

PMID- 16436810
TI  - Breast lesions: evaluation with US strain imaging--clinical experience of
      multiple observers.
AB  - PURPOSE: To prospectively determine the accuracy of using an ultrasonographic
      (US) strain imaging technique known as lesion size comparison to differentiate
      benign from malignant breast lesions. MATERIALS AND METHODS: Institutional Review
      Board approval and patient informed consent were obtained for this HIPPA
      compliant study. US strain imaging was performed prospectively for 89 breast
      lesions in 88 patients. Lesions were imaged by using freehand compression and a
      real-time strain imaging algorithm. Five observers obtained manual measurements
      of lesion height, width, and area from B-mode and strain images. By using these
      size measurements, individual observer and group performances were assessed by
      using the area under the receiver operating characteristic curve (A(z)). The
      performance of a single size parameter versus that of a combination of size
      parameters was evaluated by using univariate and multivariate logistic
      regression. RESULTS: Group A(z) values showed that width ratio and area ratio
      yielded the best results for differentiating benign and malignant breast lesions,
      and they were not statistically different from one another (P = .499). For the
      group, the performance of area and width, which was superior to that of height
      and aspect ratio, was statistically significant for all cases (P < .011) except
      for those that compared area with aspect ratio (P = .118). By using a group
      threshold of 1.04 for width ratio and 1.13 for area ratio, the sensitivity and
      specificity of the technique were 96% and 21%, respectively, for width and 96%
      and 24%, respectively, for area. The best observer achieved a sensitivity of 96%
      and a specificity of 61% by using the area ratio. For all but one observer,
      combined size parameters did not improve observer performance (P > .258).
      Significant interobserver performance variability was observed (P < .001).
      CONCLUSION: Results suggest that US strain imaging has the potential to aid
      diagnosis of breast lesions. However, manually tracing lesion boundaries for size
      ratio differentiation in a busy clinical setting did not match the diagnostic
      performance levels previously reported. Focusing on measurements of lesion width,
      along with additional observer training or automated processes, may yield a
      suitable method for routine clinical application.

PMID- 16436811
TI  - Correlation of radiologist rank as a measure of skill in screening and diagnostic
      interpretation of mammograms.
AB  - PURPOSE: To determine whether skill in the interpretation of screening mammograms
      is correlated with skill in the interpretation of diagnostic mammograms.
      MATERIALS AND METHODS: The institutional review board of the University of South
      Florida approved this study. This study was determined to be exempt from informed
      consent requirements because of the retrospective use of images and was conducted
      before HIPPA requirements were implemented. A total of 59 radiologists
      interpreted screening and diagnostic performance test sets of mammograms with a 1
      year interval. Interpretations were recorded with modifications of the Breast
      Imaging and Reporting Data System. Radiologist skill was measured as the
      radiologist's ranking among his or her cohort in each of several measures of
      performance (ie, performance test receiver operating characteristic curve area,
      performance test screening sensitivity, performance test diagnostic sensitivity,
      and associated specificities). Correlations between radiologist rank in screening
      and rank in the diagnostic performance test measures were analyzed with the
      Spearman rank correlation statistical test. RESULTS: Radiologist rank in
      screening interpretations and in diagnostic interpretations was found to be
      significantly correlated in all measurements (P < .05). However, only two
      measurments (ie, receiver operating characteristic curve area rank correlation of
      0.327 and sensitivity rank correlation of 0.402) remained significant after
      adjusting for multiple testing. The correlation between ranked screening
      specificity and ranked diagnostic specificity (0.296) was significant at only the
      .05 level. CONCLUSION: The interpretive performance of radiologists among their
      peers is moderately correlated between screening and diagnostic interpretations.
      Thus, proficiency in one area does not guarantee proficiency in the other area
      for some radiologists.

PMID- 16436812
TI  - Blunt abdominal trauma: utility of 5-minute delayed CT with a reduced radiation
      dose.
AB  - PURPOSE: To retrospectively evaluate the utility of 5-minute delayed computed
      tomography (CT) of the abdomen and pelvis by using a reduced radiation dose in
      patients with blunt abdominal trauma. MATERIALS AND METHODS: Institutional review
      board consent was obtained, and written informed consent was waived. The study
      was HIPAA compliant. A total of 662 patients (497 men, 165 women; mean age, 40.5
      years; range, 18-94 years) were identified who were evaluated with CT after blunt
      abdominal trauma during a 1-year period. Delayed CT scans were acquired 5 minutes
      after intravenous contrast material injection by using a decreased tube current
      of 100 mAs. Injury was identified in 106 patients. Two radiologists blinded to
      initial CT scan interpretation reviewed these cases to determine the quality and
      utility of delayed scans. Disagreement was settled by consensus. Delayed scans
      were considered useful when they aided in (a) characterizing initial CT findings,
      (b) identifying findings not present at initial CT, (c) excluding injury
      suggested at initial CT, and (d) increasing reader confidence with regard to
      initial CT findings. RESULTS: All delayed scans were diagnostic. Delayed scans
      were useful in 27% (12 of 44) of patients with solid organ injury, 5.9% (one of
      17) of patients with bowel or mesenteric injury, 4.5% (one of 22) of patients
      with pelvic fractures, and in none of the patients with free fluid only. Overall,
      delayed CT was useful in 2.1% (14 of 662) of all patients (95% confidence
      interval: 1.0, 3.2) referred for evaluation following blunt abdominal trauma.
      Utility increased to 13.2% (14 of 106) (95% confidence interval: 6.8, 19.7) in
      the group of patients with injury or suspected of having injury after initial CT.
      CONCLUSION: If delayed CT scans are acquired when patients with blunt abdominal
      trauma are evaluated, selective, rather than routine, acquisition is recommended
      and a reduced radiation dose seems adequate.

PMID- 16436813
TI  - MR imaging- versus conventional X-ray fluoroscopy-guided renal angioplasty in
      swine: prospective randomized comparison.
AB  - PURPOSE: To test the hypothesis that the technical success rates, complication
      rates, and procedural times for magnetic resonance (MR) imaging-guided
      percutaneous transluminal angioplasty (PTA) and conventional (x-ray) fluoroscopy
      guided PTA for treatment of renal artery stenosis are similar. MATERIALS AND
      METHODS: The study was animal care and use committee approved. After surgically
      inducing bilateral renal artery stenosis in 11 swine, the authors performed
      baseline digital subtraction angiography. They transferred each animal to a 1.5-T
      MR imaging unit and randomly decided which artery would be treated with MR-guided
      PTA. With MR imaging guidance, angioplastic devices were tracked by using active
      and passive techniques. Vascular depiction was achieved by using catheter
      directed MR angiography. Stenotic vessels were dilated by using 5-6-mm-diameter
      balloon catheters. PTA was then performed in the contralateral artery by using
      conventional fluoroscopy-guided techniques. With the intention to treat, the
      authors compared the technical success (residual stenosis < 50%) rates,
      complication rates, and procedural times for each guidance method. They compared
      technical successes and complications by using the McNemar test and procedural
      times by using a paired t test, with P < .05 indicating a significant difference.
      RESULTS: The authors successfully dilated nine (82%) of 11 renal arteries with MR
      guidance and all 11 arteries (100%) with conventional fluoroscopic guidance. The
      difference was not significant (P = .5). Complications occurred in three (27%)
      arteries with MR guidance and in one (9%) artery with fluoroscopic guidance, with
      no significant differences (P = .5). The mean MR-guided PTA procedural time was
      46 minutes longer than the fluoroscopy-guided PTA procedural time; this
      difference was significant (P = .01). CONCLUSION: In a small cohort of swine, the
      authors did not observe a significant difference between MR imaging- and
      conventional fluoroscopy-guided renal artery PTA in terms of success and
      complication rates. However, no evidence of similarity between the techniques
      should be assumed. Procedural times differed significantly.

PMID- 16436814
TI  - An augmented reality system for MR image-guided needle biopsy: initial results in
      a swine model.
AB  - PURPOSE: To evaluate an augmented reality (AR) system in combination with a 1.5-T
      closed-bore magnetic resonance (MR) imager as a navigation tool for needle
      biopsies. MATERIALS AND METHODS: The experimental protocol had institutional
      animal care and use committee approval. Seventy biopsies were performed in
      phantoms by using 20 tube targets, each with a diameter of 6 mm, and 50 virtual
      targets. The position of the needle tip in AR and MR space was compared in
      multiple imaging planes, and virtual and real needle tip localization errors were
      calculated. Ten AR-guided biopsies were performed in three pigs, and the duration
      of each procedure was determined. After successful puncture, the distance to the
      target was measured on MR images. The confidence limits for the achieved in-plane
      hit rate and for lateral deviation were calculated. A repeated measures analysis
      of variance was used to determine whether the placement error in a particular
      dimension (x, y, or z) differed from the others. RESULTS: For the 50 virtual
      targets, a mean error of 1.1 mm +/- 0.5 (standard deviation) was calculated. A
      repeated measures analysis of variance indicated no statistically significant
      difference (P > .99) in the errors in any particular orientation. For the real
      targets, all punctures were inside the 6-mm-diameter tube in the transverse
      plane. The needle depth was within the target plane in 11 biopsy procedures; the
      mean distance to the center of the target was 2.55 mm (95% confidence interval:
      1.77 mm, 3.34 mm). For nine biopsy procedures, the needle tip was outside the
      target plane, with a mean distance to the edge of the target plane of 1.5 mm
      (range, 0.07-3.46 mm). In the animal experiments, the puncture was successful in
      all 10 cases, with a mean target-needle distance of 9.6 mm +/- 4.85. The average
      procedure time was 18 minutes per puncture. CONCLUSION: Biopsy procedures
      performed with a combination of a closed-bore MR system and an AR system are
      feasible and accurate.

PMID- 16436815
TI  - Crohn Disease: mural attenuation and thickness at contrast-enhanced CT
      Enterography--correlation with endoscopic and histologic findings of
      inflammation.
AB  - PURPOSE: To determine retrospectively if quantitative measures of small-bowel
      mural attenuation and thickness at computed tomographic (CT) enterography
      correlate with endoscopic and histologic findings of small-bowel inflammation and
      to estimate the performance of these measures in predicting inflammatory Crohn
      disease. MATERIALS AND METHODS: The institutional review board approved this
      HIPAA-compliant retrospective study, which was conducted with patient informed
      consent. CT enterography data in 96 patients (31 male patients and 65 female
      patients) who underwent ileoscopy with or without biopsy were examined for CT
      signs of active Crohn disease. The most highly enhancing segment of terminal
      ileum and a normal-appearing ileal loop were identified. After it was confirmed
      that semiautomated software could accurately measure mural attenuation and
      thickness, the selected terminal ileal and normal-appearing (control) ileal loops
      were examined (20 automated measurements at each location) to quantify mural
      attenuation and wall thickness. Results were compared with endoscopy and
      histology reports by using logistic regression analysis and receiver operating
      characteristic curves. RESULTS: Quantitative measures of terminal ileal mural
      attenuation and wall thickness correlated significantly with active Crohn disease
      (P < .001). Small-bowel wall thickness was not a significant factor after
      attenuation was taken into account. A threshold attenuation value with a
      sensitivity of 90% (18 of 20) for definite Crohn disease (compared with a
      sensitivity of 80% [16 of 20] for radiologist assessment) was selected. In
      patients who underwent ileal biopsy, threshold attenuation had a sensitivity
      identical to that of ileoscopy (81% [26 of 32]; 95% confidence interval: 64%,
      93%) in predicting histologic inflammation. CONCLUSION: Quantitative measures of
      mural attenuation and wall thickness at CT enterography correlate highly with
      ileoscopic and histologic findings of inflammatory Crohn disease. Quantitative
      measures of mural attenuation are sensitive markers of small bowel inflammation.

PMID- 16436816
TI  - Three-dimensional fast-recovery fast spin-echo MRCP: comparison with two
      dimensional single-shot fast spin-echo techniques.
AB  - PURPOSE: To retrospectively evaluate the technical quality of and the visibility
      of the biliary tree and pancreatic duct on magnetic resonance (MR)
      cholangiopancreatographic (MRCP) images obtained with a single-breath-hold three
      dimensional (3D) fast-recovery fast spin-echo (FRFSE) sequence in comparison with
      conventional two-dimensional (2D) single-shot fast spin-echo (SSFSE) thin-section
      and thick-slab sequences. MATERIALS AND METHODS: Institutional review board
      approval was obtained; informed consent was not required for this HIPAA-compliant
      study. MRCP was performed at 1.5 T in 53 consecutive patients (25 men and 28
      women, aged 23-84 years). A single-breath-hold volume acquisition was performed
      by using the 3D FRFSE sequence and the conventional 2D SSFSE sequences. Two
      radiologists graded studies obtained with each sequence in a blinded fashion, and
      the paired Student t test was used to assess differences in technical quality,
      visibility of eight individual ductal segments of the biliary tree and pancreatic
      duct, and number of ductal segments visualized per patient. RESULTS: Studies
      obtained with 3D FRFSE were of significantly higher technical quality than those
      obtained with thin-section 2D SSFSE (P < .02 for both readers). The 3D FRFSE
      maximum intensity projection reconstruction and 2D SSFSE thick-slab sequence
      proved statistically equivalent with regard to the overall visibility of the
      biliary tree and pancreatic duct and the number of ductal segments visualized per
      patient. In comparison with 2D SSFSE thin-section imaging, however, 3D FRFSE
      imaging produced an improved overall duct segment visibility grade of 0.45 on a
      three-point visibility scale (P < .001), with a corresponding average per-patient
      improvement of 1.9 out of eight possible fully visualized duct segments (P <
      .001). CONCLUSION: The 3D FRFSE sequence shows promise for improved visibility of
      the pancreatic duct and biliary tree, compared with the conventional 2D SSFSE
      thin-section and thick-slab approach, while permitting the entire MRCP
      examination to be performed in a single breath hold.

PMID- 16436817
TI  - Intraductal papillary mucinous neoplasm of pancreas: multi-detector row CT with
      2D curved reformations--correlation with MRCP.
AB  - PURPOSE: To retrospectively compare accuracy of multi-detector row computed
      tomography (CT), combined with two-dimensional (2D) curved reformations, and that
      of magnetic resonance (MR) cholangiopancreatography (MRCP) for characterization
      of intraductal papillary mucinous neoplasm (IPMN) as malignant, with pathologic
      examination as reference standard. MATERIALS AND METHODS: Institutional review
      board approval was obtained, informed consent was waived, and study was HIPAA
      compliant. Twenty-five patients (12 women, 13 men; age range, 44-88 years) with
      pathologically proved IPMN were examined with dual-phase CT with 1.25-mm-thick
      sections for pancreatic phase; 2D curved reformations along main pancreatic duct
      (MPD) were generated. T2-weighted MRCP included thick- and thin-slab single-shot
      fast spin-echo imaging and transverse fast spin-echo imaging. Two radiologists,
      blinded to surgical and pathologic findings, evaluated images for lesion
      location, septa, mural nodules, communication with MPD, extent and diameter of
      MPD dilatation, calcifications, and vascular encasement. Malignancy was suspected
      when one of the following was present: MPD diameter larger than 10 mm, mural
      nodules, vascular encasement, peripancreatic lymphadenopathy, or metastases.
      Sensitivity and specificity values for prediction of malignancy were calculated
      for CT and MRCP. Interobserver variability was determined (kappa analysis).
      RESULTS: Excellent correlation between modalities was observed. Cyst
      communication was seen in 20 and 21 of 24 branch pancreatic duct (BPD) IPMNs with
      CT and MRCP, respectively. Sensitivity, specificity, and accuracy for detection
      of malignancy were 70%, 87%, and 76% (CT) and 70%, 92%, and 80% (MRCP),
      respectively. Interobserver agreement was good to perfect for both readers in all
      comparisons (overall, kappa = 0.70-1.00). CONCLUSION: CT combined with 2D curved
      reformation can provide imaging details of IPMN, including communication of BPD
      IPMN with MPD, that are almost equivalent to those provided at MRCP. Presence of
      mural nodules, dilated MPD (>10-mm diameter), or thick septa at CT or MRCP may be
      used as independent predictors of malignancy.

PMID- 16436818
TI  - Assessment of acute abdominal pain: utility of a second cross-sectional imaging
      examination.
AB  - PURPOSE: To retrospectively determine how often a second cross-sectional imaging
      examination provides useful additional information or alters management of acute
      abdominal pain. MATERIALS AND METHODS: The research ethics board approved this
      study; the informed consent requirement was waived. Authors assessed imaging
      reports and clinical charts of adult patients who presented to the emergency
      department and underwent both computed tomography (CT) and ultrasonography (US)
      of the abdomen within 72 hours. A total of 255 patients fulfilled study criteria.
      The second examination was categorized as providing additional useful
      information, providing no additional useful information, or providing
      contradictory information. It was also noted whether the second examination was
      recommended because of findings of the first and whether the results of the
      second altered clinical management. Follow-up was available in 149 patients, and
      a definitive diagnosis was established. For these patients, it was determined
      whether either examination favored the correct diagnosis. Fisher exact test, one-
      and two-sample tests for equality of proportions with continuity correction, and
      the chi(2) test were used, where appropriate. RESULTS: In 85 patients (33.3%),
      findings of the second examination agreed with those of the first examination and
      provided additional information. In 153 patients (60.0%), findings of the second
      examination agreed with those of the first examination and provided no additional
      information. In 17 patients (6.7%), findings of the second examination were
      contradictory to findings of the first examination. The percentage of follow-up
      CT examinations that provided no additional useful information was significantly
      lower when recommended by the radiologist (38%) than when recommended by someone
      else (72%, P < .001). The percentage of follow-up US examinations that provided
      no additional useful information was significantly lower when recommended by the
      radiologist (42%) than when recommended by someone else (74%, P = .003). In the
      149 patients in whom a final diagnosis was available, both sets of scans were
      correct in 87 patients (58.4%); only the second set of scans was correct in 43
      (28.8%). Overall, findings of the second examination led to a change or could
      have led to a change in treatment of 23 patients (9.0%). CONCLUSION: A second
      examination is significantly more likely to be useful when performed because of
      radiologist recommendation.

PMID- 16436819
TI  - Renal artery stenosis: functional assessment with dynamic MR perfusion
      measurements--feasibility study.
AB  - PURPOSE: To prospectively assess feasibility of renal magnetic resonance (MR)
      perfusion measurement method based on turbo fast low-angle shot sequences for
      grading effect of renal artery stenosis (RAS) on parenchymal perfusion. MATERIALS
      AND METHODS: Institutional review board approved this study, and patients gave
      written consent. Seventy-three patients (34 male, 39 female; age range, 17-84
      years) who were clinically suspected of having RAS underwent contrast material
      enhanced (gadodiamide) saturation-recovery turbo fast low-angle shot imaging for
      measurement of renal perfusion and high-spatial-resolution MR angiography for RAS
      detection and grading. Degree of stenosis was evaluated as high grade (>/=75%
      stenosis), low to intermediate grade (>0% to <75% stenosis), or absent. High
      temporal resolution of the turbo fast low-angle shot sequence allowed acquisition
      of an exact first-pass tracing of the contrast agent bolus from which a signal
      intensity (SI)-time curve was derived. On the basis of this curve, mean transit
      time (MTT) of the contrast agent bolus, maximal upslope (MUS) of the curve,
      maximum SI, and time to SI peak (TTP) were calculated with a gamma variate fit.
      Wilcoxon rank sum test, Pearson product moment correlation, and paired t test
      were used for statistical analysis. RESULTS: Twenty-four renal arteries had high
      grade RAS, 12 renal arteries had low- to intermediate-grade RAS, and 104 renal
      arteries had no RAS. Significant differences between patients without stenoses or
      with low- to intermediate-grade stenoses and patients with high-grade stenoses
      were found for MTT, MUS, and TTP (P < .001). Perfusion parameters were correlated
      with patients' serum creatinine levels, and significant correlations were found
      for MTT (r = 0.41), MUS (r = 0.48), and TTP (r = 0.4), with P < .001. CONCLUSION:
      MR perfusion parameters can be used to assess effect of RAS on parenchymal
      perfusion. Perfusion measurements reflect renal function as measured with serum
      creatinine levels.

PMID- 16436820
TI  - Assessment of vascular invasion by musculoskeletal tumors of the limbs: use of
      contrast-enhanced MR angiography.
AB  - PURPOSE: To prospectively evaluate the accuracy of contrast material-enhanced
      magnetic resonance (MR) angiography in the evaluation of vascular invasion by
      bone and soft-tissue tumors, with surgery serving as the reference standard.
      MATERIALS AND METHODS: This study was approved by the regional ethics committee,
      and all patients gave informed consent. Preoperative MR angiograms and MR images
      of 31 sites in 30 patients with bone or soft-tissue sarcomas (n = 21) or other
      tumors (n = 9) were assessed for features of vascular invasion. All images were
      prospectively evaluated by two musculoskeletal radiologists working in consensus.
      MR images were evaluated for the presence of a fat plane between the vessels and
      the tumor and partial or total encasement of vessels. MR angiograms were
      evaluated for the presence of vascular displacement, stenosis, or occlusion. MR
      imaging and MR angiographic features of vascular invasion were graded. Imaging
      findings were correlated with surgical findings and classified as negative if
      there was no vascular invasion and as positive if there was vascular invasion.
      RESULTS: Among the 31 cases, 20 were classified as negative and 11 were
      classified as positive at surgery. All but three cases with a gap between the
      tumor and the vessels on MR images were classified as free and without adhesions
      at surgery. All cases with arterial stenoses at MR angiography had tumoral
      adhesion or tumoral encasement at surgery. MR imaging had a sensitivity of 64%, a
      specificity of 95%, a positive predictive value of 88% a negative predictive
      value of 83%, and an accuracy of 84% in the detection of vascular invasion on the
      basis of findings of partial or total encasement. MR angiography had a
      sensitivity of 82%, a specificity of 85%, a positive predictive value of 75%, a
      negative predictive value of 90%, and an accuracy of 84% in the detection of
      vascular invasion on the basis of the findings of a stenosis. CONCLUSION: On
      contrast-enhanced MR angiograms, findings of stenosis were sensitive and specific
      in the detection of arterial invasion. MR imaging evidence of partial or total
      encasement is highly specific in the detection of vascular invasion, while MR
      imaging evidence of a gap between the tumor and the vessels excludes an arterial
      invasion.

PMID- 16436821
TI  - Neuropathic arthropathy of the foot with and without superimposed osteomyelitis:
      MR imaging characteristics.
AB  - PURPOSE: To determine retrospectively the magnetic resonance (MR) findings
      associated with pedal neuropathic arthropathy with and without superimposed
      osteomyelitis and to identify any useful discriminating features. MATERIALS AND
      METHODS: Investigational review board approval was obtained and allowed review of
      records and images without informed consent. HIPAA compliance was observed.
      Contrast-enhanced MR images in patients with diabetic neuropathic arthropathy of
      the foot were examined by two reviewers in consensus. Affected joints were
      examined for marrow, articular, periarticular, and soft-tissue findings. Presence
      of superimposed osteomyelitis was documented. A subgroup that had undergone MR
      before infection was evaluated for comparison; chi(2) and t tests were used to
      evaluate the associations. RESULTS: Of 128 neuropathic joints in 63 patients (24
      female, 39 male; aged 31-78 years), 43 had superimposed osteomyelitis. Effusion
      was common in all neuropathic joints, but thin rim enhancement was more common in
      noninfected joints (62% vs 21%, P < .001) and diffuse joint fluid enhancement was
      more common with infection (47% vs 26%, P = .052). Subluxation, bone
      proliferation, fragmentation, and erosion were seen in both groups, but
      intraarticular bodies were more common in noninfected joints (53% vs 12%, P <
      .001). In the periarticular soft tissues, edema, enhancement, and ulceration were
      common in both groups. Fluid collections in the soft tissues were more commonly
      associated with infected joints (95% vs 48%, P < .001) and, when present next to
      an infected joint, were larger than those next to noninfected neuropathic joints
      (2.6 cm(2) [range, 0.3-8.6 cm(2)] vs 1.6 cm(2) [range, 1.0-2.4 cm(2)]). Soft
      tissue fat replacement (68% vs 36%, P = .002) and sinus tracts (84% vs 0%, P <
      .001) were also more common with infection. In the marrow, periarticular signal
      intensity abnormality was common in both groups, but the extent was greater with
      infection. Subchondral cysts were seen almost exclusively in noninfected joints
      (76% vs 2%, P < .001). Similar results were obtained in the subgroup of 21 joints
      (15 patients) with both pre- and postinfection MR images. CONCLUSION: Sinus
      tract, replacement of soft-tissue fat, fluid collection, and extensive marrow
      abnormality are MR imaging features indicating superimposed infection. Thin rim
      enhancement of effusion, presence of subchondral cysts, or intraarticular bodies
      indicate absence of infection.

PMID- 16436822
TI  - Brain mapping of deception and truth telling about an ecologically valid
      situation: functional MR imaging and polygraph investigation--initial experience.
AB  - PURPOSE: To examine the neural correlates during deception and truth telling by
      using a functional magnetic resonance (MR) imaging technique and an ecologically
      valid task and to compare the results with those of a standard polygraph
      examination. MATERIALS AND METHODS: All subjects gave written informed consent
      for this HIPAA-approved study, which was approved by the institutional review
      board of Drexel University. Eleven healthy subjects (five female and six male
      subjects; mean age, 28.9 years) were randomly assigned to the group of guilty
      subjects or the group of nonguilty subjects. Each group consisted of two separate
      functional MR imaging conditions: "lie-only condition" and "truth-only
      condition." The lie-only condition was used to compare brain activity during a
      known lie to control questions and a subjective lie to relevant questions. The
      truth-only condition was used to compare brain activity during a known truthful
      response to control questions and a subjective truthful response to relevant
      questions. Functional MR images were acquired with an echo-planar sequence, and
      statistical analysis was performed. Physiologic responses were measured with a
      standard four-channel polygraph instrument. RESULTS: During the deception
      process, specific areas of the frontal lobe (left medial and left inferior
      frontal lobes), temporal lobe (right hippocampus and right middle temporal
      gyrus), occipital lobe (left lingual gyrus), anterior cingulate, right fusiform
      gyrus, and right sublobar insula were significantly active. During the truth
      telling process, specific areas of the frontal (left subcallosal gyrus or
      lentiform nucleus) and temporal (left inferior temporal gyrus) lobes were
      significantly active. The polygraph examination revealed 92% accuracy in
      deceptive subjects and 70% accuracy in truthful subjects. CONCLUSION: Specific
      areas of the brain involved in deception or truth telling can be depicted with
      functional MR imaging.

PMID- 16436823
TI  - Nerve atrophy in severe trigeminal neuralgia: noninvasive confirmation at MR
      imaging--initial experience.
AB  - PURPOSE: To retrospectively evaluate the size of the trigeminal nerve on magnetic
      resonance (MR) images of patients with unilateral trigeminal neuralgia. MATERIALS
      AND METHODS: Institutional review board approval was obtained and informed
      consent was waived for this HIPAA-compliant study. The sizes of the trigeminal
      nerves in 31 patients (18 men and 13 women; mean age, 68 years; age range, 44-84
      years) with clinically confirmed intractable unilateral trigeminal neuralgia were
      measured before treatment with gamma knife radiosurgery. Images were analyzed
      separately by two neuroradiologists who were blinded to the side of the face with
      symptoms. Coronal projection images were used to determine the diameter and cross
      sectional area of the trigeminal nerves at 5 mm from the entry point of the nerve
      into the pons. Comparisons were made by using a paired t test. Interobserver
      variability was assessed by using the Pearson correlation coefficient. RESULTS:
      The mean diameter of the trigeminal nerve on the symptomatic side was
      significantly smaller than the mean diameter on the asymptomatic side in 30 of 31
      patients (2.11 mm +/- 0.40 [standard deviation] and 2.62 mm +/- 0.56, P < .001,
      95% confidence interval: -0.35, -0.67 mm). The mean cross-sectional area on the
      symptomatic side was significantly smaller than the area on the asymptomatic side
      in 27 of 31 patients (4.50 mm(2) +/- 1.75 and 6.28 mm(2) +/- 2.19, P < .001, 95%
      confidence interval: -2.41, -1.16 mm(2)). CONCLUSION: The results indicate that
      trigeminal nerve atrophy can be depicted noninvasively in patients with
      trigeminal neuralgia.

PMID- 16436824
TI  - Low back pain: prediction of short-term outcome of facet joint injection with
      bone scintigraphy.
AB  - PURPOSE: To prospectively evaluate use of bone scintigraphy with single photon
      emission computed tomography (SPECT) for identification of patients with low back
      pain who would benefit from facet joint injections. MATERIALS AND METHODS: The
      protocol was reviewed and approved by the institutional review board. All
      patients provided informed consent. Forty-seven patients (23 men and 24 women)
      with low back pain, who were scheduled for facet joint injections, were
      prospectively enrolled and randomized into groups A and B (mean ages, 43.3 and
      44.2 years, respectively) with a group A-group B ratio of 2:1. Group A patients
      underwent bone scintigraphy with SPECT prior to injection. Group A patients with
      bone scans positive for facet joint abnormalities received injections at the
      levels where abnormalities were identified on the scan (group A1). Group A
      patients with negative scans (group A2) received injections at the levels that
      were decided as in group B. Group B patients received injections at the levels
      indicated by the referring physician and did not undergo bone scintigraphy. All
      patients completed a pain and function questionnaire before injection and at 1,
      3, and 6 months afterward. The change in the American Academy of Orthopaedic
      Surgeons pain scores after 1, 3, and 6 months compared with baseline scores was
      analyzed with analysis of variance and post hoc Bonferroni multiple-comparison
      tests between groups. Cost analysis was performed. RESULTS: The change in the
      pain score at 1 month was significantly higher (P < .004) in group A1 than it was
      in the other two groups. In group A1, 13 of 15 patients had improvement in pain
      score of greater than 1 standard deviation at 1 month, whereas improvement
      occurred in only two of 16 patients in group A2 and five of 16 patients in group
      B. In patients with positive scans, the number of facets treated with injection
      was decreased from 60, which was the number originally indicated by the referring
      physician, to 27. The Medicare cost was reduced from $2191 per patient to $1865
      with the use of SPECT. CONCLUSION: Bone scintigraphy with SPECT can help identify
      patients with low back pain who would benefit from facet joint injections.

PMID- 16436825
TI  - Evaluation of the acetabular labrum at 3.0-T MR imaging compared with 1.5-T MR
      arthrography: preliminary experience.
AB  - Institutional review board approval and informed consent were obtained for this
      HIPAA-compliant study. The purpose of this study was to prospectively compare
      imaging of the acetabular labrum with 3.0-T magnetic resonance (MR) imaging and
      1.5-T MR arthrography. Eight patients (four male, four female; mean age, 38
      years) with hip pain suspicious for labral disease were examined at both MR
      arthrography and MR imaging. Presence of labral lesions, paralabral cysts,
      articular cartilage lesions, subchondral cysts, osteophytes, and synovial
      herniation pits was recorded. There was arthroscopic correlation of findings in
      five patients. MR imaging depicted four surgically confirmed labral tears that
      were identified at MR arthrography, as well as one that was not visualized at MR
      arthrography. MR imaging helped identify all other pathologic conditions that
      were diagnosed at MR arthrography and helped identify one additional surgically
      confirmed focal articular cartilage lesion. These results provide encouraging
      support for evaluation with 3.0-T MR imaging over 1.5-T MR arthrography.

PMID- 16436826
TI  - Articular cartilage of the knee: evaluation with fluctuating equilibrium MR
      imaging--initial experience in healthy volunteers.
AB  - Institutional review board approval and informed consent were obtained for this
      HIPAA-compliant study, whose purpose was to prospectively compare three magnetic
      resonance (MR) imaging techniques-fluctuating equilibrium, three-dimensional (3D)
      spoiled gradient-recalled acquisition in the steady state (SPGR), and two
      dimensional (2D) fast spin echo (SE)-for evaluating articular cartilage in the
      knee. The study cohort consisted of 10 healthy volunteers (four men, six women;
      age range, 26-42 years). Cartilage signal-to-noise ratio (SNR), SNR efficiency,
      cartilage-fluid contrast-to-noise ratio (CNR), CNR efficiency, image quality,
      cartilage visibility, and fat suppression were compared. Cartilage volume was
      compared for the fluctuating equilibrium and 3D SPGR techniques. Compared with 3D
      SPGR and 2D fast SE, fluctuating equilibrium yielded the highest cartilage SNR
      efficiency and cartilage-fluid CNR efficiency (P < .01 for both). Image quality
      was similar with all sequences. Fluctuating equilibrium imaging yielded higher
      cartilage visibility than did 2D fast SE imaging (P <. 01) but worse fat
      suppression than did 3D SPGR and 2D fast SE imaging (P < .04). Cartilage volume
      measurements with fluctuating equilibrium and 3D SPGR were similar. Fluctuating
      equilibrium MR imaging is a promising method for evaluating articular cartilage
      in the knee.

PMID- 16436828
TI  - Case 91: Tuberculous Epididymo-orchitis.

PMID- 16436829
TI  - The dependent viscera sign.

PMID- 16436830
TI  - MR imaging in primary headaches.

PMID- 16436831
TI  - A 45-second CT perfusion protocol for rectal cancers may not be adequate to infer
      vascular permeability--surface area products.

PMID- 16436832
TI  - Assessing tumor perfusion and treatment response in rectal cancer.

PMID- 16436833
TI  - In vitro cytotoxic effects of iodinated contrast media on a renal tubular cell
      line.

PMID- 16436837
TI  - MAC should stand for Maximum Anesthesia Caution, not Minimal Anesthesiology Care.

PMID- 16436838
TI  - Endotracheal tubes: the conduit for oral and nasal microbial communities to the
      lungs.

PMID- 16436839
TI  - Injury and liability associated with monitored anesthesia care: a closed claims
      analysis.
AB  - BACKGROUND: To assess the patterns of injury and liability associated with
      monitored anesthesia care (MAC) compared with general and regional anesthesia,
      the authors reviewed closed malpractice claims in the American Society of
      Anesthesiologists Closed Claims Database since 1990. METHODS: All surgical
      anesthesia claims associated with MAC (n = 121) were compared with those
      associated with general (n = 1,519) and regional (n = 312) anesthesia. A detailed
      analysis of MAC claims was performed to identify causative mechanisms and
      liability patterns. RESULTS: MAC claims involved older and sicker patients
      compared with general anesthesia claims (P < 0.025), often undergoing elective
      eye surgery (21%) or facial plastic surgery (26%). More than 40% of claims
      associated with MAC involved death or permanent brain damage, similar to general
      anesthesia claims. In contrast, the proportion of regional anesthesia claims with
      death or permanent brain damage was less (P < 0.01). Respiratory depression,
      after absolute or relative overdose of sedative or opioid drugs, was the most
      common (21%, n = 25) specific damaging mechanism in MAC claims. Nearly half of
      these claims were judged as preventable by better monitoring, including
      capnography, improved vigilance, or audible alarms. On-the-patient operating room
      fires, from the use of electrocautery, in the presence of supplemental oxygen
      during facial surgery, resulted in burn injuries in 20 MAC claims (17%).
      CONCLUSION: Oversedation leading to respiratory depression was an important
      mechanism of patient injuries during MAC. Appropriate use of monitoring,
      vigilance, and early resuscitation could have prevented many of these injuries.
      Awareness and avoidance of the fire triad (oxidizer, fuel, and ignition source)
      is essential to prevent on-the-patient fires.

PMID- 16436840
TI  - Ventilator-associated pneumonia leading to acute lung injury after trauma:
      importance of Haemophilus influenzae.
AB  - BACKGROUND: Ventilator-associated pneumonia is a clear risk factor for acute lung
      injury which has been poorly described in trauma patients. This prospective study
      was undertaken to estimate the incidence of such ventilator-associated pneumonia
      leading to acute lung injury, the risk factors, and the associated morbidity and
      mortality in a group of multiple trauma patients. METHODS: Trauma patients who
      were mechanically ventilated and survived at least 24 h were included. Ventilator
      associated pneumonia was confirmed by a bacterial culture of a blind protected
      telescoping catheter with at least 10 colony-forming units/ml of at least one
      pathogen. Episodes of acute lung injury were prospectively recorded. RESULTS:
      Ventilator-associated pneumonia was documented in 78 patients of the 175 included
      (44%) and led to the development of ventilator-associated pneumonia acute lung
      injury in 18 patients (23%). The sole independent risk factor for ventilator
      associated pneumonia leading to acute lung injury was the presence of Haemophilus
      influenzae (hazard ratio, 8.8; 95% confidence interval, 2.7-28.6). Eleven (61%)
      of the 18 patients with ventilator-associated pneumonia leading to acute lung
      injury had development of a ventilator-associated pneumonia recurrence, as
      compared with 20 (33%) of the 60 patients with ventilator-associated pneumonia
      alone (P = 0.03). Seven (39%) of the 18 trauma patients with ventilator
      associated pneumonia leading to acute lung injury died, as compared with 9 (15%)
      of the 60 trauma patients with ventilator-associated pneumonia alone (P = 0.04).
      CONCLUSION: Acute lung injury complicated the course of 15% of ventilator
      associated pneumonia in trauma patients. H. influenzae seemed to be one of the
      most frequent bacteria involved and the sole risk factor identified. Occurrence
      of ventilator-associated pneumonia leading to acute lung injury modified the
      prognosis of trauma patients.

PMID- 16436841
TI  - Intrapatient reproducibility of the BISxp monitor.
AB  - BACKGROUND: The Bispectral Index (BIS) reportedly reflects anesthetic depth. It
      is recommended that anesthetic agents should be titrated to maintain the BIS
      between 40 and 60 arbitrary BIS units during anesthesia. For anesthesia providers
      to follow this recommendation, the monitor should be predictably affected by
      different anesthetic agents and have good interpatient and intrapatient
      reproducibility. The authors hypothesized that when two BISxp devices (Aspect
      Medical Systems, Newton, MA) are placed concurrently on the same patient, their
      readings are concordant throughout the anesthetic period. METHODS: Simultaneous
      BIS recordings from two BISxp monitors were obtained during anesthesia at 5-s
      intervals from 12 participants. RESULTS: In total 22,860 concurrent paired BIS
      readings were obtained. For 10.7% of the time, there were sustained periods of 30
      s or greater where the readings suggested a different depth of anesthesia. For 6%
      of the time, there were sustained periods of 30 s or greater where the readings
      differed by 10 or more arbitrary BIS units. The regression coefficient (R) for
      the two devices was 0.65 (range, 0.35-0.92). There was zero bias between the
      devices, and the 95% limits of agreement ranged between -18 and +17. CONCLUSION:
      A conflicting anesthetic management was suggested by the simultaneous BIS
      readings 10.7% of the time. These results suggest that BISxp does not always
      provide a reproducible single number. Anesthesia providers should not rely
      exclusively on the BIS reading when assessing depth of anesthesia.

PMID- 16436842
TI  - Lightwand tracheal intubation with and without muscle relaxation.
AB  - BACKGROUND: Lightwand tracheal intubation is a suitable technique for patients
      who are difficult to intubate but who are receiving effective ventilation. The
      effect of muscle relaxants on the efficacy of lightwand intubation has not yet
      been evaluated. The authors conducted a prospective, double-blind, placebo
      controlled study to assess the effectiveness and incidence of complications of
      lightwand tracheal intubation performed during general anesthesia with and
      without the use of a muscle relaxant in patients with apparently normal airway
      anatomy. METHODS: One hundred seventy-six patients who required orotracheal
      intubation were prospectively included. Anesthesia was administered using
      propofol (2 mg/kg, then 3 mg . kg (-1). h(-1)) and remifentanil (1 microg/kg,
      then 0.3 microg . kg(-1) . min(-1)). Patients were randomly assigned to one of
      two groups (n = 88 for each) to receive rocuronium 0.6 mg/kg or saline
      intravenously. Lightwand orotracheal intubation (Trachlight; Laerdal Medical
      Inc., Armonk, NY) was attempted after 3 min. The authors recorded the number of
      successful intubations, the number of attempts and their duration, and events
      during the procedure. RESULTS: The failure rate of lightwand intubation was 12%
      in the placebo group and 2% in the rocuronium group (P = 0.021). Patients in the
      placebo group received more multiple intubation attempts (P < 0.001), required a
      greater intubation time (77 +/- 65 vs. 52 +/- 31 s; P = 0.002) and experienced a
      greater incidence of events during intubation (61 vs. 0%; P < 0.001) than
      patients in the rocuronium group. CONCLUSIONS: The use of muscle relaxants in
      patients with apparently normal airways is associated with a lower failure rate,
      decreased intubation time, and fewer attempts when performing lightwand
      orotracheal intubation.

PMID- 16436843
TI  - QT interval measurement: evaluation of automatic QTc measurement and new simple
      method to calculate and interpret corrected QT interval.
AB  - BACKGROUND: Assessment of repolarization duration is often recommended to avoid
      administration of QT-prolonging drugs in patients with prolonged QTc interval, a
      frequent situation in the postoperative period. Bazett QT correction
      inappropriately increases QTc when heart rate is increased, and the use of the
      Fridericia formula may avoid a falsely prolonged QTc interval. The authors
      assessed automatic QT interval measurement to detect prolonged QTc interval
      (women >450 ms; men >440 ms) in the postoperative setting. METHODS: Automatic and
      manual electrocardiograms were performed in 108 patients after anesthesia.
      Automatic electrocardiographic measurement used the Bazett formula. Manual
      measurements were made from each electrocardiogram and used as the reference.
      Agreement between the two methods was analyzed. Bazett and Fridericia QT
      corrections were compared in this population. RESULTS: Agreement between
      automatic and manual measurements was low. The Fridericia correction, but not the
      Bazett correction, was independent from heart rate and allowed adequate QT
      correction. Sensitivity of automatic measurements to detect prolonged QTc-Bazett
      interval was 54%. Automatic QTc-Bazett interval less than 430 ms ruled out a
      manual prolonged QTc interval. When automatic QTc-Bazett was greater than 430 ms,
      this value was converted according to Fridericia. Automatic QTc-Fridericia
      greater than 430 ms identified all patients with prolonged manual QTc with a
      negative predictive error of 0% (95% confidence interval, 0-7%). QTc-Fridericia
      can be approximated by respectively adding or subtracting 5% to the uncorrected
      QT for each increase or decrease by 10 beats/min in heart rate from 60 beats/min.
      CONCLUSIONS: Automatic QTc-Bazett measurement, if abnormal, associated with
      calculation of QTc-Fridericia reliably identifies patients in whom manual QTc
      measurement must be performed to confirm postoperative prolonged QTc interval.

PMID- 16436844
TI  - Devices for lung isolation used by anesthesiologists with limited thoracic
      experience: comparison of double-lumen endotracheal tube, Univent torque control
      blocker, and Arndt wire-guided endobronchial blocker.
AB  - BACKGROUND: Lung isolation is accomplished with a double-lumen tube or a
      bronchial blocker. Previous studies comparing lung isolation methods were
      performed by experienced anesthesiologists in thoracic anesthesia. Therefore, the
      results of these studies may not be relevant to the anesthesiologist with limited
      experience. This study compared the success rates of lung isolation devices among
      anesthesiologists with limited experience in thoracic anesthesia. METHODS: A
      prospective, randomized trial was designed to determine the success and time
      required for proper placement of the left-sided double-lumen tube (n = 22), the
      Univent tube (Vitaid Ltd., Lewiston, NY; n = 22), and the Arndt Blocker (Cook
      Critical Care, Bloomington, IN; n = 22). Anesthesiologists with less than two
      lung isolation cases per month were included (faculty n = 17 and senior residents
      n = 11). Variables recorded included (1) successful placement (as determined by
      an independent observer), (2) time of placement, and (3) the number of times the
      fiberoptic bronchoscope was used. RESULTS: Participants failed to place or
      position their assigned device in 25 of 66 patients (failure was 39% among
      faculty and 36% among senior residents). The failure rate did not differ among
      the three devices (P = 0.65). The median (25th-75th percentile) times to complete
      the placement procedures were as follows: (1) double-lumen tube: 6.1 min (4.6-9.5
      min), (2) Univent tube: 6.7 min (4.9-8.8 min), and (3) Arndt Blocker: 8.6 min
      (5.8-17.5 min) (P = 0.45 comparing all devices). After device malposition was
      identified, it took 1 min or less for the investigating anesthesiologist to
      achieve optimal position. CONCLUSIONS: Anesthesiologists with limited experience
      in thoracic anesthesia frequently fail to successfully place lung isolation
      devices. Rapid successful device placement by an experienced anesthesiologist
      excluded any contribution of uniquely difficult anatomy. The nature of the
      malpositions suggests that the most critical factor in successful placement was
      the anesthesiologist's knowledge of endoscopic bronchial anatomy.

PMID- 16436845
TI  - Impact of postoperative unwashed shed blood retrieved after total knee
      arthroplasty on endotoxin-stimulated tumor necrosis factor alpha release in
      vitro.
AB  - BACKGROUND: : Allogeneic or autologous blood seems to have an immunosuppressive
      effect that is largely attributable to storage-dependent factors. However,
      transfusion of postoperative unwashed shed blood (USB) after elective total knee
      replacement does not undergo storage. Therefore, the authors explored the effects
      of USB on the mitogen-driven cytokine synthesis by the patient's peripheral blood
      mononuclear cells. METHODS: : Perioperative blood samples were obtained from 12
      total knee replacement patients with and 5 without reinfusion of leukoreduced
      USB, and from USB reinfusion line, before and after leukoreduction. Venous blood
      obtained at 4-6 postoperative hours was coincubated with USB. Endotoxin
      stimulated release of tumor necrosis factor alpha and interleukin 10 was measured
      after 24 h of culture by solid-phase enzyme-labeled chemiluminescent immunometric
      assay. RESULTS: : Coincubation of postoperative venous blood with USB, USB cells,
      or USB plasma resulted in a significant depression of tumor necrosis factor-alpha
      synthesis, without significant effects on interleukin-10 synthesis. However, no
      differences were observed for endotoxin-stimulated cytokine release in
      perioperative blood samples from patients receiving or not receiving USB.
      CONCLUSION: : These data suggest that USB seemed to contain an antiinflammatory
      agent. However, at the actual retransfusion rate, USB does not seem to further
      enhance the immunosuppression that follows knee replacement surgery.

PMID- 16436846
TI  - Effects of general anesthesia on anandamide blood levels in humans.
AB  - BACKGROUND: The endocannabinoid system includes G-protein-coupled cannabinoid
      receptors, the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2
      arachidonoylglycerol, and multiple enzymes involved in the biosynthesis and
      degradation of endocannabinoids, including the anandamide metabolizing enzyme
      fatty acid amide hydrolase. Endocannabinoids play an important role in the
      physiologic control of sleep, pain processing, and emesis. The authors therefore
      investigated the effects of general anesthesia on the endocannabinoid system in
      humans. METHODS: The authors measured whole blood levels of anandamide in 12
      patients after induction of general anesthesia with etomidate (an agent shown to
      have no effect on anandamide levels) and maintenance of anesthesia with the
      volatile agent sevoflurane as well as in 12 patients undergoing total intravenous
      anesthesia with propofol, a known inhibitor of fatty acid amide hydrolase in the
      mouse brain. Anandamide levels were measured using high-performance liquid
      chromatography-tandem mass spectrometry at four time points (before and at 10,
      20, 30, and 40 min after induction of anesthesia). RESULTS: Patients of the
      sevoflurane group showed a significant decline in anandamide levels from
      induction of anesthesia to 40 min after induction, whereas anandamide levels in
      patients of the propofol group remained unchanged (type III sum of squares =
      1725.66, F = 162.60, P < 0.001, repeated-measures analysis of variance).
      CONCLUSION: General anesthesia influences the endocannabinoid system in a drug
      dependent way, which may explain side effects of general anesthetics such as
      psychomimetic and antiemetic properties of propofol and the high incidence of
      postoperative nausea and vomiting after volatile anesthetics. These findings
      suggest new targets for anesthetic drug development.

PMID- 16436847
TI  - Comparative effects of vaporized perfluorohexane and partial liquid ventilation
      in oleic acid-induced lung injury.
AB  - BACKGROUND: It is currently not known whether vaporized perfluorohexane is
      superior to partial liquid ventilation (PLV) for therapy of acute lung injury. In
      this study, the authors compared the effects of both therapies in oleic acid
      induced lung injury. METHODS: Lung injury was induced in 30 anesthetized and
      mechanically ventilated pigs by means of central venous infusion of oleic acid.
      Animals were assigned to one of the following groups: (1) control or gas
      ventilation (GV), (2) 2.5% perfluorohexane vapor, (3) 5% perfluorohexane vapor,
      (4) 10% perfluorohexane vapor, or (5) PLV with perfluorooctane (30 ml/kg). Two
      hours after randomization, lungs were recruited and positive end-expiratory
      pressure was adjusted to obtain minimal elastance. Ventilation was continued
      during 4 additional hours, when animals were killed for lung histologic
      examination. RESULTS: Gas exchange and elastance were comparable among vaporized
      perfluorohexane, PLV, and GV before the open lung approach was used and improved
      in a similar fashion in all groups after positive end-expiratory pressure was
      adjusted to optimal elastance (P < 0.05). A similar behavior was observed in
      functional residual capacity (FRC) in animals treated with vaporized
      perfluorohexane and GV. Lung resistance improved after recruitment (P < 0.05),
      but values were higher in the 10% perfluorohexane and PLV groups as compared with
      GV (P < 0.05). Interestingly, positive end-expiratory pressure values required to
      obtain minimal elastance were lower with 5% perfluorohexane than with PLV and GV
      (P < 0.05). In addition, diffuse alveolar damage was significantly lower in the
      5% and 10% perfluorohexane vapor groups as compared with PLV and GV (P < 0.05).
      CONCLUSIONS: Although the use of 5% vaporized perfluorohexane permitted the
      authors to reduce pressures needed to stabilize the lungs and was associated with
      better histologic findings than were PLV and GV, none of these perfluorocarbon
      therapies improved gas exchange or lung mechanics as compared with GV.

PMID- 16436848
TI  - Cerebral blood flow affects dose requirements of intracarotid propofol for
      electrocerebral silence.
AB  - BACKGROUND: The authors hypothesized that cerebral blood flow (CBF) changes will
      affect the dose of intracarotid propofol required to produce electrocerebral
      silence. METHODS: The authors tested their hypothesis on New Zealand White
      rabbits. The first group of 9 animals received intracarotid propofol during (1)
      normoventilation, (2) hyperventilation, and (3) hypoventilation. The second group
      of 14 animals received intracarotid propofol with or without concurrent
      intraarterial verapamil, a potent cerebral vasodilator. The third group of 8
      animals received bolus injection of propofol during normotension, during severe
      cerebral hypoperfusion, and after hemodynamic recovery. RESULTS: In the first
      group, there was a linear correlation between the dose of intracarotid propofol
      and percent change (%Delta) in CBF from the baseline due to changes in the minute
      ventilation, Total Dose (y) = 0.17 + 0.012 * %Delta CBF (x), n = 27, r = 0.76. In
      the second group, the dose of propofol was also a function of CBF change after
      verapamil, Total Dose (y) = 0.98 + 0.1 * %Delta CBF (x), n = 14, r = 0.75. In the
      third group, the duration of electrocerebral silence after intracarotid propofol
      (3 mg) was significantly increased with concurrent cerebral hypoperfusion
      compared with prehypoperfusion and posthypoperfusion values (141 +/- 38 vs. 19 +/
      24 and 16 +/- 12 s, respectively, P < 0.0001). CONCLUSIONS: The authors conclude
      that CBF affects the dose requirements of intracarotid propofol required to
      produce electrocerebral silence. Furthermore, the manipulation of CBF might be a
      useful tool to enhance the efficacy of intracarotid drugs.

PMID- 16436849
TI  - Expansion of gas bubbles by nitrous oxide and xenon.
AB  - BACKGROUND: Nitrous oxide is well known to expand gas bubbles trapped in enclosed
      spaces and is contraindicated in situations where this may occur. Xenon, an
      anesthetic gas with similar physical properties to nitrous oxide, is also likely
      to expand gas bubbles, and it has been predicted that microbubbles in the
      circulation may expand dramatically when exposed to xenon. Because of the
      possibility that xenon will be used during cardiopulmonary bypass surgery, a
      procedure that is likely to introduce microbubbles into the circulation, the
      authors reinvestigated the extent to which xenon expands gas bubbles in aqueous
      solution. METHODS: Gas bubbles of either air or oxygen were formed in an aqueous
      solution, and their size was monitored using optical microscopy when they were
      exposed to a rapidly flowing solution of xenon, nitrous oxide, or a xenon-oxygen
      mixture. RESULTS: Both nitrous oxide and xenon rapidly expanded air bubbles,
      although nitrous oxide caused a much larger expansion. The observed expansion was
      not greatly dependent on the initial size of the bubble but was significantly
      greater at lower temperatures. Under conditions relevant to cardiopulmonary
      bypass surgery (50% xenon-50% oxygen, 30 degrees C), the increase in diameter was
      modest (9.7 +/- 0.8%). CONCLUSIONS: Although xenon does expand small air and
      oxygen bubbles, the extent to which this occurs under clinically relevant
      conditions of concentration and temperature is modest.

PMID- 16436850
TI  - Sonographic visualization and ultrasound-guided block of the third occipital
      nerve: prospective for a new method to diagnose C2-C3 zygapophysial joint pain.
AB  - BACKGROUND: Chronic neck pain after whiplash injury is caused by cervical
      zygapophysial joints in 50% of patients. Diagnostic blocks of nerves supplying
      the joints are performed using fluoroscopy. The authors' hypothesis was that the
      third occipital nerve can be visualized and blocked with use of an ultrasound
      guided technique. METHODS: In 14 volunteers, the authors placed a needle
      ultrasound-guided to the third occipital nerve on both sides of the neck. They
      punctured caudal and perpendicular to the 14-MHz transducer. In 11 volunteers,
      0.9 ml of either local anesthetic or normal saline was applied in a randomized,
      double-blind, crossover manner. Anesthesia was controlled in the corresponding
      skin area by pinprick and cold testing. The position of the needle was controlled
      by fluoroscopy. RESULTS: The third occipital nerve could be visualized in all
      subjects and showed a median diameter of 2.0 mm. Anesthesia was missing after
      local anesthetic in only one case. There was neither anesthesia nor
      hyposensitivity after any of the saline injections. The C2-C3 joint, in a
      transversal plane visualized as a convex density, was identified correctly by
      ultrasound in 27 of 28 cases, and 23 needles were placed correctly into the
      target zone. CONCLUSIONS: The third occipital nerve can be visualized and blocked
      with use of an ultrasound-guided technique. The needles were positioned
      accurately in 82% of cases as confirmed by fluoroscopy; the nerve was blocked in
      90% of cases. Because ultrasound is the only available technique today to
      visualize this nerve, it seems to be a promising new method for block guidance
      instead of fluoroscopy.

PMID- 16436851
TI  - Ultrasound examination and localization of the sciatic nerve: a volunteer study.
AB  - BACKGROUND: Few studies have examined the use of ultrasound for sciatic nerve
      localization. The authors evaluated the usefulness of low-frequency ultrasound in
      identifying the sciatic nerve at three locations in the lower extremity and in
      guiding needle advancement to target before nerve stimulation. METHODS: In this
      prospective observational study, 15 volunteers underwent sciatic nerve
      examination using a curved ultrasound probe in the range of 2-5 MHz and a Philips
      ATL 5000 unit (ATL Ultrasound, Bothell, WA) in the gluteal, infragluteal, and
      proximal thigh regions. Thereafter, an insulated block needle was advanced inline
      with the ultrasound beam to reach the nerve target, which was further confirmed
      by electrical stimulation. The quality of sciatic nerve images, ease of needle to
      nerve contact, threshold stimulating current, and resultant motor response were
      recorded. RESULTS: The sciatic nerve was successfully identified in the
      transverse view as a solitary predominantly hyperechoic structure on ultrasound
      in all of the three regions examined. The target nerve was visualized easily in
      87% and localized within two needle attempts in all patients. Nerve stimulation
      was successful in 100% after two attempts with a threshold current of 0.42 +/-
      0.12 (mean +/- SD) eliciting foot plantarflexion or dorsiflexion. CONCLUSIONS:
      These preliminary data show that a curved 2- to 5-MHz ultrasound probe provides
      good quality sciatic nerve imaging in the gluteal, infragluteal, and proximal
      thigh locations. Ultrasound-assisted sciatic nerve localization is potentially
      valuable for clinical sciatic nerve blocks.

PMID- 16436852
TI  - Reduction of verbal pain scores after anterior cruciate ligament reconstruction
      with 2-day continuous femoral nerve block: a randomized clinical trial.
AB  - BACKGROUND: Single-injection femoral nerve block analgesia and spinal anesthesia
      have been associated with fewer postoperative nursing interventions and
      successful same-day discharge after anterior cruciate ligament reconstruction. In
      the current study, the authors prospectively determined the effect of continuous
      femoral nerve block on a numeric rating scale (NRS) of pain intensity with
      movement for 7 postoperative days. METHODS: Patients undergoing this surgery with
      no history of previous invasive surgery on the same knee were recruited for this
      study. After standardized spinal anesthesia, intravenous sedation, and
      perioperative multimodal analgesia, patients received a femoral nerve catheter
      with (1) saline bolus (30 ml) plus saline infusion (270 ml at 5 ml/h, placebo
      group); (2) levobupivacaine (0.25%) bolus with saline infusion (group I), or (3)
      levobupivacaine (0.25%) bolus and infusion (group II). Patients were surveyed
      preoperatively and on postoperative days 1-4 and 7 to determine NRS scores (scale
      0-10). RESULTS: Data from 233 participants were analyzed. On days 1-2, 50% of
      placebo patients had NRS scores of 5 or above, whereas among group II patients,
      only 25% had scores of 5 or above (P < 0.001). In regression models for NRS
      scores during days 1-4, group II was the only factor predicting lower pain scores
      (odds ratios, 0.3-0.5; P = 0.001-0.03). Overall, patients with preoperative NRS
      scores greater than 2 were likely to report higher NRS scores during days 1-7
      (odds ratios, 3.3-5.2; P < 0.001). CONCLUSIONS: Femoral nerve block catheters
      reliably keep NRS scores below the moderate-to-severe pain threshold for the
      first 4 days after anterior cruciate ligament reconstruction.

PMID- 16436853
TI  - Increased expression of cyclooxygenase and nitric oxide isoforms, and exaggerated
      sensitivity to prostaglandin E2, in the rat lumbar spinal cord 3 days after L5-L6
      spinal nerve ligation.
AB  - BACKGROUND: Spinal prostaglandins seem to be important in the early pathogenesis
      of experimental neuropathic pain. Here, the authors investigated changes in the
      expression of cyclooxygenase and nitric oxide synthase (NOS) isoforms in the
      lumbar, thoracic, and cervical spinal cord and the pharmacologic sensitivity to
      spinal prostaglandin E2 (PGE2) after L5-L6 spinal nerve ligation (SNL). METHODS:
      Male Sprague-Dawley rats, fitted with intrathecal catheters, underwent SNL or
      sham surgery 3 days before experimentation. Paw withdrawal threshold was
      monitored for up to 20 days. Immunoblotting, spinal glutamate release, and
      behavioral testing were examined 3 days after SNL. RESULTS: Allodynia (paw
      withdrawal threshold < or = 4 g) was evident 1 day after SNL and remained stable
      for 20 days. Paw withdrawal threshold was unchanged (P > 0.05) from baseline (>
      15 g) after sham surgery except for a small but significant decrease on day 20.
      Cyclooxygenase 2, neuronal NOS, and inducible NOS were significantly increased in
      the ipsilateral lumbar dorsal horn after SNL. Expression in the contralateral
      dorsal horn and ventral horns (lumbar segments) or bilaterally (thoracic and
      cervical segments) was unchanged from sham controls. This was accompanied by a
      significant decrease in both the EC50 of PGE2-evoked glutamate release and the
      ED50 of PGE2 on brush-evoked allodynia. Enhanced sensitivity to PGE2 was
      localized to lumbar segments of SNL animals and attenuated by SC-51322 or S(+)
      ibuprofen, but not R(-)-ibuprofen (100 mum). CONCLUSION: The increased expression
      of cyclooxygense-2, neuronal NOS, and inducible NOS and the enhanced sensitivity
      to PGE2 in spinal segments affected by SNL support the hypothesis that spinal
      prostanoids play an early pathogenic role in experimental neuropathic pain.

PMID- 16436854
TI  - Actions of midazolam on excitatory transmission in dorsal horn neurons of adult
      rat spinal cord.
AB  - BACKGROUND: Although intrathecal administration of midazolam, a water-soluble
      imidazobenzodiazepine derivative, has been found to produce analgesia, how it
      exerts this effect at the neuronal level in the spinal cord is not fully
      understood. METHODS: The effects of midazolam on electrically evoked and
      spontaneous excitatory transmission were examined in lamina II neurons of adult
      rat spinal cord slices using the whole cell patch clamp technique. RESULTS: Bath
      applied midazolam (1 microm) diminished Adelta- and C-fiber evoked polysynaptic
      excitatory postsynaptic currents in both amplitude and integrated area. However,
      it affected neither Adelta- and C-fiber evoked monosynaptic excitatory
      postsynaptic currents in amplitude nor miniature excitatory postsynaptic currents
      in amplitude, frequency, and decay time constant. In the presence of a
      benzodiazepine receptor antagonist, flumazenil (5 microm), midazolam (1 microm)
      did not diminish Adelta-fiber evoked polysynaptic excitatory postsynaptic
      currents, suggesting that midazolam modulate the gamma-aminobutyric acid
      interneurons in the dorsal horn. CONCLUSIONS: Midazolam reduced excitatory
      synaptic transmission by acting on the gamma-aminobutyric acid type
      A/benzodiazepine receptor in interneurons, leading to a decrease in the
      excitability of spinal dorsal horn neurons. This may be a possible mechanism for
      the antinociception by midazolam in the spinal cord.

PMID- 16436855
TI  - Age-dependent responses to nerve injury-induced mechanical allodynia.
AB  - BACKGROUND: Developmental differences in responses to acute and chronic nerve
      injury have received minimal attention. This study examines developmental
      differences in behavioral responses to a proximal (closer to the spinal cord) (L5
      and L6 spinal nerve root ligation) or to a more distal (closer to peripheral
      innervation) (partial sciatic nerve ligation) nerve injury in rats paralleling
      the infant to young adult human. METHODS: Withdrawal thresholds to von Frey
      filament testing in the hind paw were determined before and various times after
      either spinal nerve root ligation or partial sciatic nerve ligation in rats aged
      2, 4, and 16 weeks. Control rats of these ages were observed serially without
      surgery. Times for withdrawal thresholds to mechanical stimuli to return to 80%
      of that of the hind paw in the control animals were compared among the different
      ages in the two models. RESULTS: Baseline withdrawal thresholds in younger rats
      were lower (P < 0.05). In the 2-week-old animals, distal injury partial sciatic
      nerve ligation did not cause a reduction in withdrawal threshold from baseline.
      This was different from the spinal nerve root ligation group and the older
      animals in the partial sciatic nerve ligation group. However, when compared with
      age-matched control animals, both nerve injuries resulted in reduced withdrawal
      thresholds (P < 0.05). The resolution of hypersensitivity to mechanical
      stimulation, as measured by return of threshold to 80% of controls, occurred more
      quickly in 2-week-old than in 4- and 16-week-old animals in both injury models (P
      < 0.05). CONCLUSION: These data suggest that resolution of sensitization to A
      fiber input occurs more rapidly in young animals. In addition, distal injury has
      less of a sensitizing effect on A-fiber input than proximal injury in the younger
      animals. The authors speculate that neuroimmune responses, especially at the site
      of injury, are developmentally regulated and less likely to produce chronic pain
      when injury occurs at a young age.

PMID- 16436856
TI  - Perineural clonidine reduces mechanical hypersensitivity and cytokine production
      in established nerve injury.
AB  - BACKGROUND: Partial sciatic nerve ligation (PSNL) produces axonal damage, a local
      inflammatory response, and wallerian degeneration. Cytokines secreted near the
      site of nerve injury are thought to play important roles in development and
      maintenance of central sensitization and neuropathic pain. Injection of clonidine
      at the site and time of nerve injury slows the development of PSNL-induced
      hypersensitivity and reduces local cytokine expression by actions on alpha2
      adrenoceptors. The current study tested whether clonidine would have a similar
      effect in established nerve injury. METHODS: Rats underwent unilateral PSNL, and
      perineural saline, clonidine, or BRL44408 plus clonidine was injected 2 weeks
      later. Three days after perineural injection, withdrawal threshold to mechanical
      stimulation of the hind paw ipsilateral and contralateral to PSNL was determined,
      and tissues were removed for cytokine analysis. RESULTS: PSNL was accompanied by
      a proinflammatory pattern of cytokine content in neural structures and
      hypersensitivity ipsilaterally with few changes contralaterally. Perineural
      clonidine, but not saline, partially reversed the hypersensitivity, accompanied
      by reduced concentrations of interleukin 6 and interleukin 1beta in the sciatic
      nerve. The effect of clonidine on hypersensitivity and these cytokines was
      blocked by the alpha2-adrenoceptor antagonist, BRL44408. CONCLUSIONS: These data
      suggest that perineural clonidine acts on alpha2 adrenoceptors to reduce
      hypersensitivity in established nerve injury, likely by an immunomodulatory
      mechanism, and may be effective in patients in the weeks after nerve injury.

PMID- 16436857
TI  - Perioperative abstinence from cigarettes: physiologic and clinical consequences.
AB  - Chronic exposure to cigarette smoke produces profound changes in physiology that
      may alter responses to perioperative interventions and contribute to
      perioperative morbidity. Because of smoke-free policies in healthcare facilities,
      all smokers undergoing surgery are abstinent from cigarettes for at least some
      period of time so that all are in various stages of recovery from the effects of
      smoke. Understanding this recovery process will help perioperative physicians
      better treat these patients. This review examines current knowledge regarding how
      both short-term (duration ranging from hours to weeks) and long-term smoking
      cessation affects selected physiology and pathophysiology of particular relevance
      to perioperative outcomes and how these changes affect perioperative risk. It
      will also consider current evidence regarding how nicotine replacement therapy, a
      valuable adjunct to help patients maintain abstinence, may affect perioperative
      physiology.

PMID- 16436858
TI  - Ultrasound-guided regional anesthesia: current state of the art.

PMID- 16436859
TI  - Postsurgical safety of opioid-sparing cyclooxygenase-2 inhibitors.

PMID- 16436860
TI  - Facilitating endotracheal tube advancement during fiberscope-assisted intubation:
      giving due credit.

PMID- 16436862
TI  - Difficulties in advancing an endotracheal tube over a fiberoptic bronchoscope.

PMID- 16436863
TI  - Fiberoptic intubation.

PMID- 16436864
TI  - Corniculate cartilages are wrongly labeled arytenoid cartilages.

PMID- 16436865
TI  - Markedly displaced arytenoid cartilage during fiberoptic orotracheal intubation.

PMID- 16436866
TI  - UNDO your troubles with the tube: how to improve your success with endotracheal
      tube passage during fiberoptic intubation.

PMID- 16436868
TI  - Preoxygenation during pregnancy in the head-up versus the supine position.

PMID- 16436870
TI  - Mechanism of benefit of head-up preoxygenation in obese patients.

PMID- 16436871
TI  - Sildenafil for pulmonary hypertension in pregnancy?

PMID- 16436872
TI  - Effectiveness of isoflurane in inducing delayed preconditioning against
      myocardial infarction in vivo.

PMID- 16436876
TI  - Implications of postoperative pruritus.

PMID- 16436877
TI  - Drug-induced prolongation of the QT interval: what's the point?

PMID- 16436879
TI  - Droperidol has been reported to cause serious arrhythmias.

PMID- 16436880
TI  - Preoxygenation in claustrophobic patients.

PMID- 16436882
TI  - Outcomes of the First International Conference on Pediatric Mechanical
      Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion.

PMID- 16436883
TI  - Modeling ventricular function during cardiac assist: does time-varying elastance
      work?
AB  - The time-varying elastance theory of Suga et al. is widely used to simulate left
      ventricular function in mathematical models and in contemporary in vitro models.
      We investigated the validity of this theory in the presence of a left ventricular
      assist device. Left ventricular pressure and volume data are presented that
      demonstrate the heart-device interaction for a positive-displacement pump
      (Novacor) and a rotary blood pump (Medos). The Novacor was implanted in a calf
      and used in fixed-rate mode (85 BPM), whereas the Medos was used at several flow
      levels (0-3 l/min) in seven healthy sheep. The Novacor data display high beat-to
      beat variations in the amplitude of the elastance curve, and the normalized
      curves deviate strongly from the typical bovine curve. The Medos data show how
      the maximum elastance depends on the pump flow level. We conclude that the
      original time-varying elastance theory insufficiently models the complex
      hemodynamic behavior of a left ventricle that is mechanically assisted, and that
      there is need for an updated ventricular model to simulate the heart-device
      interaction.

PMID- 16436884
TI  - Artificial heart research and present status of clinical application in Japan.
AB  - Japan has a long history of research and development of the artificial heart
      since Atsumi began studying artificial hearts at the University of Tokyo in 1959.
      Since that time, the University of Tokyo group has been developing different
      types of artificial hearts, as well as materials, blood pumps, driving
      mechanisms, and control methods. Other than the University of Tokyo, there are 12
      institutes involved in artificial heart research and development in Japan. As for
      artificial heart clinical application in Japan, four devices were approved by the
      government; two are domestic, two are imported. Between 1980 and 2004, 697 cases
      of clinical application of a ventricular assist device (VAD) have been performed,
      including in 38 pediatric patients under 18 years. Recently, clinical use of
      percutaneous cardiopulmonary support has been increasing with 600 to 800 cases
      being performed every year, including in 40 to 60 patients under age 20 years.
      Although the requirement for clinical use of pediatric VADs is increasing, there
      is no device, domestic or imported, currently used in Japan; therefore, there is
      an urgent need for development of a pediatric VAD.

PMID- 16436885
TI  - Microtextured materials for circulatory support devices: preliminary studies.
AB  - Thromboembolic events (TE) associated with circulatory support devices are a
      major source of mortality and morbidity. Clinically, the lowest TE rates are
      claimed with devices that incorporate textured blood-contacting materials. The
      textured materials currently used in circulatory assist devices are composed of
      small, attached fibers that form the boundaries of connected cavities. These
      cavities entrap blood components to form a "neointimal" layer, which is believed
      to minimize thromboembolic events. We believe that the three-dimensional surface
      topography of blood-contacting materials is a major controlling factor in the
      formation of a stable neointimal layer upon the material. Particle-cast cavities
      were used to form geometric features in segmented polyurethane. This
      microtextured material was incorporated as part of a flexible blood-contacting
      surface in a blood pump that was implanted as a left ventricular assist device in
      calves. The structure, thickness, stability, and development of the neointimal
      layer were then evaluated. These preliminary studies have shown that a stable
      neointimal layer can be formed upon the particle-cast surfaces. The results also
      indicate that the cavity size on the particle-cast surfaces has a significant
      effect on neointimal adhesion. The methods employed can be used in the design of
      future circulatory support devices.

PMID- 16436886
TI  - Neurocognitive function in patients with ventricular assist devices: a comparison
      of pulsatile and continuous blood flow devices.
AB  - The effect of successful ventricular assist device (VAD) implantation on
      neurocognitive function in terminal heart failure is uncertain. Additionally, the
      different impact of continuous versus pulsatile blood flow devices is unknown. A
      total of 29 patients (mean age 53 years), surviving implantation of a ventricular
      assist device as bridge to transplantation were prospectively followed
      (continuous flow: Micromed DeBakey, n = 11; pulsatile flow: Thoratec and Novacor,
      n = 18). Normative data were obtained in 40 age- and sex-matched healthy subjects
      (mean age 54 years). Neurocognitive function was objectively measured by means of
      cognitive P300 auditory evoked potentials before operation (baseline), at
      intensive care unit (ICU) discharge, and at the 8-week and 12-week follow-up.
      Before implantation of the VAD, cognitive P300 evoked potentials were impaired
      (prolonged) compared with age- and sex-matched healthy subjects (p < 0.001).
      After successful VAD implantation, P300 evoked potentials markedly improved
      compared with before operation (ICU discharge, p = 0.007; 8-week follow-up, p =
      0.022; 12-week follow-up, p < 0.0001). Importantly, there was no difference
      between continuous and pulsatile VADs (before operation, p = 0.676; ICU
      discharge, p = 0.736; 8-week follow-up, p = 0.911 and 12-week follow-up, p =
      0.397; respectively). Nevertheless, P300 peak latencies did not fully normalize
      at 12-week follow-up compared with healthy subjects (p = 0.012). Successful VAD
      implantation improves neurocognitive impairment in patients with terminal heart
      failure. Importantly, this effect is independent of the type of VAD (pulsatile
      vs. continuous blood flow).

PMID- 16436887
TI  - Thrombogenic performance of a st. Jude bileaflet mechanical heart valve in a
      sheep model.
AB  - The sheep model is preferred for chronic evaluation of prosthetic heart valves,
      surgical techniques, and endocardiographic studies. A bileaflet mechanical heart
      valve (MHV) was implanted into a sheep model to study its in vivo performance and
      to evaluate the thrombogenic potential of the valve. Transesophageal
      echocardiography and transcranial Doppler ultrasonography measurements were
      conducted before and after the valve implantation. Platelet activity state (PAS)
      assay measurements were also conducted before and after the implantation surgery.
      After sheep euthanasia, the MHV was explanted and scanning electron microscopy
      (SEM) was performed on the explanted valve to examine changes to the MHV surface.
      Tissue blocks were taken from the sheep brain, left ventricle, aorta, spleen, and
      lung lobes for histological examination. Our results indicated that after the MHV
      implantation, more embolic signals were detected in the sheep carotid artery,
      increasing monotonously as a function of implantation time. Echocardiographic
      parameters including blood aortic velocity, transvalvular pressure gradient, and
      velocity time integral increased. PAS increased significantly after valve
      implantation. SEM pictures demonstrated calcium and phosphate deposition on the
      valve surfaces. Histological examination demonstrated hemorrhage in the lung
      tissue, pulmonary thrombosis, and osteogenesis in heart tissue.

PMID- 16436888
TI  - An in vitro study of changing profile heights in mitral bioprostheses and their
      influence on flow.
AB  - In vitro assessment of different profiles for prosthetic mitral valves can result
      in better understanding of the physics of transmitral flow for each design. It
      has been postulated that decreasing the profile height of the mitral
      bioprosthetic valve has potential clinical benefit. In the present study, we
      compared the atrial and ventricular flow characteristics in different conditions
      using Carpentier-Edwards Perimount mitral valves with various profile heights.
      Each valve was placed at the intersection of the left ventricle, made of
      transparent silicone rubber, and the left atrium in Caltech's left heart pulsed
      flow simulator system. Digital particle image velocimetry has been used as the
      quantitative flow visualization technique. With the intention of studying the
      blood wash out around each valve, circulation and particle residence time were
      computed based on the vorticity and velocity fields around each valve,
      respectively. Results show that by increasing the profile's height at the atrial
      side of the valve, the magnitude of circulation near the atrial side of the valve
      decreases while particle residence time increases. However, extreme reduction of
      profile height in the ventricular side may increase the magnitude of circulation
      around the valve and decrease the particle residence time.

PMID- 16436889
TI  - Predicted hemodynamic benefits of counterpulsation therapy using a superficial
      surgical approach.
AB  - A volume-displacement counterpulsation device (CPD) intended for chronic
      implantation via a superficial surgical approach is proposed. The CPD is a
      pneumatically driven sac that fills during native heart systole and empties
      during diastole through a single, valveless cannula anastomosed to the subclavian
      artery. Computer simulation was performed to predict and compare the
      physiological responses of the CPD to the intraaortic balloon pump (IABP) in a
      clinically relevant model of early stage heart failure. The effect of device
      stroke volume (0-50 ml) and control modes (timing, duration, morphology) on
      landmark hemodynamic parameters and the LV pressure-volume relationship were
      investigated. Simulation results predicted that the CPD would provide hemodynamic
      benefits comparable to an IABP as evidenced by up to 25% augmentation of peak
      diastolic aortic pressure, which increases diastolic coronary perfusion by up to
      34%. The CPD may also provide up to 34% reduction in LV end-diastolic pressure
      and 12% reduction in peak systolic aortic pressure, lowering LV workload by up to
      26% and increasing cardiac output by up to 10%. This study demonstrated that the
      superficial CPD technique may be used acutely to achieve similar improvements in
      hemodynamic function as the IABP in early stage heart failure patients.

PMID- 16436890
TI  - Slow continuous ultrafiltration with bound solute dialysis.
AB  - Bound solute dialysis (BSD), often referred to as "albumin dialysis" (practiced
      clinically as the molecular adsorbents recirculating system, MARS, or single-pass
      albumin dialysis, SPAD) or "sorbent dialysis" (practiced clinically as the
      charcoal-based Biologic-DT), is based upon the thermodynamic principle that the
      driving force for solute mass transfer across a dialysis membrane is the
      difference in free solute concentration across the membrane. The clinically
      relevant practice of slow continuous ultrafiltration (SCUF) for maintenance of
      patients with liver failure is analyzed in conjunction with BSD. The primary
      dimensionless operating parameters that describe SCUF-BSD include (1) beta, the
      dialysate/blood binder concentration ratio; (2) kappa, the dialyzer mass
      transfer/blood flow rate ratio; (3) alpha, the dialysate/blood flow rate ratio;
      and, (4) gamma, the ultrafiltration/blood flow rate ratio. Results from
      mathematical modeling of solute removal during a single pass through a dialyzer
      and solute removal from a one-compartment model indicate that solute removal is
      remarkably insensitive to gamma. Solute removal approaches an asymptote
      (improvement in theoretical clearance over that obtainable with no binder in the
      dialysate) with increasing beta that is dependent on kappa and independent of
      alpha. The amount of binder required to approach the asymptote decreases with
      increasing solute-binder equilibrium constant, i.e., more strongly bound solutes
      require less binder in the dialysate. The results of experimental observations
      over a range of blood flow rates, 100 to 180 mL/min, dialysate flow rates, 600 to
      2150 mL/h, ultrafiltration rates, 0 to 220 mL/h, and dialysate/blood albumin
      concentration ratios, beta = 0.01 to 0.04, were independently predicted
      remarkably well by the one-compartment model (with no adjustable parameters)
      based on BSD principles.

PMID- 16436891
TI  - Continuous renal replacement therapy for congestive heart failure: the wearable
      continuous ultrafiltration system.
AB  - Ultrafiltration is effective in the treatment of fluid and sodium overload in
      congestive heart failure. There is no available device to provide this therapy to
      ambulatory patients. We built and tested in vivo a wearable belt that can provide
      continuous ultrafiltration, 168 hours a week. Nine pigs underwent ureteral
      ligation and subsequently were allowed fluids ad lib, producing fluid overload.
      Next day, ultrafiltration was performed for 8 hours. The device consists of a
      hollow-fiber filter, a 9 V battery-operated pulsatile blood pump, a micro pump
      for heparin infusion, and another micro pump to control ultrafiltration rate.
      Blood flow was 65 ml/min and the weight of the device is less than 2.5 lb. Fluid
      removal rate ranged from 0 to 700 ml/h and averaged 106 ml/h. Salt removed was
      7.6 g. No complications were observed. The potential impact on the quality of
      life of these patients by reducing the shortness of breath, leg swelling, and
      returning their ability to enjoy salt in their food might be significant, and a
      reduction in morbidity could be expected. The economic impact in reducing
      hospital admissions and length of stay, intensive care unit utilization, and drug
      consumption could be significant. Further studies are needed to compare this
      innovative approach with traditional drug-based therapy.

PMID- 16436892
TI  - Effects of acetate-free double-chamber hemodiafiltration and standard dialysis on
      systemic hemodynamics and troponin T levels.
AB  - Using acetate as a buffer during hemodialysis is recognized to predispose to
      intradialytic hypotension; however, bicarbonate-based dialysis is not acetate
      free. Paired hemodiafiltration (PHF) is a novel online acetate-free technique. We
      investigated whether PHF is capable of abrogating the changes in systemic
      hemodynamics and troponin T (cTnT) seen with conventional hemodialysis. Twelve
      patients entered a randomized crossover study. Blood pressure (BP) and a full
      range of hemodynamic variables were measured throughout PHF and standard dialysis
      using continuous pulse wave analysis. We also measured predialysis cTnT in 54
      stable and unstable dialysis patients. BP was lower during PHF but without
      increased instability. Stoke volume and cardiac output declined progressively
      during both treatments but to a much lesser extent during PHF (p = 0.003, p <
      0.0001 respectively), whereas peripheral resistance rose to a larger degree
      during hemodialysis (p < 0.0001). cTnT levels were lower before PHF as compared
      with hemodialysis (p = 0.023), with levels falling after PHF and rising after
      hemodialysis (p < 0.0001). In the supplementary patient group, predialysis median
      serum cTnT was higher in the unstable patients (p = 0.0001). This study
      demonstrates that PHF (without exposure to acetate) is associated with less
      deterioration in systemic hemodynamics, maintenance of BP, and less suppression
      of myocardial contractility as compared with bicarbonate dialysis.

PMID- 16436893
TI  - In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic
      kidney disease.
AB  - Chronic kidney disease may progress to end-stage renal disease, which requires
      dialysis or kidney transplantation. No generally applicable therapies to slow
      progression of renal disease are available. Bacteriotherapy affords a promising
      approach to mitigate uremic intoxication by ingestion of live microbes able to
      catabolize uremic solutes in the gut. The present study evaluates the
      nonpathogenic soil-borne alkalophilic urease-positive bacterium Sporosarcina
      pasteurii (Sp) as a potential urea-targeted component for such "enteric dialysis"
      formulation. Data presented herein suggest that Sp survives through exposure to
      gastric juice retaining the ability to hydrolyze urea. In vitro, 10 cfu (colony
      forming units) of Sp removed from 21 +/- 4.7 mg to 228 +/- 6.7 mg urea per hour,
      depending on pH, urea concentration, and nutrient availability. Beneficial
      effects of Sp on fermentation parameters in the intestine were demonstrated in
      vitro in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)
      inoculated with fecal microbiota. Enumeration of marker organisms suggested that
      presence of Sp does not disturb microbial community of the SHIME. Additionally, a
      pilot study in 5/6th nephrectomized rats fed 10 cfu of live Sp daily throughout
      the study demonstrated that the tested regimen reduced blood urea-nitrogen levels
      and significantly prolonged the lifespan of uremic animals.

PMID- 16436894
TI  - Effect of a newly developed charging chamber for the treatment of hypotension
      during hemodialysis.
AB  - We developed a new method of hemodialysis using a charging chamber for treatment
      of hemodialysis patients with hypotension occurring during the latter half of
      hemodialysis (collapse). The purpose of this method was to recover systolic blood
      pressure (BP) by returning a part of blood within the chamber into the body
      circulation when hemodialysis collapse occurred. Using this method, systolic BP
      recovery (DeltaBP) in ten hemodialysis patients (4 males, 6 females, mean age
      66.0 years old) was compared to a control group treated with intravenous
      administration of 20 ml of 10% NaCl. When hemodialysis collapse occurred, 60 ml
      of blood within the chamber in this method and 20 ml of 10% NaCl intravenously in
      the control group were administered and systolic BP was measured 20 minutes
      later. The results showed that DeltaBP using this method was 26.0 mm Hg (ANOVA: p
      = 0.0072), while in the control group it was 30.2 mm Hg (ANOVA: p = 0.0003), and
      there was no significant difference between the systolic BP recovery of both
      groups (paired t test: p = 0.4196).

PMID- 16436895
TI  - Regeneration of canine tracheal cartilage by slow release of basic fibroblast
      growth factor from gelatin sponge.
AB  - We investigated the efficiency of basic fibroblast growth factor (b-FGF) released
      from a gelatin sponge in the regeneration of tracheal cartilage. A 1-cm gap was
      made in the midventral portion of each of 10 consecutive cervical tracheal
      cartilages (rings 4 to 13) in 15 experimental dogs. In the control group (n = 5),
      the resulting gap was left blank. In the gelatin group (n = 5), a gelatin sponge
      alone was implanted in the gap. In the b-FGF group (n = 5), a gelatin sponge
      containing 100 mug b-FGF solution was implanted in the gap. We euthanatized one
      of the five dogs in each group at 1 month after implantation and one at 3 months
      and examined the implant sites macroscopically and microscopically. In the
      control and gelatin groups, no regenerated cartilage was observed in the tracheal
      cartilage gap at 1 or 3 months. The distances between the cartilage stumps had
      shrunk. In the b-FGF group, fibrous cartilage had started to regenerate from both
      host cartilage stumps at 1 month. At 3 months, regenerated fibrous cartilage
      filled the gap and had connected each of the stumps. The regenerated cartilage
      was covered with regenerated perichondrium originating from the host
      perichondrium. Shrinkage of the distance between the host cartilage stumps was
      not observed in the b-FGF group. We succeeded in inducing cartilage regeneration
      in the gaps in canine tracheal cartilage rings by using the slow release of b-FGF
      from a gelatin sponge. The regenerated cartilage induced by b-FGF was fibrous
      cartilage.

PMID- 16436896
TI  - Gastric intramucosal perfusion during descending aortic repair under femoro
      femoral bypass.
AB  - The changes in gastric mucosal perfusion during distal aortic perfusion with
      femoro-femoral bypass (F-F bypass) were assessed by air-automated gastric
      tonometry. A prospective study was performed in six patients who underwent
      descending aortic surgery for aortic aneurysm under F-F bypass with mild
      hypothermia (34 degrees C). Gastric intramucosal pH (pHi) and PaCO2-PgCO2 gap
      (PCO2 gap) were measured. Data are presented as means and standard deviations and
      analyzed by using one-way analysis of variance followed by Scheffe test.
      Perioperative variables of hepatorenal functions are also evaluated. The PCO2 gap
      significantly increased during F-F bypass (3.0 +/- 2.1 mm Hg at control, 14.2 +/-
      5.5 mm Hg during F-F bypass; p = 0.004), indicating abnormal gastric mucosal
      perfusion during F-F bypass. Significantly low pHi was found at weaning from F-F
      bypass (7.35 +/- 0.05 at control, 7.21 +/- 0.10 at weaning; p = 0.009), which
      might be related to progressing systemic metabolic acidosis. No impairment of
      hepatorenal functions was observed after the surgery. Distal perfusion with F-F
      bypass during descending aortic surgery could impair the gastric mucosal
      perfusion, but may have little effect on postoperative visceral dysfunction.

PMID- 16436897
TI  - Deterioration of body oxygen metabolism by vasodilator and/or vasoconstrictor
      administration during cardiopulmonary bypass.
AB  - During cardiopulmonary bypass (CPB), tissue perfusion injury occurs even if
      perfusion pressure is maintained. Although a vasodilator and a vasoconstrictor
      are clinically administered if bypass flow is maintained, they may restore
      perfusion pressure without improving tissue perfusion. We evaluated the influence
      of vasodilators and vasoconstrictors on the whole body during CPB. Fifty-six
      patients with valvular disease who received moderately hypothermic CPB without
      blood transfusion were divided into four groups, depending upon whether a
      vasodilator and/or a vasoconstrictor was administered, and postoperative data
      were compared. Bypass flow and aortic pressure were maintained at 2.4 l/min/m and
      5090 mm Hg. Body weight, dilution, hematocrit level, CPB, and aortic clamp
      duration, blood temperature, bypass flow, perfusion pressure, base excess levels
      during CPB, cardiac index, arterial and mixed venous oxygen pressure, and
      alveolar-arterial oxygen distribution after CPB were comparable among the four
      groups. However, the time to extubation was significantly longer. Blood lactate
      levels, measured for patients returned to the ward, were significantly higher in
      the agent-administered groups than in the no-agent group, whereas blood lactate
      levels on extubation and blood creatinine levels on postoperative day 1 were
      comparable among the groups. Vasodilator and/or vasoconstrictor administration
      during CPB may deteriorate the body oxygen metabolism, which might imply tissue
      perfusion and worsen the complications induced by hypoperfusion during CPB.

PMID- 16436898
TI  - Extracorporeal membrane oxygenation for perioperative cardiac allograft failure.
AB  - The utility of mechanical support in pretransplant stabilization and
      postcardiotomy shock is well established, but its use in perioperative cardiac
      allograft failure (PCAGF) rescue has not been well documented. Ventricular assist
      devices (VADs) have been applied to PCAGF rescue with acceptable results.
      However, studies have not described the results of using extracorporeal membrane
      oxygenation (ECMO) in PCAGF. We evaluated the outcome of PCAGF rescue with ECMO.
      A retrospective review of 204 consecutive heart transplants revealed 19 cases of
      PCAGF requiring ECMO rescue. Donor-, surgery- and ECMO-related variables were
      evaluated for association with operative mortality, success of weaning, and
      survival rate. Transplant recipients included 14 males and 5 females with median
      age of 44.2 years. Weaning rate was 84.2% and survival rate was 52.6%, with
      duration of ECMO support 157 +/- 129 hours. Long ischemic time is a PCAGF risk
      factor (206.8 +/- 96.1 minutes vs. 158.3 +/- 60.8 minutes in non-PCAGF, p <
      0.05). PCAGF etiology included primary graft failure (n = 7); right heart failure
      secondary to pulmonary hypertension, coagulopathy/intraoperative hemorrhage (n =
      7); and sepsis (n = 2). Compared with data from VAD-supported PCAGF, ECMO had a
      better weaning and graft survival rates (p < 0.05). ECMO is another choice for
      PCAGF rescue. It has an acceptable survival rate and may be considered instead of
      VADs as a first-line rescue for PCAGF.

PMID- 16436899
TI  - MRI of the brain and thorax during extracorporeal membrane oxygenation:
      preliminary report from a pig model.
AB  - Early diagnosis of cerebral hypoxic ischemic complications during extracorporeal
      membrane oxygenation (ECMO) is important to guide further treatment. However,
      diagnostic methods available during ECMO are limited, especially in adults and
      older children. Magnetic resonance imaging (MRI) is a sensitive and noninvasive
      method for assessment of vessel patency and brain parenchymal changes, and for
      measurement of brain perfusion. The use of MRI during ECMO has, to our knowledge,
      never been reported. We report the first animal experiment with MRI examination
      during ECMO. After a preliminary test with the mobile ECMO system in the MRI
      environment, a healthy pig was put on venoarterial ECMO, transported to the MRI
      department, and examined with sequences for anatomy and function of the brain and
      thorax. The results showed that the ECMO system was not adversely affected by the
      magnetic field at a distance from the camera where positioning and examination of
      the animal was possible. High-quality anatomical and functional images of the
      brain, heart, and thoracic vessels were acquired. The results suggest that MRI
      may be used for early diagnosis of cranial complications in patients on ECMO. MRI
      may also provide a useful tool for further research on flow dynamics and brain
      perfusion during ECMO.

PMID- 16436900
TI  - Early experience with low-prime (99 ml) extracorporeal membrane oxygenation
      support in children.
AB  - Quick setup is mandatory for cardiopulmonary resuscitation using an
      extracorporeal membrane oxygenation (ECMO) assist device. Our conventional ECMO
      circuit for pediatric patients consists of a centrifugal pump (CX-HP) and
      membrane oxygenator (CX10H). Because of the large priming volume (260 ml), the
      circuit had to be primed with donor blood and required 30 minutes for setup. We
      started to use a low-prime ECMO with small centrifugal pump (HPM-15) and membrane
      oxygenator (MENOX Alpha Cube) for induction of ECMO beginning in 2000. The
      priming volume of this low-prime circuit is only 99 ml. The circuit can be primed
      without donor blood, even in the small patient, and requires only 10 minutes to
      set up. We review our experiences with cardiopulmonary resuscitation for sudden
      cardiopulmonary collapse in pediatric patients, including postcardiotomy
      patients. From 1997 to 2000, 23 patients underwent ECMO support with a
      conventional circuit (group A). From 2000 to 2004, we used low-prime circuit for
      induction of ECMO in 12 patients (group B). After the induction of ECMO with low
      prime circuit, ECMO was converted to conventional heparin-bonded circuit for the
      longer support. The results suggested that the quick induction of ECMO with low
      prime circuit has significant advantages in cardiopulmonary support in pediatric
      patients.

PMID- 16436901
TI  - Direct percutaneous endoscopic jejunostomy placement in a patient with
      intracorporeal left ventricular assist device.
AB  - We present a case involving a patient who required enteral feeding after
      implantation of an abdominally positioned left ventricular assist device. The
      position of the device occupied most of the abdomen, precluding percutaneous
      endoscopic gastrostomy tube placement. However, in the case presented, direct
      percutaneous endoscopic jejunostomy (DPEJ) tube placement was achieved without
      interfering with the intracorporeal device. To our knowledge, there are no
      previous reports in the literature of successful DPEJ placement in a patient with
      an abdominally positioned heart assist device. DPEJ should be considered as a
      long-term enteral feeding route when structural barriers prevent percutaneous
      gastric access.

PMID- 16436902
TI  - Cholestasis induced by parabolan successfully treated with the molecular
      adsorbent recirculating system.
AB  - We describe a case of a 21-year-old male bodybuilder who overdosed on Parabolan
      (trenbolone acetate) because of its anabolic activity. The patient, with no
      previous medical history, experienced pruritus and yellow discoloration of the
      skin and sclerae. Basic biochemical laboratory examination revealed signs of
      cholestasis with a serum bilirubin level of up to 65.5 mg/dl. Because supportive
      medical treatment was ineffective, the patient was treated with the molecular
      adsorbent recirculating system (MARS). Five MARS cycles lasting from 8 to 12
      hours were performed every second day. The procedure was well tolerated by the
      patient and resulted in a sustained relief of pruritus. At the 2-month follow-up
      visit the plasma bilirubin level had decreased to 2 mg/dl.

PMID- 16436905
TI  - In search of intelligent life in the documentation universe: a hospital's journey
      to developing an interdisciplinary computer-based documentation system.

PMID- 16436906
TI  - Podcasting and MP3 players: emerging education technologies.

PMID- 16436907
TI  - Getting the most from your software: using Excel as the poor man's database.

PMID- 16436908
TI  - An exploratory study of predictors of participation in a computer support group
      for women with breast cancer.
AB  - This study examined what characteristics predict participation in online support
      groups for women with breast cancer when users are provided free training,
      computer hardware, and Internet service removing lack of access as a barrier to
      use. The only significant difference between active and inactive participants was
      that active users were more likely at pretest to consider themselves active
      participants in their healthcare. Among active participants, being white and
      having a higher energy level predicted higher volumes of writing. There were also
      trends toward the following characteristics predictive of a higher volume of
      words written, including having a more positive relationship with their doctors,
      fewer breast cancer concerns, higher perceived health competence, and greater
      social/family well-being. Implications for improving psychosocial interventions
      for women with breast cancer are discussed, and future research objectives are
      suggested.

PMID- 16436909
TI  - Coupling the N-CODES system with actual nurse decision-making.
AB  - Nurses must be involved in the development and testing of clinical decision
      support systems if systems that fit into the actual clinical decision-making
      process and the flow of practice are to be designed. This article discusses the
      first trial of N-CODES, the Nurse Decision Support System. This system is
      designed to assist nurses, particularly novices, to make clinical decisions. The
      adequacy of the theoretical framework and selected aspects of the knowledge base
      were examined. Twelve nurses participated. Results indicated that revision of the
      theoretical framework is necessary if it is to be a fair representation of
      nurse's decision-making. The sequencing of information seems appropriate but the
      process of developing the knowledge base must be made more transparent to nurse
      users. After modifications, the next trial will test actual clinical use.

PMID- 16436911
TI  - Computer use in an urban university hospital: technology ahead of literacy.
AB  - The linkage of patient safety and care quality to the implementation of
      computerized information systems assumes that clinical staff are skilled with
      computers. Nurses and nursing support staff increasingly require computers to
      carry out their work. Minimum computer competencies for nurses have been
      identified. The determination of whether the current nursing workforce has
      acquired these competencies remains uncertain. We administered a self-assessment
      survey to nurses and nursing support staff to determine proficiency with computer
      skills they might perform at work. Respondents reported inadequacies in basic and
      work-related computer skills. More than 28% scored themselves as having fair or
      poor proficiency on all skills, and more than 50% as fair or poor on five of 11
      skills. Respondents over age 50 and those graduating before 1984 tended to score
      proficiency lower. Our study suggests that many nurses and nursing support staff
      may not have the minimum computer competencies to effectively and efficiently
      perform their work.

PMID- 16436912
TI  - Electronic health record: implementation across the Michigan Academic Consortium.
AB  - The Michigan Academic Consortium of academic nurse-managed primary care centers
      supported member sites to venture into computer-based advances with the potential
      to improve quality of health services and students' educational experiences. The
      experiences of this consortium as it incorporated electronic health records in
      tandem with an electronic patient management system at several of its member
      sites reveal the benefits and challenges of such an endeavor. The processes of
      selection, adoption, and implementation of the electronic health record are
      discussed in this article. Many lessons learned in the process are discussed.

PMID- 16436913
TI  - Utilizing the language of Jean Watson's caring theory within a computerized
      clinical documentation system.
AB  - The healthcare facility described in the following article is part of an eight
      hospital organization that adopted Watson's Theory of Caring as part of their
      nursing philosophy. According to Watson, this theory is an attempt to find and
      deepen the language specific to nurse caring relations and its many meanings. Yet
      during the implementation of the theory within the setting described, it was
      noted that there was no mechanism in the current documentation system for
      clinical nursing staff to document the patient experience using any language
      specific to the theory. Nursing members recognized an opportunity to develop a
      new context in charting during an extensive clinical documentation system
      upgrade. A discussion of the steps taken and the results within the clinical
      documentation system supporting the newly adopted caring philosophy are
      summarized here.

PMID- 16436917
TI  - Pathological optic-disc cupping.
AB  - PURPOSE OF REVIEW: Pathological optic-disc cupping is most often caused by
      glaucoma, but may be seen in many less-common neuro-ophthalmic conditions. The
      goal of this article is to examine a host of entities causing optic-disc cupping,
      present key differentiating characteristics and pathophysiologies, and outline
      diagnostic approaches. RECENT FINDINGS: Multiple entities not associated with
      elevated intraocular pressure or glaucomatous optic-nerve disease may result in
      pathologic optic-nerve excavation. Even with the photography and imaging of
      today, it is still difficult for the clinician to accurately diagnose other
      causes of optic-disc cupping. Up to 20% of patients may be misdiagnosed and
      treated for glaucoma due to misinterpretation of the optic-disc cupping. Newer
      forms of imaging including optical coherence tomography may assist the clinician
      in decision making. A scrutinizing history, close observation of disc appearance,
      and the vasculature will aid in the diagnosis of glaucoma or other entity of
      optic-disc cupping. SUMMARY: Optic-disc cupping is a consequence of myriad
      disorders. Knowledge of the anatomy and vasculature of the disc is quintessential
      to the understanding of how, why, when, and what type of optic-disc cupping
      occurs in various conditions. Cupping can be seen with neurological processes,
      including benign tumors, which are treatable. Patient history, visual fields
      assessment, and funduscopic findings are the key to unlocking the diagnosis of
      glaucomatous versus nonglaucomatous optic-disc cupping. As clinicians, we must
      remain vigilant and receptive to the findings of potentially ominous forms of
      nonglaucomatous optic-disc cupping.

PMID- 16436918
TI  - Optic-nerve gliomas, chiasmal gliomas and neurofibromatosis type 1.
AB  - PURPOSE OF REVIEW: To review the most recent literature describing the natural
      history and disease progression patterns of optic-pathway gliomas in
      neurofibromatosis type 1 (NF1) patients. To aid in clarifying the current
      treatment patterns and follow-up recommendations. RECENT FINDINGS: Contrary to
      prior documentation, current literature reveals that optic-pathway gliomas in NF1
      can be diagnosed after the age of 6, and may progress until the age of 12. The
      disease progression occurs most frequently in the first two years following
      diagnosis. SUMMARY: Optic-pathway gliomas in NF1 can display a variety of
      manifestations and exhibit an unpredictable disease course. No specific
      characteristics have been found thus far to predict an aggressive compared with
      indolent disease course. Recently primary diagnoses of optic-pathway gliomas have
      been made in children aged six or older, and have been shown to progress until
      the age of 12. Although large-scale studies are required to change current follow
      up recommendations, the data suggest that NF1 patients should be vigilantly
      evaluated for optic-pathway gliomas past the age of 12.

PMID- 16436919
TI  - Restoration of accommodation.
AB  - PURPOSE OF REVIEW: This review examines the current status of accommodation
      restoration concepts with reference to the recent, published peer-reviewed
      literature with an emphasis on physiological aspects of accommodation and
      presbyopia. RECENT FINDINGS: The mechanisms of accommodation and the causes of
      presbyopia are described. The physiological amenability of the accommodative
      structures in the presbyopic eye to accommodation restoration is discussed.
      General theoretical concepts of accommodation restoration are introduced. The
      methods that have been used to assess accommodation restoration, including the
      use of animal models, drug stimulated accommodation, subjective near-vision tests
      and objective measurements, are reviewed. SUMMARY: While physiological and
      clinical evidence supports the notion that accommodation can be restored to the
      presbyopic eye, progress in this potentially exciting area is hindered by the
      scarcity of good, large-scale clinical studies using objective measurement
      techniques to evaluate the outcomes of accommodation restoration concepts.

PMID- 16436920
TI  - Contrast sensitivity: determining the visual quality and function of cataract,
      intraocular lenses and refractive surgery.
AB  - PURPOSE OF REVIEW: This review provides an update of recent advances in
      understanding the quality and functional significance of contrast sensitivity for
      the clinician regarding cataract, intraocular lenses and refractive surgery that
      goes beyond the measurement of visual acuity. RECENT FINDINGS: New American
      National Standards Institute standards for contrast sensitivity based on linear
      sine-wave gratings are discussed that promise rapid advances of understanding and
      quantifying visual quality and function by unifying clinical results reported
      using contrast sensitivity. Increased sensitivity of linear sine-wave gratings
      over proposed bull's-eye radial gratings is discussed. Digital-image-processing
      software uses contrast sensitivity data to process images to help understand the
      quality of what the patient sees. Contrast sensitivity measurement is compared
      with wavefront aberrometry. Contrast sensitivity measures the total visual system
      quality in terms of contrast, whereas wavefront aberrometry measures the optical
      quality in terms of spatial distortion. Both measurements are needed to more
      fully understand the quality of vision. SUMMARY: Recent advances provide the
      clinician with an awareness of why the new contrast-sensitivity standards are
      based on linear sine-wave gratings and how image-processing software can be used
      to better understand the quality of functional vision of the patient.

PMID- 16436921
TI  - Recent developments in pseudophakic dysphotopsia.
AB  - PURPOSE OF REVIEW: Photic phenomena associated with intraocular lenses can
      degrade visual performance following intraocular lens implantation. Postoperative
      dysphotopsia introduces glare, halos, starbursts and shadows in a small number of
      patients. Understanding the optical mechanisms behind the introduction of these
      artifacts can lead to improved lens design and a reduction in the deleterious
      effects of stray light. This review looks at the improvement efforts of recent
      years to illustrate the systematic hunt for lens problems. RECENT FINDINGS:
      Improvements in edge designs have diminished the effects of positive
      dysphotopsia. However, negative dysphotopsia remains poorly understood and a
      variety of lens designs and materials can cause negative dysphotopsia. In other
      efforts, a testing procedure has been developed to improve understanding of the
      visual percept of a patient suffering dysphotopsia. This test should enlighten
      practitioners to the deficits their patients face and provide clues to the root
      causes of the problems. SUMMARY: Intraocular lenses can introduce stray light
      artifacts into the eye. These artifacts manifest themselves as glare, halos,
      starbursts and shadows. While positive dysphotopsia (glare, halos and starbursts)
      has been largely attributed to edge effects of the implant, negative dysphotopsia
      remains somewhat mysterious and appears to be more related to the patient's
      anatomical structure than to specific lens designs or materials.

PMID- 16436922
TI  - Capsular tension rings and related devices: current concepts.
AB  - PURPOSE OF REVIEW: To discuss current designs, indications, contraindications and
      controversies pertaining to capsular tension devices. RECENT FINDINGS: Capsular
      tension rings and other newer endocapsular support devices have become
      increasingly important in the management of zonular weakness during cataract
      extraction. They have been found to improve both intraoperative support during
      phacoemulsification and postoperative intraocular lens centration. Since the
      introduction of the original capsular tension rings in 1991, there has been a
      progressive evolution of this device to help deal with profound zonular weakness.
      These newer devices, which permit scleral-suture fixation, include the modified
      capsular tension ring and the capsular tension segment. SUMMARY: Continual
      advances in capsular tension device technology have allowed for increased safety
      and efficacy in performing cataract surgery in patients with zonular weakness
      with newer devices being evolved to manage more profound cases.

PMID- 16436923
TI  - Capsular staining: recent developments.
AB  - PURPOSE OF REVIEW: This paper reviews the recent literature regarding anterior
      capsular staining. RECENT FINDINGS: Safety and efficacy of dyes used in
      facilitating visualization of the anterior capsule during phacoemulsification are
      compared. Advantages of using different techniques for injection of the dyes are
      discussed. SUMMARY: Trypan Blue and Indocyanine Green appear to be most effective
      in staining the anterior capsule with the highest safety profile. Injection
      strategies should be aimed at reducing uncontrolled dispersion especially into
      the vitreous.

PMID- 16436924
TI  - Posterior capsule opacification.
AB  - PURPOSE OF REVIEW: This paper assesses the factors that contribute to the
      formation of an effective capsular bend as a deterrent to posterior capsule
      opacification. Its goal is to assist the practicing ophthalmologist in separating
      current understanding of this process from various working models previously
      proposed. RECENT FINDINGS: While a square-edge design appreciably improves
      resistance to posterior capsule opacification, significant factors remain under
      the control of the surgeon. These factors combine to form the physical and
      psychological barrier of a capsular bend. Innovative digital imaging has shown
      lens epithelial cell migration, allowing for a more rapid assessment of posterior
      capsule opacification resistance. A three-piece intraocular lens allows for full
      360 degree capsular bend formation surrounding the optic edge; some single-piece
      designs may inhibit capsular bend formation. Decreasing, but not eliminating, the
      surviving lens epithelial cell population may diminish capsular bend strength,
      which may decrease resistance to posterior capsule opacification in the face of a
      regenerating cortex. All demographic features of clear/refractive lens exchange
      suggest higher rates of posterior capsule opacification than with standard
      cataract surgery. SUMMARY: The quality of capsular bend formation will determine
      how resistant an intraocular lens will be to posterior capsule opacification as a
      consequence of regenerating cortex. As refractive lens exchange and new
      accommodating intraocular lens designs become more popular, the problems of
      regenerating cortex will increase in magnitude.

PMID- 16436925
TI  - Pediatric cataract surgery.
AB  - PURPOSE OF REVIEW: Pediatric cataract surgery remains a very important and
      difficult problem to manage. While dramatic advances have occurred in this field
      over the past 10 years, some technical aspects of surgery, changing refraction
      and functional outcome continue to pose significant problems. The aim of the
      present review is to update the reader on advances reported on the topic during
      the past year. RECENT FINDINGS: Manual capsulorhexis still remains a gold
      standard for the successful outcome of pediatric cataract surgery. Primary
      management of the posterior capsule is mandatory depending on the age of the
      child at surgery. Primary implantation of the intraocular lens after cataract
      removal is gaining popularity even in infants and young children. Short-term
      results of single-piece Acrysof in pediatric eyes are encouraging. Predicting
      axial growth and the refractive change that accompanies it is one of the major
      challenges for long-term care of children after surgery. The evaluation of rate
      of axial growth and its correlation with age at surgery, laterality,
      aphakia/pseudophakia and visual-axis obscuration is a positive step in the right
      direction. Despite satisfactory technical outcomes, the functional outcomes
      remain unpredictable. SUMMARY: With refinements in surgical techniques,
      improvisation of intraocular lenses and better understanding of growth of the
      pediatric eye, in the coming years intraocular lens implantation is likely to
      become an established mode of treatment of children even in the youngest age
      group.

PMID- 16436926
TI  - Update on bimanual microincisional cataract surgery.
AB  - PURPOSE OF REVIEW: The purpose of this article is to highlight the major issues
      associated with bimanual microincisional cataract surgery and to review the
      recent literature addressing this subject. RECENT FINDINGS: Bimanual
      microincisional cataract surgery has been performed successfully using all of the
      major phacoemulsification platforms. Technological advances in ultrasound power
      management and fluidics have improved the safety profile and efficiency of this
      technique. New intraocular-lens designs and surgical maneuvers permit intraocular
      lens insertion through corneal incisions measuring 2 mm or less. Clinical results
      achieved with bimanual microincisional cataract surgery and new microincision
      lenses are comparable to those obtained with conventional coaxial
      phacoemulsification and established intraocular lenses. SUMMARY: Bimanual
      microincisional cataract surgery is a promising surgical technique that continues
      to grow as phacoemulsification technology and intraocular-lens designs evolve.

PMID- 16436927
TI  - Endophthalmitis and incision construction.
AB  - PURPOSE OF REVIEW: The relationship between endophthalmitis after cataract
      extraction and type of incision has been under debate lately. In particular,
      clear corneal incisions have been connected with an increased incidence of
      postoperative endophthalmitis. This review discusses recent reports within this
      area. RECENT FINDINGS: Experimental studies have demonstrated the poor integrity
      of a clear corneal incision under certain circumstances. A relationship between
      wound leakage the day after surgery and endophthalmitis has also been reported.
      Some large studies have shown an increase of endophthalmitis that in time
      coincide with the increasing use of clear corneal incision. One earlier
      randomized controlled study showed a higher incidence of endophthalmitis after
      clear corneal incision compared with superior incision. Other case series have
      shown an equal distribution of endophthalmitis between surgeries using different
      types of incision. Some studies point to the multifactorial nature of
      endophthalmitis and the importance of every step from antiseptic surgical field
      to postoperative treatment. SUMMARY: There is no conclusive evidence of the
      relationship between clear corneal incision and endophthalmitis. It seems,
      however, that in certain situations clear corneal incision may play a role in the
      occurrence of endophthalmitis.

PMID- 16436928
TI  - A light adjustable lens with injectable optics.
AB  - PURPOSE OF REVIEW: Technology exists today that could permit refractive precision
      unheard of at the present time plus the correction of higher-order aberrations
      and restoration of accommodation in presbyopic adults. RECENT FINDINGS: With the
      light adjustable lens, after surgery, the shape of the lens can be customized to
      treat spherical, cylindrical and other higher-order aberrations. The posterior
      surface of the lens can be adjusted to create both refractive multifocality and
      diffractive bifocality. It can be made out of a variety of materials, some of
      which can be injected into the capsule, filling it, thus replicating the original
      shape of a crystalline lens. While the current technique of bag filling does
      permit the less viscous materials to leak out of the bag this is a solvable
      problem. For example, a disc can fill an ordinary-sized capsulorrhexis opening,
      allowing removal of the cataract using standard techniques and filling behind
      this disc. Also the material, once injected, could be polymerized. Posterior
      capsule opacification is also potentially solvable with devices that completely
      destroy lens epithelial cells or through a polymerization process of the new lens
      material in which the reaction destroys the capsular cells and actually binds to
      the capsule. SUMMARY: It is apparent that light adjustable lenses plus injectable
      technology, and multifocality can produce precise refractive correction and,
      hopefully, the type of accommodative range that we take for granted when we are
      young. Combining these technologies with a lens material that behaves like a
      crystalline lens of a 25 year old could precisely return near and distance vision
      to older adults.

PMID- 16436929
TI  - Advances in microincision cataract surgery intraocular lenses.
AB  - PURPOSE OF REVIEW: This paper reviews the recent developments in microincision
      cataract surgery intraocular lenses. RECENT FINDINGS: Seven intraocular lenses
      are currently available for implantation through sub-2.0-mm incision. From the
      intraocular lenses available, two microincision cataract surgery intraocular
      lenses were included in clinical studies and their results were reviewed. The
      available lenses were implanted through a clear corneal incision of 1.5-1.9 mm
      and showed excellent biocompatibility. The behavior of the microincision cataract
      surgery in vivo is similar to the conventional lenses in terms of optical quality
      and retinal image quality. The clinical results of microincision cataract surgery
      intraocular lenses such as Acri. Smart 48S showed that a certain degree of
      pseudoaccommodation could be achieved with this lens. SUMMARY: Cataract removal
      through sub-2.0 mm incision is possible with implantation of microincision
      cataract surgery intraocular lenses through the same undilated incision. The
      current technique allows cataract removal through 1.7 mm and the available
      microincision cataract surgery intraocular lenses showed optical quality and
      biocompatibility similar to conventional intraocular lenses.

PMID- 16436930
TI  - The Implantable Miniature Telescope for macular degeneration.
AB  - PURPOSE OF REVIEW: The function is described of the Implantable Miniature
      Telescope, which is completing clinical development for bilateral end-stage
      macular degeneration, and 6-month results of the Phase II/III IMT002 prospective,
      multicenter study are presented. Multispecialty patient management and
      implications of the study's findings are discussed. RECENT FINDINGS: No medical
      treatments are currently available for bilateral end-stage age-related macular
      degeneration (atrophic or disciform scar age-related macular degeneration). The
      visual prosthetic device discussed in this update is implanted in the posterior
      chamber to reduce the impact of the scotomata on the patient's central vision.
      The goal of treatment is to improve the patient's ability to perform everyday
      activities and participate in roles and hobbies that impact their quality of
      life. Patients implanted with the device experienced clinically significant gains
      in visual acuity and quality of life at 6 months. In total, 89% gained two or
      more lines of best-corrected near or distance visual acuity. The device was
      generally safe and well tolerated. The surgical technique is important to
      minimize surgically related reduction in endothelial cell density. SUMMARY: This
      age-related macular degeneration visual prosthesis has been shown to improve
      visual acuity and quality of life for the bilateral end-stage age-related macular
      degeneration patient population that at present has no other acceptable options.
      Endothelial cell density from baseline to 6 and 12 months after device
      implantation was reduced due to trauma from the surgical procedure, but was
      compatible with a healthy cornea. Meticulous surgical technique and a
      comprehensive, multispecialty approach to preoperative and postoperative patient
      management are essential for successful outcomes.

PMID- 16436931
TI  - Phakic intraocular lenses.
AB  - PURPOSE OF REVIEW: Laser in-situ keratomileusis has been tremendously successful
      in treating patients with mild and moderate ametropias. For patients with high
      degrees of refractive error, however, phakic intraocular lenses provide superior
      quality of vision without the risk of corneal ectasia. Early international
      results, as well as United States Food and Drug Administration clinical trials,
      have demonstrated the early safety and efficacy of phakic intraocular lenses.
      Nevertheless, long-term corneal endothelium cell density and crystalline lens
      clarity remain a concern. RECENT FINDINGS: Several new studies demonstrate the
      superior visual outcomes of phakic intraocular lenses over laser in-situ
      keratomileusis in patients with moderate and high myopia, particularly in the
      areas of visual quality and contrast sensitivity. New anterior segment imaging
      and measurement technologies have provided valuable information about in-vivo
      structure and function, with and without phakic lens implants. More is being
      learned about long-term endothelial cell stability and cataract formation,
      particularly in relation to implant positioning. New applications of phakic
      intraocular lenses in presbyopia and in other conditions are being explored.
      SUMMARY: Once plagued by complications and marginal outcomes, improved designs of
      phakic intraocular lenses are providing increasing safety and efficacy for the
      correction of severe ametropias. Long-term concerns with endothelial cell loss
      remain, but recent data suggest stabilization with time. Proper sizing and
      positioning are important and increasingly achievable with new imaging
      modalities. With continued research and experience, phakic intraocular lenses are
      becoming an invaluable addition to the mainstream refractive surgery
      armamentarium.

PMID- 16436932
TI  - Current world literature.

PMID- 16436933
TI  - Why do we need new and better antidepressants?
AB  - The range of available antidepressants is reviewed in relation to mechanisms of
      action and the evidence of efficacy in general and efficacy in severe depression
      in particular. In studies investigating efficacy in major depressive disorder,
      not all antidepressants have been shown to have clear-cut efficacy in severe
      depression. Here, the minimum standards for the necessary methodology to
      investigate efficacy in severe depression are reviewed and the methods that are
      needed to establish efficacy as a superior antidepressant or as an antidepressant
      with a faster than expected response are suggested. A review of the mechanisms of
      action of different antidepressants is accompanied by a critical review of the
      properties of an antidepressant likely to achieve either efficacy in severe
      depression or the status of a superior antidepressant.

PMID- 16436934
TI  - Biological rhythm disturbances in mood disorders.
AB  - From earliest times, psychiatrists have described biological rhythm disturbances
      as characteristic of mood disorders. The present flourishing of circadian biology
      has revealed the molecular basis of 24-h rhythmicity driven by 'clock' genes, as
      well as the importance of zeitgebers (synchronisers). Winter depression was first
      modelled on regulation of animal behaviour by seasonal changes in daylength, and
      led to application of light as the first successful chronobiological treatment in
      psychiatry. Light therapy has great promise for many other disorders (e.g. sleep
      wake cycle disturbances in Alzheimer's dementia, bulimia, premenstrual disorder,
      depression during pregnancy) and, importantly, as an adjuvant to antidepressant
      medication in major non-seasonal depression. The pineal hormone melatonin is also
      a zeitgeber for the human circadian system, in addition to possessing direct
      sleep-promoting effects. Chronobiology has provided efficacious non
      pharmaceutical treatments for mood disorders (such as sleep deprivation or light
      therapy) as well as novel approaches to new drugs (e.g. agomelatine).

PMID- 16436935
TI  - Pharmacology of a new antidepressant: benefit of the implication of the
      melatonergic system.
AB  - The limitations of current antidepressant medications merit the exploration of
      alternative agents with novel antidepressant mechanisms of action. The
      established clinical finding that desynchronization of internal rhythms plays an
      important role in the pathophysiology of depressive disorders has stimulated the
      idea that resetting normal circadian rhythms may have antidepressant potential.
      Recent experiments using the novel melatonin receptor agonist and serotonin 2 (5
      HT2c) receptor antagonist agomelatine (S20098; N[2-(7-methoxy-1-naphthyl)ethyl]-
      acetamide) revealed a notable chronobiotic activity and clear antidepressant-like
      effects in a variety of preclinical models. Binding studies performed in vitro
      proved that agomelatine is a high-affinity agonist at both the melatonin MT1 and
      MT2 receptor types. In addition, these studies revealed that agomelatine, in
      contrast to melatonin, blocks 5-HT2c receptors with significant affinity.
      Antagonism of 5-HT2c receptors is reported for various established antidepressant
      compounds. The antidepressant properties of agomelatine are thus based on its
      melatonergic actions and 5-HT2c receptor antagonism.

PMID- 16436936
TI  - Clinical efficacy of agomelatine in depression: the evidence.
AB  - Despite the advances of recent decades, there is still an urgent need for
      antidepressants with improved efficacy, safety and tolerability. Agomelatine is a
      new antidepressant with an innovative pharmacological profile. It is the first
      melatonergic antidepressant, and is a potent agonist of melatonin receptors (MT1
      and MT2) with 5-HT2C antagonist properties. The efficacy of 25 mg/day agomelatine
      in treating major depressive disorder (MDD) has been demonstrated in a number of
      placebo-controlled studies. Evidence of improvement in depressive symptoms was
      observed in a dose-ranging study in which 25 mg/day agomelatine was significantly
      better than placebo, whatever the rating scale used (Hamilton Rating Scale for
      Depression, Clinical Global Impression, and Montgomery-Asberg Depression Rating
      Scale). These results have been confirmed in two similarly designed placebo
      controlled studies. Agomelatine also produces a significant improvement in
      anxiety compared to placebo, according to Hamilton Rating Scale for Anxiety
      scores. The efficacy of agomelatine has been studied in subpopulations with more
      severe depression, demonstrating its efficacy in these difficult-to-treat
      patients. In view of the available data on agomelatine, this antidepressant can
      be regarded as an innovative treatment for MDD patients, offering a new approach
      in the management of depressed patients.

PMID- 16436937
TI  - Sleep disturbances and depression: a challenge for antidepressants.
AB  - Sleep disturbances are commonly experienced by depressed patients, and
      abnormalities of sleep architecture are among the most robust psychobiological
      correlates of major depression. Most antidepressants alter the physiological
      patterns of sleep and eventually improve sleep symptoms, along with other
      symptoms of depression. However, many antidepressants also have unwanted adverse
      effects on sleep, notably by causing or worsening insomnia, daytime sleepiness or
      sedation. This article briefly reviews the biology of sleep, the sleep
      disturbances associated with depression, and the therapeutic and adverse effects
      of antidepressants on sleep. It also describes a novel antidepressant,
      agomelatine, which improves symptoms of depression and rapidly relieves sleep
      complaints without sedative effects.

PMID- 16436938
TI  - Efficacy and tolerance profile of agomelatine and practical use in depressed
      patients.
AB  - Agomelatine is a new agent with a unique pharmacological profile, as the first
      melatonergic antidepressant. Its antidepressant efficacy has been demonstrated in
      the treatment of major depressive disorder (MDD) at a dose of 25 mg/day.
      Expectations from antidepressant therapies now go beyond efficacy alone, to
      include advantages in tolerability and safety. Due to its pharmacological
      profile, agomelatine does not induce the side-effects typical of other therapies,
      such as selective serotonin reuptake inhibitors (i.e. gastrointestinal disorders,
      weight gain, serotonergic syndrome and insomnia). Moreover, a placebo-controlled
      trial in MDD comparing the effects of agomelatine and venlafaxine on sexual
      dysfunction (another significant side-effect with current antidepressant
      medications) indicated the very favourable profile of agomelatine; in the same
      study, there was similar antidepressant efficacy in the same two groups. A double
      blind, placebo-controlled trial investigating the effect of abrupt cessation of
      treatment demonstrated the absence of discontinuation symptoms with agomelatine,
      which was in contrast with the results observed with paroxetine. The ability of
      an antidepressant to relieve sleep complaints with no sedative effects is a key
      advantage because sleep complaints are a major presenting feature of depression.
      Again due to its unique pharmacological profile, agomelatine has been shown to
      positively influence disturbed circadian rhythms in depressed patients by
      significantly improving all phases of disturbed sleep and the overall quality of
      sleep, with a favourable impact on daytime alertness. In conclusion, experience
      with agomelatine across a range of clinical studies suggests that this compound
      offers a novel approach to the treatment of depression combining efficacy, even
      in severe depression, with an extremely favourable side-effect profile and sleep
      regulation. These properties give agomelatine a definite clinical advantage in
      the treatment of depression.

PMID- 16436939
TI  - A new, objective radiographic classification system for the assessment of
      treatment results in developmental dysplasia of the hip.
AB  - The new, objective radiographic classification system for the assessment of
      treatment results in developmental dysplasia of the hip includes three
      quantitative parameters: centre-edge angle of Wiberg, acetabular angle of Sharp
      and the centre-trochanter distance. Each parameter is divided into three
      subgroups and assigned a point score (0, 1 and 2) according to their previously
      determined values. Besides this, three corrective items on the existence of
      middle/posterior acetabular deficiency, secondary operation and
      resubluxation/redislocation are added to the classification system and in the
      presence of any of these items, one point for each item is extracted from the
      total points. A total of five or six points represents a satisfactory outcome and
      less than five points, an unsatisfactory outcome. The new system was found to
      have adequate intraobserver and interobserver agreement levels. It was also
      observed that, the gold standard Severin system could lead the raters to obtain
      somewhat more optimistic results with respect to the new system before and after
      skeletal maturity. It was concluded that the present system could evaluate both
      the final radiographic status of the hip and the success or failure of the
      primary treatment and could be capable of leading orthopaedic surgeons to speak
      the same language while assessing radiographic results in developmental dysplasia
      of the hip.

PMID- 16436940
TI  - Does Dega osteotomy increase acetabular volume in developmental dysplasia of the
      hip?
AB  - Whether acetabular volume increases or decreases after acetabular Dega osteotomy
      is not known. The purpose of this study is to determine the effect of Dega
      osteotomy on the volume of the acetabulum in patients with developmental
      dysplasia of the hip. Nine hips of seven patients with developmental dysplasia of
      the hip that have undergone Dega osteotomy were included in the study. The
      acetabular index, acetabular depth, and acetabular volume of each hip were
      calculated before and after surgery. Magnetic resonance imaging was used for the
      measurement of the acetabular volume. The difference between the preoperative and
      postoperative values of acetabular index, acetabular depth, and acetabular volume
      was statistically significant. We conclude that Dega acetabular osteotomy
      increases the volume of the acetabulum.

PMID- 16436941
TI  - Osteotomy does not improve early outcome after slipped capital femoral epiphysis.
AB  - We performed a retrospective, nonrandomized cohort study of unilateral, chronic,
      severe, stable slipped capital femoral epiphysis comparing five girls and five
      boys who underwent in-situ screw fixation alone with five girls and five boys who
      underwent in-situ screw fixation combined with staged flexion intertrochanteric
      femoral osteotomy to restore proximal femoral alignment. Functional outcome was
      measured by the Harris hip score, with 20% selected as a goal for improvement in
      functional outcome after corrective osteotomy. While flexion intertrochanteric
      femoral osteotomy improved hip range of motion, we found no significant
      difference in functional outcome between the two groups at early follow-up. This
      is a level 3 evidence study.

PMID- 16436942
TI  - Consequences of diagnostic delays in slipped capital femoral epiphysis.
AB  - Delay in diagnosis of slipped capital femoral epiphysis has important
      implications with regard to slip severity and long-term hip outcomes. The aims of
      this review were to identify the incidence of delayed diagnosis of slipped
      capital femoral epiphysis in the hospital to which the authors are affiliated,
      and the causes for such delays. A retrospective review was conducted of all
      patients admitted to the Women's and Children's Hospital in Adelaide between
      January 1997 and October 2004 with a diagnosis of slipped capital femoral
      epiphysis. The inpatient and outpatient medical records for each patient were
      analysed to clarify the history of presentation and identify those patients with
      a delayed diagnosis. All radiographs were reviewed and the severity of the slip
      graded according to Southwick's classification. One hundred and two patients were
      included in this review, of which 20 had a delayed diagnosis and 25 a late
      presentation. Of the 20 (19.6%) patients who had a delayed diagnosis in this
      series, a minimum of 2 weeks elapsed between presentation to a health
      professional and diagnosis of slipped capital femoral epiphysis. Eight patients
      had seen their local doctor but the diagnosis was not made. The remaining 12
      patients with delayed diagnosis had not seen a medical practitioner and had self
      referred to a chiropractor or a physiotherapist. All of these patients underwent
      hip manipulation prior to diagnosis. There was a significant relationship between
      delay in diagnosis and an increased slip severity, when compared with both the
      remainder of this series and the late presentation group. Knee or distal thigh
      pain in slipped capital femoral epiphysis remains the commonest pitfall in
      diagnosis for local doctors, as well as mild slips being missed on radiograms by
      inexperienced surgeons or radiologists. An increasing presentation of adolescents
      with this disorder to allied health professionals for initial management warrants
      a broader education strategy than has been previously advocated. Slipped capital
      femoral epiphysis remains an enigmatic disorder; consequently delayed diagnosis
      of this condition is not likely to disappear. Despite this, the medical community
      must strive toward early diagnosis through continued education and vigilance.

PMID- 16436943
TI  - Outcomes of new pogo-stick brace for Legg-Calve-Perthes' disease.
AB  - In 1992, the authors developed a non-weightbearing unilateral ambulatory hip
      abduction brace, which was named the new pogo-stick brace for unilateral Legg
      Calve -Perthes' disease. The hip abduction angle of the new pogo-stick brace was
      adjustable 45 degrees . The advantage of this brace was that even in the sitting
      position, the hip abduction angle was maintained. Twenty patients were treated
      with unilateral LCPD using the new pogo-stick brace. In the Catterall
      classification, one patient was classified as group 2, 17 as group 3, two as
      group 4. In Herring classification, one patient was classified as group A, 17 as
      group B, two as group C. Ultrasonography was performed to determine containment
      of the hip joints, and the abduction angle of the new pogo-stick brace was
      adjusted to get better containment, every 2 months. Mose's and acetabular head
      index methods were used for radiographic evaluation, and classified into good,
      fair and poor groups both at the primary healing and at the final follow-up.
      Total evaluation was defined as worse group between Mose's method and acetabular
      head index method. The average time from onset of disease to the primary healing
      was 25 months. The average bracing period was 21 months. The average follow-up
      period was 94 months. At the final follow-up appointment, patients who were
      classified into good and fair groups were 85% in Mose's method, 95% in acetabular
      head index method, 85% in total evaluation. In Stulberg classification, the total
      number of patients who were classified into classes I and II was 85%. The outcome
      of the new pogo-stick brace was not worse than that of any other treatment
      method, and was better than that of other unilateral ambulatory braces.

PMID- 16436944
TI  - Distal hamstring lengthening in cerebral palsy: the influence of the proximal
      aponeurotic band of the semimembranosus.
AB  - We undertook a prospective review of 24 children with spastic diplegia treated by
      distal hamstring fractional lengthening at the Sheffield Children's Hospital. In
      14 children (24 limbs) the correction achieved (popliteal angle) was inadequate
      and in these patients in the operating room a further correction was attained by
      dividing a tight band palpated in the substance of the semimembranosus muscle.
      Under general anaesthetic (preoperatively) the popliteal angle (a degrees ) was
      measured using a goniometer, then again (b degrees ) following distal hamstring
      fractional lengthening and finally (c degrees ) after surgically dividing the
      tight band. The mean preoperative popliteal angle (a degrees ) in all 24 limbs
      was 65 degrees (52-90). Following the standard hamstring fractional lengthening
      it (b degrees ) measured 37 degrees (35-50) and after division of the tight band
      it (c degrees ) measured 15 degrees (10-20). The reduction in popliteal angle
      following release of the tight band (proximal aponeurosis) was statistically
      significant (P<0.05). We undertook a cadaveric examination of 22 lower limbs and
      confirmed in all the cases that this band was the proximal aponeurosis of the
      semimembranosus muscle. The proximal aponeurosis is a well defined band located
      at the anterior aspect of the semimembranosus muscle where it arises from the
      tendon of the proximal attachment. It is separate from the distal aponeurosis.
      Division of the proximal aponeurosis during fractional lengthening of the distal
      hamstring in patients with cerebral palsy results in a significant reduction in
      the flexion deformity.

PMID- 16436945
TI  - Radiographic outcome of soft-tissue surgery for hip subluxation in non-ambulatory
      children with cerebral palsy.
AB  - This study reviewed radiographs of non-ambulatory spastic tetraparetic cerebral
      palsy patients who underwent soft tissue hip surgery to address hip subluxation.
      Patients were under 10 years of age at surgery, had limited hip motion, and
      radiographic subluxation. At an average 7.4 years postoperatively, hips had a
      migration percentage in the normal range (0-15%) in 58 of 70 cases (83%). Hips
      with preoperative subluxation between 30 and 49% had a normal migration
      percentage in 18 of 21 cases (81%), and those over 50% in three of seven (43%) of
      cases. Soft tissue surgery alone, even in cases of moderate hip subluxation, can
      result in long-term radiographic hip stability.

PMID- 16436946
TI  - Preparation of massive anti-infective reconstituted bone xenograft and related
      studies.
AB  - The purpose of this study was to develop a new type of anti-infective bone
      transplantation material. A massive anti-infective reconstituted bone xenograft
      with calcium phosphate drug core (CPC-MARBX) was prepared; a drug delivery
      profile and capability of repairing large segmental infected bony defect were
      characterized with drug delivery tests and in the rabbit model with large
      segmental infected bony defect. CPC-MARBX was produced with relatively simple
      procedures. The duration of the drug delivery was about 25 days in vitro and 30
      days in vivo. The infected bony defect was successfully repaired with good
      healing. CPC-MARBX is readily available and can be applied in repairing the large
      segmental infected bony defect.

PMID- 16436947
TI  - In-vitro mechanical impacts on calves' proximal femurs: significance of
      mechanical weakening of the femoral head in the etiology of Perthes disease in
      children.
AB  - Experimental research was conducted to determine the effects of mechanical forces
      on the hip joint in the etiology of Perthes disease in children. The authors
      aimed to identify areas of lower resistance to mechanical forces in a growing
      femoral head. Calves' femurs, used as experimental models, were repeatedly
      subjected to mechanical impacts. The results showed that the areas most
      susceptible to trauma were the layers of immature bone located underneath the
      epiphyseal growth zone and underneath the growth plate. The authors conclude that
      blood vessels in these areas are highly vulnerable to mechanical damage, and the
      resulting impairment of blood flow to the femoral head leads to the development
      of Perthes disease in children.

PMID- 16436948
TI  - Incidence of physeal injuries in Japanese children.
AB  - Although epidemiological studies on epiphyseal injury have been reported, such
      studies have not been made systematically in Japan. In this study, we examined
      the incidence of epiphyseal injury in paediatric patients treated at five general
      hospitals and three private clinics. We treated the patients with limb injuries
      between January 1992 and December 1997, and reviewed them at least 18 months
      after the original injuries. The original radiograms and the completed case
      records were classified according to age and sex of the injured children, site of
      the fracture, type of treatment, and its complications. Epiphyseal injuries
      accounted for 17.9% of all paediatric fractures. The most frequently injured
      epiphysis was the phalanges of hands, 21.9% of all physeal injuries. Salter
      Harris type I accounted for 28.6% of physeal injuries; type II (60.9%) revealed
      the largest number of cases in this study, compared with type III (6.7%) and type
      IV (3.7%). Type V was not recognized. Most physeal injuries were treated
      conservatively. Either weight-bearing joints or elbow joints were treated
      surgically. Complications of physeal injuries were seen in seven cases. Five
      cases involved the upper limb, and the other two cases involve the lower limb.
      Although deformity or malfunction caused by physeal injuries was remained, only
      one case needed a corrective osteotomy. Other six cases revealed a fair
      prognosis.

PMID- 16436949
TI  - Undisplaced femoral neck fractures in children have a high risk of secondary
      displacement.
AB  - Femoral neck fractures in children are rare and known to have a high complication
      rate (e.g. femoral head necrosis, persistent deformities, and pseudarthrosis).
      While open reduction and internal fixation is the treatment of choice for
      displaced fractures, non-operative treatment methods have been proposed if the
      fracture is undisplaced. Three consecutive patients aged 11, 14 and 16 years with
      undisplaced femoral neck fractures were seen at our institutions and primarily
      treated with the recommendation of non-weightbearing and minimal flexion until
      consolidation. All three cases showed secondary displacement within the first 6
      weeks. A second minor indirect trauma caused displacement in one case; in the
      other two cases, no further trauma had occurred. All three fractures healed
      uneventfully following reduction and osteosynthesis. Undisplaced femoral neck
      fractures treated non-operatively evidently bear the risk of secondary
      displacement. The observations in these patients suggest that primary internal
      stabilization, even of undisplaced femoral neck fractures in children, should be
      considered.

PMID- 16436950
TI  - Sonographic classification of idiopathic clubfoot according to severity.
AB  - Our purpose was to develop a sonographic technique for clubfoot examination using
      measured angles to establish a classification system according to severity.
      Ultrasonography of 24 newborns with 32 clubfeet and 13 newborns with 22 normal
      feet was performed and measurements obtained. Analysis of components of variance
      was conducted. Patients with clubfeet showed higher dispersion in 95% confidence
      intervals for all angles than did patients with normal feet. A sonographic
      classification system was established: IIa, slight clubfoot; IIb, moderate
      clubfoot; IIc, severe clubfoot; IId, very severe clubfoot. Sonographic findings
      can be used to objectively assess various degrees of clubfoot severity.

PMID- 16436951
TI  - Comparison of posterior and anterior pelvic osteotomy for bladder exstrophy
      complex.
AB  - To compare the correction and maintenance of the pelvic ring after pelvic
      osteotomy in bladder exstrophy complex, we analyzed all cases performed at our
      institution. Posterior osteotomy was performed in six patients; anterior or
      combined osteotomy was performed in four patients. Patients who underwent
      posterior osteotomy had a mean pubic approximation of 37.3%. The mean was 62.8%
      in patients undergoing anterior or combined osteotomy. This difference was
      statistically significant (P<0.05 ). The mean recurrence of separation in pubic
      diastasis was 90.5% for posterior osteotomy and 41.6% for anterior or combined
      osteotomy. These results indicate that an anterior or combined pelvic osteotomy
      corrects and maintains the pelvic ring with a bladder exstrophy complex more
      effectively than a posterior pelvic osteotomy.

PMID- 16436952
TI  - Limb lengthening in fibular hemimelia type II: can it be an alternative to
      amputation?
AB  - The purpose of our study was to analyze limb lengthening in fibular hemimelia
      type II. Ten patients underwent 16 tibia lengthenings. The mean tibia shortening
      was 5.8 cm. We used the Ilizarov technique in all cases. The mean follow-up time
      was 7.2 years. The mean lengthening was 23% of the former length. The healing
      index was 50.8 days/cm. In the final examination six patients were skeletally
      mature, equal limb length and functional foot positioning were achieved in four
      of them. Complications were observed during 14 lengthenings (87.5%). Although
      lengthening in fibular hemimelia is difficult, elongation with axis and foot
      correction may offer an alternative to amputation.

PMID- 16436953
TI  - Articulated hip distraction or arthrodiatasis.

PMID- 16436954
TI  - Preemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus
      disease in solid organ transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and
      mortality in solid organ transplant recipients. Preemptive treatment with
      antiviral agents of patients with CMV viremia has been widely adopted as an
      alternative to routine prophylaxis to prevent CMV disease. This study was
      conducted to evaluate the efficacy of preemptive treatment in preventing
      symptomatic CMV disease. METHODS: The Cochrane CENTRAL Registry, MEDLINE, EMBASE,
      and reference lists were searched for randomized trials of preemptive treatment
      in solid organ transplant recipients. Two authors extracted all data; analysis
      was with a random effects model and results expressed as relative risk (RR) and
      95% confidence intervals (CI). RESULTS: Ten eligible trials (476 patients) were
      identified, six of preemptive treatment versus placebo or standard care
      (treatment of CMV when disease occurred), three of preemptive treatment versus
      antiviral prophylaxis and one of oral versus intravenous preemptive treatment.
      Compared with placebo or standard care, preemptive treatment significantly
      reduced the risk of CMV disease (6 trials, 288 patients, RR 0.29, 95% CI 0.11 to
      0.80) but not acute rejection (3 trials, 185 patients, RR 1.06, 95% CI 0.64 to
      1.76) or all-cause mortality (2 trials, 176 patients, RR 1.23, 95% CI 0.35 to
      4.30). Comparative trials of preemptive therapy versus prophylaxis showed no
      significant difference in the risks of CMV disease (2 trials, 151 patients, RR
      0.42, 95% CI 0.07 to 2.65), acute rejection (1 trial, 70 patients, RR 0.94, 95%
      CI 0.42 to 2.09) or all-cause mortality (3 trials, 151 patients, RR 1.86, 95% CI
      0.61 to 5.72). CONCLUSIONS: Few randomized trials have evaluated the effects of
      preemptive therapy to prevent CMV disease. Preemptive therapy is effective
      compared with placebo or standard care, but additional head-to-head trials are
      required to determine the relative benefits and harms of preemptive therapy and
      prophylaxis to prevent CMV disease in solid organ transplant recipients.

PMID- 16436955
TI  - A critical role for granzyme B, in addition to perforin and TNFalpha, in
      alloreactive CTL-induced mouse pancreatic beta cell death.
AB  - BACKGROUND: The precise effector mechanisms and molecular mediators used by
      alloreactive cytotoxic T lymphocytes to kill transplanted pancreatic beta cells
      are poorly defined. We have used mouse (H2b-anti-d) CTLs raised in strains
      deficient in various key cytotoxic effector molecules to assess the importance of
      the various signaling pathways mobilized to kill primary mouse pancreatic islet
      cells, the beta cell line NIT-1, and NIT-1 cells overexpressing dominant-negative
      FADD and Bcl-2. METHODS: Death of target cells was assessed using 51Cr release
      assays. RESULTS: In short-term assays (<5 hours) beta cell death did not require
      a functional FasL/Fas pathway, and was not inhibited by Bcl-2. However, the
      absence of either perforin or granzyme B resulted in cell survival. By contrast,
      a crucial role for granzyme B was not seen when hematopoietic P815 cells were
      used as targets, indicating differential regulation of apoptosis. Interestingly,
      coincubation with CTL for 24 hours revealed an additional but less potent "late
      phase" of beta cell death that did not require perforin. This delayed death was
      blocked by dominant-negative FADD, but not by Bcl-2, and was likely to be due to
      TNFalpha secretion. CONCLUSIONS: This study suggests that strategies to protect
      beta cells from allogeneic CTL attack will need to inhibit the perforin/granzyme
      and probably also the TNFalpha pathway. As there are no known pharmacological
      approaches to blocking perforin, therapeutic approaches based on overexpressing
      both dominant negative FADD and an inhibitor of granzyme B may hold promise in
      prolonging beta cell survival in the allogeneic setting.

PMID- 16436956
TI  - Utility of a mathematical nomogram to predict delayed graft function: a single
      center experience.
AB  - BACKGROUND: In 2003, Irish and colleagues published a weighted nomogram designed
      to predict the risk of delayed graft function (DGF) in a given transplant. It was
      anticipated that the predictive nomogram would permit preemptive therapies or
      allocation decisions based on the risk of DGF. The potential for reducing
      unfavorable outcomes and expenses appeared significant. This nomogram, however,
      was developed using population data found in the United States Renal Data System
      and has not been prospectively validated. METHODS: We evaluated the accuracy and
      utility of this nomogram in all cadaver renal transplants performed at a single
      transplant center. In addition, we correlated DGF with a variety of independent
      donor and recipient variables outside the established nomogram. RESULTS: The
      average nomogram DGF risk was 0.41 (a 41% chance of DGF) among the 169 cases in
      our population. The mean was 0.45+/-0.14 (confidence interval: 0.40-0.49) for the
      42 DGF-positive subjects, and 0.40+/-0.14 (confidence interval: 0.38-0.43) for
      the 127 DGF-negatives (t=1.80; P=0.07). CONCLUSIONS: Although there was a trend
      showing the predictive value of the nomogram the overlap was tremendous, limiting
      the accuracy of the calculation for any single recipient. Prospective application
      of a nomogram on a case-by-case basis did not contribute meaningful information
      that could guide clinical decision-making regarding use, allocation or
      immunosuppressive regimen aimed at minimizing DGF.

PMID- 16436957
TI  - Renal transplantation reverses functional deficiencies in circulating dendritic
      cell subsets in chronic renal failure patients.
AB  - BACKGROUND: Dendritic cell (DC) subsets play critical roles in regulation of
      innate and adaptive immune responses. These important antigen-presenting cells
      have not been extensively analyzed in chronic renal failure (CRF), during
      dialysis, or before and after renal transplantation. METHODS: The incidence of
      circulating precursor (pre)-DC subsets relative to total peripheral blood
      mononuclear cells was analyzed in healthy controls, haemodialysis patients,
      peritoneal dialysis patients, CRF patients, and renal transplant (RT) recipients.
      DC subsets were identified and characterized phenotypically by multicolour flow
      cytometric analysis and purified by immunomagnetic bead isolation respectively.
      Cytokine production and circulating DC mobilizing cytokines were determined by
      ELISA. RESULTS: The incidence of circulating prePDC was reduced in all patients,
      but the incidence of circulating preMDC was comparable in RT and dialysis
      patients compared to healthy controls. CRF patients exhibited the lowest
      incidence of circulating preMDC and prePDC. Immunomagnetic bead-isolated preMDC
      and prePDC from haemodialysis patients were functionally impaired (reduced
      expression of surface costimulatory molecules and interleukin-12p70 production
      following bacterial lipopolysaccharide stimulation, and reduced interferon-alpha
      production following herpes simplex virus stimulation respectively, compared to
      healthy controls and RT recipients. Glomerular filtration rate correlated
      significantly with the incidence of circulating preMDC, but not prePDC.
      CONCLUSIONS: Deficiencies in the incidence and function of precursor DC can be
      reversed with successful renal transplantation achieving normal renal function.
      However, the finding of reduced incidence of circulating prePDC in the peripheral
      blood in RT recipients may be of significance in the pathogenesis of infections
      and malignancies.

PMID- 16436958
TI  - Ischemic preconditioning of cadaver donor livers protects allografts following
      transplantation.
AB  - BACKGROUND: Ischemic preconditioning (IP) has been shown in animal models to
      protect livers against ischemia/reperfusion injury. The aim of this clinical
      study is to investigate whether IP of cadaver livers prior to retrieval confers
      protection on the allografts. METHODS: Cadaveric donor livers were subjected to
      IP prior to retrieval by clamping of the hepatic pedicle for 10 min followed by
      reperfusion. Biopsies were obtained from the preconditioned (n=9) and control
      nonpreconditioned (n=14) liver transplants prior to and 2 hr following
      reperfusion. Cryosections were stained with antibodies against neutrophils and
      platelets. RESULTS: IP livers were associated with significantly lower serum
      levels of aspartate aminotransferase (240+/-98 IU/L vs. 382+/-163 IU/L; P>0.016)
      and lactate (0.81+/-0.07 mmol/L vs. 1.58+/-0.9 mmol/L; P>0.018) 24 hr following
      transplantation. Furthermore, recipients of IP livers spent a significantly
      shorter time in the intensive care unit following transplantation compared to
      those given nonpreconditioned allografts (1 vs. 2.8+/-1.6 days; P=0.0008).
      Increases in neutrophil infiltration were detected in 6/14 (43%; P=0.022) and in
      CD41 deposition in 5/14 (36%; P=0.042) of nonpreconditioned livers. However, none
      of the IP allografts showed any change in the levels of platelets or neutrophil
      infiltration following transplantation. CONCLUSION: IP is an effective method of
      protecting cadaver donor allografts from cold ischemia and subsequent reperfusion
      injury. IP is also associated with a reduction in the nonspecific inflammatory
      response.

PMID- 16436959
TI  - Risk of lymphoma after renal transplantation varies with time: an analysis of the
      United States Renal Data System.
AB  - BACKGROUND: Characterization of the incidence of posttransplant lymphoma over
      time may help guide the timing and intensity of posttransplant monitoring. We
      analyzed the United States Renal Data System to describe the occurrence of
      lymphoma following renal transplantation. METHODS: All end-stage renal disease
      patients placed on the transplant waiting list between January 1, 1990 and
      December 31, 1999 were considered. Survival analysis was used to estimate
      lymphoma risk in renal transplant patients. RESULTS: Of 89,260 eligible patients,
      a total of 556 lymphoma cases were identified with 357 in transplant patients.
      The overall rate of posttransplant lymphoma was 33.3/10,000 person-years in
      transplant patients. There was variation in the duration and magnitude of
      increased lymphoma risk by age. The highest rates of lymphoma were among
      transplanted patients in the first 12 months, after which the rate of lymphoma
      decreased. Among Caucasian transplant recipients less than 25 years of age, the
      adjusted relative risk of lymphoma ranged from 13.82 [95% CI: (3.96, 48.15)]
      within 6 months posttransplant to 3.46 [95% CI: (0.69, 17.44)] within months 30
      36 posttransplant. Only patients under 25 years had a notably increased risk
      beyond the first 2 posttransplant years. The risk of lymphoma differed by race,
      with Caucasian patients at nearly double the risk of African-Americans. Gender
      was not associated with lymphoma incidence. CONCLUSIONS: We found and quantified
      a time-varying relationship between renal transplant and lymphoma risk. This
      information can be used in combination with knowledge of established risk factors
      to guide the schedule of posttransplant monitoring.

PMID- 16436960
TI  - Respiratory complications: a major concern after right hepatectomy in living
      liver donors.
AB  - BACKGROUND: One of the main concerns after living donor liver transplantation is
      the risk of morbidity and/or mortality that it imposes on the donors. Respiratory
      postoperative complications in living liver donors have already been reported but
      their frequency seems to be underestimated. We designed a prospective study to
      evaluate the rate and the nature of postoperative pulmonary complications in 112
      consecutive donors. METHODS: The medical records of the 112 living liver donors
      operated on at our center from 1998 to 2003 were reviewed and all the cases of
      respiratory complications were retrieved. Moreover, since 2000, all patients had
      a computed tomography angiography of the thorax at day 7 on a prospective basis.
      RESULTS: In all, 112 hepatectomies (44 right and 68 left) for adult-to-adult or
      adult-to-child liver donation were performed in our center. No postoperative
      mortality was recorded. Fourteen major respiratory complications developed in of
      11 of 112 donors (9.8%), in all cases after right hepatectomy, and included
      nonsevere pulmonary embolism (n=7), right pleural empyema (n=3), and bacterial
      pneumonia (n=3). Minor respiratory complications (7.1% of the donors) included
      iatrogenic pneumothorax (n=3) and pleural effusion requiring thoracocentesis
      (n=5). Abdominal complications (mainly biliary leak) developed in 10 donors
      (8.9%), who in the vast majority remained free of pulmonary complications.
      CONCLUSIONS: In our series, pulmonary complications are frequent in living liver
      donors. These complications are mainly observed after right hepatectomy. The
      particular prevalence of pulmonary embolism should lead to focus on its early
      diagnosis and prevention.

PMID- 16436961
TI  - Emergence of multiple cytomegalovirus strains in blood and lung of lung
      transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a major pathogen in lung transplant
      recipients (LTRs). The emergence of different CMV strains in lung and blood after
      transplantation has not yet been analyzed. METHODS: In total, 75 serum and 91
      broncheoalveolar lavage (BAL) samples obtained from 25 LTRs in the follow-up
      after transplantation were tested for the presence of different CMV strains. The
      gB, gN, and gO genes of the CMV isolates were analyzed by subtype-specific PCR,
      restriction fragment length polymorphism (RFLP), sequencing, and phylogenetic
      analysis. RESULTS: Mixed CMV-strain populations were detected after cessation of
      antiviral prophylaxis in up to 80% and 90% of the patients' BAL and serum,
      respectively, and this was independent of the CMV serostatus of donor and
      recipient. In five patients, the same single CMV strain was consistently
      detectable over at least 1 year in lung and blood, although in two of these cases
      donor and recipient had both been CMV-seropositive. Most CMV strains were
      distributed in the lung and blood compartment. Symptomatic CMV infection within
      the first year after transplantation was observed only in patients with mixed CMV
      strain populations (P<0.05). CONCLUSION: Most LTRs harbor more than one CMV
      strain in their lung and blood compartment after cessation of prophylaxis, but
      the CMV strain distribution within and between the compartments varies between
      individuals and is not associated with the donor/recipient serostatus. The data
      further show that compartmentalization of CMV strains in lung versus blood seems
      to be a rare event and that the presence of mixed CMV-strain infections within
      the first year after transplantation may be disadvantageous for LTRs.

PMID- 16436962
TI  - Risk stratification of adult patients undergoing orthotopic liver transplantation
      for fulminant hepatic failure.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is an effective treatment for
      fulminant hepatic failure (FHF), but postOLT mortality is higher for patients
      with FHF than for patients with other indications for OLT. In the current study,
      a large cohort of patients who underwent OLT for FHF was evaluated to develop and
      validate a system useful for estimating postOLT patient survival. METHODS: The
      1,457 patients who underwent OLT for FHF in the United States between 1988 and
      2003 were enrolled through the UNOS database. This group was divided into a
      modeling group (n=972) and a crossvalidation group (n=486). With a multivariate
      regression analysis, the modeling group was used to identify clinical parameters
      that had a significant association with postOLT survival. This regression
      analysis was used to create a scoring system that was subsequently assessed in
      the crossvalidation group. RESULTS: Four risk factors were identified with the
      multivariate analysis: 1) body mass index > or = 30 kg/m2; 2) serum creatinine >
      2.0 mg/dL; 3) recipient age > 50 years old; and 4) history of life support. By
      assigning points based on the number of risk factors present, the scoring system
      was able to differentiate between low-risk patients (5-year survival, 81%) and
      high-risk patients (5-year survival, 42%). The relative risk of postOLT mortality
      increased by approximately 150% for each additional point. CONCLUSION: The
      scoring system risk-stratified the crossvalidation group and accurately predicted
      postOLT survival. A scoring system utilizing clinical and demographic information
      readily available prior to OLT may help predict the probability of survival after
      OLT for FHF.

PMID- 16436963
TI  - Estimated one-year glomerular filtration rate is the best predictor of long-term
      graft function following renal transplant.
AB  - BACKGROUND: Long-term success of renal transplantation depends upon the quality
      of the donor organ, avoidance of peritransplant and early posttransplant damage
      (rejection), and optimal maintenance of graft function after the first 6-12
      months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate
      short-term success, whereas calculated GFR at 5 years gives a better appreciation
      of long-term outcomes. The objective of this study was to assess the effect of
      various demographic and transplant-related parameters on renal function via GFR
      at 1 year and 5 years post transplantation, using univariate and multivariate
      data analysis. METHODS: Data on 1-year GFR were available from 10,397 patients,
      whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients
      were enrolled in the Neoral Multinational Observational Study in Transplantation
      (Neoral-MOST), an ongoing, prospective, observational study of adult renal
      transplant recipients. RESULTS: One-year GFR was the most relevant predictor for
      5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a
      continuous variable, the effects of several highly relevant parameters from
      univariate analysis (such as acute rejection and delayed graft function) on 5
      year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas
      immunological risk factors like HLA match or previous transplantation had an
      ongoing effect on graft function beyond year 1. CONCLUSIONS: The findings of this
      study corroborate and augment data from previous registry surveys, and confirm
      the importance of observational studies in investigating the role of
      peritransplant parameters on long-term graft outcome.

PMID- 16436964
TI  - Dietary phytosterols reduce cyclosporine-induced hypercholesterolemia in
      apolipoprotein E-knockout mice.
AB  - BACKGROUND: Cyclosporine-induced hypercholesterolemia is a major concern after
      solid organ transplantation. Reducing this side effect of cyclosporine by dietary
      agents may be safe, cost-effective, and attractive to both patients and health
      professionals. METHODS: In this study, the interactions between dietary
      phytosterols (2% w/w) and cyclosporine (0.02% w/w) in regard to blood
      cyclosporine concentrations, lipoprotein profile, and histological and
      morphometrical features of atherosclerotic lesions were studied over 14 weeks in
      apolipoprotein E-knockout mice. RESULTS: Cyclosporine alone increased plasma non
      HDL cholesterol, and triglyceride concentrations and reduced HDL-cholesterol
      levels as compared to controls. However, these changes were not associated with
      further increases in atherogenesis as compared to controls. Unlike cyclosporine,
      phytosterols reduced non-HDL cholesterol and atherosclerosis, and increased HDL
      cholesterol concentrations, as compared to the control group. The addition of
      dietary phytosterols to cyclosporine reduced the extent of cyclosporine-induced
      hypercholesterolemia, but not cyclosporine-induced hypertriglyceridemia. The
      extent of atherosclerosis in the combination therapy group was significantly
      lower than that in the control group or cyclosporine-treated group. Blood
      cyclosporine concentrations were comparable between the two groups of
      cyclosporine-treated and the combination therapy groups at the end of the study.
      CONCLUSION: This study suggests that simultaneous consumption of dietary
      phytosterols and cyclosporine may attenuate posttransplant hypercholesterolemia
      associated with the immunosuppressive cyclosporine. Additional studies are
      required to understand the mechanisms by which dietary phytosterols reduce
      cyclosporine-induced hypercholesterolemia.

PMID- 16436965
TI  - Graft loss from recurrent glomerulonephritis is not increased with a rapid
      steroid discontinuation protocol.
AB  - BACKGROUND: The risk of recurrence of glomerulonephritis in kidney transplant
      recipients on a steroid-free maintenance immunosuppression protocol is unknown.
      METHODS: We studied the 4-year graft and patient survival in 105 adult kidney
      transplant recipients who received their transplant for glomerulonephritis (GN)
      and were treated with a protocol incorporating rapid discontinuation of
      prednisone for 5 days (group 1). We compared these outcomes to two control
      groups; 439 concurrent recipients who received a transplant for causes other than
      GN (group 2) and to 260 kidney transplant recipients who received an allograft
      for GN between 1994 and 1999 and were maintained on a steroid-based
      immunosuppressive protocol (group 3). RESULTS: The 4-year graft and patient
      survival were similar in the three groups. Acute rejection-free survival was also
      similar. Serial annual serum creatinine and estimated GFR were also comparable
      amongst the three groups. Two grafts were lost in group 1 from biopsy-proven
      recurrent GN and eight other subjects had evidence of histological recurrence at
      11.2+/-11.9 months. Seven grafts were lost for recurrent disease in group 3 and
      15 others had evidence of histological recurrence at 29.1+/-32.6 months. The mean
      time to graft loss from recurrence was 52+/-22 months. CONCLUSION: A regimen that
      utilizes rapid discontinuation of steroids conveys no added risk of graft loss
      from recurrent GN in the short term but longer follow-up is needed. A
      consideration should be made to discontinue corticosteroids in the potential
      recipients who are on them at the time of transplantation.

PMID- 16436966
TI  - Heart allograft protection with low-dose carbon monoxide inhalation: effects on
      inflammatory mediators and alloreactive T-cell responses.
AB  - BACKGROUND: Carbon monoxide (CO), a byproduct of heme catalysis, has lately
      received considerable attention as a regulatory molecule in cellular and
      biological processes. CO has been shown to provide potent protection against a
      variety of tissue injuries. We hypothesized in this study that low concentration
      CO would be beneficial for organ allografts, which frequently undergo several
      types of injury such as ischemia/reperfusion, alloimmune reaction, and
      inflammation METHODS: The efficacy of low-dose CO was examined in a fully
      allogeneic LEW to BN rat heterotopic heart transplantation (HHTx) model.
      Recipients were kept in air or exposed to low-dose CO (20 ppm) for 14, 28, or 100
      days after HHTx under short-course tacrolimus RESULTS: CO treatment (d0-28, 0
      100) was remarkably effective in prolonging heart allograft survival to a median
      of >100 from 45 days in the air-control group, with significant reductions of
      arteritis, fibrosis, and cellular infiltration, including macrophages and T
      cells. CO inhibited intragraft upregulation of Th1 type cytokines (IL-2,
      IFNgamma), proinflammatory mediators (IL-1beta, TNFalpha, IL-6, COX-2), and
      adhesion molecule. Shorter CO exposure in early (0-13d) and late (14-28d)
      posttransplant periods also prolonged graft survival, with a significant
      inhibition of inflammatory mediators CONCLUSIONS: These results show that low
      dose CO inhalation protects heart allografts and can considerably prolong their
      survival. CO appears to function via multiple mechanisms, including direct
      inhibition of Th1 type cytokine production and regulation of inflammatory
      responses.

PMID- 16436967
TI  - Improved cold preservation of kidney tubular cells by means of adding
      bioflavonoids to organ preservation solutions.
AB  - BACKGROUND: Cold ischemia and reperfusion during renal transplantation result in
      release of reactive oxygen species. The aim of this study is to examine whether
      cold storage induced cell injury can be ameliorated by adding flavonoids directly
      to preservation solutions. METHODS: Cultured renal tubular epithelial cells (LLC
      PK1) were stored in University of Wisconsin (UW) or Euro-Collins (EC) solution at
      4 degrees C for 20 hours. Preservation solutions were supplemented with various
      flavonoids. After rewarming, structural and metabolic cell integrity was measured
      by lactate dehydrogenase (LDH) release and MTT-test, and lipid peroxidation was
      assessed from generation of thiobarbituric acid-reactive substances (TBARS).
      RESULTS: Twenty hours of cold storage resulted in a substantial loss of cell
      viability in both preservation solutions (in EC: LDH release 92.4+/-2.7%; MTT
      test 0.5+/-0.7%). Addition of luteolin, quercetin, kempferol, fisetin, myricetin,
      morin, catechin, and silibinin significantly reduced cell injury (for luteolin in
      EC: LDH release 2.4+/-1.6%; MTT-test 110.3+/-10.4%, P<0.01; TBARS-production
      (related to cold stored control cells) 8.9+/-2.6%). No cytoprotection was found
      for apigenin, naringenin, and rutin. Protective potency of flavonoids depends on
      number of hydroxyl-substituents and lipophilicity of the diphenylpyran compounds.
      CONCLUSION: Cold storage induced injury of renal tubular cells was substantially
      ameliorated by adding selected flavonoids directly to preservation solutions.

PMID- 16436968
TI  - Lentiviral gene transfer of the chemokine antagonist RANTES 9-68 prolongs heart
      graft survival.
AB  - BACKGROUND: Allograft tolerance might be achieved by expressing immunomodulatory
      proteins through gene therapy. We have evaluated the possibility of promoting
      significantly allograft survival in a vascularized cardiac allograft model by
      performing ex vivo gene transfer. We used a lentiviral vector encoding the
      chemokine antagonist RANTES 9-68 that is capable of competing with native RANTES.
      METHODS: The Fisher donor/Lewis recipient rat strain combinations were used and
      all animals received for the first 5 days posttransplantation a subtherapeutic
      dose of cyclosporine A (1.5 mg/kg). Ex vivo gene transfer into heart allograft
      was performed by multiple injections of the SIN.cPPT lentiviral vector, which
      corresponds to the multiply attenuated, self-inactivating lentivector derived
      from the human immunodeficiency virus (HIV)-1. RESULTS: About 6% of the cardiac
      tissue had integrated lentiviral vector, which closely matches the mean in vivo
      RANTES antagonist expression of 5% obtained by immunohistochemistry. In vivo
      RANTES 9-68 expression has significantly prolonged graft survival (median [25%
      75%]: 20 [17-26] days), compared to the control 15 ([14-15] days; P=0.0007).
      Furthermore, hearts transduced with RANTES 9-68 showed a significant (P<0.05)
      reduction in cell infiltration and intragraft expression of TNF-alpha, IFN-gamma,
      endogenous RANTES, and TGF-beta. CONCLUSION: Lentiviral gene transfer of RANTES 9
      68 antagonist attenuates significantly the inflammatory response and delays
      allograft rejection, despite low levels of transduction. Future improvement of
      heart transduction by lentiviral vectors, as it has been achieved with other
      vectors, might become an attractive alternative therapy for treating allografts
      that require sustained gene expression for better organ preservation.

PMID- 16436969
TI  - Mutations in innate immune system NOD2/CARD 15 and TLR-4 (Thr399Ile) genes
      influence the risk for severe acute graft-versus-host disease in patients who
      underwent an allogeneic transplantation.
AB  - BACKGROUND: NOD2 and TLR-4 genes belong to the innate immune system that detects
      invading pathogens through several pattern-recognition receptors. Here we
      analyzed 403 patients for NOD2 gene mutations and 307 patients for TLR-4 gene
      mutations (Thr399Ile) with their respective donors and correlated the results
      with the incidence of acute graft-versus-host disease (aGVHD), severe acute GVHD
      (saGVHD), the risk for transplant-related mortality (TRM), overall survival (OS)
      and incidence of infectious complications. METHODS: We performed a retrospective
      single-center study. Genotyping of TLR-4 and NOD2 were evaluated by real-time
      polymerase chain reaction. RESULTS: Surprisingly, we found a significant reduced
      incidence of aGVHD, saGVHD, and intestinal GVHD for patients with NOD2 gene
      mutations on the donor side with 50%, 0% and 2% compared to patients with the
      wild-type NOD2 gene with 65%, 17%, and 26%, respectively (P<0.02). However, the
      incidence of saGVHD increased in patients with NOD2 mutations on the patient and
      donor (P/D) side with 44% versus 17% compared to patients with the wild-type gene
      (P<0.03). TLR-4 gene mutations at P/D side had an increased risk for saGVHD with
      42% versus 15% of patients with wild-type gene (P<0.04). OS, TRM, and incidence
      of infectious complications were not influenced by the mutated genes.
      Multivariate analysis confirmed that NOD2 gene mutations on the donor side had a
      reduced risk for saGVHD (P<0.001), whereas mutations of the NOD2 gene on P/D side
      had an increased risk for saGVHD (P<0.01) in our analysis. CONCLUSIONS: These
      results suggest that NOD2 mutations have influence on the occurrence of acute
      GVHD after transplantation.

PMID- 16436970
TI  - Alloimmunity in primate heart recipients with CD154 blockade: evidence for
      alternative costimulation mechanisms.
AB  - BACKGROUND: CD154 mediates key facets of humoral and cellular immunity to
      alloantigens, and is tolerogenic to influenza antigens in primates. Barriers to
      CD154-based tolerance induction for primate cardiac allografts have not
      previously been defined. METHODS: Heterotopic cardiac allograft outcomes in
      cynomolgus monkeys treated with a CD154 inhibitor, IDEC-131 (n=27), were compared
      to no treatment (n=4) or cyclosporine A (n=6). RESULTS: CD154 blockade
      significantly prolonged median allograft survival, from 6.2 (range 6, 7, n=4)
      days in untreated controls, to 39 (8,112, n=16) days with intensive monotherapy
      and 93 (>25, 386; n=3) days with added antithymocyte globulin (ATG), but did not
      yield tolerance. Alloantibody production was delayed but not prevented by IDEC
      131 alone or with ATG, and was exacerbated by infusion of donor bone marrow
      (n=8). Expression of ICOS was prominent in graft infiltrating lymphocytes, and
      preceded elaboration of antidonor antibody and vasculopathy. CONCLUSION: CD154
      monotherapy modulates primate cardiac alloimmunity, but does not readily induce
      tolerance. Targeting alternative costimulation pathways, including ICOS, may
      facilitate tolerance induction based on CD154 blockade.

PMID- 16436971
TI  - Regulation of B- and T-cell mediated xenogeneic transplant rejection by
      interleukin 12.
AB  - BACKGROUND: Xenotransplantation may provide a solution to the increasing shortage
      of donor organs. Acute vascular rejection and cell-mediated rejection remain the
      primary barriers to successful xenotransplantation. In animal models where acute
      vascular rejection can be attenuated, xenografts succumb to cell-mediated
      rejection. The mechanisms of acute vascular rejection and cell-mediated rejection
      are poorly understood. METHODS: Using a heterotopic rat-to-mouse cardiac
      transplantation model, we demonstrate that IL-12p40 attenuates both allogeneic
      and xenogeneic acute vascular rejection pathology by suppressing B-cell
      activation and anti-rat isotype switching. To study the mechanism of xenogeneic
      cell-mediated rejection, we use B-cell deficient mice that only develop cell
      mediated rejection pathology. To elucidate the role of IL-12 in cell-mediated
      rejection, we generated B cell/ IL-12p40 double knockout mice. RESULTS: We
      demonstrate that xenogeneic cell-mediated rejection is mediated by CD4+ T cells,
      and is accompanied by elevated FasL and granzyme mRNA expression. Strikingly, by
      generating B cell/IL-12p40 double knockout mice, we demonstrate that xenogeneic
      cell-mediated rejection is IL-12p40 dependent. In contrast, we demonstrate that
      allogeneic cellular rejection is IL-12p40 independent. CONCLUSIONS: We conclude
      that IL-12 plays a dual role in xenotransplantation by driving xenogeneic CD4+ T
      cell responses but suppressing both allogeneic and xenogeneic B cell responses.
      Therefore, the mechanism of allogeneic and xenogeneic transplantation rejection
      is differentially regulated by IL-12.

PMID- 16436972
TI  - The role of anti-non-Gal antibodies in the development of acute humoral xenograft
      rejection of hDAF transgenic porcine kidneys in baboons receiving anti-Gal
      antibody neutralization therapy.
AB  - BACKGROUND: The present study was undertaken to determine the role of preformed
      and induced anti-non-Gal antibodies in the rejection of hDAF pig-to-baboon kidney
      xenotransplants after anti-Gal antibody neutralization therapy. METHODS: Seven
      baboons received life-supporting kidney transplants from hDAF transgenic pigs.
      Anti-Gal antibodies were neutralized by GAS914 or TPC (a Gal PEG glycoconjugate
      polymer). Group 1 (n=5) underwent a conventional immunosuppressive therapy with
      FK506, rabbit anti-thymocyte serum/immunoglobulin, mycophenolate mofetil, and
      steroids. Group 2 (n=2) received an anti-humoral immunity regimen with LF15-0195,
      Rituxan and cobra venom factor in addition to ATG, FK506 and steroids. Levels of
      anti-non-Gal antibodies and their mediated complement-dependent cytotoxic
      activities (CDC) were detected by flow cytometry using Gal knockout (k/o) pig
      lymphocytes (LC) or endothelial cells (EC) as targets. RESULTS: Continuous
      infusion of GAS914/TPC significantly reduced anti-Gal antibodies. In Group 1,
      four of five baboons developed severe acute humoral xenograft rejection (AHXR)
      and the rejection was associated with either a high level of preformed anti-non
      Gal IgG or a marked elevation in induced anti-non-Gal IgG and IgM. Sera collected
      at the time of AHXR had a high level of CDC to porcine LC/EC from Gal k/o
      animals. The intensive anti-humoral therapy in Group 2 completely inhibited both
      anti-Gal and non-Gal antibody production and prevented AHXR. However, this
      therapy was not well tolerated by the baboons. CONCLUSION: In a pig-to-baboon
      kidney transplant model, both preformed and induced anti-non-Gal antibodies are
      strongly associated with the pathogenesis of AHXR when anti-Gal antibodies are
      neutralized.

PMID- 16436973
TI  - Successful transplantation of cadaveric polycystic liver: case report and review
      of the literature.
AB  - The number of candidates awaiting liver transplantation continues to exceed the
      available donor organ pool. This steadily increasing donor organ shortage calls
      for the widening of selection criteria for potential donor organs. Strategies to
      increase the number of liver allografts include liver splitting, use of donors
      over 70 years, use of steatotic donor livers, and reutilization of liver
      allografts after brain death of the first recipient. We report the successful use
      of a polycystic donor liver and review the experience with this donor population.
      We propose that the selective use of polycystic donor livers containing small (<5
      cm) cysts with preserved liver parenchyma is safe and appropriate.

PMID- 16436974
TI  - Mycophenolate mofetil and bronchiectasis in kidney transplant patients: a
      possible relationship.
AB  - Bronchiectasis is a rare acquired condition, generally resulting from long-term
      chronic pulmonary inflammation. Mycophenolate mofetil (in short, mofetil) is a
      commonly used immunosuppressant in kidney transplantation. In the literature,
      there is no report of a relationship between mofetil use and development of
      bronchiectasis. Five kidney transplant patients developed complaints of cough,
      dyspnea, and abundant sputum production without apparent cause. Pulmonary
      complaints started at a range of 0-20 months after the start of mofetil
      treatment. Lesions were classified as bronchiectasis(-like), based on clinical
      presentation, chest x-ray, and computed tomography scan. Withdrawal of mofetil
      greatly relieved pulmonary complaints. Since the first kidney transplantation in
      our center in 1968, we have had no diagnosis of bronchiectasis in over 1,500
      patients without mofetil treatment. These cases suggest an association between
      mofetil and development of bronchiectasis. Converting mofetil to another
      immunosuppressive drug should be considered when unexplained pulmonary complaints
      develop in patients receiving mofetil.

PMID- 16436975
TI  - Screening for tuberculosis in the study of the living renal donor in a developing
      country.
AB  - Given the high prevalence of tuberculosis (Tb) in the Mexican population, a
      strict program to detect Tb in the potential donor is required. Chest x-ray,
      excretory urogram, urinalysis with microscopic exam of the sediment, urine
      cultures for M. tuberculosis, and tuberculin skin test (TST) with PPD-RT23
      performed for evaluation of 222 living donors were reviewed. Isoniazid
      prophylaxis before kidney donation was gathered. Donors and recipients were
      followed up for a minimum of 2 years. According to the TST result, 36.8% of the
      donors had latent tuberculosis; however, all other studies were normal or
      negative in all of them. Use of isoniazid prophylaxis in TST-positive donors made
      no difference in risk of transmission of tuberculosis to the recipient or
      development of tuberculosis among the donors. Normal chest x-ray and excretory
      urogram, along with a negative microscopic examination of the urine, safely
      exclude tuberculosis transmission to recipients.

PMID- 16436976
TI  - T-tube drainage for biliary stenosis after living donor liver transplantation.
AB  - The optimal strategies for bile duct stenosis after living donor liver
      transplantation with duct-to-duct biliary reconstruction remain unclear. Patients
      who underwent liver transplantation with duct-to-duct bile duct reconstruction
      (n=182) and were complicated with biliary stenosis (n=34) were analyzed.
      Treatment of biliary stenosis was attempted using an endoscopic approach or
      transhepatic biliary drainage. When this failed, the T-tube drainage technique
      was indicated. T-tube placement was performed in 14 patients. Intraoperative
      ultrasonography was performed to identify the bile duct. The common bile duct was
      cut open, a Kelly clamp was inserted and the stenotic portion was dilated, and a
      T-tube was inserted. The patients were scheduled to have the tube removed 1 year
      after insertion. Complications following T-tube placement or T-tube removal were
      negligible. The present technique can be an effective therapeutic option when
      endoscopic treatment is unsuccessful.

PMID- 16436977
TI  - A case of emphysematous pyelonephritis in a renal allograft.

PMID- 16436978
TI  - Plasmapheresis and RATG-induced serum sickness.

PMID- 16436979
TI  - Organ-specific differences in acute rejection intensity in a multivisceral
      transplant.

PMID- 16436980
TI  - Revision tympanoplasty using scar tissue graft.
AB  - OBJECTIVE: To evaluate the success rate of subcutaneous postsurgical scar tissue
      as graft material for revision tympanoplasty operations. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Thirty
      five patients who underwent revision tympanoplasty with or without mastoidectomy
      procedures and 36 patients undergoing primary operations who had all the data
      necessary for the study and a minimum follow-up of 6 months. The mean follow-up
      period was 12 months (range, 6-18 mo). Mean age, perforation size, cholesteatoma
      presence, time required for harvesting, and adjunctive mastoidectomies were
      similar between the two groups. INTERVENTION: The patients undergoing revision
      tympanoplasty had graft material harvested from the subcutaneous scar tissue. In
      the control group, temporalis fascia graft was used as graft tissue. MAIN OUTCOME
      MEASURES: The rate of perforation closure and postoperative hearing change was
      measured. RESULTS: In the scar tissue tympanoplasty group, 32 of 35 patients
      (91%) had successful closure of the tympanic membrane perforation, whereas in the
      control group, the success rate was 92% (p > 0.05). Mean postoperative pure-tone
      average improvement was 21 dB in the scar tissue tympanoplasty group and 18 dB in
      the control group (p > 0.05). CONCLUSION: Subcutaneous scar tissue is as
      successful in perforation closure and hearing improvement as temporalis fascia
      graft. The use of subcutaneous scar tissue graft is advantageous to other graft
      materials used in revision tympanoplasty operations in that it can be harvested
      through the same incision, does not add to the operative time, and does not carry
      the cost or risk of acellular dermis.

PMID- 16436981
TI  - Determinants of hearing loss in perforations of the tympanic membrane.
AB  - BACKGROUND: Although tympanic membrane perforations are common, there have been
      few systematic studies of the structural features determining the magnitude of
      the resulting conductive hearing loss. Our recent experimental and modeling
      studies predicted that the conductive hearing loss will increase with increasing
      perforation size, be independent of perforation location (contrary to popular
      otologic belief), and increase with decreasing size of the middle-ear and mastoid
      air space (an idea new to otology). OBJECTIVE: To test our predictions regarding
      determinants of conductive hearing loss in tympanic membrane perforations against
      clinical data gathered from patients. STUDY DESIGN: Prospective clinical study.
      SETTING: Tertiary referral center. INCLUSION CRITERIA: Patients with tympanic
      membrane perforations without other middle-ear disease. MAIN OUTCOME MEASURES:
      Size and location of perforation; air-bone gap at 250, 500, 1,000, 2,000, and
      4,000 Hz; and tympanometric estimate of volume of the middle-ear air spaces.
      RESULTS: Isolated tympanic membrane perforations in 62 ears from 56 patients met
      inclusion criteria. Air-bone gaps were largest at the lower frequencies and
      decreased as frequency increased. Air-bone gaps increased with perforation size
      at each frequency. Ears with small middle-ear volumes, < or = 4.3 ml (n = 23),
      had significantly larger air-bone gaps than ears with large middle-ear volumes, >
      4.3 ml (n = 39), except at 2,000 Hz. The mean air-bone gaps in ears with small
      volumes were 10 to 20 dB larger than in ears with large volumes. Perforations in
      anterior versus posterior quadrants showed no significant differences in air-bone
      gaps at any frequency, although anterior perforations had, on average, air-bone
      gaps that were smaller by 1 to 8 dB at lower frequencies. CONCLUSION: The
      conductive hearing loss resulting from a tympanic membrane perforation is
      frequency-dependent, with the largest losses occurring at the lowest sound
      frequencies; increases as size of the perforation increases; varies inversely
      with volume of the middle-ear and mastoid air space (losses are larger in ears
      with small volumes); and does not vary appreciably with location of the
      perforation. Effects of location, if any, are small.

PMID- 16436983
TI  - Cochlear implantation of patients with far-advanced otosclerosis.
AB  - OBJECTIVE: This current single-subject, repeated-measures study was to describe
      our experience with 30 patients who had been diagnosed with "far-advanced
      otosclerosis" and who were included in our program of cochlear implants. We
      analyzed the history of the patients and their families before implantation, the
      surgical findings, and the performance over a follow up of 3 years. MATERIAL AND
      METHODS: All patients met one or more of the after criteria: 1) previous surgical
      intervention as a treatment of their otosclerosis; 2) signs of pericochlear
      hypodensities in high resolution computed tomography (HRCT) scans; and 3) family
      precedents of otosclerosis. All underwent standard surgical cochlear
      implantation. RESULTS: In 78% of the cases, a stapedectomy had previously been
      realized. Cochlear otosclerosis could be appreciated in HRCT in 78% of the
      patients. A family history of otosclerosis was found in 40%, and 33.3% of
      patients had familial precedents of nonfilial hypoacusis. The mean results in the
      two-syllable test were 20% preimplantation, 54% 6 months after implantation, and
      52%, 62%, 54% at 1, 2, and 3 years after implantation. In the CID sentence test,
      they were in the order of 32% preimplantation and of 64% at 6 months, 66% after 1
      year, of 68% after 2 years, and reaching 72% after 3 years. No complications
      related to the surgery were detected. CONCLUSION: Patients diagnosed with far
      advanced otosclerosis have a good prognosis with cochlear implantation comparable
      to that of other patients in whom postlingual implants are performed.

PMID- 16436982
TI  - In vivo imaging of mammalian cochlear blood flow using fluorescence
      microendoscopy.
AB  - AIMS: We sought to develop techniques for visualizing cochlear blood flow in live
      mammalian subjects using fluorescence microendoscopy. BACKGROUND: Inner ear
      microcirculation appears to be intimately involved in cochlear function. Blood
      velocity measurements suggest that intense sounds can alter cochlear blood flow.
      Disruption of cochlear blood flow may be a significant cause of hearing
      impairment, including sudden sensorineural hearing loss. However, inability to
      image cochlear blood flow in a nondestructive manner has limited investigation of
      the role of inner ear microcirculation in hearing function. Present techniques
      for imaging cochlear microcirculation using intravital light microscopy involve
      extensive perturbations to cochlear structure, precluding application in human
      patients. The few previous endoscopy studies of the cochlea have suffered from
      optical resolution insufficient for visualizing cochlear microvasculature.
      Fluorescence microendoscopy is an emerging minimally invasive imaging modality
      that provides micron-scale resolution in tissues inaccessible to light
      microscopy. In this article, we describe the use of fluorescence microendoscopy
      in live guinea pigs to image capillary blood flow and movements of individual red
      blood cells within the basal turn of the cochlea. METHODS: We anesthetized eight
      adult guinea pigs and accessed the inner ear through the mastoid bulla. After
      intravenous injection of fluorescein dye, we made a limited cochleostomy and
      introduced a compound doublet gradient refractive index endoscope probe 1 mm in
      diameter into the inner ear. We then imaged cochlear blood flow within individual
      vessels in an epifluorescence configuration using one-photon fluorescence
      microendoscopy. RESULTS: We observed single red blood cells passing through
      individual capillaries in several cochlear structures, including the round window
      membrane, spiral ligament, osseous spiral lamina, and basilar membrane. Blood
      flow velocities within inner ear capillaries varied widely, with observed speeds
      reaching up to approximately 500 microm/s. CONCLUSION: Fluorescence
      microendoscopy permits visualization of cochlear microcirculation with micron
      scale optical resolution and determination of blood flow velocities through
      analysis of video sequences.

PMID- 16436984
TI  - Modiolar coiling, electrical thresholds, and speech perception after cochlear
      implantation using the nucleus contour advance electrode with the advance off
      stylet technique.
AB  - OBJECTIVE: Perimodiolar electrode arrays were developed in an attempt to improve
      stimulation of specific neural populations and to decrease electrical thresholds,
      thereby decreasing power consumption. Postoperative radiographs show that coiling
      of the arrays is variable. Our previous study explored the relationship between
      the angle of coiling, threshold levels, and functional outcomes using the Nucleus
      Contour electrode array. This study compares coiling angle, electrical threshold
      levels, and speech perception measures with the Nucleus Contour Advance electrode
      array implanted using the new advance off stylet technique versus the Nucleus
      Contour electrode array implanted using the standard technique. STUDY DESIGN:
      Retrospective review. SETTING: University medical center. PATIENTS: Forty-two
      adults and children with normal cochlear anatomy implanted with the Nucleus
      CI24RCA electrode using the advance off stylet technique with at least 1-year
      follow-up. INTERVENTION: Therapeutic. MAIN OUTCOME MEASURES: Computer-aided
      radiographic analysis of perimodiolar electrode placement, electrical threshold
      measurements, and speech perception outcome measures at 1 year postimplantation.
      RESULTS: The degree of modiolar coiling was tighter using the new electrode and
      technique in comparison with standard insertion technique using the Nucleus
      Contour electrode array. The tighter coiling tended to result in higher
      electrical thresholds. Lower speech perception outcome measures tended to
      correlate with a higher degree of coiling. CONCLUSION: The Nucleus Contour
      Advance electrode array combined with the advance off stylet technique resulted
      in a more consistent perimodiolar position. However, the tighter coiling resulted
      in statistically significant increased electrical thresholds and decreased speech
      perception outcomes. This finding may be secondary to multiple factors, not just
      coiling angle.

PMID- 16436985
TI  - Minimal access surgery for the Symphonix/Med-El Vibrant Soundbridge middle ear
      hearing implant.
AB  - OBJECTIVE: To develop a minimal access approach for implantation of the Vibrant
      Soundbridge middle ear hearing implant. This approach ideally uses the smallest
      skin incision possible, minimal or no hair shave, and the least possible amount
      of tissue and bone manipulation. This will facilitate the acceptability of the
      procedure to the general community and reduce the flap-related complication rate.
      The procedure is similar to the minimal access approach described for cochlear
      implantation. STUDY DESIGN: Eight patients with various degrees of sensorineural
      hearing loss and one with a mixed hearing loss who met implant criteria for the
      Vibrant Soundbridge middle ear hearing implant received the device over a 42
      month period. The first two patients underwent the traditional implant procedure
      with postauricular hair shave, postauricular S-shaped incision, and implant
      receiver suture fixation to the temporal bone. The following seven consecutive
      patients received a progressively smaller C-shaped postauricular skin incision,
      no hair shave, retrograde skull drilling for the implant seat, and no implant
      suture fixation until the technique closely approximated the minimal access
      cochlear implant procedure. Postoperative performance of the Soundbridge/Vibrant
      Med-El was evaluated through audiology testing and subjective patient reports.
      SETTING: Private neurotology clinic and tertiary care teaching hospital. RESULTS:
      The technique was feasible in all patients. Follow-up for the minimal access
      group ranged from 3 years to 5 months. There were no complications related to the
      approach, and all patients were satisfied users of the implant. The lack of hair
      shave and small incision size was greatly appreciated and warmly endorsed by the
      patients. CONCLUSION: The Vibrant Soundbridge/Vibrant Med-El can be safely
      implanted using the minimal access method that has been popularized for cochlear
      implant surgery. A large incision, extensive hair shave, risk of flap necrosis,
      and possibility of unsightly scar may deter patients from pursuing the potential
      benefits of implanted hearing technology. The technique may make the device more
      accessible to individuals who have concerns regarding cosmetics and potential
      flap complications.

PMID- 16436986
TI  - Amplification in the rehabilitation of unilateral deafness: speech in noise and
      directional hearing effects with bone-anchored hearing and contralateral routing
      of signal amplification.
AB  - OBJECTIVE: Vibromechanical stimulation with a semi-implantable bone conductor
      (Entific BAHA device) overcomes some of the head-shadow effects in unilateral
      deafness. What specific rehabilitative benefits are observed when the functional
      ear exhibits normal hearing versus moderate sensorineural hearing loss (SNHL)?
      DESIGN: The authors conducted a prospective trial of subjects with unilateral
      deafness in a tertiary care center. PATIENTS: This study comprised adults with
      unilateral deafness (pure-tone average [PTA] > 90 dB; Sp.D. < 20%) and either
      normal monaural hearing (n = 18) or moderate SNHL (PTA = 25-50 dB: Sp.D. > 75%)
      in the contralateral functional ear (n = 5). INTERVENTIONS: Subjects were fit
      with contralateral routing of signal (CROS) devices for 1 month and tested before
      (mastoid) implantation, fitting, and testing with a bone-anchored hearing aid
      (BAHA). OUTCOME MEASURES: Outcome measures were: 1) subjective benefit; 2) source
      localization tests (Source Azimuth Identification in Noise Test [SAINT]); 3)
      speech discrimination in quiet and in noise assessed with Hearing In Noise Test
      (HINT) protocols. RESULTS: There was consistent satisfaction with BAHA
      amplification and poor acceptance of CROS amplification. General directional
      hearing decreased with CROS use and was unchanged by BAHA and directional
      microphone aids. Relative to baseline and CROS, BAHA produced significantly
      better speech recognition in noise. Twenty-two of 23 subjects followed up in this
      study continue to use their BAHA device over an average follow-up period of 30.24
      months (range, 51-12 months). CONCLUSION: BAHA amplification on the side of a
      deaf ear yields greater benefit in subjects with monaural hearing than does CROS
      amplification. Advantages likely related to averting the interference of speech
      signals delivered to the better ear, as occurs with conventional CROS
      amplification, while alleviating the negative head-shadow effects of unilateral
      deafness. The advantages of head-shadow reduction in enhancing speech recognition
      with noise in the hearing ear outweigh disadvantages inherent in head-shadow
      reduction that can occur by introducing noise from the deaf side. The level of
      hearing impairment correlates with incremental benefit provided by the BAHA.
      Patients with a moderate SNHL in the functioning ear perceived greater increments
      in benefit, especially in background noise, and demonstrated greater improvements
      in speech understanding with BAHA amplification.

PMID- 16436987
TI  - Long-term assessment after implantation of the Vibrant Soundbridge device.
AB  - OBJECTIVE: To present long-term results with a semi-implantable middle ear
      implant, the Vibrant Soundbridge (VSB), and analyze pre- and post-operative
      results of audiologic tests. STUDY DESIGN: Retrospective chart review with
      additional patient interview and audiologic testing. SETTING: One tertiary
      referral center. SUBJECTS: Twenty patients who met the selection criteria of the
      manufacturer were evaluated at least two years after implantation. INTERVENTIONS:
      Monaural Implantation of the VSB in 20 patients, in two of these 20 patients
      implantation of the second ear in a second stage. RESULTS: Assessment of benefit
      and satisfaction using the standardized International Outcome Inventory for
      Hearing Aids, the Glasgow Benefit Inventory, and Visual Analogue Scales in all
      patients. Fifteen patients agreed to undergo audiologic testing at follow-up
      including pure-tone- and speech audiometry in silence and noise. The majority of
      patients (13/20) reported to be satisfied or very satisfied with the VSB. Aided
      speech perception was comparable between the VSB and the hearing aid
      preoperatively. When compared to the preoperative audiograms, residual hearing
      from 0.5-4 kHz was significantly worse in the operated ear with 8 dB (Wilcoxon
      signed rank test p < 0.001) but only 2.6 dB in the non-operated ear (Wilcoxon
      signed rank test, p > 0.05). Major surgical complications did not occur.
      Permanent alteration in taste occurred in three patients and revision surgery was
      necessary in another three patients. CONCLUSION: Satisfaction with the VSB was
      not superior to conventional hearing aids in subjective and in audiometric terms.
      Because of its impact on residual hearing and the requirement of implantation
      middle ear surgery, implantation of the VSB should be limited to patients with
      relevant side effects of hearing aids, e.g., severe chronic otitis externa.

PMID- 16436988
TI  - Diagnosis and management of salivary fistula after surgery for congenital aural
      atresia.
AB  - OBJECTIVE: Salivary fistula is an uncommon and unreported yet meaningful
      complication associated with the repair of congenital aural atresia. The capsule
      of the parotid gland may be violated during two steps of the operation: the
      initial dissection around the glenoid fossa or while aligning the auricle with
      the bony canal at the end of the procedure. We present the first described series
      of patients with salivary fistula after repair of congenital aural atresia. STUDY
      DESIGN: Retrospective case review from 1985 to 2004. SETTING: Tertiary referral
      center. PATIENTS: We included all patients who were diagnosed with a salivary
      fistula after congenital aural atresia repair. MAIN OUTCOME MEASURE: The
      diagnosis of a salivary fistula or salivary tissue in the external auditory canal
      after atresia repair was based on one of the following criteria: 1)
      identification of a fistula tract or salivary tissue in the external auditory
      canal, 2) otorrhea positive for amylase, or 3) intermittent otorrhea associated
      with eating. RESULTS: Of 1,500 patients operated on for aural atresia, we
      identified 6 with salivary fistula after atresia repair. Salivary fistulas were
      diagnosed from 15 days to 10 years postoperatively, and the duration ranged from
      6 months to 14 years. Treatment included observation, medical management, and
      surgical intervention. CONCLUSION: Salivary fistulas in the external auditory
      canal may present with granulation tissue, persistent crusting, or persistent
      otorrhea; it is therefore necessary to consider salivary fistula when managing
      these findings in postoperative congenital aural atresia patients. Salivary
      fistula secondary to repair of congenital aural atresia may be managed
      conservatively or surgically.

PMID- 16436989
TI  - The influence of unilateral versus bilateral clicks on the vestibular-evoked
      myogenic potentials.
AB  - OBJECTIVE: Because a continuous muscular effort is required during recording of
      vestibular-evoked myogenic potentials, we assume vestibular-evoked myogenic
      potentials elicited by simultaneous bilateral clicks can be used as a more
      convenient mode compared with respective unilateral clicks. To investigate
      whether bilateral clicks provide the same information as unilateral clicks, we
      examined whether the responses are different between them in normal subjects and
      whether bilateral clicks have the same diagnostic value as vestibular-evoked
      myogenic potentials elicited by unilateral clicks in detecting retrolabyrinthine
      lesions. STUDY DESIGN: Prospective study. SETTING: Academic tertiary referral
      center. SUBJECTS: Fourteen healthy volunteers and four patients with unilateral
      cerebellopontine angle tumors were enrolled in this study. INTERVENTIONS:
      Recordings of vestibular-evoked myogenic potential responses. MAIN OUTCOME
      MEASURES: The latency of each peak (p13, n23), the peak-to-peak interval, and
      amplitude (p13-n23). RESULTS: Both unilateral and bilateral click stimulation of
      28 ears (100%) produced vestibular-evoked myogenic potentials in normal subjects.
      The mean latencies of p13 and n23, peak-to-peak interval, and amplitude of
      vestibular-evoked myogenic potentials elicited with unilateral clicks were 11.62
      +/- 0.99 ms, 19.74 +/- 1.30 ms, 8.12 +/- 1.66 ms, and 110.79 +/- 61.37 microV,
      respectively, whereas those elicited with bilateral clicks were 11.16 +/- 0.51
      ms, 19.22 +/- 1.61 ms, 8.06 +/- 1.66 ms, and 111.77 +/- 40.98 microV,
      respectively. There was a significant difference (p < 0.05) in the latencies, but
      not for the interval and amplitude (p > 0.05). Four patients with unilateral
      cerebellopontine angle tumors and prolonged latencies of unilateral clicks
      vestibular-evoked myogenic potentials also showed latency prolongation in
      bilateral clicks vestibular-evoked myogenic potentials. CONCLUSION: Although the
      use of bilateral acoustic stimulation shortens the vestibular-evoked myogenic
      potential latencies in normal subjects, it does not affect the bilateral clicks
      vestibular-evoked myogenic potential ability to detect retrolabyrinthine lesions.
      Bilateral clicks vestibular-evoked myogenic potentials are a more convenient mode
      with which to help diagnose both labyrinthine and retrolabyrinthine lesions than
      unilateral clicks vestibular-evoked myogenic potentials.

PMID- 16436990
TI  - The molecular biology of vestibular schwannomas: dissecting the pathogenic
      process at the molecular level.
AB  - OBJECTIVE: The goal of this article was to review concisely what is currently
      known about the tumorigenesis of vestibular schwannomas. BACKGROUND: Recent
      advances in molecular biology have led to a better understanding of the cause of
      vestibular schwannomas. Mutations in the neurofibromatosis type 2 tumor
      suppressor gene (NF2) have been identified in these tumors. In addition, the
      interactions of merlin, the protein product of the NF2 gene, and other cellular
      proteins are beginning to give us a better idea of NF2 function and the
      pathogenesis of vestibular schwannomas. METHODS: Review of the relevant basic
      science studies at our institution as well as the basic science and clinical
      literature. RESULTS: The clinical characteristics of vestibular schwannomas and
      neurofibromatosis type 2 syndromes are reviewed and related to alterations in the
      NF2 gene. Studies demonstrating our current understanding of tumor developmental
      pathways are highlighted. In addition, methods of clinical and genetic screening
      for neurofibromatosis type 2 disease are outlined. Avenues for the development of
      potential future research and therapies are discussed. CONCLUSION: Great strides
      have been made to identify why vestibular schwannomas develop at the molecular
      level. Continued research is needed to find targeted therapies with which to
      treat these tumors.

PMID- 16436991
TI  - Intratumoral and brainstem hemorrhage in a patient with vestibular schwannoma and
      oral anticoagulant therapy.
AB  - OBJECTIVE: To report the first case of spontaneous intratumoral and brainstem
      hemorrhage in a patient with a vestibular schwannoma. STUDY DESIGN: Case report
      and review of the literature. SETTING: University-based, tertiary referral
      center. PATIENT: A 73-year-old woman with a vestibular schwannoma, anti-vitamin K
      overdose, and arterial hypertension experienced a rapid onset of headache, facial
      palsy, diplopia, and hoarseness. INTERVENTIONS: The patient was admitted to the
      intensive care unit and treated with vitamin K and corticoids. MAIN OUTCOME
      MEASURES: Clinical and radiologic findings. RESULTS: At admission, the magnetic
      resonance imaging and computed tomographic scans showed an intratumoral
      hemorrhage. The patient entered a coma 24 hours after the onset of the symptoms.
      At that time, the computed tomographic scan demonstrated a massive intratumoral
      and brainstem hemorrhage. The patient died 3 days later. CONCLUSION:
      Intratumoral, subarachnoid, and brainstem hemorrhages can occur in patients with
      vestibular schwannoma. Oral anticoagulant therapy is a risk factor for tumor
      related hemorrhage.

PMID- 16436992
TI  - Microsatellite analysis of recurrent vestibular schwannoma (acoustic neuroma)
      following stereotactic radiosurgery.
AB  - HYPOTHESIS: Genetic and immunohistochemical studies may provide insight into the
      mechanisms of vestibular schwannoma (VS) recurrence following radiation therapy.
      BACKGROUND: Stereotactic radiation therapy is an increasingly common alternative
      to microsurgical resection for the primary management of sporadic VS. The
      molecular mechanisms associated with recurrent vestibular schwannoma (VS)
      following radiation therapy are not known. METHODS: Primary or irradiated VS
      tumors were fresh-frozen at the time of surgical resection and microdissected to
      undergo DNA extraction. Lymphocytic control DNA was isolated from blood obtained
      by venipuncture. Paired normal and tumor DNA specimens were analyzed for allelic
      loss by PCR amplification of polymorphic dinucleotide repeat sequences.
      Immunohistochemical studies were performed on paraffin-embedded, irradiated
      surgical specimens. RESULTS: Using 16 polymorphic microsatellite markers, 20 of
      26 non-irradiated VS demonstrated loss of heterozygosity (LOH) in at least one
      locus of chromosome 22q. In contrast, none of the four irradiated recurrent VS
      demonstrated LOH on chromosome 22q (p = 0.008). No allelic loss was seen in
      either the primary or irradiated VS utilizing markers mapping to chromosome 10.
      Deletions on chromosome 10 are seen in both benign and higher-grade meningiomas
      and intracranial malignancies associated with radiotherapy. Immunohistochemical
      studies were performed to detect the protein product of the NF2 gene, merlin, in
      the four irradiated VS. NF2 staining was not observed. CONCLUSION: This study
      represents the first microsatellite and immunohistochemical analysis of recurrent
      VS following radiation therapy. Our preliminary observations suggest an
      alternative mechanism of NF2 inactivation that may correlate with radioresistance
      in VS.

PMID- 16436993
TI  - The prevalence and onset of gaze modulation of tinnitus and increased sensitivity
      to noise after translabyrinthine vestibular schwannoma excision.
AB  - OBJECTIVE: To determine the prevalence and timing of onset of gaze-modulated
      tinnitus and increased sensitivity to noise in patients who had undergone
      translabyrinthine excision of a vestibular schwannoma. STUDY DESIGN:
      Retrospective questionnaire study. SETTING: University hospital departments of
      audiology and neurotology. PATIENTS: A cohort of 359 patients who had undergone
      translabyrinthine excision of a vestibular schwannoma in the period 1997 to 2003.
      INTERVENTION: Translabyrinthine excision of a unilateral sporadic vestibular
      schwannoma. MAIN OUTCOME MEASURES: Patient reports and visual analogue scale
      measures of the timing of onset of gaze-modulated tinnitus and the presence,
      timing of onset, and persistence of increased sensitivity to noise after surgery.
      RESULTS: Completed questionnaires were returned by 275 patients (77%), of whom
      132 (48%) were men and 143 (52%) were women. Preoperative tinnitus was reported
      in 150 patients (55%). In 124 of these 150 (83%) the tinnitus persisted, and in
      26 of 150 (17%) it abated. Of the 125 patients without preoperative tinnitus, 43
      (34%) developed it postoperatively. In 167 (61%) patients of the total group of
      275, postoperative tinnitus was reported. Gaze-modulated tinnitus was reported in
      53 patients (19%). Somatic-evoked or -modulated tinnitus was reported in 38
      patients (14%). In response to the question, "Did you notice being extra
      sensitive to noise after your operation?," 138 patients (50%) replied that they
      did. In 111 patients, this persisted. The onset of the modulation of tinnitus was
      distributed throughout the postoperative period, whereas the onset of increased
      sensitivity to noise was overwhelmingly in the first 2 months after surgery.
      CONCLUSION: Gaze modulation of tinnitus after vestibular schwannoma removal was
      identified in 19% of patients in this series. The onset data did not convincingly
      argue for any specific mechanism. The prevalence of increased sensitivity to
      noise is surprising and may represent central hyperacusis in response to
      unilateral deafferentation of the auditory system.

PMID- 16436994
TI  - Revision lateral skull base surgery.
AB  - OBJECTIVE: To describe functional and reconstructive results after revision
      lateral skull base surgery with comparison of benign and malignant lesions. STUDY
      DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS:
      All patients undergoing revision surgery for benign and malignant lateral skull
      base tumors. INTERVENTIONS: Surgical resection of recurrent lateral skull base
      tumors and reconstruction of resulting defects. MAIN OUTCOME MEASURES: Cranial
      nerve function postoperative complications. RESULTS: Forty operations for
      recurrent lateral skull base tumors occurred between January 1, 1987, and
      December 31, 2003, with follow-up of at least 1 year. Thirty-three operations
      were for benign lesions, 27 of which were glomus tumors. Seven operations were
      for malignant tumors. Fifty-eight percent of patients had preoperative cranial
      nerve deficits (66% of benign tumors and 14% of malignancies). The most common
      preoperative deficit occurred in the Xth cranial nerve. Postoperative cranial
      nerve deficits were seen in 95% of patients and multiple nerve deficits were seen
      in 75%. The most common postoperative deficits were observed in the IXth and Xth
      cranial nerves. Thirty-one patients had one previous procedure, six had two
      previous procedures, and three had three previous procedures. Abdominal fat and
      temporoparietal fascia were the most common reconstruction materials. There was
      one case of meningitis, two cerebrospinal fluid leaks, and one pseudomeningocele.
      There was one recurrent adenoid cystic tumor resulting in death and two partially
      resected glomus tumors. Subsequent procedures are discussed. CONCLUSION:
      Postoperative cranial deficits are more common after revision skull base surgery
      than after primary surgery. Complete resection without recurrence can be expected
      for revision skull base surgery. Modern reconstruction techniques reduce major
      postoperative complications and morbidity from cranial nerve deficits.

PMID- 16436995
TI  - Hearing preservation and facial nerve outcomes in vestibular schwannoma surgery:
      results using the middle cranial fossa approach.
AB  - OBJECTIVE: To evaluate surgical results using the middle cranial fossa approach
      for hearing preservation vestibular schwannoma surgery. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral academic center. PATIENTS:
      Seventy-three consecutive patients with vestibular schwannoma operated on using
      the middle cranial fossa approach between February 1999 and February 2005.
      INTERVENTIONS: The tumors were removed via the middle cranial fossa approach with
      modifications to improve exposure. Standard auditory brainstem and facial nerve
      monitoring were used. MAIN OUTCOME MEASURES: Pre- and postoperative hearing
      measures and facial function, tumor size, and postoperative complications.
      Hearing status was categorized into Classes A, B, C, and D as described by the
      American Academy of Otolaryngology-Head and Heck Surgery "Guidelines for the
      Evaluation of Hearing Preservation in Acoustic Neuroma, 1995." RESULTS: Thirty
      four patients presented with Class A hearing preoperatively. Among patients
      presenting with Class A hearing, a total of 27 (80%) maintained Class A or B
      hearing postoperatively. Of these, 21 (62%) remained in Class A, 6 (18%)
      deteriorated slightly to Class B, and 7 (20%) deteriorated to Class D
      postoperatively. Twenty-eight patients presented with Class B hearing
      preoperatively. Of these, 18 (64%) remained in Class B, 3 (11%) deteriorated to
      Class C, and 7 (25%) deteriorated to Class D. Three patients had Class C hearing
      preoperatively. Of these, 2 (66%) remained in Class C and 1 (33%) deteriorated to
      Class D. Eight patients presented in Class D and one of these improved to Class C
      postoperatively. Overall, 62 patients presented with useful (Class A or B)
      hearing and 45 (73%) remained in Class A or B. Nineteen patients had tumors
      larger than 10 mm in greatest dimension and had Class A or B hearing
      preoperatively. Of these, 11 (58%) retained Class A or B hearing postoperatively.
      At 4 months or greater follow-up, facial nerve outcome were excellent in 96%:
      House-Brackmann Grade I in 61 (85%), Grade II in 8 (11%), and Grade III in 3
      (4%). There were no Grade IV, V, or VI results on final follow-up. Six (8%)
      patients developed cerebrospinal fluid leaks. CONCLUSION: By achieving excellent
      exposure and using meticulous microsurgical technique, it is possible to resect
      small vestibular schwannomas via the middle fossa approach, with preservation of
      hearing at excellent or preoperative levels in the majority of patients, with
      excellent or satisfactory facial nerve outcomes in 96% of patients.

PMID- 16436996
TI  - Squamous cell carcinoma of the external auditory canal and middle ear: an
      operation combined with preoperative chemoradiotherapy and a free surgical
      margin.
AB  - OBJECTIVE: Treatment outcomes for squamous cell carcinoma of the temporal bone
      were evaluated regarding stage, therapeutic strategy, and prognostic factors.
      STUDY DESIGN: Retrospective case review. SETTING: University hospital and
      outpatient clinic. PATIENTS: Twenty-five patients with primary squamous cell
      carcinoma of the external auditory canal and middle ear. INTERVENTION:
      Preoperative chemoradiotherapy and radiotherapy were used in 7 of 12 patients.
      Lateral temporal bone resection was performed for the lesions not beyond the
      tympanic membrane. Subtotal temporal bone resection was chosen for lesions
      extending to the middle ear cavity when there was no invasion to the pyramidal
      apex, carotid canal, or dura or metastasis. Others were conservatively treated by
      chemoradiotherapy. When the performance status was poor or an agreement regarding
      the operation could not be reached, the treatment was modified. MAIN OUTCOME
      MEASURE: Estimated survival rates. RESULTS: The 3-year estimated survival for T1
      and T2 lesions was 100%. The 5-year estimated survival for T3 and T4 lesions was
      80% and 35%, respectively. The 5-year estimated survival improved up to 75% for
      T4 tumors with operation and 16% for those without operation after 47 months. The
      tumor-free surgical margin is significantly related to patient survival in T3 and
      T4 lesions. Multivariate analysis predicted that concomitant chronic otitis media
      and positive lymph nodes were significantly associated with poorer survival.
      CONCLUSION: The tumor-free surgical margin was important to survival. When T4
      lesions did not involve the pyramidal apex, carotid canal, dura, or any lymph
      nodes, the surgical intervention improved the estimated survival rate to a level
      as good as T3 lesions.

PMID- 16436997
TI  - Treatment of culture-negative skull base osteomyelitis.
AB  - OBJECTIVE: To evaluate the efficacy of a therapeutic regimen in the treatment of
      patients with culture-negative skull base osteomyelitis. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Eight
      patients with diabetes mellitus presented with otalgia and were found to have
      positive technetium and gallium scans of the temporal bone. These patients,
      however, all had negative cultures of their external auditory canals. All
      patients had been treated with ototopic drops and two patients had undergone a 2
      week course of oral quinolones. INTERVENTIONS: All patients were treated with a 6
      week course of intravenous ceftazidime or aztreonam for penicillin-allergic
      patients, oral ciprofloxacin at a higher dose than normal, and topical
      aminoglycoside steroid drops. MAIN OUTCOME MEASURES: Resolution of the temporal
      bone gallium scan abnormality, recurrence rate, and time to discharge from the
      hospital. RESULTS: The patients were discharged from the hospital within 4 days
      from admission. All patients showed resolution of the temporal bone abnormality
      on the gallium scan at the 6-week time point. The median follow-up period was 6
      months, and none of the patients had a recurrence of the infection. CONCLUSION:
      The above-described treatment regimen will result in a high cure rate and a short
      hospitalization period.

PMID- 16436998
TI  - Thickness distribution of fresh and preserved human eardrums measured with
      confocal microscopy.
AB  - HYPOTHESIS: In this study, the thickness distribution of the fresh human eardrum
      was measured and possible thickness changes in successive stages of preservation
      and preparation were studied. METHODS: The thickness measurement was performed on
      axial fluorescence images taken perpendicularly through the membrane with a
      confocal microscope. The influence of fixation and preservation (in Cialit
      solution) on the thickness was also investigated. The same eardrum was prepared
      (decalcified, dehydrated, and stained) for histologic sectioning and the
      thickness was measured on the sections using conventional light microscopy.
      RESULTS: Similar thickness distributions in the measured samples (n = 3) were
      observed. The pars tensa has a rather constant thickness in a central region
      curving as a horseshoe upward around the manubrium. The membrane thickens
      slightly from the inferior to the superior side. The anterior region is thicker
      than the posterior region. In narrow bands along the manubrium, peripheral rim,
      and in the region inferior to the umbo, a much larger thickness in comparison
      with that in the central region was found. Mean thicknesses of approximately 40,
      50, and 120 microm were observed in the central region of the studied eardrums,
      respectively. CONCLUSION: Whereas the thickness distribution of the human
      eardrums shows similar features, the absolute thickness seems to vary a lot from
      one specimen to another. There is no significant difference in thickness of the
      same membrane in fresh, fixed, or preserved condition. Thus, human eardrums may
      be safely preserved in fixative for later thickness measurements. The histologic
      preparation process, however, causes a significant location-dependent shrinkage.

PMID- 16436999
TI  - Mitigation of hearing loss from semi-circular canal transection in pseudomonas
      otitis media with ciprofloxacin-dexamethasone irrigation.
AB  - HYPOTHESIS: Irrigation of the mastoid with a quinolone antibiotic-steroid
      solution may mitigate hearing loss caused by iatrogenic semicircular canal injury
      in the presence of Pseudomonas aeruginosa (PA) otitis media (OM). BACKGROUND:
      Studies have shown the cochlea to be more vulnerable to semicircular canal
      transection (SCT)-related hearing loss in the presence of PA OM. Prophylactic
      systemic antibiotics and steroids may decrease this hearing loss, but SCT is
      usually not planned. The aim of this study was to determine if irrigation with
      ciprofloxacin-dexamethasone (cipro-dex) could improve hearing outcomes following
      SCT in PA OM. METHODS: PA OM was induced in 28 animals. After three to five days,
      unilateral SCT was performed in each animal, with sham SCT on the contralateral
      ear. At surgery, half of the animals (n = 14) underwent irrigation of the both
      mastoid bullae with cipro-dex; the second group of animals (n = 14) underwent
      irrigation of the bullae with sterile saline. Auditory thresholds were obtained
      immediately prior to SCT and 7-10 days after SCT. RESULTS: SCT ears treated with
      cipro-dex showed a mean click threshold improvement of 4.6 dB from pre
      transection to 7-10 days post-transection, whereas thresholds in the SCT ears
      treated with saline worsened by 7.5 dB (p = 0.15). CONCLUSION: Irrigation of the
      guinea pig bulla with cipro-dex following SCT in the setting of PA OM appears
      safe and may yield beneficial effects on hearing.

PMID- 16437000
TI  - Innervation of the apical turn of the human cochlea: a light microscopic and
      transmission electron microscopic investigation.
AB  - HYPOTHESIS: A light and transmission electron microscopic investigation of the
      apical turn of a freshly fixed human cochlea. BACKGROUND: Our knowledge about the
      human cochlea rests to a large extent on animal species research. An opportunity
      to obtain tissue from normal-hearing persons occurs during surgery for life
      threatening petroclival meningioma. This study presents detail on the morphology
      and innervation of the apical part of the human cochlea using light microscopic
      and transmission electron microscopic level sectioning. METHODS: The tissue was
      histologically processed after removal during petroclival meningioma surgery. The
      cochlea was serially sectioned perpendicularly to its long axis, and at regular
      distances semithin sections were reembedded and prepared for transmission
      electron microscopy. Nerve fibers/fascicles were traced from the area of the
      spiral ganglion to the level of the inner hair cells, and a cochleotopic "map" of
      the cochlear nerve supplying the apical portion was constructed. RESULTS: The
      apical turn was found to be innervated by 3,694 myelinated nerve fibers
      representing approximately 10% of the total number of fibers innervating the
      cochlea. The total number of unmyelinated nerve fibers was 513. The majority
      belonged to the efferent olivocochlear system and the intraganglionic spiral
      bundle or represented Type II afferent neurons innervating outer hair cells.
      CONCLUSION: The significance of the anatomic findings in relation to cochlear
      implantation is discussed.

PMID- 16437001
TI  - Adam Politzer (1835-1920) and the description of otosclerosis.
AB  - In 1893, Adam Politzer was the first to describe otosclerosis as a specific
      disease fixating the stapes. The aim of this study is to follow Politzer's
      research to understand how he finally explained the mechanism responsible for the
      fixation of the stapes. Politzer conducted his preliminary research from 1862 to
      1893. From the concept of a dry catarrh of the middle ear, the fixation of the
      stapes became progressively associated with a specific ossification in and around
      the footplate. Politzer presented his first results in 1893. He completed his
      research by concluding in 1901 that otosclerosis had become an independent
      disease and should have the right to its own chapter in otologic books. He
      selected the word otosclerosis to describe this new pathologic entity.

PMID- 16437002
TI  - Congenital cholesteatoma isolated to the mastoid.

PMID- 16437003
TI  - Cochlear fistula in recurrent cholesteatoma.

PMID- 16437004
TI  - Stria vascularis hearing loss.

PMID- 16437008
TI  - Integrins in growth plate cartilage.
AB  - The growth plate is a highly specialized layer of cartilage where chondrocytes
      proliferate and differentiate in order to bring forth longitudinal bone growth.
      Interaction of cells with the extracellular matrix significantly influences
      differentiation and growth. These processes involve integrin as well as
      nonintegrin cell surface receptors, like annexin V and CD44. In chondrocytes,
      which are surrounded by abundant matrix, tissue integrity and cell survival
      depend on well-tuned interactions of cells and ECM. In the field of growth
      research, besides classical growth stimulating factors acting via endocrine
      pathways, investigations on local determinants of cell differentiation and
      survival play an important role. This review describes the role and function of
      integrins, their occurrence in growth plate cartilage and their possible
      involvement in differentiation during growth.

PMID- 16437009
TI  - Rational use of insulin analogues in the treatment of type 1 diabetes mellitus.
AB  - Long-term near-normoglycaemia in Type 1 diabetes protects against the onset
      and/or progression of microangiopathic complications. To successfully reach the
      goal while avoiding the risk of hypoglycaemia and hypoglycaemia unawareness,
      insulin therapy has to be physiological. Mealtime insulin should be given as a
      bolus injection before, or both before and after, a meal. In addition, basal
      insulin between meals should be replaced by an insulin preparation with a square
      wave action profile. Rapid-acting insulin analogues are the mealtime insulin
      preparations of choice. Either continuous subcutaneous insulin infusion (CSII),
      or once day injection of the long-acting insulin analogue glargine is required to
      optimally replace basal insulin. In Type 1 diabetes the benefits of mealtime
      treatment with rapid-acting insulin analogues become apparent only to the extent
      to which replacement of basal insulin is optimised at the same time. This has
      been difficult in the past with the peak insulin NPH, but it is nowdays easier
      with the nearly peakless long-acting insulin analogue glargine. As compared to
      NPH, glargine reduces the risk for nocturnal hypoglycaemia, and at the same time
      improves HbA1c similarly to CSII.

PMID- 16437010
TI  - The association between autoimmune thyroiditis, autoimmune gastritis and type 1
      diabetes.
AB  - Type 1 diabetes mellitus (DM1), autoimmune thyroid disease (ATD) and autoimmune
      gastritis often occur together forming the so-called autoimmune polyendocrine
      syndrome (APS) type 3. Thyroid autoimmunity is evident in up to one third and
      gastric autoimmunity in up to a quarter of patients with DM1. Also relatives of
      DM1 patients, particularly mothers, have higher frequencies of these autoimmune
      conditions. Vice versa, gastric autoimmunity is present in one third of ATD
      patients and islet autoimmunity in one out ten. The BB-DP rat, the NOD mouse, the
      OS chicken and the neonatal thymectomy mouse model are animal models of APS type
      3. In these models the autoimmune destruction of the various target tissues has
      been shown to be a multi-step process in which several genetic polymorphisms need
      to converge to induce both local anomalies in the target gland and anomalies in
      the immune system. With regard to environmental factors, excess iodine is well
      known to elicit/aggravate thyroid autoimmunity in these animal models. Screening
      DM1 patients and their relatives (particularly females) for thyroid autoimmunity
      is recommended. If positive, excess iodine should be avoided and thyroxin
      treatment considered. Whether autoimmune thyroiditis and autoimmune gastritis
      patients should be screened for islet Ab is not clarified.

PMID- 16437011
TI  - Developing circadian rhythmicity in infants.
AB  - Circadian rhythms are endogenously generated rhythms with a period length of
      about 24-hrs. Evidence gathered over the past decade indicates that the circadian
      timing system develops prenatally and the suprachiasmatic nuclei, the site of a
      circadian clock, are present by mid-gestation in human and non-human primates.
      Recent evidence also shows that the circadian system of primate infants is
      responsive to light at very premature stages and that low intensity lighting can
      regulate the developing clock. After birth, there is progressive maturation of
      the circadian system outputs, with pronounced rhythms in sleep-wake and hormone
      secretion generally developing after two months of age. With the continued
      elucidation of circadian system development and influences on human physiology
      and illness, it is anticipated that consideration of circadian biology will
      become an increasingly important component of neonatal care.

PMID- 16437012
TI  - Endocrine abnormalities in Anorexia Nervosa.
AB  - Anorexia Nervosa (AN) is a psychiatric disorder characterized by the classic
      triad: amenorrhea, weight loss, and behavioral changes. It is generally seen in
      young, white women under 25 and is particularly common in adolescence. The
      mortality of the disease varies between 5.1% and 13%. The endocrine changes
      associated with AN have been studied in depth and provide strong evidence for
      hypothalamic dysfunction. All are secondary and reverse with weight gain. In
      general, gonadotropin (FSH, LH) levels are decreased in patients with AN, as well
      as the response to Gonadotropin releasing hormone (GnRH). Fasting growth hormone
      levels are elevated, but the stimulated response of Growth hormone (GH) to Growth
      hormone releasing hormone (GHRH) is normal and inversely correlated to body
      weight. Serum Growth hormone binding protein (GHBP), insulin growth factor I (IGF
      I) and IGF binding protein (IGFBP) - 3 levels are all significantly decreased in
      patients with AN and return to normal with refeeding. IGFBP-1 and 2 are increased
      and return also to normal with weight gain. Serum IGF-II is decreased but not
      significantly. The IGFBP-3 proteolytic activity is normal. Thyroxine (T4) and
      Triiodothyronine (T3) while reverse T3 (rT3) is elevated. Thyrotropin stimulating
      hormone (TSH). TSH levels are normal with a delayed response to thyrotropin
      releasing hormone (TRH). Cortisol levels are normal or elevated as well as
      urinary free cortisol. Corticotropin (ACTH) levels are normal with decreased
      response to Corticotropin releasing hormone (CRH). Dexamethasone suppression test
      is abnormal. Sex steroids are decreased. Finally leptin levels are decreased in
      patients with AN while ghrelin levels are elevated. Both leptin and ghrelin
      levels return to control values after renutrition.

PMID- 16437014
TI  - Technological advances in the treatment of diabetes mellitus: better
      bioengineering begets benefits in glucose measurement, the artificial pancreas,
      and insulin delivery.
AB  - The management of type 1 diabetes is being advanced by innovations in glucose
      measurement, development of an artificial pancreas, and in alternate routes of
      insulin delivery. Emerging technologies will allow insulin to be delivered more
      effectively. In the future, patients with type 1 diabetes will receive insulin in
      optimal quantities (because of more information about blood glucose values) at
      optimal times (because of better integration of blood glucose values with
      appropriate insulin dosages) by way of optimal routes into the body (because of
      needle-free routes of administration) in order to achieve optimal blood glucose
      control. Emerging technologies for improved care of patients with type 1 diabetes
      include: 1. new methods for monitoring glucose, including noninvasive, minimally
      invasive, continuous, and alternate site measurement technologies; 2. new methods
      for integrating glucose values and insulin dosages, known as the artificial
      pancreas; and 3. new routes of insulin administration, including inhaled, oral,
      buccal, nasal, and transdermal drug delivery systems. These new technologies will
      facilitate proper treatment of type 1 diabetes and improve the lives of affected
      patients.

PMID- 16437015
TI  - Alpha-melanocyte stimulating hormone in modulation of inflammatory reactions.
AB  - Although adrenal stimulatory effects of ACTH and pigmentary influences of MSH
      have been known for decades, it has become clear only recently that melanocortin
      peptides have multiple effects upon the host. These effects range from modulation
      of fever and inflammation to control of food intake, autonomic functions, and
      exocrine secretions. Recognition and cloning of melanocortin receptors (MCRs) has
      greatly improved understanding of peptide-target cell interactions. Synthetic
      melanocortins, with selective affinities for specific MCRs, could be the basis
      for new classes of therapeutic molecules. This review examines promising targets
      for a-MSH and closely related peptides in inflammatory disorders.

PMID- 16437016
TI  - Lipoprotein(a) in children and adolescence.
AB  - Lipoprotein(a) [Lp(a)], an LDL-like lipoprotein, has an additional carrier
      protein - apo (a), which closely resembles plasminogen. Epidemiological and
      experimental studies provide overwhelming evidence that Lp(a) may promote
      atherogenesis and thrombosis via its LDL-like and plasminogen-like mechanisms.
      With more than 90% variance explainable by the apo(a) gene, Lp(a) is detectable
      at birth and increases with age until adolescence when the Lp(a) reaches adult
      levels. There is a striking close offspring-parental correlation in Lp(a) levels,
      which is present at birth and tracks for life. While Lp(a) levels are highly
      regulated genetically and difficult to change, it appears that factors during the
      first year of life may have more impact on Lp(a) expression profiles, which
      possibly have long-lasting effects. Lp(a) levels are elevated in children with
      obesity, diabetes, renal diseases, hypercholesterolemia and are predictive of
      vascular diseases in themselves and other family members. We suggest that Lp(a)
      should be routinely measured in both children and adults for vascular disease
      risk factor assessment, at least among those with high conventional Coronary
      Artery Disease (CAD) risk factors and those with established CAD.

PMID- 16437017
TI  - Resistance training, skeletal muscle and growth.
AB  - Resistance training in youth and its effectiveness, possible effect on growth and
      safety considerations, has received considerable public and scientific attention
      in recent years. Although few early studies questioned the usefulness of
      resistance training in children, numerous recent studies have demonstrated its
      effectiveness in both children and adolescents. Nevertheless, the optimal
      intensity and volume of training for youths of different ages requires further
      study. The increase in strength following resistance training in youths,
      especially in prepubertal children, is believed to be due mainly to neural
      adaptations and only minimally, if at all, to muscle hypertrophy. Few studies
      have examined the long-term effect of resistance training on growth. The few
      which have, found that, contrary to the common misconception that resistance
      training may retard growth. Scientific evidence indicates that resistance
      training results in increased serum IGF-I and that there is no detrimental effect
      on linear growth. Finally, numerous studies have demonstrated that with
      appropriate supervision and precautions, resistance training can be safe and
      effective for children and adolescents.

PMID- 16437018
TI  - Testicular torsion in the pediatric age group: diagnosis and treatment.
AB  - PURPOSE: To review and update several aspects of testicular torsion. INCIDENCE:
      The relative incidence of testicular torsion, torsion of testicular appendix and
      epididymo-orchitis is variable and depends on mode of diagnosis and patients'
      age. AGE: Testicular torsion can occur at any age. The peak is in adolescents
      below the age of 18 years. SYMPTOMS: Classical symptoms are not always present.
      Range of duration is varied. Nausea and vomiting are positive predictive value
      for testicular torsion. PHYSICAL EXAMINATION: Main findings predicting testicular
      torsion are absence of cremasteric reflex and diffuse tenderness. IMAGING: Color
      Doppler Ultrasound can assess in equivocal and low clinical suspicious conditions
      for testicular torsion. NEONATAL TORSION: There are two conditions in this age
      group; the prenatal that urgent exploration is in controversy and postnatal that
      urgent surgery is required. LATE OUTCOME: Early salvage rate and late atrophy
      depends on duration and degree of torsion. MEDICOLEGAL: Testicular torsion is an
      active area of malpractice litigation. Late presentation and atypical
      presentations do not affect the medicolegal outcome.

PMID- 16437020
TI  - The role of genetics in pediatric endocrinology.
AB  - Information on the genetics of endocrine disorders and genetic testing is
      increasing rapidly. This makes it important for endocrinologists to be able to
      efficiently search for clinically relevant information and to access specialized
      laboratory testing and genetics professionals to assist with diagnosis,
      education, counseling and management of patients and families. Because new
      findings are reported in many different publications, current comprehensive
      information on clinical and laboratory findings of and genetic testing for
      endocrine disorders cannot be found in any single journal or text. Electronic
      databases provide rapid access to such information. Endocrinologists need to
      develop a working understanding of these databases. This review examines
      principles of inheritance, types of genetic variation and the genetic aspects of
      selected endocrine disorders. It demonstrates how information on genetics and
      genetic testing can be obtained and discusses how endocrinologists and
      geneticists can work together to strengthen the clinical applications of genetics
      to pediatric endocrinology.

PMID- 16437021
TI  - Molecular aspects of female and male gonadal development in mammals.
AB  - In mammals, the choice between male or female development is genetically
      determined. Sex determination takes place when the embryonic gonad becomes either
      a testis or an ovary. This process is directed by genes that have been discovered
      by genetic analysis of sex-reversed patients and confirmed by knock-out
      experiments in mice. The testis-determining pathway is better known than the
      ovary pathway. SRY, a gene located on the Y chromosome, triggers a complex
      genetic cascade leading to testicular differentiation. In this cascade, two genes
      play a crucial role in male differentiation, SOX9 and FGF9, which contribute to
      testicular cord formation. However, only a minority of 46,XY sex-reversed
      patients can be explained by mutations in known genes such as SRY, SOX9, WT1 and
      SF1, suggesting that other genes influencing sex determination are yet to be
      discovered. In females, some rare genes that induce ovarian failure or female-to
      male sex-reversal, have been found through gene-targeted inactivation in mice or
      positional cloning of mutations in humans and goats. In both sexes, genetic
      analysis of sex-reversed individuals (XX males, XX and XY hermaphrodites and XY
      with complete or partial dysgenesis) remains an approach of choice to isolate new
      genes involved in sex determination.

PMID- 16437022
TI  - Hypospadias: pathophysiology and etiologic theories.
AB  - Hypospadias is a congenital defect of the male urethra and phallus. Most boys
      with hypospadias have no other signs of under-masculinization or congenital
      malformations. The incidence appears to be increasing in the developed world.
      Evidence suggests that the etiology of hypospadias is multifactorial and that
      environmental conditions may have a role in the increasing incidence. The authors
      review normal male urethral development, epidemiology and the role of maternal
      fetal hormone interactions, androgen synthesis, 5alpha-reductase, androgen
      receptor, environmental factors and assisted reproductive technology.

PMID- 16437023
TI  - The pathogenesis of insulin resistance in children: metabolic complications and
      the roles of diet, exercise and pharmacotherapy in the prevention of type 2
      diabetes.
AB  - In this manuscript we discuss the pathogenesis of type 2 diabetes in children,
      emphasizing the central importance of obesity, insulin resistance, dyslipidemia,
      hypertension and endothelial dysfunction. We then review critically the benefits
      of diet, exercise and pharmacotherapy in preventing type 2 diabetes and vascular
      complications in high risk children and young adults.

PMID- 16437024
TI  - Adipotoxicity and the insulin resistance syndrome.
AB  - During the last decades, nutritional fat intake has continuously inflated in
      parallel with an enormous rise in the prevalence of obesity and type-2 diabetes
      in adults but increasingly also in adolescents and even children. Augmented fat
      intake is associated with an increased mass of adipose tissue which releases free
      fatty acids (FFA) but also hormones and cytokines such as leptin, adiponectin,
      resistin, tumor necrosis factor-a and interleukin-6. In particular, FFA decrease
      insulin-mediated glucose transport/ phosphorylation in skeletal muscle and impair
      suppression of glucose production by the liver, indicating insulin resistance. In
      addition, ectopic lipid storage in both liver and skeletal muscle has recently
      been related to reduced insulin sensitivity. In conclusion, increased fat intake
      and expanded body fat are now held responsible for increased FFA availability and
      hormonal changes which may lead to insulin resistance and type- 2 diabetes.

PMID- 16437025
TI  - Bone mass evaluation in children - comparison between methods.
AB  - Peak adult bone mass should be optimized during childhood and adolescence. The
      physiology of bone mass accretion during these early years of life has been
      extensively studied, due to the development of reliable, precise, little or
      noninvasive methods of bone mass assessment. The purpose of this review is
      briefly to describe quantitative aspects of bone mass accretion during
      intrauterine life, childhood and adolescence and to describe the methods that
      have been used to assess bone mass in children in terms of precision, accuracy,
      ease of use, invasiveness and normative data. In particular, we review major
      methods such as radiographic methods, photon absorptiometry, dual-energy X-ray
      absorptiometry, quantitative ultrasound, quantitative computerized tomography and
      other methods less frequently used.

PMID- 16437026
TI  - Endocrine aspects of headaches in children and adolescents.
AB  - Headaches due to endocrine diseases in childhood are rare, but any child with
      chronic headaches should be given serious consideration. The most serious
      etiology is a tumor of the hypothalamic-pituitary region. Headaches can also
      occur as premenstrual migraine or as water retention due to glucocorticoid or
      Growth Hormone (GH) overdosage.

PMID- 16437028
TI  - IGF, IGF receptor and overgrowth syndromes.
AB  - The insulin-like growth factors are a family of growth factors, binding proteins
      and receptors that are involved in normal growth as well as in a number of
      pathological states. Overgrowth syndromes are a group of disorders characterized
      by a phenotype of excessive somatic and visceral growth. In addition, patients
      suffering from overgrowth syndromes are predisposed to develop cancer. Several
      specific defects linked to the insulin-like growth factor system were elucidated
      for a group of these disorders, including Simpson-Golabi-Behmel syndrome,
      Bannayan-Ruvalcaba-Riley syndrome and Beckwith-Wiedemann syndrome. The aim of
      this review is to examine recent data linking the phenotype of overgrowth
      syndromes, visceral growth and increased risk of neoplasia, with the molecular
      machinery of the IGF system.

PMID- 16437029
TI  - Genetic advances, biochemical and clinical features and critical approach to
      treatment of patients with X-linked hypophosphatemic rickets.
AB  - X-linked hypophosphatemic rickets (XLH) is an hereditary form of rickets due to
      isolated renal tubular phosphate wasting and impaired production of 1,25
      dihydroxyvitamin D [1,25(OH)2D]. XLH is caused by mutations in the PHEX
      (phosphate regulating gene with homology to endopeptidases) gene, which is
      located on Xp22.1. The pathogenetic mechanisms by which mutations in the PHEX
      gene cause XLH are not completely known. Hypophosphatemia associated with
      disproportionate short stature and bone deformities of the lower limbs are the
      main findings in XLH patients. Some studies have shown that conventional
      treatment with vitamin D metabolites, such as 1,25(OH)2D3 or 1 alpha
      hydroxyvitamin D3, combined with inorganic phosphate salts is able to improve
      serum phosphate concentrations and linear growth, as well as healing rickets.
      However, some patients may have poor beneficial effects by this therapy. On the
      other hand, some important treatment complications, such as hypervitaminosis D,
      nephrocalcinosis and secondary/tertiary hyperparathyroidism may occur during the
      current therapy. Despite conventional treatment, some patients may require
      surgical correction of bone deformities. In the light of the recent genetic
      advances the mechanisms that could be involved in the pathogenesis of XLH are
      discussed. Furthermore, the article reviews the effects of the medical treatment
      providing current recommendations for the management of XLH patients.

PMID- 16437030
TI  - Screening for subclinical complications in young type 1 diabetic patients:
      experience acquired in Brussels.
AB  - Clinical studies conducted since the 1970s by the pediatric diabetology group of
      the Free University of Brussels have demonstrated that screening for subclinical
      retinopathy, neuropathy and nephropathy should be started at puberty and at least
      3 years after the diabetes diagnosis. The goal is to detect early abnormalities
      responsible for subclinical disorders that can be reversed by improved metabolic
      control, thus preventing the occurrence of irreversible potentially
      incapacitating lesions. A 1974 retinal fluorescein angiography study showed that
      the development of microaneurysms, which are irreversible lesions, could be
      preceded by fluorescein leakage due to disruption of the blood-retinal barrier.
      Risk factors for early retinopathy include: duration of diabetes, age at
      diagnosis (with younger children having longer times to retinopathy), puberty and
      sex (with onset one year earlier in girls than in boys), long-term bad metabolic
      control over several years, high cholesterol levels and excessive body mass index
      (BMI). On the other hand, rapid improvement of diabetic control may worsen
      diabetic retinopathy (1985). Minimal EEG abnormalities were found in relationship
      to frequent and severe hypoglycemic comas and/or convulsions and retinopathy
      (1979). Desynchronization of action potentials in distal nerve fibers preceded
      conduction velocity slowing (1981). A single high glycated hemoglobin value was
      associated with peroneal motor nerve conduction slowing (1985), which was not
      observed in the femoral nerve (1987). Sympathetic skin response (1996) and
      statistical analysis of heart rate variability (2001) could have some interest
      for the diagnosis of early diabetic autonomic neuropathy. Early microproteinuria
      is of mixed origin, being both glomerular (microalbumin) and tubular (Beta2
      microglobulin). Exercise testing to exhaustion did not provide additional
      information than the basal excretion (1976). Microtransferrinuria (1984) and
      urinary acid glycosaminoglycans output (2001) could also be predictive markers of
      glomerular dysfunction. Physical training reduced exercise-related proteinuria by
      half (1988). High levels of serum lipoprotein (a) were not associated with the
      presence of subclinical complications (1996). On the other hand, ultra sensitive
      C-reactive protein could be an interesting indicator for the risk of developing
      early complications (2002). Poor metabolic control was associated with higher
      levels of triglycerides, total cholesterol, LDL cholesterol and apolipoprotein B
      (1990). Decreased gluthatione peroxidase, gluthatione reductase and of vitamin C
      levels, denoting moderate oxidative stress, were found (1996), although there was
      no evidence of increased LDL cholesterol peroxidation (1998). Erythrocytes
      exhibited increased glycolytic activity and neutrophils decreased migration in
      relationship with metabolic control (1992). The degree of metabolic control
      influenced serum triiodothyronine levels (1985), magnesium concentrations (1999)
      and infection by Helicobacter Pylori (1997). Insulin therapy could activate the
      complement pathway if intermediate and long-acting insulin preparations without
      protamine sulphate are used (1992) and provoke higher BMI in adolescents on 4
      insulin injections (1988). Well-being was inversely related to glycated
      hemoglobin levels (1997).

PMID- 16437031
TI  - Diabetic retinopathy and its relevance to paediatric age. An update.
AB  - Diabetic retinopathy is a frequent chronic complication of diabetes and may
      predict nephropathy and cardiovascular events. Development of proliferative
      lesions and/or macular edema indicates that a sight-threatening stage has been
      reached which, if left untreated, will almost inevitably evolve to blindness.
      Prevention of this feared outcome relies upon optimal control of blood glucose
      and, when hypertension is present, blood pressure. Besides, yearly screening by
      ophthalmoscopy and/or retinal photography should be carried out in all people
      with diabetes to identify those who have developed sight-threatening lesions.
      Though sight-threatening retinopathy is rarely reached during paediatric age, if
      anything because it takes many years to develop, the retina should be carefully
      monitored already during childhood and adolescence. "Florid" retinopathy and
      diabetic papillopathy are possible specific manifestations of retinopathy in
      diabetic patients during their early post-pubertal years. Pre-pubertal years,
      though suggested by some as protecting against diabetic retinopathy, may, in
      fact, contribute to and even be an independent risk factor for the development of
      proliferative lesions later in life. Apart from controlling glycaemia and blood
      pressure, ongoing phase 3 trials are evaluating new possible pharmacologic
      approaches to the prevention and treatment of retinopathy which, to this date,
      relies upon the hugely effective but destructive application of laser
      photocoagulation.

PMID- 16437032
TI  - Orthotopic liver transplantation (OLT): Contribution of diagnostic imaging and
      interventional radiology in preparing the transplantation and managing
      complications. Part 1: Indications, surgical technique, diagnostic imaging and
      interventional radiology before transplantation from cadaveric and living donor.

PMID- 16437033
TI  - Orthotopic liver transplantation (OLT): Contribution of imaging and
      interventional radiology in preparing the transplantation and managing
      complications. Part 2: Post-OLT complications and their treatment.

PMID- 16437034
TI  - Gastrointestinal stromal tumours: Pictorial review.
AB  - Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours
      of the alimentary tract. They normally involve the stomach, the small bowel, or
      the colon. Localisation within the oesophagus, rectum, mesentery, omentum, or
      retroperitoneum is less common. GISTs are immunohistochemically identified by the
      expression of the c-kit protein, which is not detected in other mesenchymal
      tumours. The role of imaging includes the detection (subjects with occult
      gastrointestinal bleeding, incidental recognition, etc.), characterisation,
      analysis of relations between mass and gastrointestinal wall, staging, prognostic
      assessment (recognition of signs of malignancy and unfavourable prognosis), and
      follow-up during specific treatment. Owing to the frequent exophytic growth of
      these lesions, differentiation of these tumours from nondigestive lesions of
      different nature is a common diagnostic problem. Imaging findings usually allow
      differentiation from gastrointestinal epithelial tumours but not from non
      epithelial tumours, for which histological confirmation is necessary, in part to
      verify potential response to therapy. Smaller lesions, which are usually benign,
      tend to be well-defined, relatively homogeneous, and with intraluminal growth.
      Larger lesions normally show well-defined or ill-defined margins, inhomogeneous
      density both on unenhanced and on contrast-enhanced scans, with combined
      intraluminal/extraluminal growth and a tendency to spread to surrounding
      structures. Internal attenuation is often necrotic or clearly fluid. Signs of
      high-grade GIST include liver metastasis, gastrointestinal wall infiltration,
      large volume, irregular surface, ill-defined margins, inhomogeneous enhancement
      and peritoneal spread. Recurrences usually share the appearance of the larger,
      primary malignant GIST.

PMID- 16437035
TI  - CT findings of secondary aorto-enteric fistulae.
AB  - PURPOSE: The aim of our study was to review CT findings concerning secondary
      aorto-enteric fistulae (AEF). In particular, we aimed to evaluate signs of
      contrast medium extravasation from the aortic graft into the bowel (active
      bleeding), in correlation with clinical and surgical reports. MATERIALS AND
      METHODS: Clinical and CT findings were retrospectively evaluated in 13 surgically
      proven cases of AEF. All patients underwent spiral CT examination with biphasic
      contrast technique, before and 30 and 80 seconds after intravenous injection of
      120-150 ml of contrast medium (Ultravist 370; flow rate 2.5-3 ml/sec). Late scans
      (240 seconds) were also acquired on surgical anastomoses. We used 3 mm (arterial
      phase) and 5 mm (venous phase) slices. RESULTS: At surgery, all 13 patients
      presented a communication between the bowel and the aortic graft. At CT
      examination, all 13 patients presented one or more CT signs indicating AEF
      (perigraft soft tissue, perigraft fluid, ectopic air or bowel wall thickening).
      Moreover, in 6 out of 13 patients, contrast medium extravasation from the aortic
      graft into the small bowel (active bleeding) was detected with CT. Detection of
      active bleeding was possible because CT examinations were performed without oral
      administration of contrast medium. CONCLUSIONS: CT is easily and readily
      available and provides an accurate evaluation of the aorta and surrounding
      retroperitoneal tissues. In our study we were able to identify the CT sign of
      active bleeding in more than a half of the patients with acute gastrointestinal
      bleeding (66%). Hence, we suggest that patients undergo CT examination without
      oral contrast medium administration in order to better appreciate the presence of
      active bleeding.

PMID- 16437036
TI  - Percutaneous renal artery embolisation of non-functioning allograft. Preliminary
      experience.
AB  - PURPOSE: Percutaneous renal artery embolisation has been introduced as an
      alternative to nephrectomy in patients with non-functioning allograft and Graft
      Intolerance Syndrome (GIS). The symptoms resulting from GIS include fever, local
      pain, hypertension and haematuria. MATERIALS AND METHODS: From April to October
      2003, five patients were treated using this technique. The intraparenchymal renal
      arteries were embolized by injection of calibrated tris-acryl gelatin
      microspheres of increasing size (from 100-300 to 700-900 microns) and occlusion
      was completed by the insertion of 5mm to 8mm steel coils into the renal artery.
      RESULTS: The procedure was well tolerated in all cases and no major complications
      occurred. In 3 patients GIS-related symptoms disappeared immediately. One patient
      required a second embolisation due to collateral circulation arising from a
      lumbar artery with resolution of symptoms. In the last case, the patient
      underwent nephrectomy because of septic fever. CONCLUSIONS: On the basis of our
      preliminary experience we believe that, in selected patients, percutaneous renal
      artery embolisation is an effective, repeatable and minimally invasive
      alternative to nephrectomy with no significant serious complications.

PMID- 16437037
TI  - Non-invasive evaluation of coronary calcium.
AB  - With the increasing diffusion of 4-row,16-row and 64-row multislice computed
      tomography scanners, widespread coronary calcium scoring has become possible in
      Europe. This relatively easy-to-perform test has a high sensitivity and low
      specificity for the detection of significant coronary artery stenosis, and may
      have an important role in the risk stratification for future coronary artery
      events in selected groups of patients, such as those immediately at risk. This
      study reviews the techniques available for coronary calcium scoring (electron
      beam tomography and multislice computed tomography) with their respective
      protocols, as well as their advantages and disadvantages. The methods for
      interpreting the results, the potential indications and the clinical applications
      of the techniques are also described.

PMID- 16437038
TI  - Steady state evaluation of aortic dissections: A feasibility study.
AB  - PURPOSE: One the main reasons for the limited use of MRI in the evaluation of
      aortic dissection in emergency conditions is its long execution time. The authors
      report their experience regarding a new MRI sequence that reduces execution time
      and avoids the use of contrast medium. MATERIALS AND METHODS: Eighteen
      haemodynamically stable patients with suspected (16 cases, 3 with confirmed
      diagnosis of aneurysm) or known aortic dissection (2 cases) underwent in
      emergency conditions 1.5T MRI with Steady-State sequence (Fast Imaging Employing
      Steady-State Acquisition: GRE 2D; TR 3.5, TE 1.6; Flip Angle 45, bandwidth 125,
      matrix 224x224, NEX 1, acquisition time per slice 7 s, thickness 6-8 mm, FOV 38;
      2D-GE breath-hold sequence requiring cardiac triggering). The results obtained
      were compared in terms of diagnostic accuracy and execution time with those of
      classical MRI examination (black blood T1, FSE T2 and 3D MR-angiography) or
      multislice CT. RESULTS: The diagnostic accuracy of MRI, both with Steady-State
      sequence and the ''classical'' technique, and multislice CT in the diagnosis of
      dissection or aneurysm is equal (100%), whereas execution time is 6, 25 and 6
      minutes, respectively. Multislice CT proved to be more accurate than Steady-State
      MRI in evaluating the renal parenchyma and the extension of the dissection to the
      renal arteries. CONCLUSIONS: The Steady-State MRI sequence provides a diagnosis
      of aortic dissection or aneurysmal dilatation in a short time and may represent a
      valuable alternative to CT in emergency settings, especially in patients with
      reported contraindications to iodinated contrast media.

PMID- 16437039
TI  - Low dose CT in early lung cancer diagnosis: Prevalence data.
AB  - PURPOSE: Lung cancer has a high mortality rate and its prognosis largely depends
      on early detection. We report the prevalence data of the study on early detection
      of lung cancer with low-dose spiral CT underway at our hospital. MATERIALS AND
      METHODS: Since the beginning of 2001, 519 asymptomatic volunteers have undergone
      annual blood tests, sputum tests, urinalyses and low-dose spiral CT. The
      inclusion criteria were age (=/> 55 years old), a history of cigarette smoking
      and a negative history for previous neoplastic disease. The diagnostic workup
      varied depending on the size and CT features of the nodules detected. RESULTS: At
      baseline, the CT scan detected nodules > 5 mm in 22% of subjects; the nodules
      were single in 42 and multiple in 71. In 53% of cases the findings were
      completely negative, while in 122 (23.4%) nodules with a diameter < 5 mm were
      detected. Six cases of lung cancer were identified, of which four were stage I,
      one stage was IIIB and one was stage IV with adrenal metastases. CONCLUSIONS: Our
      preliminary data on spiral CT as a potential new diagnostic tool for lung cancer
      screening, although less promising than the Japanese and ELCAP results, confirm
      the feasibility of the technique. Additional validation is, however, required.

PMID- 16437040
TI  - Congenital bronchial atresia (CBA). A critical review of CBA as a disease entity
      and presentation of a case series.
AB  - PURPOSE: To analyse the state of the art of diagnostic imaging in the rare
      disease entity known as congenital bronchial atresia (CBA) and to suggest new
      guidelines for diagnosis. MATERIALS AND METHODS: From January 2002 to December
      2003 we examined 6 patients, 4 males and 2 females. Four of them complained of
      relapsing bronchitis; one patient was admitted with a diagnosis of pulmonary
      abscess. All patients underwent chest X-ray and MDCT. RESULTS: Five patients
      presented at chest x-ray the typical association of hilar mass and distal
      parenchymal hyperinflation that raised the suspicion of CBA; the remaining
      patient presented an area of parenchymal translucency that prompted us to perform
      MDCT, which showed severe stenosis of the segmental bronchus. CBA involved the
      left upper lobe (LUL) in 4 patients and the right upper lobe (RUL) in the
      remaining 2. In 50% of cases there were associated anomalies: distal
      bronchiectasis, bronchogenic cyst, anomaly of branching of bronchial tree and
      vascular structure. CONCLUSIONS: CBA is a relatively rare, generally
      oligosymptomatic malformation. Knowledge of the signs present at chest X-ray can
      prompt the radiologist to perform a CT scan. MDCT with multiplanar reconstruction
      is fundamental for the characterisation, localisation and study of the
      distribution of the lesion, helping to make a precise diagnosis. Surgery is
      seldom required and at any rate only performed in case of complications.

PMID- 16437041
TI  - CT findings in primary pulmonary lymphomas.
AB  - PURPOSE: To describe the CT findings of pathologically confirmed primary
      pulmonary lymphomas. MATERIALS AND METHODS: The CT examinations of 11 patients
      with pathologically proven primary pulmonary lymphoma (9 BALT lymphomas and 2 non
      BALT lymphomas) were retrospectively reviewed by three radiologists. Evaluated
      findings included morphology (consolidation, mass, nodule), number and
      distribution of lesions. Other CT findings such as air bronchogram,
      lymphadenopathy, atelectasis and pleural effusion were also assessed. RESULTS:
      Pulmonary lesions were depicted as airspace consolidation (pneumonia-like) in 5
      patients (45%), tumour-like rounded opacity in 4 (36%), and nodules in 4 (36%).
      Multiple and bilateral lung lesions were seen in 3 patients (27%). Air
      bronchogram was present in 7 patients (63%), lymphadenopathy in 3 (27%),
      atelectasis in 4 (36%) and pleural effusion in only 1 (9%). CONCLUSIONS: Our
      results agree with previous studies regarding lesion patterns and their relative
      frequency. A smaller number of nodules and multiple lesions were found compared
      with some previous studies. The most frequent pattern was airspace consolidation.

PMID- 16437042
TI  - Digital chest radiography system with amorphous selenium flat-panel detectors:
      Qualitative and dosimetric comparison with a dedicated film-screen system.
AB  - PURPOSE: To compare the quality and radiation dose of a conventional film-screen
      system and a digital system with amorphous selenium detectors in the study of the
      chest, by verifying overall performance and exposure levels for the main chest
      structures in patients of different sizes. MATERIALS AND METHODS: An analogic
      system (Chest-Changer, Dupont, Day-light model 1000) and a digital system
      (Directray Rad 1000C, Hologic) were tested on a total of 1000 patients randomly
      assigned to one of two groups of 500 subjects. The patients were further
      subdivided according to BMI (Body Mass Index). Image quality was determined by
      two chest radiologists who evaluated eight anatomical structures. The entrance
      surface dose (skin-dose), calculated based on the exposure parameters, was taken
      as the patient dose. RESULTS: Mean dose delivered was very similar for both
      techniques in the PA view (0.28 mGy), but it was greater in the LL projections
      obtained with the digital system (1.20 mGy versus 0.83 mGy). The highest overall
      scores were assigned to 43% and 23.2% analogic radiograms and 64% and 70.2%
      digital radiograms, for the PA and LL projections respectively. The scores
      assigned to the various anatomical structures confirmed the better performance of
      the digital system in almost all of the regions considered. CONCLUSIONS: The mean
      quality of radiograms is definitely higher with the digital system, in particular
      in the LL projections, where the higher patient doses are counterbalanced by
      fewer repeated scans. The greater level of exposure in the digital system appears
      nonetheless tolerable on account of the greater informativeness and therefore
      diagnostic gain and also considering the possibilities for improving the system.

PMID- 16437043
TI  - Imaging of the male breast.
AB  - Very few studies have dealt with the male breast, in particular as compared with
      the female breast, no doubt as a result of the high incidence and mortality of
      breast cancer in women. However, in routine practice breast radiologists are
      often faced with male breast disorders, but often have difficulties because of
      the limited experience in this field. The purpose of this pictorial essay is to
      summarise the clinical, pathophysiological, radiological and ultrasonographic
      patterns of male breast disorders based on a review of personal cases (398 cases
      from 1993 to 2004), in an attempt to propose guidelines for a more consistent
      approach to this only apparently marginal branch of male pathology.

PMID- 16437044
TI  - Proliferative high-risk lesions of the breast: contribution and limits of US
      guided core biopsy.
AB  - PURPOSE: To retrospectively correlate high-risk proliferative breast lesions
      (radial scar, atypical lobular hyperplasia, lobular carcinoma in situ and
      papillary lesions) diagnosed on core biopsy with the definitive histopathological
      diagnosis obtained after surgical excision or with the follow-up, in order to
      assess the role of core biopsy in such lesions. To discuss the management of the
      patient after a core biopsy diagnosis of high-risk proliferative breast lesion.
      MATERIAL AND METHODS: We evaluated 74 out of 1776 core biopsies consecutively
      performed on 67 patients. The histopathologic findings were as follows: 11 radial
      scars (RS), 3 atypical lobular hyperplasias (ALH), 3 lobular carcinomas in situ
      (LCIS), 57 benign papillary lesions. All patients underwent bilateral
      mammography, whole-breast ultrasound with a linear-array broadband transducer,
      and core biopsy with a 14 Gauge needle and a mean number of samples of 5 (range 4
      7). Sixty-two of 67 patients, for a total of 69/74 lesions, underwent surgical
      biopsy despite benign histopathologic findings, mostly because of highly
      suspicious imaging for malignancy (BIRADS 4-5), whereas 5 patients refused
      surgery and have been followed up for a least 18 months and are still being
      followed up (2 with RS, 1 with ADH and 2 with papillary lesions). RESULTS: Among
      the core biopsied lesions with a diagnosis of RS (n = 11) pathology revealed one
      ductal carcinoma in situ (DCIS) (this case was characterized by granular
      microcalcifications on mammography and by a mass with irregular margins on
      ultrasound). Also in the group of ADH (n = 3) pathology revealed one DCIS (lesion
      not visible on mammography but depicted as a suspicious mass on US). In the group
      of LCIS (n = 3) pathologists found an invasive lobular carcinoma (ILC). Among the
      benign papillary lesions (n = 57) histopathologic analysis of the surgical
      specimen revealed 7 malignant lesions (4 papillary carcinomas and 3 DCIS), whose
      mammographic and ultrasound findings were indistinguishable from benign lesions.
      Altogether there were 10 false negative results (underestimation) out of 74 core
      biopsies with a diagnosis of high-risk proliferative breast lesions. CONCLUSION:
      The high rate of histological underestimation after core biopsy (10/74) (13.5%)
      demands a very careful management of patents with a core biopsy diagnosis of high
      risk proliferative breast lesions, especially in the case of RS, lobular
      neoplasia and papillary lesions. However, the high imaging suspicion for
      malignancy prompts surgery. It is possible to assume that, when there is a low
      imaging suspicion for malignancy, when enough tissue has been sampled for
      pathology and no atypia is found within the lesions, surgery is not mandatory but
      a very careful follow-up is recommended. We must underline that there is no
      agreement regarding the quantity of tissue to sample. Vacuum-assisted biopsy may
      lead to better results, although there is as yet no proof that it can actually
      replace surgery in this group of lesions, since it seems only to reduce but not
      abolish the histological underestimation.

PMID- 16437045
TI  - Correlation of multimodality imaging in Paget's disease of bone.
AB  - PURPOSE: The aim of this study is double: 1. to review the known and less known
      radiographic patterns of Paget's disease of bone, employing the most recent
      imaging techniques; 2. to propose a rationale algorithm for the diagnosis and
      management of the disease. considering its inconsistency and clinical
      variability. MATERIALS AND METHODS: Forty-eight patients with Paget's disease of
      bone (30 males and 18 females, aged 45 and 88 years, mean age 71) were examined
      in the period 1999-2003. The patients were classified into two groups:
      symptomatic and asymptomatic. The first group, comprising 32 patients with
      generic ''low back pain'' with or without sciatica, or ''coxarthritis'' underwent
      conventional radiography. In the second group (16 patients), bone disease was
      discovered in course of radiological and/or scintigraphic examinations performed
      for other conditions. Subsequently, all the patients completed the diagnostic
      algorithm, consisting of radiographs of the remaining skeletal areas and those
      segments with abnormal scintigraphic uptake. RESULTS: Monostotic Paget's disease
      was observed in 31 cases (64.6%), of whom 20 males (64.6%) and 11 females
      (35.4%), whereas polyostotic disease was found in 17 cases (35.4%), of whom 10
      males (58.8%) and 7 females (41.2%). The sites most frequently affected in the
      monostotic form were: pelvis, 13 cases (43.3%); femur, 5 cases (16.7%); lumbar
      spine, 5 cases (16.7%); humerus, 2 cases (6.7%); tibia, 2 cases (6.7%); dorsal
      spine, skull, radius, patella, 1 case respectively (3.3%). In the polyostotic
      disease (17 cases), the affected bones were predominantly the skull, vertebral
      spine and pelvis (see text for their variable association). Pathologic fractures
      of the femur were found in two males. Osteogenic sarcoma (histological diagnosis)
      developed in the proximal femur in a 81 year-old male. CONCLUSIONS: Paget's
      disease is asymptomatic in the majority of affected individuals, and may be
      discovered incidentally with diagnosis being made on routine radiographs obtained
      for other purposes. Sometimes the x-ray features are so typical that the
      diagnosis is straightforward. Bone scan should be the imaging technique of
      choice, because tracer uptake is directly related to degree of activity of
      disease, and it may advance any radiographic evidence. Vertebral involvement is
      better evaluated by CT. Both CT and MRI are recommended in spine complications
      (pathological fractures, radicular or cord compression syndromes, malignant
      degeneration).

PMID- 16437046
TI  - Standard sonography and arthrosonography in the study of rotator cuff tears.
AB  - PURPOSE: The aim of this study was to evaluate the sensitivity of
      ultrasonography, integrating standard ultrasound and arthrosonography after
      injecting a saline solution into the glenohumeral cavity in cases of suspected
      rotator cuff tears. MATERIALS AND METHODS: We prospectively examined 40 patients
      awaiting shoulder arthroscopy for suspected or diagnosed tears of the rotator
      cuff. A radiologist, unaware of the pre-operative diagnosis, performed an
      ultrasound scan on all the patients before and after the injection of saline
      solution into the glenohumeral cavity. The parameters considered were presence or
      absence of a rotator cuff injury; type of injury according to Snyder and its
      extent along the longitudinal and transverse planes; presence or absence of
      effusion into the articular cavity; subacromial/subdeltoid bursal distension. All
      the patients underwent arthroscopy either the same day or the day after the
      ultrasound examination. RESULTS: Standard sonography showed 26 complete rotator
      cuff tears (type C according to Snyder), 2 partial tears (type B according to
      Snyder) and 12 intact rotator cuffs. Arthrosonography detected 31 complete
      rotator cuff tears (type C according to Snyder), 1 partial tear (type B according
      to Snyder) and 8 intact rotator cuffs.Arthroscopy identified 32 complete rotator
      cuff tears (type C according to Snyder), 1 partial tear (type B according to
      Snyder) and 8 intact rotator cuffs. Analysis of the results shows that, taking
      arthroscopy as the gold standard, the sensitivity of normal sonography is 81.2%,
      whereas that of arthrosonography is 96.8% (p < 0.05). CONCLUSIONS: On the basis
      of the data obtained in this study, standard sonography, integrated with the
      injection of a saline solution into the glenohumeral cavity, considerably
      increases the diagnostic sensitivity for rotator cuff tears. The authors suggest
      that arthrosonography can be used in the event of suspected rotator cuff tears,
      when MRI is contraindicated.

PMID- 16437047
TI  - High resolution ultrasonography in the diagnosis of the carpal tunnel syndrome.
AB  - PURPOSE: Carpal tunnel syndrome (CTS) is a neuropathy caused by compression of
      the median nerve in the carpal tunnel. Our purpose was to evaluate the role of
      high-resolution ultrasonography (US), performed with a 10-13 MHz probe, in the
      detection of morphovolumetric changes of the median nerve to confirm the clinical
      diagnosis. MATERIALS AND METHODS: Fifty healthy volunteers were examined first by
      US; subsequently we studied 294 wrists in 186 symptomatic patients, calculating
      the cross-sectional area of the median nerve at three levels: before the median
      nerve enters the carpal tunnel, at the carpal tunnel inlet and at the outlet. US
      was considered diagnostic for CTS when the median nerve area increased at the
      inlet or flattening was present along the carpal tunnel. RESULTS: Ultrasonography
      showed pathologic findings in 267 wrists: in 261 cases morphovolumetric changes
      of the median nerve were found; in six cases anatomic variant of the median nerve
      was detected. Surgery was performed in 277 cases and all patients became symptom
      free. The sensitivity of US was 96.3 % . CONCLUSIONS: Our study confirms that
      quantitative ultrasonographic assessment is a useful support in confirming the
      clinical diagnosis of CTS.

PMID- 16437048
TI  - Inferomedial displacement of the meniscal free fragment: MR findings.
AB  - PURPOSE: To define the accuracy of Magnetic Resonance (MR) in the diagnosis of
      inferomedial displacement of the meniscal fragment. MATERIALS AND METHODS: The MR
      examinations of the knee performed between December 2002 and April 2004 on 676
      patients (mean age 32 years) with knee trauma and subsequently subjected to
      arthroscopy were retrospectively reviewed to assess the presence of bucket-handle
      meniscal tear and inferomedial displacement of the meniscal free fragment. The MR
      examinations were performed using a superconductive 0.5 T MR unit with a
      transmitting/receiving coil dedicated for the extremities. The MR images were
      acquired with SE T1 and GE T2* sequences in the sagittal, coronal and axial
      planes with 3 mm thickness and 1 mm gap. The images were independently reviewed
      by two authors blinded to the arthroscopic findings. In case of disagreement, a
      third author, unaware of the arthroscopic findings, gave his judgment. RESULTS:
      On MR images a bucket-handle meniscal tear was identified in 54/676 patients. In
      6 out of 54 patients, an inferomedial meniscal fragment displacement of the
      medial meniscus with associated inflammatory synovial reaction around the
      fragment was detected. In one case an associated inflammatory bursal reaction
      with effusion around the distal insertion of the medial homolateral collateral
      ligament was detected. All cases were confirmed by arthroscopy and no statistical
      differences between the two authors were observed. CONCLUSIONS: MR allows the
      detection of the inferomedial meniscal fragment displacement and a more correct
      planning of arthroscopy with a strong reduction of repeat interventions.

PMID- 16437049
TI  - MRI in the acute phase of spinal cord traumatic lesions: Relationship between MRI
      findings and neurological outcome.
AB  - PURPOSE: To evaluate the role of emergency MRI in the diagnosis of acute spinal
      injuries, and to correlate the MRI pattern with the neurological outcome.
      MATERIALS AND METHODS: Thirty-eight patients with MRI-proven spinal cord injury
      were classified according to the Frankel classification. MRI was always performed
      within 8 hours from trauma. Frankel classification divides spinal cord injuries
      into 5 classes of decreasing severity based on the presence of motor and/or
      sensory function loss. On the basis of the MRI findings the patients were
      classified in 3 groups: group 1 (intramedullary haematoma), group 2 (multi
      metamer oedema), group 3 (single-metamer oedema). All patients underwent
      neurosurgery and were clinically evaluated until the stabilization of
      neurological recovery. Mean follow-up time was 12 months. The MR images were
      retrospectively evaluated and correlated to the neurological outcome. RESULTS:
      Twenty-eight patients showed complete motor loss (Frankel classes A and B); of
      these 28 patients 12 (42.8%) had MRI evidence of intramedullary haematoma, 12
      (42.8%) had multi-metamer oedema and 4 (14.4%) had single-metamer oedema. Of the
      10 patients with incomplete motor loss, none had MRI evidence of haemorrhage, 4
      (40%) showed multi-metamer oedema and 6 (60%) showed single-metamer oedema.
      Follow-up clinical assessment revealed that 14/38 patients (36,8%) had clinical
      improvement and 2/38 cases (5%) had a complete motor recovery, as demonstrated by
      the move to a higher Frankel class. CONCLUSIONS: Our results, consistent with
      previous reports, confirm a strong correlation between the MRI appearance of
      traumatic spinal cord injuries in acute phase and long-term recovery of motor and
      sensory function: patients with initial haemorrhage had a poor prognosis, whereas
      those with spinal cord oedema had a good clinical outcome, as demonstrated by the
      passage to a higher Frankel class. MRI is particularly important in the initial
      evaluation of unconscious patients who cannot undergo a motor and sensory
      neurological evaluation, and to define the prognosis, which will influence the
      correct therapeutic choice.

PMID- 16437050
TI  - Usefulness and limits of ultrasound-guided hook-wire positioning for localisation
      of soft tissue lesions prior to surgery.
AB  - PURPOSE: The aim of our study was to assess the usefulness of positioning metal
      wires under ultrasound guidance for localising soft tissue lesions in the
      preoperative phase. MATERIALS AND METHODS: We studied superficial soft-tissue
      lesions in 12 patients, using hooked mammographic wires of different lengths. One
      patient had a multifocal growth of disease which required a double localisation
      procedure. Correct positioning of the wire was confirmed by ultrasonography. All
      patients underwent surgery within five hours of hook-wire positioning. RESULTS:
      Correct wire position was confirmed at surgery in 12 out of 13 procedures. In one
      case the hook-wire reached the margin of the lesion. In all cases, the
      preoperative localisation procedure facilitated identification and resection of
      the masses. CONCLUSIONS: In our experience, the main indications for hook-wire
      positioning before surgery are: marking of small lesions, localisation of lesions
      in anatomic areas structurally subverted by previous surgery and consequently
      difficult to detect, guidance for surgical sectioning in order safeguard the
      noble structures close to the lesions.

PMID- 16437051
TI  - Pulled elbow in infancy: Diagnostic role of imaging.
AB  - PURPOSE: Pulled elbow is a common injury in infancy. Typically the child, after a
      sudden pull, refuses to use the arm. The history and clinical findings are
      sufficient to make the diagnosis, and radiography or ultrasonography are not
      necessary. When imaging procedures are performed, a few small signs are useful to
      confirm the diagnosis of pulled elbow. MATERIALS AND METHODS: The authors
      reviewed the radiographic and ultrasonographic signs reported to be suggestive of
      pulled elbow (increased radio-condylar distance, increased radio-coronoid
      distance, proximal radio-ulnar diastasis, deviation of the radio-condylar line)
      and attempted to confirm their presence in children affected by this trauma.
      RESULTS: Increased radio-condylar and radio-coronoid distance were present in 8
      of 8 cases; proximal radio-ulnar diastasis and deviation of the radio-condylar
      line were inconsistently present. Ultrasonography gave contradictory results:
      CONCLUSIONS: In typical cases of pulled elbow, radiography or ultrasonography are
      not necessary for diagnosis and treatment. Imaging procedures are recommended
      only in the case of non typical history, in the presence of deformity or
      traumatic skin lesions and in children over six years of age. Increased radio
      coronoid distance on the affected side is the most frequent and visible sign,
      which can confirm the diagnosis of pulled elbow. Increased radio-condylar
      distance is also present, but it is not easy to visualize. Proximal radio-ulnar
      diastasis and deviation of the radio-condylar line are inconstant.
      Ultrasonography is difficult to standardize.

PMID- 16437052
TI  - Usefulness of computed tomography in pre-surgical evaluation of maxillo-facial
      pathology with rapid prototyping and surgical pre-planning by virtual reality.
AB  - PURPOSE: To validate a protocol for creating virtual models to be used in the
      construction of solid prototypes useful for the planning-simulation of maxillo
      facial surgery, in particular for very complex anatomic and pathologic problems.
      To optimize communications between the radiology, engineering and surgical
      laboratories. METHODS AND MATERIALS: We studied 16 patients with different
      clinical problems of the maxillo-facial district. Exams were performed with
      multidetector computed tomography (MDCT) and single slice computed tomography
      (SDCT) with axial scans and collimation of 0.5-2 mm, and reconstruction interval
      of 1 mm. Subsequently we performed 2D multiplanar reconstructions and 3D volume
      rendering reconstructions. We exported the DICOM images to the engineering
      laboratory, to recognize and isolate the bony structures by software. With these
      data the solid prototypes were generated using stereolitography. To date, surgery
      has been preformed on 12 patients after simulation of the procedure on the
      stereolithographyc model. RESULTS: The solid prototypes constructed in the
      difficult cases were sufficiently detailed despite problems related to the
      artefacts generated by dental fillings an d prostheses. In the remaining cases
      the MPR/3D images were sufficiently detailed for surgical planning. The surgical
      results were excellent in all patients who underwent surgery, and the surgeons
      were satisfied with the improvement in quality and the reduction in time required
      for the procedure. CONCLUSIONS: MDCT enables rapid prototyping using solid
      replication, which was very helpful in maxillo-facial surgery, despite problems
      related to artifacts due to dental fillings and prosthesis within the acquisition
      field; solutions for this problem are work in progress. The protocol used for
      communication between the different laboratories was valid and reproducible.

PMID- 16437053
TI  - Acceptance testing of Computed Radiography systems.
AB  - Acceptance testing of computed radiography systems (CR) is required to verify not
      only image quality but also compliance with the manufacturer's specifications.
      Therefore, CR acceptance testing is manufacturer-specific. This paper describes a
      series of performance tests performed on a large number of CRs (FCR 5000, Fuji)
      recently acquired by our institution. In particular we describe the following
      tests: dark noise, uniformity, exposure calibration, linearity and autoranging,
      limiting resolution, noise and low-contrast resolution, spatial accuracy, laser
      beam function, erasure thoroughness, aliasing, grid response. Special attention
      is given to the practical aspects related to measurement and subsequent image
      analysis. We report the results obtained in the various tests. No significant
      variations from the reference levels were found. Nonetheless, in some cases the
      operating procedures had to be adapted.

PMID- 16437054
TI  - Method of patient dose evaluation in the angiographic and interventional
      radiology procedures.
AB  - PURPOSE: The aim of this study was to evaluate the effective dose in
      interventional radiology and angiography procedures on the basis of the dose-area
      product (DAP), either measured or calculated using two different methods.
      MATERIALS AND METHODS: We studied 2072 examinations carried out on several X-ray
      systems both in angiography and in interventional radiology. Some of the systems
      were equipped with an on-board transmission chamber for DAP measurements; for
      these systems we took direct DAP measurements for each type of examination. For
      the systems without the dose measurement device, we used a portable transmission
      chamber, acquiring the data from a set of sampling frames. We then derived the
      dose values from the systems' dosimetry data and the information about each
      examination. To this end, the dosimetry of each x-ray system was done by
      measuring tube output in the different acquisition modes, backscatter factor and
      field-homogeneity factor. Survey data sheets were filled in after every
      examination indicating the exposure data (mean Kv, mAs, focus-skin distance and
      field size). These values combined with the dosimetric data were used to evaluate
      the DAP for each exam. Where possible, we compared the measured and calculated
      DAP values by assessing the percentage deviation between each pair of values. A
      similar comparison was made for the single examinations using a simplified
      calculation algorithm reported in the literature. For all the examinations for
      which we had adequate survey data sheets, we estimated the DAP and the entrance
      dose values and, with the aid of WinODS software, the effective dose. RESULTS:
      The direct measurements of DAP showed that, in interventional radiology and
      angiographic procedures, the variability in examination conditions leads to a
      wide range of possible patient doses even within the same examination type. The
      comparison between the measured and calculated DAP using our algorithm showed
      substantial agreement (mean difference 30%, maximum 80%). By contrast, using the
      algorithm proposed in the literature, we obtained deviations higher than 100%. An
      estimate of the effective dose for all the recorded examinations (2072) permitted
      evaluation of both magnitude and variability of patient doses in special
      radiology procedures such as angiography and interventional radiology. However,
      it should be noted that evaluations based on calculated DAP values may be as
      uncertain as those estimated for DAP, and that clearly the evaluations made for
      the examinations for which direct measurements are available are more accurate.
      In particularly ''invasive'' examinations in terms of entrance dose, where the
      threshold limits for deterministic effects might possibly be exceeded, the
      equivalent doses to critical organs were also assessed. This analysis showed that
      in a small percentage of patients (5%) 2 Gy to the skin was exceeded in the areas
      exposed with possible transient erythema, while in fewer than 2% of patients, the
      3 Gy limit for temporary epilation was exceeded. CONCLUSIONS: Many interventional
      radiology, especially haemodynamic, examinations have shown to give significant
      exposure to patients. The direct dose measurement method has shown to be the only
      method able to provide reliable information on such exposure.However, the authors
      believe that since the patient dose cannot be established in advance, even in
      terms of magnitude and since direct dose measurement cannot be performed on all
      patients, it is nonetheless interesting to be able to assess, at least
      semiqualitatively, the amount of the above doses.

PMID- 16437055
TI  - Orf virus infection in humans--New York, Illinois, California, and Tennessee,
      2004-2005.
AB  - Orf virus is a zoonotic parapoxvirus endemic to most countries in the world and
      is principally associated with small ruminants (e.g., sheep and goats). Human orf
      infections appear as ulcerative skin lesions after contact with an infected
      animal or contaminated fomite. This report summarizes the epidemiologic and
      laboratory investigations of four sporadic cases of human orf infection,
      emphasizing the temporal association between human lesions and skin trauma or
      recent flock vaccination with live orf vaccine. This zoonotic infection shares
      clinical manifestations and exposure risks with other, potentially life
      threatening zoonoses (e.g., cutaneous anthrax) and is likely under-recognized
      because of a lack of clinical suspicion and widely available diagnostics. Barrier
      precautions and proper hand hygiene are recommended for the prevention of orf
      virus infection in humans.

PMID- 16437056
TI  - Rates of cesarean delivery among Puerto Rican women--Puerto Rico and the U.S.
      mainland, 1992-2002.
AB  - Cesarean delivery has been associated with greater risks for maternal morbidity,
      longer hospital stays, and rehospitalization after childbirth than vaginal
      delivery. On the U.S. mainland (i.e., 50 states and District of Columbia), rates
      of total cesarean delivery and primary cesarean delivery (i.e., for women without
      a previous cesarean) per 100 live births decreased from 1992 to 1996 before
      increasing from 1996 to 2002. During 2002, among all U.S. mainland births
      (approximately 4 million), 26% were by cesarean delivery; among all mainland
      births to women without a previous cesarean delivery, 18% were by primary
      cesarean. Cesarean delivery rates for Puerto Rican women who delivered on the
      U.S. mainland were similar to those for all women on the mainland. By contrast,
      among all 52,747 births in Puerto Rico in 2002, 45% were by cesarean delivery;
      among births in Puerto Rico to women without a previous cesarean delivery, 33%
      were primary cesarean deliveries. In addition, during 1996-2002, annual rates of
      vaginal births after cesarean delivery (VBAC) (i.e., per 100 live births to women
      who had a previous cesarean delivery) were lower in Puerto Rico than on the U.S.
      mainland. To compare trends in cesarean delivery during 1992-2002 among Puerto
      Rican women who delivered in Puerto Rico and on the U.S. mainland, CDC and the
      Puerto Rico Department of Health analyzed birth certificate data from the
      National Vital Statistics System (NVSS). This report summarizes the results of
      that analysis, which determined that, during 1992-2002, total and primary
      cesarean rates were consistently higher in Puerto Rico than among Puerto Rican
      women on the mainland. From 1996 to 2002, total and primary cesarean rates
      increased for Puerto Rican women in both places of delivery, but rates increased
      more sharply for women in Puerto Rico than on the mainland. The results suggest
      that measures to reduce the number of cesarean deliveries in Puerto Rico should
      focus on lowering the rate of primary cesarean deliveries, especially among women
      at low risk for a cesarean delivery.

PMID- 16437057
TI  - Surveillance for early detection of disease outbreaks at an outdoor mass
      gathering--Virginia, 2005.
AB  - Implementing public health surveillance at mass gatherings might help detect
      outbreaks or possible acts of biologic terrorism and enable prompt public health
      intervention. In July 2005, a daily syndromic sentinel surveillance system was
      implemented to monitor disease and injury among approximately 43,000 youths and
      adults attending a 10-day camping event held every 4 years by a national youth
      organization. Camp activities began on July 25, 2005, and included events such as
      mountain boarding, rappelling, and whittling. This report describes public health
      surveillance and response activities during the 10-day event and presents
      recommendations for health surveillance at large outdoor events. Public health
      surveillance should be implemented at mass gatherings to facilitate rapid
      detection of outbreaks and other health-related events and enable public health
      teams to respond with timely control measures.

PMID- 16437058
TI  - Prevalence of four developmental disabilities among children aged 8 years-
      Metropolitan Atlanta Developmental Disabilities Surveillance Program, 1996 and
      2000.
AB  - PROBLEM/CONDITION: In the United States, developmental disabilities affect
      approximately 17% of children aged <18 years, resulting in substantial financial
      and social costs. REPORTING PERIOD: 1996 and 2000. DESCRIPTION OF SYSTEM: The
      Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP)
      monitors the occurrence of mental retardation, cerebral palsy, hearing loss,
      vision impairment, and autism spectrum disorders among children aged 8 years in
      the five-county metropolitan Atlanta area (Clayton, Cobb, DeKalb, Fulton, and
      Gwinnett). MADDSP uses a multiple source ascertainment methodology. RESULTS:
      During 1996, the prevalence of mental retardation was 15.5 per 1,000 children
      aged 8 years; it decreased to 12.0 per 1,000 in 2000. The overall prevalence of
      cerebral palsy was 3.6 per 1,000 in 1996 and 3.1 per 1,000 in 2000. The
      prevalence of mental retardation and cerebral palsy was highest among males and
      black children. The prevalence of hearing loss was 1.4 per 1,000 in 1996 and 1.2
      per 1,000 in 2000; the prevalence of vision impairment during 1996 was 1.4 per
      1,000 and 1.2 per 1,000 in 2000. Minimal differences by study year were observed
      in the prevalence of all four disabilities when examined by sex, race, and
      severity. INTERPRETATION: The prevalence of these four select developmental
      disabilities in MADDSP was higher in 1996 than the annual average prevalence
      estimates for these disabilities during previous MADDSP study years (1991-1994)
      study years; the highest increase was observed among children with mental
      retardation. However, prevalence estimates during 2000 were more consistent with
      the estimates from the early 1990s. Data from additional surveillance years (2002
      and beyond) are needed to determine if the prevalence for 1996 was an anomaly and
      to continue to monitor trends in the prevalence of developmental disabilities
      over time. PUBLIC HEALTH ACTIONS: MADDSP data will continue to be used to examine
      trends in the occurrence of these disabilities over time, facilitate the
      development and implementation of appropriate intervention programs, and provide
      a framework for conducting population-based etiologic studies.

PMID- 16437059
TI  - Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane
      proteins in proximal tubule cells.
AB  - Tubulointerstitial nephritis is a cardinal renal manifestation in leptospirosis
      and LipL32, the major lipoprotein component of leptospiral outer membrane
      proteins (OMPs), induces a robust inflammatory response in cultured renal
      proximal tubule cells through a nuclear factor-kappaB-related pathway. Here, we
      investigated whether Toll-like receptor (TLR), known to play a pivotal role in
      innate immunity, could mediate the inflammatory response induced by leptospiral
      OMPs in renal proximal tubule cells. TLR expression was analyzed by flow
      cytometry and indirect immunofluorescence in cultured mouse proximal tubule
      (pyruvate kinase simian virus 40-proximal straight (PKSV-PR)) cells. Reverse
      transcription-competitive polymerase chain reaction and enzyme-linked
      immunosorbent assay were undertaken to analyze the inducible effects of inducible
      nitric oxide synthase (iNOS) and monocyte chemoattractant protein-1 (MCP-1 also
      termed CCL2) by pathogenic and non-pathogenic leptospiral OMPs and recombinant
      lipoproteins in either PKSV-PR cells or TLR-transfected human embryonic kidney
      (HEK) 293 cells. Anti-TLR antibodies were used for blocking experiments.
      Leptospira santarosai serovar Shermani OMPs and LipL32 induced a significant
      increase in TLR2 but not TLR4 expression in PKSV-PR cells. The increase in iNOS
      and CCL2/MCP-1 mRNA expressions could be prevented by an anti-TLR2 antibody, but
      not by an anti-TLR4 antibody. Furthermore, leptospiral OMPs stimulated both
      CCL2/MCP-1 mRNA and secreted protein in transfected HEK 293 cells with a TLR2
      expressing plasmid, but had no effect in cells with a TLR4-expressing plasmid. In
      conclusion, these findings indicate that the stimulation of iNOS and CCL2/MCP-1
      caused by pathogenic leptospiral OMPs, in particular LipL32, in proximal tubule
      cells requires TLR2 for the early inflammatory response.

PMID- 16437060
TI  - Estrogens and experimental ischemic stroke: a systematic review.
AB  - Estrogens are believed to provide females with endogenous protection against
      cerebrovascular events although clinical trials studying long-term hormone
      replacement have yielded disappointing results. In contrast, estrogens might be
      neuroprotective after experimental ischemia. We performed a systematic review of
      controlled experimental studies that administered estrogens before, or after,
      cerebral ischemia and measured lesion volume. Relevant studies were found from
      searching PubMed, Embase and Web of Science. From 161 identified publications, 27
      studies using 1,304 experimental subjects were analyzed using the Cochrane Review
      Manager software. Estrogens reduced lesion volume in a dose-dependent manner,
      after either transient (P<0.001) or permanent (P<0.001) ischemia and whether
      administered before or up to 4 h after ischemia onset; no studies assessed
      efficacy for later time periods. The effect size for estrogens decreased with
      increasing quality scores for studies of transient ischemia. Estrogens reduced
      lesion volume when administered to ovariectomized females and young adult males,
      but had no effect in intact females. Limited data were present for aged animals
      and the full dose-response relationship was not available in all experimental
      groups. On the basis of these data, estrogens are a candidate treatment for
      ischemic stroke, although further preclinical studies are also warranted.

PMID- 16437061
TI  - Epilepsy: a review of selected clinical syndromes and advances in basic science.
AB  - Epilepsy is a common neurologic disorder that manifests in diverse ways. There
      are numerous seizure types and numerous mechanisms by which the brain generates
      seizures. The two hallmarks of seizure generation are hyperexcitability of
      neurons and hypersynchrony of neural circuits. A large variety of mechanisms
      alters the balance between excitation and inhibition to predispose a local or
      widespread region of the brain to hyperexcitability and hypersynchrony. This
      review discusses five clinical syndromes that have seizures as a prominent
      manifestation. These five syndromes differ markedly in their etiologies and
      clinical features, and were selected for discussion because the seizures are
      generated at a different 'level' of neural dysfunction in each case: (1) mutation
      of a specific family of ion (potassium) channels in benign familial neonatal
      convulsions; (2) deficiency of the protein that transports glucose into the CNS
      in Glut-1 deficiency; (3) aberrantly formed local neural circuits in focal
      cortical dysplasia; (4) synaptic reorganization of limbic circuitry in temporal
      lobe epilepsy; and (5) abnormal thalamocortical circuit function in childhood
      absence epilepsy. Despite this diversity of clinical phenotype and mechanism,
      these syndromes are informative as to how pathophysiological processes converge
      to produce brain hyperexcitability and seizures.

PMID- 16437063
TI  - Earth science: a wet mantle conductor?
AB  - The suggestion that the transition zone of Earth's mantle (410-670 km in depth)
      is enriched in water is of great possible significance to the geodynamics and
      geochemistry of Earth's interior, as well as for the role of the mantle in the
      global water cycle. Huang et al. compare the effect of water on electrical
      conductivities of transition-zone phases to electromagnetic and magnetotelluric
      soundings of the mantle beneath the North Pacific and conclude that the
      transition zone contains between 1,000 and 2,000 p.p.m. of water, which is
      considerably more than the 50-200 p.p.m. present in the upper mantle. This
      conclusion is predicated on the assumption that the transition zone is relatively
      oxidized, but in fact fairly reduced conditions are more likely. Here I show that
      if the transition zone is reduced, high conductivities can be explained without
      the requirement for large enrichments of water.

PMID- 16437066
TI  - A firm foundation?

PMID- 16437067
TI  - Chinese hesitancy on avian flu.

PMID- 16437068
TI  - Warming to economics.

PMID- 16437070
TI  - The costs of global warming.

PMID- 16437072
TI  - Nations wrestle to host future telescope.

PMID- 16437071
TI  - Panel quits in row over sonar damage.

PMID- 16437073
TI  - A brief history of Pluto.

PMID- 16437074
TI  - Treasure island: pinning down a model ecosystem.

PMID- 16437075
TI  - Bad data fail to halt patents.

PMID- 16437076
TI  - India's ban on foreign boats hinders tsunami research.

PMID- 16437080
TI  - China: open season.

PMID- 16437081
TI  - Genomics: discovery in the dirt.

PMID- 16437082
TI  - Literary Darwinism: textual selection.

PMID- 16437083
TI  - The right combination.

PMID- 16437086
TI  - Don't forget randomness is still just a hypothesis.

PMID- 16437087
TI  - Branding can be justified in vital conservation research.

PMID- 16437088
TI  - No clear evidence to disprove optics thesis.

PMID- 16437089
TI  - Biodiversity data are out of local taxonomists' reach.

PMID- 16437094
TI  - A better than perfect match.

PMID- 16437095
TI  - Physiology: plants on a different scale.

PMID- 16437096
TI  - Extrasolar planets: light through a gravitational lens.

PMID- 16437097
TI  - Travel: fitting the bill.

PMID- 16437098
TI  - Metabolism: bile acids heat things up.

PMID- 16437101
TI  - Materials science: a new order for metallic glasses.

PMID- 16437100
TI  - Development: twists of fate in the brain.

PMID- 16437102
TI  - DNA repair: tails of histones lost.

PMID- 16437103
TI  - Biogeography: molecular trails from hitch-hiking snails.
AB  - Darwin was fascinated by the transportation of land snails across great swathes
      of open ocean by birds--he even immersed snails in sea water to see how long they
      would survive. Here we follow a molecular phylogenetic trail that reveals the
      incredible transequatorial dispersal of the land snail Balea from Europe to the
      Azores and the Tristan da Cunha islands, and back again. This long-distance
      dispersal is unexpected for what are proverbially considered the most pedestrian
      of creatures.

PMID- 16437104
TI  - The search for a topographic signature of life.
AB  - Landscapes are shaped by the uplift, deformation and breakdown of bedrock and the
      erosion, transport and deposition of sediment. Life is important in all of these
      processes. Over short timescales, the impact of life is quite apparent: rock
      weathering, soil formation and erosion, slope stability and river dynamics are
      directly influenced by biotic processes that mediate chemical reactions, dilate
      soil, disrupt the ground surface and add strength with a weave of roots. Over
      geologic time, biotic effects are less obvious but equally important: biota
      affect climate, and climatic conditions dictate the mechanisms and rates of
      erosion that control topographic evolution. Apart from the obvious influence of
      humans, does the resulting landscape bear an unmistakable stamp of life? The
      influence of life on topography is a topic that has remained largely unexplored.
      Erosion laws that explicitly include biotic effects are needed to explore how
      intrinsically small-scale biotic processes can influence the form of entire
      landscapes, and to determine whether these processes create a distinctive
      topography.

PMID- 16437105
TI  - Atomic packing and short-to-medium-range order in metallic glasses.
AB  - Unlike the well-defined long-range order that characterizes crystalline metals,
      the atomic arrangements in amorphous alloys remain mysterious at present. Despite
      intense research activity on metallic glasses and relentless pursuit of their
      structural description, the details of how the atoms are packed in amorphous
      metals are generally far less understood than for the case of network-forming
      glasses. Here we use a combination of state-of-the-art experimental and
      computational techniques to resolve the atomic-level structure of amorphous
      alloys. By analysing a range of model binary systems that involve different
      chemistry and atomic size ratios, we elucidate the different types of short-range
      order as well as the nature of the medium-range order. Our findings provide a
      reality check for the atomic structural models proposed over the years, and have
      implications for understanding the nature, forming ability and properties of
      metallic glasses.

PMID- 16437106
TI  - Policing stabilizes construction of social niches in primates.
AB  - All organisms interact with their environment, and in doing so shape it,
      modifying resource availability. Termed niche construction, this process has been
      studied primarily at the ecological level with an emphasis on the consequences of
      construction across generations. We focus on the behavioural process of
      construction within a single generation, identifying the role a robustness
      mechanism--conflict management--has in promoting interactions that build social
      resource networks or social niches. Using 'knockout' experiments on a large,
      captive group of pigtailed macaques (Macaca nemestrina), we show that a policing
      function, performed infrequently by a small subset of individuals, significantly
      contributes to maintaining stable resource networks in the face of chronic
      perturbations that arise through conflict. When policing is absent, social niches
      destabilize, with group members building smaller, less diverse, and less
      integrated grooming, play, proximity and contact-sitting networks. Instability is
      quantified in terms of reduced mean degree, increased clustering, reduced reach,
      and increased assortativity. Policing not only controls conflict, we find it
      significantly influences the structure of networks that constitute essential
      social resources in gregarious primate societies. The structure of such networks
      plays a critical role in infant survivorship, emergence and spread of cooperative
      behaviour, social learning and cultural traditions.

PMID- 16437107
TI  - Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb
      silencing.
AB  - Cancer is both a genetic and an epigenetic disease. Inactivation of tumour
      suppressor genes by epigenetic changes is frequently observed in human cancers,
      particularly as a result of the modifications of histones and DNA methylation. It
      is therefore important to understand how these damaging changes might come about.
      By studying tumorigenesis in the Drosophila eye, here we identify two Polycomb
      group epigenetic silencers, Pipsqueak and Lola, that participate in this process.
      When coupled with overexpression of Delta, deregulation of the expression of
      Pipsqueak and Lola induces the formation of metastatic tumours. This phenotype
      depends on the histone-modifying enzymes Rpd3 (a histone deacetylase), Su(var)3-9
      and E(z), as well as on the chromodomain protein Polycomb. Expression of the gene
      Retinoblastoma-family protein (Rbf) is downregulated in these tumours and,
      indeed, this downregulation is associated with DNA hypermethylation. Together,
      these results establish a mechanism that links the Notch-Delta pathway,
      epigenetic silencing pathways and cell-cycle control in the process of
      tumorigenesis.

PMID- 16437108
TI  - Discovery of a cool planet of 5.5 Earth masses through gravitational
      microlensing.
AB  - In the favoured core-accretion model of formation of planetary systems, solid
      planetesimals accumulate to build up planetary cores, which then accrete nebular
      gas if they are sufficiently massive. Around M-dwarf stars (the most common stars
      in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune
      mass planets with orbital radii of 1 to 10 astronomical units (au), which is
      consistent with the small number of gas giant planets known to orbit M-dwarf host
      stars. More than 170 extrasolar planets have been discovered with a wide range of
      masses and orbital periods, but planets of Neptune's mass or less have not
      hitherto been detected at separations of more than 0.15 au from normal stars.
      Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a
      separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o)
      refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a
      planetary mass companion to the lens star of the microlensing event.) The mass is
      lower than that of GJ876d (ref. 5), although the error bars overlap. Our
      detection suggests that such cool, sub-Neptune-mass planets may be more common
      than gas giant planets, as predicted by the core accretion theory.

PMID- 16437109
TI  - Laser acceleration of quasi-monoenergetic MeV ion beams.
AB  - Acceleration of particles by intense laser-plasma interactions represents a
      rapidly evolving field of interest, as highlighted by the recent demonstration of
      laser-driven relativistic beams of monoenergetic electrons. Ultrahigh-intensity
      lasers can produce accelerating fields of 10 TV m(-1) (1 TV = 10(12) V),
      surpassing those in conventional accelerators by six orders of magnitude. Laser
      driven ions with energies of several MeV per nucleon have also been produced.
      Such ion beams exhibit unprecedented characteristics--short pulse lengths, high
      currents and low transverse emittance--but their exponential energy spectra have
      almost 100% energy spread. This large energy spread, which is a consequence of
      the experimental conditions used to date, remains the biggest impediment to the
      wider use of this technology. Here we report the production of quasi
      monoenergetic laser-driven C5+ ions with a vastly reduced energy spread of 17%.
      The ions have a mean energy of 3 MeV per nucleon (full-width at half-maximum
      approximately 0.5 MeV per nucleon) and a longitudinal emittance of less than 2 x
      10(-6) eV s for pulse durations shorter than 1 ps. Such laser-driven, high
      current, quasi-monoenergetic ion sources may enable significant advances in the
      development of compact MeV ion accelerators, new diagnostics, medical physics,
      inertial confinement fusion and fast ignition.

PMID- 16437110
TI  - Laser-plasma acceleration of quasi-monoenergetic protons from microstructured
      targets.
AB  - Particle acceleration based on high intensity laser systems (a process known as
      laser-plasma acceleration) has achieved high quality particle beams that compare
      favourably with conventional acceleration techniques in terms of emittance,
      brightness and pulse duration. A long-term difficulty associated with laser
      plasma acceleration--the very broad, exponential energy spectrum of the emitted
      particles--has been overcome recently for electron beams. Here we report
      analogous results for ions, specifically the production of quasi-monoenergetic
      proton beams using laser-plasma accelerators. Reliable and reproducible laser
      accelerated ion beams were achieved by intense laser irradiation of solid
      microstructured targets. This proof-of-principle experiment serves to illuminate
      the role of laser-generated plasmas as feasible particle sources. Scalability
      studies show that, owing to their compact size and reasonable cost, such table
      top laser systems with high repetition rates could contribute to the development
      of new generations of particle injectors that may be suitable for medical proton
      therapy.

PMID- 16437111
TI  - Amplification of chirality in two-dimensional enantiomorphous lattices.
AB  - The concept of chirality dates back to 1848, when Pasteur manually separated left
      handed from right-handed sodium ammonium tartrate crystals. Crystallization is
      still an important means for separating chiral molecules into their two different
      mirror-image isomers (enantiomers), yet remains poorly understood. For example,
      there are no firm rules to predict whether a particular pair of chiral partners
      will follow the behaviour of the vast majority of chiral molecules and
      crystallize together as racemic crystals, or as separate enantiomers. A somewhat
      simpler and more tractable version of this phenomenon is crystallization in two
      dimensions, such as the formation of surface structures by adsorbed molecules.
      The relatively simple spatial molecular arrangement of these systems makes it
      easier to study the effects of specific chiral interactions; moreover, chiral
      assembly and recognition processes can be observed directly and with molecular
      resolution using scanning tunnelling microscopy. The enantioseparation of chiral
      molecules in two dimensions is expected to occur more readily because planar
      confinement excludes some bulk crystal symmetry elements and enhances chiral
      interactions; however, many surface structures have been found to be racemic.
      Here we show that the chiral hydrocarbon heptahelicene on a Cu111 surface does
      not undergo two-dimensional spontaneous resolution into enantiomers, but still
      shows enantiomorphism on a mesoscopic length scale that is readily amplified.
      That is, we observe formation of racemic heptahelicene domains with non
      superimposable mirror-like lattice structures, with a small excess of one of the
      heptahelicene enantiomers suppressing the formation of one domain type. Similar
      to the induction of homochirality in achiral enantiomorphous monolayers by a
      chiral modifier, a small enantiomeric excess suffices to ensure that the entire
      molecular monolayer consists of domains having only one of two possible, non
      superimposable, mirror-like lattice structures.

PMID- 16437112
TI  - A climatologically significant aerosol longwave indirect effect in the Arctic.
AB  - The warming of Arctic climate and decreases in sea ice thickness and extent
      observed over recent decades are believed to result from increased direct
      greenhouse gas forcing, changes in atmospheric dynamics having anthropogenic
      origin, and important positive reinforcements including ice-albedo and cloud
      radiation feedbacks. The importance of cloud-radiation interactions is being
      investigated through advanced instrumentation deployed in the high Arctic since
      1997 (refs 7, 8). These studies have established that clouds, via the dominance
      of longwave radiation, exert a net warming on the Arctic climate system
      throughout most of the year, except briefly during the summer. The Arctic region
      also experiences significant periodic influxes of anthropogenic aerosols, which
      originate from the industrial regions in lower latitudes. Here we use multisensor
      radiometric data to show that enhanced aerosol concentrations alter the
      microphysical properties of Arctic clouds, in a process known as the 'first
      indirect' effect. Under frequently occurring cloud types we find that this leads
      to an increase of an average 3.4 watts per square metre in the surface longwave
      fluxes. This is comparable to a warming effect from established greenhouse gases
      and implies that the observed longwave enhancement is climatologically
      significant.

PMID- 16437113
TI  - Universal scaling of respiratory metabolism, size and nitrogen in plants.
AB  - The scaling of respiratory metabolism to body size in animals is considered to be
      a fundamental law of nature, and there is substantial evidence for an approximate
      (3/4)-power relation. Studies suggest that plant respiratory metabolism also
      scales as the (3/4)-power of mass, and that higher plant and animal scaling
      follow similar rules owing to the predominance of fractal-like transport networks
      and associated allometric scaling. Here, however, using data obtained from about
      500 laboratory and field-grown plants from 43 species and four experiments, we
      show that whole-plant respiration rate scales approximately isometrically
      (scaling exponent approximately 1) with total plant mass in individual
      experiments and has no common relation across all data. Moreover, consistent with
      theories about biochemically based physiological scaling, isometric scaling of
      whole-plant respiration rate to total nitrogen content is observed within and
      across all data sets, with a single relation common to all data. This isometric
      scaling is unaffected by growth conditions including variation in light, nitrogen
      availability, temperature and atmospheric CO2 concentration, and is similar
      within or among species or functional groups. These findings suggest that plants
      and animals follow different metabolic scaling relations, driven by distinct
      mechanisms.

PMID- 16437114
TI  - The scaling laws of human travel.
AB  - The dynamic spatial redistribution of individuals is a key driving force of
      various spatiotemporal phenomena on geographical scales. It can synchronize
      populations of interacting species, stabilize them, and diversify gene pools.
      Human travel, for example, is responsible for the geographical spread of human
      infectious disease. In the light of increasing international trade, intensified
      human mobility and the imminent threat of an influenza A epidemic, the knowledge
      of dynamical and statistical properties of human travel is of fundamental
      importance. Despite its crucial role, a quantitative assessment of these
      properties on geographical scales remains elusive, and the assumption that humans
      disperse diffusively still prevails in models. Here we report on a solid and
      quantitative assessment of human travelling statistics by analysing the
      circulation of bank notes in the United States. Using a comprehensive data set of
      over a million individual displacements, we find that dispersal is anomalous in
      two ways. First, the distribution of travelling distances decays as a power law,
      indicating that trajectories of bank notes are reminiscent of scale-free random
      walks known as Levy flights. Second, the probability of remaining in a small,
      spatially confined region for a time T is dominated by algebraically long tails
      that attenuate the superdiffusive spread. We show that human travelling behaviour
      can be described mathematically on many spatiotemporal scales by a two-parameter
      continuous-time random walk model to a surprising accuracy, and conclude that
      human travel on geographical scales is an ambivalent and effectively
      superdiffusive process.

PMID- 16437115
TI  - Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell
      movement.
AB  - Embryonic cell movement is essential for morphogenesis and the establishment of
      body shapes, but little is known about its mechanism. Here we report that
      pregnenolone, which is produced from cholesterol by the steroidogenic enzyme
      Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc), functions in promoting
      cell migration during epiboly. Epiboly is a process in which embryonic cells
      spread from the animal pole to cover the underlying yolk. During epiboly, cyp11a1
      is expressed in an extra-embryonic yolk syncytial layer. Reducing cyp11a1
      expression in zebrafish using antisense morpholino oligonucleotides did not
      perturb cell fates, but caused epibolic delay. This epibolic defect was partially
      rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone.
      We show that the epibolic delay is accompanied by a decrease in the level of
      polymerized microtubules, and that pregnenolone can rescue this microtubule
      defect. Our results indicate that pregnenolone preserves microtubule abundance
      and promotes cell movement during epiboly.

PMID- 16437116
TI  - Architecture of ribonucleoprotein complexes in influenza A virus particles.
AB  - In viruses, as in eukaryotes, elaborate mechanisms have evolved to protect the
      genome and to ensure its timely replication and reliable transmission to progeny.
      Influenza A viruses are enveloped, spherical or filamentous structures, ranging
      from 80 to 120 nm in diameter. Inside each envelope is a viral genome consisting
      of eight single-stranded negative-sense RNA segments of 890 to 2,341 nucleotides
      each. These segments are associated with nucleoprotein and three polymerase
      subunits, designated PA, PB1 and PB2; the resultant ribonucleoprotein complexes
      (RNPs) resemble a twisted rod (10-15 nm in width and 30-120 nm in length) that is
      folded back and coiled on itself. Late in viral infection, newly synthesized RNPs
      are transported from the nucleus to the plasma membrane, where they are
      incorporated into progeny virions capable of infecting other cells. Here we show,
      by transmission electron microscopy of serially sectioned virions, that the RNPs
      of influenza A virus are organized in a distinct pattern (seven segments of
      different lengths surrounding a central segment). The individual RNPs are
      suspended from the interior of the viral envelope at the distal end of the
      budding virion and are oriented perpendicular to the budding tip. This finding
      argues against random incorporation of RNPs into virions, supporting instead a
      model in which each segment contains specific incorporation signals that enable
      the RNPs to be recruited and packaged as a complete set. A selective mechanism of
      RNP incorporation into virions and the unique organization of the eight RNP
      segments may be crucial to maintaining the integrity of the viral genome during
      repeated cycles of replication.

PMID- 16437122
TI  - Variation in the type I interferon gene cluster on 9p21 influences susceptibility
      to asthma and atopy.
AB  - A genome-wide screen for asthma and atopy susceptibility alleles conducted in the
      Hutterites, a founder population of European descent, reported evidence of
      linkage with a short tandem repeat polymorphism (STRP) within the type I
      interferon (IFN) gene cluster on chromosome 9p21. The goal of this study was to
      identify variation within the IFN gene cluster that influences susceptibility to
      asthma and atopic phenotypes. We screened approximately 25 kb of sequence,
      including the flanking sequence of all 15 functional genes and the single coding
      exon in 12, in Hutterites representing different IFNA-STRP genotypes. We
      identified 78 polymorphisms, and genotyped 40 of these (in 14 genes) in a large
      Hutterite pedigree. Modest associations (0.003<P<0.05) with asthma, bronchial
      hyper-responsiveness (BHR), and atopy were observed with individual variants or
      genes, spanning the entire 400 kb region. However, pairwise combinations of
      haplotypes between genes showed highly significant associations with different
      phenotypes (P<10(-5)) that were localized to specific pairs of genes or regions
      of this cluster. These results suggest that variation in multiple genes in the
      type I IFN cluster on 9p22 contribute to asthma and atopy susceptibility, and
      that not all genes contribute equally to all phenotypes.

PMID- 16437123
TI  - Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms
      Asp299Gly and Thr399ile are hypo-responsive to Porphyromonas gingivalis.
AB  - The Toll-like receptor (TLR)4 is the major sensor for bacterial
      lipopolysaccharide and its two common co-segregating polymorphisms, Asp299Gly and
      Thr399Ile, which occur at a frequency of between 6 and 10%, have been associated
      with infectious diseases, LPS hypo-responsiveness and cardiovascular disease.
      Porphyromonas gingivalis is a Gram-negative bacterium implicated in chronic
      periodontitis and is a known TLR4 and TLR2 agonist. We obtained two gingival
      epithelial cell primary cultures from subjects heterozygous for the TLR4
      polymorphism Asp299Gly and compared response characteristics with similar cells
      from patients (four) with the wild-type TLR4 genes. Cytokine responses and
      transcriptome profiles of gingival epithelial cell primary culture cells to
      TNFalpha challenge were similar for all primary epithelial cell cultures. P.
      gingivalis challenge, however, gave markedly different responses for Asp299Gly
      heterozygous and wild-type epithelial cell cultures. The epithelial cells
      heterozygous for the TLR4 polymorphism Asp299Gly were functionally hypo
      responsive, evidenced by differences in BD-2 mRNA expression, mRNA response
      profile by microarray analysis and by pro-inflammatory and chemokine cytokines at
      the protein and mRNA level. These findings emphasize variance in human epithelial
      cell TLRs, linked with Asp299Gly carriage, which results in a hypo-responsive
      epithelial cell phenotype less susceptible to Gram-negative diseases and
      associated systemic conditions.

PMID- 16437124
TI  - The association between microsatellite polymorphisms in intron II of the human
      Toll-like receptor 2 gene and tuberculosis among Koreans.
AB  - The observation that Toll-like receptor (TLR)2-deficient mice are highly
      susceptible to mycobacteria suggests that mutations altering TLR2 expression may
      impair host response to Mycobacterium tuberculosis. We evaluated the association
      between guanine-thymine (GT) repeat polymorphism in intron II of the TLR2 gene
      and the presence of tuberculosis (TB) in Koreans. The numbers of GT repeats were
      determined by PCR and gene scans for 176 TB patients and 196 controls. The
      recombinant TLR2 promoter/exonI/exonII/intronII/luciferase constructs including
      three representative repeats: (GT)13, (GT)20, and (GT)24 were transfected into
      K562 cells, and luciferase activities were estimated and compared. The expression
      of TLR2 on CD14+ peripheral blood mononuclear cells (PBMC) from healthy
      volunteers were measured with flow cytometry. Genotypes with shorter GT repeats
      were more common among TB patients (49.4 vs 37.7%, P=0.02). This observation was
      confirmed among 82 other TB patients as a validation cohort. Shorter GT repeats
      were associated with weaker promoter activities and lower TLR2 expression on
      CD14+ PBMCs. In conclusion, the development of TB disease in Koreans was
      associated with shorter GT repeats in intron II of the TLR2 gene. This
      association is correlated with lower expression of TLR2 through weaker promoter
      activity for genes with shorter GT repeats.

PMID- 16437127
TI  - Mild hyperhomocysteinaemia is associated with increased aortic stiffness in
      general population.
AB  - Total homocysteine (tHcy) level was identified as a strong and independent
      predictor of cardiovascular events. We investigated the association between tHcy
      and mechanical properties of large arteries in a random, general population-based
      sample of 251 subjects (mean age 48 years). Large artery properties, such as
      aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation
      index of radial artery were measured using semi-automatic Sphygmocor device.
      Aortic PWV (APWV) positively correlated with tHcy (r = 0.28, P<0.0001), and a
      significant increasing trend of APWV was found by tHcy quartiles (P = 0.0003 by
      ANOVA). This association remained significant after adjustment for conventional
      cardiovascular risk factors (age, gender, smoking, overweight, hypertension,
      dyslipidaemia and impaired glucose metabolism) and for usual homocysteine
      confounders (folate, B12, renal function). Subjects with mild
      hyperhomocysteinaemia (i.e. with tHcy > or = 15 micromol/l) had 2.74 times higher
      risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such
      association was found either for PWV measured at lower extremity or for radial
      augmentation index. In conclusion, in our series of subjects from general
      population, we found a strong and independent relationship between homocysteine
      concentration and APWV, a parameter of stiffness of central arteries.

PMID- 16437128
TI  - White blood cell count and hypertension.

PMID- 16437129
TI  - Quantitative genetic analysis of blood pressure reactivity to orthostatic tilt
      using principal components analysis.
AB  - Blood pressure (BP) reactivity to orthostatic tilt may be predictive of
      cardiovascular disease. However, the genetic and environmental influences on BP
      reactivity to tilt have not been well examined. Identifying different influences
      on BP at rest and BP during tilt is complicated by the intercorrelation among
      multiple measurements. In this study, we use principal components analysis (PCA)
      to reduce multivariate BP data into components that are orthogonal. The objective
      of this study is to characterize and examine the genetic architecture of BP at
      rest and during head-up tilt (HUT). Specifically, we estimate the heritability of
      individual BP measures and three principal components (PC) derived from multiple
      BP measurements during HUT. Additionally, we estimate covariate effects on these
      traits. The study sample consisted of 444 individuals, distributed across four
      large families. HUT consisted of 70 degrees head-up table tilting while strapped
      to a tilt table. BP reactivity (deltaBP) was defined as BP during HUT minus BP
      while supine. Three PC extracted from the PCA were interpreted as 'general BP'
      (PC1), 'pulse pressure' (PC2) and 'BP reactivity' (PC3). Variance components
      methods were used to estimate the heritabilities of resting BP, HUT BP, deltaBP,
      as well as the three BP PC. Significant (P<0.05) heritabilities were found for
      all BP measurements, except for systolic deltaBP at 1 and 3 min, and diastolic
      deltaBP at 2 min. Significant genetic effects were also found for the three PC.
      Each of these orthogonal components is significantly influenced by somewhat
      different sets of covariates.

PMID- 16437130
TI  - Proliferating endothelial cell-specific expression of IGF-I receptor ribozyme
      inhibits retinal neovascularization.
AB  - Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for
      normal ocular development and are expressed in numerous ocular cell types
      including lens epithelial cells, retinal pigment epithelial cells, Muller cells
      and endothelial cells. Endothelial cell proliferation is a common feature of
      proliferative retinopathies and involves abnormal growth of blood vessels within
      and on the surface of the retina. In an effort to inhibit the formation of these
      aberrant blood vessels, we cloned an IGF-IR ribozyme into an expression vector
      that limits expression of the ribozyme to proliferating endothelial cells. An
      endothelin enhancer and Cdc6 promoter chimera drives expression of the IGF-IR
      ribozyme. This promoter limited retinal expression of the reporter gene to
      proliferating endothelial cells in two mouse models of proliferative retinopathy.
      In addition, expression of the IGF-IR ribozyme by this promoter inhibited
      aberrant retinal angiogenesis in both models while preserving normal vessels.
      These results demonstrate the feasibility of IGF-IR ribozyme expression in a
      selective manner for safer treatment of abnormal angiogenesis associated with
      retinopathy.

PMID- 16437131
TI  - Readministration of helper-dependent adenovirus to mouse lung.
AB  - Adenovirus vectors (Ad) are widely used in gene therapy studies, including those
      aimed at treating cystic fibrosis lung disease. Various approaches have been
      investigated to blunt the host immune response to Ad, including development of
      helper-dependent (HD) Ad. The host cytotoxic T-cell response to HD-Ad is
      generally lower than to earlier-generation Ad. However, antibodies are formed
      which could inhibit the efficacy of HD-Ad readministration. In this first study
      of HD-Ad readministration to the lung, we found that a second administration of
      HD-Ad to mice was possible with minimal loss of transgene expression. In
      contrast, when first-generation (FG) Ad was administered initially, followed by
      HD-Ad or FG-Ad, transgene expression was reduced. Significantly lower
      concentrations of antibodies against Ad were found in lung lavage fluid and serum
      from mice that received two doses of HD-Ad (when the initial HD-Ad lacked a
      transgene), compared to mice that received FG-Ad followed by HD-Ad. These data
      suggest that readministration of HD-Ad for lung gene therapy may be feasible.

PMID- 16437132
TI  - Cyclic stretch-induced reorganization of the cytoskeleton and its role in
      enhanced gene transfer.
AB  - Cyclic stretch is known to alter a number of cellular and subcellular processes,
      including those involved in nonviral gene delivery. We have previously shown that
      moderate equibiaxial cyclic stretch (10% change in basement membrane area, 0.5
      Hz, 50% duty cycle) of human pulmonary A549 cells enhances gene transfer and
      expression of reporter plasmid DNA in vitro, and that this phenomena may be due
      to alterations in cytoplasmic trafficking. Although the path by which plasmid DNA
      travels through the cytoplasm toward the nucleus is not well understood, the
      cytoskeleton and the constituents of the cytoplasm are known to significantly
      hinder macromolecular diffusion. Using biochemical techniques and
      immunofluorescence microscopy, we show that both the microfilament and
      microtubule networks are significantly reorganized by equibiaxial cyclic stretch.
      Prevention of this reorganization through the use of cytoskeletal stabilizing
      compounds mitigates the stretch-induced increase in gene expression, however,
      depolymerization in the absence of stretch is not sufficient to increase gene
      expression. These results suggest that cytoskeletal reorganization plays an
      important role in stretch-induced gene transfer and expression.

PMID- 16437133
TI  - Effective oligonucleotide-mediated gene disruption in ES cells lacking the
      mismatch repair protein MSH3.
AB  - We have previously demonstrated that site-specific insertion, deletion or
      substitution of one or two nucleotides in mouse embryonic stem cells (ES cells)
      by single-stranded deoxyribo-oligonucleotides is several hundred-fold suppressed
      by DNA mismatch repair (MMR) activity. Here, we have investigated whether
      compound mismatches and larger insertions escape detection by the MMR machinery
      and can be effectively introduced in MMR-proficient cells. We identified several
      compound mismatches that escaped detection by the MMR machinery to some extent,
      but could not define general rules predicting the efficacy of complex base-pair
      substitutions. In contrast, we found that four-nucleotide insertions were largely
      subject to suppression by the MSH2/MSH3 branch of MMR and could be effectively
      introduced in Msh3-deficient cells. As these cells have no overt mutator
      phenotype and Msh3-deficient mice do not develop cancer, Msh3-deficient ES cells
      can be used for oligonucleotide-mediated gene disruption. As an example, we
      present disruption of the Fanconi anemia gene Fancf.

PMID- 16437134
TI  - Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute
      leukemia identified by the EGIL scoring system.
AB  - Biphenotypic acute leukemia (BAL) is a rare, difficult to diagnose entity. Its
      identification is important for risk stratification in acute leukemia (AL). The
      scoring proposal of the European Group for the Classification of Acute Leukemia
      (EGIL) is useful for this purpose, but its performance against objective
      benchmarks is unclear. Using the EGIL system, we identified 23 (3.4%) BAL from
      among 676 newly diagnosed AL patients. Mixed, small and large blast cells
      predominated, with FAB M2 and L1 constituting the majority. All patients were
      positive for myeloid (M) markers and either B cell (B) (17 or 74%) or T cell (T)
      (8 or 34%) markers with two exceptional patients demonstrating trilineage
      phenotype. Six (50%) of studied M-B cases were positive for both IGH and TCR. In
      six (26%) patients myeloid lineage commitment was also demonstrable by electron
      cytochemistry. Abnormal findings were present in 19 (83%) patients by
      cytogenetics/FISH/molecular analysis as follows: t(9;22) (17%); MLL gene
      rearrangement (26%); deletion(6q) (13%); 12p11.2 (9%); numerical abnormalities
      (13%), and three (13%) new, previously unreported translocations
      t(X;6)(p22.3;q21); t(2;6)(q37;p21.3); and t(8;14)(p21;q32). In conclusion, the
      EGIL criteria for BAL appear robust when compared against molecular techniques
      that, if applied routinely, could aid in detecting BAL and help in risk
      stratification.

PMID- 16437135
TI  - Intensive consolidation versus oral maintenance therapy in patients 61 years or
      older with acute myeloid leukemia in first remission: results of second
      randomization of the AML HD98-B treatment Trial.

PMID- 16437136
TI  - Donor cell-derived acute myeloid leukemia after unrelated umbilical cord blood
      transplantation.

PMID- 16437137
TI  - Imperfect correlation between p53 dysfunction and deletion of TP53 and ATM in
      chronic lymphocytic leukaemia.

PMID- 16437138
TI  - Quantitative analysis of bone marrow CD34 cells in aplastic anemia and
      hypoplastic myelodysplastic syndromes.
AB  - Aplastic anemia (AA) and hypoplastic myelodysplastic syndromes (hMDS) are often
      difficult to distinguish. However, an accurate diagnosis is important because the
      prognosis and treatment of these diseases may differ. CD34+ hematopoietic
      progenitors are central to the pathogenesis of both disorders; they are the
      targets of the autoimmune attack in AA and neoplastic transformation in MDS. The
      aim of this study was to assess whether bone marrow CD34+ cell numbers could be
      used in differentiating between AA and hMDS. The percentage of bone marrow CD34+
      cells was normal or increased (mean -3.5+0.5%, range 1-7%) in 15 of 35 patients
      studied, and low (mean -0.13 +/- 0.02%, range 0.02-0.36%) in 20 of 35 patients.
      All patients with a normal or increased percentage of CD34+ cells were ultimately
      diagnosed with hMDS based on the detection of clonal cytogenetic abnormalities or
      progression to refractory anemia with excess blasts/acute myeloid leukemia. All
      patients with low marrow CD34+ cell numbers met standard clinical criteria for AA
      and have not demonstrated neoplastic transformation with follow-up.
      Quantification of marrow CD34+ cells may serve as an important tool for
      distinguishing between AA and hMDS.

PMID- 16437139
TI  - Relapse of acute promyelocytic leukemia with PML-RARalpha mutant subclones
      independent of proximate all-trans retinoic acid selection pressure.
AB  - Relapse of acute promyelocytic leukemia (APL) following all-trans retinoic acid
      (ATRA) therapy has been associated with the acquisition of mutations in the high
      affinity ATRA binding site in PML-RARalpha, but little information is available
      about the selection dynamics of the mutation-harboring subclones. In this study,
      6/18 patients treated with sequential ATRA and chemotherapy on protocol INT0129
      relapsed with complete replacement of the nonmutant pretreatment APL cell
      population by a PML-RARalpha mutant subclone. Two patients relapsed in proximity
      of ATRA treatment; however, in four patients there was a 6-48 month hiatus
      between the last ATRA treatment and relapse. The mutant subclones were not
      detectable in samples tested > or = 3 months before relapse at > or = 1 in 10(2)
      (10(-2)) sensitivity. In one patient, a functionally weak mutation was detected
      at 10(-4) sensitivity before therapy but only limited pre-relapse enrichment of
      the mutant subclone was observed on subsequent ATRA therapy. These results
      indicate that proximate ATRA selection pressure is frequently not the main
      determinant for the emergence of strongly dominant PML-RARalpha mutant subclones
      and suggest that APL subclones harboring PML-RARalpha mutations are predisposed
      to the acquisition of secondary genetic/epigenetic alterations that result in a
      growth/survival advantage.

PMID- 16437140
TI  - Acute myelogenous leukemia in a patient with Li-Fraumeni syndrome treated with
      valproic acid, theophyllamine and all-trans retinoic acid: a case report.

PMID- 16437141
TI  - Monoclonal B-cell lymphocytosis (MBL) in CLL families: substantial increase in
      relative risk for young adults.

PMID- 16437142
TI  - High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV
      regimen) as induction therapy in patients with resistant Philadelphia-positive
      acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid
      leukemia.
AB  - Imatinib combined with high-dose chemotherapy is now becoming the gold standard
      for treatment of Philadelphia chromosome-positive acute leukemias. However, in
      all studies imatinib dosage was tapered to 400-600 mg per day. We decided to
      initiate a clinical trial to evaluate an opposite strategy based on high-dose
      imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen
      (vincristine and dexamethasone), which we called the DIV induction regimen.
      Thirty-one patients (18 relapsing or refractory Ph+ acute lymphoblastic leukemias
      and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled.
      Complete remission (CR) was obtained in 28 out of 30 assessable patients. The
      median bcr-abl/abl ratio after the induction course was 0.1%. Median time to
      neutrophil recovery was 21 days. Fungus infections were observed in six patients
      out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine
      was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic
      stem cell transplantation after a median time of 78 days post-CR. Patients older
      than 55 years experienced a 90% CR rate without additional toxicities, suggesting
      the DIV regimen may also be proposed as a front line therapy in older patients.

PMID- 16437143
TI  - Immunotherapy of B-cell malignancies with genetically engineered human CD8+
      natural killer T cells.

PMID- 16437144
TI  - Mechanisms of apoptosis-induction by rottlerin: therapeutic implications for B
      CLL.
AB  - Constitutively activated signaling pathways contribute to the apoptosis-defect of
      B-CLL cells. Protein kinase C-delta is a permanently activated kinase and a
      putative downstream target of phosphatidylinositol-3 kinase in B-CLL. Blockade of
      protein kinase C-delta (PKC-delta) by the highly specific inhibitor rottlerin
      induces apoptosis in chronic lymphocytic leukaemia (CLL) cells. By co-culturing
      bone marrow stromal and CLL cells, we determined that the proapoptotic effect of
      rottlerin is not abolished in the presence of survival factors, indicating that a
      targeted therapy against PKC-delta might be a powerful approach for the treatment
      of CLL patients. The downstream events following rottlerin treatment engage
      mitochondrial and non-mitochondrial pathways and ultimately activate caspases
      that execute the apoptotic cell death. Herein we report that the inhibition of
      PKC-delta decreases the expression of the important antiapoptotic proteins Mcl-1
      and XIAP accompanied by a loss of the mitochondrial membrane potential Deltapsi.
      In addition, we discovered that ZAP-70-expressing cells are significantly more
      susceptible to rottlerin-induced cell death than ZAP-70 negative cells. We
      finally observed that rottlerin can augment cell toxicity induced by standard
      chemotherapeutic drugs. Conclusively, PKC-delta is a promising new target in the
      combat against CLL.

PMID- 16437145
TI  - TCRgammadelta+ large granular lymphocyte leukemias reflect the spectrum of normal
      antigen-selected TCRgammadelta+ T-cells.
AB  - T-cell large granular lymphocytes (LGL) proliferations range from reactive
      expansions of activated T cells to T-cell leukemias and show variable clinical
      presentation and disease course. The vast majority of T-LGL proliferations
      express TCRalphabeta. Much less is known about the characteristics and
      pathogenesis of TCRgammadelta+ cases. We evaluated 44 patients with clonal
      TCRgammadelta+ T-LGL proliferations with respect to clinical data,
      immunophenotype and TCR gene rearrangement pattern. TCRgammadelta+ T-LGL leukemia
      patients had similar clinical presentations as TCRalphabeta+ T-LGL leukemia
      patients. Their course was indolent and 61% of patients were symptomatic. The
      most common clinical manifestations were chronic cytopenias - neutropenia (48%),
      anemia (23%), thrombocytopenia (9%), pancytopenia (2%) - and to a lesser extent
      splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological
      (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2,
      CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56,
      CD11b, and CD11c. The Vgamma9/Vdelta2 immunophenotype was found in 48% of cases
      and 43% of cases was positive for Vdelta1, reflecting the TCR-spectrum of normal
      TCRgammadelta+ T-cells in adult PB. Identification of the well-defined post
      thymic Vdelta2-Jdelta1 selection determinant in all evaluable Vgamma9+/Vdelta2+
      patients, is suggestive of common (super)antigen involvement in the pathogenesis
      of these TCRgammadelta+ T-LGL leukemia patients.

PMID- 16437146
TI  - Near-tetraploid acute myeloid leukemias: an EGIL retrospective study of 25 cases.

PMID- 16437147
TI  - Reply to Herens et al.

PMID- 16437149
TI  - The GATA site-dependent hemogen promoter is transcriptionally regulated by GATA1
      in hematopoietic and leukemia cells.
AB  - Hemgn (a gene symbol for hemogen in mouse, EDAG in human and RP59 in rat) encodes
      a nuclear protein that is highly expressed in hematopoietic tissues and acute
      leukemia. To characterize its regulatory mechanisms, we examined the activities
      of a Hemgn promoter containing 2975 bp of 5' flanking sequence and 196 bp of 5'
      untranslated region (5' UTR) sequence both in vitro and in vivo: this promoter is
      preferentially activated in a hematopoietic cell line, not in nonhematopoietic
      cell lines, and is sufficient to drive the transcription of a lacZ transgene in
      hematopoietic tissues in transgenic mice. Mutagenesis analyses showed that the 5'
      UTR including two highly conserved GATA boxes is critical for the promoter
      activity. GATA1, not GATA2, binds to the GATA binding sites and transactivates
      the Hemgn promoter in a dose-dependent manner. Furthermore, the expression of
      human hemogen (EDAG) transcripts were closely correlated with levels of GATA1
      transcripts in primary acute myeloid leukemia specimens. This study suggests that
      the Hemgn promoter contains critical regulatory elements for its transcription in
      hematopoietic tissues and Hemgn is a direct target of GATA1 in leukemia cells.

PMID- 16437150
TI  - A death from Langerhans cell histiocytosis and tuberculosis in 18th Century
      Hungary - what palaeopathology can tell us today.

PMID- 16437151
TI  - Impaired activating receptor expression pattern in natural killer cells from
      patients with multiple myeloma.

PMID- 16437152
TI  - Universal N-glycosylation sites introduced into the B-cell receptor of follicular
      lymphoma by somatic mutation: a second tumorigenic event?

PMID- 16437153
TI  - Gain of chromosome 6p is an infrequent cause of increased PIM1 expression in B
      cell non-Hodgkin's lymphomas.

PMID- 16437154
TI  - A case of therapy-related acute myeloid leukemia associated with inv(16), with
      subsequent development of t(9;22).

PMID- 16437155
TI  - AtSufE is an essential activator of plastidic and mitochondrial desulfurases in
      Arabidopsis.
AB  - Iron-sulfur (Fe-S) clusters are vital prosthetic groups for Fe-S proteins
      involved in fundamental processes such as electron transfer, metabolism, sensing
      and signaling. In plants, sulfur (SUF) protein-mediated Fe-S cluster biogenesis
      involves iron acquisition and sulfur mobilization, processes suggested to be
      plastidic. Here we have shown that AtSufE in Arabidopsis rescues growth defects
      in SufE-deficient Escherichia coli. In contrast to other SUF proteins, AtSufE
      localizes to plastids and mitochondria interacting with the plastidic AtSufS and
      mitochondrial AtNifS1 cysteine desulfurases. AtSufE activates AtSufS and AtNifS1
      cysteine desulfurization, and AtSufE activity restoration in either plastids or
      mitochondria is not sufficient to rescue embryo lethality in AtSufE loss-of
      function mutants. AtSufE overexpression induces AtSufS and AtNifS1 expression,
      which in turn leads to elevated cysteine desulfurization activity, chlorosis and
      retarded development. Our data demonstrate that plastidic and mitochondrial Fe-S
      cluster biogenesis shares a common, essential component, and that AtSufE acts as
      an activator of plastidic and mitochondrial desulfurases in Arabidopsis.

PMID- 16437156
TI  - Phosphoinositide 3-kinase controls early and late events in mammalian cell
      division.
AB  - Phosphoinositide 3-kinase (PI3K) plays a crucial role in triggering cell
      division. To initiate this process, PI3K induces two distinct routes, of which
      one promotes cell growth and the other regulates cyclin-dependent kinases. Fine
      tuned PI3K regulation is also required for later cell cycle phases. Here, we
      review the multiple points at which PI3K controls cell division and discuss its
      impact on human cancer.

PMID- 16437157
TI  - Transcription regulation from a TATA and INR-less promoter: spatial segregation
      of promoter function.
AB  - The mode of regulation of class II genes that lack the known core promoter
      elements is presently unclear. Here, we studied one such example, the murine CD80
      gene. An unusual mechanism was revealed wherein the pre-initiation complex (PIC)
      first assembled on an upstream, NF-kappaB enhancer element. Notably, this
      assembly occurred independent of contributions from the core promoter domain, and
      resulted in a PIC that was competent for transcription initiation. Positioning
      was subsequently achieved by exploiting the intrinsic architecture of the
      promoter, by virtue of which the tethered PIC was spatially juxtaposed with the
      transcription initiation site. Bridging interactions then ensued, through protein
      protein contacts, which then enabled the elongation phase of CD80 transcription.

PMID- 16437158
TI  - Structural basis for myosin V discrimination between distinct cargoes.
AB  - Myosin V molecular motors move cargoes on actin filaments. A myosin V may move
      multiple cargoes to distinct places at different times. The cargoes attach to the
      globular tail of myosin V via cargo-specific receptors. Here we report the
      crystal structure at 2.2 A of the myosin V globular tail. The overall tertiary
      structure has not been previously observed. There are several patches of highly
      conserved regions distributed on the surface of the tail. These are candidate
      attachment sites for cargo-specific receptors. Indeed, we identified a region of
      five conserved surface residues that are solely required for vacuole inheritance.
      Likewise, we identified a region of five conserved surface residues that are
      required for secretory vesicle movement, but not vacuole movement. These two
      regions are at opposite ends of the oblong-shaped cargo-binding domain, and
      moreover are offset by 180 degrees. The fact that the cargo-binding areas are
      distant from each other and simultaneously exposed on the surface of the globular
      tail suggests that major targets for the regulation of cargo attachment are
      organelle-specific myosin V receptors.

PMID- 16437159
TI  - Baboon/dSmad2 TGF-beta signaling is required during late larval stage for
      development of adult-specific neurons.
AB  - The intermingling of larval functional neurons with adult-specific neurons during
      metamorphosis contributes to the development of the adult Drosophila brain. To
      better understand this process, we characterized the development of a dorsal
      cluster (DC) of Atonal-positive neurons that are born at early larval stages but
      do not undergo extensive morphogenesis until pupal formation. We found that
      Baboon(Babo)/dSmad2-mediated TGF-beta signaling, known to be essential for
      remodeling of larval functional neurons, is also indispensable for proper
      morphogenesis of these adult-specific neurons. Mosaic analysis reveals slowed
      development of mutant DC neurons, as evidenced by delays in both neuronal
      morphogenesis and atonal expression. We observe similar phenomena in other adult
      specific neurons. We further demonstrate that Babo/dSmad2 operates autonomously
      in individual neurons and specifically during the late larval stage. Our results
      suggest that Babo/dSmad2 signaling prior to metamorphosis may be widely required
      to prepare neurons for the dynamic environment present during metamorphosis.

PMID- 16437160
TI  - Recruitment of Tup1p and Cti6p regulates heme-deficient expression of Aft1p
      target genes.
AB  - In the budding yeast Saccharomyces cerevisiae, transcription of genes encoding
      for the high-affinity iron (FET3, FTR1) and copper (CTR1) transporters does not
      occur in the absence of heme. We show that the Aft1p binding region of the FET3
      promoter or the Mac1p binding region of the CTR1 promoter is necessary and
      sufficient to mediate heme-deficient repression. Transcription is repressed in
      the absence of heme, and a genetic screen identified Tup1p and Hda1p as being
      required for transcriptional repression. In contrast to FET3 and CTR1, Aft1p
      target genes ARN1 and FIT1 are transcribed in the absence of heme. A 14 bp
      sequence in the ARN1 promoter is necessary and sufficient to permit transcription
      in the absence of heme. Transcription in the absence of heme required the
      presence of Cti6p to overcome the effect of Tup1p, and Cti6p was recruited to the
      ARN1 promoter in the absence of heme. We hypothesize that transcription of the
      siderophore transporter ARN1 permits yeast to accumulate iron in the absence of
      oxygen and to deny iron to competing organisms.

PMID- 16437162
TI  - Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human
      progressive deafness.
AB  - KCNQ4 is an M-type K+ channel expressed in sensory hair cells of the inner ear
      and in the central auditory pathway. KCNQ4 mutations underlie human DFNA2
      dominant progressive hearing loss. We now generated mice in which the KCNQ4 gene
      was disrupted or carried a dominant negative DFNA2 mutation. Although KCNQ4 is
      strongly expressed in vestibular hair cells, vestibular function appeared normal.
      Auditory function was only slightly impaired initially. It then declined over
      several weeks in Kcnq4-/- mice and over several months in mice carrying the
      dominant negative allele. This progressive hearing loss was paralleled by a
      selective degeneration of outer hair cells (OHCs). KCNQ4 disruption abolished the
      I(K,n) current of OHCs. The ensuing depolarization of OHCs impaired sound
      amplification. Inner hair cells and their afferent synapses remained mostly
      intact. These cells were only slightly depolarized and showed near-normal
      presynaptic function. We conclude that the hearing loss in DFNA2 is predominantly
      caused by a slow degeneration of OHCs resulting from chronic depolarization.

PMID- 16437161
TI  - Global and gene-specific analyses show distinct roles for Myod and Myog at a
      common set of promoters.
AB  - We used a combination of genome-wide and promoter-specific DNA binding and
      expression analyses to assess the functional roles of Myod and Myog in regulating
      the program of skeletal muscle gene expression. Our findings indicate that Myod
      and Myog have distinct regulatory roles at a similar set of target genes. At
      genes expressed throughout the program of myogenic differentiation, Myod can bind
      and recruit histone acetyltransferases. At early targets, Myod is sufficient for
      near full expression, whereas, at late expressed genes, Myod initiates regional
      histone modification but is not sufficient for gene expression. At these late
      genes, Myog does not bind efficiently without Myod; however, transcriptional
      activation requires the combined activity of Myod and Myog. Therefore, the role
      of Myog in mediating terminal differentiation is, in part, to enhance expression
      of a subset of genes previously initiated by Myod.

PMID- 16437163
TI  - Growth factor pleiotropy is controlled by a receptor Tyr/Ser motif that acts as a
      binary switch.
AB  - Pleiotropism is a hallmark of cytokines and growth factors; yet, the underlying
      mechanisms are not clearly understood. We have identified a motif in the
      granulocyte macrophage-colony-stimulating factor receptor composed of a tyrosine
      and a serine residue that functions as a binary switch for the independent
      regulation of multiple biological activities. Signalling occurs either through
      Ser585 at lower cytokine concentrations, leading to cell survival only, or
      through Tyr577 at higher cytokine concentrations, leading to cell survival as
      well as proliferation, differentiation or functional activation. The
      phosphorylation of Ser585 and Tyr577 is mutually exclusive and occurs via a
      unidirectional mechanism that involves protein kinase A and tyrosine kinases,
      respectively, and is deregulated in at least some leukemias. We have identified
      similar Tyr/Ser motifs in other cell surface receptors, suggesting that such
      signalling switches may play important roles in generating specificity and
      pleiotropy in other biological systems.

PMID- 16437164
TI  - HIV and the chemokine system: 10 years later.
AB  - The unexpected encounter, 10 years ago, between human immunodeficiency virus
      (HIV) and the chemokine system has dramatically advanced our understanding of the
      pathogenesis of AIDS, opening new perspectives for the development of effective
      prophylactic and therapeutic measures. To initiate infection, the HIV-1 external
      envelope glycoprotein, gp120, sequentially interacts with two cellular receptors,
      CD4 and a chemokine receptor (or coreceptor) like CCR5 or CXCR4. This peculiar
      two-stage receptor-interaction strategy allows gp120 to maintain the highly
      conserved coreceptor-binding site in a cryptic conformation, protected from
      neutralizing antibodies. The differential use of CCR5 and CXCR4 defines three HIV
      1 biological variants (R5, R5X4, X4), which vary in their prevalence during the
      disease course. The evolutionary choice of HIV-1 to exploit chemokine receptors
      as cellular entry gateways has turned their chemokine ligands into endogenous
      antiviral factors that variably modulate viral transmission, disease progression
      and vaccine responses. Likewise, the natural history of HIV-1 infection is
      influenced by specific polymorphisms of chemokine and chemokine-receptor genes.
      The imminent clinical availability of coreceptor-targeted viral entry inhibitors
      raises new hope for bridging the gap towards a definitive cure of HIV infection.

PMID- 16437165
TI  - Membrane and soluble substrates of the Doa10 ubiquitin ligase are degraded by
      distinct pathways.
AB  - The yeast Doa10 ubiquitin (Ub) ligase resides in the endoplasmic reticulum
      (ER)/nuclear envelope (NE), where it functions in ER-associated degradation
      (ERAD). Doa10 substrates include non-ER proteins such as the transcription factor
      Mat alpha2. Here, we expand the range of Doa10 substrates to include a defective
      kinetochore component, a mutant NE membrane protein, and a substrate-regulated
      human ER enzyme. For all these substrates, Doa10 requires two Ub-conjugating
      enzymes, Ubc6 and Ubc7, as well as the Ubc7 cofactor Cue1. Based on a novel
      genomic screen of a comprehensive gene deletion library and other data, these
      four proteins appear to be the only nonessential and nonredundant factors
      generally required for Doa10-mediated ubiquitination. Notably, the Cdc48 ATPase
      facilitates degradation of membrane-embedded Doa10 substrates, but is not
      required for any tested soluble Doa10 substrates. This distinction is maintained
      even when comparing membrane and soluble proteins bearing the same degradation
      signal. Thus, while Doa10 ubiquitinates both membrane and soluble proteins, the
      mechanisms of subsequent proteasome targeting differ.

PMID- 16437166
TI  - Interleukin-18, neutrophils, and ANCA.
AB  - Hewins et al. show that IL-18 is expressed in the kidneys of patients with ANCA
      associated glomerulonephritis, and that IL-18 primes neutrophils via p38 MAPK.
      These findings suggest a role for IL-18, including IL-18-induced T(H)1
      polarization and IFN-gamma production, in the progression of ANCA disease.

PMID- 16437168
TI  - Metal complexes in medicinal chemistry: new vistas and challenges in drug design.
AB  - An overview is presented of selected metal-based pharmaceuticals, either
      diagnostic or therapeutic, with emphasis on specific attributes and in vivo
      interactions of these compounds relevant to their use in medicinal applications.
      Both the advantages and the challenges of this approach are outlined, with
      possibilities for future developments accentuated.

PMID- 16437169
TI  - A 3D porous lanthanide-fumarate framework with water hexamer occupied cavities,
      exhibiting a reversible dehydration and rehydration procedure.
AB  - [Sm2(fumarate)3(H2O)4] x 3 H2O, a new porous pillared layer framework with 0D
      cavities for the accommodation of chair-like hexameric water clusters, possesses
      three kinds of fumarate ligand with their two COO ends adopting different
      coordination modes and shows reversible de- and re-hydration behavior.

PMID- 16437170
TI  - A dinuclear triple-stranded helicate with a bis(benzene-o-dithiolato) ligand.
AB  - The bis(benzene-o-dithiol) ligand H4-1 reacts with Ti4+ in a self-assembly
      reaction to give the dinuclear triple-stranded helicate [Ti2(1)3]4- which is the
      first helicate build exclusively from benzene-o-dithiolato donor groups.

PMID- 16437171
TI  - Reductions by titanium(II) as catalyzed by titanium(IV).
AB  - The cobalt(III) complexes, [(NH3)5CoBr]2+ and [(NH3)5CoI]2+ are reduced by Ti(II)
      solutions containing Ti(IV), generating nearly linear (zero-order) profiles that
      become curved only during the last few percent of reaction. Other Co(III)-Ti(II)
      systems exhibit the usual exponential traces with rates proportional to
      [Co(III)]. Observed kinetics of the biphasic catalyzed Ti(II)-Co(III)Br and
      Ti(II)-Co(III)I reactions support the reaction sequence: [Ti(II)(H20)n]2+ +
      [Ti(IV)F5]- (k1)<==>(k -1) [Ti(II)(H2O)(n-1)]2+ + [(H2O)Ti(IV)F5]-,
      [Ti(II)(H2O)(n-1)]2+ + Co(III) (k2)--> Ti(III) + Co(II) with rates determined
      mainly by the slow Ti(IV)-Ti(II) ligand exchange (k1 = 9 x 10(-3) M(-1) s(-1) at
      22 degrees C). Computer simulations of the catalyzed Ti(II)-Co(III) reaction in
      perchlorate-triflate media yield relative rates for reduction by the proposed
      active [Ti(II)(H2O)(n-1)]2+ intermediate; k(Br)/k(I) = 8.

PMID- 16437172
TI  - 'Pincer' dicarbene complexes of some early transition metals and uranium.
AB  - The complexes [(C-N-C)MX(n)(thf)(m)] with the 'pincer' 2,6
      bis(imidazolylidene)pyridine, (C-N-C) = 2,6-bis(arylimidazol-2-ylidene)pyridine,
      aryl = 2,6-Pr(i)2C6H3, M = V, X = Cl, n = 2, m = 1 1a; M = Cr, X = Cl, n = 2, m =
      0, 2a, X = Br, 2b; M = Mn, X = Br, n = 2, m = 0, 3; M = Nb, X = Cl, n = 3, m = 0,
      4; and M = U, X = Cl, n = 4, m = 0, 5, were synthesised by (a) substitution of
      labile tmed (1a), thf (2a, 3, 5) or dme (4) by free (C-N-C) or by (b) reaction of
      the bisimidazolium salt (CH-N-CH)Br2 with {Cr[N(SiMe3)2]2(thf)2} followed by
      amine elimination (2b). Attempted alkylation of 1a, 2, 3a and 4 with Grignard or
      alkyl lithiums gave intractable mixtures, and in one case [reaction of 1a with
      (mesityl)MgBr] resulted in exchange of Cl by Br (1b). Oxidation of 1a or [(C-N
      C)VCl3] with 4-methylmorpholine N-oxide afforded the trans-V(C-N-C)(=O)Cl2, 6,
      which by reaction with AgBF4 in MeCN gave trans-[V(C-N-C)(=O)(MeCN)2][BF4]2, 7.
      Reaction of 1a with p-tolyl azide gave trans-V(C-N-C)(=N-p-tolyl)Cl2 8. The
      complex trans-Ti(C-N-C)(=NBu(t))Cl2, 9, was prepared by substitution of the
      pyridine ligands in Ti(NBu(t))Cl2(py)3 by C-N-C.

PMID- 16437173
TI  - Probing the mechanism of hypoxia selectivity of copper bis(thiosemicarbazonato)
      complexes: DFT calculation of redox potentials and absolute acidities in
      solution.
AB  - Density functional theory (DFT) calculations have been performed using the
      uB3LYP/6-31++G(d,p) model to calculate the solution phase one-electron reduction
      potentials (E(calc)) and absolute pKa values of a series of copper
      bis(thiosemicarbazonato) complexes. The effects of solvation in water and
      dimethylsulfoxide (DMSO) are incorporated as a self-consistent reaction field
      (SCRF) using the integral equation formalism polarisable continuum model (IEFPCM)
      and are found to be essential for quantitative agreement with an average error in
      E(calc) of -0.02 V compared to experiment. The bonding and spin densities are
      examined through the use of Natural Bond Order analysis and the results used to
      rationalise the calculated and observed reduction potentials. Calculated
      estimates of pKa values of several copper(II) species are presented and their
      implications for the mechanisms of transport and trapping within hypoxic cells
      are considered. Reduction is found to be a prerequisite for protonation of the
      complexes which suggests their transport in the blood stream as neutral species,
      and the mechanistic sequence is identified as a sequential electrochemical
      chemical (EC) process. The complex equilibria of protonation, reoxidation and
      dissociation are discussed and the copper(I) diprotonated, cationic complex of
      diacetyl bis(4-methyl-3-thiosemicarbazonato)copper(II), Cu(I)ATSMH2(+), is
      identified as a possible candidate for the initial species trapped in hypoxic
      cells.

PMID- 16437174
TI  - A colorimetric chemosensor for both fluoride and transition metal ions based on
      dipyrrolyl derivative.
AB  - The synthesis, characterization and ion binding studies of 2,3-di(1H-2
      pyrrolyl)pyrido[2,3-b]pyrazine (1) have been described. 1, which has been
      targeted with a view to sensing both F- and transition metal ions, exhibits
      binding-induced color changes from yellowish green to red/brown observable by the
      naked eye. The binding site for the metal ion in the system has been
      unambiguously established by single-crystal X-ray diffraction study of a Ni(II)
      complex of 1. While the estimated value of the binding constant of 1 with F- is
      4.9 x 10(3) M(-1), the binding constants for the cations are found to be two
      orders higher in magnitude in acetonitrile. Even though 1 possesses two separate
      binding sites for F- and metal ions, it is shown that the presence of the cation
      influences the binding of the anion and vice versa. The binding constant values
      of an ion in the presence of oppositely charged species are measured to be
      significantly lower.

PMID- 16437175
TI  - Manipulation of reaction pathways in redox transmetallation-ligand exchange
      syntheses of lanthanoid(II)/(III) aryloxide complexes.
AB  - Redox transmetallation/ligand exchange reactions of lanthanoid metals (Ln),
      Hg(C6F5)2 and HOAr(OMe) (Ar(OMe) = C6H2-2,6-Bu(t)-4-OMe), in thf
      (tetrahydrofuran) gave, for Ln = Yb, [Yb(OAr(OMe))2(thf)3], and for Ln = Sm, a
      mixture of [Sm(II)(OAr(OMe))2(thf)3] and mainly [Sm(III)(Ar(OMe))3(thf)] x thf. X
      Ray structure determinations show the divalent complexes to have distorted square
      pyramidal stereochemistry with transoid thf and OAr(OMe) ligands in the basal
      plane. Treatment of [Yb(OAr(OMe))2(thf)3] with diethyl ether or PhMe at room
      temperature gave [Yb(OAr(OMe))2] or [Yb(OAr(OMe))2] x 0.5 PhMe. For lanthanoids
      Ln = Nd, Er or Y, the reactions with Hg(C6F5)2 and HOAr(OMe) yielded complex
      product mixtures, from one of which the novel erbium aryloxide fluoride cage
      [Er3(OAr(OMe))4(mu2-F)3(mu3-F)2(thf)4] x thf x 0.5 C6H14 was isolated. The cage
      core consists of a triangle of Er atoms joined to two mu3-fluoride ligands and
      three further mu2-fluorides bridge adjacent Er atoms. One of the Er atoms is six
      coordinate with additionally two OAr(OMe) ligands whilst the other two have one
      OAr(OMe) and two thf ligands and are seven coordinate. Substitution of Hg(C6F5)2
      by Hg(CCPh)2 in the redox transmetallation/ligand exchange reactions gave the new
      derivatives [Ln(OAr(OMe))3(thf)] x thf (Ln = La, Pr, Nd, Sm, Gd, Ho) in good
      yields whilst Ln = Yb gave [Yb(OAr(OMe))2(thf)3]. Recrystallisation of
      [Sm(OAr(OMe))3(thf)] x thf from dme (1,2-dimethoxyethane) yielded
      [Sm(OAr(OMe))3(dme)]. Structural characterisation of [Ln(OAr(OMe))3(thf)] x thf
      (Ln = Nd, Ho) and [Sm(OAr(OMe))3(dme)] showed monomeric four-coordinate distorted
      tetrahedral and five-coordinate distorted square-pyramidal complexes
      respectively. For the smaller lanthanoids Ln = Y, Er or Lu, reactions with
      Hg(CCPh)2 and HOAr(OMe) gave the mixed aryloxide/alkynide complexes
      [Ln(OAr(OMe))2(CCPh)(thf)2]. Oxidation of the divalent ytterbium aryloxide
      [Yb(OAr(OMe))2(thf)3] by Hg(CCPh)2 in thf gave the analogous
      [Yb(OAr(OMe))2(CCPh)(thf)2]. The erbium alkynide [Er(OAr(OMe))2(CCPh)(thf)2] x
      0.25 C6H14 has distorted square-pyramidal stereochemistry with transoid OAr(OMe)
      and thf ligands in the basal plane and a rare (for Ln) terminal alkynide ligand
      in the apical position. The reactive Lu-C bond in the [Lu(OAr(OMe))2(CCPh)(thf)2]
      complexes could be slowly cleaved by free HOAr(OMe) in hydrocarbon solvents,
      yielding Lu(OAr(OMe))3 species and fortuitous partial hydrolysis of
      [Er(Ar(OMe))2(CCPh)(thf)2] gave the dimeric [Er(OAr(OMe))2(mu-OH)2]2.

PMID- 16437176
TI  - Absorption spectroscopy and binding constants for first-row transition metal
      complexes of a DOPA-containing peptide.
AB  - A diverse array of biological systems incorporate 3,4-dihydroxyphenlyalanine
      (DOPA) into proteins and small molecules for cross-linking and material
      generation. Marine worm eggshells, sea squirt wound plugs, and marine mussel
      adhesives may all be formed by combining DOPA-containing molecules with high
      levels of metals. In order to provide model systems for characterizing these
      biomaterials, we carried out a study on metal binding to a DOPA-containing
      peptide. Ultraviolet-visible absorption spectra are presented for the AdopaTP
      peptide binding to Fe3+, V3+, VO2+, Mn3+, Ti4+, Cu2+, Co2+, and Ni2+ in mono,
      bis, and where applicable, tris coordination modes. Association constants were
      determined for selected metal ions binding to the peptide. In general, the
      spectroscopic and binding properties of this DOPA-containing peptide were found
      to be similar to those of catechol.

PMID- 16437177
TI  - Structural diversity in iron(II) complexes of 2,6-di(pyrazol-1-yl)pyridine and
      2,6-di(3-methylpyrazol-1-yl)pyridine.
AB  - The syntheses, magnetochemistry and crystallography of [Fe(L1)2]I0.5[I3]1.5 (1),
      [Fe(L1)2][Co(C2B9H11)2]2 (2) and [Fe(L2)2][SbF6]2 (3) (L1 = 2,6-di(pyrazol-1
      yl)pyridine; L2 = 2,6-di(3-methylpyrazol-1-yl)pyridine) are described. Compounds
      1 and 3 are high-spin between 5-300 K. For 1, this reflects a novel variation of
      an angular Jahn-Teller distortion at the iron centre, which traps the molecule in
      its high-spin state. No such distortion is present in 3; rather, the high-spin
      nature of this compound may reflect ligand conformational strain caused by an
      intermolecular steric contact in the crystal lattice. Compound 2 exhibits a
      gradual high --> low spin transition upon cooling with T(1/2) = 318 +/- 3 K, that
      is only 50% complete. This reflects the presence of two distinct, equally
      populated iron environments in the solid. One of these unique iron centres adopts
      the same angular structural distortion shown by 1 and so is trapped in its high
      spin state, while the other, which undergoes the spin-crossover, has a more
      regular coordination geometry. In contrast with 3, the solvated salts
      [Fe(L2)2][BF4]2 x 4 CH3CN and [Fe(L2)2][ClO4]2 x (CH3)2CO both undergo gradual
      thermal spin-transitions centred at 175 +/- 3 K.

PMID- 16437178
TI  - Reactivity of cyclooligophosphanes: synthesis and structural characterisation of
      cyclo-1,4-(BH3)2(P4Ph4CH2) and cyclo-1,2-(BH3)2(P5Ph5).
AB  - The borane complexes cyclo-1,4-(BH3)2(P4Ph4CH2) (3) and cyclo-1,2-(BH3)2(P5Ph5)
      (4) were prepared by reaction of cyclo-(P4Ph4CH2) and cyclo-(P5Ph5) with
      BH3(SMe2). Only the 2:1 complexes 3 and 4 were isolated, even when an excess of
      the borane source was used. In solution, 3 exists as a mixture of the two
      diastereomers (R(P)*,S(P)*,S(P)*,R(P)*)-(+/-)-3 and (R(P)*,R(P)*,R(P)*,R(P)*)-(+/
      )-3. However, in the solid state the (R(P)*,S(P)*,S(P)*,R(P)*)-(+/-) diastereomer
      is the major stereoisomer. Similarly, while only one isomer of 4 is observed in
      its X-ray structure, NMR spectroscopic investigations reveal that it forms a
      complex mixture of isomers in solution. 3 may be deprotonated with tBuLi to give
      the lithium salt cyclo-1,4-(BH3)2(P4Ph4CHLi) (3 x Li), though this could not be
      isolated in pure form.

PMID- 16437179
TI  - Coordination frameworks constructed from bipyridyl piperazine and MCl2 (M = Co,
      Ni, Zn): structural characterization and optical properties.
AB  - Three metal-organic polymers, [CoCl2(bpfp)]n 1, {[NiCl2(bpfp)2](H2O)3}n 2 and
      [ZnCl2(bpfp)]n 3 (bpfp = N,N'-bis(3-pyridylformyl)piperazine), are formed by the
      self-assembly of the flexible bpfp with MCl2 (M = Co, Ni, Zn), respectively. X
      Ray single-crystal structural analysis reveals that polymer 1 exhibits a novel
      grid network, in which the grid is composed of segments of bpfp and cobalt ions.
      Polymer 2 consists of 2D rhombohedral grids, the dimensions of the grid are
      15.782 x 12.434 A2 and the diagonal-to-diagonal distances are 13.186 x 25.169 A2.
      In polymer 3, infinite wavelike chains are extended to 2D supramolecular arrays
      via C-H...Cl hydrogen bonds. The third-order nonlinear optical (NLO) behaviors of
      1-3 and bpfp were investigated in dilute DMF solution by Z-scan measurement. The
      results show that 1, 2 and 3 exhibit good third-order NLO properties, which are
      quite different from bpfp that shows weak NLO behavior. This paper demonstrates
      that metal ions can strongly influence the crystal structures and third-order NLO
      properties of polymers.

PMID- 16437180
TI  - Comments on the ring-opening polymerization of morpholine-2,5-dione derivatives
      by various metal catalysts and characterization of the products formed in the
      reactions involving R2SnX2, where X = OPr(i) and NMe2 and R = Bu(n), Ph and p
      Me2NC6H4.
AB  - (3S,6S)-3-Isopropyl-6-methyl-morpholine-2,5-dione (1), and (3S,6S)-3,6-dimethyl
      morpholine-2,5-dione (2), do not enter into ring-opening polymerization reactions
      with metal catalyst precursors commonly employed for lactides, and with Sn(II)
      octanoate, only low molecular weight oligomers are obtained. Reactions with
      R2SnX2 compounds, where R = Ph, Bu(n) and p-Me2NC6H4 and X = OPr(i) or NMe2,
      reveal that ring-opening of the morpholine-2,5-diones does occur, but that
      polymerization is terminated by the formation of kinetically-inert products such
      as {Ph2Sn[mu,eta(3)-OCH(Me)CONCH(Pr(i))COOPr(i)]}2 (3), and {[Bu(n))2Sn[mu,eta(3)
      OCH(Me)CONCH(Me)CONMe2]}2 (4), with elimination of HX. Ph3SnOPr(i) is seen to
      react reversibly with morpholine-2,5-diones in toluene-d8 by 1H NMR spectroscopy
      while (Bu(n))3SnNMe2 reacts by ring opening to give
      (Bu(n))3SnOCH(Me)C(O)NHCHMeC(O)NMe2. The new organotin compounds have been
      characterized by 1H, 13C{1H} and 118Sn NMR spectroscopy and compounds 1, 2, 3 and
      4 by single crystal X-ray crystallography.

PMID- 16437181
TI  - A time-dependent density functional theory investigation on the nature of the
      electronic transitions involved in the nonlinear optical response of
      [Ru(CF3CO2)3T] (T = 4'-(C6H4-p-NBu2)-2,2':6',2''-terpyridine).
AB  - We report a theoretical study based on density functional theory (DFT) and time
      dependent DFT (TDDFT) calculations on the nature and role of the absorption bands
      involved in the nonlinear optical response of the complexes [Ru(CF3CO2)3T] (T =
      T1, T2; T1 = 4'-(C6H4-p-NBu2)-2,2':6',2''-terpyridine, T2 = 4'-(C6H4-p-NMe2)
      2,2':6',2''-terpyridine). Geometry optimizations, performed without any symmetry
      constraints, confirm a twisting of the -C6H4-p-NBu2 moiety with respect to the
      plane of the chelated terpyridine. Despite this lack of strong pi interaction,
      TDDFT excited states calculations of the electronic spectrum in solution provide
      evidence of a relevant role of the NBu2 donor group in the low-energy LMCT band
      at 911 nm. Calculations also show that the two bands at higher energy (508 and
      455 nm) are not attributable only to LMCT and ILCT transitions but to a mixing of
      ILCT/MLCT and ILCT/pi-pi* transitions, respectively. The 911 nm LMCT band,
      appearing at lower wavelength of the second harmonic (670 nm) of the EFISH
      experiment, controls the negative value of the second-order NLO response. This is
      confirmed by our calculations of the static component beta0(zzz) of the quadratic
      hyperpolarizability tensor, showing a large positive value. In addition we have
      found that the increase of the dipole moment upon excitation occurs, in all the
      characterized transitions, along the dipole moment axis, thus explaining why the
      EFISH and solvatochromic experimental values of the quadratic hyperpolarizability
      agree as sign and value.

PMID- 16437182
TI  - Unsymmetrically N,N'-substituted saturated carbenes: synthesis, reactivity and
      preparation of a rhodium(I) carbene complex.
AB  - A versatile synthesis of unsymmetrically N,N'-substituted saturated carbenes is
      described. The novel racemic imidazolidin-2-ylidenes rac-5 have been synthesized
      by reductive desulfurization of the corresponding imidazolidin-2-thiones rac-4.
      The thiones were prepared in two reaction steps from aldimines and secondary
      amines. Three different substituents at N1, N3 and C4 of the five-membered N
      heterocyclic ring can be introduced by choice of suitable aldimines and secondary
      amines. The dimerization behaviour (diaminocarbene/enetetramine equilibrium) for
      the unsymmetrically N,N'-substituted imidazolidin-2-ylidenes has been
      investigated by NMR spectroscopy. Unsymmetrically N-iPr and N-iBu substituted N
      heterocyclic carbenes undergo a slow dimerization, whereas N-tBu substituted
      derivatives are stable as monomeric carbenes indefinitely. The carbene ligand rac
      5d has been coordinated to rhodium(I) to give the square-planar rhodium carbene
      complex [Cl(cod)Rh(rac-5d)]rac-6d which has been characterized by an X-ray
      diffraction analysis.

PMID- 16437183
TI  - Characterization of two cytochrome oxidase operons in the marine cyanobacterium
      Synechococcus sp. PCC 7002: inactivation of ctaDI affects the PS I:PS II ratio.
AB  - Cyanobacteria have versatile electron transfer pathways and many of the proteins
      involved are functional in both respiratory and photosynthetic electron
      transport. Examples of such proteins include the cytochrome b (6) f complex, NADH
      dehydrogenase and cytochrome oxidase complexes. In this study we have cloned and
      sequenced two gene clusters from the marine cyanobacterium Synechococcus sp. PCC
      7002 that potentially encode heme-copper cytochrome oxidases. The ctaCIDIEI and
      ctaCIIDIIEII gene clusters are most similar to two related gene clusters found in
      the freshwater cyanobacterial strain Synechocystis sp. PCC 6803. Unlike
      Synechocystis sp. PCC 6803, Synechococcus sp. PCC 7002 does not have a cydAB-like
      gene cluster which encodes a quinol oxidase. The ctaCIDIEI and ctaCIIDIIEII gene
      clusters were transcribed polycistronically, although the levels of transcripts
      for the ctaCIIDIIEII gene cluster were lower than those of the ctaCIDIEI gene
      cluster. The ctaDI and ctaDII coding sequences were interrupted by interposon
      mutagenesis and full segregants were isolated and characterized for both single
      and double mutants. Growth rates, chlorophyll and carotenoid contents, oxygen
      consumption and oxygen evolution were examined in the wild type and mutant
      strains. Differences between the wild type and mutant strains observed in 77 K
      fluorescence spectra and in pulse-amplified modulated (PAM) fluorescence studies
      suggest that the cyanobacterial oxidases play a role in photoinhibition and high
      light tolerance in Synechococcus sp. PCC 7002.

PMID- 16437184
TI  - Significance of the excitonic intensity borrowing in the J-/H-aggregates of
      bacteriochlorophylls/chlorophylls.
AB  - A quantitative analysis of the excitonic intensity borrowing for the J-/H
      aggregates of the bacteriochlorophylls/chlorophylls (BChls/Chls) in specific, and
      of porphyrins in general, is presented. The analysis is based on the argument
      that the mixing between the two energetically well-separated bands, such as the Q
      and B bands of BChls/Chls, should be considered important if the aggregated
      system possesses an excitonic superstate. A remarkably simple explanation of the
      significance of the excitonic intensity borrowing is given: superhyperchromism is
      manifested by the mediation of interband coupling between the superstates in the
      two well-separated bands of such aggregates. A comprehensive discussion on the
      significance of superhyperchromism and on its size-dependence is provided in
      connection with its effects on the absorption spectra of the BChl/Chl J- and H
      aggregates.

PMID- 16437185
TI  - Models for proton-coupled electron transfer in photosystem II.
AB  - The coupling of proton and electron transfers is a key part of the chemistry of
      photosynthesis. The oxidative side of photosystem II (PS II) in particular seems
      to involve a number of proton-coupled electron transfer (PCET) steps in the S
      state transitions. This mini-review presents an overview of recent studies of
      PCET model systems in the authors' laboratory. PCET is defined as a chemical
      reaction involving concerted transfer of one electron and one proton. These are
      thus distinguished from stepwise pathways involving initial electron transfer
      (ET) or initial proton transfer (PT). Hydrogen atom transfer (HAT) reactions are
      one class of PCET, in which H(+) and e (-) are transferred from one reagent to
      another: AH + B --> A + BH, roughly along the same path. Rate constants for many
      HAT reactions are found to be well predicted by the thermochemistry of hydrogen
      transfer and by Marcus Theory. This includes organic HAT reactions and reactions
      of iron-tris(alpha-diimine) and manganese-(mu-oxo) complexes. In PS II, HAT has
      been proposed as the mechanism by which the tyrosine Z radical (Y(Z)*) oxidizes
      the manganese cluster (the oxygen evolving complex, OEC). Another class of PCET
      reactions involves transfer of H(+) and e (-) in different directions, for
      instance when the proton and electron acceptors are different reagents, as in AH
      B + C(+) --> A-HB(+) + C. The oxidation of Y(Z) by the chlorophyll P680 + has
      been suggested to occur by this mechanism. Models for this process - the
      oxidation of phenols with a pendent base - are described. The oxidation of the
      OEC by Y(Z)* could also occur by this second class of PCET reactions, involving
      an Mn-O-H fragment of the OEC. Initial attempts to model such a process using
      ruthenium-aquo complexes are described.

PMID- 16437187
TI  - Ruptured intracranial dermoid cysts.
AB  - Rupture of intracranial dermoid cysts (RICDC) is a rare phenomenon. The mechanism
      of rupture, pathophysiology of fat in the ventricles and subarachnoid spaces,
      possible complications, and proper management of such conditions are proposed on
      the basis of a review of the literature and experience with two cases of ruptured
      intracranial dermoid cysts (One was in the pineal region, while another was in
      the fourth ventricle). It is concluded that rupture of intracranial dermoid cysts
      is usually spontaneous and non-fatal. Persistence of fat in the subarachnoid
      spaces postoperatively may last asymptomatically for years. Surgery is the only
      way to deal with these benign lesions. If the capsule is adherent to vital areas,
      incomplete removal is advised as recurrence and malignant transformation are
      unlikely to occur.

PMID- 16437186
TI  - Emergency management of epidural haematoma through burr hole evacuation and
      drainage. A preliminary report.
AB  - BACKGROUND: Blood clot evacuation through an osteoplastic craniotomy, a procedure
      requiring neurosurgical expertise and modern medical facilities, is the accepted
      method for treatment of a pure traumatic epidural haematoma following closed head
      injury. In certain emergency situations and/or in less sophisticated settings,
      however, use of this procedure may not be feasible. The present study was
      undertaken to ascertain whether placement of a burr hole and drainage under
      negative pressure constituted a rapid, effective and safe approach to manage
      patients with simple epidural haematomas. METHODS: Thirteen patients suffering
      from a traumatic epidural haematoma were treated from January, 1999 to October,
      2002. Twelve patients presented with skull fracture but no fracture was
      depressed. Placement of flexible tubes through a burr hole, followed by
      continuous suction under negative pressure, enabled aspiration of the clot and
      drainage of the cavity. In 8 cases, the procedure was performed under local
      anaesthesia with 2% Xylocaine and with intravenous sedation with propofol as
      needed. The operative procedure was accomplished within 30 min, and the drainage
      tube was left in place for 3-5 days. CT scans were performed daily from days 1 to
      5. RESULTS: In 11 of 13 cases, clots were evacuated successfully and patients
      regained consciousness within 2 hours. Recoveries occurred without significant
      sequelae. In the remaining 2 cases, the drainage tube was found to be obstructed
      by a blood clot such that the haematoma was unaffected. A traditional craniotomy
      was performed within 8-12 hours, and these 2 patients recovered consciousness
      within the subsequent 6 hours. CONCLUSION: Burr hole evacuation followed by
      drainage under negative pressure is a safe and effective method for emergency
      management of a pure traumatic epidural haematoma. To assure safety patients
      given this procedure should be monitored by daily CT scans. Decompressive
      craniotomy should be performed if consciousness does not improve within several
      hours.

PMID- 16437188
TI  - Molecular phylogeny of VP1, 2A, and 2B genes of echovirus isolates:
      epidemiological linkage and observations on genetic variation.
AB  - Phylogenetic relationships between 37 echovirus clinical isolates, most of them
      originating from an aseptic meningitis outbreak during 2001 in Greece, were
      investigated by RT-PCR and sequencing. The generic primers 292 and 222 were used
      to amplify about 300 bp of the 5' end of VP1 while primers EUG3a, 3b, 3c, and
      EUC2 amplified the entire coding sequence of the 2A and 2B genes. Phylogenetic
      trees were constructed for each genomic region using the clinical isolates'
      sequences and those of the prototype echoviruses in order to investigate the
      correlation of part of VP1 with the serotype as well as the genetic variation of
      the echovirus genome in 2A and 2B. The phylogenetic grouping pattern of the
      clinical isolates revealed that there is a correlation of serotype and genotype
      in the part of VP1 that was investigated, while this pattern is disrupted in the
      adjacent genomic regions that were sequenced. Sequence analysis of the adjacent
      2A and 2B genes provided a different pattern of phylogenetic relationships and
      strong evidence of epidemiological linkage of most of the clinical isolates.

PMID- 16437189
TI  - South Indian men with reduced CAG repeat length in the androgen receptor gene
      have an increased risk of prostate cancer.
AB  - The androgen receptor (AR) gene possesses polymorphic CAG tandem repeats and the
      repeat length has been inversely related to the risk of prostate cancer (PCa).
      The distinct ethnic variation in the CAG repeat length may be correlated to
      differences in PCa risk in different populations. To evaluate the CAG repeat
      length in the AR gene and the implications for PCa, we screened 87 PCa patients
      and 120 control subjects from South India. The mean CAG repeat length in PCa
      patients was significantly smaller than that of controls (17.0 vs 20.7; P <
      0.001). Men with < or = 19 CAG repeats had a significantly increased risk of
      cancer compared to those with >19 CAG repeats (age-adjusted OR = 7.01; 95% CI =
      3.52-13.94; P < 0.001). However, no significant association was observed between
      CAG repeats and age of onset or prostate-specific antigen levels. Although there
      was a trend towards shorter CAG repeat length in high grades of cancer, it was
      not significant (P = 0.085). Thus, our results suggest an association between
      short CAG repeats in the AR gene and PCa risk in South Indian men. Further, we
      propose that CAG repeats could be used as a prognostic marker for PCa diagnosis.

PMID- 16437190
TI  - Serum osteoprotegerin and receptor activator of nuclear factor-kappaB ligand
      (RANKL) concentrations in allogeneic stem cell transplant-recipients: a role in
      bone loss?
AB  - PURPOSE: Osteoporosis is a long-term complication of allogeneic stem cell
      transplantation (SCT). Receptor activator of nuclear factor-kappaB ligand (RANKL)
      increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A
      deficiency of OPG or an excess of RANKL may contribute to post-SCT bone loss.
      METHODS: Serum OPG and soluble RANKL (sRANKL) concentrations were determined in
      30 patients who received calcium, vitamin D and sex steroids--with or without
      pamidronate--prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to
      those in healthy controls. RESULTS: Despite all treatments patients lost bone at
      the hip. At baseline, serum OPG was similar in patients and controls; in the two
      patient groups it increased by 26-27% at 6 months post-SCT (p=0.002-0.028) and
      over the control level (p=0.002). Serum sRANKL concentrations were also similar
      in patients and controls at baseline. In those patients receiving pamidronate
      sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The
      findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in
      28 additional patients who did not receive pamidronate, at a median of 122 days
      after SCT. In this latter group, OPG but not sRANKL concentrations were clearly
      elevated (p<0.001) in comparison to healthy controls. In conclusion, the present
      study fails to support the view that an excess of sRANKL or a deficiency of OPG
      would have a substantial impact on bone loss in SCT-recipients. CONCLUSION: Serum
      sRANKL concentrations may be modulated by bisphosphonates.

PMID- 16437191
TI  - Does an educational leaflet improve self-reported adherence to therapy in
      osteoporosis? The OPTIMA study.
AB  - INTRODUCTION: Adherence to treatment in osteoporosis remains poor. The aim of
      this study was to evaluate the effects of an educational leaflet on adherence to
      medication and to assess the association between adherence and health-related
      quality of life (HRQOL). METHODS: A naturalistic, observational, multi-center,
      prospective study of 12 months' follow-up was performed. Consecutive post
      menopausal women aged 50 years to 86 years starting treatment with raloxifene
      according to daily practice were enrolled from 126 primary care offices in Spain.
      The women were assigned to two study groups. Group A received an educational
      leaflet with general information about osteoporosis; group B followed current
      practice. To assess adherence to medication and HRQOL, the Morisky test and the
      EuroQoL questionnaire were administered. A total of 745 post-menopausal women
      (group A, n=366; group B n=379), with a mean age of 62 years, were included.
      RESULTS: Most patients in both study groups showed high adherence to raloxifene
      at the 3-month visit: 56.3% vs 62.7% for groups A and B, respectively; this
      proportion at the 12-month visit was 47.4% (P=0.15) and 52.5% (P=0.02),
      respectively. At baseline, "pain/discomfort" was the dimension showing the
      highest percentage of women reporting problems: 86.4% vs 83.2% in groups A and B,
      respectively (P=0.22). HRQOL improved in both groups throughout the study, with
      an overall mean increment in the EuroQoL visual analog scale (EQ VAS) of 9.2 at
      12 months (P<0.01). Correlations between adherence and HRQOL were weak. After
      receiving an educational leaflet, young post-menopausal women suffering
      osteoporosis did not show improvement in adherence to therapy. HRQOL improved at
      12-month follow-up under treatment. CONCLUSION: No consistent correlation between
      adherence and HRQOL was found.

PMID- 16437192
TI  - Features of the metabolic syndrome and the risk of non-vertebral fractures: the
      Tromso study.
AB  - INTRODUCTION: We wanted to examine whether the features of the metabolic syndrome
      carried an increased risk of non-vertebral fracture. METHODS: This is a
      population-based, 6-year follow-up of 27,159 subjects from the municipality of
      Tromso, followed from 1994 until 2001. Age range was 25-98 years. Non-fasting
      serum levels of high-density lipoprotein (HDL), triglycerides and glucose, blood
      pressure (BP), weight and height were measured at baseline. All non-vertebral
      fractures were registered by computerised search in radiographic archives.
      RESULTS: A total of 1,249 non-vertebral fractures were registered. Increasing
      number of metabolic syndrome features was associated with significantly reduced
      fracture risk in both men and women, p= 0.004 and p<0.0001, respectively. High BP
      was protective against fracture in men [relative risk (RR) 0.89; 95% confidence
      interval (CI) 0.8-0.99)] while increased body mass index (BMI) was protective in
      women (RR 0.91; 95% CI 0.84-0.98). Increasing non-fasting serum levels of HDL
      increased fracture risk in women (RR 1.12; 95% CI 1.05-1.21). BMI modified the
      effect of HDL in men. Accordingly, high HDL increased fracture risk in men with
      high BMI (RR 1.51; 95% CI 1.2-1.9). CONCLUSIONS: Increasing burden of metabolic
      syndrome features protects against non-vertebral fractures. Reduced non-vertebral
      fracture risk was associated with high BP in men and increased body mass in
      women. Lower non-fasting serum levels of HDL protect against fractures in women
      and obese men.

PMID- 16437193
TI  - Body composition and vertebral fracture risk in female patients treated with
      glucocorticoid.
AB  - INTRODUCTION: Glucocorticoid (GC) causes bone loss and an increase in bone
      fragility. However, fracture risk was found to be only partly explained by bone
      mineral density in GC-treated patients (GC patients). Although GC causes a change
      in the distribution of fat in the body, the relationship between body composition
      and fracture risk in GC patients remains unknown. METHODS: The present study
      examined the relationship between the presence or absence of vertebral fractures
      and various indices, including body composition, in 92 premenopausal GC patients,
      122 postmenopausal GC patients and 122 postmenopausal age-matched control
      subjects. Dual-energy X-ray absorptiometry was employed to analyze body
      composition. RESULTS: Percentage lean body mass (LBM), % fat and % trunk fat were
      not significantly different between postmenopausal GC patients and the control
      women. When groups with and without vertebral fractures were compared, % LBM and
      % fat were significantly higher and lower in groups with vertebral fractures,
      respectively, in postmenopausal GC patients, but not in the postmenopausal
      control women, although % trunk fat was not significantly different between
      groups with and without vertebral fractures. Femoral neck BMD was negatively
      correlated with % LBM and positively correlated with % fat. In premenopausal GC
      patients, % trunk fat was significantly higher in the fracture group, although %
      LBM and % fat were not significantly different between groups with and without
      vertebral fractures. CONCLUSION: The present study revealed that body composition
      is related to vertebral fracture risk in GC-treated patients. Lower % fat can be
      included in the determination of vertebral fractures in postmenopausal GC-treated
      patients. The influence of body composition on vertebral fracture risk may be
      different between the pre- and postmenopausal state in GC patients.

PMID- 16437194
TI  - Age-related changes in trabecular bone microstructures: global and local
      morphometry.
AB  - INTRODUCTION: A recently developed method allows investigating trabecular bone on
      an elemental (rod/plate) level. With this method, it is possible to measure local
      morphometric parameters such as thickness or orientation directly on the
      extracted rods and plates. Age-related changes of trabecular microarchitecture
      can thus be investigated on an elemental level, which may help to improve the
      understanding of age-related bone failure mechanism as well as the effect of
      pharmaceutical intervention in the prevention of such fractures. METHODS:
      Autopsies from femoral heads (FH) and lumbar spine (LS) were analyzed by global
      morphometry. Additionally, the trabecular structures were decomposed into rods
      and plates for the analysis with local morphometry. These morphometric indices
      were related to age using an analysis of covariance to test for gender
      differences and linearity with age. RESULTS: In this study, age-related changes
      showed no gender but site differences. In LS, rods were thinned in aging and
      finally vanish from the structure, causing a transformation of the trabecular
      bone structure to longer and, on average, thicker rods. In FH, changes were
      expressed by a simultaneous thinning and loss of interconnecting trabeculae and
      perforation of plates leading to new plates and rods. Results were mostly in
      agreement with earlier findings using descriptive analysis of the aging process.
      CONCLUSION: Here we present for the first time preliminary quantitative evidence
      of changes in the local microstructure, i.e., individual rods and plates.
      Nevertheless, the number of samples was too small to make for ready conclusions.
      We conclude that the combination of local and global morphometry is a useful
      method for a detailed and quantitative description of age-related changes in bone
      microstructure.

PMID- 16437195
TI  - Detection of osteoporotic vertebral fractures using multidetector CT.
AB  - INTRODUCTION: Goals were to compare the performance of lateral radiographs and
      sagittal reformations (SR) of axial computed tomography (CT) datasets in
      identification of osteoporotic vertebral fractures and to assess for optimal
      slice thickness in axial CT datasets needed for reliable classification of these
      fractures. METHODS: Sixty-five vertebrae were harvested from 21 human cadaver
      spines and examined with a 64-row multidetector CT scanner. Axial images were
      acquired with a slice thickness of 0.6, 1, 2, 3 and 5 mm and SR were obtained
      using these datasets. In addition, specimens were radiographed in antero
      posterior and lateral orientation. Vertebrae visualized in the different image
      datasets were separately graded by four radiologists according to the spinal
      fracture index (SFI) classification. Fracture status determined in a consensus
      reading of interactive reformations of the 0.6-mm CT dataset in all three
      dimensions served as a standard of reference in combination with pathological
      examinations. RESULTS: The average agreement for the 0.6-mm SR obtained between
      each radiologist and standard of reference for the grading of the fractures was
      very good (kappa=0.81). It was good for the 1-, 2- and 3-mm SR (kappa=0.70, 0.69
      and 0.64), but only moderate for the radiographs (kappa=0.52), and fair for the 5
      mm SR (kappa=0.33). When focusing only on detection of fractures, independent of
      the grading, all kappa values improved by about 0.15, resulting in excellent
      values for the 0.6-mm through 3-mm SR (0.95<kappa<0.79) and good values for the
      radiographs (kappa=0.72). Ninety-five percent of the fractures could be
      identified using the 1-mm SR, but 18% of the fractures were missed on the
      radiographs. CONCLUSIONS: Sagittal CT reformations could more accurately assess
      vertebral fractures than standard radiographs. But for reliable detection of
      these fractures, SR derived from axial images with a slice thickness of 3 mm or
      less are required. The thinnest available axial slice thickness performed best in
      fracture grading.

PMID- 16437196
TI  - Pneumococcus pneumoniae infection and Guillain-Barre syndrome: fortuitous or
      specific association?

PMID- 16437197
TI  - Elevation in interleukin 13 levels in patients diagnosed with systemic
      inflammatory response syndrome.
AB  - OBJECTIVE: To examine plasma levels and circadian rhythm of interleukin 13 (IL
      13), tumour necrosis factor (TNF) alpha and total serum cortisol in the systemic
      inflammatory response syndrome (SIRS). DESIGN AND SETTING: Prospective
      observational study in a 12-bed medical-surgical ICU of a 500-bed university
      hospital. PATIENTS: Ten patients with SIRS and eight controls. MEASUREMENTS:
      Arterial blood was sampled hourly for 24 h for measurement of plasma IL-13, TNF-
      alpha, cortisol and white blood cell count (WCC) differential within 24 h of
      development of SIRS. RESULTS: There were significantly higher plasma IL-13 levels
      in SIRS patients than in controls (1282 vs. 713 pg/ml). IL-13 was significantly
      higher in patients with a diagnosis of sepsis than in those with non-infectious
      causes of SIRS (2080 vs. 515 pg/ml). In SIRS the elevation in IL-13 was
      associated with higher TNF-alpha and reduced WCC. A circadian rhythm was observed
      in plasma IL-13 secretion. No distinct circadian rhythm was noted for TNF- alpha,
      and the normal circadian rhythm of serum cortisol was lost. CONCLUSIONS: The anti
      inflammatory cytokine IL-13 is elevated in early SIRS. Its plasma level exhibits
      a circadian rhythm and may be modulated in part by TNF-alpha. SIRS patients have
      disruption of the normal circadian rhythm of serum cortisol.

PMID- 16437198
TI  - Supply and demand of organs for donation.

PMID- 16437199
TI  - Temporomandibular disorders seen in rheumatology practices: A review.
AB  - Temporomandibular disorders are recognized as the most common nontooth-related
      chronic orofacial pain conditions. This article reviews the recent
      temporomandibular disorders literature and summarizes the temporomandibular
      disorders seen in rheumatology practices. Arthritis is a common condition
      affecting the temporomandibular joint. Although degenerative and rheumatoid
      arthritis are the most frequently encountered infectious arthritis, metabolic
      arthritis, spondyloarthropathies and the traumatic arthritis have also been
      reported. Distinguishing between different temporomandibular disorders is as
      important as the clinical course, long-term prognosis, and therapy. Diagnostic
      criteria are generally based on signs and symptoms of the patient. The American
      Academy of Orofacial Pain established the first well-defined diagnostic
      classification. In addition, Research Diagnostic Criteria for Temporomandibular
      Disorders have been developed using similar classification. In the treatment of
      temporomandibular disorders, conservative and noninvasive treatments are endorsed
      for the initial care of nearly all TMD patients because the majority of patients
      with TMD achieve good relief of symptoms with conservative treatment.

PMID- 16437200
TI  - Celecoxib inhibits nitric oxide production in chondrocytes of ligament-damaged
      osteoarthritic rat joints.
AB  - The purpose of this study was to demonstrate the direct effects of celecoxib, one
      of the selective cyclo-oxygenase (COX)-2 inhibitors, on nitric oxide (NO) and
      prostaglandinE2 (PGE2) synthesis in cultured osteoarthritic chondrocyte comparing
      with those of indomethacin. Articular chondrocytes were isolated from rat
      osteoarthritic knee joint with damaged anterior cruciate ligament and also from
      the sham knee joint. Chondrocytes were preincubated with or without IL-1 alpha,
      and were exposed to celecoxib, indomethacin (non-selective COX inhibitor), or
      nothing. The amounts of NO and PGE2 in culture supernatants of chondrocytes were
      measured by EIA or the Griess reaction. In a series of experiments preincubated
      with or without IL-1 alpha and exposed to nothing, PGE2 and NO levels were
      significantly higher in osteoarthritic chondrocytes than in sham chondrocytes.
      Celecoxib and indomethacin inhibited the increase of PGE2 in osteoarthritic
      chondrocytes. Celecoxib inhibited and indomethacin did not inhibit the increase
      of NO levels in osteoarthritic chondrocytes.

PMID- 16437201
TI  - Use of fluorescence spectroscopy to differentiate yeast and bacterial cells.
AB  - This study focuses on the characterization of bacterial and yeast species through
      their autofluorescence spectra. Lactic acid bacteria (Lactobacillus sp.), and
      yeast (Saccharomyces sp.) were cultured under controlled conditions and studied
      for variations in their autofluorescence, particularly in the area representative
      of tryptophan residues of proteins. The emission and excitation spectra clearly
      reveal that bacterial and yeast species can be differentiated by their intrinsic
      fluorescence with UV excitation. The possibility of differentiation between
      different strains of Saccharomyces yeast was also studied, with clear differences
      observed for selected strains. The study shows that fluorescence can be
      successfully used to differentiate between yeast and bacteria and between
      different yeast species, through the identification of spectroscopic
      fingerprints, without the need for fluorescent staining.

PMID- 16437203
TI  - Evaluation of femtosecond LIBS for spectrochemical microanalysis of aluminium
      alloys.
AB  - The analytical performance of femtosecond laser-induced breakdown spectroscopy
      (LIBS) for elemental microanalysis of aluminium alloys and for mapping
      precipitate distribution on the sample surface has been studied in detail. A Ti
      sapphire laser system producing pulses of 130 fs at 800 nm was used to generate
      the laser-induced plasma. Multi-element microanalysis of commercially available
      aluminium alloys was performed in air at atmospheric pressure. Crater
      characteristics such as diameter and crater morphology were characterized by
      optical and scanning-electron microscopy. Scaling of plasma emission and limit of
      detection as a function of laser pulse energy was also investigated. Current
      experimental results are presented and are compared with previous nanosecond
      microLIBS measurements.

PMID- 16437202
TI  - High-level production of bioactive human beta-defensin-4 in Escherichia coli by
      soluble fusion expression.
AB  - Human beta-defensin-4 (hBD4) is a cationic 50-amino acid antimicrobial peptide
      with three conserved cysteine disulfide bonds. It exhibits a broad antimicrobial
      spectrum. This study describes the synthesis of hBD4 gene, the heterologous
      fusion expression of the peptide in Escherichia coli, and the bioactive assay of
      released hBD4. A PCR-based gene SOEing (splicing by overlap extension) synthesis
      method was used in the synthesis of the hBD4 gene with optimized codons. By
      constructing the expression plasmid (pET32-smhBD4), high concentration of soluble
      hBD4 fusion protein (1.9 g/l) can be obtained in E. coli. Further optimization
      studies showed that the expression system was very efficient to produce soluble
      target protein, and the solubility of the target protein could attain more than
      99% even when the culture temperature was as high as 37 degrees C. The highest
      productivity (2.68 g/l) of the hBD4 fusion protein was achieved by cultivating
      the E. coli (pET32-smhBD4) in MBL medium at 34 degrees C, inducing the culture at
      the mid-exponential phase with 0.4-mM isopropyl beta-D-galactopyranoside (IPTG),
      and collecting the broth after 6-h expression. The soluble target protein
      accounted for 64.6% of the total soluble proteins, and the mature hBD4 expression
      level was stoichiometrically estimated to be 0.689 g/l. This fusion protein was
      then purified and cleaved to get the mature hBD4 peptide that showed
      antimicrobial activity against E. coli and Pseudomonas aeruginosa.

PMID- 16437204
TI  - Unusual CT sign of colonic duplication in a child.

PMID- 16437205
TI  - Monozygotic twins with discordant intestinal rotation.
AB  - Previous case reports have suggested a strong concordance of intestinal
      malrotation among identical twins. This has led to the recommendation that the
      asymptomatic twin undergo screening when malrotation is discovered in the
      identical sibling. We present a case of monozygotic twins in which one twin
      presented with intestinal malrotation with midgut volvulus while the other twin
      was found to have normal gastrointestinal anatomy.

PMID- 16437206
TI  - Heterogeneity of neuromuscular junctions in striated muscle of human esophagus
      demonstrated by triple staining for the vesicular acetylcholine transporter,
      alpha-bungarotoxin, and acetylcholinesterase.
AB  - During studies on enteric co-innervation in the human esophagus, we found that
      not all acetylcholinesterase (AChE)-positive motor endplates stained for alpha
      bungarotoxin (alpha-BT) and the vesicular acetylcholine transporter (VAChT),
      respectively. Therefore, we probed for differences in neuromuscular junctions in
      human esophagus by using triple staining for VAChT, alpha-BT, and AChE followed
      by qualitative and quantitative analysis. To exclude that the results were caused
      by processing artifacts, we additionally examined the influence of a number of
      factors including post-mortem changes and the type and duration of fixation on
      the staining results. Four types of neuromuscular junction could be distinguished
      in human esophagus: type I with VAChT-positive and type II with VAChT-negative
      nerve terminals on a alpha-BT-positive and AChE-positive endplate area, type III
      with VAChT-positive nerve terminals on a alpha-BT-negative but AChE-positive
      endplate area, and type IV with VAChT-negative nerve terminals on a alpha-BT
      negative but AChE-positive endplate area. On average, 32% of evaluated AChE
      positive motor endplates were type I, 6% type II, 24% type III, and 38% type IV.
      Based on these results, we suggest that, in human esophagus, (1) the most
      reliable method for staining motor endplates is presently AChE histochemistry,
      (2) alpha-BT-sensitive and alpha-BT-resistant nicotinic acetylcholine receptors
      exist in neuromuscular junctions, and (3) different types of VAChT or transport
      mechanisms for acetylcholine probably exist in neuromuscular junctions.

PMID- 16437207
TI  - Expression of prostaglandin E2 receptor subtypes, EP2 and EP4, in the rat
      hippocampus after cerebral ischemia and ischemic tolerance.
AB  - We investigated the distribution and time course of expression of two subtypes of
      prostaglandin E(2) (PGE(2)) receptors, EP2 and EP4, in a rat model of cerebral
      ischemia and ischemic tolerance. Adult male Sprague-Dawley rats were subjected to
      either lethal global ischemia (10 min) with or without sublethal ischemic
      preconditioning (3 min), or ischemia only (3 min). A short 3-min cerebral
      ischemia and a 3-min ischemia followed by a second lethal ischemia enhanced the
      expression of EP2 and EP4 receptors in CA1 pyramidal neurons of the hippocampus.
      In tolerance-acquired CA1 neurons, the immunoreactivities of EP2 and EP4 were
      upregulated after 4 h and 12 h, respectively. The immunoreactivities were most
      prominent at 3 days and were sustained for at least 14 days, consistent with
      results of immunoblotting experiments. However, immunoreactivities for these
      PGE(2) receptors increased in reactive glial cells in the vulnerable CA1 and
      hilar regions of rats subjected to lethal ischemia without ischemic
      preconditioning. Most of the EP2 immunoreactivity occurred in microglial cells
      and some astrocytes, whereas increased immunoreactivity for EP4 was found only in
      astrocytes. These data suggest that ischemia and the induction of ischemia
      tolerance have different regulatory effects on the expression of EP2 and EP4
      receptors. Moreover, PGE(2) may exert its unique pathophysiological functions in
      relation to delayed neuronal death and ischemic tolerance induction in the rat
      hippocampus via specific PGE(2) receptors.

PMID- 16437208
TI  - Soft-tissue malignant fibrous histiocytoma (high-grade undifferentiated
      pleomorphic sarcoma) arising in a desmoid tumor in a patient with Milroy's
      disease.

PMID- 16437209
TI  - A study on chirality in biomolecules: the effect of the exchange of L: amino
      acids to D: ones in Sso7d ribonuclease.
AB  - In this work, the conformational behavior of ribonuclease Sso7d is studied as a
      function of chirality of its constituting amino acids. Both optimized structures
      (using molecular mechanics with the CHARMM force field) and dynamic behavior
      (obtained by molecular dynamic simulations) are compared.

PMID- 16437210
TI  - Serum biochemical evaluation of patients with functional pouches ten to 20 years
      after restorative proctocolectomy.
AB  - BACKGROUND: Restorative proctocolectomy with an ileal pouch-anal anastomosis is a
      surgical treatment of choice for ulcerative colitis and familial adenomatous
      polyposis (FAP). Pouchitis is a significant enigmatic morbidity. In the long
      term, these patients, we anticipated, would experience biochemical profiling
      alterations after years of retaining functionally acceptable pouches. This pilot
      study was aimed at assessing results of essential biochemical variables more than
      10 years after surgery. METHODS: The investigation was carried out in 91
      patients; 39 were women. Eight-eight had ulcerative colitis, while three had
      FAPs. The hand-sewn ileal reservoirs after mucoso-proctocolectomy were 66 S and
      25 J. The analyses were compared short-term vs long-term. Patients were
      investigated and were their own control. RESULTS: Long-term, incidence of acute
      and chronic pouchitis was 2 and 13%. Eleven and 4% of patients had
      hypomagnesaemia and hypocalcaemia. Mean levels were significantly enhanced
      (p<0.01 and p<0.0002). Hypomagnesaemia corresponded to episodes of pouchitis and
      was corrected with oral magnesium and antibiotics. Hypoferric anaemia was
      diagnosed in 7% and treated with oral iron tablets. Chronic pouchitis and
      recurrent pouch mucosa bleeding were the cause. Hypohemoglobinemia and
      hypocyanocobalaminemia were noted in 5% and 5%, respectively. Erythrocyte
      sedimentation rate and white blood cells were supra-normal in 13 and 10%, which
      corresponded with pouchitis. A significant (p<0.03) steady rise of mean serum
      immunoglobulin G without correlation to pouchitis was noted. CONCLUSION: Long
      term functional results did not deteriorate. Pouchitis was a significant
      enigmatic morbidity. Severe or chronic pouchitis complicated hypoferric and
      vitamin B(12) anemia and hypomagnesaemia.

PMID- 16437211
TI  - Resection and primary anastomosis in acute complicated diverticulitis, a
      systematic review of the literature.
AB  - OBJECTIVE: To determine the safety and feasibility of primary resection and
      anastomosis with or without a diverting stoma, as compared to Hartmann's
      procedure, for patients with acute complicated sigmoid diverticulitis. SEARCH
      STRATEGY: MEDLINE was searched for studies and trials conducted between 1966 and
      December 2003. This search revealed trials comparing primary resection and
      anastomosis to Hartmann's procedure. The term "diverticulitis, colonic" with the
      sub-heading "surgery" was used and the search was limited to human studies and
      clinical trials. Additional studies were found using the MeSH terms: "surgical
      procedures, operative", "surgical anastomosis", and "Hartmann procedure",
      combined with the term "diverticulitis, colonic". The author also searched EMBASE
      and the Cochrane database for clinical trials using similar terminology. No
      language restrictions were applied. RESULTS: Eighteen studies met the inclusion
      criteria and reported 884 patients with acute complicated diverticulitis. None of
      these studies were randomised; it is likely that there was a significant degree
      of selection bias. No significant differences were found between primary
      resection with anastomosis and Hartmann's procedure with respect to mortality,
      morbidity, sepsis, wound complications and duration of procedure and anti-biotic
      treatment. Some studies found that primary anastomosis and a protecting stoma,
      with or without intra-operative colonic lavage, have more favourable results than
      Hartmann's procedure. CONCLUSIONS: This review suggests that surgical resection
      and primary anastomosis in acute diverticulitis with peritonitis compares
      favourably with Hartmann's procedure in terms of peri-operative complications.
      The need for revision of Hartmann's procedure could be subsequently avoided. Some
      articles showed that patients with severe peritonitis, who had a diverting stoma,
      in the setting of resection and primary anastomosis, had the lowest complication
      rate. However, the quality of these studies was poor with the presence of
      selection bias.

PMID- 16437212
TI  - Gastrointestinal cancer web sites: how do they address patients' concerns?
AB  - BACKGROUND: We studied the quality of web sites containing information on
      gastrointestinal cancer, focusing on the way these web sites dealt with the
      special concerns of these patients. MATERIALS AND METHODS: Searching the Internet
      for German-language gastroenterological cancer web sites, we collected 9,947 web
      pages from 14 search engines. Evaluation was done with a 36-item questionnaire.
      Information quality, availability of the web sites, and web site attributes
      considering patients' concerns and potential embarrassment were analyzed using a
      scoring system. RESULTS: Belonging to 165 web sites, 1,763 of 9,947 (17.7%) web
      pages found by search engines provided relevant information. Five hundred forty
      seven (5.5%) hits were partly relevant, and 7,637 (76.8%) were irrelevant or not
      available. Most web sites reported about surgery (92.1%), chemotherapy (88.5%),
      and radiotherapy (73.9%). Of the web sites, 46.7% (n=77), 34.6% (n=57), and 21.8%
      (n=36) gave information about the author(s) itself, their qualifications, and
      references of their information, respectively. Search engines ranked web sites
      giving no information on evidence-based medicine higher than other web sites,
      whereas web sites providing this information accurately showed higher link
      popularities. Patients' concerns and potential embarrassment were best addressed
      by gastrointestinal web sites initiated by private individuals or web sites
      directed to both a patient and physician audience. CONCLUSIONS: With regard to
      gastrointestinal cancer web sites, many search engines may be ineffective, and
      patient emotional needs and concerns are often disregarded. Also, physicians
      should guide their patients through the Internet to find high-quality information
      and use link-popularity-based search strategies.

PMID- 16437213
TI  - An improved Tet-On regulatable FasL-adenovirus vector system for lung cancer
      therapy.
AB  - Gene therapy is a new therapeutic approach for the treatment of human cancers.
      Gene expression systems that can be regulated by drugs have been developed to
      improve the safety and efficacy of therapeutic transgene delivery. One of the
      most promising systems is the tetracycline (Tet)-responsive system in the Tet-On
      configuration. A major problem of the Tet-On system if used in viral vectors is
      the high basal activity of the Tet response element (TRE) promoter leading to
      leaky expression of transgenes under uninduced conditions. We therefore evaluated
      novel TRE promoters for controlling gene expression in an adenovirus vector (AdV)
      Tet-On system and further investigated them for expression of the pro-apoptotic
      CD95/Fas ligand (FasL) in human epithelial carcinoma cell line (HeLa) and lung
      cancer cells. Plasmid-based reporter gene assays showed that modifications within
      the tetO (7) and minimal immediate early cytomegalovirus promoter (CMV)(min)
      sequence of the TRE promoter reduced its leakiness and led to a markedly improved
      regulatability by doxycycline. Among several TRE promoters tested, a new
      construct (TRE-Tight1) containing modifications of both the tetO (7) sequence and
      the CMV(min) showed 11-fold reduced leakiness and 1.5-fold increased absolute
      transgene expression levels after induction, as compared to the original TRE.
      Under induced conditions, a TRE-Tight1 promoter-dependent AdV expressing the pro
      apoptotic CD95L/FasL induced apoptosis and cell lysis in HeLa cells as
      efficiently as an AdV containing the original TRE promoter. In contrast to the
      latter, however, the vector with the modified TRE promoter left cells totally
      unaffected in the absence of the inducer. Stringently regulated induction of
      apoptosis and cell death by TRE-Tight1-AdV was also demonstrated in three human
      lung cancer cell lines. These data show that the novel TRE-Tight1 promoter has a
      high potential for closely controlled and efficient expression of cytotoxic genes
      in AdV-based anti-cancer approaches.

PMID- 16437214
TI  - Isoform-specific silencing of the Livin gene by RNA interference defines Livin
      beta as key mediator of apoptosis inhibition in HeLa cells.
AB  - Livin (alternatively called ML-IAP or KIAP) is a cancer-associated member of the
      antiapoptotic inhibitor of apoptosis protein family. Two splicing variants of
      Livin, designated Livin alpha and Livin beta, have been identified. The
      significance of these isoforms for Livin-mediated apoptosis inhibition is largely
      unclear. Using an isoform-specific RNA interference (RNAi) strategy, we silenced
      endogenous Livin expression in HeLa cells. We found that the targeted inhibition
      of Livin beta, but not of Livin alpha, blocked the growth of HeLa cells in
      clonogenic survival assays. In addition, silencing of Livin beta, but not of
      Livin alpha, sensitized HeLa cells to different proapoptotic stimuli such as UV
      irradiation, tumor necrosis factor alpha, or etoposide. These events were linked
      to activation of caspase-3 and increased poly(ADP-ribose) polymerase cleavage,
      specifically upon silencing of Livin beta. The proapoptotic sensitization of HeLa
      cells upon RNAi-mediated silencing of the endogenous livin gene was specifically
      reverted by ectopic expression of Livin beta but not of Livin alpha. We conclude
      that the Livin beta isoform plays the key role for the antiapoptotic protection
      of HeLa cells by the livin gene. Our results show that the Livin isoforms can
      strongly differ in their functional significance for the antiapoptotic resistance
      of tumor cells. Studies evaluating Livin as a novel diagnostic and prognostic
      tumor marker should benefit from isoform-specific expression analyses.

PMID- 16437215
TI  - [The "Muenster classification" of high frequency hearing loss following cisplatin
      chemotherapy].
AB  - BACKGROUND: Slight high frequency hearing loss following cisplatin chemotherapy
      can be proof of an ototoxic effect even when hearing ability is not yet
      clinically affected. To answer scientific questions, such as the relationship
      between cisplatin ototoxicity and drug regime or individual tolerance, early
      detection of ototoxicity and a classification relating to intensity and the
      affected frequencies are required. A search for relevant literature resulted the
      WHO-classification (1991) describing clinically relevant hearing loss and two
      high frequency hearing loss classifications published by Khan et al. (1982) and
      Brock et al. (1991). Their application is compared to a new, proprietary
      classification. PATIENTS AND METHODS: 55 patients (32 boys, 23 girls) undergoing
      cisplatin chemotherapy at Muenster University Hospital from 1999 to 2004
      underwent audiometric tests in our department. From this data we developed a
      grading system, that was based on the WHO classification, but paid special
      attention to early ototoxic effects, to intensity of hearing loss and to the
      frequencies affected: Grade 0 (normal hearing) includes hearing loss of not more
      than 10 dB in all frequencies. Grade 1 (beginning hearing loss) encompasses > 10
      dB up to 20 dB in at least one frequency or tinnitus. Grade 2 (moderate
      impairment) describes hearing loss > or = 4 kHz and differentiates 2a (> 20 to 40
      dB), 2b (> 40 to 60 dB) and 2c (> 60 dB). Hearing loss < 4 kHz > 20 dB in grade 3
      (severe impairment, hearing aids needed) is further classified according to grade
      2 in a, b and c. Grade 4 (loss of function) finally describes average hearing
      loss < 4 kHz of at least 80 dB. This classification is compared to the two high
      frequency hearing loss classifications (Khan et al. and Brock et al.). RESULTS:
      The Muenster classification, compared to Khan et al. and Brock et al.,
      demonstrated the best results in the early detection of hearing loss: All
      children with hearing loss of at least 20 dB after therapy had already shown
      pathological audiograms during treatment, when those audiograms were assessed by
      our classification. All children whose audiograms were flagged as pathological by
      our classification finally developed hearing loss. In terms of the prediction of
      hearing loss, our classification evaluated processing audiograms with a
      sensitivity, specificity and efficiency of 1.0. Progressive hearing loss was
      detected in 45 patients (Khan et al. 30, Brock et al. 38). Therefore our
      classification showed a better suitability for monitoring hearing loss than the
      other classifications. CONCLUSION: The Muenster classification is a suitable new
      basis for scientific questions concerning cisplatin ototoxicity. It detects
      hearing loss earlier and maps progression of hearing loss more precisely than the
      existing high frequency classifications (Khan et al. and Brock et al.).

PMID- 16437216
TI  - [Coblation tonsillectomy. Results of a pilot study].
AB  - BACKGROUND: The introduction of coblation tonsillectomy (CTE) may contribute to
      reduce the postoperative morbidity in terms of pain, delayed oral intake and
      bleeding. METHODS: A prospective pilot study was undertaken to evaluate the
      clinical course by inpatient observation (5 days) and telephone contact 6 months
      after CTE. The data from 61 patients (aged 44 months-69 years) were analyzed. The
      patients were grouped into those with surgical care of bleeding (A), non-surgical
      care of bleeding (B), and no bleeding event (C). RESULTS: The study was
      terminated early due to major bleeding complications in seven patients (A).
      Fifteen patients experienced minor (B) and 41 no (C) bleeding episodes. In the
      interview, 29 patients identified pain, lasting 16.7 (A), 11.6 (B) and 11 (C)
      days, as the most significant complication of surgery. CONCLUSIONS: The
      introduction of CTE was followed by a dramatic increase in major bleeding
      complications, including late bleeding episodes. Pain following tonsillectomy
      remains a problem to be solved by further techniques. We will continue to perform
      the cold dissection technique.

PMID- 16437217
TI  - [Documentation of endonasal changes in blood volume using optical rhinometry].
AB  - BACKGROUND: In optical rhinometry, the nose is transilluminated with light and
      the light absorption by the nasal tissue is measured continuously. Using this
      method, a real time documentation of changes in nasal blood volume is possible.
      The method has been evaluated using the nasal allergen provocation test. In this
      study, the ability of optical rhinometry to detect changes in the nasal blood
      volume due to various posture changes is examined. METHODS: Optical rhinometry
      was tested on ten healthy probands, with several examinations being performed on
      each. RESULTS: By bending the neck, lying down or stopping breathing, stronger
      light extinction was found. Standing up quickly caused a sudden but short
      decrease in light extinction. A small amount of exercise, such as making a fist
      several times, decreased light extinction. Harder exercise on an ergometer led to
      a stronger decrease in light extinction. In the Valsalva maneuver, an increase in
      light extinction for the duration of the maneuver was observed. Changes in
      breathing through the nose or mouth or counting from 1 to 100 had no influence.
      CONCLUSIONS: Using the new method of optical rhinometry, it is possible to detect
      changes in endonasal blood volume caused by changes of intrathoracic pressure,
      changes in posture or physical exercise, non-invasively and in real time. This
      technique can therefore be used for further research on the regulation of the
      nasal blood flow.

PMID- 16437218
TI  - Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic
      neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.
AB  - PURPOSE: The purpose of the study was to evaluate the pharmacokinetics of (68)Ga
      DOTATOC in order to ascertain which parameters have the greatest impact on the
      global DOTATOC standardised uptake value (SUV), defined as the mean SUV of the
      last frame of the dynamic study 55-60 min p.i. METHODS: Twenty-two patients with
      74 metastatic lesions were examined with dynamic (68)Ga-DOTATOC PET studies.
      Standardised uptake values (SUVs) were calculated for all frames following the
      injection of the tracer. We defined global SUV as the mean SUV of the last frame
      (frame duration 5 min) of the dynamic study 55-60 min p.i. A two-tissue
      compartment model with a blood compartment was used for the evaluation of the
      rate constants k (1) (receptor binding), k (2) (displacement from the receptor),
      k (3) (cellular internalisation), k (4) (cellular externalisation) and fractional
      blood volume (V(b)). Furthermore, a non-compartmental model was applied for
      calculation of the fractal dimension (FD) of the time-activity curves based on
      the box counting procedure. RESULTS: Qualitative analysis revealed increased
      uptake of (68)Ga-DOTATOC in 21/22 patients and in 72/74 lesions. The SUV for
      (68)Ga-DOTATOC was highly variable, with a range from 0.877 to 28.07 (mean 8.73).
      The highest uptake was measured in a patient with a NET of the pancreas and the
      lowest in a patient with a medullary thyroid carcinoma (MEN II). The quantitative
      evaluation based on the compartmental analysis revealed high receptor binding (k
      (1)) and internalisation (k (3)) for (68)Ga-DOTATOC, and low cellular
      externalisation (k (4)) as well as a relatively low fractional blood volume
      (V(b)). The FD values varied from 1.10 to 1.45, with a mean of 1.33. No
      significant linear correlation was found for k (1) and k (3). A low, linear
      correlation was noted for k (1) and V(b) (r=0.25,p=0.03), and there was a
      significant non-linear correlation between SUV and FD (r=0.74, p<0.001). Best
      subset analysis demonstrated that k (1) had the greatest impact on the global
      SUV, followed by V(b) and k (3). CONCLUSION: DOTATOC uptake in NETs is mainly
      dependent on k (1) (receptor binding) and V(b) (fractional blood volume).
      Pharmacokinetic data analysis can help to separate blood background activity
      (V(b)) from the receptor binding (k (1)), which may help to optimise planning of
      (90)Y-DOTATOC therapy.

PMID- 16437219
TI  - Acute bacterial prostatitis: two different sub-categories according to a previous
      manipulation of the lower urinary tract.
AB  - Acute bacterial prostatitis (ABP) (NIH Category I), has not undergone any
      modification in the update of prostatitis classification. ABP was diagnosed in
      614 patients in our centre over 9 years (1993-2001). We analyse the clinical
      pattern of ABP and the role of bladder outlet obstruction in its etiology, as
      well as whether two different ABP sub-categories could be defined as a function
      of a history of previous manipulation of the lower urinary tract. The results of
      the study show that the clinical pattern of a patient suffering from ABP does not
      differ from the statements of previous publications. On the other hand, patients
      with ABP have been shown to present with no bladder outlet obstruction. Finally,
      this study has disclosed the fact that the cases of ABP elicited by previous
      manipulation of the lower urinary tract (10%) show a different pattern from those
      cases where no previous manipulation has occurred (90%). The patients with ABP
      secondary to manipulation are older, have a higher risk of prostate abscess and
      higher frequency of multiple infections and also infections by pathogens other
      than Escherichia coli. Due to all of these reasons, it would be advisable to
      subdivide category I within the classification of prostatitis.

PMID- 16437220
TI  - Comparisons of physiological and perceptual responses in healthy men and women
      during standardized arm cranking and task-specific pushing-pulling.
AB  - OBJECTIVE: Peak cardiorespiratory, metabolic, and perceptual responses in healthy
      men (n=11) and women (n=11) were compared during two different upper body
      exercise modes: standardized arm cranking and task-specific pushing-pulling.
      METHODS: Each subject completed to volitional exhaustion both an incremental arm
      cranking and a pushing-pulling exercise continuously, in a random order, on two
      separate days. Physiological responses were monitored using an automated
      metabolic cart and a heart rate monitor, and the rating of perceived exertion was
      obtained using a 15-point Borg Scale. RESULTS: Peak oxygen uptake, oxygen pulse,
      respiratory exchange ratio, and ventilation rate were higher and total exercise
      time to exhaustion was lower during arm cranking compared to pushing-pulling
      (P<0.05). However, heart rate was similar between exercise modes (P>0.05). Men
      showed greater physiological responses (absolute oxygen uptake, oxygen pulse, and
      ventilation rate) and longer exercise time to exhaustion than women (P<0.05).
      Power output during arm cranking was higher (by 79%) than pushing-pulling
      (P<0.01), with men demonstrating 30% greater values during both exercise modes
      (P<0.01). The lower power output generated during pushing-pulling resulted in a
      greater ratio of peak oxygen uptake to power output (by 72%; P<0.05).
      Interestingly, although power output and oxygen uptake were lower at the maximal
      workload, perceived exertion was higher (by 5%) during pushing-pulling (P<0.05).
      CONCLUSIONS: Based on the physiological differences, pushing-pulling is found to
      be metabolically less efficient than arm cranking. However, greater ratings of
      perceived exertion during pushing-pulling implies that the perception of effort
      can also be influenced by a low intensity task, such as pushing-pulling, if
      performed for a prolonged period. Occupational health professionals should be
      aware of the limitations of utilizing physiological and perceptual responses
      obtained only from standardized ergometric protocols in predicting the workers'
      performance effectiveness.

PMID- 16437221
TI  - Validation of a self-administered questionnaire for assessing exposure to back
      pain mechanical risk factors.
AB  - OBJECTIVE: To validate a self-administered questionnaire assessing exposure to
      mechanical risk factors, developed for a cohort study aiming at assessing the
      influence of physical and psycho-social factors on the incidence of low back pain
      (LBP). METHODS: The study first involved a criterion validity test. A sample of
      the cohort workers (n=152) was observed at the workplace during four 30 min
      periods randomly distributed along the shift. At the end of the work shift, the
      questionnaire was filled in both by the worker and the observer. Agreements were
      tested between self-reports and observations, and between self-reports and
      observer opinion. Secondly, a comparison of exposure-effect relationships based
      on self-reports to those based on observations was carried out on the whole study
      cohort (n=716). Both sets of Relative Risks of being an incident case (LBP
      lasting at least 7 consecutive days in the follow-up year) were tested for
      heterogeneity. RESULTS: Self-reports agreement levels were better with observer
      opinion than with observational data and were higher for answers at a dichotomous
      level. Vehicle driving, manual handling without estimation of weight and
      frequencies, or trunk bending without rotation showed a fair to good agreement
      with the external criteria. Limits in the validation procedure did not allow
      validating the sitting and standing durations. As regards the health outcome
      comparison, questionnaire and observations led to homogeneous Relative Risks for
      the variables tested. CONCLUSIONS: Results show that self-reports provide a
      limited accuracy to assess actual frequencies and durations of work activities.
      Using a questionnaire, classifying the workers into exposure categories is rather
      relative, but questionnaire and observations seem similar in their relationships
      to outcome.

PMID- 16437222
TI  - Interaction between signalling pathways involved in skeletal muscle responses to
      endurance exercise.
AB  - The purpose of this review is to summarise the latest literature on the
      signalling pathways involved in transcriptional modulations of genes that encode
      contractile and metabolic proteins in response to endurance exercise. A special
      attention has been paid to the cooperation between signalling pathways and
      coordinated expression of protein families that establish myofibre phenotype.
      Calcium acts as a second messenger in skeletal muscle during exercise, conveying
      neuromuscular activity into changes in the transcription of specific genes. Three
      main calcium-triggered regulatory pathways acting through calcineurin, Ca(2+)
      calmodulin-dependent protein kinases (CaMK) and Ca(2+)-dependent protein kinase
      C, transduce alterations in cytosolic calcium concentration to target genes.
      Calcineurin signalling, the most important of these Ca(2+)-dependent pathways,
      stimulates the activation of many slow-fibre gene expression, including genes
      encoding proteins involved in contractile process, Ca(2+) uptake and energy
      metabolism. It involves the interaction between multiple transcription factors
      and the collaboration of other Ca(2+)-dependent CaMKs. Although members of
      mitogen-activated protein kinase (MAPK) pathways are activated during exercise,
      their integration into other signalling pathways remains largely unknown. The
      peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha
      (PGC-1alpha) constitutes a pivotal factor of the circuitry which coordinates
      mitochondrial biogenesis and which couples to the expression of contractile and
      metabolic genes with prolonged exercise.

PMID- 16437224
TI  - Supersaturation and renal precipitation: the key to stone formation?

PMID- 16437223
TI  - Regulation and modulation of electric waveforms in gymnotiform electric fish.
AB  - Weakly electric gymnotiform fish specialize in the regulation and modulation of
      the action potentials that make up their multi-purpose electric signals. To
      produce communication signals, gymnotiform fish modulate the waveforms of their
      electric organ discharges (EODs) over timescales spanning ten orders of magnitude
      within the animal's life cycle: developmental, reproductive, circadian, and
      behavioral. Rapid changes lasting milliseconds to seconds are the result of
      direct neural control of action potential firing in the electric organ.
      Intermediate-term changes taking minutes to hours result from the action of
      melanocortin peptides, the pituitary hormones that induce skin darkening and
      cortisol release in many vertebrates. Long-term changes in the EOD waveform
      taking days to weeks result from the action of sex steroids on the electrocytes
      in the electric organ as well as changes in the neural control structures in the
      brain. These long-term changes in the electric organ seem to be associated with
      changes in the expression of voltage-gated ion channels in two gene families.
      Electric organs express multiple voltage-gated sodium channel genes, at least one
      of which seems to be regulated by androgens. Electric organs also express
      multiple subunits of the shaker (Kv1) family of voltage-gated potassium channels.
      Expression of the Kv1 subtype has been found to vary with the duration of the
      waveform in the electric signal. Our increasing understanding of the mechanisms
      underlying precise control of electric communication signals may yield
      significant insights into the diversity of natural mechanisms available for
      modifying the performance of ion channels in excitable membranes. These
      mechanisms may lead to better understanding of normal function in a wide range of
      physiological systems and future application in treatment of disease states
      involving pathology of excitable membranes.

PMID- 16437225
TI  - Comments on "Health economic evaluation in lumbar spinal fusion. A systematic
      literature review anno 2005".

PMID- 16437226
TI  - [Quality of life and patient satisfaction after breast reconstruction].
AB  - BACKGROUND: Nowadays, the array of methods for reconstruction of the female
      breast following mastectomy is vast. In this study, we investigate and compare
      quality of life after breast reconstruction and satisfaction with the results of
      two commonly used techniques (autologous tissue vs. expander/implant). METHODS:
      Ninety-one consecutive patients who underwent breast reconstruction at a German
      clinic between 1996 and 2001 were included in the study. Patient satisfaction and
      quality of life were assessed retrospectively using self-evaluation
      questionnaires. RESULTS: Patients were generally more satisfied with the outcome
      of the operation when autologous tissue was used. This was significant in the
      following areas: breast size, form, definition of the lower breast fold, softness
      of the breast, and symmetry of the breasts. In both groups the quality of life
      following breast reconstruction at least 2 years after the operation was equal to
      that of healthy women of the same age group. CONCLUSION: Although patients were
      more satisfied with the results of autologous breast reconstruction, procedure
      choice did not affect quality of life.

PMID- 16437227
TI  - [Severing of the tibial nerve with stripping of the lesser saphenous vein--a rare
      complication of surgery for varicosity].
AB  - Neurological complications are rare with surgery for varicosities and usually
      involve the saphenous, peroneal, or sural nerve. When the saphenous vein is
      stripped in the popliteal region, there is danger of tibial nerve injury due to
      the topographic situation. We report a serious complication involving an
      iatrogenic extended lesion of the tibial nerve in the popliteal fossa that
      occurred in the course of a crossectomy and exeresis of the lesser saphenous
      vein. The complicated microsurgical reconstruction of this complex nerve injury
      is described, and the causes and errors leading to it are analyzed.

PMID- 16437228
TI  - [Transsexuals' life satisfaction after gender transformation operations].
AB  - BACKGROUND: More and more frequently, the registration of life satisfaction is
      being used to evaluate different medical treatments. So far, there have been only
      few such surveys on transsexuals (TS). Therefore, the aim of this study was to
      evaluate the general and the health-related life satisfaction of transsexuals
      after gender transformation operations. PATIENTS AND METHODS: Forty patients took
      part in this German cross-sectional study. The Questions on Life Satisfaction
      Module (FLZ) and free questions on different aspects of the new gender identity
      were used as measuring instruments. RESULTS: Of the TS studied, 85-95% were "very
      satisfied" or "satisfied" with the results of their gender transformation
      operation in respect to gender identity. The TS were significantly less satisfied
      (P>0.001) in overall "general life satisfaction" than the general population. In
      overall FLZ scores for "health-related life satisfaction", no differences were
      seen. CONCLUSION: These data indicate a discrepancy between subjective
      satisfaction with new gender identity and current life situation, and they
      identify problems with life satisfaction.

PMID- 16437229
TI  - [Isolated injury of the gallbladder. A rare cause of hemorrhagic shock after
      blunt abdominal trauma in a patient with liver cirrhosis].
AB  - Isolated injuries to the gallbladder are extremely rare in blunt abdominal
      trauma, with a reported incidence of less than 2%. We report a case with partial
      avulsion of the gallbladder and subsequent hemorrhagic shock in a patient with
      liver cirrhosis. Although the gallbladder injury was demonstrated on CT images
      (with contrast enhancement in the bed of the gallbladder), the correct diagnosis
      was not established preoperatively. Emergency laparotomy revealed partial
      avulsion of the gallbladder and the underlying condition of severe liver
      cirrhosis with ascites. We estimate that the gallbladder avulsion occurred due to
      compressional waves of the ascites (during blunt abdominal injury) which may have
      sheared off the gallbladder from the cirrhotic liver. The patient received
      cholecystectomy, which is recommended as standard in case of gallbladder injury.

PMID- 16437230
TI  - [Burned palm reconstruction. Current concepts regarding grafting techniques,
      sensibility and hand function].
AB  - BACKGROUND: The purpose of this study was to evaluate the results of conservative
      and operative treatment for burn injuries in the palmar region of the hand.
      METHODS AND CLINICAL MATERIAL: One hundred ten patients from the severe burn
      center in Ludwigshafen, Germany were evaluated a mean of 28 months
      postoperatively. Sixty-one had been treated with split-thickness skin grafts (43
      sheet and 18 mesh grafts). In addition to subjective evaluation (including pain
      assessment and aesthetic outcome rating by visual analog scale), objective
      outcome analysis included clinical tests, measurement of active range of motion
      and grip strength, and sensibility testing with the two-point discrimination and
      Semmes-Weinstein monofilament tests. RESULTS: Of the patients, 90% were satisfied
      with the results, showing excellent pain relief with an average score under 13 on
      the visual analog scale. Aesthetic outcome was rated good with sheet grafts; in
      appearance, mesh grafts tended to be rated average or insufficient. Functional
      outcome tests demonstrated a significant correlation between depth of injury and
      range of motion. Grip strength analysis revealed superior results with sheet
      grafts. Sensibility in the injured areas was lower than on the contralateral
      hands. The Semmes-Weinstein test average was 3.4 degrees at the burned area vs
      3.0 degrees in healthy hands, underscoring lower sensibility after burns.
      CONCLUSION: Surgical treatment of burned palms leads to good subjective and
      objective results, if specialized burn units are involved. Overall sheet
      transplantation seems to be the better choice for surgical reconstruction of the
      palmar burned hand.

PMID- 16437231
TI  - [Surgical treatment of groin soft tissue defects].
AB  - BACKGROUND: Treatment of groin defects remains challenging due to their location
      and origin. Such defects commonly result from resection of tumours but can also
      occur after surgical or medical therapy. MATERIAL AND METHODS: From 2003 to 2005,
      11 patients were treated with groin defects following radiation therapy and
      resection of lymph node metastasis, primary carcinoma, and sarcoma. Seven
      patients received wound closure with rectus femoris muscle flaps, and three had
      vertical rectus abdominis muscle flaps. One patient was amputated at the hip, and
      the defect was covered with dorsally pedicled muscle and skin flaps. RESULTS: All
      flaps healed primarily. There were no secondary infections or lymphorrhea.
      CONCLUSION: The flaps described here are well vascularised standard flaps which
      are easily harvested with no major donor site morbidity. They provide sufficient
      coverage for the groin, reduce long-term conservative treatment, hospitalisation,
      and problems such as scar contracture.

PMID- 16437232
TI  - [Establishing ophthalmology in the research framework programs of the European
      Union].
AB  - The framework programmes (FP) of the European Commission have substantially
      contributed to the funding of research within the European countries. The
      contribution of the funding provided by the EU relative to the funding available
      on the national level has steadily increased. European ophthalmology and vision
      research has benefited from this support provided by the EU. This review
      introduces the European funding policies and the European Research Area (ERA) and
      provides a list of all projects in ophthalmology and vision research that have
      been funded within FP1 to FP6. As an example for new instruments within FP6,
      Integrated Projects, the EVI-GENORET project is introduced. Finally an outlook
      for FP7 is provided.

PMID- 16437233
TI  - [Conventional perimetry. Part 3: Static perimetry: grid--strategy-
      visualisation].
AB  - Methods for visual field examination using static strategies began with manual
      static profile perimetry. The transition from a linear stimulus alignment along
      the profile section to a two-dimensional grid arrangement introduced the era of
      static grid perimetry. The use of computers makes it possible to automate and
      standardise this process, allowing the examiner to choose the visual field area,
      an adequate grid and the optimal strategy, while leaving the processing,
      visualisation and recording completely observer-independent. This contribution is
      based only on conventional static procedures for visual field examination (the
      use of white on white perimetry) as this technique is easily accessible,
      standardised and well established in everyday practice.

PMID- 16437235
TI  - Posttraumatic pseudolipoma: MRI appearances.

PMID- 16437236
TI  - [Shoulder pain and muscle weakness].

PMID- 16437237
TI  - [MRI of pulmonary perfusion].
AB  - Lung perfusion is a crucial prerequisite for effective gas exchange.
      Quantification of pulmonary perfusion is important for diagnostic considerations
      and treatment planning in various diseases of the lungs. Besides disorders of
      pulmonary vessels such as acute pulmonary embolism and pulmonary hypertension,
      these also include diseases of the respiratory tract and lung tissue as well as
      pulmonary tumors. This contribution presents the possibilities and technical
      requirements of MRI for diagnostic work-up of pulmonary perfusion.

PMID- 16437238
TI  - [Oxygen-enhanced MRI of the lung: optimized calculation of difference images].
AB  - BACKGROUND: In oxygen-enhanced lung MRI, difference maps of acquisitions during
      inhalation of room air and pure oxygen are calculated to assess lung function.
      The purpose of this study was to analyze how the calculation of these difference
      maps depends on the delayed signal change after switching the gas supply.
      METHODS: Ten healthy volunteers were examined with an ECG and respiratory
      triggered T1-weighting inversion recovery HASTE sequence with parallel imaging.
      Four blocks with 20 repetitions of up to 6 coronal slices were continuously
      acquired; in blocks 1 and 3 room air was supplied, in blocks 2 and 4 oxygen. Data
      were postprocessed, discarding between 0 and 19 repetitions after each change of
      gas supply before calculating the relative signal difference. RESULTS: The
      averaged relative signal difference increases from 9.4 to 17.4% when the number
      of discarded acquisitions increases; the ratio of signal difference and spatial
      standard deviation reaches a maximum at 5-8 discarded acquisitions. CONCLUSIONS:
      An optimized ratio of signal difference and statistical error is found if about 5
      8 of 20 respiratory-triggered repetitions are discarded after each change of gas
      supply for the calculation of difference maps.

PMID- 16437239
TI  - [MRI in mucoviscidosis (cystic fibrosis)].
AB  - Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs.
      Pulmonary manifestation is crucial for the prognosis and life expectancy of
      patients. Imaging modalities and lung function tests reflect the pulmonary status
      in these patients. The standard imaging modality for diagnosis and follow-up of
      pulmonary changes is chest x-ray. The gold standard for the detection of
      parenchymal lung changes remains high resolution computed tomography (HRCT), but
      this is not used routinely for CF-patients due to radiation exposure. Magnetic
      resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis
      lung disease, as shown in studies from the 1980s and early 1990 s. The continuing
      improvement of MRI techniques, however, has allowed for an adequate application
      of this non-radiation method in diagnosing the major pulmonary findings in CF, in
      addition to the assessment of lung function.

PMID- 16437240
TI  - Effects of parasitic helminths and ivermectin treatment on clinical parameters in
      the European wild boar (Sus scrofa).
AB  - Limited information exists on serum biochemistry and haematology of the European
      wild boar, and few correlations have been found between parasitic burden and
      clinical parameters in this species. Naturally infected wild boars were
      experimentally treated to study the effect of nematode parasites and ivermectin
      treatment on phytohaemagglutinin (PHA) skin reaction and haematological and serum
      biochemical parameters. White blood cells decreased in untreated wild boars,
      whereas triglyceride, lactate and creatinine concentrations increased in
      ivermectin-treated wild boars, and total protein and aspartate aminotransferase
      activity increased in both groups. Band neutrophils variation was positively
      correlated with the number of total adult parasites. Band neutrophils, creatinine
      and total protein variations were negatively correlated with both total egg
      counts and Metastrongylus eggs per gram variations. Alkaline phosphatase activity
      showed a negative correlation with Ascaris sp. eggs. The PHA skin reaction was
      positively correlated with the number of total adult parasites in untreated wild
      boars and with Metastrongylus sp. eggs of all wild boars at time 0. Two models
      including leukocytic and serum biochemical parameters were also highly correlated
      with the variation of Metastrongylus sp. eggs. Clinical parameters were thus in
      our study affected by helminth parasitism in the European wild boar, particularly
      those related to nutrients uptake, physical condition and immune response.
      Therefore, they could be useful in studies on subclinical effects of parasites,
      and parasitic burden must be considered when assessing the physical condition of
      European wild boars through haematological and serum biochemical parameters.

PMID- 16437241
TI  - The locus and modulation of the location negative priming effect.
AB  - Responding to the location of a target is slower when it appears at a recent
      distractor location [ignored-repetition (IR) trial] than when it arises at a new
      position [control (CO) trial], defining the location negative priming (NP)
      effect. On IR trials, both the distractor location and response are from the
      prior trial, and the locus question asks whether the delayed responding that
      arises is caused by the reused distractor position (i.e., a location locus) or
      the need to execute a distractor output (i.e., a response locus). A location NP
      procedure was used, incorporating a many:1 location-to-response mapping design,
      along with a response cue on some trials. A response locus for the location NP
      effect was indicated. Distractor-turned-target responses took longer to initiate
      than new outputs (many:1 paradigm), and valid response cues reduced distractor
      response interference and the location NP effect. Importantly, a possible S-R
      compatibility problem within the many:1 S-R paradigm was not supported.

PMID- 16437242
TI  - Asymmetric short-term adaptation of the vertical vestibulo-ocular reflex in
      humans.
AB  - Anatomical and electrophysiological studies have demonstrated up-down asymmetries
      in vertical ocular motor pathways. We investigated whether these asymmetries
      extend to the capacity for short-term adaptation of the vertical vestibulo-ocular
      reflex (VVOR) in humans. Specifically, we asked whether smooth pursuit signals
      are sufficient to asymmetrically adapt the VVOR. Healthy human subjects (N=8),
      positioned 90 degrees left-ear-down and fixating with their eyes upon a small
      laser dot (diameter: 0.1 degrees) projected on a sphere (distance: 1.4 m) were
      trained toward low VVOR gain for 30 min with symmetric and asymmetric visual VVOR
      cancellation paradigms, while being oscillated (0.2 Hz, +/-20 degrees) on a
      motorized turntable about the interaural earth-vertical axis. During asymmetric
      VVOR cancellation, the target was head-fixed in either the pitch-up or pitch-down
      half-cycles of oscillation (= trained direction) and space-fixed during the other
      half-cycles (= untrained direction). During symmetric VVOR cancellation, the
      target was head-fixed throughout the oscillations. Before and after adaptation,
      the pitch-up and pitch-down VOR gains were assessed during turntable oscillation
      in complete darkness. Before adaptation, average gains of pitch-up (0.75+/-0.15
      SD) and pitch-down (0.79+/-0.19 SD) VOR were not significantly different (paired
      t test: P>0.05). On an average, relative gain reductions induced by selective
      pitch-up (pitch-up VOR: 32%; pitch-down VOR: 21%) and pitch-down (pitch-up VOR:
      18%; pitch-down VOR: 30%) VOR cancellation were significantly (P<0.05) larger in
      the trained than in the untrained direction. Symmetric visual VVOR cancellation
      led to a significantly (P<0.01) larger relative gain reduction of the pitch-down
      (41%) than the pitch-up (33%) VOR. None of the paradigms led to significant
      changes of phase or offset. We conclude that, in human subjects, the smooth
      pursuit system is capable to asymmetrically decrease the gain of the VVOR equally
      well in both the upward and downward direction. The unexpected asymmetric
      decrease of the VVOR gain after symmetric visual cancellation may be related to
      the directional preferences of vertical gaze-velocity sensitive Purkinje cells in
      the flocculus for the downward direction.

PMID- 16437244
TI  - [Subtalar corrective arthrodesis in cases of post-traumatic arthrosis of the
      lower ankle joint].

PMID- 16437243
TI  - Low interleukin-10 production is associated with diabetes in HIV-infected
      patients undergoing antiviral therapy.
AB  - Reduced interleukin-10 (IL-10) production is associated with type 2 diabetes in
      elderly individuals. Antiviral therapy (ARV)-induced immune modulation results in
      diminished IL-10 production, and diabetes can be observed in ARV-treated human
      immunodeficiency virus (HIV)-infected individuals. We analyzed, in a cross
      sectional pilot study, HIV-antigen-stimulated IL-10 and tumor necrosis factor
      alpha (TNFalpha) production, and intracellular concentration (ICC), as well as B7
      H1 expression, a marker preferentially presented by IL-10-producing cells, in 20
      ARV-treated individuals in whom diabetes did (n=10; diabetes mellitus, DM) or did
      not (n=10; controls) develop. Pre-ARV glucose, cholesterol, and triglycerides
      levels, duration of HIV infection and of therapy, exposure to protease inhibitors
      (PI), HIV plasma viremia, CD4 counts, and nadir were similar in DM and control
      patients. Results showed that: (1) IL-10 production was lower; (2) IL-10 ICC was
      reduced; (3) B7-H1-expressing CD19(+) cells were diminished; and (4) TNFalpha
      production and ICC by CD4(+) T cells was augmented in DM patients. Development of
      diabetes in HIV infected, ARV-treated individuals could be a response to therapy.
      Similar to what is observed in elderly individuals, low IL-10 production is
      associated with diabetes in antiviral-treated HIV infection. Further studies will
      be necessary to clarify whether low IL-10 is a risk factor for, or a consequence
      of, diabetes.

PMID- 16437245
TI  - [The clinical use of the ISO-C(3D) imaging system in calcaneus fracture surgery].
AB  - We compared in a prospective study including 82 patients treated with ORIF of an
      intraarticular calcaneus fracture the quality of fluoroscopy, intraoperatively
      Iso-C(3D) and postoperative CT-scans. Therefore the posterior facet of the
      calcaneus (PFOC) was divided into three sectors. Joint steps and fracture gaps
      were detected by two independent investigators and statistically analysed.
      Another focus was to evaluate if the findings due to intraoperatively Iso-C(3D)
      assessment performed by the surgeon were correct and subsequently influenced the
      surgical procedure. There were no statistically differences between the Iso-C(3D)
      and CT findings concerning joint steps or fracture gaps in PFOC sectors I-III.
      With fluoroscopy an assessment of the PFOC sectors I and II was not possible. In
      six cases (7.3%), intraoperative reduction was redone after performing an Iso
      C(3D) scan. In ten cases, 12 malpositioned screws were replaced (12.2%/14.6%).
      These results suggest that intraoperative 3D Iso-C(3D) imaging provides a high
      diagnostic reliability. By careful assessment of the images the surgeons receive
      information which could lead to a change of the operative strategy.

PMID- 16437246
TI  - [Management of postoperative objectified intravesical position of the TVT tape-
      two case reports].
AB  - Recurrent urinary tract infections and symptoms of a hyperactive bladder in women
      having undergone a TVT (tension-free vaginal tape) procedure may be due to
      intravesical position of the tape. Urogenital ultrasound can provide early
      preliminary diagnostic evidence, which can then be confirmed by subsequent
      urethrocystoscopy. Minimally invasive revision can be achieved by transurethral
      resection of the intravesical TVT portions. Tape portions near the wall can be
      removed after stretching of the tape with grasping forceps inserted through a
      suprapubically placed trocar. This simple procedure can spare the patient a more
      extensive repeat operation for removal of the intravesical TVT that may even
      require a combined abdominovaginal approach.

PMID- 16437247
TI  - [Single-use intermittent catheterisation].
AB  - In patients with bladder dysfunctions, intermittent catheterisation is a bladder
      evacuation technique with a low complication rate. Therefore, it is regarded as
      the method of choice in the treatment of chronic residual urine, mostly due to a
      hypo- or acontractile detrusor. Regarding the incidence of urinary tract
      infections and urethral strictures, aseptic catheterisation seems to be superior
      to the clean technique. There are, however, no independent, prospective,
      controlled, randomised, double-blinded studies comparing the different catheter
      types. Thus, the question of which catheter is the ideal one cannot be answered
      yet. Predominantly in patients who have to perform intermittent catheterisation
      for good, the prevention of long-term complications, especially of the upper
      urinary tract, is of the utmost importance. In the long run, using an inadequate
      technique and catheters not optimally designed will clearly lead to a higher
      complication rate. Despite the lower prices of certain catheters, treatment of
      these complications will lead to higher instead of lower costs. The data
      available today clearly demonstrate that aseptic intermittent catheterisation is
      the technique of choice today. Important details of this treatment modality,
      however, have to be elucidated by prospective studies in the future.

PMID- 16437248
TI  - [Intravesical therapy for overactive bladder].
AB  - INTRODUCTION: Despite recent advances in the field of anticholinergic drugs, lack
      of efficiency and side effects are still the main reasons for discontinuation of
      treatment. The introduction of botulinum A toxin was a milestone in the treatment
      of detrusor overactivity. The treatment, however, is invasive, the duration of
      the treatment effects is limited, and long-term results are not yet available.
      The following addresses therapeutic alternatives to local treatment of overactive
      bladder. MATERIALS AND METHODS: A total of 52 patients received intravesical
      oxybutynin. In 16 patients, capsaicin was instilled in the bladder and 28
      patients were treated with EMDA. RESULTS: Intravesical oxybutynin was successful
      in 86%; the success rate of capsaicin instillation was 47%. EMDA was successful
      in 78%. Two transient ischemic attacks following EMDA were observed as
      significant side effects. CONCLUSION: Besides botulinum A toxin, several
      effective treatment options are available for patients with detrusor overactivity
      refractory to oral anticholinergic treatment. Therefore, in each individual
      patient, possible risks and complications of the different treatment options
      should be considered thoroughly to find the optimal method in each case.

PMID- 16437249
TI  - [Neurourology. Current developments and therapeutic strategies].
AB  - There is no part of urology that has made so much progress in the last 25 years
      as neurourology. Seminal developments have been made in the selective
      effectiveness of drugs influencing neurogenic bladder dysfunction but having
      limited side effects. Additional advances are also likely to be made in the
      methods of functional electrostimulation and tissue engineering. Neurourology is
      predominantly influenced by our dynamic-functional understanding and the
      functionally oriented planning and implementation of treatment. The initial
      treatment options in many areas of neurourology are conservative, but, when
      possible, not irreversible. If these are ineffective or lead to late
      complications (e.g. by congenital paraplegia), there are a series of organ
      sparing or organ manipulating operations which can restore organ function. These
      make it possible to save kidney function from continuing damage, and, in many
      cases, to restore continence. The permanent indwelling catheter should remain
      excluded from the treatment of neurogenic bladder dysfunction. With adequate
      treatment, patients with neurogenic bladder dysfunction can be protected from
      severe complications and reintegrated into their normal social environment. After
      the acute phase of rehabilitation, urology is the most commonly required
      specialist area for paraplegic patients. In the past, urological problems have
      contributed most to the short lifespan of patients with an accident related
      spinal cord injury. Using modern neurourological treatment strategies, not only
      is lifespan increased but the quality of life of the patient is permanently
      improved.

PMID- 16437250
TI  - Biocompatibility testing of novel multifunctional polymeric biomaterials for
      tissue engineering applications in head and neck surgery: an overview.
AB  - Biomaterial research and tissue engineering are rapidly growing scientific fields
      that need an interdisciplinary approach where clinicians should be included from
      the onset. Biocompatibility testing in vitro and in vivo comprise the agarose
      overlay test, the MTT test, direct cell seeding tests and the chorioallantoic
      membrane test for angiogenic effects, among others. Molecular biology techniques
      such as real-time polymerase chain reaction and microarray technology facilitate
      the investigation of tissue integration into biomaterials on a cellular and
      molecular level. The physicochemical characterization of biomaterials is
      conducted using such methods as X-ray photoelectron spectroscopy (XPS) and
      scanning electron microscopy (SEM). Excellent biocompatibility and
      biofunctionality were demonstrated for a series of recently developed
      multifunctional biodegradable, polymeric biomaterials both in vitro and in vivo.
      Novel, multifunctional polymeric biomaterials offer a highly specific adjustment
      to the physiological, anatomical and surgical requirements and can thereby
      facilitate new therapeutic options in head and neck surgery.

PMID- 16437251
TI  - Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT
      11)-induced delayed diarrhea.
AB  - PURPOSE: An antitumor camptothecin derivative CPT-11 has proven a broad spectrum
      of solid tumor malignancy, but its severe diarrhea has often limited its more
      widespread use. We have demonstrated from a rat model that intestinal beta
      glucuronidase may play a key role in the development of CPT-11-induced delayed
      diarrhea by the deconjugation of the luminal SN-38 glucuronide, and the
      elimination of the intestinal microflora by antibiotics or dosing of TJ-14, a
      Kampo medicine that contains beta-glucuronidase inhibitor baicalin, exerted a
      protective effect. In the present study, we assessed the efficacy of several
      potential treatments in our rat model to clarify which is the most promising
      treatment for CPT-11-induced delayed diarrhea. METHODS AND RESULTS: Oral dosing
      (twice daily from days -1 to 4) of streptomycin 20 mg/kg and penicillin 10 mg/kg
      (Str/Pen), neomycin 20 mg/kg and bacitracin 10 mg/kg (Neo/Bac), both of which
      inhibited almost completely the fecal beta-glucuronidase activity, or TJ-14 1,000
      mg/kg improved the decrease in body weight and the delayed diarrhea symptoms
      induced by CPT-11 (60 mg/kg i.v. from days 1 to 4) to a similar extent. The
      efficacy was less but significant in activated charcoal (1,000 mg/kg p.o. twice
      daily from days -1 to 4). In a separate experiment using rats bearing breast
      cancer (Walker 256-TC), TJ-14, Neo/Bac, and charcoal at the same dose regimen
      improved CPT-11-induced intestinal toxicity without reducing CPT-11's antitumor
      activity. In contrast, oral dosing (twice a day) of cyclosporin A (50 mg/kg), a P
      glycoprotein and cMOAT/MRP2 inhibitor or valproic acid (200 mg/kg), a UDP
      glucuronosyltranferase inhibitor, exacerbated the intestinal toxicity without
      modifying CPT-11's antitumor activity. CONCLUSIONS: The result clearly
      demonstrated the ability of Neo/Bac, Str/Pen, and TJ-14, less but significant
      ability of activated charcoal, to ameliorate CPT-11-induced delayed-onset
      diarrhea, suggesting the treatments decreasing the exposure of the intestines to
      the luminal SN-38 are valuable for improvement of CPT-11-induced intestinal
      toxicity. In contrast, the treatments affecting the biliary excretion of CPT-11
      and its metabolites might have undesirable results.

PMID- 16437252
TI  - Cloning, characterisation, and heterologous expression of the Candida utilis
      malic enzyme gene.
AB  - The Candida utilis malic enzyme gene, CME1, was isolated from a cDNA library and
      characterised on a molecular and biochemical level. Sequence analysis revealed an
      open reading frame of 1,926 bp, encoding a 641 amino acid polypeptide with a
      predicted molecular weight of approximately 70.2 kDa. The inferred amino acid
      sequence suggested a cytosolic localisation for the malic enzyme, as well as 37
      and 68% homologies with the malic enzymes of Schizosaccharomyces pombe and
      Saccharomyces cerevisiae, respectively. Expression of the CME1 gene was subject
      to carbon catabolite repression and substrate induction, similar to the
      regulatory mechanisms observed for the C. utilis dicarboxylic acid permease. The
      CME1 gene was successfully expressed in S. cerevisiae under control of the S.
      cerevisiae PGK1 promoter and terminator. When coexpressed with the S. pombe
      malate permease gene (mae1), it resulted in a recombinant S. cerevisiae strain
      able to completely degrade 90% of the extracellular L-malate within 24 h.

PMID- 16437253
TI  - [Do relatives of patients with different mental disorders also differ in their
      attitudes towards these disorders?].
AB  - BACKGROUND: Studies on the attitudes of relatives of psychiatric patients have
      usually focused on views of causes and treatment options for schizophrenic
      disorders. Comparative surveys, especially those dealing with attitudes on social
      distance and restrictions, have to date been rather an exception. METHODS: In the
      present study, 161 relatives and other close reference persons of patients with
      schizophrenic, recurrent depressive, or bipolar affective disorder were
      interviewed with the German version of the Questionnaire on the Opinions of the
      Family between February and July 2003. RESULTS: Relatives of patients with
      schizophrenic disorder differ from the other two groups especially in attitudes
      displaying greater social distance toward mental disorders and less hope for
      social reintegration of these patients. Independently of the form of disorder,
      natural relatives exhibit the greatest social distance toward mental disorders.
      Differences in attitudes on the basis of patients' and relatives' socio
      demographic and clinical characteristics are rather scarce. CONCLUSIONS: Attitude
      toward mental disorders is an important trait of relatives supporting mentally
      ill persons. Differences in the effects of disorder-specific attitudes on
      relatives' well-being and their perception of burden have to be investigated
      further to enable the development of supportive strategies suited to the various
      groups of psychiatric patient relatives.

PMID- 16437255
TI  - [Fritz Flugel (1897-1973). Early research on neuroleptics].
AB  - In the early 1950s, Fritz Flugel and his colleagues at the Neurology Clinic of
      the University of Erlangen in Germany contributed greatly to the clinical
      introduction of chlorpromazine in German psychiatry. Flugel's clinical work made
      possible in exemplary fashion the first German psychiatric research on
      neuroleptics. Between 1953 and 1963, scientists were trying to find a theoretical
      explanation for the positive psychic effect which had become evident during
      empirical tests with the new substance. Within a few years, the new drug had its
      breakthrough, which simply was based on worldwide therapeutical success and good
      empirical results. That already had happened about 10 years before Carlsson came
      up with the first plausible theory of neuroleptic function by formulating the
      dopamine hypothesis in 1963. This brought new energy and developments in
      psychiatric research in general. Newly developed theses have thoroughly changed
      the therapeutic approach in psychiatry and the way in which pathophysiological
      contexts of the brain are understood.

PMID- 16437254
TI  - [Monoaminergic function in major depression. A possibly helpful tool for choosing
      treatment strategy].
AB  - Little is known about the variables that might predict outcome in major
      depression. Most studies do not imply any clinical consequences for treatment
      because their predictors were nonspecific and results did not differ between the
      different treatment options. Finding a variable that can predict the
      antidepressive treatment option best suited to an individual might help in
      reducing the considerable number of nonresponders in the treatment of depression.
      As most antidepressants influence the serotonergic or noradrenergic system,
      monoaminergic function at the start of therapy might be a possible specific
      response predictor. In this review, measures that can determine monoaminergic
      function are presented along with their relationship to treatment response, e.g.,
      monoaminergic metabolites, neuroendocrine challenge tests, evoked event-related
      potentials, genetics, and neuroimaging. In conclusion, the results of
      serotonergic functions are still heterogeneous, but the relationship between
      noradrenergic function and treatment response has not been investigated in any
      detail yet.

PMID- 16437257
TI  - Anatomically corrected malposition of the great arteries in the setting of
      aortopulmonary window associated with holoprosencephaly.

PMID- 16437259
TI  - Technique and follow-up of minimally invasive Heller myotomy for achalasia.
AB  - BACKGROUND: Laparoscopic Heller myotomy has been proven effective. Reliable
      predictive factors for outcome and the true benefit of the da Vinci robotic
      system, however, remain unknown. METHODS: Seventy patients underwent laparoscopic
      Heller myotomy. The number of intraoperative perforations and the symptom
      predictive value of postoperative esophagogram width measurement at the
      gastroesophageal junction were analyzed. RESULTS: The overall complication rate
      was 11%. Four patients experienced intraoperative perforation during the
      laparoscopic technique. No perforations were experienced with the da Vinci
      robotic system (n = 19). Of the total, 82% of patients had resolution of
      dysphagia, 91% of regurgitation, 91% of heartburn and 82% of chest pain.
      Immediate postoperative esophagogram gastroesophageal junction width demonstrated
      a positive predictive trend from 0 to 10 mm for dysphagia. CONCLUSION:
      Laparoscopic Heller myotomy is an effective treatment for achalasia. Immediate
      postoperative esophagogram gastroesophageal junction width measurement as a
      predictor for symptom resolution requires further study.

PMID- 16437260
TI  - A novel technique for fascial fixation of laparoscopic adjustable gastric band
      ports.
AB  - Access port dislodgement after laparoscopic adjustable gastric banding is a
      recurring problem that often requires operative revision. Securing the port to
      the abdominal wall fascia in the traditional way with standard instruments is
      challenging in obese patients due to a thick abdominal wall. Therefore, we have
      devised a novel and simple technique for access port fixation using the
      EndoStitch device.

PMID- 16437261
TI  - A groundbreaking new suturing device: the Excalibur.
AB  - BACKGROUND: Laparoscopic knot tying can be stressful. We reported two simple
      techniques, known as the Thumbs up! knot and the Tornado knot. We have further
      refined these procedures with the development of a new needle holder, called the
      Excalibur suturing needle holder. MATERIALS: This forceps differ from most
      conventional forceps in that the hinge is designed to stick out. The large hinge
      is stored out of the way when the forceps are closed, to prevent the thread
      accidentally catching. RESULTS: The thread is hooked on the projected hinge,
      which resembles the heel of a high-heel shoe. By using this forceps, the
      laparoscopic knot tying becomes easier for not only well experienced but also
      less experienced surgeons. CONCLUSIONS: The Excalibur, with its high heel, can
      complete knots with simple straight-line motion, making knot tying easier. This
      forceps will help reduce the stresses associated with intra-corporeal knot tying.

PMID- 16437262
TI  - Laparoscopic radiofrequency for hepatocellular carcinoma.

PMID- 16437264
TI  - Ultrasound-guided mechanical intraductal stone fragmentation and removal for
      sialolithiasis: a new technique.
AB  - BACKGROUND: Not all patients with sialolithiasis can be treated successfully by
      established minimally invasive techniques. METHODS: A forceps was used under
      sonographic control to fragment and retrieve salivary calculi in five cases
      refractory to established minimal invasive approaches. RESULTS: One patient with
      a sialolithiasis of the Stenon duct, two patients with a stone in the hilum
      region of the submandibular gland, and one patient with a sialolith in the
      sublingual gland were cured by this technique. For another patient, only a part
      of the stone in the hilum region of the submandibular gland could be removed. No
      relevant side effects occurred. CONCLUSIONS: To the authors' knowledge, this is
      the first report of a new, simple, and inexpensive minimally invasive technique
      that proved to be at least partially successful in the treatment of
      sialolithiasis in cases refractory to other therapies. The technique also seems
      to be suitable as a primary treatment approach.

PMID- 16437263
TI  - Thoracic sympathicolysis for primary hyperhidrosis: a review of 918 procedures.
AB  - BACKGROUND: Bilateral upper thoracic sympathectomy or sympathicolysis, currently
      the standard treatment for palmar or axillary hyperhidrosis, is regarded as a
      safe procedure. This study evaluates the quantitative and qualitative incidence
      of intraoperative and postoperative complications resulting from bilateral
      thoracic sympathicolysis. METHODS: From 1996 to 2004, 458 consecutive patients
      with primary hyperhidrosis underwent surgery. These patients comprised 143 men
      (31.2%) and 315 women (68.7%) with a mean age of 26 years (range, 14-52 years).
      In all but seven cases, the procedure was bilaterally synchronous. RESULTS: No
      mortality was recorded. The anhydrosis rate was 97.4%, with a hypohidrosis rate
      of 2.4% and a failure rate of 0.2%. The latter was resolved with reintervention.
      The mean hospital stay was 17 h. The rate of major perioperative complications
      with conversion to thoracotomy was 0.4%. The overall rate of postoperative
      complications was 3.6%. The complications and rates observed were as follows:
      pneumothorax (2.06%), subcutaneous emphysema (1.08%), pleural bleeding (0.2%),
      hemothorax (0.1%), and atelectasis (0.1%). Compensatory hyperhidrosis was
      observed in 48.4% of the patients, but the sensation of compensatory
      hyperhidrosis was reported in 85.6% of the cases. Excessive dryness of the hands
      was reported in 0.38%, Horner's syndrome in 0.32%, and gustatory hyperhidrosis in
      1.1% of the cases. The overall satisfaction rate was 88.5%. CONCLUSIONS: The
      results suggest that endoscopic bilateral thoracic sympathicolysis is an
      effective method for managing primary hyperhidrosis, especially severe palmar
      hyperhidrosis, but it is necessary to inform patients fully concerning the
      undesirable effects.

PMID- 16437265
TI  - Laparoscopic cholecystectomy under spinal anesthesia: a pilot study.
AB  - BACKGROUND: Regional anesthesia has not been used as the sole anesthetic
      procedure other than in the scenario of a patient at high risk to undergo
      laparoscopic cholecystectomy with CO2 pneumoperitoneum under general anesthesia.
      METHODS: Fifteen ASA grade I or II patients underwent laparoscopic
      cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia.
      Intraoperative parameters, postoperative pain and recovery in general, as well as
      patient satisfaction at follow-up were prospectively recorded in a pilot study to
      assess the feasibility and safety of the procedure. RESULTS: All operations were
      completed laparoscopically and conversion from spinal to general anesthesia was
      not required in any of the cases. Median pain score 4 h postoperatively was 1.5
      (range, 0-5), at 8 h it was 1 (range, 0-6), and at 24 h it was 1 (range, 0-4).
      All patients were discharged after 24 h. Follow-up 2 weeks postoperatively showed
      all but one patient to be satisfied and strongly recommending the anesthetic
      procedure. CONCLUSION: Laparoscopic cholecystectomy with low-pressure CO2
      pneumoperitoneum can be successfully and safely performed under spinal
      anesthesia. Furthermore, it seems that spinal anesthesia is associated with
      minimal postoperative pain and at least an equally good recovery as with general
      anesthesia.

PMID- 16437266
TI  - The role of mental rotation and memory scanning on the performance of
      laparoscopic skills: a study on the effect of camera rotational angle.
AB  - OBJECTIVE: The rotational angle of the laparoscopic image relative to the true
      horizon has an unknown influence on performance in laparoscopic procedures. This
      study evaluates the effect of increasing rotational angle on surgical
      performance. METHODS: Surgical residents (group 1) (n = 6) and attending surgeons
      (group 2) (n = 4) were tested on two laparoscopic skills. The tasks consisted of
      passing a suture through an aperture, and laparoscopic knot tying. These tasks
      were assessed at 15 degrees intervals between 0 degrees and 90 degrees , on three
      consecutive repetitions. The participant's performance was evaluated based on the
      time required to complete the tasks and number of errors incurred. RESULTS: There
      was an increasing deterioration in suturing performance as the degree of image
      rotation was increased. Participants showed a statistically significant 20-120%
      progressive increase in time to completion of the tasks (p = 0.004), with error
      rates increasing from 10% to 30% (p = 0.04) as the angle increased from 0 degrees
      to 90 degrees. Knot-tying performance similarly showed a decrease in performance
      that was evident in the less experienced surgeons (p = 0.02) but with no obvious
      effect on the advanced laparoscopic surgeons. CONCLUSIONS: When evaluated
      independently and as a group, both novice and experienced laparoscopic surgeons
      showed significant prolongation to completion of suturing tasks with increased
      errors as the rotational angle increased. The knot-tying task shows that
      experienced surgeons may be able to overcome rotational effects to some extent.
      This is consistent with results from cognitive neuroscience research evaluating
      the processing of directional information in spatial motor tasks. It appears that
      these tasks utilize the time-consuming processes of mental rotation and memory
      scanning. Optimal performance during laparoscopic procedures requires that the
      rotation of the camera, and thus the image, be kept to a minimum to maintain a
      stable horizon. New technology that corrects the rotational angle may benefit the
      surgeon, decrease operating time, and help to prevent adverse outcomes.

PMID- 16437267
TI  - Laparoscopic mesh hiatoplasty for paraesophageal hernias and fundoplications: a
      critical analysis of the available literature.
AB  - BACKGROUND: Little grade A medical evidence exists to support the use of
      prosthetic material for hiatal closure. Therefore, the authors compiled and
      analyzed all the available literature to determine whether the use of prosthetic
      mesh in hiatoplasty for routine laparoscopic fundoplications (LF) or for the
      repair of large (>5 cm) paraesophageal hernias (PEH) would decrease recurrence.
      METHODS: A literature search was performed using an inclusive list of relevant
      search terms via Medline/PubMed to identify papers (n = 19) describing the use of
      prosthetic material to repair the crura of patients undergoing laparoscopic PEH
      reduction, LF, or both. RESULTS: Case series (n = 5), retrospective reviews (n =
      6), and prospective randomized (n = 4) and nonrandomized (n = 4) trials were
      identified. Laparoscopic procedures (n = 1,368) were performed for PEH,
      gastroesophageal reflux disease (GERD), hiatal hernia, or a combination of the
      three. Group A (n = 729) had primary suture repair of the crura, and group B (n =
      639) had repair with either interposition of mesh to close the hiatus or onlay of
      prosthetic material after hiatal or crural closure. The use of mesh was
      associated with fewer recurrences than primary suture repair in both the LF and
      PEH groups. The mean follow-up period did not differ between the groups (20.7
      months for group A vs. 19.2 months for group B). None of the papers cited any
      instance of prosthetic erosion into the gastrointestinal tract. CONCLUSIONS: The
      current data tend to support the use of prosthetic materials for hiatal repair in
      both routine LF and the repair of large PEHs. Longer and more stringent follow-up
      evaluation is necessary to delineate better the safety profile of mesh
      hiatoplasty. Future randomized trials are needed to confirm that mesh repair is
      superior to simple crural closure.

PMID- 16437268
TI  - Management of common bile duct stones in a rural area of the United States:
      results of a survey.
AB  - BACKGROUND: Laparoscopic common bile duct exploration has been reported to be
      highly successful and cost-effective. It remains unknown to what extent the
      procedure is used in routine surgical practice. METHODS: We conducted a survey of
      general surgeons practicing in a rural area of the United States. The type of
      practice, laparoscopic training, performance of cholangiography, and preferred
      approach to choledocholithiasis were elicited. RESULTS: Sixty-eight of 207
      surveys (33%) were returned. Thirty respondents (45%) indicated that they perform
      laparoscopic common bile duct explorations. The likelihood of laparoscopic common
      bile duct exploration increased with a higher number of cholecystectomies per
      year (p < 0.05, chi-square) but was independent of training or routine
      cholangiography. The preferred approach to a patient with choledocholithiasis was
      endoscopic retrograde cholangiopancreatography (75%), followed by laparoscopic
      (21%) and open exploration (4%). Reasons for not performing laparoscopic
      exploration were time (58%), equipment (24%), good gastrointestinal backup (6%),
      reimbursement (3%), increased morbidity (1.5%), lack of skill (1.5%), and
      other/no reason (18%). CONCLUSION: Although 45% of practicing surgeons indicated
      that they perform laparoscopic common bile duct explorations, only 21% practiced
      it as their preferred approach. Time constraints and lack of equipment are the
      main factors preventing the application of the laparoscopic technique toward
      choledocholithiasis.

PMID- 16437269
TI  - Coagulation, inflammatory, and stress responses in a randomized comparison of
      open and laparoscopic repair of recurrent inguinal hernia.
AB  - BACKGROUND: In previous comparisons of inflammatory and stress responses to open
      (OR) and laparoscopic (LR) hernia repair, all operations were performed under
      general anesthesia. Since local anesthesia is widely used for OR, a comparison of
      this approach with LR seemed relevant. METHODS: Patients with recurrent inguinal
      hernia were randomized to OR under local anesthesia (n = 30) or LR under general
      anesthesia (n = 31). The magnitude of the surgical trauma was assessed by
      measuring markers of coagulation (prothrombin fragment 1 + 2), endothelial
      activation (von Willebrand factor), inflammation [leukocytes, interleukin-6, -8
      and -10, granulocyte macrophage colony-stimulating factor, and C-reactive protein
      (CRP)], and endocrine stress (cortisol) in blood collected before operation, 4 h
      postincision, and on postoperative day 2. RESULTS: Leukocyte counts and
      interleukin-6 and CRP levels increased in both groups, with the CRP increase
      being significantly greater in the OR group. The other markers did not increase
      significantly. CONCLUSION: The acute phase response was more pronounced after OR,
      even when this was done under local anesthesia. Both techniques seemed rather
      atraumatic.

PMID- 16437270
TI  - Laparoscopic resection of gastrointestinal stromal tumors: not all tumors are
      created equal.
AB  - BACKGROUND: Laparoscopic resection has become an accepted approach to
      gastrointestinal stromal tumors (GISTs), with acceptable early results published
      in the literature. Long-term recurrence rates, however, are still unclear, and
      the management of tumors in challenging locations requires exploration. METHODS:
      A retrospective analysis of all patients undergoing a laparoscopic resection of
      gastric GIST in our institution between November 1997 and July 2004 was
      performed. RESULTS: A total of 14 patients with 15 tumors were evaluated, 5 of
      which were located high on the lesser curve. All the patients had an attempted
      laparoscopic approach, with the following procedures performed: stapled wedge
      excision (n = 8), excision and manual sewing technique (n = 4), and distal
      gastrectomy (n = 1). Overall, there was a 15% (n = 2) conversion rate. Lesions
      found in the fundus and greater curvature areas were easily resected via simple
      stapled wedge excision. High lesser curve tumors were more difficult to manage
      and required a combination of methods for complete excision and preservation of
      the gastrointestinal junction including intraoperative gastroscopy, excision and
      manual sewing technique, and reconstruction over an esophageal bougie. There were
      no postoperative complications, and the length of hospital stay was 4.6 +/- 1.9
      days. At a median follow-up period of 46.5 months (mean, 37.4 +/- 26 months), one
      patient experienced a recurrence (18 months postoperatively), with eventual
      disease-related death. CONCLUSION: The laparoscopic approach to gastric GIST
      tumors is safe and associated with acceptable short- and intermediate-term
      results. High lesser curve GISTs can be safely approached laparoscopically using
      various techniques to ensure an adequate resection margin without compromise of
      the GE junction.

PMID- 16437271
TI  - Modified needlescopic video-assisted thoracic surgery for primary spontaneous
      pneumothorax : the long-term effects of apical pleurectomy versus pleural
      abrasion.
AB  - BACKGROUND: The objective of this study was to evaluate the feasibility and
      safety of modified needlescopic video-assisted thoracic surgery (VATS) for
      treating primary spontaneous pneumothorax. The efficacy between apical
      pleurectomy and pleural abrasion through this technique was also compared.
      METHODS: Between 2001 and 2003, 65 patients with primary spontaneous pneumothorax
      underwent modified needlescopic VATS procedures. The blebs were resected with
      endoscopic linear staplers. Pleurodesis was achieved by apical pleurectomy before
      September 2002 (n = 30) and by pleural abrasion for the remainder of the study
      period (n = 35). RESULTS: Mean operation time was 103 min in the pleurectomy
      group and 78 min in the abrasion group (p = 0.001). Complications developed in
      four patients (6.2%): prolonged air leaks in three patients and wound infection
      in one patient. The mean postoperative hospital stay was 3.8 +/- 1.8 days. The
      two groups had comparable doses of requested analgesics, complication rates,
      postoperative chest tube and hospital stays, and postoperative pulmonary function
      test. Ipsilateral recurrence did not occur in any of the pleurectomy group
      patients after a mean follow-up of 31 months, but it occurred in three patients
      (8.6%) in the abrasion group after a mean follow-up of 19 months. CONCLUSIONS:
      Modified needlescopic VATS provides a feasible and safe procedure for treating
      primary spontaneous pneumothorax. In terms of efficacy, apical pleurectomy is
      more effective in preventing ipsilateral recurrence than pleural abrasion.

PMID- 16437272
TI  - Predictive factors of coexisting cancer in Barrett's high-grade dysplasia.
AB  - BACKGROUND: Identification of high-grade dysplasia (HGD) in Barrett's esophagus
      has been considered an indication for esophagectomy because of the high risk for
      coexisting cancer. However, rigorous endoscopic surveillance programs recently
      have been recommended, reserving esophagectomy for patients whose cancer is
      identified on biopsy. This approach risks continued surveillance for patients who
      already have cancer unless reliable markers for the presence of occult cancer are
      identified. This study aimed to determine the endoscopic, histologic, and
      demographic features associated with the presence of occult cancer in patients
      with HGD. METHODS: Endoscopic, histologic, and demographic findings for 31
      patients who underwent esophagectomy for HGD were reviewed. The presence of an
      ulcer, nodule, stricture, or raised area on preoperative endoscopy was noted. The
      results of endoscopic biopsies taken before resection every 1 to 2 cm along the
      Barrett's segment were reviewed. The HGD was categorized as unilevel if the
      dysplasia was limited to one level of biopsy and as multilevel if more than one
      level was involved. Patients were divided into two groups according to the
      presence or absence of cancer in the resected specimens, and these variables were
      compared. RESULTS: The prevalence of coexisting cancer in patients with HGD was
      45% (14/31). Of the 31 patients in this study, 9 had a visible lesion. Cancer was
      found in the resected specimens from 7 (78%) of 9 patients with a visible lesion
      and 7 (32%) of 22 patients without a visible lesion (p = 0.019). Of 22 patients
      without a visible lesion, 10 had multilevel and 12 had unilevel HGD. The findings
      showed that 6 (60%) of 10 patients with multilevel HGD and 1 (8.3%) of 12
      patients with unilevel HGD had cancer in the resected esophagus (p = 0.009).
      CONCLUSION: For patients with HGD, a lesion visible on endoscopy and/or HGD at
      multiple biopsy levels is associated with an increased risk for coexisting
      cancer. These patients should be considered for early esophagectomy.

PMID- 16437273
TI  - Carbon dioxide insufflation attenuates parietal blood flow obstruction in
      distended colon: potential advantages of carbon dioxide insufflated colonoscopy.
AB  - BACKGROUND: Bowel distention after colonoscopy has been considered as a cause of
      blood flow disturbance. Carbon dioxide (CO2), with its higher absorbability and
      vasodilating effect, may reduce parietal blood flow disturbance of distended
      colon when used for intraluminal insufflation instead of air. The purpose of this
      study was to assess parietal blood flow of the colon distended with intraluminal
      air/CO2 insufflation. METHODS: A 5-cm segment of rat colon was insufflated with
      either air (air group) or CO2 (CO2 group). Two insufflation methods were
      employed: temporary insufflation up to an intraluminal pressure of 60 mmHg and
      continuous insufflation at a pressure of 5, 15, and 30 mmHg. Bowel distention and
      parietal blood flow measured by laser Doppler imaging were evaluated. RESULTS:
      For temporary insufflation, bowel distention was prolonged in the air group,
      whereas it rapidly resolved in the CO2 group. Parietal blood flow decreased in
      both groups; however, it recovered within 5 min in the CO2 group. For continuous
      insufflation, under 5 mmHg insufflation, blood flow decreased in the air group,
      whereas it increased in the CO2 group. Blood flow decreased in both groups under
      15 mmHg insufflation; however, it decreased less in the CO2 group. There was a
      reverse relationship between insufflation pressure and blood flow difference.
      Inhibition of nitric oxide synthase, ATP-sensitive K+ channel, or heme oxygenase
      was ineffective against a CO2-induced increase in blood flow. CONCLUSION: CO2
      insufflation preserved parietal blood flow not only by rapid resolution of bowel
      distention but also by its potential vasodilative effect.

PMID- 16437274
TI  - Laparoscopic appendectomy significantly reduces length of stay for perforated
      appendicitis.
AB  - INTRODUCTION: Though ruptured appendicitis is not a contraindication to
      laparoscopic appendectomy (LA), most surgeons have not embraced LA as the first
      line approach to ruptured appendicitis. In fact, in 2002, the Cochrane Database
      Review concluded: 1) the clinical effects of LA are "small and of limited
      clinical relevance," and 2) the effects of LA in perforated appendicitis require
      further study. OBJECTIVE: To study the effects of LA vs open appendectomy (OA)
      among adults with appendicitis. METHODS: In 2003, 272 adults underwent
      appendectomy at a large County hospital, and were enrolled in a prospective
      clinical pathway that detailed their hospital course from time of diagnosis to
      discharge. Data included patient demographics, time elapse from diagnosis to
      surgery, surgical technique (LA vs. OA), operative diagnosis (acute vs perforated
      appendicitis) and post-operative length of stay (LOS). RESULTS: Complete data was
      obtained for 264 (97%) patients. Patient demographics were similar in the LA and
      OA groups (p > 0.05). Patients with LA had a significantly shorter LOS than OA by
      1.6 days (p < 0.05). This LOS was significantly shorter among those with ruptured
      appendicitis vs. non-ruptured appendicitis (2.0 days vs. 0.3 day reduction, p =
      0.0357). Rank-order multiple regression analysis, controlling for all other
      factors, showed laparoscopy to have a significant effect on postoperative LOS in
      all appendicitis cases, especially ruptured appendicitis. CONCLUSIONS: The two
      day reduction in LOS among those with ruptured appendicitis who underwent LA was
      significant enough to overcome the smaller benefit of LA in acute appendicitis.
      From a hospital utilization point of view, LA should be considered as the first
      line approach for all patients with appendicitis.

PMID- 16437275
TI  - Validation of a new basic virtual reality simulator for training of basic
      endoscopic skills: the SIMENDO.
AB  - BACKGROUND: The aim of this study was to establish content, face, concurrent, and
      the first step of construct validity of a new simulator, the SIMENDO, in order to
      determine its usefulness for training basic endoscopic skills. METHODS: The
      validation started with an explanation of the goals, content, and features of the
      simulator (content validity). Then, participants from eight different medical
      centers consisting of experts (> or =100 laparoscopic procedures performed) and
      surgical trainees (<100) were informed of the goals and received a "hands-on
      tour" of the virtual reality (VR) trainer. Subsequently, they were asked to
      answer 28 structured questions about the simulator (face validity). Ratings were
      scored on a scale from 1 (very bad/useless) to 5 (excellent/very useful).
      Additional comments could be given as well. Furthermore, two experiments were
      conducted. In experiment 1, aimed at establishing concurrent validity, the
      training effect of a single-handed hand-eye coordination task in the simulator
      was compared with a similar task in a conventional box trainer and with the
      performance of a control group that received no training. In experiment 2 (first
      step of construct validity), the total score of task time, collisions, and path
      length of three consecutive runs in the simulator was compared between experts
      (>100 endoscopic procedures) and novices (no experience). RESULTS: A total of 75
      participants (36 expert surgeons and 39 surgical trainees) filled out the
      questionnaire. Usefulness of tasks, features, and movement realism were scored
      between a mean value of 3.3 for depth perception and 4.3 for appreciation of
      training with the instrument. There were no significant differences between the
      mean values of the scores given by the experts and surgical trainees. In response
      to statements, 81% considered this VR trainer generally useful for training
      endoscopic techniques to residents, and 83% agreed that the simulator was useful
      to train hand-eye coordination. In experiment 1, the training effect for the
      single-handed task showed no significant difference between the conventional
      trainer and the VR simulator (concurrent validity). In experiment 2, experts
      scored significantly better than novices on all parameters used (construct
      validity). CONCLUSION: Content, face, and concurrent validity of the SIMENDO is
      established. The simulator is considered useful for training eye-hand
      coordination for endoscopic surgery. The evaluated task could discriminate
      between the skills of experienced surgeons and novices, giving the first
      indication of construct validity.

PMID- 16437276
TI  - Implantable gastric stimulation to achieve weight loss in patients with a low
      body mass index: early clinical trial results.
AB  - This report describes the authors' early outcomes with implantable gastric
      stimulation (IGS) used to achieve weight loss in patients with a low body mass
      index (BMI). After prescreening of potential candidates with a selection
      algorithm, 24 patients (21 women and 3 men) with a low BMI (30-34.9) underwent
      IGS implantation at two centers. The patients had a mean age of 43 years (range,
      32-60 years), a mean BMI of 33 (range, 30-36), and a mean weight of 92 kg (range,
      80-117 kg). At this writing, 6 months postoperatively, there have been no serious
      adverse events related to the device. The mean percentage of excess weight loss
      (EWL) was 5.9%, with three patients explanted because of noncompliance. The mean
      waist circumference decreased 5.8%, which was significant (p = 0.009). A subset
      of nine patients (37.5%) had an EWL exceeding 10% (mean, 20.1%). A subset of low
      BMI patients lost a clinically significant amount of weight with IGS within 6
      months. Further study is required for better identification of potential
      candidates for this novel approach.

PMID- 16437277
TI  - Laparoscopic treatment of nonparasitic hepatic cysts.
AB  - BACKGROUND: We present our experience with laparoscopic deroofing of nonparasitic
      hepatic cysts. METHODS: Laparoscopic deroofing was performed due to a solitary
      hepatic cyst in 21 patients and polycystic liver in four patients. Laparoscopy
      was indicated when a cyst was larger than 5 cm (the general size of cysts was 6.9
      cm) and caused complaints and was in a superficial position. In eight patients in
      whom the cyst was larger than 10 cm, omentoplasty was performed. RESULTS:
      Intraoperative complications were not detected. Two conversions were performed
      because of the deep position of the cyst. Postoperative bile leakage was detected
      in one case that was treated conservatively. The average hospital stay was 4.7
      days. Relapse occurred in two patients (8%), but only one of them required a
      second operation. CONCLUSIONS: We recommend laparoscopic deroofing for treatment
      of nonparasitic liver cysts. This operation causes only slight discomfort for the
      patients, the intra- and postoperative morbidity is low, and relapses are rare.

PMID- 16437278
TI  - Laparoscopic repair of postoperative perineal hernia.
AB  - BACKGROUND: Perineal hernia is an uncommon complication following
      abdominoperineal resection of the rectum. There are only a few reports concerning
      the management of this unusual problem. Various methods of repair have been
      described, but none of them is well established. The purpose of our study is to
      present our experience and to discuss the pathogenesis and the different surgical
      repair techniques of these hernias. METHODS: Between September 2003 and December
      2004, four patients with perineal hernia observed several months following
      laparoscopic abdominoperineal resection for adenocarcinoma of the lower rectum
      were treated. All patients underwent the transabdominal laparoscopic approach
      using synthetic mesh for repair. RESULTS: In all patients, the hernia was
      repaired by the laparoscopic transabdominal approach using synthetic mesh. The
      blood loss was minimal and mean operating time was 54 +/- 10 min. There were no
      cases that required conversion to laparotomy and there were no intraoperative or
      postoperative complications. Beginning of soft diet intake and ambulation times
      were on the second day following surgery. The average length of hospital stay was
      4 +/- 1 days. During 8.3 +/- 6 months of follow-up, there was no recurrence of
      the hernia. CONCLUSION: Perineal hernias are rare complications of major pelvic
      surgeries. Symptomatic hernias should be repaired surgically. The transabdominal
      laparoscopic approach using synthetic mesh provides an appropriate solution for
      these hernias.

PMID- 16437279
TI  - Endoscopic full-thickness resection of the stomach: an experimental approach.
AB  - BACKGROUND: Endoluminal endoscopic resections of the gastrointestinal (GI) tract
      have had increasing significance in recent years. Except for the extraperitoneal
      part of the rectum, endoscopic resections are restricted to the mucosal and
      submucosal layer to preserve the integrity of the GI tract wall. METHODS: The
      SurgAssist is the first flexible stapling device consisting of a 2,000-mm-long
      flexible shaft and a stapling magazine that can be positioned intraluminally and
      used with a remote control. To prove the principle, we investigated the
      endoluminal application of an endoscopically assisted and intraluminally
      visualized full-thickness resection of the gastric wall in a pilot study of three
      pigs and a series of three human exenterates. RESULTS: Full-thickness resection
      of the gastric wall in pigs can be performed with the SurgAssist flexible
      stapling device from an endoluminal access. However, due to the small lumen of
      the esophagus, the simultaneous transesophageal introduction of the stapler shaft
      and gastroscope is not possible in pigs. The same procedure in three human
      exenterates showed that the simultaneous introduction of the flexible stapler and
      a standard gastroscope could be achieved without damaging the esophageal wall.
      Full-thickness resections of up to 4 x 4 cm were carried out with the use of two
      or three stapler magazines. The resulting sutures were found to be airtight upon
      endoscopic inflation of the stomach. CONCLUSION: The clinical use of the
      SurgAssist intraluminal stapling device for endoscopic full-thickness resection
      of the gastric wall seems applicable for lesions in suitable locations of the
      stomach. Gastrointestinal stroma tumors and T1 tumors of the lower gastric corpus
      and antrum region are possible indications.

PMID- 16437280
TI  - The useful combination of a higher frequency miniprobe and endoscopic submucosal
      dissection for the treatment of T1 esophageal cancer.
AB  - BACKGROUND: There are few published data on the discrimination ability of
      endoscopic ultrasonography (EUS) among each subdivision of T1 cancer, and
      overdiagnosis is an unsolved problem that eventually causes overtreatment. The
      purpose of this study was to verify whether our treatment strategy incorporating
      EUS realizes a tailored patient management of T1 esophageal cancer. METHODS: This
      study comprised 20 esophageal cancer patients undergoing 12- to 20-MHz miniprobes
      for T staging and a 7.5-MHz dedicated echoendoscope for N staging. Initial
      therapy constituted endoscopic submucosal dissection (ESD) for
      endosonographically node-negative, mucosal, or slight submucosal cancers and a
      primary esophagectomy with three-field lymphadenectomy for deeper cancers. If the
      ESD specimen revealed no cancer involvement of the muscularis mucosa, the
      patients entered a follow-up program; otherwise, they were advised to undergo a
      subsequent esophagectomy and three-field lymphadenectomy. RESULTS: Perfect
      discrimination accuracy was achieved among T1, T2, and T3 cancers. Whether cancer
      depth was up to the slight submucosal layer or deeper was correctly
      differentiated in 12 of 14 T1 cancers (86%). EUS categorized all patients
      correctly into candidates for either ESD or surgery. The pathological cancer
      depth of the resected specimens revealed that no patients experienced unnecessary
      overtreatment. CONCLUSIONS: A higher frequency miniprobe is useful for the
      detailed evaluation of cancer depth, contributing to decision making for
      treatment options of T1 esophageal cancer. A miniprobe and echoendoscope in
      combination with ESD provide an appropriately tailored management plan on an
      individual basis, avoiding unnecessary treatment or indicating radical surgery.

PMID- 16437281
TI  - Heller myotomy vs Heller myotomy plus Dor fundoplication: cost-utility analysis
      of a randomized trial.
AB  - BACKGROUND: The addition of a Dor antireflux procedure reduces the risk of
      pathologic gastroesophageal reflux (GER) by ninefold following laparoscopic
      Heller myotomy for achalasia. It is not clear, however, how these benefits
      compare with the increased cost of the fundoplication. The objective of this
      study was to estimate the cost-effectiveness of Heller myotomy plus Dor
      fundoplication compared with Heller alone in patients with achalasia. METHODS: We
      conducted a cost-utility analysis using the Markov simulation model to examine
      the two treatment alternatives. The model estimated the total expected costs of
      each strategy over a 10-year time horizon. Data for the model were derived from
      our randomized clinical trial. The strategies were compared using the method of
      incremental cost-effectiveness analysis. RESULTS: The incidence of pathologic GER
      was 47.6% (10 of 21 patients) in the Heller group and 9.1% (2 of 22 patients) in
      the Heller plus Dor group using an intention-to-treat analysis (p = 0.005).
      Heller plus Dor was associated with a significant reduction in the risk of GERD
      (relative risk 0.11; 95% confidence interval 0.02-0.59; p = 0.01). The cost of
      surgery was significantly higher for Heller plus Dor than for Heller alone (mean
      difference $942; p = 0.04), secondary to a longer operating room time (mean
      difference 40 min; p = 0.01). At a time horizon of 10 years, when proton pump
      inhibitor (PPI) therapy costs are considered, the cost-utility analysis
      demonstrates that Heller plus Dor surgery is associated with a total cost of
      $6,861 per patient and a quality-adjusted life expectancy of 9.9 years, whereas
      Heller-alone surgery is associated with a cost of $9,541 per patient and a
      quality-adjusted life expectancy of 9.5 years. CONCLUSIONS: In achalasia
      patients, Heller myotomy plus Dor fundoplication is preferred to Heller alone
      because it is both more effective in preventing postoperative GERD and more cost
      effective at a time horizon of 10 years.

PMID- 16437282
TI  - Minimal access adrenal surgery.
AB  - Laparoscopic adrenalectomy has become the preferred method for removal of most
      adrenal tumors. An important component in selecting patients for this operation
      is to understand the clinical presentation and diagnostic workup for the various
      functioning and nonfunctioning adrenal tumors. In this review, an overview of the
      key clinical and diagnostic aspects of the most common adrenal tumors is
      presented. The indications and contraindications for a laparoscopic approach are
      discussed and the technique for laparoscopic adrenalectomy is then presented with
      inclusion of video links to demonstrate the technique. A review of the results of
      laparoscopic adrenalectomy is then considered with regard to common outcome
      measures and complications. A current controversy in adrenal surgery is the role
      of laparoscopic adrenalectomy in the management of patients with large tumors and
      malignant or potentially malignant adrenal lesions and the literature on this
      topic is reviewed in detail. The article concludes with a discussion of the
      indications and technique for partial adrenalectomy.

PMID- 16437283
TI  - Minilaparotomy cholecystectomy versus laparoscopic cholecystectomy: a randomized
      study with special reference to obesity.
AB  - BACKGROUND: Minilaparotomy cholecystectomy (MC) has recently challenged the role
      of the laparoscopic approach (LC) for cholecystectomies. However, the situation
      is far from clear when operating times and recovery are evaluated. METHODS:
      Altogether 157 patients with uncomplicated symptomatic gallstones were randomized
      into MC (n = 85) and LC (n = 72) groups. Both groups were similar in terms of
      age, body mass index, American Society of Anesthesiology (ASA) physical fitness
      classification, and operating surgeon. RESULTS: The mean operating time was 55 +/
      19.5 min in the MC group and 79 +/- 27.0 min in the LC group (p < 0.0001). The
      postoperative hospital stay and length of sick leave did not differ between the
      two groups. There were no significant differences in postoperative pain,
      analgesic consumption, or postoperative pulmonary function between the groups.
      The body mass index did not influence operating time or patient recovery in
      either group. No major complications occurred in either groups. CONCLUSION: The
      MC procedure seems to be a faster technique than the LC approach for
      noncomplicated gallstone disease, with no difference in recovery times. The MC
      procedure also seems to be suitable for the obese patient.

PMID- 16437284
TI  - Systematic evaluation of different approaches for minimizing hemodynamic changes
      during pneumoperitoneum.
AB  - BACKGROUND: Capnoperitoneum (CP) compromises hemodynamic function during
      laparoscopy. Three therapeutic concepts were evaluated with an aim to minimize
      the hemodynamic reaction to CP: First, a controlled increase of intrathoracic
      blood volume (ITBV) by intravenous fluids; second, partially reduced sympathetic
      activity by the beta1-blocker esmolol; and third, a decrease in mean arterial
      pressure (MAP) by the vasodilator sodium nitroprusside. METHODS: For this study,
      43 pigs were assigned to treatment with fluid and sodium nitroprusside (group A)
      or with esmolol (group B). In both groups, the pigs were assigned to head-up,
      head-down, or supine position, resulting in three different subgroups. Invasive
      hemodynamic monitoring was established including left heart catheter and cardiac
      oxygen lung water determination (COLD) measurements. Measurements were documented
      before CP with the animals in supine position, after induction of a 14-mmHg CP
      with the animals in each body position, after a 10% reduction in MAP by
      vasodilation, and after an increase in ITBV of about 30% by infusion of 6%
      hydroxyethylstarch solution. RESULTS: Increasing ITBV improved hemodynamic
      function in all body positions during CP. Esmolol reduced cardiac output and
      myocardial contractility. Sodium nitroprusside did not improve hemodynamic
      function in any body position. CONCLUSIONS: Optimizing volume load is effective
      for minimizing hemodynamic changes during CP in the head-up and in head-down
      positions. In general, beta(1)-blockers cannot be recommended because they might
      additionally compromise myocardial contractility and suppress compensatory
      reaction of the sympathetic nerve system. Vasodilation has not improved
      hemodynamic parameters during CP.

PMID- 16437285
TI  - Carbon dioxide differentially affects the cytokine release of macrophage
      subpopulations exclusively via alteration of extracellular pH.
AB  - BACKGROUND: The improved outcome after endoscopic surgery has been attributed to
      less surgical trauma. However, the underlying mechanisms are not fully
      understood, and direct effects of CO2 used for pneumoperitoneum, cellular
      acidification, and/or the lack of air contamination have been postulated to
      additionally modulate immune functions during endoscopic surgery. We investigated
      the effects of CO2 incubation, extracellular acidification, and air contamination
      on the inflammatory response of two distinct macrophage populations. METHODS: R2
      and NR 8383 rat macrophage cell lines were used. Interleukin-6 (IL-6) and nitric
      oxide after lipopolysaccharide (LPS) stimulation were determined in these sets of
      experiments: incubation in 100% CO2, 5% CO2, and room air for 2h; incubation at
      pH 7.4, 6.5, and 5.5 for 2 h in 5% CO2; and incubation in 100% CO2, 5% CO2 and
      room air in fixed pH 6.3. The extracellular pH was monitored during incubation.
      We determined the alteration of intracellular pH in cells subjected to
      extracellular acidification by fluorescence microscopy. RESULTS: Extracellular pH
      decreased to 6.3 during 100% CO2 incubation. IL-6 release was reduced after CO2
      incubation in NR 8383 cells and increased in R2 cells (p < 0.05). It was not
      altered by air incubation. Decreasing the extracellular pH to 6.5 mimicked the
      effects of CO2 and a decrease to 5.5 suppressed IL-6 release in both cell lines.
      In fixed pH at 6.3, CO2 and air incubation had no effect. CO2 and pH had no
      impact on nitric oxide release and vitality. Intracellular pH decreased with
      extracellular acidification without significant difference between the two cell
      lines. CONCLUSIONS: A decrease in extracellular pH during incubation in CO2
      differentially affects IL-6 release in macrophage subpopulations. This may
      explain contradictory results in the literature. Moreover, we demonstrated that
      air contamination does not affect macrophage cytokine release. The decrease in
      extracellular pH is the primary underlying mechanism of the alteration of
      macrophage cytokine release after CO2 incubation, and it appears that the ability
      to maintain intracellular pH is not determined by the effects of CO2 or
      extracellular acidification.

PMID- 16437286
TI  - Optimization of reading conditions for flat panel displays.
AB  - Task Group 18 (TG 18) of the American Association of Physicists in Medicine has
      developed guidelines for Assessment of Display Performance for Medical Imaging
      Systems. In this document, a method for determination of the maximum room
      lighting for displays is suggested. It is based on luminance measurements of a
      black target displayed on each display device at different room illuminance
      levels. Linear extrapolation of the above luminance measurements vs. room
      illuminance allows one to determine diffuse and specular reflection coefficients.
      TG 18 guidelines have established recommended maximum room lighting. It is based
      on the characterization of the display by its minimum and maximum luminance and
      the description of room by diffuse and specular coefficients. We carried out
      these luminance measurements for three selected displays to determine their
      optimum viewing conditions: one cathode ray tube and two flat panels. We found
      some problems with the application of the TG 18 guidelines to optimize viewing
      conditions for IBM T221 flat panels. Introduction of the requirement for minimum
      room illuminance allows a more accurate determination of the optimal viewing
      conditions (maximum and minimum room illuminance) for IBM flat panels. It also
      addresses the possible loss of contrast in medical images on flat panel displays
      because of the effect of nonlinearity in the dependence of luminance on room
      illuminance at low room lighting.

PMID- 16437287
TI  - Improved strategy for comparing microbial assemblage fingerprints.
AB  - Microbial fingerprinting techniques permit the rapid visualization of entire
      assemblages in single assays, allowing direct comparison of communities in
      different samples, where the null hypothesis of such analyses is that all samples
      are the same. The comparison of fingerprints relies upon the precise estimation
      of all amplified DNA fragment lengths, which correspond to operational taxonomic
      units (OTU; analogous, but not equal to, a taxon in macroorganism studies).
      However, computer interpolation of size standards (and consequently OTU size
      calling) can be imprecise between gel runs, which can lead to imprecise
      calculation of similarity indices between multiple assemblages. To account for
      OTU size calling imprecision, all fragments within a range of sizes (a window)
      can be combined (i.e., "binned") where the window is as wide as the imprecision
      of OTU size calling. However, artifacts may occur upon binning samples that may
      cause samples to appear less similar to each other, caused by splitting of OTU
      between adjacent bin windows. In this work we present an improved binning
      technique that accounts for OTU size calling imprecision in the comparison of
      multiple fingerprints. This technique comprises binning all pairwise comparisons
      in multiple bin window frames, where the starting size of the window (i.e.,
      frame) is shifted by +1 bp for a total of x frames, where x bp is the width of
      the maximum bin window size in any binning scheme. Pairwise similarity indices
      between different community fingerprints are calculated for each of the x frames.
      To best address the null hypothesis of the community comparison, the maximum
      similarity value of all x frames is then used in downstream analyses to compare
      the communities. We believe this binning technique provides the most accurate and
      least biased comparison between different microbial fingerprints.

PMID- 16437288
TI  - Comparison of the EEG-based SNAP index and the Bispectral (BIS) index during
      sevoflurane-nitrous oxide anaesthesia.
AB  - The BIS monitor (Aspect Medical Inc, Newton, USA) was the first
      electroencephalogram (EEG)-based monitor of the hypnotic effect reflected by a
      dimensionless figure ranging from 100 (awake state) to 0 (flat line EEG). Its
      widespread use makes it the most-studied and the best-known among same intended
      devices. Its algorithm processes low-frequency EEG oscillations in order to
      provide the Bispectral index. A BIS index ranging from 40 to 60 has been
      established as the proper for surgical performance. The BIS monitor permits a
      closer approach to the hypnotic component of anaesthesia beyond clinical signs
      and may reduce the probability of intraoperative awareness; therefore, it has
      become a recommended monitoring tool in routine practice. The SNAP monitor
      (Nicolet Biomedical, Madison WI, USA) is also intended for monitoring the
      hypnotic effect of anaesthetics, which is in turn displayed as an index ranging
      from 100 to 0, with 100 meaning a fully awake state and 0 meaning no brain
      activity. The algorithm of the SNAP monitor is featured by its additional
      processing of ultra-high EEG frequencies, which seem to be involved in the
      formation of consciousness. The use of these frequencies would theoretically
      improve responsiveness during increased brain activity. We studied its behaviour
      patterns and capability to monitor the hypnotic effect induced by sevoflurane
      nitrous oxide by comparison with the BIS index. Seventy patients ASA I-III were
      induced with propofol, fentanyl and rocuronium, and maintained with sevoflurane
      N(2)O. BIS and SNAP indices were simultaneously recorded before induction, after
      intubation, after incision, at the following 10, 30 and 50 minutes, awakening and
      extubation time points, together with heart rate and blood pressure. The Pearson
      correlation was R(2) = 0.68 (p < .05). The Bland and Altman test showed a bias of
      14.3 for SNAP index values with respect to BIS index values. We concluded that
      the SNAP index correlates with variations in the hypnotic effect induced by
      sevoflurane-nitrous oxide anaesthesia when compared with the BIS index. In this
      context, a SNAP index ranging from 58 to 70 would be equivalent to the BIS index
      range 40 to 60 and, therefore, the accurate for surgical performance.

PMID- 16437289
TI  - BIS monitor findings during self-hypnosis.
AB  - OBJECTIVE: We describe BIS values for a patient undergoing breast surgery under
      self-hypnosis in order to access the value of global surface EEG measures
      occurring during this process. METHODS: Following verbal consent, a BIS(TM)
      monitor (Aspect Medical, Newton MA) was placed and values measured while the
      patient performed self-hypnosis for a simple mastectomy and sentinel node biopsy.
      RESULTS: Thirty-nine minutes after incision the BIS value decreased transiently
      to 72 followed by several other transient decreases, the lowest of which was 59.
      Values remained at approximately 90 throughout most of the operative period. The
      BIS value returned to baseline after completion of the operation. CONCLUSIONS:
      Our findings support the hypothesis that hypnosis is a dynamic cerebral process
      incorporating many changes within brain activation centers and one distinct from
      dissociative patterns seen under anesthesia. Current algorithms employed by the
      BIS(TM) monitor add little to the management of patients utilizing hypnosis for
      analgesia.

PMID- 16437290
TI  - Cardiac output measurement by pulse dye densitometry: comparison with pulmonary
      artery thermodilution in post-cardiac surgery patients.
AB  - OBJECTIVE: Pulse-dye densitometry (PDD) could be a suitable, low-invasive
      alternative to thermodilution using a pulmonary artery catheter (PAC) for
      monitoring cardiac output. The aim of our study was to assess the reproducibility
      and validity of PDD compared to PAC-thermodilution. METHODS: In 43 post-cardiac
      surgery patients, the mean of triplicate readings of cardiac output was assessed
      using both methods. In a subgroup of 26 patients, a second set of measurements
      was obtained on average 2 h later. RESULTS: Reproducibility of consecutive
      measurements was slightly better for PAC-thermodilution than for PDD (median
      coefficient of variation of the triplicate measurements: 3.5% versus 5.4%, P <
      0.01). Both methods correlated well (r = 0.84, p < 0.001). Using Bland and Altman
      analyses with PAC-thermodilution as the reference method, PDD showed a bias of 
      0.68 +/- 0.82 L/min, mainly due to differences in higher ranges of cardiac output
      (>6.5 L/min). Measured changes in cardiac output were 81% concordant (i.e. <1
      L/min different) between both methods. CONCLUSION: PDD correlates well with PAC
      thermodilution and thus deserves consideration as a low-invasive alternative for
      measurement and follow-up of cardiac output.

PMID- 16437291
TI  - Tutorial on univariate autoregressive spectral analysis.
AB  - In the present paper, the theoretical basis of autoregressive (AR) modelling in
      spectral analysis is explained in simple terms. Spectral analysis gives
      information about the frequency content and sources of variation in a time
      series. The AR method is an alternative to discrete Fourier transform, and the
      method of choice for high-resolution spectral estimation of a short time series.
      In biomedical engineering, AR modelling is used especially in the spectral
      analysis of heart rate variability and electroencephalogram tracings. In AR
      modelling, each value of a time series is regressed on its past values. The
      number of past values used is called the model order. An AR model or process may
      be used in either process synthesis or process analysis, each of which can be
      regarded as a filter. The AR analysis filter divides the time series into two
      additive components, the predictable time series and the prediction error
      sequence. When the prediction error sequence has been separated from the modelled
      time series, the AR model can be inverted, and the prediction error sequence can
      be regarded as an input and the measured time series as an output to the AR
      synthesis filter. When a time series passes through a filter, its amplitudes of
      frequencies are rescaled. The properties of the AR synthesis filter are used to
      determine the amplitude and frequency of the different components of a time
      series. Heart rate variability data are here used to illustrate the method of AR
      spectral analysis. Some basic definitions of discrete-time signals, necessary for
      understanding of the content of the paper, are also presented.

PMID- 16437292
TI  - Analysis of nighttime activity and daytime pain in patients with chronic back
      pain using a self-organizing map neural network.
AB  - There may be a relationship between sleep and pain in patients with chronic back
      pain. We collected day-time pain and nighttime activity data from 18 patients
      diagnosed with chronic back pain. The patients were followed for 6 days and 5
      nights. Pain levels were collected every 90 min between 0800 hours and 2,200
      hours using a computerized electronic diary. Activity levels were collected using
      a wrist accelerometer (Actiwatch AW-64). The Actiwatch sampled activity counts
      every 1 min. Patients were asked to wear the Actiwatch on their non-dominant arm.
      The pain level measurements were interpolated using cubic splines. A mean pain
      level was calculated for each period 0800 hours to 2,200 hours as well as for the
      6-day period. The difference between the mean pain levels for the 6-day period
      and each 0800 hours to 2,200 hours period was calculated for each patient.
      Nighttime activity data were analyzed using the Actiwatch Sleep Analysis
      software. Correlations were calculated between the Actiwatch Sleep Analysis
      variables and the mean pain level differences for each patient and period. The
      correlation analysis was performed with SPSS 7.5. We were unable to show any
      significant relationships.A different approach to analyze the data was used. A
      Self-Organizing Map (SOM) Neural Network was trained using the original nighttime
      activity level time series from 10 randomly selected patients. Recall was then
      performed on all the activity level data. Correlations were calculated between
      the pain level variance for the 6-day period for each patient and the
      corresponding difference in the SOM output coordinates. The correlation was found
      to be r = 0.73, p < 0.01). We conclude that daytime pain levels are not directly
      correlated with sleep in the following night and that sleep is not directly
      correlated with daytime pain levels on the following day in this group of
      patients. There appears to be a correlation between the difference in nighttime
      activity levels and patterns and the daytime pain variance. Patients who
      experience large fluctuations in daytime pain levels also show a higher
      variability in their nighttime activity levels and patterns. Even though we were
      unable to show a direct relationship between daytime pain and sleep, it may be
      reasonable to assume that better pain control resulting in less daytime pain
      fluctuations can provide more stable nighttime activity levels and patterns in
      this limited group of patients. By using a neural network model, we were able to
      extract information from the nighttime activity levels even though a traditional
      statistical analysis was unsuccessful.

PMID- 16437293
TI  - A mathematical model of differential tracheal tube cuff pressure: effects of
      diffusion and temperature.
AB  - The tracheal tube cuff performs an important function during anesthesia and
      critical care situations by allowing positive pressure ventilation and isolating
      the lungs from aspiration. Other maneuvers, such as pressure support ventilation
      and positive end-expiratory pressure, are also cuff-dependent. However, excessive
      cuff pressure, as well as long-term intubation without excessive cuff pressure,
      have been associated with significant morbidity and mortality. A straightforward
      mathematical model of differential tracheal tube cuff pressure has been
      developed. This model incorporates compliance, temperature variation, and net
      molar diffusion in determining differential tracheal tube cuff pressure. In
      addition, temperature and diffusion are modeled as separate processes which
      effect differential cuff pressure independently. Support for the validity of this
      model is based upon an analysis of existing data from prior studies.

PMID- 16437294
TI  - Applying the ISO/IEEE 11073 standards to wearable home health monitoring systems.
AB  - OBJECTIVE: The goal of this effort was to investigate the feasibility of applying
      the ISO/IEEE 11073 (a.k.a. X73) standards, originally intended for bedside
      monitoring in hospital environments, to wearable, multi-sensor monitoring systems
      designed for home healthcare. METHODS: The X73 upper-layer sub-standards (i.e.,
      nomenclature specification, domain information model, application profiles, and
      vital sign device descriptions) were adopted and implemented on microcontroller
      based sensor hardware to provide plug-and-play medical components. Three types of
      system elements (base stations, data loggers, and sensor units) perform the
      functionality required in this standards-based home health monitoring system and
      communicate using Bluetooth wireless modules. The base station incorporates a
      LabVIEW interface running on a personal computer. Each data logger and sensor
      unit is implemented on a microcontroller-driven embedded platform. Sensor units
      include wearable sensors (e.g., electrocardiograph, pulse oximeter) and nearby
      sensors (e.g., weight scale, ambient environment sensors). RESULTS: The standards
      based prototype system with an open architecture achieves plug-and-play
      performance suitable for a home environment. Each wireless element in the
      body/home area network can automatically detect other nearby devices, associate
      with them, and exchange data with them as appropriate. CONCLUSIONS: With minor
      modifications, the X73 standards can be successfully applied to wearable,
      wireless, point-of-care systems in the home.

PMID- 16437297
TI  - Characterization of interstitial cells of Cajal in bowel of cattle (Bos taurus).
AB  - Interstitial cells of Cajal (ICC) have been described in the gastrointestinal
      tract of different mammals including humans, horses, pigs, rats, dogs, mice and
      guinea-pigs. In the present study, ICC were identified in the jejunum of Bos
      taurus using polyclonal anti-c-Kit antibodies in immunohistochemical assays.
      Vimentin and desmin intermediate filaments were also determined using monoclonal
      antibodies. ICC were found in the tunica muscularis either in a palisade
      distribution pattern between the outer longitudinal and the inner circular layers
      (ICC-MP) or freely distributed in clusters in the longitudinal layer (ICC-LM).
      Morphometric studies determined that ICC have a fusiform shape presenting
      cytoplasmic prolongations. ICC were positive to c-Kit and vimentin antigens but
      negative to desmin. We have observed and described for the first time the
      presence of ICC in a ruminant. As observed in the aforementioned mammals, bovine
      ICC were associated with the myenteric plexus. Nevertheless, the presence of
      widespread ICC in the longitudinal muscular layer of the jejunum differs from
      previously described studies of other mammals.

PMID- 16437295
TI  - Intraoperative monitoring of segmental spinal nerve root function with free-run
      and electrically-triggered electromyography and spinal cord function with
      reflexes and F-responses. A position statement by the American Society of
      Neurophysiological Monitoring.
AB  - BACKGROUND CONTEXT: Orthodromic ascending somatosensory evoked potentials and
      antidromic descending neurogenic somatosensory evoked potentials monitor spinal
      cord sensory function. Transcranial motor stimulation monitors spinal cord motor
      function but only activates 4-5% of the motor units innervating a muscle.
      Therefore, 95-96% of the motor spinal cord systems activating the motor units are
      not monitored. To provide more comprehensive monitoring, 11 techniques have been
      developed to monitor motor nerve root and spinal cord motor function. These
      techniques include: 1. neuromuscular junction monitoring, 2. recording free-run
      electromyography (EMG) for monitoring segmental spinal nerve root function, 3.
      electrical stimulation to help determine the correct placement of pedicle screws,
      4. electrical impedance testing to help determine the correct placement of
      pedicle screws, 5. electrical stimulation of motor spinal nerve roots, 6.
      electrical stimulation to help determine the correct placement of iliosacral
      screws, 7. recording H-reflexes, 8. recording F-responses, 9. recording the
      sacral reflex, 10. recording intralimb and interlimb reflexes and 11. recording
      monosynaptic and polysynaptic reflexes during dorsal root rhizotomy. OBJECTIVE:
      This paper is the position statement of the American Society of
      Neurophysiological Monitoring. It is the practice guideline for the
      intraoperative use of these 11 techniques. METHODS: This statement is based on
      information presented at scientific meetings, published in the current scientific
      and clinical literature, and presented in previously-published guidelines and
      position statements of various clinical societies. RESULTS: These 11 techniques
      when used in conjunction with somatosensory and transcranial motor evoked
      potentials provide a multiple-systems approach to spinal cord and nerve root
      monitoring. CONCLUSIONS: The techniques reviewed in this paper may be helpful to
      those wishing to incorporate these techniques into their monitoring program.

PMID- 16437298
TI  - Serological confirmation of Borrelia burgdorferi infection in dogs in the Czech
      Republic.
AB  - From the epidemiological point of view, dogs are very important since they are
      considered a suitable indicator of the spread of human borreliosis. Serum samples
      obtained from healthy, asymptomatic military dogs from 12 different areas in the
      Czech Republic were examined for IgG antibodies to Borrelia burgdorferi sensu
      lato (s.l.). The total of 399 serum samples were tested by a whole-cell ELISA.
      Specific antibodies to Borrelia burgdorferi s.l. were detected in 26 cases
      (6.5%). In different localities, the seroprevalence varied from 0.0% to 28.6%.
      Two local isolated strains Br-75 (Borrelia afzelii) and Br-97 (Borrelia garinii)
      were used as antigens. A total of 22 (5.5%) were positive for antibodies to
      Borrelia afzelii and 19 (4.8%) were positive for antibodies to Borrelia garinii.
      Fifteen cases were positive for both antibodies. A significantly higher
      seroprevalence was found in younger dogs (1-3 years) than in older ones (p <
      0.05). An analysis of seroprevalence by months of sampling showed no significant
      difference (p > 0.05).

PMID- 16437299
TI  - A multiplex PCR to identify porcine mycoplasmas present in broth cultures.
AB  - Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Mycoplasma flocculare can be
      present in the lungs of pigs at the same time. These three mycoplasma species all
      require similar growth conditions and can be recovered from clinical samples
      using the same media. We have developed a multiplex PCR as a helpful tool for
      rapid differentiation of these three species in the course of isolation. Based on
      the 16S ribosomal DNA sequences, three different forward primers and a single
      reverse primer were selected. Each forward primer was compared to available
      mycoplasma sequences, showing the primers to be specific. The three amplification
      products observed of 1129 bp (M. hyorhinis), 1000 bp (M. hyopneumoniae) and 754
      bp (M. flocculare) were clearly distinguishable on a 1% agarose gel. In addition,
      no cross-reaction with Mycoplasma hyosynoviae, another porcine mycoplasma, was
      noted. This multiplex PCR using the proposed set of primers is the first reported
      assay that allows the simultaneous identification of the different Mycoplasma
      species isolated from the lungs of pigs.

PMID- 16437300
TI  - Erythrocyte lipid peroxides and blood zinc and copper concentrations in acute
      undifferentiated diarrhoea in calves.
AB  - Undifferentiated acute calf diarrhoea is a major concern for the dairy industry
      and its aetiopathogenesis remains diverse. The present study aimed to examine the
      role of oxidative stress through estimation of erythrocyte lipid peroxide levels
      and blood zinc and copper concentrations using natural cases of diarrhoea in
      calves aged 15-30 days old. The calves were kept under identical managemental
      conditions and were provided with pooled whole colostrum during the first three
      days and thereafter with only whole milk until they were 1 month old. Diarrhoeic
      (n = 11) and normal calves (n = 11) of the same age group (15-30 days old) were
      randomly selected from an organized dairy farm for the study. The mean blood zinc
      concentration (50.01+/-2.45 mumol/L vs 66.06+/-3.06 mumol/L) was significantly (p
      < 0.05) lower and copper concentration was significantly (p < 0.05) higher in
      diarrhoeic calves (12.90+/-0.31 mumol/L vs. 9.44+/-0.16 mumol/L) than in the
      healthy calves. The erythrocyte lipid peroxides level was higher (p < 0.05) in
      diarrhoeic calves (6.88+/-0.23 nmol malondialdehyde (MDA) per mg of haemoglobin
      (Hb)) than healthy calves (6.27+/-0.07 nmol MDA per mg Hb). From the results of
      the study it is concluded that oxidative stress and antioxidant minerals (zinc
      and copper) might play important roles in the aetiopathogenesis of bovine calf
      diarrhoea.

PMID- 16437301
TI  - Evaluation of fungicidal efficacy of benzalkonium chloride (Steramina G u.v.) and
      Virkon-S against Microsporum canis for environmental disinfection.
AB  - The aim of this study is to evaluate the antifungal efficacy of Steramina G u.v.
      (10% solution of alkyldimetylbenzylammonium chloride; Formenti Grunenthal) and
      Virkon-S (multipurpose system; Antec International) against Microsporum canis
      infected hairs and spores. Samples were collected from a random sample of
      household cats and from subjects from catteries. Seventy M. canis-positive
      hairbrushes containing furs, keratin scales and other organic material were
      treated with each of the two disinfectants, using concentrations recommended by
      the manufacturer's instructions (2% and 1% for Steramina G u.v. and Virkon-S,
      respectively). Each brush remained in contact with the antifungal solution for 10
      min. After this period, the brushes were air-dried, then seeded into mycobiotic
      agar, and incubated for up to 21 days at 28 degrees C. The disinfectants were
      considered effective if dermatophytes failed to grow. Steramina G u.v. was
      effective in 97.14% of samples and Virkon-S in 87.14%. The antifungal activity of
      Steramina G u.v. against M. canis was significantly higher (p < 0.05) than that
      of Virkon-S.

PMID- 16437302
TI  - Pharmacokinetics of eprinomectin in plasma and milk following subcutaneous
      administration to lactating dairy cattle.
AB  - Eprinomectin is only available as a topically applied anthelmintic for dairy
      cattle. To determine whether eprinomectin can be applied as an injectable
      formulation in dairy cattle, a novel injectable formulation was developed and was
      subcutaneously delivered to four lactating dairy cattle at a dose rate of 0.2 mg/
      kg. Plasma and milk samples were collected. The concentrations of eprinomectin in
      all samples were determined by HPLC. The peak plasma concentration (C(max))of
      44.0+/-24.2 ng/ml occurred 39+/-19.3 h after subcutaneous administration,
      equivalent to the C(max) (43.76+/-18.23 ng/ml) previously reported for dairy
      cattle after a pour-on administration of 0.5 mg/kg eprinomectin. The area under
      the plasma concentration-time curve (AUC) after subcutaneous administration was
      7354+/-1861 (ng h)/ml, higher than that obtained after pour-on delivery
      (5737.68+/-412.80 (ng h)/ml). The mean residence time (MRT) of the drug in plasma
      was 211+/-55.2 h. Eprinomectin was detected in the milk at the second sampling
      time. The concentration of drug in milk was parallel to that in plasma, with a
      milk to plasma ratio of 0.16+/-0.01. The highest detected concentration of
      eprinomectin in milk was 9.0 ng/ml, below the maximum residue limit (MRL) of
      eprinomectin in milk established by the Joint FAO/WHO Expert Committee on Food
      Additives in 2000. The amount of eprinomectin recovered in the milk during this
      trial was 0.39%+/-0.08% of the total administered dose. This study demonstrates
      that subcutaneous administration of eprinomectin led to higher bioavailability
      and a lower dose than a pour-on application, and that an injectable formulation
      of eprinomectin may be applied in dairy cattle with a zero withdrawal period.

PMID- 16437303
TI  - Comparison of hydrolytic and conjugative biotransformation pathways in horse,
      cattle, pig, broiler chick, rabbit and rat liver subcellullar fractions.
AB  - To complete a studyaimed at investigating the pattern of the basal activities of
      liver xenobioticmetabolizing enzymes in major and minor species intended for meat
      production, microsomal carboxylesterases and some conjugating enzyme activities
      were determined and compared in liver preparations from horses, cattle, pigs,
      rabbits and broiler chicks, using the rat as a reference species. Horses and
      broiler chicks exhibited a lower microsomal carboxylesterase activity towards
      indophenyl or p-nitrophenyl acetate than that measured in cattle or pig
      subfractions. Among food-producing species, the rate of glucuronidation of either
      1-naphthol or p-nitrophenol was in the order pigs approximately rabbits > horses
      >> cattle > broiler chicks. The widest variations were observed in the
      acetylation capacity towards p-aminobenzoic acid or isoniazid, which in rabbits
      was 3-fold to 11-fold greater than that displayed by any other examined species;
      low but measurable activities were found in equine and bovine cytosols. The
      activity of cytosolic glutathione S-transferase (GST) accepting the general
      substrate 1-chloro-2,4-dinitrobenzene was significantly higher in rabbits, horses
      and pigs than in rat, broiler chicks and cattle. Finally, an uneven pattern of
      activity towards the other tested GST substrates - 3,4-dichloronitrobenzene,
      ethacrinic acid or 1,2-epoxybutane - was observed, possibly reflecting the
      species-related expression of different GST classes; in this respect, the
      conjugative capacity displayed by horses was higher than or comparable to that
      found in the other food-producing species.

PMID- 16437304
TI  - Pharmacokinetics of an ampicillin-sulbactam (2:1) combination after intravenous
      and intramuscular administration to chickens.

PMID- 16437305
TI  - Detection of feline calicivirus (FCV) from vaccinated cats and phylogenetic
      analysis of its capsid genes.
AB  - We analysed genogroups of four feline calcivirus (FCV) isolates (FCV-S, H10,
      Ao198-1 and ML89) obtained from cats that experienced FCV infection after having
      been vaccinated against FCV. New PCR primer sets (8F/8R, Ao-S/Ao-A, cp-S/cp-A)
      were also designed, since the conventional Seal primer failed to amplify the
      target sequences in two samples. The genogroups of the four isolates as well as
      eight global and 17 domestic strains were determined by phylogenetic analysis of
      their amino acid sequences. One out of the four strains (25%) isolated in this
      study, H10, was grouped into genogroup I, along with the vaccine strains F9 and
      FCV-255. The other three isolates (75%) belonged to genogroup II. Thus, there
      were more isolates in genogroup II than in genogroup I. However, the antibody
      values of the four isolates against cat anti-F9 antisera were significantly
      decreased. There may be no relationship between the neutralizing antibody titre
      and genogroup. Amino acid sequence alignment of the four isolates showed that
      only a single amino acid in region C, which is involved in neutralization
      epitopes, was different in ML89 strain from that of F9. The other three strains,
      H10, Ao198-1 and FCV-B, shared the same amino acid sequence with F9. Alignment of
      amino acids for linear epitopes in the F9 strain, which are located at regions D
      and E, showed variations in 5' hypervariable region (HVR) of E, whereas D and
      conE had only synonymous substitutions i.e. no change in the amino acid sequence.
      This mutation in 5' HVR of region E suggested a vaccine breakdown, as the region
      is known to be essential for antigenicity. The genogroup II FCV is likely to be
      the cause of the FCV infection in this study, while the vaccine strains belong to
      genogroup I. Thus, the existing vaccine may need reevaluation for its
      effectiveness.

PMID- 16437307
TI  - A simple and rapid method for detection of African horse sickness virus serogroup
      in cell cultures using RT-PCR.

PMID- 16437306
TI  - Feline immunodeficiency virus and puma lentivirus in Florida panthers (Puma
      concolor coryi): epidemiology and diagnostic issues.
AB  - This study documents the seroprevalence of feline immunodeficiency virus (FIV)
      and puma lentivirus (PLV) in free-ranging and captive Florida panthers (Puma
      concolor coryi) (n = 51) and translocated Texas cougars (P. concolor stanleyana)
      (n = 10) from 1985 to 1998. The sera were tested for anti-FIV antibodies by
      enzyme-linked immunosorbent assay (ELISA) and Western blot tests. The ELISAs were
      read kinetically (KELA) and the sera were retrospectively examined by PLV peptide
      ELISA. Eleven panthers and one cougar were positive by KELA; 4 panthers and 4
      cougars were equivocal; 35 panthers and 5 cougars were negative; and 1 panther
      had no data. Seven of the 11 KELA-positive panthers were also positive by Western
      blot tests and all but one were positive by PLV peptide ELISA. Ten KELA-negative
      and Western blot-negative cats, were positive by PLV peptide ELISA. KELA results
      varied within cats from one sample period to the next, but PLV peptide ELISA
      results were consistent. Territorial sympatry and mating behaviour, noted from
      radiotelemetry location data on the cats, may have contributed to viral
      transmission between seropositive animals. These findings suggest that Florida
      panthers and the introduced Texas cougars have been exposed to FIV and/or PLV.

PMID- 16437308
TI  - Comparison of diagnostic efficacy of a monoclonal antibody-based competitive
      ELISA test with a similar commercial test for the detection of antibodies to
      Peste des Petits Ruminants (PPR) virus.

PMID- 16437309
TI  - Can nutraceuticals affect the structure of intestinal mucosa? Qualitative and
      quantitative microanatomy in L-glutamine diet-supplemented weaning piglets.
AB  - Weaning piglets were fed an L-glutamine-supplemented diet with the aim of
      monitoring the effects on gut mucosal turnover and barrier function, to elucidate
      the potential preventive or therapeutic roles of glutamine as a nutraceutical or
      'functional food'. Sixteen female weaning piglets were divided into two groups,
      which were fed a control diet (Ctr group: n = 8) or a Ctr + 0.5% L-glutamine diet
      (G group: n = 8) for 28 days. In the ileum of group G piglets the villus height
      (V) and crypt depth (C) were increased, and the V:C ratio was decreased (p <
      0.01). The PCNA and TUNEL immunoreactivities were also tested. The number of
      mitotic mucosal cells (M) was increased, and that of mucosal cells with apoptotic
      nuclei (A) decreased in such a way that the A:M index diminished (p < 0.01). The
      A:M index also decreased at the level of some components of the gut-associated
      lymphatic tissue (GALT), thus indicating a positive effect on the gut barrier
      function. This trial showed that L: -glutamine supplementation influenced some
      morphofunctional characteristics of piglet ileal mucosa. These data corroborate
      the nutraceutical role of glutamine as a trophic agent for mucosal repair,
      improvement of barrier function and gut adaptation in the swine per se and as an
      animal model.

PMID- 16437312
TI  - [How important is the norovirus relationship to gastroenteritis ].

PMID- 16437313
TI  - Food-borne norovirus outbreaks: a nuisance or more than that?

PMID- 16437314
TI  - [Direct and indirect antithrombins in acute coronary syndromes].
AB  - Unfractionated heparin (UFH) as well as low-molecular-weight heparins (LMWH),
      especially enoxaparin, are recommended by the current international guidelines
      for routine used in the conservative treatment of patients with acute coronary
      syndromes (ACS). UFH is still the recommended antithrombin as soon as
      percutaneous coronary interventions (PCI) are performed, although the results of
      different trials clearly have demonstrated the benefit of enoxaparin also in
      interventional cardiology. Bleeding complications along PCI procedures can be
      minimized by avoiding crossover from enoxaparin to UFH or vice versa and by
      reducing the dosage of indirect antithrombins, particularly of enoxaparin, in
      patients with chronic renal dysfunction and/or the elderly. Especially for those
      patient groups, bivalirudin offers already today an effective alternative. There
      is increasing expectation concerning the use of bivalirudin in patients
      undergoing PCI procedures but firm data exist at present only for low- and medium
      risk patients with non ST-elevation ACS. Results of still ongoing trials (ACUITY,
      HORIZONS) will help to further confirm the role of bivalirudin in patients with
      high-risk acute coronary syndromes. For other direct antithrombins, e.g.,
      fondaparinux (a pentasaccharide) or melagatran, comparably few data are available
      at present. Whether these agents will make their way into clinical use, future
      will tell.

PMID- 16437315
TI  - Multiple inappropriate defibrillator discharges due to Twiddler's syndrome.

PMID- 16437316
TI  - An outbreak of Norovirus infection affecting an Austrian nursing home and a
      hospital.
AB  - On November 9, 2004, a resident in a nursing home experienced a severe episode of
      vomiting in the dining room, in the presence of most of the other residents and
      members of staff. Following that episode, 17 of the 23 (73.9%) other residents
      and 7 of the 18 (38.9%) staff members fell ill with diarrhea and/or vomiting in
      the period up to November 17. A second cluster of gastroenteritis occurred
      between November 11 and 28, 2004, in a nearby hospital to which eight cases among
      the nursing home residents had been referred. Ten of 46 (21.7%) other hospital
      patients and 18 of 60 (30%) members of the hospital staff suffered from vomiting
      or diarrhea. Epidemiological and laboratory investigations proved a causal
      relationship between the two institutional clusters of short-lived
      gastroenteritis related by time and place, and identified Norovirus genotype
      GGII.4 (Jamboree-like) as the causative pathogen. Control measures for Norovirus,
      based on epidemiological and clinical features of the outbreak, were effectively
      implemented in the nursing home without waiting for virological confirmation. At
      the hospital, specific measures were not implemented until after virological
      confirmation of the causative agent, by which time 16 cases had already occurred.
      In a suspected Norovirus outbreak it is of great importance -- especially within
      closed and semiclosed settings -- to implement control measures as soon as
      possible, even before laboratory confirmation of the agent.

PMID- 16437317
TI  - Pyogenic liver abscesses with Escherichia coli: etiology, clinical course,
      outcome, and prognostic factors.
AB  - BACKGROUND: To investigate the clinical characteristics, outcome, and prognostic
      factors related to mortality in patients with Escherichia coli liver abscess.
      METHODS: We retrospectively analyzed 72 patients aged 18 years and older who were
      diagnosed as having E. coli liver abscesses from July 1996 to June 2002 at two
      medical centers in Taiwan. RESULTS: The overall mortality rate was 26.4%. The
      majority of E. coli liver abscesses was solitary, involved the right lobe of the
      liver, and comprised polymicrobial infections. The cause of the liver abscess
      involved the biliary system in 48 patients (66.7%). The most common concomitant
      diseases were diabetes mellitus (30.6%) and underlying malignancy (30.6%).
      Metastatic infection was found in 4 patients (5.6%). Multivariate analysis
      revealed that underlying malignancy (p = 0.034), profound hypoalbuminemia (<2.5
      g/dl) (p = 0.008), and multiple abscesses (p = 0.004) were the most significantly
      prognostic factors for mortality. CONCLUSION: The predominant causes of E. coli
      liver abscess were biliary diseases. This report also highlights that E. coli
      liver abscess has a relatively high mortality rate, which is associated with
      underlying malignancy, multiple abscesses and profound hypoalbuminemia.

PMID- 16437318
TI  - Regular physical exercise normalizes elevated asymmetrical dimethylarginine
      concentrations in patients with type 1 diabetes mellitus.
AB  - INTRODUCTION: Levels of the endogenous nitric oxide synthase inhibitor
      asymmetrical dimethylarginine (ADMA) are elevated in patients with type 1
      diabetes mellitus (DM1) and may contribute to vascular complications. In this
      study we tested the hypothesis that elevated ADMA in patients with DM1 can be
      reduced by regular physical exercise. METHODS: Plasma samples for analysis of L
      arginine, ADMA, symmetrical dimethylarginine (SDMA) and metabolic parameters were
      obtained from 11 patients with DM1 who participated in a supervised aerobic
      exercise program for four months. Samples were collected before the training
      began, at two and four months after initiation, and eight months after cessation
      of regular training. Fifteen age- and sex-matched healthy persons who did not
      exercise regularly were examined once as controls and did not participate in the
      training program. RESULTS: The patients with DM1 had higher ADMA levels than the
      controls before the training program began (0.54 +/- 0.02 vs. 0.44 +/- 0.03
      micromol/l; P < 0.05). After two and four months of exercise, ADMA concentrations
      in the patients decreased to those seen in healthy persons (0.42 +/- 0.02 and
      0.43 +/- 0.03 micromol/l; P < 0.001 and P < 0.05 compared with ADMA levels before
      training began). Eight months after cessation of the exercise program, ADMA
      levels in the patients reverted to those observed before the start of training.
      The L-arginine-to-ADMA ratio increased slightly after two months; L-arginine,
      symmetrical dimethylarginine, blood lipids and HbA1c were not affected by the
      training program. CONCLUSIONS: Elevated ADMA levels in patients with DM1, who
      have a high risk for developing cardiovascular disease, can be lowered to those
      of healthy persons by regular physical exercise. This favorable effect on ADMA is
      not sustained when training is discontinued.

PMID- 16437319
TI  - Retrospective analysis of re-irradiation in malignant glioma: a single-center
      experience.
AB  - INTRODUCTION: Malignant gliomas are brain tumors deriving from the brain's glia
      cells. Primary treatment comprises resection, irradiation and chemotherapy, but
      these tumors almost always recur. In this situation, palliative chemotherapy is
      relatively well established, but a second local treatment is sometimes possible.
      We evaluated the safety and efficacy of re-irradiation in patients with recurrent
      malignant glioma. PATIENTS AND METHODS: Twenty-two patients were treated with a
      second irradiation for recurrent or progressive glioma. Patients either received
      hypo-fractionated stereotactic treatment or conventionally fractionated conformal
      therapy, depending on tumor size. Wherever possible, a second resection was
      performed. Time to progression (TTP) and survival were estimated using the Kaplan
      Meier product-limit method. RESULTS: Median age was 31 (8-77) years. Median TTP
      after onset of re-treatment was 4 (1-31) months. Median overall survival was 7 (1
      46) months, and overall survival from primary diagnosis was 49 (7-136) months.
      Significantly longer TTP (P = 0.008) and overall survival (P = 0.005) were
      observed in re-resected patients than in those without a second surgical
      intervention. CONCLUSION: Re-irradiation in malignant glioma is a feasible and
      safe treatment option, and the benefit appears to be especially large in re
      resected patients. To make a final conclusion possible, larger prospective trials
      are warranted.

PMID- 16437320
TI  - Prediction of success in the first-year exam in the study of medicine--a
      prospective survey.
AB  - OBJECTIVE: To identify predictors of students' success in the first-year exam in
      a new curriculum in the study of medicine in Vienna. DESIGN: We tested 11 topics
      (including socio-demographic variables, family background, school performance,
      economic situation, living conditions, social integration and health, learning
      capacity, study motivation and ability to cope with stress) for their relevance
      in terms of study success in a prospective study of an unselected student sample.
      Data were collected from questionnaires filled in by 674 first-year students
      (50.8% of the total number of 1327 new students) who enrolled in the academic
      year 2002/03. MAIN OUTCOME: Comparison of students who passed the first-year exam
      with students who failed identified four predictors: male sex, German mother
      tongue, performance in secondary school and learning capacity. CONCLUSIONS: The
      new curriculum exerted subliminal selectivity; the predictive powers of school
      marks and subjective learning capacity were confirmed; the influence of a
      student's sex should be investigated further; the influence of mother tongue
      requires modification of pre-study courses for foreign students.

PMID- 16437321
TI  - Tandem high-dose chemotherapy supported by autologous peripheral blood stem-cell
      transplantation and radiotherapy for recurrent malignant fibrous histiocytoma.
AB  - Malignant fibrous histiocytoma (MFH) is a soft-tissue sarcoma created from
      fibroblast cells and characterized by a high rate of metastasis or recurrence
      with poor prognosis. We report a case of initially well differentiated (G1) MFH
      of the trunk in a 33-year-old woman. Two years after primary diagnosis,
      metastases were found in the lung, trunk, gluteus region, upper extremities and
      brain. Histopathological findings indicated a stromal tumor consisting of spindle
      cells, and immunohistochemical examination of resected specimens established the
      definite diagnosis of poorly differentiated MFH (G3). Initial surgery of several
      solid tumors on the trunk, lung and extremities was performed. There was a high
      local recurrence and metastasis rate, and the patient was treated with
      radiotherapy and conventional chemotherapy followed by tandem high-dose
      chemotherapy and peripheral blood stem-cell transplantation. She is currently
      well seven years after the transplant, with no signs of metastasis and
      recurrence. We review the clinical picture of the tumor in this patient and
      discuss its diagnosis, pathogenesis and treatment.

PMID- 16437322
TI  - A colloid cyst of the third ventricle -- the cause of episodic headache and
      sudden unexpected death in an adolescent girl.
AB  - An 18-year-old girl was found dead in her bed. The autopsy revealed a colloid
      cyst of the third ventricle. The cyst obstructed the flow of cerebrospinal fluid,
      leading to prominent internal hydrocephalus with consecutive brain edema and
      compression of the caudal medulla at the foramen magnum. The girl's only previous
      complaints were episodic headaches for the previous 2-3 years. Computed
      tomography and magnetic resonance imaging were not performed prior to her death.
      This case report highlights the importance of early diagnosis of colloid cyst of
      the third ventricle and the need to perform computed tomography and magnetic
      resonance imaging in patients with episodic headaches even when they show no
      neurologic deficit. Although it is a very rare disorder, it should be included in
      the differential diagnosis of headaches in children and young adults, and also in
      the differential diagnosis of conditions causing increased intracranial pressure,
      in view of the life-saving management required to prevent a fatal outcome.

PMID- 16437325
TI  - [How can the approach and the clinical results of peritoneal dialysis continue to
      be better in the future?].

PMID- 16437326
TI  - [Peritoneal dialysis indication--importance of psychosocial aspects of the
      indications of the situation].
AB  - Peritoneal dialysis treatment is as efficient as hemodialysis if properly
      administered; therefore, psychological aspects of peritoneal dialysis must be
      taken into account if this is to be the best treatment for patients suffering
      from terminal renal disease. This paper presents these aspects from the view of
      logotherapy and existential analysis. The description of the change in viewing
      patients from a medical aspect is followed by an outline of basic logotherapy and
      existential analysis. The consequences to patients and their current problems are
      described, together with theoretical basics and practical guidelines for
      communication with patients.

PMID- 16437327
TI  - [Peritoneal dialysis in children: an acceptable solution for patients but a
      challenge for their families].
AB  - The aim of this investigation was to gain a retrospective impression of the mood
      of children undergoing peritoneal dialysis and the mood of their families during
      the course of their children's disease. The study was carried out at the
      department of pediatric nephrology (Medical University of Vienna) using
      structured questionnaires. Interestingly, both the families undergoing treatment
      and families who had completed treatment considered themselves equally, or even
      more, happy, harmonic and open than families with healthy children.
      Retrospectively, intimate relationships experienced by the majority of families
      were exceptionally close and positive. These findings do not support the
      subjective evaluation of staff and are contrary to the objective measurability of
      financial and emotional investment, as well as investment of time, by affected
      families.

PMID- 16437328
TI  - [Withdrawal of dialysis--decision-making criterion].
AB  - Improvement in prolongation and quality of life has been made possible by medical
      progress, but life for the patient can become ever more dependent on artificial
      support and death may be prolonged in unwanted ways. The choice between
      prolongation of life, quality of life and the abatement of suffering is of great
      importance in decisions on the continuation or cessation of dialysis and is
      naturally a process of weighing different positions. This process requires not
      only medical decision-making but also a structure for the organization of
      communication between all involved parties. Only thus is it possible to reach a
      satisfactory resolution to such a situation, a resolution that shows medical
      responsibility on the part of the physician and one that can be borne by all
      those involved.

PMID- 16437329
TI  - [Peritoneal dialysis in patients with polycystic kidney disease].
AB  - In Austria, patients with end-stage renal disease caused by polycystic kidney
      disease are less frequently treated with peritoneal dialysis (PD) than patients
      with noncystic renal diseases (6% versus 8%). In contrast, the United States
      renal data system reports that more than one fifth of patients with polycystic
      kidney disease choose PD as their initial form of renal replacement therapy. The
      reasons for this difference are unknown. Extrarenal manifestations of the
      disease, such as diverticulosis, development of hernias or vascular aneurysms,
      may theoretically promote the occurrence of complications typically related to
      PD. However, studies undertaken to clarify these questions did not find any
      difference in the rates of peritonitis caused by diverticulosis or Gram-negative
      bacteria, and no differences were seen with respect to vascular complications.
      Nevertheless, in comparison with the general population, patients with polycystic
      kidney disease are more likely to develop hernias, and the incidence of
      herniation may be further increased by PD. In conclusion, patients with
      polycystic kidney disease who also have abdominal complaints such as meteorism
      and discomfort, or lumbago resulting from the markedly enlarged kidneys, should
      not be actively advised to have PD treatment. The same is true for patients with
      recurrent hernias. However, the technical survival, quality of dialysis, duration
      of therapy and rates of complications in PD are comparable in patients with
      cystic or noncystic kidney disease, and therefore all patients with polycystic
      kidney disease who do not have abdominal complaints or history of recurrent
      hernias should be informed that PD is an adequate form of renal replacement
      therapy, equally effective as hemodialysis.

PMID- 16437330
TI  - [Peritoneal dialysis in patients with diabetic nephropathy].
AB  - Since the introduction of peritoneal dialysis (PD) into clinical nephrology at
      the end of the 1970s, many improvements have led to acceptance of this method as
      renal replacement therapy equivalent to hemodialysis. It is unclear whether the
      diabetic patient is the ideal candidate for PD and if this procedure should be
      the preferred method of treatment of renal failure in these patients, especially
      when kidney transplantation cannot be performed. PD may provide several
      advantages for diabetic patients with end-stage renal failure; for example,
      better hemodynamic stability is achieved during peritoneal ultrafiltration and
      vascular access surgery becomes unnecessary. On the other hand, the continuous
      glucose absorption may lead to increased insulin requirements, obesity and
      hyperlipidemia. Furthermore, peritoneal protein loss may aggravate malnutrition,
      which is frequently present in these patients. However, for a differentiated
      assessment of outcome in PD, the individual history (diabetes type 1 or type 2)
      and accompanying comorbidity of diabetic patients have to be considered. Nowadays
      nephrologists have to be aware of the concept of individualized therapy, which is
      integrated into an overall plan and takes into account the different conditions
      of diabetic patients and their treatment options. By improving removal of sodium
      and water, as well as improving quality of metabolic control, new dialysis
      solutions (icodextrin, neutral-pH solutions) and automated PD could have a
      positive impact on outcome in diabetic patients. In contrast, from retrospective
      studies on PD there is evidence of higher long-term mortality rates in elderly
      women with diabetes and in patients with cardiac insufficiency than in those on
      hemodialysis. Further research is necessary in order to optimize individualized
      therapy for diabetic patients with end-stage renal disease in the future.

PMID- 16437331
TI  - [Peritoneal dialysis in patients with chronic kidney-graft failure].
AB  - Patients with chronic kidney-graft failure who are starting peritoneal dialysis
      (PD) treatment need special consideration. The question of whether mortality is
      higher in these patients than in those who have not received a transplant is
      controversial. However, some studies suggest that differences in mortality
      between these groups are mainly explained by variations in age, duration of
      dialysis and comorbidity. One study showed similar survival between patients with
      chronic graft failure treated with hemodialysis (HD) and those on PD, but there
      is some evidence that residual renal function in PD patients with chronic graft
      failure declines faster than in PD-patients without transplants. Until now there
      have been no data on whether PD has a positive influence on the course of
      residual renal clearances compared with the influence of HD. The fact that PD
      patients with transplants show significantly higher peritoneal transport rates
      than patients without transplants may have an influence on technique survival. In
      patients with chronic graft failure, the type and dose of immunosuppressive
      therapy, as well as its influence on the incidence of acute rejections, residual
      renal function and infection rates, are also controversial. Immunosuppressive
      therapy may preserve residual graft function, but these patients have a higher
      risk of Gram-negative peritonitis, a shorter interval between start of dialysis
      and first episode of peritonitis, and a higher risk of catheter infections with
      Staphylococcus aureus than PD patients without transplants. In conclusion, PD is
      an acceptable treatment option for patients with chronic kidney-graft failure
      provided that the above clinical aspects are considered (e.g., intensified
      monitoring of infections and residual renal function).

PMID- 16437332
TI  - [Peritoneal dialysis in patients with high body-mass index].
AB  - Most physicians do not consider peritoneal dialysis (PD) to be the treatment of
      choice in obese patients with end-stage renal failure. In some but not all
      studies the incidence of infectious complications (catheter-associated infections
      and peritonitis) is higher than in patients with normal body mass index (BMI).
      Although mathematical models show that even continuous ambulatory PD with a daily
      dialysate treatment volume of 12 litres does not provide sufficient clearances in
      patients weighing 80 kg, adequate dialysis has been achieved in clinical studies
      in patients with BMI up to 46 kg/m2. Residual renal function is a very important
      factor for survival in patients undergoing PD and might be influenced by body
      weight; however, data are controversial, showing either a negative influence of
      high BMI on renal clearance or no association. The incidence of peritoneal leaks
      in PD is higher in obese patients than in other patients, because of the raised
      intra-abdominal pressure. In contrast, hernias do not occur more frequently in
      overweight PD patients and the risk of hernias seems to be greater in patients
      with lower BMI. It is well known that mortality rates of overweight patients on
      hemodialysis are lower than in those with normal body weight, but data on the
      influence of BMI on survival in PD patients are more controversial. In
      conclusion, there is no evidence that PD is absolutely contraindicated in
      patients with high BMI, especially if patients have a strong preference for this
      type of treatment.

PMID- 16437333
TI  - [Peritoneal dialysis and cardiopulmonary comorbidity].
AB  - The number of patients suffering from end-stage renal disease (ESRD) throughout
      the world continues to increase. The unacceptably high mortality in this
      population has led to current efforts to optimize dialysis treatment and has
      focused attention on comorbidities and their interaction with dialysis treatment.
      Cardiovascular morbidity is the most important cause of death in patients with
      ESRD. The advantages of hemodynamic stability and volume regulation offered by
      peritoneal dialysis (PD), compared with hemodialysis (HD), have made PD
      preferable for patients with cardiovascular comorbidity. However, recent studies
      on PD have shown a higher mortality in patients with coronary artery disease or
      congestive heart failure than in similar patients receiving HD. Nevertheless, the
      validity of the studies is limited by their retrospective study design and,
      furthermore, at the time of data collection, new dialysis solutions were not
      available and the percentage of patients on automated PD was low. Little is known
      about the frequency of chronic obstructive pulmonary disease (COPD) in the ESRD
      population, but COPD data on the general population without kidney disease
      suggest that significant underestimation of both prevalence and mortality of this
      disease can be supposed in the ESRD population. Data currently available do not
      suggest that PD is contraindicated in patients with cardiac diseases. However,
      consequent diagnostic and therapeutic interventions of cardiac comorbidities and
      corresponding risk factors are required. Patients suffering from mild COPD should
      not be generally excluded from PD as renal replacement therapy, although
      individually tailored modifications of dialysate volume and frequency of
      exchanges are often required.

PMID- 16437334
TI  - [Peritoneal dialysis in patients with liver cirrhosis and/or ascites].
AB  - In older textbooks the use of peritoneal dialysis (PD) in patients with liver
      cirrhosis and/or ascites was contraindicated. Only a small number of papers have
      focused on this problem and they mainly consist of case reports and retrospective
      studies of small numbers of patients. In addition, most nephrologists' experience
      of performing PD in patients with liver diseases is rather limited. Nevertheless,
      for these patients PD offers a wide range of advantages, such as a simplified
      ascites management, since repeated abdominal punctures become unnecessary.
      Furthermore, because of continuous peritoneal ultrafiltration, hemodynamic
      tolerance during PD is significantly better than in hemodialysis and results in a
      markedly lower frequency of hypotensive episodes. The risk of nosocomial
      infection with hepatitis B or C viruses can also be reduced by treating these
      patients with home PD. Although some authors suggest that PD patients with liver
      cirrhosis have an especially increased risk of Gram-negative peritonitis,
      currently available data show controversial results. There is also little
      information in the literature on the impact of increased peritoneal protein loss
      on malnutrition and outcome of these patients. Nevertheless, recent studies have
      shown that protein loss into the peritoneal cavity in PD patients with liver
      cirrhosis is high only initially, stabilizing at a lower level in the further
      course of treatment. In conclusion, in patients with end-stage renal disease
      suffering from liver cirrhosis and/or ascites, PD can be considered as a good or
      adequate treatment option.

PMID- 16437335
TI  - [Comparison of clinical outcomes in peritoneal dialysis and hemodialysis].
AB  - In addition to kidney transplantation, peritoneal dialysis (PD) and hemodialysis
      represent two options for renal replacement therapy in patients with end-stage
      renal disease (ESRD). Given that most patients are suitable for both types of
      dialysis and that many of them require lifelong therapy, differences in clinical
      outcome between these treatments are of major interest. Differences between the
      two dialysis treatments have been described in single clinical aspects (e.g.,
      hyperkalemia, volume status, blood pressure control, cardiac complications), the
      relevance of which are reflected by mortality rates. Data available so far
      indicate that overall outcome of patients with ESRD is comparable in the two
      types of dialysis. However, there are significant differences in subgroups of
      patients, such as those with diabetes or coronary heart disease. In order to
      achieve the best possible survival and quality of life in ESRD, the optimal
      sequence of dialysis treatments during the course of renal replacement therapy,
      rather than a single type of treatment, has to be considered. The "integrated
      care concept" takes into account this sequence of dialysis treatments, suggesting
      that patients should start on PD but be transferred to hemodialysis as soon as PD
      is no longer adequate. This concept allows longer preservation of residual renal
      function, better early survival on dialysis and better short-term results of
      graft survival after kidney transplantation. Thus, if medically suitable, PD
      should be the first treatment option in patients with ESRD who need renal
      replacement therapy.

PMID- 16437336
TI  - [Anemia and its treatment in peritoneal dialysis patients].
AB  - The need for erythropoietin (rhuEPO) or darbepoetin-alpha and iron is lower in
      patients undergoing peritoneal dialysis (PD) than in patients treated with
      hemodialysis (HD) because blood losses are reduced, residual renal function and
      elimination of inhibitors of erythropoiesis are improved and inflammation is less
      than in HD treatment. In addition, comorbidities of PD patients are probably
      lower than those of HD patients, and this factor may also contribute to anemia
      being less in PD patients than in those on HD. Furthermore, the frequency of
      blood transfusions is lower in PD patients, with or without rhuEPO treatment.
      However, in PD patients also, anemia is associated with hospitalization rate and
      mortality. Anemia can be corrected by subcutaneous injections of rhuEPO-beta (1-3
      times per week) or darbepoetin-alpha (once a week or twice a month). Adjuvant
      treatment of anemia includes correction of iron deficiency by oral or intravenous
      iron, androgen substitution in elderly male PD patients and adequate calcitriol
      supplementation. Factors that may negatively influence anemia in PD patients are
      inflammation, infection, antihypertensive therapy with ACE inhibitors or
      angiotensin II blockers and neutralizing antibodies against rhuEPO or darbepoetin
      alpha.

PMID- 16437337
TI  - [Prophylaxis and management of catheter-associated infections in peritoneal
      dialysis patients: recent studies and guidelines].
AB  - Prophylaxis and treatment of catheter-related infections in patients undergoing
      peritoneal dialysis (PD) are the key to success of this type of renal replacement
      therapy. Prophylactic antibiotic therapy before catheter implantation
      significantly reduces the risk of peritonitis in the first month after operation.
      However, this strategy does not influence the risk of infections of the exit site
      and catheter tunnel. Although there are no studies showing any benefit in the use
      of povidon-iodine or sodium hypochlorite for care of exit sites in long-term PD
      patients, the use of a local disinfectant is recommended in recent guidelines.
      Another prophylactic approach is the use of local antibiotics, either
      intranasally or by application to the exit site. The use of mupirocin
      significantly reduces the rate of exit-site and tunnel infections and also the
      number of Staphylococcus aureus carriers. Gentamycin cream applied to the exit
      site is as effective as mupirocin in preventing S. aureus infections and in
      addition covers Pseudomonas aeruginosa. Both these local antibiotic therapies,
      however, carry the risk of selection of resistant bacterial strains. Guidelines
      mostly recommend the use of local antibiotics at least in S. aureus carriers.
      According to available data, oral antibiotic prophylaxis in long-term PD patients
      is not recommended, since a positive effect is unproven and systemic side effects
      have been reported in some studies. Family members and healthcare workers may be
      a source of S. aureus colonization in PD patients; however, there are no
      international protocols suggesting screening or treatment of these persons. There
      is no evidence favoring any dressing protocol (or a dressing change at all).
      Furthermore, because of lack of data, the question of whether face masks should
      be used during dressing changes or dialysate exchanges cannot yet be answered.
      There are no studies showing that it is safe for PD patients to go swimming or to
      a sauna. Only a few studies have focused on diagnosis and classification of exit
      site infections and therefore no international standards exist. In cases of exit
      site infection, ultrasonography of the catheter tunnel is a useful tool in the
      diagnosis of accompanying tunnel involvement and is also helpful in estimating
      the prognosis of these infections, depending on response to antibiotic therapy.
      Catheter-related infections should be treated with antibiotics for at least two
      weeks. With the exception of infection with methicillin-resistant S. aureus, the
      oral route is as effective as intraperitoneal administration. Currently there is
      no evidence of the ideal time-point for catheter removal after renal
      transplantation.

PMID- 16437338
TI  - [Adequate peritoneal dialysis--new guidelines?].
AB  - The role of peritoneal dialysis (PD) in renal replacement therapy has been well
      established. However, there is persisting controversy about the amount of
      dialysis that is required for optimal outcome. On the basis of the results of
      clinical studies of patients treated with continuous ambulatory peritoneal
      dialysis (CAPD), NFK-DOQI guidelines recommended achieving a Kt/Vurea of >or=2.0
      per week and a total creatinine clearance of >or=50 l/week/1.73 m2 (low/low
      average transporters) to 60 l/week/1.73 m2 (high/high-average transporters). In
      automated PD, the targets are slightly higher (>or=2.1 per week and >or=63
      l/week/1.73 m2, respectively). In the DOQI guidelines, renal and peritoneal
      clearances are assumed to be equivalent; therefore it has been supposed that
      increasing the dialysis dose could compensate for the loss of residual renal
      function (RRF). Several retrospective studies analyzed the effect of peritoneal
      and renal clearances separately and did not find a correlation between peritoneal
      small-solute clearance and mortality. However, RRF was an important factor
      influencing mortality of PD patients. The Adequacy of Peritoneal Dialysis in
      Mexico (ADEMEX) study is a randomized, prospective study that was designed to
      investigate the effect of PD dose on clinical outcome in CAPD patients. This
      study also showed that RRF, but not peritoneal clearance, predicted clinical
      outcome. An increase of PD dose (from 1.8 to 2.27 Kt/V per week) did not improve
      patient survival or technique survival. On the basis of the result of ADEMEX and
      some other clinical studies, a combined renal and peritoneal Kt/V of 1.8/week
      appears to be adequate in most clinically stable PD patients without signs of
      malnutrition. Nevertheless, there are no patient-survival data on the influence
      of peritoneal small-solute clearances, which are markedly higher than those
      recommended in the DOQI guidelines. On the other hand, important determinants of
      adequate PD include not only small-solute clearances but also middle-molecule
      clearances, preservation of RRF, careful attention to volume status, treatment of
      cardiovascular risk factors, and treatment of malnutrition and other
      comorbidities.

PMID- 16437339
TI  - [Influence of new dialysis solutions on clinical results in patients treated with
      peritoneal dialysis].
AB  - Long-term peritoneal dialysis is associated with changes in the peritoneal
      membrane. Conventional dialysate solutions are bioincompatible because of their
      low pH, high glucose content, hyperosmolality and increased concentration of
      glucose degradation products. The development of double-compartment systems has
      made it possible to separate glucose from the buffer during heat sterilization,
      resulting in a higher or even physiologic pH of the solution with reduced
      concentration of glucose degradation products. These new solutions are less toxic
      for several cell groups and are better than conventional solutions in preserving
      membrane function, as demonstrated by experiments in rats. Glucose degradation
      products promote formation of advanced glycation end-products, and plasma levels
      of these are markedly reduced when double-compartment systems are used. Clinical
      studies with these more physiologic dialysis solutions have demonstrated better
      correction of acidosis, less inflow pain, significantly elevated CA-125 dialysate
      levels and lower concentrations of markers for inflammation and fibrosis in the
      effluent. In a retrospective study, a lower rate of mortality was observed in
      patients who were treated using a double-compartment system than in those treated
      with standard dialysis solution. Amino acids (in the low-molecular-weight range)
      and icodextrin (in the high-molecular-weight range) are newer osmotic agents that
      have been developed as alternatives to glucose. Several clinical studies have
      shown that amino-acid solution improves various nutritional parameters in
      patients with malnutrition and is more biocompatible than standard glucose
      solution. Icodextrin is an iso-osmolar dialysis solution. Ultrafiltration takes
      place via colloid osmotic pressure and is sufficient in all types of peritoneal
      transport. Clinical studies using icodextrin have shown better fluid control,
      especially in high transporters, reduced carbohydrate load and fewer patients
      with ultrafiltration failure compared with those treated with conventional
      dialysis solutions. However, allergic skin reactions have been observed in up to
      10% of patients treated with icodextrin. Icodextrin may induce a fall of sodium
      plasma levels. Because of cross-reaction with elevated plasma levels of maltose,
      serum amylase is determined falsely low and glucose (using the glucose
      dehydrogenase method) is measured falsely high, but high plasma levels of maltose
      do not affect measurement of lipase or measurement of glucose using the glucose
      oxidase method. New dialysate solutions will have a positive influence on both
      survival and technical drop-out rates in patients receiving peritoneal dialysis
      treatment.

PMID- 16437340
TI  - [Automated peritoneal dialysis--actual clinical aspects].
AB  - Automated peritoneal dialysis (APD) is an important treatment option in PD
      patients with high peritoneal transport rates, in patients with inadequate small
      solute clearances during continuous ambulatory peritoneal dialysis (CAPD)
      treatment, and in patients with complications associated with high
      intraperitoneal pressure. Because APD offers better flexibility during the
      daytime, patients often have a better quality of life and are able to go to work
      or school. However, APD is more expensive and technically more complex than CAPD
      and there are controversial results on the course of residual renal function and
      the risk of peritonitis in the two types of treatment. The increased elimination
      of antibiotic drugs during cycler therapy has to be considered in patients with
      peritonitis, especially in those using high treatment volumes. When used during
      the daytime dwell, polyglucose solution has been shown to improve ultrafiltration
      and reduce the extracellular fluid volume in PD patients. In comparison with
      conventional dialysis solutions, treatment with pH-neutral solutions allows
      better correction of metabolic acidosis and is associated with an increase of CA
      125 dialysate concentrations and a reduction of infusion pain. Tidal PD has its
      place in patients with mechanical outflow problems; however, compared with
      conventional APD, there is no improvement of clearances when the dialysate flow
      is kept constant. Continuous-flow PD using a double-lumen catheter is more
      effective but also more expensive than conventional APD. Most studies report a
      similar or even better patient survival with APD than with CAPD; however, a
      selection bias cannot be excluded from these mainly retrospective studies. In
      summary, APD is an established method of PD treatment that provides several
      advantages to patients and contributes to decreased technical drop-out rates.

PMID- 16437341
TI  - Building up original evidence.

PMID- 16437342
TI  - Total en bloc spondylectomy for spinal tumors: improvement of the technique and
      its associated basic background.

PMID- 16437343
TI  - Incidence and prognostic factors of Japanese breast cancer patients with bone
      metastasis.
AB  - BACKGROUND: Few previous studies have analyzed the incidence of bone metastases
      in a defined population of Japanese breast cancer patients and their prognosis
      after chemotherapy. METHODS: This is a retrospective cohort study. We
      investigated 695 patients who underwent surgery for breast cancer. The strategy
      of adjuvant therapy was as follows. Patients with both estrogen receptors (ERs)
      and progesterone receptors (PgRs) had endocrine therapy as initial adjuvant
      therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When
      metastasis to other organs, including bone, was identified, patients received
      chemotherapy. The survival rates after surgery and after the onset of bone
      metastasis, as well as the incidence of bone metastasis, were calculated. We also
      evaluated the prognostic and predictive factors. RESULTS: Bone metastases
      developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them
      developed spinal metastases. The 5-year survival rate after bone metastases was
      26.1%. Prognostic factors for bone metastases were visceral metastases and PgR
      status. Cord compression was observed in 17 of the 148 patients, with the
      thoracic spine being the most common. The 1-year survival rate for patients with
      bone metastases who received chemotherapy was 66.3%, whereas that of patients
      with paralysis after spinal metastases was 17.6%. Within 6 months of the
      development of spinal cord compression, 70.6% of the patients died. CONCLUSIONS:
      We reported the incidence and prognostic factors for a defined population of
      Japanese breast cancer patients with bone and spinal metastases. Our results
      suggest that the expected survival time for patients with paralysis who received
      adequate endocrine therapy or chemotherapy is generally poor. However, to detect
      a predictive factor of long survival after paralysis and establish the
      indications for surgery, a comparative study among large groups of patients with
      paralysis and with different backgrounds is necessary.

PMID- 16437344
TI  - Randomized prospective study on prophylactic antibiotics in clean orthopedic
      surgery in one ward for 1 year.
AB  - BACKGROUND: At present in Japan, there are neither reports on antibiotic
      prophylaxis regardless of underlying diseases nor precise guidelines on
      prophylactic antibiotics in orthopedic surgery. Therefore, the preventive effect
      of antimicrobial agents on surgical site infection (SSI) after clean orthopedic
      surgery was studied to control the prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) in our ward and to reduce SSI caused by MRSA.
      METHODS: Regardless of the type of operation or underlying disease, a regimen of
      prophylaxis that is of shorter duration than before was conducted in 419 patients
      admitted to our orthopedic ward (one ward) and who underwent clean orthopedic
      surgery between 2001 and 2002. RESULTS: The annual usage of beta-lactam
      antibiotics in the ward decreased by 960.9 g, the isolation rate of MRSA in the
      ward decreased to 50% (the lowest isolation rate in the past 4 years), and SSIs
      caused by MRSA were found in 3 of 419 (0.71%) patients in one year compared with
      6 of 470 (1.28%) during the previous year. Comparison of two antibiotics revealed
      that SSI caused by MRSA did not occur in any of the 187 patients receiving
      sulbactam/ampicillin as prophylaxis but did occur in 1.29% (3/232) patients
      receiving cefazolin. Concerning all SSIs caused by any organisms, they occurred
      in 0.53% of patients receiving sulbactam/ampicillin and in 2.16% of patients
      receiving cefazolin. The difference in the SSI rates between the two groups was
      not statistically significant. CONCLUSIONS: Although there is statistically no
      significant difference in the incidence of SSI caused by MRSA, we were able to
      decrease the isolation rates of MRSA and prevent MRSA from spreading owing to the
      reduced antibiotic usage in this study. Sulbactam/ampicillin can be recommended,
      as well as cefazolin, for antibiotic prophylaxis in clean orthopedic surgery.

PMID- 16437345
TI  - Pseudoarthrosis of vertebral fracture: radiographic and characteristic clinical
      features and natural history.
AB  - BACKGROUND: We examined mobility based on radiographic appearance, clinical
      appearance, and the natural course of osteoporotic vertebral pseudoarthrosis
      (VPA) in a prospective study in 34 consecutive cases of VPA in 27 patients with
      osteoporosis. METHODS: Conventional lateral, lateral flexion, and extension
      stress radiography (XP) and supine cross-table lateral XP were performed.
      Anterior vertebral body height and vertebral kyphotic angle were measured to
      assess vertebral mobility. If vertebral cleft or vertebral instability, which
      means a difference in vertebral body height between conventional and supine cross
      table lateral XP, was present, VPA was diagnosed. Back pain was classified into
      five grades. RESULTS: The average anterior vertebral height was 9.9 +/- 5.6 mm on
      conventional lateral XP; it increased to 11.4 +/- 6.5 mm on extension stress XP
      (not significant) and 18.3 +/- 5.7 mm on cross-table lateral XP (significant).
      The vertebral kyphotic angle was 24.1 degrees +/- 9.7 degrees on conventional
      lateral XP; it decreased to 21.6 degrees +/- 9.8 degrees on extension stress XP
      (not significant) and 11.8 degrees +/- 8.5 degrees on cross-table lateral XP
      (significant). Intravertebral clefts were detected by conventional lateral XP,
      extension stress XP, and supine cross-table XP in 3 of 34 (8.8%), 7 of 21
      (33.3%), and 28 of 34 (82.4%) vertebral compression fractures (VCFs),
      respectively. Surgical treatment was performed in seven patients (two because of
      severe pain and five because of neurological deficits) and in one patient who
      died. Except in these eight patients, back pain decreased by at least one grade
      with time in 18 of 19 patients (95%) in whom the clinical course was analyzed.
      Radiographic follow-up using supine cross-table XP was performed in 15 of 19
      patients. Although 11 of these 15 patients (73%) showed vertebral instability on
      supine cross-table lateral XP, 10 of 11 patients (91%) did not complain of
      intolerable back pain during daily activity at the final follow-up. CONCLUSIONS:
      VPA is often detected on supine cross-table lateral XP but not usually on
      extension stress XP. Despite the presence of vertebral instability, many patients
      did not complain of intolerable back pain during their daily activity. Surgical
      treatment to alleviate back pain should be performed for painful VPA after
      conservative treatment for about 4 months.

PMID- 16437346
TI  - Single center experience of treatment of Ewing's family of tumors in Japan.
AB  - BACKGROUND: Japanese patients with the Ewing's family of tumors (EFTs) reportedly
      have a worse prognosis than their European Caucasian counterparts. However,
      details of the prognosis of Japanese EFT patients have not been clearly defined
      because of the lack of representative clinical studies of the results of
      contemporary, multidisciplinary treatments. METHODS: The present study analyzed
      the outcome of 19 consecutive patients with EFTs who were treated with a
      multidisciplinary approach at a single institution. Combination chemotherapy
      consisting of vincristine, actinomycin D, Adriamycin (doxorubicin), and
      ifosfamide was administered as induction chemotherapy. Local therapy was
      administered individually, considering various factors, with the ultimate aim of
      complete surgical resection. Nine patients who satisfied the inclusion criteria
      received high-dose chemotherapy with peripheral blood stem cell rescue as a
      consolidation treatment. RESULTS: The 3-year overall and event-free survival
      rates were 62% and 51%, respectively, which were comparable to results from
      Western countries, although the number of subjects was too small to allow
      definitive conclusions to be drawn. CONCLUSIONS: There is a clear need to
      investigate the results of treatment of Japanese EFT patients in a
      multiinstitutional, prospective clinical study.

PMID- 16437347
TI  - Muscle activity during a dash shown by 18F-fluorodeoxyglucose positron emission
      tomography.
AB  - BACKGROUND: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has
      been used to examine muscle activity during running. The dash is a basic activity
      in various kinds of sports but differs from running in terms of intensity and
      severity. The purpose of this study was to evaluate muscle activity during
      running at full speed using FDG PET. METHODS: Six healthy men were investigated
      during a dash for 10 min after intravenous injection of FDG (37 MBq). Another six
      healthy men were studied as controls. PET images were obtained 45 min after the
      FDG injection. Regions of interest were drawn on the anterior and posterior
      thighs and the anterior and posterior legs. The standardized uptake value (SUV)
      was calculated to examine the FDG uptake of muscle tissue per unit volume
      according to an equation. RESULTS: In the control group, the mean SUVs of the
      anterior thigh, posterior thigh, anterior leg, and posterior leg were 0.49 +/-
      0.04, 0.44 +/- 0.02, 0.46 +/- 0.05, and 0.44 +/- 0.07, respectively. In the dash
      group, the mean SUVs of the anterior thigh, posterior thigh, anterior leg, and
      posterior leg were 0.74 +/- 0.20, 0.79 +/- 0.08, 0.61 +/- 0.07, and 0.60 +/-
      0.08, respectively. FDG accumulation of every one of the four compartments in the
      dash group was significantly higher than that in the control. FDG accumulation of
      the posterior thigh was significantly higher than that of the anterior and the
      posterior leg in the dash group (P < 0.02). CONCLUSION: Based on the results of
      our investigation, posterior thigh muscles were especially active during a dash.

PMID- 16437348
TI  - Antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus
      epidermidis biofilms isolated from infected total hip arthroplasty cases.
AB  - BACKGROUND: It is difficult to treat implant-related infections because bacteria
      form biofilms on implants. Biofilms protect the organisms from the host's immune
      system and prevent penetration of antimicrobial agents. We investigated the
      susceptibility of six strains isolated from infected total hip arthroplasty (THA)
      cases to six antimicrobial agents. METHODS: Six Staphylococcus aureus and S.
      epidermidis strains isolated from infected THA cases and S. aureus ACTT 25923,
      positive strains of biofilms, were used in this study. Biofilms were developed on
      96-well titer plates. After 7 days the nutrient solution was aspirated, and wells
      were rinsed three times with sterile water. A series of doubling dilutions of
      each antimicrobial agent (16, 32, 64, 128, 256, 512, and 1024 microg/ml) in
      trypticase soy broth were added to the wells. The plates were incubated at 37
      degrees C. After 24 h, the contents were aspirated and wells were rinsed three
      times with sterile water. The surfaces of wells were vigorously scraped with a
      sterile swab and applied to sheep blood agar plates at 37 degrees C in an aerobic
      chamber for 24 h. The minimum bactericidal concentrations (MBCs) were determined
      as the lowest concentration of antibiotic resulting in 100% reduction of viable
      cells compared to the antibiotic-free control. Biofilms were produced on
      stainless steel washers, and the time-course changes were observed by scanning
      electron microscopy (SEM). RESULTS: Planktonic bacteria were sensitive to the
      antimicrobial agents, but biofilm bacteria were markedly resistant. SEM revealed
      that biofilms grew larger with time. CONCLUSIONS: The MBCs of antimicrobial
      agents for biofilms bacteria were higher than those of planktonic bacteria.
      Therefore, it is suggested that implant-related infection is difficult to treat
      with antimicrobial agents alone.

PMID- 16437349
TI  - Expression of a novel alternatively spliced UCP-2 transcript in osteogenic
      sarcoma.
AB  - BACKGROUND: Development of chemoresistance is common in patients with osteogenic
      sarcoma (OGS); however, the underlying mechanism is largely unknown. Many
      anticancer drugs exert their therapeutic action by generating reactive oxygen
      radicals, which might be countered by the cancer cell through induction of
      uncoupling protein 2 (UCP-2). UCP-2 has been shown to be able to protect tumor
      cells from the cytotoxic actions of chemotherapeutic drugs. Because OGS is seldom
      completely cured by current chemotherapy regimens, we hypothesized that increased
      expression of UCP-2 underlies this phenomenon. The primary initial interest of
      our research was to evaluate the level of UCP-2 mRNA in OGS. METHODS: The level
      of UCP-2 mRNA was determined by reverse transcriptase polymerase chain reaction
      (RT-PCR) comparing expression in normal-bone-derived specimens and OGS-derived
      specimens. Semiquantification of mRNA expression was achieved by radioactive RT
      PCR. Nucleotide sequencing was performed using automated instruments. RESULTS:
      Interestingly, we failed to observe induction of UCP-2 mRNA in OGS tumor
      specimens and OGS-derived primary cell lines compared to the expression level in
      normal bone. However, we found expression of a hitherto unknown UCP-2 transcript
      in eight of eight OGS-derived and one EWS-derived cell lines and in nine of ten
      OGS biopsy specimens but in only one of six normal bone-derived specimens. Thus,
      tumor samples express both types (normal and the novel one) of UCP-2 mRNAs,
      whereas normal bone expresses only the wild-type form. Further experiments
      identified the novel mRNA species as an alternatively spliced UCP-2 transcript
      (termed UCP-2as). UCP-2as has a 22-nucleotide insertion from the 3' end of intron
      3 that introduces an early stop codon in exon 4, which theoretically can produce
      a protein 79 amino acids long. CONCLUSIONS: We have identified a hitherto unknown
      UCP-2 transcript. Expression of the novel transcript appears to be OGS-specific,
      implying a function advantageous to the tumor.

PMID- 16437350
TI  - Regenerated soft tissue survival using repulsive force of magnetized devices:
      preliminary report.
AB  - BACKGROUND: Large full-thickness cartilage defects in the weight-bearing area are
      difficult to treat. A new therapeutic strategy called the total joint
      regeneration (TJR) system is proposed for such large defects. The purpose of this
      study was to evaluate the effects of the magnet-type TJR device using a rabbit
      model. METHODS: The magnetized devices were implanted in full-thickness chondral
      defects on the patellofemoral joints of rabbits. The specimens and surrounding
      tissue were harvested 4 weeks after the surgery and observed macroscopically and
      histologically. The thickness of the regenerated soft tissue on the femur joint
      surface was measured and compared. The difference between the two groups
      (magnetized and nonmagnetized) was significant at P < 0.05. RESULTS: Some
      cartilaginous regeneration was seen in the repair tissue. However, about half of
      the experimental knees were omitted from the study because of some trouble, such
      as loosening of the device or patella fracture. CONCLUSIONS: This study suggested
      that magnetized devices were useful for regenerating soft tissue by maintaining
      the joint space. Some hyaline cartilage-like tissue was regenerated partially on
      the magnetized devices. It was suggested that these devices might be useful for
      cartilage regeneration if the devices are improved.

PMID- 16437351
TI  - Adenoviral gene transfer in the peripheral nervous system.
AB  - BACKGROUND: Viral vectors have gained widespread use as vehicles for somatic gene
      transfer, and the targeted expression of foreign proteins by these vectors offers
      advantages over the systemic administration of the drugs in some therapeutic
      situations. Selective virus-mediated gene transfer to the peripheral nervous
      system (PNS), however, remains to be established. There are no data showing
      efficiency of protein transduction in the PNS, which consists of a variety of
      cell types, many of which are postmitotic. METHODS: We prepared the first
      generation replication-deficient recombinant adenovirus vectors engineered to
      express LacZ. Eight-week-old Wister rats were used in this study. Adenovirus
      vector (5 microl) containing the LacZ gene (5 x 10(8) pfu) was injected into rat
      sciatic nerves or the dorsal root ganglia at the level of L5. The sciatic nerves,
      the dorsal root ganglia, and the spinal cords were obtained 7, 14, 21, and 28
      days after injection. Expression of LacZ was assessed by X-gal histochemistry and
      beta-gal immunohistochemistry. RESULTS: Following injection of the adenovirus
      carrying the LacZ gene into the sciatic nerve, LacZ expression was seen mainly in
      the Schwann cells and the small neurons in the dorsal root ganglion. In contrast,
      expression was observed in the primary nerve terminals of the spinal dorsal horn
      and the small to large dorsal root ganglion neurons and the Schwann cells after
      injection of the vectors into the L5 dorsal root ganglion. There were no side
      effects in rats with injection in the dorsal root ganglia or the sciatic nerve.
      CONCLUSIONS: The present study shows efficient protein transduction by adenovirus
      vectors in the PNS. It is noted that injection of the virus into the dorsal root
      ganglia leads to extensive expression of LacZ in the spinal cord, the dorsal root
      ganglia, and the sciatic nerves.

PMID- 16437352
TI  - Optimum surgical suture material and methods to obtain high tensile strength at
      knots: problems of conventional knots and the reinforcement effect of adhesive
      agent.
AB  - BACKGROUND: Strong suture material and a firmly tight knot that never loosens are
      necessary for tendon suture, but the appropriate combination of suture materials
      and the methods to make a knot are matters of uncertainty. METHODS: The tensile
      strength of four conventional tendon suture materials (Surgilon, Ethibond,
      Ethilon, PDS II) and newly developed FiberWire were examined. An experienced
      orthopedic surgeon formed surgical knots with USP2 wire (0.5-0.599 mm in
      diameter) by making loops and then pulled them at 20 mm/min using Instron.
      RESULTS: With the conventional surgical suture method (the addition of one throw
      on a surgeon's knot), Surgilon proved to have the highest tensile strength (163.6
      +/- 6.5 N). Other suture materials, when tied under the same conditions, slipped
      and did not reach the ultimate tensile strength. When four additional throws were
      made, FiberWire provided the highest tensile strength (316.6 +/- 12.2 N) among
      the five suture materials tested (others were 140-200 N). When an adhesive agent,
      cyanoacrylate, was applied to a knot, PDS II provided the highest tensile
      strength (182.0 +/- 10.1 N). CONCLUSIONS: Our study suggests three suitable
      combinations of suture materials and methods for suture knot formation, depending
      on the site of surgery, that provide optimum treatment outcomes. Surgilon
      provides the most stable strength for general suture techniques. FiberWire is the
      strongest suture material for a site where a large number of throws is clinically
      possible. PDS II provides a strong suture when combined with cyanoacrylate
      reinforcement.

PMID- 16437353
TI  - Pathogenesis of tendinous xanthoma: histopathological study of the extremities of
      Watanabe heritable hyperlipidemic rabbits.
AB  - BACKGROUND: Tendinous xanthomas associated with heritable hyperlipidemia are
      clinically well known. Nevertheless, there have been few basic investigations of
      the pathogenesis of these xanthomas. To clarify the pathogenesis of these
      xanthomas, we examined the localization and histopathological features of
      xanthomatous tissues in the extremities of Watanabe heritable hyperlipidemic
      (WHHL) rabbits. METHODS: Twenty-six WHHL rabbits at 1-31 months of age were
      dissected to observe the localization of xanthomas. In the histopathological
      study, tendons and ligaments that included xanthomatous tissues were sectioned
      and stained with hematoxylin and eosin, Masson's trichrome, and toluidine blue.
      Immunohistochemical staining was performed with RAM-11, a monoclonal antibody
      specific for rabbit macrophages, and CD31, a monoclonal antibody specific for
      endothelial cells. RESULTS: At necropsy examination, spontaneous development of
      xanthomas was observed in the plantar side of the plantaris tendon, the flexor
      retinaculum of the carpus, and around the digital flexor tendons of each joint
      level. Xanthoma formation was observed from 10 months of age and progressed with
      advancing age. The histomorphological study revealed that xanthomas had developed
      in superficial paratenon of the tendons that wrap around bony or fibrous pulleys.
      Many fibrocartilage cells were observed in the deep side of affected tendons. A
      large number of blood vessels were seen in the xanthomatous tissues of these WHHL
      rabbits. Immunohistochemical evaluation revealed that the xanthoma plaques
      contained endothelial cells and macrophages. CONCLUSIONS: It is likely that
      mechanical stress and extensive vascularization are essential factors for
      xanthoma formation. Moreover, endothelial cells and macrophages cells are
      principal contributors to the pathogenesis of tendinous xanthomas and to
      atherogenesis.

PMID- 16437354
TI  - Lumbar discal cyst followed by intervertebral disc herniation: MRI findings of
      two cases.

PMID- 16437355
TI  - Vibrio vulnificus infection of the hand.

PMID- 16437356
TI  - Common peroneal nerve palsy caused by parosteal lipoma of the fibula.

PMID- 16437357
TI  - Long-term survival of soft tissue sarcoma patients with extrapulmonary
      metastasis.

PMID- 16437358
TI  - Revision of acrylic hinge-type knee prosthesis after a follow-up of almost 40
      years.

PMID- 16437359
TI  - Skin defects covered using medialis pedis flaps after correction of severe
      flexion contracture of the big toes due to plantar fibromatosis.

PMID- 16437360
TI  - Median nerve entrapment at the volar stump of the proximal radial fragment in
      Colles' fracture.

PMID- 16437361
TI  - Takayasu's arteritis presenting with bilateral pulmonary granulomatosis.
AB  - Takayasu's arteritis (TA) is a vasculitis characterized by inflammation and
      obliteration of intermediate to large-size arteries. We report a case of
      Takayasu's arteritis with a presentation of bilateral pulmonary nodular
      infiltrates in a 21-year-old man. An open-lung biopsy showed characteristic
      changes of extra-vascular granulomatosis. To our knowledge, this has not been
      described previously in the literature.

PMID- 16437362
TI  - Prevalence and classification of headache in patients with systemic lupus
      erythematosus.
AB  - Studies on the prevalence of headache in systemic lupus erythematosus (SLE) have
      shown that it varies from 32 to 78%. The purpose of our study was to determine
      the prevalence and characteristics of headache in SLE compared with patients with
      different types of diffuse connective tissue diseases (DCTD) and its relationship
      with clinical and laboratory manifestations of SLE. We studied patients with SLE
      (SLE group) and patients with DCTD (control group). All patients were made to
      answer questionnaire to assess the presence of headache, characterized by at
      least five episodes of headache during the last year, which was classified
      according to the International Headache Society criteria. A total of 207 patients
      were studied, 115 in SLE group and 92 in the control group. The 1-year prevalence
      of headache was 75.7% in SLE group and 66% in the control group. When the groups
      were analyzed, 66.1% met the diagnostic criteria for migraine in the SLE group
      compared with 52.2% in the control group (p=0.04) and 13.9% for tension-type
      headache in SLE group compared with 16.3% in the control group. The former was
      the only variable that reached statistical significance comparing the two groups.
      Both headache and migraine were associated with Raynaud's phenomenon in SLE
      patients (odds ratio of 2.80, 95% confidence interval: 1.11-7.05, p=0.02 and odds
      ratio of 2.34, 95% confidence interval: 1.04-5.23, p=0.03, respectively). These
      results suggest that headache is a common manifestation in SLE and in other DCTD
      and we cannot exclude the possibility that it may be related to the emotional
      stress induced by such clinical situations.

PMID- 16437363
TI  - Dermatomyositis complicated with Kaposi sarcoma: a case report.
AB  - We describe the case of a 75-year-old Italian woman affected by dermatomyositis
      (DM) treated with steroid, high-dose intravenous immunoglobulins (IVIgs) and
      cyclophosphamide (CPX), taken orally. After a few months, the patient presented
      multiple red vascular skin lesions diagnosed as Kaposi sarcoma (KS). Steroid was
      furtherly reduced, and CPX was stopped. We put the patient on chemotherapy with
      intravenous infusion of vinblastine and vincristine on alternate weeks obtaining
      the remission of KS. DM is well controlled by a low-dosage steroid and high-dose
      IVIgs.

PMID- 16437364
TI  - [Disciplinarian of lymph node metastasis and effect of paraaortic lymph nodes
      dissection on clinical outcomes in advanced gastric carcinoma].
AB  - OBJECTIVE: To investigate the disciplinarian of lymph node metastasis and
      evaluate the effect of paraaortic lymph nodes dissection on the clinical outcomes
      in advanced gastric carcinoma. METHODS: One hundred and twenty-six patients who
      underwent D(3) (including D(3)(+)) radical resection (group D(3)) and 146
      patients who underwent D(2) radical resection by the same surgical team (group
      D(2)) for advanced gastric cancer were enrolled in the present study. The
      dissected lymph nodes were grouped according to the definition of Japanese
      Research Society for the Study of Gastric Cancer (JRSGC) (Edition 13th). The
      lymph node metastasis was analyzed in group D(3). The clinicopathological
      characteristics and clinical outcomes were compared between the two groups.
      RESULTS: There were no differences in age, sex, tumor location, Borrman type,
      histological type and TNM stage between group D(2) and group D(3) (P > 0.05). The
      No16 lymph node metastatic rate was 3.8%, 22.3%, 46.8% and 32.1% in T(1), T(2),
      T(3), T(4) stage tumors respectively, 16.3% and 69.5% in the patients with
      negative and positive serosal invasion respectively; there were no differences in
      operative mortality (2/126 vs 2/146) and surgical complications (4/126 vs 6/146)
      between group D(2) and group D(3) (P > 0.05). The 5-year survival rate was 66.5%
      in group D(3) and 40.2% in group D(2) (P< 0.01). The 5-year survival rates of the
      patients with I, II, IIIa, IIIb and IV stage tumors who were No16 lymph nodes
      negative were 94.8%, 95.6%, 72.1%, 58.6%, 59% respectively in group D(3), and
      42%, 36%, 27%, 35.6%, 16.3% respectively in group D(2). The 5-year survival rate
      of the patients with No16 (+) lymph nodes less than 3 was higher than that of the
      patients with No16(+) lymph nodes more than 3. CONCLUSIONS: No16a2 and No16b1 are
      the common locations of lymph node metastasis in advanced gastric cancer. The
      paraaortic lymph node metastasis closely is related with the depth of tumor
      invasion and serosal invasion. Paraaortic lymph nodes dissection (D(3) or D(3)(+)
      radical resection) improves the 5-year survival rate of the patients with No16 (
      ) and No16 (+) lymph nodes less than 3.

PMID- 16437365
TI  - [Comparison of two reconstruction methods of alimentary canal after total
      gastrectomy].
AB  - OBJECTIVE: To evaluate the clinical value of two alimentary reconstruction
      methods after total gastrectomy for gastric cancer. METHODS: Thirty- one patients
      undergoing total gastrectomy for gastric cancer were prospectively randomly
      divided into two groups: single-canal jejunum interposition (n=16, group A) and P
      pouch with Roux-en-Y esophagojejunostomy (n=15, group B). All patients were
      followed up for one year. The serum nutritional parameters,body weight change and
      clinical effects between the two groups were compared. RESULTS: Both of the
      reconstruction types had the replacement of gastric function. The hemoglobin
      level was (102+/- 11)g/L, the total protein level (6.8+/- 3.9)g/L, and the body
      weight loss (1.0+/- 1.7)kg in group A, while (98+/- 12)g/L, (6.3+/- 3.0)g/L and
      (4.0+/- 2.3)kg in group B. There were significant differences between the two
      groups (all P< 0.05). CONCLUSION: The single-canal jejunum interposition
      reconstruction after total gastrectomy (Henley) is a better surgical method.

PMID- 16437366
TI  - [Clinical effect of intraoperative peritoneal hyperthermic chemotherapy for
      advanced gastric cancer].
AB  - OBJECTIVE: To investigate the clinical effect of intraoperative peritoneal
      hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC). METHODS: A
      total of 118 AGC patients with serosal invasion were enrolled in this study from
      1998 to 2001. Among these cases, 96 patients without macroscopic peritoneal
      metastases were selected for prophylactic study, including 42 cases with IPHC and
      54 cases without IPHC as control. Other 22 patients with macroscopic peritoneal
      metastases were selected for therapeutic study, including 10 cases with IPHC and
      12 without IPHC. Postoperative survival rate and peritoneal recurrence were
      compared. RESULTS: For prophylactic study, the 1, 2 and 4 years survival rates
      were 85.7%, 81.0% and 63.9% respectively in the patients with IPHC,significantly
      higher than 77.3%, 61.0% and 50.8% in the patients without IPHC. Cox ratio hazard
      model revealed that IPHC procedure was an independent prognostic factor. More
      patients in the control group suffered from peritoneal recurrence than those in
      IPHC group (34.7% vs 10.3%). For therapeutic study,the median survival period of
      the patients with IPHC was 10 months, higher than 5 months in the patients
      without IPHC. The overall 1, 2, 4 year survival rates were 76.9%, 69.2%, 55.2%
      respectively in all cases with IPHC, higher than 66.2%, 49.7%, 41.4% in the cases
      without IPHC. CONCLUSION: IPHC procedure can improve the prognosis of AGC
      patients with serosal invasion, reduce the risk for peritoneal recurrence, and is
      an independent prognostic factor.

PMID- 16437367
TI  - [Risk factors of elderly patients with total gastrectomy for gastric cancer].
AB  - OBJECTIVE: To analyze the relative risk factors of elderly patients with total
      gastrectomy for gastric cancer. METHODS: The risk factors for hospital death and
      postoperative complications in 131 elderly patients undergoing total gastrectomy
      for gastric cancer from Aug. 1994 to Aug. 2004 were analyzed retrospectively.
      RESULTS: The risk factors for hospital death and postoperative complications
      included coexistent diseases, hemoglobin level less than 80 g/L, albumin level
      less than 35 g/L, body mass index(BMI) less than 18.5 kg/m (2), intraoperative
      blood loss more than 1000 ml, operating time longer than 5 h, combined resection
      of the spleen or pancreas. The relative risks were 1.57, 1.74, 2.97, 4.23, 2.21,
      2.28, 3.80 respectively for hospital death, and 1.50, 1.90, 2.38, 2.12, 2.45,
      1.66, 3.41 for postoperative complications. CONCLUSION: The risk factors of the
      elderly patients with total gastrectomy for gastric cancer should be considered
      carefully during the perioperative period. It can increase the security of the
      procedure to control these risk factors.

PMID- 16437368
TI  - [Peripheral plasma Big endothelin 1 levels in patients with gastric carcinoma
      undergoing radical gastrectomy and its relationship with tumor recurrence].
AB  - OBJECTIVE: To investigate the plasma Big endothelin-1 levels in patients with
      gastric carcinoma before and after radical gastrectomy, and explore its clinical
      significance. METHODS: One hundred and six patients with gastric carcinoma and 20
      controls were enrolled. The Big ET-1 plasma levels were examined by enzyme-linked
      immuno absorbent assay before and on the 1st, 3rd, and 10th day after curative
      surgery, and then were tested every 3 months in the patients with advanced
      gastric cancer. RESULTS: All patients, except those with stage I gastric cancer,
      had significantly higher mean plasma Big ET-1 levels compared with normal
      controls (P=0.000). Higher plasma Big ET-1 levels were associated with lymph node
      metastasis (P=0.020) and serosal infiltration (P=0.035). The plasma Big
      Endothelin-1 levels were markedly increased on the first post-operative day (1st
      POD) in all patients,but decreased on the 3rd POD with no significant difference
      compared to the preoperative levels. On the 10th POD, the patients with stage I
      and II gastric cancer showed marked reduction in plasma Big ET-1 levels (P=0.010
      and P=0.000, respectively), whereas no significant difference was observed in
      stage III and IV patients. During the follow-up, the plasma Big ET-1 levels just
      before recurrence in stage II patients were significantly higher compared with
      the levels on the 10th POD (P=0.011). CONCLUSIONS: Plasma Big ET-1 might be a
      reliable marker to determine the severity of gastric carcinoma. Monitoring plasma
      Big ET-1 levels after curative resection in stage II gastric cancer patients is
      valuable to predict recurrence.

PMID- 16437369
TI  - [Benign gastric strictures after transthoracic esophagectomy and
      esophagogastrostomy: an analysis of 9 cases].
AB  - OBJECTIVE: To investigate the manifestations,etiology,diagnosis and treatment of
      benign gastric strictures after transthoracic esophagectomy and
      esophagogastrostomy. METHODS: From January 1998 to December 2004, 9 cases with
      benign gastric strictures following esophagectomy were enrolled in the study. The
      manifestations,radiographic and endoscopic findings, treatment were analyzed
      retrospectively. RESULTS: The patients included 8 males and 1 female. Benign
      gastric stricture is characterized by mucosa absence and proliferation of fibrous
      tissue in the stomach below the stoma. The age ranged from 49 to 71 years old
      (median age 62). The common symptom was postoperative dysphagia. The length of
      stricture ranged from 1.5 to 5.0 cm, and the width from 0.1 to 0.5 cm. Seven
      cases were treated ineffectively with simple dilation,while esophageal stent
      placement was performed in 8 cases successfully. After follow- up from 5 to 60
      months, restenosis occurred for 11 times including stent fall-off for 6
      times,stent migration for 1 times, overgrowth of granular tissues for 4 times.
      Other complications included cervical incision infection and massive hemorrhage
      in one case respectively. Restenoses were all solved with stent replacement.
      CONCLUSIONS: Benign gastric stricture should be diagnosed through dysphagia,
      barium meal and endoscopy. Placement of non-self-expandable stent or whole
      covered self-expandable metallic stent is the primary treatment.

PMID- 16437370
TI  - [Study of gastric function after esophagectomy and cardiectomy with vagus nerve
      preserved and reconstruction of gastric funds in patients with esophageal and
      cardiac cancer].
AB  - OBJECTIVE: To study the gastric function after esophagectomy and cardiectomy with
      vagus nerve preserved and reconstruction of gastric funds (VPRG)in patients with
      esophageal cancer (EC) and cardiac cancer (CC). METHODS: Sixty-eight patients
      with early or middle staged EC or CC received esophagectomy and cardiectomy with
      vagus nerve preserved and reconstruction of gastric funds (VPRG),while other 68
      patients esophagectomy and cardiectomy with vagus nerve severed and no
      reconstruction of gastric funds (VSNG) as control. The symptoms,the pressure of
      the residual esophagus and thoracic stomach, 24-hour pH monitoring, mean basic
      gastric acid output, gastric emptying time of the intrathoracic stomach,fasting
      serum gastrin level, fibreoptic endoscopic results were compared before and after
      operation between the two groups. RESULTS: The patients with VPRG had less
      symptoms after operation than those with VSNG such as anorexia, belch, reflux,
      heartburn, nausea, diarrhea, postcibal satiety (P< 0.01). In VPRG group,compared
      with the results before operation,there were no significant differences in 24
      hour pH monitoring,the mean basic gastric acid output, the fasting serum gastrin
      level,the gastric emptying time of intrathoracic stomach one month and one year
      after operation (both P > 0.05). The pressure of the residual esophagus above the
      anastomosis in VPRG group was significantly higher than that in VSNG group (both
      P< 0.05). Fibreoptic endoscopic examination revealed higher incidences of
      postoperative atrophic gastritis and reflux esophagitis in VPRG group one month
      and one year after operation than those in VSNG group (P< 0.01). CONCLUSION:
      Preservation of the vagus nerve and reconstruction of gastric funds after
      esophagectomy and cardiectomy for esophageal and cardiac cancer can prevent
      digestive disorder and improve the life quality of the patients.

PMID- 16437371
TI  - [Endoscopic interventional treatment of malignant gastrointestinal obstruction].
AB  - OBJECTIVE: To evaluate the feasibility and clinical value of endoscopic
      interventional treatment of malignant gastrointestinal obstruction. METHODS: With
      the aid of X ray, 32 cases with malignant gastrointestinal obstruction were
      treated with endoscopic metal stenting. There were 8 cases with gastric outlet
      obstruction, 7 with duodenal obstruction, 13 with rectal obstruction, and 4 with
      sigmoid obstruction. RESULTS: Among the 32 patients, metal stenting was
      successfully performed in 30 cases (93.7%, and obstructive symptoms were relieved
      within 1-3 days. Metal stent placement was permanent in 15 cases with gastric
      outlet or duodenal obstruction. Twelve cases with colorectal obstruction received
      stent placement as palliative treatment, while other 3 cases underwent subsequent
      elective surgical resection. Metal stent placement failed in one case with
      recurrent rectal carcinoma, and perforation occurred in another one case with
      wide spread metastatic sigmoid colon carcinoma and Hartmann operation was
      performed. During the follow-up period, no stent migration was detected.
      CONCLUSION: Endoscopic interventional treatment of malignant gastrointestinal
      obstruction is a feasible, safe, effective and well tolerated method. It can
      reduce the patients trauma and pain, and improve the quality of life.

PMID- 16437372
TI  - [Clinical application of vacuum pack system for temporary abdominal closure].
AB  - OBJECTIVE: To investigate the clinical application of a new temporary abdominal
      wound closure,vacuum system for temporary management of the open abdomen.
      METHODS: Vacuum pack system consisted of polyethylene sheet,surgical
      towel,silicone drain, adhesive plastic drape. Clinical data of the patients
      undergoing exploratory celiotomy were recorded,and the indications for such
      temporary abdominal closure and its complications were reviewed. RESULTS:
      Thirteen trauma patients underwent such vacuum abdominal closure for 15 times,
      including 5 times (33.3%) for increased intra- abdominal pressure so that tension
      free fascial closure was unable to achieve, 4 times (26.7%) for reexploration, 2
      times (13.3%) for damage control, and 4 times (26.7%) for combined factors.
      Finally, seven patients (53.8%) received direct closure and 5 patients (38.5%)
      received skin grafting after granulation because the defect could not be closed
      directly. One patient (7.7%) died before abdominal closure was attempted. None of
      the patients developed enterocutaneous fistula and evisceration. Three patients
      (23.1%) developed intra-abdominal abscess. CONCLUSIONS: The vacuum pack is a
      better temporary abdominal wound closure device, and primary closure can be
      achieved in most of the patients. The technique is simple and easily mastered
      with a low complication rate.

PMID- 16437373
TI  - [Diagnosis and surgical management of adult Hirschsprung disease].
AB  - OBJECTIVE: To investigate the diagnosis and surgical treatment of adult
      Hirschsprung disease (AHD). METHODS: Clinical data of 10 patients with AHD
      undergoing operation from May 1985 to May 2005 were analyzed retrospectively.
      RESULTS: There were 7 males and 3 females with an age ranged from 14 to 40 years.
      All the cases had constipation, and were diagnosed by barium enema. Aganglionosis
      was located in distal sigmoid and rectum in 2 cases, in rectum in 7 cases,
      unknown in one case. Colostomy was performed in one, Ikeda s operation in 6,
      Rehbein operation in two,modified Swenson operation in one. After radical
      operation,7 patients had excellent continence function, one had good function,
      one had poor function. CONCLUSIONS: The diagnosis of adult HD mainly depends on
      the history of constipation, barium enema and manometry examination. The pull
      through procedures are effective surgical treatments for adult HD. The operation
      type should be selected individually.

PMID- 16437374
TI  - [Clinical value of positron emission tomography-CT for the diagnosis of
      postoperative recurrence and metastasis in the patients with esophageal cancer].
AB  - OBJECTIVE: To evaluate the clinical value of the whole-body (18)F-fluoro-deoxy-D
      glucose positron emission tomography with computerized tomography (PET-CT) for
      recurrence and distant metastasis after curative resection of the esophagus
      cancer. METHODS: From June 2003 to June 2004, thirty-one patients with clinical
      or radiologic suspicion of recurrent disease underwent conventional diagnostic
      work-up, including a spiral CT scan, and a dedicated whole-body PET-CT. All cases
      were examined by pathology or followed-up for 6 months. RESULTS: Among the 31
      cases, recurrences were found in 23 patients, and 43 recurrent lesions were
      detected, including 14 perianastomotic lesions and 43 regional and distant
      lesions. For the diagnosis of recurrence, the accuracy, sensitivity and
      specificity of PET-CT were 97.7%, 100%, and 85.7%, while those of conventional CT
      were 77.3%, 61.7%, and 78.6% respectively. The sensitivity of PET-CT was
      significantly higher than that of conventional CT (100% vs 61.7%; chi (2)=4.161,
      P=0.041). CONCLUSIONS: The sensitivity of PET-CT is higher than that of
      conventional CT. PET-CT will play an important role in the diagnosis of
      postoperative recurrence and metastasis of esophageal cancer.

PMID- 16437375
TI  - [Protective effect of glutamine on intestinal barrier function in patients
      receiving chemotherapy].
AB  - OBJECTIVE: To study the protective effect of glutamine (Gln) on intestinal
      permeability in patients receiving chemotherapy. METHODS: Thirty-nine patients
      with gastrointestinal cancer after operation were randomly divided into Gln and
      control groups, and received oral administration of glutamine (30 g/d) for 7 days
      (n=22) or not (n=17). All patients received CF+ 5-FU chemotherapy for 5 days.
      Serum concentration of glutamine and urinary lactulose/mannitol (L/M) ratio were
      measured before and 1 day after chemotherapy. RESULTS: After chemotherapy, the
      serum Gln concentration was significantly decreased to (535.42+/- 53.75)
      micromol/L in the control group and increased to (54.44+/- 81.26) micromol/L in
      the Gln group, and there was significant difference between the two groups (P<
      0.01). Urine L/M ratio was significantly increased to (0.0453+/- 0.0078) in the
      control group and decreased to (0.0331+/- 0.0061) in the Gln group, and there was
      significant difference between the two groups after chemotherapy (P< 0.01).
      CONCLUSION: Oral administration of glutamine granules can increase serum
      concentration of glutamine in chemotherapy patients with gastrointestinal cancer
      and can decrease intestinal permeability, maintain intestinal barrier.

PMID- 16437376
TI  - [Inhibition of polo like kinase gene expression induces apoptosis in gastric
      cancer cells].
AB  - OBJECTIVE: To observe the effect of inhibition of polo like kinase1 (plk1) gene
      expression on apoptosis induction in gastric cancer cell line-MKN45 and discuss
      the vital role of plk1 proliferation and viability of gastric cancer cells.
      METHODS: The plk1 expression was inhibited by chemically synthesized siRNA. The
      plk1 mRNA and protein level were respectively measured by real-time quantitative
      PCR and Western blotting. The spindle morphological change was observed by
      immunofluorescence staining and confocal microscopy. The change of cell cycle
      distribution and apoptosis rate was detected by flow-cytometry. Pro caspase3
      level was also detected by western blotting. RESULTS: After treatment by siRNA
      targeting plk1, plk1 mRNA and protein level decreased obviously, the cell mitotic
      spindle became obscure and lost cohesiveness, more MKN45 cells accumulated at
      G(2)/M phase (P< 0.05), apoptosis rate of plk1 siRNA treated MKN45 cells was
      higher than that of control cells at 48 h and 72 h (P< 0.05) with pro-caspase3
      level decreasing at 72 h. CONCLUSIONS: Inhibition of plk1 gene expression induces
      apoptosis in MKN45 cells through the pathway of caspase3. Plk1 gene play a key
      role in viability of MKN45 cells.

PMID- 16437377
TI  - [Effect of glucagon-like peptide 2 on the intestinal mucosal immunity and
      correlative cytokines in mice with gut ischemia/reperfusion injury].
AB  - OBJECTIVE: To investigate the effect of glucagon- like peptide 2 on intestinal
      mucosa immunity after ischemia/reperfusion injury and explore the possible
      mechanisms. METHODS: A total of 70 ICR mice were randomly divided into three
      groups including normal control group(N), I/R group(C) and GLP-2 treatment
      group(T) (treated with GLP-2,200 microg/kg). The mice were sacrificed on the 1st,
      3rd and 5th day after I/R injury. Liver,spleen and mesenteric lymph nodes samples
      were collected for bacterial culture. The endotoxin levels in plasma were also
      measured. Small intestine washing were obtained for IgA and the intestine
      homogenized were analyzed for Th1/Th2 cytokines. RESULTS: The rate of bacterial
      translocation and the level of endotoxin in group C were significant higher than
      those in group T and group N. The IgA level in the lavage of the intestine was
      significantly decreased on the 1st day after I/R in group C and T compared with
      that in group N, while there was no difference between group C and T. The IgA
      level increased on the 3rd day and returned to normal on the 5th day after I/R in
      group T, while that in group C was still lower than normal. In group C, the
      levels of Th1-type (IL-2 and IFN-gamma) cytokines increased, the levels of Th2
      type (IL-4 and IL-10) decreased significantly on the 1st day and then increased
      gradually. The change pattern of cytokines levels in group T resembled that in
      group C, but the levels of IL-4 and IL-10 in group T returned to normal on the
      5th day after I/R. CONCLUSIONS: GLP-2 supplementation can partly protect the
      intestinal mucosal immunity. The mechanism may probably be related to the
      restitution of the balance of Th1/Th2 cytokines in the intestinal mucosa in mice.

PMID- 16437378
TI  - Clinicopathological study of metallothionein immunohistochemical expression, in
      benign, borderline and malignant ovarian epithelial tumors.
AB  - Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which
      are expressed in normal cells during fetal and postnatal life but also in a
      variety of human neoplasms. MT expression in human tumors has been linked to
      resistance to anticancer drugs and differentiation and progression in some types
      of tumors. This study examined the immunohistochemical expression of MTs in
      benign, borderline and malignant tumors of ovarian surface epithelium and the
      possible correlations with clinicopathological parameters and survival. A total
      of 87 cases with diagnosis of ovarian surface epithelial tumors were included.
      Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14
      borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases
      of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off
      level > 10% of tumor cells) was clearly associated with malignancy. A
      statistically significant correlation was found between the expression of MT in
      cancer cases and benign tumors (p < 0.0001) and cancer cases and borderline
      tumors p = 0.003. In cancer cases a difference was observed between grade I and
      III (p = 0.002). There was no correlation of MT overexpression with survival in
      the small number of ovarian carcinoma patients where it was analysed. MT
      constitutes a marker that characterizes aggressiveness and a high malignant
      potential in ovarian epithelial tumors. In diagnostic problems MT may help
      distinguish between benign, borderline and malignant tumors.

PMID- 16437379
TI  - The distribution pattern of myofibroblasts in the stroma of human bladder
      carcinoma depends on their invasiveness.
AB  - The presence of myofibroblasts has been elucidated in the stroma of neoplasm of
      various organs. In the present article, we studied the distribution of
      myofibroblasts in the stroma of bladder carcinoma. Twenty-five surgical resected
      bladder tumors (urothelial carcinoma, n = 21; combined urothelial carcinoma and
      adenocarcinoma, n = 2; sarcomatoid squamous cell carcinoma, n = 1; combined
      urothelial carcinoma and squamous cell carcinoma, n = 1) were selected and we
      evaluated the distribution of myofibroblasts using immunohistochemical, electron
      and immunoelectron microscopic techniques. Immunohistochemically, the
      distribution pattern of myofibroblasts in invasive and non-invasive carcinomas
      were predominantly fascicular and reticular forms, respectively. Moreover,
      myofibroblasts around bladder carcinoma cells were confirmed by electron
      microscope. Understanding the distribution pattern of myofibroblasts in the
      stroma of bladder carcinoma may provide available information about the presence
      of carcinoma invasion.

PMID- 16437380
TI  - Morphological and immunocytochemical characterization of snake-like chromatin
      cells.
AB  - Snake-like chromatin (SLC) is a nuclear alteration occurring under various
      pathological conditions and in different tissues. The aim of this study was the
      morphological and immunocytochemical characterization of SLC-positive
      conjunctival epithelial cells from keratoconjunctivitis sicca (KCS) patients.
      Impression cytology specimens from the upper bulbar conjunctiva of 10 controls
      and 10 KCS patients with a high incidence of SLC cells were assessed, the
      morphology of SLC nuclei evaluated by light microscopy, and proliferation
      markers, nucleolar proteins, lamins and cytokeratin filaments detected
      immunocytochemically. In KCS patients, SLC cells with a normal nuclear shape,
      with nuclear membrane notching (2.3% of cells) and with binuclear dumb-bell
      structures (4.4% of cells) were observed. The most striking features of SLC cells
      were the absence of an A/C lamin signal, the redistribution of fibrillarin into
      two spots adjacent to SLC structures and cytokeratin 14 positivity in the
      strangulation belt of the dumb-bell structures. The deficiency of lamin A/C is
      the probable reason for the disintegration of chromatin from the nuclear lamina
      in SLC cells. The occurrence of SLC-positive cells, SLC-positive dumb-bell shaped
      nuclei and SLC-positive binucleated cells, together with the absence of mitotic
      markers, leads to the conclusion that the SLC phenomenon might be a form of
      nuclear segregation.

PMID- 16437381
TI  - Apolipoprotein D expression in substantia nigra of Parkinson disease.
AB  - Apolipoprotein D (apo D), a lipocalin transporter of small hydrophobic molecules
      could play an important role in several neurodegenerative diseases. However, its
      role in those diseases remains unclear. Increments of apo D have been reported in
      relation with injury and degeneration in the nervous system. Recently increases
      of apo D level have been reported in schizophrenia, a neuropathologic disease
      where the oxidative stress and lipid abnormalities may be involved. Apo D could
      act as a sequestering molecule binding excess of arachidonic acid in cells. In
      order to determine the relationship between apo D expression and other
      neurodegenerative pathologies related to oxidative damage, we studied the
      presence of apo D in the substantia nigra of control and Parkinson disease (PD)
      subjects. We found dopaminergic neurons were not immunoreactive for apo D,
      control or PD subjects. However, surrounding glial cells showed immunostaining
      for apo D and signal increases in PD cases. These findings support the role of
      apolipoprotein D in neuroprotection and the importance of glia in the amount of
      this protein in the central nervous system.

PMID- 16437382
TI  - The effect of oestradiol and neta on immunohistochemical staining of iNOS and
      eNOS in coronary arteries of ovariectomized rats.
AB  - AIM: The postmenopausal period is associated with increased risk for coronary
      atherosclerosis, and the effect of hormone replacement therapy in reducing this
      risk is controversial. Previous studies reported that nitric oxide synthetase
      (NOS) level might be important for the development of atherosclerosis, but no
      study has shown the interaction between hormone replacement therapy and
      endothelial NOS and inducible NOS intensity on coronary arteries yet. Our goal
      was to find out the immunostaining intensity of endothelial NOS and inducible NOS
      in ovariectomized rats which received oestradiol and norethisterone treatment.
      METHODS: We performed bilateral ovariectomy in 15, female, 90-day-old Wistar rats
      with an average weight of 250 grams. After waiting for 4 weeks for the menopausal
      state, they were divided into 3 groups to receive either placebo, 0.1 mg/day 17
      beta-oestradiol (group E2), or 0.1 mg/day 17-beta-oestradiol + 0.1 mg/day
      norethisterone acetate (group E2-NETA) for 5 weeks. Another group included 5,
      normal, adult, female intact rats and served as controls. At the end of the
      treatment, all rats were sacrificed and coronary arteries were stained with
      inducible NOS and endothelial NOS polyclonal antibodies using streptavidin-biotin
      technique. RESULTS: The immunostaining of inducible NOS was prominent in
      perivascular connective tissue of the ovariectomized group but not in the control
      group. The inducible NOS immunostaining immunoreactivity was not detected in
      either treated groups. Immunostaining intensity of endothelial NOS did not differ
      in any 4 groups with similar staining. CONCLUSION: The present findings indicate
      that hormone replacement therapy down-regulates iNOS expression in coronary
      arteries of ovariectomized rats, and reduced iNOS may likely be involved in
      estrogen's beneficial effects.

PMID- 16437383
TI  - Expression of checkpoint kinase 2 in breast carcinomas: correlation with key
      regulators of tumor cell proliferation, angiogenesis, and survival.
AB  - Checkpoint kinase 2 (Chk2) is a cell-cycle-checkpoint kinase that may act as a
      tumor suppressor gene due to its important role in DNA damage signaling and cell
      cycle regulation. The role of Chk2 expression in mammary tumorigenesis, however,
      is still poorly understood. This study was designed to assess the relationship
      between the expression of Chk2 and well-established prognostic factors, including
      disease-free-survival and overall survival; and several regulators of cell
      proliferation and invasiveness in breast carcinomas, including oncogenes, tumor
      suppressor genes, apoptosis-related proteins, and angiogenesis-related markers.
      Immunohistochemistry with 27 primary antibodies was performed in 100 formalin
      fixed paraffin-embedded samples of not otherwise specified invasive ductal
      carcinomas. Clinical data were retrieved from medical files. In normal mammary
      parenchyma adjacent to the tumors Chk2 stained the nuclei of epithelial cells.
      Downexpression of Chk2 protein was observed in 23 carcinomas and correlated with
      advanced disease. Among the regulators of tumor cell proliferation and
      invasiveness analyzed, the downexpression of Chk2 correlated only with reduced
      expression of p27 and telomerase. There was no difference between the overall
      survival and disease-free survival rates according to Chk2 status. In conclusion,
      Chk2 correlated with reduced expression of h-TERT and p27, but not with
      angiogenic factors. Chk2 expression also did not interfere in the outcome of the
      patients.

PMID- 16437384
TI  - Partial urethral obstruction enhances NADPH-diaphorase activity in the monkey
      (Macaca fascicularis) bladder: light and electron microscopic studies.
AB  - The effect of partially obstructing the urethra on the nicotinamide adenine
      dinucleotide phosphate-diaphorase (NADPH-d) activity in neurons of the intramural
      ganglia of the monkey (Macaca fascicularis) bladder was examined by light and
      electron microscopy. Partial urethral ligation was done in adult male monkeys.
      The animals were sacrificed 2, 4 weeks after partial urethral obstruction. This
      was compared to controls (normal and sham operated). Urethral obstructed animals
      were observed to have increased urinary frequency and decreased urinary flow
      rate. Two weeks after urethral obstruction, the overall NADPH-d activity in the
      intramural ganglia of the bladder base was enhanced compared to control animals.
      The frequency of intensely stained NADPH-d positive neurons was increased
      compared to the control animals. About one-third of intensely stained NADPH-d
      positive neurons appeared to undergo degenerative changes. At 4 weeks after
      urethral obstruction, a wide occurrence of NADPH-d positive neurons in advanced
      stages of degeneration in the bladder base was observed. Cellular debris was
      strewn among normal looking ganglion cells and along the nerve processes. The
      proportion of intensely stained NADPH-d positive neurons was relatively lower
      than the controls. The total number of NADPH-d positive neurons and the nerve
      fibres in the entire bladder was significantly reduced when compared to control
      animals. Electron microscopy showed some NADPH-d activity in intramural ganglion
      cells in 2 weeks after partial urethral obstruction. NADPH-d reaction product
      (formazan) was deposited on the membranes of the rough endoplasmic reticulum, and
      the outer membranes of some mitochondria in the intramural neuron. At 4 weeks
      after urethral obstruction, NADPH-d was present in the membrane of the
      mitochondria and some mitochondria appeared swollen with disrupted cristae.
      Present results show that NADPH-d activity in neurons of the intramural ganglia
      of the monkey (Macaca fascicularis) urinary bladder was increased after two weeks
      and reduced after 4 weeks of partial urethral obstruction. It is speculated that
      the increased NADPH-d activity associated with partial urethral obstruction would
      lead to neuronal damage and death, which may contribute to detrusor overactivity.
      However, it warrants further investigation to understand the mechanism of
      neuronal cell death after partial urethral obstruction.

PMID- 16437385
TI  - Detection and localization of HIV-1 DNA in renal tissues by in situ polymerase
      chain reaction.
AB  - The localization of HIV-1 DNA in renal tissues is critically important for
      understanding pathogenesis of HIV-associated nephropathy (HIVAN), but the
      clarification has been technically challenging. We applied in situ polymerase
      chain reaction (IS-PCR) to human renal tissues to demonstrate viral entry into
      the renal epithelial cells in vivo. To test the specificity of this method and to
      determine the cell types infected, we used IS-PCR followed by in situ
      hybridization (ISH) and IS-PCR followed by immunohistochemistry and histochemical
      counterstains. Brief 2 hour fixation in 4% paraformaldehyde had 92.9% sensitivity
      and 100% specificity for detection of viral DNA in renal biopsies of HIVAN
      patients, compared to 70.8% sensitivity and 66.7% specificity in renal biopsies
      fixed overnight in 10% formalin. Under optimized conditions, the only signals
      detectable in HIV-1 seronegative cases were false positives attributable to renal
      tubular apoptosis. In HIVAN cases, positive signal was observed in podocytes,
      parietal cells, renal tubular cells, and interstitial leukocytes.
      Immunohistochemical co-labeling for pan-T cell and macrophage markers revealed
      that the interstitial leukocytes with positivity for HIV-1 DNA included both T
      cells and macrophages. Application of ISH after IS-PCR showed the same
      distribution of signal as observed using IS-PCR alone, confirming the specificity
      of the technique. IS-PCR is a powerful technique to detect viral DNA in human
      tissue sections, but requires proper use of negative controls to set optimal
      fixation, protein digestion, and amplification conditions.

PMID- 16437386
TI  - The transcription factor E2F: a crucial switch in the control of homeostasis and
      tumorigenesis.
AB  - The transcription factor E2F plays a crucial role in governing cell proliferation
      through manipulation of the expression of many genes required for cell cycle
      progression. As studies are exploring in depth, E2F has grown into a multimember
      family and has been required for the regulation of a large number of genes
      involved in various cellular processes. The expanding E2F membership and
      biological function provide us some new insights relating to the evolution of
      E2F. One of them is to understand the exact mechanisms by which E2F executes in
      these different cellular processes during ontogenesis. This review summarizes
      recent advances in this field, with an emphasis on a notion that E2F acts as a
      molecular switch in the control of both normal cell and tumor development.

PMID- 16437387
TI  - Molecular roles of MAP kinases and FADD phosphorylation in prostate cancer.
AB  - Mitogen activated protein (MAP) kinases are well known serine threonine kinases
      that modulate gene expression, mitosis, cell proliferation and programmed cell
      death or 'apoptosis' in response to various stresses. Extracellular stress
      regulated kinase (ERK), c-jun NH2 terminal kinase and p38 are major members of
      the MAP kinases, and there is now a body of evidence of their involvement in
      genesis or sensitivity to chemotherapy of human prostate cancers. In this review,
      we focus on the molecular roles of MAP kinases and their pathological
      correlations, with particular attention to novel downstream signals through
      phosphorylation of the Fas-associated death domain protein that effectively
      regulates not only apoptosis but also the cell cycle in prostate neoplastic
      cells.

PMID- 16437388
TI  - Cell cycle alterations and lung cancer.
AB  - It is now widely accepted that human carcinogenesis is a multi-step process and
      phenotypic changes during cancer progression reflect the sequential accumulation
      of genetic alterations in cells. The recent progress of scientific research has
      notably increased knowledge about biological events involved in lung cancer
      pathogenesis and progression, thanks to the use of molecular biology and
      immunohistochemistry techniques. Lots of the genetic alteration found in small
      cells lung cancer (SCLC) and in not small cells lung cancer (NSCLC) concern the
      expression of cell cycle genes, actually recognized as onco-suppressor genes and
      the lack of equilibrium between oncogenes and oncosuppressor genes. The present
      review of literature widely describes the cell cycle control, the lung cancer
      molecular pathogenesis, the catalog of known genetic alterations and the recent
      advances in global expression profiles in lung tumors, on the basis of the
      various hystological types too. Such data suggest the potential use of this
      knowledges in clinical practice both as prognostic factors and innovative
      therapeutic possibilities and they impose the necessity of new studies about cell
      cycle control and lung carcinogenesis.

PMID- 16437389
TI  - Genetic alterations and histopathologic findings in familial renal cell
      carcinoma.
AB  - Renal cell carcinoma is increasing in frequency in the United States and is often
      detected late in the course of disease due to nonspecific symptoms. A subset of
      renal cell carcinoma is attributable to familial or hereditary syndromes,
      including von Hippel-Lindau and Birt-Hogg-Dube syndromes, among others.
      Understanding of the molecular alterations in patients with familial syndromes
      may provide some insight into the underlying mechanisms of disease initiation and
      progression. This review describes the various subtypes of renal cell carcinoma
      and the familial syndromes associated with these tumors.

PMID- 16437390
TI  - Nitric oxide, a biological double-faced janus--is this good or bad?
AB  - Nitric oxide (NO) is a biological messenger molecule produced by one of the
      essential amino acids L-arginine by the catalytic action of the enzyme NO
      synthase (NOS). The dual role of NO as a protective or toxic molecule is due to
      several factors, such as; the isoform of NOS involved, concentration of NO and
      the type of cells in which it is synthesised, the availability of the substrate L
      arginine, generation of guanosine 3,5'-cyclic monophosphate (cGMP) from soluble
      guanylate cyclase and the overall extra and intracellular environment in which NO
      is produced. NOS activation as a result of trauma (calcium influx) or infection
      leads to NO production, which activates its downstream receptor sGC to synthesise
      cGMP and/or leads to protein nitrosylation. This may lead to one or more systemic
      effects including altered neurotransmission which can be protective or toxic,
      vaso/bronchodilatation in the cardiovascular and respiratory systems and enhanced
      immune activity against invading pathogens. In addition to these major functions,
      NO plays important role in thermoregulation, renal function, gastrointestinal
      motility, endocrine function, and various functions of the urogenital system
      ranging from renin secretion to micturation; spermatogenesis to penile erection;
      and ovulation to implantation and parturition. A schematic summary of the
      functions of NO and the various isoforms of NOS expressed in body systems is
      shown in figure 1. In this review, the historical background, biochemistry and
      biosynthesis of NO and its enzymes together with the mechanism of NO actions in
      physiology and pathophysiology are discussed.

PMID- 16437391
TI  - Image fusion in cardiology.

PMID- 16437392
TI  - Combination of physical exercise and adenosine improves accuracy of automatic
      calculation of stress LVEF in gated SPECT using QGS software.
AB  - BACKGROUND: Combining exercise and adenosine during the stress phase of
      myocardial perfusion imaging (MPI) is known to reduce adverse effects and improve
      image quality. The aim of this study was to assess whether it can also improve
      the automatic calculation of left ventricular ejection fraction (LVEF) by QGS
      software package, during the stress phase of Gated SPECT. MATERIAL AND METHODS:
      One hundred patients who had stress Gated SPECT were retrospectively included in
      this study. Gated data of those who had adenosine only (50 patients=group A) was
      compared with those obtained in another group of 50 patients who had added
      bicycle exercise (Group B). All had identical image acquisition protocol using
      (99m)Tc-tetrofosmine. Clinical adverse effects, changes in blood pressure (BP),
      heart rate (HR), and ECG were monitored. Visual assessment of subdiaphragmatic
      uptake and accuracy of automatic regions of interest (ROI's) drawn by the
      software were noted. Regions of interest that involved sub-diaphragmatic uptake
      and resulting in low LVEF were manually adjusted to include the left ventricle
      only, and the frequency of manual adjustment was noted. RESULTS: No significant
      difference was noted in age, sex, baseline BP and HR between groups A and B.
      Adverse effects occurred less often in group B compared to group A (12% vs. 24%,
      p=0.118). Maximum HR and BP achieved during stress were significantly higher in
      group B compared to group A (p=0.025, p=0.001 respectively). The number of
      patients who had faulty ROI's and low LVEF, who needed manual adjustment of
      ROI's, were higher in group A compared to group B (16% vs. 6%, p=0.025). The
      values of LVEF showed significant improvement following manual adjustment of
      ROI's, increasing from a mean of 19.63+/-15.96 to 62.13+/-7.55 (p=0.0001) and
      from 17.33+/-9.5 to 49.67+/- 7.7 (p=0.0014) in groups A and B respectively.
      CONCLUSION: The addition of exercise to adenosine significantly improves the
      automatic calculation of LVEF by QGS software during Gated SPECT and reduces the
      need for manual adjustment.

PMID- 16437393
TI  - Recurrent cerebral gliomas in MRI and Iodine-123[corrected]-alpha-methyl-tyrosine
      SPECT: the use of digitally fused images.
AB  - BACKGROUND: Early detection and site location of recurrent cerebral glioma helps
      design optimum therapeutic regimen, which contributes to prolonged survival time
      of the patients. However, diagnosing the neoplastic growth at the post-resection
      site is a difficult process. The diagnostic modality to provide the most
      extensive morphological data is dynamic MR tomography. On the other hand, the
      tumour-related metabolic changes can be best diagnosed using the PET and SPECT
      techniques of nuclear medicine that employ radiolabelled amino acid 131 I-alpha
      metyl-tyrosine (IMT) as the tracer. Thus, for comprehensive diagnostics of brain
      tumours, it is most effective to combine both the modalities and evaluate the
      fused images. The aim of the present study was to verify the usefulness of the
      calculated algorithm for a digital fusion of RM/SPECT images for the assessment
      of post-resection site of cerebral gliomas. MATERIAL AND METHODS: The findings of
      MR and SPECT imaging for 21 patients who had surgery for cerebral glioma were
      subject to assessment. Diagnosis was based on histopathology results (8 cases of
      anaplastic astrocytoma and 13 cases of multiform glioblastoma). The site and size
      of the contrast enhancement areas from MR was compared with the hot focus
      location from SPECT. RESULTS: The study confirmed the feasibility of digital
      fusion of images yielded by SPECT and MR. The fused images reflect the non
      homogeneity of the post-resection site of cerebral gliomas. Contrast enhancement
      areas only partially overlapped with the hot foci which, furthermore, were found
      to be substantially smaller. CONCLUSIONS: The consistency of tumour locations
      detected with MR and SPECT was higher for tumours of the anaplastic astrocytoma
      type than for multiform glioblastomas (higher polymorphism of pathological
      changes).

PMID- 16437394
TI  - Bone turnover markers and bone scintigraphy in the evaluation of the skeletal
      metastases.
AB  - BACKGROUND: The aim of this study was evaluation of the clinical usefulness of
      bone scintigraphy and of serum bone turnover marker levels in the assessment of
      skeletal metastases. MATERIAL AND METHODS: We investigated 60 patients with
      suspected skeletal metastases. Serum level of bone-formation marker: amino
      terminal propeptide of type I procollagen (PINP) and a bone-degradation marker:
      carboxy-terminal telopeptide of type I collagen (ICTP) were assessed with
      radioimmunoassays. Bone MDP-99m-Tc scans were performed as well. RESULTS: Hot
      spots were showed in 72% of patients. According to bone scintigraphy the patients
      were divided in to 3 groups: Group I - without hot spots (n=16; 26%), Group II up
      to 10 hot spots (n=25; 42%) and Group III more that 10 hot spots (n=19; 32%).
      Mean serum level of ICTP was significantly higher in Group II than in Group I (p<
      0.05), as well as in Group III compared to Group II (p< 0.001) and in Group III
      compared to Group I (p< 0.001). There is only one significant relationship in
      PINP levels - between Groups II and III. CONCLUSIONS: The levels of bone
      pathological degradation (ICTP) and bone formation reflect the metastatic disease
      extent in bone. Serum ICTP level is more useful in staging metastasis.
      Significantly higher PINP reflects only a much disseminated process.

PMID- 16437395
TI  - Evaluation of surgical gamma probes for sentinel node localization in cervical
      and vulvar cancer.
AB  - BACKGROUND: Sentinel node (SN) scintigraphy for cervical and vulvar cancer guides
      the gynaecological oncologist in finding the metastatic lymph nodes during
      lymphadenectomy. The role of the surgical gamma probe in the sentinel node
      concept in gynaecological oncology is to localise (SN) both intra-operatively and
      transcutaneously. Intra-operative hand-held collimated gamma probes are
      increasingly used for detection of the sentinel lymph node. MATERIAL AND METHODS:
      A comparative evaluation of hand held gamma probes: Neoprobe 1,500, Europrobe,
      Gamma Finder, Gamma Ray Prospector GRP1 and GPR2 was performed using different
      detection methods. Laboratory tests were performed in which sensitivity, spatial
      resolution and angular sensitivity were evaluated. RESULTS: The results for each
      gamma probe were summarised and discussed. CONCLUSION: Awareness of a gamma
      probeis capabilities and limitations should be considered in the appropriate
      selection of a device.

PMID- 16437396
TI  - Additional value of hybrid PET/CT fusion imaging vs. conventional CT scan alone
      in the staging and management of patients with malignant pleural mesothelioma.
AB  - BACKGROUND: Despite being a relatively rare disease, the incidence of malignant
      pleural mesothelioma (MPM) is expected to increase over the next two decades due
      to the long time interval elapsing between exposure to causative factors, mainly
      asbestos, and disease onset. Early disease stages have been reported to benefit
      from radical surgery. In more advanced disease stages, a multimodality treatment,
      including various combinations of chemotherapy, external radiotherapy and
      surgery, may provide some favourable results though the prognosis remains poor.
      In this regard, an accurate pre-treatment staging plays an important role in
      offering patients a more appropriate therapeutic planning. In some preliminary
      studies, (18)F-FDG PET has proven to be able to provide useful information for
      staging purpose, especially for the detection of metastatic spread to lymph nodes
      and distant sites. MATERIAL AND METHODS: In the present study, we investigated 15
      consecutive patients with histologically proven MPM by means of conventional 2-mm
      thickness whole-body CT scan with and without contrast medium in comparison with
      wholebody (18)F-FDG PET/CT fusion imaging. RESULTS: (18)F-FDG PET/CT did not
      provide additional information about the primary tumour (T) compared to CT scan,
      but identified a higher number of metastatic mediastinal lymph nodes (N) in 6
      patients (40% of cases) and unknown metastatic disease to distant sites (M) in 3
      patients (20% of cases). On the basis of PET/CT findings, treatment planning was
      changed in 5 patients (33.3% of cases). CONCLUSIONS: Our data show that (18)F-FDG
      PET/CT fusion imaging can play a relevant role in the staging and treatment
      planning of MPM patients.

PMID- 16437397
TI  - Uncertainty analysis of (99m)Tc-HEPIDA liver clearance determination.
AB  - BACKGROUND: The aim of the study was to obtain information on the accuracy and
      precision of (99m)Tc-HEPIDA hepatic (Cl(Hp)) and plasma (Cl(Pl)) clearances and
      selection of an appropriate estimator of the measurement uncertainty of a single
      determination of these quantities. MATERIAL AND METHODS: In a simulation (Monte
      Carlo) experiment, it was assumed that the recorded results of plasma and hepatic
      clearances, as obtained from 185 patients, provided authentic information about
      (99m)Tc-HEPIDA behaviour in the body over a wide range of the clearances studied.
      The time course (99m)Tc-HEPIDA concentration in blood plasma has been described
      by means of biexponential function with parameter values derived for each
      patient. For each patient, using these data and urinary excretion data, there had
      been 5000 simulations performed; in each of the latter, the directly measured
      numbers have been substituted by simulated ones, obtained by means of varying the
      real ones, using random generated values. These reflected errors of plasma and
      radioactive standard pipetting (from 1 to 5%) and stochasticity of counting
      radioactive decay (1%). The time of blood sampling and urine voiding was also
      varied, assuming realistic uncertainty. The varied values were then used for
      computation of the simulated clearances. From the 5,000 calculated clearances for
      each patient, mean-values were calculated, as well as mean standard errors,
      standard deviations and mean uncertainty of measurements using a widely accepted
      rule of partial error propagation, and, in addition, a modified rule of the
      latter. Accuracy of clearance (Cl(Pl), Cl(Hp), Cl(Ur)) determination was assessed
      on the basis of comparison of mean values from simulations with those from
      directly recorded values. Precision was identified with standard deviation of
      each of the 5000 simulations. The uncertainty thus obtained was compared with
      results of calculated traditional and modified uncertainty. There was good
      agreement between standard deviation of the simulations with results of the
      modified calculation of total differential. Therefore, a coefficient of variation
      from simulation computations and a modified means of calculation of the
      propagated errors was accepted as a measure of uncertainty of a single
      determination. RESULTS/CONCLUSIONS: There was a very high correlation between the
      mean values from simulations and those from direct determinations (r > 0.98 in
      each case). The regression lines practically corresponded to the lines of
      identity. These correlations were not affected by the assumed range of pipetting
      uncertainty. In conclusion, the methods of (99m)Tc-HEPIDA clearance determination
      are satisfactory. Precision of clearance measurements depends substantially upon
      uncertainty of pipetting. For plasma clearance, the coefficients of variations at
      Cl(Pl) > 350 ml/min and at ab.80 ml/min amounted to 2 and 11% respectively, at
      pipetting uncertainty of 2%. Similarly, for hepatic clearances of (99m)Tc-HEPIDA
      of 300 ml/min and 30 ml/min, CV was 2.5 and 25%, respectively (at the same
      uncertainty of pipetting).

PMID- 16437398
TI  - Skin eruptions following treatment with Iodine-131 for hyperthyroidism: a rare
      and un-reported early/intermediate side effect.
AB  - BACKGROUND: Iodine-131 ((131)I) is a well-established method for the treatment of
      hyperthyroidism. Following such therapy, patients may experience symptoms
      relating to early or delayed side effects that can be prevented or minimized if
      necessary measures are taken. We have noticed an unusual side effect of (131)I
      therapy in the form of a skin eruption (iododerma) and aimed at assessing the
      frequency and severity of this side effect. MATERIAL AND METHODS: Retrospective
      review of 141 patients treated with (131)I between January 1994 to December 2000
      (86 F, 55 M; mean age 41.35 +/- 11.02 years) was performed. The dose of (131)I
      ranged from 250-500 MBq. Post therapy clinical and biochemical evaluation of
      thyroid function was done at 6 weeks, 3, 6, and 9 months then annually. RESULTS:
      Of the 141 treated patients, 3 patients (2.1%) presented with iododerma 4-6 weeks
      after (131)I therapy administration. Lesions were observed at both ankles & lower
      legs in all 3 cases. All lesions disappeared within 6 months with no residual
      effect. No other skin lesions were seen thereafter during the follow-up period.
      CONCLUSION: Iododerma is a rare complication of (131)I therapy that has not been
      reported before. It appears within 4-6 weeks after therapy and is a self-limiting
      condition.

PMID- 16437399
TI  - Evaluation of sentinel node detection in vulvar cancer.
AB  - BACKGROUND: In vulvar cancer, in a large portion of patients with early stages of
      the disease, the inguinal lymphadenectomy not only does not influence the overall
      survival and recurrence rate but may increase the incidence of complications.
      Sentinel lymph node (SN) detection is a promising technique for detecting groin
      lymph nodes, which may in future lead to less extensive use of surgical
      treatment. The aim of the study was to evaluate the feasibility of the sentinel
      node detection technique in patients with vulvar cancer. MATERIAL AND METHODS:
      Between the years 2003 and 2005, we performed intraoperative lymphatic mapping on
      10 patients with planoepithelial vulvar cancer. In eight cases, vulvar lesion was
      localized centrally, around the clitoris. The extent of the surgery included
      radical vulvectomy with bilateral inguinal lymphadenectomy in nine cases and
      unilateral inguinal lymphadenectomy in one case. For the lymphatic mapping, we
      employed two detection methods: (99m)Tc-labelled radiocolloid (activity 35-70
      MBq) and blue dye (3-5 ml). Both techniques were used in six cases (60%), blue
      dye only in three cases and radiocolloid only in one case. RESULTS: In each
      patient, we detected at least one sentinel lymph node. Sentinel nodes were
      localized in 14 of 19 operated groins (73.7%); a total of 25 SNs in all. The mean
      number of SNs for one groin was 1.78. Nodal metastases were found in four cases.
      In three cases, metastases were detected only in the SN. In one patient, two SNs
      with metastases were found in one groin and in the contralateral groin (without
      any SN) there was one unchanged node, which transpired to be metastatic. This can
      be explained by a complete overgrowth of neoplasm in the lymph node resulting in
      lymph flow stasis and disabling tracer uptake. In five cases, an SN was found
      only in one groin o the first case is described above, in the second case the
      vulvar tumor was localized laterally, opposite to the groin without any SN. In
      the remaining three cases, we have used only one method of SN detection.
      CONCLUSIONS: Lymphatic mapping in vulvar cancer based on the combined detection
      technique is a highly accurate method after adequate training of the surgeons.

PMID- 16437400
TI  - Our first clinical experience with radiosynoviorthesis by means of (166)Ho
      holmium-boro-macroaggregates.
AB  - BACKGROUND: In this paper, we evaluate the therapeutic and adverse effects of the
      application of 166-holmium-boro-macroaggregates (HMBA) in radiosynovectomy (RSO)
      of the knees. We assessed the efficacy and safety of (166)Ho-HBMA in a
      prospective clinical trial in patients suffering from chronic synovitis. MATERIAL
      AND METHODS: An effective component of radiopharmaceutical (166)Ho-boro
      macroaggregates is radionuclide (166)Ho which has both beta-emission and gamma
      emission. The physical half-life time of 166 Ho is 26.8 hours. After application
      of the radiopharmaceutical into a joint cavity, the effect of beta-emission
      causes radiation necrosis of pathologically changed (inflamed) synovial membrane.
      From 15th April 2005, we have started RSO of knees by means of new
      radiopharmaceutical (166)Ho-boro-macroaggregates in patients with gonarthrosis,
      rheumatoid arthritis, chronic synovitis, psoriatic arthritis, gout arthropathy.
      Seventeen intra-articular injections were performed in fifteen patients receiving
      a mean activity of 972 MBq (range: 904-1,057 MBq) (166)Ho-HMBA. The patients were
      hospitalized for three days. Side effects were evaluated during hospital stay and
      after 6-8 weeks. Static scintigraphy of knee joints and measurements of blood
      radioactivity were performed. Therapeutic effects were evaluated after 6-8 weeks.
      RESULTS: In 2 hours and 2 days after application, we proved, by means of knee and
      inguinal scintigraphy, only insignificant radiopharmaceutical leakage from the
      joint cavity to the inguinal lymph nodes in four patients. In treated patients,
      no serious adverse effects occurred. Nine patients were without complaints; 4
      patients had slight knee exsudation and 2 patients had great exsudation.
      Therapeutic effects after 6-8 weeks were as follows: 2 patients were without
      pain, 9 with lower pain, 3 with the same pain and 1 patient with increased pain.
      Joint motion was improved in 7 patients, remained the same in 7 patients and was
      impaired in 1 patient. Analgesics consumption was lower in 5 patients, the same
      in 9 patients and greater in 1 patient. Knee exsudation was absent in 2 patients,
      lower in 4 patients, the same in 6 patients and greater in 3 patients.
      CONCLUSIONS: We proved only insignificant radiopharmaceutical leakage from the
      joint cavity to the inguinal lymph nodes. Six patients had early slight or great
      radiation synovitis. The possible cause could be rather high applicated activity.
      One can take into consideration its reduction. Therapeutic effects can be
      precisely evaluated after a longer time interval than was possible for us (6-8
      weeks after RSO). (166)Ho-boro-macroaggregates can extend the scale of clinically
      used radiopharmaceuticals for RSO. This paper is presented in the scope of the
      first stage of clinical evaluation of synovectomy application of holmium-boro
      macroaggregates.

PMID- 16437401
TI  - FDG-PET imaging in Merkel cell carcinoma - value of head-to-toe scan.
AB  - A 63-year-old man was diagnosed with metastatic MCC. Preliminary staging PET scan
      with 18F-FDG was not done at the time of diagnosis. After completion of chemo-
      and radiotherapy, the patient underwent a CT scan of the area from the maxilla to
      the ischium; no evidence of disease was noted. Clinically, the patient was
      considered to be in remission. The CT scan was followed by head-to-toe FDG-PET
      scanning which revealed foci of metastatic disease in the right mid- thigh and
      left proximal calf. This case demonstrates the added value of head-to-toe FDG-PET
      for the detection of distant metastases in MCC.

PMID- 16437402
TI  - The case of Cushing's disease imaging by SPECT examination without manifestation
      of pituitary adenoma in MRI examination.
AB  - BACKGROUND: The aim of our study was to evaluate the possibility of imaging the
      pathological accumulation of (99m)Tc-MIBI in the pituitary gland in patients with
      Cushing's disease when MRI examination does not show microadenomas. MATERIAL AND
      METHODS: Cushing's disease was diagnosed in a 27 year old male on the basis of
      clinical and biochemical findings. The blood cortisol level of the patient was
      elevated (the average level was 47 ug/dl) and it showed no changeability of day
      and night rhythm. RESULTS: In the patient with Cushing's disease, during the
      SPECT examination, an increased accumulation of (99m)Tc-MIBI in the pituitary
      gland was noticed. MRI scanning was negative. CONCLUSION: Single photon emission
      computed tomography using (99m)Tc-MIBI is a useful and sensitive means of
      pituitary gland microadenoma detection in patients with Cushing's disease when
      microadenoma is not detected during MRI scanning and when the results of
      dexamethasone suppression test is positive.

PMID- 16437403
TI  - Optimisation of statistical methodologies for a better diagnosis of neurological
      and psychiatric disorders by means of SPECT.
AB  - In the last years there has been a wide consensus on the importance of brain
      imaging in assessing neurodegenerative and psychiatric disorders. Different
      techniques for functional and anatomical examination are currently clinically
      implemented in neurology and psychiatry to improve sensitivity, specificity and
      accuracy of the diagnosis of various diseases. In addition, the increasing life
      expectancy in the Western world raises the social importance and the economical
      impact of age-related neurodegenerative disorders since the incidence of
      Alzheimer disease and Parkinson disease is higher in the elderly. An early
      diagnosis of neuro-psychiatric diseases and the assessment of "natural" changes
      of regional cerebral blood flow (rCBF) distribution during normal aging are hence
      of utmost importance. In the recent past brain disorders have extensively been
      investigated by means of optimised nuclear medicine techniques, instruments and
      algorithms. Diagnosis can be better achieved by identifying those structures in
      which CBF or metabolism deviate from normality resulting in significant changes
      as compared to a reference database. In the present paper we present some studies
      investigating, by means of recently implemented diagnostic tools, patients bearer
      of various neuro-psychiatric disorders. The improved nuclear medicine techniques
      and instrumentation, the state-of-the-art software for brain imaging
      standardisation and the use of sophisticated multivariate data analysis are
      extensively reviewed.

PMID- 16437404
TI  - Usefulness of (99m)Tc(V)-dimercaptosuccinic acid scintigraphy in the assessment
      of response to external radiation therapy in soft tissue sarcoma in Giant Snauzer
      dog.
AB  - A nine-year-old male black Giant Schnauzer dog was referred for the scintigraphic
      evaluation with a history of malignant fibrosarcoma with a rapidly growing non
      painful mass on the left shoulder region quite near to the site of an operation
      performed four months ago. We carried out oncological scintigraphy using
      pentavalent (99m)Technetium labelled dimercaptosuccinic acid [(99m)Tc(V)-DMSA], a
      tumour localising radiopharmaceutical agent. The study was performed to assess
      the margins, vascularity of the tumour and response to the cancer therapy.
      Uniform intense radiopharmaceutical uptake was observed in the lesion indicating
      its margins, vascularity and malignant nature. The dog was subjected to external
      radiation therapy to control the growth of the cancer and to bring the tumour
      mass to an operable size. The dog was followed up with (99m)Tc(V)-DMSA
      scintigraphy pre-irradiation and post-irradiation. Immediately after the post
      irradiation scintigraphy, the dog was operated on. During the surgery, resection
      of the tumour margins was performed carefully using a hand held gamma probe to
      assure that no tumour tissue was left inside. In conclusion, the authors would
      like to state that (99m)Tc(V)-DMSA oncoscintigraphy is valuable in the assessment
      and evaluation of therapy in canine soft tissue cancer.

PMID- 16437405
TI  - Increased uptake of technetium-99m methylene diphosphonate in muscles in the
      course of polymyositis.
AB  - A case of a woman aged 46 years with signs of rhabdomyolysis and acute renal
      failure is presented. Coxsackie serum test was positive. Increased uptake of
      Technetium-99m methylene diphosphonate (99mTc-MDP) by muscles of thighs and
      calves was observed. After 1 year no increased accumulation of radiotracer in the
      muscles was found.

PMID- 16437406
TI  - (99m)Tc-EDDA/HYNIC-octreotate - a new radiotracer for detection and staging of
      NET: a case of metastatic duodenal carcinoid.
AB  - Somatostatin receptor scintigraphy (SRS) has become a routine imaging method for
      the diagnostics of neuroendocrine tumours (NET). (99m)Tc-EDDA/HYNIC-octreotate
      (Polatom, Poland) is a new radiotracer with high affinity for SSTR2 and similar
      physiological biodistribution to (111)In-Octreoscan. We present a case of a 47
      year-old man with disseminated duodenal carcinoid. The patient had been operated
      due to the tumour mass detected in pancreatic head area. Histopathology revealed
      carcinoid of the duodenal wall with local lymph node and liver metastases. The
      patient was qualified for chemotherapy stopped due to severe leucopenia. (99m)Tc
      EDDA/HYNIC-octreotate scintigraphy was performed for staging and to determine
      SSTR status of the tumour before planned 90Y-DOTATATE therapy. The multiple
      metastatic lesions were detected all over the body. The high quality images with
      high target/non target ratio were obtained. (99m)Tc-MDP scintigraphy confirmed
      multiple bone metastases. On the basis of SRS result the patient was qualified
      for 90Y-DOTA-TATE therapy. In conclusion, (99m)Tc EDDA/HYNIC-octreotate can be
      regarded as a promising tracer for staging and to determine SSTR status of NET.

PMID- 16437407
TI  - Does the Luxembourgish Society of Nuclear Medicine (SLMN) really exist?

PMID- 16437408
TI  - PET Center - Masaryk Memorial Cancer Institute, Brno, Czech Republic.

PMID- 16437410
TI  - Chosen abstracts of Czech Society of nuclear Medicine Congress, Liberec 2005.

PMID- 16437418
TI  - Unknown biological mixtures evaluation using STR analytical quantification.
AB  - Allelic quantification of STRs, where the presence of three or more alleles
      represents mixtures, provides a novel method to identify mixtures from unknown
      biological sources. The allelic stutters resulting in slightly different repeat
      containing products during fragment amplification can be mistaken for true
      alleles complicating a simple approach to mixture analysis. An algorithm based on
      the array of estimated stutters from known samples was developed and tuned to
      maximize the identification of true non-mixtures through the analysis of three
      pentanucleotide STRs. Laboratory simulated scenarios of needle sharing generated
      58 mixture and 38 non-mixture samples that were blinded for determining the
      number of alleles. Through developing and applying an algorithm that additively
      estimates stuttering around the two highest peaks, mixtures and non-mixtures were
      characterized with sensitivity of 77.5, 82.7 and 58% while maintaining the high
      specificity of 100, 97.4 and 100 for the W, X, and Z STRs individually. When all
      three STRs were used collectively, the resulting sensitivity and specificity was
      91.4 and 97.4%, respectively. The newly validated approach of using multiple STRs
      as highly informative biomarkers in unknown sample mixture analyses has potential
      applications in genetics, forensic science, and epidemiological studies.

PMID- 16437419
TI  - Protective effect of caffeic acid phenethyl ester (CAPE) administration on
      cisplatin-induced oxidative damage to liver in rat.
AB  - Cisplatin is one of the most active cytotoxic agents in the treatment of cancer.
      High doses of cisplatin have also been known to produce hepatotoxicity. Several
      studies suggest that supplementation with an antioxidant can influence cisplatin
      induced hepatotoxicity. The present study was designed to determine the effects
      of cisplatin on the liver oxidant/antioxidant system, and the possible protective
      effects of caffeic acid phenethyl ester (CAPE) on liver toxicity induced by
      cisplatin. Twenty-four adult female Wistar albino rats were divided into four
      groups of six rats each: control, cisplatin, CAPE, and cisplatin+CAPE. Cisplatin
      and CAPE were injected intraperitoneally. Liver tissue was removed to study the
      activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase
      (GSH-Px), myeloperoxidase (MPO), xanthine oxidase (XO), adenosine deaminase
      (ADA), and the levels of malondialdehyde and nitric oxide (NO). The activities of
      SOD and GSH-Px increased in the cisplatin+CAPE and CAPE groups compared with the
      cisplatin group. CAT activity was higher in the cisplatin +CAPE group than the
      other three groups. XO activity was lower in the cisplatin group than the control
      group. MPO activity was also increased in the cisplatin group compared to the
      control and CAPE groups. It can be concluded that CAPE may prevent cisplatin
      induced oxidative changes in liver by strengthening the antioxidant defence
      system by reducing reactive oxygen species and increasing antioxidant enzyme
      activities.

PMID- 16437420
TI  - Acupuncture and related interventions for smoking cessation.
AB  - BACKGROUND: Acupuncture and related techniques are promoted as a treatment for
      smoking cessation in the belief that they may reduce nicotine withdrawal
      symptoms. OBJECTIVES: The objectives of this review are to determine the
      effectiveness of acupuncture and the related interventions of acupressure, laser
      therapy and electrostimulation, in smoking cessation in comparison with no
      intervention, sham treatment, or other interventions. SEARCH STRATEGY: We
      searched the Cochrane Tobacco Addiction Group specialized register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, BIOSIS
      Previews, PsycINFO, Science and Social Sciences Citation Index, AMED and CISCOM.
      Date of last search January 2005. SELECTION CRITERIA: Randomized trials comparing
      a form of acupuncture, acupressure, laser therapy or electrostimulation with
      either no intervention, sham treatment or another intervention for smoking
      cessation. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the
      type of smokers recruited, the nature of the acupuncture and control procedures,
      the outcome measures, method of randomization, and completeness of follow up. We
      assessed abstinence from smoking at the earliest time-point (before six weeks),
      and at the last measurement point between six months and one year. We used the
      most rigorous definition of abstinence for each trial, and biochemically
      validated rates if available. Those lost to follow up were counted as continuing
      smokers. Where appropriate, we performed meta-analysis using a fixed-effect
      model. MAIN RESULTS: We identified 24 reports of studies. The only comparison for
      which there were sufficient studies to combine meaningfully was acupuncture
      compared with sham acupuncture. The fixed-effect odds ratio (OR) for the short
      term effect was 1.36 (95% confidence interval 1.07 to 1.72), but the studies are
      heterogeneous and the result is strongly influenced by one individual positive
      study. The significant short-term effect was lost with the random-effects model
      for pooling, or by removing the outlying study that led to heterogeneity. The
      long-term result shows no effect of acupuncture compared with sham acupuncture.
      There was no consistent evidence that acupuncture is superior to no treatment,
      and no evidence that the effect of acupuncture was different from that of other
      anti-smoking interventions, or that any particular acupuncture technique is
      superior to other techniques. AUTHORS' CONCLUSIONS: There is no consistent
      evidence that acupuncture, acupressure, laser therapy or electrostimulation are
      effective for smoking cessation, but methodological problems mean that no firm
      conclusions can be drawn. Further research using frequent or continuous
      stimulation is justified.

PMID- 16437421
TI  - External cephalic version for breech presentation before term.
AB  - BACKGROUND: External cephalic version (ECV) of the breech fetus at term (after 37
      weeks) has been shown to be effective in reducing the number of breech
      presentations and caesarean sections, but the rates of success are relatively
      low. This review examines studies initiating ECV prior to term (before 37 weeks'
      gestation). OBJECTIVES: To assess the effectiveness of a policy of beginning ECV
      before term (before 37 weeks' gestation) for breech presentation on fetal
      presentation at birth, method of delivery, and the rate of preterm birth,
      perinatal morbidity, stillbirth or neonatal mortality. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group Trials Register (April
      2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library,
      Issue 1, 2005), MEDLINE (1965 to April 2005), EMBASE (1988 to April 2005), and
      Controlled Clinical Trials randomised controlled trials registry (April 2005).
      SELECTION CRITERIA: Randomised trials of ECV beginning before term (before 37
      weeks' gestation) compared with a control group in women with breech presentation
      before term. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed eligibility and trial quality and extracted data. MAIN RESULTS: Three
      studies are included. One study reported on ECV that was undertaken and completed
      before 37 weeks' gestation compared to no ECV. No difference was found in the
      rate of non-cephalic presentation at birth. One study reported on a policy of ECV
      that was initiated before term (33 weeks) and up until 40 weeks' gestation and
      which could be repeated up until delivery compared to no ECV. This study showed a
      decrease in the rate of non-cephalic presentation at birth (relative risk 0.59,
      95% confidence interval 0.45 to 0.77). One study reported on ECV started at
      between 34 to 35 weeks' gestation compared to beginning at 37 to 38 weeks'
      gestation. Although findings were not statistically significant, a 9.5% decrease
      in the rate of non-cephalic presentation at birth and a 7% decrease in the
      caesarean section rate were reported when ECV was started early. AUTHORS'
      CONCLUSIONS: Compared with no ECV attempt, ECV commenced before term reduces non
      cephalic births. Compared with ECV at term, beginning ECV at between 34 to 35
      weeks may have some benefit in terms of decreasing the rate of non-cephalic
      presentation, and caesarean section. Further trials are needed to confirm this
      finding and to rule out increased rates of preterm birth, or other adverse
      perinatal outcomes. A large pragmatic trial is ongoing
      (www.utoronto.ca/miru/eecv2).

PMID- 16437422
TI  - Extramedullary fixation implants and external fixators for extracapsular hip
      fractures in adults.
AB  - BACKGROUND: Extramedullary fixation of hip fractures involves the application of
      a plate and screws to the lateral side of the proximal femur. In external
      fixators, the stabilising component is held outside the thigh by pins or screws
      driven into the bone. OBJECTIVES: To compare different types of extramedullary
      fixation implants and external fixators for fixing extracapsular hip fracture in
      adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma
      Group Specialised Register (July 2005), various other databases, conference
      proceedings and reference lists. SELECTION CRITERIA: All randomised or quasi
      randomised controlled trials comparing extramedullary implants or external
      fixators for fixing extracapsular hip fracture in adults. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected trials, assessed trial quality and
      extracted data. Data were pooled where appropriate. MAIN RESULTS: The 14 included
      trials tested seven comparisons in a total of 2222 mainly female and older
      participants. All trials had methodological flaws that may affect the validity of
      their results. Three trials comparing a fixed nail plate (Jewett or McLaughlin)
      with the sliding hip screw (SHS) found an increased risk of fixation failure for
      fixed nail plates. The two trials comparing the Resistance Augmented Bateaux
      (RAB) plate with the SHS had contrasting results, notably in terms of operative
      complications, fixation failure and anatomical restoration. One trial comparing
      the Pugh nail and the SHS found no significant difference between implants. Two
      trials compared the Medoff plate with the SHS. One trial reported higher blood
      losses and longer operation times for the Medoff plate. There was a lower risk of
      fixation failure with the Medoff plate for unstable trochanteric fractures. Two
      trials compared the Medoff plate with three different screw-plate systems. There
      were no statistically significant differences in outcome for trochanteric
      fractures. For subtrochanteric fractures, there was a lower fixation failure rate
      for the Medoff plate, but no evidence for differences in longer-term outcomes.
      Two trials comparing the Gotfried percutaneous plate with a SHS found a reduced
      blood loss with the Gotfried plate. A higher intra-operative fixation failure
      rate of the Gotfried plate may indicate some restriction to its use. Two trials
      found less operative trauma for external fixation when compared with the SHS.
      Final outcome appeared similar. AUTHORS' CONCLUSIONS: The markedly increased
      fixation failure rate of fixed nail plates compared with the SHS is a major
      consideration and thus the SHS appears preferable. There was insufficient
      evidence from other comparisons to draw definite conclusions.

PMID- 16437423
TI  - Rescue high frequency jet ventilation versus conventional ventilation for severe
      pulmonary dysfunction in preterm infants.
AB  - BACKGROUND: Chronic pulmonary disease is a major cause of mortality and morbidity
      in very low birth weight infants despite increased use of antenatal steroids and
      surfactant therapy. Ventilator injury and oxygen toxicity are thought to be
      important factors in the pathogenesis of chronic pulmonary disease. There is
      evidence in animal studies and adult human studies that high frequency jet
      ventilation may reduce the severity of lung injury associated with mechanical
      ventilation. OBJECTIVES: In preterm infants with severe pulmonary dysfunction,
      does the use of high frequency jet ventilation (HFJV) compared to conventional
      ventilation (CV) reduce mortality and morbidity without an increase in adverse
      effects? SEARCH STRATEGY: We searched MEDLINE (1966 - August 2005), Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3,
      2005), and EMBASE (1988 - August 2005). Information was also obtained from
      experts in the field and cross references were checked. SELECTION CRITERIA:
      Randomized and quasi-randomized controlled trials of rescue high frequency jet
      ventilation versus conventional ventilation in preterm infants born at less than
      35 weeks of gestation or with a birth weight less than 2000 grams with
      respiratory distress were included in the systematic review. DATA COLLECTION AND
      ANALYSIS: The standard methods of the Cochrane Neonatal Review Group were used,
      including independent trial assessment and data extraction. Data were analysed
      using relative risk (RR) and risk difference (RD). MAIN RESULTS: Two randomized
      trials were identified. One trial (Engle 1997) was excluded as the study was
      restricted to term and near-term infants. The included trial (Keszler 1991)
      randomized 166 preterm infants and reported data on 144 infants. Cross-over to
      the alternate treatment was permitted if the initial treatment failed. There was
      no statistically significant difference in the overall mortality (including
      survival after cross-over) between the two groups [RR 1.07, (95% CI 0.67, 1.72)].
      The survival by original assignment was identical. In a secondary analysis, the
      study demonstrated rescue treatment with HFJV, up until the time of cross-over,
      was associated with lower mortality, [RR 0.66 (95% CI 0.45,0.97)]. No significant
      differences were found in the incidence of CLD in survivors at 28 days of age,
      IVH, new air leaks, airway obstruction and necrotizing tracheobronchitis.
      AUTHORS' CONCLUSIONS: There was no significant difference in the overall
      mortality between rescue high frequency jet ventilation and conventional groups.
      In a secondary analysis, rescue treatment with HFJV, up until the time of cross
      over, was associated with lower mortality. There was no significant increase in
      adverse effects like intraventricular hemorrhage, new air leaks, airway
      obstruction and necrotizing tracheobronchitis with rescue high frequency jet
      ventilation. The included study was done before the introduction of surfactant
      and widespread use of antenatal steroids. The number of infants included was
      small and there were high numbers of post randomization exclusions. Due to the
      crossover design and small numbers of infants in the included study, there is
      insufficient information to assess the effectiveness of rescue HFJV in preterm
      infants. Studies that target the most at-risk population and have appropriate
      power to assess some of the important outcomes are needed. These trials would
      also need to incorporate long term pulmonary and neurodevelopmental outcomes.

PMID- 16437424
TI  - Non-neuroleptic catecholaminergic drugs for neuroleptic-induced tardive
      dyskinesia.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated
      with the prolonged use of neuroleptic medication. Several strategies have been
      examined in the treatment of TD. Currently, however, there is no clear evidence
      of the effectiveness of these drugs in TD and they have been associated with many
      side effects. One particular strategy would be to use pharmaceutical agents which
      are known to influence the catecholaminergic system at various junctures.
      OBJECTIVES: To determine whether catecholaminergic drugs for people with
      schizophrenia or other chronic mental illnesses are associated with a reduction
      in neuroleptic-induced tardive dyskinesia. SEARCH STRATEGY: We searched the
      Cochrane Schizophrenia Group's Register (January 1996), Biological Abstracts
      (1982-1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995) and
      PsycLIT (1974-1995). We searched the Cochrane Schizophrenia Group's Register
      again in December 2002 and September 2005. We also searched references of all
      relevant studies for further trial citations and contacted principal authors of
      trials. SELECTION CRITERIA: We selected studies if they were randomised
      controlled trials focusing on people with schizophrenia or other chronic mental
      illnesses who also suffered from neuroleptic-induced tardive dyskinesia. We
      compared the use of catecholaminergic interventions versus placebo or no
      intervention. DATA COLLECTION AND ANALYSIS: We independently extracted data. For
      homogenous dichotomous data, we calculated the random effects, relative risk
      (RR), and 95% confidence interval (CI) and, where appropriate, the numbers needed
      to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated
      weighted mean differences (WMD). MAIN RESULTS: We excluded 20 studies, mainly due
      to an inability to extract data from the first arm of the study crossover. One
      included study has shown that patients on placebo were no more likely to leave
      the study early than those on tiapride (n=24). The other included study (n=35)
      also reported equivocal data (RR 5.28 CI 0.3 to 102.6) for leaving the study
      early when participants were randomised to either celiprolol or placebo. However,
      in both studies, sample size was limited. AUTHORS' CONCLUSIONS: Although there
      has been a large amount of research in this area, most studies were excluded due
      to inherent problems in the nature of their crossover designs. Usually data are
      not reported before the crossover and the nature of TD and its likely response to
      treatments makes it imprudent to use this data. The review provides little usable
      information for service users or providers and more well designed and reported
      studies are indicated.

PMID- 16437425
TI  - Neuroleptic reduction and/or cessation and neuroleptics as specific treatments
      for tardive dyskinesia.
AB  - BACKGROUND: Since the 1950s neuroleptic medication has been extensively used to
      treat people with chronic mental illnesses such as schizophrenia. These drugs,
      however, have been also associated with a wide range of adverse effects,
      including movement disorders such as tardive dyskinesia (TD). Various strategies
      have been examined to reduce a person's cumulative exposure to neuroleptics.
      These studies include dose reduction, intermittent dosing strategies such as drug
      holidays, and neuroleptic cessation. OBJECTIVES: To determine whether a reduction
      or cessation of neuroleptic drugs is associated with a reduction in TD, for
      people with schizophrenia (or other chronic mental illnesses) who have existing
      TD. Our secondary objective was to determine whether the use of specific
      neuroleptics for similar groups of people could be a treatment for TD that was
      already established. SEARCH STRATEGY: We updated previous searches of the
      Cochrane Schizophrenia Groups Register (1997), Biological Abstracts (1982-1997),
      EMBASE (1980-1997), LILACS (1982-1996), MEDLINE (1966-1997), PsycLIT (1974-1997),
      and SCISEARCH (1997) by searching the Cochrane Schizophrenia Groups Register
      (July 2003). We searched references of all identified studies for further trial
      citations. We also contacted the principal authors of trials for further
      unpublished trials. SELECTION CRITERIA: We included reports if they assessed
      people with schizophrenia or other chronic mental illnesses who had established
      neuroleptic-induced TD, and had been randomly allocated to (a) neuroleptic
      maintenance versus neuroleptic cessation (placebo or no intervention), (b)
      neuroleptic maintenance versus neuroleptic reduction (including intermittent
      strategies), and (c) specific neuroleptics for the treatment of TD versus,
      placebo or intervention. A post hoc decision was made to broaden comparison (c)
      to include specific neuroleptics versus other neuroleptics for the treatment of
      TD. DATA COLLECTION AND ANALYSIS: We (KSW, JR) independently inspected citations
      and, where possible, abstracts, ordered papers, and re-inspected and quality
      assessed these and extracted data. We analysed dichotomous data using random
      effects relative risk (RR) and estimated the 95% confidence interval (CI). Where
      possible we calculated the number needed to treat (NNT) or number needed to harm
      statistic (NNH). We excluded continuous data if more than 50% of people were lost
      to follow up, but, where possible, we calculated the weighted mean difference
      (WMD). It was assumed that those leaving the study early showed no improvement.
      MAIN RESULTS: We included five trials and excluded 102. One small two week study
      (n=18), reported on the 'masking' effects of molindone and haloperidol on TD,
      which favoured haloperidol (RR 3.44 CI 1.1 to 5.8). Two (total n=17) studies
      found no reduction in TD associated with neuroleptic reduction (RR 0.38 CI 0.1 to
      1.0). One study (n=20) found no significant differences in oral dyskinesia (RR
      2.45 CI 0.3 to 19.7) when neuroleptics were compared as a specific treatment for
      TD. Dyskinesia was found to be not significantly different (n=32, RR 0.62 CI 0.3
      to 1.26) between quetiapine and haloperidol when these neuroleptics were used as
      specific treatments for TD, although the need for additional neuroleptics was
      significantly lower in the quetiapine group (n=47, RR 0.49 CI 0.2 to 1.0) than in
      those given haloperidol. AUTHORS' CONCLUSIONS: Limited data from small studies
      using neuroleptic reduction or specific neuroleptic drugs as treatments for TD
      did not provide any convincing evidence of the value of these approaches. There
      is a need for larger trials of a longer duration in order to fully investigate
      this area.

PMID- 16437426
TI  - Inhaled nitric oxide for respiratory failure in preterm infants.
AB  - BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with
      hypoxic respiratory failure. The pathophysiology of respiratory failure, and the
      potential risks, differ substantially in preterm infants. Analysis of the
      efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks
      is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn
      infants (< 35 weeks gestation) who have hypoxic respiratory failure, treatment
      with inhaled nitric oxide improves oxygenation within 2 hours and reduces the
      rates of death, bronchopulmonary dysplasia, intraventricular haemorrhage, or
      neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane
      Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library),
      using the following keywords: nitric oxide, clinical trial, newborn, and covering
      years from 1985 to 2005. In addition, we searched the abstracts of the Pediatric
      Academic Societies. SELECTION CRITERIA: Randomised and quasi randomised studies
      in preterm infants with hypoxic respiratory failure. Administration of inhaled
      nitric oxide compared to control with or without placebo. Clinically relevant
      outcomes that were analysed included death, bronchopulmonary dysplasia (defined
      as oxygen dependence at 36 weeks postconceptional age), intraventricular
      haemorrhage, long term neurodevelopmental outcome and short term effects on
      oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane
      Neonatal Review Group were used. Two investigators extracted, assessed and coded
      separately all data for each study. Any disagreement was resolved by discussion.
      MAIN RESULTS: Seven randomised controlled trials of inhaled nitric oxide therapy
      in preterm infants were found. One study consisted of infants determined to have
      a high risk of developing bronchopulmonary dysplasia (Subhedar 1997). One study
      studied routine use of inhaled NO in all ventilated preterm infants (Schreiber
      2003). The remaining studies consisted of infants with high predicted mortality
      based on poor oxygenation (Kinsella 1999; Hascoet 2005; INNOVO 2005; Van Meurs
      2005; Mercier 1999). No significant effect of inhaled nitric oxide on mortality
      or bronchopulmonary dysplasia was demonstrated. There was no evidence of effect
      on the risk of intraventricular haemorrhage. There may be short term improvements
      in oxygenation. Two studies (Schreiber 2003; INNOVO 2005) have so far presented
      data on long term neurodevelopmental outcome, one of which demonstrated improved
      outcome at two years corrected age. AUTHORS' CONCLUSIONS: The currently published
      evidence from randomised trials does not support the use of inhaled nitric oxide
      in preterm infants with hypoxic respiratory failure. Further studies may need to
      be performed to evaluate the potential benefit of routine use of this therapy in
      infants with milder forms of respiratory failure, and these trials will need to
      be designed to evaluate not only neonatal survival, and the occurrence of
      neonatal morbidities, but should be powered to evaluate neurodevelopmental
      outcome at a minimum of two years of age.

PMID- 16437427
TI  - Echinacea for preventing and treating the common cold.
AB  - BACKGROUND: Preparations of the plant Echinacea (family Compositae) are widely
      used in some European countries and in North America for common colds. Most
      consumers and physicians are not aware that products available under the term
      Echinacea differ appreciably in their composition, mainly due to the use of
      variable plant material, extraction methods and addition of other components.
      OBJECTIVES: The objective of this review was to assess whether there is evidence
      that Echinacea preparations are 1) more effective than no treatment; 2) more
      effective than placebo; 3) similarly effective to other treatments in A) the
      prevention and B) the treatment of the common cold. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library Issue 3, 2005); PubMed (1997 to April 2005), EMBASE (1998 to June 2005),
      AMED (to August 2005), Centre for Complementary Medicine Research (in Munich)
      (1988 to May 2005), contacted experts, and screened references of reviews.
      SELECTION CRITERIA: We included randomized controlled trials that compared mono
      preparations of Echinacea with a placebo, no treatment, or another treatment for
      the prevention or treatment of common colds. Trials on combinations of Echinacea
      and other herbs were excluded. DATA COLLECTION AND ANALYSIS: For all studies, at
      least two authors independently assessed eligibility and trial quality, and
      extracted data. Outcomes of interest in prevention trials were: numbers of
      individuals with one or more colds, and severity and duration of colds; and in
      treatment trials: total symptom scores, nasal symptoms, and duration of colds.
      MAIN RESULTS: Sixteen trials including a total of 22 comparisons of an Echinacea
      preparation and a control group (19 with placebo, 2 with no treatment, 1 with
      another herbal preparation) met the inclusion criteria. All trials except one
      were described as double-blind. The majority had reasonable to good
      methodological quality. Three comparisons investigated prevention of colds and 19
      comparisons tested treatment of colds. A variety of different Echinacea
      preparations were used. None of the three comparisons in the prevention trials
      showed an effect over placebo. Comparing an Echinacea preparation with placebo as
      treatment, a significant effect was reported in nine comparisons, a trend in one,
      and no difference in six. More than one trial was available only for preparations
      based on the aerial parts from Echinacea purpurea (E. purpurea). AUTHORS'
      CONCLUSIONS: Echinacea preparations tested in clinical trials differ greatly.
      There is some evidence that preparations based on the aerial parts of Echinacea
      purpurea might be effective for the early treatment of colds in adults but
      results are not fully consistent. Beneficial effects of other Echinacea
      preparations, and for preventative purposes might exist but have not been shown
      in independently replicated, rigorous randomized trials.

PMID- 16437428
TI  - Lamotrigine versus carbamazepine monotherapy for epilepsy.
AB  - BACKGROUND: The choice of an antiepileptic drug (AED) for any individual should
      take into account reliable information about seizure control, adverse effects and
      cost. Carbamazepine is the usual drug of choice for people with newly-diagnosed
      partial onset seizures. Lamotrigine is a relatively new AED which is licensed in
      many countries for use as an initial monotherapy. OBJECTIVES: To review the best
      evidence comparing carbamazepine and lamotrigine when used as monotherapy in
      people with partial onset seizures, or generalized onset tonic-clonic seizures
      with or without other generalized seizure types. SEARCH STRATEGY: We searched the
      Cochrane Epilepsy Group's Specialized Register (July 2005), the Cochrane Central
      Register of Controlled Trials (CENTRAL) (TheCochraneLibrary Issue 2, 2005), and
      MEDLINE (1966 to August 2005). No language restrictions were imposed. We also
      contacted pharmaceutical companies and trial investigators. SELECTION CRITERIA:
      Randomized controlled trials, blinded or unblinded, in which children or adults
      with partial onset seizures or generalized onset tonic-clonic seizures were
      randomized to monotherapy with either carbamazepine or lamotrigine. DATA
      COLLECTION AND ANALYSIS: This was an individual patient data review. Outcomes
      were (1) time to treatment withdrawal, (2) time to first seizure post
      randomization, and (3) seizure freedom at six months. Time to event data were
      analysed using a stratified logrank analysis with results expressed as hazard
      ratios (HR) and 95% confidence intervals (95% CI); binary data were expressed as
      relative risks (RR) and 95% confidence intervals (95% CI). A HR or a RR greater
      than 1 indicated an event was more likely on lamotrigine than carbamazepine. MAIN
      RESULTS: Individual patient data were available for 1384 participants (100% of
      total randomized) from the five trials that met our inclusion criteria. The main
      results (HR (95% CI)) were (1) time to treatment withdrawal 0.55 (0.35 to 0.84)
      (random-effects), (2) time to first seizure post randomization 1.14 (95% CI 0.92
      to 1.43), and (3) seizure freedom at six months RR 0.92 (95% CI 0.81 to 1.04).
      The review suggested that time to treatment withdrawal was significantly improved
      with lamotrigine compared to carbamazepine, while time to first seizure and
      seizure freedom at six months favoured carbamazepine although the results were
      not statistically significant. AUTHORS' CONCLUSIONS: Lamotrigine was
      significantly less likely to be withdrawn than carbamazepine but results for time
      to first seizure suggested that carbamazepine may be superior in terms of seizure
      control. Trials were of too short a duration to measure important seizure
      outcomes such as time to 12 month remission. Further trials are needed in which
      longer-term outcome is assessed as well as measures such as psychosocial outcome
      and quality of life.

PMID- 16437429
TI  - Continuous positive airways pressure for obstructive sleep apnoea in adults.
AB  - BACKGROUND: Obstructive sleep apnoea is the periodic reduction (hypopnoea) or
      cessation (apnoea) of breathing due to narrowing or occlusion of the upper airway
      during sleep. The main symptom is daytime sleepiness and it has been suggested it
      is linked to premature death, hypertension, ischaemic heart disease, stroke and
      road traffic accidents. OBJECTIVES: The main treatment for sleep apnoea is with
      the use of continuous positive airways pressure (CPAP), which requires a flow
      generator and mask. These are used at night to prevent apnoea, hypoxia and sleep
      disturbance. The objective was to assess the effects of CPAP in the treatment of
      obstructive sleep apnoea in adults. SEARCH STRATEGY: We searched the Cochrane
      Airways Group Trials Register and reference lists of articles. We consulted
      experts in the field. Searches were current to July 2005. SELECTION CRITERIA: We
      included randomised trials comparing nocturnal CPAP with an inactive control or
      oral appliances in adults with obstructive sleep apnoea (an apnoea and hypopnoea
      index greater than five per hour). Trials had a minimum intervention period of
      two weeks. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two
      review authors extracted data independently. Study authors were contacted for
      missing information. Parallel and crossover group trials were analysed
      separately. MAIN RESULTS: Thirty-six trials involving 1718 people met the
      inclusion criteria. Study quality was mixed. Compared with control, CPAP showed
      significant improvements in objective and subjective sleepiness and several
      quality of life, cognitive function and depression measures (parallel-group
      studies: Epworth sleepiness scale (ESS) -3.83 units, 95% CI -4.57 to -3.09;
      crossover studies: ESS -1.84 units, 95% CI -2.57 to -1.11). Twenty-four hour
      systolic and diastolic blood pressures were lower with CPAP compared with control
      (parallel-group trials). Compared with oral appliances, CPAP significantly
      reduced the apnoea and hypopnoea index (crossover studies: -7.97 events/hr, 95%
      CI -9.56 to -6.38) and improved sleep efficiency (crossover studies: 2.31%, 95%
      CI 0.02 to 4.6) and minimum oxygen saturation (4.14%, 95% CI 3.25 to 5.03).
      Responders to both treatments expressed a strong preference for the oral
      appliance. However, participants were more likely to withdraw on OA than on CPAP
      therapy. AUTHORS' CONCLUSIONS: CPAP is effective in reducing symptoms of
      sleepiness and improving quality of life measures in people with moderate and
      severe obstructive sleep apnoea (OSA). It is more effective than oral appliances
      in reducing respiratory disturbances in these people but subjective outcomes are
      more equivocal. Certain people tend to prefer oral appliances to CPAP where both
      are effective. This could be because they offer a more convenient way of
      controlling OSA. Short-term data indicate that CPAP leads to lower blood pressure
      than in controls. Long-term data are required for all outcomes in order to
      determine whether the initial benefits seen in short-term clinical trials
      persist.

PMID- 16437430
TI  - Donepezil for dementia due to Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease is the most common cause of dementia in older
      people. One of the aims of therapy is to inhibit the breakdown of a chemical
      neurotransmitter, acetylcholine, by blocking the relevant enzyme. This can be
      done by a group of chemicals known as cholinesterase inhibitors. OBJECTIVES: The
      objective of this review is to assess whether donepezil improves the well-being
      of patients with dementia due to Alzheimer's disease. SEARCH STRATEGY: The
      Cochrane Dementia and Cognitive Improvement Group's Specialized Register was
      searched using the terms 'donepezil', 'E2020' and 'Aricept' on 12 June 2005. This
      Register contains up-to-date records of all major health care databases and many
      ongoing trial databases. Members of the Donepezil Study Group and Eisai Inc were
      contacted. SELECTION CRITERIA: All unconfounded, double-blind, randomized
      controlled trials in which treatment with donepezil was compared with placebo for
      patients with mild, moderate or severe dementia due to Alzheimer's disease. DATA
      COLLECTION AND ANALYSIS: Data were extracted by one reviewer (JSB), pooled where
      appropriate and possible, and the pooled treatment effects, or the risks and
      benefits of treatment estimated. MAIN RESULTS: 23 trials are included, involving
      5272 participants. Most trials were of 6 months or less duration in selected
      patients. Available outcome data cover domains including cognitive function,
      activities of daily living, behaviour , global clinical state and health care
      resource costs. For cognition there is a statistically significant improvement
      for both 5 and 10 mg/day of donepezil at 24 weeks compared with placebo on the
      ADAS-Cog scale (-2.01 points MD, 95%CI -2.69 to -1.34, p<0.00001); -2.80 points,
      MD 95% CI -3.74 to -2.10, p<0.00001) and for 10 mg/day donepezil compared with
      placebo at 52 weeks (1.84 MMSE points, 95% CI, 0.53 to 3.15, p=0.006). The
      results show some improvement in global clinical state (assessed by a clinician)
      in people treated with 5 and 10 mg/day of donepezil compared with placebo at 24
      weeks for the number of patients showing improvement or no change (OR 2.18, 95%
      CI 1.53 to 3.11, p=<0.0001, OR 2.38, 95% CI 1.78 to 3.19, p<0.00001). Benefits of
      treatment were also seen on measures of activities of daily living and behaviour,
      but not on the quality of life score . There were significantly more withdrawals
      before the end of treatment from the 10 mg/day (but not the 5 mg/day) donepezil
      group compared with placebo which may have resulted in some overestimation of
      beneficial changes at 10 mg/day. Benefits on the 10 mg/day dose were marginally
      larger than on the 5 mg/day dose. Two studies presented results for health
      resource use, and the associated costs. There were no significant differences
      between treatment and placebo for any item, the cost of any item, and for the
      total costs, and total costs including the informal carer costs. A variety of
      adverse effects were recorded, with more incidents of nausea, vomiting,
      diarrhoea, muscle cramps, dizziness, fatigue and anorexia (significant risk
      associated with treatment) in the 10 mg/day group compared with placebo but very
      few patients left a trial as a direct result of the intervention. AUTHORS'
      CONCLUSIONS: People with mild, moderate or severe dementia due to Alzheimer's
      disease treated for periods of 12, 24 or 52 weeks with donepezil experienced
      benefits in cognitive function, activities of daily living and behaviour. Study
      clinicians rated global clinical state more positively in treated patients, and
      measured less decline in measures of global disease severity. There is some
      evidence that use of donepezil is neither more nor less expensive compared with
      placebo when assessing total health care resource costs. Benefits on the 10
      mg/day dose were marginally larger than on the 5 mg/day dose. Taking into
      consideration the better tolerability of the 5 mg/day donepezil compared with the
      10 mg/day dose, together with the lower cost, the lower dose may be the better
      option. The debate on whether donepezil is effective continues despite the
      evidence of efficacy from the clinical studies because the treatment effects are
      small and are not always apparent in practice .

PMID- 16437431
TI  - Oral naltrexone maintenance treatment for opioid dependence.
AB  - BACKGROUND: Research on the clinical application of oral naltrexone agrees on
      several things. From a pharmacological perspective, naltrexone works. From an
      applied perspective, however, this medication is not used since the medication
      compliance and the retention rates are very poor. OBJECTIVES: To evaluate the
      effects of naltrexone maintenance treatment versus placebo or other treatments in
      preventing relapse in opioid addicts after detoxification. SEARCH STRATEGY: We
      searched the Cochrane Drugs and Alcohol Group Register of Trials (January 2005),
      Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library
      Issue 1, 2005), MEDLINE (1973-first year of naltrexone use in humans- January
      2005), EMBASE (1974- January 2005), PsycINFO (OVID-January 1985 to January 2004).
      We inspected reference lists of relevant articles and we contacted pharmaceutical
      producers of naltrexone, authors and other Cochrane review groups. SELECTION
      CRITERIA: All randomised and controlled clinical trials which focus on the use of
      naltrexone maintenance treatment versus placebo, or other treatments to reach
      sustained abstinence from opiate drugs DATA COLLECTION AND ANALYSIS: Three
      reviewers independently assessed studies for inclusion and extracted data. One
      reviewer carried out the qualitative assessments of the methodology of eligible
      studies using validated checklists. MAIN RESULTS: Ten studies, 696 participants,
      met the criteria for inclusion in this review. Only two studies described an
      adequate allocation concealment. The results show that naltrexone maintenance
      therapy alone or associated with psychosocial therapy is more efficacious that
      placebo alone or associated with psychosocial therapy in limiting the use of
      heroin during the treatment (RR 0,72 95% confidence interval 0.58 to 0.90). If we
      consider only the studies comparing naltrexone with placebo, the difference do
      not reach the statistical significancy, RR 0.79 (95%CI 0.59 to 1.06). With
      respect to the number of participants re incarcerated during the study period,
      the naltrexone associated with psychosocial therapy is more effective than the
      psychosocial treatment alone; RR 0.50 (95%CI 0.27 to 0.91). No statistically
      significant benefit was shown in terms of retention in treatment, side effects or
      relapse results at follow-up for any of the considered comparisons. AUTHORS'
      CONCLUSIONS: Unfortunately the studies did not provide an objective evaluation of
      naltrexone treatment in the field of opioid dependence. The conclusions are also
      limited due to the heterogeneity of the trials both in the interventions and in
      the assessment of outcomes.

PMID- 16437432
TI  - Duration of treatment with vitamin K antagonists in symptomatic venous
      thromboembolism.
AB  - BACKGROUND: Currently, the most frequently used secondary treatment for patients
      with venous thromboembolism is vitamin K antagonists targeted at an INR of 2.5
      (range 2.0 to 3.0). However, based on the continuing risk of bleeding and
      uncertainty regarding the risk of recurrent venous thromboembolism, there is
      discussion on the proper duration of treatment with vitamin K antagonists for
      these patients. Recently, several studies were published in which the risk and
      benefits of different durations of oral anticoagulants were compared in patients
      with venous thromboembolism. OBJECTIVES: The objective of this review was to
      evaluate efficacy and safety of different durations of treatment with vitamin K
      antagonists in patients with symptomatic venous thromboembolism. SEARCH STRATEGY:
      The Cochrane Peripheral Vascular Diseases Group searched their Specialised
      Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The
      Cochrane Library Issue 3, 2005). The Specialised Register is constructed from
      electronic searches of MEDLINE (from inception to October 2005) and EMBASE
      (inception to October 2005) and through handsearching relevant journals. In
      addition, we also contacted colleagues for details of trials. The last searches
      were carried out on 11 October 2005. SELECTION CRITERIA: Randomized controlled
      clinical trials comparing different durations of treatment with vitamin K
      antagonists in patients with symptomatic venous thromboembolism. DATA COLLECTION
      AND ANALYSIS: Two reviewers (BH and MP) extracted the data and assessed the
      quality of the trials independently. MAIN RESULTS: Eight studies with a total of
      2994 patients were included. A consistent reduction in the risk of recurrent
      events was observed during prolonged treatment with vitamin K antagonists (OR
      0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index
      thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly
      after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91
      to 1.69). In addition, a substantial increase in bleeding complications was found
      during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61).
      AUTHORS' CONCLUSIONS: In conclusion, this meta-analysis shows that treatment with
      vitamin K antagonists reduces the risk of recurrent venous thromboembolism for as
      long as it is used. However, the absolute risk of recurrent venous
      thromboembolism declines over time, while the risk for major bleeding remains.
      Thus, the efficacy of vitamin K antagonist administration decreases over time
      since the index event.

PMID- 16437433
TI  - Interventions for chronic palmoplantar pustulosis.
AB  - BACKGROUND: Chronic palmoplantar pustulosis (PPP) is a chronic inflammatory skin
      condition characterised by crops of sterile pustules (yellow pus spots) on the
      palms and soles which erupt repeatedly over months or years. The affected areas
      tend to become red and scaly; cracks may form and these are often painful. Many
      different treatments have been used for palmoplantar pustulosis but none is
      generally accepted as being reliably effective. OBJECTIVES: To assess the effects
      of treatments for palmoplantar pustulosis, both in reducing disease severity and
      in maintaining remission once achieved. SEARCH STRATEGY: We searched the Cochrane
      Skin Group Specialised Register (January 2003), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to February
      2003), EMBASE (1988 to February 2003). We also cross-checked with the Salford
      Database of Psoriasis Trials and reference lists of articles. We also contacted
      authors included trials, members of the Cochrane Skin Group and dermatologists
      interested in psoriasis. SELECTION CRITERIA: Any randomised controlled trial in
      which patients with chronic palmoplantar pustulosis were randomised to receive
      one or more interventions. DATA COLLECTION AND ANALYSIS: At least two reviewers
      independently assessed trial eligibility and quality. Study authors were
      contacted for additional information. Adverse effects information was collected
      from the trials. MAIN RESULTS: Twenty-three trials involving 724 people were
      included. There is evidence supporting the use of systemic retinoids (improvement
      rate difference 44%, 95 CI 28 to 59%), oral PUVA (improvement rate difference
      44%, 95 CI 26 to 62%). However, a combination of PUVA and retinoids is better
      than the individual treatments. The use of topical steroid under hydrocolloid
      occlusion is beneficial. It would also appear that low dose ciclosporin,
      tetracycline antibiotics and Grenz Ray Therapy may be useful in treating PPP.
      Colchicine has a lot of side effects and it is unclear if it is effective and
      neither was topical PUVA (rate difference of 0.00, 95% CI -0.04 to +0.04). There
      is no evidence to suggest that short-term treatment with hydroxycarbamide
      (hydroxyurea) is effective. AUTHORS' CONCLUSIONS: Many different interventions
      were reported to produce "improvement" in PPP. There is, however, no standardised
      method for assessing response to treatment, and reductions in pustule counts or
      other empirical semi-quantitative scoring systems may be of little relevance to
      the patient. This review has shown that the ideal treatment for PPP remains
      elusive and that the standards of study design and reporting need to be improved
      to inform patients and those treating them of the relative merits of the many
      treatments available to them.

PMID- 16437434
TI  - Holding chambers versus nebulisers for inhaled steroids in chronic asthma.
AB  - BACKGROUND: Inhaled corticosteroids are available in the form of a suspension for
      nebulisation, although the role of this mode of therapy in the treatment of
      chronic asthma is still unclear. OBJECTIVES: To assess the efficacy and safety of
      inhaled corticosteroids delivered via nebuliser versus holding chamber for the
      treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways
      Group Trial Register (1999) and reference lists of articles. We contacted the
      authors of studies and pharmaceutical companies for additional studies and hand
      searched the British Journal of Clinical Research, European Journal of Clinical
      Research and major respiratory society meeting abstracts (1997-1999). Date of
      last search August 2005. SELECTION CRITERIA: Randomised controlled trials
      comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids
      for the treatment of chronic asthma. All age groups of patients were considered.
      Two reviewers assessed articles for inclusion; two reviewers independently
      assessed included studies for methodological quality. DATA COLLECTION AND
      ANALYSIS: One reviewer extracted data; authors were contacted to clarify missing
      information. Quantitative analyses were undertaken using Review Manager 4.1 with
      MetaView 3.1. MAIN RESULTS: Two studies were selected for inclusion (63
      subjects), both concerned adults. An additional small study including 14 children
      was identified for the 2005 update. Methodological quality was variable. Due to
      design differences it was not appropriate to pool the studies. The single high
      quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy
      jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large
      volume spacer. The nebuliser delivery led to higher morning peak expiratory flow
      values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue
      beta2 agonist use and symptom scores compared to the holding chamber delivery.
      AUTHORS' CONCLUSIONS: Budesonide in high dose delivered by the particular
      nebuliser used in the only double-blinded study that could be included in this
      review was more effective than budesonide 1600 mcg via a large volume spacer.
      However, it is not clear whether this was an effect of nominal dose delivered or
      delivery system. Cost, compliance and patient preference are important
      determinants of clinical effectiveness that still require further assessment.
      Future studies are needed to evaluate the relative effectiveness of inhaled
      corticosteroids delivered by different combinations of nebuliser/compressor
      compared to holding chamber. Moreover, further studies assessing these delivery
      methods are needed in infants and pre-school children, as these are groups that
      are likely to be considered for treatment with nebulised corticosteroids.

PMID- 16437435
TI  - Surgery for nonarteritic anterior ischemic optic neuropathy.
AB  - BACKGROUND: Nonarteritic ischemic optic neuropathy is characterized by sudden and
      painless loss of vision in the eye, accompanied by pallid swelling of the optic
      disc. No medical therapy has been proven effective in treating this condition.
      OBJECTIVES: The objective of this review is to assess the safety and efficacy of
      surgery compared with other treatment or usual care in people with nonarteritic
      ischemic optic neuropathy. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and
      Vision Group Trials Register, in The Cochrane Library, MEDLINE, EMBASE and the UK
      National Research Register (NRR). The last search was on 13 July 2005. SELECTION
      CRITERIA: We included randomized controlled trials. DATA COLLECTION AND ANALYSIS:
      We obtained full copies of all potentially relevant articles. One randomized
      trial was eligible for inclusion. One author extracted data which was verified by
      another author. No synthesis was required. MAIN RESULTS: The one included trial
      randomized 258 participants and was stopped early. At the time of the 24-month
      report the follow-up rate was 95.3% for six months and 67.4% for 24 months (174
      participants, 89 careful follow up and 85 surgery). There was no evidence of a
      benefit of surgery on visual acuity. At six months 32.0% of the surgery group had
      improved visual acuity by three or more lines compared with 42.6% of the careful
      follow up group (unadjusted risk ratio (RR) 0.75, 95% confidence interval (CI)
      0.54 to 1.04). At 24 months 29.4% of the surgery group had improved compared with
      31.0% of the careful follow up group (unadjusted RR 0.95, 95% CI 0.60 to 1.49).
      Participants who underwent surgery had a greater risk of losing three or more
      lines of vision. At six months 18.9% in the surgery group had worsened compared
      with 14.8% in the careful follow up group (RR 1.28; 95% CI 0.73 to 2.24). At 24
      months 20.0% in the surgery group had worsened compared with 21.8% in the careful
      follow up group (RR 0.92; 95% CI 0.51 to 1.64). AUTHORS' CONCLUSIONS: Results
      from the single trial indicate no evidence of a beneficial effect of optic nerve
      decompression surgery for nonarteritic ischemic optic neuropathy.

PMID- 16437436
TI  - Galantamine for Alzheimer's disease and mild cognitive impairment.
AB  - BACKGROUND: Galantamine is a specific, competitive, and reversible
      acetylcholinesterase inhibitor. OBJECTIVES: To assess the clinical effects of
      galantamine in patients with mild cognitive impairment (MCI), probable or
      possible Alzheimer's disease (AD), and potential moderators of effect. SEARCH
      STRATEGY: The trials were identified from a search of the Specialized Register of
      the Cochrane Dementia and Cognitive Improvement Group, last updated on 25 April
      2005 using the terms galanthamin*, galantamin* and Reminyl. Published reviews
      were inspected for further sources. Additional information was collected from
      unpublished clinical research reports for galantamine obtained from Janssen and
      from http://www.clinicalstudyresults.org/. SELECTION CRITERIA: Trials selected
      were randomised, double-blind, parallel-group comparisons of galantamine with
      placebo for a treatment duration of greater than 4 weeks in subjects with MCI or
      AD. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the
      reviewers and pooled where appropriate and possible. Outcomes of interest include
      the clinical global impression of change (CIBIC-plus or CGIC), Alzheimer's
      Disease Assessment Scale-cognitive sub scale (ADAS-cog), Alzheimer's Disease
      Cooperative Study/Activities of Daily Living (ADCS-ADL), Disability Assessment
      for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). Potential
      moderating variables of treatment effect assessed included trial duration, dose,
      and diagnosis of possible versus probable Alzheimer's disease. MAIN RESULTS: Ten
      trials with a total 6805 subjects were included in the analysis. Treatment with
      galantamine led to a significantly greater proportion of subjects with improved
      or unchanged global rating scale rating (k = 8 studies), at all dosing levels
      except for 8 mg/d . Confidence intervals for the ORs overlapped across the dose
      range of 16 mg to 36 mg per day, with point estimates of 1.6 - 1.8 when analysed
      with the intention-to-treat sample. Treatment with galantamine also led to
      significantly greater reduction in ADAS-cog score at all dosing levels (k = 8),
      with greater effect over six months compared to three months. Confidence
      intervals again overlapped. Point estimate of effect was lower for 8 mg/d but
      similar for 16 mg to 36 mg per day. For example, treatment effect for 24 mg/d
      over six months was 3.1 point reduction in ADAS-cog (95%CI 2.6-3.7, k = 4,
      ITT).ADCS-ADL, DAD and NPI were reported only in a small proportion of trials:
      all showed significant treatment effect in some individual trials at least.
      Confidence interval of treatment effect for the one trial recruiting patients
      with possible AD overlapped with the other seven recruiting patients with
      probable AD. Galantamine's adverse effects appeared similar to those of other
      cholinesterase inhibitors and to be dose related. Prolong release / once daily
      formulation of galantamine at 16 - 24mg/d was found to have similar efficacy and
      side-effect profile as the equivalent twice-daily regime. Data from the two MCI
      trials suggest marginal clinical benefit, but a yet unexplained excess in death
      rate. AUTHORS' CONCLUSIONS: Subjects in these trials were similar to those seen
      in earlier anti dementia AD trials, consisting primarily of mildly to moderately
      impaired outpatients. Galantamine's effect on more severely impaired subjects has
      not yet been assessed.Nevertheless, this review shows consistent positive effects
      for galantamine for trials of three to six months' duration. Although there was
      not a statistically significant dose-response effect, doses above 8 mg/d were,
      for the most part, consistently statistically significant. Galantamine's safety
      profile in AD is similar to that of other cholinesterase inhibitors with respect
      to cholinergically mediated gastrointestinal symptoms. It appears that doses of
      16 mg/d were best tolerated in the single trial where medication was titrated
      over a four week period, and because this dose showed statistically
      indistinguishable efficacy with higher doses, it is probably most preferable
      initially. Longer term use of galantamine has not been assessed in a controlled
      fashion. Galantamine use in MCI is not recommended due to its association with an
      excess death rate.

PMID- 16437437
TI  - Assisted hatching on assisted conception (IVF & ICSI).
AB  - BACKGROUND: Failure of implantation and conception may result from an inability
      of the blastocyst to escape from its outer coat, know as the zona pellucida. In
      vitro culture conditions and/or advancing maternal age may alter the architecture
      of the zona pellucida and result in hatching difficulties. Artificial disruption
      of this coat is known as assisted hatching (AH) has been proposed as a method of
      improving the success of assisted conception. OBJECTIVES: To determine whether
      assisted hatching (AH) of embryos facilitates live births and clinical pregnancy
      and whether it impacts on negative outcomes (such as multiple pregnancy and
      miscarriage). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and
      Subfertility Group trials register (1 June 2005), the Cochrane Controlled Trials
      Register (Cochrane Library Issue 2, 2005), MEDLINE (1996 to June 2003), EMBASE
      (1980 to June 2005) and reference lists of articles. Authors were contacted for
      missing and/or unpublished data. SELECTION CRITERIA: Trials were identified and
      independently screened by two reviewers. Randomised controlled trials of AH
      (mechanical, chemical or laser disruption of the zona pellucida prior to embryo
      replacement) versus no AH that reported live birth, clinical pregnancy or
      implantation rates were included. DATA COLLECTION AND ANALYSIS: Qualitative
      assessments and data extraction were performed independently by two reviewers.
      Outcomes were extracted as rates and combined using random effects meta-analysis,
      sensitivity analysis, sub grouping and meta-regression where appropriate. MAIN
      RESULTS: Twenty-three randomised controlled trials consisting of 2668 women
      reported on 849 pregnancy outcomes. There was no significant difference in the
      odds of live births in the AH compared with control groups (6 RCTs; OR 1.19 95%
      CI 0.81 to 1.73; 163 births from 516 women). Women undergoing assisted hatching
      were significantly more likely to achieve clinical pregnancy (23 RCTs, OR 1.33,
      95% CI 1.12 to 1.57). Miscarriage rates per woman were similar in both groups (12
      RCTs OR 1.23 (95% CI 0.73 to 2.05). Multiple pregnancy rates per woman was
      increased in women who were randomised to AH compared with control women (9 RCTs
      OR 1.83 (95% CI 1.19 to 2.83). The improvement in clinical pregnancy rate means
      for a clinic with a success rate of 25% could anticipate improving the CPR to
      between 28 and 39%, all things being equal. The trials provided insufficient data
      to investigate the impact of assisted hatching on several important outcomes,
      including monozygotic twinning, embryo damage, congenital and chromosomal
      abnormalities, and in vitro blastocyst development. AUTHORS' CONCLUSIONS: Despite
      significantly improved odds of clinical pregnancy, there is insufficient evidence
      to determine any effect of AH on live birth rates. The increased multiple
      pregnancy rate is of concern although it likely that with a policy of single
      embryo transfer this may be lowered. Currently, there is insufficient evidence to
      recommend assisted hatching.

PMID- 16437438
TI  - Opioid antagonists with minimal sedation for opioid withdrawal.
AB  - BACKGROUND: Managed withdrawal is necessary prior to drug-free treatment. It may
      also represent the end point of long-term opioid replacement treatment.
      OBJECTIVES: To assess the effectiveness of opioid antagonists in combination with
      minimal sedation to induce withdrawal, in terms of intensity of withdrawal,
      adverse effects and completion of treatment. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3,
      2005, which includes the Cochrane Drugs and Alcohol Group register), MEDLINE
      (January 1966 to August 2005), EMBASE (January 1985 to August 2005), PsycINFO
      (1967 to August 2005), and CINAHL (1982 to July 2005) and reference lists of
      articles. SELECTION CRITERIA: Experimental interventions involved the use of
      opioid antagonists in combination with minimal sedation to manage withdrawal in
      opioid-dependent participants compared with other approaches or different opioid
      antagonist regime. DATA COLLECTION AND ANALYSIS: One reviewer assessed studies
      for inclusion and undertook data extraction and trial quality. Study authors were
      contacted for additional information. MAIN RESULTS: Nine studies (5 randomised
      controlled trials), involving 775 participants, met the inclusion criteria for
      the review. Withdrawal induced by opioid antagonists in combination with an
      adrenergic agonist is more intense than withdrawal managed with clonidine or
      lofexidine alone, but the overall severity is less. Limited data showed that
      antagonist-induced withdrawal may be more severe when the last opioid used was
      methadone rather than heroin or another short-acting opioid. Delirium may occur
      following the first dose of opioid antagonist, particularly with higher doses (>
      25mg naltrexone). The studies included suggest there is no significant difference
      in rates of completion of treatment for withdrawal induced by opioid antagonists,
      in combination with an adrenergic agonist, compared with adrenergic agonist
      alone. AUTHORS' CONCLUSIONS: The use of opioid antagonists combined with alpha2
      adrenergic agonists is a feasible approach to the management of opioid
      withdrawal. However, it is unclear whether this approach reduces the duration of
      withdrawal or facilitates transfer to naltrexone treatment to a greater extent
      than withdrawal managed primarily with an adrenergic agonist.A high level of
      monitoring and support is desirable for several hours following administration of
      opioid antagonists because of the possibility of vomiting, diarrhoea and
      delirium. Further research is required to confirm the relative effectiveness of
      antagonist-induced regimes, as well as variables influencing the severity of
      withdrawal, adverse effects, the most effective antagonist-based treatment
      regime, and approaches that might increase retention in subsequent naltrexone
      maintenance treatment.

PMID- 16437439
TI  - Intravenous immunoglobulin for Guillain-Barre syndrome.
AB  - BACKGROUND: Guillain-Barre syndrome is an acute, paralysing, inflammatory
      peripheral nerve disease. Intravenous immunoglobulin is beneficial in other
      autoimmune diseases. OBJECTIVES: We aimed to determine the efficacy of
      intravenous immunoglobulin for treating Guillain-Barre syndrome. SEARCH STRATEGY:
      We searched the Cochrane Neuromuscular Disease Group Trials Register (March
      2005), MEDLINE (January 1966 to March 2005) and EMBASE (January 1980 to March
      2005) using the terms 'Guillain-Barre syndrome' and 'acute polyradiculoneuritis'.
      SELECTION CRITERIA: We included all randomised and quasi-randomised trials. DATA
      COLLECTION AND ANALYSIS: Two authors independently selected papers, extracted
      data and assessed quality. MAIN RESULTS: Another Cochrane systematic review has
      shown that plasma exchange significantly hastens recovery. We found six
      randomised trials comparing intravenous immunoglobulin with plasma exchange. We
      undertook a meta-analysis of five trials involving 536, mostly adult participants
      who were unable to walk unaided and had been ill for less than two weeks. Our
      primary outcome measure was the change in a seven-grade disability scale four
      weeks after randomisation. The weighted mean difference of this measure was not
      statistically significant, being only -0.02 (95% confidence interval -0.25 to
      0.20) of a disability grade more improvement in the intravenous immunoglobulin
      than the plasma exchange group. There were no statistically significant
      differences in other measures. One trial involving 249 participants compared
      plasma exchange followed by intravenous immunoglobulin with plasma exchange
      alone. Another involving 37 participants compared immunoabsorption followed by
      intravenous immunoglobulin with immunoabsorption alone. Neither revealed
      significant extra benefit from intravenous immunoglobulin. One study with 39
      participants showed a trend towards more improvement with high-dose compared with
      low-dose intravenous immunoglobulin. Another trial with 51 children found no
      significant difference in outcome when the standard dose was given over two days
      rather than five days. Three studies including a total of 75 participants
      suggested that in children intravenous immunoglobulin significantly hastens
      recovery compared with supportive care. AUTHORS' CONCLUSIONS: In adults, there
      are no adequate comparisons with placebo. Randomised trials in severe disease
      show that intravenous immunoglobulin started within two weeks from onset hastens
      recovery as much as plasma exchange, which is known to be more effective than
      supportive care. Treatment with intravenous immunoglobulin is significantly more
      likely to be completed than plasma exchange. Giving intravenous immunoglobulin
      after plasma exchange did not confer significant extra benefit. In children,
      intravenous immunoglobulin probably hastens recovery compared with supportive
      care alone. More research is needed in mild disease and in treatment starting
      more than two weeks after onset of the condition. Dose-ranging studies are also
      needed.

PMID- 16437440
TI  - Combined chemotherapy and radiotherapy (without surgery) compared with
      radiotherapy alone in localized carcinoma of the esophagus.
AB  - BACKGROUND: Esophageal carcinoma can be managed primarily with either a surgical
      or non-surgical radiotherapeutic approach. Combination chemotherapy (CT) and
      radiotherapy (RT) has been incorporated into clinical practice and applied
      increasingly, especially in North America. OBJECTIVES: To evaluate combined CT
      and RT (CTRT) versus RT alone in patients with localized esophageal carcinoma.
      Outcomes included overall survival, cause-specific survival, local recurrence,
      dysphagia relief, quality of life, acute and chronic toxicities. SEARCH STRATEGY:
      The Cochrane strategy for identifying randomized trials was combined with
      relevant MeSH headings. The Cochrane Library, MEDLINE, CancerLIT and EMBASE were
      last searched in April 2005. References from relevant articles and personal files
      were included. SELECTION CRITERIA: Randomized controlled trials in patients with
      localized esophageal cancer comparing RT alone with combined CTRT were included.
      Studies comparing non-chemotherapy agents such as pure radiotherapy sensitisers,
      immunostimulants, planned esophagectomy, were excluded. DATA COLLECTION AND
      ANALYSIS: Two reviewers extracted data independently. Trial quality was assessed
      using the Jadad scale and Detsky checklist. Sensitivity analyses were planned to
      examine the effect of concomitant versus sequential treatment, study quality,
      radiotherapy dose, and whether the drug regimen contained cisplatin or 5
      fluorouracil were performed. MAIN RESULTS: Nineteen randomized trials were
      included, with eleven concomitant and eight sequential RTCT studies. Concomitant
      RTCT provided significant reduction in mortality with a harms ratio (HR) of 0.73
      (95% confidence interval (CI) 0.64 to 0.84). Using an estimated mortality rate
      for the control group of 62% at year one and 83% at year two, the absolute
      survival benefit for RTCT was 9% (95% CI 5 to 12%) and 4% (95% CI 3 to 6%])
      respectively. There was an absolute reduction of local recurrence rate of 12%
      (95% CI 3 to 22%), number needed to treat (NNT) of 9, when the local recurrence
      rate for the RT alone arm was 68%. This was associated with a significant risk of
      severe and life-threatening toxicities (number needed to harm (NNH)of 6).
      Sensitivity analyses did not identify any factors that interacted with the
      results. The results from sequential RTCT studies showed no significant benefit
      in survival or local control but significant toxicities. AUTHORS' CONCLUSIONS:
      Based on the available data, when a non-operative approach is selected then
      concomitant RTCT is superior to RT alone for patients with localized esophageal
      cancer but with significant toxicities. In patients who are in good general
      condition, and the risk benefit has been thoroughly discussed with the patient,
      concomitant RTCT should be considered for the management of esophageal cancer
      compared with radiotherapy alone.

PMID- 16437441
TI  - Proton pump inhibitor treatment for acute peptic ulcer bleeding.
AB  - BACKGROUND: Randomised controlled trials (RCTs) evaluating the clinical effect of
      proton pump inhibitors (PPIs) in peptic ulcer (PU) bleeding yield conflicting
      results. OBJECTIVES: To evaluate the efficacy of PPIs in acute bleeding from PU
      using evidence from RCTs. SEARCH STRATEGY: We searched CENTRAL, The Cochrane
      Library (Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to
      November 2004), proceedings of major meetings to November 2004, and reference
      lists of articles. We contacted pharmaceutical companies and experts in the
      field. SELECTION CRITERIA: RCTs of PPI treatment (oral or intravenous) compared
      with placebo or H(2)-receptor antagonist (H(2)RA) in acute bleeding from PU. DATA
      COLLECTION AND ANALYSIS: Two reviewers extracted data independently, assessed
      study validity, summarised studies and undertook meta-analysis. The influence of
      study characteristics on the outcomes was examined by subgroup analyses and meta
      regression. MAIN RESULTS: Twenty-four RCTs comprising 4373 participants in total
      were included. Statistical heterogeneity was found among trials for rebleeding (P
      = 0.04), but not for all-cause mortality (P = 0.24) or surgery (P = 0.45). There
      was no significant difference in all-cause mortality rates between PPI and
      control treatment; pooled rates were 3.9% on PPI versus 3.8% on control (odds
      ratio (OR) 1.01; 95% CI 0.74 to 1.40). PPIs significantly reduced rebleeding
      compared to control; pooled rates were 10.6% with PPI versus 17.3% with control
      treatment (OR 0.49; 95% CI 0.37 to 0.65). PPI treatment significantly reduced
      surgery compared with control; pooled rates were 6.1% on PPI versus 9.3% on
      control (OR 0.61; 95% CI 0.48 to 0.78). There was no evidence to suggest that
      results on mortality and rebleeding were dependent on study quality, route of PPI
      administration, type of control treatment or application of initial endoscopic
      haemostatic treatment. PPIs significantly reduced surgery compared with placebo
      but not when compared with H(2)RA. There was no evidence to suggest that study
      quality, route of PPI administration or application of initial endoscopic
      haemostatic treatment influenced results on surgery. PPI treatment appeared more
      efficacious in studies conducted in Asia compared to studies conducted elsewhere.
      All-cause mortality was reduced only in Asian studies; reductions in rebleeding
      and surgery were quantitatively greater in Asian studies. Among patients with
      active bleeding or non-bleeding visible vessel, PPI treatment reduced mortality
      (OR 0.53; 95% CI 0.31 to 0.91), rebleeding and surgery. AUTHORS' CONCLUSIONS: PPI
      treatment in PU bleeding reduces rebleeding and surgery compared with placebo or
      H(2)RA, but there is no evidence of an overall effect on all-cause mortality.

PMID- 16437442
TI  - Media-based behavioural treatments for behavioural problems in children.
AB  - BACKGROUND: Many approaches are used to address behavioural problems in childhood
      including medication or, more usually, psychological treatments either directly
      with the child and/or his/her family. Behavioural and cognitive-behavioural
      interventions have been shown to be highly effective but access to these
      treatments is limited due to factors such as time and expense. Presenting the
      information parents need in order to manage these behaviour problems in booklet
      or other media-based format would most likely reduce the cost and increase access
      to these interventions. OBJECTIVES: To review the effects of media-based
      cognitive-behavioural therapies for any young person with a behavioural disorder
      (diagnosed using a recognised instrument) compared to standard care and no
      treatment controls. SEARCH STRATEGY: The following electronic databases were
      systematically searched: CENTRAL (The Cochrane Library Issue 3, 2005), MEDLINE
      (1966 to August 2005), EMBASE (1980 to August 2005), PsycINFO (1887 to August
      2005), CINAHL (1982 to August 2005), Biosis (1985 to August 2005) and Sociofile
      (1974 to August 2005). References in all selected trials were checked for other
      trials and experts in the field were contacted for additional information.
      SELECTION CRITERIA: Randomised and quasi-randomised controlled trials (e.g.
      trials which used sequential randomisation) of media-based behavioural treatments
      for behaviour problems in children. DATA COLLECTION AND ANALYSIS: Abstracts and
      titles of studies identified from searches of electronic databases were read to
      determine whether they met the inclusion criteria. Full copies of those possibly
      meeting these criteria from electronic or other searches were assessed by the
      reviewers and queries were resolved by discussion. Data were analysed using
      RevMan 4.2. MAIN RESULTS: Eleven studies including 943 participants were included
      within this review. In general, media-based therapies for behavioural disorders
      in children had a moderate, if variable, effect when compared with both no
      treatment controls with effects sizes ranging from -0.12 (-1.65, 1.41) to -32.60
      (-49.93, -15.27) and as and adjunct to medication with effect sizes ranging from 
      2.71 (-5.86, -0.44) to -39.55 (-75.01, -4.09). Significant improvements were made
      with the addition of up to two hours of therapist time. AUTHORS' CONCLUSIONS:
      These formats of delivering behavioural interventions for carers of children are
      worth considering in clinical practice. Media-based interventions may, in some
      cases, be enough to make clinically significant changes in a child's behaviour,
      and may reduce the amount of time primary care workers have to devote to each
      case. They can also be used as the first stage of a stepped care approach.
      Consequently this would increase the number of families who could possibly
      benefit from these types of intervention, releasing clinician time that can be
      reallocated to more complex cases. Media-based therapies would therefore appear
      to have both clinical and economic implications as regards the treatment of
      children with behavioural problems.

PMID- 16437443
TI  - Retention procedures for stabilising tooth position after treatment with
      orthodontic braces.
AB  - BACKGROUND: Retention is the phase of orthodontic treatment that attempts to keep
      teeth in the corrected positions after treatment with orthodontic (dental)
      braces. Without a phase of retention there is a tendency for the teeth to return
      to their initial position (relapse). To prevent relapse almost every patient who
      has orthodontic treatment will require some type of retention. OBJECTIVES: To
      evaluate the effectiveness of different retention strategies used to stabilise
      tooth position after orthodontic braces. SEARCH STRATEGY: The Cochrane Oral
      Health Group's (OHG) Trials Register, CENTRAL, MEDLINE and EMBASE were searched.
      Handsearching of orthodontic journals was undertaken in keeping with the Cochrane
      OHG search programme. No language restrictions were applied. Authors of
      randomised controlled trials (RCTs) were identified and contacted to identify
      unpublished trials. Most recent search: May 2005. SELECTION CRITERIA: RCTs on
      children and adults, who have had retainers fitted or adjunctive procedures
      undertaken, following orthodontic treatment with braces to prevent relapse. The
      outcomes were: how well the teeth were stabilised, survival of retainers, adverse
      effects on oral health and quality of life. DATA COLLECTION AND ANALYSIS:
      Screening of eligible studies, assessment of the methodological quality of the
      trials and data extraction were conducted in duplicate and independently by two
      review authors. As no two studies compared the same retention strategies
      (interventions) it was not possible to combine the results of any studies. MAIN
      RESULTS: Five trials satisfied the inclusion criteria. These trials all compared
      different interventions: circumferential supracrestal fiberotomy (CSF) combined
      with full-time removable retainer versus a full-time removable retainer alone;
      CSF combined with a nights-only removable retainer versus a nights-only removable
      retainer alone; removable Hawley retainer versus a clear overlay retainer;
      multistrand wire retainer versus a ribbon-reinforced resin bonded retainer; and
      three types of fixed retainers versus a removable retainer. There was weak
      unreliable evidence, based on data from one trial, that there was a statistically
      significant increase in stability in both the mandibular (lower) (P < 0.001) and
      maxillary (upper) anterior segments (P < 0.001) when the CSF was used, compared
      with when it was not used. There was also weak, unreliable evidence that teeth
      settle quicker with a Hawley retainer than with a clear overlay retainer after 3
      months. The quality of the trial reports was generally poor. AUTHORS'
      CONCLUSIONS: There are insufficient research data on which to base our clinical
      practice on retention at present. There is an urgent need for high quality
      randomised controlled trials in this crucial area of orthodontic practice.

PMID- 16437444
TI  - Influenza vaccine for patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Influenza vaccinations are currently recommended in the care of
      people with COPD, but these recommendations are based largely on evidence from
      observational studies with very few randomised controlled trials (RCTs) reported.
      Influenza infection causes excess morbidity and mortality in COPD patients but
      there is also the potential for influenza vaccination to cause adverse effects or
      not to be cost effective. OBJECTIVES: To evaluate the evidence from RCTs for a
      treatment effect of influenza vaccination in COPD subjects. Outcomes of interest
      were exacerbation rates, hospitalisations, mortality, lung function and adverse
      effects. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised
      Register of trials, and reference lists of articles. References were also
      provided by a number of drug companies we contacted. SELECTION CRITERIA: RCTs
      that compared live or inactivated virus vaccines with placebo, either alone or
      with another vaccine in persons with COPD. Studies of people with asthma were
      excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. All entries
      were double checked. Study authors and drug companies were contacted for missing
      information. MAIN RESULTS: Eleven trials were included but only six of these were
      specifically performed in COPD patients. The others were conducted on elderly and
      high-risk individuals, some of whom had chronic lung disease. Inactivated vaccine
      in COPD patients resulted in a significant reduction in the total number of
      exacerbations per vaccinated subject compared with those who received placebo
      (weighted mean difference (WMD) -0.37, 95% confidence interval -0.64 to -0.11, P
      = 0.006). This was due to the reduction in "late" exacerbations occurring after
      three or four weeks (WMD -0.39, 95% CI -0.61 to -0.18, P = 0.0004). In Howells
      1961, the number of patients experiencing late exacerbations was also
      significantly less (odds ratio 0.13, 95% CI 0.04 to 0.45, P = 0.002). Both
      Howells 1961 and Wongsurakiat 2004 found that inactivated influenza vaccination
      reduced influenza -related respiratory infections (WMD 0.19, 95% CI 0.07 to 0.48,
      P = 0.0005). In both COPD patient and in elderly patients (only a minority of
      whom had COPD), there was a significant increase in the occurrence of local
      adverse reactions in vaccinees, but the effects were generally mild and
      transient. There was no evidence of an effect of intranasal live attenuated virus
      when this was added to inactivated intramuscular vaccination. The studies are too
      small to have detected any effect on mortality. An updated search conducted in
      September 2001 did not yield any further studies. A search in 2003 yielded two
      further reports of the same eligible study Gorse 2003. A search in 2004 yielded
      two reports of the another eligible study Wongsurakiat 2004. The author informed
      us of another report of the same study Wongsurakiat 2004/2. AUTHORS' CONCLUSIONS:
      It appears, from the limited number of studies performed, that inactivated
      vaccine reduces exacerbations in COPD patients. The size of effect was similar to
      that seen in large observational studies, and was due to a reduction in
      exacerbations occurring three or more weeks after vaccination, and due to
      influenza. There is a mild increase in transient local adverse effects with
      vaccination, but no evidence of an increase in early exacerbations.

PMID- 16437445
TI  - Pharmacotherapy for post traumatic stress disorder (PTSD).
AB  - BACKGROUND: Post traumatic stress disorder (PTSD) is a prevalent and disabling
      disorder. Evidence that PTSD is characterised by specific psychobiological
      dysfunctions has contributed to a growing interest in the use of medication in
      its treatment. OBJECTIVES: To assess the effects of medication for post traumatic
      stress disorder. SEARCH STRATEGY: We searched the Cochrane Depression, Anxiety
      and Neurosis Group specialised register (CCDANCTR-Studies) on 18 August 2005, the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      issue 4, 2004), MEDLINE (January 1966 to December 2004), PsycINFO (1966 to 2004),
      and the National PTSD Center Pilots database. Reference lists of retrieved
      articles were searched for additional studies. SELECTION CRITERIA: All randomised
      controlled trials (RCTs) of pharmacotherapy for PTSD. DATA COLLECTION AND
      ANALYSIS: Two raters independently assessed RCTs for inclusion in the review,
      collated trial data, and assessed trial quality. Investigators were contacted to
      obtain missing data. Summary statistics were stratified by medication class, and
      by medication agent for the selective serotonin reuptake inhibitors (SSRIs).
      Dichotomous and continuous measures were calculated using a random effects model,
      heterogeneity was assessed, and subgroup/sensitivity analyses were undertaken.
      MAIN RESULTS: 35 short-term (14 weeks or less) RCTs were included in the analysis
      (4597 participants). Symptom severity for 17 trials was significantly reduced in
      the medication groups, relative to placebo (weighted mean difference -5.76, 95%
      confidence intervals (CI) -8.16 to -3.36, number of participants (N) = 2507).
      Similarly, summary statistics for responder status from 13 trials demonstrated
      overall superiority of a variety of medication agents to placebo (relative risk
      1.49, 95% CI 1.28 to 1.73, number needed to treat = 4.85, 95% CI 3.85 to 6.25, N
      = 1272). Medication and placebo response occurred in 59.1% (N = 644) and 38.5%
      (628) of patients, respectively. Of the medication classes, evidence of treatment
      efficacy was most convincing for the SSRIs. Medication was superior to placebo in
      reducing the severity of PTSD symptom clusters, comorbid depression and
      disability. Medication was also less well tolerated than placebo. A narrative
      review of 3 maintenance trials suggested that long term medication may be
      required in treating PTSD. AUTHORS' CONCLUSIONS: Medication treatments can be
      effective in treating PTSD, acting to reduce its core symptoms, as well as
      associated depression and disability. The findings of this review support the
      status of SSRIs as first line agents in the pharmacotherapy of PTSD, as well as
      their value in long-term treatment. However, there remain important gaps in the
      evidence base, and a continued need for more effective agents in the management
      of PTSD.

PMID- 16437446
TI  - Intra-articular steroids and splints/rest for children with juvenile idiopathic
      arthritis and adults with rheumatoid arthritis.
AB  - BACKGROUND: Resting or immobilizing a joint to enhance outcomes following intra
      articular (IA) steroid injection is generally advocated. This systematic review
      aimed to determine the efficacy of IA steroid injections and the influence of
      post-injection rest. OBJECTIVES: 1. Compare IA steroid injections versus no
      treatment or placebo. 2. Determine the effects of rest following IA steroid
      injection in rheumatoid or juvenile idiopathic arthritis. SEARCH STRATEGY: The
      Cochrane Central Register of Controlled Trials (CENTRAL- Issue 4, 2003), Cochrane
      Database of Systematic Reviews (CDSR - Issue 4, 2003), Database of Abstracts of
      Reviews of Effectiveness (DARE - searched 8.1.04), MEDLINE (1966 to August Week 2
      2004), EMBASE (1980 to August Week 2 2004) , CINAHL (1982 to December Week 2
      2003), Clinical Trials site of the National Institute of Health, (USA - searched
      8.1.04), OTseeker (Occupational Therapy Systematic Evaluation of Evidence -
      searched 8.1.04) and PEDro (Physiotherapy Evidence Database - searched 8.1.04)
      were searched. Journals and reference lists were hand searched. SELECTION
      CRITERIA: Eligible were randomised controlled trials of IA steroid injections or
      of rest following IA steroid injections in rheumatoid or juvenile idiopathic
      arthritis. DATA COLLECTION AND ANALYSIS: Potentially relevant references were
      evaluated and all data extracted by two independent reviewers. MAIN RESULTS: Five
      trials (n=346) examining IA steroid injection in the knee joint were included. It
      was not possible to pool data as outcome measures, timing of follow up and the
      methods of data reporting differed between trials. There was inconclusive
      conflicting evidence from two trials that walking time was reduced. There was
      evidence from one moderate quality trial that pain was reduced at 1-day post
      injection (0-100 VAS from 28.33 to 13.46; McGill Pain Scale from 8.89 to 3.96)
      but not at 1 week or 7-12 weeks post-injection. There is some evidence that IA
      injections improved knee flexion (by 14 degrees) and reduced knee extension lag
      (by 20 degrees), knee circumference (median reduction = 0.3 cm) and morning
      stiffness (reduced from 60 mins to 7.6 mins). One trial (n=91) examined the
      effects of rest following injection in the knee. The rested group achieved
      significant improvement in pain, stiffness, knee circumference, and walking time
      when compared with the non-rested group (no point estimates provided). One trial
      evaluated rest following injection of the wrist (n=117). Relapse rate was higher
      in the rested group (rest relapse rate = 24/58, no-rest group = 14/59); but there
      were no differences between the rested and non-rested groups on pain, joint
      circumference, wrist function, grip strength or ROM. AUTHORS' CONCLUSIONS: There
      is some evidence to support the use of IA steroid injections and resting a knee
      following injections but that wrists should not be rested following injections.
      The included studies involved adult participants so any conclusions can only
      cautiously applied to children. Further research is required to examine the use
      and type of rest and the differential responses of different joints following
      injections.

PMID- 16437447
TI  - Oral xanthines as maintenance treatment for asthma in children.
AB  - BACKGROUND: Xanthines have been used in the treatment of asthma as a
      bronchodilator, though they may also have anti-inflammatory effects. The current
      role of xanthines in the long-term treatment of childhood asthma needs to be
      reassessed. OBJECTIVES: To determine the efficacy of xanthines (e.g.
      theophylline) in the maintenance treatment of paediatric asthma. SEARCH STRATEGY:
      A search of the Cochrane Airways Group Specialised Register was undertaken with
      predefined search terms. Searches are current to May 2005. SELECTION CRITERIA:
      Randomised controlled trials,lasting at least four weeks comparing a xanthine
      with placebo, regular short-acting beta-agonist (SABA), inhaled corticosteroids
      (ICS), cromoglycate (SCG), ketotifen (KET) or leukotriene antagonist, in children
      with diagnosed with chronic asthma between 18 months and 18 years old. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected each study for
      inclusion in the review and extracted data. Primary outcome was percentage of
      symptom-free days. MAIN RESULTS: Thirty-four studies (2734 participants) of
      adequate quality were included. Xanthine versus placebo (17 studies): The
      proportion of symptom free days was larger with xanthine compared with placebo
      (7.97% [95% CI 3.41, 12.53]). Rescue medication usage was lower with xanthine,
      with no significant difference in symptom scores or hospitalisations. FEV1 , and
      PEF were better with xanthine. Xanthine was associated with non - specific side
      effects. Data from behavioural scores were inconclusive. Xanthine versus ICS
      (four studies) : Exacerbations were less frequent with ICS, but no significant
      difference on lung function was observed. Individual studies reported significant
      improvements in symptom measures in favour of steroids, and one study reported a
      difference in growth rate in favour of xanthine. No difference was observed for
      study withdrawal or tremor. Xanthine was associated with more frequent headache
      and nausea. Xanthine versus regular SABA (10 studies): No significant difference
      in symptoms, rescue medication usage and spirometry. Individual studies reported
      improvement in PEF with beta-agonist. Beta-agonist treatment led to fewer
      hospitalisations and headaches. Xanthine was associated with less tremor.
      Xanthine versus SCG (six studies ): No significant difference in symptoms,
      exacerbations and rescue medication. Sodium cromoglycate was associated with
      fewer gastro-intestinal side-effects than xanthine. Xanthine versus KET (one
      study): No statistical tests of significance between xanthine and ketotifen were
      reported. Xanthine + ICS versus placebo + same dose ICS (three studies) : Results
      were conflicting due to clinical/methodological differences, and could not be
      aggregated. AUTHORS' CONCLUSIONS: Xanthines as first-line preventer alleviate
      symptoms and reduce requirement for rescue medication in children with mild to
      moderate asthma. When compared with ICS they were less effective in preventing
      exacerbations. Xanthines had similar efficacy as single preventative agent
      compared with regular SABA and SCG. Evidence on AEs (adverse effects) was
      equivocal: there was evidence for increased AEs overall, but no evidence that any
      specific AE (including effects on behaviour and attention) occurred more
      frequently than with placebo. There is insufficient evidence from available
      studies to make firm conclusions about the effectiveness of xanthines as add-on
      preventative treatment to ICS, and there are no published paediatric studies
      comparing xanthines with alternatives in this role. Our data suggest that
      xanthines are only suitable as first-line preventative asthma therapy in children
      when ICS are not available. They may have a role as add-on therapy in more severe
      asthma not controlled by ICS, but further studies are needed to examine this, and
      to define the risk-benefit ratio compared with other agents.

PMID- 16437448
TI  - Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes
      mellitus.
AB  - BACKGROUND: Metformin is an oral anti-hyperglycemic agent used in the treatment
      of type 2 diabetes mellitus. The results of the UK Prospective Diabetes Study
      indicate that metformin treatment is associated with a reduction in total
      mortality compared to other anti-hyperglycemic treatments. Metformin, however, is
      thought to increase the risk of lactic acidosis, and is considered to be
      contraindicated in many chronic hypoxemic conditions that may be associated with
      lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease,
      and advancing age. OBJECTIVES: To assess the incidence of fatal and nonfatal
      lactic acidosis with metformin use compared to placebo and other glucose-lowering
      treatments in patients with type 2 diabetes mellitus. A secondary objective was
      to evaluate the blood lactate levels for those on metformin treatment compared to
      placebo or non-metformin therapies. SEARCH STRATEGY: A search was performed of
      The Cochrane Library (up to 8/2005), MEDLINE (up to 8/2005), EMBASE (up to
      11/2000), OLD MEDLINE, and REACTIONS (up to 8/2005), in order to identify all
      studies of metformin treatment from 1966 to August 2005. The Cumulated Index
      Medicus was used to search relevant articles from 1959 to 1965. The search was
      augmented by scanning references of identified articles, and by contacting
      principal investigators. Date of latest search: August 2005. SELECTION CRITERIA:
      Prospective trials in patients with type 2 diabetes that lasted longer than one
      month were included if they evaluated metformin, alone or in combination with
      other treatments, compared to placebo or any other glucose-lowering therapy.
      Observational cohort studies of metformin treatment lasting greater than one
      month were also included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials to be included, assessed study quality and
      extracted data. The incidence of fatal and nonfatal lactic acidosis was recorded
      as cases per patient-years, for metformin treatment and for placebo or other
      treatments. The upper limit for the true incidence of cases in the metformin and
      non-metformin groups were calculated using Poisson statistics. In a second
      analysis lactate levels were measured as a net change from baseline or as mean
      treatment values (basal and stimulated by food or exercise) for treatment and
      comparison groups. The pooled results were recorded as a weighted mean difference
      (WMD) in mmol/L, using the fixed effect model for continuous data. MAIN RESULTS:
      Pooled data from 206 comparative trials and cohort studies revealed no cases of
      fatal or nonfatal lactic acidosis in 47,846 patient-years of metformin use or in
      38,221 patients-years in the non-metformin group. Using Poisson statistics with
      95% confidence intervals the upper limit for the true incidence of metformin
      associated lactic acidosis was 6.3 cases per 100,000 patient-years, and the upper
      limit for the true incidence of lactic acidosis in the non-metformin group was
      7.8 cases per 100,000 patient-years. There was no difference in lactate levels,
      either as mean treatment levels or as a net change from baseline, for metformin
      compared to placebo or other non-biguanide therapies. The mean lactate levels
      were slightly lower for metformin treatment compared to phenformin (WMD -0.75
      mmol/L, 95% CI -0.86 to -0.15). AUTHORS' CONCLUSIONS: There is no evidence from
      prospective comparative trials or from observational cohort studies that
      metformin is associated with an increased risk of lactic acidosis, or with
      increased levels of lactate, compared to other anti-hyperglycemic treatments if
      prescribed under the study conditions.

PMID- 16437449
TI  - Psychological interventions for adults with asthma.
AB  - BACKGROUND: Many people have asthma, and for some their symptoms may be triggered
      by psychological factors. In addition compliance with medical therapy may have a
      psychological dimension. Therefore, psychological interventions aim to reduce the
      burden of symptoms and improve management of the disease. OBJECTIVES: To assess
      the effectiveness of psychological interventions for adults with asthma. SEARCH
      STRATEGY: The Cochrane Airways Group Specialised Register and PsycINFO were
      searched with pre-defined terms up until August 2005. SELECTION CRITERIA:
      Randomised controlled trials published in any language assessing the effects of a
      psychological intervention compared with a form of control in adult participants
      were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers assessed
      the relevance of abstracts identified by electronic searching and retrieved
      agreed studies for further scrutiny. The studies that met the inclusion criteria
      were assembled and data extracted. MAIN RESULTS: Fourteen studies, involving 617
      particpants, were included in the review, however study quality was poor and
      sample sizes were frequently small. However, some pooled effects were analysed.
      The use of 'as needed' medications was reduced in two studies, (47 patients), by
      relaxation therapy (OR 4.47, CI 1.22 to 16.44). There was no significant
      difference in FEV1 for relaxation therapy in four studies of 150 patients, (SMD 
      0.01, CI -0.41 to 0.40). Quality of life, measured using the Asthma Quality of
      Life Questionnaire in two studies, (48 patients), showed a positive effect
      following CBT (WMD 0.71, CI 0.23 to 1.19). Peak Expiratory Flow outcome data in
      two studies, (51 patients), indicated a significant difference in favour of bio
      feedback therapy (SMD 0.66, CI 0.09 to 1.23). The remainder of the findings
      between studies were conflicting. This may have been due to the different types
      of interventions used and the deficiencies in trial design. AUTHORS' CONCLUSIONS:
      This review was unable to draw firm conclusions for the role of psychological
      interventions in asthma due to the absence of an adequate evidence base. Larger,
      well-conducted and reported randomised trials are required in this area, in order
      to determine the effects of these techniques in the treatment of asthma in
      adults.

PMID- 16437450
TI  - Horse chestnut seed extract for chronic venous insufficiency.
AB  - BACKGROUND: Conservative therapy of chronic venous insufficiency (CVI) consists
      largely of compression treatment. However, this often causes discomfort and has
      been associated with poor compliance. Therefore, oral drug treatment is an
      attractive option. OBJECTIVES: To review the efficacy and safety of oral horse
      chestnut seed extract (HCSE) versus placebo, or reference therapy, for the
      treatment of CVI. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular
      Diseases Review Group's Specialised Register (October 2005), the Cochrane Central
      Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005,
      MEDLINE (January 1966 to October 2005), EMBASE (January 1980 to October 2005),
      Allied and Complementary Medicine (AMED) (inception to July 2005) and Phytobase
      (inception to January 2001) for randomised controlled trials (RCTs) of HCSE for
      chronic venous insufficiency. Manufacturers of HCSE preparations and experts on
      the subject were contacted for published and unpublished material. There were no
      restrictions on language. SELECTION CRITERIA: RCTs were included if they compared
      oral HCSE mono-preparations with placebo, or reference therapy, in people with
      CVI. Trials assessing HCSE as one of several active components in a combination
      preparation, or as a part of a combination treatment, were excluded. DATA
      COLLECTION AND ANALYSIS: Both authors independently selected the studies and,
      using a standard scoring system, assessed methodological quality and extracted
      data. Disagreements concerning evaluation of individual trials were resolved
      through discussion. MAIN RESULTS: Overall, there appeared to be an improvement in
      CVI related signs and symptoms with HCSE compared with placebo. Leg pain was
      assessed in seven placebo-controlled trials. Six reported a significant reduction
      of leg pain in the HCSE groups compared with the placebo groups, while another
      reported a statistically significant improvement compared with baseline. One
      trial suggested a weighted mean difference (WMD) of 42.4 mm (95% confidence
      interval (CI) 34.9 to 49.9) measured on a 100 mm visual analogue scale. Leg
      volume was assessed in seven placebo-controlled trials. Meta-analysis of six
      trials (n = 502) suggested a WMD of 32.1ml (95% CI 13.49 to 50.72) in favour of
      HCSE compared with placebo. One trial indicated that HCSE may be as effective as
      treatment with compression stockings. Adverse events were usually mild and
      infrequent. AUTHORS' CONCLUSIONS: The evidence presented implies that HCSE is an
      efficacious and safe short-term treatment for CVI. However, several caveats exist
      and more rigorous RCTs are required to confirm the efficacy of this treatment
      option.

PMID- 16437451
TI  - Interventions for vitiligo.
AB  - BACKGROUND: Around 1% of the world's population has vitiligo, which causes a loss
      of skin colour in patches. The methods currently available to treat vitiligo are
      largely unsatisfactory and vary widely between cultures and within health
      systems. OBJECTIVES: To assess the effects of interventions used to manage
      vitiligo. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised
      Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE,
      AMED and other databases (last searched September 2004). Reference lists of
      articles and conference proceedings were searched. Authors of reviews were
      contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA
      COLLECTION AND ANALYSIS: At least two reviewers independently assessed study
      eligibility and methodological quality and carried out data extraction. The
      included studies compared different interventions and used different outcome
      measures so we considered it inappropriate to combine their results. MAIN
      RESULTS: Nineteen trials with a total of 1350 participants were included. The
      RCTs generally had low numbers of participants and only RCTs of repigmentation
      and not other methods of managing vitiligo were able to be included. In one
      study, potent topical steroids resulted in better repigmentation than placebo and
      they were also better than oral psoralens plus sunlight in another study (RR 4.70
      95% CI 1.14 to 19.39) although their long-term use is limited by adverse effects.
      Two studies suggested that topical calcipotriol enhanced repigmentation rates
      from PUVAsol and PUVA when compared with placebo. Another two studies showed
      higher repigmentation rates with oral PUVAsol versus placebo plus sunlight (RR
      19.20 95% CI 1.21 to 304.50 in 79 adults and RR 2.29 95% CI 1.14 to 4.58 in a
      study of 50 children). The safety of these interventions was poorly described and
      none of the studies was able to demonstrate long term benefits. Very few studies
      were carried out on children or included segmental vitiligo. No trials evaluating
      micropigmentation, melanocyte transplantation, depigmentation or cosmetic
      camouflage could be found. Despite the fact that the main impact of vitiligo is
      psychosocial only one study on psychological therapy was found and it is awaiting
      assessment. AUTHORS' CONCLUSIONS: This review has found some evidence to support
      existing therapies for vitiligo, but the different designs and outcome
      measurements, lack of quality of life measures and adverse effect reporting in
      the studies limit the usefulness of their findings. There is a pressing need for
      high quality randomised trials using standardised measures of repigmentation and
      which address relevant clinical outcomes including quality of life.

PMID- 16437452
TI  - Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic
      combination therapy for sepsis.
AB  - BACKGROUND: Optimal antibiotic treatment for sepsis is imperative. Combining a
      beta-lactam antibiotic with an aminoglycoside antibiotic may have certain
      advantages over beta-lactam monotherapy. OBJECTIVES: We compared clinical
      outcomes for beta lactam-aminoglycoside combination therapy versus beta lactam
      monotherapy for sepsis. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3, 2004);
      MEDLINE (1966 to July 2004); EMBASE (1980 to March 2003); LILACS (1982 to July
      2004); and conference proceedings of the Interscience Conference of Antimicrobial
      Agents and Chemotherapy (1995 to 2003). We scanned citations of all identified
      studies and contacted all corresponding authors. SELECTION CRITERIA: We included
      randomized and quasi-randomized trials comparing any beta-lactam monotherapy to
      any combination of one beta-lactam and one aminoglycoside for sepsis. DATA
      COLLECTION AND ANALYSIS: The primary outcome was all-cause fatality. Secondary
      outcomes included treatment failure, superinfections, colonization, and adverse
      events. Two authors independently collected data. We pooled relative risks (RR)
      with their 95% confidence intervals (CI) using the fixed effect model. We
      extracted outcomes by intention-to-treat analysis whenever possible. MAIN
      RESULTS: We included 64 trials, randomizing 7586 patients. Twenty trials compared
      the same beta-lactam in both study arms, while the remaining compared different
      beta-lactams using a broader spectrum beta-lactam in the monotherapy arm. In
      studies comparing the same beta-lactam, we observed no difference between study
      groups with regard to all-cause fatality, RR 1.01 (95% CI 0.75-1.35) and clinical
      failure, RR 1.11 (95% CI 0.95-1.29). In studies comparing different beta-lactams,
      we observed an advantage to monotherapy: all cause fatality RR 0.85 (95% CI 0.71
      1.01), clinical failure RR 0.77 (95% CI 0.69-0.86). No significant disparities
      emerged from subgroup and sensitivity analyses, including the assessment of
      patients with Gram-negative and Pseudomonas aeruginosa infections. We detected no
      differences in the rate of resistance development. Adverse events rates did not
      differ significantly between the study groups overall, although nephrotoxicity
      was significantly more frequent with combination therapy, RR 0.30 (95% CI 0.23
      0.39). We found no heterogeneity for all comparisons. We included a small subset
      of studies addressing patients with Gram-positive infections, mainly
      endocarditis. We identified no difference between monotherapy and combination
      therapy in these studies. AUTHORS' CONCLUSIONS: The addition of an aminoglycoside
      to beta-lactams for sepsis should be discouraged. All-cause fatality rates are
      unchanged. Combination treatment carries a significant risk of nephrotoxicity.

PMID- 16437453
TI  - Topiramate for acute affective episodes in bipolar disorder.
AB  - BACKGROUND: Bipolar disorder is a common recurrent illness with high levels of
      chronicity. Treatment resistance persists despite the use of established
      medications, such as lithium and valproate. New medications are required for the
      treatment of refractory cases. Retrospective and open-label trials have suggested
      that the anticonvulsant topiramate may be efficacious in bipolar disorder. There
      is a need to clarify the evidence available in the form of randomised controlled
      trials for its use in bipolar disorder. OBJECTIVES: To review the evidence for
      the efficacy and acceptability of topiramate in the treatment of acute mood
      episodes in bipolar disorder. SEARCH STRATEGY: The Cochrane Collaboration
      Depression, Anxiety and Neurosis (CCDAN) group search strategy was used. The
      following databases were searched:The Cochrane Collaboration Depression, Anxiety
      and Neurosis Controlled Trials Register (CCDANCTR), September 2003;The Cochrane
      Controlled Clinical Trials Register (CCCTR), September 2003;EMBASE (1980 to
      December 2003);MEDLINE (1966 to December 2003);LILACS;PsycLIT;Psyndex.Reference
      lists of relevant papers and major textbooks of mood disorder. Handsearches
      (specialist journals and conference proceedings). Authors, other experts in the
      field and pharmaceutical companies were contacted for knowledge of suitable
      published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials
      which compared topiramate with placebo or with active agents in the treatment of
      any acute mood episodes in bipolar disorder. Participants were patients with
      bipolar disorder and were males and females of all ages. DATA COLLECTION AND
      ANALYSIS: Data extraction and methodological quality assessment were performed
      independently by two reviewers. For analysis, relative risk was used for binary
      efficacy outcomes and the weighted mean difference or standardised mean
      difference was used for continuously distributed outcomes. MAIN RESULTS: One
      randomised controlled trial met the inclusion criteria for the review, a
      comparison between topiramate and bupropion sustained release (SR) in the
      adjunctive treatment of depressed patients with bipolar disorder. However, the
      trial had several limitations in methodology and in the description of data. Its
      data regarding efficacy required clarification before it could be analysed
      according to the protocol of this systematic review. From the limited data
      available, topiramate had efficacy similar to bupropion SR in the adjunctive
      treatment of bipolar depression. Both groups of subjects suffered a high drop-out
      rate. There was no significant difference between the topiramate and the
      bupropion treated groups in those dropping out for any reason (relative risk
      1.60, 95% confidence interval 0.65 to 3.96). There was no significant difference
      in those withdrawing from the study due to adverse effects (relative risk 1.50,
      95% confidence interval 0.51 to 4.43). Although the data on weight loss were not
      analysed formally, weight loss was marked in the topiramate treated group.
      Several unpublished trials have been identified and data from these trials may be
      included in future reviews. AUTHORS' CONCLUSIONS: There is insufficient evidence
      on which to base any recommendations regarding the use of topiramate in any phase
      of bipolar illness, either in monotherapy or as an adjunctive treatment.

PMID- 16437454
TI  - Interventions for treating brain arteriovenous malformations in adults.
AB  - BACKGROUND: Brain arteriovenous malformations (AVMs) are the single most common
      cause of intracerebral haemorrhage in young adults. Brain AVMs also cause
      seizure(s) and focal neurological deficits (in the absence of haemorrhage,
      migraine or an epileptic seizure); approximately one fifth are incidental
      discoveries. Various interventions are used in an attempt to eradicate brain
      AVMs: neurosurgical excision, stereotactic radiotherapy/'radiosurgery' (using
      gamma knife, linear accelerator or proton beam), endovascular embolisation (using
      glues, particles, fibres, coils, or balloons), and staged combinations of these
      interventions. OBJECTIVES: To assess the clinical effects of interventions to
      treat brain AVMs in adults (with the aim of either partial obliteration or total
      eradication), using data published in randomised controlled trials. SEARCH
      STRATEGY: We searched: (1) the Cochrane Stroke Group Register (last searched
      December 2004); (2) medical literature databases (MEDLINE 1966 to 31 December
      2004 and EMBASE 1980 to 31 December 2004); (3) on-line and paper journal
      surveillance; (4) the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library Issue 1, 2005); (5) international registers of clinical
      trials; (6) bibliographies of relevant articles identified by (1) to (5); and (7)
      we sought unpublished data from manufacturers of interventional treatments for
      brain AVMs. SELECTION CRITERIA: We sought randomised trials of any or all of the
      interventions for brain AVMs, compared against each other or against usual
      medical therapy, with relevant clinical outcome measures. DATA COLLECTION AND
      ANALYSIS: Two authors independently applied the inclusion criteria and reviewed
      the relevant studies. MAIN RESULTS: We did not find any randomised trials meeting
      our selection criteria. We found two randomised trials which tested the
      equivalence of two embolic agents for the pre-operative embolisation of brain
      AVMs (one published, one unpublished), but none of the primary or secondary
      outcome measures in these trials met our desired criteria; although important
      clinical outcomes were reported, meaningful comparison of the two treatment arms
      was impossible. We also excluded a third RCT which studied three different blood
      pressure lowering treatments to induce deliberate hypotension during surgical
      resection of brain AVMs, because the intervention was not the focus of this
      review. AUTHORS' CONCLUSIONS: There is no evidence from randomised trials with
      clear clinical outcomes, comparing different interventional treatments for brain
      AVMs against each other or against usual medical therapy, to guide the
      interventional treatment of brain AVMs in adults. One such trial (ARUBA),
      comparing interventional versus conservative management for unruptured brain
      AVMs, is being planned.

PMID- 16437455
TI  - The effectiveness of atypical antipsychotics for the treatment of aggression and
      psychosis in Alzheimer's disease.
AB  - BACKGROUND: Aggression, agitation or psychosis occur in the majority of people
      with dementia at some point in the illness. There have been a number of trials of
      atypical antipsychotics to treat these symptoms over the last five years, and a
      systematic review is needed to evaluate the evidence in a balanced way.
      OBJECTIVES: To determine whether evidence supports the use of atypical
      antipsychotics for the treatment of aggression, agitation and psychosis in people
      with Alzheimer's disease. SEARCH STRATEGY: The trials were identified from a last
      updated search of the Specialized Register of the Cochrane Dementia and Cognitive
      Improvement Group on 7 December 2004 using the terms olanzapine, quetiapine,
      risperidone, clozapine, amisulpride, sertindole, zotepine, aripiprazole,
      ziprasidone. This Register contains articles from all major healthcare databases
      and many ongoing trials databases and is updated regularly. SELECTION CRITERIA:
      Randomised, placebo-controlled trials, with concealed allocation, where dementia
      and psychosis and/or aggression were assessed. DATA COLLECTION AND ANALYSIS: 1.
      Two reviewers extracted data from included trials2. Data were pooled where
      possible, and analysed using appropriate statistical methods3. Analysis included
      patients treated with an atypical antipsychotic, compared with placebo MAIN
      RESULTS: Sixteen placebo controlled trials have been completed with atypical
      antipsychotics although only nine had sufficient data to contribute to a meta
      analysis and only five have been published in full in peer reviewed journals. No
      trials of amisulpiride, sertindole or zotepine were identified which met the
      criteria for inclusion. The included trials led to the following results:1. There
      was a significant improvement in aggression with risperidone and olanzapine
      treatment compared to placebo.2. There was a significant improvement in psychosis
      amongst risperidone treated patients.3. Risperidone and olanzpaine treated
      patients had a significantly higher incidence of serious adverse cerebrovascular
      events (including stroke), extra-pyramidal side effects and other important
      adverse outcomes.4. There was a significant increase in drop-outs in risperidone
      (2 mg) and olanzapine (5-10 mg) treated patients.5. The data were insufficient to
      examine impact upon cognitive function. AUTHORS' CONCLUSIONS: Evidence suggests
      that risperidone and olanzapine are useful in reducing aggression and risperidone
      reduces psychosis, but both are associated with serious adverse cerebrovascular
      events and extra-pyramidal symptoms. Despite the modest efficacy, the significant
      increase in adverse events confirms that neither risperidone nor olanzapine
      should be used routinely to treat dementia patients with aggression or psychosis
      unless there is marked risk or severe distress. Although insufficient data were
      available from the considered trials, a meta-analysis of seventeen placebo
      controlled trials of atypical neuroleptics for the treatment of behavioural
      symptoms in people with dementia conducted by the Food and Drug Administration
      (using data not in the public domain) suggested a significant increase in
      mortality (OR 1.7).

PMID- 16437456
TI  - Antidepressants for depressed elderly.
AB  - BACKGROUND: Depression is a relatively common experience in older adults. The
      syndrome is associated with considerable distress, morbidity and service
      commitment. Approximately two thirds of patients presenting with severe forms
      will respond to antidepressant treatment and the last twenty years has witnessed
      a great increase in the number of these drugs. Older, frail people are
      particularly vulnerable to side effects. OBJECTIVES: The aims of this review were
      to examine the efficacy of antidepressant classes, to compare the withdrawal
      rates associated with each class and describe the side effect profile of
      antidepressant drugs for treating depression in patients described as elderly,
      geriatric, senile or older adults, aged 55 or over. SEARCH STRATEGY: The Cochrane
      Collaboration Depression, Anxiety and Neurosis Controlled Trials Register
      (CCDANCTR-Studies) was searched (2003-08-13). Reference lists of relevant papers
      and previous systematic reviews were hand searched for published reports and
      citations of unpublished studies. SELECTION CRITERIA: Only randomised controlled
      trials were included. Trials had to compare at least two active antidepressant
      drugs in the treatment of depression. DATA COLLECTION AND ANALYSIS: Reviewers
      extracted data independently. In examining efficacy, the reviewers assumed that
      people who died or dropped out had no improvement. Withdrawal rates irrespective
      of cause and specifically due to side effects were compared between drug classes.
      Relative risk (RR) for dichotomous data and weighted mean difference for
      continuous data were calculated with 95% confidence intervals (CI). Qualitative
      side effect data were reported in terms of ratios of side effects and percentage
      of patients experiencing specific side effects. MAIN RESULTS: A total of 29
      trials provided data for inclusion in the review. We were unable to find any
      differences in efficacy when comparing classes of antidepressants. However, as
      the trials contained relatively small numbers of patients, these findings may be
      explained by a type two error. Tricyclic antidepressants (TCAs) compared less
      favourably with selective serotonin reuptake inhibitors (SSRIs) in terms of
      numbers of patients withdrawn irrespective of reason (RR: 1.24, CI 1.04, 1.47)
      and number withdrawn due to side effects (RR: 1.30, CI 1.02, 1.64). Subgroup
      analyses demonstrated that TCA related antidepressants had similar withdrawal
      rates to SSRIs irrespective of reason of withdrawal (RR: 1.49, CI 0.74, 2.98) or
      withdrawal due to side effects (RR: 1.07, CI 0.43, 2.70). The qualitative
      analysis of side effects showed a small increased profile of gastro-intestinal
      and neuropsychiatric side effects associated with classical TCAs. AUTHORS'
      CONCLUSIONS: Our findings suggest that SSRIs and TCAs are of the same efficacy.
      However, we have found some evidence suggesting that TCA related antidepressants
      and classical TCAs may have different side effect profiles and are associated
      with differing withdrawal rates when compared with SSRIs. The review suggests
      that classical TCAs are associated with a higher withdrawal rate due to side
      effect experience, although these results must be interpreted with caution due to
      the relatively small size of the review and the heterogeneity of the drugs and
      patient populations.

PMID- 16437457
TI  - Cotrimoxazole prophylaxis for opportunistic infections in children with HIV
      infection.
AB  - BACKGROUND: The majority of children with HIV infection live in low-income
      countries without access to antiretroviral drugs. The prevention and early
      treatment of opportunistic infections are the mainstay of their medical
      management. Cotrimoxazole is cheap and effective against a wide range of
      organisms, including Pneumocystis jiroveci pneumonia (PCP), which is an important
      cause of death and illness in the first year of life. It is safe with relatively
      few side effects. Diagnosis of HIV in children is complicated by the presence of
      maternal antibodies in early life. Providing prophylaxis based initially on
      maternal status is one possible solution. However, routine prophylactic treatment
      is difficult to deliver in low-resource settings, and could also lead to
      increased resistance to the drug. OBJECTIVES: To assess the effects of routinely
      administered cotrimoxazole on death and illness episodes in children with HIV
      infection, and in infants of HIV-infected mothers. SEARCH STRATEGY: We searched
      the Cochrane HIV/AIDS registry, MEDLINE, the Cochrane Controlled Trials Register,
      LILACS, AIDSLINE, AIDSTRIALS and AIDSDRUGS databases, and proceedings and
      abstracts from AIDS and TB conferences (search date Feb 2005). We checked
      reference lists of pertinent articles, and contacted pharmaceutical companies and
      experts in the field. SELECTION CRITERIA: Randomised or quasi-randomised trials
      comparing routinely administered cotrimoxazole versus placebo or no treatment in
      children (age less than 15 years) with HIV infection, or children less than 18
      months with HIV infected mothers. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial eligibility and quality. Where data were incomplete
      or unclear trial authors were contacted for further details. MAIN RESULTS: One
      study was identified that fulfilled the inclusion criteria. It studied 534
      children with HIV infection in Lusaka, Zambia. The study was conducted in an area
      of high bacterial resistance to cotrimoxazole (60-80%). A reduction in mortality
      of 33% was seen in the cotrimoxazole group as compared to placebo, relative risk
      0.67 (95% CI 0.53 - 0.85). There was also a beneficial effect on hospitalisation,
      relative risk 0.77 (95% CI 0.62 - 0.96). There was no difference in adverse
      events between groups, and the beneficial effect was seen across all ages and
      CD4%. AUTHORS' CONCLUSIONS: A single trial has shown a beneficial effect from the
      use of cotrimoxazole prophylaxis in HIV infected children in Zambia. It must be
      decided whether this can be extrapolated to other resource-poor settings.

PMID- 16437458
TI  - Effects of interventions aimed at changing the length of primary care physicians'
      consultation.
AB  - BACKGROUND: Observational studies have shown differences in process and outcome
      between the consultations of primary care physicians whose average consultation
      lengths differ. These differences may be due to self selection. OBJECTIVES: To
      assess the effectiveness and efficiency of interventions to alter the length of
      primary care physicians' consultations. SEARCH STRATEGY: The following electronic
      databases were searched: Cochrane Effective Practice and Organisation of Care
      Group (EPOC) Specialised Register (October 2002); CENTRAL (The Cochrane Library
      June 2003); MEDLINE (1966 to October 2002);EMBASE (1981 to October 2002); NHS
      National Research Register (June 2003). The search strategies combined subject
      terms for 'general practice', 'consultation' and 'length' with methodological
      filters. SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled
      clinical trials (CCTs) of interventions to alter the length of primary care
      physicians' consultations. DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by two authors using agreed criteria. Disagreements were resolved
      by discussion. Where data were missing attempts were made to contact authors.
      Given the heterogeneity of studies meta-analysis was not attempted, and results
      are presented as a narrative summary. MAIN RESULTS: Six articles describing four
      UK trials met the inclusion criteria. All tested short term changes in the
      consultation time allocated to each patient and all had methodological
      weaknesses, particularly due to non-random allocation of patients. Altering
      appointment length resulted in modest changes in average length of consultation.
      There were no consistent differences in problem recognition, examination,
      prescribing, referral or investigation rates. There was some evidence that blood
      pressure was checked and smoking discussed more often when more time was
      available. None of the interventions were associated with differences in patient
      satisfaction. No trials examined efficiency. AUTHORS' CONCLUSIONS: The findings
      of this review do not provide sufficient evidence to support or resist a policy
      of altering the lengths of primary care physicians' consultations. Further trials
      are needed that focus on health outcomes and cost effectiveness.

PMID- 16437459
TI  - Non-latex versus latex male condoms for contraception.
AB  - BACKGROUND: The male condom, which consists of a thin sheath placed over the
      glans and shaft of the penis, is designed to prevent pregnancy by providing a
      physical barrier against the deposition of semen into the vagina during
      intercourse. Beginning in the 1990s, nonlatex male condoms made of polyurethane
      film or synthetic elastomers were developed as alternative male barrier methods
      for individuals with allergies, sensitivities or preferences that prevented the
      consistent use of condoms made of latex. OBJECTIVES: The review sought to
      evaluate nonlatex male condoms in comparison with latex condoms in terms of
      contraceptive efficacy, breakage and slippage, safety, and user preferences.
      SEARCH STRATEGY: We searched computerized databases for randomized controlled
      trials of nonlatex condoms. We also wrote to the manufacturers of nonlatex
      condoms and known investigators in an attempt to locate any other trials not
      identified in our search. SELECTION CRITERIA: The review included all randomized
      controlled trials identified in the literature search that evaluated a male
      nonlatex condom made of polyurethane film or synthetic elastomers in comparison
      with a latex condom. DATA COLLECTION AND ANALYSIS: We evaluated all titles and
      abstracts located in the literature searches for inclusion. Two authors
      independently extracted data from the identified studies. We analyzed data with
      RevMan. The Peto odds ratio (Peto OR) with 95% confidence interval (CI) was
      calculated for each outcome of contraceptive efficacy, condom breakage and
      slippage, discontinuation of use, safety, and user preference. Contraceptive
      efficacy, early discontinuation, and safety outcomes were also measured with
      survival analysis techniques. MAIN RESULTS: While the eZ.on condom did not
      protect against pregnancy as well as its latex comparison condom, no differences
      were found in the typical-use efficacy between the Avanti and the Standard
      Tactylon and their latex counterparts. The nonlatex condoms had significantly
      higher rates of clinical breakage than their latex comparison condoms: the Peto
      OR for clinical breakage ranged from 2.6 (95% CI 1.6 to 4.3) to 5.0 (95% CI 3.6
      to 6.8). Few adverse events were reported. Substantial proportions of
      participants preferred the nonlatex condom or reported that they would recommend
      its use to others. AUTHORS' CONCLUSIONS: Although the nonlatex condoms were
      associated with higher rates of clinical breakage than their latex comparison
      condoms, the new condoms still provide an acceptable alternative for those with
      allergies, sensitivities, or preferences that might prevent the consistent use of
      latex condoms. The contraceptive efficacy of the nonlatex condoms requires more
      research.

PMID- 16437460
TI  - Interventions for replacing missing teeth: bone augmentation techniques for
      dental implant treatment.
AB  - BACKGROUND: Dental implants require sufficient bone to be adequately stabilised.
      For some patients implant treatment would not be an option without bone
      augmentation. A variety of materials and surgical techniques are available for
      bone augmentation. OBJECTIVES: General objectives: To test the null hypothesis of
      no difference in the success, function, morbidity and patient satisfaction
      between different bone augmentation techniques for dental implant treatment.
      SPECIFIC OBJECTIVES: (A) to test whether and when augmentation procedures are
      necessary; (B) to test which is the most effective augmentation technique for
      specific clinical indications. Trials were divided into three broad categories
      according to different indications for the bone augmentation techniques: (1)
      major vertical or horizontal bone augmentation or both; (2) implants placed in
      extraction sockets; (3) fenestrated implants. SEARCH STRATEGY: The Cochrane Oral
      Health Group's Trials Register, the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE and EMBASE were searched. Several dental journals were
      handsearched. The bibliographies of review articles were checked, and personal
      references were searched. More than 55 implant manufacturing companies were also
      contacted. Last electronic search was conducted on 1 October 2005. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) of different techniques and
      materials for augmenting bone for implant treatment reporting the outcome of
      implant therapy at least to abutment connection. DATA COLLECTION AND ANALYSIS:
      Screening of eligible studies, assessment of the methodological quality of the
      trials and data extraction were conducted independently and in duplicate. Authors
      were contacted for any missing information. Results were expressed as random
      effects models using weighted mean differences for continuous outcomes and odd
      ratios for dichotomous outcomes with 95% confidence intervals. The statistical
      unit of the analysis was the patient. MAIN RESULTS: Thirteen RCTs out of 29
      potentially eligible trials reporting the outcome of 330 patients were suitable
      for inclusion. Since different techniques were evaluated in different trials, no
      meta-analysis could be performed. Six trials evaluated different techniques for
      vertical or horizontal bone augmentation or both. Four trials evaluated different
      techniques of bone grafting for implants placed in extraction sockets and three
      trials evaluated different techniques to treat bone dehiscence or fenestrations
      around implants. AUTHORS' CONCLUSIONS: Major bone grafting procedures of
      extremely resorbed mandibles may not be justified. Bone substitutes (Bio-Oss or
      Cerasorb) may replace autogenous bone for sinus lift procedures of extremely
      atrophic sinuses. Both guided bone regeneration (GBR) procedures and distraction
      osteogenesis can augment bone vertically, but it is unclear which is the most
      efficient technique. It is unclear whether augmentation procedures at immediate
      single implants placed in fresh extraction sockets are needed, and which is the
      most effective augmentation procedure, however, sites treated with barrier + Bio
      Oss showed a higher position of the gingival margin, when compared to sites
      treated with barriers alone. Non-resorbable barriers at fenestrated implants
      regenerated more bone than no barriers, however it remains unclear whether such
      bone is of benefit to the patient. It is unclear which is the most effective
      technique for augmenting bone around fenestrated implants. No bone promoting
      molecule has been shown to be effective or necessary in conjunction with dental
      implant treatment. The use of particulated autogenous bone from intraoral
      locations, also taken with dedicated aspirators, might be associated with an
      increased risk of infective complications. These findings are based on few trials
      including few patients, having sometimes short follow up, and being often judged
      to be at high risk of bias.

PMID- 16437461
TI  - Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment
      of venous thromboembolism.
AB  - BACKGROUND: Venous thromboembolism (VTE) is the term given to any thromboembolic
      event (blocking of a blood vessel by a blood clot) occurring in the venous
      system. The current treatment recommended for VTE is anticoagulation (reduction
      of the blood's ability to clot). The aim of this review is to summarize results
      from randomized controlled trials (RCTs) for the effectiveness of anticoagulants
      (heparins, including low molecular weight heparins and vitamin K antagonists) in
      the treatment of VTE, compared to non-steroidal anti-inflammatory drugs (NSAIDs)
      or placebo. OBJECTIVES: To examine the randomized controlled evidence for the
      effectiveness and safety of anticoagulant treatment compared to NSAIDs or placebo
      in patients with VTE on the incidence of fatal and non-fatal pulmonary emboli
      (PE) and the recurrence or extension of deep vein thrombosis (DVT). SEARCH
      STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their
      Specialized Trials Register (last searched 26 July 2005) and the Cochrane Central
      Register of Controlled Trials (CENTRAL) database (last searched Issue 3, 2005).
      In addition, DKC also searched reference lists and contacted pharmaceutical
      companies and experts in the field. SELECTION CRITERIA: All randomized trials of
      anticoagulants versus NSAIDs or placebo in the initial treatment of VTE (DVT or
      PE or both). DATA COLLECTION AND ANALYSIS: DKC and JM independently assessed
      trial quality and extracted data. JCP (biostatistician) analyzed the design
      elements and feasibility of a future randomized controlled trial to determine
      definitively efficacy and safety of anticoagulants in VTE treatment. MAIN
      RESULTS: Two RCTs were included. Data were not pooled because of heterogeneity
      between the studies. The two RCTs were too small to determine any difference in
      mortality, occurrence of pulmonary emboli, progression or return of DVT between
      patients treated with anticoagulation and those receiving no anticoagulation.
      AUTHORS' CONCLUSIONS: The limited evidence from RCTs of anticoagulants versus
      NSAIDs or placebo is inconclusive regarding the efficacy and safety of
      anticoagulants in VTE treatment. The use of anticoagulants is widely accepted in
      clinical practice, so a further RCT comparing anticoagulants to placebo could not
      ethically be carried out.

PMID- 16437462
TI  - Melatonin for cognitive impairment.
AB  - BACKGROUND: There are a number of studies that suggest a relationship between
      decline of melatonin function and the symptoms of dementia. OBJECTIVES: The
      review assessed the evidence of clinical efficacy and safety of melatonin in the
      treatment of manifestations of dementia or cognitive impairment (CI). SEARCH
      STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized
      Register was searched for trials involving melatonin on 5 October 2005. The
      search terms used were MELATONIN, and N-ACETYL-5-METHOXYTRYPTAMINE. This Register
      contains records from all major health care databases as well as many ongoing
      trials databases and is updated regularly. SELECTION CRITERIA: All relevant,
      randomized controlled trials in which orally administered melatonin in any dosage
      was compared with a control group for the effect on managing cognitive,
      behavioural (excluding sleep), and/or affective disturbances of people with
      dementia of any degree of severity. DATA COLLECTION AND ANALYSIS: Two to three
      reviewers independently assessed the retrieved articles for relevance and
      methodological quality, and extracted data from the selected studies.
      Statistically significant differences in changes in outcomes from baseline to end
      of treatment between the melatonin and control groups were examined. Each study
      was summarized using a measure of effect (e.g. mean difference) and meta-analyses
      were conducted when appropriate. MAIN RESULTS: Three studies met the inclusion
      criteria. This review revealed non-significant effects from the pooled estimates
      of MMSE cognitive, and ADAS-cognitive change scores. Individual study estimates
      for treatment effect demonstrated a significant improvement for melatonin
      compared with placebo in behavioural and affective symptoms as measured by the
      ADAS non-cognitive scale in a study of 20 patients, and the Neuropsychiatric
      Inventory (NPI) following treatment with 2.5 mg/day (SR) melatonin, but not with
      10mg/day (IR) melatonin in a larger study of 157 patients. The remainder of the
      treatment effects for affect, behaviour and activities of daily living were non
      significant. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the
      effectiveness of melatonin in managing the cognitive and non-cognitive sequelae
      of dementia.

PMID- 16437463
TI  - Silicon gel sheeting for preventing and treating hypertrophic and keloid scars.
AB  - BACKGROUND: Keloid and hypertrophic scars are common and are caused by a
      proliferation of dermal tissue following skin injury. They cause functional and
      psychological problems for patients, and their management can be difficult. The
      use of silicon gel sheeting to prevent and treat hypertrophic scarring is still
      relatively new, and started in 1981 with treatment of burn scars. OBJECTIVES: To
      determine the effectiveness of silicon gel sheeting for: (1) prevention of
      hypertrophic or keloid scarring in people with newly healed wounds (e.g. post
      surgery); (2) treatment of established scarring in people with existing keloid or
      hypertrophic scars. SEARCH STRATEGY: Trials were identified from searches of the
      Cochrane Wounds Group Specialised Register (searched September 2005), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3,
      2005); MEDLINE (1989 to June 2002); EMBASE (1988 to May 2002); CINAHL (1982 to
      May 2002) and reference lists of articles and relevant reviews. The major
      supplier of silicon gel sheeting (Smith and Nephew) was approached for details of
      unpublished, ongoing and recently published trials. SELECTION CRITERIA: Any
      randomised or quasi-randomised controlled trials, or controlled clinical trials
      comparing silicon gel sheeting for prevention or treatment of hypertrophic or
      keloid scars against no treatment, placebo, or any other treatment type except
      surgery. DATA COLLECTION AND ANALYSIS: All relevant trials were assessed for
      methodological quality. Data were extracted independently by both reviewers using
      a standardized form, and the results cross-checked. All trials, meeting the
      selection criteria were assessed for methodological quality. MAIN RESULTS:
      Thirteen trials, involving 559 people, ranging in age from 2 to 81 years, were
      included in the review. The trials compared adhesive silicon gel sheeting with
      control; non-silicon gel sheeting; silicon gel plates with added Vitamin E; laser
      therapy; triamcinolone acetonide injection, and non-adhesive silicon gel
      sheeting. In the prevention studies, when compared with a no treatment option;
      whilst silicon gel sheeting reduced the incidence of hypertrophic scarring in
      people prone to scarring, (RR 0.46, 95% CI 0.21 to 0.98) these studies were
      highly susceptible to bias. Silicon gel sheeting produced a statistically
      significant improvement in scar elasticity, (RR 8.60, 95% CI 2.55 to 29.02), but
      again these studies were highly susceptible to bias. AUTHORS' CONCLUSIONS: Trials
      evaluating silicon gel sheeting as a treatment for hypertrophic and keloid
      scarring are of poor quality and highly susceptible to bias. There is weak
      evidence of a benefit of silicon gel sheeting as a prevention for abnormal
      scarring in high risk individuals but the poor quality of research means a great
      deal of uncertainty prevails.

PMID- 16437464
TI  - Diuretics for heart failure.
AB  - BACKGROUND: Chronic heart failure is a major cause of morbidity and mortality
      world-wide. Diuretics are regarded as the first-line treatment for patients with
      congestive heart failure since they provide symptomatic relief. The effects of
      diuretics on disease progression and survival remain unclear. OBJECTIVES: To
      assess the harms and benefits of diuretics for chronic heart failure SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Issue 2
      2004), MEDLINE 1966-2004, EMBASE 1980-2004 and HERDIN database. We hand searched
      pertinent journals and reference lists of papers were inspected. We also
      contacted manufacturers and researchers in the field. SELECTION CRITERIA: Only
      double-blinded randomised controlled trials of diuretic therapy comparing one
      diuretic with placebo, or one diuretic with another active agent (e.g. ACE
      inhibitors, digoxin) in patients with chronic heart failure were eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted
      the data and assessed the eligibility and methodological quality of each trial.
      Extracted data were entered into the Review Manager 4.2 computer software, and
      analysed by determining the odds ratio for dichotomous data, and difference in
      means for continuous data, of the treated group compared with controls. The
      likelihood of heterogeneity of the study population was assessed by the Chi
      square test. If there was no evidence of statistical heterogeneity and pooling of
      results was clinically appropriate, a combined estimate was obtained using the
      fixed-effects model. MAIN RESULTS: We included 14 trials (525 participants), 7
      were placebo-controlled, and 7 compared diuretics against other agents such as
      ACE inhibitors or digoxin. We analysed the data for mortality and for worsening
      heart failure. Mortality data were available in 3 of the placebo-controlled
      trials (202 participants). Mortality was lower for participants treated with
      diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence
      interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was
      reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95%
      CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control
      (91 participants), diuretics improved exercise capacity in participants with CHF,
      difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001. AUTHORS'
      CONCLUSIONS: The available data from several small trials show that in patients
      with chronic heart failure, conventional diuretics appear to reduce the risk of
      death and worsening heart failure compared to placebo. Compared to active
      control, diuretics appear to improve exercise capacity.

PMID- 16437465
TI  - Single, double or multiple injection techniques for axillary brachial plexus
      block for hand, wrist or forearm surgery.
AB  - BACKGROUND: Regional anaesthesia comprising axillary block of the brachial plexus
      is a common anaesthetic technique for distal upper extremity surgery. OBJECTIVES:
      To compare the relative effects of anaesthetic techniques using either single,
      double or multiple injections for axillary block of the brachial plexus for
      distal upper extremity surgery. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, as well as reference
      lists of trials. We contacted trial authors and the medical industry. Date of
      last search: August 2004. SELECTION CRITERIA: We included randomized controlled
      trials that compared double with single injection techniques, multiple with
      single injection techniques, or multiple with double injection techniques for
      axillary block in adults undergoing surgery of the distal upper extremity. DATA
      COLLECTION AND ANALYSIS: We performed independent study selection, quality
      assessment and data extraction. We undertook meta-analysis, including exploratory
      analyses according to the method of nerve location and definition of primary
      anaesthesia failure. MAIN RESULTS: The 12 included trials involved a total of 981
      participants who received regional anaesthesia for hand, wrist, forearm or elbow
      surgery. Trial design and conduct was generally adequate although several trials
      failed to monitor longer-term effects and to provide sufficient description of
      their study populations. Substantial heterogeneity precluded the pooling of data
      for primary anaesthesia failure from the five trials comparing double versus
      single injections. However, double injections were significantly more effective
      than single injections in the three trials where electrolocation was used
      throughout (relative risk (RR) 0.31, 95% confidence interval (CI) 0.31 to 0.74).
      Five trials compared multiple with single injections. These showed a
      statistically significant decrease in primary anaesthesia failure (RR 0.24, 95%
      CI 0.13 to 0.46) and incomplete motor block (RR 0.61, 95% CI 0.39 to 0.96) in the
      multiple injection group. Six trials compared multiple with double injections.
      These showed a statistically significant decrease in primary anaesthesia failure
      (RR 0.23, 95% CI 0.14 to 0.38) and incomplete motor block (RR 0.55, 95% CI 0.36
      to 0.85) in the multiple injection group.Generally, none of the differences
      between the two groups of any of the three comparisons in secondary analgesia
      failure, complications and patient discomfort were statistically significant. The
      time for block performance was significantly shorter for single and double
      injections compared with multiple injections, but the requirement for
      supplementary blocks in these groups tended to increase the time to readiness for
      surgery. AUTHORS' CONCLUSIONS: This review provided some evidence that multiple
      injection techniques using nerve stimulation for axillary plexus block provide
      more effective anaesthesia than either double or single injection techniques.
      However, there was insufficient evidence for other outcomes, including safety.

PMID- 16437466
TI  - Sedation of anxious children undergoing dental treatment.
AB  - BACKGROUND: Anxiety about dental treatment or behaviour management problems can
      be a barrier to its uptake in children. Sedation can be used to relieve anxiety
      and manage behaviour, unfortunately it is difficult to determine from published
      research which agents, dosages and techniques are effective. OBJECTIVES: To
      evaluate the relative efficacy of the various conscious sedation techniques and
      dosages for behaviour management in paediatric dentistry. SEARCH STRATEGY:
      Computerised: MEDLINE, PubMed, EMBASE, Cochrane Central Register of Controlled
      Trials, Dissertation Abstracts, SIGLE, the World Wide Web (Google) and the
      Community of Science Database were searched for relevant trials and references up
      to December 2004. Reference lists from relevant articles were scanned and the
      authors contacted to identify trials and obtain additional information. There
      were no language restrictions. Trials pre-1966 were not searched. SELECTION
      CRITERIA: Studies were selected if they met the following criteria: randomised
      controlled trials of conscious sedation comparing two or more
      drugs/techniques/placebo undertaken by the dentist or one of the dental team in
      anxious children up to 16 years of age. DATA COLLECTION AND ANALYSIS: Information
      regarding methods, participants, interventions and outcome measures and results
      were independently extracted, in duplicate, by two authors. Authors of trials
      were contacted for details of randomisation and withdrawals and a quality
      assessment was carried out not using any formal scoring system. The Cochrane Oral
      Health Group statistical guidelines were followed. MAIN RESULTS: Sixty-one
      studies were included with 3246 subjects in total. Overall quality of studies was
      found to be disappointing with poor reporting often the main problem. Data
      reported could not be easily aggregated into groups to facilitate description of
      results. Meta-analysis of the available data was also not possible for the same
      reason. The variety of differing drug regimens compared made it difficult to
      isolate groups of studies that were sufficiently similar in design to allow
      sensible comparison. Where groups of studies could be isolated, then the
      differing outcome measures used made their meta-analysis impossible. AUTHORS'
      CONCLUSIONS: Review authors were not able to reach any definitive conclusion on
      which was the most effective drug or method of sedation used for anxious
      children. A list of proposed areas of study was described.

PMID- 16437467
TI  - Oral betamimetics for maintenance therapy after threatened preterm labour.
AB  - BACKGROUND: Some women who have threatened to give birth prematurely,
      subsequently settle. They may then take oral tocolytic maintenance therapy to
      prevent preterm birth and to prolong gestation. OBJECTIVES: To assess the effects
      of oral betamimetic maintenance therapy after threatened preterm labour for
      preventing preterm birth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Trials Register (June 2005) and MEDLINE (from 1966 to August 2003).
      SELECTION CRITERIA: Randomised controlled trials comparing oral betamimetic with
      alternative tocolytic therapy, placebo or no therapy, for maintenance following
      treatment of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two review
      authors independently applied the selection criteria and carried out data
      extraction and quality assessment of studies. MAIN RESULTS: Eleven randomised
      controlled trials (RCTs) were included. No differences were seen for admission to
      the neonatal intensive care unit when betamimetics were compared with placebo
      (relative risk (RR) 1.29, 95% confidence interval (CI) 0.64 to 2.60; one RCT of
      terbutaline with 140 women) or with magnesium (RR 0.80, 95% CI 0.43 to 1.46; one
      RCT of 137 women). The rate of preterm birth (less than 37 weeks) showed no
      significant difference in four RCTs, two comparing ritodrine with placebo/no
      treatment and two comparing terbutaline with placebo/no treatment (RR 1.08, 95%
      CI 0.88 to 1.32, 384 women). No differences between betamimetics and placebo, no
      treatment or other tocolytics were seen for perinatal mortality and morbidity
      outcomes. Some adverse effects such as tachycardia were more frequent in the
      betamimetics groups than the groups allocated to placebo, no treatment or another
      type of tocolytic. AUTHORS' CONCLUSIONS: Available evidence does not support the
      use of oral betamimetics for maintenance therapy after threatened preterm labour.

PMID- 16437468
TI  - Higher versus lower protein intake in formula-fed low birth weight infants.
AB  - BACKGROUND: The ideal quantity of dietary protein for formula-fed low birth
      weight infants < 2.5 kilograms is still a matter of controversy and debate. In
      premature infants, the protein intake must be sufficient to achieve normal growth
      without negative effects such as acidosis, uremia, and elevated levels of
      circulating amino acids (e.g. phenylalanine levels). This systematic review
      evaluates the benefits and risks of higher (>= 3.0 g/kg/day) versus lower (< 3.0
      g/kg/day) protein intakes during the initial hospital stay of formula-fed preterm
      infants < 2.5 kilograms. OBJECTIVES: To determine whether higher (>= 3.0
      g/kg/day) versus lower (< 3.0 g/kg/day) protein intakes during the initial
      hospital stay of formula-fed preterm infants < 2.5 kilograms result in improved
      growth and neurodevelopmental outcomes without evidence of short and long-term
      morbidity. SEARCH STRATEGY: Two review authors searched MEDLINE (1966 - May
      2005), CINAHL (1982 - May 2005), PubMed (1966 - May 2005), EMBASE (1980 - May
      2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
      Library, Issue 2, 2005), abstracts, conferences and symposia proceedings from
      Society of Pediatric Research, and American Academy of Pediatrics. Cross
      references were reviewed independently for additional relevant titles and
      abstracts for articles up to fifty years old. SELECTION CRITERIA: Randomized
      controlled trials contrasting levels of formula protein intakes as low (< 3.0
      g/kg/day), high (=> 3.0 g/kg/day but < 4.0 g/kg/day), or very high protein intake
      (=> 4.0 g/kg/day) during hospitalization of neonates less than 2.5 kilograms at
      birth who were formula-fed. Studies were not included if infants received partial
      parenteral nutrition during the study period or were fed formula as a supplement
      to human milk. Given the small number of studies that met all inclusion criteria,
      studies in which nutrients other than protein also varied (> 10% relative
      difference) were added in a post-facto analysis. DATA COLLECTION AND ANALYSIS:
      Two review authors used standard methods of the Cochrane Collaboration and of the
      Cochrane Neonatal Review Group to independently assess trial eligibility and
      quality, and extracted data. In a 3-arm trial where two groups fell within the
      same predesignated protein intake group, weighted means and pooled standard
      deviations were calculated. MAIN RESULTS: The literature search identified 37
      studies, of which five met all the inclusion criteria. All five studies compared
      low (< 3.0 g/kg/day) to high protein intakes (=> 3.0 g/kg/day but < 4.0
      g/kg/day). The overall analysis revealed an improved weight gain (WMD 2.36
      g/kg/day, 95% CI 1.31, 3.40) and higher nitrogen accretion (WMD 143.7 mg/kg/day,
      95% CI 128.7, 158.8) in infants receiving formula with higher protein content
      while other nutrients were kept constant. None of the studies reported IQ or
      Bayley scores at 18 months or later. No significant differences were seen in
      rates of necrotizing enterocolitis, sepsis or diarrhea. Of three studies included
      in the post-facto analysis, only one could be included in the meta-analysis. The
      post-facto analysis revealed further improvement in all growth parameters in
      infants receiving formula with higher protein content (weight gain: WMD 2.53
      g/kg/day, 95% CI 1.62, 3.45, linear growth: WMD 0.16 cm/week, 95% CI 0.03, 0.30,
      and head growth: WMD 0.23, 95% CI 0.12, 0.35). There was no significant
      difference (WMD 0.25, 95% CI -0.20, 0.70) in the concentration of plasma
      phenylalanine between the high and low protein intake groups. One study (Goldman
      1969) in the post-facto analysis documented a significantly increased incidence
      of low IQ scores, below 90, in infants of birth weight less than 1300 grams who
      received a very high protein intake (6 to 7.2 g/kg/day). AUTHORS' CONCLUSIONS:
      This systematic review suggests that higher protein intake (=> 3.0 g/kg/day but <
      4.0 g/kg/day) from formula accelerates weight gain. Based on increased nitrogen
      accretion rates, this most likely indicates an increase in lean body mass.
      Although accelerated weight gain is considered to be a positive effect, increase
      in other outcome measures examined may represent a negative or ambivalent effect.
      These include elevated blood urea nitrogen levels and increased metabolic
      acidosis. Limited information was available regarding the impact of higher
      formula protein intakes on long term outcomes such as neurodevelopmental
      abnormalities. As determined in this review, existing research literature on this
      topic is not adequate to make specific recommendations regarding the provision of
      very high protein intake (> 4.0 g/kg/day) from formula.

PMID- 16437469
TI  - Decompressive craniectomy for the treatment of refractory high intracranial
      pressure in traumatic brain injury.
AB  - BACKGROUND: High intracranial pressure (ICP) is the most frequent cause of death
      and disability after severe traumatic brain injury (TBI). High ICP is treated by
      general maneuvers (normothermia, sedation etc) and a set of first line
      therapeutic measures (moderate hypocapnia, mannitol etc). When these measures
      fail to control high ICP, second line therapies are started. Among these, second
      line therapies such as barbiturates, hyperventilation, moderate hypothermia or
      removal of a variable amount of skull bone (known as decompressive craniectomy)
      are used. OBJECTIVES: To assess the effects of secondary decompressive
      craniectomy (DC) on outcome and quality of life in patients with severe TBI in
      whom conventional medical therapeutic measures have failed to control raised ICP.
      SEARCH STRATEGY: We searched the Cochrane Injuries Group's Trial Register,
      CENTRAL, MEDLINE, EMBASE, Best Evidence, Clinical Practice Guidelines, PubMed,
      CINAHL, the National Research Register and Google Scholar. We also handsearched
      relevant conference proceedings and contacted experts in the field and the
      authors of included studies. SELECTION CRITERIA: Randomized or quasi-randomized
      studies assessing patients over the age of 12 months with a severe TBI who
      underwent DC to control ICP refractory to conventional medical treatments. DATA
      COLLECTION AND ANALYSIS: Two authors independently examined the electronic search
      results for reports of possibly relevant trials and for retrieval in full. One
      author applied the selection criteria, performed the data extraction and assessed
      methodological quality. Study authors were contacted for additional information.
      MAIN RESULTS: We found one trial with 27 participants conducted in the pediatric
      population (>18 years). DC was associated with a risk ratio (RR) for death of
      0.54 (95% CI 0.17 to 1.72), and RR of 0.54 for death, vegetative status or severe
      disability 6 to 12 months after injury (95% CI 0.29 to 1.07). AUTHORS'
      CONCLUSIONS: There is no evidence to support the routine use of secondary DC to
      reduce unfavourable outcome in adults with severe TBI and refractory high ICP. In
      the pediatric population DC reduces the risk of death and unfavourable outcome.
      Despite the wide confidence intervals for death and the small sample size of the
      only study identified, this treatment maybe justified in patients below the age
      of 18 when maximal medical treatment has failed to control ICP. To date, there
      are no results from randomised trials to confirm or refute the effectiveness of
      DC in adults. However, the results of non-randomized trials and controlled trials
      with historical controls involving adults, suggest that DC may be a useful option
      when maximal medical treatment has failed to control ICP. There are two ongoing
      randomized controlled trials of DC (Rescue ICP and DECRAN) that may allow further
      conclusions on the efficacy of this procedure in adults.

PMID- 16437470
TI  - Combination contraceptives: effects on weight.
AB  - BACKGROUND: Weight gain is often considered a side effect of combination hormonal
      contraceptives, and many women and clinicians believe that an association exists.
      Concern about weight gain can limit the use of this highly effective method of
      contraception by deterring the initiation of its use and causing early
      discontinuation among users. However, a causal relationship between combination
      contraceptives and weight gain has not been established. OBJECTIVES: The aim of
      the review was to evaluate the potential association between combination
      contraceptive use and changes in weight. SEARCH STRATEGY: We searched the
      computerized databases MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies
      of combination contraceptives. We also wrote to known investigators and
      manufacturers to request information about other published or unpublished trials
      not discovered in our search. SELECTION CRITERIA: All English-language,
      randomized controlled trials were eligible if they had at least three treatment
      cycles and compared a combination contraceptive to a placebo or to a combination
      contraceptive that differed in drug, dosage, regimen, and/or study length. DATA
      COLLECTION AND ANALYSIS: All titles and abstracts located in the literature
      searches were assessed. Data were entered and analyzed with RevMan, and a second
      author verified the data entered. Depending on the data available, the weighted
      mean difference using a fixed effects model with 95% confidence intervals (CI)
      was calculated for the mean change in weight between baseline and post-treatment
      measurements or the Peto odds ratio with 95% confidence intervals was calculated
      using the proportion of women who gained or lost more than a specified amount of
      weight. MAIN RESULTS: The three placebo-controlled, randomized trials did not
      find evidence supporting a causal association between combination oral
      contraceptives or a combination skin patch and weight gain. Most comparisons of
      different combination contraceptives showed no substantial difference in weight.
      In addition, discontinuation of combination contraceptives because of weight gain
      did not differ between groups where this was studied. AUTHORS' CONCLUSIONS:
      Available evidence was insufficient to determine the effect of combination
      contraceptives on weight, but no large effect was evident.

PMID- 16437471
TI  - Steroids for idiopathic sudden sensorineural hearing loss.
AB  - BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSHL) is a clinical
      diagnosis characterised by a sudden deafness of cochlear or retrocochlear origin
      in the absence of a clear precipitating cause. Steroids are commonly prescribed
      to treat this condition. There is no consensus on their effectiveness.
      OBJECTIVES: To determine the effectiveness and the side-effect profile of
      steroids in the treatment of idiopathic sudden sensorineural hearing loss. SEARCH
      STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to December 2004)
      and EMBASE (1974 to December 2004). Reference lists of all trials were also
      manually searched. SELECTION CRITERIA: We identified all randomised controlled
      trials (with or without blinding) in which steroids were evaluated in comparison
      with either no treatment or a placebo. Trials including the use of steroids in
      combination with another treatment were considered if the comparison control
      group also received the same other treatment. The full text articles of all the
      retrieved trials of possible relevance were reviewed by the two authors and the
      inclusion criteria applied independently. Any differences in opinion about which
      studies to include in the reviews were resolved by discussion. DATA COLLECTION
      AND ANALYSIS: Trials were graded for methodological quality using the Cochrane
      approach. The data extraction was performed in a standardised manner by one
      author and rechecked by the other author, and where necessary investigators were
      contacted to obtain the missing information. Meta-analysis was neither possible
      nor considered appropriate because of the heterogeneity of the populations
      studied, the differences in steroid formulations, dosages and duration of the
      treatment. The quality of the result of each study was analysed and reported
      individually. A narrative overview of the result is presented. MAIN RESULTS: Only
      two trials satisfied the inclusion criteria and both were of low methodological
      quality. One trial showed a lack of effect of oral steroids in hearing
      improvement compared with the placebo control group. The other trial showed a
      significant improvement of hearing in 61% of the patients receiving oral steroid
      and in only 32% of the patients from the control group (combination of placebo
      treated group and untreated control group). There was no clear evidence presented
      in the former study about any harmful side effects of the steroids. The latter
      study declared that no patients suffered from adverse effects from the steroid
      treatment. AUTHORS' CONCLUSIONS: The value of steroids in the treatment of
      idiopathic sudden sensorineural hearing loss remains unclear since the evidence
      obtained from randomised controlled trials are contradictory in outcome, in part
      because the studies are based upon too small a number of patients.

PMID- 16437472
TI  - Risperidone alone or in combination for acute mania.
AB  - BACKGROUND: Risperidone, an atypical antipsychotic, is used to treat mania both
      alone and in combination with other medicines. OBJECTIVES: To review the efficacy
      and tolerability of risperidone as treatment for mania. SEARCH STRATEGY: The
      Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials
      Register (CCDANCTR-Studies December 2004), The Cochrane Central Register of
      Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched
      in December 2004. Reference lists and English language textbooks were searched;
      researchers in the field and Janssen-Cilag were contacted. SELECTION CRITERIA:
      Randomised controlled trials comparing risperidone with placebo or other drugs in
      acute manic or mixed episodes. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data from trial reports. Janssen-Cilag was asked to
      provide missing information. QUALITY ASSESSMENT: As in other trials of treatment
      for mania, the high proportion of imputed efficacy data resulting from rates of
      failure to complete treatment of between 12% and 62% may have biased the results.
      MAIN RESULTS: Six trials (1343 participants) of risperidone as monotherapy or as
      adjunctive treatment to lithium, or an anticonvulsant, were identified. Permitted
      doses were consistent with those recommended by the manufacturers of Haldol
      (haloperidol) and Risperdal (risperidone) for treatment of mania and trials
      involving haloperidol allowed antiparkinsonian treatment. Risperidone monotherapy
      was more effective than placebo in reducing manic symptoms, using the Young Mania
      Rating Scale (YMRS) (weighted mean difference (WMD) -5.75, 95% confidence
      interval (CI) -7.46 to -4.04, P<0.00001; 2 trials) and in leading to response,
      remission and sustained remission. Effect sizes for monotherapy and adjunctive
      treatment comparisons were similar. Low levels of baseline depression precluded
      reliable assessment of efficacy for treatment of depressive symptoms. Risperidone
      as monotherapy and as adjunctive treatment was more acceptable than placebo, with
      lower incidence of failure to complete treatment (RR 0.66, 95% CI 0.52 to 0.82, P
      = 0.0003; 5 trials). Overall risperidone caused more weight gain, extrapyramidal
      disorder, sedation and increase in prolactin level than placebo. There was no
      evidence of a difference in efficacy between risperidone and haloperidol either
      as monotherapy or as adjunctive treatment. The acceptability of risperidone and
      haloperidol in incidence of failure to complete treatment was comparable. Overall
      risperidone caused more weight gain than haloperidol but less extrapyramidal
      disorder and comparable sedation. AUTHORS' CONCLUSIONS: Risperidone, as
      monotherapy and adjunctive treatment, is effective in reducing manic symptoms.
      The main adverse effects are weight gain, extrapyramidal effects and sedation.
      Risperidone is comparable in efficacy to haloperidol. Higher quality trials are
      required to provide more reliable and precise estimates of its costs and
      benefits.

PMID- 16437473
TI  - Herbal medicines for treatment of irritable bowel syndrome.
AB  - BACKGROUND: Traditional herbal therapies have been used for a long time to treat
      gastrointestinal disorders including irritable bowel syndrome, and their
      effectiveness from clinical research evidence needs to be systematically
      reviewed. OBJECTIVES: To assess the effectiveness and safety of herbal medicines
      in patients with irritable bowel syndrome. SEARCH STRATEGY: We searched the
      following electronic databases till July 2004: The Cochrane Library (CENTRAL),
      MEDLINE, EMBASE, AMED, LILACS, the Chinese Biomedical Database, combined with
      hand searches of Chinese journals and conference proceedings till end of 2003. No
      language restriction was used. SELECTION CRITERIA: Randomised controlled trials
      of herbal medicines compared with no treatment, placebo, pharmacological
      interventions were included. DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by two authors. The methodological quality of trials was evaluated
      using the components of randomisation, allocation concealment, double blinding,
      and inclusion of randomised participants. MAIN RESULTS: Seventy-five randomised
      trials, involving 7957 participants with irritable bowel syndrome, met the
      inclusion criteria. The methodological quality of three double-blind, placebo
      controlled trials was high, but the quality of remaining trials was generally
      low. Seventy-one different herbal medicines were tested in the included trials,
      in which herbal medicines were compared with placebo or conventional
      pharmacologic therapy. Herbal medicines were also combined with conventional
      therapy and compared to conventional therapy alone.Compared with placebo, a
      Standard Chinese herbal formula, individualised Chinese herbal medicine, STW 5
      and STW 5-II, Tibetan herbal medicine Padma Lax, traditional Chinese formula
      Tongxie Yaofang, and Ayurvedic preparation showed significantly improvement of
      global symptoms. Compared with conventional therapy in 65 trials testing 51
      different herbal medicines, 22 herbal medicines demonstrated a statistically
      significant benefit for symptom improvement, and 29 herbal medicines were not
      significantly different than conventional therapy. In nine trials that evaluated
      herbal medicine combined with conventional therapy, six tested herbal
      preparations showed additional benefit from the combination therapy compared with
      conventional monotherapy. No serious adverse events from the herbal medicines
      were reported. AUTHORS' CONCLUSIONS: Some herbal medicines may improve the
      symptoms of irritable bowel syndrome. However, positive findings from less
      rigorous trials should be interpreted with caution due to inadequate methodology,
      small sample sizes, and lack of confirming data. Some herbal medicines deserve
      further examination in high-quality trials.

PMID- 16437474
TI  - Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease.
AB  - BACKGROUND: Spasticity commonly affects patients with motor neuron disease. It is
      likely to contribute to worsening muscle dysfunction, increased difficulty with
      activities of daily living and deteriorating quality of life. OBJECTIVES: The
      objective of this review is to systematically review treatments for spasticity in
      amyotrophic lateral sclerosis, also known as motor neuron disease. SEARCH
      STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register
      (January 2003 and January 2005), MEDLINE (January 1966 to February 2005), EMBASE
      (January 1980 to February 2005), CINAHL (January 1982 to February 2005), AMED
      (January 1985 to February 2005) and LILACS (January 1982 to January 2003). We
      reviewed the bibliographies of the randomized controlled trials identified, and
      contacted authors and experts in the field. SELECTION CRITERIA: We included quasi
      randomized or randomized controlled trials of participants with probable or
      definite amyotrophic lateral sclerosis according to the El Escorial diagnostic
      criteria (or a revised version) or the Airlie House revision. We would have
      included trials of physical therapy, modalities, prescription medications, non
      prescription medications, chemical neurolysis, surgical interventions, and
      alternative therapies. Our primary outcome measure was reduction in spasticity at
      three months or greater as measured by the Ashworth (or modified Ashworth)
      spasticity scale. Our secondary outcome measures were: validated measures based
      on history, physical examination, physiological measures, measures of function,
      measures of quality of life, serious adverse events, and measures of cost. DATA
      COLLECTION AND ANALYSIS: We identified only one randomized controlled trial that
      met our inclusion criteria. Two authors extracted the data. We also contacted the
      author of the paper and obtained information not available in the published
      article. MAIN RESULTS: The included study was a trial of moderate intensity,
      endurance type exercise versus 'usual activities' in 25 patients with amyotrophic
      lateral sclerosis. At three months patients performing the 15 minute twice daily
      exercises had significantly less spasticity overall (mean reduction of -0.43, 95%
      CI -1.03 to +0.17 in the treatment group versus an increase of +0.25, 95% CI 
      0.46 to +0.96 in control) but the mean change between groups was not significant
      (-0.68, 95% CI -1.62 to +0.26), as measured by the Ashworth scale. AUTHORS'
      CONCLUSIONS: The single trial performed was too small to determine whether
      individualised moderate intensity endurance type exercises for the trunk and
      limbs are beneficial or harmful. No other medical, surgical or alternative
      treatment and therapy has been evaluated in a randomized fashion in this patient
      population. More research is needed.

PMID- 16437475
TI  - D-penicillamine for primary sclerosing cholangitis.
AB  - BACKGROUND: Primary sclerosing cholangitis is a cholestatic disease. D
      penicillamine is suggested as a treatment option due to its copper reducing and
      immunomodulatory potential. OBJECTIVES: To evaluate the beneficial and harmful
      effects of D-penicillamine for patients with primary sclerosing cholangitis.
      SEARCH STRATEGY: Eligible trials were identified through searches of The Cochrane
      Hepato-Biliary Group Controlled Trials Register (August 2005), The Cochrane
      Central Register of Controlled Trials in The Cochrane Library (Issue 3, 2005),
      MEDLINE (1950 to August 2005), EMBASE (1980 to August 2005), Science Citation
      Index EXPANDED (1945 to August 2005), and reference lists of relevant articles.
      Authors of trials and pharmaceutical companies known to produce D-penicillamine
      were also contacted. SELECTION CRITERIA: Randomised clinical trials comparing D
      penicillamine in any dose, duration, and route of administration versus placebo,
      no intervention, or other intervention(s). Trials were included irrespective of
      publication status, year of publication, language, or blinding. DATA COLLECTION
      AND ANALYSIS: Both authors selected the trials, extracted data, and evaluated the
      methodological quality of the trials with respect to the generation of allocation
      sequence, allocation concealment, blinding, and follow-up. The results were
      reported by intention-to-treat analysis. The outcomes were presented as relative
      risk (RR) or weighted mean difference (WMD), both with 95% confidence intervals
      (CI). MAIN RESULTS: One randomised trial was identified and included in the
      review. It was of low methodological quality. The trial compared D-penicillamine
      versus placebo in 70 patients with primary sclerosing cholangitis. Compared with
      placebo, D-penicillamine therapy had no significant effect on mortality (RR 1.14,
      95% CI 0.49 to 2.64), liver transplantation (RR 1.11, 95% CI 0.39 to 3.17),
      hepatic histologic progression (RR 1.17, 95% CI 0.79 to 1.74), or
      cholangiographic deterioration (RR 0.87, 95% CI 0.43 to 1.79). D-penicillamine
      led to a significant improvement in the serum aspartate aminotransferase (WMD 
      23.00 U/L; 95% CI -30.66 to -15.34), but not in serum bilirubin level (WMD 0.40
      mg/L; 95% CI -0.19 to 0.99) and serum alkaline phosphatases activity (WMD 44.00
      U/L; 95% CI -37.89 to 125.89). There were significantly more adverse events in
      patients receiving D-penicillamine (P = 0.013). AUTHORS' CONCLUSIONS: There is
      not sufficient evidence to support or refute the use of D-penicillamine for
      patients with primary sclerosing cholangitis. We do not recommend the use of D
      penicillamine for patients with primary sclerosing cholangitis outside randomised
      trials.

PMID- 16437476
TI  - Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with
      cystic fibrosis.
AB  - BACKGROUND: Lower respiratory tract infection with Pseudomonas aeruginosa (P.
      aeruginosa) occurs in most people with cystic fibrosis. Once chronic infection is
      established, P. aeruginosa is virtually impossible to eradicate and is associated
      with increased mortality and morbidity. Early infection may be easier to
      eradicate. OBJECTIVES: To determine whether antibiotic treatment of early P.
      aeruginosa infection in children and adults with cystic fibrosis eradicates the
      organism and improves clinical and microbiological outcome. SEARCH STRATEGY: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register
      which comprises of references identified from comprehensive electronic database
      searches and handsearches of relevant journals and abstract books of conference
      proceedings. Date of most recent search: May 2004 SELECTION CRITERIA: We included
      randomised controlled trials of people with cystic fibrosis, in whom P.
      aeruginosa had recently been isolated from respiratory secretions. We compared
      combinations of inhaled, oral or intravenous antibiotics with placebo or usual
      treatment (or both) or other combinations of inhaled, oral or intravenous
      antibiotics. We excluded non-randomised trials, cross-over trials, and those
      utilising historical controls. DATA COLLECTION AND ANALYSIS: Both authors
      independently assessed selected trials, assessed methodological quality and
      extracted data. MAIN RESULTS: The search identified 15 trials. Three trials (69
      participants) were eligible for inclusion. There is evidence from two randomised
      controlled trials, of questionable methodological quality, that treatment of
      early P. aeruginosa infection with inhaled tobramycin results in microbiological
      eradication of the organism from respiratory secretions more often than placebo
      and that this effect may persist for up to 12 months, however incomplete data
      from one of the trials precludes an accurate analysis. One randomised controlled
      trial of oral ciprofloxacin and nebulised colisitin versus usual treatment was
      identified. This trial was of poor methodological quality. The results suggested
      treatment of early infection results in microbiological eradication of P.
      aeruginosa more often than usual treatment, after two years, RR 0.24 (95% CI 0.06
      to 0.96). There is insufficient evidence to determine whether antibiotic
      strategies for the eradication of early P. aeruginosa decrease mortality or
      morbidity, improve quality of life, or are associated with adverse effects
      compared to placebo or standard treatment. AUTHORS' CONCLUSIONS: From the three
      trials included in this review, there is some evidence that antibiotic treatment
      of early P. aeruginosa results in short-term eradication but it remains uncertain
      whether there is clinical benefit to people with cystic fibrosis.

PMID- 16437477
TI  - Palliative biliary stents for obstructing pancreatic carcinoma.
AB  - BACKGROUND: Palliative endoscopic stents or surgical by-pass are often required
      for inoperable pancreatic carcinoma to relieve symptomatic obstruction of the
      distal biliary tree. The optimal method of intervention remains unknown.
      OBJECTIVES: To compare surgery, metal endoscopic stents and plastic endoscopic
      stents in the relief of distal biliary obstruction in patients with inoperable
      pancreatic carcinoma. SEARCH STRATEGY: We searched the databases of the Cochrane
      Upper Gastrointestinal and Pancreatic Group specialised register, Cochrane
      Central Register of Controlled Trials , MEDLINE, EMBASE, CancerLit, Current
      Concepts Database and BIDS (September 2002 to September 2004). Reference lists of
      articles and published abstracts from UEGW and DDW were hand-searched. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing surgery to endoscopic
      stenting, endoscopic metal stents to plastic stents, and different types of
      endoscopic plastic and metal stents, used to relieve obstruction of the distal
      bile duct in patients with inoperable pancreatic carcinoma. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial quality and extracted data.
      Adverse effects information was collected from the trials. MAIN RESULTS: Twenty
      one trials involving 1,454 people were included. Based on meta-analysis,
      endoscopic stenting with plastic stents appears to be associated with a reduced
      risk of complications (RR 0.60, 95% CI 0.45 - 0.81), but with higher risk of
      recurrent biliary obstruction prior to death (RR 18.59, 95% CI 5.33 - 64.86) when
      compared with surgery. There was a trend towards higher 30-day mortality in the
      surgical group (p=0.07, RR 0.58, 95% CI 0.32, 1.04). There was no evidence of a
      difference in technical or therapeutic success. Other outcomes were not suitable
      for meta-analysis. No trials comparing endoscopic metal stents to surgery were
      identified. In endoscopic stent comparisons, metal biliary stents appear to have
      a lower risk of recurrent biliary obstruction than plastic stents (RR 0.52, 95%
      CI 0.39 - 0.69). There was no significant statistical difference in technical
      success, therapeutic success, complications or 30-day mortality using meta
      analysis. A narrative review of studies of the cost-effectiveness of metal stents
      drew conflicting conclusions, but results may be dependent on the patients'
      length of survival. Neither Teflon, hydrourethane, or hydrophilic coating appear
      to improve the patency of plastic stents above polyethylene in the trials
      reviewed. Only perflouro alkoxy plastic stents had superior outcome to
      polyethylene stents in one trial. The single eligible trial comparing types of
      metal stents reported higher patency with covered stents, but also a higher risk
      of complications. These results are based on review of the trials individual
      results only. AUTHORS' CONCLUSIONS: Endoscopic metal stents are the intervention
      of choice at present in patients with malignant distal obstructive jaundice due
      to pancreatic carcinoma. In patients with short predicted survival, their patency
      benefits over plastic stents may not be realised. Further RCTs are needed to
      determine the optimal stent type for these patients.

PMID- 16437478
TI  - Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low
      birth weight infants.
AB  - BACKGROUND: A patent ductus arteriosus (PDA) often complicates the clinical
      course of preterm infants and increases the risk of intraventricular hemorrhage
      (IVH), necrotizing enterocolitis (NEC), chronic lung disease (CLD) and death. The
      standard treatment to close a PDA is indomethacin. Its use is associated with
      renal, gastrointestinal and cerebral side-effects. Ibuprofen has been shown to be
      effective in closing a PDA without reducing blood flow velocity to the brain, gut
      or kidneys. OBJECTIVES: To determine the effectiveness and safety of prophylactic
      ibuprofen compared to placebo/no intervention or other cyclo-oxygenase inhibitor
      drugs (indomethacin, mefenamic acid, etc) in the prevention of PDA in preterm
      infants. SEARCH STRATEGY: Randomized controlled trials comparing prophylactic
      ibuprofen use with placebo/no intervention/indomethacin were identified by
      searching the Cochrane Central Register of Controlled Trial (CENTRAL, The
      Cochrane Library, Issue 3, 2005), MEDLINE (1966-July 2005), CINAHL (1982-July
      2005), EMBASE (1980-July 2005), reference lists of published trials and abstracts
      published in Pediatric Research (1990-July 2005). No language restrictions were
      applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials
      comparing use of ibuprofen with placebo/no intervention or other cyclo-oxygenase
      inhibitor drugs (indomethacin, mefenamic acid, etc) for the prevention of PDA in
      preterm and/or low birth weight infants. DATA COLLECTION AND ANALYSIS: Data
      regarding the clinical outcomes including presence of PDA on day three and day
      seven, need for surgical ligation, need for rescue treatment with cyclo-oxygenase
      inhibitors, IVH, mortality, renal and gastrointestinal complications were
      extracted. Meta-analyses were performed using RevMan 4.2 and treatment estimates
      were reported as weighted mean difference (WMD), typical relative risk (RR),
      typical risk difference (RD) and, if statistically significant, number needed to
      treat (NNT) or number needed to harm (NNH), along with their 95% confidence
      intervals (CI). MAIN RESULTS: Four trials (n = 672) were included in the review.
      There was a statistically significant decrease in the incidence of PDA on day
      three in the ibuprofen group [typical RR 0.37 (95% CI 0.29, 0.49); typical RD 
      0.29 (95% CI -0.35, -0.22); NNT 3 (95% CI 3, 5); 4 trials, n = 672], in the need
      for rescue treatment with cyclo-oxygenase inhibitors [typical RR 0.17 (95% CI
      0.11, 0.27), typical RD -0.27 (95% CI -0.35, -0.22); NNT 4 (95%CI 3, 5), and in
      the need for surgical ligation [typical RR 0.34 (95% CI 0.14, 0.81), typical RD 
      0.04 (95% CI -0.07, -0.01); NNT 25 (95% CI 14, 100). The PDA had closed
      spontaneously by day three in 60% of the neonates in the control group. There was
      a significant increase in the serum creatinine levels in the ibuprofen group [WMD
      0.13 mg/dl (95% CI 0.08, 0.17); 2 trials, n = 495]. Ibuprofen reduces urine
      output. There were no statistically significant differences in mortality, grade
      3/4 intraventricular hemorrhage, chronic lung disease at 28 days or 36 weeks,
      necrotizing enterocolitis , gastrointestinal hemorrhage, intestinal perforation
      or time to reach full feeds. One trial (Gournay 2002) (n = 135) reported on three
      infants in the ibuprofen group who developed pulmonary hypertension responsive to
      nitric oxide treatment. AUTHORS' CONCLUSIONS: Prophylactic use of ibuprofen
      reduces the incidence of PDA, the need for rescue treatment with cyclo-oxygenase
      inhibitors and surgical closure. However, in the control group, the PDA had
      closed spontaneously by day three in 60% of the neonates. Prophylactic treatment
      therefore exposes a large proportion of infants unnecessarily to a drug that has
      important side effects (mainly involving the kidneys) without conferring any
      important short term benefits. Prophylactic treatment with ibuprofen is not
      recommended. Until long-term follow-up results are published from the trials
      included in this review, no further trials of prophylactic ibuprofen are
      recommended.

PMID- 16437479
TI  - Acetaminophen for osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. Published
      guidelines and expert opinion are divided over the relative role of acetaminophen
      (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs
      (NSAIDs) as first-line pharmacologic therapy. The comparative safety of
      acetaminophen and NSAIDs is also important to consider. This update to the
      original 2003 review includes nine additional RCTs. OBJECTIVES: To assess the
      efficacy and safety of acetaminophen versus placebo and versus NSAIDs (ibuprofen,
      diclofenac, arthrotec, celecoxib, naproxen, rofecoxib) for treating OA. SEARCH
      STRATEGY: We searched MEDLINE (up to July 2005), EMBASE (2002-July 2005),
      Cochrane Central Register of Controlled Trials (CENTRAL), ACP Journal Club, DARE,
      Cochrane Database of Systematic Reviews (all from 1994 to July 2005). Reference
      lists of identified RCTs and pertinent review articles were also hand searched.
      SELECTION CRITERIA: Published randomized controlled trials (RCTs) evaluating the
      efficacy and safety of acetaminophen alone in OA were considered for inclusion.
      DATA COLLECTION AND ANALYSIS: Pain, physical function and global assessment
      outcomes were reported. Results for continuous outcome measures were expressed as
      standardized mean differences (SMD). Dichotomous outcome measures were pooled
      using relative risk (RR) and the number needed to treat (NNT) was calculated.
      MAIN RESULTS: Fifteen RCTs involving 5986 participants were included in this
      review. Seven RCTs compared acetaminophen to placebo and ten RCTs compared
      acetaminophen to NSAIDs. In the placebo-controlled RCTs, acetaminophen was
      superior to placebo in five of the seven RCTs and had a similar safety profile.
      Compared to placebo, a pooled analysis of five trials of overall pain using
      multiple methods demonstrated a statistically significant reduction in pain (SMD 
      0.13, 95% CI -0.22 to -0.04), which is of questionable clinical significance. The
      relative percent improvement from baseline was 5% with an absolute change of 4
      points on a 0 to 100 scale. The NNT to achieve an improvement in pain ranged from
      4 to 16. In the comparator-controlled RCTs, acetaminophen was less effective
      overall than NSAIDs in terms of pain reduction, global assessments and in terms
      of improvements in functional status. No significant difference was found overall
      between the safety of acetaminophen and NSAIDs, although patients taking
      traditional NSAIDS were more likely to experience an adverse GI event (RR 1.47,
      (95% CI 1.08 to 2.00). 19% of patients in the traditional NSAID group versus 13%
      in the acetaminophen group experienced an adverse GI event. However, the median
      trial duration was only 6 weeks and it is difficult to assess adverse outcomes in
      a relatively short time period. AUTHORS' CONCLUSIONS: The evidence to date
      suggests that NSAIDs are superior to acetaminophen for improving knee and hip
      pain in people with OA. The size of the treatment effect was modest, and the
      median trial duration was only six weeks, therefore, additional considerations
      need to be factored in when making the decision between using acetaminophen or
      NSAIDs. In OA subjects with moderate-to-severe levels of pain, NSAIDs appear to
      be more effective than acetaminophen.

PMID- 16437480
TI  - Surgery versus primary endocrine therapy for operable primary breast cancer in
      elderly women (70 years plus).
AB  - BACKGROUND: Several studies have evaluated the clinical effectiveness of
      endocrine therapy alone in women aged 70 years or over and who are fit for
      surgery. OBJECTIVES: To identify and review the evidence from randomised trials
      comparing primary endocrine therapy (endocrine therapy alone) to surgery, with or
      without adjuvant endocrine therapy, in the management of women aged 70 years or
      over with operable breast cancer. SEARCH STRATEGY: The Cochrane Breast Cancer
      Group Specialised Register was searched on 21st August 2003 using the codes for
      "early breast cancer", "endocrine therapy", "psychosocial" or "surgery". Details
      of the search strategy applied to create the register and the procedure used to
      code references are described in the Cochrane Breast Cancer Group module on The
      Cochrane Library. SELECTION CRITERIA: Randomised trials comparing primary
      endocrine therapy with surgery, with or without adjuvant endocrine therapy, in
      the management of women aged 70 years or over with early breast cancer and who
      are fit for surgery. DATA COLLECTION AND ANALYSIS: Studies were assessed for
      eligibility and quality, and data from published trials were extracted by two
      independent reviewers. Hazard ratios were derived for time-to-event outcomes,
      where possible, and a fixed-effect model was used for meta-analysis. Toxicity and
      quality-of-life data were extracted, where present. Where outcome data were not
      available, trialists were contacted and unpublished data requested. MAIN RESULTS:
      Seven eligible trials were identified of which six had published time-to-event
      data and one was published only in abstract form with no usable data. The quality
      of the allocation concealment was adequate in three studies and unclear in the
      remainder. In each case the endocrine therapy used was tamoxifen.Data, based on
      an estimated 869 deaths in 1571 women, were unable to show a statistically
      significant difference in favour of either surgery or primary endocrine therapy
      in respect of overall survival. However, there was a statistically significant
      difference in terms of progression-free survival, which favoured surgery with or
      without endocrine therapy.The hazard ratios (HR) for overall survival were: 0.98
      (95% confidence interval (CI) 0.74 to 1.30, P value 0.9) for surgery alone versus
      primary endocrine therapy; 0.86 (95% CI 0.73 to 1.00, P value 0.06) for surgery
      plus endocrine therapy versus primary endocrine therapy. The HRs for progression
      free survival were: 0.55 (95% CI 0.39 to 0.77, P value 0.0006) for surgery alone
      versus primary endocrine therapy; 0.65 (95% CI 0.53 to 0.81, P value 0.0001) for
      surgery plus endocrine therapy versus primary endocrine therapy (each comparison
      based on only one trial). Tamoxifen-related adverse effects included hot flushes,
      skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache,
      vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and
      indigestion. Surgery-related adverse effects included paresthesia on the
      ipsilateral arm and lateral thoracic wall in those who had axillary clearance.
      One study suggested that those undergoing surgery suffered more psychosocial
      morbidity at three months postsurgery, although this difference had disappeared
      by two years. AUTHORS' CONCLUSIONS: Primary endocrine therapy should only be
      offered to women with oestrogen receptor (ER) positive tumours who are unfit for
      or who refuse surgery. In a cohort of women with significant co-morbid disease
      and ER-positive tumours it is possible that primary endocrine therapy may be a
      superior option to surgery. Trials are needed to evaluate the clinical
      effectiveness of aromatase inhibitors as primary therapy for an infirm older
      population with ER-positive tumours.

PMID- 16437481
TI  - Endoscopic mucosal resection for early gastric cancer.
AB  - BACKGROUND: The treatment of early gastric cancer (EGC) using an endoscopy,
      namely, endoscopic mucosal resection (EMR), has been adopted for about 20 years,
      but the effectiveness and the safety of the modality are still controversial. The
      quality of these trials has not been assessed systematically. OBJECTIVES: The
      purpose of this review was to compare the effectiveness and the safety of EMR
      with gastrectomy for the treatment of EGC. SEARCH STRATEGY: Searches were
      conducted on the Cochrane Central Register of Controlled Trials - CENTRAL (which
      includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials
      Register) on The Cochrane Library (Issue 1 2005) MEDLINE (1966 to March 2005) and
      EMBASE (1980 to March 2005), CINAHL (1985-March 2005) and CBM (Chinese BioMedical
      Database 1982 -2002). Reference lists from trials selected by electronic
      searching were handsearched to identify further relevant trials. Published
      abstracts from conference proceedings from the United European Gastroenterology
      Week (published in Gut) and Digestive Disease Week (published in
      Gastroenterology) were handsearched. Members of the Cochrane UGPD Group, and
      experts in the field were contacted and asked to provide details of outstanding
      clinical trials and any relevant unpublished materials SELECTION CRITERIA: All
      randomised controlled trials of EGC patients involving a treatment arm of EMR and
      a comparison arm of gastrectomy were to be included, but no RCTs were found. DATA
      COLLECTION AND ANALYSIS: Three reviewers (YP Wang, C Bennett and T Pan)
      independently assessed the eligibility of potential trials and extracted the
      data. MAIN RESULTS: There are no included randomised control trials for the
      systematic review. Available evidence derived from non-randomised controlled
      trials is discussed in the main text of this review. AUTHORS' CONCLUSIONS: There
      is a lack of randomised controlled trials in which EMR is compared with
      gastrectomy for EGC. There is a need for well designed randomised controlled
      trials to determine the effects of EMR compared to gastrectomy.

PMID- 16437482
TI  - Opioids for the management of breakthrough (episodic) pain in cancer patients.
AB  - BACKGROUND: Breakthrough pain is a transient increase in pain intensity over
      background pain. It is a common and distinct component of cancer pain that can
      have a negative impact for both the patient and carers' quality of life.
      Breakthrough pain is usually related to background pain and is typically of rapid
      onset, severe in intensity, and generally self-limiting with an average duration
      of 30 minutes. At present the current approach to managing breakthrough pain is
      using supplemental analgesia (also known as rescue medication) at a dose
      proportional to the total around-the-clock (ATC) opioid dose. OBJECTIVES: This
      review explores and assesses the evidence for the use of opioids in the
      management of breakthrough pain in patients with cancer. SEARCH STRATEGY: MEDLINE
      (1966 to 2005), EMBASE (1980 to 2005), CancerLit (1993 to 2005), CINAHL (1982 to
      2005) and Cochrane databases were searched. Handsearching of medical journals and
      reference from key textbooks was undertaken and drug companies contacted for
      unpublished data. There was no language restriction. Date of most recent search:
      January 2005. SELECTION CRITERIA: Randomized controlled trials of opioids used as
      rescue medication against active or placebo comparator in patients with cancer
      pain were included. Outcome measures sought were reduction in pain intensity
      measured by an appropriate scale, adverse effects, attrition, patient
      satisfaction and quality of life. There were no language restrictions. DATA
      COLLECTION AND ANALYSIS: Eligible studies were selected and examined
      independently by the two reviewers. Full text was retrieved if any uncertainty
      about eligibility remained. Non-English texts were screened. Quality assessment
      and data extraction were conducted using standardised data forms. Drug and
      placebo dose, titration, route and formulation were compared and detail of all
      outcome measures (if available) recorded. MAIN RESULTS: Four studies (393
      participants) met the inclusion criteria, all were concerned with the use of oral
      transmucosal fentanyl citrate (OTFC) in the management of breakthrough pain. Two
      studies examined the titration of OTFC, one study compared OTFC to normal release
      morphine and one study compared OTFC to placebo.OTFC was shown to be an effective
      treatment for breakthrough pain. When compared to placebo and morphine,
      participants gave lower pain intensity scores and higher pain relief scores for
      OTFC at all time points. Global assessment scores also favoured OTFC. AUTHORS'
      CONCLUSIONS: There is evidence that OTFC is an effective treatment in the
      management of breakthrough pain. The randomised trial literature for the
      management of breakthrough pain is small and no trials were found for other
      opioids. Given the importance of this subject, more trials need to be undertaken.

PMID- 16437483
TI  - Strategies to improve adherence and acceptability of hormonal methods for
      contraception.
AB  - BACKGROUND: Worldwide, hormonal contraceptives are among the most popular
      reversible contraceptives in current use. Despite their high theoretical
      effectiveness, typical use results in much lower effectiveness. In large part,
      this disparity reflects difficulties in adherence to the contraceptive regimen
      and low rates for long-term continuation. OBJECTIVES: To determine the
      effectiveness of ancillary techniques to improve adherence to, and continuation
      rates of, hormonal methods of contraception. SEARCH STRATEGY: We searched
      computerized databases for randomized controlled trials (RCTs) comparing client
      provider interventions with standard family planning counseling. Sources included
      CENTRAL, MEDLINE, EMBASE, POPLINE, LILACS, and PsycINFO. SELECTION CRITERIA:
      Randomized controlled trials (RCTs) of an intensive counseling technique or
      client-provider intervention versus routine family planning counseling.
      Interventions included group motivation; structured, peer, or multi-component
      counseling; and intensive reminders of appointments. Outcome measures were
      discontinuation, reasons for discontinuation, number of missed pills and on-time
      injections, and pregnancy. DATA COLLECTION AND ANALYSIS: The primary author
      evaluated all titles and abstracts from the searches to determine eligibility.
      Two authors independently extracted data from the included studies. With RevMan
      4.2, we calculated the odds ratio for all dichotomous outcomes and the weighted
      mean difference for continuous data. The studies were so different that we could
      not conduct a meta-analysis. MAIN RESULTS: We found six RCTs; only one showed a
      statistically significant benefit of the experimental intervention. In that
      trial, women who received repeated, structured information about the injectable
      contraceptive depo-medroxyprogesterone acetate (DMPA) were less likely to have
      discontinued the method by 12 months (OR 0.27; 95% CI 0.16 to 0.44) than were
      women who had routine counseling. The intervention group was also less likely to
      discontinue due to menstrual disturbances. In another study, the intervention
      group was less likely to discontinue due to dissatisfaction with the
      contraceptive method, but overall continuation was not affected. AUTHORS'
      CONCLUSIONS: Most studies to date have shown no benefit of strategies to improve
      adherence and continuation. These trials have important limitations, however. Two
      had small sample sizes, several had high losses to follow-up, and the
      intervention and its intensity varied across the studies. High-quality research
      is a priority, since adherence and continuation are fundamentally important to
      the successful use of hormonal contraceptives.

PMID- 16437484
TI  - Interventions for promoting booster seat use in four to eight year olds traveling
      in motor vehicles.
AB  - BACKGROUND: Public health and traffic safety agencies recommend use of booster
      seats in motor vehicles for children aged four to eight years, and various
      interventions have been implemented to increase their use by individuals who
      transport children in motor vehicles. There is little evidence regarding the
      effectiveness of these interventions, hence the need to examine what works and
      what does not. OBJECTIVES: To assess the effectiveness of interventions intended
      to increase acquisition and use of booster seats in motor vehicles among four to
      eight year olds. SEARCH STRATEGY: We searched the Cochrane Injuries Group's
      Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE
      (January 1966 to April 2005), EMBASE (1980 to April 2005), LILACS, Transport
      Research Databases (1988 to April 2005), Australian Transport Index (1976 to
      April 2005), additional databases and reference lists of relevant articles. We
      also contacted experts in the field. SELECTION CRITERIA: We included randomized
      and controlled before-and-after trials that investigated the effects of
      interventions to promote booster seat use. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial quality and extracted data. Study authors
      were contacted for additional information. MAIN RESULTS: Five studies involving
      3,070 individuals met the criteria for inclusion in the meta-analysis. All
      interventions for promoting use of booster seats among 4 to 8 year olds
      demonstrated a positive effect (relative risk (RR) 1.43; 95% confidence intervals
      (CI) 1.05 to 1.96). Incentives combined with education demonstrated a beneficial
      effect (RR 1.32, 95% CI 1.12 to 1.55; n = 1,898). Distribution of free booster
      seats combined with education also had a beneficial effect (RR 2.34; 95% CI 1.50
      to 3.63; n = 380) as did education-only interventions (RR 1.32; 95% CI 1.16 to
      1.49; n = 563). One study which evaluated enforcement of booster seat law met the
      criteria for inclusion in the meta-analysis, but demonstrated no marked
      beneficial effect. AUTHORS' CONCLUSIONS: Available evidence suggests that
      interventions to increase use of booster seats among children age four to eight
      years are effective. Combining incentives (booster seat discount coupons or gift
      certificates) or distribution of free booster seats with education demonstrated
      marked beneficial outcomes for acquisition and use of booster seats for four to
      eight year olds. There is some evidence of beneficial effect of legislation on
      acquisition and use of booster seats but this was mainly from uncontrolled before
      and-after studies, which did not meet the criteria for inclusion in the meta
      analysis.

PMID- 16437485
TI  - Antidepressants for anorexia nervosa.
AB  - BACKGROUND: Anorexia Nervosa (AN) is an illness characterised by extreme concern
      about body weight and shape, severe self-imposed weight loss, and endocrine
      dysfunction. In spite of its high mortality, morbidity and chronicity, there are
      few intervention studies on the subject. OBJECTIVES: The aim of this review was
      to evaluate the efficacy and acceptability of antidepressant drugs in the
      treatment of acute AN. SEARCH STRATEGY: The strategy comprised of database
      searches of the Cochrane Collaboration Depression, Anxiety and Neurosis
      Controlled Trials Register, MEDLINE (1966 to April 28th, 2005), EMBASE (1980 to
      week 36, 2004), PsycINFO (1969 to August week 5, 2004), handsearching the
      International Journal of Eating Disorders and searching the reference lists of
      all papers selected. Personal letters were sent to researchers in the field
      requesting information on unpublished or in-progress trials. SELECTION CRITERIA:
      All randomised controlled trials of antidepressant treatment for AN patients, as
      defined by the Diagnostic and Statistical Manual, fourth edition (DSM-IV) or
      similar international criteria, were selected. DATA COLLECTION AND ANALYSIS:
      Quality ratings were made giving consideration to the strong relationship between
      allocation concealment and potential for bias in the results; studies meeting
      criteria A and B were included. Trials were excluded if non-completion rates were
      above 50%. The standardised mean difference and relative risk were used for
      continuous data and dichotomous data comparisons, respectively. Whenever
      possible, analyses were performed according to intention-to-treat principles.
      Heterogeneity was tested with the I-squared statistic. Weight change was the
      primary outcome. Secondary outcomes were severity of eating disorder, depression
      and anxiety symptoms, and global clinical state. Acceptability of treatment was
      evaluated by considering non-completion rates. MAIN RESULTS: Only seven studies
      were included. Major methodological limitations such as small trial size and
      large confidence intervals decreased the power of the studies to detect
      differences between treatments, and meta-analysis of data was not possible for
      the majority of outcomes. Four placebo-controlled trials did not find evidence
      that antidepressants improved weight gain, eating disorder or associated
      psychopathology. Isolated findings, favouring amineptine and nortriptyline,
      emerged from the antidepressant versus antidepressant comparisons, but cannot be
      conceived as evidence of efficacy of a specific drug or class of antidepressant
      in light of the findings from the placebo comparisons. Non-completion rates were
      similar between the compared groups. AUTHORS' CONCLUSIONS: A lack of quality
      information precludes us from drawing definite conclusions or recommendations on
      the use of antidepressants in acute AN. Future studies testing safer and more
      tolerable antidepressants in larger, well designed trials are needed to provide
      guidance for clinical practice.

PMID- 16437486
TI  - Treatment for mitochondrial disorders.
AB  - BACKGROUND: Mitochondrial respiratory chain disorders are the most prevalent
      group of inherited neurometabolic diseases. They present with central and
      peripheral neurological features usually in association with other organ
      involvement including the eye, the heart, the liver, and kidneys, diabetes
      mellitus and sensorineural deafness. Current treatment is largely supportive and
      the disorders progress relentlessly causing significant morbidity and premature
      death. Vitamin supplements, pharmacological agents and exercise therapy have been
      used in isolated cases and small clinical trials, but the efficacy of these
      interventions is unclear. OBJECTIVES: To determine whether there is objective
      evidence to support the use of current treatments for mitochondrial disease.
      SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials
      register (searched September 2003), the Cochrane Central Register of Controlled
      Trials, MEDLINE (January 1966 to October 3 2003), EMBASE (January 1980 to October
      3 2003) and the European Neuromuscular Centre (ENMC) clinical trials register,
      and contacted experts in the field. SELECTION CRITERIA: We included randomised
      controlled trials (including crossover studies) and quasi-randomised trials
      comparing pharmacological treatments, and non-pharmacological treatments
      (vitamins and food supplements), and physical training in individuals with
      mitochondrial disorders. The primary outcome measures included an improvement in
      muscle strength and/or endurance, or neurological clinical features. Secondary
      outcome measures included quality of life assessments, biochemical markers of
      disease and negative outcomes. DATA COLLECTION AND ANALYSIS: Details of the
      number of randomised patients, treatment, study design, study category,
      allocation concealment and patient characteristics were extracted. Analysis was
      based on intention to treat data. We planned to use meta-analysis, but this did
      not prove necessary. MAIN RESULTS: Six hundred and seventy-eight abstracts were
      reviewed, and six fulfilled the entry criteria. Two trials studied the effects of
      co-enzyme Q10 (ubiquinone), one reporting a subjective improvement and a
      significant increase in a global scale of muscle strength, but the other trial
      did not show any benefit. Two trials used creatine, with one reporting improved
      measures of muscle strength and post-exercise lactate, but the other reported no
      benefit. One trial of dichloroacetate showed an improvement in secondary outcome
      measures of mitochondrial metabolism, and one trial using dimethylglycine showed
      no significant effect. AUTHORS' CONCLUSIONS: There is currently no clear evidence
      supporting the use of any intervention in mitochondrial disorders. Further
      research is needed to establish the role of a wide range of therapeutic
      approaches.

PMID- 16437487
TI  - Psychological interventions for multiple sclerosis.
AB  - BACKGROUND: The unpredictable, variable nature of Multiple Sclerosis (MS), and
      the possibility of increasing disability, means that a diagnosis can have
      substantial psychological consequences. OBJECTIVES: To assess the effectiveness
      of psychological interventions for people with MS. SEARCH STRATEGY: We searched
      19 databases up to December 2004; Cochrane MS Group Specialised Register,
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsychINFO,
      CINAHL and 14 others. We searched reference lists of articles, wrote to
      corresponding authors of the 13 papers identified by June 2004, and searched for
      trials in progress using 3 research registers. SELECTION CRITERIA: Randomised
      controlled trials of interventions described as wholly or mostly based on
      psychological theory and practice, in people with MS. Primary outcome measures
      were disease specific and general quality of life, psychiatric symptoms,
      psychological functioning, disability, and cognitive outcomes. Secondary outcome
      measures were number of relapses, pain, fatigue, health care utilisation, changes
      in medication, and adherence to other therapies. DATA COLLECTION AND ANALYSIS:
      Pertinent studies were identified from abstracts by one author. Full papers were
      independently compared to selection criteria by four authors. Key details were
      extracted from relevant papers using a standard format, and studies scored on
      three dimensions of quality. The review is organised into four mini-reviews (MR)
      dependent on the intervention's target population; people with cognitive
      impairments (MR1), people with moderate to severe disability (MR2), people with
      MS (no other criteria) (MR3), and people with depression (MR4). MAIN RESULTS:
      Overall 16 studies were identified and included. MR1: three trials (n=145). Some
      evidence of effectiveness of cognitive rehabilitation on cognitive outcomes,
      although this was difficult to interpret because of the large number of outcome
      measures used. MR2: three trials (n=80). One small trial suggesting psychotherapy
      may help with depression. MR3: seven studies (n=688). Some evidence that
      cognitive behavioural therapy may help people adjust to, and cope with, having MS
      (three trials). The other trials were diverse in nature and some difficult to
      interpret because of multiple outcome measures. MR4: three trials (n=93). Two
      small studies of cognitive behavioural therapy showed significant improvements in
      depression. AUTHORS' CONCLUSIONS: The diversity of psychological interventions
      identified indicates the many ways in which they can potentially help people with
      MS. No definite conclusions can be made from this review. However there is
      reasonable evidence that cognitive behavioural approaches are beneficial in the
      treatment of depression, and in helping people adjust to, and cope with, having
      MS.

PMID- 16437488
TI  - Oral appliances for obstructive sleep apnoea.
AB  - BACKGROUND: Obstructive sleep apnoea-hypopnoea (OSAH) is a syndrome characterised
      by recurrent episodes of partial or complete upper airway obstruction during
      sleep that are usually terminated by an arousal. Nasal continuous positive airway
      pressure (CPAP) is the primary treatment for OSAH , but many patients are unable
      or unwilling to comply with this treatment. Oral appliances (OA) are an
      alternative treatment for OSAH. OBJECTIVES: The objective was to review the
      effects of OA in the treatment of OSAH in adults. SEARCH STRATEGY: We searched
      the Cochrane Airways Group Specialised Register. Searches were current as of June
      2005. Reference lists of articles were also searched. SELECTION CRITERIA:
      Randomised trials comparing OA with control or other treatments in adults with
      OSAH . DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and
      assessed trial quality. Study authors were contacted for missing information.
      MAIN RESULTS: Sixteen studies (745 participants) met the inclusion criteria. All
      the studies had some shortcomings, such as small sample size, under-reporting of
      methods and data, and lack of blinding. OA versus control appliances (six
      studies): OA reduced daytime sleepiness in two crossover trials (WMD -1.81;95%CI 
      2.72 to -0.90), and improved apnoea-hypopnoea index (AHI) (-10.78; 95% CI-15.53
      to -6.03 parallel group data - five studies). OA versus CPAP (nine studies): OA
      were less effective than CPAP in reducing apnoea-hypopnoea index (parallel group
      studies: WMD 13 (95% CI 7.63 to 18.36), two trials; crossover studies: WMD 7.97;
      (95% CI 6.38 to 9.56, seven trials). However, no significant difference was
      observed on symptom scores. CPAP was more effective at improving minimum arterial
      oxygen saturation during sleep compared with OA. In two small crossover studies,
      participants preferred OA therapy to CPAP. OA versus corrective upper airway
      surgery (one study): Symptoms of daytime sleepiness were initially lower with
      surgery, but this difference disappeared at 12 months. AHI did not differ
      significantly initially, but did so after 12 months in favour of OA. AUTHORS'
      CONCLUSIONS: There is increasing evidence suggesting that OA improves subjective
      sleepiness and sleep disordered breathing compared with a control. CPAP appears
      to be more effective in improving sleep disordered breathing than OA. The
      difference in symptomatic response between these two treatments is not
      significant, although it is not possible to exclude an effect in favour of either
      therapy. Until there is more definitive evidence on the effectiveness of OA in
      relation to CPAP, with regard to symptoms and long-term complications, it would
      appear to be appropriate to recommend OA therapy to patients with mild
      symptomatic OSAH, and those patients who are unwilling or unable to tolerate CPAP
      therapy. Future research should recruit patients with more severe symptoms of
      sleepiness, to establish whether the response to therapy differs between
      subgroups in terms of quality of life, symptoms and persistence with usage. Long
      term data on cardiovascular health are required.

PMID- 16437489
TI  - Routine surgery in addition to chemotherapy for treating spinal tuberculosis.
AB  - BACKGROUND: Tuberculosis is generally curable with chemotherapy, but there is
      controversy in the literature about the need for surgical intervention in the one
      to two per cent of people with tuberculosis of the spine. OBJECTIVES: To compare
      chemotherapy plus surgery with chemotherapy alone for treating people diagnosed
      with active tuberculosis of the spine. SEARCH STRATEGY: We searched the Cochrane
      Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The
      Cochrane Library 2005, Issue 4), MEDLINE (1966 to October 2005), EMBASE (1974 to
      October 2005), LILACS (1982 to October 2005), conference proceedings, and
      reference lists. SELECTION CRITERIA: Randomized controlled trials with at least
      one year follow up that compared chemotherapy plus surgery with chemotherapy
      alone for treating active tuberculosis of the thoracic and/or lumbar spine. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility,
      methodological quality, and extracted data. We analysed data using odds ratio
      with 95% confidence intervals. MAIN RESULTS: Two randomized controlled trials
      (331 participants) met the inclusion criteria. They were conducted in the 1970s
      and 1980s with follow-up reports available after 18 months, three years, and five
      years; one trial also reported 10 years follow up. Completeness of follow up
      varied at the different time points, with less than 80% of participants available
      for analysis at several time points. There was no statistically significant
      difference for any of the outcome measures: kyphosis angle, neurological deficit
      (none went on to develop this), bony fusion, absence of spinal tuberculosis,
      death from any cause, activity level regained, change of allocated treatment, or
      bone loss. Neither trial reported on pain. Of the 130 participants allocated to
      chemotherapy only, 12 had a neurological deficit and five needed a decompression
      operation. One trial suggested that an initial kyphosis angle greater than 30
      degrees is likely to deteriorate, especially in children. AUTHORS' CONCLUSIONS:
      The two included trials had too few participants to be able to say whether
      routine surgery might help. Although current medication and operative techniques
      are now far more advanced, these results indicate that routine surgery cannot be
      recommended unless within the context of a large, well-conducted randomized
      controlled trial. Clinicians may judge that surgery may be clinically indicated
      in some groups of patients. Future studies need to address these topics as well
      as the patient's view of their disease and treatment.

PMID- 16437490
TI  - Perioperative ketamine for acute postoperative pain.
AB  - BACKGROUND: Postoperative pain management is often limited by adverse effects
      such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid
      sparing drug such as ketamine may be of value in giving better analgesia with
      fewer adverse effects. OBJECTIVES: To evaluate the effectiveness and tolerability
      of ketamine administered perioperatively in the treatment of acute postoperative
      pain in adults. SEARCH STRATEGY: Studies were identified from MEDLINE (1966
      2004), EMBASE (1980-2004), the Cochrane Library (2004) and by handsearching
      reference lists from review articles and trials. The manufacturer of ketamine
      (Pfizer) provided search results from their in-house database, PARDLARS.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of adult patients
      undergoing surgery, being treated with perioperative ketamine or placebo. Studies
      where ketamine was administered in addition to a basic analgesic (such as
      morphine or NSAID) in one study group, and compared with a group receiving the
      same basic analgesic (but without ketamine) in another group, were also included.
      DATA COLLECTION AND ANALYSIS: Two independent reviewers identified fifty five
      RCTs for potential inclusion. Quality and validity assessment was performed by
      two independent reviewers. In the case of discrepancy, a third reviewer was
      consulted. Patient reported pain intensity and pain relief was assessed using
      visual analogue scales or verbal rating scales and adverse effects data were
      collated. MAIN RESULTS: Thirty-seven trials were included (2240 participants).
      Eighteen trials were excluded.Twenty-seven of the 37 trials found that
      perioperative subanaesthetic doses of ketamine reduced rescue analgesic
      requirements or pain intensity, or both. Quantitative analysis showed that
      treatment with ketamine reduced 24 hour PCA morphine consumption and
      postoperative nausea or vomiting (PONV). Adverse effects were mild or absent.
      AUTHORS' CONCLUSIONS: Ketamine in subanaesthetic dose (that is a dose which is
      below that required to produce anaesthesia) is effective in reducing morphine
      requirements in the first 24 hours after surgery. Ketamine also reduces
      postoperative nausea and vomiting. Adverse effects are mild or absent.

PMID- 16437491
TI  - Long-term pituitary down-regulation before in vitro fertilization (IVF) for women
      with endometriosis.
AB  - BACKGROUND: Women with endometriosis who are treated with in vitro fertilization
      (IVF) or intracytoplasmic sperm injection (ICSI) have a lower pregnancy rate
      compared to women with tubal factor infertility. It has been suggested that the
      administration of gonadotrophin releasing hormone (GnRH) agonists for a few
      months prior to IVF or ICSI increases the pregnancy rate. OBJECTIVES: To
      determine the effectiveness of administering GnRH agonists for three to six
      months prior to IVF or ICSI in women with endometriosis. SEARCH STRATEGY: We used
      computer searches of the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, the National Research Register (NRR) and the MDSG
      Specialised Register of controlled trials. We handsearched proceedings of annual
      meetings of the American Society for Reproductive Medicine (ASRM) and the
      European Society for Human Reproduction and Embryology (ESHRE). We reviewed lists
      of references in original research and review articles. We contacted experts in
      various countries to identify unpublished trials. SELECTION CRITERIA: We included
      randomised controlled trials using any GnRH agonist prior to IVF or ICSI to treat
      women with any degree of endometriosis diagnosed by laparoscopy or laparotomy
      DATA COLLECTION AND ANALYSIS: Two independent review authors abstracted data (HNS
      and JGV). We sent e-mails to investigators to seek additional information. We
      assessed the validity of each study using the methods suggested in the Cochrane
      Handbook. The data were checked by the third review author (SD) and any
      disagreement was resolved by arbitration with the fourth review author (AA). We
      generated 2 x 2 tables for principal outcome measures. The Peto-modified Mantel
      Haenszel technique was used to calculate odds ratios (OR) and assess statistical
      heterogeneity between studies. MAIN RESULTS: Three randomised controlled trials
      (with 165 women) were included. The live birth rate per woman was significantly
      higher in women receiving the GnRH agonist compared to the control group (OR
      9.19, 95% CI 1.08 to 78.22). However, this was based on one trial reporting
      "viable pregnancy" only. The clinical pregnancy rate per woman was also
      significantly higher (three studies: OR 4.28, 95% CI 2.00 to 9.15). The
      information on miscarriage rates came from two trials with high heterogeneity
      and, therefore, results of the meta-analysis were doubtful. The included studies
      provided insufficient data to investigate the effects of administration of GnRH
      agonists on multiple or ectopic pregnancies, fetal abnormalities or other
      complications. AUTHORS' CONCLUSIONS: The administration of GnRH agonists for a
      period of three to six months prior to IVF or ICSI in women with endometriosis
      increases the odds of clinical pregnancy by fourfold. Data regarding adverse
      effects of this therapy on the mother or fetus are not available at present.

PMID- 16437492
TI  - Voriconazole versus amphotericin B in cancer patients with neutropenia.
AB  - BACKGROUND: Opportunistic fungal infections are a major cause of morbidity and
      mortality in neutropenic cancer patients and antifungal therapy are used both
      empirically and therapeutically in these patients. OBJECTIVES: To compare the
      benefits and harms of voriconazole with those of amphotericin B and fluconazole
      when used for prevention or treatment of invasive fungal infections in cancer
      patients with neutropenia. SEARCH STRATEGY: MEDLINE and the Cochrane Library (May
      2005). Letters, abstracts and unpublished trials were accepted. Contact to
      authors and industry. SELECTION CRITERIA: Randomised trials comparing
      voriconazole with amphotericin B or fluconazole. DATA COLLECTION AND ANALYSIS:
      Data on mortality, invasive fungal infection, colonisation, use of additional
      (escape) antifungal therapy and adverse effects leading to discontinuation of
      therapy were extracted by two authors independently. MAIN RESULTS: Two trials
      were included. One trial compared voriconazole to liposomal amphotericin B as
      empirical treatment of fever of unknown origin (suspected fungal infections) in
      neutropenic cancer patients (849 patients, 58 deaths). The other trial compared
      voriconazole to amphotericin B deoxycholate in the treatment of confirmed and
      presumed invasive Aspergillus infections (391 patients, 98 deaths). In the first
      trial, voriconazole was significantly inferior to liposomal amphotericin B
      according to the authors' prespecified criteria. More patients died in the
      voriconazole group and a claimed significant reduction in the number of
      breakthrough fungal infections disappeared when patients arbitrarily excluded
      from analysis by the authors were included. In the second trial, the deoxycholate
      preparation of amphotericin B was used without any indication of the use of
      premedication and substitution with electrolytes and salt water to avoid
      handicapping this drug. This choice of comparator resulted in a marked difference
      in the duration of treatment on trial drugs (77 days with voriconazole versus 10
      days with amphotericin B), and precludes meaningful comparisons of the benefits
      and harms of the two drugs. AUTHORS' CONCLUSIONS: Liposomal amphotericin B is
      significantly more effective than voriconazole for empirical therapy of
      neutropenic cancer patients and should be preferred. For treatment of
      aspergillosis, there are no trials that have compared voriconazole with
      amphotericin B given under optimal conditions.

PMID- 16437493
TI  - Galantamine for vascular cognitive impairment.
AB  - BACKGROUND: Vascular dementia is the second most common form of dementia.
      Cholinesterase inhibitors modestly improve a broad range of symptoms in some
      patients with Alzheimer's disease through enhancement of cholinergic
      neurotransmission. These drugs may also be beneficial in vascular dementia as
      reductions in acetylcholine and acetyltransferase activity have been reported.
      OBJECTIVES: To assess the efficacy of galantamine in the treatment of people with
      vascular cognitive impairment or vascular dementia or "mixed" dementia. SEARCH
      STRATEGY: Trials were identified from a search of the Specialized Register of the
      Cochrane Dementia and Cognitive Improvement Group on 19 April 2005 using the
      terms: galantamine. galanthamine, reminyl. All major health care databases and
      many ongoing trial databases within the scope of the group are searched regularly
      to keep this Register up to date. SELECTION CRITERIA: All unconfounded randomised
      double-blind trials comparing galantamine with placebo were eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: Two RCTs fulfilling the inclusion
      criteria were included in this review. Two reviewers independently extracted the
      data from these two inclusion studies. MAIN RESULTS: Two trials employing
      randomized, double-blind, parallel-group methodology were included. GAL-INT-6
      reported sub-group data for a pure population of vascular dementia patients
      showing no significant differences in Alzheimer's Disease Assessment Scale
      cognitive subscale (ADAS-cog/11) and Clinician's Interview-based Impression of
      Change (CIBIC-plus) when galantamine was compared against placebo. When data
      combining patients with vascular dementia diagnosed according to recognised
      criteria with a population of patients with Alzheimer's disease and coincidental
      radiographic findings of cerebrovascular disease was analysed, statistically
      significant improvements in cognition (ADAS-cog), global functioning (CIBIC
      plus), activities of daily living (DAD) and behaviour (NPI) were noted. In the
      galantamine treated group, significantly higher numbers of patients dropped out
      and withdrew due to an adverse event. Limited data was available at the time of
      publication for a second larger trial (GAL-INT-26) involving patients with
      vascular dementia diagnosed using standard criteria. Statistically significant
      benefits favouring galantamine over placebo in assessments of cognition (ADAS
      cog/11; p < 0.001) and executive function (Executive Interview, EXIT-25, p =
      0.041) were recorded. No differences in outcome in measures of behaviour
      (Neuropsychiatric Inventory, NPI), daily living (Alzheimer's Disease Cooperative
      Study-Activities of Daily Living inventory, ADCS-ADL) and global functioning
      (CIBIC-plus) in this trial were seen. AUTHORS' CONCLUSIONS: Limited data were
      available when considering the impact of galantamine on vascular dementia or
      vascular cognitive impairment. The data available at the time of review suggest
      some advantage over placebo in the areas of cognition and executive functioning
      in one trial but this was not seen in a second trial which included smaller
      numbers of relevant patients. In both considered trials galantamine produced
      higher rates of gastrointestinal side-effects. More studies are needed before
      firm conclusions can be drawn.

PMID- 16437494
TI  - Cholinesterase inhibitors for Parkinson's disease dementia.
AB  - BACKGROUND: The loss of cholinergic, dopaminergic and noradrenergic innervations
      seen in Parkinson's Disease Dementia (PDD) suggest a potential role for
      cholinesterase inhibitors. Concerns have been expressed about a theoretical
      worsening of Parkinson's disease related symptoms particularly movement symptoms.
      OBJECTIVES: To assess the efficacy, safety, tolerability and health economic data
      relating to the use of cholinesterase inhibitors in PDD. SEARCH STRATEGY: The
      trials were identified from the Specialized Register of the Cochrane Dementia and
      Cognitive Improvement Group on 19 April 2005 using the search term parkinson*This
      register contains records from major health care databases and many ongoing trial
      databases and is updated regularly.Comprehensive searches of abstracts from major
      scientific meetings were performed. Pharmaceutical companies were approached for
      information regarding additional and ongoing studies. SELECTION CRITERIA:
      Randomized, double-blind, placebo-controlled studies assessing the effectiveness
      of cholinesterase inhibitors in PDD. Inclusion and exclusion criteria were stated
      to limit bias. DATA COLLECTION AND ANALYSIS: Two reviewers (IM, CF) independently
      reviewed the quality of the studies utilising criteria from the Cochrane
      Collaboration Handbook. Medications were examined separately and as a group. The
      outcome measures assessed were in the following domains: neuropsychiatric
      features, cognition, global impression, daily living activities, quality of life,
      burden on caregiver, Parkinsonian related symptoms, treatment acceptability as
      determined by withdrawal from trials, safety as determined by the frequency of
      adverse events, institutionalisation, death and health economic factors. MAIN
      RESULTS: A detailed and systematic search of relevant databases identified one
      published randomized, double-blind, placebo-controlled study (Emre 2004)
      involving 541 patients that compared rivastigmine with placebo. Rivastigmine
      produced statistically significant improvements in several outcome measures. On
      the primary cognitive measure, the ADAS-Cog, rivastigmine was associated with a
      2.80 point ADAS-Cog improvement [WMD -2.80, 95% Cl -4.26 to -1.34, P = 0.0002]
      and a 2.50 point ADCS-ADL improvement [95% Cl 0.43 to 4.57, P = 0.02] relative to
      placebo. Clinically meaningful (moderate or marked) improvement occurred in 5.3%
      more patients on rivastigmine, and meaningful worsening occurred in 10.1% more
      patients on placebo. Tolerability appeared to be a significant issue.
      Significantly more patients on rivastigmine dropped out of the study due to
      adverse events [62/362 versus 14/179, OR 2.44, 95% Cl 1.32 to 4.48, P = 0.004].
      Nausea [20/179 versus 105/362, OR 3.25, 95% Cl 1.94 to 5.45, P < 0.00001], tremor
      [7/179 versus 37/362, OR 2.80, 95% Cl 1.22 to 6.41, P = 0.01] and in particular
      vomiting [3/179 versus 60/362, OR 11.66, 95% Cl 3.60 to 37.72, P < 0.0001] were
      significantly more common with rivastigmine. However, significantly fewer
      patients died on rivastigmine than placebo [4/362 versus 7/179, OR 0.27, 95% CI
      0.08 to 0.95, P = 0.04] AUTHORS' CONCLUSIONS: Rivastigmine appears to improve
      cognition and activities of daily living in patients with PDD. This results in
      clinically meaningful benefit in about 15% of cases. There is a need for more
      studies utilising pragmatic measures such as time to residential care facility
      and both patient and carer quality of life assessments. Future trials should
      involve other cholinesterase inhibitors, utilise tools to analyse the data that
      limit any bias and measure health economic factors. It is unlikely that relying
      solely on the last observation carried forward (LOCF) is sufficient. Publication
      of the observed case data in the largest trial would assist (Emre 2004). Adverse
      events were associated with the cholinergic activity of rivastigmine, but may
      limit patient acceptability as evidenced by the high drop out rate in the active
      arm.

PMID- 16437495
TI  - Superficial heat or cold for low back pain.
AB  - BACKGROUND: Heat and cold are commonly utilised in the treatment of low-back pain
      by both health care professionals and people with low-back pain. OBJECTIVES: To
      assess the effects of superficial heat and cold therapy for low-back pain in
      adults. SEARCH STRATEGY: We searched the Cochrane Back Review Group Specialised
      register, the Cochrane Central Register of Controlled Trials (The Cochrane
      Library Issue 3, 2005), MEDLINE (1966 to October 2005), EMBASE (1980 to October
      2005) and other relevant databases. SELECTION CRITERIA: We included randomised
      controlled trials and non-randomised controlled trials that examined superficial
      heat or cold therapies in people with low-back pain. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed methodological quality and extracted
      data, using the criteria recommended by the Cochrane Back Review Group. MAIN
      RESULTS: Nine trials involving 1117 participants were included. In two trials of
      258 participants with a mix of acute and sub-acute low-back pain, heat wrap
      therapy significantly reduced pain after five days (weighted mean difference
      (WMD) 1.06, 95% confidence interval (CI) 0.68 to 1.45, scale range 0 to 5)
      compared to oral placebo. One trial of 90 participants with acute low-back pain
      found that a heated blanket significantly decreased acute low-back pain
      immediately after application (WMD -32.20, 95%CI -38.69 to -25.71, scale range 0
      to 100). One trial of 100 participants with a mix of acute and sub-acute low-back
      pain examined the additional effects of adding exercise to heat wrap, and found
      that it reduced pain after seven days. There is insufficient evidence to evaluate
      the effects of cold for low-back pain, and conflicting evidence for any
      differences between heat and cold for low-back pain. AUTHORS' CONCLUSIONS: The
      evidence base to support the common practice of superficial heat and cold for low
      back pain is limited and there is a need for future higher-quality randomised
      controlled trials. There is moderate evidence in a small number of trials that
      heat wrap therapy provides a small short-term reduction in pain and disability in
      a population with a mix of acute and sub-acute low-back pain, and that the
      addition of exercise further reduces pain and improves function. The evidence for
      the application of cold treatment to low-back pain is even more limited, with
      only three poor quality studies located. No conclusions can be drawn about the
      use of cold for low-back pain. There is conflicting evidence to determine the
      differences between heat and cold for low-back pain.

PMID- 16437496
TI  - Drug treatment for myotonia.
AB  - BACKGROUND: Abnormal delayed relaxation of skeletal muscles, known as myotonia,
      can cause disability in myotonic disorders. Sodium channel blockers, tricyclic
      antidepressive drugs, benzodiazepines, calcium-antagonists, taurine and
      prednisone may be of use in reducing myotonia. OBJECTIVES: To consider the
      evidence from randomised controlled trials on the efficacy and tolerability of
      drug treatment in patients with clinical myotonia due to a myotonic disorder.
      SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials
      register (April 2004), MEDLINE (January 1966 to December 2003) and EMBASE
      (January 1980 to December 2003). Grey literature was handsearched and reference
      lists of identified studies and reviews were examined. Authors, disease experts
      and manufacturers of anti-myotonic drugs were contacted. SELECTION CRITERIA: We
      considered all (quasi) randomised trials of participants with myotonia treated
      with any drug treatment versus no therapy, placebo or any other active drug
      treatment. The primary outcome measure was:reduced clinical myotonia using two
      categories: (1) no residual myotonia or improvement of myotonia or (2) No change
      or worsening of myotonia. Secondary outcome measures were:(1) clinical relaxation
      time; (2) electromyographic relaxation time; (3) stair test; (4) presence of
      percussion myotonia; and (5) proportion of adverse events. DATA COLLECTION AND
      ANALYSIS: Two authors extracted the data independently onto standardised
      extraction forms and disagreements were resolved by discussion. MAIN RESULTS:
      Nine randomised controlled trials were found comparing active drug treatment
      versus placebo or another active drug treatment in patients with myotonia due to
      a myotonic disorder. Included trials were double-blind or single-blind crossover
      studies involving a total of 137 patients of which 109 had myotonic dystrophy
      type 1 and 28 had myotonia congenita. The studies were of poor quality.
      Therefore, we were not able to analyse the results of all identified studies. Two
      small crossover studies without a washout period demonstrated a significant
      effect of imipramine and taurine in myotonic dystrophy. One small crossover study
      with a washout period demonstrated a significant effect of clomipramine in
      myotonic dystrophy. Meta-analysis was not possible. AUTHORS' CONCLUSIONS: Due to
      insufficient good quality data and lack of randomised studies, it is impossible
      to determine whether drug treatment is safe and effective in the treatment of
      myotonia. Small single studies give an indication that clomipramine and
      imipramine have a short-term beneficial effect and that taurine has a long-term
      beneficial effect on myotonia. Larger, well-designed randomised controlled trials
      are needed to assess the efficacy and tolerability of drug treatment for
      myotonia.

PMID- 16437497
TI  - Nicotine for schizophrenia.
AB  - BACKGROUND: The proportion of people with schizophrenia who smoke is very high,
      and as a rule, they tend to be heavier smokers when compared to the general
      population and those with other psychiatric disorders. Nicotine, the psychoactive
      component in tobacco, is thought to produce psychological effects that help to
      alleviate psychotic symptoms. OBJECTIVES: To examine the effects of nicotine and
      related products in the treatment of schizophrenia. SEARCH STRATEGY: We
      electronically searched the Cochrane Schizophrenia Group's Register (April 2005),
      supplemented with manually inspecting references of all identified studies and by
      contacting authors of studies where required. SELECTION CRITERIA: We included all
      randomised clinical trials comparing nicotine or related products as a sole or
      adjunctive treatment for people with schizophrenia or other similar serious, non
      affective psychotic illness. DATA COLLECTION AND ANALYSIS: Citations and, where
      possible, abstracts were independently inspected by reviewers and the papers
      ordered were scrutinised and quality assessed. We extracted and evaluated data
      independently and analysed on an intention to treat basis. We would have
      calculated fixed effect relative risk (RR), number needed to treat/harm (NNT/H)
      and their 95% confidence intervals (CI) for binary outcomes and for continuous
      non-skewed data we would have calculated weighted mean differences. We would have
      excluded data if loss to follow-up had been greater than 50% and inspected the
      data for heterogeneity. MAIN RESULTS: We did not find any trials that met the
      inclusion criteria. AUTHORS' CONCLUSIONS: There ought to be further research of
      nicotine for schizophrenia by parallel group design randomised controlled trials
      investigating the effects of nicotine on symptoms of schizophrenia as well as on
      side effects of antipsychotic drugs. We further note that authors and journals
      should conform to the CONSORT guidelines when publishing the research articles,
      especially when disclosing all the data available from a particular study.

PMID- 16437498
TI  - Surgery versus radiosurgery for patients with a solitary brain metastasis from
      non-small cell lung cancer.
AB  - BACKGROUND: Non-small cell lung cancer is one of the leading causes of death in
      the developed countries. Patients die of local progression, disseminated disease
      or both. Brain metastases are often seen in non-small cell lung cancer patients
      and although they are frequently multiple, a subset of patients with a solitary
      brain metastasis (with controlled primary tumour) is regularly seen in clinical
      practice. Treatment of a solitary brain metastasis has usually been surgery, when
      possible, but the development of new stereotactic techniques of radiotherapy
      using a linear accelerator or the 'gamma knife' have provided new treatment
      options. OBJECTIVES: To compare the effectiveness of surgery with that of
      radiosurgery, either combined with whole brain radiotherapy or administered
      alone, for patients with a solitary brain metastasis from successfully treated
      non-small cell lung cancer. SEARCH STRATEGY: The following electronic databases
      were searched: the Cochrane Central Register of Controlled Trials (CENTRAL, 2004
      issue 2), MEDLINE (1966 to present), EMBASE (1974 to present), CINAHL (1982 to
      present). Finally the Cochrane Lung Cancer Specialised Register was also
      searched. SELECTION CRITERIA: Randomised and controlled trials that compared
      surgery (with or without whole brain irradiation) with all types of radiosurgery
      (with or without whole brain irradiation) for solitary brain metastasis from non
      small cell lung cancer. All other types of studies i.e.prospective or
      retrospective cohort studies were not considered appropriate.Studies including
      patients with multiple brain metastasis or diagnosed without the support of CT
      scan/MRI diagnostic imaging were also excluded. DATA COLLECTION AND ANALYSIS: Two
      review authors independently screened the search results to identify suitable
      trials. MAIN RESULTS: Despite extensive searching no randomised trials were
      found. Electronic search identified 686 references. A total of 47 were selected
      for further evaluation but none was relevant to this review. AUTHORS'
      CONCLUSIONS: The reviewers felt that the inclusion of studies less rigorous than
      randomised trials would result in misleading findings. Cohort or single arm
      studies only provide partial information and have the risk of significant bias.
      From the evaluated studies, we found that a variety of different criteria were
      used for the definition of solitary brain metastasis. We observed that the term
      "single brain metastasis" was misused as synonymous with solitary brain
      metastasis. Some of the single arm or cohort studies come from single
      institutions where the availability of both techniques (radiosurgery and surgery)
      is not described. Therefore, a tendency to use the most accessible technique
      could be suspected. Finally, in order to determine which technique is superior
      for patients with a solitary brain metastasis from non-small cell lung cancer, an
      appropriate randomised trial should be designed. Based on the available evidence
      a meaningful conclusion cannot be drawn.

PMID- 16437499
TI  - Sodium bicarbonate infusion during resuscitation of infants at birth.
AB  - BACKGROUND: For many years, intravenous sodium bicarbonate has been used to
      reverse acidosis during newborn resuscitation. However, controversy surrounds its
      use. Most of the evidence has been derived from studies in animals, adult humans,
      or in uncontrolled, descriptive experiments. Despite the lack of evidence from
      the human neonatal population and concerns about its safety, some international
      resuscitation guidelines still recommend the use of sodium bicarbonate in
      resuscitation of the newborn. OBJECTIVES: To determine whether an intravenous
      infusion of sodium bicarbonate, compared to placebo or no treatment, reduces
      mortality and morbidity (in particular regarding neurodevelopmental outcome) in
      infants receiving resuscitation in the delivery room at birth. SEARCH STRATEGY:
      We used the standard search strategy of the Cochrane Neonatal Review Group.
      Searches were conducted of the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 3, 2005), MEDLINE (1966 - September 2005),
      EMBASE (1980 - September 2005) and CINAHL (1982 - September 2005) and Pediatric
      Research (1987 - September 2005). Unpublished trials were sought by handsearching
      the conference proceedings of American Pediatric Society/Society for Pediatric
      Research (1990 - 2005) and European Society for Paediatric Research (1993 -
      2005). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of
      newborn infants receiving sodium bicarbonate infusion during any resuscitation in
      the delivery room at birth. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. Study authors were
      contacted for additional information. MAIN RESULTS: We found one randomised
      controlled trial that fulfilled the eligibility criteria (Lokesh 2004) that
      compared treating asphyxiated newborn infants (infants continuing to need
      positive pressure ventilation at 5 minutes after birth) with sodium bicarbonate
      infusion (N = 27) versus 5% dextrose (N = 28). They found no evidence of an
      effect on mortality prior to discharge [Relative risk 1.04 (95% confidence
      interval 0.49 to 2.21)], abnormal neurological examination at discharge [Relative
      risk 0.86 (95% confidence interval 0.30 to 2.50)] or a composite outcome of death
      or abnormal neurological examination at discharge [Relative risk 0.97 (95%
      confidence interval 0.59 to 1.60)]. There was no statistically significant
      difference in the incidence of encephalopathy [Relative risk 1.30 (95% confidence
      interval 0.88 to 1.92)], intraventricular haemorrhage [Relative risk 1.04 (95%
      confidence interval 0.23 to 4.70)] and neonatal seizures [Relative risk 1.19 (95%
      confidence interval 0.50 to 2.82)]. No long term neurodevelopmental outcomes were
      assessed. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised
      controlled trials to determine whether the infusion of sodium bicarbonate reduces
      mortality and morbidity in infants receiving resuscitation in the delivery room
      at birth.

PMID- 16437500
TI  - Vaccines for preventing influenza in healthy children.
AB  - BACKGROUND: In children and adults the consequences of influenza are mainly
      absences from school and work, however the risk of complications is greatest in
      children and people over 65 years old. OBJECTIVES: To appraise all comparative
      studies evaluating the effects of influenza vaccines in healthy children; assess
      vaccine efficacy (prevention of confirmed influenza) and effectiveness
      (prevention of influenza-like illness) and document adverse events associated
      with receiving influenza vaccines. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1,
      2005); OLD MEDLINE (1966 to 1969); MEDLINE (1969 to December 2004); EMBASE (1974
      to December 2004); Biological Abstracts (1969 to December 2004); and Science
      Citation Index (1974 to December 2004). We wrote to vaccine manufacturers and a
      number of corresponding authors of studies in the review. SELECTION CRITERIA: Any
      randomised controlled trials (RCTs), cohort and case-control studies of any
      influenza vaccine in healthy children under 16 years old. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial quality and extracted data.
      MAIN RESULTS: Fifty-one studies involving 263,987 children were included.
      Seventeen papers were translated from Russian. Fourteen RCTs and 11 cohort
      studies were included in the analysis of vaccine efficacy and effectiveness. From
      RCTs, live vaccines showed an efficacy of 79% (95% confidence interval (CI) 48%
      to 92%) and an effectiveness of 33% (95% CI 28% to 38%) in children older than
      two years compared with placebo or no intervention. Inactivated vaccines had a
      lower efficacy of 59% (95% CI 41% to 71%) than live vaccines but similar
      effectiveness: 36% (95% CI 24% to 46%). In children under two, the efficacy of
      inactivated vaccine was similar to placebo. Thirty-four reports containing safety
      outcomes were included, 22 including live vaccines, 8 inactivated vaccines and 4
      both types. The most commonly presented short-term outcomes were temperature and
      local reactions. The variability in design of studies and presentation of data
      was such that meta-analysis of safety outcome data was not feasible. AUTHORS'
      CONCLUSIONS: Influenza vaccines are efficacious in children older than two years
      but little evidence is available for children under two. There was a marked
      difference between vaccine efficacy and effectiveness. That no safety comparisons
      could be carried out emphasizes the need for standardisation of methods and
      presentation of vaccine safety data in future studies. It was surprising to find
      only one study of inactivated vaccine in children under two years, given recent
      recommendations to vaccinate healthy children from six months old in the USA and
      Canada. If immunisation in children is to be recommended as public-health policy,
      large-scale studies assessing important outcomes and directly comparing vaccine
      types are urgently required.

PMID- 16437501
TI  - Chinese herbs combined with Western medicine for severe acute respiratory
      syndrome (SARS).
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is an acute respiratory
      disease, which first appeared in Foshan City, China on 22 December 2002. It was
      reported by some that Chinese herbs played an important role in the treatment of
      SARS patients. OBJECTIVES: To evaluate the possible effectiveness and safety of
      Chinese herbs combined with Western medicines versus Western medicines alone for
      SARS patients. SEARCH STRATEGY: We searched the following electronic databases
      for reports of randomised controlled trials: the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005); MEDLINE (1966
      to September 2005); EMBASE (1990 to December 2004); and Chinese Biomedical
      Literature (lssue 2, 2005). SELECTION CRITERIA: Randomized and quasi-randomized
      controlled trials of Chinese herbs combined with Western medicines versus Western
      medicines alone for diagnosed SARS patients were included. DATA COLLECTION AND
      ANALYSIS: Two authors independently extracted the data from each trial. We
      extracted dichotomous and continuous data with 95% confidence intervals (CI). For
      dichotomous data, relative risk (RR) was used. For continuous data, we calculated
      weighted mean differences (WMD). Overall results were calculated based on the
      random effects model if heterogeneity existed between studies. If no
      heterogeneity was detected between the studies, we used the fixed effects model.
      Using the Z score and the chi square statistic with significance being set at p <
      0.05 tested heterogeneity. MAIN RESULTS: We finally included twelve randomized
      controlled trials and one quasi-randomized controlled trial. A total of 654 SARS
      patients and 12 Chinese herbs were identified. We did not find Chinese herbs
      combined with Western medicines decreased morbidity versus Western medicines
      alone. Two herbs may improve symptoms. Five herbs may improve lung infiltrate
      absorption. Four herbs may decrease the dosage of corticosteroids. Three herbs
      may improve the quality of life of SARS patients. One herb may shorten the length
      of stay in hospital. Only two trials reported adverse events. AUTHORS'
      CONCLUSIONS: Chinese herbs combined with Western medicines made no difference in
      decreasing morbidity versus Western medicines alone. It is possible that Chinese
      herbs combined with Western medicines may improve symptoms, quality of life, and
      lung infiltrate absorption and decrease the corticosteroid dosage for SARS
      patients. The evidence is weak because of the poor quality of the included
      trials. Long-term of follow up of these included trials is needed.

PMID- 16437502
TI  - Antibiotic prophylaxis for preventing meningitis in patients with basilar skull
      fractures.
AB  - BACKGROUND: Basilar skull fractures (BSF) predispose patients to meningitis
      because of the possible direct contact of bacteria in the paranasal sinuses,
      nasopharynx or middle ear with the central nervous system (CNS). Cerebrospinal
      fluid (CSF) leakage has been associated with a greater risk of contracting
      meningitis. Antibiotics are often given prophylactically, although their role for
      preventing bacterial meningitis is not established. OBJECTIVES: To evaluate the
      effectiveness of prophylactic antibiotics for preventing meningitis in patients
      with BSF. SEARCH STRATEGY: We searched the Cochrane Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2005),
      EMBASE (1974 to June 2005), and LILACS (1982 to September 2005). We also
      performed an electronic search of meeting proceedings from the American
      Association of Neurological Surgeons (1997 to September 2005) and handsearched
      the abstracts of meeting proceedings of the European Association of Neurosurgical
      Societies (1995, 1999 and 2003). SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing any antibiotic versus placebo or no intervention. We also
      identified non-RCTs to perform a separate meta-analysis to compare results. DATA
      COLLECTION AND ANALYSIS: At least two authors independently appraised the quality
      and extracted the data of each trial. MAIN RESULTS: Five RCTs and 17 non-RCTs
      comparing different types of antibiotic prophylaxis with placebo or no
      intervention in patients with BSF were identified. Most trials presented
      insufficient methodological detail. All studies included meningitis in their
      primary outcome. Overall, we evaluated 208 participants from the four RCTs that
      were considered suitable for inclusion in the meta-analysis. There were no
      significant differences between antibiotic prophylaxis groups and control groups
      in terms of reduction of the frequency of meningitis, all-cause mortality,
      meningitis-related mortality, and need for surgical correction in patients with
      CSF leakage. We performed a subgroup analysis to evaluate the primary outcome in
      patients with and without CSF leakage. We also completed a meta-analysis of all
      the identified controlled non-RCTs (enrolling a total of 2168 patients),
      producing results consistent with the randomised data. AUTHORS' CONCLUSIONS:
      Currently available evidence from RCTs does not support prophylactic antibiotic
      use in patients with BSF, whether there is evidence of CSF leakage or not. Until
      more research is completed, the effectiveness of antibiotics in patients with BSF
      cannot be determined because studies published to date are flawed by biases.
      Large, appropriately designed RCTs are needed.

PMID- 16437503
TI  - Pneumococcal vaccination during pregnancy for preventing infant infection.
AB  - BACKGROUND: Each year at least one million children worldwide die of pneumococcal
      infections. The development of bacterial resistance to antimicrobials adds to the
      difficulty of treatment of diseases and emphasizes the need for a preventive
      approach. Newborn vaccination schedules could substantially reduce the impact of
      pneumococcal disease in immunized children, but does not have an effect on the
      morbidity and mortality of infants less than three months of age. Pneumococcal
      vaccination during pregnancy may be a way of preventing pneumococcal disease
      during the first months of life before the pneumococcal vaccine administered to
      the infant starts to produce protection. OBJECTIVES: To assess the effect of
      pneumococcal vaccination during pregnancy for preventing infant infection. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register
      (June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966
      to June 2004), EMBASE (January 1985 to June 2004), and reference lists of
      articles. SELECTION CRITERIA: Randomized controlled trials in pregnant women
      comparing pneumococcal vaccine with placebo or doing nothing or with another
      vaccine to prevent infant infections. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed methodological quality and extracted data using a data
      collection form. Study authors were contacted for additional information. MAIN
      RESULTS: Three trials (280 participants) were included. There was no evidence
      that pneumococcal vaccination during pregnancy reduces the risk of neonatal
      infection (one trial, 149 pregnancies, relative risk (RR) 0.51; 95% confidence
      interval (CI) 0.18 to 1.41). Although the data suggest an effect in reducing
      pneumococcal colonisation in infants by 16 months of age (one trial, 56
      pregnancies, RR 0.33; 95% CI 0.11 to 0.98), there was no evidence of this effect
      in infants at two months of age (RR 0.28; 95% CI 0.02 to 5.11) or by seven months
      of age (RR 0.32; 95% CI 0.08 to 1.29). AUTHORS' CONCLUSIONS: There is
      insufficient evidence to support whether pneumococcal vaccination during
      pregnancy could reduce infant infections.

PMID- 16437504
TI  - Antifungal agents for preventing fungal infections in non-neutropenic critically
      ill patients.
AB  - BACKGROUND: Invasive fungal infections, important causes of morbidity and
      mortality in critically ill patients, may be preventable with the prophylactic
      administration of antifungal agents. OBJECTIVES: This study aims to
      systematically identify and summarize the effects of antifungal prophylaxis in
      non-neutropenic critically ill adult patients on all-cause mortality and the
      incidence of invasive fungal infections. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library,
      Issue 3, 2005), MEDLINE (1966 to 2 September 2005), and EMBASE (1980 to week 36,
      2005). We also handsearched reference lists, abstracts of conference proceedings
      and scientific meetings (1998 to 2004), and contacted authors of included studies
      and pharmaceutical manufacturers. SELECTION CRITERIA: We included randomized
      controlled trials in all languages comparing the prophylactic use of any
      antifungal agent or regimen with placebo, no antifungal, or another antifungal
      agent or regimen in non-neutropenic critically ill adult patients. DATA
      COLLECTION AND ANALYSIS: Two authors independently applied selection criteria,
      performed quality assessment, and extracted data using an intention-to-treat
      approach. We resolved differences by discussion. We synthesized data using the
      random effects model and expressed results as relative risk with 95% confidence
      intervals. MAIN RESULTS: We included 12 unique trials (eight comparing
      fluconazole and four ketoconazole with no antifungal or a nonabsorbable agent)
      involving 1606 randomized patients. For both outcomes of total mortality and
      invasive fungal infections, almost all trials of fluconazole and ketoconazole
      separately showed a non-significant risk reduction with prophylaxis. When
      combined, fluconazole/ketoconazole reduced total mortality by about 25% (relative
      risk 0.76, 95% confidence interval 0.59 to 0.97) and invasive fungal infections
      by about 50% (relative risk 0.46, 95% confidence interval 0.31 to 0.68). We
      identified no significant increase in the incidence of infection or colonization
      with the azole-resistant fungal pathogens Candida glabrata or C. krusei, although
      the confidence intervals of the summary effect measures were wide. Adverse
      effects were not more common amongst patients receiving prophylaxis. Results
      across all trials were homogeneous despite considerable heterogeneity in clinical
      and methodological characteristics. AUTHORS' CONCLUSIONS: Prophylaxis with
      fluconazole or ketoconazole in critically ill patients reduces invasive fungal
      infections by one half and total mortality by one quarter. Although no
      significant increase in azole-resistant Candida species associated with
      prophylaxis was demonstrated, trials were not powered to exclude such an effect.
      In patients at increased risk of invasive fungal infections, antifungal
      prophylaxis with fluconazole should be considered.

PMID- 16437505
TI  - Prenatal administration of progesterone for preventing preterm birth.
AB  - BACKGROUND: Preterm birth is the major complication of pregnancy associated with
      perinatal mortality and morbidity and occurs in up to 6% to 10% of all births.
      Administration of progesterone for the prevention of preterm labour has been
      advocated. OBJECTIVES: To assess the benefits and harms of progesterone
      administration during pregnancy in the prevention of preterm birth. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Specialised
      Register of Controlled Trials (March 2005), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to January
      2005), EMBASE (1988 to August 2004), and Current Contents (1997 to August 2004).
      SELECTION CRITERIA: All published and unpublished randomised controlled trials,
      in which progesterone was given by any route for preventing preterm birth. DATA
      COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and the
      Cochrane Pregnancy and Childbirth Group were used. Evaluation of methodological
      quality and trial data extraction were undertaken independently by two authors.
      Results are presented using relative risk with 95% confidence intervals. MAIN
      RESULTS: For all women administered progesterone, there was a reduction in the
      risk of preterm birth less than 37 weeks (six studies, 988 participants, relative
      risk (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.79) and preterm birth less
      than 34 weeks (one study, 142 participants, RR 0.15, 95% CI 0.04 to 0.64).
      Infants born to mothers administered progesterone were less likely to have
      birthweight less than 2500 grams (four studies, 763 infants, RR 0.63, 95% CI 0.49
      to 0.81) or intraventricular haemorrhage (one study, 458 infants, RR 0.25, 95% CI
      0.08 to 0.82). There was no difference in perinatal death between women
      administered progesterone and those administered placebo (five studies, 921
      participants, RR 0.66, 95% CI 0.37 to 1.19). There were no other differences
      reported for maternal or neonatal outcomes. AUTHORS' CONCLUSIONS: Intramuscular
      progesterone is associated with a reduction in the risk of preterm birth less
      than 37 weeks' gestation, and infant birthweight less than 2500 grams. However,
      other important maternal and infant outcomes have been poorly reported to date,
      with most outcomes reported from a single trial only (Meis 2003). It is unclear
      if the prolongation of gestation translates into improved maternal and longer
      term infant health outcomes. Similarly, information regarding the potential harms
      of progesterone therapy to prevent preterm birth is limited. Further information
      is required about the use of vaginal progesterone in the prevention of preterm
      birth.

PMID- 16437506
TI  - Conservative management following closed reduction of traumatic anterior
      dislocation of the shoulder.
AB  - BACKGROUND: Acute anterior dislocation is the commonest type of shoulder
      dislocation and usually results from an injury. Subsequently, the shoulder is
      less stable and more susceptible to redislocation, especially in active young
      adults. OBJECTIVES: To compare methods of conservative (non-surgical) management
      versus no treatment or different methods of conservative management after closed
      reduction of traumatic anterior dislocation of the shoulder. Interventions
      include methods of postreduction immobilisation and rehabilitation. SEARCH
      STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group
      Specialised Register (March 2005), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library Issue 3, 2005), MEDLINE, EMBASE, the National
      Research Register (UK), conference proceedings and reference lists of articles.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing
      various conservative interventions versus control (no or sham treatment) or other
      conservative interventions applied after closed reduction of traumatic anterior
      dislocation of the shoulder. DATA COLLECTION AND ANALYSIS: All authors selected
      trials, assessed methodological quality and extracted data. Study authors were
      contacted for additional information. MAIN RESULTS: One flawed quasi-randomised
      trial was included. A "preliminary report" gave the results for 40 adults with
      primary traumatic anterior dislocation of the shoulder treated by post-reduction
      immobilisation with the arm in either external or internal rotation. There was no
      statistically significant difference between the two groups in the failure to
      return to pre-injury sports by previously active athletes, in redislocation or
      shoulder instability. Similar numbers of participants of the two groups removed
      their immobiliser before one week had passed. AUTHORS' CONCLUSIONS: There is a
      lack of evidence from randomised controlled trials to inform the choices for
      conservative management following closed reduction of traumatic anterior
      dislocation of the shoulder. Sufficiently powered, good quality, well reported
      randomised controlled trials with long-term surveillance of conservative
      management are required. In particular, trials examining the type and duration of
      immobilisation would be useful.

PMID- 16437507
TI  - Sulfadoxine-pyrimethamine plus artesunate versus sulfadoxine-pyrimethamine plus
      amodiaquine for treating uncomplicated malaria.
AB  - BACKGROUND: Artemisinin-based combination treatments are strongly advocated, but
      supplies are limited. Sulfadoxine combined with amodiaquine is an alternative non
      artemisinin combination. OBJECTIVES: To compare sulfadoxine-pyrimethamine plus
      amodiaquine (SP plus AQ) with sulfadoxine-pyrimethamine plus artesunate (SP plus
      AS) for treating uncomplicated Plasmodium falciparum malaria. SEARCH STRATEGY: We
      searched the Cochrane Infectious Diseases Group Specialized Register (October
      2005), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to October
      2005), EMBASE (1988 to October 2005), LILACS (October 2005), and reference lists.
      We also contacted researchers and organizations working in this field. SELECTION
      CRITERIA: Randomized controlled trials comparing SP plus AS with SP plus AQ for
      treating uncomplicated P. falciparum malaria. DATA COLLECTION AND ANALYSIS: Two
      authors independently applied the inclusion criteria, extracted data, and
      assessed methodological quality. The primary outcome measure was treatment
      failure (parasitological or clinical evidence of treatment failure between start
      of treatment and day 28). We calculated the relative risk (RR) with 95%
      confidence intervals (CI) for dichotomous data. MAIN RESULTS: Four trials (775
      participants) met the inclusion criteria. All were from areas of high and
      seasonal malaria transmission in Africa. Fewer participants using SP plus AQ
      failed treatment by day 28 (RR 0.59, 95% CI 0.42 to 0.83; 652 participants, 3
      trials). Even excluding new infections, SP plus AQ performed better (RR 0.62, 95%
      CI 0.40 to 0.96; 649 participants, 3 trials). There was no statistically
      significant difference between the two treatments for treatment failure at day 14
      (RR 1.14, 95% CI 0.47 to 2.78; 775 participants, 4 trials). SP plus AS was more
      effective at reducing gametocyte carriage at day seven (RR 2.31, 95% CI 1.36 to
      3.92; 220 participants, 1 trial). One trial reported that one person - in the SP
      plus AQ group - developed severe malaria. Adverse events were poorly reported,
      but did not seem to differ in type and number between the two treatment
      combinations. AUTHORS' CONCLUSIONS: SP plus AQ performed better at controlling
      treatment failure at day 28, but was not as good as SP plus AS at reducing
      gametocyte carriage at day seven. Careful consideration of local resistance
      patterns is required because resistance to sulfadoxine-pyrimethamine and
      amodiaquine are high in many areas. In order to delay development of resistance
      to artesunate, the combination with sulfadoxine-pyrimethamine should only be
      considered where both drugs are known to be effective. Data on adverse events are
      still lacking.

PMID- 16437508
TI  - Surgery versus non-surgical treatment for femoral pseudoaneurysms.
AB  - BACKGROUND: Femoral pseudoaneurysms may complicate up to 8% of vascular
      interventional procedures. Small pseudoaneurysms can spontaneously clot, while
      others need definitive treatment. Surgery is considered the gold-standard
      treatment, although is not without risk in patients with severe cardiovascular
      disease. Less invasive treatment options, such as Duplex ultrasound-guided
      compression and percutaneous thrombin injection are available, however, evidence
      of their efficacy is limited. OBJECTIVES: To assess the effects of different
      treatments for femoral pseudoaneurysms resulting from endovascular procedures,
      specifically assessing less invasive treatment options such as ultrasound-guided
      compression or percutaneous thrombin injection. SEARCH STRATEGY: We searched the
      Cochrane Peripheral Vascular Diseases Review Group's Specialised Register and the
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library
      Issue 3, 2005 (last searched October 12, 2005). Additional searches were also
      made of bibliographies of papers found through these searches and by
      handsearching relevant journals. SELECTION CRITERIA: Randomised controlled trials
      comparing two treatments for femoral pseudoaneurysms following vascular
      interventional procedures were considered for inclusion in the review. DATA
      COLLECTION AND ANALYSIS: Two studies were included in the analysis: ultrasound
      guided application of a mechanical device (FemoStop) versus blind application;
      ultrasound-guided compression versus percutaneous thrombin injection. Data were
      extracted independently by both authors. MAIN RESULTS: Mechanical compression
      with a FemoStop was effective in achieving thrombosis of the pseudoaneurysm
      although ultrasound-guided application of this failed to confer any benefit
      (relative risk (RR) 1.07; 95% confidence intervals (CI) 0.75 to 1.53, P = 0.7).
      Percutaneous thrombin injection was more effective than ultrasound-guided
      compression in achieving thrombosis of a pseudoaneurysm (RR 7.50; 95% CI 2.06 to
      27.25, P = 0.002 at 24 hours after treatment; RR 2.50; 95% CI 1.35 to 4.65, P =
      0.004 at 48 hours after treatment). There was no statistically significant
      difference in the length of hospital stay between the two groups and no
      complications were reported. AUTHORS' CONCLUSIONS: The limited evidence base
      appears to support the use of thrombin injection as an effective treatment for
      femoral pseudoaneurysm. A pragmatic approach may be to use ultrasound-guided
      compression as first-line treatment, reserving thrombin injection for those in
      whom the procedure fails.

PMID- 16437509
TI  - Meditation therapy for anxiety disorders.
AB  - BACKGROUND: Anxiety disorders are characterised by long term worry, tension,
      nervousness, fidgeting and symptoms of autonomic system hyperactivity. Meditation
      is an age-old self regulatory strategy which is gaining more interest in mental
      health and psychiatry. Meditation can reduce arousal state and may ameliorate
      anxiety symptoms in various anxiety conditions. OBJECTIVES: To investigate the
      effectiveness of meditation therapy in treating anxiety disorders SEARCH
      STRATEGY: Electronic databases searched include CCDANCTR-Studies and CCDANCTR
      References, complementary and alternative medicine specific databases, Science
      Citation Index, Health Services/Technology Assessment Text database, and grey
      literature databases. Conference proceedings, book chapters and references were
      checked. Study authors and experts from religious/spiritual organisations were
      contacted. SELECTION CRITERIA: Types of studies: Randomised controlled trials.
      TYPES OF PARTICIPANTS: patients with a diagnosis of anxiety disorders, with or
      without another comorbid psychiatric condition. Types of interventions:
      concentrative meditation or mindfulness meditation. Comparison conditions: one or
      combination of 1) pharmacological therapy 2) other psychological treatment 3)
      other methods of meditation 4) no intervention or waiting list. Types of outcome:
      1) improvement in clinical anxiety scale 2) improvement in anxiety level
      specified by triallists, or global improvement 3) acceptability of treatment,
      adverse effects 4) dropout. DATA COLLECTION AND ANALYSIS: Data were independently
      extracted by two reviewers using a pre-designed data collection form. Any
      disagreements were discussed with a third reviewer, and the authors of the
      studies were contacted for further information. MAIN RESULTS: Two randomised
      controlled studies were eligible for inclusion in the review. Both studies were
      of moderate quality and used active control comparisons (another type of
      meditation, relaxation, biofeedback). Anti-anxiety drugs were used as standard
      treatment. The duration of trials ranged from 3 months (12 weeks) to 18 weeks. In
      one study transcendental meditation showed a reduction in anxiety symptoms and
      electromyography score comparable with electromyography-biofeedback and
      relaxation therapy. Another study compared Kundalini Yoga (KY), with
      Relaxation/Mindfulness Meditation. The Yale-Brown Obsessive Compulsive Scale
      showed no statistically significant difference between groups. The overall
      dropout rate in both studies was high (33-44%). Neither study reported on adverse
      effects of meditation. AUTHORS' CONCLUSIONS: The small number of studies included
      in this review do not permit any conclusions to be drawn on the effectiveness of
      meditation therapy for anxiety disorders. Transcendental meditation is comparable
      with other kinds of relaxation therapies in reducing anxiety, and Kundalini Yoga
      did not show significant effectiveness in treating obsessive-compulsive disorders
      compared with Relaxation/Meditation. Drop out rates appear to be high, and
      adverse effects of meditation have not been reported. More trials are needed.

PMID- 16437510
TI  - Reminder packaging for improving adherence to self-administered long-term
      medications.
AB  - BACKGROUND: Current methods of improving medication adherence for health problems
      are mostly complex, labour-intensive, and not reliably effective. Medication
      'reminder packaging' which incorporates a date or time for a medication to be
      taken in the packaging, can act as a reminder system to improve adherence.
      OBJECTIVES: The objective of this review was to determine the effects of reminder
      packaging to enhance patient adherence with self-administered medications taken
      for one month or more. SEARCH STRATEGY: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of
      Effects (DARE) (The Cochrane Library Issue 3, 2004), MEDLINE, EMBASE, CINAHL and
      PsycINFO from the start of the databases to 1 September 2004. We also searched
      the internet, contacted packaging manufacturers, and checked abstracts from the
      Pharm-line database and reference lists from relevant articles. We did not apply
      any language restrictions. SELECTION CRITERIA: We selected randomised controlled
      trials with at least 80% follow up, comparing a reminder packaging device with no
      device in participants taking self-administered medications for a minimum of one
      month. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies
      for inclusion, assessed quality, and extracted data from included studies. Where
      considered appropriate, data were combined for meta-analysis, or were reported
      and discussed in a narrative. MAIN RESULTS: Eight studies containing data on
      1,137 participants were included. Six intervention groups in four trials provided
      data on the percentage of pills taken. Reminder packaging showed a significant
      increase in the percentage of pills taken, weighted mean difference 11% (95%
      confidence interval (CI) 6% to 17%). Notable heterogeneity occurred among these
      trials I(2 )= 96.3%. Two trials provided data for the proportion of self-reported
      adherent patients, reporting a reduction in the intervention group which was not
      statistically significant, odds ratio = 0.89 (95% CI 0.56 to 1.40). No
      appropriate data were available for meta-analysis of different clinical outcomes,
      the most common of these being blood pressure (three out of eight trials). Other
      clinical outcomes reported were glycated haemoglobin, serum Vitamin C and E
      levels, and self-reported psychological symptoms (one trial each). AUTHORS'
      CONCLUSIONS: Reminder packing may represent a simple method for improving
      adherence for patients with selected conditions examined to date. Further
      research is warranted to improve the design and targeting of these devices.

PMID- 16437511
TI  - Interventions for prevention of drug use by young people delivered in non-school
      settings.
AB  - BACKGROUND: Interventions intended to prevent or reduce use of drugs by young
      people may be delivered in schools or in other settings. This review aims to
      summarise the current literature about the effectiveness of interventions
      delivered in non schools settings. OBJECTIVES: (1) - To summarise the current
      evidence about the effectiveness of interventions delivered in non-school
      settings intended to prevent or reduce drug use by young people under 25;(2) - To
      investigate whether interventions' effects are modified by the type and setting
      of the intervention, and the age of young people targeted;(3) - To identify areas
      where more research is needed. SEARCH STRATEGY: We searched Cochrane Central
      Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 4, 2004),
      MEDLINE (1966-2004), EMBASE (1980-2004), PsycInfo (1972-2004), SIGLE (1980-2004),
      CINAHL (1982-2004) and ASSIA (1987-2004). We searched also reference lists of
      review articles and retrieved studies. SELECTION CRITERIA: Randomised trials that
      evaluated an intervention targeting drug use by young people under 25 years of
      age, delivered in a non-school setting, compared with no intervention or another
      intervention, that reported substantive outcomes relevant to the review. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and
      extracted data. Results were tabulated, as studies were considered too dissimilar
      to combine using meta-analysis. MAIN RESULTS: Seventeen studies, 9 cluster
      randomised studies, with 253 clusters, 8 individually randomised studies with
      1230 participants, evaluating four types of intervention: motivational
      interviewing or brief intervention, education or skills training, family
      interventions and multi-component community interventions. Many studies had
      methodological drawbacks, especially high levels of loss to follow-up. There were
      too few studies for firm conclusions. One study of motivational interviewing
      suggested that this intervention was beneficial on cannabis use. Three family
      interventions (Focus on Families, Iowa Strengthening Families Program and
      Preparing for the Drug-Free Years), each evaluated in only one study, suggested
      that they may be beneficial in preventing cannabis use. The studies of multi
      component community interventions did not find any strong effects on drug use
      outcomes, and the two studies of education and skills training did not find any
      differences between the intervention and control groups. AUTHORS' CONCLUSIONS:
      There is a lack of evidence of effectiveness of the included interventions.
      Motivational interviewing and some family interventions may have some benefit.
      Cost-effectiveness has not yet been addressed in any studies, and further
      research is needed to determine whether any of these interventions can be
      recommended.

PMID- 16437512
TI  - Perioperative blood transfusions for the recurrence of colorectal cancer.
AB  - BACKGROUND: The improvement of renal allograft survival by pre-transplantation
      transfusions alerted the medical community to the potential detrimental effect of
      transfusions in patients being treated for cancer. OBJECTIVES: The present meta
      analysis aims to evaluate the role of perioperative blood transfusions (PBT) on
      colorectal cancer recurrence. This is accomplished by validating the results of a
      previously published meta-analysis (Amato 1998); and by updating it to December
      2004. SEARCH STRATEGY: Published papers were retrieved using Medline, EMBASE, the
      Cochrane Library, controlled trials web-based registries, or the CCG Trial
      Database. The search strategy used was: {colon OR rectal OR colorectal} WITH
      {cancer OR tumor OR neoplasm} AND transfusion. The tendency not to publish
      negative trials was balanced by inspecting the proceedings of international
      congresses. SELECTION CRITERIA: Patients undergoing curative resection of
      colorectal cancer (classified either as Dukes stages A-C, Astler-Coller stages A
      C2, or TNM stages T1-3a/N0-1/M0) were included if they had received any amount of
      blood products within one month of surgery. Excluded were patients with distant
      metastases at surgery, and studies with short follow-up or with no data. DATA
      COLLECTION AND ANALYSIS: A specific form was developed for data collection. Data
      extraction was cross-checked, using the most recent publication in case of
      repetitive ones. Papers' quality was ranked using the method by Evans and
      Pollock. Odds ratios (OR, with 95% confidence intervals) were computed for each
      study, and pooled estimates were generated by RevMan (version 4.2). When
      available, data were stratified for risk factors of cancer recurrence. MAIN
      RESULTS: The findings of the 1998 meta-analysis were confirmed, with small
      variations in some estimates. Updating it through December 2004 led to the
      identification of 237 references. Two-hundred and one of them were excluded
      because they analyzed survival (n=22), were repetitive (n=26), letters/reviews
      (n=66) or had no data (n=87). Thirty-six studies on 12,127 patients were
      included: 23 showed a detrimental effect of PBT; 22 used also multivariable
      analyses, and 14 found PBT to be an independent prognostic factor. Pooled
      estimates of PBT effect on colorectal cancer recurrence yielded overall OR of
      1.42 (95% CI, 1.20 to 1.67) against transfused patients in randomized controlled
      studies. Stratified meta-analyses confirmed these findings, also when stratifying
      patients by site and stage of disease. The PBT effect was observed regardless of
      timing, type, and in a dose-related fashion, although heterogeneity was detected.
      Data on surgical techniques was not available for further analysis. AUTHORS'
      CONCLUSIONS: This updated meta-analysis confirms the previous findings. All
      analyses support the hypothesis that PBT have a detrimental effect on the
      recurrence of curable colorectal cancers. However, since heterogeneity was
      detected and conclusions on the effect of surgical technique could not be drawn,
      a causal relationship cannot still be claimed. Carefully restricted indications
      for PBT seems necessary.

PMID- 16437513
TI  - Acid reflux treatment for hoarseness.
AB  - BACKGROUND: Acid reflux is a common problem, and is thought to occur in 4% to 10%
      of patients presenting to ENT clinics. A recent study of reflux and voice
      disorders suggests that up to 55% of patients with hoarseness (dysphonia) have
      laryngopharyngeal reflux. Anti-reflux therapy is often used empirically in
      treating patients with hoarseness, where no other cause has been identified by
      examination. OBJECTIVES: The aim of the review was to assess the effectiveness of
      anti-reflux therapy for patients with hoarseness, in the absence of other
      identifiable causes, whether or not a definitive diagnosis of laryngopharyngeal
      and gastro-oesophageal reflux has been made. This was assessed by evaluation of
      prospective randomised controlled studies that were identified by a systematic
      review of the literature. Both medical and surgical treatments were evaluated.
      SEARCH STRATEGY: The Cochrane ENT Group Specialised Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 3, 2005),
      MEDLINE (1966 to 2005), EMBASE (1974 to 2005) and conference proceedings were
      searched with prespecified terms. The date of the last search was September 2005.
      SELECTION CRITERIA: Randomised controlled trials recruiting patients with
      hoarseness in the absence of other identifiable causes, such as malignancy, cord
      palsy or nodules, whether or not a definitive diagnosis of laryngopharyngeal and
      gastro-oesophageal reflux has been made. DATA COLLECTION AND ANALYSIS: Three
      reviewers examined the search results and identified studies before deciding
      which would be included in the review. MAIN RESULTS: 302 potential studies were
      identified by the search strategy. No trials were identified which met our
      inclusion criteria. Six randomised controlled trials were identified in which
      some, but not all patients presented with hoarseness, and were treated with
      proton pump inhibition. As we could not determine with certainty whether all
      these patients had hoarseness among the other laryngeal symptoms, these were
      excluded. However, these studies suggest a significant placebo response, which is
      comparable to the benefit derived from anti-reflux therapy in some studies. As no
      trials met our criteria, we are unable to reach any firm conclusions regarding
      the effectiveness of anti-reflux treatment for hoarseness. AUTHORS' CONCLUSIONS:
      There is a need for high quality randomised controlled trials to evaluate the
      effectiveness of anti-reflux therapy for patients with hoarseness which may be
      due to laryngopharyngeal and gastro-oesophageal reflux.

PMID- 16437514
TI  - Gonadotrophins for idiopathic male factor subfertility.
AB  - BACKGROUND: Male factor infertility accounts for 50% of infertility. The
      treatment of idiopathic male infertility is empirical. Urinary, purified, and
      recombinant gonadotrophins have been used to improve sperm parameters in
      idiopathic male infertility with the goal of increasing pregnancy rates. Research
      addressing pregnancy rates in partners of men treated with gonadotrophins has had
      conflicting results and needs to be analysed. OBJECTIVES: To determine the
      effectiveness of gonadotrophin administration to men with idiopathic subfertility
      on spontaneous pregnancy rate and in assisted reproductive techniques (ARTs).
      SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility
      Group trials register (19 November 2004), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library, issue 4, 2004), MEDLINE (1966 to April
      2005), EMBASE and Biological Abstracts (1980 to November 2004). Searches were not
      limited by language. The bibliographies of included, excluded trials and
      abstracts of major meetings were searched for additional trials. Authors and
      pharmaceutical companies were contacted for missing and unpublished data.
      SELECTION CRITERIA: Truly randomised controlled trials where gonadotrophins were
      administered for the treatment of idiopathic male subfertility with reporting of
      pregnancy rates were included in the review. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality and extracted data. Study authors
      were contacted for additional information. Adverse effects information was
      collected from the trials. We analysed data regarding pregnancy occurring within
      3 months after gonadotrophin therapy. MAIN RESULTS: Four RCTs with 278
      participant were included in the analysis. None of the studies had an adequate
      sample size and they had variable follow-up periods. None of the studies reported
      live birth or miscarriage rates. Compared to placebo or no treatment,
      gonadotrophins showed a significantly higher pregnancy rate per couple randomized
      within 3 months of completing therapy (OR 3.03, 95% CI 1.30 to 7.09). Pregnancy
      rate was 13.4% (19/142) in the gonadotrophin group and 4.4% (6/136) in the
      control group. AUTHORS' CONCLUSIONS: The number of trials and participants is
      insufficient to draw final conclusions. A large multicenter study with adequate
      power is needed.

PMID- 16437515
TI  - Uterine artery embolization for symptomatic uterine fibroids.
AB  - BACKGROUND: Uterine fibroids cause heavy and prolonged bleeding, pain, pressure
      symptoms and subfertility but are mostly benign. The traditional method of
      treatment has been surgery as long term medical therapies have not shown to be
      effective. Uterine artery embolization (UAE - complete occlusion of both the
      uterine arteries with particulate emboli) has been reported to be an effective
      and safe alternative in the treatment of menorrhagia and other fibroid-related
      symptoms in women not desiring future fertility, but thus far this evidence is
      based on case controlled studies and case reports. OBJECTIVES: To review the
      benefits and/or harms from randomised controlled trials (RCTs) of uterine artery
      embolization (UAE) versus other interventions for symptomatic uterine fibroids.
      SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility
      Group Trials register (searched 10 August 2005), the Cochrane Central Register of
      Controlled Trials (CENTRAL) on the Cochrane Library, Issue 3, 2004), MEDLINE
      (January 1966 to November 2005) and EMBASE (January 1980 to November 2005). We
      also contacted authors of potential ongoing studies. SELECTION CRITERIA: RCTs of
      UAE versus any medical or surgical therapy for symptomatic uterine fibroids. DATA
      COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) assessed the trials and
      extracted the data independently. They also contacted the investigators of
      eligible RCTs for unpublished data. MAIN RESULTS: Three trials were included in
      this review. Two RCTs compared UAE with abdominal hysterectomy in 234 women.
      Although the follow-up period was intended for two years, the available published
      results was only for six months follow-up. The second trial included 63 women
      comparing UAE with myomectomy in women who wished to preserve their fertility.
      The minimum follow-up reported was six months with a mean of 17 (+/- 9.3) months.
      The clinical success rate measured by improvement in fibroid-related symptoms
      e.g. menstrual loss was at least 85% in the UAE group from both trials. The mean
      dominant fibroid volume decreased by 30 to 46% in two trials. UAE significantly
      reduces length of hospital stay compared to surgery for either hysterectomy or
      myomectomy. Women undergoing UAE resumed routine activities sooner than those
      undergoing surgery. UAE was associated with a higher rate of minor post
      procedural complications such as vaginal discharge, post puncture haematoma and
      post embolization syndrome (pain, fever, nausea, vomiting), as well as higher
      unscheduled visits and readmission rates after discharge, compared with
      hysterectomy. There were no major complication differences between the two
      groups. Three women in the myomectomy trial had elevated FSH levels post UAE
      indicating possible ovarian dysfunction. AUTHORS' CONCLUSIONS: UAE offers an
      advantage over hysterectomy with regards to a shorter hospital stay and a quicker
      return to routine activities. There is no evidence of benefit of UAE compared to
      surgery (hysterectomy / myomectomy) for satisfaction. The higher minor
      complications rate after discharge in the UAE group as well as the unscheduled
      visits and readmission rates require more longer term follow-up trials to comment
      on its effectiveness and safety profile. There is currently an ongoing trial
      (REST, U. K.) and EMMY trial yet to report on the long term follow up, the
      results of which are awaited with interest.

PMID- 16437516
TI  - Silver based wound dressings and topical agents for treating diabetic foot
      ulcers.
AB  - BACKGROUND: Foot ulceration affects 15-20% of people with diabetes. It is a major
      precursor to amputation in this patient group, and early and appropriate
      treatment provides the greatest opportunity for healing. The use of silver for
      its antimicrobial properties has re-emerged, and modern wound dressings that
      release a sustained amount of free silver ions, are now widely used in wound
      management. OBJECTIVES: To evaluate the effects of silver-containing dressings
      and topical agents on infection rates and healing of diabetes related foot
      ulcers. SEARCH STRATEGY: Searches were made of the Cochrane Wounds Group
      Specialised Register (August 2005), the Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library Issue 3 2005) MEDLINE (1966 to October week
      2 2004), EMBASE (1980 to October week 2 2004) and CINAHL (1982 to October week 2
      2004). The Journal of Wound Care (Volume 12/13 Issues 1-10) was hand-searched.
      Manufacturers, researchers and local and international wound groups were
      contacted in order to identify unpublished trials. Web sites for wound groups and
      World Wide Wounds (www.worldwidewounds.com) were searched. SELECTION CRITERIA:
      Randomised controlled trials and non-randomised controlled clinical trials were
      considered for inclusion. Studies were included if they involved participants
      with Type 1 or Type 2 diabetes and related foot ulcers, met the requirements for
      randomisation, allocation and concealment where appropriate, and compared the
      intervention with a placebo or a sham dressing, an alternative non silver based
      dressing or no dressing, and reported outcomes that represent healing rate or
      infection. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the
      papers identified by the search strategy against the inclusion criteria but
      identified no trials eligible for inclusion in the review. It was not possible to
      perform planned subgroup and sensitivity analysis in the absence of data. In
      future, if eligible trials become available, a random effects model will be
      applied for meta-analysis in the presence of statistical heterogeneity (estimated
      using the I(2) statistic). Dichotomous outcomes will be reported as risk ratios
      with 95% confidence intervals (CI), and continuous outcomes as weighted mean
      differences (WMD) with 95% CI. Statistical significance will be set at P value <
      0.05 for all outcomes and the magnitude of the effect will be estimated by
      calculating the number needed to treat (NNT) with 95% CI. MAIN RESULTS: No
      studies were identified that met with the inclusion criteria AUTHORS'
      CONCLUSIONS: Despite the widespread use of dressings and topical agents
      containing silver for the treatment of diabetic foot ulcers, no randomised trials
      or controlled clinical trials exist that evaluate their clinical effectiveness.
      Trials are needed to determine clinical and cost-effectiveness and long term
      outcomes including adverse events.

PMID- 16437517
TI  - Interventions for tobacco cessation in the dental setting.
AB  - BACKGROUND: Tobacco use has significant adverse effects on oral health. Oral
      health professionals in the dental office or community setting have a unique
      opportunity to increase tobacco abstinence rates among tobacco users. OBJECTIVES:
      This review assesses the effectiveness of interventions for tobacco cessation
      offered to cigarette smokers and smokeless tobacco users in the dental office or
      community setting. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction
      group Specialized Register (CENTRAL), MEDLINE (1966-2004), EMBASE (1988-2004),
      CINAHL (1982-2004), Healthstar (1975-2004), ERIC (1967-2004), PsycINFO (1984
      2004), National Technical Information Service database (NTIS, 1964-2004),
      Dissertation Abstracts Online (1861-2004), Database of Abstract of Reviews of
      Effectiveness (DARE, 1995-2004), and Web of Science (1993-2004). SELECTION
      CRITERIA: We included randomized and pseudo-randomized clinical trials assessing
      tobacco cessation interventions conducted by oral health professionals in the
      dental office or community setting with at least six months of follow up. DATA
      COLLECTION AND ANALYSIS: Two authors independently reviewed abstracts for
      potential inclusion and abstracted data from included trials. Disagreements were
      resolved by consensus. MAIN RESULTS: Six clinical trials met the criteria for
      inclusion in this review. Included studies assessed the efficacy of interventions
      in the dental office or a school community setting. All studies assessed the
      efficacy of interventions for smokeless tobacco users, one of which included
      cigarettes smokers. All studies employed behavioural interventions and only one
      offered pharmacotherapy as an interventional component. All studies included an
      oral examination component. Pooling of the studies suggested that interventions
      conducted by oral health professionals increase tobacco abstinence rates (odds
      ratio [OR] 1.44; 95% confidence interval [CI]: 1.16 to 1.78) at 12 months or
      longer. Heterogeneity was evident (I(2) = 75%) and could not be adequately
      explained through subgroup or sensitivity analyses. AUTHORS' CONCLUSIONS:
      Available evidence suggests that behavioural interventions for tobacco use
      conducted by oral health professionals incorporating an oral examination
      component in the dental office and community setting may increase tobacco
      abstinence rates among smokeless tobacco users. Differences between the studies
      limit the ability to make conclusive recommendations regarding the intervention
      components that should be incorporated into clinical practice.

PMID- 16437518
TI  - One dose per day compared to multiple doses per day of gentamicin for treatment
      of suspected or proven sepsis in neonates.
AB  - BACKGROUND: Gentamicin is widely used in the treatment of suspected or proven
      neonatal sepsis. Animal studies and systematic reviews from trials in older
      children and adults suggest that a one dose per day regimen is superior to a
      multiple doses per day regimen. Pharmacokinetic studies and retrospective audits
      in neonatal population also favour once a day administration of gentamicin.
      However, there is no consensus regarding the dose interval regimen in the
      neonatal population. OBJECTIVES: To compare the efficacy and safety of one dose
      per day compared to multiple doses per day of gentamicin in suspected or proven
      sepsis in neonates. SEARCH STRATEGY: Eligible studies were identified by
      searching MEDLINE (March 2005), EMBASE 1980 - 2004, Oxford Database of Perinatal
      Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
      Library, Issue 2, 2005) and CINAHL (December 1982 - March 2005). Abstracts of the
      Society for Pediatric Research were hand searched from 1980 to 2004 inclusive. No
      language restrictions were applied. SELECTION CRITERIA: All randomised or quasi
      randomised controlled trials comparing one dose per day ( 'once a day') compared
      to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn
      infants < 28 days of life. DATA COLLECTION AND ANALYSIS: Methodological quality
      of eligible studies was assessed according to allocation concealment, blinding of
      intervention, blinding of outcome assessment and completeness of follow up. Data
      were sought regarding effects on clinical efficacy, pharmacokinetic efficacy,
      ototoxicity and nephrotoxicity of the two regimens. When appropriate, meta
      analysis was conducted to provide a pooled estimate of effect. For categorical
      data, the typical relative risk (RR), typical risk difference (RD) and number
      needed to treat (NNT) with 95% confidence intervals (CI) were calculated.
      Continuous data were analysed using weighted mean difference (WMD). MAIN RESULTS:
      Twenty four studies were initially identified. Thirteen were excluded and eleven
      studies (N = 574) included. All studies compared the effectiveness and safety of
      'once a day' versus 'multiple doses a day' regimen of gentamicin in newborn
      infants. Only one study enrolled infants less than 32 weeks gestation. All except
      one trial used intravenous infusion. One trial used gentamicin as a bolus dose
      over one minute. Two trials used intramuscular gentamicin in some of their study
      infants. For the primary outcome of 'clearance of sepsis', all infants in both
      'once a day' as well as 'multiple doses a day' regimen showed adequate clearance
      of sepsis [Typical RD 0.00 (95% CI - 0.19, 0.19); 3 trials; N = 36]. For the
      other primary outcome measures relating to gentamicin pharmacokinetics, 'once a
      day dosing' of gentamicin was superior. 'Once a day' gentamicin regimen is
      associated with less failures to attain peak level of at least 5 microg/ml
      [Typical RR 0.22 (95% CI 0.11, 0.47); Typical RD -0.13 (95% CI -0.19, -0.08); 9
      trials; N = 422]; less failures to achieve trough levels of < 2 microg/ml
      [Typical RR 0.38 (95% CI 0.27, 0.55); Typical RD -0.22 (95% CI -0.29, -0.15); 11
      trials N = 503]; higher peak levels [WMD 2.58 (95% CI 2.26, 2.89); 10 trials; N =
      440] and lower trough levels [WMD -0.57 (95% CI -0.69, -0.44); 10 trials; N =
      440] compared to 'multiple doses a day' regimen. Ototoxicity and nephrotoxicity
      were not noted with either of the treatment regimens. Significant heterogeneity
      was noted for some of the outcomes measured. Hence the results need to be
      interpreted with caution. Possible reasons for heterogeneity are different
      gestational ages of study infants and the timing of collection of blood samples
      in relation to a particular dose and the day of therapy on which the samples were
      collected. AUTHORS' CONCLUSIONS: There is insufficient evidence from the
      currently available RCTs to conclude whether 'once a day' or 'multiple doses a
      day' regimen of gentamicin is superior in treating proven neonatal sepsis.
      However data suggests that pharmacokinetic properties of 'once a day' gentamicin
      regimen are superior to 'multiple doses a day' regimen in that it achieves higher
      peak levels while avoiding toxic trough levels. There is no change in
      nephrotoxicity or auditory toxicity. Based on this assessment of
      pharmacokinetics, 'once a day regimen' may be superior in treating neonatal
      sepsis in neonates more than 32 weeks gestation.

PMID- 16437519
TI  - Diacerein for osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is one of the most prevalent musculoskeletal
      diseases. Diacerein acts differently from traditional non-steroidal anti
      inflammatory drugs (NSAIDs) which inhibit prostaglandin synthesis, leading to
      adverse gastrointestinal effects. It has been proposed that diacerein acts as a
      slow-acting, symptom-modifying and perhaps disease-structure modifying drug for
      OA. OBJECTIVES: To assess the effectiveness and safety of diacerein for treatment
      of OA in adults with peripheral or axial osteoarthritis according the American
      College of Rheumatology and/or EULAR diagnostic criteria. SEARCH STRATEGY: We
      searched MEDLINE (1966-2004), EMBASE (1980-2004), Cochrane Central Register of
      Controlled Trials (CENTRAL), The Cochrane Library, Issue 3, 2004, and LILACS(1982
      2004) and hand searched reference lists of published articles. Pharmaceutical
      companies and authors of published articles were contacted. There was no language
      restriction. SELECTION CRITERIA: Randomized controlled trials (RCT) or quasi-RCTs
      of placebo-controlled and comparative studies of diacerein in adults with primary
      or secondary OA fulfilling the American College of Rheumatology (ACR) criteria
      were eligible for inclusion. The main criteria for exclusion was evidence of
      secondary disease. DATA COLLECTION AND ANALYSIS: Data abstraction and quality
      assessment was performed independently by three investigators according to
      predetermined criteria and the results were compared to determine the degree of
      agreement. Quality evaluation was done using Cochrane Handbook Criteria, Jadad
      and Schultz scores. Continuous outcome measures were pooled using weighted mean
      differences (WMD). Dichotomous outcome measures were pooled using random effects
      model and results were expressed as relative risks (RR). MAIN RESULTS:
      Collectively, the seven identified studies including 2069 participants
      demonstrated a small, consistent, beneficial effect of diacerein in the treatment
      of OA. When compared to placebo, pain on a visual analog scale (0-100 mm) was
      evaluated in 1228 participants and showed a statistically significant difference
      in favour of diacerein WMD -5.16 (95%CI -9.75, -0.57) with an absolute change of
      5 points on the scale; but the heterogeneity analysis result was important
      (P=0.04). When analysed separately by hip OA and knee OA, no difference was
      detected. According to the Lequesne Impairment Index for function, 1006
      participants evaluated did not have improvement in the whole group or in the
      subgroup analysis with homogeneity in all results (P>0.10). For hip OA, three
      studies showed a WMD -0.21 (95%CI -0.82, 0.40). For knee OA, two studies showed
      WMD -0.95 (95%CI -2.64, 0.74). The summary WMD was -0.29 (95%CI -0.87, 0.28). Two
      long-term studies, one evaluating hip OA and another evaluating knee OA, analysed
      structural progression with radiographic measurements of joint space. In hip OA,
      there was statistical significant slowing of progression in contrast with knee OA
      that did not demonstrate this reduction. However, the overall effect was very
      different between studies (P=0.04 for hip OA and P= 0.85 for knee OA). The most
      frequent adverse event was diarrhea. 459 participants among 1083 participants
      that received diacerein (42%) were affected. 18% in the treatment group compared
      with 13% in the placebo group withdrew due to adverse events. AUTHORS'
      CONCLUSIONS: There is 'gold' level evidence that diacerein has a small,
      consistent benefit in improvement in pain. Further research is necessary to
      confirm the short and long-term effectiveness and toxicity of diacerein therapy
      in OA.

PMID- 16437520
TI  - Antenatal perineal massage for reducing perineal trauma.
AB  - BACKGROUND: Perineal trauma following vaginal birth can be associated with
      significant short- and long-term morbidity. Antenatal perineal massage has been
      proposed as one method of decreasing the incidence of perineal trauma.
      OBJECTIVES: To assess the effect of antenatal perineal massage on the incidence
      of perineal trauma at birth and subsequent morbidity. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 January
      2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library,
      Issue 1, 2005), PubMed (1966 to January 2005), EMBASE (1980 to January 2005) and
      reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials evaluating any described method of antenatal
      perineal massage undertaken for at least the last four weeks of pregnancy. DATA
      COLLECTION AND ANALYSIS: Both review authors independently applied the selection
      criteria, extracted data from the included studies and assessed study quality. We
      contacted study authors for additional information. MAIN RESULTS: Three trials
      (2434 women) comparing digital perineal massage with control were included. All
      were of good quality. Antenatal perineal massage was associated with an overall
      reduction in the incidence of trauma requiring suturing (three trials, 2417
      women, relative risk (RR) 0.91 (95% confidence interval (CI) 0.86 to 0.96),
      number needed to treat (NNT) 16 (10 to 39)). This reduction was statistically
      significant for women without previous vaginal birth only (three trials, 1925
      women, RR 0.90 (95% CI 0.84 to 0.96), NNT 14 (9 to 35)). Women who practised
      perineal massage were less likely to have an episiotomy (three trials, 2417
      women, RR 0.85 (95% CI 0.75 to 0.97), NNT 23 (13 to 111)). Again this reduction
      was statistically significant for women without previous vaginal birth only
      (three trials, 1925 women, RR 0.85 (95% CI 0.74 to 0.97), NNT 20 (11 to 110)). No
      differences were seen in the incidence of 1st or 2nd degree perineal tears or
      3rd/4th degree perineal trauma. Only women who have previously birthed vaginally
      reported a statistically significant reduction in the incidence of pain at three
      months postpartum (one trial, 376 women, RR 0.68 (95% CI 0.50 to 0.91) NNT 13 (7
      to 60)). No significant differences were observed in the incidence of
      instrumental deliveries, sexual satisfaction, or incontinence of urine, faeces or
      flatus for any women who practised perineal massage compared with those who did
      not massage. AUTHORS' CONCLUSIONS: Antenatal perineal massage reduces the
      likelihood of perineal trauma (mainly episiotomies) and the reporting of ongoing
      perineal pain and is generally well accepted by women. As such, women should be
      made aware of the likely benefit of perineal massage and provided with
      information on how to massage.

PMID- 16437521
TI  - Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus
      disease in solid organ transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and
      mortality in solid organ transplant recipients. Pre-emptive treatment with
      antiviral agents of patients with CMV viraemia has been widely adopted as an
      alternative to routine prophylaxis to prevent CMV disease. OBJECTIVES: This
      review was conducted to evaluate the efficacy of pre-emptive treatment in
      preventing symptomatic CMV disease. SEARCH STRATEGY: The Cochrane Central
      Register of Controlled Trials (CENTRAL, in The Cochrane Library Issue 2, 2005),
      MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005) and reference
      lists and conference proceedings were searched. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs) of pre-emptive treatment versus placebo, no
      treatment or antiviral prophylaxis in solid organ transplant recipients. DATA
      COLLECTION AND ANALYSIS: Two authors assessed the quality and extracted all data.
      Analysis was with a random-effects model and results expressed as relative risk
      (RR) and 95% confidence intervals (CI). MAIN RESULTS: Ten eligible trials (476
      patients) were identified, six of pre-emptive treatment versus placebo or
      treatment of CMV when disease occurred (standard care), three of pre-emptive
      treatment versus antiviral prophylaxis and one of oral versus intravenous pre
      emptive treatment. Compared with placebo or standard care, pre-emptive treatment
      significantly reduced the risk of CMV disease (six trials, 288 patients: RR 0.29,
      95% CI 0.11 to 0.80) but not acute rejection (three trials, 185 patient: RR 1.06,
      95% CI 0.64 to 1.76) or all-cause mortality (two trials, 176 patients: RR 1.23,
      95% CI 0.35 to 4.30). Comparative trials of pre-emptive therapy versus
      prophylaxis showed no significant difference in the risks of CMV disease, acute
      rejection or all-cause mortality. AUTHORS' CONCLUSIONS: Few RCTs have evaluated
      the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is
      effective compared with placebo or standard care, but additional head-to-head
      trials are required to determine the relative benefits and harms of pre-emptive
      therapy and prophylaxis to prevent CMV disease in solid organ transplant
      recipients.

PMID- 16437522
TI  - Antiangiogenic therapy with interferon alfa for neovascular age-related macular
      degeneration.
AB  - BACKGROUND: Antiangiogenic therapy is a new approach to the treatment of
      neovascular age-related macular degeneration. Interferon alfa is one
      antiangiogenic agent thought to function by inhibiting the migration and
      proliferation of vascular endothelial cells. It has been used in the treatment of
      hepatitis, solid tumors and hematologic malignancies. OBJECTIVES: The aim of this
      review was to investigate interferon alfa as a treatment modality for neovascular
      age-related macular degeneration. SEARCH STRATEGY: We searched and identified
      trials from the Cochrane Central Register of Controlled Trials (CENTRAL), which
      contains the Cochrane Eyes and Vision Group Trials Register, in The Cochrane
      Library (Issue 2, 2005), MEDLINE (1966 to 2005/06 week 1), EMBASE (1980 to
      2005/week 23), LILACS (Latin American and Caribbean Health Science Literature
      Database) (June 2005) and the reference lists of included studies. SELECTION
      CRITERIA: This review included randomized controlled trials evaluating interferon
      alfa therapy in people with neovascular age-related macular degeneration who were
      followed for at least one year. DATA COLLECTION AND ANALYSIS: Both review authors
      independently extracted data and assessed trial quality. No data synthesis was
      conducted as only one trial met the inclusion criteria. MAIN RESULTS: The one
      included trial enrolled and randomized 481 participants from 45 centers worldwide
      into four groups. The study allowed for analysis of the number of participants
      who had lost three or more lines of vision at 52 weeks in three interferon alfa
      2a groups versus placebo. The results show an odds ratio of 1.60 (95% Confidence
      Interval 1.01 to 2.53) indicating that interferon is associated with a 60%
      increased odds of losing three or more lines at 52 weeks. This finding is
      marginally statistical with a P value of 0.04 and indicates that the treatment
      has the potential for harm rather than benefit. AUTHORS' CONCLUSIONS: At present
      there is not enough evidence to recommend the use of interferon alfa-2a for the
      treatment of age-related macular degeneration.

PMID- 16437523
TI  - Auricular acupuncture for cocaine dependence.
AB  - BACKGROUND: Auricular acupuncture (insertion of acupuncture into a number,
      usually five, of specific points in the ear) is a widely-used treatment for
      cocaine dependence. OBJECTIVES: To determine whether auricular acupuncture is an
      effective treatment for cocaine dependence, and to investigate whether its
      effectiveness is influenced by the treatment regimen. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (The Cochrane Library
      Issue 3, 2004); MEDLINE (January 1966 to October 2004) , EMBASE (January 1988 to
      October 2004); PsycInfo (1985 to October 2004); CINAHL (1982 to October 2004);
      SIGLE (1980 to October 2004) and reference lists of articles. SELECTION CRITERIA:
      Randomised controlled trials comparing a therapeutic regimen of auricular
      acupuncture with sham acupuncture or no treatment for reduction of cocaine use in
      cocaine dependents. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted data from published reports and assessed study quality using the Drug
      and Alcohol CRG checklist. All authors were contacted for additional information;
      two provided data. Separate meta-analyses were conducted for studies comparing
      auricular acupuncture with sham acupuncture, and with no treatment. For the main
      cocaine use outcomes, analyses were conducted by intention to treat, assuming
      that missing data were treatment failures. Available case analyses, using only
      individuals who provided data, were also conducted. MAIN RESULTS: Seven studies
      with a total of 1,433 participants were included. All were of generally low
      methodological quality. No differences between acupuncture and sham acupuncture
      were found for attition RR 1.05 (95% CI 0.89 to 1.23) or acupuncture and no
      acupuncture: RR 1.06 (95% CI 0.90 to 1.26) neither for any measure of cocaine or
      other drug use. However, the number of participants included in meta-analyses was
      low, and power was limited. Moderate benefit or harm is not ruled out by these
      results. Methodological limitations of the included studies may have also made
      the results open to bias. AUTHORS' CONCLUSIONS: There is currently no evidence
      that auricular acupuncture is effective for the treatment of cocaine dependence.
      The evidence is not of high quality and is inconclusive. Further randomised
      trials of auricular acupuncture may be justified.

PMID- 16437524
TI  - Preimplantation genetic screening for abnormal number of chromosomes
      (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection.
AB  - BACKGROUND: In both in vitro fertilisation (IVF) and intracytoplasmic sperm
      injection (ICSI), selection of the most competent embryo(s) for transfer is
      generally based on morphological criteria. However, many women fail to achieve a
      pregnancy after transfer of good quality embryos. One of the presumed causes is
      that such morphologically normal embryos show an abnormal number of chromosomes
      (aneuploidies). In preimplantation genetic screening (PGS), embryos are analysed
      for aneuploidies and only embryos that are euploid for the chromosomes tested are
      transferred. This technique has been suggested and used to improve pregnancy
      rates for the following indications: (i) advanced maternal age, (ii) repeated IVF
      failure, (iii) repeated miscarriage and (iv) testicular sperm extraction (TESE)
      ICSI. Although PGS is used more and more often, its effectiveness is still
      unclear. OBJECTIVES: To assess the effectiveness of PGS in terms of live births
      in women undergoing IVF or ICSI treatment. SEARCH STRATEGY: We searched the
      Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2005),
      MEDLINE (1966 to present) and EMBASE (1980 to present) (searched March 2005) and
      reference lists of articles. We also contacted authors for providing additional
      data when necessary. SELECTION CRITERIA: Trials for all four suggested
      indications as mentioned above were sought. All relevant published randomised
      controlled trials were selected. They were eligible for inclusion if the
      comparison dealt with IVF/ICSI with PGS versus IVF/ICSI without PGS. DATA
      COLLECTION AND ANALYSIS: Relevant data were extracted independently by two
      authors. All trials were screened and analysed according to predetermined quality
      criteria. Validity was assessed in terms of method of randomisation, completeness
      of follow-up, intention-to-treat analysis and presence or absence of blinding.
      The primary outcome measure was live birth rate per woman. Secondary outcome
      measures were the proportion of women reaching embryo transfer, mean number of
      embryos transferred per transfer, clinical pregnancy rate, multiple pregnancy
      rate, miscarriage rate, ongoing pregnancy rate, proportion of women reaching
      embryo transfer after cryopreservation and proportion of women whose child has a
      congenital malformation. MAIN RESULTS: Two randomised controlled trials met our
      predetermined eligibility criteria. These trials used PGS for advanced maternal
      age. The primary outcome of live birth rate per woman was not significantly
      different in the PGS and control groups, though data were only available from one
      study. The live birth rate was 11% (21 out of 199) in the PGS group, versus 15%
      (29 out of 190) in the control group (OR 0.65; 95% CI 0.36 to 1.19). For a
      control group rate of 15%, these data suggest a live birth rate using PGS of
      between 4% and 17%. Ongoing pregnancy rate was provided in both studies. This was
      not significantly different with a combined odds ratio of 0.64 (95% CI 0.37 to
      1.09). For a control group rate of 20%, this suggests an ongoing pregnancy rate
      using PGS of between 8% and 21%. AUTHORS' CONCLUSIONS: To date there is
      insufficient data to determine whether PGS is an effective intervention in
      IVF/ICSI for improving live birth rates. Available data on PGS for advanced
      maternal age showed no difference in live birth rate and ongoing pregnancy rate.
      However, only two randomised trials were found, of which one included only 39
      patients. For both studies comments on their methodological quality can be made.
      Therefore more properly conducted randomised controlled trials are needed. Until
      such trials have been performed PGS should not be used in routine patient care.

PMID- 16437525
TI  - Planned early birth versus expectant management (waiting) for prelabour rupture
      of membranes at term (37 weeks or more).
AB  - BACKGROUND: Prelabour rupture of membranes at term is managed expectantly or by
      elective birth, but it is not clear if waiting for birth to occur spontaneously
      is better than intervening. OBJECTIVES: To assess the effects of planned early
      birth versus expectant management for women with term prelabour rupture of
      membranes on fetal, infant and maternal wellbeing. SEARCH STRATEGY: We searched
      the Cochrane Pregnancy and Childbirth Group Trials Register (November 2004), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,
      2004), MEDLINE (1966 to November 2004) and EMBASE (1974 to November 2004).
      SELECTION CRITERIA: Randomised or quasi-randomised trials of planned early birth
      compared with expectant management in women with prelabour rupture of membranes
      at 37 weeks' gestation or more. DATA COLLECTION AND ANALYSIS: Two review authors
      independently applied eligibility criteria, assessed trial quality and extracted
      data. A random-effects model was used. MAIN RESULTS: Twelve trials (total of 6814
      women) were included. Planned management was generally induction with oxytocin or
      prostaglandin, with one trial using homoeopathic caulophyllum. Overall, no
      differences were detected for mode of birth between planned and expectant groups:
      relative risk (RR) of caesarean section 0.94, 95% confidence interval (CI) 0.82
      to 1.08 (12 trials, 6814 women); RR of operative vaginal birth 0.98, 95% 0.84 to
      1.16 (7 trials, 5511 women). Significantly fewer women in the planned compared
      with expectant management groups had chorioamnionitis (RR 0.74, 95% CI 0.56 to
      0.97; 9 trials, 6611 women) or endometritis (RR 0.30, 95% CI 0.12 to 0.74; 4
      trials, 445 women). No difference was seen for neonatal infection (RR 0.83, 95%
      CI 0.61 to 1.12; 9 trials, 6406 infants). However, fewer infants under planned
      management went to neonatal intensive or special care compared with expectant
      management (RR 0.72, 95% CI 0.57 to 0.92, number needed to treat 20; 5 trials,
      5679 infants). In a single trial, significantly more women with planned
      management viewed their care more positively than those expectantly managed (RR
      of "nothing liked" 0.45, 95% CI 0.37 to 0.54; 5031 women). AUTHORS' CONCLUSIONS:
      Planned management (with methods such as oxytocin or prostaglandin) reduces the
      risk of some maternal infectious morbidity without increasing caesarean sections
      and operative vaginal births. Fewer infants went to neonatal intensive care under
      planned management although no differences were seen in neonatal infection rates.
      Since planned and expectant management may not be very different, women need to
      have appropriate information to make informed choices.

PMID- 16437526
TI  - Therapeutic communities for substance related disorder.
AB  - BACKGROUND: Therapeutic communities (TCs) are a popular treatment for the
      rehabilitation of drug users in the USA and Europe. OBJECTIVES: To determine the
      effectiveness of TC versus other treatments for substance dependents, and to
      investigate whether effectiveness is modified by client or treatment
      characteristics. SEARCH STRATEGY: We searched: Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 2, 2005); MEDLINE, EMBASE,
      Psycinfo, CINAHL, SIGLE from their inception to March 2004. Reference lists of
      studies were scanned. SELECTION CRITERIA: Randomised controlled trials comparing
      TC with other treatments, no treatment or another TC. DATA COLLECTION AND
      ANALYSIS: Two authors independently inspected abstracts, the methodological
      quality was assessed using Drug and Alcohol CRG checklist. When possible, data
      were summarised using relative risks and differences in means, otherwise results
      are presented as reported by authors. MAIN RESULTS: Seven studies were included.
      Differences between studies precluded any pooling of data, results are summarised
      for each trial individually: TC versus community residence: no significant
      differences for treatment completion; Residential versus day TC: attrition (first
      two weeks), and abstinence rates at six months significantly lower in the
      residential treatment group; Standard TC versus enhanced abbreviated TC: number
      of employed higher in standard TC RR 0.78 (95% CI 0.63, 0.96). Three months
      versus six months programme within modified TC, and six months versus 12 months
      programme within standard TC: completion rate higher in the three months
      programme and retention rate (40 days) significantly greater with the 12 months
      than 6 months programme. Two trials evaluated TCs within a prison setting: one
      reported significantly fewer re incarcerated 12 months after release from prison
      in the TC group compared with no treatment, RR 0.68 (95% CI 057, 0.81). In the
      other, people treated in prison with TC compared with Mental Health Treatment
      Programmes showed significantly fewer re incarcerations RR 0.28 (95% CI 0.13,
      0.63), criminal activity 0.69 (95% CI 0.52, 0.93) and alcohol and drug offences
      0.62 (95% CI 0.43, 0.90) 12 months after release from prison. AUTHORS'
      CONCLUSIONS: There is little evidence that TCs offer significant benefits in
      comparison with other residential treatment, or that one type of TC is better
      than another. Prison TC may be better than prison on it's own or Mental Health
      Treatment Programmes to prevent re-offending post-release for in-mates. However,
      methodological limitations of the studies may have introduced bias and firm
      conclusions cannot be drawn due to limitations of the existing evidence.

PMID- 16437527
TI  - Intraperitoneal chemotherapy for the initial management of primary epithelial
      ovarian cancer.
AB  - BACKGROUND: Ovarian cancer tends to be chemosensitive and confine itself to the
      surface of the peritoneal cavity for much of its natural history. These features
      have made it an obvious target for intraperitoneal chemotherapy. Chemotherapy for
      ovarian cancer is usually given as an intravenous infusion repeatedly over 5 to 8
      cycles. Intraperitoneal chemotherapy (IP) is given by infusion of the
      chemotherapeutic agent directly into the peritoneal cavity. This may increase the
      anticancer effect with fewer systemic adverse effects in comparison to
      intravenous therapy. OBJECTIVES: To determine if adding a component of the
      chemotherapy regime into the peritoneal cavity affects overall survival,
      progression free survival, quality of life (QOL) and toxicity for women receiving
      primary treatment of epithelial ovarian cancer. SEARCH STRATEGY: The reviewers
      searched the UK Cochrane trials register, Gynaecological Cancer Group Specialised
      Register, computer databases and handsearched and cascade searched the major
      gynaecological oncology journals. SELECTION CRITERIA: The analysis was restricted
      to randomised controlled trials assessing women with a new diagnosis of primary
      epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive
      surgery. Standard intravenous chemotherapy was compared with chemotherapy that
      included a component of intraperitoneal administration. DATA COLLECTION AND
      ANALYSIS: Two reviewers conducted data extraction independently. The reviewers
      retrieved data on overall and disease free survival as well as adverse events and
      QOL and then performed a meta-analysis of outcomes, using hazard ratios for time
      to-event variables and relative risks for dichotomous outcomes. MAIN RESULTS:
      Eight randomised trials studied 1819 women receiving primary treatment for
      ovarian cancer. Women were less likely to die if they received an intraperitoneal
      (IP) component to the chemotherapy (hazard ratio (HR) =0.79; 95% confidence
      interval (CI): 0.70 to 0.90)and the disease free interval (HR =0.79; 95%CI: 0.69
      to 0.90) was also significantly prolonged. There may be greater serious toxicity
      with regard to gastrointestinal effects, pain and fever but less ototoxicity with
      the intraperitoneal than the intravenous route. AUTHORS' CONCLUSIONS: This
      analysis establishes the benefit of IP chemotherapy. It increases overall
      survival and progression free survival from advanced ovarian cancer. The results
      of this meta-analysis provide the most reliable estimates of the relative
      survival benefits of IP over IV therapy and should be used as part of this
      decision making process. However, the potential for catheter related
      complications and toxicity needs to be considered when deciding on the most
      appropriate treatment for each individual woman. The optimal dose, timing and
      mechanism of administration cannot be addressed from this meta-analysis. This
      needs to be addressed in the next phase of clinical trials.

PMID- 16437528
TI  - Omega 3 fatty acid for the prevention of dementia.
AB  - BACKGROUND: Accruing evidence from observational and epidemiological studies
      suggests an inverse relationship between dietary intake of omega 3
      polyunsaturated fatty acid (PUFA) and risk of dementia. Postulated mechanisms
      that might qualify omega 3 PUFA as an interventional target for the primary
      prevention of dementia include its anti-atherogenic, anti-inflammatory, anti
      oxidant, anti-amyloid and neuroprotective properties. OBJECTIVES: To review the
      evidence that omega 3 PUFA supplementation prevents cognitive impairment and
      dementia in cognitively intact elderly persons. SEARCH STRATEGY: The Cochrane
      Dementia and Cognitive Improvement Group's (CDCIG) Specialized register, MEDLINE,
      EMBASE,CINAHL PsycINFO, AMED AND CENTRAL and several ongoing trials databases
      were searched on 5 and 6 October 2005. The CDCIG Register is updated regularly
      and contains records from all major medical databases and many ongoing trials
      databases. SELECTION CRITERIA: In order to be selected, trials needed to be
      randomized, placebo-controlled, doubled blinded, of minimum study duration of 6
      months, involved persons aged 60 years and above without pre-existing dementia at
      study onset, and employed cognitive endpoints. DATA COLLECTION AND ANALYSIS:
      Reviewers, working independently, were to select, quality assess and extract
      relevant data where appropriate and possible. In comparing intervention with
      placebo, the pooled odds ratios or weighted mean differences and standardized
      mean difference were to be estimated. MAIN RESULTS: There were no randomized
      trials found in the search that met the selection criteria. Results of two
      clinical trials are expected in 2008. AUTHORS' CONCLUSIONS: There is a growing
      body of evidence from biological, observational and epidemiological studies that
      suggests a protective effect of omega 3 PUFA against dementia. However, until
      data from randomized trials become available for analysis, there is no good
      evidence to support the use of dietary or supplemental omega 3 PUFA for the
      prevention of cognitive impairment or dementia.

PMID- 16437529
TI  - Clioquinol for the treatment of Alzheimer's Disease.
AB  - BACKGROUND: Alzheimer's disease (AD) may result in senile plaques being formed
      outside the brain as accumulation of beta-amyloid (Ass). OBJECTIVES: To evaluate
      the efficacy of clioquinol for the treatment of cognitive impairment due to
      Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive
      Improvement Group's Specialized Register was searched on 20 May 2005 using the
      terms clioquinol and PBT1. The Register contains records from major health care
      databases and many ongoing trial databases and is updated regularly. The Internet
      was searched using the term: clioquinol PBT1 Alzheimer*. SELECTION CRITERIA:
      Randomised double-blind trials in which treatment with clioquinol was
      administered to participants with Alzheimer's disease in parallel group
      comparison with placebo are included. DATA COLLECTION AND ANALYSIS: Two reviewers
      (RM, LJ) independently assessed the quality of trials according to the Cochrane
      Collaboration Handbook. The primary outcome measures of interest were cognitive
      function (as measured by psychometric tests) and global impression. The secondary
      outcome measures of interest were in the following areas: quality of life,
      functional performance, effect on carer, safety and adverse effects, and death.
      MAIN RESULTS: There was one included trial of clioquinol compared with placebo in
      36 patients. AUTHORS' CONCLUSIONS: It is not clear from the trial that clioquinol
      shows any positive clinical result on patients with AD. The two statistically
      significant positive results were seen for the more severely affected subgroup of
      patients. This effect was not maintained at the 36 week end-point. The sample
      size was small. Details of randomisation procedure or blinding were not reported.
      Further studies are needed to evaluate the potential for clioquinol as a
      treatment of AD. Trials of longer duration are also required, particularly
      because information about the side-effects of long-term use of clioquinol is
      limited.

PMID- 16437530
TI  - Pre-discharge "car seat challenge" for preventing morbidity and mortality in
      preterm infants.
AB  - BACKGROUND: Physiological monitoring studies indicate that some preterm infants
      experience episodes of oxygen desaturation, apnoea, or bradycardia when seated in
      standard car safety seats. The American Academy of Pediatrics recommends that all
      preterm infants should be assessed for cardiorespiratory stability in their car
      seat prior to discharge - the "car seat challenge". We aimed to assess the
      evidence to support this practice, specifically to determine whether the use of
      the car seat challenge prevents morbidity and mortality in preterm infants.
      OBJECTIVES: To assess the available evidence from randomised controlled trials
      that pre-discharge cardiorespiratory monitoring in a car safety seat prevents
      morbidity and mortality in preterm infants. SEARCH STRATEGY: We used the standard
      search strategy of the Cochrane Neonatal Review Group. This included searches of
      the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane
      Library, Issue 3, 2005), MEDLINE (1966 - September 2005), EMBASE (1980 -
      September 2005), CINAHL (1982 - September 2005), conference proceedings, and
      previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled
      trials that compared pre-discharge cardiorespiratory monitoring in a car seat
      versus no monitoring in preterm infants in the week prior to planned discharge
      from hospital. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane
      Neonatal Review Group, with separate evaluation of trial quality and data
      extraction by two review authors, and synthesis of data using relative risk, risk
      difference and weighted mean difference. MAIN RESULTS: We did not find any
      randomised controlled trials that fulfilled the eligibility criteria. AUTHORS'
      CONCLUSIONS: It is unclear whether undertaking a pre-discharge car seat challenge
      is beneficial or harmful to preterm infants. Further studies are needed to
      determine whether the car seat challenge accurately predicts the risk of
      clinically significant adverse events in preterm infants travelling in car seats.
      If this is shown to be the case then a large randomised controlled trial is
      needed to provide an unbiased assessment of its utility in pre-discharge
      assessment.

PMID- 16437531
TI  - Antipsychotic medication for elderly people with schizophrenia.
AB  - BACKGROUND: A large and growing number of older people across the world suffer
      from schizophrenia. Recommendations for their treatment are largely based on data
      extrapolated from studies of the use of antipsychotic medications in younger
      populations. In addition most manufacturers of such medications recommend
      prescription of reduced doses to the elderly. The evidence base for these
      assumptions is unclear and raises obvious questions regarding the appropriateness
      of such prescribing practice. OBJECTIVES: To find and assimilate good evidence of
      the effects of antipsychotic medication for treatment of schizophrenia in people
      over 65 years of age. SEARCH STRATEGY: We searched the Cochrane Schizophrenia
      Group's Register (May 2003). We inspected references of all included studies for
      further trials and contacted relevant pharmaceutical companies. SELECTION
      CRITERIA: All clinical randomised trials evaluating antipsychotic drugs for
      schizophrenia and schizophrenia-like psychoses in older people. DATA COLLECTION
      AND ANALYSIS: We extracted data independently. For homogenous dichotomous data,
      the random effects, relative risk (RR), and 95% confidence interval (CI) and,
      where appropriate, the numbers needed to treat (NNT) were calculated on an
      intention-to-treat basis. For continuous data, we calculated weighted mean
      differences (WMD). MAIN RESULTS: Two hundred and fifty two elderly people with
      schizophrenia participated in three relevant randomised controlled studies. We
      were unable to extract usable data on quality of life, satisfaction, service use,
      or economic outcomes. One small study (n=18) compared thioridazine with
      remoxipride (RR leaving the study early 1.0 CI 0.07 to 13.6). A second study
      (n=175) compared risperidone with olanzapine. Global state 'not improved/worse'
      was not significantly different between treatments (n= 171, RR 1.26 CI 0.8 to
      1.9); mental state PANSS total endpoint scores were also equivocal (n=171, RR
      0.98 CI 0.76 to 1.26) as were all cognitive function tests. The third study
      (subset n=59) compared olanzapine with haloperidol and mental state change scores
      (BPRS WMD -3.60 CI -10.8 to 3.6; PANSS WMD -6.00 CI -18.3 to 6.3) were equivocal.
      AUTHORS' CONCLUSIONS: Antipsychotics may be widely used in the treatment of
      elderly people with schizophrenia, however, based on this systematic review,
      there are little robust data available to guide the clinician with respect to the
      most appropriate drug to prescribe. Clearly reported large short, medium and long
      term randomised controlled trials with participants, interventions and primary
      outcomes that are familiar to those wishing to help elderly people with
      schizophrenia are long overdue.

PMID- 16437532
TI  - Cholinesterase inhibitors for Alzheimer's disease.
AB  - BACKGROUND: Since the introduction of the first cholinesterase inhibitor (ChEI)
      in 1997, most clinicians and probably most patients would consider the
      cholinergic drugs, donepezil, galantamine and rivastigmine, to be the first line
      pharmacotherapy for mild to moderate Alzheimer's disease.The drugs have slightly
      different pharmacological properties, but they all work by inhibiting the
      breakdown of acetylcholine, an important neurotransmitter associated with memory,
      by blocking the enzyme acetylcholinesterase. The most that these drugs could
      achieve is to modify the manifestations of Alzheimer's disease. Cochrane reviews
      of each ChEI for Alzheimer's disease have been completed (Birks 2005, Birks 2005b
      and Loy 2005). Despite the evidence from the clinical studies and the intervening
      clinical experience the debate on whether ChEIs are effective continues.
      OBJECTIVES: To assess the effects of donepezil, galantamine and rivastigmine in
      people with mild, moderate or severe dementia due to Alzheimer's disease. SEARCH
      STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized
      Register was searched using the terms 'donepezil', 'E2020' , 'Aricept' ,
      galanthamin* galantamin* reminyl, rivastigmine, exelon, "ENA 713" and ENA-713 on
      12 June 2005. This Register contains up-to-date records of all major health care
      databases and many ongoing trial databases. SELECTION CRITERIA: All unconfounded,
      blinded, randomized trials in which treatment with a ChEI was compared with
      placebo or another ChEI for patients with mild, moderate or severe dementia due
      to Alzheimer's disease. DATA COLLECTION AND ANALYSIS: Data were extracted by one
      reviewer (JSB), pooled where appropriate and possible, and the pooled treatment
      effects, or the risks and benefits of treatment estimated. MAIN RESULTS: The
      results of 13 randomized, double blind, placebo controlled trials demonstrate
      that treatment for periods of 6 months and one year, with donepezil, galantamine
      or rivastigmine at the recommended dose for people with mild, moderate or severe
      dementia due to Alzheimer's disease produced improvements in cognitive function,
      on average -2.7 points (95%CI -3.0 to -2.3), in the midrange of the 70 point ADAS
      Cog Scale. Study clinicians blind to other measures rated global clinical state
      more positively in treated patients. Benefits of treatment were also seen on
      measures of activities of daily living and behaviour. None of these treatment
      effects are large. There is nothing to suggest the effects are less for patients
      with severe dementia or mild dementia, although there is very little evidence for
      other than mild to moderate dementia.More patients leave ChEI treatment groups,
      approximately 29 %, on account of adverse events than leave the placebo groups
      (18%). There is evidence of more adverse events in total in the patients treated
      with a ChEI than with placebo. Although many types of adverse event were
      reported, nausea, vomiting, diarrhoea, were significantly more frequent in the
      ChEI groups than in placebo. There are four studies, all supported by one of the
      pharmaceutical companies, in which two ChEIs were compared, two studies of
      donepezil compared with galantamine, and two of donepezil compared with
      rivastigmine. In three studies the patients were not blinded to treatment, only
      the fourth, DON vs RIV/Bullock is double blind. Two of the studies provide little
      evidence, they are of 12 weeks duration, which is barely long enough to complete
      the drug titration. There is no evidence from DON vs GAL/Wilcock of a treatment
      difference between donepezil and galantamine at 52 weeks for cognition,
      activities of daily living, the numbers who leave the trial before the end of
      treatment, the number who suffer any adverse event, or any specific adverse
      event. There is no evidence from DON vs RIV/Bullock of a difference between
      donepezil and rivastigmine for cognitive function, activities of daily living and
      behavioural disturbance at two years. Fewer patients suffer adverse events on
      donepezil than rivastigmine. AUTHORS' CONCLUSIONS: The three cholinesterase
      inhibitors are efficacious for mild to moderate Alzheimer's disease. It is not
      possible to identify those who will respond to treatment prior to treatment.
      There is no evidence that treatment with a ChEI is not cost effective. Despite
      the slight variations in the mode of action of the three cholinesterase
      inhibitors there is no evidence of any differences between them with respect to
      efficacy. There appears to be less adverse effects associated with donepezil
      compared with rivastigmine. It may be that galantamine and rivastigmine match
      donepezil in tolerability if a careful and gradual titration routine over more
      than three months is used. Titration with donepezil is more straightforward and
      the lower dose may be worth consideration.

PMID- 16437533
TI  - Systemic antibiotics versus topical treatments for chronically discharging ears
      with underlying eardrum perforations.
AB  - BACKGROUND: Chronic suppurative otitis media (CSOM) causes ear discharge and
      impairs hearing. OBJECTIVES: To compare systemic antibiotics and topical
      antiseptics or antibiotics (excluding steroids) for treating chronically
      discharging ears with an underlying eardrum perforation (CSOM). SEARCH STRATEGY:
      The Cochrane ENT Disorders Group Specialised Register, Cochrane Central Register
      of Controlled Trials (CENTRAL, The Cochrane Library Issue 1, 2005), MEDLINE
      (January 1951 to March 2005), EMBASE (January 1974 to March 2005), LILACS
      (January 1982 to March 2005), AMED (1985 to March 2005), CINAHL (January 1982 to
      March 2005), OLDMEDLINE (January 1958 to December 1965) PREMEDLINE, Metadatabase
      of registers of ongoing trials (mRCT), and article references. SELECTION
      CRITERIA: Randomised controlled trials; any systemic versus topical treatment
      (excluding steroids); participants with CSOM. DATA COLLECTION AND ANALYSIS: One
      author assessed eligibility and quality, extracted data, entered data into
      RevMan; two authors provided a second assessment of titles and abstracts, and
      inputted where there was ambiguity. We contacted investigators for
      clarifications. MAIN RESULTS: Nine trials (833 randomised participants; 842
      analysed participants or ears). CSOM definitions and severity varied; some
      included mastoid cavity infections, other diagnoses, or complications.
      Methodological quality varied; generally poorly reported, follow-up short,
      handling of bilateral disease inconsistent. Topical quinolone antibiotics were
      better than systemic antibiotics at clearing discharge at 1-2 weeks: relative
      risks (RR) were, 3.21 (95% confidence interval (CI) 1.88 to 5.49) using systemic
      non-quinolone antibiotics (2 trials, N = 116), and 3.18 (1.87 to 5.43) using
      systemic quinolone (3 trials, N = 175); or 2.75 (1.38 to 5.46) in favour of
      systemic plus topical quinolone over systemic quinolone alone (2 trials, N = 90).
      No statistically significant benefit was seen at 2-4 weeks for topical non
      quinolone antibiotic (without steroids) or topical antiseptic over systemic
      antibiotics (mostly non-quinolones), but numbers were small: one trial tested
      topical non-quinolones (N = 31); two tested antiseptics (N = 152). No benefit of
      adding systemic to topical treatment at 1-2 weeks was detected either, although
      evidence was limited (three trials, N = 204). Evidence regarding safety was
      generally weak. Adverse events reported were generally mild, although hearing
      worsened by ototoxicity (damaging auditory hair cells) was seen with
      chloramphenicol drops (non-quinolone antibiotic). AUTHORS' CONCLUSIONS: Topical
      quinolone antibiotics can clear aural discharge better than systemic antibiotics;
      topical non-quinolone antibiotic (without steroids) or antiseptic results are
      less clear. Evidence regarding safety was weak. Further studies should clarify
      topical non-quinolones and antiseptic effectiveness, assess longer-term outcomes
      (for resolution, healing, hearing, or complications), and include further safety
      assessments, particularly to clarify the risks of ototoxicity and whether there
      may be fewer adverse events with topical quinolones than other topical or
      systemic treatments.

PMID- 16437534
TI  - Psychological therapies for people with borderline personality disorder.
AB  - BACKGROUND: Borderline personality disorder (BPD) is a relatively common
      personality disorder with a major impact on health services as those affected
      often present in crisis, often self-harming. OBJECTIVES: To evaluate the effects
      of psychological interventions for people with borderline personality disorder.
      SEARCH STRATEGY: We conducted a systematic search of 26 specialist and general
      bibliographic databases (December 2002) and searched relevant reference lists for
      further trials. SELECTION CRITERIA: All relevant clinical randomised controlled
      trials involving psychological treatments for people with BPD. The definition of
      psychological treatments included behavioural, cognitive-behavioural,
      psychodynamic and psychoanalytic. DATA COLLECTION AND ANALYSIS: We independently
      selected, quality assessed and data extracted studies. For binary outcomes we
      calculated a standard estimation of the risk ratio (RR), its 95% confidence
      interval (CI), and where possible the number need to help/harm (NNT/H). For
      continuous outcomes, endpoint data were preferred to change data. Non-skewed data
      from valid scales were summated using a weighted mean difference (WMD). MAIN
      RESULTS: We identified seven studies involving 262 people, and five separate
      comparisons. Comparing dialectical behaviour therapy (DBT) with treatment as
      usual studies found no difference for the outcome of still meeting SCID-II
      criteria for the diagnosis of BPD by six months (n=28, 1 RCT, RR 0.69 CI 0.35 to
      1.38) or admission to hospital in previous three months (n=28, 1 RCT, RR 0.77 CI
      0.28 to 2.14). Self harm or parasuicide may decrease at 6 to 12 months (n=63, 1
      RCT, RR 0.81 CI 0.66 to 0.98, NNT 12 CI 7 to 108). One study detected statistical
      difference in favour of people receiving DBT compared with those allocated to
      treatment as usual for average scores of suicidal ideation at 6 months (n=20, MD 
      15.30 CI -25.46 to -5.14). There was no difference for the outcome of leaving the
      study early (n=155, 3 RCTs, RR 0.74 CI 0.52 to 1.04). For the outcome of
      interviewer-assessed alcohol free days, skewed data are reported and tend to
      favour DBT. When a substance abuse focused DBT was compared with comprehensive
      validation therapy plus 12-step substance misuse programme no clear differences
      were found for service outcomes (n=23, 1 RCT, RR imprisoned 1.09 CI 0.64 to 1.87)
      or leaving the study early (n=23, 1 RCT, RR 7.58 CI 0.44 to 132.08). When
      dialectical behaviour therapy-oriented treatment is compared with client centred
      therapy no differences were found for service outcomes (n=24, 1 RCT, RR admitted
      0.33 CI 0.08 to 1.33). However, fewer people in the DBT group displayed
      indicators of parasuicidal behaviour (n=24, RR 0.13 CI 0.02 to 0.85, NNT 2 CI 2
      to 11). There were no differences for outcomes of anxiety and depression (n=24, 1
      RCT, RR anxiety BAI >/=10 0.60 CI 0.32 to 1.12; RR depression HDRS >/=10 0.43 CI
      0.14 to 1.28) but people who received DBT had less general psychiatric severity
      than those in the control (MD BPRS at 6 months -7.41 CI -13.72 to -1.10). Finally
      this one relevant study reports skewed data for suicidal ideation with
      considerably lower scores for people allocated to DBT. When psychoanalytically
      oriented partial hospitalization was compared with general psychiatric care the
      former tended to come off best. People who received treatment in a psychoanalytic
      orientated day hospital were less likely to be admitted into inpatient care when
      measured at different time points (e.g. n=44, RR admitted to inpatient 24 hour
      care >18 to 24 months 0.05 CI 0.00 to 0.77, NNT 3 CI 3 to 10) Fewer people in
      psychoanalytically oriented partial hospitalization needed day hospital
      intervention in the 18 months after discharge (n=44, 1 RCT, RR 0.04 CI 0.00 to
      0.59, NNT 2 CI 2 to 8). More people in the control group took psychotropic
      medication by the 30 to 36 month follow-up, than those receiving psychoanalytic
      treatment (n=44, 1 RCT, RR 0.44 CI 0.25 to 0.80, NNT 3 CI 2 to 7). Anxiety and
      depression scores were generally lower in the psychoanalytically oriented partial
      hospitalization group (n=44, 1 RCT, RR >/=14 on BDI 0.52 CI 0.34 to 0.80, NNT 3
      CI 3 to 6), as are global severity scores. People receiving psychoanalytic care
      in a day hospital had better social improvement in social adjustment using the
      SAS-SR at 6 to 12 months compared with people in general psychiatric care (MD 
      0.70 CI -1.08 to -0.32). Rates of attrition were the same (n=44, 1 RCT, RR
      leaving the study early 1.00 CI 0.23 to 4.42). AUTHORS' CONCLUSIONS: This review
      suggests that some of the problems frequently encountered by people with
      borderline personality disorder may be amenable to talking/behavioural treatments
      but all therapies remain experimental and the studies are too few and small to
      inspire full confidence in their results. These findings require replication in
      larger 'real-world' studies.

PMID- 16437535
TI  - Pharmacological interventions for people with borderline personality disorder.
AB  - BACKGROUND: Borderline Personality Disorder (BPD) is prevalent (2% in the general
      population, 20% among psychiatry in-patients) and has a major impact on health
      facilities as those affected often present in crisis but then make poor use of
      further attempts to help them. OBJECTIVES: To evaluate the effects of
      pharmacological interventions for people with borderline personality disorder.
      SEARCH STRATEGY: We conducted a systematic search of 26 specialist and general
      bibliographic databases (October 2002) and searched relevant reference lists for
      further trials. SELECTION CRITERIA: We included all randomised clinical trials
      comparing any psychoactive drugs with any other treatment for people with
      borderline personality disorder. DATA COLLECTION AND ANALYSIS: We independently
      selected, quality assessed and data extracted studies. For binary outcomes we
      calculated a standard estimation of the risk ratio (RR), its 95% confidence
      interval (CI), and where possible the number need to help/harm (NNT/H). For
      continuous outcomes, endpoint data were preferred to change data. Non-skewed data
      from valid scales were synthesised using a weighted mean difference (WMD). MAIN
      RESULTS: We found ten small (total n=554), short, randomised studies involving
      eight comparisons from which we could extract usable data. Studies comparing
      antidepressants with placebo were small (total n=79, 2 RCTs) but for ratings of
      anger fluoxetine may offer some improvement for those on antidepressant therapy
      over placebo (n=22, 1 RCT, RR anger not improved 0.30 CI 0.10 to 0.85, NNT 2 CI 2
      to 9). The one small study investigating the important outcome of attempted
      suicide found no difference between mianserin and placebo (n=38, 1 RCT, RR 0.82
      CI 0.44 to 1.54). Haloperidol may be better than antidepressants for symptoms of
      hostility and psychotism. There were few differences between MAOIs and placebo
      except that people given MAOIs were less hostile (n=62, 1 RCT, MD -9.19 CI -16.12
      to -2.26). Although some ratings were statistically significant the comparison of
      MAOIs with antipsychotics did not show convincing differences. Antipsychotics may
      effect some mental state symptoms more effectively than placebo but results are
      difficult to interpret clinically and there is little evidence of advantage of
      one antipsychotic over another. Finally mood stabilisers such as divalporex may
      help mental state (n=16, 1 RCT, RR no improvement in mental state 0.58 CI 0.36 to
      0.94, NNT 3 CI 2 to 17) but data are far from conclusive. AUTHORS' CONCLUSIONS:
      Pharmacological treatment of people with BPD is not based on good evidence from
      trials and it is arguable that future use of medication should be from within
      randomised trials. Current trials suggest that the positive effect of
      antidepressants, in particular, could be considerable. Well designed, conducted
      and reported clinically meaningful trials are possible and needed with, perhaps,
      the question of antidepressant versus placebo being addressed first.

PMID- 16437536
TI  - Pelvic floor muscle training versus no treatment, or inactive control treatments,
      for urinary incontinence in women.
AB  - BACKGROUND: Pelvic floor muscle training is the most commonly used physical
      therapy treatment for women with stress urinary incontinence. It is sometimes
      recommended for mixed and less commonly urge urinary incontinence. OBJECTIVES: To
      determine the effects of pelvic floor muscle training for women with urinary
      incontinence in comparison to no treatment, placebo or sham treatments, or other
      inactive control treatments. SEARCH STRATEGY: The Cochrane Incontinence Group
      Specialised Trials Register was searched. The date of the most recent search was
      1 December 2004. SELECTION CRITERIA: Randomised or quasi-randomised trials in
      women with stress, urge or mixed urinary incontinence (based on symptoms, signs,
      or urodynamics). One arm of the trial included pelvic floor muscle training
      (PFMT). Another arm was a no treatment, placebo, sham, or other inactive control
      treatment arm. DATA COLLECTION AND ANALYSIS: Trials were independently assessed
      for eligibility and methodological quality. Data were extracted then cross
      checked. Disagreements were resolved by discussion. Data were processed as
      described in the Cochrane Handbook (Higgins 2005). Trials were subgrouped by
      diagnosis. Formal meta-analysis was not undertaken because of study
      heterogeneity. MAIN RESULTS: Thirteen trials involving 714 women (375 PFMT, 339
      controls) met the inclusion criteria, but only six trials (403 women) contributed
      data to the analysis. Most studies were at moderate to high risk of bias, based
      on the trial reports. There was considerable variation in interventions used,
      study populations, and outcome measures. Women who did PFMT were more likely to
      report they were cured or improved than women who did not. PFMT women also
      experienced about one fewer incontinence episodes per day. There were too few
      data to draw conclusions about effects on other outcomes such as condition
      specific quality of life. Of the few adverse effects reported, none were serious.
      The trials in stress urinary incontinent women which suggested greater benefit
      recruited a younger population and recommended a longer training period than the
      one trial in women with detrusor overactivity (urge) incontinence. AUTHORS'
      CONCLUSIONS: Overall, the review provides some support for the widespread
      recommendation that PFMT be included in first-line conservative management
      programmes for women with stress, urge, or mixed, urinary incontinence.
      Statistical heterogeneity reflecting variation in incontinence type, training,
      and outcome measurement made interpretation difficult. The treatment effect might
      be greater in younger women (in their 40's and 50's) with stress urinary
      incontinence alone, who participate in a supervised PFMT programme for at least
      three months, but these and other uncertainties require testing in further
      trials.

PMID- 16437537
TI  - In heterozygous GDNF knockout mice the response of striatal dopaminergic system
      to acute morphine is altered.
AB  - Glial cell line-derived neurotrophic factor (GDNF) regulates striatal
      dopaminergic neurons. To study whether reduced endogenous GDNF affect morphine's
      effects on striatal dopamine transmission, we estimated extracellular
      concentrations of dopamine and its metabolites by microdialysis in vivo and
      tissue concentrations post mortem in mice lacking one GDNF allele (GDNF+/- mice).
      In the wild-type mice, acute morphine (5 and 10 mg/kg s.c.) increased accumbal
      dopamine output dose-dependently (maximally by 30 and 80%, respectively). In the
      GDNF+/- mice, 5 mg/kg of morphine enhanced the accumbal dopamine output maximally
      by 110%, and significantly more than morphine 10 mg/kg (maximally by 60%). Also,
      the response of extracellular accumbal DOPAC to acute morphine was significantly
      altered in the GDNF+/- mice. In mice of both genotypes, the responses to morphine
      in the caudate putamen were similar to but much less intense than those in the
      nucleus accumbens. Morphine at the doses 5, 10, and 30 mg/kg dose-dependently
      elevated the striatal tissue concentrations of DOPAC and HVA, but the effect of
      30 mg/kg was significantly smaller in the GDNF+/- mice than in their wild-type
      littermates. The binding of [(3)H]DAMGO to striatal membrane homogenates was
      similar between the genotypes. However, morphine induced antinociception in the
      GDNF+/- mice at a smaller dose than in the controls. The finding that reduced
      GDNF level alters the effects of morphine on striatal dopamine and our previous
      findings of elevated extracellular striatal dopamine concentrations and
      FosB/DeltaFosB expression in the GDNF+/- mice show the importance of GDNF in the
      regulation of striatal dopaminergic system.

PMID- 16437538
TI  - Postnatal expression of myostatin propeptide cDNA maintained high muscle growth
      and normal adipose tissue mass in transgenic mice fed a high-fat diet.
AB  - Myostatin plays a robust, negative role in controlling muscle mass. A disruption
      of myostatin function by transgenic expression of its propeptide (the 5'region,
      866 nucleotides) results in significant muscle growth (Yang et al., 2001. Mol Rep
      Dev 60:351-361). Studies from myostatin and the propeptide transgene mRNA
      indicated that myostatin mRNA was detected at day 10.5 postcoitum in fetal mice.
      Its level remained low, but increased by 180% during the postnatal fast-growth
      period (day 0-10). An early, high-level postnatal expression of the transgene was
      identified as being responsible for a highly muscled phenotype. High-fat diet
      induces adiposity in rodents. To study the effects of dietary fat on muscle
      growth and adipose tissue fat deposition in the transgenic mice, we challenged
      the mice with a high-fat diet (45% kcal fat) for 21 weeks. Transgenic mice showed
      24%-50% further enhancement of growth on the high-fat diet compared to the normal
      fat diet (P = 0.004) from 17 to 25 weeks of age. The total mass of the main
      muscles of transgenic mice showed a 27% increase on the high-fat diet compared to
      the normal-fat diet (P = 0.004), while the white adipose tissue mass of the
      transgenic mice was not significantly different from that of wild-type mice fed a
      normal-fat diet (P = 0.434). The high-fat diet induced wild-type mice developed
      190% greater mass of white adipose tissues compared to the normal-fat diet (P =
      0.008), which primarily resulted from enlarged adipocytes. These results
      demonstrate that disruption of myostatin function by its propeptide shifted
      dietary fat utilization toward muscle tissues with minimal effects on adiposity.
      These results suggest that enhancing muscle growth by myostatin propeptide or
      other means during the early developmental stage may serve as an effective means
      for obesity prevention.

PMID- 16437539
TI  - Fine-tuning of properties of bismacrocyclic dinuclear cyclidene receptors by N
      methylation.
AB  - N-Methylated bismacrocyclic Cu and Ni complexes were synthesised and structurally
      characterised in the solid state. Their properties in solution were analysed by
      using NMR and ESR spectroscopies and electrochemical methods. Face-to-face
      biscyclidenes linked through polymethylene chains form rectangular boxlike
      cations. These moieties can host some small guest molecules (water, pi-electron
      donating compounds) and are stabilised by a shell of neighbouring counterions.
      For the bismacrocyclic dinuclear complexes containing two nickel or two copper
      ions, the intramolecular interactions between the metallic centres are
      strengthened through methylation of the macrocyclic components, as compared with
      the nonmethylated species. We report the electron coupling created by two
      unpaired electrons coming from two copper centres observed by ESR spectroscopy.
      Methylation weakens the electron-acceptor properties of the complexes, which
      leads to less effective binding of the pi-electron-donating guests. It also
      increases the stability of the lower oxidation states. In the case of the copper
      complexes, both Cu(II)/Cu(I) and Cu(II)/Cu(III) reversible one-electron transfers
      are seen in the voltammograms. These changes in properties are interpreted as the
      consequences of steric repulsion between the methyl substituents and the
      macrocyclic ring.

PMID- 16437540
TI  - CNS viral infection diverts homing of antibody-secreting cells from lymphoid
      organs to the CNS.
AB  - Neurotropic coronavirus infection of mice results in acute encephalomyelitis
      followed by viral persistence. Whereas cellular immunity controls acute
      infection, humoral immunity regulates central nervous system (CNS) persistence.
      Maintenance of serum Ab was correlated with tissue distribution of virus-specific
      Ab-secreting cells (ASC). Although virus-specific ASC declined in cervical lymph
      node and spleen after infectious virus clearance, virus-specific serum Ab was
      sustained at steady levels, with a delay in neutralizing Ab. Virus-specific ASC
      within the CNS peaked rapidly 1 wk after control of infectious virus and were
      retained throughout chronic infection, consistent with intrathecal Ab synthesis.
      Surprisingly, frequencies of ASC in the BM remained low and only increased
      gradually. Nevertheless, virus-specific ASC induced by peripheral infection
      localized to both spleen and BM. The data suggest that CNS infection provides
      strong stimuli to recruit ASC into the inflamed tissue through sustained up
      regulation of the CXCR3 ligands CXCL9 and CXCL10. Irrespective of Ag deprivation,
      CNS retention of ASC coincided with elevated BAFF expression and ongoing
      differentiation of class II+ to class II-CD138+CD19+ plasmablasts. These results
      confirm the CNS as a major ASC-supporting environment, even after resolution of
      viral infection and in the absence of chronic ongoing inflammation.

PMID- 16437541
TI  - Role of prednisolone treatment in severe Mycoplasma pneumoniae pneumonia in
      children.
AB  - Mycoplasma pneumoniae pneumonia (MP) is responsible for 10-40% of cases of
      pediatric community-acquired pneumonia. Occasionally, progression to severe
      pneumonia occurs despite appropriate antibiotic therapy. We retrospectively
      evaluated the effect of prednisolone in 15 children with MP whose clinical and
      radiographic course worsened despite broad-spectrum antibiotics, including
      appropriate macrolides. The mean ( +/- SD) age was 6.1 +/- 1.9 years, and 10 were
      boys. All children had received macrolides at presentation, but they had
      persistent fever and progressively worsening radiographic findings. In addition
      to broad-spectrum antimicrobial therapy, we added prednisolone (1 mg/kg for 3-7
      days, then tapered over 7 days) on day 6 (+/-1.5 days) of admission. Fourteen
      children became afebrile within 24 hr, and their clinical status and radiographic
      findings improved over several days. The white blood cell count at presentation
      was 7,500 +/- 2,000/mm3, with a proportion demonstrating lymphopenia (lymphocyte
      differential, 19.7 +/- 5.7%). In conclusion, corticosteroid treatment appeared to
      be temporally associated with clinical and radiographic improvement, and may be
      helpful for reducing morbidity in children with macrolide-nonresponsive severe
      MP. Further studies may be warranted.

PMID- 16437542
TI  - Comment: analyses of models of ion actions under the combined action of AC and DC
      magnetic fields.
AB  - I show that the interaction of weak DC and ELF magnetic fields with contained
      ions cannot generate significant biological effects through changing the
      character of the ion orbits.

PMID- 16437544
TI  - The sensitivity of human event-related potentials and reaction time to mobile
      phone emitted electromagnetic fields.
AB  - There is some evidence to suggest that exposure to mobile phones (MPs) can affect
      neural activity, particularly in response to auditory stimuli. The current
      investigation (n = 120) aimed to test recent findings in this area, namely that
      N100 amplitude and latency would decrease, and that P300 latency and reaction
      time (RT) would increase under active relative to sham exposure during an
      auditory task. Visual measures were also explored. A double blind,
      counterbalanced, crossover design was employed where subjects attended two
      sessions 1 week apart. In both sessions participants (1) performed auditory and
      visual oddball tasks while electroencephalogram (EEG) was recorded with a MP set
      to sham exposure mounted over the temporal region, and (2) performed the same
      tasks while the handset was set to active/sham. When active, the MP transmitted
      for 30 min at 895 MHz (average power 250 mW, pulse modulated at 217 Hz, average
      SAR 0.11 W/kg). Paired t-tests compared difference scores from the sham/sham
      session to those from the sham/active condition. The study was designed to detect
      differences of 1?4 of a standard deviation with a power of 0.80. There was no
      significant difference between exposure conditions for any auditory or visual
      event related potential (ERP) component or RT. As previous positive findings were
      not replicated, it was concluded that there is currently no evidence that acute
      MP exposure affects these indices of brain activity.

PMID- 16437545
TI  - Effect of millimeter wave irradiation on tumor metastasis.
AB  - One of the major side effects of chemotherapy in cancer treatment is that it can
      enhance tumor metastasis due to suppression of natural killer (NK) cell activity.
      The present study was undertaken to examine whether millimeter electromagnetic
      waves (MMWs) irradiation (42.2 GHz) can inhibit tumor metastasis enhanced by
      cyclophosphamide (CPA), an anticancer drug. MMWs were produced with a Russian
      made YAV-1 generator. Peak SAR and incident power density were measured as 730 +/
      100 W/kg and 36.5 +/- 5 mW/cm(2), respectively. Tumor metastasis was evaluated
      in C57BL/6 mice, an experimental murine model commonly used for metastatic
      melanoma. The animals were divided into 5 groups, 10 animals per group. The first
      group was not given any treatment. The second group was irradiated on the nasal
      area with MMWs for 30 min. The third group served as a sham control for group 2.
      The fourth group was given CPA (150 mg/kg body weight, ip) before irradiation.
      The fifth group served as a sham control for group 4. On day 2, all animals were
      injected, through a tail vein, with B16F10 melanoma cells, a tumor cell line
      syngeneic to C57BL/6 mice. Tumor colonies in lungs were counted 2 weeks following
      inoculation. CPA caused a marked enhancement in tumor metastases (fivefold),
      which was significantly reduced when CPA-treated animals were irradiated with
      MMWs. Millimeter waves also increased NK cell activity suppressed by CPA,
      suggesting that a reduction in tumor metastasis by MMWs is mediated through
      activation of NK cells.

PMID- 16437546
TI  - Millimeter wave induced reversible externalization of phosphatidylserine
      molecules in cells exposed in vitro.
AB  - In vitro exposure of refrigerated samples (4 degrees C) of anti-coagulated blood
      with millimeter waves (MMWs) at incident power densities (IPDs) between 0.55 and
      1.23 W/cm2 has been found to induce clot formation. We found a small but
      statistically significant change in clot size with increasing IPD value. MMW
      exposure of blood samples starting at room temperature (22 degrees C) did not
      induce blood coagulation; neither did conventional heating at temperatures up to
      40 degrees C. Since cell-free plasma did not clot upon MMW exposure, the role of
      blood cells was particularly analyzed. Experiments on various mixtures of blood
      cells with plasma revealed an important role of red blood cells (RBC) in the
      coagulation process. Plasma coagulation also developed within the MMW beam above
      dense keratinocyte (HaCaT) monolayers suggesting it lacked cell-type specificity.
      We hypothesized that alteration of the membrane surface in exposed cells might be
      responsible for the circumscribed coagulation. The thrombogenic role of
      externalized phosphatidylserine (PS) molecules is well known. Therefore, we
      carried out experiments for immunolabeling PS molecules with fluorescein
      isothiocyanate (FITC)-conjugated Annexin V on exposed cells. Fluorescence
      microscopy of the adherent human keratinocytes (HaCaT) and murine melanoma cells
      (B16F10) showed that MMW exposure at an IPD of 1.23 W/cm2 is capable of inducing
      reversible externalization of PS molecules in cells within the beam area without
      detectable membrane damage. Nonadherent Jurkat cells exposed to MMW at an IPD of
      34.5 mW/cm2 also showed reversible PS externalization with flow cytometry,
      whether the cell temperature was held constant or permitted to rise. These
      results suggest that certain biological effects induced by MMWs could be
      initiated by membrane changes in exposed cells.

PMID- 16437547
TI  - Proliferation and apoptosis in a neuroblastoma cell line exposed to 900 MHz
      modulated radiofrequency field.
AB  - The aim of this study was to examine whether a modulated radiofrequency of the
      type used in cellular phone communications at a specific absorption rate (SAR)
      higher than International Commission on Non-ionizing Radiation Protection
      (ICNIRP) reference level for occupational exposure, could elicit alterations on
      proliferation, differentiation, and apoptosis processes in a neuroblastoma cell
      line. The cell line was exposed for 24, 48, and 72 h to 900 MHz radiofrequency
      and proliferation and differentiation were tested by WST-I assay and by a
      molecular analysis of specific markers, two oncogenes and a cytoskeleton protein,
      in exponential growth phase and in synchronized cell cultures. Apoptosis was
      evaluated by caspase activation analysis and by molecular detection of Poly (ADP
      ribose) polimerase (PARP) cleavage. Combined exposures to radiofrequency and to
      the differentiative agent retinoic acid or to the apoptotic inducer camptothecin
      were carried out to test possible interference between electromagnetic field and
      chemical agents. Overall our data suggest that 900 MHz radiofrequency exposure up
      to 72 h does not induce significant alterations in the three principal cell
      activities in a neuroblastoma cell line.

PMID- 16437548
TI  - The evolution of ATPase activity in SMC proteins.
AB  - The SMC (structural maintenance of chromosomes) proteins are a highly conserved
      and ubiquitous family of ATPases, found in nearly all living organisms examined,
      where they play crucial roles in transmission of the hereditary material.
      However, the extent to which efficient ATP hydrolysis is required for SMC
      function has been a matter of some debate. Here we investigate the potential
      functional significance of ATP binding and hydrolysis in different eukaryotic SMC
      proteins, both by comparing the conservation of conserved ATPase motifs and by
      exploring potential coevolution between associated domains. In this way, we have
      been able to account for the reduced requirement for ATPase activity in cohesin's
      SMC3 and demonstrate the greater apparent conservation requirements for such
      activity in condensin SMC proteins. Finally, we explore possible interactions
      between the SMC and non-SMC components of the condensin complex that are required
      for full condensin activity and may modulate ATPase activity in the holocomplex.

PMID- 16437549
TI  - Proposed structural models of the prothrombinase (FXa-FVa) complex.
AB  - Activated coagulation factor V (FVa) functions as a cofactor to factor Xa (FXa)
      in the conversion of prothrombin (PT) to thrombin. This essential procoagulant
      reaction, despite being the subject of extensive investigation, is not fully
      understood structurally and functionally. To elucidate the structure of the FXa
      FVa complex, we have performed protein:protein (Pr:Pr) docking simulation with
      the pseudo-Brownian Pr:Pr docking ICM package and with the shape-complementarity
      Pr:Pr docking program PPD. The docking runs were carried out using a new model of
      full-length human FVa and the X-ray structure of human FXa. Five representative
      models of the FXa-FVa complex were in overall agreement with some of the
      available experimental data, but only one model was found to be consistent with
      almost all of the reported experimental results. The use of hybrid docking
      approach (theoretical plus experimental) is definitively important to study such
      large macromolecular complexes. The FXa-FVa model we have created will be
      instrumental for further investigation of this macromolecular system and will
      guide future site directed mutagenesis experiments.

PMID- 16437550
TI  - Generation of stella-GFP transgenic mice: a novel tool to study germ cell
      development.
AB  - The relationship between germ cells and pluripotent embryonic stem (ES) cells is
      of particular interest, together with approaches to generate primordial germ cell
      (PGCs) from ES cells. A critical requirement in these experiments is the ability
      to unambiguously detect PGCs with the use of, for example, reporter genes. The
      currently available transgenic reporters do not show exclusive expression in PGCs
      at their earliest developmental stages. Here we describe the use of germline
      restricted expression of stella, which is currently the best marker gene for
      PGCs. We generated two stella-GFP reporters and show that both transgenes surpass
      other reporters in terms of timing and specificity of expression in PGCs.
      Additionally, we demonstrate the usefulness of stella-GFP during the derivation
      of PGCs from ES cells.

PMID- 16437552
TI  - Development of the blood-brain barrier: a historical point of view.
AB  - Although there has been considerable controversy since the observation by Ehrlich
      more than 100 years ago that the brain did not take up dyes from the vascular
      system, the concept of an endothelial blood-brain barrier (BBB) was confirmed by
      the unequivocal demonstration that the passage of molecules from blood to brain
      and vice versa was prevented by endothelial tight junctions (TJs). There are
      three major functions implicated in the term "BBB": protection of the brain from
      the blood milieu, selective transport, and metabolism or modification of blood-
      or brain-borne substances. The BBB phenotype develops under the influence of
      associated brain cells, especially astrocytic glia, and consists of complex TJs
      and a number of specific transport and enzyme systems that regulate molecular
      traffic across the endothelial cells. The development of the BBB is a complex
      process that leads to endothelial cells with unique permeability characteristics
      due to high electrical resistance and the expression of specific transporters and
      metabolic pathways. This review article summarizes the historical background
      underlying our current knowledge of the cellular and molecular mechanisms
      involved in the development and maintenance of the BBB.

PMID- 16437551
TI  - Sudden origins: a general mechanism of evolution based on stress protein
      concentration and rapid environmental change.
AB  - A major theme in Darwinian evolutionary theory is that novelty arises through a
      process in which organisms and their features are gradually transformed. Morgan
      provided Darwinism and the evolutionary synthesis with the idea that minor
      mutations produce the minuscule morphological variations on which natural
      selection then acts, and that, although mutation is random, once a process of
      gradual genetic modification begins, it becomes directional and leads to
      morphological, and consequently organismal, transformation. In contrast, studies
      on the role of cell membrane physical states in regulating the expression of
      stress proteins in response to environmental shifts indicate the existence of a
      downstream mechanism that prevents or corrects genetic change (i.e., maintains
      "DNA homeostasis"). However, episodic spikes in various kinds of environmental
      stress that exceed an organism's cells' thresholds for expression of proper
      amounts of stress proteins responsible for protein folding (including
      stochastically occurring DNA repair) may increase mutation rate and genetic
      change, which in turn will alter the pattern of gene expression during
      development. If severe stress disrupts DNA homeostasis during meiosis
      (gametogenesis), this could allow for the appearance of significant mutational
      events that would otherwise be corrected or suppressed. In evolutionary terms,
      extreme spikes in environmental stress make possible the emergence of new genetic
      and consequent developmental and epigenetic networks, and thus also the emergence
      of potentially new morphological traits, without invoking geographic or other
      isolating mechanisms.

PMID- 16437554
TI  - Broca's arrow: evolution, prediction, and language in the brain.
AB  - Brodmann's areas 44 and 45 in the human brain, also known as Broca's area, have
      long been associated with language functions, especially in the left hemisphere.
      However, the precise role Broca's area plays in human language has not been
      established with certainty. Broca's area has homologs in the great apes and in
      area F5 in monkeys, which suggests that its original function was not linguistic
      at all. In fact, great ape and hominid brains show very similar left-over-right
      asymmetries in Broca's area homologs as well as in other areas, such as homologs
      to Wernicke's area, that are normally associated with language in modern humans.
      Moreover, the so-called mirror neurons are located in Broca's area in great apes
      and area F5 in monkeys, which seem to provide a representation of cause and
      effect in a primate's environment, particularly its social environment. Humans
      appear to have these mirror neurons in Broca's area as well. Similarly, genetic
      evidence related to the FOXP2 gene implicates Broca's area in linguistic function
      and dysfunction, but the gene itself is a highly conserved developmental gene in
      vertebrates and is shared with only two or three differences between humans and
      great apes, five between humans and mice, and eight between humans and songbirds.
      Taking neurons and portions of the brain as discrete computational segments in
      the sense of constituting specific Turing machines, this evidence points to a
      predictive motor and conceptual function for Broca's area in primates, especially
      for social concepts. In human language, this is consistent with evidence from
      typological and cognitive linguistics.

PMID- 16437556
TI  - Effect of a mutation on the structure and dynamics of an alpha-helical antifreeze
      protein in water and ice.
AB  - One strategy of psychrophilic organisms to survive subzero temperature is to
      produce antifreeze protein (AFPs), which inhibit the growth of macromolecular
      ice. To better understand the binding mechanism, the structure and dynamics of
      several AFPs have been studied by nuclear magnetic resonance (NMR) and X-ray
      crystallography. The results have shown that different organisms can use diverse
      structures (alpha-helix, beta-helix, or different globular folds) to achieve the
      same function. A number of studies have focused on understanding the relationship
      between the alpha-helical structure of fish type I AFP and its function as an
      inhibitor of ice growth. The results have not explained whether the 90% activity
      loss caused by the conservative mutation of two threonines to serines
      (Thr13Ser/Thr24Ser) is attributable to a change in protein structure in solution
      or in ice. We examine here the structure and dynamics of the winter flounder type
      I AFP and the mutant Thr13Ser/Thr24Ser in both solution and solid states using a
      wide range of NMR approaches. Both proteins remain fully alpha-helical at all
      temperatures and in ice, demonstrating that the activity change must therefore
      not be attributable to changes in the protein fold or dynamics but differences in
      surface properties.

PMID- 16437555
TI  - Subcellular, cellular, and circuit mechanisms underlying classical conditioning
      in Hermissenda crassicornis.
AB  - A breakthrough for studying the neuronal basis of learning emerged when
      invertebrates with simple nervous systems, such as the sea slug Hermissenda
      crassicornis, were shown to exhibit classical conditioning. Hermissenda learns to
      associate light with turbulence: prior to learning, naive animals move toward
      light (phototaxis) and contract their foot in response to turbulence; after
      learning, conditioned animals delay phototaxis in response to light. The
      photoreceptors of the eye, which receive monosynaptic inputs from statocyst hair
      cells, are both sensory neurons and the first site of sensory convergence. The
      memory of light associated with turbulence is stored as changes in intrinsic and
      synaptic currents in these photoreceptors. The subcellular mechanisms producing
      these changes include activation of protein kinase C and MAP kinase, which act as
      coincidence detectors because they are activated by convergent signaling
      pathways. Pathways of interneurons and motorneurons, where additional changes in
      excitability and synaptic connections are found, contribute to delayed
      phototaxis. Bursting activity recorded at several points suggest the existence of
      small networks that produce complex spatiotemporal firing patterns. Thus, the
      change in behavior may be produced by a nonlinear transformation of
      spatiotemporal firing patterns caused by plasticity of synaptic and intrinsic
      channels. The change in currents and the activation of PKC and MAPK produced by
      associative learning are similar to those observed in hippocampal and cerebellar
      neurons after rabbit classical conditioning, suggesting that these represent
      general mechanisms of memory storage. Thus, the knowledge gained from further
      study of Hermissenda will continue to illuminate mechanisms of mammalian
      learning.

PMID- 16437557
TI  - Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2.
AB  - OBJECTIVE: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to
      optic atrophy has been designated as hereditary motor and sensory neuropathy type
      VI (HMSN VI). Reports of affected families have indicated autosomal dominant and
      recessive forms, but the genetic cause of this disease has remained elusive.
      METHODS: Here, we describe six HMSN VI families with a subacute onset of optic
      atrophy and subsequent slow recovery of visual acuity in 60% of the patients.
      Detailed clinical and genetic studies were performed. RESULTS: In each pedigree,
      we identified a unique mutation in the gene mitofusin 2 (MFN2). In three
      families, the MFN2 mutation occurred de novo; in two families the mutation was
      subsequently transmitted from father to son indicating autosomal dominant
      inheritance. INTERPRETATION: MFN2 is a mitochondrial membrane protein that was
      recently reported to cause axonal CMT type 2A. It is intriguing that MFN2 shows
      functional overlap with optic atrophy 1 (OPA1), the protein underlying the most
      common form of autosomal dominant optic atrophy, and mitochondrial encoded
      oxidative phosphorylation components as seen in Leber's hereditary optic atrophy.
      We conclude that autosomal dominant HMSN VI is caused by mutations in MFN2,
      emphasizing the important role of mitochondrial function for both optic atrophies
      and peripheral neuropathies.

PMID- 16437558
TI  - Defining the response to interferon-beta in relapsing-remitting multiple
      sclerosis patients.
AB  - OBJECTIVE: Many patients with multiple sclerosis (MS) are currently receiving
      treatment with interferon (IFN)-beta. Early identification of nonresponder
      patients is crucial to try different therapeutic approaches. We investigated
      various criteria of treatment response to assess which criterion better
      identifies patients with a poor response. METHODS: We studied relapsing-remitting
      MS (RRMS) patients treated with IFN-beta and followed them up for at least 2
      years. Expanded Disability Status Score was scored every 3 months and relapses
      were recorded. We analyzed various criteria based on relapses, disability
      progression, or both. RESULTS: Three hundred ninety-three patients were included.
      After 2 years of treatment, we observed a proportion of nonresponders, ranging
      from 7 to 49% depending on the stringency of the criteria used. Criteria based in
      disability progression had higher sensitivity, specificity, and accuracy. The
      hazard ratio for the development of marked disability after 6 years of treatment
      was 39.6 (95% confidence interval, 16.6-94.4) among the patients who fulfilled
      the criterion based only in disability progression. INTERPRETATION: Criteria of
      response to IFN-beta therapy in RRMS using disability progression are more
      clinically relevant than those based only in relapse rate. This finding may be
      important for the counseling and care of RRMS patients treated with IFN-beta.

PMID- 16437559
TI  - Lrrk2 and Lewy body disease.
AB  - OBJECTIVE: The Lrrk2 kinase domain G2019S substitution is the most common genetic
      basis of familial and sporadic parkinsonism. Patients harboring the G2019S
      substitution usually present with clinical Parkinson's disease. METHODS: Herein,
      we report that the most common neuropathology of G2019S-associated Parkinson's
      disease is Lewy body disease. RESULTS: Lrrk2 G2019S was observed in approximately
      2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The
      mutation was also found in one control subject and one Alzheimer's disease
      patient, reflecting reduced penetrance. INTERPRETATION: Therapeutic strategies
      targeted at modulating Lrrk2 kinase activity may be important to treat patients
      with genetically defined familial or typical sporadic Parkinson's disease.

PMID- 16437560
TI  - T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy.
AB  - OBJECTIVE: To determine the clinical consequences of the PMP22 point mutation,
      T118M, which has been previously considered to either cause an autosomal
      recessive form of Charcot-Marie-Tooth (CMT) disease or be a benign polymorphism.
      METHODS: We analyzed patients from five separate kindreds and characterized their
      peripheral nerve function by clinical and electrophysiological methods. RESULTS:
      All heterozygous patients had clinical and/or electrophysiological features of a
      neuropathy similar to hereditary neuropathy with liability to pressure palsies
      (HNPPs). The homozygous patient had a severe axonal neuropathy without features
      of demyelination. INTERPRETATION: These findings suggest that T118M PMP22 retains
      some normal PMP22 activity, allowing the formation of compact myelin and normal
      nerve conduction velocities in the homozygous state. Taken together, these
      findings suggest that T118M is a pathogenic mutation causing a dominantly
      inherited form of CMT by a partial loss of PMP22 function.

PMID- 16437561
TI  - Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis.
AB  - OBJECTIVE: Our objective was to investigate a role of the intracellular tyrosine
      phosphatase PTPN22*R620W variant in autoimmune myasthenia gravis (MG),
      considering disease heterogeneity. METHODS: We used a case-control design,
      comparing 470 patients and 296 controls, all French whites. Patients were
      categorized depending on the presence of a thymoma and serum anti-titin
      antibodies. RESULTS: The 620W risk allele was increased in 293 nonthymoma
      patients without anti-titin antibodies (odds ratio, 1.97; 95% confidence
      interval, 1.32-2.97, p = 0.00059) but not in nonthymoma patients with anti-titin
      antibodies or in thymoma patients. INTERPRETATION: Our genetic findings
      strengthen the concept that these groups of patients correspond to etiologically
      distinct disease entities.

PMID- 16437562
TI  - The dominant form of vanishing white matter-like leukoencephalopathy represents
      autosomal dominant leukodystrophy.

PMID- 16437564
TI  - Can we identify a CT-based tissue window for thrombolysis without CTP?

PMID- 16437565
TI  - Periodic electroencephalogram complexes in a patient with variant Creutzfeldt
      Jakob disease.
AB  - OBJECTIVE: Based on the current criteria, the diagnosis of "possible" or
      "probable" variant Creutzfeldt-Jakob disease (vCJD) implies the absence of
      periodic sharp wave complexes (PSWCs) in the electroencephalogram (EEG). To
      verify this point, we investigated the development of the EEG changes along the
      course of the disease in a pateint with vCJD. METHODS: Long-lasting EEG
      polygraphic recordings were performed once a month during the last year of
      illness. RESULTS: We found the occurrence of a typical EEG periodic pattern in
      the late clinical stage of the vCJD patient. INTERPRETATION: In the light of our
      finding, the diagnostic criteria for vCJD should be amended to include the
      possibility of a typical periodic EEG in advanced stages of disease in cases with
      long survival.

PMID- 16437566
TI  - Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine monkeys.
AB  - OBJECTIVE: The objective of the present study was to investigate the effect of
      docosahexaenoic acid (DHA), a polyunsaturated fatty acid (omega-3), on levodopa
      induced dyskinesias (LIDs) in parkinsonian 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-treated monkeys. METHODS: We explored the effect of DHA
      in two paradigms. First, a group of MPTP monkeys was primed with levodopa for
      several months before introducing DHA. A second group of MPTP monkeys (de novo)
      was exposed to DHA before levodopa therapy. RESULTS: DHA administration reduced
      LIDs in both paradigms without alteration of the anti-parkinsonian effect of
      levodopa indicating that DHA can reduce the severity or delay the development of
      LIDs in a nonhuman primate model of Parkinson's disease. INTERPRETATION: These
      results suggest that DHA can reduce the severity or delay the development of LIDs
      in a nonhuman primate model of Parkinson's disease. DHA may represent a new
      approach to improve the quality of life of Parkinson's disease patients.

PMID- 16437567
TI  - Length dependence in polyneuropathy associated with IgM gammopathy.
AB  - OBJECTIVE: In polyneuropathy associated with monoclonal IgM gammopathy, nerve
      conduction studies may show disproportionate distal slowing consistent with
      segmental demyelination. This was suggested to represent a length-dependent
      demyelinating process, starting in distal and proceeding to proximal segments.
      Because the evidence for this is incomplete, we assessed whether length
      dependence occurs in IgM neuropathy. METHODS: In 22 patients with IgM neuropathy,
      20 disease controls with chronic inflammatory demyelinating polyneuropathy (CIDP)
      and 36 normal controls, we investigated motor conduction, sensory conduction, and
      needle electromyography for nerves with short, intermediate-length, and long
      axons as well as conduction in short segments of the ulnar nerve from proximal to
      distal. To compare variables in nerves of different length, we normalized
      individual values with respect to the median in normal controls. RESULTS: In IgM
      neuropathy, distal slowing and features of axon loss increased with nerve length,
      and ulnar nerve conduction became gradually slower from proximal to distal when
      the elbow segment was excluded. In CIDP, no clear length dependence was found
      except for distal amplitude. INTERPRETATION: The disproportionate distal slowing
      in IgM neuropathy may be part of a length-dependent process, assuming that this
      process is randomly distributed due to a generalized exposure to IgM.

PMID- 16437568
TI  - Reply: To PMID 16374827.

PMID- 16437569
TI  - Ictal hemodynamic changes in late-onset rasmussen encephalitis.

PMID- 16437570
TI  - Multiple mapping method: a novel approach to the sequence-to-structure alignment
      problem in comparative protein structure modeling.
AB  - A major bottleneck in comparative protein structure modeling is the quality of
      input alignment between the target sequence and the template structure. A number
      of alignment methods are available, but none of these techniques produce
      consistently good solutions for all cases. Alignments produced by alternative
      methods may be superior in certain segments but inferior in others when compared
      to each other; therefore, an accurate solution often requires an optimal
      combination of them. To address this problem, we have developed a new approach,
      Multiple Mapping Method (MMM). The algorithm first identifies the alternatively
      aligned regions from a set of input alignments. These alternatively aligned
      segments are scored using a composite scoring function, which determines their
      fitness within the structural environment of the template. The best scoring
      regions from a set of alternative segments are combined with the core part of the
      alignments to produce the final MMM alignment. The algorithm was tested on a
      dataset of 1400 protein pairs using 11 combinations of two to four alignment
      methods. In all cases MMM showed statistically significant improvement by
      reducing alignment errors in the range of 3 to 17%. MMM also compared favorably
      over two alignment meta-servers. The algorithm is computationally efficient;
      therefore, it is a suitable tool for genome scale modeling studies.

PMID- 16437571
TI  - Skin sympathetic adrenergic innervation: an immunofluorescence confocal study.
AB  - OBJECTIVE: The aim of this study was to characterize sympathetic adrenergic
      innervation of the skin in healthy subjects using dopamine beta hydroxylase
      (DbetaH) as a specific marker for noradrenergic fibers. METHODS: Sympathetic
      adrenergic innervation of human skin was studied in 10 healthy subjects by
      indirect immunofluorescence and confocal microscopy applied to punch skin
      biopsies. Noradrenergic fibers were identified both in glabrous and hairy skin
      using DbetaH antibody. RESULTS: DbetaH immunoreactive fibers were mainly
      localized in arteriovenous anastomoses, arrector pilorum muscles, and arterioles,
      whereas few adrenergic fibers were found around sweat glands. INTERPRETATION: Our
      description of sympathetic adrenergic innervation of human skin aims to improve
      the diagnostic ability of skin biopsy to detect selective autonomic nervous
      system disorders.

PMID- 16437573
TI  - Neurological impact of vasopressin dysregulation and hyponatremia.
AB  - Hyponatremia is frequently associated with neurological disease, neurosurgical
      procedures, and use of psychoactive drugs. Arginine vasopressin (AVP), or
      antidiuretic hormone, is the principal physiological regulator of water and
      electrolyte balance, and disruption of the normal AVP response to osmotic stimuli
      is a common cause of dilutional hyponatremia in neurological disorders. The
      hyponatremia-induced shift in water from the extracellular to the intracellular
      compartment can lead to cerebral edema and serious neurological complications,
      especially if the decrease in serum sodium concentration ([Na+]) is large or
      rapid. Overly rapid correction of the serum [Na+] may lead to osmotic
      demyelination and irreversible brain injury. Fluid restriction is considered
      first-line treatment and pharmacological agents currently used in the treatment
      of hyponatremia are limited by inconsistent response and adverse side effects.
      AVP receptor antagonists represent a new approach to the treatment of
      hyponatremia by blocking tubular reabsorption of water by binding to V2 receptors
      in the renal collecting ducts, resulting in aquaresis. Initial clinical
      experience with AVP receptor antagonists for hyponatremia has shown that these
      agents augment free water clearance, decrease urine osmolality, and correct serum
      [Na+] and serum osmolality. Controlled clinical trials now underway will help
      elucidate the role of AVP receptor antagonism in the treatment of hyponatremia.

PMID- 16437572
TI  - Mild-onset presentation of Canavan's disease associated with novel G212A point
      mutation in aspartoacylase gene.
AB  - We describe two sisters with a mild-onset variant of Canavan's disease who
      presented at age 50 and 19 months with developmental delay but without
      macrocephaly, hypotonia, spasticity, or seizures. Remarkably, both patients had
      age-appropriate head control, gross motor development, and muscle tone. There
      were very mild deficits in fine motor skills, coordination, and gait. Both
      sisters had a history of strabismus, but otherwise vision was normal. The older
      child showed evidence of mild cognitive and social impairment, whereas language
      and behavior were normal for age in the infant. Both patients were found to be
      compound heterozygotes for C914A (A305E) and G212A (R71H) mutations in ASPA. Like
      all other known ASPA mutations, this previously unknown G212A mutation appears to
      have low absolute enzyme activity. Nevertheless, it is associated in these
      patients with an extremely benign phenotype that is highly atypical of Canavan's
      disease. Biochemical and clinical data were evaluated using a generalized linear
      mixed model generated from 25 other subjects with Canavan's disease. There were
      statistically significant differences in brain chemistry and clinical
      evaluations, supporting a distinct variant of Canavan's disease. Future studies
      of ASPA enzyme structure and gene regulation in these subjects could lead to a
      better understanding of Canavan's pathophysiology and improvements in ASPA gene
      therapy.

PMID- 16437574
TI  - Genotypic and phenotypic spectrum of PANK2 mutations in patients with
      neurodegeneration with brain iron accumulation.
AB  - OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) is a group of
      disorders characterized by magnetic resonance imaging (MRI) changes in basal
      ganglia. Both missense and nonsense mutations have been found in such patients in
      a gene encoding the mitochondrial pantothenate kinase (PANK2). METHODS: We
      completed a mutation screen in 72 patients with the diagnosis NBIA based on
      clinical findings and radiological imaging. The entire coding region of the PANK2
      gene (20p12.3) was investigated for point mutations and deletions. RESULTS: We
      uncovered both mutant alleles in 48 patients. Deletions accounted for 4% of
      mutated alleles. Patients with two loss-of-function alleles (n = 11) displayed
      symptoms always at an early stage of life. In the presence of missense mutations
      (n = 37), the age of onset correlated with residual activity of the pantothenate
      kinase. Progression of disease measured by loss of ambulation was variable in
      both groups. We did not observe a strict correlation between the eye-of-the-tiger
      sign and PANK2 mutations. In 24 patients, no PANK2 mutation was identified.
      INTERPRETATION: Deletion screening of PANK2 should be part of the diagnostic
      spectrum. Factors other than enzymatic residual activity are determining the
      course of disease. There are strong arguments in favor of locus heterogeneity.

PMID- 16437576
TI  - Optimizing an evidence-based causative classification system for ischemic stroke.

PMID- 16437575
TI  - The human immunodeficiency virus reduces network capacity: acoustic noise effect.
AB  - OBJECTIVE: Increased acoustic noise (AN) during working memory leads to increased
      brain activation in healthy individuals and may have greater impact in human
      immunodeficiency virus (HIV) patients. RESULTS: Compared with control subjects,
      HIV patients showed reduced AN activation and lower neuronal marker N
      acetylaspartate in prefrontal and parietal cortices. Competing use of the working
      memory network between AN and cognitive load showed lower dynamic range of the
      hemodynamic responses in prefrontal and parietal cortices in HIV patients.
      INTERPRETATION: These findings suggest that reduced reserve capacity of the
      working memory network in HIV patients and additional stress (eg, AN) might
      exhaust the impaired network for more demanding tasks.

PMID- 16437577
TI  - Apoe epsilon2-epsilon4 genotype is a possible risk factor for primary progressive
      aphasia.

PMID- 16437578
TI  - Increased midbrain gray matter in Tourette's syndrome.
AB  - OBJECTIVE: To investigate cerebral structure in Tourette's syndrome (TS).
      METHODS: Voxel-based morphometry study of high-resolution MRIs in 31 TS patients
      compared with 31 controls. RESULTS: Increased gray matter mainly in the left
      mesencephalon in 31 TS patients. INTERPRETATION: This result constitutes strong
      and direct evidence supporting Devinsky's hypothesis (Devinsky O. Neuroanatomy of
      Gilles de la Tourette's syndrome. Possible midbrain involvement. Arch Neurol
      1983;40:508-514) according to which midbrain disturbances play an important
      pathogenic role in TS.

PMID- 16437579
TI  - Low stability of Huntington muscle mitochondria against Ca2+ in R6/2 mice.
AB  - OBJECTIVE: The aim of the present work was the detection of Mitochondrial
      dysfunction of Huntington's disease (HD). METHODS: We investigated muscle and
      muscle mitochondria of 14- to 16-week-old R6/2 mice in comparison with wild-type
      mice. RESULTS: Atrophic fibers, increased fuchsinophilic aggregates, and reduced
      cytochrome c oxidase (15%) were found in HD muscle. With swelling measurements
      and Ca2+ accumulation experiments, a decreased stability of HD mitochondria
      against Ca2+-induced permeability transition was detected. Complex I-dependent
      respiration of HD mitochondria was more sensitive to inhibition by adding 10
      microm Ca2+ than wild-type mitochondria. INTERPRETATION: Data suggest that the
      decreased stability of HD mitochondria against Ca2+ contributes to energetic
      depression and cell atrophy.

PMID- 16437580
TI  - Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy.
AB  - OBJECTIVE: We examined the sarcolemma of skeletal muscle from patients with
      facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine
      and human muscular dystrophies, its organization and relationship to nearby
      contractile structures are altered. METHODS: Unfixed biopsies of control and FSHD
      deltoid and biceps muscles, snap-frozen at resting length, were cryosectioned,
      indirectly immunolabeled with fluorescent antibodies to sarcolemmal and
      myofibrillar markers, and examined with confocal microscopy to localize the
      immunolabeled proteins. Glutaraldehyde-fixed samples were stained with heavy
      metals, embedded, thin-sectioned, and examined with electron microscopy to
      determine the relationship between the sarcolemma and the underlying myofibrils.
      RESULTS: Confocal microscopy showed that some of the structures at the sarcolemma
      in FSHD samples were misaligned with respect to the underlying contractile
      apparatus. Electron microscopy showed a significant increase in the distance
      between the sarcolemma and the nearest myofibrils, from less than 100 nm in
      controls to values as high as 550 nm in FSHD. INTERPRETATION: Our results show
      that the pathophysiology of FSHD includes novel changes in the organization of
      the sarcolemma and its association with nearby contractile structures and suggest
      that, as in other muscular dystrophies, the integrity of the sarcolemma may be
      compromised in FSHD.

PMID- 16437581
TI  - Cleavage of cystatin C in the cerebrospinal fluid of patients with multiple
      sclerosis.
AB  - OBJECTIVE: The diagnosis of multiple sclerosis (MS) can be challenging because of
      the lack of a specific diagnostic test. Recent advances in proteomics, however,
      offer new opportunities for biomarker discovery and the study of disease
      pathogenesis. METHODS: We analyzed cerebrospinal fluid (CSF) samples from 29
      patients with MS or clinically isolated syndromes (CIS), 27 patients with
      transverse myelitis (TM), 50 patients with human immunodeficiency virus (HIV)
      infection, and 27 patients with other neurological diseases (ONDs) by surface
      enhanced laser desorption/ionization time-of-flight mass spectroscopy. RESULTS:
      We found a unique protein of 12.5 kDa that was 100% specific for MS/CIS compared
      with TM or OND. Low levels of this protein were found in some patients with HIV
      infection. Tandem mass spectroscopy of a tryptic digest of this 12.5 kDa protein
      identified it as a cleavage product of full-length cystatin C (13.4 kDa), an
      important inhibitor of cysteine proteases including the cathepsins. Although
      total cystatin C levels in the MS patients was not different compared with
      controls, the patients with the highest 12.5/13.4 peak ratios also had the
      greatest cathepsin B inhibitory activity. INTERPRETATION: This suggests that
      cleavage of cystatin C may be an adaptive host response and may identify a
      subgroup of patients with MS.

PMID- 16437582
TI  - Functional role of the basal ganglia in the planning and execution of actions.
AB  - OBJECTIVE: Recent studies of functional brain imaging have shown the involvement
      of the basal ganglia in executive processes such as planning and set-shifting.
      However, the specific contributions of the striatum in those processes remain
      unknown. This study aimed to test the hypothesis that the caudate nucleus is
      primarily involved in the preparation of a novel action and not in set-shifting
      per se. METHODS: In the present event-related functional magnetic resonance
      imaging (fMRI) study, a new task was developed that permitted, for the first
      time, to distinguish between shifts in classification when the rule is implicitly
      given by the task from shifts that require cognitive comparison and planning.
      RESULTS: Significantly increased activity in the caudate nucleus and the putamen
      was observed only in conditions in which cognitive planning was required to
      perform a set-shift, whereas significant activation was seen in the subthalamic
      nucleus (another region of the basal ganglia) in all shifting conditions whether
      or not planning was required. INTERPRETATION: We suggest that the caudate nucleus
      and the putamen are particularly important, respectively, in the planning and the
      execution of a self-generated novel action, whereas the subthalamic nucleus may
      be required when a new motor program is solicited independently of the choice of
      strategy.

PMID- 16437583
TI  - Severe episodic neurological deficits and permanent mental retardation in a child
      with a novel FHM2 ATP1A2 mutation.
AB  - OBJECTIVE: Attacks of familial hemiplegic migraine (FHM) are usually associated
      with transient, completely reversible symptoms. Here, we studied the ATP1A2 FHM2
      gene in a young girl with episodes of both very severe and transient neurological
      symptoms that were triggered by mild head trauma as well as permanent mental
      retardation. Her family members suffered from hemiplegic and confusional migraine
      attacks. METHODS: Mutation analysis of the ATP1A2 gene was performed by direct
      sequencing of all exons and flanking intronic regions, using genomic DNA of the
      proband. Functional consequences of the mutation were analyzed by cellular
      survival assays. RESULTS: We identified a novel G615R ATP1A2 mutation in the
      proband and several of her family members. Functional analysis of mutant Na,K
      ATPase in cellular survival assays showed a complete loss-of-function effect.
      INTERPRETATION: Permanent mental retardation in children may be caused by ATP1A2
      mutations.

PMID- 16437584
TI  - Biochemical and pathological characterization of Lrrk2.
AB  - OBJECTIVE: Mutations in leucine-rich repeat kinase 2 (LRRK2) recently have been
      identified as the most common genetic cause of late-onset sporadic and familial
      Parkinson's disease (PD). The studies herein explore the biological and
      pathological properties of Lrrk2. METHODS: Genetic analysis was performed to
      identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using
      an antibody specific to Lrrk2, the biochemical and immunocytochemical
      distribution of Lrrk2 was assessed. RESULTS: Three patients with the G2019S Lrrk2
      mutation were identified. Two patients demonstrated classic PD with Lewy bodies,
      although concurrent pathological changes consistent with Alzheimer's disease were
      also present in one of these individuals. The third patient was characterized by
      parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the
      substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to
      this patient and Lrrk2 was not detected in other types of pathological
      inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble
      approximately 250 kDa cytoplasmic protein expressed throughout the brain but also
      in many other organs. INTERPRETATION: The reasons for the selective
      predisposition of patients with mutations in LRRK2 to develop parkinsonism
      remains unclear, but Lrrk2 mutations may prime select neuronal populations to
      cellular insults that can lead to aberrant protein aggregation.

PMID- 16437585
TI  - Coadministration of entacapone with levodopa attenuates the severity of
      dyskinesias in hemiparkinsonian rats.
AB  - Levodopa-induced dyskinesias (LIDs) have been associated with a sequence of
      events that includes pulsatile stimulation of dopamine receptors. The degree of
      nigrostriatal degeneration, the half-life of dopaminomimetic agents, and the dose
      of levodopa used to treat parkinsonian symptoms are factors directly correlated
      with the development of motor complications in Parkinson's disease patients. Long
      acting agents producing continuous dopaminergic stimulation are less likely to
      prime for dyskinesia than short-acting drugs that produce pulsatile stimulation
      of dopamine receptors. Inhibition of the enzyme catechol-O-methyl transferase
      (COMT) by entacapone extends the half-life of levodopa and minimizes variability
      in plasma levodopa levels. The aim of the present study was to characterize the
      effect of the early administration of the COMT inhibitor entacapone in the
      recently described model of LIDs in rats with a nigrostriatal lesion induced by 6
      hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a unilateral 6-OHDA
      administration in the nigrostriatal pathway. Animals were treated either with
      levodopa (6 mg/kg, twice at day, i.p.) plus entacapone (30 mg/kg per day, i.p.)
      or levodopa (6 mg/kg, twice at day, i.p.) plus vehicle for 22 consecutive days.
      Early administration of entacapone, in association with levodopa, induces a
      decrease in the severity of dyskinesia and delays their onset in hemiparkinsonian
      rats. All dyskinesia subtypes evaluated, such as axial, limb, and orofacial
      dyskinesias, have shown similar reductions. These results suggest that
      entacapone, by extending levodopa elimination half-life, might reduce its
      propensity to induce motor complications.

PMID- 16437586
TI  - Did Gustav Mahler have Sydenham's chorea?
AB  - Sydenham's chorea (SC), a major manifestation of acute rheumatic fever (RF), is
      characterized by chorea and other motor and non-motor features. Among the latter
      are behavioral symptoms, including obsessive-compulsive disorder. Although SC is
      typically a self-limited condition, up to 50% of patients may evolve with
      persistent chorea. There is evidence that Gustav Mahler had a movement disorder,
      but its nature remains undetermined. There are witnesses describing him as having
      facial dyskinesia and a gait disorder consistent with chorea. His conducting
      performance was notorious for obsessive attention to details of the staging and
      musical production. Mahler was diagnosed with a valvulopathy in 1907 and died of
      subacute bacterial endocarditis in 1911. It is possible that the composer
      suffered from RF in childhood with carditis and SC, which may left him with
      valvulopathy, obsessive-compulsive disorder, and persistent chorea.

PMID- 16437587
TI  - Using endophenotypes for pathway clusters to map complex disease genes.
AB  - Nature determines the complexity of disease etiology and the likelihood of
      revealing disease genes. While culprit genes for many monogenic diseases have
      been successfully unraveled, efforts to map major complex disease genes have not
      been as productive as hoped. The conceptual framework currently adopted to deal
      with the heterogeneous nature of complex diseases focuses on using homogeneous
      internal features of the disease phenotype for mapping. However, phenotypic
      homogeneity does not equal genotypic homogeneity. In this report, we advocate
      working with well-measured phenotypes portrayed by amounts of transcripts and
      activities of gene products or their metabolites, which are pertinent to
      relatively small pathway clusters. Reliable and controlled measures for
      oligogenic traits resulting from proper dissection efforts may enhance
      statistical power. The large amounts of information obtained on gene and protein
      expression from technological advances can add to the power of gene finding,
      particularly for diseases with unclear etiology. Data-mining tools for dimension
      reduction can assist biologists to reveal novel molecular endophenotypes.
      However, there are still hurdles to overcome, including high cost, relatively
      poor reproducibility and comparability among platforms, the cross-sectional
      nature of the information, and the accessibility of human tissues. Concerted
      efforts are required to carry out large-scale prospective studies that are
      integrated at the levels of phenotype characterization, high throughput
      experimental techniques, data analyses, and beyond.

PMID- 16437588
TI  - Parkinsonism associated with basal ganglia cryptococcal abscesses in an
      immunocompetent patient.
AB  - Currently, infectious agents are a rare cause of parkinsonism. We report on an
      immunocompetent patient with persistent parkinsonism associated with cryptococcal
      abscesses of the basal ganglia.

PMID- 16437589
TI  - Primary focal lingual dystonia.

PMID- 16437590
TI  - Clinicopathological study of cardiac tamponade due to pericardial metastasis
      originating from gastric cancer.
AB  - AIM: To review the cases reported in the literature, examined their
      clinicopathological features, and evaluated the efficacy of different therapeutic
      modalities for this rare condition. METHODS: A search of the MEDLINE database
      revealed 16 cases of pericarditis carcinomatosa (PC) originating from GC reported
      in the literature between 1982 and 2005. Additional detailed data were obtained
      from the authors of these studies for subsequent clinicopathological
      investigation. We have also described about a case study from our own clinic.
      RESULTS: The mean age of cases with pericarditis carcinomatosa originating from
      GC was 54 years. Females were diagnosed at a younger age (46.3 years) compared to
      males (58 years). The mean survival period after diagnosis was 4.5 mo. No
      statistical differences in the length of survival time were found between
      different therapeutic modalities, such as drainage, and local and/or systemic
      chemotherapy after drainage. However, three cases who underwent systemic
      chemotherapy survived for more than 10 mo. Cases that developed metachronous
      cardiac tamponade for more than 2 years after the diagnosis of GC generally
      survived for a longer period of time, although this was not statistically
      significant. Multivariate analysis revealed that low levels of carcinoembryonic
      antigen (CEA), and CEA and/or cancer antigen 19-9 (CA 19-9) were associated with
      longer survival. CONCLUSION: Cases with low levels of CEA, and CEA and/or CA 19-9
      should undergo systemic chemotherapy with or without local chemotherapy after
      drainage.

PMID- 16437591
TI  - Significance of a novel sucrose permeability test using serum in the diagnosis of
      early gastric cancer.
AB  - AIM: To investigate the usefulness of sucrose permeability test using serum in
      the diagnosis of gastric diseases, with special reference to early gastric cancer
      (EGC). METHODS: A total of 63 subjects, including 11 patients with gastric ulcer,
      20 patients with gastric cancer (13, early; 7, advanced) and 32 healthy controls,
      were studied. Blood and urine samples were collected repeatedly for 5 h before
      and after the sucrose loading. Sucrose levels were measured by a newly developed
      enzymatic method. RESULTS: Serum sucrose levels started to increase 15 min after
      loading, and peaked at 60 min in the gastric disease groups. The levels for
      gastric ulcer, EGC and advanced gastric cancer (AGC) at 60 min were significantly
      higher than that in the healthy controls (26.9+/-2.4, 34.4+/-5.0, and 71.8+/-15.6
      vs 7.9+/-0.7 mol/L, respectively, P<0.01). The cut-off level set at 15.4 mol/L
      (60 min) offered the best distinction between EGC patients and healthy controls;
      and the sensitivity and specificity were 92.3% and 93.8%, respectively, while
      those of the urine method were 76.9% and 93.8%, respectively. CONCLUSIONS: The
      gastric permeability test using serum is reliable for the detection of EGC, and
      this test can provide results much earlier than the conventional urine method.
      This test may offer a useful alternative to more invasive tests for EGC.

PMID- 16437592
TI  - Bifunctional chimeric SuperCD suicide gene -YCD: YUPRT fusion is highly effective
      in a rat hepatoma model.
AB  - AIM: To investigate the effects of catalytically superior gene-directed enzyme
      prodrug therapy systems on a rat hepatoma model. METHODS: To increase hepatoma
      cell chemosensitivity for the prodrug 5-fluorocytosine (5-FC), we generated a
      chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine
      deaminase (YCD) and the yeast uracil phosphoribosyltransferase (YUPRT) gene.
      RESULTS: In vitro stably transduced Morris rat hepatoma cells (MH) expressing the
      bifunctional SuperCD suicide gene (MH SuperCD) showed a clearly marked
      enhancement in cell killing when incubated with 5-FC as compared with MH cells
      stably expressing YCD solely (MH YCD) or the cytosine deaminase gene of bacterial
      origin (MH BCD), respectively. In vivo, MH SuperCD tumors implanted both
      subcutaneously as well as orthotopically into the livers of syngeneic ACI rats
      demonstrated significant tumor regressions (P<0.01) under both high dose as well
      as low dose systemic 5-FC application, whereas MH tumors without transgene
      expression (MH naive) showed rapid progression. For the first time, an order of
      in vivo suicide gene effectiveness (SuperCD>> YCD>>BCD>>>negative control) was
      defined as a result of a direct in vivo comparison of all three suicide genes.
      CONCLUSION: Bifunctional SuperCD suicide gene expression is highly effective in a
      rat hepatoma model, thereby significantly improving both the therapeutic index
      and the efficacy of hepatocellular carcinoma killing by fluorocytosine.

PMID- 16437593
TI  - Role of blood AFP mRNA and tumor grade in the preoperative prognostic evaluation
      of patients with hepatocellular carcinoma.
AB  - AIM: To explore the potential prognostic role of preoperative tumor grade and
      blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC)
      eligible for radical therapies according to a well-defined treatment algorithm
      not including nodule size and number as absolute selection criteria. METHODS:
      Fifty patients with a diagnosis of HCC were prospectively enrolled in the study.
      Inclusion criteria were: (1) histological assessment of tumor grade by means of
      percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3)
      patient's eligibility for radical therapies. RESULTS: At preoperative evaluation,
      54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the
      blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery
      (resection or liver transplantation) was performed in 29 patients, while 21 had
      percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-,
      and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy,
      performance status and three tumor-related variables (AFP mRNA, HCC grade and
      gross vascular invasion) resulted as significant survival predictors at
      univariate analysis. Nodule size and number did not perform as significant
      prognosticators. Multivariate study selected only surgical therapy and a
      biologically early HCC profile (AFP mRNA negative and well-differentiated tumor
      without gross vascular invasion) as independent survival variables. CONCLUSION:
      The preoperative determination of tumor grade and blood AFP mRNA status may
      potentially refine the prognostic evaluation of HCC patients and improve the
      selection process for radical therapies.

PMID- 16437594
TI  - Etiology and functional status of liver cirrhosis by 31P MR spectroscopy.
AB  - AIM: To assess the functional status and etiology of liver cirrhosis by
      quantitative (31)P magnetic resonance spectroscopy (MRS). METHODS: A total of 80
      patients with liver cirrhosis of different etiology and functional status
      described by Child-Pugh score were examined and compared to 11 healthy
      volunteers. MR examination was performed on a 1.5 T imager using a (1)H/(31)P
      surface coil by the 2D chemical shift imaging technique. Absolute concentrations
      of phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and
      adenosine triphosphate (ATP) were measured. RESULTS: MRS changes reflected the
      degree of liver dysfunction in all the patients as well as in individual
      etiological groups. The most important change was a decrease of PDE. It was
      possible to distinguish alcoholic, viral and cholestatic etiologies based on MR
      spectra. Alcoholic and viral etiology differed in PDE (alcoholic, viral,
      controls: 6.5+/-2.3, 6.5+/-3.1, 10.8+/-2.7 mmol/L, P<0.001) and ATP (alcoholic,
      viral, controls: 2.9+/-0.8, 2.8+/-0.9, 3.7+/-1.0 mmol/L, P<0.01) from the control
      group. Unlike viral etiology, patients with alcoholic etiology also differed in
      Pi (alcoholic, controls: 1.2+/-0.4, 1.6+/-0.6 mmol/L, P<0.05) from controls. No
      significant changes were found in patients with cholestatic disease and controls;
      nevertheless, this group differed from both alcoholic and viral groups
      (cholestatic, alcoholic, viral: 9.4+/-2.7, 6.5+/-2.3, 6.5+/-3.1 mmol/L, P<0.005)
      in PDE. CONCLUSION: (31)P MRS can significantly help in non-invasive separation
      of different etiological groups leading to liver cirrhosis. In addition, MRS
      changes reflect functional liver injury.

PMID- 16437595
TI  - Three-dimensional computed tomography in laparoscopic surgery for colorectal
      carcinoma.
AB  - AIM: To evaluate the usefulness of three-dimensional computed tomography (3DCT)
      in laparoscopic surgery for colorectal carcinoma. METHODS: Seventy-two patients
      with colorectal cancer who underwent curative operation at our hospital were
      enrolled in this study. They were classified into two groups by operative
      procedures. Sixteen patients underwent laparoscopic surgery, laparoscopic group
      (LG), while 56 patients underwent conventional open surgery, open group (OG). At
      our institution, contrast-enhanced CT is routinely performed as part of intra
      abdominal screening and the 3D images of the major regional vessels are
      described. We have previously described about the preoperative visualization of
      the inferior mesenteric artery (IMA) by 3DCT. This time we newly acquired 3D
      images of the superior mesenteric artery (SMA)/superior mesenteric vein (SMV),
      ileocecal artery (ICA), middle colic artery (MCA), and inferior mesenteric vein
      (IMV). We have compared our two study groups with regard to five items, including
      clinical anastomotic leakage. We have discussed here the role of 3DCT in
      laparoscopic surgery for colorectal carcinoma. RESULTS: The mean length of the
      incision in LG was 4.625+/-0.89 cm, which was significantly shorter than that in
      OG (P<0.001). The association between ICA and SMV and SMA was described in the
      right-sided colectomy. The preoperative imaging of IMA and IMV was created in the
      rectosigmoidectomy. There was no significant difference in anastomotic leakage
      between the two groups, but no patients in LG experienced anastomotic leakage.
      CONCLUSION: Most of the patients are satisfied with the shorter incisional length
      following laparoscopic surgery. Preoperative visualization of the major regional
      vessels may be helpful for the secure treatment of the anastomosis in
      laparoscopic surgery for colorectal carcinoma.

PMID- 16437597
TI  - Clinical significance of telomerase and its associate genes expression in the
      maintenance of telomere length in squamous cell carcinoma of the esophagus.
AB  - AIM: To observe the interaction between the expression of telomerase activity
      (TA) and its associate genes in regulation of the terminal restriction fragment
      length (TRFL) in esophageal squamous cell carcinoma (SCC). METHODS: Seventy-four
      specimens of esophageal SCC were examined. The TA was measured by telomeric
      repeat amplification protocol (TRAP) assay, and the associated genes [human
      telomerase-specific reverse transcriptase (hTERT), hTERC, TP1, c-Myc, TRF1, and
      TRF2] were detected using RT-PCR method. The TRFL was measured by Telomere Length
      Assay Kit and Southern blotting. The correlations between the expression of
      telomerase and its associated genes with the TRFL and survivals were examined.
      RESULTS: Expressions of the TA, hTERT, hTERC, TP1, c-Myc, TRF1, and TRF2 genes
      were observed in 85.1%, 64.9%, 79.7%, 100.0%, 94.6%, 82.4%, and 91.9% of the
      tumor tissues, respectively. The TRFL of the tumor and normal esophageal tissues
      were 2.70+/-1.42 and 4.93+/-1.74 kb, respectively (P<0.0001). The TRFL of the
      telomerase positive and telomerase negative tumor tissues were 2.72+/-1.44 and
      2.58+/-1.32 kb, respectively (P = 0.767). The TRFL ratios (TRFLR) of the
      telomerase positive and telomerase negative tumor tissues were 0.55+/-0.22 and
      0.59+/-0.41, respectively (P = 0.742). The expression rates of h-TERT (P =
      0.0002), hTERC (P<0.0001), and TRF1 (P = 0.002) in the tumor tissues are higher
      than those of the normal paired tissues. Though TA is markedly activated in tumor
      tissues (P<0.0001), its expression is not related to clinicopathological
      parameters including gender, tumor differentiation, and TNM stages. The
      cumulative 4-year survival rates of telomerase positive and telomerase negative
      cases were 35.86% and 31.2%, respectively (P = 0.8442). The cumulative 4-year
      survival rates of patients with their TRFLR <or=85% and >85% were 38.7% and
      15.7%, respectively (P = 0.1307). CONCLUSION: Though telomerase expression is not
      related to tumor stages and prognosis, our data support that the TA increased as
      the TRFL decreased, probably under the control of hTERT, hTERC, and TRF1. When
      telomerase expression was activated, only TRF2 overexpression persisted to
      stabilize T-loop formation. Furthermore, as the TRFLR decreased to 85%, a trend
      of better prognosis was observed. Cox model analysis indicates a higher t/n TRFLR
      and distant metastasis are independent poorer prognostic factors (P = 0.035 and P
      = 0.042, respectively).

PMID- 16437596
TI  - Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease
      progression in murine hepatitis virus type 3-induced fulminant hepatitis and in
      patients with severe viral hepatitis B.
AB  - AIM: To evaluate the expression of fibrinogen-like protein 2 (fgl2) and its
      correlation with disease progression in both mice and patients with severe viral
      hepatitis. METHODS: Balb/cJ or A/J mice were infected intraperitoneally (ip) with
      100 PFU of murine hepatitis virus type 3 (MHV-3), liver and serum were harvested
      at 24, 48, and 72 h post infection for further use. Liver tissues were obtained
      from 23 patients with severe acute chronic (AOC) hepatitis B and 13 patients with
      mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with
      cirrhosis and 4 liver donors served as normal controls. In addition, peripheral
      blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with
      severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant
      activity representing functional prothrombinase activity in PBMC and white blood
      cells was also assayed. A polyclonal antibody against fgl2 was used to detect the
      expression of both mouse and human fgl2 protein in liver samples as well as in
      PBMC by immunohistochemistry staining in a separate set of studies. Alanine
      aminotransferase (ALT) and total bilirubin (TBil) in serum were measured to
      assess the severity of liver injury. RESULTS: Histological changes were found in
      liver sections 12-24 h post MHV-3 infection in Balb/cJ mice. In association with
      changes in liver histology, marked elevations in serum ALT and TBil were
      observed. Mouse fgl2 (mfgl2) protein was detected in the endothelium of
      intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3
      infection. Liver tissues from the patients with severe AOC hepatitis B had
      classical pathological features of acute necroinflammation. Human fgl2 (hfgl2)
      was detected in 21 of 23 patients (91.30%) with severe AOC hepatitis B, while
      only 1 of 13 patients (7.69%) with mild chronic hepatitis B and cirrhosis had
      hfgl2 mRNA or protein expression. Twenty-eight of thirty patients (93.33%) with
      severe AOC hepatitis B and 1 of 10 with mild chronic hepatitis B had detectable
      hfgl2 expression in PBMC. No hfgl2 expression was found either in the liver
      tissue or in the PBMC from normal donors. There was a positive correlation
      between hfgl2 expression and the severity of the liver disease as indicated by
      the levels of TBil. PCA significantly increased in PBMC in patients with severe
      AOC hepatitis B. CONCLUSION: The molecular and cellular results reported here in
      both mice and patients with severe viral hepatitis suggest that virus-induced
      hfgl2 prothrombinase/fibroleukin expression and the coagulation activity
      associated with the encoded fgl2 protein play a pivotal role in initiating severe
      hepatitis. The measurement of hfgl2/fibroleukin expression in PBMC may serve as a
      useful marker to monitor the severity of AOC hepatitis B and a target for
      therapeutic intervention.

PMID- 16437598
TI  - Relationship between body surface area and ALT normalization after long-term
      lamivudine treatment.
AB  - AIM: To further evaluate the relationship between BSA and the effects of
      lamivudine in a greater number of cases and over a longer period of observation
      than in our previous evaluation. METHODS: We evaluated 249 patients with chronic
      hepatitis B. The effects of treatment for one year (n = 249), two years (n =
      147), and three years (n = 72) were evaluated from the levels of serum ALT and
      HBV-DNA, as biological and virological effects (undetectable levels by PCR),
      respectively. Moreover, several variables that could influence the response to
      treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBV-DNA, and
      HBeAg were analyzed. RESULTS: For 1-year treatment, multivariate analysis
      revealed that BSA (P = 0.0002) was the only factor for the biological effect, and
      that ALT (P = 0.0017), HBV-DNA (P = 0.0004), and HBeAg (P = 0.0021) were
      independent factors for the virological effect. For 2-year treatment,
      multivariate analysis again showed that BSA (P = 0.0147) was the only factor for
      the biological effect, and that ALT (P = 0.0192) and HBeAg (P = 0.0428) were
      independent factors for the virological effect. For 3-year treatment,
      multivariate analysis, however, could not reveal BSA (P = 0.0730) as a factor for
      the normalization of ALT levels. CONCLUSION: BSA is a significant predictor for
      the normalizing the effect of lamivudine therapy on ALT for an initial 2-year
      period, suggesting that lamivudine dosage should be based on the individual BSA.

PMID- 16437599
TI  - Excessive portal flow causes graft failure in extremely small-for-size liver
      transplantation in pigs.
AB  - AIM: To evaluate the effects of a portocaval shunt on the decrease of excessive
      portal flow for the prevention of sinusoidal microcirculatory injury in extremely
      small-for-size liver transplantation in pigs. METHODS: The right lateral lobe of
      pigs, i.e. the 25% of the liver, was transplanted orthotopically. The pigs were
      divided into two groups: graft without portocaval shunt (n = 11) and graft with
      portocaval shunt (n = 11). Survival rate, portal flow, hepatic arterial flow, and
      histological findings were investigated. RESULTS: In the group without portocaval
      shunt, all pigs except one died of liver dysfunction within 24 h after
      transplantation. In the group with portocaval shunt, eight pigs survived for more
      than 4 d. The portal flow volumes before and after transplantation in the group
      without portocaval shunt were 118.2+/-26.9 mL/min/100 g liver tissue and 270.5+/
      72.9 mL/min/100 g liver tissue, respectively. On the other hand, in the group
      with portocaval shunt, those volumes were 124.2+/-27.8 mL/min/100 g liver tissue
      and 42.7+/-32.3 mL/min/100 g liver tissue, respectively (P<0.01). As for
      histological findings in the group without portocaval shunt, destruction of the
      sinusoidal lining and bleeding in the peri-portal areas were observed after
      reperfusion, but these findings were not recognized in the group with portocaval
      shunt. CONCLUSION: These results suggest that excessive portal flow is attributed
      to post transplant liver dysfunction after extreme small-for-size liver
      transplantation caused by sinusoidal microcirculatory injury.

PMID- 16437600
TI  - Nuclear factor-kappaB decoy oligodeoxynucleotides attenuates ischemia/reperfusion
      injury in rat liver graft.
AB  - AIM: To evaluate the protective effect of NF-kappaB decoy oligodeoxynucleotides
      (ODNs) on ischemia/reperfusion (I/R) injury in rat liver graft. METHODS:
      Orthotopic syngeneic rat liver transplantation was performed with 3 h of cold
      preservation of liver graft in University of Wisconsin solution containing
      phosphorothioated double-stranded NF-kappaB decoy ODNs or scrambled ODNs. NF
      kappaB decoy ODNs or scrambled ODNs were injected intravenously into donor and
      recipient rats 6 and 1 h before operation, respectively. Recipients were killed 0
      to 16 h after liver graft reperfusion. NF-kappaB activity in the liver graft was
      analyzed by electrophoretic mobility shift assay (EMSA). Hepatic mRNA expression
      of TNF-alpha, IFN-gamma and intercellular adhesion molecule-1 (ICAM-1) were
      determined by semiquantitative RT-PCR. Serum levels of TNF-alpha and IFN-gamma
      were measured by enzyme-linked immunosorbent assays (ELISA). Serum level of
      alanine transaminase (ALT) was measured using a diagnostic kit. Liver graft
      myeloperoxidase (MPO) content was assessed. RESULTS: NF-kappaB activation in
      liver graft was induced in a time-dependent manner, and NF-kappaB remained
      activated for 16 h after graft reperfusion. NF-kappaB activation in liver graft
      was significant at 2 to 8 h and slightly decreased at 16 h after graft
      reperfusion. Administration of NF-kappaB decoy ODNs significantly suppressed NF
      kappaB activation as well as mRNA expression of TNF-alpha, IFN-gamma and ICAM-1
      in the liver graft. The hepatic NF-kappaB DNA binding activity [presented as
      integral optical density (IOD) value] in the NF-kappaB decoy ODNs treatment group
      rat was significantly lower than that of the I/R group rat (2.16+/-0.78 vs
      36.78+/-6.35 and 3.06+/-0.84 vs 47.62+/- 8.71 for IOD value after 4 and 8 h of
      reperfusion, respectively, P<0.001). The hepatic mRNA expression level of TNF
      alpha, IFN-gamma and ICAM-1 [presented as percent of beta-actin mRNA (%)] in the
      NF-kappaB decoy ODNs treatment group rat was significantly lower than that of the
      I/R group rat (8.31+/-3.48 vs 46.37+/-10.65 and 7.46+/- 3.72 vs 74.82+/-12.25 for
      hepatic TNF-alpha mRNA, 5.58+/-2.16 vs 50.46+/-9.35 and 6.47+/-2.53 vs 69.72+/
      13.41 for hepatic IFN-gamma mRNA, 6.79+/-2.83 vs 46.23+/-8.74 and 5.28+/-2.46 vs
      67.44+/-10.12 for hepatic ICAM-1 mRNA expression after 4 and 8 h of reperfusion,
      respectively, P<0.001). Administration of NF-kappaB decoy ODNs almost completely
      abolished the increase of serum level of TNF-alpha and IFN-gamma induced by
      hepatic ischemia/reperfusion, the serum level (pg/mL) of TNF-alpha and IFN-gamma
      in the NF-kappaB decoy ODNs treatment group rat was significantly lower than that
      of the I/R group rat (42.7+/-13.6 vs 176.7+/-15.8 and 48.4+/-15.1 vs 216.8+/-17.6
      for TNF-alpha level, 31.5+/-12.1 vs 102.1+/-14.5 and 40.2+/-13.5 vs 118.6+/-16.7
      for IFN-gamma level after 4 and 8 h of reperfusion, respectively, P<0.001). Liver
      graft neutrophil recruitment indicated by MPO content and hepatocellular injury
      indicated by serum ALT level were significantly reduced by NF-kappaB decoy ODNs,
      the hepatic MPO content (A655) and serum ALT level (IU/L) in the NF-kappaB decoy
      ODNs treatment group rat was significantly lower than that of the I/R group rat
      (0.17+/-0.07 vs 1.12+/-0.25 and 0.46+/-0.17 vs 1.46+/-0.32 for hepatic MPO
      content, 71.7+/-33.2 vs 286.1+/-49.6 and 84.3+/-39.7 vs 467.8+/-62.3 for ALT
      level after 4 and 8 h of reperfusion, respectively, P<0.001). CONCLUSION: The
      data suggest that NF-kappaB decoy ODNs protects against I/R injury in liver graft
      by suppressing NF-kappaB activation and subsequent expression of proinflammatory
      mediators.

PMID- 16437601
TI  - Induction of pancreatic duct cells of neonatal rats into insulin-producing cells
      with fetal bovine serum: a natural protocol and its use for patch clamp
      experiments.
AB  - AIM: To induce the pancreatic duct cells into endocrine cells with a new natural
      protocol for electrophysiological study. METHODS: The pancreatic duct cells of
      neonatal rats were isolated, cultured and induced into endocrine cells with 15%
      fetal bovine serum for a period of 20 d. During this period, insulin secretion,
      MTT value, and morphological change of neonatal and adult pancreatic islet cells
      were comparatively investigated. Pancreatic beta-cells were identified by
      morphological and electrophysiological characteristics, while ATP sensitive
      potassium channels (K(ATP)), voltage-dependent potassium channels (K(V)), and
      voltage-dependent calcium channels (K(CA)) in beta-cells were identified by patch
      clamp technique. RESULTS: After incubation with fetal bovine serum, the neonatal
      duct cells budded out, changed from duct-like cells into islet clusters. In the
      first 4 d, MTT value and insulin secretion increased slowly (MTT value from
      0.024+/-0.003 to 0.028+/-0.003, insulin secretion from 2.6+/-0.6 to 3.1+/-0.8
      mIU/L). Then MTT value and insulin secretion increased quickly from d 5 to d 10
      (MTT value from 0.028+/-0.003 to 0.052+/-0.008, insulin secretion from 3.1+/-0.8
      to 18.3+/-2.6 mIU/L), then reached high plateau (MTT value >0.052+/-0.008,
      insulin secretion >18.3+/-2.6 mIU/L). In contrast, for the isolated adult
      pancreatic islet cells, both insulin release and MTT value were stable in the
      first 4 d (MTT value from 0.029+/-0.01 to 0.031+/-0.011, insulin secretion from
      13.9+/-3.1 to 14.3+/-3.3 mIU/L), but afterwards they reduced gradually (MTT value
      <0.031+/-0.011, insulin secretion <8.2+/-1.5 mIU/L), and the pancreatic islet
      cells became dispersed, broken or atrophied correspondingly. The differentiated
      neonatal cells were identified as pancreatic islet cells by dithizone staining
      method, and pancreatic beta-cells were further identified by both morphological
      features and electrophysiological characteristics, i.e. the existence of
      recording currents from K(ATP), K(V), and K(CA). CONCLUSION: Islet cells
      differentiated from neonatal pancreatic duct cells with the new natural protocol
      are more advantageous in performing patch clamp study over the isolated adult
      pancreatic islet cells.

PMID- 16437602
TI  - Oral vaccination of mice against rodent malaria with recombinant Lactococcus
      lactis expressing MSP-1(19).
AB  - AIM: To construct the recombinant Lactococcus lactis as oral delivery vaccination
      against malaria. METHODS: The C-terminal 19-ku fragments of MSP1 (MSP-1(19)) of
      Plasmodium yoelii 265-BY was expressed in L. lactis and the recombinant L. lactis
      was administered orally to BALB/c and C57BL/6 mice. After seven interval
      vaccinations within 4 wk, the mice were challenged with P. yoelii 265-BY
      parasites of erythrocytic stage. The protective efficacy of recombinant L. lactis
      was evaluated. RESULTS: The peak parasitemias in average for the experiment
      groups of BALB/c and C57BL/6 mice were 0.8+/-0.4% and 20.8+/-26.5%, respectively,
      and those of their control groups were 12.0+/-0.8% and 60.8+/-9.6%, respectively.
      None of the BALB/c mice in both experimental group and control group died during
      the experiment. However, all the C57BL/6 mice in the control group died within 23
      d and all the vaccinated mice survived well. CONCLUSION: The results imply the
      potential of recombinant L. lactis as oral delivery vaccination against malaria.

PMID- 16437603
TI  - Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced
      damage in intestinal epithelium via regulating P53 and P21WAF-1 expression.
AB  - AIM: To detect the effect of acid fibroblast growth factor (aFGF) on P53 and
      P21WAF-1 expression in rat intestine after ischemia-reperfusion (I-R) injury in
      order to explore the protective mechanisms of aFGF. METHODS: Male rats were
      randomly divided into four groups, namely intestinal ischemia-reperfusion group
      (R), aFGF treatment group (A), intestinal ischemia group (I), and sham-operated
      control group (C). In group I, the animals were killed after 45 min of superior
      mesenteric artery (SMA) occlusion. In groups R and A, the rats sustained for 45
      min of SMA occlusion and were treated with normal saline (0.15 mL) and aFGF (20
      mug/kg, 0.15 mL), then sustained at various times for up to 48 h after
      reperfusion. In group C, SMA was separated, but without occlusion. Apoptosis in
      intestinal villi was determined with terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick-end labeling technique (TUNEL). Intestinal tissue
      samples were taken not only for RT-PCR to detect P53 and P21WAF-1 gene
      expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1
      protein expression and distribution. RESULTS: In histopathological study,
      ameliorated intestinal structures were observed at 2, 6, and 12 h after
      reperfusion in A group compared to R group. The apoptotic rates were (41.17+/
      3.49)%, (42.83+/-5.23)%, and (53.33+/-6.92)% at 2, 6, and 12 h after reperfusion,
      respectively in A group, which were apparently lower than those in R group at
      their matched time points (50.67+/-6.95)%, (54.17+/-7.86)%, and (64.33+/-6.47)%,
      respectively, (P<0.05)). The protein contents of P53 and P21WAF-1 were both
      significantly decreased in A group compared to R group (P<0.05) at 2-12 h after
      reperfusion, while the mRNA levels of P53 and P21WAF-1 in A group were obviously
      lower than those in R group at 6-12 h after reperfusion (P<0.05). CONCLUSION: P53
      and P21WAF-1 protein accumulations are associated with intestinal barrier injury
      induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat
      intestinal cells by inhibiting P53 and P21WAF-1 protein expression.

PMID- 16437604
TI  - Anti-Saccharomyces cerevisiae antibody titers are stable over time in Crohn's
      patients and are not inducible in murine models of colitis.
AB  - AIM: To investigate ASCA production over time in CD and murine colitis in order
      to further our understanding of their etiology. MATERIALS AND METHODS: Sixty-six
      CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome
      patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA
      positivity as well as change in titers over a period of up to 3 years (Delta
      IgG/A) was correlated with clinical parameters such as CD activity index (CDAI)
      and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS
      and IL-10 knock out) were compared to control animals with respect to ASCA titers
      after oral yeast exposure. RESULTS: ASCA IgG and IgA titers are stable over time
      in CD and non-CD patients. Fistular disease was associated with a higher rate of
      ASCA IgA positivity (P = 0.014). Ileal disease was found to have a significant
      influence on the Delta IgG of ASCA (P = 0.032). There was no correlation found
      between ASCA positivity or Delta IgG/A and clinical parameters of CD: CDAI and
      CRP. In mice, neither healthy animals nor animals with DSS-induced or spontaneous
      colitis exhibited a marked increase in ASCA titers after high-dose yeast
      exposure. On the other hand, mice immunized intraperitoneally with mannan plus
      adjuvant showed a marked and significant increase in ASCA titers compared to
      adjuvant-only immunized controls (P = 0.014). CONCLUSION: The propensity to
      produce ASCA in a subgroup of CD patients is largely genetically predetermined as
      evidenced by their stability and lack of correlation with clinical disease
      activity parameters. Furthermore, in animal models of colitis, mere oral exposure
      of mice to yeast does not lead to the induction of marked ASCA titers
      irrespective of concomitant colonic inflammation. Hence, environment may play
      only a minor role in inducing ASCA.

PMID- 16437605
TI  - Computer-aided morphometry of liver inflammation in needle biopsies.
AB  - AIM: To introduce a computer-aided morphometric method for quantifying the necro
      inflammatory phase in liver biopsy specimens using fractal geometry and
      Delaunay's triangulation. METHODS: Two-micrometer thick biopsy sections taken
      from 78 chronic hepatitis C virus-infected patients were immunohistochemically
      treated to identify the inflammatory cells. An automatic computer-aided image
      analysis system was used to define the inflammatory cell network defined on the
      basis of Delaunay's triangulation, and the inflammatory cells were geometrically
      classified as forming a cluster (an aggregation of a minimum of three cells) or
      as being irregularly distributed within the tissue. The phase of inflammatory
      activity was estimated using Hurst's exponent. RESULTS: The proposed automatic
      method was rapid and objective. It could not only provide rigorous results
      expressed by scalar numbers, but also allow the state of the whole organ to be
      represented by Hurst's exponent with an error of no more than 12%. CONCLUSION:
      The availability of rigorous metrical measures and the reasonable
      representativeness of the status of the organ as a whole raise the question as to
      whether the indication for hepatic biopsy should be revised by establishing clear
      rules concerning the contraindications suggested by its invasiveness and
      subjective interpretation.

PMID- 16437606
TI  - Open label trial of granulocyte apheresis suggests therapeutic efficacy in
      chronically active steroid refractory ulcerative colitis.
AB  - AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive
      type apheresis system for the treatment of patients with chronically active
      ulcerative colitis despite standard therapy. METHODS: An open label multicenter
      study was carried out in 39 patients with active ulcerative colitis (CAI 6-8)
      despite continuous use of steroids (a minimum total dose of 400 mg prednisone
      within the last 4 wk). Patients received a total of five aphereses using a
      granulocyte adsorptive technique (Adacolumn (reg), Otsuka Pharmaceutical Europe,
      UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI)
      and endoscopic (EI) activity index, histology, quality of life (IBDQ), and
      laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified
      for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35
      (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had
      endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased
      significantly (24 points, P<0.01) at wk 6. Apheresis could be performed in all
      but one patient. Aphereses were well tolerated, only one patient experienced
      anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five
      aphereses with a granulocyte/monocyte depleting filter show potential short-term
      efficacy. Tolerability and technical feasibility of the procedure are excellent.

PMID- 16437607
TI  - Appropriateness of indication and diagnostic yield of colonoscopy: first report
      based on the 2000 guidelines of the American Society for Gastrointestinal
      Endoscopy.
AB  - AIM: To assess the appropriateness of referrals and to determine the diagnostic
      yield of colonoscopy according to the 2000 guidelines of the American Society for
      Gastrointestinal Endoscopy (ASGE). METHODS: A total of 736 consecutive patients
      (415 males, 321 females; mean age 43.6+/-16.6 years) undergoing colonoscopy
      during October 2001-March 2002 were prospectively enrolled in the study. The 2000
      ASGE guidelines were used to assess the appropriateness of the indications for
      the procedure. Diagnostic yield was defined as the ratio between significant
      findings detected on colonoscopy and the total number of procedures performed for
      that indication. RESULTS: The large majority (64%) of patients had colonoscopy
      for an indication that was considered "generally indicated", it was "generally
      not indicated" for 20%, and it was "not listed" for 16% in the guidelines. The
      diagnostic yield of colonoscopy was highest for the "generally indicated" (38%)
      followed by "not listed" (13%) and "generally not indicated" (5%) categories. In
      the multivariable analysis, the diagnostic yield was independently associated
      with the appropriateness of indication that was "generally indicated" (odds
      ratio=12.3) and referrals by gastroenterologist (odds ratio =1.9). CONCLUSION:
      There is a high likelihood of inappropriate referrals for colonoscopy in an open
      access endoscopy system. The diagnostic yield of the procedure is dependent on
      the appropriateness of indication and referring physician's specialty. Certain
      indications "not listed" in the guidelines have an intermediate diagnostic yield
      and further studies are required to evaluate whether they should be included in
      future revisions of the ASGE guidelines.

PMID- 16437608
TI  - Treatment for isolated loco-regional recurrence of gastric adenocarcinoma: does
      surgery play a role?
AB  - AIM: To evaluate the role of surgical treatment for isolated loco-regional
      recurrences of operated gastric adenocarcinoma. METHODS: Among the 837 patients
      operated for gastric adenocarcinoma between December 1979 and April 2004, 713
      (85%) underwent resection with curative intent. A retrospective review of a
      prospectively collected gastric cancer database was carried out. Overall
      recurrence rate was 44% (315 cases), with 75% occurring within the first 2 years
      from the operation. Isolated L-R recurrences were observed in 38 (12%) patients.
      Symptomatic lesions were observed in 27 (71%). RESULTS: Six (16%) patients were
      macroscopically resected with curative intent. The recurrence was located in the
      gastric stump after a STG in three patients, in the esophagojejunal anastomosis
      after a TG in two patients and in the gastric bed after a TG in one patient.
      Surgical procedures consisted of three secondary TG, two esophagojejunal
      resection and one excision of an extraluminal recurrence. Postoperative
      complications occurred in two patients (33%), including one anastomotic leakage
      and one hemorrhage. The latter patient died of sepsis 35 d after the surgery
      (mortality rate 17%). All patients died of recurrent gastric cancer: 2 within 1
      year from surgery (8 and 11 mo, respectively), 2 after 16 and 17 mo respectively
      and 1 after 28 mo from the second operation. CONCLUSION: Surgery plays a very
      limited role in the treatment for isolated loco-regional recurrence of gastric
      adenocarcinoma.

PMID- 16437610
TI  - Catheter tract implantation metastases associated with percutaneous biliary
      drainage for extrahepatic cholangiocarcinoma.
AB  - AIM: To estimate the incidence of catheter tract implantation metastasis among
      patients undergoing percutaneous transhepatic biliary drainage (PTBD) for
      extrahepatic cholangiocarcinoma, and to provide data regarding the management of
      this unusual complication of PTBD by reviewing cases reported in the literature.
      METHODS: A retrospective analysis of 67 consecutive patients who underwent PTBD
      before the resection of extrahepatic cholangiocarcinoma was conducted. The median
      follow-up period after PTBD was 106 mo. The English language literature (PubMed,
      National Library of Medicine, Bethesda, MD, USA), from January 1966 through
      December 2004, was reviewed. RESULTS: Catheter tract implantation metastasis
      developed in three patients. The cumulative incidence of implantation metastasis
      reached a plateau (6%) at 20 mo after PTBD. All of the three patients with
      implantation metastasis died of tumor progression at 3, 9, and 20 mo after the
      detection of this complication. Among the 10 reported patients with catheter
      tract implantation metastasis from extrahepatic cholangiocarcinoma (including our
      three patients), two survived for more than 5 years after the excision of
      isolated catheter tract metastases. CONCLUSION: Catheter tract implantation
      metastasis is not a rare complication following PTBD for extrahepatic
      cholangiocarcinoma. Although the prognosis for patients with this complication is
      generally poor, the excision of the catheter tract may enable survival in
      selected patients with isolated metastases along the catheter tract.

PMID- 16437609
TI  - Hemoconcentration is a poor predictor of severity in acute pancreatitis.
AB  - AIM: To determine whether the hematocrit (Hct) at admission or at 24 h after
      admission was associated with severe acute pancreatitis (AP), organ failure (OF),
      and pancreatic necrosis. METHODS: A total of 336 consecutive patients with a
      first AP episode were studied. Etiology, Hct values at admission and at 24 h,
      development of severe AP according to Atlanta's criteria, pancreatic necrosis, OF
      and mortality were recorded. Hemoconcentration was defined as Hct level >44% for
      males and >40% for females. The t-test and chi2 test were used to assess the
      association of hemoconcentration to the severity, necrosis and OF. Diagnostic
      accuracy was also determined. RESULTS: Biliary disease was the most frequent
      etiology (n = 148). Mean Hct levels at admission were 41+/-6% for females and
      46+/-7% for males (P<0.01). Seventy-eight (23%) patients had severe AP, and OF
      developed in 45 (13%) patients. According to contrast-enhanced computed
      tomography scan, 36% (54/150) patients showed pancreatic necrosis. Hct levels
      were elevated in 58% (55/96) and 61% (33/54) patients with interstitial and
      necrotizing pancreatitis, respectively. Neither Hct levels at admission nor
      hemoconcentration at 24 h were associated with the severity, necrosis or OF.
      Sensitivity, specificity and positive predictive values for both determinations
      were very low; and negative predictive values were between 61% and 86%, being the
      highest value for OF. CONCLUSION: Hct is not a useful marker to predict a worse
      outcome in acute pancreatitis. In spite of the high negative predictive value of
      hemoconcentration, the prognosis gain is limited due to an already high incidence
      of mild disease.

PMID- 16437611
TI  - Upper gastrointestinal carcinoid tumors incidentally found by endoscopic
      examinations.
AB  - AIM: This study shares Asian clinical experiences of carcinoid tumors that
      originated in the upper gastrointestinal tract. METHODS: From May 1987 to June
      2002, we had found only 13 cases of histologically confirmed carcinoid tumors in
      the upper gastrointestinal tract by endoscopic examinations. There were eight
      males and five females. The mean age was 53.16+/-20.51 years that ranged from 26
      to 82 years. Each of their clinical presentations, locations, tumor morphology,
      and size and the treatment outcome were analyzed and discussed. RESULTS: One
      patient had a polypoid lesion at the lower esophagus, nine were stomach lesions
      and three located at the duodenum. All patients with polypoid and submucosal
      tumor types were of small size (<1.7 cm) and all patients survived after simple
      excision or polypectomy. Four of the five patients in tumor mass forms died and
      the tumors were more than 2.0 cm in size. CONCLUSION: Carcinoid tumors rarely
      originated from the upper gastrointestinal tract and are usually found
      accidentally after endoscopic study. Bigger size (more than 2 cm) tumor masses
      may indicate a more severe disease and poor prognosis.

PMID- 16437612
TI  - Cell cycle and radiosensitivity of progeny of irradiated primary cultured human
      hepatocarcinoma cells.
AB  - AIM: To evaluate the change of growth characteristics and radiosensitivity of
      irradiated primary cultured human hepatocarcinoma cells. METHODS: All tumor
      tissue samples were obtained from 39 hepatocarcinoma patients with a mean age of
      49.6 years (range 22-76 years). We divided the samples into irradiated group and
      non-irradiated group and measured their plating efficiency (PE), population
      doubling time (PDT), radiosensitivity index SF2 and cell cycle. RESULTS: The PDT
      of primary culture of hepatocarcinoma cells was 91.0+/-6.6 h, PE was 12.0+/-1.4%,
      SF2 was 0.41+/-0.05%. The PDT of their irradiated progeny was 124.8+/-5.8 h, PE
      was 5.0+/-0.7%, SF2 was 0.65+/-0.09%. The primary cultured human hepatocarcinoma
      cells showed significant S reduction and G(2) arrest in a dose-dependent manner.
      The progeny of irradiated primary cultured hepatocarcinoma cells grew more slowly
      and its radiosensitivity increased. CONCLUSION: The progeny of irradiated primary
      cultured human hepatocarcinoma cells grows more slowly and its radiosensitivity
      increases.

PMID- 16437613
TI  - Prediction value of radiosensitivity of hepatocarcinoma cells for apoptosis and
      micronucleus assay.
AB  - AIM: To investigate the prediction value of radiosensitivity of hepatocarcinoma
      cells for apoptosis and micronucleus assay. METHODS: Clonogenic assay, flow
      cytometry, and CB micronuclei assay were used to survey the cell survival rate,
      radiation-induced apoptosis and micronucleus frequency of hepatocarcinoma cell
      lines SMMC-7721, HL-7702, and HepG2 after being irradiated by X-ray at the dosage
      ranging 0-8 Gy. RESULTS: After irradiation, there was a dose-effect relationship
      between micronucleus frequency and radiation dosage among the three cell lines
      (P<0.05). A positive relationship was observed between apoptosis and radiation
      dosage among the three cell lines. The HepG2 cells had a significant correlation
      (P<0.05) but apoptosis incidence had a negative relationship with micronucleus
      frequency. There was a positive relationship between apoptosis and radiation
      dosage and the correlation between SMMC-7721 and HL-7702 cell lines had a
      significant difference (P<0.01). After irradiation, a negative relationship
      between cell survival rate and radiation dosages was found among the three cell
      lines (P<0.01). There was a positive relationship between cell survival rate and
      micronucleus frequency (P<0.01). No correlation was observed between apoptosis
      and cell survival rate. CONCLUSION: The radiosensitivity of hepatocarcinoma cells
      can be reflected by apoptosis and micronuclei. Detection of apoptosis and
      micronuclei could enhance the accuracy for predicting radiosensitivity.

PMID- 16437614
TI  - Cell survival curve for primary hepatic carcinoma cells and relationship between
      SF(2) of hepatic carcinoma cells and radiosensitivity.
AB  - AIM: To establish the cell survival curve for primary hepatic carcinoma cells and
      to study the relationship between SF(2) of primary hepatic carcinoma cells and
      radiosensitivity. METHODS: Hepatic carcinoma cells were cultured in vitro using
      39 samples of hepatic carcinoma at stages II-IV. Twenty-nine samples were
      cultured successfully in the fifth generation cells. After these cells were
      radiated with different dosages, the cell survival ratio and SF(2) were
      calculated by clonogenic assay and SF(2) model respectively. The relationship
      between SF(2) and the clinical pathological feature was analyzed. RESULTS: Twenty
      nine of thirty-nine samples were successfully cultured. After X-ray radiation of
      the fifth generation cells with 0, 2, 4, 6, 8 Gy, the cell survival rate was 41%,
      36.5%, 31.0%, 26.8%, and 19%, respectively. There was a negative correlation
      between cell survival and irradiation dosage (r = -0.973, P<0.05). SF(2) ranged
      0.28-0.78 and correlated with the clinical stage and pathological grade of
      hepatic carcinoma (P<0.05). There was a positive correlation between SF(2) and
      D0.5 (r = 0.773, P<0.05). CONCLUSION: SF(2) correlates with the clinical stage
      and pathological grade of hepatic carcinoma and is a marker for predicting the
      radiosensitivity of hepatic carcinomas.

PMID- 16437615
TI  - A case of bowel schistosomiasis not adhering to endoscopic findings.
AB  - Schistosomiasis is a chronic worm infection caused by a species of trematodes,
      the Schistosomes. We may distinguish a urinary form from Schistosomes haematobium
      and an intestinal-hepatosplenic form mainly from Schistosomes mansoni
      characterized by nausea, meteorism, abdominal pain, bloody diarrhea, rectal
      tenesmus, and hepatosplenomegaly. These infections represent a major health issue
      in Africa, Asia, and South America, but recently S mansoni has increased its
      prevalence in other continents, such as Europe countries and North America, due
      to international travelers and immigrants, with several diagnostic and prevention
      problems. We report a case of a 24-year-old patient without HIV infection,
      originated from Ghana, admitted for an afebrile dysenteric syndrome. All
      microbiologic studies were negative and colonoscopy revealed macroscopic lesions
      suggestive of a bowel inflammatory chronic disease. Since symptoms became worse,
      a therapy with mesalazine (2 g/d) was started, depending on the results of a
      bowel biopsy, but without any resolution. The therapy was stopped after 2 wk when
      the following result was available: a diagnosis of ""intestinal schistosomiasis"
      was done (two Schistosoma eggs were detected in the colonic mucosa) and this was
      confirmed by the detection of Schistosoma eggs in the feces. Therapy was
      therefore changed to praziquantel (40 mg/kg, single dose), a specific anti
      parasitic agent, with complete recovery. Schistosomiasis shows some peculiar
      difficulties in terms of differential diagnosis from the bowel inflammatory
      chronic disease, as the two disorders may show similar colonoscopic patterns.
      Since this infection has recently increased its prevalence worldwide, it has to
      be considered in the differential diagnosis of our patients with gastrointestinal
      symptoms.

PMID- 16437616
TI  - Gastric cancer occurring in a patient with Plummer-Vinson syndrome: a case
      report.
AB  - Plummer-Vinson syndrome (sideropenic dysphagia) is characterized by dysphagia due
      to an upper esophageal or hypopharyngeal web in patients with chronic iron
      deficiency anemia. The main cause of dysphagia is the presence of the web in the
      cervical esophagus, and abnormal motility of the pharynx or esophagus is also
      found to play a significant role in this condition. This syndrome is thought to
      be precancerous because squamous cell carcinoma of hypopharynx, oral cavity or
      esophagus takes place in 10% of those patients suffering from this malady, but it
      is even more unusual that Plummer-Vinson syndrome should be accompanied by
      gastric cancer. We have reported here a case of a 43-year-old woman with Plummer
      Vinson syndrome who developed stomach cancer and recovered after a radical total
      gastrectomy with D2 nodal dissection.

PMID- 16437617
TI  - Very high alpha-fetoprotein in a young man due to concomitant presentation of
      hepatocellular carcinoma and Sertoli cell testis tumor.
AB  - Studies reported that there is a close relationship between hepatocellular
      carcinoma (HCC) and testis carcinoma. Both tumors can be presented as synchronal
      tumors, or as testicular metastases of HCC or as hepatic metastases of testicular
      tumor( [7] ). HCC is one of the most common malignancies worldwide and the
      incidence of HCC increases with age( [8] ). The relationship between hepatitis B
      incidence and HCC rates is also well recognized. Alpha fetoprotein (AFP) is
      produced by 70% of HCC. Though a level of AFP >400 ng/mL is diagnostic for HCC,
      in the presence of active hepatitis B infection, the cut-off level should be
      considered to be at least 1 000-4 000 ng/mL. Like HCC, germ cell tumors of the
      testis also release AFP; but it is shown that some of Sertoli cell tumors of
      testis can also release AFP( [10] ). Herein we have reported about the first case
      of HCC in the literature which is presented concomitantly with Sertoli-Leydig
      tumor of testis, leading to extremely high level of AFP in a 21-year-old man.

PMID- 16437618
TI  - Immunosurveillance function of human mast cell?
AB  - Mast cell (MC) is so widely recognized as a critical effector in allergic
      disorders that it can be difficult to think of MC in any other context. Indeed,
      MCs are multifunctional and recently shown that MCs can also act as antigen
      presenters as well as effector elements of human immune system. First
      observations of their possible role as anti-tumor cells in peri- or intra-tumoral
      tissue were mentioned five decades ago and a high content of MCs is considered as
      a favorable prognosis, consistent with this study. Believers of this hypothesis
      assumed them to be inhibitors of tumor development through their pro-apoptotic
      and -necrolytic granules e.g., granzymes and TNF-alpha. However, some still
      postulate them to be enhancers of tumor development through their effects on
      angiogenesis due to mostly tryptase. There are also some data suggesting
      increased MC density causes tumor development and indicates bad prognosis.
      Furthermore, since MC-associated mediators have shown to influence various
      aspects of tumor biology, the net effect of MCs on the development/progression of
      tumors has been difficult to evaluate. For instance, chymase induces apoptosis in
      targets; yet, tryptase, another MC protease, is a well-known mitogen. MCs with
      these various enzyme expression patterns may mediate different functions and the
      predominant MC type in tissues may be determined by the environmental needs. The
      coexistence of tryptase-expressing MCs (MC(T)) and chymase and tryptase
      expressing MCs (MC(TC)) in physiological conditions reflects a naturally
      occurring balance that contributes to tissue homeostasis. We have recently
      discussed the role and relevance of MC serine proteases in different bone marrow
      diseases.

PMID- 16437619
TI  - Hormone receptor status of primary tumor as a prognostic factor in patients with
      liver metastases from breast cancer treated with transcatheter arterial
      chemoembolization.

PMID- 16437621
TI  - Radiation therapy for portal venous invasion by hepatocellular carcinoma.
AB  - AIM: To clarify the efficacy and safety of three-dimensional conformal
      radiotherapy (3-D CRT) for this disease and to specify patient subgroups suitable
      for this treatment. METHODS: Fifty-two patients with HCC received PVI-targeted
      radiation therapy from January 1995 through December 2003. Portal venous invasion
      (PVI) was found in the second or lower order branches of the portal vein in 6
      patients, in the first branch in 24 patients and in the main trunk in 22
      patients. Child classifications of liver function before radiation therapy were
      A, B, and C for 19, 24 and 2 patients, respectively. All patients received three
      dimensional conformal radiotherapy with a total dose ranging from 39 to 60 Gy
      (57.0 Gy in average). RESULTS: Overall survival rates at 1, 2, 3, 4, and 5 years
      were 45.1%, 25.3%, 15.2%, 10.1%, and 5.1%, respectively. Univariate analysis
      revealed that Child status, the number of tumor foci, tumor type, transcatheter
      arterial embolization (TAE) after radiation therapy were statistically
      significant prognostic factors. Multivariate analysis showed that the number of
      tumor foci and TAE after radiation therapy were statistically significant.
      CONCLUSION: The results of this study strongly suggest the efficacy of 3-D CRT as
      treatment for PVI in HCC. 3-D CRT is recommended in combination with post
      radiation TAE for PVI of HCC with 5 tumor foci or less in the liver and with
      Child A liver function.

PMID- 16437620
TI  - Extraintestinal manifestations in inflammatory bowel disease.
AB  - Inflammatory bowel diseases (IBD) can be really considered to be systemic
      diseases since they are often associated with extraintestinal manifestations,
      complications, and other autoimmune disorders. Indeed, physicians who care for
      patients with ulcerative colitis and Crohn's disease, the two major forms of IBD,
      face a new clinical challenge every day, worsened by the very frequent rate of
      extraintestinal complications. The goal of this review is to provide an overview
      and an update on the extraintestinal complications occurring in IBD. Indeed, this
      paper highlights how virtually almost every organ system can be involved,
      principally eyes, skin, joints, kidneys, liver and biliary tracts, and
      vasculature (or vascular system) are the most common sites of systemic IBD and
      their involvement is dependent on different mechanisms.

PMID- 16437622
TI  - Effect of oral Lactococcus lactis containing endostatin on 1, 2-dimethylhydrazine
      induced colon tumor in rats.
AB  - AIM: To investigate the effects of oral Lactococcus lactis (L lactis) containing
      endostatin on 1, 2-dimethylhydrazine (DMH)-induced rat colorectal cancer.
      METHODS: Recombinant endostatin was produced by the expression of L lactis
      NZ9000. Sixty male Wistar rats were injected with DMH (40 mg/kg body weight)
      subcutaneously once a week for 10 wk to induce colorectal cancer. The rats were
      gavaged with 1 mL of endostatin at a dose of 1 x 10(8)/d and fed with the basal
      diet. The animals were killed after 22 wk for histopathological examination. The
      total time of experimental observation was 58 wk. RESULTS: Rat endostatin protein
      was expressed in L lactis. Recombinant endostatin exhibited a significant effect
      on colorectal cancer (P<0.05). Furthermore, the mean survival time of the rats
      treated with endostatin was longer than that of the animals treated with DMH.
      There was no statistically significant difference between the rats treated with
      endostatin and those treated with DMH. The results showed that endostatin could
      not result in complete cure.

PMID- 16437623
TI  - MORT1/FADD is involved in liver regeneration.
AB  - AIM: To explore the role of the adaptor molecule in liver regeneration after
      partial hepatectomy (PH). METHODS: We used transgenic mice expressing an N
      terminal truncated form of MORT1/FADD under the control of the albumin promoter.
      As previously shown, this transgenic protein abrogated CD95- and CD120a-mediated
      apoptosis in the liver. Cyclin A expression was detected using Western blotting.
      ELISA and RT-PCR were used to detect IL-6 and IL-6 mRNA, respectively. DNA
      synthesis in liver tissue was measured by BrdU staining. RESULTS: Resection of
      70% of the liver was followed by a reduced early regenerative response in the
      transgenic group at 36 h. Accordingly, 36 h after hepatectomy, cyclin A
      expression was only detectable in wild-type animals. Consequently, the onset of
      liver mass restoration was retarded as measured by MRI volumetry and mortality
      was significantly higher in the transgenic group. CONCLUSION: Our data
      demonstrate for the first time an involvement of the death receptor molecule
      MORT1/FADD in liver regeneration, beyond its well described role as part of the
      intracellular death signaling pathway.

PMID- 16437624
TI  - Vascular endothelial growth factor and angiopoietins regulate sinusoidal
      regeneration and remodeling after partial hepatectomy in rats.
AB  - AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial
      hepatectomy. METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang
      2, Tie-2, and vascular endothelial growth factor (VEGF) in regenerating liver
      tissue by quantitative reverse-transcription polymerase chain reaction (RT-PCR)
      using a LightCycler (Roche Diagnostics) and also immunohistochemical staining
      after 70% hepatectomy in rats. In the next step, we isolated liver cells
      (hepatocytes, sinusoidal endothelial cell (SEC), Kupffer cell, and hepatic
      stellate cells (HSC)) from regenerating liver tissue by in situ collagenase
      perfusion and counterflow elutriation, to determine potential cellular sources of
      these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs
      were also evaluated by proliferating cell nuclear antigen (PCNA) staining and the
      terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling
      (TUNEL) assay, respectively. RESULTS: VEGF mRNA expression increased with a peak
      at 72 h after hepatectomy, decreasing thereafter. The expression of Ang-1 mRNA
      was present at detectable levels before hepatectomy and increased slowly with a
      peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but
      was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression
      was found mainly in the hepatocyte fraction. Meanwhile, mRNA for Ang-1 and Ang-2
      was found in the SEC and HSC fractions, but was more prominent in the latter. The
      PCNA labeling index of SECs increased slowly, reaching a peak at 72 h, whereas
      apoptotic SECs were detected between 120 h and 144 h. CONCLUSION: Ang-Tie system,
      together with VEGF, plays a critical role in regulating balance between SEC
      proliferation and apoptosis during sinusoidal regeneration after hepatectomy.
      However, the VEGF system plays a more important role in the early phase of
      sinusoidal regeneration than angiopoietin/Tie system.

PMID- 16437625
TI  - Clinical value of rapid urine trypsinogen-2 test strip, urinary trypsinogen
      activation peptide, and serum and urinary activation peptide of carboxypeptidase
      B in acute pancreatitis.
AB  - AIM: To assess the usefulness of urinary trypsinogen-2 test strip, urinary
      trypsinogen activation peptide (TAP), and serum and urine concentrations of the
      activation peptide of carboxypeptidase B (CAPAP) in the diagnosis of acute
      pancreatitis. METHODS: Patients with acute abdominal pain and hospitalized within
      24 h after the onset of symptoms were prospectively studied. Urinary trypsinogen
      2 was considered positive when a clear blue line was observed (detection limit 50
      microg/L). Urinary TAP was measured using a quantitative solid-phase ELISA, and
      serum and urinary CAPAP by a radioimmunoassay method. RESULTS: Acute abdominal
      pain was due to acute pancreatitis in 50 patients and turned out to be
      extrapancreatic in origin in 22 patients. Patients with acute pancreatitis showed
      significantly higher median levels of serum and urinary CAPAP levels, as well as
      amylase and lipase than extrapancreatic controls. Median TAP levels were similar
      in both groups. The urinary trypsinogen-2 test strip was positive in 68% of
      patients with acute pancreatitis and 13.6% in extrapancreatic controls (P<0.01).
      Urinary CAPAP was the most reliable test for the diagnosis of acute pancreatitis
      (sensitivity 66.7%, specificity 95.5%, positive and negative predictive values
      96.6% and 56.7%, respectively), with a 14.6 positive likelihood ratio for a cut
      off value of 2.32 nmol/L. CONCLUSION: In patients with acute abdominal pain,
      hospitalized within 24 h of symptom onset, CAPAP in serum and urine was a
      reliable diagnostic marker of acute pancreatitis. Urinary trypsinogen-2 test
      strip showed a clinical value similar to amylase and lipase. Urinary TAP was not
      a useful screening test for the diagnosis of acute pancreatitis.

PMID- 16437626
TI  - Lymphocytic colitis: a clue to bacterial etiology.
AB  - AIM: To find out the role of bacteria as a possible etiological factor in
      lymphocytic colitis. METHODS: Twenty patients with histopathological diagnosis of
      lymphocytic colitis and 10 normal controls were included in this study.
      Colonoscopic biopsies were obtained from three sites (hepatic and splenic
      flexures and rectosigmoid region). Each biopsy was divided into two parts. A
      fresh part was incubated on special cultures for bacterial growth. The other part
      was used for the preparation of histologic tissue sections that were examined for
      the presence of bacteria with the help of Giemsa stain. RESULTS: Culture of
      tissue biopsies revealed bacterial growth in 18 out of 20 patients with
      lymphocytic colitis mostly Escherichia coli (14/18), which was found in all
      rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic
      flexure specimens respectively. In two of these cases, E coli was associated with
      proteus. Proteus was found only in one case, Klebsiella in two cases, and
      Staphylococcus aureus in one case. In the control group, only 2 out of 10
      controls showed the growth of E coli in their biopsy cultures. Histopathology
      showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with
      positive E coli in their specimen's culture. None of the controls showed these
      bacteria in histopathological sections. CONCLUSION: This preliminary study
      reports an association between E coli and lymphocytic colitis, based on
      histological and culture observations. Serotyping and molecular studies are in
      process to assess the role of E coli in the pathogenesis of lymphocytic colitis.

PMID- 16437627
TI  - Effects of ethanol on antioxidant capacity in isolated rat hepatocytes.
AB  - AIM: To investigate dose-response and time-course of the effects of ethanol on
      the cell viability and antioxidant capacity in isolated rat hepatocytes. METHODS:
      Hepatocytes were isolated from male adult Wistar rats and seeded into 100-mm
      dishes. Hepatocytes were treated with ethanol at concentrations between 0 (C), 10
      (E10), 50 (E50), and 100 (E100) mmol/L (dose response) for 12, 24, and 36 h (time
      course). Then, lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA)
      concentration, glutathione (GSH) level, and activities of glutathione peroxidase
      (GPX), glutathione reductase (GRD), superoxide dismutase (SOD), and catalase
      (CAT) were measured. RESULTS: Our data revealed that LDH leakage was
      significantly increased by about 30% in group E100 over those in groups C and E10
      at 24 and 36 h, The MDA concentration in groups C, E10 and E50 were significantly
      lower than that in group E100 at 36 h. Furthermore, the concentration of MDA in
      group E100 at 36 h was significantly higher by 4.5- and 1.7-fold, respectively,
      than that at 12 and 24 h. On the other hand, the GSH level in group E100 at 24
      and 36 h was significantly decreased, by 32% and 28%, respectively, compared to
      that at 12 h. The activities of GRD and CAT in group E100 at 36 h were
      significantly less than those in groups C and E10. However, The GPX and SOD
      activities showed no significant change in each group. CONCLUSION: These results
      suggest that long-time incubation with higher concentration of ethanol (100
      mmol/L) decreased the cell viability by means of reducing GRD and CAT activities
      and increasing lipid peroxidation.

PMID- 16437629
TI  - Lymphomatous involvement of gastrointestinal tract: evaluation by positron
      emission tomography with (18)F-fluorodeoxyglucose.
AB  - AIM: To demonstrate the (18)F-fluorodeoxyglucose positron emission tomography
      ((18)F-FDG PET) findings in patients with non-Hodgkinos lymphoma (NHL) involving
      the gastrointestinal (GI) tract and the clinical utility of modality despite of
      the known normal uptake of FDG in the GI tract. METHODS: Thirty-three patients
      with biopsy-proven gastrointestinal NHL who had undergone FDG-PET scan were
      included. All the patients were injected with 10-15 mCi FDG and scanned
      approximately 60 min later with a CTI/Siemens HR (+) PET scanner. PET scans were
      reviewed and the maximum standard uptake value (SUV(max)) of the lesions was
      measured before and after the treatment, if data were available and compared with
      histologic diagnoses. RESULTS: Twenty-five patients had a high-grade lymphoma and
      eight had a low-grade lymphoma. The stomach was the most common site of the
      involvement (20 patients). In high-grade lymphoma, PET showed focal nodular or
      diffuse hypermetabolic activity. The average SUV(max)+/-SD was 11.58+/-5.83.
      After the therapy, the patients whose biopsies showed no evidence of lymphoma had
      a lower uptake without focal lesions. The SUV(max)+/-SD decreased from 11.58+/
      5.83 to 2.21+/-0.78. In patients whose post-treatment biopsies showed lymphoma,
      the SUV(max)+/-SD was 9.42+/-6.27. Low-grade follicular lymphomas of the colon
      and stomach showed diffuse hypermetabolic activity in the bowel wall (SUV(max)
      8.2 and 10.3, respectively). The SUV(max) was 2.02-3.8 (mean 3.02) in the stomach
      lesions of patients with MALT lymphoma. ONCLUSION: (18)F-FDG PET contributes to
      the diagnosis of high-grade gastrointestinal non-Hodgkin's lymphoma, even when
      there is the normal background FDG activity. Furthermore, the SUV plays a role in
      evaluating treatment response. Low-grade NHL demonstrates FDG uptake but at a
      lesser intensity than seen in high-grade NHL.

PMID- 16437628
TI  - Bacterial biota in reflux esophagitis and Barrett's esophagus.
AB  - AIM: To identify the bacterial flora in conditions such as Barrettos esophagus
      and reflux esophagitis to determine if they are similar to normal esophageal
      flora. METHODS: Using broad-range 16S rDNA PCR, esophageal biopsies were examined
      from 24 patients [9 with normal esophageal mucosa, 12 with gastroesophageal
      reflux disease (GERD), and 3 with Barrettos esophagus]. Two separate broad-range
      PCR reactions were performed for each patient, and the resulting products were
      cloned. In one patient with Barrettos esophagus, 99 PCR clones were analyzed.
      RESULTS: Two separate clones were recovered from each patient (total = 48),
      representing 24 different species, with 14 species homologous to known bacteria,
      5 homologous to unidentified bacteria, and 5 were not homologous (<97% identity)
      to any known bacterial 16S rDNA sequences. Seventeen species were found in the
      reflux esophagitis patients, 5 in the Barrettos esophagus patients, and 10 in
      normal esophagus patients. Further analysis concentrating on a single biopsy from
      an individual with Barrettos esophagus revealed the presence of 21 distinct
      bacterial species. Members of four phyla were represented, including
      Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Microscopic
      examination of each biopsy demonstrated bacteria in intimate association with the
      distal esophageal epithelium, suggesting that the presence of these bacteria is
      not transitory. CONCLUSION: These findings provide evidence for a complex,
      residential bacterial population in esophageal reflux-related disorders. While
      much of this biota is present in the normal esophagus, more detailed comparisons
      may help identify potential disease associations.

PMID- 16437630
TI  - Have patients with esophagitis got an increased risk of adenocarcinoma? Results
      from a population-based study.
AB  - AIM: To examine an increased risk of esophageal adenocarcinoma is restricted to
      patients who develop Barrett's esophagus or whether esophagitis per se is a risk
      factor for adenocarcinoma. METHODS: A population-based cohort of patients with
      histological evidence of esophagitis without Barrett's esophagus was constructed
      using electronic pathology reports relating to all esophageal biopsies in
      Northern Ireland between 1993 and 1996. Person-years of follow-up and incident
      cases of esophageal cancer were calculated by linking the cohort to death files
      and the Northern Ireland Cancer Registry records. Standardized incidence ratios
      (SIR) were calculated for esophageal cancers (adenocarcinoma, squamous cell
      carcinoma (SCC), and histologically unspecified cancers). RESULTS: A total of 2
      013 patients in the cohort provided 13 559 patient-years of follow-up (mean
      follow-up 6.7 years). None of the patients developed adenocarcinoma. Three
      patients developed SCC, and six developed histologically unspecified cancers. The
      SIR for all esophageal cancers and for SCC were 2.73 (95%CI 1.25-5.19) and 2.93
      (95%CI 0.61-8.59), respectively. In a sensitivity analysis in which all
      unspecified esophageal cancers were treated as adenocarcinomas, the SIR for
      adenocarcinoma was 2.64 (0.97-5.75). CONCLUSION: The risk of adenocarcinoma is
      not elevated in patients with histological evidence of esophagitis without
      Barrett's esophagus; however, these patients may have a moderately increased risk
      of SCC. Further studies are required to confirm these findings, which suggest
      that Barrett's esophagus, not esophagitis, is the key precursor lesion in the
      development of adenocarcinoma.

PMID- 16437631
TI  - Ultrasonographic study of postcibal gastro-esophageal reflux and gastric emptying
      in infants with recurrent respiratory disease.
AB  - AIM: To check the utility of postcibal ultrasonography for the evaluation of
      reflux in relation to gastric emptying in infants with recurrent respiratory
      symptoms and to link imaging with clinical data. METHODS: Esophageal reflux
      (hyperechoic retrograde filling) and gastric emptying (antral areas) were
      quantified before and after ingestion of a standard formula in 35 untreated
      infants (13 with chronic cough, 22 with recurrent bronchitis) and in 31 controls.
      RESULTS: The prevalence of abnormal (> or =8 episodes) postcibal refluxes was 74%
      in patients and 3% in controls. Number, duration of the longest episode and
      extent of refluxes were significantly higher in patients compared to controls.
      Number of refluxes was higher in patients with symptomatic refluxes than in those
      without. Infants with recurrent bronchitis had more refluxes than those with
      chronic cough and controls. Extent and timing of gastric emptying were similar in
      patients and controls. CONCLUSION: Esophageal ultrasonography is a useful and
      physiological test in infants with recurrent respiratory diseases, which have a
      high prevalence of abnormal postcibal esophageal reflux and a gastric emptying
      similar to that of normal controls. Esophageal reflux is more severe in subjects
      with recurrent bronchitis than in those with chronic cough.

PMID- 16437632
TI  - Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous
      clearance of hepatitis C virus infection: a meta-analysis.
AB  - AIM: To assess the associations of human leukocyte antigen (HLA) class II
      DQB1*0301 and/or DRB1*1101 allele with spontaneous hepatitis C virus (HCV)
      clearance by meta-analysis of individual dataset from all studies published till
      date. METHODS: To clarify the impact of HLA class II polymorphisms on viral
      clearance, we performed a meta-analysis of the published data from 11 studies
      comparing the frequencies of DQB1*0301 and DRB1*1101 alleles in individuals with
      spontaneous resolution to those with persistent infection. As we identified the
      heterogeneity between studies, summary statistical data were calculated based on
      a random-effect model. RESULTS: Meta-analyses yielded summary estimates-odds
      ratio (OR) of 2.36 [95%CI (1.62, 3.43), P<0.00001] and 2.02 [95%CI (1.56, 2.62),
      P<0.00001] for the effects of DQB1*0301 and DRB1*1101 alleles on spontaneous
      clearance of HCV, respectively. CONCLUSION: These results support the hypothesis
      that specific HLA class II alleles might influence the susceptibility or
      resistance to persistent HCV infection. Both DQB1*0301 and DRB1*1101 are
      protective alleles and present HCV epitopes more effectively to CD4(+)T
      lymphocytes than others, and subjects with these two alleles are at a lower risk
      of developing chronic HCV infection. Large, multi-ethnic confirmatory and well
      designed studies are needed to determine the host genetic determinants of HCV
      infection.

PMID- 16437633
TI  - Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small
      intestine.
AB  - AIM: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO
      production, attenuates intestinal IR injury. METHODS: Eighteen male rats were
      randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of
      intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC
      treatment before IR. Intestinal microvascular perfusion (IMP) was monitored
      continuously by laser Doppler flowmetry. At the end of the reperfusion, serum
      samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were
      obtained. HO activity in the ileum was assessed at the end of the reperfusion
      period. RESULTS: At the end of the reperfusion in the IR group, IMP recovered
      partially to 42.5% of baseline (P<0.05 vs sham), whereas PDTC improved IMP to
      67.3% of baseline (P<0.01 vs IR). There was a twofold increase in HO activity in
      PDTC group (2 062.66+/-106.11) as compared to IR (842.3+/-85.12) (P<0.001). LDH
      was significantly reduced (P<0.001) in PDTC group (585.6+/-102.4) as compared to
      IR group (1 973.8+/-306.5). Histological examination showed that the ileal mucosa
      was significantly less injured in PDTC group as compared with IR group.
      CONCLUSION: Our study demonstrates that PDTC improves the IMP and attenuates IR
      injury of the intestine possibly via HO production. Additional studies are
      warranted to evaluate the clinical efficacy of PDTC in the prevention of IR
      injury of the small intestine.

PMID- 16437634
TI  - Plasma leptin and ghrelin concentrations in patients with Crohn's disease.
AB  - AIM: To determine the concentrations of leptin and ghrelin, which have opposite
      effects on appetite, energy expenditure, and weight control, in the plasma of
      patients with Crohn's disease (CD), which is often associated with weight loss
      and malnutrition. METHODS: Plasma leptin and ghrelin 'concentrations were
      determined in 28 outpatients with CD by radioimmunoassay. Age- and sex-matched
      controls with and without Helicobacter pylori (H pylori) infection (28 for each)
      were enrolled in the study. Circulating levels of these hormones were assessed
      with respect to CD activity, disease localization and medical treatment. RESULTS:
      There were no significant differences in ghrelin levels between CD patients and H
      pylori-negative controls. However, circulating ghrelin levels were significantly
      lower in H pylori-infected subjects than in CD patients and uninfected controls.
      Plasma leptin levels were comparable among the groups. Localization and
      medication profile had no significant impact on circulating ghrelin and leptin
      levels. CONCLUSION: Apart from H pylori infection, CD itself has no significant
      influence on circulating ghrelin and leptin levels in the outpatients who were
      mostly in inactive state.

PMID- 16437635
TI  - Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in
      chronic hepatitis C.
AB  - AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in
      chronic hepatitis C virus (HCV) infection. METHODS: The model, based on the
      sequential combination of the Bonacini score (BS: ALT/AST ratio, platelet count
      and INR) and ultrasonography liver surface characteristics, was applied to 176
      patients with chronic HCV infection. Assuming a pre-test probability of 35%, the
      model defined four levels of post-test probability of severe fibrosis/cirrhosis:
      <10% (low), 10-74% (not diagnostic), 75-90% (high) and >90% (almost absolute).
      The predicted probabilities were compared with the observed patientso
      distribution according to the histology (METAVIR). RESULTS: Severe
      fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated
      patients in three comparable groups: 34% with a very high (>90%) or low (<10%)
      probability of severe fibrosis, 33% with a probability ranging from 75% to 90%,
      and 33% with an uncertain diagnosis (i.e., a probability ranging from 10% to
      74%). The observed frequency of severe fibrosis/cirrhosis was within the
      predefined ranges. CONCLUSION: The model can correctly identify 67% of patients
      with a high (>75%) or low (<10%) probability of cirrhosis, leaving only 33% of
      the patients still requiring liver biopsy.

PMID- 16437636
TI  - Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of
      developing chronic relapsing pouchitis.
AB  - AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved
      in bacterial recognition and the susceptibility to pouchitis or pouchitis
      severity. METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like
      receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs
      were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients
      who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic
      relapsing pouchitis patients) and 224 Italian Caucasian healthy controls.
      RESULTS: No significant differences were found in SNP frequencies between
      controls and IPAA patients. However, a significant difference in carriership
      frequency of the TLR9-1237C allele was found between the infrequent pouchitis and
      chronic relapsing pouchitis groups [P = 0.028, oddos ratio (OR) = 3.2, 95%CI =
      1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising
      both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced
      combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic
      relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI =
      1.4 -12.3). CONCLUSION: There is no evidence that the SNPs predispose to the need
      for IPAA surgery. The significant increase of the combined carriership of the
      CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group
      suggests that these markers identify a subgroup of IPAA patients with a risk of
      developing chronic or refractory pouchitis.

PMID- 16437637
TI  - Impairment of IFN-alpha production capacity in patients with hepatitis C virus
      and the risk of the development of hepatocellular carcinoma.
AB  - AIM: To determine the utility of interferon (IFN)-alpha production capacity in
      patients with hepatitis C virus (HCV) infection for the measurement of immuno
      surveillance potential and for the early detection of hepatocellular carcinoma
      (HCC) by investigating the Sendai virus (HVJ) stimulated IFN-alpha production
      capacity of patients with HCV infection. METHODS: HVJ stimulated IFN-alpha
      production was determined in a large number of patients with HCV infection and
      the development of HCC was monitored for 3 years in patients with liver cirrhosis
      (LC). RESULTS: IFN-alpha production capacity decreases gradually with the
      progression of liver disease from chronic hepatitis (CH) to HCC. A significant
      correlation between the duration of HCV infection and impaired IFN-alpha
      production capacity was observed. IFN-alpha production in patients who developed
      HCC within 3 years was significantly lower than that of patients who remained in
      LC without developing HCC. CONCLUSION: Measurement of IFN-alpha production in LC
      patients may be useful for the early detection of HCC.

PMID- 16437638
TI  - Risk factors for bleeding after endoscopic mucosal resection.
AB  - AIM: To clarify the risk factors for bleeding after endoscopic mucosal resection
      (EMR). METHODS: A total of 297 consecutive patients who underwent EMR were
      enrolled. Some of the patients had multiple lesions. Bleeding requiring
      endoscopic treatment was defined as bleeding after EMR. Odds ratios (OR) with 95%
      confidence intervals (CI), calculated by logistic regression with multivariate
      adjustments for covariates, were the measures of association. RESULTS: Of the 297
      patients, 57 (19.2%) patients with bleeding after EMR were confirmed. With
      multivariate adjustment, the cutting method of EMR, diameter, and endoscopic
      pattern of the tumor were associated with the risk of bleeding after EMR. The
      multivariate-adjusted OR for bleeding after EMR using endoscopic aspiration
      mucosectomy was 3.07 (95%CI, 1.59-5.92) compared with strip biopsy. The multiple
      adjusted OR for bleeding after EMR for the highest quartile (16-50 mm) of tumor
      diameter was 5.63 (95%CI, 1.84-17.23) compared with that for the lowest (4-7 mm).
      The multiple-adjusted OR for bleeding after EMR for depressed type of tumor was
      4.21 (95%CI, 1.75-10.10) compared with elevated type. CONCLUSION: It is important
      to take tumor characteristics (tumor size and endoscopic pattern) and cutting
      method of EMR into consideration in predicting bleeding after EMR.

PMID- 16437639
TI  - Stool antigen tests in the diagnosis of Helicobacter pylori infection before and
      after eradication therapy.
AB  - AIM: To evaluate two enzyme immunoassay-based stool antigen tests, Premier
      Platinum HpSA and Amplified IDEIA HpStAR, and one rapid test, ImmunoCard STAT!
      HpSA, in the primary diagnosis of Helicobacter pylori (H pylori) infection and
      after eradication therapy. METHODS: Altogether 1 574 adult subjects were screened
      with a whole-blood H pylori antibody test and positive results were confirmed
      with locally validated serology and (13)C-urea breath test. All 185 subjects,
      confirmed to be H pylori positive, and 97 H pylori-negative individuals, randomly
      selected from the screened study population and with negative results in serology
      and UBT, were enrolled. After eradication therapy the results of 182 subjects
      were assessed. RESULTS: At baseline, the sensitivity of HpSA and HpStAR was 91.9%
      and 96.2%, respectively, and specificity was 95.9% for both tests. ImmunoCard had
      sensitivity of 93.0% but specificity of only 88.7%. After eradication therapy,
      HpSA and HpStAR had sensitivity of 81.3% and 100%, and specificity of 97.0% and
      97.6%, respectively. ImmunoCard had sensitivity of 93.8% and specificity of
      97.0%. HpSA, HpStAR, and ImmunoCard had PPV 77%, 80%, and 75%, and NPV 98%, 100%,
      and 99%, respectively. CONCLUSION: In primary diagnosis, the EIA-based tests
      performed well. After eradication therapy, negative results were highly accurate
      for all the three tests. HpStAR had the best overall performance.

PMID- 16437640
TI  - Disrupted NF- kappa B activation after partial hepatectomy does not impair
      hepatocyte proliferation in rats.
AB  - AIM: To analyze the effects of NF- kappa B inhibition by antioxidant pyrrolidine
      dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver
      regeneration after partial hepatectomy (PH). METHODS: Saline, PDTC or PTX were
      injected 1 h before PH and rats were killed at 0.5 and 24 h after PH. Several
      control groups were used for comparison (injection control groups). RESULTS:
      Compared to saline injected controls, NF- kappa B activation was absent 0.5 h
      after PH in rats treated with PDTC or PTX. At 24 h after PH, DNA synthesis and
      PCNA expression were identical in treated and control rats and thus occurred
      irrespectively of the status of NF- kappa B activation at 0.5 h. Signal
      transducer and activator of transcription 3 (Stat3) activation was observed
      already 0.5 h after PH in saline, PDTC or PTX group and was similar to Stat3
      activation in response to injection without PH. CONCLUSION: These data strongly
      suggest that (1) NF- kappa B p65/p50 DNA binding produced in response to PH is
      not a signal necessary to initiate the liver regeneration, (2) Stat3 activation
      is a stress response unrelated to the activation of NF- kappa B. In conclusion,
      NF- kappa B activation is not critically required for the process of liver
      regeneration after PH.

PMID- 16437642
TI  - Effects of fermented soy milk on the liver lipids under oxidative stress.
AB  - AIM: To investigate the effects of fermented soy milk powder on the antioxidative
      status and lipid metabolism in the livers of CCl4-injected rats. METHODS: Forty
      five healthy male Sprague-Dawley rats were randomly assigned to five groups
      according to five different diets: control (AIN-76), AIN-76+high-dose fermented
      soy milk powder, AIN-76+low-dose fermented soy milk powder, AIN-76+high-dose milk
      yogurt powder and AIN-76+low-dose milk yogurt powder. The experiment lasted for 8
      wk. After 4 wk, all the rats received intraperitoneal administration of
      CCl(4)(0.2 mL/100 g body weight) every week. Total cholesterol (TC), triglyceride
      (TG), TBARS, ALP, and antioxidative enzymes in the liver were evaluated. RESULTS:
      There was also no significant difference in TBARS and antioxidative enzymes in
      the liver. TC and TG in the groups fed with fermented soy milk powder were
      generally lower than those fed with casein powder. CONCLUSION: Consumption of
      fermented soy milk was positive in lowering total cholesterol and TG accumulation
      in the liver under CCl(4)-induced oxidative stress.

PMID- 16437641
TI  - Serum arylesterase and paraoxonase activity in patients with chronic hepatitis.
AB  - AIM: To investigate the relationship between serum paraoxonase (PON1), AST, ALT,
      GGT, and arylesterase (AE) activity alterations and the degree of liver damage in
      patients with chronic hepatitis. METHODS: We studied 34 chronic hepatitis
      patients and 32 control subjects, aged between 35 and 65 years, in the Department
      of Infection and Clinical Microbiology at the Firat University School of
      Medicine. Blood samples were collected from subjects between 8:00 and 10:00 a.m.
      following a 12-h fast. Baseline and salt-stimulated PON1 activities were measured
      by the hydrolysis of paraoxon. Phenyl acetate was used as the substrate and
      formed phenol was measured spectrophotometrically at 270 nm after the addition of
      a 10-fold diluted serum sample in AE activity measurements. RESULTS: The results
      of this investigation revealed that the levels of AE activity decreased from
      132+/-52 to 94+/-36 (29%), baseline PON1 activity from 452+/-112 to 164+/-67
      (64%), salt-stimulated PON1 activity from 746+/-394 to 294+/-220 (61%), HDL from
      58.4+/-5.1 to 47.2+/-5.6 (20%), triglyceride from 133+/-51.2 to 86+/-34.0 (35%),
      while a slight increase in the level of LDL (from 163+/-54.1 to 177.3+/-56.0; 9%)
      and significant increases in the levels of AST (from 29+/-9.3 to 98+/-44), ALP
      (from 57.2+/-13.1 to 91+/-38.1), ALT (from 27.9+/-3.32 to 89+/-19.1), GGT (from
      24.3+/-2.10 to 94+/-48.2), total bilirubin (from 0.74+/-0.02 to 1.36+/-0.06; 84%)
      and direct bilirubin (from 0.18+/-0.01 to 0.42+/-0.04; 133%) were detected.
      However, the levels of albumin, total protein, cholesterol, and uric acid were
      almost the same in chronic hepatitis and the control subjects. CONCLUSION: Low
      PON1 and AE activity may contribute to the increased liver dysfunction in chronic
      hepatitis patients by reducing the ability of HDL to retard LDL oxidation and
      might be clinically useful for monitoring the disease of chronic hepatitis.

PMID- 16437643
TI  - Alteration of chaperonin60 and pancreatic enzyme in pancreatic acinar cell under
      pathological condition.
AB  - AIM: To investigate the changes of chaperonin60 (Cpn60) and pancreatic enzymes in
      pancreatic acinar cells, and to explore their roles in the development of
      experimental diabetes and acute pancreatitis (AP). METHODS: Two different
      pathological models were replicated in Sprague-Dawley rats: streptozotocin
      induced diabetes and sodium deoxycholate-induced AP. The contents of Cpn60 and
      pancreatic enzymes in different compartments of the acinar cells were measured by
      quantitative immunocytochemistry. RESULTS: The levels of Cpn60 significantly
      increased in diabetes, but decreased in AP, especially in the zymogen granules of
      the pancreatic acinar cells. The elevation of Cpn60 was accompanied with the
      increased levels of pancreatic lipase and chymotrypsinogen in diabetes. However,
      a decreased Cpn60 level was accompanied by high levels of lipase and
      chymotrypsinogen in AP. The amylase level was markedly reduced in both the
      pathological conditions. CONCLUSION: The equilibrium between Cpn60 and pancreatic
      enzymes in the acinar cells breaks in AP, and Cpn60 content decreases, suggesting
      an insufficient chaperone capacity. This may promote the aggregation and
      autoactivation of the premature enzymes in the pancreatic acinar cells and play
      roles in the development of AP.

PMID- 16437644
TI  - Determination of platelet-activating factor by reverse phase high-performance
      liquid chromatography and its application in viral hepatitis.
AB  - AIM: To detect the platelet-activating factor (PAF) and the plasma or serum
      levels of tumor necrosis factor-alpha (TNF-alpha) malondialdehyde (MDA),
      endotoxin (ET) and to discuss their significance in various types of viral
      hepatitis. METHODS: PAF, TNF-alpha, MDA, and ET levels in 60 controls, 16 cases
      of acute viral hepatitis, 71 cases of chronic viral hepatitis, 19 cases of severe
      viral hepatitis were detected by reverse phase high-performance liquid
      chromatography (rHPLC), bio-assay, ELISA, thiobarbituric acid (TBA), and limulus
      lysate test (LLT), respectively. RESULTS: The rHPLC was more sensitive and
      specific than bio-assay (r = 0.912, P<0.01). The plasma levels of PAF, TNF-alpha,
      MDA, and ET in patients with viral hepatitis were higher than those in controls
      (P<0.01). CONCLUSION: rHPLC is more reliable and accurate for the detection of
      PAF.

PMID- 16437645
TI  - Chloromycetin resistance of clinically isolated E coli is conversed by using EGS
      technique to repress the chloromycetin acetyl transferase.
AB  - AIM: To explore the possibility of repression of chloromycetin (Cm) acyl
      transferase by using external guided sequence (EGS) in order to converse the
      clinical E coli isolates from Cm- resistant to Cm- sensitive. METHODS: EGS
      directed against chloromycetin acetyl transferase gene (cat) was cloned to vector
      pEGFP-C1 which contains the kanamycin (Km) resistance gene. The recombinant
      plasmid pEGFP-C1+EGScat1+cat2 was constructed and the blank vector without EGS
      fragment was used as control plasmids. By using the CaCl(2) transformation
      method, the recombinant plasmids were introduced into the clinically isolated Cm
      resistant but Km sensitive E coli strains. Transformants were screened on LB agar
      plates containing Km. Extraction of plasmids and PCR were applied to identify the
      positive clones. The growth curve of EGS transformed bacteria cultured in broth
      with Cm resistance was determined by using spectrophotometer at A(600). Drug
      sensitivity was tested in solid culture containing Cm by using KB method.
      RESULTS: Transformation studies were carried out on 16 clinically isolated Cm
      resistant (250 microg/mL of Cm) E coli strains by using pEGFP-C1-EGScat1cat2
      recombinant plasmid. Transformants were screened on LB-agar plates containing Km
      after the transformation using EGS. Of the 16 tested strains, 4 strains were
      transformed successfully. Transformants with EGS plasmid showed growth inhibition
      when grown in liquid broth culture containing 200 microg/mL of Cm. In drug
      sensitivity test, these strains were sensitive to Cm on LB-agar plates containing
      200 microg/mL of Cm. Extraction of plasmids and PCR amplification showed the
      existence of EGS plasmids in these four transformed strains. These results
      indicated that the Cat of the four clinical isolates had been suppressed and the
      four strains were converted to Cm sensitive ones. CONCLUSION: The EGS directed
      against Cat is able to inhibit the expression of Cat, and hence convert Cm
      resistant bacteria to Cm-sensitive ones. Thus, the EGS has the capability of
      converting the phenotype of clinical drug-resistant isolates strains to drug
      sensitive ones.

PMID- 16437646
TI  - Peritoneal lavage cytology and carcinoembryonic antigen determination in
      predicting peritoneal metastasis and prognosis of gastric cancer.
AB  - AIM: To evaluate the role of peritoneal lavage cytology (PLC) and
      carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in
      predicting the peritoneal metastasis and prognosis after curative resection of
      gastric cancer. METHODS: PLC and radioimmunoassay of CEA were performed in
      peritoneal washes from 64 patients with gastric cancer and 8 patients with benign
      diseases. RESULTS: The positive rate of pCEA (40.6%) was significantly higher
      than that of PLC (23.4%) (P<0.05). The positive rates of PLC and pCEA correlated
      with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was
      found to have a higher sensitivity and a lower false-positive rate in predicting
      peritoneal metastasis after curative resection of gastric cancer as compared to
      PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic
      findings or positive pCEA results were significantly lower than those of patients
      with negative cytologic findings or negative pCEA results (P<0.05). Multivariate
      analysis indicated that pCEA was an independent prognostic factor for the
      survival of patients with gastric cancer. CONCLUSION: Intraoperative pCEA is a
      more sensitive and reliable predictor of peritoneal metastasis as well as
      prognosis in patients with gastric cancer as compared to PLC method.

PMID- 16437647
TI  - Small intestinal submucosa improves islet survival and function during in vitro
      culture.
AB  - AIM: To evaluate the recovery and function of isolated rat pancreatic islets
      during in vitro culture with small intestinal submucosa (SIS). METHODS:
      Pancreatic islets were isolated from Wistar rats by standard surgical procurement
      followed by intraductal collagenase distension, mechanical dissociation and
      Euroficoll purification. Purified islets were cultured in plates coated with
      multilayer SIS (SIS-treated group) or without multilayer SIS (standard cultured
      group) for 7 and 14 d in standard islet culture media of RPMI 1640. After
      isolation and culture, islets from both experimental groups were stained with
      dithizone and counted. Recovery of islets was determined by the ratio of counts
      after the culture to the yield of islets immediately following islet isolation.
      Viability of islets after the culture was assessed by the glucose challenge test
      with low (2.7 mmol/L) and high glucose (16.7 mmol/L) solution supplemented with
      50 mmol/L 3-isobutyl-1-methylxanthine (IBMX) solution. Apoptosis of islet cells
      after the culture was measured by relative quantification of histone-complexed
      DNA fragments using ELISA. RESULTS: After 7 or 14 d of in vitro tissue culture,
      the recovery of islets in SIS-treated group was significantly higher than that
      cultured in plates without SIS coating. The recovery of islets in SIS-treated
      group was about twice more than that of in the control group. In SIS-treated
      group, there was no significant difference in the recovery of islets between
      short- and long-term periods of culture (95.8+/-1.0% vs 90.8+/-1.5%, P>0.05).
      When incubated with high glucose (16.7 mmol/L) solution, insulin secretion in SIS
      treated group showed a higher increase than that in control group after 14 d of
      culture (20.7+/-1.1 mU/L vs 11.8+/-1.1 mU/L, P<0.05). When islets were placed in
      high glucose solution containing IBMX, stimulated insulin secretion was higher in
      SIS-treated group than in control group. Calculated stimulation index of SIS
      treated group was about 23 times of control group. In addition, the stimulation
      index of SIS-treated group remained constant regardless of short- and long-term
      periods of culture (9.5+/-0.2 vs 10.2+/-1.2, P>0.05). Much less apoptosis of
      islet cells occurred in SIS-treated group than in control group after the
      culture. CONCLUSION: Co-culture of isolated rat islets with native sheet-like SIS
      might build an extracellular matrix for islets and provide possible biotrophic
      and growth factors that promote the recovery and subsequent function of islets.

PMID- 16437648
TI  - Complete or partial trisomy 3 in gastro-intestinal MALT lymphomas co-occurs with
      aberrations at 18q21 and correlates with advanced disease stage: a study on 25
      cases.

PMID- 16437649
TI  - Helicobacter pylori-infected animal models are extremely suitable for the
      investigation of gastric carcinogenesis.
AB  - Although various animal models have been developed to clarify gastric
      carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent
      years. Since the recognition of the pathogenicity of Helicobacter pylori (H
      pylori), several animal models with H pylori infection have been developed to
      confirm the association between H pylori and gastric cancer. Nonhuman primate and
      rodent models were suitable for this study. Japanese monkey model revealed
      atrophic gastritis and p53 mutation after long-term infection of H pylori.
      Mongolian gerbil model showed the development of gastric carcinoma with H pylori
      infection alone, as well as with combination of chemical carcinogens, such as N
      methyl-N-nitrosourea and N-methyl-N-nitro-N'-nitrosoguanidine. The
      histopathological changes of these animal models after H pylori inoculation are
      closely similar to those in human beings with H pylori infection. Eradication
      therapy attenuated the development of gastric cancer in H pylori-infected
      Mongolian gerbil. Although several features of animal models differ from those
      seen in human beings, these experimental models provide a starting point for
      further studies to clarify the mechanism of gastric carcinogenesis as a result of
      H pylori infection and assist the planning of eradication therapy to prevent
      gastric carcinoma.

PMID- 16437651
TI  - Vitamin B12 deficiency and gastric histopathology in older patients.
AB  - AIM: To compare upper gastric endoscopic and histopathologic findings in older
      adults in the presence and absence of B12 deficiency. METHODS: A prospective
      analysis of upper gastric endoscopic and gastric histopathologic findings from 30
      newly identified B12-deficient patients (11 males, 19 females) and 16 controls
      with normal B12 status (6 males, 10 females) was performed. For all subjects, the
      indication for upper endoscopy and gastric biopsy were unrelated to B12 status. A
      single pathologist, blinded to B12 status, processed and interpreted the biopsy
      samples. Endoscopic and histopathologic findings were correlated with age,
      gender, hematocrit (Hct), MCV and B12 status. RESULTS: The B12-deficient group
      had significantly lower mean serum B12 levels compared to the controls
      (P<0.00005) while their mean Hct, MCV and serum albumin levels were similar. Iron
      deficiency (ferritin-based) was present in 21% of B12-deficient patients and
      intrinsic factor antibodies were present in 29% (5/17) of B12-deficient patients.
      The endoscopic findings revealed significantly different rates of gastritis and
      atrophy between the B12-deficient and control groups (P=0.017). B12-deficient
      patients had significantly less superficial gastritis (62% vs 94%) and
      significantly more atrophic gastritis (28% vs 0%) as compared to the controls
      (P=0.039). Intestinal metaplasia was similar in both groups. Helicobacter pylori
      infection rates were similar in the B12-deficient patients and controls (40% vs
      31%). CONCLUSION: Significantly different endoscopic findings and types of
      gastritis could often be observed in the presence and absence of B12 deficiency.
      Atrophy, based on endoscopy, and atrophic gastritis, based on histopathology,
      suggest the presence of B12 deficiency. Gastric histopathology is not influenced
      by the age, gender, Hct or MCV of the patients.

PMID- 16437650
TI  - Effect of p27(KIP1) on cell cycle and apoptosis in gastric cancer cells.
AB  - AIM: To elucidate the effect of p27(KIP1) on cell cycle and apoptosis regulation
      in gastric carcinoma cells. METHODS: The whole length of p27(KIP1) cDNA was
      transfected into human gastric cancer cell line SCG7901 by lipofectamine.
      Expression of p27(KIP1) protein or mRNA was analyzed by Western blot and RNA dot
      blotting, respectively. Effect of p27(KIP1) on cell growth was observed by MTT
      assay and anchorage-independent growth in soft agar. Tumorigenicity in nude mice
      was used to assess the in vivo biological effect of p27(KIP1). Flow cytometry,
      TUNEL, and electron microscopy were used to assess the effect of p27(KIP1) on
      cell cycle and apoptosis. RESULTS: Expression of p27(KIP1) protein or mRNA
      increased evidently in SCG7901 cells transfected with p27(KIP1). The cell growth
      was reduced by 31% at 48 h after induction with zinc determined by cell viability
      assay. The alteration of cell malignant phenotype was evidently indicated by the
      loss of anchorage-independent growth ability in soft agar. The tumorigenicity in
      nude mice was reduced evidently (0.55+/-0.14 cm vs 1.36+/-0.13 cm, P<0.01).
      p27(KIP1) overexpression caused cell arrest with 36% increase (from 33.7% to
      69.3%, P<0.01) in G1 population. Prolonged p27(KIP1) expression induced apoptotic
      cell death reflected by pre-G1 peak in the histogram of FACS, which was also
      confirmed by TUNEL assay and electron microscopy. CONCLUSION: p27(KIP1) can
      prolong cell cycle in G1 phase and lead to apoptosis. p27(KIP1) may be a good
      candidate for cancer gene therapy.

PMID- 16437652
TI  - Reperfusion injury after critical intestinal ischemia and its correction with
      perfluorochemical emulsion "perftoran".
AB  - AIM: To investigate the anti-ischemic properties of perfluorochemical emulsion
      "perftoran" in mesenteric region. METHODS: Experiments were conducted on 146
      nonlinear white male rats weighing 200-350 g. Partial critical intestinal
      ischemia was induced by thorough atraumatic strangulation of 5-6 cm jejunal loop
      with its mesentery for 90 min. Global critical intestinal ischemia was made by
      atraumatic occlusion of the cranial mesenteric artery (CMA) for 90 min also.
      Perftoran (PF, 0.8-1.0 mL per 100 g) in experimental groups or 0.9% sodium
      chloride in control groups was injected at 75 min of ischemic period. Mean
      systemic arterial blood pressure (BP(M)) registration, intravital microscopy and
      morphological examination of ischemic intestine and its mesentery were performed
      in both groups. RESULTS: During 90 min of reperfusion, BP(M) progressively
      decreased to 27.3+/-7.4% after PF administration vs 38.6+/-8.0% in the control
      group of rats with partial intestinal ischemia (NS) and to 50.3+/-6.9% vs 53.1+/
      5.8% in rats after global ischemia (NS). During the reperfusion period, full
      restoration of microcirculation was never registered; parts with restored blood
      flow had leukocyte and erythrocyte stasis and intra-vascular clotting, a typical
      "non-reflow" phenomenon. The reduction of mesenteric 50-400 mum feeding artery
      diameter was significantly less in the PF group than in the control group (24+/
      5.5% vs 45.2+/-3.6%, P<0.05) 5 min after partial intestinal ischemia. This
      decrease progressed but differences between groups minimized at the 90(th) min of
      reperfusion (41.5+/-4.2% and 50.3+/-2.8%, respectively). In reperfusion of rat's
      intestine, a significant mucosal alteration was registered. Villous height
      decreased 2.5-3 times and the quantity of crypts decreased more than twice. In
      the group of rats administered PF, intestinal mucosal layer was protected from
      irreversible post-ischemic derangement during reperfusion. Saved cryptal
      epithelial cells were the source of regeneration of the epithelium, which began
      to cover renewing intestinal villi after 24 h of blood flow restoration. View of
      morphological alterations was more heterogeneous in CMA groups. CONCLUSION:
      Systemic administration of perftoran promotes earlier and more complete
      structural regeneration during reperfusion in rats after partial and global
      critical intestinal ischemia.

PMID- 16437653
TI  - Effects of arginine supplementation on splenocyte cytokine mRNA expression in
      rats with gut-derived sepsis.
AB  - AIM: To investigate the effects of arginine (Arg)-enriched diets before sepsis
      and/or Arg-containing total parenteral nutrition (TPN) after sepsis or both on
      cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis.
      METHODS: Rats were assigned to four experimental groups. Groups 1 and 2 were fed
      with a semipurified diet, while groups 3 and 4 had part of the casein replaced by
      Arg which provided 2% of the total calories. After the rats were fed with these
      diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), at the
      same time an internal jugular vein was cannulated. All rats were maintained on
      TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2
      and 4 were supplemented with Arg which provided 2% of the total calories in the
      TPN solution. All rats were killed 3 d after CLP to examine their splenocyte
      subpopulation distribution and cytokine expression levels. RESULTS: Plasma
      interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha) and interferon
      (IFN-gamma) were not detectable 3 d after CLP. There were no differences in the
      distributions of CD45Ra(+), CD3(+), CD4(+), and CD8(+) cells in whole blood and
      splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg
      supplemented groups was significantly higher than that in group 1. IL-4 mRNA
      expression in groups 3 and 4 was significantly higher than that in groups 1 and
      2. The mRNA expression of IL-10 and IFN-gamma was significantly higher in group 4
      than in the other three groups. There was no difference in TNF-alpha mRNA
      expression among the four groups. CONCLUSION: The influence of Arg on the whole
      blood and splenic lymphocyte subpopulation distribution is not obvious. However,
      Arg administration, especially before and after CLP, significantly enhances the
      mRNA expression levels of Th1 and Th2 cytokines in the spleen of rats with gut
      derived sepsis.

PMID- 16437655
TI  - A novel gain of function mutant in C-kit gene and its tumorigenesis in nude mice.
AB  - AIM: To transfect mutant C-kit cDNA at codon 579 into human embryonic kidney cell
      line to observe its role in the pathogenesis of gastrointestinal stromal tumor
      (GIST). METHODS: Eukaryotic expression vectors of pcDNA3-Kit-NW and pcDNA3-Kit-W
      were constructed. Then pcDNA3-Kit-NW and pcDNA3-Kit-W plasmids were transfected
      into human embryonic kidney cell line by Lipofectamine. The resistant clone was
      screened by G418 filtration and identified by sequencing, Western blotting, and
      immunocytochemical staining. Human embryonic kidney cells were divided into three
      groups including pcDNA3-Kit-NW, pcDNA3-Kit-W, and vector control groups.
      Absorbency value with a wavelength of 574 nm was detected by MTT analysis. Mice
      were injected with three groups of cells. Volume, mass, and histological
      examinations of the tumors in different groups were measured and compared.
      RESULTS: The C-kit gene and mutant C-kit gene were successfully cloned into the
      eukaryotic expression vector pcDNA3. pcDNA3-Kit-NW and pcDNA3-Kit-W were
      successfully transfected into human embryonic kidney cell line and showed stable
      expression in this cell line. Cell proliferating activity had significant
      differences between pcDNA3-Kit-NW and pcDNA3, pcDNA3-Kit-NW and pcDNA3-Kit-W
      (P<0.05), respectively. Tumors were only observed in nude mice implanted with
      cells transfected with pcDNA3-Kit-NW. CONCLUSION: Mutation of C-kit gene
      increases the proliferation activity of human cells and plays an important role
      in the malignant transformation of GIST.

PMID- 16437654
TI  - Secretory expression and characterization of a recombinant-deleted variant of
      human hepatocyte growth factor in Pichia pastoris.
AB  - AIM: To study the secretory expression of human hepatocyte growth factor (hdHGF)
      gene in Pichia pastoris. METHODS: The full-length gene of human cDNA encoding the
      deleted variant of hdHGF was cloned by RT-PCR and overlapping-fragment PCR
      technique using mRNA of human placenta as a template. The cloned hdHGF cDNA was
      inserted into the Escherichia coli-yeast shuttle vector of pPIC9. The constructed
      plasmid, pPIC9-hdHGF, was transformed into the GS115 cells of the methylotrophic
      yeast, P pastoris, using a chemical method. The Mut(+ ) transformants were
      screened to obtain high-expression strains by the test and analysis of expressed
      products of shake-flask culture. A secretory form of rhdHGF was made with the aid
      of the leader peptide sequence of Saccharomyces cerevisiae alpha-factor. RESULTS:
      The expressed products, which showed a band of molecular mass of about 80 ku,
      were observed on 15% SDS-PAGE and identified by Western blotting and N-terminal
      amino acid sequencing. In the high cell density culture of 5 L fermentor by fed
      batch culture protocol, the cell biomass was reached at approximately 135 g
      (DCW)/L. The productivity of secreted total supernant protein concentration
      attained a high-level expression of more than 8.0 g/L and the ratio of rhdHGF
      band area was about 12.3% of the total band area scanned by SDS-PAGE analysis,
      which estimated that the product of rhdHGF was 500-900 mg/L. CONCLUSION: The P
      pastoris system represents an attractive tool of generating large quantities of
      hdHGF for both research and industrial purposes.

PMID- 16437656
TI  - Associations between gamma-glutamyl transferase, metabolic abnormalities and
      inflammation in healthy subjects from a population-based cohort: a possible
      implication for oxidative stress.
AB  - AIM: To examine the relationships between gamma-glutamyl-transferase (GGT),
      alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and various
      metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker
      (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a
      population-based sample. METHODS: Two hundred and five subjects with normal body
      mass index (BMI), glucose tolerance, and without any metabolic abnormality were
      studied out of 1 339 subjects, without known liver diseases, alcohol abuse or use
      of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti
      (north-western Italy). RESULTS: In all patients metabolic parameters and hs-CRP
      levels linearly increase from the lowest to the highest ALT and GGT tertiles,
      while in subjects without metabolic abnormalities, there is a significant
      association between fasting glucose, uric acid, waist circumference, hs-CRP,
      triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP
      and glucose levels are associated with GGT levels in a multiple regression model,
      after adjustments for multiple confounders. In the same model, median NT levels
      are significantly associated with the increasing GGT tertile (beta = 1.06; 95%CI
      0.67-1.45), but not with the AST and ALT tertiles. In a multiple regression
      model, after adjusting for age, sex, BMI, waist, smoking, and alcohol
      consumption, both NT (beta = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (beta =
      0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.
      CONCLUSION: GGT, an easy, universally standardized and available measurement,
      could represent an early marker of sub-clinical inflammation and oxidative stress
      in otherwise healthy individuals. Prospective studies are needed to establish if
      GGT could predict future diabetes in these subjects.

PMID- 16437657
TI  - Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in
      maintaining remission in pediatric Crohn's disease: a double-blind, randomized,
      placebo-controlled study.
AB  - AIM: To assess the value of long-chain omega-3 fatty acids (FAs) supplementation
      in addition to amino-salicylic-acid (5-ASA) in pediatric patients with Crohn's
      disease (CD). METHODS: Thirty-eight patients (20 males and 18 females, mean age
      10.13 years, range 5-16 years) with CD in remission were randomized into two
      groups and treated for 12 mo. Group I (18 patients) received 5-ASA (50 mg/kg/d)+
      omega-3 FAs as triglycerides in gastro-resistant capsules, 3 g/d (eicosapentanoic
      acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g). Group II (20 patients)
      received 5-ASA (50 mg/kg/d)+olive oil placebo capsules. Patients were evaluated
      for fatty acid incorporation in red blood cell membranes by gas chromatography at
      baseline 6 and 12 mo after the treatment. RESULTS: The number of patients who
      relapsed at 1 year was significantly lower in group I than in group II (P<0.001).
      Patients in group I had a significant increase in the incorporation of EPA and
      DHA (P<0.001) and a decrease in the presence of arachidonic acids. CONCLUSION:
      Enteric-coated omega-3 FAs in addition to treatment with 5-ASA are effective in
      maintaining remission of pediatric CD.

PMID- 16437658
TI  - Outcome of non-variceal acute upper gastrointestinal bleeding in relation to the
      time of endoscopy and the experience of the endoscopist: a two-year survey.
AB  - AIM: To prospectively assess the impact of time of endoscopy and endoscopist's
      experience on the outcome of non-variceal acute upper gastrointestinal (GI)
      bleeding patients in a large teaching hospital. METHODS: All patients admitted
      for non-variceal acute upper GI bleeding for over a 2-year period were
      potentially eligible for this study. They were managed by a team of seven
      endoscopists on 24-h call whose experience was categorized into two levels (high
      and low) according to the number of endoscopic hemostatic procedures undertaken
      before the study. Endoscopic treatment was standardized according to Forrest
      classification of lesions as well as the subsequent medical therapy. Time of
      endoscopy was subdivided into two time periods: routine (8 a.m.-5 p.m.) and on
      call (5 p.m.-8 a.m.). For each category of experience and time periods rebleeding
      rate, transfusion requirement, need for surgery, length of hospital stay and
      mortality we compared. Multivariate analysis was used to discriminate the impact
      of different variables on the outcomes that were considered. RESULTS: Study
      population consisted of 272 patients (mean age 67.3 years) with endoscopic
      stigmata of hemorrhage. The patients were equally distributed among the
      endoscopists, whereas only 19% of procedures were done out of working hours.
      Rockall score and Forrest classification at admission did not differ between time
      periods and degree of experience. Univariate analysis showed that higher
      endoscopist's experience was associated with significant reduction in rebleeding
      rate (14% vs 37%), transfusion requirements (1.8+/-0.6 vs 3.0+/-1.7 units) as
      well as surgery (4% vs 10%), but not associated with the length of hospital stay
      nor mortality. By contrast, outcomes did not significantly differ between the two
      time periods of endoscopy. On multivariate analysis, endoscopist's experience was
      independently associated with rebleeding rate and transfusion requirements. Odds
      ratios for low experienced endoscopist were 4.47 for rebleeding and 6.90 for need
      of transfusion after the endoscopy. CONCLUSION: Endoscopist's experience is an
      important independent prognostic factor for non-variceal acute upper GI bleeding.
      Urgent endoscopy should be undertaken preferentially by a skilled endoscopist as
      less expert staff tends to underestimate some risk lesions with a negative
      influence on hemostasis.

PMID- 16437660
TI  - Upregulation of 25-hydroxyvitamin D(3)-1(alpha)-hydroxylase by butyrate in Caco-2
      cells.
AB  - AIM: To investigate the possible involvement of 25-hydroxyvitamin D(3)-1(alpha)
      hydroxylase [1alpha-25(OH) (2) D(3)] in butyrate-induced differentiation in human
      intestinal cell line Caco-2 cells. METHODS: Caco-2 cells were incubated either
      with 3 mmol/L butyrate and 1 micromol/L 25(OH) (2) D(3) or with 1 micromol/L
      1alpha-25(OH) (2) D(3) for various time intervals ranging from 0 to 72 h.
      Additionally, cells were co-incubated with butyrate and either 25(OH) (2) D(3) or
      1alpha-25(OH) (2) D(3). 1alpha-25(OH) (2) D(3) mRNA was determined semi
      quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for
      the detection of 1alpha-25(OH) (2) D(3) protein. Finally, enzymatic activity was
      measured by ELISA. RESULTS: Both butyrate and 1alpha-25(OH) (2) D(3) stimulated
      differentiation of Caco-2 cells after a 48 h incubation period, while 25(OH) (2)
      D(3) had no impact on cell differentiation. Synergistic effects on
      differentiation were observed when cells were co-incubated with butyrate and
      vitamin D metabolite. Butyrate transiently upregulated 1alpha-25(OH) (2) D(3)
      mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic
      activity was enhanced significantly. The induction of the enzyme allowed for
      comparable differentiating effects of both vitamin D metabolites. CONCLUSION: Our
      experimental data provide a further mechanism for the involvement of the vitamin
      D signaling pathway in colonic epithelial cell differentiation by butyrate. The
      enhancement of 1alpha-25(OH) (2) D(3) followed by antiproliferative effects of
      the vitamin D prohormone in the Caco-2 cell line suggest that 25(OH) (2) D(3) in
      combination with butyrate may offer a new therapeutic approach for the treatment
      of colon cancer.

PMID- 16437659
TI  - Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects
      who had undergone surgery for gastric adenocarcinoma in Northwest Italy.
AB  - AIM: To investigate the seroprevalence of Helicobacter pylori (H pylori)
      infection and its more virulent strains as well as the correlation with the
      histologic features among patients who had undergone surgery for gastric cancer
      (GC). METHODS: Samples from 317 (184 males, 133 females, mean age 69+/-3.4 years)
      consecutive patients who had undergone surgery for gastric non-cardia
      adenocarcinoma were included in the study. Five hundred and fifty-five (294
      males, 261 females, mean age 57.3+/-4.1 years) patients consecutively admitted to
      the Emergency Care Unit served as control. Histological examination of tumor,
      lymph nodes and other tissues obtained at the time of surgery represented the
      diagnostic "gold standard". An enzyme immunosorbent assay was used to detect
      serum anti-H pylori (IgG) antibodies and Western blotting technique was utilized
      to search for anti-CagA protein (IgG). RESULTS: Two hundred and sixty-one of
      three hundred and seventeen (82.3%) GC patients and 314/555 (56.5%) controls were
      seropositive for anti-H pylori (P<0.0001; OR, 3.58; 95%CI, 2.53-5.07). Out of the
      317 cases, 267 (84.2%) were seropositive for anti-CagA antibody vs 100 out of 555
      (18%) controls (P<0.0001; OR, 24.30; 95%CI, 16.5-35.9). There was no difference
      between the frequency of H pylori in intestinal type carcinoma (76.2%) and
      diffuse type cancer (78.8%). Intestinal metaplasia (IM) was more frequent but not
      significant in the intestinal type cancer (83.4% vs 75.2% in diffuse type and
      72.5% in mixed type). Among the patients examined for IM, 39.8% had IM type I,
      8.3% type II and 51.9% type III(type III vs others, P = 0.4). CONCLUSION: This
      study confirms a high seroprevalence of H pylori infection in patients suffering
      from gastric adenocarcinoma and provides further evidence that searching for CagA
      status over H pylori infection might confer additional benefit in identifying
      populations at greater risk for this tumor.

PMID- 16437661
TI  - Using the polymerase chain reaction coupled with denaturing gradient gel
      electrophoresis to investigate the association between bacterial translocation
      and systemic inflammatory response syndrome in predicted acute severe
      pancreatitis.
AB  - AIM: To investigate the use of PCR and DGGE to investigate the association
      between bacterial translocation and systemic inflammatory response syndrome in
      predicted severe AP. METHODS: Patients with biochemical and clinical evidence of
      acute pancreatitis and an APACHE II score > or = 8 were enrolled. PCR and DGGE
      were employed to detect bacterial translocation in blood samples collected on d
      1, 3, and 8 after the admission. Standard microbial blood cultures were taken
      when there was clinical evidence of sepsis or when felt to be clinically
      indicated by the supervising team. RESULTS: Six patients were included. Of all
      the patients investigated, only one developed septic complications; the others
      had uneventful illness. Bacteria were detected using PCR in 4 of the 17 collected
      blood samples. The patient with sepsis was PCR-positive in two samples (taken on
      d 1 and 3), despite three negative blood cultures. Using DGGE and specific
      primers, the bacteria in all blood specimens which tested positive for the
      presence of bacterial DNA were identified as E coli. CONCLUSION: Our study
      confirmed that unlike traditional microbiological techniques, PCR can detect the
      presence of bacteria in the blood of patients with severe AP. Therefore, this
      latter method in conjunction with DGGE is potentially an extremely useful tool in
      predicting septic morbidity and evaluating patients with the disease. Further
      research using increased numbers of patients, in particular those patients with
      necrosis and sepsis, is required to assess the reliability of PCR and DGGE in the
      rapid diagnosis of infection in AP.

PMID- 16437662
TI  - Gastro esophageal reflux disease is associated with absence from work: results
      from a prospective cohort study.
AB  - AIM: To study the association of gastro-esophageal reflux disease (GERD) with the
      absence from work and to estimate the extent of loss in gross domestic product
      due to inability to work. METHODS: Analysis was based on the prospectively
      gathered data of a large European cohort study involving 6 215 symptomatic GERD
      patients (ProGERD). Among these patients, 2 871 were initially employed. The
      calculation of the loss of gross domestic product was based on the assumption
      that the prevalence of GERD was about 15% in Germany. According to the German
      Federal Statistical Office, the mean gross wage of employees was 150 EUR/d in
      2002. RESULTS: The data of 2 078 employed patients who were prospectively
      followed up for over 2 years were analyzed. At study entry, the patients reported
      a mean of 1.8 d per year of inability to work. During the prospective follow-up
      under routine clinical care, the proportion of patients reporting days with
      inability to work decreased from 14% to 6% and the mean number of days per year
      with inability to work decreased to 0.9 d. Assuming a prevalence of troublesome
      GERD of 15% in the employed German population, the loss of gross domestic product
      amounted to 668 million EUR/year in Germany. CONCLUSION: GERD causes a relevant
      impairment on the national economics by absence from work. The presented data
      demonstrate the importance of GERD, not only for patients and health insurance
      companies, but also for the community at large.

PMID- 16437663
TI  - Internet-based data inclusion in a population-based European collaborative follow
      up study of inflammatory bowel disease patients: description of methods used and
      analysis of factors influencing response rates.
AB  - AIM: To describe an Internet-based data acquisition facility for a European 10
      year clinical follow-up study project of a population-based cohort of
      inflammatory bowel disease (IBD) patients and to investigate the influence of
      demographic and disease related patient characteristics on response rates.
      METHODS: Thirteen years ago, the European Collaborative study group of IBD (EC
      IBD) initiated a population-based prospective inception cohort of 2 201 uniformly
      diagnosed IBD patients within 20 well-described geographical areas in 11 European
      countries and Israel. For the 10-year follow-up of this cohort, an electronic
      patient questionnaire (ePQ) and electronic physician per patient follow-up form
      (ePpPFU) were designed as two separate data collecting instruments and made
      available through an Internet-based website. Independent demographic and clinical
      determinants of ePQ participation were analyzed using multivariate logistic
      regression. RESULTS: In 958 (316 CD and 642 UC) out of a total number of 1 505
      (64%) available IBD patients, originating from 13 participating centers from nine
      different countries, both ePQ and ePpPFU were completed. Patients older than 40
      years at ePQ completion (OR: 1.53 (95%CI: 1.14-2.05)) and those with active
      disease during the 3 mo previous to ePQ completion (OR: 3.32 (95%CI: 1.57-7.03))
      were significantly more likely to respond. CONCLUSION: An Internet-based data
      acquisition tool appeared successful in sustaining a unique Western-European and
      Israelian multi-center 10-year clinical follow-up study project in patients
      afflicted with IBD.

PMID- 16437664
TI  - Serum insulin, insulin resistance, beta-cell dysfunction, and gallstone disease
      among type 2 diabetics in Chinese population: a community-based study in Kinmen,
      Taiwan.
AB  - AIM: To explore the association of serum insulin, insulin resistance, and beta
      cell dysfunction with gallstone disease (GSD) in type 2 diabetics. METHODS: We
      used a community-based study conducted between 1991 and 1993 in Kinmen, Taiwan to
      identify type 2 diabetics. A screening program for GSD was performed in 2001 by a
      panel of specialists who employed real-time ultrasound sonography to examine the
      abdominal region after the patient had fasted for at least 8 h. Screening was
      conducted in 2001 on 848 patients diagnosed with type 2 diabetes. The HOMA method
      was used to compare the profile differences for insulin resistance (HOMA IR) and
      beta-cell dysfunction (HOMA beta-cell). RESULTS: We studied 440 type 2 diabetics
      who attended sonography check-ups. After excluding eight insulin-treated
      diabetics, the prevalence of GSD among the remaining 432 was 13.9% (26/187) among
      males and 14.7% (36/245) among females. After adjustment for other GSD-associated
      risk factors in addition to age and obesity, GSD risk increased among females
      with levels of serum insulin [4(th) vs 1(st) quartile odds ratios (OR) = 4.46
      (95%CI: 1.71-11.66)] and HOMA IR [4(th) vs 1(st) quartile OR = 4.46 (95%CI: 1.71
      11.66)]. Better HOMA beta-cell function was significantly related to decreased
      risk of GSD [4(th) vs 1(st) quartile OR = 0.16 (95%CI: 0.03-1.70)]. Among males,
      age and central obesity were the most significant risk factors for GSD. No
      association of GSD with serum insulin, HOMA IR, and HOMA beta-cell was observed
      among males. CONCLUSION: Serum insulin, insulin resistance, and beta-cell
      dysfunction are risk factors for GSD in females, but not males with type 2
      diabetes.

PMID- 16437665
TI  - Evaluation of immunogenicity and reactogenicity of recombinant DNA hepatitis B
      vaccine produced in India.
AB  - AIM: (1) To gain information on immune responses to an accelerated schedule of 0,
      1, and 2 mo in paramedical staff and BDS students who are at an increased risk of
      getting hepatitis B infection and come under high risk groups. (2) To assess the
      efficacy and safety of Enivac-HB in different age groups, using genetically
      modified yeast strain Pichia pastoris, a new recombinant hepatitis B vaccine
      developed and manufactured in India. METHODS: A prospective, comparative, and
      single blinded trial of rapid (0, 1, and 2 mo) hepatitis B immunization schedule
      was reported. A total of three hundred and seven (212 females and 95 males)
      healthy volunteers divided into three age groups (18-29, 30-39, and 40-49) were
      enrolled after screening for markers of hepatitis B. All the volunteers received
      20 mg of the vaccine intramuscularly at 0, 1, and 2 mo. RESULTS: Geometric mean
      titers were calculated pre and post vaccination. Before immunization the GMT was
      0.0124 mIU/mL. One month after the administration of the third dose of
      recombinant vaccine 296/307 (96.5%) subjects achieved seroprotective levels of
      anti-HBs. The geometric mean anti-HBs titers achieved after one month of the
      third dose was 2 560.0 mIU/mL. The geometric mean anti-HBs titer of males was 2
      029.0 mIU/mL, while that of the females was 2 759.0 mIU/mL. In the age group of
      18-29 years, anti-HBs titer was 3 025.0 mIU/mL, while that in the age group of 30
      39 years was 2 096.0 mIU/mL. In third age group of 40-49 years, anti-HBs titer
      was 1 592.0 mIU/mL. Hyper-responses (anti-HBs> or =100 mIU/mL) were shown in
      88.0% (271/307) of subjects. Eleven (3.5%) subjects responded poorly to the
      vaccine in the age group of 40-49 years. There was only mild pain at the site of
      injection otherwise there were no other adverse drug reactions (ADRs).
      CONCLUSION: This vaccine (Enivac-HB) is safe and efficacious, providing
      significant protection after the third dose and rapid hepatitis B immunization
      schedule of 0, 1, and 2 mo can be recommended whenever rapid protection is the
      goal.

PMID- 16437666
TI  - Bone disorders in experimentally induced liver disease in growing rats.
AB  - AIM: To investigate the change of bone parameters in a new model of
      experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in
      growing rats. METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride
      (CCl(4)), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection
      were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral
      length, cortical index (quotient of cortical thickness and whole diameter) and
      ultimate bending load (F(max)) of the femora were determined. The results in
      animals treated with DEN+PB+CCl(4) (DPC, n = 21) were compared to those in
      untreated animals (UNT, n = 14) and in control group treated only with DEN+PB
      (DP, n = 20). RESULTS: Fatty liver and cirrhosis developed in each DPC-treated
      rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in
      this group at wk 8, but each parameter was lower (P<0.05 for each) at wk 16 in
      comparison to the control group. Neither fatty liver nor cirrhosis was observed
      in DP-treated animals at any time point. Femoral length and F(max) values were
      higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT
      controls. However, no difference was found at wk 16. CONCLUSION: Experimental
      liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced
      bone mass, and decreased mechanical resistance in growing rats. Our results are
      in concordance with the data of other studies using different animal models. A
      novel finding is the transiently accelerated skeletal growth and bone strength
      after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.

PMID- 16437667
TI  - Retinol-binding protein, acute phase reactants and Helicobacter pylori infection
      in patients with gastric adenocarcinoma.
AB  - AIM: To determine the serum levels of c-reactive protein (CRP), transferrin
      (TRF), a2-macroglobulin (A2M), ceruloplasmin (CER), a1-acid glycoprotein (AAG),
      pre-albumin (P-ALB) and retinol-binding protein (RBP) in gastric carcinoma
      patients and to explore their possible correlation with underlying Helicobacter
      pylori (H pylori) infection. METHODS: We measured the serum levels of CRP, TRF,
      A2M, CER, AAG, P-ALB, and RBP in 153 preoperative patients (93 males; mean age:
      63.1+/-11.3 years) with non-cardia gastric adenocarcinoma and 19 healthy
      subjects. RESULTS: The levels of CRP, CER, RBP, and AAG in cancer patients were
      significantly higher than those in healthy controls (P<0.0001), while no
      difference was found regarding the TRF, P-ALB, and A2M levels. Cancer patients
      with H pylori infection had significantly lower RBP values compared to non
      infected ones (P<0.0001) and also higher values of CRP and AAG (P = 0.09 and P =
      0.08, respectively). CONCLUSION: High serum levels of CRP, CER and AAG in cancer
      patients do not seem to be related to H pylori infection. Retinol-binding protein
      seems to discriminate between infected and non-infected patients with gastric
      carcinoma. Further studies are needed to explore if it is directly involved in
      the pathogenesis of the disease or is merely an epiphenomenon.

PMID- 16437668
TI  - Histological outcome of chronic hepatitis B in children treated with interferon
      alpha.
AB  - AIM: To evaluate the effect of interferon alpha (IFN-alpha) treatment on the
      liver histology in children with chronic hepatitis B and to evaluate the
      usefulness of various histological scoring systems of liver histology in this
      group of patients. METHODS: Fibrosis stage and inflammation grade were assessed
      according to Batts and Ludwig, Ishak et al., and METAVIR (only fibrosis stage)
      before and 12 mo after IFN-alpha treatment termination in 93 children aged 2-16
      years with chronic hepatitis B. RESULTS: None of the three numerical scoring
      systems for liver fibrosis showed statistically significant differences in liver
      fibrosis, while evolution of inflammatory activity revealed statistically
      significant improvement in the whole group of children with chronic hepatitis B
      treated with IFN-alpha and in responders. Significantly positive correlations
      were found between fibrosis stage and inflammation grade in the respective
      scoring systems. CONCLUSION: Treatment with IFN-alpha did not improve
      histological fibrosis but decreased inflammatory activity in children with
      chronic hepatitis B. The three semiquantitative scoring systems seem to be
      comparable in the estimation of the inflammation grade and fibrosis stage in this
      group of children.

PMID- 16437669
TI  - Effects of Helicobacter pylori infection on gastric epithelial cell kinetics in
      patients with chronic renal failure.
AB  - AIM: To evaluate the effects of Helicobacter pylori infection on gastric
      epithelial cell kinetics in patients with chronic renal failure (CRF). METHODS:
      Forty-four patients were enrolled in this study and divided into four groups with
      respect to their Helicobacter pylori (H pylori) and CRF status. Groups were
      labeled as follows: 1a: normal renal function, H pylori negative (n = 12), 1b:
      normal renal function, H pylori positive (n = 11), 2a: CRF, H pylori negative (n
      = 10), 2b: CRF, H pylori positive (n = 11). Upper gastrointestinal endoscopy was
      done in all the patients involved in the study. During endoscopical
      investigation, antral biopsy specimens were taken from each patient. In order to
      evaluate the cell apoptosis and proliferation in gastric epithelial cells, Bax
      and proliferating cell nuclear antigen (PCNA) labeling indexes (LI) were assessed
      with immunohistochemical staining method. RESULTS: For groups 1a, 1b, 2a, and 2b,
      mean Bax LI was identified as 34.4+/-13.7, 44.1+/-16.5, 46.3+/-20.5, 60.7+/-13.8,
      respectively and mean PCNA LI was identified as 36.2+/-17.2, 53.6+/-25.6, 59.5+/
      25.6, 67.2+/-22, respectively. When the one-way ANOVA test was applied,
      statistically significant differences were detected between the groups for both
      Bax LI (P = 0.004 <0.01) and PCNA LI (P = 0.009 <0.01). When groups were compared
      further in terms of Bax LI and PCNA LI with Tukeyos HSD test for multiple
      pairwise comparisons, statistically significant difference was observed only
      between groups 1a and 2b (P = 0.006 <0.01). CONCLUSION: In gastric epithelial
      cells, expression of both the pre-apoptotic protein Bax and the proliferation
      marker PCNA increase with H pylori infection. This increase is more evident in
      patients with uremia. These findings suggest that uremia accelerates apoptosis
      and proliferation in gastric epithelial cells.

PMID- 16437670
TI  - Intrahepatic and peripheral T-cell responses in genotype 1b hepatitis C virus
      infected patients with persistently normal and elevated aminotransferase levels.
AB  - AIM: To evaluate whether the cytokine responses in liver and serum differ in
      chronic hepatitis C patients with normal and high alanine aminotransferase (ALT)
      levels. METHODS: Thirty-three (16 with normal ALT level as group 1 and 17 with
      elevated ALT level as group 2) patients infected with genotype 1b hepatitis C
      virus (HCV) were examined. Liver infiltrating lymphomononuclear cells (LILMCs)
      were isolated from liver biopsy by collagenase type 1 and stimulated with
      phytohemagglutinin and interleukin 2 (IL-2). IL-10, IL-12, interferon gamma (IFN
      gamma) and tumor necrosis factor alpha (TNF-alpha) were determined in serum and
      LILMCs by ELISA. RESULTS: Serum cytokine levels were similar in both groups
      (P>0.05). Stimulated IFN-gamma and TNF-alpha levels in LILMCs were increased in
      both groups. IL-12 and IL-10 levels stimulated with IL-2 were higher in group 1
      than in group 2 (P = 0.023). Histological activity index (HAI) and stage had a
      negative correlation with TNF-alpha and IFN-gamma levels in group 2. CONCLUSION:
      Increased T-helper type 2 (Th2) cytokine response may regress inflammatory and
      biochemical activity. Progression of histological abnormalities in persons with
      elevated ALT probably depends on insufficient Th2 cytokine response, which does
      not balance Th1 cytokine response.

PMID- 16437671
TI  - Diagnostic accuracy of serum biochemical fibrosis markers in children with
      chronic hepatitis B evaluated by receiver operating characteristics analysis.
AB  - AIM: To investigate the diagnostic accuracy of potent serum biochemical fibrosis
      markers in children with chronic hepatitis B evaluated by receiver operating
      characteristics (ROC) analysis. METHODS: We determined the serum level of
      apolipoprotein A-I (APO A-I), haptoglobin (HPT) and a-2 macroglobulin (A2M) with
      an automatic nephelometer in 63 children (age range 4-17 years, mean 10 years)
      with biopsy-verified chronic HBeAg-positive hepatitis B. Fibrosis stage and
      inflammation grade were assessed in a blinded fashion according to Batts and
      Ludwig. We defined mild liver fibrosis as a score < or =2 and advanced fibrosis
      as a score equal to 3. ROC analysis was used to calculate the power of the assays
      to detect advanced liver fibrosis (AccuROC, Canada). RESULTS: Serum
      concentrations of APO A-I, HPT and A2M were not significantly different in
      patients with chronic hepatitis B compared to controls. However, APO A-I level of
      1.19 ng/L had a sensitivity of 85.7% and a specificity of 60.7% (AUC = 0.7117, P
      = 0.035) to predict advanced fibrosis. All other serum biochemical markers and
      their combination did not allow a useful prediction. None of these markers was a
      good predictor of histologic inflammation. CONCLUSION: Apolipoprotein A-I may be
      a suitable serum marker to predict advanced liver fibrosis in children with
      chronic hepatitis B.

PMID- 16437672
TI  - Effects of L-carnitine in patients with hepatic encephalopathy.
AB  - AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia
      effects on patients with hepatic encephalopathy (HE). METHODS: One hundred and
      fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B
      infection, 78 patients with hepatitis C virus infection, 21 patients with
      cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into
      group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into
      group B receiving placebo in double blind. RESULTS: At the end of the study
      period, a significant decrease in NH4 fasting serum levels was found in patients
      with hepatic encephalopathy (P<0.05) after the treatment with levocarnitine (LC).
      Significant differences were also found between symbol digit modalities test and
      block design in patients with hepatic encephalopathy (P<0.05). CONCLUSION:
      Results of our study suggest an important protective effect of L-carnitine
      against ammonia-precipitated encephalopathy in cirrhotic patients.

PMID- 16437673
TI  - Synergistic action of famotidine and chlorpheniramine on acetic acid-induced
      chronic gastric ulcer in rats.
AB  - AIM: To assess the synergistic action of famotidine (FMD) and chlorpheniramine
      (CPA) on acetic acid-induced chronic gastric ulcer in rats. METHODS: Chronic
      gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal
      application of the acetic acid. Forty SD rats were randomly divided into blank
      group (n = 8), control group (n = 8), FMD group (n = 8), CPA group (n = 8), and
      FMD+CPA group (n = 8). Each group was given intraperitoneally (i.p.) 0.5 mL/100 g
      distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10 mg/kg CPA, 4 mg/kg FMD+10
      mg/kg CPA, respectively, daily for 10 d. On d 10, ulcer area was determined by
      planimetry. The level of myeloperoxidase (MPO) in the liver homogenization was
      determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1
      alpha (6-keto-PGF(1a)) and IL-8 were determined by radioimmunoassay. RESULTS: The
      synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF(1a) and MPO
      were confirmed. The effect of FMD+CPA group was significantly different as
      compared to the control and FMD groups. The lesion (mm(2)) was reduced from
      40.18+/-2.6 in control group to 6.83+/-2.97 in PMD+CPA group, P<0.01, and from
      32.9+/-3.27 in FMD group to 6.83+/-2.97 in PMD+CPA group, P<0.01. The plasma
      levels of IL-8 decreased from 0.69+/-0.11 ng/L in control group to 0.4+/-0.04
      ng/L in PMD+CPA group, P<0.01, and from 0.51+/-0.08 ng/L in FMD group to 0.4+/
      0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF(1a) increased from
      7.55+/-1.65 ng/L in control group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.01,
      and from 13.15+/-1.48 ng/L in FMD group to 16.62+/-0.97 ng/L in PMD+CPA group,
      P<0.05. The levels of MPO in the liver homogenate decreased from 9.12+/-2.05 u/L
      in control group to 4.33+/-0.95 u/L in PMD+CPA group, P<0.01, and from 8.3+/-1.29
      u/L in FMD group to 4.33+/-0.95 u/L, P<0.01. CONCLUSION: The synergistic action
      of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the
      incidence of ulcer and also enhances the healing of ulcer.

PMID- 16437674
TI  - Effect of liniment levamisole on cellular immune functions of patients with
      chronic hepatitis B.
AB  - AIM: To explore the effects of liniment levamisole on cellular immune functions
      of patients with chronic hepatitis B. METHODS: The levels of T lymphocyte subsets
      and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin
      streptavidin (BSA) technique in patients with chronic hepatitis B before and
      after the treatment with liniment levamisole. RESULTS: After one course of
      treatment with liniment levamisole, the levels of CD3(+), CD4(+), and the ratio
      of CD4(+)/CD8(+) increased as compared to those before the treatment but the
      level of CD8(+) decreased. The total expression level of mIL-2R in PBMCs
      increased before and after the treatment with liniment levamisole. CONCLUSION:
      Liniment levamisole may reinforce cellular immune functions of patients with
      chronic hepatitis B.

PMID- 16437675
TI  - Correlation between the expressions of gastrin, somatostatin and cyclin and
      cyclin-depend kinase in colorectal cancer.
AB  - AIM: To explore the correlation between the expressions of gastrin (GAS),
      somatostatin (SS) and cyclin, cyclin-dependent kinase (CDK) in colorectal cancer,
      and to detect the specific regulatory sites where gastrointestinal hormone
      regulates cell proliferation. METHODS: Seventy-nine resected large intestine
      carcinomatous specimens were randomly selected. Immunohistochemical staining for
      GAS, SS, cyclin D1, cyclin E, cyclin A, cyclin B1, CDK2 and CDK4 was performed
      according to the standard streptavidin-biotin-peroxidase (S-P) method. According
      to the semi-quantitative integral evaluation, SS and GAS were divided into high,
      middle and low groups. Cyclin D1, cyclin E, cyclin A, cyclin B1, CDK2, CDK4
      expressions in the three GAS and SS groups were assessed. RESULTS: The positive
      expression rate of cyclin D1 was significantly higher in high (78.6%, 11/14) and
      middle GAS groups (73.9%, 17/23) than in low GAS group (45.2%, 19/42) (P<0.05,
      c2(high vs low) = 4.691; P<0.05, c2(middle vs low) = 4.945). The positive
      expression rate of cyclin A was significantly higher in high (100%, 14/14) and
      middle GAS groups (82.6%, 19/23) than in low GAS group (54.8%, 23/42) (P<0.01,
      c2(high vs low) = 9.586; P<0.05, c2(middle vs low) = 5.040). The positive
      expression rate of CDK2 was significantly higher in high (92.9%, 13/14) and
      middle GAS groups (87.0%, 20/23) than in low GAS group (50.0%, 21/42) (P<0.01,
      c2(high vs low) = 8.086; P<0.01, c2(middle vs low) = 8.715). The positive
      expression rate of CDK4 was significantly higher in high (78.6%, 11/14) and
      middle GAS groups (78.3%, 18/23) than in low GAS group (42.9%, 18/42) (P<0.05,
      c2(high vs low) = 5.364; P<0.01, c2(middle vs low) = 7.539). The positive
      expression rate of cyclin E was prominently higher in low SS group (53.3%, 24/45)
      than in high (9.1%, 1/11) and middle (21.7%, 5/23) SS groups (P<0.05, c2(high vs
      low) = 5.325; P<0.05, c2(middle vs low) = 6.212). The positive expression rate of
      CDK2 was significantly higher in low SS group (77.8%, 35/45) than in high SS
      group (27.3%, 3/11) (P<0.01, c2(high vs low) = 8.151). There was a significant
      positive correlation between the integral ratio of GAS to SS and the semi
      quantitative integral of cyclin D1, cyclin E, cyclin A, CDK2, CDK4 (P<0.05,
      (D1)r(s) = 0.252; P<0.01, (E)r(s) = 0.387; P<0.01, (A)r(s) = 0.466; P<0.01,
      (K2)r(s) = 0.519; P<0.01, (K4)r(s) = 0.434). CONCLUSION: The regulation and
      control of gastrin, SS in colorectal cancer cell growth may be directly related
      to the abnormal expressions of cyclins D1, A, E, and CDK2, CDK4. The regulatory
      site of GAS in the cell cycle of colorectal carcinoma may be at the G(1), S and
      G(2) phases. The regulatory site of SS may be at the entrance of S phase.

PMID- 16437676
TI  - Delayed development of hepatocellular carcinoma during long-term follow-up after
      eradication of hepatitis C virus by interferon therapy.
AB  - A 42-year-old Japanese man with liver cirrhosis by hepatitis C virus (HCV) had
      successful interferon therapy in May 1991. Since then, serum HCV-RNA and liver
      function tests had been negative. He had continued to drink more than 100 g/d of
      alcohol as before. In June 2003, a 5-cm tumor was found in the posterior segment
      of the liver. The tumor was curatively resected and the surgical specimen showed
      a well-differentiated hepatocellular carcinoma (HCC). Non-cancerous lesions of
      the liver revealed fibrosis at stage F3 with minimal to mild inflammation of
      grade A1. Heavy drinking may retard the dissolution of fibrosis and accelerate
      HCC development in patients with sustained virological response.

PMID- 16437677
TI  - Effect of pseudolaric acid B on gastric cancer cells: inhibition of proliferation
      and induction of apoptosis.
AB  - AIM: To examine the effect of pseudolaric acid B on the growth of human gastric
      cancer cell line, AGS, and its possible mechanism of action. METHODS: Growth
      inhibition by pseudolaric acid B was analyzed using MTT assay. Apoptotic cells
      were detected using Hoechst 33258 staining, and confirmed by DNA fragmentation
      analysis. Western blot was used to detect the expression of apoptosis-regulated
      gene Bcl-2, caspase 3, and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1).
      RESULTS: Pseudolaric acid B inhibited the growth of AGS cells in a time- and dose
      dependent manner by arresting the cells at G(2)/M phase, which was accompanied
      with a decrease in the levels of cdc2. AGS cells treated with pseudolaric acid B
      showed typical characteristics of apoptosis including chromatin condensation and
      DNA fragmentation. Moreover, treatment of AGS cells with pseudolaric acid B was
      also associated with decreased levels of the anti-apoptotic protein Bcl-2,
      activation of caspase-3, and proteolytic cleavage of PARP-1. CONCLUSION:
      Pseudolaric acid B can dramatically suppress the AGS cell growth by inducing
      apoptosis after G(2)/M phase arrest. These findings are consistent with the
      possibility that G(2)/M phase arrest is mediated by the down-regulation of cdc2
      levels. The data also suggest that pseudolaric acid B can trigger apoptosis by
      decreasing Bcl-2 levels and activating caspase-3 protease.

PMID- 16437678
TI  - Effects of six months losartan administration on liver fibrosis in chronic
      hepatitis C patients: a pilot study.
AB  - AIM: To evaluate the safety and efficacy of chronic administration of losartan on
      hepatic fibrosis in chronic hepatitis C patients. METHODS: Fourteen patients with
      chronic hepatitis C non-responders (n = 10), with contraindications (n = 2) or
      lack of compliance (n = 2) to interferon plus ribavirin therapy and liver
      fibrosis were enrolled. Liver and renal function test, clinical evaluation, and
      liver biopsies were performed at baseline and after losartan administration at a
      dose of 50 mg/d during the 6 mo. The control group composed of nine patients with
      the same inclusion criteria and paired liver biopsies (interval 6-14 mo).
      Histological activity index (HAI) with fibrosis stage was assessed under blind
      conditions by means of Ishak's score. Subendothelial fibrosis was evaluated by
      digital image analyses. RESULTS: The changes in the fibrosis stage were
      significantly different between losartan group (decrease of 0.5+/-1.3) and
      controls (increase of 0.89+/-1.27; P<0.03). In the treated patients, a decrease
      in fibrosis stage was observed in 7/14 patients vs 1/9 control patients (P<0.04).
      A decrease in sub-endothelial fibrosis was observed in the losartan group. No
      differences were found in HAI after losartan administration. Acute and chronic
      decreases in systolic arterial pressures (P<0.05) were observed after the
      losartan administration, without changes in mean arterial pressure or renal
      function. CONCLUSION: Chronic AT-II type 1 receptor (AT1R) blockade may reduce
      liver fibrosis in patients with chronic hepatitis C.

PMID- 16437679
TI  - Tumor necrosis factor-alpha-induced protein 1 and immunity to hepatitis B virus.
AB  - AIM: To compare the gene expression profile in a pair of HBV-infected twins.
      METHODS: The gene expression profile was compared in a pair of HBV-infected
      twins. RESULTS: The twins displayed different disease outcomes. One acquired
      natural immunity against HBV, whereas the other became a chronic HBV carrier.
      Eighty-eight and forty-six genes were found to be up- or down-regulated in their
      PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-alphaIP1)
      that expressed at a higher level in the HBV-immune twins was identified and four
      pairs of siblings with HBV immunity by RT-PCR. However, upon HBV core antigen
      stimulation, TNF-alphaIP1 was downregulated in PBMCs from subjects with immunity,
      whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis
      revealed a K+ channel tetramerization domain in TNF-alphaIP1 that shares a
      significant homology with some human, mouse, and C elegan proteins. CONCLUSION:
      TNF-alphaIP1 may play a role in the innate immunity against HBV.

PMID- 16437681
TI  - Application of restriction display PCR technique in the preparation of cDNA
      microarray probes.
AB  - AIM: To develop a simplified and efficient method for the preparation of
      hepatitis C virus (HCV) cDNA microarray probes. METHODS: With the technique of
      restriction display PCR (RD-PCR), restriction enzyme Sau3A I was chosen to digest
      the full-length HCV cDNAs. The products were classified and re-amplified by RD
      PCR. We separated the differential genes by polyacrylamide gel electrophoresis
      and silver staining. Single bands cut out from the polyacrylamide gel were
      isolated. The third-round PCR was performed using the single bands as PCR
      template. The RD-PCR fragments were purified and cloned into the pMD18-T vector.
      The recombinant plasmids were extracted from positive clones, and the target gene
      fragments were sequenced. The cDNA microarray was prepared by spotting RD-PCR
      products to the surface of amino-modified glass slides using a robot. We
      validated the detection of microarray by hybridization and sequence analysis.
      RESULTS: A total of 24 different cDNA fragments ranging from 200 to 800 bp were
      isolated and sequenced, which were the specific gene fragments of HCV. These
      fragments could be further used as probes in microarray preparation. The
      diagnostic capability of the microarray was evaluated after the washing and
      scanning steps. The results of hybridization and sequence analysis showed that
      the specificity, sensitivity, accuracy, reproducibility, and linearity in
      detecting HCV RNA were satisfactory. CONCLUSION: The RD-PCR technique is of great
      value in obtaining a large number of size-comparable gene probes, which provides
      a speedy protocol in generating probes for the preparation of microarrays.
      Microarray prepared as such could be further optimized and applied in the
      clinical diagnosis of HCV.

PMID- 16437680
TI  - High affinity mouse-human chimeric Fab against hepatitis B surface antigen.
AB  - AIM: Passive immunotherapy using antibody against hepatitis B surface antigen
      (HBsAg) has been advocated in certain cases of Hepatitis B infection. We had
      earlier reported on the cloning and expression of a high affinity scFv derived
      from a mouse monoclonal (5S) against HBsAg. However this mouse antibody cannot be
      used for therapeutic purposes as it may elicit anti-mouse immune responses.
      Chimerization by replacing mouse constant domains with human ones can reduce the
      immunogenicity of this antibody. METHODS: We cloned the V(H) and V(L) genes of
      this mouse antibody, and fused them with CH1 domain of human IgG1 and C(L) domain
      of human kappa chain respectively. These chimeric genes were cloned into a
      phagemid vector. After initial screening using the phage display system, the
      chimeric Fab was expressed in soluble form in E. coli. RESULTS: The chimeric Fab
      was purified from the bacterial periplasmic extract. We characterized the
      chimeric Fab using several in vitro techniques and it was observed that the
      chimeric molecule retained the high affinity and specificity of the original
      mouse monoclonal. This chimeric antibody fragment was further expressed in
      different strains of E. coli to increase the yield. CONCLUSION: We have generated
      a mouse-human chimeric Fab against HBsAg without any significant loss in binding
      and epitope specificity. This chimeric Fab fragment can be further modified to
      generate a full-length chimeric antibody for therapeutic uses.

PMID- 16437682
TI  - Response of porcine hepatocytes in primary culture to plasma from severe viral
      hepatitis patients.
AB  - AIM: To observe the effects of plasma from patients with severe viral hepatitis
      (SVHP) on the growth and metabolism of porcine hepatocytes and the clinical
      efficiency of bioartificial liver device. METHODS: Hepatocytes were isolated from
      male porcines by collagenase perfusion. The synthesis of DNA and total protein,
      leakages of AST and LDH, changes in glutathione (GSH), catalase and morphology of
      porcine hepatocytes exposed to SVHP were investigated to indicate the effect of
      plasma from patients with severe hepatitis on the growth, injury, detoxification,
      and morphology of porcine hepatocytes. RESULTS: The synthesis of DNA and protein
      was inhibited in the medium containing 100% SVHP compared to the controls. The
      leakages of LDH and AST increased in porcine hepatocytes following exposure to
      100% SVHP for 5 h. The difference between 100% SVHP and 10% newborn calf serum
      (NCS) was significant in t-test (LDH: t = 24.552, P = 0.001; AST: t = 4.169, P =
      0.014). After exposure to SVHP for 24 h, alterations in GSH status were
      significant (F = 2.746, P<0.05) between porcine hepatocytes in 100% SVHP and 10%
      NCS, but no alteration occurred in the culture medium after 48 h (F = 4.378,
      P<0.05). A similar profile was observed in catalase activity. Many round vacuoles
      were observed in porcine hepatocytes cultured in SVHP. The membranes of these
      cells became indistinct and almost all the cells died on d 5. CONCLUSION: Plasma
      from patients with severe hepatitis inhibits the growth, injures membrane,
      disturbs GSH homeostasis and induces morphological changes of porcine
      hepatocytes. It is suggested that SVHP should be pretreated to reduce the toxin
      load and improve the performance of porcine hepatocytes in extracorporeal liver
      support devices.

PMID- 16437683
TI  - Hepatitis C virus infection down-regulates the expression of peroxisome
      proliferator-activated receptor alpha and carnitine palmitoyl acyl-CoA
      transferase 1A.
AB  - AIM: To elucidate the role of the peroxisome proliferator-activated receptor
      alpha (PPARalpha) and its target gene carnitine palmitoyl acyl-CoA transferase 1A
      (CPT1A) in the pathogenesis of hepatitis C virus (HCV) infection. METHODS: Liver
      samples were collected from the patients with chronic HCV infection and controls.
      HepG2 cells were transfected with vector pEF352neo carrying. Two independent
      clones (clone N3 and N4) stably expressing HCV core protein were analyzed. Total
      RNA was extracted from cells and liver tissues. PPARalpha and CPT1A mRNAs were
      quantified by real-time polymerase chain reaction (PCR) using SYBR Green Master.
      Total extracted proteins were separated by polyacrylamide gel electrophoresis,
      and electroblotted. Membranes were incubated with the anti-PPARalpha antibody,
      then with a swine anti-rabbit IgG conjugated to horseradish peroxidase for
      PPARalpha. Protein bands were revealed by an enhanced chemiluminescence reaction
      for PPARalpha. For immunohistochemical staining of PPARalpha, sections were
      incubated with the primary goat polyclonal antibody directed against PPARalpha at
      room temperature. RESULTS: Real-time PCR indicated that the PPARalpha level and
      expression level of CPT1A gene in hepatitis C patients lowered significantly as
      compared with the controls (1.8+/-2.8 vs 13+/-3.4, P = 0.0002; 1.1+/-1.5 vs 7.4+/
      1, P = 0.004). Western blot results showed that the level of PPARalpha protein in
      the livers of hepatitis C patients was lower than that in controls (2.3+/-0.3 vs
      3.6+/-0.2, P = 0.009). The immunohistochemical staining results in chronic
      hepatitis C patients indicated a decrease in PPARalpha staining in hepatocytes
      compared with those in the control livers. The in vitro studies found that in the
      N3 and N4 colon stably expressing HCV core protein, the PPARalpha mRNA levels
      were significantly lower than that in the controls. CONCLUSION: The impaired
      intrahepatic PPARalpha expression is associated with the pathogenic mechanism in
      hepatic injury during chronic HCV infection. HCV infection reduced the expression
      of PPARalpha and CPT1A at the level of not only mRNAs but also proteins.
      PPARalpha plays an important role in the pathogenesis of chronic HCV infection,
      but the impaired function of this nuclear receptor in HCV infection needs further
      studies.

PMID- 16437684
TI  - Cytoskeleton reorganization and ultrastructural damage induced by gliadin in a
      three-dimensional in vitro model.
AB  - AIM: To evaluate the interplay between gliadin and LoVo cells and the direct
      effect of gliadin on cytoskeletal patterns. METHODS: We treated LoVo
      multicellular spheroids with digested bread wheat gliadin in order to investigate
      their morphology and ultrastructure (by means of light microscopy and scanning
      electron microscopy), and the effect of gliadin on actin (phalloidin
      fluorescence) and the tight-junction protein occludin and zonula occluden-1.
      RESULTS: The treated spheroids had deep holes and surface blebs, whereas the
      controls were smoothly surfaced ovoids. The incubation of LoVo spheroids with
      gliadin decreased the number of intracellular actin filaments, impaired and
      disassembled the integrity of the tight-junction system. CONCLUSION: Our data
      obtained from an "in vivo-like" polarized culture system confirm the direct
      noxious effect of gliadin on the cytoskeleton and tight junctions of epithelial
      cells. Unlike two-dimensional cell culture systems, the use of multicellular
      spheroids seems to provide a suitable model for studying cell-cell interactions.

PMID- 16437685
TI  - Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil
      inhibit proliferation of human intrahepatic biliary epithelial cells in vitro.
AB  - AIM: To investigate the effect of cyclosporine A (CsA), FK-506, and mycophenolate
      mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human
      intrahepatic biliary epithelial cells (BECs) in vitro. METHODS: BECs were
      isolated from six human liver tissuespecimens with the immunomagnetic separation
      method and treated with different concentrations of CsA, FK-506, RAD, and MMF in
      vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after
      treatment, respectively. One-way analysis of variance was used to analyze the
      results. Expression of CK 19 in BECs was monitored by flow cytometry and Western
      blot. RESULTS: Six lines of BECs were established. They survived for 4-18 wk in
      vitro. Flow cytometry analysis showed that these cells always expressed CK19.
      CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent
      manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit
      proliferation of BECs (P<0.05) was 500, 100, 0.25, and 100 mug/L, respectively.
      However, the expression of CK19 by BECs was not changed. CONCLUSION: CsA, FK-506,
      RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in
      vitro, while RAD has the strongest growth-inhibitory effect. Their possible
      effects on liver regeneration and bile duct injury in transplant patients should
      be further investigated.

PMID- 16437686
TI  - Protective effects of Asian green vegetables against oxidant induced
      cytotoxicity.
AB  - AIM: To evaluate the antioxidant and phase II detoxification enzyme inducing
      ability of green leaf vegetables consumed in Asia. METHODS: The antioxidant
      properties of six commonly consumed Asian vegetables were determined using the
      ABTS, DPPH, deoxyribose, PR bleaching and iron- ascorbate induced lipid
      peroxidation assay. Induce of phase II detoxification enzymes was also determined
      for each respective vegetable extract. Protection against authentic ONOO- and
      HOCl mediated cytotoxicity in human colon HCT116 cells was determined using the
      MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) viability
      assay. RESULTS: All of the extracts derived from green leaf vegetables exhibited
      antioxidant properties, while also having cytoprotective effects against ONOO-
      and HOCl mediated cytotoxicity. In addition, evaluation of the phase II enzyme
      inducing ability of each extract, as assessed by quinone reductase and
      glutathione-S-transferase activities, showed significant variation between the
      vegetables analyzed. CONCLUSION: Green leaf vegetables are potential sources of
      antioxidants and phase II detoxification enzyme inducers in the Asian diet. It is
      likely that consumption of such vegetables is a major source of beneficial
      phytochemical constituents that may protect against colonic damage.

PMID- 16437687
TI  - Detection and identification of intestinal pathogenic bacteria by hybridization
      to oligonucleotide microarrays.
AB  - AIM: To detect the common intestinal pathogenic bacteria quickly and accurately.
      METHODS: A rapid (<3 h) experimental procedure was set up based upon the gene
      chip technology. Target genes were amplified and hybridized by oligonucleotide
      microarrays. RESULTS: One hundred and seventy strains of bacteria in pure culture
      belonging to 11 genera were successfully discriminated under comparatively same
      conditions, and a series of specific hybridization maps corresponding to each
      kind of bacteria were obtained. When this method was applied to 26 divided
      cultures, 25 (96.2%) were identified. CONCLUSION: Salmonella sp., Escherichia
      coli, Shigella sp., Listeria monocytogenes, Vibrio parahaemolyticus,
      Staphylococcus aureus, Proteus sp., Bacillus cereus, Vibrio cholerae,
      Enterococcus faecalis, Yersinia enterocolitica, and Campylobacter jejuni can be
      detected and identified by our microarrays. The accuracy, range, and
      discrimination power of this assay can be continually improved by adding further
      oligonucleotides to the arrays without any significant increase of complexity or
      cost.

PMID- 16437688
TI  - Morphological and serum hyaluronic acid, laminin and type IV collagen changes in
      dimethylnitrosamine-induced hepatic fibrosis of rats.
AB  - AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and
      type IV collagen changes in hepatic fibrosis of rats induced by
      dimethylnitrosamine (DMN). METHODS: The rat model of liver fibrosis was induced
      by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The
      liver/weight index and morphological changes were examined under electron
      microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle
      actin alpha-SMA staining as well as Sirius-red and HE staining. RESULTS: The
      levels of serum HA, type IV collagen and LN significantly increased from d 7 to d
      28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In
      the model group, the rat liver stained with HE and Sirius-red showed evident
      hemorrhage and necrosis in the central vein of hepatic 10 lobules on d 7. Thin
      fibrotic septa were formed joining central areas of the liver on d 14. The number
      of alpha-SMA positive cells was markedly increased in the model group.
      Transitional hepatic stellate cells were observed under electron microscope. All
      rats in the model group showed micronodular fibrosis in the hepatic parenchyma
      and a network of alpha-SMA positive cells. Typical myofibroblasts were embedded
      in the core of a fibrous septum. Compared to the control group, the area-density
      percentage of collagen fibrosis and pathologic grading were significantly
      different in the model group (P<0.05) on different d (7, 14, and 28). The area
      density percentage of collagen fibrosis in hepatic tissue had a positive
      correlation with the levels of serum HA, LN, and type IV collagen. CONCLUSION:
      The morphological and serum HA, type IV collagen, and LN are changed in DMN
      induced liver fibrosis in rats.

PMID- 16437689
TI  - Management of hilar cholangiocarcinoma in the North of England: pathology,
      treatment, and outcome.
AB  - AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin
      tumor) in a single tertiary referral center. METHODS: The notes of all patients
      with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8
      year period were identified and retrospectively reviewed. Presentation,
      management and outcome were assessed. RESULTS: Seventy-five patients were
      identified. The median age was 64 years (range 34-84 years). Male to female ratio
      was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients
      referred were under Bismuth classification 3a, 3b or 4. Seventy patients required
      biliary drainage, 65 patients required 152 percutaneous drainage procedures, and
      25 had other complications. Forty-one patients had 51 endoscopic drainage
      procedures performed (15 failed). Of these, 36 subsequently required percutaneous
      drainage. The median number of drainage procedures for all patients was three, 18
      patients underwent resection (24%), nine had major complications and three died
      post-operatively. The 5-year survival rate was 4.2% for all patients, 21% for
      resected patients and 0% for those who did not undergo resection (P = 0.0021).
      The median number of admissions after diagnosis in resected patients was two and
      three in non-resected patients (P<0.05). Twelve patients had external-beam
      radiotherapy, seven brachytherapy, and eight chemotherapy. There was no
      significant benefit in terms of survival (P = 0.46) or hospital admissions.
      CONCLUSION: Resection increases survival but carries the risk of significant
      morbidity and mortality. Percutaneous biliary drainage is almost always necessary
      and endoscopic drainage should be avoided if possible.

PMID- 16437690
TI  - Distribution and effects of polymorphic RANTES gene alleles in HIV/HCV
      coinfection -- a prospective cross-sectional study.
AB  - AIM: Chemokines and their receptors are crucial for immune responses in HCV and
      HIV infection. RANTES gene polymorphisms lead to altered gene expression and
      influence the natural course of HIV infection. Therefore, these mutations may
      also affect the course of HIV/HCV coinfection. METHODS: We determined allele
      frequencies of RANTES-403 (G --> A), RANTES-28 (C --> G) and RANTES-IN1.1 (T -->
      C) polymorphisms using real-time PCR and hybridization probes in patients with
      HIV (n = 85), HCV (n = 112), HIV/HCV coinfection (n = 121), and 109 healthy
      controls. Furthermore, HIV and HCV loads as well as CD4(+) and CD8(+) cell counts
      were compared between different RANTES genotypes. RESULTS: Frequencies of RANTES
      403 A, RANTES-28 G and RANTES-IN1.1 C alleles were higher in HIV infected
      patients than in healthy controls (-403: 28.2% vs 15.1%, P = 0.002; -28: 5.4% vs
      2.8%, not significant; IN1.1: 19.0% vs 11.0%, P = 0.038). In HIV/HCV coinfected
      patients, these RANTES alleles were less frequent than in patients with HIV
      infection alone (15.4% P = 0.002; 1.7%; P = 0.048; 12.0%; not significant).
      Frequencies of these alleles were not significantly different between HIV/HCV
      positive patients, HCV positive patients and healthy controls. CONCLUSION: All
      three RANTES polymorphisms showed increased frequencies of the variant allele
      exclusively in patients with HIV monoinfection. The finding that the frequencies
      of these alleles remained unaltered in HIV/HCV coinfected patients suggests that
      HCV coinfection interferes with selection processes associated with these alleles
      in HIV infection.

PMID- 16437691
TI  - Elevated plasma von Willebrand factor levels in patients with active ulcerative
      colitis reflect endothelial perturbation due to systemic inflammation.
AB  - AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with
      ulcerative colitis (UC) and to investigate their relationship with disease
      activity, systemic inflammation and coagulation activation. METHODS: In 46
      patients with ulcerative colitis (active in 34 patients), clinical data were
      gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and
      fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at
      baseline and after 12 wk of treatment. Plasma vWF levels were also determined in
      52 healthy controls (HC). The relationship of plasma vWF levels with disease
      activity, disease extent, response to therapy, acute-phase reactants (APRs) and
      coagulation markers (COAGs) was assessed. RESULTS: The mean plasma vWF
      concentrations were significantly higher in active UC patients (143.38+/-63.73%)
      than in HC (100.75+/-29.65%, P = 0.001) and inactive UC patients (98.92+/-43.6%,
      P = 0.031). ESR, CRP and fibrinogen mean levels were significantly higher in
      active UC patients than in inactive UC patients, whereas there were no
      significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients
      with raised APRs had significantly higher mean plasma vWF levels than those with
      normal APRs (144.3% vs 96.2%, P = 0.019), regardless of disease activity.
      Although the mean plasma vWF levels were higher in UC patients with raised COAGs
      than in those with normal COAGs, irrespective of disease activity, the difference
      was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted
      between plasma vWF levels and disease extent. After 12 wk of treatment,
      significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were
      noted only in UC patients with clinical and endoscopic improvement. CONCLUSION:
      Our data indicate that increased plasma vWF levels correlate with active
      ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels
      in ulcerative colitis possibly reflect an acute-phase response of the perturbed
      endothelium due to inflammation. In UC patients, plasma vWF levels may be another
      useful marker of disease activity or response to therapy.

PMID- 16437692
TI  - Involvement of serum retinoids and Leiden mutation in patients with esophageal,
      gastric, liver, pancreatic, and colorectal cancers in Hungary.
AB  - AIM: To analyze the serum levels of retinoids and Leiden mutation in patients
      with esophageal, gastric, liver, pancreatic, and colorectal cancers. METHODS: The
      changes in serum levels of retinoids (vitamin A, alpha- and beta-carotene, alpha-
      and beta-cryptoxanthin, zeaxanthin, lutein) and Leiden mutation were measured by
      high liquid performance chromatography (HPLC) and polymerase chain reaction (PCR)
      in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5),
      liver (8/7), pancreatic (6/4), and colorectal (30/21 including 9 patients
      suffering from in situ colon cancer) cancer. Fifty-seven healthy subjects (in
      matched groups) for controls of serum retinoids and 600 healthy blood donors for
      Leiden mutation were used. RESULTS: The serum levels of vitamin A and zeaxanthin
      were decreased significantly in all groups of patients with gastrointestinal (GI)
      tumors except for vitamin A in patients with pancreatic cancer. No changes were
      obtained in the serum levels of alpha- and beta-carotene, alpha- and beta
      cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of
      Leiden mutation significantly increased in all groups of patients with GI cancer.
      CONCLUSION: Retinoids (as environmental factors) are decreased significantly with
      increased prevalence of Leiden mutation (as a genetic factor) in patients before
      the clinical manifestation of histologically different (planocellular and
      hepatocellular carcinoma, and adenocarcinoma) GI cancer.

PMID- 16437693
TI  - Helicobacter pylori upregulates prion protein expression in gastric mucosa: a
      possible link to prion disease.
AB  - AIM: Pathological prion protein (PrP(sc)) is responsible for the development of
      transmissible spongiform encephalopathies (TSE). While PrPc enters the organism
      via the oral route, less data is available to know about its uptake and the role
      of gastrointestinal inflammation on the expression of prion precursor PrPc, which
      is constitutively expressed in the gastric mucosa. METHODS: We studied PrPc
      expression in the gastric mucosa of 10 Helicobacter pylori-positive patients
      before and after successful H pylori eradication compared to non-infected
      controls using RT-PCR and Western blotting. The effect of central mediators of
      gastric inflammation, i.e., gastrin, prostaglandin E(2) (PGE(2)), tumor necrosis
      factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta) on PrPc expression was
      analyzed in gastric cell lines. RESULTS: PrPc expression was increased in H
      pylori-infection compared with non-infected controls and decreased to normal
      after successful eradication. Gastrin, PGE(2), and IL-1beta dose-dependently
      upregulated PrPc in gastric cells, while TNF-alpha had no effect. CONCLUSION: H
      pylori infection leads to the upregulation of gastric PrPc expression. This can
      be linked to H pylori induced hypergastrinemia and increased mucosal PGE(2) and
      IL-1beta synthesis. H pylori creates a milieu for enhanced propagation of prions
      in the gastrointestinal tract.

PMID- 16437695
TI  - Phagocytic and oxidative burst activity of neutrophils in the end stage of liver
      cirrhosis.
AB  - AIM: To evaluate the phagocytic activity and neutrophil oxidative burst in liver
      cirrhosis. METHODS: In 45 patients with advanced postalcoholic liver cirrhosis
      (aged 45+/-14 years) and in 25 healthy volunteers (aged 38+/-5 years), the
      percentage of phagocytizing cells after in vitro incubation with E. coli
      (Phagotest Kit), phagocytic activity (mean intensity of fluorescence, MIF) and
      the percentage of neutrophil oxidative burst (Bursttest Kit), and the level of
      free oxygen radical production (MIF of Rodamine 123) were analyzed by flow
      cytometry. The levels of soluble sICAM-1, sVCAM-1, sP-selectin, sE-selectin, sL
      selectin, and TNF-alpha were determined in blood serum. RESULTS: The percentage
      of E. coli phagocytizing neutrophils in liver cirrhosis patients was comparable
      to that in healthy subjects. MIF of neutrophil -- ingested E. coli was higher in
      patients with liver cirrhosis. The oxidative burst in E. coli phagocytizing
      neutrophils generated less amount of active oxygen compounds in liver cirrhosis
      patients (MIF of R123: 24.7+/-7.1 and 29.7+/-6.6 in healthy, P<0.01). Phorbol
      myristate acetate (PMA) -- stimulated neutrophilsproduced less reactive oxidants
      in liver cirrhosis patients than in healthy subjects (MIF of R123: 42.7+/-14.6 vs
      50.2+/-13.3, P<0.01). A negative correlation was observed between oxidative burst
      MIF of PMA-stimulated neutrophils and ALT and AST levels (r -0.35, P<0.05; r-0.4,
      P<0.03). sVCAM-1, sICAM-1, sE-selectin concentrations correlated negatively with
      the oxygen free radical production (MIF of R123) in neutrophils after PMA
      stimulation in liver cirrhosis patients (r-0.45, P<0.05; r-0.41, P<0.05; r-0.39,
      P<0.05, respectively). CONCLUSION: Neutrophil metabolic activity diminishes
      together with the intensification of liver failure. The metabolic potential of
      phagocytizing neutrophils is significantly lower in liver cirrhosis patients,
      which can be one of the causes of immune mechanism damage. The evaluation of
      oxygen metabolism of E. coli-stimulated neutrophils reveals that the amount of
      released oxygen metabolites is smaller in liver cirrhosis patients than in
      healthy subjects.

PMID- 16437694
TI  - Asthma and gastroesophageal reflux disease: effect of long-term pantoprazole
      therapy.
AB  - AIM: To define the prevalence of gastroesophageal reflux disease (GERD) in mild
      persistent asthma and to value the effect of pantoprazole therapy on asthmatic
      symptoms. METHODS: Seven of thirty-four asthmatic patients without GERD served as
      the non-GERD control group. Twenty-seven of thirty-four asthmatic patients had
      GERD (7/27 also had erosive esophagitis, sixteen of them presented GERD symptoms.
      An upper gastrointestinal endoscopy was performed in all the subjects to obtain
      five biopsy specimens from the lower 5 cm of the esophagus. Patients were
      considered to have GERD when they had a dilation of intercellular space (DIS)
      >0.74 mum at transmission electron microscopy. Patients with GERD were treated
      with pantoprazole, 80 mg/day. Forced expiratory volume in one second (FEV1) was
      performed at entry and after 6 mo of treatment. Asthmatic symptoms were recorded.
      The required frequency of inhaling rapid acting beta2-agonists was self-recorded
      in the patients' diaries. RESULTS: Seven symptomatic patients presented erosive
      esophagitis. Among the 18 asymptomatic patients, 11 presented DIS, while all
      symptomatic patients showed ultrastructural esophageal damage. Seven asymptomatic
      patients did not present DIS. At entry the mean of FEV(1) was 1.91 L in
      symptomatic GERD patients and 1.88 L in asymptomatic GERD patients. After the
      treatment, 25 patients had a complete recovery of DIS and reflux symptoms. Twenty
      three patients presented a regression of asthmatic symptoms with normalization of
      FEV(1). Four patients reported a significant improvement of symptoms and their
      FEV(1) was over 80%. CONCLUSION: GERD is a highly prevalent condition in asthma
      patients. Treatment with pantoprazole (80 mg/day) determines their improvement
      and complete regression.

PMID- 16437696
TI  - Possible involvement of leptin and leptin receptor in developing gastric
      adenocarcinoma.
AB  - AIM: To investigate the expression of leptin and leptin receptor (ob-R) in
      intestinal-type gastric cancer and precancerous lesions, and to explore the
      possible mechanism and role of the leptin system in developing intestinal-type
      gastric adenocarcinoma. METHODS: Immunohistochemistry was performed to examine
      the expression of leptin and leptin receptor in archival samples of gastric
      adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and
      mild to severe gastric epithelial dysplasia. Positive staining was identified and
      percentage of positive staining was graded. RESULTS: Dual expression of leptin
      and leptin receptor were detected in 80% (16/20) intestinal metaplasia, 86.3%
      (25/30) mild gastric epithelial dysplasia, 86.7% (26/30) moderate gastric
      epithelial dysplasia, 93.3% (28/30) severe gastric epithelial dysplasia, 91.3%
      (55/60) intestinal-type gastric adenocarcinoma and 30.0% (9/30) diffuse-type
      gastric carcinoma. The percentage of dual expression of leptin and leptin
      receptor in intestinal-type gastric adenocarcinoma was significantly higher than
      that in diffuse-type gastric adenocarcinoma (c2 = 37.022, P<0.01). CONCLUSION:
      Our results indicate the presence of an autocrine loop of leptin system in the
      development of intestinal-type gastric adenocarcinoma.

PMID- 16437697
TI  - New tumor-associated antigen SC6 in pancreatic cancer.
AB  - AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by
      monoclonal antibody (MAb) in patients with pancreatic cancer and other malignant
      or benign diseases and to understand whether SC6-Ag has any clinical significance
      in distinguishing pancreatic cancer from other gastrointestinal diseases.
      METHODS: Six hundred and ninety-five serum specimens obtained from 115 patients
      with pancreatic cancer, 154 patients with digestive cancer and 95 patients with
      non-digestive cancer were used and classified in this study. Serum specimens
      obtained from 140 patients with benign digestive disease and 89 patients with non
      benign digestive disease served as controls. Ascites was tapped from 16
      pancreatic cancer patients, 19 hepatic cancer patients, 16 colonic cancer
      patients, 10 gastric cancer and 6 severe necrotic pancreatitis patients. The
      samples were quantitated by solid-phase radioimmunoassay. The cut-off values (CV)
      of 41, 80, and 118 U/mL were used. RESULTS: The average intra- and interassay CV
      detected by immunoradiometric assay of SC6-Ag was 5.4% and 8.7%, respectively.
      The sensitivity and specificity were 73.0% and 90.9% respectively. The levels in
      most malignant and benign cases were within the normal upper limit. Among the 16
      pancreatic cancer cases, the concentration of SC6-Ag in ascites was over the
      normal range in 93.8% patients. There was no significant difference in the
      concentration of SC6-Ag. Decreased expression of SC6-Ag in sera was significantly
      related to tumor differentiation. The concentration of SC6-Ag was higher in
      patients before surgery than after surgery. The specificity of SC6-Ag and CA19-9
      was significantly higher than that of ultrasound and computer tomography (CT) in
      pancreatic cancer patients. Higher positive predictive values were indicated in
      92.3% SC6-Ag and 88.5% CA19-9, but lower in 73.8% ultrasound and 76.2% CT.
      CONCLUSION: The combined test of SC6-Ag and CA19-9 may improve the diagnostic
      rate of primary cancer. The detection of SC6-Ag is valuable in the diagnosis of
      pancreatic cancer before and after surgery.

PMID- 16437698
TI  - Liver transplantation for metastatic neuroendocrine tumor: a case report and
      review of the literature.
AB  - Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic
      neuroendocrine tumors. The WHO has updated the classification of these lesions
      and has abandoned the term "carcinoid". Both types of tumors are divided into
      functional and non-functional tumors. They are characterized by slow growth and
      frequent metastasis to the liver and may be limited to the liver for long
      periods. The therapeutic approach to hepatic metastases should consider the
      number and distribution of the liver metastases as well as the severity of
      symptoms related to hormone production and tumor bulk. Surgery is generally
      considered as the first line therapy. In patients with unresectable liver
      metastases, alternative treatments are dependent on the type and the growth rate.
      Initial treatments consist of long acting somatostatin analogs and/or interferon.
      Streptozocin-based chemotherapy is usually reserved for symptomatic patients with
      rapidly advancing disease, but generally the therapy is poorly tolerated and its
      effects are short-lived. Locoregional therapy directed such as hepatic-artery
      embolization and chemoembolization, radiofrequency thermal ablation and
      cryosurgery, is often used instead of systemic therapy, if the disease is limited
      to the liver. However, liver transplantation should be considered in patients
      with neuroendocrine metastases to the liver that are not accessible to curative
      or cytoreductive surgery and if medical or locoregional treatment has failed and
      if there are life threatening hormonal symptoms. We report a case of liver
      transplantation for metastatic neuroendocrine tumor of unknown primary source and
      provide a detailed review of the world literature on this controversial topic.

PMID- 16437699
TI  - Successful outcome following resection of a pancreatic liposarcoma with solitary
      metastasis.
AB  - Liposarcomas are rare soft tissue tumors, commonly affecting the lower limbs and
      less commonly the retroperitoneum. Although other organs can be affected, the
      pancreas is one of the rarest, and metastasis at presentation has never been
      reported. We describe the case of a 76-year-old gentleman presenting with
      abdominal pain and an abdominal mass. Imaging confirmed a primary tumor in the
      body and tail of the pancreas, with a metastatic deposit in the mesentery
      adjacent to the second part of the duodenum. Biopsy confirmed a liposarcoma, and
      subsequently a complete surgical excision was achieved. He then received adjuvant
      radiotherapy and has remained disease free for the next 26 mo.

PMID- 16437700
TI  - Recurrent severe gastrointestinal bleeding and malabsorption due to extensive
      habitual megacolon.
AB  - Dilatation of the colon and the rectum, which is not attributable to
      aganglionosis, is a rare finding and can be the result of intractable chronic
      constipation. We report a rare case of a 29-year-old male patient with impressive
      megacolon, in whom Hirschsprung's or Chagas disease was ruled out. In the present
      case, dilatation of the colon was most likely due to a behavioral disorder with
      habitual failure of defecation. Chronic stool retention led to a bizarre bulging
      of the large bowel with displacement of the other abdominal organs and severe
      occult blood loss. Because of two episodes of life-threatening gastrointestinal
      bleeding despite conventional treatment of constipation, a surgical approach for
      bowel restoration was necessary. Temporary loop ileostomy had to be performed for
      de-pressurization of the large bowel and the subsequent possibility for effective
      antegrade colonic lavage to remove impacted stools. Shortly after the operation,
      the patient was healthy and could easily manage the handling of the ileostomy.
      However, the course of the megacolon in this young adult cannot be predicted and
      the follow-up will have to reveal if regression of this extreme colonic
      distension with reestablishment of regular rectal perception will occur.

PMID- 16437701
TI  - Does Fasciola hepatica infection modify the response of acute hepatitis C virus
      infection to IFN-alpha treatment?
AB  - Immunologic response to acute hepatitis C is mainly a Th1 response, whereas
      fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha
      has immunomodulatory effects and enhances Th1 immune response. Fasciola infection
      could theoretically interfere with the Th1 immune response, even when acquired
      after an initial response to interferon-alpha treatment for acute hepatitis C
      virus (HCV) infection. We report here the case of a male patient who acquired
      Fasciola hepatica infection after an initial response to IFN-alpha therapy with a
      favorable outcome.

PMID- 16437702
TI  - Autosomal dominant polycystic liver disease in a family without polycystic kidney
      disease associated with a novel missense protein kinase C substrate 80K-H
      mutation.
AB  - Polycystic liver disease (PLD) is characterized by the presence of multiple bile
      duct-derived epithelial cysts scattered in the liver parenchyma. PLD can manifest
      itself in patients with severe autosomal dominant polycystic kidney disease
      (ADPKD). Isolated autosomal dominant polycystic liver disease (ADPLD) is
      genetically distinct from PLD associated with ADPKD, although it may have similar
      pathogenesis and clinical manifestations. Recently, mutations in two causative
      genes for ADPLD, independently from ADPKD, have been identified. We report here a
      family (a mother and her daughter) with a severe form of ADPLD not associated
      with ADPKD produced by a novel missense protein kinase C substrate 80K-H (PRKCSH)
      mutation (R281W). This mutation causes a severe phenotype, since the two affected
      subjects manifested signs of portal hypertension. Doppler sonography, computed
      tomography (CT) and magnetic resonance (MR) imaging are effective in documenting
      the underlying lesions in a non-invasive way.

PMID- 16437703
TI  - Robotic-assisted laparoscopic resection of ectopic pancreas in the posterior wall
      of gastric high body: case report and review of the literature.
AB  - Minimally invasive surgery has revolutionized the treatment of gastrointestinal
      tumors. Submucosal tumors of the stomach can be resected using laparoscopic
      techniques. We report here a case of ectopic pancreas tissue in the gastric wall
      that was removed using robotic-assisted laparoscopic resection. The patient was a
      15-year-old female who presented with abdominal discomfort and tarry stools.
      Laboratory analysis showed iron deficiency anemia. Preoperative endoscopy
      revealed a submucosal lesion in the posterior wall of the gastric high body.
      Intraoperative upper endoscopy clearly located the lesion. A robotic-assisted
      laparoscopic wedge resection of the putative gastric submucosal tumor was
      performed. The pathology results showed an ectopic pancreas. The patient had an
      uneventful recovery and we believe that this is a valid treatment option for this
      benign condition.

PMID- 16437704
TI  - Isolated rectal diverticulum complicating with rectal prolapse and outlet
      obstruction: case report.
AB  - The occurrence of rectal diverticula is very rare, with only sporadic reports in
      the literature since 1911. Symptomatic rectal diverticula are encountered even
      less frequently. Treatments of these complicated events range from conservative
      treatments to major surgical interventions. We present a hitherto unreported
      occurrence of isolated rectal diverticulum complicated with rectal prolapse and
      outlet obstruction. Delorme's procedure resulted in subsidence of symptoms and
      resolution of the diverticulum. It provides a minimal invasive surgical technique
      to successfully address the reported malady.

PMID- 16437705
TI  - Mesenteric and portal vein thrombosis associated with hyperhomocysteinemia and
      heterozygosity for factor V Leiden mutation.

PMID- 16437706
TI  - Fenofibrate-induced liver injury.

PMID- 16437708
TI  - Expression of human chorionic gonadotropin, CD44v6 and CD44v4/5 in esophageal
      squamous cell carcinoma.
AB  - AIM: To study the relationship between the expression of human chorionic
      gonadotropin (HCG), CD44v6, CD44v4/5 and the infiltration, metastasis of
      esophageal squamous cell carcinoma. METHODS: By labeled streptavidin-biotin
      technique, the expressions of HCG, CD44v6, and CD44v4/5 in 42 patients with
      esophageal squamous cell carcinoma were examined. RESULTS: The positive rate of
      HCG expression in patients with lymph node metastasis was 85.71% (18/21), higher
      than that (57.14%, 12/21) in those without lymph node metastasis (P<0.05). The
      positive rate of CD44v6 expression was 71.43% (15/21) in lymph node metastasis
      group, and 38.09% (8/21) in non-metastasis group; there was a significant
      difference between the two groups (P<0.05). The positive rate of CD44v4/5
      expression was 76.19% (16/21) in lymph node metastasis group, and 42.86% (9/21)
      in non-metastasis group; there was also a significant difference between them
      (P<0.05). From grade I to grade III in differentiation, the positive rate of HCG
      expression was 84.62% (11/13), 70.59% (12/17) and 58.33% (7/12), respectively;
      there was no significant difference among them (P>0.05). The positive rate of
      CD44v6 expression in grades I-III of cancer tissues was 76.92% (10/13), 52.94%
      (9/17), and 33.33% (4/12) respectively; there was no significant difference among
      them. The positive rate of CD44v4/5 expression in grades I-III of cancer tissues
      was 69.23% (9/13), 64.71% (11/17), and 41.67% (5/12) respectively; there was no
      significant difference among the three groups. There was no correlation between
      the positive rates of HCG and CD44v6, CD44v4/5 expression. Cancer cells in
      carcinomatous emboli and those infiltrating into vascular wall strongly expressed
      HCG, CD44v6, and CD44v4/5. CONCLUSION: Expression of HCG, CD44v6, and CD44v4/5 in
      esophageal squamous cell carcinoma is related to its infiltration and metastasis.
      HCG, CD44v6, and CD44v4/5 have different effects on the infiltration and
      metastasis of esophageal squamous cell carcinoma.

PMID- 16437707
TI  - Hepatocellular carcinoma: therapy and prevention.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors
      worldwide. The major etiologies and risk factors for the development of HCC are
      well defined and some of the multiple steps involved in hepatocarcinogenesis have
      been elucidated in recent years. Despite these scientific advances and the
      implementation of measures for the early detection of HCC in patients at risk,
      patient survival has not improved during the last three decades. This is due to
      the advanced stage of the disease at the time of clinical presentation and
      limited therapeutic options. The therapeutic options fall into five main
      categories: surgical interventions including tumor resection and liver
      transplantation, percutaneous interventions including ethanol injection and
      radiofrequency thermal ablation, transarterial interventions including
      embolization and chemoembolization, radiation therapy and drugs as well as gene
      and immune therapies. These therapeutic strategies have been evaluated in part in
      randomized controlled clinical trials that are the basis for therapeutic
      recommendations. Though surgery, percutaneous and transarterial interventions are
      effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and
      compensated underlying liver disease (cirrhosis Child A), at the time of
      diagnosis more than 80% patients present with multicentric HCC and advanced liver
      disease or comorbidities that restrict the therapeutic measures to best
      supportive care. In order to reduce the morbidity and mortality of HCC, early
      diagnosis and the development of novel systemic therapies for advanced disease,
      including drugs, gene and immune therapies as well as primary HCC prevention are
      of paramount importance. Furthermore, secondary HCC prevention after successful
      therapeutic interventions needs to be improved in order to make an impact on the
      survival of patients with HCC. New technologies, including gene expression
      profiling and proteomic analyses, should allow to further elucidate the molecular
      events underlying HCC development and to identify novel diagnostic markers as
      well as therapeutic and preventive targets.

PMID- 16437709
TI  - Gene expression profiling of gastric cancer by microarray combined with laser
      capture microdissection.
AB  - AIM: To examine the gene expression profile of gastric cancer (GC) by combination
      of laser capture microdissection (LCM) and microarray and to correlate the
      profiling with histological subtypes. METHODS: Using LCM, pure cancer cells were
      procured from 45 cancerous tissues. After procurement of about 5000 cells, total
      RNA was extracted and the quality of RNA was determined before further
      amplification and hybridization. One microgram of amplified RNA was converted to
      cDNA and hybridized to cDNA microarray. RESULTS: Among 45 cases, only 21 were
      qualified for their RNAs. A total of 62 arrays were performed. These included 42
      arrays for cancer (21 cases with dye-swab duplication) and 20 arrays for non
      tumorous cells (10 cases with dye-swab duplication) with universal reference.
      Analyzed data showed 504 genes were differentially expressed and could
      distinguish cancerous and non-cancerous groups with more than 99% accuracy. Of
      the 504 genes, trefoil factors 1, 2, and 3 were in the list and their expression
      patterns were consistent with previous reports. Immunohistochemical staining of
      trefoil factor 1 was also consistent with the array data. Analyses of the tumor
      group with these 504 genes showed that there were 3 subgroups of GC that did not
      correspond to any current classification system, including Lauren's
      classification. CONCLUSION: By using LCM, linear amplification of RNA, and cDNA
      microarray, we have identified a panel of genes that have the power to
      discriminate between GC and non-cancer groups. The new molecular classification
      and the identified novel genes in gastric carcinogenesis deserve further
      investigations to elucidate their clinicopathological significance.

PMID- 16437710
TI  - Effect of synbiotics on intestinal microflora and digestive enzyme activities in
      rats.
AB  - AIM: To investigate the effect of synbiotics, i.e. probiotics and prebiotics
      mixture, on the gut microbial ecology and digestive enzyme activities in rats.
      METHODS: Forty-eight SD rats weighing about 280 g were used in this study. Rats
      were divided into three groups according to the contents of probiotics and
      prebiotics mixture in the feed as control, low and high dose groups. The duration
      of the experiment was 8 wk. RESULTS: Compared with the control group, the fecal
      Lactobacillus and Bifidobacterium counts were significantly increased and the
      fecal Coliform organism counts were markedly reduced in the low and high dose
      groups. Concerning the digestive enzyme activity of jejunum, only lactase
      activity increased in low dose group. However, significant increase of lipase,
      lactase, sucrase, and isomaltase activities were observed in high dose group.
      CONCLUSION: Intake of low and high dosages of probiotics and prebiotics mixture
      significantly improved the ecosystem of the intestinal tract by increasing the
      probiotics population and digestive enzyme activities in rats.

PMID- 16437711
TI  - Hepatocyte cytoskeleton during ischemia and reperfusion--influence of ANP
      mediated p38 MAPK activation.
AB  - AIM: To determine functional consequences of this activation, whereby we focused
      on a potential regulation of the hepatocyte cytoskeleton during ischemia and
      reperfusion. METHODS: For in vivo experiments, animals received ANP (5 microg/kg)
      intravenously. In a different experimental setting, isolated rat livers were
      perfused with KH-buffer+/-ANP (200 nmol/L) +/-SB203580 (2 micromol/L). Livers
      were then kept under ischemic conditions for 24 h, and either transplanted or
      reperfused. Actin, Hsp27, and phosphorylated Hsp27 were determined by Western
      blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin
      distribution was determined by confocal microscopy. RESULTS: We first confirmed
      that ANP preconditioning leads to an activation of p38 MAPK and observed
      alterations of the cytoskeleton in hepatocytes of ANP-preconditioned organs. ANP
      induced an increase of hepatic F-actin after ischemia, which could be prevented
      by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia
      untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an
      increase in total Hsp27, whereas ANP preconditioning prohibited translocation but
      caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via
      p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580. CONCLUSION:
      This study reveals that ANP-mediated p38 MAPK activation leads to changes in
      hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and
      thereby for the first time shows functional consequences of ANP-induced hepatic
      p38 MAPK activation.

PMID- 16437712
TI  - Therapeutic effect of DA-9601 on chronic reflux gastritis induced by sodium
      taurocholate in rats.
AB  - AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate
      (TCA)-induced chronic reflux gastritis in SD rats. METHODS: In this study, we
      have investigated the therapeutic effects of DA-9601 on chronic erosive and
      atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking
      water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216%
      in rat chow), following the withdrawal of TCA treatment, resulted in a
      significant decrease in total length of erosions in rats in a dose-dependent
      manner. Furthermore, the indicators of atrophic gastritis, such as reduced
      mucosal thickness and reduction in the number of parietal cells, were improved by
      the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated
      inflammatory cell infiltration and the proliferation of collagenous fiber in the
      gastric mucosa. The improvement in the reduction of the gastric mucus was
      observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic
      effect of DA-9601 on experimental chronic erosive gastritis was superior to that
      of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal
      prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION:
      We suggest that DA-9601 is a promising agent for the treatment of chronic erosive
      and atrophic gastritis with an etiological factor of bile reflux. Increased
      mucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be
      therapeutic mechanisms for chronic erosive and atrophic gastritis.

PMID- 16437713
TI  - Superoxide dismutase prevents development of adenocarcinoma in a rat model of
      Barrett's esophagus.
AB  - AIM: To test whether antioxidant treatment could prevent the progression of
      Barrett's esophagus to adenocarcinoma. METHODS: In a rat model of
      gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric
      preservation, groups of 6-10 rats were randomized to receive treatment with
      superoxide dismutase (SOD) or vehicle and followed up for 4 mo. Rat's esophagus
      was assessed by histological analysis, superoxide anion and peroxinitrite
      generation, SOD levels and DNA oxidative damage. RESULTS: All rats undergoing
      esophagojejunostomy developed extensive esophageal mucosal ulceration and
      inflammation by mo 4. The process was associated with a progressive presence of
      intestinal metaplasia beyond the anastomotic area (9% 1st mo and 50% 4th mo) (94%
      at the anastomotic level) and adenocarcinoma (11% 1st mo and 60% 4th mo). These
      changes were associated with superoxide anion and peroxinitrite mucosal
      generation, an early and significant increase of DNA oxidative damage and a
      significant decrease in SOD levels (P<0.05). Exogenous administration of SOD
      decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the
      risk of developing intestinal metaplasia beyond the anastomotic area (odds ratio
      = 0.326; 95%CI: 0.108-0.981; P = 0.046), and esophageal adenocarcinoma (odds
      ratio = 0.243; 95%CI: 0.073-0.804; P = 0.021). CONCLUSION: Superoxide dismutase
      prevents the progression of esophagitis to Barrett's esophagus and adenocarcinoma
      in this rat model of gastrointestinal reflux, supporting a role of antioxidants
      in the chemoprevention of esophageal adenocarcinoma.

PMID- 16437714
TI  - Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in
      mice.
AB  - AIM: To investigate the in vivo effects of NK2 on liver regeneration after
      partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2
      transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was
      analyzed using histology and immunohistochemistry. Expressions of genes were
      analyzed using Northern blot analysis, immunoprecipitation and immunoblotting,
      and reverse transcriptase polymerase chain reaction assay. Kaplan-Meier method
      and the log-rank test were used for analyzing the survival after PH. Differences
      in the results of immunohistochemistry and percentage of liver regeneration was
      determined by the Student's t-test. RESULTS: More than half of NK2 transgenic
      mice died within 48 h after PH. After PH, increased deposition of small lipid
      droplets in hepatocytes was evident and hepatic proliferation was inhibited in
      NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor,
      c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The
      expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in
      liver tissues were prolonged in NK2 transgenic mice that died after PH.
      CONCLUSION: Our findings indicate that over-expression of NK2 inhibits liver
      regeneration after PH.

PMID- 16437715
TI  - Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its
      inhibition by DA-9601, an Artemisia asiatica extract.
AB  - AIM: To examine the effect of DA-9601, a new gastroprotective agent, on the
      vulnerability of ethanol-treated rat's stomach to naproxen (NAP). METHODS: Male
      Sprague-Dawley rats were pretreated with 1 mL of 50% ethanol twice a day for 5 d
      and then NAP (50 mg/kg) was administered. DA-9601 was administered 1 h before
      NAP. Four hours after NAP, the rats were killed to examine gross injury index
      (mm2), histologic change and to determine mucosal levels of malondialdehyde
      (MDA), prostaglandin E2 (PGE2), glutathione (GSH) and myeloperoxidase (MPO).
      RESULTS: Pretreatment of ethanol significantly increased NAP-induced gastric
      lesions, as well as an increase in MDA and MPO. On the contrary, mucosal PGE2 and
      GSH contents were decreased dramatically by ethanol pretreatment, which were
      aggravated by NAP. DA-9601 significantly reduced NAP-induced gastric injury
      grossly and microscopically, regardless of pretreatment with ethanol. DA-9601
      preserved, or rather, increased mucosal PGE2 and GSH in NAP-treated rats
      (P<0.05), with reduction in mucosal MDA and MPO levels. CONCLUSION: These results
      suggest that repeated alcohol consumption renders gastric mucosa more susceptible
      to NSAIDs though, at least in part, reduction of endogenous cytoprotectants
      including PGE2 and GSH, and increase in MPO activation, and that DA-9601, a new
      gastroprotectant, can reduce the increased vulnerability of ethanol consumers to
      NSAIDs-induced gastric damage via the mechanism in which PGE2 and GSH are
      involved.

PMID- 16437716
TI  - Colon-specific drug delivery systems based on cyclodextrin prodrugs: in vivo
      evaluation of 5-aminosalicylic acid from its cyclodextrin conjugates.
AB  - AIM: To investigate the release of cyclodextrin-5-aminosalicylic acid (CyD-5-ASA)
      in cecum and colon. METHODS: An anti-inflammatory drug 5-ASA was conjugated onto
      the hydroxyl groups of alpha-, beta- and gamma-cyclodextrins (CyDs) through an
      ester linkage, and the in vivo drug release behavior of these prodrugs in rat's
      gastrointestinal tract after the oral administration was investigated. RESULTS:
      The 5-ASA concentration in the rat's stomach and small intestine after the oral
      administration of CyD-5-ASA conjugate was much lower than that after the oral
      administration of 5-ASA alone. The lower concentration was attributable to the
      passage of the conjugate through the stomach and small intestine without
      significant degradation or absorption, followed by the degradation of the
      conjugate site-specific in the cecum and colon. The oral administration of CyD-5
      ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA
      alone. CONCLUSION: CyD-5-ASA conjugates may be used as prodrugs for colon
      specific drug delivery system.

PMID- 16437717
TI  - Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of
      human umbilical cord blood-derived mesenchymal stem cells into hepatocytes.
AB  - AIM: To investigate the differentiation of human umbilical cord blood (HUCB)
      derived mesenchymal stem cells (MSCs) into hepatocytes by induction of fibroblast
      growth factor-4 (FGF-4) and hepatocyte growth factor (HGF), and to find a new
      source of cell types for therapies of hepatic diseases. METHODS: MSCs were
      isolated by combining gradient density centrifugation with plastic adherence.
      When HUCB-derived MSCs reached 70% confluence, they were cultured in Iscove
      modified Dulbecco medium (IMDM) supplemented with 10 mL/L FBS, 20 ng/mL HGF and
      10 ng/mL FGF-4. The medium was changed every 4 d and stored for albumin, alpha
      fetoprotein (AFP) and urea assay. Expression of CK-18 was detected by
      immunocytochemistry. Glycogen storage in hepatocytes was determined by PAS
      staining. RESULTS: By combining gradient density centrifugation with plastic
      adherence, we could isolate MSCs from 25.6% of human umbilical cord blood. When
      MSCs were cultured with FGF-4 and HGF, approximately 63.6% of cells became small,
      round and epithelioid on d 28 by morphology. Compared with the control, the level
      of AFP increased significantly from d 12 to 18.20+/-1.16 microg/L (t = 2.884,
      P<0.05) in MSCs cultured with FGF-4 and HGF, and was higher (54.28+/-3.11
      microg/L) on d 28 (t = 13.493, P<0.01). Albumin increased significantly on d 16
      (t = 6.68, P<0.01) to 1.02+/-0.15 microg/mL, and to 3.63+/-0.30 microg/mL on d 28
      (t = 11.748, P<0.01). Urea (4.72+/-1.03 micromol/L) was detected on d 20 (t =
      4.272, P<0.01), and continued to increase to 10.28+/-1.06 micromol/L on d 28 (t =
      9.276, P<0.01). Cells expressed CK-18 on d 16. Glycogen storage was observed on d
      24. CONCLUSION: HUCB-derived MSCs can differentiate into hepatocytes by induction
      of FGF-4 and HGF. HUCB-derived MSCs are a new source of cell types for cell
      transplantation therapy of hepatic diseases.

PMID- 16437718
TI  - Effect of fish oil enriched enteral diet on inflammatory bowel disease tissues in
      organ culture: differential effects on ulcerative colitis and Crohn's disease.
AB  - AIM: To investigate the influence of fish oil enriched enteral diet on intestinal
      tissues taken from Crohn's disease (CD), ulcerative colitis (UC) and non-inflamed
      non-IBD control patients in vitro. METHODS: Colonoscopic biopsies from patients
      with active CD (n = 4), active UC (n = 7), and non-inflamed non-IBD control
      patients (n = 4) were incubated (three dilutions of 1:20, 1:10, and 1:5) with
      Waymouth's culture medium and enteral elemental diet (EO28, SHS, Liverpool, UK)
      modified in the fatty acid composition with fish oil (EF) in an organ culture
      system for 24 h. In each experimental set-up, incubation with Waymouth's medium
      alone as control was included. Tissue viability was assessed by adding
      bromodeoxyuridine (BrdU) to the culture fluid and immunohistochemically staining
      for BrdU uptake. Cytokine ratio of IL-1ra/IL-1beta (low ratio indicative of
      inflammation) and production of those cytokines as a percentage of medium control
      were assayed in the culture supernatant. RESULTS: Incubation of CD-affected
      tissue with EF (1:20, 1:10, and 1:5) modestly and non-significantly increased IL
      1ra/IL-1beta ratio as compared with medium control (CD 39.1+/-16.1; 26.5+/-7.8,
      47.1+/-16.8 vs control 13.0+/-2.2), but incubation of UC-affected tissues
      increased IL-1ra/IL-1beta ratio significantly in all three dilutions (UC 69.1+/
      32.2, P<0.05; 76.1+/-36.4, P = 0.05; 84.5+/-37.3, P<0.02; vs control 10.2+/-3.7).
      Incubation of non-inflamed non-IBD control tissue did not increase the IL-1ra/IL
      1beta ratio in any dilution compared to medium control (69.3+/-47.0, 54.1+/-30.6,
      79.4+/-34.0 vs control 76.1+/-37.3). Average percentage production of IL-1beta
      indexed against medium control was significantly less in UC after EF incubation
      as compared with CD (UC 24.0+/-4.8 vs CD 51.8+/-8.1; P<0.05). Average percentage
      production of IL-1ra was markedly higher in UC (135.9+/-3.4) than that in control
      patients (36.5+/-4.3) (P<0.0001). CONCLUSION: IBD tissues, after incubation with
      elemental diet modified in its fatty acid composition with fish oil, show an
      increase in IL-1ra/IL-1beta cytokine ratio. This effect of omega-3 fatty acid
      modulation is significantly more marked in UC compared with CD and is accompanied
      by both a reduction of IL-1beta and increase of IL-1ra. The positive direct anti
      inflammatory effect of elemental diet with fish oil in tissue affected with UC
      suggests dietary treatment of UC may be possible.

PMID- 16437719
TI  - Expression of triggering receptor on myeloid cell 1 and histocompatibility
      complex molecules in sepsis and major abdominal surgery.
AB  - AIM: To evaluate the surface expression of triggering receptor on myeloid cell 1
      (TREM-1), class II major histocompatibility complex molecules (HLA-DR), and the
      expression of the splicing variant (svTREM-1) of TREM-1 in septic patients and
      those subjected to major abdominal surgery. METHODS: Using flow cytometry, we
      examined the surface expression of TREM-1 and HLA-DR in peripheral blood
      monocytes from 11 septic patients, 7 elective gastrointestinal surgical patients,
      and 10 healthy volunteers. svTREM-1 levels were analyzed by RT-PCR. RESULTS:
      Basal expression of TREM-1 and HLA-DR in healthy volunteers was 35.91+/-14.75 MFI
      and 75.8+/-18.3%, respectively. In septic patients, TREM-1 expression was 59.9+/
      23.9 MFI and HLA-DR expression was 44.39+/-20.25%, with a significant difference
      between healthy and septic groups (P<0.05) for both molecules. In the surgical
      patients, TREM-1 and HLA-DR expressions were 56.8+/-20.85 MFI and 71+/-13.8%
      before surgery and 72.65+/-29.92 MFI and 72.82+/-22.55% after surgery. TREM-1
      expression was significantly different (P = 0.0087) between the samples before
      and after surgery and svTREM-1 expression was 0.8590+/-0.1451 MF1, 0.8820+/
      0.1460 MF1, and 2.210+/-0.7873 MF1 in the healthy, surgical (after surgery) and
      septic groups, respectively. There was a significant difference (P = 0.048) in
      svTREM-1 expression between the healthy and surgical groups and the septic group.
      CONCLUSION: TREM-1 expression is increased during systemic inflammatory
      conditions such as sepsis and the postoperative phase. Simultaneous low
      expression of HLA-DR molecules correlates with the severity of illness and
      increases susceptibility to infection. Additionally, TREM-1 expression is
      distinctly different in surgical patients at different stages of the inflammatory
      response before and after surgery. Thus, surface TREM-1 appears to be an
      endogenous signal during the course of the inflammatory response. svTREM-1
      expression is significantly increased during sepsis, appearing to be an indicator
      of severity of illness. Together, these data indicate that TREM-1 may play an
      important role in establishing and amplifying the systemic inflammatory response.
      TREM-1, HLA-DR, and svTREM-1 expression analysis can provide useful diagnostic
      and prognostic indicators during SIRS, CARS, and sepsis.

PMID- 16437720
TI  - Steatosis recovery after treatment with a balanced sunflower or olive oil-based
      diet: involvement of perisinusoidal stellate cells.
AB  - AIM: To analyze the relationship between perisinusoidal stellate cell (PSC)
      activation and the dietary fat quantity and composition in the treatment of
      hepatic steatosis. METHODS: Using an experimental rat model of steatosis based on
      the intake of a hyperlipidic diet (14% fat as olive oil or sunflower oil, HL-O
      and HL-S, respectively), we analyzed the liver's capability of recovery after the
      treatment with a normal-lipidic diet (5% fat as olive oil or sunflower oil, NL-O
      and NL-S, respectively) by immunocytochemical and Western blot analysis of glial
      fibrillary acidic protein (GFAP) expression in PSCs, collagen quantification and
      serum aminotransferase determination. RESULTS: The fatty infiltration in the
      steatotic livers decreased after the treatment with both NL diets, indicating
      liver recovery. This decrease was accompanied with a lower collagen deposition
      and aminotransferase level as well as changes in the PSC population that
      increased the GFAP expression. The above-mentioned effects were more pronounced
      in animals fed on NL-O based diet. CONCLUSION: Treatment with a balanced diet
      enriched in olive oil contributes to the liver recovery from a steatotic process.
      The PSC phenotype is a marker of this hepatic-recovery model.

PMID- 16437721
TI  - Prospective randomized comparison of oral sodium phosphate and polyethylene
      glycol lavage for colonoscopy preparation.
AB  - AIM: To compare the effectiveness, patient acceptability, and physical
      tolerability of two oral lavage solutions prior to colonoscopy in a Taiwanese
      population. METHODS: Eighty consecutive patients were randomized to receive
      either standard 4 L of polyethylene glycol (PEG) or 90 mL of sodium phosphate
      (NaP) in a split regimen of two 45 mL doses separated by 12 h, prior to
      colonoscopic evaluation. The primary endpoint was the percent of subjects who had
      completed the preparation. Secondary endpoints included colonic cleansing
      evaluated with an overall assessment and segmental evaluation, the tolerance and
      acceptability assessed by a self-administered structured questionnaire, and a
      safety profile such as any unexpected adverse events, electrolyte tests, physical
      exams, vital signs, and body weights. RESULTS: A significantly higher completion
      rate was found in the NaP group compared to the PEG group (84.2% vs 27.5%,
      P<0.001). The amount of fluid suctioned was significantly less in patients taking
      NaP vs PEG (50.13+/-54.8 cc vs 121.13+/-115.4 cc, P<0.001), even after
      controlling for completion of the oral solution (P = 0.031). The two groups
      showed a comparable overall assessment of bowel preparation with a rate of "good"
      or "excellent" in 78.9% of patients in the NaP group and 82.5% in PEG group (P =
      0.778). Patients taking NaP tended to have significantly better colonic segmental
      cleansing relative to stool amount observed in the descending (94.7% vs 70%, P =
      0.007) and transverse (94.6% vs 74.4%, P = 0.025) colon. Slightly more patients
      graded the taste of NaP as "good" or "very good" compared to the PEG patients
      (32.5% vs 12.5%; P = 0.059). Patients' willingness to take the same preparation
      in the future was 68.4% in the NaP compared to 75% in the PEG group (P = 0.617).
      There was a significant increase in serum sodium and a significant decrease in
      phosphate and chloride levels in NaP group on the day following the colonoscopy
      without any clinical sequelae. Prolonged (>24 h) hemodynamic changes were also
      observed in 20-35% subjects of either group. CONCLUSION: Both bowel cleansing
      agents proved to be similar in safety and effectiveness, while NaP appeared to be
      more cost-effective. After identifying and excluding patients with potential risk
      factors, sodium phosphate should become an alternative preparation for patients
      undergoing elective colonoscopy in the Taiwanese population.

PMID- 16437722
TI  - Health-related quality of life and impact of antiviral treatment in Chinese
      patients with chronic hepatitis C in Taiwan.
AB  - AIM: To evaluate health-related quality of life (HRQOL) in Chinese patients with
      chronic hepatitis C (CH-C), and the impact of antiviral treatment. METHODS: Short
      Form 36 (SF-36) Health-related Quality of Life Questionnaires to interview CH-C
      patients, and age- and sex-matched control subjects at outpatient clinics of a
      medical center in Taiwan were used. Data were transformed to scores for
      comparisons of eight major SF-36 domains. We also enrolled consecutive CH-C
      patients who completed one course of antiviral treatment (interferon alpha with
      ribavirin), and measured the HRQOL before, at the 12th wk of treatment, at the
      end of treatment, and at mo 6, after stopping the treatment to evaluate the
      impact of antiviral treatment. RESULTS: A total of 371 outpatients were enrolled,
      including 182 with CH-C and 189 age- and sex-matched subjects without CH-C. CH-C
      subjects had obviously lower educational status (P<0.01). Mean scores of domains
      in general health, physical functioning, role-physical, role-emotional, vitality,
      and mental health of the SF-36 were significantly lower in subjects with CH-C
      than those without CH-C (P<0.05). In an analysis of 47 CH-C patients who received
      and completed the whole course of antiviral treatment, mean scores of all domains
      were significantly lower at wk 12 of treatment compared to baseline. The scores
      returned to pretreatment values by the end of treatment, but were significantly
      increased at mo 6 after stopping the treatment. Among the 47 CH-C patients, 21
      had sustained responses and 26 had non-sustained responses to antiviral
      treatment. Compared to pretreatment values, subjects with sustained responses had
      significantly lower social functioning scores at wk 12 of treatment, and scores
      for all SF-36 domains returned to pretreatment values, and increased
      significantly at mo 6 after stopping the treatment. For non-sustained virological
      responders, scores of all SF-36 domains significantly decreased at wk 12 of
      treatment, and did not increase significantly by the end of treatment, or at mo 6
      after stopping the treatment when compared to the pretreatment values.
      CONCLUSION: HRQOL in CH-C patients is significantly impaired in most SF-36
      domains. Antiviral treatment impaired HRQOL of CH-C subjects during early
      treatment, mainly in non-sustained virological responders, and improved at mo 6
      after stopping the treatment, mainly in sustained virological responders.

PMID- 16437723
TI  - Bactericidal and anti-adhesive properties of culinary and medicinal plants
      against Helicobacter pylori.
AB  - AIM: To investigate the bactericidal and anti-adhesive properties of 25 plants
      against Helicobacter pylori (H. pylori). METHODS: Twenty-five plants were boiled
      in water to produce aqueous extracts that simulate the effect of cooking. The
      bactericidal activity of the extracts was assessed by a standard kill-curve with
      seven strains of H. pylori. The anti-adhesive property was assessed by the
      inhibition of binding of four strains of FITC-labeled H. pylori to stomach
      sections. RESULTS: Of all the plants tested, eight plants, including Bengal
      quince, nightshade, garlic, dill, black pepper, coriander, fenugreek and black
      tea, were found to have no bactericidal effect on any of the isolates. Columbo
      weed, long pepper, parsley, tarragon, nutmeg, yellow-berried nightshade,
      threadstem carpetweed, sage and cinnamon had bactericidal activities against H.
      pylori, but total inhibition of growth was not achieved in this study. Among the
      plants that killed H. pylori, turmeric was the most efficient, followed by cumin,
      ginger, chilli, borage, black caraway, oregano and liquorice. Moreover, extracts
      of turmeric, borage and parsley were able to inhibit the adhesion of H. pylori
      strains to the stomach sections. CONCLUSION: Several plants that were tested in
      our study had bactericidal and/or anti-adhesive effects on H. pylori. Ingestion
      of the plants with anti-adhesive properties could therefore provide a potent
      alternative therapy for H. pylori infection, which overcomes the problem of
      resistance associated with current antibiotic treatment.

PMID- 16437724
TI  - Learning curve of laparoscopy-assisted distal gastrectomy with systemic
      lymphadenectomy for early gastric cancer.
AB  - AIM: To evaluate the nature of the "learning curve" for laparoscopy-assisted
      distal gastrectomy (LADG) with systemic lymphadenectomy for early gastric cancer.
      METHODS: The data of 90 consecutive patients with early gastric cancer who
      underwent LADG with systemic lymphadenectomy between April 2003 and November 2004
      were reviewed. The 90 patients were divided into 9 sequential groups of 10 cases
      in each group and the average operative time of these 9 groups were determined.
      Other learning indicators, such as transfusion requirements, conversion rates to
      open surgery, postoperative complication, time to first flatus, and postoperative
      hospital stay, were evaluated. RESULTS: After the first 10 LADGs, the operative
      time reached its first plateau (230-240 min/operation) and then reached a second
      plateau (<200 min/operation) for the final 30 cases. Although a significant
      improvement in the operative time was noted after the first 50 cases, there were
      no significant differences in transfusion requirements, conversion rates to open
      surgery, postoperative complications, time to first flatus, or postoperative
      hospital stay between the groups. CONCLUSION: Based on operative time analysis,
      this study show that experience of 50 cases of LADG with systemic lymphadenectomy
      for early gastric cancer is required to achieve optimum proficiency.

PMID- 16437725
TI  - Baseline characterization of patients aged 70 years and above with hepatocellular
      carcinoma.
AB  - AIM: To characterize the baseline profiles of patients aged 70 years and above
      with hepatocellular carcinoma (HCC). METHODS: A series of 127 consecutive
      patients with HCC were enrolled between 2000 and 2004, and none of them had been
      diagnosed as having HCC previously. Baseline profiles, including parameters of
      hepatic function such as serum transaminase and prothrombin time [PT (%
      activity)] were compared between patients aged > or = 70 and < 70 years. RESULTS:
      Patients > or = 70 years old showed significantly lower levels of aspartate
      aminotransferase (P = 0.04) and alanine aminotransferase (P = 0.01), and
      significantly higher PTs (P = 0.04) and platelet counts (P = 0.02).
      Concomitantly, among > or = 70-year-old patients, HCC was more common in non
      cirrhotics, whereas among patients < 70 years old, HCC was more common in
      cirrhotics. There was no significant difference between the groups in the number
      or size of tumors. CONCLUSION: Older HCC patients showed less inflammation and
      better preservation of hepatic function, indicating that not only cirrhotic
      patients but also non-cirrhotic patients should be considered as a high-risk
      group among the elderly.

PMID- 16437726
TI  - CT-maximum intensity projection is a clinically useful modality for the detection
      of gastric varices.
AB  - AIM: To evaluate the efficacy of CT-maximum intensity projection (CT-MIP) in the
      detection of gastric varices and their inflowing and outflowing vessels in
      patients with gastric varices scheduled to undergo balloon-occluded retrograde
      transvenous obliteration (B-RTO). METHODS: Sixteen patients with endoscopically
      confirmed gastric varices were included in this study. All patients were
      evaluated with CT-MIP using three-dimensional reconstructions, before and after B
      RTO. RESULTS: CT-MIP clearly depicted gastric varices in 16 patients (100%), the
      left gastric vein in 6 (32.5%), the posterior gastric vein in 12 (75.0%), the
      short gastric veins in 13 (81.3%), gastrorenal shunts in 16 (100%), the
      hemiazygos vein (HAZV) in 4 (25.0%), the pericardiophrenic vein (PCPV) in 9
      (56.3%), and the left inferior phrenic vein in 9 patients (56.3%). Although flow
      direction itself cannot be determined from CT-MIP, this modality provided clear
      images of the inflowing and the outflowing vessels. Moreover, in one patient,
      short gastric veins were not seen on conventional angiographic portography images
      of the spleen, but were clearly revealed on CT-MIP. CONCLUSION: We suggest that
      CT-MIP should be considered as a routine method for detecting and diagnosing
      collateral veins in patients with gastric varices scheduled for B-RTO.
      Furthermore, CT-MIP is more useful than endoscopy in verifying the early
      therapeutic effects of B-RTO.

PMID- 16437727
TI  - Effect of Clostridium butyricum on fecal flora in Helicobacter pylori eradication
      therapy.
AB  - AIM: To investigate the effect of probiotic bacterium, Clostridium butyricum
      MIYAIRI 588 strain (CBM) on the changes of the fecal flora in Helicobacter pylori
      (H. pylori) treatment. METHODS: Thirty-five patients with gastric or duodenal
      ulcers positive for H. pylori were randomized either to 1 wk amoxicillin,
      clarithromycin, lansoprazole (Group 1) or to the same regimen supplemented with
      CBM 7 d ahead of the triple therapy (Group 2). Stool samples were collected
      before and 2, 4, 7, 15, and 22 d after the starting eradication therapy, and were
      examined intestinal flora. Patients were required to keep a diary record of their
      condition. RESULTS: Obligate anaerobes decreased significantly on d 2, 4, 8 and
      15 in Group 1. On the other hand, they did not decrease significantly in Group 2.
      The Escherichia coli was dominant bacterium in Enterobacteriaceae, but that was
      replaced by other species such as Klebsiella and Enterobacter after eradication
      in Group 1. The change was suppressed in Group 2. Abdominal symptoms were less
      frequent in Group 2 than in Group 1. CONCLUSION: The combined use of CBM reduced
      the changes in the intestinal flora and decreased the incidence of
      gastrointestinal side effects.

PMID- 16437728
TI  - Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients
      with Crohn's disease.
AB  - AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients
      with Crohn's disease (CD). METHODS: A total of 120 patients with CD, 85 patients
      with UC, and 100 unrelated healthy controls were genotyped. Genotyping was
      performed by allele-specific PCR or by PCR-RFLP analysis. RESULTS: Our results
      showed that the 1672T and -207C alleles were obviously over-represented in CD
      patients only (P<0.01 and P<0.05, respectively) compared to the control
      population. The G113A polymorphism was completely absent in our studied
      population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD
      patients as compared with controls. Additionally, the frequency of the TC
      haplotype was increased in patients with ileocolitis or colitis, and was mainly
      associated with the fibrostenotic phenotype of the disease. Furthermore, when the
      TC haplotype was compared jointly with the carriage of at least one mutation of
      the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC,
      compared to controls. Regarding the location of the disease, the concomitant
      presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with
      ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the
      1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent
      risk factors for CD in the Greek population.

PMID- 16437729
TI  - Bleeding gastric varices: results of endoscopic injection with cyanoacrylate at
      King Chulalongkorn Memorial Hospital.
AB  - AIM: To evaluate the efficacy and safety of gastric varices injection with
      cyanoacrylate in patients with gastric variceal bleeding. METHODS: Twenty-four
      patients (15 males, 9 females) with gastric variceal bleeding underwent
      endoscopic treatment with cyanoacrylate injection. Successful hemostasis,
      rebleeding rate, and complications were retrospectively reviewed. Followed up
      endoscopy was performed and repeat cyanoacrylate injection was given until
      gastric varices were obliterated. RESULTS: Seventeen patients achieved definite
      hemostasis. Of these, 14 patients had primary success after initial endoscopic
      therapy. Ten patients developed recurrent bleeding. Repeated cyanoacrylate
      injection stopped rebleeding in three patients. Transjugular intrahepatic
      portosystemic shunt (TIPS) was performed to control rebleeding in one patient
      which occurred after repeat endoscopic therapy. Six patients died (three from
      uncontrolled bleeding, two from sepsis, and one from mesenteric vein thrombosis).
      Minor complications occurred in 11 patients (six epigastric discomfort and five
      post injection ulcers). Cyanoacrylate embolism developed in two patients. One of
      these patients died from mesenteric vein thrombosis. The other had pulmonary
      embolism which resolved spontaneously. Advanced cirrhosis and hepatocellular
      carcinoma (HCC) were major risk factors for uncontrolled bleeding. CONCLUSION:
      Endoscopic treatment for bleeding gastric varices with cyanoacrylate injection is
      effective for immediate hemostasis. Repeat cyanoacrylate injection has a lower
      success rate than the initial injection. Cyanoacrylate embolism is not a common
      serious complication.

PMID- 16437730
TI  - Apoptosis mechanisms of human gastric cancer cell line MKN-45 infected with human
      mutant p27.
AB  - AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of
      the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS:
      The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric
      cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment
      analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric
      cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection
      efficiency reached 100%. After 18 h of infection, we observed an apoptotic
      hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic
      bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was
      significantly higher in the Ad-p27mt group (89.4+/-3.12%) compared to the control
      group (3.12+/-0.13%, P < 0.01). CONCLUSION: Human mutant p27 can induce apoptosis
      of the human gastric cancer cells in vitro.

PMID- 16437731
TI  - Is colonoscopy sufficient for colorectal cancer surveillance in all HNPCC
      patients?
AB  - A 34-year-old male with hereditary non-polyposis colon cancer with a mutation in
      hMSH2 line is reported. Despite regular colonoscopic follow-up, he developed
      cecal cancer involving the extraluminal area. Due to sub-occlusive symptoms, the
      patient was submitted to further colonoscopy, however with no clear evidence of
      neoplasia. Thin slice multiplanar reconstruction computed tomography CT scan
      performed thereafter revealed a transmural mass 2.5 cm in size localized near the
      cecal valve. Discussion is made on the reliability of colonoscopic examinations
      as well as the need for further investigations in the follow-up of patients at
      very high risk of right-sided colon cancer, such as male hMSH2 carrier affected
      by hereditary non-polyposis colon cancer.

PMID- 16437732
TI  - Remission of bronchial asthma after viral clearance in chronic hepatitis C.
AB  - A 53-year-old man with a history of blood transfusion at the age of 20 was
      admitted to our hospital because of liver dysfunction. He had bronchial asthma
      when he was 18 years old, which naturally resolved within 2 years. However, his
      bronchial asthma recurred at the age of 45 and was treated with oral
      theophylline. He was diagnosed as having chronic hepatitis C based on the
      histological and clinical findings, and then interferon (IFN) therapy was
      administered. The frequency of bronchial asthma attack was gradually decreasing
      after IFN therapy with marked improvement of hypereosinophilia. He achieved
      sustained viral response (SVR) and his bronchial asthma did not worsen even after
      the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were
      considered in the remission of asthma in this case. HCV infection could be the
      cause of bronchial asthma, especially in patients with late appearance of asthma.

PMID- 16437733
TI  - Concordance of ulcerative colitis in monozygotic twin sisters.
AB  - The etiology of inflammatory bowel disease is multifactorial and appears to
      combine both genetic and environmental factors. We experienced here a rare
      occurrence of woman monozygotic twins with ulcerative colitis (UC). A 45-year-old
      woman (the elder monozygotic twin) was admitted to our hospital because of bloody
      diarrhea occurring over 10 times per day, abdominal pain and fever. She was
      diagnosed as UC at the age of 22, and repeated the relapse and remission. She was
      diagnosed as relapse of UC and total colitis type. Her younger monozygotic twin
      sister also suffered from UC at the age of 22. Human leukocyte antigen was
      examined serologically with DNA type in both patients. DRB1*1502, which was
      previously shown to be dominant in Japanese patients with UC, was not observed in
      this case. Although the concordance in monozygotic twin in UC is reported to be
      6.3-18.8%, the concordant case like this is relatively rare. We report this rare
      case of UC and the previously reported cases are also discussed.

PMID- 16437734
TI  - Changes in serum leptin and beta endorphin levels with weight loss by
      electroacupuncture and diet restriction in obesity treatment.
AB  - This study aims to investigate the role of changes in leptin and beta endorphin
      (BE) levels in weight loss following electroacupuncture (EA) application in
      obesity treatment. EA was applied to 20 females who were 41.45 +/- 4.71 years old
      and had a body mass index of 36.00 +/- 2.66; and a diet program was applied to 20
      females who were 42.30 +/- 4.35 years old and had a body mass index of 34.90 +/-
      3.21. There was a 4.5% weight reduction in the patients with EA application,
      whereas patients on diet restriction had a 3.1% weight reduction. A decrease of
      loss of body weight was observed in the EA group (p < 0.000) when compared
      against the diet restricted group. A decrease of serum leptin levels (p < 0.000)
      and an increase in the serum BE (p < 0.05) levels were observed in the EA group
      compared to the diet restricted group. In this study, reduced serum leptin levels
      paralleling to weight loss were observed in the EA group. Furthermore, it is
      thought that in the EA applied group, increasing serum BE level probably enhanced
      the lipolitic activity which may have caused weight loss in obese people by
      mobilizing energy stores. It may be considered that the EA application with diet
      restriction in obesity treatment is more effective than the diet restriction
      alone.

PMID- 16437735
TI  - Immunomodulatory effects of a traditional Chinese medicine with potential
      antiviral activity: a self-control study.
AB  - Traditional Chinese medicine (TCM) has been used for prevention and treatment of
      severe acute respiratory syndrome (SARS) in Hong Kong during the outbreak in
      spring 2003. We investigated the immunomodulating effects of an innovative TCM
      regimen derived from two herbal formulas (Sang Ju Yin and Yu Ping Feng San) for
      treating febrile diseases. Thirty-seven healthy volunteers were given the oral
      TCM regimen daily for 14 days. Peripheral venous blood samples were taken on days
      0, 15 and 29 for hematology, biochemistry and immunology tests, including the
      measurement of blood lymphocyte subsets and plasma T-helper lymphocyte types 1
      and 2 cytokines and receptor. After 3 months, 23 of the volunteers participated
      in a control study without TCM treatment for the same time course of blood tests.
      Two volunteers withdrew on day 2, due to headache and dizziness. All others
      remained well without any side effects. No participants showed significant
      changes in their blood test results, except that the T-lymphocyte CD4/CD8 ratio
      increased significantly from 1.31 +/- 0.50 (mean +/- SD) on day 0 to 1.41 +/-
      0.63 on day 15 (p < 0.02), and reduced to 1.32 +/- 0.47 on day 29 (p < 0.05). In
      the control study, there were no changes in the CD4/CD8 ratio. The transient
      increase in CD4/CD8 ratio was likely due to the TCM intake. We postulate that the
      administration of the innovative TCM may have beneficial immunomodulatory effects
      for preventing viral infections including SARS.

PMID- 16437736
TI  - Effects of electrical acupuncture on acupoint BL15 evaluated in terms of heart
      rate variability, pulse rate variability and skin conductance response.
AB  - In this research, heart rate variability (HRV), pulse rate variability (PRV) and
      human skin conductance (SC) of all acupoints on Heart Meridian were used to
      evaluate the effects of electrical acupuncture (EA) on acupoint BL15 (Bladder
      Meridian). Ten healthy volunteers (aged 23 +/- 6) were selected as the control
      group on the first day, and then used again as the experimental group on the
      second day. The control group received sham EA during the study, while subjects
      of the experimental group were stimulated by 2 Hz EA on acupoint BL15 for 10
      minutes. Electrocardiogram (ECG), wrist blood pressure pulse meter and skin
      conductance response (SCR) device were used to measure and analyze HRV, PRV and
      SCR for the two groups before and after stimulation. From the spectrum analysis
      of ECG and pulse pressure graph, we found that the EA applied on BL15 could
      induce a significant increase in the normalized high frequency power (nHFP)
      component of HRV and PRV, as well as a significant decrease in the normalized low
      frequency power (nLFP) part (p < 0.05). Moreover, both the heart rate and pulse
      rate were reduced in the analysis of the time domain of ECG and PRV. Furthermore,
      most of the SCR values at acupoints were decreased after stimulation. These
      results also indicate that the stimulation of BL15 by EA could cause relaxation,
      calmness and reduce feeling of tension or distress.

PMID- 16437737
TI  - Effects of chan-chuang qigong on improving symptom and psychological distress in
      chemotherapy patients.
AB  - The purpose of this study was to explore the effect of Chan-Chuang qigong on
      symptoms distress and psychological distress of breast cancer patients who
      underwent chemotherapy. A quasi-experimental design was adopted. Subjects were
      recruited from breast cancer outpatients receiving chemotherapy at an 1800-bed
      medical center in Taipei, Taiwan. Of these subjects, 35 were assigned to the
      control group and 32 to the experimental group in which Chan-Chuang qigong was
      administered. Assignment was not random. The instruments included a 21-item
      symptom distress scale and psychological distress with the symptom checklist-90
      revised. Data of the symptoms and psychological distress were collected on the
      day before chemotherapy as baseline values, and also collected on days 8, 15 and
      22 of chemotherapy. The results showed that the overall severity of symptom
      distress in the experimental group was significantly lower than the control group
      on day 22 (p < 0.05). The symptoms with significant improvement included pain,
      numbness, heartburn and dizziness (p < 0.05). With regard to psychological
      distress, the difference of overall severity between the two groups was not
      statistically significant (p > 0.05). However, the items of "unwillingness to
      live" (p < 0.05) and "hopelessness about the future" (p < 0.05) were
      significantly improved in the experimental group. In conclusion, Chan-Chuang
      qigong had the effect of attenuating the symptom distress and probably some part
      of the psychological distress of chemotherapy patients.

PMID- 16437738
TI  - The different immunomodulation of indirect moxibustion on normal subjects and
      patients with systemic lupus erythematosus.
AB  - Moxibustion has been thought to enhance immunity in healthy condition, but
      suppress abnormal immune response in disease status. We collected 12 patients
      with systemic lupus erythematosus (SLE) and 12 healthy women who received
      indirect moxibustion on acupuncture points ST-36 (Zusanli) and SP-6 (Sanyinjiao)
      20 minutes per day for 1 week. During the course, there were no changes of their
      regular medications or intercurrent infections in normal subjects and SLE
      patients. We found that indirect moxibustion for 1 week could elevate CD3+ and
      CD4+ T-lymphocytes in normal subjects, whereas decrease relative proportions of
      CD8+ T-lymphocytes in patients with SLE. This result confirms that indirect
      moxibustion has different immunomodulation in normal condition and autoimmune
      status. However, whether immunomodulatory effects of indirect moxibustion are
      beneficial for normal subjects and patients with SLE require further
      confirmation.

PMID- 16437739
TI  - Moxibustion at ST36 alleviates pain in complete Freund's adjuvant-induced
      arthritic rats.
AB  - This study was to investigate the antinociceptive effects of moxibustion in a
      complete Freund's adjuvant (CFA)-induced arthritic rat model, and the effects of
      moxibustion on immunohistochemical changes at the spinal cord level. Moxibustion
      was applied to the ipsilateral (right) Zusanli (ST36) acupoint to the lesion side
      for 9 days to CFA-induced arthritic rats. The stepping force was measured as a
      behavioral test, c-Fos immunohistochemistry, NO production and nNOS Western blots
      were examined to evaluate antinociceptive effects. Moxibustion at ST36
      significantly improved the stepping force in the affected hind limb in CFA
      induced arthritis. Moreover, moxibustion at ST36 suppressed the production of NO
      and the protein expression of c-Fos and nNOS induced by arthritis. These results
      suggest that moxibustion at ST36 has a potent antinociceptive effect in an
      arthritic rat model, and modulates neuronal excitability and endogenous NO
      production by suppressing c-Fos and nNOS protein expression.

PMID- 16437740
TI  - The comparison on changes of the body heats in electroacupuncture analgesia and
      anesthesia by ketamine hydrochloride in dogs.
AB  - This study was performed to clarify the differences of the body heats between
      electroacupuncture analgesia (EA) and anesthesia by ketamine hydrochloride
      (ketamine anesthesia) in dogs. Nine clinically healthy dogs were divided into
      ketamine anesthesia (control: 5 heads) and EA (experimental: 4 heads) groups,
      respectively. The acupoints GV-5 and Bai-Hui were used. The infrared
      thermographic system was used to determine the body heats. The body heats was
      determined at areas such as the dorsocranial (DCr), dorsocaudal (DCd),
      ventrocranial (VCr) and ventrocaudal (VCd) regions, on pretreatment, 10, 20, 30,
      50 and 90 minutes after treatments, respectively in control and experimental
      groups. The body heats showed decreasing tendency until 30 minutes after ketamine
      injection, and then showed increasing pattern until 90 minutes after at all areas
      investigated in the control group. However, no significant differences of the
      body heats in the DCr, DCd, VCr and VCd regions were found in the control group.
      On the other hand, the body heats showed increasing tendency until 30 minutes,
      and then showed decreasing pattern until 90 minutes after EA, in the experimental
      group. The significant difference was observed at 30 minutes in the DCr region,
      and also at 10, 20 and 30 minutes in the DCd regions in the experimental group (p
      < 0.05). The significant differences of the body heats were detected at 20
      minutes in the DCr region, at 30 minutes in the DCd region and at 30 minutes in
      the VCd region between the experimental and control groups (p < 0.05). In
      conclusion, EA increases of the body heat in the contrary to that of ketamine
      anesthesia.

PMID- 16437741
TI  - Effect and mechanism of total saponin of Dioscorea on animal experimental
      hyperuricemia.
AB  - In this study, we investigated the effects and mechanisms of Total Saponin of
      Dioscorea (TSD) on animal experimental hyperuricemia. Mouse and rat hyperuricemic
      models were made by orally administering yeast extract paste once a day (30 and
      20 g/kg, respectively), for 7 days. Yeast would disturb normal purine metabolism
      by increasing xanthine oxidase (XOD) activity and generating large quantities of
      uric acid. This model is similar to human hyperuricemia, which is induced by high
      protein diets, due to a purine and nucleic acid metabolic disturbance. Another
      mouse hyperuricemia model was generated by intraperitoneal injection once with
      uric acid 250 mg/kg or potassium oxonate 300 mg/kg. Potassium oxonate, a urate
      oxidase inhibitor, can raise the serum uric acid level by inhibiting the
      decomposition of uric acid. Likewise, injecting uric acid can also increase serum
      uric acid concentration. The concentration of uric acid in serum or urine was
      detected by the phosphotungstic acid method, and the activity of XOD was assayed
      by a test kit. The results showed that TSD (240, 120 and 60 mg/kg, ig) could
      significantly lower the level of serum uric acid in hyperuricemic mice. TSD (120
      and 60 mg/kg, ig) could also lower the level of serum uric acid in hyperuricemic
      rats, reduce the activity of XOD in the serum and liver of hyperuricemic rats,
      and increase the level of urine uric acid concentration as well as 24-hour total
      uric acid excretion. In conclusion, TSD possesses a potent anti-hyperuricemic
      effect on hyperuricemic animals, and the mechanism may be relevant in
      accelerating the excretion and decreasing the production of uric acid.

PMID- 16437742
TI  - Physiological function of insoluble dietary fiber prepared from exploded oak wood
      (Quercus mongolica).
AB  - This study investigated the production of insoluble dietary fiber using exploded
      and chemically treated oak wood (Quercus mongolica) and the physiological
      functions of prepared insoluble dietary fiber in laboratory animals. To produce
      high quality insoluble dietary fiber, the steam explosion treatment was performed
      at 25 kgf/cm2 pressure for 6 minutes. In the chemical analysis of insoluble
      dietary fiber, exploded oak wood was pretreated by 1% sodium hydroxide solution.
      The insoluble dietary fiber contained 7.6% residual lignin and 61.7% of alpha
      cellulose. In order to compare the physiological functions of prepared insoluble
      dietary fiber with those of commercial insoluble dietary fiber, Sprague-Dawley
      male rats weighing 100 +/- 10 g were randomly assigned to one normal diet and
      five high cholesterol diets, containing 1% cholesterol. The high cholesterol diet
      groups were classified as the fiber-free diet (FF group), 5% commercial alpha
      cellulose diet group (5C group), 10% commercial alpha-cellulose group (10C
      group), 5% insoluble dietary fiber group (5M group) and 10% insoluble dietary
      fiber group (10M group). Food intake, weight gain and food efficiency ratio in
      high cholesterol groups were significantly higher than those of the normal group,
      but there were no significant differences among the high cholesterol diet groups.
      In addition, there were no significant differences in the weights of liver,
      kidney and small intestine in insoluble dietary fiber-supplemented groups. Cecum
      weights in all insoluble dietary fiber groups were significantly higher than
      those of the FF group. There were no significant differences in the activities of
      the glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase
      (GOT) among the insoluble dietary fiber-supplemented groups. In conclusion, the
      prepared insoluble dietary fiber and the commercially available insoluble fiber
      showed the same physiological effects. Moreover, the preparation method for the
      insoluble dietary fiber from the exploded oak wood was successful.

PMID- 16437743
TI  - Therapeutic effects and molecular mechanisms of Ginkgo biloba extract on liver
      fibrosis in rats.
AB  - Oxidative stress can be implicated as a cause of liver fibrosis. In this sense,
      Ginkgo Biloba Extract (EGB), an antioxidant, may be beneficial in restraining
      liver fibrosis. The aim of this study was to evaluate the effects of EGB on
      experimental liver fibrosis. Rat liver fibrosis was induced by intraperitoneal
      injection of carbon tetrachloride (CCl4) twice a week for 8 weeks. Three groups
      of rats received EGB (0.25, 0.5 and 1.0 g/kg, respectively) by stomach everyday.
      CCl4 administration induced liver fibrosis, which was inhibited by EGB in a dose
      dependent manner. The histopathologic score of fibrosis, liver function and the
      levels of plasma hyaluronic acid (HA) and laminin (LN) were significantly
      improved in rats treated with CCl4 + EGB, compared with those treated with CCl4
      only (p < 0.01 or p < 0.05). The activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) were notably elevated, while malondialdehyde
      (MDA) content was significantly decreased in the rats treated with CCl4 + EGB (p
      < 0.01 or p < 0.05). Inhibition of hepatic stellate cell (HSC) activation and
      nuclear factor kappaBP65 (NF-kappaBP65) expression was demonstrated in the livers
      of EGB-treated rats. The activation of NF-kappaB was significantly suppressed in
      EGB-treated rats determined by electrophoretic mobility shift assay (EMSA).
      Furthermore, EGB reduced expressions of transforming growth factor-beta1 (TGF
      beta1) and collagen I mRNA. In conclusion, EGB is able to ameliorate liver injury
      and prevent rats from CCl4-induced liver fibrosis by suppressing oxidative
      stress. This process may be related to inhibiting the induction of NF-kappaB on
      HSC activation and the expression of TGF-beta1.

PMID- 16437744
TI  - Effect of Polygala tenuifolia root extract on cerebral ischemia and reperfusion.
AB  - In this study, the effects of Polygala tenuifolia root extract on brain
      ischemia/reperfusion injury in Mongolian gerbils were investigated. The gerbils
      were administered ethanol extract of P. tenuifolia and its four sub-fractions
      orally 2 hours prior to ischemia, and were subjected to a 20-minute no-flow
      cerebral ischemia in vivo. Thirty minutes and 72 hours after reperfusion, the
      brain was removed and the ATP, lactate and lipid peroxide levels were determined,
      and the neurons in the hippocampal CA1 subfield were examined. In the vehicle
      treated ischemic gerbils, the brain ATP levels decreased significantly, but this
      decrease was prevented by pre-treatment with an n-butanol fraction of P.
      tenuifolia. In contrast, both the lactate content and lipid peroxidation levels
      were elevated in the vehicle-treated ischemic animals, but this elevation was
      inhibited by ethanol extract and n-butanol fraction of P. tenuifolia,
      respectively. Both the ethanol extract and n-butanol fraction of P. tenuifolia
      attenuated post-ischemic neuronal necrosis in the hippocampal CA1 subfield. Our
      findings suggest that both ethanol extract and n-butanol fraction of P.
      tenuifolia root can reduce brain damage during ischemia and reperfusion, and
      prevent lipid peroxidation and preserve the energy metabolism.

PMID- 16437745
TI  - Antiproliferative and apoptotic effects of tetrandrine on different human
      hepatoma cell lines.
AB  - Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root
      of Hang-Fang-Chi (Stephania tetrandra S. Moore), is well known to possess
      activities including antioxidant, anti-inflammation, anti-fibrotic and
      anticancer. It is used clinically to treat hypertension and silicosis. In the
      present study, the anti-proliferative and apoptotic effects of TET were evaluated
      on three different hepatoma cell lines, namely Hep G2, PLC/PRF/5 and Hep 3B.
      Using XTT assay, results showed that the IC50 values of TET were 4.35 microM for
      Hep G2, 9.44 microM for PLC/PRF/5 and 10.41 microM for Hep 3B cells. The CC50 of
      TET against BNL-CL.2 mouse normal liver cells was 31.12 microM. Interestingly,
      TET exhibited a lower IC50 value and better selectivity against Hep G2 and
      PLC/PRF/5 cells than cisplatin. Microscopic observation study, DNA fragmentation
      assay and flow cytometric analysis further supported apoptotic effect of TET on
      both PLC/PRF/5 and Hep 3B cells. The cell cycle of PLC/PRF/5 treated with TET
      appeared to arrest at G2/M phase in a dose-dependent manner, whereas no effect
      was noted on the cell cycle of Hep 3B cells. The present study concludes that TET
      exhibited anti-proliferative effect on Hep G2, PLC/PRF/5 and Hep 3B cells in a
      dose-dependent manner. TET also possesses a lower IC50 and better SI value than
      cisplatin against Hep G2 and PLC/PRF/5 cells. The effect of TET on cell cycle
      progression was found to vary with the type of hepatoma cells, suggesting the
      genetic make-up of the cells play an important role in the response to drug
      treatment.

PMID- 16437746
TI  - Effects of ginseng on the proliferation of human lung fibroblasts.
AB  - In this study, we investigated the effects of methanolic extracts of white
      ginseng (Panax ginseng C.A. MEYER) and two kinds of heat-treated ginseng made by
      steaming fresh ginseng at 100 degrees C for 3 hours (HTG-100) or 120 degrees C
      for 3 hours (HTG-120) on the cell growth of human fibroblasts. All of the tested
      ginseng extracts stimulated cell growth, although the effect of HTG-120 was
      weaker than that of the other extracts. However, none of the ginseng extracts
      exhibited any effect on the growth of old cells with a population doubling level
      (PDL) of 48.7. Flow cytometric analysis showed that ginseng extracts raised the
      population of cells in G0/G1 phase after treatment for 24 hours, but did not
      exert any effect after treatment for 48 hours. These results suggest that
      ginsengs exert their cell growth-promoting action mainly on younger cells at an
      early stage of the cell cycle, and that this effect is closely associated with an
      increase in the population of cells in the G0/G1 phase.

PMID- 16437747
TI  - Inhibitory effects of anti-SARS traditional Chinese medicines on the UV
      irradiation of lambda-lysogen.
AB  - By using lambda-lysogen as a model, the inhibitory effects of anti-severe acute
      respiratory syndrome (SARS) traditional Chinese medicines (TCMs) prescription I
      on the UV irradiation were investigated in this present study. It was found that
      the prescription I possessed obvious inhibitory effects on the UV induction of
      lambda-lysogen, the inhibitory rate reaching 83.87%. Among five medicinal herbs
      prescribed in that formula, Herba Patriniae, Radix Astragali and Radix
      Glycyrrhizae played important roles. When these three herbs were eliminated from
      the recipe separately, the inhibitory effects were prominently decreased. If only
      one of these five medicinal herbs was added into the medium of lambda-lysogen,
      the inhibitory rates ranged from 27.0% approximately 45.0%. By electron spin
      resonance (ESR) detection, we found that the prescription I, Herba Patriniae and
      other main herbs in that recipe, could quench effectively the free radicals
      generated in the process of lambda-lysogenic cells by UV. These results provide a
      novel idea for further studying the pharmacology of TCM and exploring the
      mechanism of SARS virus infection.

PMID- 16437749
TI  - Sleep deprivation: a link to obesity?

PMID- 16437750
TI  - How long is a cold contagious? Is there any way to prevent transmitting a cold?

PMID- 16437748
TI  - Macrophage-mediated inhibitory effect of Zingiber officinale Rosc, a traditional
      oriental herbal medicine, on the growth of influenza A/Aichi/2/68 virus.
AB  - The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional
      herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was
      investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR
      (0.1 approximately 100 microg/ml) to the infected cells did not have any
      inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW
      cells, a murine macrophage (Mphi) cell line, exhibited an apparent inhibitory
      effect on MDCK cells without cytotoxicity. In accordance with the time-dependent
      inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor
      (TNF)-alpha was gradually accumulated in ZOR-CM by the induction of TNF-alpha
      mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of
      ZOR-CM was reduced significantly by the removal of TNF-alpha after the formation
      of an immune complex with anti-TNF-alpha monoclonal antibody. These data
      suggested that ZOR itself has no inhibitory effect on the growth of influenza
      virus, but could exert its effect via macrophage activation leading to production
      of TNF-alpha.

PMID- 16437751
TI  - On call. I have always had my blood tests taken the first thing in the morning,
      before I've had breakfast. We've just moved to a new home and I'll have a long
      commute to the hospital, so I'd like to eat before I start out. My cholesterol
      has always been great, so my doctor said a light breakfast won't interfere with
      cholesterol tests. But he didn't know if eating would change my PSA result. What
      do you think?

PMID- 16437752
TI  - A view from Bucharest.

PMID- 16437753
TI  - Therapeutic decision making in MS: impact of a slower disability progression.

PMID- 16437754
TI  - Bibliography. Current world literature. Neuromuscular diseases: nerve.

PMID- 16437756
TI  - Cancer-associated malnutrition: an introduction.
AB  - Cancer is a major cause of morbidity and mortality throughout the world. It is
      the second most frequent cause of death in Europe and is becoming the leading
      cause of death in old age. Patients with cancer will develop a large number of
      physical symptoms. Malnutrition and weight loss are common and are due to a
      variety of mechanisms involving the tumour, the host response to the tumour, and
      anticancer therapies. Inadequate intake of energy and nutrients alone is unable
      to account for the substantial changes in nutritional status seen in patients
      with cancer. In advanced cancer, cachexia often occurs. This complex
      multifactorial syndrome is associated with metabolic abnormalities, anorexia,
      early satiety and reduced food intake, depletion of lean body mass, muscle
      weakness, oedema, fatigue, impaired immune function, and declines in attention
      span and concentration. The development and implementation of screening and
      assessment tools is essential for effective nutritional intervention and
      management of patients with cancer. Proactive nutritional interventions should
      ideally form an integral part of cancer therapy, with the aim of improving
      clinical outcomes and quality of life. This supplement brings together a
      collection of papers discussing various topics regarding nutrition in cancer.

PMID- 16437757
TI  - Cancer-associated malnutrition.
AB  - Malnutrition is a common problem among patients with cancer, affecting up to 85%
      of patients with certain cancers (e.g. pancreas). In severe cases, malnutrition
      can progress to cachexia, a specific form of malnutrition characterised by loss
      of lean body mass, muscle wasting, and impaired immune, physical and mental
      function. Cancer cachexia is also associated with poor response to therapy,
      increased susceptibility to treatment-related adverse events, as well as poor
      outcome and quality of life. Cancer cachexia is a complex, multifactorial
      syndrome, which is thought to result from the actions of both host- and tumour
      derived factors, including cytokines involved in a systemic inflammatory response
      to the tumour. Early intervention with nutritional supplementation has been shown
      to halt malnutrition, and may improve outcome in some patients. However,
      increasing nutritional intake is insufficient to prevent the development of
      cachexia, reflecting the complex pathogenesis of this condition. Nutritional
      supplements containing anti-inflammatory agents, for example the polyunsaturated
      fatty acid (PUFA) eicosapentanoic acid (EPA), have been shown to be more
      beneficial to malnourished patients than nutritional supplementation alone. EPA
      has been shown to interfere with multiple mechanisms implicated in the
      pathogenesis of cancer cachexia, and in clinical studies, has been associated
      with reversal of cachexia and improved survival.

PMID- 16437758
TI  - The causes and consequences of cancer-associated malnutrition.
AB  - Cancer-associated malnutrition can result from local effects of a tumour, the
      host response to the tumour and anticancer therapies. Although cancer patients
      often have reduced food intake (due to systemic effects of the disease, local
      tumour effects, psychological effects or adverse effects of treatment),
      alterations in nutrient metabolism and resting energy expenditure (REE) may also
      contribute to nutritional status. Several agents produced by the tumour directly,
      or systemically in response to the tumour, such as pro-inflammatory cytokines and
      hormones, have been implicated in the pathogenesis of malnutrition and cachexia.
      The consequences of malnutrition include impairment of immune functions,
      performance status, muscle function, and quality of life. In addition, responses
      to chemotherapy are decreased, chemotherapy-induced toxicity and complications
      are more frequent and severe, and survival times are shortened. Depression,
      fatigue and malaise also significantly impact on patient well-being. In addition,
      cancer-related malnutrition is associated with significant healthcare-related
      costs. Nutritional support, addressing the specific needs of this patient group,
      is required to help improve prognosis, and reduce the consequences of cancer
      associated nutritional decline.

PMID- 16437759
TI  - Nutritional screening and assessment in cancer-associated malnutrition.
AB  - Up to 85% of all patients with cancer develop clinical malnutrition, which
      negatively affects patients' response to therapy, increases the incidence of
      treatment-related side effects and can decrease survival. Early identification of
      patients who are malnourished or at risk of malnutrition can promote recovery and
      improve prognosis. In addition, early nutritional intervention is cost effective,
      as it reduces complication rates and length of hospital stay. The development and
      use of screening and assessment tools is essential for effective nutritional
      intervention and management of patients with cancer. Nutritional screening aims
      to identify patients who are malnourished or at significant risk of malnutrition.
      Patients identified through screening require referral to a dietician or
      specialist in nutrition for an in-depth nutritional assessment, involving
      examination of medical, dietary, psychological and social history, physical
      examination, anthropometry and biochemical testing. Interventions initiated after
      nutritional assessment should be tailored to the individual and take into
      consideration the patient's prognosis. Nutritional care is a fundamental aspect
      of nursing practice and nurses are ideally placed to play an essential role in
      the early detection and screening of malnutrition in patients with cancer.

PMID- 16437760
TI  - Nutritional support strategies for malnourished cancer patients.
AB  - A large body of evidence exists, which demonstrates the importance of nutritional
      support in cancer. The nutritional needs of patients with cancer may differ from
      those of the healthy population due to hypermetabolism, impaired organ function,
      increased nutrient losses and therapy-related malnutrition. Patients with cancer
      often have increased requirements for both macro- and micronutrients due to long
      periods of undernutrition prior to diagnosis. The aim of nutritional support
      should be the prevention or reversal of malnutrition, and this should be
      initiated as early as possible to improve outcomes. Oral supplementation is a
      simple, non-invasive method of increasing the nutrient intake of those patients
      who are unable to meet nutritional requirements, despite dietary counselling.
      Enteral tube feeding is indicated for patients who are unable to meet their
      nutritional needs by oral intake alone, and has been shown to improve clinical
      outcomes. Novel approaches in oral supplementation include the use of
      eicosapentaenoic acid (EPA), a compound under investigation for its role in
      preventing and treating cancer-associated malnutrition. Individual studies
      suggest that EPA attenuates cancer-associated wasting and improves immune
      function. In addition, it has been shown to have anti-tumour effects and improve
      clinical outcomes. However, results are not consistent for all patient groups and
      further research is required.

PMID- 16437761
TI  - Aspects of taste and compliance in patients with cancer.
AB  - Taste alterations are common in patients with cancer, and can be the result of
      the disease itself and/or its treatment(s). Specifically, chemotherapy and/or
      radiotherapy to the head and neck area have been shown to induce significant
      taste changes. Alterations in taste are distressing for patients and can lead to
      food aversions, a reduction in food intake and nutritional deficits. Ultimately,
      this can lead to weight loss and, in severe cases, malnutrition, which has been
      associated with poor patient outcomes, including a negative effect on survival.
      Dietary counselling and advice tailored to the individual can improve nutritional
      status, and several effective strategies are available to accommodate taste
      changes and increase nutritional intake. Oral supplements may provide additional
      nutritional support when dietary intake is insufficient. The success of
      supplementation depends, however, on the product acceptability and on patient
      compliance over the long term. Patient compliance is linked to perceived
      supplement taste, which may be affected by a variety of taste changes reported by
      patients both before and after therapy, or as a consequence of disease
      progression. Supplements which offer a variety of flavours are likely to prove
      beneficial by helping to prevent taste fatigue. In addition, individuals appear
      to exhibit distinct preferences for particular flavours at different time points
      during treatment.

PMID- 16437762
TI  - Poor reports dog industry-academia liaison.

PMID- 16437763
TI  - Disturbing uptick in defibrillator recalls. Most pacemakers and implantable
      cardioverter/defibrillators work as they should, though the number recalled each
      year is growing.

PMID- 16437764
TI  - Some women need extra support after bypass surgery. Bras designed for women
      recovering from bypass surgery may ease pain and minimize infections.

PMID- 16437765
TI  - Heart of the holidays. 'Tis the season for many things--thanksgiving,
      celebration, fellowship, and good cheer. Oh yes, and heart attacks. We offer 12
      tips for a safer, healthier holiday season.

PMID- 16437766
TI  - Mainstream thinking on alternative therapies.

PMID- 16437767
TI  - Good news about cholesterol.

PMID- 16437768
TI  - Ask the doctor. A few months ago I gradually lost about 50% of the vision in my
      right eye. My ophthalmologist says this was caused by a small stroke. Am I now at
      higher risk for future strokes or heart attacks than someone who has not had a
      stroke?

PMID- 16437769
TI  - Benzodiazepines (and the alternatives).

PMID- 16437770
TI  - Anxiety sensitivity.

PMID- 16437771
TI  - Working off depression.

PMID- 16437772
TI  - Post-traumatic stress without trauma.

PMID- 16437773
TI  - What is the significance of the new warnings about suicide risk with Strattera?

PMID- 16437775
TI  - Triumph or tragedy? The moral meaning of genetic technology.

PMID- 16437776
TI  - Perinatal HIV transmission: a children's human rights perspective.

PMID- 16437777
TI  - Mandatory HIV testing and treating of child-bearing women: an unnatural, illegal,
      and unsound approach.

PMID- 16437778
TI  - Grave secrets: legal and ethical analysis of postmortem confidentiality.

PMID- 16437779
TI  - The ethics of managed care: a dose of realism.
AB  - This article examines the ethics of medical practice under managed care from a
      pragmatic perspective that gives physicians more useful guidance than existing
      ethical statements. The article begins by stating the authors' starting premises
      and framework for constructing a realistic set of ethical principles: namely,
      that bedside rationing in some form is permissible; that medical ethics derive
      from physicians' role as healers; that actual agreements usually trump
      hypothetical ones; that ethical statements are primarily aspirational, not
      regulatory; and that preserving patient trust is the primary objective. The
      authors then articulate the following concrete ethical guides: financial
      incentives should influence physicians to maximize the health of the group of
      patients under their care; physicians should not enter into incentive
      arrangements that they would be embarrassed to describe accurately to their
      patients or that are not in common use in the market; physicians should treat
      each patient impartially, without regard to source of payment, and in a manner
      consistent with the physician's own treatment style; if physicians depart from
      this ideal, they must tell their patients honestly; and it is desirable, although
      not mandatory, to differentiate medical treatment recommendations from insurance
      coverage decisions by clearly assigning authority over these different roles and
      by having physicians to advocate for recommended treatment that is not covered.

PMID- 16437780
TI  - Comments on the ethics of managed health care.

PMID- 16437781
TI  - Response to Professor Mark Hall.

PMID- 16437782
TI  - Markets and managed care ethics.

PMID- 16437783
TI  - Exploitation and commercial surrogacy.

PMID- 16437784
TI  - Prescription for death: a second opinion.

PMID- 16437785
TI  - Mother still knows best: cancer-related gene mutations, familial privacy, and a
      physician's duty to warn.

PMID- 16437786
TI  - X marks the spot while Casey strikes out: two controversial abortion decisions.

PMID- 16437788
TI  - Liposomal lidocaine improved intravenous cannulation success rates in children.

PMID- 16437787
TI  - Physician-assisted suicide and euthanasia: safeguarding against the "slippery
      slope"--The Netherlands versus the United States.

PMID- 16437790
TI  - Review: children permitted clear fluids </= 120 minutes before surgery have
      similar gastric volumes and pH values as those on standard fasts.

PMID- 16437789
TI  - Cooperative Care, Collaborative Research, Ubiquitous Information: The Human Being
      in the Center of Healthcare in the 21st Century. Opportunities through Medical
      Informatics, Biometry and Epidemiology. Proceedings from the gmds2004 meeting,
      September 26-30, 2004, Innsbruck, Austria.

PMID- 16437791
TI  - Topical chloramphenicol was not effective for acute infective conjunctivitis in
      children.

PMID- 16437792
TI  - Nurse home visits did not differ from standard care for prevention of recurrent
      child abuse.

PMID- 16437793
TI  - Multisystemic therapy improved adherence to blood glucose testing in adolescents
      with type 1 diabetes.

PMID- 16437794
TI  - A weight maintenance diet reduced bulimic symptoms in adolescent girls.

PMID- 16437795
TI  - After 3 months, low dose oral contraceptives reduced pain in adolescent girls
      with moderate to severe dysmenorrhoea.

PMID- 16437796
TI  - Biological mechanism for stress control. Proceedings of an international
      conference. Tokushima, Japan.

PMID- 16437797
TI  - Proceedings of the Symposium on Community-based Health Information Outreach,
      December 2-2, 2004, Bethesda, Maryland, USA.

PMID- 16437798
TI  - Trimethoprim reduced dysuria in women with symptoms of urinary tract infection
      but negative urine dipstick test results.

PMID- 16437799
TI  - Agriculture exposure and cancer. Proceedings of a symposium. November 19-22,
      2002. Oxford, United Kingdom.

PMID- 16437800
TI  - Review: wearing graduated compression stockings during air travel reduces the
      risk of deep venous thromboembolism.

PMID- 16437801
TI  - A home based, physical activity intervention increased physical activity,
      fitness, and vigour and reduced fatigue in sedentary women with early stage
      breast cancer.

PMID- 16437802
TI  - Glargine dose titration by patients and by physicians were equally effective for
      preventing severe hypoglycaemia.

PMID- 16437803
TI  - Web based care management improved glucose control in patients with poorly
      controlled diabetes.

PMID- 16437804
TI  - An educational booklet did not improve adherence or symptoms in patients
      prescribed thyroxine for primary hypothyroidism.

PMID- 16437805
TI  - Review: multidisciplinary interventions reduce hospital admission and all cause
      mortality in heart failure.

PMID- 16437806
TI  - The regulation of medical/scientific research practices involving experimentation
      on human beings.

PMID- 16437807
TI  - Review: multivitamins and mineral supplements do not reduce infections in elderly
      people.

PMID- 16437808
TI  - Multivitamin and multimineral supplements did not reduce reported infection days
      or related use of healthcare services in elderly people.

PMID- 16437810
TI  - Mothers' decisions about MMR vaccination were framed by their children's
      vulnerabilities and wider social trends.

PMID- 16437809
TI  - A simple risk score predicted 7 day stroke risk after transient ischaemic attack.

PMID- 16437811
TI  - Government as God: an update on federal intervention in the treatment of
      critically ill newborns.

PMID- 16437812
TI  - Genetic disability: a modest proposal to modify the ADA to protect against some
      forms of genetic discrimination.

PMID- 16437813
TI  - A survey of living will and advanced health care directives.

PMID- 16437814
TI  - The right to refuse medical treatment: where there is a right, there ought to be
      a remedy.

PMID- 16437815
TI  - A business ethics approach to contractual good faith and fair dealing: briefly
      modeled in selected managed healthcare contexts.

PMID- 16437816
TI  - Overcoming the legal obstacles to the creation of a futures market in bodily
      organs.

PMID- 16437817
TI  - Informed consent in Oklahoma: a search for reasonableness and predictability in
      the aftermath of Scott v. Bradford.

PMID- 16437818
TI  - The impact of foot position on electromyographical activity of the superficial
      quadriceps muscles during leg extension.
AB  - This study investigated variations in electromyographic (EMG) responses of the
      vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) due to foot
      position during leg extension. Twenty-four men and women (23.67 +/= 4.02 years)
      performed 8 repetitions at 70% of 8 repetition maximum with their leg medially
      rotated, laterally rotated, and neutral. Repeated-measures analyses of variance
      indicated that the highest normalized root mean square (NrmsEMG) for the VM and
      VL occurred with medial rotation, and the highest NrmsEMG for the RF occurred
      with lateral rotation. Significant NrmsEMG increases and median power frequency
      decreases occurred across repetitions regardless of foot position. Therefore,
      medial rotation produced the greatest muscle activation for the VL and VM,
      whereas lateral rotation produced the greatest activation in the RF. These
      findings are applicable to athletes or bodybuilders who are seeking to
      selectively increase either the size or performance of a specific muscle of the
      quadriceps group.

PMID- 16437819
TI  - Ending the genetic discrimination barrier: regaining confidence in preconception,
      prenatal, and neonatal genetic testing.

PMID- 16437820
TI  - Abortion and maternal-fetal conflict: broadening our concerns.

PMID- 16437821
TI  - Cultural feminism: it sounds good, but will it work? Application to a husband's
      interest in his wife's abortion decision.

PMID- 16437822
TI  - "Special weight" for best-interests minors in the new era of parental autonomy.

PMID- 16437823
TI  - UK and US adolescents perceived internet health information to be salient but of
      questionable credibility.

PMID- 16437824
TI  - The two faces of gag provisions: patients and physicians in a bind.

PMID- 16437825
TI  - Young women described the benefits of having advance supplies of emergency
      contraception but emphasised its use as a "last resort" rather than an
      alternative form of contraception.

PMID- 16437826
TI  - Marginalised HIV positive drug users felt that an HIV diagnosis created benefits
      as well as losses.

PMID- 16437827
TI  - Perceived barriers and benefits were factors in decision making about colorectal
      screening.

PMID- 16437828
TI  - UK palliative care professionals identified service infrastructure, patient and
      carer attitudes and characteristics, and practice culture as influencing place of
      death of patients with cancer.

PMID- 16437829
TI  - Genetic screening and insurance: too valuable an underwriting tool to be banned
      from the system.

PMID- 16437830
TI  - Galen and the best of all possible worlds.

PMID- 16437831
TI  - The uses of laughter in Greek culture.

PMID- 16437832
TI  - John of Alexandria again: Greek medical philosophy in Latin translation.

PMID- 16437833
TI  - Notes on the text of John of Alexandria.

PMID- 16437834
TI  - Spiritual pregnancy in Plato's "Symposium".

PMID- 16437835
TI  - Subject to emotion: exploring madness in "Orestes".

PMID- 16437836
TI  - Galen's "De constitutione artis medicinae" in the Renaissance.

PMID- 16437837
TI  - The harmonious pulse.

PMID- 16437838
TI  - Two notes on Greek suicide.

PMID- 16437839
TI  - A textual note on Galen, on the powers of foodstuffs I 1.3 (P. 202.17 Helmreich).

PMID- 16437840
TI  - Two problems in ancient medical commentaries.

PMID- 16437841
TI  - A Note on Hippocrates, De Morbis II 1, 4 a.

PMID- 16437842
TI  - The Death of Chiron: Ovid, Fasti 5.379-414.

PMID- 16437843
TI  - Greek love at Rome.

PMID- 16437844
TI  - Rouge and crocodile dung: notes on Ovid, Ars 3.199-200 and 269-70.

PMID- 16437845
TI  - Structures of care in "The Iliad".

PMID- 16437846
TI  - Punishment and the physiology of the "Timaeus".

PMID- 16437847
TI  - Statius and insomnia: allusion and meaning in "Silvae" 5.4.

PMID- 16437848
TI  - Levels of explanation in Galen.

PMID- 16437849
TI  - Fragments of lost Hippocratic writings in Galen's glossary.

PMID- 16437850
TI  - The Hippocratic treatise "On Anatomy".

PMID- 16437851
TI  - Doubts about other minds and the science of physiognomics.

PMID- 16437852
TI  - Emperors, aristocrats, and the Grim Reaper: towards a demographic profile of the
      Roman elite.

PMID- 16437853
TI  - The wounds in "Iliad" 13-16.

PMID- 16437854
TI  - The death of Cyrus the Younger.

PMID- 16437855
TI  - "On Sterility" ('HA X'), a medical work by Aristotle?

PMID- 16437857
TI  - The Greek anthropocentric view of man.

PMID- 16437858
TI  - The funerary inscription of the physician of Caecilia Crassi in the Fogg Art
      Museum.

PMID- 16437856
TI  - Greek embryological calendars and a fragment from the lost work of Damastes, "On
      the care of pregnant women and of infants".

PMID- 16437859
TI  - Roman life expectancy: Ulpian's evidence.

PMID- 16437860
TI  - Medicine, music, and magic: the healing grace of Pindar's "Fourth Nemean".

PMID- 16437861
TI  - The bed-wetters in Lucretius 4.1026.

PMID- 16437862
TI  - Therapeutic touch in Sophokles' "Philoktetes".

PMID- 16437863
TI  - Genital phobia and depilation.

PMID- 16437864
TI  - The skull from tomb II at Vergina: King Philip II of Macedon.

PMID- 16437865
TI  - The wounding of Philip II of Macedon: fact and fabrication.

PMID- 16437866
TI  - Anthropology and spirit possession: a reconsideration of the Pythia's role at
      Delphi.

PMID- 16437867
TI  - Are the preoperative histological findings accurate for the choice of the
      surgical approach in ulcerative colitis associated with colorectal
      cancer/dysplasia?

PMID- 16437868
TI  - [Locally advanced and recurrent pelvic colorectal carcinoma: results of
      aggressive surgical treatment].
AB  - Pelvic exenteration has been described as a formidable procedure in cases of
      advanced or recurrent pelvic cancers for a variety of primary tumors, including
      colorectal, gynaecologic and urologic. We report our 14-year experience in a
      community hospital with 37 cases who underwent pelvic exenteration for recurrent
      (n = 15) or locally advanced (n = 22) colorectal cancers. At a median follow-up
      of 36 months, the median survival was 24 and 36 months, respectively, and the 5
      year actuarial survival was 18% and 44%.

PMID- 16437869
TI  - [Rectal cancer: locoregional recurrence in relation to surgical and complementary
      treatment].
AB  - Much recent data have been published on the risk of local recurrence (LR)
      following curative surgery for rectal cancer and the impact of adjuvant therapy.
      On the other hand, improvements in surgical techniques, as the total mesorectal
      excision, have apparently reduced the risk of LR. Furthermore, in selected cases,
      neoadjuvant therapy seems to reduce much more the incidence of LR. A list of
      prognostic factors which affect the onset of LR, other than the different
      procedures, was considered. To investigate such evidences a retrospective
      analysis was undertaken in our series, focusing on examination of the employed
      techniques as potential predictors of local recurrence. Thus, in a 18-yr-period
      (1986-2003), two hundred and ninety-five patients who had undergone elective
      curative surgical resection of rectal cancer were included in the study. The
      demographic, operative and follow-up data were collected retrospectively. All
      patients underwent total mesorectal excision, whereas neoadjuvant therapy was
      performed in a selected series of patients, according to defined entry criteria
      patterns. Results evidenced LR in 7.1% of patients and occurred between 6 months
      to 8 year following surgery. Comparisons were made between patients who had
      different surgical procedures; indeed sphyncter saving procedures correlated with
      a higher incidence of LR rather than abdomino-perineal resection. Pelvic
      recurrences were observed more frequently compared to the anastomotic ones. A
      limited number of patients with LR underwent surgery due to the associated
      condition of metastatic lesions; the follow-up related to such series evidenced a
      mortality rate of 57% within 3 year from reoperation. A low local recurrence rate
      can be achieved after total mesorectal excision (TME) without preoperative
      radiotherapy. Our results suggest that preoperative radiotherapy may be employed
      only for those patients who are at a higher risk for local recurrence.

PMID- 16437870
TI  - Combined multistep approach in a locally advanced rectal cancer with sacral
      invasion: case report.
AB  - Composite pelvic resection with sacrectomy may provide good local control in case
      of locally advanced rectal cancer infiltrating the sacral bone. A combined
      multidisciplinary approach including chemotherapy and radiotherapy is here
      presented for a case of rectal tumor invading the sacrum.

PMID- 16437871
TI  - Multidisciplinary approach to locally advanced rectal cancer: results of a single
      institution trial.
AB  - Locally advanced rectal cancer carries out a dismail prognosis despite optimal
      surgery in terms of local and distant relapses. Neoadjuvant chemoradiation offers
      good results with tumor downstaging and downsizing and leads to more radical
      surgery with conservative intent. Selection of patients and an intensive
      chemotherapy may improve long term results. Our experience with a combined
      polichemotherapy and radiotherapy for low advanced rectal cancer is presented.

PMID- 16437872
TI  - [Prognostic factors and results of surgical treatment of pelvic recurrence of
      rectal cancer].
AB  - From 1990 to 2003 have been admitted 105 patients with pelvic recurrence from
      rectal cancer. Fifty-nine patients have been selected and 25 patients underwent
      surgery. We evaluate the prognostic factors and the 3 years disease-free
      survival. The 60% of the patients after R0 resection and the 20% of the patients
      who underwent R1-R2 resection are alive. The evaluation of the prognostic factors
      allows early diagnosis of recurrence with a better long time survival.

PMID- 16437873
TI  - [Treatment of local recurrences of rectal cancer].
AB  - In this work we report the results of 27 patients who underwent a second surgical
      operation for local disease recurrence after colorectal surgery for cancer. We
      describe the different intervention we performed and for everyone of them we
      analyze intraoperative mortality and morbidity, long term survival and quality of
      life related.

PMID- 16437874
TI  - [Contribution of intraoperative radiotherapy in the control of local recurrences
      of rectal cancer].
AB  - Local recurrence (LR) is a major problem following curative resection of rectal
      cancer. Intraoperative radiation therapy (IORT) is considered an ideal boost
      technique for increasing the dose of radiation therapy within a restricted area
      without introducing a significant toxicity. The aim of this study is to present
      the results of a multimodality treatment containing external beam irradiation,
      chemotherapy, surgical resection, and IORT delivered by a movable linear
      accelerator (NOVAC7, Hitesys SpA, Italia), employed in a "traditional" operating
      room.

PMID- 16437875
TI  - [Neoadjuvant radiochemotherapy of rectal cancer: our experience].
AB  - Postoperative chemoradiotherapy is the recommended standard therapy for patients
      with locally advanced rectal cancer. In recent years, encouraging results with
      preoperative radiotherapy have been reported. From 2000 at January 2005 we
      treated 11 patient and our results suggest that preoperative radiotherapy
      combined with chemotherapy increases the chances of tumor downstaging and
      downsizing and facilitates sphincter-sparing surgical procedures.

PMID- 16437876
TI  - [Multimodal approach to rectal carcinoma with hepatic metastasis].
AB  - BACKGROUND: The role of surgery in the treatment of rectal cancer has been
      demonstrated worldwide. Moreover, curative liver resection of colorectal liver
      metastases is the only treatment offering a chance of long-term survival.
      Unfortunately, the liver resection can be performed in only 10% of the patients.
      AIM: In order to extend the frontiers of surgical indications in the treatment of
      liver metastases from colorectal cancer, we describe, in the video, a multimodal
      approach to rectal cancer with liver metastasis in the right lobe. Patient and
      methods. A 51 years old woman was admitted to our Department for adenocarcinoma
      of the distal rectum and a resectable solitary synchronous liver metastasis
      located across the right and the middle hepatic vein. Unfortunately, the future
      remnant liver was too small, risking severe post-operative liver failure. For
      this reason, a portal vein embolization or occlusion has been proposed. First of
      all, the patient has been submitted to laparoscopic low anterior resection with
      simultaneous right portal vein ligature. Two months later, after a CT estimation
      of liver volume in vivo, she was submitted to right hepatectomy (open surgery).
      RESULTS: Both postoperative courses were uneventful. CONCLUSIONS: As a
      preparation for large hepatic resection for liver rectal metastasis the
      laparoscopic ligature of the right portal vein performed simultaneously to the
      laparoscopic low anterior resection is feasible and safe.

PMID- 16437877
TI  - [Correlation between positive lymph nodes and metastasis of colorectal cancer.
      Personal experience].
AB  - The authors, in a group of 190 patients treated with curative surgery for
      colorectal cancer, have studied the correlation between lymph nodes positive of
      primary tumor and rising of liver metastases. Even if the B2 stage nodes were
      negative, liver metastases were found in 6.25% of the patients probably due to an
      understaging; in C1 + C2 stage the rate of liver metastases was 28.1%, however in
      this group has not been demonstrated a statistical correlation with the number of
      positive nodes as a predictive negative prognostic factor.

PMID- 16437878
TI  - [En bloc lymphadenectomy for colorectal cancer, number of lymph nodes and ratio
      as prognostic factors: personal experience].
AB  - The authors have re-evaluated the lymph node status of 221 patients operated on
      for colorectal cancer and submitted to a five years follow-up in order to
      evaluate the role of the number of positive nodes and its "ratio" as negative
      prognostic factors of recurrences. In the patient classified as B2 stage, the
      recurrences occurred in spite of adequate number of negative nodes, in C1 + C2
      stage the lymph node "ratio" could be considered an appropriate prognostic
      factor.

PMID- 16437879
TI  - [Pelvic recurrence in the era of integrated treatments of rectal cancer].

PMID- 16437880
TI  - [Pelvic recurrence of rectal cancer: our experience].
AB  - Isolated recurrence of rectal carcinoma have been reported from 7% to 33% with a
      median of 15. Increasing recurrence is associated with increasing Dukes's stage.
      Patient who have recurrence after a low-anterior resection are more likely to
      present with non fixed, surgically correctable lesion versus recurrences after
      abdominoperineal resection. The most common symptom related to pelvic recurrence
      is pain, which may be perineal or radiate to the lower extremities. The diagnosis
      of a locally recurrent rectal cancer was obtained with CT; imaging is the first
      step to estimate the extent and location of the local tumor growth and the
      presence or absence of distant metastases. The most common location is at or
      around the anastomosis and the presacral region. Apart from distant metastases
      locoregional recurrence is the most important factor determining prognosis and
      survival. If an R0 resection can be performed, a 5-year survival rate of 20-30%
      can be achieved. Local or locoregional recurrence implies the reappearance of
      carcinoma after an intended complete removal of the tumor. For rectal cancer, the
      adjacent organs include the perineum, bladder and vagina, and LR failure includes
      perineal or pelvic lesions. Total pelvic exenteration is performed in patients
      with local recurrence of rectal cancer and a 5-year suvival rate of 30-40% was
      achieved. For patient with unresectable recurrence, chemotherapy and radiation
      contribute to a better quality of life and prolong survival. While radiotherapy
      may reduce recurrence, it is now apparent that total mesorectal excision is the
      most effective modality, with rates as low as 5%. The anastomotic recurrence that
      can be locally resected, the best approach for long-term survival is an extensive
      surgical procedure requiring en bloc removal of adjacent organs and pelvic
      structures so called composite resection. Intraoperative radiotherapy and
      brachytherapy, and/or preoperative chemoradiation may provide better results in
      future. While radioterapy remains the most common antineoplastic modality used
      for palliation of symptoms, surgical resection remains the mainstay of curative
      treatment for carcinoma of colon and rectum.

PMID- 16437881
TI  - [Neoadjuvant radiochemotherapy of rectal carcinoma: retrospective analysis of a
      personal experience].
AB  - Even if surgical resection continues to be the mainstay of treatment in rectal
      cancer, preoperative chemoradiation may downstage locally advanced rectal cancer,
      in some cases with no residual tumors. Compared with surgery alone, preoperative
      radiotherapy and chemotherapy improves outcomes in patients with locally advanced
      rectal cancer. In the present review we summarize the results of preoperative
      chemoradiation therapy in a group of 15 patients who underwent surgical resection
      with total mesorectal excision (TME) for advanced mid and low rectal cancer from
      February 2002 to February 2004.

PMID- 16437882
TI  - [Lymphoscintigraphic localization of sentinel lymph nodes in colorectal carcinoma
      in early stage: results of a single center study and proposal of a multicenter
      protocol].
AB  - In colorectal cancer the sentinel node dissection may help to identify any
      unusual mesenteric lymphatic drainage pattern from the primary tumor site
      (ex/skip metastases); assuming that accurate pathological staging is critical for
      therapeutic decisions we are conducing a study to evaluate the feasibility of the
      sentinel node technique in colorectal neoplasms and its overall accuracy in
      predicting regional lymph nodes metastases for appropriate staging. From February
      2001 to September 2004 we included in this study 30 patients with rectal lesions
      or degenerate colonic polyps not radically excised by endoscopy. Lymphatic
      mapping was performed with low molecular weight albumin colloid labelled with
      500Mci of 99mTc in a 2 ml volume and injected submucosally by an endoscopic route
      at the four cardinal points around the tumor, the afternoon before the surgical
      procedure, both in case of colonic or rectal lesions. Scintigraphic images were
      obtained with a gamma camera fitted with a general purpose collimator. The day of
      the intervention, a hand held gamma detecting probe (Scintiprobe m100, Pol-Hi
      Tech, Italy) was employed to detect the "hot" nodes, in vivo and ex vivo. These
      lymph nodes were tagged with a stitch in vivo; the specimen was removed by a
      standard resection and SLN were dissected ex vivo and sent separately for
      pathological examination. In case of rectal lesions, the sentinel nodes were
      searched ex vivo into mesorectal fat in case. All lymph nodes, including blue or
      hot ones, were embedded separately for preparation of paraffin sections and
      haematoxylin and eosin staining. Sentinel lymph node were submitted to multi
      seriate sections in order to look for micrometastases. Using the radioactive
      tracer, sentinel lymph nodes were successfully identified in 27 out of 30
      patients. Concordance between SLNs and nodal status was observed in 23 out of 27
      cases (85%); two patients (7.4%) were upstaged, as SLN was the only site of
      metastases. In another two cases we observed no concordance between negative
      sentinel node and non sentinel nodes (false negative rate, 7.4%). Starting from
      this experience we are proposing a multicentric trial concerning the value of
      sentinel node technique in rectal cancer and in early colorectal cancers detected
      by screening programs.

PMID- 16437883
TI  - [Feasibility and reliability of the study of sentinel lymph nodes with
      immunohistochemical technique in colonic carcinoma].
AB  - Sentinel lymph node sampling, in patients with resectable colon cancer, improved
      identification of lymph node disease and identified patients likely to benefit
      from adjuvant therapy. This study examined whether sentinel node sampling
      accurately predicted lymph node status for patients with resectable colon cancer.

PMID- 16437884
TI  - [Verrucous carcinoma of the anus or Buschke-Lowenstein tumor of the anus: staging
      and treatment. Report of 3 cases].
AB  - INTRODUCTION: Giant condyloma acuminatum or Buschke Lowenstein tumor of the
      anorectal and perianal regions is an uncommon entity that commonly affects
      genitalia. These are slow-growing, expansive, cauliflower-like, destructive
      lesions that could propagate to vulvar and vaginal region, rectum and bladder.
      The hallmark of the disease is the high rate of recurrence (66%) and malignant
      transformation (56%). No distant metastases usually occur. The median number of
      recurrences are 2 (range, 1-7). MATERIALS AND METHODS: At the Oncological
      Surgical Department, University of Turin, three patients were diagnosed with a
      Buschke Lowenstein tumor. In two cases immunodeficiency was evidentiated (HIV in
      one case and ciclosporin treatment in the second one). The lesions were up to 15
      cm of diameter and in one case scrotum was invaded. In another case a lesion in
      sacral region was observed. All patients were studied with anoproctoscopy, CT
      scan, pelvic magnetic resonance and lymphoscintigraphy for following biopsy of
      inguinal sentinel node for potential malignancy. All patients were submitted to
      extensive local surgical treatment. RESULTS: No mortality was observed. In one
      case we observed a late anal stenosis treated with local dilatations. No more
      complications were observed. One patient with a small persistence of the disease
      was treated with cryotherapy. All inguinal nodes revealed negative to definitive
      histological exam, that confirmed the diagnosis of Buschke Lowenstein tumor of
      the primary lesion. CONCLUSIONS: Buschke Lowenstein tumors are rare but extensive
      lesions difficult to treat. Local surgery with elettrocautery or laser is the
      first treatment of choice, even if abdominoperineal amputation sec. Miles could
      be considered in case of extremely extensive lesions or multiple and extensive
      recurrences. Others treatments proposed are radiotherapy, chemotherapy,
      interferon, iniquimod and so on. Other studies are requested to value the best
      treatment.

PMID- 16437885
TI  - Anal carcinoma occurring in Crohn's disease patients with chronic anal fistula.
AB  - This paper reports six patients with perianal Crohn's disease (CD), who developed
      anal cancer in chronic anal fistulas. Tumors have been often diagnosed at an
      advanced stage and had a worse prognosis than cancers arising in the general
      population as tumor symptoms may mimic symptoms of CD, resulting in delay in
      diagnosis. Patients with perianal CD should undergo a careful surveillance
      program for ano-rectal carcinoma, including routine biopsy of any suspected
      lesion. When malignancy is found, an aggressive surgical approach and
      complementary therapy are mandatory.

PMID- 16437886
TI  - [The technique of sentinel lymph nodes in patients with anus neoplasm].
AB  - Anal cancer is a rare neoplasm, representing 1-2% of all large bowel cancers.
      Surgical excision by abdominoperineal resection has been the standard treatment.
      In the 1920s and 1930s inguinal node dissection was included in the surgical
      management of these patients. In the 1950s it was evident that the morbidity
      associated with lymphnode dissection was much greater than any survival benefit
      and this procedure was abandoned. Since 1974 "multimodality treatment" with a
      combination of radiation and chemotherapy has become the standard treatment.
      Synchronous inguinal lymph node metastases occur in 10-25% of patients and
      metachronous metastases have been reported in 5-25% of cases. Inguinal lymph node
      metastases are an independent prognostic factor for local failure and overall
      mortality by a multivariate analysis of EORTC. In order to assess inguinal lymph
      node status we applied the sentinel node technique to patients affected by anal
      cancer. Fifteen patients were studied with a lymphoscintigraphy after peritumoral
      injection of 37 MBq of Tc-99m colloid. A surgical biopsy of sentinel node was
      performed in all patients with a detection rate of 100%. Inguinal metastases
      occurred in 4 patients (26.6%), and in 2 cases metastases were located
      bilaterally. Twelve patients (80%) were treated in local anesthesia and they were
      dismissed the same day of surgical procedure. No major complication occurred.
      Considering the strong correlation between prognosis and node involvement, we
      consider this technique an important and simple method for evaluating the lymph
      node status and for an adequate pre-treatment staging of anal carcinoma.
      fundamental in the choice of radiation plane. In particular inguinal radiotherapy
      could be reserved for N1 patients only. avoiding the morbidity related to this
      procedure in N0 patients. Further studies are required to confirm these results
      and a consistent follow-up will be necessary to evaluate long-term results
      particularly in those patients (N0) who have not been treated with prophylactic
      inguinal radiotherapy.

PMID- 16437887
TI  - [Thermal ablation by radiofrequency of hepatic metastasis of colorectal cancer:
      short-term results].
AB  - Radiofrequency (RF) was used to ablate 42 colorectal liver metastases in 20
      patients (10 males and 10 females) in a four years period. Median age was 62.2
      years, 36 lesions (75%) had 3 cm diameter or less. An open surgical approach was
      adopted in 13 patients, whereas a percutaneous one in 14. On 27 surgical
      sessions, RFA was used in 49 procedures for a total of 81 needle applications.
      Morbidity was 6.0% (3 cases), one patient died on third po day for myocardial
      infarction. No differences in terms of complete ablation rate was observed in the
      two approach's groups. Overall survival was 65% with a median follow-up of 18.5
      months.

PMID- 16437888
TI  - [Parenchyma sparing: evolution of the resective surgical approach of hepatic
      metastasis from the colorectum].
AB  - Liver surgery for colorectal metastasis has moved toward a parenchymal sparing
      strategy in order to reduce postoperative liver failure, to resect an higher
      number of metastases and to allow a future re-resection. Patients undergone
      hepatectomy in our Department before and after 1999 were retrospectively
      compared. In the recent years surgery became more aggressive: a higher number of
      patients with multiple and bilateral lesions were treated. Short-term results
      improved in the recent series. After 1999, the rate of wedge resections was
      significantly increased with the same oncological radicality and with improved
      long-term results. Moreover, parenchymal sparing strategy allowed a higher re
      resection rate in patients with liver recurrence.

PMID- 16437889
TI  - [Major and repeated liver surgery in the multimodal treatment of synchronous and
      metachronous metastasis of colorectal cancer].
AB  - At the present, surgical treatment still represents the only chance of cure for
      liver metastases from colorectal cancer. Moreover in the last years the new
      chemotherapic adjuvant and neoadjuvant regimens and the use of radioablative
      techniques as radiofrequency have improved resectability and even survival.
      Besides, iterative surgery seems to show more and more encouraging results in
      terms of disease-free and overall survival, sometimes even in patients already
      resected for extrahepatic disease. The golden rule is in fact to try to perform
      every time an R0 resection, with no macro- and possibly microresidual disease.

PMID- 16437890
TI  - [Colorectal liver metastases resected with safe margin achieved by tissuelink
      monopolar floating ball].
AB  - BACKGROUND: Nowadays many technological devices are present in hepatic surgery to
      permit safer liver resections. Main purpose is decrease the intraoperative blood
      loss. The aim of this study is to analyze our initial experience in hepatic
      resections for liver metastasis using the new water-cooled, high-density,
      monopolar device, the Tissuelink Monopolar Floating Ball and Dissecting Sealer
      (Tissuelink Medical, Inc., Dover, NH). MATERIALS AND METHODS: We analyzed
      patients who underwent hepatic surgery for metastases from colorectal cancer
      between January 2003 and December 2004. Sex, age, type of surgical procedure,
      duration of the surgical procedure, blood loss, use of vascular clamping of the
      liver, length of hospital stay, morbidity, and mortality were analyzed. RESULTS:
      Three liver resection, one segmentectomy and two limited resections were
      performed with the use of these new devices. In one case the devices was used to
      increase safe free margin of hepatic resection. Average blood loss was 150 ml
      (range, 50 to 300 ml). No mortality or morbidity were recorder. CONCLUSIONS: In
      conclusion, this new device permits a bloodless liver resection avoiding vascular
      clamping. In plus the effect of radiofrequency waves can be useful to enlarge
      free resection border in patients submitted to hepatic resection without
      macroscopically safe margins. Prospective randomized studies are needed in order
      to establish the effective usefulness.

PMID- 16437891
TI  - [Isolated resection of the caudate lobe in metastasis of colorectal cancer].
AB  - The presence of metastatic lesions confined to the caudate lobe (CL or segment I)
      is quite a rare event. Even more rare is the decision to perform an isolate CL
      resection. Segmental resection in the liver is justified by the evidence that
      primary and secondary lesions, in early stage, are confined to the originating
      segment, and therefore a segmentectomy can be considered for the CL as well.
      Anatomy of the CL was deeply studied through the years since the surgical
      approach to this liver segment requires a detailed knowledge of its surgical
      anatomy and only after 1985 the surgical technique for CL isolate resection was
      established. We report our experience with 1 case of isolate colo-rectal
      metastasis confined to the caudate lobe and describe the surgical technique
      employed.

PMID- 16437892
TI  - [Hepatic resection of metastasis of colorectal carcinoma: analysis of long-term
      prognostic factors of outcome].

PMID- 16437893
TI  - [Experience of a peripheral center in the surgical treatment of hepatic
      metastasis from colorectal cancer].
AB  - Surgical resection is still the first therapeutic option in patients with
      resectable colorectal cancer metastatic to the liver. Application of
      radiofrequency energy has been used in patients who did not meet the criteria for
      resectability and yet were candidates for a liver-directed procedure based upon
      the presence of liver-only disease. Hepatic resection has evolved in the last two
      or three decades from a procedure with associated mortality rate of up to 20% in
      the early 80s to usually less than 5% in patients undergoing liver resection
      thereafter. This improvement in morbidity and mortality is multifactorial;
      despite the increased safety of liver operations, hepatic resection still remains
      a complex surgical procedure with serious potential morbidity. The experience
      with liver resections and/or radiofrequency ablations, for colorectal cancer
      metastatic to the liver, performed at a medium-volume center (15 cases in 4
      years) is presented. Some features of the metastatic disease, including the
      number, size and location of metastases are identified. The perioperative
      mortality is 0, morbidity for non surgical complications is 40%. In this series
      the reported overall 1-yr survival is 80%, 2-yr is 67%. This paper reviews the
      experienced factors that have defined the morbidity and mortality associated with
      liver surgery.

PMID- 16437894
TI  - [Cryosurgery with transpleurodiaphragmatic approach in the treatment of non
      resectable and recurrent hepatic metastasis from the colorectum].
AB  - Cryotherapy allows the destruction of unresectable liver malignancies. The
      abdominal approach is uneasy for recurrent colorectal metastases located in the
      upper part of the liver and close to the inferior vena cava, the hepatic veins
      and the diaphragm. A transpleurodiaphragmatic access was employed. From 1999 to
      2003, ten patients with recurrent colorectal liver metastases underwent
      transdiaphragmatic cryotherapy via a right thoracotomy. Median diameter was 30
      mm. One to 4 cryoprobes were used, depending on the size and location of the
      metastasis. There were no operative deaths, and only 3 patients developed minor
      complications. Computerized tomography examination of the liver performed one
      week, three months after cryotherapy, assessed treatment completeness in all
      patients. At 14 months, 9 patients were alive and 6 were disease-free. Two
      patients had liver recurrences outside the cryolesion. A transthoracic access may
      represent the safest and easiest surgical approach for liver tumor cryoablation
      in selected patients with non resectable recurrent metastases of the upper liver.

PMID- 16437895
TI  - Intra-arterial chemotherapy for liver metastases from colorectal cancer.
AB  - The aim was to investigate whether intra-arterial infusion of chemotherapy
      improves response to treatment in unresectable liver metastases from colorectal
      cancer. We treated 14 patients (pts) with intra-arterial chemotherapy. Arterial
      catheters were placed via percutaneous access. Treatment schedule was: 5-FU and
      mitomycin-C on day 1 every 21 days. Six pts also received from day 3 for 5 days,
      a continuous intra-arterial 24-hr infusion of interleukin-2 (IL-2). We had only
      one case of toxicity drug-related > grade 2 (neutropenia). We observed 2 partial
      response (PR) and 5 stable disease (SD). Median time to disease progression (TTP)
      and median survival (OS) were, respectively 4 and 15 months.

PMID- 16437896
TI  - [Intrahepatic cholangiocarcinoma: case report].
AB  - The primitive tumors of the liver are relatively rare in the Western countries
      (around the 0.7% of all the neoplasms) while they present more elevated incidence
      in Africa and in the South Asian East. While the hepatocellular carcinoma rises
      up in the 50-70% of the cases in livers cirrosis, this correlation is not valid
      for the form of carcinoma to departure from the learned intra and extra biliar.
      The etiology of the intrahepatic colangiocarcinoma (CC) stays unknown. They have
      stayed observe, on the other hand, of the conditions sometimes correlated to the
      development of the CC (Caroli morbs, ulcerative colitis, asbestosis). The CC
      usually rises up from the epithelial cells of surface that delimit the biliary
      ducts, although different studies suggest that these tumors can also originate
      from the learned smaller biliary ducts, from the hepatic cysts of the policistic
      illness and from the complexes of von Meyenburg. The low incidence of the CC, the
      clinical atypical debut, the not facility of a precise diagnosis have aroused our
      interest so that the present job wants to be a modest scientific contribution to
      this type of pathology.

PMID- 16437897
TI  - [Intrahepatic biliary cystadenoma: case report].
AB  - According to the OMS classification of the epithelial benign neoplasm of the
      liver, the adenomas represent the most important group. In literature an increase
      of their incidence in the last years is reported especially in the female sex, in
      relationship to the diffusion of the use of hormonal contraceptives. The biliar
      cistoadenoma (BCA) represents a not frequent neoplasm of the liver that has
      origin on the inside of the liver, and less frequently from the extrahepatic
      biliar system. The surgical interest is underlined by the potentiality of the
      malignant evolution of the lesion and by its high tendency to the relapse. The
      real difficulty is represented by differential diagnosis from the other cystic
      lesions of the liver and by the need of its radical excision and therefore of
      real hepatectomy.

PMID- 16437898
TI  - [Surgical treatment of hepatocellular carcinoma: prognostic factors for long-term
      disease-free survival and tumor recurrence].
AB  - Hepatocellular carcinoma mainly develops in a cirrhotic liver; in the majority of
      the patients chronic hepatitis or cirrhosis are virus-related and/or
      postalcoholic. Liver resection is the gold standard treatment when there is no
      multifocality of the tumor and liver disease is not advanced (patients with Child
      Pugh A score, or B in selected cases). In our experience the presence of vascular
      invasion and satellite nodules is clearly related to a decreased rate of disease
      free survival and a higher percentage of intrahepatic recurrence.

PMID- 16437899
TI  - [Interstitial laser treatment of small hepatocarcinoma on cirrhosis without
      anesthesia: feasibility study].
AB  - OBJECTIVE: We evaluated if interstitial laser photocoagulation (ILP) under
      ultrasound (US) guidance of intraparenchymal small HCC (<2 cm) in cirrhosis can
      be safely and effectively performed without any anesthesia. PATIENTS AND METHODS:
      Twelve cirrhotic patients with 14 nodules of HCC (diameter 1.2-2.0 cm; mean: 1.7)
      underwent ILP. All procedures were performed without local or general anesthesia.
      Necrosis of the nodules was evaluated with triphasic contrast-enhanced CT.
      RESULTS: Post-treatment CT showed complete necrosis in all cases. Pain occurred
      in 5 patients during the treatment was treated with iv pain-killer and only in 1
      case the procedure was stopped before the scheduled time. No major complication
      occurred. CONCLUSIONS: ILP under US guidance is feasible without any anesthesia
      in patients with small intraparenchymal HCC.

PMID- 16437900
TI  - [Etiopathogenic hypothesis on carcinoma of the gallbladder: our study].
AB  - The authors are interested in determining causes of gallbladder cancer (GBC). By
      this intention, they theorize a correlation between genetic modifications (which
      are responsible of malignant transformation of biliary epithelium) and some
      intestinal infections. From 1999 to 2004 they observed 15 GBC and all 15
      gallbladder have been analyzed histologically and from microbiological aspect; by
      these means from 1999 till 2004 they have studied also 30 persons with
      colelithiasis. The authors noticed that bile of both groups contained, in three
      cases in the first and in 8 cases in the second, a germ named Escherichia Coli
      which normally lives in intestine, while in 10 operated gallbladders of the first
      group and 12 of the second there was a positive for k-ras. They are studying to
      confirm their theories.

PMID- 16437902
TI  - [Prognostic factors of pancreatic carcinoma: analysis of the 5-year-survivor
      cases].
AB  - Pancreatic carcinoma remains a letal disease with an overall 5-year survival of
      less than 5%. Recent reports of increases in actuarial survival after resection
      have determined some optimism. Our objective was to identify the actual 5-year
      survival rate of patients with pancreatic carcinoma who underwent a resection
      with curative intent, analyzing those factors associated with a more favorable
      prognosis.

PMID- 16437901
TI  - [Pancreatic tumor: unusual onset of Von-Hippel Lindau syndrome].
AB  - The Von-Hippel Lindau (VHL) disease is a rare genetically determined syndrome.
      Clinical course depends on the occurrence of multiple tumors as central nervous
      system tumors, phaeochromocytoma and renal cell carcinoma. We describe the second
      case in the literature reporting about a patient affected by a pancreatic
      neuroendocrine tumor as the first clinical sign of VHL disease. It has been
      showed that only a strict follow-up can effectively improve survival. Based on
      the present case, the follow-up of patients affected by VHL syndrome should
      routinely include functional tests and imaging exams of the pancreas.

PMID- 16437903
TI  - [Duodenocephalopancreatectomy for periampullary neoplasm in elderly patients].
AB  - As life expectancy continue to increase, many elderly patients may be considered
      for pancreaticoduodenal resection. The purpose of the study was to review our
      experience with pancreatic resection for periampullary evaluating immediate and
      long-term results in patients aged 75 or older.

PMID- 16437904
TI  - [Enucleation-resection of pancreatic neuroendocrine tumors: 25 years of
      experience].
AB  - From 1980 to 2004, out of 109 patients who underwent surgery for neuroendocrine
      pancreatic tumor, 33 had a simple tumor excision. Seventy-two percent of cases
      were insulinomas. Age, sex, site and size of the tumor, associated diseases,
      hospital stay and complications were retrospectively reviewed by the clinical
      records. Patients (12 males and 21 females) averaged 56.8 years, range 20-86.
      Mean size of the tumor was 1.7 cm and 54.5% were in the pancreatic head; 78.8% of
      cases had medical associated diseases. Hospital stay was 12 days (median; range,
      6-81 days) and mean period of gastric suction was 4 days. Forty-eight percent had
      a uneventful postoperative course. Complications were divided in early (related
      to pancreatic surgery, related to general open surgery and medical) and late
      events. Complication related to pancreatic surgery were 6/33 (18%); 5 pancreatic
      fistulas (4 low output) and 1 acute pancreatitis, while 5/33 had a general
      surgery complication (2 leacking due to gastric and duodenal associated
      operations). Medical complications were recorded in 13 cases. Late complications
      occurred in 4 cases (2 incisional hernias, 1 pseudocyst and 1 keloid). No patient
      was re-operated for pancreatic complications; 1 was reoperated for evisceration
      and 1 for hyper-parathyroidism in the early post-operative period. No mortality
      occurred. Re-evaluation of the clinical records in order to be submitted to
      laparoscopic surgery excluded 17/33 cases (51%) as candidate to laparoscopic
      approach.

PMID- 16437905
TI  - [Signet-ring cell carcinoma of the Vater's ampulla: report of a clinical case].
AB  - We report the case of a sixty-six year-old man admitted at our hospital with a
      suspected malignant tumor of the ampulla of Vater. The patient underwent a
      Pylorus-preserving pancreatico-duodenectomy. Histology showed a signet-ring cell
      carcinoma of the ampulla of Vater. This case is the 13th report in the literature
      of a signet-ring cell carcinoma of the ampulla of Vater.

PMID- 16437906
TI  - [Cerebellar metastasis from pancreatic adenocarcinoma: report of a clinical
      case].
AB  - We describe a case of a metacronous cerebellar metastasis from pancreatic
      adenocarcinoma occurred in a 67 years old male. Central nervous system metastases
      from pancreatic carcinoma are mostly autoptic findings. To our knowledge, this is
      the first case reported in literature of cerebellar metastasis from pancreatic
      cancer; furthermore, this case calls attention on vomit presentation that could
      be erroneously attributed to an abdominal relapse. Due to the increasing
      frequency of central nervous system metastases observed in recent years in other
      types of cancer, some authors speculate that this event could represent a
      consequence of the prolonged natural history as the result of improved survival.

PMID- 16437907
TI  - [Duodenocephalopancreatectomy with pylorus sparing and occlusion of the main bile
      duct with fibrin glue].
AB  - The leakage of pancreaticojejunostomy represents the main technical post
      operative complication after pancreaticoduodenectomy. Because pancreatic fistula
      can be the source of morbidity and mortality and it is related to the integrity
      of the pancreatic-enteric anastomosis, a number of technical modification have
      been suggested, including pancreaticojejunostomy, pancreaticogastrostomy and
      occlusion of the main pancreatic duct with fibrin glue. The incidence of leakage
      is particularly high in case of narrow ducts and tender pancreatic glands; in
      such conditions some experiences in literature suggest the technique of occlusion
      of the main pancreatic duct with fibrin glue.

PMID- 16437908
TI  - [Metastatic malignant melanoma of the pancreas: which strategy?].

PMID- 16437909
TI  - Pancreatic insulinomas: diagnosis and surgical treatment of 45 patients.

PMID- 16437910
TI  - [Positron emission tomography with fluorodeoxyglucose in gastro-entero-pancreatic
      tumors: diagnostic role and prognostic implications].
AB  - From November 1994 to November 2004, seventy-seven patients with neuroendocrine
      gastro-entero-pancreatic tumor (71% pancreatic) were investigated with 18
      fluorine-deoxi-glucose positron emission tomography (FDG-PET). PET results were
      compared with CT-scan, MRI and octreoscan scintigraphy and clinico-pathologic
      features of patients and survival. Overall PET sensitivity was 57%; 78% of
      malignant tumors, 67% of borderline and 17% of benign tumors were detected by FDG
      PET. No duodenal tumor was detected by PET scan. Only 16% of primary less than 2
      cm in size was localized. In 16% of cases PET scan provided new information able
      to change therapeutic management. In PET positive patients the addictive
      information obtained by PET scan when compared with octreoscan, MRI and CT scan
      were respectively 50% more, 26% more and 30% more. In malignant neuroendocrine
      tumors PET positivity was related to short survival. No patient with malignant
      tumor died for disease progression in the follow-up when PET was negative, while
      13/35 PET positive patients died (p <0.003). FDG-PET proved to be a second line
      technique in neuroendocrine digestive tumors. PET results improve clinical
      staging of disease and is related to survival in malignant cases; in 16% of cases
      may change the therapeutic option.

PMID- 16437911
TI  - [Clinical significance and prognostic value of tumor maximum diameter in gastric
      carcinoma].
AB  - Maximum tumor diameter (MTD) is considered by many authors as an important
      prognostic factor in gastric cancer and, in some series, is reported to be
      strongly correlated with depth of infiltration. Aim of this study was to evaluate
      the prognostic value of tumor diameter in a monoistitutional series of 153
      gastric cancer patients. The Spearman correlation coefficient was also calculated
      between MTD and other known prognostic factors. For statistical analysis,
      patients were grouped as follows: MTD 1, < or = 40 mm, and MTD2, > 40 mm. In our
      series, MTD resulted significantly linked to survival at univariate analysis (p =
      0.0001), but multivariate analysis did not evidence MTD as an independent
      prognostic indicator. The Spearman correlation test documented that MTD2 is
      strongly correlated with tumor depth (pT), nodal status (pN) and p-stage (p <
      0.01) and is a good predictor of locally advanced stage. This retrospective study
      showed that patients with larger tumor are at an increased risk for tumor
      advancement and, therefore, MTD could represent a useful parameter for choosing
      the most appropriate therapeutic strategy.

PMID- 16437912
TI  - [Jaundice from neoplastic lymphangitis in patients undergoing D2/3
      lymphadenectomy for gastric neoplasms. Our experience].
AB  - The surgical treatment of gastric adenocarcinoma foresees, toghether with the
      gastric resection, the lymph nodes resection as indicated by the Japanese
      Research Society for Gastric Cancer. Obstructive jaundice, as a consequence of
      lymph nodes metastases, is one of the most debilitating pattern of recurrence. In
      the present paper three cases of jaundice, observed during the follow-up, after
      D2-D3 gastric adenocarcinoma resection, with no evidence of lymph nodes
      recurrence either at the restaging or at the intraoperative esploration are
      reported. We believe that the jaundice etiology, in the present series, could be
      due to neoplastic lymphangites of the biliar wall.

PMID- 16437914
TI  - [Evolution of the treatment of locoregional recurrences of gastric carcinoma].

PMID- 16437913
TI  - [Total esophagogastrectomy with esophago-ileocolon-jejunoplasty: case report].
AB  - In this article, we describe a successfully performed total esophagogastrectomy
      for esophageal carcinoma in young man. The esophagus was mobilized via the right
      thoracotomy. Intestinal continuity, installed isoperistaltically was restituted
      in the same operation using an ileo-colic segment transferred to the left lateral
      cervical aspect by way of the posterior mediastinum. The procedure was used in
      one patient and mortality and complications were nil.

PMID- 16437915
TI  - [Multimodal treatment of gastric MALT lymphoma: our experience].
AB  - Primary gastric lymphoma (PGL) is rare, but its incidence is increasing. It
      represents 52% of all extranodal GI tract lymphomas. The majority of PGLs are B
      cell non-Hodgkin's lymphomas or a high grade, diffuse, large cell lymphoma. The
      development of gastric mucosa associated lymphoid tissue is dependent on
      Helicobacter pylori infection. From January 2000 to February 2004, 10 patients
      were observed in the Unit of Surgical Oncology at Morgagni-Pierantoni Hospital in
      Forli (6 F, 4 M), mean age was 68.3 (range, 45-86). Diagnosis was made in all
      patients by endoscopy and biopsies of gastric mucosa, US endoscopy and TC-PET.
      According to the Ann-Arbor classification modified by Musshoff, 6 patients were
      stage IE(1), 1 IE(2), 1 IIIE. 2 IV. Four and two patients underwent distal or
      total gastrectomy. respectively. Chemotherapy was performed in three patients, RT
      in one patient. Complete remission was observed in patients submitted to surgery
      and chemotherapy alone. No mortality and morbidity were observed. The treatment
      of LGP is not standardized yet. The role of surgery in the treatment of primary
      gastric lymphoma has been recently re-evaluated. Traditionally surgical treatment
      was aggressive, more recently radical gastrectomy is disputed and considered
      unnecessary. Conservative surgery and combined treatment is considered more
      appropriate for localized gastric lymphoma.

PMID- 16437916
TI  - [Sentinel lymph nodes in early gastric cancer: preliminary feasibility study].
AB  - From January to December 2004, 8 patients with pre-operative diagnosis of early
      gastric cancer (EGC) and no nodal involvement were submitted to sentinel node
      biopsy using the dual mapping procedure with endoscopic blue dye and 99mTc radio
      colloid injection. All the patients underwent standard radical gastrectomy and D2
      lymphadenectomy. The resected nodes were evaluated by routine (hematoxylin-eosin)
      histopathological examination; the sentinel (blue or hot) nodes in addition were
      evaluated with immunohistochemistry for cytokeratin. The preliminary results and
      perspectives for feasibility of sentinel node biopsy and its accuracy in
      predicting the nodal status in EGC are discussed.

PMID- 16437917
TI  - [Total gastrectomy extended to the head of the pancreas and the liver with D4
      lymphadenectomy for well-differentiated gastric carcinoma].
AB  - Adenocarcinoma of the stomach is the second most common cancer worldwide. Early
      diagnosis and an adequate surgical approach could save live. Surgical approach is
      conditioned by the extension of the disease and the presence of metastases.
      Extended lymph-node dissection (D2) has been generally accepted as a standard
      treatment modality. However, the role of the super-extended lymphadenectomy (D4)
      for gastric cancer has not been established.

PMID- 16437919
TI  - [Modified surgical technique of pancreas-preserving lymphadenectomy].

PMID- 16437918
TI  - [Gastric hemangiopericytoma: unusual neoplasia but not always benign].

PMID- 16437920
TI  - [Total gastrectomy for gastric cancer: can the type of lymphadenectomy condition
      the long-term results?].
AB  - INTRODUCTION: Gastric cancer is the second tumor for frequency in the world.
      Surgery is still the only curative treatment. Good results in terms of long
      distance survival, postoperative morbidity and mortality have been achieved in
      the last years. The extension of lymphadenectomy is an important and discussed
      matter and it is not clear if lymphadenectomy may contribute to improve the
      surgical results. The Japanese surgeons were the first ones, in the 60's, to
      introduce a D2-D3 extended lymphadenectomy, but the real benefits of this
      technique are still being discussed. Indeed lymphonodal metastasis seem to be one
      of the most important prognostic factors in the gastric cancer and the level and
      the number of metastatic nodes are useful to predict the patients' survival. The
      aim of this study is to value the D2 lymphadenectomy in the patients who were
      treated with total gastrectomy for gastric adenocarcinoma, comparing the results
      both with the D1 lymphadenectomy and the D3-D4, paying attention to the survival
      rates related with the lymphonodal dissection. PATIENTS AND METHOD: From 1998 to
      2004, we studied 87 patients with gastric cancer. Out of 78 patients treated
      surgically, 9 were judged unresectable. Out of 69 patients treated surgically,
      one died before surgery and so he was put away by this study. All the patients
      were treated with total gastrectomy and a GI tract reconstruction by Roux's Y
      termino-lateral esophageal-jejunal anastomosis. In 20 patients we also made a
      splenectomy. We followed the Japanese Research Society for Gastric Cancer
      guidelines, according to which nodes are gathered into 16 levels and divided in 4
      groups (N1-N4) depending on the cancer localization. The extension of the
      lymphadenectomy has been classified according to the level of the removed nods.
      The patients were divided into 3 groups. First group: patients undergone a total
      gastrectomy with D1 lymphadenectomy. Second group: patients undergone D2
      lymphadenectomy. Third group: patients undergone D3 and D4 lymphadenectomy. The
      data we obtained let us value the survival rate. RESULTS: Out of the 78 patients
      treated, 69 were resected with a 88.5% resection rate (69/78). Perioperatory
      mortality was 1.4% (1/69). Global survival was 53.8% (44/68). The 5 years
      survival for the Ia stage was 82.6%, 89.3% for the Ib stage, 67.8% for the II
      stage, 56.6% for the IIIa, 16.8% for the IIIb and 0% for the IV stage. In
      addition the 5 years survival in the patients without lymphnodal metastasis was
      79%, much higher than the 30.6% obtained in the patients with lymphonodal
      metastasis (p <0.0001). In the patients who underwent D1 lymphadenectomy,
      survival was 73.4%, while we obtained a result of 70.4% and 13.8% respectively in
      the D2 and D3-D4 (p <0.05). In the advanced stages (IIIa, IIIb, IV), the survival
      rate in the patients with lymphadenectomy D2 vs D1 vs D3-D4 was 38.9% vs 0% vs
      36.3% (p <0.0001). The survival rate based on the extension of the
      lymphadenectomy in the patients with lymphonodal metastasis resulted to be much
      higher in those patients who underwent a D2 lymphadenectomy (43.5% in 5 years)
      compared both to D1 (0% in 6 months) and (29.5% in 5 years) D3-D4
      lymphadenectomy. CONCLUSIONS: The relation between long distance survival and
      extension of the lymphadenectomy in the patients with gastric adenocarcinoma is
      still being discussed. Different studies show the importance of a careful
      lymphadenectomy as the main mean for a better long distance survival in the
      patients with gastric cancer. Other studies showed a link between gastric cancer
      prognosis and number of positive nodes. If more than 7-8 nodes are affected with
      metastasis, prognosis is usually poor. Therefore the presence of nod metastasis
      has a negative influence in the prognosis of this tumor; for this reason D2
      lymphadenectomy is the technique to be used for the treatment of the gastric
      adenocarcinoma, both for a good staging and a better long distance survival, but
      particularly in the advanced cancers which are, at the moment, the highest number
      of cases that reach the surgeon's attention.

PMID- 16437921
TI  - [Prognostic factors of gastric neoplasms: experience with 1,074 cases undergoing
      surgical treatment at a single center].
AB  - AIM: The aim of our study was to identify clinicopathological predictors of
      survival among patients undergoing potentially curative resections for gastric
      carcinoma. PATIENTS AND METHODS: From January 1987-March 2004, 1074 patients have
      been submitted to curative gastric resection for gastric cancer (647 males and
      427 females, mean age, 65 +/- 12, min 22, max 92). The surgical procedure
      consisted of 289 (27%) total and 785 (63%) subtotal gastrectomies. The extent of
      lymph node dissection was limited D1 (n = 376, 35%) or extended D2 (n = 578, 54%)
      and D3 (n = 12, 1%); no lymphadenectomy was performed in 108 (10%) cases. The
      pathological nodal status has been defined based on the number of involved lymph
      nodes (N1: 1 to 6 positive nodes; N2: 7 to 15 positive nodes; N3: more than 15
      positive nodes). The distribution of N stage was: N0 = 278 (26%), N1 = 344 (32%);
      N2 = 215 (20%); N3 = 129 (12%). Univariate analyses were performed for gender,
      age, pT stage, pN stage, tumor site, tumor size, and extent of lymphadenectomy.
      Significant factors were then entered into a Cox regression analysis. RESULTS:
      The median number of examined lymph nodes was 17 (mean, 18). Overall, 688 (64%)
      of patients had lymph node metastases. Of these patients, the median number of
      involved nodes was 2 (mean, 6). In the univariate analysis age, pT stage, pN
      stage, tumor size, and extent of lymphadenectomy were found to be significant
      factors. In the multivariate analysis T stage, N stage, and extent of
      lymphadenectomy were all independent predictors of survival. The median and mean
      survival time were 69 and 87 months, respectively. Overall survival was 80%, 51%
      and 40% at 1, 5, and 10 years, respectively. CONCLUSIONS: T stage, N stage, and
      extent of lymphadenectomy were all independent predictors of survival in patients
      submitted to curative gastric resections.

PMID- 16437922
TI  - [T-downstaging after neoadjuvant chemotherapy in locally advanced gastric
      carcinoma].
AB  - Only a limited number of trials on neoadjuvant chemotherapy for resectable
      advanced gastric cancer have been planned or conducted up to date, still in
      recent years this treatment strategy has been considered by many the most
      promising tool in order to improve survival of locally advanced tumors of the
      stomach. Aim of this study is to evaluate the clinical significance and the
      possible impact on survival of tumor downstaging after neoadjuvant chemotherapy
      followed by D2-gastrectomy in an accurately staged and thoroughly selected group
      of 30 locally advanced gastric cancer patients, with a complete follow-up of at
      least 3 years. In our series, T-downstaging was observed in 43.3% of patients;
      this parameter, along with other known prognostic factors, was found to be
      significantly associated with survival (p <0.05). Moreover, T-downstaging induced
      by preoperative chemotherapy was significantly associated with absence of
      residual tumor (R0) and no lymph node metastases (ypN0) (p <0.05). At
      multivariate analysis, R0-resection was the only independent prognostic factor
      (HR 9.439, p <0.0001). According to our results we feel encouraged to consider
      neoadjuvant chemotherapy a promising modality for increasing the R0-percentage by
      tumor downstaging.

PMID- 16437923
TI  - [Ratio of lymph node metastasis in gastric carcinoma after D2 gastrectomy].
AB  - The classification of lymph node metastasis in patients with gastric carcinoma is
      controversial. In the past, all systems used for this disease defined N
      classification by the location of lymph node metastases relatively to the primary
      tumor. In the 1997, the UICC and AJCC redefined the pathologic nodal status on
      the basis of the number of involved nodes rather than their location. More
      recently, the ratio between the number of metastatic and the total examined lymph
      nodes has been proposed as a new quantitative staging system. Aim of our study
      was to clarify the outcome of the ratio of the metastatic lymph nodes (RML) in a
      monoinstitutional series of 164 patient with primary gastric cancer who underwent
      gastrectomy with D2 lymph node dissection. Our data showed that ratio of
      metastatic lymph nodes is a simple, convenient, and reproducible staging system
      with an ability to predict surgical results and it is an independent prognostic
      factor after D2-gastrectomy.

PMID- 16437924
TI  - [Lymph node sentinel in gastric carcinoma: proposal of a multicenter GISCRIS
      (Gruppo Italiano per lo Studio della Chirurgia Radioguidata e
      dell'immunoscintigrafia) protocol].
AB  - Sentinel node biopsy has been widely adopted in the treatment of cutaneous
      melanoma and breast cancer. The ongoing controversy concerning the extension of
      lymphatic dissection in gastric cancer demonstrate that the optimal extent of
      lymphadenectomy has yet to be established, and underlines that the research in
      this area is needed to refine our knowledge and consequently our treatment of
      gastric tumors. In this paper the authors describe a multicentric protocol
      concerning the sentinel node research in early and advanced T1-T2 gastric cancer
      employing the blue dye method and lymphoscintigraphy by means of the endoscopic
      injection of Tc99m labeled nanocolloids. The aim of this protocol is to assess
      the clinical relevance of the sentinel node biopsy in selecting N+ patients in
      early gastric cancer, and the role of the same technique in detecting N2 positive
      patients in case of advanced gastric cancer. Assuming a confidence interval of +/
      5%, a sample of 100 recruited cases over three years is previewed.

PMID- 16437925
TI  - [D2 gastrectomy in the surgical treatment of gastric cancer].
AB  - The study is conducted on a series of 57 patients treated with D2 gastrectomy
      with curative intent for gastric cancer between January 2000 and December 2004,
      at Policlinico Multimedica (Milan). Postoperative mortality was 2%. Recurrence
      rate was 10%. The overall survival of the series is 36% at 4 years follow-up.
      Negative prognostic factors were: high grade tumor, locally advanced primary
      disease, presence of lymph node metastases, advanced stage of disease and
      recurrent disease at follow-up. The data of the study are comparable to those in
      the literature.

PMID- 16437926
TI  - [Multiple organ resection in advanced gastric carcinoma: experience of 7 years].
AB  - In this work we report our experience on multiorgan resections (MOR) for local
      advanced gastric cancer. From 1998 to 2004 in our Department 79 patient underwent
      total or partial resection of stomach associated with removal of various other
      organs. The results we report come from the evaluation of perioperative mortality
      and morbidity rates and further analysis of median survival time and quality of
      residual life. In conclusion, we affirm the utility of major surgery in advanced
      gastric cancer only in conditions that guarantee an acceptable rate of major
      complications.

PMID- 16437927
TI  - [Evaluation of prognostic factors in gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumors are relatively rare but have been recently widely
      investigated; the study analyses the role of different prognostic factors on
      disease-free survival after complete resection of tumor.

PMID- 16437928
TI  - [Gastrointestinal stromal tumors: relationship between clinical factors and
      immediate results after resective surgery].
AB  - The impact of different clinical features on surgical strategy and immediate
      results after resection is investigated in a consecutive series of 47
      gastrointestinal stromal tumors.

PMID- 16437929
TI  - GIST: a clinical dilemma.
AB  - The authors report a clinical case of malignant gastric and duodenojejunal GIST,
      in which the only surgical treatment seems to be definitive. In a 69-year-old
      female, a surgical resection of the gastric and duodenojejunal tumor was
      performed. Histological analysis showed two spindle cells stromal tumors with
      mitotic rate >20/10 HPF and its uncommitted origin was demonstrated. Despite the
      high malignancy degree, the patient refused chemotherapy treatment and there were
      no local recurrence nor metastasis at a follow-up of 8 years. For this reason and
      because of the uncertain behavior of histologically benign GIST, the authors
      propose a lifelong follow-up of all patients managed with potentially curative
      surgical resection.

PMID- 16437930
TI  - [Surgical resection of gastrointestinal stromal tumor after treatment with
      imatinib: clinical case].
AB  - The stromal tumor is the most common mesenchymal tumor of the gastrointestinal
      tract. Surgical resection is the first-line therapy for operable lesions, however
      for inoperable imatinib is an effective therapy. In this setting a patient has
      been operated after a remarkable response to imatinib, used as both neoadjuvant
      and adjuvant. This approach led to a disease-free condition without toxicity and
      complications.

PMID- 16437931
TI  - [Gastrointestinal stromal tumors (GIST). Update and indications for treatment:
      our experience].
AB  - The gastrointestinal stromal tumors (GISTs) represent 1% among bowel diseases.
      Their clinical history is unknown, and it seems to develop from muscolar or
      nervous tissue in the bowel wall. The grade of malignancy is directly correlate
      to the dimension of tumor and the number of mythosis for field. We report our
      experience in diagnosis and treatment.

PMID- 16437932
TI  - [Stomach GIST].
AB  - Gastric stromal tumors give diagnostic and therapeutic problems, especially with
      regard to histopathologic identification and biological behavior. These tumors
      are very rare in all case reports. These ones are the most frequent of all
      alimentary tract. They are often incidentally found; because of their potential
      transformation, they have to be treated by respecting oncologic eradication
      standards and observing prognostic criteria based on a correct histopathologic
      evaluation (neoplasm localization and dimension, its structure, presence of
      cytological atypisms, mitotic index, ploidia, surgical resection). Then there has
      to be a good follow-up program.

PMID- 16437933
TI  - [Gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumors (GIST) are generally found in the stomach or
      small intestine and less commonly in the colon or rectum. Complete surgical
      removal remains the best current therapy for GISTs. The treatment of advanced
      GIST patients is with imatinib, a selective tyrosine kinase inhibitor. In our
      series, 23 patients observed between 1994 and 2004 and affected by GIST were
      treated with complete negative margin resections (three cases by laparoscopy).

PMID- 16437934
TI  - [Gastrointestinal stromal tumors: our experience].
AB  - The authors report their experience on the treatment of GIST. They point out the
      importance of classification of the disease in low, medium and high risk
      neoplasms based on the characteristic of the tumour: site, volume and mytotic
      index as the Consensus Conference of Bethesda recently established. Surgical
      procedure remains the most important treatment in localized disease, while
      patients with advanced disease can benefit from imatinib, a chemotherapeutic
      agent recently introduced, as an adjuvant therapy.

PMID- 16437935
TI  - Recurrence rates and long-term follow-up of gastrointestinal stromal tumors.

PMID- 16437936
TI  - [Laparoscopic sleeve gastrectomy for bleeding GIST: clinical case].
AB  - Gastrointestinal stromal tumors (GIST) comprise a rare group of neoplasms of
      unpredictable malignant. The stomach is the most common site of occurrence in the
      gastrointestinal tract. A combination of prognostic factors (patient age,
      histologic grade, mitotic rate, tumor size, and DNA analysis) have been utilized
      to predict their biologic behavior. Lymphatic spread of gastrointestinal stromal
      tumors is uncommon therefore a formal lymph node dissection is not standard
      surgical management. Consequently, complete surgical resection of the primary
      tumor is the most definitive treatment. Although numerous operative approaches
      have been utilized for gastric submucosal tumors, laparoscopic wedge resection
      has been regarded as the treatment of choice in recent years. As widespread use
      of diagnostic endoscopy has exposed a number of gastric submucosal tumors, the
      laparoscopic wedge resections are being performed with increased frequency. In
      this article, we describe a successfully performed laparoscopic sleeve
      gastrectomy for a bleeding GIST.

PMID- 16437937
TI  - Segmental resection of the third and fourth portions of the duodenum after
      intestinal derotation for a GIST: a case report.
AB  - We describe a case in which segmental resection of the third and fourth portion
      of the duodenum was performed for a very rare duodenal gastrointestinal tumor
      (GIST). A 58-year old man presented with melena. Capsule endoscopy revealed a
      pathological bleeding of the duodenum and oral contrast-CT enema confirmed a
      lesion of the duodenum inferior knee, measuring 3.5 cm in diameter. Such an image
      suggested a duodenal leiomyoma. Segmental resection of the third and fourth
      portion of the duodenum after intestinal derotation (Valdoni-Strong's procedure)
      was carried out and there were no post-operative complications. Pancreas sparing
      duodenal resection is at the present time indicated only in selected cases. The
      duodenal resection associated with bowel and right colon derotation has proved to
      be a safe and adequate procedure and could be preferred to other procedures.

PMID- 16437939
TI  - [Peritonectomy and hyperthermic chemoperfusion in peritoneal carcinomatosis.
      Preliminary results].
AB  - BACKGROUND: Peritoneal carcinomatosis can be actually treated by new surgical and
      oncological techniques. Aim of this work is to report preliminary results of a
      group of patients with peritoneal carcinomatosis, submitted to peritonectomy and
      intraperitoneal hypertermic chemoperfusion (IPHC). METHODS: Age, sex, type of
      neoplasm, peritoneal carcinomatosis index (PCI), completeness of cytoreduction
      (CC), operative time, morbidity and mortality of patients submitted to IPHC have
      been considered. RESULTS: From May 2001 to December 2004, 10 patients were
      submitted to peritonectomy and IPHC: 9 (90%) females and 1 (10%) male, aged from
      49 to 72 years. Seven patients (70%) were affected of peritoneal carcinomatosis
      from ovarian tumor, three patients (30%) from colon cancer. The PCI was ranged
      from 8 to 25. The operative time was ranged from 6 to 14 hours. Two patients with
      a CC of 2 developed relaps and died respectively after 2 and 4 months. The
      remaining patients had a CC between 0 and 1. Of these last patients, 1 affected
      by ovarian cancer died 24 months after, 1 patient died 3 days after surgery for
      septic shock; the other patients are still alive with a period ranged from 1 to
      30 months. CONCLUSIONS: Our preliminary results suggest that the peritonectomy
      and IPHC can be effective only in patients with CC of 0 or 1, in the remaining
      cases these therapeutical methods should be avoided.

PMID- 16437938
TI  - [Intraperitoneal chemotherapy with oxaliplatin after complete cytoreduction for
      peritoneal carcinomatosis from colorectal carcinoma: preliminary experience].
AB  - Colorectal cancer with peritoneal carcinomatosis is usually considered incurable.
      Intraperitoneal carcinomatosis accounts for 25-35% of recurrences of colorectal
      cancer. Studies demonstrate that peritoneal carcinomatosis is not necessarily a
      terminal condition with no options for treatment or cure. Encouraging results
      were obtained in many studies by cytoreductive surgery followed by hyperthermic
      intraoperative intraperitoneal chemotherapy (HIIC). Oxaliplatin is a new agent
      whose clinical use with intraperitoneal administration has been pioneered by
      Elias et al. Eight patients with peritoneal carcinomatosis (PC) of colo-rectal
      origin underwent complete cytoreductive surgery from March 2004 to January 2005.
      Six of them were submitted to HIIC with semi-closed technique; in one patient
      mitomycin C (2 mg/m2/l) was used for intraperitoneal perfusion at 41.5-42 degrees
      for 60 minutes; in five patients IPCH was carried out for 30 minutes at 41.5-42
      degrees with intraperitoneal oxaliplatin (460 mg/m2). Patients received
      intravenous leucovorin (10 mg/m2) and 5-fluorouracil (400 mg/m2) just before HIIC
      to maximize the effect of oxaliplatin. Preliminary results are reported.

PMID- 16437940
TI  - [Complications of cytoreductive surgery associated with intraperitoneal
      chemohyperthermia: prevention and treatment].
AB  - New approach to peritoneal carcinomatosis combining cytoreductive surgery and
      hypertermic intraperitoneal chemotherapy suggest improved survival when it is
      possible to achieve a complete cytoreduction. In this study we consider the major
      complications related to this procedure and purpose our approach for their
      prevention and treatment.

PMID- 16437941
TI  - [Cytoreduction and intraoperative peritoneal chemohyperthermia in carcinomatosis
      from colonic carcinoma and in peritoneal pseudomyxoma].
AB  - New approach in treatment of peritoneal carcinomatosis combining cytoreductive
      surgery and intraperitoneal chemotherapy suggests improved survival when it is
      possible to achieve a complete cytoreduction. In this study we consider the
      carcinomatosis from colorectal and appendiceal adenocarcinoma. In all cases,
      patients in whom cytoreductive surgery was complete had a median survival much
      longer compared with patients in whom was not possible and, as perfusion works on
      minimal residual disease, peritonectomy is the only surgical technique that aim
      at total removal of parietal and visceral peritoneal lesions.

PMID- 16437942
TI  - [Integrated treatment of peritoneal carcinomatosis: preliminary experience].
AB  - A prospective study has been carried on 37 patients, 35 of them affected by
      peritoneal carcinomatosis from ovarian (16), appendiceal (7), colorectal (5),
      mesothelial (4), gastric (3) primary and 2 affected by sarcomatosis. Mean PCI was
      22 (median, 22). Eighty-five percent of the patients presented debilitating
      ascites associated in 23% to initial symptoms of intestinal obstruction. All the
      patients have been treated with peritonectomy and intraoperative hyperthermic
      chemoperfusion and CC 0-1 cytoreduction was achieved in 81%. Major morbidity and
      mortality was respectively 37.8% and 16.2%, where 5 out 6 deaths recorded in the
      first 19 months of our experience, representing our learning curve. At a median
      follow-up of 8 months (range, 1-54), 18 patients are alive and disease-free and 4
      patients are alive with disease. Two-yr overall survival was 49.1% for all
      series. Difference in survival evaluating CC 0-1 vs CC 2 patients was
      statistically significant.

PMID- 16437943
TI  - [Peritonectomy and chemohyperthermia in the treatment of peritoneal
      carcinomatosis: learning curve].
AB  - A prospective study has been carried on 37 patients affected by peritoneal
      carcinomatosis from various primary. Patients have been treated by cytoreductive
      surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved
      in 81%. The temperature distribution study showed a "barrier effect" with no
      statistically significant correlation to the survival. Major morbidity and
      mortality was respectively 37.8% and 16.2%. Two-yr overall survival was 49.1% for
      all series. Morbidity was significantly directly correlated to the duration of
      the surgical treatment. A learning curve of 19 months have been observed, after
      that only one death out 21 procedures has been recorded. Peritoneal
      carcinomatosis patients, that are submitted to integrated treatment, need a
      peculiar management that is not comparable to any other in the oncological
      setting and that requires specific competence.

PMID- 16437944
TI  - [Laparoscopic intraperitoneal antiblastic hyperthermic chemoperfusion in the
      treatment of refractory neoplastic ascites. Preliminary results].
AB  - A method of laparoscopic continuous hyperthermic peritoneal perfusion (CHPP) is
      proposed for the treatment of debilitating malignant ascites. The authors report
      14 cases of peritoneal malignancy, not amenable to peritonectomy due to massive
      infiltration of the small bowel. The ascites disappeared in all treated cases.

PMID- 16437945
TI  - [Intraperitoneal hyperthermic chemotherapy. Preliminary experience with 22
      consecutive patients].
AB  - The study analyses the results of surgical treatment and intraperitoneal
      hyperthermic chemotherapy on a group of 22 patients, affected by peritoneal
      carcinomatosis of different origins, and treated at Policlinico Multimedica
      (Milan) between June 2001 and December 2004. Surgical major complications were
      present in the 23% of the patients, and post-operative mortality rate was 13%.
      None of the patients presented chemotherapy related toxicity. Six patients died
      within 2 and 40 months after surgery, while 13 are alive within 4 and 40 months
      after operation.

PMID- 16437946
TI  - [Doxorubicin in antiblastic hyperthermic perfusion in the treatment of advanced
      soft-tissue sarcoma of the limbs].
AB  - Different antineoplastic drugs have been associated to hyperthermia in the
      treatment of advanced soft tissue limb sarcoma with a good results in terms of
      conservative surgery (77%-97%), locoregional control (77%-87%) and overall
      survival (72%). Two different studies were performed: the first was carried out
      to analyze the doxorubicin-TNFalpha-hyperthermia association (three different
      trials) in terms of toxicity and efficacy of the treatment (tumor response,
      locoregional control, disease free and overall survival). The results showed that
      the trimodality association (doxorubicin TNFalpha and hyperthermia) is the best
      regimen able to obtain a 77% of objective response and 77% of limb sparing in
      patients candidate to amputation but may result in high local toxicity if high
      temperatures (>41.5 degrees C) were maintained during perfusion. The second study
      describes the employment of liposomal doxorubicin in hyperthermic antiblastic
      perfusion (HAP) in terms of tumor response, conservative surgery and toxicity;
      the maximum tolerable dose (MTD) of doxorubicin was 16 mg/l of perfused limb
      volume at the temperature of 41.5 degrees C; the conservative surgery was
      possible in 91% of the cases and mild (grade I and II) toxicity was observed in
      the perfused limb with high temperature (>41.5 degrees C).

PMID- 16437948
TI  - [Minimally invasive esophagectomy for adenocarcinoma of the lower esophagus and
      the gastroesophageal junction].
AB  - BACKGROUND: Adenocarcinoma of lower esophagus and GEJ shows worldwide an
      increasing incidence. The optimal approach to resection is still controversial.
      One of the major disadvantages of radical esophagectomy with extensive
      lymphadenectomy with open technique is its high rate of morbidity and mortality.
      Recent advances in minimally invasive surgical technology have allowed surgeons
      to apply laparoscopy and thoracoscopy to perform esophagectomy. PATIENT AND
      METHODS: In the video we report the case of a 79 years old man with Siewert I
      adenocarcinoma of GEJ, who was submitted to a 3-stage minimally invasive
      esophagectomy by laparoscopy, right thoracoscopy and cervicotomy. Preoperative
      endoscopic ultrasound and CT scan showed a marked thickening of the wall of the
      distal esophagus, with extension proximal to the mediastinal pleura and the
      anterior surface of the aorta, but still showing features of resectability. Four
      ports were used for the abdominal approach. A complete mobilization of the
      stomach preserving the right gastroepiploic arcade was achieved. The patient was
      then turned to the left lateral decubitus position proned to 30 degrees. Three
      ports were needed for right thoracoscopy. Mobilization of the thoracic esophagus
      was carried out from the diaphragm to the thoracic inlet. After extraction of the
      specimen through a small abdominal incision, the stomach was pulled up to the
      neck and esophagogastric anastomosis with the Orringer technique was constructed
      through a left cervicotomy. Pathology showed pT3 pN1 G3 adenocarcinoma.
      CONCLUSIONS: The minimally invasive approach to adenocarcinoma of the lower
      esophagus, in center with expertise in minimally invasive surgical technique, is
      feasible and safe.

PMID- 16437947
TI  - [Hemangiopericytoma of the greater omentum. Videolaparoscopic treatment: case
      report and review of the literature].
AB  - Although hemangiopericytoma (HPT) may arise in any anatomic site, it rarely
      develops in the greater omentum. To our knowledge, only twelve cases have been
      reported to date in the English language literature. In this report, we describe
      the case of a patient with sudden severe lower abdominal pain caused by primary
      HPT in the greater omentum treated with laparoscopic approach and a review of the
      reported cases is made.

PMID- 16437949
TI  - [Laparoscopic surgery of adrenal gland metastasis: case report].
AB  - OBJECTIVE: Laparoscopic adrenalectomy is unanimously recognised as the gold
      standard for the surgical treatment of adrenal lesion. Also the role of
      laparoscopic adrenalectomy (LA) for metastasis is controversial. This study, in
      according with literature dates, aimed to confirm that patients are most likely
      to have prolonged survival after resection of adrenal metastases and confirms
      that oncological outcome of laparoscopic adrenalectomy are similar with open
      adrenalectomy. PATIENT AND METHODS: The study included patients who underwent LA
      from 2000 to 2005. Indications for LA were adrenal masses with no radiological
      evidence of involvement of the surrounding structure, or solitary metastases with
      well-controlled primary cancer. The variable evaluated were port-site and intra
      addominal recurrence, distant metastasis and survival time. Primary tumors were
      the followings: lymphoma non-Hodgkin, lung cancer. Patients age was mean 69
      (range, 62-77), the lesions were at right adrenal gland. No conversion to open
      surgery occurred. No complication were observed. Mean operative time was 100
      minutes (range, 90-110). No postoperative complication occurred. Mean diameter of
      the tumor was 4.5 cm (range, 4.2-4.8 cm). Tumor free margins were obtained. Mean
      hospital stay was 3 day. At follow-up mean of ten months (eight-twelve months)
      there was any sight of distant metastases and the patient was alive. CONCLUSION:
      LA seems to be a feasible option if the principles of oncological surgery are
      respected. Adrenalectomy for metastasis, with intent to prolong survival, should
      be offered to patient with favourable tumor biology, such as those with
      significant DFI.

PMID- 16437950
TI  - [Remission of intraoperative complications in videolaparoscopic surgery of the
      colorectum].
AB  - Intraoperative morbidity in the laparoscopic approach for colorectal surgery is
      5.6%. We tried our experience in 4 out of 70 laparoscopic procedures. In 3 cases
      it was dealt with one missed estate of the suture of the rectal stump. Two of
      them were treated with new resection of the rectal stump using in one case the
      opening of the anastomosis. In 1 case of bleeding of a sacral vessel we practiced
      a service 6 cm Pfannestiel incision of 6 cm to handle the hemorrhage.
      Intraoperative morbidity has not modified the course of the postoperative one.

PMID- 16437951
TI  - [Colorectal laparoscopic surgery. Single center experience with 599 cancer
      patients].
AB  - PURPOSE: To analyze the results of laparoscopic colectomy for cancer of colon and
      rectum on early outcome. METHODS: Fifty hundred and ninety-nine consecutive
      unselected patients who underwent laparoscopic colectomy for cancer of the colon
      or rectum between January 1998 and December 2004 in a single Institution were
      prospectively evaluated. Tumor classification was by TNM stage. Patients were
      monitored for postoperative complications for 30 days after surgery. Follow-up
      was done by direct patient contact. RESULTS: Mean (SD) age was 65.8 (11.7) years.
      Mean (SD) ASA score was 2.0 (0.5). The following operations were performed: 248
      left colectomies, 131 right colectomies, 26 sigmoid resections, 164 rectal
      resections, 21 abdominoperineal resections (Miles operation) and 9 total
      colectomies. Conversion rate was 7.2% (43/599 pts). The overall morbidity rate
      was 23.3% (143/599 pts). The mortality rate was 0.3% (2/599 pts). Anastomotic
      leak occurred in 45/599 (7.3%) patients. Re-operation rate was 4.6% (26/599 pts).
      Mean (SD) length of stay was 9.9 (5.8) days. The mean number (SD) of lymphnodes
      intraoperatively collected was 16.7 (9.8). Median (range) time of follow-up
      period was 20.2 months (6-68). One port-site metastasis was found at 18 months
      after surgery. Overall 5-years survival was 81%. Local recurrence rate in
      patients who underwent TME of the rectum was 4.4%. CONCLUSION: Laparoscopic
      colectomies is safe and effective in the treatment of colon and rectal cancer.

PMID- 16437952
TI  - [Laparoscopic liver surgery for metastases of colorectal cancer: analysis of a
      monocentric experience].
AB  - BACKGROUND: Advances in laparoscopic techniques, refinements of instruments and
      growth of practical experience in liver surgery during the last decade have
      prompted some surgeons to develop the laparoscopic approach for hepatic
      metastases of colorectal cancer (MCRC). AIMS: Primary end points of this clinical
      study were safety and effectiveness of laparoscopic hepatectomy for MCRC,
      including early postoperative results and long-term outcomes (overall survival
      and disease-free survival). DESIGN: Retrospective analysis of data
      (clinicopathologic, operative, perioperative ad late results) collected in a
      prospective database. PATIENTS: Between January 1997 and December 2004, 37 non
      consecutive (selected) patients underwent curative laparoscopic hepatic resection
      (n = 42) for MCRC at Montsouris Institut of Paris. Resection was considered when
      all liver metastases can be totally removed with clear margins, and in absence of
      nonresectable extrahepatic diseases. Among them were 24 males and 13 females with
      average ages of 63.4 years (range, 42-78). RESULTS: Metastases were metachronous
      in 18, multiple in 21, bilateral in 12, and <5 cm in diameter in 30. There were
      21 major hepatectomies (n = 3 Couinaud's segments or more), 4 anatomical minor
      resections, and 12 wedge resections. Mean operative time was 324 +/- 105 mins.
      Conversion to laparotomy was necessary in 6 patients (16%), due to massive
      intractable bleeding in 3 patients, multiples adhesions in 1 patient, technical
      reasons (location of the lesion) in 1 patient, and for presence of localized
      carcinosis in 1 patient. Portal triad clamping was performed in 6 patients. Mean
      operative blood loss was 797 +/- 645 ml, and transfusions were required in 4
      patients (11%). Clear resection margins (> 5 mm) were observed in 94%.
      Postoperative mortality was nil. The overall morbidity rate was 35%, with 2 early
      reoperations due to hemorrhage and postoperative ileus. Overall and disease free
      survival at 36 months were 87% and 55%, respectively. Five patients who had a
      recurrence of metastatic liver disease were referred to a second laparoscopic
      resection. CONCLUSION: This clinical study suggests that laparoscopic liver
      surgery for metastatic colorectal cancer can be accomplished safely, in selected
      patients and by experienced surgeons, with good early results and without
      detrimental consequences on survival.

PMID- 16437953
TI  - [Gastrectomy and laparoscopic lymphadenectomy for carcinoma: preliminary
      experience with 59 cases].
AB  - BACKGROUND: Laparoscopic surgery has been used in the treatment of gastric cancer
      with low mortality and morbidity and improvement in patient's quality of life.
      AIM: To evaluate the results of laparoscopic gastric resection. METHODS: A
      retrospective review of 59 patients after laparoscopic surgery for gastric cancer
      was performed. The patients were 31 males and 28 females with a mean age of 67
      (+/- 11) years (min 39, max 90). RESULTS: Tumor stage was IA in 15 patients, IB
      in 10, II in 9, IIIA in 6, IIIB in 9, and IV in 10. In 15 cases the tumor was an
      early gastric cancer. The mean number of dissected lymph nodes was 29 +/-10.
      Conversion rate was 16%. Morbidity rate was 37%. The median length of hospital
      stay was 10 days. Operative mortality was 3%. The mean time of follow-up was 23
      months. Two-year survival was 75%. CONCLUSIONS: Laparoscopic radical total or
      subtotal gastrectomy with extended lymphadenectomy for gastric cancer is a
      feasible, safe, and oncologically effective procedure.

PMID- 16437954
TI  - [Laparoscopic treatment of neoplasms of the body end tail of the pancreas:
      technical notes].
AB  - The authors report a new approach to pancreatic laparoscopic body end tail that
      allows resection for neoplastic disease. This procedure permits en bloc resection
      using endogia 45 without preventive dissection of splenic vessels.

PMID- 16437955
TI  - [Emergencies in colorectal carcinoma: negative prognostic factor?].
AB  - The authors analyze a consecutive series of 219 patients affected by complicated
      colorectal cancer who underwent surgery in emergency. In hospital mortality, 5
      year survival and recurrence's incidence in 104 of these patients who underwent
      curative treatment are calculated and compared with a series of 701 patients who
      underwent elective surgical treatment. There was no significative statistical
      difference between emergency and elective group. At the multivariate analysis
      only the stage of the tumor was an independent prognostic factor.

PMID- 16437956
TI  - Gastrointestinal surgical emergencies in patients treated for hemathological
      malignancies.
AB  - BACKGROUND: Upper and lower gastrointestinal symptoms are major and serious
      complications in patients who undergo chemotherapy for hematological
      malignancies. Their most frequent causes are acute intestinal graft-versus-host
      disease (GVHD) after bone marrow transplant, infections, toxicity or preexisting
      gastrointestinal diseases. Mortality can reach 30-60% of cases. PATIENTS AND
      METHODS: We report 15 cases operated on for abdominal emergencies: 3 severe
      gastrointestinal bleeding and 12 acute abdomen. RESULTS: We performed 10 bowel
      resections, one cholecystectomy, one splenectomy, two laparotomy with pancreatic
      debridement and peritoneal lavage, and one suture of perforated peptic ulcer.
      Operative mortality was 33.3% (5/15). Deaths have been reported only in the group
      of patients with acute abdomen. In all cases death was correlated to generalized
      sepsis related to immunosuppression. CONCLUSIONS: We believe that an aggressive
      approach, consisting of close monitoring and early laparotomy combined with
      vigorous supportive therapy, should be used when dealing with suspected
      gastrointestinal complications in patients with hematological malignancies.

PMID- 16437957
TI  - Results of emergency surgery in patients with Moschowitz's disease refractory to
      hematological treatment: is splenectomy always advisable?
AB  - BACKGROUND: Patients with thrombotic thrombocytopenic purpura (TTP), Moschowitz's
      disease, run a high risk of perioperative bleeding and need intensive hematologic
      support. In some patients, TTP is associated with cancer but the surgical role in
      these patients is still unclear. To illustrate the surgical problems and outcome
      we present the case histories of three patients with TTP observed in our
      emergency department. MATERIALS AND METHODS: Two patients had TTP secondary to
      cancer and one patient with primary TTP (no evidence of neoplasia) had emergency
      operation for gastric hemorrhage, occlusion and TTP unresponsive to
      plasmapheresis. RESULTS: The first two patients who had not radical resection of
      cancer and no splenectomy, died for TTP complications. The third patient who
      underwent emergency splenectomy, had an uneventful postoperative course and TTP
      completely regressed. CONCLUSIONS: These case reports suggest that patients with
      TTP should be screened to rule out cancer. In patients with acute cancer-related
      complications emergency surgery should aim to resect the cancer. An associated
      splenectomy may increase the effectiveness of postoperative hematologic therapy.

PMID- 16437958
TI  - One-stage treatment in emergency setting for obstructing colorectal cancer.
AB  - The aim of this study was to evaluate the indications for one-stage treatment of
      obstructing colorectal cancer. From January 1998 to December 2003, 19 patients
      were operated on at our department for obstructing colorectal cancer. Thirteen
      patients underwent one-stage operation with immediate anastomosis without
      diversion, while 6 patients were managed palliatively. We performed resection and
      anastomosis following intraoperative irrigation in obstructing sigmoid cancer
      without colonic wall lesions, while subtotal colectomy was carried out in case of
      massively distended colon with ischemic lesions. Colostomy was indicated in 6
      high-risk patients with unresectable lesions. In case of obstructing left
      colorectal cancer, an experienced surgeon can perform one-stage resection and
      anastomosis on good general status patients, conversely defunctioning colostomy
      may be ideal for surgeons with little experience in colorectal surgery and in
      very poor prognosis patients.

PMID- 16437959
TI  - Carcinoma of the left colon with obstruction surgical treatment.

PMID- 16437960
TI  - Bowel carcinoid tumors in an emergency setting report of 14 cases.

PMID- 16437961
TI  - [Papillary carcinoma of the thyroid: our experience].
AB  - Papillary carcinoma (PTC) is the most frequently occurring thyroid carcinoma. The
      aim of the present work is to perform a retrospective study to assess 172
      patients with PTC who have been treated surgically, with radium-iodine (except
      microca) and LT4 from 1989 to 1999. The incidence of local, regional and systemic
      recurrence of the disease was verified together with the results at distance.
      Great importance on survival have preoperative cytological diagnosis, radical
      surgery and a modulated radio-iodine therapy. Age and tumor stage have been found
      as major prognostic factors, while no significant difference according to sex has
      been documented.

PMID- 16437962
TI  - [Thyroid microcarcinoma: our experience].
AB  - The thyroid microcarcinoma is definited differentiated carcinoma of max 1 cm in
      diameter. We have reviewed clinical and histopathological results of 54
      consecutive patients with papillary and follicular thyroid microcarcinoma and
      operated in the our clinic in the period 1985 to 2004. Several variables, such as
      older age, multifocality, bilateral disease, and extrathyroidal spread at initial
      assessment, may have some adverse prognostic significance. We recommend total
      thyroidectomy accompanied by modified neck dissection if enlarged nodes are
      diagnosed.

PMID- 16437963
TI  - [Non-endoscopic minimally invasive thyroidectomy in papillary carcinoma. Our
      experience].
AB  - INTRODUCTION: Minimal access thyroid surgery, using various techniques, is
      increasingly being reported. The present study reviews our experience with
      thyroid surgery using a minimally invasive approach in a group of patients with
      papillary thyroid carcinoma. METHODS: A total of 15 female patients with a
      thyroid nodule, not exceeding 2 cm, proven to be a papillary thyroid carcinoma at
      preoperative evaluation, underwent a total thyroidectomy with non endoscopic
      minimally invasive approach. RESULTS: None of the patients presented
      intraoperative central lymphnode involvement. The cytologic preoperative
      diagnosis was confirmed by histology in all cases. One case of transient
      recurrent nerve palsy was observed immediately after surgery. No permanent nerve
      lesions were documented at 4 months. The hospital stay ranged from 48 to 72
      hours. The iodine 131 uptake ranged from 0 to 2.13%, similar to that obtained
      with open thyroidectomy. All patients were satisfied for cosmetic result.
      CONCLUSIONS: The preliminary results of this study showed that non endoscopic
      minimally invasive thyroidectomy could be proposed in patients with T1 papillary
      carcinoma. In our experience the results obtained with this technique are similar
      to that obtained with open thyroidectomy, with the great advantage of a minimal
      neck wound and shorter hospital stay. However a higher number of cases and a
      longer follow-up are needed to confirm the safety of this procedure on the
      management of papillary cancer of the thyroid.

PMID- 16437964
TI  - [Differentiated tumor of the thyroid in children and adolescents].
AB  - Differentiated thyroid carcinoma (DTC) is rare in young patients and represents
      0,5 to 3,0% of childhood carcinomas. The incidence increases with age: a peak
      incidence is observed between 15 and 19 years of age. DTC in children is
      frequently associated with greater risk of cervical lymph node involvement (60
      80% of cases) and lung metastases at diagnosis in 20% of patients. However the
      prognosis for these patients is better when compared with that of adults, despite
      a high incidence of relapse, leading to reoperation. Young age (<16 years), lymph
      node involvement or distant metastases at diagnosis and some histopathologic
      characteristics have been suggested as predictive factors of recurrences. The
      records of 33 patients with DTC in a 14-year period (1990-2004) were reviewed.
      There were 31 females and 2 males who ranged from 11 to 21 years. At the
      diagnosis 15 patients had disease confined to the thyroid, 18 had additional
      lymph node metastases in the neck; one of them had also lung metastases. Total
      thyroidectomy (TT) was the elective approach in all patients (4 cases
      videoassisted). TT was associated to functional neck dissection in 21 cases. 131I
      was administrated to 28 patients (3,7 GBq as ablative dose): 11 of this received
      further radioiodine treatments (mean 7,4 GBq) because of elevated serum
      thyroglobulin levels and presence of loco-regional or lung metastasis at
      diagnostic total body scan after 131I treatment. The overall survival rate was
      100% at a follow up of 4 months to 14 years.

PMID- 16437965
TI  - [Radio-guided surgery in follicular neoplasms of the thyroid].

PMID- 16437966
TI  - 18-FDG PET-CAT scan detection of unknown primary tumor. A case report.

PMID- 16437967
TI  - [Expanders and the prosthetic short line in breast reconstruction after
      mastectomy: experience with the first 130 surgically treated cases].
AB  - Breast reconstruction as now to be consider as a complementary treatment of
      breast cancer surgery. Between 1998-1999 we developed a project of collaboration
      with Polytech-Silimed Europe Gmbh for a new textured tissue expander. This new
      system allows expansion of the middle and lower quadrant of the breast acting a
      physiologic ptosis of the breast. Authors report their experience on the first
      130 patients.

PMID- 16437968
TI  - [Hormone-dependence and C-ERBB2: relationship between estrogen receptor
      expression, estrogen-regulated proteins, and C-ERBB2 in breast carcinoma].
AB  - We reviewed 1491 consecutive cases of operated breast cancer between 1999-2004,
      and found that hormone-dependence, particularly if evaluated with functional
      markers of the estrogen receptor (estrogen regulated proteins, ERP), is inversely
      proportional to antigen neu expression. Our data confirms that ERP can give
      additional information on the probability of response to hormonal therapy.

PMID- 16437969
TI  - [Predictive variables of lymphatic metastasis in breast carcinoma with a diameter
      below 2 cm].
AB  - The axillary lymph node status of patients with newly diagnosed breast cancer
      remains the most important prognostic information available at the moment.
      However, only a minority of patients presents with such node metastases at
      diagnoses. We reviewed our database and studied 500 consecutive patients with
      early breast cancer, and found that age inferior to 50 years, high grade,
      diameter superior to 1 cm, elevated Ki-67, and expression of oncogene p-53 are
      all factors associated with lymph node metastases.

PMID- 16437970
TI  - [Towards the standardization of sentinel lymph node analysis in women with breast
      cancer].
AB  - Sentinel lymph node biopsy allows enhanced pathology through serial sections and
      immunohistochemical analysis of the retrieved node, with detection of
      micrometastases and isolated tumor cells not otherwise recognized. We present our
      experience with a simple, effective, pathology protocol requiring six couples of
      sections at three different sentinel lymph node levels. Additional
      micrometastases or ITC were diagnosed in 51/416 patients (14.6%).

PMID- 16437971
TI  - [Does incidence of sentinel lymph node metastasis increase after diagnostic
      manipulation in women with breast cancer?].
AB  - 503 patients were retrospectively evaluated to assess whether a previous needle
      or core biopsy, or surgical surgical excision of the primary tumor are associated
      with passive dislodgment of tumor cells in the sentinel lymph node, as reported
      in recent publications. We could not identify any increased incidence of sentinel
      lymph node micrometastases or isolated tumor cells after diagnostic manipulation
      of the primary tumor.

PMID- 16437972
TI  - [Strategic approach to immediate breast reconstruction with submuscular-fascial
      tissue expanders].
AB  - Breast reconstruction can be accomplished with implants, autologous tissue or
      both. Thanks to the widespread of microsurgical techniques autologous tissue
      reconstruction has become a frequent option in many departments although it is
      mostly considered a second choice. The aim of this study was to review our
      experience covering the past five years in immediate breast reconstruction with
      tissue expanders. From January 2000 to January 2005 279 patients underwent
      immediate breast reconstruction with submuscular tissue expanders. Tissue
      expander was chosen according to dimension, shape and volume of the healthy
      breast. Operating time, early and late complications, interference with neo
      adjuvant therapies as well as timing and surgical techniques of second-step
      reconstruction were also considered. No major complications occurred. Tissue
      expander, beyond proving itself a valid and safe option in immediate breast
      reconstruction, also decreased the psychological distress following a mastectomy.

PMID- 16437973
TI  - [Role of cutaneous thoraco-abdominal flap in the surgical treatment of advanced
      stage breast tumors].
AB  - Chest wall reconstruction following extensive resection due to advanced breast
      cancer or radionecrosis still represents a challenge for both oncologic and
      reconstructive surgeons. A multitude of techniques including pedicle muscle
      transposition, free muscle flaps and omental flaps have always been considered,
      despite the morbidity of donor site. The authors describe a new cutaneous thoraco
      abdominal flap to cover full thickness defects up to 600 cm2. 16 patients
      underwent chest wall reconstruction with the aforementioned technique. No major
      complications occurred. This technique proved to be a very good options to cover
      large chest wall defects in patients with advanced or recurred breast cancer or
      radionecrosis.

PMID- 16437974
TI  - [Conservative treatment of breast carcinoma in small breasts: new minimally
      invasive surgical technique].
AB  - To achieve satisfactory cosmetic results after breast conserving treatment (BCT)
      of cancer in patients (with small breasts, the association of BCT and bilateral
      video-assisted augmentation mammoplasty with differentiated prosthesis volume was
      performed. From January 2001 21 small breast pts with breast cancer (stage
      T1N0M0) were treated with BCT and immediate trans-axillary video-assisted breast
      reconstruction with differentiated volumes. In 15 patients sentinel node biopsy
      was performed and 6 patients required total axillary dissection. Tumor-free
      margins were confirmed by histological examination. All patients underwent
      postoperative radiotherapy. Cosmetic results were evaluated through 6 parameters:
      breast shape with and without underwear, symmetry, mobility, inframammary fold,
      tenderness. We observed 4 minor complications: seroma3, paresthesia and slight
      arm weakness. Mini-invasive surgical revision was required in 3 cases due to scar
      retraction of the prosthesis pocket. Prosthesis volume resulted 30% (range, 0
      47%) higher in the affected side. Cosmetic result was positive in 85% of cases
      (excellent 15%, good 45%, fair 25%). Trans-axillary video-assisted breast
      mammoplasty with differentiated prosthesis volumes allows to obtain good
      aesthetic results in small breast patients and to extend BCT indications with a
      low morbidity rate.

PMID- 16437975
TI  - [Post-mastectomy breast reconstruction: esthetic-psychological rebalance].
AB  - Patient motivation and desire are the main indications for restoring the breast.
      Breast reconstruction can alleviate the sense of deformity that may develop after
      mastectomy or conservative treatment.

PMID- 16437977
TI  - [Mechanical microanastomosis in reconstructive surgery of the neck and face].
AB  - Aim of the study is to report our preliminar experience with MCA Coupler System
      in mechanical microanastomoses performed in head and neck reconstructive surgery.
      During almost 7 months we performed 7 end-to-end venous anastomoses: 3 of them
      regarding the cephalic district. We had no vascular thrombosis, vascular
      congestion or flap loss. Mean time of execution of anastomosis with MCA Coupler
      System was 10 minutes. In our experence it is essential the choice of the
      appropriate size of the device and a good dissection of recipient vessels. In our
      opinion the Coupler System is an easy applicable device, and an efficient
      alternative to manual micro-anastomoses.

PMID- 16437976
TI  - [Atypical partial tracheolaryngectomy associated with circular pharyngectomy
      followed by flap reconstruction for dedifferentiated papillary carcinoma of the
      thyroid gland].
AB  - The management of the extensive malignancy of the hypopharynx generally combines
      with total laryngectomy. The authors report a case of scanty differentiated
      papillary thyroid carcinoma, extended to the hypopharynx, with partial
      involvement of thyroid, cricoid and first tracheal ring cartilage and unilateral
      vocal fold palsy treated with an "atypical" partial tracheo-laringectomy combined
      with total circular pharyngectomy. The defect has been replaced with an antero
      lateral tight free flap suitably modeled to restore the pharyngeal and laryngeal
      lumen. A modified Montgomery T- tube has been inserted to avoid larynges-tracheal
      stenosis. This unusual technique allowed to restore a stable airway and
      satisfying deglutition and an adequate voice. With this case presentation the
      authors want to subline that when the tumor type is less aggressive than squamous
      cell carcinoma, it is possible to perform a partial larynx preservation also in
      the case of circular pharyngectomy. Obviously the residual laryngeal skeleton
      have to be sufficient to restore laryngeal lumen.

PMID- 16437978
TI  - [Salvage surgery in hypopharyngeal-laryngeal carcinoma: 5-year follow-up].
AB  - The aim of the present study is to evaluate a group of 62 patients with
      ipopharyngo-laryngeal recurrence, pre-treated whit surgery or radiotherapy. All
      of them performed surgical salvage, therefore we analyze the management, the
      results and 5 years follow-up.

PMID- 16437979
TI  - [Five hundred sixty-nine flaps used in reconstruction of the head and neck:
      morbidity analysis and results].
AB  - Aim of the study is to provide high-level results in terms of functionality and
      softness of the tissues achieved with different reconstructive techniques
      performed in oncological surgery of the head and neck. Test group was composed of
      528 patients recovered with a diagnosis of head and neck cancer. We performed 569
      flaps: myocutaneous, cutaneous and fasciocutaneous, and free flaps. The clinical
      outcome and the morpho-functional evaluation show that free flaps can ensure
      excellent results, especially in defined anatomical areas such as the cervical
      esophageal region, jaw and tongue. As to myocutaneous and
      cutaneous/fasciocutaneous flaps, they are still the first reconstructive choice,
      according to their minimal or no functional implications.

PMID- 16437980
TI  - [Reconstruction options after extensive ablation of the mouth].
AB  - Surgical treatment of the advanced tumors of the oral cavity determines
      challenging anatomical and functional defects of the involved districts. The aim
      of our study was to supply reconstructive guidelines for the surgical treatment
      of the tumors of the oral cavity. Indications and conclusions were drawn
      following a retrospective review of data of 76 patients undergone oral and
      oromandibular reconstruction with either pedicled (17) or free flaps (59). The
      analysis included for both groups the registration of type of selected flap,
      success rate, early and late complications rate, functional results at 6 months
      to 1 year, ie oral feeding recovery and quality of oral feeding. The results
      obtained point out that the anatomical and functional complexity of the oral
      cavity needs a wide armamentarium of surgical techniques and skills at prompt
      disposal of the reconstructive surgeon. Free flaps should be kept in mind as the
      first choice for middle-sized to wide defects. An extended range of options in
      this group are available, and the selection should be based on type and extent of
      the defect following surgical oncologic ablation, but also on the surgeon
      experience itself. Pedicled flaps should be alternatively selected on case of
      general, vascular or local contraindications to major free flaps surgery, for the
      higher complications rate and worse functional outcomes to be faced.

PMID- 16437981
TI  - [Decisional algorithm in extended neoplasms of the hypopharynx and the cervical
      esophagus].
AB  - Hypopharynx reconstruction must deal with restoration of not a simple tubed
      conduit but a complex arrangement of constrictive and propulsive forces with fine
      sensory circuits. The chosen surgical approach should guarantee both complete
      removal of tumor and re-establishement of the two primary functions of the
      district: first swallowing and then phonation. We retrospectively reviewed data
      of 67 patients who had undergone oncologic reconstruction of hypopharynx with
      either pedicled or free flaps at the ENT Department of IRCCS Policlinico S
      Matteo, University of Pavia, between November 1994 and July 2004. Type and
      extension of the defect following cancer removal guided the selection of
      reconstructive procedure. Partial defects, with more than 50% mucosa spared, in
      absence of chance of being closed primarly, were covered with radial forearm free
      flaps as first choice; pedicled flaps such as pectoralis major and SCM rotational
      flaps were used instead if free flaps contraindicated by general and/or local
      conditions. With circumferential defects reconstruction was accomplished by means
      of jejunum free flap, as first choice. Adverse local abdominal conditions
      mandated the alternative use of either tubulized or tunnelized fasciocutaneous
      free flaps, such as radial forearm and lateral thigh. When free flaps use
      contraindicated, or in case of salvage surgery after flap loss, pectoralis major
      and latissimus dorsi pedicled flap were chosen. Both reconstructions with free
      and pedicled flaps were successful in an high percentage of cases (>85%).
      Analysis of incidence and causes of flap failure are reported in this work. In
      the free flaps group of patients a lower rate of complications were registered,
      allowing a faster patient discharge from hospital (36% versus 81.3%). An oral
      swallowing function was gained in 92% of free flaps and 62.5% of pedicled flaps.
      Excellent and exclusive oral nutrition (free diet), was obtained in 54% of free
      flaps and 25% of pedicled flaps. None of patients undergone laryngectomy coupled
      in both groups with pharyngectomy achieved an intelligible esophageal speech.
      Only patients in the free flaps group benefitted from voice prosthesis implant:
      in fact this procedure was avoided in pedicled flaps due to the excessive tissue
      bulk. In conclusion, the data collected suggest that free flaps rapresent the
      first choice for both partial and total oncologic hypopharyngeal reconstruction,
      while pedicled flaps should be taken into account when free ones contraindicated
      by general or vascular conditions.

PMID- 16437982
TI  - [Role of salvage surgery in the recurrence of mouth and oropharynx tumors].
AB  - Educational objectives at the conclusion of this presentation, the participant
      should be able to identify the different criteria that lead to the surgical
      approach rather than to the medical treatment (radiation therapy -RT--and/or
      chemotherapy--CT). Introduction. When we have to deal with medium or big
      recurrence of an oral or oropharingeal cancer is very difficult to make the right
      choice between the surgical or medical therapy: what we have to ask to ourselves
      is whether is legitimate to reoperate considering the sequences due to surgery
      and the results expected. Methods. From January 1997 to December 2002 we have
      treated by surgery 135 patients (mean age, 54) with oral and/or oropharingeal
      squamous cell carcinoma (SCC). The percentage of local recurrence was 30% (41/135
      patients) and nodal recurrence was 6% (8/135 pt). Twenty-two/53 patients
      underwent to a salvage surgery; the others 31 patients to a RT and/or CT therapy.
      Conclusion. The overall survival was 29% in surgical patients after 3 years and
      14% after 5; in the other patients the survival was 11% after 3 and 3% after 5
      years. The comparison between the results in case of recurrent cancer of this
      distrect shows that the best approach is the surgery, where is possible; the
      choice is conditioned by the following parameters: the extension of the tumor,
      primary and recurrent; the presence of lymph node or distant metastases; time of
      recurrence; grading and histological characteristics of the tumor and performance
      status of patients.

PMID- 16437983
TI  - [Histophenotypical variants of squamous cell carcinoma of the skin].
AB  - Cutaneous squamous cell carcinoma (SCC) is, in its most frequent presentation, a
      moderately aggressive neoplastic disease. It can, however, present in a moltitude
      of clinico-pathological variants, some of which are characterized by a more
      malignant attitude. It is important to determine which tumors, among the various
      histophenotypes, are high risk in order to establish the appropriate treatment
      and follow-up. Histologic subtype has been considered as a possible variable in
      determining the prognosis of cutaneous SCC. We report our experience with 3 cases
      of peculiar variants of cutaneous SCC.

PMID- 16437984
TI  - [Treatment of skin neoplasms with polidocanol infiltrations. Our experience].
AB  - The authors try to explain the importance of day surgery today. They report their
      5 years experience in treatment of face and neck skin neoplasms by injections of
      a sclerosant product as hydropolyethoxydodecan, in case of a difficult good
      esthetic result with surgery or other therapies because of patients general
      conditions, such as diabetic ones, or because of their viral nature. Then they
      affirm to have treated 350 benign and malign tumors with this method. All
      subjects presented a complete resolution of disease in few weeks and none between
      them controlled has actually complications or recruitment of neoplasm. They
      conclude by saying that this result is probably due to local ischemic reaction
      caused by the substance used.

PMID- 16437985
TI  - False negative and overall survival after sentinel lymph node biopsy in patients
      with cutaneous melanoma.

PMID- 16437986
TI  - [Buschke Loewenstein tumor of the anus-rectum: clinical caseload].

PMID- 16437987
TI  - [Role of lymphadenectomy in the treatment of Merkel-cell tumors in i and ii
      stages].
AB  - Merkel cell carcinoma (MCC) is a rare, malignant skin cancer, exhibiting
      neuroendocrine differentiation, with a significant incidence of locoregional
      lymph nodal involvement (40%-73%). The accepted staging system classifies MCC as:
      stage I, localized skin disease; stage II, regional lymph node disease; stage
      III, metastatic disease. The clinical differentiation of stage I and II patients
      is difficult and understaging is frequent. Surgery, as first approach, represents
      the leading treatment for this neoplasm and, depending on stage consists in:
      local wide excision for stage I patients and local excision and lymphadenectomy
      for stage II. In our experience, lymphadenectomy, included in the initial
      treatment of all stage II patients, seemed to influence positively the prognosis.
      In comparing stage related recurrence and survival rates the results we obtained
      were better in stage II patients, where lymphadenectomy was included in the
      initial treatment than in stage I subjects, who received local excision alone as
      first treatment and lymphadenectomy as secondary treatment for nodal recurrence
      (overall recurrence rate 86% vs 20%, survival rate 71% vs 80% in stage I vs stage
      II patients). The performance of lymphadenectomy for stage I MCC could be
      reconsidered both for a more reliable staging of the disease and for a positive
      impact on recurrence and survival rates.

PMID- 16437988
TI  - [Assessment of the presence of mutations of the epidermal growth factor receptors
      in tumors of various histologies].
AB  - Recent reports from US and Japan have established that mutations in the tyrosine
      kinase (TK) domain of the epidermal growth factor receptor (Egfr) occur in a
      subset of patients with lung cancer that respond to therapy with gefitinib, a TK
      inhibitor. To gain further insights into the role of Egfr in carcinogenesis of
      lung and tumors of diverse histology, that are currently under investigation with
      drugs of the same class, we have taken in examination a panel of tumors
      consisting in 110 pulmonary adenocarcinomas, 40 pulmonary squamous carcinomas, 40
      gastric adenocarcinomas and 40 colorectal adenocarcinomas. The sequence analysis
      of exon 19 and 21 of the Egfr has allowed the identification of 10 cases
      exhibiting specific deletions in exon 19 and 1 case with point mutation in a
      conserved residue in exon 21. All Egfr mutations occur specifically in lung
      adenocarcinomas while tumors of different histology result unaffected. The rate
      of mutation affecting these other tumors is either very rare, involves different
      domains of the receptor or other tyrosine kinases. The molecular analysis of the
      Egfr gene can help identify patients that will benefit from gefitinib therapy.

PMID- 16437989
TI  - [Role of protein p21, p27, and p53 in the prognosis of patients surgically
      treated for gastric cancer].

PMID- 16437990
TI  - [Molecular epidemiologic analysis of the levels of metalloproteases and
      cyclooxygenase-2 in colorectal cancer].
AB  - The aim of this work is the investigation of the level of expression of the
      vascular endothelial growth factor (VEGF) and metalloproteases (such as Cox-2) in
      the colon rectal cancer. The final goal is the correlation with liver metastases.
      Molecular biology approaches will be adopted: in particular: RT-PCR, quantitative
      real time PCR with fluorescent probes, immunolocalizations and Western blotting
      This is a proposal of research. The work is under development and results and
      conclusions cannot be at the moment anticipated. However, in recent publication
      we found human polyomavirus DNA sequences in colorectal tumors.

PMID- 16437991
TI  - [Association of mutations of K-RAS oncogene and deletions of 18Q with lymph node
      metastasis of colorectal cancer].
AB  - Molecular characterization of gastrointestinal cancer has greatly helped the
      definition of the key steps of the malignant transformation process and made it
      the best understood among the malignant cancers. Genetic influences on prognosis
      may have important implications for the management of the disease and help to
      design patient-tailored therapy. In order to acquire additional knowledge on this
      issue we have commenced an institutional study with the aim to identify the most
      frequent molecular alterations and make a correlation with the conventional
      histopathological parameters.

PMID- 16437993
TI  - [Salvage surgery in the treatment of massive abdominal recurrence of uterine
      leiomyosarcoma. Clinical case].
AB  - Uterine leiomyosarcomas carry a dismail prognosis. Diagnosis is often an
      unexpected pathology discovery after hysterectomy for fibroma. Prognosis depends
      on the degree of locoregional extension and thus on early diagnosis. Extended
      surgery in case of relapse is sometimes the only possible approach for symptoms
      control and improvement of quality of life. A case of massive involvement of the
      abdomen by a relapsed uterine leiomyosarcoma treated by extreme surgery is here
      presented.

PMID- 16437992
TI  - [Reconstruction with skin flaps of the posterior aspect of the thighs after total
      pelvic evisceration with removal of vulvo-perineal soft tissues in recurrent
      vulvar squamous carcinoma].
AB  - We report of a case of a fortythree years old women affected by squamous cell
      cancer of the vulva (T3N0M0). Despite curative treatment (radical vulvectomy with
      bilateral inguinal and femoral lymphadenectomy), after 41 months she had a local
      recurrence, retreated with surgery and radiotherapy; another recurrence, after 29
      months was treated with chemotherapy, without results. Because of local diffusion
      with infiltration of the urethra and anus, the patient was submitted to
      demolitive operation (total pelvic evisceratio, excision of pelvic and perineal
      soft tissues and reconstruction with rotating skin flaps of the posterior face of
      the thighs). After two years of follow up, the patient is alive without evidence
      of disease.

PMID- 16437994
TI  - [Xanthogranulomatous pyelonephritis and renal carcinoma. Report of a clinical
      case and review of the literature].
AB  - Xanthogranulomatous pyelonephritis is a rare disease of the kidney; renal
      parenchyma is replaced by lesions radiologically simulating clear cell carcinoma.
      We present a case of a 62-year-old diabetic woman observed at our institution for
      the appearance of back pain and dysuria. A CT scan revealed a large lesion of
      left kidney with psoas muscle infiltration and the patient undrwent a
      nephrectomy. Histology surprisingly showed a xanthogranulomatous pyelonephritis.
      Though recent reports demonstrated the feasibility of conservative management of
      XGP with antibiotics, the use of pre-operative biopsy is still limited by the
      risk of seeding and the high false-negative results. How to distinguish
      xanthogranulomatous pyelonephritis from renal cancer?

PMID- 16437995
TI  - [Pheochromocytoma: role of preoperative diagnosis in the assessment of malignancy
      risk and in the choice of surgical approach].
AB  - Pheochromocytomas are malignant in 5-26% of the cases. Differential diagnosis
      with benign lesions can be difficult even on a pathological basis. Local invasion
      and distant metastasis are the only well established indicators of malignancy. It
      has been reported that the risk of malignancy increases with the lesion size.
      Despite safe laparoscopic adrenalectomy (LA) has been reported for lesions up to
      10 cm, it is considered hazardous for pheochromocytoma larger than 6 cm, because
      of the risk of malignancy and iatrogenic pheochromocytomatosis. We evaluated the
      possibility to pre-operatively recognize pheochromocytomas at risk of being
      malignant that should not be selected for LA. The medical records of all the
      patients who underwent adrenalectomy for pheochromocytoma were reviewed. All the
      preoperatively available data (demographic, clinical, biochemical and
      radiological) were recorded as well as final pathological diagnosis. Comparative
      analysis of patients with benign and malignant pheochromocytomas was performed.
      Sixty-three adrenalectomies for pheochromocytoma were performed in 60 patients.
      Fifty-seven benign and 6 malignant pheochromocytomas were identified. No
      significant difference was found between patients with malignant and benign
      lesions concerning age, gender, family history, symptoms, laboratory and
      radiological findings. In particular, no significant difference was found for
      lesion size between the benign (63.3 +/- 30.6 mm, range, 20-150) and the
      malignant group (48.6 +/- 16.5 mm; range, 30-70). The largest diameter recorded
      for a malignant lesion was 70 mm. No preoperatively available data can reliably
      differentiate between benign and malignant pheochromocytomas. All malignant
      lesions in this series were smaller than 7 cm. Thus, pheochromocytoma size does
      not seem a reliable predictor of malignancy. In absence of the evidence of gross
      local invasion or metastatic disease, LA can be safely proposed also for large
      lesions. Conversion is mandatory in presence of local invasion or difficult
      dissection that could involve inadequate resection.

PMID- 16437996
TI  - [Hysteroscopic diagnosis of cervical involvement in the staging of endometrial
      carcinoma].
AB  - Hysteroscopy could be an interesting approach to evaluate the cervical invasion
      by endometrial cancer. From 2003 to 2004 we performed 30 hysteroscopy with
      endometrial biopsy with conclusive diagnosis of endometrial carcinoma and we
      calculated the sensitivity and specificity of hysteroscopy in assessing tumor
      invasion of the uterine cervix. Our data showed an high sensitivity and
      specificity of hysteroscopy that reported almost the same value of the
      histological examination. Our conclusions are that hysteroscopy is a suitable
      examination in endometrial cancer staging.

PMID- 16437997
TI  - [Artificial nutrition in oncologic surgery: our experience].
AB  - The authors present their experience about the use of artificial nutrition (AN)
      in oncologic surgical patients. They conclude that AN, in particular enteral
      nutrition, should be initiated early in the post-operative period, whenever
      possible, to achieve better results.

PMID- 16437998
TI  - Concurrent radio-chemotherapy with docetaxel and cisplatinum in inoperable or
      relapsed head and neck cancer.
AB  - Usually head and neck cancer is treated with combined therapy, applying surgery,
      if possible, and then radiotherapy and chemotherapy in a sequential or
      concomitant way. Sequential approach seems to be preferred, because of the high
      toxicity rate of concomitant therapy. Platinum compounds and 5-fluorouracil are
      the standard drugs, but new drugs are entering therapeutic arena: gemcitabine and
      taxanes are the most promising ones. The efficacy of these drugs, especially in
      association with radiotherapy, must be assessed; moreover it is essential to
      ascertain how to associate these drugs to radiotherapy and to evaluate drug
      toxicity when combined with the latter. End point of the study here presented is
      a preliminar assessment of toxicity and feasibility of concurrent radio
      chemoterapy with docetaxel and cisplatinum in patients with head and neck cancer.
      The number of enrolled patients and the relatively short time of follow up do not
      allow to evaluate treatment efficacy.

PMID- 16437999
TI  - [Clinical case: multiple synchronous and metachronous cancer].

PMID- 16438000
TI  - Whither AUB? An excursion through the campus lasting five-score years and ten.

PMID- 16438001
TI  - Brief history of cardiac surgery at the American University of Beirut.

PMID- 16438002
TI  - Zuwan--bearded darnel--Lolium temulentum L.--a Middle Age Arab/Islamic anesthetic
      herb.

PMID- 16438003
TI  - Preoperative assessment for non-cardiac surgery: how much is needed?

PMID- 16438004
TI  - A contemporary review of multiple organ failure.
AB  - MOF or MOSF is a serious condition that represents a leading cause of death in
      critically ill or injured patients. It commonly begins as a result of injury,
      widespread inflammation, infection, shock or a combination of the above.
      Progression from SIRS to MOSD and on to MOF can occur within days. Therefore,
      careful systemic monitoring of respiratory, cardiovascular central nervous,
      renal, hepatic, gastrointestinal and hematologic function is vital. Although
      certain mechanisms such as decreased O2 supply to cells, neutrophil priming,
      increased TNF-alpha, interleukins, and NO have been implicated, an effective
      treatment for this condition remains elusive. The anesthesiologist and critical
      care professionals must work together to effectively evaluate and treat the MOF
      patient.

PMID- 16438005
TI  - Auto-PEEP: how to detect and how to prevent--a review.
AB  - Auto-positive end expiratory pressure (auto-PEEP) is a physiologic event that is
      common to mechanically ventilated patients. Auto-PEEP is commonly found in acute
      severe asthma, chronic obstructive pulmonary disease, or patients receiving
      inverse ratio ventilation. Factors predisposing to auto-PEEP include a reduction
      in expiratory time by increasing the respiratory rate, tidal volume or
      inspiratory time. Auto-PEEP predisposes the patient to increased work of
      breathing, barotrauma, hemodynamic instability and difficulty in triggering the
      ventilator. Failure to recognize the hemodynamic consequences of auto-PEEP may
      lead to inappropriate fluid restriction or unnecessary vasopressor therapy. Auto
      PEEP can potentially interfere with weaning from mechanical ventilation. Many
      methods have been described to measure the Auto-PEEP. Although not apparent
      during normal ventilator operation, the auto-PEEP effect can be detected and
      quantified by a simple bedside maneuver: expiratory port occlusion at the end of
      the set exhalation period. The measurement of static and dynamic auto-PEEP
      differs and depends upon the heterogeneity of the airways. The work of breathing
      can be decreased by providing external PEEP to 75-80% of auto-PEEP in patients
      who are spontaneously breathing during mechanical ventilation but there is no
      evidence such external PEEP would be useful during controlled mechanical
      ventilation when there is no patient inspiratory effort. Ventilator setting
      should aim for a prolonged expiratory time by reducing the respiratory rate
      rather than increasing inspiratory flow. Routine monitoring for auto-PEEP in
      patients receiving controlled ventilation is recommended.

PMID- 16438006
TI  - Spontaneous intraoperative hypothermia and cerebral protection in aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND: In patients with aneurysmal subarachnoid hemorrhage (SAH), a trend
      towards cerebral protection has been demonstrated with intraoperative mild
      hypothermia. Mild to moderate spontaneous hypothermia occurs intraoperatively if
      no active measures are taken to warm the patient. The present study investigated
      the cerebral protective role of such spontaneous intraoperative hypothermia in
      patients with aneurysmal SAH. METHODS: In 50 patients undergoing surgery for
      aneurysmal subarachnoid hemorrhage, nasopharyngeal temperatures were monitored
      from the time of endotracheal intubation till the end of surgery. The patients
      were observed for any neurological deterioration during the first 24 h
      postoperatively. The temperatures of the deteriorated and nondeteriorated
      patients, at different stages during surgery, were compared. RESULTS: Ten out of
      the 50 patients showed neurological deterioration within the first 24 h after
      surgery. The nondeteriorated patients had significantly lower nasopharyngeal
      temperatures compared to the deteriorated group at the time of dural opening,
      temporary vessel occlusion (TVO), dural closure and the end of surgery (p < or =
      0.05). They also had a significantly lower temperature for 2 h starting from the
      time of temporary vessel occlusion (p < or = 0.05). When the patients were
      divided into hypothermic (< 34.5 degrees C) and normothermic groups (> 34.5
      degrees C) on the basis of their nasopharyngeal temperature at the time of TVO,
      the normothermic group tended to have a higher incidence of postoperative
      neurological deterioration (p = 0.07). When the aneurysms were classified
      according to their anatomical location, a significant intraoperative temperature
      difference between the deteriorated and nondeteriorated groups was evident only
      in patients with anterior communicating artery aneurysms (p < or = 0.02) and not
      others. Infective complications were more frequent in hypothermic patients (p =
      0.02). CONCLUSIONS: The findings of the current study suggest that mild
      spontaneous intraoperative hypothermia offers cerebral protection in patients
      undergoing surgery for aneurysmal subarachnoid hemorrhage. This protective role
      of seems to be related to the anatomical location of the aneurysm.

PMID- 16438007
TI  - A novel technique for off pump bidirectional Glenn shunt--safety issues--a case
      report.
AB  - A new technique to decompress the superior vena cava (SVC) during off pump bi
      directional Glenn [BDG] shunts is described. Cerebral protection maneuvers and
      the safety concerns of the technique are addressed.

PMID- 16438009
TI  - Anesthetic implications of laparoscopic adrenalectomy in nephrotic syndrome.
AB  - During the last two decades laparoscopic surgery has become a widely practiced
      procedure. Laparoscopic adrenalectomy for adrenal tumor excision is one of these
      new applications. The anesthesia implication are special in the presence of long
      standing essential hypertension and nephrotic syndrome with poly-pharmacy.
      OBJECTIVES: To report on the first anesthesia for laparoscopic adrenalectomy
      Security Forces Hospital (SFH) in Riyadh. SETTING: Tertiary care SFH in Riyadh.
      PATIENT: A 58 year old Saudi woman diagnosed to have essential hypertension,
      nephrotic syndrome, NIDDM, and right adrenal tumor, with the provisional
      diagnosis of pheochromocytoma. INTERVENTIONS: General anesthesia, Thoracic
      epidural, control of hypertension with both alpha and beta blockers, and
      selective SICU admission for monitoring and pain relief. MEASUREMENT AND THE MAIN
      RESULTS: Preoperative ultrasound and MRI, MIBG scan of the adrenals,
      catecholamines serum level, intraoperative direct cardiovascular pressure
      measurements using Swan-Ganz catheter and arterial line. Pain control using
      epidural narcotics, measurement of blood glucose, blood gases, urea, creatinine
      and electrolytes. Adequacy of ventilation monitored by capnography and pulse
      oximetry. The surgical procedure included right adrenalectomy and
      cholecystectomy. CONCLUSION: Anesthesia for laparoscopic adrenalectomy has
      special problems to solve related to the pneumoperitonium effect, poly-pharmacy
      and the current disease state. The use of modern anesthetic agents,
      cardiovascular monitoring, ventilation and proper analgesia make the hospital
      stay short, morbidity and mortality minimal.

PMID- 16438008
TI  - Anesthetic implications for video assisted thoracoscopic thymectomy in myasthenia
      gravis.
AB  - Thymectomy is an established therapy in the management of generalized myasthenia
      gravis (MG). However, the optimal surgical approach to thymectomy has remained
      controversial. There are advocates for transternal, transcervical approaches for
      "maximal" thymectomy. Video-assisted thoracoscopic thymectomy (VATT) presents new
      approach to thymectomy. By minimizing chest wall trauma, VATT not only causes
      less postoperative pain, shortens hospital stay, gives better cosmetic results
      but also leads to wider acceptance by patients for earlier surgery. Anesthesia
      for thymectomy in MG is challenging. Currently we are using non-muscle relaxant
      technique (NMRT) which we adopted in 1994, for maximal thymectomy. In this paper,
      we present our limited experience with two cases of VATT using two different
      NMRTs. Two cases of MG underwent VATT under general anesthesia (GA) and one lung
      ventilation (OLV) using double lumen tube (DLT). In both cases NMRT was used
      which encompass, light GA plus thoracic epidural analgesia (TEA) in one case and
      without TEA in the other case. We believe that the use of NMRT provides good
      operative and postoperative conditions. In this report we have described two
      different NMRTs, one with TEA and the other without. Further studies are needed
      on large number of cases to establish an anesthetic protocol for VATT.

PMID- 16438010
TI  - Pressure measurements during cardiac surgery--internal jugular vs central venous.
AB  - Although central venous pressure (CVP) is a valuable guide and measurement during
      cardiac surgery anesthesia, there are many occasions however, when the time
      consumed in inserting a peripheral catheter, defeats the actual purpose. The
      purpose of this study was to compare central venous pressure and internal jugular
      veins pressure, and to see whether the jugular veins pressures were a reliable
      guide to central venous pressure monitoring. Simultaneous measurements of the
      internal jugular (both left and right side) and right atrial venous pressures
      were made in 70 patients undergoing cardiac surgery both at times when the chests
      were closed and when they were opened. After induction of anesthesia, a 16 gauge
      catheter was inserted into the internal jugular vein on each side of the neck,
      and another catheter was passed into the right atrium. Then the CVP and internal
      jugular veins were measured six times during anesthesia and postoperatively. A
      good correlation was found between pressures of right and left internal jugular
      veins with that of CVP both at times when the chests were closed and when they
      were opened. It is concluded that left and right internal jugular vein pressures
      are reliable guides to central venous pressures during anesthesia in cardiac
      surgery.

PMID- 16438011
TI  - Low central venous pressure anesthesia in major hepatic resection.
AB  - Blood loss and transfusion requirements are major determinants of morbidity and
      mortality following liver resection. This study evaluates the association of low
      central venous pressure [LCVP] with blood loss and blood transfusion during liver
      resection. Thirty consecutive hepatic resections were studied prospectively
      concerning CVP, volume of blood loss and volume of blood transfusion and renal
      outcome. Data were analyzed for those with a CVP < or = 5 mmHg, and > 5 mmHg. A
      multivariate analysis assessed potential confounding factors in the comparison.
      The mean blood loss in patients with a CVP of 5 mmHg or less was < 500 ml and
      that in those with a CVP > 5 mmHg was > 2000 ml. (p <0.001). Only two patients
      with a CVP of < or = 5 mmHg had a blood transfusion whereas 11 patients with a
      CVP > 5 mmHg required transfusion. No incidences of air embolism or permanent
      renal shutdown have been reported. It is concluded that the volume of blood loss
      and blood transfusion during liver resection correlates with the CVP during
      parenchymal transection. Lowering the CVP to less than 5 mmHg is a simple and
      effective technique to reduce blood loss during liver resection and delete the
      need for blood transfusion with its hazards.

PMID- 16438012
TI  - Management of difficult intubation in a patient with ankylosing spondylitis--a
      case report.
AB  - We describe a case of difficult intubation in a patient suffering from ankylosing
      spondylitis undergoing total hip replacement surgery. The anesthetic management
      of 42 year old patient with difficult airway is discussed. Failure of epidural
      anesthesia procedure necessitated general anesthesia. The problems of performing
      awake fibreoptic intubation and other alternative techniques to secure the airway
      are described. Cervical spine involvement in ankylosing spondylitis is of great
      concern for the anesthetist. Longstanding progressive course of this disease
      leads to fibrosis, ossification and ankylosis of entire spine and sacroiliac
      joints. Cervical spine mobility is decreased and in severe cases total fixity
      occurs in a flexed position. Patient may also have atlanto-occipital and temporo
      mandibular joint involvement as well. Cricoarytenoid cartilages involvement may
      result in upper airway compromise. Furthermore cervical spine vertebrae are prone
      to fractures, especially on hyperextension and may lead to spinal cord
      transection and quadriplegia. In this case report we describe the airway
      management of such patient with fixed rigidity of cervical spine and
      thoracolumbar kyphosis.

PMID- 16438013
TI  - Muallem endo-tracheal tube introducer: (METTI)--an aid for the difficult airway.
AB  - This is a brief report evaluating a new single use endotracheal tube introducer
      (METTI) which has a soft curved atraumatic tip. The introducer was tried in 44
      patients, whose direct laryngoscopic view was simulated to Cormack IIIb score,
      and in six patients with real Cormack III score. The overall success rate of
      railroading of the tracheal tube over the introducer was 94% from the first
      attempt.

PMID- 16438014
TI  - Presurgical caudal block attenuates stress response in children.
AB  - BACKGROUND: Our aim was to determine if the anesthesia technique for pain relief
      in children affects the stress response after minor surgery. A rise in blood
      glucose reflects stress-related effects in children who do not receive glucose
      perioperatively. METHODS: Twenty-eight children, ages 17-81 mos, undergoing
      elective urologic procedures, were enrolled. For pain relief, patients received
      presurgical caudal block (group 1), intravenous narcotics (group 2), or
      postsurgical caudal block (group 3). Blood samples were analyzed for glucose
      concentrations immediately after induction of anesthesia at baseline, 15 min
      after surgical incision (second sample), and 30 min after end of surgery (third
      sample). RESULTS: In group 1 there was no change in glucose concentration in the
      second or third samples compared to baseline, while in group 3 there were
      significant increases in those samples, and in group 2 there was a significant
      increase in the second sample compared to baseline. Children in group 1 required
      significantly fewer narcotics in the postanesthesia care unit (PACU), and those
      in group 2 had significantly longer PACU and hospital durations. CONCLUSIONS:
      Presurgical caudal analgesia attenuates the stress response of anesthesia and
      surgery and decreases postoperative narcotic use while narcotics prolong PACU and
      discharge times.

PMID- 16438015
TI  - Tracheal tube obstruction in a case of concealed tracheomalacia--a case report.
AB  - We report on the successful mangement of airway obstruction, immediately after
      tracheal intubation for elective operation, in a patient with concealed
      tracheomalacia. We discuss the issues posed in patients with mild or undiagnosed
      chronic obstructive pulmonary disease (COPD) that are relevant to tracheomalacia.
      We underline the link between tracheomalacia and COPD and emphasize the high
      level of awareness needed, in order to avoid or manage promptly adverse events
      during airway management for anesthesia in these patients.

PMID- 16438016
TI  - Infusion and bolus administration of cisatracurium--effects on histamine release.
AB  - The purpose of this study is to evaluate the usefulness of Cisatracurium Besilat
      (CB), and the method of its administration during laparotomies on adult patients,
      to determine whether CB caused cutaneous, systemic or chemical evidence of
      histamine release. This study was conducted as a randomized, double-blind
      clinical trial on 38 patients (ASA I-II). After a standard anesthetic induction
      with fentanyl and propofol, patients received an i.v. bolus CB (0.15 mg/kg in
      Group A (n=20) or Group B (n=18). In Group B, 0.18 mg/kg/h infusion was started.
      Following reaching stable muscle relaxations for intraabdominal operation and for
      recovery, Group A (Bolus group) and Group B (Infusion group) were compared. Train
      of-four fade during recovery of block were recorded after administration of CB.
      The heart rate and arterial blood pressure were monitored noninvasively. There
      were no significant hemodynamic differences among the groups. 25%-75% spontaneous
      recoveries were (mean+/-s) 12.75+/-4.52, 16.11+/-9.20 minutes for Group A, Group
      B. 70% TOF Ratios were (mean+/-s) 1.07+/-0.13, 1.39+/-0.38 hours for the same
      groups. There was no consistent correlation between hemodynamic changes,
      cutaneous manifestations and histamine concentrations. We conclude that CB does
      not cause systemic or cutaneous histamine release. The infusion method of
      cisatracurium has a stable level of curarization without side effect and there
      were no significant recovery time differences between the groups.

PMID- 16438017
TI  - The effect of premedication on preoperative anxiety.
AB  - The aim of this study was to evaluate the effect of premedication on anxiety,
      cortisol, residual gastric volume and gastric pH. Following the approval of the
      institutional Clinical Research Ethics Committee, 100 patients in ASA I-II
      scheduled for elective gynecologic surgery, were included into a double blind
      study. Patients were randomly allocated into two groups; the placebo and the
      premedicated. Oral 10 mg diazepam in the evening before surgery and 1.5 mg
      midazolam at least 15 min before surgery. The same anesthetic procedure was
      applied for both groups. Anxiety levels of patients were assessed by using
      Spielberger State-Trait Anxiety Inventory Scale (STAIs). Blood samples for
      cortisol measurements were obtained at the preoperative visits, preanesthesia and
      intraoperative phases. Gastric contents were collected through an orally inserted
      gastric tube, acidity was measured by using Merck's pH paper. In placebo group,
      the preanesthetic STAIs values were increased compared to the values obtained at
      preoperative visit (p < 0.001). The preanesthetic STAIs values were decreased in
      premedicated group (p < 0.001). The changes of preanesthetic and preoperative
      visit values were statistically different (p < 0.001). The preanesthetic and
      intraoperative cortisol values were increased in both groups compared to values
      of preoperative visit. The augmentation was significantly higher in the placebo
      group (p < 0.05). Positive correlation was observed between basal state anxiety
      and basal cortisol values and preanesthetic STAIs and cortisol values in the
      placebo group (r = 0.325, p < 0.05). These data support that preoperative
      sedation suppresses the preoperative anxiety and the cortisol augmentation
      resulting from surgery and stress.

PMID- 16438018
TI  - Cardiodynamic monitoring during laparoscopic cholecystectomy.
AB  - With increasing success of laparoscopy, the hemodynamic changes associated
      pneumoperitoneum (PPM) was described using invasive and non-invasive techniques
      with variable results. In the present study, we have used non-invasive
      cardiodynamic monitor to investigate the hemodynamic changes during laparoscopic
      cholecystectomy. Eleven patients who underwent laparoscopic cholecystectomy under
      general anesthesia were studied. Cardiodynamic monitor (thoracic bioimpedance)
      was used to investigate the hemodynamic changes. The following parameters were
      continuously monitored: Heart Rate (HR), mean arterial blood pressure (MAP),
      cardiac output (CO) and cardiac index (CI). For statistical purpose, five phases
      were identified: (A), pre-PPM, (B), 2 min post-PPM, (C), 10 min post-PPM, (D), 30
      min post-PPM, and (E), after gas deflation. SPSS package, Version 9 was used for
      statistical analysis of the data obtained. Student's t-test for paired
      observations was used for comparisons of the mean values of the data obtained,
      where P <0.05 was considered significant. There was significant change of the
      mean value of MAP in phases A and C. Also significant CI changes of the mean
      values was found between stages A and B (P <0.05). The study showed, transient
      cardiac depression immediately after PPM with partial recovery after ten min,
      which was associated with increase in MAP.

PMID- 16438019
TI  - Dietrich Varez, our cover artist, the art and the man.

PMID- 16438020
TI  - Rates of selected birth defects in relation to folic acid fortification, Hawaii,
      1986-2002.
AB  - Because of studies suggesting that folic acid use reduces risk of various birth
      defects, the Unites States fortified enriched cereal grains with folic acid in
      1998. To determine whether this fortification reduced rates for birth defects in
      Hawaii, rates were calculated before and after fortification. Of the 19 birth
      defects categories studied, the rates for 16 were lower after fortification.

PMID- 16438021
TI  - Two cases of Klebsiella pneumoniae primary liver abscesses; an emerging clinical
      entity among diabetics.
AB  - Klebsiella pneumoniae liver abscesses with limited antibiotic resistance have
      been increasing among diabetics in various geographic regions, most notably in
      Taiwan. Two cases of Hawaiian diabetic men with Klebsiella pneumoniae primary
      liver abscesses are presented as well as a brief review of the literature.

PMID- 16438022
TI  - Anomalous inferior Vena cava as the cause of multiple deep venous thrombosis.
AB  - An anomalous Inferior Vena Cava (IVC) is a possible independent risk factor for
      deep vein thrombosis (DVT). This case represents the rare complication of an
      anomalous IVC causing multiple DVTs, not only in the lower extremity, but also in
      the abdominal periaortic circulation. In young patients who develop a DVT without
      risk factors, an anomalous IVC should be in the differential diagnosis.

PMID- 16438023
TI  - The Office of Medical Education.

PMID- 16438024
TI  - Smoking cessation in Hawaii: implications and future directions.

PMID- 16438025
TI  - John Montgomery's legacy: carbocyclic adenosine analogues as SAH hydrolase
      inhibitors with broad-spectrum antiviral activity.
AB  - Ever since the S-adenosylhomocysteine (AdoHcy, SAH) hydrolase was recognized as a
      pharmacological target for antiviral agents (J. A. Montgomery et al., J. Med.
      Chem. 25:626-629, 1982), an increasing number of adenosine, acyclic adenosine,
      and carbocyclic adenosine analogues have been described as potent SAH hydrolase
      inhibitors endowed with broad-spectrum antiviral activity. The antiviral activity
      spectrum of the SAH hydrolase inhibitors include pox-, rhabdo-, filo-, arena-,
      paramyxo-, reo-, and retroviruses. Among the most potent SAH hydrolase inhibitors
      and antiviral agents rank carbocyclic 3-deazaadenosine (C-c3 Ado), neplanocin A,
      3-deazaneplanocin A, the 5'-nor derivatives of carbocyclic adenosine (C-Ado,
      aristeromycin), and the 2-halo (i.e., 2-fluoro) and 6'-R-alkyl (i.e., 6'-R
      methyl) derivatives of neplanocin A. These compounds are particularly active
      against poxviruses (i.e., vaccinia virus), and rhabdoviruses (i.e., vesicular
      stomatitis virus). The in vivo efficacy of C-c3 Ado and 3-deazaneplanocin A has
      been established in mouse models for vaccinia virus, vesicular stomatitis virus,
      and Ebola virus. SAH hydrolase inhibitors such as C-c3Ado and 3-deazaneplanocin A
      should in thefirst place be considered for therapeutic (or prophylactic) use
      against poxvirus infections, including smallpox, and hemorrhagic fever virus
      infections such as Ebola.

PMID- 16438026
TI  - Design, synthesis, and antiviral evaluation of some polyhalogenated indole C
      nucleosides.
AB  - 2,5, 6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB), 2-bromo-5, 6
      dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) and 2-benzylthio-5,6
      dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BTDCRB) are benzimidazole
      nucleosides that exhibit strong and selective anti-HCMV activity. Polyhalogenated
      indole C-nucleosides were prepared as 1-deaza analogs of the benzimidazole
      nucleosides TCRB and BDCRB. A mild Knoevenagel coupling reaction between an indol
      2-thione and a ribofuranose derivative was developed for the synthesis of 2
      benzylthio-5, 6-dichloro-3-(beta-D-ribofuranosyl)indole (12). 3-(beta-D
      ribofuranosyl)-2,5,6-trichloroindole (16) was prepared from 12 in 4 steps. A
      Lewis acid-mediated glycosylation method was then developed to prepare the
      targeted 2-haloindole C-nucleoside 16 stereoselectively in four steps from the
      corresponding 2-haloindole aglycons. Only 12 was active against HCMV but it also
      was somewhat cytotoxic.

PMID- 16438027
TI  - Reaction of the 2'-silyl and 2'-stannyl derivatives of 6
      (bromomethyl)dimethylsilyl-1',2'-unsaturated uridine under radical conditions.
AB  - The mode of cyclization (5-exo versus 6-endo) of 2-sila-5-hexen-1-yl radicals
      generated from 2'-tributylstannyl- and 2'-trimethylsilyl-6
      (bromomethyl)dimethylsilyl-1',2'-unsaturated uridines (8 and 9) was investigated.
      Although the actual structure of the reaction products differ from each other
      reflecting the ease of elimination of the 2'-substituent, it was found that both
      substrates prefer the 5-exo-cyclization pathway.

PMID- 16438028
TI  - Synthetic approaches to nuclease-resistant, nonnatural dinucleotides of anti-HIV
      integrase interest.
AB  - New, nonnatural dinucleotide 5'-monophosphates with a surrogate isonucleoside
      component of L-related stereochemistry, have been synthesized. Structures of the
      target compounds were confirmed by multinuclear NMR spectra (1H, 13C, 31P, COSY),
      UV hypochromicity, FAB HRMS data and X-ray crystallography. These compounds are
      totally resistant to cleavage by 3'- and 5'-exonucleases. Dinucleotides of this
      study with a terminal L-isonucleoside component showed remarkable selectivity for
      inhibition of the strand transfer step of HIV-1 integrase. To the best of our
      knowledge, these compounds represent only the second example of this type of
      selectivity of inhibition of the strand transfer step.

PMID- 16438029
TI  - Stereochemistry of internucleotide bond formation by the H-phosphonate method. 1.
      Synthesis and 31P NMR analysis of 16 diribonulceoside (3'-5')-H-phosphonates and
      the corresponding phosphorothioates.
AB  - Sixteen diribonucleoside (3'-5')-H-phosphonates were synthesized via condensation
      of the protected ribonucleoside 3'-H-phosphonates with nucleosides, and the
      influence of a nucleoside sequence on the observed stereoselectivity was
      analyzed. 31P NMR spectroscopy was used to evaluate a relationship between
      chemical shift and absolute configuration at the phosphorous center of the H
      phosphonate diesters as well as of the corresponding phosphorothioate diesters.
      Although for the most cases such correlation was found, there was however several
      exceptions to the rule where the relative positions of resonances arisingfrom Rp
      and Sp diastereomers were reversed.

PMID- 16438030
TI  - Oligonucleotides containing pyrazolo[3,4-d]pyrimidines: 8-Aza-7-deazaadenines
      with bulky substituents in the 2- or 7-position.
AB  - The synthesis of the 2'-deoxyadenosine analogues 1b, 2b, and 3c modified at the 7
      and/or 2-position is described. The effect of 7-chloro and 2-methylthio groups
      on the duplex stability is evaluated. For that, the nucleosides 1b, 2b, and 3c
      were converted to the corresponding phosphoramidites 15, 19, and 22, which were
      employed in the solid-phase oligonucleotide synthesis. In oligonucleotide
      duplexes, compound 1b forms stable base pairs with dT, of which the separated 1b
      dT base pairs contribute stronger than that of the consecutive base pairs.
      Compound 2b shows universal base pairing properties while its N8 isomer 3c forms
      duplexes with lower stability.

PMID- 16438031
TI  - Nucleoside modification and concerted mutagenesis of the human A3 adenosine
      receptor to probe interactions between the 2-position of adenosine analogs and
      Gln167 in the second extracellular loop.
AB  - Residues of the second extracellular loop are believed to be important for ligand
      recognition in adenosine receptors. Molecular modeling studies have suggested
      that one such residue, Gln167 of the human A3 receptor, is in proximity to the C2
      moiety of some adenosine analogs when bound. Here this putative interaction was
      systematically explored using a neoceptor strategy, i.e., by site-directed
      mutagenesis and examination of the affinities of nucleosides modified to have
      complementary functionality. Gln167 was mutated to Ala, Glu, and Arg, while the 2
      position of several adenosine analogs was substituted with amine or carboxylic
      acid groups. All compounds tested lost affinity to the mutant receptors in
      comparison to the wild type. However, comparing affinities among the mutant
      receptors, several compounds bearing charge at the 2-position demonstrated
      preferential affinity for the mutant receptor bearing a residue of complementary
      charge. 13, with a positively-charged C2 moiety, displayed an 8.5-fold increase
      in affinity at the Q167E mutant receptor versus the Q167R mutant receptor
      Preferential affinity for specific mutant receptors was also observed for 8 and
      12. The data suggests that a direct contact is made between the C2 substituent of
      some charged ligands and the mutant receptor bearing the opposite charge at
      position 167.

PMID- 16438032
TI  - Preference for ribose over deoxyribose in loop-closing base pairs of extra stable
      nucleic acid hairpins.
AB  - We have investigated the effect of switching ribose to deoxyribose at the closing
      base-pair of an extra-stable RNA hairpin. Specifically, we studied the sequence
      5'-GGAC(UUCG)GUCC, a dodecanucleotide that folds into a well-characterized,
      "extra stable" RNA hairpin structure. Recently, we showed that hairpins
      containing a 2',5'-linked (UUCG) loop instead of the native 3',5'-linked loop
      also exhibit extra-stability (Hannoush and Damha, J. Am. Chem. Soc., 2001, 123,
      12368-12374). In this article, we show that the ribose units located at the loop
      closing positions (i.e., rC4 and rG9) contribute significantly to the
      stabilization of RNA hairpins, particularly those containing the 3',5'-UUCG loop.
      Interestingly, the requirement of rC4 and rG9 is more relaxed for DNA hairpins
      containing the 2',5'-UUCC loop and, in fact, they may be replaced altogether
      (ribose--> deoxyribose) without affecting stability. The results broaden our
      understanding of the behavior of highly stable (UUCG) hairpin loops and how they
      respond to structural perturbation of the loop-closing base pairs.

PMID- 16438033
TI  - Synthesis and anti-HCV activity of N9,5'-cyclo-3-(beta-D-ribofuranosyl)-8
      azapurin-2-one derivatives.
AB  - A number of 1- or 6-substituted N9,5'-cyclo-3-(beta-ribofuranosyl)-8-azapurin-2
      one derivatives were synthesized in multi-step reactions. Their anti-hepatitis C
      virus activities were evaluated and some structure-activity relationship is
      discussed.

PMID- 16438034
TI  - Synthesis of 9-[1-(substituted)-3-(phosphonomethoxy)propyl]adenine derivatives as
      possible antiviral agents.
AB  - Acyclic N9 adenine nucleosides substituted at C-1' position were prepared by the
      Mitsunobu reaction of 1-tert-butyldimethylsilyl-4-pivaloylbutan-1,2,4-triol (5)
      with adenine. Pivaloyl hydroxyl was modified to the phosphonomethoxy derivatives,
      and the tert-butyldimethylsilyl hydroxyl was converted to methoxy, azido, amino,
      fluoro, and c-hydroxyethyl and was eliminated to give vinyl. The resulting
      phosphonic acids were converted to prodrugs also.

PMID- 16438035
TI  - Synthesis of 9-[1-(substituted)-2-(phosphonomethoxy)ethyl]adenine derivatives as
      possible antiviral agents.
AB  - Various C-1'-substituted acyclic N9 adenine nucleosides were prepared from 9-[(1
      hydroxymethyl)(3-monomethoxytrityloxy)propyl]-N6-monomethoxytrityladenine. The
      hydroxymethyl was modified to the phosphonomethoxy derivative, and the 3
      monomethoxytrityloxy was converted to hydroxyl, methoxy, azido, and amino. Other
      substituents, such as ethyl and ea-hydroxyethyl were also prepared. The resulting
      phosphonomethoxy derivatives were converted to prodrugs.

PMID- 16438036
TI  - Synthesis of 9-[1-(1 -hydroxyethyl)-3-(phosphonomethoxy)propyl]adenine and
      prodrug as possible antiviral agents.
AB  - The appropriately protected C-1'-hydroxyethyl-3-hydroxypropyl-N9-adenine
      nucleoside was prepared from 1-pivaloyloxy-5-tert-butyldiphenylsilyloxy-3
      pentanol and adenine through the Mitsunobu reaction. One of the terminal
      hydroxyls was converted to the phosphonomethoxy derivative and the prodrug.

PMID- 16438037
TI  - Synthesis of N6-substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives as
      possible antiviral agents.
AB  - A number of N6-substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives
      having hydroxymethyl at C-1' position were prepared from the appropriate 6
      chloroadenine derivative. The syntheses of the corresponding prodrugs of these
      compounds are also reported. These compounds showed poor activity against HCV in
      replicon assay.

PMID- 16438038
TI  - Synthesis and antiviral activity of some 2-substituted 3-formyl- and 3-cyano-5,6
      dichloroindole nucleosides.
AB  - A series of dichlorinated indole nucleosides has been synthesized and tested for
      activity against human cytomegalovirus (HCMV) and herpes simplex virus type-1
      (HSV-1) and for cytotoxicity. The isopropylidene-protected analogs of the
      previously reported 3-formyl-2,5,6-trichloro-1-(beta-Dribofuranosyl)indole
      (FTCRI) and 3-cyano-2,5, 6-trichloro-1-(beta-D-ribofuranosyl)indole (CTCRI) were
      modified by nucleophilic displacement of the 2-chloro substituent using secondary
      amines. Deprotection of the intermediates provided 2-substituted analogs of FTCRI
      and CTCRI in good yield. There was a significant difference in reactivity between
      the isopropylidene-protected and the fully deprotected FTCRI and CTCRI with
      respect to nucleophilic displacement of the 2-chloro substituent using
      dialkylamines. This difference in reactivity was not observed with
      monoalkylamines or with alkoxides, and the corresponding 2-alkylamino- and 2
      methoxy substituted analogs were synthesized from FITCRI and CTCRI directly. None
      of the synthesized analogs demonstrated potent antiviral activity without some
      corresponding cytotoxicity.

PMID- 16438039
TI  - Preparation of nucleoside H-phosphonoselenoate monoesters via the phosphinate
      approach.
AB  - An efficient entry to nucleoside 3'-H-phosphonoselenoate monoesters via
      phosphinate intermediates was developed. It involves a reaction of suitably
      protected nucleosides with triethylammonium phosphinate in the presence of
      pivaloyl chloride, followed by selenization of the intermediate nucleoside
      phosphinates with triphenylphosphine selenide, to produce the corresponding
      nucleoside H-phosphonoselenoates in 86-92% yields.

PMID- 16438040
TI  - Synthetic approaches to a mononucleotide prodrug of cytarabine.
AB  - Synthetic pathways to a mononucleotide prodrug of cytarabine (Ara-C) bearing S
      pivaloyl-2-thioethyl (tBuSATE) groups, as biolabile phosphate protections, are
      reported. Using a common phosphoramidite approach, two different kinds of
      nucleoside protecting groups have been investigated. During this study, we
      observed an intermolecular migration of the Boc protecting group in the course of
      the tert-butyldimethylsilyl ether cleavage using tetrabutyl ammonium fluoride.

PMID- 16438041
TI  - 2',3'-dideoxynucleoside 5'-beta, gamma-(difluoromethylene) triphosphates with
      alpha-P-thio or alpha-P-seleno modifications: synthesis and their inhibition of
      HIV-1 reverse transcriptase.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are prodrugs which require
      three intracellular phosphorylation steps to yield their corresponding,
      biologically active, nucleoside triphosphate. In order to circumvent this often
      inefficient phosphorylation cascade, a plausible approach is to provide the
      active species directly in the form of a stabilized nucleoside triphosphate
      mimic. We have previously shown that such a mimic, namely 5'-alpha-Rp-borano
      beta,gamma-(difluoromethylene)triphosphate (5'-alphaBCF2TP) is a generic
      triphosphate mimic that is biologically stable and can render antiviral ddNs with
      potent inhibitory activity against HIV-1 RT. Herein we report the synthesis and
      activity against HIV-1 RT of several ddN 5'-alpha-modified
      beta,gamma(difluoromethylene)triphosphate mimics with either a non-bridging
      calphaP-thio (5'-alphaSCF2TP) or alpha-P-seleno (5'-alpha SeCF2TP) modification.
      One compound, namely, AZT-5'-alpha-P-seleno-beta,gamma
      (difluoromethylene)triphosphate (diastereomer I), was identified as a potent
      inhibitor of HIV-1 RT (Ki = 64 nM) and represents the first report of HIV-1 RT
      inhibition data for a nucleotide bearing an alpha-P-seleno modification. These
      triphosphate mimics may be useful in the investigation of enzyme mechanism and
      may have interesting properties with respect to drug resistance and polymerase
      selectivity.

PMID- 16438042
TI  - Nucleotides. LXXIV synthesis of alpha-D-arabino-oligonucleotides.
AB  - The 5 alpha-D-arabinofuranosylnucleosides alpha-araU (15), alpha-araT (18), alpha
      araC (22), alpha-araA (25), and alpha-araG (28) have been synthesized by the
      modified silyl-method. The amino groups at the nucleobases and the 2'-hydroxy
      group at the sugar moiety were protected by the 2-(4-nitro-phenyl)ethoxycarbonyl
      (npeoc) group (37-40) and the amide function in alpha-araG was additionally
      blocked by the 2-(4-nitrophenyl)ethyl group (63) to improve solubility in organic
      solvents. Mono-and dimethoxytritylation of the 5'-OH group was performed in the
      usual manner to give 41-48, 64, and 65 in high yields and further substitution of
      the 3'-OH group led to the monomeric building blocks 66-75 as well as the 3'-O
      succinoyl derivatives 76-85 functioning as starting units in solid-support
      oligonucleotide synthesis. A large number of oligo-alpha-arabinonucleotides have
      been prepared on modified CPG-material applying the npeoc/npe strategy as a very
      efficient synthetic tool for highly purified, homogenous oligomers.
      Hybridizations between alpha-arabinonucleotide strands revealed in analogy to
      earlier findings an antiparallel orientation whereas the combination of an oligo
      alpha-D-arabinonucleotide with a complementary oligo-2'-deoxy-beta-D
      ribofuranosylnucleotide showed base-pairing only if a parallel polarity was
      present. The advantages in oligo-alpha-arabinonucleotide synthesis were
      furthermore demonstrated by the synthesis of the talpha-ANA(his) structural
      analog of the natural tRNA(his) of the phage T5.

PMID- 16438043
TI  - Synthesis and anti-HIV activity of beta-D-3'-azido-2',3'-unsaturated nucleosides
      and beta-D-3'-azido-3'-deoxyribofuranosylnucleosides.
AB  - Since the discovery of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-didehydro-2',3'
      dideoxythymidine (d4T) as potent and selective inhibitors of the replication of
      human immunodeficiency virus (HIV), there has been a growing interest for the
      synthesis of 2',3'-didehydro-2',3'dideoxynucleosides with electron withdrawing
      groups on the sugar moiety. Here we described an efficient method for the
      synthesis of such nucleoside analogs bearing structural features of both AZT and
      d4T The key intermediate, 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3-deoxy-D
      ribofuranose, 5 was synthesized from commercially available D-xylose in five
      steps, from which a series of pyrimidine and purine nucleosides were synthesized
      in high yields. The resultant protected nucleosides were converted to target
      nucleosides using appropriate chemical modifications. The final nucleosides were
      evaluated as potential anti-HIV agents.

PMID- 16438044
TI  - An efficient alternative route to 3,6-disubstituted-furo[2,3-d]pyrimidin-2-one
      analogues.
AB  - Copper(I)-catalyzed 5-endo-dig cyclizations of 5-(alkyn-1-yl)uracil derivatives
      had given poor yields of substituted furo[2,3-d]pyrimidin-2-ones unless the
      uracil ring was substituted at N1 with alkyl or glycosyl groups. This limited
      flexibility for the synthesis of analogues with varied substituents at N3 and/or
      C6 of the furo[2,3-d]pyrimidin-2-one core has been overcome with 5-(3
      hydroxyalkyn-1-yl)uracil compounds with no substituent at N1. Manipulation of the
      side-chain hydroxyl group gives access to additional furo[2,3-d]pyrinmidin-2-one
      analogues.

PMID- 16438045
TI  - The middle to 3' end of the HIV-1 vif gene sequence is important for vif
      biological activity and could be used for antisense oligonucleotide targets.
AB  - The human immunodeficiency virus type-1 (HIV-1)-encoded vif protein is essential
      for viral replication, virion production, and pathogenicity. HIV-1 Vif interacts
      with the endogenous human APOBEC3G protein (an mRNA editor) in target cells to
      prevent its encapsidation into virions. Some studies have established targets
      within the HIV-1 vif gene that are important for its biologic function; however,
      it is important to determine effective therapeutic targets in vif because of its
      critical role in HIV-1 infectivity and pathogenicity. The present study
      demonstrates that virions generated in transfected HeLa-CD4+ cells, especially
      from HIV-1 vif frame-shift mutant (3' delta vif; 5561-5849), were affected in
      splicing and had low infectivity in MT-4 cells. In addition, HIV-1 vif antisense
      RNA fragments constructed within the same region, notably the region spanning
      nucleic acid positions 5561-5705 (M-3'-AS), which corresponds to amino acid
      residues 96-144, significantly inhibited HIV-1 replication in MT-4 and reduced
      the HIV-1 vif mRNA transcripts and reporter gene (EGFP) expression. The generated
      virions showed low secondary infection in H9 cells. These data therefore suggest
      that the middle to the 3' end of vif is important for its biological activity in
      the target cells.

PMID- 16438046
TI  - Phosphoralaninate pronucleotides of pyrimidine methylenecyclopropane analogues of
      nucleosides: synthesis and antiviral activity.
AB  - The Z- and E-thymine and cytosine pronucleotides 3d, 4d, 3e, and 4e of
      methylenecyclopropane nucleosides analogues were synthesized, evaluated for their
      antiviral activity against human cytomegalovirus (HCMV), herpes simplex virus 1
      and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV),
      human immunodeficiency virus type 1 (HSV-1), and hepatitis B virus (HBV) and
      their potency was compared with the parent compounds 1d, 2d, 1e, and 2e. Prodrugs
      3d and 4d were obtained by phosphorylation of parent analogues 1d or 2d with
      reagent 8. A similar phosphorylation of N4-benzoylcytosine methylenecyclopropanes
      9a and 9b gave intermediates 11a and 11b. Deprotection with hydrazine in pyridine
      acetic acid gave pronucleotides 3e and 4e. The Z-cytosine analogue 3e was active
      against HCMV and EBV The cytosine E-isomer 4e was moderately effective against
      EBV.

PMID- 16438047
TI  - A novel imidazole nucleoside containing a diaminodihydro-S-triazine as a
      substituent: inhibitory activity against the West Nile virus NTPase/helicase.
AB  - The attempted synthesis of a ring-expanded guanosine (1) containing the
      imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2'-deoxy-beta-D
      erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with
      guanidine resulted in the formation of an unexpected product, 1-(2'-deoxy-beta-D
      erythropentofuranosyl)-5-(2, 4-diamino-3, 6-dihydro-1,3, 5-triazin-6-yl)imidazole
      4-carboxamide (7). The structure as well as the pathway of formation of 7 was
      corroborated by isolation of the intermediate, followed by its conversion to the
      product. Nucleoside 7 showed promising in vitro anti-helicase activity against
      the West Nile virus NTPase/helicase with an IC50 of 3-10 microg/mL.

PMID- 16438048
TI  - Nucleosides and nucleotides. 232. Synthesis of 2'-C-methyl-4'-thiocytidine:
      unexpected anomerization of the 2'-keto-4'-thionucleoside precursor.
AB  - The synthesis of 2'-C-methyl-4'-thiocytidine (16) is described. Since the 2'-keto
      4'-thiocytidine derivative 2beta unexpectedly isomerized to 2alpha and the
      methylation of 2beta proceeded predominantly from the less hindered alpha-face to
      give 7, the desired product 16 was synthesized via the Pummerer reaction of the
      sulfoxide 14 and N4-benzoylcytosine.

PMID- 16438049
TI  - Binding of G-quadruplex-interactive agents to distinct G-quadruplexes induces
      different biological effects in MiaPaCa cells.
AB  - Our previous studies have demonstrated the preference of telomestatin for
      intramolecular, rather than the intermolecular, G-quadruplex structures, while
      TiMPyP4 has selectivity for intermolecular over intramolecular G-quadruplex
      structures. However, it was not clear whether the difference in the selectivity
      between two different G-quadruplex-interactive agents could determine the
      corresponding biological effects in cultured human tumor cells. Here we evaluated
      the biological effects of both TMPyP4 and telomestatin in the human pancreatic
      carcinoma cell line (MiaPaCa) using subtoxic and cytotoxic concentrations. The
      cytotoxicity of these agents against MiaPaCa cells is quite different, and the
      IC50 of telomestatin (0.5 microM) is about 100 times less than that of TMPyP4 (50
      microM). At IC50 concentrations, TMPyP4 induced anaphase bridge formation in
      MiaPaCa cells, while telomestatin failed to induce anaphase bridge formation. At
      subtoxic concentrations, TMPyP4 induced MiaPaCa cell growth arrest, senescence,
      apoptosis, and telomere length shortening within 5 weeks, while similar
      biological effects were evident after 12 weeks following treatment with
      telomestatin. Our data suggest that binding of G-quadruplex-interactive agents to
      distinct G-quadruplexes could induce different biological effects in human cancer
      cells.

PMID- 16438050
TI  - Synthesis and pharmacokinetic and pharmacodynamic evaluation of the forodesine
      HCl analog BCX-3040.
AB  - Forodesine HCl is a potent inhibitor of the enzyme purine nucleoside
      phosphorylase (PNP) and is currently in clinical trials for the treatment of
      leukemia and lymphoma. Animal models indicated that forodesine HCl would have low
      oral bioavailability in humans and it was initially developed as an intravenous
      formulation. We were interested in identifying analogs of forodesine HCl with
      improved oral bioavailability. The 2'-deoxy analog (BCX-3040) was synthesized and
      its pharmacokinetic and pharmacodynamic properties compared with forodesine HCl.

PMID- 16438051
TI  - Synthesis of a convenient thymidine glycol phosphoramidite monomer and its site
      specific incorporation into DNA fragments.
AB  - An original phosphoramidite building block of the thymidine glycol lesion has
      been prepared taking into account the additional diol function and the high
      lability of this oxidatively induced nucleobase damage. Then the modified
      nucleoside was site-specifically inserted into DNA fragments by solid support
      assembling followed by a "one-step" mild final deprotection treatment.

PMID- 16438052
TI  - 2'-MeO-RNA containing oligodeoxyribonucleotide primers can prevent template
      independent base extension on microarrays.
AB  - DNA microarrays require tens of thousands of deoxyoligonucleotides to be
      registered in an addressable fashion through immobilization, so that they have
      the high-throughput capability of analyzing a large number of samples
      simultaneously in a minimal volume of each reagent. However, using immobilized
      DNA molecules on microarrays can impose certain technical problems for some
      assays. For example, high background noise has been observed in using immobilized
      oligonucleotide microarrays (DNA chip) for primer extension reactions. This noise
      may be associated with the reactions of secondary structures formed by the
      adjacent primers physically constrained on the surface. Single-base extension
      (SBE) of arrayed primers on a chip has been extensively used in mini-sequencing
      to examine single nucleotide polymorphisms (SNP). Some primers appeared to be
      extendable in the absence of any template and thus competed against the base
      extension directed by. the assay target such as genomic DNA. In this article, a
      method is reported that is capable of reducing template-independent extension by
      the substitution of a 2'-methoxyribonucleotide in the otherwise
      oligodeoxyribonucleotide primer. The surrogate compound placed at the 5'-end of
      the putative secondary structure sequence of a given primer was able to inhibit
      template-independent extension and to improve data quality of surface-attached
      primer extension assays.

PMID- 16438053
TI  - Synthesis and application of negatively charged PNA analogues.
AB  - Negatively charged DNA mimics containing phosphonate analogoues of peptide
      nucleic acids were designed, and their physicochemical and biological properties
      were evaluated in the comparison with natural oligonucleotides, classical peptide
      nucleic acids, and morpholino phosphorodiamidate oligonucleotide analogues. The
      results obtained revealed a high potential of phosphonate-containing PNA
      derivatives for a number of biological applications, such as diagnostic, nucleic
      acids analysis, and inhibition of gene expression.

PMID- 16438054
TI  - Confocal microscopy studies of a model oligoribonucleotide HIV inhibitor.
AB  - Previous work has shown that novel amphipalhic oligo and polyribonucleotides are
      potent inhibitors of HIV. It was hypothesized that the mechanism(s) of action for
      these compounds might be inhibition of retroviral reverse transcriptase (RT)
      and/or viral uptake by cells. A fluorescent oligonucleotide analog was prepared,
      and confocal microscopy studies were undertaken in order to examine
      oligonucleotide-cell interactions.

PMID- 16438055
TI  - Double-headed acyclo C-nucleoside analogues. Functionalized 1,2-bis-(1,2,4
      triazol-3-yl)ethane-1,2-diol.
AB  - Reaction of L-tartaric acid with thiocarbohydcrazide afforded (1R, 2S)-1,2-bis(4
      amino-5-mercapto-1,2,4-triazol-3-yl)-ethane-1,2-diol (3). The functional groups
      in 3 allowed the construction of fused heterocycles on the 1,2,4-triazole rings,
      mainly of the 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine type as in 4, 5, 7, 10, 13
      and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole type as in 14.

PMID- 16438056
TI  - Synthesis and biological activity of 4'-thio-L-xylofuranosyl purine nucleosides.
AB  - A series of some new 4'-thio-L-xylofuranosyl nucleosides were prepared and
      evaluated as potential anticancer agents. A versatile sugar intermediate for
      direct coupling with the purine moiety is also synthesized by an efficient and
      high-yielding route. Proof of structure and configuration at all chiral centers
      of the nucleosides was obtained by proton NMR. All target compounds were
      evaluated in a series of human cancer cell lines in vitro. The details of the
      synthesis of the carbohydrate precursor 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-L
      xylofuranose (6) and corresponding purine nucleosides are presented in the
      manuscript.

PMID- 16438057
TI  - Suppression of human immunodeficiency virus type 1 (HIV-1) replication by an HIV
      1-dependent double locked vector with the Cre/loxP system.
AB  - We previously demonstrated the function of an HIV-1-dependent ribozyme expression
      vector, with which the site-specific excision of loxP sequences can be achieved
      by using the Cre-loxP system (ON/OFF) as a molecular switch in an acute HIV-1
      infection. However, this expression system also revealed the lower, non-specific
      expression of the anti-H1V-1 ribozyme in the absence of tat. To circumvent this
      problem, we used the more efficient HIV-1-dependent Cre recombinase gene
      expression vector, encoding the LTR-gag-p17 (extending from the 5'-LTR to the
      middle of the gag gene (pLTR-gag-p17-Cre)). Comparatively, the pLTR-gag-p17-Cre
      induces a higher Cre-protein expression level in an HIV-1 infection-dependent
      manner than the minimal pLTR-Cre. Furthermore, we constructed the ploxP-Rz-U5 and
      pLTR-gag-p17-Cre plasmids and also combined them into a single vector, pLTR-gag
      p17-Cre/loxP-Rz-U5, for a comparison of their anti-HIV-1 activities. The
      resultant simultaneous expression of the Cre protein and the homologous
      recombination of the two loxP sequences induced a high level of HIV-1 replication
      inhibition (95%). Significantly, a high steady-state of ribozyme expression was
      observed in the RT-PCR analysis. These data imply that targeting the HIV-1 genes
      with the pLTR-gag-p17-Cre/loxP-Rz-U5 vector, which mediates HIV-1-dependent
      ribozyme expression, would be a useful tool for HIV-1 gene therapy applications.

PMID- 16438058
TI  - Synthesis and structural analysis of oxadiazole carboxamide deoxyribonucleoside
      analogs.
AB  - Two novel C-linked oxadiazole carboxamide nucleosides 5-(2'-deoxy-3',5'-beta-D
      erythro-pentofuranosyl)-1,2,4-oxadiazole-5-carboxamide (1) and 5-(2'-deoxy-3',5'
      beta-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-3-carboxamide (2) were
      successfully synthesized and characterized by X-ray crystallography. The
      crystallographic analysis shows that both unnatural nucleoside analogs 1 and 2
      adapt the C2'-endo ("south") conformation. The orientation of the oxadiazole
      carboxamide nucleobase moiety was determined as anti (conformer A) and high anti
      (conformer B) in the case of the nucleoside analog 1 whereas the syn conformation
      is adapted by the unnatural nucleoside 2. Furthermore, nucleoside analogs 1 and 2
      were converted with high efficiency to corresponding nucleoside triphosphates
      through the combination chemo-enzymatic approach. Oxadiazole carboxamide
      deoxyribonucleoside analogs represent valuable tools to study DNA polymerase
      recognition, fidelity of nucleotide incorporation, and extension.

PMID- 16438059
TI  - Solid-phase parallel synthesis of 4-beta-D-ribofuranosylpyrazolo[4,3-d]pyrimidine
      nucleosides.
AB  - The synthesis of pyrazolo[4,3-d]pyrimidine nucleoside library using solid-phase
      parallel synthesis methodology is described. Glycosylation of the trimethylsilyl
      (TMS) derivative of 1- and 2-(methyl)-1H and 2H-pyrazolo[4,3-d]pyrimidine-5,7
      (4H, 6H)-dione (5) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the
      presence of TMS triflate provided two novel protected nucleosides 6 and 7. The
      structures of 6 and 7 were assigned by 1H and 2D NMR experiments. Nucleosides 6
      and 7 were then transformed to the key intermediates 12 and 15 respectively.
      Reaction of 12 and 15 with MMTCl resin in the presence of 2,6-lutidine afforded
      the necessary scaffolds B and C. Different amines (96) were introduced
      selectively by nucleophilic substitution on scaffolds B and C using solid-phase
      parallel semi-automated synthesizer. Cleavage of the products from the solid
      support with 30% HFIP in a parallel fashion yielded nucleoside libraries
      simultaneously, and they were analyzed and characterized by high-throughput LC
      MS.

PMID- 16438060
TI  - Synthesis of 3-aminoimidazo[4,5-c]pyrazole nucleoside via the N-N bond formation
      strategy as a [5:5] fused analog of adenosine.
AB  - 3-Amino-6-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an
      N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A
      series of 5-amino-1-(5-O-tert-butyldimethylsilysilyl-2,3-O-isopropylidene-beta-D
      ribofuranosyl)-4-(1,2,4-oxadiazol-3-yl)imidazoles (6a-d), with different
      substituents at the 5-position of the 1,2,4-oxadiazole, were synthesized from 5
      amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was
      found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-beta-D
      ribofuranosyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)imidazole (6a) underwent the MHR
      with sodium hydride in DMF or DMSO to afford the corresponding 3
      acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7b and/or 7a) in good yields. A
      direct removal of the acetyl group from 3-acetamidoimidazo[4,5-c]pyrazoles under
      numerous conditions was unsuccessful. Subsequent protecting group manipulations
      afforded the desired 3-amino-6-(beta-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2)
      as a 5:5 fused analog of adenosine (1).

PMID- 16438061
TI  - Pyrimidine and purine analogues, effects on cell cycle regulation and the role of
      cell cycle inhibitors to enhance their cytotoxicity.
AB  - In anti-cancer treatment, deoxynucleoside analogues are widely used in
      combination chemotherapy. Improvement can be achieved by rational design of novel
      combinations with cell cycle inhibitors. These compounds inhibit protein kinases,
      preventing the cell cycle from continuing when affected by deoxynucleoside
      analogs. The efficacy is dependent on the site of cell cycle inhibition, whether
      multiple cyclin-dependent kinases are inhibited and whether the inhibitors should
      be given before or after the deoxynucleoside analogs. The action of cell cycle
      inhibition in vivo may be limited by unfavorable pharmacokinetics. Preclinical
      and clinical studies will be discussed, aiming to design improved future
      strategies.

PMID- 16438062
TI  - Ribose-modified mizoribine analogues: synthesis and biological evaluation.
AB  - Synthesis, conformational analysis and antitumor evaluation of 2'- and 3'-C
      methyl analogues of mizoribine (bredinine, 4-carbamoyl-1-beta-D
      ribofuranosylimidazole-5-olate) are reported.

PMID- 16438063
TI  - "Fast-track"-rehabilitation in surgery, a multimodal concept.
AB  - The rates of postoperative local surgical complications (e.g. wound-infection,
      abscess, anastomotic leakage) and the postoperative mortality have markedly
      decreased over the past decades. However the occurrence of general medical
      complications (e.g. cardio-pulmonary or renal dysfunction, nosocomial infections,
      thromboembolism) after abdominal surgery is still frequent with an incidence of
      20-60% (1-6). "Fast-track"-surgery, also called "Fast-track"-rehabilitation or
      "ERAS" (enhanced recovery after surgery) programme, is a combination of different
      pre- and intraoperative measures, which have been mainly validated in elective
      colonic surgery, but they can be principally employed in all surgical settings.
      With this approach it is possible to accelerate the postoperative convalescence
      and reduce the rate of general complications markedly (4, 7-10).

PMID- 16438064
TI  - Management of high blood pressure in peripheral arterial disease.
AB  - Arterial hypertension (HTA) is a promoter of peripheral arterial disease (PAD) in
      association with other atherosclerotic risk factors. Systolic HTA is the most
      frequently noted form in such disease, secondary to marked increase in large
      artery stiffness. The existence of PAD confers on the hypertensive patient a very
      high cardiovascular (CV) risk, requiring an intensive global therapeutical
      approach. Treating HTA is one of such beneficial actions. The optimal blood
      pressure (BP) to be reached is at least < 140/90 mmHg but lower BP should be
      targeted if possible (< or = 130/80 mmHg). First of all, a modification of the
      lifestyle and diet should be proposed. But to reach such a low target, different
      antihypertensive agents must be very often used in association. The inhibitors of
      the renin-angiotensin system constitute one of the main axis of such drug
      treatment, after having avoided the pitfall of renal artery stenosis.

PMID- 16438065
TI  - Role of inflammation and infection in vascular disease.
AB  - Relationship of infection, inflammation, and atherosclerosis has been a subject
      of intensive investigation in recent years. Potential mechanisms whereby chronic
      infections may play a role in atherogenesis are myriad. Chlamydia pneumoniae (Cp)
      infection in early life may accelerate atherosclerosis, leading to cardiovascular
      complications. Other infections, simultaneously occurring with Cp, may result in
      a synergistic effect to promote atherosclerosis. Chronic Helicobacter pylori
      infection is known to increase the pH level of the gastric juice and to decrease
      ascorbic acid levels, both of which will lead to a reduced folate absorption. Low
      folate hampers the methionine synthase reaction. This leads to an increased
      concentration of homocysteine in the blood, resulting in damage of endothelial
      cells. Cytomegalovirus (CMV) infection is associated with accelerated
      atherosclerosis following cardiac transplantation; several studies have found
      that patients with a previous CMV infection had a high independent risk of
      restenosis after coronary angiography. Inflammatory markers are independent
      predictors of cardiovascular and cerebrovascular events. Large population-based
      studies such as the study from the MONICA (MONItoring trends and determinants in
      Cardiovascular disease) Augsberg Center in Germany, the Atherosclerosis Risk in
      Communities Study, the Women's Health Study, the Honolulu Heart Study, have also
      suggested the relation between the levels of CRP and risk of coronary disease.
      Over the past decade also another marker of inflammation has been studied;
      fibrinogen has been identified as an independent risk factor for CAD in several
      large prospective studies. All these studies suggested a new, possible role of
      markers of infection and inflammation beyond traditional cardiovascular risk
      factors, in the development and progression of atherosclerosis. However, the
      clinical and therapeutic implications of these results remain to be evaluated.
      Although antibiotic treatment of infections in CAD patients had no impact on
      mortality in large prospective trials, promising data is coming from smaller
      studies and further studies are needed to investigate the possibility to submit
      this category of high-risk patients to therapeutical approaches of primary
      prevention.

PMID- 16438066
TI  - The management of mycotic aortic aneurysms: is there a role for endoluminal
      treatment?
AB  - BACKGROUND: Mycotic aneurysms are rare. Conventional surgical options include
      ligation or excision with in-situ or extra-anatomical reconstruction. The use of
      endoluminal stenting for mycotic aneurysms in the presence of sepsis is
      controversial, but may be a temporising measure, or sometimes the only option in
      the management of critically ill patients who are not fit for surgery. METHODS: A
      literature review was undertaken using Medline, all relevant papers on
      endoluminal management of mycotic aneurysm were taken into account. RESULTS: Open
      surgical repair of mycotic aortic aneurysm is associated with considerable peri-
      and post-operative morbidity and mortality. Endoluminal treatment with stent
      grafts has been introduced as an alternative, and early results are promising.
      CONCLUSION: No level I evidence for the endoluminal treatment of mycotic
      aneurysms exists. Ideally a randomised controlled trial of open surgery versus
      endoluminal treatment should be performed but this may be difficult to perform
      because of the low incidence of infected aneurysms.

PMID- 16438068
TI  - Multi-detector row computed tomography angiography: an alternative imaging method
      for surgical strategy in lower extremity arterial occlusive disease.
AB  - In order to show the value of CT angiography in the pretherapeutic assessment of
      lower leg ischemia, we studied 93 CT angiographies in 85 patients. Two groups
      were defined according to the level of revascularization: 52 angioscanner were
      made prior to suprainguinal revascularization and 41 prior to infrainguinal
      reconstruction. Two decision attitudes were chosen by two different physicians, a
      radiologist and vascular surgeon, members of the same team. The attitudes where
      then compared in order to evaluate the value of CT angiography. The first
      attitude was a pragmatic strategy based on the images as interpreted by the first
      physician and on the intraoperative information including surgical treatment and,
      if necessary, angiography. This indicates that the results of this attitude cover
      the performed revascularizations. The second attitude determined a virtual
      strategy and was chosen by the second physician a posteriori, based solely on the
      medical file with the same CT angiography images. These two strategies were
      compared in order to assess the agreement on the level of the lesion and the
      choice of revascularization. In 84 CT angiographies (90.3%), the analysis of the
      lesions and the choice of lesions to be treated were identical. In 9.6% of scans
      the strategies were not comparable because the lesions were interpreted
      differently or the scans were difficult to read. The sensitivity of CT
      angiography in detecting lesions and guiding the therapeutic strategy was 96% and
      its positive predictive value was 93%. Follow-up was reported according to the
      life-table method to assess the overall outcome and the results in both groups.
      The overall survival rate at 12 months for 85 patients was 90%. Secondary patency
      rates at 12 months in the group of patients who underwent a suprainguinal and
      infrainguinal revascularization were 98% and 71% respectively. Overall limb
      salvage at 12 months was 94%. In this setting, CT angiography allowed us to
      select adequate treatment in the majority of cases. These results obtained after
      a strategy based on CT angiography images are comparable with the results as
      published in the literature after the strategy based on conventional angiography.

PMID- 16438067
TI  - Surgical management of acute perforation of peptic ulcers. A single centre
      experience.
AB  - INTRODUCTION: Acute perforation may occur in gastric and duodenal ulcers. During
      the past decade, the need for elective operation for peptic ulceration has
      decreased as medical treatment has improved. However, emergency operations for
      acute complications such as perforation or bleeding remain constant. Actually,
      the treatment of choice is simple suture-closure, with or without omentoplasty,
      and peritoneal lavage or even omentoplasty alone, associated with a high
      intravenous dose of inhibitors of the proton pump and Helicobacter pylori
      eradication, if needed. PATIENTS AND METHOD: The standard treatment in our team
      is to perform a peritoneal lavage and drainage and a simple closure of the ulcer
      with an omentoplasty. A first retrospective analysis was made on data collected
      from 1996 to 2001 and we completed a prospective study from 2001 to 2003 to
      compare our results with our old data and with data collected from other teams.
      RESULTS: The mean age and the mean ASA score were similar in the two groups. For
      the majority of the patients, the diagnosis was made from symptoms and the
      presence of free abdominal air. The delay between arrival in the emergency room
      and the operating room was significantly shorter in the second group, but
      operating time was longer in this group. Morbidity was more frequent in the first
      group but mortality remained quite similar. Our results indicate that in a
      trained team the morbidity has decreased as the delay in surgery decreased and
      that the rate of diagnosis on plain abdominal film has increased. Laparoscopic
      suture of a perforated peptic ulcer is as safe as the open procedure but allows
      the surgeon to search for another cause of free air and offers the possibility,
      if conversion is needed, to perform a shorter laparotomy.

PMID- 16438069
TI  - Hybrid treatment for thoracic and thoracoabdominal aortic aneurysms in patients
      unfit for open conventional repair.
AB  - PURPOSE: To describe a technique combining endovascular and conventional surgery
      for the treatment of distal aortic arch and thoracoabdominal aortic aneurysms.
      MATERIAL AND METHODS: In the last two years, we used hybrid approach to treat six
      patients with distal aortic arch or thoracoabdominal aortic aneurysms unfit for
      open conventional repair owing poor cardio-respiratory function. RESULTS: The
      primary technical success rate was 100%. Intraoperative mortality rate was 0;
      conversion to open conventional repair was never required. Mean operation time
      and blood loss averaged 256 minutes and 1233 ml, respectively. Neurological
      complications were not observed. Overall, two patients died postoperatively.
      During a mean 17-month follow-up, two minor type II endoleak occurred and were
      successfully managed with coil embolization. All stent-grafts and conventional
      bypasses were patent, and no stent-graft-related complication was observed.
      CONCLUSION: Our initial experience attests the feasibility and potential
      attractive alternative of hybrid treatment for distal arch and thoracoabdominal
      aortic aneurysms.

PMID- 16438070
TI  - Potential benefits of laparoscopic aorto-bifemoral bypass surgery.
AB  - BACKGROUND: This series aims to prove the positive impact of laparoscopic
      approach in aortofemoral bypass grafting. METHODS: It concerns a retrospective
      non randomized study comparing 58 consecutive patients treated with laparoscopic
      procedure (n = 30) and with a standard open procedure (n = 28) in a single
      center. The different operating times, the complications and the follow-up of
      these two groups are compared RESULTS: The demographics and angiographic data of
      the two groups were comparable. Operating time was longer in the laparoscopic
      group. However, we noticed a significant shorter hospitalisation stay (p <
      0.0001) after the laparoscopic procedure with a mean 5.1 days. There was no
      significant difference of morbidity. CONCLUSION: We suggest that the trans
      peritoneal approach is the best way in laparoscopic procedure in term of exposure
      and ergonomics. Laparoscopic aortofemoral bypass grafting is feasible, safe and
      effective. Shortening of operating time is observed as surgeon's experience
      grows.

PMID- 16438071
TI  - Aorto-caval fistulas: a review of eighteen years experience.
AB  - The operative treatment of 26 aorto-caval fistulas during the last 18 years is
      reviewed (24 male and two female patients; average of 65.3 year). Out of 1698
      cases presenting an abdominal aortic aneurysm, 406 presented with rupture, and 26
      had aorto caval fistula. In 24 cases (92.3%) it concerned an atherosclerotic
      aneurysm. One aneurysm with aorto-caval fistula was secondary to abdominal blunt
      trauma (3.8%), and one due to iatrogenic injury (3.8%). The time interval between
      first clinical signs of aorto-caval fistula and diagnosis, ranged from 6 hours to
      2 years (average 57,3 days). Clinical presentation included congestive heart
      failure infive patients (11.5%), extreme leg edema in 13 (50.0%), hematuria in 2
      (7.0%), renal insufficiency 2 (7.0%), and scrotal edema in six patients.
      Diagnosis was made by means of color duplex scan in eight patients (30.7%), CT in
      seven patients (27%), NMR in three patients (11.5%), and angiography in seven
      patients (27%). Most reliable physical sign was an abdominal bruit,present in 20
      patients (77%). In ten patients (38.4%) correct diagnosis was not made prior to
      surgery. The operative treatment consisted of transaortic suture of the vena cava
      (25 pts-96.0%), and aneurysm repair. Five operative deaths occurred (19,2%), and
      for all of them it concerned a misdiagnosis. Cause of death was myocardial
      infarction (one patient-3.8%), massive bleeding (one patient-3.8%), MOF (two
      patients-7, 0%), and colon gangrene (one patient-3.8%). Follow-up period varied
      from six months to 18 years (mean 4 years and two months). Long term results
      showed a 96% patency rate. No postoperative lower extremity venous insufficiency
      nor pelvic venous hypertension was observed post-operatively.

PMID- 16438072
TI  - Initial staging of malignant melanoma by positron emission tomography and
      sentinel node biopsy.
AB  - By a retrospective study and literature review we aimed to evaluate the accuracy
      of Sentinel Node Biopsy (SNB) and F-18-fluorodeoxyglucose positron emission
      tomography (PET) for early detection of lymph node metastases. MATERIAL AND
      METHODS: Every patient presenting with a malignant melanoma without clinical
      lymph node involvement and a Breslow index over 1 mm or a recurrence was
      subjected to a preoperative PET scan and a sentinel node biopsy. Over a period of
      10 months, 5 patients were included. They were submitted to conventional staging
      techniques, PET and SNB. RESULTS: In none of the patients the PET scan showed
      signs of lymph node involvement or distant metastases. However, two patients,
      both with a Breslow index of 1.4, had micrometastases in the sentinel node.
      CONCLUSION: Already in this small group of patients, PET scanning missed two
      metastases (40%). This is confirmed by several recent publications, stating that
      the resolution of positron emission tomography is about 5 mm and thus
      insufficient to detect micrometastases. Several larger series showed a
      sensitivity of PET to detect lymph node involvement of 15-50%. Therefore we
      conclude that PET is of limited use in these patients without palpable lymph
      nodes. Sentinel node biopsy however proves to be a useful tool and should be
      considered in the initial staging of malignant melanoma without palpable lymph
      node or distant metastases.

PMID- 16438073
TI  - Outcome of two salvage procedures for posttraumatic osteoarthritis of the wrist:
      arthrodesis or proximal row carpectomy.
AB  - PURPOSE: to compare a motion preserving procedure of the wrist with the wrist
      arthrodesis, the so-called gold standard in patients with posttraumatic
      wristpain. DESIGN: non randomized retrospective SETTING: University Hospital-
      referral centre PATIENTS: we studied two groups of patients with posttraumatic
      wrist pain due to osteoarthritis of the radiocarpal joint: one group of 35
      patients underwent a radiocarpometacarpal arthrodesis, the other group of 26
      patients a proximal row carpectomy (PRC). There were no significant differences
      in age and gender or hand dominance distribution. INTERVENTION: proximal row
      carpectomy versus radiocarpal arthrodesis. OUTCOME MEASUREMENTS: DASH (disability
      of arm, shoulder and hand) gripping force, return to activity, complications and
      reintervention frequence. RESULTS: Disability (DASH score) and regaining
      professional activity was significantly better in the PRC group. There was no
      significant difference in gripping force between the PRC and the arthrodesis
      group. Complications were less numerous. CONCLUSION: A mobility saving procedure
      as a PRC is preferable over an arthrodesis in patients with posttraumatic wrist
      osteoarthritis.

PMID- 16438074
TI  - The relationship between time of admittance and complications in paediatric
      tracheobronchial foreign body aspiration.
AB  - PURPOSE: Majority of tracheobronchial foreign body aspirations occur in
      paediatric age group and may constitute a life hazard. We examined the
      relationship between the time of admittance and complications in children with
      tracheobronchial foreign body aspiration. MATERIAL AND METHODS: Sex, age, time of
      admittance, presenting symptoms, radiological findings, and the nature of the
      foreign body were reviewed retrospectively in patients aged 16 and under follow
      up for tracheobronchial foreign body aspiration between January 1990 and January
      2005. Cases were randomly assigned into 6 groups based on admittance times.
      RESULTS: Within 15-year period, 263 children under the age of 16 were followed-up
      for tracheobronchial aspiration of foreign body. The most commonly aspirated
      foreign bodies included sunflower seed, peanut, hazelnut, walnut. While the
      pathology could be detected radiographically in 80.3% (n : 211) of the cases, in
      19.7% (n : 52) radiology was normal. All cases had rigid bronchoscopy under
      general anaesthesia. In 220 cases foreign body was detected and could
      successfully be removed in 209 cases. The remaining 11 cases required bronchotomy
      or pneumotomy to remove the foreign body. Among 679 cases operated for
      bronchiectasis during the same period, 22 cases (3.2%) had foreign body as the
      aetiology. No complications were observed when the patients presented to the
      hospital within the first 24 hours after the aspiration while fever, purulent
      sputum, haemoptysis and bronchiectasis were noted in those presented later. Most
      of the complications were medically treated. CONCLUSION: Paying medical attention
      within the first 24 hours after the aspiration of foreign bodies is critical in
      order to accomplish a complication-free course. Organic foreign bodies and
      retention period of 30 days and over, constitute major risk factors in the
      development of bronchiectasis. It is advisable to perform bronchoscopy in the
      early stages of all suspected cases to avoid serious complications such as
      bronchiectasis.

PMID- 16438075
TI  - Do we need to use subcutaneous suture for pilonidal sinus treated with excision
      and simple primary closure?
AB  - OBJECTIVE: Pilonidal sinus (PS) is a chronic intermittent disease. There are
      numerous surgical treatment procedures that have been previously reported, yet
      none have been proved to be ideal. The main issues concerning the surgical
      treatment of PS are simplicity and cost-effectiveness. This study is designed to
      research the possibility of decreasing operation costs in the excision and simple
      primary closure technique of PS by omitting subcutaneous suture usage. MATERIALS
      AND METHODS: 152 male patients with chronic PS were included in the study. All
      patients were treated with excision and simple primary closure technique and
      randomized into two groups. Group-I (n = 74) received subcutaneous closure with
      2/0 polyglactin sutures, but Group-II (n = 78) did not. Wound edges were re
      approximated by using deep interrupted matress 0 no polypropylene sutures in both
      groups. RESULTS: In Group-I; overall 7 (9.5%) early complications were noted;
      2(2.7%) wounds broke down and 5 (6.7%) experienced superficial wound infections.
      Any late wound complications were noted. A total of 98 polypropylene and 104
      polyglactin sutures were used. In Group-II; overall 5 (6.4%) early wound
      complications were noted; 3 (3.8%) had wound dehiscence and 2 (2.6%) developed
      superficial wound infections. Also, 1 (1.3%) late wound complication (wound
      dehiscence) occurred. Overall 104 polypropylene sutures were used. CONCLUSION:
      Excision and simple primary closure is a simple and cost effective surgical
      procedure in the treatment of PS. Omitting the use of subcutaneous sutures makes
      the procedure simpler and decreases the operation costs.

PMID- 16438077
TI  - Expression of bcl-2 in papillary thyroid cancers and its prognostic value.
AB  - PURPOSE: Papillary thyroid cancer has a good prognosis. This favourable prognosis
      may be attributed to the apoptotic tendency of the cancer cells. This study aims
      to evaluate the expression of bcl-2, which is an antidote of apoptosis, and aims
      to evaluate the value of bcl-2 as a prognostic marker in papillary thyroid
      cancer. MATERIAL-METHODS: Bcl-2 expression in the archival materials of 31
      patients with papillary thyroid cancer was examined with immunohistochemical
      methods using bcl-2 and p-53 stains. The results were compared with 31 normal
      thyroid tissue specimens, which consisted of the contralateral lobes of these
      patients. The results were then analyzed in accordance with the clinical features
      of the patients. RESULTS: Thirty (96.7%) patients of the control group were
      positive for bcl-2 whilst one (3.3%) was negative. The staining for bcl-2 was
      positive in 12 (%75) patients with microcarcinomas (p < 0.05) and 13 (86.6%) with
      papillary cancers (p > 0.05). Two cases of the papillary cancer group were
      admitted to the hospital with local recurrence (6.4%) and both were positive for
      bcl-2 (p > 0.05). All cases (4/31), whose MACIS scores were higher than 7 were
      positive for bcl-2. Twenty-one of 27 cases whose MACIS scores were lower than 7
      (77.7%) were positive for bcl-2 (p > 0.05). All tumours of this series were
      negative for p-53 immunstaining. CONCLUSION: The rate of bcl-2 expression in
      microcarcinomas of papillary thyroid cancer decreases when compared to normal
      thyroid tissue. This may be an early sign of oncogenesis, and a reason for the
      favourable prognosis in microcarcinomas. However, bcl-2 cannot be used as a
      prognostic marker.

PMID- 16438076
TI  - Emergency surgery for massive haemoptysis.
AB  - BACKGROUND: Massive haemoptysis (600 ml in 24 hours) results in considerable
      mortality and deserves appropriate management. Since it is life threatening, lung
      resection remains the surgical treatment of choice in unrelenting haemoptysis.
      MATERIAL AND METHODS: We retrospectively reviewed all patients (n = 29) who were
      referred to our clinic between January 1994 to September 2001 with massive
      haemoptysis (> 600 ml/24 h). All patients had uncontrollable haemorrhage and/or
      failure of conservative treatment. After initial resuscitation, assuring adequate
      airway and providing adequate intravenous access, emergency thoracotomy was
      performed in all patients following rigid bronchoscopy (n = 27) in order to
      localize the bleeding. RESULTS: The most common underlying cause of the massive
      haemoptysis was pulmonary tuberculosis (n = 10) followed by emphysema in 4, lung
      cancer in 3, collagenous vascular disease in 2 and aspergilloma in one patient.
      Seventeen lobectomies (58.6%), 5 pneumonectomies (17.2%), 3 segmentectomies and 3
      bilobectomies were done whereas physiological lung exclusion was performed in one
      patient. Haemoptysis could be controlled in all patients. Rate of operative
      morbidity and hospital mortality were 27.5% and 11.5% respectively. We recorded
      one patient with recurrent haemoptysis who was treated by completion
      pneumonectomy. CONCLUSION: Despite the debate over definition of massive
      haemoptysis and indication for surgery in these patients, emergency pulmonary
      resection provides an effective treatment with acceptable morbidity and mortality
      in patients with massive haemoptysis.

PMID- 16438078
TI  - Is synchronous bowel anastomosis safe?
AB  - In this study, we investigated the effects of synchronous anastomosis on
      intestinal healing in experimental colonic resection. Sprague-Dawley rats were
      randomized into 3 groups; control (group I), single anastomosis (group II) and
      synchronous (double) anastomosis (group III). Single and proximal anastomoses
      were located 3 cm distal to caecum, and distal anastomoses were done 3 cm distal
      to them. On the 7th postoperative day, bursting pressure, hydroxyproline level
      and histology of the anastomotic site were assessed. Bursting pressures and
      hydroxyproline levels indicated that impaired healing of proximal anastomoses in
      group III was evident. Proximal anastomoses in group III had the lowest
      hydroxyproline value and bursting pressure level. Significant fibrosis was
      observed in the histological examination of distal anastomoses in group III.
      Double colonic anastomoses is not as safe as single anastomoses and involves
      additional risk. The healing of proximal anastomosis is significantly altered
      after experimental synchronous resection.

PMID- 16438079
TI  - Transmesosigmoid hernia: report of a case and review of the literature.
AB  - We report a case of a transmesosigmoid hernia in a 6 weeks postpartum woman. We
      found 14 previous reports of this rare type of internal hernia. Our patient
      presented with acute abdominal pain and developed a small intestinal obstruction.
      History, clinical and radiographic examination were not diagnostic. An early
      laparoscopy was performed and a herniation of a small intestine loop through a
      hole in the sigmoid mesocolon was seen. The hernia was reduced and the defect in
      the sigmoid mesocolon was closed laparoscopically. The small intestine was viable
      and enterectomy could be avoided. The role of laparoscopy and potential causes of
      this type of hernia are discussed.

PMID- 16438080
TI  - Axillary giant lipoma: a case report.
AB  - Lipoma are the most frequent mesenchymal soft tissue tumours but rarely present
      huge sizes in their cutaneous localization. Some cases of so-called "giant
      lipomas" have been reported in the literature and here is presented a giant
      lipoma of the axillary area which is, to our best knowledge, the second report of
      such a giant lipoma in this localization.

PMID- 16438081
TI  - Breast hamartoma: a case report.
AB  - Breast hamartoma is a benign and rare tumour consisting of glandular fat and
      fibrous tissue. A 36-year old woman was admitted to our clinic, complaining of a
      mass in her right breast since two months. Ultrasonographic and mammographic
      examinations revealed a 10 cm mass diagnosed as fibroadenolipoma. Total excision
      of the mass was performed without any complication. Histopathological examination
      revealed fibroadenomatous hamartoma.

PMID- 16438082
TI  - Development of early malignant bilateral breast disease in relation to
      antidepressant treatment.
AB  - The aim of this study is to present two rare cases of young female patients who
      were under antidepressant medication and developed bilateral breast disease;
      histology confirmed the noninvasive, malignant nature. The role of that type of
      agents in the breast pathology is briefly discussed, based on the data of the
      current literature.

PMID- 16438083
TI  - Laparoscopy in the management of impalpable testicle.
AB  - PURPOSE: In paediatric urology, one of the main applications of laparoscopy is
      the evaluation and treatment of impalpable testis. Herein we present our initial
      experience with laparoscopy in patients with impalpable testis. MATERIAL AND
      METHODS: Laparoscopy was performed under general anaesthesia on 13 patients. If
      the internal spermatic vessels and vas deferens made their way into the internal
      inguinal ring, the inguinal canal was dissected. Laparoscopic orchiopexy or
      orchiectomy was performed in cases with intra-abdominal testis. If the internal
      spermatic vessels found terminated intraperitoneally with a blind-end, the case
      was considered as a vanishing testis. RESULTS: Thirteen boys, aged from 18 months
      to 25 years (median 9.8 years) were identified with 21 impalpable testes. 14 of
      the 21 impalpable testes, the vas and the vessels were through the internal ring,
      and the inguinal region needed dissection. Orchiopexy was performed on 12 testes
      and orchiectomy was performed on two atrophic testes. Four of 21 testes were
      intra-abdominally localized. Laparoscopic orchiopexy was performed in two testes
      and laparoscopic orchiectomy was performed in two testes. Two boys were diagnosed
      as vanishing testes; the absence was unilateral on the left side in one case and
      bilateral in the other. CONCLUSION: Diagnostic laparoscopy is a very helpful,
      minimally invasive technique in the diagnosis of impalpable testes especially
      when ultrasonography and/or computed tomography are not informative enough. In
      addition, orchiectomy and orchiopexy can be done as laparoscopically in the
      patients with intra-abdominal testes. Therefore, the laparoscopy has an important
      role in the diagnosis and treatment of impalpable testes.

PMID- 16438084
TI  - Pancreas pseudocyst associated with L-asparaginase treatment: a case report.
AB  - A major complication of L-asparaginase used in the treatment of paediatric
      malignancies in children is pancreatitis (2%-16%). However, only seven paediatric
      cases of pancreatic pseudocyst caused by the utilization of the agent have been
      reported in literature. We present the case of a 5-year old girl who had
      abdominal pain and epigastric dullness after the third course of BMF-95 protocol
      with a diagnosis of ALL. A pancreatic pseudocyst of 10 x 10 cm size was found by
      abdominal tomography. The cyst was treated by percutaneous external drainage,
      total parenteral nutrition (TPN), administration of octreotide and antibiotherapy
      for one month. Percutaneous external drainage has proven to be an effective,
      noninvasive method in this special case with a systemic disorder and the high
      risk of mortality should a surgical intervention have been performed.

PMID- 16438085
TI  - Diffuse intestinal diverticulosis: a case report.
AB  - We report an asymptomatic case of diffuse intestinal diverticulosis
      simultaneously affecting duodenum, jejunum and colon. The patient presented signs
      of progressive systemic sclerosis, which supports the hypothesis in the
      literature of an aetiological link.

PMID- 16438086
TI  - An adult adrenal neuroblastoma: a case report.
AB  - Neuroblastoma of the adrenal gland is an extremely rare tumour in adulthood
      although it is one of the most common malignancies in childhood. In this report,
      we present a 52-year-old man who had a left adrenal mass on preoperative imaging.
      On laboratory, slightly elevated catecholamine metabolites were detected in the
      urine that was collected over 24 hours. He was operated and the mass was resected
      in en-block manner along with the regional lymph nodes. The histopathological
      examination of the specimen revealed the diagnosis of neuroblastoma. He had no
      metastatic disease at the time of diagnosis and received chemotherapy after the
      operation. However, the prognosis was poor and he died 10 months after the
      operation. Although neuroblastoma of adrenal gland is rare in adulthood, it
      should be considered in the differential diagnosis for patients with adrenal
      masses.

PMID- 16438087
TI  - A simple antireflux barrier for cologastric anastomosis in colonic interposition.
AB  - Colon interposition has been successfully employed as a oesophageal replacement
      procedure in paediatric patients. One of the complications of the procedure is
      gastrocolic reflux. A simple antireflux procedure is reported in this work.

PMID- 16438088
TI  - Hola trial: ventral hernia open versus laparoscopic repair. A call for
      participants.

PMID- 16438089
TI  - Let's talk about challenges surrounding addiction in cancer pain.

PMID- 16438090
TI  - 2006 brings new cancer care reimbursement changes to both hospital and office
      based settings.

PMID- 16438091
TI  - Avian flu--are you prepared to fight a pandemic?

PMID- 16438092
TI  - Occupational health nursing 2004 practice analysis report.
AB  - As a certifying body for occupational health nurses in the United States and
      Canada, the American Board for Occupational Health Nurses, Inc. (ABOHN) must
      ensure its certification examinations validly reflect current occupational health
      nurse practice. This report presents information from the ABOHN 2004 practice
      analysis. The study's primary purpose was to analyze areas of knowledge, skill,
      and ability for occupational health nurses as reflected by the tasks they perform
      to guide refinement of ABOHN's certification examinations. A valid and reliable
      survey instrument, containing demographic and job-related questions and 172 task
      statements was developed. A total of 5,586 surveys (4,921 Web-based and 665
      paper) were made available to occupational health nurses throughout the United
      States and Canada. The usable response rate was 23.5% (N = 1,223). Decision rules
      were used to determine which survey tasks were appropriate for inclusion in
      Certified Occupational Health Nurse (COHN) and Certified Occupational Health
      Nurse Specialist (COHN-S) certification examination blueprints. The revised
      blueprints were used to develop new examinations. Study data also validated the
      existing ABOHN Case Management (CM) specialty examination blueprint, and verified
      occupational health nurse roles and responsibilities related to safety programs.
      Based on analysis of the safety-related items, ABOHN in collaboration with the
      Board of Certified Safety Professionals, has created a safety management
      credential (SM) and associated examination that certified occupational health
      nurses may use to verify their safety role proficiency.

PMID- 16438093
TI  - Factors associated with work-related injury among hospital employees: a case
      control study.
AB  - The Central Arkansas Veterans Healthcare System (CAVHS) spends $1 million
      annually on occupational illnesses and injuries. To address the problem of
      injuries among hospital employees, a retrospective case-control study was
      conducted to examine select risk factors for work-related injuries (WRI) among
      CAVHS employees. Study methods included a review of employee health charts and
      computer and manual databases from 1997 to 2002 (N = 2,050). The researchers
      found that WRI increased with age; WRI occurred more often in women than in men;
      WRI was greater among maintenance and custodial staff compared to direct
      caregivers, and less among clerical staff; WRI occurred less often in part-time
      than full-time staff; and WRI increased with increasing body mass index.
      Developing standards, guidelines, and policies for preplacement screening,
      preventive measures, training, and education may help to minimize WRI and
      associated costs.

PMID- 16438094
TI  - Musculoskeletal injuries among ultrasound sonographers in rural Manitoba: a study
      of workplace ergonomics.
AB  - The purpose of this study was to compare the epidemiology of musculoskeletal
      injuries and workplace ergonomics among rural-based sonographers compared to
      urban-based sonographers. The authors also tested the use of a biomechanical
      software program to assess load on the spine and upper extremity joints. A mail
      in survey was sent to all practicing sonographers in rural Manitoba, and on-site
      video-taped ergonomic and biomechanical evaluations were completed for four
      sites. Rural-based sonographers appear to have greater work stress related to
      waiting lists, use of outdated and non-adjustable equipment, and high client
      load. They also do not advocate for better working conditions because they are
      few in number and geographically distant from one another. Use of the
      biomechanical software proved minimally useful. Information related to industry
      standards and greater collaboration is needed to promote workplace health for
      sonographers.

PMID- 16438095
TI  - Legislation affecting occupational health nursing: identifying relevant laws and
      regulations.
AB  - Occupational health nurses are challenged by the complexity of the laws and
      regulations governing their practice. Establishing a practice-based regulatory
      framework and applying an efficient review process simplifies that challenge. For
      those interested in expanding this framework beyond laws and regulations, a
      number of agencies and organizations that establish standards and recommendations
      relevant to the occupational health setting exist, such as the Centers for
      Disease Control and Prevention (www.cdc.gov), the National Institute for
      Occupational Safety and Health (www.cdc.gov/niosh), and the American Conference
      of Governmental Industrial Hygienists (www.acgih.org). Materials published by
      these agencies (e.g., the CDC "Adult Immunization Schedule;" NIOSH
      "Recommendations for Protecting Outdoor Workers from West Nile;" American
      Conference of Governmental Industrial Hygienists "Guide to Occupational Exposure
      Values," "TLVs," and "BEIs") are often of value to occupational health nurses and
      worth their attention.

PMID- 16438096
TI  - The new food pyramid.

PMID- 16438097
TI  - Attainment of goals from national guidelines among persons with type 2 diabetes:
      a cohort study in an academic family medicine setting.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients
      with diabetes, but goals for reduction of modifable cardiovascular risk factors
      are difficult to achieve in primary care. We evaluated the change in risk factor
      control for a cohort of patients with diabetes and hyperlipidemia over a four
      year period, as well as the change in proportion of patients meeting clinical
      practice guideline goals. METHODS: Medical records were reviewed from a cohort of
      86 randomly selected persons with type 2 diabetes in an academic family medicine
      setting. Data were abstracted to assess the attainment of and change in five
      treatment goals related to glycemic, blood pressure, and lipid control from 1999
      2003. Descriptive statistics were applied to demographic variables. Mean
      differences in outcomes were assessed with the paired t-test. The McNemar test
      was used to assess non-parametric variables, and the Wilcoxon signed ranks test
      was applied to differences achieved in mean goal scores for outcome variables.
      RESULT: The mean numbers of treatment goals attained were 2.76 (SD = 0.92) in
      1999 and 2.48 (SD = 1.1) in 2003. Significant improvements were noted in the mean
      values of HbA1c (0.4% decrease, p = 0.03), diastolic blood pressure (4.3mmHg
      decrease, p < 0.001), low-density lipoprotein cholesterol (LDL-C; 10.6 mg/dL
      decrease, p < 0.01), and high-density lipoprotein cholesterol (HDL-C; 8.3 mg/dL
      increase, p < 0.001) over the four-year study interval. No significant
      differences were noted in the percent at goal during the study for HDL-C or for
      HbA1c. A significant decrease was found in the percent at goal from 1999-2003 for
      LDL-C from 79% to 40%, respectively). The decrease in the percent LDL-C at goal
      was explained by the more stringent practice guideline goals introduced in 2001
      for diabetes (i.e., LDL-C < 100 mg/dL). CONCLUSION: Despite significant
      improvement in mean values of modifiable risk factors, the percent of patients
      meeting 2003 guideline goals for HbA1c, systolic blood pressure, and LDL
      cholesterol did not improve. These findings suggest that patient-level
      improvements may not be adequate indicators of a practices achievement of
      guideline recommendations. Percent attainment of guideline goals may be a useful
      peformance measure of practice-level quality improvement initiatives.

PMID- 16438098
TI  - Trends in up-to-date status in colorectal cancer screening, North Carolina, 1998
      2002.
AB  - BACKGROUND: Rates of colorectal cancer (CRC) screening are rising nationwide. Our
      purpose was to determine the proportion of North Carolina adults who were up-to
      date with CRC screening in 1998-2002 and analyze trends by socio-demographic
      subgroups. METHODS: We examined data from the North Carolina Behavioral Risk
      Factor Surveillance System. For 1998, 1999, 2001, and 2002, we determined the
      proportion of respondents 50 years old and older who were up-to-date, defined as
      a home fecal occult blood test (FOBT) in the past 12 months and/or a
      sigmoidoscopy or colonoscopy in the past five years. We examined trends in up-to
      date status in all respondents and in selected socio-demographic subgroups. We
      also examined the characteristics of respondents who were up-to-date in 2001
      2002. RESULTS: From 1998-2002, the percentage of respondents 50 years old or
      older who were up-to-date with CRC screening increased from 46.1% to 54.0% (test
      for trend, p < 0.0001). The proportion who were up-to-date increased among those
      50-74 years old, those with a high school or college education, and those with
      incomes less than dollar 25,000. Proportions that were up-to-date did not
      significantly increase among African Americans and respondents with less than a
      high school education. In 2001-2002, we found low percentages that were up-to
      date among adults 50-54 years old Hispanics, and the uninsured CONCLUSIONS: The
      proportion of North Carolina adults who are up-to-date with CRC screening is
      increasing but not across all socio-demographic groups. These results indicate
      that there are subgroups that need to be reached with screening programs. Efforts
      to educate the public and providers about CRC screening should continue.

PMID- 16438099
TI  - Assuring the accessibility of basic dental care services: issues of workforce
      supply, organization of care, and education.

PMID- 16438100
TI  - Defining the need for dental care in North Carolina: contributions of public
      health surveillance of dental diseases and conditions.

PMID- 16438101
TI  - The dentist workforce in North Carolina 2005: a commentary.

PMID- 16438102
TI  - Access to dental care for young children in North Carolina: history and current
      status of workforce issues.
AB  - The 2000 North Carolina IOM report contained 23 recommendations. To date 16 have
      been fully or partially implemented. This represents progress, but accomplishing
      full compliance remains a goal. Absent new training programs in our state, as
      current federal training grants phase-out, identifying financial support to
      continue training an adequate number of pediatric dentists for North Carolina
      will be a challenge.

PMID- 16438103
TI  - Dentist participation in Medicaid: key to assuring access for North Carolina's
      most underserved.

PMID- 16438104
TI  - Special care dentistry delivers a formula for change: a model has been developed
      but must be implemented statewide.

PMID- 16438105
TI  - Public health dentistry and dental education services: meeting the needs of the
      underserved through community and school-based programs.

PMID- 16438106
TI  - The role of free dental programs in care provision for the underserved.
AB  - Due to the shortcomings of the existing healthcare delivery system in general,
      and the dental field in particular, safety net programs are not simply optional;
      they are mandatory to help meet the overwhelming healthcare needs of the
      underserved. Free dental clinics are a vital part of this system, and indeed,
      millions of actual dollars, millions of dollars worth of services and thousands
      of hours of professional manpower are donated each year to provide free dental
      services for the needy. The short-term benefits of these clinics are obvious, the
      rendering of dental care to tens of thousands of individuals per year who would
      otherwise go without. The long-term advantages may be somewhat less than obvious,
      however. Given that most dental professionals have limited contact with the
      underserved, the free clinics offer the opportunity to bring in volunteer
      dentists, hygienists, and dental assistants who may then gain first-hand
      knowledge of the access crisis and work directly with North Carolina's growing
      population in greatest need of dental care. Additionally, the free clinics often
      offer the same benefit for dental students from the University of North Carolina
      at Chapel Hill, as well as for undergraduate pre-dental students. This is a key
      aspect, as for every one of these students who may eventually enter the dental
      profession with a willingness to provide for the underserved population, tens of
      thousands of individuals in need could potentially receive dental treatment over
      the span of a dental career. The challenges of beginning and maintaining a free
      dental program over the long term are daunting. However, for those willing to
      invest the time and effort, the resources are available for long-term success
      with a resultant significant, positive impact on the dental care access crisis
      now in existence. As stated by Dr. Franklin M. Boyar in describing his free
      dental program in Florida, " PROJECT: Dentists Care is simply an organization
      that brings together unmet health needs of indigent populations within our
      communities with the desire of individual dentists to help their fellow man,
      along with the responsibility of a profession to deliver needed care to the
      underserved." Inherent in consideration of itself as a profession is the
      understanding by the component members of dentistry that it is indeed a
      responsibility, not simply an option, to deliver needed dental care to all
      citizens, regardless of their ability to pay. At the heart of any successful
      resolution of the dental care access crisis is the ability of dental providers to
      accept this responsibility, significantly increase Medicaid acceptance, willingly
      participate in access initiatives, and provide the care for which they have been
      granted licensure by the citizens of North Carolina.

PMID- 16438107
TI  - Improving access to dental care remains a priority of one of North Carolina's
      largest philanthropies.

PMID- 16438108
TI  - Access to primary dental care: a commentary on the economics of dental practice
      and thoughts on solutions to improve access to primary dental care.

PMID- 16438109
TI  - Improving oral health in North Carolina: exploring the potential of a new School
      of Dentistry at East Carolina University.

PMID- 16438110
TI  - Preventing child abuse and neglect.

PMID- 16438111
TI  - Effects of 5-HT1A receptor agonist and antagonist on anxiety in intact and
      ovariectomized female rats.
AB  - The purpose of this work was to study the role of 5-HT1A receptors on the level
      of anxiety in adult intact and ovariectomized (OVX) female rats. The influence of
      chronic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.)
      and 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg, i.p.) given for 14 days alone
      or in combination with 17beta-estradiol (0.5 microg i.m./rat/day) was studied on
      behavior in the elevated plus maze. In intact females administration of NAN-190
      resulted in significant increase in the number of enterings and the time spent on
      the open arms in every phase of the estrous cycle, however, 8-OH-DPAT failed to
      modify these parameters. In OVX females 8-OH-DPAT alone or in combination with
      17beta-estradiol significantly increased the number of enterings and time spent
      on the open arms. On the contrary, NAN-190 alone or in combination with 17beta
      estradiol in OVX females failed to evoke behavioral changes in the elevated plus
      maze. Thus, the 5-HT1A receptor antagonist NAN-190 induced anxiolytic effect in
      intact female rats, while 5-HT1A receptor agonist 8-OH-DPAT produced an
      anxiolytic profile on OVX rats. Results of this work specify the involvement of 5
      HT1A receptors in behavioral mechanisms of anxiety in OVX female rats.

PMID- 16438112
TI  - Involvement of 5-HT1A receptors in passive avoidance learning in intact and
      ovariectomized female rats.
AB  - The influence of chronic administration of 5-HT1A receptor agonist 8-OH-DPAT
      (0.05 mg/kg, s.c.) and 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg, i.p.)
      injected for 14 days alone or in combination with 17beta-estradiol (0.5 microg
      i.m./rat/day) was studied on passive avoidance performance (PAR) and on behavior
      in the open field test in adult intact and ovariectomized (OVX) female rats.
      Administration of 5-HT1A receptor antagonist NAN-190 alone significantly improved
      PAR (p<0.05) in intact females with proestrus and estrus and in OVX females.
      Administration of 5-HT1A receptor agonist 8-OH-DPAT alone or in combination with
      17beta-estradiol significantly (p<0.05) improved PAR in OVX rats and failed to
      normalize PAR in intact rats with proestrus and estrus. Results of the work
      specify the involvement of 5-HT1A receptors in the mechanisms of passive
      avoidance learning in OVX female rats.

PMID- 16438113
TI  - Melatonin restores diminished neurogenic reactivity of the juvenile rat tail
      artery.
AB  - The effect of melatonin on neurogenic reactivity of the juvenile rat tail artery
      segment was studied. The electrical field stimulation-evoked contraction of the
      segment decreased in the course of the experiment. Melatonin (0.1 microM) applied
      at different time points of the experiment produced an increase in the
      contraction, which directly correlated with a spontaneous decrease in the
      electrical field stimulation-evoked response. The increase in the potentiating
      effect of melatonin in the course of the experiment was not due to sensitization
      of the segment to this substance. Noradrenaline-evoked contraction of the vessel
      segment was not changed by melatonin. The data indicate that melatonin restores
      the diminished neurogenic reactivity of the juvenile rat tail artery probably by
      potentiation of the contractile response of the vessel, but this effect is hardly
      due to a change in sensitivity of the postjunctional membrane to noradrenaline.

PMID- 16438114
TI  - Effect of single neonatal or repeated benzpyrene exposure on the serotonin
      content of immune cells in young male rats.
AB  - In earlier experiments single benzpyrene treatment of newborn rats caused strong
      alterations in the endorphin content of adult rats' immune cells. In the present
      experiments young (4-6 weeks old) male rats were studied for demonstrating the
      effect of the single neonatal or repeated (neonatally and at weanling) benzpyrene
      exposure on the serotonin content of immune cells (blood lymphocytes, monocytes,
      granulocytes; peritoneal fluid lymphocytes, mast cells, monocytes and
      granulocytes, thymic lymphocytes). Flow cytometric analysis showed that 50 microg
      benzpyrene treatment of five-week-old animals was ineffective after 5 days and
      this was the situation four weeks after single neonatal (20 microg) benzpyrene
      exposure. However, the repeated treatment of neonatally benzpyrene exposed 4
      weeks old animals after 5 days resulted in elevated blood and thymic lymphocyte
      serotonin amount and in one index (peritoneal monocyte-granulocyte group) reduced
      serotonin content. This means that neonatal benzpyrene treatment does not
      influence directly the serotonin content (production or transport) of immune
      cells (unlike to the endorphin content) however, sensitizes them to a following
      benzpyrene exposure. The results widen the list of harmful effects (influencing
      steroid receptor binding, sexual behavior and immune cells' endorphin content) of
      perinatal benzpyrene exposure.

PMID- 16438115
TI  - Reduction of plasma lactate elevation and proteinuria by a complex dietary
      supplement in swimmers during over-loading training.
AB  - Endurance training aiming at eliciting further increase of physical performance
      of competitive athletes demands serious time and intensity constraints. In
      addition, very high intensity training could lead to "over-loading" frequently
      associated with increased concentration of plasma lactate after maximum intensity
      exercise and proteinuria. We hypothesized that a newly available complex dietary
      (CD) supplement by providing the necessary substances and cofactors for increased
      tissue metabolism would reduce the increase in plasma lactate concentration and
      proteinuria after maximum intensity exercise in swimmers undergoing high
      intensity training and exercise (70 km/week, for 6 weeks) period. Subjects
      involved in the investigation were junior swimmers (n = 10). Data were collected
      four times during the third macrocycle of training; 1st: before, 2nd: after 10
      days and 3rd: 14 days after withdrawal of CD-supplement, whereas 4th: after 10
      days of placebo treatment. The study was a double-blinded random controlled
      investigation. In the first period, plasma lactate concentration was 8.4 +/- 2.1
      mmol/l, whereas protein level in the urine was 8.9 +/- 5.8 mg/l. After use of CD
      supplement plasma lactate concentration significantly decreased to 5.5 +/- 1.9
      mmol/l and proteinuria decreased to 1.3 +/- 2.1 mg/l (p<0.05). Importantly, the
      intensity and the volume of the training did not change during the observation
      period. Thus, use of CD-supplement significantly reduced the increase in plasma
      lactate and proteinuria after maximum intensity exercise in athletes (swimmers)
      undergoing high endurance training despite maintained training load. We propose
      that the special components of CD-supplement support the mechanisms responsible
      for lactate elimination and reduction of protein catabolism and/or increase of
      protein reabsorption. These adaptations are likely to allow the athletes to
      undergo higher intensity training resulting in greater performance.

PMID- 16438116
TI  - Origin and mediation of secretion induced by oral phytohaemagglutinin (PHA) in
      rats.
AB  - After oral administration several gut-binding lectins induce accumulation of
      liquor and amylase in the proximal small intestine. Orally administered Phaseolus
      vulgaris phytohaemagglutinin (PHA) was used to study the mediation of these
      effects in rats. The regulation of amylase secretion clearly differed from that
      of the liquor. The amylase activity was of pancreatic origin, in agreement with
      the known cholecystokinin-releasing effect of PHA. It appears that CCK exerts its
      effect both directly and by facilitating neural stimulatory pathways. Intestinal
      secretion was identified as the source of the liquor, without a contribution by
      other secretions. It was mediated by a local cholinergic reflex with the
      involvement of both muscarinic and nicotinic acetylcholine receptors. It is
      speculated that the observed enteric reflex may enable the gut to transport
      secreted antibacterial peptides or secretory antibodies from the crypts to
      adherent bacteria on adjacent villi.

PMID- 16438117
TI  - Effect of selected alcohol dehydrogenase inhibitors on the human heart lactate
      dehydrogenase activity--an in vitro study.
AB  - Metabolic acidosis complicates methanol, ethylene glycol and other alcohol
      intoxications. It is caused firstly by acid metabolites and secondly by the
      lactate elevation. The aim of the study was to evaluate the effect of alcohol
      dehydrogenase (ADH; EC 1.1.1.1) inhibitors and substrates: 4-methylpyrazole (4
      MP), cimetidine, EDTA, ethanol and methanol on lactate dehydrogenase (LDH; EC
      1.1.1.27) activity. The activity of LDH was determined spectrophotometrically in
      in vitro human heart homogenates with the mentioned compounds at 0.01, 0.1, 1.0
      mM concentrations of 4-MP, cimetidine, EDTA, and 12.5, 25.0, 50.0 mM of ethanol
      and methanol. The LDH activity was significantly inhibited by 0.1 mM (p<0.05) and
      1.0 mM (p<0.01) 4-MP and 1.00 mM EDTA (p<0.05). Higher LDH activity vs. control
      was observed in the samples incubated with all studied ethanol and methanol
      concentrations but these differences were not statistically significant. Thus, 4
      MP was found to be the most effective inhibitor of LDH of all compounds tested.
      Therefore, such effect of 4-MP seems to be an additional advantage in methanol
      and ethylene glycol intoxications.

PMID- 16438118
TI  - The history of bronchial asthma from the ancient times till the Middle Ages.
AB  - The aim of the paper is to give an overview of the knowledge on asthma through
      the history of mankind. The text begins with ancient China and it is finished
      with the medicine of Middle Age. During this time, a lot of theories came and
      this appeared about the etiology and therapy of the disease. The paper is giving
      a short description of the changing medical views during this very long period
      including China, Egypt Greco-roman period, Mesopotamia, the Hebrews, the
      physicians of India, the pre-Columbian medicine in the America and the Arabic
      world, and partly the European medicine of the Middle Ages.

PMID- 16438119
TI  - Role of calcium-activated potassium channels in the regulation of basal and
      agonist-elevated tones in isolated conduit arteries. Short communication.
AB  - Functional role of calcium-activated potassium (KCa) channels on the basal and
      agonist-elevated arterial tones was investigated in isolated rabbit aorta,
      porcine and canine coronary arteries as well as in human internal mammary artery.
      The vascular tones enhanced by contractile agents were increased further by
      preincubation of these conduit blood vessels with selective (charybdotoxin or
      iberiotoxin) or nonselective (tetraethylammonium) inhibitors of KCa channels. The
      basal tone (without an agonist) was increased only in the canine coronary artery.
      The results indicate a feed-back regulatory role of KCa channels counteracting
      the vasospasm of conduit arteries.

PMID- 16438120
TI  - Resource-limited settings: a nurse's perspective.

PMID- 16438121
TI  - Enfuvirtide nursing guidelines: a report from the Association of Nurses in AIDS
      Care Expert Panel on Enfuvirtide.
AB  - Enfuvirtide is the first of a new class of antiretrovirals know as fusion
      inhibitors approved for the treatment of HIV infection. It is administered via a
      subcutaneous injection. The patient is responsible for reconstitution from a
      powder and self-injection. Nurses caring for patients using enfuvirtide need a
      solid knowledge base about enfuvirtide administration and side effects in order
      to effectively educate and manage patients taking enfuvirtide. Enfuvirtide's
      safety and efficacy reported from phase III trials are summarized. Nursing
      guidelines were developed by the Association of Nurses in AIDS Care Expert Panel
      on Enfuvirtide. The guidelines, including suggestions on assessment, education,
      and management of side effects are reviewed. Teaching tools and resources are
      offered to assist in patient management. In addition, suggestions for proper
      syringe disposal and traveling with enfuvirtide are offered.

PMID- 16438122
TI  - Bioimpedance analysis and HIV-related fatigue.
AB  - Although various physiological and psychological causes of fatigue in HIV
      positive persons have been proposed, it is still not well understood.
      Bioimpedance analysis has proved to be an easily used, non-invasive measurement
      of body composition and cellular integrity. This study, looking at whether body
      composition as measured by bioimpedance analysis is associated with fatigue, is
      part of a pilot study looking for physiological and psychological biomarkers that
      could be factors in the fatigue experienced by HIV-positive people. Twenty-nine
      men and eleven women were measured for height, weight, and bioimpedance analysis.
      Correlations were examined between fatigue intensity and weight, body mass index,
      body cell mass, fat-free mass, extracellular mass, and phase angle. Because of
      the fat redistribution that has occurred with some people taking protease
      inhibitors, we also examined differences in weight, body mass index, body cell
      mass, fat-free mass, and fatigue intensity between those taking and those not
      taking protease inhibitors. There was no association between fatigue intensity
      and weight, body mass index, body cell mass, fat-free mass, or phase angle, nor
      were there differences between those taking and those not taking protease
      inhibitors. However, it was noted that both the phase angle and the ratio of
      extracellular mass to body cell mass (extracellular mass:body cell mass) were
      below their respective normal ranges, indicating that the participants were
      somewhat compromised nutritionally and with regard to cell membrane integrity.
      Although fatigue was not shown to be related to body composition measurement in
      this study, further work is needed on the causes of fatigue, because its effects
      on the lives of HIV-positive people can be devastating.

PMID- 16438123
TI  - Designing a culturally based intervention to reduce HIV sexual risk for Latino
      adolescents.
AB  - There is a pressing need to develop effective interventions to prevent sexually
      transmitted HIV infection among Latino adolescents. Although there have been few
      models to direct the design of culturally effective interventions, the processes
      of recognizing the influence of specific cultural and contextual variables,
      building on "what works," and integrating community perspectives are important
      elements. These processes were used in the development of a Latino culturally
      based curriculum designed to reduce the risk of sexually transmitted HIV among
      Latino youth. Specific examples are provided to illustrate how these processes
      were used and how the curriculum evolved.

PMID- 16438124
TI  - The experience of African American women living with HIV: creating a prevention
      film for teens.
AB  - The personal and social costs of HIV are well documented. What remains unknown is
      the effect of public disclosure of HIV status on the individual who is doing the
      disclosing. This study describes the experience of four African American women
      living with HIV who participated in the development of an intergenerational
      education intervention for African American adolescent girls. These women
      suggested that they be filmed discussing the "dark side" of HIV in an effort to
      create an intergenerational education intervention that would alter the risk
      taking behavior that they observed in young women in their community. After a
      rough cut of the film was completed, these women viewed the film and participated
      in a focus group during which they discussed what it was like to reveal and
      revisit their own painful experiences associated with becoming infected and then
      living with HIV. Findings from content analysis of transcribed dialogue included
      the following positive themes: (a) self-acceptance by telling one's own story and
      hearing the stories of the other women, (b) a sense of liberation by disclosing
      publicly one's image and message and letting go of others' judgments, (c) feeling
      supported by meeting other women who share the same experience, (d) value of
      using the film to impact or save young people from the pain one has experienced.
      A negative theme emerged related to personal pain in reliving the individual's
      history with HIV.

PMID- 16438125
TI  - Education: an antidote for the spread of HIV/AIDS.
AB  - There are growing fears about the rate at which AIDS is spreading across the
      globe today, particularly in Africa. In 20 years, AIDS has become the greatest
      pandemic ever, and indications are that it will continue to increase. Because
      there is no universally accepted curative drug for the treatment of the epidemic,
      this report describes an attempt at providing education as a preventive method
      for the spread of the deadly disease. It is also an attempt to rise to this
      challenge by a systematic analysis of appropriate theories that can lead to
      insight into the epidemic. An empirical approach will further add to scholarly
      understanding and much-desired solutions. Suggestions are offered on how to
      achieve these goals through integration of HIV/AIDS education into school
      curricula, and how nursing practice can help in the education about and treatment
      of the disease. This report is the first part of a two-phased study from a
      sociologic point of view of an emergent universal health problem.

PMID- 16438126
TI  - An Ontario initiative to enhance the effectiveness of AIDS Service Organizations:
      Community-Linked Evaluation of AIDS Resources.
AB  - This report describes the rationale, process, and early outcomes of establishing
      a community-based research unit. The AIDS Bureau of the Ontario Provincial
      Government established the Community-Linked Evaluation of AIDS Resources Unit
      (CLEAR), which works in partnership with the AIDS Bureau and 31 of 74 AIDS
      Service Organizations (ASOs) in Ontario.

PMID- 16438127
TI  - CROI--the 12th Conference on Retroviruses and Opportunistic Infections: a report
      on the conference.

PMID- 16438128
TI  - Optimizing malarial epidemiological studies in areas of low transmission.
AB  - Malaria risk factor studies have traditionally used microscopy readings of blood
      slides as the measure of malaria infection in humans, although alternatives are
      available. There is the need for an assessment of how the use of these
      alternative diagnostic approaches will influence the efficiency and significance
      of epidemiological studies. In an area of Sri Lanka with known risk factors for
      malaria, two cross-sectional surveys were done at the start and at the peak of
      transmission season. Microscopy was compared with enzyme-linked immunosorbent
      assays (ELISA) and polymerase chain reaction (PCR). The major risk factor in this
      area was the location of houses relative to confirmed vector breeding sites. At
      the peak of the transmission season, the results pointed in the same direction,
      irrespective of the diagnostic method used. However, the importance of distance
      from the breeding site was not statistically significant when microscopy was
      used, which can be explained by the lower prevalence of microscopy positivity in
      comparison to the prevalence of ELISA- and PCR-positivity. This study suggests
      that in low-transmission areas, such as Sri Lanka, smaller sample sizes can be
      used for epidemiological research studies using PCR instead of microscopy to
      estimate parasite prevalence. This efficiency gain has to be weighed against the
      higher cost and complexity of the PCR. PCR cannot replace microscopy as the
      standard diagnostic procedure at the field level. ELISA is not directly
      comparable with microscopy and PCR but it can also be a useful tool in malaria
      epidemiological studies. This study indicates that cross-sectional surveys are
      only efficient if they take place during peak transmission season. Cross
      sectional surveys currently implemented by the Sri Lankan government in response
      to local malaria outbreaks can form the basis for valid epidemiological studies
      and be used for the generation of malaria risk maps if samples were also analyzed
      using PCR.

PMID- 16438129
TI  - An open randomized clinical trial of Artekin vs artesunate-mefloquine in the
      treatment of acute uncomplicated falciparum malaria.
AB  - Malaria remains a major cause of morbidity and mortality in tropical countries
      and subtropical regions in the world. Southeast Asia has the most resistant
      malaria parasites in the world, which has limited treatment options in this
      region. In response to this situation, short-course artemisinin-based combination
      therapies (ACTs) have been developed. The combination of dihydroartemisinin (DHA)
      and piperaquine (PQP) in the form of Artekin has been developed as an alternative
      to established combinations, such as artesunate-mefloquine, primarily to reduce
      treatment costs and toxicity. We conducted a study comparing a standard treatment
      for acute uncomplicated falciparum malaria (artesunate 4 mg/kg/day together with
      mefloquine 8 mg/kg/day oral route once a day for 3 days) (Group A) and a
      combination of dihydroartemisinin 40 mg and piperaquine 320 mg in the form of
      Artekin given once a day for 3 days (Group B) to determine safety, efficacy, and
      tolerability. One hundred and eighty patients were randomly enrolled at the ratio
      of 1:2 into groups A:B. All patients had rapid initial clinical and
      parasitological responses. There were no significant differences in fever
      clearance time or parasite clearance time between both groups. The 28-day cure
      rates were high, at 100% and 99%, in groups A and B, respectively. We conclude
      that Artekin was as effective and well-tolerated as artesunate-mefloquine, and
      can be used alternatively as the current treatment for multidrug-resistant P.
      falciparum malaria.

PMID- 16438130
TI  - Pyrimethamine-sulfadoxine treatment of uncomplicated Plasmodium falciparum
      malaria in Lao PDR.
AB  - A 28-day in vivo treatment trial to evaluate the efficacy of
      pyrimethamine/sulfadoxine (Fansidar, PS) was conducted in 21 Lao patients with
      uncomplicated Plasmodium falciparum malaria. Sixteen patients (76%) were
      completely cured with PS without any reappearance of asexual stage parasitemia
      during the follow-up examination. On the other hand, 5 patients (24%) failed to
      respond to this trial medication, resulting in recrudescence of asexual stage P.
      falciparum malaria. PS resistance resulted in higher prevalence of post-treatment
      gametocytemia, 25% gametocyte carriers among PS sensitive cases versus 75% of the
      resistant cases. These findings suggest that although the level of PS resistance
      is still valid for treatment of malaria in the study area of Lao PDR, post
      treatment induction of gametocytemia among resistant cases may result an increase
      in transmission rate of PS resistant falciparum malaria.

PMID- 16438131
TI  - The ultrastructure of the gravid uterus of Brugia pahangi, another rich source of
      antigen of the filarial parasite.
AB  - The gravid uterus with zygotes and microfilariae in utero of Brugia pahangi, a
      rich source of antigen as revealed by a recent immunofluorescent technique, were
      studied ultrastructurally. The epithelial cells of uterus show ultrastructural
      features of synthetically active cells. Their secretions may provide nutrients
      for the egg in utero. On the basal side, the uterine epithelial cells may also
      secrete substances to form the basal lamina of the uterus which is rather thick
      and irregularly fused with the basal lamina lining the body wall where the
      pseudocoelomic cavity is obliterated. For the most part, the uterine basal lamina
      contains uniform granular material of moderate electron density. There are also
      elongated visceral muscle cells embeded in it, and which surround the uterus,
      with adjacent cells overlapping. The gravid uterus contains several stages of
      developing microfilariae within its lumen, the cleaving zygotes are also present
      at another level. The morula of zygotes are composed of several closely packed
      cells surrounded loosely by their own egg shell membranes. The egg shell becomes
      more convoluted as development proceeds. The egg shell surrounding the developing
      microfilariae in utero is secreted by the uterine epithelium. This structure
      later becomes the sheath of circulating microfilariae, and is highly antigenic as
      indicated by intense labeling with fluorescent antibodies.

PMID- 16438132
TI  - The efficacy of a single-oral-dose administration of ivermectin and
      diethylcarbamazine on the treatment of feline Brugia malayi.
AB  - The combination of ivermectin and diethylcarbamazine (DEC) have been shown to be
      superior to either drug alone for the suppression of Brugia malayi in humans, but
      their efficacy against infection with B. malayi in cats has never been
      investigated. Fourteen asymptomatic microfilaremic (1-200 microfilariae/20 microl
      blood) cats received oral doses of ivermectin (400 microg/kg body weight) and DEC
      (6 mg/kg body weight) as a single treatment. A two-month post-treatment
      examination revealed that 87-100% of the microfilariae in each subject had been
      cleared, with two of the subjects being amicrofilaremic. A further reduction in
      microfilarial levels was observed until the final follow-up, at 8 months post
      treatment, when the mean clearance rate was 99% and 12 out of the 14 subjects
      (86%) were amicrofilaremic. The combination of ivermectin and DEC demonstrated a
      microfilaricidal effect superior to that of either drug used alone, both in the
      initial rapid clearance of microfilariae, and in sustaining the effect for 8
      months. This finding has important implications for the control of brugian
      lymphatic filariasis in the cat reservoir.

PMID- 16438133
TI  - Determination of fecal occult blood in primary schoolchildren infected with
      Trichuris trichiura.
AB  - A correlation of Trichuris trichiura infection and fecal occult blood detection
      was conducted in 146 primary schoolchildren in Narathiwat Province, Thailand. The
      Kato-Katz thick smear method was used for determining egg counts and stated as
      eggs per gram of feces (epg). The number of T. trichiura eggs was categorized as
      class I (1-499 epg), class 11 (500-4,999 epg), and class III (> 5,000 epg),
      according to the relation between infection intensity and reduced hemoglobin
      concentration. Each fecal sample was processed to detect occult blood using a
      guaiac-based test (Hema-Screen, USA) and an immunochromatographic-based test
      (HEXAGON OBTI test, Germany). There were 50 schoolchildren without parasitic
      infection in the control group. Of 96 cases with T. trichiura infection, 85 and
      11 children were classified in the class I and class II groups, respectively, but
      no subjects were in the class III group. Positive occult blood detection results
      in the control, class I, and class II groups using the guaiac and the
      immunochemical tests were 0, 3.5, and 9.1% (p=0.19), and 0, 2.4, and 36.4%,
      (p<0.0001) respectively. This study suggests that T. trichiura infection with an
      intensity of 500 epg or greater may be associated with intestinal bleeding.

PMID- 16438134
TI  - Investigation on the epidemiological factors of Clonorchis sinensis infection in
      an area of south China.
AB  - To detect the epidemiological factors of Clonorchis sinensis infection in
      Hengxian County, one of counties in Guangxi Zhuang Autonomous Region where
      Schistosoma japonicum was endemic but eliminated in the late 1980s, a
      questionnaire was designed with 37 questions covering socioeconomic conditions
      and human behavior, contamination of the environment and fish ponds, inadequate
      farming/fishery practices; and the formalin-ether sedimentation technique was
      used to examine the feces of cats, dogs and pigs for the eggs of C. sinensis.
      Fresh fish was sliced and digested to detect the metacercariae of C. sinensis
      under a stereomicroscope. Of 1,521 people interviewed, 64% of the interviewees
      did not know about fluke disease or its transmission route, 46% of those who knew
      about the fluke believed that the infection caused no harm or only slight harm to
      their health. More than half of the interviewees (51%) ate raw fish at least 1-2
      times per month, more among the middle-aged males. Eight percent of them used the
      same utensils for both raw fish and cooked food. When advice was given not to eat
      raw fish, 73% of the interviewees thought it was not feasible. In relation to
      pisciculture, 25% and 9% of the owners of fish ponds fed their fish with feces of
      domestic animals and human feces, respectively. The prevalences of C. sinensis
      infection in cats, dogs and pigs were 70, 50 and 27%, respectively, and the
      infection rate in fish was 40%. These results indicate the poor knowledge, and
      beliefs, and unhealthy behaviors in the human population. They also show poor
      environmental hygiene and inappropriate farming/fishery practices are important
      in the increase of C. sinensis prevalence in humans. Combined interventions,
      including health education, environmental modification, reform of traditional
      farming/fishery practices, mass screening and chemotherapy for humans, and the
      management of domestic animals are needed in developing control strategies to
      decrease C. sinensis infection in the human population.

PMID- 16438135
TI  - Comparative studies on the pathological findings and mortality in Schistosoma
      mansoni infected mice after treatment with artesunate and the current
      antischistosomal drugs.
AB  - The effect of artesunate (ART) on the pathology and mortality rate of in
      Schistosoma mansoni infected mice was comparatively studied with the current
      drugs of choice for the treatment of schistosomiasis mansoni: praziquantel (PZQ)
      and oxamniquine (OX). S. mansoni experimentally infected mice were treated at 9th
      week of infection with ART, PZQ or OX at an oral dosage of 300 mg kg(-1), 600 mg
      kg(-1) and 100 mg kg(-1), respectively. Untreated, infected mice and non-infected
      mice were added as controls. Samples of mice were sacrificed and examined for the
      pathological findings at 1 week, 1 month, and 3 months after treatment. At 1 week
      after treatment, both gross and microscopic lesions were observed. No significant
      differences were noted among the infected groups. Differences were observed at 1
      month after treatment. The lesions decreased more rapidly in groups treated with
      PZQ and OX. At 3 months after treatment, there were significant differences in
      the pathological findings among groups. In the groups treated with PZQ and OX,
      the lesions were markedly reduced and rarely found, but they were clearly
      observed in the group treated with ART and in the untreated, infected group. High
      mortality was also recorded in the group treated with ART and in the untreated,
      infected group. Therefore, the treatment of S. mansoni infected mice at 9 weeks
      of infection with ART did not reduce the pathological findings or the mortality
      rate compared to treatment with the current recommended schistosomicides, PZQ and
      OX.

PMID- 16438136
TI  - A survey of ectoparasites in Gunung Stong Forest Reserve, Kelantan, Malaysia.
AB  - A survey of ticks and other ectoparasites was carried out during a national
      biodiversity scientific expedition at Gunung Stong Forest Reserve, Kelantan,
      Malaysia from 23-29 May 2003. A total of 272 animals comprised of 12 species of
      birds, 21 species of bats, 7 species of rodents and 2 species of insects were
      examined for ticks and other ectoparasites. From these animals, 5 species in 4
      genera of ticks; 7 species in 2 families of Mesostigmatid mites and 5 species of
      chiggers were collected. Among the ectoparasites found were Ixodes granulatus and
      Leptotrombidium deliense, which are of known medical importance. A tick island
      consisting of 10 nymphal stages of Dermacentor spp was observed feeding on Rattus
      tiomanicus.

PMID- 16438137
TI  - Differential environmental preferences of gravid female Aedes mosquitoes in
      ovipositing their eggs.
AB  - A prospective field study was carried out to investigate any preferential
      differences of gravid female Aedes mosquitoes in ovipositing their eggs in man
      made containers placed in different environmental conditions. The findings of
      this study show that gravid female Aedes mosquitoes preferred to breed in
      containers found in the outdoor garden than those placed on the patio and or
      inside the house. The findings also show that if the breeding habitats in the
      garden were removed, they would favorably use the breeding habitats found on the
      patio or inside the house as alternatives. An incidental interesting finding in
      this study shows that ultra-low volume fogging of insecticides using the vehicle
      mounted equipment carried out outside the house may promote the gravid female
      Aedes mosquitoes to enter the house to breed.

PMID- 16438138
TI  - Effect of temperature and insecticide stresses on Aedes aegypti larvae and their
      influence on the susceptibility of mosquitoes to dengue-2 virus.
AB  - Two major factors, higher temperatures and the application of insecticides, can
      drastically alter the genetic structure of a vector mosquito population. Due to
      these two stresses, the majority of the population gets wiped out, but the ones
      that withstand the stress and survive are likely to pass on survivability, and
      have an altered physiology. Our study shows that exposures to higher temperatures
      and DDT during the larval stage affects their susceptibility as adult mosquitoes
      to the DEN-2 virus. The overall transcription and translation status of heat
      shock protein (Hsp70) in virus high- and low-susceptible was the same as that in
      other batches. In the case of a DDT-resistant (R-7) strain two bands were
      obtained during RT-PCRs after heat shock. These two alleles were obtained only
      with HY-1 in which R-7 males were used for the crosses, suggesting that the
      second allele is probably male sex linked. The higher expression of Hsp70 may
      provide DDT-resistant strains a better chance of survival high temperature
      environments, particularly in homozygotes and hybrids. It was also interesting to
      note that these strains have a significantly lower susceptibility to the virus.
      Wide-spread DDT-resistance and a rise in temperature above the average
      temperature during summer may result in a population with a low susceptibility to
      the virus. Several families of heat shock proteins are known to be expressed in
      mosquitoes, and may have a cumulative role in determining susceptibility to the
      virus, which itself is governed by several genes.

PMID- 16438139
TI  - Use of a remote sensing-based geographic information system in the characterizing
      spatial patterns for Anopheles minimus A and C breeding habitats in western
      Thailand.
AB  - A remote sensing (RS)-based Geographic Information System (GIS) was used to
      characterize the breeding habitats of Anopheles minimus species A and C in five
      different districts of Kanchanaburi Province in western Thailand. The GIS and RS
      were used to monitor the area for the presence and absence of An. minimus A and C
      in five major land areas, forest, agriculture, urban, water and bare land. The
      results show that An. minimus A survives both in dense canopy forest and in open
      fields where agriculture is dominant. A scatter plot of land-use/land-cover for
      An. minimus, considering proximities to the forest and proximities to
      agriculture, suggests that An. minimus A has a wider habitat preference, ranging
      from dense canopy forest to open agricultural fields. A scatter plot for An.
      minimus C, on the other hand, showed a narrow habitat preference. A scatter plot
      for proximities performed on separate populations of An. minimus species A, one
      in the north and the other in the south, showed that there was an association in
      the northern population with the forest and in the southern population with
      agricultural areas. There were no statistically significant differences in the
      scatter plot of proximities to urban areas and water bodies with the An. minimus
      A north, south, and An. minimus C. LANDSAT TM satellite data classification was
      used to identify larval habitats that produce An. minimus A and C and analyze
      proximities between land-use/land-cover classes and locations of larval habitats.
      An. minimus A has a wide habitat preference, from dense canopy forest to open
      agricultural fields, while An. minimus C has a narrow habitat preference.

PMID- 16438140
TI  - Soil analysis around anopheline breeding habitats in north-western Thailand.
AB  - The epidemiology of malaria is largely dependent on its vector habitat. Each
      species of Anopheles larvae has a specific habitat requirement for its
      development. Anopheline mosquitoes are common throughout Thailand and utilize a
      wide variety of habitats. The dominant malaria vectors in Thailand are An. dirus,
      An. maculatus, and An. minimus. The relationship between soil chemical components
      and the particular species of anopheline in their specific aquatic habitats was
      studied from September 2002 to July 2003 at Ban Khun Huay, Ban Pa Dae, and Ban
      Tham Seau in the Mae Sot district, Tak Province, Thailand. Mapping of each
      habitat was performed using a Global Positioning System unit. A total count of
      2,130 laboratory reared adult Anopheles were collected from 138 habitats
      categorized into 11 different types identified into 18 species from larval
      sampling in three villages. An. dirus, An. maculatus, and An. minimus were found
      5.26%, 10.70%, and 55.31%, respectively, along with other minor species. Drainage
      and/or season seemed to be associated with the presence of An. dirus, An.
      maculatus, An. minimus, An. jamesii, An. sawadwongporni, and An. peditaeniatus.
      Chemical tests: pH, aluminum, magnesium, calcium, and ferric iron showed some
      associations with the presence of Anopheles. Only drainage was found to be a
      parameter associated with the presence of An. minimus.

PMID- 16438141
TI  - Sequence analyses of three nuclear ribosomal loci and a mitochondrial locus in
      cytologically different forms of Thai Anopheles aconitus mosquitoes.
AB  - Ribosomal DNA (rDNA) and mitochondrial DNA (mtDNA) of Anopheles aconitus
      mosquitoes were examined to investigate intra- and inter-species variation
      amongst the members of the Minimus group of Anopheles subgenus Cellia. Three rDNA
      loci (ITS1, ITS2 and D3 regions) and a mtDNA locus (cytochrome oxidase II) were
      analyzed in An. aconitus Form B and Form C collected in Chiang Mai Province,
      Thailand. The results show that the consensus sequences of the four loci of the
      two forms are consistent with those of mosquitoes in the genus Anopheles. No
      intraindividual variation was detected, but intrapopulation variation was present
      with polymorphic sequences in some forms for each gene examined. The variation
      rates were approximately 0.15 to 0.8%. These data indicate that An. aconitus Form
      B and Form C in Chiang Mai, Thailand are conspecific. In this study, the complete
      ITS1 sequence of An. aconitus is reported for the first time. The region showed a
      high variation rate (approximately 55%), compared to the closely related species
      An. minimus C. It is suggested that this rDNA locus may provide sequence
      information to differentiate the members of the Minimus group of Anopheles
      subgenus Cellia.

PMID- 16438142
TI  - The 2003 outbreak of Dengue fever in Delhi, India.
AB  - Dengue fever (DF) and Dengue hemorrhagic fever (DHF) are widespread in Southeast
      Asia. An outbreak of DF/DHF in Delhi in 2003 started during September, reached
      its peak in October-November, and lasted until early December. This study
      describes the clinical and laboratory data of the 185 cases of DF/DHF admitted to
      Lok Nayak Hospital, New Delhi. The mean age of the patients was 26 +/- 10 years.
      Fever was present in all the cases with an average duration of fever being 4.5 +/
      1.2 days with headache (61.6%), backache, (57.8%), vomiting (50.8%) and
      abdominal pain (21%) being the other presenting complaints. Hemorrhagic
      manifestations in the form of a positive tourniquet test (21%), gum bleeding and
      epistaxis (40%), hematemesis (22%), skin rashes (20%) and melena (14%) were also
      observed. Hepatomegaly and splenomegaly were observed in 10% and 5% of cases,
      respectively. Laboratory investigations revealed thrombocytopenia (with a
      platelet count of < 100,000/microl) in about 61.39% of cases, Leukopenia (WBC
      <3,000/mm2) and hemoconcentration (Hct >20% of expected for age and sex) were
      found in 68% and 52% of the cases, respectively. The mortality rate was 2.7%.
      Despite widespread measures taken to control outbreaks of DF, it caused major
      outbreaks. More stringent measures in the form of vector control, improved
      sanitation and health education are needed to decrease morbidity, mortality and
      health care costs caused by a preventable disease.

PMID- 16438143
TI  - A review of dengue fever incidence in Kota Bharu, Kelantan, Malaysia during the
      years 1998-2003.
AB  - Dengue is the most common and widespread arthropod borne arboviral infection in
      the world today. It is estimated that there are at least 100 million cases of
      dengue fever (DF) annually and 500,000 cases of dengue hemorrhagic fever (DHF)
      which require hospitalization. In Malaysia, it has become a major public health
      problem. Malaysia recorded 19,544 dengue cases in 1997, the highest recorded
      since the disease was made notifiable in the country. Of 19,544 cases, 806 were
      DHF with 50 deaths. The objectives of this analysis were to describe the
      incidence of dengue fever and dengue hemorrhagic fever in Kota Bharu, Kelantan,
      Malaysia for the years 1998-2003 and to explore the characteristics of dengue
      fever and dengue hemorrhagic fever in Kota Bharu, Kelantan, Malaysia for years
      1998-2003. A total of 4,716 dengue cases were notified involving 4,476 (94.9%) DF
      and 240 (5.1%) DHF cases, which increased though the years. The highest incidence
      was in January (701 or 14.9%), while the lowest was in May (188 or 4.0%). Forty
      percent of cases (n=1,890) were in the 15-29 year old group. The Majority were
      Malays (4,062 or 86.1%) and 2,602 or 55.2% were male. A total of 4,477 cases
      (95%) were local cases and 4,289 or 91% came from the urban area. For priority
      areas, 3,772 (80%) were from priority 1. More than half the cases had positive
      serology results. All symptoms occurred in more than 96% of cases and fever was
      the commonest (99.7%). The mean values for age, temperature, systolic and
      diastolic blood pressure (BP) were 27.8 +/- 15.4 years, 37.9 +/- 0.90 degrees C,
      115 +/- 15.2 mmHg and 73 +/- 11.1 mmHg, respectively. The mean value for the time
      interval between the onset of symptoms and diagnosis, onset of symptoms and
      notification and time of diagnosis to notification were 5.1 +/- 2.3, 5.9 +/- 2.5
      and 0.8 +/- 1.1 days, respectively. There were associations between the types of
      dengue and classification, area and priority area. Among the symptoms, the
      association was only seen in joint pain. The mean significant differences between
      DF and DHF were found in age and systolic blood pressure. The incidence of dengue
      in Kota Bharu is comparable to that in Malaysia. The increase in the number of
      cases needs to be addressed promptly with effective surveillance, prevention and
      control programs.

PMID- 16438144
TI  - Genetic variations and relationship among dengue virus type 3 strains isolated
      from patients with mild or severe form of dengue disease in Indonesia and
      Thailand.
AB  - Sequence analysis was conducted on structural and non-structural genes of 7
      strains of dengue virus type-3 (DENV-3 virus) isolated in Indonesia and Thailand
      in the year 1973, 1994, and 1998 from patients with different clinical
      manifestations. In general, sequence similarity among isolates was greater than
      93%, indicating that the mutation rate of DENV-3 circulating in this region was
      not more than 7% in the last 3 decades and suggesting that sequences that may
      responsible for viral architectures and/or biological function were strictly
      conserved. Mutations unique to viral strains associated with specific clinical
      manifestations were not found. Alignment of PrM/M and E nucleic acid sequences
      followed by parsimony analysis of sequences obtained in this study and published
      elsewhere allowed generation of phylogenetic trees, demonstrating that DENV-3
      strains isolated in Indonesia in 1998 belonged to a separate cluster (subtype 2)
      from those isolated between 1973-1985 (subtype 1).

PMID- 16438145
TI  - Survey on the management of dengue infection in Sri Lanka: opinions of physicians
      and pediatricians.
AB  - The management of dengue infection is variable and clinicians often adopt their
      own methods based on clinical experience. Hence, there is a lack of uniformity in
      the practice and management of dengue fever (DF) and dengue hemorrhagic fever
      (DHF) in Sri Lanka. The objectives were to describe the opinions of clinicians
      regarding certain management issues of, and their clinical experiences in DF/DHF.
      A self-administered questionnaire survey of 50 consultant physicians and
      pediatricians that were currently practicing in Government Hospitals was
      conducted. Their cumulative experience was based on managing approximately 15,119
      patients for a period of three years in 15 districts of the island. The WHO
      guidelines were used by only 16(45%) physicians and 6(40%) pediatricians in the
      management of DF/DHF Most of the clinicians did not agree on the value of
      steroids and antibiotics. However, the majority was in favor of platelet and
      plasma transfusions, although most had no fixed policy on fluid management. In
      the experience, clinicians observed the recurrence of dengue, post-viral fatigue
      syndrome, and many other complications. A conclusion was made that a national
      policy and guidelines should be created to suit the local context, based on the
      evidence and experiences of clinicians managing dengue infection.

PMID- 16438146
TI  - A seroepidemiology study of varicella among children aged 0-12 years in Taiwan.
AB  - The epidemiology pattern of varicella appears to vary among regions with
      different climates, population densities, and degrees of development. This study
      investigated the age-specific varicella zoster virus (VZV) seroprevalence in
      children aged 0 to 12 years in Taiwan and compared these seroprevalences between
      free and private vaccination areas. Residual sera were collected from 13
      hospitals with 1,401 valid samples. Immunoglobulin G antibodies to VZV were
      measured by enzyme-linked immunosorbent assay. Parents of 656 children answered
      questions about the varicella incidence and varicella vaccination history of
      their children. In the 8-12 year-olds, the seroprevance ranged between 88.0-93.8%
      in northern, central, and eastern, while it was only 76.1% in southern Taiwan.
      The seroprevalence of children 0-5 years old were significantly different between
      free and private vaccination areas. Seropositive children who reported no history
      of varicella or receiving varicella vaccine accounted for 26.1-59.3% of the total
      positive cases. Our findings suggest the possible effects of climate,
      geographical conditions, and lifestyle on the seroepidemiology of VZV in Taiwan.
      The efforts of implementing a varicella vaccination program in Taiwan should
      focus on reaching high levels of coverage.

PMID- 16438147
TI  - Physician adherence to isoniazid preventive therapy guidelines for HIV-infected
      patients in Thailand.
AB  - Isoniazid preventive therapy (IPT) has been shown to reduce the risk of active
      tuberculosis in tuberculin skin test (TST) positive human immunodeficiency virus
      (HIV) infected individuals. The World Health Organization has recommended IPT for
      HIV-infected patients since 1999. Physicians' non-adherence to the IPT guideline
      is one of the limitations to the wide spread use of IPT. A study of the extent to
      which physicians in Thailand adhere to this guideline will optimize the
      implementation of national IPT program. Three hundred physicians who provided
      medical care for HIV-infected patients were sampled by multistage cluster
      sampling of public hospitals according to the region and the level of health care
      service. Fifty-eight (19.3%) of the surveyed physicians provided IPT; 86.2% and
      34.5% of physicians who provided IPT did not do the TST or screening chest
      radiography for active TB, respectively. Experience with HIV patient care was
      significantly associated with providing IPT.

PMID- 16438148
TI  - Parvovirus b19 infection in HIV patient with pure red cell aplasia.
AB  - Anemia in HIV-infected patients is a common clinical manifestation. We report on
      a 31-year-old Thai male, who had been HIV positive for 6 years, did not harbor
      any opportunistic infection, and had been receiving Highly Active Anti Retroviral
      Therapy (HAART) for one month, and who developed severe anemia. Investigation
      revealed pure red cell aplasia, suspected secondary to parvovirus B19 infection.
      This diagnosis was confirmed by the detection of parvovirus B19 DNA in his serum.
      He received blood transfusions for supportive treatment and continued on HAART to
      improve his immune status and to resolve the anemia. This case suggests that
      parvovirus B19 infection should be considered as a possible cause of anemia in
      HIV-infected individuals.

PMID- 16438149
TI  - Analysis of three phenotyping methods and pulsed-field gel electrophoresis for
      differentiation of methicillin resistant Staphylococcus aureus isolated from two
      hospitals in Thailand.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is an important hospital and
      community-acquired pathogen. Rapid and reliable epidemiologic typing is necessary
      for controlling the spread of MRSA outbreak. The objective of this study was to
      compare the phenotyping with the genotyping method to differentiate MRSA isolates
      obtained from the two hospitals in Thailand (central and northeastern). Seventy
      four MRSA isolates were randomly collected and confirmed by the presence of mecA
      gene. Antibiogram, phage typing and enterotoxin production were used for the
      phenotyping analysis. Pulsed-field gel electrophoresis (PFGE) with Smal digestion
      of chromosomal DNA was used for the genotyping analysis. We found 17 distinct
      profiles by the 3 phenotypic typing methods and 18 PFGE types designated as 5
      major types (A-E) and 13 subtypes. The most frequent PFGE types and their related
      subtypes found in both hospitals were A and C, comprising 54 and 27%,
      respectively. The antibiogram could differentiate 6 different types. All isolates
      were resistant to the majority of antimicrobial agents tested, but were
      susceptible to vancomycin and fosfomycin. Ten (13.5%) MRSA isolates produced
      enterotoxin A. Nontypable phage and phage type 77 were found predominantly in
      MRSA isolated from the northeast and central hospital, respectively. A
      significant correlation was found between the phenotyping and the genotyping
      methods and there was a good correlation between antibiogram and PFGE.
      Antibiogram typing alone can be used as a useful epidemiological marker for
      practical purposes. PFGE types A and C were the common endemic MRSA clones in
      both hospitals in Thailand.

PMID- 16438150
TI  - An enrichment broth culture-duplex PCR combination assay for the rapid detection
      of enterotoxigenic Clostridium perfringens in fecal specimens.
AB  - An enrichment broth culture-duplex PCR combination assay was devised to identify
      Clostridium perfringens directly from fecal samples. The method consists of a
      combination of short enrichment of samples in selective media, DNA isolation, and
      performing duplex PCR using two pairs of primers which identify C. perfringens
      strains that harbor the virulence enterotoxin gene. Comparison of two selective
      enrichment media and two incubation temperatures showed that the reinforced
      clostridial medium with neomycin was better than the fluid thioglycollate medium
      with neomycin (p<0.001); and incubation at 37 degrees C vs 45 degrees C showed no
      statistically significant difference (p=0.238). The optimal short time for pre
      enrichment culture was 4 hours. The developed assay was applied to detect
      phospholipase C (plc) and enterotoxin (cpe) genes for C. perfringens in feces
      inoculated artificially with enterotoxigenic C. perfringens. The method could
      detect both gene products in samples inoculated with a minimum of 10(4) CFU per
      ml. When the method was applied to detect enterotoxigenic C. perfringens in 198
      diarrhea patients, C. perfringens was found in 121 samples; 7 out of 121 samples
      were positive for both plc and cpe (prevalence of 5.8%). These results indicate
      that the developed assay was a suitable method for the rapid and specific
      detection of enterotoxigenic C. perfringens directly in fecal specimens of
      diarrhea patients, which will assist epidemiological investigations of food
      poisoning outbreaks and quality control of food products.

PMID- 16438151
TI  - In vitro activity of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin
      imipenem and ceftazidime-gentamicin combinations against ceftazidime-resistant
      Pseudomonas aeruginosa.
AB  - The effects of antimicrobial combinations against ceftazidime-resistant
      Pseudomonas aeruginosa strains isolated from hospitalized patients were
      investigated. Using the checkerboard titration method, combination of fosfomycin
      gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime
      gentamicin was synergistic against 4, 11, 38 and 39% of 22, 18, 29 and 18 strains
      tested respectively and additive effect of the combinations against the strains
      tested was 41, 33, 14 and 44%, respectively. Antagonistic effects against the
      isolates were noted when fosfomycin was combined with gentamicin (27%),
      ceftazidime (22%) and imipenem (7%). No antagonistic effect was observed in the
      ceftazidime-gentamicin combination.

PMID- 16438152
TI  - Etiology of obscure fever in children at a university hospital in northeast
      Thailand.
AB  - Obscure fever is not an uncommon problem in Thailand. We studied 25 children with
      obscure fever admitted to Srinagarind (university) Hospital in Northeast
      Thailand. The etiology was identified in 52% of the cases: dengue (40%),
      leptospirosis (8%), and micrococcus septicemia (4%). Two cases with primary
      dengue infection developed dengue shock syndrome. The case with leptospirosis
      developed infection-associated, hemophagocytic syndrome. We found no cases of
      Japanese encephalitis, scrub typhus or murine typhus.

PMID- 16438153
TI  - Pulmonary radiographic findings in 118 leptospirosis patients.
AB  - We retrospectively reviewed the medical records and chest radiographs of 118
      patients who presented during January 1998 to October 2002 at Songklanagarin
      Hospital in Hat Yai, Songkhla Province, Thailand who had a high serum
      immunofluorescent assay titer for leptospirosis. Twenty-nine of 118 (24%)
      patients had abnormal chest films. Nearly all of these patients had respiratory
      symptoms and needed oxygen therapy (93% and 90%, respectively). Forty-eight of
      the 118 (40%) had respiratory symptoms, but only 27/48 (56%) had abnormal
      radiographs. Twenty-one of the 28 (75%) and 18/27 (67%) who had abnormal chest
      radiographs had coexisting impaired renal function or jaundice, respectively,
      whereas 21/69 (30%) of the patients who had impaired renal function and 18/55
      (33%) of the patients with jaundice had abnormal radiographs. There were 6/27
      (22%) patients who had abnormal chest radiographs without renal or liver
      impairment. The most common finding on the abnormal chest radiograph was
      bilateral diffuse air space disease, which resolved within 7 days. No permanent
      lung damage was seen. The patients who had an abnormal chest radiograph needed
      longer hospitalization, than those without an abnormal chest radiograph (average
      12 days and 5 days, respectively).

PMID- 16438154
TI  - Evaluation of polymerase chain reaction and restriction enzyme analysis for
      routine identification of mycobacteria: accuracy, rapidity, and cost analysis.
AB  - Polymerase chain reaction and restriction enzyme analysis (PCR-REA) of the hsp65
      gene was evaluated for use as a routine identification method for identifying
      mycobacteria. The accuracy, rapidity, and cost were assessed compared with the
      conventional biochemical method. Five hundred and forty-one mycobacterial
      clinical isolates obtained from the Department of Microbiology, Faculty of
      Medicine at Siriraj Hospital, Mahidol University, were submitted for PCR-REA and
      biochemical identification. PCR-REA showed high concordant result with 100, 96.2,
      and 94.1% for identification of Mycobacterium tuberculosis, rapid- and slow
      growing mycobacteria, respectively. Discordant results were obtained from 24
      (4.4%) out of 541 isolates, consisting of 9 rapid growers (6 M. chelonae, 2 M.
      abscessus, and 1 M. fortuitum) and 15 slow growers (9 M. scrofulaceum, 2 M.
      gordonae, 1 M. avium, 1 M. kansasii, 1 M. malmoense, and 1 M. terrae complex).
      PCR-REA demonstrated not only accurate results but was also less expensive (2.1
      US dollars/sample). This method was rapid with a turn-around time of 30 hours
      compared with 2-4 weeks for the conventional method.

PMID- 16438155
TI  - Etiologies and treatment outcomes for out-patients with community-acquired
      pneumonia (CAP) at Srinagarind Hospital, Khon Kaen, Thailand.
AB  - Most patients with community-acquired pneumonia are treated as out-patients with
      empirical therapy, since initially the etiologic agent is unknown. We
      prospectively assessed the etiologies and treatment outcomes of pneumonia from
      February 2003 to 2004 at ambulatory clinics. Forty-four patients were included
      with a mean age of 49.2 (SD 18.2) years. The male to female ratio was 1:1.4. The
      incubation period was 6.9 (SD 4.4) days. Half of the patients were healthy.
      Asthma and COPD were common in patients with underlying diseases. The etiologic
      diagnosis was determined by a sputum culture and a serology test of paired serum
      samples. Hemo-culture produced no growth in any patients. Atypical pathogens and
      H. influenzae were the most common finding, each occurring in 31.8% of the
      patients followed by S. pneumoniae and H. parainfluenzae (27.3% each). Twenty-two
      patients were infected with multiple pathogens. C. pneumoniae was the most common
      co-infecting pathogen. Two of 12 S. pneumoniae isolates were penicillin
      resistant. Nine of 14 H. influenzae isolates were cotrimoxazole resistant and 8
      of 14 were not sensitive to erythromycin. For H. parainfluenzae, 11 of 12
      isolates were not sensitive to erythromycin, and 7 of 12 were not sensitive to
      cotrimoxazole. Oral antibiotics were prescribed as out-patient treatment. Forty
      patients (90.9%) improved, with symptoms-score improvement averaging 6.4 days.
      Four patients got worse and needed a change of antibiotics, the symptoms usually
      worsen within 3-5 days. We conclude that, antibiotics for CAP out-patients should
      cover atypical pathogens, H. influenzae, S. pneumoniae and H. parainfluenzae. If
      the clinical symptoms do not respond after 3-5 days of out-patient treatment,
      resistance or an unusual organism (eg B. pseudomallei) should be considered.

PMID- 16438156
TI  - Pulmonary actinomycosis presenting with prolonged fever and massive hemoptysis: a
      case report.
AB  - We present a rare case of pulmonary actinomycosis complicated with massive
      hemoptysis. The patient was a 41-year-old male farmer, who had experienced
      prolonged fever and off-and-on blood streaked sputum for 2 years. He was admitted
      to our hospital because of 3 days of massive hemoptysis. He had no underlying
      medical illnesses, but was a heavy smoker and an alcoholic. The chest radiograph
      revealed patchy alveolar infiltration of the right upper lobe, mimicing
      tuberculosis. Massive hemoptysis was not controlled using conservative treatment
      and anti-tuberculous drugs. Emergency right upper lobe lobectomy was needed to
      stop the bleeding. Histopathologic examination demonstrated aggregates of
      filamentous gram-positive organisms in characteristic "sulfur granules",
      indicating actinomycosis. The fever subsided after intravenous augmentin was
      given, followed by 6 months of oral amoxicillin. The patient is doing well and
      has had no recurrent hemoptysis.

PMID- 16438157
TI  - The first reported cases of disseminated histoplasmosis in Cambodia, complicated
      by multiple opportunistic infections.
AB  - Although disseminated histoplasmosis is recognized as a common opportunistic
      infection in HIV-infected persons living in endemic areas, it is not widely
      reported in Southeast Asia, and has not been reported in Cambodia. It remains
      unanswered whether this is secondary to a low disease prevalence, or whether the
      disease, which is associated with a nonspecific clinical presentation, is under
      diagnosed. In addition to a review of the literature regarding histoplasmosis in
      Southeast Asia, we provide a description of two HIV-1 infected patients with
      documented disseminated histoplasmosis complicating other opportunistic
      infections in Phnom Penh, Cambodia. These two cases highlight the need for both a
      high clinical suspicion, and reliable laboratory testing, in a setting where
      there is likely to be more than one infection complicating the patient's clinical
      course.

PMID- 16438158
TI  - Chronic illnesses in rural and remote Queensland communities using two sample
      units.
AB  - The objective of this study is to report the prevalence rates of chronic diseases
      using two sampling units: (a) the rural and remote areas of the Queensland
      Fitzroy and Central West Statistical Divisions and (b) four rural communities
      within the Queensland Fitzroy Statistical Division. The design was a cross
      sectional survey. The setting was rural and remote Queensland. The first sample
      unit was 641 households stratified and randomly selected from a commercial
      electronic database of 36,423 telephone numbers. Of these 641 households, 270
      agreed to take part. One respondent from each household provided information,
      including chronic illnesses, for all 697 household members. The second sample
      unit was all 356 households in four small rural communities. Of these, 223 agreed
      to provide information regarding 594 household members. The main outcome measures
      were the age and gender distribution of two sample groups and the prevalence
      rates of chronic illnesses. The people of the first sample unit had a
      significantly lower proportion of university or college graduates compared with
      the people in the second sample unit. There was a lower prevalence rate of asthma
      among people in the first unit than the rate reported by people in the second
      unit.

PMID- 16438159
TI  - Application of log-linear models to cancer patients: a case study of data from
      the National Cancer Institute.
AB  - Cancer is a noninfectious disease which is on the increase throughout the world
      and has become a serious problem for public health in many countries, including
      Thailand. In Thailand, cancer has risen significantly to become a leading cause
      of death and most patients are admitted to the National Cancer Institute. The
      objective of this study is to identify the associated factors between personal,
      cancer/clinical variables of cancer patients using log-linear models. Tests of
      independence are used (chi-square and Cramer's V-value tests) to find out the
      relationships between any two variables. In addition two- and three-dimensional
      log-linear models are used to obtain estimated parameters and expected
      frequencies for these models. Amongst the models fitted, the best are chosen
      based on the analysis of deviance. The results of this study show that most
      paired variables of personal, cancer/clinical variables are significantly related
      at p-value <0.05. For both male and female patients, the variable site of the
      cancer is highly related to marital status, diagnostic evidence and treatment,
      which provide the highest Cramer's V value. Moreover, the site of cancer also
      affects the method of diagnostic evidence and treatment. Since the site of cancer
      in each sex is different, prevention for various sites of cancer should be
      considered for each specific sex. In addition, for male and female patients,
      treatment is related to the site of cancer. Consequently, physicians may consider
      these factors before selecting the appropriate method of treatment.

PMID- 16438160
TI  - Von Willebrand factor (vWF) antigen levels and function in healthy Thais.
AB  - Type I von Willebrand disease (vWD) is very common in caucasians. Its genetic
      basis is possibly heterogenous, lying both within and out of the vWF gene locus.
      We sought to investigate vWF levels in the Thai population, to compare with those
      of western countries. The vWF antigen and activity were measured using ELISA and
      Collagen Binding Assay (CBA), respectively, in 311 healthy Thai volunteers. The
      mean age was 32.3, ranging from 18 to 75 years. Fifty-four percent were female.
      Low vWF antigen and activity (below 50 U/dl) were found in 3.5% and 10.2%,
      respectively. Around 75% and 20% of these cases had O and A blood groups,
      respectively. Three (0.96%) had definitely low levels of vWF (vWF antigen level
      below 35 U/dl), suggesting the diagnosis of vWD. Similar to previous studies, vWF
      levels were lowest in subjects with group O blood. We found that subjects with
      blood group A had higher vWF levels than group O subjects, but significantly
      lower vWF levels than those with group B. The average ratio between the vWF
      activity and antigen was 0.96, ranging from 0.66 to 1.66. These ratios were
      inversely correlated with age (p=0.047), suggesting a decline in vWF activity per
      vWF protein with advancing age. Low levels of vWF are common in healthy Thais.
      Clinicians should be aware of vWD in bleeding patients and beware low levels of
      vWF in therapeutic plasma products, especially from blood groups O and A.

PMID- 16438161
TI  - Enhanced maturation and proliferation of beta-thalassemia/Hb E erythroid
      precursor cells in culture.
AB  - Upon erythroid cell maturation in vivo, beta-thalassemic erythroid cells
      accumulate unmatched unstable alpha-globin chains that are believed to be a
      causal factor in such cell destruction. This study showed that beta
      thalassemia/Hb E erythroid precursor cells from peripheral blood had accelerated
      maturation, and could mature to the terminal erythroid stage. During the early
      period of cell culture, erythroid precursor cells derived from subjects with the
      more severe form of beta-thalassemia/Hb E had higher rate of erythroid
      maturation. In addition, peripheral blood mononuclear cells from beta
      thalassemia/Hb E subjects had higher erythroid proliferative potential than cells
      derived from normal controls. Erythroid proportion in the more severe beta
      thalassemia/Hb E cases was less than that of the milder cases. Premature
      apoptosis was not observed during the 15 days of erythroid cell culture from both
      beta-thalassemia/Hb E and normal subjects.

PMID- 16438162
TI  - Anemia and iron status of Malay women attending an antenatal clinic in Kubang
      Kerian, Kelantan, Malaysia.
AB  - The purpose of this study was to detect the frequency of iron deficiency anemia
      in women attending their first antenatal clinic at a Maternal and Child Health
      Clinic in Kubang Kerian, a district of Kelantan that is located on the East coast
      of Malaysia. A cross-sectional study was done over a two-month period and fifty
      two Malay women were enrolled in this study. Red blood cell indices and serum
      ferritin were used as a screening tool for anemia and iron status. Eighteen
      patients (34.6%) were anemic. The majority were classified as having mild anemia
      (90%). Four of them had hypochromic microcytic anemia. Of 52 women, 7 had iron
      deficient erythropoiesis and 11 (61.1%) had iron deficient anemia. The prevalence
      of iron deficiency anemia in pregnant women was 21.2%, which is similar to other
      developing countries. The serum ferritin level was significantly associated with
      the hemoglobin level (p=0.003). Other red blood cell indices were not useful in
      predicting iron deficient erythropoiesis. It is important to detect iron
      deficient erythropoiesis during the first antenatal check-up, as it is an early
      manifestation of iron deficiency anemia. In conclusion, screening for iron
      deficient is recommended during first antenatal visit because iron deficiency
      anemia is still the leading cause of nutritional deficiency in pregnant women.
      This will initiate an early therapeutic intervention so as to reduce public
      health problem.

PMID- 16438163
TI  - The molecular basis of mucopolysaccharidosis type I in two Thai patients.
AB  - Two Thai patients diagnosed with Hurler syndrome (mucopolysaccharidosis type 1,
      MPS I) were found to have no detectable alpha-iduronidase (E.C. 3.2.1.76)
      activity in leukocytes, while normal Thai children all had significant activity,
      with a mean of 135 +/- 30 nmol/mg/18h. One patient was heterozygous for A75T
      (311G>A) and S633L (1986C>T) mutation, previously reported to cause MPS I,
      together with 9 other heterozygous polymorphisms also found in normal controls.
      The other patient had the previously described frameshift mutation 252insert C
      and a new nonsense mutation E299X (983G>T).

PMID- 16438164
TI  - Predictors of relapse in steroid-sensitive nephrotic syndrome.
AB  - The objective of this study was to identify predictors of relapse and determine
      the predictive score for relapse in steroid-sensitive nephrotic syndrome. Ninety
      nine children with nephrotic syndrome visiting the pediatric nephrology
      outpatient clinic of Soetomo Hospital from 1983 to 2001 were studied. There were
      63 children with relapses (50 infrequent relapses, 13 frequent relapses) and 36
      children without a relapse for at least 1 year after beginning steroid treatment,
      which served as a control group. The selected variables were grouped into non
      renal factors (age, sex, nutritional status, infection) and renal factors
      (histopathologic findings, hypertension, hematuria, azotemia, hypocomplementemia,
      rapidity of early steroid response, number of relapses within the first 6 months,
      time-interval between early steroid response and first relapse). Using the
      discriminant analysis function test, it was found that the statistically
      significant predictors of relapse were the time-interval between early steroid
      response and the first relapse, number of relapses within the first 6 months,
      infection during the first relapse, hematuria and sex. A prediction score can be
      determined using 3, 5 or 6 parameters by including the rapidity of early steroid
      response.

PMID- 16438165
TI  - Prevalence of iodine deficiency disorders among schoolchildren in three blocks of
      Bardhaman District and Bardhaman Municipal area of West Bengal, India: a
      comparative study.
AB  - Urinary iodine levels in children (6-12 years) living in three rural blocks and
      in the municipal urban area of Bardhaman District, West Bengal, were analyzed to
      compare the status of recent iodine nutrition in the rural and urban population
      of the district. Goiter, indicating previous iodine status, was simultaneously
      estimated. Iodine levels in salt samples, that provide insight into the usage of
      iodized salt, were estimated. Data indicated that 56.6% of urban children and
      51.1% of rural children were biochemically iodine repleted and had urinary iodine
      excretion (UIE) levels > or = 10microg/dl. Urban children (29.4%) and rural
      children (37.1%) were found to have goiter. Eighty percent and 50% of the rural
      and urban salt samples, respectively, were found to have iodine levels below 10
      ppm; with significant urban-rural differences. The results indicate that iodine
      repletion in the surveyed area needs continuous surveillance of the proper
      distribution and use of iodized salt.

PMID- 16438166
TI  - A medico-social appraisal of commercial sex workers in a metropolitan city from
      eastern India.
AB  - This cross-sectional study of 146 commercial sex workers (CSWs) selected by
      stratified sampling, in a red light area of Kolkata, showed that 25.3% were
      teenagers and 37.0% were forced into the profession due to poverty. White
      discharge was present in 42.5% of the CSWs. Only 65.1% had the proper knowledge
      of the causes of disease, but 49.3% preferred to go to "quacks" for treatment,
      while 42.5% preferred traditional medicine. Knowledge of the prevention of
      sexually transmitted infections by condom use was correct in 44.2% of the CSWs,
      but 17.8% used condoms regularly. One fourth of the CSWs having 5 or more clients
      per day used condoms regularly.

PMID- 16438167
TI  - Changes in marriage age and first birth interval in Huaning County, Yunnan
      Province, PR China.
AB  - The timing of marriages, first birth interval and the prevalence of premarital
      conception (PMC) among women of successive birth cohorts in one rural county in
      Yunnan, China, were examined. Detailed pregnancy histories were collected for
      1,336 women aged 15-64 years using a Life History Calendar. The rising marriage
      age and shorter first birth interval correspond to over-all changes in the
      Chinese society over the same time period. The mean age at first marriage for
      women born before 1950 was just below 20, and 22.5 among women born 1976-1980.
      The later marriage age was partly offset by the dramatic shortening of the first
      birth interval from over 30 months in the oldest cohort to 11-12 months in the
      youngest. One explanation of the shortening of the first birth interval may be
      the increase in premarital conception. Among the young women in our study almost
      one-third of first pregnancies were conceived before marriage.

PMID- 16438168
TI  - Secular trends and contemporary differences in physique and health-related
      fitness levels of 11-12 year-old South Korean and New Zealand children.
AB  - Physique and physical fitness levels of 343 South Korean and 260 New Zealand 11
      12-year-old schoolchildren were measured between 2000 and 2001 and added to
      previous data to investigate secular trends and contemporary patterns in these
      health-related variables. Secular trend data suggest that South Korean children
      are growing taller at a faster rate but are also increasing in body mass faster
      than New Zealand children. Contemporary South Korean children had significantly
      higher sit and reach and broad jump scores compared to New Zealand children,
      however aerobic fitness was similar between the cohorts except for 11-year-old
      New Zealand girls who took significantly longer to complete the 550-m run.
      Contemporary South Korean and New Zealand children's physiques are similar at
      present but if current trends continue South Korean children will become more
      obese than their New Zealand counterparts. An increase in South Korean children's
      fat mass will also have a detrimental effect on their currently superior fitness
      levels and overall health.

PMID- 16438169
TI  - Perceptions of the prevalence of cigarette smoking by peers: a study of
      Taiwanese, Filipino, and Thai high school students.
AB  - Youth cigarette smoking is a major public health concern in Southeast Asia. A
      suspected determinant of youth smoking is perceived peer behavior. Previous
      research has suggested that the probability that a teenager will use substances
      increases when there is the perception that most peers engage in the substance
      use behavior. This study aimed to assess the perceptions of the prevalence of
      peer cigarette smoking in samples of high school students from three Southeast
      Asian countries and to examine the association of these perceptions to self
      reported personal use of cigarettes. Perceptions of the prevalence of peer
      smoking were generally characterized by the perception that most students do not
      smoke. However, a significant percentage of students held the perception that
      most students were current smokers. Students who held this perception were at
      increased risk of being current smokers relative to those who believed most
      students were not current smokers. The results of this study imply that public
      health programs may benefit from health promotion interventions which focus on
      dispelling misconceptions that most youth smoke cigarettes.

PMID- 16438170
TI  - Comparison of physiological, cytopathogenic and immunological properties between
      two environmental isolates of Acanthamoeba spp.
AB  - The aim of this study was to determine whether pathogenic and less-pathogenic
      isolates of environmental Acanthamoeba exhibit differences in adhesion to human
      erythrocytes. Based on physiological properties of temperature, tolerance, and
      rapid growth, Acanthamoeba were divided into pathogenic and less-pathogenic
      isolates. Acanthamoeba were tested for their ability to produce cytopathic
      effects (CPE) using two human cell lines, HEp-2 and KB cells. Both ameba isolates
      caused CPE to both cell lines with the same pattern without significant
      difference. Human erythrocytes from 20 healthy volunteers were used to study the
      erythrocyte reactivity of Acanthamoeba by co-incubation with trophozoites. The
      pathogenic Acanthamoeba exhibited significantly higher erythrocyte adhesion as
      compared to the less-pathogens (p<0.05). Erythrocyte activity occurred in the
      presence of plasma in all blood samples, suggesting the role of plasmatic
      components and contact-dependent mechanisms to produce host cell cytotoxicity.
      The present results showed correlation between the physiological properties and
      erythrocyte reactivity of Acanthamoeba.

PMID- 16438171
TI  - Free-living ameba contamination in natural hot springs in Thailand.
AB  - Thermo tolerant free-living ameba, Naegleria spp and Acanthamoeba spp
      contamination in natural hot springs in Thailand were carried out from 13
      provinces. The temperature of hot springs water varied from 28 degrees-65 degrees
      C and pH from 6-8. We found that 38.2 % (26/68) of water samples were positive,
      Acanthamoeba was 13.2% (9/68) whilst Naegleria was 35.3% (24/68). Contamination
      by free-living ameba in natural hot springs may pose a significant health risk to
      people who use such water for recreation activities.

PMID- 16438172
TI  - Spa, springs and safety.
AB  - Natural mineral water has long been used worldwide for bathing and health
      purposes. At present, Thailand is famous for health spas and natural hot springs
      among local people and tourists. Due to possible risks of exposure to harmful
      agents, we studied hazardous pollutants at 57 natural hot springs from 11
      provinces in northern, central, eastern and southern Thailand. Pathogenic, free
      living amebae of the genera Naegleria and Acanthamoeba, which can cause central
      nervous system infection, were found in 26.3% (15/57) and 15.8% (9/ 57),
      respectively. Dissolved radon, a soil gas with carcinogenic properties, was
      present in nearly all hot springs sites, with concentration ranging from 0.87
      76,527 Becquerels/m3. There were 5 water samples in which radon concentration
      exceeded the safety limit for drinking. Legionella pneumoniphila (serogroups 1,
      3, 5, 6, 7 10 and 13) were found in samples from 71.9% (41/57) of studied sites.
      Because spas and natural springs are popular tourist attractions, health
      authorities should be aware of possible hazards and provide tactful measures and
      guidelines to ensure safety without causing undue alarm to foreign and Thai
      tourists.

PMID- 16438173
TI  - Prevalence of Blastocystis hominis infection in asymptomatic individuals from
      Bangkok, Thailand.
AB  - Fresh stool examination was performed from 2,230 participants who enrolled in
      annual check-up programs of the Faculty of Medical Technology, Mahidol University
      in 1999-2000 and 2004. In this study, Blastocystis hominis infection was
      diagnosed by culturing in Jones' media. A total of 21% of fecal specimens (in
      1999-2000) and 13.7% (in 2004) were positive for B. hominis. The vacuolated form
      was the predominant form found in culture solution after 48 hours of incubation.
      The distribution of infection was highest between the ages of 21-30 years
      (p<0.05). There was no significant difference in infection between male and
      female groups. Other parasites, eg Giardia lamblia, Entamoeba histolytica,
      Entamoeba coli, Endolimax nana, Trichomonas hominis, Strongyloides stercoralis,
      Opisthorchis viverrini and Taenia species, were also found by fresh stool
      examination.

PMID- 16438174
TI  - Current infection rate of Giardia lamblia in two provinces of Thailand.
AB  - The aim of this study was to survey for the current rate of Giardia lamblia
      infection in three different districts in two provinces of Thailand, Surin and
      Samut Sakhon, in March 2002, October 2003, and March 2004. Two districts are
      rural areas and another is sub-urban. Volunteers of any age from Surin Province
      and children aged between 5 to 7 years old from three secondary schools in Samut
      Sakhon were enrolled for the stool examination. The method used was stool
      examination by both simple smear and normal saline concentration technique on
      fresh collected feces. All samples were tested in duplicate. Out of 3,358 healthy
      individuals from rural Surin Province, 75 cases (2.2%) were found positive for G.
      lamblia, 30 of which were below 10 years of age. By comparison, 656 individuals
      from sub-urban Samut Sakhon Province volunteered and 43 (6.5%) were positive for
      G. lamblia. Other intestinal parasites, both helminth and protozoa, were also
      identified from these two groups: hookworm, Enterobius vermicularis,
      Strongyloides stercoralis, Trichuris trichiura, Taenia species, Entamoeba
      histolytica, Entamoeba coli, Endolimax nana, and Blastocystis hominis. From this
      study, the data showed that parasitic infection acquired via fecal-oral route is
      still a significant problem for these two provinces of Thailand.

PMID- 16438176
TI  - Prevalence of cryptosporidiosis in HIV-infected patients in Kajang Hospital,
      Selangor.
AB  - A total of 66 fecal specimens obtained from patients infected with human
      immunodeficiency virus (HIV) from Kajang Hospital were screened for
      Cryptosporidium oocysts. The fecal specimens were concentrated using the formalin
      ethyl acetate concentration technique, stained with modified Ziehl-Neelsen and
      confirmed with immunofluorescence stain. It was established that 2 (3.0%) were
      positive for Cryptosporidium. The two cases involved a Chinese local man (with
      diarrhea) and an Indonesian foreigner (without diarrhea). A higher index of
      suspicion for clinical cryptosporidiosis in HIV patients, including those with
      chronic weight loss with or without diarrhea, is recommended. In addition,
      laboratory testing for Cryptosporidium in HIV-infected patients is highly
      recommended in order to have a better understanding of the epidemiology and
      management of the disease in Malaysia.

PMID- 16438177
TI  - Occurrence of Cryptosporidium oocysts in Wrinkled Hornbill and other birds in the
      Kuala Lumpur National Zoo.
AB  - The occurrence of a coccidian parasite, Cryptosporidium, among birds in the Kuala
      Lumpur National Zoo was investigated in this study. A hundred bird fecal samples
      were taken from various locations of the zoo. Fecal smears prepared using direct
      smear and formalin ethyl acetate concentration technique were stained with
      modified Ziehl-Neelsen stain. Samples positive for Cryptosporidium with Ziehl
      Neelsen stain were later confirmed using the immunofluorescence technique and
      viewed under the epifluorescence microscope. Six species of bird feces were
      confirmed positive with Cryptosporidium oocysts. They included Wrinkled Hornbill
      (Aceros corrugatus), Great Argus Pheasant (Argusianus argus), Black Swan (Cygnus
      atratus), Swan Goose (Anser cygnoides), Marabou Stork (Leptoptilos crumeniferus),
      and Moluccan Cockatoo (Cacatua moluccencis). These birds were located in the
      aviary and lake, with the Moluccan Cockatoo routinely used as a show bird.
      Results obtained in this study indicated that animal sanctuaries like zoos and
      bird parks are important sources of Cryptosporidium infection to humans,
      especially children and other animals.

PMID- 16438175
TI  - Re-evaluation of commercially available enzyme-linked immunosorbent assay for the
      detection of Giardia lamblia and Cryptosporidium spp from stool specimens.
AB  - This study aimed to detect Giardia lamblia and Cryptosporidium spp infection from
      stool specimens. A total of 345 stool specimens were examined by microscopy (both
      direct smear and formalin concentration) and EIA techniques (ProSpecT Microplate
      Assay) for G. lamblia and Cryptosporidium spp. Of 73 tests positive for G.
      lamblia, 41(56.2%) were positive by microscopy, and 71(97.3%) were positive by
      EIA. Of 16 tests positive for Cryptosporidium spp, 5 (31.3%) were positive by
      microscopy, and 16(100%) were positive by EIA technique. The results demonstrate
      that this EIA method is quick, simple, and more sensitive than the microscopy
      method and should be used for the detection of G. lamblia and Cryptosporidium spp
      where the prevalence of these protozoan parasites is a public health problem.

PMID- 16438178
TI  - Protozoal contamination of water used in Thai frozen food industry.
AB  - This study evaluated the prevalence of contamination of water that was used for
      food preparation. Since protozoal cysts can be found in small numbers in water,
      1,000 liters of either untreated or treated water were filtered through activated
      carbon block filters (1 microm nominal porosity). Identification of protozoa was
      performed using specific monoclonal antibodies against Giardia and
      Cryptosporidium parasites followed by fluorescence microscopy. Twelve of 20
      untreated water samples (60%) were found to be contaminated by Giardia cysts,
      with an average of 53.33 cysts/1,000 liters (geometric mean 39.43), whilst 7
      samples (35%) were contaminated by Cryptosporidium oocysts, with an average of
      28.57 oocysts/1,000 liters (geometric mean 26.92). Three samples of untreated
      water (15%) were positive for both organisms. In contrast, none of the treated
      water samples were contaminated.

PMID- 16438179
TI  - Serologic detection of Toxoplasma gondii infection in Rattus spp collected from
      three different sites in Dasmarinas, Cavite, Philippines.
AB  - Acute and chronic cases of toxoplasmosis in Rattus norvegicus and Rattus rattus
      mindanensis caught in agricultural, commercial and residential sites in
      Dasmarinas, Cavite, Philippines were determined serologically. Fifty-eight
      percent of R. norvegicus and 42.0% of R. r. mindanensis were positive for anti-T.
      gondii antibodies (Abs). Infection was higher in male rats, and those caught in
      the commercial site had 100.0% seropositivity. Thirty percent of the R.
      norvegicus and 51.0% R. rattus mindanensis had acute infection, with 1:64-1:128
      Abs titer. Seventy percent of the R. norvegicus and 49.0% of R. rattus
      mindanensis were chronically-infected with Abs titer 1:256-1:2048 and 1:256-1024,
      respectively. The association between the presence of infection with the rat
      gender and species and their collection sites was insignificant (p>0.05). In a
      related study, however, mice experimentally-inoculated brain tissue homogenate
      obtained from chronically-infected Rattus spp, manifested differences in the
      onset as well as, severity of infection which was histopathologically evaluated,
      suggestive of a possible difference in T. gondii parasite strain(s) infecting
      different rat populations.

PMID- 16438180
TI  - Parasitic infections in Malaysia: changing and challenges.
AB  - A total of 1,885 blood and stool samples of four main protozoan parasitic
      infections were retrospectively reviewed from January, 2000 to April, 2004.
      Eleven of the 1,350 stool samples were shown positive for Cryptosporidium and
      Giardia infections; one of the 5 cases was clinically diagnosed as
      gastrointestinal cryptosporidiosis, while 6 cases were giardiasis. In patients
      with giardiasis, children were among the high-risk groups, making up 66.7% of
      these patients. The common presenting signs and symptoms were: diarrhea (83.3%),
      loss of appetite (83.3%), lethargy (83.3%), fever (66.7%), nausea/vomiting
      (50.0%), abdominal pain (16.7%), dehydration (16.7%) and rigor and chills
      (16.7%). Metronidazole was the drug of choice and was given to all symptomatic
      patients (83.3%). For the blood samples, 28 of the 92 peripheral smears for
      Plasmodium spp infection were diagnosed as malaria. The age range was from 4 to
      57, with a median of 32.5 years. The sex ratio (M:F) was 3.6:1, while the age
      group of 30-44 years was the most commonly affected in both sexes. The majority
      of patients were foreigners (60.7%) and non-professional (39%). Plasmodium vivax
      (71%) infection was the most common pathogen found in these patients, along with
      a history of traveling to an endemic area of malaria (31%). The predominant
      presenting signs and symptoms were: fever (27%), rigor and chills (24%),
      nausea/vomiting (15%) and headache (8%). Chloroquine and primaquine was the most
      common anti-malarial regimen used (78.6%) in these patients. The seroprevalence
      of toxoplasmosis in different groups was 258/443 (58%): seropositive for IgG 143
      (32.3%); IgM 67 (15%); and IgG + IgM 48 (10.8%). The age range was from 1 to 85,
      with a mean of 34 (+/- SD 16.6) years. The predominant age group was 21 to 40
      years (126; 28.4%). The sex ratio (M:F) was 1.2:1. Subjects were predominantly
      male (142; 32%) and the Malay (117; 26.4%). Of these, 32 cases were clinically
      diagnosed with ocular toxoplasmosis. The range of age was from 10 to 56 years
      with a mean of 30.5 (+/- SD 12.05) years. The sex ratio (M:F) was 1:1.7. The
      majority were in the age group of 21 to 40 years, female (20; 62.5%), and Malay
      (17; 53%). They were also single (16; 50%), unemployed (12; 37%), and resided
      outside Kuala Lumpur (21; 65.6%). The more common clinical presentations were
      blurring of vision (25; 78%), floaters (10; 31%) and pain in the eye (7; 22%). We
      found that funduscopic examination (100%) and seropositivity for anti-Toxoplasma
      antibodies (93.7%) were the main reasons for investigation. Choroidoretinitis was
      the most common clinical diagnosis (69%), while clindamycin was the most
      frequently used antimicrobial in all cases. Among HIV-infected patients, 10 cases
      were diagnosed as AIDS-related toxoplasmic encephalitis (TE) (9 were active and 1
      had relapse TE). In addition, 1 case was confirmed as congenital toxoplasmosis.

PMID- 16438181
TI  - Malaria: a 10-year (1994-2003) retrospective study at University Malaya Medical
      Center (UMMC), Kuala Lumpur, Malaysia.
AB  - Malaria is still one of the most important vector-borne diseases in Malaysia,
      particularly in remote areas. This retrospective study was carried out to find
      the prevalence of malaria among patients admitted to UMMC Kuala Lumpur, from 1994
      2003. A total of 86 malaria cases were analyzed. Most cases occurred among
      foreigners [57% (49 cases)] while Malaysians constituted 43% (37 cases). Among
      foreigners, Indonesians constituted the most [57% (28 cases)]. Among Malaysians,
      most cases occurred among the Chinese [35% (13 cases)] followed by the Malays
      [30% (11 cases)]. Males [70%(60 cases)] were more commonly affected. The majority
      of cases were within the 20-39 year age group (69%). Three species of malaria
      parasites were reported, of which Plasmodium vivax constituted the most [55%( 47
      cases)], followed by Plasmodium falciparum [29% (25 cases)], and only four cases
      (5%) of Plasmodium malariae. Nine percent (8 cases) were mixed infections. In
      this study, 12%(10 cases) developed chloroquine resistance: 7 cases of P.
      falciparum, and 3 cases of P. vivax. The most common complications were jaundice
      and anemia [77% (23 cases)], followed by blackwater fever [13% (4 cases)] and
      cerebral malaria [10% (3 cases)]. Most of the complications were due to P.
      falciparum [43% (13 cases)]. There were no reported deaths. This new source of
      malaria coming from foreigners must be given serious attention, as it has great
      potential of increasing malaria cases in urban Malaysia.

PMID- 16438182
TI  - Chronicle of malaria epidemics in Thailand, 1980-2000.
AB  - The occurrence of malaria epidemics in Thailand was reviewed from the malaria
      surveillance report of the National Malaria Control Program. The literature
      review revealed that the four epidemic periods recorded during 1980-2000 almost
      always occurred in the provinces and districts located along international
      borders. Malaria epidemics are caused by various factors such as: extensive
      population movement, multi-drug resistance development, low immune status of the
      population, lack of knowledge and appropriate personal protection against
      mosquito biting, and the re-emergence of malaria transmission in low malarious
      areas. Such factors can lead to changes in the parasite ratio and appearance of
      malaria epidemics throughout the country. Evidence related to the burden of
      malaria epidemics was also reviewed to identify causal factors that will be
      helpful in future research.

PMID- 16438183
TI  - Malaria: the value of the automated depolarization analysis.
AB  - This retrospective and descriptive study was carried out in the University of
      Malaya Medical Center (UMMC) from January to September, 2004. This study aimed to
      evaluate the diagnostic utility of the Cell-Dyn 4000 hematology analyzer's
      depolarization analysis and to determine the sensitivity and specificity of this
      technique in the context of malaria diagnosis. A total of 889 cases presenting
      with pyrexia of unknown origin or clinically suspected of malaria were examined.
      Sixteen of these blood samples were found to be positive; 12 for P. vivax, 3 for
      P. malariae, and 1 for P. falciparum by peripheral blood smear as the standard
      technique for parasite detection and species identification. Demographic
      characteristics showed that the majority of patients were in the age range of 20
      57 with a mean of 35.9 (+/- SD) 11.4 years, and male foreign workers. Of these,
      16 positive blood samples were also processed by Cell-Dyne 4000 analyzer in the
      normal complete blood count (CBC) operational mode. Malaria parasites produce
      hemozoin, which depolarizes light and this allows the automated detection of
      malaria during routine complete blood count analysis with the Abbot Cell-Dyn
      CD4000 instrument. The white blood cell (WBC) differential plots of all malaria
      positive samples showed abnormal depolarization events in the NEU-EOS and EOS I
      plots. This was not seen in the negative samples. In 12 patients with P. vivax
      infection, a cluster pattern in the Neu-EOS and EOS I plots was observed, and
      appeared color-coded green or black. In 3 patients with P. malariae infection,
      few random depolarization events in the NEU-EOS and EOS I plots were seen, and
      appeared color-coded green, black or blue. While in the patient with P.
      falciparum infection, the sample was color-coded green with a few random purple
      depolarizing events in the NEU-EOS and EOS I plots. This study confirms that
      automated depolarization analysis is a highly sensitive and specific method to
      diagnose whether or not a patient has malaria. This automated approach may prove
      to be particularly useful in situations where there is little or no clinical
      suspicion of malaria.

PMID- 16438184
TI  - In vitro susceptibility and genetic variations for chloroquine and mefloquine in
      Plasmodium falciparum isolates from Thai-Myanmar border.
AB  - In vitro drug susceptibility to chloroquine (CQ) and mefloquine (MF) were
      assessed in 39 P. falciparum isolates from the Thai-Myanmar border area. To
      further characterize CQ- and MF-resistance profiles in this area, we also
      analyzed pfcrt K76T mutation that is critical for CQ resistance, and pfmdr1
      polymorphism that has an association with MF resistance. Eighteen isolates were
      successfully examined by in vitro tests for CQ, and 17 of them had resistance to
      the drug. Geometric mean concentration of CQ that inhibited the growth of
      parasites at 50% (IC50) was 371 +/- 227 nM (105-971 nM). Sixteen isolates were
      successfully examined by in vitro tests for MF, and 8 of them were resistant to
      the drug. Geometric mean of IC50 for MF was 41 +/- 31 nM (4-125 nM). Genotypes of
      drug resistance, such as pfcrt and pfmdr1 mutations, were also analyzed. All the
      39 isolates had the same haplotype (CVIET) for PfCRT at its 72-76th amino acids.
      A pfmdr1 Y86 mutation was found in 95% of isolates. A pfmdr1 D1042 mutation was
      also present in 7 isolates, while no pfmdr1 Y1246 mutation was observed. These
      results indicated a correlation between CQ resistance and the pfcrt T76 and
      pfmdr1 Y86 mutations.

PMID- 16438185
TI  - Detection of IgG antibodies of Brugian filariasis with crude male and female
      antigens of Dirofilaria immitis.
AB  - Crude antigens from male and female Dirofilaria immitis were used to detect
      antibody to Brugian filariasis in humans by indirect ELISA. Both antigens were
      tested with 42 cases of Brugian filariasis, 131 cases of 20 heterologous
      infections and 35 healthy controls. The results--using male and female antigens-
      showed sensitivity of 88.1% and 88.1%, and specificities of 64.1% and 51.8%,
      respectively. Cross-reaction from other helminthic infections using crude male
      antigen gave false-positives with 48 sera from 13 heterologous diseases at the
      threshold value of 0.180, while the female antigen gave 63 sera from 15 diseases,
      at 0.309. Serum antibodies from patients with other helminthic infections-
      gnathostomiasis, strongyloidiasis, hookworm infections, trichinellosis,
      capillariasis, angiostrongyliasis, ascariasis, trichuriasis, toxocariasis,
      neurocysticercosis, cystic echinococcosis, taeniasis and opisthorchiasis-
      resulted in false-positives with both male and female antigens. One each of
      sparganosis and paragonimiasis heterotremus sera cross-reacted with only crude
      female antigen and their OD values were close to the threshold value. Although
      crude male antigen showed better specificity than crude female antigen, both
      female and male worms are sources of antigens needed for further purification.
      This study provides baseline data for further serodiagnosis of Brugian filariasis
      using dirofilaria antigen.

PMID- 16438186
TI  - A preliminary study on in vitro transmission of Dirofilaria immitis infective
      stage larvae by Aedes aegypti (L.) (Diptera: Culicidae).
AB  - This study was performed to study an in vitro transmission of infective stage
      larvae from the mosquito proboscis. There were five experiments with 949
      mosquitoes. Liverpool strain of Aedes aegypti (L.) were used in this study. They
      were allowed to feed on D. immitis infected dogs with different microfilarial
      levels which were 1,650, 1,950, 9,000, 9,250, and 11,550 microfilariae per one ml
      of blood. Mosquitoes were forced to feed on solution (5% sucrose in 5% dog serum)
      in capillary tubes for 20 minutes at 7-34 days post-blood feeding. Solutions in
      capillary tubes then were examined and mosquitoes were dissected and examined for
      D. immitis larvae under a light microscope. Second stage larvae could be found in
      the abdomen and malpighian tubules of mosquitoes and third stage larvae can be
      found in the abdomen, malpighian tubules, thorax, and proboscis of mosquitoes
      with different levels of infection. No larvae were detected in the solution in
      capillary tubes of all experiments.

PMID- 16438187
TI  - Feasibility of using papaya skin extract for digestion of swamp eel viscera for
      harvesting infective stage larva of Gnathostoma spp.
AB  - In this study, we reported the feasibility of using papaya skin extract (Carica
      papaya L.) as an alternative to enzyme pepsin in harvesting Gnathostoma
      spinigerum third-stage larvae. From experimental digestion, we found that the
      different numbers of recovered larvae between papaya skin extract and pepsin were
      not statistically significant (p >0.05). When the derived larvae from pepsin and
      papaya skin extract digestion were cultivated in BME medium for 7 days, the
      survival rates were not significantly different either (p >0.05). Thus, papaya
      skin extract might be another choice for recovering Gnathostoma spinigerum third
      stage larvae.

PMID- 16438188
TI  - Host-finding behavior of Strongyloides stercoralis infective larvae to sodium
      cation, human serum, and sweat.
AB  - The host-finding behavior of Strongyloides stercoralis infective larvae was
      examined by in vitro agarose assay method. As human body fluid contains 0.85% (ca
      0.15 molar) NaCl, various concentrations of sodium chloride, from 0.5M to 0.01M
      (7 steps), were examined. Many larvae were attracted at concentrations between
      0.5 and 0.05M of sodium chloride. The concentration of 0.05M attracted the most
      larvae. The concentration of 0.02M of sodium chloride showed greatly reduced
      larval attraction compared with 0.05M. Therefore, the threshold concentration was
      determined as 0.05M. Then, 0.05M of chemicals were examined in a further
      experiment. Chloride compounds (NaCl, KCl, CaCl2, MgCl2) were investigated. These
      chemicals are components of human body fluids. Distilled water was used as the
      control in all experiments. Only sodium chloride attracted the larvae. Next,
      alkaline compounds were examined [NaOH, KOH, Ca(OH)2, and Mg(OH)2]. Larvae
      accumulated only at the NaOH site. The results suggested that the Na cation is
      important for larval attraction. A high pH value did not influence attraction at
      all. Next, human serum was tested. The human serum used was from normal serum to
      1:32 diluted sera by distilled water (7 steps). Hierarchical attraction was seen
      according to serum concentration. Next, human sweat was collected from a limited
      zone of chest skin where only eccrine glands were distributed. Non-diluted sweat
      attracted the most larvae. Sweat might act as one of the most probable factors
      for infection by this skin-penetrating nematode.

PMID- 16438189
TI  - Diploscapter coronata infection in Thailand: report of the first case.
AB  - A 73-year-old Thai woman living in Mueang District, Saraburi Province, central
      Thailand presented with numerous hookworm-like nematodes, finally revealed as
      Diploscapter coronata, by fecal culture. The patient exhibited no significant
      clinical signs of the gastrointestinal or genitourinary systems, and was
      generally not ill as a result of this unusual infection. Less commonly, patients
      have presented with symptoms and signs of Diploscapter coronata infection.
      However, potentially serious consequences can occur where people have exposure to
      an environment that has been contaminated with infected feces, or more
      specifically, infective eggs; such conditions could lead to human infection with
      Diploscapter coronata worms. This was the first reported occurrence of human
      Diploscapter coronata infection in Thailand.

PMID- 16438190
TI  - Molecular discrimination between individual metacercariae of Paragonimus
      heterotremus and P. westermani occurring in Thailand.
AB  - To accurately discriminate between individual metacercariae of Paragonimus
      heterotremus and P. westermani occurring in Thailand, polymerase chain reaction
      (PCR)-based molecular methods were established and subjected to an evaluation. We
      first amplified and sequenced the second internal transcribed spacer (ITS2)
      region of the nuclear ribosomal DNA of the two species. Based on their nucleotide
      differences, P. heterotremus and P. westermani were unequivocally discriminated
      from each other. These nucleotide differences were further utilized to select the
      ApaL1 endonuclease site for PCR-restriction fragment length polymorphism (PCR
      RFLP) analyses and to design species-specific primers for multiplex PCR
      reactions. Both PCR-RFLP and multiplex PCR methods allowed a more rapid and labor
      effective species discrimination. Furthermore, the multiplex PCR method enabled
      the most efficient discrimination because species identification involved a
      single round of PCR in a single tube. In Thailand, P. heterotremus is the only
      species affecting humans. Thus, the methods established in the present study can
      be used as reliable tools to identify the lung fluke metacercariae that cause
      human disease.

PMID- 16438191
TI  - Methylene blue staining method for identification of Opisthorchis viverrini egg.
AB  - Methylene blue staining method was used to distinguish O. viverrini eggs from
      Haplorchis taichui and Prosthodendrium molenkampi eggs. All eggs were obtained
      from dissected adult worms, fixed in 10% formalin, and stained with methylene
      blue prior to light microscopy observation. The distinct musk-melon-like texture
      of the O. viverini eggshell surface and the thread-like texture of H. taichui
      eggshell surface were recognized, while P. molenkampi eggs showed a smooth
      eggshell. We also evaluated the sensitivity and specificity of the method by
      training investigators to differentiate surface textures. After training, the
      investigators were randomly tested with 10 slides containing fluke eggs. The
      sensitivity and specificity were 95% and 95%, respectively.

PMID- 16438192
TI  - Survival of Haplorchis taichui metacercariae in Lab-Pla, Thai traditional food
      preparation.
AB  - Lab-Pla is a famous kind of Thai traditional food in northern and northeasthern
      Thailand. Consumption of uncooked Lab-Pla can lead to trematode infection because
      cyprinoid fish serve as the 2nd intermediate hosts of trematodes. The preparation
      of Lab-Pla can be made in different ways, depending on seasonings used in
      different places. The effect of the seasonings used in Lab-Pla on the survival of
      Haplorchis taichui metacercariae were, therefore, determined. The methodology was
      done by the following: 100 g of chopped Siamese mud carp fish (Henicorhynchus
      siamensis) were used for each experiment of seasonings used for completely mixed
      Lab-Pla. Mixed materials were blended and digested by 1% pepsin solution to
      obtain metacercariae and then checked for the movement under a stereomicroscope.
      The results showed that metacercariae remained active in 5 experimental groups:
      fermented fish treated, fish sauce treated, chili powder treated, ground roasted
      rice treated, and complete mixed treated indicated by average as follows: 27,
      38.7, 33.3, 42.7 and 21%, respectively. In conclusion, fermented fish and
      completely mixed methods have more effectiveness in killing metacercariae in Lab
      Pla preparation than other seasonings (p < 0.05).

PMID- 16438193
TI  - In vitro effects of aqueous extract from Artocarpus takoocha Roxb on tegumental
      surface of Haplorchis taichui.
AB  - The tegumental surface of the adult intestinal fluke, Haplorchis taichui, after
      in vitro incubation in Tyrode's solution containing 25, 50, 75 and 100% of
      aqueous extract of Artocarpus takoocha for 1, 6, 12 and 24 hours, was monitored
      by Scanning Electron Microscopy (SEM). The effect on worm motility was studied in
      contemporizing period. The adult worms stopped their motility immediately after
      being incubated with 25, 50, 75 and 100% of aqueous extract of A. takoocha.
      Observed under a light microscope, most worms showed bubbling from the oral
      sucker, ventral sucker and excretory pore. After exposure to the solution, SEM
      observation showed large blebs protruding from the oral sucker, ventral sucker
      and excretory pore. The surface damage was composed of numerous small blebs,
      followed later by the disruption of tegument. The severity of damage increased
      due to the increasing of aqueous extract of A. takoocha and incubation periods.

PMID- 16438194
TI  - Some factors affecting Stellantchasmus falcatus metacercaria in laboratory.
AB  - Killing factors, various temperatures and solutions were studied in the
      laboratory on Stellantchasmus falcatus metacercaria in half-beaked fish
      (Dermogenus pusillus). Killing criteria followed the Movability Index from 1.000
      within 24 hours. The metacercariae were collected from Chiang Mai moat. They were
      incubated in 0.85 % NaCl at -20 degrees C, room temperature, 4 degrees, 37
      degrees, and 65 degrees C. The in vitro investigation showed that at -20 degrees
      C and 65 degrees C, the worms were killed within 18 and 2 hours, respectively,
      while other temperatures produced no effect. The solutions investigated were NaCl
      (10, 20, 30, and 40%), lemon juice (25, 50, 75, and 100%), acetic acid (5, 10,
      20, and 30%), vinegar (1, 3, and 5%) and water as a control. The worms were
      killed in NaCl at 20, 30, and 40% within 12, 6, and 2 hours, respectively. Acetic
      acid at 5% and 10% killed the metacercaria within 12 and 6 hours while at 20% and
      30%, within 2 hours. The killing effect of 3% vinegar was found within 18 hours
      and of 5% vinegar within 12 hours. Lemon juice showed no killing effect.

PMID- 16438195
TI  - The correlation between rainfall and the prevalence of trematode metacercaria in
      freshwater fish in Thailand.
AB  - The author performed a retrospective study on 5 complete reports with
      geographical data and the prevalence of metacercariae in Thailand. The relation
      between rainfall (derived from the geographical data) and the prevalence of
      metacercariae in freshwater fish (derived from the overall infection rate of
      metacercaria) was investigated. The least- square equation plot rainfall (y)
      versus prevalence (x) is y = 12.4x + 43.8 (r = 0.858; p < 0.05). A significant
      correlation was discerned between rainfall and the prevalence of freshwater fish
      infection. According to these previous studies, the prevalence of freshwater fish
      infection may depend on rainfall. Predicted prevalence of freshwater fish
      infection as a GIS figure was also presented.

PMID- 16438196
TI  - Taeniasis and cysticercosis in Asia and the Pacific: present state of knowledge
      and perspectives.
AB  - Several topics on taeniasis and cysticercosis in Asia and the Pacific are
      overviewed. In Asia and the Pacific, three human taeniid species have been
      recognized: Taenia solium, Taenia saginata and Taenia asiatica. The first topic
      is on evolution of T. solium. Mitochondrial DNA polymorphisms of T. solium
      worldwide are discussed with emphasis of two specific genotypes: American-African
      and Asian. The second topic is recent major advances in sero- and molecular
      diagnosis of T. solium cysticercosis in humans, pigs and dogs. The third is the
      present situation of T. solium taeniasis/cysticercosis in Papua (Irian Jaya),
      Indonesia. The forth is the present situation of T. solium cysticercosis and T.
      saginata taeniasis in Bali, Indonesia. The fifth is the present situation of T.
      asiatica taeniasis in Asia and the Pacific and in North Sumatra, Indonesia. The
      sixth is on the debate of the exact definition of T. asiatica. Because T.
      asiatica can not be differentiated from T. saginata morphologically, it is time
      to re-evaluate T. saginata in Asia and the Pacific. New and broad-based surveys
      across this region are necessary from epidemiological and public health
      perspectives, based on evidence.

PMID- 16438197
TI  - Molecular identification of Taenia solium cysticercus genotype in the
      histopathological specimens.
AB  - PCR-based molecular diagnosis was done for identification of causative agents
      found in paraffin-embedded specimens that were resected from two suspected
      neurocysticercosis patients. DNA samples were extracted from tissues or sections
      and cytochrome c oxidase subunit 1 gene and cytochrome b gene were amplified for
      the detection of taeniid DNA. Two different genes were successfully amplified in
      both specimens, but the sizes of amplified products seemed to depend on the
      quality of DNA. Based on the nucleotide sequences of the PCR-amplified genes, the
      causative agents from two cases were identified as T. solium Asian genotype. When
      infection with T. solium is not confirmed by histopathological examination,
      molecular diagnosis will be more useful for definitive diagnosis.

PMID- 16438198
TI  - Fundamental study of expression-library immunization against Taenia taeniaeformis
      in rats.
AB  - Expression-library immunization has been proposed as an effective means to screen
      a large number of genes of the pathogen as candidate protective molecules. In
      this study, we examined the efficacy of expression-library immunization using a
      T. taeniaeformis rat model system. Total RNAs were isolated from the last 15
      segments of adult T. taeniaeformis and poly A RNA was purified. cDNA library was
      produced using SuperScript Plasmid System, which contains a mammalian expression
      vector, pCMV*SPORT6. From about 3,500 clones examined, more than 800 clones were
      found to contain DNA fragments. About 200 clones were sequenced and the homology
      search was carried out. The blast search revealed that 29% of the expression
      genes were mitochondrial genes (rRNA; 17%, protein; 12%). Nuclear rRNA genes
      (10%), nuclear protein (9%) and genes from Escherichia coli were also detected.
      Forty-two percent of sequences did not show a significant similarity to any genes
      deposited in the public database. Rats were immunized with expression-library and
      injected orally with 1,000 T. taeniaeformis eggs. However the protective effect
      of expression-library vaccine was not confirmed.

PMID- 16438199
TI  - Negative-ELISA using native and filtrated cystic fluid antigens to rule out
      cystic echinococcosis.
AB  - An increasing number of cases of echinococcosis in Thailand have been imported,
      probably native infections and medical transfers. Serodiagnosis is one diagnostic
      choice for interpreting infections before a further step is done. Due to limited
      antigen, indirect ELISA has been used as a negative screening test for IgG
      detection to rule out echinococcosis. Native hydatid cystic fluid (HCF) antigen
      from Belgium was used for such testing, in which the ODs-ELISA of samples were
      compared with those of two positive controls. Subsequently, hydatid cyst fluid
      from a Thai patient was obtained and the filtrated cyst fluid antigen [(<30)
      (>10) kDa, HCF30.10] was prepared to develop negative screening results for the
      serum samples. By using HCF, three of twenty-four samples resulted in higher ODs
      ELISA than the controls. In an attempt to observe the cross-reactivity of this
      native antigen, IgG-antibodies from many helminthiases cross-reacted and showed
      high ODs-ELISA. The HCF30.10 Ag was used to develop the test and analyze IgG
      antibodies from 5 positive controls (2 parasite-confirmed and 3 positive
      serodiagnosed), 183 heterologous cases of 29 diseases and 50 healthy control
      sera. At a cut-off value of 0.484, the test had 100% sensitivity and 42%
      specificity. Only Malayan filariasis, onchocercosis, fascioliasis, amebiasis,
      giardiasis and blastocystosis gave true negatives. Antibodies from nematodiases
      strongly cross-reacted with HCF30.10 Ag. Nine of fifty (18%) healthy serum
      controls produced higher OD-values than the cut-off. The routine ELISA uses the
      HCF30.10 Ag to produce a negative result to echinococcosis, because limited
      cystic fluid antigen (Thai patient) for test improvement, a lot of cross
      reactions and only two protoscolex-positive controls are available.

PMID- 16438200
TI  - Parasite biodiversity in Rattus spp caught in wet markets.
AB  - Rattus spp trapped in wet markets in Quiapo, Manila and Balayan, Batangas had
      ectoparasites, Echinolaelaps echidnius (mite), and Polyplax spinulosa (louse).
      The endoparasites identified were Hymenolepis diminuta; the acanthocephalan
      Moniliformis moniliformis; Taenia taeniaeformis strobilocercus larvae and
      Capillaria hepatica in liver; Trichosomoides crassicauda of the urinary bladder;
      Sarcocystis sp of muscle tissue; and two different species of stronglyloid
      looking intestinal nematodes. Rats had 100% infection with C. hepatica and T.
      taeniaeformis, exhibiting high parasitemia. The co-existence of rats with diverse
      parasitic species is reflective of the host's capability to support parasites'
      behavioral, physiological, and developmental needs. Despite heavy infection with
      intestinal parasites, and marked hepatic tissue damage owing to severe
      capillariasis and strobilocercus larval infection, all rats appeared healthy and
      agile, suggestive of a well-established rat host-parasite relationship. In view
      of the diversity and zoonotic nature of rat parasites, and the impoverished
      conditions prevailing in communities where Rattus spp survive and proliferate,
      they can readily facilitate parasite transmission to humans and other susceptible
      animal hosts.

PMID- 16438201
TI  - A study of ectoparasites of Canis lupus familiaris in Mueang district, Khon Kaen,
      Thailand.
AB  - We studied ectoparasites found on Canis lupus familiaris sampled in five areas in
      Mueang district, Khon Kaen Province, Thailand. The prevalence of fleas and ticks
      as well as their density were determined in 100 dogs that did not receive
      treatments. A total number of 458 ectoparasites was found corresponding to two
      species: 25.8% Ctenocephalides canis and 74.2% Rhipicephalus sanguineus. R.
      sanguineus was the most abundant species, and Ct. canis was the only flea species
      found. The stages of R. sanguineus were larvae (5.3%), nymphs (29.1%) and adults
      (39.1% in male and 26.5% in female). The stages of Ct. canis were larvae (41.5%)
      and adults (58.5%). Both species were commonly found on domestic dogs in all
      areas of the study. Ct. canis was not present on domestic dogs in one sub
      district. The prevalence rates of tick-harboring domestic dogs was 80% (R.
      sanguineus), and flea-haboring domestic dogs was 26% (Ct. canis).

PMID- 16438202
TI  - Evidence of anopheline mosquito resistance to agrochemicals in northern Thailand.
AB  - The objective of this study was to assess insecticide resistance in anopheline
      mosquito populations in agroecosystems with high and low insecticide use in a
      malaria endemic area in Chiang Mai province in northern Thailand. Anopheline
      mosquitoes were collected in May and June 2004 from two locations with different
      agricultural insecticide intensity (HIGH and LOW), but similar in vector control
      strategies. The F1-generation of Anopheles maculatus s.s. and An. sawadwongporni
      were subjected to diagnostic doses of methyl parathion (MeP) and cypermethrin
      (Cyp), both commonly used insecticides in fruit orchards in Thailand. An. minimus
      A from the HIGH location was subjected to diagnostic doses to Cyp. CDC bottle
      bioassays were used to determine insecticide susceptibility. Time-mortality data
      were subjected to Probit analyses to estimate lethal time values (LT50 and LT90).
      Lethal time ratios (LTR) were computed to determine differences in lethal time
      response between populations from HIGH and LOW locations. The mortality of An.
      maculatus to MeP was 74% and 92% in the HIGH and LOW locations, respectively. The
      corresponding figures for An. sawadwongporni were 94% and 99%. There was no
      indication of resistance to Cyp for all species tested in either location. The
      LT90 and LT50 values of An. maculatus s.s. subjected to diagnostic doses of MeP
      were significantly different between locations (p<0.05). Reduced susceptibility
      to MeP in mosquito populations in the HIGH location is caused by intensive
      agricultural pest control and not by vector control activities, because
      organophosphates have never been used for vector control in the area. Our results
      indicate that there are still susceptible anopheline populations to pyrethroids,
      which is consistent with other research from the region. Therefore, there is
      presently no direct threat to vector control. However increased use of
      pyrethroids in agriculture may cause problems for future vector control.

PMID- 16438204
TI  - Three indigenous Thai medicinal plants for control of Aedes aegypti and Culex
      quinquefasciatus.
AB  - The potential larvicidal activity and insect growth regulator (IGR) properties of
      three selected indigenous medicinal Thai plants were tested against two species
      of mosquito with special reference to the late 3rd and early 4th instar larvae
      (L3 and L4, respectively). In case of larvicidal activity, Thevetia peruviana was
      the most potent, followed by Pueraria mirifica, and Butea superba was the least
      effective. In all cases, the late 3rd instar was more susceptible than the early
      4th instar larvae, and the 48-hours exposure yielded more potent larvicidal
      activity than 24-hours exposure. However, at sublethal dosages, both P. mirifica
      and B. superba showed some dispersed effects interfering with ecdysis. A variety
      of toxic effects were observed and recorded in eight categories according to the
      stage of metamorphosis when death occurred. P. mirifica rendered the main
      deleterious effects in the pupa-adult period in both instar of Ae. aegypti and
      Cx. quinquefasciatus, whereas B. superba showed highest effect in black-pupa
      period of the late 3rd instar larval stage. The results were reversed for the
      early 4th instar larvae of both species of mosquito as the main effect appeared
      in the pupa-adult category. The overall results indicated that T. peruviana did
      not show any IGR properties; whereas, P. mirifica and B. superba seemed to
      exhibit the juvenile hormone type activity which resulted in abnormal death at
      various stages of development. B. superba was more promising than P. mirifica,
      and Ae. aegypti was about 2 times more susceptible than Cx. quinquefasciatus. In
      addition, L3 was always more susceptible than L4 with both mosquito species.

PMID- 16438203
TI  - Laboratory colonization of Aedes lineatopennis.
AB  - Aedes lineatopennis, a species member of the subgenus Neomelaniconion, could be
      colonized for more than 10 successive generations from 30 egg batches [totally
      2,075 (34-98) eggs] of wild-caught females. The oviposited eggs needed to be
      incubated in a moisture chamber for at least 7 days to complete embryonation and,
      following immersion in 0.25-2% hay-fermented water, 61-66% of them hatched after
      hatching stimulation. Larvae were easily reared in 0.25-1% hay-fermented water,
      with suspended powder of equal weight of wheat germ, dry yeast, and oatmeal
      provided as food. Larval development was complete after 4-6 days. The pupal stage
      lasted 3-4 days when nearly all pupae reached the adult stage (87-91%). The
      adults had to mate artificially, and 5-day-old males proved to be the best age
      for induced copulation. Three to five-day-old females, which were kept in a paper
      cup, were fed easily on blood from an anesthetized golden hamster that was placed
      on the top-screen. The average number of eggs per gravid female was 63.56 +/-
      22.93 (22-110). Unfed females and males, which were kept in a paper cup and fed
      on 5% multivitamin syrup solution, lived up to 43.17 +/- 12.63 (9-69) and 15.90
      +/- 7.24 (2-39) days, respectively, in insectarium conditions of 27 +/- 2 degrees
      C and 70-80% relative humidity.

PMID- 16438205
TI  - Culex quinquefasciatus in Phitsanulok as a possible vector of nocturnally
      periodic Wuchereria bancrofti transmission in Myanmar immigrants.
AB  - The present study was undertaken in order to study whether Culex quinquefasciatus
      collected in Phitsanulok Province can be an insect host for the development of
      Wuchereria bancrofti larvae. W. bancrofti infected blood from Myanmar workers in
      Mae Sot, Tak Province was fed to mosquitoes by using the artificial membrane
      feeding. An infection of W. bancrofti was found with the highest density of L3 in
      the mosquito thorax on the 14th day after feeding. The infection rate also
      correlated to the density of microfilaria found in the donor's blood. Our results
      showed that Cx. quinquefasciatus in Phitsanulok is a possible vector of
      nocturnally periodic W. bancrofti.

PMID- 16438206
TI  - Brackish-water mollusks of Surat Thani Province, southern Thailand.
AB  - Brackish-water mollusks inhabiting the mangrove areas along the Gulf of Thailand
      of Surat Thani Province were investigated for distribution, abundance and natural
      infections. Nine families and 32 species of brackish-water snails were recovered
      from 14 sampling stations. Species belonging to the genus Ceritidea of the family
      Potamididae were mainly examined and Cerithidea (Cerithideopsilla) Cingulata, C.
      (C.) djadjariensis, and C. (Cerithidea) charbonnieri were naturally infected with
      2 types of trematode cercariae, and one which was undetermined. C. (C.) cingulata
      had the highest infection rate (38.5%). Viewing two snail communities, the first
      community on the mainland and the second on Samui Island in Surat Thani Province,
      28 brackish-water mollusk species were present on the mainland, 15 species were
      evident on Samui Island, and 11 snail species were common to both the mainland
      and Samui Island. Measurement of community similarity based on species presence
      revealed an index of similarity of 0.51. Concerning land use by the local people
      in the station areas investigated, brackish-water snails in Surat Thani Province
      are facing habitat degradation by human use.

PMID- 16438207
TI  - Emergence of Opisthorchis viverrini cercariae from naturally infected Bithynia
      (Digoniostoma) siamensis goniomphalos.
AB  - Under natural conditions, the emergence of Opisthorchis viverrini cercariae from
      naturally infected Bithynia (Digoniostoma) siamensis goniomphalos showed diurnal
      periodicity, peaking between 8:00-10:00 AM. The cercariae did not emerge during
      darkness, but low-intensity light could induce a release. Cercariae shedded from
      each field infected B.(D.) s. goniomphalos was recorded daily. The maximum output
      from one snail was 1,728 cercariae in a day. The total cercarial output from all
      five infected snails was 56,555 and the maximum of total cercariae shed from one
      snail was 27,692. The field-infected B. (D.) s. goniomphalos could survive for 70
      days after the snails were collected.

PMID- 16438208
TI  - The molluscicidal activities of some Euphorbia milii hybrids against the snail
      Indoplanorbis exustus.
AB  - The objective of this study was to observe the molluscicidal activities of
      Euphorbia milli, known as "poysean" in Thailand, against Indoplanorbis exustus.
      Latex from 12 different E. milii hybrids was screened for its molluscicidal
      activities. Indoplanorbis exustus were exposed for 24 and 48 hours to the latex
      at various concentrations ranging from 6 to 25 ppm and mortality rates were
      recorded. Eight hybrids of latex were effective. The six most effective hybrids
      were E. milii Dang-udom, E. milii Arunroong, E. milii Raweechotchuong, E. milii
      Srisompote, E. milii Sri-umporn and E. milii Tongnopakun, which killed all snails
      after 24 hours of exposure. Under the same conditions, latex of E. milii
      Dowpraket and E. milii Promsatid killed 50% of the snails. Such results indicate
      that these 6 hybrids seem promising as natural molluscicidal agents.

PMID- 16438210
TI  - Surveillance of leptospirosis after flooding at Loei Province, Thailand by year
      2002.
AB  - In this surveillance, suspected leptospirosis patients in Loei Hospital, Loei
      Province were studied by conventional methods of cultivation and microscopic
      agglutination test (MAT) during July-October, 2002. It was found that 63% of 64
      admitted patients and 35% of 34 outpatients were found positive by leptospire
      cultivation. Antibodies determined by MAT were positive in 78% of 63 admitted
      patients. Particularly, the five most common agglutinating antibodies were
      reactive with serovars bratislava (57%), autumnalis (48%), new (38%), australis
      (37%) and bangkok (29%). The MAT results of 15 OPD patients were 67% positive
      with the following five serovars, including bratislava (47%), new (20%), bangkok
      (7%), ranarum (7%) and australis (7%). Accordingly, preventive strategies against
      leptospirosis outbreaks after flooding in Thailand should be undertaken,
      including the prompt treatment of the disease in this endemic area.

PMID- 16438209
TI  - Prevalence of dengue fever and dengue hemorrhagic fever in Hospital Tengku Ampuan
      Rahimah, Klang, Selangor, Malaysia.
AB  - Dengue fever and dengue hemorrhagic fever have been known to be endemic and
      reportable diseases in Malaysia since 1971. Major outbreaks occurred in 1973,
      1982 and in 1998. For the past few decades until now. many studies have been
      performed to investigate the importance of these two diseases in Malaysia. A
      retrospective study was carried out in Hospital Tengku Ampuan Rahimah Klang to
      find the prevalence of these diseases. The data was collected from the record
      department of this hospital starting from the year 1999 until 2003 (5 years). A
      total of 6,577 cases of dengue fever and 857 cases of dengue hemorrhagic fever
      were reported. From the year 2000 onwards, cases of dengue fever had increased
      tremendously. However for the year 2001, there was a slight decrease in the
      reported cases. Most cases occurred in 2003, increasing from 674 in 1999 to 2,813
      in 2003. Highest incidence was seen in Malay males more than 12 years of age.
      However, the cases of dengue hemorrhagic fever declined tremendously throughout
      the years. Most cases occurred in 1999 with 674 cases, then declining to only one
      in the year 2001 before it increased to 60 and 72 in the years 2002 and 2003,
      respectively. Most cases occurred in patients above 12 years old, the majority of
      which were Malay males.

PMID- 16438211
TI  - Epitope mapping of monoclonal antibodies specific to serovar of Leptospira, using
      phage display technique.
AB  - Random heptapeptide library displayed by bacteriophage T7 was used to
      characterize epitopes of five monoclonal antibodies that were specific to L.
      australis, L. bangkok, and L. bratislava. Phages selected by biopanning were
      cloned by plaque isolation, and the binding specificity of individual clones was
      confirmed by enzyme-linked immunosorbent assay, before being further amplified
      and checked for phage peptide sequence using PCR and DNA sequencing. Almost all
      of the peptide epitopes were continuous or linear. Interestingly, in phages
      reacting with the monoclonal antibody (MAb) clones F11, F20, 2C3D4, and 8C6C4A12,
      the deduced amino acid sequence of the displayed peptides corresponded to a
      segment of hypothetical protein of the Leptospira genome (L. interrogans serovar
      Lai and Copenhageni). Considering the deduced amino acid sequences of phages
      reacting with the MAb clones F11, F20, 2C3D4, and 8C6C4A12, the consensus motif 
      SKSSRC-, -TLINIF-, -SSKSYR- and -CTPKKSGRC- appeared respectively. No similarity
      was observed among phage reacting with the MAb clone F21. The results demonstrate
      that T7 phage display technique has potential for epitope mapping of leptospiral
      MAbs, and for rapid analysis of the interactions between phage display peptides
      with the MAb. The finding of a phage peptide that binds to MAb with protective
      activity can be further tested as a candidate for leptospirosis vaccine in the
      future.

PMID- 16438212
TI  - Tuberculosis in diabetic patients: a clinical perspective.
AB  - This retrospective and descriptive study was a report on the clinical situation
      of tuberculosis in diabetic patients, with 1,651 patients recruited. The mean age
      of TBDM patients was significantly higher than that of non-diabetic patients
      (p<0.05). Moreover, TBDM patients had a higher ratio of male to female than the
      other group. The significant proportion of TB appeared to increase steadily with
      age in diabetic patients compared to non-diabetic ones (p<0.05). However, they
      showed similarities in terms of sex, race, marital status, present address, and
      occupation. A higher percentage of pulmonary tuberculosis (91.4%) was shown in
      the TBDM group. We found that both groups had no differences in the radiological
      findings, with opacity or cavity of the upper lobe involvement being 89% and 91%
      in TBDM and non-diabetic groups, respectively. TBDM patients were shown to have
      more treatment success (33.3%), particularly the pulmonary type of tuberculosis
      in the longer duration ( 9 months). Further findings demonstrated that a lower
      proportion of the TBDM group defaulted in their treatment (19.8%) and experienced
      resistance to anti-tubercular therapy (1.4%) compared to non-diabetics.

PMID- 16438213
TI  - The association between environmental factors and tuberculosis infection among
      household contacts.
AB  - A cross-sectional study was conducted to determine the association between
      environmental factors and tuberculosis infection among household contacts aged
      less than 15 years in Bangkok, Thailand, between May and December 2003. During
      the study period, 480 household contacts aged under 15 years were identified. The
      prevalence of tuberculosis infection among household contacts was 47.08% (95% CI
      = 42.60-51.56). A generalized estimating equation (GEE) indicated that the risk
      of positive tuberculin skin testing in household contacst was found to increase
      with household crowding. Children living in a crowded household were five times
      more likely to have tuberculosis infection (OR = 5.19, 95% CI = 2.65-8.69). The
      association between environmental factors and tuberculosis infection assists
      community tuberculosis staff in understanding the risks for tuberculosis
      infection in the community and planning appropriate preventive actions based on
      this risk.

PMID- 16438214
TI  - Analysis of Mycobacterium leprae genome: in silico searching for drug targets.
AB  - The author performed a database search to find the recorded complete genes with
      complete sequences of Mycobacterium leprae and studied their homology to human
      genomes by BLAST method. From a total of 35 genes, the potential candidates for
      further target-based drug development were identified.

PMID- 16438215
TI  - Mutations in the gyrA and gyrB genes of fluoroquinolone-resistant Mycobacterium
      tuberculosis from TB patients in Thailand.
AB  - Among fluoroquinolone-resistant Mycobacterium tuberculosis (FQr-MTB) isolates,
      mutation at positions 90, 91, and 94 in gyrA gene and at positions 495, 516, and
      533 in gyrB gene have been frequently reported. In this study, 35 isolates of FQr
      MTB were collected from Siriraj Hospital and Chest Disease Institute. The
      quinolone-resistance-determining regions (QRDR) of gyrA and gyrB genes in all 35
      FQr-MTB isolates and from the H37Ra MTB strain were amplified using polymerase
      chain reaction (PCR). DNA-sequencing and single-strand conformation polymorphism
      (SSCP) were further utilized for characterization of the mutations in the QRDR of
      gyrA and gyrB genes and mutation screening, respectively. From DNA-sequencing, 21
      of 35 (60%) exhibited single-point mutations in different positions, at Ala90Val,
      Ser91Pro, and Asp94(Gly/Ala/His/Asn); and one novel mutation position at Gly88Cys
      in the gyrA gene and Asp495Asn in the gyrB gene. These positions were previously
      frequently reported to be responsible for FQr-MTB. The other 14 FQr-MTB isolates
      (40%) had no mutation. This study is the first report of mutation occurring only
      in the QRDR of the gyrB gene, without prior mutation in the gyrA QRDR among FQr
      MTB isolates. By SSCP analysis for screening of the mutant FQr-MTB, the SSCP
      patterns of mutated FQr-MTB isolates were clearly differentiated from the SSCP
      patterns of FQs-MTB.

PMID- 16438216
TI  - Mutagenicity of Pueraria mirifica Airy Shaw & Suvatabandhu and antimutagenicity
      of Thunbergia laurifolia Linn.
AB  - Thunbergia laurifolia Linn has been reputed to have antitoxic effects for all
      toxic substances. In this present study, we evaluated its effect against the
      mutagenicity induced by aqueous extracts from Pueraria mirifica Airy Shaw &
      Suvatabundhu in male rats. The formation of micronuclei in polychromatic
      erythrocytes was induced by oral administration of an aqueous extract of P.
      mirifica at the doses of 400, 600, and 800 mg/kg to the rats for 30 days. The
      results were that the extracts of P. mirifica at doses of 600 and 800 mg/kg acted
      as a mutagenic agent by inducing higher frequencies of micronuclei as compared to
      the controls. For the antimutagenic test, P. mirifica extract at a dose of 600
      mg/kg (minimal effective dose) was mixed with fresh and dried extracts of T.
      laurifolia in proportions of 7:3 and 1:1, respectively. The results of 4-week
      treatment indicated that aqueous extracts of T. laurifolia, prepared by both
      fresh and dry methods, could significantly inhibit the induction of micronuclei
      as induced by P. mirifica. It could be concluded from the results that, under
      certain circumstances, T. laurifolia exhibits a significant antimutagenic
      activity. The use of P. mirifica and T. laurifolia as fusion herbal medicines is
      suggested.

PMID- 16438217
TI  - The toxicity of a crude enzyme extract from Gliomastix murorum in Swiss Albino
      mice.
AB  - A crude enzyme extract from a fungus, Gliomastix murorum, could be used in the
      synthesis of oligosaccharides that are essential to the food and drug industries.
      This extract may contaminate such products and lead to serious health problems.
      An investigation on the possible toxicity and mutagenic effect of the extract
      from this fungal isolate was carried out in Swiss Albino mice. One hundred and
      50% of the crude enzyme extract were injected intraperitoneally into the mice
      every 2 days for 30 days. Normal saline (0.9%), cultivation medium, and
      cyclophosphamide (80 mg/kg body weight) were given to the control groups. The
      results indicated that the white blood cell count, serum creatinine, and uric
      acid of the treated mice were significantly higher than those of the controls
      (p<0.05), whereas the serum urea-N was lower. For the micronucleus test, mice
      treated with the extract, especially the group received 100% crude enzyme
      extract, showed a higher number of micronuclei in polychromatic erythrocytes, as
      compared to controls. Nevertheless, the micronucleus values were not as high as
      those found in mice treated with cyclophosphamide, the mutagenic agent. It can be
      concluded from the results that crude enzyme extract had minor toxic effects on
      various organ systems tested; more extensive investigation on the safe use of
      this extract is therefore necessary.

PMID- 16438218
TI  - Relationship between serum antioxidant vitamins A, E, and C and lipid profiles in
      priest subjects at the Priest Hospital.
AB  - The serum vitamins A, E, and C (antioxidant vitamins) of 112 priest subjects,
      compared with 90 males and 119 females in a control group, were investigated.
      Subjects for the study were Thai volunteers who attended the Outpatient
      Department, Priest Hospital, Bangkok, for a physical check-up from July to
      September 2003. There was no age difference between the priest group and the
      controls. All serum vitamins, A, E, and C, of the priest group were significantly
      lower than the control group. Statistically significantly higher levels of total
      cholesterol, LDL-C, and LDL-C/HDL-C ratio were found in the priest subjects
      compared with the controls. The median serum retinol concentration in the priest
      subjects was 3.02 micromol/l (range 1.47-4.01 micromol/l) compared with 3.23
      micromol/l (range 1.74-4.57 micromol/l) in the controls (p<0.01). The median
      serum a-tocopherol concentration in the priest subjects was 18.1 mmol/l (range
      5.8-27.3 micromol/l) compared with 19.6 mmol/l (range 7.3-37.7 micromol/l) in the
      controls (p<0.01). The median serum ascorbic acid concentration in the priest
      subjects was 3.74 mg/l (range 0.0-17.0 mg/l) compared with 6.37 mg/l (range 0.0
      18.0 mg/l) in the controls. The median values for retinol, alpha-tocopherol, and
      ascorbic acid serum concentrations in the male priests were lower than the
      control males. A total of 28% and 65% of the priest subjects had decreased alpha
      tocopherol and ascorbic acid levels, while the controls had decreased alpha
      tocopherol and ascorbic acid levels of 20% and 31.5%, respectively. A total of
      67.8% and 54.4% of priest and control subjects, respectively, had cholesterol
      concentrations of > or = 5.18 mmol/l. However, a prevalence of low HDL-C (HDL-C <
      or = 0.91 micromol/l) was found in 1.8% of priest subjects and 1.4% of controls.
      Statistically significant associations were found between alpha-tocopherol,
      cholesterol, LDL-C, triglyceride, and serum retinol. A positive correlation was
      found between age, retinol, and serum alpha-tocopherol. A negative correlation
      was found between cholesterol, HDL-C, LDL-C, and the serum alpha
      tocopherol/cholesterol ratio. In addition, negative correlations were found
      between weight, cholesterol, LDL-C, triglyceride, and the serum alpha
      tocopherol/(cholesterol + triglyceride) ratio in priest and control subjects. The
      results suggest more research should be conducted into the health and nutritional
      problems of both healthy and diseased priest subjects concerning vitamins and
      oxidative stress.

PMID- 16438219
TI  - Hydrophilic and lipophilic antioxidant activities of guava fruits.
AB  - The objectives of this study were to evaluate the hydrophilic antioxidant
      activity (AOAH) and the lipophilic antioxidant activity (AOAL); and their
      correlations with vitamin C, and total phenolic and beta-carotene contents in
      fresh guava fruits of one white flesh clone ('Allahabad Safeda') and three pink
      flesh clones ('Fan Retief', 'Ruby Supreme,' and an advanced selection). A ferric
      reducing antioxidant power assay was used to estimate both AOAH and AOAL from
      methanol and dichloromethane extracts, respectively. The white flesh clone,
      'Allahabad Safeda,' showed higher levels of both AOAH [33.3 microM Trolox
      equivalents (TE)/g fresh weight (FW)] and AOAL (0.25 microM TE/g FW) than the
      pink flesh clones that ranged from 15.5 to 30.4 and from 0.12 to 0.13 microM TE/g
      FW for AOAH and AOAL, respectively. The AOAH was positively correlated with
      vitamin C (r = 0.92, p < 0.01) and total phenolic (r = 0.97, p < 0.01) but was
      negatively correlated with beta-carotene (r = -0.73, p = 0.03). The AOAL was not
      correlated with these antioxidants.

PMID- 16438220
TI  - Health promotion program for the safe use of pesticides in Thai farmers.
AB  - The purpose of this study was to determine the knowledge, attitudes and practices
      (KAP) concerning the safe use of pesticides of Thai farmers in Don Kha
      subdistrict, Bang Phae district, Ratchaburi Province. Thirty-three voluntary Thai
      farmers of thirty-three farming families, recruited by convenience sampling,
      participated in a training program for six months. Data were collected by
      questionnaire interviews, and KAP on the safe use of pesticides were compared by
      paired t-test. Research findings showed that the mean scores of KAP in the
      posttest were significantly higher than the pretest. The results of this study
      provided health professionals with information to develop more effective
      prevention and intervention programs. To prevent illness, the most important role
      of health officers should to be focus on education and information for
      individuals, families, and communities.

PMID- 16438221
TI  - Reduction of low back muscular discomfort through an applied ergonomics
      intervention program.
AB  - An applied ergonomics intervention program (AEIP) was conducted with male
      employees who work in the pressing and storage sections of a metal auto parts
      factory in eastern Thailand. The objective of this study was to reduce worker
      muscular discomfort at the low back. The study design was a participatory
      research approach, with quasi-experimental pretest-posttest, and with a non
      equivalent control group. Thirty-five persons participated in the AEIP (AEIP
      group) and 17 persons did not (non-AEIP group). The AEIP was composed of three
      major categories: (1) top management support; (2) equipment designed for
      workstations and manual material handling; and (3) administrative intervention,
      training, and health education. Muscle activity was measured by surface
      electromyography of the left and right erector spinae, and multifidus muscles;
      and evaluated by multivariate test for dependent samples (paired observation) and
      for independent samples. After the AEIP, the low back muscular loads of the AEIP
      group was significantly reduced, while those of the non-AEIP group were not.
      Comparison of the means of percentage maximum voluntary contractions (% MVC) of
      low back muscular activity between the AEIP group and non-AEIP group indicated
      that the AEIP group had significantly reduced low back muscular load, with a 95%
      confidence level (p-value < 0.05).

PMID- 16438222
TI  - Antioxidant in plasma of hemoglobin-E trait.
AB  - A study of antioxidant levels among Thai subjects with a hemoglobin E trait was
      undertaken. The objective of this study was to determine whether the antioxidant
      level would be disturbed in the HbE condition. All 185 volunteer subjects, 171
      normal healthy subjects and 14 HbE carriers were recruited. For each case, an
      antioxidant determination was performed using the Trolox equivalent antioxidant
      capacity (TEAC) method. According to this study, the average antioxidant level in
      the healthy group was 3.439 +/- 0.220 mM Trolox equivalent, and in HbE trait
      group was 3.276 +/- 0.209 mM Trolox equivalent. There was a significant decrease
      of the antioxidant level in the HbE trait group (p = 0.008).

PMID- 16438223
TI  - Ultrastructural changes of pancreatic islets microcirculation in nonobese
      diabetic (NOD) mice.
AB  - The objective of this study was to investigate the ultrastructural changes of
      vascular pancreatic islets using a transmission electron microscopic technique.
      The major ultrastructural changes of microvessel in NOD mice are indicated by the
      swelling and vacuolization of the endothelial cell. Swollen cells are the first
      noticeable lesion of the cell response in reversible degeneration that is caused
      by the failure of homeostatic control. Loss in endothelial cell homeostasis is
      primarily a marker of endothelial dysfunction that plays a key role in the
      pathogenesis of diabetic vascular disease by losing the control of vascular tone.
      Diabetes also associates with an increased generation of oxygen-derived free
      radicals that may impair vasodilatation through the inactivation of vasodilators.
      In conclusion, consistent with a hypothesis that loss of the modulatory role of
      the endothelium may be a critical and initiating factor in the development of
      diabetic vascular disease, the ultrastructural changes in this study may indicate
      the first sign of endothelial dysfunction. This dysfunction correlates to the
      relationship between diabetes and reversible lesions of vessels in NOD mice,
      making for a better understanding of the pathophysiology of diabetic vascular
      disease to set the stage for further investigation to restore endothelial
      dysfunction in diabetes.

PMID- 16438224
TI  - A novel ex vivo heart model for the assessment of cardiac pacing systems.
AB  - BACKGROUND: Advances in endocardial device design have been limited by the
      inability to visualize the device-tissue interface. The purpose of this study was
      to assess the validity of an isolated heart approach, which allows direct ex vivo
      intracardiac visualization, as a research tool for studying endocardial pacing
      systems. METHOD OF APPROACH: Endocardial pacing leads were implanted in the right
      atria and ventricles of intact swine (n = 8) under fluoroscopic guidance. After
      collection of pacing and sensing performance parameters, the hearts were excised
      with the leads intact and reanimated on the isolated heart apparatus, and
      parameters again recorded. RESULTS: Atrial ex vivo parameters significantly
      decreased compared with in vivo measurements: P-wave amplitudes by 39%, slew
      rates by 61%, and pacing impedances by 42% (p < 0.05 for each). Similarly,
      several ventricular ex vivo parameters decreased: R-wave amplitudes by 39%, slew
      rates by 62%, and pacing impedances by 31%. In contrast, both atrial (4.4 +/- 2.8
      vs 3.3 +/- 2.8 V; p = ns) and ventricular thresholds increased (1.2 +/- 0.7 vs
      0.6 +/- 0.1 V; p < 0.05 for all). Three distinct phenomena were observed at the
      lead-tissue interface. Normal implants (70%) demonstrated minimal tissue
      distortion and resulted in elevated impedance and threshold values. Three
      implants (13%) resulted in severe tissue distortion and/or tissue wrapping and
      were associated with highly elevated pacing parameters. Tissue coring occurred in
      four implants (17%) where the lead would spin freely in the tissue after
      overtorquing of the lead. CONCLUSIONS: The utility of the isolated heart approach
      was demonstrated as a tool for the design and assessment of the performance of
      endocardial pacing systems. Specifically, the ability to visualize device-heart
      interactions allows new insights into the impact of product design and clinical
      factors on lead performance and successful implantation.

PMID- 16438225
TI  - Detection of heart murmurs using wavelet analysis and artificial neural networks.
AB  - This paper presents the algorithm and technical aspects of an intelligent
      diagnostic system for the detection of heart murmurs. The purpose of this
      research is to address the lack of effectively accurate cardiac auscultation
      present at the primary care physician office by development of an algorithm
      capable of operating within the hectic environment of the primary care office.
      The proposed algorithm consists of three main stages. First; denoising of input
      data (digital recordings of heart sounds), via Wavelet Packet Analysis. Second;
      input vector preparation through the use of Principal Component Analysis and
      block processing. Third; classification of the heart sound using an Artificial
      Neural Network. Initial testing revealed the intelligent diagnostic system can
      differentiate between normal healthy heart sounds and abnormal heart sounds
      (e.g., murmurs), with a specificity of 70.5% and a sensitivity of 64.7%.

PMID- 16438226
TI  - Simulated bioprosthetic heart valve deformation under quasi-static loading.
AB  - For more than 40 years, the replacement of diseased natural heart valves with
      prosthetic devices has dramatically extended the quality and length of the lives
      of millions of patients worldwide. However, bioprosthetic heart valves (BHV)
      continue to fail due to structural failure resulting from poor tissue durability
      and faulty design. Clearly, an in-depth understanding of the biomechanical
      behavior of BHV at both the tissue and functional prosthesis levels is essential
      to improving BHV design and to reduce rates of failure. In this study, we
      simulated quasi-static BHV leaflet deformation under 40, 80, and 120 mm Hg quasi
      static transvalvular pressures. A Fung-elastic material model was used that
      incorporated material parameters and axes derived from actual leaflet biaxial
      tests and measured leaflet collagen fiber structure. Rigorous experimental
      validation of predicted leaflet strain field was used to validate the model
      results. An overall maximum discrepancy of 2.36% strain between the finite
      element (FE) results and experiment measurements was obtained, indicating good
      agreement between computed and measured major principal strains. Parametric
      studies utilizing the material parameter set from one leaflet for all three
      leaflets resulted in substantial variations in leaflet stress and strain
      distributions. This result suggests that utilization of actual leaflet material
      properties is essential for accurate BHV FE simulations. The present study also
      underscores the need for rigorous experimentation and accurate constitutive
      models in simulating BHV function and design.

PMID- 16438227
TI  - A thin film nitinol heart valve.
AB  - In order to create a less thrombogenic heart valve with improved longevity, a
      prosthetic heart valve was developed using thin film nitinol (NiTi). A
      "butterfly" valve was constructed using a single, elliptical piece of thin film
      NiTi and a scaffold made from Teflon tubing and NiTi wire. Flow tests and
      pressure readings across the valve were performed in vitro in a pulsatile flow
      loop. Bio-corrosion experiments were conducted on untreated and passivated thin
      film nitinol. To determine the material's in vivo biocompatibility, thin film
      nitinol was implanted in pigs using stents covered with thin film NiTi. Flow
      rates and pressure tracings across the valve were comparable to those through a
      commercially available 19 mm Perimount Edwards tissue valve. No signs of
      corrosion were present on thin film nitinol samples after immersion in Hank's
      solution for one month. Finally, organ and tissue samples explanted from four
      pigs at 2, 3, 4, and 6 weeks after thin film NiTi implantation appeared without
      disease, and the thin film nitinol itself was without thrombus formation.
      Although long term testing is still necessary, thin film NiTi may be very well
      suited for use in artificial heart valves.

PMID- 16438228
TI  - Numerical validation of linear accelerometer systems for the measurement of head
      kinematics.
AB  - The purpose of this study was to analytically exploit the capabilities of head
      mounted systems instrumented with linear accelerometers (ACs) for field use in
      redundant configurations. We simulated different headsets equipped with uni-, bi-
      or triaxial sensors with a number of axes that lie in the range of 12-24; the ACs
      were located on a hemispherical surface by adopting a priori criterion while
      their orientation was randomized. In addition, for a comparative purpose the nine
      accelerometer scheme (one triaxial AC and three biaxial ACs addressed in the
      following as "3-2-2-2 configuration") was also analyzed in the present paper. We
      simulated and statistically assessed the performances of hemispherical headsets
      in the test case of a healthy subject walking freely at normal pace over level
      ground. The numerical results indicated that a well designed instrumented headset
      can retrieve the angular acceleration and (a0-g) component with rms errors of
      about 2% and 0.5%, respectively, and angular velocity with a drift error of about
      20% in a 6 s trial. On the contrary, the pose of the headset cannot be evaluated
      because of the drift induced by the integration process. In general, we can state
      that headsets with uni-, bi- or triaxial ACs have comparable performances. The
      main implications of the above-mentioned observations are (a) neither expensive
      triaxial ACs nor assembling procedure based on the use of orthogonal mounting
      blocks are needed; (b) redundant arrays of low-cost uni- or biaxial ACs can
      effectively be used to reach adequate performances in biomechanical studies where
      head acceleration and velocity are investigated; (c) while estimates of angular
      acceleration with accelerometers are accurate, estimations of angular velocities,
      linear velocities and pose are not.

PMID- 16438229
TI  - Biomechanical evaluation of a novel lumbosacral axial fixation device.
AB  - BACKGROUND: Interbody arthrodesis is employed in the lumbar spine to eliminate
      painful motion and achieve stability through bony fusion. Bone grafts, metal
      cages, composite spacers, and growth factors are available and can be placed
      through traditional open techniques or minimally invasively. Whether placed
      anteriorly, posteriorly, or laterally, insertion of these implants necessitates
      compromise of the anulus--an inherently destabilizing procedure. A new axial
      percutaneous approach to the lumbosacral spine has been described. Using this
      technique, vertical access to the lumbosacral spine is achieved percutaneously
      via the presacral space. An implant that can be placed across a motion segment
      without compromise to the anulus avoids surgical destabilization and may be
      advantageous for interbody arthrodesis. The purpose of this study was to evaluate
      the in vitro biomechanical performance of the axial fixation rod, an anulus
      sparing, centrally placed interbody fusion implant for motion segment
      stabilization. METHOD OF APPROACH: Twenty-four bovine lumbar motion segments were
      mechanically tested using an unconstrainedflexibility protocol in sagittal and
      lateral bending, and torsion. Motion segments were also tested in axial
      compression. Each specimen was tested in an intact state, then drilled
      (simulating a transaxial approach to the lumbosacral spine), then with one of two
      axial fixation rods placed in the spine for stabilization. The range of motion,
      bending stiffness, and axial compressive stiffness were determined for each test
      condition. Results were compared to those previously reported for femoral ring
      allografts, bone dowels, BAK and BAK Proximity cages, Ray TFC, Brantigan ALIF and
      TLIF implants, the InFix Device, Danek TIBFD, single and double Harms cages, and
      Kaneda, Isola, and University plating systems. RESULTS: While axial drilling of
      specimens had little effect on stiffness and range of motion, specimens implanted
      with the axial fixation rod exhibited significant increases in stiffness and
      decreases in range of motion relative to intact state. When compared to existing
      anterior, posterior, and interbody instrumentation, lateral and sagittal bending
      stiffness of the axial fixation rod exceeded that of all other interbody devices,
      while stiffness in extension and axial compression were comparable to plate and
      rod constructs. Torsional stiffness was comparable to other interbody constructs
      and slightly lower than plate and rod constructs. CONCLUSIONS: For stabilization
      of the L5-S1 motion segment, axial placement of implants offers potential
      benefits relative to traditional exposures. The preliminary biomechanical data
      from this study indicate that the axial fixation rod compares favorably to other
      devices and may be suitable to reduce pathologic motion at L5-S1, thus promoting
      bony fusion.

PMID- 16438230
TI  - A light weight compliant hand mechanism with high degrees of freedom.
AB  - This paper presents the design and prototyping of an inherently compliant
      lightweight hand mechanism. The hand mechanism itself has 15 degrees of freedom
      and five fingers. Although the degrees of freedom in each finger are coupled,
      reducing the number of independent degrees of freedom to 5, the 15 degrees of
      freedom of the hand could potentially be individually actuated. Each joint
      consists of a novel flexing mechanism that is based on the loading of a
      compression spring in the axial and transverse direction via a cable and conduit
      system. Currently, a bench top version of the prototype is being developed; the
      three joints of each finger are coupled together to simplify the control system.
      The current control scheme under investigation simulates a control scheme where
      myoelectric signals in the wrist flexor and extensor muscles are converted in to
      x and y coordinates on a control scheme chart. Static load-deformation analysis
      of finger segments is studied based on a 3-dimensional model without taking the
      stiffener into account, and the experiment validates the simulation.

PMID- 16438231
TI  - Design and analysis of orthogonally compliant features for local contact pressure
      relief in transtibial prostheses.
AB  - A very attractive advantage of manufacturing prosthetic sockets using solid
      freeform fabrication is the freedom to introduce design solutions that would be
      difficult to implement using traditional manufacturing techniques. Such is the
      case with compliant features embedded in amputee prosthetic sockets to relieve
      contact pressure at the residual limb-socket interface. The purpose of this study
      was to present a framework for designing compliant features to be incorporated
      into transtibial sockets and manufacturing prototypes using selective laser
      sintering (SLS) and Duraform material. The design process included identifying
      optimal compliant features using topology optimization algorithms and integrating
      these features within the geometry of the socket model. Using this process, a
      compliant feature consisting of spiral beams and a supporting external structure
      was identified. To assess its effectiveness in reducing residual limb-socket
      interface pressure, a case study was conducted using SLS manufactured prototypes
      to quantify the difference in interface pressure while a patient walked at his
      self-selected pace with one noncompliant and two different compliant sockets. The
      pressure measurements were performed using thin pressure transducers located at
      the distal tibia and fibula head. The measurements revealed that the socket with
      the greatest compliance reduced the average and peak pressure by 22% and 45% at
      the anterior side distal tibia, respectively, and 19% and 23% at the lateral side
      of the fibula head, respectively. These results indicate that the integration of
      compliant features within the socket structure is an effective way to reduce
      potentially harmful contact pressure and increase patient comfort.

PMID- 16438232
TI  - Novel stent for dacryocystorhinostomy (DCR) and other surgical applications.
AB  - In summary, this project proposes to explore the feasibility of a new temporary
      implant and surgical technique to improve the DCR procedure. This is a
      significant improvement over current DCR practice for the following primary
      reasons: (1) it eliminates the risk of injury to both the eye and upper lacrimal
      system; (2) it permits tear flow into the nose immediately following surgery,
      potentially 6 months earlier than current practice and procedure, which
      frequently does not re-establish normal tear flow until stents are removed. Plans
      have been made to implant stents of different sizes and proportions into cadavers
      in order to test implantation and removal of the stent via external and
      intranasal approaches.

PMID- 16438233
TI  - Tissue characterization for improved external penile occlusive device design.
AB  - This study is motivated by the need for quantitative data on the material
      properties of the penis in order to develop an optimal design for an external
      penile occlusive device (EPOD) for the treatment of urinary incontinence.

PMID- 16438234
TI  - High capacity implantable data recorders: system design and experience in canines
      and Denning black bears.
AB  - BACKGROUND: Implantable medical devices have increasingly large capacities for
      storing patient data as a diagnostic aid and to allow patient monitoring.
      Although these devices can store a significant amount of data, an increased
      ability for data storage was required for chronic monitoring in recent
      physiological studies. METHOD OF APPROACH: Novel high capacity implantable data
      recorders were designed for use in advanced physiological studies of canines and
      free-ranging black bears. These hermitically sealed titanium encased recorders
      were chronically implanted and programmed to record intrabody broadband
      electrical activity to monitor electrocardiograms and electromyograms, and single
      axis acceleration to document relative activities. RESULTS: Changes in cardiac T
      wave morphology were characterized in the canines over a 6 month period,
      providing new physiological data for the design of algorithms and filtering
      schemes that could be employed to avoid inappropriate implantable defibrillator
      shocks. Unique characteristics of bear hibernation physiology were successfully
      identified in the black bears, including: heart rate, respiratory rate, gross
      body movement, and shiver An unanticipated high rejection rate of these devices
      occurred in the bears, with five of six being externalized during the
      overwintering period, including two devices implanted in the peritoneal cavity.
      CONCLUSIONS: High capacity implantable data recorders were designed and utilized
      for the collection of long-term physiological data in both laboratory and extreme
      field environments. The devices described were programmable to accommodate the
      diverse research protocols. Additionally, we have described substantial
      differences in the response of two species to a common device. Variations in the
      foreign body response of different mammals must be identified and taken into
      consideration when choosing tissue-contacting materials in the application of
      biomedical technology to physiologic research.

PMID- 16438235
TI  - A prototype manipulator for magnetic resonance-guided interventions inside
      standard cylindrical magnetic resonance imaging scanners.
AB  - The aim of this work is to develop a remotely controlled manipulator to perform
      minimally invasive diagnostic and therapeutic interventions in the abdominal and
      thoracic cavities, with real-time magnetic resonance imaging (MRI) guidance
      inside clinical cylindrical MR scanners. The manipulator is composed of a three
      degree of freedom Cartesian motion system, which resides outside the gantry of
      the scanner, and serves as the holder and global positioner of a three degree of
      freedom arm which extends inside the gantry of the scanner At its distal end, the
      arm's end-effector can carry an interventional tool such as a biopsy needle,
      which can be advanced to a desired depth by means of a seventh degree of freedom.
      These seven degrees of freedom, provided by the entire assembly, offer extended
      manipulability to the device and a wide envelope of operation to the user, who
      can select a trajectory suitable for the procedure. The device is constructed of
      nonmagnetic and nonconductive fiberglass, and carbon fiber composite materials,
      to minimize artifacts and distortion on the MR images as well as eliminate
      effects on its operation from the high magnetic field and the fast switching
      magnetic field gradients used in MR imaging. A user interface was developed for
      man-in-the-loop control of the device using real-time MR images. The user
      interface fuses all sensor signals (MR and manipulator information) in a
      visualization, planning, and control command environment. Path planning is
      performed with graphical tools for setting the trajectory of insertion of the
      interventional tool using multislice and/or three dimensional MR images which are
      refreshed in real time. The device control is performed with an embedded computer
      which runs real-time control software. The manipulator compatibility with the MR
      environment and image-guided operation was tested on a 1.5 T MR scanner.

PMID- 16438236
TI  - Design and application of compliant mechanisms for surgical tools.
AB  - This paper introduces the benefits of exploiting elasticity in the engineering
      design of surgical tools, in general, and of minimally invasive procedures, in
      particular. Compliant mechanisms are jointless mechanisms that rely on elastic
      deformation to transmit forces and motion. The lack of traditional joints in
      these single-piece flexible structures offers many benefits, including the
      absence of wear debris, pinch points, crevices, and lubrication. Such systems are
      particularly amenable to embedded sensing for haptic feedback and embedded
      actuation with active-material actuators. The paper provides an overview of
      design synthesis methods developed at the Compliant Systems Design Laboratory and
      focuses specifically on surgical applications. Compliant systems have potential
      to integrate. well within the constraints of laparoscopic procedures and
      telerobotic surgery. A load-path representation is used within a genetic
      algorithm to solve two gripper example problems. In addition, the paper
      illustrates the design and construction of an organ (kidney) manipulator for use
      in minimally invasive procedures.

PMID- 16438237
TI  - Design of a multifunctional compliant instrument for minimally invasive surgery.
AB  - A new multifunctional compliant instrument has been designed for use in minimally
      invasive surgery. The instrument combines scissors and forceps into a single
      multifunctional device. The main advantage of using multifunctional instruments
      for minimally invasive surgery is that instrument exchanges can be reduced, thus
      reducing procedure time and risk of inadvertent tissue injury during instrument
      exchanges. In this paper, the length, width, and thickness of the multifunctional
      compliant mechanism tool tip is optimized to maximize the jaw opening and the
      grasping force. The optimized design is then modeled to simulate the stresses
      encountered in the scissors mode. A 5.0 mm diameter stainless steel prototype is
      fabricated using electro-discharge machining and is shown to grasp and cut
      successfully.

PMID- 16438238
TI  - An improved device for posterior rhinomanometry to measure nasal resistance.
AB  - Rhinomanometry is a method for measuring nasal resistance for the purpose of
      providing an objective evaluation of nasal patency. Posterior rhinomanometry is
      accomplished without the use of a mask, thus allowing the patient to breathe
      naturally. Here, we report on the improvements we have made to the existing
      posterior rhinomanometry system. In this system, nasal airflow is measured
      indirectly by measuring the pressure differential across a small mesh window in
      the body plethysmograph. We have calibrated this measurement and developed
      software that automatically provides the correct values for all airflow rates.
      Also, we have developed software that automatically corrects for the phase shift
      caused by the plethysmograph structure. These refinements should provide more
      accurate values for nasal resistance.

PMID- 16438239
TI  - A device for assessment of hand and wrist coronal plane strength.
AB  - Diagnostic and rehabilitative assessments of hand function commonly omit
      measurement of twisting strength even though many activities of daily living
      require turning handles, lids, and objects of many sizes. A simple device to
      quantify twisting strength was designed and constructed to establish normative
      data and test hypotheses about hand function. The instrument is easy to use and
      includes an electronic torsional load cell and disks of several sizes. Tests were
      conducted on the dominant and nondominant hands of 64 normal subjects and 13
      arthritic patients with arthritis of the thumb carpometacarpal joint. Hands were
      tested with disks ranging in diameter from 2.5 to 12.5 cm. A three-way repeated
      measures analysis showed that gender (p < 0.001), handedness (p < 0.001), and
      disk size (p < 0.001) had significant effects. There was no difference between
      radial and ulnar deviation strengths (p = 0.365). The arthritic group had
      significantly reduced strength (p < 0.02). Nine subjects were tested twice, with
      1 day between tests: no differences occurred between the first and second testing
      (p = 0.930). The ability to distinguish the test groups with reproducible results
      proves that the device fulfills all basic requirements; continued testing and
      development are warranted.

PMID- 16438240
TI  - Automated knot tying for fixation in minimally invasive, robot-assisted cardiac
      surgery.
AB  - Cardiovascular disease (CVD) is perhaps the most significant worldwide health
      issue. While open-heart surgery remains the predominant treatment, significant
      advancements have been made in minimally invasive surgery (MIS) and minimally
      invasive robot-assisted (MIRA) surgery. MIRA techniques offer many advantages
      over open-heart procedures and have extended the capabilities of MIS. However,
      these benefits come at the cost of increased operating times due to time spent
      tying knots. The additional bypass time limits patient access and is the most
      significant barrier to the adoption of MIRA techniques. This research seeks to
      overcome this barrier by designing a device for MIRA cardiac procedures that
      automates the knotting of sutures. If this task can be automated while ensuring
      the delivery of high-quality knots, great progress can be made in transforming
      the field. MIRA cardiac procedures can move from novel procedures performed by a
      select group of surgeons on a limited pool of patients to a viable alternative
      available to the majority of patients with CVD. In this research we propose a
      design for a self-contained device that delivers a locking knot. Results suggest
      that consistent knots can be delivered at a time savings of 12.5% and 26.4% over
      manual knots for trained and untrained users of a surgical robot, respectively.

PMID- 16438241
TI  - Design of a robotic gait trainer using spring over muscle actuators for ankle
      stroke rehabilitation.
AB  - Repetitive task training is an effective form of rehabilitation for people
      suffering from debilitating injuries of stroke. We present the design and working
      concept of a robotic gait trainer (RGT), an ankle rehabilitation device for
      assisting stroke patients during gait. Structurally based on a tripod mechanism,
      the device is a parallel robot that incorporates two pneumatically powered,
      double-acting, compliant, spring over muscle actuators as actuation links which
      move the ankle in dorsiflex ion/plantarflexion and inversion/eversion. A unique
      feature in the tripod design is that the human anatomy is part of the robot, the
      first fixed link being the patient's leg. The kinematics and workspace of the
      tripod device have been analyzed determining its range of motion. Experimental
      gait data from an able-bodied person wearing the working RGT prototype are
      presented.

PMID- 16438242
TI  - Design and simulation of a pneumatic, stored-energy, hybrid orthosis for gait
      restoration.
AB  - Loss of mobility due to lower limb paralysis is a common result of thoracic level
      spinal cord injury. Functional electrical stimulation (FES) can restore primitive
      gait in the vicinity of a wheelchair by using electrical stimulation to generate
      muscle contractions. A new concept for FES-assisted gait is presented that
      combines electrical stimulation with an orthosis that contains a fluid power
      system to store and transfer energy during the gait cycle. The energy storage
      orthosis (ESO) can be driven through a complete gait cycle using only stimulation
      of the quadriceps muscles. The conceptual design of the ESO was completed and
      implemented in a dynamic simulation model and in a benchtop prototype for
      engineering measurements. No studies were conducted with human subjects. The
      results demonstrate the potential of the ESO concept for a feasible gait-assist
      system and the validity of the simulation model as a means for designing the
      system.

PMID- 16438243
TI  - Regression techniques for the prediction of lower limb kinematics.
AB  - This work presents a novel and extensive investigation of mathematical regression
      techniques, for the prediction of laboratory-type kinematic measurements during
      human gait, from wearable measurement devices, such as gyroscopes and
      accelerometers. Specifically, we examine the hypothesis of predicting the
      segmental angles of the legs (left and right foot, shank and thighs), from
      rotational foot velocities and translational foot accelerations. This first
      investigation is based on kinematic data emulated from motion-capture laboratory
      equipment. We employ eight established regression algorithms with different
      properties, ranging from linear methods and neural networks with polynomial
      support and expanded nonlinearities, to radial basis functions, nearest neighbors
      and kernel density methods. Data from five gait cycles of eight subjects are used
      to perform both inter-subject and intra-subject assessments of the prediction
      capabilities of each algorithm, using cross-validation resampling methods.
      Regarding the algorithmic suitability to gait prediction, results strongly
      indicate that nonparametric methods, such as nearest neighbors and kernel density
      based, are particularly advantageous. Numerical results show high average
      prediction accuracy (rho = 0.98/0.99, RMS = 5.63 degrees/2.30 degrees, MAD = 4.43
      degrees/1.52 degrees for inter/intra-subject testing). The presented work
      provides a promising and motivating investigation on the feasibility of cost
      effective wearable devices used to acquire large volumes of data that are
      currently collected only from complex laboratory environments.

PMID- 16438244
TI  - A continuous loading apparatus for measuring three-dimensional stiffness of ankle
      foot orthoses.
AB  - This paper describes a novel device to evaluate the mechanical properties of
      ankle foot orthoses (AFOs). The apparatus permits the application to AFOs of
      continuous three-dimensional (3D) movements between specified and settable
      endpoints. Using an x-y robot with a rotary stage and a six-component load cell,
      characteristic displacement versus reaction force curves can be generated and
      consequently the ankle moments can be determined as a function of dorsi/plantar
      flexion, inv/eversion and int/external rotation. Representative curves for two
      polypropylene lateral leaf AFOs, different in shape but produced for the same leg
      by a skilled orthotist, are presented to illustrate the capabilities of the novel
      testing system. The metrological investigation showed that the apparatus creates
      a highly repeatable data set (uncertainty < or = 1% FSO).

PMID- 16438245
TI  - Passive wireless MEMS microphones for biomedical applications.
AB  - This paper introduces passive wireless telemetry based operation for high
      frequency acoustic sensors. The focus is on the development, fabrication, and
      evaluation of wireless, battery-less SAW-IDT MEMS microphones for biomedical
      applications. Due to the absence of batteries, the developed sensors are small
      and as a result of the batch manufacturing strategy are inexpensive which enables
      their utilization as disposable sensors. A pulse modulated surface acoustic wave
      interdigital transducer (SAW-IDT) based sensing strategy has been formulated. The
      sensing strategy relies on detecting the ac component of the acoustic pressure
      signal only and does not require calibration. The proposed sensing strategy has
      been successfully implemented on an in-house fabricated SAW-IDT sensor and a
      variable capacitor which mimics the impedance change of a capacitive microphone.
      Wireless telemetry distances of up to 5 centimeters have been achieved. A silicon
      MEMS microphone which will be used with the SAW-IDT device is being
      microfabricated and tested. The complete passive wireless sensor package will
      include the MEMS microphone wire-bonded on the SAW substrate and interrogated
      through an on-board antenna. This work on acoustic sensors breaks new ground by
      introducing high frequency (i.e., audio frequencies) sensor measurement utilizing
      SAW-IDT sensors. The developed sensors can be used for wireless monitoring of
      body sounds in a number of different applications, including monitoring breathing
      sounds in apnea patients, monitoring chest sounds after cardiac surgery, and for
      feedback sensing in compression (HFCC) vests used for respiratory ventilation.
      Another promising application is monitoring chest sounds in neonatal care units
      where the miniature sensors will minimize discomfort for the newborns.

PMID- 16438246
TI  - A motorized microdrive for recording of neural ensembles in awake behaving rats.
AB  - The recording of neural ensembles in awake, behaving rats has been an extremely
      successful experimental paradigm, providing demonstrable scientific advances.
      Dynamic control of the position of the implanted electrodes is of key importance
      as mobile electrodes provide a better signal-to-noise ratio and a better cell/
      electrode yield than nonmobile electrodes. Here we describe the use of low cost,
      soon to be commercially available dc motors to successfully control the depth of
      electrodes. The prototype designed is approximately 30 mm in diameter and 50 mm
      in length and weighed about 30 gms. This paper presents the results of linear
      displacements of electrodes achievable with this motorized microdrive.

PMID- 16438247
TI  - SUNA's response to recent national disasters.

PMID- 16438248
TI  - Choices.

PMID- 16438249
TI  - Urolithiasis/nephrolithiasis: what's it all about?
AB  - Urolithiasis (urinary tract calculi or stones) and nephrolithiasis (kidney
      calculi or stones) are well-documented common occurrences in the general
      population of the United States. The etiology of this disorder is multifactorial
      and is strongly related to dietary lifestyle habits or practices. Proper
      management of calculi that occur along the urinary tract includes investigation
      into causative factors in an effort to prevent recurrences. Urinary calculi or
      stones are the most common cause of acute ureteral obstruction. Approximately 1
      in 1,000 adults in the United States are hospitalized annually for treatment of
      urinary tract stones, resulting in medical costs of approximately dollar 2
      billion per year (Ramello, Vitale, & Marangella, 2000; Tanagho & McAninch, 2004).

PMID- 16438250
TI  - The role of diet in the prevention of common kidney stones.
AB  - Current dietary recommendations for patients who form kidney stones are
      discussed. Focusing on the most common kidney stone types, calcium oxalate and
      uric acid, the rationale for dietary changes are described based on the renal and
      urine physiology.

PMID- 16438251
TI  - Minimally invasive and surgical management of urinary stones.
AB  - First-line therapy for urinary stones typically involves minimally invasive
      surgical procedures for obstructing stones that cause symptoms and do not pass
      spontaneously in a reasonable time. Treatment decisions are based upon suspected
      stone type, size, location, renal anatomy, and renal function. Comprehensive
      management of urinary lithiasis necessitates collaboration between the urologist,
      urology health care professionals, and medical colleagues that possess knowledge
      of medical treatment.

PMID- 16438252
TI  - Urinary stones and Crohn's disease.
AB  - Urinary stones, renal and bladder, are common in the general population of the
      United States. The pathophysiology of Crohn's disease and therapeutic
      interventions can contribute to the development of kidney stones usually
      secondary to malabsorption. Knowledge of these effects is important when caring
      for patients with urinary stones and intestinal disease.

PMID- 16438253
TI  - Uses of qualitative research, or so what good is it?

PMID- 16438254
TI  - Getting ready for certification: voiding dysfunction.

PMID- 16438255
TI  - July 7th--reactions to London bombings.

PMID- 16438256
TI  - News briefs on prostate cancer, alcoholism, osteoporosis, and drug updates.

PMID- 16438257
TI  - Update on infections you can get from pets.
AB  - Owning and caring for a pet should be an enjoyable experience. Be a responsible
      pet owner and keep your pet healthy. By keeping your pet healthy and following a
      few simple preventive measures, you can protect you and your family against
      zoonotic diseases.

PMID- 16438258
TI  - Attending to weak signals: the leader's challenge.
AB  - Halverson and Isham (2003) quote sources that report the accidental death rate of
      simply being in a hospital is " ... four hundred times more likely than your risk
      of death from traveling by train, forty times higher than driving a car, and
      twenty times higher than flying in a commercial aircraft" (p. 13). High
      reliability organizations such as nuclear power plants and aircraft carriers have
      been pioneers in the business of recognizing weak signals. Weike and Sutcliffe
      (2001) note that high-reliability organizations distinguish themselves from
      others because of their mindfulness which enables them to see the significance of
      weak signals and to give strong interventions to weak signals. To act mindfully,
      these organizations have an underlying mental model of continually updating,
      anticipating, and focusing the possibility of failure using the intelligence that
      weak signals provides. Much of what happens is unexpected in health care.
      However, with a culture that is continually looking for weak signals, and
      intervenes and rescues when these signals are detected, the unexpected happens
      less often. This is the epitome of how leaders can build a culture of safety that
      focuses on recognizing the weak signals to manage the unforeseen.

PMID- 16438260
TI  - Katrina and Mississippi nurses--first person accounts.

PMID- 16438261
TI  - An introduction to minimum intervention dentistry.
AB  - Minimum intervention dentistry (MI) can be defined as a philosophy of
      professional care concerned with the first occurrence, early detection, and
      earliest possible cure of disease on micro levels, followed by minimally
      invasive, patient-friendly treatment to repair irreversible damage caused by such
      disease. The benefit for patients from MI lies in better oral health through
      disease healing and not merely on symptom relief. Furthermore, minimally invasive
      treatment assists in reducing widespread patient dental anxieties. MI has the
      potential for dentists to apply a more conservative approach to caries treatment
      and simultaneously offer patients less invasive, health-oriented treatment
      options.

PMID- 16438262
TI  - Botulinum toxins in dentistry--the new paradigm for masticatory muscle
      hypertonicity.
AB  - A variety of factors, such as stress, hormones, diet, drugs, trauma, and certain
      neuromuscular diseases, can lead to an increase in sympathetic muscle tone, which
      results in masticatory muscle hypertonicity and parafunction. Dentists have
      traditionally attempted to treat and prevent this transient disease with methods
      that are expensive, risky, irreversible, and not evidence-based. There is a need
      for a conservative reversible noninvasive treatment that is quick, easy,
      relatively inexpensive, long acting, and effective. Botulinum toxin, a natural
      protein, is one of the most potent biological substances known. Masticatory
      muscle relaxation can be reliably achieved by injecting measured doses of
      botulinum toxin into specific sites in the major muscles of mastication. A
      reduction in dystonia and pain with optimization of function is easily achievable
      with a site- and dose-specific injection protocol. The use of botulinum toxin
      offers the dentist an extremely effective tool to add to the armamentarium for
      treating conditions that derive from masticatory and other pericranial muscular
      conditions, and offers the general dentist who is not an expert in gnathology and
      occlusion a safe, effective treatment for controlling the symptoms of masticatory
      muscle hypertonicity.

PMID- 16438263
TI  - Minor oral surgery in anticoagulated patients: local measures alone are
      sufficient for haemostasis.
AB  - Minor oral surgery in warfarinized patients can be performed without stopping or
      altering the dose of the drug. Thirty patients underwent various types of oral
      surgical procedures without interruption of their anticoagulant therapy and their
      therapeutic international normalized ratio maintained. Local measures such as
      pressure, packing the sockets with oxidized regenerated cellulose, and suturing
      were applied. In some patients, tranexamic acid mouthwashes were prescribed to
      further enhance haemostasis. Four patients had minimal postoperative bleeding in
      the form of bloodstained saliva, which lasted for 24 hours. This study highlights
      the importance of local measures in controlling postoperative bleeding in
      warfarinized patients undergoing minor oral surgical procedures.

PMID- 16438264
TI  - A survey of perceived stress among undergraduate dental students in Universiti
      Kebangsaan Malaysia.
AB  - The objectives of this study were to determine the sources of stress among
      undergraduate dental students, and to compare the sources of stress among the 5
      years of undergraduate study, between gender, and with other studies done
      elsewhere. A total of 325 students across the 5 academic years (88.8% response
      rate) of the Faculty of Dentistry, Universiti Kebangsaan Malaysia, completed the
      modified Dental Environment Stress questionnaire. All respondents reported that
      they experienced some form of stress. The preclinical students reported that
      examinations and fear of failure caused the most stress. The main stressor for
      clinical students was clinical training, particularly factors relating to meeting
      clinical requirements. Female students perceived more stress generally than male
      students. However, male students were more stressed when faced with factors
      related to clinical training.

PMID- 16438265
TI  - Patient satisfaction with fixed partial dentures: a 5-year retrospective study.
AB  - OBJECTIVE: The aims of this retrospective study were to evaluate patient
      satisfaction with fixed partial dentures (FPDs) 5-8 years following placement and
      to assess their awareness of oral health and oral hygiene practices using a
      survey questionnaire. METHODS: The questionnaire consisted of 15 statements on
      patients' subjective perception of treatment with FPDs. Patients' perceptions of
      clinical outcome in terms of aesthetics, masticatory efficiency, speech, and
      comfort of the FPD were scored on a 4-point ordinal scale. Another group of
      questions looked into patients' attitudes regarding oral hygiene measures; these
      responses were measured on a binary scale. A third group of questions determined
      patients' awareness of bleeding gingivae, and the final group of questions
      assessed if patients' expectations had been met, willingness to undergo the same
      treatment again and recommend it to others. RESULTS: Eighty-five patients with 99
      FPDs, treated between 5 and 8 years previously (mean, 6.1 years; median, 6.2
      years), participated in the study. Mean follow-up time was 6.1 years. There were
      87.9% of FPDs that were 3-4 units in design and 44% included anterior teeth. The
      5-year survival of the FPDs was 92.3%. Patient satisfaction with the functional
      aspects of the FPDs was generally very high; 95% were definitely or somewhat
      satisfied with the aesthetic appearance, 96% with chewing comfort, and 100% with
      the ability to speak normally. Ninety-one percent found the costs to be
      definitely or somewhat reasonable. Ninety-nine percent felt that the treatment
      had definitely or somewhat turned out as they had expected, 95% would definitely
      or somewhat be willing to recommend the same treatment to friends, and 92% would
      undergo the same treatment again. Fifty-six percent of patients reported using
      some form of interdental aid and 86% reported being able to clean their
      prostheses without problems. However, 35% reported some bleeding around their
      prostheses during cleaning, and 74-78% of patients felt that bleeding around
      natural teeth and bridges during cleaning was only a minor problem or not a
      problem. CONCLUSION: More than 90% of patients were satisfied with having missing
      teeth replaced with FPDs from a functional and aesthetic point of view. Costs
      were considered to be reasonable by the majority of patients and most would
      undergo the same treatment again and also recommend the treatment to others. Only
      about half of patients used some form of interdental cleaning and most were
      unaware of the significance of bleeding around the gingiva of natural teeth and
      FPDs.

PMID- 16438266
TI  - Rehabilitation of the edentulous mandible with implant-supported overdentures
      using prefabricated telescopic copings.
AB  - The rehabilitation of edentulous mandibles by means of implant-retained
      overdentures is well established and documented. The majority of systems that
      adopt this approach, however, require a high level of laboratory support. Two
      cases are presented describing the use of prefabricated copings to significantly
      reduce the dependence on complex laboratory procedures. One case features
      immediate loading while the other describes delayed loading after second-stage
      surgery, further illustrating the versatility of the system.

PMID- 16438267
TI  - Bisphosphonate-related osteonecrosis of the jaws.
AB  - The purpose of this paper is to highlight an emerging phenomenon of osteonecrosis
      of the jaws that occurs in some patients who are on long-term bisphosphonate
      therapy. The condition can appear spontaneously or as a result of trauma, and is
      difficult to treat. Dental surgeons must be aware of patients who are at risk and
      institute appropriate preventive care. It is also important to recognize the
      condition when it does appear and refer appropriately. We present the first local
      case series of the condition showing varied clinical presentations and
      treatments.

PMID- 16438268
TI  - The killing field of Khao Lak: forensic odontology in Thailand tsunami victim
      identification.
AB  - Forensic odontology is the science of dental identification. This paper describes
      the contribution of forensic odontology to tsunami victim identification in
      Thailand, with particular reference to the Singaporean victims. Thirteen
      Singaporeans were reported missing in Phuket following the Indian ocean tsunami
      on 26 December 2004. To date, 10 victims have been found and identified, eight of
      whom were identified by dental records. The author travelled twice to southern
      Thailand and spent 5 weeks there. First, in December 2004 as part of a Singapore
      Police Force Disaster Victim Identification team deployed in Khao Lak, and later
      in July 2005 at the Thai Tsunami Victim Identification Information Management
      Centre in Phuket.

PMID- 16438269
TI  - Diabetes mellitus: are adipocytes passive depot of energy or have any role in
      energy balance?

PMID- 16438270
TI  - Factors determining outcome of acute renal failure patients.
AB  - OBJECTIVE: Acute Renal Failure (ARF) is a common medical problem. Delay in
      diagnosis is associated with increased mortality. Variety of conditions can lead
      to ARF. Many factors can influence the outcome of ARF. This study was done to
      find the predictive factors related to outcome of ARF. METHODS: One hundred adult
      patients of acute renal failure admitted to Ziauddin Hospital were studied.
      Certain factors related to outcome of ARF were identified and analyzed. RESULTS:
      Among such factors oliguria, levels of urea, creatinine and potassium were found
      significant poor prognostic predictors on univariate analysis as far as outcome
      of treatment modality is concerned. The multivariate analysis revealed that the
      presence of oliguria is the only significant independent predictor (P<0.001) for
      good outcome with dialysis. CONCLUSION: Oliguria was found to be the major
      predictor of non recovery of renal function.

PMID- 16438271
TI  - Comparison of two surveys of head injured patients presenting during a calendar
      year to an urban medical centre 32 years apart.
AB  - OBJECTIVE: To study the patients presenting with head injuries to a tertiary
      hospital in Karachi during the year 2003. METHODS: During the calendar year 2003,
      a cross-sectional study was conducted of all patients presenting to the casualty
      department of Jinnah Postgraduate Medical Centre (JPMC) with head injury.
      Personal information was collected from the patient's attendants at presentation
      or later if the patient had been brought in by the emergency services as an
      unknown person. The circumstances of the injury were similarly established and
      the clinical features documented. RESULTS: During the year 2003, a total of 3008
      patients reported to the emergency room of JPMC. Of these 67% were males and the
      majority of the reporting patients (48%) had suffered their head injury in falls
      from a height. However, when considering the seriously injured patients
      warranting admission to the neurosurgery unit, road traffic injuries predominated
      (54%) and the age distribution was weighed towards an older age group with 70%
      being above the age of 20 years and mainly in the economically active 4th decade
      of life. One hundred and fifty four patients died for a mortality rate of 5% in
      the entire series of 3008 patients and 25% of the 623 admitted patients.
      CONCLUSION: The experience of head injuries reporting to our centre in two
      calendar years, 33 years apart, suggests that this attention to the crisis of
      death and disability occurring on roads is necessary.

PMID- 16438272
TI  - Validity of frozen section in the diagnosis of breast lumps: 5 years experience
      at the Aga Khan University Hospital.
AB  - OBJECTIVE: To determine the accuracy of frozen section in the diagnosis of breast
      lump. METHODS: Frozen section diagnosis given in consecutive breast biopsies
      performed in 5 years in our laboratory was evaluated against the final pathology
      report of permanent sections. RESULTS: The Aga Khan University Hospital Lab
      receives more than 400 cases per year for frozen section. Three hundred and
      nineteen consecutive frozen sections of breast lumps examined from 1999-2003 were
      considered for analysis. Age of patients ranged between 22 and 90 years (mean age
      49 years). In 316 cases (99%) there was no difference between the frozen section
      diagnosis and the final diagnosis. Three cases (0.94%) were incorrect; 2 cases
      (0.62%) were false positive. One case was false negative (0.31%). In 7 cases
      (2.19%), frozen section diagnosis was deferred to permanent sections. Frozen
      section diagnostic accuracy was 99%. Sensitivity and specificity was 99.3% and
      93% respectively. Positive predictive value and negative predictive values of
      frozen section were 96.6% and 99.3% respectively. CONCLUSION: High accuracy of
      the frozen-section diagnosis in the breast lumps was confirmed in our study

PMID- 16438273
TI  - Fixation of bilateral pelvic osteotomies with external fixator in exstrophy
      bladder complex.
AB  - OBJECTIVE: To present the early results of pelvic osteotomies performed for
      repair of exstrophy bladder. METHODS: Five cases of exstrophy bladder were
      treated with closure following bilateral iliac osteotomies. Three patients
      underwent closure of pubic symphysis diastasis by use of external fixator, one by
      screws and cerclage wires, and one by use of K-wires and suture. The patients
      were followed up by the pediatric urologist and orthopedic surgeon. RESULTS: All
      patients achieved a closure of diastasis and a tension free repair after the
      index surgery. The average follow-up was 3.6 years with range of 4 months to 6
      years. All osteotomies healed within two months and had closure of the diastasis,
      except one which had a partial failure with loss of 50% correction. No patient
      had any wound dehiscence or breakdown of the bladder repair. Preoperative mean
      diastasis of symphysis pubis was 6 cm (range; 4.5 cm to 7 cm) and post operative
      mean diastasis was 3.5 cm with the range of 2.5 cm to 4 cm at 12 months follow
      up. All patients achieved urinary continence post operatively and were passing
      urine per-urethra with satisfactory urinary control as followed-up with the
      pediatric urologists. CONCLUSION: Bilateral iliac osteotomies and use of external
      fixator in our series was found to be helpful in achieving a tension free closure
      and preventing dehiscence of the repair.

PMID- 16438274
TI  - Speech results with tracheoesophageal voice prosthesis after total laryngectomy.
AB  - OBJECTIVE: To assess the success rate of tracheoesophageal voice prosthesis as
      the primary mode of voice rehabilitation in patients after total laryngectomy.
      METHODS: Medical record files of 35 patients subjected to total laryngectomy were
      reviewed for determining success or failure of the voice prosthesis. The
      indicators used were quality of speech and utility of the device. Subsequent
      complications that developed were also assessed. In addition other factors taken
      into consideration were pharyngeal myotomy, use of radiation, and timing of
      replacement. All thirty five patients (n=35) had prosthesis placed at the time of
      laryngectomy. RESULTS: The success rate at one month and four months follow up
      was 85.18%. Of note, 3 patients were lost to follow-up, 3 patients died of
      disease and 2 had recurrence of disease. CONCLUSION: Our results confirm the
      effectiveness, longevity and safety of the tracheoesophageal voice prosthesis for
      speech rehabilitation following total laryngectomy.

PMID- 16438275
TI  - Does malaria during pregnancy affect the newborn?
AB  - OBJECTIVE: To investigate the effect of malarial infection during pregnancy on
      the newborn. METHODS: A retrospective cohort study was conducted at The Aga Khan
      University Hospital (AKUH), Karachi, using in-patient hospital records over an 11
      year period from 1988 to 1999. The incidence of preterm delivery, low birth
      weight (LBW) and intrauterine growth retardation (IUGR) in 29 pregnant women with
      malaria, was compared with that in 66 selected pregnant women without malaria,
      who delivered at the AKUH during the same time period. RESULTS: Pregnant women
      with malaria had a 3.1 times greater risk of preterm labor (p=0.14). They were
      more likely to be anaemic compared to women without malaria (RR=2.9, 95% CI=1.6
      5.4) and had a significantly lower mean haemoglobin level (p=0.0001). Maternal
      malaria was significantly associated with LBW babies (p=0.001). The mean birth
      weight of infants born to pregnant women with malaria was 461 g less (p=0.0005).
      No significant association was, however, found between malarial infection during
      pregnancy and IUGR (p=0.33). CONCLUSION: Malarial infection during pregnancy is
      associated with poor maternal and fetal outcome. It is significantly associated
      with maternal anaemia and LBW infants. Appropriate measures must, therefore, be
      taken to prevent malaria during pregnancy, especially in endemic areas.

PMID- 16438276
TI  - Premenstrual syndrome: frequency and severity in young college girls.
AB  - OBJECTIVES: To find out the frequency of premenstrual syndrome (PMS) in young
      college girls and to describe the severity of emotional, physical and behavioural
      symptoms. METHODS: An observational study was conducted at the Khyber Medical
      College, Peshawar by convenient sampling on 384 young girls. Data was collected
      over two cycles by filling a 29 items shortened premenstrual assessment form
      based on Moos Menstrual Distress Questionnaire after taking consent from medical
      students. Results were given according to both criteria i.e. ICD-10 and DSM-IV.
      RESULTS: The frequency of premenstrual syndrome was 53% according to ICD-10
      criteria, among which 42% was mild, 18.2% moderate and 31.7% severe. A total of
      64 girls (18.2%) met the DSM-IV criteria for severe PMS or Premenstrual Dysphoric
      disorder (PMDD). The order of frequency of symptoms occurring in PMS was general
      body discomfort, anxiety, backache, fatigue and depression. Most frequently
      reported symptoms in PMDD group were anger, anxiety, stress, depression, fatigue
      and general body discomfort. CONCLUSION: Premenstrual syndrome is a common
      problem in young girls. Doctors should adopt comprehensive measures to reduce its
      incidence and improve the quality of life in the affected.

PMID- 16438277
TI  - Association of literacy of mothers with malnutrition among children under three
      years of age in rural area of district Malir, Karachi.
AB  - OBJECTIVE: To determine the association of literacy of mothers with malnutrition
      among children under three years of age in rural area of district Malir, Karachi.
      METHODS: A cross-sectional study was conducted on four hundred children under
      three years of age, residing in the rural area of district Malir, Karachi. The
      selection of the children was irrespective of gender, ethnicity and religion.
      RESULTS: Three hundred nineteen mothers (79.75%) were illiterate and 81 (20.25%)
      were literate. In the latter group, three mothers could read or write only, 38
      had primary, 10 middle, 15 matric, 12 intermediate and 3 mothers had education up
      to graduate level. Maximum malnutrition regarding stunting (40.75%) was seen in
      children who's mothers were illiterate and maximum underweight (57.89%) was seen
      in children who's mothers had education up to primary level and maximum wasting
      (33.33%) was seen in children who's mothers (only 3 mothers out of 400) were
      graduates. There was a significant difference regarding underweight between the
      children who's mothers were illiterate or had education up to primary level in
      comparison to the children who's mothers had education to more than primary level
      (P<0.016), but in significant difference regarding stunting and wasting was
      found. Overall a total of 217 (54.25%) children were underweight, 156 (39%) were
      stunted and 86 (21.5%), had wasting. CONCLUSION: Mother's literacy status has a
      definite association with the malnutrition of the children <3 years of age
      regarding underweight. In order to combat this an uplift of mother's literacy
      status is badly needed especially in the rural areas.

PMID- 16438278
TI  - The role of human papilloma virus (HPV) in the aetiology of cervical cancer.

PMID- 16438279
TI  - Retrospective review of the use of Swan Ganz catheters in our intensive care unit
      (ICU): a short report.
AB  - The widespread and often 'misuse' of the Swan Ganz (SG) or Pulmonary artery
      catheter has often been seen in intensive care patients. The objective of this
      preliminary review was to observe the trends and possibly formulate an
      association with outcome of the use of SG catheters as well as to determine the
      frequency of use and possible complications. The chart review of ten patients was
      carried out for the months of January and February 2004 in a retrospective
      manner. The incidence of SG catheter insertion was 12% per month on average. Nine
      out of 10 patients received the SG catheters for 'fluid management'; and 1 for
      'haemodynamic instability'. Eight out of 10 patients expired and average length
      of stay was 9 days. There were no complications recorded. The cause of death in
      all patients was 'severe sepsis'. The overwhelming majority of patients who
      received these catheters expired at the end of their stay.

PMID- 16438280
TI  - Cephalosporin resistant Shigella flexneri from a clinical isolate--a rare
      finding.
AB  - Shigellosis is an important public health problem, especially in developing
      countries. Antibiotic treatment of dysentery aimed at resolving diarrhea or
      reducing its duration, and to prevent transmission to other close contacts.
      Isolates with resistance to first line drugs have been reported throughout world,
      third generation cephalosporins and quinolones are mainstay of treatment.
      Shigella flexneri resistant to third generation cephalosporins in a clinical
      isolate is a rare finding, and this has been reported for the first time in
      Pakistan.

PMID- 16438281
TI  - Primary carcinoid tumour of the testis.
AB  - A left radical orchidectomy was performed on a 32-year-old man presenting with a
      testicular mass. Histology revealed a tumour comprising of cells with monotonous
      nuclei and granular cytoplasm arranged in an insular pattern. Immunohistochemical
      expression for NSE, synaptophysin and chromogranin A were positive. No
      teratomatous elements were seen. Postoperatively, a staging CT and an octreotide
      scan were normal. Urinary 5-HIAA levels were not elevated. Based on these
      investigations the tumour was diagnosed as a pure primary carcinoid tumour of the
      testis. The patient has been followed up for 3 years with no evidence of
      recurrence.

PMID- 16438282
TI  - Frequency of irregular red cell alloantibodies in patients with thalassemia
      major: a bicenter study.
AB  - OBJECTIVE: To provide frequency and distribution pattern of various types of
      irregular red cell alloantibodies in patients with thalassemia major. METHODS:
      This is a descriptive study conducted at two centers from January to December
      2001. Purposive sampling was done and all patients diagnosed to have thalassemia
      major were included in the study. Antibody identification was carried out on
      serum employing commercial two-cell panel using standardized blood bank methods.
      If patients were found to have an irregular red cell alloantibody then the
      antibody identification was performed using 16 panel cells. RESULTS: A total of
      ninety-seven patients were included in the study. Fifty-three patients were males
      and 44 females. Mean age was 10.6 years. Irregular red cell alloantibodies were
      found in 9 (9.2%). Mean age of patients who developed red cell alloantibody was
      11.9 years. Three (33.3%) patients developed anti-K while two (22.2%) had non
      specific antibody. One patient each developed anti-D (11.1%) and anti-E (11.1%).
      Two had anti-D (11.1%) and anti-C while the other one (11.1%) developed anti-E
      and anti-K. CONCLUSION: We concluded that there is relatively high rate of
      alloimmunization in our set of patients when compared to data from our region. We
      also suggest that red cell alloimmunization should not be overlooked in patients
      receiving regular blood transfusions.

PMID- 16438283
TI  - A case of transient diabetes insipidus following cardiopulmonary bypass.
AB  - Cardiopulmonary bypass surgery has been linked with a number of postoperative
      complications. One of the frequently reported physiological alterations is the
      relative diuresis seen in the immediate post-op period. Rarely reported though is
      the development of full-blown diabetes insipidus in such patients. The etiology
      is unknown and has only been hypothesized in the past. We present the clinical
      course of a 54 year old male who developed transient diabetes insipidus post
      bypass surgery with subsequent recovery following exogenous vasopressin
      administration. The physiological alteration leading to the development of
      diabetes insipidus in a small fraction of bypass patients remains unknown. We
      propose that the variation in natriuretic peptide levels in the post-bypass
      period could account for the transient event.

PMID- 16438284
TI  - Type 2 diabetes and risk of osteoporosis.

PMID- 16438285
TI  - Acrylamide in food: the discovery and its implications: a historical perspective.
AB  - The unexpected finding that humans are regularly exposed to relatively high doses
      of acrylamide (AA) through normal consumption of cooked food was a result of
      systematic research and relevant developments in methodology over decades, as
      well as a chain of certain coincidences. The present paper describes the
      scientific approach, investigations and events leading to the discovery of the
      formation of AA during cooking of foods. In addition, related issues concerning
      assessment, communication and management of cancer risks and associated ethical
      questions raised by the finding of the presence of AA in foods will be discussed.

PMID- 16438286
TI  - Acrylamide neurotoxicity: neurological, morhological and molecular endpoints in
      animal models.
AB  - Acrylamide (AA) monomer is used in numerous chemical industries and is a
      contaminant in potato- and grain-based foods prepared at high temperatures.
      Although experimental animal studies have implicated carcinogenicity and
      reproductive toxicity as possible consequences of exposure, neurotoxicity is the
      only outcome identified by epidemiological studies of occupationally exposed
      human populations. Neurotoxicity in both humans and laboratory animals is
      characterized by ataxia and distal skeletal muscle weakness. Early
      neuropathological studies suggested that AA neurotoxicity was mediated by distal
      axon degeneration. However, more recent electrophysiological and quantitative
      morphometric analyses have identified nerve terminals as primary sites of AA
      action. A resulting defect in neurotransmitter release appears to be the
      pathophysiological basis of the developing neurotoxicity. Corresponding
      mechanistic research suggests that AA impairs release by adducting cysteine
      residues on functionally important presynaptic proteins. In this publication we
      provide an overview of recent advances in AA research. This includes a discussion
      of the cumulative nature of AA neurotoxicity and the putative sites and molecular
      mechanisms of action.

PMID- 16438287
TI  - The role of epidemiology in understanding the relationship between dietary
      acrylamide and cancer risk in humans.
AB  - Since April 2002, when the Swedish National Food Administration first reported
      its finding of elevated levels of the substance acrylamide in commonly consumed
      foods (Swedish National Food Administration, 2002), there has been considerable
      debate about the health effects of dietary exposure to acrylamide. In particular,
      researchers have speculated on whether the amount of acrylamide consumed through
      the typical diet could increase the risk of cancer in humans. In this paper, we
      review the epidemiological data to date examining dietary acrylamide in relation
      to cancer risk. We highlight the strengths and limitations of using epidemiology
      to address this public health question. Finally, we provide an overview of future
      directions of epidemiological research on the health effects of dietary
      acrylamide.

PMID- 16438288
TI  - Mechanisms of acrylamide induced rodent carcinogenesis.
AB  - Acrylamide is a monomer of polyacrylamide, used in biochemistry, in paper
      manufacture, in water treatment, and as a soil stabilizer. The monomer can cause
      several toxic effects and has the potential for human exposure either through the
      environment or from occupational exposure. Recently, additional concern for the
      potential toxicity of acrylamide in humans has arisen with the finding of
      acrylamide formation in some processed foods. It has been established that
      following chronic exposure, rats exhibited an increase in the incidence of
      adrenal pheochromocytomas, testicular mesotheliomas, thyroid adenomas and mammary
      neoplasms in F344 rats. This has raised increased concerns regarding the
      carcinogenic risk to humans from acrylamide exposure. Studies examining the DNA
      reactivity of acrylamide have been performed and have had differing results. The
      tissue and organ pattern of neoplastic development seen in the rat following
      acrylamide exposure is not consistent with that seen with other strictly DNA
      reactive carcinogens. Based on the pattern of neoplastic development, it appears
      that acrylamide is targeting endocrine sensitive tissues. In the current
      monograph, studies on the effect of acrylamide on DNA reactivity and on altered
      cell growth in the target tissues in the rat are reported. DNA synthesis was
      examined in F344 rats treated with acrylamide (0, 2, or 15 mg/kg/day) for 7, 14,
      or 28 days. Acrylamide increased DNA synthesis in the target tissues (thyroid,
      testicular mesothelium, adrenal medulla) at all doses and time points examined.
      In contrast, in a non-target tissue (liver), no increase in DNA synthesis was
      seen. Examination of DNA damage using single cell gel electrophoresis (the Comet
      assay) showed an increase in DNA damage in the target tissues, but not in non
      target tissue (liver). In addition, a cellular transformation model, (the Syrian
      Hamster Embryo (SHE) cell morphological transformation model), was used to
      examine potential mechanisms for the observed carcinogenicity of acrylamide. SHE
      cell studies showed that glutathione (GSH) modulation by acrylamide was important
      in the cell transformation process. Treatment with a sulfhydryl donor compound
      (NAC) reduced acrylamide transformation while depletion of GSH (BSO) resulted in
      an enhancement of transformation. In summary, acrylamide caused both an increase
      in DNA synthesis and DNA damage in mammalian tissues and cells suggesting that
      DNA reactivity and cell proliferation, in concert, may contribute to the observed
      acrylamide-induced carcinogenicity in the rat and has implication on the possible
      risk for human neoplasm development.

PMID- 16438289
TI  - Exposure to acrylamide: placing exposure in context.
AB  - This paper attempts to assess possible risks that may result from human exposure
      to dietary intake of acrylamide.

PMID- 16438290
TI  - Acrylamide and glycidamide: approach towards risk assessment based on biomarker
      guided dosimetry of genotoxic/mutagenic effects in human blood.
AB  - Acrylamide (AA) is a carcinogen as demonstrated in animal experiments, but the
      relevance for the human situation is still unclear. AA and its metabolite
      glycidamide (GA) react with nucleophilic regions in biomolecules. However,
      whereas AA and GA react with proteins, DNA adducts are exclusively formed by GA
      under conditions simulating in vivo situations. For risk assessment it is of
      particular interest to elucidate whether AA or GA within the plasma concentration
      range resulting from food intake are "quenched" by preferential reaction with non
      critical blood constituents or whether DNA in lymphocytes is damaged
      concomitantly under such conditions. To address this question dose- and time
      dependent induction of hemoglobin (Hb) adducts as well as genotoxic and mutagenic
      effects by AA or GA were studied in human blood as a model system.

PMID- 16438291
TI  - Pilot study on the impact of potato chips consumption on biomarkers of acrylamide
      exposure.
AB  - Food is assumed to be one major source of acrylamide exposure in the general
      population. Acrylamide exposure is usually assessed by measuring hemoglobin
      adducts of acrylamide and its primary metabolite glycidamide as biomarkers.
      Little is known about the impact of acrylamide in food on biomarkers of
      acrylamide exposure. Therefore, CDC is conducting a feeding study to investigate
      the effect of consumption of endogenous acrylamide in food on biomarkers of
      acrylamide exposure. As part of this study, we performed a pilot study to obtain
      further information on the magnitude of the changes in biomarker levels after
      consumption of high amounts of potato chips (21 ounces) over a short period of
      time (1 week) in non-smokers. After 1 week, biomarkers levels increased up to 46%
      for acrylamide adducts and 79% for glycidamide adducts. The results indicate that
      changes in biomarker levels due to consumption of potato chips can be detected.
      However, because of the design of this pilot study, the observed magnitude of
      change cannot be. generalized and needs to be confirmed in the main study.

PMID- 16438292
TI  - LC/MS/MS method for the analysis of acrylamide and glycidamide hemoglobin
      adducts.
AB  - Hemoglobin adducts of acrylamide and its primary metabolite, glycidamide are used
      as biomarkers of acrylamide exposure. Several methods for analyzing these
      biomarkers in blood have been described previously. These methods were developed
      to analyze small numbers of samples, not the high sample throughput that is
      needed in population screening. Obtaining data on exposure of the US population
      to acrylamide through food and other sources is important to initiate appropriate
      public health activities. As part of the Centers for Disease Control and
      Prevention biomonitoring activities, we developed a high throughput liquid
      chromatography tandem mass spectrometry (LC/MS/MS) method for hemoglobin adducts
      of acrylamide. The LC/MS/MS method consists of using the Edman reaction and
      isolating the reaction products by protein precipitation and solid-phase
      extraction (SPE). Quantitation is achieved by using stable-isotope labeled
      peptides as internal standards. The method is performed on an automated liquid
      handling and SPE system. It provides good sensitivity in the low-exposure range
      as assessed in pooled samples and enables differentiation between smokers and non
      smokers.

PMID- 16438293
TI  - Comparison of acrylamide metabolism in humans and rodents.
AB  - Acrylamide is metabolized by direct conjugation with glutathione or oxidation to
      glycidamide, which undergo further metabolism and are excreted in urine. In rats
      administered 3 mg/kg 1,2,3-13C3 acrylamide, 59% of the metabolites excreted in
      urine was from acrylamide-glutathione conjugation, whereas 25% and 16% were from
      two glycidamide-derived mercapturic acids. Glycidamide and dihydroxypropionamide
      were not detected at this dose level. The metabolism of acrylamide in humans was
      investigated in a controlled study with IRB approval, in which sterile male
      volunteers were administered 3 mg/kg 1,2,3-13C3 acrylamide orally. Urine was
      collected for 24 h after administration, and metabolites were analyzed by 13C NMR
      spectroscopy. At 24 h, urine contained 34% of the administered dose, and 75% of
      the metabolites were derived from direct conjugation of acrylamide with
      glautathione. Gycidamide, dihydroxypropionamide and one unidentified metabolite
      were also detected in urine. This study indicated differences in the metabolism
      of acrylamide between humans and rodents.

PMID- 16438294
TI  - Kinetic and mechanistic data needs for a human phsiologically based
      pharmacokinetic (PBPK) model for acrylamide: pharmacokinetic model for
      acrylamide.
AB  - A pharmacokinetic (PBPK) model has been developed for acrylamide (AMD) and its
      oxidative metabolite, glycidamide (GLY), in the rat based on available
      information. Despite gaps and limitations to the database, model parameters have
      been estimated to provide a relatively consistent description of the kinetics of
      acrylamide and glycidamide using a single set of values (with minor adjustments
      in some cases). Future kinetic and mechanistic studies will need to focus on the
      collection of key data for refining certain model parameters and for model
      validation, as well as for conducting studies that elucidate the mechanism of
      action. Development of a validated human AMD/GLY PBPK model capable of predicting
      target tissue doses at relevant dietary AMD exposures, in combination with
      expanding data on modes of action, should allow for a substantive improvement in
      the risk assessment of acrylamide in food.

PMID- 16438295
TI  - In vitro studies of the influence of certain enzymes on the detoxification of
      acrylamide and glycidamide in blood.
AB  - Several enzymes involved in the metabolism of xenobiotic substances are
      polymorphic in humans. Inter-individual differences in response to certain
      chemicals, such as acrylamide, as a result of such genetic polymorphisms might
      affect health-risk assessments. Detoxification by, for example, conjugation with
      glutathione (GSH) will decrease the concentration. The dose of the compound and
      enzymes that enhance the conjugation with GSH will increase the detoxification
      rate. The dose of acrylamide or glycidamide has been measured in blood samples
      from individuals with defined genotypes for the glutathione transferases GSTT1
      and GSTM1 after in vitro incubation with these compounds. The results indicate
      that these enzymes have no significant effect on the blood dose, measured as Hb
      adducts over time, after exposure to acrylamide or glycidamide.

PMID- 16438296
TI  - Biological effects of Maillard browning products that may affect acrylamide
      safety in food: biological effects of Maillard products.
AB  - The heat-induced reaction of amino groups of amino acids, peptides, and proteins
      with carbonyl groups of reducing sugars such as glucose results in the concurrent
      formation of so-called Maillard browning products and acrylamide. For this
      reason, reported studies of adverse biological effects of pure acrylamide may not
      always be directly relevant to acrylamide in processed food, which may contain
      Maillard and other biologically active products. These may either antagonize or
      potentiate the toxicity of acrylamide. To stimulate progress, this paper presents
      an overview of selected reported studies on the antiallergenic/allergenic,
      antibiotic, anticarcinogenic/carcinogenic antimutagenic/mutagenic,
      antioxidative/oxidative, clastogenic (chromosome-damaging), and cytotoxic
      activities of Maillard products, which may adversely or beneficially impact the
      toxicity of acrylamide. The evaluation of biological activities of Maillard
      products and of other biologically active food ingredients suggests that they
      could both enhance and/or ameliorate acrylamide toxicity, especially
      carcinogenicity, but less so neurological or reproductive manifestations. Future
      studies should be directed to differentiate the individual and combined
      toxicological relationships among acrylamide and the Maillard products, define
      individual and combined potencies, and develop means to prevent the formation of
      both acrylamide and the most toxic Maillard products. Such studies should lead to
      safer foods.

PMID- 16438297
TI  - Acrylamide formation in different foods and potential strategies for reduction.
AB  - This paper summarizes the progress made to date on acrylamide research pertaining
      to analytical methods, mechanisms of formation, and mitigation research in the
      major food categories. Initial difficulties with the establishment of reliable
      analytical methods have today in most cases been overcome, but challenges still
      remain in terms of the needs to develop simple and rapid test methods. Several
      researchers have identified that the main pathway of formation of acrylamide in
      foods is linked to the Maillard reaction and in particular the amino acid
      asparagine. Decarboxylation of the resulting Schiff base is a key step, and the
      reaction product may either furnish acrylamide directly or via 3
      aminopropionamide. An alternative proposal is that the corresponding
      decarboxylated Amadori compound may release acrylamide by a beta-elimination
      reaction. Many experimental trials have been conducted in different foods, and a
      number of possible measures identified to relatively lower the amounts of
      acrylamide in food. The validity of laboratory trials must, however, be assessed
      under actual food processing conditions. Some progress in relatively lowering
      acrylamide in certain food categories has been achieved, but can at this stage be
      considered marginal. However, any options that are chosen to reduce acrylamide
      must be technologically feasible and also not negatively impact the quality and
      safety of the final product.

PMID- 16438298
TI  - Mechanisms of acrylamide formation: Maillard-induced transformation of
      asparagine.
AB  - The formation of acrylamide (AA) from L-asparagine was studied in Maillard model
      systems under pyrolysis conditions. While the early Maillard intermediate N
      glucosylasparagine generated approximately 2.4 mmol/mol AA, the Amadori compound
      was a less efficient precursor (0.1 mmol/mol). Reaction with alpha-dicarbonyls
      resulted in relatively low AA amounts (0.2-0.5 mmol/mol), suggesting that the
      Strecker aldehyde pathway is of limited relevance. Similarly, the Strecker
      alcohol 3-hydroxypropanamide generated low amounts of AA (0.2 mmol/mol). On the
      other hand, hydroxyacetone afforded more than 4 mmol/mol AA, indicating that
      alpha-hydroxycarbonyls are more efficient than alpha-dicarbonyls in transforming
      asparagine into AA. The experimental results are consistent with the reaction
      mechanism proposed, i.e. (i) Strecker-type degradation of the Schiff base leading
      to azomethine ylides, followed by (ii) beta-elimination of the decarboxylated
      Amadori compound to release AA. The functional group in beta-position on both
      sides of the nitrogen atom is crucial. Rearrangement of the azomethine ylide to
      the decarboxylated Amadori compound is the key step, which is favored if the
      carbonyl moiety contains a hydroxyl group in beta-position to the N-atom. The
      beta-elimination step in the amino acid moiety was demonstrated by reacting under
      pyrolysis conditions decarboxylated model Amadori compounds obtained by
      synthesis.

PMID- 16438299
TI  - Mechanistic pathways of formation of acrylamide from different amino acids.
AB  - Studies on model systems of amino acids and sugars have indicated that acrylamide
      can be generated from asparagine or from amino acids that can produce acrylic
      acid either directly such as beta-alanine, aspartic acid and carnosine or
      indirectly such as cysteine and serine. The main pathway specifically involves
      asparagine and produces acrylamide directly after a sugar-assisted
      decarboxylation and 1,2-elimination steps and the second non-specific pathway
      involves the initial formation of acrylic acid from different sources and its
      subsequent interaction with ammonia to produce acrylamide. Aspartic acid, beta
      alanine and carnosine were found to follow acrylic acid pathway. Labeling studies
      with [13C-4]aspartic acid have confirmed the occurrence in aspartic acid model
      system, of a previously proposed sugar-assisted decarboxylation mechanism
      identified in asparagine model systems. In addition, creatine was found to be a
      good source of methylamine and was responsible for the formation of N
      methylacrylamide in model systems through acrylic acid pathway. Furthermore,
      certain amino acids such as serine and cysteine were found to generate pyruvic
      acid that can be converted into acrylic acid and generate acrylamide when reacted
      with ammonia.

PMID- 16438300
TI  - New aspects on the formation and analysis of acrylamide.
AB  - The effectiveness of different compounds in the generation of acrylamide (AA)
      from asparagine, was determined by reacting asparagine with mono-, di- and
      polysaccharides, as well as four different oxo-compounds known to be involved in
      carbohydrate metabolism/degradation. Quantitation of AA formed either under
      aqueous conditions or in low water model systems revealed glucose and 2
      oxopropionic acid as the most effective compounds in AA generation, when reacted
      in model systems with a low water content (about 1 mol-% yield). Interestingly,
      heating of asparagine in the presence of 2-oxopropionic acid generated quite high
      amounts of 3-aminopropionamide (3-APA), which itself effectively generated AA
      upon heating in aqueous solution, as well as in low water systems. Because this
      is the first report on amounts of 3-APA generated by Maillard-type reactions, the
      general role of 3-APA as key intermediate in AA formation is discussed in detail.
      In addition, first results on the development and application of an
      HPLC/fluorescence method for AA quantitation are presented.

PMID- 16438301
TI  - Formation of acrylamide from lipids.
AB  - Heating amino acids with dietary oils or animal fats at elevated temperatures
      produced various amounts of acrylamide. The amount of acrylamide formation
      corresponded to the degree of unsaturation of the oils and animal fats. The
      decreasing order of acrylamide formation from dietary oils or animal fats with
      asparagine was sardine oil (642 microg/g asparagine) > cod liver oil (435.4
      microg/g) > soybean oil (135.8 microg/g) > corn oil (80.7 microg/g) > olive oil
      (73.6 microg/g) > canola oil (70.7 microg/g) > corn oil (62.1 microg/g) > beef
      fat (59.3 microg/g) > lard (36.0 microg/g). Three-carbon unit compounds such as
      acrylic acid and acrolein, which are formed from lipids by oxidation also
      produced acrylamide by heat treatment with amino acids, in particular with
      asparagine. The results of the present study suggest that acrylamide forms in
      asparagine-rich foods during deep fat frying in the absence reducing sugars.

PMID- 16438302
TI  - Kinetic models as a route to control acrylamide formation in food.
AB  - A kinetic model for the formation of acrylamide in potato, rye and wheat products
      has been derived, and kinetic parameters calculated for potato by multi-response
      modeling of reducing sugar (glucose and fructose), amino acid, asparagine and
      acrylamide concentrations with time. The kinetic mechanism shares, with Maillard
      browning, a rate limiting (probably dicarbonylic) intermediate, and includes
      reaction steps of this intermediate which are competitive with respect to
      acrylamide formation. A pathway representing physical and/or chemical losses of
      acrylamide accounts for the measured reduction of acrylamide yield at long
      reaction times. A mechanistic hypothesis regarding the competing reactions of
      Strecker aldehyde formation and tautomerization followed by beta-elimination to
      give acrylamide, features in the kinetic model and can be used to determine the
      factors which steer the reaction towards acrylamide. A predictive application of
      this model is for 'what-if' experiments to explore the conditions which lead to
      reduced acrylamide yields.

PMID- 16438303
TI  - The effect of cooking on acrylamide and its precursors in potato, wheat and rye.
AB  - The relationship between acrylamide and its precursors, namely free asparagine
      and reducing sugars, was studied in simple cakes made from potato flake,
      wholemeal wheat and wholemeal rye, cooked at 180 degrees C, from 5 to 60 min.
      Between 5 and 20 min, large losses of asparagine, water and total reducing sugars
      were accompanied by large increases in acrylamide, which maximized in all three
      products between 25 and 30 min, followed by a slow linear reduction. Acrylamide
      formation did not occur to any extent until the moisture contents of the cakes
      fell below 5%. A comparison of each type of cake with a commercial product, made
      from the same food material, showed that acrylamide levels in all three
      commercial products were well below the maximum levels in the cooked cakes.

PMID- 16438304
TI  - Determination of acrylamide in various food matrices: evaluation of LC and GC
      mass spectrometric methods.
AB  - Recent concerns surrounding the presence of acrylamide in many types of thermally
      processed food have brought about the need for the development of analytical
      methods suitable for determination of acrylamide in diverse matrices with the
      goals of improving overall confidence in analytical results and better
      understanding of method capabilities. Consequently, the results are presented of
      acrylamide testing in commercially available food products--potato fries, potato
      chips, crispbread, instant coffee, coffee beans, cocoa, chocolate and peanut
      butter, obtained by using the same sample extract. The results obtained by using
      LC-MS/MS, GC/MS (El), GC/HRMS (El)--with or without derivatization--and the use
      of different analytical columns, are discussed and compared with respect to
      matrix borne interferences, detection limits and method complexities.

PMID- 16438305
TI  - Some analytical factors affecting measured levels of acrylamide in food products.
AB  - Acrylamide in food is normally measured as "free water-soluble acrylamide".
      However, it is shown that certain extraction techniques, like extraction as for
      dietary fibre or at high pH can affect the result. This has to be accounted for,
      particularly in exposure assessment and in studies of bioavailability and, in the
      long run, the health risk assessment.

PMID- 16438306
TI  - Analysis of acrylamide in food: dedicated to Professor Dr. Werner Baltes.
AB  - Since the first discovery of the presence of acrylamide in a variety of food
      products in April 2002, numerous methods have been developed to determine the
      acrylamide monomer in heat-treated carbohydrate-rich food. These detection
      methods are mainly MS-based, coupled with a chromatographic step using LC or GC.
      The Food Chemistry Institute (LCI) of the Association of the German Confectionery
      Industry (BDSI) therefore established a detection method by means of aqueous
      extraction plus a cleaning step and LC-MS/MS detection, making great efforts to
      ensure internal and external validation. Citing potato crisps as an example, we
      will in the following show how the German manufacturing companies have gone to
      great pains to reduce acrylamide levels in their products.

PMID- 16438307
TI  - On line monitoring of acrylamide formation.
AB  - A system to monitor the formation of acrylamide in model systems and from real
      food products under controlled conditions of temperature, time and moisture
      content has been developed. By humidifying the gas that flows through the sample,
      some control over moisture content can be affected. Results are presented to show
      the validity and reproducibility of the technique and its ability to deliver
      quantitative data. The effects of different processing conditions on acrylamide
      formation and on the development of color, due to the Maillard reaction, are
      evaluated.

PMID- 16438308
TI  - Factors that influence the acrylamide content of heated foods.
AB  - Our finding that acrylamide is formed during heating of food initiated a range of
      studies on the formation of acrylamide. The present paper summarizes our follow
      up studies on the characterization of parameters that influence the formation and
      degradation of acrylamide in heated foods. The system designed and used for
      studies of the influence of added factors was primarily homogenized potato heated
      in an oven. The net content of acrylamide after heating was examined with regard
      to the following parameters: heating temperature, duration of heating, pH and
      concentrations of various components. Higher temperature (200 degrees C) combined
      with prolonged heating led to reduced levels of acrylamide, due to
      elimination/degradation processes. At certain concentrations, the presence of
      asparagine or monosaccharides (in particular fructose, glucose and
      glyceraldehyde) was found to increase the net content of acrylamide. Addition of
      other free amino acids or a protein-rich food component strongly reduced the
      acrylamide content, probably by promoting competing reactions and/or covalently
      binding of formed acrylamide. The pH-dependence of acrylamide formation exhibited
      a maximum around pH 8; lower pH enhanced elimination and decelerated formation of
      acrylamide. In contrast, the effects of additions of antioxidants or peroxides on
      acrylamide content were not significant. The acrylamide content of heated foods
      is the net result of complex reactions leading to both the formation and
      elimination/degradation of this molecule.

PMID- 16438309
TI  - Model systems for evaluating factors affecting acrylamide formation in deep fried
      foods.
AB  - Simulated food pieces constructed from fiberglass pads (models for French fries
      and chips) were used as carriers for defined aqueous solutions, dispersions of
      test substances and ingredients to evaluate acrylamide formation. The pads were
      loaded with a solution containing asparagine and glucose (10 mM each) plus
      selected reaction modulators before deep fat frying and analysis for acrylamide.
      Data from fiberglass models along with companion sliced potato samples were used
      in developing hypotheses for the mechanisms involved in the suppression of
      acrylamide formation by polyvalent cations, polyanionic compounds, pH, and
      altered food polymer states in fried potato products.

PMID- 16438310
TI  - Controlling acrylamide in French fry and potato chip models and a mathematical
      model of acrylamide formation: acrylamide: acidulants, phytate and calcium.
AB  - We previously reported that in potato chip and French fry models, the formation
      of acrylamide can be reduced by controlling pH during processing steps, either by
      organic (acidulants) or inorganic acids. Use of phytate, a naturally occurring
      chelator, with or without Ca++ (or divalent ions), can reduce acrylamide
      formation in both models. However, since phytate itself is acidic, the question
      remains as to whether the effect of phytate is due to pH alone or to additional
      effects. In the French fry model, the effects on acrylamide formation of pH,
      phytate, and/or Ca++ in various combinations were tested in either blanching or
      soaking (after blanching) steps. All treatments significantly reduced acrylamide
      levels compared to control. Among variables tested, pH may be the single most
      important factor for reducing acrylamide levels, while there were independent
      effects of phytate and/or Ca++ in this French fry model. We also developed a
      mathematical formula to estimate the final concentration of acrylamide in a
      potato chip model, using variables that can affect acrylamide formation: glucose
      and asparagine concentrations, cut potato surface area and shape, cooking
      temperature and time, and other processing conditions.

PMID- 16438311
TI  - Quality related minimization of acrylamide formation--an integrated approach.
AB  - An integrated approach is described with respect to acrylamide minimization in
      heated foodstuffs. All relevant variables have to be considered and the main
      focus is on maintaining the expected product quality. The role of the processes
      at the interface between product and heating medium during processing is
      characterized for the case of frying operations. Examples of parameters
      influencing these processes with respect to minimizing acrylamide and maintaining
      product quality (e.g. brown color) are described. First, the local distribution
      of acrylamide in a French fries type model food was investigated. Lowering water
      activity at the surface of French fries before frying contributes to a reduction
      of acrylamide without lowering product quality. Both pre-drying of the potato
      sticks before frying and an increasing of salt concentration at the product
      surface by coating with a salt solution showed positive effects. Additionally, it
      was demonstrated by simulation that combined effects of these measurements may
      enable a reduction of up to 80% in the acrylamide content.

PMID- 16438312
TI  - Genetic, physiological, and environmental factors affecting acrylamide
      concentration in fried potato products.
AB  - The discovery of acrylamide in processed potato products has brought increased
      interest in the controlling Maillard reaction precursors (reducing sugars and
      amino acids) in potato tubers. Because of their effects on nonenzymatic browning
      of fried potato products, reducing sugars and amino acids have been the focus of
      many potato research and breeding programs. This study focused on changes in
      sugars and amino acids in diploid potatoes selected for their storage qualities
      and their effect on acrylamide formation in the fried product. In addition, a
      second study was performed using cultivated lines that evaluated the effect of
      nitrogen fertilization on amino acid levels in tubers. Glucose, fructose,
      sucrose, and asparagine concentrations in tubers increased upon storage at 2
      degrees C. Glucose and fructose concentrations in the tubers were significantly
      and positively correlated with subsequent acrylamide formation in the products.
      Tuber sucrose and asparagine concentrations did not have an effect on acrylamide
      levels. Acrylamide levels in the products were significantly reduced if tubers
      were preconditioned before being placed in storage at 2 degrees C. Higher rates
      of nitrogen fertilization resulted in increased amino acid concentrations in the
      tubers.

PMID- 16438313
TI  - Acrylamide reduction in processed foods.
AB  - The discovery of the formation of acrylamide in fried and baked foods containing
      high levels of starch and the amino acid asparagine, prompted widespread concern.
      Both processed and home cooked foods are affected and this has led to the
      increased study of variations in cooking and processing conditions to minimize
      formation. While changes in cooking protocols have been in part successful,
      particularly when lower frying and baking temperatures are used, pretreatments to
      reduce levels of acrylamide by prevention of formation or acceleration of
      destruction have been investigated. In this study, a range of pretreatments of
      grilled potato were investigated and compared with surface washing to remove
      asparagine and reducing sugars. Synergies were observed between different
      treatments, and reductions of up to 40% were achieved in a non-optimized system.

PMID- 16438314
TI  - Chemical intervention strategies for substantial suppression of acrylamide
      formation in fried potato products.
AB  - Prototype processes were developed for the substantial suppression of acrylamide
      formation (40-95% compared to untreated controls) in cut surface fried potato
      products using potato chips (crisps) as the primary model. The most efficacious
      procedures employed sequentially both surface preparation and subsequent
      acrylamide precursor complexation and/or competitive inhibition processing steps.
      Surface preparation processing involved either various low-temperature (50-75
      degrees C) aqueous (5-30 min) or ca. 80% ethanol blanch solutions for various
      times (1-5 min) combined with aqueous leaching steps (1-10 min) to reduce
      concentration of acrylamide precursors in the critical frying zone of cut potato
      surfaces. Acrylamide precursor complexation and/or competitive inhibition
      processing strategies included immersion exposure of prepared cut potato surfaces
      to solutions or dispersions of various combinations of either calcium chloride,
      phytic acid, chitosan, sodium acid pyrophosphate, or N-acetylcysteine.

PMID- 16438315
TI  - Acrylamide in Japanese processed foods and factors affecting acrylamide level in
      potato chips and tea.
AB  - Acrylamide concentrations in processed foods sold in Japanese markets were
      analyzed by LC-MS/MS and GC-MS methods. Most potato chips and whole potato-based
      fried snacks showed acrylamide concentration higher than 1000 microg/kg. The
      concentrations in non-whole potato based Japanese snacks, including rice crackers
      and candied sweet potatoes, were less tha. 350 microg/kg. Those in instant
      precooked noodles were less than 100 microg/kg with only one exception. The
      effect of storage condition of potato tubers on acrylamide concentration in
      potato chips after frying was also investigated. Sugar content in the tubers
      increased during cold storage, and the acrylamide concentration increased
      accordingly. The concentrations of asparagine and other amino acids, however, did
      not change during the cold storage. High correlations were observed between the
      acrylamide content in the chips and glucose and fructose contents in the tubers.
      This fact indicated that the limiting factor for acrylamide formation in potato
      chips is reducing sugar, not asparagine content in the tubers. Effects of
      roasting time and temperature on acrylamide concentration in roasted green tea
      are also described.

PMID- 16438316
TI  - The formation of acrylamide in UK cereal products.
AB  - Many bakery products sold in the UK such as crumpets, batch bread and Naan might
      be expected to show high levels of acrylamide because they have strong Maillard
      colours and flavours. However, analysis of commercial products has shown that the
      highest levels of acrylamide are seen in dry biscuit type products. With the
      exception of spiced products such as ginger cake, moist high sugar products (e.g.
      cakes and fruit loaves) show relatively low levels of acrylamide, even in darkly
      browned crusts. This is in contrast to bread where acrylamide levels in excess of
      100 microg/kg are common in the crust region, but are diluted by low levels in
      the crumb. Acrylamide levels in bread are significantly raised by domestic
      toasting, but other products such as crumpets and Naan bread have been found to
      be less sensitive. A mathematical model has been developed (and validated against
      tests on model dough) which shows that once obvious recipe differences are
      allowed for, the key factor limiting acrylamide levels is crust moisture.
      Chemical decay of acrylamide and depletion of amino acids are also limiting
      factors at higher temperatures.

PMID- 16438317
TI  - Factors influencing acrylamide formation in gingerbread.
AB  - The influence of ingredients, additives, and process conditions on the acrylamide
      formation in gingerbread was investigated. The sources for reducing sugars and
      free asparagine were identified and the effect of different baking agents on the
      acrylamide formation was evaluated. Ammonium hydrogencarbonate strongly enhanced
      the acrylamide formation, but its N-atom was not incorporated into acrylamide,
      nor did acrylic acid form acrylamide in gingerbread. Acrylamide concentration and
      browning intensity increased both with baking time and correlated with each
      other. The use of sodium hydrogencarbonate as baking agent reduced the acrylamide
      concentration by more than 60%. Free asparagine was a limiting factor for
      acrylamide formation, but the acrylamide content could also be lowered by
      replacing reducing sugars with sucrose or by adding moderate amounts of organic
      acids. A significant reduction of the acrylamide content in gingerbread can be
      achieved by using sodium hydrogencarbonate as baking agent, minimizing free
      asparagine, and avoiding prolonged baking.

PMID- 16438318
TI  - Effects of consumer food preparation on acrylamide formation.
AB  - Acrylamide is formed in high-carbohydrate foods during high temperature processes
      such as frying, baking, roasting and extrusion. Although acrylamide is known to
      form during industrial processing of food, high levels of the chemical have been
      found in home-cooked foods, mainly potato- and grain-based products. This chapter
      will focus on the effects of cooking conditions (e.g. time/temperature) on
      acrylamide formation in consumer-prepared foods, the use of surface color
      (browning) as an indicator of acrylamide levels in some foods, and methods for
      reducing acrylamide levels in home-prepared foods. As with commercially processed
      foods, acrylamide levels in home-prepared foods tend to increase with cooking
      time and temperature. In experiments conducted at the NCFST, we found that
      acrylamide levels in cooked food depended greatly on the cooking conditions and
      the degree of "doneness", as measured by the level of surface browning. For
      example, French fries fried at 150-190 degrees C for up to 10 min had acrylamide
      levels of 55 to 2130 microg/kg (wet weight), with the highest levels in the most
      processed (highest frying times/temperatures) and the most highly browned fries.
      Similarly, more acrylamide was formed in "dark" toasted bread slices (43.7-610.7
      microg/kg wet weight), than "light" (8.27-217.5 microg/kg) or "medium" (10.9
      213.7 microg/kg) toasted slices. Analysis of the surface color by colorimetry
      indicated that some components of surface color ("a" and "L" values) correlated
      highly with acrylamide levels. This indicates that the degree of surface browning
      could be used as an indicator of acrylamide formation during cooking. Soaking raw
      potato slices in water before frying was effective at reducing acrylamide levels
      in French fries. Additional studies are needed to develop practical methods for
      reducing acrylamide formation in home-prepared foods without changing the
      acceptability of these foods.

PMID- 16438319
TI  - Concerning our ethics. 1911.

PMID- 16438320
TI  - How to be an assertive nurse?

PMID- 16438321
TI  - Last of the big spenders.

PMID- 16438323
TI  - Changing continent.
AB  - The need for better health care in South America is mirrored by the need for
      more, and better trained, nurses. Yet in many countries, nurses continue to have
      poor pay and conditions, as well as low status. Average monthly salaries in South
      America are in the range of 225 pounds to 281 pounds. While nurses typically work
      a 45-hour week, many moonlight to boost their income. Nursing remains largely
      unregulated except for laws which cover all healthcare staff. Low salaries are a
      major incentive for nurses to emigrate or leave the profession altogether.

PMID- 16438324
TI  - Can you help?
AB  - During her time as president of the International Council of Nurses, Christine
      Hancock (pictured opposite) had the opportunity to meet nurses from developing
      countries. While nurse shortages exist in developing countries, many nurses are
      unemployed. HIV/AIDS deaths among nurses can be a bigger problem than nurse
      emigration. Testing and treatment for HIV/AIDS can make nurses role models in
      their communities. Basic sanitation and equipment are often absent.

PMID- 16438325
TI  - International champion. Interview by Jane Salvage.
AB  - While nurses are the first to offer assistance when major disasters strike, it is
      unusual for them to run health charities. But this is exactly what Marion Birch
      has chosen to do in her new role as director of Medact, the London-based global
      health charity.

PMID- 16438326
TI  - Age of innocence.

PMID- 16438327
TI  - Power of knowledge.

PMID- 16438328
TI  - Ditching the dirt.

PMID- 16438329
TI  - Sex: a spiritual goal.

PMID- 16438330
TI  - Impact of the Leading an Empowered Organisation programme.
AB  - AIM: To evaluate the impact of the Leading an Empowered Organisation (LEO)
      programme on the role of grade G nurses and their multidisciplinary colleagues in
      one NHS trust. The LEO programme encourages and promotes leadership skills among
      NHS staff. METHOD: A purposive sample of four grade G nurses, one from each of
      the hospital's four clinical divisions, was included. Each grade G nurse, and his
      or her matron, nominated eight colleagues for interview. The final sample
      comprised four grade G nurses and 32 of their colleagues. Data were analysed
      using the principles of thematic analysis described by Attride-Stirling (2001).
      FINDINGS: The LEO programme improved the grade G nurses' approach to their work
      in relation to competence, communication strategies, problem solving, risk
      taking, leadership and management style. Factors that affected the grade G
      nurses' implementation of the LEO principles included: relationships,
      personality, experience, work context, staffing levels, autonomy and authority.
      CONCLUSION: This study provided insight into how the grade G nurses applied the
      principles of the LEO programme in their daily work. Their ability to apply the
      LEO principles was both restricted and assisted by the culture in which they
      worked. A partnership between theory and practice is needed. This finding has
      implications for the LEO programme and the need for it to be implicit in the
      local working philosophy, that is, the context in which its principles are to be
      used. This is so that the working context and people within it are intimately
      engaged with the individual undertaking the course.

PMID- 16438331
TI  - Communicating effectively with deaf patients.
AB  - This article explores the communication needs of deaf patients who use British
      Sign Language as their first or preferred language. It would appear that these
      needs are not being met, particularly in acute hospital settings. Practical
      advice is provided for nurses to improve the quality of care that deaf patients
      receive.

PMID- 16438332
TI  - Implementing solutions to prevent patient harm.
AB  - This article is the last in this series based on the Seven Steps to Patient
      Safety. Each article analyses one of the seven steps and offers a resource for
      healthcare staff to enhance knowledge, skills and attitudes relating to patient
      safety. This article identifies solutions and actions that healthcare staff can
      take to improve patient safety.

PMID- 16438333
TI  - Nursing and supporting patients with chronic pain.
AB  - Nurses in all settings are likely to be working with patients in chronic pain on
      a regular basis. Although there is much information available about chronic pain,
      there is evidence that nurses find patients with chronic pain difficult to work
      with. This article assists nurses to maintain and develop their practice by
      addressing these issues.

PMID- 16438334
TI  - Care of dying patients.

PMID- 16438335
TI  - Head and hands.

PMID- 16438336
TI  - 'Work worth doing'. Interview by Frances Pickersgill.

PMID- 16438337
TI  - The art of managing difficult people.

PMID- 16438338
TI  - Who guards the guards?

PMID- 16438339
TI  - The secondary transfer of fibres from head hair.
AB  - In this study, the effects of fibre type, hair style, time and fibre persistence
      on the secondary transfer of mask fibres to pillowcases via head hair were
      studied. Volunteers with a range of hair styles, and masks consisting of
      different fibre compositions were used in the study. Fibres from the masks were
      found to transfer from donor subjects to the pillowcases up to 14 nights after
      the mask had been worn. On average, the number of secondarily transferred fibres
      found decreased with time; however, this decrease appeared to be more 'linear' in
      nature, rather than an exponential decay. The greatest degree of secondary
      transfer occurred with cotton, then acrylic, then wool. In a primary
      transfer/persistence experiment with a 50% acrylic/50% wool mask, wool was found
      to persist in the hair more readily than acrylic. The results also showed that
      the greatest degree of secondary transfer occurred via short straight and long
      straight hair, with no clear pattern emerging between medium length hair (both
      straight and curly) and with long curly hair. The implications of these findings
      for the assessment and interpretation of casework are considered along with data
      obtained from related studies.

PMID- 16438340
TI  - Clinical urinalysis of drugs and alcohol in instances of suspected surreptitious
      administration ("spiked drinks").
AB  - Many suspected victims of surreptitious drug and/or alcohol administration may
      present to hospitals or healthcare centres and never come to the attention of
      forensic or law enforcement professionals. Therefore, it is necessary to include
      clinical toxicological findings in order to assess the growing perception that
      instances have become more widespread within society. Between July 2002 and June
      2004, 180 requests were received for toxicological analysis of individuals
      presenting to their GP or hospital following self-reported or suspected
      surreptitious drug administration (e.g. "spiked drink"). There was a rise of 77%
      in the number of requests from 2002-2003 to 2003-2004 which peaked in December of
      each year (most likely due to the increased socialization of people during the
      festive season). Between 2002 and 2004, 34% of patients were male and 66% were
      female with an overall average age of 25 (range 11-73). Following urinary
      analysis using immunoassay and gas chromatography (mass spectrometry, flame
      ionisation detection and nitrogen-phosphorus detection), 59% of cases were
      negative for drugs and alcohol in 2002-2003 and 51% in 2003-2004. Drugs or
      alcohol were detected in 32% of cases in 2002-2003 and in 45% in 2003-2004. Out
      of the 169 cases analysed, ethanol (alcohol) was the most commonly detected
      compound (24% of cases), followed by amphetamines (amphetamine, MDMA, MDA, MDEA-
      11% of cases), cannabinoids (9% of cases), benzodiazepines (temazepam,
      nordiazepam, oxazepam--9% of cases), cocaine (4% of cases), opiates
      (dihydrocodeine, codeine--2% of cases), chlorpheniramine (0.6% of cases),
      ephedrine 0.6% of cases), fluoxetine (0.6% of cases), tramadol (0.6% of cases)
      and zopiclone (0.6% of cases). No gamma-hydroxybutyrate (GHB), gamma
      butyrolactone (GBL) or flunitrazepam was detected in the cases analysed.

PMID- 16438341
TI  - Examination of an altered bar code on a vehicle tax disc.
AB  - Altered vehicle excise licences (tax discs) are regularly submitted for
      questioned document examination in order to reveal the original vehicle details.
      A bar code printed on tax discs permits the electronic storage and transfer of
      vehicle licensing information. In a recent case involving a tax disc on which the
      printed serial number had been partially removed, it was possible to restore and
      manually decode an obliterated bar code. This allowed recovery of the complete
      serial number of the disc and subsequent retrieval of the original entries.

PMID- 16438342
TI  - Isotope ratio mass spectrometry as a tool for forensic investigation (examples
      from recent studies).
AB  - The versatility of isotope ratio mass spectrometry is demonstrated by reference
      to diverse case studies. Variations in the natural isotopic composition of non
      biological, organic materials are compared as a means by which samples may be
      associated or discriminated. These techniques may be used to augment or
      compliment conventional forensic methodologies. delta13C analysis was used to
      demonstrate that different masking tape had been recovered in two, apparently
      similar cases, involving the smuggling of money. Visually similar ecstasy tablets
      were compared by consideration of the delta13C and delta15N composition of MDMA
      extracted from the tablets. Although only a limited number of tablets were
      analysed, the isotopic similarity between two different seizures was sufficient
      to induce a guilty plea from a person suspected of possessing both. A combination
      of delta2H, delta13C, delta15N and delta18O together with GC-MS analyses were
      applied to small samples of seized heroin. Although GC-MS analysis indicated
      differences between the chemical composition of two of the heroin samples,
      isotopic analysis suggested similarities, which were confirmed by further
      delta2H, delta13C and delta18O isotopic analysis of the clingfilm in which the
      samples were wrapped.

PMID- 16438343
TI  - The application of "CrimeLite" to examination of computer components "in situ".
AB  - The authors consider the problem of identifying potential fingerprints and other
      marks in a computer system, having regard for the damage which conventional print
      enhancement techniques may cause. They evaluate a non-invasive method of mark
      location and recommend a new procedure for the handling of digital evidence
      sources which may contain "conventional" evidence.

PMID- 16438345
TI  - Science & justice.

PMID- 16438344
TI  - The analysis and comparison of blue wool fibre populations found at random on
      clothing.
AB  - Fifty-eight garments were taped and searched for mid to dark blue wool fibres.
      These were then removed from the tapings, mounted on slides and examined using a
      high-power microscope (400x). A total of 2,740 blue wool fibres were identified
      and visible range microspectrophotometry (MSP) was performed on them. Three
      hundred independent blue wool populations were identified on 56 of the 58
      garments searched. The lack of control fibres meant the spectral range of each
      population was unknown. The number of populations may have been underestimated by
      grouping together the fibres that had broad single peaks and a lack of
      distinguishing features in the spectra. Although blue wool is considered to be a
      common fibre type, 300 unique spectral shapes were identified by the use of
      microspectrophotometry alone. This demonstrates that the dyes used in the dyeing
      of blue wool are variable. Showing that many different populations of blue wool
      occur on a range of garments should ensure that the forensic scientist does not
      underestimate or understate the strength of evidence in cases where blue wool is
      found. Hopefully this work will enlighten scientists and enable them to also
      assess the true value of their findings when other commonly occurring fibres are
      encountered.

PMID- 16438347
TI  - Tremor in Parkinson's disease patients can be induced by uncontrolled activation
      and uninhibited synchronization of alpha2-motoneuron firing to which alpha1
      motoneuron firing synchronizes.
AB  - With the surface electromyography (sEMG) and the single nerve-fibre action
      potential recording method a mechanism is measured how rhythmic muscle
      contraction and tremor in Parkinson's disease patients is generated. With sEMG it
      could be shown that the tremor started when alpha2-motor units (FR-type)
      spontaneously began to fire synchronizedly oscillatory. Two possibilities of
      alpha2-motor unit synchronization were observed. In one case one alpha2-motor
      unit started to fire oscillatory and other alpha2-motor units started to fire
      oscillatory in synchronization with the first alpha2-motor unit. In a second case
      several alpha2-motor units fired oscillatory, but not in a synchronized manner.
      With the synchronization of the oscillatory firing alpha2-motor units again
      synchronizedly oscillatory firing of several alpha2-motor units appeared. When
      later on, several additional alpha1-motor units (FF-type) started to fire and in
      synchrony with the synchronizedly oscillatory firing alpha2-motor units (FR
      type), rhythmic muscle contraction and tremor were observed. Visible muscle
      contraction and tremor stopped, when the alpha1-motor units stopped firing, which
      could a.o. be achieved by the patient concentrating on the tremor. The single
      nerve-fibre action potential recording method showed that alpha1 and alpha2
      motoneurons in the cauda equine nerve roots fired oscillatory, that they could
      synchronize their firing and that these oscillatory firing motoneurons could
      build up an external loop to the periphery in the way that gamma-motoneurons and
      muscle spindle afferents were included in the rhythmic coordinated firing But the
      synchronization of oscillatory firing was only transient and the building up of
      an external loop to the periphery only occurred in non-Parkinson patients upon
      strong repetitive reflex stimulation. It is therefore concluded that in patients
      with Parkinson's disease there is firstly a lack of inhibition, so that
      motoneurons can start to fire oscillatory upon nearly no stimulation and there is
      secondly lack of mutual inhibition between oscillatory firing motoneurons, so
      that oscillatory firing motoneurons can synchronize their firing to give rise to
      rhythmic muscle contraction and tremor.

PMID- 16438346
TI  - Quantitative thermal sensory testing in patients with monomelic amyotrophy.
AB  - BACKGROUND: Quantitative thermal sensory testing (QST) is a non-invasive method
      to assess somatic small fibre dysfunction, which is not evaluated with routine
      nerve conduction studies (NCS). Monomelic amyotrophy (MMA), is a pure motor
      disorder with no sensory abnormalities on routine NCS, and has not been evaluated
      using QST. AIMS AND OBJECTIVE: Present study aimed to evaluate somatic small
      fibre involvement in MMA patients. Forty patients with MMA with no sensory
      abnormalities or routine NCS were evaluated using QST for thresholds of cold
      sensation (CS), warm sensation (WS), cold pain (CP) and warm pain (WP), using
      method of limits. These were compared with 40 age-matched controls. RESULTS: No
      abnormalities in thresholds for CS, WS, CP and WP were found in MMA group as
      compared to controls. CONCLUSION: QST thus failed to demonstrate any abnormality.
      Hence we conclude that MMA is a pure motor disorder, with no involvement of
      somatic small sensory fibres (A delta and C).

PMID- 16438348
TI  - Integrative re-organization mechanism for reducing tremor in Parkinson's disease
      patients.
AB  - A special movement therapy, called coordination dynamics therapy, has been
      reported to have the potential to improve central nervous system (CNS)
      functioning in Parkinson's disease patients. Electromyography using surface
      electrodes (sEMG) showed that the rhythmic muscle activity leading to
      Parkinsonian tremor was generated in the patients by the impairment of two kinds
      of inhibition. First, some premotor spinal oscillators organized themselves in
      the CNS neuronal networks without strong adequate input and second, the
      oscillators synchronized their firing to give rise to rhythmic muscle activity
      and tremor. In this paper it will be shown that highly coordinated arm and leg
      movements, generated when exercising on a special coordination dynamics therapy
      device, can reduce Parkinsonian tremor in amplitude and frequency and improve CNS
      functioning in the short-term memory. sEMG measurements showed upon exercising on
      the special coordination dynamics therapy device that the motor program improved
      in the short-term memory and tremor muscle activity became coordinated with the
      volitional motor program and reduced in size and frequency. Higher load
      exercising seemed to better reduce tremor muscle activity, probably because the
      physiologic CNS organization was more integrative then and could 'bind' stronger
      simultaneous pathologic tremor activity. Moreover, the rhythmic synchronized
      motor unit firing in different arm and leg muscles was synchronized or
      coordinated and changed in frequency and amplitude. It is concluded that the
      integrative re-organization mechanism to reduce Parkinsonian tremor is the phase
      and frequency coordination between neuron firing of the physiologic neuronal
      network state, generated by the highly coordinated arm and leg movements, and the
      simultaneous pathologic tremor network state, generated by the uninhibited
      neurons, firing synchronized oscillatory.

PMID- 16438349
TI  - A comparison of F waves in peripheral nerve disorders.
AB  - BACKGROUND AND AIM: F waves have become integral parts of nerve conduction
      studies in particular. F minimum (Fmin), the most commonly assessed latency,
      represents the largest and the fastest conducting fibers. The diagnostic yields
      of other F wave parameters are not obvious. In the present study, we aimed to
      determine the value of F wave parameters in commonly seen peripheral nerve
      disorders. MATERIAL AND METHOD: We studied the F responses in 118 patients who
      had been diagnosed with different types of neuropathies, clinically and
      electrodiagnostically, and 68 individuals were used as controls: A total of 470
      motor nerve conduction studies and related F-wave parameters were analyzed.
      DISCUSSION: F maximum (Fmax) was the most commonly seen abnormal parameter in the
      present study, although Fmin has until now been the most commonly studied
      parameter in clinics routinely. Abnormalities of F waves were more frequently
      seen in the patients compared to those in the control group and the differences
      were significant for carpal tunnel syndrome and upper extremity radiculopathies.
      CONCLUSION: This large database showed that F wave evaluations should include not
      only Fmin but also Fmax.

PMID- 16438350
TI  - Electromyographic validation of the pectoralis major and deltoideus anterior
      muscles in inverted "flying" exercises with loads.
AB  - Inverted 'flying" exercise with external loads of 25, 50, 75 and 100% of each
      individual maximum load in the pectoralis major and deltoideus anterior muscles
      was electromyographically analyzed in eleven male volunteers, using surface
      electrodes MEDI-TRACE-200 connected to a biological signals acquisition module
      coupled to a PC/AT computer. Electromyographic signals were processed and the
      effective values obtained were standardized through maximum voluntary isometric
      contraction. When the concentric phase of each muscle with the same load was
      statistically compared with the eccentric phase, it was observed that for all
      loads all the muscles presented significant electromyographic difference, and
      that the concentric phase was always higher. By analyzing the different loads for
      each muscle, it was noticed that in the concentric phase all the muscles
      presented significant electromyographic activity, being it higher with maximum
      load. When the effect of each load on different muscle in the concentric and
      eccentric phases was analyzed, the muscles presented a distinct activity profile.

PMID- 16438351
TI  - Cerebral palsy improvement achieved by coordination dynamics therapy.
AB  - Low-intensity coordination dynamics therapy, including crawling, treadmill
      walking, jumping on spring-board and exercising on a special coordination
      dynamics therapy device, was applied for 3 months (4 hours therapy per week) to 8
      cerebral palsy patients (average age 15 years, range 7-27). All patients
      improved. The organization of the CNS, quantified by the low-load coordination
      dynamics between arm and leg turning movements, when exercising on the special
      coordination dynamics therapy device, improved by 46 +/- 17% (range 33-60%) for
      forward and by 48 +/- 15% (range 22-66%) for backward moving. Also improved the
      exercised crawling, jumping and walking, although not as much as the CNS
      organization quantified by coordination dynamics. The motor programs of the
      tibialis anterior, gastrocnemius, biceps brachii, and triceps brachii muscles,
      measured by surface electromyography (sEMG), improved only little. Evidence is
      provided for sEMG being a very suitable tool for optimizing the movement
      performance and the therapy since sEMG records show under what exercise
      conditions the recorded motor programs are best. However coordination dynamics,
      i.e. the integrative parameter for quantifying CNS organization, is better to
      show the progress in CNS functioning than movement and EMG improvements. When the
      patients stopped therapy, the value of their coordination dynamics, worsened 24%
      after 6 months. In one patient the coordination dynamics therapy was continued
      intensively for further 3 month, including 20 hours exercise per week. The value
      of the coordination dynamics even improved altogether by 85% and 82% for forward
      and backward turning movements respectively, and simultaneously movements,
      vegetative (sleep) and higher mental functions (aggressivity, learning capacity)
      showed strong improvements. The improvements of coordination dynamics for low
      intensity therapy (46%, for forward movements) and additional high-intensity
      therapy (85%) lie within the recovery range for stroke (70%) and brain injury
      (69%) after 3 months of intensive coordination dynamics therapy. There is
      therefore indication that the CNS functioning in cerebral palsy patients can be
      improved by learning as much as the CNS functioning can be repaired by re
      learning in stroke and brain injury. The improvement of the CNS functioning
      suggests that cerebral palsy can partly be cured if intensive coordination
      dynamics therapy is administered for 1 to 2 years. It is further suggested that
      inabilities, including mental inability, are diseases which can partly be cured
      rather than inabilities.

PMID- 16438352
TI  - Beware of Profmed.

PMID- 16438353
TI  - Response to Dr Swart's letter (September issue 2005, Vol 60 no 8).

PMID- 16438354
TI  - The context of a dental school in a post-apartheid South Africa--some
      reflections.

PMID- 16438355
TI  - Faculty of Dentistry MEDUNSA 1980-2005.

PMID- 16438356
TI  - Global trends in dental fluorosis from 1980 to 2000: a systematic review.
AB  - AIM: To determine trends in fluorosis prevalence at water fluoride levels <0.3,
      >0.3 to <0.7, and >0.7 to 1.4 ppm from 1980 to 2000. METHODS: A systematic review
      of 55 published articles identified in a Medline search for peer-reviewed
      articles on fluorosis published from 1 January 1980 to 31 December 2000. The
      prevalence recorded with any fluorosis index was pooled and the trends over time
      were determined in the three water concentration categories. RESULTS: The
      fluorosis prevalence for the three fluoride categories were 16.7, 27.4 and 32.2
      percent, respectively. A 16-fold and a 2-fold increase in fluorosis prevalence
      compared with reported rates in the 1940s was seen in non-fluoridated (= 0.3 ppm
      F) and fluoridated (>0.7 to = 1.4 ppm F) areas, respectively. There has been an
      increase in fluorosis prevalence over time in the three fluoride water
      concentration categories but linear regression analysis showed that none are
      significantly different from zero. CONCLUSION: This systematic review concurs
      with recent reports of an increase in fluorosis prevalence in fluoridated and non
      fluoridated communities.

PMID- 16438357
TI  - Impaired tooth eruption: a review.
AB  - Eruption is the continuous process of movement of a tooth from its developmental
      location inside the jaw to its functional location in the mouth. Impaired tooth
      eruption, where this process is disturbed, is common in dental practice. It may
      manifest either as delayed or complete absence of eruption. Although unerupted
      teeth are usually asymptomatic, they may cause cosmetic and pathologic
      complications. The purpose of this article is to provide a review on the
      pathogenesis and differential radiographic interpretation of impaired tooth
      eruption.

PMID- 16438358
TI  - The role of ivory in the survival of the African elephant.
AB  - The unique chequered pattern of polished ivory has created a perverted commercial
      demand for elephant tusks. The morphologic basis of the pattern, which makes
      ivory a sought after product for the manufacturing of works of art, is discussed.
      Chemical analyses of ivory holds great potential in tracing the source of
      illegally harvested tusks and exposing poorly managed elephant sanctuaries. The
      impact of uncontrolled ivory hunting on the population genetics of the African
      elephant is briefly reviewed.

PMID- 16438359
TI  - Herpes zoster post-herpetic neuralgia.
AB  - Post-herpetic neuralgia (PHN) is the most frequent complication of herpes zoster
      and often results in significant morbidity and a reduction in the patient's
      quality of life. The peripheral nerve injury that occurs during the acute phase
      of herpes zoster (HZ) leads to an abnormal tonic impulse discharge from primary
      nociceptive afferent neurons which induce slow temporal summation. This "wind-up"
      phenomenon is responsible for continuous partial depolarisation of second-order
      neurons with increased spontaneous impulse discharge and expanded receptive
      fields within the dorsal horn nociceptive neurons. The abnormal central
      processing involves the activation of N-methyl-D-aspartate (NMDA) receptors
      resulting in neuropathic pain, characterized by spontaneous pain, hyperalgesia
      and allodynia which is typical of PHN. In addition, tonic input from non
      nociceptive AB afferent neurons, maintained by sympathetic efferent activity,
      contribute to the development and maintenance of neuropathic pain in general, and
      a burning sensation in particular.

PMID- 16438360
TI  - Expectations and perceptions of professional satisfaction in a cohort of Medunsa
      dental graduates in compulsory community service.
AB  - A study was initiated at Medunsa to track the expectations and perceptions of
      career satisfaction in a cohort of 2003 dental graduates. This paper reports on
      the expectations of career satisfaction held by this group shortly before
      graduating in 2003 from the Dental Faculty at Medunsa as well as perceptions
      gained from the year of Compulsory Community Service (CCS) during 2004. A
      previously validated questionnaire, the Dentist Satisfaction Survey (DSS) was
      self administered to the 2003 (N=43) group of learners. An expanded survey
      instrument the Dentist Satisfaction Questionnaire (DSQ) was self administered to
      the 2004 (N= 33) group of dentists. The 2004 survey included a Quality of Life
      (QoL) section as well as two visual analogue scales (VAS) that measured overall
      job satisfaction and dentistry-related stress. The respondents also had the
      opportunity to make any comments they felt could add value to their responses.
      Regression analyses were performed on both groups. The best set of predictor
      variables for overall job satisfaction in the 2003 group were Respect and Stress.
      Analysis of the data on the 2004 group revealed that Professional Time, Practice
      Management,

PMID- 16438361
TI  - An introductory report on a new cephalometric method: the Dawjee analysis.
AB  - A new method of lateral cephalometric analysis referred to as the Dawjee analysis
      is introduced. Landmarks, planes and angles are defined, and the technique is
      outlined. The Dawjee analysis is primarily focused on evaluating craniofacial
      structures in the vertical dimension and this introductory presentation
      demonstrates its application in both open and deep bite cases. Studies are in
      progress to develop a set of standardised values for this technique in a South
      African population sample.

PMID- 16438362
TI  - Advances in light curing units and curing techniques: a literature review.
AB  - There exists a constant need for a dental curing light that works reliably and
      conveniently in the general practitioner's office and can be used effectively for
      all the different curing procedures. Due to the need for improved physical
      properties of resin based composites (RBCs) and less stress at the marginal
      interface, light curing units (LCUs) experienced significant advances in the past
      years. The dental industry has focused on reducing the curing time by developing
      higher intensity curing lights and by altering the resin composition and photo
      initiator concentration. As a result the dentist can now choose from a vast
      variety of curing lights, light intensities and curing methods. This article
      presents a review of the advances in light curing units and curing techniques, as
      well as the scientific principles that guided past developments and that will
      influence future advances.

PMID- 16438363
TI  - Malocclusion among 12-year-old school children in Mankweng, Limpopo Province of
      South Africa.
AB  - Consent was obtained from all relevant authorities to undertake an
      epidemiological survey to determine the occlusal status of a sample of 12-year
      old Black school children in Mankweng Circuit, Limpopo Province. The examination
      was carried out using the Dental Aesthetic Index (DAI) criteria, under conditions
      prescribed by the WHO in 1987. The results were analysed using the Kotmogorov
      Smirnov Test. The results of the study showed that forty seven percent (47%) of
      the subjects required orthodontic treatment, in the categories: definitive 20%,
      severe 13% and handicapping 14%. There is a proven need for orthodontic treatment
      among 12-year-old Black school children in Mankweng. Since there is no government
      hospital or clinic to provide such treatment, a centre should be established.

PMID- 16438364
TI  - General practitioner's radiology case 37. Multiple calculi (sialolithiasis).

PMID- 16438365
TI  - [Microbiocenosis of parietal mucin in the gastrointestinal tract of rats].
AB  - The qualitative and quantitative composition of the microbial community in
      parietal mucin at different areas of the gastrointestinal tract (GIT) of rats was
      revealed. The pronounced variability in the quantitative and qualitative
      characteristics of microbiocenosis in parietal mucin of rats at different
      sections was revealed. The differences were most pronounced in the passage from
      upper to lower GIT sections, the large intestine found to be the richest
      biocenosis. The microbial composition of rat feces was faintly associated with
      the GIT parietal microbiocenosis. The individual areas of GIT mucosa were unique
      of their microbial characteristics and organization. This makes it possible to
      regard them as relatively independent biotopes and indicates that it is
      impossible to evaluate the microbial community by one of the colonic mucosal
      sifes.

PMID- 16438366
TI  - [Antilactoferrin activity of microorganisms].
AB  - The detection rate of the antilactoferrin sign and the level of its manifestation
      in 165 strains of different microbial species, isolated from patients with
      inflammatory diseases and intestinal dysbacteriosis, were analyzed. The detection
      rate of antilactoferrin activity was 43 - 90% for Escherichia coli strains, 20 -
      86% for Staphylococcus aureus, 60 - 100% for Klebsiella pneumoniae, 76 - 78% for
      Candida albicans, isolated from different biotopes of man. Most frequently and
      with high levels of manifestation this sign was registered in strains isolated
      from the reproductive tract of women. The detection rate of this sign and the
      level of its manifestation in bacteria of the vaginal and cervical
      microbiocenosis, isolated from patients, were higher in comparison with healthy
      persons. The inverse dependence between the level of the antilactoferrin activity
      of microflora and the content of lactoferrin during the inflammatory process in
      women was established.

PMID- 16438367
TI  - [Fatty-acid composition of cells and lipopolysaccharides in different Yersinia
      species under the conditions of growth at low temperature].
AB  - Y. pestis, Y. pseudotuberculosis, Y. enterocolitica, Y. frederiksenii, Y.
      intermedia, Y. kristensenii and Y. ruckeri grown at 4 degrees C were
      characterized by fatty acid composition with a high content of C16:1 and C18:1,
      as well as the proportion of saturated to nonsaturated fatty acids equal to, on
      the average, 2.0. In Yersinia lipopolysaccharides a relatively high level of
      C16:1 and C12:0 was observed with the prevalence of 3-OH-C14:0. In the fatty-acid
      spectra of both cells and lipopolysaccharides no essential difference was noted.
      Thus, during growth at low temperature differences, earlier detected in the
      studied Yersinia species grown at 37 degrees C and making it possible to divide 7
      Yersinia species into 2 groupes, were completely leveled. These results confirmed
      the close phylogenetic relationship between the Yersinia species under study and
      were indicative of more pronounced biological community of Yersinia under the
      conditions of growth at low temperature.

PMID- 16438368
TI  - [Morbidity in acute virus hepatitis B on the territory of Kabardin-Balkaria].
AB  - Morbidity in acute virus hepatitis B (AVHB) in Kabardin-Balkaria during the
      period of 1992 to 2003 was analyzed. The dynamics of changes in the age groups of
      AVHB patients, as well as in the structure of the transmission routes of the
      disease, was analyzed. The level of AVHB morbidity in the Kabardin-Balkar
      Republic was lower in recent years than the average level of such morbidity in
      the whole of Russia. The sharply defined irregularity in the territorial
      distribution of AVHB cases was established. The highest morbidity rates in AVHB
      were registered in Nalchik, as well as in Chegem and Prokhladnensk regions. The
      leading role in the formation of the morbidity in acute virus hepatitis B on the
      territory of Kabardin-Balkaria belongs to Nalchik, where 56.8% of AVHB cases were
      registered. In the structure of the transmission routes of AVHB the prevalence of
      artificial paths was noted; among them, the highest proportion belonged to
      parenteral medical manipulations in outpatient clinics (32.9%). The proportion of
      AVHB cases associated with the intravenous use of drugs was 6.9%. In the age
      structure of AVHB patients adults prevailed, and among them the highest number of
      cases was registered in the age groups of 20 - 29 years and 30 - 39 years. In
      2002 the total proportion of AVHB cases among the patients of these age groups
      reached 68.3%.

PMID- 16438369
TI  - [Genotypes of rubella viruses circulating in Russia].
AB  - The phylogenetic analysis of rubella virus gene E1 in 6 strains isolated in
      Russia in 1967 - 1997 and in 36 isolates obtained from different countries during
      the period of 1963 - 1997 was carried out. Most of the genotypes were classified
      with genotype 1--these were strains from Europe, North America, Japan, China.
      Strains not included into genotype 1 were found to exhibit accelerated evolution
      in comparison with strains of genotype 1, but this was only seeming acceleration,
      as the strains of genotype "non-1" formed 3 sharply defined groups, standing
      quite apart, whose intragroup divergence was less or equal to that within
      genotype 1. The genetic distance between these 3 groups and genotype 1 was
      essentially higher than the intragroup divergence and equal to 6.20 - 8.21%. The
      data obtained in this study made it possible to regard these groups as separate
      genotypes. The suggestion was made that five strains isolated in Russia should be
      classified with genotypes IIB or III in contrast to strains of genotype II from
      India, China, South Korea, Italy.

PMID- 16438370
TI  - [Characteristics of the immune status in specific and nonspecific prophylaxis of
      influenza in elderly persons].
AB  - The results of the comparative analysis of the immunological effectiveness of the
      anti-influenza vaccine Vaxigrip, the inferferon inductor Arbidol and their
      combination in 125 elderly persons are presented. In the process of
      investigations the immunomodulating activity of the preparations under study was
      noted; this activity was manifested by the increase of the absolute and relative
      number of cells, carrying markers CD3+, CD4+ and CD16+, but not CD8+, CD19+ and
      CD25+, the normalization of the immunoregulatory index and the stimulation of the
      phagocytic function in the absence of essential influence on the level of HLA-DR+
      expression and the concentration of immunoglobulins of the main classes. An
      increase in the frequency of seroconversions and the multiplicity of growth in
      the titers of specific antibodies to influenza viruses A (H1N1 and H3N2) and B,
      most pronounced in persons immunized with the vaccine simulianeouslywith the
      injection of Arbidol, was established.

PMID- 16438371
TI  - [Clinical studies of vaccine TEOVac under the conditions of remote
      revaccination].
AB  - In the clinical trials of vaccine TEOVac in lower and reglamented doses under the
      conditions of remote vaccination, carried out on 11 volunteers, local reactions
      in the form of hyperemia, gingival edema (1 vaccinee), faucial hyperemia,
      enlargement of submaxillary lymph nodes (2 vaccinees) were registered in some of
      the vaccines; in one vaccinee systemic postvaccinal reaction of medium gravity
      was observed. Revaccination produced no negative effect on the hematological and
      biochemical characteristics of the blood, as well as on the urine
      characteristics. The study of the sensitizing vaccine to the antigens of the
      accumulation substrate (chick embryo), as well as its influence on the
      development of autoimmune reactions, revealed the absence of the allergic action
      of the preparation and its influence on autoimmune processes in the vaccines. The
      trial of the smallpox vaccine in tablets under the conditions of the primary
      immunization of adults was the topical and most promising trend in the
      improvement of smallpox vaccination, as the preparation TEOVac proved to be safe,
      in contrast to the traditional smallpox vaccine introduced by the scarification
      method, for both vaccines and nonimmunized persons having contacts with them.

PMID- 16438372
TI  - [Evaluation of the antimicrobial potential of immune sera].
AB  - The inhibiting activity of blood sera obtained from 20 volunteers immunized with
      the multi-component vaccine "PYOPOL", 25 nonimmune donors and 7 lots of human
      antistaphylococcal immunoglobulin with respect to Staphylococcus aureus,
      Escherichia coli, Proteus vulgaris and Pseudomonas aeruginosa has been studied in
      the liquid nutrient medium with the use an automated microbiological analyzer.
      The sera of donors immunized with the vaccine "PYOPOL" have been found to possess
      high antimicrobial activity, comparable with the definite concentration of the
      antiseptic agent "Myramistin". The proposed method may be recommended for the
      evaluation of the bacteriostatic activity of different immuno- biological
      preparations.

PMID- 16438373
TI  - [Influence of dendrite cells, generated with the use of immunomodulators of
      microbial origin, on the proliferative and cytotoxic activity of lymphocytes].
AB  - The influence of ripe dendrite cells (DC) on the proliferative activity of
      mononuclear leukocytes and the cytotoxic activity of lymphocytes of syngenic mice
      was studied. As inducers of DC ripening, the combination of antigenic components
      incorporated into the vaccine "lmmunovac Bh-4", (Klebsiella pneumoniae, Proteus
      vulgaris, Escherichia coli, Staphylococcus aureus), as well as K. pneumoniae LPS
      and TNF-alpha, were used. This study demonstrated that DC activated with these
      preparations enhanced the proliferative activity of mononuclear leukocytes, the
      activity of Bh-4 being higher than that of K. pneumoniae LPS. The increase of
      proliferative activity was accompanied by a rise in the cytotovicity of mouse
      lymphocytes with respect to the NK-sensitive tumor line YAC-1 or Ehrlich tumor
      cells. The incubation of the lymphocytes with ripe DC (with the use of the
      preparations under study as ripening inducers), loaded with tumor antigens, made
      it possible to obtain cytotoxic lymphocytes having high cytotoxic activity with
      respect, mainly, to those tumor lines from which lysates for the treatment of DC
      had been produced. The activation of DC with bacterial immunomodulators led to an
      increase in the antigen-presenting function of these cells, to their higher
      capacity for regulating the differentiation of mononuclear leukocytes and for
      activating the cytotoxicity of natural killers.

PMID- 16438375
TI  - [Virulent properties of hospital strains of bacteria of the Burkholderia cepacia
      complex, isolated in hospitals of Moscow].
AB  - The results of the study of hospital strains of the B. cepacia complex, isolated
      in hospitals of Moscow, with the use of phenotypical and molecular-genetic
      methods are presented. The phenotypical methods made it possible to differentiate
      Russian strains and classify them with a group of genomovars (I, III, IV). As the
      result the epidemic importance of the strains with epidemic markers, having
      specific characteristics for every clinic, was determined. The detection of the
      collection of genes cepI and cepR in the strains made confirmed the epidemic
      importance of the stains which had, due to the regulatory "quorum sensing" (QS)
      system, the potential capacity for inducing infection and persisting in the
      patient's body. The presence of gene cepR in all strains and the absence of gene
      cepl in 33% of strains gave evidence to suggest that in some strains the
      activation of the production of pathogenicity factors required the presence of
      other bacteria having the fully developed QS system. Thus, the new complex
      approach with the use of phenotypical and molecular-genetic methods permits more
      precise identification of the source of hospital infection induced by the
      bacteria of the B. cepacia complex.

PMID- 16438374
TI  - [Biological properties of salmonellae and local immunity in Salmonella
      infection].
AB  - The comparative study of the biological properties of S. enteritidis and S.
      typhimuruim, isolated from patients and convalescent carriers, was carried out.
      Factors inactivating the components of the local immunity of the intestine
      (lysozyme, complement, lactoferrin, IgG, IgM and IgA) were detected in the
      causative agents of Salmonella infections. The spread and expression degree of
      properties of a causative agent were serovar-depended: high penetration
      characteristics and the expression of anti-lactoferrin and anti-immunoglobulin
      activity were characteristic of S. typhimurium. S. enteritidis strains isolated
      from patients with carrier state formed in the convalescence period were found to
      have higher persistence level. In co-profiltrates obtained from carriers at the
      peak of the disease and during convalescence lower levels of IgM, IgG, sIgA,
      complement and lactoferrin were determined in comparison with those in
      coprofiltrates obtained from patients in whom no subsequent carrier state was
      formed. These results indicate that an increase in the persistence of
      salmonellae, occurring simultaneously with the local immunodeficiency,
      contributes to the prolonged survival of bacteria in the intestine.

PMID- 16438376
TI  - [The correction action of Phosprenyl and Gamavit on the functional activity of
      mouse peritoneal macrophages in response to high doses of Staphylococcus aureus
      alpha-toxin].
AB  - The study of the functional activity of peritoneal macrophages of BALB/c mice at
      different stages of the toxic action caused by S. aureus alpha-toxin (ST) was
      carried out. The analysis of the dynamics of toxic reaction revealed the main
      critical points of triggering necrotic processes: the first hour and day 2. One
      hour after the injection of large doses of ST a sharp increase in the process of
      antigen binding with its subsequent sharp decrease. Simultaneously, a decrease in
      the activity of the lysosomal enzymes cathepsin D and acidic phosphatase was
      established, which was indicative of the destabilization of both lysosomal and
      cellular macrophage membranes. The increase of oxygen metabolism on day 2,
      together with the release of lysosomal proteases into the extracellular area,
      correlated with the maximum death rate of mice and served as the main index of
      the development of necrosis. The prophylactic and therapeutic use of the
      preparations Gamavit and Phosprenyl revealed their antitoxic activity and
      capacityfor stimulating the level of natural body resistance.

PMID- 16438377
TI  - [Survival of Coxiella burnetii in soil].
AB  - For the first time the survival of Coxiella burnetii of five types in soils has
      been studied. The survival of C. burnetii has been found to depend on the content
      of organic substances in black earth, as well as soil temperature. The method for
      the prevention of an epidemic outbreak of Q fever directly under the natural
      conditions has been proposed.

PMID- 16438378
TI  - [Clinical and laboratory characterization of Ixodes tick-borne borreliosis in the
      Baikal area].
AB  - Materials on Ixodes tick-borne borreliosis (ITB) for the period of 2000 - 2003
      (i.e. 1,222 blood serum samples from patients with acute ITB and 629 patients
      with chronic ITB) were analyzed. The proportion of seropositive samples among
      those obtained from patients with acute and chronic ITB was determined with the
      use of the indirect immunofluorescence test. In addition, data on different
      clinical forms of the disease were presented. A high percentage of neurological
      manifestations in the early period of ITB (31%) and in the late period of the
      disease (72.8%) was noted. The conclusion was made concerning the necessity of
      using several diagnostic methods for more exact determination of the structure of
      the disease.

PMID- 16438379
TI  - [Natural foci of leptospirosis in Moscow in 1995 - 2004].
AB  - The article deals with the results of the 10-year study of the synanthropic urban
      foci of leptospirosis on the territory of Moscow. Information on the
      manifestation of the activity of the foci under study, rodents serving as the
      reservoir of infection in these foci, the etiological structure of the
      leptospires among these rodents, the state of leptospirosis morbidity among
      humans is presented.

PMID- 16438380
TI  - [Identification of the optochin-resistant Streptococcus pneumoniae strains].
AB  - So far the prevalent method of the identification of pneumococci in the routine
      diagnostic practice has included three tests: sensitivity to optoxin, solubility
      in biliary salts and reaction with omniserum. At present optoxin-resistant
      pneumococcal strains, as well as those giving dual reaction to solubility in
      biliary salts, occur sufficiently often thatconsiderably complicates the
      identification of this infective agent. We have summarized experience in the
      isolation of S. pneumoniae strains, resistant to optoxin and not soluble in
      biliary salts; in addition, the prospects of introducing the complex approach to
      the identification of a given culture with the use of molecular diagnostic
      methods into daily practice are evaluated.

PMID- 16438381
TI  - [The diagnostic specificity of the antigen-binding lymphocyte test in Neisseria
      induced infections].
AB  - Neisseria-induce different infections, but many representatives of this genus are
      saprophytes. In this connection it is important to evaluate the species, and for
      N. meningitidis also group specificity of the immunological diagnostics of
      meningococcal infection and gonorrhea. In this work the specificity of the
      antigen-binding lymphocyte test was studied in experiments with the immunization
      of rabbits and the examination of patients. In the tests of indirect rosette
      formation and its inhibition the role of antigenic relationships between
      different pathogenic and nonpathogenic Neisseria was excluded and the species and
      group specificity of our Neisseria immunoreagents, used in the diagnostics of
      meningococcal infection and gonorrhea, was proved.

PMID- 16438382
TI  - [Phenotypical differences of Helicobacter pylori strains isolated in Georgia].
AB  - The phenotypical differences of H. pylori strains isolated in Georgia have been
      evaluated. Among H. pylori isolates, these strains have been found to differ from
      typical ones in the morphology of their colonies, growth under microaerophilic
      and anaerobic conditions, alpha-hemolysin production, resistance to cephalotin
      and nalidixic acid. At the same time all the strains under study are no different
      from typical H. pylori strains in respect of their cell morphology, tinctoral
      properties, growth at different temperatures and their main biochemical
      properties.

PMID- 16438383
TI  - [Specific features of Helicobacter pylori infection and the character of immune
      response in patients with a severe course of duodenal ulcer].
AB  - The presence of genetic markers of vacA-positive strains with s1/s2 subtype (76%)
      with a high proportions (84%) of mixed genotype and detection in a breath air the
      ammonia at significantly high concentrations, have been found to be the specific
      features of H. pylori infection in patients with a severe course of duodenal
      ulcer. A low level of specific IgG antibodies, the growth of immunological
      inflammation markers and the depression of humoral immunity have been
      established.

PMID- 16438384
TI  - [Cytokine-stimulating activity of lipopolysaccharide of gram-negative bacteria
      and its role in antitumor immunity].
AB  - The review deals with the discussion of different mechanisms of the antitumor
      action of lipopolysaccharides (LPS), including the induction of endogenous cell
      mediators, the development of inflammatory and immune response and systemic
      metabolic changes. The complex action of these factors on the levels of cells,
      tissues, organs and the whole body led, in some cases, to the suppression or
      hemorrhagic necrosis of the tumor. These cases were regarded as analogous to the
      development of the septic syndrome when a cascade of reactions leading to the
      resorption of tumors was initiated and to chronic inflammation resulting, on the
      contrary, in the formation of pretumor status. The data on the role of cytokines
      in carcinogenesis are presented and the possible causes of established
      contradictions are discussed. The prospects of using LPS in the therapy of
      oncological diseases are discussed.

PMID- 16438385
TI  - [Ecological regularities of the existence of pathogenic Yersinia in soil
      ecosystems].
AB  - In this review the data on the ecology of pathogenic Yersinia in soil ecosystems,
      based on prolonged observations, were analyzed and summarized. In contrast to
      saprophytic species, ubiquitously spread in nature, pathogenic representatives of
      the genus Yersinia occurred only in the soil of natural foci and of these, Y.
      pestis were found only in the soil of burrows of the main carriers. The complex
      of abiotic and biotic factors (temperature, humidity, chemical composition,
      interactions in biocenosis) which determined the possibility of the existence of
      Yersinia in the soil environment and the preservation of their pathogenic
      properties was considered. Special attention was paid to their geno-phenotypic
      variability as the main factor of the adaptation of the causative agents of
      plague, pseudotuberculosis and intestinal yersiniosis in the environment.

PMID- 16438386
TI  - [Phenotypical and molecular-genetic typing of salmonellae: reality and
      prospects].
AB  - The importance of the intraspecific typing of salmonellae for effective
      epidemiological analysis is shown. The methods (phenotypical and genotypical),
      used for the epidemiological marking of salmonellae, are characterized, their
      advantages and drawbacks, as well as prospects of their further use, are given.
      The importance of the standardization of molecular-genetic methods to ensure data
      exchange between different laboratories and the investigation of international
      outbreaks of enteric infections is pointed out. The international projects
      PulseNet and Salmgene of the surveillance of Salmonella infection, based on
      genotyping of Salmonella isolates, are presented.

PMID- 16438387
TI  - [Interferon therapy of infectious diseases: the state of the problem and
      prospects].
AB  - The data contained in literature and obtained in our own investigations, aimed at
      the evaluation of the significance of interferon preparations for the correction
      of immunological disturbances are presented. A special place is given to the role
      of mild medicinal forms of interferon, the necessity of their use is grounded and
      good prospects for their inclusion into the complex therapy of infectious
      diseases are shown.

PMID- 16438388
TI  - [Cell apoptosis in the culture: specific features of manifestation and influence
      on the effectiveness of biotechnological production].
AB  - The development of large-scale biotechnological production with the use
      continuous cell-line cultures as producers revealed the role of apoptosis in the
      culture as a factor producing essential influence on the effectiveness of the
      process, the level of the accumulation of the target product and its quality. The
      limiting influence of apoptosis as the programmed death of cells in the culture
      was determined by a number of factors: the chemical composition, pH and chemical
      properties of the medium; the levels of glucose, amino-acid and vitamin
      depletion; the uniformity of oxygenation; temperature conditions; the mode of
      agitation and the intensity of hydrodynamic forces; the content of mitogenetic
      factors and toxins in the medium; the presence and activity of the expression of
      apoptosis stimulators and inhibitors. The presence of correlation between the
      intensity of apoptosis, cultural properties and the characteristics of the
      mitotic cycle of the cell line was shown. The latter made it possible to regard
      the biological properties of the producer culture as one of the leading factors
      modifying the process of the programmed death of cells.

PMID- 16438389
TI  - [Detection of Mycobacterium leprae with the use of the polymerase chain
      reaction].
AB  - The review deals with the problem of the detection of the causative agent of
      lepra in different biological samples with the use of polymerase chain reaction.
      Special attention is drawn to the characterization of the specificity and
      sensitivity of different target areas of M. leprae DNA.

PMID- 16438390
TI  - Single-dose ketamine administration induces apoptosis in neonatal mouse brain.
AB  - The activity of N-methyl-D-aspartate (NMDA) receptors is critical for neuronal
      survival in the immature brain. Studies have reported that chronic blockage of
      these receptors mediates apoptosis in neonatal animals. We investigated the
      apoptotic effect of a clinically relevant single dose of ketamine, an NMDA
      receptor antagonist, in the brain of neonatal mice. Seven-day-old ICR mice were
      injected with ketamine (1.25, 2.5, 5, 10, 20, and 40 mg/kg body weight,
      subcutaneously in 0.9% NaCl) or with 0.9% NaCl alone as control. Righting reflex
      testing was performed and mouse brains were examined at 24, 48, and 72 h and 7
      days after injection. The number of degenerating neurons was measured using
      silver staining. Apoptosis was confirmed by DNA fragmentation (terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling). We observed in the
      sensorimotor cortex and cerebellum of ketamine-treated mice extensive apoptosis,
      which was clearly dose-dependent and present even after a low dose of ketamine (5
      mg/kg). The most prominent apoptotic damage was detected 72 h post-injection (P <
      0.001 vs control), at doses ranging from 10 to 40 mg/kg. After 7 d the number of
      neurodegenerative neurons, at doses ranging from 5 to 40 mg/kg, remained
      significantly high. The brain weight was comparable to that of untreated control
      mice and no gross neurobehavioral effects in the righting reflex test or
      alteration in the pattern of behavior was observed. The results indicate that the
      administration of ketamine in a clinically relevant single dose triggers long
      lasting neuronal apoptosis in certain brain areas of neonatal mice. IMPLICATIONS:
      The administration of ketamine in a clinically relevant single dose to 7-d-old
      mice induced apoptosis in the sensorimotor cortex and cerebellum. This effect was
      dose-dependent and long lasting.

PMID- 16438391
TI  - Short-term dietary restriction modulates liver lipid peroxidation in carbon
      tetrachloride-intoxicated rats.
AB  - We investigated whether dietary restriction (DR) can protect the liver against
      the acute toxicity of carbon tetrachloride (CCl4). Adult female Wistar rats
      received a quantum of diet representing 75 and 50 percent of the food intake of
      control rats fed ad libitum (25% and 50% daily regimen, respectively) for 30
      days. A single dose of CCl4 (3 mL kg(-1) b.w.) was administered subcutaneously at
      the end of the feeding period. Lipid peroxidation, as thiobarbituric acid
      reactive substance, conjugated dienes, lipid hydroperoxides and the hepatic
      markers alanine transaminase, aspartic transaminase, and alkaline phosphatase
      were significantly decreased in food-restricted rats. The enzymic antioxidants
      superoxide dismutase, catalase, glutathione peroxidase and the non-enzymic
      antioxidant glutathione were significantly increased in both groups. The
      magnitude of liver damage after CCl4 treatment was lower in food-restricted
      animals than in ad libitum-fed animals. The results suggest that dietary
      restriction increases the resistance of the liver and protects against oxidative
      insult produced by an acute dose of CCl4.

PMID- 16438392
TI  - Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key
      enzymes in streptozotocin induced diabetic rats.
AB  - The enzymes of glucose and lipid metabolism are markedly altered in experimental
      diabetes. In the present study, we investigated the effect of tetrahydrocurcumin
      (THC), one of the active metabolites in curcumin, on the key hepatic metabolic
      enzymes involved in carbohydrate metabolism in streptozotocin-induced diabetic
      rats. Different doses of THC (20, 40, and 80 mg?kg body weight) were orally
      administered to diabetic rats for 45 days. The activities of hexokinase, glucose
      6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, fructose-1,6
      bisphosphatase, and sorbitol dehydrogenase in liver, and glycogen content in
      liver and muscle were assayed. In untreated diabetic control rats, the activities
      of the gluconeogenic enzymes were significantly increased, whereas hexokinase and
      G6PD activity and glycogen levels were significantly decreased. Both THC and
      curcumin were able to restore the altered enzyme activities to near normal
      levels. Tetrahydrocurcumin was more effective than curcumin. Our results indicate
      that the administration of THC to diabetic animals normalizes blood glucose and
      causes a marked improvement of altered carbohydrate metabolic enzymes.

PMID- 16438393
TI  - Hyperbaric oxygenation and antioxidant vitamin combination reduces ischemia
      reperfusion injury in a rat epigastric island skin-flap model.
AB  - Reperfusion injury, caused by free oxygen radicals, is a chain of events that
      occurs in tissues exposed to a constant period of ischemia. The antioxidant
      vitamins E and C (VEC) and hyperbaric oxygenation (HBO) have beneficial effects
      in treating ischemic tissues following skin flap operations. In our study, we
      aimed to compare the effects of VEC and/or HBO in ischemia-reperfusion injury
      induced by free oxygen radicals in an experimental rat epigastric island skin
      flap model. Eight hours of ischemia was provided by clamping the inferior
      epigastric pedicle following the flap elevation. The flap survey was determined
      to be 28.6% in controls, 59.2% in HBO group, 66.3% in VEC + HBO group, and 82% in
      VEC group (p < 0.05). We conclude that although HBO and/or VEC increased the flap
      viability significantly by reducing ischemia-reperfusion injury, the most
      promising results were obtained in the antioxidant vitamins group.

PMID- 16438394
TI  - Efficacy of HCG and ovarian steroids in the maintenance/interruption of pregnancy
      in-albino rats.
AB  - We investigated the efficacy of human chorionic gonadotrophin (HCG) and ovarian
      steroids in the maintenance/interruption of pregnancy in normal pregnant rats.
      Holtzman's strain rats were laparotomized to observe the number of implantations.
      In this study, continuous administration of HCG (5 IU) to normal pregnant rats,
      from day 8 through days 14 or 19, interrupted gestation, resulting in fetal
      resorption with many placentomas and placental scars. By contrast, a single
      injection of HCG (5 IU or 1 IU) on day 8 had no deleterious effect on pregnancy,
      except that the percent fetal survival was slightly reduced, attributable to a
      slight hyperstimulation of the ovaries of the pregnant rats. One possibility is
      that prolonged treatment with HCG might have caused progesterone/luteal hormone
      deficiency with a concomitant increase in estrogen secretion, resulting in the
      interruption of pregnancy. Hence, here we tested whether progesterone (5 mg) or
      estradiol-17beta (1 microg) administered to HCG treated rats could compensate
      this deficiency and maintain pregnancy. The results indicate that these steroids
      cannot prevent the interruption of pregnancy induced by the continuous
      administration of HCG, possibly due to an overstimulation of the ovaries by
      gonadotrophin.

PMID- 16438395
TI  - Responsiveness of vascular alpha1-adrenoceptors of diabetic rat knee joint to
      phenylephrine in acute inflammation.
AB  - In diabetic angiopathy, responsiveness of alphal-adrenoceptors in blood vessels
      increases. The aim of this study was to investigate the vasoconstrictor response
      of knee joint blood vessels to phenylephrine (a 1-adrenoceptor agonist) in
      diabetes and acute inflammation. Acute knee joint inflammation was induced by the
      intraarticular injection of a 3% kaolin/3% carrageenan suspension. Diabetes was
      induced by the intravenous injection of alloxan (70 mg/kg). Male albino rats
      weighing 70 to 90 g each were divided into the following 4 groups: untreated
      controls, diabetic, inflammatory, and diabetic inflammatory. The blood flow of
      the knee joint was measured using the laser Doppler flowmetry (LDF) technique.
      Vasoconstriction of the articular microvascular was measured in response to the
      topical application of different concentrations (10(-7) to 10(-3) mol)
      phenylephrine. The results of this study show that (a) increased knee joint
      diameter and circumference due to inflammation and the knee joint basal blood
      flow were significantly lower in diabetic than in control rats; (b) the
      responsiveness of alphal-adrenoceptors decreased in kaolin/carrageenan-induced
      acute inflammation; (c) carrageenan-induced acute inflammation did not decrease
      the responsiveness of alphal-adrenoceptors in diabetic rats. We conclude that
      diabetes inhibits the reductive effect of acute inflammation on the
      responsiveness of alpha1-adrenoceptors in rats.

PMID- 16438396
TI  - The tort reform bandwagon.

PMID- 16438397
TI  - Reducing the number of uninsured.

PMID- 16438401
TI  - Surgery for hepatic cancer: are we making progress?

PMID- 16438402
TI  - Death of the curbside consult?

PMID- 16438403
TI  - Internet safety.

PMID- 16438410
TI  - [Aging: loss of senses, loss of sense?].

PMID- 16438409
TI  - [Aging of the senses].

PMID- 16438411
TI  - [Grooming the elderly person, a nursing care charged with caring for the senses].

PMID- 16438412
TI  - [From listening in the hospital to its acoustic management].

PMID- 16438413
TI  - [Alteration of the five senses and home care].

PMID- 16438414
TI  - [The senses of life].

PMID- 16438415
TI  - [A senses' workshop for maintaining communication].

PMID- 16438417
TI  - [Educating nursing aide students to the care of the elderly with vision
      disorders].

PMID- 16438416
TI  - [Creation of a massage workshop by and for the patients].

PMID- 16438418
TI  - [From noise... to their music].

PMID- 16438419
TI  - [Talking about one's time: life histories and writing workshops].

PMID- 16438420
TI  - [Utility of a daily foot examination in geriatric medicine].

PMID- 16438421
TI  - [Nursing and medical psychological aides, how do they complement each other?].

PMID- 16438422
TI  - iPLEDGE allegiance.

PMID- 16438423
TI  - What is your diagnosis? Progressive systemic sclerosis (scleroderma).

PMID- 16438424
TI  - Psoriasis guttata with palmoplantar involvement clinically mimicking secondary
      syphilis.
AB  - Papulosquamous eruptions involving the palms and soles are thought to be
      particularly suggestive of secondary syphilis. Alternative diagnoses exist,
      however, and include psoriasis guttata, atypical pityriasis rosea, and pityriasis
      lichenoides chronica (PLC). We describe the case of a patient with an abrupt
      onset of psoriasis guttata and extensive palmoplantar involvement. Results of
      serologic testing were negative for treponemicidal antibodies. Results of
      histopathologic examination demonstrated psoriasiform dermatitis with neutrophils
      in the epidermis; plasma cells were absent. Spirochetes were not demonstrated in
      a tissue sample using silver or immunohistochemical stains for Treponema
      pallidum. A broad differential diagnosis is required when evaluating
      papulosquamous eruptions with palmoplantar involvement. Although not well
      referenced in the medical literature, psoriasis guttata can indeed cause
      palmoplantar lesions that mimic those of secondary syphilis.

PMID- 16438425
TI  - Alopecia in association with sexually transmitted disease: a review.
AB  - In a patient with a sexually transmitted disease (STD), alopecia may be an
      important associated finding and can provide clues to diagnosis. This review
      focuses on the relationship between hair loss and STDs. Specifically, we review
      alopecia in association with syphilis and human immunodeficiency virus (HIV)
      infection and the medications used to treat these infections. In addition, we
      review the literature regarding the putative association between alopecia areata
      and cytomegalovirus (CMV).

PMID- 16438427
TI  - Subcutaneous granuloma annulare of the scalp: a case report and case review.
AB  - Subcutaneous granuloma annulare (SGA) is a benign inflammatory disorder that may
      be alarming in its presentation because of its rapid growth and extensive
      differential diagnosis. The purpose of our study was to improve the appropriate
      evaluation and management of pediatric patients with subcutaneous scalp nodules.
      This article presents the clinical presentation, histopathologic data,
      evaluation, and management of a patient with subcutaneous scalp nodules diagnosed
      as SGA. Additionally, the clinical data of all other cases of SGA diagnosed at
      our institution over a 9-year period were reviewed. The majority (72%) of SGA
      patients encountered at our facility were children. Most of the SGA lesions were
      located on the extremities; however, all of the lesions located on the scalp were
      in children. This article reviews the differential diagnosis and workup of scalp
      nodules. In evaluating the patient with subcutaneous scalp nodules, we conclude
      that SGA should be added to the differential diagnosis.

PMID- 16438426
TI  - Basic fibroblast growth factor treatment for skin ulcerations in scleroderma.
AB  - We report the use of topical application of recombinant human basic fibroblast
      growth factor (rhbFGF) to successfully treat therapy-resistant, chronic leg
      ulcers in scleroderma. Endothelial cell FGF receptors are directly stimulated by
      bFGF; also, bFGF promotes the regeneration of capillary-rich granulation tissue.
      We conclude that topical bFGF may be a powerful new pharmacologic tool for
      treating severe skin ulcers.

PMID- 16438428
TI  - All together now. Building connects diverse activities of Mayo Clinic complex.

PMID- 16438429
TI  - Lessons learned. Recent disasters give reason to rethink emergency management
      strategies.

PMID- 16438430
TI  - Site selection in six steps. Where to build for now and the future.

PMID- 16438431
TI  - Sneak preview: What changes are coming up in the revised design guidelines?

PMID- 16438432
TI  - Eight steps to quality: how one hospital maintains a high level of ES
      performance.

PMID- 16438433
TI  - Where are we heading?

PMID- 16438434
TI  - Weight loss surgery: are the results worth the risks?

PMID- 16438435
TI  - Adding a little more 'PEPP' to the renal community.

PMID- 16438436
TI  - Thriving nephrology practice embraces technology, CKD care, research.

PMID- 16438437
TI  - Disaster preparedness and recovery in the dialysis facility.

PMID- 16438438
TI  - Sorbent dialysis in the third millennium.
AB  - Thus, in a variety of ways, the unusual relationship between patient and machine
      in sorbent dialysis reduces the risks that are inherent with single pass systems.
      This pays dividends for both patients and professionals. Given the growing need
      for home and self-care dialysis in the new millennium, the time is right for the
      introduction of an updated, revitalized sorbent dialysis system.

PMID- 16438439
TI  - Coaching patients to succeed in adhering to a renal diet.
AB  - As nephrology dietitians, we have the responsibility to provide useful
      information in understandable terms. This may involve different methods of
      education depending on the patients learning preferences. Once this is
      accomplished and we have checked for patient understanding, it is then the
      responsibility of the patient to adhere to the recommendations. Not all patients
      will follow our advice, even if they understand the rationale and know what they
      need to do. That is their choice. However, it is our responsibility to ensure we
      have provided patients with the tools they need in a way that is most conducive
      to modifying their behavior.

PMID- 16438440
TI  - Managing homeless dialysis patients.
AB  - Although our dialysis facility is located in a rural area, we noticed an
      increasing number of homeless patients requiring treatment. After researching the
      issue of homelessness in dialysis patients, we found little has been reported on
      the subject. We examined the characteristics of our homeless dialysis patients as
      well as the effects these patients have on the multidisciplinary dialysis care
      team. Six homeless patients were dialyzing in our in-center hemodialysis unit
      (monthly census averages 105-110 patients) in April 2005. All of the homeless
      patients were men; five of the six were African American, five had a history of
      substance abuse, and four a history of alcohol abuse. The mean age of these
      patients was 45.75 years, and the mean number of months on dialysis was 46.4. All
      were single (5 divorced, 1 never married), and 5 had a history of psychiatric
      illness. All six had Medicare coverage. The patients found shelter through local
      community shelters, the Salvation Army, and in their automobiles. The medical,
      nursing, dietary, and social aspects of the care provided by the dialysis
      multidisciplinary team members are discussed as it pertains to the care of
      homeless dialysis patients.

PMID- 16438441
TI  - The risks of nanotechnology.
AB  - Nanotechnology is extremely fashionable, especially in the medical products
      sector, but questions are now being asked about the potential for new health
      risks that are introduced with the products and processes associated with
      nanotechnology. This article discusses some of the principal findings of a new
      report on this subject.

PMID- 16438442
TI  - The revolution in advanced wound-care converting.
AB  - In the advanced wound-care sector, there is an accelerating trend away from
      serial batch production towards transformational, continuous and integrated
      process lines. This is creating new standards and challenges in converting
      processes, which run faster, produce less waste and require fewer operators to
      run them. This article identifies those challenges and highlights the increasing
      importance of the relationship between wound-care manufacturer, materials science
      and the design of the converting process.

PMID- 16438443
TI  - Materials characterisation of Biomedical tents.
AB  - This article reviews the use of materials characterisation to optimise the
      bioengineering and manufacturing of stents and thereby provide assurance of
      performance in clinical applications. The capabilities of today's sophisticated
      techniques are described.

PMID- 16438444
TI  - Regenerative medicine: revolution in the making.

PMID- 16438445
TI  - Analysis software can put surgical precision into medical device design.
AB  - Use of finite element analysis software can give design engineers greater freedom
      to experiment with new designs and materials and allow companies to get products
      through clinical trials and onto the market faster. This article suggests how.

PMID- 16438446
TI  - European requirements for product returns.
AB  - Considerable uncertainty exists regarding European requirements for withdrawing a
      product from the market because of product performance problems that are not
      related to serious health risks or death. This article discusses the requirements
      for product returns or other related actions that are outside the scope of the
      recall notification requirements defined in the medical device Directives.

PMID- 16438447
TI  - The industry in Europe: more together than apart.
AB  - How different is the United Kingdom from the rest of Europe? This, the second of
      a three-part report on the findings of Medical Device Technology's annual market
      survey, looks at a country whose health-care delivery is going through
      considerable change.

PMID- 16438448
TI  - Create products by going virtual.
AB  - A virtual organisation is a business that outsources the majority of its
      operations. This enables it to be highly responsive to the market and to fast
      track the creation of specialist products. Tips for the successful implementation
      of this approach are offered here, with an example of one profitable business.

PMID- 16438449
TI  - Instructions for use and the new EU languages.
AB  - Since the expansion of the European Union, the number of languages that may need
      to be translated has increased to 21, and there is the potential for many more.
      This article suggests how to tackle translation.

PMID- 16438450
TI  - Heparin conjugate: a versatile tool to modify surfaces.
AB  - Heparin is well known for its ability to improve the blood compatibility of
      materials. A method that uses a macromolecular conjugate of heparin to modify
      artificial and biological surfaces is described here.

PMID- 16438451
TI  - Manufacturing in China.
AB  - China offers advantages, but establishing production facilities in the country is
      complex. This article reports one company's observations on operating there.

PMID- 16438452
TI  - Update in hypertension: the Seventh Joint National Committee report and beyond.
AB  - The Seventh Report of the Joint National Committee on Prevention, Detection,
      Evaluation on and Treatment of High Blood Pressure (JNC-VII) had new key messages
      that need to be highlighted for practicing physicians. More than two years has
      elapsed since its publication and several important trials and meta-analyses were
      published during this period. Most of these publications supported and reinforced
      the JNC-VII recommendations, but others did not fully agree. Thus, some questions
      have arisen that need to be addressed in future research. This review will
      discuss what is new in JNC-VII and post-JNC-VII evidence that supports or
      disputes the recommendations. In addition, the results of other significant
      trials will be addressed. Finally, we outline the clinical "bottom line" and
      emphasize the practical application of this evidence.

PMID- 16438454
TI  - The pattern of dysphagia in children.
AB  - BACKGROUND: Difficulty in swallowing is not uncommon among children and yet
      little information is available in the literature. We report our experience on
      the pattern of this condition. METHODS: We extracted data from the medical
      records of 42 children with dysphagia on age at presentation, nationality,
      gender, and final diagnosis. RESULTS: From 1993 to 2002, 96% of 42 children
      presenting with dysphagia were Saudi nationals, ranging in age from 3 months to
      18 years, with a male to female ratio of 1:0.6. An etiologic diagnosis was found
      in 30 children (72%). Esophagitis, esophageal strictures and motility disorders
      were the most common causes of dysphagia, occurring in 16 (38%), 7 (17%), and 4
      (10%) children, respectively. Two children had esophageal webs and one had an
      esophageal ring. Age-related analysis indicated that most of the cases of
      esophagitis (11/16, 69%) and strictures (5/7, 71%) occurred in young children
      whereas most nondemonstrable causes occurred in older children (9/12, 75%).
      CONCLUSION: This report documents a pattern of dysphagia in Saudi Arab children
      that is similar to descriptions from other countries.

PMID- 16438453
TI  - Incidence of musculoskeletal pain in adult Kuwaitis using the validated Arabic
      version of the WHO-ILAR COPCORD Core Questionnaire.
AB  - BACKGROUND: The WHO-ILAR Community Oriented Program for Control of Rheumatic
      Diseases (COPCORD) primarily aims to estimate the burden of musculoskeletal
      symptoms/disorders. We estimated the incidence of musculoskeletal pain in the
      first community-based COPCORD study in Kuwait SUBJECTS AND METHODS: The validated
      Arabic version of the WHO-ILAR COPCORD Core Questionnaire was used in a survey of
      2500 randomly selected Kuwaiti households to assess the frequency of
      musculoskeletal pain, disability, and health-seeking behavior in adult Kuwaitis.
      Those subjects reporting no musculoskeletal pain were identified and followed-up
      for a period of one year by contacting them every 2 weeks. Once a respondent
      reported pain, an appointment to report to hospital was offered and the subject
      was examined by a rheumatologist using American College of Rheumatology (ACR)
      criteria. RESULTS: Of 5159 adults who were non-complainers in an earlier
      prevalence phase of the study, 3341 responded to phone calls (response rate of
      65%). The incidence of musculoskeletal pain was 6.6% (95% CI, 3.4%-9.7%) Age- and
      sex-adjusted incidence rates were 7.2% (95% CI, 3.4%-10.5%) for females and 6.1%
      (95% CI, 3.1%-9.2%) for males. The incidence rate increased with increasing age,
      body mass index, and with being married. The common sites of pain were knee, low
      back and shoulder. CONCLUSION: The incidence of musculoskeletal pain among
      Kuwaiti adults is reported for the first time. Further studies adopting the same
      instrument in other communities are warranted to compare with our findings.

PMID- 16438455
TI  - Predictive value of thyroid hormones on the first day in adult respiratory
      distress syndrome patients admitted to ICU: comparison with SOFA and APACHE II
      scores.
AB  - BACKGROUND: Thyroid hormone dysfunction could affect outcome and increase
      mortality in critical illness. Therefore, in a prospective, observational study
      we analyzed and compared the prognostic accuracy of free tri-iodothyronine (fT3),
      free thyroxine (fT4), thyroid-stimulating hormone (TSH), along with the APACHE II
      and SOFA scoring systems in predicting intensive care unit (ICU) mortality in
      critically ill patients. PATIENTS AND METHODS: Physiology scores were calculated
      for the first 24 hours after ICU admission in 206 patients with acute respiratory
      distress syndrome. APACHE II and SOFA scores were employed to determine the
      initial severity of illness. Thyroid hormones were measured within the first 24
      hours. Logistic regression models were created for APACHE II scores, SOFA scores,
      and thyroid hormone levels. The models predicted high- and low-risk subgroups.
      Models that showed a good fit were stratified by Kaplan-Meier survival curves.
      RESULTS: There were 98 (47.6%) survivors and 108 (52.4%) non-survivors. The
      survivors had a lower APACHE II score (11.50 vs 15.82, P < 0.0005), a lower SOFA
      score (6.06 vs 9.42, P < 0.0005), a younger age (57 vs 70 years, P = 0.008), a
      shorter ICU stay (13 vs 16 days, P = 0.012), and a higher fT3 level (2.18 vs 1.72
      pg/mL, P = 0.002) than non-survivors. ICU survival was most closely predicted by
      a model that included age and fT3 and a model that included APACHE II and APACHE
      II*sex. CONCLUSION: In critically ill patients, serum fT3 concentrations markedly
      decreased after ICU admission among non-survivors. According to our findings, fT3
      levels might have additive discriminatory power to age, SOFA and APACHE II scores
      in predicting short-term mortality in ARDS patients admitted to ICU.

PMID- 16438456
TI  - Acetylator phenotype in Iraqi patients with allergic contact dermatitis.
AB  - BACKGROUND: Few studies have been done on acetylator status in ACD. This study
      determined acetylator status in Iraqi patients with allergic contact dermatitis
      (ACD) in comparison to a matched control group. PATIENTS AND METHODS: The study
      included 35 ACD patients and 67 healthy volunteers. The ACD patients were
      diagnosed clinically and the diagnosis was confirmed by patch test. A detailed
      history wastaken from the patients. After an overnight fast, each control subject
      and each patient received a single oral dose of 100 mg of dapsone. A blood sample
      was collected after 3 hours and plasma was separated for determiination of
      dapsone and monoacetyldapsone by HPLC. RESULTS: Twenty-six of the 35 ACD patients
      returned for follow up. The frequency of slow acetylators in healthy individuals
      was 71.6%, while the frequency of rapid acetylators was 28.4%. The frequency of
      slow acetylators in ACD patients was 60.0% while the frequency of rapid
      acetylators was 40.0%. There was no association between the acetylator status,
      personal history of allergy, patch-test positivity or sites of dermatitis in ACD
      patients. CONCLUSION: A rapid acetylator status might predispose to ACD, but does
      not seem to influence other features of the disease.

PMID- 16438457
TI  - Insulinoma in Iran: a 20-year review.
AB  - BACKGROUND: The time between onset of symptoms of insulinoma to diagnosis ranges
      from 10 days to more than 20 years. To help physicians make an earlier diagnosis,
      we defined the clinical, imaging and paraclinical characteristics of insulinoma
      in cases from seven referral hospitals in Iran over two decades. METHODS: The
      medical records of 68 cases with biochemical or histological evidences of
      insulinoma were reviewed. RESULTS: More males were affected (53%). The mean age
      at diagnosis was 39 +/- 15.3 years. The mean duration of symptoms was 39.9 +/-
      59.3 months. Eighty-four percent of patients had been initially misdiagnosed as
      cereberovascular accident (CVA), epilepsy, conversion disorder, and others).
      Neuroadrenergic symptoms were observed in 89.6% and and neuroglycopenic symptoms
      in 97% of patients. Mean diameter of tumours was 2.9 cm (range, 1 cm to 8.5 cm).
      Of 52 pathologically confirmed cases of insulinoma, 43 tumours (87.8%) were
      single and 49 (94.2%) were benign. Fifty-five patients had undergone surgery,
      with a successful outcome in 44 (80%). CONCLUSION: The high incidence of
      neuroglycopenic symptoms suggest the clinical impression of insulinoma when
      patients present with a suggestive clinical syndrome. The clinical impression is
      essential to decrease the frequent delay in the diagnosis of insulinoma.

PMID- 16438458
TI  - Acute effects of lobectomy on right ventricular ejection fraction and mixed
      venous oxygen saturation.
AB  - BACKGROUND: Traditional methods of assessing the operative risk for lung
      resection provide only a modest ability to predict postoperative morbidity and
      mortality. The aim of this study was to evaluate the effect of lobectomy on
      pulmonary hemodynamic and gas exchange variables using the RV thermodilution
      ejection fraction/oximetric catheter. METHODS: We evaluated the acute
      postoperative effects of lung resection on hemodynamic and gas exchange
      parameters in 30 patients. Anesthesia was induced with thiopentone sodium and
      maintained with midazolam, fentanyl and pipecuronium. Intubation was performed
      with a double-lumen, left-sided endobronchial tube for one lung ventilation. The
      hemodynamic and gas exchange parameters were recorded before and after induction
      of anesthesia, and two hours after lung resection. These parameters were also
      recorded after the classification of the patients according to the underlying
      lung pathology. RESULTS: Lobectomy was associated with significant hemodynamic
      changes and good maintenance of gas exchange variables. SVI, LVSWI and RVEF were
      significantly decreased in the early postoperative period after lung resection.
      MPAP, COP, CI, SVRI, PVRI, RVSWI, and RVEDVI showed no significant changes during
      the perioperative period. SVO2 showed a significant increase after lung resection
      when compared with preinduction values, while VO2 significantly decreased. SaO2,
      a-A PO2, QS-QT, DO2, and O2ER showed no significant changes during the
      perioperative period. CONCLUSIONS: We conclude that in the acute post-resection
      period (up to 2 hours postoperatively) there is right and left ventricular
      dysfunction with good maintenance of gas exchange.

PMID- 16438459
TI  - Transcranial Doppler ultrasound assessment of intracranial hemodynamics in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Diabetics have a 3-fold risk for cardiovascular diseases compared
      with non-diabetics. This study was designed to evaluate cerebral hemodynamic
      changes related to type 2 diabetes mellitus (DM) with transcranial Doppler
      ultrasonography (TCD). TCD is a highly sensitive and specific method of quick
      bedside assessment of cerebrovascular circulation hemodynamics. PATIENTS AND
      METHODS: In a prospective study, we compared a group of 100 patients with the
      diagnosis of type 2 diabetes mellitus (aged 48 to 67 years) and an age- and sex
      matched control group of 100 healthy subjects without diabetes mellitus. We
      measured flow velocities (Vm) and the Gosling pulsatility index (PI) of the
      middle cerebral artery (MCA). RESULTS: The rate of TCD abnormalities was
      significantly higher in diabetic patients than in healthy control subjects (55%
      vs. 11%, P < 0.05). The PI was significantly higher in diabetic patients than in
      healthy controls (P < 0.001). Atherosclerotic changes were found in 34.0% and
      71.4% of patients suffering from diabetes for <5 and > or =5 years, respectively.
      CONCLUSION: This study suggests that TCD is a useful marker for the detection of
      diabetic cerebrovascular changes. The duration and type of diabetes were found to
      have an impact on the development of pathologic cerebrovascular changes.

PMID- 16438460
TI  - Serum prolactin and migraine.

PMID- 16438461
TI  - Management of blunt hepatic and splenic trauma in children.

PMID- 16438462
TI  - Two unusual hematologic presentations of tuberculosis.

PMID- 16438464
TI  - Abdominal aneurysms in Behcet's Disease.

PMID- 16438463
TI  - Diffuse panbronchiolitis, a potentially misdiagnosed sinopulmonary syndrome.

PMID- 16438465
TI  - Respiratory arrest after low-dose fentanyl.

PMID- 16438466
TI  - A 33-year-old male with a chest lesion on a routine chest radiograph. Pulmonary
      arteriovenous malformation (PAVM).

PMID- 16438467
TI  - RE: Pulmonary edema complicating ovarian hyperstimulation syndrome: low-pressure
      edema, high-pressure edema, or mixed edema?

PMID- 16438468
TI  - Comparison of smear cytology and cell blocks in detection of respiratory cancer.

PMID- 16438469
TI  - RE: Non-traumatic cerebrospinal fluid rhinorrhea: diagnosis and management.

PMID- 16438470
TI  - Stalled Deficit Reduction Act thwarts physician payments and program funding.

PMID- 16438471
TI  - Industry leaders support LTC reform for flawed system.

PMID- 16438472
TI  - Calcific uremic arteriolopathy (calciphylaxis).

PMID- 16438473
TI  - A cluster study of predictors of severe West Nile virus infection.
AB  - OBJECTIVE: To assess the value of multifocal chorioretinitis and of clinical
      manifestations and biologic parameters in the diagnosis of West Nile virus (WNV)
      infection. PATIENTS AND METHODS: We conducted a prospective, controlled case
      series study during an outbreak of WNV infection between August 15 and October
      24, 2003, of 64 consecutive patients who presented with clinical manifestations
      consistent with WNV disease. In each patient, standardized clinical and biologic
      data were collected. An ophthalmologic examination searching particularly for
      multifocal chorioretinitis was performed. RESULTS: Of 64 patients who presented
      primarily with meningitis and/or encephalitis, 36 had IgM antibodies against WNV.
      The WNV-infected patients tended to be older (median age of 54 years vs 46 years
      in WNV infection and control groups, respectively) and more frequently had
      diabetes (30% vs 7% in WNV infection and control groups, respectively; P = .03).
      Multifocal chorioretinitis was found in 75% of WNV-infected patients but in no
      patient in the control group (P = .001). Blood glucose and amylase levels were
      higher in WNV-infected patients, whereas serum sodium levels were lower. The
      cerebrospinal fluid leukocyte count and protein levels were significantly higher
      in WNV meningitis or encephalitis. Overall, multifocal chorioretinitis had 100%
      specificity and 73% sensitivity (88% when only patients with meningitis or
      encephalitis were analyzed) for the diagnosis of WNV. Multivariate analysis
      disclosed multifocal chorioretinitis as the only predictor of WNV infection (odds
      ratio, 62; 95% confidence interval, 6-700; P = .001). CONCLUSION: Multifocal
      chorioretinitis appears to be a specific marker of WNV infection, particularly in
      patients who present with meningoencephalitis. An ophthalmologic examination
      should be part of the routine evaluation of such patients.

PMID- 16438474
TI  - Ropinirole in the treatment of patients with restless legs syndrome: a US-based
      randomized, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To assess the efficacy, safety, and tolerability of the dopamine
      agonist ropinirole in the treatment of patients with moderate to severe primary
      restless legs syndrome (RLS). PATIENTS AND METHODS: This multicenter, 12-week,
      double-blind, placebo-controlled, flexible-dose study enrolled US patients and
      was conducted between September 2003 and May 2004. Patients were randomized to
      ropinirole or placebo, 0.25-4.0 mg as needed and tolerated, once daily, 1 to 3
      hours before bedtime. The primary end point was mean change from baseline to week
      12 in International Restless Legs Scale (IRLS) total score. Key secondary
      efficacy measures included the Clinical Global Impression-Improvement scale.
      RESULTS: A total of 381 patients were enrolled; 164 (87.7%) of 187 patients
      randomized to ropinirole and 167 (86.1%) of 194 randomized to placebo completed
      the study. Significant treatment differences favoring ropinirole, compared with
      placebo, were observed for change in IRLS total score at week 12 (adjusted mean
      treatment difference, -3.7; 95% confidence interval, -5.4 to -2.0; P < .001) and
      for all 3 key secondary end points: mean change from baseline in IRLS total score
      at week 1 and proportion of patients who were much/very much improved on the
      Clinical Global Impression Improvement scale at weeks 1 and 12. Ropinirole was
      associated with significantly greater Improvements in subjective measures of
      sleep disturbance, quantity, and adequacy; quality of life; and anxiety. Although
      treatment differences favoring ropinirole in daytime somnolence were observed,
      they were not statistically significant (P = .10). Ropinirole was generally well
      tolerated, with an adverse-event profile consistent with other dopamine agonists.
      CONCLUSION: This study confirms that ropinirole improves RLS symptoms and
      subjective measures of sleep, quality of life, and anxiety and that it is
      generally well tolerated.

PMID- 16438475
TI  - Associations between the hospitalist model of care and quality-of-care-related
      outcomes in patients undergoing hip fracture surgery.
AB  - OBJECTIVE: To investigate the relationship between the hospitalist consultant
      model of care and both length of hospital stay (LOS) and hospital cost for
      patients undergoing hip fracture surgery. PATIENTS AND METHODS: We
      retrospectively studied 118 consecutive patients admitted with hip fracture
      (diagnosis related groups 79.35 and 81.52) between January 1, 2002, and December
      31, 2002, at a community-based academic medical center. For each patient,
      consultations for preoperative medical evaluation and management of postoperative
      complications were performed by a hospitalist or a traditional medical consultant
      (nonhospitalist). We defined "hospitalist" as dedicated hospital-based physicians
      who provide their maximum professional time in inpatient health care delivery and
      who are completely free of outpatient responsibilities. Time to consultation
      (TTC), time to surgery (TTS), LOS, and total hospital costs were determined for
      each patient by review of the medical records and were compared between
      hospitalist and nonhospitalist consultants. RESULTS: Both TTC and TTS were
      significantly lower for hospitalist patients (P < .001 and P = .004,
      respectively). Although not statistically significant, cost and LOS also were
      lower for patients receiving hospitalist care. In the hospitalist group, median
      cost was an estimated dollar 1777 less, and median LOS was 1 day less than in the
      nonhospitalist group. CONCLUSION: Hospitalist Involvement in the medical
      management of patients undergoing hip fracture surgery may be associated with
      decreases in TTC, TTS, LOS, and total hospital cost. The results of this study
      have implications for consultative medical care of patients undergoing urgent
      surgery and their health outcomes.

PMID- 16438476
TI  - Suspected ventilator-associated pneumonia in cardiac patients admitted to the
      coronary care unit.
AB  - OBJECTIVE: To determine the incidence, risk factors, associated pathogens, and
      outcome of ventilator-associated pneumonia (VAP) in patients admitted to a
      coronary care unit (CCU). PATIENTS AND METHODS: This retrospective cohort study
      was performed in the CCU of a single tertiary medical center. Patients who were
      admitted to the CCU between March 23, 2002, and May 25, 2003, and who required
      invasive mechanical ventilation for more than 48 hours were included. RESULTS: Of
      the 92 patients who met the study criteria, 17 (18.5%; 95% confidence interval,
      11.9%-27.6%) developed VAP. The incidence of VAP was 36.3 (95% confidence
      interval, 21.1-58.1) per 1000 days of mechanical ventilation. There were no
      statistically significant differences in demographics, presence of chronic
      obstructive pulmonary disease, or use of continuous intravenous sedatives or
      neuromuscular blockers between patients with and without VAP. The most commonly
      isolated organisms were methicillin-sensitive Staphylococcus aureus, Sphingomonas
      paucimobilis, and Stenotrophomonas maltophilia. The median length of stay in the
      CCU for patients with VAP was 10 days compared to 6 days for patients without VAP
      (P < .01). Eight (47%) of the 17 patients with VAP died compared to 29 (39%) of
      75 patients without VAP (P = .52). CONCLUSIONS: The incidence of VAP in the CCU
      is similar to or higher than that reported in other intensive care units. The
      development of VAP in CCU patients is associated with a prolonged CCU stay but
      not with an increased hospital mortality.

PMID- 16438477
TI  - Snowmobile injuries in children and adolescents.
AB  - OBJECTIVE: To characterize the risk factors and patterns of injury for children
      involved in snowmobile incidents. PATIENTS AND METHODS: We reviewed the medical
      records of patients younger than 18 years who required hospital admission for
      snowmobile-related incidents from 1992 to 2001. Information obtained from these
      records and from the trauma database included patient demographics, mechanism of
      injury, injury patterns, medical care, and outcomes. RESULTS: Forty-three
      patients were admitted to our hospital for snowmobile-related incidents.
      Snowmobile incidents occurred most commonly in male adolescents. The 2 most
      common mechanisms of injury were ejection and striking a stationary object.
      Twenty-seven (63%) of the patients drove the snowmobile. Only 23 patients (53%)
      wore a helmet. At presentation, the mean +/- SEM Injury Severity Score (ISS) was
      12.1 +/- 1.4. Orthopedic injuries predominated (n = 42); however, abdominal (n =
      12) and head (n = 8) injuries were also common. Four patients were intubated, and
      15 required intensive care unit admission. Twenty-nine patients (67%) required
      surgical intervention. The mean +/- SEM length of hospitalization was 6.7 +/- 1.4
      days. No deaths occurred; however, 7 patients (16%) had long-term disabilities. A
      significant improvement occurred in both Glasgow Coma Scale (GCS) score and ISS
      for patients using a helmet. In addition, helmet use increased with age (P =
      .01). Days in the intensive care unit were proportional to both GCS score (r(s) =
      -0.47; P = .002) and ISS (r(s) = 0.6; P < .001). Length of hospitalization also
      correlated with both GCS score (r(s) = -0.03; P = .008) and ISS (r(s) = 0.54; P =
      .02). CONCLUSION: Snowmobiles are a significant source of multitrauma for
      children. Orthopedic injuries predominate, especially in older children, and can
      lead to long-term disabilities. Helmet use significantly reduces injuries;
      however, vulnerable younger patients do not frequently wear helmets.

PMID- 16438478
TI  - Comparison of electrophysiologic monitors with clinical assessment of level of
      sedation.
AB  - OBJECTIVE: To assess the correlation between 2 clinical sedation scales and 2
      electroencephalographic (EEG)-based monitors used during surgical procedures that
      required mild to moderate sedation. PATIENTS AND METHODS: Patients scheduled for
      elective surgery participated in this Institutional review board-approved study
      from March 2003 to February 2004. Level of sedation was determined both
      clinically using the Ramsay and the Observer's Assessment of Alertness/Sedation
      scales and with 2 EEG measures (the Bispectral Index version XP [BIS XP] or the
      Patient State Analyzer [PSA 4000]). Correlation between these 2 measures of
      sedation were tested using nonparametric statistical tests. RESULTS: The BIS XP
      monitor was used in 26 patients, and the PSA 4000 monitor was used in 24
      patients. The Ramsay and Observer's Assessment of Alertness/Sedation scores
      correlated with each other (r = -0.96; P < .001) and with both the BIS XP (r = 
      0.89 and r = 0.91, respectively; P < .001) and the PSA 4000 (r = -0.80 and r =
      0.80, respectively; P < .001) values. However, this correlation was strongest
      only at the extremes. Between the BIS XP and PSA 4000 values of 61 and 80, the
      clinical sedation scores varied greatly. CONCLUSION: On the basis of our results,
      these EEG-based monitors cannot reliably distinguish between light and deep
      sedation.

PMID- 16438479
TI  - Angiotensin-converting enzyme inhibitors and obstructive sleep apnea.
AB  - Angiotensin-converting enzyme (ACE) inhibitors may induce cough and
      rhinopharyngeal inflammation. Obstructive sleep apnea (OSA) is characterized by
      upper airway inflammation. We describe a patient who, during enalapril treatment,
      developed cough, upper airway symptoms, and diurnal sleepiness, with an increased
      number of obstructive apnea-hypopnea episodes (apnea-hypopnea index [AHI], 25)
      during sleep. Her symptoms and AHI improved 1 month after enalapril was
      discontinued and diuretic therapy (hydrochlorothiazide-spironolactone) was
      initiated. Similar findings were observed in 4 other patients with OSA who had
      ACE inhibitor-induced cough. The mean +/- SD AHI was 33.8+/-21.0 during enalapril
      treatment and 20.0+/-17.0 after withdrawal of this drug (P = .04). Exhaled nitric
      oxide, a marker of airway inflammation, was increased during enalapril treatment
      (15.0 +/- 4.3 parts per billion) and decreased after discontinuation of this drug
      (9.0 +/- 2.6; P = .03). No significant difference in the AHI and exhaled nitric
      oxide was observed in 4 patients with OSA who did not experience cough, before or
      after withdrawal of ACE inhibitor treatment. These findings suggest that ACE
      inhibitor treatment may contribute to OSA by inducing upper airway inflammation.

PMID- 16438480
TI  - Platelets in atherothrombosis.
AB  - Atherosclerosis is a diffuse, systemic disease that affects the coronary,
      cerebral, and peripheral arterial trees. Disruption of atherosclerotic plaques
      leads to thrombus formation and arterial occlusion. This unpredictable and
      potentially life-threatening atherothrombotic sequence underlies clinical events
      such as angina, myocardial infarction, transient ischemic attacks, and stroke.
      One of the key components of a clot is the platelet. Although it was previously
      thought that platelets were relatively inactive cells that merely provided a
      framework for the attachment of other cells and proteins to mechanically stop
      bleeding due to injury, it is now known that this is not the case. Platelets
      secrete and express a large number of substances that are crucial mediators of
      both coagulation and inflammation. This article reviews the centrality of the
      platelet in atherothrombosis and briefly looks at the efficacy of antiplatelet
      agents in preventing and treating cardiovascular disease.

PMID- 16438481
TI  - A look between the cardiomyocytes: the extracellular matrix in heart failure.
AB  - The extracellular matrix (ECM) of the heart dynamically interacts with various
      cellular components of the myocardium, including the myocytes and connective
      tissue cells. With the development and progression of heart failure, left
      ventricular (LV) myocardial remodeling occurs. The progression of LV remodeling
      is accompanied by alterations in the structure and function of the ECM that occur
      after injury resulting from neurohormonal activation, changes in LV loading
      conditions, and alterations in myocardial perfusion and metabolism and is
      secondary to a host of nonmyocyte signaling pathways that affect repair and
      remodeling of the myocardium as a whole. This article attempts to review some of
      these processes and their interactions and to provide a focus to the often
      overlooked contribution of the ECM to the development and progression of heart
      failure and thereby its potential role as a target for therapy for heart failure.

PMID- 16438482
TI  - Methamphetamine abuse: a perfect storm of complications.
AB  - Previously restricted primarily to Hawaii and California, methamphetamine abuse
      has reached epidemic proportions throughout the United States during the past
      decade, specifically in rural and semirural areas. Particular characteristics of
      methamphetamine production and use create conditions for a "perfect storm" of
      medical and social complications. Unlike imported recreational drugs such as
      heroin and cocaine, methamphetamine can be manufactured locally from commonly
      available household ingredients according to simple recipes readily available on
      the Internet. Methamphetamine users and producers are frequently one and the
      same, resulting in both physical and environmental consequences. Users experience
      emergent, acute, subacute, and chronic injuries to neurologic, cardiac,
      pulmonary, dental, and other systems. Producers can sustain life-threatening
      injuries in the frequent fires and explosions that result when volatile chemicals
      are combined. Partners and children of producers, as well as unsuspecting first
      responders to a crisis, are exposed to toxic by-products of methamphetamine
      manufacture that contaminate the places that serve simultaneously as "lab" and
      home. From the vantage point of a local emergency department, this article
      reviews the range of medical and social consequences that radiate from a single
      hypothetical methamphetamine-associated incident.

PMID- 16438483
TI  - 33-year-old woman with pleuritic chest pain and nonproductive cough.

PMID- 16438484
TI  - Giant cell arteritis and spinal cord compression: an overlap syndrome?
AB  - We describe 2 patients with spinal cord compression that occurred in the course
      of biopsy-proven giant cell arteritis (GCA). One case was due to an epidural
      tumorlike inflammatory lesion, the other to a concentric inflammatory thickening
      of the meninges. Both patients were highly corticodependent; they had low-titer
      anti-neutrophil cytoplasmic antibodies but no antimyeloperoxidase or
      antiproteinase 3 autoantibodies. The diagnosis was established by surgical
      biopsy. The histological pattern was reminiscent of Wegener granulomatosis. Both
      patients experienced relapse, despite high doses of corticosteroids, and
      experienced remission after the introduction of cyclophosphamide. Intravenous
      immunoglobulin perfusions were added for 1 patient. To our knowledge, spinal cord
      compression by a spinal pseudotumor or inflammatory meningitis has not been
      reported in the course of GCA. An overlap syndrome between GCA and Wegener
      granulomatosis is discussed.

PMID- 16438485
TI  - Genetics of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder of unknown cause
      with variable clinical expression. About 70% of patients are women. Genetic
      factors play an important role and likely account for about 60% of disease
      susceptibility and expression. The association with the HLA-DRB1 gene is the best
      understood, although several non-HLA loci have been linked to RA, including the
      18q21 region of the TNFRSR11A gene, which encodes the receptor activator of
      nuclear factor kappaB, important in bone resorption in RA. Genetic factors are
      also important in the treatment of RA because the activity of enzymes relevant in
      the metabolism of drugs such as methotrexate and azathioprine, including
      methylenetetrahydrofolate reductase and thiopurine methyltransferase, are in part
      genetically determined.

PMID- 16438486
TI  - The myelodysplastic syndromes: diagnosis and treatment.
AB  - The myelodysplastic syndromes (MDSs) are common, acquired, clinically challenging
      hematologic conditions that are characterized by bone marrow failure and a risk
      of progression to acute leukemia. These disorders can arise de novo, especially
      in elderly patients or, less often, as a consequence of prior chemotherapy or
      radiotherapy for an unrelated disease. The MDS classification systems were
      revised recently and updated. These refined classification and prognostic schemes
      help stratify patients by their risk of leukemia progression and death; this
      knowledge can help clinicians select appropriate therapy. Although many
      treatments for MDS have been proposed and evaluated, at present, only
      hematopoietic stem cell transplantation offers any real hope for cure, and no
      available therapy beyond general supportive care offers benefit to more than a
      minority of patients. However, recent clinical trials enrolling patients with MDS
      have reported encouraging results with use of newer drugs, including
      lenalidomide, decitabine, and darbepoetin alfa. Other exciting treatment regimens
      are being tested. Here, we present a contemporary, practical clinical approach to
      the diagnosis and risk-stratified treatment of MDS. We review when to suspect
      MDS, detail how to evaluate patients who may have a form of the condition,
      explain key features of treatments that are currently available in the United
      States, and summarize a general, common-sense therapeutic approach to patients
      with MDS.

PMID- 16438487
TI  - Open heart surgery and the Mayo Clinic.

PMID- 16438488
TI  - Backpack therapy.

PMID- 16438489
TI  - Backpack therapy.

PMID- 16438490
TI  - "Myelodysplasia," myeloneuropathy, and copper deficiency.

PMID- 16438491
TI  - Screening for adenocarcinoma of the prostate.

PMID- 16438492
TI  - Botulinum toxin for headache.

PMID- 16438493
TI  - Patients' lack of knowledge of their medications and diagnosis at discharge.

PMID- 16438494
TI  - Sulfur radical cations. kinetic and product study of the photoinduced
      fragmentation reactions of (phenylsulfanylalkyl)trimethylsilanes and
      phenylsulfanylacetic acid radical cations.
AB  - Laser and steady-state photolysis, sensitized by NMQ+, of PhSCH(R)X 1-4 (R = H,
      Ph; X =SiMe3, CO2H) was carried out in CH3CN. The formation of 1+*-4+* was
      clearly shown. All radical cations undergo a fast first-order fragmentation
      reaction involving C-Si bond cleavage with 1+* and 2+* and C-C bond cleavage with
      3+* and 4+*. The desilylation reaction of 1+* and 2+* was nucleophilically
      assisted, and the decarboxylation rates of 3+* and 4+* increased in the presence
      of H2O. A deuterium kinetic isotope effect of 2.0 was observed when H2O was
      replaced by D2O. Pyridines too were found to accelerate the decarboxylation rate
      of 3+* and 4+*. The rate increase, however, was not a linear function of the base
      concentration, but a plateau was reached. A fast and reversible formation of a H
      bonded complex between the radical cation and the base is suggested, which
      undergoes C-C bond cleavage. It is probable that the H-bond complex undergoes
      first a rate determining proton-coupled electron transfer forming a carboxyl
      radical that then loses CO2. The steady-state photolysis study showed that PhSCH3
      was the exclusive product formed from 1 and 3 whereas [PhS(Ph)CH-]2 was the only
      product with 3 and 4.

PMID- 16438495
TI  - Theoretical and experimental studies on the Baeyer-Villiger oxidation of ketones
      and the effect of alpha-halo substituents.
AB  - The Baeyer-Villiger reactions of acetone and 3-pentanone, including their
      fluorinated and chlorinated derivatives, with performic acid have been studied by
      ab initio and DFT calculations. Results are compared with experimental findings
      for the Baeyer-Villiger oxidation of aliphatic fluoro and chloroketones.
      According to theoretical results, the first transition state is rate-determining
      for all substrates even in the presence of acid catalyst. Although the
      introduction of acid into the reaction pathway leads to a dramatic decrease in
      the activation energy for the first transition state (TS), once entropy is
      included in the calculations, the enthalpic gain is lost. Of all substrates
      examined, pentanone reacts with performic acid via the lowest energy transition
      state. The second transition state is also lowest for pentanone, illustrating the
      accelerating effect of the additional alkyl group. Interestingly, there is only a
      small energetic difference in the transition states leading to migration of the
      fluorinated substituent versus the alkyl substituent in fluoropentanone and
      fluoroacetone. These differences match remarkably well with the experimentally
      obtained ratios of oxidation at the fluorinated and nonfluorinated carbons in a
      series of aliphatic ketones (calculated, 0.3 kcal/mol, observed, 0.5 kcal/mol),
      which are reported herein. The migration of the chlorinated substituent is
      significantly more difficult than that of the alkyl, with a difference in the
      second transition state of approximately 2.6 kcal/mol.

PMID- 16438496
TI  - Control of stereoselective protonation of enols1,2.
AB  - A decalyl framework with a siloxy enolic moiety and proximate proton transferring
      groups was synthesized. On enolate generation with fluoride two competitive
      reaction modes were possible: (a) intermolecular protonation, and (b)
      intramolecular proton transfer by the proximate group. Control of the protonation
      stereochemistry proved possible by varying the proximate group and by changing
      the acidity of the medium. With the groups -CH2OH, -CH=O, and -CH2OCH2OCH3 as the
      proximate groups, only intermolecular proton transfer was observed with no
      dependence on acidity. In contrast, with -COO- and COOH, only intramolecular
      protonation resulted but again with no dependence on acidity of the medium. In
      contrast, with -CH2NH2 as the proximate group, intramolecular proton transfer
      predominated with a dependence on the effective pH of the medium. A kinetic
      analysis provided a linear-log relationship of the ratio of the two stereoisomers
      with the medium acidity. The analysis revealed that two acetic acid molecules are
      involved in providing the proton to the enolate moiety. A theoretical analysis
      was developed paralleling the experimental results. In the ketonization
      transition state, the hybridization was shown to be close to sp2 hybridized at
      the alpha-enolate carbon.

PMID- 16438497
TI  - Nucleus-independent chemical shifts (NICS): distance dependence and revised
      criteria for aromaticity and antiaromaticity.
AB  - Nucleus-independent chemical shifts (NICS) have been used extensively for the
      identification of aromaticity properties of molecules, ions, intermediates, and
      transition states since their introduction in 1996 by Schleyer et al. Initially,
      probes (bq's) were placed at the centers of systems (NICS(0)) and later, 1A above
      the molecular planes (NICS(1)). However, contradicting assignments of aromaticity
      by NICS and other methods were found for some systems. In this article, an
      alternative NICS-based method is introduced. The method is based on scanning NICS
      values over a distance and separating them into in-plane and out-of plane
      contributions. The shapes of the plots of the chemical shifts and their
      components as a function of the distance of the NICS probe (bq) from the
      molecular plane give a clear indication of diamagnetic and paramagnetic ring
      currents. This method is applied to several (4n + 2)- and 4n pi-electron systems
      (molecules and ions) in the singlet and triplet electronic states, including some
      of the problematic systems mentioned above. It is also shown that relative
      aromaticities of rings in polycyclic systems (local aromaticities) cannot be
      estimated by comparing NICS or NICS-scan values.

PMID- 16438498
TI  - Synthesis of new nitrogen analogues of salacinol and deoxynojirimycin and their
      evaluation as glycosidase inhibitors.
AB  - The synthesis of two enantiomerically pure iminosugars, analogues of 1-L
      deoxynojirimycin (l-DNJ) and 1-D-deoxymannojirimycin (DMJ), was achieved using
      cyclic sulfate substituted isoxazoline derivatives. The piperidine ring was
      formed via the reduction of an isoxazoline into an amine which underwent a
      spontaneous intramolecular cyclization by reaction with the cyclic sulfate
      moiety. The nucleophilic attack of these two trisubstituted piperidines and
      morpholine on L- and D-erythritol-1,3-cyclic sulfates gave six new nitrogen
      analogues of salacinol. The inhibitory properties of the synthesized salacinol
      analogues were evaluated on several commercial glycosidases.

PMID- 16438499
TI  - Alkylthio unit as an alpha-pyrrole protecting group for use in dipyrromethane
      synthesis.
AB  - The synthesis of porphyrin precursors requires the successive introduction of
      substituents at the pyrrole alpha- and alpha'-positions (2- and 5-,
      respectively). An alpha-pyrrole substituent that serves as a temporary masking
      agent and is not deactivating would greatly facilitate such syntheses,
      particularly for beta-(3,4)-unsubstituted pyrroles, but has heretofore not been
      available. A series of alpha-RS groups (R = Me, Et, n-decyl, Ph) have been
      investigated in this regard, including the determination of the kinetics of
      substitution at the pyrrolic 3-, 4-, and 5-positions and the application to
      dipyrromethane formation. The RS group was readily introduced into the pyrrole
      alpha-position by the reaction of 2-thiocyanatopyrrole (prepared from pyrrole,
      ammonium thiocyanate, and iodine) and the corresponding Grignard reagent RMgBr.
      Each 2-alkylthio group activated the pyrrole ring toward deuteration at the 3- or
      5- (vs 4-) position. The dipyrromethane synthesis was carried out using a 2:1
      ratio of 2-(RS)pyrrole/benzaldehyde with a catalytic amount of InCl3 at room
      temperature in the absence of any solvent. The alpha-RS group was removed by
      hydrodesulfurization using Raney nickel or nickel complexes. This stoichiometric
      synthesis using the alpha-RS-protected pyrrole is in contrast to the traditional
      synthesis that employs an aldehyde and 25-100 mol equiv of pyrrole. Six meso
      substituted dipyrromethanes were prepared by the reaction of 2-(n
      decylthio)pyrrole/aldehyde/InCl3 (2.2:1:0.2 ratio) followed by
      hydrodesulfurization. Other reactions of the 1,9-bis(RS)dipyrromethane include
      oxidation to give (i) the 1,9-bis(RS)dipyrrin or (ii) the 1,9
      bis(RSO2)dipyrromethane, which underwent subsequent complexation with dibutyltin
      dichloride. In summary, under mild reaction conditions, the 2-alkylthio group is
      readily introduced to the pyrrole nucleus, directs electrophilic substitution to
      the 5-position, and is readily removed as required for elaboration of porphyrinic
      precursors.

PMID- 16438500
TI  - Mechanistic investigation of the isomerization of 5-vinyl-2-norbornene.
AB  - The isomerization reaction of 5-vinyl-2-norbornene (VNB) to 5-ethylidene-2
      norbornene (ENB) has been performed using a catalytic system consisting of an
      alkali metal hydride and an amine. Among various amines tested, only aliphatic
      1,2-diamines exhibited the activity for the isomerization. The isomerization was
      also affected by the alkali metal hydride employed. The activity of the alkali
      metal hydride increased with the increasing size of alkali metal: KH > NaH > LiH.
      A series of electron paramagnetic resonance (EPR) and UV-vis experiments on the
      active species suggest that the isomerization of VNB proceeds through a radical
      mechanism.

PMID- 16438501
TI  - Solvent effect on the alpha-effect: ground-state versus transition-state effects;
      a combined calorimetric and kinetic investigation.
AB  - In a study of the solvent effect on the alpha-effect, second-order rate constants
      (kNu-) have been determined spectrophotometrically for reactions of a series of
      substituted phenyl acetates with butan-2,3-dione monoximate (Ox-, alpha
      nucleophile) and p-chlorophenoxide (p-ClPhO-, reference nucleophile) in DMSO-H2O
      (DMSO = dimethyl sulfoxide) mixtures of varying compositions at 25.0 +/- 0.1
      degrees C. The magnitude of the alpha-effect, kOx-/kp-ClPhO-, increases as the
      DMSO content in the medium increases up to 40-50 mol %, reaching 500, one of the
      largest alpha-effect values, and then decreases on further addition of DMSO,
      resulting in a bell-shaped alpha-effect profile regardless of the nature of the
      substrates. The magnitude of the alpha-effect is found to be significantly
      dependent on the substrates (or, more quantitatively, on beta(nuc)). Thus,
      beta(nuc) is an important predictor of the magnitude of the alpha-effect. The
      bell-shaped alpha-effect profile found in the present system is attributed to the
      differential change in the sensitivity of the medium effect on the Ox- and p
      ClPhO- systems but not due to a change in the reaction mechanism or to a drastic
      change in the basicity of the two nucleophiles on addition of DMSO to the medium.
      Through application of calorimetric measurements of ground-state solvation
      combined with the diagnostic beta(nuc) values, it is shown that the transition
      state effect is more dominant than the ground-state effect as the origin of the
      alpha-effect in the present system.

PMID- 16438502
TI  - Synthesis and conformational analysis of 2'-fluoro-5-methyl-4'-thioarabinouridine
      (4'S-FMAU).
AB  - An improved synthesis of 2'-deoxy-2'-fluoro-5-methyl-4'-thioarabinouridine (4'S
      FMAU) is described. Participation of the 3'-O-benzoyl protecting group in the
      thiosugar precursor influenced the stereochemistry of the N-glycosylation
      reaction in nonpolar solvents, permitting a higher beta/alpha ratio than
      previously observed for similar Lewis acid catalyzed glycosylations.
      Conformational analysis of the nucleoside using 3JHH and 3JHF NMR coupling
      constants together with the PSEUROT program showed that it adopted a
      predominantly northern conformation in contrast to 2'-deoxy-2'-fluoro-5
      methylarabinouridine (FMAU), whose PSEUROT conformational analysis is presented
      here for the first time, which showed a dominantly southeast conformation. The
      sharp conformational switch attained by replacing the ring heteroatom is
      attributed to a decrease in relevant steric and stereoelectronic effects.

PMID- 16438503
TI  - Synthesis of the enediol isofurans, endogenous oxidation products of arachidonic
      acid.
AB  - Isofurans (IsoF's) are a new class of human arachidonic acid oxidation products.
      They are produced in vivo by a free radical mechanism, independent of the
      cyclooxygenase enzymes. These new compounds are available from natural sources
      only in microgram quantities as mixtures. The enantioselective preparation of two
      enediol isofurans, 15-epi-ent-SC-Delta13-8-IsoF and ent-SC-Delta13-8-IsoF, is
      described. A key transformation in the synthesis is the selective cascade
      cyclization of a diol epoxide benzenesulfonate to give the substituted
      tetrahydrofuran skeleton of the isofurans. This synthesis will make these
      metabolites available for physiological evaluation.

PMID- 16438504
TI  - Practical enantiospecific syntheses of lysobisphosphatidic acid and its
      analogues.
AB  - We describe a versatile, efficient, and practical method for the preparation of
      enantiomerically pure lysobisphosphatidic acid (LBPA), bisether analogues, and
      phosphorothioate analogues of LBPA from solketal. Phosphorylation of a protected
      sn-2-O-oleoyl glycerol with 2-cyanoethyl bis(N,N-diisopropylamino)phosphite,
      followed by oxidation and deprotection, generated the enantiomers of 2,2'-LBPA.
      The corresponding phosphorothioate analogues were obtained by oxidation with
      sulfur. The (R,R) and (S,S) enantiomers of both LBPA and phosphorothioate LBPA
      were synthesized from (S)- and (R)-solketal, respectively. The ether analogue of
      (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer were synthesized from
      the same enantiomer (S)-solketal by simply changing the sequence of deprotection
      steps.

PMID- 16438505
TI  - Synthesis of oligophenylene-substituted calix[4]crown-4s and their silver(I) ion
      induced nanocones formation.
AB  - A novel series of oligophenylene OPP(n)-substituted calix[4]crown-4s bearing up
      to three phenylene units, 1a-d, has been efficiently synthesized by means of
      either microwave-assisted or silver(I) ion-assisted Pd-catalyzed Suzuki cross
      coupling of tetraiodocalix[4]crown-4 and the corresponding oligophenylboronic
      acids. Complexation of OPP(n)-substituted calix[4]crown-4s with silver (I) ion
      was substantiated by 1H NMR spectroscopic and high-resolution ESI- or MALDI-TOF-
      MS studies. The weak binding affinities of OPP(n)-substituted calix[4]crown-4s
      for silver (I) ion, which were estimated from 1H NMR titrations with binding
      association in the range of 30-90 M(-1), allows reversible disassembling in the
      presence of KI at ambient temperature. Remarkably, the single-crystal X-ray
      structures of OPP(n)-calix[4]crown-4.Ag+ complexes indicate the atypical silver
      (I) ion-crown ether binding mode resulting in the formation of rigid nanocones
      with volume created up to approximately 1500 A(3). Our results suggested that
      despite the weak binding affinity of crown ether ligands for silver (I) ion, this
      weak interaction is still be useful as a tool to construct supramolecular
      architectures.

PMID- 16438506
TI  - E- or Z-selective Knoevenagel condensation of acetoacetic derivatives: effect of
      acylated substituent, that is, TEMPO and amines, as an auxiliary, and new
      accesses to trisubstituted E- and Z-2-alkenals and furans.
AB  - Knoevenagel condensation of O-acetoacetylTEMPOs (2,2,6,6-tetramethylpiperidine-1
      oxyl) with aldehydes substituted with an electron-withdrawing group such as
      aromatic and heteroaromatic ones leads preferentially to E-adducts, while
      acylacetoamides including Weinreb amides produce Z-adducts, exclusively. These E-
      and Z-adducts are selectively converted to the corresponding (2E)- and (2Z)-2
      hyroxyalkyl-2-alkenals, respectively, by stepwise reductions of the acyl group
      with DIBALH and then the carboxylic functions after protection of the hydroxy
      group. Transformation of the Knoevenagel products by taking advantage of the E
      geometry to trisubstituted furans is also developed.

PMID- 16438507
TI  - Ortho effect in the Bergman cyclization: interception of p-benzyne intermediate
      by intramolecular hydrogen abstraction.
AB  - Intramolecular hydrogen atom (H-atom) abstraction from the o-OCH3 group
      effectively intercepts the p-benzyne intermediate in the Bergman
      cycloaromatization of 2,3-diethynyl-1-methoxybenzene (1) before this intermediate
      undergoes either retro-Bergman ring opening or external H-atom abstraction. This
      process leads to the formation of a new diradical and renders the cyclization
      step essentially irreversible. Chemical and kinetic consequences of this
      phenomenon were investigated through the combination of computational and
      experimental studies.

PMID- 16438508
TI  - Ortho effect in the Bergman cyclization: comparison of experimental approaches
      and dissection of cycloaromatization kinetics.
AB  - Four different experimental sources of kinetic information were combined to study
      the effect of ortho substituents on the rate of Bergman cycloaromatization. All
      methods confirm that the cyclization barrier is highly sensitive to the nature of
      the ortho substituents. However, the measured activation energies strongly depend
      on the choice of experimental technique: even the relative trends provided by the
      different methods agree with each other only in the case of acceptor
      substituents. Both the onset peaks and the activation energies determined by
      differential scanning calorimetry (DSC; either in neat enediynes or in their
      solutions in 10.6 M 1,4-cyclohexadiene (1,4-CHD)) strongly overestimate the
      reactivity of 1,2-diethynylbenzene, suggesting that DSC cannot be taken as a
      reliable indicator of enediyne reactivity. This discrepancy is likely to stem
      from the presence of side reactions with low activation barriers, especially
      important when the reaction is conducted in neat enediyne. On the other hand,
      kinetic measurements based on monitoring the concentrations of enediyne reactants
      and naphthalene products provide reliable general trends that include the parent
      benzannelated enediyne. These measurements confirm that both ortho-NO2 and ortho
      CHO substituents substantially decrease activation energies for the Bergman
      cyclization, supporting earlier computational predictions. A comparison of theory
      and experiment suggests that computations at the Moeller-Plesset second-order
      perturbation theory (MP2)/6-31G level provide an excellent alternative to DFT
      when an accurate description of the contribution of noncovalent interactions to
      the activation energy is needed. Activation energies derived from k(eff), the
      effective rate constant under the pseudo-first-order approximation, depend on the
      1,4-CHD concentrations. The true rate constant, k(1), for the cyclization step
      and the ratio of constants for the retro-Bergman ring opening, k(-1), and the
      intermolecular H-atom abstraction, k2, were determined from the dependence of
      cycloaromatization kinetics of ortho- and para-NO2 substituted enediynes on the
      concentration of 1,4-CHD.

PMID- 16438509
TI  - New insights into the geometry of resorc[4]arenes: solvent-mediated
      supramolecular conformational and chiroptical control.
AB  - The conformations of inherently chiral resorc[4]arenes were studied by circular
      dichroism (CD) spectroscopy. Whereas in aprotic solvents the crown conformation
      (C4) is preferred, protic solvents favor the boat conformation (C2). As a result
      of electronic coupling of the lowest L(b) state of the resorcinol unit in the
      resorc[4]arene, the CD spectra show a strong dependence on the conformation of
      the macrocycle. For the first time the solvent dependence of the CD spectra was
      qualitatively analyzed and simulated by using theoretical methods. We have thus
      demonstrated not only that the conformation of the calixarene is dramatically
      manipulated by the solvent but also that the joint use of chiroptical
      measurements and theoretical calculations is a powerful and versatile tool for
      elucidating structural variations in supramolecular chemistry.

PMID- 16438510
TI  - CASPT2 study of the decomposition of nitrosomethane and its tautomerization
      reactions in the ground and low-lying excited states.
AB  - The dissociation reaction of nitrosomethane into methyl and nitric oxide and the
      tautomerization reactions to formaldehyde oxime, nitrone, and methoxy nitrene
      have been studied with the second-order multiconfigurational perturbation theory
      (CASPT2) by the computation of numerical energy gradients. The prevailing
      reactions in both the ground and the excited states are dissociations. The
      structures of the ground and excited states are compared with the corresponding
      complete active space SCF (CAS-SCF) geometries. It is found that changes in the
      individual bond lengths are rather large (0.01-0.02 A), while the character and
      energetics of the CASPT2 optimizations remain similar to the CAS-SCF values.

PMID- 16438511
TI  - Concise formal total synthesis of hybocarpone and related naturally occurring
      naphthazarins.
AB  - A concise formal total synthesis of the cytotoxic bisnaphthazarin derivative
      hybocarpone has been completed through the development of routes to the synthetic
      precursor, 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone. The
      oxidation of 3-ethyl-1,2,4,5,7,8-hexamethoxy-6-methylnaphthalene under Rapoport
      conditions gave 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone in
      modest yields after basic hydrolysis. In addition, treatment of 3-ethyl
      1,2,4,5,7,8-hexamethoxy-6-methylnaphthalene with boron tribromide provided access
      to the naturally occurring naphthazarin, boryquinone. The analogous oxidative
      demethylation of 3,6-dimethyl-1,2,4,5,7,8-hexamethoxynaphthalene and 3-ethyl
      1,2,4,5,7,8-hexamethoxynaphthalene resulted in the synthesis of 2,5,7,8
      tetrahydroxy-3,6-dimethyl-1,4-naphthoquinone (aureoquinone) and 3-ethyl-2,5,7,8
      tetrahydroxy-1,4-naphthoquinone, respectively. An alternative selective synthetic
      route to 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone was also
      developed utilizing an intramolecular Claisen condensation of methyl 2-butyryl
      3,5,6-trimethoxy-4-methylphenylacetate with concomitant in situ aerial oxidation.

PMID- 16438512
TI  - Further characterization of Mitsunobu-type intermediates in the reaction of
      dialkyl azodicarboxylates with P(III) compounds.
AB  - Structural characterization of compounds analogous to the proposed intermediates
      in the Mitsunobu esterification process is achieved by the combined use of NMR
      spectroscopy and X-ray diffractometric studies. The results show that compounds
      (t-BuNH)P(mu-N-t-Bu)(2)P[(N-t-Bu)(N-(CO(2)R)-N(H)(CO(2)R))] [R = Et (11), i-Pr
      (12)], obtained by treating [(t-Bu-NH)P-mu-N-t-Bu](2) (10) with
      diethylazodicarboxylate (DEAD) or diisopropylazodicarboxylate (DIAD),
      respectively, have a structure with the NH proton residing between the two
      nitrogen atoms ((P)N(t-Bu) and (P)N-N(CO(2)Et)); this is the tautomeric form of
      the expected betaine (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(NH-t-Bu)(N-(CO(2)R)-N(
      )(CO(2)R)]. Treatment of ClP(mu-N-t-Bu)(2)P[(N-t-Bu){N-(CO(2)-i-Pr)-N(H)(CO(2)-i
      Pr)] (6) with 2,6-dicholorophenol affords (2,6-Cl(2)-C(6)H(3)-O)P(mu-N-t
      Bu)(2)P(+)[(NH-t-Bu){N[(CO(2)i-Pr)(HNCO(2)i-Pr)]}](Cl(-))(2,6-Cl(2)-C(6)H(3)-OH)
      (14) that has a structure similar to that of (CF(3)CH(2)O)P(mu-N-t-Bu)(2)P(+)[(NH
      t-Bu){N[(CO(2)i-Pr)(HNCO(2)i-Pr)]}](Cl(-)) (13), but with an additional hydrogen
      bonded phenol. Both of these have the protonated betaine structure analogous to
      that of Ph(3)P(+)N(CO(2)R)NH(CO(2)R)(R'CO(2))(-) (2) proposed in the Mitsunobu
      esterification. Two other compounds, (ArO)P(mu-N-t-Bu)(2)P(+)(NH-t-Bu){N(CO(2)i
      Pr)(HNCO(2)i-Pr)}(Cl(-)) [Ar = 2,6-Me(2)C(6)H(3)O- (15) and 2-Me-6-t-Bu-C(6)H(3)
      O- (16)], are also prepared by the same route. Although NMR tube reactions of 11
      or 12 with tetrachlorocatechol, catechol, 2,2'-biphenol, and phenol revealed
      significant changes in the (31)P NMR spectra, attempted isolation of these
      products was not successful. On the basis of (31)P NMR spectra, the phosphonium
      salt structure (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(HN-t-Bu){N-(CO(2)R)
      N(H)(CO(2)R)](ArO(-)) is proposed for these. The weakly acidic propan-2-ol or
      water did not react with 11 or 12. Treatment of 12 with carboxylic acids/ p
      toluenesulfonic acid gave the products (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(HN-t-Bu){N
      (CO(2)-i-Pr)-N(H)(CO(2)-i-Pr)](ArCO(2)(-)) [Ar = Ph (18), 4-Cl-C(6)H(4)CH(2)
      (19), 4-Br-C(6)H(4) (20), 4-NO(2)-C(6)H(4) (21)] and (t-BuNH)P(mu-N-t
      Bu)(2)P(+)[(HN-t-Bu){N-(CO(2)-i-Pr)-N(H)(CO(2)-i-Pr)](4-CH(3)-C(6)H(4)SO(3)(-))
      (22) that have essentially the same structure as 2. Compound 18 has additional
      stabilization by hydrogen bonding, as revealed by X-ray structure determination.
      Finally it is shown that the in situ generated (t-BuNH)P(mu-N-t-Bu)(2)P(+)[(HN-t
      Bu){N-(CO(2)Et)-N(H)(CO(2)Et)](4-NO(2)-C(6)H(4)CO(2)(-)) can also effect
      Mitsunobu esterification. A comparison of the Ph(3)P-DIAD system with the
      analogous synthetically useful Ph(3)P-dimethyl acetylenedicarboxylate (DMAD)
      system is made.

PMID- 16438513
TI  - Synthesis and single-crystal X-ray characterization of 4,4"-functionalized 4'-(4
      bromophenyl)-2,2':6',2"-terpyridines.
AB  - To expand the utility of bis(terpyridine) metal connectivity, the selective
      symmetrical and unsymmetrical 4,4"-functionalization (-CN, -Me, -CO2Me) of 4'-(4
      bromophenyl)-2,2':6',2"-terpyridines was achieved using the Krohnke synthesis.
      The final substituted 2,2':6',2"-terpyridines along with their corresponding
      intermediates, 4a-c, were recrystallized and characterized by 1H NMR and 13C NMR
      as well as X-ray crystallography; COSY correlations were also conducted to permit
      definitive proton assignment.

PMID- 16438514
TI  - Selective synthesis of alpha-C-(alkynyl)-galactosides by an efficient tandem
      reaction.
AB  - Several alpha-C-(alkynyl)-galactosides were synthesized using a tandem reaction
      involving the addition of a metal alkynylide to a chiral acyclic epoxyaldehyde,
      followed by an in situ closure of the generated alkoxide on the epoxide function.

PMID- 16438515
TI  - Unsubstituted bicyclo[1.1.0]but-2-ylcarbinyl cations.
AB  - A synthesis for the unsubstituted bicyclo[1.1.0]but-2-ylmethanols (endo- and exo
      9) from 1,3-butadiene has been developed. Solvolyses of their sulfonates 10 and
      11 took entirely different courses, as the endo compound 10 gave rise exclusively
      to rearranged products such as cyclopent-3-en-1-ol (14), while the exo compound
      11 underwent only the substitution of the tosylate group with complete retention
      of the exo-bicyclo[1.1.0]but-2-ylmethyl skeleton. Under solvolytic conditions, 10
      reacted at very similar rates to the corresponding monocyclic substrate, that is,
      cyclopropylcarbinyl mesylate (19); in contrast, 11 reacted only three times as
      fast as n-butyl tosylate and about 1000-fold slower than 10. The nature of the
      bicyclo[1.1.0]but-2-ylcarbinyl cations has been probed by quantum chemical
      calculations. Whereas, the exo isomer (exo-18) corresponds to a local energy
      minimum, the endo isomer is only a transition state [endo-18(TS)] for an
      automerization of the nonclassical cyclopent-3-en-1-yl cation (13) and converts
      into 13 by a Wagner-Meerwein rearrangement. The most favorable isomerization of
      exo-18 also leads to 13 but via a transition state resembling the 2
      vinylcycloprop-1-yl cation [25(TS)]. On the introduction of methyl groups at
      positions 1 and 3 of exo-18, the cation is no longer an energy minimum and it
      becomes a transition state [27(TS)] for an automerization of the nonclassical 1,3
      dimethylcyclopent-3-en-1-yl cation (28). The large effect of the methyl
      substitution rationalizes the puzzling results of the previous product and rate
      studies, which utilized various substituted derivatives of bicyclo[1.1.0]but-2
      ylcarbinyl sulfonates as substrates.

PMID- 16438516
TI  - Effect of water on the functionalization of substituted anisoles with iodine in
      the presence of F-TEDA-BF4 or hydrogen peroxide.
AB  - Water was found to be a convenient reaction medium for functionalization of
      substituted anisoles using iodine in the presence of Selectfluor F-TEDA-BF(4) or
      hydrogen peroxide as mediators and oxidizers. Two types of functionalization were
      observed: iodination or oxidation. In the iodination process, two reaction routes
      were established. In the case of the first route, a high iodine atom economy was
      achieved for selective and effective iodo functionalization with a stoichiometric
      ratio of substrate/iodine/(mediator/oxidizer) = 2:1:1.2. An electrophilic
      iodination reaction process was suggested for this route, with the oxidizer
      converting the liberated iodide anion to iodine. For the second reaction route, a
      stoichiometric ratio of substrate/iodine/(mediator/oxidizer) = 1:1:1 and a lower
      iodine atom economy were observed; in this case, ion radical formation in the
      first step of the reaction was suggested. Iodine was found to be an effective
      catalyst for the oxidation of a hydroxy benzyl functional group to benzaldehyde
      using F-TEDA-BF(4). Water is an effective medium for functionalization of
      anisole, p-methoxy benzyl alcohol, 1-(4-methoxyphenyl)ethanone, o-dimethoxy
      benzene, m-dimethoxy benzene, and p-dimethoxy benzene, whereas F-TEDA-BF(4) as a
      mediator/oxidizer could be replaced by hydrogen peroxide in the case of the
      functionalization of 1-(4-methoxyphenyl)ethanone, o-dimethoxy benzene, m
      dimethoxy benzene, and p-dimethoxy benzene. Water changes the type of
      transformation of p-methoxy benzyl alcohol.

PMID- 16438517
TI  - Synthesis and antioxidant profile of all-rac-alpha-selenotocopherol.
AB  - all-rac-alpha-Selenotocopherol (6c) has been synthesized in 11 steps in 6.6%
      total yield. Key steps include chloromethylation to approach the persubstituted
      aromatic 9b and cyclization of alcohol precursor 10 by radical homolytic
      substitution at selenium to form the selenotocopherol heterocycle. Determination
      of the OH bond dissociation enthalpy (BDE) of 6c by electron paramagnetic
      resonance (EPR) equilibration techniques gave a value of 78.1 +/- 0.3 kcal mol(
      1), approximately 1 kcal mol(-1) higher than that of alpha-tocopherol. Kinetic
      studies performed by measuring oxygen uptake of the induced oxidation of styrene
      in the presence of an antioxidant showed that selenotocopherol (6c) was a
      slightly poorer inhibitor than alpha-tocopherol, in agreement with the BDE
      values. In contrast to simpler selenotocopherol analogues, 6c was not regenerable
      in the presence of a stoichiometric coreductant in a two-phase lipid peroxidation
      model.

PMID- 16438518
TI  - Oxidation of alcohols to carbonyl compounds with CrO3.SiO2 in supercritical
      carbon dioxide.
AB  - Supercritical carbon dioxide (scCO2) is an effective reaction medium to perform
      the oxidation of primary and secondary aliphatic alcohols to the corresponding
      carbonyl compounds with chromium trioxide supported on silica. These reactions
      were performed by flowing a solution of the alcohol in scCO2 through a column
      containing the supported reagent and recovering the product by depressurization.
      This method avoids the use of organic solvents and the contamination of the
      products with chromium species.

PMID- 16438519
TI  - Study of the factors that control the ratio of the products between 5
      fluorouracil, uracil, and tetrahydrobenzoxazepine O,O-acetals bearing electron
      withdrawing groups on the nitrogen atom.
AB  - (RS)-1-(2-Nitrobenzenesulfonyl)- and (RS)-1-(4-nitrobenzenesulfonyl)-3-methoxy
      1,2,3,5-tetrahydro-4,1-benzoxazepines are better substrates than 1-acyl-3-methoxy
      1,2,3,5-tetrahydro-4,1-benzoxazepine derivatives for the Lewis acid mediated
      condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile,
      stannic chloride, 50 degrees C, and a reaction time higher than 48 h are the
      optimum conditions for such condensation reactions. Under these conditions, 5
      fluorouracil preferably links to the aminalic carbon through its N-1" position,
      while the attachment of the uracil fragment is through N-3" or N-1" of the cyclic
      or acyclic products, respectively. The causes that influence the course of the
      reactions are analyzed and discussed. Examination of the (1)H NMR spectra
      revealed the presence of a single form for the secondary amine 11 and of two
      conformers for the tertiary sulfonamides 7a,b, 9a,b, and 10b and for the amides
      7d and 13, with the following distribution: 7a, 59/41; 7b, 53/47; 9a, 52/48; 9b,
      59/41; 10b, 56/44; 7d, 50/50; 13, 80/20. On increasing the temperature, the (1)H
      NMR spectrum (DMSO-d(6)) of 7b showed coalescence at 110 degrees C. The torsional
      barrier determined [DeltaG(c)++ value of 19.0 +/- 0.2 kcal.mol(-1) (79.1 +/- 1.0
      kJ.mol(-1))] proved to be the highest ever observed for sulfonamide moieties.

PMID- 16438520
TI  - Volume-demanding cis-trans isomerization of 1,2-diaryl olefins in the solid
      state.
AB  - Volume-demanding cis-trans photoisomerization of the aromatic substituted alkenes
      1-3 in the solid state at room temperature and at 50 degrees C is presented.
      Alkene 3 did not undergo the cis-trans isomerization in the solid state either at
      room temperature or at 50 degrees C. The importance of the presence of void space
      near the reaction center to facilitate the large volume change during cis-trans
      photoisomerization is discussed.

PMID- 16438521
TI  - Synthesis of oligonucleotides with 3'-terminal 5-(3-acylamidopropargyl)-3'-amino
      2',3'-dideoxyuridine residues and their reactivity in single-nucleotide steps of
      chemical replication.
AB  - Oligonucleotides with a 3'-terminal 5-alkynyl-3'-amino-2',3'-dideoxyuridine
      residue were prepared, starting from 2'-deoxyuridine. The optimized route employs
      a 2',3'-dideoxy-3'-trifluoroacetamido-5-iodouridine 5'-phosphoramidite as
      building block for DNA synthesis and involves on-support Sonogashira coupling
      with N-tritylpropargylamine to generate oligonucleotides. The amino group of the
      propargylamine side chain was acylated to accelerate primer extension reactions
      involving the 3'-amino group. Three acyl groups were identified that decrease the
      half-life for DNA-templated extension steps with 7-azabenzotriazole esters of 2'
      deoxynucleotides. The residue of 4-pyrenylbutyric acid was found to accelerate
      primer extension reactions and to render them more selective than those of the
      control primer. With this substituent, primer extension is also faster than
      previously measured for three-strand systems involving template, aminoprimer, and
      a downstream-binding helper oligonucleotide. Fast-reacting primers might become
      useful for genotyping single nucleotides.

PMID- 16438522
TI  - Stereoselectivity of intramolecular SN' cyclizations of alkyllithium reagents on
      methoxy alkenes.
AB  - The cyclization of alkyllithium reagents onto methoxy alkenes has been
      investigated. The alkyllithium reagent was generated by reductive lithiation of
      an alkyl nitrile. In an unbiased substrate, a methoxy leaving group attached to a
      stereogenic secondary carbon atom led to the cyclization product with high
      optical purity. The configuration of the product demonstrated that the
      cyclization had proceeded with high syn-S(N)' selectivity. Previously we have
      shown that 2-lithiotetrahydropyran reagents cyclize to form spirocycles with the
      alkene cis to the pyran oxygen. Substrates were prepared to evaluate the
      importance of the configuration of the secondary allyl methyl ether against the
      alpha-alkoxy alkyllithium configuration. In the matched case (cyano acetal 38), a
      very selective cyclization ensued. In the mismatched case (cyano acetal 39), the
      spiro ether selectivity dominated. The syn-S(N)' selectivity overcame the normal
      E selectivity in the cyclization and accounted for the major product, Z-alkene
      45. Thus the stereochemical preference in these alkyllithium cyclizations is
      dominated by the spiroether effect, followed by the syn-S(N)' selectivity and
      finally the preference for E-alkene formation.

PMID- 16438523
TI  - An unusual reaction of the natural compound benaphthamycin B: theoretical study
      of a model system.
AB  - The surprising and complex transformation of benaphthamycin B to give quinone 2a
      is investigated theoretically with a model compound, 1,5-dihydroxy-4-methoxy-2,3
      dimethylanthraquinone (3). The detailed study is performed using both DFT and
      perturbation theory under inclusion of solvent effects. Several individual steps
      (reduction and hydrolysis, water elimination, ether cleavage, and oxidation) of
      the proposed reaction cascade calculated at the PCM-MP2/6-31G(d)//B3LYP/6-31G(d)
      level of theory are presented and discussed. It is shown that the key step, the
      ether cleavage as an S(N)2 reaction leading to the anthrone 12a, possesses a
      smaller activation barrier compared to the alternative process yielding 12b.
      Therefore, the formation of the thermodynamically preferred model quinone 13a is
      also the kinetically favored pathway: The results of the calculated model
      reaction should also be valid for benaphthamycin B (1).

PMID- 16438524
TI  - A convenient preparation of heteroaryl sulfonamides and sulfonyl fluorides from
      heteroaryl thiols.
AB  - Heteroaromatic thiols may be oxidized to the sulfonyl chloride at low temperature
      (-25 degrees C) by using 3.3 equiv of aqueous sodium hypochlorite. The reaction
      is rapid, avoids the use of chlorine gas, and succeeds with substrates that have
      previously been found to afford little or none of the sulfonamide product with
      other procedures. The method allows the preparation of the sulfonyl fluorides,
      which are stable enough to be purified and stored, making them potentially useful
      monomers in parallel chemistry efforts.

PMID- 16438525
TI  - Total synthesis and revision of C6 stereochemistry of (+)-amphidinolide W.
AB  - An enantioselective first total synthesis and structural revision of the
      cytotoxic natural product amphidinolide W is described. We initially investigated
      a ring-closing metathesis based synthetic strategy to form the 12-membered
      macrocycle. This strategy was unsuccessful as it led to formation of a 17
      membered macrocycle. Subsequently, we explored an alternative strategy that
      involved cross-metathesis followed by a Yamaguchi macrolactonization reaction
      sequence utilizing the same key intermediates. This strategy led to the synthesis
      of amphidinolide W. The synthesis was carried out in a convergent manner, and
      four of the five stereogenic centers in amphidinolide W were set by asymmetric
      synthesis. The synthesis features Sharpless asymmetric dihydroxylation,
      diastereoselective alkylation, efficient cross-metathesis of functionalized
      substrates, and novel functional group transformations using selective lipase
      catalyzed hydrolysis of the primary acetate group. Of particular note, the C6
      absolute stereochemistry of amphidinolide W has now been revised through our
      synthesis.

PMID- 16438526
TI  - Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a
      double annulation strategy from alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)
      acetals.
AB  - A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3
      d]pyrimidines via a double [5 + 1] annulation strategy starting from easily
      available alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals 1 and cheap
      reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the
      double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were
      created in high to excellent yields by a formal [5C + 1N] annulation reaction of
      ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step
      of the double annulation strategy, the highly functionalized dihydropyrido[2,3
      d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1
      = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were
      constructed, respectively, in fair to good yields by reacting 2 with excessive
      Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1]
      annulation step, including a formal [5 + 1] annulation and accompanied
      chlorovinylation, chloroformylation, amination, and aromatization reactions, is
      proposed.

PMID- 16438527
TI  - Anti versus syn opening of epoxides derived from 9-(3-deoxy-beta-D-glycero-pent-3
      enofuranosyl)adenine with Me3Al: factors controlling the stereoselectivity.
AB  - Upon epoxidation with dimethyldioxirane, the 2',5'-bis-O-silyl derivatives of 9
      (3-deoxy-beta-D-glycero-pent-3-enofuranosyl)adenine gave the respective "3',4'
      up" epoxides exclusively. Reaction between these epoxides and Me3Al was
      investigated in detail. It was found that the stereoselectivity of epoxide ring
      opening (anti versus syn) varied significantly upon changing the amount of Me3Al,
      the solvent, the O-silyl protecting group, and the reaction temperature. A
      possible reaction mechanism is proposed.

PMID- 16438528
TI  - Iron-phosphine, -phosphite, -arsine, and -carbene catalysts for the coupling of
      primary and secondary alkyl halides with aryl Grignard reagents.
AB  - Simple catalysts formed in situ from iron chloride and a wide range of
      monodentate and bidentate phosphines and arsines have been screened in the
      coupling of alkyl halides bearing beta-hydrogens with aryl Grignard reagents. The
      best of these show excellent activity, as do catalysts formed in situ with
      monodentate trialkyl and triaryl phosphite ligands. N-heterocyclic carbene-based
      precatalysts, either preformed or made in situ, also show excellent performance.

PMID- 16438529
TI  - Synthesis of sulfonium sulfate analogues of disaccharides and their conversion to
      chain-extended homologues of salacinol: new glycosidase inhibitors.
AB  - Four chain extended homologues of salacinol, a naturally occurring glycosidase
      inhibitor, were prepared for evaluation as inhibitors of glucosidase enzymes
      involved in the breakdown of carbohydrates. The syntheses involved the reactions
      of 1,4-anhydro-2,3,5-tri-O-benzyl-4-thio-D-arabinitol with cyclic sulfate
      derivatives of different monosaccharides. Debenzylation of the products afforded
      the novel sulfonium sulfate derivatives of D-glucose, D-galactose, D-arabinose,
      and D-xylose that are of interest in their own right as glycosidase inhibitors.
      Reduction to the corresponding alditols then afforded the homologues of salacinol
      containing polyhydroxylated, acyclic chains of 5- and 6-carbons, differing in
      stereochemistry at the stereogenic centers. Three of the chain-extended
      homologues inhibited recombinant human maltase glucoamylase, one of the key
      intestinal enzymes involved in the breakdown of glucose oligosaccharides in the
      small intestine, with Ki values in the low micromolar range, of approximately the
      same magnitude as salacinol, thus providing lead candidates for the treatment of
      Type 2 diabetes.

PMID- 16438530
TI  - Role of barium(II) in the determination of the absolute configuration of chiral
      amines by 1H NMR spectroscopy.
AB  - The assignment of the absolute configuration of alpha-chiral primary amines by
      complexation of their MPA derivatives with Ba2+ and NMR analysis of the changes
      generated is presented. All that is required is (a) the derivatization of the
      amine of unknown configuration with one enantiomer of the auxiliary reagent
      (MPA), either (R) or (S)-alpha-methoxyphenylacetic acid, (b) the recording of the
      1H NMR spectrum of the resulting amide in MeCN-d3, (c) the addition of Ba(ClO4)2
      to the NMR tube, and (d) the recording of a second spectrum after a few minutes
      of shaking. The above steps take a few minutes and are followed by an analysis of
      the shifts (measured as Deltadelta(Ba)) produced on the L1 and L2 substituents of
      the amine by the addition of Ba2+ and their comparison with those expected from
      the conformational changes produced by the complexation. The conformational
      changes initiated by complexation have been subjected to NMR and CD studies,
      which showed that the formation of the complex shifts the equilibrium from an
      antiperiplanar (AP) to a synperiplanar (SP) form, leading to an increase of the
      shielding by the phenyl group of MPA of the substituent of the amine located on
      the same side. In addition, theoretical calculations [density functional theory
      (DFT)] provide further support for the formation, structure, and stability of the
      complexes. The general applicability of this method and the trustworthiness of
      the resulting configurational assignment were guaranteed with a series of amines
      of known absolute configuration and varied structures, used as test compounds.
      The method proposed is simple, fast, and inexpensive, and it requires a very
      small amount of sample, only one derivatization, and the recording of just two 1H
      NMR spectra at room temperature. A graphical guide to simplify the application of
      this method is included.

PMID- 16438531
TI  - Phenanthroline dicarboxamide-based helical foldamers: stable helical structures
      in methanol.
AB  - A series of new aromatic oligoamides 2-5 based on 1,10-phenanthroline diacid and
      o-phenylenediamine have been synthesized through a convergent segment coupling
      strategy. These oligomers can fold into well-defined helical structures in
      solution through intramolecular hydrogen bonds and aromatic stacking
      interactions, which has been established by 1H NMR, fluorescence, and UV/vis
      spectra. In particular, it was found that the oligomers were more favorable to
      fold into stable helical structures in methanol than in chloroform and
      dichloromethane. The helical foldamers formed in the solid state have been
      characterized by single-crystal X-ray diffraction analysis. The results showed
      that the high curvature of the strands led to one and a half turns for both 2 and
      21, three turns for 4, and nearly four turns for 5.

PMID- 16438533
TI  - Palladium-catalyzed dimerization of conjugated diynes: synthesis of (E)-1,2
      divinyldiethynylethenes having donor and acceptor chromophores at the terminus of
      alkyne.
AB  - (E)-1,2-Divinyldiethynylethenes (DVDEEs) having donor and acceptor chromophores
      at the terminals of alkyne unit 7' were synthesized by the palladium/HOAc
      catalyzed dimerization of the conjugated diynes 8 bearing an Si group at the
      terminus of alkyne (R(1) position), followed by desilylation and subsequent
      Sonogashira reaction of the resulting terminal alkyne 10 with aryl iodides.

PMID- 16438532
TI  - Synthesis and structure of hydroxyl acids of general structure 7,7
      alkenyl/alkynyl-5-hydroxymethyl-6-oxabicyclo[3.2.1]octane-1-carboxylic acid.
AB  - The open-ended hollow tubular structure formed by inclusion of water molecules in
      the packing of the hydroxyl acid 1 (R1 = CH2OH, R2 = ethyl groups) led to the
      synthesis and structural study of their unsaturated analogues. In this article we
      report on a general and practical large-scale synthesis of hydroxyl acids that
      possess alkenyl and alkynyl appendages. Substitution of the ethyl groups in 1
      with unsaturated two-carbon appendages has a different effect on the molecular
      structure and on the hydrogen-bonding pattern. No variation has been induced by
      substitution of only one ethyl group with a vinyl one, although the substitution
      of both ethyl groups with vinyl or acetylene appendages has the greatest effect
      on the molecular structure and results in different hydrogen-bonding motifs.

PMID- 16438534
TI  - Porphyrin dyads bearing carbon tethers for studies of high-density molecular
      charge storage on silicon surfaces.
AB  - Redox-active molecules that afford high charge density upon attachment to an
      electroactive surface are of interest for use in molecular-based information
      storage applications. One strategy for increasing charge density is to covalently
      link a second redox center to the first in an architecture that uses the vertical
      dimension in essentially the same molecular footprint. Toward this end, a set of
      four new porphyrin dyads have been prepared and characterized. Each dyad consists
      of two zinc porphyrins, an intervening linker (p-phenylene or 4,4'
      diphenylethyne), and a surface attachment group (ethynyl or triallyl group). The
      porphyrin dyads were attached to an electroactive Si(100) surface and
      interrogated via electrochemical and FTIR techniques. The charge density
      obtainable for the ethynyl-functionalized porphyrin dyads is approximately double
      that observed for an analogously functionalized monomer, whereas that for the
      triallyl-functionalized dyads is at most 40% larger. These results indicate that
      the molecular footprint of the former dyads is similar to that of a monomer while
      that of the latter dyads is larger. For both the ethynyl- and triallyl
      functionalized porphyrin dyads, higher charge densities (smaller molecular
      footprints) are obtained for the molecules containing the 4,4'-diphenylethyne
      versus the p-phenylene linker. This feature is attributed to the enhanced
      torsional flexibility of the former linker compared with that of the latter,
      which affords better packed monolayers. The FTIR studies indicate that the
      adsorption geometry of all the dyads is qualitatively similar and similar to that
      of monomers. However, the dyads containing the 4,4'-diphenylethyne linker sit
      somewhat more upright on the surface than those containing the p-phenylene
      linker, generally consistent with the smaller molecular footprint for the former
      dyads. Collectively, the high surface charge density (34-58 muC.cm(-)(2)) of the
      porphyrin dyads makes these constructs viable candidates for molecular
      information-storage applications.

PMID- 16438535
TI  - A general route toward the synthesis of the cladiellin skeleton utilizing a SmI2
      mediated cyclization.
AB  - An efficient synthesis of the cladiellin skeleton is reported utilizing methods
      that were previously developed in this laboratory. The approach is based on a
      SmI(2)-mediated cyclization reaction for the construction of the oxacyclononane
      unit. A [4 + 3] annulation strategy was used to create the octahydroisobenzofuran
      moiety. This route provides the cladiellin skeleton in only 14 steps without the
      use of protecting groups. The present approach also enabled the synthesis of the
      3,7-diastereomer of the natural product polyanthellin A.

PMID- 16438536
TI  - Molecular-recognition properties of a water-soluble cucurbit[6]uril analogue.
AB  - The molecular-recognition properties of the cucurbit[6]uril analogue (1) in
      aqueous buffer (sodium acetate, 50 mM, pH 4.74, 25 degrees C) toward a variety of
      guests including alkanediamines (6-12), aromatics (14-32), amino acids (33-36),
      and nucleobases (37-42) were studied by fluorescence spectroscopy. For the
      alkanediamines studied (H2N(CH)nNH2, n = 6, 7, 8, 9, 10, 11, 12), the association
      constants increase as the length of the alkane (n) is increased. Host 1 is
      capable of forming strong complexes with guests containing aromatic rings with
      association constants (Ka) ranging from 10(2) to 10(6) M(-1) as a result of the
      favorable pi-pi interactions that occur between host 1 and the aromatic rings of
      the guest when bound in the cavity of 1. Biologically relevant guests such as
      amino acids and nucleobases are also bound in the cavity of 1 with Ka values
      ranging from 10(3) to 10(6) M(-1). Consequently, cucurbit[6]uril analogue 1
      functions as a versatile fluorescent sensor for the presence of a wide range of
      chemically and biologically important substances in aqueous solution including
      nitroaromatics, neurotransmitters, amino acids, and nucleobases.

PMID- 16438537
TI  - 3He NMR as a sensitive probe of fullerene reactivity: [2 + 2] photocycloaddition
      of 3-methyl-2-cyclohexenone to C70.
AB  - The [2 + 2] photoadditions of 3-methyl-2-cyclohexenone to C70 and 3He@C70 have
      been studied by a combination of HPLC chromatography and FAB-MS, as well as IR
      and 1H and 3He NMR spectroscopies. The total yield of the mixture of monoadducts
      was 55% (67% on the basis of the recovered C70). The use of 3He NMR was
      especially powerful in determining the regioselectivity of the photoaddition
      reaction of enone to C70. Results of the 3He NMR experiments conducted on the
      product mixture implicate the two [6,6] bonds closest to the poles of the
      fullerene (C1-C2 and C5-C6) in the photoaddition process. This reaction mode is
      analogous to that of most thermal addition reactions to C70. Separation and
      characterization of the product mixture shows that eight distinct monoadducts are
      formed in the photoaddition, namely, the four diastereomeric adducts to the C1-C2
      and C5-C6 bonds of the C70 cage, each consisting of cis- and trans-fused isomers
      in a ratio of 2:3. The major mode of photoaddition, accounting for 65% of the
      product mixture, involves addition to the C1-C2 bond of the ovoid fullerene.
      Mechanistic implications of these findings are discussed.

PMID- 16438538
TI  - Helix formation in alpha,gamma- and beta,gamma-hybrid peptides: theoretical
      insights into mimicry of alpha- and beta-peptides.
AB  - Alpha,gamma- and beta,gamma-hybrid peptides, which are composed of two different
      homologous amino acid constituents in alternate order, are suggested as novel
      classes of peptide foldamers. On the basis of a systematic conformational search
      employing the methods of ab initio MO theory, the possibilities for the formation
      of periodic secondary structures in these systems are described. The
      conformational analysis provides a great number of helix conformers widely
      differing in energy, which can be arranged into three groups: (i) helices with
      all hydrogen bonds formed in forward direction along the sequence, (ii) helices
      with all hydrogen bonds in backward direction, and (iii) helices with alternate
      hydrogen-bond directions (mixed or beta-helices). Most stable are representatives
      of beta-helices, but their stability decreases considerably in more polar
      environments in comparison to helix conformers from the other two classes. There
      is a great similarity between the overall topology of the most stable hybrid
      peptide helices and typical helices of peptides which are exclusively composed of
      a single type of homologous amino acids. Thus, the helices of the beta,gamma
      hybrid peptides mimic perfectly those of the native alpha-peptides as, for
      instance, the well-known alpha-helix, whereas the most stable helix conformers of
      alpha,gamma-hybrid peptides correspond well to the overall structure of beta
      peptide helices. The two suggested novel hybrid peptide classes expand
      considerably the pool of peptide foldamers and may be promising tools in peptide
      design and in material sciences.

PMID- 16438539
TI  - An alternative interpretation of the C-H bond strengths of alkanes.
AB  - A new model based on 1,3 repulsive steric interactions (geminal repulsion) is
      proposed for explaining the variation in the C-H bond strengths of the alkanes.
      The model builds from the assumption that 1,3 repulsive interactions are the
      major factor in determining the stability of a C-C or C-H bond in an alkane. From
      this simple premise, the model successfully reproduces the effect of branching on
      the stability of alkanes, alkyl radicals, and alkenes. The results suggest that
      geminal repulsion can provide a simple, unified explanation for these fundamental
      stability trends. Although previous explanations have been widely accepted, it is
      shown that the theoretical support for them is relatively shallow and that the
      current hyperconjugative stabilization model is inconsistent with several
      experimental and computational results concerning alkyl radicals. In contrast, an
      explanation based on geminal repulsion provides a general conceptual framework
      for rationalizing each of these stability trends and is based on a physical
      effect that is known to play a role in the stability of alkanes and related
      species.

PMID- 16438540
TI  - Catalytic asymmetric total synthesis of (+)-lactacystin.
AB  - Total synthesis of (+)-lactacystin, a potent and selective proteasome inhibitor,
      was accomplished using a catalytic enantioselective Strecker reaction of a
      ketoimine as the initial key step. An enone-derived N-phosphinoyl ketoimine 7 was
      selected as a stable masked alpha-hydroxy ketoimine analogue. Excellent
      enantioselectivity (98% ee) and practical catalyst activity were produced under
      the optimized catalyst preparation method using 2.5 mol % Gd{N(SiMe3)2}3 as a
      metal source and 3.8 mol % D-glucose-derived ligand 8. This reaction was
      conducted on a 5 g scale. The chiral tetrasubstituted C-5 carbon efficiently
      controlled the stereochemistry of the other three chiral centers of lactacystin.
      Chelation-controlled Meerwein-type reduction of ketone 5 using i-PrMgBr
      (originally reported by Kang in a related substrate) selectively produced the
      desired secondary alcohol at the C-9 position. The C-6 hydroxy and C-7 methyl
      groups were introduced via a silyl conjugate addition followed by the Tamao
      oxidation and Donohoe methylation, respectively, in a highly stereoselective
      manner. A practical amount of enantiomerically pure clasto-lactacystin beta
      lactone (2), the biologically active form of (+)-lactacystin, can be synthesized
      using this route. clasto-Lactacystin beta-lactone (2) was converted to (+)
      lactacystin following the reported procedure.

PMID- 16438541
TI  - A concise synthesis of tetrahydroxy-LCB, alpha-galactosyl ceramide, and 1,4
      dideoxy-1,4-imino-L-ribitol via D-allosamines as key building blocks.
AB  - The total syntheses of tetrahydroxy-LCB 1, alpha-galactosyl ceramide 2, and 1,4
      dideoxy-1,4-imino-L-ribitol 3 via D-allosamine derivatives as common synthons are
      described here.

PMID- 16438542
TI  - Solid-phase synthesis with resin-bound triarylbismuthanes: traceless and
      multidirectional cleavage of unsymmetrical biphenyls.
AB  - A multistep solid-phase organic synthesis with resin-bound bismuth linker is
      described. The flexibilities inherent in this system through novel chemoselective
      cross-coupling reactions, in conjunction with multidirectional and/or traceless
      cleavage methodologies, are exploited.

PMID- 16438544
TI  - Cucurbit[7]uril mediates the stereoselective [4+4] photodimerization of 2
      aminopyridine hydrochloride in aqueous solution.
AB  - The 2:1 guest-host complex of 2-aminopyridine hydrochloride with cucurbit[7]uril
      (CB[7]) undergoes a stereoselective [4+4] photodimerization reaction in aqueous
      solution to yield exclusively the anti-trans isomer of 4,8-diamino-3,7
      diazatricyclo[4.2.2.2(2,5)]dodeca-3,7,9,11-tetraene, and in the absence of CB[7],
      the photochemical reaction produces the anti-trans and syn-trans photodimers in a
      4:1 ratio. In addition, encapsulation of the photodimer product in the CB[7]
      cavity stabilizes it with respect to the otherwise observed rearomatization to
      the 2-aminopyridine monomer at room temperature.

PMID- 16438543
TI  - Synthesis of oxacalixarene-locked bisporphyrins and higher oligomers.
AB  - The efficient one-step synthesis of oxacalixarene-bisporphyrins and higher
      oligomers from readily available starting materials is described. The X-ray
      structure of one oxacalix[4]arene-locked cofacial bisporphyrin, prepared in 91%
      yield, shows an 1,3-alternate conformation of the molecule with partial overlap
      of the two porphyrin rings. 1H NMR data supports a similar conformation in
      solution. The absorption and emission spectra of oxacalixarene-porphyrins are
      briefly discussed.

PMID- 16438545
TI  - Hinged molecular capsules: synthesis and conformational control via temperature,
      pH, or solvent composition.
AB  - Three new covalently linked molecular capsules were synthesized from their
      resorcinarene cavitand precursors in good yields. The capsules undergo reversible
      conformational switching between the closed "vase" form and the open "kite" form
      upon temperature or pH variation. The kite conformation obtained via either
      method in CDCl(3) switches to vase conformation upon addition of polar solvents
      such as acetone-d(6) or THF-d(8).

PMID- 16438546
TI  - Encapsulation of quinine by beta-cyclodextrin: excellent model for mimicking
      enzyme-substrate interactions.
AB  - An inclusion complex formed by beta-cyclodextrin and quinine has been
      investigated in solution and in the solid state, in which the quinoline ring and
      the aliphatic ring locate in different hydrophobic cavities, respectively. The
      study on the inclusion geometry and weak interactions shows that the difference
      in conformation for this complex is a result of three main packing arrangement
      considerations, which can provide an ideal model mimicking enzyme-substrate
      interactions.

PMID- 16438547
TI  - Natural bond orbital analyses of persulfoxide stabilization by remote functional
      groups. The conformationally induced electrostatic stabilization sulfide
      photooxygenation mechanism.
AB  - The conformationally induced electrostatic stabilization (CIES) sulfide
      photooxygenation mechanism was computationally examined using an ab initio model
      and extended to the study of new donor atoms. The MP2/6-31G(d) geometries and a
      natural population analysis of natural lone-pair orbitals on the donor atoms
      support the mechanism and reveal that oxygen and nitrogen donor groups are more
      stabilizing than sulfur.

PMID- 16438548
TI  - Stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine
      (jaspine B) from D-xylose.
AB  - The first naturally occurring anhydrophytosphingosine, pachastrissamine (jaspine
      B), a marine compound cytotoxic toward P388, A549, HT29, and MEL28 cell lines at
      IC(50) = 0.01 microg/mL level, has been stereoselectively synthesized from D
      xylose in 10 linear steps with 25.7% overall yield.

PMID- 16438549
TI  - Palladium-catalyzed arylation and heteroarylation of azolopyrimidines.
AB  - A comparative study of the palladium-catalyzed arylation and heteroarylation of 5
      bromoazolopyrimidines shows that aryl and electron-rich heteroaryl boronic acids
      gave higher yields than those obtained using the corresponding aryl and
      heteroaryl tributyl stannanes. In contrast, the reaction with electron-poor
      heteroaryl tributyl stannanes gave better results than the corresponding boronic
      acids.

PMID- 16438550
TI  - Cu-catalyzed N-arylation of oxazolidinones: an efficient synthesis of the kappa
      opioid receptor Agonist CJ-15161.
AB  - An efficient method for intermolecular N-arylation of oxazolidinones using
      catalytic copper in the presence of a bidentate ligand is reported. The
      conditions allow the use of copper and can be used to prepare enantiopure N-aryl
      beta-amino alcohols. A short, scalable synthesis of CJ-15,161 is also reported.
      The required amines were obtained from the precursor alpha-amino acids or, more
      conveniently, from the corresponding 1,2-amino alcohols.

PMID- 16438551
TI  - Synthesis of a sulfonium ion analogue of the glycosidase inhibitor swainsonine.
AB  - The synthesis of a bicyclic sulfonium ion analogue of a naturally occurring
      indolizidine alkaloid, swainsonine, in which the bridgehead nitrogen atom is
      replaced by a sulfonium ion, has been achieved by a multistep synthesis starting
      from (2S,3S,4R)-2,3-dibenzyloxy-4-formaldehyde-thiolane. The synthetic strategy
      relies on the intramolecular displacement of a leaving group on a pendant acyclic
      chain by a cyclic thioether. This bicyclic sulfonium salt provides a candidate
      with which to further probe the hypothesis that a sulfonium salt carrying a
      permanent positive charge would be an effective glycosidase inhibitor.

PMID- 16438552
TI  - Stereoselective synthesis of 3-aminoindan-1-ones and subsequent incorporation
      into HIV-1 protease inhibitors.
AB  - A new method for the stereoselective synthesis of 3-aminoindan-1-ones from
      triflates of salicylic sulfinyl imines and ethylene glycol vinyl ether has been
      developed. The reaction sequence starts with a regioselective Heck reaction
      followed by stereoselective Lewis acid mediated annulation. Acidic cleavage of
      the sulfinamides produced pure (R)- and (S)-3-aminoindan-1-ones, which were
      successfully isolated and incorporated into active HIV-1 protease inhibitors.

PMID- 16438553
TI  - Synthesis of the putative structure of fistulosin using the ruthenium-catalyzed
      cycloisomerization of diene.
AB  - Fistulosin 1, which was isolated from the root of the Welsh onion, is a novel
      indole alkaloid that has antifungal activity. The first total synthesis of the
      reported structure of fistulosin using our cycloisomerization of diene is
      described.

PMID- 16438554
TI  - Activation of TMSCN by N-heterocyclic carbenes for facile cyanosilylation of
      carbonyl compounds.
AB  - N-Heterocyclic carbenes were found to be highly effective organocatalysts in
      activating TMSCN for facile cyanosilylation of carbonyl compounds. Cyano transfer
      from TMSCN to aldehydes and ketones proceeds at room temperature in the presence
      of only 0.01-0.5 mol % of N-heterocyclic carbene (1), leading to a range of
      trimethylsilylated cyanohydrins in very good to excellent yields. These
      conditions are extremely mild and simple and tolerate various functional groups.

PMID- 16438555
TI  - Short and practical synthesis of O-(p-biphenoyl)-N-tosyl-allo-threonine-derived
      oxazaborolidinone catalyst.
AB  - O-(p-Biphenoyl)-N-tosyl-(L)-allo-threonine methyl ester is synthesized in three
      steps (65% overall yield) starting from commercially available (L)-allo-threonine
      methyl ester hydrochloride by N-acylation followed by N,O-acyl migration with
      inversion of the beta carbinol carbon and N-tosylation. Treatment of the methyl
      ester with dibromophenylborane gives oxazaborolidinone 1, which can be used as a
      Lewis acid catalyst for the asymmetric Michael and Diels-Alder reactions.

PMID- 16438556
TI  - Palladium-catalyzed intramolecular N-arylation of heteroarenes: a novel and
      efficient route to benzimidazo[1,2-a]quinolines.
AB  - An efficient new route for the synthesis of benzimidazo[1,2-a]quinolines has been
      developed via the palladium-catalyzed intramolecular Buchwald-Harwtig aryl
      amination of newly synthesized 2-(2'-bromoanilino)quinolines.

PMID- 16438557
TI  - Palladium-catalyzed homocoupling and cross-coupling reactions of aryl halides in
      poly(ethylene glycol).
AB  - The direct coupling of aryl halides to prepare symmetrical and unsymmetrical
      biaryls were performed successfully in poly(ethylene glycol) (PEG) using Pd(OAc)2
      as the catalyst in the absence of other additives or reductants. The selectivity
      toward biaryl depended on the amount of PEG used. Excessive PEGs induce the
      increase of hydrodehalogenation product, and the best selectivity to biaryl is
      obtained when the concentration of the hydroxyl group in PEG achieves 100 mol %
      relative to aryl halides. The catalyst system could be recycled and reused up to
      five times with no loss of catalytic activity.

PMID- 16438560
TI  - Exact quantum dynamics of N(2D) + H2 --> NH + H reaction: cross-sections, rate
      constants, and dependence on reactant rotation.
AB  - Using an exact Chebyshev wave packet method, initial state-specified
      (upsilon(i)=0, j(i)=0,2) integral cross-sections and rate constants are obtained
      for the title reaction on the latest ab initio potential energy surface. Reaction
      probabilities up to J=29 are dependent on the reactant rotation and show mild
      oscillations superimposed on a broad background. Due to a barrier in the entrance
      channel, the cross sections increase with energy with clear thresholds and the
      rate constants vary with temperature in the Arrhenius form. The calculated
      canonical rate constant is in good agreement with the experimental measurements.
      Our results also indicate that the quasiclassical trajectory method
      underestimates the rate due to the neglect of tunneling, while the quantum
      statistical approach overestimates because of the short lifetime of the reaction
      intermediate.

PMID- 16438561
TI  - Dissipative dynamics of laser induced nonadiabatic molecular alignment.
AB  - Nonadiabatic alignment induced by short, moderately intense laser pulses in
      molecules coupled to dissipative environments is studied within a nonperturbative
      density matrix theory. We focus primarily on exploring and extending a recently
      proposed approach [Phys. Rev. Lett. 95, 113001 (2005)], wherein nonadiabatic
      laser alignment is used as a coherence spectroscopy that probes the dissipative
      properties of the solvent. To that end we apply the method to several molecular
      collision systems that exhibit sufficiently varied behavior to represent a broad
      variety of chemical environments. These include molecules in low temperature gas
      jets, in room temperature gas cells, and in dense liquids. We examine also the
      possibility of prolonging the duration of the field free (post-pulse) alignment
      in dissipative media by a proper choice of the system parameters.

PMID- 16438562
TI  - On the unphysical impact of complex absorbing potentials on the Hamiltonian and
      its remedy.
AB  - The introduction of complex absorbing potentials as numerical tools to stabilize
      or increase the efficiency of calculations based on wave-packet propagation or on
      eigenvalue problems has the drawback of causing a modification of the Hamilton
      operator of the problem. In this work the consequences of such a modification are
      analyzed and the corrections required in order to properly describe the original
      physical process are derived. As an example, the decay of excited molecular
      states is considered: it is shown that the standard time-independent expression
      for the decay spectrum loses its validity when a complex absorbing potential is
      introduced in the nuclear Hamilton operator of the problem. To remedy the
      situation, a new, very stable formula is derived and tested on relevant model
      studies. Numerical examples are discussed.

PMID- 16438563
TI  - Construction of environment states in quantum-chemical density-matrix
      renormalization group calculations.
AB  - The application of the quantum-chemical density-matrix renormalization group
      (DMRG) algorithm is cumbersome for complex electronic structures with many active
      orbitals. The high computational cost is mainly due to the poor convergence of
      standard DMRG calculations. A factor which affects the convergence behavior of
      the calculations is the choice of the start-up procedure. In this start-up step
      matrix representations of operators have to be calculated in a guessed many
      electron basis of the DMRG environment block. Different possibilities for the
      construction of these basis states exist, and we first compare four procedures to
      approximate the environment states using Slater determinants explicitly. These
      start-up procedures are applied to DMRG calculations on a sophisticated test
      system: the chromium dimer. It is found that the converged energies and the rate
      of convergence depend significantly on the choice of the start-up procedure.
      However, since already the most simple start-up procedure, which uses only the
      Hartree-Fock determinant, is comparatively good, Slater determinants, in general,
      appear not to be a good choice as approximate environment basis states for
      convergence acceleration. Based on extensive test calculations it is demonstrated
      that the computational cost can be significantly reduced if the number of total
      states m is successively increased. This is done in such a way that the
      environment states are built up stepwise from system states of previous truncated
      DMRG sweeps for slowly increasing m values.

PMID- 16438564
TI  - Coherent control of pump-probe signals of helical structures by adaptive pulse
      polarizations.
AB  - The simplification of the pump-probe spectrum of excitons by pure-phase
      polarization pulse shaping is investigated by a simulation study. The state of
      light is manipulated by varying the phases of two perpendicular polarization
      components of the pump, holding its total spectral and temporal intensity
      profiles fixed. Genetic and iterative Fourier transform algorithms are used to
      search for pulse phase functions that optimize the ratio of the signal at two
      frequencies. New features are extracted from the congested pump-probe spectrum of
      a helical pentamer by selecting a combination of Liouville space pathways. Tensor
      components which dominate the optimized spectra are identified.

PMID- 16438565
TI  - Density-functional theory with effective potential expressed as a mapping of the
      external potential: applications to open-shell molecules.
AB  - In this paper we apply the direct-mapping density-functional theory (DFT) to open
      shell systems, in order to get many-electron wave functions having the same
      transformation properties as the eigenstates of the exact Hamiltonians. Such a
      case is that of spin, where in order to get the magnetic properties, the many
      particle states must be eigenstates not only of S(z) but also of S2. In this
      theory the Kohn and Sham [Phys. Rev. A 140, 1133 (1965)] potential is expressed
      directly as a mapping of the external potential. The total energies of the
      molecules calculated were satisfactory as their relative deviations (deltaEE)
      from the exact Hartree-Fock ones were of the order of 10(-4). This accuracy is
      much higher than that of the standard DFT in its local exchange potential
      approximation. This method does not need an approximate density as input, as the
      effective potential is derived directly from the external potential.

PMID- 16438566
TI  - Density fitting of two-electron integrals in extended systems with translational
      periodicity: the Coulomb problem.
AB  - Density fitting approach to Coulomb integrals for infinite systems with
      translational periodicity is reformulated in direct space. Despite of the Coulomb
      infinite decay of some integrals, direct-space calculation is shown to be
      feasible. Moreover, we show that the direct-space ansatz is completely equivalent
      to our previous formulation in reciprocal space. Computational demands scale
      linearly with the number of unit cells. In addition, direct-space treatment has
      some practical advantages over the reciprocal-space formulation. The efficiency
      of our scheme is demonstrated on systems with translational periodicity in one
      dimension. Computation time takes only a small fraction of the conventional
      calculation with exact integrals. We show that for infinite systems auxiliary
      basis sets of equally good quality as for molecules can be constructed in a
      systematic way.

PMID- 16438567
TI  - Relativistic small-core energy-consistent pseudopotentials for the alkaline-earth
      elements from Ca to Ra.
AB  - Small-core ten-valence electron energy-consistent scalar- and two-component
      relativistic pseudopotentials for the alkaline-earth elements from Ca to Ra are
      presented. The accuracy and reliability of these pseudopotentials are discussed
      in terms of their ability to reproduce all-electron calculated and experimental
      dipole polarizabilities and ionization potentials.

PMID- 16438568
TI  - Semiempirical hybrid density functional with perturbative second-order
      correlation.
AB  - A new hybrid density functional for general chemistry applications is proposed.
      It is based on a mixing of standard generalized gradient approximations (GGAs)
      for exchange by Becke (B) and for correlation by Lee, Yang, and Parr (LYP) with
      Hartree-Fock (HF) exchange and a perturbative second-order correlation part (PT2)
      that is obtained from the Kohn-Sham (GGA) orbitals and eigenvalues. This virtual
      orbital-dependent functional contains only two global parameters that describe
      the mixture of HF and GGA exchange (a(x)) and of the PT2 and GGA correlation (c),
      respectively. The parameters are obtained in a least-squares-fit procedure to the
      G297 set of heat of formations. Opposed to conventional hybrid functionals, the
      optimum a(x) is found to be quite large (53% with c=27%) which at least in part
      explains the success for many problematic molecular systems compared to
      conventional approaches. The performance of the new functional termed B2-PLYP is
      assessed by the G297 standard benchmark set, a second test suite of atoms,
      molecules, and reactions that are considered as electronically very difficult
      (including transition-metal compounds, weakly bonded complexes, and reaction
      barriers) and comparisons with other hybrid functionals of GGA and meta-GGA
      types. According to many realistic tests, B2-PLYP can be regarded as the best
      general purpose density functional for molecules (e.g., a mean absolute deviation
      for the two test sets of only 1.8 and 3.2 kcal/mol compared to about 3 and 5
      kcal/mol, respectively, for the best other density functionals). Very
      importantly, also the maximum and minimum errors (outliers) are strongly reduced
      (by about 10-20 kcal/mol). Furthermore, very good results are obtained for
      transition state barriers but unlike previous attempts at such a good
      description, this definitely comes not at the expense of equilibrium properties.
      Preliminary calculations of the equilibrium bond lengths and harmonic vibrational
      frequencies for diatomic molecules and transition-metal complexes also show very
      promising results. The uniformity with which B2-PLYP improves for a wide range of
      chemical systems emphasizes the need of (virtual) orbital-dependent terms that
      describe nonlocal electron correlation in accurate exchange-correlation
      functionals. From a practical point of view, the new functional seems to be very
      robust and it is thus suggested as an efficient quantum chemical method of
      general purpose.

PMID- 16438569
TI  - A reversible minimum-to-minimum mapping method for the calculation of free-energy
      differences.
AB  - A general method is introduced for the calculation of the free-energy difference
      between two systems, 0 and 1, with configuration spaces omega(0), omega(1) of the
      same dimensionality. The method relies upon establishing a objective mapping
      between disjoint subsets gamma(i)(0) of omega(0) and corresponding disjoint
      subsets gamma(i)(1) of omega(1), and averaging a function of the ratio of
      configurational integrals over gamma(i)(0) and gamma(i)(1) with respect to the
      probability densities of the two systems. The mapped subsets gamma(i)(0) and
      gamma(i)(1) need not span the entire configuration spaces omega(0) and omega(1).
      The method is applied for the calculation of the excess chemical potential mu(ex)
      in a Lennard-Jones (LJ) fluid. In this case, omega(0) is the configuration space
      of a (N-1) real molecule plus one ideal-gas molecule system, while omega(1) is
      the configuration space of a N real molecule system occupying the same volume.
      Gamma(i)(0) and gamma(i)(1) are constructed from hyperspheres of the same radius
      centered at minimum-energy configurations of a set of "active" molecules lying
      within distance a from the ideal-gas molecule and the last real molecule,
      respectively. An algorithm is described for sampling gamma(i)(0) and gamma(i)(1)
      given a point in omega(0) or in omega(1). The algorithm encompasses three steps:
      "quenching" (minimization with respect to the active-molecule degrees of
      freedom), "mutation" (gradual conversion of the ideal-gas molecule into a real
      molecule, with simultaneous minimization of the energy with respect to the active
      molecule degrees of freedom), and "excitation" (generation of points on a
      hypersphere centered at the active-molecule energy minimum). These steps are also
      carried out in reverse, as required by the bijective nature of the mapping. The
      mutation step, which establishes a reversible mapping between energy minima with
      respect to the active degrees of freedom of systems 0 and 1, ensures that
      excluded volume interactions emerging in the process of converting the ideal-gas
      molecule into a real molecule are relieved through appropriate rearrangement of
      the surrounding active molecules. Thus, the insertion problem plaguing
      traditional methods for the calculation of chemical potential at high densities
      is alleviated. Results are presented at two state points of the LJ system for a
      variety of radii a of the active domain. It is shown that the estimated values of
      mu(ex) are correct in all cases and subject to an order of magnitude lower
      statistical uncertainty than values based on the same number of Widom [J. Chem.
      Phys. 39, 2808 (1963)] insertions at high fluid densities. Optimal settings for
      the new algorithm are identified and distributions of the quantities involved in
      it [number of active molecules, energy at the sampled minima of systems 0 and 1,
      and free-energy differences between subsets gamma(i)(0) and gamma(i)(1) that are
      mapped onto each other] are explored.

PMID- 16438570
TI  - On the calculation of time correlation functions by potential scaling.
AB  - We present and analyze a general method to calculate time correlation functions
      from molecular dynamics on scaled potentials for complex systems for which
      simulation is affected by broken ergodicity. Depending on the value of the
      scaling factor, correlations can be calculated for times that can be orders of
      magnitude longer than those accessible to direct simulations. We show that the
      exact value of the time correlation functions of the original system (i.e., with
      unscaled potential) can be obtained, in principle, using an action-reweighting
      scheme based on a stochastic path-integral formalism. Two tests (involving a
      bistable potential model and a dipeptide bond-vector orientational relaxation)
      are exemplified to showcase the strengths, as well as the limitations of the
      approach, and a procedure for the estimation of the time-dependent standard
      deviation error is outlined.

PMID- 16438571
TI  - Quantum computing based on vibrational eigenstates: pulse area theorem analysis.
AB  - In a recent paper [D. Babikov, J. Chem. Phys. 121, 7577 (2004)], quantum optimal
      control theory was applied to analyze the accuracy of quantum gates in a quantum
      computer based on molecular vibrational eigenstates. The effects of the
      anharmonicity parameter of the molecule, the target time of the pulse, and the
      penalty function on the accuracy of the qubit transformations were investigated.
      We demonstrate that the effects of all the molecular and laser-pulse parameters
      can be explained utilizing the analytical pulse area theorem, which originates
      from the standard two-level model. Moreover, by analyzing the difference between
      the optimal control theory results and those obtained using the pulse area
      theorem, it is shown that extremely high quantum gate fidelity can be achieved
      for a qubit system based on vibrational eigenstates.

PMID- 16438572
TI  - General-model-space state-universal coupled-cluster methods for excited states:
      diagonal noniterative triple corrections.
AB  - The recently developed multireference, general-model-space, state-universal
      coupled-cluster approach considering singles and doubles (GMS SU CCSD) has been
      extended to account perturbatively for triples, similar to the ubiquitous single
      reference CCSD(T) method. The effectiveness of this extension in handling of
      excited states and its ability to account for the static and nondynamic
      correlation effects when considering spin- and/or space-symmetry degenerate
      levels within the spin-orbital formalism is examined on the example of low-lying
      excitation energies of the C2, N2, and CO molecules and a comparison is made with
      the (N,N)-CCSD method used for the same purpose. It is shown that while the
      triple corrections are very effective in improving the absolute energies, they
      have only a modest effect on the corresponding excitation energies, which may be
      even detrimental if both the ground- and excited-state levels cannot be given a
      balanced treatment. While the triple corrections help to avoid the symmetry
      breaking effects arising due to the use of the spin-orbital formalism, they are
      much less effective in this regard than the (N,N)-CCSD approach.

PMID- 16438573
TI  - Chirality-induced signals in coherent multidimensional spectroscopy of excitons.
AB  - The nonlocal second- and third-order susceptibilities of an isotropic ensemble of
      aggregates are calculated by solving the nonlinear exciton equations which map
      the system into coupled anharmonic oscillators. Both electric and magnetic
      contributions are included using the minimal-coupling Hamiltonian. The various
      tensor components are evaluated to first order in the optical wave vector k.
      Additional structural information about the interchromophore distances, which is
      not accessible through zeroth-order contributions (the dipole approximation), is
      contained to the first order in k. New resonant second- and third-order signals
      predicted for chiral molecules provide multidimensional extensions of circular
      dichroism spectroscopy. Numerical simulations demonstrate the sensitivity of
      third-order signals to the secondary structural motiffs of peptides.

PMID- 16438574
TI  - Quantum-mechanical evaluation of the Boltzmann operator in correlation functions
      for large molecular systems: a multilayer multiconfiguration time-dependent
      Hartree approach.
AB  - It is shown that the Boltzmann operator in time correlation functions for complex
      molecular systems can be evaluated in a numerically exact way employing the
      multilayer formulation of the multiconfiguration time-dependent Hartree theory in
      combination with Monte Carlo importance sampling techniques. The performance of
      the method is illustrated by selected applications to photoinduced intervalence
      electron transfer reactions in the condensed phase. Furthermore, the validity of
      approximate schemes to evaluate the Boltzmann is discussed.

PMID- 16438575
TI  - Reconciling semiclassical and Bohmian mechanics. II. Scattering states for
      discontinuous potentials.
AB  - In a previous paper [B. Poirier, J. Chem. Phys. 121, 4501 (2004)] a unique
      bipolar decomposition, psi = psi1 + psi2, was presented for stationary bound
      states Psi of the one-dimensional Schrodinger equation, such that the components
      psi1 and psi2 approach their semiclassical WKB analogs in the large action limit.
      Moreover, by applying the Madelung-Bohm ansatz to the components rather than to
      Psi itself, the resultant bipolar Bohmian mechanical formulation satisfies the
      correspondence principle. As a result, the bipolar quantum trajectories are
      classical-like and well behaved, even when psi has many nodes or is wildly
      oscillatory. In this paper, the previous decomposition scheme is modified in
      order to achieve the same desirable properties for stationary scattering states.
      Discontinuous potential systems are considered (hard wall, step potential, and
      square barrier/well), for which the bipolar quantum potential is found to be zero
      everywhere, except at the discontinuities. This approach leads to an exact
      numerical method for computing stationary scattering states of any desired
      boundary conditions, and reflection and transmission probabilities. The
      continuous potential case will be considered in a companion paper [C. Trahan and
      B. Poirier, J. Chem. Phys. 124, 034116 (2006), following paper].

PMID- 16438576
TI  - Reconciling semiclassical and Bohmian mechanics. III. Scattering states for
      continuous potentials.
AB  - In a previous paper [B. Poirier, J. Chem. Phys. 121, 4501 (2004)] a unique
      bipolar decomposition psi = psi1 + psi2 was presented for stationary bound states
      Psi of the one-dimensional Schrodinger equation, such that the components psi1
      and psi2 approach their semiclassical WKB analogs in the large-action limit. The
      corresponding bipolar quantum trajectories, as defined in the usual Bohmian
      mechanical formulation, are classical-like and well behaved, even when Psi has
      many nodes or is wildly oscillatory. A modification for discontinuous potential
      stationary scattering states was presented in a second, companion paper [C.
      Trahan and B. Poirier, J. Chem. Phys.124, 034115 (2006), previous paper], whose
      generalization for continuous potentials is given here. The result is an exact
      quantum scattering methodology using classical trajectories. For additional
      convenience in handling the tunneling case, a constant-velocity-trajectory
      version is also developed.

PMID- 16438577
TI  - Doppler effect in fluorine K-Auger line produced in electron-induced core
      ionization of SF6.
AB  - An experimental evidence is reported on the observation of the Doppler effect in
      fluorine K-Auger line emitted from a core-ionized SF6 molecule under an impact of
      16 keV electrons. The emitting source of the Auger line is found to acquire a
      kinetic energy of 4.7+/-0.3 keV. We propose that such large energy is released
      from the Coulomb repulsion taking place between F+ and SF5+ fragment ions under
      influence of an intense focusing field of the incident electrons. In the presence
      of the Coulomb field of these ions, the Auger line obtains a polarization P =
      76%+/-7%.

PMID- 16438578
TI  - Spectroscopic analysis of small organic molecules: a comprehensive near-edge x
      ray-absorption fine-structure study of C6-ring-containing molecules.
AB  - We report high-resolution C 1s near-edge x-ray-absorption fine-structure (NEXAFS)
      spectra of the C6-ring-containing molecules benzene (C6H6), 1,3- and 1,4
      cyclohexadiene (C6H8), cyclohexene (C6H10), cyclohexane (C6H12), styrene (C8H8),
      and ethylbenzene (C8H10) which allow us to examine the gradual development of
      delocalization of the corresponding pi electron systems. Due to the high
      experimental resolution, vibrational progressions can be partly resolved in the
      spectra. The experimental spectra are compared with theoretical NEXAFS spectra
      obtained from density-functional theory calculations where electronic final-state
      relaxation is accounted for. The comparison yields very good agreement between
      theoretical spectra and experimental results. In all cases, the spectra can be
      described by excitations to pi*- and sigma*-type final-state orbitals with
      valence character, while final-state orbitals of Rydberg character make only
      minor contributions. The lowest C 1s-->1pi* excitation energy is found to agree
      in the (experimental and theoretical) spectra of all molecules except for 1,3
      cyclohexadiene (C6H8) where an energy smaller by about 0.6 eV is obtained. The
      theoretical analysis can explain this result by different binding properties of
      this molecule compared to the others.

PMID- 16438579
TI  - A systematic multireference perturbation-theory study of the low-lying states of
      SiC3.
AB  - The three known lowest-energy isomers of SiC(3), two cyclic singlets (2s and 3s)
      and a linear triplet (1t), have been reinvestigated using multireference second
      order perturbation theory (MRPT2). The dependence of the relative energies of the
      isomers upon the quality of the basis sets and the sizes of the reference active
      spaces is explored. When using a complete-active-space self-consistent-field
      reference wave function with 12 electrons in 11 orbitals [CASSCF (12, 11)]
      together with basis sets that increase in size up to the correlation-consistent
      polarized core-valence quadruple zeta basis set (cc-pCVQZ), the MRPT2 method
      consistently predicts the linear triplet to be the most stable isomer. A new
      parallel direct determinant MRPT2 code has been used to systematically explore
      reference spaces that vary in size from CASSCF (8,8) to full optimized reaction
      space [FORS or CASSCF (16,16)] with the cc-pCVQZ basis. It is found that the
      relative energies of the isomers change substantially as the active space is
      increased. At the best level of theory, MRPT2 with a full valence FORS reference,
      the 2s isomer is predicted to be more stable than 3s and 1t by 4.7 and 2.2
      kcal/mol, respectively.

PMID- 16438580
TI  - Coherent phase control of the product branching ratio in the photodissociation of
      dimethylsulfide.
AB  - Coherent phase control of the photodissociation reaction of the dimethylsulfide
      has been achieved by means of quantum-mechanical interference between one- and
      three-photon transitions. Dimethylsulfide was irradiated by fundamental and
      frequency-tripled outputs of a visible laser (600.5-602.5 nm), simultaneously to
      yield CH3S+ and CH3SCH2+ fragment ions. The branching ratio of the two product
      channels could be modulated with variation of the phase difference between the
      light fields. This accounted for the difference between the molecular phases of
      the two product channels. The phase lag was observed to have a maximum value of 8
      degrees at 601.5 nm. This is the first result of a selective bond breaking in a
      polyatomic molecule by the coherent phase control.

PMID- 16438581
TI  - Quantum dynamics of Ne-Br2 vibrational predissociation: the role of continuum
      resonances as doorway states.
AB  - Wave-packet simulations of the Ne-Br2(B,upsilon') vibrational predissociation
      dynamics in the range upsilon' = 16-29 are reported. The aim is to interpret
      recent time-dependent pump-probe experiments [Cabrera et al., J. Chem. Phys. 123,
      054311 (2005)]. Good agreement is found between the calculated and the
      experimental lifetimes corresponding to decay of the Ne-Br2(B,upsilon') initial
      state and to appearance of Br2(B,upsilon<upsilon') products. The simulations show
      that up to upsilon' approximately 22 the dynamics is dominated by direct
      predissociation, while for higher upsilon' levels an indirect intramolecular
      vibrational relaxation mechanism of dissociation becomes increasingly important.
      Such a mechanism occurs via coupling of the initial state in the upsilon'
      vibrational manifold to nearly degenerate resonances embedded in the continuum of
      the lower upsilon<upsilon' manifolds, which act as intermediate doorway states to
      dissociation. The role of the intermediate resonances manifests itself in
      multiexponential behavior and oscillations in the time-dependent population
      curves associated with the initial complex state, the final product states, and
      the Ne-Br2(B,upsilon<upsilon') intermediate complexes. Analysis of the Ne
      Br2(B,upsilon<upsilon') intermediate population shows that the continuum
      resonances are supported by centrifugal barriers involving excitation of the
      internal rotation of the complex. We find that the coupling between the
      intermediate state resonances and the continuum product state wave functions
      extend to Ne-Br2 distances greater than 15 angstroms. In the light of the
      results, a structure of the spectrum of continuum resonances is suggested and
      discussed.

PMID- 16438582
TI  - On the photophysics of all-trans polyenes: hexatriene versus octatetraene.
AB  - The disparate photophysical behavior of trans-1,3,5-hexatriene (nonfluorescent)
      and trans-1,3,5,7-octatetraene (with two fluorescence emissions) in the gas phase
      is explained in terms of the tendency of their 1B(u) excited states to rotate
      about their terminal carbon-carbon single bonds in order to adopt a quasiplanar
      molecular form of lower energy than the 1B(u) state in the parent all-trans
      structure. The origin of their disparate photophysical behavior is that such a
      transformation is subject to a small energy barrier in octatetraene; the barrier
      produces two minima (two fluorescence emissions) in the corresponding potential
      energy curve. Instead of an energy barrier, hexatriene gives a 1,3-diene species
      which falls to the ground state so rapidly that no emission is produced.

PMID- 16438583
TI  - The electronic spectrum of AgCl2: ab initio benchmark versus density-functional
      theory calculations on the lowest ligand-field states including spin-orbit
      effects.
AB  - The X 2pi(g), 2sigma(g)+, and 2delta(g) states of AgCl2 have been studied through
      benchmark ab initio complete active space self-consistent field plus second-order
      complete active space multireference Moller-Plesset algorithm (CASSCF+CASPT2) and
      complete active space self-consistent field plus averaged coupled pair functional
      (CASSCF+ACPF) and density-functional theory (DFT) calculations using especially
      developed basis sets to study the transition energies, geometries, vibrational
      frequencies, Mulliken charges, and spin densities. The spin-orbit (SO) effects
      were included through the effective Hamiltonian formalism using the LambdaSSigma
      ACPF energies as diagonal elements. At the ACPF level, the ground state is 2pi(g)
      in contradiction with ligand-field theory, SCF, and large CASSCF; the adiabatic
      excitation energies for the 2sigma(g)+ and 2delta(g) states are 1640 and 18,230
      cm(-1), respectively. The inclusion of the SO effects leads to a pure omega =
      32(2pi(g)) ground state, a omega = 12 (66%2pi(g) and 34%2sigma(g)+) A state, a
      omega = 12 (34%2pi(g) and 66%2sigma(g)+) B state, a omega = 52(2delta(g))C state,
      and a omega = 32(99%2delta(g))D state. The X-A, X-B, X-C, and X-D transition
      energies are 485, 3715, 17 246, and 20 110 cm(-1), respectively. The B97-2,
      B3LYP, and PBE0 functionals overestimate by approximately 100% the X 2pi(g)
      2sigma(g)+T(e) but provide a qualitative energetic ordering in good agreement
      with ACPF results. B3LYP with variable exchange leads to a 42% optimal Hartree
      Fock exchange for transition energies but all equilibrium geometries get
      worsened. Asymptotic corrections to B3LYP do not provide improved values. The
      nature of the bonding in the X 2pi(g) state is very different from that of CuCl2
      since the Mulliken charge on the metal is 1.1 while the spin density is only
      0.35. DFT strongly delocalizes the spin density providing even smaller values of
      around 0.18 on Ag not only for the ground state, but also for the 2sigma(g)+
      state.

PMID- 16438584
TI  - New exchange-Coulomb N2-Ar potential-energy surface and its comparison with other
      recent N2-Ar potential-energy surfaces.
AB  - The reliability of five N2-Ar potential-energy surfaces in representing the N2-Ar
      interaction has been investigated by comparing their abilities to reproduce a
      variety of experimental results, including interaction second viral coefficients,
      bulk transport properties, relaxation phenomena, differential scattering cross
      sections, and the microwave and infrared spectra of the van der Waals complexes.
      Four of the surfaces are the result of high-level ab initio quantal calculations;
      one of them utilized fine tuning by fitting to microwave data. To date, these
      four potential-energy surfaces have only been tested against experimental
      microwave data. The fifth potential-energy surface, based upon the exchange
      Coulomb potential-energy model for the interaction of closed-shell species, is
      developed herein: it is a combination of a damped dispersion energy series and ab
      initio calculations of the Heitler-London interaction energy, and has adjustable
      parameters determined by requiring essentially simultaneous agreement with
      selected quality interaction second viral coefficient and microwave data.
      Comparisons are also made with the predictions of three other very good
      literature potential-energy surfaces, including the precursor of the new exchange
      Coulomb potential-energy surface developed here. Based upon an analysis of a
      large body of information, the new exchange-Coulomb and microwave-tuned ab initio
      potential-energy surfaces provide the best representations of the N2-Ar
      interaction; nevertheless, the other potential-energy surfaces examined still
      have considerable merit with respect to the prediction of specific properties of
      the N2-Ar van der Waals complex. Of the two recommended surfaces, the new
      exchange-Coulomb surface is preferred on balance due to its superior predictions
      of the effective cross sections related to various relaxation phenomena, and to
      its reliable, and relatively simple, representation of the long-range part of the
      potential-energy surface. Moreover, the flexibility still inherent in the
      exchange-Coulomb potential form can be further exploited, if required, in future
      studies of the N2-Ar interaction.

PMID- 16438586
TI  - The low-lying electronic states of nickel cyanide and isocyanide: A theoretical
      investigation.
AB  - At different levels of coupled cluster theory optimum structures, energetics, and
      harmonic vibrational frequencies for several low-lying doublet and quartet
      electronic states of linear NiCN and NiNC were studied using four contracted
      Gaussian basis sets, ranging from Ni[6s5p4d2f], CN[4s3p2d] to Ni[8s7p5d3f2g1h],
      CN[5s4p3d2f1g]. The most reliable predictions were obtained with a relativistic
      Douglas-Kroll restricted open-shell-based coupled cluster method including
      singles, doubles, and perturbative triple excitations [DK-R/UCCSD(T)]. This level
      of theory was used in conjunction with correlation-consistent polarized valence
      Douglas-Kroll recontracted quadruple-zeta basis sets (cc-pVQZDK). The energetic
      ordering of the electronic states of NiCN is predicted to be 2delta < 2sigma+ <
      2pi < 4delta < 4pi and that of NiNC is 2delta approximately 2sigma+ < 2pi <
      4delta < 4pi < 4sigma-. Our theoretical investigation supports the assignment of
      the ground-state term symbol, the Ni-C stretching frequency, and the bending
      frequency for the ground electronic state of NiCN by Kingston et al. [J. Mol.
      Spectrosc. 215, 106 (2002)] and by Sheridan and Ziurys [J. Chem. Phys. 118, 6370
      (2003)]. The predicted structure of the 2delta ground state of NiCN, r(e)(Ni-C) =
      1.822 angstroms and r(e)(C-N) = 1.167 angstroms, at DK-R/UCCSD(T)/cc-pVQZDK shows
      excellent agreement with the experimentally determined Ni-C bond length of 1.826
      A and less satisfactory agreement for the C-N bond length of 1.153 angstroms [J.
      Chem. Phys. 118, 6370 (2003)]. It is also concluded that the metal-to-ligand pi
      back donation is weak or negligible. Additionally, we found that on the 2delta
      surface the linear cyanide isomer lies lower in energy than the linear isocyanide
      isomer by 12.2 kcal mol(-1).

PMID- 16438585
TI  - A photodissociation study of CH2BrCl in the A-band using the time-sliced ion
      velocity imaging method.
AB  - Employing a high-resolution (velocity resolution deltanu/nu<1.5%) time-sliced ion
      velocity imaging apparatus, we have examined the photodissociation of CH2BrCl in
      the photon energy range of 448.6-618.5 kJ/mol (193.3-266.6 nm). Precise
      translational and angular distributions for the dominant Br(2P32) and Br(2P12)
      channels have been determined from the ion images observed for Br(2P32) and
      Br(2P12). In confirmation with the previous studies, the kinetic-energy
      distributions for the Br(2P12) channel are found to fit well with one Gaussian
      function, whereas the kinetic- energy distributions for the Br(2P32) channel
      exhibit bimodal structures and can be decomposed into a slow and a fast Gaussian
      component. The observed kinetic-energy distributions are consistent with the
      conclusion that the formation of the Br(2P32) and Br(2P12) channels takes place
      on a repulsive potential-energy surface, resulting in a significant fraction
      (0.40-0.47) of available energy to appear as translational energy for the photo
      fragments. On the basis of the detailed kinetic-energy distributions and
      anisotropy parameters obtained in the present study, together with the specific
      features and relative absorption cross sections of the excited 2A', 1A", 3A',
      4A', and 2A" states estimated in previous studies, we have rationalized the
      dissociation pathways of CH2BrCl in the A-band, leading to the formation of the
      Br(2P32) and Br(2P12) channels. The analysis of the ion images observed at 235 nm
      for Cl(2P(32,12)) provides strong evidence that the formation of Cl mainly arises
      from the secondary photodissociation process CH2Cl + hnu --> CH2 + Cl.

PMID- 16438587
TI  - Comparing reactions of H and Cl with C-H stretch-excited CHD3.
AB  - We report the methyl radical product state distributions for the reactions of H
      and Cl with CHD3(nu1 = 1,2) at collision energies of 1.53 and 0.18 eV,
      respectively. Both reactions demonstrate mode selectivity. The resulting state
      distributions from the H+CHD3(nu1 = 1,2) reactions are well described by a
      spectator model. The reactions Cl + CHD3(nu1 = 1,2) exhibit similar behavior, but
      in some aspects the spectator model breaks down. We attribute this breakdown to
      enhanced intramolecular vibrational redistribution in the Cl + CHD3(nu1 = 1,2)
      reactions compared to the H + CHD3(nu1 = 1,2) reactions, caused by the
      interaction of the slower Cl atom with the vibrationally excited CHD3, which is
      promoted either by its longer collision duration, its stronger coupling, or both.

PMID- 16438588
TI  - Electronic spectra and photodissociation of vinyl chloride: a symmetry-adapted
      cluster configuration interaction study.
AB  - The vertical absorption spectrum and photodissociation mechanism of vinyl
      chloride (VC) were studied by using symmetry-adapted cluster configuration
      interaction theory. The important vertical pi --> pi* excitation was intensively
      examined with various basis sets up to aug-cc-pVTZ augmented with appropriate
      Rydberg functions. The excitation energy for pi --> pi* transition obtained in
      the present study, 6.96 eV, agrees well with the experimental value, 6.7-6.9 eV.
      Calculated excitation energies along with the oscillator strengths clarify that
      the main excitation in VC is the pi --> pi* excitation. Contrary to the earlier
      theoretical reports, the results obtained here support that the C-Cl bond
      dissociation takes place through the n(Cl-)sigma(C-Cl)* state.

PMID- 16438589
TI  - Accurate ab initio potential for the Na+...I* complex.
AB  - High-level ab initio calculations employing the multireference configuration
      interaction and coupled clusters methods with a correlation-consistent sequence
      of basis sets have been used to obtain accurate potential energy curves for the
      complex of the sodium cation with the iodine atom. Potential curves for the first
      two electronic Lambda-S states have very different characters: the potential for
      the 2pi state has a well depth of approximately 10 kcal/mol, while the 2sigma
      state is essentially unbound. This difference is rationalized in terms of the
      anisotropic interaction of the quadrupole moment of the iodine atom with the
      sodium cation, which is stabilizing in the case of the 2pi state and
      destabilizing in the case of the 2sigma state. The effects of spin-orbit coupling
      have been accounted for with both ab initio and semiempirical approaches, which
      have been found to give practically the same results. Inclusion of spin-orbit
      interactions does not affect the X(omega = 32) ground state, which retains its
      2pi character, but it results in two omega = 12 spin-orbit states, with mixed
      2sigma and 2pi characters and binding energies roughly half of that of the ground
      spin-orbit state. Complete basis set (CBS) extrapolations of potential curves,
      binding energies, and equilibrium geometries were also performed, and used to
      calculate a number of rovibronic parameters for the Na+...I* complex and to
      parameterize model potentials. The final CBS-extrapolated and zero-point
      vibrational energy-corrected binding energy is 10.2 kcal/mol. Applications of the
      present results for simulations of NaI photodissociation femtosecond spectroscopy
      are discussed.

PMID- 16438590
TI  - Elastic and charge transfer processes in H+ + CO collisions.
AB  - Proton and hydrogen atom time-of-flight spectra in collision energy range of
      E(trans) = 9.5-30 eV show that the endoergic charge transfer process in the H+ +
      CO system is almost an order of magnitude less probable than the elastic
      scattering [G. Niedner-Schatteburg and J. P. Toennies, Adv. Chem. Phys. LXXXII,
      553 (1992)]. Ab initio computations at the multireference configuration
      interaction level have been performed to obtain the ground- and several low-lying
      excited electronic state potential energy curves in three different molecular
      orientations namely, H+ approaching the O-end and the C-end (collinear), and H+
      approaching the CO molecule in perpendicular configuration with fixed CO
      internuclear distance. Nonadiabatic coupling terms between the ground electronic
      state (H+ + CO) and the three low-lying excited electronic states (H + CO+) have
      been computed and the corresponding diabatic potentials have been obtained. A
      time-dependent wavepacket dynamics study is modeled first involving only the
      ground and the first excited states and then involving the ground and the three
      lowest excited states at the collision energy of 9.5 eV. The overall charge
      transfer probability have been found to be approximately 20%-30% which is in
      qualitative agreement with the experimental findings.

PMID- 16438591
TI  - Recombination of photodissociated iodine: a time-resolved x-ray-diffraction
      study.
AB  - A time-resolved x-ray-diffraction experiment is presented that aims to study the
      recombination of laser-dissociated iodine molecules dissolved in CCl4. This
      process is monitored over an extended time interval from pico- to microseconds.
      The variations of atom-atom distances are probed with a milliangstrom resolution.
      A recent theory of time-resolved x-ray diffraction is used to analyze the
      experimental data; it employs the correlation function approach of statistical
      mechanics. The most striking outcome of this study is the experimental
      determination of time-dependent I-I atom-atom distribution functions. The
      structure of the CCl4 solvent changes simultaneously; the solvent thus appears as
      a reaction partner rather than an inert medium hosting it. Thermal expansion of
      the system is nonuniform in time, an effect due to the presence of the acoustic
      horizon. One concludes that a time-resolved x-ray diffraction permits real-time
      visualization of solvent and solute motions during a chemical reaction.

PMID- 16438592
TI  - Path-integral Monte Carlo simulation of the recombination of two Al atoms
      embedded in parahydrogen.
AB  - We report the use of path-integral Monte Carlo (PIMC) simulations in the study of
      the stability against recombination of two Al atoms trapped in solid parahydrogen
      (pH2) at 4 K. The many-body interactions involving open-shell Al atoms are
      described with a pairwise additive Hamiltonian model. To estimate the lifetime
      against recombination, we use PIMC simulations to define an effective potential
      averaged over the position of the pH2 molecules, followed by a transition-state
      treatment. Different initial embedding sites are explored. If the initial
      substitution sites are within a distance of approximately 13 bohrs, the Al atoms
      will significantly distort the lattice structure to allow recombination, with an
      accompanying release of energy during the process. For substitution distances
      longer than approximately 14 bohrs, the dispersion of Al atoms is shown to be
      metastable, with lifetimes varying from approximately 30 min to several days. The
      electronic anisotropy is a factor that helps to stabilize the dispersion.

PMID- 16438593
TI  - Molecular-dynamics simulations and master-equation description of a chemical wave
      front: effects of density and size of reaction zone on propagation speed.
AB  - We compare the master-equation description and molecular-dynamics simulations of
      a chemical wave front. We find that the front propagation speed depends on the
      number of particles in the reaction zone. For the master equation the dependence
      follows the well-known logarithmic prediction obtained when introducing a cutoff
      into the macroscopic reaction-diffusion equation. The molecular-dynamics
      simulations reveal that the logarithmic law is compromised for dense fluids.

PMID- 16438594
TI  - Au and Pd atoms adsorbed on pure and Ti-doped SiO2/Mo(112) films.
AB  - The interaction of Pd and Au atoms with a silica surface and SiO2Mo(112)
      ultrathin films has been studied with periodic density-functional theory
      generalized gradient approximation calculations. On both unsupported and
      supported silica, Pd and Au are weakly bound. No charge transfer occurs to the
      empty Pd and Au orbitals. Differently from Au, Pd can easily penetrate with
      virtually no barrier into the hexagonal rings of the supported silica film and
      binds strongly at the SiO2-Mo interface. The same process for Au implies
      overcoming a barrier of 0.9 eV. Completely different is the behavior of Ti-doped
      silica films. Au forms a direct covalent bond with substitutional Ti at the
      expense of the Ti...O-Mo interface bond which breaks. The global process is
      exothermic by 1 eV and nonactivated, showing that Ti doping results in solid
      anchoring points for the adsorbed Au atoms and for nucleation and growth of small
      gold particles. The effect of Ti doping is less pronounced for Pd but still
      visible with substantial enhancement of the Pd adsorption strength.

PMID- 16438595
TI  - Correlation induced insulator to metal transition: a systematic density
      functional study on highly doped n-type trans-polyacetylene.
AB  - Since its discovery in 1977, a number of quantum chemical calculations have been
      attempted to simulate the metallic state of highly doped trans-polyacetylene.
      These simulations have focused on the possible closure of the band gap at high
      doping level due to a charge-induced elimination of Peierls distortion; however,
      conclusive demonstration of a metallic state has not been achieved. The present
      study presents density functional theory calculations of the band structure of
      highly doped trans-polyacetylene with explicit inclusion of the metal atoms in a
      one-dimensional periodic structure. The results indicate (i) small lattice
      dimerization, i.e., remnant of Peierls distortion exists even in the heavily
      doped trans-polyacetylene sample, (ii) charge induced closure of the Peierls gap
      is not a necessary condition to arrive at a metallic state in such systems, and
      (iii) electronic correlation, as described at the density functional theory
      level, with a charge induced small Peierls distortion is sufficient to achieve
      metallic state of highly doped n-type trans-polyacetylene even in one dimension.
      Furthermore, comparison of functionals that include differing degrees of electron
      correlation suggest that correlation promotes formation of the metallic state.

PMID- 16438596
TI  - Calculation of the force between surfaces coated with grafted molecules by
      molecular simulation.
AB  - We discuss the calculation of the force between surfaces coated with anchored
      molecules. This force is related to the pressure and can therefore be calculated
      by the usual means: either by summing over all surface-particle forces or from
      the virial. However, we argue that the grafting of the molecule must be included
      by means of a restraining potential-otherwise, nonphysical results can be
      obtained, such as the appearance of a net force even when the particles are
      spaced very far away. Bond-stretching potentials are also required if the virial
      is employed.

PMID- 16438597
TI  - Surface anchoring of rodlike molecules on corrugated substrates.
AB  - We studied the mechanism of surface anchoring of rodlike molecules on substrates
      with the surfaces corrugated at molecular scale by molecular-dynamics simulation.
      We constructed a model for substrates that can have anisotoropic topographical
      patterns such as corrugation. The structural and thermodynamic properties of
      rodlike molecules on the corrugated surfaces, including the elastic and anchoring
      properties, were calculated and the influence of the surface structure on the
      anchoring was discussed. We found that the rodlike molecules are aligned along
      the grooves of the corrugated surfaces guided by the anisotropic molecular
      interaction between the molecules and the corrugated surface. The strength of
      anchoring was found to be increased when the period of corrugation is decreased
      at molecular level.

PMID- 16438598
TI  - Characterization of molecular disorder in vapor-deposited thin films of aluminum
      tris(quinoline-8-olate) by one-dimensional 27Al NMR under magic angle spinning.
AB  - Aluminum tris (quinoline-8-olate) (Alq3) is used as an electron-transport layer
      in organic light-emitting diodes. The material can be obtained in a wide range of
      different solid phases, both crystalline and amorphous, by deposition from the
      vapor phase or from solution under controlled conditions. While the structure of
      the crystalline polymorphs of Alq3 has been investigated thoroughly by x-ray
      diffraction as well as solid-state NMR, very little information is currently
      available on the amount of structural disorder in the amorphous forms of Alq3. In
      the present contribution, we report the use of 27Al NMR spectroscopy in the solid
      state under magic angle spinning to extract such information from amorphous vapor
      deposits of Alq3. The NMR spectra obtained from these samples exhibit different
      degrees of broadening, reflecting distributions of the electric-field gradient
      tensor at the site of the aluminum ion. These distributions can be obtained from
      the NMR spectra by solving the corresponding inverse problem. From these results,
      the magnitude of structural disorder in terms of molecular geometry has been
      estimated by density-functional theory calculations. It was found that the
      electric-field gradient anisotropy delta follows a bimodal distribution. Its
      majority component is centered around delta values comparable to the meridianal
      alpha crystal polymorph and has a width of about 10%, corresponding to
      distortions of the molecular geometry of a few degrees in the orientation of the
      ligands. Alq3 samples obtained at higher deposition rates exhibit higher degrees
      of disorder. The minor component, present at about 7%, has a much smaller
      anisotropy, suggesting that it may be due to the facial isomer of Alq3.

PMID- 16438599
TI  - Ultrathin Rh films on Ru(0001): oxidation in confinement.
AB  - Ultrathin rhodium films with a thickness ranging from 1 to a few monolayers were
      deposited on a single-crystal Ru(0001) surface in order to investigate the
      oxidation behavior of ultrathin epitaxial films on a dissimilar substrate. It is
      found that rhodium grows on Ru(0001) initially layer by layer, adapting the in
      plane lattice parameters of Ru(0001). When exposing Rh films to oxygen
      environment (approximately 4.8 x 10(6) L O2 exposure) at 660 K, 2-4 ML Rh films
      form a surface oxide composed of (9 x 9) O-Rh-O trilayers. Quite in contrast,
      oxidation of the 1 ML RhRu(0001) film leads to a poorly ordered oxide with a
      rutile structure reminiscent of RuO2(110) on Ru(0001). The oxidized 1 ML
      RhRu(0001) film contains much more oxygen than the oxidized thicker Rh films.
      Lower temperatures (535 K) and high doses of oxygen lead to a (1 x 1)-O overlayer
      on the 1 ML RhRu(0001) surface, whose atomic geometry resembles closely that of
      the (1 x 1)-O phase on clean Ru(0001).

PMID- 16438600
TI  - Elastic light scattering from nanoparticles by monochromatic vacuum-ultraviolet
      radiation.
AB  - Elastic light scattering is reported using monochromatic vacuum-ultraviolet
      radiation to study free, spherical silica nanoparticles prepared by approaches
      from colloidal chemistry, with diameters between 100 and 240 nm. The colloidal
      nanoparticles of defined size are transferred from an aqueous solution into the
      gas phase using a particle beam experiment. After focusing of the particle beam
      by an aerodynamic lens, the scattered light from monochromatic synchrotron
      radiation is measured. Angle-resolved elastically scattered light is detected,
      showing a strong forward-scattering component. Additional evidence for the
      detection of elastically scattered light comes from plotting the scattered light
      intensity as a function of the dimensionless parameter qR, where q is the
      magnitude of the scattering wave vector and R is the particle radius. This yields
      different power-law regimes that are assigned to scattering from the surface and
      the bulk of the nanoparticles. Furthermore, there is evidence for modulations in
      the scattered light intensity as a function of scattering angle, which is clearly
      distinguished from the forward-scattering component. The experimental results are
      compared to Mie scattering simulations for isolated particles, yielding general
      agreement with the experimental results. Deviations from Mie simulations are
      observed for samples consisting of significant amounts of aggregates. The present
      results indicate that the optical properties of free nanoparticles are
      sensitively probed by vacuum-ultraviolet radiation.

PMID- 16438601
TI  - A generalized quantum chemical approach for elastic and inelastic electron
      transports in molecular electronics devices.
AB  - A generalized quantum chemical approach for electron transport in molecular
      devices is developed. It allows one to treat devices where the metal electrodes
      and the molecule are either chemically or physically bonded on equal footing. An
      extension to include the vibration motions of the molecule has also been
      implemented which has produced the inelastic electron-tunneling spectroscopy of
      molecular electronics devices with unprecedented accuracy. Important information
      about the structure of the molecule and of metal-molecule contacts that are not
      accessible in the experiment are revealed. The calculated current-voltage (I-V)
      characteristics of different molecular devices, including benzene-1,4-dithiolate,
      octanemonothiolate [H(CH2)8S], and octanedithiolate [S(CH2)8S] bonded to gold
      electrodes, are in very good agreement with experimental measurements.

PMID- 16438602
TI  - Catalytic spatiotemporal thermal patterns during CO oxidation on cylindrical
      surfaces: experiments and simulations.
AB  - Dynamics of spatiotemporal thermal patterns during the catalytic CO oxidation
      over Pd supported on a glass-fiber catalytic cloth rolled into a tube of 20 mm
      diameter and 80 mm length has been studied in a continuous flow reactor by IR
      thermography. A specially designed aluminum mirror built in the reactor provided
      image of the entire surface of the horizontally held catalytic tube. With flow in
      the main axial direction and through the tube surface, we observed periodic
      motions of a pulse, which was born downstream and propagated upstream. The
      temperature pulse motion was accompanied by conversion oscillations of CO2. With
      flow in the main axial direction, parallel to the surface, we observed a
      stationary hot zone after an oscillatory transient. These patterns can be
      simulated with a plug-flow-reactor-like heterogeneous reactor model that
      incorporates previously determined kinetic and transport parameters.

PMID- 16438603
TI  - Theoretical study of vibration-phonon coupling of H adsorbed on a Si(100)
      surface.
AB  - In this paper a perturbation-theory study of vibrational lifetimes for the
      bending and stretching modes of hydrogen adsorbed on a Si(100) surface is
      presented. The hydrogen-silicon interaction is treated with a semiempirical bond
      order potential. Calculations are performed for H-Si clusters of different sizes.
      The finite lifetime is due to vibration-phonon coupling, which is assumed to be
      linear or bilinear in the phonon and nonlinear in the H-Si stretching and bending
      modes. Lifetimes and vibrational transition rates are evaluated with one- and two
      phonon processes taken into account. Temperature effects are also discussed. In
      agreement with the experiment and previous theoretical treatment it is found that
      the H-Si (upsilon(s) = 1) stretching vibration decays on a nanosecond timescale,
      whereas for the H-Si (upsilon(b) = 1) bending mode a picosecond decay is
      predicted. For higher-excited vibrations, simple scaling laws are found if the
      excitation energies are not too large. The relaxation mechanisms for the excited
      H-Si stretching and the H-Si bending modes are analyzed in detail.

PMID- 16438604
TI  - Xenon porometry at room temperature.
AB  - Xenon porometry is a method in which porous material is immersed in a medium and
      the properties of the material are studied by means of 129Xe nuclear magnetic
      resonance (NMR) of xenon gas dissolved in the medium. For instance, the chemical
      shift of a particular signal (referred to as signal D) arising from xenon inside
      small pockets formed in the pores during the freezing of the confined medium is
      highly sensitive to the pore size. In the present study, we show that when
      naphthalene is used as the medium the pore size distribution of the material can
      be determined by measuring a single one-dimensional spectrum near room
      temperature and converting the chemical shift scale of signal D to the pore
      radius scale by using an experimentally determined correlation. A model has been
      developed that explains the curious behavior of the chemical shift of signal D as
      a function of pore radius. The other signals of the spectra measured at different
      temperatures have also been identified, and the influence of xenon pressure on
      the spectra has been studied. For comparison, 129Xe NMR spectra of pure xenon gas
      adsorbed to porous materials have been measured and analyzed.

PMID- 16438605
TI  - Calculations of crystal-melt interfacial free energies by nonequilibrium work
      measurements.
AB  - We developed a multistep thermodynamic perturbation method to compute the
      interfacial free energies by nonequilibrium work measurements with cleaving
      potential procedure. Using this method, we calculated the interfacial free
      energies of different crystal orientations for the Lennard-Jones system. Our
      results are in good agreement with the results by thermodynamic integration
      method. Compared with thermodynamic integration method, the multistep
      thermodynamic perturbation method is more efficient. For each stage of the
      cleaving process, only a few thermodynamic perturbation steps are needed, and
      there is no requirement on the reversibility of the path.

PMID- 16438606
TI  - Two-component desorption from anisotropic pore networks.
AB  - Dynamic Monte Carlo simulations are performed to explore molecular desorption of
      a two-component mixture from a mode adsorbent of adsorbate-related anisotropy.
      The intrinsic dynamics of the adsorbent-adsorbate host-guest system is described
      by assuming a situation typical of a "molecular-traffic-control" system, where
      the hopping rates of the two components in two directions, perpendicular to each
      other, are identical, while for each component, perpendicular to that direction
      of preferential propagation, the hopping rates are reduced. The resulting
      desorption patterns are discussed in terms of the jump probabilities and are
      shown to approach the corresponding analytical solutions in the limiting cases of
      isotropic and unidirectional diffusions.

PMID- 16438607
TI  - Polymer translocation through a nanopore: a two-dimensional Monte Carlo study.
AB  - We investigate the problem of polymer translocation through a nanopore in the
      absence of an external driving force. To this end, we use the two-dimensional
      fluctuating bond model with single-segment Monte Carlo moves. To overcome the
      entropic barrier without artificial restrictions, we consider a polymer which is
      initially placed in the middle of the pore and study the escape time tau required
      for the polymer to completely exit the pore on either end. We find numerically
      that tau scales with the chain length N as tau approximately N(1+2nu), where nu
      is the Flory exponent. This is the same scaling as predicted for the
      translocation time of a polymer which passes through the nanopore in one
      direction only. We examine the interplay between the pore length L and the radius
      of gyration R(g). For L<<R(g), we numerically verify that asymptotically tau
      approximately N(1+2nu). For L>>R(g), we find tau approximately N. In addition, we
      numerically find the scaling function describing crossover between short and long
      pores. We also show that tau has a minimum as a function of L for longer chains
      when the radius of gyration along the pore direction R( parallel) approximately
      L. Finally, we demonstrate that the stiffness of the polymer does not change the
      scaling behavior of translocation dynamics for single-segment dynamics.

PMID- 16438608
TI  - Coupling between lysozyme and trehalose dynamics: microscopic insights from
      molecular-dynamics simulations.
AB  - We have carried out molecular-dynamics simulations on fully flexible all-atom
      models of the protein lysozyme immersed in trehalose, an effective
      biopreservative, with the purpose of exploring the nature and extent of the
      dynamical coupling between them. Our study shows a strong coupling over a wide
      range of temperatures. We found that the onset of anharmonic behavior was
      dictated by changes in the dynamics and relaxation processes in the trehalose
      glass. The physical origin of protein-trehalose coupling was traced to the
      hydrogen bonds formed at the interface between the protein and the solvent.
      Moreover, protein-solvent hydrogen bonding was found to control the structural
      relaxation of the protein. The dynamics of the protein was found to be
      heterogeneous; the motions of surface and core atoms had different dependencies
      on temperature and, in addition, the surface atoms were more sensitive to the
      dynamics of the solvent than the core atoms. From the solvent perspective we
      found that the dynamics near the protein surface showed an unexpected enhanced
      mobility compared to the bulk. These results shed some light on the microscopic
      origins of the dynamical coupling in protein-solvent systems.

PMID- 16438609
TI  - Is Poisson-Boltzmann theory insufficient for protein folding simulations?
AB  - The Poisson-Boltzmann theory has been widely used in the studies of energetics
      and conformations of biological macromolecules. Recently, introduction of the
      efficient generalized Born approximation has greatly extended its applicability
      to areas such as protein folding simulations where highly efficient computation
      is crucial. However, limitations have been found in the folding simulations of a
      well-studied beta hairpin with several generalized Born implementations and
      different force fields. These studies have raised the question whether the
      underlining Poisson-Boltzmann theory, on which the generalized Born model is
      calibrated, is adequate in the treatment of polar interactions for the
      challenging protein folding simulations. To address the question whether the
      Poisson-Boltzmann theory in the current formalism might be insufficient, we
      directly tested our efficient numerical Poisson-Boltzmann implementation in the
      beta-hairpin folding simulation. Good agreement between simulation and experiment
      was found for the beta-hairpin equilibrium structures when the numerical Poisson
      Boltzmann solvent and a recently improved generalized Born solvent were used. In
      addition simulated thermodynamic properties also agree well with experiment in
      both solvents. Finally, an overall agreement on the beta-hairpin folding
      mechanism was found between the current and previous studies. Thus, our
      simulations indicate that previously observed limitations are most likely due to
      imperfect calibration in previous generalized Born models but not due to the
      limitation of the Poisson-Boltzmann theory.

PMID- 16438610
TI  - Finite-size scaling analysis on the phase transition of a ferromagnetic polymer
      chain model.
AB  - The finite-size scaling analysis method is applied to study the phase transition
      of a self-avoiding walking polymer chain with spatial nearest-neighbor
      ferromagnetic Ising interaction on the simple cubic lattice. Assuming the scaling
      M2(T,n) = n(-2beta/nu)[phi0 + phi1n(1/nu)(T-T(c)) + O(n(2/nu)(T-T(c))2)] with the
      square magnetization M2 as the order parameter and the chain length n as the
      size, we estimate the second-order phase-transition temperature T(c) = 1.784
      J/k(B) and critical exponents 2beta/nu approximately 0.668 and nu approximately
      1.0. The self-diffusion constant and the chain dimensions (R2) and (S2) do not
      obey such a scaling law.

PMID- 16438611
TI  - Computer simulations of diffusion and dynamics of short-chain polyelectrolytes.
AB  - Brownian dynamics simulations are conducted to investigate the diffusional and
      dynamic properties of polyelectrolytes in dilute salt-free solutions. The
      polyelectrolyte molecule is represented by a bead-spring chain in a primitive
      model. The long-range hydrodynamic and Coulomb interactions are both taken into
      consideration through the Ewald summations for the first time. The major finding
      of our simulations is that the dependence of the long-time chain diffusivity on
      the Coulomb interaction strength is very different from that of the Kirkwood
      short-time diffusivity, which simply shows a trend nearly opposite to the chain
      size. When ignoring the hydrodynamic interaction (HI), the coupling effect
      between the chain and its counterions gives rise to a noticeable increase in the
      long-time diffusivity at intermediate electrostatic interaction strengths.
      However, the incorporation of HI suppresses this effect to a degree that one can
      no longer discern it. Moreover, the rotational relaxation is found to show a
      dependence opposite to that of the gyration radius relaxation.

PMID- 16438612
TI  - Transient gratings generated by particulate suspensions: the uniformly irradiated
      sphere and the point source.
AB  - Expressions for the time dependence of the state variables in a transient grating
      experiment carried out on suspensions of particles can be determined by
      integration over space of the solutions for the temperature and photoacoustic
      pressure for a single particle. The method relies on independent computation of
      the thermal and acoustic modes of wave motion which are combined to give the
      temperature, pressure, and density in the grating as a function of time.
      Calculations are given for the uniformly irradiated droplet and the point source,
      the latter including the effects of a temperature-dependent thermal expansion
      coefficient. Transient grating experiments are reported in colloidal Pt that show
      features described in the calculation.

PMID- 16438613
TI  - Unbinding and preunbinding in surfactant solutions.
AB  - We propose models for the first-order unbinding transition of lyotropic lamellae
      in surfactant solutions. The coupling between the surfactant volume fraction and
      the elastic degree of freedom is considered so that the net attractive
      interaction between the surfactant molecules is enhanced. The elastic degree of
      freedom can be either (i) a membrane elastic degree of freedom or (ii) a bulk
      elastic degree of freedom. The phase behaviors of these two models are analyzed.
      For both cases, the unbinding transition becomes first order when the coupling is
      strong enough. We determine the associated preunbinding line which separates two
      lamellar phases having different repeat distances.

PMID- 16438614
TI  - Absorption spectra of liquid water and aqueous buffers between 0.3 and 3.72 THz.
AB  - We have developed a terahertz absorption spectrometer suitable for strongly
      absorbing liquids such as water, and have precisely measured the absorption
      spectrum of water between 0.3 and 3.72 THz (10-124 cm(-1)). We have also examined
      the absorption spectra of aqueous 50 mM potassium phosphate buffers at pH 3 and
      8, and find that they do not differ significantly from pure distilled de-ionized
      water.

PMID- 16438615
TI  - Complementarity and clustering in a simple model mixed bilayer.
AB  - A bilayer of uniform thickness containing a mixture of long and short lipids is
      simulated using a parallel hard-rod model to illustrate the effect of
      transbilayer repulsions between the tails of the long component. Monte Carlo
      simulations show considerable entropy-driven clustering within each layer.
      Demixing reaches a maximum at the highest packing fraction of the liquid state
      and decreases as the system orders. The formation of complementary clusters of
      long and short rods on opposite sides of the bilayer increases translational
      freedom within each cluster by reducing constraints imposed by the opposing
      leaflet, an effect that becomes less important as rods lock into facing
      hexagonally ordered arrays.

PMID- 16438616
TI  - Homogenization of boundary conditions for surfaces with regular arrays of traps.

PMID- 16438618
TI  - Photostability of bacteriochlorophyll a and derivatives: potential sensitizers
      for photodynamic tumor therapy.
AB  - The photostabilities of bacteriochlorophyll a and several of its derivatives,
      which are of interest as potential sensitizers in photodynamic tumor therapy,
      were investigated. The pigments were irradiated with light >630 nm in organic
      solvents (acetone, tetrahydrofuran, pyridine, methanol, ethanol, n-propanol, 2
      propanol and toluene) and in aqueous detergent solutions (cetyl-trimethyl
      ammonium bromide [CTAB], lauryldimethyl-aminoxide [LDAO] or sodium dodecyl
      sulfate [SDS] and Triton X-100 [TX100]). Their stabilities in these different
      solvents were determined in the presence and absence of an external sensitizer
      (pyromethyl-pheophorbide a), oxygen, sodium ascorbate and inert gas (Ar) or
      vacuum. The photodegradation products of bacteriochlorophyll a in acetone
      solution were isolated, purified by HPLC and analyzed by their absorption spectra
      and mass spectroscopy. Besides the well-known dehydrogenation products, such as
      [3-acetyl]-chlorophyll a, which were obtained as by-products, the major products
      had low absorption in the visible-near infrared spectral range. The spectral
      signature of the major component of these products was characteristic of linear
      open-chain tetrapyrroles, but they lacked the characteristic protonation
      deprotonation behavior and reactivity of bilins with Zn(++).

PMID- 16438620
TI  - Role of Helicobacter pylori in gastric cancer following partial gastrectomy for
      benign ulcer.

PMID- 16438619
TI  - Lipid rafts mediate ultraviolet light-induced Fas aggregation in M624 melanoma
      cells.
AB  - Ultraviolet light (UV) induces aggregation of Fas-receptor through a Fas-ligand
      independent pathway. However, the mechanism of ultraviolet light-induced Fas
      receptor aggregation is not known. In this report, we show that lipid rafts
      mediate ultraviolet light-induced aggregation of Fas. Our data show that UV
      induces a redistribution of Fas-receptor in a 25-5% Optiprep continuous gradient.
      The amount of Fas-receptorS is significantly increased in a gradient fraction
      that contain lipid rafts and is associated with an increase of FADD and caspase
      8. Our data also show that the active dimeric form of caspase-8 (p44/p41) is
      increased in the lipid raft fraction. In addition, our data show that
      cholesterol, a major component of lipid rafts, is significantly reduced in only
      the lipid raft fractions after UV-irradiation. However, ceramide, another major
      lipid raft component, is increased evenly in all gradient fractions after UV
      irradiation. These results suggest that UV alters the composition of major lipid
      raft components, which leads to the recruitment of Fas-receptor and FADD, with
      subsequent activation of caspase-8. Based on our results, we propose a novel
      mechanism by which UV induces apoptosis through a membrane lipid raft-mediated
      signaling pathway.

PMID- 16438621
TI  - Role of Helicobacter pylori in stomach cancer after partial gastrectomy for
      benign ulcer disease.
AB  - OBJECTIVE: To determine the prevalence of Helicobacter pylori infection in
      patients having undergone gastrectomy for non-neoplastic disease who later
      developed gastric stump cancer. MATERIAL AND METHODS: Retrospective study of all
      patients with partial gastrectomy for non-malignant peptic disease who were
      submitted to an endoscopic exploration between 1995 and 2001. A comparison was
      made of major clinical and histological characteristics, and the presence of
      Helicobacter pylori among patients with and without gastric cancer in the stomach
      remnant. RESULTS: A total of 73 patients were studied in this period. Fifteen
      patients (20.5%) had remnant-stump gastric cancer. All but one were
      adenocarcinomas (71% intestinal and 29% diffuse, respectively). The average time
      between diagnosis of gastric cancer and previous gastrectomy was 32 (14-48)
      years. There was a higher detection rate of Helicobacter pylori in patients with
      cancer in the gastric remnant (100 vs. 81.5%, respectively, p < 0.07). No
      relationship was seen between type of gastric reconstruction (Billroth I or II)
      and rate of Helicobacter pylori detection. CONCLUSIONS: Helicobacter pylori
      infection is frequent in patients with previous gastrectomy for non-neoplastic
      disease. The results of the study suggest that Helicobacter pylori infection may
      play a role in gastric stump cancer.

PMID- 16438622
TI  - Liver resection in metastatic colorectal cancer: a multidisciplinary approach.
AB  - AIM: To analyze qualitative short-time results of a new program for
      multidisciplinary liver evaluation in complex cases of liver metastasis from
      colorectal cancer. PATIENTS AND METHODS: 40 clinical consecutive evaluations with
      liver metastasis assessed for major liver resection by a multidisciplinary
      specialist committee. Complementary explorations performed included CT and
      ultrasounds, and MRI or PET for doubtful cases. Liver resection was made in a
      single operation or two-stage hepatectomy, or combined with other techniques.
      RESULTS: Postoperative mortality at 30 days was 4%. Complications occurred in
      28%, with surgical wound infection being most frequent (20%); 16.6% of resections
      were transfused, with a mean volume of 1000 ml. Two patients needed reoperation 
      one for an intraperitoneal abscess and one for bile-duct stenosis. Percentage of
      global relapse was 36%, with 26% of relapses out of the liver. Actuarial survival
      at one year follow-up was 90%, and 82% at two years; 64% of patients remain free
      of disease two years after the operation. CONCLUSIONS: Programs for liver
      resection for colorectal cancer metastasis may be implemented by
      multidisciplinary teams of recent setup. There is a need to evaluate own results
      and then compare them with a standard of quality previously reported.

PMID- 16438623
TI  - Perceived health status in celiac disease.
AB  - INTRODUCTION: Chronic conditions modify perceived health in affected individuals.
      For this reason celiac disease, being a chronic condition, may impair health
      related quality of life (HRQOL). OBJECTIVE: To analyze the impact of celiac
      disease in affected individuals. METHOD: Observational, cross-sectional,
      prospective study in patients with celiac disease by administering two HRQOL
      questionnaires: EuroQol-5D and GastroIntestinal Quality of Life (GIQLI). RESULTS:
      54 stable patients on a gluten-free diet for a median 60 months, and 9 newly
      diagnosed individuals still on their usual diet were included. Overall GIQLI
      score was significantly higher, meaning a better HRQOL, in treated celiac
      patients versus pre-treated celiac patients (3.1 [2.7-3.5] vs. 2.4 [2.1-2.6], p <
      0.01). Similarly, EuroQol s health status preference value was also significantly
      better in treated patients (0.87[0.8-1.0] vs. 0.7 [0.5-0.8], p < 0.01). EuroQol s
      visual analogic scale had also better scores, representing a better perceived
      health, among treated patients (80.0 [70.0-90.0] vs. 65.0 [40.0-71.0], p < 0.05).
      In comparison to EuroQol-5D scores among the healthy Spanish population, values
      obtained for celiac patients under treatment are similar to those seen in the
      general population. CONCLUSIONS: celiac disease impairs perceived health in
      affected individuals, which improves and reaches results similar to those in the
      general population when on a gluten-free diet.

PMID- 16438624
TI  - Role of intestinal bacterial overgrowth and intestinal motility in bacterial
      translocation in experimental cirrhosis.
AB  - BACKGROUND: Intestinal bacterial overgrowth (IBO) is related to small bowel
      motility and has been involved in the pathogenesis of bacterial translocation
      (BT) in experimental models, and both overgrowing gut flora and translocating
      bacteria to mesenteric lymph nodes are common features in cirrhosis. OBJECTIVES:
      The aims of this study were to analyze cecal aerobic bacteria and intestinal
      transit in cirrhotic rats, and their relationship with BT, evaluating the role of
      intestinal bacterial overgrowth and small bowel dismotility in the development of
      BT in experimental cirrhosis. MATERIAL AND METHODS: We included twenty-seven male
      Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis without ascites
      and ten controls. Cultures of mesenteric lymph nodes (MLN), peripheral and portal
      blood, liver, spleen and cecal samples were carried out. Small intestinal transit
      was determined in ten cirrhotic rats and in ten control rats. RESULTS: The
      prevalence of bacterial translocation was 56%. Total cecal aerobic bacteria count
      was significantly higher in cirrhotic rats than in control rats (p < 0.001).
      Cirrhotic rats with translocated bacteria had higher total aerobic intestinal
      counts than culture-negative MLN bacteria (p < 0.05). The prevalence of total
      intestinal bacterial overgrowth in cirrhotic animals was 67%, and 0% in control
      animals (p < 0.001). According to BT, total IBO was more frequent in cirrhotic
      rats with BT versus those without BT (93 vs. 33%) (p < 0.001). Of the
      translocating bacteria, 95.6% were found to be overgrown in the cecum. The small
      intestinal transit was slower in cirrhotic rats (60.5 +/- 12.7 cm vs. 81.2 +/-
      5.7 cm) than in control animals (p < 0.001). CONCLUSIONS: These results suggest
      that the increase of intestinal aerobic bacteria in experimental cirrhosis is
      associated with translocation. In addition, IBO is frequent in cirrhotic rats,
      and is supposed to play an important role in the development of BT. Impaired
      motility of the small intestine is a common feature in cirrhosis and may be
      implicated in the pathogenesis of IBO.

PMID- 16438625
TI  - Bone metabolism changes in patients with inflammatory bowel disease.

PMID- 16438626
TI  - Refractory hepatic hydrothorax: successful treatment with octreotide.
AB  - We report the case of a patient that developed hepatic hydrothorax as the first
      complication of liver cirrhosis. Due to the lack of response to diuretics,
      pleurodesis and TIPS, treatment with octreotide was started with resolution of
      hydrothorax. To the best of our knowledge, this is the third reported case of
      refractory hepatic hydrothorax with complete and sustained response to
      octreotide.

PMID- 16438627
TI  - Pancreatic intraductal papillary mucinous tumor.

PMID- 16438628
TI  - [Anal prolapse of a sigmoid lipoma: report of a case].

PMID- 16438629
TI  - [Methyldopa-induced acute toxic hepatitis].

PMID- 16438630
TI  - [Yeyunal intussusception secondary to a multiple IgG myeloma].

PMID- 16438631
TI  - [CA 19.9 and pulmonary fibrosis].

PMID- 16438633
TI  - [Zenker's diverticulum: diagnosis by plain radiographic examination].

PMID- 16438632
TI  - [Atipic manifestation of an infrequent lesion. Video- and ecoendoscopy in a
      gastric schwannoma].

PMID- 16438634
TI  - [Anaphylactic shock in a patient with hydatidic cyst].

PMID- 16438635
TI  - [Complicated retroperitoneal hematoma. Report of two cases].

PMID- 16438636
TI  - Building service capacity within a regional district mental health service:
      recommendations from an Indigenous mental health symposium.
AB  - CONTEXT: In response to recent developments within the mental health services of
      south-east Queensland, the Toowoomba District Mental Health Service (TDMHS) has
      developed a Model of Service Delivery, which outlines the range of services
      provided for consumers across their lifespan. Indigenous consumers of the TDMHS
      come from a wide area of communities in the surrounding shires (Rural, remote and
      metropolitan areas (RRMA) 4-7). It was recognised by the service that Indigenous
      mental health consumers have unique needs and, because of these needs, this area
      of service delivery required greater attention and further development. In
      December 2004, a symposium was organised by the service to bring together a range
      of speakers and delegates working in the area of Indigenous mental health to
      discuss issues and work towards developing strategies to enable the service to
      better meet the needs of Indigenous consumers in this region of south-east
      Queensland. ISSUES: The symposium program consisted of keynote speakers and
      invited papers and culminated with an afternoon workshop that collated the
      symposium's main issues and themes around building service capacity for
      Indigenous mental health consumers. The objective of the workshop was
      'Identifying ways to meet Indigenous mental health needs'. This workshop gave the
      delegates a chance to reflect, discuss and brainstorm the major issues of concern
      relating to this question. A group facilitator guided the discussion and
      organised the delegates into groups to evaluate, debate and propose
      recommendations for each of the major issues that emerged. LESSONS LEARNED: The
      feedback and discussion arising from the workshop is presented. Sixteen major
      themes emerged from the workshop. Seven of these were voted by the participants
      as being dominant and in greatest need of discussion: (1) communication; (2)
      cultural respect; (3) culturally appropriate clinical tools; (4) supportive
      management; (5) patient compliance; (6) career structure; and (7) empowerment.
      These seven themes are discussed and recommendations arising from the workshop
      are noted.

PMID- 16438637
TI  - Communication with patient, family and community in the rural world.
AB  - The rural world and its population have their own characteristics, different from
      the urban world, which contribute to creating a unique framework for physician
      patient communication and relationship. On most occasions the physician arrives
      in the village from some other setting and must adapt. He or she must make a good
      first impression on the neighbours, and learn the language they use to describe
      the most common illnesses and symptoms (sickness, indigestion, faintness, lack of
      appetite...), because the doctor must use the patients' language. Moreover, the
      doctor has to accept being permanently observed and identified. Thus, this
      Spanish personal view takes the reader into the world of the rural doctor.

PMID- 16438638
TI  - Guiding principles for successful innovation in regional medical education
      development.
AB  - This is an era of extraordinary expansion in medical education in both the
      developed and developing world. This article reflects on the author's experience
      in implementing new regional medical education programs, and distils ten
      principles to guide successful innovation once funding for such development has
      been achieved.

PMID- 16438639
TI  - Identification of two HIV type 1 circulating recombinant forms in Brazil.
AB  - Recombination is an important way to generate genetic diversity. Accumulation of
      HIV-1 full-length genomes in databases demonstrated that recombination is
      pervasive in viral strains collected globally. Recombinant forms achieving
      epidemiological relevance are termed circulating recombinant forms (CRFs).
      CRF12_BF was up to now the only CRF described in South America. The objective was
      to identify the first CRF in Brazil conducting full genome analysis of samples
      sharing the same partial genome recombinant structure. Ten samples obtained from
      individuals residing in Santos, Brazil, sharing the same recombination pattern
      based on partial genome sequence data, were selected from a larger group to
      undergo full length genome analysis. Near full length genomes were assembled from
      overlapping fragments. Mosaic genomes were evaluated by Bootscan, alignment
      inspection, and phylogenetic analysis using neighbor joining and maximum
      likelihood. Full genomes were also analyzed by split decomposition. We were able
      to identify five mosaic genomes. Two of these structures were represented by at
      least three samples derived from epidemiologically unlinked individuals. These
      structures were named CRF28_BF and CRF29_BF and are the second and third CRFs
      composed exclusively by subtypes B and F as well as the second and third CRFs
      encountered in South America. Other recombinant forms studied here resembled
      CRF28_BF and CRF29_BF. Our results suggest that a diverse population of related
      recombinants, including CRFs may play an important part in the Brazilian and
      South American epidemic.

PMID- 16438640
TI  - Serum albumin as a prognostic indicator for HIV disease progression.
AB  - Low albumin levels have been associated with HIV progression. The objective of
      this analysis was to confirm this association and to further examine the effect
      of albumin before and after HIV seroconversion on disease progression. The
      association was first examined among individuals already infected with HIV at
      entry into a community-based cohort (n = 453) and further assessed among HIV
      seroconverters with albumin concentrations measured after (n = 219) and before
      seroconversion (n = 138). The prognostic effect of albumin on AIDS, AIDS
      mortality, and all-cause mortality was examined using Cox regression. Among 453
      HIV-infected individuals, albumin <35 g/liter was associated with faster
      progression to AIDS [adjusted relative hazard (ARH), 1.8; 95% confidence interval
      (CI), 1.2-2.8], AIDS mortality (ARH, 2.2; 95% CI, 1.3-3.8), and all-cause
      mortality (ARH, 2.4; 95% CI, 1.6-3.5). Analyses restricted to HIV seroconverters
      were similar. Preseroconversion levels of albumin did not predict outcomes, but
      HIV seroconversion appeared to lower albumin levels. These data show that albumin
      <35 g/liter after HIV seroconversion is associated with faster HIV disease
      progression and suggest that low albumin levels are probably a consequence of HIV
      infection rather than merely reflective of some individuals inherently having low
      albumin levels.

PMID- 16438641
TI  - Genotypic and phenotypic analyses of human immunodeficiency virus type 1 in
      antiretroviral drug-naive Nigerian patients.
AB  - We analyzed the subtypes and genotypic and phenotypic drug susceptibility
      profiles of 18 HIV-1 isolates from treatment-naive patients in Nigeria. A
      modified gp41-based heteroduplex mobility assay was used to determine the clade
      designation based on the envelope gene. The protease and most of the reverse
      transcriptase regions were cloned into a retroviral expression vector and
      sequenced. Samples were also analyzed phenotypically using a rapid phenotypic
      assay (PhenoSense HIV, ViroLogic, Inc.). According to the modified gp41-based
      heteroduplex mobility assay, the patients were infected with either clade G (17
      specimens) or clade A (one specimen) isolates. From phylogenetic analyses of 1212
      nucleotides of the polymerase gene, 14 of the 18 isolates were strongly grouped
      with subtype G reference strains. The remaining four isolates were grouped with
      the CRF_02_AG clade. Within the protease region, all 18 isolates had
      mutations/polymorphic substitutions at six locations compared to the HIV-1 NL4-3
      reference sequence, two of which have been associated with resistance to protease
      inhibitors (K20I and M36I). At least half of the isolates had
      mutations/polymorphic substitutions at an additional five positions in the
      protease region. Within the reverse transcriptase (RT) region, all 18 isolates
      showed an E291D mutation/polymorphic substitution. Mutations/polymorphic
      substitutions were also found in at least half of the isolates at 21 positions.
      The phenotypic profiles of the viruses correlated well with the observed
      genotypes. Two isolates showed slightly reduced susceptibility to one or two of
      the five PIs assessed (ritonavir and ritonavir/nelfinavir) and all 18 viruses
      were susceptible to all NRTIs and NNRTIs analyzed.

PMID- 16438642
TI  - Short communication: characteristics of effective immune control of simian/human
      immunodeficiency virus in pigtail macaques.
AB  - Considerable evidence suggests both HIV-specific T cells and neutralizing
      antibodies (nAb) can, separately, assist control of viremia. T cell and nAb
      responses were studied in detail in three pigtail macaques protected from chronic
      simian/human immunodeficiency virus (SHIV) viremia by DNA prime/fowlpoxvirus
      boost vaccine regimens. Immunity was studied both after an initial intrarectal
      SHIV challenge, as well as during CD8 T cell depletion and a subsequent
      intravenous SHIV rechallenge. Remarkably, SHIV-specific CD4 and CD8 T cells were
      detectable in the absence of viremia following an initial SHIV challenge in one
      animal, subsequent to recovery from CD8 T cell depletion in all three animals,
      and following control of heterologous SHIV rechallenge in two animals.
      Neutralizing antibodies were also enhanced following CD8 depletion without
      recrudescence of viremia in all three animals. These observations, although in a
      small subset of animals, suggest the hypothesis that combinations of primed T
      cell immunity and neutralizing antibodies can maintain control of chronic primate
      lentiviral infections.

PMID- 16438644
TI  - Sustained HIV viral suppression following treatment interruption: an
      observational study.
AB  - Treatment of HIV-infected patients with HAART can result in long-term suppression
      of viral loads to undetectable levels. Rapid virologic rebound typically follows
      treatment interruption (TI), with a potential for significant loss of CD4+ cells.
      Patients who maintain virologic suppression despite interrupting treatment have
      not been well described. All patients with a pretreatment viral load (VL) > or =
      5000 copies/ml, who had been on therapy for > or = 2 weeks, and who underwent a
      TI lasting > or = 180 days were analyzed. Patients whose maximum VL did not
      exceed 5000 copies/ml > or = 6 months after starting TI ("nonrebounders") were
      compared with those whose VL exceeded 5000 copies/ml (rebounders). Seventy-one
      patients were included in the analysis. Nineteen (27%) were nonrebounders. Ninety
      four percent of patients in each group interrupted treatment for reasons
      unrelated to virologic response. Median change in CD4 count during TI was not
      significantly different between the nonrebounder and rebounder groups (
      20.5/microl vs. -64.0/microl; p < 0.086). In a multivariate logistic regression
      analysis, the following factors predicted nonrebounder status: peak VL before TI
      (log10 copies/ml) (OR = 0.14, 95% CI = 0.04-0.48, p = 0.0016); having received
      HAART (vs. mono/dual therapy) as initial regimen (OR: 11.0, 95% CI: 2.04-59.8, p
      = 0.0054); and female gender (OR = 4.8, 95% CI = 1.09-21.5, p = 0.0384). The
      large majority of chronically infected HIV patients with a TI > or = 180 days
      interrupted treatment for reasons unrelated to virologic response. Almost 30% did
      not have a significant virologic rebound. Those patients were more likely to be
      female, had a lower peak VL prior to treatment, and their initial regimen was
      more likely to be HAART. Examining the immune responses of nonrebounders may
      contribute to the understanding of protective immunity to HIV.

PMID- 16438643
TI  - Longitudinal study on mitochondrial effects of didanosine-tenofovir combination.
AB  - Tenofovir disoproxil fumarate (TDF) has been reported to be free of adverse
      effects on mitochondria. We evaluate the effects of the introduction of TDF in a
      didanosine (ddI)-based highly active antiretroviral therapy (HAART) on
      mitochondrial DNA (mtDNA) content, mitochondrial mass (MM), and cytochrome c
      oxidase (COX) activity of the oxidative phosphorylation (OXPHOS) system over a 12
      month period. Forty-four asymptomatic HIV patients with undetectable viral load
      receiving a ddI-based HAART were recruited and switched to ddI plus TDF (ddI +
      TDF) and nevirapine (n = 22) or maintained with the same baseline ddIbased HAART
      scheme (n = 22). Peripheral blood mononuclear cells were obtained at 0, 6, and 12
      months. COX activity and MM were determined by spectrophotometry and the mtDNA
      content by quantitative realtime PCR. The mtDNA content showed a progressive
      decrease over the 12-month period of the study for the two groups with respect to
      baseline, with such a decrease statistically significant only in the ddI + TDF
      group (55% decrease, p < 0.001). In addition, the decrease of mtDNA content over
      time was statistically different between both groups (p < 0.001). Consistently,
      MM and COX activity decreased significantly at 12 months with respect to baseline
      only in the ddI < TDF group (28% decrease for MM, p < 0.05; 47% decrease for COX
      activity, p < 0.001). We conclude that switching to a HAART regimen containing
      ddI + TDF is associated with evolutive mitochondrial damage expressed as mtDNA
      depletion, loss of MM, and decrease in COX efficiency. The particular relevance
      of either ddI, TDF, or any interaction between them in such a mitochondrial
      dysfunction remains to be established.

PMID- 16438645
TI  - Mycobacterium tuberculosis upregulates coreceptors CCR5 and CXCR4 while HIV
      modulates CD14 favoring concurrent infection.
AB  - Tuberculosis is the most frequent coinfection in humans infected with HIV-1, but
      little is known about mechanisms that favors coinfection. The aim of this work is
      to understand tuberculosis and HIV infections. We determined the pattern of
      expression of CD11c, CD14, CD40, CCR5, and CXCR4 and quantified IL-1beta, IL-6,
      IL-8, TNF-alpha, and RANTES in tuberculosis patients and HIV patients. Monocytes
      from healthy PPD+ volunteers (HP(+)V) stimulated with intracellular proteins
      (IP), lipids, and polysaccharides (PLS) from Mycobacterium tuberculosis down
      regulate CD11c expression (p < 0.05). On the contrary, CD14 expression was
      elevated in tuberculosis patients (p < 0.05) and HIV-infected patients (p >
      0.05). CD14 expression was elevated on monocytes from HP(+)V stimulated with PLS
      and lipids (p < 0.05). CD40 low expression was found in tuberculosis patients and
      on monocytes from HP(+)V stimulated with lipids, but it was elevated in HIV
      infected patients (p < 0.05). CXCR4 and CCR5 expression was high in pulmonary
      tuberculosis patients and low in HIV-infected patients (p < 0.05). Finally, CCR5+
      monocytes from HP(+)V after stimulation with PLS and CXCR4+ lymphocytes were
      elevated after stimulation with IP (p < 0.05). In general, high levels of IL
      1beta, IL-6, and TNF-alpha were found in all groups, but low levels of RANTES
      were found in pulmonary tuberculosis patients. In conclusion, the pulmonary
      tuberculosis patients have a microenvironment that facilitates the HIV infection
      through three possible mechanisms: (1) increasing the coreceptor for HIV
      entrance, (2) increasing proinflammatory cytokines, and (3) down-regulating
      RANTES. At the same time, HIV patients have a microenvironment that facilitates
      entry of M. tuberculosis into macrophages through CD14.

PMID- 16438647
TI  - Selection and characterization of a replication-competent human immunodeficiency
      virus type 1 variant encoding C-terminally truncated env.
AB  - A long cytoplasmic C-terminus (Env-CT) on the human immunodeficiency virus type 1
      (HIV-1) Env protein is a highly conserved feature in vivo. Mutant HIV lacking the
      Env-CT cannot replicate in PBMCs and in the majority of T cell lines
      (nonpermissive cells, e.g., H9 cells) in vitro. We report here that a single
      amino acid change (N750K) in the context of the mutant virus pNL-Tr752 lacking
      104 C-terminal Env amino acids gives rise to a virus variant pNL-Tr752(N750K),
      which can now replicate in nonpermissive H9 cells and, albeit to a lower extent,
      in PBMCs. We have analyzed the properties of replication-competent pNL
      Tr752(N750K) in comparison to its defective counterpart pNL-Tr752 and to wild
      type virus in H9 cells. In all cases, the respective glycoproteins were
      functional in inducing membrane fusion and were incorporated into particles. In
      comparison to pNL-Tr752 and pNL-Wt, pNL-Tr752(N750K) glycoprotein exhibited
      increased fusion induction and 2- to 3-fold increased incorporation into
      particles, properties that may contribute to the observed replication competence.

PMID- 16438646
TI  - Detection of T lymphocytes specific for human endogenous retrovirus K (HERV-K) in
      patients with seminoma.
AB  - Human endogenous retrovirus K (HERV-K) is distinctive among the retroviruses that
      comprise about 8% of the human genome in that multiple HERV-K proviruses encode
      full-length viral proteins, and many HERV-K proviruses formed during recent human
      evolution. HERV-K gag proteins are found in the cytoplasm of primary tumor cells
      of patients with seminoma. We identified HERV-K-specific T cells in patients with
      a past history of seminoma using the interferon-gamma ELISPOT assay and an MHC
      HERV-K peptide-specific tetramer. A minority of apparently healthy subjects
      without evident germ cell tumors also made HERV-K-specific T cell responses. In
      summary, we detected T cell reactivity to HERV-K peptides in both past seminoma
      patients and a minority of apparently healthy controls.

PMID- 16438648
TI  - HIV type 1 persistence in CD4- /CD8- double negative T cells from patients on
      antiretroviral therapy.
AB  - The establishment of reservoirs of latently infected cells is thought to
      contribute to the persistence of HIV-1 infection in the host. Studies so far have
      mainly focused on the long-lived reservoir of HIV-infected resting CD4+ T cells.
      A discrete population of HIV-infected CD4-/CD8- double negative (DN) T cells has
      recently been shown to exist and may also play a role in HIV-1 persistence. DN T
      cells are CD3 positive, either TCRalphabeta or TCRgammadelta positive, but lack
      both CD4 and CD8 surface markers. We developed a novel, magnetic bead column
      based cell fractionation procedure for isolating >99% pure DN T cells. CD4+,
      CD8+, and DN T cells were purified from 23 samples of a cohort of 18 HIV-1
      infected patients. Each cell fraction was analyzed for levels of total and
      integrated HIV-1 DNA. A correlation was observed between the presence of HIV-1
      DNA in the DN T cell fraction and plasma viral load (VL). Using a micrococulture
      technique, we saw an initial release of virus from DN T cells of a patient with
      high VL. Analysis of env and nef sequence data suggested that the HIV-1 present
      in CD4+ and DN T cells originated from a common infecting strain. Different from
      the published literature, we have demonstrated the presence of HIV-1 DNA in DN T
      cells only in patients who are experiencing HAART failure. While these cells may
      have a limited role in viral persistence in high VL patients, our results suggest
      DN T cells are unlikely to be a major reservoir in patients on HAART with
      clinically undetectable plasma viral RNA.

PMID- 16438649
TI  - The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the
      tat/rev Intron on HIV Type 1 Envelope Expression.
AB  - A complex mRNA splicing pattern, which remains to be fully characterized,
      influences HIV-1 gene expression. In this study, poor envelope expression of a
      primary HIV-1 isolate was observed and linked to increased splicing of the two
      coding exons of tat/rev. The substitution of a nucleotide G, located 28
      nucleotides upstream of the splice acceptor site SA7 in the recently identified
      intron splicing silencer sequence, was found to be responsible for the poor
      envelope expression. A single nucleotide substitution of G with A at this
      position results in a poor envelope expression phenotype. Moreover, substitution
      of the nucleotide G with any other nucleotide in an infectious HIV-1 proviral
      clone, HXB2RU3, results in poor envelope expression. The substitution of this
      nucleotide reduces the hnRNP A1 binding affinity but increases the splicing of
      env mRNA. The nucleotide G at this position is highly conserved among HIV-1
      isolates and appears to play a critical role in HIV-1 splicing.

PMID- 16438650
TI  - Identification of HIV type 1 group N infections in a husband and wife in
      Cameroon: viral genome sequences provide evidence for horizontal transmission.
AB  - HIV-1 is classified into three groups, M (major), N (non-M non-O), and O
      (outlier); each group arose from a separate transmission of SIVcpz into humans.
      HIV-1 group N was recently discovered and infections with this virus are rare
      with only eight documented cases. All group N infections have been found in
      Cameroon and there is no evidence of direct linkage between the infected
      patients. We report here the identification of HIV-1 group N infections in a
      husband and wife. The group N infection in the husband, 1131-03, was identified
      first based on seroreactivity in peptide EIAs and confirmed by PCR amplification
      of group N viral sequences. Subsequently the wife, 1015-04, was evaluated and
      confirmed to also be infected with a group N virus. Near full-length viral
      genomes were amplified and sequenced from each patient's specimen. The low level
      of diversity between the two viral sequences provides evidence of horizontal
      transmission of group N from one spouse to the other. Patient 1131-03 was
      receiving antiviral therapy consisting of reverse transcriptase inhibitors; the
      treatment appears effective for suppression of group N viral replication based on
      apparently low viral load in plasma specimens collected from the patient and the
      absence of drug resistance mutations in RT sequences amplified from 1131-03. This
      report brings to 10 the number of group N infections identified and to 5 the
      number of group N genomes sequenced. Although group N infections continue to be
      rare, group N is a pathogenic virus and its prevalence needs to be monitored.

PMID- 16438651
TI  - Activation of HIV type 1 specific cytotoxic T lymphocytes from semen by HIV type
      1 antigen-presenting dendritic cells and IL-12.
AB  - Seminal HIV-1-specific cytotoxic T lymphocytes (CTLs) could provide an important
      immune defense against local HIV-1 infection, and be important in impeding the
      spread of HIV-1 infection. In this study, we demonstrate that autologous blood
      derived dendritic cells (DCs) loaded in vitro with synthetic HIV-1 peptides
      representing known CTL epitopes activated HLA class I restricted, anti-HIV-1 CTLs
      and interferon gamma responses in seminal CD8+ T cells from subjects with chronic
      HIV-1 infection on antiretroviral therapy. CTLs specific for the same HLA
      restricted epitopes were detected in semen and blood of the same individuals by
      stimulation with peptide-loaded DCs. Anti-HIV-1 CTL responses from semen were
      enhanced by stimulation with DCs loaded with HIV-1 peptides and interleukin 12.
      Our results suggest that blood-derived DCs have HIV-1 antigen-presenting capacity
      for seminal CTL in HIV-1-infected subjects. The DC-T cell system can serve as a
      model for immunotherapy of HIV-1 infection in the local genital tract as well as
      systemic blood circulation.

PMID- 16438652
TI  - Elicitation of immunity to HIV type 1 Gag is determined by Gag structure.
AB  - The gag gene of the human immunodeficiency virus type 1 (HIV-1) encodes for viral
      proteins that self-assemble into viral particles. The primary Gag gene products
      (capsid, matrix, and nucleocapsid) elicit humoral and cellular immune responses
      during natural infection, and these proteins are included in many preclinical and
      clinical HIV/AIDS vaccines. However, the structure (particulate or soluble) of
      these proteins may influence the immunity elicited during vaccination. In this
      study, mice were inoculated with four different HIV-1 Gag vaccines to compare the
      elicitation of immune responses by the same Gag immunogen presented to the immune
      system in different forms. The immunity elicited by particles produced in vivo by
      DNA plasmid (pGag) was compared to these same proteins retained intracellularly
      (pGag(DMyr)). In addition, the elicitation of anti- Gag immunity by Gag(p55)
      virus-like particles (VLPs) or soluble, nonparticulate Gag(p55) proteins was
      compared. Enhanced cellular responses, but almost no anti-Gag antibodies, were
      elicited with intracellularly retained Gag proteins. In contrast, DNA vaccines
      expressing VLPs elicited both anti-Gag antibodies and cellular responses. Mice
      vaccinated with purified Gag(p55) VLPs elicited robust humoral and cellular
      immune responses, which were significantly higher than the immunity elicited by
      soluble, nonparticulate Gag(p55) protein. Overall, purified particles of Gag
      effectively elicited the broadest and highest titers of anti-Gag immunity. The
      structural form of Gag influences the elicited immune responses and should be
      considered in the design of HIV/AIDS vaccines.

PMID- 16438653
TI  - Genetic variability of gag and env regions of HIV type 1 strains circulating in
      Slovenia.
AB  - The aim of this study was to investigate the genetic diversity of HIV-1 strains
      circulating in Slovenia. Proviral DNA isolated from peripheral blood mononuclear
      cells (PBMCs) of 20 randomly selected HIV-1-infected individuals was classified
      into subtypes by sequence-based phylogenetic analysis of the env (C2V3) and gag
      (p24) regions of the viral genome. The phylogenetic tree based on env C2V3
      sequences showed that 15 of the 20 samples were subtype B, two A1, one F1, one
      CRF01_AE, and one CRF02_AG. The phylogenetic analysis of the gag gene yielded
      identical results expect for one sample that had a discordant subtype; it was
      identified as subtype A1 in the env and AE in the gag region. Our study confirmed
      that although subtype B predominates, other subtypes and circulating recombinant
      forms (CRFs) are also present in Slovenia. The high intrasubtype genetic
      diversity of subtype B sequences suggests a multiple introduction of subtype B
      strains into Slovenia.

PMID- 16438654
TI  - Evolution of SIV envelope in morphine-dependent rhesus macaques with rapid
      disease progression.
AB  - Three morphine-dependent rhesus macaques that developed accelerated AIDS after
      virus inoculation, along with three control macaques, were followed for evolution
      of the SIV/17E-Fr envelope. Viral RNA was isolated from plasma samples collected
      at weeks 6, 12, and 20 postinfection. A 482-nucleotide fragment in the viral env
      was amplified and cloned into a pCR2.1-TOPO vector. Between 5 and 10 clones were
      sequenced at each time point from individual monkeys. The sequence analysis
      showed more mutations in the control animals compared to those seen in the
      morphine-dependent animals. The virus at different points did not separate
      completely in phylogenetic analysis. However, the phylogenetic clustering was
      more apparent in the control animals. Viral diversity and divergence were
      significantly higher in the control animals. The control animals lost N
      glycosylation sites more rapidly. These results suggest that morphine dependence
      diminished virus evolution in SHIV/SIV-infected rhesus macaques and there was an
      inverse correlation between virus evolution and onset of clinical disease.

PMID- 16438656
TI  - An interview with Elaine Heron, Ph.D., CEO, and Richard Ellson, CTO, Labcyte Inc.
      Interview by Vicki Glaser.

PMID- 16438657
TI  - Multiparameter analysis of a screen for progesterone receptor ligands: comparing
      fluorescence lifetime and fluorescence polarization measurements.
AB  - Direct measurement of the fluorescence lifetime (FLT) of a fluorescent label is
      an emerging method for high-throughput screening. Changes in the fluorescence
      lifetime can be correlated to changes in the non-radiative relaxation pathway(s)
      for the excited state of the label. These pathways can be environmentally
      sensitive, such as when a labeled analyte is free in solution versus bound to a
      receptor. Because lifetime is an intrinsic property of a fluorophore, it is not
      concentration dependent, and therefore has advantages similar to those of
      ratiometric fluorescent techniques such as fluorescence resonance energy transfer
      or fluorescence polarization. We have applied the FLT measurement technique to a
      screen of a small compound library in order to identify compounds that bind to
      the progesterone receptor, and compared the results to those obtained by
      performing the assay in fluorescence polarization mode. Each readout modality
      showed excellent Z'; values, with the FLT readout performing slightly better in
      this respect. Interfering compounds could be rapidly identified for either assay
      format by comparing the results between the two formats.

PMID- 16438658
TI  - High content kinetic assays of neuronal signaling implemented on BD pathway HT.
AB  - A great deal of information can be gained from kinetic fluorescence-based
      measurement of cellular responses; however, until recently the use of such
      approaches has been limited by the manual nature of the instrumentation
      available. Higher-throughput kinetic studies of signaling pathways are greatly
      facilitated by new confocal, liquid handling-enabled, high content screening
      (HCS) platforms. In the present work, we have implemented one such instrument,
      the BD(TM) Pathway HT bioimager (BD Biosciences, Rockville, MD), for studying
      regulation of neuronal signaling pathways. We have established a neuronal calcium
      oscillation model, whereby rate of oscillation, amplitude of oscillation, and
      level of synchronicity across the culture can be measured. We have implemented
      membrane potential measurement using fluorescence resonance energy transfer-based
      dyes, for single cell characterization on this platform, showing the benefits of
      a truly flexible excitation and recording system; this dye combination cannot be
      readily implemented on all HCS platforms because of constraints of excitation
      wavelengths. We have validated long-term intracellular calcium imaging
      experiments, using innovative dyes and BD Pathway HT's spinning disk-based
      confocal excitation. To maximize both throughput and reproducibility, walk-away
      automation integration of this bioimaging technology has been implemented,
      producing an affordable, compact platform for fully automated kinetic HCS.

PMID- 16438659
TI  - The development of an europium-GTP assay to quantitate chemokine antagonist
      interactions for CXCR4 and CCR5.
AB  - Chemokine receptors have been implicated in several disease processes such as
      acute and chronic inflammation, cancer, and allograft rejection and are therefore
      targets for drug development. The chemokine receptors CCR5 and CXCR4 are of
      particular interest as they serve as entry cofactors for human immunodeficiency
      virus. These receptors are members of the G protein-coupled receptor (GPCR)
      family. In this respect, assessing GPCR activation by GTP binding is an important
      tool to study the early stage of signal transduction. The assay normally utilizes
      the non-hydrolysable GTP analogue guanosine 5'-gamma-[35S]thiotriphosphate. In
      order to avoid the problems involved in working with radioactivity, a new non
      radioactive version of the assay was developed using a europium-labeled GTP
      analogue in which europium-GTP binding can be assayed using time-resolved
      fluorescence. The assay was optimized for CXCR4 and CCR5 and validated for
      screening of chemokine antagonists using the small molecule CXCR4 antagonist
      AMD3100 and CCR5 antagonists.

PMID- 16438660
TI  - Development of homogeneous high-affinity agonist binding assays for 5-HT2
      receptor subtypes.
AB  - The serotonin (5-hydroxytryptamine) 5-HT2 receptor subfamily consists of three
      members, 5-HT2A, 5-HT2B, and 5-HT2C. These receptors share high homology in their
      amino acid sequence, have similar signaling pathways, and have been indicated to
      play important roles in feeding, anxiety, aggression, sexual behavior, mood, and
      pain. Subtype-selective agonists and antagonists have been explored as drugs for
      hypertension, Parkinson's disease, sleep disorders, anxiety, depression,
      schizophrenia, and obesity. In this study, we report the development of
      homogeneous agonist binding assays in a scintillation proximity assay (SPA)
      format to determine the high-affinity binding state of agonist compounds for the
      human 5-HT2C, 5-HT2A, and 5-HT2B receptors. The 5-HT2 agonist 1-(4- [125I]iodo
      2,5-dimethoxyphenyl)-2-aminopropane ([125I]DOI) was used to label the high
      affinity sites for the 5-HT2A and 5-HT2C receptors. The high-affinity sites for
      the 5-HT2B receptor were labeled with [3H]lysergic acid diethylamide. Total
      receptor expression was determined with the 5-HT2 antagonist [3H]mesulergine for
      the 5-HT2B and 5-HT2C receptors, and [3H]ketanserin for the 5-HT2A receptor. The
      agonist high-affinity binding sites accounted for 2.3% (5-HT(2C) receptor), 4.0%
      (5-HT2A receptor), and 22% (5-HT2B receptor) of the total receptor population.
      Competition binding studies using known agonists indicated high Z' values of the
      agonist binding assays in SPA format (Z' > 0.70). The Ki values of 5-HT, (R)(
      )DOI, and VER-3323 for the 5-HT2A, 5-HT2B, and 5-HT2C receptors by SPA format
      were equivalent to published data determined by filtration binding assays. These
      results indicate that agonist binding assays in SPA format can be easily adapted
      to a high throughput assay to screen for selective 5-HT2C receptor agonists, as
      well as for selectivity profiling of the compounds.

PMID- 16438661
TI  - Protein expression plasmids produced rapidly: streamlining cloning protocols and
      robotic handling.
AB  - As many processes in the preclinical drug discovery process become highly
      parallel, the need to also produce a large number of different proteins in
      parallel has become acute, such as for protein crystallization and activity
      screening. In turn, the requisite DNA constructions to produce these proteins
      must now be done at a rate that requires automated cloning procedures, each with
      an intrinsic low failure probability per sample. The high-throughput cloning
      solutions presented here achieve production of 192 different expression plasmids
      at a success rate of greater than 95% of the targeted open reading frames. Time
      for completion of the set by one person is reduced to approximately 11 working
      days, starting with polymerase chain reactions for a number of source clones and
      ending with purified expression plasmids. Achievement of this throughput utilizes
      the following: (1) the Beckman Coulter (Fullerton, CA) Biomek FX liquid handler
      for most manipulations, (2) Gateway cloning technology (Invitrogen Corp.,
      Carlsbad, CA), and (3) computer programs designed for parallel processing of all
      sample information, including primer design and the resulting DNA and protein
      sequence assembly. Exemplary data are presented for discovery of a form of the
      Rho-kinase that crystallizes (ROCK2).

PMID- 16438662
TI  - Optimization, application, and interpretation of lactate dehydrogenase
      measurements in microwell determination of cell number and toxicity.
AB  - The lactate dehydrogenase (LDH) assay was addressed for its sensitivity,
      disturbances by foaming, and cell number and size. Cells were from a U-251 MG
      grade IV human glioblastoma brain tumor cell line used in 100-microl well
      volumes. Cells were counted by microscopy and Coulter counting; assays were LDH
      or trypan blue. The results indicate increased 490 nm signals (level, variance)
      by using phenol red or by increasing fetal bovine serum from 5% to 10%. The data
      also indicate that defoaming results in reduced variances ranging from a factor
      of 2 at 1-3 units of absorption, up to a factor of 4-5 at <1 units of absorption.
      Coulter counting indicated a decrease in cell volume with increasing end-point
      cell density, attributed to general shrinking at increasing density. In
      comparisons, total LDH was considered relative to both cell total volume and cell
      numbers. The result suggests that total LDH should be regarded as reflecting cell
      total volume rather than cell numbers. In a comparative Cu exposure test, signals
      of both LDH and a sodium salt of 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5
      tetrazolio]-1,3-benzene disulfonate (WST-1) decreased with increasing Cu supply,
      while bromodeoxyuridine signals remained largely unaffected. The data show the
      differences in responses in cell viability and proliferation, but, above all,
      indicate that LDH should be expressed on a per cell volume basis rather than per
      cell, to avoid the problem that mere density effects contribute to signals on
      compound or metal toxicity.

PMID- 16438663
TI  - Overview on the analytical tools for quality control of natural product-based
      supplements: a case study of ginseng.
AB  - The quality of pharmaceutical products like ginseng is important for ensuring
      consumer safety and efficacy. Many ginseng products sold today are in various
      formulations such as powder, capsules, tablets, soft-gels, liquid extracts, and
      tea. This renders ginseng less identifiable by smell, taste, or physical
      appearance. Furthermore, as ginseng is expensive, adulteration with other cheaper
      products occurs. Hence quality assurance of ginseng is needed. This paper reviews
      the major techniques for ascertaining the level of ginsenosides, the primary
      active ingredients for ginseng, and covers high-performance liquid, gas, and thin
      layer chromatographies, infrared and nuclear magnetic resonance spectroscopies,
      enzyme immunoassays, and other molecular methods. Supporting techniques such as
      ultraviolet, fluorescence, diode array and evaporative light scattering
      detections, and mass spectrometry will also be touched upon. This review also
      discusses the principles and applications of biosensors-in particular fiber optic
      based sensors-and their feasibility in ginseng analysis based on preliminary
      studies. Despite their potential, there is currently no or limited commercial
      exploitation of fiber optic-based sensors to perform ginseng quality analysis.
      The opportunity for biosensors to be used for the rapid quality surveillance of
      ginseng is appealing, but several key issues still need to be addressed before
      they find widespread applications in the traditional Chinese medicine industry.

PMID- 16438666
TI  - Activity intolerance and impaired physical mobility in elders.
AB  - PURPOSE: To clarify the use of two nursing diagnoses, activity intolerance and
      impaired physical mobility, with elderly patients. METHOD: Ninety-two elders from
      a long-term care facility in Wonju, Korea. A checklist developed by the
      researchers was used for data collection. FINDINGS: Defining characteristics from
      this study related to psychological components of activity intolerance are
      significant in differentiating between the two diagnoses. Using a decision-making
      tree based on data from this study, each nursing diagnosis can be correctly
      identified. CONCLUSIONS: The results of this study are significant in broadening
      the defining characteristics to be used in differentiating between two nursing
      diagnoses. PRACTICE IMPLICATIONS: Clarification of nursing diagnoses serves to
      direct students and nurses to choosing appropriate interventions.

PMID- 16438667
TI  - Nursing diagnoses and interventions of Japanese patients with end-stage breast
      cancer admitted for different care purposes.
AB  - PURPOSE: To clarify actual nursing diagnoses for and interventions given to
      patients with end-stage breast cancer admitted for different care purposes.
      METHODS: Nursing diagnoses, defining characteristics, related/risk factors, and
      nursing interventions were analyzed in a convenience sample of 150 patient
      records. FINDINGS: A total of 539 nursing diagnoses (96 labels) were documented.
      Frequently listed diagnoses were chronic pain, risk for infection, and activity
      intolerance. The most frequently used nursing diagnosis for the chemotherapy
      group was risk for infection. The nurses in this study rarely report any
      diagnoses related to death and dying. CONCLUSIONS: Nursing diagnoses and
      interventions differed depending on the purpose of admission. PRACTICE
      IMPLICATIONS: Oncology nurses need to consider the reasons for admission when
      making nursing diagnoses and interventions for patients with end-stage breast
      cancer.

PMID- 16438668
TI  - Nursing diagnoses identified during parent group meetings in a neonatal intensive
      care unit.
AB  - PURPOSE: To identify nursing diagnoses in the reports of parents obtained during
      parent support group meetings in a neonatal intensive care unit. METHODS: An
      explorative descriptive study using records obtained during 29 meetings over a
      period of 11 months with parents and family members. FINDINGS: Six NANDA-approved
      nursing diagnoses were identified from parent group data: fear, risk for impaired
      parent/infant attachment, parental role conflict, risk for ineffective
      breastfeeding, impaired home maintenance, and risk for caregiver role strain.
      Diagnoses were not validated with parents. DISCUSSION: Support groups helped the
      parents express their thoughts and feelings and provided nurses with
      opportunities to identify nursing diagnoses and interventions. The identification
      of nursing diagnoses showed that nursing interventions that are focused on
      improved parent outcomes should be implemented for parents and other family
      members. IMPLICATIONS: Nursing care in neonatal units should focus on
      interventions for parents and other family members in addition to providing the
      necessary care of newborns.

PMID- 16438669
TI  - Taxonomy of nursing practice: adding an administrative domain.
AB  - PURPOSE: To propose the addition of a fifth domain, Administrative, to the
      Taxonomy of Nursing Practice, and to introduce the related concept of
      organization nursing diagnoses. DATA SOURCES: The Taxonomy of Nursing Practice,
      organizational and nursing management/leadership literature, experience of the
      authors. DATA SYNTHESIS: Analyzing the concept of a taxonomy to capture nursing
      practice revealed an omission of the management/leadership roles assumed by
      nurses in organizational, nurse manager, and staff nurse practice levels. To
      incorporate this administrative practice, an additional domain, Administrative,
      was developed. Nursing diagnoses were oriented to the organization as client,
      hence the addition of organization nursing diagnoses. CONCLUSIONS: Including an
      Administrative Domain in the Taxonomy of Nursing Practice will cover the scope of
      nursing practice and will provide a basis for developing the diagnoses for which
      nurses are accountable within organizations. IMPLICATIONS FOR PRACTICE: Nurses'
      contributions to healthcare organizational function and their effect on patient
      care outcomes will be made more explicit and can more readily be measured with
      terminology that captures the nursing administrative roles at three levels of
      practice.

PMID- 16438670
TI  - Immunology of malaria infections.

PMID- 16438671
TI  - Antigen presentation and dendritic cell biology in malaria.
AB  - Dendritic cells (DCs) are important both in amplifying the innate immune response
      and in initiating adaptive immunity and shaping the type of T helper (Th)
      response. Although the role of DCs in immune responses to many intracellular
      pathogens has been delineated and research is underway to identify the mechanisms
      involved, relatively little is known concerning the role of DCs in immunity to
      malaria. In this review, we provide an overview and summary of previous and
      current studies aimed to investigate the role of DCs as antigen presenting cells
      (APCs). In addition, the role of DCs in inducing innate and adaptive immunity to
      blood-stage malaria is discussed and, where information is available, the
      mechanisms involved are presented. Data from studies in humans infected with
      Plasmodium falciparum, the major human parasite responsible for the high
      morbidity and mortality associated with malaria throughout many regions of the
      developing world, as well as data from experimental mouse models are presented.
      Overall, the data from these studies are conflicting. The possible reasons for
      these differences, including the use of different parasite species and parasite
      strains in the mouse studies, are discussed. Nevertheless, together the data have
      important implications for development of an effective malaria vaccine since the
      selection of appropriate Plasmodium antigens and/or adjuvants, targeting innate
      immune responses involving DCs, may provide optimal protection against malaria.
      It is hoped that this review promotes more investigation among malariologists and
      immunologists alike on DCs and malaria.

PMID- 16438672
TI  - Protective and pathogenic roles of CD8+ T cells during malaria infection.
AB  - CD8+ T cells play a key role in protection against pre-erythrocytic stages of
      malaria infection. Many vaccine strategies are based on the idea of inducing a
      strong infection-blocking CD8+ T cell response. Here, we summarize what is known
      about the development, specificity and protective effect of malaria-specific CD8+
      T cells and report on recent developments in the field. Although work in mouse
      models continues to make progress in our understanding of the basic biology of
      these cells, many questions remain to be answered - particularly on the roles of
      these cells in human infections. Increasing evidence is also emerging of a
      harmful role for CD8+ T cells in the pathology of cerebral malaria in rodent
      systems. Once again, the relevance of these results to human disease is one of
      the primary questions facing workers in this field.

PMID- 16438673
TI  - Priming of CD4+ T cells and development of CD4+ T cell memory; lessons for
      malaria.
AB  - CD4 T cells play a central role in the immune response to malaria. They are
      required to help B cells produce the antibody that is essential for parasite
      clearance. They also produce cytokines that amplify the phagocytic and
      parasitocidal response of the innate immune system, as well as dampening this
      response later on to limit immunopathology. Therefore, understanding the
      mechanisms by which T helper cells are activated and the requirements for
      development of specific, and effective, T cell memory and immunity is essential
      in the quest for a malaria vaccine. In this paper on the CD4 session of the
      Immunology of Malaria Infections meeting, we summarize discussions of CD4 cell
      priming and memory in malaria and in vaccination and outline critical future
      lines of investigation. B. Stockinger and M.K. Jenkins proposed cutting edge
      experimental systems to study basic T cell biology in malaria. Critical
      parameters in T cell activation include the cell types involved, the route of
      infection and the timing and location and cell types involved in antigen
      presentation. A new generation of vaccines that induce CD4 T cell activation and
      memory are being developed with new adjuvants. Studies of T cell memory focus on
      differentiation and factors involved in maintenance of antigen specific T cells
      and control of the size of that population. To improve detection of T cell memory
      in the field, efforts will have to be made to distinguish antigen-specific
      responses from cytokine driven responses.

PMID- 16438674
TI  - Memory B cell responses and malaria.
AB  - Malaria is a serious cause of morbidity and mortality in millions of individuals
      each year. People living in endemic areas build up partial immunity only after
      repeated attacks of malaria over several years. At this meeting we discussed
      current knowledge about long-term protection and the challenges we face in the
      development of an effective malaria vaccine.

PMID- 16438675
TI  - Regulating immunity to malaria.
AB  - The optimal outcome of a malaria infection is that parasitized cells are killed
      and degraded without inducing significant pathology. Since much of the pathology
      of malaria infection can be immune-mediated, this implies that immune responses
      have to be carefully regulated. The mechanisms by which anti-malarial immune
      responses are believed to be regulated were discussed at the recent Malaria
      Immunology Workshop (Bloomberg School of Public Health, Johns Hopkins University,
      Baltimore, Maryland, USA; February 2005). Potential regulatory mechanisms include
      regulatory T cells, which have been shown to significantly modify cellular immune
      responses to various protozoan infections, including leishmania and malaria;
      neutralising antibodies to pro-inflammatory malarial toxins such as
      glycosylphosphatidylinositol and haemozoin; and self-regulating networks of
      effector molecules. Innate and adaptive immune responses are further moderated by
      the broader immunological environment, which is influenced by both the genetic
      background of the host and by co-infection with other pathogens. A detailed
      understanding of the interplay between these different immunoregulatory processes
      may facilitate the rationale design of vaccines and novel therapeutics.

PMID- 16438676
TI  - Immune effector mechanisms in malaria.
AB  - That humans in endemic areas become immune to malaria offers encouragement to the
      idea of developing protective vaccines. However natural immunity is relatively
      inefficient, being bought at the cost of substantial childhood mortality, and
      current vaccines are only partially protective. Understanding potential targets
      and mechanisms of protective immunity is important in the development and
      evaluation of future vaccines. Some of the problems in identifying such targets
      and mechanisms in humans naturally exposed to malaria may stem from conceptual
      and methodological issues related to defining who in a population is susceptible,
      problems in defining immune responsiveness at single time points and issues
      related to antigenic polymorphism, as well as the failure of many current
      approaches to examine functional aspects of the immune response. Protective
      immune responses may be directed to the pre erythrocytic parasite, to the free
      merozoite of the blood stage parasite or to new antigens induced on the infected
      red cell surface. Tackling the methodological issues of defining protection and
      immune response, together with studies that combine functional assays with new
      approaches such as allelic exchange and gene knock out offer opportunities for
      better defining key targets and mechanisms.

PMID- 16438677
TI  - RNA thermometers.
AB  - Temperature is an important parameter that free-living cells monitor constantly.
      The expression of heat-shock, cold-shock and some virulence genes is coordinated
      in response to temperature changes. Apart from protein-mediated transcriptional
      control mechanisms, translational control by RNA thermometers is a widely used
      regulatory strategy. RNA thermometers are complex RNA structures that change
      their conformation in response to temperature. Most, but not all, RNA
      thermometers are located in the 5'-untranslated region and mask ribosome-binding
      sites by base pairing at low temperatures. Melting of the structure at increasing
      temperature permits ribosome access and translation initiation. Different cis
      acting RNA thermometers and a trans-acting thermometer will be presented.

PMID- 16438678
TI  - Haloarchaeal proteases and proteolytic systems.
AB  - Proteases play key roles in many biological processes and have numerous
      applications in biotechnology and industry. Recent advances in the genetics,
      genomics and biochemistry of the halophilic Archaea provide a tremendous
      opportunity for understanding proteases and their function in the context of an
      archaeal cell. This review summarizes our current knowledge of haloarchaeal
      proteases and provides a reference for future research.

PMID- 16438679
TI  - Role of mycobacterial efflux transporters in drug resistance: an unresolved
      question.
AB  - Two mechanisms are thought to be involved in the natural drug resistance of
      mycobacteria: the mycobacterial cell wall permeability barrier and active
      multidrug efflux pumps. Genes encoding drug efflux transporters have been
      isolated from several mycobacterial species. These proteins transport
      tetracycline, fluoroquinolones, aminoglycosides and other compounds. Recent
      reports have suggested that efflux pumps may also be involved in transporting
      isoniazid, one of the main drugs used to treat tuberculosis. This review
      highlights recent advances in our understanding of efflux-mediated drug
      resistance in mycobacteria, including the distribution of efflux systems in these
      organisms, their substrate profiles and their contribution to drug resistance.
      The balance between the drug transport into the cell and drug efflux is not yet
      clearly understood, and further studies are required in mycobacteria.

PMID- 16438680
TI  - Fungal heat-shock proteins in human disease.
AB  - Heat-shock proteins (hsps) have been identified as molecular chaperones conserved
      between microbes and man and grouped by their molecular mass and high degree of
      amino acid homology. This article reviews the major hsps of Saccharomyces
      cerevisiae, their interactions with trehalose, the effect of fermentation and the
      role of the heat-shock factor. Information derived from this model, as well as
      from Neurospora crassa and Achlya ambisexualis, helps in understanding the
      importance of hsps in the pathogenic fungi, Candida albicans, Cryptococcus
      neoformans, Aspergillus spp., Histoplasma capsulatum, Paracoccidioides
      brasiliensis, Trichophyton rubrum, Phycomyces blakesleeanus, Fusarium oxysporum,
      Coccidioides immitis and Pneumocystis jiroveci. This has been matched with
      proteomic and genomic information examining hsp expression in response to noxious
      stimuli. Fungal hsp90 has been identified as a target for immunotherapy by a
      genetically recombinant antibody. The concept of combining this antibody fragment
      with an antifungal drug for treating life-threatening fungal infection and the
      potential interactions with human and microbial hsp90 and nitric oxide is
      discussed.

PMID- 16438681
TI  - Feast/famine regulatory proteins (FFRPs): Escherichia coli Lrp, AsnC and related
      archaeal transcription factors.
AB  - Feast/famine regulatory proteins comprise a diverse family of transcription
      factors, which have been referred to in various individual identifications,
      including Escherichia coli leucine-responsive regulatory protein and asparagine
      synthase C gene product. A full length feast/famine regulatory protein consists
      of the N-terminal DNA-binding domain and the C-domain, which is involved in
      dimerization and further assembly, thereby producing, for example, a disc or a
      chromatin-like cylinder. Various ligands of the size of amino acids bind at the
      interface between feast/famine regulatory protein dimers, thereby altering their
      assembly forms. Also, the combination of feast/famine regulatory protein subunits
      forming the same assembly is altered. In this way, a small number of feast/famine
      regulatory proteins are able to regulate a large number of genes in response to
      various environmental changes. Because feast/famine regulatory proteins are
      shared by archaea and eubacteria, the genome-wide regulation by feast/famine
      regulatory proteins is traceable back to their common ancestor, being the
      prototype of highly differentiated transcription regulatory mechanisms found in
      organisms nowadays.

PMID- 16438682
TI  - Fungi growing on aromatic hydrocarbons: biotechnology's unexpected encounter with
      biohazard?
AB  - The biodegradation of aromatic hydrocarbons by fungi has traditionally been
      considered to be of a cometabolic nature. Recently, however, an increasing number
      of fungi isolated from air biofilters exposed to hydrocarbon-polluted gas streams
      have been shown to assimilate volatile aromatic hydrocarbons as the sole source
      of carbon and energy. The biosystematics, ecology, and metabolism of such fungi
      are reviewed here, based in part on re-evaluation of a collection of published
      hydrocarbon-degrading isolates obtained from authors around the world. Incorrect
      or outdated identifications in original publications are corrected by ribosomal
      DNA sequence analysis. The data show that many volatile-hydrocarbon-degrading
      strains are closely related to, or in some cases clearly conspecific with, the
      very restricted number of human-pathogenic fungal species causing severe mycoses,
      especially neurological infections, in immunocompetent individuals.
      Neurochemistry features a distinctive array of phenolic and aliphatic compounds
      that are related to molecules involved in the metabolism of aromatic
      hydrocarbons. Hence, there may be physiological connections between hydrocarbon
      assimilation and certain patterns of mammalian infection.

PMID- 16438683
TI  - Of microbe and man: determinants of Helicobacter pylori-related diseases.
AB  - The human gastric pathogen Helicobacterpylori infects the human gastric mucus
      layer of approximately half of the world's population. Colonization with this
      bacterium results in superficial gastritis without clinical symptoms, but can
      progress into gastric or duodenal ulcers, gastric malignancies and mucosa
      associated lymphoid tissue-lymphomas. Disease outcome is affected by a complex
      interplay between host, environmental and bacterial factors. Irrespective of
      disease outcome, the majority of H. pylori infected individuals remain colonized
      for life. Changing conditions in the human gastric mucosa may alter gene
      expression and/or result in the outgrowth of more fit H. pylori variants. As
      such, H. pylori is a highly flexible organism that is optimally adapted to its
      host. the heterogeneity in H. pylori populations make predictions on H. pylori
      related pathogenesis difficult. In this review, we discuss host, environmental
      and bacterial factors that are important in disease progression. Moreover, H.
      pylori adaptive mechanisms, which allow its life-long survival and growth in the
      gastric mucosa are considered.

PMID- 16438684
TI  - An approach to the systematic distortion correction in aberration-corrected HAADF
      images.
AB  - Systematic distortion has been analysed in high-angle annular dark-field (HAADF)
      images which may be caused by electrical interference. Strain mapping techniques
      have been applied to a strain-free GaAs substrate in order to provide a broad
      analysis of the influence of this distortion on the determination of local strain
      in the heterostructure. We have developed a methodology for estimating the
      systematic distortion, and we correct the original images by using an algorithm
      that removes this systematic distortion.

PMID- 16438685
TI  - Microstructure of pharyngeal tooth enameloid in the parrotfish Scarus rivulatus
      (Pisces: Scaridae).
AB  - The microstructure of parrotfish pharyngeal teeth was examined using scanning
      electron microscopy to infer possible mechanical properties of the dentition with
      respect to their function. Parrotfish tooth enameloid is formed from fluorapatite
      crystals grouped into bundles. In the upper and lower pharyngeal jaw, the
      majority of the crystal bundles are orientated either perpendicularly or
      vertically to the enameloid surface. The only exception is in the trailing apical
      enameloid in which the majority of bundles are orientated perpendicularly or
      horizontally to the trailing surface. A distinct transition occurs through the
      middle of the apex between the leading and trailing enameloid in teeth of the
      lower pharyngeal jaw. This transition appears less distinct in the teeth of the
      upper pharyngeal jaw. Enameloid microstructure indicates that shear forces
      predominate at the apex of the teeth. In the remainder of the enameloid, the
      microstructure indicates that wear is predominant, and the shear forces are of
      less importance.

PMID- 16438686
TI  - Bitumen morphologies by phase-detection atomic force microscopy.
AB  - Summary Bitumen is a complex mixture of hydrocarbons for which microstructural
      knowledge is incomplete. In an effort to detail this microstructure, 13 bitumens
      were analysed by phase-detection atomic force microscopy. Based on morphology,
      the bitumens could be classified into three distinct groups. One group showed
      fine domains down to 0.1 microm, another showed domains of about 1 microm, and a
      third group showed up to four different domains or phases of different sizes and
      shapes. No correlation was found between the atomic force microscopy morphology
      and the composition based on asphaltenes, polar aromatics, naphthene aromatics
      and saturates. A high correlation was found between the area of the 'bee-like'
      structures and the vanadium and nickel content in bitumen, and between the atomic
      force microscopy groups and the average size of molecular planes made of fused
      aromatics. The morphology and the molecular arrangements in bitumen thus appear
      to be partly governed by the molecular planes and the polarity defined by
      metallic cations.

PMID- 16438688
TI  - Aspects regarding measurement of thickness of intergranular glassy films.
AB  - Materials such as Si(3)N(4), SiC and SrTiO(3) can have grain boundaries
      characterized by the presence of a thin intergranular amorphous film of nearly
      constant thickness, in some cases (e.g. Si(3)N(4)) almost independent of the
      orientation of the bounding grains, but dependent on the composition of the
      ceramic. Microscopy techniques such as high-resolution lattice fringe imaging,
      Fresnel fringe imaging and diffuse dark field imaging have been applied to the
      study of intergranular glassy films. The theme of the current investigation is
      the use of Fresnel fringes and Fourier filtering for the measurement of the
      thickness of intergranular glassy films. Fresnel fringes hidden in high
      resolution micrographs can be used to objectively demarcate the glass-crystal
      interface and to measure the thickness of intergranular glassy films. Image line
      profiles obtained from Fourier filtering the high-resolution micrographs can
      yield better estimates of the thickness. Using image simulation, various kinds of
      deviation from an ideal square-well potential profile and their effects on the
      Fresnel image contrast are considered. A method is also put forth to objectively
      retrieve Fresnel fringe spacing data by Fourier filtering Fresnel contrast
      images. Difficulties arising from the use of the standard Fresnel fringe
      extrapolation technique are outlined and an alternative method for the
      measurement of the thickness of intergranular glassy films, based on zero-defocus
      (in-focus) Fresnel contrast images is suggested. The experimental work is from
      two ceramic systems: Lu-Mg-doped Si(3)N(4) and SrTiO(3) (stoichiometric and
      nonstoichiometric). Further, a comparison is made between the standard high
      resolution lattice fringe technique, the standard Fresnel fringe extrapolation
      technique and the methods of analyses introduced in the current work, to
      illustrate their utility and merits. Taking experimental difficulties into
      account, this work is intended to be a practical tool kit for the study of
      intergranular glassy films.

PMID- 16438689
TI  - On the accuracy of lattice-distortion analysis directly from high-resolution
      transmission electron micrographs.
AB  - Lattice-distortion analysis from high-resolution transmission electron
      micrographs offers a convenient and fast tool for direct measurement of strains
      in materials over a large area. In the present work, we have evaluated the
      accuracy of the strain measurement when the effects of the realistic experimental
      variables are explicitly taken into account by the use of image simulation
      techniques. These variables are focal setting and variation, local thickness and
      orientation of the sample, as well as misalignments of the sample and the
      incident beam. The evaluation reveals that consistency of image features and
      contrast within the micrographs is desired for the analysis to eliminate effects
      of the variations of local focus value and specimen thickness. After proper
      orientation of a crystalline specimen, the mis-orientation of the object will not
      notably influence the strain measurement even though a local bending may exist
      within the sample. However, the incident beam of the microscope needs to be
      aligned carefully as the beam misalignment may introduce a notable artefact
      around the interface region.

PMID- 16438687
TI  - Three-dimensional volume reconstruction of extracellular matrix proteins in uveal
      melanoma from fluorescent confocal laser scanning microscope images.
AB  - The distribution of looping patterns of laminin in uveal melanomas and other
      tumours has been associated with adverse outcome. Moreover, these patterns are
      generated by highly invasive tumour cells through the process of vasculogenic
      mimicry and are not therefore blood vessels. Nevertheless, these extravascular
      matrix patterns conduct plasma. The three-dimensional (3D) configuration of these
      laminin-rich patterns compared with blood vessels has been the subject of
      speculation and intensive investigation. We have developed a method for the 3D
      reconstruction of volume for these extravascular matrix proteins from serial
      paraffin sections cut at 4 microm thicknesses and stained with a fluorescently
      labelled antibody to laminin (Maniotis et al., 2002). Each section was examined
      via confocal laser-scanning focal microscopy (CLSM) and 13 images were recorded
      in the Z-dimension for each slide. The input CLSM imagery is composed of a set of
      3D sub-volumes (stacks of 2D images) acquired at multiple confocal depths, from a
      sequence of consecutive slides. Steps for automated reconstruction included (1)
      unsupervised methods for selecting an image frame from a sub-volume based on
      entropy and contrast criteria, (2) a fully automated registration technique for
      image alignment and (3) an improved histogram equalization method that
      compensates for spatially varying image intensities in CLSM imagery due to photo
      bleaching. We compared image alignment accuracy of a fully automated method with
      registration accuracy achieved by human subjects using a manual method. Automated
      3D volume reconstruction was found to provide significant improvement in
      accuracy, consistency of results and performance time for CLSM images acquired
      from serial paraffin sections.

PMID- 16438690
TI  - A simple and stable auto focusing protocol for long multidimensional live cell
      microscopy.
AB  - Focus maintenance is a challenging problem in multidimensional wide-field
      microscopy. Most automated microscopes use software algorithms, which are applied
      to z-sections of the object, to select for the plane with the best signal to
      noise ratio. When applied automatically in multidimensional imaging applications,
      auto focus routines significantly increase light exposure and can become
      cytotoxic if applied too frequently. In addition, automated focusing procedures
      can readily focus on unwanted high contrast objects. By labelling a defined
      position with a fluorescent marker, we were able to separate the focusing
      procedure from the actual image acquisition positions and therefore overcome some
      of the major drawbacks of routine auto focus procedures. To implement this method
      in a multidimensional acquisition experiment, we created a visual basic-based
      program, which is run prior to each image acquisition. This technique allows
      tight control of focus whilst keeping light toxicity in live cell imaging
      experiments to a minimum.

PMID- 16438692
TI  - Co-existence of ununited anconeal process and fragmented medial coronoid process
      of the ulna in the dog.
AB  - OBJECTIVES: To determine the incidence of fragmented medial coronoid process of
      the ulna in dogs with ununited anconeal process. The efficacy of presurgical
      radiography to diagnose the co-existence of these diseases was also investigated.
      METHODS: One hundred and fifty-five joints from 137 dogs with ununited anconeal
      process were included in the study. For the radiographic examinations, an
      extended mediolateral projection and a craniolateral-caudomedial oblique
      projection of each elbow joint were taken before surgery. Inspection of the
      medial part of the joint was carried out either by arthrotomy or arthroscopy.
      RESULTS: Seventy-two per cent of the dogs were German shepherd dogs. In 25 joints
      (16 per cent) a fragmented medial coronoid process was diagnosed and removed via
      arthrotomy or arthroscopy. The co-existence of a fragmented medial coronoid
      process was diagnosed correctly in only 13 cases (52 per cent) by radiography. In
      five of these cases with advanced osteoarthritis, the fragment was directly
      visible because of its dislocation. Compared with published information, the
      occurrence of ununited anconeal process with fragmented medial coronoid process
      is noted more frequently in the present study. CLINICAL SIGNIFICANCE: It can be
      summarised that if ununited anconeal process is present, it is not usually
      possible to clearly identify fragmented medial coronoid process by radiography.
      Therefore, it is important to be able to inspect the medial aspect of the joint
      concerned during surgery.

PMID- 16438693
TI  - Use of reconstructed computed tomography for the assessment of joint spaces in
      the canine elbow.
AB  - OBJECTIVES: To assess the accuracy of reconstructed computed tomography for
      imaging canine elbow joint spaces. METHODS: Computed tomography scans of eight
      cadaveric elbows were obtained and reconstructed computed tomography images were
      formatted in the dorsal and sagittal planes. Humeroradial and humeroulnar joint
      space measurements were obtained from these images. Intra-observer and inter
      observer variations in joint space measurements were assessed, as was the effect
      of specimen positioning (inter-image variation). After freezing, four elbows were
      sectioned in the dorsal plane and four in the sagittal plane. In addition to
      visual comparison of the frozen sections with reconstructed computed tomography
      images, joint space measurements were obtained from frozen sections and compared
      with those from reconstructed computed tomography images. Variation was assessed
      using statistical calculations and graphical techniques. RESULTS: Both inter
      image and intra-observer analyses revealed good agreement and low variation
      between data sets. Inter-observer correlation was only moderate, though variation
      was low. Visually, the reconstructed computed tomography images accurately
      reflected the frozen section anatomy. Agreement between frozen section and
      reconstructed computed tomography joint space measurements was good, with minimal
      variation. CLINICAL SIGNIFICANCE: These results indicate that reconstructed
      computed tomography is capable of accurately imaging elbow joint spaces and
      precise joint space measurements can be obtained. Reconstructed computed
      tomography may be useful for determining joint space measurements and detecting
      elbow incongruencies in dogs with elbow dysplasia.

PMID- 16438694
TI  - Genetic analysis of three different classification protocols for the evaluation
      of elbow dysplasia in German shepherd dogs.
AB  - OBJECTIVES: Three different scoring systems for elbow dysplasia and its
      radiographic signs were genetically evaluated in 2645 German shepherd dogs.
      METHODS: An animal model was used to estimate heritabilities and additive genetic
      and residual correlations for the three scoring systems: ED-SV, which is
      recommended by the International Elbow Working Group; ED-LA, developed by Lang
      and others; and ED-TH, proposed by Tellhelm. RESULTS: The effects of sex, age at
      examination and the correlation between the two factors were significant for all
      three scoring systems. Heritability estimates (se) were 0.18 (0.04) for ED-SV,
      0.11 (0.03) for ED-LA and 0.16 (0.04) for ED-TH. The additive genetic
      correlations among the different single criteria for elbow dysplasia and the
      different elbow dysplasia scores were between 0.68 and 0.98, except for the
      criteria ununited anconeal process and osteochondrosis dissecans of the trochlea
      humeri, which were mostly genetically negatively correlated to the other
      radiological criteria. CLINICAL SIGNIFICANCE: The elbow dysplasia scores were
      determined by two genetically different traits. The possibilities for selecting
      German shepherd dogs with respect to elbow dysplasia might be improved by taking
      into account these two traits in the prediction of breeding values.

PMID- 16438695
TI  - Treatment of inherently unstable open or infected fractures by open wound
      management and external skeletal fixation.
AB  - OBJECTIVES: To assess the use of external skeletal fixation with open wound
      management for the treatment of inherently unstable open or infected fractures in
      dogs. METHODS: A retrospective review of 10 cases. RESULTS: Fracture
      stabilisation and wound management required only a single anaesthetic, and
      despite the challenging nature of these injuries, the final outcome was
      acceptable or good in every case. However, minor complications associated with
      the fixator pins were quite common, and two dogs developed complications which
      required additional surgery. CLINICAL SIGNIFICANCE: Open management of wounds,
      even when bone was exposed, proved to be an effective technique, and external
      skeletal fixators were usually effective at maintaining stability throughout an
      inevitably extended fracture healing period.

PMID- 16438696
TI  - Y-T humeral fractures with supracondylar comminution in five cats.
AB  - Five cats with Y-T fractures of the humeral condyle were reviewed. Breeds
      presented included domestic shorthair (four cats) and Maine Coon (one cat). Age
      ranged from two to 16 years. All the cats were neutered males. A road traffic
      accident was suspected in all cases. Four of the fractures were severely
      comminuted and one fracture had four fragments. The fractures were repaired via
      combined medial and lateral approaches. Fixation of the epicondylar ridges was
      performed using buttress plates in four cases and neutralisation plates in one
      case. The intracondylar fracture was stabilised using a 2.7 mm lag screw in four
      cases and a 3.5 mm lag screw in the other. A corticocancellous bone graft was
      applied in two cases. The intracondylar fracture was accurately reduced in all
      cases. Complete radiographic healing was documented in two cases 6 and 11 weeks
      following surgery. Failure of the fixation occurred in the most severely
      comminuted fracture five days postoperatively. Surgical revision was not
      performed, and the limb was amputated. Three cats were free of lameness and had
      resumed outdoor activities at follow-up (five to eight months after surgery).
      Marked lameness due to loss of elbow movement was observed in the other case.

PMID- 16438697
TI  - Traumatic triceps tendon avulsion in a cat.
AB  - Traumatic avulsion of the triceps tendon was diagnosed in a 15-month-old, male,
      neutered European shorthair cat. Diagnosis was established clinically by
      palpation of a transverse groove proximal to the olecranon and by radiography.
      The avulsed end of the tendon was surgically reapposed using a modified three
      loop pulley suture and horizontal mattress sutures. Postoperatively, elbow
      flexion was limited for three weeks with the aid of a spica splint and by
      exercise restriction for six weeks. The cat showed no lameness after bandage
      removal up to the time of writing (seven months). Although rare, triceps tendon
      injuries can occur after a blunt trauma and should be included in the
      differential diagnosis of foreleg lameness in the cat. The modified three-loop
      pulley suture in combination with subsequent immobilisation of the limb with a
      splinted bandage resulted in a successful outcome in this cat with a triceps
      tendon avulsion.

PMID- 16438698
TI  - Treatment of distal diaphyseal fractures using hybrid external skeletal fixation
      in three dogs.
AB  - Stabilisation of distal diaphyseal/metaphyseal fractures or osteotomies of the
      tibia and the radius is challenging due to the small fragment size, with
      innovative implants and external skeletal fixation systems described for their
      management. Hybrid external skeletal fixation is a novel external fixation system
      for use in small animals. This case series describes the management of distal
      diaphyseal fractures with IMEX-SK hybrid external skeletal fixation in three
      canine patients. Fracture healing was achieved in all cases, with frame removal
      after 5 to 10 weeks. Minimal complications were encountered in two cases. IMEX-SK
      hybrid external skeletal fixation constructs provide the veterinary surgeon with
      another option in the management of distal diaphyseal/metaphyseal fractures.

PMID- 16438699
TI  - What is your diagnosis? A case of intervertebral disc protrusion in a cat:
      lymphosarcoma.

PMID- 16438706
TI  - Limb-shaking Transient Ischemic Attacks: case report and review of literature.
AB  - BACKGROUND: Limb shaking Transient Ischemic Attack is a rare manifestation of
      carotid-occlusive disease. The symptoms usually point towards a seizure like
      activity and misdiagnosed as focal seizures. On careful history the rhythmic
      seizure like activity reveals no Jacksonian march mainly precipitated by
      maneuvers which lead to carotid compression. We here present a case of an elderly
      gentleman who was initially worked up as suffering from epileptic discharge and
      then later on found to have carotid occlusion. CASE PRESENTATION: Elderly
      gentleman presented with symptoms of rhythmic jerky movements of the left arm and
      both the lower limbs. Clinical suspicion of focal epilepsy was made and EEG, MRI
      Brain with MRA were done. EEG and MRI-Brain revealed normal findings but the MRA
      revealed complete occlusion of right internal carotid artery. On a follow-up
      visit jerky movements of the left arm were precipitated by hyperextension and a
      tremor of 3-4 Hz was revealed. Based on this the diagnosis of low flow TIA was
      made the patient was treated conservatively with adjustment of his anti
      hypertensive and anti-platelet medications. CONCLUSION: Diagnosis of limb-shaking
      TIA is important and should be differentiated from other disorders presenting as
      tremors. Timely diagnosis is important as these patients are shown to benefit
      from reperfusion procedures either surgical or radiological reducing their risk
      of stroke.

PMID- 16438708
TI  - Prevalence of virulence factors in Staphylococcus intermedius isolates from dogs
      and pigeons.
AB  - BACKGROUND: Staphylococcus intermedius has been isolated from healthy dogs and
      pigeons as well as diseased dogs. Similar to Staphylococcus aureus, S.
      intermedius is known to carry many virulence factors but most of these factors
      remain to be studied. In this study, we examined 106 S. intermedius isolates (44
      dog isolates and 62 pigeon isolates) for their hemolytic activity, biofilm
      formation, protease activity, and clumping factor and protein A production.
      RESULTS: Forty-three dog isolates (97.7%) and all pigeon isolates were hemolytic
      on sheep RBCs with a mean hemolytic titer of 336.7 and 47.32, respectively,
      whereas 43 dog isolates (97.7%) and 11 pigeon isolates (17.7%) exhibited a
      significant difference in their hemolytic activity on rabbit RBCs with a mean
      hemolytic titer of 11.04 and 3.76, respectively (p < 0.0005). The mean biofilm
      formation activity for dog isolates was 0.49, which was significantly higher than
      that (0.33) for pigeon isolates (p < 0.0005). Twenty-four dog isolates (54.5%)
      and 11 pigeon isolates (17.7%) were protease positive. Twenty-four dog isolates
      (54.5%) were clumping factor- and protein A- positive. CONCLUSION: S. intermedius
      strains carrying the virulence factors examined in this study were more prevalent
      in dogs than pigeons.

PMID- 16438707
TI  - Comparative analysis of cancer genes in the human and chimpanzee genomes.
AB  - BACKGROUND: Cancer is a major medical problem in modern societies. However, the
      incidence of this disease in non-human primates is very low. To study whether
      genetic differences between human and chimpanzee could contribute to their
      distinct cancer susceptibility, we have examined in the chimpanzee genome the
      orthologous genes of a set of 333 human cancer genes. RESULTS: This analysis has
      revealed that all examined human cancer genes are present in chimpanzee, contain
      intact open reading frames and show a high degree of conservation between both
      species. However, detailed analysis of this set of genes has shown some
      differences in genes of special relevance for human cancer. Thus, the chimpanzee
      gene encoding p53 contains a Pro residue at codon 72, while this codon is
      polymorphic in humans and can code for Arg or Pro, generating isoforms with
      different ability to induce apoptosis or interact with p73. Moreover, sequencing
      of the BRCA1 gene has shown an 8 Kb deletion in the chimpanzee sequence that
      prematurely truncates the co-regulated NBR2 gene. CONCLUSION: These data suggest
      that small differences in cancer genes, as those found in tumor suppressor genes,
      might influence the differences in cancer susceptibility between human and
      chimpanzee. Nevertheless, further analysis will be required to determine the
      exact contribution of the genetic changes identified in this study to the
      different cancer incidence in non-human primates.

PMID- 16438709
TI  - House officer procedure documentation using a Personal Digital Assistant: a
      longitudinal study.
AB  - BACKGROUND: Personal Digital Assistants (PDAs) have been integrated into daily
      practice for many emergency physicians and house officers. Few objective data
      exist that quantify the effect of PDAs on documentation. The objective of this
      study was to determine whether use of a PDA would improve emergency medicine
      house officer documentation of procedures and patient resuscitations. METHODS:
      Twelve first-year Emergency Medicine (EM) residents were provided a Palm V (Palm,
      Inc., Santa Clara, California, USA) PDA. A customizable patient procedure and
      encounter program was constructed and loaded into each PDA. Residents were
      instructed to enter information on patients who had any of 20 procedures
      performed, were deemed clinically unstable, or on whom follow-up was obtained.
      These data were downloaded to the residency coordinator's desktop computer on a
      weekly basis for 36 months. The mean number of procedures and encounters
      performed per resident over a three year period were then compared with those of
      12 historical controls from a previous residency class that had recorded the same
      information using a handwritten card system for 36 months. Means of both groups
      were compared a two-tailed Student's t test with a Bonferroni correction for
      multiple comparisons. One hundred randomly selected entries from both the PDA and
      handwritten groups were reviewed for completeness. Another group of 11 residents
      who had used both handwritten and PDA procedure logs for one year each were asked
      to complete a questionnaire regarding their satisfaction with the PDA system.
      RESULTS: Mean documentation of three procedures significantly increased in the
      PDA vs handwritten groups: conscious sedation 24.0 vs 0.03 (p = 0.001);
      thoracentesis 3.0 vs 0.0 (p = 0.001); and ED ultrasound 24.5 vs. 0.0 (p = 0.001).
      In the handwritten cohort, only the number of cardioversions/defibrillations
      (26.5 vs 11.5) was statistically increased (p = 0.001). Of the PDA entries, 100%
      were entered completely, compared to only 91% of the handwritten group, including
      4% that were illegible. 10 of 11 questioned residents preferred the PDA procedure
      log to a handwritten log (mean +/- SD Likert-scale score of 1.6 +/- 0.9).
      CONCLUSION: Overall use of a PDA did not significantly change EM resident
      procedure or patient resuscitation documentation when used over a three-year
      period. Statistically significant differences between the handwritten and PDA
      groups likely represent alterations in the standard of ED care over time.
      Residents overwhelmingly preferred the PDA procedure log to a handwritten log and
      more entries are complete using the PDA. These favorable comparisons and the
      numerous other uses of PDAs may make them an attractive alternative for resident
      documentation.

PMID- 16438710
TI  - Estimating health workforce needs for antiretroviral therapy in resource-limited
      settings.
AB  - BACKGROUND: Efforts to increase access to life-saving treatment, including
      antiretroviral therapy (ART), for people living with HIV/AIDS in resource-limited
      settings has been the growing focus of international efforts. One of the greatest
      challenges to scaling up will be the limited supply of adequately trained human
      resources for health, including doctors, nurses, pharmacists and other skilled
      providers. As national treatment programmes are planned, better estimates of
      human resource needs and improved approaches to assessing the impact of different
      staffing models are critically needed. However there have been few systematic
      assessments of staffing patterns in existing programmes or of the estimates being
      used in planning larger programmes. METHODS: We reviewed the published literature
      and selected plans and scaling-up proposals, interviewed experts and collected
      data on staffing patterns at existing treatment sites through a structured survey
      and site visits. RESULTS: We found a wide range of staffing patterns and patient
      provider ratios in existing and planned treatment programmes. Many factors
      influenced health workforce needs, including task assignments, delivery models,
      other staff responsibilities and programme size. Overall, the number of health
      care workers required to provide ART to 1000 patients included 1-2 physicians, 2
      7 nurses, <1 to 3 pharmacy staff, and a much wider range of counsellors and
      treatment supporters. We estimate from these data that the equivalent of 20,000
      to 100,000 physicians, nurses, pharmacists and other core clinical staff will be
      needed to meet the WHO target of treating 3 million people by the end of 2005.
      The total number of staff, including counsellors, administrators and other
      cadres, could be substantially higher. DISCUSSION: These data are consistent with
      other estimates of human resource requirements for antiretroviral therapy, but
      highlight the considerable variability of current staffing models and the
      importance of a broad range of factors in determining personnel needs. Few
      outcome or cost data are currently available to assess the effectiveness and
      efficiency of different staffing models, and it will be important to develop
      improved methods for gathering this information as treatment programmes are
      scaled up.

PMID- 16438711
TI  - Structural ambiguity of the Chinese version of the Hospital Anxiety and
      Depression Scale in patients with coronary heart disease.
AB  - BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) is a widely used
      screening tool designed as a case detector for clinically relevant anxiety and
      depression. Recent studies of the HADS in coronary heart disease (CHD) patients
      in European countries suggest it comprises three, rather than two, underlying sub
      scale dimensions. The factor structure of the Chinese version of the HADS was
      evaluated in patients with CHD in mainland China. METHODS: Confirmatory factor
      analysis (CFA) was conducted on self-report HADS forms from 154 Chinese CHD
      patients. RESULTS: Little difference was observed in model fit between best
      performing three-factor and two-factor models. CONCLUSION: The current
      observations are inconsistent with recent studies highlighting a dominant
      underlying tri-dimensional structure to the HADS in CHD patients. The Chinese
      version of the HADS may perform differently to European language versions of the
      instrument in patients with CHD.

PMID- 16438712
TI  - The effect of verbalization strategy on Wisconsin Card Sorting Test performance
      in schizophrenic patients receiving classical or atypical antipsychotics.
AB  - BACKGROUND: A number of reports showed en encouraging remediation in some
      patients' executive deficits thanks to the use of 'information processing
      strategies'. Moreover the impact of antipsychotics on cognitive functions of the
      schizophrenics is an important issue, especially if an integrated psychosocial
      treatment is needed. The aim of this paper is to evaluate different executive
      performance and response to verbalization, a strategy of the Wisconsin Card
      Sorting Test (WCST) remediation, in subjects on classical vs atypical
      antipsychotic (AP) treatment. METHODS: Sixty-three schizophrenic subjects
      undertook the WCST under standard and modified (verbalization) administration.
      Subjects were stratified by the kind of WCST response (i.e. good, poor and
      remediable) and AP treatment (i.e. atypical vs. classical). RESULTS: Subjects on
      atypical APs showed a better performance than those on classical ones. More poor
      performers who did not remediate were seen in the sample with classical Aps while
      subjects who remediated the performance were seen in the subgroup with atypical
      APs only. An increase of perseverative and total errors was seen in poor
      performers subjects on classical APs. CONCLUSION: Subjects on atypicals showed a
      better cognitive pattern in terms of WCST performance. Since the naturalistic
      assignment of medication we cannot draw conclusions about its effect on cognitive
      performance and its interaction with cognitive remediation potential. However the
      data lead us to hypothesize that subjects with potential room for remediation did
      so with the atypical APs.

PMID- 16438713
TI  - The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in
      South African women with cervical cancer and control women.
AB  - BACKGROUND: Cervical cancer is due to infection with specific high-risk types of
      human papillomavirus (HPV). Although the incidence of genital HPV infection in
      various population groups is high, most of these regress without intervention.
      Investigating genetic host factors and cellular immune responses, particularly
      cytokines, could help to understand the association between genital HPV infection
      and carcinogenesis. The tumor necrosis factor alpha (TNF-alpha) cytokine plays an
      important role in all stages of cervical cancer and has the ability to induce the
      regression of human tumors. Therefore the aim of the study was to investigate the
      allelic distribution of -308 TNF-alpha gene polymorphism in South African women
      with cervical cancer compared to control women. METHODS: Included in our study
      were women with histologically proven cancer of the cervix (n = 244) and hospital
      based controls (n = 228). All patients and controls were from mixed race and
      black population groups in South Africa. The detection of a bi-allelic -308 (A/G)
      polymorphism in the promoter region of TNF-alpha was investigated using the
      amplification refractory mutation system-polymerase chain reaction (ARMS-PCR)
      technique. The distributions of the allelic frequencies were stratified in both
      patients and controls into two South African ethnic population groups. RESULTS:
      In this study we observed no association between the distribution of -308 TNF
      alpha polymorphism and the risk of developing cervical cancer even after
      combining the data from the two ethnic populations (X2 = 2.26). In addition,
      using the chi-squared test we found no significant association between the known
      risk factors for cervical cancer and the allele distribution of -308 TNF-alpha.
      However, the frequency of the rare high-producing allele -308A of TNF-alpha was
      significantly lower in the South African population when compared to Caucasians
      and Chinese population groups. CONCLUSION: We demonstrated no association between
      -308 TNF-alpha polymorphism and the risk of cervical cancer among two South
      African ethnic population groups. However, as the distribution of the -308A TNF
      alpha was notably different between the control groups of South Africa and other
      population groups this result suggests that ethnic disparity may influence the
      levels of TNF-alpha produced.

PMID- 16438714
TI  - Pulmonary toxicity screening studies in male rats with TiO2 particulates
      substantially encapsulated with pyrogenically deposited, amorphous silica.
AB  - The aim of this study was to evaluate the acute lung toxicity in rats of
      intratracheally instilled TiO2 particles that have been substantially
      encapsulated with pyrogenically deposited, amorphous silica. Groups of rats were
      intratracheally instilled either with doses of 1 or 5 mg/kg of hydrophilic
      Pigment A TiO2 particles or doses of 1 or 5 mg/kg of the following control or
      particle-types: 1) R-100 TiO2 particles (hydrophilic in nature); 2) quartz
      particles, 3) carbonyl iron particles. Phosphate-buffered saline (PBS) instilled
      rats served as additional controls. Following exposures, the lungs of PBS and
      particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid
      inflammatory markers, cell proliferation, and by histopathology at post
      instillation time points of 24 hrs, 1 week, 1 month and 3 months. The
      bronchoalveolar lavage results demonstrated that lung exposures to quartz
      particles, at both concentrations but particularly at the higher dose, produced
      significant increases vs. controls in pulmonary inflammation and cytotoxicity
      indices. Exposures to Pigment A or R-100 TiO2 particles produced transient
      inflammatory and cell injury effects at 24 hours postexposure (pe), but these
      effects were not sustained when compared to quartz-related effects. Exposures to
      carbonyl iron particles or PBS resulted only in minor, short-term and reversible
      lung inflammation, likely related to the effects of the instillation procedure.
      Histopathological analyses of lung tissues revealed that pulmonary exposures to
      Pigment A TiO2 particles produced minor inflammation at 24 hours postexposure and
      these effects were not significantly different from exposures to R-100 or
      carbonyl iron particles. Pigment A-exposed lung tissue sections appeared normal
      at 1 and 3 months postexposure. In contrast, pulmonary exposures to quartz
      particles in rats produced a dose-dependent lung inflammatory response
      characterized by neutrophils and foamy (lipid-containing) alveolar macrophage
      accumulation as well as evidence of early lung tissue thickening consistent with
      the development of pulmonary fibrosis. Based on our results, we conclude the
      following: 1) Pulmonary instillation exposures to Pigment A TiO2 particles at 5
      mg/kg produced a transient lung inflammatory response which was not different
      from the lung response to R-100 TiO2 particles or carbonyl iron particles; 2) the
      response to Pigment A was substantially less active in terms of inflammation,
      cytotoxicity, and fibrogenic effects than the positive control particle-type,
      quartz particles. Thus, based on the findings of this study, we would expect that
      inhaled Pigment A TiO2 particles would have a low risk potential for producing
      adverse pulmonary health effects.

PMID- 16438715
TI  - Evidence for conservation and selection of upstream open reading frames suggests
      probable encoding of bioactive peptides.
AB  - BACKGROUND: Approximately 40% of mammalian mRNA sequences contain AUG
      trinucleotides upstream of the main coding sequence, with a quarter of these AUGs
      demarcating open reading frames of 20 or more codons. In order to investigate
      whether these open reading frames may encode functional peptides, we have carried
      out a comparative genomic analysis of human and mouse mRNA 'untranslated regions'
      using sequences from the RefSeq mRNA sequence database. RESULTS: We have
      identified over 200 upstream open reading frames which are strongly conserved
      between the human and mouse genomes. Consensus sequences associated with
      efficient initiation of translation are overrepresented at the AUG trinucleotides
      of these upstream open reading frames, while comparative analysis of their DNA
      and putative peptide sequences shows evidence of purifying selection. CONCLUSION:
      The occurrence of a large number of conserved upstream open reading frames, in
      association with features consistent with protein translation, strongly suggests
      evolutionary maintenance of the coding sequence and indicates probable functional
      expression of the peptides encoded within these upstream open reading frames.

PMID- 16438716
TI  - Discovering semantic features in the literature: a foundation for building
      functional associations.
AB  - BACKGROUND: Experimental techniques such as DNA microarray, serial analysis of
      gene expression (SAGE) and mass spectrometry proteomics, among others, are
      generating large amounts of data related to genes and proteins at different
      levels. As in any other experimental approach, it is necessary to analyze these
      data in the context of previously known information about the biological entities
      under study. The literature is a particularly valuable source of information for
      experiment validation and interpretation. Therefore, the development of automated
      text mining tools to assist in such interpretation is one of the main challenges
      in current bioinformatics research. RESULTS: We present a method to create
      literature profiles for large sets of genes or proteins based on common semantic
      features extracted from a corpus of relevant documents. These profiles can be
      used to establish pair-wise similarities among genes, utilized in gene/protein
      classification or can be even combined with experimental measurements. Semantic
      features can be used by researchers to facilitate the understanding of the
      commonalities indicated by experimental results. Our approach is based on non
      negative matrix factorization (NMF), a machine-learning algorithm for data
      analysis, capable of identifying local patterns that characterize a subset of the
      data. The literature is thus used to establish putative relationships among
      subsets of genes or proteins and to provide coherent justification for this
      clustering into subsets. We demonstrate the utility of the method by applying it
      to two independent and vastly different sets of genes. CONCLUSION: The presented
      method can create literature profiles from documents relevant to sets of genes.
      The representation of genes as additive linear combinations of semantic features
      allows for the exploration of functional associations as well as for clustering,
      suggesting a valuable methodology for the validation and interpretation of high
      throughput experimental data.

PMID- 16438718
TI  - A case of absent right and persistent left superior vena cava.
AB  - BACKGROUND AND PURPOSE: Our case report deals with the importance of detailed
      echocardiographic examination for differential diagnosis of coronary sinus
      dilation and development of abnormalities of great thoracic veins. CASE
      PRESENTATION: A 49-year-old man underwent transthoracic echocardiography for
      atypical chest pain. A dilated coronary sinus was found and venous contrast
      echocardiography raised the suspicion of absent right and persistent left
      superior vena cava. Transesophageal echocardiography showed absence of right
      superior vena cava. The echocardiographic findings were confirmed by upper venous
      digital subtraction cavography. CONCLUSION: combination of agenesia of right SVC
      and isolated persistent left SVC in adult patients is a very rare abnormality.
      Both clinicians and sonographers should be alerted to the possible presence of
      this combined venous anomaly. Transthoracic echocardiograpy - including agitated
      saline infusion to the antecubital vein - is an important diagnostic tool for
      accurate diagnosis of this congenital thoracic venous malformation.

PMID- 16438717
TI  - Comparison of AIMS2-SF, WOMAC, x-ray and a global physician assessment in order
      to approach quality of life in patients suffering from osteoarthritis.
AB  - BACKGROUND: Chronic diseases like osteoarthritis (OA) substantially affect
      different dimensions of quality of life (QoL). The aim of the study was to reveal
      possible factors which mainly influence general practitioners (GPs) assessment of
      patients' QoL. METHODS: 220 primary care patients with OA of the knee or the hip
      treated by their general practitioner for at least one year were included. All
      GPs were asked to assess patients' QoL based on the patients' history, actual
      examination and existing x-rays by means of a visual analog scale (VAS scale),
      resulting in values ranging from 0 to 10. Patients were asked to complete the
      McMaster Universities Osteoarthritis Index (WOMAC) and the Arthritis Impact
      Measurement Scale2 Short Form (AIMS2-SF) questionnaire. RESULTS: Significant
      correlations were revealed between "GP assessment" and the AIMS2-SF scales
      "physical" (rho = 0.495) and "symptom" (rho = 0.598) as well as to the "pain"
      scale of the WOMAC (rho = 0.557). A multivariate ordinal regression analysis
      revealed only the AIMS2-SF "symptom" scale (coefficient beta = 0.2588; p =
      0.0267) and the x-ray grading according to Kellgren and Lawrence as significant
      influence variables (beta = 0.6395; p = 0.0004). CONCLUSION: The results of the
      present study suggest that physicians' assessment of patients' QoL is mainly
      dominated by physical factors, namely pain and severity of x-ray findings. Our
      results suggest that socioeconomic and psychosocial factors, which are known to
      have substantial impact on QoL, are underestimated or missed. Moreover, the
      overestimation of x-ray findings, which are known to be less correlated to QoL,
      may cause over-treatment while important and promising targets to increase
      patients' QoL are missed.

PMID- 16438719
TI  - Sequential events of apoptosis involving docetaxel, a microtubule-interfering
      agent: a cytometric study.
AB  - BACKGROUND: Despite the great advances in the understanding of programmed cell
      death, little attention has been paid to the sequence of the events that
      characterise it. In particular, the course of apoptotic events induced by
      microtubule-interfering agents such as taxanes is poorly understood. In order to
      increase such knowledge, we studied a number of independent biochemical and
      cytological modifications using cytometric methods in a bladder cancer cell line
      treated with the second generation taxane, docetaxel. RESULTS: Within a few
      hours, drug treatment had induced mitochondrial membrane transition, cell
      shrinkage and a decrease in granularity. Cell cycle was almost completely blocked
      in G2/M phase within 24 hours. The hypodiploid peak started to become prominent
      48 hours after the treatment. At the same time, the appearance of a DNA ladder
      demonstrated caspase-dependent chromatin fragmentation. Concurrently, specific
      cell surface modifications took place, involving at first glycoprotein
      syalilation and later phospholipid asymmetry. DNA fragmentation was subsequently
      detected by TUNEL assay. Over time, cell membranes became permeable to propidium
      iodide. A very similar time-course of apoptotic events was found after treatment
      of a myelomonocytic cell line with the same drug. CONCLUSION: After discussing
      some characteristics of the methods employed and their limitations, a succession
      of apoptotic events over time is suggested, in which the collapse of
      mitochondrial transmembrane potential (Deltapsim) is the earliest sign of
      apoptosis.

PMID- 16438720
TI  - Left ventricular free wall impeding rupture in post-myocardial infarction period
      diagnosed by myocardial contrast echocardiography: case report.
AB  - BACKGROUND: Left ventricular free wall rupture occurs in up to 10% of the in
      hospital deaths following myocardial infarction. It is mainly associated with
      posterolateral myocardial infarction and its antemortem diagnosis is rarely made.
      Contrast echocardiography has been increasingly used for the evaluation of
      myocardial perfusion in patients with acute myocardial infarction, with important
      prognostic implications. In this case, we reported its use for the detection of a
      mechanical complication following myocardial infarction. CASE PRESENTATION: A 50
      year-old man with acute myocardial infarction in the lateral wall underwent
      myocardial contrast echocardiography for the evaluation of myocardial perfusion
      in the third day post-infarction. A perfusion defect was detected in lateral and
      inferior walls as well as the presence of contrast extrusion from the left
      ventricular cavity into the myocardium, forming a serpiginous duct extending from
      the endocardium to the epicardial region of the lateral wall, without
      communication with the pericardial space. Magnetic resonance imaging confirmed
      the diagnosis of impending rupture of the left ventricular free wall. While
      waiting for cardiac surgery, patient presented with cardiogenic shock and died.
      Anatomopathological findings were consistent with acute myocardial infarction in
      the lateral wall and a left ventricular free wall rupture at the infarct site.
      CONCLUSION: This case illustrates the early diagnosis of left ventricular free
      wall rupture by contrast echocardiography. Due to its ability to be performed at
      bedside this modality of imaging has the potential to identify this catastrophic
      condition in patients with acute myocardial infarction and help to treat these
      patients with emergent surgery.

PMID- 16438721
TI  - SynTReN: a generator of synthetic gene expression data for design and analysis of
      structure learning algorithms.
AB  - BACKGROUND: The development of algorithms to infer the structure of gene
      regulatory networks based on expression data is an important subject in
      bioinformatics research. Validation of these algorithms requires benchmark data
      sets for which the underlying network is known. Since experimental data sets of
      the appropriate size and design are usually not available, there is a clear need
      to generate well-characterized synthetic data sets that allow thorough testing of
      learning algorithms in a fast and reproducible manner. RESULTS: In this paper we
      describe a network generator that creates synthetic transcriptional regulatory
      networks and produces simulated gene expression data that approximates
      experimental data. Network topologies are generated by selecting subnetworks from
      previously described regulatory networks. Interaction kinetics are modeled by
      equations based on Michaelis-Menten and Hill kinetics. Our results show that the
      statistical properties of these topologies more closely approximate those of
      genuine biological networks than do those of different types of random graph
      models. Several user-definable parameters adjust the complexity of the resulting
      data set with respect to the structure learning algorithms. CONCLUSION: This
      network generation technique offers a valid alternative to existing methods. The
      topological characteristics of the generated networks more closely resemble the
      characteristics of real transcriptional networks. Simulation of the network
      scales well to large networks. The generator models different types of biological
      interactions and produces biologically plausible synthetic gene expression data.

PMID- 16438722
TI  - Determinants of mortality for adults with cystic fibrosis admitted in Intensive
      Care Unit: a multicenter study.
AB  - BACKGROUND: Intensive care unit (ICU) admission of adults with cystic fibrosis
      (CF) is controversial because of poor outcome. This appraisal needs re-evaluation
      following recent changes in both CF management and ICU daily practice. Objectives
      were to determine long-term outcome of adults with CF admitted in ICU and to
      identify prognostic factors. METHODS: Retrospective multicenter study of 60 ICU
      hospitalizations for 42 adult CF patients admitted between 2000 and 2003. Reason
      for ICU admission, ventilatory support provided and one-year survival were
      recorded. Multiple logistic analysis was used to determine predictors of
      mortality. RESULTS: Prior to ICU admission, all patients (mean age 28.1 +/- 8 yr)
      had a severe lung disease (mean FEV1 28 +/- 12% predicted; mean PaCO2 47 +/- 9
      mmHg). Main reason for ICU hospitalization was pulmonary infective exacerbation
      (40/60). At admission, noninvasive ventilation was used in 57% of cases and was
      successful in 67% of patients. Endotracheal intubation was implemented in 19
      episodes. Overall ICU mortality rate was 14%. One year after ICU discharge, 10 of
      the 28 survivors have been lung transplanted. Among recognized markers of CF
      disease severity, only the annual FEV1 loss was associated with a poor outcome
      (HR = 1.47 [1.18-1.85], p = 0.001). SAPSII (HR = 1.08 [1.03-1.12], p < 0.001) and
      endotracheal intubation (HR = 16.60 [4.35-63.34], p < 0.001) were identified as
      strong independent predictors of mortality. CONCLUSION: Despite advanced lung
      disease, adult patients with CF admitted in ICU have high survival rate.
      Endotracheal intubation is associated with a poor prognosis and should be used as
      the last alternative. Although efforts have to be made in selecting patients with
      CF likely to benefit from ICU resources, ICU admission of these patients should
      be considered.

PMID- 16438723
TI  - MassSorter: a tool for administrating and analyzing data from mass spectrometry
      experiments on proteins with known amino acid sequences.
AB  - BACKGROUND: Proteomics is the study of the proteome, and is critical to the
      understanding of cellular processes. Two central and related tasks of proteomics
      are protein identification and protein characterization. Many small laboratories
      are interested in the characterization of a small number of proteins, e.g., how
      posttranslational modifications change under different conditions. RESULTS: We
      have developed a software tool called MassSorter for administrating and analyzing
      data from peptide mass fingerprinting experiments on proteins with known amino
      acid sequences. It is meant for small scale mass spectrometry laboratories that
      are interested in posttranslational modifications of known proteins. Several
      experiments can be compared simultaneously, and the matched and unmatched peak
      values are clearly indicated. The hits can be sorted according to m/z values
      (default) or according to the sequence of the protein. Filters defined by the
      user can mark autolytic protease peaks and other contaminating peaks (keratins,
      proteins co-migrating with the protein of interest, etc.). Unmatched peaks can be
      further analyzed for unexpected modifications by searches against a local version
      of the UniMod database. They can also be analyzed for unexpected cleavages, a
      highly useful feature for proteins that undergo maturation by proteolytic
      cleavage, creating new N- or C-terminals. Additional tools exist for
      visualization of the results, like sequence coverage, accuracy plots, different
      types of statistics, 3D models, etc. The program and a tutorial are freely
      available for academic users at http://www.bioinfo.no/software/massSorter.
      CONCLUSION: MassSorter has a number of useful features that can promote the
      analysis and administration of MS-data.

PMID- 16438724
TI  - Smad4-expression is decreased in breast cancer tissues: a retrospective study.
AB  - BACKGROUND: Although transforming growth factor beta (TGF-beta) typically
      inhibits proliferation of epithelial cells, consistent with a tumor suppressor
      activity, it paradoxically also exhibits pro-metastatic activity in the later
      stages of carcinogenesis. Since tumors often display altered TGF-beta signaling,
      particularly involving the Smad-pathway, we investigated the role of Smad4
      expression in breast cancer. METHODS: Smad4 expression was investigated by
      immunohistochemistry in formalin-fixed, paraffin-embedded tissue from 197 samples
      of primary breast cancer obtained between 1986 and 1998. The prognostic value of
      Smad4-expression was analyzed. RESULTS: Smad4 expression was found to be reduced
      in lobular and ductal breast carcinoma as compared to surrounding uninvolved
      lobular and ductal breast epithelia (p < 0.001, n = 50). Smad4-expression
      correlated positively with expression of TGF-beta-receptor I (p < 0.001, n = 197)
      and TGF-beta-receptor II (p < 0.001, n = 197), but showed no significant
      correlation with tumor size, metastases, nodal status, histological grade,
      histological type, or estrogen receptor expression. While not achieving
      statistical significance, there was a trend towards longer survival times in
      patients with Smad4 negative tumors. CONCLUSION: According to the suggested role
      of Smad4 as a tumor suppressor we observed that expression of Smad4 is lower in
      human breast cancer than in surrounding breast epithelium. However, we also
      observed a trend towards longer survival times in Smad4-negative patients,
      indicating the complex role of TGF-beta signaling in tumor progression.

PMID- 16438725
TI  - Influence of postpartum onset on the course of mood disorders.
AB  - BACKGROUND: To ascertain the impact of postpartum onset (PPO) on the subsequent
      time course of mood disorders. METHODS: This retrospective study compared per
      year rates of excited (manic or mixed) and depressive episodes between fifty-five
      women with bipolar (N = 22) or major depressive (N = 33) disorders with first
      episode occurring postpartum (within four weeks after childbirth according to DSM
      IV definition) and 218 non-postpartum onset (NPPO) controls. Such patients had a
      traceable illness course consisting of one or more episodes alternating with
      complete symptom remission and no additional diagnoses of axis I disorders,
      mental retardation or brain organic diseases. A number of variables reported to
      influence the course of mood disorders were controlled for as possible
      confounding factors RESULTS: Bipolar women with postpartum onset disorder had
      fewer excited episodes (p = 0.005) and fewer episodes of both polarities (p =
      0.005) compared to non-postpartum onset subjects. No differences emerged in the
      rates of depressive episodes. All patients who met criteria for rapid cycling
      bipolar disorder (7 out of 123) were in the NPPO group. Among major depressives,
      PPO patients experienced fewer episodes (p = 0.016). With respect to clinical and
      treatment features, PPO-MDD subjects had less personality disorder comorbidity (p
      = 0.023) and were less likely to be on maintenance treatment compared to NPPO
      comparison subjects (p = 0.002) CONCLUSION: Such preliminary findings suggest
      that PPO mood disorders may be characterized by a less recurrent time course.
      Future research in this field should elucidate the role of comorbid personality
      disorders and treatment. Moreover it should clarify whether PPO disorders are
      also associated with a more positive outcome in terms of social functioning and
      quality of life.

PMID- 16438726
TI  - Visual fields in patients who have undergone vitrectomy for complications of
      diabetic retinopathy. A prospective study.
AB  - BACKGROUND: To determine the extent of visual field loss in patients who had
      required a pars plana vitrectomy secondary to complications of proliferative
      diabetic retinopathy. METHODS: Patients that had undergone a vitrectomy on at
      least one eye for treatment of either vitreous haemorrhage or tractional retinal
      detachment were selected for study. ETDRS acuity and Humphrey binocular Esterman
      visual field testing were performed and compared to the minimum standards for
      safe driving as defined by the Royal College of Ophthalmologists in 1999. In
      addition to this Goldman kinetic visual fields using a III4e and V4e stimulus
      size and central 24-2 threshold test with the SITA-fast strategy were performed
      on the vitrectomised eye. RESULTS: 20 patients (n = 20) were recruited. Mean
      visual acuity in the eye being tested was 0.20 (Snellen 6/9.5). Results from the
      Humphrey field analyzer showed a mean number of abnormal stimulus locations of
      71.2% (p < 0.005). 70% of patients had sufficient binocular acuity to drive and
      of these 71.4% were shown not to have a minimum visual field for safe driving on
      binocular Esterman field analysis. CONCLUSION: Vitrectomy potentially allows
      retention/restoration of good visual acuity in patients with complications of
      proliferative diabetic retinopathy. However patients may be suffering from
      unrecognized visual impairment consequent upon extensive visual field loss which
      in over two thirds of patients may be sufficiently severe to preclude safe
      driving.

PMID- 16438727
TI  - All-cause and cardiovascular mortality among ethnic German immigrants from the
      Former Soviet Union: a cohort study.
AB  - BACKGROUND: Migration is a phenomenon of particular Public Health importance.
      Since 1990, almost 2 million ethnic Germans (Aussiedler) have migrated from the
      former Soviet Union (FSU) to Germany. This study compares their overall and
      cardiovascular disease (CVD) mortality to that of Germany's general population.
      Because of high overall and CVD mortality in the FSU and low socio-economic
      status of Aussiedler in Germany, we hypothesize that their mortality is higher.
      METHODS: We conducted a retrospective cohort study for 1990-2002 with data of
      34,393 Aussiedler. We assessed vital status at population registries and causes
      of death at the state statistical office. We calculated standardized mortality
      ratios (SMRs) for the whole cohort and substrata of covariables such as age, sex
      and family size. To assess multivariate effects, we used Poisson regression.
      RESULTS: 1657 cohort members died before December 31, 2002, and 680 deaths
      (41.03%) were due to CVD. The SMR for the whole cohort was 0.85 (95%-CI 0.81
      0.89) for all causes of death and 0.79 (95%-CI 0.73-0.85) for CVD. SMRs were
      higher than one for younger Aussiedler and lower for older ones. There was no
      clear effect of duration of stay on SMRs. For 1990-93, SMRs were significantly
      lower than in subsequent years. In families comprising at least five members upon
      arrival in Germany, SMRs were significantly lower than in smaller families.
      CONCLUSION: In contrast to our hypothesis on migrants' health, overall and CVD
      mortality among Aussiedler is lower than in Germany's general population.
      Possible explanations are a substantially better health status of Aussiedler in
      the FSU as compared to the local average, a higher perceived socio-economic
      status of Aussiedler in Germany, or selection effects. SMR differences between
      substrata need further exploration, and risk factor data are needed.

PMID- 16438728
TI  - Sperm protein 17 is expressed in human nervous system tumours.
AB  - BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was
      originally isolated from a rabbit epididymal sperm membrane and testis membrane
      pellet. It has recently been included in the cancer/testis (CT) antigen family,
      and shown to be expressed in multiple myeloma and ovarian cancer. We investigated
      its immunolocalisation in specimens of nervous system (NS) malignancies, in order
      to establish its usefulness as a target for tumour-vaccine strategies. METHODS:
      The expression of Sp17 was assessed by means of a standardised
      immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and
      paraffin embedded surgical specimens of NS malignancies, including 28
      neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5
      oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral
      nerve sheath tumours (4 schwannomas, and 1 neurofibroma). RESULTS: A number of
      neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously
      immunopositive for Sp17. None of the peripheral nerve sheath tumours was
      immunopositive for Sp17. The expression pattern was heterogeneous in all of the
      positive samples, and did not correlate with the degree of malignancy.
      CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17
      suggest that it cannot be used as a unique immunotherapeutic target in NS cancer.
      However, our results do show the immunolocalisation of Sp17 in a proportion of NS
      tumour cells, but not in their non-pathological counterparts. The emerging
      complex function of Sp17 makes further studies necessary to clarify the link
      between it and immunopositive cells.

PMID- 16438729
TI  - Sex and age specific effects of chromosomal regions linked to body mass index in
      the Framingham Study.
AB  - BACKGROUND: Previously, we reported significant linkage of body mass index (BMI)
      to chromosomes 6 and 11 across six examinations, covering 28 years, of the
      Framingham Heart Study. These results were on all individuals available at each
      exam, thus the sample size varied from exam to exam. To remove any effect of
      sample size variation we have now constructed six subsets; for each exam
      individuals were only included if they were measured at every exam, i.e. for each
      exam, included individuals comprise the intersection of the original six exams.
      This strategy preferentially removed older individuals who died before reaching
      the sixth exam, thus the intersection datasets are smaller (n = 1114) and
      significantly younger than the full datasets. We performed variance components
      linkage analysis on these intersection datasets and on their sex-specific
      subsets. RESULTS: Results from the sex-specific genome scans revealed 11 regions
      in which a sex-specific maximum lodscore was at least 2.0 for at least one
      dataset. Randomization tests indicated that all 11 regions had significant (p <
      0.05) differences in sex-specific maximum lodscores for at least three datasets.
      The strongest sex-specific linkage was for men on chromosome 16 with maximum
      lodscores 2.70, 3.00, 3.42, 3.61, 2.56 and 1.93 for datasets 1-6 respectively.
      Results from the full genome scans revealed that linked regions on chromosomes 6
      and 11 remained significantly and consistently linked in the intersection
      datasets. Surprisingly, the maximum lodscore on chromosome 10 for dataset 1
      increased from 0.97 in the older original dataset to 4.23 in the younger smaller
      intersection dataset. This difference in maximum lodscores was highly significant
      (p < 0.0001), implying that the effect of this chromosome may vary with age. Age
      effects may also exist for the linked regions on chromosomes 6 and 11.
      CONCLUSION: Sex specific effects of chromosomal regions on BMI are common in the
      Framingham study. Some evidence also exists for age-specific effects of
      chromosomal regions.

PMID- 16438730
TI  - An improved distance measure between the expression profiles linking co
      expression and co-regulation in mouse.
AB  - BACKGROUND: Many statistical algorithms combine microarray expression data and
      genome sequence data to identify transcription factor binding motifs in the low
      eukaryotic genomes. Finding cis-regulatory elements in higher eukaryote genomes,
      however, remains a challenge, as searching in the promoter regions of genes with
      similar expression patterns often fails. The difficulty is partially attributable
      to the poor performance of the similarity measures for comparing expression
      profiles. The widely accepted measures are inadequate for distinguishing genes
      transcribed from distinct regulatory mechanisms in the complicated genomes of
      higher eukaryotes. RESULTS: By defining the regulatory similarity between a gene
      pair as the number of common known transcription factor binding motifs in the
      promoter regions, we compared the performance of several expression distance
      measures on seven mouse expression data sets. We propose a new distance measure
      that accounts for both the linear trends and fold-changes of expression across
      the samples. CONCLUSION: The study reveals that the proposed distance measure for
      comparing expression profiles enables us to identify genes with large number of
      common regulatory elements because it reflects the inherent regulatory
      information better than widely accepted distance measures such as the Pearson's
      correlation or cosine correlation with or without log transformation.

PMID- 16438731
TI  - Perforated peptic duodenal ulcer in a paraesophageal hernia--a case report of a
      rare surgical emergency.
AB  - BACKGROUND: Paraesophageal hernias are quite common and sometimes feared due to
      the risk of incarceration and strangulation of any herniated organ. The hereby
      reported combination of an incarcerated paraesophageal hernia containing a
      perforated peptic ulcer is extremely rare. CASE PRESENTATION: An elderly man with
      multiple medical conditions was admitted due to severe upper abdominal pain. The
      patient was found to have a paraesophageal hernia and underwent a laparotomy. In
      the hernia, a perforated benign peptic duodenal ulcer was found. The duodenal
      defect was over-sewn, the hernial defect was closed and the former hernial cavity
      was drained by a right-sided chest tube. The patient was discharged one month
      after surgery and was found to do well at follow-up one month after discharge.
      CONCLUSION: This is the first report of a patient surviving the extremely rare
      and life-threatening combination of a perforated peptic duodenal ulcer in a
      paraesophageal hernia.

PMID- 16438733
TI  - Single- versus two- layer intestinal anastomosis: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: To compare single- with two- layer intestinal anastomosis after
      intestinal resection: a meta-analysis of randomized controlled trials. METHODS:
      Randomized controlled trials comparing single- with two-layer intestinal
      anastomosis were identified using a systematic search of Medline, Embase and the
      Cochrane Library Databases covering articles published from 1966 to 2004. Outcome
      of primary interest was postoperative leak. A risk ratio for trial outcomes and
      weighted pooled estimates for data were calculated. A fixed-effect model weighted
      using Mantel-Haenszel methods and a random-effect model using DerSimonian-Laird
      methods were employed. RESULTS: Six trials were analyzed, comprising 670
      participants (single-layer group, n = 299; two-layer group, n = 371). Data on
      leaks were available from all included studies. Combined risk ratio using
      DerSimonian-Laird methods was 0.91 (95% CI = 0.49 to 1.69), and indicated no
      significant difference. Inter-study heterogeneity was significant (chi2 = 10.5,
      d.f. = 5, p = 0.06). CONCLUSION: No evidence was found that two-layer intestinal
      anastomosis leads to fewer post-operative leaks than single layer. Considering
      duration of the anastomosis procedure and medical expenses, single-layer
      intestinal anastomosis appears to represent the optimal choice for most surgical
      situations.

PMID- 16438732
TI  - Wnt signalling in lung development and diseases.
AB  - There are several signalling pathways involved in lung organogenesis including
      Notch, TGFbeta/BMP, Sonic hedgehog (Shh), FGF, EGF, and Wnt. Despite the widely
      acknowledged significance of Wnt signalling in embryonic lung development, the
      role of different Wnt pathways in lung pathologies has been slow to emerge. In
      this review, we will present a synopsis of current Wnt research with particular
      attention paid to the role of Wnt signals in lung development and in pulmonary
      diseases.

PMID- 16438734
TI  - EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of
      TGF-beta signaling in lung fibroblasts.
AB  - BACKGROUND: Fourteen-membered ring macrolides have been effective in reducing
      chronic airway inflammation and also preventing lung injury and fibrosis in
      bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new
      derivative of erythromycin (EM) without the bactericidal effects. We investigated
      the anti-inflammatory and antifibrotic effects of EM703 in an experimental model
      of bleomycin-induced lung injury and subsequent fibrosis in mice. METHODS: Seven
      week-old male ICR mice were used. All experiments used eight mice/group, unless
      otherwise noted in the figure legends. Bleomycin was administered intravenously
      to the mice on day 0. EM703 was orally administered daily to mice. All groups
      were examined for cell populations in the bronchoalveolar lavage (BAL) fluid and
      for induction of messenger RNA (mRNA) of Smad3 and Smad4 in the lung tissues by
      reverse transcriptase (RT)-polymerase chainreaction (PCR) on day 7. Fibroblastic
      foci were assessed histologically, and the hydroxyproline content was chemically
      determined in the lung tissues on day 28. We performed assay of proliferation and
      soluble collagen production, and examined the induction of mRNA of Smad3 and
      Smad4 by RT-PCR in murine lung fibroblast cell line MLg2908. We also examined
      Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3) protein assay by western
      blotting in MLg2908. RESULTS: Bleomycin-induced lung fibrosis, and the
      infiltration of macrophages and neutrophils into the airspace were inhibited by
      EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by
      bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast
      proliferation and the collagen production in lung fibroblasts induced by
      Transforming growth factor-beta (TGF-beta). The expression of Smad3 and Smad4
      mRNA in murine lung fibroblasts disappeared due to TGF-beta, but was recovered by
      EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine
      lung fibroblasts induced by TGF-beta. CONCLUSION: These findings suggest that
      EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti
      inflammation and regulation of TGF-beta signaling in lung fibroblasts.

PMID- 16438735
TI  - Municipal distribution of bladder cancer mortality in Spain: possible role of
      mining and industry.
AB  - BACKGROUND: Spain shows the highest bladder cancer incidence rates in men among
      European countries. The most important risk factors are tobacco smoking and
      occupational exposure to a range of different chemical substances, such as
      aromatic amines. METHODS: This paper describes the municipal distribution of
      bladder cancer mortality and attempts to "adjust" this spatial pattern for the
      prevalence of smokers, using the autoregressive spatial model proposed by Besag,
      York and Mollie, with relative risk of lung cancer mortality as a surrogate.
      RESULTS: It has been possible to compile and ascertain the posterior distribution
      of relative risk for bladder cancer adjusted for lung cancer mortality, on the
      basis of a single Bayesian spatial model covering all of Spain's 8077 towns. Maps
      were plotted depicting smoothed relative risk (RR) estimates, and the
      distribution of the posterior probability of RR>1 by sex. Towns that registered
      the highest relative risks for both sexes were mostly located in the Provinces of
      Cadiz, Seville, Huelva, Barcelona and Almeria. The highest-risk area in Barcelona
      Province corresponded to very specific municipal areas in the Bages district,
      e.g., Suria, Sallent, Balsareny, Manresa and Cardona. CONCLUSION:
      Mining/industrial pollution and the risk entailed in certain occupational
      exposures could in part be dictating the pattern of municipal bladder cancer
      mortality in Spain. Population exposure to arsenic is a matter that calls for
      attention. It would be of great interest if the relationship between the chemical
      quality of drinking water and the frequency of bladder cancer could be studied.

PMID- 16438736
TI  - Hypoxia-inducible transcription factor-1alpha promotes hypoxia-induced A549
      apoptosis via a mechanism that involves the glycolysis pathway.
AB  - BACKGROUND: Hypoxia-inducible transcription factor-1alpha (HIF-1alpha), which
      plays an important role in controlling the hypoxia-induced glycolysis pathway, is
      a "master" gene in the tissue hypoxia response during tumor development. However,
      its role in the apoptosis of non-small cell lung cancer remains unknown. Here, we
      have studied the effects of HIF-1alpha on apoptosis by modulating HIF-1alpha gene
      expression in A549 cells through both siRNA knock-down and over-expression.
      METHODS: A549 cells were transfected with a HIF-1alpha siRNA plasmid or a HIF
      1alpha expression vector. Transfected cells were exposed to a normoxic or hypoxic
      environment in the presence or absence of 25 mM HEPES and 2-deoxyglucose (2-DG)
      (5 mM). The expression of three key genes of the glycolysis pathway, glucose
      transporter type 1(GLUT1), phosphoglycerate kinase 1(PGK1), and hexokinase
      1(HK1), were measured using real-time RT-PCR. Glycolysis was monitored by
      measuring changes of pH and lactate concentration in the culture medium.
      Apoptosis was detected by TUNEL assay and flow cytometry. RESULTS: Knocking down
      expression of HIF-1alpha inhibited the glycolysis pathway, increased the pH of
      the culture medium, and protected the cells from hypoxia-induced apoptosis. In
      contrast, over-expression of HIF-1alpha accelerated glycolysis in A549 cells,
      decreased the pH of the culture medium, and enhanced hypoxia-induced apoptosis.
      These effects of HIF-1alpha on glycolysis, pH of the medium, and apoptosis were
      reversed by treatment with the glycolytic inhibitor, 2-DG. Apoptosis induced by
      HIF-1alpha over-expression was partially inhibited by increasing the buffering
      capacity of the culture medium by adding HEPES. CONCLUSION: During hypoxia in
      A549 cells, HIF-1alpha promotes activity of the glycolysis pathway and decreases
      the pH of the culture medium, resulting in increased cellular apoptosis.

PMID- 16438737
TI  - Complete mitochondrial genome sequences for Crown-of-thorns starfish Acanthaster
      planci and Acanthaster brevispinus.
AB  - BACKGROUND: The crown-of-thorns starfish, Acanthaster planci (L.), has been
      blamed for coral mortality in a large number of coral reef systems situated in
      the Indo-Pacific region. Because of its high fecundity and the long duration of
      the pelagic larval stage, the mechanism of outbreaks may be related to its meta
      population dynamics, which should be examined by larval sampling and population
      genetic analysis. However, A. planci larvae have undistinguished morphological
      features compared with other asteroid larvae, hence it has been difficult to
      discriminate A. planci larvae in plankton samples without species-specific
      markers. Also, no tools are available to reveal the dispersal pathway of A.
      planci larvae. Therefore the development of highly polymorphic genetic markers
      has the potential to overcome these difficulties. To obtain genomic information
      for these purposes, the complete nucleotide sequences of the mitochondrial genome
      of A. planci and its putative sibling species, A. brevispinus were determined and
      their characteristics discussed. RESULTS: The complete mtDNA of A. planci and A.
      brevispinus are 16,234 bp and 16,254 bp in size, respectively. These values fall
      within the length variation range reported for other metazoan mitochondrial
      genomes. They contain 13 proteins, 2 rRNA, and 22 tRNA genes and the putative
      control region in the same order as the asteroid, Asterina pectinifera. The A + T
      contents of A. planci and A. brevispinus on their L strands that encode the
      majority of protein-coding genes are 56.3% and 56.4% respectively and are lower
      than that of A. pectinifera (61.2%). The percent similarity of nucleotide
      sequences between A. planci and A. brevispinus is found to be highest in the CO2
      and CO3 regions (both 90.6%) and lowest in ND2 gene (84.2%) among the 13 protein
      coding genes. In the deduced putative amino acid sequences, CO1 is highly
      conserved (99.2%), and ATP8 apparently evolves faster any of the other protein
      coding gene (85.2%). CONCLUSION: The gene arrangement, base composition, codon
      usage and tRNA structure of A. planci are similar to those of A. brevispinus.
      However, there are significant variations between A. planci and A. brevispinus.
      Complete mtDNA sequences are useful for the study of phylogeny, larval detection
      and population genetics.

PMID- 16438738
TI  - Restoration of diaphragmatic function after diaphragm reinnervation by inferior
      laryngeal nerve; experimental study in rabbits.
AB  - OBJECTIVES: To assess the possibilities of reinnervation in a paralyzed
      hemidiaphragm via an anastomosis between phrenic nerve and inferior laryngeal
      nerve in rabbits. Reinnervation of a paralyzed diaphragm could be an alternative
      to treat patients with ventilatory insufficiency due to upper cervical spine
      injuries. MATERIAL AND METHOD: Rabbits were divided into five groups of seven
      rabbits each. Groups I and II were respectively the healthy and the denervated
      control groups. The 3 other groups were all reinnervated using three different
      surgical procedures. In groups III and IV, phrenic nerve was respectively
      anastomosed with the abductor branch of the inferior laryngeal nerve and with the
      trunk of the inferior laryngeal nerve. In group V, the fifth and fourth cervical
      roots were respectively anastomosed with the abductor branch of the inferior
      laryngeal nerve and with the nerve of the sternothyroid muscle (originating from
      the hypoglossal nerve). Animals were evaluated 4 months later using
      electromyography, transdiaphragmatic pressure measurements, sonomicrometry and
      histological examination. RESULTS: A poor inspiratory activity was found in quiet
      breathing in the reinnervated groups, with an increasing pattern of activity
      during effort. In the reinnervated groups, transdiaphragmatic pressure
      measurements and sonomicrometry were higher in group III with no significant
      difference with groups IV and V. CONCLUSION: Inspiratory contractility of an
      hemidiaphragm could be restored with immediate anastomosis after phrenic nerve
      section between phrenic nerve and inferior laryngeal nerve.

PMID- 16438739
TI  - A prospective study of the transition rates of subthreshold (hypo)mania and
      depression in the general population.
AB  - BACKGROUND: Previous work suggests that subthreshold depression and subthreshold
      (hypo)mania are common, although little is known about the prognosis in terms of
      transition to clinical disorder. This paper presents data on the temporal
      relationship between subthreshold and clinical expression of mood phenotypes.
      METHOD: In a random general population sample of 7076 individuals, symptoms of
      depression and (hypo)mania were measured with the Composite International
      Diagnostic Interview (CIDI) at baseline, after 1 year, and 2 years later.
      RESULTS: At baseline, the lifetime prevalences of depressive and (hypo)manic
      symptoms were 17.2% and 1.2% respectively. Predictive values of mood symptoms for
      a DSM-III-R mood disorder ranged from 14.3% to 50%. (Hypo)manic mood symptoms had
      much higher predictive values than unipolar manifestations, not only for bipolar
      disorder but also for major depression. CONCLUSIONS: The subthreshold expressions
      of depression and (hypo)mania are prevalent and continuous with more severe
      clinical states. The cross-prediction of mood symptoms may support a continuum
      from depressive to (hypo)manic symptoms. The high predictive value of (hypo)manic
      symptoms for mood disorders suggests that the experience of (hypo)manic symptoms
      is a stronger indicator of vulnerability for mood dysregulation than the
      experience of depressive symptoms.

PMID- 16438740
TI  - Systematic review of multi-symptom conditions in Gulf War veterans.
AB  - BACKGROUND: Gulf War veterans have a number of health complaints. We therefore
      decided to carry out a systematic review to identify and summarize the findings
      from studies that have assessed multi-symptom conditions in Gulf War veterans and
      in an unexposed comparison group. METHOD: Studies published between January 1990
      and May 2004 were identified by searching a large number of electronic databases.
      Reference lists and websites were also searched and key researchers were
      contacted. Studies were included if they compared the prevalence of chronic
      fatigue syndrome, multiple chemical sensitivity, CDC-defined chronic multi
      symptom illness, fibromyalgia, or symptoms of either fatigue or numbness and
      tingling in Gulf War veterans and non-Gulf veterans. A total of 2401 abstracts
      were independently reviewed by two authors. RESULTS: Twenty-three publications
      fulfilled the inclusion criteria. Gulf deployment was most strongly associated
      with chronic fatigue syndrome (OR 3.8, 95% CI 2.2-6.7). Gulf War veterans were
      also approximately three and a half times more likely than non-Gulf veterans to
      report multiple chemical sensitivity or chronic multi-symptom illness as defined
      by CDC. The methodological quality of the studies varied but the later and larger
      studies were of a high methodological standard with robust sampling strategies,
      adequate response rates and good adjustment for confounders. CONCLUSIONS: The
      results support the hypothesis that deployment to the Gulf War is associated with
      greater reporting of multi-symptom conditions.

PMID- 16438741
TI  - Inter-identity amnesia in dissociative identity disorder: a simulated memory
      impairment?
AB  - BACKGROUND: Although included in the current edition of the DSM, there does not
      seem to be consensus among mental health professionals regarding the diagnostic
      status and scientific validity of dissociative identity disorder (DID). This
      study was aimed at the detection of simulation of inter-identity amnesia in DID.
      METHOD: A sample of 22 DID patients was included, together with a matched control
      sample of subjects instructed to simulate inter-identity amnesia, a guessor group
      that had no knowledge of the stimulus material and a normal control group. A
      multiple-choice recognition test was included. The rate of incorrect answers was
      determined. Moreover, the specific simulation strategy used was examined by
      providing subjects with a range of choices that varied in extent of disagreement
      with the correct answer and determining whether plausible or implausible answer
      alternatives were selected. RESULTS: On the recognition test DID patients
      selected incorrect answers above chance like simulators. Patients thus seem to
      use their knowledge of the correct answer in determining their given answer. They
      were not characterized by a well-thought-out simulating behaviour style, as
      indicated by the differences in selection of specific answer alternatives found
      between patients and simulators. CONCLUSIONS: DID patients were found not to be
      characterized by an actual memory retrieval inability, in contrast to their
      subjective reports. Instead, it is suggested that DID may more accurately be
      considered a disorder characterized by meta-memory problems, holding incorrect
      beliefs about their own memory functioning.

PMID- 16438742
TI  - Prevalence, subtypes, and correlates of DSM-IV conduct disorder in the National
      Comorbidity Survey Replication.
AB  - BACKGROUND: Prior research indicates that conduct disorder (CD) is associated
      with a range of co-morbid mental disorders. However, the actual prevalence,
      subtypes and patterns of co-morbidity of DSM-IV-defined CD in the general US
      population remains unknown. METHOD: Retrospective assessment of CD and other DSM
      IV disorders was conducted using fully structured diagnostic interviews among a
      nationally representative sample of respondents (n=3199) in the National
      Comorbidity Survey Replication (NCS-R). RESULTS: The estimated lifetime
      prevalence of CD in the US is 9.5% (12.0% among males and 7.1% among females),
      with a median age-of-onset of 11.6 (0.2) years. Latent class analysis (LCA)
      identified five CD subtypes characterized by rule violations, deceit/theft,
      aggression, severe covert behaviors, and pervasive CD symptoms. A dose-response
      relationship was revealed between CD subtype severity and risk of subsequent
      disorders. Results also indicated that CD typically precedes mood and substance
      use disorders, but most often occurs after impulse control and anxiety disorders.
      Although both active and remitted CD is associated with increased risk of the
      subsequent first onset of other mental disorders, remitted CD is associated with
      significantly lower risk of subsequent disorders. CONCLUSIONS: CD is prevalent
      and heterogeneous in the US population, and more severe subtypes and the presence
      of active CD are associated with higher risk of co-morbid disorders. Future
      prospective studies using general population samples will further inform the
      nature and course of this disorder.

PMID- 16438743
TI  - Exploring the time to intervene with a reactive mass vaccination campaign in
      measles epidemics.
AB  - The current WHO policy during measles outbreaks focuses on case management rather
      than reactive vaccination campaigns in urban areas of resource-poor countries
      having low vaccine coverage. Vaccination campaigns may be costly, or not timely
      enough to impact significantly on morbidity and mortality. We explored the time
      available for intervention during two recent epidemics. Our analysis suggests
      that the spread of measles in African urban settings may not be as fast as
      expected. Examining measles epidemic spread in Kinshasa (DRC), and Niamey (Niger)
      reveals a progression of smaller epidemics. Intervening with a mass campaign or
      in areas where cases have not yet been reported could slow the epidemic spread.
      The results of this preliminary analysis illustrate the importance of revisiting
      outbreak response plans.

PMID- 16438744
TI  - A stastistical system for detecting Salmonella outbreaks in British livestock.
AB  - Worldwide, early detection systems have been used in public health to aid the
      timely detection of increases in disease reporting that may be indicative of an
      outbreak. To date, their application to animal surveillance has been limited and
      statistical methods to analyse human health data have not been viewed as being
      applicable for animal health surveillance data. This issue was investigated by
      developing an early detection system for Salmonella disease in British livestock.
      We conclude that an early detection system, as for public health surveillance,
      can be an effective tool for enhanced surveillance. In order to implement this
      system in the future and extend it for other data types, we provide
      recommendations for improving the current data collection process. These
      recommendations will ensure that quality surveillance data are collected and used
      effectively to monitor disease in livestock populations.

PMID- 16438745
TI  - Relationship between Escherichia coli strains causing urinary tract infection in
      women and the dominant faecal flora of the same hosts.
AB  - To clarify whether prevalence or special pathogenicity is more important in
      determining urinary tract infection (UTI) causation, we compared the biotype,
      phylogenetic group, and virulence genes of Escherichia coli urine strains from 11
      women with acute lower UTI with those of the host's dominant intestinal E. coli
      strain(s). Twenty-one unique E. coli clones were identified. For three women, the
      single faecal clone identified was also the host's urine clone, whereas for eight
      women faecal samples yielded 1 or 2 distinct non-urine clones (total, n = 10),
      either with (n = 3) or without (n = 5) the concurrent urine clone. The eight
      urine clones from the latter eight women exhibited significantly greater inferred
      virulence, according to virulence gene content and phylogenetic background, than
      did the hosts' 10 corresponding 'faecal only' clones. In contrast, the three
      urine clones that were detected as the host's sole faecal clone exhibited
      significantly lower inferred virulence than the other eight urine clones, and
      were statistically indistinguishable from the 10 'faecal only' clones. In
      conclusion, special pathogenicity is an important determinant of UTI pathogenesis
      in women, although prevalence may occasionally allow less virulent strains to
      cause UTI.

PMID- 16438746
TI  - Molecular characteristics of Shigella spp. isolated from patients with diarrhoea
      in a new industrialized area of Thailand.
AB  - In this study, we used plasmid profile analysis, XbaI macrorestriction with
      pulsed-field gel electrophoresis (PFGE), and PCR of the ipaH gene, to study the
      molecular characteristics of 183 Shigella spp. isolated during May 2000 to April
      2003 from rectal swabs of patients with watery and/or bloody diarrhoea in a new
      industrialized area of Thailand. Among the 183 isolates, 167 were S. sonnei and
      16 were S. flexneri. For plasmid profile analysis, the 183 isolates revealed 16
      different plasmid patterns, designated patterns A to P. The sizes of the plasmid
      bands were: 6, 5.5, 5, 4.5, 4, 3.25, 2.75, 2.5, 2, 1.75, 1.5 and/or 1.25 kb. The
      frequency of each plasmid band was 4.5 kb (165 isolates), 3.25 kb (161 isolates),
      5.5 kb (129 isolates), 1.75 kb (121 isolates), 1.5 kb (35 isolates), 5 kb (21
      isolates), 2 kb (16 isolates), 2.75 kb (12 isolates), 1.25 kb (9 isolates), and 6
      kb (8 isolates). PFGE analysis revealed 45 different XbaI macrorestricted DNA
      banding patterns which could be grouped into 11 groups. All the isolates gave PCR
      amplicons of the ipaH gene. Plasmid profile analysis and PFGE are powerful tools
      for differentiation of the Shigella spp. This study provides important data on
      the molecular characteristics of Shigella isolates in Thailand, which could be
      useful as an epidemiological baseline for identifying relationships with strains
      that may emerge in the future.

PMID- 16438747
TI  - Sustained high levels of stored drinking water treatment and retention of hand
      washing knowledge in rural Kenyan households following a clinic-based
      intervention.
AB  - Nyanza Province, Kenya is characterized by poor water quality and high diarrhoea
      prevalence. To address these problems, nurses in a maternal and child health
      clinic in Homa Bay, Kenya were trained in household water chlorination with a
      locally available, social marketed product, and in six steps of proper hand
      washing. They were asked to communicate this information to their clients.
      Interviews immediately following the training by nurses were conducted on 220
      clients, of whom 168 (76%) reported being taught both procedures during their
      clinic visit. After 2 weeks, free chlorine residuals were present in stored
      drinking water in 67 out of 98 (68%) clients' homes and, 1 year later, in 36 out
      of 51 (71%) clients' homes. After 2 weeks, all six hand-washing steps were
      correctly demonstrated by 41 (44%) out of 93 clients, and by 17 out of 51 (34%) 1
      year later. This brief, practical intervention shows promise for vulnerable
      populations.

PMID- 16438748
TI  - Outbreak of hepatitis B in a nursing home associated with capillary blood
      sampling.
AB  - In 2001, two residents of a nursing home in Lower Saxony, Germany, were diagnosed
      with acute hepatitis B virus (HBV) infection. A systematic contact investigation
      of 188 residents yielded 19 confirmed or probable cases of acute or recent HBV
      infection and three persistent asymptomatic HBsAg carriers. Sequence analysis
      revealed that one carrier had high viraemia (109 genomes/ml), HBV genotype A2,
      and the same S gene and/or X gene sequence as 16 acutely infected persons. An
      unmatched case-control study was conducted with the 17 cases that had sequence
      identity together with 26 controls. The strongest association was found for
      treatment by a particular general practitioner (GP) (OR > 11, P < 0.001) and
      blood sampling for glucose monitoring on a particular day by the GP's staff (OR
      13.6, P < 0.001, adjusted OR 8.5, P = 0.017). Control measures were implemented.
      Serological controls after 6 and 18 months revealed that the outbreak was brought
      under control.

PMID- 16438749
TI  - Venous thromboembolism prevention in surgery and obstetrics: clinical practice
      guidelines.
AB  - BACKGROUND AND OBJECTIVE: To produce up-to-date clinical practice guidelines on
      the prevention of venous thromboembolism in surgery and obstetrics. METHODS: A
      Steering Committee defined the scope of the topic, the questions to be answered,
      and the assessment criteria. Eight multidisciplinary working groups (total of 70
      experts) performed a critical appraisal of the literature in the following
      disciplines: pharmacology of antithrombotic agents, orthopaedics; general surgery
      (gastrointestinal (GI) and varicose vein surgery); urology; gynaecology and
      obstetrics; thoracic, cardiac and vascular surgery; surgery of the head, neck and
      spine; and surgery of burns patients. The resultant reports and guidelines were
      submitted for comment and completion of the Appraisal of Guidelines Research &
      Evaluation questionnaire to a total of 150 peer reviewers, before producing
      definite guidelines. RESULTS: The report answers the following questions for each
      type of surgery: (i) What is the venous thromboembolism incidence according to
      clinical and/or paraclinical criteria in the absence of prophylaxis? (with
      stratification of venous thromboembolism risk into low, moderate and high
      categories); (ii) What is the efficacy and safety of the prophylactic measures
      used? (iii) When should prophylaxis be introduced and how long should it last?
      (iv) Does ambulatory surgery affect efficacy and safety of prophylaxis?
      CONCLUSIONS: Apart from answering the above questions, the guidelines provide a
      summary table for each discipline. This table stratifies types of surgery into
      the three risk categories, specifies the recommended prophylaxis for venous
      thromboembolism (pharmacological and/or mechanical) and grades each
      recommendation. In addition, whenever appropriate, the recommended prophylaxis is
      adjusted to low- and high-risk patients.

PMID- 16438750
TI  - How to inform a morbidly obese patient on the specific risk to develop
      postoperative pulmonary complications using evidence-based methodology.
AB  - BACKGROUND AND OBJECTIVE: Patients have the right to be informed about the
      expected benefits and risks of medical and surgical procedures. Ideally this
      information should be scientifically based and presented to the patient in time.
      In morbidly obese patient undergoing general anaesthesia, postoperative pulmonary
      complications are an important cause of postoperative morbidity and mortality. A
      46-yr-old female with a body mass index of 89.8 kg m(-2) was scheduled to undergo
      radical abdominal surgery for cervix carcinoma. In order to inform her accurately
      on the risk of developing postoperative pulmonary complications, we undertook to
      answer the following question: What is the risk to develop postoperative
      pulmonary complications in a morbidly obese patient about to undergo abdominal
      surgery under general anaesthesia? METHODS: A Medline search was conducted from
      1966 to 2004 with respect to postoperative pulmonary complications in abdominal
      surgery of morbidly obese patients. Altogether, 213 articles were found, of which
      seven were selected. Additionally, seven cross-references and or related articles
      were used. RESULTS: For obese patients who undergo abdominal surgery under
      general anaesthesia, the likelihood to develop atelectasis is 10.4 +/- 4.8% (P <
      0.001) with a correlation coefficient of 0.28-0.34 (P < 0.05). The likelihood to
      develop atelectasis and pneumonia taken together is 29.3% with an adjusted odds
      ratio of 2.82 (95% confidence interval 1.66-4.78; P = 0.0001). CONCLUSION:
      Considering the positive correlation coefficient and the high body mass index of
      this patient she has a risk of at least 29.3% to develop pneumonia and/or
      atelectasis, which should affect the anaesthetic strategy in this patient.

PMID- 16438751
TI  - Does preoperatively administered parecoxib prevent succinylcholine-associated
      myalgia? A randomized, placebo-controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Data from several studies implicate that pre-treatment
      with non-selective cyclooxygenase inhibitors such as aspirin or diclofenac may
      decrease the incidence of postoperative succinycholine-related myalgia. We tested
      the influence of a preoperatively administered selective cyclooxygenase 2
      inhibitor, parecoxib, on postoperative myalgia. METHODS: After Ethics Committee
      approval, 68 patients were randomized into two groups (n = 34 each). Group 1
      received parecoxib 40 mg intravenously 3 min before induction of anaesthesia, and
      Group 2 received saline (in a double-blinded manner). Incidence and severity of
      myalgia was evaluated systematically with a standardized questionnaire 24, 48 and
      72 h after anaesthesia. We also the assessed the number of patients who felt
      limited in their activity due to myalgia. RESULTS: Seven patients in the
      parecoxib-treated group complained of myalgia compared with 11 in the control
      group (not significant). No significant difference in the severity of myalgia or
      in the limitation of patients activity was found between the groups. CONCLUSION:
      Intravenous parecoxib 40 mg, when administered before induction of anaesthesia,
      did not reduce incidence and severity of postoperative myalgia and did not
      improve activity in those who suffered from myalgia.

PMID- 16438752
TI  - The correlation between the Richmond agitation-sedation scale and bispectral
      index during dexmedetomidine sedation.
AB  - BACKGROUND AND OBJECTIVES: The primary objective of sedation in the critically
      ill patient is to achieve security and comfort. The routine use of standardized
      and validated sedation scales and monitors are needed. The Richmond agitation
      sedation scale has been used but some patients cannot be evaluated with
      subjective assessment tools such as the Richmond agitation sedation scale because
      they lack motor responsiveness due to therapeutic paralysis or because they are
      receiving deep sedation. We aimed to assess the correlation of bispectral index
      with Richmond agitation sedation scale during dexmedetomidine sedation and
      evaluate the use of the bispectral index in monitoring the levels of sedation in
      intensive care patients. METHODS: This was a single centre, prospective, clinical
      study. Eleven mechanically-ventilated critically ill patients, aged 17-82 (50.09
      +/- 17.76; mean +/- SD) yr, 3 males and 8 females, APACHE II score 12.63 +/-
      3.90, SOFA score 3.27 +/- 1.73 were enrolled in the study. Patients received a
      dexmedetomidine infusion of 1 microg kg-1 over 10 min followed by a maintenance
      infusion of 0.5 microg kg-1 h-1 for 8 h. Sedation was assessed using the Richmond
      agitation sedation scale and bispectral index monitoring. Heart rate, blood
      pressure, respiratory rate and SPO2 were monitored. Wilcoxon signed rank sum test
      and Spearman's rank correlation analysis were used for statistical analysis.
      RESULTS: The variation of Richmond agitation sedation scale score was between 0.9
      and -1.7 bispectral index varied from 65 to 75. Significant correlations between
      Richmond agitation sedation scale and bispectral index values were found in this
      study. (r = 0.900; P = 0.0001) CONCLUSIONS: Richmond agitation sedation scale
      levels significantly correlated with bispectral index values during
      dexmedetomidine sedation in critically ill patients requiring mechanical
      ventilation in the intensive care unit.

PMID- 16438753
TI  - Preeclampsia: current understanding of the molecular basis of vascular
      dysfunction.
AB  - Preeclampsia is a pregnancy-specific disorder characterised by hypertension and
      proteinuria occurring after the 20th week of gestation. Delivery of the placenta
      results in resolution of the condition, implicating the placenta as a central
      culprit in the pathogenesis of preeclampsia. In preeclampsia, an inadequate
      placental trophoblast invasion of the maternal uterine spiral arteries results in
      poor placental perfusion, leading to placental ischaemia. This could result in
      release of factors into the maternal circulation that cause widespread activation
      or dysfunction of the maternal endothelium. Factors in the maternal circulation
      might induce oxidative stress and/or elicit an inflammatory response in the
      maternal endothelium, resulting in the altered expression of several genes
      involved in the regulation of vascular tone. This review addresses the potential
      circulating factors and the molecular mechanisms involved in the alteration of
      vascular function that occurs in preeclampsia.

PMID- 16438754
TI  - A survey on the knowledge and attitudes of anaesthesia providers in the United
      States of America, United Kingdom and Singapore on visual experiences during
      cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: To assess the knowledge, beliefs and attitudes of
      anaesthesia providers on the patients' possible intraoperative visual experiences
      during cataract surgery under local anaesthesia. METHODS: Anaesthesia providers
      from the Ophthalmic Anaesthesia Society (USA); British Ophthalmic Anaesthesia
      Society (UK); Alexandra Hospital, National University Hospital, Tan Tock Seng
      Hospital, Singapore General Hospital and Changi General Hospital (Singapore) were
      surveyed using a structured questionnaire. RESULTS: A total of 146
      anaesthesiologists (81.6%), 10 ophthalmologists (5.6%) and 23 nurse anaesthetists
      (12.8%) responded to the survey. Most respondents believed that patients would
      experience light perception and many also felt that patients might encounter
      other visual sensations such as movements, flashes, colours, surgical
      instruments, hands/fingers and the surgeon during the surgery. A significantly
      higher proportion of anaesthesia providers with previous experience of monitoring
      patients under topical anaesthesia believed that patients might experience the
      various visual sensations compared to those who have not previously monitored.
      For both topical and regional anaesthesia, anaesthesia providers who routinely
      counsel their patients are (1) more likely to believe that preoperative
      counselling helps or (2) were previously told by patients that they could see
      intraoperatively and/or that they were frightened by their visual sensations.
      These findings were statistically significant. CONCLUSIONS: The majority of
      anaesthesia providers in the USA, UK and Singapore are aware that patients may
      experience a variety of visual sensations during cataract surgery under regional
      or topical anaesthesia. Those who have previously managed patients undergoing
      cataract surgery under topical anaesthesia are more likely to believe this
      compared to those who have not.

PMID- 16438755
TI  - Subjective assessment of depth of anaesthesia by experienced and inexperienced
      anaesthetists.
AB  - BACKGROUND AND OBJECTIVE: To measure 'depth of anaesthesia', anaesthesiologists
      use a combination of observable end-points such as immobility and autonomic
      stability. Unconsciousness and amnesia are not reliably observable end-points,
      but correlate with parameters derived from the electroencephalogram. We
      investigated the association of subjective assessment and electroencephalographic
      measures of anaesthetic depth in a group of experienced (>4 yr of experience) and
      a group of inexperienced (<2 yr of experience) anaesthesiologists. METHODS: One
      hundred ASA I or II patients were assigned to either group. Anaesthesiologists
      assessed 'anaesthetic depth' using an 11-point numeric and a 5-point verbal
      scale. Bispectral index and spectral entropy were recorded as
      electroencephalogram parameters. The association between the subjective
      assessment and the electroencephalogram parameters was calculated using the
      prediction probability, PK. RESULTS: Association between subjective assessment
      and electroencephalographic parameters showed a tendency to a better prediction
      probability in the experienced group. The difference was significant (P < 0.05)
      for the bispectral index (PK 0.76 +/- 0.01 for experienced and 0.71 +/- 0.01 for
      inexperienced anaesthesiologists). In both groups, a large percentage of the data
      points recorded during surgery showed bispectral index values above the
      recommended value of 60 (13.2% in the experienced and 34.3% in the inexperienced
      group) despite a subjective assessment of 'deep' or 'very deep' anaesthetic
      depth. CONCLUSION: The study demonstrates that the association between
      subjectively assigned values of anaesthetic depth and electroencephalographic
      parameters of anaesthetic depth is better for anaesthesiologists with more
      clinical experience. However, in the 'inexperienced' as well as 'experienced'
      group a high percentage of bispectral index and entropy values above 60 occurred
      despite a subjective assessment of adequate anaesthetic depth. Although there was
      no evidence for explicit memory, this may indicate a risk for memory formation.

PMID- 16438756
TI  - Concordance of antibiotic prophylaxis, direct Gram staining and protected brush
      specimen culture results for postoperative patients with suspected pneumonia.
AB  - BACKGROUND AND OBJECTIVES: Antibiotic therapy alters the diagnostic value of
      protected brush specimens. With protected brush specimens alone, diagnosing
      pneumonia requires 24 or 48 h. Addition of direct Gram staining shortens this
      delay. Antibiotic prophylaxis, recommended after major surgery, may influence the
      contribution of Gram staining to diagnosing postoperative pneumonia. METHODS:
      During a 1-yr period, we retrospectively studied all patients on mechanical
      ventilation suspected of having postoperative pneumonia who had undergone
      fibreoptic bronchoscopy with protected brush specimens. Postoperative pneumonia
      was diagnosed when quantitative protected brush specimens culture results yielded
      103 colony-forming units mL-1. RESULTS: Fifty patients were clinically suspected
      of having postoperative pneumonia after cardiac (n=42), vascular (n=5) or
      thoracic (n=3) surgery. Eleven (22%) samples were obtained during antibiotic
      prophylaxis. Twenty-two (44%) episodes were microbiologically proven. Gram-stain
      sensitivity was 95.5%, with 82.1% specificity, 80.7% positive-predictive value
      and 95.8% negative-predictive value. Concordance between direct Gram-stain
      identified pathogens and Gram stain of cultured pathogens was significantly less
      frequent during antibiotic prophylaxis (63.6%) than afterwards (94.9%) (P<0.05).
      CONCLUSION: Antibiotic prophylaxis diminished the diagnostic value of Gram
      staining of protected brush specimens. When protected brush specimens was
      performed during antibiotic prophylaxis, Gram staining accurately enabled early
      exclusion of postoperative pneumonia because of its excellent negative-predictive
      value. After antibiotic prophylaxis, Gram staining permitted early diagnosis of
      postoperative pneumonia identification of the responsible pathogen.

PMID- 16438757
TI  - Inter-patient variability upon induction with sevoflurane estimated by the time
      to reach predefined end-points of depth of anaesthesia.
AB  - BACKGROUND AND OBJECTIVES: A difficult issue in anaesthesia is its titration for
      an individual patient to avoid over- and underdosage. Common practice is to use
      an initial dose and increase it subsequently if the defined end-point is not
      reached. This assumes that the end-point is reached after a similar interval of
      time in all patients given a similar dose. In order to test this hypothesis we
      measured the time to reach end-points such as loss of consciousness (LOC), a
      bispectral index (BIS) value of 60, the minimal BIS and the minimal mean arterial
      pressure (MAP) values. METHODS: Thirty patients aged 18-60 yr scheduled for
      general surgery were included in this observational study. After preoxygenation,
      induction was performed with 6% inspired concentration of sevoflurane in 6 Lmin-1
      oxygen using the SiBI connector and the tidal volume technique. Remifentanil was
      administered when the BIS value was 60 and tracheal intubation was performed 4
      min later. RESULTS: Time (median, minimum-maximum) to LOC, a BIS value of 60, the
      minimal BIS and MAP values were, respectively, 75 (45-135), 120 (75-270), 300
      (120-720) and 450 (120-1200) seconds. The time to the minimal BIS value was
      significantly (P < 0.05) shorter than the time to reach the minimal MAP value.
      CONCLUSIONS: These results demonstrate large inter-patient variability for the
      time necessary to reach defined end-points of depth of anaesthesia when a similar
      dose of anaesthetic is given. Measuring the time to reach a predefined BIS value
      would allow application of nociceptive stimuli only at adequate levels of
      hypnosis and would facilitate titration.

PMID- 16438758
TI  - The effects of sufentanil or morphine added to hyperbaric bupivacaine in spinal
      anaesthesia for caesarean section.
AB  - BACKGROUND AND OBJECTIVE: The quality of spinal anaesthesia, often used for
      Caesarean section, can be improved by adding an opioid to the local anaesthetic.
      This study compared the quality of anaesthesia, postoperative analgesia, and
      adverse effects on mother and neonate when either sufentanil 5 microg or morphine
      0.2 mg was added to intrathecal hyperbaric bupivacaine for Caesarean section.
      METHODS: This prospective, randomized and double-blind study encompassed 54
      females undergoing Caesarean section. Spinal anaesthesia was obtained with 2 mL
      of 0.5% bupivacaine supplemented with either 0.2 mg morphine or 5 microg
      sufentanil. Characteristics of spinal block, intraoperative analgesia, maternal
      and neonatal side-effects and the time to first request for analgesics were
      assessed. RESULTS: There were no differences in the onset time of sensory block,
      time to sensory block to T10, time to highest sensory block, highest sensory
      block level, time to regression of sensory block to T10 level and time to
      resolution of motor blockade. Perioperative haemodynamic parameters, neonatal
      Apgar scores, neurological and adaptive capacity scores, umbilical blood gas
      values, sedation scores, nausea-vomiting and pruritus incidences were similar in
      both groups. The time to the first request for an analgesic was significantly
      longer (19.5 +/- 4.7 h vs. 6.3 +/- 5.2 h) in patients given morphine (P < 0.05).
      CONCLUSIONS: The addition of 5 microg sufentanil or 0.2 mg morphine to hyperbaric
      bupivacaine for Caesarean section both provided safe and effective anaesthesia.
      Morphine increased the duration of postoperative analgesia compared with
      sufentanil without increasing maternal or neonatal side-effects.

PMID- 16438759
TI  - Effect of topical tranexamic acid in open heart surgery.
AB  - BACKGROUND AND OBJECTIVE: Cardiopulmonary bypass is known to induce postoperative
      coagulopathy including fibrinolysis. We have evaluated the effect of the topical
      use of tranexamic acid in the pericardial cavity on postoperative bleeding
      following open heart surgery. METHODS: One hundred patients, scheduled for
      elective open heart surgery, were included in this double-blind, prospective,
      randomized, controlled study. They were allocated to a treatment group (Group I),
      or placebo group (Group II). Patients with coagulopathies, renal failure, re-do
      surgery, or recent anti-platelet treatment were excluded. In Group I, tranexamic
      acid (2 g in 100 mL of saline solution) was poured into the pericardial cavity
      before sternal closure. Placebo patients received 100 mL of saline. Postoperative
      blood loss, need for transfusion of blood products and the rate of re-sternotomy
      for bleeding were documented. RESULTS: During the first postoperative 24 h,
      cumulative blood loss was significantly higher in Group II compared to Group I
      (1208 +/- 121 mL vs. 733 +/- 93 mL, respectively) (P < 0.001). More blood
      transfusions were administered to Group II patients (4.54 +/- 1.4 units) as
      compared to Group I patients (2.64 +/- 1.5 units) (P < 0.01). CONCLUSION: Topical
      application of tranexamic acid in patients undergoing primary open heart surgery
      led to a significant reduction of both postoperative mediastinal bleeding, and
      rate of re-exploration for haemostasis.

PMID- 16438760
TI  - Axillary and tympanic membrane temperature measurements are unreliable early
      after cardiopulmonary bypass.
AB  - BACKGROUND AND OBJECTIVE: Inaccurate measurements of body temperature following
      cardiopulmonary bypass may be associated with serious complications. The purpose
      of this study was to determine whether axillary and tympanic temperature
      measurements correlate with the urinary bladder temperature in the early
      postcardiac surgery period. METHODS: Forty-nine adult patients who underwent
      cardiac surgery under cardiopulmonary bypass at our institution were
      prospectively studied. Urinary bladder, right axillary, right tympanic and left
      tympanic temperature measurements were simultaneously recorded at 0, 6, 12 and 18
      h following cardiopulmonary bypass. Patients had one to four sets of recordings
      and a total of 629 temperature measurements were recorded. The mean difference
      (bias) between the bladder and each of the other methods and limits of agreement
      were calculated using Bland and Altman method. RESULTS: The mean core body
      temperature recorded from the bladder on admission to the intensive care unit was
      36.4 degrees C. After 6, 12 and 18 h the mean core body temperature was 37.4
      degrees C (range: 35.2-39.0), 37.5 degrees C and 37.45 degrees C, respectively.
      The mean differences (bias) between the bladder temperature and the other three
      methods were: left tympanic, 0.65 degrees C (95% CI: -0.24 to 1.58); right
      tympanic, 0.57 degrees C (95% CI: -0.48 to 1.63) and right axillary, 0.55 degrees
      C (95% CI: -0.27 to 1.36). CONCLUSIONS: The axilla and tympanic membrane are
      unreliable sites for core body temperature measurement early after
      cardiopulmonary bypass in adult patients and clinical decisions should be based
      on more reliable methods.

PMID- 16438761
TI  - Current practice in regional anaesthesia in Germany.
AB  - BACKGROUND AND OBJECTIVE: Several new techniques and agents (e.g. ropivacaine)
      have been introduced in regional anaesthesia to improve patients outcome and
      safety. The beneficial effects on patient outcome are clear with these
      techniques, however, no information is available about their pattern and
      frequency of use in clinical practice. This study presents data concerning the
      current practice of regional anaesthesia in Germany. METHODS: A questionnaire was
      sent to every German anaesthesia department (n = 1381). Questions focused on the
      frequency and range of regional anaesthetic procedures employed, with attention
      also to the organizational structural of the individual institution. RESULTS: Six
      hundred and sixty-seven questionnaires were returned anonymously, representing a
      return rate of 48.3%. In hospitals with less than 200 beds, the number of
      regional anaesthetics was markedly higher compared to large hospitals with more
      than 400 beds. In contrast, small hospitals tended to provide only basic
      techniques of regional anaesthesia, whereas larger hospitals implemented more
      advanced techniques. Bupivacaine remains the most commonly used long-lasting
      local anaesthetic. Staff structure was also different in small departments -
      patient care was performed by board certified anaesthesiologists while residents
      were responsible for the patients in larger departments. CONCLUSIONS: In small
      hospitals a majority of board certified anaesthesiologists rely on basic regional
      anaesthesia techniques. In large departments some consultants provide the entire
      spectrum of regional anaesthesia, with the majority of cases transferred to the
      residents responsibility. These results indicate the strong need to improve
      residency programs with regard to regional anaesthesia.

PMID- 16438762
TI  - Esomeprazole for the prevention of postoperative nausea and vomiting. A
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Postoperative nausea and vomiting still represents a major problem
      after surgery. Although risk factors for postoperative nausea and vomiting and
      procedures to reduce postoperative nausea and vomiting have been described, the
      incidence of postoperative nausea and vomiting remains high. The aim of the
      present study was to investigate the potential role of the proton pump inhibitor
      esomeprazole to reduce postoperative nausea and vomiting after elective surgery.
      METHODS: In a randomized, double-blind trial, ASA I-III patients at high risk for
      postoperative nausea and vomiting received esomeprazole tablets 3 x 40 mg or
      matching placebo the evening before surgery, 2 h preoperatively and 24 h
      postoperatively. Total intravenous anaesthesia with propofol and remifentanil
      without nitrous oxide (FiO2 0.5) was used. Patients were interviewed using a
      standardized postoperative nausea and vomiting questionnaire at discharge from
      the post-anaesthesia care unit, 6 h and 24 h later. The severity of nausea was
      estimated on a 0-100 point numerical scale (0 = no nausea, 100 = maximum nausea).
      RESULTS: The incidence of vomiting was similar in the esomeprazole (n = 45) and
      the placebo (n = 48) groups (64.4% vs. 60.5%, P > 0.05). The average nausea score
      was 17.8 with esomeprazole and was 18.7 with placebo (P > 0.05). Only 24.7% of
      all patients (esomeprazole 24.4%, placebo 25.0%) did not experience any nausea or
      vomiting. CONCLUSION: There is no evidence that prophylactic esomeprazole reduces
      the incidence of postoperative nausea and vomiting or the degree of postoperative
      nausea.

PMID- 16438763
TI  - A randomized, prospective double-blind comparison of the efficacy of generic
      propofol (sulphite additive) with diprivan.
AB  - BACKGROUND AND OBJECTIVE: We compared the dose requirement and side effect
      profile of total intravenous anaesthesia using Diprivan to generic propofol at a
      specific anaesthetic target level utilizing the bispectral index monitor to
      determine efficacy differences between the two products. METHODS: Sixty women
      undergoing abdominal hysterectomy were induced with propofol 2 mg kg-1 and
      maintained with infusion (20-200 microg kg-1 min-1) adjusted to maintain a
      bispectral index of 50-65. Plasma propofol concentration was measured at 1 and 2
      h post induction in 25 patients. RESULTS: Mean (SD) drug doses adjusted for
      weight and time were similar in the Diprivan and generic propofol groups: 90 (30)
      microg kg-1 min-1 vs. 90 (20) microg kg-1 min-1 respectively. Mean (SD) plasma
      propofol levels at 1 and 2 h were also similar (3.0 (1.0) microg mL-1 vs. 3.6
      (1.4) microg mL-1, P = 0.2 and 3.0 (1.9) microg mL-1 vs. 3.4 (1.6) microg mL-1, P
      = 0.58). CONCLUSIONS: Diprivan and generic propofol have similar efficacy at a
      specified, bispectral index-defined, depth of anaesthesia.

PMID- 16438764
TI  - Effects of intra-aortic balloon counterpulsation on parameters of tissue
      oxygenation.
AB  - BACKGROUND AND OBJECTIVE: To investigate the effects of intra-aortic balloon pump
      therapy on parameters of global and regional oxygenation in patients undergoing
      cardiac surgery. METHODS: As part of a large surveillance study in cardiac
      surgery patients (n=266) we retrospectively analyzed the course of 28 patients
      requiring intra-aortic balloon pump therapy. Patients were grouped according to
      the time point of pump insertion (during weaning from cardiopulmonary bypass:
      group early intra-aortic balloon pumping (n=17); after admission to the intensive
      care unit: group late intra-aortic balloon pumping (n=9). Haemodynamic and
      tonometric variables, arterial lactate, and use of catecholamines were measured
      hourly. MEASUREMENTS AND RESULTS: Cardiac index increased in both groups after
      intra-aortic balloon pump insertion (2.2+/-0.5 baseline; 3.4+/-0.8 L min-1 m-2 4
      h later (group early intra-aortic balloon pumping); 2.8+/-0.5 baseline, 3.6+/-L
      min-1 m-2 4 h later (group later intra-aortic balloon pumping), each P<0.05),
      there were no differences between groups. Arterial lactate values increased in
      group later intra-aortic balloon pumping after pump insertion to a maximum 2 h
      later (8.4+/-6.1 mmol L-1 baseline; 12.7+/-7.4 mmol L-1, P<0.05), and decreased
      continuously afterwards. The difference of arterial and gastric CO2 showed a
      sharp decrease after pump insertion in group later intra-aortic balloon pumping
      (26.4+/-9.8 baseline; 7.0+/-11.1 mmHg, P<0.05). There were no differences between
      groups. Epinephrine doses were higher in group later intra-aortic balloon pumping
      (P<0.05). CONCLUSIONS: Intra-aortic balloon pump therapy improved global and
      regional splanchnic oxygenation in cardiac surgery patients with low-cardiac
      output syndrome. Gastro-intestinal tonometry could provide additional information
      concerning tissue oxygenation. Patients with later intra-aortic balloon pump
      insertion needed more catecholamine therapy to achieve similar haemodynamic
      values.

PMID- 16438765
TI  - Instantaneous diastolic pressure-flow relationship in arterial coronary bypass
      grafts.
AB  - OBJECTIVE: The objective of this study was to describe the diastolic pressure
      flow relationship and to assess critical occlusion pressure in arterial coronary
      bypass grafts in human beings. METHODS AND RESULTS: Fifteen patients were studied
      following elective surgical coronary artery bypass grafting. Flow in the left
      internal mammary artery bypass to the left anterior descending artery was
      measured and simultaneously, aortic pressure, coronary sinus pressure and left
      ventricular end-diastolic pressure were recorded. The zero-flow pressure
      intercept as a measure of critical occlusion pressure was extrapolated from the
      linear regression analysis of the instantaneous diastolic pressure-flow
      relationship. Mean diastolic flow was 46 +/- 17 mL min(-1), mean diastolic aortic
      pressure was 60.5 +/- 10.0 mmHg. Diastolic blood flow was linearly related to the
      respective aortic pressure in all patients (R-values 0.7-0.99). The regression
      lines had a mean slope of 2.1 +/- 1.2 mL min(-1) mmHg(-1). Mean critical
      occlusion pressure was 32.3 +/- 9.9 mmHg and exceeded mean coronary sinus
      pressure and mean left ventricular end-diastolic pressure by factors of 3.1 and
      2.6, respectively. CONCLUSIONS: Our data demonstrate the presence of a vascular
      waterfall phenomenon in the coronary circulation after internal mammary artery
      bypass grafting. Critical occlusion pressure in arterial grafts considerably
      exceeds coronary sinus pressure as well as left ventricular end-diastolic
      pressure and should thus be used as the effective downstream pressure when
      calculating coronary perfusion pressure. Our data further suggest that the slope
      of diastolic pressure-flow relationships provides a more rational approach to
      assess regional coronary vascular resistance than conventional calculations of
      coronary vascular resistance.

PMID- 16438766
TI  - Teaching basic life support to nurses.
AB  - BACKGROUND AND OBJECTIVE: Every member of healthcare personnel should be able to
      perform basic life support including defibrillation (CPR-D). The biggest cost of
      implementation is training and these costs need to be reduced. The purpose of
      this randomized study was to evaluate the applicability of distance learning as a
      method to teach CPR-D. METHODS: Nurses (n = 56) working in a geriatric hospital
      were randomized into three groups. The first group was given the Internet-based
      CPR-D course and the second was given a traditional, small-group CPR-D course. A
      third group without specific training in CPR-D served as a control group. An
      objective structured clinical examination (OSCE) was performed 2 weeks after the
      courses with a manikin patient having a cardiac arrest. RESULTS: The median score
      of all participants was 31/49 (range 21-38). The reliability of the checklist was
      adequate (Cronbach alpha 0.77). Nurses receiving traditional CPR-D performed
      better than those receiving the Internet-based course (median score 34 vs. 28, P
      < 0.05) and the control group (median score 34 vs. 26, P < 0.0001). Nurses
      receiving Internet-based course performed similarly as the control group (median
      score 28 vs. 26, ns). CONCLUSIONS: Distance learning cannot substitute for
      traditional small-group learning.

PMID- 16438767
TI  - Fluid preload before spinal anaesthesia in Caesarean section: the effect on
      neonatal acid-base status.
AB  - BACKGROUND AND OBJECTIVE: We evaluated the effect of two different preload
      solutions: (i) Ringer's lactate (compound sodium lactate intravenous infusion BP)
      and (ii) 0.9% sodium chloride solution on the neonatal acid-base status of the
      newborn infants. The two standard regimens were compared to detect a possible
      difference. METHODS: A 2 L crystalloid fluid bolus was administered immediately
      before spinal anaesthesia for elective Caesarean section in two groups of 20
      healthy parturients, while rigorously maintaining maternal normotension. RESULTS:
      No significant differences in the Apgar scores at 1 and 5 min, or infant well
      being were demonstrated in either of the two groups. The data show that umbilical
      artery PCO2 is lower in the Ringer's lactate group and that pH is insignificantly
      higher by 0.03. CONCLUSIONS: The choice of Ringer's lactate or saline for fluid
      preload does not have any effect on neonatal well-being.

PMID- 16438768
TI  - Monitoring sedation in critically ill patients: bispectral index, Ramsay and
      observer scales.
AB  - BACKGROUND AND OBJECTIVE: Sedation is commonly required by critically ill
      patients and inadequate sedation may be hazardous. Traditionally, subjective
      scales have been used for monitoring sedation. Bispectral index has been
      proposed, although its utility in the intensive care unit is debated. Our aim was
      to evaluate the depth of sedation in intubated surgical critically ill patients
      by means of two sedation scales (Ramsay and Observer's Assessment of Alertness
      and Sedation) and bispectral index. METHODS: Sedation was assessed prospectively
      in 50 postoperative intubated patients requiring at least 24 h of sedation (35
      propofol, 15 midazolam/fentanyl), every 8 h for a 24 -h period. The bispectral
      index value recorded was the mean value obtained during a 10-min observation
      period, whenever the quality signal index was above 75% and the electromyographic
      signal was below 25%. RESULTS: Most of the patients (78%) were oversedated
      (bispectral index < 60). The three sedation scores (global data) correlated
      significantly (P < 0.001). This correlation was lost in the midazolam group in
      which the patients were also significantly more sedated than the propofol group
      (P = 0.001). The correlation between the bispectral index and the scales in the
      midazolam group reappeared when the measurements with a Ramsay = 6 or an
      Observer's Assessment of Alertness and Sedation = 1 were excluded. CONCLUSIONS:
      Sedation should be monitored routinely in intensive care units. The Ramsay and
      the Observer's Assessment of Alertness and Sedation scales showed equal efficacy.
      Bispectral index might prove useful for discriminating between deeper levels of
      sedation.

PMID- 16438769
TI  - A comparison of infero-nasal and infero-temporal sub-Tenon's block.
AB  - BACKGROUND AND OBJECTIVE: Sub-Tenon's block is usually delivered by the infero
      nasal (IN) approach, but occasionally this may not be possible. The infero
      temporal (IT) approach has been described, but data is not available on its
      efficacy. METHODS: One hundred patients undergoing cataract extraction were
      randomized to receive an IN or IT sub-Tenon's injection of lidocaine 2% with
      hyaluronidase 15 IU mL-1. Akinesia was assessed using the Brahma scale at 0, 2,
      4, 6 and 8 min. Injection, intraoperative and postoperative pain scores (verbal
      analogue score, 0-10) were noted, along with the incidence of sub-conjunctival
      haemorrhage and chemosis. RESULTS: There were no differences in patient
      characteristics data, or mean volume of administered local anaesthetic solution
      (3.3 (SD = 0.4) mL). There were no significant differences between groups in
      terms of onset of akinesia. Mean akinesia scores at 2, 4, 6 and 8 min were 2.7,
      1.1, 0.4 and 0.2 for Group IN, compared to 2.2, 0.9, 0.8 and 0.3 for Group IT.
      Chemosis occurred in 14 patients in Group IN, compared to 22 in Group IT (P =
      0.21).A sub-conjunctival haemorrhage was noted in 14 patients in Group IN and 19
      patients in Group IT (P = 0.52). No patients required supplementary injections.
      Mean pain scores for the injection, intraoperatively and postoperatively were
      0.9, 0 and 0 for Group IN, compared to 1.1, 0 and 0 for group IT. The surgeons
      scored all the blocks as 'good' except for one patient in each group.
      CONCLUSIONS: The IT approach provides an equally rapid onset of block, without a
      significant increase in complications.

PMID- 16438770
TI  - Propofol inhibits potassium chloride induced contractions of isolated human
      umbilical vessels.
AB  - BACKGROUND AND OBJECTIVE: We have evaluated the effects of propofol and its
      relationship with K+ channels on human isolated umbilical vessels. METHODS:
      Umbilical vessel rings were suspended in isolated organ baths containing Krebs
      Ringer solution. In the first series of experiments the effect of propofol (10(
      9)-10(-4) M) was examined in a concentration-dependent manner on umbilical
      vessels precontracted with KCl (60 mmol). In the second series, these effects
      were studied in the presence of tetraethylammonium. RESULTS: A mild contraction
      was produced by low dose propofol in both precontracted umbilical artery and
      umbilical vein segments. 10(-4) M propofol caused significant relaxation in both
      umbilical artery and umbilical vein. The relaxation response was significantly
      reduced by the addition of 10(-1) M tetraethylammonium. CONCLUSION: These results
      suggested that the responses of propofol on KCl-induced contractions of both
      umbilical artery and vein were dose dependent, and this effect involved Ca2+
      activated K+ channels.

PMID- 16438771
TI  - Telemedicine for acute burn treatment: the time has come.
AB  - This brief paper sets out the arguments for the routine use of telemedicine in
      the evaluation of burns. Two cases are reported from the author's practice that
      show the need for it.

PMID- 16438772
TI  - Telemedicine systems and telecommunications.
AB  - Successful telemedicine requires appropriate equipment and some kind of
      telecommunications medium. However, successful telemedicine requires more than
      just technology. The three essential components are the personnel, the technology
      and a liberal measure of perseverance. Before the technology can be selected, it
      is necessary to consider the nature of the information to be transmitted between
      the sites and the time frame over which it must be sent to achieve the desired
      clinical goals, because this will determine the choice of equipment and the
      telecommunications network. Factors to be considered include the types of
      information to be transmitted, the quantity of information to be transferred, and
      security and privacy (e.g. in Europe and the USA there has been recent
      legislation about data security). The choice of transmission method for any
      telemedicine application is, in practice, a compromise between what one would
      like and what one can afford. In practice, various trade-offs have to be made,
      which include cost, availability of the service (i.e. the coverage), bandwidth,
      reliability and quality of service. Equipment and the telecommunications medium
      are a necessary, but not sufficient, pre-requisite for a successful telemedicine
      programme. The right people are also required and they must be properly trained.

PMID- 16438773
TI  - Telemedicine for delivery of health care in Parkinson's disease.
AB  - We have used telemedicine at the Seattle Veterans Administration Medical Center
      to deliver follow-up care to patients with Parkinson's disease (PD). Patients
      were located at eight facilities which were 67-2400 km from the medical centre.
      Each facility had videoconferencing equipment (connected by Internet Protocol at
      384 kbit/s), and computer terminals that could access the patient's electronic
      medical record. Over a three-year period, we used telemedicine for 100 follow-up
      visits on 34 PD patients. Visits lasted 30-60 min. Patients and providers were
      satisfied with the use of the technology. Savings amounted to approximately 1500
      attendant travel hours, 100,000 travel kilometres, and US 37,000 dollars in
      travel and lodging costs. For the first 82 telemedicine visits, the video quality
      was inadequate for scoring all components of the motor Unified Parkinson Disease
      Rating Scale (UPDRS). For the last 18 visits, a different videoconferencing unit
      produced better video quality, which was satisfactory for motor UPDRS
      measurements, except for components that required physical contact with the
      patient (rigidity and retropulsion testing). Our experience shows that
      telemedicine can be used effectively for follow-up visits with selected PD
      patients who are unable to travel.

PMID- 16438774
TI  - Remote ophthalmology services: cost comparison of telemedicine and alternative
      service delivery options.
AB  - We calculated the cost of an established tele-ophthalmology service, from a
      health-provider's perspective, and compared this with the cost of three other
      existing eye-care service delivery options. During a 12-month study period, 118
      persons took part in the tele-ophthalmology consultations between a rural clinic
      located approximately 900 km from the Lions Eye Institute in Perth. The variable
      costs of tele-ophthalmology were 166.89 dollars(Australian dollars) per patient,
      and the alternatives cost 445.96 dollars, 271.48 dollars and 665.44 dollars per
      patient. Tele-ophthalmology incurred a set-up cost of 13,340 dollars. The
      threshold at which tele-ophthalmology became cheaper than any of the alternative
      options occurred at a workload of 128 patients. Tele-ophthalmology offers a
      viable alternative to conventional eye-care service in rural and remote areas.

PMID- 16438775
TI  - Use of 3G mobile phone links for teleconsultation between a moving ambulance and
      a hospital base station.
AB  - We developed a mobile teleconsultation system based on third-generation mobile
      phone links. The system comprised a laptop computer and a digital camcorder. It
      was installed inside an ambulance to allow video-conferencing between the moving
      vehicle and a doctor at a base station. In addition to video and voice, high
      quality still images could also be transmitted. A series of 17 trial runs with
      real ambulance patients was conducted in the city of Athens. In general, the
      videoconferencing sessions produced relatively clear video. The bandwidth was
      high enough for a satisfactory video of 10-15 frames/s. During a total testing
      period of 23 h and in an area of about 180 km2, there were nine instances of
      signal loss, amounting to a total of 17 min. The general opinion formed by the
      doctors was that the system produced good results. All initial diagnoses made
      using the system agreed with the final diagnoses of the patients. The study
      showed that the mobile system could reduce the time before an ambulance patient
      is seen by a doctor.

PMID- 16438776
TI  - Organizational centralization in radiology.
AB  - Traditionally, hospitals have a radiology department, where images are taken and
      interpretation occurs. Teleradiology makes it possible to capture images in one
      location and transmit them elsewhere for interpretation. Organizational
      centralization of radiology interpretations is therefore of interest. Empirical
      data have been collected in qualitative interviews of 26 resource persons with
      substantial experience with picture archiving and communication systems and
      teleradiology, from 12 departments of radiology in Norway. The response rate was
      90%. A total of 21 theoretically possible types of centralization of image
      interpretation were identified, representing combinations of three categories of
      geographical centralization, and seven categories of centralization according to
      function. Various advantages and disadvantages of centralization were identified.
      Organizational changes may be decisive for the future of teleradiology, but it
      may be wise to plan for change in small steps, since we know little about how
      broad future organizational changes based on teleradiology will be, or what will
      decide how far particular organizations will go.

PMID- 16438777
TI  - Email teleconsultations: well formulated clinical referrals reduce the need for
      clinic consultation.
AB  - We examined how well primary-care physicians formulated their clinical referrals
      when asking for help with patient-related clinical problems using an email-based
      teleconsultation service. Over 100 family physicians made use of the service. The
      specialists were medical school faculty members. The service was initiated in May
      1996 with 19 specialists and expanded to 34 specialties over the next five years.
      A total of 1618 patient-related clinical questions were analysed, the outcome for
      the analysis being whether specialists recommended a clinic consultation.
      Specialists recommended a clinic consultation in response to 10% of their
      clinical questions about patients. There was a strong association between how
      family physicians formulated their clinical questions and whether the specialist
      recommended a clinic consultation. When the family physicians specified a
      clinical task (P < 0.001), intervention (P = 0.004) and outcome (P < 0.001) in
      their questions, specialists were less likely to recommend a clinic consultation.
      This influence was independent of the amount of clinical information included
      with the question (P > 0.05). About 5% of the questions that included all three
      question components resulted in the recommendation for a clinic consultation,
      compared with nearly 30% of the questions containing none of these components.
      How family physicians formulate their clinical questions influences whether
      specialists request a clinic consultation.

PMID- 16438778
TI  - Effect of telemedicine on patients' diagnosis and treatment.
AB  - We conducted a post-consultation survey during 1998-2002 (n = 412 consultations)
      in the Rural Hospital Telehealth Project run by the University of Arkansas for
      Medical Sciences. Changes in the patient's diagnosis and treatment plan as a
      result of the telemedicine session were assessed. There were 47 consultants, who
      conducted 2-82 consultations each. The teleconsultants established a diagnosis in
      74 consultations. This was 26% of the 286 respondents. Of the 63 respondents for
      cases where there was a prior diagnosis and a change was applicable, 17
      consultants (27%) reported that there was a change in the patient's diagnosis.
      The consultants established a patient treatment plan in 139 consultations. This
      was 52% of the 268 respondents. Of the 123 respondents for cases where there was
      a prior treatment plan and a change was applicable, 82 (67%) consultants reported
      a change in the treatment plan. The changes in diagnosis and management imply
      benefits for the rural population in Arkansas as a result of the use of
      telemedicine.

PMID- 16438779
TI  - Remote support for emergency medicine using a remote-control laser pointer.
AB  - We have developed a laser pointing system, the GestureLaser, which allows a
      remote operator to control a videocamera and a laser beam via a networked
      personal computer. The laser spot can be moved by the mouse cursor controlled by
      the remote instructor. The system was tested by giving remote instruction in
      thoracentesis to inexperienced operators using a training mannekin. Seven medical
      students received instructions using the laser pointer and another seven received
      instruction without the laser pointer. All operators completed the task
      correctly. The laser pointer group correctly identified the centesis space and
      performed the task on the first trial. When the laser pointer was not used, four
      operators (57%) made a mistake in selecting the centesis space at the first
      trial. The mean times for both stage 1--verbal versus GestureLaser 59 s (SD 13)
      versus 44 s (SD 5), p = 0.015 - and stage 2--verbal versus GestureLaser 98 s (SD
      20) versus 64 s (SD 7), P = 0.002 - were significantly shorter when the
      GestureLaser was used. The study shows that the laser pointing system can be used
      to remotely instruct a novice operator in performing thoracentesis. It could
      improve collaboration between geographically separated sites.

PMID- 16438780
TI  - Expanding the theoretical foundations of telemedicine.

PMID- 16438781
TI  - A mini-questionnaire to assess the acceptability of an environmental,
      unobtrusive, patient-monitoring device.

PMID- 16438782
TI  - Does restructuring hospitals result in greater efficiency?--An empirical test
      using diachronic data.
AB  - Hospitals are being restructured more frequently. Increased cost efficiency is
      the usual justification given for such changes. All 20 major teaching hospitals
      in Australia's two most populous states were investigated by classifying each
      over a 5-6 year period in terms of their cost efficiency (average cost per case
      weighted by Australian diagnosis-related group [AN-DRG] data and adjusted for
      inflation) and structure, categorized as traditional-professional (TP), clinical
      divisional (CD), or clinical-institute (CI). In all, 12 hospitals changed
      structure during the study period. There was slight evidence that CD structures
      were more efficient than TP structures but this was not supported by other
      evidence. There were no significant differences in efficiency in the first or
      second years following changes from either TP to CD or TP to CI structures. All
      four hospitals changing from CD to CI structure became significantly less
      efficient. This may be due to frequency rather than type of change as they were
      the only hospitals that implemented two structural changes. Hospitals that
      changed or did not change structure were similar in efficiency at the beginning
      and at the end of the study period, in overall efficiency during the period, and
      in trends toward efficiency over time. The findings challenge those who advocate
      restructuring hospitals on the grounds of improving cost efficiency.

PMID- 16438783
TI  - Hospital admissions: who is admitted through the emergency department?
AB  - This study examines the co-variates that separate patients who presented an
      emergent condition without a physician referral and were admitted through the
      hospital emergency department (ED) from their counterparts who were referred by a
      physician for the treatment of an elective or urgent condition and were admitted
      through the admissions department. The analysis was based on 295,945 inpatient
      admissions in 1999 to short-term acute-care hospitals in Oklahoma. Employing
      hospital admission as the unit of analysis, logistic regression was used to
      examine the differential likelihood of admission without a physician referral and
      through the ED of the uninsured, Medicare beneficiaries, Medicaid recipients,
      African Americans and Native Americans. The results of the logistic regression
      analysis indicated that Medicaid recipients and the uninsured were more likely
      than their commercially-insured counterparts to be admitted, without a physician
      referral, to an acute-care hospital in Oklahoma following an evaluation in the
      ED. The findings also suggest that African Americans and, to a lesser extent,
      Native Americans were more likely than their white counterparts to be admitted
      through the ED without benefit of a physician referral.

PMID- 16438784
TI  - User charges in public health facilities in Tanzania: effect on revenues, quality
      of services and people's health-seeking behaviour for malaria illnesses in
      Korogwe district.
AB  - User charges in public health facilities are aimed at improving efficiency and
      quality of health services. In Africa, evidence about their effect on patient
      attendance and community health-seeking behaviour are mixed. This paper reports a
      study of the effect of user charges on revenue collection, quality of services
      and people's health-seeking behaviour in relation to malaria in Korogwe district,
      Tanzania. Data were collected through focus-group discussions with community
      members, interviewing community leaders and health workers, field observations
      and review of patient registers. Generally, there was no distinct difference in
      the trends of patient attendances before and after user fee introduction. Public
      awareness about cost-sharing policy was high, but had low appreciation in the
      administration of exemptions and waivers. Shortage of drugs, laboratory
      facilities, and inhospitality of nurses lowered their confidence in the user-fee
      system. Autonomy to collect and prioritize expenditure of user-fee revenue at the
      health-facility level was appreciated by community leaders and health workers
      who, however, had reservations with funds being held at the district level and
      delays by the DMO's office in approving budgets submitted in request for
      expenditure of such revenues. Thus, despite the potential of user charges for
      revenue mobilization, problems with their administration lowers public confidence
      in the user-fee system improving quality and accessibility of services to the
      poor.

PMID- 16438785
TI  - Influenza outbreaks and hospital bed occupancy in Rome (Italy): current
      management does not accommodate for seasonal variations in demand.
AB  - OBJECTIVE: Our goal was to assess how different hospital wards react to influenza
      epidemics, and whether related specialties cooperate in coping with winter bed
      crises. STUDY DESIGN: The Lazio Hospital Information System (HIS) dataset from
      July 1998 to June 2001 was used for the study. The HIS collects data on all
      hospital discharges. We considered diagnosis-related groups (DRG) as the reason
      for hospital stay and used DRG to classify admissions as influenza related or
      influenza unrelated. Time series analysis of daily bed occupancy in different
      specialty areas by influenza-related and influenza-unrelated cases was performed.
      Generalized additive models (GAMs) were used to take the effect of short-term and
      seasonal bed occupancy into account on influenza-related occupancy. RESULTS:
      Influenza-related bed occupancy ranges from 770 patients/day during the influenza
      season to 525 patients/day during the rest of the year. Daily occupancy by
      influenza-related cases represents 2.8% of total hospital occupancy and 7% of
      general medicine occupancy during the influenza season. When comparing the
      influenza season with the rest of the year, general medicine occupancy by
      influenza-related cases increases by 51% versus the 25-32% increase in other
      specialty wards. Little change in daily occupancy by influenza-unrelated cases
      was observed in all specialties when comparing the influenza season with the rest
      of the year. CONCLUSIONS: Hospital specialty wards react poorly and single
      handedly to a minor and predictable burden. Any winter bed crisis in the Lazio
      region is probably the result of defective management of available beds more than
      excess in demand.

PMID- 16438786
TI  - Organizational strategies to tackle health-care disparities in the USA.
AB  - US health policy is beginning to address health-care disparities, mainly in terms
      of racial/ethnic groups and access to care for vulnerable groups. Though not
      widespread, policies are engaging a wide range of organizations, including
      federal, state and local government, insurers, providers and philanthropic
      foundations. It initially seems strange that US health-care organizations (HCOs)
      are seeking to tackle disparities, as the system itself generates huge
      disparities. This article reviews the reasons underlying growing interest in
      disparities in the USA, examines the barriers and opportunities facing such
      initiatives and considers their likely impact. Demographic changes, efforts to
      widen access to care and to remedy health-care discrimination are the primary
      factors in driving these initiatives. HCOs (and others) are faced with
      implementation barriers including structural impediments of the health-care
      system, the limited extent to which the issue has permeated within HCOs, and data
      collection. Opportunities for progress can be garnered from the mounting evidence
      base, the various programmes being implemented, and emerging links with quality
      improvement initiatives. The USA is faced with ongoing efforts to keep the issue
      on the (policy and managerial) agenda, to integrate strategies into
      organizational systems and processes, and to monitor the effects of such
      strategies.

PMID- 16438787
TI  - Comparing hospital staff and patient perceptions of customer service: a pilot
      study utilizing survey and focus group data.
AB  - The measurement of patient satisfaction is crucial to enhancing customer service
      and competitive advantage in the health-care industry. While there are numerous
      approaches to such measurement, this paper provides a case study which compares
      and contrasts patient and staff perceptions of customer service using both survey
      and focus group data. Results indicate that there is a high degree of correlation
      between staff and patient perceptions of customer service based on both survey
      and focus group data. However, the staff and patient subgroups also provided
      complementary information regarding patient perceptions of their service
      experience. Staff members tended to have more negative perceptions of service
      attributes than did the patients themselves. The focus group results provide
      complementary information to survey results in terms of greater detail and more
      managerially relevant information. While these results are derived from a pilot
      study, they suggest that diversification of data sources beyond patient surveys
      may enhance the utility of customer service information. If further research can
      affirm these findings, they create exciting possibilities for gathering valid,
      reliable and cost-effective customer service information.

PMID- 16438788
TI  - Enantiomer separation of a novel aminothiazolecarboxamide fungicide using
      polysaccharide-derived chiral stationary phases.
AB  - The direct enantioseparation of a novel aminothiazolecarboxamide fungicide,
      ethaboxam, on polysaccharide-derived chiral stationary phases (CSPs) is
      described. Good resolution is achieved with several polysaccharide-derived CSPs.
      Chiralcel OD (OD-H) and Chiralpak AS are excellent for direct enantiomer
      separation of ethaboxam. The elution behavior and the effects of eluent
      composition on the resolution of ethaboxam are also investigated. Furthermore,
      the mechanism for chiral recognition using molecular mechanics is discussed.

PMID- 16438789
TI  - Improvement of the chromatographic separation of several 1,4-dihydropyridines
      calcium channel antagonist drugs by experimental design.
AB  - A high-performance liquid chromatographic method with diode array detection has
      been developed and optimized for the separation of five calcium channel blockers
      belonging to the 1,4-dihydropyridine subgroup (nifedipine and related drugs). The
      possibility of the simultaneous drug analysis allows a decrease of time during
      the assay as well as a saving of reagents and solvents. In this work, the effect
      of four experimental parameters (organic modifier percentage, pH value,
      concentration of the buffer in the mobile phase, and column temperature) on the
      chromatographic resolution are investigated by experimental design in order to
      optimize the chromatographic separation of five 1,4-dihydropyridines (amlodipine,
      nitrendipine, felodipine, lacidipine, and lercanidipine). Fractional factorial
      design, central composite design, and finally the Multisimplex program are used
      to establish the optimal conditions in terms of resolution and minimum analysis
      time. Optimal separation of the five compounds under study is achieved in less
      than 12 min using a Sulpecosil LC-ABZ+Plus C18 column, a composition of mobile
      phase of acetonitrile-10mM acetic acid acetate buffer pH 5 (72:28, v/v) at a flow
      rate of 1 mL/min, a column temperature of 30 degrees C +/- 0.1 degrees C, and a
      detection wavelength of 238 nm.

PMID- 16438791
TI  - HPLC separations with micro-bore columns using high-temperature water and flame
      ionization detection.
AB  - Previous work demonstrates that a flame ionization detector (FID) may be used as
      a detector for high-temperature water separation. However, the relatively high
      flow rate of the eluent required by standard high-performance liquid
      chromatography columns causes instability of the FID. In this work, micro-bore
      columns are packed with poly(styrene-divinylbenzene) (PRP-1) or Daiso gel
      octadecylsilane-bonded phase particles. Because micro columns require low volume
      flow rates, the eluent used in high-temperature water chromatography does not
      cause instability of the FID. Separation of carbohydrates, amino acids, and other
      organic acids and bases is performed on two micro-bore columns using a homemade
      high-temperature water chromatograph with FID. Both isothermal and programmed
      temperatures are used in this work. The limit of detection and the linear range
      are also determined for amino acids tested.

PMID- 16438790
TI  - Atmospheric pressure photoionization applied to quantitation of cyproterone
      acetate in human plasma.
AB  - Cyproterone acetate [6-chloro-1beta,2beta-dihydro-17alpha-hydroxy- 3'H
      cyclopropa(1,2)-pregna-1,4,6-triene-3,20-dione acetate] is a powerful
      antiandrogen used in the treatment of women suffering from disorders associated
      with androgenization such as hirsutism and acne. A fast, sensitive, and
      robustness method is developed for the determination and quantitation of
      cyproterone acetate in human blood plasma by liquid chromatography coupled with
      tandem mass spectrometry. Cyproterone acetate is extracted from 0.2 mL human
      plasma by liquid-liquid extraction. The method has a chromatographic run of 4.5
      min, using a C18 analytical column (100- yen 2.1-mm i.d.), and the linear
      calibration curve over the range is linear from 1 to 500 ng/mL (r2 > 0.994). The
      between-run precision, based on the relative standard deviation replicate quality
      controls, is 96.2% (3 ng/mL), 97.5% (120 ng/mL), and 99.1% (400 ng/mL). The
      between-run accuracy was +/- 2.7%, 3.1%, and 4.8% for the previously mentioned
      concentrations, respectively. The method is employed in a bioequivalence study of
      two tablet formulations of cyproterone acetate (100 mg).

PMID- 16438792
TI  - Determination of seven compounds in Tang Maikang granule by high-performance
      liquid chromatography.
AB  - An accurate and sensitive high-performance liquid chromatography method is
      developed and applied to the determination of seven compounds in a kind of
      traditional Chinese medicinal preparation of Tang Maikang Granule. The method is
      performed on Hypersil C(18) column (250- x 4.6-mm i.d., 5 microm), and different
      mobile phases and detectors are selected according to the various compounds. For
      astragaloside IV, an evaporative light scattering detector (ELSD) is used with a
      gradient of methanol-water at an eluent gas rate of 2.0 mL/min, under a drift
      tube temperature of 80 degrees C. Formononetin and calycosin are also eluted by a
      gradient of methanol-water, but a photodiode array (PDA) detector is used at a
      wavelength of 254 nm for formononetin and calycosin. A PDA detector at a
      wavelength of 230 nm is used for paeoniflorin, with methanol-water (30:70, v/v)
      as the mobile phase. For danshensu and protocate chualdehyde, an eluent of
      methanol-0.5% acetic acid (12:88, v/v) is used, with PDA detection at 280 nm. For
      berberine, methanol and water containing 0.1% sodium dodecanesulphonate (SDS) and
      0.1% phosphorous acid (70:30, v/v) is employed as the mobile phase, also using a
      PDA detector, but the detection wavelength is 265 nm. The intra- and interrun
      precision (relative standard deviation) of this method is less than 5% for seven
      analytes.

PMID- 16438793
TI  - Study of the racemization observed in the amide bond forming reaction on silica
      gel.
AB  - Racemization resulting from the coupling of N-(3,5-dinitrobenzoyl)-L-leucine and
      3-aminopropyl silica gel with several amide-coupling reagents is further
      investigated in order to explain the much higher degree of racemization on silica
      gel, as compared with the similar reaction in solution. Based on experiments
      using different types of solid supports, limited pore access and surface
      microchemical environment are ruled out as the possible reason for the higher
      degree of racemization that occurred on silica gel. Steric hindrance of the solid
      support is thought to have caused the amino group to be more basic relative to
      its nucleophilicity, leading to a higher degree of racemization.

PMID- 16438795
TI  - Determination of sertraline in human plasma by high-performance liquid
      chromatography-electrospray ionization mass spectrometry and method validation.
AB  - A sensitive, simple, and specific liquid chromatographic method coupled with
      electrospray ionization-mass spectrometry (MS) is presented for the determination
      of sertraline in plasma. With zaleplon as the internal standard, sertraline is
      extracted from the alkalized plasma with cyclohexane. The organic layer is
      evaporated and the residue is redissolved in the mobile phase of methanol-10
      mmol/L ammonium acetate solution-acetonitrile (62:28:10, v/v/v). An aliquot of 20
      microL is chromatographically analyzed on a Shimadzu ODS C18 column (5 microm,
      150- x 4.6-mm i.d.) by means of selected-ion monitoring mode of MS. The
      calibration curve of sertraline in plasma exhibits a linear range from 0.5 to
      25.0 ng/mL with a correlation coefficient of 0.9998. The limit of quantitation is
      0.5 ng/mL. The intra- and interday variations (relative standard deviation) are
      less than 7.8% and 9.5% (n = 5), respectively. The application of this method is
      demonstrated for the analysis of sertraline plasma samples in a human
      pharmacokinetic study.

PMID- 16438794
TI  - Comparison of extraction techniques for extraction of bioactive molecules from
      Hypericum perforatum L. plant.
AB  - Three methods commonly used for the extraction of bioactive molecules from
      natural plant material are compared. Dried Hypericum perforatum L. plant material
      is subjected to Soxhlet extraction, extraction by ultrasonication, and
      accelerated solvent extraction. The percentage of two bioactive compounds,
      hyperforin and hypericin, in the extracts is used as a parameter for comparison
      of the extraction procedure.

PMID- 16438796
TI  - Short metal capillary columns packed with polymer-coated fibrous materials in
      high-temperature gas chromatography.
AB  - The high-temperature gas chromatographic (GC) separation of several semivolatile
      compounds is studied with a short metal capillary column packed with fibrous
      material, having a polydimethylsiloxane coating thereon. Taking advantage of the
      excellent heat-resistance of the fiber and also the combination of the surface
      deactivated metal capillary, a temperature-programmed separation up to 450
      degrees C is successfully demonstrated for the separation of polymer standard
      samples. The average molecular weight of the commercially-available polymer
      standard samples for size exclusion chromatography (SEC) is estimated by high
      temperature GC analysis and compared with the nominal value determined by a
      conventional SEC method. Although a slight deviation for the number-average
      molecular weight is observed between the GC and SEC analysis, the data for the
      weight-average molecular weight shows a good agreement in these methods. The
      results also suggest the future possibility of the fiber-packed metal capillary
      as a miniaturized GC column with an increased sample loading capacity.

PMID- 16438797
TI  - Application of thin-layer chromatography to investigate oscillatory instability
      of the selected profen enantiomers in dichloromethane.
AB  - The usefulness of thin-layer chromatography (TLC) as an efficient measuring
      technique in the studies of oscillatory trans-enantiomerization of profens from
      the S to the R configuration (and vice versa) during their storage as 70% ethanol
      solutions is demonstrated in the literature. S-(+)-ibuprofen, S-(+)-naproxen, and
      S,R-(+/-)-2-phenylpropionic acid are utilized as the test profens. It is proven
      possible to show oscillatory instability with the racemic S,R-(+/-)-2
      phenylpropionic acid also. Correctness of the TLC assessment is successfully
      confirmed by means of polarimetry. Upon these preliminary results, it is
      concluded that the most probable mechanism might embrace the keto-enol
      tautomerism because of a convenient migration of the proton from one moiety of
      the profen molecule to another in an aqueous medium. To indirectly verify this
      hypothesis, profens are stored in dichloromethane, deliberately hampering their
      ability to dissociate and to re-structure. It is obvious though that the (much
      less pronounced) electrolytic dissociation can occur in the non-aqueous media as
      well. It is shown that the non-aqueous solvent considerably suppresses, although
      they do not completely eradicate, the oscillatory trans-enantiomerization of
      profens. In view of these findings, the reports which claim a predominant
      therapeutic potential of the respective S-profens become less convincing and
      certainly need reconsideration.

PMID- 16438798
TI  - ROS as signalling molecules in T cells--evidence for abnormal redox signalling in
      the autoimmune disease, rheumatoid arthritis.
AB  - Reactive oxygen species are recognised as important signalling molecules within
      cells of the immune system. This is, at least in part, due to the reversible
      activation of kinases, phosphatases and transcription factors by modification of
      critical thiol residues. However, in the chronic inflammatory disease rheumatoid
      arthritis, cells of the immune system are exposed to increased levels of
      oxidative stress and the T cell becomes refractory to growth and death stimuli.
      This contributes to the perpetuation of the immune response. As many of the
      effective therapies used in the treatment of rheumatoid arthritis modulate
      intracellular redox state, this raises the question of whether increased
      oxidative stress is causative of T-cell hyporesponsiveness. To address this
      hypothesis, this review considers the putative sources of ROS involved in normal
      intracellular signalling in T cells and the evidence in support of abnormal ROS
      fluxes contributing to T-cell hyporesponsiveness.

PMID- 16438800
TI  - N-t-Butyl hydroxylamine regulates heat shock-induced apoptosis in U937 cells.
AB  - Heat shock may increase oxidative stress due to increased production of reactive
      oxygen species and/or the promotion of cellular oxidation events. Therefore,
      compounds that scavenge reactive oxygen species may regulate heat shock-induced
      cell death. Recently, it has been shown that the decomposition product of the
      spin-trapping agent alpha-phenyl-N-t-butylnitrone, N-t-butyl hydroxylamine
      (NtBHA), mimics alpha-phenyl-N-t-butylnitrone and is much more potent in delaying
      reactive oxygen species-associated senescence. We investigated the protective
      role of NtBHA against heat shock-induced apoptosis in U937 cells. Upon exposure
      to heat shock, there was a distinct difference between the untreated cells and
      the cells pre-treated with 0.1 mM NtBHA for 2 h in regard to apoptotic
      parameters, cellular redox status, and mitochondrial function. Upon exposure to
      heat shock, NtBHA pre-treated cells showed significant inhibition of apoptotic
      features such as activation of caspase-3, up-regulation of Bax, and down
      regulation of Bcl-2 compared to untreated cells. This study indicates that NtBHA
      may play an important role in regulating the apoptosis induced by heat shock,
      presumably through scavenging of reactive oxygen species.

PMID- 16438799
TI  - The existence and significance of a mitochondrial nitrite reductase.
AB  - The physiological functions of nitric oxide (NO) are well established. The
      finding that the endothelium-derived relaxing factor (EDRF) is NO was totally
      unexpected. It was shown that NO is a reaction product of an enzymatically
      catalyzed, overall, 5-electron oxidation of guanidinium nitrogen from L-arginine
      followed by the release of the free radical species NO. NO is synthesized by a
      single protein complex supported by cofactors, coenzymes (such as
      tetrahydrobiopterin) and cytochrome P450. The latter can uncouple from substrate
      oxidation producing O2*- radicals. The research groups of Richter [Ghafourifar P,
      Richter C. Nitric oxide synthase activity in mitochondria. FEBS Lett 1997; 418:
      291-296.] and Boveris [Giulivi C, Poderoso JJ, Boveris A. Production of nitric
      oxide by mitochondria. J Biol Chem 1998; 273: 11038-11043.] identified a
      mitochondrial NO synthase (NOS). There are, however, increasing reports
      demonstrating that mitochondrial NO is derived from cytosolic NOS belonging to
      the Ca2+-dependent enzymes. NO was thought to control cytochrome oxidase. This
      assumption is controversial due to the life-time of NO in biological systems
      (millisecond range). We found a nitrite reductase in mitochondria which is of
      major interest. Any increase of nitrite in the tissue which is the first
      oxidation product of NO, for instance following NO donors, will stimulate NO
      recycling via mitochondrial nitrite reductase. In this paper, we describe the
      identity and the function of mitochondrial nitrite reductase and the consequences
      of NO-recycling in the metabolic compartment of mitochondria.

PMID- 16438801
TI  - The acute phase protein haptoglobin and its relation to oxidative status in
      piglets undergoing weaning-induced stress.
AB  - Haptoglobin (Hp) prevents the hemoglobin driven generation of hydroxyl radicals
      and lipid peroxides. Hp can reduce the neutrophil respiratory burst and is an
      antioxidative molecule in its own right. We aimed to evaluate Hp concentrations,
      oxidative stress and antioxidative capacity in blood during weaning and to
      characterise potential relationships between these parameters. Two batches of 10
      piglets each (2 trials) weaned at the age of 27-30 days were fed a starter feed
      mix ad libitum. Blood samples were taken 1 week before weaning and at weekly
      intervals thereafter. Oxidative stress was monitored via the D-ROM system,
      antioxidative capacity was measured with the TEAC assay and Hp concentrations
      were measured by ELISA. Neutrophil phagocytic activity and oxidative burst were
      examined via flow-cytometry. Body weights were recorded weekly. Hp concentrations
      were increased in both trials post-weaning (P < 0.01); oxidative stress and
      oxidative burst were elevated in trial I (P < 0.005). In trial I, Hp and ROM
      values returned to baseline levels at 6 weeks post-weaning. The piglets in trial
      II showed respiratory symptoms and maintained elevated Hp concentrations. ROM
      values and Hp were related (r = 0.58; P < 0.01). Hp and body weight gain were
      inversely related post-weaning.

PMID- 16438802
TI  - Alleviation of free radical mediated oxidative and genotoxic effects of cadmium
      by farnesol in Swiss albino mice.
AB  - Farnesol is an isoprenoid found in essential oils of ambrette seeds, citronella
      and in various aromatic plants. Exposure to cadmium from various sources affects
      the renal system adversely and Cd is an established genotoxic agent. In the
      present study, we evaluated the antigenotoxic and antioxidant efficacy of
      farnesol against cadmium chloride (CdCl2)-induced renal oxidative stress and
      genotoxicity in Swiss albino mice. Single, intraperitoneal doses of CdCl2(5 mg/kg
      body weight) for 24 h resulted in a significant (P < 0.001) increase in
      chromosomal aberration and micronuclei formation. The oral administration of
      farnesol at two doses (1% and 2% per kg body weight) for seven consecutive days
      showed significant (P < 0.05) suppression of the genotoxic effects of CdCl2 in
      the modulator groups. To study the mechanism by which farnesol exerts its
      antigenotoxic potential, enzymes involved in metabolism and detoxification were
      estimated. CdCl2 intoxication adversely affected the renal antioxidant armory and
      increased TBARS formation and xanthine oxidase levels significantly (P < 0.001).
      Farnesol showed a significant (P < 0.001) recovery in antioxidant status viz, GSH
      content (and its dependent enzymes) and catalase activity. Farnesol pretreatment
      in CdCl2-intoxicated mice showed marked (P < 0.001) suppression of TBARS'
      formation and XO activity. Our results support the conclusion that the
      anticlastogenic effect of farnesol could be due to restoration of antioxidants
      and inhibition of oxidative damage.

PMID- 16438804
TI  - High levels of active quiescin Q6 sulfhydryl oxidase (QSOX) are selectively
      present in fetal serum.
AB  - The participation of thiol-oxidoreductases such as thioredoxin during
      implantation, embryogenesis and fetal development has been extensively studied.
      Here, we analyzed the expression of the thioredoxin superfamily enzyme quiescin
      Q6/sulfhydryl oxidase (QSOX) during development. Results show that QSOX is
      present in fetal bovine serum (4 months' gestation), but its levels decrease with
      time after birth (from P1 to P60). We also demonstrate that a sulfhydryl oxidase
      activity correlates with QSOX expression in such sera, suggesting a putative role
      in the redox modulation of developmental programs.

PMID- 16438803
TI  - Antioxidant property of an active component purified from the leaves of paraquat
      tolerant Rehmannia glutinosa.
AB  - Acteoside extracted from the leaves of Rehmannia glutinosa was examined to
      determine the mechanism(s) of its antioxidant properties. The deoxyribose assay
      system showed that acteoside has a high redox potential as electron donor, which
      generates hydroxyl radicals in an Fe3+-dependent manner similar to ascorbic acid.
      However, the antioxidant properties of acteoside differ from those of ascorbic
      acid in that the superoxide anion-mediated reduction of nitroblue tetrazolium was
      actively inhibited by acteoside but not by ascorbic acid. Acteoside protected
      cells against glucose oxidase-mediated cytotoxicity and apoptosis in a dose
      dependent manner. In addition, acteoside had immune stimulating effects, as shown
      by the acteoside-mediated increase in the level of DNA synthesis, viability, and
      cytokine secretion in mouse splenocytes. Moreover, acteoside inhibited the
      gelatinolytic activity of MMP proteins in a dose-dependent manner. Considering
      these results and the fact that acteoside is a water-soluble natural product,
      acteoside might have potential as a preventative treatment for oxidative stress
      mediated diseases and have possibilities in the cosmetic industry.

PMID- 16438805
TI  - A half-marathon and a marathon run induce oxidative DNA damage, reduce
      antioxidant capacity to protect DNA against damage and modify immune function in
      hobby runners.
AB  - This study investigated whether a 21.1 km (half-marathon) or a 42.195 km
      (marathon) run modulates DNA damage, antioxidant capacity in lymphocytes and
      plasma, and the immune system in healthy hobby runners. Ten and 12 volunteers who
      completed the Baden-Marathon race in Karlsruhe with a running distance of 21.1 km
      and 41.195 km, respectively, were assessed 10 days before and immediately after
      the finish. There was no increase in the levels of endogenous DNA strand breaks
      immediately after half-marathon or marathon races. A statistically significant
      increase in the levels of oxidative DNA damage in lymphocytes was found using
      endonuclease III but not formamidopyrimidine glycolase (Fpg). The resistance of
      DNA to oxidative damage induced by hydrogen peroxide in isolated lymphocytes was
      significantly decreased after both races. The levels of plasma antioxidants such
      as alpha-tocopherol, beta-carotene and lycopene were close to, or higher than,
      those considered optimal for reducing the risk of cardiovascular diseases and
      there were no significant changes after the races in antioxidant capacity of LDL
      (lag-time test) or plasma in ORAC, TEAC or paraoxonase assays. The number and
      percentage of granulocytes and monocytes able to generate oxidative burst were
      significantly increased after both races, but the lytic activity of NK cells was
      significantly increased at the end of the half-marathon; no effect was observed
      in the marathon runners. Thus, oxidative DNA damage in lymphocytes, decreased the
      antioxidant capacity to protect lymphocytes against DNA strand breaks and
      increased the formation of reactive species by phagocytes in well-nourished hobby
      runners indicating moderate oxidative damage during such high-intensity exercise.

PMID- 16438807
TI  - The continuing challenge of palliative care.

PMID- 16438808
TI  - Counting the cost of fast access: using discrete choice experiments to elicit
      preferences in general practice.

PMID- 16438809
TI  - Out-of-hours palliative care: a qualitative study of cancer patients, carers and
      professionals.
AB  - BACKGROUND: New out-of-hours healthcare services in the UK are intended to offer
      simple, convenient access and effective triage. They may be unsatisfactory for
      patients with complex needs, where continuity of care is important. AIM: To
      explore the experiences and perceptions of out-of-hours care of patients with
      advanced cancer, and with their informal and professional carers. DESIGN OF
      STUDY: Qualitative, community-based study using in-depth interviews, focus groups
      and telephone interviews. SETTING: Urban, semi-urban and rural communities in
      three areas of Scotland. METHOD: Interviews with 36 patients with advanced cancer
      who had recently used out-of-hours services, and/or their carers, with eight
      focus groups with patients and carers and 50 telephone interviews with the
      patient's GP and other key professionals. RESULTS: Patients and carers had
      difficulty deciding whether to call out-of-hours services, due to anxiety about
      the legitimacy of need, reluctance to bother the doctor, and perceptions of
      triage as blocking access to care and out-of-hours care as impersonal. Positive
      experiences related to effective planning, particularly transfer of information,
      and empathic responses from staff. Professionals expressed concern about
      delivering good palliative care within the constraints of a generic acute
      service, and problems accessing other health and social care services.
      CONCLUSIONS: Service configuration and access to care is based predominantly on
      acute illness situations and biomedical criteria. These do not take account of
      the complex needs associated with palliative and end-of-life care. Specific
      arrangements are needed to ensure that appropriately resourced and integrated out
      of-hours care is made accessible to such patient groups.

PMID- 16438810
TI  - Communication on end-of-life decisions with patients wishing to die at home: the
      making of a guideline for GPs in Flanders, Belgium.
AB  - BACKGROUND: Communication with patients on end-of-life decisions is a delicate
      topic for which there is little guidance. AIM: To describe the development of a
      guideline for GPs on end-of-life communication with patients who wish to die at
      home, in a context where patient autonomy and euthanasia are legally regulated.
      DESIGN OF STUDY: A three-phase process (generation, elaboration and validation).
      In the generation phase, literature findings were structured and then prioritised
      in a focus group with GPs of a palliative care consultation network. In the
      elaboration phase, qualitative data on patients' and caregivers' perspectives
      were gathered through a focus group with next-of-kin, in-depth interviews with
      terminal patients, and four quality circle sessions with representatives of all
      constituencies. In the validation phase, the acceptability of the draft guideline
      was reviewed in bipolar focus groups (GPs-nurses and GPs-specialists). Finally,
      comments were solicited from experts by mail. SETTING: Primary home care in
      Belgium. SUBJECTS: Participants in this study were terminal patients (n = 17),
      next-of-kin of terminal patients (n = 17), GPs (n = 25), specialists (n = 3),
      nurses (n = 8), other caregivers (n = 2) and experts (n = 41). RESULTS:
      Caregivers and patients expressed a need for a comprehensive guideline on
      communication in end-of-life decisions. Four major communication themes were
      prioritised: truth telling; exploration of the patient's wishes regarding the end
      of life; dealing with disproportionate interventions; and dealing with requests
      for euthanasia in the terminal phase of life. Additional themes required special
      attention in the guideline: continuity of care by the GP; communication on
      foregoing food and fluid; and technical aspects of euthanasia. CONCLUSION: It was
      feasible to develop a guideline by combining the three cornerstones of evidence
      based medicine: literature search, patient values and professional experience.

PMID- 16438811
TI  - Good end-of-life care according to patients and their GPs.
AB  - BACKGROUND: Most patients prefer to die at home, where a GP provides end-of-life
      care. A few previous studies have been directed at the GPs' values on good end-of
      life care, yet no study combined values of patients and their own GP. AIM: To
      explore the aspects valued by both patients and GPs in end-of-life care at home,
      and to reflect upon the results in the context of future developments in primary
      care. DESIGN OF STUDY: Interviews with patients and their own GP. SETTING:
      Primary care in the Netherlands. METHOD: Qualitative, semi-structured interviews
      with 20 GPs and 30 of their patients with a life expectancy of less than 6
      months, and cancer, heart failure or chronic obstructive pulmonary disease as
      underlying disease. RESULTS: Patients and GPs had comparable perceptions of good
      end-of-life care. Patients and GPs identified four core items that they valued in
      end-of-life care: availability of the GP for home visits and after office-hours,
      medical competence and cooperation with other professionals, attention and
      continuity of care. CONCLUSIONS: Future developments in the organisation of
      primary care such as the restriction of time for home visits, more part-time jobs
      and GP cooperatives responsible for care after office hours, may threaten valued
      aspects in end-of-life care.

PMID- 16438812
TI  - Palliative care in primary care: a study to determine whether patients and
      professionals agree on symptoms.
AB  - BACKGROUND: Difficulties in managing symptoms of palliative care patients at home
      have been identified, yet there has been no investigation of agreement on symptom
      assessment in primary care. Lack of agreement between patients' and primary care
      professionals' symptom assessments may be contributing to difficulties in symptom
      control. AIM: To investigate agreement on symptom assessments between patients at
      home and GPs and district nurses. DESIGN OF STUDY: Prospective, self-completed,
      structured symptom assessments. SETTING: Routine contacts with adult palliative
      care patients estimated to be in their last year of life. METHOD: Patient and
      professional symptom assessments were obtained using CAMPAS-R, a comprehensive
      and reliable measure validated for palliative care in the community. Prevalence
      of reported symptoms was calculated in patient-professional pairs. Intraclass
      correlation techniques (ICCs) and percentage agreement were used to determine how
      well symptom assessments of patients and professionals agreed. RESULTS: Anxiety
      and depression were significantly more likely to be reported by professionals,
      and GPs over-identified nausea, vomiting and constipation. Professionals assessed
      emotional symptoms as more severe than patients. Agreement on scoring of physical
      symptoms was better, although this was at least partially due to agreement on
      absence of symptoms. Unlike previous reports, pain scores recorded by doctors in
      this study, were not significantly different from patients. CONCLUSION: This
      quick and easy to complete assessment tool, CAMPAS-R, has potential for
      monitoring quality of palliative care symptom control at home.

PMID- 16438813
TI  - Involving patients in primary care consultations: assessing preferences using
      discrete choice experiments.
AB  - BACKGROUND: Shared decision making (SDM) involves patients and doctors
      contributing as partners to treatment decisions. It is not known whether or to
      what extent SDM contributes to the welfare arising from a consultation, and how
      important this contribution is relative to other attributes of a consultation.
      AIM: To identify patient preferences for SDM relative to other utility bearing
      attributes of a consultation. DESIGN OF STUDY: In parallel with a randomised
      trial in training GPs in SDM competencies and risk communication skills, a
      discrete choice experiment exercise was conducted to assess patients' utilities.
      SETTING: Twenty general practices in South Wales, UK. METHOD: Five hundred and
      eighty-four responders from 747 patients attending the randomised trial (response
      rate = 78%). All patients had one of four conditions (atrial fibrillation,
      menorrhagia, menopausal symptoms or prostatism) and attended a consultation with
      a doctor in their own practice. Patients were randomised to attend a consultation
      either with a doctor who had received no training in the study or risk
      communication training alone or SDM training alone, or both combined. RESULTS:
      Five key utility bearing attributes of a consultation were identified. All
      significantly influenced patient's choice of preferred consultation style
      (P<0.001). Larger increases in utility were associated with changes on "doctor
      listens" attribute, followed by easily understood information, a shared treatment
      decision, more information and longer consultation. Utilities were influenced by
      whether the doctor had received risk communication training alone or SDM training
      alone, or both combined, prior to the consultations. The randomised trial itself
      had identified that the communication processes of these consultations changed
      significantly, with greater patient involvement in decision making, after the
      training interventions. CONCLUSION: Shared treatment decisions were valued less
      than some other attributes of a consultation. However, patient utilities for such
      involvement appeared responsive to changes in experiences of consultations. This
      suggests that SDM may gain greater value among patients once they have
      experienced it.

PMID- 16438814
TI  - The management of children with chronic fatigue syndrome-like illness in primary
      care: a cross-sectional study.
AB  - BACKGROUND: Most studies on children with chronic fatigue syndrome (CFS)/myalgic
      encephalomyelitis (ME) have been undertaken in tertiary care and little is known
      about their management in primary care. AIM: To describe the characteristics of
      patients aged 5-19 years with CFS-like illness in primary care and to examine how
      GPs investigate and manage patients. DESIGN OF STUDY: Descriptive retrospective
      questionnaire study. SETTING: Sixty-two UK GP practices in the MRC General
      Practice Research Framework (GPRF). METHOD: One hundred and twenty-two practices
      were approached; 62 identified 116 patients consulting a GP with severe fatigue
      lasting over 3 months. Practice nurses and GPs completed questionnaires from
      medical notes and patients completed postal questionnaires. RESULTS: Ninety-four
      patients were considered by a clinical panel, blind to diagnosis, to meet the
      Oxford CFS criteria with a fatigue duration of 3 months. Seventy-three per cent
      were girls, 94% white, mean age was 12.9 years and median illness duration 3.3
      years. GPs had principal responsibility for 62%. A diagnosis of CFS/ME was made
      in 55%, 30% of these within 6 months. Fifty per cent had a moderate illness
      severity. Paediatric referrals were made in 82% and psychiatric referrals in 46%
      (median time of 2 and 13 months respectively). Advice given included setting
      activity goals, pacing, rest and graded exercise. CONCLUSIONS: Patient
      characteristics are comparable to those reported in tertiary care, although fewer
      are severe cases. GPs have responsibility for the majority of patients, are
      diagnosing CFS/ME within a short time and applying a range of referral and advice
      strategies.

PMID- 16438816
TI  - Low carbohydrate diets and diabetes control.

PMID- 16438815
TI  - Assessing the diagnostic test accuracy of natriuretic peptides and ECG in the
      diagnosis of left ventricular systolic dysfunction: a systematic review and meta
      analysis.
AB  - BACKGROUND: In 2003 the National Institute of Clinical Excellence published
      guidelines recommending the use of brain natriuretic peptide (BNP) and the
      electrocardiogram (ECG) as part of the diagnostic work up of individuals with
      heart failure. However, the guideline did not address whether one test was
      superior to the other or whether performing both tests was superior to performing
      single tests. AIM: To investigate the relative test accuracy of the ECG, BNP, N
      terminal-pro brain natriuretic peptide (NT-proBNP) and combinations of two or
      more tests in the diagnosis of left ventricular systolic dysfunction (LVSD) in
      the primary care setting. DESIGN OF STUDY: Cohort studies making within-subject
      comparisons of intervention diagnostic test(s) with reference standard results.
      METHOD: Standard systematic review methodology was followed. RESULTS: Thirty-two
      primary studies met the review inclusion criteria. Studies were of variable
      quality and highly clinically heterogeneous, therefore restricting the use of
      meta-analysis. Within these limitations BNP, NT-proBNP and the ECG all had
      similar test sensitivity (>80% in the majority of studies). Specificity of the
      three tests was not as good. Three studies directly comparing BNP and the ECG
      found no difference in sensitivity and limited support for improved specificity
      of BNP. Two studies found no difference in sensitivity and limited evidence for
      an improvement in specificity for the combination of the ECG and BNP compared to
      single tests. CONCLUSION: On the basis of existing evidence, the ECG, BNP and NT
      proBNP are useful in excluding a diagnosis of LVSD (good sensitivity). However,
      use of abnormal test results to select individuals for echocardiography may
      overwhelm services. There is currently no evidence to justify the use of one test
      over another or the use of tests in combination. The additional cost of BNP is
      not self-evidently justified by improved test accuracy. Further research is
      needed to directly compare the diagnostic performance of these tests in
      homogeneous, representative primary care populations.

PMID- 16438818
TI  - A big issue?

PMID- 16438820
TI  - Trial and error.

PMID- 16438821
TI  - Government proposes to end free health care for "failed asylum seekers".

PMID- 16438822
TI  - An insider's view of the American and UK medical systems.

PMID- 16438824
TI  - Dietary dogma.

PMID- 16438825
TI  - The "Smallwood report": method or madness?

PMID- 16438827
TI  - Should nurses prescribe?

PMID- 16438844
TI  - [Sensitivity of PTEN gene-transfected endometrial carcinoma cell line to
      doxorubicin-induced apoptosis].
AB  - OBJECTIVE: To investigate whether PTEN can increase sensitivity of Ishikawa
      cells, an endometrial carcinoma cell line, to doxorubicin. METHODS: Ishikawa
      cells transfected by PTEN gene or not were separately treated with serial
      concentrations of doxorubicin. The sensitivity of cells to doxorubicin was
      determined by MTT assay. The cells were stained with Hoechst 33258 and examined
      under fluorescence microscope to determine cell apoptosis. Immunoprecipitation
      and Western blotting analysis were performed to evaluate the effects of
      doxorubicin on phosphorylation of Bad and Akt/PKB. RESULTS: Doxorubicin induced
      cell death of the PTEN-transfected and non-transfected Ishikawa cells in a dose
      dependent manner, but the cell death was more significant in PTEN-expressing
      clones than in parental Ishikawa cells. A low concentration of doxorubicin (0.1
      micromol/L) did not affect cell apoptosis in PTEN-null Ishikawa cells, but it
      induced cell apoptosis in PTEN-expressing clones. A high concentration of
      doxorubicin (1 micromol/L) induced cell apoptosis in both cell lines. However,
      the percentage of apoptotic cells was higher in PTEN-expressing clones than that
      in parental Ishikawa cells. In the PTEN-expressing clones, expression of phospho
      Akt/PKB and phospho-Bad (Ser-136) was down regulated. Doxorubicin reduced the
      levels of phospho-Akt/PKB and phospho-Bad (Ser-136) in both cell lines, but the
      most significant reduction occurred in the PTEN-expressing clones. CONCLUSION:
      PTEN significantly enhances chemosensitivity of Ishikawa cells to doxorubicin.
      With PTEN expression, doxorubicin may exert apoptosis-induction activity by
      downregulation of the PI3k/Akt/PKB signaling pathway in Ishikawa cells.

PMID- 16438845
TI  - [Z-ajoene causes cell cycle arrest at G2/M and decrease of telomerase activity in
      HL-60 cells].
AB  - OBJECTIVE: To investigate the molecular mechanisms of Z-ajoene mitosis blocking
      and telomerase inhibitory effects on HL-60 cells. METHODS: Proliferation
      inhibition of HL-60 cell line was evaluated by MTT assay. Z-ajoene-induced
      mitotic blocking effect was investigated by flow cytometry. Immunoblotting
      analysis was used to determine cell cycle regulatory proteins. The telomerase
      activity of HL-60 cells was detected by TRAP-silver stain assay. Telomerase hTRT
      and TP1 mRNA level were determined by RT-PCR. RESULTS: Z-ajoene displayed great
      proliferation inhibiting effect on HL-60 cells. Progressive increase in the
      percentage of mitotic block at G(2)/M phase was observed from 4 h to 12 h after
      treatment with 10 micromol/L Z-ajoene, with a peak at 10 h, which was 1.95 times
      higher than that in control. Z-ajoene also caused an increase in cyclin B1
      accumulation and a decrease of p34(cdc2) expression. But Z-ajoene did not change
      the level of cyclin A. After treating with 10 micromol/L Z-ajoene for 24 h, the
      telomerase activity of HL-60 cells was also decreased in a dose-independent
      manner. Furthermore, telomerase hTRT and TP1 mRNA levels decreased after 10
      micromol/L Z-ajoene treatment for 24 h. CONCLUSION: The results suggest that Z
      ajoene has potent anti-cancer activity, and that its inhibitory effect on
      telomerase activity and on cell growth might be the result of G(2)/M phase
      blocking.

PMID- 16438846
TI  - [Amphiregulin antisense RNA expression inhibits angiogenesis of human breast
      cancer in nude mice].
AB  - OBJECTIVE: To investigate the anti-angiogenic effect of amphiregulin (AR)
      antisense RNA expression in breast cancer. METHODS: Human AR cDNA antisense
      plasmid was transfected into NS2T2A1 cells (a human breast cancer cell line). Two
      selected clones expressed AR antisense RNA (AR AS1 and AR AS3 cell lines) in
      which AR protein expression was reduced. Control cell line NS2T2A1 V was obtained
      by empty vector transfection. These cells were injected subcutaneously into nude
      mice. The effects of conditioned media on proliferation of human microvascular
      endothelial cells (HMEC) were evaluated and VEGF secreted by the cells was
      measured by ELISA method. In tumor tissues, VEGF expression levels were measured
      by quantitative RT-PCR, and CD31-immunostaining was used for intra-tumoral
      vascular quantification. RESULTS: The proliferation index of HMEC cells grown in
      conditioned media with AR AS1 and AR AS3 was significantly reduced in comparison
      with that of control cells, accompanied by a decreased VEGF secretion. In tumors
      derived from AR AS1 and AR AS3 cells, intra-tumoral vascularization was reduced
      to about 50% of that derived from control cell line, accompanied with a decrease
      of VEGF expression. CONCLUSION: Amphiregulin antisense RNA expression inhibits
      efficiently the angiogenesis in breast cancer, suggesting this growth factor
      could represent a novel therapeutic target in breast cancer.

PMID- 16438847
TI  - [Effect of a hypothetical gene Af116609 on multi-drug resistance of gastric
      cancer cells].
AB  - OBJECTIVE: To investigate the effect of gene Af116609 on gastric cancer multi
      drug resistance (MDR) by introducing it into gastric cancer multi-drug resistant
      (MDR) cell line SGC7901/VCR. METHODS: Gene Af116609 was cloned from SGC7901/VCR
      by RT-PCR and its differential expression between gastric cancer MDR cells and
      its parental cells was displayed by Northern blot. The gene was introduced to
      gastric cancer cells by transfection of recombinant eukaryotic expression vector
      by electroporation. MTT assay in vitro was applied to investigate its effect on
      multi-drug resistance phenotype of gastric cancer cells. RESULTS: The full length
      CDS of gene Af116609, as long as 327 bp, was cloned from gastric cancer MDR cell
      line SGC7901/VCR and its sequence was coincident with the hypothetical gene
      Af116609 in GenBank. It was overexpressed in MDR cells than its parental cells at
      mRNA level. In the MTT assay in vitro, the drug sensitive cells transfected with
      sense eukaryotic expression vector showed upregulated targeted gene, with
      increased resistance to vincristine, 5-fliorouracil and arabinoside, and
      decreased resistance to adriamycin, but no influence on resistance to
      methotrexate. However, the drug resistant cells transfected with anti-sense
      eukaryotic expression vector, showed down regulated targeted gene, with less
      resistance to all the five anticancer drugs to different degrees. CONCLUSION:
      Gene Af116609 is related to MDR phenotype of gastric cancer cells and may become
      a candidate molecular target to reverse the MDR of gastric cancer.

PMID- 16438848
TI  - [Detection of multidrug-resistance proteins with protein array chips].
AB  - OBJECTIVE: To evaluate the use of protein array chips in detection of multidrug
      resistance proteins. METHODS: Human erythroleukemic cell line K562 and its
      doxorubicin-resistant counterpart K562/A02 were used in the study. Monoclonal
      antibodies against P-glycoprotein (P-gP), multidrug resistance-associated protein
      (MRP1) and breast cancer resistance protein (BCRP) were immobilized onto agarose
      film-coated glass. The antibody-cell binding was assessed by capturing K562 and
      K562/A02 cells. The protein array was observed under a microscope and the image
      was captured with a CCD camera. The expression levels of the three proteins were
      also measured by flow cytometry (FCM). RESULTS: The expression of P-gP and BCRP
      in K562 was very low. However, MRP1 expression was high. P-gP and MRP1 were
      highly expressed in K562/A02, while the expression of BCRP was low. FCM results
      showed that the expression rate of P-gP, MRP1 and BCRP in K562 cells was 5.98% +/
      2.19%, 95.80% +/- 3.98%, 1.03% +/- 0.45%, respectively, while that in K562/A02
      cells was 92.67% +/- 1.80%, 97.18% +/- 1.02%, 3.98% +/- 0.37%, respectively. The
      results of protein array method are consistent with those of FCM (P > 0.05).
      CONCLUSION: It is feasible to develop a new protein array technique and to
      provide a novel method for multi-drug resistant cell detection, with a high
      throughput, high specificity, simple procedure and low cost.

PMID- 16438849
TI  - [Transcription factor Sp1 expression in gastric cancer and its prognostic value].
AB  - OBJECTIVE: To investigate the expression of transcription factor Sp1 in human
      gastric cancer tissues and normal gastric mucosa, and its prognostic
      significance. METHODS: By using immunohistochemistry, we studied the Sp1
      expression patterns in 65 cases of gastric cancer with various clinico-pathologic
      characteristics, and 40 normal gastric mucosa specimens obtained from patients
      who underwent partial gastrectomy for benign gastric diseases. The significance
      of Sp1 expression on the survival of patients was evaluated. RESULTS: The
      expression rate of Sp1 in normal gastric mucosa was 12.5% (5/40). The positively
      stained glandular cells were mainly limited to those in the neck region. Cells at
      the basal portion of the gland were essentially negative. In sharp contrast, Sp1
      expression rate in gastric cancer lesions was 53.8% (35/65). The medium survival
      time in patients who had a tumor with negative, weak and strong Sp1 expression
      was 1700, 1560 and 1026 days, respectively (P = 0.036). Sp1 protein expression
      was closely related to the depth of tumor invasion and TNM stage (P = 0.001, P =
      0.026), but not related to the number of metastatic lymph nodes and Lauren's
      classification (P = 0.306, P = 0.667). CONCLUSION: Normal and malignant gastric
      tissues have unique Sp1 expression patterns. Sp1 might be served as an
      independent prognostic factor.

PMID- 16438850
TI  - [The expression of 11 cancer/testis (CT) antigen genes in esophageal carcinoma].
AB  - OBJECTIVE: To investigate the expression status of 11 different cancer/testis
      (CT) antigen genes in esophageal carcinoma. METHODS: Esophageal carcinoma tissue
      and adjacent normal esophageal mucosa taken from 35 esophageal carcinoma patients
      were assayed for the expression of 11 different CT antigen genes by RT-PCR
      techniques. RESULTS: Of the 11 CT antigen genes analyzed, none of them was
      expressed in normal esophageal mucosa. MAGE-3 was found to be the most frequently
      expressed in esophageal carcinoma tissues (62.9%), followed, in the order of
      expression frequency, by MAGE4 (31.4%), LAGE-1 (28.6%), MAGE-1 (25.7%), CT10
      (20.0%), NY-ESO-1 (20.0%), CT7 (5.7%) and SCP1 (2.9%). No expression of SSX-1,
      SSX-2 and SSX-4 was found. Among the 35 cases, 28 (80.0%) expressed at least one
      CT antigen gene, 21 (60.0%) expressed more than 2 CT antigen genes, and 4 of the
      21 (19.0%) expressed more than 4 CT antigens, which accounted for 11.4% of total
      number of patients (4/35). No CT antigen expression was found in the tumor tissue
      in 7 cases, including 5 cases in stage II and 1 case each in stage I and IV,
      respectively. Of the 11 CT genes examined, expression of 5 genes (NY-ESO-1, LAGE
      1, MAGE-1, MAGE-3 and MAGE-4) was correlated with tumor progression. SCP-1 and
      CT10 expression was found more frequently in early stage patients. With
      progression of the disease, the frequency of co-expression of multiple CT antigen
      genes was significantly increased reaching 28.6% in stage III patients.
      CONCLUSION: Of the 11 different CT antigen genes examined by RT-PCR in esophageal
      carcinoma, 8 genes were detected in various frequencies in 28 of the 35
      esophageal cancer patients studied. They are candidate tumor-associated antigens
      in the preparation of tumor vaccines for immunotherapy in esophageal cancer
      patients.

PMID- 16438851
TI  - [Correlation between blood flow velocity of feeding arteries and microvessel
      density of hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the correlation between the mean of time blood flow
      velocity (TVmean) of feeding artery around hepatocellular carcinoma (HCC) and the
      microvessel density (MVD) in relation to tumor cell differentiation, and to
      evaluate the usefulness of TVmean as a noninvasive preoperative marker of
      biologic characteristic of HCC. METHODS: To measure TVmean of feeding arteries
      around the HCC in 45 patients before operation and TVmean of minute arteries in
      hepatic tissue in 45 normal subjects by ultrasonographic examination. Tumor cell
      differentiation grade was determined by routine histopathological staining. Tumor
      MVD was measured by immunohistochemical staining with monoclonal antibodies
      against F VIII RAg of excised HCC. Correlationship between TVmean of feeding
      arteries and MVD of HCC was studied. RESULTS: A linear correlation between TVmean
      of feeding arteries around the tumors of HCC and MVD of HCC tissue (r = 0.794, y
      = 18.2764 + 1.5544x) was obtained. With TVmean > or = 21.3 cm/s, the positive and
      negative predictive values of poorly differentiated HCC were 97.4% and 87.5%,
      respectively. With TVmean < 21.3 cm/s, those of well differentiated HCC were
      88.5% and 97.3%, respectively. The degree of reliability of calculating HCC cell
      differentiation according to TVmean was 89.5%. CONCLUSION: Tumor growth and
      cellular differentiation, the two major factors affecting prognosis of HCC, may
      be evaluated by TVmean of feeding arteries around the tumor. It offers a useful
      preoperative information for predicting prognosis of HCC patients.

PMID- 16438852
TI  - [Detection of methylation of hMSH2 gene promoter region of esophageal cancer].
AB  - OBJECTIVE: To detect methylation in promoter region of hMSH2 gene in esophageal
      cancer. METHODS: Specimens of cancer and normal tissues freshly removed from 32
      cases of esophageal cancer patients without previous radiotherapy, chemotherapy
      or other treatment were preserved at -80 degrees C within 30 min. Methylation
      specific PCR (MSP) was used to detect methylation of mismatch repair gene (MMR)
      hMSH2 in promoter region in esophageal cancer and normal esophageal tissues.
      RESULTS: The frequencies of methylation of hMSH2 gene in promoter region of
      cancer and normal esophageal tissues were 32.4% (11/32) and 0/30 (0%),
      respectively, and significant difference was found between the two groups (P <
      0.01). The frequency of methylation in elder patients (> or = 70 years old) was
      significantly higher than that in younger patients (< 70 years old) (P < 0.05).
      Methylation was less frequently found in grade I-II (18.2%) than in grade III-IV
      (70.0%) (P < 0.05). CONCLUSION: Methylation of hMSH2 gene in promoter region is
      related to patients' age and histopathological grade of the esophageal cancer.

PMID- 16438853
TI  - [Clinical significance of plasma fibrinogen level in patients with colorectal
      cancer].
AB  - OBJECTIVE: To investigate correlation of plasma level of fibrinogen with clinical
      stage, depth of invasion and metastasis of colorectal cancer, and its diagnostic
      and prognostic significance. METHODS: The present study included 229 patients
      suffering from colorectal cancer and 31 cases with benign colorectal diseases.
      For each patient, plasma fibrinogen was determined by COULTER ACL-200 automated
      coagulation analyzer. The tumor markers CEA, CA19-9 and CA72-4 were examined by
      electrochemiluminescence immunoassay on Roche Eleccsys 2010 analyzer. Tumor
      makers CA242 and TPS were tested by ELISA. RESULTS: The fibrinogen level was
      increased in patients with colorectal cancer compared to that in patients with
      benign colorectal diseases. It increased with the clinical stage and depth of
      tumor invasion. The fibrinogen level was higher in patients with lymph node
      metastasis than those without. It was highest in patients with distant
      metastasis. There were positive correlations of fibrinogen level with tumor
      makers CEA, CA242 and TPS, but not with CA19-9 and CA72-4. CONCLUSION: Plasma
      fibrinogen is significantly increased in colorectal carcinoma patients with
      progression of the disease.

PMID- 16438854
TI  - [Significance of galectin-3 and CD44v6 expression in differential diagnosis of
      thyroid nodules].
AB  - OBJECTIVE: To investigate the difference of galectin-3 and CD44v6 expression
      between benign and malignant thyroid nodules, and to evaluate their clinical
      value in distinguishing thyroid cancer from benign thyroid nodules. METHODS: The
      expression of galectin-3 and CD44v6 was immunohistochemically detected by the ABC
      method in 143 benign and malignant thyroid nodule samples. RESULTS: Expression of
      these two markers in benign thyroid nodules: galectin-3 was negative in 10 cases
      of para-cancer normal tissue and 14 cases of benign nodules found in the other
      benign thyroid disease. It was weakly positive in 4 of 52 nodular goiter (7.7%).
      Also it was weakly positive in 2 of 22 follicular adenomas (9.1%). But all three
      eosinophilic follicular adenomas were diffusely or focally positive for galectin
      3. CD44v6 was negative in 10 cases of para-cancer normal tissue, but positive in
      4 of 14 nodular lesions found in benign thyroid diseases (28.6%). It was also
      positive in 16 of 52 nodular goiters (30.8%), and weakly positive in 7 of 22
      follicular adenomas (31.8%). The two markers in malignant lesions: galectin-3 was
      positive in 50 of 52 thyroid adenocarcinoma (96.2%), CD44v6 was positive in 42 of
      52 thyroid adenocarcinoma (80.8%). The positive rate of galectin-3 and CD44v6
      expression in thyroid cancer was significantly higher than that in benign thyroid
      nodule and normal tissue (P < 0.001). The sensitivity, specificity and accuracy
      of galectin-3 combined with CD44v6 in differentiating benign from malignant
      thyroid nodule were 80.8%, 93.4%, 88.8%; they were 96.2%, 90.1%, 92.3% for
      Galectin-3 alone. CONCLUSION: The immunohistochemical expression of galectin-3
      and CD44v6 by the ABC method is significantly higher in thyroid cancers than in
      benign thyroid nodules, especially galectin-3 in thyrocyte being helpful in
      differentiating benign thyroid nodule from thyroid cancer.

PMID- 16438855
TI  - [Comparison of clinical and surgico-pathological TNM stage of 2007 lung cancer
      patients].
AB  - OBJECTIVE: An accurate clinical TNM staging of lung cancer is essential for the
      precise determination of the extent of the disease in order that an optimal
      therapeutic strategy can be planned. This is especially true in patients with
      marginally resectable tumors. Clinical over-staging of the disease may deny a
      patient the benefit of surgery, whereas under-staging may oblige a patient to
      accept a fruitless or even harmful surgery. We aimed to analyze preoperative
      clinical (c-TNM) and postoperative surgico-pathologic staging (p-TNM) of lung
      cancer patients in order to evaluate the accuracy of our clinical staging and its
      implications on the surgical strategy for lung cancer. METHODS: We did a
      retrospective comparison of c-TNM and p-TNM staging of 2007 patients with lung
      cancer surgically treated from January 1999 to May 2003. Preoperative evaluation
      and c-TNM staging of all patients were based on physical examination, laboratory
      studies, routine chest X-ray and CT scan of the chest and upper abdomen. Other
      examinations included sputum cytology, bronchoscopy, abdominal ultrasonography,
      bone scintiscan, brain CT/MRI, and mediastinoscopy whenever indicated. RESULTS:
      In the present study the comparison of c-TNM and p-TNM staging of 2007 patients
      with lung cancer revealed an overall concurrence rate of only 39.0%. In the
      entire series the extent of disease was clinically underestimated in 45.2% and
      overestimated in 15.8% of the patients. Among all c-TNM stages the c-IA/B stage
      of 1105 patients gave the highest rate (55.2%) of underestimating the extent of
      disease. Clinical staging of T subsets was relatively easy with an overall
      accuracy rate of 72.9%, while that of N subsets was relatively more difficult
      with an overall accuracy rate of 53.5%. Analysis also showed that c-IV stage may
      not be an absolute contraindication to surgery, because in half of the patients,
      c-M1 turned out to be p-M0, providing the possibility of resectional surgery
      depending on the status of T and N. CONCLUSION: For reasons to be further
      determined, the present preoperative clinical TNM staging of lung cancer remains
      a crude evaluation. Further efforts to improve its accuracy are needed.

PMID- 16438856
TI  - [Long-term results of 84 surgically treated patients with extrahepatic bile duct
      carcinoma].
AB  - OBJECTIVE: Extrahepatic bile duct carcinoma is a rare but dismal malignacy. This
      study is conducted to show retrospective review and analysis of the correlation
      between the prognosis and different treatment modalities. METHODS: The data of 84
      such patients treated by different modalities from January, 1992 to July, 2000
      were retrospectively reviewed and analyzed using SPSS 10.0 statistical package.
      The survivals were estimated by the Kaplan-Meier method and the difference among
      groups was tested by the log-rank test. The prognostic factors were determined by
      Cox multivariate analysis. RESULTS: Of the 84 patients, 33 had complete
      resection, 19 palliative resection, 12 exploration alone, and the remaining 20
      were treated by chemotherapy and/or radiotherapy. The mean follow-up time was 592
      days. The overall 5-year survival rate was 13.1%. The 1-, 3- and 5-year survival
      rate following complete resection was 76.8%, 52.6% and 30.5% respectively, which
      was significantly higher than those of palliative surgery or
      chemotherapy/radiotherapy (P < 0.01). Multivariate analysis revealed that lymph
      node status (P = 0), histopathological grade (P = 0.001) and distant metastasis
      (P = 0.002) were significant high risk factors. CONCLUSION: The prognosis of
      extrahepatic bile duct carcinoma remains poor even after complete resection as
      shown to have a 5-year survival of 30.5%. More effective adjuvant therapy is
      needed. Extended resection may be helpful in improving the prognosis for
      carefully selected patients. Early diagnosis and early treatment is still the key
      to improve the long-term survival of extrahepatic bile duct carcinoma.

PMID- 16438857
TI  - [Value of mixed embolus transarterial chemoembolization in the treatment of
      hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the value of transarterial chemoembolization (TACE)
      using mixed emboli for hepatocellular carcinoma (HCC). METHODS: 188 patients with
      HCC were divided into two groups according to the treatment modality: 103
      patients in group A treated by routine iodine embolus agent; 85 patients in group
      B by mixed iodine embolus agent (ultra-liquified iodinized oil + gelatin sponge +
      chemotherapeutic agents). The pattern of the arrested iodine deposition in the
      tumor, response, resectability during follow-up, pathological changes, survival
      and complications in the two groups were analyzed and compared. RESULTS: The
      pattern of full-and-dense iodine deposition in the tumor and the response rate
      (CR + PR) were 59.2% and 32.0% in group A, 89.4% and 56.5% in group B. Surgical
      resection after TACE was possible in 5.8% (6/103) of group A versus 15.3% (13/85)
      of group B. Complete tumor necrosis was observed in 1.0% and 4.7% in groups A and
      B, respectively. 1-, 2- and 3-year actual survival rates were 57.7%, 42.8% and
      8.4% in group A, and 79.8%, 55.3%, 38.5% in group B. The difference in results
      between the two groups was statistically significant, however, the incidence of
      complication in the two groups was similar. CONCLUSION: Transarterial
      chemoembolization with mixed iodine emboli is more effective than with the
      routine iodine emboli in the treatment of bulky or nodular hepatocellular
      carcinoma rich in blood supply. Mixed iodine emboli is tolerable without increase
      in severe complications.

PMID- 16438858
TI  - [Prognostic factors and outcome of esthesioneuroblastoma].
AB  - OBJECTIVE: To investigate the clinical feature, prognostic factors and the
      appropriate treatment modality of esthesioneuroblastoma (ENB). METHODS: The data
      of 49 patients with ENB treated from Dec. 1978 to Dec. 2001 were retrospectively
      reviewed and analyzed. In this series, 3 patients had modified Kadish stage A
      disease, 15 stage B, 22 stage C, and 9 stage D lesion. The treatment modalities
      included surgery alone in 4 patients, and radiotherapy alone in 11, surgery plus
      radiotherapy in 19, radiotherapy plus chemotherapy in 8, surgery plus
      radiotherapy plus chemotherapy in 7. Statistic analysis was performed using
      software SPSS 10.0. Overall survival (OS) and disease free survival (DFS) were
      calculated using Kaplan-Meier method. Differences between survival curves were
      tested by Log rank method. RESULTS: The 5-year OS and DFS of the whole group was
      60.5% and 41.9%, respectively. The 5-year OS of patients with modified Kadish
      stage A or B disease and those with stage C or D was 78.4% and 49.7% (chi(2) =
      2.10, P = 0.15), and the 5-year DFS was 47.1% and 38.4% (chi(2) = 0.08, P =
      0.78), respectively. The 5-year OS of patients with or without neck lymph nodal
      metastasis was 17.8% and 70.8% (chi(2) = 2.32, P = 0.13), and the 5-year DFS was
      0 and 53.4% (chi(2) = 11.67, P < 0.01), respectively. For patients with kfs > or
      = 80 and those with kfs < 80, the 5-year OS was 69.0% and 30.1% (chi(2) = 7.01, P
      < 0.01), and 5-year DFS was 46.7% and 24.9% (chi(2) = 6.37, P = 0.01),
      respectively. As regard to the treatment modality, The 5-year OS was 69.7% for
      the patients treated with combined modalities and 46.3% for those with surgery
      alone or radiotherapy alone (chi(2) = 3.49, P = 0.06), and the 5-year DFS were
      52.2% and 21.8% (chi(2) = 7.03, P < 0.01), respectively. The 5-year OS was 71.1%
      for patients who received surgical treatment and 44.6% for those without it
      (chi(2) = 7.99, P < 0.01), and 5-year DFS was 54.0% and 24.1% (chi(2) = 6.41, P =
      0.01), respectively. The 5-year OS and DFS of 11 patients who received
      radiotherapy alone were 47.7% and 30.7%, respectively. For 19 patients treated by
      radiotherapy with radical purpose (including patients who received combined
      modality with radiotherapy plus chemotherapy), the 5-year OS were 33.9% for < 70
      Gy patients and 48.0% for > or = 70 Gy (chi(2) = 0.89, P = 0.35), and the 5-year
      DFS was 13.3% and 33.3% (chi (2) = 4.48, P = 0.03), respectively. For those who
      received chemotherapy or not, the 5-year OS was 50.0% and 64.9% (chi(2) = 0.91, P
      = 0.34), and the 5-year DFS was 38.9% and 43.1% (chi(2) = 0.01, P = 0.91),
      respectively. CONCLUSION: Esthesioneuroblastoma is more prevalent in the young
      male adults than female, usually with locally advanced stage lesion when first
      diagnosed. Performance status and neck lymph node metastasis are significantly
      correlated with the prognosis. Combined treatment modality consisting of surgery
      may help to gain more favorable result. Radiotherapy plays an important role in
      the management of the disease.

PMID- 16438859
TI  - [Diagnostic value of dual-head 18F-FDG imaging in metastatic lesion with unknown
      primary tumour].
AB  - OBJECTIVE: To investigate the diagnostic value of dual-head (18)F
      fluorodeoxyglucose ((18)F-FDG) imaging in metastatic lesion with unknown primary
      tumour (UPT). METHODS: Seventy patients with UPT underwent dual-head (18)F-FDG
      imaging after iv (18)F-FDG 1.85 MBq/kg. The primary tumour was diagnosed
      according to the FDG uptake and T/N value. RESULTS: Of the 70 patients, the
      primary tumour was identified by positive FDG imaging and finally confirmed
      pathologically in 58 patients (82.9%), and 12 patients had a negative FDG imaging
      (17.1%). Forty-two of the 58 positive patients were found to have lung cancer
      (72.4%). Among the 12 negative patients, their primary tumour was then identified
      by other diagnostic procedures in 5 patients (41.7%), in 1 patient, the primary
      site was detected during follow-up, however, the primary tumour was never
      detected in the rest 6 patients. CONCLUSION: Dual-probe (18)F-FDG imaging is a
      simple, quick, non-invasive and sensitive technique with an accuracy over 80% in
      the diagnosis of unknown primary tumour. The lung is found to be the most
      frequent primary site. Dual-probe (18)F-FDG imaging can be recommended as the
      first diagnostic choice for UPT.

PMID- 16438860
TI  - [Experience of gemcitabine plus cisplatin chemotherapy in 52 patients with head
      and neck cancer].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of combination chemotherapy
      using gemcitabine plus cisplatin for recurrent and/or metastastic head and neck
      cancer patients. METHODS: Fifty-two patients with recurrent or metastatic head
      and neck cancer were treated by gemcitabine 1000 mg/m(2) on D1, 8 and cisplatin
      25 mg/m(2) on D1 approximately 3 every 21 days as one cycle. RESULTS: Of 52
      assessable patients, 3 (5.8%) showed complete response and 19 (36.5%) partial
      response with an overall response rate of 42.3% (22/52). Median time to
      progression was 5.0 months, and 1-year survival was 43.4% with a median survival
      time of 9.9 months. Of 32 previously treated patients by cisplatin-containing
      regimen, 2 patients (6.3%) gave complete response and 11 (34.4%) partial response
      with an overall response rate of 40.6% (13/32). Median time to progression was
      3.4 months, and 1-year survival was 29.2% with a median survival time of 8.3
      months. Toxicity mainly included grade 1/2 myleosuppression, rash and
      nausea/vomiting. CONCLUSION: Gemcitabine plus cisplatin chemotherapy is safe and
      effective for patients with recurrent and/or metastastic head and neck cancer.

PMID- 16438861
TI  - [Preliminary results of three-dimensional conformal radiotherapy for small-cell
      lung cancer].
AB  - OBJECTIVE: To evaluate the feasibility, therapeutic effects and complications of
      three-dimensional conformal radiotherapy (3DCRT) for small-cell lung cancer
      (SCLC). METHODS: The data of 19 SCLC patients treated between June 2001 and
      August 2003, with 3DCRT were reviewed and analyzed. Eighteen patients were
      treated by radiotherapy plus chemotherapy while only 1 patient by radiotherapy
      alone. Radiotherapy was delivered at 2 Gy/fraction, 5 fractions per week with a
      median total dose of 54 Gy. Chemotherapy consisted of 4 - 6 cycles of etoposide
      and cisplatin or carboplatin. The median follow-up time was 24 months. RESULTS:
      (1) The overall response rate after 3DCRT was 79.0%, with a complete remission
      rate of 31.6% (6/19), partial remission rate of 47.4% (9/19). The 1- and 2-year
      overall survival (OS) was 71.7% and 35.8% respectively, with a median survival
      time (MST) of 19 months, and both the 1- and 2-year local progression free
      survival (LPFS) were 94.7%. (2) Of these 19 patients, grade 2 acute radiation
      pneumonitis developed in 5.3%, grade 2 late radiation pneumofibrosis in 5.3%,
      grade 2 acute radiation esophagitis in 10.5% and grade 2 acute hematologic
      toxicity in 10.5%. CONCLUSION: Three-dimensional conformal radiotherapy is
      feasible in the treatment of SCLC with high response rate and acceptable
      complications. Further observation, more patients treated by 3DCRT and prolonged
      follow-up are needed to evaluate remote survival.

PMID- 16438862
TI  - [Current status of the study of the mechanism of epidermal growth factor receptor
      targeting drug therapy and their related markers].

PMID- 16438863
TI  - [DNA damage and repair ].

PMID- 16438864
TI  - [The effect of antisense survivin-liposome complex on cell growth, apoptosis and
      cell cycle in hepatocellular carcinoma cells].
AB  - OBJECTIVE: To investigate the effects and the mechanisms of cell growth
      inhibition in hepatocellular carcinoma cells after induction with antisense
      survivin-liposome (LIP) complex, and to provide evidence in treatment for
      hepatocellular carcinoma and tumors expressing survivin. METHODS: Survivin ODNs
      was transfected into HepG2 cells mediated by LiP reagent. The expression of
      survivin mRNA and protein was detected by RT-PCR and Western blot. MTT assay was
      applied to determine cell proliferation in HepG2 cells. Active caspase-3 and
      apoptosis rate were evaluated by flow cytometric analysis. The morphological
      changes were assessed by electron microscopy. Cell cycle was analyzed by flow
      cytometry in the cell cycle-synchronized hepatocellular carcinoma cells treated
      with the antisense compound. RESULTS: Antisense compound efficiently down
      regulated survivin expression (mRNA and protein) in a dose-dependent manner with
      an IC(50) of 250 nmol/L. Its maximal effect was achieved at a concentration of
      600 nmol/L, when expression levels were down-regulated by 80%, as revealed by
      gradually increase of caspase-3-like protease activity and apoptosis rate in a
      time-dependent manner. Morphological apoptotic changes such as membrane blebbing,
      loss of microvilli, cytoplasmic vasculization, condensation of cytoplasm and
      nucleus, chromatin fragmentation, and apoptosis and cell growth inhibition were
      observed. In the cell cycle-synchronized hepatocellular carcinoma cells,
      antisense compound induced cell cycle arrest followed by apoptosis. After treated
      with low concentration of compound, the cell cycle was arrested at S phase or
      G2/M phase; while at high concentration, the cell cycle was mainly arrested at S
      phase. Apoptosis was obviously observed and the rate of apoptosis was increased
      in a time and concentration-dependent manner. CONCLUSION: Antisense survivin has
      significant inhibitory effect on growth of hepatocellular carcinoma cells in
      vitro. This is associated with cell cycle arrest and apoptosis.

PMID- 16438865
TI  - [Mechanisms of sensitization by 8-chloro-adenosine of human tumor cells to TRAIL
      induced apoptosis].
AB  - OBJECTIVE: To study the effect of 8-chloro-adenosine (8-Cl-Ado) on the
      sensitivity of human hepatoma and breast cancer cell lines to TRAIL-induced
      apoptosis in vitro and its mechanisms. METHODS: Recombinant soluble TRAIL
      (rsTRAIL) or 8-Cl-Ado was used to treat hepatoma cell line BEL-7402 and breast
      cancer cell line MCF-7 in vitro. MTT assay was used to evaluate cell viability.
      The effect of cotreatment with rsTRAIL and 8-Cl-Ado was analyzed. NF-kappaB
      activity reporter plasmid was designed to measure the activity of transcription
      factor NF-kappaB. After transient transfection with the reporter plasmid, which
      contains NF-kappaB-responsive elements, into the cell lines, cells were treated
      with rsTRAIL and/or 8-Cl-Ado, then the activity of the reporter gene luciferase
      was determined. Different kinds of caspase inhibitors were used to measure the
      effect of caspases in the rsTRAIL and/or 8-Cl-Ado induced apoptosis. RESULTS: 8
      Cl-Ado could greatly enhance sensitivity of BEL-7402 and MCF-7 cells to reTRAIL.
      Treatment with 8-Cl-Ado and rsTRAIL inactivated transcription factor NF-kappaB
      and induced apoptosis in BEL-7402, but not in MCF-7. Caspase family inhibitor
      could not prevent apoptosis induced by 8-Cl-Ado and rsTRAIL in BEL-7402 cells,
      however, it could block apoptosis in MCF-7 cells, indicating that two different
      apoptosis pathways in MCF-7 and BEL-7402 might exist, one was caspase dependent
      and the other caspase independent. Moreover, all of the inhibitors of caspse-3, 
      8 and -9 could not block apoptosis induced by the co-treatment. CONCLUSION: 8
      chloro-adenosine can enhance the sensitivity of human hepatoma cell line BEL-7402
      and breast cancer cell line MCF-7 to rsTRAIL, even though MCF-7 is TRAIL
      resistant. 8-Cl-Ado combined with rsTRAIL can trigger different signal pathways
      in MCF-7 and BEL-7402, which are caspase dependent and independent, respectively.

PMID- 16438866
TI  - [Inhibitory effect of tumor suppressor gene PTEN on hepatocellular carcinoma cell
      line HHCC proliferation and its mechanisms of action].
AB  - OBJECTIVE: To study the effect of tumor suppressor gene PTEN on proliferation and
      cell cycle of hepatocellular carcinoma cell line HHCC. METHODS: Firstly,
      eukaryotic expression vectors of wild type and mutated type of PTEN gene were
      constructed, named as pEGFP-WT-PTEN and pEGFP-PTEN; G129R, respectively.
      Lipofectamine 2000 was used to transfect the constructed expression vectors into
      hepatocellular carcinoma cell line HHCC which was PTEN protein negative. G418 was
      used to select the cell clones constantly expressing PTEN protein. Flow cytometry
      was used to assay the cell cycle of HHCC transfected by above mentioned
      eukaryotic expression vectors and non-transfected cell line HHCC. Intrinsic 473
      phosphorylated AKT representing the level of active AKT was assayed by Western
      blot. The non-transfected HHCC served as control. RESULTS: The proliferation of
      HHCC constantly expressing PTEN protein was obviously inhibited compared with
      HHCC cells transfected with mutated PTEN gene and empty vectors, and non
      transfected HHCC cells. The number of HHCC cells transfected with wild type PTEN
      gene at G(1) phase, G(2) phase and S phase was 70.8%, 6.8% and 22.4%,
      respectively. Compared with control group transfected with empty vector, the
      number of G(1) phase HHCC cells constantly expressing wild type-PTEN protein was
      significantly higher than that of control. The number of cells in G(2) and S
      phase was significantly lower than that of control. However, the number of cells
      in G(1) phase, G(2) phase and S phase of HHCC transfected with mutant PTEN was
      63.2%, 10.1% and 26.7%, respectively. There was no significant difference
      compared with control group. Western blot result showed that the intrinsic level
      of 473-phosphorylated AKT of HHCC constantly expressing wild type PTEN protein
      was down-regulated, and that of HHCC transfected with mutated PTEN gene was equal
      to that of control. CONCLUSION: Wild type PTEN gene can inhibit the proliferation
      of hepatocellular carcinoma cells at G(1) phase. The mechanism is possibly
      related with intrinsic activity of AKT, which is down-regulated by wild type
      PTEN.

PMID- 16438867
TI  - [Synergistic induction of apoptosis by the combination of TRAIL and low dose
      adriamycin in human osteosarcoma cell line U2OS].
AB  - OBJECTIVE: To investigate whether TRAIL can synergize with adriamycin (ADM) to
      kill osteosarcoma cells (U2OS) in vitro, and its possible molecular mechanism.
      METHODS: MTT was used to evaluate the cytotoxic effect of TRAIL and ADM either
      used alone or in combination at 24 hours after treatment to U20S cells. Cell
      apoptosis and its proportion were detected by flow cytometry assay. Acridine
      orange fluorescence microscopy and transmission electron microscopy were used to
      examine cellular and ultrastructural changes of apoptosis. The changes of cFLIP
      in mRNA and protein level were semi-quantified by RT-PCR and Western blot
      analysis. RESULTS: (1) U2OS cells were not sensitive to TRAIL (IC(50) > 1 mg/L);
      the cells were relatively more responsive to ADM in an apparent dose-effect
      fashion. (2) The combination of TRAIL and ADM presented a synergistic effect on
      U2OS cells. Subtoxic concentration of TRAIL (0.1 mg/L) combined with subtoxic
      concentration of ADM (1.0 micromol/l) killed (49.54 +/- 2.79)% of U2OS cells. (3)
      The cytotoxicity was mainly attributed to cell apoptosis as demonstrated by flow
      cytometry assay, fluorescence microscopy and electron microscopy. CONCLUSION:
      Subtoxic dose of TRAIL can effectively kill osteosarcoma cells (U2OS) in
      combination with subtoxic dose of ADM, but not effective when used alone.
      Apoptosis is the main mechanism of this killing effect induced by combination of
      TRAIL and ADM. Down regulation of cFLIP at mRNA and protein level is involved in
      this apoptosis pathway.

PMID- 16438868
TI  - [Multivariate analysis of prognosis in gastrointestinal stromal tumor].
AB  - OBJECTIVE: To identify prognostic factors in patients with gastrointestinal
      stromal tumors (GIST). METHODS: Hematoxylin and eosin (H&E) stained
      histopathological slides of tumors from patients with mesenchymal neoplasms
      growing in the gastrointestinal tract and abdomen were reviewed. Two
      histologically representative areas were identified and chosen for tissue
      microarray. Immunohistochemical staining was performed to demonstrate c-kit
      protein (CD117), CD34, smooth muscle actin, desmin and S-100 protein. The
      relations of various clinicopathologic features to outcome were analyzed.
      RESULTS: The overall disease-specific survival of 194 patients was 93.5% at 1
      year, 72.1% at 3 years and 63.2% at 5 years. Univariate analysis indicated that
      the tumor size, mitotic count, primary location, necrosis, high cellularity,
      mucosal invasion, mixed cell type, hemorrhage, direct tumor invasion of
      surrounding tissue, male sex, incompleteness of resection, cytologic atypia were
      significant predictors of survival. Multivariate analysis showed that tumor size,
      mitotic count, necrosis, direct tumor invasion of surrounding tissue and male sex
      were poor prognostic signs. CONCLUSION: Tumor size and mitotic count are
      important prognostic factors. However, to evaluate the prognosis of these tumors,
      a surgical pathologist should incorporate multiple parameters into their
      histologic evaluation in attempt to reach an appropriate opinion on the
      aggressiveness of GIST.

PMID- 16438869
TI  - [A prognostic scoring system for preoperative prediction of lymph node metastases
      in gastric cancers].
AB  - OBJECTIVE: To establish a preoperative scoring system to predict the lymph node
      metastases (N) in gastric cancers. METHODS: The clinicopathologic data of 291
      cases with gastric cancer were analyzed retrospectively. The factors influencing
      significantly actual lymph node status (pN) were selected through the univariate
      and the multivariate analysis, and the score of each factor was identified.
      Scores predicting different N stages were identified using receiver operating
      characteristic curves. The N stages defined by the score system were compared
      with the actual pN status using kappa statistics and diagnostic test. RESULTS:
      Tumor size, depth of invasion and histopathological types were selected to
      establish the scoring system. According to this score system, scores 0-4 predict
      N0, scores 5-7 predict N1, scores 8-9 predict N2 and scores 10-13 predict N3.
      There was a good agreement between N stages predicted by the scoring system and
      the actual pN status (weighted kappa = 0.605, u = 14.548, P < 0.0001). The crude
      agreement, positive predictive value and negative predictive value of the scoring
      system were 82.8%, 65.6% and 88.5%, respectively. CONCLUSION: The scoring system
      can provide accurate and reliable information to predict the lymph node
      metastases of gastric cancers preoperatively. It is simple and practical to use
      in clinical work and can help surgeons to choose an optimal extent of lymph node
      dissection for gastric cancer.

PMID- 16438870
TI  - [The relationship between 99mTc-MIBI scintimammography of breast cancer and
      multidrug-resistant proteins].
AB  - OBJECTIVE: To evaluate the relationship between the clearance rate of technetium
      99m methoxyisobutylisonitrile ((99m)Tc-MIBI) in scintimammography and multidrug
      resistant proteins expression in breast cancer tissues. METHODS: Seventy-six
      patients with breast cancer underwent (99m)Tc-MIBI scintimammography before
      treatment, and static planar images were taken at 10 min and 180 min after
      scintimammography. The clearance rate of (99m)Tc-MIBI was calculated in each
      patient. Immunohistochemical analysis was performed on pathological specimens of
      the 76 breast tumors to determine the expression of P-glycoprotein (P-gp),
      glutathione S-transferase Pi (GST-pi) and topoisomerase II (Topo II). RESULTS:
      The clearance rate was significantly higher in 36 patients with positive P-gp
      expression when compared with that in 40 patients with negative P-gp expression.
      There was no significant relationship between GST-pi, Topo II and the clearance
      rate of (99m)Tc-MIBI. CONCLUSION: The clearance rate of (99m)Tc-MIBI in breast
      imaging may be used to evaluate the P-gp level in breast cancers.

PMID- 16438871
TI  - [Investigation of bile duct injury after transcatheter arterial
      chemoembolization].
AB  - OBJECTIVE: To investigate the image findings of bile duct injury after
      transcatheter arterial chemoembolization (TACE) for hepatic malignancy. METHODS:
      During the past 3 years, 1240 patients with different hepatic malignancies had
      undergone a total of 2680 TACE procedures. Eighteen patients (1.4%) developed
      bile duct injuries from 3 weeks to 3 months after TACE. All of the 18 patients
      received follow-up CT and ultra-sonography, 14 MRI and 15 digital subtract
      angiography (DSA). The image data was retrospectively reviewed, with the
      potential predisposing factors correlated to TACE-induced bile duct injury.
      RESULTS: TACE-induced bile duct injuries developed in 13 of 148 patients with
      liver metastasis (8.8%), 5 of 1092 patients with hepatocellular carcinoma (HCC)
      (0.5%). On image examination, focal peripheral intrahepatic bile duct dilatation
      was detected in 4 cases, multiple bile duct dilatations with segmental or sub
      segmental distribution in 8, and a large lobular cystic lesion or biloma in 6
      cases, and progressive atrophy of the corresponding hepatic parenchyma in 6
      patients in whom the TACE induced-bile injury developed at different intervals
      after TACE. The incidence of bile duct injury was higher in non-cirrhotic
      patients with metastatic liver lesions than in patients with hepatocellular
      carcinoma associated with cirrhosis (P < 0.01), and it was also higher in
      patients using an emulsion of lipiodol-cisplatin or carboplatin than in patients
      using other emboliging agents (P < 0.01). The incidence was higher either in
      patients with hypovascular lesions than in patients with hypervascular lesions (P
      < 0.05). CONCLUSION: Biliary abnormalities, including focal and multiple
      intrahepatic bile duct dilatation, and cystic lesion or biloma, may develop and
      can be detected during the follow-up examination imaging in patients with hepatic
      malignancy after TACE. Noncirrhotic liver and intact function, due to the lack of
      peri-biliany collateral circulation, are the significant predisposing factors to
      the development of TACE-induced bile duct injury.

PMID- 16438872
TI  - [Prognostic factor of primary liver cancer treated by hypofractionated three
      dimensional conformal radiotherapy].
AB  - OBJECTIVE: To evaluate the toxicity and efficacy of primary liver cancer (PLC)
      treated by hypofractionated three-dimensional conformal radiotherapy (3DCRT) and
      investigate the prognostic factors. METHODS: Between April 1999 and August 2003,
      128 PLC patients received hypofractionated 3DCRT. According to UICC/AJCC staging
      system, there were 83 T3 patients, 45 T4, with none of them having lymph node
      metastasis. The mean value of gross tumor volume (GTV) was (458.92 +/- 429.8)
      cm(3) (6.2-2097 cm(3)). Thirty-four patients had portal vein tumor thrombosis
      (PVTT). 108 patients had Child-Pugh Grade A liver cirrhosis and 20 Child-Pugh
      Grade B liver cirrhosis. All patients received a total dose of (53.6 +/- 6.6)
      Gy/4-8 Gy per fraction/3 fractions per week. Forty-eight of these patients
      received 3DCRT combined with transarterial chemoembolization (TACE). RESULTS:
      Seven patients died within 3 months after the treatment were dismissed from the
      series. The response rate (CR + PR) was 55% (67/121). The overall 1-, 2-, and 3
      year survival rate was 65.0%, 43.3%, and 33.1%, respectively. T stage (P =
      0.001), GTV (P = 0.0001), PVTT (P = 0.0001) and Child-Pugh Grade (P = 0.0001) had
      significant impact on the overall survival. However, only GTV and Child-Pugh
      Grade were independent significant prognostic factors by Cox-regression analysis,
      (P = 0.044 and P = 0.015). CONCLUSION: T stage, GTV, PVTT and Child-Pugh Grade
      have significant impact on the overall survival in primary liver cancer patients
      treated by three-dimensional conformal radiotherapy. But only GTV and Child-Pugh
      Grade are independent prognostic factors.

PMID- 16438873
TI  - [Imaging evaluation of efficacy of radiofrequency ablation treatment for hepatic
      cancer].
AB  - OBJECTIVE: To investigate the value of B-ultrasonography, CT and MRI in the
      evaluation of efficacy of radiofrequency ablation (RFA) for hepatic cancer.
      METHODS: One hundred patients with hepatic cancer were treated by ultrasound
      guided RFA between October 1999 and September 2000. All patients had been
      examined by serum AFP, B-ultrasound, CT or MRI before and within one month after
      RFA. RESULTS: Before RFA, 34 patients who had had CT, the tumor showed hypo- or
      iso-density un-enhancement and enhancement on dynamic scanning. After RFA, 14
      patients were examined by CT scan. Compared with the density on CT scan before
      RFA, 5 patients showed lower density lesion without any enhancement on dynamic
      scanning, but the other 9 patients showed similar images to the previous CT scan
      before RFA in some parts of their tumor. Before RFA, 66 patients examined by MRI
      showed hypo-intensity on T(1)-weighted image, hyper-intensity on T(2)-weighted
      image and enhancement on dynamic scanning. After RFA, among 86 patients examined
      by MRI, 44 showed iso- or hyper-intensity on T(1)-weighted image, iso- or hypo
      intensity on T(2)-weighted image and no enhancement on dynamic scanning. But 42
      patients showed similar images to the previous MRI imaging performed before RFA
      in some parts of their tumor. CONCLUSION: Both CT and MRI can be used as imaging
      evaluation tool on the effect of radiofrequency ablation for hepatic cancer.
      However, MRI is better than CT to detect whether the tumor is necrotic or still
      partly viable after radiofrequency ablation. Patients can be regarded as
      clinically cured provided that the serum AFP declines to the normal level from
      abnormally high level and/or MRI or CT scans show a complete necrotic lesion
      after RFA.

PMID- 16438874
TI  - [Retrospective analysis of 934 nasopharyngeal carcinoma patients treated with
      conventional external beam radiotherapy alone].
AB  - OBJECTIVE: To analyze the clinical outcome of 934 primary nasopharyngeal
      carcinoma treated with conventional external beam radiotherapy alone. METHODS: 34
      patients were treated from Jan. 1, 1999 to Dec. 31, 1999. The radiation fields
      were delineated according to the CT/MRI imaging findings on disease extent. Two
      lateral opposing isocentric portals with customized blockings were used for the
      nasopharynx and upper neck. The dose delivered to tumor in the nasopharynx was 68
      70 Gy/2 Gy fraction/7 weeks. The doses delivered to the neck was 60-70 Gy/6-7
      weeks for patients with positive lymph nodes and 50 Gy/5 weeks for the patients
      with negative lymph node. RESULTS: The 1-, 2-, 3- and 4-year overall survival
      rate (OS) was 89.5%, 81.9%, 78.1% and 75.7%, and metastasis-free survival rate
      (MFS) was 84.0%, 77.2%, 74.4% and 72.0%, respectively. The 1-, 2-, 3- and 4-year
      disease-free survival rate (DFS) was 80.8%, 73.1%, 68.5% and 65.1%, and the
      relapse-free survival rate (RFS) was 95.5%, 92.7%, 90.3% and 87.3%, respectively.
      The overall failure rate was 30.9% (289/934). At the end of the radiotherapeutic
      course, the percentage of residual disease was 14.6%. The 4-year loco-regional
      recurrence and distant metastasis rates after radiotherapy were 7.2% and 9.2%
      with a median time of 19.3 months and 12.8 months. CONCLUSION: It may be helpful
      to improve radiotherapy curative effect when the target is individually designed
      through improving irradiation technique according to CT/MRI findings and by
      shortening the overall course time, enhancing irradiation dose and strictly
      implementing QA/QC measures.

PMID- 16438875
TI  - [Randomized clinical trial of percutaneous radiofrequency ablation plus absolute
      ethanol injection compared with radiofrequency ablation alone for small
      hepatocellular carcinoma].
AB  - OBJECTIVE: To compare percutaneous radiofrequency ablation (RFA) alone and RFA
      combined with percutaneous absolute ethanol injection (RFA-PEI) in the treatment
      of single hepatocellular carcinoma smaller than 5.0 cm in diameter. METHODS: From
      Jan. 2002 till Dec. 2003, eighty-six patients were put on a randomized clinical
      trial. For RFA, the American Radiotherapeutics RF 2000 machine and 3.5 cm/LEE
      VEEN + electroradiofrequency needle was introduced under ultra-beta sound guide.
      For tumor < 3 cm, the needle was left in center of tumor and for tumor > 3 cm,
      the needle was first left in situ and twisted by 180 as it was withdrawn for
      every 1 cm, till the surface border was reached. Power output was increased from
      20 W and raised by 10-20 W per minute until the impedance became rapidly raised
      and the output decreased. Forty-five patients were treated with RFA-PEI and 41
      with RFA, with each group divided into group A (diameter < or = 3.0 cm) and group
      B (diameter = 3.1-5.0 cm) according to tumor size. The overall and local
      recurrence-free survival was used to evaluate the treatment effect. RESULTS:
      There was no mortality or serious morbidity in either group. The 6-, 12-, 18-, 24
      month survival rate of RFA-PEI and RFA was 88.9%, 84.0%, 80.6%, 73.9% and 87.7%,
      78.3%, 73.7%, 61.4% (P = 0.6181), respectively; and the local recurrence-free
      survival rates was 95.4%, 95.4%, 87.8%, 73.7% and 94.9%, 72.7%, 68.4%, 57.1% (P =
      0.0393), respectively. The local recurrence-free survival rate in group A was
      95.7%, 95.7%, 79.1%, 79.1% and 92.3%, 83.2%, 81.3%, 65.9% (P = 0.3679),
      respectively; while in group B was 95.0%, 95.0%, 95.0%, 72.6% and 100.0%, 58.3%,
      45.4%, 45.4% (P = 0.0440). CONCLUSION: Percutaneous radiofrequency ablation
      combined with percutaneous absolute ethanol injection is safe, and more effective
      and easily practiced than percutaneous radiofrequency ablation alone in the
      treatment of small hepatocellular carcinoma, especially when the tumor is greater
      than 3 cm in diameter, for which RFA-PEI may be able to reduce local recurrence
      and improve long-term survival.

PMID- 16438876
TI  - [Evaluation of transcatheter arterial chemoembolization in the prevention of
      postoperative recurrence in 1630 patients with hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate postoperative transcatheter arterial chemoembolization
      (TACE) in the prevention of postoperative recurrence of hepatocellular carcinoma
      (HCC). METHODS: In TACE group, 987 HCC patients without any evidence of
      recurrence at the first TACE were treated by prophylactic TACE postoperatively
      within one or two months. In the control group, 643 HCC patients were not treated
      by prophylactic TACE for comparison. The correlation between the first recurrence
      and prophylactic TACE was analyzed. RESULTS: Recurrence rate in the TACE and
      control group was 22.2% (219/987) and 61.6% (396/643) within 6 months (P < 0.01);
      78% (770/987) and 74.7% (480/643) within 12 months (P > 0.05); 88.6% (874/987)
      and 80.1% (515/643) within 18 months (P < 0.01), respectively. CONCLUSION:
      Postoperative prophylactic TACE may be able to suppress the recurrence formation
      for HCC patients with or without definite residual lesion within 6 months.

PMID- 16438877
TI  - [Determinants of long-term survival in 38 patients with carcinoma of ampulla of
      Vater treated by local resection].
AB  - OBJECTIVE: To investigate determinants of long-term survival for carcinoma of
      ampulla of Vater treated by local resection. METHODS: The clinical and
      pathological data of 38 such patients treated by local resection from 1983 to
      2003 were retrospectively analyzed. According to UICC staging system, there were
      T1 30, T2 7 and T3 1. Lymph nodes were involved in 4 during operation which was
      present in primary lesions larger than 2 cm across. All patients were treated by
      local resection. At first, external palpation was carried out to ascertain
      accessibility. Then with the duodenum opened, direct exploration was carried out.
      On deciding for resection, the common bile duct was probe explored which guided
      the circumferential ring resection 1 cm, away from the tumor, including all
      layers of duodenum, ampula and partial bile and terminal pancreatic ducts and the
      posterial wall of duodenum was completed in steps. Meticulous care was taken not
      to suture the pancreatic duct and endotheliation was ensured at the mouth of
      common bile duct and duodenum. The basal tissue was frozen sectioned to ensure
      negative stumps. The gall bladder of 6 patients was also resected. SPSS 10.0
      software was used in data processing, log-rank test used in univariate analysis
      and Cox equation for multivariate analysis and Kaplan-Meirer method for the
      survival rates. RESULTS: Thirty-eight patients received local resection giving an
      operative mortality of 0% and morbidity of 13.2%. The 1-, 5- and 10-year survival
      rate was 83.5%, 51.4%, and 38.9%, respectively, with a median survival of 3.35
      years. Up to now, 13 patients have survived for more than five years and 2
      patients beyond ten years. The tumour size, tumour grading, lymph node status and
      UICC stage were significant prognostic factors in univariate analysis. However,
      only lymph node status was a statistically independent predictor of prognosis in
      multivariate analysis. CONCLUSION: Local excision is safe giving low morbidity
      and good survival in carefully selected cases. Preferably it is indicated only in
      high risk patients with a pT1 and well differentiated ampullary cancer smaller
      than 1 cm in diameter.

PMID- 16438878
TI  - [Clinical study of zoledronic acid in the treatment of cancer-induced
      hypercalcemia].
AB  - OBJECTIVE: To investigate the effect and safety of zoledronic acid (Zoledex) in
      patients with cancer-induced hypercalcemia. METHODS: Seventeen patients with
      cancer-induced hypercalcemia (corrected blood calcium > 2.70 mmol/L) were treated
      intravenously by 4 mg zoledex within 15 minutes on the first day. The corrected
      blood calcium was observed every 4 days in the following 28 days. RESULTS: The
      response rate was 94.1% (16/17). The mean corrected blood calcium became normal
      after the first dose of zoledex (P < 0.01). The lowest value was found on the
      fourteenth day after treatment. The main side effects consisted of fever (29.4%,
      5/17), hypocalcemic tetany (11.8%, 2/17) and arythmia (5.9%, 1/17). CONCLUSION:
      Zoledex is effective and safe in the treatment of patient with cancer-induced
      hypercalcemia.

PMID- 16438879
TI  - [Treatment modalities and prognostic factors of chordoma in the skull base].
AB  - OBJECTIVE: To investigate the clinical characteristics, treatment modalities and
      prognostic factors of chordoma in the skull base. METHODS: The data of 37
      patients with chordoma in the skull base treated from 1970 to 2002 were
      retrospectively reviewed. Twenty-eighty received surgery plus radiotherapy, 8
      radiotherapy alone and 1 surgery alone. The total dose of irradiation ranged from
      30 - 75 Gy with a median of 60 Gy. RESULTS: The rates of symptom relief and
      remarkable tumor regression at the end of radiotherapy were 86.5% and 48.6%,
      respectively. The nerve and endocrine function recovery was observed in some
      patients within six months to two years after treatment. The overall 1-, 3-, 5-
      and 10-year survival were 97.3%, 87.3%, 71.5% and 41.0%, respectively. The
      overall 1-, 3-, 5- and 10-year survival were 100.0%, 92.9%, 85.7% and 50.8% in
      patients with palsies of cranial nerves II-VIII, but 100.0%, 75.0%, 45.0% and 0
      in patients with dysfunction of cranial nerves IX-XII, respectively (P = 0.04).
      CONCLUSION: Surgery is the first option for chordoma, but resection with a safe
      margin is difficult to achieve due to the special anatomical location of the
      skull base. Local failure is the main cause of death. Radiotherapy is an
      important adjuvant for local control. The total dose should not be less than 60
      Gy for prophylactic purpose, and more than 70 Gy should be given to patients with
      recurrence, residual lesions after surgery or those not operated. The injury of
      cranial nerves IX-XII suggests a poor prognosis.

PMID- 16438880
TI  - [Current status and prospect of neoplasm targeted therapy].

PMID- 16438881
TI  - [NP9 gene inhibits tumorigenicity of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To study the effect of NP9 on the growth of transplanted
      nasopharyngeal carcinoma (NPC) in nude mice and explore the mechanisms involved.
      METHODS: Recombinant pRc/CMV2-NP9 plasmid was constructed and transfected into
      the NPC cell lines by lipofectamine 2000. Cell clones stably expressing NP9 were
      obtained by detecting the mRNA expression of NP9 in G418-resistant clones with RT
      PCR. The tumorigenicity and size of transplanted tumors were assessed after
      inoculation of NPC cells and their transgene clones into Balb/C mice. The
      expression of PCNA and cyclin D1 in transplanted tumors was detected by
      immunohistochemistry. RESULTS: The expression of NP9 was detected in some of NP9
      gene-transfected G418-resistant clones of CNE1 and SUNE1. In vivo experiments
      showed that the tumorigenicity of CNE19 clone was decreased significantly
      compared to that of CNE1 and its vector control, and the transplanted tumors grew
      more slowly from SUNE1/NP9 than from SUNE1 and SUNE1/vector. Compared with the
      vector control, the expression of cyclin D1 and PCNA in CNE1/NP9 transplants was
      decreased. CONCLUSION: NP9 inhibits tumorigenicity and growth of NPC transplanted
      tumor by down-regulating the expression of cyclin D1 and PCNA.

PMID- 16438882
TI  - [Selection of the peptides specifically binding to hepatoma by using phage
      display in vivo].
AB  - OBJECTIVE: To screen the peptides binding to hepatoma specifically. METHODS: Nude
      mice were inoculated with human tumor cells BEL-7402, then the Ph.D.-12 Phage
      Display Peptide Library was injected intravenously (tail vein) into mice. After
      20 min the mice were sacrificed and the phage rescued from tumor tissues. All the
      tissues should be made an appraisal using immunohistochemistry and titering. The
      phage recovered from the tissues were amplified and purified then re-injected for
      next round screening. After screening for 3 rounds in vivo, the phage-peptides
      that homed to the tumor tissues or cells were obtained. Then these phage clones
      were sequenced to analyze the motif. All the sequenced clones were appraised by
      using cell ELISA and titering the distribution in vivo. RESULTS: Through the
      appraisal from vivo and vitro and peptides' sequences, several target motifs were
      preliminarily determined. CONCLUSIONS: Some phage-peptides which could
      specifically bind tumor cells or tissues can be selected successfully from the
      random twelve-peptide library by means of phage display in vivo.

PMID- 16438883
TI  - [Expression of IgVH and B7-1 in proteome of the human colorectal carcinoma cell
      lines].
AB  - OBJECTIVE: To conduct a proteomic analysis of human colorectal carcinoma cell
      lines LS174T and SW480 by two-dimensional electrophoresis (2-DE) and matrix
      assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS). METHODS: The total proteins of human colorectal carcinoma cell lines LS174T
      and SW480 were separated with 2-DE using immobilized pH gradient strips and
      analyzed by MALDI-TOF-MS to obtain peptide mass fingerprints (PMFs). Proteins
      were identified by using Mascot software to search protein databases. RESULTS:
      Good resolution 2-DE maps were obtained. Some proteins including immunoglobulin
      heavy chain variable region (IgVH) and co-stimulatory molecule B7-1 were
      identified. IgVH and B7-1 were confirmed by electrospray ionization tandem
      spectrometry (ESI-MS/MS) and immunocytochemistry. CONCLUSION: There are IgVH and
      B7-1 expressions in human colorectal carcinoma cell lines LS174T and SW480.
      Results obtained will help to elucidate the mechanisms of tumor immune escape.

PMID- 16438884
TI  - [An anti-P-gp/anti-CD3 bispecific antibody cytotoxic to human multidrug resistant
      KB cells].
AB  - OBJECTIVE: To study the specific cytotoxicity mediated by anti-P-gp/anti-CD(3)
      diabodies in multidrug resistant solid tumor using P-gp as target. METHODS: The
      anti-P-gp/anti-CD(3) diabodies were secreted from E. coli strain 16C9 containing
      the expression plasmid PAYZDCP, grown at 30 degrees C in a shaker flask; the
      diabodies were purified by affinity chromatography and identified by SDS-PAGE;
      the effect of the anti-P-gp/anti-CD(3) diabody mediated lysis of P-gp-expressing
      tumor cells was assayed by (51)Cr release assay in vitro, and by human KB nude
      mouse xenograft models in vivo. RESULTS: The diabodies were generated by bacteria
      as a soluble functional form and purified by one-step affinity chromatography
      with a yield > 4 mg/L culture medium. In (51)Cr release assay, the diabodies
      targeted human activated T cells to lyse P-gp(+)-KB/MDR cells in a dose-dependent
      manner. It suggested that the diabody was able to induce an efficient lysis of
      the target cells by human T cells in vitro. When combined with activated human T
      cells, the diabody significantly inhibited the growth of KB/MDR, but had no
      effect on KB xenografts. CONCLUSION: The anti-P-gp/anti-CD(3) bispecific antibody
      is a potent agent for targeting human T lymphocytes to lyse solid tumor cells
      overexpressing P-gp in vitro and in vivo.

PMID- 16438885
TI  - [Hypermethylation of promoter region of RASSF1A gene in ovarian malignant
      epithelial tumors].
AB  - OBJECTIVE: To investigate hypermethylation of promoter region of RASSF1A and its
      relationship with ovarian malignant epithelial tumors. METHODS: Methylation
      specific PCR (MSP) was used to determine the hypermethylation of promoter region
      of ras association domain family 1 (RASSF1A) gene in 80 cases of ovarian
      malignant epithelial tumors. RESULTS: No methylation of promoter region of
      RASSF1A gene was found in all 80 normal control tissues (0). Of 80 ovarian
      malignant epithelial tumors 42 were hypermethylated in promoter region of RASSF1A
      gene (52.5%). There was no statistically significant difference in the frequency
      of hypermethylation of RASSF1A gene among serious adenocarcinomas, mucinous
      adenocarcinomas and endometrioid adenocarcinomas (54.2%, 52.4% and 45.5%,
      respectively; P > 0.05). Hypermethylation of RASSF1A gene happened more often in
      tumors in stage III and IV (66.7% and 77.8%) than that in stage I and II (21.4%
      and 16.7%; P < 0.05). It was less frequently observed in well and moderately
      differentiated tumors (34.5% and 35.0%) than in poorly differentiated tumors
      (80.6%; P < 0.05). CONCLUSION: High frequency of methylation of RASSF1A promoter
      exists in ovarian malignant epithelial tumors as a tumor suppressor gene, its
      suppressor activity may be abrogated by an epigenetic mechanism. Hypermethylation
      of RASSF1A promoter in patients with epithelial malignant ovarian tumors is
      related to clinical stage and histopathological grade. It indicates poor
      prognosis.

PMID- 16438886
TI  - [Expression of cyclooxygenase-2, hMLH1 and hMSH2 proteins, and their relationship
      with microsatellite instability in gastric carcinoma].
AB  - OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2), human mut-l
      homologue 1 (hMLH1) and human mut-s homologue 2 (hMSH2) proteins in human paired
      gastric carcinoma (GC) and adjacent normal mucosa, and analyze their relationship
      with microsatellite instability (MSI). METHODS: The protein expressions were
      examined by western blotting. Five MSI loci were assessed by PCR. RESULTS: In 30
      surgically excised GC tissues, the overexpression rate of COX-2, the low
      expression rate of hMLH1 and hMSH2 were 66.7%, 40% and 33.3%, respectively.
      Significant differences were found when compared with those of adjacent normal
      mucosa (P < 0.05). MSI was detected in 13 GC. The number of MSI-H (MSI-High, > or
      = 2 loci), MSI-L (MSI-Low, only one locus), and MSS (microsatellite stable) were
      9, 4 and 17, respectively. The number of low expression rates of COX-2, hMLH1 and
      hMSH2 in MSI-H were 6, 8 and 5, respectively. There were significant differences
      compared to that of MSS (P < 0.05). CONCLUSION: The results suggest that
      microsatellite instability pathway is probably involved in the carcinogenesis of
      gastric carcinoma, which is frequently accompanied by low expression of hMLH1 and
      hMSH2, and may be also by low expression of COX-2.

PMID- 16438887
TI  - [Expression of somatostatin receptor reporter gene and its correlation with
      targeted imaging in vivo for detection of pancreas carcinoma].
AB  - OBJECTIVE: To evaluate the value of (99 m)Tc-sandostatin scintigraphy in targeted
      diagnosis of pancreas carcinoma and the correlation with expression of
      somatostatin receptor (SSTR) reporter gene in tumor tissue. METHODS: Nude mice
      bearing human pancreas carcinoma xenograft were established in advance. (99 m)Tc
      sandostatin imaging was performed in 18 nude mice and tumor to normal tissue
      ratio (T/NT) was calculated. mRNA expression of SSTR1, SSTR2 and SSTR5 in tumor
      tissue was detected by RT-PCR. RESULTS: Out of 18 nude mice, 13 mice showed
      intense uptake of (99 m)Tc-sandostatin. Six hours after (99 m)Tc-sandostatin
      administration, the T/NT ratio was 2.53 +/- 0.84. Five mice showed negative
      findings, and the T/NT ratio was 1.04 +/- 0.06. Positive correlations were
      obtained between the T/NT ratio and the expression of SSTR1 and SSTR2 mRNA,
      especially SSTR2 (r = 0.807, P < 0.01). CONCLUSION: High expression of SSTR1,
      SSTR2 and SSTR5 mRNA were found in human pancreas tumor xenograft in nude mice,
      especially SSTR2. There is a significant correlation between the tumor uptake of
      (99 m)Tc-sandostatin and SSTR2 mRNA level. This approach may allow SSTR-targeted
      diagnosis and therapy of human pancreas cancer.

PMID- 16438888
TI  - [Tea consumption and risk of biliary tract cancers and gallstone disease: a
      population-based case-control study in Shanghai, China].
AB  - OBJECTIVE: To investigate the relationship between tea consumption, biliary tract
      cancers and gallstone disease. METHODS: A population-based case-control study was
      conducted in urban Shanghai from 1 June 1997 to 31 May 2001 involving interviews
      with 627 new cases of biliary tract cancers (including 368 cases of gallbladder
      cancer, 191 cases of extrahepatic bile duct cancer and 68 cases of cancer of the
      ampulla of Vater) aged 35 to 74 years and 959 population controls frequency
      matched to cases by gender and age in five-year group. 1037 patients of gallstone
      disease were selected from the same hospital. All subjects were interviewed in
      person by trained interviewers by use of a structured questionnaire.
      Unconditional logistic regression analysis was used to calculate adjusted odds
      ratio (OR) and 95% confidence interval (CI). RESULTS: Compared with tea non
      drinkers, current tea consumption was inversely associated with risk of
      gallbladder cancer, extrahepatic bile duct cancer and gallstone disease among
      females with OR of 0.57 (95% CI: 0.34-0.96), 0.53 (95% CI: 0.27-1.03) and 0.71
      (95% CI: 0.51-0.99), respectively. OR declined with younger age at initiation of
      tea drinking and with longer duration of tea consumption (P for trend < 0.05).
      Among males, the corresponding OR were mostly below one, although not
      statistically significant. CONCLUSION: Tea consumption may decrease the risk of
      cancers of the gallbladder and extrahepatic bile duct among females. The
      protective effect appears to be independent of gallstone disease.

PMID- 16438889
TI  - [Manganese superoxide dismutase gene transfection of mouse small intestinal
      epithelial cells protects them from radiation injury].
AB  - OBJECTIVE: To investigate the protective effect of manganese superoxide dismutase
      (MnSOD) gene transfer to small intestinal epithelial cells from radiation injury.
      METHODS: Herpes simplex virus (HSV) vector containing both the human MnSOD and
      GFP genes was introduced into mouse small intestine. Expression of MnSOD by the
      intestinal villi was confirmed by nested RT-PCR, immunofluorescence and enzyme
      activity assay. Mice were then given various doses of irradiation over the
      abdomen. The height of intestinal villi was measured on histopathology sections
      by SZ-PT optical system before irradiation, 24 h and 72 h post-irradiation. All
      comparisons were performed by one-way analysis of variance using the SPSS
      statistical software to analyze the significance between groups. RESULTS: Nested
      RT-PCR, immunofluorescence and enzyme activity assay of MnSOD demonstrated
      overexpression and increased activity of MnSOD in the inoculated intestine of
      mice. Control (sham inoculated) irradiated mice showed decreased villi height by
      40.1%-59.3% on day 1 and 44.2%-65.1% on day 3 (7.5-15 Gy). Treatment of mice with
      HSV-MnSOD prior to radiation led to statistically significant radioprotection of
      the small bowel with mean villi height decreased by only 3.1%-12.4% on day 1 and
      6.3%-29.1% on day 3. CONCLUSION: The results demonstrate that overexpression of
      human MnSOD via a replication defective herpes simplex viral vector is an
      effective method to protect the small intestine from damage caused by ionizing
      radiation.

PMID- 16438890
TI  - [Plasma level and prognostic significance of VEGF, bFGF and MMP-9 in patients
      with advanced non-small-cell lung cancer].
AB  - OBJECTIVE: To measure plasma levels of VEGF, bFGF and MMP-9 in advanced non-small
      cell lung cancer (NSCLC) patients and evaluate their prognostic value. METHODS:
      The plasma levels of VEGF, bFGF and MMP-9 in 46 cases with advanced NSCLC were
      measured by ELISA before chemotherapy and in 30 cases after chemotherapy.
      RESULTS: The plasma levels of VEGF, bFGF and MMP-9 in patients before
      chemotherapy were significantly higher than those in healthy control persons (P <
      0.05). The correlation between plasma levels of VEGF and bFGF was significant,
      Spearman's r = 0.329 (P = 0.027). No correlation was found among the levels of
      angiogenic factors studied above and the following clinical parameters such as
      age, sex, histological subtype, differentiation of tumor cells, TNM-stage and
      also blood leukocyte, hemoglobin and platelet counts. The plasma level of MMP-9
      in patients with extensive metastasis (including bone metastasis) was
      significantly higher than that in patients with bone metastasis only (P = 0.013).
      Reduction of plasma bFGF level after chemotherapy was a unique independent good
      prognostic factor (RR = 11.737, P = 0.02). CONCLUSION: The measurement of plasma
      levels of such angiogenic factors as VEGF, bFGF and MMP-9 in advanced NSCLC is
      helpful for prediction of metastasis tendency and evaluation of prognosis.

PMID- 16438891
TI  - [A prospective multicenter clinical trial of breast conserving therapy for early
      breast cancer in China].
AB  - OBJECTIVE: To demonstrate the feasibility of breast conserving therapy (BCT) and
      establish a multimodality BCT model for early breast cancer in China. METHODS: A
      prospective multicenter case control study consisting of 4461 patients was
      carried out by the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS)
      and nine other hospitals across China from November, 2001 to November, 2004, the
      result of BCT and mastectomy on early stage breast cancer were compared. Patients
      entry-primary tumor < or = 3 cm, primary tumor in periphery quadrant, pathology
      showed infiltrating carcinoma and clinical absence of locoregional lymphatic or
      distant metastasis. Patients rejection-multiple center cancer or diffused
      malignant calcified spots, previous radical radiation therapy in the chest,
      accompanying collogenolytic vascular granuloma and simultaneous pregnancy.
      RESULTS: Of these 4461 patients, breast conserving surgery was performed in 872
      (19.5%) patients who were eligible for BCT, accounting for 9.0% of all operated
      breast cancer patients during the same period. The rates of local recurrence,
      metastasis and death were 1.0% (9/872), 1.3% (11/872) and 0.1% (1/872) in BCT
      group, versus 0.5% (18/3589), 1.4% (49/3589) and 0.1% (4/3589) in the mastectomy
      group. No statistical significant difference was found between these two groups
      (P > 0.05). Cosmetic evaluation of breast in BCT group was carried out
      postoperatively at points of six months, one year and two years with 89.7%, 91.1%
      and 86.6% of the patients assessed as excellent or fine cosmetic state
      respectively. CONCLUSION: Breast conserving therapy for early stage breast cancer
      is feasible in China, with no ominous effect on the survival and recurrence rate.
      Breast conserving therapy is able to improve not only the quality of life but
      also enhance the confidence of the patients, in addition to quasi-perfect
      cosmetic results. Standard comprehensive BCT involving multi-centers all
      concentrating on combination treatment should be widely adopted in China in the
      future. However, breast conserving surgery should selectively be used only for
      early stage breast cancer, and should be combined with postoperative
      radiotherapy, chemotherapy and hormone therapy in order to guarantee success.

PMID- 16438892
TI  - [Partial laryngectomy for ninety-eight patients with glottic carcinoma of the
      larynx].
AB  - OBJECTIVE: To investigate the therapeutic results after various kinds of partial
      laryngectomy for patients with glottic carcinoma of the larynx. METHODS: From
      January 1980 to Mar 2004, 98 patients with glottic carcinoma of the larynx were
      treated by various kinds of partial laryngectomy. The types of operation varied
      according to stage of the lesion: vertical or frontovertical partial laryngectomy
      for T1b, T2 and T1a with invasion of anterior commissura, Tuker's operation or
      supracricoid partial laryngectomy for T1b, T2 or those with invasion of over half
      of contralateral cord, and extended vertical partial laryngectomy with resection
      of arytenoids for T3, or with invasion of ipsilateral arytenoids cartilage
      without involving postcricoid mucosa or posterior commissura. Totally, vertical
      partial laryngectomy was carried out for 76 patients, extended vertical partial
      laryngectomy for 7, supracricoid partial laryngectomy for 3 and Tucker's
      operation for 12. One stage unilateral neck dissection was performed in 5
      patients and postoperative radio-therapy was supplemented to 5 (dose 60 Gy). For
      laryngeal function restoration, pectoro-hyomyo-flap and cricohyoidoepi glotopexy
      procedures were also performed for some patients. The clinical data of these
      patients were retrospectively analyzed. RESULTS: The 3- and 5-year survival rate
      was 86.5% (64/74) and 81.7% (49/60), respectively. The total decannulation rate
      was 94.9% (93/98), though fifteen patients had had symptoms of aspiration.
      Swallowing function of all patients recovered to the normal level. The phonation
      of all patients was restored to various degrees and they were able to communicate
      socially. CONCLUSION: The 3- and 5-year survival rates of partial laryngectomy
      for patients with glottic carcinoma of the larynx are comparable to the results
      achieved by total laryngectomy, but the quality of life of the patents much
      better. Complete resection of the tumor and simultaneous preservation of
      respiratory and vocal function whenever possible by partial laryngectomy is very
      important for improving patients' life quality. With a suitable size and good
      blood supply, the sternohyoid muscle flap of unipedical and half-thickness
      instead of whole thickness is ideal in the reconstruction of laryngeal defect
      after vertical partial laryngectomy.

PMID- 16438893
TI  - [Investigation of CT guided percutaneous incisional needle biopsy in
      parapharyngeal region for suspicious nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the safety and efficacy of percutaneous incisional
      needle biopsy (PINB) in the parapharyngeal region under CT guide for highly
      suspicious nasopharyngeal carcinoma (NPC) or recurrence of NPC after
      radiotherapy. METHODS: PINB under CT guide was performed in 32 highly suspicious
      NPC or recurrence of NPC after radiotherapy through three puncture routes:
      posterolateral maxillary sinus fatty area, mandibular fossa area, and anterior
      mastoid area. Specimens were fixed by 95% alcohol and then underwent pathologic
      examination. RESULTS: CT guided PINB was successfully performed in every patients
      with a technical successful rate of 100%. Definitive histopathologic diagnosis
      was obtained in 30 patients: squamous-cell carcinoma 21, undifferentiated
      carcinoma 5 and adenocarcinoma 4. The remaining two negative cases were confirmed
      as fibrosis after radiotherapy. Complications included persistent bleeding of
      puncture point in one patient and bloody sputum in 3 patients which subsided
      after symptomatic management. None of these patients was found to have symptoms
      of nerve injury caused by PINB procedure. CONCLUSION: The CT guided percutaneous
      incisional needle biopsy in parapharyngeal region through the above three
      puncture routes for highly suspicious nasopharyngeal carcinoma is safe, rapid and
      effective.

PMID- 16438894
TI  - [Triple-phase helical CT in the differential diagnosis between small
      hepatocellular carcinoma and small hepatic cavernous hemangioma].
AB  - OBJECTIVE: To scrutinize the enhancement pattern at hepatic arterial phase (HAP),
      portal venous phase (PVP) and delayed phase (DP) by helical CT examination in
      order to differentiate small hepatocellular carcinoma (SHCC) from small hepatic
      cavernous hemangioma (SHCH). METHODS: In 38 patients (41 lesions) with SHCC and
      35 patients (45 lesions) with SHCH, the images at HAP, PVP and DP were recorded
      as to the characteristic of enhancements with the average CT value at the HAP
      monitored and compared. RESULTS: The enhancement patterns of SHCC at the HAP,
      PVP, and DP were assessed as hyper-hypo-hypodense in 20 lesions, hyper-iso
      hypodense in 6 lesions, hyper-hyper-hypodense in 3 lesions, hyper-iso-isodense in
      5 lesions, iso-hypo-hypodense in 3 lesions, and hypo-hypo-hypodense in 4 lesions.
      The enhancement patterns of the SHCH were assessed as a peripheral hyperdense
      nodular at HAP, then progressively enlarged at PVP and turned into a isodense or
      homogeneous hyperdense nodular at DP in 27 lesions, hyper-hyper-iso or hyperdense
      in 9 lesions, hyper-iso-isodense in 3 lesions, hypo-hypo-hypodense in 6 lesions.
      The enhancement CT values at the HAP of homogeneous hyperdense SHCC and SHCH were
      (40.4 +/- 15.5) Hounsfield Unit (HU) and (102.8 +/- 18.9) HU respectively (P <
      0.01). CONCLUSION: Most of the small hepatocellular carcinoma and small hepatic
      cavernous hemangioma have typical appearance by triple-phase helical CT
      examination, and can easily and properly be diagnosed. But it is difficult to
      distinguish SHCC from SHCH with atypical appearance in isolated cases. Hence
      differentiation may be difficult. Therefore, further examinations such as MRI,
      ultra-sonography or isotope scintigraphy are helpful in the differential
      diagnosis.

PMID- 16438895
TI  - [Chronomodulated chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid for
      advanced gastric cancer].
AB  - OBJECTIVE: The combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and
      folinic acid (FA), being one of the effective regimens for advanced gastric
      cancer, is used in form of chronomodulated chemotherapy for advanced gastric
      cancer to investigate its efficacy and safety. METHODS: Twenty-six patients
      received a 4-day chronomodulated infusion of L-OHP, 5-Fu and FA. L-OHP (25 mg.m(
      2).d(-1)) infused from 10:00 am to 22:00 pm, and followed by 5-Fu (600 mg.m(
      2).d(-1)) and FA (300 mg.m(-2).d(-1)) from 22:00 pm to 10:00 am for 4 days using
      a multichannel programmable pump, every 2 weeks as an cycle for at least 2
      cycles. RESULTS: Twenty-six patients with previously untreated advanced gastric
      cancer were eligible. Two complete and 13 partial remissions were observed with
      an overall response rate of 57.7%. Stable disease was observed in 6 patients
      (23.1%) and progressive disease in five (19.2%). Four of these patients underwent
      surgery. The median remission time was 3.5 months and time to tumor progression
      (TTP) was 4.5 months. The median overall survival time was 8 months. A total of
      80 cycles were given without any grade 4 toxicity observed, but grade 3
      thrombocytopenia (1.3%) and mucositis (1.3%) in one patient, two grade 3
      neutropenia (2.5%) and nausea/vomiting (2.5%) in 2. CONCLUSION: Chronomodulated
      intravenous chemotherapy of oxaliplatin, 5-fluorouracil and folinic acid is
      effective and safe in the treatment of advanced gastric cancer.

PMID- 16438896
TI  - [Border-line smooth-muscle tumor of the uterus: analysis of 131 patients].
AB  - OBJECTIVE: To investigate whether the border-line uterine smooth-muscle tumor is
      different from leiomyoma or leiomyosarcoma in history and clinical
      manifestations. METHODS: The medical records of 131 surgically treated patients
      suffering from the so-called cellular leiomyoma or mitotically active leiomyoma
      of the uterus treated from 1984 to 2002 were retrospectively reviewed. All
      pathological sections of these patients were reviewed by a senior pathologist.
      Chi-square test and Kaplan-Meier life table were used for statistical analysis.
      RESULTS: The overall 5-year survival rate of patients with the border-line
      uterine smooth-muscle tumors was 100%, however, 19.1% (24/131) of whom developed
      a late recurrence and 8 patients had repeated recurrences with a more shortened
      course and aggressive potential changes of mitosis and cellular atypia. The
      overall 5-year survival rate the patients with recurrence was 91.7%, but only
      75.0% for those with repeated recurrences. CONCLUSION: Patients with border-line
      uterine smooth-muscle tumor do possess some difference in nature from the
      leiomyoma or leimyosarcoma. Long-term follow-up is very important for these
      patients after surgery.

PMID- 16438897
TI  - [Advances in the molecular target therapy in lung cancer].

PMID- 16438898
TI  - Respiratory manifestations in amyloidosis.
AB  - BACKGROUND: Amyloidosis is a collection of diseases in which different proteins
      are deposited. Amyloid deposits occur in systemic and organ-limited forms. In
      both systemic and localized forms of the disease, lung can be involved. The aim
      of this study was to explore the different respiratory manifestations of
      amyloidosis. METHODS: Chest radiology, clinical presentations,
      bronchoscopic/laryngoscopic findings and lung function data of 59 patients with
      amyloidosis involving respiratory tract collected during January 1986 to March
      2005, were analysed. RESULTS: Of the 16 cases with localized respiratory tract
      amyloidosis, 8 had the lesions in the trachea and the bronchi, 2 in the larynx
      and the trachea, 5 in the larynx and/or the pharynx, and 1 in the lung
      parenchyma. Of 43 systemic amyloidosis with respiratory tract involvement, 3 had
      the lesions in bronchi, 13 in lung parenchyma, 33 in pleura, 8 in mediastina, 1
      in nose and 1 in pharynx. Chest X-rays were normal in most cases of
      tracheobronchial amyloidosis. CT, unlike chest X-rays, showed irregular luminal
      narrowing, airway wall thickening with calcifications and soft tissue shadows in
      airway lumen. Localized lung parenchymal amyloidosis presented as multiple
      nodules. Multiple nodular opacities, patch shadows and reticular opacities were
      the main radiological findings in systemic amyloidosis with lung parenchymal
      involvement. In pleural amyloidosis, pleural effusions and pleural thickening
      were detected. Mediastinal and/or hilar adenopathy were also a form of lung
      involvement in systemic amyloidosis. The major bronchoscopic findings of
      tracheobronchial amyloidosis were narrowing of airway lumen, while nodular,
      'tumour like' or 'bubble like' masses, with missing or vague cartilaginous rings,
      were detected in about half of the patients. CONCLUSIONS: Localized respiratory
      tract amyloidosis mostly affects the trachea and the bronchi. Chest X-rays are
      not sensitive to detect these lesions. Systemic amyloidosis often involves lung
      parenchyma and the pleura. Open lung biopsy or pleural biopsy should be performed
      for the diagnosis.

PMID- 16438899
TI  - Early use of non-invasive positive pressure ventilation for acute exacerbations
      of chronic obstructive pulmonary disease: a multicentre randomized controlled
      trial.
AB  - BACKGROUND: Respiratory muscle fatigue plays an important role in acute
      exacerbations of chronic obstructive pulmonary disease (AECOPD). In previous
      clinical studies, non-invasive positive pressure ventilation (NPPV) was proved to
      be successful only for AECOPD patients with severe respiratory failure. We
      hypothesized that, the outcomes of AECOPD would be improved if NPPV is early
      (within 24 to 48 hours of admission) administered in those patients with
      respiratory muscle fatigue and mild respiratory insufficiency, especially in
      patients without fulfilling the conventional criteria of mechanical ventilatory
      support. METHODS: A prospective multicentre randomized controlled trial was
      conducted in 19 hospitals in China over 16 months. Three hundred and forty-two
      AECOPD patients with pH > or = 7.25 and PaCO2 > 45 mmHg were recruited on general
      ward and randomly assigned to standard medical treatment (control group) or early
      administration of additional NPPV (NPPV group). RESULTS: The characteristics of
      two groups on admission were similar. The number of AECOPD patients requiring
      intubations in NPPV group was much fewer than that of the control group (8/171 vs
      26/71, P = 0.002). Subgroup analysis showed the needs for intubation in mildly
      (pH > or = 7.35) and severe (pH < 7.30) acidotic patients in NPPV group were both
      decreased (9/80 vs 2/71, P = 0.047 and 8/30 vs 3/43, P = 0.048, respectively).
      The mortality in hospital was reduced slightly by NPPV but with no significant
      difference (7/171 vs 12/171, P = 0.345). Respiratory rate (RR), scale for
      accessory muscle use and arterial pH improved rapidly at the first 2 hours only
      in patients of NPPV group. After 24 hours, the differences of pH, PaO2, scale for
      accessory muscle use and RR in NPPV group [(7.36 +/- 0.06) mmHg, (72 +/- 22)
      mmHg, (2.5 +/- 0.9)/min, (22 +/- 4)/min] were statistically significant compared
      with control group (7.37 +/- 0.05) mmHg, (85 +/- 34) mmHg, (2.3 +/- 1.1)/min, (21
      +/- 4)/min, P < 0.01 for all comparisons]. CONCLUSIONS: The early use of NPPV on
      general ward improves arterial blood gas and respiratory pattern, decreases the
      rate of need for intubation in AECOPD patients. NPPV is indicative for
      alleviating respiratory muscle fatigue and preventing respiratory failure from
      exacerbation.

PMID- 16438900
TI  - Endovascular treatment of cerebral arteriovenous malformations with Onyx
      embolization.
AB  - BACKGROUND: In the past 5 years, new treatment materials and techniques offering
      a different concept in endovascular treatment have been described for cerebral
      arteriovenous malformations (CAVMs). The aim of this study was to assess the
      endovascular treatment of CAVMs by using a liquid embolic material, Onyx (Micro
      Therapeutics. Inc., Irvine, CA, USA). METHODS: From September 2003 to September
      2004, Onyx was used to treat 22 patients with CAVMs. Ten AVMS were located in
      functional areas, 8 in deep cerebral areas, and 4 in the cerebellar hemisphere.
      The size of CAVMs was about 3 cm in diameter in 5 patients, 3-6 cm in 11, and
      more than 6 cm in 6. RESULTS: In the 22 patients, Onyx embolization was
      successful. Nidus occlusion was complete in 3 patients, > 90% in 8, > 80% and <
      90% in 6, and > 50% and < 80% in 5. Complications included transient neurological
      deficits in 2 patients, and adherence of microcatheter to the site of injection
      in 2. CONCLUSIONS: Being non-adhesiveness, Onyx is a safe and satisfactory
      embolic material in the treatment of CAVMs. But its long-term efficacy awaits
      further follow-up.

PMID- 16438901
TI  - High mechanical index post-contrast ultrasonography improves tissue structural
      display of hepatocellular carcinoma.
AB  - BACKGROUND: The advent of second generation agent-SonoVue and low mechanical
      index real-time contrast enhanced ultrasonography (CEUS) imaging have been shown
      to improve the diagnostic performance of ultrasonography in hepatocellular
      carcinoma (HCC). But no report has described the effect of high mechanical index
      (MI) post-CEUS. This study aimed to investigate the value of post-CEUS in
      displaying tissue structures of HCC. METHODS: Seventy-six HCCs in 65 patients
      were included in the study. Each patient underwent three scans, high-MI (MI: 0.15
      1.6) pre-contrast ultrasound, low-MI (MI: 0.04-0.08) CEUS with contrast agent
      SonoVue, and high-MI post-contrast ultrasound, which was performed within 3
      minutes after CEUS. The size, boundary, echogenicity, internal echotexture and
      posterior acoustic enhancement of the HCCs in the conventional scans before and
      after CEUS were evaluated. According to pathological evidence, diagnosis rates of
      pre-contrast, CEUS and post-contrast scans were determined and compared. The
      potential mechanism of post-contrast ultrasound imaging was also discussed.
      RESULTS: Compared with pre-contrast, post-contrast ultrasound showed improvement
      in image quality in most HCCs: twenty-six (34.2%) more lesions showed well
      defined margins and fourteen (18.4%) more nodules showed halo sign; twenty-three
      (30.3%) lesions demonstrated enlarged in sizes; changes in echogenicity were seen
      in 30 lesions (39.5%); eighteen (23.7%) more lesions showed heterogenecity and 20
      (26.3%) more lesions showed "mosaic" or "nodule-in-nodule" sign; twelve (15.8%)
      more lesions showed posterior acoustic enhancement. Post-contrast ultrasound
      showed increased diagnostic accuracy of 93.4% (71/76), compare with 88.2% (67/76)
      of CEUS alone. CONCLUSIONS: High-MI post-contrast ultrasound utilizes harmonic
      signals during the rupture of microbubbles, and significantly improves the
      display of echo-characteristics of HCCs in ultrasound images, which adds
      diagnostic values for CEUS. Post-contrast ultrasound could play an important role
      in tissue characterization, and may be included in CEUS protocols.

PMID- 16438902
TI  - Effects of TNF-alpha and curcumin on the expression of VEGF in Raji and U937
      cells and on angiogenesis in ECV304 cells.
AB  - BACKGROUND: To better understand the possibilities of antiangiogenic tumor
      therapy and to assess possible side effects, we investigated the effect of tumour
      necrosis factor (TNF)-alpha and curcumin on the expression of vascular
      endothelial growth factor (VEGF) in U937 and Raji cell lines and their effect on
      angiogenesis in a human umbilical vein endothelial cell (HUVECs)-derived cell
      line (ECV304), and also the relationship between Notch1 and VEGF. The aim of this
      study was to elucidate potential mechanisms controlling tumor neovascularization.
      METHODS: VEGF secreted by U937 and Raji cell lines was determined by ELISA.
      Angiogenesis was tested by network formation of endothelial cells on Matrigel.
      Levels of VEGF mRNA in U937 and Raji cells and Notch1 mRNA levels in EV304 cells
      were determined by RT-PCR. RESULTS: Secretion of VEGF by U937 and Raji cells was
      increased by TNF-alpha treatment and suppressed by curcumin (P < 0.01). The mRNA
      expression of VEGF165 and VEGF121 (containing 165 and 121 amino acid residues,
      respectively) were detected in any fractions. TNF-alpha augmented the expression
      of VEGF165 and VEGF121 mRNA and curcumin reduced the expression (P < 0.01). No
      networks or cords formed in control and curcumin groups. There was tube formation
      on matrigel in the supernatants of the Raji culture group and the supernatants
      groups treated by VEGF group and TNF-alpha in Raji cell. Notch1 mRNA was detected
      but there was no significant change in the VEGF group compared with control (P >
      0.05). CONCLUSIONS: Expressions of VEGF mRNA in U937 and Raji cells were
      increased by TNF-alpha and suppressed by curcumin. VEGF and TNF-alpha can induce
      angiogenesis, and curcumin can inhibit angiogenesis in ECV304 cells.

PMID- 16438903
TI  - Increased expression of 70 kD heat shock protein in cultured primary human
      keratinocytes induced by human papillomavirus 16 E6/E7 gene.
AB  - BACKGROUND: Heat shock protein 70 (HSP70) is expressed highly in epithelial
      tumours associated closely with human papillomavirus 16 (HPV16) infections.
      However, evidence about the direct relationship between HSP70 expression and HPVs
      infections are still lacking. In the present study, we examined the expression of
      HSP70 in keratinocytes introduced with HPV16 E6/E7 oncogenes. METHODS: Stable
      transfected cells were established by transfection of the plasmids pLXSN16E6/E7
      into cultured primary keratinocytes and subsequently selected by plasmid specific
      selection antibiotic (G418) at the required concentration. The expression of
      HSP70 in pLXSN16E6/E7 transfected keratinocytes was determined by Western blot.
      The correlation of HSP70 expression and E6/E7 transfection was further confirmed
      by doubly labelled immunofluorescent staining. RESULTS: Compared to non
      transfected keratinocytes, there was a significant trend for higher levels of
      HSP70 in pLXSN16E6/E7 transfected keratinocytes. Doubly labelled
      immunofluorescent staining experiment showed that the co-localization of HPV16
      E6/E7 and HSP70 in transfected keratinocytes was observed and increased
      expression of HSP70 was strongly associated with the transfection of HPV16 E6/E7.
      CONCLUSIONS: Our studies demonstrated increased levels of HSP70 proteins in
      keratinocytes stably transfected by HPV16 E6/E7 oncogenes. It suggests that the
      expression of HSP70 is modulated by HPV16 E6/E7 proteins, which may be involved
      in HPV16 E6/E7 induced immortalization.

PMID- 16438904
TI  - Construction and expression of a Rev-dependent TNF-R1 expressing HIV-infected
      cell injurious vectors.
AB  - BACKGROUND: Rev is necessary for exporting unspliced and incompletely spliced
      intron containing HIV mRNAs and for HIV replication. The aim of this study is to
      develop a kind of selective suicide construct that can specifically and directly
      induce HIV infected cells into apoptosis based on the high affinity of Rev and
      Rev response element (RRE). METHODS: Molecular-cloning technique was used to
      synthesis Rev dependent TNF-R1 expression construct pDM128-TNF-R1 (pT128) that
      contains RRE and TNFR1 gene. Restriction digestion, Polymerase Chain Reaction
      (PCR) and DNA sequencing were processed and the exactness and correctness of the
      inserted TNF-R1 gene in pT128 were confirmed repeatedly. The expression of pT128
      co-transfected with different combination of other plasmids by calcium phosphate
      DNA co-precipitation in Helas and by gene gun transfection in keratinocytes was
      further tested by flow-cytometry and cell counted under microscope. RESULTS: The
      new plasmid specifically expressed TNF-R1 in Helas when co-transfected with pRev
      but did not when without pRev. Indirect expression of TNF-R1 from pT128 was
      slower than the direct expression of that from Hu p60 TNFR1 in pDC302 (pT60), but
      all those pT60 or pT128 transfected cells showed apoptosis at last while TNF-R1
      was sufficiently expressed. Other kinds of Rev expression construct such as pAD8
      and a chimeric HIV vaccine also can switched on the selective expression of
      pT128. Not only Rev-dependent expression in Helas, pT128 also normally expressed
      its TNF-R1 in keratinocytes. Co-transfected with pRev or pAD8 that expressed Rev,
      pT128 expressed TNF-R1 and induced apoptosis of green fluorescent keratinocytes
      in skin explant. The number of green fluorescent keratinocytes co-transfected by
      pT128 plus pRev or pAD8 was gradually outnumbered by that co-transfected by pT128
      only. The difference was more significant after culturing for 72 hours.
      CONCLUSIONS: Rev dependent pT128 is able to selectively induce apoptosis of HIV
      infected or Rev-expressed target cells by expression of TNF-R1. The new strategy
      based on manipulation of the regulatory protein of HIV may be valuable in design
      of new HIV vaccine.

PMID- 16438905
TI  - Study on the relationship between level of CD58 expression in peripheral blood
      mononuclear cell and severity of HBV infection.
AB  - BACKGROUND: As one of the intercellular adhesion molecules, CD58 plays important
      roles in promotion of the adhesion between T cells and target cells, hyperplasia,
      activation of T cells and natural killer cells, and balance between Th1 and Th2.
      We studied the relationship between the levels of CD58 expression in peripheral
      blood mononuclear cells (PBMCs) and severity of HBV infection. METHODS: The
      levels of CD58 mRNA in PBMCs were detected using quantitative reverse
      transcription PCR. The percentage of CD58 positive cells was detected by flow
      cytometry in patients and healthy controls. RESULTS: The levels of CD58 mRNA and
      the percentage of CD58 positive cells in patients infected with HBV were
      significantly higher than that in the control. Based on severity of HBV
      infection, the patients were classified into four groups. The expression of CD58
      increased significantly in an order from mild chronic, moderate chronic, severe
      chronic to severe hepatitis groups. The levels of CD58 mRNA and the percentage of
      CD58 positive cells in PBMCs from patients with HBV infection were both
      positively correlated with serum levels of ALT and AST. CONCLUSION: The level of
      CD58 expression is related with the severity of HBV infection and the degree of
      liver damage.

PMID- 16438906
TI  - Genetic determination of osteoporosis in Chinese.

PMID- 16438907
TI  - Prognosis of microscopic polyangiitis with renal involvement: report of 60
      Chinese patients.

PMID- 16438908
TI  - Heat shock protein 70 expression in relation to apoptosis in primary bladder
      transitional cell carcinoma.

PMID- 16438909
TI  - Relationship between MDR1 polymorphism and blood concentration of cyclosporine A.

PMID- 16438910
TI  - Glucose metabolism in isolated uteri of immature rats. Influence of
      prostaglandins and nitric oxide.
AB  - We studied the contractile activity and glucose metabolism, in terms of
      production of 14CO2 from [14C] glucose, in isolated uteri of immature rats.
      Immaturity was due to age or exposure to a restricted diet. The contractile
      activity in both prepubertal groups persisted for a period of 60 minutes and fell
      when indomethacin was added to the KRB medium. The production of 14CO2 was
      greater than for adult rats and fell as a result of the addition of indomethacin.
      The metabolism of [14C] arachidonic acid showed that the percentage of
      eicosanoids released in age related immature uteri was greater than that in
      restricted diet related immature uteri. In animals that are immature as a result
      of exposure to a restricted diet, 14CO2 fell due to the effect of NAME. Sodium
      nitroprusside and L-arginine increased the production of 14CO2. This effect was
      reverted by NAME and indomethacin. Conversely, the uteri of age related
      prepubertal rats were not affected. The level of activity of nitric oxide
      synthase was higher in restricted diet related immature animals and fell
      following the addition of NS-398. We may conclude that in rats exposed to a
      restricted diet, NO and COX-2 participate in glucose metabolism whereas they
      would not be involved in age related prepubertal animals.

PMID- 16438911
TI  - Effect of supplemental calcium propionate on insulin action to blood glucose
      metabolism in adult sheep.
AB  - An experiment combining a hyperinsulinemic euglycemic clamp procedure of four
      sequential 2-h periods and an isotope dilution method of [U-13C]glucose
      determined the effect of supplemental calcium propionate on blood glucose
      metabolism during insulin and glucose infusions in adult sheep. They were fed
      lucerne hay cubes and commercial concentrate with and without supplementary
      calcium propionate (Prop and Cont diets, respectively) in a crossover design for
      each 21-day period. At the preinfusion period, blood glucose turnover rate (GTR)
      was greater (P < 0.05) for the Prop diet than for the Cont diet. Blood GTR,
      endogenous glucose production rate (EGPR) and the ratio of EGPR to blood GTR were
      greater (P < 0.01, P < 0.05 and P < 0.05, respectively) for the Prop diet than
      for the Cont diet. Blood GTR and glucose infusion rate (GIR) increased (P <
      0.001) and the ratio of EGPR to blood GTR was reduced (P < 0.01) with increased
      insulin infusion rates. The maximal GIR tended to be (P < 0.10) greater for the
      Prop diet than for the Cont diet but plasma insulin concentration at half maximal
      GIR did not differ between diets. It is suggested that in adult sheep, dietary
      propionate supplementation enhances insulin action on glucose metabolism,
      however, changes in measures of tissue responsiveness and sensitivity were not
      significant.

PMID- 16438913
TI  - Effect of duodenal infusion of trans10,cis12-CLA on milk performance and milk
      fatty acid profile in dairy goats fed high or low concentrate diet in combination
      with rolled canola seed.
AB  - The effect of t10,c12-C18:2 on milk production, and fatty acid (FA) profile of
      milk fat was studied in 8 goats infused duodenally with t10,c12-C18:2 (2 g.10 h
      1) during 3 days, followed by a 2-day infusion of skim milk (SM). The goats were
      assigned to 4 diets in a factorial arrangement constituted by low (L = 45%) or
      high (H = 65% of the diet DM) percentage of concentrate without (CS0) or with
      (CS20) rolled canola seed (20% of the concentrate DM). Milk samples were
      collected before (basal), and during the t10,c12-C18:2 and SM infusions. The
      t10,c12-C18:2 in milk fat increased from undetectable basal values to an average
      of 0.39% of total FA in the 3rd day of t10,c12-C18:2 infusion. DMI, milk yield,
      and the contents and yield of milk fat, protein, and lactose were similar between
      basal and the t10,c12-C18:2 infusion. The concentration of saturated FA with 4 to
      16C did not change during the t10,c12-C18:2 infusion, whereas C18:0 increased,
      particularly in the milk fat of the CS20 group. The t10,c12-C18:2 infusion
      increased the t10- and t11-C18:1 (except a reduction in t11-C18:1 for the H-CS20
      group), and it decreased the c9,t11-C18:2 in milk fat, particularly for the H
      CS20 group. The t10,c12-C18:2 infusion reduced the c9,t11-C18:2/t11-C18:1 ratio,
      particularly for the CS0 group. The results indicate that mammary lipogenesis in
      dairy goats was not decreased by t10,c12-C18:2, however, the desaturation of long
      chain FA appeared to be equally affected as in dairy cows. This reduction in the
      desaturase index of milk fat could have been a direct effect of t10,c12-C18:2, or
      mediated via an increase in t10-C18:1.

PMID- 16438912
TI  - Effect of a supplement rich in linolenic acid added to the diet of post partum
      dairy cows on ovarian follicle growth, and milk and plasma fatty acid
      compositions.
AB  - The objective of this study was to determine the effect of a linseed supplement
      on follicle growth, progesterone concentrations and milk and plasma fatty acids
      in dairy cows post partum. Sixteen Holstein cows were given a basal total mixed
      diet plus one of two supplements: control (C; extruded soybeans; n = 8) or
      linseed (L; extruded linseeds; n = 8). One month after calving oestrous cycles
      were synchronised (PRID). Follicle growth and milk progesterone concentrations
      were measured every 2 d over the induced oestrous cycle. Milk production
      characteristics were unaffected by treatment. The L cows lost significantly more
      BCS than the C cows (P < 0.01). Plasma insulin, glucose and urea were unaffected
      by the treatment. Plasma NEFA tended to be affected by the treatment (L > C, P =
      0.08). The proportions of 18:3n-3 in milk and plasma were increased by L compared
      to C (P < 0.001 and P < 0.01, respectively). There was an effect of dietary
      supplement on the numbers of small follicles (L < C, P < 0.05). Milk progesterone
      was unaffected by treatment. In conclusion, the increased supply of 18:3n-3 to
      the cows had only a modest effect on follicle populations and corpus luteum
      activity was unchanged.

PMID- 16438914
TI  - A protein-free diet alters small intestinal architecture and digestive enzyme
      activities in rats.
AB  - The consequences of feeding a protein-free (PF) diet, as compared to casein, on
      gut characteristics were studied in slightly energy-restricted rats fed similar
      amounts of feed for 10 d. The weight and pH of fresh digesta in the stomach were
      lower (P = 0.045 and P = 0.016). However, the weight of fresh digesta in the
      other segments and gut tissue weight were not significantly affected by the diet
      (P > 0.05). Small intestinal crypt depth, width and area were reduced by 13, 23
      and 37%, respectively (P = 0.011, P = 0.004 and P = 0.001), and villus width
      tended to be smaller (P = 0.057), with the PF diet. Villus height to crypt depth
      ratio was also lower with the PF diet in the duodenum and ileum, respectively (P
      < 0.05). Finally, the specific activities of alkaline phosphatase and
      aminopeptidase N were reduced by 36 to 38% at different sites of the small
      intestine in the rats fed the PF diet (P < 0.05). In conclusion, chronic
      consumption of a protein-free diet altered the intestinal villus-crypt
      architecture and enzyme activities in rats.

PMID- 16438915
TI  - Relationship of body condition score and blood urea and ammonia to pregnancy in
      Italian Mediterranean buffaloes.
AB  - The relationship of body condition score (BCS) and blood urea and ammonia to
      pregnancy outcome was examined in Italian Mediterranean Buffalo cows mated by AI.
      The study was conducted on 150 buffaloes at 145 +/- 83 days in milk that were fed
      a diet comprising 14.8% crude protein, 0.9 milk forage units.kg-1 dry matter and
      a non-structural carbohydrate/crude protein ratio of 2.14. The stage of the
      oestrous cycle was synchronised by the Ovsynch-TAI programme and blood urea and
      ammonia levels were assessed on the day of AI. Energy corrected milk (ECM)
      production and BCS were recorded bi-weekly. The pregnancy risk was 46.7% and was
      slightly lower in buffaloes with BCS < 6.0 and BCS > 7.5. There were no
      significant differences in ECM, urea and ammonia between pregnant and non
      pregnant buffaloes. However, pregnancy outcome was higher (P = 0.02) in buffaloes
      with blood urea < 6.83 mmol.L-1. The likelihood of pregnancy for buffaloes with
      low urea blood level was 2.6 greater than for high urea level and exposure to a
      high urea level lowered the probability of pregnancy by about 0.25. The findings
      indicate that buffaloes are similar to cattle and increased blood levels of urea
      are associated with reduced fertility when animals are mated by AI.

PMID- 16438916
TI  - Docosahexaenoic acid is selectively enriched in plasma phospholipids during
      pregnancy in Trinidadian women--results of a pilot study.
AB  - The fetal demand for docosahexaenoic acid (DHA) has to be satisfied by the
      mother. We determined the fatty acids in maternal plasma non-esterified fatty
      acid (NEFA), triacylglycerol (TAG) and phosphatidylcholine (PC), in a cross
      sectional study of non-pregnant (n = 10), pregnant (n = 19), and postpartum (n =
      9) women. There were lipid class-dependent differences in plasma polyunsaturated
      fatty acid (PUFA) concentrations between groups. During pregnancy, DHA was most
      highly enriched in PC, about 230%, with more modest enrichment for linoleic acid
      (LA) and arachidonic acid (AA), and no enrichment of alpha-linolenic acid (alpha
      LNA). There was relative enrichment of LA, AA and alpha-LNA in TAG, but not of
      DHA. There was no specific enrichment of any PUFA in the NEFA pool. These data
      accord with the suggestion that the enrichment of alpha-LNA in TAG and of DHA in
      phospholipids reflects hepatic regulation of n-3 PUFA metabolism which
      potentially enhances the delivery of DHA to the placenta.

PMID- 16438917
TI  - Effect of photoperiod length on body mass and testicular growth in the house
      sparrow (Passer domesticus) and brahminy myna (Sturnus pagodarum).
AB  - Two experiments studied the relative effects on body mass and testicular growth
      of stimulatory photoperiods applied simultaneously to two photosensitive species,
      the house sparrow (Passer domesticus) and brahminy myna (Sturnus pagodarum).
      Experiment 1 on the house sparrow consisted of two parts. In experiment 1A,
      beginning on 24 March 2002, short day pretreated sparrows were exposed for 12
      weeks to 13L: 11D (13 h light: 11 h darkness), 20L: 4D and NDL (control).
      Experiment 1B was similar to 1A except that it used sparrows that were not
      treated with short days. This experiment was repeated at three different times in
      the year. Beginning on 29 December 2002 (for 24 weeks), 26 March 2003 (for 12
      weeks) and 16 August 2003 (for 8 weeks), sparrows captured from the wild and
      acclimated to captive condition for 1 week were exposed to 13L: 11D and 20L: 4D.
      Each time, a group was maintained in NDL and served as the control. Experiment 2
      was performed on myna and used an identical protocol. Beginning on 24 March 2002,
      myna that were captured from the wild and acclimated to captivity conditions were
      exposed for 16 weeks to 13L: 11D and 20L: 4D; a group was maintained in NDL and
      served as the control. There was photostimulation and subsequent regression of
      the testes on all day lengths except in the August group of experiment 1B. The
      effect on body mass was variable. Interestingly, however, the response to 20L:4D
      was relatively smaller as compared to 13L:11D. Taken together, these results
      confirm that the two species use photoperiods in control of their reproductive
      cycle, and tend to indicate that exposure to unnatural long photoperiods may in
      fact be unfavorable and could compromise gonadal growth and development.

PMID- 16438918
TI  - Milk yield, residual milk, oxytocin and cortisol release during machine milking
      in Gir, Gir x Holstein and Holstein cows.
AB  - This study evaluated the effect of exclusive machine milking on oxytocin (OT) and
      cortisol (CORT) release, and on milk yield and residual milk in Gir (group Gir),
      Holstein (group Hol) and crossbred animals (group GirHol). Six animals from each
      group were submitted to experimental milkings. As expected, milk yield was
      significantly higher in the Hol group than in the groups GirHol and Gir, and
      group GirHol produced more milk than the Gir group. In contrast, all groups
      exhibited significant but similar levels of OT, although OT increased more
      rapidly during milking for the groups Hol and GirHol than for the Gir group. In
      addition, CORT levels measured during and after milking were significantly
      influenced by the group. The Gir group showed higher levels of CORT than the
      groups GirHol and Hol. The lower performances of the Gir breed can not be
      explained by a less efficient milk ejection reflex because all cows studied
      released enough OT and had an effective milk ejection.

PMID- 16438919
TI  - Exfoliative vaginal cytology during the oestrous cycle of West African dwarf
      goats.
AB  - The pattern of vaginal cell exfoliation during the oestrous cycle period was
      studied in cycling and non-descript West African dwarf (WAD) goats. The
      exfoliated epithelial cells were categorised into parabasal, intermediate and
      superficial and their relative occurrences were used to determine the
      reproductive status of the cycling and non-descript does. The mean cell counts of
      the epithelial and leucocyte cells were also compared between the days of cycle.
      Leucocyte and epithelial cells were present in the vaginal smears of the WAD does
      throughout the cycle. Cell counts increased sharply on days 1 and 2 after
      standing oestrus. From day 4 of the cycle, the counts fell back to the levels at
      oestrus and daily variations thereafter were not striking enough to distinguish
      between the different stages of the cycle. In the non-descript does, the
      intermediate cell dominated the majority of the smears, which is the typical
      pattern of cell exfoliation in anoestrus and peri-pubertal does. In the smears
      from cycling does, however, superficial cells were more frequently observed and
      they appeared to be associated with the proestrus, oestrus and early metoestrus
      phases of the cycle. These results indicate that the pattern of exfoliation of
      vaginal cells could be used to determine the reproductive condition and by
      extension the ovarian functioning of the WAD goats.

PMID- 16438920
TI  - Nuclear and cytoplasmic localization of interferon-tau in in vitro-produced
      bovine blastocysts.
AB  - Experiments were conducted to detect interferon-tau in bovine in vitro-derived
      blastocysts by transmission electron (TEM) and confocal microscopy. TEM showed
      the presence of IFN-tau in the cytoplasm and the nuclei of expanded blastocysts.
      Confocal microscopy similarly confirmed the presence of IFN-tau in the
      trophectoderm of blastocysts. The distribution of IFN-tau appeared variable with
      some cells showing strong labeling while others appeared to be devoid of the
      protein.

PMID- 16438921
TI  - Aging, memory and visual search.
AB  - Potential age-related differences in the memory processes that underlie visual
      search are examined in the present study. Using a dynamic, gaze-contingent search
      paradigm developed to assess memory for previously examined distractors, older
      adults demonstrated no memory deficit. Surprisingly, older adults made fewer
      refixations compared to their younger counterparts, indicating better memory for
      previously inspected objects. This improved memory was not the result of a speed
      accuracy trade-off or larger Inhibition-of-Return effects for older than for
      younger adults. Additional analyses suggested that older adults may derive their
      benefit from finer spatial encoding of search items. These findings suggest that
      some of the memory processes that support visual search are relatively age
      invariant.

PMID- 16438922
TI  - Estimating the quantitative relation between incongruent information and response
      time.
AB  - In Eriksen's flanker paradigm, participants' responses are slower and more error
      prone when task-relevant and simultaneously available task-irrelevant cues are
      incongruent. The influence of task-irrelevant information decreases as its
      distance from the task-relevant information increases. Here, we manipulated the
      quantity of task-irrelevant information while keeping the distance constant. We
      asked whether when the impact on response selection processes was stronger the
      more incongruent information was available, or whether the impact on response
      selection depended only on its presence or absence. We conducted an experiment,
      in which subjects had to discriminate the direction of motion of a central point
      light-walker that was flanked by two, four, or eight point-light-walkers at an
      equal distance from the center. The experiment showed that reaction times
      increased with the number of incongruent walkers. This effect was modulated by
      the total number of walkers, showing that the effect of incongruent information
      saturates when the display is cluttered.

PMID- 16438923
TI  - Violation of pure insertion during mental rotation is independent of stimulus
      type, task, and subjects' age.
AB  - The experiment validated and extended the finding of Ilan and Miller (1994) [A
      violation of pure insertion: mental rotation and choice reaction time. Journal of
      Experimental Psychology: Human Perception and Psychophysics 20, 520-536] that the
      mental rotation process is not purely inserted into a mirror-normal
      discrimination task. In contrast to their work we used other experimental stimuli
      (drawings of animals instead of characters), a different task (same/different
      comparison) and investigated this effect under a developmental perspective.
      Adults and children between the age of 8 and 10 took significantly longer to
      respond to upright drawings of animals in conditions containing rotated stimuli
      than in conditions containing only upright stimuli, indicating a violation of
      pure insertion. In general, we found evidence that the violation of pure
      insertion during a mental rotation task itself can be generalised across stimulus
      type, task, and subject populations. However, for children this effect was
      independent of the format of the stimuli, while for adults the effect was larger
      for mirror-imaged than for identical objects. This suggests that the violation of
      pure insertion might occur at different processing stages as a function of age.

PMID- 16438924
TI  - The influence of individual preventive measures on the clinical severity of
      malaria among Nigerian children.

PMID- 16438925
TI  - Wild isolates of Plasmodium falciparum from India show restricted polymorphism in
      T-helper cell epitopes of the circumsporozoite protein.
AB  - Genetic polymorphism in T-helper cell epitopic regions of circumsporozoite
      protein of 148 Plasmodium falciparum isolates from different epidemic and endemic
      regions of India has been analyzed by polymerase chain reaction and sequencing.
      The variation has been found to be regionally unbiased in the sense that
      identical sequence variation has been found in different regions of India. The
      variation has also been found to be restricted and could be categorized into four
      groups. Since the variation is restricted, prototype variants could be included
      in a subunit polyvalent vaccine against sporozoites.

PMID- 16438926
TI  - Sensitization to Anisakis simplex s.l. in a healthy population.
AB  - The main objective of this study was to determine the degree of sensitization to
      Anisakis simplex s.l. in healthy population. Using the determination of specific
      IgE, we studied the seroprevalence against A. simplex s.l. in blood donors
      selected at random in the region of Antequera (Southern Spain). We detected
      22.1%. The immunoblotting technique revealed a band of approximately 60 kDa in
      the serum of individuals who also exhibited high values of specific IgE against
      A. simplex s.l. This band would be useful for diagnosis.

PMID- 16438927
TI  - Flow injection analysis with diode array absorbance detection and dynamic surface
      tension detection for studying denaturation and surface activity of globular
      proteins.
AB  - In this article, a multidimensional dynamic surface tension detector (DSTD), in a
      parallel configuration with a UV-visible diode array absorbance detector, is
      presented in a novel flow injection analysis (FIA) application to study the
      effects of chemical denaturants urea, guanidinium hydrochloride (GdmHCl), and
      guanidinium thyocyanate (GdmSCN) on the surface activity of globular proteins at
      the liquid-air interface. The DSTD signal is obtained by measuring the changing
      pressure across the liquid-air interface of 4-mul drops repeatedly forming at the
      end of a capillary using FIA. The sensitivity and selectivity of the DSTD signal
      is related to the surface-active protein concentration in aqueous solution
      combined with the thermodynamics and kinetics of protein interaction at a liquid
      air drop interface. Rapid on-line calibration and measurement of dynamic surface
      tension is applied, with the surface tension converted into surface pressure
      results. Continuous surface tension measurement throughout the entire drop growth
      is achieved, providing insight into kinetic behavior of protein interactive
      processes at the liquid-air drop interface. Specifically, chemical denaturation
      of 12 commercial globular proteins-chicken egg albumin, bovine serum albumin,
      human serum albumin, alpha-lactalbumin (alpha-Lac), myoglobin, cytochrome c,
      hemoglobin, carbonic anhydrase, alpha-chymotrypsinogen A, beta-lactoglobulin
      (beta-LG), lysozyme, and glyceraldehyde-3-phosphate-dehydrogenase-is studied in
      terms of surface pressure (i.e., surface activity) after treatment with
      increasing concentrations of urea, GdmHCl, and GdmSCN in the 0-8, 0-6, and 0-5 M
      ranges, respectively. For several of these proteins, the spectroscopic absorbance
      changes are monitored simultaneously to provide additional information prior to
      drop formation. Results show that surface pressure of proteins generally
      increases as the denaturant concentration increases and that effectiveness is
      GdmSCN > GdmHCl > urea. Protein unfolding curves obtained by plotting surface
      pressure as a function of denaturant concentration are presented and compared
      with respect to unfolding curves obtained by using UV absorbance and literature
      data. Kinetic information relative to the protein adsorption to the air-liquid
      interface of two proteins, alpha-Lac and beta-LG (chosen as representative
      proteins for comparison), denatured by the three denaturants is also studied and
      discussed.

PMID- 16438928
TI  - Characterization of phospholipid-protein interactions by capillary isoelectric
      focusing with whole-column imaging detection.
AB  - The integration of functional proteins in the phospholipid bilayer is one of the
      most crucial features of biological membrane architecture. Phospholipid-protein
      interactions play an important role in the functions of bounded proteins in the
      phospholipid membrane. When the phospholipid-protein interactions occur, the
      protein structure tends to alter, which can result in a change in the isoelectric
      points (pI) of protein. Capillary isoelectric focusing (cIEF) with whole-column
      imaging detection (WCID) is an attractive technique that has the features of
      simple operation, high resolution, and fast separation without focused band
      mobility for detection of amphoteric biomolecules. In this study, a cIEF-WCID
      method was developed to characterize the phospholipids-protein interactions by
      monitoring the protein cIEF profiles. Seven proteins with different pI and
      molecular mass , and a zwitterionic phosphatidylcholine (PC) with zwitterionic
      properties, were used to evaluate the feasibility of the cIEF-WCID approach in
      the study of phospholipid-protein interactions. The cIEF profiles changed in
      response to the changes in protein conformation, clearly exhibiting interactions
      between the PC vesicles and the targeted proteins. The formation of PC-protein
      complex was observed in the cIEF electropherograms. It was demonstrated that
      seven proteins displayed distinct interactions with the PC vesicles due to their
      different chemical and physical properties. The influences of the PC
      concentration, incubation time, and incubation temperature on the phospholipids
      protein interactions were investigated. This study validated a novel analytical
      approach for the characterization of phospholipid-protein interactions.

PMID- 16438929
TI  - Validation of real-time reverse-transcription-polymerase chain reaction for
      quantification of capecitabine-metabolizing enzymes.
AB  - Capecitabine is an oral fluoropyrimidine carbamate activated sequentially in both
      liver and tumor tissues by carboxylesterases, cytidine deaminase, and thymidine
      phosphorylase. 5-Fluorouracil is inactivated by dihydropyrimidine dehydrogenase
      and targets thymidylate synthase. Here we report the validation of the real-time
      polymerase chain reaction assay for the quantification of the transcripts of the
      different enzymes involved in capecitabine activation. The method is specific,
      sensitive, and linear over 2-3 logs of RNA input. It is reproducible with less
      than 5% intraday variability and less than 10% interday variability. Five
      reference genes were tested for normalization. POLR2A was selected since it
      reduced variability between samples, demonstrated levels of expression similar to
      those of the genes of interest, and its expression was not modified by
      capecitabine treatment in samples from preclinical studies. The method was robust
      as the gene expression profiles from six colon cancer cell lines obtained by this
      method were similar to microarray data. Finally, the method was able to detect
      changes in gene expression in xenograft tumors treated with capecitabine. It
      could therefore constitute the method of choice for future correlative studies in
      patients receiving capecitabine.

PMID- 16438930
TI  - Direct interaction between cohesin complex and DNA replication machinery.
AB  - Structural maintenance of chromosome 1 (Smc1) is a multifunctional protein, which
      has been implicated in sister chromatid cohesion, DNA recombination and repair,
      and the activation of cell cycle checkpoints by ionizing radiation, ultraviolet
      light, and other genotoxic agents. In order to identify the proteins that
      interact with Smc1, we conducted the Tandem affinity purification (TAP) technique
      and analyzed the Smc1-interacting proteins via MALDI-TOF mass spectrometry. We
      identified minichromosome maintenance 7 (Mcm7), an essential component of the pre
      replication complex, as a novel Smc1-interacting protein. Co-immunoprecipitation
      revealed an interaction occurring between Smc1 and Mcm7, both in vitro and in
      vivo. Using a GST pull-down assay, we determined that Smc1 interacts physically
      with Mcm7 via its N-terminal and hinge regions, and Mcm7 interacts with Smc1 via
      its middle region. Interestingly, we also discovered that Smc1 interacts with
      other DNA replication proteins, including Mcm6, RFC1, and DNA polymerase alpha.
      These results suggest that a functional link exists between the cohesin complex
      and DNA replication proteins.

PMID- 16438931
TI  - PKA-mediated protein phosphorylation regulates ezrin-WWOX interaction.
AB  - The ezrin-radixin-moesin proteins provide a regulated linkage between membrane
      proteins and the cortical cytoskeleton, and also participate in signal
      transduction pathways. Ezrin is localized to the apical membrane of parietal
      cells and couples the cAMP-dependent protein kinase activation cascade to the
      regulated HCl secretion in gastric parietal cells. Our recent studies have mapped
      the PKA-mediated phosphorylation site to Ser(66) and established its functional
      role in parietal cell activation [R. Zhou et al., Characterization of protein
      kinase A-mediated phosphorylation of ezrin in gastric parietal cell activation,
      J. Biol. Chem. 278 (2003) 35651-35659], but the underlying basis for this
      regulation is not known. Here, we provide the first evidence that PKA-mediated
      phosphorylation of Ser(66)regulates the interaction of ezrin with WWOX, a WW
      domain-containing protein. Our biochemical study reveals that ezrin directly
      binds to the first WW domain of WWOX via its C-terminal tyrosine-containing
      polyproline sequence (470)PPPPPPVY(477). Mutational analyses further demonstrate
      that tyrosine(477) is essential for the ezrin-WWOX interaction. In addition, our
      study shows that PKA-mediated phosphorylation of ezrin is essential and
      sufficient for the apical localization of WWOX protein as disruption of ezrin
      WWOX interaction eliminated the apical localization of WWOX. Finally, our study
      demonstrates the essential role of ezrin-WWOX interaction in the apical membrane
      remodeling associated with H,K-ATPase recruitment. Taken together, these results
      define a novel molecular mechanism underlying phospho-regulation of ezrin
      function by PKA in parietal cell activation.

PMID- 16438932
TI  - Immunosuppressants inhibit hormone-stimulated Mg2+ uptake in mouse distal
      convoluted tubule cells.
AB  - Immunosuppressants such as cyclosporinA and FK506 (tacrolimus) are widely
      prescribed to treat numerous disorders and to treat organ transplant recipients.
      However, cyclosporine A and FK506 are both known to produce hypomagnesaemia. The
      mechanism of this effect is still unclear. The present study determined the
      effects of immunosuppressant treatment on the parathyroid hormone (PTH) mediated
      Mg(2+) uptake and the mitogen-activated protein kinase (MAPK) activation in mouse
      distal convoluted tubule (MDCT) cells. The intracellular Ca(2+) and Mg(2+)
      concentrations in a single MDCT cell were measured by using the fluorescentdye
      Fura-2 AM and Mag-fura-2 AM, respectively. Cyclosporine A and FK506 illicited a
      transient increase of intracellular Ca(2+) from a basal level of 99 +/- 16 nM to
      685 +/- 105 and 608 +/- 96 nM, respectively. In order to determine the Mg(2+)
      transport, the MDCT cells were Mg(2+)-depleted by culturing them in Mg(2+)-free
      media for 16 h, and the Mg(2+) uptake was measured by microfluorescence after
      placing the depleted cells in 1.5mM MgCl(2). The mean rate of Mg(2+) uptake,
      d([Mg(2+)](i))/dt, was 140 +/- 16 nM/s in the control MDCT cells. PTH increased
      the Mg(2+) uptake more than 2 times in this cell. Cyclosporine A (10 microM) and
      FK506 (0.1 microM) did not affect the basal Mg(2+)uptake (140 +/- 16 and 142 +/-
      14 nM/s, respectively), but they inhibited the PTH-stimulated Mg(2+) entry,
      decreasing it from 248+/-12 to 147 +/- 7 and 148 +/- 14 nM/s, respectively. These
      effects were inhibited by L685818, which is a potent competitive antagonist of
      FK506. PTH stimulated the extracellular signal-regulated kinase1/2 (ERK1/2)
      protein synthesis. This PTH-stimulated ERK1/2 activation was inhibited by
      cyclosporine A and FK506. In the present study, the role of ERK1/2 activation on
      the PTH-dependent magnesium uptake was examined in MDCT cells, and we showed that
      immunosuppressants inhibit the hormone-stimulated Mg(2+) uptake into the MDCT
      cells by inhibiting the MAPK pathway.

PMID- 16438933
TI  - Structural basis of the cofactor function of denatured albumin in plasminogen
      activation by tissue-type plasminogen activator.
AB  - Certain denatured proteins function as cofactors in the activation of plasminogen
      by tissue-type plasminogen activator. The present study approached the structural
      requirements for the cofactor activity of a model protein (human serum albumin).
      Heat denaturation of 100-230 microM albumin (80 degrees C and 60-90 min)
      reproducibly yielded aggregates with radius in the range of 10-150 nm. The major
      determinant of the cofactor potency was the size of the aggregates. The increase
      of particle size correlated with the cofactor activity, and there was a minimal
      requirement for the size of the cofactor (about 10 nm radius). Similar to other
      proteins, the molecular aggregates with cofactor function contained a significant
      amount of antiparallel intermolecular beta-sheets. Plasmin pre-digestion
      increased the cofactor efficiency (related to C-terminal lysine exposure) and did
      not affect profoundly the structure of the aggregates, suggesting a long-lasting
      and even a self-augmenting cofactor function of the denatured protein.

PMID- 16438934
TI  - Human endothelial progenitors constitute targets for environmental atherogenic
      polycyclic aromatic hydrocarbons.
AB  - Cigarette smoking, a well-known cardiovascular risk factor, has been recently
      demonstrated to decrease circulating endothelial progenitor cell (EPC) number.
      Owing to the fact that polycyclic aromatic hydrocarbons (PAHs) such as
      benzo(a)pyrene (BP) constitute major components of tobacco smoke, the present
      study was designed to analyze the effects of these chemicals on the development
      of human EPC cultures from peripheral blood mononuclear cells. Treatment by BP
      markedly impaired EPC number and EPC colonies in a dose-dependent manner. Such
      deleterious effects were abrogated using 3'-methoxy-4'-nitroflavone, a pure
      antagonist of the aryl hydrocarbon receptor, highlighting the involvement of this
      receptor in PAH toxicity towards EPCs. Additional events such as cytochrome P-450
      dependent PAH metabolism and formation of PAH-related adducts to cellular
      macromolecules were also required. Overall, these data established EPCs as new
      cellular targets of PAHs, which may contribute to the deleterious cardiovascular
      effects of environmental substances containing these chemicals, especially
      tobacco smoke.

PMID- 16438935
TI  - Mutation D104G in ANT1 gene: complementation study in Saccharomyces cerevisiae as
      a model system.
AB  - Mutations in the human ANT1 gene, coding for the ADP/ATP carrier, are responsible
      for the autosomal dominant and recessive forms of progressive external
      ophthalmoplegia, mitochondrial disorders characterized by the presence of
      multiple deletions of mitochondrial DNA in affected tissues. By introducing these
      mutations at equivalent position in AAC2, the yeast orthologue of ANT1, we
      created a suitable model for validation of the pathogenicity of the human
      mutations. Here, we describe the use of this approach in the case of mutations
      mapping in domains not conserved between human and yeast, taking advantage of a
      yAAC2/hANT1 chimeric construction as a template to introduce pathogenic hANT1
      mutations. Application to the case of the D104G mutation indicated that the
      chimeric construction could be a tool for validation of pathogenic ANT1 mutations
      in yeast.

PMID- 16438936
TI  - A unified view of the initiation of protein synthesis.
AB  - The mechanism of the initiation of protein synthesis is discussed in terms of two
      different hypotheses in which each emphasized a different possible element of the
      process: the Shine-Dalgarno (SD) hypothesis ascribed an essential role to
      recognition of the SD segment by the ribosomal RNA; it is supported by a variety
      of experiments but conflicting evidence negates its obligatory nature. In
      contrast, our hypothesis highlighted the role of the structure of the mRNA and
      proposes that the initiation codon is selected by virtue of its unique
      accessibility. The rationale for the importance of accessibility in the selection
      of the initiation site is discussed. An analysis and a recapitulation of the
      initiation process and ribosomal specificity are presented. The apparent
      conflicts with the SD hypothesis are resolved in a unified mechanism where
      accessibility is the dominant factor.

PMID- 16438938
TI  - Gelastatins and their hydroxamates as dual functional inhibitors for TNF-alpha
      converting enzyme and matrix metalloproteinases: synthesis, biological
      evaluation, and mechanism studies.
AB  - The hydroxamic acid analogues (2) of the natural product gelastatins (1) were
      prepared by 1 step conversion reaction. The synthetic analogues (2) showed potent
      enzymatic inhibitory activities against MMP-2, MMP-9, and TACE IC50's of 6, 23,
      and 28 nM, respectively. In addition, 2 were able to inhibit TNF-alpha production
      effectively in mice as well as in a macrophage cell line, RAW 264.7. The
      protective effect of 2 also was examined on LPS-induced acute septic shock model.
      The mechanism of TNF-alpha inhibition was examined by RT-PCR and Western blot
      analyses. The relation of TACE and alpha-secretase was examined using cellular
      alpha-secretase assays on IMR-32 and SH-SY5Y cell lines. The docking mode of 2
      with the catalytic domain of TACE was illustrated to analyze the binding mode for
      the further analogue design.

PMID- 16438939
TI  - Searching for a new anti-HCV therapy: synthesis and properties of tropolone
      derivatives.
AB  - Hepatitis C virus (HCV) is considered one of the most dangerous pathogens since
      about 3% of the world population is HCV-infected and the virus is a major cause
      of hepatitis, cirrhosis, and liver carcinoma. A need for a more efficient therapy
      prompted us to investigate new class of compounds, such as tropolone derivatives
      that possess antiviral, antibacterial, and antifungal activities. To synthesize
      bromo- and morpholinomethyl-analogues of tropolone, the previously reported
      methods were modified. The influence of new derivatives on the activity of the
      helicase and NTP-ase of HCV was investigated. The most potent inhibitory effect
      in the fluorometric helicase assay was exerted by 3,7-dibromo-5
      morpholinomethyltropolone, for which the IC50 value was at low micromolar range.
      All the morpholino-derivatives had inhibitory activities higher than those of the
      non-modified analogues. Low toxicity in a yeast-based toxicity assay indicates
      that these compounds could be further modified to develop potent inhibitors of
      the HCV helicase and of viral replication.

PMID- 16438940
TI  - Pyridine N-oxide derivatives inhibit viral transactivation by interfering with NF
      kappaB binding.
AB  - Pyridine N-oxide derivatives represent a new class of anti-HIV compounds for
      which some members exclusively inhibit HIV-1 RT, whereas other members act,
      additionally or alternatively, at a post-integrational event in the replicative
      cycle of HIV. A prototype pyridine N-oxide derivative, JPL-32, inhibited tumor
      necrosis factor alpha (TNF-alpha)-induced HIV-1 expression in latently HIV-1
      infected OM-10.1 and U1 cells, which could be reversed by the addition of N
      acetyl-L-cysteine (NAC). The reversal of the antiviral activity of JPL-32 by NAC
      suggested the possible role of a redox-sensitive factor as target of inhibition.
      Indeed, when nuclear extracts of TNF-alpha-stimulated OM-10.1 and U1 cells
      cultured in the presence of JPL-32 were analyzed by an electrophoretic mobility
      shift assay (EMSA), a dose-dependent inhibition of DNA binding of nuclear NF
      kappaB was observed, which could be reversed by the addition of NAC. JPL-32 did
      not inhibit the release and subsequent degradation of IkappaBalpha, nor did JPL
      32 affect the nuclear translocation of NF-kappaB. EMSA revealed that the
      inhibition of the NF-kappaB DNA binding activity by JPL-32 could be reversed by
      the addition of reducing agents such as dithiothreitol or beta-mercaptoethanol.
      Moreover, JPL-32 was able to directly oxidize the thiol groups on the purified
      p50 subunit of recombinant NF-kappaB. The oxidative modification of the thiol
      groups on NF-kappaB by JPL-32 could be ascribed to the intracellular pro-oxidant
      effect of JPL-32. Consequently, JPL-32 was able to increase the intracellular
      glutathione (GSH) levels and to induce apoptosis in a dose-dependent way.

PMID- 16438942
TI  - Sensory suppression during shifts of attention between surfaces in transparent
      motion.
AB  - During transparent motion, attention to changes in the direction of one illusory
      surface will impede recognition of a similar event affecting the other surface if
      both are close together in time. This is a form of object-based attentional blink
      (AB). Here, we show that this AB is related to a smaller N200 response to the
      change in direction and that the response is even smaller for trials on which the
      subject makes mistakes compared to those with correct responses consistent with
      signal detection theory models. The variation of N200 associated with the AB can
      be modeled by an attenuation of current sources estimated in visual extrastriate
      cortex. These results suggest that the AB in the transparent motion paradigm is
      due to the suppression of sensory signals in early visual areas.

PMID- 16438941
TI  - Sensitization to gimatecan-induced apoptosis by tumor necrosis factor-related
      apoptosis inducing ligand in prostate carcinoma cells.
AB  - Since the intrinsic resistance of prostate carcinoma likely reflects a low
      susceptibility to drug-induced apoptosis, in this study we explored the
      possibility of sensitizing prostate carcinoma cells to apoptosis by combination
      of TRAIL with camptothecins. Indeed, these agents are known to activate different
      pathways of apoptosis. Topotecan- and gimatecan induced moderate up-regulation of
      TRAIL-R1 and -R2 which resulted in a different cell response to the combination
      in androgen-independent cells (DU-145 and PC-3). In DU-145 cells apoptosis was
      increased by lower TRAIL concentrations and was earlier than in PC-3 cells, as
      shown using Annexin V-binding assay. The relative resistance of PC-3 cells to
      drug-induced apoptosis was associated with constitutive Akt activation, higher
      levels of cFLIP-L and Bcl-2, and lower levels of Bax. The different
      expression/activation of apoptosis-related factors appears to influence the
      sensitization of prostate carcinoma cells by TRAIL. Potentiation of camptothecin
      induced apoptosis by TRAIL appears dependent on cooperation between extrinsic and
      intrinsic pathways, as documented by loss of the sensitization to apoptosis
      following reduction of caspase 8 after small interfering RNA transfection. The
      efficacy of the approach may be critically dependent on the intrinsic
      susceptibility to apoptosis of different tumors. These observations support that
      the activation of multiple signals could enhance apoptotic response and suggest
      the therapeutic interest of the TRAIL/camptothecin combination.

PMID- 16438944
TI  - Effects of insulin-like growth factor 1 on voltage-gated ion channels in cultured
      rat hippocampal neurons.
AB  - Insulin-like growth factor 1 (IGF-1) has important functions in the brain,
      including metabolic, neurotrophic, neuromodulatory, and neuroendocrine actions,
      and it is also prevents amyloid beta-induced death of hippocampal neurons.
      However, its functions on the voltage-gated ion channels in hippocampus remain
      uncertain. In the present study, we investigated the effects of IGF-1 on voltage
      gated potassium, sodium, and calcium channels in the cultured rat hippocampal
      neurons using the whole-cell patch clamp recordings. Following incubation with
      different doses of IGF-1 for 24 h, a block of the peak transient A-type K+
      currents amplitude (IC50: 4.425 ng/ml, Hill coefficient: 0.621) was observed. In
      addition, after the application of IGF-1, the amplitude of high-voltage activated
      Ca2+ currents significantly increased but activation kinetics did not
      significantly alter (V1/2: -33.45 +/- 1.32 mV, k = 6.16 +/- 1.05) compared to
      control conditions (V1/2: -33.19 +/- 2.28 mV, k = 7.26 +/- 1.71). However, the
      amplitude of Na+, K+, and low-voltage activated Ca2+ currents was not affected by
      the application of IGF-1. These data suggest that IGF-1 inhibits transient A-type
      K+ currents and enhances high-voltage-activated Ca2+ currents, but has no effects
      on Na+ and low-voltage-activated Ca2+ currents.

PMID- 16438943
TI  - NMDA-receptor proteins are upregulated in the hippocampus of postnatal
      heterozygous reeler mice.
AB  - Reelin is a large glycoprotein that is secreted into the extracellular matrix. In
      the embryonic brain, the binding of Reelin to its receptors ApoER2 and VLDLR
      induces subcellular events that include the activation Fyn tyrosine kinase, and
      plays a crucial role in cortical formation. Reelin signaling is also involved in
      postnatal brain functions such as dendrite development and synaptic plasticity.
      However, the molecular events involved in Reelin signaling in the postnatal brain
      remain to be elucidated. Here, we evaluated the proteins downstream of Reelin
      signaling by comparing the tyrosine-phosphorylated proteins in the postnatal
      hippocampus of heterozygous and homozygous reeler and wild-type mice, by Western
      blot analyses. We found that the levels of several phosphoproteins were highest
      in the hippocampus of the heterozygous reeler mice. The most prominent increase
      was of two 180-kDa phosphoproteins, which were identified as the NR2A and NR2B
      subunits of NMDA-R. The amounts of these proteins also increased in the
      hippocampus of heterozygous reeler mice. However, the mRNA levels of the NMDA-R
      subunits, determined by quantitative RT-PCR, were the same as in wild-type mice.
      We also found that the increase in NR2A and NR2B proteins in heterozygous reeler
      was dependent on Fyn, because this change was absent in heterozygous
      reeler/homozygous Fyn-deficient double-mutant mice. Thus, the NMDA-R protein
      level is regulated by the Reelin protein level in a Fyn-dependent manner in the
      mouse brain.

PMID- 16438945
TI  - Synthesis, structural studies, and cytostatic evaluation of 5,6-di-O-modified L
      ascorbic acid derivatives.
AB  - The 5,6-di-O-tosylated derivative of l-ascorbic acid was synthesized by selective
      protection and deprotection of 2,3- and 5,6-dihydroxy functional groups involving
      5,6-ditosylation in the final step, while the novel 6-acetoxy, 6-hydroxy, and 6
      chloro derivatives of 4,5-didehydro-l-ascorbic acid were obtained by reaction of
      ditosylated compound with nucleophilic reagents. The analysis of 3JH-4-H-5
      homonuclear coupling constants shows that all l-ascorbic acid derivatives except
      for epoxy and 4,5-didehydro compounds exist in high population as gauche
      conformers across C-4-C-5 bonds, while 3JC-3-H-5 heteronuclear coupling constants
      in 4,5-didehydro derivatives indicate cis geometry along C-4-C-5 double bond. The
      X-ray crystal structure analysis of 2,3-di-O-benzyl-5,6-epoxy- and 5,6
      isopropylidene-l-ascorbic acid shows that the oxygen atoms attached at positions
      2 and 3 of the lactone ring are disposed in a synperiplanar fashion. Besides
      that, the dioxolane ring adopts half-chair conformation. The molecules of epoxy
      derivative are joined into infinite chains by one weak hydrogen bond of C-H...O
      type. Two O-H...O, and C-H...O hydrogen bonds link the molecules of 5,6-di-O
      isopropylidene compound into two-dimensional network. 6-Chloro derivative of 2,3
      di-O-benzyl-l-ascorbic acid showed the best cytostatic effects against all tested
      malignant tumor cells (IC50: approximately 18 microM).

PMID- 16438947
TI  - Decision by sampling.
AB  - We present a theory of decision by sampling (DbS) in which, in contrast with
      traditional models, there are no underlying psychoeconomic scales. Instead, we
      assume that an attribute's subjective value is constructed from a series of
      binary, ordinal comparisons to a sample of attribute values drawn from memory and
      is its rank within the sample. We assume that the sample reflects both the
      immediate distribution of attribute values from the current decision's context
      and also the background, real-world distribution of attribute values. DbS
      accounts for concave utility functions; losses looming larger than gains;
      hyperbolic temporal discounting; and the overestimation of small probabilities
      and the underestimation of large probabilities.

PMID- 16438948
TI  - Objective assessment of aesthetic outcomes of breast cancer treatment: measuring
      ptosis from clinical photographs.
AB  - The aesthetic outcome of breast cancer treatment is an important factor in breast
      cancer survivors' quality of life. We investigated new quantitative, objective
      measurements of breast ptosis based on ratios of distances between fiducial
      points manually identified in oblique and lateral clinical photographs. Ptosis
      refers to the extent to which the nipple is lower than the inframammary fold. The
      new objective measures were compared to ratings made using an existing subjective
      scale. The variability in the objective measurements due to intra- and inter
      observer variability in marking fiducial points was shown to be equivalent to
      less than one point on the subjective ptosis scale.

PMID- 16438937
TI  - A catalog for transcripts in the venom gland of the Agkistrodon acutus:
      identification of the toxins potentially involved in coagulopathy.
AB  - Agkistrodon acutus is a special agkistrodon halys, only distributed in Southern
      China, with a few exceptions in Vietnam. It is a cherished element used in
      traditional Chinese medicine. In order to produce a global panorama of gene
      expression in the Agkistrodon acutus venom gland, a non-normalized cDNA library
      was constructed, and 8696 high quality 5' end expressed sequenced tags (ESTs)
      were sequenced and analyzed. The initial sequences were assembled into 2855
      clusters. Of these clusters, only 45.60% clusters matched known sequence and
      54.40% had no match to any known sequence in GenBank. Except for putative
      cellular proteins (1184 clusters), the remaining 118 clusters (40.16% of all
      ESTs) corresponded to sequences associated with diverse toxin function. According
      to expression abundance, the major toxin components were metalloproteinases
      (32.08%) and C-type lectin (5.22%), and other components including bradykinin
      potentiating peptide (0.90%), serine proteases (0.51%), nucleotidase and nuclease
      (0.41%), phospholipase A2 (0.30%), disintegrin (0.05%), cytokine-like molecules
      (0.06%), and other proteins (0.63%). The majority of these components are thought
      to be responsible for coagulopathy after A. acutus bites. We have therefore
      generated a comprehensive catalog of the A. acutus venom gland described so far.
      Gene expression from the very specialized secretory tissue, especially for those
      involved in coagulopathy, can be surveyed and provide important information in
      finding novel toxins.

PMID- 16438946
TI  - Globular adiponectin decreases leptin-induced tumor necrosis factor-alpha
      expression by murine macrophages: involvement of cAMP-PKA and MAPK pathways.
AB  - Several lines of evidence have supported a link between obesity and inflammation.
      The present study investigated the capacity of leptin and globular adiponectin to
      affect tumor necrosis factor alpha (TNF-alpha) production in murine peritoneal
      macrophages. Leptin stimulated TNF-alpha production at mRNA as well as protein
      levels in a dose- and time-dependent manner. Intracellular cAMP concentration was
      increased and protein kinase A (PKA) was activated with the treatment of leptin,
      subsequently downstream MAPK signal proteins, ERK1/2 and p38, were
      phosphorylated. Specific inhibitors for the signal proteins, Rp cAMPS, H89,
      PD98059, and U0126, or SB203580, suppressed the signaling pathway and TNF-alpha
      expression. Although gAd partially increased cAMP concentration and PKA activity,
      it directly reduced leptin-induced ERK1/2 and p38 MAPK phosphorylation thus
      inhibiting TNF-alpha production. In conclusion, leptin promotes inflammation by
      stimulating TNF-alpha production, which is mediated by cAMP-PKA-ERK1/2 and p38
      MAPK pathways. gAd inhibited leptin-induced TNF-alpha production through
      suppressing phosphorylation of ERK1/2 and p38 pathways.

PMID- 16438949
TI  - GABAergic specification in the basal forebrain is controlled by the LIM-hd factor
      Lhx7.
AB  - We present evidence for a temporal control of GABAergic neurotransmitter
      specification in the basal forebrain orchestrated by the LIM-homeodomain factor
      Lhx7. In Xenopus, using in vivo overexpression experiments, we show that x-Lhx7
      and x-Nkx2.1 inhibit GABAergic specification in the Dlx-expressing areas of the
      forebrain (subpallium and diencephalon). In addition, x-Lhx7 almost totally
      represses GABAergic differentiation at early but not late embryonic stages in
      subpallial mouse primary neurons in culture, indicating that x-Lhx7 is not able
      to withdraw the GABAergic phenotype once it is acquired. Moreover, anatomical
      data show striking correlations between x-Lhx7 expression and the
      GABAergic/cholinergic phenotypes. These functional and anatomical observations
      suggest a sequential role for x-Lhx7 in neurotransmitter specification. Thus, x
      Lhx7 would first prevent a pool of cells to become GABAergic early in development
      and then promote cholinergic differentiation later on in this pool. We propose
      two distinct modulatory roles for a single LIM-hd factor, depending on the
      developmental time window.

PMID- 16438950
TI  - Workshop summary: connecting social and environmental factors to measure and
      track environmental health disparities.
AB  - On May 24-25, 2005 in Ann Arbor, Michigan, the US Environmental Protection
      Agency, the National Institute of Environmental Health Sciences, and the
      University of Michigan sponsored a technical workshop on the topic of connecting
      social and environmental factors to measure and track environmental health
      disparities. The workshop was designed to develop a transdisciplinary scientific
      foundation for exploring the conceptual issues, data needs, and policy
      applications associated with social and environmental factors used to measure and
      track racial, ethnic, and class disparities in environmental health. Papers,
      presentations, and discussions focused on the use of multilevel analysis to study
      environmental health disparities, the development of an organizing framework for
      evaluating health disparities, the development of indicators, and the generation
      of community-based participatory approaches for indicator development and use.
      Group exercises were conducted to identify preliminary lists of priority health
      outcomes and potential indicators and to discuss policy implications and next
      steps. Three critical issues that stem from the workshop were: (a) stronger
      funding support is needed for community-based participatory research in
      environmental health disparities, (b) race/ethnicity and socioeconomic position
      need to be included in environmental health surveillance and research, and (c)
      models to elucidate the interrelations between social, physical, and built
      environments should continue to be developed and empirically tested.

PMID- 16438952
TI  - The analgesic activity of paracetamol is prevented by the blockade of cannabinoid
      CB1 receptors.
AB  - The mechanism of the analgesic activity of paracetamol (acetaminophen), one of
      the most widely used drugs for the treatment of pain, is still not clear. Here we
      show that in rats, using the hot plate test, the analgesic effect of paracetamol
      is prevented by two antagonists at cannabinoid CB1 receptors (AM281 and
      SR141716A) at doses that prevent the analgesic activity of the cannabinoid CB1
      agonist HU210. Our present results suggest that paracetamol-induced
      antinociception involves the cannabinoid system.

PMID- 16438951
TI  - The nitric oxide-cyclic GMP-protein kinase G-K+ channel pathway participates in
      the antiallodynic effect of spinal gabapentin.
AB  - The possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G
      (PKG) pathway on gabapentin-induced spinal antiallodynic activity was assessed in
      spinal nerve injured rats. Intrathecal gabapentin, diazoxide or pinacidil reduced
      tactile allodynia in a dose-dependent manner. Pretreatment with NG-L-nitro
      arginine methyl ester (L-NAME, non-specific inhibitor of NO synthase NOS), 7
      nitroindazole (neuronal NO synthase inhibitor), 1H-[1,2,4] -oxadiazolo [4,3-a]
      quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor) or (9S, 10R, 12R)
      2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo
      [1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl
      ester (KT-5823, specific PKG inhibitor), but not NG-D-nitro-arginine methyl ester
      (D-NAME) or okadaic acid (protein phosphatase 1 and 2 inhibitor) prevented
      gabapentin-induced antiallodynia. Pinacidil activity was not blocked by L-NAME, D
      NAME, 7-nitroindazole, ODQ, KT-5823 or okadaic acid. Moreover, KT-5823,
      glibenclamide (ATP-sensitive K+ channel blocker), apamin and charybdotoxin (small
      and large-conductance Ca2+-activated K+ channel blockers, respectively), but not
      margatoxin (voltage-gated K+ channel blocker), L-NAME, 7-nitroindazole, ODQ or
      okadaic acid, reduced diazoxide-induced antiallodynia. Data suggest that
      gabapentin-induced spinal antiallodynia could be due to activation of the NO
      cyclic GMP-PKG-K+ channel pathway.

PMID- 16438953
TI  - S-nitrosocysteine elicits hemodynamic responses similar to those of the Bezold
      Jarisch reflex via activation of stereoselective recognition sites.
AB  - We report here that L-S-nitrosocysteine elicits rapid dose-dependent reductions
      in mean arterial blood pressure, heart rate, cardiac output and renal sympathetic
      nerve activity in conscious rats whereas D-S-nitrosocysteine elicits minor
      responses. The reductions in mean arterial blood pressure, heart rate and cardiac
      output elicited by L- and D-S-nitrosocysteine were markedly diminished after
      blockade of cardiac muscarinic cholinergic receptors whereas the reductions in
      renal sympathetic nerve activity were not affected. The Bezold-Jarisch reflex
      like pattern of responses elicited by the stereoisomers, suggests that (i) L- and
      L-S-nitrosocysteine may activate stereoselective recognition sites on vagal
      cardiopulmonary afferents, which elicit hemodynamic responses via increases in
      cardiovagal efferent nerve activity and decreases in sympathetic nerve activity,
      and (ii) L-S-nitrosocysteine is a more potent agonist of these recognition sites
      than is D-S-nitrosocysteine.

PMID- 16438954
TI  - Different glibenclamide-sensitivity of ATP-sensitive K+ currents using different
      patch-clamp recording methods.
AB  - Electorophysiological and pharmacological properties of the levcromakalim-induced
      inward ATP-sensitive K+ currents (K(ATP) currents) in pig proximal urethra were
      investigated by use of two different whole-cell patch-clamp techniques, namely
      conventional whole-cell and nystatin-perforated patch recordings. In conventional
      whole-cell configuration, the levcromakalim (100 microM)-induced K(ATP) current
      decayed by about 30% in 8 min at a holding potential of -50 mV. In contrast, with
      the nystatin-perforated patch, 96% of the levcromakalim-induced K(ATP) current
      still remained even after 8 min application of levcromakalim. The peak amplitude
      of the levcromakalim-induced inward K(ATP) currents in nystatin-perforated patch
      was approximately half of those observed in conventional whole-cell
      configuration. When cytosolic extract of pig urethra was included in the pipette
      solution, approximately 90% of the levcromakalim (100 microM)-induced K(ATP)
      current remained at 8 min, even after the establishment of conventional whole
      cell configuration. In conventional whole-cell configuration, glibenclamide
      suppressed the levcromakalim-induced K(ATP) currents in a concentration-dependent
      manner (Ki=175 nM). Inclusion of 1 mM uridine 5'-diphosphate (UDP) in the pipette
      solution shifted the glibenclamide-sensitivity (Ki=640 nM) to the right in
      comparison with that in the absence of UDP (i.e., control). In contrast, using
      nystatin-perforated patch, glibenclamide inhibited the levcromakalim-induced
      K(ATP) currents with two affinity sites (high-affinity site, Ki1=10 nM; low
      affinity site, Ki2=9 microM). The concentration response curves regarding the
      inhibitory effects of K(ATP) channel pore blockers (Ba2+ and flecainide) on the
      levcromakalim-induced K(ATP) currents in conventional whole-cell recording nearly
      overlapped with those in nystatin-perforated patch recording. These results
      indicate that the glibenclamide-sensitivity of pig urethral K(ATP) channels in
      nystatin-perforated patch recording was significantly different from that in a
      conventional whole-cell configuration, and that the glibenclamide-sensitivity may
      be modified by some cytosolic factor(s).

PMID- 16438955
TI  - The role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning in
      isolated rat hearts.
AB  - Brief coronary artery occlusion can protect the heart against damage during
      subsequent prolonged coronary artery occlusion; ischemic preconditioning. The
      role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning is
      investigated in isolated perfused rat hearts, by measuring CGRP release during
      ischemic preconditioning and mimicking this by exogenous CGRP infusion, either in
      the absence or presence of the CGRP antagonist BIBN4096BS. CGRP increased left
      ventricular pressure and coronary flow in a concentration dependent manner, which
      was effectively antagonized by BIBN4096BS. Rat hearts (n=36) were subjected to 45
      min coronary artery occlusion and 180 min reperfusion, which was preceded by: (1)
      sham pretreatment, (2) BIBN4096BS infusion (1 microM), (3) preconditioning by 15
      min coronary artery occlusion and10 min reperfusion, (4) as 3, but with
      BIBN4096BS, (5) 15 min CGRP infusion (5 nM) and 10 min washout, (6) as 5, but
      with BIBN4096BS. Cardiac protection was assessed by reactive hyperaemia, creatine
      kinase release, infarct size related to the area at risk (%), and left
      ventricular pressure recovery. Preconditioning increased CGRP release into the
      coronary effluent from 88+/-13 to 154+/-32 pg/min/g, and significantly protected
      the hearts by decreasing reactive hyperaemia (35%), reducing creatine kinase
      release (53%), limiting infarct size (48%), and improving left ventricular
      pressure recovery (36%). Exogenous CGRP induced preconditioning-like
      cardioprotection. BIBN completely abolished the cardioprotection induced by
      preconditioning as well as by exogenous CGRP. In conclusion, since
      cardioprotection of preconditioning-induced CGRP release can be mimicked by
      exogenous CGRP, and both can be blocked by a CGRP antagonist, results indicate an
      important role for CGRP in ischemic preconditioning.

PMID- 16438956
TI  - Pilocarpine improves olfactory discrimination and social recognition memory
      deficits in 24 month-old rats.
AB  - Muscarinic receptor agonists have been suggested as potential drugs to counteract
      age-related cognitive decline since critical changes in cholinergic system occur
      with aging. Recently, we demonstrated that single administration of the non
      selective muscarinic receptor agonist pilocarpine prevents age-related spatial
      learning impairments in rats. In addition, increasing evidence suggests that
      areas in the central nervous system processing olfactory information are affected
      at the early stages of age-related diseases, such as Alzheimer's disease, and
      that specific olfactory testing may represent an important tool in the diagnosis
      of these diseases. In the present study, olfactory discrimination and short-term
      social memory of 3 and 24 month-old rats were assessed with the olfactory
      discrimination and social recognition memory tasks, respectively. The actions of
      the repeated treatment with pilocarpine (30 mg/kg, i.p.; once per day for 21
      days) in relation to age-related effects on olfactory and cognitive functions
      were also studied. The 24 month-old rats exhibited significantly impaired
      performance in both models, demonstrating deficits in their odour discrimination
      and in their ability to recognize a juvenile rat after a short period of time.
      The treatment with pilocarpine improved in a specific manner these age-related
      deficits in 24 month-old rats without altering their motor performance. The
      present results extend the notion of the participation of muscarinic receptors in
      control of olfactory functions and reinforce the potential of muscarinic receptor
      agonists for the treatment of age-related cognitive decline.

PMID- 16438957
TI  - F200A substitution in the third transmembrane helix of human cannabinoid CB1
      receptor converts AM2233 from receptor agonist to inverse agonist.
AB  - To investigate how specific amino acid residues affect human cannabinoid CB1
      receptor binding and activation, CHO cell lines stably expressing wild type and
      the phenylalanine 200 to alanine mutant of human cannabinoid CB1 receptor (F200A)
      were examined. AM2233 functions as an agonist at the wild type receptor
      (EC50=0.93 nM), but behaves as an inverse agonist at F200A (EC50=4.8 nM). The
      F200A mutant has significantly lower forskolin-stimulated basal cAMP accumulation
      than that of the wild type, indicating that the F200A mutant possesses higher
      constitutive activity. F200 doesn't contribute substantially to the high affinity
      binding of AM2233 at human cannabinoid CB1 receptor. CP55940, HU-210 and Win55212
      2 still function as agonists at the F200A mutant, with similar efficacy, potency,
      and apparent binding affinity for both wild type human cannabinoid CB1 receptor
      and F200A mutant. These data indicate that the phenylalanine 200 residue in human
      cannabinoid CB1 receptor is involved in the receptor activation induced by a
      specific class of agonists, and supports a model of agonist-structure-dependent
      conformational changes.

PMID- 16438958
TI  - Pre- and postjunctional effects of angiotensin II in hypertension due to
      adenosine receptor blockade.
AB  - Prejunctional facilitation of [3H]noradrenaline release induced by sympathetic
      nerve stimulation and postjunctional contractile effects of angiotensin II were
      studied in the mesenteric artery and vein of 1,3-dipropyl-8-sulfophenylxanthine
      (DPSPX)-hypertensive rats. Male Wistar rats received infusions of saline or DPSPX
      (90 microg/kg/h) i.p.. Blood pressure was determined by tail-cuff. The
      prejunctional effect of angiotensin II was similar in artery and vein
      preparations of control rats and was increased in DPSPX-hypertensive rats. In
      contrast, the contractile effect of angiotensin II was much more pronounced in
      the mesenteric vein than in the mesenteric artery of control rats and was
      markedly reduced in DPSPX-hypertensive rats. We conclude that (1) the increased
      prejunctional effect of angiotensin II may contribute to, while (2) the decreased
      contractile effect of angiotensin II may attenuate DPSPX-induced hypertension.
      This study also supports the hypothesis that pre- and postjunctional angiotensin
      II receptors are different.

PMID- 16438959
TI  - The nucleotide derivatives inosine and inosinic acid inhibit intestinal
      absorption of mizoribine in rats.
AB  - Inosine is absorbed via a N1 transporter that is selective for purine
      nucleosides. It is conceivable that inosine and inosinic acid might affect the
      intestinal absorption of mizoribine, an imidazole nucleoside that inhibits the de
      novo production pathway of guanine ribonucleotide. An in situ loop experiment was
      performed using four intestinal loop segments prepared by ligation: segment 1,
      about 6 to 9 cm from the end of the pylorus; segment 2, about 10 to 13 cm;
      segment 3, about 14 to 17 cm; and segment 4, about 18 to 21 cm. Mizoribine (0.1
      mg/ml) or mizoribine+inosine (1 or 10 mg/ml) were infused into each loop. The
      absorption rate in the most proximal segment of intestinal loop was the highest.
      In the presence of inosine, this rate decreased significantly. Urinary recovery
      rates of mizoribine were significantly decreased by pretreatment with inosine or
      inosinic acid. The Cmax in the group given mizoribine+inosinic acid was
      significantly lower than that in the group given mizoribine alone. These results
      strongly indicate that (I) the N1 transporter in the intestine might act to
      absorb mizoribine; and (II) inosine and inosinic acid might competitively inhibit
      the absorption of mizoribine via the N1 transporter.

PMID- 16438960
TI  - Dissociation between post-surgical pain behaviors and spinal Fos-like
      immunoreactivity in the rat.
AB  - Previous studies have demonstrated that Fos-like immunoreactivity is increased in
      spinal dorsal horn neurons in several pain models, and have suggested that Fos
      like immunoreactivity could be used as a marker of neurons activated by painful
      stimulation. In the present study, we evaluated nociceptive behaviors and spinal
      Fos-like immunoreactivity in a rat skin incision model of post-operative pain. In
      this model, evoked and non-evoked pain behaviors were observed at least for 2
      days after paw surgery, an increased number of Fos-like immunoreactive neurons
      was observed in the spinal dorsal horn at lumbar levels 4-5 two-hour post
      surgery. The number of Fos-like immunoreactive neurons was significantly greater
      in animals with skin-muscle incision compared to animals with skin-alone
      incision. Interestingly, spinal Fos-like immunoreactivity was quickly normalized
      in rats with paw surgery at later time points (8 and 24 h post-surgery), whereas
      nociceptive behaviors were still observed. Furthermore, at 24 h post-surgery,
      spinal Fos-like immunoreactivity induced by thermal stimulation (42, 44, 46, 48,
      52 degrees C for 15 s) was not significantly different between sham animals and
      animals with surgery. In both groups, an increase in spinal Fos-like
      immunoreactive neurons was observed with increasing temperatures, with similar
      laminar distribution. Finally, systemic morphine reduced post-operative pain and
      Fos-like immunoreactivity in a naloxone reversible manner, with greater potency
      and efficacy on behavioral endpoints than on Fos-like immunoreactivity. These
      results demonstrate a different profile of nociceptive behaviors and spinal Fos
      like immunoreactivity in the rat skin incision model, suggesting a limited
      potential of spinal Fos-like immunoreactivity to study post-surgical pain and its
      pharmacology.

PMID- 16438961
TI  - Neurogenic insulin resistance in guinea-pigs with cisplatin-induced neuropathy.
AB  - The aim of the present work was to study whether neurotoxicity produced by
      cisplatin modified tissue insulin sensitivity in guinea-pigs. One week after
      selective sensory denervation of the anterior hepatic plexus by means of
      perineurial 2% capsaicin treatment, hyperinsulinaemic euglycaemic glucose clamp
      were performed to estimate insulin sensitivity in male guinea-pigs. The guinea
      pigs underwent regional sensory denervation of the anterior hepatic plexus
      exhibited insulin resistance, whereas systemic capsaicin desensitization
      increased insulin sensitivity. Intraportal administration of L-nitro-arginine
      methyl ester (L-NAME decreased, whereas capsaicin increased insulin sensitivity.
      Neither atropine nor acetylcholine produced any significant effect. In animals
      with preceding regional capsaicin desensitization, none of the pharmacological
      maneuvers modified the resulting insulin resistant state. Cisplatin pretreatment
      induced sensory neuropathy and decreased insulin sensitivity. Insulin sensitivity
      did not change after either regional or systemic capsaicin desensitization in the
      cisplatin-treated animals. CGRP(8-37), a nonselective calcitonin gene-related
      peptide (CGRP) antagonist (50 microg/kg i.v.), significantly increased insulin
      sensitivity in normal animals but only a tendency to insulin sensitization was
      seen after cisplatin treatment. Cisplatin treatment, similar to regional
      capsaicin desensitization of the anterior hepatic plexus, produced a significant
      decrease in insulin-stimulated uptake of 2-deoxy-D [L-14C] glucose in cardiac and
      gastrocnemius muscle with no effect on percentage suppression of endogenous
      glucose production by hyperinsulinaemia. We conclude that the majority of
      cisplatin-induced insulin resistance is related to functional deterioration of
      the hepatic insulin sensitizing substance (HISS) mechanism.

PMID- 16438962
TI  - Modulatory effect of interleukin-1beta on rat isolated basilar artery
      contraction.
AB  - An increased level of cytokine interleukin-1 (IL-1) has been detected around the
      site of stroke. However, the effect of IL-1beta on the basilar artery has
      received little attention. We evaluated the effects of IL-1beta on the
      contractile response of rat isolated basilar artery by measuring isometric
      tension change. IL-1beta (10 ng/ml) and phenylephrine (0.1 nM) markedly enhanced
      U46619 (30 and 100 nM)-induced basilar artery contraction. The IL-1beta-mediated
      potentiation was partly suppressed by zinc protoporphyrin (3 microM) and was
      abolished by tetrodotoxin (TTX, 100 nM), (-)-perillic acid (1 microM), PD98059
      (0.3 microM), SB203580 (1 microM) and prazosin (1 microM). Our data suggest that
      IL-1beta (10 ng/ml) causes an enhancement of U46619-mediated basilar artery
      contraction that probably involves TTX-sensitive neuronal release of an alpha1
      adrenoceptor agonist and activation of p42/p44 and p38 mitogen-activated protein
      kinases/p21(ras) pathways.

PMID- 16438963
TI  - Proton pump inhibitors omeprazole and lansoprazole induce relaxation of isolated
      human arteries.
AB  - Vasorelaxant effects of H+/K+-ATPase were previously demonstrated in artery rings
      isolated from experimental animals. We examined the effects of clinically used
      H+/K+-ATPase inhibitors on isolated human internal mammary (n=19) and radial
      (n=5) arteries. Omeprazole and lansoprazole (30-300 microM) both induced
      concentration-dependent, reversible and reproducible relaxations of arteries
      which were precontracted with phenylephrine (5 microM), histamine (15 microM),
      high K+ (80 mM), ouabain (1 microM) and K+ free solution. Relaxant responses were
      similar in both arteries. Presence of Nomega-Nitro-L-arginine methyl ester (30
      microM) had no effect on lansoprazole-induced responses, thus relaxations are
      independent from nitric oxide. Relaxation in the K+ free medium implies that this
      action could not be due to the inhibition of H+/K+-ATPase. Lansoprazole (300
      microM) inhibited Ca2+-induced contractions in high K+-Ca2+ free medium.
      Omeprazole and lansoprazole may act on a common mechanism which plays a crucial
      role in regulating human vascular tone and that mechanism appeared to be involved
      in the regulation of intracellular Ca2+.

PMID- 16438964
TI  - 78 kDa receptor for Man6P-independent lysosomal enzyme targeting: biosynthetic
      transport from endoplasmic reticulum to "high-density vesicles".
AB  - Recent work has shown that the cation-independent mannose 6-phosphate and the 78
      kDa receptors for lysosomal enzyme targeting are located in different cell
      compartments. While the mannose 6-phosphate receptor is enriched in the Percoll
      fractions that contain Golgi apparatus, most of the 78 kDa receptor is localized
      in a heavy fraction at the bottom of the Percoll gradient. This report presents
      the biosynthetic transport of the 78 kDa receptor. Newly synthesized 78 kDa
      receptor was transported to Golgi from endoplasmic reticulum with a half life of
      5 min. From the Golgi apparatus, the receptor takes two routes; about 15-25% is
      transported to the plasma membrane, and the rest migrates to late endosomes,
      subsequently to prelysosomes and finally to the dense vesicles. The 78 kDa
      receptor starts appearing at the dense vesicles 120 min after biosynthesis and
      reaches a maximum of 40-50% of the total receptor. Treatment of cells with NH4Cl
      causes depletion of the receptor from the dense vesicles and prelysosomes and
      corresponding augmentation in endosomes and plasma membrane. These results
      suggest that the 78 kDa receptor cycles between compartments and that the dense
      vesicles seem to represent the most distal compartment in the biosynthetic
      pathway of this receptor.

PMID- 16438965
TI  - Reelin-deficient mice show impaired neurogenesis and increased stroke size.
AB  - Reelin (Reln) is a protein involved in migration of newborn neurons during
      development. Reln mutations produce the reeler phenotype in mice, which is
      characterized by a defect in brain lamination, and autosomal recessive
      lissencephaly in humans. Reln expression persists in adult brain, but little is
      known about its function. We used reeler mice to investigate the effects of Reln
      deficiency on neurogenesis and the response to injury in the adult brain. Newborn
      neurons were decreased in number in the dentate gyrus and rostral migratory
      stream of reeler, compared to wild-type, mice. This was due, at least in part, to
      impaired cell migration. In addition, reeler mice showed increased susceptibility
      to ischemic brain injury. Cerebral infarcts from middle cerebral artery occlusion
      were larger in reeler than in wild-type mice, and associated neurobehavioral
      abnormalities were more severe. The brains of reeler mice also showed larger
      excitotoxic lesions after the intracerebral injection of N-methyl-D-aspartate.
      Finally, despite the fact that reeler mice had larger cerebral infarcts, the
      ischemia-induced enhancement of neurogenesis observed in wild-type mice was
      attenuated. These findings suggest that, in addition to its neurodevelopmental
      effects, Reln deficiency continues to influence neurogenesis and ischemic
      neuronal injury in the adult brain.

PMID- 16438967
TI  - Rediae of echinostomatid and heterophyid trematodes suppress phagocytosis of
      haemocytes in Littorina littorea (Gastropoda: Prosobranchia).
AB  - A modulation of the phagocytic activity of hemocytes from the common periwinkle
      Littorina littorea by secretory-excretory products (SEP) released by trematode
      rediae during axenic in vitro cultivation was studied. The SEP released by the
      parasites Himasthla elongata (Echinostomatidae) and Cryptocotyle lingua
      (Heterophyidae) were found to inhibit the phagocytosis of zymozan particles by
      periwinkle hemocytes. The specificity of SEP effects was assessed: SEP of
      Himasthla militaris and Cryptocotyle concavum, two trematodes belonging to the
      same genera but infecting another closely related prosobranch snail Hydrobia
      ulvae, were also shown to be able to suppress L. littorea hemocytes phagocytic
      activity. However, no decrease in phagocytosis rate was observed when SEP of H.
      elongata and C. lingua were applied to monolayers of hemocytes from the bivalve
      mollusc Mytilus edulis. SEP from H. elongata was fractionated; only those
      fractions containing proteins of molecular weight more than 50 kDa were shown to
      possess inhibitory activity. Different H. elongata SEP concentrations were tested
      in for their ability to suppress phagocytosis by L. littorea hemocytes. Even very
      low SEP concentrations were shown to retain their ability to decrease
      phagocytosis rate, the inhibitory effect being dose-dependent. Hemocytes derived
      from snails naturally infected with H. elongata were also found to have lower
      phagocytic ability as compared to healthy individuals.

PMID- 16438966
TI  - Neurogenin2 identifies a transplantable dopamine neuron precursor in the
      developing ventral mesencephalon.
AB  - In neural transplantation studies, there is an interest in identifying and
      isolating mesencephalic dopamine (mesDA) neuron precursors that have the capacity
      to differentiate into fully mature mesDA neurons after transplantation. We report
      here that in the developing ventral mesencephalon (VM) the proneural gene
      Neurogenin2 (Ngn2) is expressed exclusively in the part of the ventricular zone
      that gives rise to the migrating mesDA neuroblasts, but not in the differentiated
      mesDA neurons. From other studies, we know that Ngn2 is involved in the
      generation of mesDA neurons and that the development of mesDA neurons is severely
      compromised in Ngn2-null mutant mice. We show here that cells isolated by FACS
      from the developing VM of Ngn2-GFP knock-in mice are capable of generating mesDA
      neurons, both in vitro and after transplantation to the striatum of neonatal
      rats. All mesDA neuron precursors, but not the serotonergic or GABAergic neuron
      precursors, are contained in the Ngn2-GFP-expressing population. Moreover, all
      glial cells were generated from cells contained in the GFP-negative cell
      fraction. The results show that surviving mesDA neurons in VM grafts are derived
      from early postmitotic, probably Nurr1-expressing precursors before they have
      acquired their fully differentiated neuronal phenotype. The Ngn2-GFP reporter
      construct used here thus provides a tool for the identification of mesDA neuron
      precursors in the VM and selective isolation of transplantable mesDA neuron
      precursors for transplantation.

PMID- 16438968
TI  - Binding of different monosaccharides by lectin PA-IIL from Pseudomonas
      aeruginosa: thermodynamics data correlated with X-ray structures.
AB  - The lectin from Pseudomonas aeruginosa (PA-IIL) is involved in host recognition
      and biofilm formation. Lectin not only displays an unusually high affinity for
      fucose but also binds to L-fucose, L-galactose and D-arabinose that differ only
      by the group at position 5 of the sugar ring. Isothermal calorimetry experiments
      provided precise determination of affinity for the three methyl-glycosides and
      revealed a large enthalpy contribution. The crystal structures of the complexes
      of PA-IIL with L-galactose and Met-beta-D-arabinoside have been determined and
      compared with the PA-IIL/fucose complex described previously. A combination of
      the structures and thermodynamics provided clues for the role of the hydrophobic
      group in affinity.

PMID- 16438969
TI  - Characterization of human thioredoxin-like-1: potential involvement in the
      cellular response against glucose deprivation.
AB  - The thioredoxin system, composed of thioredoxin (Trx) and thioredoxin reductase
      (TrxR), emerges as one of the most important thiol-based systems involved in the
      maintenance of the cellular redox balance. Thioredoxin-like-1 (TXL-1) is a highly
      conserved protein comprising an N-terminal Trx domain and a C-terminal domain of
      unknown function. Here we show that TXL-1 is a substrate for the cytosolic
      selenoprotein TrxR-1. In situ hybridization experiments demonstrates high
      expression of Txl-1 mRNA in various areas of central nervous system and also in
      some reproductive organs. Glucose deprivation, but not hydrogen peroxide
      treatment, reduced the levels of endogenous TXL-1 protein in HEK-293 cell line.
      Conversely, overexpression of TXL-1 protects against glucose deprivation-induced
      cytotoxicity. Taken together, the finding that Txl-1 mRNA is highly expressed in
      tissues which use glucose as a primary energy source and the modulation of TXL-1
      levels upon glucose deprivation indicate that TXL-1 might be involved in the
      cellular response to sugar starvation stress.

PMID- 16438970
TI  - One of the three proteinase inhibitor genes newly identified in the Brassica
      napus genome codes for an inhibitor of glutamyl endopeptidase.
AB  - Three proteinase inhibitor genes have been identified in the rapeseed (Brassica
      napus) genome. They are highly homologous to other genes of the mustard inhibitor
      (MSI) family of proteinase inhibitors characteristic of Cruciferae. In
      germinating seeds, only the transcript of one gene, coding for a trypsin
      inhibitor, is detectable by Northern analysis. The other two genes are
      transcribed at basal levels detectable only by reverse transcription PCR. One of
      the other two genes (rti-2) encodes a polypeptide with a glutamic residue in the
      P1 position, characteristic of glutamyl proteinase inhibitors. The recombinant
      RTI-2 protein strongly inhibits (Ki=44 nM) a glutamyl proteinase from
      Streptomyces griseus.

PMID- 16438971
TI  - A novel yeast two-hybrid approach to identify CDPK substrates: characterization
      of the interaction between AtCPK11 and AtDi19, a nuclear zinc finger protein.
AB  - Calcium-dependent protein kinases (CDPKs) are sensor-transducer proteins capable
      of decoding calcium signals in diverse phosphorylation-dependent calcium
      signaling networks in plants and some protists. Using a novel yeast two-hybrid
      (YTH) approach with constitutively active and/or catalytically inactive forms of
      AtCPK11 as bait, we identified AtDi19 as an AtCPK11-interacting protein. AtDi19
      is a member of a small family of stress-induced genes. The interaction was
      confirmed using pull-down assays with in vitro translated AtCPK11 and GST-AtDi19
      and localization studies in Arabidopsis protoplasts cotransfected with
      AtCPK11:GFP and AtDi19:DsRed2 protein fusions. We further showed that the
      interaction of AtDi19 is specific to both AtCPK4 and AtCPK11, whereas other
      closely related CPKs from Arabidopsis interacted weakly (e.g., AtCPK12) or did
      not interact (e.g., AtCPK26, AtCPK5 and AtCPK1) with AtDi19. Deletion analyses
      showed that a region containing two predicted nuclear localization signals (NLS)
      and a nuclear export signal (NES) of AtDi19 is essential for interaction with
      AtCPK11. We further demonstrated that AtDi19 is phosphorylated by AtCPK11 in a
      Ca(2+)-dependent manner at Thr105 and Ser107 within the AtDi19 bipartite NLS
      using in vitro kinase assays. Our data suggest that disruption of the
      autoinhibitor domain leading to the formation of a constitutively active CDPK may
      stabilize kinase-substrate interactions without affecting specificity.

PMID- 16438972
TI  - Surgical treatment of displaced fractures of posterior column and posterior wall
      of the of the acetabulum.

PMID- 16438973
TI  - The Web--bringing support and health information into the home: the communicative
      power of qualitative research.

PMID- 16438974
TI  - Cadherin:catenin complex: a novel regulator of vascular smooth muscle cell
      behaviour.
AB  - Dysfunctional vascular smooth muscle cell (VSMC) behaviour contributes to the
      pathogenesis of atherosclerosis and restenosis. Increased rates of VSMC apoptosis
      are thought to lead to thinning of the fibrous atherosclerotic plaque and thereby
      instability, while migration of VSMCs to the intima, and inappropriate VSMC
      proliferation, contribute to intimal thickening that occurs in atherosclerosis
      and restenosis. Studies, mainly in cancer and neuronal cells, have demonstrated
      that cell-cell adhesion by the cadherin:catenin complex modulates apoptosis,
      migration and proliferation. In contrast, until recently the involvement of this
      complex in the regulation of VSMC behaviour was relatively unstudied. In this
      review, evidence for the regulation of VSMC apoptosis, migration and
      proliferation by the cadherin:catenin complex will be discussed.

PMID- 16438976
TI  - Coronary artery calcium, exercise tolerance, and CHD events in asymptomatic men.
AB  - Coronary artery calcium (CAC) scores >/=100 are predictive of CHD events in
      asymptomatic men. Exercise tolerance of >/=10METs predicts lower event rates in
      CHD patients; however, its relationship with events in individuals with
      subclinical atherosclerosis is less known. Participants were 710 asymptomatic men
      from the Aerobics Center Longitudinal Study whose exercise tolerance (ET) was
      quantified (<10 or >/=10METs) and whose CAC score was >/=100 as measured by
      electron beam tomography. During 3.5 years of follow-up 59 CHD events occurred.
      The age-adjusted hazard ratio (HR) of CHD events was 0.26 (95% CI=0.15-0.45) in
      men whose ET was >/=10METs compared with men whose ET was <10METs. Adjustment for
      CHD risk factors and abnormal exercise ECG did not change the association between
      ET and CHD. The extent of underlying atherosclerosis did not influence the
      association between ET and CHD; for example, the HR for CHD events in the
      >/=10MET group among men with CAC scores <400 and >/=400 was 0.16 (95% CI=0.05
      0.56) and 0.23 (95% CI=0.11-0.46), respectively. In asymptomatic men with
      subclinical coronary atherosclerosis, an ET of >/=10METs identifies patients at
      lower risk for manifest CHD.

PMID- 16438975
TI  - Lp-PLA2 activity and PLA2G7 A379V genotype in patients with diabetes mellitus.
AB  - Lipoprotein associated phospholipase A2 (Lp-PLA2) modulates low-density
      lipoprotein (LDL) oxidation by hydrolysing oxidised phospholipids present on
      particle surfaces. We investigated whether Lp-PLA2 activity and PLA2G7 A379V
      genotype were related to mediators of atherosclerosis in a diabetic study. Plasma
      Lp-PLA2 activity (taken in men only) and A379V genotype were investigated with
      regards to metabolic syndrome (MS), UKPDS risk score, and oxidised LDL
      (oxLDL/LDL), in a cohort of Caucasian men and women (n=783, age 62.5+/-13.7
      years). After adjustment for type of diabetes, CHD status, and statin use, those
      individuals with features defining the MS (WHO guidelines) had higher Lp-PLA2
      activity (35.6+/-11.9 nmol/min/ml) compared to those without (33.0+/-10.8
      nmol/min/ml) (p=0.02). Quartiles of UKPDS coronary heart disease (CHD) risk score
      were also positively associated with Lp-PLA2 activity (p=0.006, p=0.004 linear
      trend). Those men in the highest quartile of oxLDL/LDL level had the lowest Lp
      PLA2 activity (31.3+/-10.5 nmol/min/ml) when compared to the middle two (32.3+/
      9.8 and 35.9+/-10.9 nmol/min/ml, respectively) and lowest quartile (35.6 +/-12.5
      nmol/min/ml; p=0.03, p=0.004 linear trend). There was no significant association
      between A379V genotype and Lp-PLA2 enzyme activity (p=0.34) or oxLDL/LDL
      (p=0.32). Lp-PLA2 activity is an independent predictor of CHD risk and MS in a
      sample of subjects with diabetes mellitus. The association of Lp-PLA2 activity
      with oxLDL/LDL suggests that Lp-PLA2 may be a modulating factor in the process of
      atherosclerosis.

PMID- 16438977
TI  - Interleukin-18 levels are not associated with subclinical carotid atherosclerosis
      in a community population. The Perth Carotid Ultrasound Disease Assessment Study
      (CUDAS).
AB  - Interleukin (IL)-18 is a novel proinflammatory cytokine that plays a central role
      in innate and acquired immunity, making it a likely inflammatory candidate in
      atherosclerosis. We investigated whether circulating IL-18 levels were associated
      with subclinical atherosclerosis in a community population. Carotid intimal
      medial thickness (IMT) and carotid plaques were assessed in a cross-sectional
      study of 1111 randomly selected community subjects, aged 27-77 years. Baseline
      levels of IL-18, IL-6, high sensitive CRP (hsCRP), fibrinogen and white cell
      counts were measured along with conventional cardiovascular risk factors. Men had
      higher mean IL-18 levels than women (P<0.0001). Spearman rank correlations (r(s))
      showed that IL-18 was weakly correlated with all inflammatory markers in the
      whole population (r(s) between 0.11 and 0.23, all P<0.001). IL-18 was also
      correlated with conventional risk factors including waist-hip ratio, BMI, blood
      pressure, triglycerides, HDL (inversely) and pack-years smoking (r(s) between
      0.18 and 0.39, all P<0.001) but not with LDL-cholesterol. Independent predictors
      of IL-18 concentrations were waist-hip ratio, HDL, IL-6, hsCRP and hypertension.
      There was a positive univariate association of IL-18 levels with carotid IMT
      (P<0.001) and plaque prevalence (P<0.001) but no residual association after
      adjustment for conventional risk factors (both P>0.05). In a cross-sectional
      community population, IL-18 levels were related to traditional risk factors and
      inflammatory markers but were not independently associated with subclinical
      carotid atherosclerosis.

PMID- 16438978
TI  - The relation between children's conceptual functioning with color and color term
      acquisition.
AB  - Young children experience considerable difficulty in learning their first few
      color terms. One explanation for this difficulty is that initially they lack a
      conceptual representation of color sufficiently abstract to support word meaning.
      This hypothesis, that prior to learning color terms children do not represent
      color as an abstraction, was tested in two experiments using samples of 25- to 39
      month-olds and 20- to 32-month-olds. Children's ability to conceptually represent
      color and their knowledge of color terms were assessed, and a strong association
      was found between the ability to make inferences based on color and the
      comprehension of color words. Children who did not comprehend color terms were
      unsuccessful at a conceptual task that required them to represent color as a
      property independent of the particular objects that displayed it. The results
      suggest that the initial absence of an abstract representation of color
      contributes to the difficulty that young children encounter when first learning
      color words.

PMID- 16438979
TI  - Learning in context: linguistic and attentional constraints on children's color
      term learning.
AB  - Three experiments investigated whether linguistic and/or attentional constraints
      might account for preschoolers' difficulties when learning color terms. Task
      structure and demands were equated across experiments, and both speed and degree
      of learning were compared. In Experiment 1, 3-year-olds who were matched on
      vocabulary score were taught new secondary color terms by corrective, semantic,
      or referential linguistic contrast. Corrective contrast produced more rapid and
      more extensive learning than did either semantic or referential contrast,
      supporting the hypothesis that targeted linguistic feedback facilitates learning.
      Experiment 2 replicated and extended the first experiment with Italian children
      and found cross-cultural differences in the amount learned about colors named
      differently in the two languages. In Experiment 3, some of the children were
      introduced to the new terms within a context of enhanced perceptual salience.
      These children learned as fast and performed as accurately as those given
      corrective linguistic feedback in Experiment 1.

PMID- 16438980
TI  - The effect of question repetition within interviews on young children's
      eyewitness recall.
AB  - This study investigated the influence of question repetition and question type
      (answerable, unanswerable, or opinion seeking) on children's recall. A total of
      136 children (5-, 7-, and 9-year-olds) watched a live 15-min presentation. One
      week later, the children were asked 20 questions that were repeated an additional
      two times within the interview. Accuracy of children's responses to unanswerable
      questions declined with repetition. Children were more likely to change a
      response to an unanswerable question than to an answerable question. Overall,
      children maintained the same answers to only three-quarters of the repeated
      questions. The most common pattern of change was for children to change their
      answer the second time a question was asked and then to maintain that answer when
      questioned again. The high percentage of changed answers within a single
      interview has important implications for forensic interviewing.

PMID- 16438981
TI  - Myocardial homing and neovascularization by human bone marrow angioblasts is
      regulated by IL-8/Gro CXC chemokines.
AB  - In the adult, new blood vessel formation can occur either through angiogenesis
      from pre-existing mature endothelium or vasculogenesis mediated by bone marrow
      derived endothelial precursors. We recently isolated endothelial progenitor
      cells, or angioblasts, in human adult bone marrow which have selective migratory
      properties for ischemic tissues, including myocardium, to where they home and
      induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro
      alpha CXC chemokine family is significantly increased after acute ischemia, and
      that this provides a chemoattractant gradient for bone marrow-derived endothelial
      progenitors, or angioblasts. This chemokine-mediated homing of bone marrow
      angioblasts to the ischemic heart regulates their ability to induce myocardial
      neovascularization, protection against cardiomyocyte apoptosis, and functional
      cardiac recovery. Together, our results indicate that CXC chemokines play a
      central role in regulating vasculogenesis in the adult, and suggest that
      manipulation of interactions between chemokines and their receptors on autologous
      human bone marrow-derived angioblasts could augment neovascularization of
      ischemic myocardial tissue.

PMID- 16438982
TI  - On the mechanism of sequence-specific DNA-dependent acetylation of p53: the
      acetylation motif is exposed upon DNA binding.
AB  - P53 acetylation requires p300-docking to two contiguous sites in the activation
      domain that in turn mediates DNA-dependent acetylation of the tetramer. In an
      attempt to further define the mechanism of DNA-dependent acetylation of p53, an
      in vitro system has been reconstituted with distinct p53 isoforms and has been
      used to reveal conformational constraints on p53 acetylation. Two native p53
      tetrameric isoforms purified from Sf9 cells differing by the extent of
      phosphorylation within the C-terminal acetylation site are both acetylated in a
      sequence-specific DNA-dependent manner. By contrast, p53 purified from an
      Escherichia coli expression system is in a largely denatured conformation and its
      acetylation is DNA-independent. Heating native p53 to destroy the folded
      structure restores DNA-independent acetylation similar to that seen with
      bacterially expressed p53. There are at least two sites of conformational
      flexibility in the p53 tetramer: the first in the flexible S10 beta-sheet within
      the MDM2 ubiquitination sequence and the second in the C-terminal regulatory
      domain. We analysed therefore whether DNA-dependent acetylation correlated with
      conformational changes in either of these two regions. DNA-dependent acetylation
      of p53 is maintained in a dose-dependent manner by low concentrations of
      consensus site DNA under conditions where flexibility in the S10 beta-sheet
      region is maintained. Oligonucleotide DNAs that promote acetylation stimulate the
      binding of monoclonal antibodies PAb421 and ICA-9; two antibodies whose
      contiguous epitopes overlap the C-terminal acetylation motif. By contrast, bent
      oligonucleotide DNAs that conceal both the S10 beta-sheet from binding of the
      monoclonal antibody DO-12 and attenuate binding of the monoclonal antibody PAb421
      can preclude acetylation. These data suggest that, in the absence of DNA, the
      acetylation motif of p53 is in a cryptic state, but after DNA binding, allosteric
      effects mediate an exposure of the acetylation motif to allow DNA-dependent
      acetylation of the tetramer.

PMID- 16438983
TI  - TCP34, a nuclear-encoded response regulator-like TPR protein of higher plant
      chloroplasts.
AB  - We describe the identification of a novel chloroplast protein, designated TCP34
      (tetratricopeptide-containing chloroplast protein of 34 kDa) due to the presence
      of three tandemly arranged tetratricopeptide repeat (TPR) arrays. The presence of
      the genes encoding this protein only in the genomes of higher plants but not in
      photosynthetic cyanobacterial prokaryotes suggests that TCP34 evolved after the
      separation of the higher plant lineage. The in vitro translated precursor could
      be imported into intact spinach chloroplasts and the processed products showed
      stable association with thylakoid membranes. Using a specific polyclonal
      antiserum raised against TCP34, three protein variants were detected. Two forms,
      T(1) and T(2), were associated with the thylakoid membranes and one, S(1), was
      found released in the stroma. TCP34 protein was not present in etioplasts and
      appeared only in developing chloroplasts. The ratio of membrane-bound and soluble
      forms was maximal at the onset of photosynthesis. The high molecular mass
      thylakoid TCP34 variant was found in association with a transcriptionally active
      protein/DNA complex (TAC) from chloroplasts and recombinant TCP34 showed specific
      binding to Spinacia oleracea chloroplast DNA. Two TCP34 forms, T(1) and S(1),
      were found to be phosphorylated. An as yet unidentified phosphorelay signal may
      modulate its capability for plastid DNA binding through the phosphorylation state
      of the putative response regulator-like domain. Based on the structural
      properties and biochemical analyses, we discuss the putative regulatory function
      of TCP34 in plastid gene expression.

PMID- 16438985
TI  - Crystal structure of papaya glutaminyl cyclase, an archetype for plant and
      bacterial glutaminyl cyclases.
AB  - Glutaminyl cyclases (QCs) (EC 2.3.2.5) catalyze the intramolecular cyclization of
      protein N-terminal glutamine residues into pyroglutamic acid with the concomitant
      liberation of ammonia. QCs may be classified in two groups containing,
      respectively, the mammalian enzymes, and the enzymes from plants, bacteria, and
      parasites. The crystal structure of the QC from the latex of Carica papaya (PQC)
      has been determined at 1.7A resolution. The structure was solved by the single
      wavelength anomalous diffraction technique using sulfur and zinc as anomalous
      scatterers. The enzyme folds into a five-bladed beta-propeller, with two
      additional alpha-helices and one beta hairpin. The propeller closure is achieved
      via an original molecular velcro, which links the last two blades into a large
      eight stranded beta-sheet. The zinc ion present in the PQC is bound via an
      octahedral coordination into an elongated cavity located along the pseudo 5-fold
      axis of the beta-propeller fold. This zinc ion presumably plays a structural role
      and may contribute to the exceptional stability of PQC, along with an extended
      hydrophobic packing, the absence of long loops, the three-joint molecular velcro
      and the overall folding itself. Multiple sequence alignments combined with
      structural analyses have allowed us to tentatively locate the active site, which
      is filled in the crystal structure either by a Tris molecule or an acetate ion.
      These analyses are further supported by the experimental evidence that Tris is a
      competitive inhibitor of PQC. The active site is located at the C-terminal
      entrance of the PQC central tunnel. W83, W110, W169, Q24, E69, N155, K225, F22
      and F67 are highly conserved residues in the C-terminal entrance, and their
      putative role in catalysis is discussed. The PQC structure is representative of
      the plants, bacterial and parasite enzymes and contrasts with that of mammalian
      enzymes, that may possibly share a conserved scaffold of the bacterial
      aminopeptidase.

PMID- 16438984
TI  - Co-repressor induced order and biotin repressor dimerization: a case for
      divergent followed by convergent evolution.
AB  - BirA catalyzes the adenylation and subsequent covalent attachment of biotin to
      the biotin carboxyl carrier protein (BCCP). In the absence of apo-BCCP, biotin-5'
      AMP acts as a co-repressor that induces BirA dimerization and binding to the bio
      operator to repress biotin biosynthesis. The crystal structures of apo-BirA, and
      BirA in complex with biotin have been reported. We here describe the 2.8A
      resolution crystal structure of BirA in complex with the co-repressor analog
      biotinol-5'-AMP. It was previously shown that the structure of apo-BirA is
      monomeric and that binding of biotin weakly induces a dimeric structure in which
      three disordered surface loops become organized to form the dimer interface. The
      structure of the co-repressor complex is also a dimer, clearly related to the
      BirA.biotin structure, but with several significant conformational changes. A
      hitherto disordered "adenylate binding loop" forms a well-defined structure
      covering the co-repressor. The co-repressor buttresses the dimer interface,
      resulting in improved packing and a 12 degrees change in the hinge-bending angle
      along the dimer interface relative to the BirA.biotin structure. This helps
      explain why the binding of the co-repressor is necessary to optimize the binding
      of BirA to the bioO operator. The structure reveals an unexpected use of the
      nucleotide-binding motif GXGXXG in binding adenylate and controlling the
      repressor function. Finally, based on structural analysis we propose that the
      class of adenylating enzymes represented by BirA, lipoate protein ligase and
      class II tRNA synthetases diverged early and were selected based on their ability
      to sequester co-factors or amino acid residues, and adenylation activity arose
      independently through functional convergence.

PMID- 16438987
TI  - Speculations surrounding a spinal reflex.
AB  - A method has been developed for measuring the Ia fibre input/motoneurone output
      relationship for the soleus H-reflex in healthy human volunteers. The shift in
      the relationship during weak toe extension, and in some subjects during weak
      plantar flexion, indicates the imposition of an inhibitory mechanism, presumably
      presynaptic. From these observations, and others previously made on long-loop
      reflexes, it is argued that the inhibitory mechanism may have evolved to suppress
      unwanted information from the periphery, not only during movement but in the
      resting state, and that this development was a necessary accompaniment of
      encephalisation.

PMID- 16438986
TI  - Cerebral vasomotor reactivity in Parkinson's disease, multiple system atrophy and
      pure autonomic failure.
AB  - Parkinson's disease (PD), multiple system atrophy (MSA) and pure autonomic
      failure (PAF) are neurodegenerative disorders frequently associated with
      orthostatic hypotension and syncope, though with different underlying mechanisms.
      Cerebral hemodynamic responses in these three neurodegenerative diseases are
      still incompletely studied and it is possible that they would be differentially
      affected. We measured blood flow velocity (BFV) in the middle cerebral artery
      (MCA) and vertebral artery (VA) in patients with these disorders and investigated
      whether cerebral vasomotor reactivity (VMR) differs in these three disorders.
      Twenty-four patients (9 with PD, 10 with MSA and 5 with PAF) were studied. VMR
      was assessed in the MCA and VA, using transcranial Doppler (TCD) and Diamox test
      (injection of 1 g acetazolamide i.v.) with the patients in a recumbent position.
      The percent difference between BFV before and after acetazolamide injection was
      defined as VMR% and the results were compared by ANOVA. The mean MCA and VA blood
      flow velocities were similar in the three disorders and within normal limits for
      our laboratory. The mean MCA VMR values were 37.5+/-24.0%, 27.9+/-28.0% and
      38.0+/-33.9% in PD, MSA and PAF, respectively. The VA VMR values were 22.9+/
      23.6%, 32.4+/-38.0% and 18.9+/-18.3%, respectively, with no significant
      differences between the groups. We conclude that BFV is normal in PD, MSA and PAF
      and that the VMR, as investigated by TCD and the Diamox test, did not disclose
      differences in cerebral vasomotor responses between these conditions.

PMID- 16438988
TI  - Sustainable ecosystem management using optimal control theory: part 1
      (deterministic systems).
AB  - The concept of sustainability, an abstract one by its nature, has been given a
      mathematical representation through the use of Fisher information as a measure.
      It is used to propose the sustainability hypotheses for dynamical systems, which
      has paved the way to achieve sustainable development through externally enforced
      control schemes. For natural systems, this refers to the task of ecosystem
      management, which is complicated due the lack of clear objectives. This work
      attempts to incorporate the idea of sustainability in ecosystem management. The
      natural regulation of ecosystems suggests two possible control options, top-down
      control and bottom-up control. A comparison of these two control philosophies is
      made on generic food chain models using the objectives derived from the
      sustainability hypotheses. Optimal control theory is used to derive the control
      profiles to handle the complex nature of the models and the objectives. The
      results indicate a strong relationship between the hypotheses and the dynamic
      behavior of the models, supporting the use of Fisher information as a measure. As
      regards to ecosystem management, it has been observed that top-down control is
      more aggressive but can result in instability, while bottom-up control is
      guaranteed to give a stable and improved dynamic response. The results also
      indicate that bottom-up control is a better option to affect shifts in the
      dynamic regimes of a system, which may be required to recover the system from a
      natural disaster like the hurricane Katrina.

PMID- 16438989
TI  - Diazepam effects on carrageenan-induced inflammatory paw edema in rats: role of
      nitric oxide.
AB  - High doses of diazepam (10.0-20.0 mg/kg) were shown to reduce the volume of acute
      inflammatory paw edema in rats as a response to carrageenan administration. This
      effect was attributed to an action of diazepam on the peripheral-type
      benzodiazepine receptor (PBR) present in the adrenal and/or immune/inflammatory
      cells. The present study was undertaken to analyze the involvement of nitric
      oxide (NO) on the effects of diazepam on carrageenan-induced paw edema in rats
      (CIPE) and to look for the presence of PBR and inducible/constitutive NO
      synthases (NOS) on slices taken from the inflamed paws of diazepam-treated rats.
      For that, an acute inhibition of NO biosynthesis was achieved using 50.0 mg/kg No
      mega-nitro-L-arginine (L-NAME), L-arginine (300.0 mg/kg), the true precursor of
      NO, and D-arginine (300.0 mg/kg), its false substrate, were also used. The
      following results were obtained: (1) diazepam (10.0 and 20.0 mg/kg) decreased
      CIPE values in a dose- and time-dependent way; (2) diazepam effects on CIPE were
      increased by L-NAME pretreatment; (3) treatment with L-arginine but not with D
      arginine reverted at least in part the decrements of CIPE values observed after
      diazepam administration; (4) PBR were found in endothelial and inflammatory cells
      that migrated to the inflammatory site at the rat paw; (5) confocal microscopy
      showed the presence of both PBR and NOS in endothelial and inflammatory cells
      taken from inflamed paw tissues of rats treated with diazepam a finding not
      observed in tissues provided from rats treated with diazepam's control solution.
      These results suggest an important role for NO on the effects of diazepam on
      CIPE. Most probably, these effects reflect a direct action of diazepam on PBR
      present in the endothelium of the microvascular ambient and/or on
      immune/inflammatory cells. An action like that would lead, among other factors,
      to a decrease in NO, generated by NO synthase, and thus in the mechanisms
      responsible for CIPE.

PMID- 16438990
TI  - Anti-inflammatory action of dietary fish oil and calorie restriction.
AB  - Inflammation, inflammatory mediators, cyclooxygenase (COX)-2, and inducible
      nitric oxide (iNOS) are all influenced by age-related oxidative status. To
      investigate the effect of dietary fish oil (FO) and calorie restriction (CR) on
      oxidative stress-related inflammatory status with age, (NZB/NZW) F1 (B/W) mice
      were fed for 4 and 9 months either ad libitum or calorie-restricted (60% of ad
      libitum intake) diets containing 5% corn oil or 5% FO. We measured several key
      oxidative and inflammatory markers: TBARS, xanthine oxidase (XOD)-derived
      superoxide generation, and PGE2 and LTB4 production. Expressions of renal COX-1,
      COX-2, and iNOS mRNA were analyzed by RT-PCR; additionally, COX-2 protein was
      estimated by Western-blot method. Results show that FO intake and CR individually
      and together suppressed age-related increases in lipid peroxidation and
      superoxide generation. The inhibitory effects of dietary FO and CR were also
      found for iNOS expression, COX-2 expression, which subsequently led to the
      suppression of PGE2 and LTB4. We conclude that the beneficial effects of FO
      feeding and CR are synergistic in ameliorating the age-related nephritis of B/W
      mice by suppressing COX-2 and iNOS, reactive species generation, and pro
      inflammatory mediators.

PMID- 16438991
TI  - Hyperforin: more than an antidepressant bioactive compound?
AB  - Hyperforin is a lipophilic compound that is present in great amounts in St.
      John's wort and that has been described as the main responsible for the
      antidepressant effects of this medicinal plant. In the last few years, evidence
      has accumulated pointing to other different effects of hyperforin with potential
      pharmacological interest. They include other neurological effects, effects on
      inflammation, as well as antibacterial, antitumoral and antiangiogenic effects.

PMID- 16438992
TI  - Long-term L-NAME treatment potentiates the blood-brain barrier disruption during
      pentylenetetrazole-induced seizures in rats.
AB  - We investigated whether the severity of blood-brain barrier disruption caused by
      pentylenetetrazole-induced seizures is modified by long-term nitric oxide
      synthase inhibition in rats. Rats were given N-omega-nitro-L-arginine methyl
      ester (L-NAME), a nitric oxide synthase inhibitor, in drinking water for 4 weeks,
      and then treated with pentylenetetrazole to induce seizures. Damage to the blood
      brain barrier was investigated using Evans blue dye extravasation. Serum nitric
      oxide concentration was decreased in L-NAME-treated rats (P<0.01). L-NAME and/or
      pentylenetetrazole treatments elevated systolic blood pressure of animals
      (P<0.01). L-NAME caused an increase in the mortality rate after
      pentylenetetrazole injection leading to the death of animals at about 15 min
      after the onset of the seizure. Pentylenetetrazole-induced seizures in rats
      treated with L-NAME caused a significant increase in Evans blue dye extravasation
      into cerebral cortex, diencephalon and cerebellum, as compared with seizures
      evoked by pentylenetetrazole injection to L-NAME-untreated rats (P<0.01). Data
      presented here suggest that the degree of blood-brain barrier disruption induced
      by seizures is more pronounced in long-term nitric oxide deficiency.

PMID- 16438993
TI  - Effect of an 8-week resistance training program on cutaneous perfusion in type 2
      diabetes.
AB  - A positive association has previously been demonstrated between chronic aerobic
      exercise and prior maximal exercise and enhanced dorsal foot skin perfusion in
      physically active individuals with type 2 diabetes. The current study examined
      whether an 8-week resistance training program would also positively affect
      cutaneous perfusion in type 2 diabetic individuals. Ten individuals with type 2
      diabetes and nine similar nondiabetic controls participated in 8 weeks of
      moderate-intensity resistance training. Prior to training, dorsal foot cutaneous
      perfusion was measured noninvasively by continuous laser Doppler assessment at
      baseline and during localized heating to 44 degrees C. These measurements were
      repeated exactly 48-72 h following 8 weeks of resistance training performed 3
      days per week. Interstitial nitric oxide (NO) levels were measured concurrently
      in the contralateral foot dorsum. Neither subject group experienced significant
      increases in dorsal foot perfusion responsiveness during local heating to 44
      degrees C following moderate resistance training, nor did the training
      significantly enhance baseline skin perfusion. Interstitial NO levels were not
      significantly different under any condition. At baseline, groups differed only on
      fasting serum glucose and overall glycemic control. In conclusion, the
      responsiveness of cutaneous perfusion in response to heating to 44 degrees C is
      not significantly enhanced by 8 weeks of moderate resistance training in diabetic
      individuals or their matched controls, independent of interstitial NO levels.

PMID- 16438994
TI  - Untargeted effects of ionizing radiation: implications for radiation pathology.
AB  - The dogma that genetic alterations are restricted to directly irradiated cells
      has been challenged by observations in which effects of ionizing radiation,
      characteristically associated with the consequences of energy deposition in the
      cell nucleus, arise in non-irradiated cells. These, so called, untargeted effects
      are demonstrated in cells that have received damaging signals produced by
      irradiated cells (radiation-induced bystander effects) or that are the
      descendants of irradiated cells (radiation-induced genomic instability).
      Radiation-induced genomic instability is characterized by a number of delayed
      adverse responses including chromosomal abnormalities, gene mutations and cell
      death. Similar effects, as well as responses that may be regarded as protective,
      have been attributed to bystander mechanisms. Whilst the majority of studies to
      date have used in vitro systems, some adverse non-targeted effects have been
      demonstrated in vivo. However, at least for haemopoietic tissues, radiation
      induced genomic instability in vivo may not necessarily be a reflection of
      genomically unstable cells. Rather the damage may reflect responses to ongoing
      production of damaging signals; i.e. bystander responses, but not in the sense
      used to describe the rapidly induced effects resulting from direct interaction of
      irradiated and non-irradiated cells. The findings are consistent with a delayed
      and long-lived tissue reaction to radiation injury characteristic of an
      inflammatory response with the potential for persisting bystander-mediated
      damage. An important implication of the findings is that contrary to conventional
      radiobiological dogma and interpretation of epidemiologically-based risk
      estimates, ionizing radiation may contribute to malignancy and particularly
      childhood leukaemia by promoting initiated cells rather than being the initiating
      agent. Untargeted mechanisms may also contribute to other pathological
      consequences.

PMID- 16438995
TI  - Isolation and characterization of isoinhibitors of the potato protease inhibitor
      I family from the latex of the rubber trees, Hevea brasiliensis.
AB  - Three isoinhibitors have been isolated to homogeneity from the C-serum of the
      latex of the rubber tree, Hevea brasiliensis clone RRIM 600, and named HPI-1, HPI
      2a and HPI-2b. The three inhibitors share the same amino acid sequence (69
      residues) but the masses of the three forms were determined to be 14,893+/-10,
      7757+/-5, and 7565+/-5, respectively, indicating that post-translational
      modifications of the protein have occurred during latex collection. One adduct
      could be removed by reducing agents, and was determined to be glutathione, while
      the other adduct could not be removed by reducing agents and has not been
      identified. The N-termini of the inhibitor proteins were blocked by an acetylated
      Ala, but the complete amino acid sequence analysis of the deblocked inhibitors by
      Edman degradation of fragments from endopeptidase C digestion and mass
      spectrometry confirmed that the three isoinhibitors were derived from a single
      protein. The amino acid sequence of the protein differed at two positions from
      the sequence deduced from a cDNA reported in GenBank. The gene coding for the
      inhibitor is wound-inducible and is a member of the potato inhibitor I family of
      protease inhibitors. The inhibitor strongly inhibited subtilisin A, weakly
      inhibited trypsin, and did not inhibit chymotrypsin. The amino acid residues at
      the reactive site P(1) and P(1)(') were determined to be Gln45 and Asp46,
      respectively, residues rarely reported at the reactive site in potato inhibitor I
      family members. Comparison of amino acid sequences revealed that the HPI
      isoinhibitors shared from 33% to 55% identity (50-74% similarity) to inhibitors
      of the potato inhibitor I family. The properties of the isoinhibitors suggest
      that they may play a defensive role in the latex against pathogens and/or
      herbivores.

PMID- 16438996
TI  - Poverty status and health equity: evidence from rural Bangladesh.
AB  - Many studies have examined the health inequities between different social groups,
      often measured by individual independent variables, such as education, gender,
      ethnicity, geography, rich, poor, etc. Although inequities are increasingly
      widening, a few studies have looked at the health inequity between different
      poverty groups within the poor. The present study, using equity terms, examined
      the use of health services in two rural areas of Bangladesh. Using a multistage
      sampling method, a total of 80 villages were selected from the Bogra and Dinajpur
      sadar thanas (subdistricts) for the study. A total of 4003 households in these
      villages were visited for data collection on mortality and fertility, while data
      related to use of health services was collected from a subsample of 1032
      households. A poverty index, constructed using three variables (household
      landholding, education level of head of household, and self-rated categorization
      of household's annual food security), categorized the households into three
      groups: extreme poor, moderate poor and non-poor. Overall, the data revealed
      considerable inequities in many study indicators between the poor and the non
      poor. However, inequities of varying degrees were also found between the extreme
      poor and the moderate poor. Lower levels of inequities were found between the
      poor and the non-poor in the use of health services, which were easily accessible
      and free of charge (immunization, vitamin A capsule, etc.). On the whole, the
      extreme poor were less likely to use health services than the moderate poor and
      the non-poor, suggesting the need for a more appropriate programme to address
      their pressing health needs.

PMID- 16438997
TI  - Public-private partnerships for equity of access to care for tuberculosis and
      HIV/AIDS: lessons from Pune, India.
AB  - The private medical sector is an important and rapidly growing source of health
      care in India. Private medical providers (PMP) are a diverse group, known to be
      poorly regulated by government policies and variable in the quality of services
      provided. Studies of their practices have documented inappropriate prescribing as
      well as violation of ethical guidelines on patient care. However, despite the
      critique that inequitable services characterise the private medical sector, PMPs
      remain important and preferred providers of primary care. This paper argues that
      their greater involvement in the public health framework is imperative to
      addressing the goal of health equity. Through a review of two research studies
      conducted in Pune, India, to examine the role of PMPs in tuberculosis (TB) and
      HIV/AIDS care, the themes of equity and access arising in private sector delivery
      of care for TB and HIV/AIDS are explored and the future policy directions for
      involving PMPs in public health programmes are highlighted. The paper concludes
      that public-private partnerships can enhance continuity of care for patients with
      TB and HIV/AIDS and argues that interventions to involve PMPs must be supported
      by appropriate research, along with political commitment and leadership from both
      public and private sectors.

PMID- 16438998
TI  - Use of isotope ratio mass spectrometry to detect doping with oral testosterone
      undecanoate: inter-individual variability of 13C/12C ratio.
AB  - The metabolic effect of multiple oral testosterone undecanoate (TU) doses over 4
      weeks was assessed in seven voluntary men. The protocol was designed to detect
      accumulation of the substance by choosing the appropriate spot urines collections
      time and to study the urinary clearance of the substance after weeks of
      treatment. Urines were analysed by a new GC/C/isotope ratio mass spectrometry
      (IRMS) method to establish the delta(13)C-values of testosterone metabolites
      (androsterone and etiocholanolone) together with an endogenous reference compound
      (16(5alpha)-androsten-3alpha-ol). The significant differences in inter-individual
      metabolism following TU intake was illustrated by large variations in delta(13)C
      values of both T metabolites (maximum Deltadelta(13)C-values = 5.5 per thousand),
      as well as by very stable longitudinal T/E profiles and carbon isotopic ratios in
      the first hours following administration. According to T/E ratios and delta(13)C
      values, the washout period after 80 mg TU intake was less than 48 h for all
      subjects and no accumulation phenomenon was observed upon chronic oral
      administration.

PMID- 16439000
TI  - DNA immunization in combination with effective antiretroviral drug therapy
      controls viral rebound and prevents simian AIDS after treatment is discontinued.
AB  - DNA immunization in conjunction with antiretroviral therapy was evaluated in SIV
      infected rhesus macaques treated with [R]-9-[2-phosphonylmethoxypropyl]adenine
      (PMPA). Macaques were immunized monthly with DNA vaccines expressing either SIV
      gag/tat or SIV gag/tat and 19 CD8+ T cell epitopes during 7 months of therapy.
      Half the animals from each group were additionally immunized before infection.
      Only 60% of the animals (4 controls, 20 vaccinated) responded to PMPA (ART
      responders). All 4 ART responder controls demonstrated viral rebound or CD4
      decline after PMPA was withdrawn. In contrast, 17 of 20 vaccinated ART responders
      contained viral rebound for over 7 months after PMPA was withdrawn. Viral control
      correlated with stable CD4 counts, higher lymphoproliferation and an increase in
      the magnitude and breadth of the CD8+ T cell response. Immunizing before
      infection or with multi-epitopes enhanced these effects. These results
      demonstrate that DNA immunization during antiretroviral therapy may be an
      effective strategy to treat HIV infection.

PMID- 16439001
TI  - Submerged microfiltration membrane coupled with alum coagulation/powdered
      activated carbon adsorption for complete decolorization of reactive dyes.
AB  - Even the presence of very low concentrations of dyes (1mgL(-1)) in the effluent
      is highly visible and is considered aesthetically undesirable. It must be removed
      from wastewater completely. This study systematically evaluates the performance
      of adsorption (three kinds of powdered activated carbons), coagulation
      (AlCl3.6H2O) and membrane (submerged hollow fiber microfiltration) processes
      individually in treating two kinds of reactive dyes (Orange 16 and Black 5) and
      then using a hybrid process with combined coagulation-adsorption-membrane
      treatment system. Adsorption capacity and kinetics of Orange 16 were much higher
      and faster than those of Black 5. The dye removal efficiency by coagulation was
      highly dependent on dye concentration and solution pH. The hybrid process
      performance was far more superior that individual process in removing both kinds
      of dyes. It was evident that the combined coagulation-adsorption-membrane process
      has a great potential application for complete reactive dye removal, production
      of high-quality treated water and allows the reduction in the use of coagulant
      and adsorbent.

PMID- 16439002
TI  - Distribution and loadings of polycyclic aromatic hydrocarbons in the Xijiang
      River in Guangdong, South China.
AB  - The Xijiang River is the major tributary of the Pearl River, South China, and is
      the major source water system for more than 4.5 million of urban population and
      28.7 million of rural population. We initiated a systematic study on detection
      and quantification of organic pollutants in both water and suspended particulate
      matter (SPM) for samples collected in a span of 12 months. Our results showed
      that total concentrations of 15 polycyclic aromatic hydrocarbons (PAHs) varied
      from 21.7 to 138 ng l(-1) in water and from 40.9 to 665 microg kg(-1) in SPM. The
      organic carbon normalized distribution coefficients (K(OC)) computed for the PAHs
      were correlated well with their octanol-water partition coefficient (K(OW)). The
      estimated annual loadings of Ant, BaA, and BghiP and the total PAHs in the
      Xijiang River were 1620, 330, 177 and 19,400 kg, respectively. Further analysis
      of the data showed that combustion may be the major source of PAHs and that
      direct leakage of petroleum products may be insignificant.

PMID- 16439003
TI  - Geographical distribution of polybrominated diphenyl ethers (PBDEs) and
      organochlorines in small cetaceans from Asian waters.
AB  - Polybrominated diphenyl ethers (PBDEs) are one of the flame retardants widely
      used in plastics, textiles, electronic appliances, and electrical household
      appliances. In this study, PBDEs and organochlorine compounds (OCs) were
      determined in the archived samples from the Environmental Specimen Bank for
      Global Monitoring (es-BANK) at Ehime University. The blubber of cetaceans found
      stranded along the coasts of Japan, Hong Kong, the Philippines and India during
      the period from 1990 to 2001 were employed for chemical analysis to understand
      the present status of contamination and the specific accumulation of PBDEs. PBDEs
      were detected in all the cetacean samples analyzed, and concentrations were one
      or two orders of magnitude lower than for PCBs and DDTs. Concentrations of PBDEs
      ranged from a low value of 6.0 ng/g lipid wt. in spinner dolphin (Stenella
      longirostris) from India to a high value of 6000 ng/g lipid wt. in Indo-Pacific
      humpback dolphin (Sousa chinensis) from Hong Kong. No difference in PBDE levels
      between coastal and offshore species from Japan was observed, implying the
      existence of pollution sources in this region other than Japan. Highest
      concentrations of PBDEs were found in animals from Hong Kong, followed by Japan,
      and much lower levels from the Philippines and India, suggesting that developing
      nations may also have pollution sources of PBDEs. Geographical distribution of
      PBDEs in Asian waters was different from PCBs but similar to DDTs.

PMID- 16439004
TI  - PAH content, toxicity and genotoxicity of coastal marine sediments from the
      Rovinj area, Northern Adriatic, Croatia.
AB  - Surface marine sediments collected from 8 sampling sites within the Rovinj
      coastal area, Northern Adriatic, Croatia, were used for determining priority
      pollutant polycyclic aromatic hydrocarbons (PAHs) and toxic/genotoxic potential
      of sediment organic extracts. Total PAH concentrations ranged from 32 microg/kg
      (protected area) to 13.2 mg/kg dry weight (harbor) and showed clear differences
      between pristine, urban industrial and harbor areas. PAHs distribution revealed
      their pyrogenic origin with some biogenic influence in harbor. At all sampling
      sites sediment extracts showed toxic potential that was consistent with the
      sediment type. No correlation between toxicity measured by Microtox assay and
      concentrations of individual or total PAHs was found. Noncytotoxic dose of
      sediment extracts showed no genotoxic potential in bacterial umu-test. DNA damage
      is positively related to total PAHs at 4 sampling sites (S-1, S-2, S-3, S-6), but
      the highest DNA damage was not observed at the site with the highest total
      sediment PAH content (S-5).

PMID- 16439005
TI  - Reclassification of a tubal leiomyosarcoma as an eGIST by molecular evaluation of
      c-KIT.
AB  - BACKGROUND: Extragastrointestinal stromal tumors (eGISTs) are rare mesenchymal
      derived tumors arising outside of the GI tract. eGISTs are often histologically
      confused with leiomyosarcoma. Distinction between eGIST and leiomyosarcoma is
      critical because of the unique responsiveness of eGISTs to the molecularly
      targeted agent imatinib. CASE: A woman presented with a history of tubal spindle
      cell tumor that was initially diagnosed and treated as a leiomyosarcoma. Because
      of minimal response to sarcoma directed chemotherapy, the possibility that the
      tumor was in fact an eGIST was investigated and supported by immunohistochemical
      and mutational analyses of the c-Kit receptor tyrosine kinase. The patient
      currently has stable disease control on imatinib for the last 18 months.
      CONCLUSIONS: The possibility of eGIST should be considered in the differential
      diagnosis of tumors with a spindle cell morphology in the gynecologic tract
      especially when involving the ovary, fallopian tube, or uterine serosa.

PMID- 16439006
TI  - Modafinil-induced modulation of working memory and plasma corticosterone in
      chronically-stressed mice.
AB  - The original aims of our study were to investigate the dose-effect relationship
      of modafinil administration on working memory performance, in parallel with the
      measurement of plasma corticosterone in chronically-stressed mice, as compared to
      control mice. Memory performance was evaluated by spontaneous alternation in a T
      maze. Vehicle or modafinil (8, 16 or 32 mg/kg) were administered after or without
      chronic stress (immobilization and exposure to light) for 15 min/day over a
      period of consecutive 14 days. Immediately after behavioral testing, blood was
      sampled to measure plasma corticosterone levels. Under non-stress conditions,
      corticosterone significantly increased with 16 and 32 mg/kg modafinil
      administration. Interestingly, optimal working memory performance was revealed at
      the 16 mg/kg dose. Moreover, no correlation was evidenced between working memory
      performance and plasma corticosterone level in modafinil-treated animals. Under
      stress conditions, corticosterone level was lowered at 8 mg/kg and remained
      unchanged at 16 and 32 mg/kg modafinil. An optimal working memory performance was
      evidenced at 8 mg/kg, which indicated a decrease in the efficiency threshold of
      modafinil under stress. Furthermore, an inverse correlation emerged between
      working memory performance and corticosterone level. Our study evidenced for the
      first time the interaction between stress and memory, in the emotional modulation
      of working memory performance, as a function of the administered dose of
      modafinil.

PMID- 16439007
TI  - Acute zolpidem administration produces pharmacodynamic and receptor occupancy
      changes at similar doses.
AB  - Zolpidem is chemically unrelated to classical benzodiazepines but has
      demonstrated relatively high affinity binding to the alpha(1) GABA(A) receptor.
      To assess pharmacodynamic and neurochemical effects of zolpidem, open-field
      behavior, pentylenetetrazole-induced seizure threshold and benzodiazepine
      receptor binding in vitro were evaluated in the same animal following a single
      dose of zolpidem. Zolpidem (2, 5 and 10 mg/kg), lorazepam (2 mg/kg) or vehicle
      was administered intraperitoneally in male CD-1 mice. Behavioral activity,
      assessed by three open-field parameters, was decreased following the two highest
      doses of zolpidem (5 and 10 mg/kg), and reached significance at the 10 mg/kg
      dose. Locomotor activity was also decreased significantly by lorazepam as
      expected. Pentylenetetrazole-induced seizure threshold was increased with the
      administration of 2 and 10 mg/kg zolpidem as well as with lorazepam. Apparent
      affinity (K(D)) of [3H]flunitrazepam, a non-selective ligand, for the
      benzodiazepine receptor in cortical membrane preparations was not significantly
      changed, while receptor number (Bmax) was decreased at all doses of zolpidem,
      reaching significance at the 10 mg/kg dose. These results confirm that the
      behavioral effects of zolpidem are similar to those of classical benzodiazepines.
      In addition, zolpidem had no significant effect on the affinity of the
      benzodiazepine receptor for [3H]flunitrazepam, but did decrease the density of
      receptor binding sites.

PMID- 16439008
TI  - Regular exercise, anxiety, depression and personality: a population-based study.
AB  - OBJECTIVES: To examine whether regular exercise is associated with anxiety,
      depression and personality in a large population-based sample as a function of
      gender and age. METHODS: The sample consisted of adolescent and adult twins and
      their families (N=19,288) who participated in the study on lifestyle and health
      from The Netherlands Twin Registry (1991-2002). Exercise participation, anxiety,
      depression and personality were assessed with self-report questionnaires.
      RESULTS: The overall prevalence of exercise participation (with a minimum of 60
      min weekly at 4 METs (Metabolic Energy Expenditure Index)) in our sample was
      51.4%. Exercise participation strongly declined with age from about 70% in young
      adolescents to 30% in older adults. Among adolescents, males exercised more,
      whereas, among older adults, females exercised more. Exercisers were on average
      less anxious (-0.18 SD), depressed (-0.29 SD) and neurotic (-0.14 SD), more
      extraverted (+0.32 SD) and were higher in dimensions of sensation seeking
      (from+0.25 SD to+0.47 SD) than non-exercisers. These differences were modest in
      size, but very consistent across gender and age. CONCLUSIONS: This study
      corroborates and extends previous findings: regular exercise is cross-sectionally
      associated with lower neuroticism, anxiety and depression and higher extraversion
      and sensation seeking in the population.

PMID- 16439009
TI  - Seasonal variation of the ovarian follicular dynamics and luteal functions of
      sheep in the subtropics.
AB  - This study was undertaken to describe the development of individual follicles and
      corpora lutea (CL) in Ossimi ewe lambs at different seasons of the year in the
      subtropics. Seven ewe lambs underwent daily ultrasonographic examination for 20
      interovulatory periods (IOP) during spring, winter and autumn. Ovarian follicles
      >or=2 mm and corpora lutea were counted and measured. Blood samples were taken
      for progesterone (P(4)) analysis. All ewe lambs included, but one, were cyclic in
      all seasons studied. Three (65%) and two (35%) follicular waves were detected per
      estrous cycle. None of the characteristics of the large follicles was affected by
      season. Follicles >or=2 mm in diameter were significantly higher in winter. The
      CL developed slowly in autumn. Serum P(4) level was higher in autumn. Double
      ovulation was observed only in autumn. The data demonstrated that Ossimi sheep in
      the subtropics were cyclic in most seasons of the year. Season affected mainly
      the luteal functions with little influences on the follicular characteristics.

PMID- 16439011
TI  - Differences in the response of a striped dolphin (Stenella coeruleoalba) and a
      harbour porpoise (Phocoena phocoena) to an acoustic alarm.
AB  - Small cetacean bycatch in gillnet fisheries may be reduced by deterring
      odontocetes from nets acoustically. However, different odontocete species may
      respond differently to acoustic signals from alarms. Therefore, in this study a
      striped dolphin and a harbour porpoise were subjected simultaneously to sounds
      produced by the XP-10 experimental acoustic alarm. The alarm produced 0.3s tonal
      signals randomly selected from a set of 16 with fundamental frequencies between 9
      and 15kHz, with a constant pulse interval of 4.0s (duty cycle 8%) and a Source
      Level range of 133-163dB re 1muPa (rms). The effect of the alarm was judged by
      comparing the animals' respiration rate and position relative to the alarm during
      test periods with those during baseline periods. As in a previous study on two
      porpoises with the same alarm, the porpoise in the present study reacted strongly
      to the alarm by swimming away from it and increasing his respiration rate. The
      striped dolphin, however, showed no reaction to the active alarm. Based on
      harbour porpoise audiograms and the specific audiogram of the striped dolphin in
      the present study, and the low background noise levels during the experiment,
      both animals must have heard the alarm signals clearly. This study indicates that
      cetacean species are not equally sensitive to human-made noise disturbance.
      Therefore, source levels of acoustic alarms should be adapted to the species they
      are supposed to deter. In addition, alarms should be tested on each odontocete
      species for which they are intended to reduce bycatch.

PMID- 16439010
TI  - Intravaginal insemination of bitches with fresh and frozen-thawed semen with
      addition of prostatic fluid: use of an infusion pipette and the Osiris catheter.
AB  - One hundred fifty-two bitches of seven breeds were vaginally inseminated with
      fresh or frozen-thawed semen of 10 stud dogs of respective breeds. The semen was
      supplemented with prostatic fluid before insemination. In experiment 1 bitches of
      each breed were randomly assigned to three treatment groups, consisting of 29
      females (group 1), 33 females (group 2) and 32 females (group 3). In group 1
      bitches were inseminated into vagina with fresh semen using a bovine infusion
      pipette. In group 2 bitches were inseminated into vagina with fresh semen using
      the Osiris catheter. In group 3 bitches were inseminated with frozen-thawed semen
      with the Osiris catheter. The number of sperms in each insemination dose was
      adjusted to 300 x 10(6). In experiment two bitches were randomly assigned to two
      treatment groups, consisting of 30 females (group A) and 28 females (group B). In
      group A bitches were inseminated with fresh semen, whereas in group B with frozen
      thawed semen. Osiris catheter was used in both groups. The total number of sperms
      was adjusted to provide 250 x 10(6) of progressively motile spermatozoa in each
      insemination dose. In experiment 1 the pregnancy rates/whelping rates were
      86.2/82.8%, 81.8/81.8% and 59.4/59.4% for groups 1, 2 and 3, respectively. The
      differences between group 1 and 3 were statistically significant (p < 0.05). The
      litter sizes at birth/litter sizes at weaning were 5.8+/-2.3/5.4+/-2.0, 6.3+/
      1.4/5.7+/-1.0 and 3.9+/-1.2/3.5+/-1.5 in groups 1, 2 and 3, respectively. The
      litter size at birth and at weaning was reduced (p < 0.05) when frozen-thawed
      semen was used for insemination (group 3). There were not significant (p > 0.05)
      differences in the litter size between groups 1 and 2. In experiment 2 pregnancy
      rates/whelping rates and litter sizes at birth/litter sizes at weaning were
      86.7/86.7%, 60.7/57.1% (p < 0.05) and 6.1+/-1.6/5.7+/-1.7, 4.0+/-1.4/3.8+/-1.4 (p
      < 0.05) in groups A and B, respectively. This study shows that results of AI with
      a fresh semen using a bovine infusion pipette and the Osiris catheter are
      equivalent. The results of the use of the Osiris catheter for vaginal
      insemination of frozen-thawed dog semen extended with prostatic fluid after
      thawing are not encouraging. The pregnancy rate, whelping rate and litter size
      are reduced when frozen-thawed, prostatic fluid-supplemented semen is vaginally
      deposited using the Osiris catheter.

PMID- 16439012
TI  - Bone marrow cell gene expression and tissue construct assembly using octacalcium
      phosphate microscaffolds.
AB  - Calcium phosphates have been widely used in bone and soft tissue applications and
      are of considerable interest as scaffold materials due to properties of
      osteoconduction, resorbability and in some cases osteoinduction. These materials
      are microcrystalline and as such are processed using sintering, surface coating
      or cement technologies. However calcium phosphates containing HPO(4)(2-) ions
      often have layered crystal structures and can form macrocrystals in an aqueous
      environment at room temperature and pressure. This study aimed to investigate the
      potential of octacalcium phosphate (OCP) crystals for the attachment,
      proliferation and differentiation of bone marrow stromal cells and the potential
      of these cell seeded crystals as 'building blocks' for manufacture of self
      supporting macroscale tissue constructs. An inverse relationship between cell
      number and crystal surface area was found and marrow cells grown on OCP crystals
      expressed osteocalcin and osteopontin mRNA, markers of osteoblastic
      differentiation, even in the absence of inductive media additives. Self
      supporting crystal tissue macroscale constructs could be fabricated by culturing
      cell loaded crystals in moulds of the desired shape. Due to the low packing
      efficiency as a consequence of the high aspect ratio of OCP crystals, this
      microscaffold approach may offer the potential for ex vivo construction of large
      volumes of tissue which forms as a physiologically vascularised tissue.

PMID- 16439013
TI  - Use of thermodynamic parameters for design of double-walled microsphere
      fabrication methods.
AB  - Double-walled microspheres (DWMS), with drug localized to the particle core,
      present a promising route for control of drug release rates, for example, by
      varying the degradation rate or erosion mechanism of the polymer used to form the
      shell or the thickness of the shell. DWMS are often difficult to fabricate,
      however. Thermodynamic descriptions for polymer-polymer immiscibility, drug
      distribution between phases and polymer-solution spreading coefficient provide
      predictions of appropriate solvents and polymer concentrations for efficiently
      producing well-formed DWMS. As an example, thermodynamic parameters for a
      polyphosphoester/poly(D,L-lactide-co-glycolide) (PLG) DWMS system, encapsulating
      piroxicam, have been calculated and the predictions tested experimentally.
      Appropriate choices of solvents and initial polymer concentrations resulted in
      DWMS with the desired polyphosphoester shells and piroxicam located selectively
      in PLG cores.

PMID- 16439014
TI  - Control of cell adhesion on poly(methyl methacrylate).
AB  - Keratoprostheses have been constructed from a wide variety of transparent
      materials, including poly(methyl methacrylate) (PMMA). However, the success of
      keratoprosthesis has been plagued by numerous shortcomings that include the
      weakening of the implant-host interface due to weak cell adhesion and opaque
      fibrous membrane formation over the inner surface of the implant due to
      fibroblast attachment. An effective solution requires a surface modification that
      would selectively allow enhanced cell attachment at the implant-host interface
      and reduced cell attachment over the interior surface of the implant. Here, we
      have developed a novel and simple peptide conjugation scheme to modify PMMA
      surfaces, which allowed for region-specific control of cell adhesion. This method
      uses di-amino-PEG, which can be grafted onto PMMA using hydrolysis or aminolysis
      method. PEG can resist cell adhesion and protein adsorption. The
      functionalization of grafted di-amino-PEG molecules with RGD peptide not only
      restored cell adhesion to the surfaces, but also enhanced cell attachment and
      spreading as compared to untreated PMMA surfaces. Long-term cell migration and
      micropatterning studies clearly indicated that PEG-PMMA surfaces with and without
      RGD conjugation can be used to differentiate cell adhesion and control cell
      attachment spatially on PMMA, which will have potential applications in the
      modification of keratoprostheses.

PMID- 16439015
TI  - Distribution of prodynorphin mRNA and its interaction with the NPY system in the
      mouse brain.
AB  - Using radioactive in situ hybridisation, the distribution of prodynorphin mRNA in
      the brains of C57Bl/6 mice was systemically investigated, and double-labelling in
      situ hybridisation was used to determine the extent to which neuropeptide Y (NPY)
      and prodynorphin mRNAs were co-expressed. Our results demonstrate that
      prodynorphin mRNA expression in the mouse brain is localised at specific
      subregions of the olfactory bulb, cortex, hippocampus, amygdala, basal ganglia,
      thalamus, hypothalamus, mesencephalon and myelencephalon. Among the regions
      displaying the most intense labelling were the olfactory tubercle, lateral septum
      (LS), caudate putamen (Cpu), central amygdaloid nucleus (Ce), paraventricular
      hypothalamic nucleus (PVN), supraoptic nucleus (SO), lateral hypothalamic area
      (LHA), ventromedial hypothalamic nucleus (VMH), lateral reticular nucleus (LRt)
      and solitary tract nucleus (NTS). In the arcuate nucleus of the hypothalamus
      (Arc), double-labelling in situ hybridisation revealed that prodynorphin
      expressing neurons also contained NPY mRNA, with a co-localisation rate of
      approximately 88% in the lateral part of the Arc, and 79% in the dorsal part of
      the Arc, respectively, suggesting potential overlapping functions of these two
      neurotransmitters in feeding type behaviour.

PMID- 16439016
TI  - JS-K, a nitric oxide prodrug, induces cytochrome c release and caspase activation
      in HL-60 myeloid leukemia cells.
AB  - Nitric oxide (NO) induces differentiation and apoptosis in acute myelogenous
      leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4
      ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent
      antileukemic activity. JS-K induces apoptosis in HL-60 cells by a caspase
      dependent mechanism. The purpose of this study was to determine the pathway
      through which JS-K induces apoptosis. We show that JS-K alters mitochondrial
      membrane potential (DeltaPsim) and induces cytochrome c release from mitochondria
      into the cytoplasm. Treatment with JS-K resulted in activation of Caspase (Casp)
      9, Casp 3 and Casp 8. JS-K constitutes a promising lead for a new class of anti
      leukemic agents.

PMID- 16439017
TI  - Challenging successive mosquito generations with a densonucleosis virus yields
      progressive survival improvement but persistent, innocuous infections.
AB  - Research on cultivated shrimp suggests that they have the capability to tolerate
      viral pathogens in a highly specific manner by mechanisms currently unknown. The
      phenomenon is difficult to study in detail because they have a generation time of
      1-2yr and lack continuous cell lines. Thus, we developed a mosquito-densovirus
      model to examine whether similar phenomena occur in insects. Serial challenge of
      five generations with a stock densovirus (AThDNV) resulted in progressive
      survival increases from 15% to 58%. Prevalence of AThDNV infection in surviving
      mosquito larvae (confirmed by PCR, histology, in situ hybridization and
      transmission electron microscopy) was relatively high (e.g. 36% in F2) but they
      grew normally to establish each succeeding generation. At the end of five
      generations, comparison of deduced amino acid sequences from genome fragments
      revealed a significantly higher (p=0.02) estimated prevalence of defective
      targets in the survivor virus population (29.7%+/-10.0 SD) than in the stored
      viral population (3.3%+/-5.8 SD). The results paralleled those reported for
      serially passaged C6/36 mosquito cell cultures infected with a densovirus. There,
      reduced infection rates are ascribed to the production of defective interfering
      particles (DIP). Thus, it is possible that the presence of prior AThDNV
      infections with a high level of DIP contributed to improved survival in our
      challenged F4 mosquito population. If so, it suggests that persistent viral
      infections in arthropods may serve in a specific, adaptive manner to reduce the
      incidence and severity of disease.

PMID- 16439018
TI  - A novel transposon-based method for elimination of large bacterial plasmids.
AB  - Elimination or modification of large plasmids of bacteria is often an essential
      step in functional analysis of these replicons. However, the conventional plasmid
      curing procedures such as ethidium bromide and heat treatment are insufficient in
      many cases. For instance, curing of the large virulence plasmid of Salmonella
      Enteritidis 2,102 has failed when these treatments were applied. To overcome the
      difficulties, a two-step transposon-based curing method has been developed.
      First, a Tn10-based transposable unit carrying a Km(R) marker gene and the joined
      IS30 ends transposes from a replication deficient conjugative plasmid into the
      target replicon. Then, the inducible IS30 transposase, using the highly reactive
      joined IS30 ends, mediates deletions or gives rise to the loss of the target
      plasmid. The efficiency of the method has been monitored by the frequency of
      Km(S) colonies after induction of IS30 transposase, and it was shown that the
      Km(S) phenotype often accompanied the complete loss of the virulence plasmid or
      the formation of deletion derivatives. The procedure has been successfully
      applied also in removing the large virulence plasmid from enterotoxigenic
      Escherichia coli (ETEC O147), suggesting that the transposon-based method can be
      a useful tool for eliminating native plasmids in several bacteria.

PMID- 16439019
TI  - Modular architecture of the conjugative plasmid pSVH1 from Streptomyces
      venezuelae.
AB  - The conjugative rolling circle replication (RCR) type plasmid pSVH1 from the
      chloramphenicol producer Streptomyces venezuelae was characterized by DNA
      sequence analysis and insertion/deletion analysis. Nucleotide sequence of the
      12,652 bp pSVH1 revealed 11 open reading frames with high coding probability for
      which putative functions could be assigned. Beside the replication initiator gene
      rep for RCR, pSVH1 contained only genes involved in conjugative transfer. The
      transfer gene traB encoding the septal DNA translocator TraB is regulated by the
      GntR-type transcriptional regulator TraR. Six spd genes involved in intra
      mycelial plasmid spreading are organized in two operons, consisting of two and
      three translationally coupled genes. Subcloning experiments demonstrated that the
      transfer gene traB represents a kill function and localized the pSVH1 minimal
      replicon consisting of rep and the dso origin to a 2072-bp fragment. Plasmid
      pSVH1 showed a modular architecture. Its replication region resembled that of the
      Streptomyces natalensis plasmid pSNA1, while the transfer and spread regions
      involved in conjugative plasmid transfer were highly similar to the corresponding
      regions of the Streptomyces ghanaensis plasmid pSG5.

PMID- 16439020
TI  - Inclusion of a matrix-attached region in a 7SK pol III vector increases the
      efficiency of shRNA-mediated gene silencing in embryonic carcinoma cells.
AB  - RNA interference is a widely used tool for analysis of gene function in mammalian
      cells. Stable knockdown of specific target genes can be maintained in cell lines
      and live organisms using vector-based delivery of short hairpins (shRNAs) driven
      by RNA polymerase III promoters. Here we describe a vector incorporating the
      human 7SK promoter for shRNA-mediated gene silencing in the P19 embryonic
      carcinoma stem cell line. Our preliminary experiments with the 7SK shRNA
      expression vector indicated that its activity could be hindered by random genomic
      integration. In order to counter this inhibitory mechanism, we inserted a matrix
      attached region sequence to generate an episomal vector system. We compared the
      effects of insertion versus exclusion of the MAR sequence on the shRNA-mediated
      gene-specific silencing of the beta-tubulin III and Cyclophilin A genes. While
      the MAR sequence is not strongly correlated with the episomal status of the
      expression vector, our studies indicate that inclusion of the MAR element
      significantly enhances the stability of shRNA-mediated gene silencing in the P19
      stem cells.

PMID- 16439021
TI  - Evidence that IncG (IncP-6) and IncU plasmids form a single incompatibility
      group.
AB  - The Escherichia coli IncG and IncU plasmid incompatibility groups were assigned
      in 1980 and 1981, respectively. Complete plasmid sequences have recently been
      published for both these groups, and revealed that their replication proteins are
      related. We show that when cloned at high-copy-number, putative iterons from the
      previously identified IncG replicon cause strong incompatibility with IncU
      plasmids. Incompatibility, albeit weaker, was also demonstrated between the two
      replicons at their normal low-copy-number. This suggests that a single
      incompatibility group exists. The only known IncG plasmid, Rms149, can replicate
      in Pseudomonas species where it is designated IncP-6. We recommend that the
      combined group be known as IncU (IncP-6 in Pseudomonas spp.).

PMID- 16439022
TI  - Aquatic risk assessment of alcohol ethoxylates in North America and Europe.
AB  - An environmental risk assessment for alcohol ethoxylates (AE) is presented that
      integrates wastewater treatment plant monitoring, fate, and ecotoxicity research
      with a new application of mixture toxicity theory based on simple similar
      concentration addition of AE homologs in a species-sensitivity distribution (SSD)
      context. AEs are nonionic surfactants composed of a homologous series of
      molecules that range in alkyl chain length from 12 to 18 carbons and ethoxylates
      from 0 to 18 units. Chronic ecotoxicity of AE is summarized for 17 species in 60
      tests and then normalized to monitoring data for AE mixtures. To do so, chronic
      aquatic toxicity was first expressed as EC10 per species (the concentration
      predicted to cause a 10% reduction in an important ecological endpoint).
      Normalization integrated several new quantitative structure-activity
      relationships for algae, daphnids, fish, and mesocosms and provided an
      interpretation of toxicity test data as a function of individual homologs in an
      AE mixture. SSDs were constructed for each homolog and the HC5 (hazardous
      concentration protective of 95% of species based on a small biological effect
      [the chronic EC10]) was predicted. Total mass of AE in monitored effluents from
      29 sites in Europe, Canada, and the United States averaged 6.8, 2.8, and 3.55
      microg/L, respectively. For risk assessment purposes, correction of exposure to
      account for fatty alcohol derived from sources other than AE and for sorbed
      components based on experimental evidence was used to determine AE concentrations
      in undiluted (100%) effluents from North America and Europe. Exposure and effect
      findings were integrated in a toxic unit (TU)-based model that considers the
      measured distribution of individual AE homologs in effluent with their
      corresponding SSDs. Use of environmentally relevant exposure corrections
      (bioavailability and accounting for AE-derived alcohol) resulted in TUs ranging
      from 0.015 to 0.212. Low levels of risk are concluded for AE in the aquatic
      environments of Europe and North America.

PMID- 16439023
TI  - Synthesis and oxidation of carboxylate-bridged diiron(II) complexes with
      substrates tethered to primary alkyl amine ligands.
AB  - The synthesis and crystallographic characterization of a series of diiron(II)
      complexes with sterically hindered terphenyl carboxylate ligands and alkyl amine
      donors are presented. The compounds [Fe(2)(mu-O(2)CAr(Tol))(4)(L)(2)]
      (L=NH(2)(CH(2))(2)SBn (1); NH(2)(CH(2))(3)SMe (2); NH(2)(CH(2))(3)CCH (3)), where
      (-)O(2)CAr(Tol) is 2,6-di(p-tolyl)benzoate, and [Fe(2)(mu
      O(2)CAr(Xyl))(2)(O(2)CAr(Xyl))(2)(L)(2)] (L=NH(2)(CH(2))(3)SMe (4);
      NH(2)(CH(2))(3)CCH (5)), where (-)O(2)CAr(Xyl) is 2,6-di(3,5
      dimethylphenyl)benzoate, were prepared as small molecule mimics of the catalytic
      sites of carboxylate-bridged non-heme diiron enzymes. The compounds with the (
      )O(2)CAr(Tol) carboxylate form tetrabridged structures, but those containing the
      more sterically demanding (-)O(2)CAr(Xyl) ligand have only two bridging ligands.
      The ancillary nitrogen ligands in these carboxylate-rich complexes incorporate
      potential substrates for the reactive metal centers. Their oxygenation chemistry
      was studied by product analysis of the organic fragments following decomposition.
      Compound 1 reacts with dioxygen to afford PhCHO in approximately 30% yield,
      attributed to oxidative dealkylation of the pendant benzyl group. Compound 3
      decomposes to form Fe(II)Fe(III) and Fe(III)Fe(IV) mixed-valence species by
      established bimolecular pathways upon exposure to dioxygen at low temperatures.
      Upon decomposition, the alkyne-substituted amine ligand was recovered
      quantitatively. When the (-)O(2)CAr(Tol) carboxylate was replaced by the (
      )O(2)CAr(Xyl) ligand in 5, different behavior was observed. The six-coordinate
      iron(III) complex with one bidentate and two monodentate carboxylate ligands,
      [Fe(O(2)CAr(Xyl))(3)(NH(2)(CH(2))(3)CCH)(2)] (6), was isolated from the reaction
      mixture following oxidation.

PMID- 16439024
TI  - Hemoglobins dioxygenate nitric oxide with high fidelity.
AB  - Distantly related members of the hemoglobin (Hb) superfamily including red blood
      cell Hb, muscle myoglobin (Mb) and the microbial flavohemoglobin (flavoHb)
      dioxygenate nitric oxide (.NO). The reaction serves important roles in .NO
      metabolism and detoxification throughout the aerobic biosphere. Analysis of the
      stoichiometric product nitrate shows greater than 99% double O-atom incorporation
      from Hb(18)O(2), Mb(18)O(2) and flavoHb(18)O(2) demonstrating a conserved high
      fidelity .NO dioxygenation mechanism. Whereas, reactions of .NO with the
      structurally unrelated Turbo cornutus MbO(2) or free superoxide radical (-O.(2))
      yield sub-stoichiometric nitrate showing low fidelity O-atom incorporation. These
      and other results support a .NO dioxygenation mechanism involving (1) rapid
      reaction of .NO with a Fe(III-)O.(2) intermediate to form Fe(III-)OONO and (2)
      rapid isomerization of the Fe(III-)OONO intermediate to form nitrate. A sub
      microsecond isomerization event is hypothesized in which the O-O bond homolyzes
      to form a protein caged [Fe(IV)O .NO(2)] intermediate and ferryl oxygen attacks
      .NO(2) to form nitrate. Hb functions as a .NO dioxygenase by controlling O(2)
      binding and electrochemistry, guiding .NO diffusion and reaction, and shielding
      highly reactive intermediates from solvent water and biomolecules.

PMID- 16439025
TI  - Sex dimorphism in cardiac pathophysiology: experimental findings, hormonal
      mechanisms, and molecular mechanisms.
AB  - The higher cardiovascular risk in men and post-menopausal women implies a
      protective action of estrogen. A large number of experimental studies have
      provided strong support to this concept. However, the recent clinical trials with
      negative outcomes regarding hormone replacement therapy call for "post hoc"
      reassessment of existing information, models, and research strategies as well as
      a summary of recent findings. Sex steroid hormones, in particular estrogen,
      regulate numerous processes that are related to the development and progression
      of cardiovascular disease through a variety of signaling pathways. Use of
      genetically modified models has resulted in interesting information on diverse
      actions mediated by steroid receptors. By focusing on experimental findings, we
      have reviewed hormonal, cellular, and signaling mechanisms responsible for sex
      dimorphism and actions of hormone replacement therapy and addressed current
      limitations and future directions of experimental research.

PMID- 16439026
TI  - Evaluation of a sensitive detection method for peptide arrays prepared by SPOT
      synthesis.
AB  - The growing range of applications for peptide arrays prepared by SPOT synthesis
      confirms that they are a powerful proteomics technique to study numerous aspects
      of molecular interaction events. The most frequent application for peptide arrays
      prepared by SPOT synthesis is the identification of linear epitopes that are
      recognized by antibodies. In the conventional format using secondary antibodies
      for detection unspecific binding and high background have been observed. This
      leads to difficulties in evaluation of developed membranes. Especially for
      application with combinatorial libraries false positive results are to be
      avoided. To circumvent this issue, we directly labeled compounds of interest with
      biotin and detected binding by incubation with streptavidin-horseradish
      peroxidase via chemiluminescence. Optimization of method conditions led to a very
      sensitive detection technique with no or low number of unspecific spots, which is
      superior to conventional detection with secondary antibodies. As one consequence,
      evaluation of competitive assays got more reliable.

PMID- 16439027
TI  - Breeding and maintenance of an Mecp2-deficient mouse model of Rett syndrome.
AB  - In this report, we present a retrospective assessment of our experiences in
      maintaining a colony of Mecp2-deficient mice, and present conditions that we have
      found to foster breeding success of this mutant mouse strain. Data from our
      colony of mutant Mecp2 mice show that the Mecp2-null allele is under-represented
      in the weaned litter population, that litters born to heterozygous Mecp2-null
      females are consistently smaller in number than wild-type, and that fewer litters
      from heterozygous Mecp2-null females survive to weaning age than wild-type. Our
      results also reveal that overall litter viability is significantly higher in
      heterozygous Mecp2-null females that frequently breed, and that the addition of
      sunflower seeds to the cages of expecting dams improves the overall breeding
      success of these mice. Taken together, these data highlight the breeding
      tendencies for this mutant mouse strain, and from these data, we suggest
      strategies to maximise their breeding efficiency.

PMID- 16439028
TI  - Simultaneous bilateral laser Doppler fluxmetry and electrophysiological recording
      during middle cerebral artery occlusion in rats.
AB  - Laser Doppler fluxmetry (LDF) and electrocorticography (ECG) are techniques used
      to indicate successful occlusion of the middle cerebral artery (MCAO) in the
      intraluminal filament model of ischemic stroke. However, each method has several
      advantages and drawbacks. This article describes a simple technique to
      simultaneously and continuously monitor LDF and ECG over both cerebral
      hemispheres. We investigated the potential of this method to improve the
      reliability of the filament model. Thirty male Sprague-Dawley rats were subjected
      to transient MCAO under three different experimental conditions (n=10 each
      group): MCAO in [A] normothermic animals, in [B] animals treated with hypothermia
      and in [C] animals receiving barbiturate for induction of burst suppression.
      Cortical blood flow was continuously recorded bilaterally by LDF and the
      electrocorticogram was continuously recorded over both hemispheres. The results
      show that monitoring of cortical electrophysiological activity by ECG allows
      detection of subarachnoid hemorrhage (SAH) during normal electrophysiological
      status and provides continuous control of barbiturate induced burst suppression
      as well as information about postischemic electrophysiological recovery. ECG did
      not detect MCAO, premature reperfusion, or SAH during burst suppression induced
      by barbiturates. In contrast, MCAO, SAH and premature reperfusion were rapidly
      indicated by LDF. Our findings suggest that simultaneous bilateral LDF and ECG
      during MCAO are of complementary value, in particular if barbiturates are
      investigated.

PMID- 16439029
TI  - Endotoxin preconditioning protects neurones from in vitro ischemia: role of
      endogenous IL-1beta and TNF-alpha.
AB  - We have examined whether changes in the expression of several inflammatory
      factors mediate the neuroprotective action of LPS preconditioning on cerebellar
      granule neurones (CGN) exposed to the mitochondrial toxin 3-nitropropionic acid
      (3-NP), chosen as an in vitro ischemic model. CGN were either directly pre
      treated with LPS or indirectly by exposure to conditioned medium (CM) from LPS
      treated mixed glial cultures obtained from wild type or IL-1beta-knock out mice.
      Following this pre-treatment CGN were incubated with 3-NP and cell viability
      assessed. Our results show that LPS preconditioning in neurones, promotes
      neuronal survival against 3-NP-induced cell death and that endogenous TNF-alpha
      is a critical mediator for the neuroprotective actions of LPS independently of
      the presence of endogenous IL-1beta after 3-NP exposure.

PMID- 16439030
TI  - Primary endoscopic dacryocystorhinostomy in children -- analysis of 18 patients.
AB  - OBJECTIVE: To describe the technique and results of primary endonasal endoscopic
      dacryocystorhinostomy in children with nasolacrimal duct blockage and review of
      literature with comparison of the results in adults. MATERIALS AND METHODS: A
      prospective study was carried out between the months of January 2002 to December
      2004, which included 18 patients. Patients diagnosed as having only nasolacrimal
      duct obstruction were included in this study and an endonasal endoscopic
      procedure was performed. RESULTS: Eighteen children underwent endoscopic the DCR
      procedure. There were 5 males (27.7%) and 13 females (72.3%) with the maximum
      incidence between the age group of 4-7 years (age ranging from 10 months to 11.2
      years). The follow up period ranged from 6 to 19 months average being 8.2 months.
      Relief of symptoms and endoscopic visualization of the patent stoma made into the
      lacrimal sac with sac syringing determined a successful outcome. Seventeen
      patients (94.4%) fulfilled the criteria. CONCLUSION: Our experience suggests that
      endonasal endoscopic DCR without stenting offers the same success rates for
      primary surgery over external DCR as have been established in adults. Moreover,
      it has an added advantage of shorter operative time, less morbidity and avoidance
      of stent related complications.

PMID- 16439031
TI  - 3' gene regulatory elements required for expression of the Plasmodiumfalciparum
      developmental protein, Pfs25.
AB  - Development of sexual stage parasites within the mosquito vector is a crucial
      step in the transmission of Plasmodium parasites. The expression of the P25 and
      P28 proteins on the surface of Plasmodium parasites in the mosquito midgut is
      required for development and hence disease transmission. 3' gene-flanking
      sequences are essential for expression of these critical proteins but the
      nucleotide elements required are poorly defined. Transient gene transfection
      experiments using constructs containing deletions of the 3' gene-flanking region
      of the Plasmodium falciparum P25 homologue, pfs25, reveal that elements necessary
      for protein expression are within 315 nucleotides (nt) of the stop codon. A T
      rich region 137-231 nt from the stop codon is required for expression. The
      nonamer AATAAAATG, 360 nt downstream from the stop codon, enhances expression by
      51 percent. Using 3' RACE analysis, multiple polyadenylation sites from
      endogenous and plasmid-derived pfs25 transcripts were identified. Dissimilarities
      between the identified elements and those of metazoans support the hypothesis
      that definition of P25/28 3' gene regulatory processes may eventually permit the
      development of agents which block malaria transmission but are non-toxic to
      humans.

PMID- 16439032
TI  - An ERP study of visual change detection: effects of magnitude of spatial
      frequency changes on the change-related posterior positivity.
AB  - In event-related brain potential (ERP) studies using a visual S1-S2 matching
      task, change stimuli elicit a posterior positivity at around 100-200 ms. In the
      present study, we investigated the effects of magnitude of spatial frequency
      changes on change-related positivity. Each trial consisted of two sequentially
      presented stimuli (S1-S2), where S2 was either (1) the same as S1 (i.e., NO
      change, p=.40), (2) different from S1 in spatial frequency only (SF-change, .40),
      (3) different in orientation only (OR-change, .10), or (4) different in both
      spatial frequency and orientation (BOTH-change, .10). Further, three magnitude
      conditions (Large, Medium, and Small) were used to examine the effect of the
      magnitude of the spatial frequency change. Participant's (N=12) task was to
      respond to S2 with a change in orientation (from vertical to horizontal, or from
      horizontal to vertical) regardless of the spatial frequency of the stimulus.
      Changes in the spatial frequency elicited change-related positivity at a latency
      range of about 120-180 ms, which was followed by a central negativity (N270) and
      a late positive component (LPC). The amplitude of the change-related positivity
      tends to be enhanced as the magnitude of the change is increased. These results
      support the notion that the change-related positivity reflects memory-based
      change detection in the human visual system.

PMID- 16439033
TI  - Basic emotions are associated with distinct patterns of cardiorespiratory
      activity.
AB  - The existence of specific somatic states associated with different emotions
      remains controversial. In this study, we investigated the profile of
      cardiorespiratory activity during the experience of fear, anger, sadness and
      happiness. ECG and respiratory activity was recorded in 43 healthy volunteers
      during the recall and experiential reliving of one or two potent emotional
      autobiographical episodes and a neutral episode. Univariate statistics indicated
      that the four emotions differed from each other and from the neutral control
      condition on several linear and spectral indices of cardiorespiratory activity.
      Dependent variables were further reduced to five physiologically meaningful
      factors using an exploratory principal component analysis (PCA). Multivariate
      analyses of variance and effect size estimates calculated on those factors
      confirmed the differences between the four emotion conditions. A stepwise
      discriminant analyses predicting emotions using the PCA factors led to a
      classification rate of 65.3% for the four emotions (chance=25%; p=0.001) and of
      72.0-83.3% for pair-wise discrimination (chance=50%; p's<0.05). These findings
      may be considered preliminary in view of the small sample on which the
      multivariate approach has been applied. However, this study emphasizes the need
      to better characterize the multidimensional factors involved in cardio
      respiratory regulation during emotion. These results are consistent with the
      notion that distinct patterns of peripheral physiological activity are associated
      with different emotions.

PMID- 16439034
TI  - A case of slowly progressive type 1 diabetes with unstable glycemic control
      caused by unusual insulin antibody and successfully treated with steroid therapy.
AB  - A 75-year-old man with type 1 diabetes and history of insulin therapy for
      previous 3 years using only human recombinant ones was suffering from unstable
      glycemic control. He had a high level of total insulin and a high titer of
      insulin antibodies (IA) (bound/total ratio: 89.8%). Low affinity constant (k(1):
      0.0312 x 10(8) M(-1)) and high binding capacity (b(1): 51.8 x 10(-8) M) of IA in
      the patient detected by the Scatchard analysis were not compatible with those of
      IA associated with exogenous insulin injections in the diabetic patients, but
      compatible with those of the insulin autoantibodies found in patients with
      insulin autoimmune syndrome (IAS), although he had DRB1*0405, which may have
      protection against IAS development. The glucose infusion rate during
      hyperinsulinemic euglycemic clamp was 2.84 mg/kg/min, suggesting a high level of
      insulin resistance. Steroid pulse therapy (1000 mg for 3 days) aimed at reducing
      the possible effect of the IA on his insulin resistance and glycemic instability
      successfully decreased IA titer (from 89.8 to 58.3%), lowered its binding
      capacity (51.8-9.8 x 10(-8) M), increased glucose infusion rate (from 2.84 to
      5.55 mg/kg/min) and improved glycemic control (HbA(1c): from 10.0 to 7.4%) with
      reduced blood glucose excursion. In conclusion, the alteration in insulin
      pharmacokinetics induced by IA seemed to be the cause of the brittle diabetes of
      the present case. Steroid treatment might be useful for the improvement of
      glycamic control in such patients with high IA levels and unstable blood glucose.

PMID- 16439035
TI  - The effect of misclassification errors on case mix measurement.
AB  - Case mix systems have been implemented for hospital reimbursement and performance
      measurement across Europe and North America. Case mix categorizes patients into
      discrete groups based on clinical information obtained from patient charts in an
      attempt to identify clinical or cost difference amongst these groups. The
      diagnosis related group (DRG) case mix system is the most common methodology,
      with variants adopted in many countries. External validation studies of coding
      quality have confirmed that widespread variability exists between originally
      recorded diagnoses and re-abstracted clinical information. DRG assignment errors
      in hospitals that share patient level cost data for the purpose of establishing
      cost weights affects cost weight accuracy. The purpose of this study is to
      estimate bias in cost weights due to measurement error of reported clinical
      information. DRG assignment error rates are simulated based on recent clinical re
      abstraction study results. Our simulation study estimates that 47% of cost
      weights representing the least severe cases are over weight by 10%, while 32% of
      cost weights representing the most severe cases are under weight by 10%. Applying
      the simulated weights to a cross-section of hospitals, we find that teaching
      hospitals tend to be under weight. Since inaccurate cost weights challenges the
      ability of case mix systems to accurately reflect patient mix and may lead to
      potential distortions in hospital funding, bias in hospital case mix measurement
      highlights the role clinical data quality plays in hospital funding in countries
      that use DRG-type case mix systems. Quality of clinical information should be
      carefully considered from hospitals that contribute financial data for
      establishing cost weights.

PMID- 16439038
TI  - In search of evidence: a small scale study exploring how student nurses accessed
      information for a health needs assignment.
AB  - To help students develop the knowledge and skills necessary to provide evidence
      based practice in nursing, a health needs analysis assignment is incorporated
      within a pre-registration nursing programme. As student nurses have reported
      difficulties in accessing and utilising some of the information needed for this
      assigned task, the aim of the study was to explore their experiences of
      undertaking this assignment. Using a qualitative methodology data was collected
      from focus groups and categorised under three main themes: the challenge of
      evidence gathering; the nature of the support students needed and understanding
      the importance of evidence for practice. This paper illustrates that although
      accessing and utilising material was demanding and required more guidance, the
      biggest challenge lay in making judgements about it and there was a clear
      indication of the need for further support in developing their critical and
      evaluative skills. The quality of debate within the focus groups also led the
      research team to question whether educationalists are making the most of
      capitalising on the rich learning gained from students sharing their experiences
      of undertaking assignments.

PMID- 16439037
TI  - Psoralen analogues: synthesis, inhibitory activity of growth of human tumor cell
      lines and computational studies.
AB  - Eight psoralens have been evaluated for their ability to inhibit the in vitro
      growth of three human tumor cell lines representing different tumor types, MCF-7
      (breast cancer), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer).
      The synthesis of four new psoralens (benzofurocoumarins) is presented as well as
      the results of the ab initio calculations to find the parameters that relate the
      structure with the antitumor activity. This work provides supplementary
      information that could allow the development of new psoralen analogues with this
      type of biological activity.

PMID- 16439036
TI  - Muscarinic acetylcholine receptors mediate oligodendrocyte progenitor survival
      through Src-like tyrosine kinases and PI3K/Akt pathways.
AB  - The function of muscarinic acetylcholine receptors expressed in oligodendrocytes
      and in myelin has remained largely undetermined. Here we present evidence that
      incubation of oligodendrocyte progenitors, deprived of growth factor, with the
      acetylcholine analog carbachol significantly reduced cell death by apoptosis and
      blocked caspase-3 cleavage. This protective effect was reversed by atropine, a
      muscarinic acetylcholine receptor antagonist, as well as by specific inhibitors
      of intracellular signaling molecules, including phosphatidylinositol 3-kinase
      (Wortmannin and LY294002), Akt (Akt inhibitor III) and Src-like tyrosine kinases
      (PP2), but not by the mitogen-activated protein kinase kinase inhibitor, PD98059.
      Activation of Akt by carbachol was antagonized by atropine and inhibited by
      LY294002 and PP2. The Src-like tyrosine kinase inhibitor, PP2, also reduced
      carbachol stimulation of extracellular signal-regulated kinases 1/2 and cAMP
      response element binding protein in a dose-dependent manner. Furthermore,
      carbachol increased tyrosine-phosphorylation of Fyn, a member of the Src-like
      tyrosine kinases. These results indicate that muscarinic acetylcholine receptors
      play an important role in oligodendrocyte progenitor survival through
      transduction pathways involving activation of Src-like tyrosine kinases and
      phosphatidylinositol 3-kinase/Akt.

PMID- 16439039
TI  - Increases of efficacy as vaccine against Brucella abortus infection in mice by
      simultaneous inoculation with avirulent smooth bvrS/bvrR and rough wbkA mutants.
AB  - The Brucella abortus S19 and RB51 strains are the most widely used live vaccines
      against bovine brucellosis. However, both can induce abortion and milk excretion,
      S19 vaccination interferes in serological tests, and RB51 is less effective. We
      have shown previously that a rough wbkAB. abortus mutant is attenuated and a
      better vaccine than RB51 in BALB/c mice, and that mutants in the two-component
      regulatory system bvrS/bvrR are markedly attenuated while keeping a smooth
      lipopolysaccharide (S-LPS). In this work, we tested whether simultaneous
      inoculation with live bvrS increases wbkA vaccine efficacy in mice. Even at high
      doses, the bvrS mutant was cleared much faster from spleens than the wbkA mutant.
      The splenic persistence of the wbkA mutant increased when inoculated along with
      the bvrS mutant, but also with inactivated bvrS cells or with purified B. abortus
      S-LPS, strongly suggesting that S-LPS in the bvrS mutant played a determinant
      role in the wbkA persistence. When inoculated alone, both mutants protected
      against virulent B. abortus but less than when inoculated simultaneously, and the
      protection afforded by the combination was better than that obtained with B.
      abortus S19. Increased protection was also obtained after simultaneous
      inoculation of the wbkA mutant and inactivated bvrS cells or purified S-LPS,
      showing again the role played by the S-LPS in the bvrS cells. In mice, the bvrS
      wbkA combination induced an antibody response reduced with respect to B. abortus
      S19 vaccination. Thus, the simultaneous use of live bvrS and wbkA B. abortus
      mutants seems a promising approach to overcome the problems of the S19 andRB51
      vaccines.

PMID- 16439040
TI  - Functional results after conservative treatment of fractures of the mandibular
      condyle.
AB  - Since the introduction of osteosynthesis materials for rigid internal fixation
      after anatomical reduction there is an ongoing discussion about the treatment of
      condylar fractures of the mandible. Sixty patient files were analyzed and 28
      patients were seen for re-examination and a x-orthopantomogram was taken.
      Functionality was graded with the Helkimo index at an average of 3.0 years follow
      up. The clinical dysfunction index showed: severe symptoms in 11%, moderate
      symptoms in 39%, mild symptoms in 39% and 11% had no symptoms. Index for occlusal
      state showed: 21% severe occusal disturbances, 61% moderate occlusal disturbances
      and 18% no occlusal disturbances. According to the anamnestic dysfunction index
      89% of the patients were symptom-free. The clinical outcome group showed a
      significant left/right ramus length difference compared with a 20-person control
      group. The re-examined group did not significantly differ from the control group.
      Conservative treatment for condylar fractures was successful in only 46%
      according to the 1999 consensus criteria described by Bos et al.

PMID- 16439041
TI  - Variations in the postoperative management of free tissue transfers to the head
      and neck in the United Kingdom.
AB  - Reliable assessment of the perfusion of free tissue transfers has always been a
      challenge for reconstructive microsurgeons. The complexities of flap
      microcirculation are often difficult to assess despite all the subjective and
      objective examination techniques available today, particularly when the free
      tissue transfer is buried, and not visible for monitoring. We investigated the
      post-operative management of free tissue transfers to the head and neck in the
      United Kingdom. Selected results from our survey show that the majority of units
      performed between two and five free tissue transfers to the head and neck region
      per month (n=60, mean=4.13, range<1-12). Clinical tests were used to monitor the
      flaps post-operatively in all units questioned. Hand held doppler was the most
      commonly used adjunctive technique, being routinely used for post-operative
      monitoring by twenty six units, and available for use in eighteen other units
      with the most common indications for use were, slow capillary refill and pale
      colour. Frequency and location of monitoring post-operatively was highly
      variable. Nurses were responsible for the routine monitoring of flaps in almost
      every unit. Thirty four units (57%) had a written protocol in place governing the
      monitoring of free tissue transfers post-operatively. We note the wide variation
      in practice on a national level, and make certain recommendations.

PMID- 16439042
TI  - Application of a new calibration method for a three-dimensional finite element
      model of a human lumbar annulus fibrosus.
AB  - BACKGROUND: Major deficits of many finite element models of the lumbar spine are
      the oversimplification, assumed constellation of the material properties or the
      insufficiently performed calibration using experimental in vitro data. The aim of
      this study was, to develop a method for calibrating the two-composite structure
      of the annulus fibrosus, the ground substance and collagen fibers. METHODS: For
      that purpose, a three-dimensional, non-linear finite element model of a
      denucleated intervertebral disc with the adjacent vertebral bodies (L4-L5) was
      created. Previously performed in vitro experiments provided experimental data for
      the range of motion in each load direction, needed for calibration. A method was
      developed to determine the individual contribution of the fibers and the ground
      substance for bending moments with four different magnitudes (2.5, 5.0, 7.5 and
      10 Nm). For each bending moment, the stiffness of fibers was varied to
      approximate the Young's modulus of the ground substance in order to fulfil the
      required range of motion obtained from in vitro results within an accuracy of
      99%. RESULTS: Infinite material parameter combinations of collagen fibers and
      ground substance led to the same range of motion, which were different for each
      bending moment. However, there was only one combination, which was valid for all
      applied bending moments; and in all load direction. INTERPRETATION: This
      calibration method was performed on range of motion data; however, the procedure
      could also be applied to other loading scenarios and measurement parameters like
      disc bulge, translation and intradiscal pressure.

PMID- 16439043
TI  - Dichlorvos--a comprehensive review of 11 rodent carcinogenicity studies.
AB  - Dichlorvos (DDVP) has been studied in 11 cancer bioassays. Only two studies, the
      National Toxicology Program (NTP) rat and mouse studies, show any indication of
      carcinogenic effects and these results, an increase in mononuclear cell leukemia
      in the rat and an increase in forestomach tumors in the mouse, appear to be
      related to the corn oil vehicle. The increase in mononuclear cell leukemia was
      confined to the male rat, was not dose-related, did not show an earlier onset
      than the controls, had no effect on survival, was within the range seen in
      historical controls, and was not confirmed in five other rat studies, four of
      which used higher doses. The increase in forestomach tumors in mice in the NTP
      study, in which DDVP was administered by corn oil gavage, was confined to the
      highest dose, occurred against a high background of hyperplasia and forestomach
      tumors in the control mice, and was not confirmed in 10 other studies. Sustained
      irritation from daily gavaging with the corn oil vehicle, in conjunction with
      this high background, likely explains this response in the forestomach, which
      does not exist in humans. These 11 rodent studies provide strong evidence that
      DDVP is not carcinogenic.

PMID- 16439044
TI  - Revised assessment of cancer risk to dichloromethane II. Application of
      probabilistic methods to cancer risk determinations.
AB  - An updated PBPK model of methylene chloride (DCM, dichloromethane)
      carcinogenicity in mice was recently published using Bayesian statistical methods
      (Marino et al., 2006). In this work, this model was applied to humans, as
      recommended by Sweeney et al.(2004). Physiological parameters for input into the
      MCMC analysis were selected from multiple sources reflecting, in each case, the
      source that was considered to represent the most current scientific evidence for
      each parameter. Metabolic data for individual subjects from five human studies
      were combined into a single data set and population values derived using MCSim.
      These population values were used for calibration of the human model. The PBPK
      model using the calibrated metabolic parameters was used to perform a cancer risk
      assessment for DCM, using the same tumor incidence and exposure concentration
      data relied upon in the current IRIS entry. Unit risks, i.e., the risk of cancer
      from exposure to 1 microg/m3 over a lifetime, for DCM were estimated using the
      calibrated human model. The results indicate skewed distributions for liver and
      lung tumor risks, alone or in combination, with a mean unit risk (per microg/m3)
      of 1.05 x 10(-9), considering both liver and lung tumors. Adding the distribution
      of genetic polymorphisms for metabolism to the ultimate carcinogen, the unit
      risks range from 0 (which is expected given that approximately 20% of the US
      population is estimated to be nonconjugators) up to a unit risk of 2.70 x 10(-9)
      at the 95th percentile. The median, or 50th percentile, is 9.33 x 10(-10), which
      is approximately a factor of 500 lower than the current EPA unit risk of 4.7 x
      10(-7) using a previous PBPK model. These values represent the best estimates to
      date for DCM cancer risk because all available human data sets were used, and a
      probabilistic methodology was followed.

PMID- 16439045
TI  - Perceptions of social capital and the built environment and mental health.
AB  - There has been much speculation about a possible association between the social
      and built environment and health, but the empirical evidence is still elusive.
      The social and built environments are best seen as contextual concepts but they
      are usually estimated as an aggregation of individual compositional measures,
      such as perceptions on trust or the desirability to live in an area. If these
      aggregated compositional measures were valid measures, one would expect that they
      would evince correlations at higher levels of data collection (e.g.,
      neighbourhood). The aims of this paper are: (1) to investigate the factor
      structure of a self-administered questionnaire measuring individual perceptions
      of trust, social participation, social cohesion, social control, and the built
      environment; (2) to investigate variation in these factors at higher than the
      individual level (households and postcodes) in order to assess if these
      constructs reflect some contextual effect; and (3) to study the association
      between mental health, as measured by the General Health Questionnaire-12 (GHQ
      12), and these derived factors. A cross-sectional household survey was undertaken
      during May-August 2001 in a district of South Wales with a population of 140,000.
      We found that factor analysis grouped our questions in factors similar to the
      theoretical ones we had previously envisaged. We also found that approximately
      one-third of the variance for neighbourhood quality and 10% for social control
      was explained at postcode (neighbourhood) level after adjusting for individual
      variables, thus suggesting that some of our compositional measures capture
      contextual characteristics of the built and social environment. After adjusting
      for individual variables, trust and social cohesion, two key social capital
      components were the only factors to show statistically significant associations
      with GHQ-12 scores. However, these factors also showed little variation at
      postcode levels, suggesting a stronger individual determination. We conclude that
      our results provide some evidence in support of an association between mental
      health (GHQ-12 scores) and perceptions of social capital, but less support for
      the contextual nature of social capital.

PMID- 16439046
TI  - Flare up rate related to root canal treatment of asymptomatic pulpally necrotic
      central incisor teeth in patients attending a military hospital.
AB  - OBJECTIVES: This prospective study was conducted to determine the flare up rate
      related to root canal treatment of asymptomatic non vital maxillary central
      incisor teeth performed in one and two appointments and the relationship, if any
      between pain and number of treatment visits. METHODS: The frequency of
      postobturation pain and swelling was recorded and evaluated over an observation
      period of 1 week in a 120 consecutive patients undergoing root canal treatment.
      The patients were assigned randomly into one of two groups of 60 patients each.
      The canals of all teeth were prepared and filled using the step-back preparation
      and lateral condensation filling techniques. The data were analyzed statistically
      using Mann-Whitney test. RESULTS: Eight of the 120 patients were excluded from
      the analysis as they failed to attend for postoperative reviews. Out of the 112
      patients involved in the study 90 patients had no pain, 9 patients had slight
      pain, 8 patients had moderate pain, and 5 patients had severe pain after 2 days.
      After 7 days 104 patients had no pain, 4 patients had slight pain, 3 patients had
      moderate pain and 1 patient had severe pain. CONCLUSIONS: No statistically
      significant difference in the incidence and degree of postoperative pain was
      found between one and two visit Endodontic procedures. The rate of post
      obturation flare up in asymptomatic Endodontically treated non vital maxillary
      centarl incisors was 11.6 and 3.6% after 2 and 7 days, respectively.

PMID- 16439047
TI  - Effect of xylitol:sorbitol on fluoride enamel demineralization reduction in situ.
AB  - OBJECTIVES: To evaluate if sugar alcohols would reduce enamel demineralization
      enhancing the fluoride (F) effect. METHODS: A crossover in situ study was
      conducted in four phases, during which 10 volunteers were submitted to one of the
      treatments: (I) Distilled and deionized water, as a negative control; (II) F (226
      microg F/ml as NaF; concentration used in commercial mouthrinse); (III) X:S
      (xylitol:sorbitol 1:3; final concentration 1.6M; 28% of sugar alcohols) and (IV)
      F+X:S (same final concentration that groups II and III). The volunteers wore
      palatal appliances containing four bovine enamel blocks of known surface
      microhardness (SMH), covered with a 'test plaque' of mutans streptococci, which
      were immersed during 1 min in one of the allocated treatment solutions
      simultaneously that the volunteers rinsed their mouths with the same solution.
      After the rinsing the appliances were put in the mouth and after 20 min a
      cariogenic challenge was made with 20% sucrose solution during 1 min. After
      further 45 min the 'test plaque' was collected for F analysis, enamel SMH was
      again determined and the percentage of change in relation to baseline was
      calculated; F uptake in enamel was also determined. RESULTS: With respect to all
      the analyses made, the group F+X:S did not differ from the F treatment (p>0.05)
      and the groups treated with F and F+X:S differed from the negative control
      (p<0.05). CONCLUSIONS: The results suggest that xylitol:sorbitol may not enhance
      the effect of fluoride present in mouth rinse on the reduction of enamel
      demineralization.

PMID- 16439048
TI  - Mechanical interactions of an implant/tooth-supported system under different
      periodontal supports and number of splinted teeth with rigid and non-rigid
      connections.
AB  - OBJECTIVES: This study investigated the mechanical interactions of implant-teeth
      splinting systems under different periodontal supports and number of splinted
      teeth with rigid and non-rigid connectors using non-linear finite element (FE)
      approach. METHODS: Two FE models with normal and compromised periodontal supports
      containing a Frialit-2 implant splinted to the first and second premolars were
      constructed. Non-linear contact elements were used to simulate a realistic
      interface fixation within the implant system and the sliding function of the non
      rigid connector. ANOVA was used to test for relative importance of the
      investigated factors and main effects for each level of the three investigated
      factors (periodontal supports, teeth splinting and connector designs) in terms of
      the stress values were performed. RESULTS: The simulated results indicated that
      the cross-interaction of the periodontal support and the splinting situation was
      a major factor affecting the stress value in alveolar bone. An additional
      splinting decreased the stress values of bone significantly for a compromised
      periodontal support. The individual factor of periodontal support also influenced
      the stress found in the alveolar bone (28%) and implant (72%), and the stress
      values increased when the periodontal support was reduced. Using different
      connectors affected the stresses found in bone (15%), implant (21%) and
      prosthesis (99%). The stress values of the implant and prosthesis increased, but
      were decreased in bone when the splinting system used non-rigid connectors. The
      mobility of natural teeth and the implant system between non-rigid and rigid
      connections showed only small differences. CONCLUSIONS: A non-rigid connector
      should be used with caution since it breaks the stress transfer and increases the
      unfavorable stress values in the implant system and prosthesis. The tooth/implant
      supported system with an additional splinting is more efficient in compromised
      periodontal supports.

PMID- 16439049
TI  - Specific coping strategies of Africans during urbanization: comparing
      cardiovascular responses and perception of health data.
AB  - Specific coping mechanisms of Africans during urbanization were compared to and
      correlated with cardiovascular responses and perception of health data. Subjects
      included men (N=286) and women (N=360). The COPE questionnaire classified
      subjects as active (AC) or passive (PC) copers and the General Health
      Questionnaire measured subjective perception of health. The Finapres recorded
      blood pressure continuously before and during application of a handgrip test.
      Analyses adjusting for age, body mass index and resting cardiovascular data
      revealed that AC rural subjects showed predominantly cardiac responses and PC
      rural subjects predominantly vascular responses. All urbanized African men and
      women showed higher resting blood pressure, vascular responsiveness and
      hypertension prevalences than their rural counterparts. All rural AC subjects,
      especially women, and all urban PC subjects, especially men, reported a poorer
      perception of health. In conclusion, subjects with a PC style showed a
      predominantly vascular response in rural and urban areas whereas subjects with an
      AC style seem to shift from a predominant cardiac output response to a
      predominant vascular resistance response when moving from a rural to an urban
      area.

PMID- 16439050
TI  - Development and internal validation of a nomogram predicting the probability of
      prostate cancer Gleason sum upgrading between biopsy and radical prostatectomy
      pathology.
AB  - OBJECTIVE: Previous reports indicate that as many as 43% of men with low grade
      PCa at biopsy will be diagnosed with high-grade PCa at RP. We explored the rate
      of upgrading from biopsy to RP specimen in our contemporary cohort, and developed
      a model capable of predicting the probability of biopsy Gleason sum upgrading.
      MATERIALS AND METHODS: The study cohort consisted of 2982 men treated with RP,
      with available clinical stage, serum prostate specific antigen and biopsy Gleason
      scores. These clinical data were used as predictors in multivariate logistic
      regression models (LRM) addressing the rate of Gleason sum upgrading between
      biopsy and RP pathology. LRM regression coefficients were used to develop a
      nomogram predicting the probability of Gleason sum upgrading and was subjected to
      200 bootstrap resamples for internal validation and to reduce overfit bias.
      RESULTS: Overall, 875 patients were upgraded (29.3%). In multivariate LRMs, all
      predictors were highly significant (all p values <0.0001). Bootstrap-corrected
      predictive accuracy of the nomogram predicting the probability of Gleason sum
      upgrading between biopsy and RP was 0.804. CONCLUSION: We developed a highly
      accurate clinical aid for treatment decision-making. It may prove useful when the
      possibility of a more aggressive Gleason variant may change the treatment
      options.

PMID- 16439051
TI  - Is penile enlargement an ethical procedure for patients with a normal-sized
      penis?

PMID- 16439053
TI  - Twenty years of urotherapy in children: what have we learned?

PMID- 16439052
TI  - Role of transurethral resection of the prostate and biopsy of the peripheral zone
      in the same session after repeated negative biopsies in the diagnosis of prostate
      cancer.
AB  - OBJECTIVE: To determine the role of the transurethral resection of the prostate
      (TURP) together with biopsies of the peripheral zone in the diagnosis of prostate
      cancer after repeated negative transrectal biopsies and increasing prostate
      specific antigen (PSA) levels. METHODS: From 2003 to 2004, 43 patients, aged 53
      69 yr, were seen for a history of at least two negative biopsies for prostate
      cancer. Thirty-five men had an increasing PSA level and underwent another set of
      biopsies. Seven patients had prostate cancer (20%); three were lost at follow-up
      and four had a Charlson comorbidity index >1. The remaining 21 were offered TURP
      and biopsy of the peripheral zone. Bladder outlet obstruction had no influence on
      decision-making. Fourteen men accepted. RESULTS: Eight patients (57%) had
      prostate cancer and underwent radical prostatectomy. Six cancers were detected
      only with TURP, one with TURP and biopsy, and one with biopsy alone. After a
      median of 9 mo of follow-up, two of six patients underwent rebiopsy for a rising
      PSA level, but no cancer was detected. CONCLUSIONS: TURP combined with a set of
      transrectal needle biopsies of the lateral portion of the gland is a safe
      procedure with a high diagnostic power after repeated negative biopsies in
      patients with persistently increasing PSA levels.

PMID- 16439054
TI  - Nomograms are more meaningful than severity-adjusted institutional comparisons
      for reporting outcomes.

PMID- 16439055
TI  - Evaluation of color Doppler in guiding prostate biopsy after HIFU ablation.
AB  - OBJECTIVE: Transrectal ultrasound cannot accurately depict early cancer
      recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. We
      evaluated transrectal color Doppler (CD) in guiding post-HIFU prostate biopsy.
      METHODS: Prostate CD-guided sextant biopsies were obtained in 82 patients who had
      undergone prostate HIFU ablation for cancer, 24 of whom had hormone therapy
      before the treatment. At the time of biopsy, a subjective CD score was given to
      all biopsy sites (0=no flow; 1=minimal flow; 2=suspicious flow pattern). CD
      findings were compared with biopsy results. RESULTS: CD was a significant
      predictor of biopsy findings, according to univariate and multivariate site-by
      site analysis. However, only 36 of 94 sites with residual cancer had positive CD
      findings, and thus, negative CD findings should not preclude random biopsy. There
      was a significant interaction between CD diagnostic capability and a history of
      hormone therapy before HIFU treatment. CD was a significant and independent
      predictor of biopsy findings in patients who had not received hormone therapy
      (odds ratio: 4.4; 95%CI: 2.5-7.9; p<0.0001), but not in those who had (odds
      ratio: 1.3; 95%CI: 0.5-3.4; p>0.5). CONCLUSION: Biopsy taken in CD-positive sites
      were 4.4 times more likely to contain cancer in patients who did not receive
      hormone therapy. CD could not reliably depict cancer recurrence in patients with
      history of hormone therapy.

PMID- 16439057
TI  - Density functional theory calculations for [C(2)H(4)N(2)O(6)]((n)) (n=0, +1, -1).
AB  - The structural and electronic properties of neutral and mono ionic structures of
      isolated ethylene glycol dinitrate (EGDN) [C(2)H(4)N(2)O(6)]((n)) (n=0, +1, -1)
      have been investigated by performing density functional theory calculations at
      B3LYP level. The optimum geometry, vibrational frequencies, electronic structure
      and some thermo dynamical values of the structures considered have been obtained
      in their ground states. The calculations reveal that as the charge develops the
      bond lengths and angles change. In the anionic case charge accumulation causes
      NO(2) elimination as a result of esteric O-N bond cleavage.

PMID- 16439058
TI  - Heap leaching of Cu contaminated soil with [S,S]-EDDS in a closed process loop.
AB  - Heap leaching of Cu contaminated soil (412+/-11 mg kg(-1)) with 5 mmol kg(-1)
      ethylenediamine disuccinate [S,S]-EDDS as a chelator was tested in a laboratory
      scale soil column study. The washing solution was recycled in a closed process
      loop after microbial (using a microbially active permeable bed, composed of
      substrate and absorbent) and oxidative chemical (using combined ozonation and UV
      irradiation) degradation of metal-[S,S]-EDDS complexes and retention of released
      Cu on a commercial absorbent Slovakite. Heap leaching using the permeable bed
      removed 25.5+/-3.6% of initial total Cu from the soil. Ozone/UV treatment of the
      [S,S]-EDDS washing solution removed much more, 47.5+/-7.4%, of Cu. Both methods
      yielded a clear and colorless final (waste) washing solution, with 7.0+/-10.0 and
      2.6+/-0.7 mg L(-1) Cu (permeable bed and ozone/UV method, respectively). The
      results of our study indicate that chemical treatment of chelator washing
      solution with ozone/UV in a closed process loop could lead to the development of
      a new, efficient and environmentally safe remediation method with controllable Cu
      emissions.

PMID- 16439056
TI  - Retroperitoneoscopic pyeloplasty for ureteropelvic junction obstruction (UPJO):
      solving the technical difficulties.
AB  - OBJECTIVES: To evaluate our current practice in retroperitoneoscopic pyeloplasty
      in patients with ureteropelvic junction obstruction (UPJO). Special interest was
      paid to technical difficulties associated with the retroperitoneoscopic approach.
      METHODS: Our retroperitoneoscopic approach for pyeloplasty is explained step for
      step including the most technically challenging part: the ureteropelvic
      anastomosis. RESULTS: Within 49 months a total of 47 retroperitoneoscopic
      pyeloplasties we performed at our institution. Before pyeloplasty an
      endopyelotomy had failed in five patients (11%). We did not necessarily perform a
      ventral transposition of the anastomosis in cases with a crossing vessel. Two
      (4%) conversions to open surgery were required because of scarring after previous
      endopyelotomy and massive obesity resulting in a limited working space. There
      were no intraoperative complications. A recurrence of UPJO was observed in 2% (n
      = 1). CONCLUSION: Functional results after retroperitoneoscopic pyeloplasty are
      excellent and comparable to those of open surgery. However, special knowledge of
      retroperitoneoscopy is necessary to provide the patient with a safe and effective
      minimally invasive alternative to open pyeloplasty.

PMID- 16439059
TI  - Enhanced adsorption of phenol from water by ammonia-treated activated carbon.
AB  - Influence of treatment with gaseous ammonia on adsorption properties toward
      phenol from water was examined for commercially available CWZ-series activated
      carbons. The treatment was carried out at elevated temperatures ranged from 400
      degrees C to 800 degrees C for 2 h. In comparison with untreated material,
      activated carbons modified with ammonia demonstrated enhanced adsorption of
      phenol from water. The enhancement depended on the treatment temperature and
      porous structure of studied activated carbons. Fourier transform infrared
      spectroscopy (FTIR) measurements confirmed presence of N-containing species in
      ammonia-treated activated carbons. Optimal conditions of the modification with
      ammonia were determined. Influence of the N-containing groups and porous
      structure of activated carbons on adsorption of phenol is discussed.

PMID- 16439060
TI  - Removal of chromium(III) from aqueous solutions using Lewatit S 100: the effect
      of pH, time, metal concentration and temperature.
AB  - The removal of the Cr(III) ion from aqueous solutions with the Lewatit S 100 ion
      exchange resin is described; and the performance of this resin was compared with
      Chelex-100 resin. The effect of adsorbent dose, initial metal concentration,
      contact time, pH and temperature on the removal of Cr(III) was investigated.
      Lewatit S 100 shows a remarkable increase in sorption capacity for Cr(III). The
      Batch ion-exchange process was relatively fast; and it reached equilibrium after
      about 150 min of contact. The ion-exchange process, which is pH dependent show
      maximum removal of Cr(III) in the pH range 2.8-4.0 for an initial Cr(III)
      concentration of 1.0 x 10(-3)M. The equilibrium constants were 36.67 at pH value
      3.5 for Lewatit S 100 and 6.64 at pH value 4.5 for Chelex-100 resin. Both of the
      resins had high-bonding constants. The equilibrium related to their ion-exchange
      capacity and the amount of the ion exchange was obtained by using the plots of
      the Langmuir adsorption isotherm. It was observed that the maximum ion-exchange
      capacity of 0.39 mmol of Cr(III)/g for Lewatit S 100 and 0.29 mmol of Cr(III)/g
      for Chelex-100 was achieved at optimum pH values of 3.5 and 4.5, respectively.
      The thermodynamic equilibrium constant and the Gibbs free energy flow were
      calculated for each system. The ion exchange of Cr(III) on these cation-exchange
      resins followed first-order reversible kinetics. The intra-particle diffusion of
      Cr(III) on ion-exchange resin represented the rate-limiting step. The rise in
      temperature caused a slight increase in the value of the equilibrium constant
      (K(c)) for the sorption of Cr(III) ion for both resins.

PMID- 16439061
TI  - Analysis of scanning probe microscope images using wavelets.
AB  - The utility of wavelet transforms for analysis of scanning probe images is
      investigated. Simulated scanning probe images are analyzed using wavelet
      transforms and compared to a parallel analysis using more conventional Fourier
      transform techniques. The wavelet method introduced in this paper is particularly
      useful as an image recognition algorithm to enhance nanoscale objects of a
      specific scale that may be present in scanning probe images. In its present form,
      the applied wavelet is optimal for detecting objects with rotational symmetry.
      The wavelet scheme is applied to the analysis of scanning probe data to better
      illustrate the advantages that this new analysis tool offers. The wavelet
      algorithm developed for analysis of scanning probe microscope (SPM) images has
      been incorporated into the WSxM software which is a versatile freeware SPM
      analysis package.

PMID- 16439062
TI  - Remnant epitopes, autoimmunity and glycosylation.
AB  - The role of extracellular proteolysis in innate and adaptive immunity and the
      interplay between cytokines, chemokines and proteinases are gradually becoming
      recognized as critical factors in autoimmune processes. Many of the involved
      proteinases, including those of the plasminogen activator and matrix
      metalloproteinase cascades, and also several cytokines and chemokines, are
      glycoproteins. The stability, interactions with inhibitors or receptors, and
      activities of these molecules are fine-controlled by glycosylation. We studied
      gelatinase B or matrix metalloproteinase-9 (MMP-9) as a glycosylated enzyme
      involved in autoimmunity. In the joints of rheumatoid arthritis patients, CXC
      chemokines, such as interleukin-8/CXCL8, recruit and activate neutrophils to
      secrete prestored neutrophil collagenase/MMP-8 and gelatinase B/MMP-9. Gelatinase
      B potentiates interleukin-8 at least tenfold and thus enhances neutrophil and
      lymphocyte influxes to the joints. When cartilage collagen type II is cleaved at
      a unique site by one of several collagenases (MMP-1, MMP-8 or MMP-13), it becomes
      a substrate of gelatinase B. Human gelatinase B cleaves the resulting two large
      collagen fragments into at least 33 peptides of which two have been shown to be
      immunodominant, i.e., to elicit activation and proliferation of autoimmune T
      cells. One of these two remnant epitopes contains a glycan which is important for
      its immunoreactivity. In addition to the role of gelatinase B as a regulator in
      adaptive immune processes, we have also demonstrated that it destroys interferon
      beta, a typical innate immunity effector molecule and therapeutic cytokine in
      multiple sclerosis. Furthermore, glycosylated interferon-beta, expressed in
      Chinese hamster ovary cells, was more resistant to this proteolysis than
      recombinant interferon-beta from bacteria. These data not only prove that
      glycosylation of proteins is mechanistically important in the pathogenesis of
      autoimmune diseases, but also show that targeting of glycosylated proteinases or
      the use of glycosylated cytokines seems also critical for the treatment of
      autoimmune diseases.

PMID- 16439063
TI  - Probing the substrate specificity of four different sialyltransferases using
      synthetic beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)
      (CH(2))7CH3 analogues general activating effect of replacing N-acetylglucosamine
      by N-propionylglucosamine.
AB  - The acceptor specificities of ST3Gal III, ST3Gal IV, ST6Gal I and ST6Gal II were
      investigated using a panel of beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D
      Manp-(1-->O)(CH(2))(7)CH(3) analogues. Modifications introduced at either C2, C3,
      C4, C5, or C6 of terminal D-Gal, as well as N-propionylation instead of N
      acetylation of subterminal D-GlcN were tested for their influence on the alpha
      2,3- and alpha-2,6-sialyltransferase acceptor activities. Both ST3Gal enzymes
      displayed the same narrow acceptor specificity, and only accept reduction of the
      Gal C2 hydroxyl function. The ST6Gal enzymes, however, do not have the same
      acceptor specificity. ST6Gal II seems less tolerant towards modifications at Gal
      C3 and C4 than ST6Gal I, and prefers beta-D-GalpNAc-(1-->4)-beta-D-GlcpNAc
      (LacdiNAc) as an acceptor substrate, as shown by replacing the Gal C2 hydroxyl
      group with an N-acetyl function. Finally, a particularly striking feature of all
      tested sialyltransferases is the activating effect of replacing the N-acetyl
      function of subterminal GlcNAc by an N-propionyl function.

PMID- 16439064
TI  - TFAM-dependent and independent dynamics of mtDNA levels in C2C12 myoblasts caused
      by redox stress.
AB  - TFAM is an essential protein factor for the initiation of transcription of the
      mtDNA. It also functions as a packaging factor, which stabilizes the mtDNA pool.
      To investigate the regulatory role of TFAM for regeneration and proliferation of
      the mtDNA pool, we exposed the muscle cell line C2C12 to a severe redox stress
      (H2O2) or to a moderate redox stress (GSH depletion), determined the dynamics of
      the mtDNA levels and correlated this with the TFAM protein levels. H2O2 caused a
      concentration-dependent loss of mtDNA molecules. The mtDNA levels recovered
      slowly within 3 days after H2O2 stress. The TFAM protein was less degraded than
      the mtDNA indicating an accumulation of TFAM protein per mtDNA after H2O2 stress.
      Overexpression of TFAM did not protect against the mtDNA loss after H2O2 stress
      but shortened the recovery time. GSH depletion led to a proliferation of the
      mtDNA pool. Although the mtDNA levels increased the TFAM protein levels were
      unaffected by the GSH depletion. We conclude that the accumulation of the TFAM
      protein after H2O2 stress contributes to the regeneration of the mtDNA pool but
      that other mechanisms, independent from the TFAM protein amount have to be
      postulated to explain the proliferation of the mtDNA pool after GSH depletion.

PMID- 16439065
TI  - Might calcium disorders cause or contribute to myoclonic seizures in epileptics?
AB  - Although epilepsy is not rare, many epileptic conditions are considered to be
      idiopathic and the related seizures of unknown origin. It does appear that
      different types of seizures are caused by differing mechanisms. This paper
      discusses scattered case reports involving problems with calcium metabolism and
      the thyroid, and/or the parathyroid glands concurrent with seizures that support
      the position that calcium control mechanisms may have been involved in causing
      seizures in those patients. This paper hypothesizes that calcium levels can
      cause, or at least contribute to myoclonic (jerk) seizures, as well as to
      possibly infantile spasms. As these conditions are difficult to treat medically,
      this paper suggests that nutritional interventions, such as supplemental calcium,
      magnesium and/or vitamin D, might well be considered as an option as a first-line
      treatment in those with these types of epileptic disorders. The nutritional
      recommendations also would apply for those who have seizures concurrent with Down
      syndrome.

PMID- 16439066
TI  - Immunoplacental therapy, a potential multi-epitope cancer vaccine.
AB  - The field of tumor immunology has made great advancements in recent years. A
      retrospective analysis of previous vaccine strategies combined with present
      knowledge may provide additional insight in this treatment modality. This article
      provides a review of immunoplacental therapy (IPT), a cancer vaccine consisting
      of chorionic villi extractions from the human placenta after a live full-term
      delivery. This therapy was first introduced in the 1970s by Valentin I. Govallo,
      M.D., Ph.D., who noted the immunological similarities between pregnancy and
      cancer. The goal of cancer immunotherapy, according to Govallo, is to view the
      fetal allograft as an "impregnating tumor" and create an immunological state in
      the oncological patient analogous to a spontaneous abortion in a pregnant women.
      The placenta shares identical growth mechanisms, antigenic determinants, and
      immune-escape properties with cancer cells; this includes numerous tumor
      associated antigens, angiogenic growth factors, complement regulatory proteins,
      and defective apoptotic mechanisms which aid in their survival. Placental
      vaccination may function as a multi-epitope vaccine; the body recognizes the
      placental antigens of this vaccine as foreign, and thus stimulates a cross
      reactive humoral and cell-mediated immune response targeting cancer tumor
      associated antigens as well as proteins that aid in cancer angiogenesis,
      complement regulation, and apoptotic resistance. With recent advancements in
      molecular and cellular cancer immunology, the model introduced by Govallo may
      provide an important strategic approach to cancer immunotherapy.

PMID- 16439067
TI  - Tannins from barks of Pinus caribaea protect Escherichia coli cells against DNA
      damage induced by gamma-rays.
AB  - This work was aimed to evaluate genotoxicity and antigenotoxicity activity
      against gamma-rays of a tannin fraction obtained from barks of Pinus caribaea, as
      well as to elucidate the antigenotoxic mechanisms involved in radioprotection by
      using different approaches as pre-, co- and post-irradiation cell treatments with
      plant extract. The tannin fraction was not genotoxic to Escherichia coli cells in
      experiments using different exposure times. This extract was antigenotoxic
      against gamma-rays when the cells were pre- or co-treated with this extracts, but
      not during post-irradiation treatments, suggesting a possibly antigenotoxic
      action through free radical scavenging mechanisms. The results are discussed in
      relation to the chemopreventive and therapeutic potential of the studied plant
      species.

PMID- 16439068
TI  - Intronic breakpoint definition and transcription analysis in DMD/BMD patients
      with deletion/duplication at the 5' mutation hot spot of the dystrophin gene.
AB  - Dystrophin mutations occurring at the 5' end of the gene frequently behave as
      exceptions to the "frame rule," their clinical severity being variable and often
      not related to the perturbation of the translation reading frame. The molecular
      mechanisms underlying the phenotypic variability of 5' dystrophin mutations have
      not been fully clarified. We have characterized the genomic breakpoints within
      introns 2, 6 and 7 and identified the splicing profiles in a cohort of DMD/BMD
      patients with deletion of dystrophin exons 3-7, 3-6 and duplication of exons 2-4.
      Our findings indicate that the occurrence of intronic cryptic promoter as well as
      corrective splicing events are unlikely to play a role in exons 3-7 deleted
      patients phenotypic variability. Our data suggest that re-initiation of
      translation could represent a major mechanism responsible for the production of a
      residual dystrophin in some patients with exons 3-7 deletion. Furthermore, we
      observed that the out-of-frame exon 2a is almost constantly spliced into a
      proportion of the dystrophin transcripts in the analysed patients. In the exons 2
      4 duplicated DMD patient, producing both in-frame and out-of-frame transcripts,
      this splicing behaviour might represent a critical factor contributing to the
      severe phenotype. In conclusion, we suggest that multiple mechanisms may have a
      role in modulating the outcome of 5' dystrophin mutations, including recoding
      mechanisms and unusual splicing choices.

PMID- 16439069
TI  - Gene by environment interactions and the development of asthma and allergy.
AB  - Asthma is the most common chronic disease during childhood in modern societies.
      Prevalence rates differ between countries, but on an average, 10-20% of the
      children in Western Europe and the US are affected. While the true cause of the
      disease is not yet known, it is common perception that genetic alterations and
      environmental factors act together in the development of atopic diseases such as
      asthma, allergic rhinitis and atopic eczema. Numerous studies have reported an
      association between environmental tobacco smoke (ETS) exposure and respiratory
      diseases: maternal smoking during pregnancy and early childhood is associated
      with impaired lung growth and diminished lung function, and in asthmatic children
      parental smoking increases symptoms and the frequency of asthma attacks. Recent
      studies have shown that the capability of ETS to induce asthma and asthma
      symptoms may be modified by genetics. Linkage studies, which took smoking and
      passive smoking status of study subjects into account, came to different results
      than those studies based on unstratified samples. These analyses indicated that
      some chromosomal regions (e.g. 5q) might harbor genes that exert their effects
      predominantly in combination with ETS exposure. Some of the genes modifying the
      effect of ETS and air pollution on the body may have been identified. When these
      detoxification enzymes are genetically defect or missing the capability of the
      lung to metabolize hazardous substances is dramatically diminished. As a
      consequence, pulmonary inflammation may occur and the barrier function of the
      lung may be compromised allowing allergens to penetrate and asthma to start.
      Knowledge of these interactions may be the key in understanding the complex
      nature of the disease. It may allow for prediction and an earlier diagnosis of
      the disease as well as better and more efficient prevention. In the long run, it
      may contribute significantly to the development of new and better-tailored drugs
      for one of the major diseases of the 21st century.

PMID- 16439070
TI  - Cognitive behavior therapy for menopausal hot flashes: two case reports.
AB  - Two case reports of women treated with an individual cognitive behavioral
      treatment (CBT) for menopausal hot flashes are presented. Both women reported
      substantial improvements in the number of hot flashes experienced as well as in
      their quality of life as measured by the Menopause Quality of Life Scale
      (MENQOL), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton
      Rating Scale for Anxiety (HAM-A). Improvements in hot flashes and quality of life
      were maintained 6 months after treatment ended. It is hypothesized that CBT
      reduces hot flashes by reducing central sympathetic activation, perceptions of
      stress, and self-critical thoughts. The long-term efficacy of CBT for hot flashes
      should be examined in large controlled clinical trials.

PMID- 16439071
TI  - Niosomes as carriers for tretinoin. III. A study into the in vitro cutaneous
      delivery of vesicle-incorporated tretinoin.
AB  - The influence of drug thermodynamic activity and niosome composition, size,
      lamellarity and charge on the (trans)dermal delivery of tretinoin (TRA) was
      studied. For this purpose, tretinoin was incorporated at saturated and
      unsaturated concentrations in both multilamellar (MLV) and unilamellar (UV)
      vesicular formulations using two different commercial mixtures of alkyl
      polyglucosides: octyl-decyl polyglucoside and decyl polyglucoside. Positively and
      negatively charged vesicular formulations were prepared using either stearylamine
      or dicetylphosphate as a charge inducer. Niosomes made with polyoxyethylene (4)
      lauryl ether and liposomes made with soy phosphatidylcholine were also prepared
      and studied. Vesicular formulations were characterised by transmission electron
      microscopy and optical and light polarized microscopy for vesicle formation and
      morphology, and by dynamic laser light scattering for size distribution. The
      effect of the vesicular incorporation of tretinoin on its (trans)dermal delivery
      through the newborn pig skin was also investigated in vitro using Franz cells, in
      comparison with a commercial formulation of the drug (RetinA). The amount of
      tretinoin delivered through and accumulated in the several skin layers was
      detected by HPLC. Overall, obtained results showed that tretinoin cutaneous
      delivery is strongly affected by vesicle composition and thermodynamic activity
      of the drug. In particular, small, negatively charged niosomal formulations,
      which are saturated with tretinoin, have shown to give higher cutaneous drug
      retention than both liposomes and commercial formulation. Moreover, interactions
      between skin and vesicles seem to depend on physico-chemical properties of the
      main component of the vesicular bilayer.

PMID- 16439073
TI  - Production of GMP-grade radioactive holmium loaded poly(L-lactic acid)
      microspheres for clinical application.
AB  - Radioactive holmium-166 loaded poly(L-lactic acid) microspheres are promising
      systems for the treatment of liver malignancies. The microspheres are loaded with
      holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method.
      After preparation, the microspheres (Ho-PLLA-MS) are activated by neutron
      irradiation in a nuclear reactor. In this paper, the aspects of the production of
      a (relatively) large-scale GMP batch (4 g, suitable for treatment of 5-10
      patients) of Ho-PLLA-MS are described. The critical steps of the Ho-PLLA-MS
      production process (sieving procedure, temperature control during evaporation and
      raw materials) were considered and the pharmaceutical quality of the microspheres
      was evaluated. The pharmaceutical characteristics (residual solvents, possible
      bacterial contaminations and endotoxins) of the produced Ho-PLLA-MS batches were
      in compliance with the requirements of the European Pharmacopoeia. Moreover,
      neutron irradiated Ho-PLLA-MS retained their morphological integrity and the
      holmium remained stably associated with the microspheres; it was observed that
      after 270h (10 times the half-life of Ho-166) only 0.3+/-0.1% of the loading was
      released from the microspheres in an aqueous solution. In conclusion, Ho-PLLA-MS
      which are produced as described in this paper, can be clinically applied, with
      respect to their pharmaceutical quality.

PMID- 16439072
TI  - Development of liposomal capreomycin sulfate formulations: effects of formulation
      variables on peptide encapsulation.
AB  - PURPOSE: The aim of this work was the investigation of the effects of preparation
      variables on drug content for the development of capreomycin sulfate (CS)
      liposomal formulations as potential aerosol antitubercular agents. METHODS:
      Dipalmitoylphosphatidylcholine (DPPC), hydrogenated phosphatidylcholine (HPC) and
      distearoylphosphatidylcholine (DSPC) were used for liposome preparation. A freeze
      thawing method was chosen for CS encapsulation. Peptide entrapment, size and
      morphology were evaluated by UV spectrophotometry, photocorrelation spectroscopy
      (PCS) and transmission electron microscopy (TEM), respectively. A 2(3) full
      factorial protocol was designed to evaluate the conditions for CS encapsulation
      improvement. RESULTS: Peptide content ranged between 1 and 8%. Vesicles showed a
      narrow size distribution, with average diameters around 1 microm and a good
      morphology. A mathematical model was generated for each liposomal system and
      check point analyses revealed good agreement between experimental and predicted
      values. DPPC liposomes were found to provide the highest CS content. CONCLUSIONS:
      Peptide content was successfully increased by assessing formulation variable
      effects using a 2(3) factorial design that proved to be a time saving method
      helpful in developing new CS liposomal formulations for a possible application in
      aerosol antitubercular therapies.

PMID- 16439074
TI  - Pharmacokinetic and pharmacodynamic studies following oral administration of
      erythropoietin mucoadhesive tablets to beagle dogs.
AB  - Oral administration of mucoadhesive tablets containing erythropoietin (EPO) and
      an absorption enhancer Labrasol was studied in rats and dogs. Mucoadhesive
      tablets were prepared using Sylysia 550 holding the absorption enhancer and
      Carbopol 974P as a mucoadhesive agent. Mucoadhesive tablets were covered with a
      water-insoluble backing layer made of cellulose acetate and a pH-sensitive
      covering layer made of Eudragit L/Eudragit S. Tablet was administered into the
      rat jejunum at EPO dose of 100 IU/kg and serum samples were collected for 6h.
      Serum EPO level was analysed with a standard ELISA procedure. After
      administration, rats showed a maximum serum EPO level of C(max) 70.6 +/- 8.9
      mIU/ml. Oral administration of a single tablet containing 100 IU/kg EPO to beagle
      dogs showed a C(max) of 24.6 +/- 4.1. When EPO dose was increased to 500 IU/kg
      and the number of tablets was also increased to 5, the C(max) was 54.8 +/- 9.0
      mIU/ml. However, when EPO, 100 IU/kg dose was divided into five tablets, the
      C(max) was 15.5 +/- 1.8 mIU/ml. In the absence of absorption enhancer, the C(max)
      was 35.8 +/- 3.8 with 500 IU/kg dose distributed among five tablets.
      Pharmacodynamic studies were carried out following oral administration of
      mucoadhesive tablets for 6 consecutive days at an EPO dose of 500 IU/kg. Whole
      blood samples were collected and percent circulating reticulocytes were counted
      using Miller technique. The increase in percent circulating reticulocytes was
      found to be 1.7% on day 8 following oral administration. As a control study, EPO
      was administered by i.v. route at a dose of 300 IU/kg for 3 consecutive days and
      the percent circulating reticulocytes were counted. Mucoadhesive tablets showed
      promising results as an oral drug delivery system for protein therapeutics.

PMID- 16439075
TI  - In vitro studies on the application of colloidal emulsion aphrons to drug
      overdose treatment.
AB  - Colloidal emulsion aphrons (CEAs) are considered as the micron-sized water-in-oil
      (W/O) emulsion-cores encapsulated by a "soapy shell" consisting of multi-layer
      surfactant molecules. In this dispersion, the emulsion-core sizes are mainly in
      10-100 microm and that of the inner phase droplets are in 1-5 microm. CEAs not
      only behave analogously to emulsion liquid membrane (ELM) in extraction with
      advantages of high concentration ratio, counter-concentration extraction and
      combination of extraction with backwash together, but also have the large
      interface areas, easy scatteration and quick extraction which colloidal liquid
      aphrons (CLAs) possess. CEA extraction overcomes the restriction of partition
      equilibrium between the water and the oil phase that CLAs have. They have greater
      extraction capacity than CLAs. In this study, the application of CEAs to drug
      overdose treatment was studied using salicylic acid as the model drug, paraffin
      oil as the membrane phase, PEG-30 dipolyhydroxystearate (P135) as the hydrophobic
      surfactant, nonylphenol ethoxylate-10 (NP10) as the hydrophilic surfactant and
      NaOH solution as the receptor phase. Also some factors affecting the stability of
      this dispersion and extraction ratio were investigated. In order to prepare CEAs
      successfully, the concentrations of NP10 and P135 should be in 1.5-3.0% (w/v) and
      0.25-1.0% (w/v), respectively, together with the ratio of the volume of oil phase
      to the volume of inner aqueous phase of CEAs, R(oi)> or =1:1. For the extraction
      of salicylic acid, the pH value of the feed phase was supposed to be lower than
      2.0 and the suitable NaOH concentration of the receptor phase was higher than
      0.02 mol/L. Under this condition, more than 98.7% of salicylic acid was
      transported into receptor phase in half a minute.

PMID- 16439076
TI  - Cryo-TEM investigation of phase behaviour and aggregate structure in dilute
      dispersions of monoolein and oleic acid.
AB  - Cryo-transmission electron microscopy (cryo-TEM) was used to image the
      microstructure in dilute sonicated dispersions of monoolein and oleic acid. The
      aim of the study was to explore how different experimental parameters, such as
      sample composition, total lipid concentration, pH, and ageing affect the phase
      behaviour and aggregate structure. Our investigations show that a rich variety of
      lamellar and non-lamellar structures, including liposomes and particles of cubic
      and inverted hexagonal phase, may form depending on the experimental conditions.
      The results are analyzed and discussed in relation to existing phase diagrams and
      earlier investigations concerning phase- and structural behaviour in
      monoolein/oleic acid/water systems.

PMID- 16439077
TI  - Effect of vehicles and enhancers on the topical delivery of cyclosporin A.
AB  - Topical delivery of cyclosporin a (CysA) is of great interest for the treatment
      of autoimmune skin disorders. The purpose of this study was to investigate the
      effect of various vehicles and enhancers on the topical delivery across rat skin.
      The topical (to the skin) delivery of CysA was evaluated in vitro using rat skin
      mounted in a Franz diffusion cell. CysA was analyzed by UV-HPLC. As vehicles,
      CysA vehicle containing 40% ethanol showed significantly enhanced deposition of
      CysA into the stratum corneum (SC) and deeper skin, as compared to other
      vehicles. The efficiency of the vehicles to improve the topical delivery of CysA
      was sequenced in the order of: 40% ethanol>ethyl oleate>Transcutol>isopropyl
      myristate>ethanol>Labrasol>propylene glycol>Lauroglycol FCC. Next, we tested
      effect of pre-treatment with chemical enhancers on the penetration of CysA. The
      permeation-enhancer effect of enhancers was in the following order: 10% menthol
      approximately 0.05% SLS>5% Azone>5% NMP>5% DEMO. Moreover, chemical enhancers
      shortened the lag time of the penetration of CysA into deeper skin. The present
      study suggests that the suspension of 40% ethanol containing 0.5% drug can more
      effectively enhance the topical delivery of CysA after skin pre-treatment with
      10% menthol or 0.05% SLS.

PMID- 16439078
TI  - Lateral asymmetry in the ABR of neonates: evidence and mechanisms.
AB  - Lateralized processing of auditory stimuli occurs at the level of the auditory
      cortex but differences in function between the left and right sides are not clear
      at lower levels of the auditory system. The current study is designed to (1)
      investigate asymmetric auditory function at the ear and brainstem in human
      infants and (2) investigate possible mechanisms for asymmetry at these levels.
      Study 1 evaluated auditory brainstem responses (ABRs) in response to high and low
      level clicks presented to the right and left ears of neonates. Wave V was
      significantly larger in amplitude and waves III and V were shorter in latency
      when the ABR was generated in the right ear. Study 2 investigated two possible
      mechanisms of such asymmetry by (a) using contralateral white noise masking to
      activate the medial olivocochlear system and (b) increasing stimulus rate to
      reveal neural conduction and synaptic mechanisms. ABR wave V, evoked by clicks to
      the left ear, showed a greater reduction in amplitude with contralateral noise
      than the response evoked from the right ear. No systematic asymmetries in ABR
      latencies or amplitudes were found with increased stimulus rate. We conclude that
      (1) the click-evoked ABR in neonates demonstrates asymmetric auditory function
      with a small but significant right ear advantage and (2) asymmetric activation of
      the medial olivocochlear system, specifically greater contralateral suppression
      of ABR produced by the left ear, is a possible mechanism for asymmetry.

PMID- 16439080
TI  - Contextual modulation of cochlear hearing desensitization depends on the type of
      loud sound trauma.
AB  - In ears in which cochlear efferent pathways were cut and with testing done under
      anaesthetic conditions that preclude middle ear muscle activity (so as to examine
      the "intrinsic" effects of loud sound on the cochlea without any confounding
      effect of efferent pathways to the auditory periphery), atraumatic background
      white noise (WN) increases cochlear hearing loss (temporary threshold shifts,
      TTSs) induced by a traumatic pure tone but reduces TTSs caused by traumatic 5-kHz
      wide narrow band (NB) sound. The short-duration moderately intense traumata used
      in these studies most likely cause TTSs by affecting cochlear mechanics and these
      WN modulatory effects, exerted directly on the cochlea's intrinsic susceptibility
      to TTSs, are not predicted by any current description of cochlear mechanics. Here
      it is demonstrated that background WN reduces trauma-induced TTSs with even a
      relatively small increase in trauma bandwidth beyond that of a pure tone,
      discounting the alternative that contextual modulatory effects transition
      systematically along a continuum as trauma bandwidth increases from a pure tone
      to a broader bandwidth (albeit 2 kHz-wide NB) trauma. These results have
      implications for cochlear mechanics as the TTSs due to the traumatic sound of
      this study are most likely due to changes in cochlear mechanics but are not
      easily explained by what is currently known of cochlear mechanics.

PMID- 16439079
TI  - Geometry of the semicircular canals of the chinchilla (Chinchilla laniger).
AB  - The orientations of the semicircular canals determines the response of the canals
      to head rotations and, in turn, the brain's ability to interpret those motions.
      The geometry of chinchillas' semicircular canals has never been reported.
      Volumetric representations of three chinchilla skulls were generated using a
      microCT scanner. The centroids of each semicircular canal lumen were identified
      as they passed through the image slices and were regressed to a plane. Unit
      vectors normal to the plane representing canal orientations were used to
      calculate angles between canal pairs. Pitch and roll maneuvers required to bring
      any canal into the horizontal plane for physiologic investigation were
      calculated. The semicircular canals of the chinchilla were found to be relatively
      planar. The horizontal canal was found to be oriented 55.0 degrees anteriorly
      upward. Pairs of ipsilateral chinchilla canals were not orthogonal and
      contralateral synergistic pairs were not parallel. Despite this arrangement, the
      canal plane unit normal vectors were organized to respond with approximately
      equal overall sensitivity to rotations in any direction. The non-orthogonal
      chinchilla labyrinth may provide an opportunity to determine whether the frame of
      reference used by the central vestibular and oculomotor system is based on
      directions of afferent maximum sensitivity or prime directions.

PMID- 16439081
TI  - Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts:
      implication for its use in PMS.
AB  - The dried ripe fruit of Vitex agnus-castus L. (VAC) is widely used for the
      treatment of premenstrual syndrome (PMS). A previous study reported that extracts
      of VAC showed affinity to opiate receptors; however, functional activity was not
      determined. We tested two different VAC extracts in receptor binding and
      functional assays. Our objectives were: (1) to confirm the opiate affinity; (2)
      to rule out interference by free fatty acids (FFA); (3) to determine the mode of
      action of VAC at the mu-opiate receptor. Methanol extracts of VAC were prepared
      either before (VAC-M1) or after (VAC-M2) extraction with petroleum ether to
      remove fatty acids. Both extracts showed significant affinities to the mu-opiate
      receptor, as indicated by the concentration-dependent displacement of [3H]DAMGO
      binding in Chinese hamster ovary (CHO)-human mu-opiate receptor (hMOR) cells. The
      IC50 values were estimated to be 159.8 microg/ml (VAC-M1) and 69.5 microg/ml (VAC
      M2). Since the defatted extract not only retained, but exhibited a higher
      affinity (p<0.001), it argued against significant interference by fatty acids. In
      an assay to determine receptor activation, VAC-M1 and VAC-M2 stimulated
      [35S]GTPgammaS binding by 41 and 61% (p<0.001), respectively. These results
      suggested for the first time that VAC acted as an agonist at the mu-opiate
      receptor, supporting its beneficial action in PMS.

PMID- 16439083
TI  - The value of examination aids in victim identification: a retrospective study of
      an airplane crash in Nepal in 2002.
AB  - After the crash of an airplane in Nepal in the year 2002, the dental status of
      the 14 European victims was examined at autopsy as well as after additional
      removal of the soft tissue and compared with antemortem findings which were
      available in 11 cases. Re-examination of all jaws showed that nine composite
      fillings and seven root fillings as well as one parapulpal pin could not be
      detected during autopsy. Because tooth-coloured restorations may be overseen even
      by an experienced expert, the findings underline the necessity of performing a
      full resection of both jaws and removal of the soft tissue. Furthermore, X-ray
      analysis of the jaws and the use of phosphoric acid or ultra violet radiation for
      recognizing tooth-coloured restorations are recommended.

PMID- 16439082
TI  - Time of death dependent criteria in vitreous humor: accuracy of estimating the
      time since death.
AB  - Since more than 40 years reports on the rise of potassium concentration [K(+)] in
      vitreous humor have been published with different statements concerning the
      accuracy of death time estimation. In the last years several statistical
      approaches for a more accurate estimation of the time since death have been
      reported. While in most investigations the PMI has been used as the independent
      and [K(+)] as the dependent variable in linear regression analysis between PMI
      and [K(+)], recently it has been suggested to use [K(+)] as the independent
      variable for regression analysis. Changing the variables would lead to a higher
      accuracy of death time estimation. This has also been recommended for regression
      analysis between hypoxanthine concentration [Hx] and time since death. This
      hypothesis has been checked on independent cases with potassium and hypoxanthine
      in vitreous humor. Linear regression with [K(+)] or [Hx] as independent variable
      has revealed a slightly more accurate death time estimation compared to a linear
      regression with PMI as independent variable. Thus, e.g. the accuracy could have
      been improved from +/-25.96 to +/- 23.27h by using [K(+)] as independent
      variable. Another statistical approach has re-evaluated six large studies on the
      rise of vitreous [K(+)] using a local regression analysis (Loess procedure).
      Based on this re-evaluation an accuracy of death time estimation has been
      recommended (95% limits of confidence of +/-1h in the early PMI and +/-10h, 110h
      postmortem) which has surpassed even optimistic results of earlier
      investigations. This recommended accuracy of death time estimation has been
      checked on a random sample of 492 cases. Only 153 cases have been within the
      predicted postmortem interval, 339 lay outside with a systematic overestimation
      of the time since death.

PMID- 16439084
TI  - Cluster analysis of a forensic population with antisocial personality disorder
      regarding PCL-R scores: differentiation of two patterns of criminal profiles.
AB  - Fifty six cases of a forensic population were submitted to a cluster analysis to
      observe the aglomerative behavior in relation to the total scores of the items
      comprising the PCL-R Psychopathy Checklist Revised [R.D. Hare, Manual for the
      Hare Psychopathy Checklist-Revised, Multi-Health System, Toronto, 1991]. The
      analysis indicated two independent types of antisocial personality disorders, not
      identified in the PCL-R in its standardized form, one of them being strongly
      associated with criminal conduct and the other with psychopathic personality.
      Such clusters were stable when the analysis was replicated with other
      hierarchical algorithms, and also, they were independently extracted via the k
      means method without having previously fixed the value for k. One of the clusters
      concentrated the PCL-R highest scores, indicating that it is the prototypical
      psychopathic character determinant.

PMID- 16439085
TI  - Death scene evaluation in a case of fatal accidental carbon monoxide toxicity.
AB  - Exposure of humans to high concentrations of carbon monoxide can result in death,
      due to the formation of carboxyhaemoglobin (COHb), which impairs the oxygen
      carrying capacity of the haemoglobin. Carbon monoxide is responsible of a great
      number of accidental domestic poisonings and deaths throughout the world,
      particularly in homes that have faulty or poorly vented combustion appliances. A
      case is reported, in which a 21-year-old woman was found dead, due to carbon
      monoxide poisoning from a gas water heater, despite the puzzling evidence that
      the heater has been used for more than 10 years without any problem. An
      evaluation of the exposure to CO was performed, by measuiring the rate of
      production of CO from the heater, and using the Coburn-Forster-Kane equation to
      describe the kinetics of the poisoning process. The death was attributed to an
      accidental poisoning from carbon monoxide due to a sum of unfortunate
      circumstances.

PMID- 16439086
TI  - Y-chromosomal STR haplotypes in a population from the Amazon region, Brazil.
AB  - Haplotype and allele frequencies of the nine Y-STR (DYS19, DYS389 I, DYS389 II,
      DYS390, DYS391, DYS392, DYS393, DYS385 I/II) were determined in a population
      sample of 200 unrelated males from Belem, Brazil. The most common haplotypes are
      shared by 1.5% of the sample, while 186 haplotypes are unique. The haplotype
      diversity is 0.9995+/-0.0006. The data obtained were compared to those of other
      Brazilian populations. AMOVA indicates that 99.91% of all the haplotypical
      variation is found within geopolitical regions and only 0.09% is found among
      regions.

PMID- 16439087
TI  - A case of calcific retropharyngeal tendinitis suspected to be a retropharyngeal
      abscess upon the first medical examination.
AB  - We report a case of calcific retropharyngeal tendonitis that was difficult to
      distinguish from retropharyngeal abscess. The patient was a 34-year-old woman who
      complained of severe cervical pain and stiffness for 1 day. She had a fever and
      moderately elevated WBC. Fine needle aspiration of the swollen region of the
      retropharyngeal wall could not elucidate the pus characteristics. Enhanced CT
      scan showed no signs of an abscess, but clearly showed calcifications in front of
      the C1-2 cervical spine. An emergency drainage operation was avoided, and the
      patient fully recovered after treatment with NSAIDs and steroids.

PMID- 16439088
TI  - In vitro MRI of brain development.
AB  - In this review, we demonstrate the developmental appearance, structural features,
      and reorganization of transient cerebral zones and structures in the human fetal
      brain using a correlative histological and MRI analysis. The analysis of
      postmortem aldehyde-fixed specimens (age range: 10 postovulatory weeks to term)
      revealed that, at 10 postovulatory weeks, the cerebral wall already has a
      trilaminar appearance and consists of: (1) a ventricular zone of high cell
      packing density; (2) an intermediate zone; (3) the cortical plate (in a stage of
      primary consolidation) with high MRI signal intensity. The anlage of the
      hippocampus is present as a prominent bulging in the thin limbic telencephalon.
      The early fetal telencephalon impar also contains the first commissural fibers
      and fornix bundles in the septal area. The ganglionic eminence is clearly visible
      as an expanded continuation of the proliferative ventricular zone. The basal
      ganglia showed an initial aggregation of cells. The most massive fiber system is
      in the hemispheric stalk, which is in continuity with thalamocortical fibers.
      During the mid-fetal period (15-22 postovulatory weeks), the typical fetal
      lamination pattern develops and the cerebral wall consists of the following
      zones: (a) a marginal zone (visible on MRI exclusively in the hippocampus); (b)
      the cortical plate with high cell-packing density and high MRI signal intensity;
      (c) the subplate zone, which is the most prominent zone rich in extracellular
      matrix and with a very low MRI signal intensity; (d) the intermediate zone (fetal
      "white matter"); (e) the subventricular zone; (f) the periventricular fiber-rich
      zone; (g) the ventricular zone. The ganglionic eminence is still a very prominent
      structure with an intense proliferative activity. During the next period (22-26
      postovulatory weeks), there is the developmental peak of transient MRI features,
      caused by the high content of hydrophyllic extracellular matrix in the subplate
      zone and the accumulation of waiting afferent axons. The period between 27 and 30
      postovulatory weeks is characterized by gradual blurring of the laminar structure
      in parallel with the formation of cerebral convolutions. In near-term preterm
      infants, T2-weighted MR images showed better contrast resolution than T1-weighted
      images. We conclude that transient fetal zones and subcortical structures display
      characteristic MRI features due to the high content of extracellular matrix in
      the subplate zone, higher MRI signal intensity of zones with high cell-packing
      intensity, and the presence of growing fibers.

PMID- 16439089
TI  - Imaging in scoliosis from the orthopaedic surgeon's point of view.
AB  - For treating patients with scoliosis orthopaedic surgeons need diagnostic imaging
      procedures in order to provide answers about a possible underlying disease,
      choice of treatment, and prognosis. Once treatment is instituted, imaging is also
      critical for monitoring changes of the deformity so as to optimize therapy. The
      combined effort of orthopaedic surgeons and radiologists helps detect treatable
      causes of scoliosis at an early stage, define the need and timing for surgery,
      and ensure that every precaution is taken to minimize the risks of surgery.
      Neurosurgical causes, with particular reference to spinal cord tumours and
      syringomyelia, need to be addressed before scoliosis surgery can be contemplated.

PMID- 16439090
TI  - Diagnostic strategies in spinal trauma.
AB  - Spinal injuries may result in severe neurological deficits, especially if nerve
      roots or even the spinal cord are affected. Besides presenting the important
      anatomical and technical basis underlying the imaging findings of spinal
      injuries, the trauma mechanisms and the resulting injuries are discussed. Based
      on the current literature and recommendations of scientific organizations, an
      approach is provided to the radiologic work up of spinal trauma. The different
      imaging modalities are presented. Advantages and disadvantages of the methods are
      discussed.

PMID- 16439091
TI  - Quantitative parameters of image quality in 64-slice computed tomography
      angiography of the coronary arteries.
AB  - We explored quantitative parameters of image quality in consecutive patients
      undergoing 64-slice multi-detector computed tomography (MDCT) coronary
      angiography for clinical reasons. Forty-two patients (36 men, mean age 61 +/- 11
      years, mean heart rate 63 +/- 10 bpm) underwent contrast-enhanced MDCT coronary
      angiography with a 64-slice scanner (Siemens Sensation 64, 64 mm x 0.6 mm
      collimation, 330 ms tube rotation, 850 mAs, 120 kV). Two independent observers
      measured the overall visualized vessel length and the length of the coronary
      arteries visualized without motion artifacts in curved multiplanar reformatted
      images. Contrast-to-noise ratio was measured in the proximal and distal segments
      of the coronary arteries. The mean length of visualized coronary arteries was:
      left main 12 +/- 6 mm, left anterior descending 149 +/- 25 mm, left circumflex 89
      +/- 30 mm, and right coronary artery 161 +/- 38 mm. On average, 97 +/- 5% of the
      total visualized vessel length was depicted without motion artifacts (left main
      100 +/- 0%, left anterior descending 97 +/- 6%, left circumflex 98 +/- 5%, and
      right coronary artery 95 +/- 6%). In 27 patients with a heart rate < or = 65 bpm,
      98 +/- 4% of the overall visualized vessel length was imaged without motion
      artifacts, whereas 96+/-6% of the overall visualized vessel length was imaged
      without motion artifacts in 15 patients with a heart rate > 65 bpm (p < 0.001).
      The mean contrast-to-noise ratio in all measured coronary arteries was 14.6 +/-
      4.7 (proximal coronary segments: range 15.1 +/- 4.4 to 16.1 +/- 5.0, distal
      coronary segments: range 11.4 +/- 4.2 to 15.9 +/- 4.9). In conclusion, 64-slice
      MDCT permits reliable visualization of the coronary arteries with minimal motion
      artifacts and high CNR in consecutive patients referred for non-invasive MDCT
      coronary angiography. Low heart rate is an important prerequisite for excellent
      image quality.

PMID- 16439092
TI  - Rapid determination of clindamycin in medicine with myoglobin-luminol
      chemiluminescence system.
AB  - A sensitive chemiluminescence method, based on the inhibitory effect of
      clindamycin on the chemiluminescence reaction between luminol and myoglobin in a
      flow-injection system, is proposed for the determination of clindamycin. The
      decrement of chemiluminescence intensity is linear with the logarithm of
      clindamycin concentration over the range from 0.1 to 70.0 ng ml-1 (r2=0.9995),
      with the detection limit of 0.03 ng ml-1 (3sigma). At a flow rate of 2.0 ml min
      1, a complete analytical process could be performed within 0.5 min, including
      sampling and washing, with a relative standard deviation of less than 3.0% (n=5).
      The proposed procedure was applied successfully to the determination of
      clindamycin in capsules without any pretreatment process.

PMID- 16439093
TI  - Real-time RT-PCR quantification of pregnancy-associated plasma protein-A mRNA
      abundance in bovine granulosa and theca cells: effects of hormones in vitro.
AB  - Ovarian follicular growth and dominance are controlled by a series of hormonal
      and intraovarian events including a decrease in intrafollicular IGF-binding
      proteins -2, -4 and -5 levels. Proteolytic enzymes such as pregnancy-associated
      plasma protein-A (PAPP-A) degrade IGFBPs and increase bioavailability of IGF-I
      and -II during follicular development. The objective of this study was to
      determine the effect of IGF-I, IGF-II, insulin (INS), LH, FSH, estradiol (E2),
      leptin or cortisol on ovarian PAPP-A mRNA levels. Granulosa (GC) from small (SM)
      (1-5 mm) and large (LG) (8-22 mm) follicles as well as theca cells (TC) from LG
      follicles were collected from bovine ovaries and cultured for 48 h in medium
      containing 10% FCS and then treated with various hormones in serum-free medium
      for an additional 24 h. Cells were treated with various concentrations (3-500
      ng/ml) and combinations of IGF-I, IGF-II, FSH, LH, E2, INS, leptin and (or)
      cortisol for 24 h (Experiments 1-10). PAPP-A mRNA levels were measured using
      quantitative real-time RT-PCR. In SM-GC and LG-GC, none of the treatments
      significantly affected (P>0.10) PAPP-A mRNA abundance. In LG-TC, IGF-I, LH or
      cortisol did not affect (P>0.10) PAPP-A mRNA levels, whereas INS with or without
      LH decreased (P<0.05) PAPP-A mRNA. E2 alone decreased PAPP-A mRNA levels in LG
      TC, and E2 amplified the insulin-induced inhibition of PAPP-A mRNA abundance in
      LG-TC. We conclude that control of PAPP-A mRNA abundance in granulosa and theca
      cells differs, and that E2 may be part of an intraovarian negative feedback
      system which may reduce the bioavailable IGFs in the theca layer during growth
      and selection of follicles.

PMID- 16439094
TI  - 5-Year follow-up of sentinel node negative breast cancer patients.
AB  - AIM: To report the long-term results of sentinel node negative breast cancer
      patients treated without axillary lymph node dissection and the 5-year follow-up
      results of 149 patients. METHODS: The incidence of axillary-and local recurrences
      and second ipsilateral primary tumours was evaluated. The added value of annual
      ultrasound of the treated axilla, being part of the standard follow-up, was also
      evaluated. RESULTS: After a mean follow-up of 65 months (50-79) axillary
      recurrences were observed in four patients, local recurrences or ipsilateral
      second primary tumours were diagnosed in another seven patients. All axillary
      recurrences were diagnosed because of a palpable axillary mass; ultrasound in
      combination with fine needle aspiration cytology did not have an added value.
      CONCLUSION: It can be concluded that the incidence of axillary recurrences after
      negative SN is much lower than expected. There is no added value of US and FNAC
      of the axilla in the routine follow-up of SN negative patients.

PMID- 16439095
TI  - A truncated isoform of TMEFF2 encodes a secreted protein in prostate cancer
      cells.
AB  - The transmembrane protein TMEFF2, also known as tomoregulin or TENB2, has been
      proposed as a potential immunotherapeutic target for the treatment of prostate
      cancer. Much attention has focused on its limited tissue distribution, with
      strong expression seen only in the brain and the prostate. Here we describe the
      identification of a novel splice variant of TMEFF2 expressed both in the normal
      prostate and in prostate cancer. This variant encodes an isoform of TMEFF2 that
      is truncated after the first four coding exons, eliminating both the EGF-like and
      the transmembrane domains. Fusion of GFP to this isoform demonstrated that this
      variant transcript produces a truncated TMEFF2 protein (TMEFF2-S). In contrast to
      full-length TMEFF2-GFP, the truncated TMEFF2-S-GFP fusion protein was enriched in
      cytosolic granules, showed no staining at the plasma membrane, and was secreted
      into the medium of transfected cells grown in tissue culture. These results
      indicate that a truncated isoform of TMEFF2 is expressed from this locus. This
      secreted form of TMEFF2 may functionally interact with full-length TMEFF2, or its
      binding partners, and may also influence current immune-based treatment
      strategies.

PMID- 16439096
TI  - Effect of a PCB-based transformer oil on testicular steroidogenesis and
      xenobiotic-metabolizing enzymes.
AB  - Pyralene is a PCB-based transformer oil with a unique PCB congener profile when
      compared to other mixtures. We studied the influence of Pyralene on testicular
      steroidogenesis and the status of xenobiotic-metabolizing enzymes in the testis
      and liver of rats during oral exposure (10 and 50 mg/kg body weight, p.o. daily
      for 1 week) and a 3-week post-treatment recovery period. As expected, Pyralene
      induced a rapid and sustained increase in mRNA transcripts for CYP1A1 and CYP2B1
      in hepatocytes that was associated with a dramatic increase in ethoxyresorufin-O
      deethylase (EROD) and pentoxyresorufin-O-deethylase (PROD) activities. Testicular
      androgenesis and the conversion of progesterone to testosterone in testicular
      microsomes were bidirectionally affected. An increase in these parameters was
      observed 24h after the initial administration of Pyralene, followed by inhibition
      that lasted until the fourth post-treatment day. Expression PCR analysis revealed
      a significant decrease in 17beta-hydroxysteroid dehydrogenase (17betaHSD)
      transcript abundance at 48 h after Pyralene administration. In contrast,
      transcripts for several other steroidogenic enzymes and for testicular CYP1A1,
      CYP1B1, and CYP2B1 were unaffected under the same conditions. These results in
      the rat indicate that a sub-chronic exposure to Pyralene disrupted testicular
      steroidogenesis and suggest the mechanism may involve direct action on the
      regulation of specific steroidogenic enzymes such as 17betaHSD.

PMID- 16439097
TI  - The maternal combined supplementation of folic acid and Vitamin B(12) suppresses
      ethanol-induced developmental toxicity in mouse fetuses.
AB  - Maternal ethanol consumption during pregnancy can induce developmental defects in
      the fetus. The objective of this study was to assess whether combined
      supplementation of folic acid (FA) and Vitamin B(12) (VB(12)) in dams would
      suppress ethanol-induced developmental toxicity in CD-1 mice. Ethanol (5.0 g/kg)
      was given intragastrically from gestational day (GD) 6 to GD15. Vitamin
      supplementation groups were additionally given 60.0 mg/kg FA, 1.0 mg/kg VB(12),
      or 60.0 mg/kg FA+1.0 mg/kg VB(12) during GD1-16. The control group received
      distilled water only. Results of litter evaluation on GD18 showed that combined
      supplementation of FA and VB(12) ameliorated many of the adverse effects of
      ethanol. In contrast, the single vitamin supplementation groups showed little or
      no amelioration. These results suggest that combined supplementation of FA and
      VB(12) was more effective than each vitamin toward suppressing ethanol-induced
      developmental toxicity in CD-1 mice.

PMID- 16439098
TI  - Environmental contaminant levels and fecundability among non-smoking couples.
AB  - OBJECTIVE: To investigate the effects of low level maternal and paternal
      persistent contaminant exposures on fecundability among couples from the general
      population. METHODS: About 41 couples having their first pregnancy completed
      questionnaires and provided blood samples for analysis of metals, organochlorine
      pesticides, and polychorinated biphenyls. Associations of personal consumption
      and contaminant measures for mothers, fathers, and couples overall were analyzed
      through fecundability odds ratios (fOR, probability of pregnancy per month in
      more versus less exposed) in multivariable analyses. FINDINGS: Couples with
      higher reported caffeine consumption (couple consumption > or =111 drinks/month,
      fOR 0.25, 95% CI, 0.10, 0.63) and higher mercury concentrations in maternal blood
      (>1.2 microg/L or 0.24 ppm in hair, fOR 0.22, 95% CI, 0.07, 0.72) had lower
      fecundability, after adjustment for intercourse frequency. CONCLUSION: Reduced
      fecundability at levels below the mercury reference dose warrants further
      research and prudent reduction in persistent toxic substances exposure among
      women and men of reproductive age.

PMID- 16439099
TI  - Differential progression of neonatal diethylstilbestrol-induced disruption of the
      hamster testis and seminal vesicle.
AB  - The synthetic estrogen diethylstilbestrol (DES) is now recognized as the
      prototypical endocrine disruptor. Using a hamster experimental system, we
      performed a detailed temporal assessment of how neonatal DES-induced disruption
      progresses in the testis compared to the seminal vesicle. Both morphological and
      Western blot analyses confirmed that neonatal DES exposure alters androgen
      responsiveness in the male hamster reproductive tract. We also determined that
      the disruption phenomenon in the male hamster is manifest much earlier in the
      seminal vesicle than in the testis and that testis disruption often occurs
      differently between the pair of organs in a given animal. In the neonatally DES
      exposed seminal vesicle, histopathological effects included: (1) general atrophy,
      (2) lack of exocrine products, (3) epithelial dysplasia, (4) altered organization
      of stromal cells and extracellular matrix, and (5) striking infiltration with
      polymorphonuclear leukocytes. Also, the morphological disruption phenomenon in
      the seminal vesicle was accompanied by a range of up-regulation and down
      regulation responses in the whole organ levels of various proteins.

PMID- 16439100
TI  - Reconstruction of the mandible after ablative surgery for the treatment of
      aggressive, benign odontogenic tumours in Tanzania: a preliminary study.
AB  - This study presents results on 11 patients suffering from ameloblastoma who had
      ablative surgery followed by reconstruction of the mandible in a single operative
      procedure in Tanzania. The procedure included the use of autogenous particulate
      bone from the anterior or posterior iliac crest. In 6 of the patients, the tumour
      was removed from the cortical scaffold, which was then irradiated with 50 Gy.
      Perforations were made on the scaffold and it was then placed back to fit the
      defect and was held in place by custom-made titanium plates, fixed on both ends
      with screws. The particulate bone chips were mixed with autogenous platelet rich
      plasma (PRP) and Tissue Col. In 5 of the patients, the cortical scaffold was not
      used but rather a mixture of bone and PRP was packed into the defect under the
      titanium plates. Four patients had some complications varying from fracture of
      the scaffolds to infection. None from the group reconstructed without scaffolds
      suffered any complications. A quality of life (QOL) assessment of the 7
      successful cases showed that these patients were satisfied and had a good QOL.
      These results imply that this immediate means of reconstruction is feasible and
      thus, offers a big advantage to the patients.

PMID- 16439101
TI  - Regulation of toxin and bacteriocin synthesis in Clostridium species by a new
      subgroup of RNA polymerase sigma-factors.
AB  - Many Clostridium species are pathogenic for humans and animals, and most of the
      resulting diseases, such as tetanus, botulism, gas gangrene and pseudomembranous
      colitis, are due to the production of potent extracellular toxins. The
      biochemical mechanisms of action of Clostridium toxins have been extensively
      studied in the past ten years. However, detailed information about the regulation
      of toxin gene expression has only recently emerged. TcdR, BotR, TetR and UviA are
      now known to be related alternative RNA polymerase sigma factors that drive
      transcription of toxin A and toxin B genes in C. difficile, the neurotoxin genes
      in C. botulinum and C. tetani, and a bacteriocin gene in C. perfringens. Although
      the Clostridium sigma factors have some similarity to members of the ECF sigma
      factor group, they differ sufficiently in structure and function so that they
      have been assigned to a new group within the sigma(70)-family.

PMID- 16439102
TI  - Suitability of different photosynthetic organisms for an extraterrestrial
      biological life support system.
AB  - In the present era of intensive space and planetary research, efficient life
      support systems (LSSs) are needed to maintain suitable living conditions when
      humans move into space, i.e. away from the Earth's atmosphere. Thus far, such
      suitable conditions on various space flights and on the space stations (Mir and
      the International Space Station) have been maintained solely via physical and
      chemical means (transport of O2, H2O and food from the Earth, cleaning and
      recycling of air and water). However, for long-duration missions to distant
      destinations, such as exploratory missions to Mars, biological life support
      systems (BLSSs) may be needed to convert local CO2 and H2O to O2, and to food. As
      on earth, this conversion process would need to be based on photosynthesis. Use
      of higher plants and microalgae as BLSS organisms has been intensively studied.
      Here we review the growth requirements of these two types of photosynthetic
      organisms, with particular attention to their suitability for use in harsh
      Martian conditions, i.e. low temperatures, low atmospheric pressure, high CO2
      concentration, high UV radiation and dryness.

PMID- 16439103
TI  - Alterations in intestinal fatty acid metabolism in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) constitutes a severe intestinal disorder in
      developed countries with increasing incidence worldwide. Upcoming evidence
      indicates an important role of intestinal epithelial barrier function in the
      development of IBD. Fatty acids exert nutritional and protective effects on
      enterocytes, serve as activators of transcription and constitute precursors of
      inflammatory mediators. The aim of this study was to investigate differential
      regulation of genes involved in fatty acid uptake and endogenous fatty acid
      biosynthesis in IBD. Mucosal biopsy specimens from non-affected regions of the
      intestine were subjected to DNA microarray analysis. Gene array analysis revealed
      a variety of genes involved in fatty acid uptake and synthesis to be
      differentially expressed in ileum and colon of selected IBD patients. To verify
      these results, real-time RT-PCR was performed for selected regulated candidate
      genes in larger IBD sample numbers. In single biopsy analysis long chain acyl-CoA
      synthetase (ACSL) 1 and 4 were upregulated in IBD (P<0.05), while a significant
      decrease in fatty acid synthase expression was found in ileum and colon of
      ulcerative colitis patients (P<0.001). Expression of the transcription factor
      liver X receptor (LXR) which was previously shown to induce fatty acid synthase
      gene expression was not altered on mRNA level in IBD. However, in cell culture
      experiments using the human intestinal cell line LS174T induction of fatty acid
      synthase by the LXR ligand T0901317 was inhibited by TNFalpha. Moreover, these
      experiments indicated a decrease of LXR protein levels by TNFalpha treatment.
      These data suggest that the decrease of fatty acid synthase expression in
      ulcerative colitis patients could be at least partially due to a loss of LXR
      expression and function in the presence of pro-inflammatory cytokines. Observed
      alterations in expression of genes of fatty acid metabolism may contribute to the
      pathophysiology of ulcerative colitis.

PMID- 16439104
TI  - Influence of dairy manure addition on the biological and thermal kinetics of
      composting of greenhouse tomato plant residues.
AB  - A laboratory-scale bioreactor was used to investigate the influence of dairy
      manure addition (as an inoculum and a carbon source) on the biological and
      thermal kinetics of the composting process of tomato plant residues-wood shavings
      mixture. Urea was added (as a nitrogen source) to correct the initial C:N ratio
      to 30:1 and the initial moisture content was also adjusted to 60%. The result of
      this study indicated that manure addition to the tomato residues-wood shavings
      mixture is a good source of macro and micronutrients required for supporting the
      composting microorganisms. Manure addition increased the rate of temperature
      increase and the duration of maximum temperature and reduced the lag and the peak
      time, all of which resulted in a significant reduction in the retention time.
      However, thermophilic temperature (> or = 40 degrees Celsius) was only achieved
      with 30%, 40% and 50% manure addition for 3, 7 and 9h. Total carbon reductions
      were in the range of 9.4-10.8% and TKN reductions were in the range of 3.4-6.0%.
      Neither the nitrogen nor the moisture content were limiting factors as the C:N
      ratio remained in the range of 26:1 to 28:1 and the moisture content remained
      within the optimum range of 58-61%. The maximum temperature of each mixture
      correlated with the reduction of total carbon, but carbon availability was a
      limiting factor in these experiments. In order to attain and sustain a
      thermophilic phase during the composting process, the addition of a readily
      available carbon source to the tomato should be investigated and carbon type
      (carbohydrates, proteins and fats) should be taken into account.

PMID- 16439105
TI  - Flow analysis of metals in a municipal solid waste management system.
AB  - This study aimed to identify the metal flow in a municipal solid waste (MSW)
      management system. Outputs of a resource recovery facility, refuse derived fuel
      (RDF) production facility, carbonization facility, plastics liquefaction
      facility, composting facility, and bio-gasification facility were analyzed for
      metal content and leaching concentration. In terms of metal content, bulky and
      incombustible waste had the highest values. Char from a carbonization facility,
      which treats household waste, had a higher metal content than MSW incinerator
      bottom ash. A leaching test revealed that Cd and Pb in char and Pb in RDF
      production residue exceeded the Japanese regulatory criteria for landfilling, so
      special attention should be paid to final disposal of these substances. By
      multiplying metal content and the generation rate of outputs, the metal content
      of input waste to each facility was estimated. For most metals except Cr, the
      total contribution ratio of paper/textile/plastics, bulky waste, and
      incombustible waste was over 80%. Approximately 30% of Cr originated from plastic
      packaging. Finally, several MSW management scenarios showed that most metals are
      transferred to landfills and the leaching potential of metals to the environment
      is quite small.

PMID- 16439106
TI  - Characterization and optimization of two methods in the immobilization of 12
      bioluminescent strains.
AB  - Twelve recombinant bioluminescent bacteria have been immobilized within the wells
      of a 96-well plate using two different matrices--agar and sol-gel. All 12 strains
      were immobilized within individual wells of the plates and the sensitivity of the
      strains and the stability of the responses were determined for select chemicals.
      Each strain was exposed to seven well-characterized chemicals over a wide range
      of concentrations to demonstrate their individual selectivity for specific
      toxicants. Although the sensitivity of the immobilized cells was generally lower
      than cultures grown in liquid media, they were comparable. For example, strain
      DPD1710, which responds to DNA damage was able to detect mitomycin C, a
      genotoxin, at a minimum concentration of 0.6 ppb. When immobilized, the lower
      limit of detection was between 1 and 10 ppb. Finally, using compounds that are
      known to elicit a response from each of the strains, the stability of the
      bioluminescent responses were measured over an extended period of 4 weeks.
      Although the activity of several strains decreased over time, the majority of the
      strains used in both immobilized systems were still responsive.

PMID- 16439107
TI  - An amplified mass piezoelectric immunosensor for Schistosoma japonicum.
AB  - An ultrasensitive piezoelectric immunosensor using an amplification path based on
      an insoluble biocatalyzed precipitation product has proposed for Schistosoma
      japonicum. A mercapto Schistosoma japonicum antigen was self-assembled onto the
      quartz crystal surface via an Au nanoparticle mediator monolayer to sense the
      Schistosoma japonicum antibody (SjAb). And the horseradish peroxidase labeled
      protein A conjugate which was bounded to the SjAb by a "sandwich" format was used
      as a biocatalyst for the oxidative precipitation of 4-chloro-1-naphthol by
      H(2)O(2) to yield the insoluble product benzo-4-chlorohexadienone, resulting in
      an amplified mass sensing of antigen-antibody interaction. The amount of the
      precipitate accumulated on the quartz crystal is controlled by the antibody
      concentration. The SjAb can be linearly determined in the range of 10-200 ngml(
      1) and the detection limit reaches as low as 5 ngml(-1).

PMID- 16439108
TI  - Micro analysis system for pH and protease activities with an integrated sample
      injection mechanism.
AB  - A micro analysis system for the electrochemical determination of the activity of
      protease along with pH sensing was fabricated aiming for its use in telemetric
      micro analysis systems targeting the testing of the stomach and intestines. The
      system consisted of a pH-sensing site and two protease assay sites formed in
      polydimethylsiloxane (PDMS) micro flow channels. To introduce sample solutions,
      valves were formed with gold electrodes in the inlets, which functioned on the
      basis of electrowetting. An external sample solution could be introduced into the
      sensing sites by switching on the valves at appropriate times. In the pH-sensing
      site, a pH-indicator electrode changed its electrode potential immediately after
      a sample solution reached an internal liquid-junction reference electrode. The
      slope of the calibration plot was -74.5 mVpH(-1). Bovine serum albumin (BSA) was
      used as the substrate for the enzyme and was spotted on the wall of the flow
      channel that faced the pH-indicator electrode of the protease assay sites. The
      release of protons accompanying the hydrolysis of BSA by the enzyme was detected
      using the pH-indicator electrode. When trypsin was contained in the sample
      solution as a test enzyme, a distinct decrease in pH, which was dependent on the
      trypsin activity, was observed, indicating that enzymatic hydrolysis was
      proceeding. The initial rate of potential change varied in proportion to the
      activity in a range between 1.0 and 51.7 Uml(-1). The integration of the
      microfluidic and sensing functions provides significant advantages for the use of
      this system as an isolated telemetric micro system that might operate with small
      batteries.

PMID- 16439110
TI  - Structure-specific DNA nucleases: structural basis for 3D-scissors.
AB  - Structure-specific DNA nucleases play important roles in various DNA transactions
      such as DNA replication, repair and recombination. These enzymes recognize loops
      and branched DNA structures. Recent structural studies have provided detailed
      insights into the functions of these enzymes. Structures of Holliday junction
      resolvase revealed that nucleases are broadly diverged in the way in which they
      fold, however, are required to form homodimers with large basic patches of
      protein surfaces, which are complementary to DNA tertiary structures. Many
      nucleases maintain structure-specific recognition modes, which involve particular
      domain arrangements through conformal changes of flexible loops or have a
      separate DNA binding domain. Nucleases, such as FEN-1 and archaeal XPF, are bound
      to proliferating cell nuclear antigen through a common motif, and thereby
      actualize their inherent activities.

PMID- 16439111
TI  - Endothelin-3 production by human rhabdomyosarcoma: a possible new marker with a
      paracrine role.
AB  - Several autocrine and paracrine growth factor circuits have been found in human
      rhabdomyosarcoma cells. In this study we show that endothelin-3 (ET-3), a
      vasoactive peptide, is produced by human rhabdomyosarcoma cell lines, whereas it
      is not expressed by human sarcoma cell lines of non-muscle origin. We did not
      find evidence of a significant autocrine loop; nevertheless ET-3 produced by
      rhabdomyosarcoma cells can act as a paracrine factor, since it promotes migration
      of endothelial cells. Moreover ET-3 is present in plasma of mice bearing
      xenografts of human rhabdomyosarcoma cells, and may be potential new marker of
      the human rhabdomyosarcoma to be studied further.

PMID- 16439112
TI  - Chronomodulated chemotherapy for colorectal cancer: failing the test of time?

PMID- 16439113
TI  - Identification of covalent attachment site of antiestrogenic estradiol 11 beta
      derivatives on human estrogen receptor alpha ligand-binding domain.
AB  - Affinity labeling of human estrogen receptor alpha (ERalpha) by high affinity and
      antiestrogenic estradiol (E(2)) 11 beta-derivatives, 11 beta
      bromoacetamidoethoxyphenylE(2) (11BAEOPE(2)) and 11 beta
      bromoacetamidopentoxyphenylE(2) (11BAPOPE(2)) was studied using glutathione-S
      transferase (GST) fused to the ligand-binding domain (LBD) of human ERalpha. To
      identify and quantify the electrophile covalent attachment sites on LBD,
      [(14)C]11BAEOPE(2)- and [(14)C]11BAPOPE(2)-alkylated LBD were separated from GST,
      purified, and then trypsinized. HPLC of LBD tryptic fragments afforded one and
      two radioactive peaks (the ratio of the two latter peaks was 84/16) in the
      chromatograms related to LBD alkylated by 11BAEOPE(2) and 11BAPOPE(2),
      respectively. Mass spectrometry (MS) analyses of the fractions related to the
      single peak and to the major one of the two peaks showed signals which accurately
      matched the mass of electrophile-alkylated Cys(530)Lys(531) LBD tryptic peptide,
      whereas no signal compatible with an alkylated form of an LBD tryptic peptide was
      detected in the MS analysis of the minor peak-related fractions. MS/MS analysis
      of alkylated CysLys dipeptide revealed the presence of fragments that
      unambiguously designated the Cys S as the covalent attachment site of the
      electrophiles. We attempted to interpret the biochemical data by molecular
      modeling using various crystallographic structures of human LBD-ligand complexes.
      In agreement with the endocrine properties of electrophiles, labeling at Cys(530)
      could be accounted for by a LBD structure derived from LBD bound to 4
      hydroxytamoxifen, a triphenylethylene antiestrogen. The common attachment to
      Cys(530) of estrogenic E(2) 17 alpha-derivatives [H. Mattras, S. Aliau, E. Demey,
      J. Poncet, J.L. Borgna, Mass spectrometry identification of covalent attachment
      sites of two related estrogenic ligands on human estrogen receptor alpha, J.
      Steroid Biochem. Mol. Biol. 98 (4-5), in press] and antiestrogenic E(2) 11 beta
      derivatives suggests that the LBD portion encompassing this amino acid possesses
      a marked plasticity.

PMID- 16439114
TI  - A method for controlling hydrogen sulfide in water by adding solid phase oxygen.
AB  - This work evaluates the addition of solid phase oxygen, a magnesium peroxide
      (MgO(2)) formulation manufactured by Regenesis (oxygen-releasing compounds, ORC),
      to inhibit the production of hydrogen sulfide (H(2)S) in an SRB-enriched
      environment. The initial rate of release of oxygen by the ORC was determined over
      a short period by adding sodium sulfite (Na(2)SO(3)), which was a novel approach
      developed for this study. The ability of ORCs to control H(2)S by releasing
      oxygen was evaluated in a bench-scale column containing cultured sulfate reducing
      bacteria (SRB). After a series of batch tests, 0.4% ORC was found to be able to
      inhibit the formation of H(2)S for more than 40 days. In comparison, the
      concentration of H(2)S dropped from 20 mg S/L to 0.05 mg S/L immediately after
      0.1% hydrogen peroxide (H(2)O(2)) was added, but began to recover just four days
      later. Thus, H(2)O(2) does not seem to be able to inhibit the production of
      sulfide for an extended period of time. By providing long-term inhibition of the
      SRB population, ORC provides a good alternative means of controlling the
      production of H(2)S in water.

PMID- 16439115
TI  - Beta'-hydroxy-alpha,beta-unsaturated ketones: a new pharmacophore for the design
      of anticancer drugs.
AB  - A series of beta'-hydroxy-alpha,beta-unsaturated ketones were prepared by means
      of an iron(III) catalyzed domino process. The in vitro antiproliferative
      activities were examined in the human solid tumor cell lines A2780, SW1573, and
      WiDr. The results showed that beta'-hydroxy-alpha,beta-unsaturated ketones were
      more potent than alpha,beta-unsaturated ketones. The best activity profiles were
      obtained for the derivatives bearing cyclic or branched substituents on the side
      chains.

PMID- 16439116
TI  - Synthesis and activity of small molecule GPR40 agonists.
AB  - The first report on the identification and structure-activity relationships of a
      novel series of GPR40 agonists based on a 3-(4-{[N-alkyl]amino}phenyl)propanoic
      acid template is described. Structural modifications to the original screening
      hit yielded compounds with a 100-fold increase in potency at the human GPR40
      receptor and pEC(50)s in the low nanomolar range. The carboxylic acid moiety is
      not critical for activity but typically elicits an agonistic response higher than
      those observed with carboxamide replacements. These compounds may prove useful in
      unraveling the therapeutic potential of this receptor for the treatment of Type 2
      diabetes.

PMID- 16439117
TI  - Azolylchromans as a novel scaffold for anticonvulsant activity.
AB  - A series of azolylchroman derivatives were prepared as conformationally
      constrained analogs of (arylalkyl)azole anticonvulsants. The anticonvulsant
      activities of the compounds were evaluated by determining seizure latency and
      protective effect against pentylenetetrazole (PTZ)-induced lethal convulsions in
      mice at a dose of 5mg/kg. Among these compounds, 7-chloro-3-(1H-imidazol-1
      yl)chroman-4-one and 3-(1H-1,2,4-triazol-1-yl)chroman-4-one exhibited significant
      action in delaying seizures as well as effective protection against PTZ-induced
      seizures and deaths.

PMID- 16439118
TI  - The water-soluble fullerene derivative "Radical Sponge" exerts cytoprotective
      action against UVA irradiation but not visible-light-catalyzed cytotoxicity in
      human skin keratinocytes.
AB  - Fullerene was entrapped in polyvinylpyrrolidone of 60-80 kDa at a molar ratio
      range of 0.42-0.67:1, resulting in a water-soluble derivative with a mean
      particle diameter of about 688 nm, named "Radical Sponge" because of its ROS
      scavenging ability as previously demonstrated, and examined in the present study
      for its photo-biological actions toward human skin keratinocytes HaCaT. The
      keratinocytes were repeatedly irradiated with a visible light of wavelengths of
      400-2000 nm (approximately 19,800 lux) in the presence or absence of Radical
      Sponge of 25-75 microM and did not exhibit any photo-cytotoxicity due to
      coexistent Radical Sponge as compared with the sham-irradiation control. Radical
      Sponge exerted a more marked cytoprotection at doses of 10-40 microM against UVA
      irradiation of 30 J/cm(2) when it was pre-irradiationally administered and rinsed
      out immediately before the irradiation, than when administered only during or
      after the irradiation, indicating the preventive rather than therapeutic or ray
      sheltering effect of Radical Sponge on UVA injuries. Cytoprotection by Radical
      Sponge against UVA was achieved at the advisable range doses of 10-40 microM in
      contrast to no effect of polyvinylpyrrolidone alone; its dose-dependency was
      advantageous over that of VC-IP, a tetra-alkyl-esterized provitamin C, which
      became less cytoprotective above 20 microM. Thus, Radical Sponge is expected as
      an anti-UVA-preventive agent without visible-light-catalyzed cytotoxicity toward
      human skin keratinocytes.

PMID- 16439119
TI  - Semi-synthetic preparation of the rare, cytotoxic, deep-sea sourced sponge
      metabolites discorhabdins P and U.
AB  - Semi-synthetic routes to the enzyme inhibitory and potently anti-proliferative
      marine natural products discorhabdins P and U were developed by one-step
      methylation reactions of discorhabdins C and B, respectively. Two novel semi
      synthetic derivatives of discorhabdin U were also prepared, one of which (6)
      exhibited significant anti-proliferative activity.

PMID- 16439121
TI  - First dual M3 antagonists-PDE4 inhibitors: synthesis and SAR of 4,6
      diaminopyrimidine derivatives.
AB  - SAR around 4,6-diaminopyrimidine derivatives allowed the discovery of the first
      potent dual M(3) antagonists and PDE4 inhibitors. Various chemical modulations
      around that scaffold led to the discovery of ucb-101333-3 which is characterized
      by the most interesting profile on both targets.

PMID- 16439120
TI  - Arylmethoxypyridines as novel, potent and orally active mGlu5 receptor
      antagonists.
AB  - Optimisation of affinity, chemical stability, metabolic stability and solubility
      led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with
      high affinity for the allosteric MPEP binding site, improved microsomal metabolic
      stability and anxiolytic-like activity in vivo as assessed by the Vogel conflict
      drinking test.

PMID- 16439122
TI  - Kinesin spindle protein (KSP) inhibitors. Part 3: synthesis and evaluation of
      phenolic 2,4-diaryl-2,5-dihydropyrroles with reduced hERG binding and employment
      of a phosphate prodrug strategy for aqueous solubility.
AB  - 2,4-Diaryl-2,5-dihydropyrroles have been discovered to be novel, potent and water
      soluble inhibitors of KSP, an emerging therapeutic target for the treatment of
      cancer. A potential concern for these basic KSP inhibitors (1 and 2) was hERG
      binding that can be minimized by incorporation of a potency-enhancing C2 phenol
      combined with neutral N1 side chains. Aqueous solubility was restored to these,
      and other, non-basic inhibitors, through a phosphate prodrug strategy.

PMID- 16439123
TI  - Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and
      characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic
      kinesin KSP.
AB  - The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is
      described. Introduction of basic amide and urea moieties to the dihydropyrrole
      nucleus enhanced potency and aqueous solubility, simultaneously, and provided
      compounds that caused mitotic arrest of A2780 human ovarian carcinoma cells with
      EC(50)s<10nM. Ancillary hERG activity was evaluated for this series of
      inhibitors.

PMID- 16439125
TI  - Dda helicase unwinds a DNA-PNA chimeric substrate: evidence for an inchworm
      mechanism.
AB  - Helicases are ubiquitous enzymes involved in all aspects of DNA metabolism
      including replication, repair, recombination, and transcription. The mechanism of
      the bacteriophage T4 Dda helicase was investigated by preparing a DNA-PNA
      chimeric substrate. Surprisingly, Dda was able to unwind a substrate containing
      12 PNA moieties in the loading strand of the enzyme. We suggest a mechanism
      whereby the Dda helicase contains two distinct DNA binding domains which allow an
      inchworm mechanism for translocation. A single step of the enzyme is sufficient
      to unwind the DNA-PNA chimera because several base pairs melt spontaneously due
      to thermal fraying. Hence, Dda helicase can unwind the substrate without actually
      translocating along the PNA.

PMID- 16439124
TI  - Beta-diketo acids with purine nucleobase scaffolds: novel, selective inhibitors
      of the strand transfer step of HIV integrase.
AB  - The HIV pol gene encodes three viral enzymes that are required for its
      replication. While drug discovery involving the viral targets, reverse
      transcriptase and protease, has resulted in useful therapeutic agents, such
      efforts on HIV integrase have not produced a single FDA-approved drug. In the
      work focused on the discovery of inhibitors of HIV integrase, we have synthesized
      new beta-diketo acids with purine nucleobase scaffolds that are potent inhibitors
      of the strand transfer steps of wild-type HIV-1 integrase.

PMID- 16439126
TI  - Synthesis of alpha-substituted fosmidomycin analogues as highly potent Plasmodium
      falciparum growth inhibitors.
AB  - In view of the promising antimalarial activity of fosmidomycin or its N-acetyl
      homologue FR900098, the objective of this work was to investigate the influence
      of aromatic substituents in the alpha-position of the phosphonate moiety. The
      envisaged analogues were prepared using a linear route involving a 3-aryl-3
      phosphoryl propanal intermediate. The activities of all compounds were evaluated
      on Eschericia coli 1-deoxy-d-xylulose 5-phosphate reductoisomerase and against
      two Plasmodium falciparum strains. Compared with fosmidomycin, several analogues
      displayed enhanced activity towards the P. falciparum strains. Compound 1e with a
      3,4-dichlorophenyl substitution in the alpha-position of fosmidomycin emerged as
      the most potent analogue of this series. It is approximately three times more
      potent in inhibiting the growth of P. falciparum than FR900098, the most potent
      representative of this class reported so far.

PMID- 16439127
TI  - Synthesis and SAR of highly potent and selective dopamine D3-receptor
      antagonists: variations on the 1H-pyrimidin-2-one theme.
AB  - In our efforts to further pursue one of the most selective dopamine D(3)-receptor
      antagonists reported to date, we now describe the synthesis and SAR of novel and
      highly selective dopamine D(3) antagonists based on a 1H-pyridin-2-one or on a
      urea scaffold. The most potent compounds exhibited K(i) values toward the D(3)
      receptor in the nano- to subnanomolar range and high selectivity versus the
      related D(2) dopamine receptor. Thus, 1H-pyridin-2-one 7b displays oral
      bioavailability (F=37%) as well as brain penetration (brain plasma ratio 3.7) in
      rat. Within the urea series, an excellent D(3) versus D(2) selectivity (>100
      fold) could be achieved by removal of one NH group (compound 6), although
      bioavailability (rat) was suboptimal (F<10%). These data significantly enhance
      our understanding of the D(3) pharmacophore and are expected to lead to novel
      approaches for the treatment of schizophrenia.

PMID- 16439128
TI  - Synthesis and stability of two indomethacin prodrugs.
AB  - The purpose of this study was to synthesize and study the in vitro enzymatic and
      non-enzymatic hydrolysis of indomethacin-TEG ester and amide prodrugs. It was
      found that the ester conjugate 10 was comparatively stable between pH 3 and 6
      (half-life>90h), with a half-life equal to 5.2h in 80% buffered plasma. In
      contrast, the amide conjugate 12 appeared to be stable over the entire pH range
      studied with the only observed degradation being cleavage of the indolic N-4
      chlorobenzoyl moiety.

PMID- 16439129
TI  - Partial irradiation of the breast: Old challenges, new solutions.
AB  - Breast-conserving treatment, characteristically consisting of surgical removal of
      the tumor and post-operative whole breast irradiation, is nowadays considered as
      the standard therapeutic approach for most women with stage I/II, invasive breast
      cancer. Recently, a number of institutions started investigating the feasibility
      and safety of novel approaches in radiotherapy, modulating concomitantly
      treatment time and irradiation volume. Whilst this strategy is still under
      investigation, recent clinical studies on accelerated partial breast irradiation
      with intra-operative radiotherapy or high conformality irradiation strongly
      suggest that the way patients with early breast cancer are irradiated should be
      revisited.

PMID- 16439130
TI  - Methodology for determining the sensitivity of swing leg toe clearance and leg
      length to swing leg joint angles during gait.
AB  - During the swing phase of gait, the effective length of the leg-distance from the
      hip joint center to the toe-must be made shorter than the distance from the hip
      to the floor to avoid toe-stubbing or tripping while walking. Critical toe
      clearance occurs approximately halfway through swing phase when the distance
      between the toe and the floor reaches a local minimum. Analytical techniques
      derived in this study were used to evaluate: (1) the sensitivity of toe clearance
      to the swing leg hip, knee, and ankle joint angles; and (2) the sensitivity of
      the hip-toe distance to the swing leg knee and ankle joint angles. The toe
      clearance, hip-toe distance, toe clearance sensitivity (TCS), and hip-toe
      distance sensitivity (HTDS) were calculated for each frame of data during the
      swing phase of 10 able-bodied subjects. A minimum toe clearance of 1.9+/-0.5cm
      occurred at about 51% of the swing phase during able-bodied gait. At that
      particular time, the toe clearance was found to be most sensitive to the angle of
      the ankle (17.1cm/rad), then the hip (9.5cm/rad), and lastly the knee
      (2.5cm/rad). The hip-toe distance was found to be about twice as sensitive to the
      angle of the ankle (-15.3cm/rad) than to that of the knee (-7.6cm/rad) at the
      time of critical toe clearance. The methodology developed here and the baseline
      information calculated for able-bodied subjects could be used to evaluate the
      effects that different gait pathologies have on swing-phase toe clearance and hip
      toe distance.

PMID- 16439131
TI  - Somatosensory disinhibition and frontal alien hand signs following medial frontal
      damage.
AB  - We report augmentation of somatosensory evoked potentials (SEP) in a patient with
      frontal alien hand signs after left medial frontal lobe damage. The SEP
      components occurring later than 30 msec post stimuli were enhanced over the
      parietal and frontal scalp sites of the lesioned hemisphere. This finding
      suggests that deficits in inhibitory control of somatosensory processing in
      parietal and frontal lobes contributes in some way to frontal alien hand signs.

PMID- 16439132
TI  - Multimodality treatment of trigeminal neuralgia: impact of radiosurgery and high
      resolution magnetic resonance imaging.
AB  - This study was conducted to evaluate the two main surgical modalities,
      microvascular decompression (MVD) and gamma-knife radiosurgery (GK), the
      treatment of trigeminal neuralgia (TN) and outline for an algorithm for the
      selection of these procedures. The authors have identified distinct differences
      in the two treatment groups and formulated a scale that predicts the outcome and
      satisfaction of patients who underwent the procedures. This series included 34 TN
      patients treated in 2000 and 2001 with MVD (19) and GK (15). Patients with TN
      associated with tumor or multiple sclerosis were excluded. Each patient's age,
      past medical history, clinical features of pain or pre-operative pain grade,
      duration of TN, medications, and prior surgical procedures were recorded. Long
      term results were assessed by a structured interview by telephone. Clinical
      outcome was classified as excellent (complete relief without medications and
      numbness), good (complete relief without medications), fair (> 50% relief or with
      substantial numbness and weakness), or poor (< 50% relief or treatment failure).
      Patient self-rated satisfaction score was rated on a scale of 1 (unsatisfied) to
      10 (completely satisfied). Statistical analysis was performed by paired t-tests
      and anova with post-hoc analysis by the Tukey-Kramer method. The median follow-up
      was 17 months (18 months for MVD and 16 months for GK). The average age of MVD
      patients was 61 years compared to 74 years for GK patients (p = 0.0005). In both
      groups there was a female majority (68% for MVD and 60% for GK). The latency
      between first symptom of TN and treatment procedure was 3.0 years for MVD and 3.9
      years for GK (p > 0.05). There was no significant difference in pain grade
      between the two groups. The average TN complexity grade was significantly
      different between the two groups (3.0 for MVD and 5.8 for GK) (p < 0.001).
      Average response to procedure for MVD was 3.4 (good) and 2.4 (fair) for GK (p =
      0.017). The satisfaction outcome for MVD was 8.7 compared to 6.4 for GK (p =
      0.02). There was a significant correlation (r = -0.818, p < 0.001) between TN
      complexity grade and response. Additionally, a significant correlation between TN
      complexity grade and patient satisfaction was found (r = -0.763, p < 0.0001). The
      data here support the treatment algorithm employed by the senior author (JFA) of
      this study. The TN complexity grade accurately correlates with the patient's
      response and satisfaction to the surgical procedure. This complexity grade may be
      useful for patient counseling when choosing between treatment options.

PMID- 16439133
TI  - Cerebral amyloid angiopathy presenting with vasculitic pathology.
AB  - We present an elderly patient with an unusual extensive multifocal central
      nervous system mass lesion, with dramatic imaging changes but only minor
      disturbance of cerebral function. Cerebral biopsy revealed an unexpected finding
      of severe cerebral amyloid angiopathy with secondary florid vasculitic
      appearances, which is a very rare but recognised association. Immunosuppression
      has produced significant sustained clinical and radiological remission.

PMID- 16439134
TI  - Spin trapping of C- and O-centered radicals with methyl-, ethyl-, pentyl-, and
      phenyl-substituted EMPO derivatives.
AB  - In order to develop spin traps with an optimal ratio between hydrophilic and
      lipophilic properties, low toxicity, and high stability of spin adducts
      (especially with superoxide radicals), several EMPO-derived spin traps have
      recently been synthesized forming more stable superoxide adducts (t(1/2) > 20
      min) than DMPO or DEPMPO. In this study, ESR-, 1H-, and 13C-NMR data of several
      phenyl- or n-pentyl-substituted EMPO derivatives are presented with full signal
      assignment. Methyl groups at position 3 or 4 stabilized the superoxide adducts
      considerably. Spin adducts from other oxygen- and carbon-centered radicals (e.g.,
      derived from methanol or linoleic acid hydroperoxide) are also described.

PMID- 16439135
TI  - Chlamydocin analogs bearing carbonyl group as possible ligand toward zinc atom in
      histone deacetylases.
AB  - A series of chlamydocin analogs with various carbonyl functionalities were
      designed and synthesized as histone deacetylase (HDAC) inhibitors. Chlamydocin is
      a cyclic tetrapeptide containing an epoxyketone surrogate in the side chain which
      makes it irreversible inhibitor of HDACs, whereas apicidins are a class of cyclic
      tetrapeptides that contain an ethylketone moiety as zinc ligand. We replaced the
      epoxyketone moiety of chlamydocin with several ketones and aldehyde to synthesize
      potent reversible and selective HDAC inhibitors. The inhibitory activity of the
      cyclic tetrapeptides against histone deacetylase enzymes were evaluated and the
      result showed most of them are potent inhibitors. Some of them have remarkable
      selectivity among the HDACs.

PMID- 16439137
TI  - Heterocyclic rimantadine analogues with antiviral activity.
AB  - 2-(1-Adamantyl)-2-methyl-pyrrolidines 3 and 4, 2-(1-adamantyl)-2-methyl
      azetidines 5 and 6, and 2-(1-adamantyl)-2-methyl-aziridines 7 and 8 were
      synthesized and tested for their antiviral activity against influenza A. Parent
      molecules 3, 5, and 7 contain the alpha-methyl-1-adamantan-methanamine 2
      pharmacophoric moiety (rimantadine). The ring size effect on anti-influenza A
      activity was investigated. Pyrrolidine 3 was the most potent anti-influenza virus
      A compound, 9-fold more potent than rimantadine 2, 27-fold more potent than
      amantadine 1, and 22-fold more potent than ribavirin. Azetidines 5 and 6 were
      both markedly active against influenza A H2N2 virus, 10- to 20-fold more potent
      than amantadine. Aziridine 7 was almost devoid of any activity against H2N2 virus
      but exhibited borderline activity against H3N2 influenza A strain. Thus, it
      appears that changing the five-, to four- to a three-membered ring results in a
      drop of activity against influenza A virus.

PMID- 16439136
TI  - Structural and functional characterization of human microsomal prostaglandin E
      synthase-1 by computational modeling and site-directed mutagenesis.
AB  - Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) has recently been recognized
      as a novel, promising drug target for inflammation-related diseases. Functional
      and pathological studies on this enzyme further stimulate to understand its
      structure and the structure-function relationships. Using an approach of the
      combined structure prediction, molecular docking, site-directed mutagenesis, and
      enzymatic activity assay, we have developed the first three-dimensional (3D)
      model of the substrate-binding domain (SBD) of mPGES-1 and its binding with
      substrates prostaglandin H2 (PGH2) and glutathione (GSH). In light of the 3D
      model, key amino acid residues have been identified for the substrate binding and
      the obtained experimental activity data have confirmed the computationally
      determined substrate-enzyme binding mode. Both the computational and experimental
      results show that Y130 plays a vital role in the binding with PGH2 and, probably,
      in the catalytic reaction process. R110 and T114 interact intensively with the
      carboxyl tail of PGH2, whereas Q36 and Q134 only enhance the PGH2-binding
      affinity. The modeled binding structure indicates that substrate PGH2 interacts
      with GSH through hydrogen binding between the peroxy group of PGH2 and the -SH
      group of GSH. The -SH group of GSH is expected to attack the peroxy group of
      PGH2, initializing the catalytic reaction transforming PGH2 to prostaglandin E2
      (PGE2). The overall agreement between the calculated and experimental results
      demonstrates that the predicted 3D model could be valuable in future rational
      design of potent inhibitors of mPGES-1 as the next-generation inflammation
      related therapeutic.

PMID- 16439138
TI  - Fluorescent intercalator displacement analyses of DNA binding by the peptide
      derived natural products netropsin, actinomycin, and bleomycin.
AB  - The response of the high-throughput fluorescent intercalator displacement (HT
      FID) assay reported recently by Boger et al. to peptide-based DNA binding
      intercalators and metal complexes was examined through the study of actinomycin
      and Co(III).bleomycin-B2. Along with a validation of netropsin that illustrated
      the good laboratory-to-laboratory reproducibility of the assay, our examination
      of actinomycin revealed results for a four base pair cassette library of DNA
      hairpins that paralleled the known DNA site-selectivity of this agent and also
      indicated the involvement of the flanking sequences of the hairpin
      oligonucleotide. In addition, for Co(III).bleomycin-B2 the established cleavage
      site-selectivity for 5'-GT and 5'-GC sites was correlated to drug-DNA association
      in this binding-only assay; our results also suggest a tetranucleotide site
      selectivity for metallobleomycin involving cross-strand, 'back-to-back' 5'-GT and
      5'-GC sites such as 5'-ACGT and 5'-ACGC.

PMID- 16439139
TI  - Bicyclic carbohydrate-derived scaffolds for combinatorial libraries.
AB  - A bicyclic scaffold derived from the natural monosaccharide d-glucose, and
      possessing several diversity sites, was linked to various resins through the
      primary (C-6) hydroxyl and decorated on the solid phase: the hydroxyl group at C
      4 was functionalized as ester, ether, and carbamate, the amino group in the
      second cycle (C-3' position) was functionalized as amide, sulfonamide, and ureido
      and thioureido-derivatives. The compounds synthesized on the solid phase were
      tested for their antiproliferative activity on tumor cell lines.

PMID- 16439140
TI  - Rates of intestinal absorption of molybdenum in humans.
AB  - The intestinal absorption of molybdenum in healthy human volunteers has been
      measured by simultaneous oral and intravenous administration of the stable
      isotopes 95Mo and 96Mo, and the results were analysed using the convolution
      integral technique. The results showed that molybdenum ingested in liquid form
      was rapidly and totally absorbed into the circulation under ordinary intake
      regimes. The rates and extent of absorption were lower for composite meals, and
      also for increasing levels of administration. This information can be helpful in
      the application of the new ICRP model of the human alimentary tract.

PMID- 16439142
TI  - A hybrid technique of aortic arch branch transposition and antegrade stent graft
      deployment for complete arch repair without cardiopulmonary bypass.
AB  - We describe a minimally invasive technique for complete aortic arch repair
      without cardiopulmonary bypass. A 77-year-old man with severe obstructive airways
      disease presented with aneurysmal disease of his aortic arch. Through a median
      sternotomy and the application of a side-biting clamp, the common trunk of a
      bifurcation Dacron graft was anastomosed to the ascending aorta. The limbs of the
      graft were anastomosed to the innominate and left common carotid arteries,
      respectively. The left subclavian artery was ligated. Two endoluminal stent
      grafts were deployed via a side arm in the Dacron graft, covering the whole arch.
      Completion angiography and transesophageal echocardiography revealed excellent
      seating of both stent grafts, with no endo-leaks. The patient had a rapid,
      uneventful post-operative recovery. Follow-up CT scanning revealed complete
      exclusion of the arch aneurysm.

PMID- 16439141
TI  - Intersecting pathways to neurodegeneration in Parkinson's disease: effects of the
      pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system.
AB  - Sporadic Parkinson's disease (PD) is most likely caused by a combination of
      environmental exposures and genetic susceptibilities, although there are rare
      monogenic forms of the disease. Mitochondrial impairment at complex I, oxidative
      stress, alpha-synuclein aggregation, and dysfunctional protein degradation, have
      been implicated in PD pathogenesis, but how they are related to each other is
      unclear. To further evaluated PD pathogenesis here, we used in vivo and in vitro
      models of chronic low-grade complex I inhibition with the pesticide rotenone.
      Chronic rotenone exposure in vivo caused oxidative modification of DJ-1,
      accumulation of alpha-synuclein, and proteasomal impairment. Interestingly, the
      effects become more regionally restricted such that systemic complex I inhibition
      eventually results in highly selective degeneration of the nigrostriatal pathway.
      DJ-1 modifications, alpha-synuclein accumulation, and proteasomal dysfunction
      were also seen in vitro and these effects could be prevented with alpha
      tocopherol. Thus, chronic exposure to a pesticide and mitochondrial toxin brings
      into play three systems, DJ-1, alpha-synuclein, and the ubiquitin-proteasome
      system, and implies that mitochondrial dysfunction and oxidative stress link
      environmental and genetic forms of the disease.

PMID- 16439143
TI  - Spontaneous tension hydropneumopericardium complicating serofibrinous
      pericarditis.
AB  - A hydropneumopericardium is a rare but critical condition, which is mostly
      ascribed to primary infiltrative lesions from adjacent organs, pericardial
      infections, or trauma. Although there have been reports about
      pyopneumopericardium, no case of spontaneous non-purulent hydropneumopericardium
      has been documented in literature. We report a case of a previously healthy man
      of spontaneously occurred tension hydropneumopericardium complicating
      serofibrinous pericarditis. A surgical exploration followed by partial
      pericardiectomy was performed to stop cardiac tamponade and possible later
      constriction. Remarkably, no definite pathogenesis was identified despite
      surgical and laboratory investigations. The spontaneity and management of
      hydropneumopericardium are discussed.

PMID- 16439144
TI  - Neurophysiological monitoring during thoracoabdominal aortic endovascular stent
      graft implantation.
AB  - OBJECTIVE: The aim of this study was to evaluate the benefit of
      neurophysiological monitoring during thoracic and thoracoabdominal endovascular
      stent graft implantation. METHODS: The spinal cords of 21 patients undergoing
      endovascular stent graft implantation on the thoracic and thoracoabdominal aorta
      were monitored with transcranial motor-evoked potentials (tcMEP) and
      somatosensory-evoked potentials (SSEP). All patients underwent mild systemic
      hypothermia (34-35 degrees C), constant cerebrospinal fluid (CSF) pressure and
      vital parameter monitoring. If CSF pressure exceeded 15 mmHg, CSF-drainage was
      carried out. RESULTS: Three of the 21 patients (14%) exhibited short-term loss of
      tcMEP and SSEP after the deployment of the self-expanding endoprosthesis. We
      observed an intraoperative recovery of the evoked potentials in all cases. CSF
      drainage was necessary in three of them. One patient, whose potentials were
      stable intraoperatively, developed paraparesis 3 weeks after the intervention.
      CONCLUSIONS: Neurophysiological monitoring has proved to be an ideal monitoring
      method to detect spinal cord ischemia during thoracic and thoracoabdominal
      endovascular stent graft implantation. Due to the advantages of endovascular
      therapy (no aortic cross-clamping, continuous distal perfusion, and no
      reperfusion injury), changes in potentials were seldom observed.

PMID- 16439145
TI  - Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary
      artery bypass grafting.
AB  - OBJECTIVE: It has been observed that a systemic inflammatory response after on
      pump coronary artery bypass grafting (CABG) participates in the pathogenesis of
      postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it
      is plausible that inflammation is associated with the development of
      postoperative AF. The present study examined relation of proinflammatory
      cytokines, which play an important role in the upstream of inflammatory cascade,
      to the development of AF after off-pump CABG. METHODS: The present study included
      39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay,
      on anesthetic induction, after sternotomy before anastomoses, at the completion
      of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C
      reactive protein (CRP) was also measured by turbidimetric immunoassay,
      preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%)
      developed postoperative AF. Patients with postoperative AF were older (70+/-6.4
      years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre-
      and perioperative variables. TNF-alpha level did not change during the study
      period. However, IL-8 and CRP levels significantly increased after the surgery,
      although there was no significant difference between the two groups. IL-6 level
      also increased after the surgery with its peak at 6h after the completion of
      anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher
      in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047,
      435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression
      analysis indicated that the highest quartile of IL-6 level immediately after the
      surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18;
      95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore,
      the maximum level of IL-6 immediately after the surgery significantly correlated
      to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04,
      respectively). CONCLUSIONS: Advanced age was a major risk factor for
      postoperative AF. Furthermore, inflammatory response induced by surgical trauma
      was also associated with the development of AF after off-pump CABG.

PMID- 16439146
TI  - Antithrombin activity in children with chylothorax.
AB  - OBJECTIVE: To determine whether increased antithrombin loss is present in
      children with chylothorax after cardiac surgery. METHODS: Plasma and pleural
      effusion samples of children with chylous and non-chylous pleural effusion were
      assayed for antithrombin activity. RESULTS: Ten children with chylothorax and
      five children with non-chylous pleural effusion were investigated. There was
      statistically significant increase in mean antithrombin activity in chylous
      samples (32.2+/-11.4%) compared to non-chylous samples (14.4+/-13.9%), and
      significant decrease in plasma of children with chylothorax (44.6+/-15.4%)
      compared to children with non-chylous pleural effusion (69.9+/-22.4%). Seven of
      10 children with chylous and none of the children without chylous developed
      thrombosis (p<0.007). CONCLUSIONS: Increased loss of antithrombin is present in
      children with chylothorax, potentially predisposing these children to an
      increased risk of thrombosis. Repeated antithrombin substitution should be
      considered in critically ill children with chylothorax.

PMID- 16439147
TI  - First year changes of myocardial lymphatic endothelial markers in heart
      transplant recipients.
AB  - OBJECTIVE: The lymphatic system plays an important role in interstitial fluid
      balance, lipid metabolism, and immune response. The recent introduction of
      specific lymphatic endothelial cell markers has made the investigation of
      lymphangiogenesis under various conditions and from small tissue samples
      feasible. It was the purpose of the study to investigate the changes of
      myocardial lymphatic endothelial markers during the first 12 months after heart
      transplantation and to analyze if a correlation between lymphatic markers and
      rejection can be found. METHODS: Right ventricular endomyocardial biopsies taken
      for routine rejection monitoring from 26 heart transplant recipients were
      investigated. Selected time points were 0.5, 1, 1.5, 6, and 12 months after human
      heart transplantation (HTX). Immunohistostaining was performed for VEGFR-3, the
      receptor for lymphangiogenic vascular endothelial growth factors C and D, for
      LYVE-1, a novel hyaluronan receptor, restricted to lymphatic vessels, and PROX-1,
      a homeobox gene product, which plays a key role in lymph vessel development and
      differentiation. RESULTS: Density of VEGFR-3 positive lymphatics did not change
      during the first 12 months after transplantation. However, in comparison to the
      0.5-month biopsy, density of LYVE-1 and PROX-1 positive lymphatics was
      significantly decreased at 1 month after transplantation (p<0.03) and at the
      subsequent time points (p<0.01). Patients with only moderate rejection during the
      first 12 months (ISHLT<IIIa) had a significantly higher density of VEGFR-3 at 0.5
      month in comparison to patients with at least one episode of clinically relevant
      rejection (ISHLT IIIa or worse, p<0.03). CONCLUSION: Myocardial lymphatics show a
      significant change of endothelial phenotype after transplantation, as
      demonstrated by significant quantitative changes of lymphatic endothelial marker
      density. Patients with at least one rejection of ISHLT IIIa or higher had a
      significantly lower density of VEGFR-3 at 0.5 month after transplantation. The
      results of this study warrant further investigation on the impact of
      transplantation on the lymphatic endothelium. The cause-effect relation between
      rejection and lymphatic endothelium remains to be investigated.

PMID- 16439148
TI  - Bronchoscopic procedures for emphysema treatment.
AB  - Emphysema is a debilitating lung disease continuing to be a major source of
      morbidity and mortality in the developed countries. Medical treatment is the
      mainstay of therapy and consists of smoking cessation, pulmonary rehabilitation,
      administration of bronchodilators and, when indicated, steroids and supplemental
      oxygen. Various surgical procedures have been promoted in the past to relieve
      dyspnoea and improve quality of life in patients with advanced emphysema; whilst
      early results were often encouraging, a sustained objective functional
      improvement was rarely achieved and most of those procedures were progressively
      abandoned. Despite controversies, LVRS has been shown to be beneficial to
      selected patients with end-stage emphysema when medical therapy has failed. There
      is no doubt that LVRS allows a significative functional improvement in a selected
      group of patients; however, it still carries a substantial morbidity, even if
      mortality is low at the centres with the larger experience. Patients with a most
      advanced functional deterioration show a higher surgical mortality and less
      impressive functional results, suggesting that LVRS should be considered more
      carefully in these situations. Bronchoscopic alternatives to the surgical
      approach have been recently proposed and some of them may play an important role
      in the future; in particular, the airway bypass and bronchoscopic lung volume
      reduction with one-way valves are certainly one step beyond on their way to
      clinical application. We hereby report the initial experimental and clinical
      experience with these new treatment options.

PMID- 16439149
TI  - Giant aneurysm of an aortocoronary saphenous bypass graft.

PMID- 16439150
TI  - Effect of lung ischemia--reperfusion on oxidative stress parameters of remote
      tissues.
AB  - OBJECTIVE: Ischemia-reperfusion injury induces a systemic inflammatory response
      and production of reactive oxygen species, which potentially can be more
      detrimental than its local effects. Although the lung injury that is formed by
      the effects of ischemia-reperfusion injury on remote organs has been previously
      studied, no previous study that investigated the effects of pulmonary ischemia
      reperfusion injury on remote organs has been considered. We hypothesized that the
      lung ischemia-reperfusion injury may cause the spread of inflammation to remote
      organs such as liver and heart. METHODS: Thirty New Zealand white rabbits were
      subjected to either sham operation or lung ischemia-reperfusion injury in various
      periods of time (60 min ischemia-60 min reperfusion and 120 min ischemia-60 min
      reperfusion, respectively). Pulmonary, myocardial and hepatic myeloperoxidase,
      protein sulfhydryl, thiobarbituric acid-reactive substances, and protein carbonyl
      levels were evaluated to show pulmonary, hepatic, and myocardial responses to
      lung ischemia-reperfusion injury. RESULTS: Reperfusion after 60 min of lung
      ischemia led to increased myeloperoxidase and protein carbonyl levels and
      decreased protein sulfhydryl groups in pulmonary tissue, increased
      myeloperoxidase and decreased protein sulfhydryl groups in hepatic tissue, and
      increased myeloperoxidase, thiobarbituric acid-reactive substances and protein
      carbonyl levels in myocardial tissue. Reperfusion after 120 min of lung ischemia
      led to increased thiobarbituric acid-reactive substance levels in pulmonary
      tissue, increased protein carbonyl and thiobarbituric acid-reactive substance
      levels in hepatic tissue, and decreased protein sulfhydryl groups in myocardial
      tissue. CONCLUSIONS: The data of the present study suggests that pulmonary
      ischemia-reperfusion induces liver and heart injury characterized by activated
      neutrophil sequestration and release of significant amounts of reactive oxygen
      species. The remote organ injury has to be kept in mind when performing a lung
      intervention or surgery and care should be taken to protect other organs remote
      from ischemia-reperfusion site.

PMID- 16439151
TI  - Serial angiographic follow-up of grafts one year and five years after coronary
      artery bypass surgery.
AB  - OBJECTIVE: We studied retrospectively the patency of grafts after coronary artery
      bypass grafting (CABG) using serial angiographies performed one year and five
      years after surgery. METHODS: One hundred and nine patients who had available
      coronary angiographies at both one year and five years after CABG were included.
      Morphologic changes of anastomotic sites and grafts were traced in the same group
      of patients using the FitzGibbon grading system. RESULTS: The arterial graft
      patency rate (FitzGibbon grade A+B) was significantly higher than the saphenous
      vein grafts at both one year (98.0% vs 82.4%, p<0.001) and five years (90.7% vs
      80.2%, p=0.006) after surgery, respectively. The arterial graft patency rate was
      superior to vein grafts in the left anterior descending coronary artery territory
      at both one year (97.5% vs 82.0%, p=0.001) and five years (90.9% vs 78.0%,
      p=0.042) postoperatively. Other territories showed similar patency rates between
      arterial and vein grafts. The vein graft patency rate at five years
      postoperatively was lowest in the right coronary territory when compared with
      other territories. When the patency pattern was compared between postoperative
      years 1 and 5, the proportion of FitzGibbon grade B grafts increased
      significantly in the vein grafts (3.1% vs 7.5%, p=0.002), while that of arterial
      grafts remained stable (8.6% vs 7.3%, p=0.774). When the graft patency at
      postoperative year 5 was compared between patients with recurrent angina and
      those without, the patients with recurrent angina showed a higher proportion of
      FitzGibbon grade B grafts (19.2% vs 4.8% in arterial grafts, p=0.023; 20.5% vs
      4.8% in vein grafts, p=0.003) and lower grade A grafts (65.4% vs 86.4% in
      arterial grafts, p=0.019; 43.6% vs 78.2% in vein grafts, p<0.001), and a lower
      vein graft patency rate (64.1% vs 83.0%, p=0.014). CONCLUSIONS: The arterial
      graft patency rate was significantly higher than that of saphenous vein grafts,
      especially in the left anterior descending coronary artery territory, at one year
      and five years postoperatively. The decreased patency rate of the vein grafts,
      along with insulin-dependent diabetes mellitus, were associated with angina
      recurrence.

PMID- 16439152
TI  - Influence of time elapsed between myocardial infarction and coronary artery
      bypass grafting surgery on operative mortality.
AB  - OBJECTIVE: Optimal timing for CABG surgery after myocardial infarction (MI)
      remains controversial. We examined the influence of patient age and time elapsed
      between MI and isolated CABG surgery on operative mortality. METHODS:
      Perioperative data of 13,545 patients who underwent isolated CABG surgery from
      1991 to 2005 were reviewed. A previous MI was found in 7219 patients, classified
      among groups A-E whether they underwent surgery less than 6h (A, n=26), between 6
      and 24h (B, n=51), between 1 and 7 days (C, n=313), between 8 and 30 days (D,
      n=917), or more than 30 days (E, n=5912) after the event. Crude percentages and
      odds ratio estimates of operative mortality were calculated. RESULTS: In patients
      who had no history of MI, the mortality rate was 1.7%, while it was,
      respectively, 19.2, 9.8, 8.6, 3.2, and 2.4% in patients from groups A to E. Among
      6589 patients over 65 years of age, 3027 had no history of MI. Their mortality
      was 2.4%, compared to, respectively, 35.7, 13.8, 11.3, 5.1, and 3.9% for those
      belonging to groups A-E. Overall odds ratio estimates of operative mortality were
      3.92 (p=0.19), 5.08 (p=0.002), 4.33 (p=0.0001), 1.50 (p=0.08), and 1.18 (p=0.24)
      for groups A-E, respectively. CONCLUSIONS: Operative mortality is not influenced
      by a history of MI sustained more than 30 days prior to isolated CABG surgery,
      but is highly and most significantly increased between 6h and 1 week after MI,
      especially in older patients. That critical period should be avoided whenever
      possible.

PMID- 16439153
TI  - A clinical study of annular geometry and dynamics in patients with ischemic
      mitral regurgitation: new insights into asymmetrical ring annuloplasty.
AB  - OBJECTIVE: Recent studies in animals showed that regional annulus distortion is a
      major determinant of ischemic mitral regurgitation (IMR) and accordingly
      suggested new surgical approaches with asymmetrical annuloplasty rings. As
      accurate measurement of annulus in patients is still a challenge, we performed
      this study to analyze the changes in three-dimensional annular geometry in
      patients with IMR compared to primary valvular lesions. METHODS: We studied 110
      patients divided into three groups: (1) 30 with coronary artery disease without
      IMR, (2) 38 with chronic IMR, and (3) 42 with MR due to primary valvular lesions.
      Longitudinal and septal-lateral annulus diameters; global diastolic and systolic
      annular area and its percentual shortening, diastolic and systolic areas of six
      regions corresponding to the segmental Carpentier classification were measured by
      3D-echocardiography. The degree of MR was assessed by three-dimensional color
      Doppler. Global and regional left ventricular geometry were assessed by
      sphericity index and by measuring anterior and posterior tethering of papillary
      muscles. RESULTS: Patients with significant IMR (group 2) showed larger
      longitudinal (52.7+/-3.9 mm vs 41.8+/-2.9 mm; p<0.01) and antero-lateral (31.8+/
      3.5mm vs 26.7+/-2.8mm; p<0.01) annular diameters than the patients with MR due to
      primary valvular lesions (group 3). Diastolic (997.8+/-64.9 mm(2) vs 700.7+/
      46.8mm(2); p<0.01) and systolic (894.9+/-57.3mm(2) vs 547.3+/-35.0mm(2); p<0.01)
      annular areas were larger in group 2 than in group 3. Annular area change was
      significantly lower in the group with ischemic mitral regurgitation than in the
      group with primary valvular lesions (10.3+/-1.1% vs 21.9+/-1.6%; p<0.01).
      Regional annular areas of the six sectors were homogeneously larger in group 2
      than in group 3. The sector P3 did not show larger area than the other ones. The
      degree of MR, as assessed by the volumes of regurgitant jets, was higher in the
      group with primary valvular lesions than in the patients with IMR (32.6+/-13.4
      cm(3) vs 23.1+/-11.1cm(3); p<0.01). CONCLUSIONS: This study showed that annular
      enlargement in patients with IMR affects the different annular regions to the
      same extent. An ideal surgical repair of IMR should be individually tailored
      after quantitative assessment measurement of geometry and function of each single
      component of the mitral valve complex.

PMID- 16439154
TI  - A vascular tube for intercostal artery reimplantation.
AB  - Paraplegia and paraparesis are major concerns in descending and thoracoabdominal
      aortic repair. A shorter period of spinal cord ischemia is preferred for
      protection. We have developed a new technique in which plural intercostal
      arteries are reattached in a short time. The lower descending aorta is tailored
      using automatic sutures, and a vascular tube is made with diameter about 2.0 cm.
      Blood supply of intercostal arteries including the Adamkiewicz artery is resumed
      by perfusing the vascular tube in not more than 20 min. This technique has been
      applied in four patients, and there was neither paraplegia nor paraparesis.

PMID- 16439155
TI  - Right ventricular outflow tract reconstruction using Contegra valved conduit:
      natural history and conduit performance under pressure.
AB  - OBJECTIVE: To assess the performance of the bovine Contegra valved conduit used
      for right ventricular (RV) outflow tract reconstruction, particularly in relation
      to post-operative RV pressure. METHODS: Follow-up study of 64 consecutive right
      ventricular to pulmonary artery-conduit implants in 62 patients between January
      2000 and April 2003. The majority of cases were forms of pulmonary atresia/VSD
      (n=24, 39%) or Fallot's tetralogy (n=13, 21%). Thirteen cases (21%) had aortic
      atresia, truncus arteriosus or discordant connections with pulmonary atresia/VSD.
      Twelve cases (19%) were conduit replacements. Echocardiography was performed for
      a median follow-up of 14 months (range 0-38 months). RESULTS: Median age at
      implantation was 13.8 months (range 0.1-244 months) and median weight was 8.9 kg
      (range 2.1-84.1 kg). Thirty-eight patients (59.4%) were <10 kg at the time of
      surgery. Early mortality was 6.4% (n=4). During follow-up there were four
      explantations (one for endocarditis and three for conduit dilatation) and 16
      (28.6%) catheter interventions. Overall freedom from intervention at 1 and 3
      years was 71+/-6% and 53+/-11%, respectively. Freedom from conduit-specific
      reintervention was 66+/-11% at the end of the study period. Reintervention was
      associated with small conduits (p=0.04), age <1 year (p=0.04) and with high RV/LV
      pressure ratio in the immediate post-operative period (p=0.0003). On multivariate
      analysis, the RV/LV pressure ratio was the strongest single factor predicting the
      overall reintervention (OR 5.45). Acquired distal conduit stenosis at suture line
      was the commonest indication for conduit-specific reintervention and was
      associated with the smaller conduits. The conduits explanted for dilatation
      showed neointimal proliferation, thrombosis, calcification and chronic
      inflammation. CONCLUSIONS: The Contegra conduit is widely applicable to RVOT
      reconstruction with satisfactory mid-term results. However, there is a
      significant incidence of conduit-related complications, particularly with the
      smaller conduits. Adverse performance was strongly associated with high RV/LV
      pressure ratio at completion of surgery. We would recommend cautious use of the
      conduits in patients with predicted high RV/LV pressure ratios, where careful
      monitoring of conduit performance is crucial. There is some element of
      unpredictability, which adds to the importance of close follow-up. Further
      studies are needed to explore the issues of thrombogenicity, degeneration,
      possible 'rejection', and the potential role of anti-platelet and anti
      inflammatory modulation.

PMID- 16439156
TI  - Expression and purification of the synthetic preS1 gene of Hepatitis B Virus with
      preferred Escherichia coli codon preference.
AB  - To produce high levels of hepatitis B virus (HBV) preS1 protein at low cost, a
      DNA fragment encoding the preS1 region, residues 1-119, of HBV adr subtype was
      synthesized by overlapping-PCR according to Escherichia coli (E. coli) B
      preferred codon usage. The synthetic preS1 gene (spreS1) was cloned into the
      bacterial expression vector pET-30a and transferred into the expression strain E.
      coli BL21(DE3). Recombinant preS1 protein with an N-terminal His6 tag was
      expressed at high levels in soluble form, yielding about 44% of the total
      cellular protein. This technique overcomes problems that existed in previously
      reported expression systems of preS1 or its epitope, i.e., low-level expression
      or expression in inclusion bodies. Using this His-tagged preS1 expression system,
      recombinant protein was purified by single-step affinity chromatography on a Ni
      NTA column resulting in a yield was about 28 mg recombinant protein per liter
      culture. Furthermore, Western blotting and indirect ELISA analysis demonstrate
      that the reactivity of preS1-specific antibody is comparable between the
      recombinant and commercialized preS1 protein. Thus, our improved expression
      system could be used for practical, low-cost large-scale production of
      recombinant preS1 without refolding steps.

PMID- 16439157
TI  - On the structural features of hairpin triloops in rRNA: from nucleotide to global
      conformational change upon ligand binding.
AB  - RNA structure can be viewed as both a construct composed of various structural
      motifs and a flexible polymer that is substantially influenced by its
      environment. In this light, the present paper represents an attempt to reconcile
      the two standpoints. By using the 3D structures both of four (16S and 23S)
      portions of unbound 50S, H50S, and T30S ribosomal subunits and of 38 large
      ribonucleoligand complexes as the starting point, the behavior, which is induced
      by ligand binding, of 73 hairpin triloops with closing g-c and c-g base pairs was
      investigated using root-mean-square deviation (RMSD) approach and pseudotorsional
      (eta,theta) convention at the nucleotide-by-nucleotide level. Triloops were
      annotated in accordance with a recent proposal of geometric nomenclature. A
      simple measure for the determination of the strain of a triloop is introduced. It
      is believed that a possible classification of the interior triloops, based on the
      2D eta-theta unique path, will aid to conceive their local behavior upon ligand
      binding. All rRNA residues in contact with ligands as well as regions of
      considerable conformational changes upon complex formation were identified. The
      analysis offers the answer to: how proximal to and how far from the actual ligand
      binding sites the structural changes occur?

PMID- 16439158
TI  - The role of the extrapersonal brain systems in religious activity.
AB  - The neuropsychology of religious activity in normal and selected clinical
      populations is reviewed. Religious activity includes beliefs, experiences, and
      practice. Neuropsychological and functional imaging findings, many of which have
      derived from studies of experienced meditators, point to a ventral cortical axis
      for religious behavior, involving primarily the ventromedial temporal and frontal
      regions. Neuropharmacological studies generally point to dopaminergic activation
      as the leading neurochemical feature associated with religious activity. The
      ventral dopaminergic pathways involved in religious behavior most closely align
      with the action-extrapersonal system in the model of 3-D perceptual-motor
      interactions proposed by . These pathways are biased toward distant (especially
      upper) space and also mediate related extrapersonally dominated brain functions
      such as dreaming and hallucinations. Hyperreligiosity is a major feature of
      mania, obsessive-compulsive disorder, schizophrenia, temporal-lobe epilepsy and
      related disorders, in which the ventromedial dopaminergic systems are highly
      activated and exaggerated attentional or goal-directed behavior toward
      extrapersonal space occurs. The evolution of religion is linked to an expansion
      of dopaminergic systems in humans, brought about by changes in diet and other
      physiological influences.

PMID- 16439159
TI  - Modulation of [18F]fluorodopa (FDOPA) kinetics in the brain of healthy volunteers
      after acute haloperidol challenge.
AB  - In animal studies, acute antipsychotic treatment was shown to enhance striatal
      DOPA-decarboxylase (DDC) activity. However, this phenomenon has not been
      demonstrated in humans by positron emission tomography (PET). Therefore, we
      investigated acute haloperidol effects on DDC activity in humans using
      [18F]fluorodopa (FDOPA) PET. Nine healthy volunteers were scanned with FDOPA in
      drug-free baseline conditions and after 3 days of haloperidol treatment (5
      mg/day). A continuous performance test (CPT) was administered in both conditions.
      The net blood-brain clearance of FDOPA (K(in)app) in striatum, mesencephalon, and
      medial prefrontal cortex was calculated by volume-of-interest analysis. The
      macroparameter K(in)app is a composite of several kinetic terms defining the
      distribution volume of FDOPA in brain (V(e)D) and the relative activity of DOPA
      decarboxylase (k3D). Therefore, compartmental kinetic analysis was used to
      identify the physiological basis of the observed changes in K(in)app period. The
      magnitude of K(in)app was significantly increased in the putamen (18%) and
      mesencephalon (36%). Furthermore, V(e)D in the brain was increased by 15%.
      Increments of k3(D) in the basal ganglia did not attain statistical significance.
      The significant worsening of CPT results did not correlate with changes in FDOPA
      utilization. The present PET results indicate potentiation of FDOPA utilization
      in human basal ganglia by acute haloperidol treatment, apparently due to
      increased availability throughout the brain. The stimulation of DDC cannot be
      excluded due to insufficient statistical power in the estimation of k3(D)
      changes.

PMID- 16439160
TI  - Vicariance, colonisation, and fast local speciation in Asia Minor and the Balkans
      as revealed from the phylogeny of spined loaches (Osteichthyes; Cobitidae).
AB  - We reconstruct the phylogeny of the morphologically diagnosable subgenera
      Bicanestrinia, Beysehiria, and Cobitis sensu stricto of the genus Cobitis from
      Asia Minor and the Balkans. We used the complete cytochrome b gene of 65
      specimens in order to infer their evolutionary history in this zoogeographically
      interesting area. Our phylogeographic analysis did not evidence the previously
      suggested monophyly of the Bicanestrinia subgenus but revealed five monophyletic
      lineages in the area: the lineages Bicanestrinia I-IV including all species of
      Bicanestrinia plus the lineage Cobitis s. str. The monotypic subgenus Beysehiria
      from Lake Beysehir in Anatolia was closely related to the syntopic population of
      C. turcica and nested inside the lineage Bicanestrinia III. The strictly
      allopatric distribution of the four lineages of Bicanestrinia suggests that
      vicariance has played a major role in the diversification of Bicanestrinia. All
      analysed species of Cobitis s. str. from Asia Minor and Balkans were closely
      related to Cobitis s. str. from Central Europe, the Danube basin and the
      Caucasus, indicating at least two colonisation events into Asia Minor and the
      Balkans. A third, recent colonisation event led to the presence of C. strumicae,
      generally restricted to the Aegean Sea drainage, in the Danube basin. Besides the
      evidences of vicariance and colonisation events in the phylogenetic history of
      the genus Cobitis in Asia Minor and the Balkans, our analysis suggested also a
      rapid morphological evolution of C. bilseli in a lacustrine environment.
      Application of Cobitis mitochondrial cytochrome b clocks of 0.68% sequence
      divergence per million years (MY) suggest that the split between the five major
      lineages happened approximately 12.4-17.6 MYA, and according to the lack of basal
      resolution of this monophyletic group probably the split of all lineages happened
      within a narrow time window.

PMID- 16439161
TI  - Expansion of the SOX gene family predated the emergence of the Bilateria.
AB  - Members of the SOX gene family are involved in regulating many developmental
      processes including neuronal determination and differentiation, and in
      carcinogenesis. So far they have only been identified in species from the
      Bilateria (deuterostomes and protostomes). To understand the origins of the SOX
      family, we used a PCR-based strategy to obtain 28 new sequences of SOX gene HMG
      domains from four non-bilaterian Metazoa: two sponge species, one ctenophore and
      one cnidarian. One additional SOX sequence was retrieved from EST sequences of
      the cnidarian species Clytia hemisphaerica. Unexpected SOX gene diversity was
      found in these species, especially in the cnidarian and the ctenophore. The
      topology of gene relationships deduced by Maximum Likelihood analysis, although
      not supported by bootstrap values, suggested that the SOX family started to
      diversify in the metazoan stem branch prior to the divergence of demosponges, and
      that further diversification occurred in the eumetazoan branch, as well as later
      in calcisponges, ctenophores, cnidarians and vertebrates. In contrast, gene loss
      appears to have occurred in the nematode and probably in other protostome
      lineages, explaining their lower number of SOX genes.

PMID- 16439162
TI  - Genetic structure and historical demography of the shanny Lipophrys pholis in the
      Portuguese coast based on mitochondrial DNA analysis.

PMID- 16439164
TI  - The evolution of Dactylorhiza (Orchidaceae) allotetraploid complex: insights from
      nrDNA sequences and cpDNA PCR-RFLP data.
AB  - Sequence data from a portion of the external transcribed spacer (ETS) and from
      the internal transcribed spacers (ITS1 and ITS2) of 18S-26S nuclear ribosomal DNA
      were used together with chloroplast DNA PCR-RFLP data to unravel patterns of
      allotetraploid speciation within the Western European Dactylorhiza polyploid
      complex. A maximum likelihood tree based on combined ETS and ITS sequences
      suggests that the Western European Dactylorhiza allotetraploids have evolved by
      hybridization between four main diploid lineages. Cloned sequences and the
      topology of the ITS plus ETS tree indicate that the allotetraploid species D.
      elata, D. brennensis, and D. sphagnicola have originated from the autotetraploid
      D. maculata together with the diploid D. incarnata, while D. majalis, D.
      traunsteineri, and D. angustata seem to have evolved by hybridization between the
      D. fuchsii s.str and D. incarnata lineages. Finally, the diploid D. saccifera
      lineage seems to have been involved together with the D. incarnata lineage in the
      formation of the allotetraploid D. praetermissa. The observed congruence between
      the chloroplast tree and the ITS/ETS tree suggests a directional evolution of the
      nrDNA after polyploidization in favor of the maternal genome. Considered together
      with morphological, biogeographical, and ecological evidence, the molecular
      analysis leads us to recognize four species within the investigated
      allotetraploid complex, namely D. majalis, D. praetermissa, D. elata, and D.
      sphagnicola.

PMID- 16439163
TI  - Phylogeny and biogeography of Altingiaceae: evidence from combined analysis of
      five non-coding chloroplast regions.
AB  - The Altingiaceae consist of approximately 15 species that are disjunctly
      distributed in Asia and North America. The genus Liquidambar has been employed as
      a biogeographic model for studying the Northern Hemisphere intercontinental
      disjunctions. Parsimony and Bayesian analyses based on five non-coding
      chloroplast regions support that (1) Liquidambar is paraphyletic; (2) the
      temperate Liquidambar acalycina and Liquidambar formosana are nested within a
      large tropical to subtropical Asian clade; (3) Semiliquidambar is scattered in
      the eastern Asian clade and is of hybrid origin involving at least two maternal
      species: L. formosana and L. acalycina; and (4) the eastern North American
      Liquidambar styraciflua groups with the western Asian Liquidambar orientalis, but
      is highly distinct from other lineages. Biogeographically, our results
      demonstrate the complexity of biogeographic migrations throughout the history of
      Altingiaceae since the Cretaceous, with migration across both the Bering and the
      North Atlantic land bridges.

PMID- 16439165
TI  - Oxcarbazepine reduces seizure frequency in a high proportion of patients with
      both newly diagnosed and refractory partial seizures in clinical practice.
AB  - The antiepileptic efficacy and tolerability of oxcarbazepine, used both as
      monotherapy and adjunctive therapy, were observed for 1 year in 202 adult
      patients, aged 17-83 years, with newly diagnosed or refractory partial epilepsy
      in clinical practice in Italy. At first observation, the seizure free rate was
      72.2% in newly diagnosed patients given monotherapy, 40% in patients in whom
      oxcarbazepine replaced another monotherapy and 10.3% in patients given
      oxcarbazepine as adjunctive therapy. At least 50% reduction in seizure frequency
      was achieved in 90.7, 72 and 57%, respectively. Efficacy increased with the
      duration of treatment (p < 0.0001). In the 160 completers the seizure free rate
      was 61.3% with monotherapy and 28% with adjunctive therapy. 16.3% of patients
      reported adverse effects, mainly sedation and sleepiness; 5% discontinued
      oxcarbazepine because of adverse events. OXC is an effective and well-tolerated
      antiepileptic agent for the long-term treatment of partial epilepsy in adults.

PMID- 16439166
TI  - Neural circuits mediating latent learning and conditioning for salt in the rat.
AB  - Male Long-Evans rats alternately drank a salt solution in one distinctive
      compartment of a conditioned cue preference (CCP) apparatus and water in a
      different compartment over 8 days (training trials) and were then given a choice
      between the two compartments with no solutions present (test trial). Rats that
      were water deprived during training, then salt+water deprived during testing,
      spent more time in their salt-paired compartments, a salt latent cue preference
      (LCP). Rats that were water-only deprived during training and testing spent more
      time in their water-paired compartments, a water CCP. Rats that were salt+water
      deprived during both training and testing spent more time in their salt-paired
      compartments, a salt CCP. Bilateral, pre-training lesions of the lateral amygdala
      impaired the water and salt CCPs but not the salt LCP, reflecting the role of the
      amygdala in Pavlovian conditioning. Lesions of the dorsal or ventral hippocampus
      impaired the salt LCP and the water and salt CCPs, possibly reflecting the role
      of the hippocampus in contextual learning. Lesions of the fimbria-fornix impaired
      the water and salt CCPs but not the salt LCP, while lesions of the entorhinal
      cortex impaired the salt LCP but not the CCPs. This suggests that the LCP depends
      on a circuit that includes dorsal and ventral hippocampus and entorhinal cortex,
      a major conduit of sensory information from the cortex. In contrast, the CCPs
      depend on the amygdala and a circuit that includes the hippocampus and fimbria
      fornix, possibly as a conduit of motivational information from subcortical
      structures.

PMID- 16439167
TI  - The use of a percutaneous closure device for closure of an accidental puncture of
      the aortic arch; a simple solution for a difficult problem.
AB  - Percutaneous closure devices are now often used for closure of the femoral
      puncture site after percutaneous vascular interventions. We describe a case were
      an accidental puncture in the aortic arch during placement of a central venous
      catheter is successfully closed with a closure device.

PMID- 16439168
TI  - Endovascular treatment of ruptured and symptomatic abdominal aortic aneurysms.
AB  - OBJECTIVE: To report the experience of endovascular repair (ER) in patients with
      ruptured and symptomatic abdominal aortic aneurysms (rAAA and sAAA), comparing
      results with a cohort of controls who underwent open repair (OR) of sAAA or rAAA.
      DESIGN: A historically controlled cohort study. MATERIALS: Retrospective data
      from 21 patients who underwent ER and prospective data from 23 patients who
      underwent OR. METHODS: Results were compared using the Mann-Whitney U-test.
      RESULTS: Eleven ER patients had sAAAs and 10 had rAAAs. Nine OR patients had
      rAAAs and 13 had sAAAs. Thirty-day mortality was 11% in patients with rAAA in the
      ER group, and 54% in the OR group (p=0.03). There were no post-operative deaths
      in the patients who had an sAAA in the ER group, and one death in the patients
      who had sAAA in the OR group. Results as expressed as mean ER value versus mean
      OR value and p-value. ER was associated with significant reductions in the length
      of operation (2.6 versus 3.1h, p=0.03), blood transfusion requirements (0.86
      versus 10.7 units p<0.01), time in critical care (1.5 versus 6.1 days, p=0.02),
      and total hospital stay (8.5 versus 17.5 days, p=0.01) compared with OR. There
      was no difference in time from admission to arrival in theatre between the two
      groups (3.4 versus 5.0h, p=0.35). CONCLUSIONS: In patients with rAAA and sAAA
      that are suitable for stenting, ER has reduced mortality compared with open
      repair. Assessment for ER does not cause a pre-operative delay, operating time is
      reduced, blood transfusion requirements are reduced and there is a faster
      recovery.

PMID- 16439169
TI  - Wiring specificity in the olfactory system.
AB  - The fruitfly brain learns about the olfactory world by reading the activity of
      about 50 distinct channels of incoming information. The receptor neurons that
      compose each channel have their own distinctive odour response profile governed
      by a specific receptor molecule. These receptor neurons form highly specific
      connections in the first olfactory relay of the fly brain, each synapsing with
      specific second order partner neurons. We use this system to discuss the logic of
      wiring specificity in the brain and to review the cellular and molecular
      mechanisms that allow such precise wiring to develop.

PMID- 16439171
TI  - A cost-benefit analysis of culling badgers to control bovine tuberculosis.
AB  - Bovine tuberculosis (TB) is an important economic problem. The incidence of TB in
      cattle herds has steadily risen in the UK, and badgers are strongly implicated in
      spreading disease. Since the mid-1970s the UK government has adopted a number of
      badger culling strategies to attempt to reduce infection in cattle. In this
      report, an established model has been used to simulate TB in badgers,
      transmission to cattle, and control by badger culling. Costs were supplied by the
      UK Government's Department for Environment Food and Rural Affairs (Defra) for
      badger trapping and gassing. Regardless of culling intensity or area simulated,
      an overall reduction in the herd breakdown rate was seen. With a high culling
      efficacy and no social perturbation, the mean Net Present Value of a few
      simulated culling strategies in an "ideal world" was positive, meaning the
      economic benefits outweighed the costs. Further work is required before these
      results could be considered definitive, as it is necessary to evaluate
      uncertainties and simulate less than perfect conditions.

PMID- 16439170
TI  - The effect of intravenous magnesium hypophosphite in calcium borogluconate
      solution on the serum concentration of inorganic phosphorus in healthy cows.
AB  - The goal of this study was to determine the effect of intravenous (IV)
      administration of phosphite on the serum concentration of inorganic phosphorus in
      cows. Twelve clinically healthy cows were divided into four groups of three. All
      cows received 600 mL of a 40% calcium borogluconate solution; three cows each
      received this as a rapid (20 min) IV infusion with and without 6% magnesium
      hypophosphite, and three other cows each received this as a slow IV infusion (8
      h) with and without 6% magnesium hypophosphite. Samples of blood were collected
      for the determination of serum concentrations of calcium, inorganic phosphorus
      and magnesium before and 10, 20, 40, 60 and 90 min and 2, 3, 4, 5, 6, 7, 8, 24,
      48 and 72 h after the start of treatment. The concentration of calcium increased
      after treatment in all cows but the increase was most rapid in cows that received
      the rapid infusion. In cows that received the rapid IV infusion containing
      magnesium hypophosphite, the mean concentration of inorganic phosphorus decreased
      significantly 3-4 h after treatment compared with initial serum levels. The serum
      concentration of inorganic phosphorus did not change significantly in cows that
      received the rapid IV solution without magnesium hypophosphite or the slow IV
      infusion with or without magnesium hypophosphite. The serum concentration of
      magnesium increased after treatment in all cows receiving magnesium hypophosphite
      but remained unchanged in the others. The rapid infusion of calcium borogluconate
      without magnesium hypophosphite made all three cows anorexic and hypercalcaemic
      and the slow infusion made 1/3 anorexic. It is concluded that the IV
      administration of a calcium solution containing magnesium hypophosphite does not
      increase the serum concentration of inorganic phosphorus.

PMID- 16439172
TI  - Two cases of autosomal recessive generalized dystonia in childhood: 5 year follow
      up and bilateral globus pallidus stimulation results.
AB  - We report two brothers with an unknown form of early-onset familiar dystonia.
      Characteristic clinical features are (1) childhood-onset; (2) extrapyramidal
      motor symptoms; (3) dysarthria; and (4) mental retardation. Additional findings
      include loss of D(2)-receptors in both basal ganglia and hypoplasia of the
      cerebellar vermis with dilatation of the fourth ventricle and cisterna magna.
      There seems to be a progressive and non-progressive form of this clinical entity.
      Dystonic symptoms of the progressive form that occurred in one of the brothers
      were alleviated dramatically by bilateral internal globus pallidus (Gpi)
      stimulation, and the improvement has lasted now for 5 years.

PMID- 16439173
TI  - Clonidine effects on pain evoked SII activity in humans.
AB  - We investigated pain evoked activity in the human secondary sensory cortex (SII)
      following clonidine administration in six healthy volunteers using multi-channel
      magnetoencephalography (MEG). Pain was elicited by electrical shocks applied
      intracutaneously to the fingertip. Subjects rated pain intensity and perceptions
      of tiredness and passiveness by numerical ranking scales. Each subject underwent
      two investigations, one week apart from each other, with clonidine doses of 1.5
      or 3.0microg/kg, administered intravenously in a random order and double-blinded.
      We applied a total number of seven blocks, each consisting of 60 painful stimuli,
      with one adaptation block, one pre-medication block, four post-medication blocks
      and one recovery block at the end of the session. MEG data were analysed by
      dipole reconstruction using CURRY(R) (Neuroscan, Hamburg) software package.
      Cortical activity in the contralateral SII cortex appeared with peak latencies of
      118.5+/-10ms. This activity was significantly reduced by clonidine, in parallel
      with a reduction of pain intensity and enhancement of subjective tiredness and
      passiveness. There was, however, no significant correlation between MEG and
      subjective effects. Although both clonidine doses had similar effects, the higher
      dose induced longer changes. Results indicate that intravenous clonidine is able
      to relieve pain, but the exact mechanism of clonidine at the level of the SII
      cortex remains unclear. It is possible that clonidine interacts with the
      brainstem ascending system regulating vigilance and arousal which would explain
      the observed decrement of pain induced activity in SII. An additional more
      specific analgesic action at spinal level cannot be excluded.

PMID- 16439174
TI  - Complex regional pain syndrome in children and adolescents.
AB  - Complex regional pain syndrome (CRPS) is a disorder characterised by pain,
      sensory and motor disturbances and represents a significant medical entity. This
      report discusses two cases of CRPS in children and adolescents, highlighting
      several critical issues for clinicians in the diagnosis and management of CRPS in
      these populations. Early diagnosis, referral and appropriate intervention are
      essential in decreasing pain, suffering and resorting function for children and
      adolescents with CRPS.

PMID- 16439175
TI  - Impact of cblB mutations on the function of ATP:cob(I)alamin adenosyltransferase
      in disorders of vitamin B12 metabolism.
AB  - ATP:cob(I)alamin adenosyltransferase (MMAB protein; methylmalonic aciduria type
      B) is an enzyme of vitamin B(12) metabolism that converts reduced cob(I)alamin to
      the adenosylcobalamin co-factor required for the functional activity of
      methylmalonyl-CoA mutase. Mutations in the human MMAB gene result in a block in
      adenosylcobalamin synthesis and are responsible for the cblB complementation
      group of inherited vitamin B(12) disorders. In this study, we examined the impact
      of several mutations, previously identified in cblB patients and clustered within
      a small, highly conserved region in MMAB. We confirmed mitochondrial expression
      of MMAB in human cells and showed that two mutations, R186W and E193K, were
      associated with absent protein by Western blot, while one, R191W, coupled with
      another point mutation, produced a protein in patient fibroblasts. Wild type MMAB
      and all four mutant proteins were stably expressed at high level as GST-fusion
      proteins, but only the R191W protein was enzymatically active. It showed an
      elevated K(m) of 320 microM (vs 6.8 microM for wild type enzyme) for ATP and 60
      microM (vs 3.7 microM) for cob(I)alamin, with a reduction in k(cat) for both
      substrates. Circular dichroism spectroscopy revealed that three mutant proteins
      examined retained a alpha-helical structure as for the wild type protein.
      Characterization of MMAB will contribute to our understanding of cobalamin
      processing in mammalian cells and of disease mechanisms in the genetic disorders.

PMID- 16439176
TI  - alpha-L-Iduronidase transport in neurites.
AB  - Effective therapeutic strategies for mucopolysaccharidosis type I (MPSI) rely on
      mannose-6-phosphate receptor-mediated uptake of extracellular alpha-l-iduronidase
      (IDUA), the missing lysosomal enzyme in this disease, by deficient cells.
      Intravenously infused recombinant human IDUA does not reach the central nervous
      system, whereas neuropathology and neurological manifestations are prominent in
      Hurler syndrome, the most severe and most frequent form of MPSI. The creation of
      a single intracerebral source of IDUA by gene therapy was proved efficient to
      deliver enzyme throughout the brain of MPSI mice. IDUA spreading far beyond areas
      where the enzyme was synthesized suggested transport along neuronal processes. To
      examine the mechanisms of IDUA spreading in the brain, we constructed a chimeric
      protein in which GFP is fused at the C-terminus of IDUA. The fusion protein was
      expressed in rat primary neurons using lentivirus vectors. Fluorescent IDUA
      retained full catalytic activity including on natural substrates, interacted with
      mannose-6-phosphate receptors and was appropriately addressed to lysosomes.
      Fluorescent vesicles were broadly distributed over neuronal soma and processes.
      Time-lapse fluorescent video-microscopy showed that 54% of fluorescent vesicles
      exhibited either retrograde or anterograde displacements along neurites. Most
      moving organelles showed complex movements with frequent direction changes and
      arrests. Motility depended on microtubule integrity. Efficient axono-dendritic
      transport of IDUA provides a rationale for gene therapy based on the release of
      therapeutic enzyme at discrete locations within the central nervous system of
      patients with severe form of MPSI.

PMID- 16439177
TI  - The spectrum of Gram-positive bloodstream infections in patients with hematologic
      malignancies, and the in vitro activity of various quinolones against Gram
      positive bacteria isolated from cancer patients.
AB  - OBJECTIVES: To determine the current spectrum of Gram-positive bloodstream
      infections (BSI) in patients with hematologic malignancies at our institution,
      and to determine the in vitro activity of various fluoroquinolones against
      clinical Gram-positive isolates collected from such patients. METHODS:
      Institutional microbiology records from 493 consecutive episodes of Gram-positive
      BSI were reviewed. The in vitro activity of six fluoroquinolones against 477
      clinical isolates was determined using an NCCLS approved, broth-dilution method.
      RESULTS: The most common Gram-positive organisms isolated from the bloodstream of
      patients with hematological malignancies were coagulase-negative staphylococci
      (33%), Staphylococcus aureus (15%), viridans group streptococci (10%), and the
      enterococci (8%). Acute leukemias were the most common underlying malignancies,
      and 73% of patients were neutropenic when they developed their BSI. The newer
      generation quinolones--moxifloxacin and gatifloxacin--had the best overall in
      vitro activity against the Gram-positive isolates tested, and were at least 2 to
      8-fold more potent than the early generation quinolones (ofloxacin and
      ciprofloxacin). Of the 477 isolates tested, 405 (85%) were from patients
      receiving quinolone (ciprofloxacin or levofloxacin) prophylaxis. CONCLUSIONS: In
      patients with hematologic malignancies, Gram-positive BSI are caused by a large
      number of bacterial species and many occur despite antimicrobial prophylaxis. The
      newer generation quinolones--moxifloxacin and gatifloxacin--have better in vitro
      activity against these organisms than early generation agents (ciprofloxacin and
      ofloxacin).

PMID- 16439178
TI  - [Prepubic TVT: a longitudinal prospective study of 164 female patients treated
      for stress urinary incontinence. Gynecol Obstet Fertil 2005;33:570-576].

PMID- 16439180
TI  - [For the routine use of misoprostol in induced labour].

PMID- 16439182
TI  - SPASM: a 3D-ASM for segmentation of sparse and arbitrarily oriented cardiac MRI
      data.
AB  - A new technique (SPASM) based on a 3D-ASM is presented for automatic segmentation
      of cardiac MRI image data sets consisting of multiple planes with arbitrary
      orientations, and with large undersampled regions. Model landmark positions are
      updated in a two-stage iterative process. First, landmark positions close to
      intersections with images are updated. Second, the update information is
      propagated to the regions without image information, such that new locations for
      the whole set of the model landmarks are obtained. Feature point detection is
      performed by a fuzzy inference system, based on fuzzy C-means clustering. Model
      parameters were optimized on a computer cluster and the computational load
      distributed by grid computing. SPASM was applied to image data sets with an
      increasing sparsity (from 2 to 11 slices) comprising images with different
      orientations and stemming from different MRI acquisition protocols. Segmentation
      outcomes and calculated volumes were compared to manual segmentation on a dense
      short-axis data configuration in a 3D manner. For all data configurations, (sub
      )pixel accuracy was achieved. Performance differences between data configurations
      were significantly different (p<0.05) for SA data sets with less than 6 slices,
      but not clinically relevant (volume differences<4 ml). Comparison to results from
      other 3D model-based methods showed that SPASM performs comparable to or better
      than these other methods, but SPASM uses considerably less image data.
      Sensitivity to initial model placement proved to be limited within a range of
      position perturbations of approximately 20 mm in all directions.

PMID- 16439181
TI  - The use of ultrasound in the extraction of Ilex paraguariensis leaves: a
      comparison with maceration.
AB  - The objective of this work is to discuss the main parameters that influence the
      sonication extraction of Ilex paraguariensis leaves. For this purpose, the
      extraction time, solvent polarity, solvent volume, sample mass and particle size
      were evaluated. Results showed that the main variable affecting the extraction
      process was the solvent polarity. Though in a less extent, temperature and
      extraction time also demonstrated to be important parameters, while the other
      variables did not present a significant influence on the extraction yield. The
      extracts at the optimized condition were compared with those obtained by
      maceration, in terms of mass yield and chemical composition. The major compounds
      identified in the extracts were caffeine and palmitic acid. Some saturated
      hydrocarbons such as fatty acids, fatty acid methyl esters, phytosterols, and
      theobromine were also identified in the fractions.

PMID- 16439183
TI  - A dual effect of N-acetylcysteine on acute ethanol-induced liver damage in mice.
AB  - Reactive oxygen species (ROS) have been associated with acute ethanol-induced
      liver damage. N-acetylcysteine (NAC) is a glutathione (GSH) precursor and direct
      antioxidant. In this study, we investigated the effects of NAC on acute ethanol
      induced liver damage. Female ICR mice were administered by gavage with a single
      dose of ethanol (6g/kg). NAC was administered in two different modes. In mode A,
      mice were injected with different doses of NAC at 30min before ethanol. In mode
      B, mice were injected with different doses of NAC at 4h after ethanol. Acute
      ethanol-induced liver damage was estimated by measuring serum alanine
      aminotransferase (ALT) activity and histopathological changes. Result showed that
      a single dose of ethanol (6g/kg) caused a significant increase in serum ALT
      activity, followed by microvesicular steatosis and necrosis in mouse liver.
      Pretreatment with NAC significantly protected against acute ethanol-induced liver
      damage in a dose-independent manner. Correspondingly, pretreatment with NAC
      significantly attenuated acute ethanol-induced lipid peroxidation and GSH
      depletion and inhibited hepatic TNF-alpha mRNA expression. By contrast, post
      treatment with NAC aggravated ethanol-induced hepatic lipid peroxidation and
      worsened acute ethanol-induced liver damage in a dose-dependent manner. Taken
      together, NAC has a dual effect on acute ethanol-induced liver damage.
      Pretreatment with NAC prevent from acute ethanol-induced liver damage via
      counteracting ethanol-induced oxidative stress. When administered after ethanol,
      NAC might behave as a pro-oxidant and aggravate acute ethanol-induced liver
      damage.

PMID- 16439184
TI  - Effects of thirty minutes mobile phone use on the human sensory cortex.
AB  - OBJECTIVE: To investigate whether the pulsed high-frequency electromagnetic field
      (pulsed EMF) emitted by a mobile phone for 30 min has short-term effects on human
      somatosensory evoked potentials (SEPs). METHODS: We studied somatosensory evoked
      potentials (SEPs) in 12 normal volunteers before and after exposure to the
      electromagnetic field emitted by a mobile phone for 30 min compared with sham
      exposure. In 7 out of the subjects we also measured the recovery function of the
      SEP. RESULTS: Neither SEPs nor their recovery function was affected by exposure
      to pulsed EMF emitted by a mobile phone or sham phone use. CONCLUSIONS: As far as
      the present methods are concerned, 30 min mobile phone use has no short-term
      effects on the human sensory cortex. SIGNIFICANCE: This is the first study of
      SEPs after electromagnetic exposure by the mobile phone. Our results support the
      safety of the mobile phone.

PMID- 16439185
TI  - Identification of circular codes in bacterial genomes and their use in a
      factorization method for retrieving the reading frames of genes.
AB  - We developed a statistical method that allows each trinucleotide to be associated
      with a unique frame among the three possible ones in a (protein coding) gene. An
      extensive gene study in 175 complete bacterial genomes based on this statistical
      approach resulted in identification of 72 new circular codes. Finding a circular
      code enables an immediate retrieval of the reading frame locally anywhere in a
      gene. No knowledge of location of the start codon is required and a short window
      of only a few nucleotides is sufficient for automatic retrieval. We have
      therefore developed a factorization method (that explores previously found
      circular codes) for retrieving the reading frames of bacterial genes. Its
      principle is new and easy to understand. Neither complex treatment nor specific
      information on the nucleotide sequences is necessary. Moreover, the method can be
      used for short regions in nucleotide sequences (less than 25 nucleotides in
      protein coding genes). Selected additional properties of circular codes and their
      possible biological consequences are also discussed.

PMID- 16439186
TI  - Effects of long-term angiotensin converting enzyme inhibition on cardiovascular
      variability in aging rats.
AB  - We studied the effects of chronic (4 weeks) angiotensin converting enzyme
      inhibition with captopril on arterial pressure (AP) and heart rate (HR)
      variability, as well as on cardiac baroreflex sensitivity (BRS), in aged (20
      months) rats. Series of basal RR interval (RRi) and systolic AP (SAP) were
      studied by autoregressive spectral analysis with oscillations quantified in low
      (LF: 0.2-0.8 Hz) and high frequency (HF: 0.8-2.5 Hz). BRS was measured by linear
      regression between HR and MAP changes. Captopril did not affect the spectra of
      RRi or SAP in young rats. Aged rats presented a reduction in variance (time
      domain) and in LF and HF oscillations of RRi and SAP. Captopril induced, in aged
      rats, a decrease in absolute and normalized LF oscillations and in LF/HF ratio of
      RRi. Captopril also reduced the variance, without changing its LF or HF
      components of SAP. Reflex tachycardia was reduced in aged as compared to young
      rats (-1.1+/-0.2 versus -3.4+/-0.5 bpm/mm Hg) and captopril did not affect it.
      Reflex bradycardia was also reduced in aged rats (-0.7+/-0.5 versus -2.0+/-0.4
      bpm/mm Hg), but captopril prevented this attenuation in aged rats (-2.3+/-0.3
      versus -0.7+/-0.5 bpm/mm Hg). These data indicate that there is a reduction in HR
      and SAP variability during aging, suggesting impairment of cardiovascular
      autonomic control. Captopril was able to change the power of oscillatory
      components of RRi, suggesting a shift in cardiac sympatho/vagal balance toward
      parasympathetic predominance. In addition, blockage of ACE improved the reflex
      bradycardia, but not the reflex tachycardia in aged rats.

PMID- 16439187
TI  - Determination of tetrodotoxin in human urine and blood using C18 cartridge
      column, ultrafiltration and LC-MS.
AB  - Six fishermen were victims (including one death) of food poisoning from unknown
      fish on their boat in central Taiwan Strait, in April 2001. The symptoms were
      like those of tetrodotoxin (TTX) poisoning. As there was no remaining fish, a new
      protocol was developed to determine TTX in the urine and blood of the victims.
      The urine and blood samples were cleansed using a C18 Sep-Pak cartridge column,
      and the toxin was extracted by methanol. The eluate was filtered through a
      microcentrifuge filter. The filtrate was freeze-dried, dissolved in distilled
      water, and determined by LC-MS. The recovery was more than 88.9%. The detection
      limit was 15.6 nM. A linear relationship between response and concentration was
      obtained between 93.75 and 9375 nM of TTX. It was shown that the urine and blood
      of the victims contained TTX. The range of TTX was 4.5-40.6 nM in blood and 47
      344 nM in urine. Judging from the symptoms of the victims and the experimental
      data, the causative agent of the food poisoning was identified as TTX.

PMID- 16439188
TI  - New method for HPLC separation and fluorescence detection of malonaldehyde in
      normal human plasma.
AB  - A new method for the detection of free and total malonaldehyde (MDA) in human
      plasma samples based on the derivatization of MDA with 9-fluorenylmethoxycarbonyl
      hydrazine (FMOC-hydrazine) in an acidic medium was developed. Derivatization was
      achieved after 4 h at 50 degrees C. The derivatized samples were analyzed by HPLC
      using a reversed-phase C18 column with fluorescence detection (Ex=270 nm, Em=310
      nm). The benefit of this direct injection of deproteinized plasma is to avoid the
      use of an internal standard. The detection limit was 0.1 pmol (4.0 nmol/L). The
      recovery of MDA spiked in different human plasma samples was 95.3% (n=25; R.S.D.
      5.1%) for the hydrolysation procedure. The total and free MDA in plasma of 15
      healthy male volunteers are 426+/-29.8 nmol/L and 153+/-9.6 nmol/L, respectively.

PMID- 16439189
TI  - Twin differences in birth weight: the effects of genotype and prenatal
      environment on neonatal and post-neonatal mortality.
AB  - There is much evidence to suggest that both genes and prenatal environment
      influence life chances. However, recent within-twin estimates also raise
      questions about how the influence of genes and prenatal environment may vary
      across different subgroups of a population and over time. This paper explores
      such potential variation within the 1st year of life. Using data on twin births
      from the 1995-1997 Matched Multiple Birth Database and an analytic strategy based
      on the Weinberg assumption, this paper considers how associations between birth
      weight and infant mortality vary across identical and fraternal twins,
      gestational age, and time. Results suggest that the influence of genes and
      prenatal environment vary most significantly by gestational age. In pregnancies
      that lasted less than 37 weeks, within-twin variation in prenatal environment is
      able to account for negative associations between birth weight and infant
      mortality. However, in pregnancies that lasted 37 weeks or longer, underlying
      genetic variation across fraternal twins appears to be largely responsible for
      birth weight-mortality associations. Such distinct findings by gestation suggest
      that genes and prenatal environment may play varying roles in birth weight
      mortality associations across different situations.

PMID- 16439190
TI  - The happy Scandinavian celiac world.

PMID- 16439191
TI  - Strontium ranelate: a physiological approach for optimizing bone formation and
      resorption.
AB  - Osteoporosis associated with estrogen deficiency results from an imbalance
      between bone resorption and formation, causing deterioration of bone architecture
      and decreased bone mass. Anti-osteoporotic therapies that have been developed so
      far include either anticatabolic or anabolic drugs. Strontium ranelate is a newly
      developed drug that induces opposite effects on bone resorption and formation.
      This dual original mode of action was demonstrated in experimental studies on
      bone cells and pharmacological studies in animals. In vitro, strontium ranelate
      was shown to decrease bone resorption. This effect resulted from a decreased
      differentiation and resorbing activity of osteoclasts and increased osteoclast
      apoptosis. In contrast, strontium ranelate was shown to enhance preosteoblastic
      cell replication and collagen synthesis in culture without affecting bone
      mineralization. In vivo, strontium ranelate promoted bone formation and reduced
      bone resorption in intact mice, an effect which resulted in increased vertebral
      bone mass. Additionally, strontium ranelate was found to reduce resorption and
      long bone loss induced by hind limb immobilization in rats. Finally, strontium
      ranelate administration decreased bone resorption and maintained bone formation
      in adult ovariectomized rats, which resulted in prevention of bone loss. In
      clinical trials (Spinal Osteoporosis Therapeutic Intervention [SOTI]), bone
      alkaline phosphatase levels increased, whereas C cross-linking telopeptide of
      type I collagen (CTX) levels decreased in patients treated with strontium
      ranelate compared with placebo at all time points. These pharmacological and
      clinical studies suggest that strontium ranelate acts by increasing bone
      formation and decreasing bone resorption and that these effects result in
      improved bone mass in vivo.

PMID- 16439192
TI  - A fetching model organism.
AB  - The creation of the domestic dog and its many breeds has been an ongoing
      experiment in the rapid evolution of form and function. Now, advances in genomics
      have made Canis familiaris genetically tractable and poised to offer insights
      into evolution, development, and behavior.

PMID- 16439193
TI  - A colorful model of the circadian clock.
AB  - The migration of the colorful monarch butterfly provides biologists with a unique
      model system with which to study the cellular and molecular mechanisms underlying
      a sophisticated circadian clock. The monarch circadian clock is involved in the
      induction of the migratory state and navigation over long distances, using the
      sun as a compass.

PMID- 16439194
TI  - Small brains, bright minds.
AB  - Learning, memory, and social behavior are innate properties of the honeybee that
      are essential for the survival of each individual as well as for the survival of
      the hive. The small, accessible brain of the honeybee and the availability of the
      complete sequence of its genome make this social insect an ideal model for
      studying the connection between learning, memory, and social behavior.

PMID- 16439195
TI  - Planarian regeneration: its end is its beginning.
AB  - Why does regeneration take place in some animals but not others? Increased
      understanding of gene function is required to dissect the genetics, cell biology,
      and physiological aspects that make regeneration possible. An unlikely model
      animal, the planarian Schmidtea mediterranea, is proving valuable in this
      endeavor.

PMID- 16439196
TI  - Linking chordate gene networks to cellular behavior in ascidians.
AB  - Embryos of simple chordates called ascidians (sea squirts) have few cells,
      develop rapidly, and are transparent, enabling the in vivo fluorescent imaging of
      labeled cell lineages. Ascidians are also simple genetically, with limited
      redundancy and compact regulatory regions. This cellular and genetic simplicity
      is now being exploited to link comprehensive gene networks to the cellular events
      underlying morphogenesis.

PMID- 16439197
TI  - A greedy promoter controls malarial var-iations.
AB  - Immune evasion by the malaria parasite Plasmodium falciparum is mediated by the
      mutually exclusive expression of a single member of the var family of genes,
      which encode variant surface antigens. In a recent paper in Nature, demonstrate
      that a construct carrying a transcriptionally active var promoter is sufficient
      to promote allelic exclusion of the parasite's endogenous var gene.

PMID- 16439198
TI  - Nervous activity in a stem cell niche.
AB  - In this issue of Cell, report a new regulatory axis for the mobilization of
      hematopoietic stem cells that links these cells to the nervous system and bone in
      an unanticipated way. The new findings suggest that the nervous system, which has
      the inherent ability to integrate information from throughout the organism, may
      govern the local relationship between stem cells and their niches.

PMID- 16439199
TI  - REGgamma: a shortcut to destruction.
AB  - Destruction of intact cellular proteins is largely orchestrated by ATP-dependent
      ubiquitination and subsequent degradation by the 26S proteasome. The REG-20S
      proteasome, however, only degrades short peptides. In this issue of Cell,
      challenge this notion by revealing that the proteasomal activator REGgamma
      directs degradation of the steroid receptor coactivator SRC-3 by the 20S
      proteasome in an ATP- and ubiquitin-independent manner.

PMID- 16439200
TI  - Methylglyoxal comes of AGE.
AB  - The posttranslational modification of proteins by methylglyoxal, a highly
      reactive compound derived from glycolysis, may contribute to aging, diabetes, and
      other disorders. In this issue of Cell, Brownlee and colleagues (Yao et al.,
      2006) demonstrate a specific mechanism by which methylglyoxal modifies a
      transcriptional corepressor to enhance gene expression.

PMID- 16439201
TI  - DNA double-strand break repair: a relentless hunt uncovers new prey.
AB  - A major pathway for repair of DNA double-strand breaks is nonhomologous end
      joining (NHEJ). In this issue of Cell, and report the discovery of a new NHEJ
      factor called Cernunnos-XLF. Both groups report that this protein is mutated in a
      rare inherited human syndrome characterized by severe immunodeficiency,
      developmental delay, and hypersensitivity to agents that cause DNA double-strand
      breaks.

PMID- 16439202
TI  - Macrophages: obligate partners for tumor cell migration, invasion, and
      metastasis.
AB  - Macrophages within the tumor microenvironment facilitate angiogenesis and
      extracellular-matrix breakdown and remodeling and promote tumor cell motility.
      Recent studies reveal that direct communication between macrophages and tumor
      cells leads to invasion and egress of tumor cells into the blood vessels
      (intravasation). Thus, macrophages are at the center of the invasion
      microenvironment and are an important drug target for cancer therapy.

PMID- 16439203
TI  - From cell structure to transcription: Hippo forges a new path.
AB  - The control of cell number during animal development is a longstanding puzzle.
      Recent studies in the fruit fly Drosophila melanogaster have defined a new
      signaling pathway that restricts cell proliferation in differentiating epithelia.
      The cytoskeletal proteins Merlin and Expanded, which play a role in cell adhesion
      and structure, control the activation of the Hippo/Salvador kinase complex, which
      in turn activates the Warts/Mats kinase complex. Warts/Mats kinase phosphorylates
      and inhibits Yorkie, a transcriptional coactivator that positively regulates cell
      growth, survival, and proliferation. This conserved signaling pathway contains
      several tumor-suppressor genes and regulates the contact inhibition of
      proliferation in cultured cells.

PMID- 16439204
TI  - Cernunnos, a novel nonhomologous end-joining factor, is mutated in human
      immunodeficiency with microcephaly.
AB  - DNA double-strand breaks (DSBs) occur at random upon genotoxic stresses and
      represent obligatory intermediates during physiological DNA rearrangement events
      such as the V(D)J recombination in the immune system. DSBs, which are among the
      most toxic DNA lesions, are preferentially repaired by the nonhomologous end
      joining (NHEJ) pathway in higher eukaryotes. Failure to properly repair DSBs
      results in genetic instability, developmental delay, and various forms of
      immunodeficiency. Here we describe five patients with growth retardation,
      microcephaly, and immunodeficiency characterized by a profound T+B
      lymphocytopenia. An increased cellular sensitivity to ionizing radiation, a
      defective V(D)J recombination, and an impaired DNA-end ligation process both in
      vivo and in vitro are indicative of a general DNA repair defect in these
      patients. All five patients carry mutations in the Cernunnos gene, which was
      identified through cDNA functional complementation cloning. Cernunnos/XLF
      represents a novel DNA repair factor essential for the NHEJ pathway.

PMID- 16439205
TI  - XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous
      end-joining.
AB  - DNA nonhomologous end-joining (NHEJ) is a predominant pathway of DNA double
      strand break repair in mammalian cells, and defects in it cause radiosensitivity
      at the cellular and whole-organism levels. Central to NHEJ is the protein complex
      containing DNA Ligase IV and XRCC4. By searching for additional XRCC4-interacting
      factors, we identified a previously uncharacterized 33 kDa protein, XRCC4-like
      factor (XLF, also named Cernunnos), that has weak sequence homology with XRCC4
      and is predicted to display structural similarity to XRCC4. We show that XLF
      directly interacts with the XRCC4-Ligase IV complex in vitro and in vivo and that
      siRNA-mediated downregulation of XLF in human cell lines leads to
      radiosensitivity and impaired NHEJ. Furthermore, we establish that NHEJ-deficient
      2BN cells derived from a radiosensitive and immune-deficient patient lack XLF due
      to an inactivating frameshift mutation in its gene, and that reintroduction of
      wild-type XLF into such cells corrects their radiosensitivity and NHEJ defects.
      XLF thus constitutes a novel core component of the mammalian NHEJ apparatus.

PMID- 16439206
TI  - Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.
AB  - The Sir2 histone deacetylase functions as a chromatin silencer to regulate
      recombination, genomic stability, and aging in budding yeast. Seven mammalian
      Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that
      some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a
      nuclear, chromatin-associated protein that promotes resistance to DNA damage and
      suppresses genomic instability in mouse cells, in association with a role in base
      excision repair (BER). SIRT6-deficient mice are small and at 2-3 weeks of age
      develop abnormalities that include profound lymphopenia, loss of subcutaneous
      fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4
      weeks. We conclude that one function of SIRT6 is to promote normal DNA repair,
      and that SIRT6 loss leads to abnormalities in mice that overlap with aging
      associated degenerative processes.

PMID- 16439207
TI  - Structural analysis of strand misalignment during DNA synthesis by a human DNA
      polymerase.
AB  - Insertions and deletions in coding sequences can alter the reading frame of genes
      and have profound biological consequences. In 1966, Streisinger proposed that
      these mutations result from strand slippage, which in repetitive sequences
      generates misaligned intermediates stabilized by correct base pairing that
      support polymerization. We report here crystal structures of human DNA polymerase
      lambda, which frequently generates deletion mutations, bound to such
      intermediates. Each contains an extrahelical template nucleotide upstream of the
      active site. Surprisingly, the extra nucleotide, even when combined with an
      adjacent mismatch, does not perturb polymerase active site geometry, which is
      indistinguishable from that for correctly aligned strands. These structures
      reveal how pol lambda can polymerize on substrates with minimal homology during
      repair of double-strand breaks and represent strand-slippage intermediates
      consistent with Streisinger's classical hypothesis. They are thus relevant to the
      origin of single-base deletions, a class of mutations that can confer strong
      biological phenotypes.

PMID- 16439208
TI  - Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in
      multiple small-RNA-mediated pathways.
AB  - In plants, animals, and fungi, members of the Dicer family of RNase III-related
      enzymes process double-stranded RNA (dsRNA) to initiate small-RNA-mediated gene
      silencing mechanisms. To learn how C. elegans Dicer, DCR-1, functions in multiple
      distinct silencing mechanisms, we used a mass-spectrometry-based proteomics
      approach to identify DCR-1-interacting proteins. We then generated and
      characterized deletion alleles for the corresponding genes. The interactors are
      required for production of three species of small RNA, including (1) small
      interfering RNAs (siRNAs), derived from exogenous dsRNA triggers (exo-siRNAs);
      (2) siRNAs derived from endogenous triggers (endo-siRNAs); and (3) developmental
      regulatory microRNAs (miRNAs). One interactor, the conserved RNA-phosphatase
      homolog PIR-1, is required for the processing of a putative amplified DCR-1
      substrate. Interactors required for endo-siRNA production include ERI-1 and RRF
      3, whose loss of function enhances RNAi. Our findings provide a first glimpse at
      the complex biochemical niche of Dicer and suggest that competition exists
      between DCR-1-mediated small-RNA pathways.

PMID- 16439209
TI  - Structural insight into the mechanism of double-stranded RNA processing by
      ribonuclease III.
AB  - Members of the ribonuclease III (RNase III) family are double-stranded RNA
      (dsRNA) specific endoribonucleases characterized by a signature motif in their
      active centers and a two-base 3' overhang in their products. While Dicer, which
      produces small interfering RNAs, is currently the focus of intense interest, the
      structurally simpler bacterial RNase III serves as a paradigm for the entire
      family. Here, we present the crystal structure of an RNase III-product complex,
      the first catalytic complex observed for the family. A 7 residue linker within
      the protein facilitates induced fit in protein-RNA recognition. A pattern of
      protein-RNA interactions, defined by four RNA binding motifs in RNase III and
      three protein-interacting boxes in dsRNA, is responsible for substrate
      specificity, while conserved amino acid residues and divalent cations are
      responsible for scissile-bond cleavage. The structure reveals a wealth of
      information about the mechanism of RNA hydrolysis that can be extrapolated to
      other RNase III family members.

PMID- 16439210
TI  - The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase
      promoting complex inhibitor emi1.
AB  - The anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 controls
      progression to S phase and mitosis by stabilizing key APC/C ubiquitination
      substrates, including cyclin A. Examining Emi1 binding proteins, we identified
      the Evi5 oncogene as a regulator of Emi1 accumulation. Evi5 antagonizes
      SCF(betaTrCP)-dependent Emi1 ubiquitination and destruction by binding to a site
      adjacent to Emi1's DSGxxS degron and blocking both degron phosphorylation by Polo
      like kinases and subsequent betaTrCP binding. Thus, Evi5 functions as a
      stabilizing factor maintaining Emi1 levels in S/G2 phase. Evi5 protein
      accumulates in early G1 following Plk1 destruction and is degraded in a Plk1- and
      ubiquitin-dependent manner in early mitosis. Ablation of Evi5 induces precocious
      degradation of Emi1 by the Plk/SCF(betaTrCP) pathway, causing premature APC/C
      activation; cyclin destruction; cell-cycle arrest; centrosome overduplication;
      and, finally, mitotic catastrophe. We propose that the balance of Evi5 and Polo
      like kinase activities determines the timely accumulation of Emi1 and cyclin,
      ensuring mitotic fidelity.

PMID- 16439211
TI  - The SRC-3/AIB1 coactivator is degraded in a ubiquitin- and ATP-independent manner
      by the REGgamma proteasome.
AB  - Steroid receptor coactivator-3 (SRC-3/AIB1) is an oncogene frequently amplified
      and overexpressed in breast cancers. Here we report that SRC-3 interacts with
      REGgamma, a proteasome activator known to stimulate the trypsin-like activity of
      the 20S proteasome. RNAi knockdown and gain-of-function experiments suggest that
      REGgamma promotes SRC-3 protein degradation. Cellular levels of REGgamma
      expression affect estrogen-receptor target-gene expression and cell growth as a
      result of its ability to promote degradation of the SRC-3 protein. In vitro
      proteasome proteolysis assays using purified REGgamma, SRC-3, and the 20S
      proteasome reinforce these conclusions and demonstrate that REGgamma promotes the
      degradation of SRC-3 in a ubiquitin- and ATP-independent manner. This work
      demonstrates the first example of a physiologically relevant endogenous cellular
      target for the REGgamma-proteasome complex. It also highlights the fact that an
      alternative mode of proteasome-mediated protein degradation, independent of the
      19S proteasome regulatory cap, targets the SRC-3 protein for degradation.

PMID- 16439212
TI  - Identification of intrinsic determinants of midbrain dopamine neurons.
AB  - The prospect of using cell replacement therapies has raised the key issue of
      whether elucidation of developmental pathways can facilitate the generation of
      therapeutically important cell types from stem cells. Here we show that the
      homeodomain proteins Lmx1a and Msx1 function as determinants of midbrain dopamine
      neurons, cells that degenerate in patients with Parkinson's disease. Lmx1a is
      sufficient and required to trigger dopamine cell differentiation. An early
      activity of Lmx1a is to induce the expression of Msx1, which complements Lmx1a by
      inducing the proneural protein Ngn2 and neuronal differentiation. Importantly,
      expression of Lmx1a in embryonic stem cells results in a robust generation of
      dopamine neurons with a "correct" midbrain identity. These data establish that
      Lmx1a and Msx1 are critical intrinsic dopamine-neuron determinants in vivo and
      suggest that they may be essential tools in cell replacement strategies in
      Parkinson's disease.

PMID- 16439213
TI  - Signals from the sympathetic nervous system regulate hematopoietic stem cell
      egress from bone marrow.
AB  - Hematopoietic stem and progenitor cells (HSPC), attracted by the chemokine
      CXCL12, reside in specific niches in the bone marrow (BM). HSPC migration out of
      the BM is a critical process that underlies modern clinical stem cell
      transplantation. Here we demonstrate that enforced HSPC egress from BM niches
      depends critically on the nervous system. UDP-galactose ceramide
      galactosyltransferase-deficient (Cgt(-/-)) mice exhibit aberrant nerve conduction
      and display virtually no HSPC egress from BM following granulocyte colony
      stimulating factor (G-CSF) or fucoidan administration. Adrenergic tone,
      osteoblast function, and bone CXCL12 are dysregulated in Cgt(-/-) mice.
      Pharmacological or genetic ablation of adrenergic neurotransmission indicates
      that norepinephrine (NE) signaling controls G-CSF-induced osteoblast suppression,
      bone CXCL12 downregulation, and HSPC mobilization. Further, administration of a
      beta(2) adrenergic agonist enhances mobilization in both control and NE-deficient
      mice. Thus, these results indicate that the sympathetic nervous system regulates
      the attraction of stem cells to their niche.

PMID- 16439214
TI  - Control of the assembly of ATP- and ADP-actin by formins and profilin.
AB  - Formin proteins nucleate actin filaments, remaining processively associated with
      the fast-growing barbed ends. Although formins possess common features, the
      diversity of functions and biochemical activities raised the possibility that
      formins differ in fundamental ways. Further, a recent study suggested that
      profilin and ATP hydrolysis are both required for processive elongation mediated
      by the formin mDia1. We used total internal reflection fluorescence microscopy to
      observe directly individual actin filament polymerization in the presence of two
      mammalian formins (mDia1 and mDia2) and two yeast formins (Bni1p and Cdc12p). We
      show that these diverse formins have the same basic properties: movement is
      processive in the absence or presence of profilin; profilin accelerates
      elongation; and actin ATP hydrolysis is not required for processivity. These
      results suggest that diverse formins are mechanistically similar, but the rates
      of particular assembly steps vary.

PMID- 16439215
TI  - Expanding the use of Microsoft PowerPoint. An overview for radiologists.
AB  - Most radiologists need to give a lecture, present research or speak at a
      scientific meeting at some stage in their career. In our technologically advanced
      world, electronic presentations have become the norm and are almost universally
      expected. Microsoft PowerPoint is by far and away the most commonly used computer
      based presentation package. As a result most radiologists have developed at least
      a modicum of PowerPoint expertise but many lack the time or inclination to
      develop these skills further. The purpose of this article is to explain how to
      expand the use of PowerPoint with freely available resources from the internet,
      to highlight websites where useful information on advanced PowerPoint techniques
      can be found, and to discuss extended functions of PowerPoint likely to be of
      interest to radiologists such as poster design.

PMID- 16439217
TI  - Minimal preparation CT for the diagnosis of suspected colorectal cancer in the
      frail and elderly patient.
AB  - Colorectal cancer is a common malignancy with an increased incidence in the
      elderly population. Traditional methods of evaluating this disease have included
      double contrast barium enema and colonoscopy. Unfortunately, in the frail and
      elderly patient, these investigations can be difficult to perform and are often
      not tolerated. Minimal preparation computed tomography (MPCT) of the colon has
      been suggested as an alternative in this patient population. In this technique,
      no bowel preparation is used apart from the administration of oral contrast
      medium. The patient is imaged only in the supine position, without per rectal
      insufflation of gas or barium. This article reviews the experience to date of
      MPCT in detecting colonic tumours, and compares its efficacy to the traditional
      methods. A meta-analysis of the studies allowed estimation of the pooled
      sensitivity of MPCT to be 83% (95% confidence interval: 76-89%), and pooled
      specificity to be 90% (95% CI: 85-94%). An added advantage of MPCT is the ability
      to identify extra-colonic pathology, and this aspect is also reviewed. In
      addition, the common radiological features and pitfalls in identifying colonic
      tumours by MPCT are discussed.

PMID- 16439218
TI  - Ultrasound-guided prostate biopsy in 2005.

PMID- 16439219
TI  - Current status of transrectal ultrasound-guided prostate biopsy in the diagnosis
      of prostate cancer.
AB  - In contemporary practice, most prostate cancers are either invisible on
      ultrasound or indistinguishable from concurrent benign prostatic hyperplasia.
      Diagnosis therefore rests on prostate biopsy. Biopsies are not simply directed at
      ultrasonically visible lesions, as these would miss many cancers; rather the
      whole gland is sampled. The sampling itself is systematic, using patterns based
      on prostate zonal anatomy and the geographical distribution and frequency of
      cancer. This review explains the evolution of the prostate biopsy technique, from
      the classical sextant biopsy method to the more recent extended biopsy protocols
      (8, 10, 12, >12 and saturation biopsy protocols). Extended protocols are
      increasingly being used to improve diagnostic accuracy, especially in those
      patients who require repeat biopsy. This trend has been facilitated by the
      ongoing improvement in safety and acceptability of the procedure, particularly
      with the use of antibiotic prophylaxis and local anaesthesia. The technical
      details of these extended protocols are discussed, as are the current data
      regarding procedure-related morbidity and how this may be minimized.

PMID- 16439220
TI  - Acute stroke treatment; who is going to bleed?

PMID- 16439221
TI  - Early CT signs in patients with acute middle cerebral artery occlusion: incidence
      of contrast staining and haemorrhagic transformations after intra-arterial
      reperfusion therapy.
AB  - AIM: To investigate how often early computed tomography (CT) signs are associated
      with blood-brain barrier (BBB) disruption and result in haemorrhagic
      transformations. MATERIALS AND METHODS: Serial CT findings were prospectively
      evaluated in 61 patients with acute middle cerebral artery (MCA) occlusion who
      underwent initial CT examination within 3h of stroke onset and who were treated
      with intra-arterial reperfusion therapy within 6h of stroke onset. Obscuration of
      the margin of the lentiform nucleus and loss of the insular ribbon were evaluated
      as early CT signs in the deep MCA territories. Cortical effacement was also
      evaluated. BBB disruption was defined as contrast medium staining in post
      therapeutic CT just after reperfusion therapy. The relationship between pre
      therapeutic early CT signs and post-therapeutic contrast staining or haemorrhagic
      transformations was investigated. RESULTS: The frequency of early CT signs in the
      deep MCA territories was significantly higher than that of cortical effacement
      (68.9 versus 27.9%). There were significant correlations between pre-therapeutic
      early CT signs and post-therapeutic contrast staining in both the deep and
      superficial MCA territories. Compared with early CT signs in the deep MCA
      territories, cortical effacement had a significantly higher incidence of post
      therapeutic contrast staining (54.8 versus 82.4%). Although not statistically
      significant, cortical effacement tended to develop into haemorrhagic
      transformations. There was no correlation between early CT signs in the deep MCA
      territories and haemorrhagic transformations. CONCLUSION: Cortical effacement may
      be an advanced CT sign with BBB disruption and potential risk for haemorrhagic
      transformations. The presence of early CT signs in the deep MCA territories may
      not be a contraindication of reperfusion therapy.

PMID- 16439222
TI  - Diagnostic accuracy of fracture detection in suspected non-accidental injury: the
      effect of edge enhancement and digital display on observer performance.
AB  - AIM: To compare the effect of varying degrees of edge enhancement and method of
      digital image display on fracture detection in suspected non-accidental injury
      (NAI). MATERIALS AND METHODS: Fifty radiographs from post-mortem skeletal surveys
      in 13 children with suspected NAI were selected. Images were obtained using a
      Fuji 5000R computed radiography system. Hard copies were printed with edge
      enhancement factors 0, 0.5 and 1.2. Images (edge enhancement 0.5) were also
      displayed on a 1K(2) monitor. Six observers independently evaluated all 200
      images for the presence of abnormality. Observers also scored each image for
      visualization of soft tissues, visualization of trabecular markings and overall
      image quality. The paired Student's t-test and location receiver operating curve
      (ROC) analysis were used to compare quality scores and diagnostic accuracy of
      each display method. Individual and pooled true-positive rates (sensitivity) were
      determined. For the purposes of ROC analysis, histology was taken as the gold
      standard. RESULTS: There was no difference in duration of hard and soft-copy
      reading sessions (p=0.76). After image manipulation soft-copy radiographs scored
      significantly better for image quality than hard copy (p<0.0001). Pooled observer
      sensitivity (at a specificity of 90%) was below 50% for all display methods.
      Diagnostic accuracy varied significantly between observers. Diagnostic accuracy
      of individual observers was not affected by display method. CONCLUSION: In
      suspected NAI, diagnostic accuracy of fracture detection is generally low.
      Diagnostic accuracy appears to be affected more by observer-related factors than
      by the method of digital image display.

PMID- 16439223
TI  - Non-invasive detection of significant coronary artery disease with multi-section
      computed tomography angiography in patients with suspected coronary artery
      disease.
AB  - AIM: The objective of this prospective study was to compare the accuracy of multi
      section computed tomography (MSCT) coronary angiography with invasive selective
      coronary angiography in the detection of significant coronary stenosis (> or =50%
      lumen diameter narrowing). METHODS: Thirty consecutive patients (mean age 59+/-10
      years) with suspected coronary artery disease underwent both invasive coronary
      angiography and MSCT using a 40-section multidetector row machine with temporal
      resolution of 53ms. Reconstruction images were performed in eight phases of the
      cardiac cycle. Images of MSCT and invasive coronary angiography were analysed
      using the 16-segment model of the American Heart Association. RESULTS: A total of
      480 segments from 30 patients were evaluated. Coronary segments distal to a
      vessel occlusion and segments with coronary stent were not considered for
      analysis (20 segments in total). Ninety-four (20.4%) segments showed significant
      (> or =50%) stenosis by invasive coronary angiogram. The accuracy of coronary
      MSCT was computed on a per segment basis. Average sensitivity, specificity,
      positive predictive value, and negative predictive value of MSCT were 99, 98, 94,
      and 99%, respectively. CONCLUSION: This study demonstrated that MSCT is as
      reliable as coronary angiography at detecting significant obstructive coronary
      artery disease. In selected groups of patients, it may replace the more invasive
      and potentially more dangerous conventional coronary angiography.

PMID- 16439224
TI  - Magnetic resonance imaging of para-acetabular insufficiency fractures in patients
      with malignancy.
AB  - AIM: To describe the characteristic magnetic resonance imaging (MRI) findings of
      para-acetabular insufficiency fractures in patients with malignancy, and compare
      the MRI appearance of these fractures with that of metastatic bone disease.
      MATERIALS AND METHODS: MRI examinations were reviewed in 16 patients with a known
      malignant tumour and severe hip pain that raised the possibility of local
      recurrence or metastatic disease. Six patients had received pelvic irradiation,
      and three patients were receiving steroid medication. RESULTS: The total number
      of fractures detected was 21: a solitary fracture was present in 11 patients and
      five patients had bilateral para-acetabular fractures. Two patients had
      associated sacral insufficiency fractures, and one of them had stress fractures
      involving both acetabular columns. Conventional radiography allowed the diagnosis
      of 14 (67%) fractures; six (28%) radiographic examinations were negative; and one
      (5%) examination was equivocal for fracture. Available scintigraphic and computed
      tomography (CT) studies revealed typical findings of fracture. Using MRI,
      insufficiency fractures appeared as linear regions of low signal intensity on T1-
      and T2-weighted images. Marked marrow oedema was evident in all cases. Fractures
      characteristically were parallel to the superior acetabulum in a curvilinear
      fashion in 18 (86%) instances, and were oblique in three (14%) instances. The
      fractures demonstrated considerable enhancement after intravenous gadolinium
      administration. No associated soft tissue masses were documented. CONCLUSION:
      Para-acetabular insufficiency fractures are a cause of hip pain, which may mimic
      skeletal metastasis in the patient with malignancy and pelvic irradiation.
      Recognition of the characteristic MRI findings of these fractures can preclude
      misdiagnosis and unnecessary bone biopsy.

PMID- 16439225
TI  - Ultrasonographic detection of hepatocellular carcinoma: correlation of
      preoperative ultrasonography and resected liver pathology.
AB  - AIM: The aim of this study was to determine the sensitivity of ultrasonography
      for detecting hepatocellular carcinoma in patients who underwent surgical liver
      resection. MATERIALS AND METHODS: The preoperative ultrasonography reports of 103
      patients who underwent hepatic resection surgery were retrospectively reviewed.
      The patients had chronic liver disease with good liver function and a relatively
      normal liver echo-texture. The presence of a mass or masses in the resected part
      of the liver segments on preoperative ultrasonography was regarded as possible
      hepatocellular carcinoma, and these results were compared with the surgically
      resected hepatic lobes or segments. Accuracy for detection was assessed on a
      lesion-by-lesion basis, on a segment-by-segment basis, and on a patient basis.
      RESULTS: One hundred and fifty-seven hepatocellular carcinomas were found in 244
      hepatic segments of 103 patients. One hundred and one of 157 hepatocellular
      carcinomas were detected using ultrasonography in 97 patients resulting in a
      sensitivity of 64%. In six patients, a solitary hepatocellular carcinoma was
      missed in each patient, a patient sensitivity being 94%. Using ultrasonography,
      87 of 100 (87%) hepatocellular carcinomas larger than 2 cm in diameter, and 14 of
      57 (25%) hepatocellular carcinomas 2 cm or smaller in diameter were revealed. On
      the basis of segment-by-segment analysis, the sensitivity was 78% (99 of 127
      segments), specificity was 97% (114 of 117 segments), accuracy was 87% (213 of
      244 segments), positive predictive value was 97% (99 of 102 segments), and
      negative predictive value was 80% (114 of 142 segments). CONCLUSION: In patients
      with chronic liver disease and good hepatic function, ultrasonography has a
      sensitivity of 94% in the identification of affected patients, but for individual
      lesions, the sensitivity is only 64%.

PMID- 16439226
TI  - Polypoid endometriosis and other benign gynaecological complications associated
      with Tamoxifen therapy-a case to illustrate features on magnetic resonance
      imaging.

PMID- 16439227
TI  - Endobronchial non-Hodgkin's lymphoma presenting as an isolated endobronchial
      mass.

PMID- 16439228
TI  - Use of a semi-automated left ventricular "rapid ejection fraction" algorithm with
      16-detector row CT and comparison with two-dimensional echocardiography: initial
      experience in a UK centre.

PMID- 16439229
TI  - Distal femoral fractures: a review of fixation methods.
AB  - The treatment of distal femoral fractures has evolved; nevertheless, these
      fractures remain difficult to treat and carry an unpredictable prognosis. Over
      the years, many different strategies have been used with varying success. This
      review outlines the problems presented by distal femoral fractures and the
      results of current surgical techniques.

PMID- 16439231
TI  - Analysis of the mechanical behavior of chondrocytes in unconfined compression
      tests for cyclic loading.
AB  - Experimental evidence indicates that the biosynthetic activity of chondrocytes is
      associated with the mechanical environment. For example, excessive, repetitive
      loading has been found to induce cell death, morphological and cellular damage,
      as seen in degenerative joint disease, while cyclic, physiological-like loading
      has been found to trigger a partial recovery of morphological and ultrastructural
      aspects in osteoarthritic human articular chondrocytes. Mechanical stimuli are
      believed to influence the biosynthetic activity via the deformation of cells.
      However, the in situ deformation of chondrocytes for cyclic loading conditions
      has not been investigated experimentally or theoretically. The purpose of the
      present study was to simulate the mechanical response of chondrocytes to cyclic
      loading in unconfined compression tests using a finite element model. The
      material properties of chondrocytes and extracellular matrix were considered to
      be biphasic. The time-histories of the shape and volume variations of
      chondrocytes at three locations (i.e., surface, center, and bottom) within the
      cartilage were predicted for static and cyclic loading conditions at two
      frequencies (0.02 and 0.1 Hz) and two amplitudes (0.1 and 0.2 MPa). Our results
      show that cells at different depths within the cartilage deform differently
      during cyclic loading, and that the depth dependence of cell deformation is
      influenced by the amplitude of the cyclic loading. Cell deformations under cyclic
      loading of 0.02 Hz were found to be similar to those at 0.1 Hz. We conclude from
      the simulation results that, in homogeneous cartilage layers, cell deformations
      are location-dependent, and further are affected by load magnitude. In
      physiological conditions, the mechanical environment of cells are even more
      complex due to the anisotropy, depth-dependent inhomogeneity, and tension
      compression non-linearity of the cartilage matrix. Therefore, it is feasible to
      speculate that biosynthetic responses of chondrocytes to cyclic loading depend on
      cell location and load magnitude.

PMID- 16439230
TI  - Prediction of microdamage formation using a mineral-collagen composite model of
      bone.
AB  - Age-related changes in bone quality are mainly manifested in the reduced
      toughness. Since the post-yield deformation of bone is realized through
      microdamage formation (e.g., microcracking and diffuse damage), it is necessary
      to understand the mechanism of microdamage formation in bone in order to
      elucidate underlying mechanisms of age-related bone fractures. In this study, a
      two-dimensional shear lag model was developed to predict stress concentration
      fields around an initial crack in a mineral-collagen composite. In this model,
      non-linear elasticity was assumed for the collagen phase, and linear elasticity
      for the mineral. Based on the pattern of the stress concentration fields, the
      condition for microdamage formation was discussed. The results of our analyses
      indicate that: (1) an initial crack formed in mineral phase may cause stress
      concentration in the adjacent mineral layers; (2) the pattern of stress
      concentration fields depends not only on the spatial but also mechanical
      properties of the collagen and mineral phases; (3) the pattern of the stress
      concentration fields could determine either coalescence or scattering of nano
      cracks around the initial crack.

PMID- 16439232
TI  - Possible harmful effects of high intra-abdominal pressure on the pelvic girdle.
AB  - The present study explores the hypothesis that a high intra-abdominal pressure
      (IAP) loads the ligaments of the pelvic girdle to such an extent that frequent
      periods of high IAP might cause pain and/or interfere with recovery of patients
      with pelvic girdle pain (PGP). In a theoretical model the size of the load of IAP
      on the pelvic girdle was computed. The diameters of abdomen and pelvis needed for
      the calculations were measured on MRI scans; the IAP values during activities
      were gained from literature. In slim, healthy subjects the calculated load on the
      pelvic ring during activities of daily living was 26.0-52.0 N with peaks to 135
      N. During straining, vigorous work or heavy exercises the load could increase to
      values ranging from 104 to 520 N. The load is higher in subjects with pain or
      fatigue, or in case of a distended abdomen. When the load on the pelvic ring
      induced by IAP is larger than 100 N, the force exceeds the force at which a
      pelvic belt relieves complaints in PGP; at 90 N, the force is larger than the
      force at which isometric hip adduction provokes pain in PGP. We conclude that the
      size of the load induced by IAP on the pelvic girdle seems to be sufficient to
      cause pain in patients with PGP and might interfere with recovery. It seems
      worthwhile to give patients with PGP instructions to reduce IAP as much as
      possible during activities.

PMID- 16439233
TI  - A contact algorithm for density-based load estimation.
AB  - An algorithm, which includes contact interactions within a joint, has been
      developed to estimate the dominant loading patterns in joints based on the
      density distribution of bone. The algorithm is applied to the proximal femur of a
      chimpanzee, gorilla and grizzly bear and is compared to the results obtained in a
      companion paper that uses a non-contact (linear) version of the density-based
      load estimation method. Results from the contact algorithm are consistent with
      those from the linear method. While the contact algorithm is substantially more
      complex than the linear method, it has some added benefits. First, since contact
      between the two interacting surfaces is incorporated into the load estimation
      method, the pressure distributions selected by the method are more likely
      indicative of those found in vivo. Thus, the pressure distributions predicted by
      the algorithm are more consistent with the in vivo loads that were responsible
      for producing the given distribution of bone density. Additionally, the relative
      positions of the interacting bones are known for each pressure distribution
      selected by the algorithm. This should allow the pressure distributions to be
      related to specific types of activities. The ultimate goal is to develop a
      technique that can predict dominant joint loading patterns and relate these
      loading patterns to specific types of locomotion and/or activities.

PMID- 16439234
TI  - Soft tissue vibrations within one soft tissue compartment.
AB  - The concept of muscle tuning suggests that vibrations of the soft tissue
      compartments of the leg initiated by impacts are minimized by muscular activity
      prior to heel-strike of heel-toe running. For the quantification of muscle tuning
      it has been assumed (1) that the soft tissue compartment acts as one lumped mass
      and (2) that vibration energy dissipation does occur within one muscle. The
      purpose of this study was to test these two assumptions. It was hypothesized that
      (H1) the movement of the soft tissue compartment is not homogeneous, (H2) the
      vibration frequencies for different muscles within one soft tissue compartment
      are different and (3) attenuation of vibration movement within one muscle does
      occur. Soft tissue vibrations were measured using accelerometers on four
      locations on the quadriceps soft tissue compartment during heel-toe running.
      There were differences in the peak soft tissue acceleration and time of peak
      acceleration between accelerometer locations. The dominant frequency was similar
      throughout the soft tissue compartment, however; there was an attenuation of high
      frequency vibration energy between distal and proximal points overlying one
      muscle. This evidence suggests that accelerometer placement is important when
      quantifying the acceleration magnitude and timing of peak soft tissue compartment
      but not when estimating the resonant vibration characteristics of a soft tissue
      compartment. It also provides initial evidence to support the idea that vibration
      control through muscle tuning may be achieved through changes in energy
      dissipating properties within the soft tissue compartment.

PMID- 16439235
TI  - A model of non-uniform lung parenchyma distortion.
AB  - A finite element model of mammalian lung parenchyma is used to study the effect
      of large non-uniform distortions on lung elastic behaviour. The non-uniform
      distortion is a uni-axial stretch from an initial state of uniform pressure
      expansion. For small distortions, the parenchymal properties are linearly
      isotropic and described by two elastic moduli. However, for large distortions,
      the parenchyma has anisotropic non-linear elastic properties described by five
      independent elastic moduli dependent on the degree of distortion; they are
      computed for a range of distortions and initial pressures. Ez, the Young's
      modulus in the direction of stretch, increases significantly with distortion
      (epsilon(z)) while Ex, the Young's modulus in the plane perpendicular to the
      stretch, is approximately constant. The greater the initial pressure, the bigger
      the difference between the two moduli at larger distortion strains. The shear
      modulus G(xz) is approximately independent of degree of distortion except at the
      highest initial pressure. The Poisson's ratio, nu(xz) is approximately constant
      with distortion strain for lower initial pressures, but increases significantly
      with epsilon(z) at higher pressures. Model predictions of the relation between
      G(xz) and initial uniform inflation pressure show a good correlation with
      reported experimental data for small distortion strains in a range of species.
      The model also exhibits similar behaviour to the experimentally measured uni
      axial large deformations of a tri-axially pre-loaded block of parenchyma (Hoppin
      et al., 1975, Journal of Applied Physiology 39, 742-751).

PMID- 16439236
TI  - Wave drag on human swimmers.
AB  - Drag measurements from a towed mannequin show total drag at the surface is up to
      2.4 times the drag when fully immersed. This additional drag is due to the energy
      required to form waves in the wake behind the mannequin. The measurements show
      that passive wave drag is the largest drag, comprising up to 50-60% of the total
      at 1.7 m s(-1), much higher than any previous estimates. Comprehensive
      measurements spanning human swimming speeds and tow depths up to 1.0m demonstrate
      that wave drag on the mannequin is less than 5% of total drag for tows deeper
      than 0.5 m at 1 m s(-1) and 0.7 m at 2 m s(-1). Wave drag sharply increases above
      these depths to a maximum of up to 60% of the mannequin's 100 N total drag when
      towed at the surface at 1.7 m s(-1). The measurements show that to avoid
      significant wave drag during the underwater sections of starts and turns,
      swimmers must streamline at depths greater than 1.8 chest depths below the
      surface at Froude number (Fr)=0.2, and 2.8 chest depths at Fr=0.42. This
      corresponds to speeds of 0.9 and 2.0 m s(-1), respectively, for a chest depth of
      0.25 m and toe to finger length of 2.34 m.

PMID- 16439237
TI  - An upper extremity kinematic model for evaluation of hemiparetic stroke.
AB  - Quantification of rehabilitation progress is necessary for accurately assessing
      clinical treatments. A three-dimension (3D) upper extremity (UE) kinematic model
      was developed to obtain joint angles of the trunk, shoulder and elbow using a
      Vicon motion analysis system. Strict evaluation confirmed the system's accuracy
      and precision. As an example of application, the model was used to evaluate the
      upper extremity movement of eight hemiparetic stroke patients with spasticity,
      while completing a set of reaching tasks. Main outcome measures include kinematic
      variables of movement time, range of motion, peak angular velocity, and
      percentage of reach where peak velocity occurs. The model computed motion
      patterns in the affected and unaffected arms. The unaffected arm showed a larger
      range of motion and higher angular velocity than the affected arm. Frequency
      analysis (power spectrum) demonstrated lower frequency content for elbow angle
      and angular velocity in the affected limb when compared to the unaffected limb.
      The model can accurately quantify UE arm motion, which may aid in the assessment
      and planning of stroke rehabilitation, and help to shorten recovery time.

PMID- 16439238
TI  - Kinematic and kinetic factors that correlate with improved knee flexion following
      treatment for stiff-knee gait.
AB  - Stiff-knee gait is a movement abnormality in which knee flexion during swing
      phase is significantly diminished. This study investigates the relationships
      between knee flexion velocity at toe-off, joint moments during swing phase and
      double support, and improvements in stiff-knee gait following rectus femoris
      transfer surgery in subjects with cerebral palsy. Forty subjects who underwent a
      rectus femoris transfer were categorized as "stiff" or "not-stiff" preoperatively
      based on kinematic measures of knee motion during walking. Subjects classified as
      stiff were further categorized as having "good" or "poor" outcomes based on
      whether their swing-phase knee flexion improved substantially after surgery. We
      hypothesized that subjects with stiff-knee gait would exhibit abnormal joint
      moments in swing phase and/or diminished knee flexion velocity at toe-off, and
      that subjects with diminished knee flexion velocity at toe-off would exhibit
      abnormal joint moments during double support. We further hypothesized that
      subjects classified as having a good outcome would exhibit postoperative
      improvements in these factors. Subjects classified as stiff tended to exhibit
      abnormally low knee flexion velocities at toe-off (p<0.001) and excessive knee
      extension moments during double support (p=0.001). Subjects in the good outcome
      group on average showed substantial improvement in these factors postoperatively.
      All eight subjects in this group walked with normal knee flexion velocity at toe
      off postoperatively and only two walked with excessive knee extension moments in
      double support. By contrast, all 10 of the poor outcome subjects walked with low
      knee flexion velocity at toe-off postoperatively and seven walked with excessive
      knee extension moments in double support. Our analyses suggest that improvements
      in stiff-knee gait are associated with sufficient increases in knee flexion
      velocity at toe-off and corresponding decreases in excessive knee extension
      moments during double support. Therefore, while stiff-knee gait manifests during
      the swing phase of the gait cycle, it may be caused by abnormal muscle activity
      during stance.

PMID- 16439239
TI  - Influence of figure skating skates on vertical jumping performance.
AB  - The purpose of this study was to investigate the influence of wearing figure
      skating skates on vertical jump performance and interjoint co-ordinations
      described in terms of sequencing and timing of joint rotations. Ten national to
      international figure skaters were filmed while performing a squat jump (SJ) on a
      force platform. Three experimental conditions were successively realized:
      barefoot (BF), lifting a 1.5 kg weight (LW) corresponding to the skates' mass,
      attached on the distal extremity of each leg and wearing skates (SK). Jump
      height, angular kinematics as well as joints kinetics were calculated. Relative
      to the SJ height reached in the BF condition, SJ performance was significantly
      decreased by 2.1 and 5.5 cm in the LW and SK conditions, respectively. The
      restriction of ankle amplitude imposed by wearing skates was found to
      significantly limit the knee joint amplitude while the hip angular motion was not
      affected. Neither the skates' mass nor the limited ankle angular motion modified
      the proximo-distal organization of joint co-ordination observed when jumping
      barefoot. However, with plantar flexion restriction, the delay between hip and
      knee extensions increased while it was reduced between knee and ankle extensions.
      Work output at the knee and ankle joints were significantly lowered when wearing
      skates. The decrease of work at the knee was shown to result from an early
      flexing moment causing a premature deceleration of the knee and from a reduction
      of knee amplitude. Taken together, these results show a minimization of the
      participation of the knee when plantar flexion is limited. It was proposed that
      constraining the distal joint causes a reorganization of interjoint co
      ordinations and a redistribution of the energy produced by knee extensors to the
      hip and ankle joints.

PMID- 16439240
TI  - Maximum isometric arm forces in the horizontal plane.
AB  - In this paper, we measured the maximum isometric force at the hand in eight
      directions in the horizontal plane and at five positions in the workplace. These
      endpoint forces were the result of shoulder horizontal adduction/abduction and
      elbow flexion/extension torques. We found that the normalized maximum forces of
      all the six subjects deviated less than 15%, despite intra-subject differences in
      muscle strength of more than a factor of two. The maximum forces were found to
      systematically depend on the force direction and on the hand position in the
      workspace. The largest forces were found in a direction approximately along the
      line connecting shoulder joint and hand, and the smallest forces perpendicular to
      that line, thereby forming an elliptically shaped pattern. The elongation of the
      pattern was the largest for those hand positions having the more extended elbow
      joint. By using a lumped six-muscle model, with two mono-articular muscle pairs
      and one bi-articular pair, we were able to predict the observed force patterns.
      Here, we assumed that one of the muscles generates its maximum force and the
      others adjust their output to point the endpoint force in the required direction.
      We used a principal component analysis of the surface EMGs of simultaneously
      measured representatives of four of the six muscles. With the same model, we were
      then able to determine the principal directions of all the six muscle groups.

PMID- 16439242
TI  - Three-dimensional in vivo motion of adult hind foot bones.
AB  - Knowledge of hind foot bone motion is important for understanding gait as well as
      various foot pathologies, but the three-dimensional (3D) motion of these bones
      remains incompletely understood. The purpose of this study was to quantify the
      motion of the talus, calcaneus, navicular, and cuboid in normal adult feet during
      open chain quasi-static uniplanar plantar flexion motion. Magnetic resonance
      images of the right feet of six normal young adult males were taken from which 3D
      virtual models were made of each hind foot bone. The 3D motion of these models
      was analyzed. Each hind foot bone rotated in the same plane about half as much as
      the foot (mean 0.54 degrees of bone rotation per degree of foot motion, range
      0.40-0.73 degrees per degree of foot motion as measured relative to the fixed
      tibia). Talar motion was primarily uniaxial, but the calcaneus, navicular, and
      cuboid bones exhibited biplanar (sometimes triplanar) translation in addition to
      biaxial rotation. Net translational motions of these bones averaged 0.39 mm of
      bone translation per degree of foot motion (range 0.06-0.62 mm per degree of foot
      motion). These data reflect the functional anatomy of the foot, extend the
      findings of prior studies, provide a standard for comparison to patients with
      congenital or acquired foot deformities, and establish an objective reference for
      quantitatively assessing the efficacy of various hind foot therapies.

PMID- 16439241
TI  - High resolution mechanical function in the intact porcine heart: mechanical
      effects of pacemaker location.
AB  - The necessity to quantify the mechanical function with high spatial resolution
      stemmed from the advancement of myocardial salvaging techniques. Since these
      therapies are localized interventions, a whole field technique with high spatial
      resolution was needed to differentiate the normal, diseased, and treated
      myocardium. We developed a phase correlation algorithm for measuring myocardial
      displacement at high spatial resolution and to determine the regional mechanical
      function in the intact heart. Porcine hearts were exposed and high contrast
      microparticles were placed on the myocardium. A pressure transducer, inserted
      into the left ventricle, synchronized the pressure (LVP) with image acquisition
      using a charge-coupled device camera. The deformation of the myocardium was
      measured with a resolution of 0.58+/-0.04 mm. Within the region of interest
      (ROI), regional stroke work (RSW), defined as the integral of LVP with respect to
      regional area, was determined on average at 21 locations with a resolution of
      27.1+/-2.7 mm2. To alter regional mechanical function, the heart was paced at
      three different locations around the ROI. Independent of the pacemaker location,
      RSW decreased in the ROI. In addition, a gradient of increasing RSW in the
      outward direction radiating from the pacemaker was observed in all pacing
      protocols. These data demonstrated the ability to determine regional whole field
      mechanical function with high spatial resolution, and the significant alterations
      induced by electrical pacing.

PMID- 16439244
TI  - Wall shear stress in normal left coronary artery tree.
AB  - Despite the fact that the role of wall shear stress (WSS) as a local mechanical
      factor in atherogenesis is well established, its distribution over the entire
      normal human left coronary artery (LCA) tree has not yet been studied. A three
      dimensional computer generated model of the epicardial LCA tree, based on
      averaged human data set extracted from angiographies, was adopted for finite
      element analysis of the Navier-Stokes flow equations treating blood as non
      Newtonian fluid. The LCA tree includes the left main coronary artery (LMCA), the
      left anterior descending (LAD), the left circumflex artery (LCxA) and their major
      branches. In proximal LCA tree regions where atherosclerosis frequently occurs,
      low WSS appears. Low WSS regions occur at bifurcations in regions opposite the
      flow dividers, which are anatomic sites predisposed for atherosclerotic
      development. On the LMCA bifurcation, at regions opposite to the flow divider,
      dominant low WSS values occur ranging from 0.75 to 2.25 N/m2. High WSS values are
      encountered at all flow dividers. This work determines, probably for the first
      time, the topography of the WSS in the entire normal human LCA epicardial tree.
      It is also the first work determining the spatial WSS differentiation between
      proximal and distal normal human LCA parts. The haemodynamic analysis of the
      entire epicardial LCA tree further verifies the implications of the WSS in
      atherosclerosis mechanisms.

PMID- 16439243
TI  - Stress-concentrating effect of resorption lacunae in trabecular bone.
AB  - Analyses of the distributions of stress and strain within individual bone
      trabeculae have not yet been reported. In this study, four trabeculae were imaged
      and finite elements models were generated in an attempt to quantify the
      variability of stress/strain in real trabeculae. In three of these trabeculae,
      cavities were identified with depths comparable to values reported for resorption
      lacunae ( approximately 50 microm)-although we cannot be certain, it is most
      probable that they are indeed resorption lacunae. A tensile load was applied to
      each trabeculum to simulate physiological loading and to ensure that bending was
      minimized. The force carried by each trabecula was calculated from this value
      using the average cross sectional area of each trabecula. The analyses predict
      that very high stresses (>100 MPa) existed within bone trabecular tissue. Stress
      and strain distributions were highly heterogeneous in all cases, more so in
      trabeculae with the presumptive resorption lacunae where at least 30% of the
      tissue had a strain greater than 4000 micoepsilon in all cases. Stresses were
      elevated at the pit of the lacunae, and peak stress concentrations were located
      in the longitudinal direction ahead of the lacunae. Given these high strains, we
      suggest that microdamage is inevitable around resorption lacunae in trabecular
      bone, and may cause the bone multicellular unit to proceed to resorb a packet of
      bone in the trabeculum rather than just resorb whatever localized area was
      initially targeted.

PMID- 16439245
TI  - Changes in axial stiffness of the trunk as a function of walking speed.
AB  - Research suggests that abnormal coordination patterns between the thorax and
      pelvis in the transverse plane observed in patients with Parkinson's disease and
      the elderly might be due to alteration in axial trunk stiffness. The purpose of
      this study was to develop a tool to estimate axial trunk stiffness during walking
      and to investigate its functional role. Fourteen healthy young subjects
      participated in this study. They were instructed to walk on the treadmill and
      kinematic data was collected by 3D motion analysis system. Axial trunk stiffness
      was estimated from the angular displacement between trunk segments and the amount
      of torque around vertical axis of rotation. The torque due to arm swing cancelled
      out the torque due to the axial trunk stiffness during walking and the thoracic
      rotation was of low amplitude independent of changes in walking speeds within the
      range used in this study (0.85-1.52 m/s). Estimated axial trunk stiffness
      increased with increasing walking speed. Functionally, the suppression of axial
      rotation of thorax may have a positive influence on head stability as well as
      allowing recoil between trunk segments. Furthermore, the increased stiffness at
      increased walking speed would facilitate the higher frequency rotation of the
      trunk in the transverse plane required at the higher walking speeds.

PMID- 16439246
TI  - The relationship between two different mechanical cost functions and muscle
      oxygen consumption.
AB  - Inverse-dynamic models often use cost functions to solve the load-sharing
      problem. Although it is often assumed that energy is minimised, most cost
      functions are based on mechanically related measures like muscle force or stress.
      The aim of this study was to analyse the relationships of two cost functions with
      experimentally determined data on muscle energy consumption. Four subjects
      performed isometric contractions generating combinations of elbow
      flexion/extension and pro/supination moments. Muscle oxygen consumption (VO2) of
      the m. biceps breve, m. biceps longum, m. brachioradialis and m. triceps laterale
      was measured with near infrared spectroscopy. Both cost functions were
      implemented into an existing inverse-dynamic shoulder and elbow model and the
      individual cost values per muscle were calculated, normalised and subsequently
      compared to experimental VO2 values. The minimum stress cost function led to a
      good correspondence between VO2 and cost for the m. triceps laterale but for the
      flexor muscles cost was significantly lower. A newly proposed energy-related cost
      function showed, however, a far better correspondence. The inclusion of a linear
      term and muscle mass in the new criterion led model results to correspond better
      to experimental results. The energy-related cost function appeared to be a better
      measure for muscle energy consumption than the stress cost function and led to
      more realistic predictions of muscle activation.

PMID- 16439247
TI  - Biomechanical comparison between fusion of two vertebrae and implantation of an
      artificial intervertebral disc.
AB  - Surgical treatments for lower back pain can be distributed into two main groups:
      fusion (arthrodesis) and disc replacement (arthroplasty). The objective of this
      study was to compare, under severe loading conditions, the biomechanics of the
      lumbar spine treated either by fusion or total disc replacement (TDR). A three
      dimensional model of a two-level ligamentous lumbar segment was created and
      simulated through static analyses with the finite-element method (FEM) software
      ABAQUS. The model was validated by comparing mobility, pressure on the facets,
      force in the ligaments, maximum stresses, disc bulge, and endplate deflection
      with measured data given in the literature. The FEM analysis predicted that the
      mobility of the model after arthrodesis on the upper level was reduced in all
      rotational degrees of freedom by an average of approximately 44%, relative to
      healthy normal discs. Conversely, the mobility of the model after TDR on the
      upper level was increased in all rotational degrees of freedom by an average of
      approximately 52%. The level implanted with the artificial disc showed excessive
      ligament tensions (greater than 500 N), high facet pressures (greater than 3
      MPa), and a high risk of instability. The mobility and the stresses in the level
      adjacent to the arthroplasty were also increased. In conclusion, the model for an
      implanted movable artificial disc illustrated complications common to spinal
      arthroplasty and showed greater risk of instability and further degeneration than
      predicted for the fused model. This modeling technique provides an accurate means
      for assessing potential biomechanical risks and can be used to improve the design
      of future artificial intervertebral discs.

PMID- 16439248
TI  - A method to synchronise video cameras using the audio band.
AB  - This paper proposes and evaluates a novel method for synchronisation of video
      cameras using the audio band. The method consists in generating and transmitting
      an audio signal through radio frequency for receivers connected to the microphone
      input of the cameras and inserting the signal in the audio band. In a software
      environment, the phase differences among the video signals are calculated and
      used to interpolate the synchronous 2D projections of the trajectories. The
      validation of the method was based on: (1) Analysis of the phase difference
      changes as a function of time of two video signals. (2) Comparison between the
      values measured with an oscilloscope and by the proposed method. (3) Estimation
      of the improvement in the accuracy in the measurements of the distance between
      two markers mounted on a rigid body during movement applying the method. The
      results showed that the phase difference changes in time slowly (0.150 ms/min)
      and linearly, even when the same model of cameras are used. The values measured
      by the proposed method and by oscilloscope showed equivalence (R2=0.998), the
      root mean square of the difference between the measurements was 0.10 ms and the
      maximum difference found was 0.31 ms. Applying the new method, the accuracy of
      the 3D reconstruction had a statistically significant improvement. The accuracy,
      simplicity and wide applicability of the proposed method constitute the main
      contributions of this work.

PMID- 16439249
TI  - Microfabricated refractive index gradient based detector for reversed-phase
      liquid chromatography with mobile phase gradient elution.
AB  - Typical refractive index (RI) detectors for liquid chromatography (LC) are not
      well suited to application with mobile phase gradient elution, due to the
      difficulty in correcting for the detected baseline shift during the gradient. We
      report a sensitive, highly reproducible, microfabricated refractive index
      gradient (micro-RIG) detector that performs well with mobile phase gradient
      elution LC. Since the micro-RIG signal remains on-scale throughout the mobile
      phase gradient, one can apply a baseline correction procedure. We demonstrate
      that by collecting two mobile phase gradient blanks and subtracting one of them
      from the other, a reproducible, flat baseline is achieved. Therefore, subtracting
      a blank from a separation provides a baseline corrected chromatogram with
      reasonably high signal-to-noise ratio for eluting analytes. The micro-RIG
      detector uses a collimated diode laser beam to optically probe a RIG formed
      perpendicular to the laminar flow direction within a microfabricated borosilicate
      glass chip. The chip-based design of the detector is suitable for either
      traditional bench-top or LC-on-a-chip technologies. We report reversed phase high
      performance liquid chromatography (RP-HPLC) separations of proteins and polymers,
      over mobile phase gradient conditions of 67% A:33% B to 3% A:97% B by volume,
      where A is 96% methanol:3.9% water:0.1% trifluoroacetic acid (TFA), and B is 3.9%
      methanol:96% water:0.1% TFA. The separations were performed on a Jupiter 5 mu C4
      300 A 150 mm x 1.0 mm Phenomenex column at a flow rate of 20 microl/min.
      Viscosity changes during the mobile phase gradient separation are found to shift
      the on-chip merge position of the detected concentration gradient (i.e., RIG), in
      a reproducible fashion. However, this viscosity effect makes detection
      sensitivity vary throughout the mobile phase gradient, due to moving the
      optimized position of the probe beam in relation to the analyte concentration
      gradient being probed. None-the-less, consistent limits of detection (LODs) were
      achieved. The 3-sigma deflection angle LOD was 16 microrad for micro-RIG
      detection, corresponding to an injected concentration LOD of 7 ppm (mass/mass)
      for cytochrome c.

PMID- 16439250
TI  - Fast enantiomeric analysis of a complex essential oil with an innovative
      multidimensional gas chromatographic system.
AB  - The present research is focussed on the evaluation of a recently developed high
      performance multidimensional gas chromatographic (MDGC) system employed in the
      fast analysis of a series of chiral compounds contained in rosemary essential
      oil. The heart of the MDGC system consists in a simple transfer device for the
      rapid sequential re-injection of analyte "heart-cuts" from the first to the
      second dimension. The transfer system has no temperature restrictions, presents
      very low dead volumes and achieves multidimensional analysis through a pressure
      balance mechanism. The MDGC set-up is characterized by two GC ovens (enabling
      independent temperature programming) and the possibility of mass spectrometric
      (MS) and/or flame ionization detection (FID). Multiple-cut conventional and fast
      MDGC-FID methods were developed and the results obtained compared, in order to
      evaluate the effectiveness of the system. In this respect, the rapid method
      provided the same analytical result in a greatly reduced time (approximately five
      times less). Furthermore, quali/quantitative data reproducibilty was very good.
      Fast MDGC was achieved by using micro-bore (0.1mm I.D.) columns in both
      dimensions.

PMID- 16439252
TI  - Development of a removable multi-column-switching system for gas chromatography.
AB  - A removable column-switching device for a commercially available gas
      chromatograph has been developed. To this end, the challenges of the equipment's
      high temperature stability, of the flow of gas through stand-by columns, of
      catalytically effective stainless steel surfaces, of the cooling trap effects
      within valves and the limited oven space are dealt with. The developed column
      switching system was investigated in terms of dead volume (tailing factor),
      adsorption (Grob test) and degradation (Endrin test). This GC column-switching
      system shows comparable results with analyses that do not employ column
      switching. For example, it was possible to avoid effects, such as adsorption and
      decomposition. This system can automatically test the suitability of as many as
      eight separating columns to analyze unknown samples. The GC column-switching
      system thus serves to increase efficiency in the selection or screening of
      stationary phases with GC method developments.

PMID- 16439251
TI  - Characterization of bovine serum albumin-tryptophan interaction by capillary
      isoelectric focusing with whole column imaging detection.
AB  - Capillary isoelectric focusing (cIEF) with whole column imaging detection (WCID)
      was explored for the characterization of bovine serum albumin (BSA)-tryptophan
      interaction, to further understand protein-drug interactions. The BSA-tryptophan
      interaction was dynamically monitored by cIEF-WCID, to provide the cIEF profiles
      of the BSA-tryptophan interaction system at different focusing times. Our study
      demonstrated that the cIEF behavior of BSA can serve as a probe into the study of
      BSA-tryptophan interaction, through monitoring the change in its cIEF profile
      when the interaction occurred. The study illustrated that the BSA peak split due
      to the BSA-tryptophan interaction, and the peak of BSA-tryptophan complex was
      clearly identified in the cIEF electropherograms. By comparing the cIEF profiles
      of BSA/L-tryptophan and BSA/D-tryptophan, respectively, our study demonstrated
      that BSA interacted with the enantiomers of tryptophan with a chiral recognition.
      L-Tryptophan demonstrated a very strong interaction with BSA, while D-tryptophan
      exhibited a much weaker interaction with BSA. The effects of the BSA
      concentration, the tryptophan concentration, the focusing time and the incubation
      time on the BSA-tryptophan interaction were investigated. This study offers a
      novel approach for the study of protein-drug interactions.

PMID- 16439253
TI  - Analysis of tert-butyldimethylsilyl derivatives in heavy gas oil from Brazilian
      naphthenic acids by gas chromatography coupled to mass spectrometry with electron
      impact ionization.
AB  - Naphthenic acids, C(n)H(2n+Z)O(2), are a complex mixture of alkyl-substituted
      acyclic and cycle-aliphatic carboxylic acids. The content of naphthenic acids and
      their derivatives in crude oils is very small, which hinders their extraction
      from matrixes of wide and varied composition. In this work, liquid-liquid
      extraction, followed by solid phase extraction with an ion exchange resin
      (Amberlyst A-27) and ultrasound desorption were used to isolate the acid fraction
      from heavy gas oil of Marlim petroleum (Campos, Rio de Janeiro, Brazil). The
      analysis was accomplished through gas chromatography coupled to mass spectrometry
      with electron impact ionization, after derivatization with N-methyl-N-(tert
      butyldimethylsilyl)trifluoracetamide (MTBDMSTFA). The results indicate the
      presence of carboxylic acids belonging to families of alicyclic and naphthenic
      compounds which contain up to four rings in the molecule.

PMID- 16439254
TI  - Analysis of free amino acids in fermented shrimp waste by high-performance liquid
      chromatography.
AB  - This work presents an HPLC method for the quantification of free amino acids in
      lyophilized protein fraction from shrimp waste hydrolysate which is obtained by
      acid lactic fermentation and analyzed using pre-column derivatization with 9
      fluorenylmethyl-chloroformate. The amino acids were separated in a Hypersil ODS 5
      microm column (250 mm x 4.6 mm) at 38 degrees C. The mobile phase was a mixture
      of phase A: 30 mM ammonium phosphate (pH 6.5) in 15:85 (v/v) methanol/water;
      phase B: 15:85 (v/v) methanol/water; and phase C: 90:10 (v/v) acetonitrile/water,
      with flow rate 1.2 ml/min. Fluorescence detection was used at an excitation
      wavelength of 270 nm and an emission wavelength of 316 nm. Method precisions for
      the different amino acids were between 4.4 and 7.1% (relative standard deviation,
      RSD); detection limits were between 23 and 72 ng/ml; and the recoveries were
      between 89.0 and 95.0%. The amino acid present at the highest concentration was
      tyrosine.

PMID- 16439255
TI  - High-performance liquid chromatography method to measure alpha- and gamma
      tocopherol in leaves, flowers and fresh beans from Moringa oleifera.
AB  - A high-performance liquid chromatography method for the microscale determination
      of alpha- and gamma-tocopherol in leaves, flowers and fresh beans from Moringa
      oleifera is reported. The method includes microscale saponification and
      extraction with n-hexane. Optimized conditions for reversed-phase HPLC with UV
      detection were as follows: column, 25 cm x 0.46 cm, Exil ODS 5-microm; column
      temperature, 25 degrees C; mobile phase, a 20:80 (v/v) mixture of
      methanol:acetonitrile; flow rate, 1.0 ml/min. With these conditions, method
      precision (relative standard deviation) was 5.6% for alpha-tocopherol and 4.9%
      for gamma-tocopherol. We used this method to measure alpha- and gamma-tocopherol
      in samples from M. oleifera as part of nutritional studies in edible plants
      cultivated in the Northwest Mexico.

PMID- 16439256
TI  - Comparison of soxhlet, ultrasound-assisted and pressurized liquid extraction of
      terpenes, fatty acids and Vitamin E from Piper gaudichaudianum Kunth.
AB  - This paper describes a comparative study of extraction methods of terpenes
      (terpenic alcohols and phytosterols), fatty acids and Vitamin E from leaves of
      Piper gaudichaudianum Kunth. The analysis of extracts was done by gas
      chromatography with mass spectrometric detection. The identification and
      quantification was made by co-injections of the extract with certified standards.
      The use of pressurized liquid extraction (PLE; Dionex trade name: ASE, for
      accelerated solvent extraction) decrease significantly the total time of
      extraction, the amount of solvent and the manipulation of sample and solvents in
      comparison with soxhlet (SE) and ultrasound-assisted (USE). In addition, PLE was
      more effective for the extractions of terpenes (terpenic alcohols and
      phytosterols), fatty acids and Vitamin E.

PMID- 16439257
TI  - Analysis of perfluorooctanesulfonate and related fluorochemicals in water and
      biological tissue samples by liquid chromatography-ion trap mass spectrometry.
AB  - A method for the determination of perfluorinated compounds (PFCs) in various
      water and biological tissue samples was developed and validated. The contents of
      selected PFCs (i.e., perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA)
      and perfluorodecanoate (PFDA)) in water samples were extracted by the C(18) solid
      phase extraction (SPE). The biological tissue samples (frozen-dried fish and
      oysters) were simply extracted by liquid-solid extraction with MTBE and adding
      tetrabutylammonium hydrogensulfate (TBA) as an ion-pairing reagent. The analytes
      were then identified and quantitated by liquid chromatography-ion trap negative
      electrospray mass spectrometry (LC-ESI ion-trap-MS). Limits of quantitation (LOQ)
      were established between 0.5 and 6 ng/l in 250 ml of water sample, while 5-50
      ng/g (dry weight) for biological tissue sample. Intrabatch and interbatch
      precision with their accuracy at two concentration levels were also investigated.
      Precision for these three PFCs, as indicated by RSD, proved to be less than 11
      and 17%, respectively. The total contents of PFOA, PFOS and PFDA were detected in
      concentrations of up to 400 ng/l in various water samples, while up to 1,100 ng/g
      in fish and oyster samples. PFOA and PFDA was the major PFCs detected in water
      samples and biological tissue samples, respectively.

PMID- 16439258
TI  - Determination of aristolochic acid in Chinese herbal medicine by capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - We have demonstrated the analysis of aristolochic acids (AAs) that are naturally
      occurring nephrotoxin and carcinogen by capillary electrophoresis in conjunction
      with laser-induced fluorescence detection (CE-LIF). Owing to lack of intrinsic
      fluorescence characteristics of oxidized AAs (OAAs), reduction of the analytes by
      iron powder in 10.0 mM HCl is required prior to CE analysis. The reduced AAs
      (RAAs) exhibit fluorescence at 477 nm when excited at 405 nm using a solid-state
      blue laser. By using 50.0 mM sodium tetraborate (pH 9.0) containing 10.0 mM SDS,
      the determination of AA-I and AA-II by CE-LIF has been achieved within 12 min.
      The CE-LIF provides the LODs of 8.2 and 5.4 nM for AA-I and AA-II, respectively.
      The simple CE-LIF method has been validated by the analysis of 61 Chinese herbal
      samples. Prior to CE analysis, OAAs were extracted by using 5.0 mL MeOH, and then
      the extracts were subjected to centrifugation at 3,000 rpm for 5 min. After
      reduction, extraction, and centrifugation, the supernatants were collected and
      subjected to CE analysis. Of the 61 samples, 14 samples contain AA-I and AA-II,
      as well as 10 samples contain either AAI or AAII. The relative standard deviation
      (RSD) values of the migration times for AA-I and AA-II are less than 2.5% and
      2.1% for three consecutive measurements of each sample. The RSD values for the
      peak heights corresponding to AA-I and AA-II in most samples are about 8.0% and
      10.0%, respectively. The result shows that the present CE-LIF approach is
      sensitive, simple, efficient, and accurate for the determination of AAs in real
      samples.

PMID- 16439259
TI  - High-performance liquid chromatography method for the simultaneous quantification
      of retinol, alpha-tocopherol, and cholesterol in shrimp waste hydrolysate.
AB  - This study presents an HPLC method for the simultaneous quantification of
      retinol, alpha-tocopherol, and cholesterol in shrimp waste hydrolysate lipid
      fraction. The method includes microscale saponification and extraction with n
      hexane. Liposoluble vitamins and cholesterol were quantified by HPLC with UV
      detection (HPLC-UV), on a 25 cm x 0.46 cm SS Exil ODS 5 microm column, mobile
      phase 68:28:4 (v/v/v) methanol:acetonitrile:water; flow rate 1.4 ml/min; column
      temperature 36 degrees C. The detection was operated using two channels of a
      diode-array spectrophotometer, 325 nm for retinol and 208 nm for alpha-tocopherol
      and cholesterol. With these conditions, the overall recovery was 95.7, 100.8, and
      98.0% for retinol, alpha-tocopherol, and cholesterol, respectively. The method
      precision (relative standard deviation) was 1.83% for retinol, 2.32% for alpha
      tocopherol, and 1.98% for cholesterol. This method was used to quantify the cited
      analytes in the hydrolysate obtained during lactic acid fermentation of shrimp
      waste. This hydrolysate may be a valuable supplement of nutrients in fish
      production.

PMID- 16439260
TI  - Dual derivatization-stir bar sorptive extraction--thermal desorption--gas
      chromatography-mass spectrometry for determination of 17beta-estradiol in water
      sample.
AB  - A novel method for the trace analysis of 17beta-estradiol (E2) in river water
      sample was developed, which involved stir bar sorptive extraction (SBSE) with in
      situ acylation (first derivatization) and thermal desorption (TD) with quartz
      wool assisted (QWA) in tube silylation (second derivatization), followed by gas
      chromatography-mass spectrometry (GC-MS), and is called the "dual derivatization
      method." The optimum conditions for SBSE with in situ acylation, such as the
      volume of acetic acid anhydride and the extraction time, were investigated. In
      addition, the optimum conditions for TD with QWA in tube silylation, such as the
      volume of N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and the TD
      temperature and hold time, were investigated as well. The detection limit (S/N =
      3) and the quantitation limit (S/N>10) of E2 in the river water sample were 0.5
      and 2 pg ml(-1) (ppt), respectively, by the dual derivatization method. In
      addition, the detection limit was 0.1 pg ml(-1) by using dual derivatization
      method with multi-shot mode. The calibration curve for E2 was linear in the range
      of 0.002-10 ng ml(-1) with correlation coefficients >0.999. The average
      recoveries of E2 (n = 6) at the concentrations of 0.05 and 1.0 ng ml(-1) from the
      river water sample were 93.1 (RSD: 1.4%) and 98.4% (RSD: 0.8%), respectively,
      with correction using the added surrogate standard, 17beta-estradiol-(13)C(4).
      This simple, accurate, sensitive and selective analytical method may be
      applicable to the determination of trace amounts of E2 in water samples.

PMID- 16439261
TI  - Optimization of pressurized liquid extraction of Piper gaudichaudianum Kunth
      leaves.
AB  - Piperaceae family is original from tropical regions and it shows more than 700
      species around the world. Piper gaudichaudianum Kunth is the specie more abundant
      in Brazil, occurring from Northeast to South Brazil. In this paper, it was
      investigated the influence of some experimental parameters on the pressurized
      liquid extraction (PLE) of P. gaudichaudianum Kunth leaves, using petroleum ether
      as extractor solvent. The optimization of the main variables involved in the PLE
      process (extraction temperature and time) has been done by response surface
      methodology (RSM) using, as responses, the extraction yield and the
      chromatographic profile (GC/MS) of the extracts. The optimized procedure employed
      3 g of ground leaves, 10 min of extraction and one cycle of extraction at 85
      degrees C. The major compounds present in the petroleum ether extracts were:
      palmitic acid, stearic acid and nerolidol. The results presented in this work
      show the possibility of using a fast and easy process to recover compounds from
      P. gaudichaudianum Kunth.

PMID- 16439262
TI  - Flow-through system for the generation of standard aqueous solution of polycyclic
      aromatic hydrocarbons.
AB  - Standard aqueous solution of organic pollutants is used for the development of
      analysis methods and novel water sampling devices. The use of solid-phase
      microextraction (SPME) and other novel technologies for research in water
      sampling and analysis requires systems for the reliable generation of standard
      aqueous solution. In this communication, a new flow-through system based on
      permeation is introduced for the generation of standard aqueous solution of
      polycyclic aromatic hydrocarbons (PAHs). The main difference between the new
      developed system and typical system is that the syringe pump was changed with a
      permeation generator. The generator-based permeation offers many advantages,
      including convenient, inexpensive, solvent-free, long lifetime and production of
      high concentrations of the target analytes. The observed change in the
      concentration of the six PAH compounds was less than 20% over 3 months.

PMID- 16439263
TI  - The perseverative cognition hypothesis: a review of worry, prolonged stress
      related physiological activation, and health.
AB  - Perseverative cognition, as manifested in worry and rumination, is a common
      response to stress, but biopsychological models of stress and health have largely
      ignored it. These models have generally focused on physiological activation that
      occurs during stress and have insufficiently addressed effects that occur in
      anticipation of, or following, stressful events. We argue that perseverative
      cognition moderates the health consequences of stressors because it can prolong
      stress-related affective and physiological activation, both in advance of and
      following stressors. We review evidence that worry, rumination, and anticipatory
      stress are associated with enhanced cardiovascular, endocrinological,
      immunological, and neurovisceral activity. The findings yield preliminary support
      for our hypothesis, suggesting that perseverative cognition might act directly on
      somatic disease via enhance activation via the cardiovascular, immune, endocrine,
      and neurovisceral systems.

PMID- 16439264
TI  - An international study comparing the effect of medically explained and
      unexplained somatic symptoms on psychosocial outcome.
AB  - OBJECTIVE: Cross-sectional studies show an association between somatic symptoms
      and psychiatric morbidity in primary care. However, medically explained and
      unexplained symptoms have been considered separately as distinct and unrelated.
      In addition, data on outcome in primary care are equivocal. We compare the effect
      of both constructs (medically explained and unexplained symptoms) on psychiatric
      morbidity and disability (social and physical) at 1 year follow-up. METHOD: Of
      5447 patients presenting for primary care in 14 countries, 3201 participants were
      followed up (72% compliance). We measured physical, psychiatric, and social
      status using standardised instruments. RESULTS: Patients with five or more
      somatic symptoms had increased psychosocial morbidity and physical disability at
      follow-up, even after controlling for confounders such as sociodemographics and
      recognition or treatment by general practitioners. There was little difference in
      outcome between medically explained and unexplained symptoms. CONCLUSIONS:
      Somatic symptoms-irrespective of aetiology-are associated with adverse
      psychosocial and functional outcome in diverse cultures.

PMID- 16439265
TI  - Medically unexplained cutaneous sensory symptoms may represent somatoform
      dissociation: an empirical study.
AB  - OBJECTIVE: We examined the relation between medically unexplained cutaneous
      symptoms and dissociation [measured by the Dissociative Experiences Scale, or
      DES; Bernstein EM, Putnam FW. Development, reliability, and validity of a
      dissociation scale. J Nerv Ment Dis 1986;174:727-35] among participants with no
      history of primary dermatologic disorders. METHODS: Three hundred sixty
      consenting participants (44 psychiatric outpatients and 316 nonclinical
      participants from the community at large) rated the severity of nine medically
      unexplained cutaneous symptoms (sum of all ratings comprised the Cutaneous9
      variable) and completed the DES. RESULTS: The Cutaneous9 variable correlated
      significantly (Pearson r=.56, P<.001) with DES scores. Stepwise multiple
      regression analysis using the nine cutaneous symptoms as independent variables
      revealed that Pain, Itching, and Numbness were the best predictors of the DES
      scores (adjusted R2=.34, P<.001). CONCLUSION: Our findings have empirically shown
      that itching, like pain and numbness, may be a symptom of somatoform
      dissociation. Second, even milder degrees of dissociation in the nonclinical
      range may play a role in the genesis of unexplained cutaneous sensory symptoms.

PMID- 16439266
TI  - Dimensionality of the Whiteley Index: assessment of hypochondriasis in an
      Australian sample of primary care patients.
AB  - OBJECTIVE: The Whiteley Index (WI) is a widely used instrument for measuring
      hypochondriacal worries and beliefs. Several studies explored the structural
      validity of the WI obtaining contrary results concerning the number of factors as
      well as the item composition. The main aim of this study is to compare factor
      solutions from previous studies to draw conclusions about the most valid scale
      model of the WI for administration in primary care. METHODS: Weighted least
      squares (WLS) confirmatory factor analyses of the WI were conducted. The sample
      in study consisted of 1800 patients from primary care practices. Seven different
      models were compared, including single- and three-factor conceptualisations.
      RESULTS: A seven-item, single-factor model best described the data, while three
      factor models were clearly inadequate. CONCLUSIONS: Results support a one
      dimensional conceptualisation of the WI and suggest a certain subscale of the WI,
      the WI-7, to constitute the most psychometrically sound scale for use as a
      screening instrument for hypochondriasis in primary care. In addition to
      psychometric considerations, the brevity and simplicity of the WI-7 also make it
      attractive as a screening tool in the context of primary care. A cutoff score of
      2/3, calculated on the basis of general practitioners' diagnoses, yielded the
      best balance of sensitivity and specificity in the present study.

PMID- 16439267
TI  - Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in
      chronic fatigue syndrome.
AB  - OBJECTIVE: The aim of this study was to obtain comprehensive information on basal
      hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome
      (CFS) patients who were not affected by medication or comorbid psychiatric
      disorder likely to influence the HPA axis. METHOD: Steroid analysis of urine
      collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls.
      RESULTS: Urinary free cortisol and cortisone concentrations showed a significant
      normal diurnal rhythm, but levels were lower across the cycle in CFS. In
      contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm,
      levels were not significantly different between the CFS and controls at any time.
      Derived metabolite ratios were similar in both groups. CONCLUSION: This study
      provides further evidence for reduced basal HPA axis function in patients with
      CFS, based on lower free cortisol and cortisone levels, but this is not
      corroborated by cortisol metabolite data. The difference between these measures
      cannot be explained by an altered timing of the diurnal rhythm.

PMID- 16439268
TI  - Health anxiety levels in chronic pain clinic attenders.
AB  - OBJECTIVE: An application of the cognitive-behavioural model of health anxiety
      (hypochondriasis) to chronic pain depends on the extent to which high levels of
      health anxiety occur in chronic pain, which has yet to be established. METHODS:
      The occurrence of health anxiety in consecutively recruited chronic pain patients
      (n=161) and nonclinical controls with (n=34) and without pain (n=70) was
      investigated using a questionnaire measure of health anxiety. RESULTS:
      Conservative figures estimated a frequency of 36.7% for hypochondriasis and 51.1%
      of severe and disabling health anxiety in the chronic pain sample. CONCLUSION:
      The current finding that high levels of health anxiety are indeed very common in
      chronic pain indicates the potential value of an application of the cognitive
      behavioural health anxiety model to at least the subgroup of highly health
      anxious chronic pain patients.

PMID- 16439269
TI  - Lasting impressions: influence of the initial hospital consultation for chronic
      pelvic pain on dimensions of patient satisfaction at follow-up.
AB  - OBJECTIVE: Chronic pelvic pain (CPP) is a common condition in women, and care
      experiences are distressing and unsatisfactory for many. Research suggests that
      elements of the initial hospital consultation influence clinical outcome. This
      study aimed to identify the dimensions through which initial consultations were
      subsequently recalled at follow-up. METHOD: A questionnaire study of 100 women, 6
      months following a hospital gynaecology consultation for CPP, was conducted.
      Measures of pain and ratings of the medical consultation were completed at
      initial consultation and at follow-up. RESULTS: Follow-up questionnaire items
      loaded to constructs of "affect", "expectation", and "cognition", forming three
      subscales. Patients' initial ratings of the consultation and scores on all three
      subscales measured at follow-up were correlated, remaining significant for both
      affect and expectation after controlling for current pain status. CONCLUSION:
      Doctor's affect and the appropriateness of information to meet expectations are
      important influences on experiences of care and contribute to the long-term
      therapeutic element of the consultation.

PMID- 16439270
TI  - Mental vulnerability--a risk factor for ischemic heart disease.
AB  - OBJECTIVE: The purpose of this study is to examine whether mental vulnerability
      is a risk factor for the development of ischemic heart disease (IHD) after
      adjustment for well-established risk factors. METHODS: In three prospective
      cohort studies in Copenhagen County, Denmark, we recorded the level of mental
      vulnerability and possible risk factors to IHD at baseline. For follow-up, the
      sample was linked to relevant registries to identify all cases of fatal and
      nonfatal IHD. The relationship between mental vulnerability and IHD was examined
      using both Kaplan-Meir and Cox proportional hazard models adjusting for possible
      confounding factors. RESULTS: Mental vulnerability was significantly associated
      with the risk for IHD (medium mental vulnerability: hazard ratio 1.41, 95%
      confidence interval 1.04-1.91; and high mental vulnerability: hazard ratio 2.05;
      95% confidence interval 1.46-2.88), after adjusting for confounders. CONCLUSION:
      Our results imply that mental vulnerability is an independent risk factor for
      IHD.

PMID- 16439271
TI  - Validation of the Cardiac Depression Scale in a cardiac rehabilitation
      population.
AB  - OBJECTIVE: The current study was undertaken to provide further evidence
      supporting the reliability and validity of the Cardiac Depression Scale (CDS) in
      a population of cardiovascular patients. METHODS: The CDS was administered to 627
      consecutive ambulatory adult cardiac patients attending an outpatient Cardiac
      Rehabilitation program, and a subgroup also completed the Geriatric Depression
      Scale--Short Form (GDS-SF). RESULTS: Factor analysis revealed six subscales
      accounting for 62% of scale variance. The CDS demonstrated high internal
      consistency (Cronbach's alpha=.92) and correlation coefficient with the GDS-SF of
      .77. Receiver operating characteristic curves suggested a CDS cutoff score of 100
      to detect more severe depression, and 90 to detect mild to moderate depression.
      CONCLUSION: These findings encourage the continued use and evaluation of the CDS
      for measuring symptoms of depressive affect in cardiac patients.

PMID- 16439272
TI  - Social support and change in health-related quality of life 6 months after
      coronary artery bypass grafting.
AB  - OBJECTIVE: We determined whether perceived social support predicted change in
      health-related quality of life, operationalized as change in mental health and
      physical functioning, 6 months after coronary artery bypass grafting (CABG).
      METHODS: A prospective cohort of 1164 patients undergoing first CABG was
      interviewed prior to hospital discharge and 6 months later. Perceived
      instrumental and emotional support were assessed predischarge. Change in mental
      health and physical functioning was calculated as the difference between 6-month
      and predischarge SF-36 subscale scores. Stepwise linear regression analyses
      controlling for prior health-related quality of life, demographics, and clinical
      presentation were conducted. RESULTS: A total of 1072 (1072/1164=92%)
      participants completed the 6-month interview; mean age 65.7 (+/-11.1) years.
      Frequent instrumental support predicted positive change in mental health
      (beta=3.27, P=.02); change scores were higher when participants had low pre-CABG
      mental health. Neither social support variable predicted change in physical
      functioning. CONCLUSIONS: Assessing perceived instrumental support may help
      clinicians predict post-CABG mental health. More research regarding this
      relationship is needed before recommending intervention efforts.

PMID- 16439273
TI  - Are men more depressed than women in Norway? Validity of the Hospital Anxiety and
      Depression Scale.
AB  - OBJECTIVE AND METHODS: The aim was to evaluate the depression subscale of the
      Hospital Anxiety and Depression Scale (HADS-D) by comparing the gender-specific
      scores with another self-rated measure of mental health (MH), the SF-12 Health
      Survey, in a large general population (N=16,116). RESULTS: Using a score of 8 as
      a cut-off point for depression, the odds ratio for depression among men versus
      women was 1.29 [P<.0001; 95% confidence interval (CI): 1.16-1.43]. This
      contrasted with the results from the SF-12, in which the women had markedly and
      significantly poorer scores than men did. The women also reported a higher use of
      medicine for depression. Two of the seven HADS-D questions, related to interest
      in personal appearance and the ability to enjoy television, radio, and books,
      explained 70% of the higher depression scores among men. CONCLUSION: The results
      suggest that the validity related to gender differences in HADS-D is highly
      questionable.

PMID- 16439274
TI  - Chemosensory function and psychological profile in patients with multiple
      chemical sensitivity: comparison with odor-sensitive and asymptomatic controls.
AB  - OBJECTIVE: We addressed the question if patients with multiple chemical
      sensitivity (MCS) differ from participants with self-reported odor sensitivity
      without MCS and asymptomatic controls in terms of chemosensory, cognitive, and
      clinical psychological endpoints. METHODS: In a clinical study 23 MCS patients,
      21 participants with self-reported odor sensitivity, and 23 controls were
      investigated using electrophysiological and psychophysical olfactometric tests
      [chemosensory-event-related potentials (CSERP), olfactory thresholds, odor
      identification, trigeminal sensitivity]. The participants filled in a mood list,
      a list of complaints (BL), a Symptom Check List, a State-Trait Anxiety Inventory
      (STAI), and an MCS questionnaire. RESULTS: The olfactometric investigations
      revealed no significant differences between the groups. The MCS group reached
      significantly higher scores on negative mood states following odorant exposure,
      on health complaints, global indices, and the somatization subscale of the
      Symptom Check List, trait and state anxiety and symptoms, and triggering matters
      of the MCS questionnaire. CONCLUSIONS: Our findings reveal that neither olfactory
      functions, nor chemosensory or cognitive olfactory information processing are
      impaired in MCS patients. They rather support findings of altered psychological
      profile and moderate psychopathology.

PMID- 16439275
TI  - General hospital psychiatry in Italy: an update.

PMID- 16439280
TI  - ED/cardiology collaborative approach applauded.

PMID- 16439281
TI  - Intimate partner violence against women: findings from one state's ED
      surveillance system.
AB  - INTRODUCTION: Victims of intimate partner violence against women (IPVAW) often
      come into contact with various health care professionals, including emergency
      nurses. Michigan has implemented an ED surveillance system to monitor IPVAW in
      the state. METHODS: Twenty-three emergency departments participate in the
      Michigan Intimate Partner Violence Surveillance System. Female assault and
      maltreatment victims are identified using International Classification of
      Diseases Clinical Modification (ICD-9-CM) diagnostic and E codes (External Cause
      of Injury/Adverse Effects codes). For a 2-year period (1999-2000), patients'
      charts were reviewed, usually by an emergency nurse, to identify IPVAW victims.
      RESULTS: A total of 3111 female assault and maltreatment victims were identified.
      Of the 2926 incidents for which physical and/or sexual violence was confirmed by
      chart review, 1136 (38.8% [95% confidence interval: 37.1% to 40.6%]) involved
      IPVAW. DISCUSSION: A hospital ED surveillance system revealed that more than a
      third of female assault and maltreatment incidents were attributable to intimate
      partner violence, with a considerable proportion being young women abused by an
      ex-boyfriend. Surveillance also identified a need for improved documentation of
      female assault and maltreatment in ED records. We realized the benefits of using
      a public health surveillance process to monitor IPVAW incidence, identify high
      risk groups, and reduce research costs.

PMID- 16439282
TI  - Research education needs of pediatric emergency nurses.
AB  - INTRODUCTION: Evidence-based practice in the emergency care of children is
      critical. The Pediatric Emergency Care Applied Research Network (PECARN) was
      developed to increase pediatric research; however, participation by emergency
      nurses has been limited. To identify research needs in order to increase research
      involvement, the Emergency Nurses Association (ENA) conducted a research needs
      assessment with nurses in PECARN emergency departments. METHODS: A self
      administered needs assessment questionnaire was completed by 216 ED managers and
      nurses in 26 PECARN emergency departments between August and November of 2004.
      The questionnaires included items about research education, knowledge, and
      experience, as well as barriers to and resources for conducting research.
      Descriptive statistics were used to analyze the data. RESULTS: The primary
      barriers to nurses' research involvement included limited research knowledge and
      experience, limited awareness and availability of research resources, lack of
      dedicated time, and limited recognition for research contributions. However, the
      nurses reported moderate to extensive interest in research continuing education
      and desired moderate to extensive involvement in pediatric research. DISCUSSION:
      The nurses worked in research institutions with increased access to subjects and
      collaborative opportunities, indicating strong potential for nurses' research
      involvement. However, few institutions had practice models that included research
      recognition and dedicated research time. Furthermore, limited knowledge,
      experience, and awareness of research resources added to the barriers that
      reduced research involvement. To begin addressing the barriers, ENA developed a
      research curriculum based on the continuing education needs and interests
      identified by the nurses.

PMID- 16439283
TI  - Report of the National Consensus Conference on Family Presence During Pediatric
      Cardiopulmonary Resuscitation and Procedures.
AB  - Representatives from 18 national organizations were convened for a conference to
      develop recommendations regarding family presence (FP) during pediatric
      procedures and cardiopulmonary resuscitation. Before the conference, invitees
      were given a questionnaire and provided with current literature regarding FP. A
      modified Delphi process was used to develop consensus, including use of multiple
      questionnaires and breakouts for discussion of specific issues. Participants were
      encouraged to develop consensus recommendations based on the literature and
      discussions. Changes in attitude were tracked with repeat questionnaires. Results
      of the conference were circulated to participants for review and revision.
      Consensus recommendations include (1) consider FP as an option for families
      during pediatric procedures and cardiopulmonary resuscitation, (2) offer FP as an
      option after assessing factors that could adversely affect the interaction, (3)
      if family is not offered the option for FP, document the reasons why, (4) always
      consider the safety of the health care team, (5) develop in-hospital transport
      and transfer policies and procedures for FP, such as family member definition,
      preparation of the family, handling disagreements, and providing support for the
      staff, (6) obtain legal review of policies, (7) include education in FP in all
      core curricula and orientation for health care providers, (8) promote research
      into best methods for education; effects of FP on patients, family, and staff;
      best practices for FP; and legal issues regarding FP, among others. These
      recommendations were approved in concept by the American Academy of Pediatrics
      and the Ambulatory Pediatrics Association.

PMID- 16439284
TI  - The life and death of Edith Cavell, English emergency nurse known as "the other
      Nightingale".

PMID- 16439285
TI  - A 1908 ED Admission Log from Los Angeles' Central Receiving Hospital: excerpts
      and reflections.

PMID- 16439286
TI  - Emergency Nurses Association position statement: crowding in the emergency
      department.

PMID- 16439287
TI  - A 37-year-old with vomiting and severe, left-sided abdominal pain 3 years after
      gastric bypass surgery.

PMID- 16439288
TI  - A 21-year-old woman from Africa with fever, anemia, and jaundice 7 days after
      arriving in the US.

PMID- 16439289
TI  - More on the emergency response to the Gulf Coast devastation by hurricanes
      Katrina and Rita: experiences and impressions.

PMID- 16439290
TI  - American Heart Association releases new guidelines.

PMID- 16439291
TI  - Ambulance exhaust: exhausting our lungs.

PMID- 16439292
TI  - Consider eliminating auto-flush toilets in hospital areas with obstetrical
      gynecology patients: a case report.

PMID- 16439294
TI  - Automated medication dispensing systems: not error free.

PMID- 16439293
TI  - Giving liquid medications to pediatric patients.

PMID- 16439295
TI  - Providing consistent medical coverage at community events: North Carolina Rex
      Hospital's Emergency Response Team.

PMID- 16439296
TI  - Right ankle dislocation and fracture.

PMID- 16439297
TI  - Multicultural baby shower: Kansas City Truman Medical Center Trauma Services'
      unique way of teaching child passenger safety.

PMID- 16439300
TI  - An algorithm for triaging commonly missed causes of acute abdominal pain.

PMID- 16439301
TI  - Cardiac anomalies in the neonate: high index of suspicion important.

PMID- 16439302
TI  - Acetadote (intravenous acetylcysteine): adverse effects more significant than
      with oral acetylcysteine.

PMID- 16439303
TI  - End-of-life and palliative care in the emergency department: a call for research,
      education, policy and improved practice in this frontier area.

PMID- 16439304
TI  - A case report of traumatic eye compartment syndrome.

PMID- 16439305
TI  - Writing effective test questions to measure triage competency: tips for making a
      good triage test.

PMID- 16439306
TI  - Tumours can adapt to anti-angiogenic therapy depending on the stromal context:
      lessons from endothelial cell biology.
AB  - It has long been recognized that interference with the blood supply of a tumour
      is an effective way to halt tumour progression, and even induce tumour
      regression. This can be accomplished by anti-angiogenic treatment which prevents
      the formation of a tumour neovasculature, or anti-vascular treatment, which aims
      at destruction of existent tumour vessels. The latter has received relatively
      little attention because there is a lack of specific tumour-endothelial markers.
      Instead, the current detailed knowledge on the factors and mechanisms, involved
      in angiogenesis, has enabled the development of a variety of angiogenesis
      inhibitors, especially those that target cellular signalling by vascular
      endothelial growth factor-A (VEGF-A), the most potent angiogenic factor known.
      These inhibitors have received lots of attention because they effectively inhibit
      tumour growth in pre-clinical models. However, in clinical trials these same
      inhibitors showed very poor anti-tumour activity. In this review we discuss this
      discrepancy, and we show that the tumour microenvironment is crucial to the
      sensitivity of tumours to anti-angiogenic therapy.

PMID- 16439307
TI  - The organization of the keratin I and II gene clusters in placental mammals and
      marsupials show a striking similarity.
AB  - The genomic database for a marsupial, the opossum Monodelphis domestica, is
      highly advanced. This allowed a complete analysis of the keratin I and keratin II
      gene cluster with some 30 genes in each cluster as well as a comparison with the
      human keratin clusters. Human and marsupial keratin gene clusters have an
      astonishingly similar organization. As placental mammals and marsupials are
      sister groups a corresponding organization is also expected for the archetype
      mammal. Since hair is a mammalian acquisition the following features of the
      cluster refer to its origin. In both clusters hair keratin genes arose at an
      interior position. While we do not know from which epithelial keratin genes the
      first hair keratins type-I and -II genes evolved, subsequent gene duplications
      gave rise to a subdomain of the clusters with many neighboring hair keratin
      genes. A second subdomain accounts in both clusters for 4 neighboring genes
      encoding the keratins of the inner root sheath (irs) keratins. Finally the hair
      keratin gene subdomain in the type-I gene cluster is interrupted after the second
      gene by a region encoding numerous genes for the high/ultrahigh sulfur hair
      keratin-associated proteins (KAPs). We also propose a tentative synteny relation
      of opossum and human genes based on maximal sequence conservation of the encoded
      keratins. The keratin gene clusters of the opossum seem to lack pseudogenes and
      display a slightly increased number of genes. Opossum keratin genes are usually
      longer than their human counterparts and also show longer intergenic distances.

PMID- 16439308
TI  - The Drosophila melanogaster LEM-domain protein MAN1.
AB  - Here we describe the Drosophila melanogaster LEM-domain protein encoded by the
      annotated gene CG3167 which is the putative ortholog to vertebrate MAN1. MAN1 of
      Drosophila (dMAN1) and vertebrates have the following properties in common.
      Firstly, both molecules are integral membrane proteins of the inner nuclear
      membrane (INM) and share the same structural organization comprising an N
      terminally located LEM motif, two transmembrane domains in the middle of the
      molecule, and a conserved RNA recognition motif in the C-terminal region.
      Secondly, dMAN1 has similar targeting domains as it has been reported for the
      human protein. Thirdly, immunoprecipitations with dMAN1-specific antibodies
      revealed that this Drosophila LEM-domain protein is contained in protein
      complexes together with lamins Dm0 and C. It has been previously shown that human
      MAN1 binds to A- and B-type lamins in vitro. During embryogenesis and early
      larval development LEM-domain proteins dMAN1 and otefin show the same expression
      pattern and are much more abundant in eggs and the first larval instar than in
      later larval stages and young pupae whereas the LEM-domain protein Bocksbeutel is
      uniformly expressed in all developmental stages. dMAN1 is detectable in the
      nuclear envelope of embryonic cells including the pole cells. In mitotic cells of
      embryos at metaphase and anaphase, LEM-domain proteins dMAN1, otefin and
      Bocksbeutel were predominantly localized in the region of the two spindle poles
      whereas the lamin B receptor and lamin Dm0 were more homogeneously distributed.
      Downregulation of dMAN1 by RNA interference (RNAi) in Drosophila cultured Kc167
      cells has no obvious effect on nuclear architecture, viability of RNAi-treated
      cells and the intracellular distribution of the LEM-domain proteins Bocksbeutel
      and otefin. In contrast, the localization of dMAN1, Bocksbeutel and otefin at the
      INM is supported by lamin Dm0. We conclude that the dMAN1 protein is not a
      limiting component of the nuclear architecture in Drosophila cultured cells.

PMID- 16439309
TI  - Retinoic acid induces expression of SLP-76: expression with c-FMS enhances ERK
      activation and retinoic acid-induced differentiation/G0 arrest of HL-60 cells.
AB  - Retinoic acid (RA) is known to cause MAPK signaling which propels G0 arrest and
      myeloid differentiation of HL-60 human myeloblastic leukemia cells. The present
      studies show that RA up-regulated expression of SLP-76 (Src-homology 2 domain
      containing leukocyte-specific phospho-protein of 76 kDa), which became a
      prominent tyrosine-phosphorylated protein in RA-treated cells. SLP-76 is a known
      adaptor molecule associated with T-cell receptor and MAPK signaling. To
      characterize functional effects of SLP-76 expression in RA-induced
      differentiation and G0 arrest, HL-60 cells were stably transfected with SLP-76.
      Expression of SLP-76 had no discernable effect on RA-induced ERK activation,
      subsequent functional differentiation, or the rate of RA-induced G0 arrest. To
      determine the effects of SLP-76 in the presence of a RA-regulated receptor, SLP
      76 was stably transfected into HL-60 cells already overexpressing the colony
      stimulating factor-1 (CSF-1) receptor, c-FMS, from a previous stable
      transfection. SLP-76 now enhanced RA-induced ERK activation, compared to parental
      c-FMS transfectants. It also enhanced RA-induced differentiation, evidenced by
      enhanced paxillin expression, inducible oxidative metabolism and superoxide
      production. RA-induced RB tumor suppressor protein hypophosphorylation was also
      enhanced, as was RA-induced G0 cell cycle arrest. A triple Y to F mutant SLP-76
      known to be a dominant negative in T-cell receptor signaling failed to enhance RA
      induced paxillin expression, but enhanced RA-induced ERK activation,
      differentiation and G0 arrest essentially as well as wild-type SLP-76. Thus, SLP
      76 overexpression in the presence of c-FMS, a RA-induced receptor, had the effect
      of enhancing RA-induced cell differentiation. This is the first indication to our
      knowledge that RA induces the expression of an adapter molecule to facilitate
      induced differentiation via co-operation between c-FMS and SLP-76.

PMID- 16439311
TI  - Assessment of the success of cardiopulmonary resuscitation attempts performed in
      a Turkish university hospital.
AB  - The success rate of cardiopulmonary resuscitation (CPR) may differ from
      institution to institution, even within different sites in the same institution.
      A variety of factors may influence the outcome. In this study, we assessed the
      adequacy of CPR attempts guided by the current standards and aimed to define the
      factors influencing the outcome following in-hospital cardiac arrest. One hundred
      and thirty-four patients who required CPR were studied prospectively. Different
      variables for the CPR performance were recorded using forms designed for this
      study in the light of the guidelines. In these CPR forms various data including
      the demographics, history, monitoring, number, composition and experience of the
      anaesthesiologists, the site of CPR, time of day, the delay before onset of CPR,
      tracheal intubation, duration of arrest, initial rhythm in ECG monitored
      patients, management of CPR, drug administration and reversible causes of cardiac
      arrest were recorded. Our rates of immediate survival, survival at 24 h and
      survival to discharge 49.3%, 28.5% and 13.4%, respectively. The extent of
      monitoring prior to arrest, the attendance of one or more experienced
      anesthesiologists in the CPR team, CPR during office hours, CPR in ICU or
      operating room, early initiation of CPR and tracheal intubation prior to arrest
      were found as the factors increasing discharge survival. We conclude that early
      initiation of CPR with an experienced team in a well-equipped hospital sites
      increases the discharge survival rate following cardiac arrest.

PMID- 16439313
TI  - [Message of the President of the French society of anaesthesiology and intensive
      care medicine].

PMID- 16439315
TI  - Abstracts of the XIIIth Biennial Winter Workshop on Schizophrenia Research,
      Davos, Switzerland, February 4-10, 2006.

PMID- 16439314
TI  - Induction of oral tolerization in CD86 deficient mice: a role for CD86 and B
      cells in the up-regulation of TGF-beta.
AB  - Feeding myelin oligodendrocyte glycoprotein (MOG) followed by immunization
      results in induction of oral tolerance evidenced by the amelioration of
      experimental autoimmune encephalomyelitis (EAE). Oral tolerization is
      characterized by the suppression of Th1 responses and up-regulation of Th2
      responses and TGF-beta. To identify the costimulatory molecules and cell types
      involved in cytokine-mediated suppression we examined wild type mice and mice
      deficient for either CD86 (CD86-/-) or B cells (muMT). Oral tolerance was found
      in CD86-/- mice evidenced by amelioration of disease severity, decreased
      proliferative responses and IFN-gamma production and increased IL-4. TGF-beta was
      not up-regulated in CD86-/- or muMT mice but was increased in wild type mice.
      Analysis of the gut associated lymphoid tissue (GALT) of different mouse strains
      (C57BL/6 and PLJxSJL F1) fed distinct myelin antigens (MOG and myelin basic
      protein, MBP) showed that TGF-beta was increased in wild type mice of both
      strains by 3 days post-immunization and further increased with time. In contrast,
      no up-regulation of TGF-beta was found in the GALT of CD86-/- or muMT mice. These
      results demonstrate that CD86 is not required for oral tolerization and that both
      CD86 and B cells are important for the up-regulation of TGF-beta following oral
      antigen.

PMID- 16439316
TI  - Spectrofluorimetric determination of trace heparin using lomefloxacin-terbium
      probe.
AB  - A new spectrofluorimetric method was developed for determination of trace amount
      of heparin (Hep). Using lomefloxacin (LOM)-terbium ion (Tb3+) as a fluorescent
      probe, in the buffer solution of pH 8.70, Hep can remarkably enhance the
      fluorescence intensity of the LOM-Tb3+ complex at lambda = 545 nm and the
      enhanced fluorescence intensity of Tb3+ ion is in proportion to the concentration
      of Hep. Optimum conditions for the determination of Hep were also investigated.
      The linear range for the determination of Hep was 0.6-2.0 microg/ml and the
      detection limit was 45.22 ng/ml. This method is simple, practical and relatively
      free of interference from coexisting substances and can be successfully applied
      to assess Hep in biological samples. By the Rosenthanl graphic method, the
      association constant of Hep with the probe is 4.56 x 10(4) l/mol and binding
      numbers is 18.2. Moreover, the enhancement mechanism of the fluorescence
      intensity in the LOM-Tb3+ system and the LOM-Tb3+-Hep system have also been
      discussed.

PMID- 16439317
TI  - H-point standard addition method--first derivative spectrophotometry for
      simultaneous determination of palladium and cobalt.
AB  - H-point standard addition method (HPSAM) has been applied for simultaneous
      determination of palladium and cobalt in trace levels, using disodium 1-nitroso-2
      naphthol-3, 6-disulphonate (nitroso-R salt) as a selective chromogenic reagent.
      Palladium and cobalt in the neutral pHs form red color complexes with nitroso-R
      in aqueous solutions and making spectrophotometric monitoring possible.
      Simultaneous determination of palladium and cobalt were performed by HPSAM--first
      derivative spectrophotometry. First derivative signals at the two pairs of
      wavelengths, 523 and 589 nm or 513 and 554 nm were monitored with the addition of
      standard solutions of palladium or cobalt, respectively. The method is able to
      accurately determine palladium/cobalt ratio 1:10 to 15:1 (wt/wt). Accuracy and
      reproducibility of the determination method on the various amounts of palladium
      and cobalt known were evaluated in their binary mixtures. To investigate
      selectivity of the method and to ensure that no serious interferences were
      observed the effects of diverse ions on the determination of palladium and cobalt
      were also studied. The recommended procedure was successfully applied to real and
      synthetic cobalt or palladium alloys, B-complex ampoules, a palladium-charcoal
      mixture and real water matrices.

PMID- 16439318
TI  - Moving up from 3 by 5.

PMID- 16439319
TI  - The Tuskegee study of untreated syphilis revisited.

PMID- 16439320
TI  - Polio eradication and measles immunisation in Nigeria.

PMID- 16439321
TI  - Rapidly progressive soft tissue infections.

PMID- 16439323
TI  - New insights into the antiviral effects of chloroquine.

PMID- 16439324
TI  - Postgraduate training in infectious diseases.

PMID- 16439325
TI  - Meticillin-resistant Staphylococcus aureus in rural Asia.

PMID- 16439326
TI  - Development and evaluation of influenza pandemic vaccines.

PMID- 16439327
TI  - New worlds to explore.

PMID- 16439328
TI  - Vertically acquired paediatric coinfection with HIV and hepatitis C virus.
AB  - Both HIV and hepatitis C virus (HCV) can be transmitted from mother to child
      during pregnancy and delivery. Vertical transmission of HIV and HCV separately is
      most likely from HIV/HCV-coinfected mothers; however, transmission of both
      infections is less frequent. The effect of HCV coinfection on HIV-related disease
      remains unclear; whereas most studies indicate no effect, recent results suggest
      HCV in adults accelerates HIV progression. Little is known about how HIV
      coinfection affects HCV progression in children and the information available is
      based on small numbers of patients. Paediatric HIV treatment is extremely
      successful and it is vital to determine if HCV coinfection alters the
      effectiveness of this treatment. The hepatotoxicity of many HIV therapies and the
      possible negative impact of HCV on this treatment, alongside the interactions and
      contraindications of many HIV and HCV therapies, further limits the choice of
      paediatric treatments for coinfected children. Future research must therefore
      focus on vertically acquired HIV/HCV coinfection to inform treatment trials
      addressing coinfection management.

PMID- 16439329
TI  - The new global map of human brucellosis.
AB  - The epidemiology of human brucellosis, the commonest zoonotic infection
      worldwide, has drastically changed over the past decade because of various
      sanitary, socioeconomic, and political reasons, together with the evolution of
      international travel. Several areas traditionally considered to be endemic--eg,
      France, Israel, and most of Latin America--have achieved control of the disease.
      On the other hand, new foci of human brucellosis have emerged, particularly in
      central Asia, while the situation in certain countries of the Near East (eg,
      Syria) is rapidly worsening. Furthermore, the disease is still present, in
      varying trends, both in European countries and in the USA. Awareness of this new
      global map of human brucellosis will allow for proper interventions from
      international public-health organisations.

PMID- 16439330
TI  - Challenges in the concurrent management of malaria and HIV in pregnancy in sub
      Saharan Africa.
AB  - Approximately one million pregnancies are complicated by both malaria and HIV
      infection in sub-Saharan Africa annually. Both infections have been associated
      with maternal and infant morbidity and mortality. Intermittent preventive
      treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent
      pregnancy-related malaria and its complications. Several different regimens of
      antiretroviral therapy are now available to prevent mother-to-child transmission
      of HIV and/or progression of maternal HIV infection during pregnancy. However, no
      published studies have yet shown whether standard intermittent preventive
      treatment and antiretroviral regimens are medically and operationally compatible
      in pregnancy. We reviewed existing policies regarding prevention and treatment of
      HIV and malaria in pregnancy, as well as published literature on adverse effects
      of antiretrovirals and antimalarials commonly used in pregnancy in developing
      countries, and found that concurrent prescription of sulfadoxine-pyrimethamine,
      co-trimoxazole (trimethoprim-sulfamethoxazole), and antiretroviral agents
      including nevirapine and zidovudine per existing protocols for prevention of
      malaria and vertical HIV transmission may result in adverse drug interactions or
      overlapping, diagnostically challenging drug toxicities. Insecticide-treated
      bednets should be provided for HIV-infected pregnant women at risk for malaria.
      Sulfadoxine-pyrimethamine should be prescribed cautiously in women concurrently
      receiving daily nevirapine and/or zidovudine, and should be avoided in women on
      daily co-trimoxazole. Further research is urgently needed to define safe and
      effective protocols for concurrent management of HIV and malaria in pregnancy,
      and to define appropriate interventions for different populations subject to
      differing levels of malaria transmission and antimalarial drug resistance.

PMID- 16439331
TI  - Pertussis: increasing disease as a consequence of reducing transmission.
AB  - Since the 1980s, the occurrence of pertussis cases in developed countries has
      increased and shifted towards older age groups. This resurgence follows 30 years
      of intense mass vaccination, and has been attributed primarily to three factors:
      (1) more effective diagnosis of the disease, (2) waning of vaccine-induced
      immunity, and (3) loss of vaccine efficacy due to the emergence of new Bordetella
      pertussis strains. Here we develop and analyse a mathematical model to assess the
      plausibility of these hypotheses. We consider that exposure to B pertussis
      through natural infection or vaccination induces an immune response that prevents
      severe disease but does not fully prevent mild infections. We also assume that
      these protective effects are temporary due to waning of immunity. These
      assumptions, describing the mode of action of adaptive immunity, are combined
      with a standard transmission model. Two distinct epidemiological scenarios are
      detected: under low transmission, most infections lead to severe disease; under
      high transmission, mild infections are frequent, boosting clinical immunity and
      maintaining low levels of severe disease. The two behaviours are separated by a
      reinfection threshold in transmission. As a result, the highest incidence of
      severe disease is expected to occur at intermediate transmission intensities-
      near the reinfection threshold--suggesting that pertussis resurgence may be
      induced by a reduction in transmission, independently of vaccination. The model
      is extended to interpret the outcomes of current control measures and explore
      scenarios for future interventions.

PMID- 16439332
TI  - Emphysematous cholecystitis due to Salmonella derby.
AB  - We present the case of a woman with diabetes mellitus who developed symptoms and
      signs consistent with gastroenteritis. After admission for hydration, the patient
      rapidly became critically ill and an abdominal catastrophe was suspected as the
      cause of her deterioration. Computed tomography of her abdomen was done and
      revealed gas in the lumen of the gallbladder consistent with emphysematous
      cholecystitis. She underwent emergent cholecystectomy, which revealed that the
      gallbladder had already ruptured. Blood cultures grew Salmonella derby. After a
      prolonged hospitalisation she eventually recovered and was discharged home.
      Emphysematous cholecystitis, thought to be a variant of acute cholecystitis, is a
      medical and surgical emergency. Diagnosis relies heavily on imaging findings by
      ultrasound or computed tomography since the clinical presentation is often non
      specific. Cholecystectomy remains the treatment of choice in addition to broad
      spectrum antibiotics and other supportive measures.

PMID- 16439333
TI  - The Journal of Cystic Fibrosis: a success story.

PMID- 16439334
TI  - [On a density-dependent model of competition for one resource].
AB  - We use the concept of steady-state characteristic of a population using a single
      limiting resource, in order to discuss the issue of the competition of many
      species for the same resource. The steady-state characteristic is a curve that is
      associated to each species, likely to be determined empirically. Once one knows
      the steady-state characteristics and the dynamic of the renewal of the resource,
      it is possible to predict to some extent the issue of the competition and to give
      sufficient conditions for coexistence.

PMID- 16439335
TI  - Prevalence and distribution of MEFV mutations among Arabs from the Maghreb
      patients suffering from familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive inherited disease
      caused by mutations in MEFV. This disease is characterized by recurrent episodes
      of fever accompanied with topical signs of inflammation. Some patients can
      develop renal amyloidosis. We prospectively investigated MEFV mutations in a
      cohort of 209 unrelated Arab patients from Maghreb (85 Algerians, 87 Moroccans,
      and 37 Tunisians) with a clinical suspicion of FMF. FMF is the main cause of
      periodic fever syndrome in Maghreb. The most frequent MEFV mutations in this
      cohort were M694V and M694I. These mutations account for different proportions of
      the MEFV mutations in Algeria (5%, 80%), Morocco (49%, 37%), and Tunisia (50%,
      25%) patients. M694I mutation is specific to the Arab population from Maghreb.
      Other rare mutations were observed: M680L, M680I, A744S, V726A, and E148Q. We
      estimated the frequency of MEFV mutation carriers among the Arab Maghrebian
      population at around 1%, which is significantly lower than in non-Ashkenazi Jews,
      Armenians or Turks.

PMID- 16439336
TI  - Elevated total and isoenzyme forms of acid phosphatase in falciparum malaria.
AB  - The activities of total serum acid phosphatase (E.C. 3.1.3.2) and of two of its
      isoenzymes, tartrate-resistant acid phosphatase and erythrocyte-specific acid
      phosphatase were measured in 109 adult male and female patients presenting acute
      falciparum malaria infection, and a normal, healthy control group comprised of 82
      subjects. All the three forms of acid phosphatase were found to be significantly
      (p<0.05) higher during infection as compared to their activity in the control
      group. This result suggests that the measurement of acid phosphatase,
      particularly the erythrocyte isoenzyme, in serum could be potentially used as a
      biomarker of acute falciparum malaria infection.

PMID- 16439337
TI  - The effect of hormones on bone growth is mediated through mechanical stress.
AB  - Mechanical stresses play a key role in regulating cell growth and cell
      differentiation. Using mechanical and physiological data available in the
      literature, we are able to construct a growth curve of a child, which we compare
      to the standard curve. It appears likely that the impact of hormones on pubertal
      growth rate sprout followed by growth arrest can be solely explained by increased
      mechanical stresses. The uptake of hormones by the muscles results in increased
      mechanical stress on the chondrocyte before and at the puberty, resulting in a
      peak in growth followed by growth cessation.

PMID- 16439338
TI  - Well known does not mean well studied: morphological and molecular support for
      existence of sibling species in the Javanese gliding frog Rhacophorus reinwardtii
      (Amphibia, Anura).
AB  - Morphological, morphometrical and molecular data support the existence of two
      sibling species in the taxon previously known as Rhacophorus reinwardtii. The two
      species can be distinguished by the coloration pattern of webbing, the size of
      adult specimens and the relative size of various morphometric characters. This
      long and commonly known taxon should be separated into two species. As a
      consequence, the conservation status of the new species Rhacophorus kio n. sp. as
      well as of the redefined species Rhacophorus reinwardtii must be re-evaluated
      and, considering the new distribution data and the particular ecological demands,
      both species should be considered as 'endangered'.

PMID- 16439339
TI  - [Effect of water deficit on the PSII photochemical phases in two olive trees
      varieties].
AB  - The effect of the water deficit, on two olive tree varieties 'Chetoui' and
      'Chemlali' at the level of photosystem II photochemistry (PSII) was studied
      through the following parameters: leaf water potential (Psi(Hb)), quantum yield
      of PSII (PhiPSII), maximum quantum yield of PSII (Phi(max) PSII), electron
      transfer rate (J(T)) and photochemical quenching (qP). The results obtained show
      a reduction in the leaf water potential and a decrease in quantum efficiency of
      PSII. Besides, electron transfer rate and photochemical quenching showed an
      increase in response to water deficit. These modifications present some
      differences according to the variety. These observations are discussed in
      relation to the strategies developed to grow drought-resistant olive trees in
      arid areas.

PMID- 16439340
TI  - How was the French BSE epidemic underestimated?
AB  - In a previous study, we showed that estimates of the BSE epidemic in France were
      censored by cattle mortality and by a lack of diagnosis. Indeed, we estimated
      that 51 300 cattle were infected by the BSE agent between 1987 and 1997, whereas
      only 103 clinical BSE cases were detected by the passive surveillance system up
      to June 2000. The question thus arises as to the part played by each form of
      censorship in this underestimation. Here, using an updated cattle survival
      distribution, we estimated that 44 800 cattle were infected by the BSE agent
      between 1987 and 1997, and that 7100 of them showed clinical signs of BSE up to
      June 2000, showing the low efficiency of the surveillance system. Moreover,
      between 2087 and 5980 'infectious' cattle, with clinical or preclinical BSE,
      entered the human food chain before July 1996, the date of the ban on specified
      bovine offal.

PMID- 16439341
TI  - A reappraisal of the geographical distribution of the genus Pseudouroplectes
      Lourenco (Scorpiones: Buthidae) in Madagascar.
AB  - We review aspects of the distributional patterns of Malagasy scorpions belonging
      to the endemic genus Pseudouroplectes (family Buthidae), restricted to dry
      forests formations in the south and southwest. One species is described here as
      new to science. We propose that the observed distributional pattern of members of
      this genus is not only a consequence of recent ecological features of the
      landscape, but also of historical biogeographical factors associated with the
      antiquity of this scorpion lineage.

PMID- 16439342
TI  - Has the kouprey (Bos sauveli Urbain, 1937) been domesticated in Cambodia?
AB  - The kouprey (Bos sauveli Urbain, 1937) is a very rare bovid species of Cambodia,
      which may be extinct in the wild, as no living specimen has been observed for a
      long time. Here, we describe a complete taxidermy mount, which presents
      astonishing morphological similarities with the kouprey. The animal was mounted
      in 1871 at the National Museum of Natural History in Paris, where it was
      referenced as No. 1871-576. It was deposited at the Natural History Museum of
      Bourges, France, in 1931, where it is still conserved today. To clarify the
      taxonomic status of the specimen of Bourges, DNA was extracted from a piece of
      bone taken on the mandible, and two different fragments of the mitochondrial
      cytochrome b gene were independently amplified and sequenced. The phylogenetic
      analyses show that the specimen of Bourges is robustly associated with the
      holotype of the kouprey, and that both are related to other wild species of Bos
      found in Indochina, i.e., banteng (B. javanicus) and gaur (B. frontalis). Because
      of doubts for sexing the animal, we applied a molecular test based on the PCR
      amplification of a DNA fragment specific to the Y chromosome. The results
      indicate that the specimen of Bourges is a male. The comparisons with male
      kouprey previously described in the literature reveal important differences
      concerning the body size, general coloration and horns. As these differences
      involve phenotypic traits that are strongly selected in case of domestication, we
      suggest that the specimen of Bourges was a domestic ox. This implies therefore
      that the kouprey may have been domesticated in Cambodia, and that several extant
      local races may be directly related to the kouprey.

PMID- 16439343
TI  - Promoting informed choice: evaluating a decision-making tool for family planning
      clients and providers in Mexico.
AB  - CONTEXT: The World Health Organization (WHO) has developed a decision-making tool
      to be used by providers and clients during family planning visits to improve the
      quality of services. It is important to examine the tool's usability and its
      impact on counseling and decision-making processes during family planning
      consultations. METHODS: Thirteen providers in Mexico City were videotaped with
      family planning clients three months before and one month after attending a
      training session on the WHO decision-making tool. The videotapes were coded for
      client-provider communication and eye contact, and decision-making behaviors were
      rated. In-depth interviews and focus group discussions explored clients' and
      providers' opinions of the tool. RESULTS: After providers began using the
      decision-making tool, they gave clients more information on family planning,
      tailored that information more closely to clients' situations and more often
      discussed HIV/AIDS prevention, dual protection and condom use. Client involvement
      in the decision-making process and client active communication increased,
      contributing to a shift from provider-dominated to shared decision making.
      Clients reported that the tool helped them understand the provider's explanations
      and made them feel more comfortable talking and asking questions during
      consultations. After one month of practice with the decision-making tool, most
      providers felt comfortable with it and found it useful; however, they recommended
      some changes to the tool to help engage clients in the decision-making process.
      CONCLUSIONS: The decision-making tool was useful both as a job aid for providers
      and as a decision aid for clients.

PMID- 16439344
TI  - Pharmacists' knowledge and perceptions of emergency contraceptive pills in Soweto
      and the Johannesburg Central Business District, South Africa.
AB  - CONTEXT: In South Africa, emergency contraceptive pills are available directly
      from pharmacies without a prescription, yet few studies have assessed
      pharmacists' knowledge of and attitudes toward the medication. METHODS: In-person
      interviews were conducted with 34 pharmacists practicing in Soweto and the
      Johannesburg Central Business District, from February through April 2003. The
      pharmacists provided data on their knowledge of emergency contraceptive pills and
      their attitudes toward providing the medication to women in specific situations.
      RESULTS: Nearly all pharmacists sold at least one of the two types of dedicated
      emergency contraceptive pills available in South Africa. Although most had
      accurate knowledge about the method's dosing schedule, side effects and
      mechanism(s) of action, more than half erroneously believed that repeated use
      posed health risks. A large majority of pharmacists believed the pills should be
      available to rape victims, to single or married women and to women who had never
      given birth, but almost half did not think the pills should be given to women
      younger than 18, and a fourth said they would not give them to women with a late
      menstrual period. About one-third to half of pharmacists supported advance
      provision of the medication under certain circumstances. Most were willing to
      display promotional materials on emergency contraceptives in their pharmacies.
      CONCLUSIONS: Interventions aimed at educating pharmacists about the benefits of
      emergency contraceptive pills, especially for adolescents, are needed. Government
      and medical authorities should take advantage of pharmacists' willingness to
      display educational materials as a way to increase women's knowledge and use of
      the medication in South Africa.

PMID- 16439345
TI  - Pregnancy intentions among Salvadoran fathers: results from the 2003 National
      Male Reproductive Health Survey.
AB  - CONTEXT: In El Salvador, fathers less commonly say that pregnancies are
      unintended than mothers do. However, men's pregnancy intentions are not
      understood as well as women's. METHODS: Data from 425 fathers participating in
      the 2003 National Male Reproductive Health Survey of El Salvador were analyzed to
      examine their intentions in regard to partners' pregnancies that had ended in a
      live birth in the last five years. They were asked whether they had been trying
      to avoid pregnancy at the time of conception, whether they had been trying to get
      their partner pregnant, how they had felt about the pregnancy and what they
      thought their partner's pregnancy intentions had been. Descriptive analyses were
      based on the most recent pregnancy reported by each man. RESULTS: A quarter of
      the pregnancies had been unintended from the men's perspective--13% had been
      mistimed and 11% had been unwanted. Almost half (46%) of unintended pregnancies
      had been conceived when the father was trying to avoid pregnancy. However, 36% of
      men reporting an unintended pregnancy said they had been happy when they found
      out about it. For 20% of all pregnancies, men perceived that their partner's
      pregnancy intentions differed from their own. CONCLUSIONS: Family planning
      services in El Salvador need improvement, and services and outreach should target
      men. Men's experiences with unintended pregnancies--in particular, contraceptive
      failure and discordance within couples about pregnancy intention--are complex and
      merit further investigation.

PMID- 16439346
TI  - The incidence of induced abortion in Uganda.
AB  - CONTEXT: Although Uganda's law permits induced abortion only to save a woman's
      life, many women obtain abortions, often under unhygienic conditions. Small-scale
      studies suggest that unsafe abortion is an important health problem in Uganda,
      but no national quantitative studies of abortion exist. METHODS: A nationally
      representative survey of 313 health facilities that treat women who have
      postabortion complications and a survey of 53 professionals who are knowledgeable
      about the conditions of abortion provision in Uganda were conducted in 2003.
      Indirect estimation techniques were applied to the data to calculate the number
      of induced abortions performed annually. Abortion rates, abortion ratios and
      unintended pregnancy rates were calculated for the nation and its four major
      regions. Data on contraceptive use and unmet need were obtained from Demographic
      and Health Surveys. RESULTS: Each year, an estimated 297,000 induced abortions
      are performed in Uganda, and nearly 85,000 women are treated for complications.
      Abortions occur at a rate of 54 per 1,000 women aged 15-49 and account for one in
      five pregnancies. The abortion rate is higher than average in the Central region
      (62 per 1,000 women), the country's most urban and economically developed region.
      It is also very high in the Northern region (70 per 1,000). Nationally, about
      half of pregnancies are unintended; 51% of married women aged 15-49 and 12% of
      their unmarried counterparts have an unmet need for effective contraceptives.
      CONCLUSIONS: Unsafe abortion exacts a heavy toll on women in Uganda. To reduce
      unplanned pregnancy and unsafe abortion, and to improve women's health, increased
      access to contraceptive services is needed for all women.

PMID- 16439347
TI  - Gender and relationship differences in condom use among 15-24-year-olds in
      Angola.
AB  - CONTEXT: The sexual behavior of young people in Angola will play a major role in
      the future spread of HIV, yet few young people use condoms consistently, and
      reported rates of condom use are low. It is important to identify determinants of
      condom use among Angolan adolescents and young adults. METHODS: Data for analysis
      came from 1,995 sexually experienced youth aged 15-24 who participated in a 2001
      knowledge, attitudes and practices survey in Luanda, Angola. Logistic regression
      analysis was performed to identify predictors of consistent condom use by gender
      and determinants of condom use at last intercourse by type of relationship.
      RESULTS: For both males and females, consistent condom use was positively
      associated with higher levels of education (odds ratios, 1.7-2.6) and believing
      that condoms did not diminish sexual pleasure (1.8 for both genders). It was
      negatively associated with being married or in a cohabiting relationship (0.1
      0.5). Females who equated condom use with lack of trust were less likely to use
      condoms consistently (0.5), and males who believed that condoms were safe and
      those who had multiple partners were more likely to be consistent users (1.6 and
      1.7, respectively). Urban residence, higher education, being in school and not
      equating condom use with lack of trust were important predictors of use at last
      intercourse in regular and casual relationships, whereas access to condoms was
      the most important factor in spousal relationships (4.5). CONCLUSIONS:
      Intervention programs aimed at less educated, periurban and unemployed young
      people should be part of an effective HIV-prevention strategy. Such programs must
      address misperceptions among youth about condom use and the need for protection
      from HIV and other STIs.

PMID- 16439348
TI  - Four new epoxy taxanes from needles of Taxus cuspidata (Taxaceae).
AB  - Four new epoxy taxoids were isolated from the needles of Taxus cuspidata. Their
      structures were established as 2a,9a-diacetoxy-5a-cinnamoyloxy-11,12-epoxy-10ss
      hydroxytax-4(20)-en-13-one (1), 2a,10ss-diacetoxy-5a-cinnamoyloxy-11,12-epoxy-9a
      hydroxytax-4(20)-en-13-one (2), 2a,9a-diacetoxy-11,12-epoxy-10ss,20-dihydroxytax
      4-en-13-one (3) and 2a,10ss-diacetoxy-11,12-epoxy-9a,20-dihydroxytax-4-en-13-one
      (4) on the basis of spectral analysis including 1H-NMR, 13C-NMR, 1H-1H-COSY,
      HSQC, HMBC and HRFABMS. Compounds 3 and 4 are the first example of 11,12-epoxy
      taxoids with C-4 double bond found in T. cuspidata.

PMID- 16439349
TI  - Identification of triterpenoids in chloroform extract of Agarista mexicana by MS
      and NMR.
AB  - Detailed structural study of the major triterpenoids from chloroform extract of
      Agarista mexicana revealed the presence of new pentacyclic triterpene lactone 3ss
      hydroxy-ursan-28ss, 19ss-olide together with four known compounds, 12-ursene,
      campesterol, stigmasterol, sitosterol. These compounds were isolated by
      chromatography and their structures confirmed by NMR experiments and by MS.

PMID- 16439350
TI  - Iridoid and lignan glycosides from Citharexylum spinosum L.
AB  - From the aerial parts of Citharexylum spinosum L., one new iridoid glucoside, the
      7-ss-O-acetate (1) of lamiide, along with four known iridoid glucosides, lamiide
      (2), lamiidoside (3), duranterectoside C (4), 8-epiloganin (5) and one known
      lignan glucoside (+)-lyonirenisol-3a-O-ss-D-glucopyranoside (6) were isolated.
      The compound structures were established by one- and two-dimensional 1H- and 13C
      NMR as well as by ESI-MS spectra.

PMID- 16439351
TI  - Communication problems in Swedish Mental Health reform.
AB  - In a study on the implementation of the Swedish Mental Health reform in the
      county of Gavleborg in Sweden, attention was called, at an early stage, to the
      need for relevant theories on the nature of the obstacles that slowed down the
      reform process. Data had initially been gathered from interviews with persons
      from all levels of the implementation work. A Grounded Theory (GT) study was
      carried out using these data in order to generate a theory on the nature of the
      obstacles. Two separate analyses were made, one based on data from experts and
      decision makers and the other based on data from consumers and staff. Each of
      these analyses generated a theory with great explanatory and predictive value. In
      a further analysis, it became possible to merge the theories into an expanded
      theory with a greater general validity within the entire field of the Swedish
      Mental Health reform process. The expanded theory states that the psychiatric
      reform in Sweden is slowed down by obstacles preventing the transfer of
      information: 1) between staff in the mental health services and staff in the
      social services; 2) between social services' care givers and consumers. One
      reason for not removing these obstacles is that they serve an important purpose
      for those involved, in terms of preserving group identity, which gives them the
      opportunity to exert influence on their situation and provides room for
      manoeuvring.

PMID- 16439352
TI  - ModifiComb, a new proteomic tool for mapping substoichiometric post-translational
      modifications, finding novel types of modifications, and fingerprinting complex
      protein mixtures.
AB  - A major challenge in proteomics is to fully identify and characterize the post
      translational modification (PTM) patterns present at any given time in cells,
      tissues, and organisms. Here we present a fast and reliable method ("ModifiComb")
      for mapping hundreds types of PTMs at a time, including novel and unexpected
      PTMs. The high mass accuracy of Fourier transform mass spectrometry provides in
      many cases unique elemental composition of the PTM through the difference DeltaM
      between the molecular masses of the modified and unmodified peptides, whereas the
      retention time difference DeltaRT between their elution in reversed-phase liquid
      chromatography provides an additional dimension for PTM identification. Abundant
      sequence information obtained with complementary fragmentation techniques using
      ion-neutral collisions and electron capture often locates the modification to a
      single residue. The (DeltaM, DeltaRT) maps are representative of the proteome and
      its overall modification state and may be used for database-independent organism
      identification, comparative proteomic studies, and biomarker discovery. Examples
      of newly found modifications include +12.000 Da (+C atom) incorporation into
      proline residues of peptides from proline-rich proteins found in human saliva.
      This modification is hypothesized to increase the known activity of the peptide.

PMID- 16439353
TI  - Regulation of neuroendocrine exocytosis by the ARF6 GTPase-activating protein
      GIT1.
AB  - Neuroendocrine cells release hormones and neuropeptides by exocytosis, a highly
      regulated process in which secretory granules fuse with the plasma membrane to
      release their contents in response to a calcium trigger. Using chromaffin and
      PC12 cells, we have recently described that the granule-associated GTPase ARF6
      plays a crucial role in exocytosis by activating phospholipase D1 at the plasma
      membrane and, presumably, promoting the fusion reaction between the two membrane
      bilayers. ARF6 is activated by the nucleotide exchange factor ARNO following
      docking of granules to the plasma membrane. We show here that GIT1, a GTPase
      activating protein stimulating GTP hydrolysis on ARF6, is the second molecular
      partner that turns over the GDP/GTP cycle of ARF6 during cell stimulation.
      Western blot and immunofluorescence experiments indicated that GIT1 is cytosolic
      in resting cells but is recruited to the plasma membrane in stimulated cells,
      where it co-localizes with ARF6 at the granule docking sites. Over-expression of
      wild-type GIT1 inhibits growth hormone secretion from PC12 cells; this inhibitory
      effect was not observed in cells expressing a GIT1 mutant impaired in its ARF
      GTPase-activating protein (GAP) activity or in cells expressing other ARF6-GAPs.
      Conversely reduction of GIT1 by RNA interference increased the exocytotic
      activity. Using a real time assay for individual chromaffin cells, we found that
      microinjection of GIT1 strongly reduced the number of exocytotic events. These
      results provide the first evidence that GIT1 plays a function in calcium
      regulated exocytosis in neuroendocrine cells. We propose that GIT1 represents
      part of the pathway that inactivates ARF6-dependent reactions and thereby
      negatively regulates and/or terminates exocytotic release.

PMID- 16439354
TI  - Function and solution structure of Huwentoxin-X, a specific blocker of N-type
      calcium channels, from the Chinese bird spider Ornithoctonus huwena.
AB  - Huwentoxin-X (HWTX-X) is a novel peptide toxin, purified from the venom of the
      spider Ornithoctonus huwena. It comprises 28 amino acid residues including six
      cysteine residues as disulfide bridges linked in the pattern of I-IV, II-V, and
      III-VI. Its cDNA, determined by rapid amplification of 3' and 5' cDNA ends,
      encodes a 65-residue prepropeptide. HWTX-X shares low sequence homology with
      omega-conotoxins GVIA and MVIIA, two well known blockers of N-type Ca2+ channels.
      Nevertheless, whole cell studies indicate that it can block N-type Ca2+ channels
      in rat dorsal root ganglion cells (IC50 40 nm) and the blockage by HWTX-X is
      completely reversible. The rank order of specificity for N-type Ca2+ channels is
      GVIA approximately HWTX-X > MVIIA. In contrast to GVIA and MVIIA, HWTX-X had no
      detectable effect on the twitch response of rat vas deferens to low frequency
      electrical stimulation, indicating that HWTX-X has different selectivity for
      isoforms of N-type Ca2+ channels, compared with GVIA or MVIIA. A comparison of
      the structures of HWTX-X and GVIA reveals that they not only adopt a common
      structural motif (inhibitor cystine knot), but also have a similar functional
      motif, a binding surface formed by the critical residue Tyr, and several basic
      residues. However, the dissimilarities of their binding surfaces provide some
      insights into their different selectivities for isoforms of N-type Ca2+ channels.

PMID- 16439355
TI  - Protein kinase Calpha-RhoA cross-talk in CCL2-induced alterations in brain
      endothelial permeability.
AB  - Monocyte chemoattractant protein-1 (MCP-1 or CCL2) regulates blood-brain barrier
      permeability by inducing morphological and biochemical alterations in the tight
      junction (TJ) complex between brain endothelial cells. The present study used
      cultured brain endothelial cells to examine the signaling networks involved in
      the redistribution of TJ proteins (occludin, ZO-1, ZO-2, claudin-5) by CCL2. The
      CCL2-induced alterations in the brain endothelial barrier were associated with de
      novo Ser/Thr phosphorylation of occludin, ZO-1, ZO-2, and claudin-5. The
      phosphorylated TJ proteins were redistributed/localized in Triton X-100-soluble
      as well as Triton X-100-insoluble cell fractions. Two protein kinase C (PKC)
      isoforms, PKCalpha and PKCzeta, had a significant impact on this event.
      Inhibition of their activity using dominant negative mutants PKCalpha-DN and
      PKCzeta-DN diminished CCL2 effects on brain endothelial permeability. Previous
      data indicate that Rho/Rho kinase signaling is involved in CCL2 regulation of
      brain endothelial permeability. The interactions between the PKC and Rho/Rho
      kinase pathways were therefore examined. Rho, PKCalpha, and PKCzeta activities
      were knocked down using dominant negative mutants (T17Rho, PKCalpha-DN, and
      PKCzeta-DN, respectively). PKCalpha and Rho, but not PKCzeta and Rho, interacted
      at the level of Rho, with PKCalpha being a downstream target for Rho. Double
      transfection experiments using dominant negative mutants confirmed that this
      interaction is critical for CCL2-induced redistribution of TJ proteins.
      Collectively these data suggest for the first time that CCL2 induces brain
      endothelial hyperpermeability via Rho/PKCalpha signal pathway interactions.

PMID- 16439356
TI  - NMR dynamic studies suggest that allosteric activation regulates ligand binding
      in chicken liver bile acid-binding protein.
AB  - Apo chicken liver bile acid-binding protein has been structurally characterized
      by NMR. The dynamic behavior of the protein in its apo- and holo-forms, complexed
      with chenodeoxycholate, has been determined via (15)N relaxation and steady state
      heteronuclear (15)N((1)H) nuclear Overhauser effect measurements. The dynamic
      parameters were obtained at two pH values (5.6 and 7.0) for the apoprotein and at
      pH 7.0 for the holoprotein, using the model free approach. Relaxation studies,
      performed at three different magnetic fields, revealed a substantial
      conformational flexibility on the microsecond to millisecond time scales, mainly
      localized in the C-terminal face of the beta-barrel. The observed dynamics are
      primarily caused by the protonation/deprotonation of a buried histidine residue,
      His(98), located on this flexible face. A network of polar buried side chains,
      defining a spine going from the E to J strand, is likely to provide the long
      range connectivity needed to communicate motion from His(98) to the EF loop
      region. NMR data are accompanied by molecular dynamics simulations, suggesting
      that His(98) protonation equilibrium is the triggering event for the modulation
      of a functionally important motion, i.e. the opening/closing at the protein open
      end, whereas ligand binding stabilizes one of the preexisting conformations (the
      open form). The results presented here, complemented with an analysis of proteins
      belonging to the intracellular lipid-binding protein family, are consistent with
      a model of allosteric activation governing the binding mechanism. The functional
      role of this mechanism is thoroughly discussed within the framework of the
      mechanism for the enterohepatic circulation of bile acids.

PMID- 16439357
TI  - Nonvisual arrestin oligomerization and cellular localization are regulated by
      inositol hexakisphosphate binding.
AB  - Interactions between arrestins and phosphoinositides have been reported to
      regulate multiple membrane-associated signaling and trafficking events including
      clathrin-mediated endocytosis and light adaptation in Drosophila. Arrestins have
      been proposed to have nuclear and cytosolic functions as well, although the
      ligand dependence of these functions has not been investigated. Here we
      characterize the structural, molecular, and cellular interactions between
      arrestin-2 and inositol hexakisphosphate (inositol 1,2,3,4,5,6-hexakisphosphate
      (IP(6))). The crystal structure of the arrestin-2.IP(6) complex was solved to 2.9
      A with crystal lattice contacts suggesting two sites on a protein monomer
      mediating IP(6) binding. Mutagenesis coupled to isothermal titration calorimetry
      and tritiated IP(6) binding assays confirmed two-site binding with a low affinity
      IP(6)-binding site in the N-domain and a high affinity site in the C-domain.
      Native gel electrophoresis, gel filtration, and analytical ultracentrifugation
      demonstrated the ability of IP(6) to promote arrestin-2 oligomerization via the
      two crystallographically defined ligand-binding locations. In addition, analysis
      in mammalian cells revealed that arrestin-2 not only undergoes homo
      oligomerization, but it can also hetero-oligomerize with arrestin-3 in a manner
      that depends on IP(6)-binding sites. Mutation of either IP(6)-binding site in
      arrestin-2 disrupted oligomerization while interactions with known binding
      partners including clathrin, AP-2, and ERK2 were maintained. Subcellular
      localization studies showed that arrestin-2 oligomers are primarily cytoplasmic,
      whereas arrestin-2 monomers displayed increased nuclear localization. Thus, by
      promoting cytosolic oligomerization, IP(6) binding is proposed to be a negative
      regulator of interactions of arrestin with plasma membrane and nuclear signaling
      proteins.

PMID- 16439358
TI  - The structure of the mammalian signal recognition particle (SRP) receptor as
      prototype for the interaction of small GTPases with Longin domains.
AB  - The eukaryotic signal recognition particle (SRP) and its receptor (SR) play a
      central role in co-translational targeting of secretory and membrane proteins to
      the endoplasmic reticulum. The SR is a heterodimeric complex assembled by the two
      GTPases SRalpha and SRbeta, which is membrane-anchored. Here we present the 2.45
      A structure of mammalian SRbeta in its Mg2+ GTP-bound state in complex with the
      minimal binding domain of SRalpha termed SRX. SRbeta is a member of the Ras
      GTPase superfamily closely related to Arf and Sar1, while SRX belongs to the
      SNARE-like superfamily with a fold also known as longin domain. SRX binds to the
      P loop and the switch regions of SRbeta-GTP. The binding mode and structural
      similarity with other GTPase-effector complexes suggests a co-GAP (GTPase
      activating protein) function for SRX. Comparison with the homologous yeast
      structure and other longin domains reveals a conserved adjustable hydrophobic
      surface within SRX which is of central importance for the SRbeta-GTP:SRX
      interface. A helix swap in SRX results in the formation of a dimer in the crystal
      structure. Based on structural conservation we present the SRbeta-GTP:SRX
      structure as a prototype for conserved interactions in a variety of GTPase
      regulated targeting events occurring at endomembranes.

PMID- 16439359
TI  - CpG sites preferentially methylated by Dnmt3a in vivo.
AB  - Dnmt3a and Dnmt3b are two major de novo DNA methyltransferases essential for
      embryonic development in mammals. It has been shown that Dnmt3a and Dnmt3b have
      distinct substrate preferences for certain genomic loci, including major and
      minor satellite repeats. However, the exact target CpG sites where Dnmt3a and
      Dnmt3b catalyze DNA methylation remains largely unknown. To identify a CpG site
      that is specifically methylated by Dnmt3a or Dnmt3b, we screened methylated
      genomic loci by methylation sensitive restriction fingerprinting using genomic
      DNA from wild-type, Dnmt3a null, Dnmt3b null, and Dnmt3a-Dnmt3b double null ES
      cells. Interestingly, one of the CpG sites was preferentially methylated in wild
      type and Dnmt3b null ES cells but not in Dnmt3a null or Dnmt3a-Dnmt3b double null
      ES cells, suggesting that the site-specific methylation was Dnmt3a-dependent.
      Sequencing results revealed that the isolated CpG site is located within the 1st
      exon of the G isoform of fibroblast growth factor (Fgf-1.G) on mouse chromosome
      18. Exogenous expression of Dnmt3a but not Dnmt3b in the double null ES cells
      restored DNA methylation of this CpG site. When we examined alternative
      transcription initiation sites, we determined that another CpG site in the 5'
      flanking region of the Fgf-1.A isoform was also methylated specifically by
      Dnmt3a. Using chimeric constructs between Dnmt3a and Dnmt3b, we further
      determined that the NH(2)-terminal regulatory domain of Dnmt3a was responsible
      for establishing its substrate specificity. These results indicate that certain
      CpG sites within the Fgf-1 gene locus are preferentially methylated by Dnmt3a but
      not by Dnmt3b. Selective methylation by a specific member of Dnmt3 may therefore
      play a role in the orchestration of gene expression during embryonic development.

PMID- 16439360
TI  - The interleukin-1beta gene is transcribed from a poised promoter architecture in
      monocytes.
AB  - Cytokine transcription is usually regulated by transcription factor binding and
      chromatin remodeling following an inducing signal. By contrast, these data showed
      the interleukin (IL)-1beta promoter assembles into a "poised" structure, as
      evidenced by nuclease accessibility and loss of core histones immediately
      surrounding the transcription start site. Strikingly, these properties do not
      change upon transcriptional activation by lipopolysaccharide. Furthermore,
      association of two key transcriptional activators, PU.1 and C/EBPbeta, is robust
      pre- and post-stimulation indicating the IL-1beta promoter is packaged into a
      nontranscribed but poised promoter architecture in cells capable of rapidly
      inducing IL-1beta. Monocyte stimulation causes recruitment of a third factor, IRF
      4, to the IL-1beta enhancer. PU.1 phosphorylation at a CK2 kinase consensus
      element is required for this recruitment. We showed that CK2 phosphorylates PU.1,
      CK2 inhibitors abrogate IL-1beta induction, and CK2 inducibly associates with the
      IL-1beta enhancer. Taken together, these data indicate a novel two-step mechanism
      for IL-1beta transcription: 1) formation of a poised chromatin architecture, and
      2) phosphorylation of an enhancer-bound factor that recruits other activators. We
      propose that this poised structure may generally characterize rapidly activated
      genes.

PMID- 16439361
TI  - MyD88 adapter-like (Mal) is phosphorylated by Bruton's tyrosine kinase during
      TLR2 and TLR4 signal transduction.
AB  - Members of the Toll-like receptor (TLR) family are essential players in
      activating the host innate immune response against infectious microorganisms. All
      TLRs signal through Toll/interleukin 1 receptor domain-containing adapter
      proteins. MyD88 adapter-like (Mal) is one such adapter that specifically is
      involved in TLR2 and TLR4 signaling. When overexpressed we have found that Mal
      undergoes tyrosine phosphorylation. Three possible phospho-accepting tyrosines
      were identified at positions 86, 106, and 187, and two mutant forms of Mal in
      which tyrosines 86 and 187 were mutated to phenylalanine acted as dominant
      negative inhibitors of NF-kappaB activation by lipopolysaccharide (LPS).
      Activation of THP-1 monocytic cells with the TLR4 agonist LPS and the TLR2
      agonist macrophage-activating lipopeptide-2 induced phosphorylation of Mal on
      tyrosine residues. We found that the Bruton's tyrosine kinase (Btk) inhibitor LFM
      A13 could block the endogenous phosphorylation of Mal on tyrosine in cells
      treated with macrophage-activating lipopeptide-2 or LPS. Furthermore, Btk
      immunoprecipitated from THP-1 cells activated by LPS could phosphorylate Mal. Our
      study therefore provides the first demonstration of the key role of Mal
      phosphorylation on tyrosine during signaling by TLR2 and TLR4 and identifies a
      novel function for Btk as the kinase involved.

PMID- 16439362
TI  - Effects of mutations and truncations on the kinetic behavior of IIAGlc, a
      phosphocarrier and regulatory protein of the phosphoenolpyruvate
      phosphotransferase system of Escherichia coli.
AB  - IIAGlc, a component of the glucose-specific
      phosphoenolpyruvate:phosphotransferase system (PTS) of Escherichia coli, is
      important in regulating carbohydrate metabolism. In Glc uptake, the
      phosphotransfer sequence is: phosphoenolpyruvate --> Enzyme I --> HPr --> IIAGlc 
      -> IICBGlc --> Glc. (HPr is the first phosphocarrier protein of the PTS.) We
      previously reported two classes of IIAGlc mutations that substantially decrease
      the P-transfer rate constants to/from IIAGlc. A mutant of His75 which adjoins the
      active site (His90), (H75Q), was 0.5% as active as wild-type IIAGlc in the
      reversible P-transfer to HPr. Two possible explanations were offered for this
      result: (a) the imidazole ring of His75 is required for charge delocalization and
      (b) H75Q disrupts the hydrogen bond network: Thr73, His75, phospho-His90. The
      present studies directly test the H-bond network hypothesis. Thr73 was replaced
      by Ser, Ala, or Val to eliminate the network. Because the rate constants for
      phosphotransfer to/from HPr were largely unaffected, we conclude that the H-bond
      network hypothesis is not correct. In the second class of mutants, proteolytic
      truncation of seven residues of the IIAGlc N terminus caused a 20-fold reduction
      in phosphotransfer to membrane-bound IICBGlc from Salmonella typhimurium. Here,
      we report the phosphotransfer rates between two genetically constructed N
      terminal truncations of IIAGlc (Delta7 and Delta16) and the proteins IICBGlc and
      IIBGlc (the soluble cytoplasmic domain of IICBGlc). The truncations did not
      significantly affect reversible P-transfer to IIBGlc but substantially decreased
      the rate constants to IICBGlc in E. coli and S. typhimurium membranes. The
      results support the hypothesis (Wang, G., Peterkofsky, A., and Clore, G. M.
      (2000) J. Biol. Chem. 275, 39811-39814) that the N-terminal 18-residue domain
      "docks" IIAGlc to the lipid bilayer of membranes containing IICBGlc.

PMID- 16439363
TI  - Role of early growth response-1 (Egr-1) in interleukin-13-induced inflammation
      and remodeling.
AB  - IL-13 is an important stimulator of inflammation and tissue remodeling at sites
      of Th2 inflammation, which plays a key role in the pathogenesis of a variety of
      human disorders. We hypothesized that the ubiquitous transcription factor, early
      growth response-1 (Egr-1), plays a key role in IL-13-induced tissue responses. To
      test this hypothesis we compared the expression of Egr-1 and related moieties in
      lungs from wild type mice and transgenic mice in which IL-13 was overexpressed in
      a lung-specific fashion. We simultaneously characterized the effects of a null
      mutation of Egr-1 on the tissue effects of transgenic IL-13. These studies
      demonstrate that IL-13 stimulates Egr-1 via an Erk1/2-independent Stat6-dependent
      pathway(s). They also demonstrate that IL-13 is a potent stimulator of eosinophil
      and mononuclear cell-rich inflammation, alveolar remodeling, and tissue fibrosis
      in mice with wild type Egr-1 loci and that these alterations are ameliorated in
      the absence of Egr-1. Lastly, they provide insights into the mechanisms of these
      processes by demonstrating that IL-13 stimulates select CC and CXC chemokines
      (MIP-1alpha/CCL-3, MIP-1beta/CCL-4, MIP-2/CXCL2/3, MCP-1/CCL-2, MCP-2/CCL-8, MCP
      3/CCL-7, MCP-5/CCL-12, KC/CXCL-1, and Lix/CXCL-5), matrix metalloproteinase-9,
      tissue inhibitor of metalloproteinase-1, and apoptosis regulators (caspase-3, -6,
      -8, and -9 and Bax) and activates transforming growth factor-beta1 and pulmonary
      caspases via Egr-1-dependent pathways. These studies demonstrate that Egr-1 plays
      a key role in the pathogenesis of IL-13-induced inflammatory and remodeling
      responses.

PMID- 16439364
TI  - Opposite effects of rho family GTPases on engulfment of apoptotic cells by
      macrophages.
AB  - The efficient engulfment of apoptotic cells by professional or nonprofessional
      phagocytes is critical to maintain mammalian homeostasis. To identify molecules
      involved in the engulfment of apoptotic cells, we established a retrovirus-based
      expression cloning system coupled with the engulfment assay. By screening a cDNA
      library of a mouse macrophage cell line, we identified two small GTPase family
      members (RhoG and Rab5) that enhanced the engulfment of apoptotic cells. By
      examining other small GTPase family members, we found that Rac1 enhanced the
      engulfment of apoptotic cells, whereas RhoA inhibited the process. Accordingly,
      the expression of a dominant-negative form of RhoG or Rac1 in primary macrophage
      cultures severely reduced the ability of the macrophages to engulf apoptotic
      cells, and a dominant-negative form of RhoA enhanced the process. These results
      indicated that the efficient engulfment of apoptotic cells requires the concerted
      action of small GTPase family members. We demonstrated previously that NIH3T3
      cells expressing the alphav beta3 integrin efficiently engulf apoptotic cells in
      the presence of milk fat globule epidermal growth factor 8 via a
      phosphatidylserine-dependent mechanism. The dominant-negative form of RhoG or
      Rac1 inhibited this process, which suggested RhoG and Rac1 are also involved in
      the integrin-mediated engulfment.

PMID- 16439365
TI  - Conformational flexibility of mammalian cytochrome P450 2B4 in binding imidazole
      inhibitors with different ring chemistry and side chains. Solution thermodynamics
      and molecular modeling.
AB  - Recent x-ray structures of cytochrome P450 2B4 (CYP2B4) reveal an open form that
      undergoes a large-scale structural transition to a closed form upon binding to 4
      (4-chlorophenyl)imidazole (4-CPI). Here, we report for the first time a complete
      solution thermodynamic study using isothermal titration calorimetry supported by
      spectroscopic studies to elucidate the conformational flexibility of CYP2B4 in
      binding imidazole inhibitors with different ring chemistry and side chains: 4
      CPI, 1-benzylimidazole (1-BI), 1-CPI, 4-phenylimidazole (4-PI), 1-(2
      (benzyloxy)ethyl)imidazole (BEI), and 1-PI. Each of the inhibitors induced type
      II spectral changes, and IC50 values for enzyme inhibition ranged from 0.1 to 2.4
      microM, following the order 1-BI < 4-CPI < 1-CPI < 4-PI < BEI < 1-PI.
      Calorimetric titrations using monomeric enzyme yielded a 1:1 binding
      stoichiometry, with the associated KD values ranging from 0.3 to 4.8 microM and
      following the same rank order as the IC50 values. Changes in enthalpy at 25
      degrees C ranged from -6.5 to -8.8 kcal mol(-1). The largest difference in
      binding entropy (+5.9 versus -4.1 cal mol(-1) K(-1)) was observed between 4-CPI
      and BEI, respectively, with a 2-fold difference in heat capacity changes (-604
      versus -331 cal mol(-1) K(-1)), which is inferred to result from the reduction of
      apolar surface area of the enzyme ensuing from a conformational change upon 4-CPI
      binding. Accessibility to acrylamide of the only tryptophan (Trp121), which is
      located in helix C, was greatly decreased only in protein bound to 4-CPI. Steric
      restrictions hindered the perfect docking of only BEI to the closed conformation
      of the enzyme. The thermodynamic signature obtained for structurally similar
      inhibitors suggests remarkable plasticity of CYP2B4.

PMID- 16439366
TI  - Docking-based substrate recognition by the catalytic domain of a protein tyrosine
      kinase, C-terminal Src kinase (Csk).
AB  - Protein tyrosine kinases are key enzymes of mammalian signal transduction.
      Substrate specificity is a fundamental property that determines the specificity
      and fidelity of signaling by protein tyrosine kinases. However, how protein
      tyrosine kinases recognize the protein substrates is not well understood. C
      terminal Src kinase (Csk) specifically phosphorylates Src family kinases on a C
      terminal Tyr residue, which down-regulates their activities. We have previously
      determined that Csk recognizes Src using a substrate-docking site away from the
      active site. In the current study, we identified the docking determinants in Src
      recognized by the Csk substrate-docking site and demonstrated an interaction
      between the docking determinants of Src and the Csk substrate-docking site for
      this recognition. A similar mechanism was confirmed for Csk recognition of
      another Src family kinase, Yes. Although both Csk and MAP kinases used docking
      sites for substrate recognition, their docking sites consisted of different
      substructures in the catalytic domain. These results helped establish a docking
      based substrate recognition mechanism for Csk. This model may provide a framework
      for understanding substrate recognition and specificity of other protein tyrosine
      kinases.

PMID- 16439367
TI  - Phosphorylation of the hinge domain of the nuclear hormone receptor LRH-1
      stimulates transactivation.
AB  - The nuclear receptor LRH-1 (NR5A2) functions to regulate expression of a number
      of genes associated with bile acid homeostasis and other liver functions, but
      mechanisms that modulate its activity remain unclear. We have found that
      mitogenic stimuli, including treatment with phorbol myristate (PMA), increase LRH
      1 transactivation. This response maps to the hinge and ligand binding domains of
      LRH-1 and is blocked by the mitogen-activated protein kinase ERK1/2 inhibitor
      U0126. LRH-1 is a phosphoprotein and hinge domain serine residues at 238 and 243
      are required for effective phosphorylation, both in vitro and in cells.
      Preventing phosphorylation of these residues by mutating both to alanine
      decreases PMA-dependent LRH-1 transactivation and mimicking phosphorylation by
      mutation to positively charged aspartate residues increases basal
      transactivation. Although serine phosphorylation of the hinge of SF-1 (NR5A1),
      the closest relative of LRH-1, confers a similar response, the specific targets
      differ in the two closely related orphan receptors. These results define a novel
      pathway for the modulation of LRH-1 transactivation and identify specific LRH-1
      residues as downstream targets of mitogenic stimuli. This pathway may contribute
      to recently described proliferative functions of LRH-1.

PMID- 16439368
TI  - Evidence for displacements of the C-helix by CO ligation and DNA binding to CooA
      revealed by UV resonance Raman spectroscopy.
AB  - The UV and visible resonance Raman spectra are reported for CooA from
      Rhodospirillum rubrum, which is a transcriptional regulator activated by growth
      in a CO atmosphere. CO binding to heme in its sensor domain causes rearrangement
      of its DNA-binding domain, allowing binding of DNA with a specific sequence. The
      sensor and DNA-binding domains are linked by a hinge region that follows a long C
      helix. UV resonance Raman bands arising from Trp-110 in the C-helix revealed
      local movement around Trp-110 upon CO binding. The indole side chain of Trp-110,
      which is exposed to solvent in the CO-free ferrous state, becomes buried in the
      CO-bound state with a slight change in its orientation but maintains a hydrogen
      bond with a water molecule at the indole nitrogen. This is the first experimental
      data supporting a previously proposed model involving displacement of the C-helix
      and heme sliding. The UV resonance Raman spectra for the CooA-DNA complex
      indicated that binding of DNA to CooA induces a further displacement of the C
      helix in the same direction during transition to the complete active
      conformation. The Fe-CO and C-O stretching bands showed frequency shifts upon DNA
      binding, but the Fe-His stretching band did not. Moreover, CO-geminate
      recombination was more efficient in the DNA-bound state. These results suggest
      that the C-helix displacement in the DNA-bound form causes the CO binding pocket
      to narrow and become more negative.

PMID- 16439369
TI  - Structures of the carbohydrate recognition domain of Ca2+-independent cargo
      receptors Emp46p and Emp47p.
AB  - Emp46p and Emp47p are type I membrane proteins, which cycle between the
      endoplasmic reticulum (ER) and the Golgi apparatus by vesicles coated with coat
      protein complexes I and II (COPI and COPII). They are considered to function as
      cargo receptors for exporting N-linked glycoproteins from the ER. We have
      determined crystal structures of the carbohydrate recognition domains (CRDs) of
      Emp46p and Emp47p of Saccharomyces cerevisiae, in the absence and presence of
      metal ions. Both proteins fold as a beta-sandwich, and resemble that of the
      mammalian ortholog, p58/ERGIC-53. However, the nature of metal binding is
      distinct from that of Ca(2+)-dependent p58/ERGIC-53. Interestingly, the CRD of
      Emp46p does not bind Ca(2+) ion but instead binds K(+) ion at the edge of a
      concave beta-sheet whose position is distinct from the corresponding site of the
      Ca(2+) ion in p58/ERGIC-53. Binding of K(+) ion to Emp46p appears essential for
      transport of a subset of glycoproteins because the Y131F mutant of Emp46p, which
      cannot bind K(+) ion fails to rescue the transport in disruptants of EMP46 and
      EMP47 genes. In contrast the CRD of Emp47p binds no metal ions at all.
      Furthermore, the CRD of Emp46p binds to glycoproteins carrying high mannosetype
      glycans and the is promoted by binding not the addition of Ca(2+) or K(+) ion in
      These results suggest that Emp46p can be regarded as a Ca(2+)-independent
      intracellular lectin at the ER exit sites.

PMID- 16439370
TI  - Efficacy and safety of fondaparinux for the prevention of venous thromboembolism
      in older acute medical patients: randomised placebo controlled trial.
AB  - OBJECTIVE: To determine the efficacy and safety of the anticoagulant fondaparinux
      in older acute medical inpatients at moderate to high risk of venous
      thromboembolism. DESIGN: Double blind randomised placebo controlled trial.
      SETTING: 35 centres in eight countries. PARTICIPANTS: 849 medical patients aged
      60 or more admitted to hospital for congestive heart failure, acute respiratory
      illness in the presence of chronic lung disease, or acute infectious or
      inflammatory disease and expected to remain in bed for at least four days.
      INTERVENTIONS: 2.5 mg fondaparinux or placebo subcutaneously once daily for six
      to 14 days. OUTCOME MEASURE: The primary efficacy outcome was venous
      thromboembolism detected by routine bilateral venography along with symptomatic
      venous thromboembolism up to day 15. Secondary outcomes were bleeding and death.
      Patients were followed up at one month. RESULTS: 425 patients in the fondaparinux
      group and 414 patients in the placebo group were evaluable for safety analysis
      (10 were not treated). 644 patients (75.9%) were available for the primary
      efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of
      patients treated with fondaparinux and 10.5% (34/323) of patients given placebo,
      a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%).
      Symptomatic venous thromboembolism occurred in five patients in the placebo group
      and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one
      patient (0.2%) in each group. At the end of follow-up, 14 patients in the
      fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died.
      CONCLUSION: Fondaparinux is effective in the prevention of asymptomatic and
      symptomatic venous thromboembolic events in older acute medical patients. The
      frequency of major bleeding was similar for both fondaparinux and placebo treated
      patients.

PMID- 16439371
TI  - Trends in sexually transmitted infections in general practice 1990-2000:
      population based study using data from the UK general practice research database.
AB  - OBJECTIVE: To describe the contribution of primary care to the diagnosis and
      management of sexually transmitted infections in the United Kingdom, 1990-2000,
      in the context of increasing incidence of infections in genitourinary medicine
      clinics. DESIGN: Population based study. SETTING: UK primary care. PARTICIPANTS:
      Patients registered in the UK general practice research database. MAIN OUTCOME
      MEASURES: Incidence of diagnosed sexually transmitted infections in primary care
      and estimation of the proportion of major such infections diagnosed in primary
      care. RESULTS: An estimated 23.0% of chlamydia cases in women but only 5.3% in
      men were diagnosed and treated in primary care during 1998-2000, along with 49.2%
      cases of non-specific urethritis and urethral discharge in men and 5.7% cases of
      gonorrhoea in women and 2.9% in men. Rates of diagnosis in primary care rose
      substantially in the late 1990s. CONCLUSIONS: A substantial and increasing number
      of sexually transmitted infections are diagnosed and treated in primary care in
      the United Kingdom, with sex ratios differing from those in genitourinary
      medicine clinics. Large numbers of men are treated in primary care for
      presumptive sexually transmitted infections.

PMID- 16439372
TI  - Who benefits from Helicobacter pylori eradication?

PMID- 16439373
TI  - Offering results to research participants.

PMID- 16439374
TI  - Funding the global control of bird flu.

PMID- 16439375
TI  - Sex workers to pay the price.

PMID- 16439376
TI  - Oxygen treatment at home.

PMID- 16439377
TI  - Norwegian researcher admits that his data were faked.

PMID- 16439378
TI  - Many cancer networks are failing to improve services.

PMID- 16439380
TI  - Negative reports of mental health deter people from seeking help.

PMID- 16439381
TI  - US Supreme Court upholds Oregon's Death with Dignity Act.

PMID- 16439382
TI  - NICE recommends drugs for moderate Alzheimer's disease.

PMID- 16439383
TI  - US agency wants to limit lawsuits against drug manufacturers.

PMID- 16439386
TI  - Media's treatment of Roy Meadow was "unfair," says High Court judge.

PMID- 16439387
TI  - Review says oseltamivir and zanamivir should be kept for epidemics of flu.

PMID- 16439395
TI  - Claim that "smart" weapons pose little risk to civilians is "absurd".

PMID- 16439396
TI  - Moralistic campaigns are pushing out AIDS prevention work that is based on
      science, report says.

PMID- 16439397
TI  - Funding of bird flu initiative exceeds expectations.

PMID- 16439399
TI  - Woman loses fight for parents' right to know of abortion advice.

PMID- 16439400
TI  - Venous thromboembolism.

PMID- 16439401
TI  - Impact of a medically supervised safer injection facility on community drug use
      patterns: a before and after study.
AB  - PROBLEM: Illicit use of injected drugs is linked with high rates of HIV infection
      and fatal overdose, as well as community concerns about public drug use.
      Supervised injecting facilities have been proposed as a potential solution, but
      fears have been raised that they might encourage drug use. DESIGN: A before and
      after study. Participants and setting 871 injecting drug users recruited from the
      community in Vancouver, Canada. KEY MEASURES FOR IMPROVEMENT: Rates of relapse
      into injected drug use among former users and of stopping drug use among current
      users. STRATEGIES FOR CHANGE: Local health authorities established the Vancouver
      supervised injecting facility to provide injecting drug users with sterile
      injecting equipment, intervention in the event of overdose, primary health care,
      and referral to external health and social services. EFFECTS OF CHANGE: Analysis
      of periods before and after the facility's opening showed no substantial increase
      in the rate of relapse into injected drug use (17% v 20%) and no substantial
      decrease in the rate of stopping injected drug use (17% v 15%). LESSONS LEARNT:
      Recently reported benefits of supervised injecting facilities on drug users' high
      risk behaviours and on public order do not seem to have been offset by negative
      community impacts.

PMID- 16439402
TI  - Medical treatment of early breast cancer. IV: neoadjuvant treatment.

PMID- 16439404
TI  - Blowing smoke: British American Tobacco's air filtration scheme.

PMID- 16439405
TI  - Developing standards, criteria, and thresholds to assess fitness to practise.

PMID- 16439406
TI  - Criteria, competencies, and confidence tricks.

PMID- 16439407
TI  - Introducing new health interventions: diagnostics is the Cinderella of health
      technology assessment.

PMID- 16439408
TI  - Waiting for radiotherapy: financing increased capacity is a must.

PMID- 16439409
TI  - Waiting for radiotherapy: new initiatives may transform service.

PMID- 16439410
TI  - Gastro-oesophageal reflux disease: posture is important.

PMID- 16439411
TI  - Gastro-oesophageal reflux disease: surgery is an alternative.

PMID- 16439412
TI  - Underfunding of primary care in deprived areas affects everyone.

PMID- 16439413
TI  - Introducing new health interventions: some initial risk taking is essential in
      adopting new surgical technology.

PMID- 16439414
TI  - Incapable patients and the law.

PMID- 16439415
TI  - When to test women for human papillomavirus: take this opportunity to screen for
      anal cancer too.

PMID- 16439416
TI  - When to test women for human papillomavirus: testing is possible without
      increasing colposcopy referral rate.

PMID- 16439417
TI  - Research governance: whose idea is it?

PMID- 16439418
TI  - Research governance: research governance approval is putting people off research.

PMID- 16439419
TI  - Management of Clostridium difficile in NHS trusts.

PMID- 16439421
TI  - Improving cervical cancer prevention in a developing country.
AB  - OBJECTIVE: to enhance the delivery of services, using continuous quality
      improvement, and an outreach strategy. DESIGN AND SETTING: pre and post
      measurements in a Primary Health Care system in El Salvador. Outcome indicators:
      women screened for the first time in their lifetime, unsatisfactory samples,
      turnaround time, and follow-up. INTERVENTION: involvement of policy, service
      provision and community levels in 4 plan-do-study-act cycles, facilitating
      linkages between work processes and a quality control group. RESULTS: 3,408 women
      screened for the first time in their lifetime in 1 year in regular services;
      unsatisfactory samples reduced by 1/2; turnaround time reduced by almost 1/3;
      follow-up increased from 24% (22/90) to 100% (196/196) .146 of the 151 women
      cytologically defined as low and high-grade squamous intraepithelial lesions (L
      HSIL) were confirmed on histology as cervical intraepithelial neoplasia (CIN),
      while 5 showed benign changes. Of the 43 women classified as having high-grade
      squamous intraepithelial lesion on cytology, 36 were diagnosed with CIN2 lesions,
      7 with CIN3 and 2 were confirmed with invasive carcinoma. CONCLUSION:
      improvements in delivery of screening can be made with few additional resources
      in the absence of an organized system. We promoted linkages between detection and
      diagnosis through enhancement of teamwork and functional coordination, which
      improved follow-up rates. We restored links between screening and reading
      processes through minor adjustments, which improved the turnaround time of
      samples. Trained outreach workers created new links between community and health
      services, identifying women who had never been screened before in their lives and
      facilitating their access to regular clinic services.

PMID- 16439420
TI  - Fundal dysaccommodation in functional dyspepsia: head-to-head comparison between
      the barostat and three-dimensional ultrasonographic technique.
AB  - BACKGROUND: Recently, non-invasive techniques such as 3 dimensional
      ultrasonography (3DUS) have been developed to assess gastric wall characteristics
      and to investigate their relationship with upper gastrointestinal sensations. To
      date, no head-to-head comparison has been carried out between the barostat and
      the 3DUS technique. AIM: To compare barostat and 3DUS and to investigate the
      relationship between gastric volumes and sensations in patients with functional
      dyspepsia and in healthy subjects. PATIENTS AND METHODS: Gastric accommodation
      was studied in 15 patients with functional dyspepsia and in 15 healthy subjects
      after ingestion of a liquid nutrient (300 kcal) using barostat and 3DUS in random
      order for 60 min. Proximal gastric relaxation was measured using barostat and
      gastric volume using 3DUS. Change in gastric volume, acquired by 3DUS, was
      expressed as total gastric volume/proximal volume ratio (TGV/PV) and compared
      with changes in barostat volume (fundal accommodation). RESULTS: Patients with
      functional dyspepsia showed a smaller change in proximal gastric volume than
      healthy subjects using barostat (mean (SD) 82 (61) v 205 (79) ml, p<0.01) and
      3DUS (118 (41) v 199 (39) ml, p<0.01). Dysaccommodation of the proximal stomach
      was observed in 7 of 15 (46%) patients using the barostat technique. 10 of 15
      (67%) patients were found to have an abnormal change in proximal gastric volume
      using TGV/PV ratio. At 5 min postprandially, fullness was related to the change
      in distal gastric volume (r = 0.51, p = 0.006) in the 3DUS study, whereas no
      relationship was observed in the barostat study. CONCLUSION: 3DUS is a feasible
      non-invasive technique to measure gastric volumes and shows a distinct overlap
      with barostat data in healthy subjects and patients with functional dyspepsia.
      Fullness relates to distal gastric volumes when assessed by non-invasive 3DUS.

PMID- 16439423
TI  - Concanavalin-A reports agonist-induced conformational changes in the intact GluR6
      kainate receptor.
AB  - The agonist-binding domain of ionotropic glutamate receptors (iGluRs) has
      recently been crystallized as two polypeptide chains with a linker region.
      Although work on the structure of this isolated ligand-binding core has been
      invaluable, there is debate over how it relates to conformations adopted by
      intact receptors. iGluR crystals are proposed to represent the activated state as
      their degree of domain closure correlates well with agonist efficacy. However,
      iGluR crystals exhibit high agonist affinity that more closely matches that of
      desensitized receptors. Consequently, conformations adopted by iGluR crystals may
      represent this state. To test this, we have employed the plant lectin,
      concanavalin-A (Con-A) to report conformational changes elicited by kainate (KA)
      iGluR agonists during desensitization. When GluR6 KA receptors (KARs) were pre
      incubated with Con-A, equilibrium responses evoked by the full agonist, l
      glutamate (l-Glu), increased almost 30-fold. However, in the continued presence
      of l-Glu, Con-A exerted no effect suggesting that it has restricted access to its
      binding sites when the agonist is bound. However, Con-A does not discriminate
      well between agonist-bound or -unbound states with the weak partial agonist,
      domoate. Accessibility experiments with KA were intermediate in nature consistent
      with its equilibrium efficacy at GluR6 KARs. Our results suggest that full and
      partial agonists elicit distinct conformational changes in KARs during
      desensitization. This finding can be reconciled with crystallographic data if the
      agonist-binding domain adopts the same conformation in the activated and
      desensitized states. However, other interpretations are possible suggesting
      future work is required if this issue is to be resolved.

PMID- 16439422
TI  - GABA(A), GABA(C) and glycine receptor-mediated inhibition differentially affects
      light-evoked signalling from mouse retinal rod bipolar cells.
AB  - Rod bipolar cells relay visual signals evoked by dim illumination from the outer
      to the inner retina. GABAergic and glycinergic amacrine cells contact rod bipolar
      cell terminals, where they modulate transmitter release and contribute to the
      receptive field properties of third order neurones. However, it is not known how
      these distinct inhibitory inputs affect rod bipolar cell output and subsequent
      retinal processing. To determine whether GABA(A), GABA(C) and glycine receptors
      made different contributions to light-evoked inhibition, we recorded light-evoked
      inhibitory postsynaptic currents (L-IPSCs) from rod bipolar cells mediated by
      each pharmacologically isolated receptor. All three receptors contributed to L
      IPSCs, but their relative roles differed; GABA(C) receptors transferred
      significantly more charge than GABA(A) and glycine receptors. We determined how
      these distinct inhibitory inputs affected rod bipolar cell output by recording
      light-evoked excitatory postsynaptic currents (L-EPSCs) from postsynaptic AII and
      A17 amacrine cells. Consistent with their relative contributions to L-IPSCs,
      GABA(C) receptor activation most effectively reduced the L-EPSCs, while glycine
      and GABA(A) receptor activation reduced the L-EPSCs to a lesser extent. We also
      found that GABAergic L-IPSCs in rod bipolar cells were limited by GABA(A)
      receptor-mediated inhibition between amacrine cells. We show that GABA(A),
      GABA(C) and glycine receptors mediate functionally distinct inhibition to rod
      bipolar cells, which differentially modulated light-evoked rod bipolar cell
      output. Our findings suggest that modulating the relative proportions of these
      inhibitory inputs could change the characteristics of rod bipolar cell output.

PMID- 16439424
TI  - Effect of satellite cell ablation on low-frequency-stimulated fast-to-slow fibre
      type transitions in rat skeletal muscle.
AB  - The purpose of this study was to determine whether satellite cell ablation within
      rat fast-twitch muscles exposed to chronic low-frequency stimulation (CLFS) would
      limit fast-to-slow fibre-type transitions. Twenty-nine male Wistar rats were
      randomly assigned to one of three groups. Satellite cells of the left tibialis
      anterior were ablated by weekly exposure to a 25 Gy dose of gamma-irradiation
      during 21 days of CLFS (IRR-Stim), whilst a second group received only 21 days of
      CLFS (Stim). A third group received weekly doses of gamma-irradiation (IRR). Non
      irradiated right legs served as internal controls. Continuous infusion of 5-bromo
      2'-deoxyuridine (BrdU) revealed that CLFS induced an 8.0-fold increase in
      satellite cell proliferation over control (mean +/-s.e.m.: 23.9 +/- 1.7 versus
      3.0 +/- 0.5 mm(-2), P < 0.0001) that was abolished by gamma-irradiation. M
      cadherin and myogenin staining were also elevated 7.7- and 3.8-fold (P < 0.0001),
      respectively, in Stim compared with control, indicating increases in quiescent
      and terminally differentiating satellite cells; these increases were abolished by
      gamma-irradiation. Myonuclear content was elevated 3.3-fold (P < 0.0001) in Stim,
      but remained unchanged in IRR-Stim. Immunohistochemical analyses revealed
      attenuation of fast-to-slow fibre-type transitions in IRR-Stim compared with
      Stim. Comparable changes were observed at the protein level by SDS-PAGE. It is
      concluded that although considerable adaptive potential exists within myonuclei,
      satellite cells play a role in facilitating fast-to-slow fibre-type transitions.

PMID- 16439425
TI  - Muscarinic receptor activation tunes mouse stratum oriens interneurones to
      amplify spike reliability.
AB  - Cholinergic activation of hippocampal targets can initiate and sustain network
      oscillations in vivo and in vitro, yet the impact of cholinergic modulation on
      the oscillatory properties of interneurones remains virtually unexplored. Using
      whole cell current clamp recordings in acute hippocampal slices, we investigated
      the influence of muscarinic receptor (mAChR) activation on the oscillatory
      properties of CA1 stratum oriens (SO) interneurones in vitro. In response to
      suprathreshold oscillatory input, mAChR activation increased spike reliability
      and precision, and extended the bandwidth that interneurone firing phase-locked.
      These suprathreshold effects were largest at theta frequencies, indicating that
      mAChR activation tunes active conductances to enhance firing reliability and
      precision to theta frequency input. Muscarinic tuning of the intrinsic
      oscillatory properties of interneurones is a novel mechanism that may be crucial
      for the genesis of the theta rhythm.

PMID- 16439426
TI  - Human TRPC6 expressed in HEK 293 cells forms non-selective cation channels with
      limited Ca2+ permeability.
AB  - TRPC6 is thought to be a Ca(2+)-permeable cation channel activated following
      stimulation of G-protein-coupled membrane receptors linked to phospholipase C
      (PLC). TRPC6 current is also activated by exogenous application of 1-oleoyl
      acetyl-sn-glycerol (OAG) or by inhibiting 1,2-diacylglycerol (DAG) lipase
      activity using RHC80267. In the present study, both OAG and RHC80267 increased
      whole-cell TRPC6 current in cells from a human embryonic kidney cell line (HEK
      293) stably expressing TRPC6, but neither compound increased cytosolic free
      Ca(2+) concentration ([Ca(2+)](i)) when the cells were bathed in high-K(+) buffer
      to hold the membrane potential near 0 mV. These results suggested that TRPC6
      channels have limited Ca(2+) permeability relative to monovalent cation
      permeability and/or that Ca(2+) influx via TRPC6 is greatly attenuated by
      depolarization. To evaluate Ca(2+) permeability, TRPC6 currents were examined in
      extracellular buffer in which Ca(2+) was varied from 0.02 to 20 mm. The results
      were consistent with a pore-permeation model in which Ca(2+) acts primarily as a
      blocking ion and contributes only a small percentage ( approximately 4%) to whole
      cell currents in the presence of extracellular Na(+). Measurement of single-cell
      fura-2 fluorescence during perforated-patch recording of TRPC6 currents showed
      that OAG increased [Ca(2+)](i) 50-100 nm when the membrane potential was clamped
      at between -50 and -80 mV, but had little or no effect if the membrane potential
      was left uncontrolled. These results suggest that in cells exhibiting a high
      input resistance, the primary effect of activating TRPC6 will be membrane
      depolarization. However, in cells able to maintain a hyperpolarized potential
      (e.g. cells with a large inwardly rectifying or Ca(2+)-activated K(+) current),
      activation of TRPC6 will lead to a sustained increase in [Ca(2+)](i). Thus, the
      contribution of TRPC6 current to both the kinetics and magnitude of the Ca(2+)
      response will be cell specific and dependent upon the complement of other channel
      types.

PMID- 16439427
TI  - Motor commands contribute to human position sense.
AB  - The role of afferent inflow and efferent outflow (or command) signals in
      judgements of limb position has been debated for over a century. One way to
      assess this is to check for changes during complete paralysis, with the current
      view being that perceived movements or position changes do not usually accompany
      attempts to contract paralysed muscles. To re-examine this, we asked six naive
      subjects to carry out a simple position-matching task at the wrist. In the
      absence of vision, subjects accurately perceived the position to which their
      right wrist had been moved by the experimenter by matching it with their left
      hand. There was no significant change in perception when position was matched
      during sustained flexion or extension efforts. Then we paralysed and
      anaesthetized the right arm with ischaemia in order to produce a 'phantom' hand.
      The perceived position of the wrist changed by more than 20 deg when subjects
      attempted to flex or extend their hand when it was paralysed and anaesthetized.
      Further studies showed that this illusion was not dependent on the way in which
      the paralysis was produced and that the size of the position illusion increased
      when the level of effort during paralysis increased. These results establish for
      the first time a definitive role for 'outflow' signals in position sense.

PMID- 16439428
TI  - Xanthine oxidase does not contribute to impaired peripheral conduit artery
      endothelium-dependent dilatation with ageing.
AB  - Vascular oxidative stress is the key mechanism involved in the age-related
      decline in endothelium-dependent dilatation (EDD). We tested the hypothesis that
      xanthine oxidase (XO), a major vascular source of reactive oxygen species,
      contributes to the impairment in EDD with ageing. At baseline, brachial artery
      flow-mediated dilatation (FMD) was 55% lower in older (n = 9, 64 +/- 2 years,
      8M/1F, mean +/- S.E.M.) versus young (n = 9, 26 +/- 1 years, 8M/1F) healthy
      adults (3.41 +/- 0.44 versus 7.53 +/- 0.67%, P < 0.001), whereas endothelium
      independent dilatation (EID; sublingual nitroglycerin) did not differ between
      groups. Plasma oxidized low-density lipoprotein (oxi-LDL), a measure of systemic
      oxidative stress, was greater at baseline in the older subjects (58.3 +/- 5.9
      versus 46.8 +/- 2.4 U l(-1), P < 0.05) and inversely correlated with baseline FMD
      (r = - 0.54; P < 0.05). Acute administration of allopurinol, a competitive
      inhibitor of XO, reduced plasma uric acid concentrations similarly in both groups
      (P < 0.001), but did not affect FMD, EID, or oxi-LDL in either group. Vascular
      endothelial protein expression of XO (immunofluorescence) was not different in
      antecubital venous cells from the young and older subjects (0.56 +/- 0.12 versus
      0.68 +/- 0.19 XO intensity/human umbilical vein endothelial cell intensity, P =
      0.49). We conclude that XO does not contribute to oxidative stress-associated
      reductions in peripheral conduit artery EDD with ageing in humans, possibly due
      to an absence of age-associated up-regulation of endothelial XO.

PMID- 16439429
TI  - Effects of exercise-induced arterial hypoxaemia and work rate on diaphragmatic
      fatigue in highly trained endurance athletes.
AB  - Diaphragmatic fatigue occurs in highly trained athletes during exhaustive
      exercise. Since approximately half of them also exhibit exercise-induced arterial
      hypoxaemia (EIAH) during high-intensity exercise, the present study sought to
      test the hypothesis that arterial hypoxaemia contributes to exercise-induced
      diaphragmatic fatigue in this population. Ten cyclists ( : 70.0 +/- 1.6 ml kg(-1)
      min(-1); mean +/-s.e.m.) completed, in a balanced ordering sequence, one normoxic
      (end-exercise arterial O(2) saturation (S(a,O(2))): 92 +/- 1%) and one hyperoxic
      (F(I,O(2)): 0.5% O(2); S(a,O(2)) : 97 +/- 1%) 5 min exercise test at intensities
      equal to 80 +/- 3 and 90 +/- 3% of maximal work rate (WR(max)), respectively,
      producing the same tidal volume (V(T)) and breathing frequency (f) throughout
      exercise. Cervical magnetic stimulation was used to determine reduction in twitch
      transdiaphragmatic pressure (P(di,tw)) during recovery. Hyperoxic exercise at 90%
      WR(max) induced significantly (P= 0.022) greater post-exercise reduction in
      P(di,tw) (15 +/- 2%) than did normoxic exercise at 80% WR(max) (9 +/- 2%),
      despite the similar mean ventilation (123 +/- 8 and 119 +/- 8 l min(-1),
      respectively), breathing pattern (V(T): 2.53 +/- 0.05 and 2.61 +/- 0.05 l, f: 49
      +/- 2 and 46 +/- 2 breaths min(-1), respectively), mean changes in P(di) during
      exercise (37.1 +/- 2.4 and 38.2 +/- 2.8 cmH(2)O, respectively) and end-exercise
      arterial lactate (12.1 +/- 1.4 and 10.8 +/- 1.1 mmol l(-1), respectively). The
      difference found in diaphragmatic fatigue between the hyperoxic (at higher leg
      work rate) and the normoxic (at lower leg work rate) tests suggests that neither
      EIAH nor lactic acidosis per se are likely predominant causative factors in
      diaphragmatic fatigue in this population, at least at the level of S(a,O(2))
      tested. Rather, this result leads us to hypothesize that blood flow competition
      with the legs is an important contributor to diaphragmatic fatigue in heavy
      exercise, assuming that higher leg work required greater leg blood flow.

PMID- 16439430
TI  - Erythrocytes and the regulation of human skeletal muscle blood flow and oxygen
      delivery: role of erythrocyte count and oxygenation state of haemoglobin.
AB  - Blood flow to dynamically contracting myocytes is regulated to match O(2)
      delivery to metabolic demand. The red blood cell (RBC) itself functions as an
      O(2) sensor, contributing to the control of O(2) delivery by releasing the
      vasodilators ATP and S-nitrosohaemoglobin with the offloading of O(2) from the
      haemoglobin molecule. Whether RBC number is sensed remains unknown. To
      investigate the role of RBC number, in isolation and in combination with
      alterations in blood oxygenation, on muscle and systemic perfusion, we measured
      local and central haemodynamics during one-legged knee-extensor exercise (
      approximately 50% peak power) in 10 healthy males under conditions of
      normocythaemia (control), anaemia, anaemia + plasma volume expansion (PVX),
      anaemia + PVX + hypoxia, polycythaemia, polycythaemia + hyperoxia and
      polycythaemia + hypoxia, which changed either RBC count alone or both RBC count
      and oxyhaemoglobin. Leg blood flow (LBF), cardiac output (Q) and vascular
      conductance did not change with either anaemia or polycythaemia alone. However,
      LBF increased with anaemia + PVX (28 +/- 4%) and anaemia + PVX + hypoxia (46 +/-
      6%) and decreased with polycythaemia + hyperoxia (18 +/- 5%). LBF and Q with
      anaemia + PVX + hypoxia (8.0 +/- 0.5 and 15.8 +/- 0.7 l min(-1), respectively)
      equalled those during maximal knee-extensor exercise. Collectively, LBF and
      vascular conductance were intimately related to leg arterial-venous (a-v) O(2)
      difference (r(2)= 0.89-0.93; P < 0.001), suggesting a pivotal role of blood O(2)
      gradients in muscle microcirculatory control. The systemic circulation
      accommodated to the changes in muscle perfusion. Our results indicate that, when
      coping with severe haematological challenges, local regulation of skeletal muscle
      blood flow and O(2) delivery primarily senses alterations in the oxygenation
      state of haemoglobin and, to a lesser extent, alterations in the number of RBCs
      and haemoglobin molecules.

PMID- 16439431
TI  - Synaptic vesicles in rat hippocampal boutons recycle to different pools in a use
      dependent fashion.
AB  - Efficient vesicle membrane recycling at presynaptic terminals is pivotal for
      preventing depletion and maintaining high firing rates in neuronal networks. We
      used a new approach, based on the combination of spectrally different optical
      probes, to investigate how stimulation determines the fate of synaptic vesicles
      after endocytosis. We found that in the small central synapses of rat hippocampal
      neurones low frequency stimulation (40 action potentials at 2 Hz) targets
      vesicles preferentially to vesicle pools that were kinetically faster. Vesicles
      taken up during endocytosis triggered by high frequency stimulation (400 action
      potentials, 20 Hz) were also placed in the back of the release queue. We
      performed a spatial analysis of the recycled vesicles in living hippocampal
      boutons using two spectrally different FM-dyes (FM1-43 and FM5-95). By using
      these consecutively, vesicles endocytosed by either stimulation protocol were
      labelled with a different colour. This revealed that the kinetic arrangement was
      also reflected in the spatial organization of vesicles within the bouton. Next,
      we identified the postsynaptic site of the active zone by transfecting the
      neurones with postsynaptic density protein PSD-95-CFP. The data from these triple
      colour experiments suggest that retrieval after low frequency stimulation keeps
      vesicles in a more confined region closer to the active zone as identified by PSD
      95-CFP expression at the postsynaptic site.

PMID- 16439432
TI  - Antioxidants reverse depression of the hypoxic ventilatory response by
      acetazolamide in man.
AB  - The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and
      stimulatory effects on breathing. In this placebo-controlled double-blind study
      we measured the effect of an intravenous dose (4 mg kg(-1)) of this agent on the
      acute isocapnic hypoxic ventilatory response in 16 healthy volunteers
      (haemoglobin oxygen saturation 83-85%) and examined whether its inhibitory
      effects on this response could be reversed by antioxidants (1 g ascorbic acid
      i.v. and 200 mg alpha-tocopherol p.o.). The subjects were randomly divided into
      an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced
      the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55%
      (P < 0.01), respectively, and abolished the O2-CO2 interaction, i.e. the increase
      in O2 sensitivity with rising Pco2. Antioxidants completely reversed this
      inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the
      reversal was partial. In the placebo group, acetazolamide reduced the normo- and
      hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus
      control in both cases), and also abolished the O2-CO2 interaction. Placebo failed
      to reverse these inhibitory effects of acetazolamide in this group. We
      hypothesize that either an isoform of carbonic anhydrase may be involved in the
      regulation of the redox state in the carotid bodies or that acetazolamide and
      antioxidants exert independent effects on oxygen-sensing cells, in which both
      carbonic anhydrase and potassium channels may be involved. The novel findings of
      this study may have clinical implications, for example with regard to a combined
      use of acetazolamide and antioxidants at high altitude.

PMID- 16439434
TI  - Ca2+-desensitizing hypoxic vasorelaxation: pivotal role for the myosin binding
      subunit of myosin phosphatase (MYPT1) in porcine coronary artery.
AB  - Acute hypoxia dilates most systemic arteries leading to increased tissue
      perfusion. We showed that at high stimulus conditions, porcine coronary artery
      was relaxed by hypoxia without a change in [Ca(2+)](i). This 'Ca(2+)
      desensitizing hypoxic relaxation' was validated in permeabilized porcine coronary
      artery smooth muscle (PCASM) in which hypoxia decreased force and myosin
      regulatory light chain phosphorylation (p-MRLC) despite fixed [Ca(2+)]. Rho
      kinase-dependent phosphorylation of MYPT1 (p-MYPT1) is associated with decreased
      MRLC phosphatase (MLCP) activity, and increased Ca(2+) sensitivity of both p-MRLC
      and force. We tested the hypothesis that hypoxia induces Ca(2+)-desensitizing
      hypoxic relaxation via dephosphorylation of p-MYPT1, consequently increasing MLCP
      activity and thus decreasing p-MRLC. alpha-Toxin-permeabilized PCASM pretreated
      with ATPgammaS did not relax in response to hypoxia. Moreover, when MRLC but not
      MYPT1 was protected from ATPgammaS thiophosphorylation by the MRLC kinase
      inhibitor ML7 (300 mum), hypoxia remained ineffective. In contrast, hypoxic
      relaxation was preserved with further addition of the Rho kinase inhibitor Y27632
      (1 mum), to attenuate thiophosphorylation of MYPT1. Importantly, measurements of
      p-MRLC, and p-MYPT1 at T696 and T853 (human sequence) paralleled that of force.
      We conclude that Ca(2+)-desensitizing hypoxic relaxation requires
      dephosphorylation of p-MYPT1. Moreover, no kinases, other then those inhibited by
      ML7 and Y27632, nor their associated phosphoproteins can be involved in Ca(2+)
      desensitizing hypoxic relaxation.

PMID- 16439433
TI  - Programming placental nutrient transport capacity.
AB  - Many animal studies and human epidemiological findings have shown that impaired
      growth in utero is associated with physiological abnormalities in later life and
      have linked this to tissue programming during suboptimal intrauterine conditions
      at critical periods of development. However, few of these studies have considered
      the contribution of the placenta to the ensuing adult phenotype. In mammals, the
      major determinant of intrauterine growth is the placental nutrient supply, which,
      in turn, depends on the size, morphology, blood supply and transporter abundance
      of the placenta and on synthesis and metabolism of nutrients and hormones by the
      uteroplacental tissues. This review examines the regulation of placental nutrient
      transfer capacity and the potential programming effects of nutrition and
      glucocorticoid over-exposure on placental phenotype with particular emphasis on
      the role of the Igf2 gene in these processes.

PMID- 16439435
TI  - Safety analyses of adalimumab (HUMIRA) in global clinical trials and US
      postmarketing surveillance of patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the safety of adalimumab in global clinical trials and
      postmarketing surveillance among patients with rheumatoid arthritis (RA).
      METHODS: Safety data for adalimumab treated patients from randomised controlled
      trials, open label extensions, and two phase IIIb open label trials were
      analysed. In addition, postmarketing spontaneous reports of adverse events in the
      United States were collected following Food and Drug Administration approval of
      adalimumab on 31 December 2002. RESULTS: As of 15 April 2005, the RA clinical
      trial safety database analysed covered 10,050 patients, representing 12,506
      patient-years (PYs) of adalimumab exposure. The rate of serious infections,
      5.1/100 PYs, was comparable to that reported on 31 August 2002 (4.9/100 PYs), and
      to published reports of RA populations naive to anti-tumour necrosis factor (TNF)
      therapy. Following implementation of tuberculosis (TB) screening in clinical
      trials, the rate of TB decreased. There were 34 cases of TB as of this analysis
      (0.27/100 PYs). The standardised incidence ratio for lymphoma was 3.19 (95% CI
      1.78 to 5.26), consistent with the observed increased incidence in the general RA
      population. As of 30 June 2005, there were an estimated 78 522 PYs of exposure to
      adalimumab in the US postmarketing period. Seventeen TB cases were spontaneously
      reported (0.02/100 PYs) from the US. Rates of other postmarketing events of
      interest, such as congestive heart failure, systemic lupus erythematosus,
      opportunistic infections, blood dyscrasias, lymphomas, and demyelinating disease,
      support observations from clinical trials. CONCLUSION: Analyses of these data
      demonstrate that long term adalimumab treatment is generally safe and well
      tolerated in patients with RA.

PMID- 16439436
TI  - Hippocampal atrophy in systemic lupus erythematosus.
AB  - OBJECTIVES: To determine the frequency and progression of hippocampal atrophy in
      systemic lupus erythematosus (SLE) and the clinical, laboratory and treatment
      features associated with its occurrence. METHODS: 150 patients with SLE and 40
      healthy volunteers were enrolled in our study. A complete clinical, laboratory
      and neurological evaluation was performed. Magnetic resonance imaging was carried
      out using a 2T scanner (Elscint Prestige) and coronal T1-weighted images were
      used for manual volumetric measurements. Atrophy was defined as values <2
      standard deviations from the means of controls. RESULTS: At entry into the study,
      the mean right and left hippocampal volumes of patients were significantly
      smaller than the hippocampal volumes of controls (p<0.001). After the follow-up
      magnetic resonance imaging, a significant progression of reduction in right and
      left hippocampal volumes in patients was observed (p<0.001). At entry, atrophy
      was identified in 43.9% and at follow-up in 66.7% of patients with SLE.
      Hippocampal atrophy was related to disease duration (p<0.001) total
      corticosteroid dose (p = 0.01) and history of central nervous system (CNS)
      manifestations (p = 0.01). Progression of atrophy was associated with cumulative
      corticosteroid dose (p = 0.01) and number of CNS events (p = 0.01). Patients with
      cognitive impairment had more severe hippocampal atrophy than those without.
      CONCLUSION: Disease duration, total corticosteroid dose and greater number of CNS
      manifestations were associated with hippocampal atrophy in patients with SLE. A
      significant progression of hippocampal atrophy related to total corticosteroid
      dose and number of CNS events was observed. Further studies are necessary to
      confirm these findings.

PMID- 16439437
TI  - Intrafamilial segregation analysis of the p.E148Q MEFV allele in familial
      Mediterranean fever.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is the most frequent of the
      recurrent inherited fevers. This autosomal recessive disorder is characterised by
      periodic episodes of fever and serositis that commonly affect the people of Arab,
      Armenian, Sephardic Jewish and Turkish origin. Most of the described MEFV gene
      anomalies responsible for the disease are missense mutations. In the absence of
      any functional test, epidemiological studies or pedigree analyses are the only
      means of proving the deleterious character of these sequence variations. Evidence
      was provided by our recent study using a population-based approach, that the
      p.E148Q allele is probably a benign polymorphism and not a disease-causing
      mutation. Its implication in FMF remains, however, controversial. OBJECTIVE: To
      evaluate the segregation of the p.E148Q MEFV allele with FMF disease by using
      pedigree analysis. PARTICIPANTS: 21 patients and 48 unaffected relatives
      belonging to 18 independent families with FMF. RESULTS: Segregation analysis of
      the p.E148Q allele was compatible with a Mendelian autosomal recessive
      transmission of the disease phenotype in only three families. In 15 of 18
      families, segregation was partly or completely defective. The p.E148Q allele was
      not transmitted to 14 of 19 (74%) affected children. CONCLUSIONS: No evidence of
      preferential transmission of p.E148Q from heterozygous parents to their affected
      offspring was observed. MEFV is not associated with the clinical manifestations
      of several patients carrying this variant. Considering p.E148Q to be a benign
      polymorphism should reduce the possibility of false-positive diagnoses, while
      highlighting genetic heterogeneity in FMF.

PMID- 16439438
TI  - Indications for total hip replacement: comparison of assessments of orthopaedic
      surgeons and referring physicians.
AB  - OBJECTIVES: To analyse differences of opinions on indications for primary total
      hip replacements (THRs) within and between groups of orthopaedic surgeons and the
      physicians who refer patients to them. METHODS: 22 orthopaedic centres in 12
      European countries took part, resulting in a postal survey of 304 orthopaedic
      surgeons and 314 referring physicians. Each participant was asked to state what
      importance different domains (pain, functional impairment, physical examination
      and radiographs) have on their decision to recommend THR and to select the most
      appropriate level of severity of each symptom or sign for recommending THR. In
      addition, the participants were asked to prioritise other personal or
      environmental factors that affect their decision to undertake a THR. RESULTS:
      Rest pain, pain with activity and functional limitations were the most important
      criteria for THR, although range of motion and radiographic changes were of least
      importance. Both similarities and differences were observed within and between
      groups of surgeons and referring physicians in the overall approach to
      indications and the most appropriate level of severity of disease for
      recommending THR. Most surgeons agreed on severity levels in only 4 of 11 items
      and most referring physicians in only one. Between the groups, major differences
      occurred with regard to the importance of activities of daily living and the
      appropriate level of symptoms for THR. In general, compared with surgeons,
      referring physicians reported that the disease needed to be more advanced to
      warrant surgery. CONCLUSION: Currently, no consensus exists on objective
      indication criteria for THR. The observed differences between the gatekeepers
      (referring physicians) and surgeons can lead to variations and perhaps inequities
      in the provision of care.

PMID- 16439439
TI  - Atherosclerosis in Takayasu arteritis.
AB  - OBJECTIVE: Chronic inflammatory diseases such as systemic lupus erythematosus
      (SLE) and rheumatoid arthritis are associated with accelerated atherosclerosis.
      We hypothesised that atherosclerosis may also be increased in Takayasu arteritis.
      METHODS: The frequency of atherosclerotic plaques and the intima-media thickness
      (IMT) were investigated in 30 female patients with Takayasu arteritis (mean age
      (standard deviation), 35.4 (8.0) years), along with 45 sex-matched and age
      matched patients with SLE (37.4 (6.8)) and 50 healthy controls (38.2 (5.7)).
      Plaques were scanned and IMT was measured at both sides of the common carotids,
      carotid bulb, and internal and external carotid arteries by B-mode
      ultrasonography. Traditional risk factors for atherosclerosis were also assessed.
      RESULTS: Most of the atherosclerotic risk factors were comparable between
      patients with Takayasu arteritis and SLE. More atherosclerotic plaques were
      observed among patients with Takayasu arteritis (8/30; 27%) and those with SLE
      (8/45; 18%) than among the healthy controls (1/50; 2%; p = 0.005). Logistic
      regression analyses showed that the presence of a plaque was associated only with
      age in both Takayasu arteritis and SLE (p = 0.04 and 0.02, respectively). The
      mean overall IMT was significantly higher among patients with Takayasu arteritis
      (0.95+/-0.31 mm) than among the patients with SLE (0.58+/-0.10 mm) and the
      healthy controls (0.59+/-0.08 mm; p<0.001). CONCLUSION: Patients with Takayasu
      arteritis have a high rate of atherosclerotic plaques, at least as frequent as
      that observed among patients with SLE.

PMID- 16439441
TI  - Racial or ethnic differences in allele frequencies of single-nucleotide
      polymorphisms in the methylenetetrahydrofolate reductase gene and their influence
      on response to methotrexate in rheumatoid arthritis.
AB  - BACKGROUND: The anti-folate drug methotrexate (MTX) is commonly used to treat
      rheumatoid arthritis. OBJECTIVE: To determine the allele frequencies of five
      common coding single-nucleotide polymorphisms (SNPs) in the
      methylenetetrahydrofolate reductase (MTHFR) gene in African-Americans and
      Caucasians with rheumatoid arthritis and controls to assess whether there are
      differences in allele frequencies among these ethnic or racial groups and whether
      these SNPs differentially affect the efficacy or toxicity of MTX. METHODS: Allele
      frequencies in the 677, 1298 and 3 additional SNPs in the MTHFR coding region in
      223 (193 Caucasians and 30 African-Americans) patients with rheumatoid arthritis
      who previously participated in one of two prospective clinical trials were
      characterised, and genotypes were correlated with the efficacy and toxicity of
      MTX. Another 308 subjects with rheumatoid arthritis who participated in
      observational studies, one group predominantly Caucasian and the other African
      American, as well as 103 normal controls (53 African-Americans and 50 Caucasians)
      were used to characterise allele frequencies of these SNPs and their associated
      haplotypes. RESULTS: Significantly different allele frequencies were seen in
      three of the five SNPs and haplotype frequencies between Caucasians and African
      Americans. Allele frequencies were similar between patients with rheumatoid
      arthritis and controls of the same racial or ethnic group. Frequencies of the
      rs4846051C, 677T and 1298C alleles were 0.33, 0.11 and 0.13, respectively, among
      African-Americans with rheumatoid arthritis. Among Caucasians with rheumatoid
      arthritis, these allele frequencies were 0.08 (p<0.001 compared with African
      Americans with rheumatoid arthritis), 0.30 (p = 0.002) and 0.34 (p<0.001),
      respectively. There was no association between SNP alleles or haplotypes and
      response to MTX as measured by the mean change in the 28-joint Disease Activity
      Score from baseline values. In Caucasians, the 1298 A (major) allele was
      associated with a significant increase in MTX-related adverse events
      characteristic of a recessive genetic effect (odds ratio 15.86, 95% confidence
      interval 1.51 to 167.01; p = 0.021), confirming previous reports. There was an
      association between scores of MTX toxicity and the rs4846051 C allele, and
      haplotypes containing this allele, in African-Americans, but not in Caucasians.
      CONCLUSIONS: : These results, although preliminary, highlight racial or ethnic
      differences in frequencies of common MTHFR SNPs. The MTHFR 1298 A and the
      rs4846051 C alleles were associated with MTX-related adverse events in Caucasians
      and African-Americans, respectively, but these findings should be replicated in
      larger studies. The rs4846051 SNP, which is far more common in African-Americans
      than in Caucasians, can also be proved to be a useful ancestry informative marker
      in future studies on genetic admixture.

PMID- 16439442
TI  - Mannan-binding lectin and complement C4A in Icelandic multicase families with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether low mannan-binding lectin (MBL) and C4A null
      alleles (C4AQ0) are associated with systemic lupus erythematosus (SLE) in
      multicase families with SLE. METHODS: Low MBL level was determined by measuring
      serum levels and by genotyping for mutant structural (B/C/D, designated as 0) and
      promoter (LX) alleles (by real-time polymerase chain reaction). C4AQ0 was
      detected by protein electrophoresis and corroborated with haplotype and genotype
      analysis. In nine Icelandic families, 24 patients with SLE were compared with 83
      first-degree and 23 second-degree relatives without SLE. Twenty four unrelated
      family members and a population group of 330 Icelanders served as controls.
      RESULTS: Overall, the frequency of low MBL genotypes (0/0, LX/0 and wild-type/0)
      tended to be higher in patients with SLE than in their first-degree and second
      degree relatives (p = 0.06), but the frequency was similar in the families and in
      the controls (p = 0.6). The frequency of C4AQ0 was, however, increased in
      patients and their relatives compared with that in the controls (p = 0.04). The
      combination of low MBL genotypes and C4AQ0 was found more often in the patients
      than in their relatives (p = 0.03) and controls (p = 0.02). However, low MBL
      level was observed only in patients and first-degree relatives in five of the
      nine multicase families. In these five families, patients with SLE had low MBL
      genotypes more often (64%) than their first-degree (38%) and second-degree (0%)
      relatives (p = 0.001), and the patients with SLE also had, accordingly, lower MBL
      levels than their relatives (p = 0.001). CONCLUSIONS: These findings indicate
      that low MBL levels can predispose people to SLE and highlight the genetic
      heterogeneity of this disease.

PMID- 16439443
TI  - Expression of transforming growth factor-beta (TGFbeta) and the TGFbeta
      signalling molecule SMAD-2P in spontaneous and instability-induced
      osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte
      formation.
AB  - BACKGROUND: The primary feature of osteoarthritis is cartilage loss. In addition,
      osteophytes can frequently be observed. Transforming growth factor-beta (TGFbeta)
      has been suggested to be associated with protection against cartilage damage and
      new cartilage formation as seen in osteophytes. OBJECTIVE: To study TGFbeta and
      TGFbeta signalling in experimental osteoarthritis to gain insight into the role
      of TGFbeta in cartilage degradation and osteophyte formation during
      osteoarthritis progression. METHODS: Histological sections of murine knee joints
      were stained immunohistochemically for TGFbeta3 and phosphorylated SMAD-2 (SMAD
      2P). Expression patterns were studied in two murine osteoarthritis models,
      representing spontaneous (STR/ort model) and instability-associated
      osteoarthritis (collagenase-induced instability model). RESULTS: TGFbeta3 and
      SMAD-2P staining was increasingly reduced in cartilage during osteoarthritis
      progression in both models. Severely damaged cartilage was negative for TGFbeta3.
      In contrast, bone morphogenetic protein-2 (BMP-2) expression was increased. In
      chondrocyte clusters, preceding osteophyte formation, TGFbeta3 and SMAD-2P were
      strongly expressed. In early osteophytes, TGFbeta3 was found in the outer fibrous
      layer, in the peripheral chondroblasts and in the core. Late osteophytes
      expressed TGFbeta3 only in the fibrous layer. SMAD-2P was found throughout the
      osteophyte at all stages. In the late-stage osteophytes, BMP-2 was strongly
      expressed. CONCLUSION: Data show that lack of TGFbeta3 is associated with
      cartilage damage, suggesting loss of the protective effect of TGFbeta3 during
      osteoarthritis progression. Additionally, our results indicate that TGFbeta3 is
      involved in early osteophyte development, whereas BMP might be involved in late
      osteophyte development.

PMID- 16439444
TI  - The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT):
      results of radiographic analyses after 1 year.
AB  - OBJECTIVE: Infliximab is effective in improving signs and symptoms of joint/skin
      involvement, functional status, and quality of life in patients with psoriatic
      arthritis (PsA). Using IMPACT trial data, we assessed the effect of infliximab
      (IFX) on structural damage in PsA. METHODS: Patients with active PsA were
      randomly assigned to receive placebo (PBO/IFX) or infliximab 5 mg/kg (IFX/IFX) at
      weeks 0, 2, 6, and 14, with the primary endpoint at week 16. The PBO group
      received infliximab loading doses at weeks 16, 18, and 22. Thereafter, all
      patients received infliximab 5 mg/kg every 8 weeks through week 50. Hand/feet
      radiographs were obtained at weeks 0 and 50. Total radiographic scores were
      determined using the PsA modified van der Heijde-Sharp (vdH-S) score. Projected
      annual rate of progression was calculated by dividing x ray score by disease
      duration (years). RESULTS: As reported previously, 65% of infliximab treated
      patients versus 10% of PBO treated patients achieved an ACR20 response at week 16
      (p<0.001). At week 50, 69% of patients achieved an ACR20 response. Radiographs
      (baseline and week 50) were available for 72/104 patients. At baseline, estimated
      mean annual rate of progression was 5.8 modified vdH-S points/year. Mean (median)
      changes from baseline to week 50 in the total modified vdH-S score were -1.95 (
      0.50) for PBO/IFX and -1.52 (-0.50) for IFX/IFX patients (p = NS). At week 50,
      85% and 84% of patients in the PBO/IFX and IFX/IFX groups had no worsening in the
      total modified vdH-S score. CONCLUSION: Infliximab inhibits radiographic
      progression in patients with PsA through week 50.

PMID- 16439445
TI  - Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation
      at the region upstream of GTL2 in human renal cell carcinoma.
AB  - A common deletion at chromosomal arm 14q32 in human renal cell carcinoma (RCC)
      prompted us to explore a tumor suppressor gene (TSG) in this region. We report
      that imprinted DLK1 at 14q32, a regulator of adipocyte differentiation, is a
      candidate TSG in RCCs. DLK1 expression was lost in 39 out of 50 (78%) primary RCC
      tissues, whereas expression of DLK1 was maintained in every normal kidney tissue
      examined. DLK1 was expressed in only one of 15 (7%) RCC-derived cell lines. In
      order to see the biological significance of DLK1 inactivation in RCCs, we tested
      the effect of restoration of DLK1 in RCC cell lines, using a recombinant
      retrovirus containing the gene. Reintroduction of DLK1 into DLK1-null RCC cell
      lines markedly increased anchorage-independent cell death, anoikis and suppressed
      tumor growth in nude mice. We then investigated the underlying mechanisms for
      DLK1 inactivation in RCCs. We found loss of heterozygosity at this region in 12
      out of 50 RCC tissues (24%). To explore the role of epigenetic regulation of DLK1
      inactivation in RCCs, we conducted methylation analysis of the upstream region
      and the gene body of DLK1. We could not find a differentially methylated region
      in either the upstream region or the gene body of DLK1. However, we found that
      gain of methylation upstream of GTL2, a reciprocal imprinted gene for DLK1, is a
      critical epigenetic alteration for the inactivation of DLK1 in RCCs. The present
      data have shown that gain of methylation upstream of the untranslated GTL2 leads
      to pathological downregulation of DLK1 in RCCs.

PMID- 16439446
TI  - Islet endothelial cells and pancreatic beta-cell proliferation: studies in vitro
      and during pregnancy in adult rats.
AB  - The growth of both tumors and nonneoplastic tissues may be influenced by signals
      from the vascular endothelium. In the present investigation we show that purified
      proliferating endothelial cells from pancreatic islets can stimulate beta-cell
      proliferation through secretion of hepatocyte growth factor (HGF). This secretion
      could be induced by soluble signals from the islets, such as vascular endothelial
      growth factor-A (VEGF-A) and insulin. During pregnancy, the pancreatic beta-cells
      display a highly reproducible physiological proliferation. We show that islet
      endothelial cell proliferation precedes beta-cell proliferation in pregnant
      animals. Vascular growth was closely associated with endocrine cell
      proliferation, and prominent expression of HGF was observed in islet endothelium
      on d 15 of pregnancy, i.e. coinciding with the peak of beta-cell proliferation.
      In summary, our results suggest the existence of an endothelial-endocrine axis
      within adult pancreatic islets, which is of importance for adult beta-cell
      proliferation.

PMID- 16439448
TI  - Regulation of osteoblast differentiation: a novel function for fibroblast growth
      factor 8.
AB  - Several members of the fibroblast growth factor (FGF) family have an important
      role in the development of skeletal tissues. FGF-8 is widely expressed in the
      developing skeleton, but its function there has remained unknown. We asked in
      this study whether FGF-8 could have a role in the differentiation of mesenchymal
      stem cells to an osteoblastic lineage. Addition of FGF-8 to mouse bone marrow
      cultures effectively increased initial cell proliferation as well as subsequent
      osteoblast-specific alkaline phosphatase production, bone nodule formation, and
      calcium accumulation if it was added to the cultures at an early stage of
      osteoblastic differentiation. Exogenous FGF-8 also stimulated the proliferation
      of MG63 osteosarcoma cells, which was blocked by a neutralizing antibody to FGF
      8b. In addition, the heparin-binding growth factor fraction of Shionogi 115
      (S115) mouse breast cancer cells, which express and secrete FGF-8 at a very high
      level, had an effect in bone marrow cultures similar to that of exogenous FGF-8.
      Interestingly, experimental nude mouse tumors of S115 cells present ectopic bone
      and cartilage formation as demonstrated by typical histology and expression of
      markers specific for cartilage (type II and IX collagen) and bone (osteocalcin).
      These results demonstrate that FGF-8 effectively predetermines bone marrow cells
      to differentiate to osteoblasts and increases bone formation in vitro. It is
      possible that FGF-8 also stimulates bone formation in vivo. The results suggest
      that FGF-8, which is expressed by a great proportion of malignant breast and
      prostate tumors, may, among other factors, also be involved in the formation of
      osteosclerotic bone metastases.

PMID- 16439447
TI  - Insulin-like growth factor-binding protein (IGFBP)-1, -2, -3, -4, -5, and -6 and
      IGFBP-related protein 1 during rainbow trout postvitellogenesis and oocyte
      maturation: molecular characterization, expression profiles, and hormonal
      regulation.
AB  - In the present study we report the full coding sequence of rainbow trout IGF
      binding protein-1 (IGFBP1), -2, -3, -5, and -6 and IGFBP-related protein-1 (IGFBP
      rP1) mRNAs as well as the partial coding sequence of IGFBP-4 mRNA. To our
      knowledge, this is the first report of IGFBP4, IGFBP6, and IGFBP-rP1 in a
      nonmammalian species. The tissue distribution of all mRNAs was studied, and the
      ovarian expression profiles of IGFBP2 to -6 and IGFBP-rP1 between late
      vitellogenesis and oocyte maturation were characterized. In addition, in vitro
      hormonal regulation by the maturation-inducing steroid 17,20beta-dihydroxy-4
      pregnen-3-one (17,20betaP), gonadotropin, and estradiol were studied. We observed
      that besides IGFBP1, which was only found in liver, IGFBP2 to -6 and IGFPB-rP1
      were expressed in the preovulatory ovary. IGFBP3 was also detected in liver,
      trunk, kidney, skin, and gills, whereas IGFBP2 to -6 and IGFBP-rP1 exhibited a
      wider tissue distribution. In the preovulatory ovary, IGFBP3 was strongly down
      regulated during the postvitellogenesis period, whereas IGFBP5 exhibited a
      limited up-regulation. In addition, IGFBP6 and IGFBP-rP1 were up-regulated during
      oocyte maturation. Hormonal regulation data indicated that all ovarian IGFBPs and
      IGFBP-rP1 transcripts are regulated under gonadotropic stimulation at a
      concentration that induced 100% oocyte maturation. In addition, IGFBP2 to -5
      transcripts are regulated by 17,20betaP and estradiol. Together, our observations
      strongly suggest that during final oocyte maturation, a down-regulation of
      IGFBP3, -4, and -5 occurs in the oocyte in response to gonadotropic and
      17,20betaP (IGFBP3 and -5) stimulation, whereas an up-regulation of IGFBP2 and -6
      occurs in follicular layers or extrafollicular tissue in response to gonadotropic
      stimulation.

PMID- 16439449
TI  - Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in
      adult female, but not male, rats.
AB  - This study aimed to test the hypothesis that the tuberoinfundibular dopaminergic
      neurons of the arcuate nucleus and/or the lactotroph cells of the anterior
      pituitary gland are key targets for the programming effects of perinatal
      glucocorticoids (GCs). Dexamethasone was administered noninvasively to fetal or
      neonatal rats via the mothers' drinking water (1 mug/ml) on embryonic d 16-19 or
      neonatal d 1-7, and control animals received normal drinking water. At 68 d of
      age, the numbers of tyrosine hydroxylase-positive (TH+) cells in the arcuate
      nucleus and morphometric parameters of pituitary lactotrophs were analyzed. In
      control animals, striking sex differences in TH+ cell numbers, lactotroph cell
      size, and pituitary prolactin content were observed. Both pre- and neonatal GC
      treatment regimens were without effect in adult male rats, but in females, the
      overriding effect was to abolish the sex differences by reducing arcuate TH+ cell
      numbers (pre- and neonatal treatments) and reducing lactotroph cell size and
      pituitary prolactin content (prenatal treatment only) without changing lactotroph
      cell numbers. Changes in circulating prolactin levels represented a net effect of
      hypothalamic and pituitary alterations that exhibited independent critical
      windows of susceptibility to perinatal GC treatments. The dopaminergic neurons of
      the hypothalamic periventricular nucleus and the pituitary somatotroph
      populations were not significantly affected by either treatment regimen in either
      sex. These data show that the adult female hypothalamo-lactotroph axis is
      profoundly affected by perinatal exposure to GCs, which disrupts the tonic
      inhibitory tuberoinfundibular dopaminergic pathway and changes lactotroph
      morphology and prolactin levels in the pituitary and circulation. These findings
      provide new evidence for a long-term disruption in prolactin-dependent
      homeostasis in females, but not males, after inappropriate GC exposure in
      perinatal life.

PMID- 16439450
TI  - Endoplasmic reticulum aminopeptidase-1 mediates leukemia inhibitory factor
      induced cell surface human leukocyte antigen-G expression in JEG-3
      choriocarcinoma cells.
AB  - Maternal immune tolerance is required for extravillous trophoblasts (EVTs) to
      invade the decidua without rejection. Endoplasmic reticulum aminopeptidase-1
      (ERAP1) generates human leukocyte antigen (HLA) class I-adapted antigenic
      peptides, but its function in trophoblasts lacking classical HLA class I
      molecules remains undetermined. Leukemia inhibitory factor (LIF) is produced from
      decidua during the implantation period and plays a necessary role in establishing
      pregnancy. This study is intended to investigate the location and the function of
      ERAP1 in trophoblastic cells, focusing on LIF. Immunohistochemistry showed strong
      ERAP1 expression in cultured EVTs. In choriocarcinoma cell lines used as a model
      for trophoblasts, ERAP1 was expressed more intensively in JEG-3 than BeWo cells.
      Immunoblot analysis and immunocytochemistry localized ERAP1 to the endoplasmic
      reticulum (ER) in JEG-3 cells. Flow cytometry with HLA-G antibody to monitor the
      supply of antigenic peptides presenting to HLA-G in the ER showed that reducing
      ERAP1 transcripts by RNA interference did not affect cell surface expression of
      membrane HLA-G1 (mHLA-G1) in JEG-3 cells under basal conditions. In LIF-treated
      JEG-3 cells, cell surface mHLA-G1 expression was increased along with ERAP1
      protein and promoter activities. In contrast to nonstimulated cells, eliminating
      ERAP1 from LIF-treated JEG-3 cells reduced the cell surface mHLA-G1 expression
      and soluble HLA-G1 secretion. This study provides the first evidence showing that
      ERAP1 is localized in the ER of trophoblasts and is involved in regulating cell
      surface HLA-G expression in the presence of LIF. Consequently, ERAP1 would
      function to present antigenic peptides to HLA-G in trophoblasts.

PMID- 16439451
TI  - Circadian Clock mutation in dams disrupts nursing behavior and growth of pups.
AB  - To understand the role of the circadian molecular clock in mouse reproduction, we
      investigated the daily rhythms associated with nursing and pup growth in Clock
      mutant mice maintained under light-dark housing conditions. The daily rhythm
      associated with the maternal behavior of crouching had a strong diurnal peak and
      two weak nocturnal peaks in wild-type dams, whereas homozygotes (Clock/Clock)
      exhibited no significant peaks in activity. Wild-type, but not Clock-mutant, dams
      showed high, rhythmic levels of prolactin content in serum that corresponded with
      crouching. Pup body weight increased at a significantly slower rate in Clock
      mutant dams compared with wild-type dams under all experimental conditions when
      the pups ranged from 10-15 in number. Heterozygote dams equally bred wild-type,
      heterozygote, or homozygote pups. The amount of milk secreted from dams, as
      calculated by the increase in pup body weight through suckling, was lower in
      Clock-mutant mothers vs. wild-type mice. When Clock-mutant dams gave birth to
      more than 10 pups, survival was poor for offspring until the time of weaning. The
      present results demonstrate that Clock mutation disrupts daily maternal behavior
      and the growth and survival rate of pups, especially with the breeding of more
      than 10 pups.

PMID- 16439452
TI  - Regulation of spontaneous contractile activity in the bovine epididymal duct by
      cyclic guanosine 5'-monophosphate-dependent pathways.
AB  - Passage of spermatozoa through the epididymis is obligatory for sperm maturation
      processes and is based on spontaneous phasic contractions (SC) of the epididymal
      duct. Here, the functional role of cyclic GMP (cGMP) signaling in modulating SC
      in the bovine epididymal caput and corpus region was examined by muscle tension
      recording and immunological and autoradiographic techniques. The cGMP-analog 8
      bromo (Br)-cGMP, as well as the nitric oxide (NO) donor sodium nitroprusside and
      the natriuretic peptides (NPs) atrial NP and C-type NP, displayed distally
      increasing SC-relaxant effects. In agreement, a distally increasing epididymal
      expression of the cGMP-dependent protein kinase I (PKG I), endothelial NO
      synthase (eNOS), and the atrial NP receptor was found. Immunoreactivity for PKG,
      soluble guanylate cyclase, and eNOS could be localized to the epididymal muscle
      cells as well as to the epithelial basal cells only at the corpus level. The SC
      relevant action of NO and the NPs was cGMP dependent, and the action of 8-Br
      cGMP, in turn, was modified by epithelial and luminal factors. The NOS inhibitor
      L-NAME (N(omega)-nitro-L-arginine methyl ester) caused an increase in SC
      frequency, indicating basal activity of NO generating enzymes. The SC-inhibitory
      effect of 8-Br-cGMP was clearly reduced by the PKG inhibitor Rp-8-Br-cGMPS as
      well as by iberiotoxin, thapsigargin, and indomethacin, pointing to PKG as main
      SC-relevant target of cGMP, and to large-conductance calcium-activated K(+)
      channels, the sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase and cyclooxygenase
      1 as possible targets of PKG. These data support an essential role of cGMP
      signaling in the control of epididymal peristalsis, thereby enabling fine tuning
      of sperm transport and maturation.

PMID- 16439454
TI  - Ligand-independent effects of estrogen receptor beta on mouse gonadotropin
      releasing hormone promoter activity.
AB  - GnRH is the most upstream regulator of reproduction in vertebrates, and its
      synthesis and release are regulated by gonadal steroid hormones. The proposed
      sites of hormone action were historically thought to be upstream from GnRH
      neurons; however, the discovery of ERbeta in a subset of GnRH neurons suggests
      that this hypothesis should be reevaluated. To determine a functional role for
      ERbeta in GnRH neurons, we examined ERbeta's regulation of GnRH promoter
      activity. The GnRH-producing cell line, GT1-7, was cotransfected with expression
      vectors containing one of three ERbeta splice variants and a luciferase-reporter
      construct containing the full-length mouse GnRH promoter sequence or one of two
      deletions upstream of the transcription start site (-225/-201; -184/-150).
      Transfected cells were treated with 100 nm 17beta-estradiol (E(2)),
      diarylpropionitrile, raloxifene, or vehicle. There was a robust increase in GnRH
      luciferase activity by all ERbeta splice variants in the absence of hormone.
      Furthermore, E(2) treatment abolished this response for ER-beta1 and ER-beta2,
      but not ER-beta1delta3. The -225/-201 and -184/-150 regions were critical for
      ERbeta-induced promoter activity because deletion of these regions eliminated the
      ligand-independent effects of ERbeta. ER-beta1 binds directly to these promoter
      regions and because there are no classical estrogen response elements in the
      mouse GnRH promoter, these data raise the possibility that this region contains a
      novel estrogen response element specific for ERbeta. Overall, our data suggest
      that ERbeta functions as a basic transcription factor in GnRH neurons and
      demonstrate a potential molecular mechanism for the negative feedback effects of
      E(2) on GnRH.

PMID- 16439453
TI  - Estradiol reduces nonclassical transcription at cyclic adenosine 3',5'
      monophosphate response elements in glioma cells expressing estrogen receptor
      alpha.
AB  - Estradiol can protect the brain from a variety of insults by activating membrane
      initiated signaling pathways, and thereby modulate gene expression and lead to
      functional changes in neurons. These direct neuronal effects of the hormone have
      been well documented; however, it is less understood what effects estradiol may
      have on nonneuronal cells of the central nervous system. There is evidence that
      estradiol levels can induce the release of glial-derived growth factors and other
      cytokines, suggesting that estradiol may both directly and indirectly protect
      neurons. To determine whether 17beta-estradiol (E2) can activate rapid signaling
      and modulate nonclassical transcription in astrocytes, we stably transfected the
      C6 rat glioblastoma cell line with human estrogen receptor (ER) alpha (C6ERalpha)
      or rat ERbeta (C6ERbeta). Introduction of a cAMP response element-luciferase
      reporter gene into C6, C6ERalpha, and C6ERbeta cells leads to the observation
      that E2 treatment reduced isoproterenol-stimulated luciferase activity by 35% in
      C6ERalpha but had no effect on reporter gene expression in C6ERbeta or
      untransfected C6 cells. A similar effect was seen with a membrane-impermeable
      estrogen (E2-BSA), suggesting the modulation of nonclassical transcription by
      estradiol treatment is mediated by the activation of a membrane-initiated
      signaling pathway. Furthermore, pretreatment with wortmannin
      (phosphatidylinsositol 3-kinase) or U73122 (phospholipase C) attenuated the E2
      induced reduction in nonclassical transcription. We conclude that E2 treatment
      reduces cAMP response element-mediated transcription in glioma cells expressing
      ERalpha and that this reduction is dependent on the activation of membrane
      initiated signaling. These findings suggest a novel model of estrogen rapid
      signaling in astrocytes that leads to modulation of nonclassical transcription.

PMID- 16439455
TI  - Adrenocorticotropin-dependent changes in SF-1/DAX-1 ratio influence steroidogenic
      genes expression in a novel model of glucocorticoid-producing adrenocortical cell
      lines derived from targeted tumorigenesis.
AB  - We established the first adrenocortical tumor cell lines with complete zona
      fasciculata (ZF) cell phenotype from tumors induced in transgenic mice by large T
      antigen of simian virus 40 under the control of the aldose reductase-like akr1b7
      gene promoter. Adrenocortical tumor cell lines produced high amounts of
      corticosterone and were responsive to ACTH. All genes that are supportive for
      glucocorticoid synthesis including cyp21a1 and cyp11b1 were expressed, and most
      of them were transiently up-regulated by ACTH at transcriptional level:
      stimulation culminated after 3-6 h and returned to basal levels after 24 h.
      Taking advantage of these cells, we have examined the effect of ACTH on DAX-1
      (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on X
      chromosome, gene 1) and SF-1 (steroidogenic factor 1), two transcription factors
      known to respectively repress and activate adrenocortical steroidogenesis by
      acting on common target genes. According to their antagonistic activities, DAX-1
      mRNA and protein levels were transiently down-regulated by ACTH, whereas those of
      SF-1 were stimulated, with kinetics paralleling those of steroidogenic genes
      expression, notably of two known SF-1 target genes, star and akr1b7. This
      suggests an essential role of SF-1/DAX-1 proteins ratio to achieve proper ACTH
      control of steroidogenic gene expression in cells derived from ZF. This was
      confirmed in mice adrenals, where repression of dax-1 gene and concomitant up
      regulation of sf-1, star, and akr1b7 genes were observed in response to ACTH
      stimulation. In conclusion, using both unique differentiated cell lines and in
      vivo approaches, we provide the first evidence that hormonally induced changes in
      SF-1/DAX-1 ratio are part of the molecular arsenal of ZF cells to fine tune ACTH
      responsiveness.

PMID- 16439456
TI  - Spironolactone preserves cardiac norepinephrine reuptake in salt-sensitive Dahl
      rats.
AB  - An impairment of cardiac norepinephrine (NE) reuptake via the neuronal NE
      transporter (NET) enhances the effects of increased cardiac NE release in heart
      failure patients. Increasing evidence suggests that aldosterone and endothelins
      promote sympathetic overstimulation of failing hearts. Salt-sensitive Dahl rats
      (DS) fed a high-salt diet developed arterial hypertension and diastolic heart
      failure as well as elevated plasma levels of endothelin-1 and NE. Cardiac NE
      reuptake and NET-binding sites, as assessed by clearance of bolus-injected
      [(3)H]NE in isolated perfused rat hearts and [(3)H]mazindol binding, were
      reduced. Treatment of DS with the mineralocorticoid receptor antagonist
      spironolactone preserved the plasma levels of endothelin-1 and NE, cardiac NE
      reuptake, and myocardial NET density. Moreover, the ventricular function and
      survival of spironolactone-treated DS were significantly improved compared with
      untreated DS. The alpha(1)-inhibitor prazosin decreased blood pressure in DS
      similar to spironolactone treatment, but did not normalize the plasma levels of
      endothelin-1 and NE, NE reuptake, or ventricular function. In a heart failure
      independent model, Wistar rats that were infused with aldosterone and fed a high
      salt diet developed impaired cardiac NE reuptake. Treatment of these rats with
      the endothelin A receptor antagonist darusentan attenuated the impairment of NE
      reuptake. In conclusion, spironolactone preserves NET-dependent cardiac NE
      reuptake in salt-dependent heart failure. Evidence is provided that aldosterone
      inhibits NET function through an interaction with the endothelin system.
      Selective antagonism of the mineralocorticoid and/or the endothelin A receptor
      might represent therapeutic principles to prevent cardiac sympathetic
      overactivity in salt-dependent heart failure.

PMID- 16439457
TI  - Identification of a signaling pathway involving progesterone receptor,
      calcitonin, and tissue tranglutaminase in Ishikawa endometrial cells.
AB  - Previous studies indicated that calcitonin (CT), a peptide hormone involved in
      calcium (Ca(2+)) homeostasis, is transiently induced by steroid hormone
      progesterone (P) in the uterine epithelia of the rat and human within the window
      of implantation. Targeted disruption of uterine CT expression markedly impaired
      implantation in the rat. To gain insight into the molecular events underlying CT
      action in the endometrium, we performed gene expression profiling in response to
      CT in a human endometrial adenocarcinoma cell line, Ishikawa. We identified the
      gene encoding tissue tranglutaminase type II (tTGase), which participates in
      Ca(2+)-dependent, protein-protein cross-linking, as a downstream target of CT.
      Interestingly, addition of P alone to Ishikawa cells led to a marked induction in
      the level of both CT and tTGase, indicating the existence of a pathway involving
      P receptors, CT, and tTGase in these cells. Other studies revealed that
      regulation of the tTGase gene by CT occurs via its cell surface receptor and uses
      both cAMP and Ca(2+) signaling pathways. We also noted that tTGase protein is
      expressed in human endometrium during the P-dominated midsecretory phase of the
      menstrual cycle, and it is localized at the basal membrane of glandular
      epithelium and the surrounding stroma. The spatio-temporal expression of tTGase
      in human endometrium during the cycle closely overlapped with that of CT. In
      summary, we have uncovered a novel steroid-regulated signaling cascade in which P
      induces CT, which, in turn, induces tTGase and potentially plays a critical role
      in the human endometrium during implantation.

PMID- 16439458
TI  - Gonadal steroid modulation of stress-induced hypothalamo-pituitary-adrenal
      activity and anxiety behavior: role of central oxytocin.
AB  - Intracerebroventricular administration of oxytocin reduces anxiety behavior and
      hypothalamo-pituitary-adrenal (HPA) responses to stress in female rats. Similar
      changes are seen in late-pregnant rats, and oxytocin-sensitive pathways may
      mediate these effects. This study investigated anxiety behavior and stress
      responses using a gonadal steroid model of late pregnancy, which is known to
      increase endogenous oxytocin expression. Compared with continuous progesterone
      treatment, 3-d withdrawal of progesterone after 11-d treatment of ovariectomized
      rats with estradiol and progesterone resulted in increased binding of the
      oxytocin receptor ligand [(125)I]d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr
      NH(2)(9)]ornithine vasotocin in selective forebrain regions, including the
      ventrolateral septum and ventromedial hypothalamus. Behavior in the elevated plus
      maze indicated that progesterone withdrawal had an anxiolytic effect, and this
      was associated with lower levels of c-fos mRNA expression in the ventral
      hippocampus, an area previously shown to be sensitive to oxytocin. In other
      groups of animals, the plasma corticosterone response to a psychological stress
      (10 min of 114 dB white noise) was significantly attenuated by this steroid
      manipulation. Furthermore, simultaneous infusion of the selective oxytocin
      receptor antagonist desGlyNH(2), d(CH(2))(5)[Tyr(Me)(2),Thr(4)]OVT during the
      period of progesterone withdrawal reversed this attenuation of noise-induced HPA
      activation, indicating a role for endogenous oxytocin in this effect. Thus,
      mimicking the steroid profile of late pregnancy leads to a reduction in anxiety
      behavior and attenuates HPA activity induced by mild stress. These effects appear
      to be mediated through the involvement of central oxytocin neurotransmission.

PMID- 16439459
TI  - Regulation of Graves' hyperthyroidism with naturally occurring CD4+CD25+
      regulatory T cells in a mouse model.
AB  - Graves' hyperthyroidism can be efficiently induced in susceptible mouse strains
      by repeated immunization with recombinant adenovirus coding the TSH receptor
      (TSHR). This study was designed to evaluate the role(s) played by naturally
      occurring CD4(+)CD25(+) regulatory T cells in the development of Graves'
      hyperthyroidism in resistant C57BL/6 and susceptible BALB/c mice. Depletion of
      CD4(+)CD25(+) T cells rendered some C57BL/6 mice susceptible to induction of
      hyperthyroidism. Thus, hyperthyroidism developed in 30% of the CD4(+)CD25(+) T
      cell-depleted C57BL/6 mice immunized with adenovirus expressing the TSHR A
      subunit (AdTSHR289) vs. 0% of those immunized with AdTSHR289 alone. This
      immunological manipulation also enhanced disease severity in susceptible BALB/c
      mice, as reflected by a significant increase in mean T(4) levels by CD4(+)CD25(+)
      T cell depletion. The immunoenhancing effect of CD4(+)CD25(+) T cell depletion
      appears to be attributable to an increase in thyroid-stimulating antibody
      production and/or a decrease in thyroid-blocking antibody synthesis, but not
      immune deviation to either T helper 1 or 2 cells. Interestingly, unlike BALB/c
      mice, some hyperthyroid C57BL/6 mice showed some intrathyroidal lymphocytic
      infiltration with follicular destruction. These results indicate that
      CD4(+)CD25(+) T cells play a role in disease susceptibility and severity in
      adenovirus-TSHR-induced Graves' hyperthyroidism. Overall, the imbalance between
      effector and regulatory T cells appears to be crucial in the pathogenesis of
      Graves' disease.

PMID- 16439460
TI  - Disruption of gap junctional communication within the ovarian follicle induces
      oocyte maturation.
AB  - Meiotically arrested mammalian oocytes are stimulated to resume meiosis by LH.
      This response, which can be reversed by elevation of intraoocyte cAMP levels, is
      associated with interruption of gap junctional communication (GJC) within the
      ovarian follicle. In the present study, we examined the hypothesis that
      disruption of GJC within the ovarian follicle is sufficient for induction of
      oocyte maturation. For this purpose, we incubated rat follicle-enclosed oocytes
      with carbenoxolone (CBX), a known blocker of gap junctions. We found that this
      selective disruptor of GJC promoted maturation of almost all the follicle
      enclosed oocytes after 5 h of incubation; this response was also obtained by a
      transient (2 h) exposure to this agent. CBX-induced oocyte maturation was
      accompanied by a substantial decrease in intraoocyte concentrations of cAMP that
      was not associated with elevated activity of type 3A phosphodiesterase (PDE3A).
      The effect of CBX on reinitiation of meiosis was blocked by
      isobutylmethylxanthine, a phosphodiesterase inhibitor. Unlike LH, CBX did not
      activate MAPK in the follicular cells, and inhibition of the MAPK signaling
      pathway by means of UO126 did not prevent the resumption of meiosis. Injection of
      CBX into the ovarian bursa of intact animals stimulated maturation in 30% of the
      oocytes, whereas no maturation was observed in the contralateral ovary injected
      with PBS. We conclude that, because experimentally induced breakdown of
      communication within the ovarian follicle is associated with a drop in
      intraoocyte cAMP concentrations and results in resumption of meiosis, this could
      be the physiological mechanism employed by LH to stimulate oocyte maturation.

PMID- 16439461
TI  - Monocyte chemotactic protein-1 is a potential player in the negative cross-talk
      between adipose tissue and skeletal muscle.
AB  - Adipose tissue is a major secretory and endocrine active organ producing a
      variety of bioactive proteins that may regulate energy metabolism and insulin
      sensitivity. In several studies, we have already shown that adipocyte-secretory
      products induce skeletal muscle insulin resistance. However, the precise nature
      of these factors has remained elusive. Human adipocytes were found to secrete
      various cytokines including IL-6, IL-8, macrophage inflammatory protein
      1alpha/beta, and monocyte chemotactic protein-1 (MCP-1). Among these candidates,
      MCP-1 alone impaired insulin signaling in skeletal muscle cells at doses similar
      to its physiological plasma concentrations (200 pg/ml), whereas IL-6, IL-8, and
      macrophage inflammatory protein-1beta were effective at very high concentrations
      only. In addition, MCP-1 significantly reduced insulin-stimulated glucose uptake
      in the myocytes. Expression analysis of chemokine receptors in skeletal muscle
      cells revealed the presence of chemokine CXC motif receptor 1/2 and chemokine CC
      motif receptor 1/2/4/5/10. The action of MCP-1 on insulin signaling in skeletal
      muscle cells occurs via ERK1/2 activation but does not involve activation of the
      nuclear factor kappaB pathway. In conclusion, our data show that adipocytes
      secrete various adipokines that may be involved in the negative cross-talk
      between adipose tissue and skeletal muscle. Human skeletal muscle cells are
      highly sensitive toward MCP-1, which impairs insulin signaling and glucose uptake
      at concentrations even below that found in the circulation. However, other
      cytokines that are released by adipocytes impair insulin action only at
      supraphysiological concentrations. Therefore, MCP-1 may represent a molecular
      link in the negative cross-talk between adipose tissue and skeletal muscle
      assigning a completely novel important role to MCP-1 besides inflammation.

PMID- 16439463
TI  - Hydrocortisone and purinergic signaling stimulate sodium/iodide symporter (NIS)
      mediated iodide transport in breast cancer cells.
AB  - The sodium/iodide symporter (NIS) mediates a remarkably effective targeted
      radioiodide therapy in thyroid cancer; this approach is an emerging candidate for
      treating other cancers that express NIS, whether endogenously or by exogenous
      gene transfer. Thus far, the only extrathyroidal malignancy known to express
      functional NIS endogenously is breast cancer. Therapeutic efficacy in thyroid
      cancer requires that radioiodide uptake be maximized in tumor cells by
      manipulating well-known regulatory factors of NIS expression in thyroid cells,
      such as TSH, which stimulates NIS expression via cAMP. Similarly, therapeutic
      efficacy in breast cancer will likely depend on manipulating NIS regulation in
      mammary cells, which differs from that in the thyroid. Human breast
      adenocarcinoma MCF-7 cells modestly express endogenous NIS when treated with all
      trans-retinoic acid (tRa). We report here that hydrocortisone and ATP each
      markedly stimulates tRa-induced NIS protein expression and plasma membrane
      targeting in MCF-7 cells, leading to at least a 100% increase in iodide uptake.
      Surprisingly, the adenyl cyclase activator forskolin, which promotes NIS
      expression in thyroid cells, markedly decreases tRa-induced NIS protein
      expression in MCF-7 cells. Isobutylmethylxanthine increases tRa-induced NIS
      expression in MCF-7 cells, probably through a purinergic signaling system
      independent of isobutylmethylxanthine's action as a phosphodiesterase inhibitor.
      We also observed that neither iodide, which at high concentrations down-regulates
      NIS in the thyroid, nor cAMP has a significant effect on NIS expression in MCF-7
      cells. Our findings may open new strategies for breast-selective pharmacological
      modulation of functional NIS expression, thus improving the feasibility of using
      radioiodide to effectively treat breast cancer.

PMID- 16439462
TI  - Androgen effects on hippocampal CA1 spine synapse numbers are retained in Tfm
      male rats with defective androgen receptors.
AB  - The effects of estradiol benzoate (EB), dihydrotestosterone (DHT), or the
      antiandrogen hydroxyflutamide on CA1 pyramidal cell dendritic spine synapses were
      investigated in adult male rats. To elucidate the contribution of the androgen
      receptor to the hormone-induced increase in hippocampal CA1 synapses, wild-type
      males were compared with males expressing the Tfm mutation, which results in
      synthesis of defective androgen receptors. Orchidectomized rats were treated with
      EB (10 microg/rat.d), DHT (500 mug/rat.d), hydroxyflutamide (5 mg/rat.d), or the
      sesame oil vehicle sc daily for 2 d and examined using quantitative electron
      microscopic stereological techniques, 48 h after the second injection. In wild
      type males, DHT and hydroxyflutamide both induced increases in the number of
      spine synapses in the CA1 stratum radiatum, whereas EB had no effect. DHT almost
      doubled the number of synaptic contacts observed, whereas hydroxyflutamide
      increased synapse density by approximately 50%, compared with the vehicle
      injected controls. Surprisingly, in Tfm males, the effects of EB, DHT, and
      hydroxyflutamide were all indistinguishable from those observed in wild-type
      animals. These observations demonstrate that Tfm male rats resemble normal males
      in having no detectable hippocampal synaptic response to a dose of EB that is
      highly effective in females. Despite the reduction in androgen sensitivity as a
      result of the Tfm mutation, hippocampal synaptic responses to both DHT and a
      mixed androgen agonist/antagonist (hydroxyflutamide) remain intact in Tfm males.
      These data are consistent with previous results suggesting that androgen effects
      on hippocampal spine synapses may involve novel androgen response mechanisms.

PMID- 16439464
TI  - Twenty-four-hour rhythmic gene expression in the rhesus macaque adrenal gland.
AB  - The suprachiasmatic nucleus plays a key role in the circadian secretion of
      adrenocortical hormones. However, there is evidence from mouse studies that
      components of the circadian clock are also expressed within the adrenal gland
      itself. In the present study we performed genome-wide expression profiling to
      determine whether the adrenal gland of rhesus monkeys shows temporal gene
      expression across a 24-h period. We identified 322 transcripts with rhythmic
      patterns of expression and found that the phase distribution of cycling
      transcripts varied across the day, with more genes showing activation during the
      night. We classified the transcripts by their function and clustered them
      according to their participation in common biochemical pathways: 1) catecholamine
      synthesis and reuptake; 2) cholesterol cleavage and dehydroepiandrosterone
      sulfate synthesis; 3) protein synthesis and turnover; and 4) the circadian clock
      mechanism. In an additional experiment, we assessed the expression of various
      clock genes at two time points, 12 h apart. We found that expression of Bmal1 and
      Cry1 was higher at 1300 h, or zeitgeber time 6, whereas expression of Per1 was
      higher at 0100 h (zeitgeber time 18). Expression levels of Rev-erbalpha were
      higher at 0100 h than at 1300 h (P<0.05), and immunohistochemistry revealed a
      strong expression of this transcription factor specifically in chromaffin cells
      of the adrenal medulla. Taken together, the data indicate that the primate
      adrenal gland shows rhythmic expression of genes associated with cell biology and
      synthesis of steroids and catecholamines. Moreover, they strongly imply the
      existence of an intrinsic circadian clock.

PMID- 16439465
TI  - Receptor-interacting protein 140 differentially regulates estrogen receptor
      related receptor transactivation depending on target genes.
AB  - We have investigated the effects of receptor-interacting protein 140 (RIP140) on
      transcriptional regulation by estrogen receptor-related receptors (ERRs). We
      first show that RIP140 inhibits transactivation by ERRalpha, beta, and gamma on
      natural or artificial reporter genes containing different types of response
      elements. This repression correlates with a strong in vitro binding between
      several regions of RIP140 and the three ERR isoforms. Surprisingly, although
      RIP140 inhibits transactivation of the thyroid hormone receptor-alpha gene by
      ERRbeta, it significantly increases its regulation by ERRalpha and ERRgamma.
      Mutagenesis and transient transfections in SL2 cells indicate that thyroid
      hormone receptor-alpha promoter expression involved Sp1 sites. In support of this
      observation, we demonstrate that RIP140 also positively regulates ERRs
      transactivation of other known Sp1 targets such as the p21 gene. This effect
      requires the two proximal Sp1 binding sites of the promoter and is partially
      dependent on the activation function 2 domain of ERRs. Finally, we provide
      evidences for a role of histone deacetylases in the regulation of p21 promoter by
      RIP140. Altogether, these data indicate that RIP140 differentially regulates ERR
      activity depending on the target sequence on the promoters.

PMID- 16439466
TI  - HCl-induced inflammatory mediators in cat esophageal mucosa and inflammatory
      mediators in esophageal circular muscle in an in vitro model of esophagitis.
AB  - Platelet-activating factor (PAF) and interleukin-6 (IL-6) are produced in the
      esophagus in response to HCl and affect ACh release, causing changes in
      esophageal motor function similar to esophagitis (Cheng L, Cao W, Fiocchi C,
      Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289:
      G418-G428, 2005). We therefore examined HCl-activated mechanisms for production
      of PAF and IL-6 in cat esophageal mucosa and circular muscle. A segment of normal
      mucosa was tied at both ends, forming a mucosal sac (Cheng L, Cao W, Fiocchi C,
      Behar J, Biancani P, and Harnett KM. Am J Physiol Gastrointest Liver Physiol 289:
      G860-G869, 2005) that was filled with acidic Krebs buffer (pH 5.8) or normal
      Krebs buffer (pH 7.0) as control and kept in oxygenated Krebs buffer for 3 h. The
      supernatant of the acidic sac (MS-HCl) abolished contraction of normal muscle
      strips in response to electric field stimulation. The inhibition was reversed by
      the PAF antagonist CV3988 and by IL-6 antibodies. PAF and IL-6 levels in MS-HCl
      and mucosa were significantly elevated over control. IL-6 levels in mucosa and
      supernatant were reduced by CV3988, suggesting that formation of IL-6 depends on
      PAF. PAF-receptor mRNA levels were not detected by RT-PCR in normal mucosa, but
      were significantly elevated after exposure to HCl, indicating that HCl causes
      production of PAF and expression of PAF receptors in esophageal mucosa and that
      PAF causes production of IL-6. PAF and IL-6, produced in the mucosa, are released
      to affect the circular muscle layer. In the circular muscle, PAF causes
      production of additional IL-6 that activates NADPH oxidase to induce production
      of H(2)O(2). H(2)O(2) causes formation of IL-1beta that may induce production of
      PAF in the muscle, possibly closing a self-sustaining cycle of production of
      inflammatory mediators.

PMID- 16439467
TI  - Differential expression proteomics of human colon cancer.
AB  - The focus of this study was to use differential protein expression to investigate
      operative pathways in early stages of human colon cancer. Colorectal cancer
      represents an ideal model system to study the development and progression of
      human tumors, and the proteomic approach avoids overlooking posttranslational
      modifications not detected by microarray analyses and the limited correlation
      between transcript and protein levels. Colon cancer samples, confined to the
      intestinal wall, were analyzed by expression proteomics and compared with matched
      samples from normal colon tissue. Samples were processed by two-dimensional gel
      electrophoresis, and spots differentially expressed and consistent across all
      patients were identified by matrix-assisted laser desorption ionization-time-of
      flight mass spectrometry analyses and by Western blot analyses. After
      differentially expressed proteins and their metabolic pathways were analyzed, the
      following main conclusions were achieved for tumor tissue: 1) a shift from beta
      oxidation, as the main source of energy, to anaerobic glycolysis was observed
      owed to the alteration of nuclear- versus mitochondrial-encoded proteins and
      other proteins related to fatty acid and carbohydrate metabolism; 2) lower
      capacity for Na(+) and K(+) cycling; and 3) operativity of the apoptosis pathway,
      especially the mitochondrial one. This study of the human colon cancer proteome
      represents a step toward a better understanding of the metabolomics of colon
      cancer at early stages confined to the intestinal wall.

PMID- 16439468
TI  - Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin
      and negatively associates with Crohn's disease.
AB  - Crohn's disease (CD) is associated with elevated adaptive immunity to commensal
      microbes, with flagellin being a dominant antigen. In light of heightened
      awareness of the importance of innate immunity in regulating adaptive immunity
      and ambiguity as to the role of CD-associated immune responses in CD
      pathophysiology, we sought to determine whether natural acquisition of immune
      responses to flagellin were regulated by the innate immune flagellin receptor
      toll-like receptor 5 (TLR5) and determine whether persons carrying a recently
      defined common dominant-negative TLR5 polymorphism (TLR5-stop) might be protected
      from developing CD. Carriage rates of a recently defined dominant-negative TLR5
      polymorphism (TLR5-stop) and levels of serum immunoreactivity to bacterial
      products were measured in inflammatory bowel disease patients, first-degree
      relatives, and unrelated controls. We observed that, in healthy subjects, persons
      carrying TLR5-stop had significantly lower levels of flagellin-specific IgG and
      IgA but had similar levels of total and LPS-specific Ig. Moreover, we observed
      that, among Jewish subjects, the carriage rate of TLR5-stop (in heterozygous
      state) was significantly less in CD patients, but not ulcerative colitis (UC)
      patients, compared with unaffected relatives and unrelated controls (5.4, 0.9,
      6.0, and 6.5% for unaffected relatives, CD, UC, and unrelated Jewish controls,
      respectively, n = 296, 215, 185, and 416, respectively; P = 0.037 by likelihood
      calculation for CD vs. controls), indicating that TLR5-stop can protect persons
      of Jewish ethnicity against CD. We did not observe a significant association of
      TLR5-stop with CD in a non-Jewish cohort (11.1, 10.4, and 11.7% for unaffected
      relatives, CD, and UC, respectively; n = 841, 543, and 300 for unaffected
      relatives, respectively). These results demonstrate that natural acquisition of
      immune responses to flagellin are regulated by TLR5 and suggest that immune
      responses to flagellin are not merely associated with CD but rather promote the
      pathogenic response.

PMID- 16439469
TI  - Increased apoptosis and accelerated epithelial migration following inhibition of
      hedgehog signaling in adaptive small bowel postresection.
AB  - The intestinal epithelium undergoes a marked adaptive response following loss of
      functional small bowel surface area characterized by increased crypt cell
      proliferation and increased enterocyte migration from crypt to villus tip,
      resulting in villus hyperplasia and enhanced nutrient absorption. Hedgehog (Hh)
      signaling plays a critical role in regulating epithelial-mesenchymal interactions
      during morphogenesis of the embryonic intestine. Our previous studies showed that
      blocking Hh signaling in neonatal mice results in increased small intestinal
      epithelial crypt cell proliferation and altered enterocyte fat absorption and
      morphology. Hh family members are also expressed in the adult intestine, but
      their role in the mature small bowel is unclear. With the use of a model of
      intestinal adaptation following partial small bowel resection, the role of Hh
      signaling in the adult gut was examined by determining the effects of blocking Hh
      signaling on the regenerative response following loss of functional surface area.
      Hh-inactivating monoclonal antibodies or control antibodies were administered to
      mice that sustained a 50% intestinal resection. mRNA analyses of the preoperative
      ileum by quantitative real-time PCR revealed that Indian hedgehog was the most
      abundant Hh family member. The Hh receptor Patched was more abundant than Patched
      2. Analyses of downstream targets of Hh signaling demonstrated that Gli3 was
      twofold more abundant than Gli1 and Gli2 and that bone morphogenetic protein
      (BMP)2 was most highly expressed compared with BMP1, -4, and -7. Following
      intestinal resection, the expression of Hh, Patched, Gli, and most BMP genes was
      markedly downregulated in the remnant ileum, and, in anti-Hh antibody-treated
      mice, expression of Patched 2 and Gli 1 was further suppressed. In Hh antibody
      treated mice following resection, the enterocyte migration rate from crypt to
      villus tip was increased, and by 2 wk postoperation, apoptosis was increased in
      the adaptive gut. However, crypt cell proliferation, villus height, and crypt
      depth were not augmented. These data indicate that Hh signaling plays a role in
      adult gut epithelial homeostasis by regulating epithelial cell migration from
      crypt to villus tip and by enhancing apoptosis.

PMID- 16439470
TI  - LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in
      mice.
AB  - Although it is clear that bile acid accumulation is the major initiator of
      fibrosis caused by cholestatic liver disease, endotoxemia is a common side
      effect. However, the depletion of hepatic macrophages with gadolinium chloride
      blunts hepatic fibrosis. Because endotoxin is a key activator of hepatic
      macrophages, this study was designed to test the hypothesis that LPS signaling
      through CD14 contributes to hepatic fibrosis caused by experimental cholestasis.
      Wild-type mice and CD14 knockout mice (CD14(-/-)) underwent sham operation or
      bile duct ligation and were killed 3 wk later. Measures of liver injury, such as
      focal necrosis, biliary cell proliferation, and inflammatory cell influx, were
      not significantly different among the strains 3 wk after bile duct ligation.
      Markers of liver fibrosis such as Sirius red staining, liver hydroxyproline, and
      alpha-smooth muscle actin expression were blunted in CD14(-/-) mice compared with
      wild-type mice after bile duct ligation. Despite no difference in lymphocyte
      infiltration, the macrophage/monocyte activation marker OX42 (CD11b) and the
      oxidative stress/lipid peroxidation marker 4-hydroxynonenal were significantly
      upregulated in wild-type mice after bile duct ligation but not in CD14(-/-) mice.
      Increased profibrogenic cytokine mRNA expression in the liver after bile duct
      ligation was significantly blunted in CD14(-/-) mice compared with the wild type.
      The hypothesis that LPS was involved in experimental cholestatic liver fibrosis
      was tested using mice deficient in LPS-binding protein (LBP(-/-)). LBP(-/-) mice
      had less liver injury and fibrosis (Siruis red staining and hydroxyproline
      content) compared with wild-type mice after bile duct ligation. In conclusion,
      these data demonstrate that endotoxin in a CD14-dependent manner exacerbates
      hepatic fibrogenesis and macrophage activation to produce oxidants and cytokines
      after bile duct ligation.

PMID- 16439471
TI  - Common cavity pressure during gastroesophageal reflux: reassessment using
      simultaneous pressure, impedance, and ultrasound imaging.
AB  - An increase in intraesophageal pressure during transient lower esophageal
      sphincter (LES) relaxation [referred to as common cavity (CC) pressure] is
      thought to be a marker of gastroesophageal reflux (GER). Multiluminal impedance
      (MII) measurement is a sensitive marker of reflux entry into the esophagus during
      GER. We recorded GER using esophageal pressure, pH, impedance, and intraluminal
      ultrasound (US) images to understand the genesis of the esophageal CC pressure.
      Nine normal subjects underwent simultaneous MII/pH/pressure and US image
      recording of the esophagus for 2 h following a standardized meal. MII and
      pressure transducers were located at 5 and 15 cm above the LES. The US transducer
      and pH sensors were also placed at 5 cm above the LES. Refluxate entry into the
      esophagus by MII criteria was determined relative to the onset of CC pressure
      wave. Esophageal lumen cross-sectional area (CSA) and muscle CSA during GER were
      determined from the US images. Eighty liquid GER episodes identified using MII
      criteria, of which 55 were clearly associated with CC pressure waves, were
      analyzed. The GER reached 15 cm above LES in 49 of 55 (89%) by MII criteria, but
      the CC pressure wave was observed at 5 and 15 cm during all episodes. The
      propagation of the CC pressure wave was simultaneous between 5 and 15 cm during
      49 of 55 (89%) of the GER episodes, but reflux entry by MII criteria was
      retrograde during 53 of 55 (96%) of these episodes. During 5 air-reflux episodes,
      MII showed a simultaneous reflux entry between the 5- and 15-cm site, however,
      the CC pressure preceded reflux entry during all of these episodes. There was
      poor correlation between the luminal CSA and the magnitude of CC pressure (R(2) =
      0.144). US images revealed a close temporal correlation between CC pressure and
      the increase in esophageal muscle thickness and muscle CSA (markers of
      longitudinal muscle contraction). Disassociation between CC pressure and MII
      detected reflux suggests that the onset of CC pressure is not due to GER. We
      speculate that longitudinal muscle contraction plays an important role in the
      genesis of CC pressure.

PMID- 16439472
TI  - Roles of phosphatidylinositol 3-kinase and osteopontin in steatosis and
      aminotransferase release by hepatocytes treated with methionine-choline-deficient
      medium.
AB  - Feeding mice a methionine and choline-deficient (MCD) diet serves as an
      experimental animal model for nonalcoholic steatohepatitis (NASH). In the present
      study we examined the effect of exposing AML-12 hepatocytes to MCD culture medium
      in regard to mechanisms of steatosis and alanine amino-transferase (ALT) release.
      Cells exposed to MCD medium developed significant and progressive steatosis from
      6 to 24 h and also had significantly increased loss of ALT into the medium at 18
      and 24 hours of incubation. No increased oxidative injury or cell death was
      observed. Osteopontin (OPN) mRNA in cells and protein expression in medium were
      significantly increased during 6-24 hours of incubation. MCD medium treatment
      also resulted in activation of PI3-kinase by 30 minutes and its downstream target
      p-Akt within 1hour of incubation. Steatosis was associated with increased
      expression of microsomal triglyceride transfer protein (MTTP) mRNA and increased
      ALT release with over expression of ALT mRNA, all of which were completely
      prevented by inhibition of PI3-kinase (LY294002). Blocking OPN signaling by
      treating with anti-OPN or anti-beta3-integrin antibody prevented the increased
      ALT release while only partially prevented the increased ALT mRNA expression, but
      had no effect on either steatosis or MTTP expression. In conclusion, incubation
      of cultured hepatocytes with MCD medium results in cellular steatosis and OPN
      dependent ALT release. PI3-kinase plays a central role in signaling the MCD
      medium-induced steatosis and increased OPN expression, whereas OPN appears to
      play a role in signaling hepatocyte ALT release but not steatosis.

PMID- 16439473
TI  - Involvement of Toll-like receptor 4 in acetaminophen hepatotoxicity.
AB  - The objective of this study was to determine whether Toll-like receptor 4 (TLR4)
      has a role in alcohol-mediated acetaminophen (APAP) hepatotoxicity. TLR4 is
      involved in the inflammatory response to endotoxin. Others have found that
      ethanol-mediated liver disease is decreased in C3H/HeJ mice, which have a mutated
      TLR4 resulting in a decreased response to endotoxin compared with endotoxin
      responsive mice. In the present study, short-term (1 wk) pretreatment with
      ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, caused
      no histologically observed liver damage in either C3H/HeJ mice or endotoxin
      responsive C3H/HeN mice, despite an increase in nitrotyrosine levels in the
      livers of C3H/HeN mice. In C3H/HeN mice pretreated with the alcohols, subsequent
      exposure to APAP caused a transient decrease in liver nitrotyrosine formation,
      possibly due to competitive interaction of peroxynitrite with APAP producing 3
      nitroacetaminophen. Treatment with APAP alone resulted in steatosis in addition
      to congestion and necrosis in both C3H/HeN and C3H/HeJ mice, but the effects were
      more severe in endotoxin-responsive C3H/HeN mice. In alcohol-pretreated endotoxin
      responsive C3H/HeN mice, subsequent exposure to APAP resulted in further
      increases in liver damage, including severe steatosis, associated with elevated
      plasma levels of TNF-alpha. In contrast, alcohol pretreatment of C3H/HeJ mice
      caused little to no increase in APAP hepatotoxicity and no increase in plasma TNF
      alpha. Portal blood endotoxin levels were very low and were not detectably
      elevated by any of the treatments. In conclusion, this study implicates a role of
      TLR4 in APAP-mediated hepatotoxicity.

PMID- 16439474
TI  - Coiled-coil nanomechanics and uncoiling and unfolding of the superhelix and alpha
      helices of myosin.
AB  - The nanomechanical properties of the coiled-coils of myosin are fundamentally
      important in understanding muscle assembly and contraction. Force spectra of
      single molecules of double-headed myosin, single-headed myosin, and coiled-coil
      tail fragments were acquired with an atomic force microscope and displayed
      characteristic triphasic force-distance responses to stretch: a rise phase (R)
      and a plateau phase (P) and an exponential phase (E). The R and P phases arise
      mainly from the stretching of the coiled-coils, with the hinge region being the
      main contributor to the rise phase at low force. Only the E phase was analyzable
      by the worm-like chain model of polymer elasticity. Restrained molecular
      mechanics simulations on an existing x-ray structure of scallop S2 yielded force
      spectra with either two or three phases, depending on the mode of stretch. It
      revealed that coiled-coil chains separate completely near the end of the P phase
      and the stretching of the unfolded chains gives rise to the E phase. Extensive
      conformational searching yielded a P phase force near 40 pN that agreed well with
      the experimental value. We suggest that the flexible and elastic S2 region,
      particularly the hinge region, may undergo force-induced unfolding and extend
      reversibly during actomyosin powerstroke.

PMID- 16439475
TI  - Caspase-dependent secondary lens fiber cell disintegration in alphaA-/alphaB
      crystallin double-knockout mice.
AB  - alphaB-crystallin has been demonstrated, in tissue culture experiments, to be a
      caspase 3 inhibitor; however, no animal model studies have yet been described.
      Here, we show that morphological abnormalities in lens secondary fiber cells of
      alphaA-/alphaB-crystallin gene double knockout (DKO) mice are consistent with,
      and probably result from, elevated DEVDase and VEIDase activities, corresponding
      to caspase 3 and caspase 6, respectively. Immunofluorescence microscopy revealed
      an increased amount of caspase 6, and the active form of caspase 3, in specific
      regions of the DKO lens, coincident with the site of cell disintegration. TUNEL
      labeling illustrated a higher level of DNA fragmentation in the secondary fiber
      lens cells of DKO mice, compared with wild-type mice. Using a pull-down assay, we
      show interaction between caspase 6 and alphaA- but not alphaB-crystallin. These
      studies suggest that alpha-crystallin plays a role in suppressing caspase
      activity, resulting in retention of lens fiber cell integrity following
      degradation of mitochondria and other organelles, which occurs during the
      apoptosis-like pathway of lens cell terminal differentiation.

PMID- 16439476
TI  - Slit2 and netrin 1 act synergistically as adhesive cues to generate tubular bi
      layers during ductal morphogenesis.
AB  - Development of many organs, including the mammary gland, involves ductal
      morphogenesis. Mammary ducts are bi-layered tubular structures comprising an
      outer layer of cap/myoepithelial cells (MECs) and an inner layer of luminal
      epithelial cells (LECs). Slit2 is expressed by cells in both layers, with
      secreted SLIT2 broadly distributed throughout the epithelial compartment. By
      contrast, Robo1 is expressed specifically by cap/MECs. Loss-of-function mutations
      in Slit2 and Robo1 yield similar phenotypes, characterized by disorganized end
      buds (EBs) reminiscent of those present in Ntn1(-/-) glands, suggesting that
      SLIT2 and NTN1 function in concert during mammary development. Analysis of Slit2(
      /-);Ntn1(-/-) glands demonstrates an enhanced phenotype that extends through the
      ducts and is characterized by separated cell layers and occluded lumens.
      Aggregation assays show that Slit2(-/-);Ntn1(-/-) cells, in contrast to wild-type
      cells, do not form bi-layered organoids, a defect rescued by addition of SLIT2.
      NTN1 has no effect alone, but synergistically enhances this rescue. Thus, our
      data establish a novel role for SLIT2 as an adhesive cue, acting in parallel with
      NTN1 to generate cell boundaries along ducts during bi-layered tube formation.

PMID- 16439477
TI  - Netrin 1 regulates ventral tangential migration of guidepost neurons in the
      lateral olfactory tract.
AB  - In the developing nervous system, functional neural networks are constructed with
      intricate coordination of neuronal migrations and axonal projections. We have
      previously reported a ventral tangential migration of a special type of cortical
      neurons, lot cells, in the mouse embryo. These neurons originate from the
      ventricular zone of the entire neocortex, tangentially migrate in the surface
      layer of the neocortex into the ventral direction, align in the future pathway of
      the lateral olfactory tract (LOT) and eventually guide the projection of LOT
      axons. In this study, we developed an organotypic culture system to investigate
      the regulation of this cell migration in the developing telencephalon. Our data
      show that the neocortex contains the signals that direct lot cells ventrally,
      that the ganglionic eminence excludes lot cells by repelling the migration and
      that lot cells are attracted to netrin 1, an axon guidance factor. Furthermore,
      we demonstrate that mutations in the genes encoding netrin 1 and its functional
      receptor Dcc lead to inappropriate distribution of lot cells and subsequent
      partial disruption of LOT projection. These results suggest that netrin 1
      regulates the migration of lot cells and LOT projections, possibly by ensuring
      the correct distribution of these guidepost neurons.

PMID- 16439478
TI  - The highly ordered assembly of retinal axons and their synaptic partners is
      regulated by Hedgehog/Single-minded in the Drosophila visual system.
AB  - During development of the Drosophila visual center, photoreceptor cells extend
      their axons (R axons) to the lamina ganglion layer, and trigger proliferation and
      differentiation of synaptic partners (lamina neurons) by delivering the inductive
      signal Hedgehog (Hh). This inductive mechanism helps to establish an orderly
      arrangement of connections between the R axons and lamina neurons, termed a
      retinotopic map because it results in positioning the lamina neurons in close
      vicinity to the corresponding R axons. We found that the bHLH-PAS transcription
      factor Single-minded (Sim) is induced by Hh in the lamina neurons and is required
      for the association of lamina neurons with R axons. In sim mutant brains, lamina
      neurons undergo the first step of differentiation but fail to associate with R
      axons. As a result, lamina neurons are set aside from R axons. The data reveal a
      novel mechanism for regulation of the interaction between axons and neuronal cell
      bodies that establishes precise neuronal networks.

PMID- 16439479
TI  - Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt
      signaling and promoting extracellular matrix production.
AB  - Development of the vertebrate gut is controlled by paracrine crosstalk between
      the endodermal epithelium and the associated splanchnic mesoderm. In the adult,
      the same types of signals control epithelial proliferation and survival, which
      account for the importance of the stroma in colon carcinoma progression. Here, we
      show that targeting murine Foxf1 and Foxf2, encoding forkhead transcription
      factors, has pleiotropic effects on intestinal paracrine signaling. Inactivation
      of both Foxf2 alleles, or one allele each of Foxf1 and Foxf2, cause a range of
      defects, including megacolon, colorectal muscle hypoplasia and agangliosis. Foxf
      expression in the splanchnic mesoderm is activated by Indian and sonic hedgehog
      secreted by the epithelium. In Foxf mutants, mesenchymal expression of Bmp4 is
      reduced, whereas Wnt5a expression is increased. Activation of the canonical Wnt
      pathway -- with nuclear localization of beta-catenin in epithelial cells -- is
      associated with over-proliferation and resistance to apoptosis. Extracellular
      matrix, particularly collagens, is severely reduced in Foxf mutant intestine,
      which causes epithelial depolarization and tissue disintegration. Thus, Foxf
      proteins are mesenchymal factors that control epithelial proliferation and
      survival, and link hedgehog to Bmp and Wnt signaling.

PMID- 16439480
TI  - Crossveinless 2 is an essential positive feedback regulator of Bmp signaling
      during zebrafish gastrulation.
AB  - Signaling by bone morphogenetic proteins (Bmps) plays a pivotal role in
      developmental and pathological processes, and is regulated by a complex interplay
      with secreted Bmp binding factors, including Crossveinless 2 (Cvl2). Although
      structurally related to the Bmp antagonist Chordin, Crossveinless 2 has been
      described to be both a Bmp agonist and antagonist. Here, we present the first
      loss-of-function study of a vertebrate cvl2 homologue, showing that zebrafish
      cvl2 is required in a positive feedback loop to promote Bmp signaling during
      embryonic dorsoventral patterning. In vivo, Cvl2 protein undergoes proteolytic
      cleavage and this cleavage converts Cvl2 from an anti- to a pro-Bmp factor.
      Embryonic epistasis analyses and protein interaction assays indicate that the pro
      Bmp function of Cvl2 is partly accomplished by competing with Chordin for binding
      to Bmps. Studies in cell culture and embryos further suggest that the anti-Bmp
      effect of uncleaved Cvl2 is due to its association with the extracellular matrix,
      which is not found for cleaved Cvl2. Our data identify Cvl2 as an essential pro
      Bmp factor during zebrafish embryogenesis, emphasizing the functional diversity
      of Bmp binding CR-domain proteins. Differential proteolytic processing as a mode
      of regulation might account for anti-Bmp effects in other contexts.

PMID- 16439481
TI  - Monocyte chemotactic protein-1 in the follicle of the menstrual and IVF cycle.
AB  - Ovulation constitutes an inflammatory-like process, with macrophages migrating
      into the follicle. This study evaluates the production of two macrophage-specific
      chemokines, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory
      protein-1alpha (MIP-1alpha), in the human follicle at ovulation. Blood samples,
      follicular fluids and follicular cells were collected during menstrual and IVF
      cycles. Levels of MCP-1 and MIP-1alpha were measured in follicular fluid, blood
      plasma and cultured media (granulosa, theca and granulosa-lutein cells [GLCs]).
      Cells were cultured with or without LH, FSH, interleukin (IL)-1alpha, IL-1beta,
      tumour necrosis factor (TNF) alpha, progesterone or estradiol. The levels of MCP
      1 were markedly higher in follicular fluid as compared with blood plasma in both
      menstrual and IVF cycles. The difference in MCP-1 levels between follicular fluid
      and plasma in menstrual cycles increased from the follicular phase (three-fold
      difference) to the late ovulatory phase (25-fold). Levels of MIP-1alpha were low
      in plasma and follicular fluid of both menstrual and IVF cycles. Theca cells from
      follicles of menstrual cycles secreted both MCP-1 and MIP-1alpha under basal
      conditions, and the secretion was increased by addition of IL-1beta (MCP-1 and
      MIP-1alpha) and IL-1alpha (MCP-1). GLCs secreted MCP-1 under basal conditions and
      also MIP-1alpha after IL-1beta stimulation. The macrophage-specific chemokine MCP
      1 is highly expressed and is induced by IL-1 in the theca layer of the human
      follicle at ovulation.

PMID- 16439482
TI  - Multiple events on single molecules: unbiased estimation in single-molecule
      biophysics.
AB  - Most analyses of single-molecule experiments consist of binning experimental
      outcomes into a histogram and finding the parameters that optimize the fit of
      this histogram to a given data model. Here we show that such an approach can
      introduce biases in the estimation of the parameters, thus great care must be
      taken in the estimation of model parameters from the experimental data. The bias
      can be particularly large when the observations themselves are not statistically
      independent and are subjected to global constraints, as, for example, when the
      iterated steps of a motor protein acting on a single molecule must not exceed the
      total molecule length. We have developed a maximum-likelihood analysis,
      respecting the experimental constraints, which allows for a robust and unbiased
      estimation of the parameters, even when the bias well exceeds 100%. We
      demonstrate the potential of the method for a number of single-molecule
      experiments, focusing on the removal of DNA supercoils by topoisomerase IB, and
      validate the method by numerical simulation of the experiment.

PMID- 16439483
TI  - C/EBPbeta is a critical mediator of steroid hormone-regulated cell proliferation
      and differentiation in the uterine epithelium and stroma.
AB  - During early pregnancy, steroid hormones estrogen (E) and progesterone (P)
      regulate a complex series of interactions between the implanting embryo and the
      uterus by controlling the proliferation and differentiation of uterine epithelium
      and stroma in a timely manner. To identify the steroid-regulated genes that
      control these functions, we performed messenger RNA profiling of mouse uterine
      tissues at the time of implantation. Our analysis revealed that the expression of
      the transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) is
      rapidly induced in the pregnant uterus at the time of blastocyst attachment. The
      expression of C/EBPbeta increased further during the decidualization phase of
      pregnancy and was localized in the proliferating as well as the decidualized
      stromal cells surrounding the implanted embryo. Administration of E or P to
      ovariectomized females induced C/EBPbeta expression in both uterine epithelium
      and stroma, showing a dual regulation of this gene by these hormones. The female
      C/EBPbeta-null mice are infertile. We, therefore, assessed steroid-hormone
      dependent responses in the uteri of these mice. We observed that E-induced
      proliferation of uterine epithelial cells is markedly compromised in the absence
      of C/EBPbeta. Most strikingly, there was a complete lack of response of the
      C/EBPbeta-deficient uteri to an artificial deciduogenic stimulus, indicating a
      critical role of this transcription factor in regulating the decidualization
      program. Further analysis revealed defects in steroid-induced stromal cell
      proliferation and differentiation in C/EBPbeta-null uteri. Collectively, our
      studies established that C/EBPbeta is a key mediator of steroid responsiveness of
      the epithelium and stroma in the mouse uterus.

PMID- 16439485
TI  - Dispelling myths and removing barriers about insulin in type 2 diabetes.

PMID- 16439486
TI  - Systematically initiating insulin: the staged diabetes management approach.

PMID- 16439487
TI  - Pediatric pumps: barriers and breakthroughs.

PMID- 16439490
TI  - Treating the spectrum of type 2 diabetes: emphasis on insulin pump therapy.

PMID- 16439491
TI  - Future developments in insulin pump therapy: progression from continuous
      subcutaneous insulin infusion to a sensor-pump system.

PMID- 16439492
TI  - Assessing psychosocial variables: a tool for diabetes educators.
AB  - The purpose of this article is to share an educational strategy or tool that is
      relevant for use in patient and professional diabetes education. The tool offers
      an opportunity for diabetes educators to screen for psychosocial variables such
      as depression or emotional distress. A systematic review of the literature was
      conducted to identify psychological variables that have an impact on individuals
      living with diabetes and their ability to self-manage their disease. The
      literature revealed that both depression and emotional distress related to
      diabetes was experienced by individuals with diabetes along with those
      individuals who were unable to self-management their disease. The Accu-Check
      Interview is a computer software program that may assist diabetes educators to
      provide diabetes education. Use of the Accu-Check Interview software program has
      been implemented at various sites including the Joslin Clinic (Boston, Mass),
      Baystate Medical Center (Springfield, Mass), and Emerson Hospital (Concord,
      Mass). The Diabetes Self Care Profile is a Web-based version of the Accu-Check
      Interview and can be accessed as a demonstration in English and Spanish. These
      tools allow diabetes educators to screen for psychosocial variables and address
      issues with individuals while using a motivational interviewing approach.

PMID- 16439495
TI  - Self-monitoring of physical activity: effects on self-efficacy and behavior in
      people with type 2 diabetes.
AB  - PURPOSE: The purpose of this study was to test the effect of keeping daily
      activity records on physical activity levels and self-efficacy for physical
      activity in adults with type 2 diabetes, and to examine the feasibility and
      acceptability of this intervention from the perspective of the participants.
      METHODS: This intervention study included 58 individuals with type 2 diabetes
      aged 40 to 65 years. Participants were randomly assigned: individuals in the
      intervention group kept daily activity records for 6 weeks, mailed to the
      researcher every 2 weeks. Data collection was completed at the beginning of the
      study and 6 weeks later, using the habitual physical activity index and the self
      efficacy for exercise scale. Participants in the intervention group also
      completed the perceived feasibility checklist. RESULTS: The intervention resulted
      in enhanced self-efficacy. Physical activity improved in both the intervention
      and control groups. Activity recording was judged to be acceptable and feasible.
      CONCLUSIONS: Daily activity recording can be used as part of a program to
      increase physical activity self-efficacy levels. Focused interactions between
      health care providers and patients may be enough to motivate people to higher
      levels of physical activity. The relationship between self-efficacy and behavior
      is complex and should be the subject of further research.

PMID- 16439496
TI  - Low-glycemic index carbohydrates: an effective behavioral change for glycemic
      control and weight management in patients with type 1 and 2 diabetes.
AB  - PURPOSE: This retrospective study evaluated the incorporation of low-glycemic
      index (GI) carbohydrates into daily meal planning as an effective behavioral
      lifestyle change to improve glycemic control and weight management in patients
      with type 1 and 2 diabetes. METHODS: Twenty-one subjects participated in this
      study. All office visits and interview sessions took place in a 2-physician
      private medical practice setting in Wayne, New Jersey. Patients' pre- and
      postcounseling HbA1c and body mass index (BMI) values and their antidiabetic
      medication dosages were recorded. Audiotaped interviews were conducted using the
      10-question Glycemic Index Foods Quiz (GIFQ) and the 29-question Interview
      Questionnaire (IQ). The GI values of pre- and postcounseling meals were
      calculated. Assessment was based on triangulating the subjects' adherence to the
      low-GI carbohydrate behavioral change and the primary outcome measures: HbA1c and
      BMI. RESULTS: Low-GI medical nutrition therapy (LGI-MNT) counseling reduced HbA1c
      by 19% (mean drop of 1.5 U) and decreased BMI by 8% (mean loss of 17 pounds).
      This was accomplished by the participants independently lowering the GI values of
      their meals by 25% (mean reduction of 15 points). Results were achieved over a
      time frame of 3 to 36 months from the initial LGI-MNT counseling session.
      CONCLUSIONS: Daily incorporation of low-GI carbohydrates in meal planning can be
      an effective diabetes self-management strategy for glycemic control and weight
      management. The documented responses to the subjects' conceptual and practical
      knowledge of the GI confirm their acceptance of this approach as a permanent
      behavioral lifestyle change and not a "diet." The positive results of this study
      attest to what worked for these subjects, inviting diabetes educators to consider
      offering low-GI dietary advice to their diabetes patients.

PMID- 16439497
TI  - Using focus groups to develop a culturally competent diabetes self-management
      program for Mexican Americans.
AB  - PURPOSE: The purpose of this study was to describe factors that facilitate or
      hinder diabetes self-management and elicit participants' preferences and
      recommendations about the essential components of a culturally competent diabetes
      self-management program. METHODS: Latino patients with type 2 diabetes and their
      family caregivers were interviewed in focus groups. Four focus groups consisted
      of patients, and 2 groups consisted of family caregivers for a total of 40
      participants. Participants were assigned to groups based on break characteristics
      of gender and preferred language. RESULTS: "Being in the dark" emerged as an
      important concern, and patient respondents wanted timely access to information
      that they deemed understandable about how to manage their diabetes. Family
      members' support and understanding were crucial in maintaining lifestyle changes.
      Patient and family caregiver participants wanted a self-management program to
      incorporate information on how to modify traditional foods, home remedies, and
      stress management. Preferences for information delivery included group didactic
      and interactive sessions, written information, and videotapes. Higher technology
      strategies using computers were not seen as useful. CONCLUSIONS: Culturally
      competent diabetes self-management for Latinos should incorporate the family and
      include techniques for stress management as well as diet modification.
      Information delivery should include a variety of techniques.

PMID- 16439498
TI  - Impact of using a pedometer on time spent walking in older adults with type 2
      diabetes.
AB  - PURPOSE: The purpose of this study was to investigate the impact of using a
      pedometer on time spent walking, in sedentary and overweight adults with type 2
      diabetes participating in a coaching intervention. It was hypothesized that
      participants using a pedometer would spend more time walking than would
      nonpedometer participants. Method A sample of 57 men and women with a mean age of
      62 years participated in a randomized controlled trial in a community setting.
      Participants were allocated to either a pedometer and coaching (intervention)
      group or a coaching-only (control) group. Coaching for both groups involved
      education, goal setting, and supportive/motivational strategies to increase time
      spent walking. The duration of the study was 6 months, with blood pressure,
      glycosylated hemoglobin, anthropometric, and fitness measurements assessed at
      baseline and at 3-month intervals. RESULTS: A repeated-measures analysis of
      variance indicated that the coaching-only group spent significantly more time
      walking than did the pedometer group. However, when an analysis of covariance
      with all the other variables as covariates was performed, group membership had no
      influence on time spent walking. Significant reductions in waist circumference
      and weight were achieved for both groups from baseline to 6 months.
      Cardiovascular fitness also increased significantly for both groups. CONCLUSION:
      The study demonstrated that previously sedentary older adults with type 2
      diabetes, supported with a coaching intervention, were able to achieve the
      physical activity targets known to be beneficial to health. However, using a
      pedometer added no further benefit. Further research on the impact of specific
      coaching strategies in diabetes management is warranted.

PMID- 16439499
TI  - Diabetes nurse educators and preconception counseling.
AB  - PURPOSE: The purpose of this study was to examine the diabetes nurse educator's
      role, practice, and training in preconception counseling (PC) when caring for
      adolescents with diabetes. METHODS: A descriptive, correlational research design,
      using a cross-sectional survey technique, was used. Subjects were 2003 registered
      nurse members of the American Association of Diabetes Educators. A survey
      instrument was developed by the investigator and placed on the World Wide Web.
      RESULTS: Although most of the diabetes nurse educators were aware of PC, most
      reported not having received any training in PC and would benefit from this
      education. Thirty percent of the respondents did not routinely provide PC to
      their adult female clients, and 40% did not provide this to adolescents.
      CONCLUSIONS: Results of this study suggest that the diabetes nurse educators in
      this sample would benefit from receiving instruction about PC. The diabetes nurse
      educators should be trained to provide PC to all female clients with diabetes of
      childbearing age starting at puberty.

PMID- 16439501
TI  - Dynamics of FSH-induced follicular growth in subfertile women: relationship with
      age, insulin resistance, oocyte yield and anti-Mullerian hormone.
AB  - BACKGROUND: During excess FSH treatment, different categories of follicles can be
      discerned: those responding and appearing to grow immediately (FolsS8) and those
      appearing subsequently during the follicular phase (Fols/d). These follicular
      categories were explored in cycles of assisted reproduction in the context of
      follicular biology, including primordial follicle pool (PFP) depletion, age,
      insulin resistance and potential markers. METHODS: Follicular cohorts were
      examined in 365 conventional ART cycles and related to patient insulin
      sensitivity, plasma FSH and anti-Mullerian hormone (AMH). RESULTS: Age had no
      influence upon the FolsS8 category but was associated with a significant (P <
      0.005) decline in the Fols/d. In contrast, insulin-resistant polycystic ovary
      syndrome (IR-PCOS) showed a significant (P = 0.005) increase in FolsS8.
      Circulating AMH correlated strongly with oocyte yield and Fols/d. CONCLUSION: Age
      showed little impact on the initial follicular cohort, but a significant impact
      upon the secondary cohort, while insulin resistance appeared to promote the
      former category alone. The disturbance to follicular dynamics and AMH in IR-PCOS
      reflected a larger stockpile of FSH-sensitive follicles. Circulating AMH appears
      to represent all categories of antral follicles observed.

PMID- 16439502
TI  - Ovulation detection methods for urinary hormones: precision, daily and
      intermittent sampling and a combined hierarchical method.
AB  - BACKGROUND: We evaluate the performance of ovulation detection methods and
      present new approaches, including evaluation of methods for precision, combining
      multiple markers into a hierarchical system and using ovulation markers in
      intermittent sampling designs. METHODS: With serum LH peak day as the 'gold
      standard' of ovulation, we estimated accuracy and precision of ovulation day
      algorithms using 30 ovulatory menstrual cycles with daily urinary and serum
      hormones and transvaginal ultrasound. Sensitivity and specificity for estimating
      the presence of ovulation were tested using visually assessed ovulatory (30) and
      anovulatory (22) cycles. RESULTS: Sensitivity and specificity ranged from 70 to
      100% for estimating presence of ovulation with twice-per-cycle, weekly, twice
      weekly, every-other-day and daily specimens. A combined hierarchical method
      estimated ovulation day using daily specimens within +/-2 days of the gold
      standard in 93% of cases. Accuracy of estimating ovulation day within +/-2 days
      using intermittent sampling ranged from 40% (weekly sampling) to 97% (every-other
      day). CONCLUSIONS: A combined hierarchical algorithm using precise and accurate
      markers allows maximal use of available data for efficient and objective
      identification of ovulation using daily specimens. In intermittent sampling
      designs, the presence and the timing of ovulation can be estimated with good
      sensitivity, specificity and accuracy.

PMID- 16439503
TI  - Ovarian response to stimulation of HIV-positive patients during IVF treatment: a
      matched, controlled study.
AB  - BACKGROUND: Our aim was to compare the ovarian response of HIV-positive and 
      negative patients during IVF. METHODS: Setting - HIV and IVF reference university
      hospital. Twenty-seven HIV-infected patients who had undergone IVF between March
      2000 and March 2005 were matched with 77 HIV-negative patients for age, aetiology
      of infertility, whether it was primary or secondary infertility, duration of
      infertility, history of pelvic surgery and type of pituitary inhibition. Outcome 
      poor responders were defined using one of the following criteria: a cancelled
      cycle (for insufficient ovarian response), less than four mature follicles (> or
      = 16 mm), peak serum levels of E2 lower than 1000 pg/ml. RESULTS: There were no
      differences between the two groups of patients for the matched criteria. The
      proportion of African women and of women with a history of pelvic inflammatory
      disease was significantly higher among HIV patients than among the control group.
      With the exception of a lower number of transferred embryos among HIV-positive
      patients versus HIV-negative ones (1.3 versus 1.9; P = 0.035), there was no
      significant difference between the two groups of patients regarding ovarian
      response parameters. CONCLUSION: HIV-infected patients who are in good general
      condition and who are matched to a control group present a similar ovarian
      response to stimulation, suggesting the existence of a similar ovarian reserve.

PMID- 16439504
TI  - Quality of life after laparoscopic colorectal resection for endometriosis.
AB  - BACKGROUND: Indications of colorectal resection for endometriosis remain
      controversial because of the risk of major complications. Therefore, the aims of
      the current study were to evaluate the efficacy of laparoscopic segmental
      colorectal resection for endometriosis on quality of life and gynaecologic and
      digestive symptoms, and its complications. METHODS: After magnetic resonance
      imaging and rectal endoscopic sonographic evaluation of symptomatic colorectal
      endometriosis, 58 consecutive women requiring colorectal resection were included
      in this study. Symptom questionnaires and the short-form (SF)-36 Health Status
      and the quality of life score were completed. Linear intensity scores for several
      gynaecologic and digestive symptoms and perioperative complications were also
      recorded. RESULTS: Fifty-one women (88%) underwent laparoscopic segmental
      colorectal resection and seven required laparoconversion. Major complications
      occurred in nine cases (15.5%), including six rectovaginal fistulae (10.3%), and
      the three remaining complications corresponded to a haemoperitoneum, a
      uroperitoneum and a pelvic abscess. Median follow-up after colorectal resection
      was 22.5 months (2-55 months). A significant improvement in dysmenorrhoea (P <
      0.0001), dysparaeunia (P < 0.0001), bowel movement pain or cramping (P < 0.0001),
      pain on defecation (P < 0.0001), diarrhoea (P < 0.016), lower back pain (P <
      0.0001) and asthaenia (P < 0.0002) was observed. Tenesmus, rectorrhagia and
      constipation were not improved. All the items of the SF-36 Health Status and the
      quality of life score were improved after colorectal resection for endometriosis.
      CONCLUSION: Laparoscopic segmental colorectal resection for endometriosis
      significantly improves quality of life and gynaecologic and digestive symptoms.
      However, women have to be informed on the risk of complications including
      rectovaginal fistula.

PMID- 16439505
TI  - Reduction of postoperative adhesions with an auto-crosslinked hyaluronan gel in
      gynaecological laparoscopic surgery: a blinded, controlled, randomized,
      multicentre study.
AB  - BACKGROUND: Following myomectomy, postoperative adhesions occur in many patients
      with adverse effects on fertility. This study investigated the applicability,
      safety and efficacy of an auto-crosslinked hyaluronan gel in preventing adhesion
      formation after laparoscopic myomectomy. METHODS: Fifty-two patients aged 22-42
      years, undergoing surgery at four centres, were randomly allocated to receive
      either the gel or no adhesion prevention. The incidence and severity of
      postoperative adhesions were assessed laparoscopically after 12-14 weeks in a
      blinded, scored fashion. The primary efficacy variable was the presence/absence
      of postoperative adhesions at second-look. RESULTS: A nonsignificantly higher
      proportion of patients receiving the gel were free from adhesions (13 of 21; 62%)
      compared with control patients (9 of 22; 41%), with a statistically significant
      difference between the severity of uterine adhesions at baseline and at second
      look (0.3 +/- 0.9 versus 0.8 +/- 1.0, P < 0.05). In subjects undergoing
      myomectomy without concomitant surgery, the proportion of adhesion-free patients
      was 8 of 12 (67%) and 4 of 11 (36%) (not significant) in the gel and control
      groups, respectively, with a significant difference in the mean severity scores
      (P < 0.05). In subjects without uterine adhesions before myomectomy, 12 of 18
      (67%) and 8 of 20 (40%) patients in the gel and control groups, respectively were
      adhesion-free (not significant), with a significant difference in the severity of
      uterine adhesions (P = 0.05). CONCLUSIONS: Our results suggest that the auto
      crosslinked hyaluronan gel may have a favourable safety profile and efficacious
      antiadhesive action following laparoscopic myomectomy.

PMID- 16439506
TI  - Meiotic segregation of rare Robertsonian translocations: sperm analysis of three
      t(14q;22q) cases.
AB  - BACKGROUND: The t(14;22) remains one of the rare Robertsonian translocations
      observed in human, with an occurrence estimated at 1.2%. Three cases of rare
      Robertsonian translocation t(14;22) were investigated for meiotic segregation in
      sperm samples from male carriers using the fluorescent in situ hybridization
      (FISH) procedure. The three carriers included two men with an abnormal semen
      analysis and one with normal semen parameters. METHODS: Both locus-specific
      probes and whole-chromosome painting probes, specific for chromosomes 14 and 22,
      were used in this study. The number of spermatozoa scored for each probe set
      ranged from 3279 to 10,024. RESULTS: In the three carriers, similar frequencies,
      ranging from 78.53 to 81.76%, were found for normal and balanced spermatozoa
      resulting from alternate segregation. The total proportion of unbalanced
      spermatozoa resulting from adjacent modes of segregation ranged from 17.59 to
      20.94%. CONCLUSION: This finding confirmed the predominance of alternate
      segregation over other segregation types in all Robertsonian translocations and
      indicates a higher production of imbalances in the t(14;22) than in most of the
      Robertsonian translocations previously analysed. This could be related to the
      variable location of breakpoints in Robertsonian translocations. This breakpoint
      diversity could also play a role in the differences in reproductive status
      observed in male carriers of Robertsonian translocations.

PMID- 16439508
TI  - Gender-specific association of the factor V Leiden mutation with fertility and
      fecundity in a historic cohort. The Leiden 85-Plus Study.
AB  - BACKGROUND: Factor V Leiden (FVL, Arg506Gln) mutation may facilitate embryo
      implantation and increase fertility and fecundity. This was studied in subjects
      who were of childbearing age in a time with minimal fertility control without
      modern contraceptive methods. METHODS: From 1986 to 1999, 1502 inhabitants of
      Leiden, The Netherlands, reaching the age of 85 years were enrolled in the Leiden
      85-Plus Study. Of 1176 subjects the FVL status was analysed, in 365 male and 811
      female subjects. RESULTS: The FVL carrier rate was 4.3%. Fertility was not
      affected by FVL status. In male subjects, fecundity (interval between marriage
      and birth of first child) was significantly increased in FVL carriers; 67% of
      male FVL carriers had a child within 371 days of marriage (therefore conceived
      within 3 months of marriage), compared with 19% of male non-carriers [relative
      risk (RR), 3.5; 95% confidence interval (CI), 2.1-5.7; P < 0.001]. Within 6
      months of marriage, 75% of male FVL carriers had conceived a child compared with
      34% male non-carriers (RR, 2.2; 95% CI, 1.5-3.2; P = 0.01). In female subjects,
      fecundity was not influenced by FVL status. CONCLUSION: Fecundity is increased in
      male FVL carriers; in female subjects, no such association was observed.

PMID- 16439507
TI  - Serum inhibin A, VEGF and TNFalpha levels after triggering oocyte maturation with
      GnRH agonist compared with HCG in women with polycystic ovaries undergoing IVF
      treatment: a prospective randomized trial.
AB  - BACKGROUND: We aimed to examine the serum levels of inhibin A, vascular
      endothelial growth factor (VEGF), tumour necrosis factor alpha (TNFalpha),
      estradiol (E2) and progesterone levels after triggering of final oocyte
      maturation with GnRH agonist compared with HCG in patients with polycystic
      ovaries (PCO) and to investigate the relationship between these markers and
      ovarian hyperstimulation syndrome (OHSS). METHODS: Twenty-eight patients with
      PCO, undergoing controlled ovarian hyperstimulation with FSH and GnRH antagonist
      for IVF-embryo transfer treatment, were randomized for triggering of final oocyte
      maturation with GnRH agonist (GnRH agonist group, n = 15) or HCG (HCG group, n =
      13). Blood samples were obtained on the day of randomization and thereafter every
      2-7 days. Serum levels of inhibin A, VEGF, TNFalpha, E2 and progesterone, the
      incidence of OHSS, ovarian size and pelvic fluid accumulation were evaluated.
      RESULTS: Serum inhibin A, E2 and progesterone levels were significantly lower in
      the GnRH agonist group compared with the HCG group, particularly on the day of
      embryo transfer (P < 0.0001). Serum VEGF and TNFalpha levels were similar between
      the two groups. Four patients in the HCG group developed severe OHSS, whereas no
      patient had any symptoms or signs of OHSS in the GnRH-agonist group (P < 0.05).
      CONCLUSIONS: In patients with PCO treated with FSH/GnRH antagonist, final oocyte
      maturation with GnRH agonist instead of HCG reduces significantly inhibin A, E2
      and progesterone levels during the luteal phase. This phenomenon reflects the
      inhibition of the corpus luteum function and may explain, at least in part, the
      mechanism of OHSS prevention in high-risk patients. Our results do not support a
      crucial role for VEGF or TNFalpha in OHSS.

PMID- 16439509
TI  - An intravital microscopy method permitting continuous long-term observations of
      ovulation in vivo in the rabbit.
AB  - BACKGROUND: A method for intravital microscopy of the rabbit ovary was developed
      to enable observations of real-time changes during ovulation in vivo. The aim was
      to correlate these events to biochemical events at specific stages of ovulation.
      METHODS: Virgin, female rabbits were primed with equine chorionic gonadotrophin
      (CG) (30-100 IU) then HCG (100 IU) 2 days later to induce ovulation. During
      anaesthesia, the right ovary was surgically exteriorized and submerged in an
      organ chamber with a microscopy lens positioned close to the ovary. Continuous
      video recordings were performed. RESULTS: Initial equine CG priming experiments
      revealed the highest ovulation rate, without premature luteinization, after 30 IU
      equine CG. This priming protocol subsequently demonstrated follicular ruptures
      11.5-14 h after HCG. Numbers of ovulations from the exteriorized and
      contralateral non-exteriorized ovary were similar. The sequence of typical
      features of ovulation was: shutdown of microcirculation in the follicular apex,
      formation of petechiae in the follicular wall and a cone-shaped structure over
      the future rupture site, marked bleeding in connection with follicular rupture
      and a fairly steady extrusion velocity of granulosa cells and the oocyte.
      CONCLUSION: This method captured a sequence of structural changes during
      ovulation. It could be combined with blood and follicular fluid sampling for
      biochemical analysis and could be used in studies on biochemical reactions in
      relation to specific changes in the follicular structure during ovulation.

PMID- 16439510
TI  - Temporal response of desmin and dystrophin proteins to progressive resistance
      exercise in human skeletal muscle.
AB  - We have investigated the adaptations of the cytoskeletal proteins desmin and
      dystrophin in relationship to known muscular adaptations of resistance exercise.
      We measured desmin, dystrophin, and actin protein contents, myosin heavy chain
      (MHC) isoform distribution, muscle strength, and muscle cross-sectional area
      (CSA) during 8 wk of progressive resistance training or after a single bout of
      unaccustomed resistance exercise. Muscle biopsies were taken from the vastus
      lateralis of 12 untrained men. For the single-bout group (n=6) biopsies were
      taken 1 wk before the single bout of exercise (week 0) and 1, 2, 4, and 8 wk
      after this single bout of exercise. For the training group (n=6), biopsies were
      taken 1 wk before the beginning of the program (week 0) and at weeks 1, 2, 4, and
      8 of the progressive resistance training program. Desmin, dystrophin, and actin
      protein levels were determined with immunoblotting, and MHC isoform distribution
      was determined using SDS-PAGE at each time point for each group. In the training
      group, desmin was significantly increased compared with week 0 beginning at week
      4 (182% of week 0; P<0.0001) and remained elevated through week 8 (172% of week
      0; P<0.0001). Desmin did not change at any time point for the single-bout group.
      Actin and dystrophin protein contents were not changed in either group at any
      time point. The percentage of MHC type IIa increased and MHC type IIx decreased
      at week 8 in the training group with no changes occurring in the single-bout
      group. Strength was significantly increased by week 2 (knee extension) and week 4
      (leg press), and it further increased at week 8 for both these exercises in the
      training group only. Muscle CSA was significantly increased at week 4 for type II
      fibers in the training group only (5,719+/-382 and 6,582+/-640 microm2, weeks 0
      and 4, respectively; P<0.05). Finally, a significant negative correlation was
      observed between the desmin-to-actin ratio and the percentage of MHC IIx (R=
      0.31; P<0.05, all time points from both groups). These data demonstrate a time
      course for muscular adaptation to resistance training in which desmin increases
      shortly after strength gains and in conjunction with hypertrophy, but before
      changes in MHC isoforms, whereas dystrophin remains unchanged.

PMID- 16439511
TI  - Effects of postural changes and removal of vestibular inputs on blood flow to the
      head of conscious felines.
AB  - Prior studies have shown that removal of vestibular inputs produces lability in
      blood pressure during orthostatic challenges (Holmes MJ, Cotter LA, Arendt HE,
      Cass SP, and Yates BJ. Brain Res 938: 62-72, 2002; Jian BJ, Cotter LA, Emanuel
      BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999). Furthermore,
      these studies led to the prediction that the blood pressure instability results
      in susceptibility for orthostatic intolerance. The present experiments tested
      this hypothesis by recording common carotid blood flow (CCBF) in conscious cats
      during head-up tilts of 20, 40, and 60 degrees amplitudes, before and after the
      surgical elimination of labyrinthine inputs through a bilateral vestibular
      neurectomy. Before vestibular lesions in most animals, CCBF remained stable
      during head-up rotations. Unexpectedly, in five of six animals, the vestibular
      neurectomy resulted in a significant increase in baseline CCBF, particularly when
      the laboratory was illuminated; on average, basal blood flow measured when the
      animals were in the prone position was 41 +/- 17 (SE) % higher after the first
      week after the lesions. As a result, even when posturally related lability in
      CCBF occurred after removal of vestibular inputs, blood supply to the head was
      not lower than when labyrinthine inputs were present. These data suggest that
      vestibular influences on cardiovascular regulation are more complex than
      previously appreciated, because labyrinthine signals appear to participate in
      setting basal rates of blood flow to the head in addition to triggering dynamic
      changes in the circulation to compensate for orthostatic challenges.

PMID- 16439512
TI  - Effect of voluntary wheel running on circadian corticosterone release and on HPA
      axis responsiveness to restraint stress in Sprague-Dawley rats.
AB  - Adaptations of the hypothalamic-pituitary-adrenal (HPA) axis to voluntary
      exercise in rodents are not clear, because most investigations use forced
      exercise protocols, which are associated with psychological stress. In the
      present study, we examined the effects of voluntary wheel running on the
      circadian corticosterone (Cort) rhythm as well as HPA axis responsiveness to, and
      recovery from, restraint stress. Male Sprague-Dawley rats were divided into
      exercise (E) and sedentary (S) groups, with E rats having 24-h access to running
      wheels for 5 wk. Circadian plasma Cort levels were measured at the end of each
      week, except for week 5 when rats were exposed to 20 min of restraint stress,
      followed by 95 min of recovery. Measurements of glucocorticoid receptor content
      in the hippocampus and anterior pituitary were performed using Western blotting
      at the termination of the restraint protocol. In week 1, circadian Cort levels
      were twofold higher in E compared with S animals, but the levels progressively
      decreased in the E group throughout the training protocol to reach similar values
      observed in S by week 4. During restraint stress and recovery, Cort values were
      similar between E and S, as was glucocorticoid receptor content in the
      hippocampus and pituitary gland after death. Compared with E, S animals had
      higher plasma ACTH levels during restraint. Taken together, these data indicate
      that 5 wk of wheel running are associated with normal circadian Cort activity and
      normal negative-feedback inhibition of the HPA axis, as well as with increased
      adrenal sensitivity to ACTH after restraint stress.

PMID- 16439513
TI  - Viral expression of insulin-like growth factor-I isoforms promotes different
      responses in skeletal muscle.
AB  - Insulin-like growth factor I (IGF-I) is a critical protein for skeletal muscle
      development and regeneration. Its ability to promote skeletal muscle hypertrophy
      has been demonstrated by several methods. Alternative splicing of the Igf-1 gene
      does not affect the mature IGF-I protein but does produce different E peptide
      extensions, which have been reported to modify the potency of IGF-I. Viral
      mediated delivery of murine IGF-IA and IGF-IB into skeletal muscle of 2-wk-old
      and 6-mo-old mice was utilized to compare the effects of the isoforms on muscle
      mass. In young mice, tissue content of IGF-I protein was significantly higher in
      rAAV-treated muscles than control muscles at 1, 2, and 4 mo postinjection. Viral
      injection of IGF-IB produced two- to sevenfold more IGF-I than rAAVIGF-IA.
      Hypertrophy was observed 2 and 4 mo postinjection, where both rAAVIGF-IA and
      rAAVIGF-IB were equally effective in increasing muscle mass. These results
      suggest that there is a threshold of IGF-I production necessary to promote muscle
      hypertrophy in young growing animals regardless of isoform. In 6-mo-old animals,
      only rAAVIGF-IA produced significant increases in muscle size, even though
      increased IGF-I content was observed after injection of both isoforms. Therefore,
      the ability for IGF-IB to promote muscle hypertrophy is only effective in growing
      animals, suggesting that the bioavailability of this isoform or its receptor
      affinity diminishes with age.

PMID- 16439514
TI  - Strain-specific differences in sensitivity to ischemia-reperfusion lung injury in
      mice.
AB  - Ischemia-reperfusion (I/R) lung injury is characterized by increased pulmonary
      endothelial permeability and edema, but the genetic basis for this injury is
      unknown. We utilized an in vivo mouse preparation of unilateral lung I/R to
      evaluate the genetic determinants of I/R lung injury. An index of pulmonary
      vascular protein permeability was measured by the ratio of left-to-right lung
      Evans blue dye of eight inbred mouse strains after 30 min of left lung ischemia
      and 150 min of reperfusion. The order of strain-specific sensitivity to I/R lung
      injury was BALB/c < SJL/J < CBA/J < C57BL/6J < 129/J < A/J < C3H/H3J < SWR/J. The
      reciprocal F1 offspring of the BALB/c and SWR/J progenitor strains had
      intermediate phenotypes but a differing variance. A similar pattern of right lung
      Evans blue dye content suggested the presence of contralateral injury because
      baseline vascular permeability was not different. Lung I/R injury was attenuated
      by NADPH oxidase inhibition, indicating a role for NADPH oxidase-derived reactive
      oxygen species (ROS). There was no strain-dependent difference in lung NADPH
      oxidase expression. Strain-related differences in zymosan-stimulated neutrophil
      ROS production did not correlate with I/R lung injury in that neutrophil ROS
      production in SWR/J mice was greater than C57BL/6J but not different from BALB/c
      mice. These data indicate the presence of a genetic sensitivity to lung I/R
      injury that involves multiple genes including a maternal-related factor. Although
      neutrophil-derived ROS production is also modulated by genetic factors, the
      pattern did not explain the genetic sensitivity to lung I/R injury.

PMID- 16439515
TI  - Organ and effective dose evaluation in diagnostic radiology based on in-phantom
      dose measurements with novel photodiode-dosemeters.
AB  - Organ and the effective doses of patients undergoing clinical X ray examinations
      of chest and abdomen were evaluated with an anthropomorphic phantom and a new
      dosimetry system. The system was comprised of 34 pin photodiode dosemeters placed
      in/on particular tissues or organs of the anthropomorphic phantom, where the
      tissues and organs are defined by the International Commission on Radiological
      Protection (ICRP) to estimate the effective doses. Dosemeter signals were
      acquired on a personal computer directly, and converted into absorbed doses, from
      which the organ and the effective doses were evaluated on the computer. Our study
      showed that organ doses ranged from <0.01 to 0.72 mGy in routine X-ray
      radiography of chest and of abdomen and from 0.07 to 55.91 mGy in routine
      computed tomography (CT) examinations with current multi-slice CT scanners. The
      effective dose observed in the chest CT examination was approximately 300 times
      higher than that in chest radiography.

PMID- 16439516
TI  - Influence of patient thickness and operation modes on occupational and patient
      radiation doses in interventional cardiology.
AB  - Patient and staff dose values in an interventional cardiology laboratory for
      different operational modes and several patient thicknesses (from 16 to 28 cm,
      simulated using polymethylmethacrylate) are presented. When increasing patient
      thicknesses and depending on fluoroscopy and cine modes, occupational doses can
      increase >30 times the baseline level. Scatter dose rates at the cardiologist's
      position with no radiation protective tools ranged from 1 to 14 mSv h(-1) for
      fluoroscopy, and from 10 to 47 mSv h(-1) during cine acquisition. Patient
      entrance surface air kerma rates increased by nearly 3 and staff dose rates by up
      to 2.6 when fluoroscopy was moved from the low to the high mode, for a typical 20
      cm thickness. The respective increase factors were 6 and 4.2 when patient
      thickness rose from 16 to 28 cm, and by 10 and 8.3, when comparing cine
      acquisition with the low fluoroscopy mode. The knowledge of typical dose rates
      for each X-ray system in use in catheterisation laboratories is essential in
      order to optimise protection of patients and staff.

PMID- 16439517
TI  - Dose constraints and guidance for exposure of individuals knowingly and willingly
      helping in the support and comfort of individuals undergoing medical exposure.
AB  - The council of the European Union (EU) has adopted directive 97/43/EURATOM that
      states that Member States shall ensure that dose constraints are established for
      exposure of those individuals (voluntary helpers) knowingly and willingly helping
      patients undergoing medical diagnosis or treatment. This study investigates for
      which medical diagnoses and treatments voluntary helpers are active. It provides
      a rough estimation of the effective dose to the voluntary helper for various
      applications. It summarises the dose constraints established in various EU Member
      States. Voluntary helpers are especially active in paediatric radiology and in
      nuclear medicine for both diagnostic and for therapeutic purposes. No voluntary
      helpers are active during radiotherapy. Voluntary helpers are commonly one of the
      parents, relatives or friends of the patient. In The Netherlands, the highest
      effective dose to voluntary helpers of approximately 2.3 mSv is found for therapy
      of patients younger than 1 y with metaiodobenzylguanidine labelled with 131I.
      Effective doses to voluntary helpers in paediatric radiology are, generally,
      quite small, i.e. lower than several tens of microSv at maximum without wearing
      protective clothing.

PMID- 16439518
TI  - Envelope determinants for dual-receptor specificity in feline leukemia virus
      subgroup A and T variants.
AB  - Gammaretroviruses, including the subgroups A, B, and C of feline leukemia virus
      (FeLV), use a multiple-membrane-spanning transport protein as a receptor. In some
      cases, such as FeLV-T, a nonclassical receptor that includes both a transport
      protein (Pit1) and a soluble cofactor (FeLIX) is required for entry. To define
      which regions confer specificity to classical versus nonclassical receptor
      pathways, we engineered mutations found in either FeLV-A/T or FeLV-T,
      individually and in combination, into the backbone of the transmissible form of
      the virus, FeLV-A. The receptor specificities of these viruses were tested by
      measuring infection and binding to cells expressing the FeLV-A receptor or the
      FeLV-T receptors. FeLV-A receptor specificity was maintained when changes at
      amino acid position 6, 7, or 8 of the mature envelope glycoprotein were
      introduced, although differences in infection efficiency were observed. When
      these N-terminal mutations were introduced together with a C-terminal 4-amino
      acid insertion and an adjacent amino acid change, the resulting viruses acquired
      FeLV-T receptor specificity. Additionally, a W-->L change at amino acid position
      378, although not required, enhanced infectivity for some viruses. Thus, we have
      found that determinants in the N and C termini of the envelope surface unit can
      direct entry via the nonclassical FeLV-T receptor pathway. The region that has
      been defined as the receptor binding domain of gammaretroviral envelope proteins
      determined entry via the FeLV-A receptor independently of the presence of the N-
      and C-terminal FeLV-T receptor determinants.

PMID- 16439519
TI  - Respiratory viruses augment the adhesion of bacterial pathogens to respiratory
      epithelium in a viral species- and cell type-dependent manner.
AB  - Secondary bacterial infections often complicate respiratory viral infections, but
      the mechanisms whereby viruses predispose to bacterial disease are not completely
      understood. We determined the effects of infection with respiratory syncytial
      virus (RSV), human parainfluenza virus 3 (HPIV-3), and influenza virus on the
      abilities of nontypeable Haemophilus influenzae and Streptococcus pneumoniae to
      adhere to respiratory epithelial cells and how these viruses alter the expression
      of known receptors for these bacteria. All viruses enhanced bacterial adhesion to
      primary and immortalized cell lines. RSV and HPIV-3 infection increased the
      expression of several known receptors for pathogenic bacteria by primary
      bronchial epithelial cells and A549 cells but not by primary small airway
      epithelial cells. Influenza virus infection did not alter receptor expression.
      Paramyxoviruses augmented bacterial adherence to primary bronchial epithelial
      cells and immortalized cell lines by up-regulating eukaryotic cell receptors for
      these pathogens, whereas this mechanism was less significant in primary small
      airway epithelial cells and in influenza virus infections. Respiratory viruses
      promote bacterial adhesion to respiratory epithelial cells, a process that may
      increase bacterial colonization and contribute to disease. These studies
      highlight the distinct responses of different cell types to viral infection and
      the need to consider this variation when interpreting studies of the interactions
      between respiratory cells and viral pathogens.

PMID- 16439520
TI  - Human immunodeficiency virus type 1 env evolves toward ancestral states upon
      transmission to a new host.
AB  - Selecting human immunodeficiency virus (HIV) sequences for inclusion within
      vaccines has been a difficult problem, as circulating HIV strains evolve
      relentlessly and become increasingly divergent over time. We report an assessment
      of this divergence from three perspectives: (i) across different hosts as a
      function of time of infection, (ii) between donors and recipients in known
      transmission pairs, and (iii) within individual hosts over time in relation to
      the initially replicating virus and to the deduced ancestral sequence of the
      intrahost viral population. Surprisingly, we consistently found less divergence
      between viruses from different individuals sampled in primary infection than in
      individuals sampled at more advanced stages of illness. Furthermore, longitudinal
      analysis of intrahost divergence revealed a 2- to 3-year period of evolution
      toward a common ancestral sequence at the start of infection, indicating that HIV
      recovers certain ancestral features when infecting a new host. These results have
      important implications for the study of HIV population genetics and rational
      vaccine design, including favoring the inclusion of viral gene sequences taken
      early in infection.

PMID- 16439521
TI  - Generation of CD8+ T-cell responses by a recombinant nonpathogenic Mycobacterium
      smegmatis vaccine vector expressing human immunodeficiency virus type 1 Env.
AB  - Because the vaccine vectors currently being evaluated in human populations all
      have significant limitations in their immunogenicity, novel vaccine strategies
      are needed for the elicitation of cell-mediated immunity. The nonpathogenic,
      rapidly growing mycobacterium Mycobacterium smegmatis was engineered as a vector
      expressing full-length human immunodeficiency virus type 1 (HIV-1) HXBc2 envelope
      protein. Immunization of mice with recombinant M. smegmatis led to the expansion
      of major histocompatibility complex class I-restricted HIV-1 epitope-specific
      CD8(+) T cells that were cytolytic and secreted gamma interferon. Effector and
      memory T lymphocytes were elicited, and repeated immunization generated a stable
      central memory pool of virus-specific cells. Importantly, preexisting immunity to
      Mycobacterium bovis BCG had only a marginal effect on the immunogenicity of
      recombinant M. smegmatis. This mycobacterium may therefore be a useful vaccine
      vector.

PMID- 16439522
TI  - Site-directed mutagenesis of the Nidovirus replicative endoribonuclease NendoU
      exerts pleiotropic effects on the arterivirus life cycle.
AB  - The highly conserved NendoU replicative domain of nidoviruses (arteriviruses,
      coronaviruses, and roniviruses) belongs to a small protein family whose cellular
      branch is prototyped by XendoU, a Xenopus laevis endoribonuclease involved in
      nucleolar RNA processing. Recently, sequence-specific in vitro endoribonuclease
      activity was demonstrated for the NendoU-containing nonstructural protein (nsp)
      15 of several coronaviruses. To investigate the biological role of this novel
      enzymatic activity, we have characterized a comprehensive set of arterivirus
      NendoU mutants. Deleting parts of the NendoU domain from nsp11 of equine
      arteritis virus was lethal. Site-directed mutagenesis of conserved residues
      exerted pleiotropic effects. In a first-cycle analysis, replacement of two
      conserved Asp residues in the C-terminal part of NendoU rendered viral RNA
      synthesis and virus production undetectable. In contrast, mutagenesis of other
      conserved residues, including two putative catalytic His residues that are
      absolutely conserved in NendoU and cellular homologs, produced viable mutants
      displaying reduced plaque sizes (20 to 80% reduction) and reduced yields of
      infectious progeny of up to 5 log units. A more detailed analysis of these
      mutants revealed a moderate reduction in RNA synthesis, with subgenomic RNA
      synthesis consistently being more strongly affected than genome replication. Our
      data suggest that the arterivirus nsp11 is a multifunctional protein with a key
      role in viral RNA synthesis and additional functions in the viral life cycle that
      are as yet poorly defined.

PMID- 16439523
TI  - Poliovirus protein 3AB displays nucleic acid chaperone and helix-destabilizing
      activities.
AB  - Poliovirus protein 3AB displayed nucleic acid chaperone activity in promoting the
      hybridization of complementary nucleic acids and destabilizing secondary
      structure. Hybridization reactions at 30 degrees C between 20- and 40-nucleotide
      RNA oligonucleotides and 179- or 765-nucleotide RNAs that contained a
      complementary region were greatly enhanced in the presence of 3AB. The effect was
      nonspecific as reactions between DNA oligonucleotides and RNA or DNA templates
      were also enhanced. Reactions were optimal with 1 mM MgCl(2) and 20 mM KCl.
      Analysis of the reactions with various 3AB and template concentrations indicated
      that enhancement required a critical amount of 3AB that increased as the
      concentration of nucleic acid increased. This was consistent with a requirement
      for 3AB to "coat" the nucleic acids for enhancement. The helix-destabilizing
      activity of 3AB was tested in an assay with two 42-nucleotide completely
      complementary DNAs. Each complement formed a strong stem-loop (DeltaG = -7.2
      kcal/mol) that required unwinding for hybridization to occur. DNAs were modified
      at the 3' or 5' end with fluorescent probes such that hybridization resulted in
      quenching of the fluorescent signal. Under optimal conditions at 30 degrees C,
      3AB stimulated hybridization in a concentration-dependent manner, as did human
      immunodeficiency virus nucleocapsid protein, an established chaperone. The
      results are discussed with respect to the role of 3AB in viral replication and
      recombination.

PMID- 16439524
TI  - Efficient site-specific integration of large transgenes by an enhanced herpes
      simplex virus/adeno-associated virus hybrid amplicon vector.
AB  - We previously demonstrated that a herpes simplex virus type 1 (HSV-1)/adeno
      associated virus (AAV) hybrid amplicon vector constructed by inserting the
      sequences of regulatory protein (rep) and inverted terminal repeats of AAV into
      an HSV amplicon vector resulted in the enhanced stability of transgene expression
      compared to the original HSV-1 amplicon vector. However, problems related to the
      expression of Rep compromised its therapeutic applications. We report here a new
      HSV/AAV hybrid amplicon vector system that not only solved problems associated
      with Rep expression but also markedly improved the stable transduction efficiency
      of this vector. This new HSV/AAV vector is designed in a way that little or no
      Rep would be expressed in packaging cells, but it can be expressed in transduced
      cells if Cre recombinase is provided. Furthermore, Rep expression will be
      automatically suppressed as a consequence of Rep-mediated integration. Our
      results showed that the new hybrid amplicon vector yielded titers comparable to
      those of standard amplicon vectors. When Cre-expressing 293 cells were
      transduced, a low level of Rep expression was detected, and stable transduction
      was achieved in approximately 22% of transduced cells; of those cells,
      approximately 70% transduction was achieved by Rep-mediated site-specific
      integration. In the majority of the stably transduced cells, Rep expression was
      no longer observed. Our results also proved that this vector system is capable of
      efficiently accommodating and site-specifically integrating large transgenes,
      such as the full-length dystrophin expression cassette. Thus, the new HSV/AAV
      vector demonstrated unique advantages in safe and effective delivery of long
      lasting transgene expression into human cells.

PMID- 16439525
TI  - Structure-function analysis of the epitope for 4E10, a broadly neutralizing human
      immunodeficiency virus type 1 antibody.
AB  - The human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 4E10 binds
      to a linear, highly conserved epitope within the membrane-proximal external
      region of the HIV-1 envelope glycoprotein gp41. We have delineated the peptide
      epitope of the broadly neutralizing 4E10 antibody to gp41 residues 671 to 683,
      using peptides with different lengths encompassing the previously suggested core
      epitope (NWFDIT). Peptide binding to the 4E10 antibody was assessed by
      competition enzyme-linked immunosorbent assay, and the K(d) values of selected
      peptides were determined using surface plasmon resonance. An Ala scan of the
      epitope indicated that several residues, W672, F673, and T676, are essential
      (>1,000-fold decrease in binding upon replacement with alanine) for 4E10
      recognition. In addition, five other residues, N671, D674, I675, W680, and L679,
      make significant contributions to 4E10 binding. In general, the Ala scan results
      agree well with the recently reported crystal structure of 4E10 in complex with a
      13-mer peptide and with our circular dichroism analyses. Neutralization
      competition assays confirmed that the peptide NWFDITNWLWYIKKKK-NH(2) could
      effectively inhibit 4E10 neutralization. Finally, to limit the conformational
      flexibility of the peptides, helix-promoting 2-aminoisobutyric acid residues and
      helix-inducing tethers were incorporated. Several peptides have significantly
      improved affinity (>1,000-fold) over the starting peptide and, when used as
      immunogens, may be more likely to elicit 4E10-like neutralizing antibodies.
      Hence, this study represents the first stage toward iterative development of a
      vaccine based on the 4E10 epitope.

PMID- 16439526
TI  - A novel adenovirus type 6 (Ad6)-based hepatitis C virus vector that overcomes
      preexisting anti-ad5 immunity and induces potent and broad cellular immune
      responses in rhesus macaques.
AB  - Success in resolving hepatitis C virus (HCV) infection has been correlated to
      vigorous, multispecific, and sustained CD8(+) T-cell response in humans and
      chimpanzees. The efficacy of inducing T-cell-mediated immunity by recombinant
      serotype 5 adenovirus vector has been proven in many animal models of infectious
      diseases, but its immunogenicity can be negatively influenced by preexisting
      immunity against the vector itself. To evaluate the less prevalent adenovirus
      serotype 6 (Ad6) as an alternative vector for and HCV vaccine development, we
      have generated serotype 5 and 6 adenoviral vectors directing expression of the
      nonstructural region of HCV (MRKAd5-NSmut and MRKAd6-NSmut). Immunogenicity
      studies in mice showed that the two vectors induced comparable T-cell responses
      but that only MRKAd6-NSmut was not suppressed in the presence of anti-Ad5
      immunity. In contrast, preexisting anti-Ad5 immunity dramatically blunted the
      immunogenicity of the serotype 5-based HCV vector. Furthermore, MRKAd6-NSmut
      showed equivalent potency, breadth, and longevity of HCV-specific T-cell
      responses in rhesus macaques as the corresponding Ad5-based vector over a wide
      range of doses and was capable of boosting DNA-primed animals even if
      administered at low doses. These data support the use of the MRKAd6-NSmut for
      anti-HCV immunotherapy and, more generally, for the Ad6 serotype as a better
      genetic vaccine vehicle than Ad5.

PMID- 16439527
TI  - Function of small hydrophobic proteins of paramyxovirus.
AB  - Mumps virus (MuV), a rubulavirus of the paramyxovirus family, causes acute
      infections in humans. MuV has seven genes including a small hydrophobic (SH)
      gene, which encodes a type I membrane protein of 57 amino acid residues. The
      function of the SH protein is not clear, although its expression is not necessary
      for growth of MuV in tissue culture cells. It is speculated that MuV SH plays a
      role in viral pathogenesis. Simian virus 5 (SV5), a closely related rubulavirus,
      encodes a 44-amino-acid-residue SH protein. Recombinant SV5 lacking the SH gene
      (rSV5DeltaSH) is viable and has no growth defect in tissue culture cells.
      However, rSV5DeltaSH induces apoptosis in tissue culture cells and is attenuated
      in vivo. Neutralizing antibodies against tumor necrosis factor alpha (TNF-alpha)
      and TNF-alpha receptor 1 block rSV5DeltaSH-induced apoptosis, suggesting that SV5
      SH plays an essential role in blocking the TNF-alpha-mediated apoptosis pathway.
      Because MuV is closely related to SV5, we hypothesize that the SH protein of MuV
      has a function similar to that of SV5, even though there is no sequence homology
      between them. To test this hypothesis and to study the function of MuV SH, we
      have replaced the open reading frame (ORF) of SV5 SH with the ORF of MuV SH in a
      SV5 genome background. The recombinant SV5 (rSV5DeltaSH+MuV-SH) was analyzed in
      comparison with SV5. It was found that rSV5DeltaSH+MuV-SH was viable and behaved
      like wild-type SV5, suggesting that MuV SH has a function similar to that of SV5
      SH. Furthermore, both ectopically expressed SV5 SH and MuV SH blocked activation
      of NF-kappaB by TNF-alpha in a reporter gene assay, suggesting that both SH
      proteins can inhibit TNF-alpha signaling.

PMID- 16439529
TI  - Characterization of the role of very late expression factor 1 in baculovirus
      capsid structure and DNA processing.
AB  - Very late expression factor 1 (VLF-1) of Autographa californica multiple
      nucleopolyhedrovirus is a putative tyrosine recombinase and is required for both
      very late gene expression and budded virus production. In this report, we show
      that a vlf-1 knockout bacmid was able to synthesize viral DNA at levels similar
      to that detected for a gp64 knockout bacmid that served as a noninfectious
      control virus. Additionally, analysis of replicated bacmid DNA by field-inversion
      gel electrophoresis indicated that VLF-1 is not required for synthesizing high
      molecular-weight intermediates that could be resolved into unit-length genomes
      when cut at a unique restriction site. However, immunoelectron microscopic
      analysis revealed that in cells transfected with a vlf-1 knockout bacmid,
      aberrant tubular structures containing the capsid protein vp39 were observed,
      suggesting that this virus construct was defective in producing mature capsids.
      In contrast, rescuing the vlf-1 knockout bacmid construct with a copy of VLF-1
      that carries a mutation of a highly conserved tyrosine (Y355F) was sufficient to
      restore the production of nucleocapsids with a normal appearance, but not
      infectious virus production. Furthermore, the results of a DNase I protection
      assay indicated that the DNA packaging efficiency of the VLF-1(Y355F) virus
      construct was similar to that of the gp64 knockout control. Finally, a
      recombinant virus containing a functional hemagglutinin epitope-tagged version of
      VLF-1 was constructed to investigate the association of VLF-1 with the
      nucleocapsid. Analysis by immunoelectron microscopy of Sf-9 cells infected with
      this virus showed that VLF-1 localized to an end region of the nucleocapsid.
      Collectively, these results indicate that VLF-1 is required for normal capsid
      assembly and serves an essential function during the final stages of the DNA
      packaging process.

PMID- 16439528
TI  - Phosphorylation of the varicella-zoster virus (VZV) major transcriptional
      regulatory protein IE62 by the VZV open reading frame 66 protein kinase.
AB  - IE62, the major transcriptional regulatory protein encoded by varicella-zoster
      virus (VZV), is nuclear at early times of VZV infection but then becomes
      predominantly cytoplasmic as a result of expression of the protein kinase encoded
      by open reading frame 66 (ORF66). Cytoplasmic forms of IE62 are required for its
      inclusion as an abundant VZV virion tegument protein. Here we show that ORF66
      directly phosphorylates IE62 at two residues, with phosphorylation at S686 being
      sufficient to regulate IE62 nuclear import. Phosphotryptic peptide analyses
      established an ORF66 kinase-mediated phosphorylation of the complete IE62 protein
      in transfected and VZV-infected cells. Using truncated and point-mutated IE62
      peptides, ORF66-directed phosphorylation was mapped to residues S686 and S722,
      immediately downstream of the IE62 nuclear localization signal. An IE62 protein
      with an S686A mutation retained efficient nuclear import activity, even in the
      presence of functional ORF66 protein kinase, but an IE62 protein containing an
      S686D alteration was imported into the nucleus inefficiently. In contrast, the
      nuclear import of IE62 carrying an S722A mutation was still modulated by ORF66
      expression, and IE62 with an S722D mutation was imported efficiently into the
      nucleus. An in vitro phosphorylation assay was developed using bacterially
      expressed IE62-maltose binding protein fusions as substrates for immunopurified
      ORF66 protein kinase from recombinant baculovirus-infected insect cells. ORF66
      kinase phosphorylated the IE62 peptides, with similar specificities for residues
      S686 and S722. These results indicate that IE62 nuclear import is modulated as a
      result of direct phosphorylation of IE62 by ORF66 kinase. This represents an
      interaction that is, so far, unique among the alphaherpesviruses.

PMID- 16439530
TI  - Time- and temperature-dependent activation of hepatitis C virus for low-pH
      triggered entry.
AB  - Hepatitis C virus (HCV) is an important human pathogen associated with chronic
      liver disease. Recently, based on a genotype 2a isolate, tissue culture systems
      supporting complete replication and infectious virus production have been
      developed. In this study, we used cell culture-produced infectious HCV to analyze
      the viral entry pathway into Huh-7.5 cells. Bafilomycin A1 and concanamycin A,
      inhibitors of vacuolar ATPases, prevented HCV entry when they were present prior
      to infection and had minimal effect on downstream replication events. HCV entry
      therefore appears to be pH dependent, requiring an acidified intracellular
      compartment. For many other enveloped viruses, acidic pH triggers an irreversible
      conformational change, which promotes virion-endosomal membrane fusion. Such
      viruses are often inactivated by low pH. In the case of HCV, exposure of virions
      to acidic pH followed by return to neutral pH did not affect their infectivity.
      This parallels the observation made for the related pestivirus bovine viral
      diarrhea virus. Low pH could activate the entry of cell surface-bound HCV but
      only after prolonged incubation at 37 degrees C. This suggests that there are
      rate-limiting, postbinding events that are needed to render HCV competent for low
      pH-triggered entry. Such events may involve interaction with a cellular
      coreceptor or other factors but do not require cathepsins B and L, late endosomal
      proteases that activate Ebola virus and reovirus for entry.

PMID- 16439531
TI  - Comprehensive mapping of receptor-functioning domains in feline leukemia virus
      subgroup C receptor FLVCR1.
AB  - Infection of cells by the highly anemogenic feline leukemia virus subgroup C
      (FeLV-C) is mediated by the heme exporter FLVCR1, a cell surface protein
      containing 12 potential transmembrane segments with six presumptive extracellular
      loops (ECLs). To identify FLVCR1 residues critical for mediating FeLV-C
      infection, we first independently isolated a human cDNA encoding the FLVCR2
      protein that shares 52% identity to human FLVCR1, and we show that FLVCR2 does
      not function as a receptor for FeLV-C. Then, by generating specific hybrids
      between FLVCR1 and FLVCR2 and testing susceptibility of mouse cells expressing
      these hybrids to beta-galactosidase encoding FeLV-C, we identify FLVCR1 ECLs 1
      and 6 as critical for mediating FeLV-C infection. Mouse cells expressing a hybrid
      protein containing FLVCR2 backbone with the ECL6 sequence from FLVCR1 were highly
      susceptible to FeLV-C infection. Using site-directed mutagenesis, we show that a
      single mutation of Asn463 in FLVCR2 ECL6 to an acidic Asp residue (a residue
      present in the corresponding position 487 in FLVCR1 ECL6) is sufficient to render
      FLVCR2 functional as an FeLV-C receptor. However, an Asp487Asn mutation in FLVCR1
      ECL6 or substitution of the entire FLVCR1 ECL6 sequence for FLVCR2 ECL6 sequence
      does not disrupt receptor function. Subsequent substitutions show that residues
      within FLVCR1 ECL1 also contribute to mediating FeLV-C infection. Furthermore,
      our results suggest that FLVCR1 regions that mediate FeLV-C surface unit binding
      are distinct from ECL1 and ECL6. Our results are consistent with previous
      conclusions that infection of cells by gammaretroviruses involves interaction of
      virus with multiple receptor regions.

PMID- 16439532
TI  - Rectal immunization with rotavirus virus-like particles induces systemic and
      mucosal humoral immune responses and protects mice against rotavirus infection.
AB  - To evaluate whether the rectal route of immunization may be used to provide
      appropriate protection against enteric pathogens such as rotaviruses (RV), we
      studied the antibody response and the protection induced by rectal immunization
      of mice with RV virus-like particles (VLP). For this purpose, 6-week-old BALBc
      mice were rectally immunized twice with RV 8-2/6/7-VLP derived from the bovine RV
      RF81 strain either alone or combined with various adjuvants including four toxins
      [cholera toxin (CT) and three attenuated Escherichia coli-derived heat-labile
      toxins (LTs), LT(R192G), LT(R72), and LT(K63)] and two Toll-like receptor
      targeting adjuvants (CpG and resiquimod). Six weeks after the second
      immunization, mice were challenged with murine RV strain ECw. RV VLP administered
      alone were not immunogenic and did not protect mice against RV challenge. By
      contrast, RV VLP combined with any of the toxin adjuvants were immunogenic (mice
      developed significant titers of anti-RV immunoglobulin A [IgA] in both serum and
      feces and of anti-RV IgG in serum) and either efficiently induced complete
      protection of the mice (no detectable fecal virus shedding) or, for LT(K63),
      reduced the amount of fecal virus shedding after RV challenge. When combined with
      RV VLP, CpG and resiquimod failed to achieve protection, although CpG efficiently
      induced an antibody response to RV. These results support the consideration of
      the rectal route for the development of new immunization strategies against RV
      infection. Rectal delivery of a VLP-based vaccine might allow the use of
      adjuvants less toxic than, but as efficient as, CT.

PMID- 16439533
TI  - Multimeric soluble CD40 ligand and GITR ligand as adjuvants for human
      immunodeficiency virus DNA vaccines.
AB  - For use in humans, human immunodeficiency virus (HIV) DNA vaccines may need to
      include immunostimulatory adjuvant molecules. CD40 ligand (CD40L), a member of
      the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant,
      but it has been difficult to use because it is normally expressed as a trimeric
      membrane molecule. Soluble trimeric forms of CD40L have been produced, but in
      vitro data indicate that multimeric, many-trimer forms of soluble CD40L are more
      active. This multimerization requirement was evaluated in mice using plasmids
      that encoded either 1-trimer, 2-trimer, or 4-trimer soluble forms of CD40L.
      Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion
      with the body of surfactant protein D was used to produce the 4-trimer form.
      Using plasmids for secreted HIV-1 antigens Gag and Env, soluble CD40L was active
      as an adjuvant in direct proportion to the valence of the trimers (1 < 2 < 4).
      These CD40L-augmented DNA vaccines elicited strong CD8(+) T-cell responses but
      did not elicit significant CD4(+) T-cell or antibody responses. To test the
      applicability of the multimeric fusion protein approach to other TNFSFs, a 4
      trimer construct for the ligand of glucocorticoid-induced TNF family-related
      receptor (GITR) was also prepared. Multimeric soluble GITR ligand (GITRL)
      augmented the CD8(+) T-cell, CD4(+) T-cell, and antibody responses to DNA
      vaccination. In summary, multimeric CD40L and GITRL are new adjuvants for DNA
      vaccines. Plasmids for expressing multimeric TNFSF fusion proteins permit the
      rapid testing of TNFSF molecules in vivo.

PMID- 16439534
TI  - Transcriptome signature of virulent and attenuated pseudorabies virus-infected
      rodent brain.
AB  - Mammalian alphaherpesviruses normally establish latent infections in ganglia of
      the peripheral nervous system in their natural hosts. Occasionally, however,
      these viruses spread to the central nervous system (CNS), where they cause
      damaging, often fatal, infections. Attenuated alphaherpesvirus derivatives have
      been used extensively as neuronal circuit tracers in a variety of animal models.
      Their circuit-specific spread provides a unique paradigm to study the local and
      global CNS response to infection. Thus, we systematically analyzed the host gene
      expression profile after acute pseudorabies virus (PRV) infection of the CNS
      using Affymetrix GeneChip technology. Rats were injected intraocularly with one
      of three selected virulent and attenuated PRV strains. Relative levels of
      cellular transcripts were quantified from hypothalamic and cerebellar tissues at
      various times postinfection. The number of cellular genes responding to infection
      correlated with the extent of virus dissemination and relative virulence of the
      PRV strains. A total of 245 out of 8,799 probe sets, corresponding to 182 unique
      cellular genes, displayed increased expression ranging from 2- to more than 100
      fold higher than in uninfected tissue. Over 60% thereof were categorized as
      immune, proinflammatory, and other cellular defense genes. Additionally, a large
      fraction of infection-induced transcripts represented cellular stress responses,
      including glucocorticoid- and redox-related pathways. This is the first
      comprehensive in vivo analysis of the global transcriptional response of the
      mammalian CNS to acute alphaherpesvirus infection. The differentially regulated
      genes reported here are likely to include potential diagnostic and therapeutic
      targets for viral encephalitides and other neurodegenerative or neuroinflammatory
      diseases.

PMID- 16439535
TI  - Regulation of human papillomavirus type 16 E7 activity through direct protein
      interaction with the E2 transcriptional activator.
AB  - In order to ensure a productive life cycle, human papillomaviruses (HPVs) require
      fine regulation of their gene products. Uncontrolled activity of the viral
      oncoproteins E6 and E7 results in the immortalization of the infected epithelial
      cells and thus prevents the production of mature virions. Ectopically expressed
      E2 has been shown to suppress transcription of the HPV E6 and E7 region in cell
      lines where the viral DNA is integrated into the host genome, resulting in growth
      inhibition. However, it has been demonstrated that growth control of these cell
      lines can also occur independently of HPV E2 transcriptional activity in high
      risk HPV types. In addition, E2 is unable to suppress transcription of the same
      region in cell lines derived from cervical tumors that harbor only episomal
      copies of the viral DNA. Here we show that HPV type 16 (HPV-16) E2 is capable of
      inhibiting HPV-16 E7 cooperation with an activated ras oncogene in the
      transformation of primary rodent cells. Furthermore, we demonstrate a direct
      interaction between the E2 and E7 proteins which requires the hinge region of E2
      and the zinc-binding domain of E7. These viral proteins interact in vivo, and E2
      has a marked effect upon both the stability of E7 and its cellular location,
      where it is responsible for recruiting E7 onto mitotic chromosomes at the later
      stages of mitosis. These results demonstrate a direct role for E2 in regulating
      the function of E7 and suggest an important role for E2 in directing E7
      localization during mitosis.

PMID- 16439536
TI  - Importin-beta family members mediate alpharetrovirus gag nuclear entry via
      interactions with matrix and nucleocapsid.
AB  - The retroviral Gag polyprotein orchestrates the assembly and release of virus
      particles from infected cells. We previously reported that nuclear transport of
      the Rous sarcoma virus (RSV) Gag protein is intrinsic to the virus assembly
      pathway. To identify cis- and trans-acting factors governing nucleocytoplasmic
      trafficking, we developed novel vectors to express regions of Gag in
      Saccharomyces cerevisiae. The localization of Gag proteins was examined in the
      wild type and in mutant strains deficient in members of the importin-beta family.
      We confirmed the Crm1p dependence of the previously identified Gag p10 nuclear
      export signal. The known nuclear localization signal (NLS) in MA (matrix) was
      also functional in S. cerevisiae, and additionally we discovered a novel NLS
      within the NC (nucleocapsid) domain of Gag. MA utilizes Kap120p and Mtr10p import
      receptors while nuclear entry of NC involves the classical importin-alpha/beta
      (Kap60p/95p) pathway. NC also possesses nuclear targeting activity in avian cells
      and contains the primary signal for the import of the Gag polyprotein. Thus, the
      nucleocytoplasmic dynamics of RSV Gag depend upon the counterbalance of Crm1p
      mediated export with two independent NLSs, each interacting with distinct nuclear
      import factors.

PMID- 16439537
TI  - Hyperphosphorylation of the rotavirus NSP5 protein is independent of serine 67,
      [corrected] NSP2, or [corrected] the intrinsic insolubility of NSP5 is regulated
      by cellular phosphatases.
AB  - The NSP5 protein is required for viroplasm formation during rotavirus infection
      and is hyperphosphorylated into 32- to 35-kDa isoforms. Earlier studies reported
      that NSP5 is not hyperphosphorylated without NSP2 coexpression or deleting the
      NSP5 N terminus and that serine 67 is essential for NSP5 hyperphosphorylation. In
      this report, we show that full-length NSP5 is hyperphosphorylated in the absence
      of NSP2 or serine 67 and demonstrate that hyperphosphorylated NSP5 is
      predominantly present in previously unrecognized cellular fractions that are
      insoluble in 0.2% sodium dodecyl sulfate. The last 68 residues of NSP5 are
      sufficient to direct green fluorescent protein into insoluble fractions and cause
      green fluorescent protein localization into viroplasm-like structures; however,
      NSP5 insolubility was intrinsic and did not require NSP5 hyperphosphorylation.
      When we mutated serine 67 to alanine we found that the NSP5 mutant was both
      hyperphosphorylated and insoluble, identical to unmodified NSP5, and as a result
      serine 67 is not required for NSP5 phosphorylation. Interestingly, treating cells
      with the phosphatase inhibitor calyculin A permitted the accumulation of soluble
      hyperphosphorylated NSP5 isoforms. This suggests that soluble NSP5 is
      constitutively dephosphorylated by cellular phosphatases and demonstrates that
      hyperphosphorylation does not direct NSP5 insolubility. Collectively these
      findings indicate that NSP5 hyperphosphorylation and insolubility are completely
      independent parameters and that analyzing insoluble NSP5 is essential for studies
      assessing NSP5 phosphorylation. Our results also demonstrate the involvement of
      cellular phosphatases in regulating NSP5 phosphorylation and indicate that in the
      absence of other rotavirus proteins, domains on soluble and insoluble NSP5
      recruit cellular kinases and phosphatases that coordinate NSP5
      hyperphosphorylation.

PMID- 16439538
TI  - Functional analysis of hepatitis C virus envelope proteins, using a cell-cell
      fusion assay.
AB  - Hepatitis C virus (HCV) envelope proteins mediate the entry of virus into cells
      by binding to cellular receptors, resulting in fusion of the viral membrane with
      the host cell membrane and permitting the viral genome to enter the cytoplasm. We
      report the development of a robust and reproducible cell-cell fusion assay using
      envelope proteins from commonly occurring genotypes of HCV. The assay scored HCV
      envelope protein-mediated fusion by the production of fluorescent green syncytia
      and allowed us to elucidate many aspects of HCV fusion, including the pH of
      fusion, cell types that permit viral entry, and the conformation of envelope
      proteins essential for fusion. We found that fusion could be specifically
      inhibited by anti-HCV antibodies and by at least one peptide. We also generated a
      number of insertional mutations in the envelope proteins and tested nine of these
      using the fusion assay. We demonstrate that this fusion assay is a powerful tool
      for understanding the mechanism of HCV-mediated fusion, elucidating mutant
      function, and testing antiviral agents.

PMID- 16439539
TI  - Pulmonary immunity to viral infection: adenovirus infection of lung dendritic
      cells renders T cells nonresponsive to interleukin-2.
AB  - Adenovirus (Ad) infection has been identified as predisposing hosts to the
      development of pulmonary disease through unknown mechanisms. Lung dendritic cells
      (DCs) are vital for initiating pulmonary immune responses; however, the effects
      of Ad infection on primary lung DC have not been studied. In contrast to the
      effects on bone marrow- and monocyte-derived DCs, the current study shows that Ad
      infection of murine BALB/c lung DCs in vitro and in vivo suppresses DC-induced T
      cell proliferation. The effect of Ad on DCs was not due to a downregulation of
      major histocompatibility complex or costimulatory molecules. Analysis of the
      production of interleukin-12 (IL-12), alpha interferon (IFN-alpha), and IFN-gamma
      by the Ad-infected DCs shows no significant differences over noninfected control
      lung DCs. Ad-induced suppression was not due to a deficiency of IL-2 or other DC
      secreted factors and was dependent on viral protein synthesis, as UV irradiation
      of Ad abrogated the suppressive effect. Results suggest that Ad-infected DCs
      induce T cells to be nonresponsive to IL-2 during primary coculture, as the
      addition of IL-2 in secondary cultures recovered T-cell proliferation. In vivo
      studies supported in vitro results showing that Ad infection resulted in lung T
      cells with decreased proliferative ability. This study demonstrates that Ad
      infection induces local immunoincompetence by altering DC-T-cell interactions.

PMID- 16439540
TI  - Modulation of cellular protein trafficking by human immunodeficiency virus type 1
      Nef: role of the acidic residue in the ExxxLL motif.
AB  - The nef gene contributes to the replication of primate lentiviruses by altering
      the trafficking of cellular proteins involved in adaptive immunity (class I and
      II major histocompatibility complex [MHC]) and viral transmission (CD4 and DC
      SIGN). A conserved acidic leucine-based sequence (E(160)xxxLL) within human
      immunodeficiency virus type 1 (HIV-1) Nef binds to the cellular adaptor protein
      (AP) complexes, which mediate protein sorting into endosomal vesicles. The
      leucine residues in this motif are required for the down-regulation of CD4 and
      for the up-regulation of DC-SIGN and the invariant chain of MHC class II, but the
      role of the acidic residue is unclear. Here, substitution of E160 with uncharged
      residues impaired the ability of Nef to up-regulate the expression of the
      invariant chain and DC-SIGN at the cell surface, whereas substitution with a
      basic residue was required for a similar effect on the down-regulation of CD4.
      All substitutions of E160 relieved the Nef-mediated block to transferrin uptake.
      E160 was required for the efficient interaction of Nef with AP-1 and AP-3 and for
      the stabilization of these complexes on endosomal membranes in living cells.
      Systematic mutation of the ExxxLL sequence together with correlation of binding
      and functional data leads to the hypotheses that AP-1 and AP-3 are major
      cofactors for the effect of Nef on the trafficking of transferrin, are less
      important but contribute to the modulation of the invariant chain and DC-SIGN,
      and are least critical for the modulation of CD4. The data suggest that the E160
      residue plays a differential role in the modulation of leucine-dependent Nef
      targets and support a model in which distinct AP complexes are used by Nef to
      modulate different cellular proteins.

PMID- 16439541
TI  - CD4-specific transgenic expression of human cyclin T1 markedly increases human
      immunodeficiency virus type 1 (HIV-1) production by CD4+ T lymphocytes and
      myeloid cells in mice transgenic for a provirus encoding a monocyte-tropic HIV-1
      isolate.
AB  - Human immunodeficiency virus type 1 (HIV-1)-encoded Tat provides transcriptional
      activation critical for efficient HIV-1 replication by interacting with cyclin T1
      and recruiting P-TEFb to efficiently elongate the nascent HIV transcript. Tat
      mediated transcriptional activation in mice is precluded by species-specific
      structural differences that prevent Tat interaction with mouse cyclin T1 and
      severely compromise HIV-1 replication in mouse cells. We investigated whether
      transgenic mice expressing human cyclin T1 under the control of a murine CD4
      promoter/enhancer cassette that directs gene expression to CD4(+) T lymphocytes
      and monocytes/macrophages (hu-cycT1 mice) would display Tat responsiveness in
      their CD4-expressing mouse cells and selectively increase HIV-1 production in
      this cellular population, which is infected primarily in HIV-1-positive
      individuals. To this end, we crossed hu-cycT1 mice with JR-CSF transgenic mice
      carrying the full-length HIV-1(JR-CSF) provirus under the control of the
      endogenous HIV-1 long terminal repeat and demonstrated that human cyclin T1
      expression is sufficient to support Tat-mediated transactivation in primary mouse
      CD4 T lymphocytes and monocytes/macrophages and increases in vitro and in vivo
      HIV-1 production by these stimulated cells. Increased HIV-1 production by CD4(+)
      T lymphocytes was paralleled with their specific depletion in the peripheral
      blood of the JR-CSF/hu-cycT1 mice, which increased over time. In addition,
      increased HIV-1 transgene expression due to human cyclin T1 expression was
      associated with increased lipopolysaccharide-stimulated monocyte chemoattractant
      protein 1 production by JR-CSF mouse monocytes/macrophages in vitro. Therefore,
      the JR-CSF/hu-cycT1 mice should provide an improved mouse system for
      investigating the pathogenesis of various aspects of HIV-1-mediated disease and
      the efficacies of therapeutic interventions.

PMID- 16439542
TI  - Novel Pol II fusion promoter directs human immunodeficiency virus type 1
      inducible coexpression of a short hairpin RNA and protein.
AB  - We demonstrate a novel approach for coexpression of a short hairpin RNA (shRNA)
      with an open reading frame which exploits transcriptional read-through of a
      minimal polyadenylation signal from a Pol II promoter. We first observed
      efficient inducible expression of enhanced green fluorescent protein along with
      an anti-rev shRNA. We took advantage of this observation to test coexpression of
      the transdominant negative mutant (humanized) of human immunodeficiency type 1
      (HIV-1) Rev (huRevM10) along with an anti-rev shRNA via an HIV-1-inducible fusion
      promoter. The coexpression of the shRNA and transdominant protein resulted in
      potent, long-term inhibition of HIV-1 gene expression and suppression of shRNA
      resistant mutants. This dual expression system has broad-based potential for
      other shRNA applications, such as cases where simultaneous knockdown of mutant
      and wild-type transcripts must be accompanied by replacement of the wild-type
      protein.

PMID- 16439543
TI  - Scalable generation of high-titer recombinant adeno-associated virus type 5 in
      insect cells.
AB  - We established a method for production of recombinant adeno-associated virus type
      5 (rAAV5) in insect cells by use of baculovirus expression vectors. One
      baculovirus harbors a transgene between the inverted terminal repeat sequences of
      type 5, and the second expresses Rep78 and Rep52. Interestingly, the replacement
      of type 5 Rep52 with type 1 Rep52 generated four times more rAAV5 particles. We
      replaced the N-terminal portion of type 5 VP1 with the equivalent portion of type
      2 to generate infectious AAV5 particles. The rAAV5 with the modified VP1 required
      alpha2-3 sialic acid for transduction, as revealed by a competition experiment
      with an analog of alpha2-3 sialic acid. rAAV5-GFP/Neo with a 4.4-kb vector genome
      produced in HEK293 cells or Sf9 cells transduced COS cells with similar
      efficiencies. Surprisingly, Sf9-produced humanized Renilla green fluorescent
      protein (hGFP) vector with a 2.4-kb vector genome induced stronger GFP expression
      than the 293-produced one. Transduction of murine skeletal muscles with Sf9
      generated rAAV5 with a 3.4-kb vector genome carrying a human secreted alkaline
      phosphatase (SEAP) expression cassette induced levels of SEAP more than 30 times
      higher than those for 293-produced vector 1 week after injection. Analysis of
      virion DNA revealed that in addition to a 2.4- or 3.4-kb single-stranded vector
      genome, Sf9-rAAV5 had more-abundant forms of approximately 4.7 kb, which appeared
      to correspond to the monomer duplex form of hGFP vector or truncated monomer
      duplex SEAP vector DNA. These results indicated that rAAV5 can be generated in
      insect cells, although the difference in incorporated virion DNA may induce
      different expression patterns of the transgene.

PMID- 16439544
TI  - Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its
      role in the replication cycle of human immunodeficiency virus.
AB  - After identifying the interaction between the transcriptional coactivator lens
      epithelium-derived growth factor (LEDGF/p75) and the human immunodeficiency virus
      type 1 (HIV-1) integrase (IN), we have now investigated the role of LEDGF/p75
      during HIV replication. Transient small interfering RNA-mediated knockdown of
      LEDGF/p75 in HeLaP4 cells resulted in a three- to fivefold inhibition of HIV-1
      (strain NL4.3) replication. Quantitative PCR was used to pinpoint the replication
      block to the integration step. Next, polyclonal and monoclonal HeLaP4-derived
      cell lines were selected with a stable knockdown of LEDGF/p75 mediated by a
      lentiviral vector (lentivector) encoding a short hairpin RNA (shRNA) targeting
      this protein. Cell lines stably transduced with a lentivector encoding an
      unrelated hairpin or a double-mismatch hairpin served as controls. Again, a two-
      to fourfold reduction of HIV-1 replication was observed. The extent of LEDGF/p75
      knockdown closely correlated with the reduction of HIV-1 replication. After the
      back-complementation of LEDGF/p75 in the poly- and monoclonal knockdown cell
      lines using an shRNA-resistant expression plasmid, viral replication was restored
      to nearly wild-type levels. The Q168A mutation in integrase has been shown to
      interfere with the interaction with LEDGF/p75 without reducing the enzymatic
      activity. Transduction by HIV-1-derived lentivectors carrying the Q168A IN mutant
      was severely hampered, pointing again to a requirement for LEDGF/p75. Altogether,
      our data validate LEDGF/p75 as an important cellular cofactor for HIV integration
      and as a potential target for antiviral drug development.

PMID- 16439545
TI  - The Arg279Gln [corrected] substitution in the adenovirus type 11p (Ad11p) fiber
      knob abolishes EDTA-resistant binding to A549 and CHO-CD46 cells, converting the
      phenotype to that of Ad7p.
AB  - The major determinant of adenovirus (Ad) attachment to host cells is the C
      terminal knob domain of the trimeric fiber protein. Ad type 11p (Ad11p; species
      B2) in contrast to Ad7p (species B1) utilizes at least two different cellular
      attachment receptors, designated sBAR (species B adenovirus receptor) and sB2AR
      (species B2 adenovirus receptor). CD46 has recently been identified as one of the
      Ad11p attachment receptors. However, CD46 did not seem to constitute a functional
      receptor for Ad7p. Although Ad7p shares high knob amino acid identity with Ad11p,
      Ad7p is deficient in binding to both sB2AR and CD46. To determine what regions of
      the Ad11p fiber knob are necessary for sB2AR-CD46 interaction, we constructed
      recombinant fiber knobs (rFK) with Ad11p/Ad7p chimeras and Ad11p sequences having
      a single amino acid substitution from Ad7p. Binding of the constructs to A549 and
      CHO-CD46 BC1 isoform-expressing cells was analyzed by flow cytometry. Our results
      indicate that an Arg279Gln [corrected] substitution is sufficient to convert the
      Ad11p receptor-interaction phenotype to that of Ad7p and abolish sB2AR and CD46
      interaction. Also a Glu279Arg substitution in Ad7p rFKs increases CD46 binding.
      Thus, the lateral HI loop of the Ad11p fiber knob seems to be the key determinant
      for Ad11p sB2AR-CD46 interaction. This result is comparable to another non
      coxsackie-adenovirus receptor binding Ad (Ad37p), where substitution of one amino
      acid abolishes virus-cell interaction. In conjunction with previous results, our
      findings also strongly suggest that sB2AR is equivalent to CD46.

PMID- 16439546
TI  - The leader proteinase of foot-and-mouth disease virus inhibits the induction of
      beta interferon mRNA and blocks the host innate immune response.
AB  - We have previously shown that the leader proteinase (L(pro)) of foot-and-mouth
      disease virus (FMDV) blocks cap-dependent mRNA translation and that a genetically
      engineered FMDV lacking the leader proteinase coding region (A12-LLV2) is
      attenuated in cell culture and susceptible animals. The attenuated phenotype
      apparently is a consequence of the inability of A12-LLV2 to block the expression
      of type I interferon (IFN-alpha/beta) protein, resulting in IFN-induced
      inhibition of FMDV replication. Here we show that in addition to preventing IFN
      alpha/beta protein synthesis, L(pro) reduces the level of immediate-early
      induction of IFN-beta mRNA and IFN-stimulated gene products such as double
      stranded RNA-dependent protein kinase R (PKR), 2',5'-oligoadenylate synthetase,
      and Mx1 mRNAs in swine cells. Down-regulation of cellular PKR by RNA interference
      did not affect wild-type virus yield but resulted in a higher yield of A12-LLV2,
      indicating a direct role of PKR in controlling FMDV replication in the natural
      host. The observation that L(pro) controls the transcription of genes involved in
      innate immunity reveals a novel role of this protein in antagonizing the cellular
      response to viral infection.

PMID- 16439547
TI  - Core protein of pestiviruses is processed at the C terminus by signal peptide
      peptidase.
AB  - The core protein of pestiviruses is released from the polyprotein by viral and
      cellular proteinases. Here we report on an additional intramembrane proteolytic
      step that generates the C terminus of the core protein. C-terminal processing of
      the core protein of classical swine fever virus (CSFV) was blocked by the
      inhibitor (Z-LL)(2)-ketone, which is specific for signal peptide peptidase (SPP).
      The same effect was obtained by overexpression of the dominant-negative SPP
      D(265)A mutant. The presence of (Z-LL)(2)-ketone reduced the viability of CSFV
      almost 100-fold in a concentration-dependent manner. Reduction of virus viability
      was also observed in infection experiments using a cell line that inducibly
      expressed SPP D(265)A. The position of SPP cleavage was determined by C-terminal
      sequencing of core protein purified from virions. The C terminus of CSFV core
      protein is alanine(255) and is located in the hydrophobic center of the signal
      peptide. The intramembrane generation of the C terminus of the CSFV core protein
      is almost identical to the processing scheme of the core protein of hepatitis C
      viruses.

PMID- 16439548
TI  - Insights into gene expression changes impacting B-cell transformation: cross
      species microarray analysis of bovine leukemia virus tax-responsive genes in
      ovine B cells.
AB  - Large-animal models for leukemia have the potential to aid in the understanding
      of networks that contribute to oncogenesis. Infection of cattle and sheep with
      bovine leukemia virus (BLV), a complex retrovirus related to human T-cell
      leukemia virus type 1 (HTLV-1), is associated with the development of B-cell
      leukemia. Whereas the natural disease in cattle is characterized by a low tumor
      incidence, experimental infection of sheep leads to overt leukemia in the
      majority of infected animals, providing a model for studying the pathogenesis
      associated with BLV and HTLV-1. Tax(BLV), the major oncoprotein, initiates a
      cascade of events leading toward malignancy, although the basis of transformation
      is not fully understood. We have taken a cross-species ovine-to-human microarray
      approach to identify Tax(BLV)-responsive transcriptional changes in two sets of
      cultured ovine B cells following retroviral vector-mediated delivery of Tax(BLV).
      Using cDNA-spotted microarrays comprising 10,336 human genes/expressed sequence
      tags, we identified a cohort of differentially expressed genes, including genes
      related to apoptosis, DNA transcription, and repair; proto-oncogenes; cell cycle
      regulators; transcription factors; small Rho GTPases/GTPase-binding proteins; and
      previously reported Tax(HTLV-1)-responsive genes. Interestingly, genes known to
      be associated with human neoplasia, especially B-cell malignancies, were
      extensively represented. Others were novel or unexpected. The results suggest
      that Tax(BLV) deregulates a broad network of interrelated pathways rather than a
      single B-lineage-specific regulatory process. Although cross-species approaches
      do not permit a comprehensive analysis of gene expression patterns, they can
      provide initial clues for the functional roles of genes that participate in B
      cell transformation and pinpoint molecular targets not identified using other
      methods in animal models.

PMID- 16439549
TI  - Human immunodeficiency virus type 1 incorporated with fusion proteins consisting
      of integrase and the designed polydactyl zinc finger protein E2C can bias
      integration of viral DNA into a predetermined chromosomal region in human cells.
AB  - In vitro studies using fusion proteins consisting of human immunodeficiency virus
      type 1 integrase (IN) and a synthetic polydactyl zinc finger protein E2C, a
      sequence-specific DNA-binding protein, showed that integration of retroviral DNA
      can be biased towards a contiguous 18-bp E2C-recognition site. To determine
      whether the fusion protein strategy can achieve site-specific integration in
      vivo, viruses were prepared by cotransfection and various IN-E2C fusion proteins
      were packaged in trans into virions. The resulting viruses incorporated with the
      IN-E2C fusion proteins were functional and capable of performing integration at a
      level ranging from 1 to 24% of that of viruses containing wild-type (WT) IN. Two
      of the more infectious viruses, which contained E2C fused to either the N
      (E2C/IN) or to the C (IN/E2C) terminus of IN, were tested for their ability to
      direct integration into a unique E2C-binding site present within the 5'
      untranslated region of erbB-2 gene on human chromosome 17. The copy number of
      proviral DNA was measured using a quantitative real-time nested-PCR assay, and
      the specificity of directed integration was determined by comparing the number of
      proviruses within the vicinity of the E2C-binding site to that in the whole
      genome. Viruses containing IN/E2C fusion proteins had sevenfold higher preference
      for integrating near the E2C-binding site than those viruses containing WT IN,
      whereas viruses containing E2C/IN had 10-fold higher preference. The results
      indicated that the IN-E2C fusion protein strategy is capable of directing
      integration of retroviral DNA into a predetermined chromosomal region in the
      human genome.

PMID- 16439550
TI  - Involvement of multiple epitope-specific cytotoxic T-lymphocyte responses in
      vaccine-based control of simian immunodeficiency virus replication in rhesus
      macaques.
AB  - Cytotoxic T-lymphocyte (CTL) responses are crucial for the control of
      immunodeficiency virus replication. Possible involvement of a dominant single
      epitope-specific CTL in control of viral replication has recently been indicated
      in preclinical AIDS vaccine trials, but it has remained unclear if multiple
      epitope-specific CTLs can be involved in the vaccine-based control. Here, by
      following up five rhesus macaques that showed vaccine-based control of primary
      replication of a simian immunodeficiency virus, SIVmac239, we present evidence
      indicating involvement of multiple epitope-specific CTL responses in this
      control. Three macaques maintained control for more than 2 years without
      additional mutations in the provirus. However, in the other two that shared a
      major histocompatibility complex haplotype, viral mutations were accumulated in a
      similar order, leading to viral evasion from three epitope-specific CTL responses
      with viral fitness costs. Accumulation of these multiple escape mutations
      resulted in the reappearance of plasma viremia around week 60 after challenge.
      Our results implicate multiple epitope-specific CTL responses in control of
      immunodeficiency virus replication and furthermore suggest that sequential
      accumulation of multiple CTL escape mutations, if allowed, can result in viral
      evasion from this control.

PMID- 16439552
TI  - Dependence of the encapsidation function of the adenovirus L1 52/55-kilodalton
      protein on its ability to bind the packaging sequence.
AB  - The adenovirus IVa2 and L1 52/55-kDa proteins are involved in the assembly of new
      virus particles. Both proteins bind to the packaging sequence of the viral
      chromosome, and the lack of expression of either protein results in no virus
      progeny: the absence of the L1 52/55-kDa protein leads to formation of only empty
      capsids, and the absence of the IVa2 protein results in no capsid assembly.
      Furthermore, the IVa2 and L1 52/55-kDa proteins interact with each other during
      adenovirus infection. However, what is not yet clear is when and how this
      interaction occurs during the course of the viral infection. We defined the
      domains of the L1 52/55-kDa protein required for interaction with the IVa2
      protein, DNA binding, and virus replication by constructing L1 52/55-kDa protein
      truncations. We found that the N-terminal 173 amino acids of the L1 52/55-kDa
      protein are essential for interaction with the IVa2 protein. However, for both
      DNA binding and complementation of the pm8001 mutant virus, which does not
      express the L1 52/55-kDa protein, the amino-terminal 331 amino acids of the L1
      52/55-kDa protein are necessary. These results suggest that the production of
      infectious virus particles depends on the ability of the L1 52/55-kDa protein to
      bind to DNA.

PMID- 16439551
TI  - Protection of mice and poultry from lethal H5N1 avian influenza virus through
      adenovirus-based immunization.
AB  - The recent emergence of highly pathogenic avian influenza virus (HPAI) strains in
      poultry and their subsequent transmission to humans in Southeast Asia have raised
      concerns about the potential pandemic spread of lethal disease. In this paper we
      describe the development and testing of an adenovirus-based influenza A virus
      vaccine directed against the hemagglutinin (HA) protein of the
      A/Vietnam/1203/2004 (H5N1) (VN/1203/04) strain isolated during the lethal human
      outbreak in Vietnam from 2003 to 2005. We expressed different portions of HA from
      a recombinant replication-incompetent adenoviral vector, achieving vaccine
      production within 36 days of acquiring the virus sequence. BALB/c mice were
      immunized with a prime-boost vaccine and exposed to a lethal intranasal dose of
      VN/1203/04 H5N1 virus 70 days later. Vaccination induced both HA-specific
      antibodies and cellular immunity likely to provide heterotypic immunity. Mice
      vaccinated with full-length HA were fully protected from challenge with
      VN/1203/04. We next evaluated the efficacy of adenovirus-based vaccination in
      domestic chickens, given the critical role of fowl species in the spread of HPAI
      worldwide. A single subcutaneous immunization completely protected chickens from
      an intranasal challenge 21 days later with VN/1203/04, which proved lethal to all
      control-vaccinated chickens within 2 days. These data indicate that the rapid
      production and subsequent administration of recombinant adenovirus-based vaccines
      to both birds and high-risk individuals in the face of an outbreak may serve to
      control the pandemic spread of lethal avian influenza.

PMID- 16439553
TI  - Antibody prophylaxis and therapy against Nipah virus infection in hamsters.
AB  - Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic
      infection in which the reservoir, the fruit bat, may pass the infection to pigs
      and eventually to humans. In humans, the infection leads to encephalitis with >40
      to 70% mortality. We have previously shown that polyclonal antibody directed to
      either one of two glycoproteins, G (attachment protein) or F (fusion protein),
      can protect hamsters from a lethal infection. In the present study, we have
      developed monoclonal antibodies (MAbs) to both glycoproteins and assessed their
      ability to protect animals against lethal NiV infection. We show that as little
      as 1.2 mug of an anti-G MAb protected animals, whereas more than 1.8 mug of anti
      F MAb was required to completely protect the hamsters. High levels of either anti
      G or anti-F MAbs gave a sterilizing immunity, whereas lower levels could protect
      against a fatal infection but resulted in an increase in anti-NiV antibodies
      starting 18 days after the viral challenge. Using reverse transcriptase PCR, the
      presence of NiV in the different organs could not be observed in MAb-protected
      animals. When the MAbs were given after infection, partial protection (50%) was
      observed with the anti-G MAbs when the animals were inoculated up to 24 h after
      infection, but administration of the anti-F MAbs protected some animals (25 to
      50%) inoculated later during the infection. Our studies suggest that
      immunotherapy could be used for people who are exposed to NiV infections.

PMID- 16439554
TI  - Nuclear import of Epstein-Barr virus nuclear antigen 1 mediated by NPI-1
      (Importin alpha5) is up- and down-regulated by phosphorylation of the nuclear
      localization signal for which Lys379 and Arg380 are essential.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is essential for replication
      of episomal EBV DNAs and maintenance of latency. Multifunctional EBNA-1 is
      phosphorylated, but the significance of EBNA-1 phosphorylation is not known.
      Here, we examined the effects on nuclear translocation of Ser phosphorylation of
      the EBNA-1 nuclear localization signal (NLS) sequence, 379Lys-Arg-Pro-Arg-Ser-Pro
      Ser-Ser386. We found that Lys379Ala and Arg380Ala substitutions greatly reduced
      nuclear transport and steady-state levels of green fluorescent protein (GFP)
      EBNA1, whereas Pro381Ala, Arg382Ala, Pro384Ala, and Glu378Ala substitutions did
      not. Microinjection of modified EBNA-1 NLS peptide-inserted proteins and NLS
      peptides cross-linked to bovine serum albumin (BSA) showed that Ala substitution
      for three NLS Ser residues reduced the efficiency of nuclear import. Similar
      microinjection analyses demonstrated that phosphorylation of Ser385 accelerated
      the rate of nuclear import, but phosphorylation of Ser383 and Ser386 reduced it.
      However, transfection analyses of GFP-EBNA1 mutants with the Ser-to-Ala
      substitution causing reduced nuclear import efficiency did not result in a
      decrease in the nuclear accumulation level of EBNA-1. The results suggest dynamic
      nuclear transport control of phosphorylated EBNA-1 proteins, although the nuclear
      localization level of EBNA-1 that binds to cellular chromosomes and chromatin
      seems unchanged. The karyopherin alpha NPI-1 (importin alpha5), a nuclear import
      adaptor, bound more strongly to Ser385-phosphorylated NLS than to any other
      phosphorylated or nonphosphorylated forms. Rch1 (importin alpha1) bound only
      weakly and Qip1 (importin alpha3) did not bind to the Ser385-phosphorylated NLS.
      These findings suggest that the amino-terminal 379Lys-Arg380 is essential for the
      EBNA-1 NLS and that Ser385 phosphorylation up-regulates nuclear transport
      efficiency of EBNA-1 by increasing its binding affinity to NPI-1, while
      phosphorylation of Ser386 and Ser383 down-regulates it.

PMID- 16439555
TI  - Human immunodeficiency virus fusion to dendritic cells declines as cells mature.
AB  - The maturation of dendritic cells (DCs) is associated with a diminished ability
      to support human immunodeficiency virus (HIV) replication; however, the precise
      step in the HIV life cycle impaired by DC maturation remains uncertain. Using an
      HIV virion-based fusion assay, we now show that HIV fusion to monocyte-derived
      DCs (MDDCs) both decreases and kinetically slows when DCs are induced to mature
      with poly(I:C) and tumor necrosis factor alpha. Specifically, laboratory-adapted
      CCR5-tropic 81A virions fused with markedly lower efficiency to mature MDDCs than
      immature DCs. In contrast, fusion of NL4-3, the isogenic CXCR4-tropic counterpart
      of 81A, was low in both immature and mature MDDCs. Fusion mediated by primary HIV
      envelopes, including seven CCR5- and four CXCR4-tropic envelopes, also decreased
      with DC maturation. The kinetics of virion fusion were also altered by both the
      state of DC maturation and the coreceptor utilized. Fusion of 81A and NL4-3
      virions was delayed in mature compared to immature MDDCs, and NL4-3 fused more
      slowly than 81A in both mature and immature MDDCs. Surprisingly, primary
      envelopes with CXCR4 tropism mediated fusion to immature MDDCs with efficiencies
      similar to those of primary CCR5-tropic envelopes. This result contrasted with
      the marked preferential fusion of the laboratory-adapted 81A over NL4-3 in
      immature MDDCs and in ex vivo Langerhans cells, indicating that these laboratory
      adapted HIV strains do not fully recapitulate all of the properties of primary
      HIV isolates. In conclusion, our results demonstrate that the defect in HIV
      replication observed in mature MDDCs stems at least in part from a decline in
      viral fusion.

PMID- 16439556
TI  - Genetic identification of adenovirus type 5 genes that influence viral spread.
AB  - The mechanisms that control cell-to-cell spread of human adenoviruses (Ad) are
      not well understood. Two early viral proteins, E1B-19K and E3-ADP, appear to have
      opposing effects since viral mutants that are individually deficient in E1B-19K
      produce large plaques (G. Chinnadurai, Cell 33:759-766, 1983), while mutants
      deficient in E3-ADP produce small plaques (A. E. Tollefson et al., J. Virol.
      70:2296-2306, 1996) on infected cell monolayers. We have used a genetic strategy
      to identify different viral genes that influence adenovirus type 5 (Ad5) spread
      in an epithelial cancer cell line. An Ad5 mutant (dl327; lacking most of the E3
      region) with the restricted-spread (small-plaque) phenotype was randomly
      mutagenized with UV, and 27 large-plaque (lp) mutants were isolated. A
      combination of analyses of viral proteins and genomic DNA sequences have
      indicated that 23 mutants contained lesions in the E1B region affecting either
      19K or both 19K and 55K proteins. Four other lp mutants contained lesions in
      early regions E1A and E4, in the early L1 region that codes for the i-leader
      protein, and in late regions that code for the viral structural proteins, penton
      base, and fiber. Our results suggest that the requirement of E3-ADP for Ad spread
      could be readily compensated for by abrogation of the functions of E1B-19K and
      provide genetic evidence that these two viral proteins influence viral spread in
      opposing manners. In addition to E1B and E3 proteins, other early and late
      proteins that regulate viral replication and infectivity also influence lateral
      viral spread. Our studies have identified novel mutations that could be exploited
      in designing efficient oncolytic Ad vectors.

PMID- 16439557
TI  - Dual wavelength imaging allows analysis of membrane fusion of influenza virus
      inside cells.
AB  - Influenza virus hemagglutinin (HA) is a determinant of virus infectivity.
      Therefore, it is important to determine whether HA of a new influenza virus,
      which can potentially cause pandemics, is functional against human cells. The
      novel imaging technique reported here allows rapid analysis of HA function by
      visualizing viral fusion inside cells. This imaging was designed to detect fusion
      changing the spectrum of the fluorescence-labeled virus. Using this imaging, we
      detected the fusion between a virus and a very small endosome that could not be
      detected previously, indicating that the imaging allows highly sensitive
      detection of viral fusion.

PMID- 16439558
TI  - Reovirus induces and benefits from an integrated cellular stress response.
AB  - Following infection with most reovirus strains, viral protein synthesis is
      robust, even when cellular translation is inhibited. To gain further insight into
      pathways that regulate translation in reovirus-infected cells, we performed a
      comparative microarray analysis of cellular gene expression following infection
      with two strains of reovirus that inhibit host translation (clone 8 and clone 87)
      and one strain that does not (Dearing). Infection with clone 8 and clone 87
      significantly increased the expression of cellular genes characteristic of stress
      responses, including the integrated stress response. Infection with these same
      strains decreased transcript and protein levels of P58(IPK), the cellular
      inhibitor of the eukaryotic initiation factor 2alpha (eIF2alpha) kinases PKR and
      PERK. Since infection with host shutoff-inducing strains of reovirus impacted
      cellular pathways that control eIF2alpha phosphorylation and unphosphorylated
      eIF2alpha is required for translation initiation, we examined reovirus
      replication in a variety of cell lines with mutations that impact eIF2alpha
      phosphorylation. Our results revealed that reovirus replication is more efficient
      in the presence of eIF2alpha kinases and phosphorylatable eIF2alpha. When
      eIF2alpha is phosphorylated, it promotes the synthesis of ATF4, a transcription
      factor that controls cellular recovery from stress. We found that the presence of
      this transcription factor increased reovirus yields 10- to 100-fold. eIF2alpha
      phosphorylation also led to the formation of stress granules in reovirus-infected
      cells. Based on these results, we hypothesize that eIF2alpha phosphorylation
      facilitates reovirus replication in two ways-first, by inducing ATF4 synthesis,
      and second, by creating an environment that places abundant reovirus transcripts
      at a competitive advantage for limited translational components.

PMID- 16439559
TI  - Cytotoxic T-lymphocyte epitope vaccination protects against human metapneumovirus
      infection and disease in mice.
AB  - Human metapneumovirus (hMPV) has emerged as an important human respiratory
      pathogen causing upper and lower respiratory tract infections in young children
      and older adults. In addition, hMPV infection is associated with asthma
      exacerbation in young children. Recent epidemiological evidence indicates that
      hMPV may cocirculate with human respiratory syncytial virus (hRSV) and mediate
      clinical disease similar to that seen with hRSV. Therefore, a vaccine for hMPV is
      highly desirable. In the present study, we used predictive bioinformatics,
      peptide immunization, and functional T-cell assays to define hMPV cytotoxic T
      lymphocyte (CTL) epitopes recognized by mouse T cells restricted through several
      major histocompatibility complex class I alleles, including HLA-A*0201. We
      demonstrate that peptide immunization with hMPV CTL epitopes reduces viral load
      and immunopathology in the lungs of hMPV-challenged mice and enhances the
      expression of Th1-type cytokines (gamma interferon and interleukin-12 [IL-12]) in
      lungs and regional lymph nodes. In addition, we show that levels of Th2-type
      cytokines (IL-10 and IL-4) are significantly lower in hMPV CTL epitope-vaccinated
      mice challenged with hMPV. These results demonstrate for the first time the
      efficacy of an hMPV CTL epitope vaccine in the control of hMPV infection in a
      murine model.

PMID- 16439560
TI  - cdc2/cyclin B1-dependent phosphorylation of EBNA2 at Ser243 regulates its
      function in mitosis.
AB  - Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) transactivates EBV genes in
      latently infected B cells. We have shown that mitotic hyperphosphorylation of
      EBNA2 suppresses its ability to transactivate the latent membrane protein 1
      (LMP1) promoter. In this follow-up study, we identify EBNA2 Ser243 as a
      phosphorylation site for mitotic cdc2/cyclin B1 kinase. Mutation at Ser243, which
      mimics constitutive phosphorylation of the protein, decreases endogenous levels
      of both LMP1 and EBNA2. Moreover, mutation at Ser243 reduces the ability of EBNA2
      to transactivate Cp, the promoter for all six EBV EBNA genes. Our data implicate
      EBNA2 Ser243 as a cdc2/cyclin B1 site of phosphorylation important for EBNA2's
      cotranscriptional function in mitosis.

PMID- 16439561
TI  - Arsenic counteracts human immunodeficiency virus type 1 restriction by various
      TRIM5 orthologues in a cell type-dependent manner.
AB  - Arsenic trioxide (As(2)O(3)) increased human immunodeficiency virus type 1 (HIV
      1) infectivity when particular Homo sapiens and Cercopithecus aethiops cell lines
      were used as targets. Knockdown of human TRIM5alpha by RNA interference
      eliminated the As(2)O(3) effect, demonstrating that the drug acts by modulating
      the activity of this retroviral restriction factor. In contrast, HIV-1
      infectivity in target cell lines from other primate species (Cercopithecus
      tantalus, Macaca mulatta, and Aotus trivirgatus) was not increased by As(2)O(3),
      despite the potent TRIM5-dependent HIV-1 restriction activity that these cells
      exhibit. To determine if As(2)O(3) responsiveness is characteristic of particular
      TRIM5 orthologues and not others, TRIM5 cDNAs from these five primate species
      were transduced into cat fibroblasts, which lack endogenous HIV-1 restriction
      activity and, therefore, responsiveness to As(2)O(3). In this context, the HIV-1
      restriction activity conferred by all TRIM5 orthologues was largely eliminated by
      As(2)O(3). The effect of As(2)O(3) on HIV-1 restriction is thus shared by
      different TRIM5 orthologues but dependent on factors specific to the cell line in
      which TRIM5 is expressed.

PMID- 16439562
TI  - Identification of spliced gammaherpesvirus 68 LANA and v-cyclin transcripts and
      analysis of their expression in vivo during latent infection.
AB  - Regulation of orf73 (LANA) gene expression is critical to the establishment and
      maintenance of latency following infection by members of the gamma-2 herpesvirus
      (rhadinovirus) family. Previous studies of murine gammaherpesvirus 68 (gammaHV68)
      have demonstrated that loss of LANA function results in a complete failure to
      establish virus latency in the spleens of laboratory mice. Here we report the
      characterization of alternatively spliced LANA and v-cyclin (orf72) transcripts
      encoded by gammaHV68. Similar to other rhadinoviruses, alternative splicing,
      coupled with alternative 3' processing, of a ca. 16-kb transcriptional unit can
      lead to expression of either LANA or v-cyclin during gammaHV68 infection. Spliced
      LANA and v-cyclin transcripts were initially identified from an analysis of the
      gammaHV68 latently infected B-cell lymphoma cell line S11E, but were also
      detected during lytic infection of NIH 3T12 fibroblasts. 5' Random amplification
      of cDNA ends (RACE) analyses identified two distinct promoters, p1 and p2, that
      drive expression of spliced LANA transcripts. Analysis of p1 and p2, using
      transiently transfected reporter constructs, mapped the minimal sequences
      required for promoter activity and demonstrated that both promoters are active in
      the absence of any viral antigens. Analysis of spliced LANA and v-cyclin
      transcripts in spleens recovered from latently infected mice at days 16 and 42
      postinfection revealed that spliced v-cyclin transcripts can only be detected
      sporadically, suggesting that these may be associated with cells reactivating
      from latency. In contrast, spliced LANA transcripts were detected in ca. 1 in
      4,000 splenocytes harvested at day 16 postinfection. Notably, based on the
      frequency of viral genome-positive splenocytes at day 16 postinfection (ca. 1 in
      200), only 5 to 10% of viral genome-positive splenocytes express LANA. The
      failure of the majority of infected splenocytes at day 16 postinfection to
      express LANA may contribute to the contraction in the frequency of latently
      infected splenocytes as chronic infection is established, due to failure to
      maintain the viral episome in proliferating B cells.

PMID- 16439563
TI  - Deacetylation of the herpes simplex virus type 1 latency-associated transcript
      (LAT) enhancer and a decrease in LAT abundance precede an increase in ICP0
      transcriptional permissiveness at early times postexplant.
AB  - Only the latency-associated transcript (LAT) of the herpes simplex virus type 1
      (HSV-1) genome is transcribed during latency, while the lytic genes are
      suppressed, possibly by LAT antisense mechanisms and/or chromatin modifications.
      In the present study, latently infected dorsal root ganglia were explanted to
      assess both relative levels of LAT and histone H3 (K9, K14) acetylation of the
      LAT locus and ICP0 promoter at early times postexplant. We observed that a
      decrease in both LAT enhancer histone H3 (K9, K14) acetylation and LAT RNA
      abundance occurs prior to an increase in acetylation, or transcriptional
      permissiveness, at the ICP0 promoter.

PMID- 16439565
TI  - Perfusion MR imaging with FAIR true FISP spin labeling in patients with and
      without renal artery stenosis: initial experience.
AB  - The purpose of this study was to prospectively evaluate an arterial spin-labeling
      technique, flow-sensitive alternating inversion-recovery (FAIR) true fast imaging
      with steady-state precession (FISP), for noninvasive quantification of renal
      perfusion in patients without a history of renal artery stenosis (RAS) and in
      patients with proved RAS. The study was approved by the local ethics committee,
      and all participants provided written informed consent. Six patients with
      hypertension but no history of renal artery disease and 12 patients with RAS
      underwent FAIR true FISP magnetic resonance (MR) imaging in a whole-body 1.5-T
      unit. RAS grade and scintigraphic perfusion data served as the reference
      standards. On the FAIR true FISP perfusion images, severe RAS (>70% luminal
      narrowing) could be clearly distinguished from no or mild RAS and moderate RAS (<
      or =70% luminal narrowing) (P < .005). Significant correlations between FAIR
      perfusion data and stenosis grade (r = -0.76) and between FAIR and single photon
      emission computed tomographic perfusion values (r = 0.83) were observed. FAIR
      true FISP was found to be suitable for quantitative perfusion imaging of the
      kidneys in patients with RAS.

PMID- 16439564
TI  - APOBEC3F and APOBEC3G mRNA levels do not correlate with human immunodeficiency
      virus type 1 plasma viremia or CD4+ T-cell count.
AB  - APOBEC3F and APOBEC3G (hA3F and hA3G) are part of an innate mechanism of
      antiretroviral defense. The human immunodeficiency virus type 1 (HIV-1) accessory
      protein Vif targets both proteins for proteasomal degradation. Using mRNA from
      peripheral blood mononuclear cells of 92 HIV-infected subjects not taking
      antiretroviral therapy and 19 HIV-uninfected controls, we found that hA3F (P <
      0.001) and hA3G (P = 0.016) mRNA levels were lower in HIV-infected subjects and
      were positively correlated with one another (P = 0.003). However, we found no
      correlation in the abundance of either hA3F or hA3G mRNA with either viral load
      or CD4 counts in HIV-infected subjects.

PMID- 16439566
TI  - Pancreatic cysts 3 cm or smaller: how aggressive should treatment be?
AB  - PURPOSE: To retrospectively determine the frequency of malignancy in small (< or
      =3 cm) pancreatic cysts, to evaluate whether cyst morphologic features can help
      predict the presence of malignancy, and to determine the natural history of small
      pancreatic cysts at follow-up imaging. MATERIALS AND METHODS: Institutional
      review board approval was obtained; informed patient consent was not required. By
      means of a computerized search, 510 patients with pancreatic cysts that had been
      detected at computed tomography (CT) or magnetic resonance (MR) imaging were
      identified. Cysts that were 3 cm or smaller at surgery or endoscopic
      ultrasonography (US)-guided cyst fluid aspiration and biopsy were included.
      Eighty-six patients-31 men and 55 women aged 24-89 years-fulfilled the criteria.
      Patients underwent surgery or were monitored with endoscopic US-guided cyst fluid
      analysis, cytologic analysis, and follow-up imaging. Imaging findings were
      compared with surgical and pathology records and with endoscopic US features.
      Positive predictive values (PPVs) for benignity and malignancy were calculated on
      the basis of cyst size and absence or presence of septa in the cysts. RESULTS:
      Forty-eight patients underwent surgery, and 38 were treated nonsurgically.
      Seventy-five patients had benign cysts; eight, borderline (malignant) neoplasms;
      and three, carcinoma in situ lesions. The PPV of small pancreatic cysts for
      prediction of benignity was 87% (75 of 86 patients). Thirty-six patients had
      unilocular cysts (35 with benign lesions, one with borderline neoplasm). The PPV
      of unilocular cysts for prediction of benignity was 97% (35 of 36 patients).
      Fifty patients had septated cysts; seven of these patients had borderline
      neoplasms, and three had carcinoma in situ lesions. For prediction of malignancy
      in small cysts, the PPV of septa was 20% (10 of 50 patients), which was
      significantly higher than the 3% (one of 36 patients) PPV of unilocular cysts (P
      = .042). No significant changes in cyst morphologic features were seen in
      patients who were followed up with imaging for a mean period of 21.8 months.
      CONCLUSION: The majority (n = 75) of small pancreatic cysts were benign. Thirty
      six cysts were unilocular, and virtually all of these (n = 35) were benign. The
      presence of septa was associated with borderline or in situ malignancy in 20% (10
      of 50) of cases.

PMID- 16439567
TI  - Evaluation of living liver donors with an all-inclusive 3D multi-detector row CT
      protocol.
AB  - PURPOSE: To prospectively assess parenchymal, vascular, and biliary anatomy of
      potential living liver donors with an all-inclusive multi-detector row computed
      tomographic (CT) approach. MATERIALS AND METHODS: A total of 250 potential living
      liver donors (112 women, 138 men; mean age, 37 years) underwent three-phase, dual
      enhancement multi-detector row CT to delineate biliary, vascular, and parenchymal
      morphology according to an institutional review board-approved protocol. Informed
      consent was obtained from all subjects. For display of the biliary system, the
      first CT image set was collected after the infusion of a biliary contrast agent.
      CT angiography was subsequently performed, after automated injection of a
      conventional iodinated contrast agent, to display the arterial and portal-hepatic
      venous systems. All data sets were reconstructed in 1-mm sections. Data analysis
      was based on source images, multiplanar reconstructions, and three-dimensional
      postprocessing images; was performed in consensus by two radiologists; and was
      focused on the detection of biliary and vascular variants, exclusion of focal
      liver lesions, and determination of hepatic volumes. Preoperative findings were
      correlated with intraoperative findings (available in 62 subjects). RESULTS:
      Technical failures were experienced in 10 of 250 examinations. Twenty-seven
      subjects had moderate adverse reactions related to the biliary contrast agent.
      Benign hepatic lesions were detected in 61 candidates; one candidate had a renal
      cell carcinoma. Underlying biliary and vascular anatomy was displayed at least to
      the second intrahepatic branch in all but seven patients. Detected anatomic
      variants involved the biliary (38.8%), arterial (40.0%), portal venous (21.4%),
      and hepatic venous (43.5%) systems. Correlation with intraoperative findings was
      excellent. Some biliary (n = 4), arterial (n = 5), portal venous (n = 1), and
      hepatic venous (n = 6) variants were missed or misinterpreted at initial reading
      of preoperative data; however, variants could be retrospectively depicted in all
      but one biliary case and one hepatic venous case. CONCLUSION: The outlined three
      phase, dual-enhancement multi-detector row CT protocol represents an all
      inclusive approach to evaluate potential living liver donors in a single
      diagnostic step.

PMID- 16439568
TI  - Clinician's commentary.

PMID- 16439569
TI  - Functional MR imaging: comparison of BOLD signal intensity changes in fetal
      organs with fetal and maternal oxyhemoglobin saturation during hypoxia in sheep.
AB  - PURPOSE: To compare relative changes in blood oxygen level-dependent (BOLD)
      signal intensity in the fetal brain, liver, heart, lungs, and cotyledon with
      maternal and fetal blood oxygenation during maternal hypoxia in sheep. MATERIALS
      AND METHODS: All experimental protocols were reviewed and approved by local
      authorities on animal protection. Six anesthetized ewes carrying singleton
      fetuses underwent magnetic resonance (MR) imaging with rapid single-shot echo
      planar imaging BOLD sequence. BOLD imaging of the fetal brain, lungs, liver,
      heart, and cotyledon was performed during a control phase (ie, normoxia) and a
      hypoxic phase. Maternal oxyhemoglobin saturation was recorded continuously with
      pulse oximetry. Fetal blood samples were obtained with a carotid catheter at each
      phase. Regions of interest were placed in fetal organs. Normalized BOLD signal
      intensity was calculated with mean values of control and hypoxic plateaus. BOLD
      signal intensity was correlated with maternal oxyhemoglobin saturation and fetal
      oxyhemoglobin saturation; linear regression analysis was performed. RESULTS:
      Control maternal and fetal oxyhemoglobin saturation values were 97% (95%
      confidence interval [CI]: 95%, 100%) and 62% (95% CI: 51%, 73%), respectively.
      During hypoxia, maternal and fetal oxyhemoglobin saturation values decreased to
      75% (95% CI: 65%, 85%) and 23% (95% CI: 17%, 29%), respectively. Fetal BOLD
      signal intensity decreased to 81% (95% CI: 73%, 88%) in the cerebrum, 78% (95%
      CI: 67%, 89%) in the cerebellum, 83% (95% CI: 80%, 86%) in the lungs, 58% (95%
      CI: 33%, 84%) in the liver, 53% (95% CI: 43%, 64%) in the heart, and 71% (95% CI:
      48%, 94%) in the cotyledon. Correlation of fetal BOLD signal intensity was
      stronger with fetal (r = 0.91) than with maternal (r = 0.68) oxyhemoglobin
      saturation; however, the difference was not significant. The highest slope values
      were obtained for the heart: 1.68% BOLD signal intensity increase per 1% maternal
      oxyhemoglobin saturation (95% CI: 1.58, 1.77) and 1.04% BOLD signal intensity
      increase per 1% fetal oxyhemoglobin saturation (95% CI: 0.94, 1.13). CONCLUSION:
      BOLD MR imaging can be used to measure changes of oxyhemoglobin saturation in
      fetal organs during hypoxia. The liver and heart demonstrated the greatest signal
      intensity decreases during hypoxia.

PMID- 16439570
TI  - Automated spine survey iterative scan technique.
AB  - Institutional review board approval, with waived consent, was obtained to develop
      a spine-labeling algorithm with retrospectively obtained deidentified HIPAA
      compliant data. An automated magnetic resonance (MR) imaging technique to rapidly
      survey the entire spine and provide definitive numbering of disks and vertebrae
      was compared with neuroradiologist assignments in 50 cases. Contiguous two
      station sagittal fast gradient-recalled-echo sequences with 35-cm fields of view
      (FOVs) were preprogrammed for full cervical, thoracic, and lumbar spine coverage
      (combined 70-cm FOV, seven sections, 15 mm left of to 15 mm right of midline, 4
      mm section thickness, 1-mm intersection gap, 512 x 352 matrix, 58/2.0 [repetition
      time msec/echo time msec], 30 degrees flip angle, 15.6-kHz bandwidth, 42-second
      acquisition time). In all cases, the neuroradiologist could visualize and
      definitively number all cervical, thoracic, and lumbar levels on automated spine
      survey iterative scan technique localizer studies. Automated disk-vertebra
      detection and numbering were concordant with neuroradiologist assignments in all
      cases. The entire spine can be surveyed with subminute, submillimeter in-plane
      resolution MR imaging. Cervical, thoracic, and lumbar vertebrae and disks can be
      readily identified and definitively numbered by means of visual inspection or
      semiautomated computer algorithm.

PMID- 16439572
TI  - Genetic testing comes of age: WT1 mutations in steroid-resistant nephrotic
      syndrome: commentary on the article by Mucha et al. on page 325.

PMID- 16439573
TI  - Analysis of voltage-gated potassium channel beta1 subunits in the porcine
      neonatal ductus arteriosus.
AB  - The voltage-gated potassium channels (Kv) are partially responsible for the
      contraction/relaxation of blood vessels in response to changes in the Po(2)
      level. The present study determined the expression of Kvbeta1 and four oxygen
      sensitive Kvalpha subunits (Kv1.2, Kv1.5, Kv2.1, and Kv9.3) in the ductus
      arteriosus (DA), the aorta (Ao), and the pulmonary artery (PA) in porcine
      neonates immediately after birth. We cloned three Kvbeta1 transcript variants
      (Kvbeta1.2, Kvbeta1.3, and Kvbeta1.4), Kv1.2, Kv1.5, and Kv9.3 from piglets.
      Three Kvbeta1 transcripts, Kv1.2, Kv1.5, and Kv9.3, encode predicted proteins of
      401, 408, 202, 499, 600, and 491 residues. These Kv showed a high degree of
      sequence conservation with the corresponding Kv in human. Northern and
      quantitative real-time PCR (qr-PCR) analyses showed that Kvbeta1.2 expression was
      high in the DA and Ao but low in the PA. Kv1.5 expression was high in the Ao and
      PA but low in the DA. Expression of Kvbeta1.3, Kvbeta1.4, Kv1.2, Kv2.1, and Kv9.3
      was low in these blood vessels. The inactivation property of Kvbeta1.2 against
      Kv1.5 was confirmed using Xenopus laevis oocytes. Our findings suggest that the
      molecular basis for the differential electrophysiological characteristics
      including opposing response to oxygen in the DA and the PA are partially due to
      diversity in expression of Kv1.5 and Kvbeta1.2 subunits. The high expression of
      Kvbeta1.2 and relatively low expression of Kv1.5 in the DA might be partially
      responsible for the ductal closure after birth.

PMID- 16439574
TI  - Expression of the TGF-beta family of ligands is developmentally regulated in
      skeletal muscle of neonatal rats.
AB  - To dissect the possible role of the transforming growth factor-beta (TGF-beta)
      family in the regulation of skeletal muscle growth during the early postnatal
      period, the protein abundances of the TGF-beta family and their correlation with
      protein synthesis were determined in skeletal muscle of neonatal rats. To obtain
      direct evidence of the role of these growth factors in the regulation of protein
      synthesis, the TGF-beta inhibitor, follistatin, was infused into 10-d-old rats
      for 11 d and protein synthesis and phosphorylation of S6 kinase 1 (S6K1) and
      ribosomal protein (rpS6) were measured. TGF-beta2 abundance and protein synthesis
      in muscle decreased with development and were positively correlated. The
      abundances of bone morphogenetic protein 2 (BMP-2), BMP-7, and myostatin
      increased with development and were negatively correlated with protein synthesis.
      The abundances of BMP-2 and BMP-7 were positively correlated with BMP receptor IA
      (BMP-RIA) abundance. Activin A abundance was positively correlated with
      follistatin abundance and activin receptor IIB (Act-RIIB) abundance. Infusion of
      follistatin increased muscle protein synthesis and S6K1 and rpS6 phosphorylation.
      The results provide indirect and direct evidence of TGF-beta family involvement
      in the regulation of muscle protein synthesis during the neonatal period.

PMID- 16439575
TI  - Fetal cardiac natriuretic peptide expression and cardiovascular hemodynamics in
      endotoxin-induced acute cardiac dysfunction in mouse.
AB  - We hypothesized that, in acute endotoxin-induced fetal cardiac dysfunction,
      atrial (ANP) and B-type (BNP) natriuretic peptide mRNA expressions are increased
      in proportion to the severity of fetal cardiovascular compromise in mouse. To
      investigate in vitro the effect of endotoxin-induced inflammation on cardiac
      natriuretic peptide expression, fetal hearts were harvested at 15-16 d of
      gestation and incubated for 6 h with lipopolysaccharide (LPS). To examine the
      relationship between fetal cardiovascular compromise and cardiac natriuretic
      peptide expression in endotoxin-induced cardiac dysfunction in the in vivo model,
      fetuses received intra-amniotically 25 microL LPS (10 microg/mL) or 25 microL of
      0.9% saline. Fetal Doppler ultrasonography was performed before and six hours
      after the injections. In in vitro cultured fetal hearts, LPS induced the
      production of proinflammatory cytokines without affecting the basal expressions
      of natriuretic peptides. In the in vivo model, Doppler ultrasonography revealed
      severe cardiac dysfunction after LPS injection. No significant changes in ANP or
      atrial BNP mRNA were found. The fetal ventricular BNP mRNA levels were about 2.6
      fold in the LPS group compared with the control group. Decreased fetal cardiac
      outflow mean velocity, increased proportion of isovolumetric contraction time of
      the cardiac cycle, and increased pulsatility indices of the descending aorta and
      inferior vena cava were related to elevated ventricular BNP mRNA levels. Our
      results show that LPS did not increase the mRNA expression of natriuretic
      peptides in cultured fetal hearts. In contrast, fetal ventricular BNP gene
      expression was increased in proportion to the severity of the hemodynamic
      compromise in vivo.

PMID- 16439576
TI  - Hyperoxia and apoptosis in developing mouse lung mesenchyme.
AB  - Hyperoxia contributes to the development of bronchopulmonary dysplasia in former
      premature infants. Injurious environmental factors such as hyperoxia may disrupt
      distal airway branching and alveolar septation, as these critical stages in lung
      development occur following birth in extremely premature infants. To test if
      hyperoxia directly inhibited distal airway branching, we cultured E16 fetal mouse
      lung explants in either 20% (control) or 95% oxygen (hyperoxia). Hyperoxia
      reduced the number of distal airways to less than 50% of controls. Explants
      cultured in 95% oxygen also had fewer complex distal airways compared with
      controls. Mesenchymal cells adjacent to distal airways in hyperoxic explants
      appeared apoptotic by phase microscopy. Consistent with increased apoptosis,
      explants cultured in hyperoxia had increased caspase 3/7 activity compared with
      controls. Hyperoxia also increased mesenchymal caspase 3 expression and annexin V
      binding within cultured explants as visualized by fluorescence microscopy. We
      measured increased annexin V binding in isolated primary fetal lung mesenchymal
      cells cultured in 95% oxygen suggesting a direct effect on cells within the
      mesenchyme. Hyperoxia can lead to NF-kappaB activation, which mediates
      inflammatory cascades and may protect cells from apoptosis. We detected NF-kappaB
      activation and nuclear p65 localization in explants exposed to 48 h of hyperoxia.
      Inhibition of NF-kappaB prevented the hyperoxia-induced activation of caspase 3.
      NF-kappaB activation may therefore contribute to apoptosis in the developing
      fetal mouse lung following hyperoxia exposure. Our data suggest hyperoxia
      inhibits distal airway branching and directly induces apoptosis of the fetal
      mouse lung mesenchyme.

PMID- 16439577
TI  - Mouse as a model of growth retardation in cystic fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease that results in lung
      failure and premature death. A long recognized symptom of CF is growth failure,
      which is clinically relevant because it correlates with the severity of lung
      disease. We describe growth retardation in a mouse model of CF and discuss its
      potential for modeling certain aspects of human growth retardation. Mice with a
      null mutation in Cftr (cystic fibrosis transmembrance conductance regulator) were
      compared with wild-type (WT) mice at 31, 45, and 84 d of age. CF mice were
      severely growth retarded in weight and length compared with wild-type controls.
      Serum insulin like growth factor I (Igf-1) was lower in CF mice by 31-55%
      (depending on age and sex) and it significantly correlated with the size of mice
      after controlling for gender, age, and Cftr genotype. There was a marginally
      significant deficiency of serum growth hormone (Gh) in CF females, but not males.
      Our findings were consistent with models of an energy deficit in rodents. We,
      therefore, assessed food intake and found no difference between CF and WT mice,
      suggesting that CF mice had a malabsorption-mediated energy deficit. We argue
      that CF mice are suited to study the effects of intestinal disease on growth as
      well as other proposed growth-modulating processes.

PMID- 16439578
TI  - Endothelial effects of 3-hydroxyglutaric acid: implications for glutaric aciduria
      type I.
AB  - Infants with glutaric aciduria type 1 (GA1) are subject to intracranial vascular
      dysfunction. Here, we demonstrate that the disease-specific metabolite 3
      hydroxyglutaric acid (3-OH-GA) inhibits basal and vascular endothelial growth
      factor (VEGF)-induced endothelial cell migration. 3-OH-GA affects the morphology
      of VEGF-induced endothelial tubes in vitro because of partial disintegration of
      endothelial cells. These effects correlate with Ve-cadherin loss. Remarkably, 3
      OH-GA treatment of human dermal microvascular endothelial cells leads to
      disruption of actin cytoskeleton. Local application of 3-OH-GA alone or in
      combination with VEGF in chick chorioallantoic membrane induces abnormal vascular
      dilatation and hemorrhage in vivo. The study demonstrates that 3-OH-GA reduces
      endothelial chemotaxis and disturbs structural vascular integrity in vitro and in
      vivo. These data may provide insight in the mechanisms of 3-OH-GA-induced
      vasculopathic processes and suggest N-methyl-D-aspartate receptor-dependent and 
      independent pathways in the pathogenesis of GA1.

PMID- 16439579
TI  - Transcutaneous bilirubinometry: a noninvasive tool for studying newborn jaundiced
      rats before and after exposure to light.
AB  - The homozygous Gunn rat is the most frequently used animal model for the study of
      neonatal jaundice. We evaluated the applicability of noninvasive transcutaneous
      bilirubin (TcB) measurements as an index of serum total bilirubin (STB) levels in
      neonatal rats by comparison to invasive STB measurements. TcB measurements were
      made during the first 96 h of life with the Model 101 Minolta/Air-Shields
      Jaundice Meter (JM) and SpectRx BiliCheck System (BC). Measurements with both
      devices displayed parallel TcB profiles, rapidly rising within 24 h, increasing
      during the next 6 h, then leveling off after 30 h. Linear regressions for the JM
      (n = 60) were as follows: STB (mg/dL) = 0.79 (JM) - 0.01 (units, r = 0.95, head);
      STB (mg/dL) = 0.82 (JM) + 1.51 (units, r = 0.95, upper back); and STB (mg/dL) =
      0.74 (JM) + 1.60 (units, r = 0.91, lower back). Mean bias +/- imprecision were as
      follows: -0.02 +/- 3.99 mg/dL, -0.01 +/- 3.90, and 0.01 +/- 4.28 at the head,
      upper back, and lower back, respectively. For the BC, only lower back
      measurements were taken, and the regression was as follows: STB (mg/dL) = 0.77
      (BC) + 1.65 mg/dL, (r = 0.93, n = 29) with a mean bias +/- imprecision of -1.08
      +/- 3.08 mg/dL. When pups were exposed to light, correlations remained strong but
      intercepts increased. These results demonstrate that noninvasive TcB measurements
      correlate highly with STB in the Gunn rat during the first 96 h of life and after
      exposure to light. We conclude that JM measurements at the head and BC at the
      lower back reflect STB most reliably and consistently. Thus, in addition to being
      a useful tool for evaluating jaundice in human neonates, TcB methodology can be
      used successfully for the noninvasive monitoring of jaundice in neonatal Gunn
      rats pre- and postlight exposure.

PMID- 16439580
TI  - Respiratory syncytial virus infection reversed anti-asthma effect of neonatal
      Bacillus Calmette-Guerin vaccination in BALB/c mice.
AB  - Bacillus Calmette-Guerin (BCG) vaccination can protect animals from asthma, but
      the effect of BCG on childhood asthma prevention is controversial in humans. To
      verify the hypothesis that the BCG anti-asthma effect in childhood might be
      reversed by a respiratory virus infection, newborn BALB/c mice were divided into
      five groups. Control and ovalbumin (OVA) groups were mock vaccinated and mock
      infected. The BCG/OVA group was BCG vaccinated and mock infected. The respiratory
      syncytial virus (RSV)/OVA group was mock vaccinated and RSV infected. The
      BCG/RSV/OVA group was BCG vaccinated and RSV infected. Except for the control
      group, all groups underwent OVA sensitization and challenge. Airway
      hyperresponsiveness (AHR) was measured after challenge and cells in
      bronchoalveolar lavage fluid (BALF) were counted. Cytokines in BALF and serum OVA
      specific IgE were detected by ELISA and inflammatory characteristics of lung
      sections were scored. Mice with neonatal BCG vaccination (BCG/OVA group) were
      significantly protected from BALF eosinophilia, AHR to methacholine,
      peribronchiolitis, alveolitis, and peribronchial eosinophilia in comparison with
      the OVA, RSV/OVA, and BCG/RSV/OVA groups. AHR in the OVA group was greater than
      in the BCG/OVA group but lower than in the RSV/OVA and BCG/RSV/OVA groups. No
      significant differences in BALF eosinophilia, AHR, and lung inflammation were
      found between the RSV/OVA and BCG/RSV/OVA groups. The impact of BCG vaccination
      on anti-asthma in mice was not dependent on interferon-gamma, IL-4, and IL-10
      levels. The results suggested that RSV infection can reverse the anti-asthma
      effect of neonatal BCG vaccination in BALB/c mice.

PMID- 16439581
TI  - The production of hydroxyl radicals in the fetal lamb brain resulting from
      occlusion of the umbilical circulation and the transplacental effect of MCI-186
      to inhibit hydroxyl radical production.
AB  - The present study evaluated hydroxyl radical production in fetal lamb brain
      during and after umbilical cord occlusion and examined the effects of injecting
      MCI-186 (3-metyl-1-phenyl-2-pyrazolin-5-one; Edaravone), a hydroxyl radical
      scavenger, into the maternal circulation. In 11 chronically instrumented lambs,
      intermittent total umbilical cord occlusions 1 min out of every 3 min for 1 h and
      10-min persistent total umbilical cord occlusion were performed with brain
      microdialysis using 5 mM of sodium salicylate. In the remaining four lambs, 60 mg
      of MCI-186 was administered into the maternal circulation from shortly before the
      end of 10-min persistent total umbilical cord occlusion. Concentrations of 2,3
      dihydroxy-benzoic acid (2,3-DHBA), produced by hydroxyl radical reactions with
      sodium salicylate, were measured in perfusate by HPLC. Concentration of 2,3-DHBA
      in perfusate was 23.05 +/- 10.95 nM before umbilical cord occlusion. Levels of
      2,3-DHBA tended to increase slightly during and after intermittent umbilical cord
      occlusion, and were significantly increased by the end of 10-min occlusion (40.06
      +/- 21.36 nM) and after occlusion (93.74 +/- 29.17 nM). Infusion of MCI-186
      suppressed 2,3-DHBA concentration to 29.35 +/- 14.95 nM after occlusion.
      Administration of MCI-186 into the maternal circulation reduces hydroxyl radical
      production induced by umbilical cord occlusion in the fetal lamb brain.

PMID- 16439582
TI  - Cerebral cortical tissue damage after hemorrhagic hypotension in near-term born
      lambs.
AB  - Hypotension reduces cerebral O(2) supply, which may result in brain cell damage
      and loss of brain cell function in the near-term neonate. The aim is to elucidate
      1) to what extent the functional disturbance of the cerebral cortex, as measured
      with electrocortical brain activity (ECBA), is related to cerebral cortical
      tissue damage, as estimated by MAP2; and 2) whether there is a relationship
      between the glutamate, nitric oxide (NO), cGMP pathway and the development of
      cerebral cortical tissue damage after hemorrhagic hypotension. Seven lambs were
      delivered at 131 d of gestation. Hypotension was induced by withdrawal of blood
      until mean arterial blood pressure was reduced to 30% of normotension. Cerebral
      O(2) supply, consumption, and ECBA were calculated in normotensive conditions and
      after 2.5 h of hypotension. Concentrations of glutamate and aspartate in
      cerebrospinal fluid (CSF), NO(2) and NO(3) (NOx) in plasma, and cGMP in cortical
      brain tissue were determined in both conditions. CSF and brain tissue from
      siblings were used to determine normotensive values. Cortical neuronal damage was
      detected after 2.5 h of hypotension. ECBA was negatively related to the severity
      of the cortical damage. ECBA was related to respectively glutamate, NOx, and cGMP
      concentrations. In conclusion, cortical neuronal damage is detected after 2.5 h
      of hemorrhagic hypotension in the near-term born lamb. The damage is reflected by
      a reduction of ECBA. The glutamate, NOx, cGMP pathway is likely to be involved in
      the pathogenesis of cerebral cortical damage.

PMID- 16439583
TI  - N-methyl-isobutyl-amiloride ameliorates brain injury when commenced before
      hypoxia ischemia in neonatal mice.
AB  - Underphysiologic conditions, brain intracellular pH (pH(i)) is maintained at
      7.03. Rebound brain intracellular alkalosis has been observed in experimental
      models and adult stroke after hypoxia/ischemia (HI). In term infants with
      neonatal encephalopathy (NE), an association exists between the magnitude of
      brain alkalosis and neurodevelopmental outcome, and there is increasing evidence
      to suggest that alkalosis may be deleterious to cell survival. Activation of the
      Na(+)/H(+) exchanger (NHE) is thought to be responsible for the rapid
      normalization of pH(i) and rebound alkalosis after reperfusion. We hypothesized
      that N-methyl-isobutyl-amiloride (MIA), an inhibitor of the NHE, would reduce
      brain injury in a model of neonatal HI. Seven-day-old mice underwent left carotid
      artery occlusion followed by exposure to 8% oxygen for 30 min (moderate insult)
      or 1 h (severe insult). Animals received MIA or saline 8 hourly starting 30 min
      before HI. Outcome was determined at 48 h by measuring viable tissue in the
      injured hemisphere (severe insult) or injury score and TUNEL staining (moderate
      insult). After the severe insult, MIA had a significant neuroprotective effect
      increasing forebrain tissue survival from 44% to 67%. After the moderate insult,
      damage was localized to the hippocampus where treatment resulted in a significant
      reduction in injury score and in TUNEL-positive cells. MIA was also shown to have
      a significant overall neuroprotective effect based on injury score after the
      moderate insult. Amiloride analogues are neuroprotective when commenced before HI
      in a mouse model.

PMID- 16439584
TI  - Selective inhibition of nuclear factor-kappaB activation after hypoxia/ischemia
      in neonatal rats is not neuroprotective.
AB  - Activated nuclear factor-kappaB (NFkappaB) has been shown to increase
      transcription of several genes that could potentially contribute to neuronal
      damage, such as proinflammatory cytokines, chemokines, and inducible nitric oxide
      synthase. The aim of our study was to investigate whether inhibition of NFkappaB
      activation could prevent hypoxia/ischemia (HI)-induced cerebral damage in
      neonatal rats. We used a cell permeable peptide (NEMO binding domain [NBD]
      peptide) that is known to prevent the association of the regulatory protein NEMO
      with IKK, the kinase that activates NFkappaB. Via this mechanism, the NBD peptide
      can specifically block the activation of NFkappaB, without inhibiting basal
      NFkappaB activity. Cerebral HI was induced in neonatal rats by occlusion of the
      right carotid artery followed by 90 min of hypoxia (Fio(2) = 0.08). Immediately
      upon reoxygenation, as well as 6 and 12 h later, rats were treated with vehicle
      or NBD peptide (20 mg/kg i.p.). Histologic analysis of brain damage was performed
      at 6 wk after HI. To assess NFkappaB activation, electromobility shift assays
      (EMSAs) were performed on brain nuclear extracts obtained 6 h after
      reoxygenation. Increased NFkappaB activity could be shown at 6 h after HI in both
      hemispheres. Peripheral administration of NBD peptide prevented this HI-induced
      increase in NFkappaB activity in both hemispheres. Histologic analysis of long
      term cerebral damage revealed that inhibition of NFkappaB activation by
      administration of NBD peptide at 0, 6, and 12 h after HI resulted in an increment
      of neuronal damage. In conclusion, our data suggest that inhibition of NFkappaB
      activation using NBD peptide early after HI increases brain damage in neonatal
      rats.

PMID- 16439585
TI  - Treatment of experimental status epilepticus in immature rats: dissociation
      between anticonvulsant and antiepileptogenic effects.
AB  - We studied the effects of treating status epilepticus (SE) induced by lithium and
      pilocarpine at postnatal day 15 (P15) or 28 (P28), on the severity of acute SE
      and of SE-induced epileptogenesis. Rats received topiramate (10 or 50 mg/kg, IP)
      or diazepam (5 mg/kg, IP) 20, 40 or 70 min after pilocarpine, and three months
      after SE 24-h video/EEG recordings were obtained for one (P28) or two weeks (P15)
      continuously. In P15 rats, topiramate did not modify the course of SE, yet
      treatment at 20 or 40 min completely prevented the development of spontaneous
      recurrent seizures (SRS) while later treatment (70 min) was partially effective
      in reducing the severity and frequency of SRS. Diazepam was effective against
      acute SE at all time points tested. Early (20 min) but not late treatment with
      diazepam had the effect of reducing the frequency and severity of SRS. In P28
      rats, both drugs reduced the cumulative seizure time. Early treatment (20 min)
      with either drug reduced the incidence of chronic epilepsy. Late treatment (40/70
      min) did not alter the incidence of SRS, but decreased their frequency. This
      study demonstrates that, in the treatment of SE, anticonvulsant and
      antiepileptogenic effects can be dissociated in a development-specific manner:
      topiramate was antiepileptogenic without being an effective anticonvulsant in P15
      animals at the doses tested. Diazepam, on the other hand, was a better
      anticonvulsant than an antiepileptogenic agent in the P15 animals at the dose
      tested. Such effects were not seen in the older animals.

PMID- 16439586
TI  - Spastic paresis after perinatal brain damage in rats is reduced by human cord
      blood mononuclear cells.
AB  - Brain damage around birth may cause lifelong neurodevelopmental deficits. We
      examined the therapeutic potential of human umbilical cord blood-derived
      mononuclear cells containing multipotent stem cells to facilitate motor recovery
      after cerebral hypoxic-ischemic damage in neonatal rats. Left carotid artery
      ligation followed by 8% O(2) inhalation for 80 min was performed on postnatal d
      7, succeeded by intraperitoneal transplantation of human umbilical cord blood
      derived mononuclear cells on postnatal d 8 in a sham-controlled design.
      Histologic and immunohistochemical analysis on postnatal d 21 revealed that
      neonates developed severe cerebral damage after the hypoxic-ischemic insult.
      These animals also suffered from contralateral spastic paresis, as evidenced by
      their locomotor behavior. After transplantation of human umbilical cord blood
      derived mononuclear cells, spastic paresis was largely alleviated, resulting in a
      normal walking behavior. This "therapeutic" effect was accompanied by the fact
      that mononuclear cells had entered the brain and were incorporated around the
      lesion without obvious signs of transdifferentiation. This study demonstrates
      that intraperitoneal transplantation of human umbilical cord blood-derived
      mononuclear cells in a rat model of perinatal brain damage leads to both
      incorporation of these cells in the lesioned brain area and to an alleviation of
      the neurologic effects of cerebral palsy as assessed by footprint and walking
      pattern analysis.

PMID- 16439587
TI  - Placental LPL gene expression is increased in severe intrauterine growth
      restricted pregnancies.
AB  - Intrauterine growth restriction (IUGR) is associated with reduced placental
      supply of nutrients to the fetus. Lipoprotein lipase (LPL) mediates the
      hydrolysis of triglycerides from maternal lipoproteins to obtain fatty acids.
      Here, we tested the hypothesis that placental LPL gene expression level is
      altered in pregnancies complicated by IUGR. To this purpose, 28 IUGR fetuses were
      identified during pregnancy and divided in two groups: 7 M-IUGR ["mild" IUGR,
      with normal umbilical artery pulsatility index (PI)] and 21 S-IUGR ("severe"
      IUGR, with abnormal PI). Moreover, 10 out of 28 IUGR pregnancies were associated
      with preeclampsia. Controls were 19 normal pregnancies delivering appropriate for
      gestational age (AGA) fetuses. Relative real-time quantification of LPL was
      carried out in RNA from placental chorionic villi by the DeltaDeltaCt method,
      using beta-actin as normalizing gene. Placental LPL mRNA expression levels were
      significantly higher in IUGR than in AGA. In particular, significantly higher
      values were observed in S-IUGR, independent from the concomitant association with
      preeclampsia. No significant relationship was observed between placental LPL mRNA
      expression levels or gestational age. In conclusion, placental LPL mRNA gene
      expression is increased in severe IUGR, characterized by enhanced vascular
      placental resistances and alterations of placental nutrient transport.

PMID- 16439588
TI  - Cytokines in the placenta of Pakistani newborns with and without intrauterine
      growth retardation.
AB  - Although intrauterine growth retardation (IUGR) is a major risk factor for
      increased neonatal mortality and morbidity, the mechanisms behind it are not
      clear. We analyzed cytokine gene expression and gene polymorphisms in infants
      with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55
      control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-alpha, TGF
      beta, IL-6, IL-4, IL-1beta, IL-12, IFN-gamma and GAPDH was quantified with RT-PCR
      from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, 
      308TNFA, -174IL6, +915TGFB1, intron 2 IL1RN, +36TNFR1, 150V IL4RA and -159CD14
      were determined from genomic DNA. The serum levels of IL-1beta, IL-6, IL-8, IL
      10, IL-12, TNF-alpha and TGF-beta were measured. There was a significant decrease
      of IL-10 and IL-12, but increase of TGF-beta in the decidua and similarly
      decrease of IL-10, but increase of TGF-beta in the trophoblasts of the IUGR
      placentas compared with the non-IUGR placentas. We found significantly lower
      levels of IL-1beta in serum from the mothers of the IUGR infants and of TGF-beta
      in serum of the infants with IUGR compared with the non-IUGR infants. We note
      that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF
      beta mRNA up-regulated in IUGR placentas of mothers from a population with
      multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may
      be involved in the pathogenesis of IUGR and might possibly be treatable.

PMID- 16439589
TI  - Patterns of growth and body proportions after total-body irradiation and
      hematopoietic stem cell transplantation during childhood.
AB  - Patterns of growth and body proportions were studied in 75 children receiving
      total-body irradiation (TBI) and hematopoietic stem cell transplantation (SCT)
      before onset of puberty. Of the 19 patients receiving GH, only data obtained
      before onset of GH were included. Thirty-two patients reached final height (FH).
      Median change in height SD score (SDS) between SCT and FH was -1.7 in boys and 
      1.1 in girls. Peak height velocity (PHV) was decreased in the majority of the
      patients (median PHV 5.7 cm/y in boys and 5.3 cm/y in girls), even though it
      occurred at appropriate ages. Changes in body proportions were analyzed by linear
      mixed-effects models. Decrease in sitting height SDS did not differ between boys
      and girls. In boys, decrease in leg length SDS was of comparable magnitude,
      whereas, in girls, decrease in leg length was less pronounced, leading to a
      significant decrease in SDS for sitting height/height ratio in girls only. The
      sex-specific effects of several variables on height SDS were analyzed by linear
      mixed-effects modeling, showing a slightly faster decrease in younger children
      and a more pronounced decrease during puberty in boys compared with girls. We
      conclude that 1) younger children are more susceptible to growth retardation
      after TBI and SCT, 2) pubertal growth is more compromised in boys, and 3) leg
      growth is relatively less affected in girls, possibly due to a high incidence of
      gonadal failure in girls.

PMID- 16439590
TI  - High protein pre-term infant formula: effect on nutrient balance, metabolic
      status and growth.
AB  - Several lines of evidence suggest that formula with protein content of 3.0 g/100
      kcal does not fully meet the protein needs of very-low-birth weight infants. Our
      purpose was to compare nitrogen balance, metabolic status and growth in infants
      fed a standard (3.0 g/100 kcal; RegPro) and high (3.6 g/100 kcal; HiPro) protein
      infant formula. Infants were fed both formulas, each formula for one week in
      balanced cross-over design. Metabolic status was monitored throughout. Nutrient
      balance and plasma amino acids were determined at the end of each week. Data were
      analysed using a linear mixed model. Eighteen infants were studied. Nine infants
      received the RegPro and nine received HiPro formula first. Nitrogen intake,
      absorption and retention were greater with the HiPro formula. None of the infants
      developed uremia or metabolic acidosis but retinol-binding-protein and weight
      gain were greater with the HiPro formula. Increased protein accretion paralleled
      by better weight gain without evidence of metabolic stress indicates that a
      formula with a protein content of 3.6 g/100 kcal better meets protein needs in
      these rapidly-growing infants. Further studies are needed to determine whether
      these short-term outcomes will be translated into long-term benefits.

PMID- 16439591
TI  - Variation in [U-13C] alpha linolenic acid absorption, beta-oxidation and
      conversion to docosahexaenoic acid in the pre-term infant fed a DHA-enriched
      formula.
AB  - Docosahexaenoic acid (DHA) is an integral component of neural cell membranes and
      is critical to the development and function of the CNS. A premature delivery
      interrupts normal placental supply of DHA such that the infant is dependent on
      the nature of the nutritional support offered. The most abundant omega-3 fatty
      acid in pre-term formulas is alpha linolenic acid (ALNA), the precursor of DHA.
      This project studied the absorption, beta-oxidation and conversion of ALNA to DHA
      by pre-term infants ranging from 30-37 wk of corrected gestation. [U-(13)C] ALNA
      was administered emulsified with a pre-term formula to 20 well pre-term infants
      on full enteral feeds. Enrichment of (13)C in stool and as (13)CO(2) in breath
      was used to estimate absorption across the gut and partitioning toward beta
      oxidation respectively. Excretion of the administered dose of (13)C in stool
      ranged from 2.0 to 26.2%; excretion decreased with increasing birth gestation.
      Appearance as (13)CO(2) on breath ranged from 7.6 to 19.0%. All infants
      synthesised eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and DHA with
      the least mature having the highest cumulative plasma DHA. These results show
      considerable variation suggesting that the worst absorption of ALNA and the
      greatest production of DHA occur in infants born at the earliest gestation.

PMID- 16439592
TI  - Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as
      having 21-hydroxylase deficiency and/or aromatase deficiency: diagnostic value of
      urine steroid hormone analysis.
AB  - In this study, we report on three Japanese patients with cytochrome P450
      oxidoreductase (POR) deficiency (PORD). Case one was a 46,XY patient who was
      found to have mildly increased 17alpha-hydroxyprogesterone (17-OHP) by the
      neonatal mass screening. There was no maternal virilization during pregnancy, and
      he had no skeletal or genital abnormality. Thus, he was initially diagnosed as
      having nonclassical 21-hydroxylase deficiency (21-OHD). Cases two and three were
      46,XX patients who were identified because of severely virilized external
      genitalia and maternal virilization during pregnancy. In case two, the neonatal
      mass screening was normal, and she had no skeletal abnormality except for mild
      adduction of bilateral third toes. Thus, she was initially diagnosed as having
      aromatase deficiency. In case three, the neonatal mass screening showed
      moderately increased 17-OHP, and no skeletal lesion other than rigid second
      metacarpophalangeal joints was identified in early infancy. Thus, she was
      initially suspected as having 21-OHD and/or aromatase deficiency. Subsequently,
      endocrine studies including urine steroid hormone analysis were performed for the
      assessment of glucocorticoid treatment in case one and for the virilized
      genitalia in cases two and three, showing adrenal and/or gonadal dysfunction
      characteristic of PORD. Thus, molecular analysis of POR was carried out,
      demonstrating homozygosity for R457H in cases one through three. The results
      imply that clinical features in PORD can be similar to those in 21-OHD or
      aromatase deficiency, and that comprehensive assessment of the pregnant course,
      physical examination, and adrenal and gonadal function studies is essential for
      the precise diagnosis of PORD.

PMID- 16439593
TI  - Elevated serum levels of the decoy receptor osteoprotegerin in children with
      Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is characterized by an accumulation of
      dendritic Langerhans cells in granulomatous lesions in the bone, skin, and other
      sites in the body. The pathogenesis of the disease remains unknown. We measured
      serum levels of the decoy receptor osteoprotegerin (OPG), an important regulator
      of bone metabolism as well as immune responses, in 18 children with single system
      (SS) or multi-system (MS) forms of LCH and 20 pediatric controls. OPG levels were
      significantly increased in LCH patients at diagnosis when compared with controls,
      and pretreatment levels of OPG were elevated in MS compared with SS patients.
      Moreover, OPG levels in LCH patients were elevated in patients with involvement
      of risk organs (liver, lungs, hematopoietic system, or spleen) when compared with
      patients without risk organ involvement, indicative of an association between OPG
      values and disease severity. We also observed a positive correlation between
      serum levels of OPG and tumor necrosis factor (TNF)-alpha, a pro-inflammatory
      cytokine, at the time of onset of disease. These findings show, for the first
      time, that serum OPG levels are elevated in LCH patients, and suggest that OPG
      may play a role in the pathogenesis of this enigmatic disease.

PMID- 16439594
TI  - Decreased intracellular ATP content and intact mitochondrial energy generating
      capacity in human cystinotic fibroblasts.
AB  - Cystinosis is an autosomal recessive lysosomal storage disorder caused by a
      defect in the lysosomal cystine carrier cystinosin. Cystinosis is the most common
      cause of inherited Fanconi syndrome leading to renal failure, in which the
      pathogenesis is still enigmatic. Based on studies of proximal tubules loaded with
      cystine dimethyl ester (CDME), altered mitochondrial adenosine triphosphate (ATP)
      production was proposed to be an underlying pathologic mechanism. Thus far,
      however, experimental evidence supporting this hypothesis in humans is lacking.
      In this study, energy metabolism was extensively investigated in primary
      fibroblasts derived from eight healthy subjects and eight patients with
      cystinosis. Patient's fibroblasts accumulated marked amounts of cystine and
      displayed a significant decrease in intracellular ATP content. Remarkably,
      overall energy-generating capacity, activity of respiratory chain complexes,
      ouabain-dependent rubidium uptake reflecting Na,K-ATPase activity, and bradykinin
      stimulated mitochondrial ATP production were all normal in these cells. In
      conclusion, the data presented demonstrate that mitochondrial energy-generating
      capacity and Na,K-ATPase activity are intact in cultured cystinotic fibroblasts,
      thus questioning the idea of altered mitochondrial ATP synthesis as a keystone
      for the pathogenesis of cystinosis.

PMID- 16439595
TI  - Cryptogenic liver disease in four children: a novel congenital disorder of
      glycosylation.
AB  - We investigated the metabolic defect(s) of four children who presented with
      isolated cryptogenic chronic liver disease, coagulopathy, and abnormalities of
      several unrelated serum glycoproteins. Analysis of the patients' serum
      glycoproteins and fibroblasts suggest they have a novel congenital disorder of
      glycosylation (CDG). All had abnormal transferrin (Tf) isoelectric focusing (IEF)
      profiles. More detailed analysis of Tf by electrospray ionization mass
      spectrometry (ESI-MS) showed a plethora of abnormal glycosylations that included
      loss of 1-2 sialic acids and 1-2 galactose units, typical of Group II defects. Tf
      from two patients also lacked 1-2 entire oligosaccharide chains, typical of Group
      One disorders. Total serum N-glycans were analyzed by HPLC and matrix-assisted
      laser desorption/ionization mass spectrometry and also showed increased
      proportion of neutral glycan chains lacking sialic acids and galactose units.
      Analysis of patient fibroblasts eliminated CDG-Ia, through CDG-Ih, -IL and CDG
      IId. Our results suggest that a subset of children with clinically asymptomatic,
      cryptogenic hypertransaminasemia and/or liver steato-fibrosis may represent a
      novel type of CDG-X with an unknown defect(s). Clinicians are encouraged to test
      such patients for abnormal Tf glycosylation by ESI-MS.

PMID- 16439597
TI  - Early maturation of evoked otoacoustic emissions and medial olivocochlear reflex
      in preterm neonates.
AB  - The present study was designed to investigate the early maturation of the
      brainstem regulation of the cochlear function in preterm neonates. Evoked
      otoacoustic emissions (EOAE) and their regulation via the medial olivocochlear
      efferent (MOC) reflex were investigated in a large population of preterm neonates
      and compared with full-term neonates and young babies from birth to 4 y and
      school-aged children. In 28-wk preterm neonates, EOAE were seen in the mid
      frequency range. These responses extended both to the low (down to 1025 Hz) and
      high (up to 6152 Hz) frequency ranges at 38 wk of gestational age and remained
      stable up to 4 mo. At this stage, the amplitude of EOAE overlapped adult values.
      EOAE amplitudes then decreased to reach adult values at 3 y of age. Maturation of
      MOC efferents innervating the outer hair cells was investigated by studying the
      suppressive effect of contralateral sound on the EOAE amplitudes (MOC reflex).
      The first MOC responses were recorded in preterm neonates of 32-33 wk of
      gestational age, reaching adult-like values at 37 wk of gestational age. The
      maximum effect of MOC efferent activation occurred between 2000 and 4000 Hz.
      These results suggest that, in humans, MOC efferents mature in utero. Thus,
      testing the MOC reflex may have a clinical relevance to detect an abnormal
      development of the auditory pathways, particularly of a brainstem circuitry not
      explored through conventional testing.

PMID- 16439598
TI  - Neonatal hydrocortisone treatment related to 1H-MRS of the hippocampus and short
      term memory at school age in preterm born children.
AB  - Animal studies have shown that corticosteroids (dexamethasone) cause neuronal
      loss in the hippocampus and deficits in short term memory. Proton magnetic
      resonance spectroscopy can measure brain metabolites in vivo and give an
      indication of neuronal integrity. We investigated whether prolonged
      administration of hydrocortisone during the neonatal period for bronchopulmonary
      dysplasia (BPD) in preterm born children changes the metabolism in the
      hippocampus, measured at school age. Secondly, we investigated whether
      hippocampal metabolism and short-term memory and neurodevelopmental outcome are
      related. In this observational study 37 preterm born children (< or = 32 wk
      (range 25.0-33.0) and/or a birth weight < or = 1500 g) underwent proton
      spectroscopy of the hippocampus at school age. Eighteen children were treated
      with hydrocortisone for BPD (starting dose 5 mg/kg/d tapered over a minimum
      period of 22 d, median duration 28 d) and 19 never received corticosteroids
      during the perinatal period. N-acetyl aspartate/ Choline +
      Creatine/phosphocreatine (NAA/(Cho + Cr)) ratios were determined. A 15-word
      recall memory test and an IQ measurement were obtained on the same day.
      Hydrocortisone treated children were younger, lighter and sicker than their
      nonsteroid treated counterparts. Mean NAA/(Cho + Cr) ratios in the hippocampus
      were not significantly different in the hydrocortisone group compared with the
      non-steroid group. Performance on the 15-word memory test and IQ were similar in
      the two groups. There was no relation between NAA/(Cho + Cr) ratios and memory
      nor between NAA/(Cho + Cr) ratios and IQ. We conclude that hydrocortisone in the
      mentioned dose, administered in the neonatal period for BPD, does not appear to
      have any long-term effects on memory and/or hippocampal metabolism.

PMID- 16439599
TI  - Relationship between blood pressure, cerebral electrical activity, cerebral
      fractional oxygen extraction, and peripheral blood flow in very low birth weight
      newborn infants.
AB  - There is uncertainty about the level of systemic blood pressure required to
      maintain adequate cerebral oxygen delivery and organ integrity. This prospective,
      observational study on 35 very low birth weight infants aimed to determine the
      mean blood pressure (MBP) below which cerebral electrical activity, peripheral
      blood flow (PBF), and cerebral fractional oxygen extraction (CFOE) are abnormal.
      Digital EEG, recorded every day on the first 4 d after birth, were analyzed a) by
      automatic spectral analysis, b) by manual measurement of interburst interval, and
      c) qualitatively. CFOE and PBF measurements were performed using near-infrared
      spectroscopy and venous occlusion. MBP was measured using arterial catheters. The
      median (range) of MBP recorded was 32 mm Hg (16-46). The EEG became abnormal at
      MBP levels below 23 mm Hg: a) the relative power of the delta (0.5-3.5 Hz)
      frequency band was decreased, b) interburst intervals were prolonged, and c) all
      four qualitatively abnormal EEG (low amplitude and prolonged interburst
      intervals) from four different patients were recorded below this MBP level. The
      only abnormally high CFOE was measured at MBP of 20 mm Hg. PBF decreased at MBP
      levels between 23 and 33 mm Hg. None of the infants in this study developed
      cystic periventricular leukomalacia. One infant (MBP, 22 mm Hg) developed
      ventricular dilatation after intraventricular hemorrhage. The EEG and CFOE
      remained normal at MBP levels above 23 mm Hg. It would appear that cerebral
      perfusion is probably maintained at MBP levels above 23 mm Hg.

PMID- 16439596
TI  - Variability in cerebral oxygen delivery is reduced in premature neonates exposed
      to chorioamnionitis.
AB  - Premature infants exposed to chorioamnionitis are at increased risk for
      periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH), lesions
      that may result from inflammation and/or fluctuations in cerebral blood flow. The
      effect of chorioamnionitis on near-infrared spectroscopy (NIRS) measures of
      cerebral oxygen delivery has not been evaluated previously. Forty-nine infants
      born at 25-31 6/7 wk gestation underwent NIRS examination on d 1, 2, 3, and 7 of
      life. Variability in NIRS tracings was analyzed by partitioning each tracing into
      three components: long-term, intermediate, and short-term variability; the latter
      two components were analyzed. Chorioamnionitis-exposed infants manifest reduced
      intermediate variability in cerebral oxygenated and deoxygenated Hb but not total
      Hb. Infants with severe IVH/PVL had the lowest intermediate variability on d 1.
      Short-term variability was similar between chorioamnionitis-exposed and unexposed
      infants, and between infants with versus without severe IVH or PVL. We conclude
      that intermediate-term variability in NIRS cerebral oxygen delivery is reduced in
      chorioamnionitis-exposed infants. We speculate that intermediate variability
      represents the important time frame for evaluating the pathogenesis of perinatal
      brain injury. Further studies are needed to determine how these findings relate
      to cerebral blood flow autoregulation and oxygen utilization in premature
      infants.

PMID- 16439600
TI  - Maternal preeclampsia predicts elevated blood pressure in 12-year-old children:
      evaluation by ambulatory blood pressure monitoring.
AB  - Ambulatory blood pressure (ABP) monitoring offers a reliable method for
      determining blood pressure (BP) in children. The aim of this cohort study was to
      examine whether maternal preeclampsia is associated with elevated BP in an
      offspring. The study population consisted of 57 children born to preeclamptic
      mothers (PRE) and their 57 age- and sex-matched control subjects born to
      normotensive mothers (non-PRE). We examined the 24-h ABP at 12 y of age in the
      PRE and non-PRE children. Within the two groups, the association of
      anthropometric measures, plasma catecholamine (epinephrine [E], norepinephrine
      [NE]) concentrations, and ABP was examined. The PRE children had significantly
      higher mean 24-h systolic and diastolic ABPs than the non-PRE children. The same
      was true for the mean daytime and nighttime systolic and diastolic ABPs. The PRE
      boys had higher 24-h systolic ABP than the PRE girls. In the PRE children, high
      plasma E concentration and being born small for gestational age (SGA) predicted
      high systolic 24-h ABP in logistic regression analysis. In the non-PRE children,
      high current body mass index (BMI) and high plasma E concentration was associated
      with high systolic 24-h ABP. In conclusion, systolic and diastolic ABP values
      were elevated in the PRE children. High plasma E concentration and being born SGA
      were associated with high systolic 24-h ABP in the PRE children. Presumably
      maternal preeclampsia affects offspring via several mechanisms, including genetic
      ones and metabolic consequences of restricted intrauterine growth.

PMID- 16439601
TI  - Mutations in the Wilms' tumor 1 gene cause isolated steroid resistant nephrotic
      syndrome and occur in exons 8 and 9.
AB  - Primary steroid-resistant nephrotic syndrome (SRNS) is characterized by childhood
      onset of proteinuria and progression to end-stage renal disease. Approximately 10
      25% of familial and sporadic cases are caused by mutations in NPHS2 (podocin).
      Mutations in exons 8 and 9 of the WT1 gene have been found in patients with
      isolated SRNS and in SRNS associated with Wilms' tumor (WT) or urogenital
      malformations. However, no large studies have been performed to date to examine
      whether WT1 mutations in isolated SRNS are restricted to exons 8 and 9. To
      address this question, we screened a worldwide cohort of 164 cases of sporadic
      SRNS for mutations in all 10 exons of the WT1 gene by multiplex capillary
      heteroduplex analysis and direct sequencing. NPHS2 mutations had been excluded by
      direct sequencing. Fifteen patients exhibited seven different mutations
      exclusively in exons 8 and 9 of WT1. Although it is possible that pathogenic
      mutations of WT1 may also reside in the introns, regions of the gene that were
      not able to be screened in this study, these data together with our previous
      results (Ruf et al.: Kidney Int 66: 564-570, 2004) indicate that screening of WT1
      exons 8 and 9 in patients with sporadic SRNS is sufficient to detect pathogenic
      WT1 mutations and may open inroads into differential therapy of SRNS.

PMID- 16439602
TI  - Impaired activity of the gamma-glutamyl cycle in nephropathic cystinosis
      fibroblasts.
AB  - Cystinotic patients have been shown to excrete in their urine high levels of
      pyroglutamate, an intermediate metabolite of the adenosine triphosphate (ATP)
      dependent gamma-glutamyl cycle, which is responsible for glutathione (GSH)
      synthesis. Human fibroblasts were used to study the mechanisms leading to
      pyroglutamate accumulation in nephropathic cystinosis (NC). We show that
      inhibition of ATP synthesis caused a marked intracellular accumulation of
      pyroglutamate, reflecting decreased GSH synthesis. Despite similar degrees of ATP
      depletion, pyroglutamate increased more in cystinotic fibroblasts than in
      controls, while GSH decreased to lower levels. In addition, cystinotic cells
      exposed to oxidative stress (hydrogen peroxide) were unable to increase their GSH
      concentration above baseline. These results could not be attributed to
      differences in mitochondrial oxidative activity or to increased apoptotic cell
      death. Together, these results support the hypothesis that cysteine derived from
      lysosomal cystine efflux limits the activity of the gamma-glutamyl cycle and GSH
      synthesis.

PMID- 16439603
TI  - Charge selective function in childhood glomerular diseases.
AB  - The charge selectivity (CS) function in human renal disease has not been
      unequivocally demonstrated to date. However, the clearance ratio of IgA to IgG
      may be theoretically useful in estimating CS in humans, since IgA and IgG have
      similar sizes and tertiary structures, but distinct isoelectric points (3.5-5.5
      [IgA] and 4.5-9.0 [IgG]), and Stokes-Einstein radius: 61 A (IgA) and 49-60 A
      (IgG). Two-dimensional electrophoresis with the following immunoblotting revealed
      that the considerably anionic portion (isoelectric points [pI] <4.0) of IgA,
      visible in serum, was absent in the urine in steroid-sensitive nephrotic syndrome
      (SSNS) but present in the same during IgA nephropathy (IgAN) and
      membranoproliferative glomerulonephritis (MPGN). A latex assay revealed the CS
      index (CSI) was significantly low in patients with podocyte disease (group A),
      including SSNS, focal and segmental glomerulosclerosis (FSGS) and Finnish-type
      congenital nephrotic syndrome (FCNS), but high in those with Alport syndrome
      (AS), IgAN, Henoch-Schonlein purpura nephritis (HSPN), and MPGN (group B). The
      linear regression analysis of the IgA size selectivity index (IgA SSI; clearance
      ratio of IgA to transferrin) and SSI (clearance ratio of IgG to transferrin),
      which represents the clearance ratio of IgA to IgG referring to the transferrin
      clearance, revealed the influence of the charge more accurately. Indeed, the
      slope of the regression lines of IgA SSI (y) to SSI (x) were concluded to be y =
      0.39x (group A) and y = 1.05x (group B), respectively. These results suggested
      that the charge selective barrier among podocyte diseases (group A) is preserved
      to some degree, but lost in cases of nephritis and AS (group B).

PMID- 16439604
TI  - Methodologic European external quality assurance for DNA sequencing: the EQUALseq
      program.
AB  - BACKGROUND: DNA sequencing is a key technique in molecular diagnostics, but to
      date no comprehensive methodologic external quality assessment (EQA) programs
      have been instituted. Between 2003 and 2005, the European Union funded, as
      specific support actions, the EQUAL initiative to develop methodologic EQA
      schemes for genotyping (EQUALqual), quantitative PCR (EQUALquant), and sequencing
      (EQUALseq). Here we report on the results of the EQUALseq program. METHODS: The
      participating laboratories received a 4-sample set comprising 2 DNA plasmids, a
      PCR product, and a finished sequencing reaction to be analyzed. Data and
      information from detailed questionnaires were uploaded online and evaluated by
      use of a scoring system for technical skills and proficiency of data
      interpretation. RESULTS: Sixty laboratories from 21 European countries
      registered, and 43 participants (72%) returned data and samples. Capillary
      electrophoresis was the predominant platform (n = 39; 91%). The median contiguous
      correct sequence stretch was 527 nucleotides with considerable variation in
      quality of both primary data and data evaluation. The association between
      laboratory performance and the number of sequencing assays/year was statistically
      significant (P <0.05). Interestingly, more than 30% of participants neither added
      comments to their data nor made efforts to identify the gene sequences or
      mutational positions. CONCLUSIONS: Considerable variations exist even in a highly
      standardized methodology such as DNA sequencing. Methodologic EQAs are
      appropriate tools to uncover strengths and weaknesses in both technique and
      proficiency, and our results emphasize the need for mandatory EQAs. The results
      of EQUALseq should help improve the overall quality of molecular genetics
      findings obtained by DNA sequencing.

PMID- 16439605
TI  - Determination of SMN1/SMN2 gene dosage by a quantitative genotyping platform
      combining capillary electrophoresis and MALDI-TOF mass spectrometry.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is a common inherited and fatal
      neuromuscular disease caused by deletions and/or mutations that lead to altered
      concentrations of proteins encoded by the survival motor neuron genes SMN1 and
      SMN2. Because of the high incidence (at least 1 in 10,000 live births and a
      carrier frequency of 1 in 35 to 1 in 50) and severity of the disease, precise
      quantification of SMN1 and SMN2 gene copy numbers is essential for diagnosis and
      genetic counseling. METHODS: We developed a genotyping platform combining
      capillary electrophoresis and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) to quantify absolute gene dosage. The
      absolute gene dosage can be determined by a multiplexed competitive PCR protocol
      followed by capillary electrophoresis analysis. The relative SMN1/SMN2 ratio can
      be analyzed by PinPoint assay followed by MALDI-TOF MS analysis. RESULTS: The
      complementary assays were evaluated in confirmed cases including 9 affected
      patients, 33 carriers, and 478 healthy individuals from the general population.
      We were able to determine all genotypes with different SMN1/SMN2 gene copy number
      ratios, which unambiguously diagnosed carrier status and the severity of SMA with
      100% specificity. CONCLUSIONS: This quantitative genotyping platform is suitable
      for detection of SMA. The described approach may serve as a general quantitative
      genotyping method for molecular diagnosis of other inheritable diseases.

PMID- 16439606
TI  - Determination of cyanide in blood by isotope-dilution gas chromatography-mass
      spectrometry.
AB  - BACKGROUND: Cyanide (CN) is a lethal toxin. Quantification in blood is necessary
      to indicate exposure from many sources, including food, combustion byproducts,
      and terrorist activity. We describe an automated procedure based on isotope
      dilution gas chromatography-mass spectrometry (ID GC/MS) for the accurate and
      rapid determination of CN in whole blood. METHODS: A known amount of isotopically
      labeled potassium cyanide (K13C15N) was added to 0.5 g of whole blood in a
      headspace vial. Hydrogen cyanide was generated through the addition of phosphoric
      acid, and after a 5-min incubation, 0.5 mL of the headspace was injected into the
      GC/MS at an oven temperature of -15 degrees C. The peak areas from the sample,
      1H12C14N+, at m/z 27, and the internal standard, 1H13C15N+, at m/z 29, were
      measured, and the CN concentration was quantified by ID. The analysis time was 15
      min for a single injection. RESULTS: We demonstrated method accuracy by measuring
      the CN content of unfrozen whole blood samples fortified with a known amount of
      CN. Intermediate precision was demonstrated by periodic analyses over a 14-month
      span. Relative expanded uncertainties based on a 95% level of confidence with a
      coverage factor of 2 at CN concentrations of 0.06, 0.6, and 1.5 microg/g were
      8.3%, 5.4%, and 5.3%, respectively. The mean deviation from the known value for
      all concentrations was <4%. CONCLUSION: The automated ID GC/MS method can
      accurately and rapidly quantify nanogram per gram to microgram per gram
      concentrations of CN in blood.

PMID- 16439607
TI  - Effect of sex and assay method on serum concentrations of growth hormone in
      patients with acromegaly and in healthy controls.
AB  - BACKGROUND: Diagnosis and follow-up of acromegaly is based on measurements of
      serum growth hormone (GH) concentrations during an oral glucose tolerance test
      (OGTT). A nadir value <1 microg/L is commonly used to define a normal response,
      but some authors suggest lower cutoff values. METHODS: To compare the results and
      subsequent patient classification obtained with 3 GH assays, we obtained basal
      serum samples from 78 apparently healthy adult controls (43 women and 35 men;
      median age, 32.5 years) and from 71 treated (44 women and 27 men; median age,
      55.2 years) and 7 untreated acromegaly patients (4 women and 3 men; median age,
      54.6 years), and OGTT was performed on all patients and on 72 of the 78 controls.
      GH was determined by 2 immunometric assays-a double monoclonal (AutoDELFIA;
      Wallac) and a monopolyclonal (Immulite 2000; DPC) assay-and in a limited set of
      samples by an RIA (Spectria RIA; Orion). RESULTS: There was a strong correlation
      (r = 0.995; P < 0.001) between the 2 immunometric methods, but the results
      obtained with the Immulite 2000 were, on average, 1.4-fold higher than those
      obtained with the AutoDELFIA. At concentrations around the cutoff (1 microg/L),
      however, the difference was approximately 2-fold. Overall, the Orion RIA method
      also showed a good correlation (r = 0.951-0.959) with the other methods, but it
      did not measure concentrations <2 microg/L. Women had higher basal and OGTT nadir
      GH concentrations than men. CONCLUSION: Reference intervals should be determined
      separately for each method, and the need for establishing sex-specific reference
      values should be investigated.

PMID- 16439608
TI  - Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric
      quantification of succinylacetone.
AB  - BACKGROUND: False-positive and false-negative results occur in current newborn
      screening programs for hepatorenal tyrosinemia, which measure tyrosine
      concentrations in blood spots, sometimes in combination with other metabolites,
      including succinylacetone. We present our experience with a newly described
      method for succinylacetone quantification in routine newborn screening. METHODS:
      Succinylacetone was extracted from blood spots that had already been extracted
      with absolute methanol for acylcarnitine and amino acid analysis. The solvent was
      acetonitrile-water (80:20 by volume) containing formic acid, hydrazine hydrate,
      and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was
      performed by tandem mass spectrometry in a separate run. RESULTS: Of 61,344
      samples, 99.6% had succinylacetone concentrations < or =5 micromol/L. With a
      cutoff of 10 micromol/L, no false-positive results were obtained. In 2 patients,
      the succinylacetone concentrations in the dried blood spots from the 36th and
      56th hours of life were 152 and 271 micromol/L, respectively, and the tyrosine
      concentrations were 54 and 129 micromol/L. Hepatorenal tyrosinemia was
      subsequently confirmed in both patients. Retrospective analysis of the neonatal
      screening samples of 2 additional known patients revealed increased
      succinylacetone concentrations of 46 and 169 micromol/L, respectively.
      CONCLUSIONS: Tandem mass spectrometric quantification directly from residual
      blood spots is a useful method for the early detection of hepatorenal tyrosinemia
      in newborn-screening programs.

PMID- 16439610
TI  - P-selectin- and CD63-exposing platelet microparticles reflect platelet activation
      in peripheral arterial disease and myocardial infarction.
AB  - BACKGROUND: Platelet-derived microparticles (PMPs) are generally considered a
      marker of platelet activation in cardiovascular disease. We studied the extent to
      which PMP subpopulations parallel platelet activation in vitro and in vivo.
      METHODS: Using flow cytometry, we analyzed PMP subpopulations from resting and
      activated platelets in vitro (n = 6) as well as from plasma samples of patients
      with stable angina, peripheral arterial disease, or myocardial infarction [non-ST
      elevation (NSTEMI) and ST-elevation (STEMI)] and from older, age- and sex-matched
      and young healthy individuals [n = 10 for all groups except NSTEMI (n = 11)].
      Coagulation markers prothrombin fragment F(1 + 2) and thrombin-antithrombin
      complexes were determined by ELISA. The PMP-associated fraction of soluble (s)P
      selectin was estimated by ELISA. RESULTS: In vitro, stimulation of platelets with
      thrombin receptor-activating peptide (15 micromol/L) or the calcium ionophore
      A23187 (2.5 micromol/L) increased fractions of both platelets and PMPs exposing P
      selectin or CD63 (P <0.001 for all). Whereas the number of PMPs released by
      A23187-stimulated platelets increased significantly (P <0.001), the number of
      PMPs released from thrombin receptor-activating peptide-stimulated platelets
      remained constant (P >0.05). Ex vivo, numbers of circulating PMPs were comparable
      in all groups. Compared with young persons, P-selectin-exposing PMPs were
      increased in older persons (P = 0.02) and were further increased in patients with
      NSTEMI (P = 0.007) and STEMI (P = 0.045). CD63-exposing PMPs were increased in
      patients with peripheral arterial disease (P = 0.041), NSTEMI (P = 0.001), and
      STEMI (P = 0.049). Subpopulations exposing P-selectin or CD63 correlated with
      each other (r = 0.581; P <0.001), but neither correlated with the plasma
      concentrations of F(1 + 2) or thrombin-antithrombin complexes. The PMP-associated
      fraction of sP-selectin constituted only 2.2 (4.7)% [mean (SD)] of total sP
      selectin. CONCLUSIONS: PMP subpopulations reflect platelet activation status
      better than the total number of PMPs. Increased concentrations of circulating PMP
      subpopulations are found in aging, and further increases are encountered in
      peripheral arterial disease and myocardial infarction.

PMID- 16439611
TI  - Identification of various allosteric interaction sites on M1 muscarinic receptor
      using 125I-Met35-oxidized muscarinic toxin 7.
AB  - Monoiodinated, Met35-oxidized muscarinic toxin 7 (MT7ox) was synthesized, and its
      affinity constants for free or N-methyl scopolamine (NMS)-occupied hM1 receptor
      were measured directly by equilibrium and kinetic binding experiments. Identical
      values were obtained with the two types of assay methods, 14 pM and 0.9 nM in
      free or NMS-liganded receptor states, respectively, highlighting a strong
      negative cooperativity between this allosteric toxin and NMS. Identical results
      were obtained with indirect binding experiments with [3H]NMS using the ternary
      complex model, clearly demonstrating the reciprocal nature of this cooperativity.
      Furthermore, the effects of various orthosteric and allosteric agents on the
      dissociation kinetic of 125I-MT7ox were measured and show that, except for the
      MT1 toxin, all of the ligands studied [NMS, atropine, gallamine, brucine,
      tacrine, staurosporine, and (9S,10S,12R)-2,3,9,10,11-hexahydro-10-hydroxy-9
      methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4
      i][1,6]benzodiazocine-10-carboxylic acid hexyl ester (KT5720)] interact
      allosterically with muscarinic toxin 7. Equilibrium binding experiments with 125I
      MT7ox and [3H]NMS were conducted to reveal the effects of these ligands on the
      free receptor, and affinity constants (pKx values) were calculated using the
      allosteric ternary complex model. Our results suggest that MT7 toxin interacts
      with hM1 receptor at a specific allosteric site, which may partially overlap
      those identified previously for "classic" or "atypical" allosteric agents and
      highlight the potential of this new allosteric tracer in studying allosterism at
      muscarinic receptors.

PMID- 16439609
TI  - Single-nucleotide polymorphisms for diagnosis of salt-sensitive hypertension.
AB  - BACKGROUND: Salt-sensitive (SS) hypertension affects >30 million Americans and is
      often associated with low plasma renin activity. We tested the diagnostic
      validity of several candidate genes for SS and low-renin hypertension. METHODS:
      In Japanese patients with newly diagnosed, untreated hypertension (n = 184), we
      studied polymorphisms in 10 genes, including G protein-coupled receptor kinase
      type 4 (GRK4), some variations of which are associated with hypertension and
      impair D1 receptor (D1R)-inhibited renal sodium transport. We used the
      multifactor dimensionality reduction method to determine the genotype associated
      with salt sensitivity (> or =10% increase in blood pressure with high sodium
      intake) or low renin. To determine whether the GRK4 genotype is associated with
      impaired D1R function, we tested the natriuretic effect of docarpamine, a
      dopamine prodrug, in normotensive individuals with or without GRK4 polymorphisms
      (n = 18). RESULTS: A genetic model based on GRK4 R65L, GRK4 A142V, and GRK4 A486V
      was 94.4% predictive of SS hypertension, whereas the single-locus model with only
      GRK4 A142V was 78.4% predictive, and a 2-locus model of GRK4 A142V and CYP11B2 C
      344T was 77.8% predictive of low-renin hypertension. Sodium excretion was
      inversely related to the number of GRK4 variants in hypertensive persons, and the
      natriuretic response to dopaminergic stimulation was impaired in normotensive
      persons having > or =3 GRK4 gene variants. CONCLUSIONS: GRK4 gene variants are
      associated with SS and low-renin hypertension. However, the genetic model
      predicting SS hypertension is different from the model for low renin, suggesting
      genetic differences in these 2 phenotypes. Like low-renin testing, screening for
      GRK4 variants may be a useful diagnostic adjunct for detection of SS
      hypertension.

PMID- 16439612
TI  - Iron released by sodium nitroprusside contributes to heme oxygenase-1 induction
      via the cAMP-protein kinase A-mitogen-activated protein kinase pathway in RAW
      264.7 cells.
AB  - Nitric oxide (NO) is a potent inducer of heme oxygenase (HO)-1, and NO-induced HO
      1 expression is dependent on the cGMP-signaling pathway. Sodium nitroprusside
      (SNP) produces NO and iron. However, it is unclear whether NO is exclusively
      responsible for induction of HO-1 by SNP in RAW 264.7 cells. We tested our
      hypothesis that iron may contribute more to the SNP induction of HO-1 than does
      NO by comparing the HO-1 protein level and the production of NO in RAW 264.7
      cells treated with SNP and S-nitroso-N-acetyl-DL-penicillamine (SNAP). Although
      SNP induced less NO production than SNAP, SNP induced the production of more HO-1
      protein than did SNAP. Deferoxamine (DFO) decreased SNP- but not SNAP-induced HO
      1 expression but did not decrease the production of NO. SNP-induced HO-1 was
      significantly inhibited by specific protein kinase A (PKA) inhibitors or an
      antagonist of cAMP but not by guanylyl cyclase inhibitors. Exogenous iron (ferric
      ammonium citrate or ferricyanide) and forskolin increased the level of HO-1,
      which was inhibited by PKA inhibitor N-[2-(4-bromocinnamylamino)ethyl]-5
      isoquinoline (H89). These results indicate that iron and cAMP, but not cGMP, play
      crucial roles in the induction of HO-1 in RAW 264.7 cells. Moreover, DFO and
      inhibitors of extracellular signal-related kinases 1/2 or c-Jun NH(2)-terminal
      kinase inhibited HO-1 production induced by SNP. This study illustrates that iron
      rather than NO from SNP contributes to HO-1 induction. Therefore, studies on the
      effects of SNP should consider the role of iron in some biological functions. We
      concluded that iron released by SNP contributes to HO-1 induction via the cAMP
      PKA-mitogen-activated protein kinase pathway.

PMID- 16439613
TI  - Cell culture medium composition and translational adult bone marrow-derived stem
      cell research.
AB  - The use of fetal calf serum (FCS) for the culture of cells to be used in clinical
      trials raises potential hazards that cannot be neglected, but this is a
      regulatory issue. However, as specifically regards the isolation and expansion of
      human mesenchymal stem cells (MSCs), unfortunately serum-free media have not yet
      been defined. The alternative of using autologous serum is feasible only for the
      minority of clinical protocols involving low numbers of MSCs, because a minimum
      concentration of 10% in the culture medium is required. Besides, because
      allogeneic serum results in MSC growth arrest and death, use of pooled human
      serum does not represent an alternative. Finally, vast numbers of MSCs cultured
      in FCS-containing media have already been used in many clinical trials targeting
      a variety of disorders, without any significant side effects, including
      ventricular arrhythmia.

PMID- 16439614
TI  - Angiogenesis facilitated by autologous whole bone marrow stem cell
      transplantation for Buerger's disease.
AB  - We hypothesized that angiogenesis can be triggered by autologous whole bone
      marrow stem cell transplantation. Twenty-seven patients (34 lower limbs) with
      Buerger's disease, who were not candidates for surgical revascularization or
      radiologic intervention, were enrolled in this study. Six sites of the tibia bone
      were fenestrated using a 2.5-mm-diameter screw under fluoroscopic guidance.
      Clinical status and outcome were determined using the "Recommended Standards for
      Reports." To mobilize endothelial progenitor cells (EPCs) from bone marrow,
      recombinant human granulocyte colony-stimulating factor (r-HuG-CSF) was injected
      subcutaneously as a dose of 75 microg, preoperatively. During the follow-up
      period (19.1 +/- 3.5 months), one limb showed a markedly improved outcome (+3),
      and 26 limbs showed a moderately improved outcome (+2). Thirteen limbs among 17
      limbs with nonhealing ulcers healed. Postoperative angiograms were obtained for
      22 limbs. Two limbs showed marked (+3), five limbs moderate (+2), and nine limbs
      slight (+1) collateral development. However, six limbs showed no collateral
      development (0). Peripheral blood and bone marrow samples were analyzed for CD34
      and CD133 molecules to enumerate potential EPCs, and EPC numbers were found to be
      increased in peripheral blood and in bone marrow after r-HuG-CSF injection. In
      conclusion, the transplantation of autologous whole BMCs by fenestration of the
      tibia bone represents a simple, safe, and effective means of inducing therapeutic
      angiogenesis in patients with Buerger's disease.

PMID- 16439615
TI  - Use of differentiating adult stem cells (marrow stromal cells) to identify new
      downstream target genes for transcription factors.
AB  - We developed a strategy for use of microarray data to rapidly identify new
      downstream targets of transcription factors known to drive differentiation by
      following the time courses of gene expression as a relatively homogeneous
      population of stem/progenitor cells are differentiated to multiple phenotypes.
      Microarray assays were used to follow the differentiation of human marrow stromal
      cells (MSCs) into chondrocytes or adipocytes in three different experimental
      conditions. The steps of the analysis were the following: (a) hierarchical
      clustering was used to define groups of similarly behaving genes in each
      experiment, (b) candidates for new downstream targets of transcription factors
      that drive differentiation were then identified as genes that were consistently
      co-expressed with known downstream target genes of the transcription factors, and
      (c) the list of candidate new target genes was refined by identifying genes whose
      signal intensities showed a highly significant linear regression with the signal
      intensities of the known targets in all the data sets. Analysis of the data
      identified multiple new candidates for downstream targets for SOX9, SOX5,
      CCAAT/enhancer binding protein (C/EBP)-alpha, and peroxisome proliferator
      activated receptor (PPAR)-gamma. To validate the analysis, we demonstrated that
      PPAR-gamma protein specifically bound to the promoters of four new targets
      identified in the analyses. The same multistep analysis can be used to identify
      new downstream targets of transcription factors in other systems. Also, the same
      analysis should make it possible to use MSCs from bone marrow to define new
      mutations that alter chondogenesis or adipogenesis in patients with a variety of
      syndromes.

PMID- 16439616
TI  - Metabolic changes in mesenchymal stem cells in osteogenic medium measured by
      autofluorescence spectroscopy.
AB  - The purpose of this study was to measure metabolic changes in mesenchymal stem
      cells (MSCs) placed in osteogenic medium by autofluorescence spectroscopy. MSCs
      were plated in stem cell-supporting or osteogenic medium and imaged. Shift from
      the basic growth environment to the inductive osteogenic environment was
      confirmed by reverse transcription-polymerase chain reaction. Reduced pyridine
      nucleotides were detected by exciting near 366 nm and measuring fluorescence at
      450 nm, and oxidized flavoproteins were detected by exciting at 460 nm and
      measuring fluorescence at 540 nm. The ratio of these fluorescence measurements,
      reduction-oxidation (redox) fluorometry, is a noninvasive measure of the cellular
      metabolic state. The detected pyridine nucleotide to flavoprotein ratio decreased
      upon transitioning from the stem cell to the differentiated state, as well as
      with increasing cell density and cell-cell contact. MSC metabolism increased upon
      placement in differentiating medium and with increasing cell density and contact.
      Redox fluorometry is a feasible, noninvasive technique for distinguishing MSCs
      from further differentiated cells.

PMID- 16439617
TI  - The antiproliferative drug doxorubicin inhibits liver fibrosis in bile duct
      ligated rats and can be selectively delivered to hepatic stellate cells in vivo.
AB  - Hepatic stellate cell (HSC) proliferation is a key event in liver fibrosis;
      therefore, pharmacological intervention with antiproliferative drugs may result
      in antifibrotic effects. In this article, the antiproliferative effect of three
      cytostatic drugs was tested in cultured rat HSC. Subsequently, the antifibrotic
      potential of the most potent drug was evaluated in vivo. As a strategy to
      overcome drug-related toxicity, we additionally studied how to deliver this drug
      specifically to HSC by conjugating it to the HSC-selective drug carrier mannose-6
      phosphate-modified human serum albumin (M6PHSA). We investigated the effect of
      cisplatin, chlorambucil, and doxorubicin (DOX) on 5-bromo-2'-deoxyuridine
      incorporation in cultured HSC and found DOX to be the most potent drug. Treatment
      of bile duct-ligated (BDL) rats with daily i.v. injections of 0.35 mg/kg DOX from
      day 3 to 10 after BDL reduced alpha-smooth muscle actin-stained area in liver
      sections from 8.5 +/- 0.8 to 5.1 +/- 0.9% (P < 0.01) and collagen-stained area
      from 13.1 +/- 1.3 to 8.9 +/- 1.5% (P < 0.05). DOX was coupled to M6PHSA, and the
      organ distribution of this construct (M6PHSA-DOX) was investigated. Twenty
      minutes after i.v. administration, 50 +/- 6% of the dose was present in the
      livers, and colocalization of M6PHSA-DOX with HSC markers was observed. In
      addition, in vitro studies showed selective binding of M6PHSA-DOX to activated
      HSC. Moreover, M6PHSA-DOX strongly attenuated HSC proliferation in vitro,
      indicating that active drug is released after uptake of the conjugate. DOX
      inhibits liver fibrosis in BDL rats, and HSC-selective targeting of this drug is
      possible. This may offer perspectives for the application of antiproliferative
      drugs for antifibrotic purposes.

PMID- 16439618
TI  - Characterization of P-glycoprotein inhibition by major cannabinoids from
      marijuana.
AB  - The ATP-dependent drug efflux transporter P-glycoprotein (P-gp) plays a
      significant role in the absorption and disposition of many compounds. The purpose
      of this study was to investigate the possible interaction of P-gp with each of
      four major marijuana constituents: Delta(9)-tetrahydrocannabinol (THC), 11-nor
      Delta(9)-tetrahydrocannabinol-carboxylic acid (THC-COOH), cannabinol (CBN), and
      cannabidiol (CBD). The results of a P-gp ATPase activity screen showed that THC
      COOH, CBN, THC, and CBD all stimulated P-gp ATPase activity with a Michaelis
      Menten parameter (V(max)/K(m)) value of 1.3, 0.7, 0.1, and 0.05, respectively.
      Furthermore, CBD showed a concentration-dependent inhibitory effect on verapamil
      stimulated ATPase activity with an IC(50) value of 39.6 microM, whereas all other
      tested cannabinoids did not display appreciable inhibitory effects. Thus, the
      inhibitory effects of CBD on P-gp transport were further studied. At
      concentrations ranging from 5 to 100 microM, CBD robustly enhanced the
      intracellular accumulation of known P-gp substrates rhodamine 123 and doxorubicin
      in a concentration-dependent manner in Caco-2 and LLC-PK1/MDR1 cells. An IC(50)
      value of 8.44 microM was obtained for inhibition of P-gp function in LLC-PK1/MDR1
      cells as determined by flow cytometry using rhodamine 123 as a fluorescence
      probe. Following exposure to 30 microM CBD, the apparent permeability coefficient
      of rhodamine 123 across Caco-2 and rat brain microvessel endothelial cell
      monolayers was increased to 2.2- and 2.6-fold in the apical-to-basolateral
      direction but decreased to 0.69- and 0.47-fold in the basolateral-to-apical
      direction, respectively. These findings indicate that CBD significantly inhibits
      P-gp-mediated drug transport, suggesting CBD could potentially influence the
      absorption and disposition of other coadministered compounds that are P-gp
      substrates.

PMID- 16439619
TI  - Polysurgery of cell sheet grafts overcomes diffusion limits to produce thick,
      vascularized myocardial tissues.
AB  - Recently, the field of tissue engineering has progressed rapidly, but poor
      vascularization remains a major obstacle in bioengineering cell-dense tissues,
      limiting the viable size of constructs due to hypoxia, nutrient insufficiency,
      and waste accumulation. Therefore, new technologies for fabricating functional
      tissues with a well-organized vasculature are required. In the present study,
      neonatal rat cardiomyocytes were harvested as intact sheets from temperature
      responsive culture dishes and stacked into cell-dense myocardial tissues.
      However, the thickness limit for layered cell sheets in subcutaneous tissue was
      approximately 80 microm (3 layers). To overcome this limitation, repeated
      transplantation of triple-layer grafts was performed at 1, 2, or 3 day intervals.
      The two overlaid grafts completely synchronized and the whole tissues survived
      without necrosis in the 1 or 2 day interval cases. Multistep transplantation also
      created approximately 1 mm thick myocardium with a well-organized microvascular
      network. Furthermore, functional multilayer grafts fabricated over a surgically
      connectable artery and vein revealed complete graft perfusion via the vessels and
      ectopic transplantation of the grafts was successfully performed using direct
      vessel anastomoses. These cultured cell sheet integration methods overcome long
      standing barriers to producing thick, vascularized tissues, revealing a possible
      solution for the clinical repair of various damaged organs, including the
      impaired myocardium.

PMID- 16439621
TI  - Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous
      syndrome.
AB  - Cardio-facio-cutaneous (CFC) syndrome is a sporadic developmental disorder
      involving characteristic craniofacial features, cardiac defects, ectodermal
      abnormalities, and developmental delay. We demonstrate that heterogeneous de novo
      missense mutations in three genes within the mitogen-activated protein kinase
      (MAPK) pathway cause CFC syndrome. The majority of cases (18 out of 23) are
      caused by mutations in BRAF, a gene frequently mutated in cancer. Of the 11
      mutations identified, two result in amino acid substitutions that occur in
      tumors, but most are unique and suggest previously unknown mechanisms of B-Raf
      activation. Furthermore, three of five individuals without BRAF mutations had
      missense mutations in either MEK1 or MEK2, downstream effectors of B-Raf. Our
      findings highlight the involvement of the MAPK pathway in human development and
      will provide a molecular diagnosis of CFC syndrome.

PMID- 16439622
TI  - Prions in skeletal muscles of deer with chronic wasting disease.
AB  - The emergence of chronic wasting disease (CWD) in deer and elk in an increasingly
      wide geographic area, as well as the interspecies transmission of bovine
      spongiform encephalopathy to humans in the form of variant Creutzfeldt Jakob
      disease, have raised concerns about the zoonotic potential of CWD. Because meat
      consumption is the most likely means of exposure, it is important to determine
      whether skeletal muscle of diseased cervids contains prion infectivity. Here
      bioassays in transgenic mice expressing cervid prion protein revealed the
      presence of infectious prions in skeletal muscles of CWD-infected deer,
      demonstrating that humans consuming or handling meat from CWD-infected deer are
      at risk to prion exposure.

PMID- 16439623
TI  - A molecular jump mechanism of water reorientation.
AB  - Despite long study, a molecular picture of the mechanism of water reorientation
      is still lacking. Using numerical simulations, we find support for a pathway in
      which the rotating water molecule breaks a hydrogen bond (H-bond) with an
      overcoordinated first-shell neighbor to form an H-bond with an undercoordinated
      second-shell neighbor. The H-bond cleavage and the molecular reorientation occur
      concertedly and not successively as usually considered. This water reorientation
      mechanism involves large-amplitude angular jumps, rather than the commonly
      accepted sequence of small diffusive steps, and therefore calls for
      reinterpretation of many experimental data wherein water rotational relaxation is
      assumed to be diffusive.

PMID- 16439624
TI  - Getting serious about biofuels.

PMID- 16439625
TI  - Scientific misconduct. Fraud upends oral cancer field, casting doubt on
      prevention trial.

PMID- 16439627
TI  - Graduate training. U.S. beckons foreigners with science Fulbrights.

PMID- 16439626
TI  - Professional practice. Scientists keep some data to themselves.

PMID- 16439628
TI  - Quantum physics. Measurement schemes let physicists tiptoe through the quanta.

PMID- 16439629
TI  - Ecology. Rare tree species thrive in local neighborhoods.

PMID- 16439630
TI  - Chemistry. Walk on the wild side yields supersensitive chemical measurements.

PMID- 16439631
TI  - Extrasolar planets. I spy...a cold, little planet.

PMID- 16439620
TI  - Large-scale sequence analysis of avian influenza isolates.
AB  - The spread of H5N1 avian influenza viruses (AIVs) from China to Europe has raised
      global concern about their potential to infect humans and cause a pandemic. In
      spite of their substantial threat to human health, remarkably little AIV whole
      genome information is available. We report here a preliminary analysis of the
      first large-scale sequencing of AIVs, including 2196 AIV genes and 169 complete
      genomes. We combine this new information with public AIV data to identify new
      gene alleles, persistent genotypes, compensatory mutations, and a potential
      virulence determinant.

PMID- 16439632
TI  - Illegal drugs. U.K. backs off reclassifying cannabis as a dangerous drug.

PMID- 16439633
TI  - Japan-China dispute. Researchers caught between atoll and a hard place.

PMID- 16439634
TI  - Avian influenza. Donors draw plans to disburse $2 billion war chest for bird flu.

PMID- 16439635
TI  - Genetics. Biobank ties cancer genes to rare developmental syndrome.

PMID- 16439636
TI  - Virology. Genomic analysis hints at H5N1 pathogenicity.

PMID- 16439637
TI  - Mental health in developing countries. The unseen: mental illness's global toll.

PMID- 16439638
TI  - Mental health in developing countries. Mapping mental illness: an uncertain
      topography.

PMID- 16439639
TI  - Mental health in developing countries. China: healing the metaphorical heart.

PMID- 16439640
TI  - Mental health in developing countries. A spoonful of medicine--and a steady diet
      of normality.

PMID- 16439644
TI  - Where next for genome sequencing?

PMID- 16439646
TI  - Avoiding climate change.

PMID- 16439645
TI  - Thinking about NASA's future.

PMID- 16439647
TI  - Comment on "Reconstructing the origin of Andaman islanders".
AB  - On the basis of mitochondrial DNA sequence analyses, Thangaraj et al. (Brevia, 13
      May 2005, p. 996) proposed that Andaman islanders descended from the first humans
      to migrate out of Africa. We identified mitochondrial DNA from two northeast
      Indian Rajbanshi individuals that shares three specific mutations with the M31a
      lineage observed in the Great Andamanese, which suggests that the predecessor of
      haplogroup M31 originated on the Indian subcontinent.

PMID- 16439648
TI  - Professional skills. The merits of training mentors.

PMID- 16439649
TI  - Biochemistry. Loop grafting and the origins of enzyme species.

PMID- 16439650
TI  - Atmosphere. Climate change and human evolution.

PMID- 16439651
TI  - Geochemistry. Rising mountain ranges.

PMID- 16439652
TI  - Materials science. Making better ceramic composites with ice.

PMID- 16439653
TI  - Ecology. Staying connected in a turbulent world.

PMID- 16439654
TI  - The path forward for biofuels and biomaterials.
AB  - Biomass represents an abundant carbon-neutral renewable resource for the
      production of bioenergy and biomaterials, and its enhanced use would address
      several societal needs. Advances in genetics, biotechnology, process chemistry,
      and engineering are leading to a new manufacturing concept for converting
      renewable biomass to valuable fuels and products, generally referred to as the
      biorefinery. The integration of agroenergy crops and biorefinery manufacturing
      technologies offers the potential for the development of sustainable biopower and
      biomaterials that will lead to a new manufacturing paradigm.

PMID- 16439656
TI  - Ethanol can contribute to energy and environmental goals.
AB  - To study the potential effects of increased biofuel use, we evaluated six
      representative analyses of fuel ethanol. Studies that reported negative net
      energy incorrectly ignored coproducts and used some obsolete data. All studies
      indicated that current corn ethanol technologies are much less petroleum
      intensive than gasoline but have greenhouse gas emissions similar to those of
      gasoline. However, many important environmental effects of biofuel production are
      poorly understood. New metrics that measure specific resource inputs are
      developed, but further research into environmental metrics is needed.
      Nonetheless, it is already clear that large-scale use of ethanol for fuel will
      almost certainly require cellulosic technology.

PMID- 16439657
TI  - Optical detection of DNA conformational polymorphism on single-walled carbon
      nanotubes.
AB  - The transition of DNA secondary structure from an analogous B to Z conformation
      modulates the dielectric environment of the single-walled carbon nanotube (SWNT)
      around which it is adsorbed. The SWNT band-gap fluorescence undergoes a red shift
      when an encapsulating 30-nucleotide oligomer is exposed to counter ions that
      screen the charged backbone. The transition is thermodynamically identical for
      DNA on and off the nanotube, except that the propagation length of the former is
      shorter by five-sixths. The magnitude of the energy shift is described by using
      an effective medium model and the DNA geometry on the nanotube sidewall. We
      demonstrate the detection of the B-Z change in whole blood, tissue, and from
      within living mammalian cells.

PMID- 16439658
TI  - Rapid uplift of the Altiplano revealed through 13C-18O bonds in paleosol
      carbonates.
AB  - The elevation of Earth's surface is among the most difficult environmental
      variables to reconstruct from the geological record. Here we describe an approach
      to paleoaltimetry based on independent and simultaneous determinations of soil
      temperatures and the oxygen isotope compositions of soil waters, constrained by
      measurements of abundances of 13C-18O bonds in soil carbonates. We use this
      approach to show that the Altiplano plateau in the Bolivian Andes rose at an
      average rate of 1.03 +/- 0.12 millimeters per year between approximately 10.3 and
      approximately 6.7 million years ago. This rate is consistent with the removal of
      dense lower crust and/or lithospheric mantle as the cause of elevation gain.

PMID- 16439659
TI  - Freezing as a path to build complex composites.
AB  - Materials that are strong, ultralightweight, and tough are in demand for a range
      of applications, requiring architectures and components carefully designed from
      the micrometer down to the nanometer scale. Nacre, a structure found in many
      molluscan shells, and bone are frequently used as examples for how nature
      achieves this through hybrid organic-inorganic composites. Unfortunately, it has
      proven extremely difficult to transcribe nacre-like clever designs into synthetic
      materials, partly because their intricate structures need to be replicated at
      several length scales. We demonstrate how the physics of ice formation can be
      used to develop sophisticated porous and layered-hybrid materials, including
      artificial bone, ceramic-metal composites, and porous scaffolds for osseous
      tissue regeneration with strengths up to four times higher than those of
      materials currently used for implantation.

PMID- 16439660
TI  - The cellular basis of a corollary discharge.
AB  - How do animals discriminate self-generated from external stimuli during behavior
      and prevent desensitization of their sensory pathways? A fundamental concept in
      neuroscience states that neural signals, termed corollary discharges or efference
      copies, are forwarded from motor to sensory areas. Neurons mediating these
      signals have proved difficult to identify. We show that a single, multisegmental
      interneuron is responsible for the pre- and postsynaptic inhibition of auditory
      neurons in singing crickets (Gryllus bimaculatus). Therefore, this neuron
      represents a corollary discharge interneuron that provides a neuronal basis for
      the central control of sensory responses.

PMID- 16439661
TI  - Nonrandom processes maintain diversity in tropical forests.
AB  - An ecological community's species diversity tends to erode through time as a
      result of stochastic extinction, competitive exclusion, and unstable host-enemy
      dynamics. This erosion of diversity can be prevented over the short term if
      recruits are highly diverse as a result of preferential recruitment of rare
      species or, alternatively, if rare species survive preferentially, which
      increases diversity as the ages of the individuals increase. Here, we present
      census data from seven New and Old World tropical forest dynamics plots that all
      show the latter pattern. Within local areas, the trees that survived were as a
      group more diverse than those that were recruited or those that died. The larger
      (and therefore on average older) survivors were more diverse within local areas
      than the smaller survivors. When species were rare in a local area, they had a
      higher survival rate than when they were common, resulting in enrichment for rare
      species and increasing diversity with age and size class in these complex
      ecosystems.

PMID- 16439655
TI  - Community genomics among stratified microbial assemblages in the ocean's
      interior.
AB  - Microbial life predominates in the ocean, yet little is known about its genomic
      variability, especially along the depth continuum. We report here genomic
      analyses of planktonic microbial communities in the North Pacific Subtropical
      Gyre, from the ocean's surface to near-sea floor depths. Sequence variation in
      microbial community genes reflected vertical zonation of taxonomic groups,
      functional gene repertoires, and metabolic potential. The distributional patterns
      of microbial genes suggested depth-variable community trends in carbon and energy
      metabolism, attachment and motility, gene mobility, and host-viral interactions.
      Comparative genomic analyses of stratified microbial communities have the
      potential to provide significant insight into higher-order community organization
      and dynamics.

PMID- 16439662
TI  - An architectural framework that may lie at the core of the postsynaptic density.
AB  - The postsynaptic density (PSD) is a complex assembly of proteins associated with
      the postsynaptic membrane that organizes neurotransmitter receptors, signaling
      pathways, and regulatory elements within a cytoskeletal matrix. Here we show that
      the sterile alpha motif domain of rat Shank3/ProSAP2, a master scaffolding
      protein located deep within the PSD, can form large sheets composed of helical
      fibers stacked side by side. Zn2+, which is found in high concentrations in the
      PSD, binds tightly to Shank3 and may regulate assembly. Sheets of the Shank
      protein could form a platform for the construction of the PSD complex.

PMID- 16439663
TI  - Design and evolution of new catalytic activity with an existing protein scaffold.
AB  - The design of enzymes with new functions and properties has long been a goal in
      protein engineering. Here, we report a strategy to change the catalytic activity
      of an existing protein scaffold. This was achieved by simultaneous incorporation
      and adjustment of functional elements through insertion, deletion, and
      substitution of several active site loops, followed by point mutations to fine
      tune the activity. Using this approach, we were able to introduce beta-lactamase
      activity into the alphabeta/betaalpha metallohydrolase scaffold of glyoxalase II.
      The resulting enzyme, evMBL8 (evolved metallo beta-lactamase 8), completely lost
      its original activity and, instead, catalyzed the hydrolysis of cefotaxime with a
      (kcat/Km)app of 1.8 x 10(2) (mole/liter)(-1) second(-1), thus increasing
      resistance to Escherichia coli growth on cefotaxime by a factor of about 100.

PMID- 16439665
TI  - Vasa recta pericytes express a strong inward rectifier K+ conductance.
AB  - Strong inward rectifier potassium channels are expressed by some vascular smooth
      muscle cells and facilitate K+-induced hyperpolarization. Using whole cell patch
      clamp of isolated descending vasa recta (DVR), we tested whether strong inward
      rectifier K+ currents are present in smooth muscle and pericytes. Increasing
      extracellular K+ from 5 to 50 and 140 mmol/l induced inward rectifying currents.
      Those currents were Ba2+ sensitive and reversed at the K+ equilibrium potential
      imposed by the electrode and extracellular buffers. Ba2+ binding constants in
      symmetrical K+ varied between 0.24 and 24 micromol/l at -150 and -20 mV,
      respectively. Ba2+ blockade was time and voltage dependent. Extracellular Cs+
      also blocked the inward currents with binding constants between 268 and 4,938
      micromol/l at -150 and -50 mV, respectively. Ba2+ (30 micromol/l) and ouabain (1
      mmol/l) depolarized pericytes by an average of 11 and 24 mV, respectively.
      Elevation of extracellular K+ from 5 to 10 mmol/l hyperpolarized pericytes by 6
      mV. That hyperpolarization was reversed by Ba2+ (30 micromol/l). We conclude that
      strong inward rectifier K+ channels and Na+-K+-ATPase contribute to resting
      potential and that KIR channels can mediate K+-induced hyperpolarization of DVR
      pericytes.

PMID- 16439664
TI  - A virus reveals population structure and recent demographic history of its
      carnivore host.
AB  - Directly transmitted parasites often provide substantial information about the
      temporal and spatial characteristics of host-to-host contact. Here, we
      demonstrate that a fast-evolving virus (feline immunodeficiency virus, FIV) can
      reveal details of the contemporary population structure and recent demographic
      history of its natural wildlife host (Puma concolor) that were not apparent from
      host genetic data and would be impossible to obtain by other means. We suggest
      that rapidly evolving pathogens may provide a complementary tool for studying
      population dynamics of their hosts in "shallow" time.

PMID- 16439666
TI  - Brief exposure to exogenous testosterone increases death signaling and adversely
      affects myocardial function after ischemia.
AB  - Chronic endogenous testosterone exposure adversely affects proinflammatory and
      proapoptotic signaling after ischemia/reperfusion; however, it remains unknown
      whether a single acute testosterone exposure is equally detrimental. We
      hypothesized that acute exogenous testosterone infusion before ischemia would
      worsen myocardial functional recovery, increase the activation of MAPKs and
      caspase-3, and increase myocardial proinflammatory cytokine production. To study
      this, isolated-perfused rat hearts (Langendorff) from adult females and castrated
      males were subjected to 25-min ischemia and 40-min reperfusion with and without
      acute testosterone infusion (17beta-hydroxy-4-androstenone, 10 ng x ml(-1) x min(
      1)) before ischemia. Myocardial contractile function was continuously recorded.
      After ischemia/reperfusion, hearts were assessed for levels of testosterone
      (ELISA), expression of proinflammatory cytokines (ELISA), and activation of MAPKs
      and caspase-3 (Western blot analysis). Data were analyzed with two-way ANOVA or
      Student's t-test; P < 0.05 was statistically significant. All indices of
      postischemic functional recovery were decreased with acute exogenous testosterone
      compared with the untreated groups. Acute testosterone infusion increased
      activation of MAPKs and caspase-3 following ischemia/reperfusion. However, there
      were no significant differences in the myocardial proinflammatory cytokine
      production after brief testosterone infusion. A single acute exposure to
      exogenous testosterone before ischemia worsens myocardial functional recovery and
      increases activation of MAPKs and caspase-3. These findings confirm the
      deleterious effects of testosterone on myocardium, elucidate the nongenomic
      mechanistic pathways of testosterone, and may have important clinical
      implications for patients who have acute exposure to exogenous testosterone.

PMID- 16439668
TI  - Simultaneous exposure to ATP and phenylephrine induces a sustained elevation in
      the intracellular calcium concentration in supraoptic neurons.
AB  - Vasopressin (VP) release from the hypothalamo-neurohypophyseal system (HNS) is
      stimulated by ATP activation of P2X purinergic receptors and by activation of 1
      adrenergic receptors by phenylephrine (PE). These responses are potentiated by
      simultaneous exposure to ATP+PE. Potentiation was blocked by depleting
      intracellular calcium stores with thapsigargin. To test the hypothesis that the
      synergistic response to ATP+PE reflects alterations in the intracellular calcium
      concentration ([Ca2+]i), [Ca2+]i was monitored in supraoptic neurons in HNS
      explants loaded with fura 2-AM. Both ATP and PE induced rapid, but transient,
      elevations in [Ca2+]i. In 0.3 mM Ca2+, the peak response to ATP was greater than
      to PE but did not differ from the peak response to ATP+PE. A sustained elevation
      in [Ca2+]i was induced by ATP+PE, that was greater than ATP or PE alone. In 2 mM
      Ca2+, the peak response to ATP+PE was significantly greater than to either ATP or
      PE alone, and the sustained response to ATP+PE was greater than to either agent
      alone. Responses were comparable in the presence of TTX. The sustained elevation
      in [Ca2+]i was also observed when ATP+PE was removed after 1 min, but it was
      eliminated by either thapsigargin or removing external calcium, indicating that
      both calcium influx and calcium release from internal stores are required. Some
      cells were vasopressinergic based on a VP-induced increase in [Ca2+]i. These
      observations support the hypothesis that simultaneous exposure to ATP+PE induces
      a different pattern of [Ca2+]i than either agent alone that may initiate events
      leading to synergistic stimulation of VP release.

PMID- 16439667
TI  - Impact of state of arousal and stress neuropeptides on urodynamic function in
      freely moving rats.
AB  - Corticotropin-releasing factor (CRF) is a neurotransmitter in Barrington's
      nucleus neurons. These neurons can coregulate parasympathetic tone to the bladder
      (to modulate micturition) and brain noradrenergic activity (to affect arousal).
      To identify the role of CRF in the regulation of micturition, the effects of CRF
      agonists and antagonists on urodynamics in the unanesthetized rat were
      characterized. Rats were implanted with bladder and intrathecal or
      intraperitoneal catheters under isoflurane anesthesia. Cystometry was performed
      in the unanesthetized, unrestrained state at least 24 h later. In some cases,
      cortical electroencephalographic activity (EEG) was recorded simultaneously to
      assess arousal state. During cystometry, the state of arousal often shifted
      between waking and sleeping and urodynamic function changed depending on the
      state. Micturition threshold, bladder capacity, and micturition volume were all
      increased during sleep. The CRF1/CRF2 receptor agonists CRF and urocortin 2
      increased bladder capacity and micturition volume in awake but not in sleeping
      rats. Conversely, the CRF1 receptor antagonists antalarmin and NBI-30775
      increased urinary frequency and decreased bladder capacity in awake rats. The
      present results demonstrate a profound effect of the state of arousal on
      urodynamic function and suggest that simultaneous monitoring of EEG and
      cystometry may provide a useful model for studying nocturnal enuresis and other
      urinary disorders. In addition, the results provide evidence for an inhibitory
      influence of CRF in the spinal pathway on micturition. Targeting the CRF system
      in the spinal cord may provide a novel approach for treating urinary disorders.

PMID- 16439670
TI  - Temporal differences in bladder dysfunction caused by diabetes, diuresis, and
      treated diabetes in mice.
AB  - Diabetic bladder dysfunction is a common complication of diabetes mellitus (DM)
      with poorly understood natural history. This study examined the temporal changes
      in bladder function 3, 9, 12, and 20 wk after induction of DM by streptozotocin
      (STZ) in male C57BL/6 mice compared with that in age-matched diabetic mice
      treated with insulin, 5% sucrose-induced diuretic mice, and sham-treated control
      mice. Conscious cystometrograms of mice were examined in addition to the
      measurements of micturition cycle. Diabetes resulted in decreased body weight.
      Bladder weight, urine output, bladder capacity, and compliance increased in the
      DM and diuretic groups. Peak voiding pressure (PVP) increased initially in both
      DM and diuretic mice. However, in DM mice, PVP dropped dramatically at and after
      12 wk. Similar changes in the capacity, compliance, and emptying ability of the
      bladder were seen during the first 9 wk of the diabetes or diuresis, whereas
      significant decline in the emptying ability of the bladder was only seen in
      diabetes after 12 wk of disease in mice. Long-term insulin replacement
      effectively reversed most changes in bladder function. These results suggest that
      the transition from a compensated to a decompensated bladder dysfunction occurs 9
      12 wk after induction of DM in mice by STZ.

PMID- 16439671
TI  - Wavelength-dependent effects of evening light exposure on sleep architecture and
      sleep EEG power density in men.
AB  - Light strongly influences the circadian timing system in humans via non-image
      forming photoreceptors in the retinal ganglion cells. Their spectral sensitivity
      is highest in the short-wavelength range of the visible light spectrum as
      demonstrated by melatonin suppression, circadian phase shifting, acute
      physiological responses, and subjective alertness. We tested the impact of short
      wavelength light (460 nm) on sleep EEG power spectra and sleep architecture. We
      hypothesized that its acute action on sleep is similar in magnitude to reported
      effects for polychromatic light at higher intensities and stronger than longer
      wavelength light (550 nm). The sleep EEGs of eight young men were analyzed after
      2-h evening exposure to blue (460 nm) and green (550 nm) light of equal photon
      densities (2.8 x 10(13) photons x cm(-2) x s(-1)) and to dark (0 lux) under
      constant posture conditions. The time course of EEG slow-wave activity (SWA; 0.75
      4.5 Hz) across sleep cycles after blue light at 460 nm was changed such that SWA
      was slightly reduced in the first and significantly increased during the third
      sleep cycle in parietal and occipital brain regions. Moreover, blue light
      significantly shortened rapid eye movement (REM) sleep duration during these two
      sleep cycles. Thus the light effects on the dynamics of SWA and REM sleep
      durations were blue shifted relative to the three-cone visual photopic system
      probably mediated by the circadian, non-image-forming visual system. Our results
      can be interpreted in terms of an induction of a circadian phase delay and/or
      repercussions of a stronger alerting effect after blue light, persisting into the
      sleep episode.

PMID- 16439669
TI  - Esophageal-gastric relaxation reflex in rat: dual control of peripheral nitrergic
      and cholinergic transmission.
AB  - It has long been known that the esophageal distension produced by swallowing
      elicits a powerful proximal gastric relaxation. Gastroinhibitory control by the
      esophagus involves neural pathways from esophageal distension-sensitive neurons
      in the nucleus tractus solitarius centralis (cNTS) with connections to virtually
      all levels of the dorsal motor nucleus of the vagus (DMV). We have shown recently
      that cNTS responses are excitatory and primarily involve tyrosine hydroxylase
      immunoreactive cells, whereas the DMV response involves both an alpha1 excitatory
      and an alpha2 inhibitory response. In the present study, using an esophageal
      balloon distension to evoke gastric relaxation (esophageal-gastric reflex, EGR),
      we investigated the peripheral pharmacological basis responsible for this reflex.
      Systemic administration of atropine methyl nitrate reduced the amplitude of the
      gastric relaxation to 52.0+/-4.4% of the original EGR, whereas NG-nitro-L
      arginine methyl ester (L-NAME) reduced it to 26.3+/-7.2% of the original EGR.
      Concomitant administration of atropine methyl nitrate and L-NAME reduced the
      amplitude of the gastric relaxation to 4.0+/-2.5% of control. This reduction in
      the amplitude of induced EGR is quite comparable (4.3+/-2.6%) to that seen when
      the animal was pretreated with the nicotinic ganglionic blocker hexamethonium. In
      the presence of bethanechol, the amplitude of the esophageal distension-induced
      gastric relaxation was increased to 177.0+/-10.0% of control; administration of L
      NAME reduced this amplitude to 19.9+/-9.5%. Our data provide a clear
      demonstration that the gastroinhibitory control by the esophagus is mediated via
      a dual vagal innervation consisting of inhibitory nitrergic and excitatory
      cholinergic transmission.

PMID- 16439672
TI  - IGF-I and insulin receptor signal transduction in trout muscle cells.
AB  - In this study, primary cultures of trout skeletal muscle cells were used to
      investigate the main signal transduction pathways of insulin and IGF-I receptors
      in rainbow trout muscle. At different stages of in vitro development (myoblasts
      on day 1, myocytes on day 4, and fully developed myotubes on day 11), we detected
      in these cells the presence of immunoreactivity against ERK 1/2 MAPK and Akt/PKB
      proteins, components of the MAPK and the phosphatidylinositol 3-kinase-Akt
      pathways, respectively, two of the main intracellular transduction pathways for
      insulin and IGF-I receptors. Both insulin and IGF-I activated both pathways,
      although the latter provoked higher immunoreactivity of phosphorylated MAPKs and
      Akt proteins. At every stage, increases in total MAPK immunoreactivity levels
      were observed when cells were stimulated with IGF-I or insulin, while total Akt
      immunoreactivity levels changed little under stimulation of peptides. Total Akt
      and total MAPK levels increased as skeletal muscle cells differentiated in
      culture. Moreover, when cells were incubated with IGF-I or insulin, MAPK-P
      immunoreactivity levels showed greater increases over the basal levels on days 1
      and 4, with no effect observed on day 11. Although Akt-P immunoreactivity
      displayed improved responses on days 1 and 4 as well, a stimulatory effect was
      still observed on day 11. In addition, the present study demonstrates that
      purified trout insulin receptors possess higher phosphorylative activity per unit
      of receptor than IGF-I receptors. In conclusion, these results indicate that
      trout skeletal muscle culture is a suitable model to study the insulin and IGF-I
      signal transduction molecules and that there is a different regulation of MAPK
      and Akt pathways depending on the developmental stage of the muscle cells.

PMID- 16439673
TI  - Antidipsogenic effects of a TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate,
      injected into the cerebroventricle.
AB  - Transient receptor potential vanilloid 4 (TRPV4) is one member of the TRP
      superfamily of nonselective cation channels. Recently, the possibility has been
      raised that TRPV4 is an osmoreceptor, because it is found in the
      circumventricular organs where osmoreceptors are supposed to be distributed and
      because it is sensitive to osmotic pressure in in vitro experiments. In addition,
      TRPV4 knockout mice have abnormal osmosensitivity. In this study, effects of
      4alpha-phorbol 12,13-didecanoate (4alpha-PDD), a TRPV4 agonist, on drinking
      behavior were examined to investigate roles for TRPV4 as an osmoreceptor in vivo
      in wild-type animals. Intracerebroventricular injections of 4alpha-PDD inhibited
      water intake under normal conditions in both light and dark periods of the day,
      after food deprivation, and after administration of angiotensin II. However, this
      drug did not influence increased water intake after administration of a
      hypertonic solution or after water deprivation that significantly increased
      plasma osmolality. Locomotor activity of the 4alpha-PDD-injected group decreased
      slightly compared with that of the vehicle-injected group; however, sweet taste,
      food intake, and body temperature were not different between the two groups. The
      antidipsogenic effects of 4alpha-PDD were blocked by preinjection into the
      ventricle of TRPV4 antagonists such as ruthenium red or gadolinium. These
      findings suggest that TRPV4 regulates drinking behavior under certain conditions,
      and the regulation interacts with the angiotensin II pathway.

PMID- 16439674
TI  - Acute myeloid leukemia is associated with retroviral gene transfer to
      hematopoietic progenitor cells in a rhesus macaque.
AB  - We report, for the first time, a replication-defective retroviral vector
      associated neoplasia in a nonhuman primate. Five years after transplantation with
      CD34+ cells transduced with a retroviral vector expressing enhanced green
      fluorescent protein (eGFP) and a drug-resistant variant of the dihydrofolate
      reductase gene (L22Y), a rhesus macaque developed a fatal myeloid sarcoma, a type
      of acute myeloid leukemia. Tumor cells contained 2 clonal vector insertions. One
      insertion was found in BCL2-A1, an antiapoptotic gene. This event suggests that
      currently available retroviral vectors may have long-term side effects,
      particularly in hematopoietic stem and progenitor cells.

PMID- 16439675
TI  - Dual function for the adaptor MIST in IFN-gamma production by NK and CD4+NKT
      cells regulated by the Src kinase Fgr.
AB  - Natural killer (NK) cells and NKT cells play critical early roles in host
      defense. Here we show that MIST, an adaptor protein belonging to the SLP-76
      family, functions negatively in NK cells but positively in CD4(+)NKT cells. NK
      cell receptor-mediated IFN-gamma production was enhanced in NK cells, whereas TCR
      or NK-cell receptor-mediated cytokine production was reduced in CD4(+)NKT cells
      from MIST-deficient mice. These opposite effects of MIST paralleled the exclusive
      expression of the Src family kinase, Fgr, in NK cells between the 2 cell
      populations. We further demonstrated that interaction of MIST with Fgr, mediated
      by the C-terminal proline-rich region of MIST and the SH3 domain of Fgr, was
      required for the suppression of NK-cell receptor-induced IFN-gamma production.
      This functional interdependence of signaling molecules demonstrates a new
      mechanism by which adaptor proteins can act as molecular switches to control
      diverse responses in different cell populations.

PMID- 16439676
TI  - Rapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical
      inhibitor of IKKbeta.
AB  - The transcription factor NF-kappaB plays a central role in regulating
      inflammation and apoptosis, making it a compelling target for drug development.
      We identified a small molecule inhibitor (ML120B) that specifically inhibits
      IKKbeta, an Ikappa-B kinase that regulates NF-kappaB. IKKbeta and NF-kappaB are
      required in vivo for prevention of TNFalpha-mediated apoptosis. ML120B sensitized
      mouse bone marrow progenitors and granulocytes, but not mature B cells to
      TNFalpha killing in vitro, and induced apoptosis in vivo in the bone marrow and
      spleen within 6 hours of a single oral dose. In vivo inhibition of IKKbeta with
      ML120B resulted in depletion of thymocytes and B cells in all stages of
      development in the bone marrow but did not deplete granulocytes. TNF receptor
      deficient mouse thymocytes and B cells were resistant to ML120B-induced depletion
      in vivo. Surprisingly, surviving bone marrow granulocytes expressed TNFR1 and
      TNFR2 after dosing in vivo with ML120B. Our results show that inhibition of
      IKKbeta with a small molecule in vivo leads to rapid TNF-dependent depletion of T
      and B cells. This observation has several implications for potential use of
      IKKbeta inhibitors for the treatment of inflammatory disease and cancer.

PMID- 16439677
TI  - Functional integrity of the p53-mediated apoptotic pathway induced by the
      nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL).
AB  - Deletions and/or mutations of p53 are relatively rare and late events in the
      natural history of B-cell chronic lymphocytic leukemia (B-CLL). However, it is
      unknown whether p53 signaling is functional in B-CLL and if targeted nongenotoxic
      activation of the p53 pathway by using nutlin-3, a small molecule inhibitor of
      the p53/MDM2 interaction, is sufficient to kill B-CLL cells. In vitro treatment
      with nutlin-3 induced a significant cytotoxicity on primary CD19(+) B-CLL cells,
      but not on normal CD19(+) B lymphocytes, peripheral-blood mononuclear cells, or
      bone marrow hematopoietic progenitors. Among 29 B-CLL samples examined, only one
      was resistant to nutlin-3-mediated cytotoxicity. The induction of p53 by nutlin-3
      in B-CLL samples was accompanied by alterations of the mitochondrial potential
      and activation of the caspase-dependent apoptotic pathway. Among several genes
      related to the p53 pathway, nutlin-3 up-regulated the steady-state mRNA levels of
      PCNA, CDKN1A/p21, GDF15, TNFRSF10B/TRAIL-R2, TP53I3/PIG3, and GADD45. This
      profile of gene activation showed a partial overlapping with that induced by the
      genotoxic drug fludarabine. Moreover, nutlin-3 synergized with both fludarabine
      and chlorambucil in inducing B-CLL apoptosis. Our data strongly suggest that
      nutlin-3 should be further investigated for clinical applications in the
      treatment of B-CLL.

PMID- 16439678
TI  - Two new human DMT1 gene mutations in a patient with microcytic anemia, low
      ferritinemia, and liver iron overload.
AB  - DMT1 mediates the pH-dependent uptake of Fe(2+) from the diet in duodenal
      enterocytes and in most other cells. It transfers iron from the endosomes to the
      cytosol following the uptake of the transferrin-transferrin receptor complex.
      DMT1 mutations are responsible for severe hypochromic microcytic anemia in
      rodents and in 2 human patients described recently. We report a compound
      heterozygote for 2 new DMT1 mutations, associated with microcytic anemia from
      birth and progressive liver iron overload. The first mutation is a GTG deletion
      in exon 5, leading to the V114 in-frame deletion in transmembrane domain 2, and
      the second is a G --> T substitution in exon 8 leading to the G212V replacement
      in transmembrane domain 5. Together with the 2 previously reported cases, this
      patient defines a new syndrome of congenital microcytic hypochromic anemia,
      poorly responsive to oral iron treatment, with liver iron overload associated
      paradoxically with normal to moderately elevated serum ferritin levels.

PMID- 16439679
TI  - Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells.
AB  - Activation-induced cytidine deaminase (AID) is necessary for immunoglobulin
      somatic hypermutation (SHM) and class switch recombination (CSR) in T-dependent
      immune response in germinal centers (GCs). The structural similarity of AID with
      RNA-editing enzymes and its largely cytoplasmic location have fueled
      controversial views of its mode of interaction with DNA. We show that AID, a
      mature B-cell-restricted cytoplasmic antigen, is relocated into the nucleus in
      2.5% of CDKN1B(-), CCNB1(-) GC cells. The GC dark zone and the outer zone (OZ),
      but not the light zone, contain nuclear and cytoplasmic AID(+) blasts. AID(+)
      cells in the OZ are in contact with T cells and CD23(-) follicular dendritic
      cells. In addition, AID is expressed in extrafollicular large proliferating B
      cells, 14% of which have nuclear AID. GC and extrafollicular AID(+) cells express
      E47 but not the inhibiting BHLH protein Id2. Outside the GC, AID(+) B cells are
      in contact with T cells and show partial evidence of CD40 plus bcr stimulation
      dependent signature (CCL22, JunB, cMYC, CD30) but lack early and late plasma cell
      markers. The distribution of nuclear AID is consistent with the topography of SHM
      and CSR inside the GC and in extrafollicular activated B cells.

PMID- 16439680
TI  - Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis:
      patients can have both monoclonal gammopathies and hereditary amyloid proteins.
AB  - Investigators in the United Kingdom have shown that hereditary amyloidosis can be
      misdiagnosed as Ig light-chain (AL) amyloidosis because family history is an
      ineffective screen, and tissue staining used to type amyloid is unreliable.
      Misdiagnosis of AL can lead to inappropriate use of chemotherapy and failure to
      diagnose a hereditary disease. Over a 3-year period we sought to determine how
      often both possible sources of amyloidosis occurred in the same patient. We
      employed an algorithm based on established data and patterns of amyloidosis in
      order to focus the screening effort. Of 178 consecutive patients referred for
      amyloidosis, 54 were screened by polymerase chain reaction techniques with
      primers designed to detect transthyretin, apolipoprotein AI, apolipoprotein AII,
      fibrinogen Aalpha, and lysozyme variants. Three patients (6% of those screened
      and 2% of symptomatic patients) had both a monoclonal gammopathy and a hereditary
      variant. These results justify further study of screening for hereditary variants
      in patients with apparent AL, and highlight the need for practical techniques for
      identifying fibrils extracted from tissue.

PMID- 16439681
TI  - Contribution of alpha6 integrins to hematopoietic stem and progenitor cell homing
      to bone marrow and collaboration with alpha4 integrins.
AB  - The laminin receptor integrin alpha6 chain is ubiquitously expressed in human and
      mouse hematopoietic stem and progenitor cells. We have studied its role for
      homing of stem and progenitor cells to mouse hematopoietic tissues in vivo. A
      function-blocking anti-integrin alpha6 antibody significantly reduced progenitor
      cell homing to bone marrow (BM) of lethally irradiated mice, with a corresponding
      retention of progenitors in blood. Remarkably, the anti-integrin alpha6 antibody
      profoundly inhibited BM homing of long-term multilineage engrafting stem cells,
      studied by competitive repopulation assay and analysis of donor-derived
      lymphocytes and myeloid cells in blood 16 weeks after transplantation. A similar
      profound inhibition of long-term stem cell homing was obtained by using a
      function-blocking antibody against alpha4 integrin, studied in parallel.
      Furthermore, the anti-integrin alpha6 and alpha4 antibodies synergistically
      inhibited homing of short-term repopulating stem cells. Intravenous injection of
      anti-integrin alpha6 antibodies, in contrast to antibodies against alpha4
      integrin, did not mobilize progenitors or enhance cytokine-induced mobilization
      by G-CSF. Our results provide the first evidence for a distinct functional role
      of integrin alpha6 receptor during hematopoietic stem and progenitor cell homing
      and collaboration of alpha6 integrin with alpha4 integrin receptors during homing
      of short-term stem cells.

PMID- 16439682
TI  - Epstein-Barr virus nuclear antigen 2 induces FcRH5 expression through CBF1.
AB  - Fc-receptor homolog 5 (FcRH5) is a recently identified B-cell membrane protein of
      unknown function. In Burkitt lymphoma cell lines with chromosome 1q21
      abnormalities, FcRH5 expression is deregulated, implicating FcRH5 in
      lymphomagenesis. Epstein-Barr virus infects and immortalizes B cells, and is
      implicated in the etiology of several tumors of B-cell origin. Overexpression of
      genes located on 1q21-25 has been proposed as a surrogate for Epstein-Barr virus
      in Burkitt lymphoma. We now report that Epstein-Barr virus nuclear antigen 2
      (EBNA2) markedly induces the expression of the FcRH5 gene, encoded on chromosome
      1q21. Induction occurred in the absence of other viral proteins and did not
      require de novo protein synthesis. EBNA2 lacks a DNA-binding domain and can
      target responsive genes through the host DNA binding protein CBF1. We show that
      induction of FcRH5 by EBNA2 is strictly CBF1 dependent, as it was abolished in
      CBF1-deficient cells. Accordingly, EBNA2 targeted CBF1 binding sites present in
      the FcRH5 promoter in vivo, as detected by chromatin immunoprecipitation. These
      results identify FcRH5 as a novel, direct target of EBNA2 that may contribute to
      the development of Epstein-Barr virus-associated tumors.

PMID- 16439683
TI  - Mobilization as a preparative regimen for hematopoietic stem cell
      transplantation.
AB  - Current myeloablative conditioning regimens for hematopoietic stem cell (HSC)
      transplantation are associated with significant morbidity and mortality. Thus,
      alternative strategies to promote engraftment of infused HSCs with increased
      safety warrant investigation. Using parabiotic mice, we determined that, after
      mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow,
      transited blood, and engrafted in open niches in partner marrow. We then
      hypothesized that mobilization before transplantation might vacate niches and
      improve HSC engraftment. When PeP3(b) mice were treated with AMD3100 at 2 hours
      before the transplantation of 4 x 10(7) marrow cells, donor cell engraftment was
      higher (4.6% +/- 1.1%) than in control animals (no AMD3100; 1.0% +/- 0.24%, P <
      .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and
      marrow cells were transplanted 2 hours after each mobilization, donor cell
      engraftment further increased (9.1% +/- 1.7%, P = .001). In contrast, in similar
      experiments with Balb/cByJ mice that mobilize poorly, there was no difference
      between the donor cell engraftment of AMD3100-treated and control recipients.
      These results indicate that the number of available niches regulates the number
      of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative
      approach for HSC transplantation in genetic and other nonmalignant disorders.

PMID- 16439685
TI  - MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell
      chronic lymphocytic leukemia cells.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation
      of long-lived CD5(+) B lymphocytes. Several drugs currently used in the therapy
      of B-CLL act, at least partially, through activation of the p53 pathway.
      Recently, nongenotoxic small-molecule activators of p53, the nutlins, have been
      developed that inhibit p53-MDM2 binding. We have investigated the antitumor
      potential of nutlin-3 in B-CLL and find that it can activate the p53 pathway and
      effectively induce apoptosis in cells with wild-type p53, including cells with
      dysfunctional ataxia telangiectasia mutated, but not mutant p53. Nutlin-3
      stabilized p53 and induced p53 target genes, including MDM2, p21(CIP1), PUMA,
      BAX, PIG3, and WIG1. Nutlin-3 synergized with the genotoxic drugs doxorubicin,
      chlorambucil, and fludarabine, but not with acadesine, which induces p53
      independent apoptosis. Normal human T cells showed lower sensitivity to nutlin-3
      than B-CLL cells and no synergism with the genotoxic drugs. These results suggest
      that MDM2 antagonists alone or in combination with chemotherapeutic drugs may
      offer a new treatment option for B-CLL.

PMID- 16439684
TI  - AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity
      in nonhuman primates.
AB  - AMD3100, a bicyclam antagonist of the chemokine receptor CXCR4, has been shown to
      induce rapid mobilization of CD34(+) hematopoietic cells in mice, dogs, and
      humans, offering an alternative to G-CSF mobilization of peripheral-blood
      hematopoietic stem cells. In this study, AMD3100-mobilized CD34(+) cells were
      phenotypically analyzed, marked with Neo(R)-containing retroviral vectors, and
      subsequently transplanted into myeloablated rhesus macaques. We show engraftment
      of transduced AMD3100-mobilized CD34(+) cells with Neo(R) gene marked myeloid and
      lymphoid cells up to 32 months after transplantation, demonstrating the ability
      of AMD3100 to mobilize true long-term repopulating hematopoietic stem cells. More
      AMD3100-mobilized CD34(+) cells are in the G(1) phase of the cell cycle and more
      cells express CXCR4 and VLA-4 compared with G-CSF-mobilized CD34(+) cells. In
      vivo gene marking levels obtained with AMD3100-mobilized CD34(+) cells were
      better than those obtained using CD34(+) cells mobilized with G-CSF alone.
      Overall, these results indicate that AMD3100 mobilizes a population of
      hematopoietic stem cells with intrinsic characteristics different from those of
      hematopoietic stem cells mobilized with G-CSF, suggesting fundamental differences
      in the mechanism of AMD3100-mediated and G-CSF-mediated hematopoietic stem cell
      mobilization. Thus, AMD3100-mobilized CD34(+) cells represent an alternative
      source of hematopoietic stem cells for clinical stem cell transplantation and
      genetic manipulation with integrating retroviral vectors.

PMID- 16439686
TI  - High-density lipoprotein hydrolysis by endothelial lipase activates PPARalpha: a
      candidate mechanism for high-density lipoprotein-mediated repression of leukocyte
      adhesion.
AB  - Although high-density lipoprotein (HDL) is known to inhibit endothelial adhesion
      molecule expression, the mechanism for this anti-inflammatory effect remains
      obscure. Surprisingly, we observed that HDL no longer decreased adhesion of U937
      monocytoid cells to tumor necrosis factor (TNF)alpha-stimulated human endothelial
      cells (EC) in the presence of the general lipase inhibitor tetrahydrolipstatin.
      In considering endothelial mechanisms responsible for this effect, we found that
      endothelial lipase (EL) overexpression in both EC and non-EL-expressing NIH/3T3
      mouse embryonic fibroblasts cells significantly decreased TNFalpha-induced VCAM1
      expression and promoter activity in a manner dependent on HDL concentration and
      intact EL activity. Given recent evidence for lipolytic activation of peroxisome
      proliferator-activated receptors (PPARs)-nuclear receptors implicated in
      metabolism, atherosclerosis, and inflammation-we hypothesized HDL hydrolysis by
      EL is an endogenous endothelial mechanism for PPAR activation. In both EL
      transfected NIH cells and bovine EC, HDL significantly increased PPAR ligand
      binding domain activation in the order PPAR-alpha> >-gamma>-delta. Moreover, HDL
      stimulation induced expression of the canonical PPARalpha-target gene acyl-CoA
      oxidase (ACO) in a PPARalpha-dependent manner in ECs. Conditioned media from EL
      adenovirus transfected cells but not control media exposed to HDL also activated
      PPARalpha. PPARalpha activation by EL was most potent with HDL as a substrate,
      with lesser effects on LDL and VLDL. Finally, HDL inhibited leukocyte adhesion to
      TNFalpha-stimulated ECs isolated from wild-type but not PPARalpha-deficient mice.
      This data establishes HDL hydrolysis by EL as a novel, distinct natural pathway
      for PPARalpha activation and identifies a potential mechanism for HDL-mediated
      repression of VCAM1 expression, with significant implications for both EL and
      PPARs in inflammation and vascular biology.

PMID- 16439687
TI  - Exercise can prevent and reverse the severity of hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common form of sudden death in
      young competitive athletes. However, exercise has also been shown to be
      beneficial in the setting of other cardiac diseases. We examined the ability of
      voluntary exercise to prevent or reverse the phenotypes of a murine model of HCM
      harboring a mutant myosin heavy chain (MyHC). No differences in voluntary cage
      wheel performance between nontransgenic (NTG) and HCM male mice were seen.
      Exercise prevented fibrosis, myocyte disarray, and induction of "hypertrophic"
      markers including NFAT activity when initiated before established HCM pathology.
      If initiated in older HCM animals with documented disease, exercise reversed
      myocyte disarray (but not fibrosis) and "hypertrophic" marker induction. In
      addition, exercise returned the increased levels of phosphorylated GSK-3beta to
      those of NTG and decreased levels of phosphorylated CREB in HCM mice to normal
      levels. Exercise in HCM mice also favorably impacted components of the apoptotic
      signaling pathway, including Bcl-2 (an inhibitor of apoptosis) and procaspase-9
      (an effector of apoptosis) expression, and caspase-3 activity. Remarkably, there
      were no differences in mortality between exercised NTG and HCM mice. Thus, not
      only was exercise not harmful but also it was able to prevent and even reverse
      established cardiac disease phenotypes in this HCM model.

PMID- 16439688
TI  - CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent
      vasoregenerative capacities.
AB  - Our goal was to identify functionally important subpopulations within the
      heterogenous group of endothelial progenitor cells (EPC). Fluorescence-activated
      cell sorter analysis of CD133+ progenitor cells revealed the presence of CD34+
      and CD34- subpopulations. CD34-/133+ progenitors differentiate into CD34+/133+
      EPC, adhere more potently than these in response to SDF-1, and rapidly home to
      sites of limb ischemia in human volunteers. In human coronary atherectomy
      samples, fewer CD34-/133+ than CD34+/133+ EPC are present in stable plaques,
      whereas cell numbers increase with a reversion of the ratio in unstable lesions.
      In CD34-/133+ EPC-injected nude mice, more transplanted cells coexpressing
      endothelial markers home to carotid artery lesion endothelium than in CD34+/133+
      injected mice. In the former, lesions were smaller and reendothelialization
      higher than in the latter. We identified a new CD34-/133+ EPC subpopulation,
      which is apparently a precursor of "classical" CD34+/133+ EPC, and functionally
      more potent than these with respect to homing and vascular repair.

PMID- 16439689
TI  - Neuronal chemorepellent Slit2 inhibits vascular smooth muscle cell migration by
      suppressing small GTPase Rac1 activation.
AB  - The Slits are secreted proteins with roles in axonal guidance and leukocyte
      migration. On binding to Robo receptors, Slit2 repels developing axons and
      inhibits leukocyte chemotaxis. Slit2 is cleaved into Slit2-N, a protein tightly
      binding to cell membranes, and Slit2-C, a diffusible fragment. In the present
      study, we characterized the functional role of Slit2-N in vascular smooth muscle
      cells (VSMCs) and the cell association properties of 2 truncated versions of
      Slit2-N. Here, we document for the first time that Slit2-N is a chemorepellent of
      VSMCs. Intact blood vessels expressed Slit2 and Robo receptors as demonstrated by
      immunohistochemistry and quantitative real time PCR. Recombinant Slit2-N
      prevented the platelet-derived growth factor (PDGF)-stimulated migration of
      VSMCs. Slit2-N also abrogated PDGF-mediated activation of small guanosine
      triphosphatase (GTPase) Rac1, a member of the Rho GTPase superfamily of proteins
      involved in regulating the actin cytoskeleton. Furthermore, Slit2-N inhibited the
      PDGF-induced formation of lamellipodia, a crucial cytoskeletal reorganization
      event for cell motility. Slit2-N had no effect on the PDGF-mediated increase in
      DNA synthesis determined by [3H]thymidine uptake, suggesting that VSMC growth is
      unaffected by Slit2. Analysis of 2 engineered Slit2-N fragments (Slit2-N/1118 and
      Slit2-N/1121) indicated that 3 amino acids upstream of the putative cleavage site
      (Arg1121, Thr1122) are involved in the association of Slit2-N to the cell
      membrane. Our data assign a novel functional role to Slit2 in vascular function
      and show that cell guidance mechanisms that operate in the developing central
      nervous system are conserved in VSMCs.

PMID- 16439690
TI  - Elevated homocysteine reduces apolipoprotein A-I expression in
      hyperhomocysteinemic mice and in males with coronary artery disease.
AB  - Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by
      nutritional or genetic disturbances in homocysteine metabolism. A polymorphism in
      methylenetetrahydrofolate reductase (MTHFR) is the most common genetic cause of
      mild hyperhomocysteinemia. To examine mechanisms by which an elevation in plasma
      homocysteine leads to vascular disease, we first performed microarray analyses in
      livers of Mthfr-deficient mice and identified differentially expressed genes that
      are involved in lipid and cholesterol metabolism. Microarrays and RT-PCR showed
      decreased mRNA for apolipoprotein A (ApoA)-IV and for ApoA-I and increased mRNA
      for cholesterol 7alpha hydroxylase (Cyp7A1) in Mthfr(+/-) mice compared with
      Mthfr(+/+) mice. Western blotting revealed that ApoA-I protein levels in liver
      and plasma of Mthfr(+/-) mice were 52% and 62% of levels in the respective
      tissues of Mthfr(+/+) mice. We also performed Western analysis for plasma ApoA-I
      protein levels in 60 males with coronary artery disease and identified a
      significant (P<0.01) negative correlation (-0.33) between ApoA-I and plasma
      homocysteine levels. This cohort also displayed a negative correlation (-0.24,
      P=0.06) between high-density lipoprotein cholesterol and plasma homocysteine.
      Treatment of HepG2 cells with supraphysiological levels of 5 mmol/L homocysteine
      reduced peroxisome proliferator-activated receptor (PPAR) alpha and ApoA-I
      protein levels and decreased ApoA-I promoter activity. Transfection with a
      PPARalpha construct upregulated ApoA-I and MTHFR. Our results suggest that
      hyperhomocysteinemia may increase risk of atherosclerosis by decreasing
      expression of ApoA-I and increasing expression of CYP7A1.

PMID- 16439691
TI  - NBCn1 (slc4a7) mediates the Na+-dependent bicarbonate transport important for
      regulation of intracellular pH in mouse vascular smooth muscle cells.
AB  - The contribution of sodium-dependent bicarbonate transport to intracellular pH
      (pH(i)) regulation in vascular smooth muscle cells is controversial, partly
      because the molecular identity of the transporter(s) responsible has not been
      identified. Here, using the pH-sensitive fluorophore 2',7'-bis-(2-carboxyethyl)-5
      (and-6)-carboxyfluorescein (BCECF), we show that smooth muscle cells of intact
      mouse mesenteric, coronary, and cerebral small arteries all display a sodium- and
      bicarbonate-dependent pH(i) recovery after an NH4+-prepulse. The sodium-dependent
      bicarbonate flux was largely 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid
      (DIDS) sensitive (56% to 91%) and of a magnitude similar to the amiloride
      sensitive flux. Additionally, steady-state pH(i) was lower (0.2 to 0.4 pH units
      magnitude) in all 3 vascular beds when CO2/bicarbonate was omitted. RT-PCR
      analyses showed that NBCn1 (slc4a7) is the only Na+-dependent bicarbonate
      transporter of the slc4 family detectable at the mRNA level in all 3 vascular
      beds investigated. Whole-mount immunolabeling and immunogold electron microscopy
      confirmed the presence of NBCn1 protein in the sarcolemma of mouse mesenteric
      small arterial smooth muscle cells. Intact mouse mesenteric small arteries were
      electropermeated to facilitate transfection with small interfering RNA targeting
      NBCn1, which resulted in an approximate 43% decrease in the ratio of NBCn1 to
      glyceraldehyde-3-phosphate dehydrogenase mRNA. After knock-down, we found a
      decreased steady-state pH(i) (0.21+/-0.08 pH units) as well as a 68+/-10%
      decrease in the net Na+-dependent, amiloride-insensitive base influx after acid
      load. Finally, omission of CO2/bicarbonate resulted in a decreased contractile
      response to norepinephrine after sustained exposure to the agonist, underlining
      the importance of CO2/bicarbonate for vascular contractility. We conclude that
      NBCn1 mediates the Na+-dependent bicarbonate transport important for pH(i)
      regulation in smooth muscle cells of mouse mesenteric, coronary, and cerebral
      small arteries.

PMID- 16439692
TI  - Interferon-gamma induces major histocompatibility class II transactivator
      (CIITA), which mediates collagen repression and major histocompatibility class II
      activation by human aortic smooth muscle cells.
AB  - Chronic inflammation in atherosclerosis is responsible for plaque instability
      through alterations in extracellular matrix. Previously, we demonstrated that
      major histocompatibility class II (MHC II) transactivator (CIITA) in a complex
      with regulatory factor for X box 5 (RFX5) is a crucial protein mediating
      interferon (IFN)-gamma-induced repression of collagen type I gene transcription
      in fibroblasts. This article demonstrates that, in smooth muscle cells (SMCs),
      IFN-gamma dramatically increases the expression of CIITA isoforms III and IV,
      with no increase in expression of CIITA isoform I. Expression of CIITA III and IV
      correlates with decreased collagen type I and increased MHC II gene expression.
      Exogenous expression of CIITA I, III, and IV, in transiently transfected SMCs,
      represses collagen type I promoters (COL1A1 and COL1A2) and activates MHC II
      promoter. Levels of CIITA and RFX5 increase in the nucleus of cells treated with
      IFN-gamma. Moreover, simvastatin lowers the IFN-gamma-induced expression of RFX5
      and MHC II in addition to repressing collagen expression. However, simvastatin
      does not block the IFN-gamma-induced expression of CIITA III and IV, suggesting a
      CIITA-independent mechanism. This first demonstration that RFX5 and CIITA
      isoforms are expressed in SMCs after IFN-gamma stimulation suggest that CIITA
      could be a key factor in plaque stability in atherosclerosis.

PMID- 16439694
TI  - Hemorrhage in the Interventional Management of Stroke study.
AB  - BACKGROUND AND PURPOSE: The incidence of hemorrhage after combined intravenous
      (IV) and intra-arterial (IA) recombinant tissue plasminogen activator (rt-PA) was
      examined in patients entered into the Interventional Management of Stroke (IMS)
      trial. We also analyzed factors predicting symptomatic and asymptomatic
      intracerebral hemorrhage (ICH). METHODS: The IMS study treated patients within 3
      hours of stroke onset with 0.6 mg/kg IV rt-PA followed by up to 22 mg IA rt-PA.
      Any hemorrhage within 36 hours associated with clinical deterioration was
      considered symptomatic. Logistic regression analysis was applied to possibly
      relevant variables selected from the baseline data to test for associations
      between these factors and symptomatic hemorrhage, asymptomatic hemorrhage, and
      all hemorrhage. RESULTS: Symptomatic hemorrhage occurred in 6% and asymptomatic
      hemorrhage in 43% of patients. The rate of symptomatic hemorrhage was similar to
      the National Institute of Neurological Disorders and Stroke (NINDS) trial with IV
      rt-PA alone. Asymptomatic hemorrhage was more frequent but consistent with the
      rate observed in more recent IV and IA thrombolytic trials. The small number of
      symptomatic hemorrhages precluded meaningful analysis of risk factors.
      Significant factors associated with ICH in univariate analysis were baseline
      National Institutes of Health Stroke Scale score (asymptomatic and all ICH),
      edema or mass effect on initial computed tomography (asymptomatic ICH), atrial
      fibrillation (all ICH), and location of arterial occlusion (internal carotid
      artery [ICA] compared with middle cerebral artery [MCA]; asymptomatic and all
      ICH). In multivariate analysis, ICA versus MCA occlusion remained an independent
      factor associated with asymptomatic and all hemorrhage, and atrial fibrillation
      was significantly associated with all hemorrhage. CONCLUSIONS: Symptomatic and
      asymptomatic hemorrhage with combined IV and IA rt-PA occurred at rates similar
      to previous thrombolytic trials. Site of vascular occlusion and atrial
      fibrillation may be risk factors for hemorrhagic transformation.

PMID- 16439693
TI  - Upregulated TRPC1 channel in vascular injury in vivo and its role in human
      neointimal hyperplasia.
AB  - Occlusive vascular disease is a widespread abnormality leading to lethal or
      debilitating outcomes such as myocardial infarction and stroke. It is part of
      atherosclerosis and is evoked by clinical procedures including angioplasty and
      grafting of saphenous vein in bypass surgery. A causative factor is the switch in
      smooth muscle cells to an invasive and proliferative mode, leading to neointimal
      hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of
      Drosophila transient receptor potential. Using 2 different in vivo models of
      vascular injury in rodents we show hyperplasic smooth muscle cells have
      upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity.
      Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery
      also express TRPC1. Furthermore, human vein samples obtained during coronary
      artery bypass graft surgery commonly exhibit an intimal structure containing
      smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins
      were organ cultured to allow growth of neointimal smooth muscle cells over a 2
      week period. To explore the functional relevance of TRPC1, we used a specific E3
      targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate.
      Both agents significantly reduced neointimal growth in human vein, as well as
      calcium entry and proliferation of smooth muscle cells in culture. The data
      suggest upregulated TRPC1 is a general feature of smooth muscle cells in
      occlusive vascular disease and that TRPC1 inhibitors have potential as protective
      agents against human vascular failure.

PMID- 16439695
TI  - Hydrogen sulfide is a mediator of cerebral ischemic damage.
AB  - BACKGROUND AND PURPOSE: We observed recently that elevated plasma cysteine levels
      are associated with poor clinical outcome in acute stroke patients. In a rat
      stroke model, cysteine administration increased the infarct volume apparently via
      its conversion to hydrogen sulfide (H2S). We therefore investigated the effects
      of H2S and the inhibition of its formation on stroke. METHODS: Cerebral ischemia
      was studied in a rat stroke model created by permanent occlusion of the middle
      cerebral artery (MCAO). The resultant infarct volume was measured 24 hours after
      occlusion. RESULTS: Administration of sodium hydrosulfide (NaHS, an H2S donor)
      significantly increased the infarct volume after MCAO. The NaHS-induced increase
      in infarct volume was abolished by the administration of dizolcilpine maleate (an
      N-methyl-d-aspartate receptor channel blocker). MCAO caused an increase in H2S
      level in the lesioned cortex as well as an increase in the H2S synthesizing
      activity. Administration of 4 different inhibitors of H2S synthesis reduced MCAO
      induced infarct volume dose dependently. The potency of these inhibitors in
      effecting neuroprotection in vivo appeared to parallel their potency as
      inhibitors of H2S synthesis in vitro. It also appeared that most of the H2S
      synthesizing activity in the cortex results from the action of cystathionine beta
      synthase. CONCLUSIONS: The present results strongly suggest that H2S plays a part
      in cerebral ischemic damage after stroke. Inhibition of H2S synthesis should be
      investigated for its potential as a novel neuroprotective stroke therapy.

PMID- 16439697
TI  - Ten-year incidence of retinal emboli in an older population.
AB  - BACKGROUND AND PURPOSE: To assess 10-year incidence of retinal emboli and its
      predictors in an older population. METHODS: Survivors of 3654 Blue Mountains Eye
      Study participants > or =49 years of age were re-examined 5 and 10 years later.
      Incident emboli were assessed from retinal photographs. RESULTS: Cumulative 10
      year incidence was 2.9% (95% CI, 2.1% to 3.6%) among 2361 at risk. Age was
      associated with incident emboli (Ptrend=0.0001). After multivariate adjustment,
      hypertension (odds ratio [OR], 1.8; CI, 1.0 to 3.1), hypercholesterolemia (OR,
      1.3; CI, 1.0 to 1.6), overweight (OR, 3.3; CI, 1.6 to 6.9), current smoking (OR,
      2.5; CI, 1.1 to 5.9), increasing fibrinogen level (OR per mg/dL, 1.1; CI, 1.0 to
      1.2), and retinal vascular signs (arteriovenous nicking OR, 2.0; CI, 1.2 to 3.6;
      arteriolar wall opacification OR, 2.3; CI, 1.1 to 5.0; retinal vein occlusion OR,
      3.2; CI, 1.0 to 9.9) were significantly associated with incident emboli.
      CONCLUSIONS: The 3% incidence of retinal arteriolar emboli found in this older
      population is likely to be an underestimate attributable to the transient nature
      of emboli and differential loss to follow-up. Most cardiovascular risk factors
      predict retinal embolism.

PMID- 16439696
TI  - Outcome and symptomatic bleeding complications of intravenous thrombolysis within
      6 hours in MRI-selected stroke patients: comparison of a German multicenter study
      with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials.
AB  - BACKGROUND AND PURPOSE: We compared outcome and symptomatic bleeding
      complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours
      of symptom onset in MRI-selected patients with acute middle cerebral artery
      infarction with the pooled data of the large stroke tPA trials. METHODS: Patients
      were examined by perfusion-weighted and diffusion-weighted imaging < or =6 hours.
      Within 3 hours, patients were treated according to Second European-Australasian
      Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA
      was performed based on MRI findings. Favorable outcome was assessed after 90 days
      using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral
      bleeding complications were assessed on follow-up MRI or computed tomography.
      Data were compared with the pooled placebo and pooled tPA patients of the
      ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke
      (NINDS) tPA trials. RESULTS: From 174 MRI-selected tPA patients, 62% (n=108) were
      treated in < or =3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was
      more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with
      pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40%
      [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI
      selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and
      1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic
      intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was
      lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable
      to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392). CONCLUSIONS: This
      study supports that it is safe and effective to expand the time window for IV-tPA
      up to 6 hours in patients with tissue at risk as defined by MRI.

PMID- 16439699
TI  - Subclinical carotid atherosclerosis in HIV-infected patients: role of combination
      antiretroviral therapy.
AB  - BACKGROUND AND PURPOSE: Whether or not combination antiretroviral therapy (CART)
      alone directly contributes to accelerating atherosclerosis in HIV-infected
      patients has not been studied in depth. This study aimed to ascertain the
      relationship between this therapy and subclinical carotid atherosclerosis
      according to cardiovascular risk. METHODS: Sixty-eight HIV-infected patients with
      < or =1 cardiovascular risk factors and 64 with > or =2 risk factors completed
      the study protocol consisting of clinical, laboratory, and vascular evaluation by
      carotid high-resolution B-mode ultrasonography. Univariate and multivariate
      logistic regression analyses were performed with the presence of subclinical
      carotid atherosclerosis, defined by carotid intima-media thickness >0.8 mm or the
      presence of plaque being the dependent variable. RESULTS: Among the 132 enrolled
      patients, 93 (70.5%) were on CART and 39 (29.5%) had never been on antiretroviral
      therapy. In accordance with cardiovascular risk stratification, subclinical
      carotid atherosclerosis was found in 26.6% (17 of 64 patients) of the very low
      risk group (10-year coronary risk <5%), 35.3% (12 of 34 patients) of the low-risk
      group (10-year coronary risk between 5% and 9%) and 76.5% (26 of 34 patients) of
      the moderate/high-risk group (10-year coronary risk > or =10%). Thus, 55 (41.7%)
      of the 132 HIV-infected patients had subclinical carotid atherosclerosis, and
      independent variables associated with carotid atherosclerosis (odds ratio; 95%
      CI) were: CART exposure (10.5; 2.8 to 39) and 10-year coronary risk > or =10%
      (4.2; 1.5 to 12). In very low coronary risk patients (<5%), age (per 10-year
      increment: 4.01; 1.12 to 14.38), systolic blood pressure (per unit mm Hg 1.07;
      1.01 to 1.14), and CART exposure (8.65; 1.54 to 48.54) were independently
      associated with subclinical carotid atherosclerosis. CONCLUSIONS: CART should be
      considered a strong, independent predictor for the development of subclinical
      atherosclerosis in HIV-infected patients, regardless of known major
      cardiovascular risk factors and atherogenic metabolic abnormalities induced by
      this therapy.

PMID- 16439700
TI  - Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage caused by cerebral aneurysm
      rupture remains a life-threatening emergency despite advances in treatment.
      However, the mechanisms underlying aneurysm initiation, progression, and rupture
      remain unclear. We developed a method to induce experimental cerebral aneurysms
      in rats, monkeys, and mice. Interleukin-1beta (IL-1beta) is a key inflammatory
      mediator, and it is thought to be a promising target for the treatment of
      inflammatory diseases. In the present study, we examined the role of IL-1beta in
      cerebral aneurysm development. METHODS: Cerebral aneurysms were experimentally
      induced in 5-week-old male C57BL/6 mice, IL-1beta gene-deficient (IL-1beta-/-)
      mice, and age-matched control B10 mice (wild-type). Their cerebral arteries were
      dissected and examined histologically and immunohistochemically. RESULTS: IL
      1beta was expressed in vascular media in mice at an early stage of aneurysmal
      models' cerebral arteries. No differences were seen in the rate of aneurysm
      development between IL-1beta-/- and wild-type mice, but the percentage of
      advanced aneurysm change was significantly larger in wild-type animals.
      Furthermore, in IL-1beta-/- mice, increased caspase-1 expression was seen
      compared with wild-type animals. Additionally, the number of apoptotic cells
      assessed by single-stranded DNA immunoreactivity and TUNEL was significantly
      reduced in IL-1beta-/- mice compared with wild-type animals. CONCLUSIONS: IL
      1beta is important for the progression of cerebral aneurysms in a mouse model.
      Disruption of the IL-1beta gene results in the reduced incidence of mature
      experimental cerebral aneurysms.

PMID- 16439701
TI  - Using change in the National Institutes of Health Stroke Scale to measure
      treatment effect in acute stroke trials.
AB  - BACKGROUND AND PURPOSE: Outcome measures in acute stroke trials are being
      refined. Changes in neurological deficits might be useful outcome measures
      because they can measure the entire spectrum of deficits. METHODS: We analyzed
      data from the acute stroke treatment trial Trial of Org 10172 in Acute Stroke
      Treatment (TOAST). Using logistic regression analysis, we modeled the probability
      of the TOAST predefined very favorable outcome (VFO; both Glasgow Outcome Scale 1
      and modified Barthel Index 19 to 20) at 3 months. Within-subject changes
      (baseline-3 months) on the National Institutes of Health Stroke Scale (NIHSS) was
      the main predictor of interest. RESULTS: The baseline median NIHSS for the entire
      TOAST cohort was 7, and it improved by 4 points (interquartile range 3 to 6)
      among 603 patient with VFO and by 2 points (interquartile range -1 to 5) among
      638 patients without a VFO (P<0.001). The odds for VFO increased by 2.29 (95% CI,
      2.06 to 2.54; P<0.001) for each 1-point improvement on the NIHSS. In receiver
      operating characteristic analysis, final NIHSS < or =2 was a good predictor of
      VFO, but no single NIHSS change cut point was a good predictor of VFO.
      CONCLUSIONS: NIHSS change appears to be a useful outcome measure for acute stroke
      trials and is not fully comparable to dichotomized functional outcomes.

PMID- 16439702
TI  - Therapeutic strategies after examination by transesophageal echocardiography in
      503 patients with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) is the gold
      standard in detecting high-risk (ie, aortic thrombi) and potential sources (ie,
      patent foramen ovale [PFO]) of cerebral embolism. We sought to evaluate the
      additional information and therapeutic impact provided by TEE in stroke patients
      and to characterize patients in whom TEE is indispensable. METHODS: We included
      503 consecutive patients (mean age 62.2 years) with acute brain ischemia. Each
      patient received TEE and the following routine diagnostics: ultrasound of brain
      supplying arteries, ECG or Holter-ECG, transthoracic echocardiography, and brain
      imaging (computed tomography or MRI). Stroke etiology was classified according to
      the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. High-risk
      sources in TEE were: aortic thrombi or plaques > or =4 mm, thrombi in left atrial
      cavity/left atrial appendage, spontaneous echo contrast, and left atrial flow
      velocity <30 cm/s. Potential sources in TEE were PFO, atrial septal aneurysm, and
      aortic plaques <4 mm. RESULTS: Stroke etiology was determined by routine
      diagnostics in 276 of 503 patients (54.9%). Of the remaining 227 patients
      (undetermined etiology), 212 (93.4%) were candidates for oral anticoagulation
      (OA). TEE revealed a high-risk source, with indication for OA in 17 of them
      (8.0%). A potential source leading to OA was found in an additional 48 patients
      (22.6%). The remaining 147 patients (69.3%) were treated by platelet inhibitors
      or statins. CONCLUSIONS: TEE strongly influenced secondary prevention and led to
      OA in one third of our patients with stroke of undetermined etiology. TEE is
      indispensable in all patients being candidates for OA when routine diagnostics
      cannot clarify stroke etiology.

PMID- 16439703
TI  - Prediction of cardiovascular morbidity and mortality: comparison of the internal
      carotid artery resistive index with the common carotid artery intima-media
      thickness.
AB  - BACKGROUND AND PURPOSE: The intima-media thickness (IMT) of the common carotid
      artery (CCA) is well correlated with the degree of arteriosclerosis and is a
      predictor of cardiovascular morbidity and mortality. The (hemodynamic) resistive
      index (RI) of the internal carotid artery (ICA) correlates with the degree of
      arteriosclerosis just as well as IMT. The aim of the study was to compare the
      predictive values of RI and IMT with regard to cardiovascular morbidity and
      mortality. METHODS: A total of 146 patients with cardiovascular risk factors or
      established arteriosclerosis were included. Duplex sonography of the CCA and ICA
      was performed, and the IMT and RI were measured in both vessels. During follow-up
      for a median of 36 months, the occurrence of cardiovascular events (myocardial
      infarction, stroke, or cardiovascular death) was assessed. RESULTS: Thirty-nine
      cardiovascular events occurred in 28 patients (19.2%). The relative risk for a
      cardiovascular event per increase of the IMT by 1 SD (0.16 mm) was 1.53 (95% CI,
      1.07 to 2.18) and 1.91 (95% CI, 1.34 to 2.73) for RI ICA (0.08). The event rate
      in patients with IMT <0.79 mm (mean) and RI ICA <0.66 (mean) was 11.8% and 12.7%
      compared with 25.6% (P=0.03) and 25.0% (P=0.06) in patients with IMT > or =0.79
      mm and RI ICA > or =0.66, respectively. Log rank analysis showed a continuous
      increase in the risk of cardiovascular event with increasing range of the IMT
      (P=0.029) and RI ICA (P<0.001). CONCLUSIONS: The RI ICA is a predictor of
      cardiovascular mortality and morbidity, at least comparable to the well
      established IMT.

PMID- 16439704
TI  - Impact of white matter hyperintensities scoring method on correlations with
      clinical data: the LADIS study.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are associated with
      decline in cognition, gait, mood, and urinary continence. Associations may depend
      on the method used for measuring WMH. We investigated the ability of different
      WMH scoring methods to detect differences in WMH load between groups with and
      without symptoms. METHODS: We used data of 618 independently living elderly with
      WMH collected in the Leukoaraiosis And DISability (LADIS) study. Subjects with
      and without symptoms of depression, gait disturbances, urinary incontinence, and
      memory decline were compared with respect to WMH load measured qualitatively
      using 3 widely used visual rating scales (Fazekas, Scheltens, and Age-Related
      White Matter Changes scales) and quantitatively with a semiautomated volumetric
      technique and an automatic lesion count. Statistical significance between groups
      was assessed with the chi2 and Mann-Whitney tests. In addition, the punctate and
      confluent lesion type with comparable WMH volume were compared with respect to
      the clinical data using Student t test and chi2 test. Direct comparison of visual
      ratings with volumetry was done using curve fitting. RESULTS: Visual and
      volumetric assessment detected differences in WMH between groups with respect to
      gait disturbances and age. WMH volume measurement was more sensitive than visual
      scores with respect to memory symptoms. Number of lesions nor lesion type
      correlated with any of the clinical data. For all rating scales, a clear but
      nonlinear relationship was established with WMH volume. CONCLUSIONS: Visual
      rating scales display ceiling effects and poor discrimination of absolute lesion
      volumes. Consequently, they may be less sensitive in differentiating clinical
      groups.

PMID- 16439705
TI  - Therapy of basilar artery occlusion: a systematic analysis comparing intra
      arterial and intravenous thrombolysis.
AB  - BACKGROUND AND PURPOSE: Basilar artery occlusion (BAO) is an infrequent form of
      acute stroke, which invariably leads to death or long-term disability if not
      recanalized. A traditional recanalization approach based on historical controls
      and pathophysiological consideration is local intra-arterial thrombolysis (IAT)
      in eligible patients. This necessitates diagnostic evaluation and treatment in
      stroke centers equipped with an interventional neuroradiological service on a 24
      hour basis, but its superiority to the technically simple intravenous
      thrombolysis (IVT) remains unproven. METHODS: We analyzed systematically
      published case series of substantial size reporting the outcome of BAO after IAT
      or IVT. RESULTS: In 420 BAO patients treated with IVT (76) and IAT (344), death
      or dependency were equally common: 78% (59 of 76) and 76% (260 of 344),
      respectively (P=0.82). Recanalization was achieved more frequently with IAT (225
      of 344; 65%) than with IVT (40 of 76; 53%; P=0.05), but survival rates after IVT
      (38 of 76; 50%) and IAT (154 of 344; 45%) were equal (P=0.48). A total of 24% of
      patients treated with IAT and 22% treated with IVT reached good outcomes
      (P=0.82). Without recanalization, the likelihood of good outcome was close to nil
      (2%). CONCLUSIONS: Recanalization occurs in more than half of BAO patients
      treated with IAT or IVT, and 45% to 55% of survivors regain functional
      independence. Although improved therapy forms for BAO are necessary, hospitals
      not equipped for IAT may set up IVT protocols. The effect of IVT is probably not
      much different from the effect of IAT. IVT represents probably the best treatment
      that can be offered to victims of acute BAO in such hospitals.

PMID- 16439706
TI  - Glucose-6-phosphate dehydrogenase deficiency decreases vascular superoxide and
      atherosclerotic lesions in apolipoprotein E(-/-) mice.
AB  - OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the
      pentose phosphate pathway that is a major source of cellular NADPH. The purpose
      of this study was to examine whether G6PD deficiency affects vascular oxidants
      and atherosclerosis in high-fat fed apolipoprotein (apo) E(-/-) mice. METHODS AND
      RESULTS: G6PD-mutant mice whose G6PD activity was 20% of normal were crossbred
      with apoE(-/-) mice. Among male apoE(-/-) mice that were fed a western-type diet
      for 11 weeks, G6PD wild-type (E-WT), and G6PD hemizygous (E-Hemi) mice were
      compared. Basal blood pressure was significantly higher in E-Hemi. However,
      superoxide anion release, nitrotyrosine, vascular cell adhesion molecule (VCAM)
      1, and inducible nitric oxide synthase immunohistochemical staining were less in
      E-Hemi compared with E-WT aorta. Serum cholesterol level was lower in E-Hemi, but
      aortic lesion area was decreased in E-Hemi even after adjusting for serum
      cholesterol. CONCLUSIONS: Lower NADPH production in G6PD deficiency may result in
      lower NADPH oxidase-derived superoxide anion, and thus lower aortic lesion
      growth. The association of higher blood pressure with lower serum cholesterol
      levels in this mouse model is indicative of the complex effects that G6PD
      deficiency may have on vascular disease.

PMID- 16439707
TI  - Angiotensin II attenuates endothelium-dependent responses in the cerebral
      microcirculation through nox-2-derived radicals.
AB  - OBJECTIVE: Angiotensin II (Ang II) exerts deleterious effect on the cerebral
      circulation through production of reactive oxygen species (ROS). However, the
      enzymatic source of the ROS has not been defined. We tested the hypothesis that
      Ang II impairs endothelium-dependent responses in the cerebral microcirculation
      through ROS generated in cerebrovascular cells by the enzyme NADPH oxidase.
      METHODS AND RESULTS: Cerebral blood flow (CBF) was monitored by laser Doppler
      flowmetry in anesthetized mice equipped with a cranial window. Ang II (0.25+/
      0.02 microg/kg per minute for 30 to 45 minutes) attenuated the CBF increase
      produced by the endothelium-dependent vasodilators acetylcholine (-42+/-5%;
      P<0.05), bradykinin (-53+/-5%; P<0.05), and A23187 (-43+/-4%; P<0.05), and
      induced cerebrovascular ROS production, assessed by hydroethidine
      fluoromicrography. These actions of Ang II were prevented by losartan, by the ROS
      scavenger Mn(III) tetrakis (4-benzoic acid) porphyrin chloride (100 micromol/L),
      or by the NADPH oxidase peptide inhibitor gp91ds-tat (1 micromol/L), and were not
      observed in mice lacking the NADPH oxidase subunit gp91phox (nox-2). CONCLUSIONS:
      Ang II impairs the endothelial regulation of the cerebral microcirculation
      through AT1 receptor-mediated cerebrovascular oxidative stress. The source of the
      ROS is a nox-2-containing NADPH oxidase. These effects of Ang II could threaten
      the cerebral blood supply and contribute to the increased susceptibility to
      stroke and dementia associated with hypertension.

PMID- 16439708
TI  - Non-exercise activity thermogenesis: the crouching tiger hidden dragon of
      societal weight gain.
AB  - Non-exercise activity thermogenesis (NEAT) is the energy expenditure of all
      physical activities other than volitional sporting-like exercise. NEAT includes
      all the activities that render us vibrant, unique, and independent beings such as
      working, playing, and dancing. Because people of the same weight have markedly
      variable activity levels, it is not surprising that NEAT varies substantially
      between people by up to 2000 kcal per day. Evidence suggests that low NEAT may
      occur in obesity but in a very specific fashion. Obese individuals appear to
      exhibit an innate tendency to be seated for 2.5 hours per day more than sedentary
      lean counterparts. If obese individuals were to adopt the lean "NEAT-o-type,"
      they could potentially expend an additional 350 kcal per day. Obesity was rare a
      century ago and the human genotype has not changed over that time. Thus, the
      obesity epidemic may reflect the emergence of a chair-enticing environment to
      which those with an innate tendency to sit, did so, and became obese. To reverse
      obesity, we need to develop individual strategies to promote standing and
      ambulating time by 2.5 hours per day and also re-engineer our work, school, and
      home environments to render active living the option of choice.

PMID- 16439709
TI  - Increased serum cadmium and strontium levels in young smokers: effects on
      arterial endothelial cell gene transcription.
AB  - OBJECTIVE: Metal constituents of tobacco have long been suspected to contribute
      to cardiovascular diseases. In this study, we determined the serum concentrations
      of aluminum, cadmium (Cd), cobalt, copper, iron, manganese, nickel, lead,
      strontium (Sr), and zinc of young nonsmokers, passive smokers, and smokers.
      METHODS AND RESULTS: Cd and Sr were found to be significantly increased in
      smokers compared with nonsmokers. The effects of these metals on primary arterial
      endothelial cells were then assessed using microarray technology and real-time
      polymerase chain reaction (RT-PCR). The data showed that Sr does not interfere
      with endothelial cell transcription. In contrast, the effects of Cd in amounts
      delivered to the human body by smoking were dramatic. CONCLUSIONS: Arterial
      endothelial cells responded to Cd exposure by massively upregulating metal and
      oxidant defense genes (metallothioneins) and by downregulating a number of
      transcription factors. In addition, the mRNA of the intermediate filament protein
      vimentin, crucial for the maintenance of cellular shape, was reduced.
      Surprisingly, a number of pro-inflammatory genes were downregulated in response
      to Cd. The present data suggest that by delivering Cd to the human body, smoking
      deregulates transcription, exerts stress, and damages the structure of the
      vascular endothelium; furthermore, in contrast to the effects of cigarette smoke
      as a whole, Cd seems to possess anti-inflammatory properties.

PMID- 16439710
TI  - Granulocyte colony-stimulating factor-mobilized circulating c-Kit+/Flk-1+
      progenitor cells regenerate endothelium and inhibit neointimal hyperplasia after
      vascular injury.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) treatment was shown to
      inhibit neointimal formation of balloon-injured vessels, whereas neither the
      identification of progenitor cells involved in G-CSF-mediated endothelial
      regeneration with a bone marrow (BM) transplant experiment nor the functional
      properties of regenerated endothelium have been studied. METHODS AND RESULTS:
      Recombinant human G-CSF (100 microg/kg per day) was injected daily for 14 days
      starting 3 days before balloon injury in the rat carotid artery. Neointimal
      formation of denuded vessels on day 14 was markedly attenuated by G-CSF (39%
      versus the control; P<0.05). Endothelial cell-specific immunostaining revealed an
      enhancement of re-endothelialization (1.8-fold increase versus the control;
      P<0.05) and inhibition of extravasation of Evans Blue dye (47%; P=0.02). The
      regenerated endothelium exhibited acetylcholine-mediated vasodilatation in NO
      dependent manner. G-CSF increased the circulating c-Kit+/Flk-1+ cells (9.1-fold;
      P<0.02), which showed endothelial properties in vitro (acetylated low-density
      lipoprotein uptake and lectin binding) and incorporated into the regenerated
      endothelium in vivo. A BM replacement experiment with green fluorescent protein
      (GFP)-overexpressing cells showed that BM-derived GFP+/CD31+ endothelial cells
      occupied 39% of the total luminal length in the G-CSF-mediated neo-endothelium
      (2% in the control). CONCLUSIONS: The G-CSF-induced mobilization of BM-derived c
      Kit+/Flk-1+ cells contributes to endothelial regeneration, and this cytokine
      therapy may be a feasible strategy for the promotion of re-endothelialization
      after angioplasty.

PMID- 16439711
TI  - Cholesteryl ester transfer protein (CETP) inhibition beyond raising high-density
      lipoprotein cholesterol levels: pathways by which modulation of CETP activity may
      alter atherogenesis.
AB  - Raising high-density lipoprotein cholesterol (HDL-C) is a promising strategy in
      the struggle to prevent cardiovascular disease, and cholesteryl ester transfer
      protein (CETP) inhibitors have been developed to accomplish this. The first
      results are encouraging, and, in fact, in rabbits, inhibition of CETP reduces
      atherosclerosis. Because human data regarding the reduction of atheroma burden
      require more time, the biochemical mechanisms underlying the putative
      atheroprotection of CETP inhibitors are currently dissected, and several pathways
      have emerged. First, CETP inhibition increases HDL-C and reduces low-density
      lipoprotein cholesterol (LDL-C) levels consistent with CETP lipid transfer
      activity and its role in reverse cholesterol transport (RCT). This coincides with
      putative beneficial increases in both HDL and LDL size. However, many aspects
      regarding the impact of CETP inhibition on the RCT pathway remain elusive, in
      particular whether the first step concerning cholesterol efflux from peripheral
      tissues to HDL is influenced. Moreover, the relevance of scavenger receptor BI
      and consequently the central role of HDL in human RCT is still unclear. Second,
      CETP inhibition was shown recently to increase antioxidant enzymes associated
      with HDL, in turn associated with decreased oxidation of LDL. Atheroprotection in
      man is currently anticipated based on the improvement of these biochemical
      parameters known to influence atherosclerosis, but final confirmation regarding
      the impact of CETP inhibition on cardiovascular outcome will have to come from
      trials evaluating clinical end points.

PMID- 16439712
TI  - Proangiogenic effects of protease-activated receptor 2 are tumor necrosis factor
      alpha and consecutively Tie2 dependent.
AB  - OBJECTIVE: Angiogenesis is essential physiologically in growth and pathologically
      in tumor development, chronic inflammatory disorders, and proliferative
      retinopathies. Activation of protease-activated receptor 2 (PAR2) leads to a
      proangiogenic response, but its mechanisms have yet to be specifically described.
      Here, we investigated the mode of action of PAR2 in retinal angiogenesis. METHODS
      AND RESULTS: PAR2-activating peptide, SLIGRL, increased retinal angiogenesis
      associated with an induction of vascular endothelial growth factor and
      angiopoetin-2 and most notably tie2 in the retina in vivo as well as in cultured
      neuroretinal endothelial cells. SLIGRL also induced release of the
      proinflammatory and angiogenic mediator tumor necrosis factor-alpha (TNF-alpha)
      via the MEK/extracellular signal-regulated kinase (ERK) (MEK/ERK) pathway in
      these endothelial cells. TNF-alpha, in turn, elicited tie2 expression by
      activating the MEK/ERK pathway. PAR2-evoked tie2 expression, endothelium
      proliferation (in vitro), and retinal neovascularization (in vivo) were abrogated
      by selective TNF-alpha blockers (neutralizing antibody infliximab and soluble TNF
      alpha receptor-Fc fusion protein etanercept) as well as the MEK inhibitor
      PD98059. CONCLUSIONS: The proangiogenic properties of PAR2 are intertwined with
      its proinflammatory effects, such that in retinal vasculature, they depend on TNF
      alpha and subsequent induction of tie2 via the MEK/ERK pathway.

PMID- 16439713
TI  - The selective advantage of alpha1-antitrypsin deficiency.
AB  - The S- and Z-deficiency alleles of alpha1-antitrypsin are found in more than 20%
      of some white populations. This high gene frequency suggests that these mutations
      confer a selective advantage, but the biologic mechanism of this has remained
      obscure. It is now well recognized that the S and Z alleles result in a
      conformational transition within the alpha1-antitrypsin molecule and the
      formation of polymers that are retained within the endoplasmic reticulum of
      hepatocytes. Polymers of mutant alpha1-antitrypsin can also form within the
      alveoli and small airways of the lung where they may drive the inflammation that
      underlies emphysema in individuals with alpha1-antitrypsin deficiency. This local
      production of polymers by mutant S and Z alpha1-antitrypsin may have also
      provided protection against infectious disease in the preantibiotic era by
      focusing and amplifying the inflammatory response to limit invasive respiratory
      and gastrointestinal infection. It is only since the discovery of antibiotics,
      the widespread adoption of smoking, and increased longevity that these
      protective, proinflammatory properties of alpha1-antitrypsin mutants have become
      detrimental to cause the emphysema and systemic inflammatory diseases associated
      with alpha1-antitrypsin deficiency.

PMID- 16439714
TI  - Influence of airway pressure on genioglossus activity during sleep in normal
      children.
AB  - RATIONALE: Most children with obstructive sleep apnea are able to sustain stable
      breathing during portions of sleep, despite an anatomic predisposition toward
      airway collapse. This suggests that additional determinants of airway patency are
      active, such as neuromuscular compensation. OBJECTIVES/METHODS: Using a custom
      intraoral surface electrode to record pharyngeal dilator muscle activity (the
      genioglossus [EMGgg]), we evaluated the muscle, ventilatory, and arousal
      responses to negative-pressure challenges during sleep in 19 healthy control
      children. MEASUREMENTS AND MAIN RESULTS: In response to these challenges, we
      observed (1) marked variability in individual EMGgg responsiveness (peak EMGgg
      [mean+/-SD], 214+/-101% baseline), which was consistent within subjects; (2) a
      relationship between EMGgg activity and inspiratory flow and airway
      collapsibility; (3) reflex increases in flow (peak flow increase from challenge
      breaths 1-5 [mean+/-SD], 49+/-41% baseline) and respiratory rate often sufficient
      to sustain minute ventilation near baseline levels, without arousal; and (4)
      arousal threshold to be highest in stage 4, intermediate in stage 2, and lowest
      in REM sleep. CONCLUSIONS: Healthy children have wide variation in upper airway
      neuromuscular compensatory responses and arousal thresholds that could represent
      intermediate phenotypes affecting the expression of sleep apnea. Children with
      robust upper airway neuromuscular responsiveness, or a very high arousal
      threshold, may be able to sustain minute ventilation when challenged with
      negative airway pressure.

PMID- 16439715
TI  - Lung function decline and outcomes in an adult population.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is an important cause of
      morbidity and mortality. OBJECTIVES: To determine risk factors for and outcomes
      of rapid lung function decline in a cohort of adults in the United States.
      METHODS: We analyzed data from 15,536 adults aged 44-66 yr in the Atherosclerosis
      Risk in Communities study. We used Cox proportional hazard models to determine
      the risk of rapid lung function decline at 3 yr on mortality and COPD
      hospitalizations over the subsequent 8 yr. MEASUREMENTS AND MAIN RESULTS: Of
      those in the baseline cohort, 13,756 (88.5%) had spirometry at the Year 3 visit.
      The strongest risk factors for not having a follow-up spirometry were as follows:
      having Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3 or 4
      disease at baseline (adjusted odds ratio [OR] 2.8; 95% confidence interval [CI],
      2.1-3.8), being black (adjusted OR, 2.4; 95% CI, 2.1-2.7), and being a current
      smoker (adjusted OR, 1.8; 95% CI, 1.5-2.0). Participants with GOLD stage 3 or 4
      disease were also more likely to be in the most rapidly declining lung function
      quartile (adjusted OR, 3.7; 95% CI, 2.7-5.0). Overall, participants with the most
      rapidly declining lung function had a modestly increased risk of death (adjusted
      hazard ratio, 1.4; 95% CI, 1.2-1.7) and time to a COPD-related hospitalization
      (adjusted hazard ratio, 1.4; 95% CI, 1.2-1.8). CONCLUSION: Rapid lung function
      decline was independently associated with a modest increased risk of COPD
      hospitalizations and deaths.

PMID- 16439716
TI  - Statistical treatment of exacerbations in therapeutic trials of chronic
      obstructive pulmonary disease.
AB  - Randomized trials and a meta-analysis suggesting that inhaled corticosteroids
      reduce exacerbation rates in patients with chronic obstructive pulmonary disease
      (COPD) show major discrepancies that may be due to different approaches to data
      analysis. These trials used statistical techniques that were either weighted or
      unweighted for follow-up time, with p values and confidence intervals estimated
      with or without accounting for between-patient variability in exacerbation rates.
      We illustrate the validity of these methods using data from a cohort of 5,454
      patients with COPD structured to emulate a randomized trial. The "reference"
      group was defined as patients with a history of exacerbations before cohort entry
      (n=1,137), whereas the "treated" group included an equal number (n=1,137) of
      patients with no prior exacerbation. Random samples of 100 and 200 subjects were
      selected three times from each of two groups to further illustrate the
      variability in the findings. Exacerbations during follow-up were identified from
      prescriptions for systemic antibiotics. The correct rate ratio of 0.75 estimated
      by the weighted approach was underestimated as 0.57 by the unweighted approach.
      When the weighted approach did not, however, also account for between-patient
      variability, the p value was greatly underestimated (e.g., rate ratio, 0.79;
      p=0.0007 instead of p=0.12) and confidence intervals were much narrower than
      after properly accounting for this variability. In conclusion, the reports from
      randomized trials and the meta-analysis that inhaled corticosteroids reduce COPD
      exacerbation rates are the result of improper statistical analysis techniques.
      The only two studies that used the correct statistical approach found
      insignificant effects with these drugs.

PMID- 16439717
TI  - Antioxidant vitamin C improves endothelial function in obstructive sleep apnea.
AB  - RATIONALE: Obstructive sleep apnea (OSA) is associated with oxidative stress,
      endothelial dysfunction, and increased cardiovascular morbidity and mortality.
      OBJECTIVE: We tested the hypothesis that endothelial dysfunction in patients with
      OSA is linked to oxidative stress. METHODS: In the present study, we measured
      flow-mediated dilation (FMD) of the brachial artery by ultrasound in 10 otherwise
      healthy, untreated patients with OSA and 10 age-and sex-matched control subjects
      without sleep-disordered breathing before and after intravenous injection of the
      antioxidant vitamin C. The investigator performing the FMD measurements was
      blinded to the status of the patients. RESULTS: When compared with control
      subjects, baseline FMD was significantly reduced in the patients with OSA. After
      intravenous injection of 0.5 g vitamin C, vasoreactivity remained unchanged in
      the control subjects. In the patients with OSA, ascorbate led to an increase in
      FMD to a level comparable to that observed in the control group. CONCLUSION: The
      reduced endothelial-dependent vasodilation in untreated patients with OSA acutely
      improves by the free radical scavenger vitamin C. These results are in favor of
      oxidative stress being responsible for the endothelial dysfunction in OSA.
      Antioxidant strategies should be explored for the treatment of OSA-related
      cardiovascular disease.

PMID- 16439718
TI  - Protein profiles of bronchoalveolar lavage fluid from patients with pulmonary
      sarcoidosis.
AB  - BACKGROUND: Pulmonary sarcoidosis is a multisystem granulomatous disease with
      various clinical phenotypes. So far, there has been little information on protein
      patterns (PPs) of bronchoalveolar lavage fluid (BALF) from patients with
      sarcoidosis and no data are available on PPs in clinical disease subtypes.
      OBJECTIVES: To investigate the PP of BALF from patients with pulmonary
      sarcoidosis, to evaluate whether PPs reflect disease course as assessed by chest
      X-ray (CXR), and to compare PPs between patients with/without Lofgren's syndrome.
      METHODS: Surface-enhanced laser desorption/ionization-time-of-flight mass
      spectroscopy was applied to investigate PPs in unconcentrated BALF from 65
      patients (CXR stage I, n = 32; CXR stage II, n = 22, CXR stage III, n = 11) and
      23 healthy control subjects. The Mann-Whitney U test was used to detect
      differentially expressed protein peaks. After reversed-phase fractionation,
      peptide fingerprint mapping and immunodepletion were used to identify deregulated
      (up-regulated or down-regulated) proteins. RESULTS: Forty differentially
      expressed protein entities (2.75-185.62 kD) were detected in patients with
      pulmonary sarcoidosis versus control subjects (p < 0.05). Whereas 13 peaks (33%)
      were present across all CXR stages, 27 (67%) were specific for particular CXR
      stages. Comparison of PPs between CXR stage I patients with or without Lofgren's
      syndrome revealed 25 differentially expressed peaks. The total number of
      deregulated peaks and also of those associated with sarcoidosis as a whole were
      markedly lower in patients with Lofgren's syndrome in comparison with other
      sarcoid phenotypes. Human serum albumin, alpha1-antitrypsin, and protocadherin-2
      precursor were identified from sarcoidosis-associated PP. CONCLUSION: Surface
      enhanced laser desorption/ionization-time-of-flight mass spectroscopy enables
      determination of protein patterns in sarcoid BALF and allows detection of protein
      patterns linked to a particular disease course.

PMID- 16439719
TI  - Acinar structure in symptom-free adults by Helium-3 magnetic resonance.
AB  - RATIONALE: The apparent diffusion coefficient of hyperpolarized (3)He in the
      lungs has been shown to correlate directly in animal models with the peripheral
      airspace size and can detect changes in lung microstructure. OBJECTIVES: To study
      in vivo the (3)He apparent diffusion coefficient and to demonstrate its
      sensitivity to changes in lung morphometry as a result of aging, exposure to
      cigarette smoke, and lung inflation. METHODS: We assessed the variation in the
      diffusion of hyperpolarized (3)He gas in the lungs by magnetic resonance
      techniques. Spirometric lung volumes were recorded. MEASUREMENTS: We measured the
      dependence of (3)He diffusion on age and on reported cigarette smoke exposure in
      32 symptom-free adults. We also measured the dependence of the apparent diffusion
      coefficient on the degree of lung inflation. RESULTS: In healthy never-smokers,
      the apparent diffusion coefficient increased with age from 0.115 to 0.155 cm(2) .
      s(-1) at 20 and 70 yr, respectively, increased linearly with lung inflation and
      was independent of individual's lung size after correcting for age. For active
      and passive smokers, the apparent diffusion coefficient increased by up to 40%
      compared with never-smokers with mean values significantly higher (p=0.016 and
      p=0.0007, respectively). CONCLUSIONS: Peripheral airspace size increases with age
      and after exposure to smoke in healthy adults in agreement with previous
      histologic studies. We have confirmed in vivo that peripheral airspace size is
      independent of intersubject lung size.

PMID- 16439720
TI  - The effect of helium and oxygen on exercise performance in chronic obstructive
      pulmonary disease: a randomized crossover trial.
AB  - RATIONALE: Breathing supplemental oxygen reduces breathlessness during exercise
      in patients with chronic obstructive pulmonary disease (COPD). Replacing nitrogen
      with helium reduces expiratory flow resistance and may improve lung emptying.
      Combining these treatments should be independently effective. OBJECTIVES: Study
      the effect of changing oxygen or helium concentration in inspired gas during
      exercise in patients with stable COPD. METHODS: In 82 patients (mean age, 69.7
      yr; mean FEV(1), 42.6% predicted), we measured endurance shuttle walking
      distance, resting and exercise oxygen saturation, and end-exercise dyspnea (Borg
      scale) while patients breathed Heliox28 (72% He/28% O(2)), Heliox21 (79% He/21%
      O(2)), Oxygen28 (72% N(2)/28% O(2)), or medical air (79% N(2)/21% O(2)). Gases
      were administered using a randomized, blinded, crossover design via a face mask
      and an inspiratory demand valve. RESULTS: Breathing Heliox28 increased walking
      distance (mean+/-SD, 147+/-150 m) and reduced Borg score (-1.28+/-1.30) more than
      any other gas mixture. Heliox21 significantly increased walking distance (99+/
      101 m) and reduced dyspnea (Borg score, -0.76+/-0.77) compared with medical air.
      These changes were similar to those breathing Oxygen28. The effects of helium and
      oxygen in Heliox28 were independent. The increase in walking distance while
      breathing Heliox28 was inversely related to baseline FEV(1) breathing air.
      CONCLUSION: Reducing inspired gas density can improve exercise performance in
      COPD as much as increasing inspired oxygen. These effects can be combined as
      Heliox28 and are most evident in patients with more severe airflow obstruction.

PMID- 16439721
TI  - Phasic respiratory pharyngeal mechanics by magnetic resonance imaging in lean and
      obese zucker rats.
AB  - RATIONALE: Although obstructive sleep apnea is strongly associated with obesity,
      we have little understanding of how obesity may alter the mechanical properties
      of the pharynx and the role of obesity in the pathogenesis of sleep apnea.
      OBJECTIVES: The overall objective of this study was to determine the effect of
      obesity on pharyngeal airway size and pharyngeal wall tissue strain in lean and
      obese Zucker rats. METHODS: Respiratory-gated magnetic resonance imaging with
      noninvasive tissue tagging was performed in anesthetized, spontaneously breathing
      lean (n = 9) and obese (n = 9) Zucker rats. Images acquired during expiration and
      inspiration of the rostral, mid-, and caudal pharynx were analyzed for airway
      size and pharyngeal wall tissue strain, using planimetry, optical flow, and
      finite element analyses. Differences in cross-sectional airway area, lateral and
      anteroposterior airway diameters, and tissue strain (stretch, compression, and
      direction of stretch) in the lateral and ventral pharyngeal walls were compared
      by analysis of variance (significance at p < 0.05). MEASUREMENTS AND MAIN
      RESULTS: Compared with their lean littermates, obese rats had the following
      significant findings: reduced pharyngeal airway cross-sectional area during
      inspiration and expiration, smaller increases in airway area during inspiration,
      and decreased lateral airway dilation during inspiration. Tissue strain in the
      pharyngeal walls showed no significant differences between obese and lean rats.
      CONCLUSIONS: These findings suggest that obesity results in a mechanical
      abnormality that decreases pharyngeal airway size and prevents a normal airway
      response to a given change in pharyngeal wall tissue strain.

PMID- 16439723
TI  - Failure of NIV in acute asthma: case report and a word of caution.
AB  - Noninvasive ventilation (NIV) is the provision of ventilatory support without the
      need for an invasive airway, and has revolutionized the management of patients
      with diverse forms of respiratory failure. The advantages of NIV include improved
      patient comfort and reduced need for sedation, while avoiding the complications
      of endotracheal intubation, including upper airway trauma, sinusitis, otitis, and
      nosocomial pneumonia. In selected patients, NIV has also been shown to improve
      survival. The role of NIV in acute severe asthma is at best controversial. In
      this case report, we describe a patient with acute severe asthma who was
      initially managed and failed with NIV, and was successfully managed with invasive
      ventilation. We also review the pathophysiological mechanisms of benefit of NIV
      in acute severe asthma, and the current literature on the use of NIV in acute
      asthma. In conclusion, a trial of NIV in acute asthma may be justified in
      carefully selected and monitored patients who do not respond to initial medical
      therapy. However, as its role is not clear and as the condition of an asthmatic
      patient may deteriorate abruptly, extreme caution is advisable to recognize
      failure of NIV as in the case presented here. Facilities for immediate
      endotracheal intubation and next level of treatment should be readily available.

PMID- 16439722
TI  - A protective role for the fifth complement component (c5) in allergic airway
      disease.
AB  - RATIONALE: Reports from our laboratory, as well as those from others, have
      documented the importance of complement activation, the C3a anaphylatoxin, and
      its receptor, C3aR, in promoting Th2 effector functions in a mouse model of
      bronchopulmonary allergy. Although deficiency in the fifth complement component
      (C5) has been linked to enhanced airway hyperresponsiveness in mice, the
      contribution of C5 to other major biological hallmarks of asthma has not been
      evaluated. OBJECTIVE: Accordingly, congenic C5-sufficient and C5-deficient mice
      were subjected to a mouse model of bronchopulmonary allergy to assess the impact
      of C5 on pulmonary inflammation and Th2 effector functions in experimental
      asthma. METHODS AND MAIN RESULTS: In contrast to observations reported for C3-
      and C3aR-deficient animals, C5-deficient mice exhibited significantly increased
      airway hyperresponsiveness relative to wild-type congenic control mice after
      antigen challenge. Moreover, challenged C5-deficient mice had a 3.4-fold and 2.7
      fold increase in the levels of airway eosinophils and lung interleukin (IL)-4
      producing cells, respectively, compared with challenged wild-type mice.
      Consistent with the numbers of IL-4-producing cells, C5-deficient mice also had
      increased bronchoalveolar lavage levels of the Th2 cytokines IL-5 and IL-13 and
      elevated serum levels of total and antigen-specific IgE. CONCLUSIONS: These data
      indicate that C5 plays an important protective role in allergic lung disease by
      suppressing inflammatory responses and Th2 effector functions observed in this
      experimental model. The protection provided by the presence of C5 is likely
      mediated by C5a, suggesting that C5a may play a significant role in tempering
      inflammation in Th2-driven diseases such as asthma.

PMID- 16439724
TI  - Do we intervene inappropriately for ST elevation?
AB  - ST elevation on a 12 lead ECG is one of the cardinal features of acute myocardial
      infarction (AMI), yet it also occurs with other clinical conditions such as
      spontaneous pneumothorax. Three cases are presented, all of whom had chest pain
      and ST elevation. All had pneumothoraces yet only one had an AMI. Thrombolysis
      was administered to one patient. With the current pressure on "door-to-needle"
      times, emergency physicians should take care to differentiate between these
      entities.

PMID- 16439725
TI  - A left MCA territory infarction during intravenous recombinant tissue plasminogen
      activator therapy for right MCA territory ischaemic stroke.
AB  - An 81 year old man with a history of hypertension received intravenous
      recombinant tissue plasminogen activator (tPA) for right middle cerebral artery
      (MCA) infarction. He had not had stroke or arrhythmia previously. The initial
      National Institute of Health Stroke Scale (NIHSS) score was 8. However, a left
      MCA territory infarction developed 2 minutes after the full course of tPA therapy
      was completed, and 24 hours after tPA infusion, NIHSS score was 17. The
      subsequent magnetic resonance imaging scan confirmed an extensive left MCA
      territory infarction and a small right MCA territory infarction. Although the
      intracerebral haemorrhage after tPA therapy is relatively more common, tPA
      infusion may result in an ischaemic cerebral stroke in rare cases.

PMID- 16439726
TI  - Mediastinitis and retropharyngeal abscess following delayed diagnosis of glass
      ingestion.
AB  - Foreign body ingestion is a common occurrence in childhood. We report the outcome
      of an infant who swallowed a piece of glass. The absence of a foreign body on
      chest radiograph led to delayed diagnosis and then to the well documented
      complications of retropharyngeal abscess and mediastinitis. She was admitted to
      the paediatric intensive care unit a week after her initial presentation,
      subjected to multiple invasive and non-invasive procedures, and 6 weeks after her
      initial presentation to the accident and emergency department, was discharged
      back to her referring hospital having re-established oral feeds.

PMID- 16439727
TI  - Retained knife blade: an unusual cause for headache following massive alcohol
      intake.
AB  - Massive alcohol intake usually resolves in a banal headache. We report a case of
      a patient presenting with acute alcohol intoxication in which the ensuing
      "hangover" was due to a knife blade deeply retained in the brain parenchyma. This
      case underlines the unpredictability of retained foreign bodies without a high
      level of suspicion and a detailed description of the circumstances of admission.

PMID- 16439728
TI  - Magnetic resonance angiogram 3-D reconstruction in acute aortic transection.

PMID- 16439729
TI  - Painless aortic dissection with bilateral carotid involvement presenting with
      vertigo as the chief complaint.
AB  - A 63 year-old woman was admitted to the emergency department with vertigo,
      nausea, and vomiting. On arrival, she was fully oriented and cooperative. She
      denied any pain in her chest, neck, back, or abdomen. A bruit was heard on both
      sides of her neck. Cranial computed tomography (CT) revealed no abnormality,
      while thoracic CT disclosed dissection in the ascending aorta, aortic arch, and
      bilateral common carotid arteries. After several hours, the patient underwent
      vascular surgery. She had an uneventful course and was discharged without any
      sequelae after 10 days. Vertigo is a rare presentation of aortic dissection with
      carotid involvement. Elderly patients presented with vertigo and nausea/vomiting
      should be evaluated for the condition and carotid dissection should be ruled out.
      Carotid bruit may be a clue to the diagnosis.

PMID- 16439730
TI  - Cervical osteomyelitis associated with intravenous drug use.

PMID- 16439731
TI  - Paracolic echogenic mass in a man with lower abdominal pain. Is epiploic
      appendagitis more common than previously thought?

PMID- 16439732
TI  - Triage; evolution or extinction.

PMID- 16439733
TI  - A review of the use of propofol for procedural sedation in the emergency
      department.
AB  - Sedation for short but potentially painful procedures is often undertaken in the
      emergency department. The ideal sedative regimen should provide analgesia and
      anxiolysis with minimal side effects and cardiorespiratory depression and rapid
      recovery post-procedure. Propofol has found increasing popularity with
      anaesthetists for sedation in the operating theatre. This is a review of the
      current literature looking at the use of propofol for procedural sedation in the
      emergency department. A comprehensive literature search of Medline from 1966 to
      week 4 of 2005, Embase from 1980 to week 10 of 2005, and the Cochrane Library was
      carried out using the OVID interface. Eight articles were selected for review.
      The evidence suggests that propofol is both effective and safe to use in the
      emergency department. However, several of the papers reviewed used deep levels of
      sedation that are not recommended in the UK by non-anaesthetists.

PMID- 16439734
TI  - Investigating pulmonary embolism in the emergency department with lower limb
      plethysmography: the Manchester Investigation of Pulmonary Embolism Diagnosis
      (MIOPED) study.
AB  - OBJECTIVES: To measure the diagnostic accuracy of computerised strain gauge
      plethysmography in the diagnosis of pulmonary embolism (PE). METHODS: Two
      researchers prospectively recruited 425 patients with pleuritic chest pain
      presenting to the emergency department (ED). Lower limb computerised strain gauge
      plethysmography was performed in the ED. All patients underwent an independent
      reference standard diagnostic algorithm to establish the presence or absence of
      PE. A low modified Wells' clinical probability combined with a normal D-dimer
      excluded PE. All others required diagnostic imaging with PIOPED interpreted
      ventilation perfusion scanning and/or computerised tomography (CT) pulmonary
      angiography. Patients with a nondiagnostic CT had digital subtraction pulmonary
      angiography. All patients were followed up clinically for 3 months. RESULTS: The
      sensitivity of computerised strain gauge plethysmography was 33.3% (95%
      confidence interval (CI) 16.3 to 56.2%) and specificity 64.1% (95% CI 59.0 to
      68.8%). The negative likelihood ratio was 1.04 (95% CI 0.68 to 1.33) and positive
      likelihood ratio 0.93 (95% CI 0.45 to 1.60). CONCLUSIONS: Lower limb computerised
      strain gauge plethysmography does not aid in the diagnosis of PE.

PMID- 16439735
TI  - Anxiety disorder in patients with non-specific chest pain in the emergency
      setting.
AB  - OBJECTIVES: Many patients who have been discharged from the emergency department
      (ED) with a diagnosis of "non-specific chest pain" (NSCP) have anxiety disorder
      (AD), a commonly missed entity in acute care. The objective of this study was to
      delineate characteristic properties that could enhance recognition of AD in ED
      patients admitted with NSCP. METHODS: All patients between 18 and 65 years of age
      diagnosed with NSCP were enrolled. The Hospital Anxiety and Depression Scale
      (HADS) anxiety subscale was used as a screening test for AD. The patients with
      high HADS scores (> or = 10) were evaluated by a psychiatrist for AD. RESULTS: In
      total, 157 patients were enrolled in the study. HADS scores were found to be
      "high" (> or = 10) in 49 patients (31.2%). Patients with high HADS scores had a
      higher frequency of associated symptoms (p = 0.004). Dizziness or
      lightheadedness, chills or hot flushes, and fear of dying were found to have been
      reported more frequently by patients with high anxiety scores. Of the group with
      high score, 33 patients (67.3%) were interviewed by a psychiatrist, and 23
      (69.7%) of these patients were diagnosed with AD. Associated symptoms were
      described by 21 patients with AD (91.3%). Of those with AD, 18 (78.3%) had been
      previously admitted to the ED with chest pain. Atypical chest pain was described
      by 21 patients (91.3%). CONCLUSIONS: Physicians should always consider AD in
      patients presenting to the ED with chest pain after ruling out organic aetiology.
      Patients' definition of atypical pain, recurrent admissions to ED, and presence
      of associated symptoms such as dizziness, chills or hot flushes, and fear of
      dying could aid in considering AD.

PMID- 16439736
TI  - An audit of advice on fitness to drive during accident and emergency department
      attendance.
AB  - INTRODUCTION: Large numbers of patients attending accident and emergency (A&E)
      departments drive to and from the consultation. This audit set out to examine if
      patients attending A&E were advised about their fitness to drive. METHOD: The
      authors carried out a retrospective audit over a one month period. The Driver and
      Vehicle Licensing Authority (DVLA) booklet "At a glance guide to the current
      medical standards of fitness to drive" was used to derive a list of conditions
      that require driving restrictions. Any condition within these guidelines was
      audited. If the patient was discharged and diagnosed as having a condition
      requiring the patient to cease driving, the notes were scrutinised for any
      evidence that the doctor had given advice about driving. RESULTS: A total of 337
      patients were discharged with conditions which may have required some
      restrictions to driving; 332 sets of notes were available. Twenty two patients
      needed restrictions to be placed on their driving. Only one patient had any
      documented evidence of the examining doctor informing them of restrictions to be
      placed on driving. CONCLUSIONS: The study provides clear evidence that patients
      were not being informed about their fitness to drive following consultation in
      the authors' A&E department. Previous studies have shown that doctors' knowledge
      on driving restrictions is poor. Further education is needed for A&E doctors and
      patient information leaflets should be provided to explain the restrictions
      placed on a driver's licence if they have certain illnesses.

PMID- 16439737
TI  - Clinical supervision in the emergency department: a critical incident study.
AB  - OBJECTIVES: To identify the key features of effective clinical supervision in the
      emergency department (ED) from the perspectives of enthusiastic consultants and
      specialist registrars. To highlight the importance of clinical supervision within
      emergency medicine, and identify obstructions to its occurrence in everyday
      practice. METHODS: A critical incident study was undertaken consisting of
      structured interviews, conducted by telephone or in person, with 18 consultants
      and higher level trainees selected for their interest in supervision. RESULTS:
      Direct clinical supervision of key practical skills and patient management steps
      was considered to be of paramount importance in providing quality patient care
      and significantly enhancing professional confidence. The adequacy of supervision
      varied depending upon patient presentation. Trainees were concerned with the
      competence and skills of their supervisor; consultants were concerned with wider
      systemic constraints upon the provision of adequate supervision to juniors.
      CONCLUSIONS: The value of supervision extends to all patient presentations in the
      ED. The study raised questions concerning the appropriate attitudes and
      qualifications for supervisors. Protected supervisory time for those with
      trainees is mandatory, and must be incorporated within ED consultant job
      planning.

PMID- 16439738
TI  - NICE guideline for the management of head injury: an audit demonstrating its
      impact on a district general hospital, with a cost analysis for England and
      Wales.
AB  - OBJECTIVES: To answer concerns related to implementation of the National
      Institute for Clinical Excellence (NICE) guideline on the management of head
      injury by determining the impact on the workload of a district general hospital.
      Increased computed tomography (CT) was of particular concern (cost, radiation
      risk, and delivery constraints). METHOD: Retrospective audit of all patients
      attending the hospital's emergency department with a head injury over a three
      month period. Any reattendees for the same head injury episode were excluded but
      the need for CT was recorded. Case notes and electronic records were reviewed to
      determine whether the CT head or skull radiograph (SXR) was indicated in line
      with the NICE guideline. The workload was compared with an identical audit
      performed before the implementation of the NICE guideline. RESULTS: Of 17 472
      patients attending the ED in 2004, 472 had a head injury. CT scan was indicated
      in 36, a significant increase from 2003 (p < 0.001). No SXR was indicated but two
      were performed, a significant decrease (p < 0.001). The admission rate was
      unaltered. The positive predictive value of NICE was 17.1% compared with 25% (p =
      not significant) for the authors' pre-NICE departmental guideline. CONCLUSIONS:
      This department has seen an increase in CT head requests since the implementation
      of the NICE guideline. This costs an extra 15,000 pounds sterling per 100 head
      injuries annually for this department, with an estimated 51.7 million pounds
      sterling burden for England and Wales. Further evaluation is required as there
      were only nine brain injuries in this audit population.

PMID- 16439739
TI  - Whiplash associated disorder: incidence and natural history over the first month
      for patients presenting to a UK emergency department.
AB  - OBJECTIVES: To describe the epidemiology, process of care, and outcomes at 4-6
      weeks after injury among patients with whiplash associated disorder attending a
      UK emergency department. METHODS: All patients presenting during the study period
      with neck pain following a road traffic accident who met the inclusion criteria
      were assessed. Patients were followed up with a telephone interview at 4-6 weeks
      after attendance using the Neck Disability Index (NDI). The patient's general
      practitioner (GP) was contacted post attendance to ascertain subsequent
      healthcare use. RESULTS: A total of 200 patients were recruited to the study, of
      which 30 were lost to follow up. Four variables, midline tenderness (p = 0.008;
      95% CI 0.9 to 6.1), x ray request (p = 0.004; 0.9 to 6.1), wearing a seat belt (p
      = 0.038; 0.2 to 6.2), and having seen their GP post injury (p = 0.001; CI -10.5
      to 6.6), were found to be associated with a higher NDI score at follow up.
      Significant correlation was identified with a high pain score and an increasing
      age of patient and high NDI scores. No correlation was found between the impact
      speed, speed of vehicle struck, or time since incident with the NDI. Two thirds
      of patients had some disability at 4-6 weeks after injury; 91 patients (54.5%)
      saw their GP in the intervening period between attending the department and
      telephone follow up, and 87/170 patients had no idea about their prognosis.
      CONCLUSIONS: This study identifies that there is significant disability
      associated with whiplash associated disorder. Clear prognostic information would
      be a useful development.

PMID- 16439741
TI  - Outpatient diagnosis of pulmonary embolism: the MIOPED (Manchester Investigation
      Of Pulmonary Embolism Diagnosis) study.
AB  - BACKGROUND AND OBJECTIVES: Pleuritic chest pain, a symptom of pulmonary embolism,
      is a common presenting symptom in the emergency department. The aim of this study
      was to validate an algorithm for the diagnosis of pulmonary embolism in emergency
      department patients with pleuritic chest pain. METHODS: This was a prospective,
      diagnostic cohort study conducted in a large UK city centre emergency department.
      A total of 425 patients with pleuritic chest pain presenting to the emergency
      department between February 2002 and June 2003 were recruited. Patients scoring a
      low modified Wells clinical probability of pulmonary embolism, who had a normal
      latex agglutination D-dimer, were discharged. All others followed a diagnostic
      imaging protocol to exclude and diagnose pulmonary embolism using PIOPED
      interpreted ventilation-perfusion scanning, CT pulmonary angiography, and digital
      subtraction pulmonary angiography. All patients were followed up for three months
      for evidence of pulmonary embolism or deep vein thrombosis. An independent
      adjudication committee reviewed all deaths. RESULTS: A total of 408 patients
      completed the diagnostic algorithm; 86.5% (353/408) were investigated as
      outpatients, 5.4% (22/408) were diagnosed as having pulmonary embolism, and 98.8%
      (403/408) were followed up for three months. Of the 381 patients without
      pulmonary embolism who completed follow up, the incidence of thromboembolic
      disease was 0.8% (95% CI 0.3% to 2.3%): two patients had pulmonary embolism and
      one had a deep vein thrombosis. CONCLUSIONS: The MIOPED (Manchester Investigation
      Of Pulmonary Embolism Diagnosis) diagnostic protocol can safely exclude pulmonary
      embolism in outpatients with pleuritic chest pain.

PMID- 16439740
TI  - Selective inhibition of polymorphonuclear neutrophils by resuscitative
      concentration of hypertonic saline.
AB  - OBJECTIVES: This study investigated the effect of hypertonic saline on the role
      of polymorphonuclear neutrophils (PMNs) in the inflammatory response and the
      effect of hypertonic saline infused at different phases in relation to an
      inflammatory stimulus. MATERIALS AND METHODS: PMNs were isolated from peripheral
      blood of healthy volunteers (Boyum's method) and cultured in three different
      media ([Na+] = 140 mmol/l, 180 mmol/l, and 200 mmol/l). PMNs were then stimulated
      with fMLP (N-formyl-methionyl-leucyl-phenylalanine) and H2O2 synthesis was
      quantified by flow cytometry at 5, 30, 60, 120, and 180 minutes. PMNs were
      treated with hypertonic saline before, simultaneously with, and after fMLP
      stimulation, and H2O2 synthesis quantified again. RESULTS: H2O2 synthesis was two
      or three times higher in fMLP stimulated than in non-stimulated PMNs, and it
      reached maximum level at 120 minutes. In the absence of fMLP stimulation, there
      was no significant difference between control and hypertonic saline with regard
      to activity of H2O2 synthesis. In the presence of fMLP stimulation, H2O2
      synthesis significantly decreased in PMNs treated with hypertonic saline. There
      was no significant difference between the two hypertonic saline solutions ([Na+]
      = 180 mmol/l and 200 mmol/l) with regard to H2O2 synthesis. However, H2O2
      synthesis decreased in PMNs treated with hypertonic saline before and
      simultaneously with fMLP stimulation, but was not significantly decreased in the
      cells treated with hypertonic saline after fMLP stimulation. CONCLUSIONS:
      Hypertonic saline appears to decrease H2O2 in stimulated neutrophils. This may be
      a further beneficial role of hypertonic saline when used clinically as an early
      resuscitation fluid.

PMID- 16439742
TI  - Standards for head injury management in acute hospitals: evidence from the six
      million population of the Eastern region.
AB  - OBJECTIVES: To develop standards of care for head injury and thereby identify and
      prioritize areas of the service needing development; to report the findings from
      a survey of compliance with such standards in the Eastern region of UK. METHODS:
      The standards were collaboratively developed through an inclusive and iterative
      process of regional surveys, multidisciplinary conferences, and working groups,
      following a method similar to that used by the Society of British Neurological
      Surgeons. The standards cover seven topics relating to all aspects of service
      delivery, with standards within each objective. Each standard has been designated
      a priority level (A, B, or C). The standards were piloted using a self-assessment
      questionnaire, completed by all 20 hospitals of the Eastern region. RESULTS: Full
      compliance was 36% and a further 30% of standards were partially met across the
      region, with some areas of service delivery better than others. Seventy eight per
      cent of level A standards were either fully or partially met. Results were better
      in the north of the region compared with the south. CONCLUSION: A survey of
      compliance with the head injury standards indicate that, with their whole systems
      approach and subject to further refinement, they are a useful method for
      identifying deficiencies in service provision and monitoring for quality of care
      both within organisations and regionally.

PMID- 16439743
TI  - Ibutilide for treatment of atrial fibrillation in the emergency department.
AB  - The purpose of this study was to assess the efficacy and safety of ibutilide, a
      class III antiarrhythmic drug, for acute treatment of atrial fibrillation (AF) in
      the emergency department (ED) setting. A retrospective analysis was done
      reviewing all patients with AF who received ibutilide in the ED in a university
      hospital setting. A total of 22 patients received ibutilide. Another 24 patients
      who received rate control drugs only served as a control group. Of the 22
      patients who received ibutilide, 14 (64%) converted to sinus rhythm. The mean
      (SD) rate of AF was 137 (24) bpm and the mean QTc interval immediately after
      conversion to sinus rhythm was 420 (28) ms. There were no complications. In the
      rate control group 7 patients (29%) converted to sinus rhythm (p<0.05, compared
      with ibutilide). The mean rate of AF was 126 (26) bpm (p = ns, compared with
      ibutilide) and the mean QTc interval in those who converted was 377 (28) ms
      (p<0.05, compared with ibutilide). One patient developed severe bradycardia.
      Ibutilide is effective for conversion of recent onset AF in patients presenting
      to the ED and there is a low rate of complications from ibutilide in this
      setting.

PMID- 16439744
TI  - Primary headache disorder in the emergency department: perspective from a general
      neurology outpatient clinic.
AB  - Over a six month period, 22% of patients with headache seen in general neurology
      outpatient clinics reported prior attendance at an emergency department because
      of their headache; 9% of the headache cohort had been admitted to hospital. All
      had primary headache disorders according to International Headache Society
      diagnostic criteria. Improved primary care services for headache patients are
      required to reduce the burden of primary headache disorders seen in emergency
      departments.

PMID- 16439745
TI  - Skimboarding: a new danger in the surf?
AB  - Skimboarding is an increasingly popular activity on the beach. Over a six week
      period we saw 10 patients with fractures or dislocations, half of whom required
      operative intervention. The majority (80%) were of the lower limb, some of which
      were severe.

PMID- 16439746
TI  - Best evidence topic report. Urine dipsticks in screening for diabetes mellitus.

PMID- 16439747
TI  - Best evidence topic report. Chest drains in traumatic occult pneumothorax.

PMID- 16439750
TI  - Best evidence topic report. Administration of steroids in acute exacerbations of
      COPD.

PMID- 16439749
TI  - Best evidence topic report. Clopidogrel plus aspirin or aspirin alone in unstable
      angina.

PMID- 16439751
TI  - Oxygen: kill or cure? Prehospital hyperoxia in the COPD patient.
AB  - High concentration oxygen therapy has long been a mainstay of prehospital
      treatment. Guidelines for its administration have for many years also cautioned
      its use with patients with chronic obstructive pulmonary disease (COPD).
      Successive guidelines and prehospital textbooks have advocated the use of 28%
      oxygen masks and re-emphasised the importance of the dangers of hyperoxia, often
      drawing upon the classic theory of hypoxic drive. Despite this, the reality
      remains that ambulance crews have tended to overoxygenate such patients. One
      study demonstrated that 80% of patients sampled with acute exacerbation of their
      COPD received oxygen in excess of 28% from the ambulance crew. Is this a worrying
      development or a reassuring sign that prehospital providers are rightly more
      concerned about the dangers of hypoxia than hyperoxia? And if the guidelines are
      right, then how are the hearts and minds of ambulance paramedics and technicians
      won?

PMID- 16439752
TI  - A case of dextrocardiac ventricular fibrillation arrest.
AB  - Successful defibrillation of a patient with dextrocardia using conventional
      anterolateral paddle positions raises doubts about the necessity to place paddles
      in the exact recommended positions. Evidence found relates either to volunteers
      in a laboratory setting or to defibrillation of atrial arrhythmias. The
      conclusion is that there is no published difference either in transthoracic
      impedance or in success of defibrillation between anteroposterior and
      anterolateral paddle positions. In the absence of any evidence for an ideal
      apical paddle position in the standard anterolateral defibrillation of
      ventricular arrhythmias, the emphasis in ALS and resuscitation guidelines on
      "correct" positioning seems misplaced, and, by adding unnecessary information,
      may hinder learning the skill of defibrillation. Early defibrillation is crucial
      to successful recovery from cardiac arrest and anything that delays cardioversion
      should be avoided. The limited evidence suggests that the exact position of the
      paddles does not matter. The time taken to find the "correct" position is time
      wasted and it may instead be preferable to teach people merely to place the
      apical paddle to the left of the nipple in the midaxillary line.

PMID- 16439753
TI  - The Cape Triage Score: a new triage system South Africa. Proposal from the Cape
      Triage Group.
AB  - The Cape Triage Group (CTG) convened with the intention of producing a triage
      system for the Western Cape, and eventually South Africa. The group includes in
      hospital and prehospital staff from varied backgrounds. The CTG triage protocol
      is termed the Cape Triage Score (CTG), and has been developed by a multi
      disciplinary panel, through best available evidence and expert opinion. The CTS
      has been validated in several studies, and was launched across the Western Cape
      on 1 January 2006. The CTG would value feedback from readers of this journal, as
      part of the ongoing monitoring and evaluation process.

PMID- 16439754
TI  - Evolution of triage systems.
AB  - The French word "trier", the origin of the word "triage", was originally applied
      to a process of sorting, probably around 1792, by Baron Dominique Jean Larrey,
      Surgeon in Chief to Napoleon's Imperial Guard. Larrey was credited with designing
      a flying ambulance: the Ambulance Volante. Baron Francois Percy also contributed
      to the organisation of a care system for the ongoing management of casualties.
      Out of the French Service de Sante, not only emerged the concept of triage, but
      the organisational structure necessary to handle the growing number of casualties
      in modern warfare.

PMID- 16439755
TI  - Case of the month: Complete transection of the trachea and oesophagus in a 10
      year old child: a difficult airway problem.

PMID- 16439757
TI  - Auditory and visual prompts during cardiopulmonary resuscitation in the emergency
      department.

PMID- 16439758
TI  - ATLS: there are alternatives.

PMID- 16439759
TI  - NICE head injury guidelines--expensive? Yes, but what are the alternatives?

PMID- 16439760
TI  - A nation divided.

PMID- 16439761
TI  - Handheld echocardiography--core skill for emergency physicians or another
      expensive course?

PMID- 16439762
TI  - Steroids for meningitis in the Emergency Department?

PMID- 16439763
TI  - Use of Flumazenil in benzodiazepine overdose.

PMID- 16439764
TI  - Complications following attempted rapid sequence intubation.

PMID- 16439765
TI  - Gluten-free diet: the medical and nutrition management of celiac disease.
AB  - Celiac disease (CD) is a chronic disease causing inflammation of the proximal
      small intestine that occurs in genetically predisposed individuals when they eat
      gluten, which is the storage protein in wheat, barley, and rye. The disease
      injury usually resolves when gluten is excluded from the diet. Although the
      injury will heal, the reaction to gluten is permanent and will recur with the
      reintroduction of gluten. The condition is surprisingly common, affecting as many
      as 1% of white populations. The consequences of the disease are predominantly
      those of malnutrition due to maldigestion and malabsorption, such as diarrhea,
      weight loss, and anemia. Symptoms caused by inflammation of the small intestine
      are also common. CD, although it is common and its pathology is well understood,
      frequently goes undiagnosed, probably because of the nonspecific or vague nature
      of many of the symptoms that occur. The cornerstone of treatment for CD is
      elimination of gluten from the diet. In most patients diagnosed with CD, a strict
      gluten-free diet (GFD) alone should result in complete symptomatic and histologic
      resolution of the disease and reduce risk of complications. Noncompliance with
      diet is the leading cause of failure to respond in patients with CD. For these
      reasons, thorough assessment and counseling at the time of diagnosis and ongoing
      care are crucial. In this article, we address briefly what is known about the
      pathogenesis and diagnosis of CD and address its treatment in detail.

PMID- 16439766
TI  - Diagnosis and management of adult patients with chronic intestinal
      pseudoobstruction.
AB  - Chronic intestinal pseudoobstruction (CIP) is a motility syndrome that presents
      with symptoms and signs of intestinal obstruction and radiographic evidence of
      dilated bowels, but no anatomic obstruction can be found. It primarily is a
      disorder of small bowel motility, but it can occur anywhere in the
      gastrointestinal tract. This review will focus on the diagnosis and treatment of
      adult patients with CIP. The clinical presentation of CIP is variable, and its
      incidence is rare. It is a disorder with a multitude of etiologies, many of which
      are poorly understood. To properly manage the patient, clinicians should be aware
      of the various symptoms, signs, and systemic diseases that are associated with
      CIP. Diagnostic studies are needed to confirm the diagnosis, identify the
      etiology, and search for coexisting motility dysfunction. The management goals of
      CIP are to restore proper nutrition and fluid balance, relieve symptoms, improve
      intestinal motility, and treat complications.

PMID- 16439767
TI  - Nutrition aspects of gastroparesis and therapies for drug-refractory patients.
AB  - Gastroparesis, broadly defined as disordered gastric emptying, is a commonly
      encountered clinical problem. Nutrition problems frequently occur in
      gastroparesis, primarily due to inadequate oral intake but also due to losses
      from vomiting or diarrhea. Treatment of gastroparesis may include dietary
      modification with or without medication. Some patients require supplementation
      with either enteral or parenteral nutrition for survival. However, many patients
      with gastroparesis are drug-refractory and invariably do not do well with enteral
      or parenteral access. Historically, these patients have been without effective
      therapeutic options. The development of gastrointestinal electrical stimulation
      has allowed many with drug-refractory gastroparesis to be treated successfully.
      Enteric electrical stimulation for gastroparesis often corrects many of the
      nutrition abnormalities, along with improving symptoms and quality of life and
      reducing costs; for some categories of patients, it may improve survival rates.

PMID- 16439768
TI  - Nutrition management of chronic diarrhea and malabsorption.
AB  - Diet often is blamed for digestive symptoms, particularly diarrhea, and patients
      with diarrhea and malabsorption usually request guidance about what to eat. Food
      induced symptoms are very common. Although many recommendations have been made
      for dietary management in diarrheal diseases, there is little supportive evidence
      for efficacy for any of them. Knowledge of gastrointestinal physiology and the
      physiologic effects of foods can be used to design a dietary program for
      individual patients. Coordination of diet with drug therapy is an important part
      of a comprehensive treatment plan for these patients.

PMID- 16439769
TI  - Acute complications associated with bedside placement of feeding tubes.
AB  - Several types of feeding tubes can be placed at a patient's bedside; examples
      include nasogastric, nasointestinal, gastrostomy, and jejunostomy tubes.
      Nasoenteral tubes can be placed blindly at bedside or with the assistance of
      placement devices. Nasoenteric tubes can also be placed via fluoroscopy and
      endoscopy. Gastrostomy and jejunostomy tubes can be placed using endoscopic
      techniques. This paper will describe the indications and contraindications for
      different types of tubes that can be placed at the bedside and complications
      associated with tube placement. Complications associated with nasoenteral tubes
      include inadvertent malpositioning of the tube, epistaxis, sinusitis, inadvertent
      tube removal, tube clogging, tube-feeding-associated diarrhea, and aspiration
      pneumonia. Complications from percutaneous gastrostomy and jejunostomy tube
      placements include procedure-related mishaps, site infection, leakage, buried
      bumper syndrome, tube malfunction, and inadvertent removal. These complications
      will be reviewed, along with a discussion of incidence, cause, treatment, and
      prevention approaches.

PMID- 16439770
TI  - Techniques to prevent central venous catheter infections: products, research, and
      recommendations.
AB  - Central venous catheters (CVCs) are commonly used to deliver a variety of
      therapies such as chemotherapy and parenteral nutrition. It is well known that
      there are complications associated with CVCs; a major complication is catheter
      related bloodstream infection (CRBSI). Many strategies exist to prevent CVC
      complications and CRBSI. This paper will focus on the fight against CRBSI using 3
      products at the catheter insertion site: 2% chlorhexidine, BioPatch, and
      transparent split dressings. Lists of key recommendations from national
      organizations for infection prevention are included.

PMID- 16439771
TI  - Nutrition support teams: an evidence-based practice.
AB  - With the development of specialized nutrition support, an interdisciplinary
      approach was essential to translating this medical breakthrough from the
      laboratory to the bedside. As this new innovation was adopted, interdisciplinary
      nutrition support teams were created to optimize the effectiveness and safety of
      this therapy. The impact of standardization and the use of an interdisciplinary
      team to provide specialized nutrition support have been shown to improve outcomes
      and safety and to have a positive financial impact on healthcare institutions.
      Yet many hospitals do not have nutrition support teams, and the numbers that do
      may have decreased. To be effective, nutrition support teams need to practice at
      an evidence-based level and measure their performance. Nutrition support teams
      include many of the components of the healthcare delivery system that are
      advocated for the future, and nutrition support teams should be encouraged as the
      preferred system of providing specialized nutrition support.

PMID- 16439772
TI  - The origins of cachexia in acute and chronic inflammatory diseases.
AB  - The term cachexia originates from the Greek root kakos hexis, which translates
      into "bad condition," recognized for centuries as a progressive deterioration of
      body habitus. Cachexia is commonly associated with a number of disease states,
      including acute inflammatory processes associated with critical illness and
      chronic inflammatory diseases, such as cancer, congestive heart failure, chronic
      obstructive pulmonary disease, and human immunodeficiency virus infection.
      Cachexia is responsible for the deaths of 10%-22% of all patients with cancer and
      approximately 15% of the trauma deaths that occur from sepsis-induced organ
      dysfunction and malnutrition days to weeks after the initial traumatic event. The
      abnormalities associated with cachexia include anorexia, weight loss, a
      preferential loss of somatic muscle and fat mass, altered hepatic glucose and
      lipid metabolism, and anemia. Anorexia alone cannot fully explain the development
      of cachexia; metabolic alterations in carbohydrate, lipid, and protein metabolism
      contribute to the severe tissue losses. Despite significant advances in our
      understanding of specific disease processes, the mechanisms leading to cachexia
      remain unclear and multifactorial. Although complex, increasing evidence from
      both animal models and clinical studies suggests that an inflammatory response,
      mediated in part by a dysregulated production of proinflammatory cytokines, plays
      a role in the genesis of cachexia, associated with both critical illness and
      chronic inflammatory diseases. These cytokines are further thought to induce an
      acute phase protein response (APR) and produce the alterations in lipid and
      carbohydrate metabolism identified as crucial markers of acute inflammation in
      states of malignancy and critical illness. Although much is still unknown about
      the etiology of cachexia, there is growing appreciation that cachexia represents
      the endproduct of an inappropriate interplay between multiple cytokines,
      neuropeptides, classic stress hormones, and intermediary substrate metabolism.

PMID- 16439773
TI  - Guidelines for the use of orexigenic drugs in long-term care.
AB  - Undernutrition is defined as a state induced by nutrient deficiency that may be
      improved solely by administration of nutrients. By this definition, provision of
      adequate protein and energy sources should reverse the clinical presentation and
      correct the problem. However, a large number of patients who seem to be
      undernourished fail to respond to refeeding. A developing understanding of the
      acute-phase inflammatory response to illness and the role of cytokines in the
      pathophysiology of chronic illness has challenged the current diagnostic paradigm
      of undernutrition. In the presence of adequate food, weight loss is most often
      due to cytokine-associated cachexia and anorexia. Failure of appetite, or
      anorexia, may play a role in involuntary weight loss. Intervention for
      involuntary weight loss should aim first at the provision of adequate calories
      and protein, often in the form of high-density nutrition supplements. However,
      cytokine-mediated cachexia is remarkably resistant to hypercaloric feeding. With
      continued weight loss, the use of an orexigenic drug should be considered.
      Orexigenic drugs have been demonstrated to improve appetite and produce weight
      gain. The mechanism is unknown but may relate to suppression of proinflammatory
      cytokines. General guidelines for the use of orexigenic agents are presented.
      Although much work remains to be done, anticytokine drugs seem to be a promising
      avenue for the treatment of involuntary weight loss.

PMID- 16439774
TI  - A soluble ATP-dependent proteolytic system is responsible for protein
      degradation.

PMID- 16439775
TI  - Standards for specialized nutrition support for adult residents of long-term care
      facilities.

PMID- 16439776
TI  - Galactoceles mimicking suspicious solid masses on sonography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the sonographic appearance
      of a galactocele that can sonographically mimic a suspicious solid mass and to
      differentiate between a galactocele and a solid mass. METHODS: From September
      2002 to February 2004, 33 galactoceles classified as Breast Imaging Reporting and
      Data System category 4 were included. They were all confirmed by sonographically
      guided core biopsies. Their sonographic imaging and clinical findings were
      reviewed retrospectively. RESULTS: The lesions had a round or irregular shape in
      26 patients (78.8%), a noncircumscribed margin in 31 (93.9%), a nonparallel
      orientation in 22 (66%), and posterior shadowing in 13 (39.4%). Twenty-five
      nodules (75.8%) had internal hypoechogenicity or mixed echogenicity. Twenty-nine
      (87.9%) of 33 lesions showed a relatively sharp convex echogenic rim on the
      anterior or posterior wall. CONCLUSIONS: Galactoceles have various sonographic
      findings, many of which are similar to those of suspicious solid breast masses.
      However, there is a tendency for a galactocele to appear as a small, round
      hypoechoic nodule with an indistinct or microlobulated margin and mild posterior
      shadowing. It is helpful to search for a partial anterior or posterior echogenic
      rim to identify a galactocele.

PMID- 16439777
TI  - Doppler color flow analysis of the uterine arteries before and after intrauterine
      device insertion: a prospective study.
AB  - OBJECTIVE: An intrauterine device (IUD) is one of the most frequently used
      methods of birth control around the world. Although a relationship between its
      use and menstrual disorders has been well documented, only a few studies have
      tried to show whether there are any vascular modifications. The aim of our study
      was to evaluate the influence of an IUD on uterine artery blood flow using
      Doppler assessment. METHODS: A total of 100 patients selected for IUD use were
      prospectively evaluated with Doppler analysis before and 30 days after insertion.
      The resistive index (RI) and pulsatility index (PI) were used to evaluate uterine
      artery vascular resistance. Patients were allocated in 2 groups according to
      whether they were (group 2) or were not (group 1) lactating. RESULTS: The PI and
      RI of the patients in groups 1 and 2 before and after IUD insertion were not
      statistically significantly different (P = .298 and .23). When we compared
      uterine artery blood flow indices before and after IUD insertion for groups 1 and
      2 separately, we observed in group 1 that the mean +/- SD PI values were 2.45 +/-
      0.62 and 2.55 +/- 0.55 (P = .38) and the RI values were 0.87 +/- 0.08 and 0.87 +/
      0.06 (P = .88) before and after IUD insertion, respectively. In group 2, the PI
      values were 2.31 +/- 0.55 and 2.37 +/- 0.69 (P = .68) and the RI values were 0.85
      +/- 0.07 and 0.86 +/- 0.07 (P = .44) before and after IUD insertion. Finally, we
      used the mean blood flow indices of the uterine arteries of all patients to
      compare the effect of IUD insertion. Results were also not statistically
      significant when we compared PI and RI before and after IUD insertion.
      CONCLUSIONS: The presence of an IUD does not interfere with the vascular
      resistance of the uterine arteries that can be shown by Doppler flow assessments
      1 month after insertion.

PMID- 16439778
TI  - Reproducibility of endometrial vascular patterns in endometrial disease as
      assessed by transvaginal power Doppler sonography in women with postmenopausal
      bleeding.
AB  - OBJECTIVE: The purpose of this study was to assess the intraobserver and
      interobserver agreement for identifying different endometrial vascular patterns
      using power Doppler sonography in women with postmenopausal bleeding and a
      thickened endometrium. METHODS: Digitally stored sonographic images from a random
      sample of 65 patients with postmenopausal bleeding and a thick endometrium (>5
      mm) on B-mode sonography and evaluated by transvaginal power Doppler sonography
      for assessment of endometrial blood flow mapping were evaluated by 5 different
      examiners with different levels of expertise in Doppler sonography. Intraobserver
      and interobserver agreement according to the level of experience were assessed by
      calculating the kappa index. RESULTS: Intraobserver agreement was good or very
      good for all experienced examiners (kappa = 0.78-0.96) and moderate (kappa =
      0.52) for the inexperienced examiner. Interobserver agreement was moderate among
      all experienced examiners (kappa = 0.45-0.80). The inexperienced examiner showed
      fair or moderate interobserver agreement (kappa = 0.32-0.45). CONCLUSIONS: Our
      results indicate that endometrial blood flow mapping using transvaginal power
      Doppler sonography is acceptably reproducible. More experience was associated
      with better intraobserver and interobserver agreement.

PMID- 16439779
TI  - Improving the efficiency of gynecologic sonography with 3-dimensional volumes: a
      pilot study.
AB  - OBJECTIVE: The purpose of this study was to determine whether 3-dimensional (3D)
      sonography can provide a rapid, efficient, and accurate way to do a transvaginal
      gynecologic scan compared with traditional 2-dimensional (2D) sonography.
      METHODS: Thirty-five consecutive patients who underwent gynecologic sonography
      formed the study cohort. After a standard 2D transvaginal scan was done,
      including measurements of the endometrium and abnormalities, 4 volume
      acquisitions were obtained, encompassing the uterus (2 volumes) and the ovaries.
      These volumes were reviewed offline without any patient information. Endometrium
      and other measurements were performed on the volumes. The 2D and 3D results were
      compared by paired t tests. RESULTS: The mean time needed for the standard 2D
      scan was 2.6 minutes compared with 1.07 minutes for the 3D volume acquisitions.
      The mean time for the reconstruction, measurement, and interpretation of the
      volumes offline was 1.19 minutes. The mean time for the entire 3D examination
      (both parts) was 2.26 minutes (P = .047, comparing 2D with total 3D). There was
      no significant difference between the measurements of the endometrium, fibroids,
      and ovarian cysts when comparing 2D and reconstructed 3D images. Two-dimensional
      and 3D sonography differed little in their ability to identify the organs and the
      abnormalities on the scans. CONCLUSIONS: This study shows that a complete
      transvaginal gynecologic examination can be done in 1.07 minutes of scan time and
      interpreted offline in an additional 1.19 minutes. The 35 cases were scanned and
      interpreted with the use of 3D sonography in 79.17 minutes total compared with
      91.46 minutes of 2D scan time (P = .047). The accuracy of the scan was similar
      for both techniques.

PMID- 16439780
TI  - Early fetal echocardiography: heart biometry and visualization of cardiac
      structures between 10 and 15 weeks' gestation.
AB  - OBJECTIVE: The purpose of this prospective cross-sectional study was to compile
      normative data about biometry of the fetal heart and great vessels between 10 and
      15 weeks in 123 normal singleton pregnancies. Additionally, we investigated the
      different methods and the optimal examination time of early fetal
      echocardiography. METHODS: The interrogated parameters included total heart
      diameter; heart area and circumference; right and left ventricular diameter;
      diameter, circumference, and area of the thorax; and diameter of the aorta and
      pulmonary trunk. Visualization of the 4-chamber view, 3-vessel view, origin and
      crossover of the great arteries, aortic arch, ductus arteriosus, superior and
      inferior venae cavae, and pulmonary veins was analyzed, and the success rates by
      transvaginal sonography (TVS) and transabdominal sonography (TAS) were
      calculated. RESULTS: Complete evaluation of the fetal heart was impossible at 10
      weeks; the total success rate increased from 45% at 11 weeks to 90% between 12
      and 14 weeks and 100% at 15 weeks. Between 10 and 13 weeks, TVS was superior to
      TAS. At 14 weeks, both methods were similar to each other, and at 15 weeks, TAS
      allowed adequate visualization of all structures. Linear regression analysis
      showed a significant correlation between the interrogated parameters and
      gestational age, crown-rump length, and biparietal diameter (P < .05). The ratio
      of right and left ventricular diameters and the ratio of pulmonary trunk and
      aortic diameters were constant. CONCLUSIONS: Early fetal heart evaluation by TVS
      or TAS or both is reasonable and feasible. Our normative data could be helpful
      for understanding the normal development of the fetal heart and great arteries
      and for detection of cardiac defects in early pregnancy.

PMID- 16439781
TI  - Detection rate of early fetal echocardiography and in utero development of
      congenital heart defects.
AB  - OBJECTIVE: The purpose of this study was to evaluate the detection rate of early
      fetal echocardiography and the in utero development of congenital heart defects
      (CHD). METHODS: Cases were selected from all singleton pregnancies between 1997
      and 2003 in which detailed fetal 2-dimensional and color-coded Doppler
      echocardiography was performed in our prenatal unit between 11 weeks' and 13
      weeks 6 days' gestation; 2165 cases with complete outcome parameters were
      analyzed. RESULTS: During this study period, CHD were diagnosed in 46 fetuses.
      Between 11 and 13 weeks' gestation, 29 CHD were diagnosed (11 weeks, 9 cases; 12
      weeks, 8 cases; and 13 weeks, 12 cases); 9 CHD were found in the second trimester
      and 2 in the third trimester. The in utero detection rate of fetal
      echocardiography was 86.96% (n = 40). Six additional CHD (13.04%) were detected
      postnatally. The spectrum of detected CHD changed with advancing gestational age
      and was different from the postnatal detected heart defects. CONCLUSIONS: Early
      fetal echocardiography is feasible and allows the detection of most CHD.
      Congenital heart defects vary in appearance at different stages of pregnancy and
      may evolve in utero with advancing gestational age. Therefore, early fetal
      echocardiography should always be followed by echocardiography at mid gestation.

PMID- 16439782
TI  - Trends in fetal echocardiography and implications for clinical practice: 1985 to
      2003.
AB  - OBJECTIVE: The purpose of this study was to determine whether patterns of
      referral for fetal echocardiography (FE) and the subsequent yield for structural
      congenital heart disease (CHD) have changed between 1985 and 2003. METHODS: All
      FE performed between 1985 and 2003 at Yale-New Haven Hospital was reviewed. The
      primary indication for study and the presence of structural CHD were recorded,
      and data were analyzed for trends. Linear regression with Pearson coefficient
      calculation and Mantel-Haenszel chi(2) analysis were performed (P < .05
      significant). RESULTS: Between 1985 and 2003, 10,806 patients had FE at Yale-New
      Haven Hospital, and 774 cases of structural CHD were detected. The annual number
      of studies and rate of detected structural CHD remained constant through the
      study period. There was a significant increase in the proportion of studies for
      diabetes, maternal structural CHD, suspicious 4-chamber heart, and family history
      of cardiac disease. There was a significant decrease in the proportion of studies
      for a previous child with structural CHD, cardiac teratogen exposure, other fetal
      anomalies, aneuploidy, fetal arrhythmia, and nonimmune hydrops. The percentage of
      structural CHD detected by indication remained constant through the study period.
      Subgroup analysis of diabetes revealed an increase in class B diabetes, while
      classes C and D remained stable. CONCLUSIONS: This is one of the largest series
      of FE and suggests that the pattern of indications has changed since 1985.
      Specifically, referral for diabetes (mostly class B) has increased without a
      change in yield of structural CHD by indication for sonography. The changing
      referral patterns reflect a change in obstetric demographics and has implications
      for obstetric care.

PMID- 16439783
TI  - Third ventricle midline shift due to spontaneous supratentorial intracerebral
      hemorrhage evaluated by transcranial color-coded sonography.
AB  - OBJECTIVE: We aimed to assess the clinical usefulness of the third ventricle
      midline shift (MLS) evaluated by transcranial color-coded sonography (TCCS) in
      acute spontaneous supratentorial intracerebral hemorrhage (ICH). METHODS:
      Consecutive patients with acute (<24 hours after symptom onset) ICH were
      recruited for this TCCS study. Sonographic measurement of MLS and the pulsatility
      index (PI) of the middle cerebral arteries were compared with head computed
      tomographic (CT) data, including MLS, and hematoma volume. Poor functional
      outcome at 30 days after stroke onset was defined as modified Rankin scale
      greater than 2. RESULTS: There were 51 patients with spontaneous supratentorial
      ICH who received CT and TCCS studies within a 12-hour window. Correlation between
      MLS by TCCS (mean +/- SD, 3.2 +/- 2.6 mm) and CT (3.0 +/- 2.4 mm) was high (gamma
      = 0.91; P < .01). There was also a good linear correlation between hematoma
      volume and MLS by TCCS (gamma = 0.81; P < .01). Compared with ICH volume less
      than 25 mL, those with greater volume had more severe MLS and a higher PI of the
      ipsilateral middle cerebral artery (P < .001). Midline shift by TCCS was more
      sensitive and specific than the PI in detecting large ICH (accuracy = 0.82 if MLS
      > or = 2.5 mm), and it was also a significant predictor of poor outcome (odds
      ratio, 2.09 by 1-mm increase; 95% confidence interval, 1.06-4.13). CONCLUSIONS:
      Midline shift may be measured reliably by TCCS in spontaneous supratentorial ICH.
      Our study also showed that MLS on TCCS is a useful and convenient method to
      identify patients with large ICH and hematoma expansion and to predict short-term
      functional outcome.

PMID- 16439784
TI  - B-flow imaging for assessment of 70% to 99% internal carotid artery stenosis
      based on residual lumen diameter.
AB  - OBJECTIVE: The purpose of this study was to use B-flow imaging (BFI) to
      investigate whether the minimal residual lumen diameter (MRLD) measurement can be
      used in place of the North American Symptomatic Carotid Endarterectomy Trial
      (NASCET) method of measurement. METHODS: One hundred sixty-three consecutive
      patients with internal carotid artery (ICA) stenosis were examined with BFI and
      digital subtraction angiography. The diagnostic performances of the NASCET method
      of measurement with the BFI and MRLD measurements in determining 70% to 99% ICA
      stenosis were compared by performing receiver operating characteristic curve
      analysis. RESULTS: There was no difference between the performances of the two
      methods in estimating 70% to 99% ICA stenosis (area under the receiver operating
      characteristic curve was 0.979 for the NASCET method and 0.978 for the MRLD
      measurement; P = .899). In the assessment of ICA stenosis, an MRLD measurement of
      1.5 mm was determined as the optimal threshold value. The sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of this threshold were 93%, 94%, 84%, 97%, and 94%, respectively. CONCLUSIONS: In
      the BFI examination, when the distal ICA, which is the denominator in the NASCET
      method of measurement, cannot be measured at all or cannot be measured
      accurately, an MRLD measurement that is equal to or less than 1.5 mm is the
      criterion that can be used with confidence in determining 70% to 99% ICA
      stenosis.

PMID- 16439785
TI  - Ultrasonographic assessment of arterial cross-sectional area in the thoracic
      outlet on postural maneuvers measured with power Doppler ultrasonography in both
      asymptomatic and symptomatic populations.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility and
      potential usefulness of power Doppler ultrasonography (PDU) in the assessment of
      changes in arterial cross-sectional area in the thoracic outlet during upper limb
      elevation. METHODS: Forty-four volunteers and 28 patients with a clinical
      diagnosis of arterial thoracic outlet syndrome were evaluated by B-mode imaging
      and PDU. Arterial cross-sectional area was assessed in the 3 compartments of the
      thoracic outlet with the arm alongside the body and at 90 degrees, 130 degrees,
      and 170 degrees of abduction. The percentage of arterial stenosis was calculated
      for each of these arm positions. Nineteen of the 28 patients were also assessed
      by magnetic resonance (MR) imaging. RESULTS: No significant arterial stenosis was
      shown in the interscalene triangle and in the retropectoralis minor space of the
      volunteers and patients. A significant difference (P < .01) in stenosis between
      volunteers and patients was seen for all degrees of abduction in the
      costoclavicular space. The 130 degrees hyperabduction maneuver appeared to be the
      most discriminating postural maneuver. Seven patients assessed with MR imaging
      did not have any arterial stenosis on MR images, whereas an appreciable degree of
      arterial stenosis was shown with ultrasonography. CONCLUSIONS: Arterial
      compression inside the thoracic outlet can be detected and quantified with B-mode
      imaging in association with PDU.

PMID- 16439786
TI  - Diaphragm ultrasonography as an alternative to whole-body plethysmography in
      pulmonary function testing.
AB  - OBJECTIVE: Whole-body plethysmography is a common method of measuring pulmonary
      function. Although this technique provides a sensitive measure of pulmonary
      function, it can be problematic and unsuitable in some patients. The development
      of more accessible techniques would be beneficial. METHODS: A prospective study
      was performed to validate diaphragm ultrasonography as an alternative to whole
      body plethysmography in patients referred for pulmonary function testing.
      Diaphragm movement and position were assessed by ultrasonography after standard
      pulmonary function testing using whole-body plethysmography. RESULTS: A wide
      range of lung function was observed. Standard lung volumes were as follows: total
      lung capacity, 5.57 +/- 1.31 L, residual volume, 2.27 +/- 0.56 L; and vital
      capacity, 3.30 +/- 0.98 L (mean +/- SD). The ratio of forced expiratory volume in
      1 second to forced vital capacity was calculated as 0.69 +/- 0.08.
      Ultrasonography showed that mean diaphragm excursion values were 11.1 +/- 3.8 mm
      (2-dimensional), 14.7 +/- 4.1 mm during quiet breathing (M-mode), and 14.8 +/-
      3.9 mm during a maximal sniff (M-mode). The velocity of diaphragm movement rose
      sharply during the sniff maneuver from 15.2 +/- 5.8 mm/s during quiet breathing
      to 104.0 +/- 33.4 mm/s. Static 2-dimensional measures of diaphragm position at
      the end of quiet inspiration or expiration correlated with standard measures of
      lung volume on plethysmography (eg, a correlation coefficient of 0.83 was
      obtained with end inspiration and vital capacity). All measures of diaphragm
      movement (whether by 2-dimensional or M-mode techniques) were poorly correlated
      with any lung volumes measured. CONCLUSIONS: These data suggest that dynamic
      measurements using diaphragm ultrasonography provide a relatively poor measure of
      pulmonary function in relation to whole-body plethysmography.

PMID- 16439787
TI  - Short- and long-term effects of emergency medicine sonography on formal
      sonography use: a decade of experience.
AB  - OBJECTIVES: It has been reported that use of formal sonographic studies by
      departments of radiology initially increases after inception of an emergency
      medicine (EM) sonography training program, but there are no data on whether this
      trend continues as the training program matures. The purpose of this study was to
      evaluate the effect of an ongoing EM sonography program on formal sonography use
      after more than a decade of experience. METHODS: This retrospective, computer
      assisted review compared emergency department (ED) abdominal sonographic studies
      ordered in the 3 years before inception of an EM sonography program (1992-1994)
      with those ordered in the 8 years after its inception (1995-2002). To determine
      the relative change, all abdominal sonograms ordered by ED physicians were
      compared with equivalent outpatient formal sonograms by all other physicians in
      the hospital. The study site is a community teaching hospital with a current ED
      census of 50,000. RESULTS: In the initial 4 years (1995-1998), the number of
      formal studies increased significantly in both absolute numbers (annual mean, 95
      versus 162; P < .002) and as a percentage of all outpatient sonograms ordered at
      the institution (5.1% versus 8.5%; P < .0001). However, in the following 4 years
      (1999-2002), the absolute number of formal studies remained constant but
      decreased when adjusted for an increased ED census. Emergency department-ordered
      formal studies also decreased as a percentage of all sonograms ordered (5.1%
      versus 4.1%; P = .002). CONCLUSIONS: Emergency department use of formal
      sonography services increases with the introduction of ED sonography but
      decreases markedly as the program matures.

PMID- 16439788
TI  - The premaxillary triangle: clue to the diagnosis of cleft lip and palate.
AB  - OBJECTIVE: The prenatal detection rate of cleft lip and palate is low, especially
      in low-risk patients who undergo targeted sonography. The reason is that
      evaluating surface anatomy is relatively difficult and requires operator
      expertise. Our purpose was to describe a technique to improve the diagnostic
      accuracy of facial clefts (lip and palate) and to assess the feasibility of
      including this technique as part of standard protocol during targeted imaging.
      METHODS: A prospective study was done during 2000 through 2002 to evaluate the
      accuracy of the "premaxillary triangle (PMT) sign": a new sign to diagnose
      unilateral cleft lip and palate in women referred for prenatal sonography at our
      center. Patients with only isolated unilateral cleft lip and palate and cleft lip
      were included in this study. Before this, all examiners were trained to image the
      PMT. The images were reviewed by a senior consultant. It was later decided to
      include this sign as part of the protocol of targeted sonography done between 18
      and 22 weeks in our institution. However, depending on the fetal position, the
      PMT was documented even in patients referred for the first time in late second
      and third trimesters. RESULTS: Twenty-nine cases of isolated facial clefts were
      diagnosed during the study period, of which 2 had unilateral cleft lip and 27 had
      unilateral cleft lip and palate. The PMT sign was absent in all cases of
      unilateral cleft lip and palate but was present in 2 cases of isolated cleft lip
      without cleft palate. CONCLUSIONS: The PMT sign can be easily incorporated into
      targeted sonography at 18 to 22 weeks' gestation. Its inclusion would help in
      increasing the detection rate of unilateral cleft lip and palate. It may also be
      potentially used for differentiating between isolated cleft lip and cleft lip and
      palate, which helps in better prenatal counseling.

PMID- 16439789
TI  - Prenatal diagnosis of ventriculocoronary arterial communication in fetuses with
      hypoplastic left heart syndrome.
AB  - OBJECTIVE: The purpose of this series was to describe the fetal echocardiographic
      findings in hypoplastic left heart syndrome with aortic atresia and
      ventriculocoronary arterial communication and implications of these findings.
      METHODS: We describe 2 fetuses with hypoplastic left heart syndrome with
      ventriculocoronary arterial communication diagnosed at 29 and 20 weeks'
      gestation, respectively. The underlying cardiac anatomy consisted of a
      hypoplastic left heart and mitral stenosis with aortic atresia. We used color
      Doppler and pulsed Doppler sonography on the surface of the myocardium to
      specifically look for coronary arterial flow. RESULTS: By color Doppler
      sonography, ventriculocoronary arterial communication was shown between the left
      ventricular cavity and the left coronary artery with characteristic bidirectional
      flow on pulsed Doppler examination. There was no mitral regurgitation. The left
      ventricular myocardium was substantially hypertrophied. The first patient
      underwent surgical Norwood palliation and died after a prolonged postoperative
      course. The second patient underwent stenting of the arterial duct and bilateral
      pulmonary artery banding in the catheterization laboratory but died after a few
      weeks. Implications of ventriculocoronary arterial communication in association
      with hypoplastic left heart syndrome are discussed. CONCLUSIONS: It is possible
      to accurately diagnose ventriculocoronary arterial communication on fetal
      echocardiography. The presence of ventriculocoronary arterial communication is
      seen exclusively in a subgroup of patients with an aortic atresia and mitral
      stenosis variant of hypoplastic left heart syndrome. The prognosis is poor in
      this subgroup of patients.

PMID- 16439790
TI  - Fetal echocardiographic diagnosis of vascular rings.
AB  - OBJECTIVE: The purpose of this series is to describe the prenatal
      echocardiographic findings of vascular rings. METHODS: The 3-vessel and trachea
      view consists of the axial view of the upper mediastinum. The normal left aortic
      arch appears as a V-shaped confluence of the ductus arteriosus and aortic arch,
      with the trachea situated posterior and to the right. No vessel should encircle
      the trachea. The diagnoses of vascular rings were made prenatally and were
      confirmed in all patients postnatally. RESULTS: Six fetuses had diagnoses of
      vascular rings. The mean gestational age at diagnosis was 23.3 weeks (range, 18
      31 weeks). The indications for fetal echocardiography were family history of
      congenital heart disease, echogenic focus in the left ventricle, and abnormal 4
      chamber view. There were 2 fetuses with a double aortic arch; 3 fetuses with a
      right aortic arch, an aberrant left subclavian artery, and a left ductus
      arteriosus; and 1 with a right circumflex aortic arch with a left ductus
      arteriosus and an aberrant left subclavian artery. Two fetuses had associated
      structural cardiac defects, 1 with an unbalanced atrioventricular septal defect
      and trisomy 21 and the other with a double-outlet right ventricle, pulmonary
      atresia, and multiple other congenital anomalies. CONCLUSIONS: Vascular rings can
      be accurately diagnosed prenatally with recognition of a vascular structure that
      courses around the trachea and absence of the usual V-shaped relationship of the
      aortic and ductal arches. The color Doppler findings and the presence of a ductus
      arteriosus aid in identifying various components of the vascular ring.

PMID- 16439791
TI  - Fetus in fetu and fetaform teratoma in 2 neonates: an embryologic spectrum?
AB  - OBJECTIVE: The purpose of this study was to describe the imaging and pathologic
      findings of 2 cases of complex neonatal abdominal masses and to discuss the
      probable common embryologic etiology of fetus in fetu (FIF) and fetaform
      teratomas. METHODS: Two male neonates had complex cystic abdominal masses, 1 of
      which was diagnosed prenatally, and both had abdominal sonography. One patient
      also had abdominal computed tomography. Both patients subsequently underwent
      surgical resection, with pathologic and genetic analysis of these masses.
      RESULTS: One patient had typical imaging, pathologic, and genetic findings of
      FIF. The second patient had a well-formed mass that was diagnosed pathologically
      as a teratoma yet had most of the criteria for FIF that have been set forth in
      recent embryologic literature. CONCLUSIONS: Recent concepts regarding the origin
      of FIF suggest that it is part of a spectrum of monozygotic twinning gone awry,
      ranging from conjoined twins at one end to fetaform teratomas at the other. The
      imaging and pathologic features of these 2 cases serve to reinforce this concept.

PMID- 16439792
TI  - Transvaginal sonographic diagnosis of a large retroperitoneal pelvic epidermoid
      cyst (monodermal teratoma).

PMID- 16439793
TI  - Transvaginal sonography of hematotrachelos and hematometra causing acute urinary
      retention after previous repair of intrapartum cervical lacerations.

PMID- 16439794
TI  - The chinese ring: a contraceptive intrauterine device.

PMID- 16439796
TI  - Sonographic appearance of nodular fasciitis.

PMID- 16439795
TI  - Extraintestinal Salmonella infection appearing as a suspicious breast mass.

PMID- 16439797
TI  - Sign of subendocardial ischemia on echocardiography.

PMID- 16439798
TI  - Sonographic findings in dissection of extracranial brain-supplying arteries.

PMID- 16439799
TI  - AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to
      activate Erk1/2.
AB  - Bacterial flagellin can interact with both Toll-like receptor 5 (TLR5) and the
      cell surface glycolipid, asialoGM1, to activate an innate immune response. The
      induction of mucin by flagellin in human lung epithelial cells (NCIH292) is
      dependent on asialoGM1 ligation, ATP receptor signaling, Ca2+ mobilization, and
      Erk1/2 activation. Conversely, the activation of NF-kappaB by flagellin is
      dependent on signaling through TLR5. These results prompted us to ask whether the
      flagellin-induced TLR5 signaling pathway was intersecting with or mutually
      independent of the nucleotide receptor pathway activated downstream of asialoGM1.
      Herein, we demonstrate that the release of ATP induced by flagellin is dependent
      on a Toll signaling cascade. Although Toll was able to activate NF-kappaB in the
      absence of extracellular ATP, Toll required ATP to activate Erk1/2. These results
      suggest interdependence between the asialoGM1 and TLR5 pathways and reveal a
      previously unsuspected role for autocrine extracellular ATP signaling in TLR
      signaling.

PMID- 16439800
TI  - Effect of cholesterol depletion on exocytosis of alveolar type II cells.
AB  - Alveolar epithelial type II cells secrete lung surfactant via exocytosis. Soluble
      N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) are
      implicated in this process. Lipid rafts, the cholesterol- and sphingolipid-rich
      microdomains, may offer a platform for protein organization on the cell membrane.
      We tested the hypothesis that lipid rafts organize exocytotic proteins in type II
      cells and are essential for the fusion of lamellar bodies, the secretory granules
      of type II cells, with the plasma membrane. The lipid rafts, isolated from type
      II cells using 1% Triton X-100 and a sucrose gradient centrifugation, contained
      the lipid raft markers, flotillin-1 and -2, whereas they excluded the nonraft
      marker, Na+-K+ ATPase. SNAP-23, syntaxin 2, and VAMP-2 were enriched in lipid
      rafts. When type II cells were depleted of cholesterol, the association of SNAREs
      with the lipid rafts was disrupted and the formation of fusion pore was
      inhibited. Furthermore, the cholesterol-depleted plasma membrane had less ability
      to fuse with lamellar bodies, a process mediated by annexin A2. The secretagogue
      stimulated secretion of lung surfactant from type II cells was also reduced by
      methyl-beta-cyclodextrin. When the raft-associated cell surface protein, CD44,
      was cross-linked using anti-CD44 antibodies, the CD44 clusters were observed.
      Syntaxin 2, SNAP-23, and annexin A2 co-localized with the CD44 clusters, which
      were cholesterol dependent. Our results suggested that lipid rafts may form a
      functional platform for surfactant secretion in alveolar type II cells, and raft
      integrity was essential for the fusion between lamellar bodies with the plasma
      membrane.

PMID- 16439802
TI  - Fibroblast growth factor 2 and transforming growth factor beta1 synergism in
      human bronchial smooth muscle cell proliferation.
AB  - Bronchial smooth muscle cell (BSMC) hyperplasia is a typical feature of airway
      remodeling and contributes to airway obstruction and hyperresponsiveness in
      asthma. Fibroblast growth factor 2 (FGF-2) and transforming growth factor beta1
      (TGF-beta1) are sequentially upregulated in asthmatic airways after allergic
      challenge. Whereas FGF-2 induces BSMC proliferation, the mitogenic effect of TGF
      beta1 remains controversial, and the effect of sequential FGF-2 and TGF-beta1 co
      stimulation on BSMC proliferation is unknown. This study aimed to assess the
      individual and sequential cooperative effects of FGF-2 and TGF-beta1 on human
      BSMC proliferation and define the underlying mechanisms. Mitogenic response was
      measured using crystal violet staining and [3H]-thymidine incorporation. Steady
      state mRNA and protein levels were measured by semiquantitative RT-PCR, Western
      blot, and ELISA, respectively. TGF-beta1 (0.1-20 ng/ml) alone had no effect on
      BSMC proliferation, but increased the proliferative effect of FGF-2 (2 ng/ml) in
      a concentration-dependent manner (up to 6-fold). Two distinct platelet-derived
      growth factor receptor (PDGFR) inhibitors, AG1296 and Inhibitor III, as well as a
      neutralizing Ab against PDGFRalpha, partially blocked the synergism between these
      two growth factors. In this regard, TGF-beta1 increased PDGF-A and PDGF-C mRNA
      expression as well as PDGF-AA protein expression. Moreover, FGF-2 pretreatment
      increased the mRNA and protein expression of PDGFRalpha and the proliferative
      effect of exogenous PDGF-AA (140%). Our data suggest that FGF-2 and TGF-beta1
      synergize in BSMC proliferation and that this synergism is partially mediated by
      a PDGF loop, where FGF-2 and TGF-beta1 upregulate the receptor (PDGFRalpha) and
      the ligands (PDGF-AA and PDGF-CC), respectively. This powerful synergistic effect
      may thus contribute to the hyperplastic phenotype of BSMC in remodeled asthmatic
      airways.

PMID- 16439801
TI  - Airborne particulate matter inhibits alveolar fluid reabsorption in mice via
      oxidant generation.
AB  - Ambient particulate matter is increasingly recognized as a significant
      contributor to human cardiopulmonary morbidity and mortality in the United States
      and worldwide. We sought to determine whether exposure to ambient particulate
      matter would alter alveolar fluid clearance in mice. Mice were exposed to a range
      of doses of a well-characterized particulate matter collected from the ambient
      air in Dusseldorf, Germany through a single intratracheal instillation, and
      alveolar fluid clearance and measurements of lung injury were made. Exposure to
      even very low doses of particulate matter (10 microg) resulted in a significant
      reduction in alveolar fluid clearance that was maximal 24 h after the exposure,
      with complete resolution after 7 d. This was paralleled by a decrease in lung
      Na,K-ATPase activity. To investigate the mechanism of this effect, we measured
      plasma membrane Na,K-ATPase abundance in A549 cells and Na,K-ATPase activity in
      primary rat alveolar type II cells after exposure to particulate matter in the
      presence or absence of the combined superoxide dismutase and catalase mimetic EUK
      134 (5 microM). Membrane but not total protein abundance of the Na,K-ATPase was
      decreased after exposure to particulate matter, as was Na,K-ATPase activity. This
      decrease was prevented by the combined superoxide dismutase/catalase mimetic EUK
      134. The intratracheal instillation of particulate matter results in alveolar
      epithelial injury and decreased alveolar fluid clearance, conceivably due to
      downregulation of the Na,K-ATPase.

PMID- 16439803
TI  - Flagellar activation of epithelial signaling.
AB  - Mucosal epithelial cells are an important component of the innate immune system
      forming a physical and immunologic barrier to inhaled bacteria. As polarized
      cells with tight junctions, the immunologic signaling functions of airway
      epithelial cells differ from those of professional immune cells. While many
      bacterial gene products activate airway mucosal cells, flagella are especially
      immunostimulatory. The motility function provided by flagella is essential for
      the initial stages of respiratory infection associated with opportunists such as
      Pseudomonas aeruginosa. Apically presented toll-like receptor 5 responds
      specifically to bacterial flagellin transducing a number of epithelial
      proinflammatory signaling cascades, including the induction of Ca2+ fluxes;
      activation of NF-kappaB, IL-8, and matrilysin; and mucin expression. The
      complexities of flagella and flagellin structures, how these bacterial components
      initiate host signaling and their potential as a vaccine target are reviewed.

PMID- 16439805
TI  - Early emphysema in the tight skin and pallid mice: roles of microfibril
      associated glycoproteins, collagen, and mechanical forces.
AB  - The nature of the development of emphysema in the tight skin (Tsk) and the pallid
      (Pa) mice are not well understood. We assessed the mechanical and nonlinear
      properties of the respiratory system, the alveolar structure, and the levels of
      microfibril-associated glycoproteins (MAGP) 1 and 2 in Tsk mice with
      developmental emphysema; in Pa mice, which are thought to develop adult onset
      emphysema; and their background, the C57BL/6 mice, at an age of 7 wk. Minor
      differences between collagen-related elastic properties of the lungs of the Pa
      and C57BL/6 mice were seen at this early age. The lungs of the Tsk mice were
      significantly softer yet more nonlinear than those of the Pa and C57BL/6 mice.
      The MAGP-1 levels were similar in all three groups. However, the level of MAGP-2,
      which is associated with both fibrillin-1 and collagen, was higher in the Tsk
      than in the Pa mice, which also had more MAGP-2 than the C57BL/6. Both the mean
      and the variance of alveolar diameters were larger in the Tsk than in the other
      two groups, while the variance in the Pa was larger than in the C57BL/6 mice,
      implying early development of heterogeneity. Using a network model of the
      parenchyma, we linked the pathophysiologic changes in the Tsk mice to mechanical
      forces and failure of the alveolar walls. Our findings suggest the possibility
      that MAGP-2-related abnormal collagen assembly, combined with mechanical forces,
      is involved in the progression of emphysema in the Tsk mice.

PMID- 16439806
TI  - BAC to the future! or oligonucleotides: a perspective for micro array comparative
      genomic hybridization (array CGH).
AB  - The array CGH technique (Array Comparative Genome Hybridization) has been
      developed to detect chromosomal copy number changes on a genome-wide and/or high
      resolution scale. It is used in human genetics and oncology, with great promise
      for clinical application. Until recently primarily PCR amplified bacterial
      artificial chromosomes (BACs) or cDNAs have been spotted as elements on the
      array. The large-scale DNA isolations or PCR amplifications of the large-insert
      clones necessary for manufacturing the arrays are elaborate and time-consuming.
      Lack of a high-resolution highly sensitive (commercial) alternative has
      undoubtedly hindered the implementation of array CGH in research and diagnostics.
      Recently, synthetic oligonucleotides as arrayed elements have been introduced as
      an alternative substrate for array CGH, both by academic institutions as well as
      by commercial providers. Oligonucleotide libraries or ready-made arrays can be
      bought off-the-shelf saving considerable time and efforts. For RNA expression
      profiling, we have seen a gradual transition from in-house printed cDNA-based
      expression arrays to oligonucleotide arrays and we expect a similar transition
      for array CGH. This review compares the different platforms and will attempt to
      shine a light on the 'BAC to the future' of the array CGH technique.

PMID- 16439804
TI  - Roles of apoptosis in airway epithelia.
AB  - The airway epithelium functions primarily as a barrier to foreign particles and
      as a modulator of inflammation. Apoptosis is induced in airway epithelial cells
      (AECs) by viral and bacterial infections, destruction of the cytoskeleton, or by
      exposure to toxins such as high oxygen and polycyclic hydrocarbons. Various
      growth factors and cytokines including TGF-beta, IFN-gamma, or the activators of
      the death receptors, TNF-alpha and FasL, also induce apoptosis in AECs. However,
      cell death is observed in maximally 15% of AECs after 24 h of treatment.
      Preincubation with IFN-gamma or a zinc deficiency increases the percentage of
      apoptotic AECs in response to TNF-alpha or FasL, suggesting that AECs have
      mechanisms to protect them from cell death. Apoptosis of AECs is a major
      mechanism in reducing cell numbers after hyperplastic changes in airway epithelia
      that may arise due to major injuries in response to LPS or allergen exposures.
      Resolution of hyperplastic changes or changes during prolonged exposure to an
      allergen is primarily regulated by the Bcl-2 family of proteins. Fas and FasL are
      both expressed in AECs, and their main function may be to control inflammation by
      inducing Fas-induced death in inflammatory cells without inducing apoptosis in
      neighboring cells. Furthermore, AECs engulf dying eosinophils to clear them by
      phagocytosis. Therefore, in the airway epithelium apoptosis serves three main
      roles: (1) to eliminate damaged cells; (2) to restore homeostasis following
      hyperplastic changes; and (3) to control inflammation, and thereby support the
      barrier and anti-inflammatory functions.

PMID- 16439807
TI  - Structures and biological activities of novel phosphatidylethanolamine lipids of
      Porphyromonas gingivalis.
AB  - The Gram-negative periodontal pathogen Porphyromonas gingivalis synthesizes
      several classes of novel phosphorylated complex lipids, including the recently
      characterized phosphorylated dihydroceramides. These sphingolipids promote the
      interleukin-1 (IL-1)-mediated secretion of inflammatory mediators from
      fibroblasts, including prostaglandin E2 and 6-keto prostaglandin F2alpha, and
      alter gingival fibroblast morphology in culture. This report demonstrates that
      one additional class of phosphorylated complex lipids of P. gingivalis promotes
      IL-1-mediated secretory responses and morphological changes in cultured
      fibroblasts. Structural characterization identified the new phospholipid class as
      1,2-diacyl phosphatidylethanolamine, which substituted predominantly with
      isobranched C15:0 and C13:0 fatty acids. The isobranched fatty acids, rather than
      unbranched fatty acids, and the phosphoethanolamine head group were identified as
      the essential structural elements required for the promotion of IL-1-mediated
      secretory responses. These structural components are also observed in specific
      phosphorylated sphingolipids of P. gingivalis and likely contribute to the
      biological activity of these substances, in addition to the
      phosphatidylethanolamine lipids described in this report.

PMID- 16439808
TI  - Lipids isolated from bone induce the migration of human breast cancer cells.
AB  - Bone is the most common site to which breast cancer cells metastasize. We found
      that osteoblast-like MG63 cells and human bone tissue contain the bile acid salt
      sodium deoxycholate (DC). MG63 cells take up and accumulate DC from the medium,
      suggesting that the bone-derived DC originates from serum. DC released from MG63
      cells or bone tissue promotes cell survival and induces the migration of
      metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor farnesoid
      X receptor (FXR) antagonist Z-guggulsterone prevents the migration of these cells
      and induces apoptosis. DC increases the gene expression of FXR and induces its
      translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is
      concurrent with the increase of urokinase-type plasminogen activator (uPA) and
      the formation of F-actin, two factors critical for the migration of breast cancer
      cells. Our results suggest a novel mechanism by which DC-induced increase of uPA
      and binding to the uPA receptor of the same breast cancer cell self-propel its
      migration and metastasis to the bone.

PMID- 16439810
TI  - The anal bag: a modern approach to fecal incontinence management.
AB  - In the past 30 years, colostomy and urostomy bags have dramatically improved the
      quality of life of ostomy patients. However, the anatomical characteristics and
      physiological motility of the pelvic floor have hampered the development of
      suitable disposable containers that can be applied directly to the anus. Use of a
      recently developed anal bag that insulates the anus and peri-anal area and
      collects stool was evaluated in two inpatient care settings in Italy from 1994 to
      2004. The study included four nurses and eight physicians (four
      gastroenterologists, two cardiologists, and two gerontologists) involved in the
      care of 120 patients (65 men, 55 women, ages 45 to 96 years). The study
      population consisted of patients who were elderly and bedridden (47), had
      pressure ulcers (15), were affected by fecal incontinence or bedridden in
      intensive care (10), had coronary problems (10), and were receiving high-dose
      chemotherapy (10); patients who had undergone anorectal surgery (28) were added
      to the study to evaluate the anal bag for postoperative use to prevent
      contamination and contain exudate and fluid. Study participants were divided into
      groups based on length of anal bag use (3 days, 1 week, or 4 months or more).
      Objective evaluation at each bag change included skin reactions to the adhesive.
      Study participants feelings and perceptions as well as nurse and physician
      evaluations of the anal bag were assessed using questionnaires and four-point
      rating scales. No adverse reactions to the product were observed and none of the
      high-risk patients developed a pressure ulcer. The majority of patients (91, 76%)
      tolerated the bag well and reported it was not painful to remove or apply (102,
      85%). Nurses and physicians all considered the device easy to use and appreciated
      its potential to prevent contamination and cross-contamination. This device may
      help improve the management of fecal incontinence and prevent complications.

PMID- 16439812
TI  - Alleviating debilitating, chronic constipation with colostomy after
      appendicostomy: a case study.
AB  - Severe chronic constipation is a debilitating condition. Patients not only
      experience infrequent bowel movements, but also are often frustrated by the
      sensation of incomplete evacuation; pain; straining; daily use of enemas; and
      continual concerns regarding diet, fluids, and medications. Diagnostic tests are
      performed to rule out organic causes of the condition. Common treatment options
      consist of dietary fiber supplementation, dietary instruction, adequate fluid
      intake, enemas, and laxatives; additional noninvasive management includes
      biofeedback training and botulinum toxin type A injections. Surgery is rarely
      recommended, although a select group of patients may benefit from antegrade
      continence enema procedure. A female patient presented with a history of long
      standing constipation. When antegrade continence enema offered no improvement and
      other treatment measures failed, she underwent successful laparoscopic-assisted
      sigmoid resection and end colostomy. This approach may provide options for
      patients in similar circumstances.

PMID- 16439809
TI  - A controlled, three-part trial to investigate the barrier function and skin
      hydration properties of six skin protectants.
AB  - In the treatment of incontinence dermatitis, a skin protectant primarily prevents
      skin breakdown due to moisture and biological irritants in urine and feces. To
      assess the barrier and skin hydration properties of six currently available skin
      protectants with different formulations, a controlled, three-phase study was
      conducted at a research facility in the UK among 18 healthy volunteers. The study
      addressed each product's efficacy against insult from a known irritant (sodium
      lauryl sulphate), skin hydration potential, and maintenance of skin barrier and
      barrier efficacy against maceration. Using white petrolatum (glycerin) as the
      positive control and untreated sites as the negative control, the results show
      that each one of the products tested has different performance properties.
      Products containing petrolatum demonstrated protection against irritants (P =
      0.006 at 24 hours) and maceration (P < 0.005) and provided some skin hydration.
      Products containing dimethicone varied in protection against irritants (P <
      0.005, or P > or = 0.806 at 24 hours) and have good skin hydration potential and
      low barrier efficacy (P > 0.500). Zinc oxide-based products showed protection
      against irritants (P < 0.005) but poor skin hydration and barrier properties to
      prevent maceration (P = 0.262). Overall, only the water-in-oil petrolatum- based
      product performed effectively within all the parameters tested. This study
      suggests that skin barrier protection involves more than the inclusion of an
      active barrier ingredient. Further testing and use of barrier products in the
      clinical setting will provide additional evidence for appropriate product
      selection.

PMID- 16439811
TI  - Assessment of diaper-clogging potential of petrolatum moisture barriers.
AB  - Petrolatum-based ointments often are used to treat and prevent incontinence
      dermatitis. However, anecdotal reports indicate that petrolatum ointments may
      affect the absorbency of disposable briefs also commonly used in incontinence
      management. To examine whether petrolatum ointments clog a commonly used
      absorbent brief, a randomized, balanced-block design study was conducted in a
      controlled laboratory setting to compare the brief-clogging potential of three
      petrolatum ointments to a non-alcohol barrier film. Test products were applied to
      6-cm x 6-cm test sites on the volar forearms of 16 volunteers. Pre-weighed mini
      briefs were applied to the test sites in a manner that simulates normal brief
      wear. After 5 minutes of wear, the mini briefs were weighed to determine percent
      of product transfer from skin to mini brief. The mini briefs then were reapplied
      to the same test sites and a synthetic urine solution was introduced between the
      skin and the mini brief. Mini briefs subsequently were removed to determine fluid
      uptake by weight. Results indicate significant differences between the four test
      products (P < 0.01) both in percent transfer and in mini brief fluid absorption.
      From 59% to 69% of the petrolatum-based products transferred from the skin to the
      mini briefs and a 54% to 90% reduction in fluid uptake was noted, as determined
      by weight. The non-alcohol barrier film did not transfer to the mini brief and
      fluid uptake was minimally affected. Further study in the clinical and practice
      settings to determine the effect and consequences of barrier product transfer on
      absorbent garments is warranted.

PMID- 16439813
TI  - Self-esteem disturbance in patients with urinary diversions: assessing the void.
AB  - Self-esteem can be affected by any change in health, appearance, or emotional
      status--change that can affect quality of life. A decrease in self-esteem is
      especially evident in people with urinary diversions. A review of the literature,
      conducted to demonstrate self-esteem problems related to this population,
      revealed that body image and sexuality changes related to urinary diversions are
      frequently discussed in the current literature but studies that focus directly on
      self-esteem in the urinary diversion population have not been published. However,
      self-esteem may be compromised in people with urinary diversions more frequently
      than the literature reflects. Patients with urinary diversions, whether continent
      or incontinent, may be at risk for self-esteem problems. Future research and
      exploration are needed to expand knowledge of self-esteem with regard to urinary
      diversions in order to further understand the issue.

PMID- 16439814
TI  - Understanding muscle architectural adaptation: macro- and micro-level research.
AB  - Recent research using muscle-imaging techniques has revealed a remarkable
      plasticity of human muscle architecture where significant changes in fascicle
      lengths and angles have resulted from the chronic performance, or cessation, of
      strong muscle contractions. However, there is a paucity of data describing
      architectural adaptations to chronic stretching, disuse and immobilization,
      illness, and aging, and those data that are available are equivocal.
      Understanding their impact is important in order that effective interventions for
      illness/injury management and rehabilitation, and programs to improve the
      physical capacity of workers, the aged and athletes can be determined.
      Nonetheless, recent advances in myocellular research could provide a framework
      allowing the prediction of architectural changes in these understudied areas.
      Examination of the site-specific response to mechanical stress of calpain
      dependent ubiquitin-proteasome proteolysis, or of the cellular response to stress
      after the knockout (or incapacitation) of sarcomeric and cytoskeletal proteins
      involved in cellular signal transduction, provides an exciting paradigm by which
      myocellular adaptation can be described. Such research might contribute to the
      understanding of macro-level changes in muscle architecture.

PMID- 16439815
TI  - Long-term culture of human urothelial cells--a qualitative analysis.
AB  - Today, in vitro culturing of autologous cells is an established method in the
      field of tissue reconstruction. It can be applied to urothelial cells and could
      have many clinical implications in urological reconstructive surgery. This
      development calls for quality controls concerning cells used for clinical
      treatment when cells are autotransplanted back to the patient. We have studied
      cultured cells in order to detect whether genetic or morphologic changes occur.
      Urothelial cells isolated from bladder lavage were cultured according to
      different protocols based on the presence or absence of feeder cells. Genetic
      studies were performed by means of karyotyping with standard G-banding and
      interphase fluorescent in situ hybridization (FISH) analyses. The morphology of
      these epithelial cells was judged as well as immunostaining for epithelial cell
      markers. In addition, to minimize the risk of feeder cell contamination,
      proliferation studies were performed on cultures including feeder cells that had
      been pretreated with different doses of mitomycin or radiation. In initial
      studies, when using feeder cells in each passage according to standard protocols,
      urothelial cells proliferated unfavourably after the fourth passage with
      increasing numbers of mouse cells as well as urothelial tetraploid cells. We
      could also show that urothelial cells from bladder lavage need feeder cells in
      order to establish primary cultures. Further propagation up to 14 passages was
      performed without feeder cells and the urothelial cells retained normal
      karyotypes. We also found that mitomycin treatment had its main effect on feeder
      cells during the first 2 h. When feeder cells were irradiated, 20 Gy was
      effective and no feeder cell contamination was seen. In conclusion, we found that
      a high standard of quality in urothelial cell culturing can be achieved with a
      careful culturing technique.

PMID- 16439816
TI  - Osteocyte lacuna population densities in sheep, elk and horse calcanei.
AB  - Osteocytes, the most prevalent cell type in bone, appear to communicate via gap
      junctions. In limb-bone diaphyses, it has been hypothesized that these cellular
      networks have the capacity to monitor habitual strains, which can differ
      significantly between cortical locations of the same bone. Regional differences
      in microdamage associated with prevalent/predominant strain mode (tension,
      compression, or shear) and/or magnitude may represent an important "variable"
      detected by this network. This hypothesis was indirectly addressed by examining
      bones subjected to habitual bending for correlations of osteocyte lacuna
      population densities (n/mm(2) bone area, Ot.Lc.N/B.Ar) with locations
      experiencing high and low strain, and/or prevalent/predominant tension,
      compression, and shear. We examined dorsal ("compression"), plantar ("tension"),
      and medial/lateral ("shear" or neutral axis) cortices of mid-diaphyseal sections
      of calcanei of adult sheep, elk, and horses. Ot.Lc.N/B.Ar data, quantified in
      backscattered electron images, were also evaluated in a context of various
      additional structural and material variables (e.g. % ash, cortical thickness,
      porosity, and secondary osteon population). Results showed significant
      differences in dorsal versus plantar comparisons with the highest Ot.Lc.N/B.Ar in
      dorsal cortices of sheep and elk (p < 0.0001); but this was a statistical trend
      in the equine calcanei (p = 0.14). There were no consistent transcortical
      (pericortical to endocortical) differences, and Ot.Lc.N/B.Ar in neutral axes was
      not consistently different from dorsal/plantar cortices. Correlations of
      Ot.Lc.N/B.Ar with structural and material parameters were also poor and/or
      inconsistent within or between species. These results provide little or no
      evidence that the number of osteocyte lacunae has a functional role in
      mechanotransduction pathways that are typically considered in bone adaptation.
      Although dorsal/plantar differences may be adaptations for prevalent/predominant
      strain modes and/or associated microdamage, it is also plausible that they are
      strongly influenced by differences in the bone formation rates that produced the
      tissue in these locations.

PMID- 16439817
TI  - Intermuscular interaction between synergists in rat originates from both
      intermuscular and extramuscular myofascial force transmission.
AB  - The purpose of the present study is to investigate the origin of mechanical
      interactions between the rat extensor digitorum longus (EDL) muscle and the
      grouped tibialis anterior and extensor hallucis longus muscles (TA+EHL). The
      proximal and distal tendons of EDL as well as the tied distal tendons of TA+EHL
      were transected and connected to force transducers. Connective tissues at the
      muscle bellies of the anterior crural compartment were left intact. Supramaximal
      stimulation of the common peroneal nerve activated all muscles maximally and
      simultaneously. Length-isometric force characteristics of distal TA+EHL were
      assessed. Simultaneously, forces exerted at the proximal and distal tendons of
      EDL, kept at constant muscle-tendon complex length and position, were measured.
      Intermuscular interaction was tested in two conditions: (a) after full
      longitudinal compartmental fasciotomy, and (b) after blunt dissection of the
      intermuscular connective tissue linkages between EDL and TA+EHL. Note that in the
      latter condition, intermuscular myofascial pathways were eliminated. In the
      initial condition, lengthening TA+EHL by 12 mm increased proximal (by 0.14 N,
      i.e. 9.5%) and decreased distal EDL force (by 0.21 N, i.e. 11.8%), despite the
      fact that EDL muscle-tendon complex length was kept constant. Blunt dissection
      decreased TA+EHL and distal EDL forces at low TA+EHL lengths only, while proximal
      EDL force decreased for all TA+EHL lengths tested. The dissection caused no
      changes in the TA+EHL length effects on proximal EDL force. In contrast, the
      amplitude of change in the distal EDL force curve decreased significantly (by
      39%) subsequent to blunt dissection. It is concluded that mechanical interaction
      between synergists originates from both intermuscular as well as extramuscular
      connective tissues. The highest contribution, however, should be ascribed to the
      extramuscular pathway.

PMID- 16439818
TI  - Neuromuscular organization of the superior longitudinalis muscle in the human
      tongue. 1. Motor endplate morphology and muscle fiber architecture.
AB  - Proper tongue function is essential for respiration and mastication, yet we lack
      basic information on the anatomical organization underlying human tongue
      movement. Here we use microdissection, acetylcholinesterase histochemistry,
      silver staining of nerves, alpha bungarotoxin binding and immunohistochemistry to
      describe muscle fiber architecture and motor endplate (MEP) distribution of the
      human superior longitudinalis muscle (SL). The human SL extends from tongue base
      to tongue tip and is composed of fiber bundles that range from 2.8 to 15.7 mm in
      length. Individual muscle fibers of the SL range from 1.2 to 17.3 mm in length
      (1.3-18.2% of muscle length). Seventy-one percent of SL fibers have blunt-blunt
      terminations; the remainder have blunt-taper terminations. Multiple MEPs are
      present along SL length and dual MEPs are present on some muscle fibers. These
      data demonstrate that the human SL is a muscle of "in-series" design. We suggest
      that SL motor units are organized to innervate specific regions of the tongue
      body and that activation of SL motor units according to anteroposterior location
      is one strategy employed by the nervous system to control tongue shape and tongue
      movement.

PMID- 16439819
TI  - Force platform measurements as predictors of falls among older people - a review.
AB  - BACKGROUND: Poor postural balance is one of the major risk factors for falling. A
      great number of reports have analyzed the risk factors and predictors of falls
      but the results have for the most part been unclear and partly contradictory.
      Objective data on these matters are thus urgently needed. The force platform
      technique has widely been used as a tool to assess balance. However, the ability
      of force platform measures to predict falls remains unknown. OBJECTIVE: The
      purpose of this systematic review was to extract and critically review the
      findings of prospective studies where force platform measurements have been used
      as predictors of falls among elderly populations. METHODS: The study was done as
      a systematic literature review. PubMed, the Cochrane Central Register of
      Controlled Trials, and CINAHL databases from 1950 to April 2005 were used. The
      review includes prospective follow-up studies using the force platform as a tool
      to measure postural balance. RESULTS: Nine original prospective studies were
      included in the final analyses. In five studies fall-related outcomes were
      associated with some force platform measures and in the remaining four studies
      associations were not found. For the various parameters derived on the basis of
      the force platform data, the mean speed of the mediolateral (ML) movement of the
      center of pressure (COP) during normal standing with the eyes open and closed,
      the mean amplitude of the ML movement of the COP with the eyes open and closed,
      and the root-mean-square value of the ML displacement of COP were the indicators
      that showed significant associations with future falls. Measures related to
      dynamic posturography (moving platforms) were not predictive of falls.
      CONCLUSION: Despite a wide search only a few prospective follow-up studies using
      the force platform technique to measure postural balance and a reliable
      registration of subsequent falls were found. The results suggest that certain
      aspects of force platform data may have predictive value for subsequent falls,
      especially various indicators of the lateral control of posture. However, the
      small number of studies available makes it difficult to draw definitive
      conclusions.

PMID- 16439820
TI  - p53 and p66 proteins compete for hypoxia-inducible factor 1 alpha stabilization
      in young and old rat hearts exposed to intermittent hypoxia.
AB  - BACKGROUND: During development and aging, as well as under hypoxia, many cells
      can adapt to a stressful environment, while others are damaged and die by
      apoptosis. In particular, intermittent hypoxia, i.e., hypoxia followed by
      reoxygenation, determines different responses in young and adult myocardia.
      OBJECTIVE: In the rat myocardium exposed to hypoxia, the roles played by p53 and
      p66 Shc proteins in matching, in an age-dependent mode, in stabilizing hypoxia
      inducible factor-1alpha (HIF-1alpha), and in preventing its biological activity,
      which usually induces synthesis of rescue proteins against this stress, were
      investigated. METHODS: Five animals from three groups, each consisting of 10 male
      Wistar rats, 8 days and 3 and 24 months old, were kept under physiological
      conditions; 5 young and 5 old rats were exposed to intermittent hypoxic
      challenges (12 h at 10% O2 followed by 12 h at 21% O2) for 8 days. Pregnant rats
      were kept for 3 days under hypoxic conditions before delivery, and 5 neonate rats
      were kept in intermittent hypoxia for 8 days. Left ventricles were excised and
      processed for TUNEL and Western blotting analyses. RESULTS: HIF-1alpha
      stabilization by p53 along with decline in Bcl2, substantial caspase-3
      expression, and a large number of apoptotic events make the hypoxic young
      myocardium the most damaged when compared to the neonatal one, in which HIF
      1alpha is not stabilized. Moreover, high expression and activation of p66 in
      hypoxic young and in normoxic old myocardia suggests a pathological increase of
      the response to oxidative stress in the former and a physiological progressive
      increase in the latter. CONCLUSIONS: The different responses to hypoxic challenge
      during life show that the young seem the most reactive and damaged, as is well
      documented by p53-mediated HIF-1alpha stabilization. The neonate, not showing any
      modification in terms of HIF-1alpha expression and activation, seems 'adapted' to
      such an environment, since it was maintained in hypoxia 3 days before and 8 days
      after birth. In the old, increasing p66 expression and tyrosine phosphorylation,
      probably exerting a slight HIF-1alpha stabilization in the two experimental
      conditions, provide evidence of longevity and oxidative stress resistance, as
      suggested by the low number of apoptotic events seen upon hypoxic challenge, and
      this fact could be due to impairment of oxygen-sensing mechanisms or to
      adaptation of the cells to apoptosis.

PMID- 16439821
TI  - Comorbidity and physical function: results from the aging and longevity study in
      the Sirente geographic area (ilSIRENTE study).
AB  - BACKGROUND: Physical function measures have gained increased importance in the
      evaluation of older persons. The presence of comorbidity is a major and growing
      issue in geriatrics. OBJECTIVE: To evaluate the relationship between comorbidity
      and physical function in community-dwelling older persons. METHODS: Data are from
      baseline evaluation of the ilSIRENTE study (n = 364). Physical performance was
      assessed using the Short Physical Performance Battery (SPPB) and the 4-meter
      walking test. Muscle strength was measured by hand-grip strength. Functional
      performance was assessed using Basic and Instrumental Activities of Daily Living
      (ADLs and IADLs, respectively). Comorbidity was defined as >or=3 clinical
      conditions. Analyses of covariance and linear regressions were performed to
      evaluate the relationship between comorbidity and physical function. RESULTS: The
      mean age of participants was 85.9 (SD = 4.9) years. About one third (37.4%) of
      participants reported >or=3 clinical conditions. Participants with comorbidity
      had significantly worse results in all the physical function tests. Participants
      with comorbidity had significantly lower adjusted results for the 4-meter walking
      test (0.444 m/s) and the SPPB score (6.131) compared to those without comorbidity
      (0.531 m/s and 7.221; all p = 0.001, respectively). Participants with comorbidity
      were more IADL-impaired (3.152) than participants without comorbidity (2.767; p =
      0.04). No significant association of ADLs and hand-grip strength with comorbidity
      was reported. Similar strengths of association for the 4-meter walking test (per
      SD increase, beta = -0.280; p = 0.001) and the SPPB (per SD increase, beta = 
      0.285; p = 0.001) with comorbidity were reported. CONCLUSIONS: Physical function
      measures, especially walking speed and SPPB, are associated with comorbidity.
      Physical performance measures may improve the clinical evaluation of older
      persons.

PMID- 16439822
TI  - Seasonal variance in serum levels of vitamin d determines a compensatory response
      by parathyroid hormone: study in an ambulatory elderly population in Quebec.
AB  - BACKGROUND: Although the seasonal variance in serum levels of vitamin D in the
      elderly is well known, its significance on parathyroid hormone (PTH) remains
      controversial. OBJECTIVE: To identify the variability and correlation between
      serum levels of vitamin D and PTH in a sample of community-dwelling elderly
      patients in the Province of Quebec, Canada, where vitamin D and calcium are
      supplemented in the food. METHODS: Cross-sectional study in an ambulatory elderly
      population in the Province of Quebec. Samples were analyzed at the Metabolic and
      Calcium Research Centre, Royal Victoria Hospital, Montreal, Quebec. 256 healthy
      men and women aged 65-94 (mean age +/- SD: 72.8 +/- 5.6) were analyzed. Serum
      levels of 25-hydroxyvitamin D (25(OH)D3) and PTH were determined between 1994 and
      1999 using commercial radioimmunoassay kits to measure calciotropic hormones. We
      examined data in different seasons of the year and observed the behavior of the
      data through time. A cut-off level of 25 nmol/l for 25(OH)D3 was established to
      define vitamin D deficiency. A correlation between vitamin D levels vs. PTH
      levels was also obtained. RESULTS: There is a predominance of females with a 75%
      of the population. Among them, 32% showed levels of vitamin D <20 nmol/l as
      compared to 51% of the male population (p < 0.02). A seasonal variance in the
      levels of vitamin D was observed with the lower levels happening in early spring
      with a recovery at the end of the summer (p < 0.004). These low levels of vitamin
      D corresponded with an inverse pattern in the levels of PTH more importantly in
      early spring. CONCLUSION: This study not only confirms previous reports that
      despite vitamin D food supplementation a vitamin D deficiency is still a finding
      in elderly population in the Northern hemisphere, but also that a compensatory
      change in PTH levels concurrently occurs with a potential significance on bone
      strength and risk of fractures.

PMID- 16439823
TI  - Challenges and opportunities of health care for the aging community in Lithuania.
AB  - The aim of this paper is to present the Lithuanian experience in creating a
      geriatric care system with the hope that it can be of some use to other countries
      undergoing similar transitions and changes. The Lithuanian population is old with
      20% of the population being 60 years and older, and 15% being 65 years and older,
      with the trend toward a rapidly aging society. In 1990, Soviet rule in Lithuania
      ceased and the country regained its independence. With its recent acceptance into
      the European Union, the nation has set goals to meet the recommended requirements
      for the care of the elderly. The changes began with specialist training in
      gerontology and geriatrics, and were an essential first step to bridge the gap
      between the real and the future needs. Later, the Geriatric Care System
      Development Program was approved by the Ministry of Health. Despite its difficult
      past, Lithuania is confronting the challenges of health and social care of the
      aging population. It is embracing the opportunities to initiate policies and
      related measures to meet these challenges, and is potentially setting an example
      of good practice as a new European community.

PMID- 16439824
TI  - Pharmacokinetics of fluoxetine in elderly men and women.
AB  - Fluoxetine is widely prescribed as an antidepressant for geriatric patients.
      Despite a large scientific literature describing its efficacy and safety, there
      are few published data describing the pharmacokinetics of fluoxetine in the
      elderly. Given the common practice of polypharmacy in this population, additional
      pharmacokinetic information in elderly men and women is needed so that physicians
      can better assess potential drug-drug interactions. Twenty-five subjects, men and
      women between ages 65 and 83, received 20 mg of fluoxetine for 1 week followed by
      40 mg for 5 weeks. Serum fluoxetine levels were measured during the period of
      drug administration and for 8 weeks after. The plasma concentration of fluoxetine
      and norfluoxetine in our subjects was higher than previously reported in the
      literature. Elderly women had a significantly higher serum level of norfluoxetine
      than men. The terminal half-life of norfluoxetine was longer in patients over age
      75; elderly women had a significantly slower rate of norfluoxetine elimination
      than similarly aged men.

PMID- 16439825
TI  - Effect of age on the relationship of occupational social class with prevalence of
      modifiable cardiovascular risk factors and cardiovascular diseases. A population
      based cross-sectional study from European Prospective Investigation into Cancer -
      Norfolk (EPIC-Norfolk).
AB  - BACKGROUND: Previous studies on cardiovascular risk profile in different
      socioeconomic status were focused on younger populations and many of them have
      not been able to take into account age and sex differences. OBJECTIVES: To
      investigate the relationship of occupational social class with the prevalence of
      cardiovascular disease risk factors and cardiovascular diseases in younger (<65
      years) and older (>or=65 years) men and women. METHODS: A population-based-cross
      sectional study was conducted in a general community in Norfolk, United Kingdom.
      Participants were 23,085 men and women aged 40-79 years, recruited from general
      practice age-sex registers as part of European Prospective Investigation into
      Cancer-Norfolk (EPIC-Norfolk). The prevalence of cardiovascular risk factors and
      cardiovascular diseases were examined. RESULTS: The prevalence of smoking was
      significantly higher in those in manual social classes particularly in the
      younger (<65) age group. Younger women in manual social classes were more likely
      to be smokers compared to older women in the same social class. Being in manual
      social classes was associated with higher cholesterol levels in women but lower
      cholesterol levels in men. Manual social class was associated with higher
      physical activity in those younger than 65 years but this association was
      reversed in those 65 years or older. CONCLUSION: Occupational social class is
      differently related to cardiovascular risk factors in individuals depending on
      their age and sex. This may reflect differences in behavior at work and leisure,
      which vary by sex and pre- and postretirement. Interventions to promote health
      and reduce social inequalities need to take age and gender into account.

PMID- 16439826
TI  - Creativity with dementia patients. Can creativity and art stimulate dementia
      patients positively?
AB  - BACKGROUND: Creative activities could be stimulating for dementia patients. This
      article gives a review of practical forms of treating dementia patients with art
      therapeutic indications. It is also a ground for long-term research objective: in
      brief, I take exception to such a view, contrary to the common belief in the
      society and some professionals in the healthcare of dementia patients, on the
      ground that the patients do not have the capacity to improve their own
      creativity. METHODS: The theory of cognition tells us about the principle of
      being creative as a basis for human life. This specific principle is effective
      for the aged as well. In the long-term, the creative potential of old patients
      will be unblocked in individual and group therapy sessions. RESULTS: Creative
      activity has been shown to reduce depression and isolation, offering the power of
      choice and decisions. Towards the end of life, art and creativity offer a path of
      opening up the windows to people's emotional interiors. CONCLUSIONS: Creative-
      and art therapy provides possibilities that are mostly indicated to sharpen the
      capacity of the senses and the patients' propensity to act themselves. Nonverbal
      therapy methods, such as painting, music, etc., are able to influence the well
      being of the patients positively, within the modern healthcare system in nursing
      homes. The elderly and some of the dementia patients take the initiative to
      combine creativity and arts and to define his/her feeling for aesthetical
      matters. Furthermore, group therapy sessions help against isolation and lack of
      life perspective and hope.

PMID- 16439827
TI  - Factors related to institutionalization among the frail elderly with home
      visiting nursing service in Japan.
AB  - A dramatic increase in the number of elderly people in Japan has led to a
      concurrent increase in the number of frail elderly in need of care. It is
      estimated that the number of frail elderly will reach 3.9 million by the year
      2010. Family members are often both physically and mentally burdened with caring
      for the frail elderly. The present study was conducted to identify the risk
      factors for institutionalization among the frail elderly receiving in-home care
      in Japan.

PMID- 16439828
TI  - Left ventricular geometry in patients with obstructive sleep apnea coexisting
      with treated systemic hypertension.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy is a common consequence of systemic
      hypertension (SH) and obstructive sleep apnea (OSA). However, little is known
      about the degree of LV involvement in patients with OSA coexisting with treated
      SH. OBJECTIVES: Our study was designed in order to assess the prevalence of
      distinct types of LV geometry in treated hypertensive OSA patients. METHODS: 
      PATIENTS: 183 patients with treated SH were enrolled to the study. Group 1
      consisted of 38 patients with newly-diagnosed OSA and ineffectively treated SH.
      The remaining 145 patients with effectively treated SH were divided into three
      groups: group 2 - 70 patients with newly-diagnosed OSA, group 3 - 31 patients
      with OSA treated with continuous positive airway pressure (CPAP), and group 4 -
      44 patients without OSA. Overnight sleep studies and M-mode echocardiography were
      performed. RESULTS: LV mass index did not differ between the study groups. Mean
      values of LV end-diastolic diameter (LVED) were 55.4 +/- 6.8 mm in group 1 and
      53.6 +/- 6.9 mm in group 2 and were significantly increased in comparison to
      subjects treated with CPAP and controls (49.8 +/- 6.8 mm and 50.1 +/- 64.7 mm,
      respectively; p = 0.001). LVED correlated positively with the apnea-hypopnea
      index and desaturation index. LV eccentric hypertrophy was the commonest type of
      LV geometry in newly-diagnosed OSA patients. CONCLUSIONS: The major finding of
      our study is the predominance of LV eccentric hypertrophy in newly-diagnosed OSA
      patients. We suggest that a relatively moderate degree of LV involvement in
      hypertensive OSA patients may depend on the cardioprotective effect of
      concomitant antihypertensive therapy, ameliorating OSA-dependent neurohumoral
      abnormalities.

PMID- 16439830
TI  - Cochlear electrode arrays: past, present and future.
AB  - Cochlear implants are very successful devices: more than 60000 people use them
      throughout the world. Key to the success of these prostheses is the development
      of electrode arrays that place contacts close to the target neurons, survive for
      decades in the tissues of the inner ear, and that provide reliable and repeatable
      excitation to the cells of the auditory nerve. This article describes the early
      electrode arrays and their development into the arrays that are used presently in
      clinical cochlear prostheses. While integrated circuit techniques were proposed
      and tested in the laboratory two decades ago, the present clinical devices still
      are hand built and made of wire-based technologies. Current approaches that seek
      to automate the construction of cochlear electrode arrays are described and
      discussed.

PMID- 16439829
TI  - Incidence of venous thromboembolism in tuberculosis patients.

PMID- 16439831
TI  - The development of a biologically-inspired directional microphone for hearing
      aids.
AB  - The development of novel micro-fabrication techniques for producing a directional
      microphone for hearing aids is here described. The mechanisms underlying both the
      structure and function of these unusual microphones were originally inspired by
      the ears of an inconspicuous insect, the parasitoid fly Ormia ochracea. The
      structure of Ormia's ears inspired new approaches to design directional
      microphones that are more sensitive and have lower thermal noise than that
      typical of those using traditional approaches. The mechanisms for directional
      hearing in this animal are discussed along with the engineering design concepts
      that they have inspired, because they illustrate how basic research can inspire
      technology development-translational research. However, to realize the potential
      of bio-exploitation this microphone diaphragm concept would have been very
      difficult to realize without the availability of new silicon micro-fabrication
      technologies. Thus, this report can be viewed as an example of what may be
      possible with the application of new fabrication methods to microphones.
      Challenges and opportunities provided by the use of silicon micro-fabrication
      technology for microphones are discussed.

PMID- 16439832
TI  - Micromechanical resonator array for an implantable bionic ear.
AB  - In this paper we report on a multi-resonant transducer that may be used to
      replace a traditional speech processor in cochlear implant applications. The
      transducer, made from an array of micro-machined polymer resonators, is capable
      of passively splitting sound into its frequency sub-bands without the need for
      analog-to-digital conversion and subsequent digital processing. Since all bands
      are mechanically filtered in parallel, there is low latency in the output
      signals. The simplicity of the device, high channel capability, low power
      requirements, and small form factor (less than 1 cm) make it a good candidate for
      a completely implantable bionic ear device.

PMID- 16439833
TI  - Developing a physical model of the human cochlea using micro-fabrication methods.
AB  - Advances in micro-machining technology have provided the opportunity to explore
      possibilities of creating life-sized physical models of the cochlea. The physical
      model of the cochlea consists of two fluid-filled channels separated by an
      elastic partition. The partition is micro-machined from silicon and uses a 36-mm
      linearly tapered polyimide plate with a width of 100 microm at the basal end and
      500 microm at the apex to represent the basilar membrane. Thicknesses from 1 to 5
      microm have been fabricated. Discrete aluminum fibers (1.5 microm in width) are
      machined to create direction-dependent properties. A 0.5 x 0.5 mm opening
      represents the helicotrema. The fluid channels are machined from plexiglas using
      conventional machining methods. A magnet-coil system excites the fluid channel.
      Measurements on a model with thickness 4.75 microm show a velocity gain of 4 and
      phase of 3.5 pi radians at a location 23 mm from the base. Mathematical modeling
      using a 3-D formulation confirm the general characteristics of the measured
      response.

PMID- 16439834
TI  - An electronic prosthesis mimicking the dynamic vestibular function.
AB  - This paper presents a functional architecture, system level design, and
      electronic evaluation of a unilateral vestibular prosthesis. The sensing unit of
      the prosthesis is a custom-designed one-axis micro-electromechanical system
      (MEMS) gyroscope. Similar to the natural semicircular canal, the MEMS gyroscope
      senses angular motion of the head and generates voltages proportional to the
      corresponding angular acceleration. The voltage is then converted into electric
      current pulses according to the physiological data relating angular acceleration
      to the spike count in the vestibular nerve. The current pulses can be delivered
      to stimulate the corresponding vestibular nerve branch. Electronic properties of
      the vestibular prosthesis prototype have been systematically evaluated and found
      to meet the design specifications. A unique feature of the present vestibular
      implant prototype is the scalability: the sensing unit, pulse generator, and the
      current source can be potentially implemented on a single chip using integrated
      MEMS technology.

PMID- 16439835
TI  - Magnetic nanoparticles: inner ear targeted molecule delivery and middle ear
      implant.
AB  - Superparamagnetic iron oxide nanoparticles (SNP) composed of magnetite
      (Fe(3)O(4)) were studied preliminarily as vehicles for therapeutic molecule
      delivery to the inner ear and as a middle ear implant capable of producing
      biomechanically relevant forces for auditory function. Magnetite SNP were
      synthesized, then encapsulated in either silica or poly (D,L,-Lactide-co
      glycolide) or obtained commercially with coatings of oleic acid or dextran.
      Permanent magnetic fields generated forces sufficient to pull them across tissue
      in several round window membrane models (in vitrocell culture, in vivo rat and
      guinea pig, and human temporal bone) or to embed them in middle ear epithelia.
      Biocompatibility was investigated by light and electron microscopy, cell culture
      kinetics, and hair cell survival in organotypic cell culture and no measurable
      toxicity was found. A sinusoidal magnetic field applied to guinea pigs with SNP
      implanted in the middle ear resulted in displacements of the middle ear
      comparable to 90 dB SPL.

PMID- 16439836
TI  - Environmental micro-patterning for the study of spiral ganglion neurite guidance.
AB  - The projection of neuronal processes is guided by a variety of soluble and
      insoluble factors, which are sensed by a fiber's growth cone. It is the
      differential distribution of such guidance cues that determine the direction in
      which neurites grow. The growth cone senses these cues on a fine scale, using
      extensible filopodia that range from a few to tens of mum in length. In order to
      study the effects of guidance cues on spiral ganglion (SG) neurites, we have used
      methods for distributing both soluble and insoluble cues on a scale appropriate
      for sensing by growth filopodia. The scale of these methods are at the micro,
      rather than nano, level to match the sensing range of the growth cone.
      Microfluidics and transfected cells were used to spatially localize tropic
      factors within the fluid environment of extending neurites. Micro-patterning was
      used to present neurites with stripes of insoluble factors. The results indicate
      that differentially distributed permissive, repulsive and stop signals can
      control the projection of SG neurites. Implications for future micro-patterning
      studies, for SG development and for the growth of deafferented SG dendrites
      toward a cochlear implant are discussed.

PMID- 16439837
TI  - Non-puerperal uterine inversion due to uterine sarcoma.
AB  - BACKGROUND: Uterine inversion is a very rare pathological condition that usually
      occurs in puerperium. Non- puerperal uterine inversion is exceptional and to our
      knowledge only a few cases of uterine inversion due to a uterine sarcoma have
      been reported. CASE REPORT: A 79-year-old woman, gravida 0, para 0, presented
      with vaginal bleeding. Pelvic examination under anesthesia revealed a huge mass
      coming from the cervix filling the vagina to the introitus, and rectal
      examination could not identify the uterus. Diagnosis of uterine inversion was
      made and the patient was submitted to total abdominal hysterectomy with bilateral
      salpingo-oophorectomy and pelvic lymph node sampling. The postoperative course
      was uneventful and the patient was discharged on the 5th postoperative day. She
      underwent postoperative pelvic radiation, and no recurrence was found during the
      19-month follow-up period. CONCLUSION: Chronic non-puerperal uterine inversion
      can be considered a rare complication of malignant mixed mullerian tumor of the
      uterus.

PMID- 16439838
TI  - The developmental origins of insulin resistance.
AB  - Until recently, the principal causes of degenerative disease were thought to act
      in adult life and to accelerate destructive processes, such as the formation of
      atheroma and rise in blood pressure. Recent observations that people who develop
      coronary heart disease grow differently to other people during fetal life and
      childhood have, however, led to a new 'developmental' model for the disease. Low
      birthweight has been shown to be associated with increased rates of coronary
      heart disease, type 2 diabetes mellitus and altered glucose tolerance. These
      associations with low birthweight extend across the normal range of birthweight
      and reflect slow fetal growth rather than premature birth. The associations are
      thought to be consequences of developmental plasticity, the phenomenon by which
      one genotype can give rise to a range of different physiological or morphological
      states in response to different environmental conditions during development.
      Recent observations suggest that low birthweight, thinness at 2 years of age and
      an increase in body mass index (BMI) after the age of 2 years are each associated
      with the development of insulin resistance in later life. The prevention of a
      substantial proportion of type 2 diabetes and other disorders linked to insulin
      resistance may, therefore, depend on interventions during development. These
      include protecting the growth of babies during the first 2 years after birth by
      good infant feeding practices and preventing a rapid increase in BMI after the
      age of 2 years. Improving fetal nutrition remains an important long-term goal.

PMID- 16439839
TI  - Minimal model: perspective from 2005.
AB  - The minimal model was proposed over 25 years ago. Despite (or because of) its
      simplicity it continues to be used today - both as a clinical tool and an
      approach to understanding the composite effects of insulin secretion and insulin
      sensitivity on glucose tolerance and risk for type 2 diabetes mellitus. The
      original assumptions of the model have led to an understanding of the kinetics of
      insulin in vivo, as well as the relative importance of beta-cell compensatory
      failure in the pathogenesis of diabetes. The disposition index (DI), a parameter
      emerging from the model, represents the ability of the pancreatic islets to
      compensate for insulin resistance. There is evidence that a locus on chromosome
      11 codes for the DI, which has a significant heritability and can predict type 2
      diabetes better than any known genetic locus. Even today, the model continues to
      be a subject of scientific discovery and discourse.

PMID- 16439840
TI  - Clamp techniques in paediatrics: what have we learned?
AB  - The marked increase in conditions associated with insulin resistance in youth,
      including obesity, polycystic ovary syndrome, type 2 diabetes mellitus etc., has
      prompted the need to assess insulin sensitivity in this age group. Even though
      insulin resistance plays an important role in disorders of glucose metabolism and
      other pathological conditions, both insulin sensitivity and insulin secretion
      should be determined for a comprehensive evaluation of glucose homeostasis
      disorders. Insulin sensitivity and secretion are intricately coupled with a
      delicate feedback mechanism governing their relationship. This article will
      delineate our paediatric experience with the clamp technique, the
      hyperinsulinaemic-euglycaemic clamp in assessing in vivo insulin sensitivity, and
      the hyperglycaemic clamp in assessing insulin secretion.

PMID- 16439841
TI  - Simple fasting methods to assess insulin sensitivity in childhood.
AB  - The 'gold standard' techniques used to measure insulin sensitivity in children
      are the hyperinsulinaemic-euglycaemic clamp and Bergman's minimal model. Although
      precise, these techniques are complex, invasive and time consuming. Alternative
      indirect measures of insulin sensitivity have been developed that utilize fasting
      glucose and insulin data in algorithms or computer programs. These methods
      include homeostatic model assessment (HOMA), the quantitative insulin sensitivity
      check index (QUICKI) and the glucose to insulin ratio (G:I). Each of these three
      fasting techniques has been developed and validated in adults, with little or no
      validation in children. Increasingly, HOMA and QUICKI are being used in childhood
      studies to assess insulin sensitivity. In a group of 79 pre-pubertal children, we
      found that the correlation between the minimal model and RHOMA (r = -0.4) was no
      better than that between the minimal model and fasting insulin (r = 0.4), with an
      even weaker correlation between the minimal model and QUICKI (r = 0.2). In
      addition, neither HOMA nor QUICKI were able to detect a reduction in insulin
      sensitivity with obesity or during growth hormone therapy, unlike the minimal
      model. In children with normal glucose levels, neither HOMA nor QUICKI was
      superior to fasting insulin. Validation of the derivation formulae for these
      methods in children is needed before they are more widely used. The potential
      benefits of these simple fasting techniques is that they are useful in large
      field studies. However, if the study groups are small or longitudinal changes in
      insulin sensitivity are sought, more precise techniques such as the clamp or
      minimal model should be used.

PMID- 16439842
TI  - Use of stable isotopes to assess protein and amino acid metabolism in children
      and adolescents: a brief review.
AB  - As protein accretion is a prerequisite for growth, studying the mechanisms by
      which nutrients and hormones promote protein gain is of the utmost relevance to
      paediatric endocrinology. Tracers are ideally suited for the assessment of
      protein and amino acid kinetics in vivo, as they provide an estimate of synthesis
      and turnover. Current tracer approaches in children and adolescents utilize
      stable isotopes, 'heavier' forms of elements that have one or several extra
      neutrons in the nucleus. Such isotopes are already present at low, but
      significant, levels in all tissues and foodstuffs, are not radioactive and are
      devoid of any known side-effects when present in small amounts. L-[1-(13)C]
      labelled leucine, given as a 4- to 6-h intravenous infusion, has become the
      method of choice to assess whole-body protein kinetics. After infusion, any 13C
      leucine that is oxidized appears in the breath as 13CO2, whereas the remainder is
      incorporated into body proteins through protein synthesis. The isotope
      enrichments are determined by isotope ratio mass spectrometry and gas
      chromatography mass spectrometry, and absolute rates of whole-body protein
      synthesis, oxidation, and breakdown can be extrapolated. This approach has been
      used extensively to investigate the regulation of protein kinetics by nutrients
      and by hormones. Attempts have also been made to measure amino acid/protein
      metabolism in selected body compartments, and to measure the kinetics of specific
      tissue proteins, for example, muscle, gut, or plasma proteins.

PMID- 16439843
TI  - New imaging techniques of fat, muscle and liver within the context of determining
      insulin sensitivity.
AB  - Body fat distribution and ectopic fat deposition are important determinants of
      insulin sensitivity. Fat deposition in muscle and the liver, in particular, has
      been found to impair insulin signalling in these insulin-sensitive tissues. Thus,
      exact quantification of fat content may help to distinguish between different
      sites of insulin resistance. Increased fat deposition in the visceral compartment
      compared with the subcutaneous depot also represents an important factor leading
      to insulin resistance. Recent data clearly showed that visceral fat is a strong
      determinant of liver fat content. Exact quantification of fat distribution by
      magnetic resonance imaging and magnetic resonance spectroscopy may help to define
      distinct 'fat-distribution phenotypes'. This may allow a search for new candidate
      genes for type 2 diabetes mellitus and identify, at an early stage, individuals
      at risk for decline in insulin sensitivity.

PMID- 16439844
TI  - Insulin sensitivity in adults with growth hormone deficiency and effect of growth
      hormone treatment.
AB  - Adult growth hormone deficiency (GHD) is a multifactorial disorder in which
      pituitary dysfunction associated with pituitary adenomas or their treatment plays
      a major role. The introduction of recombinant growth hormone (GH) for the
      treatment of GHD has opened up new treatment avenues but has also raised concerns
      about possible untoward long-term metabolic effects of GH, such as the potential
      effect of GH on insulin sensitivity and a deterioration in glucose tolerance.
      Research has shown that GH induces insulin resistance by the stimulation of
      lipolysis and a concomitant switch from oxidation of glucose to oxidation of
      lipids, during both acute and chronic treatment. However, although this is a
      consistent effect of GH therapy, it does not mean per se that it leads to
      abnormal glucose tolerance and diabetes mellitus. This article discusses this and
      other potential long-term metabolic effects of GH, and raises a number of
      questions to be addressed by future research.

PMID- 16439845
TI  - Turner syndrome, insulin sensitivity and growth hormone treatment.
AB  - Mild insulin resistance appears to be an early metabolic defect in girls with
      Turner syndrome (TS). Impaired glucose tolerance has been reported in 10-34% of
      patients with TS, and type 2 diabetes mellitus is 2-4 times more common and
      occurs at a younger age in girls with TS than in the general population. In a
      mixed longitudinal and cross-sectional study, we analysed carbohydrate tolerance
      and insulin sensitivity in 46 children and adolescents with TS who reached their
      final height after long-term treatment (mean 6.3 +/- 2.5 years) with growth
      hormone (GH: 0.33 mg/kg/week [0.05 mg/kg/day]), and in 36 of these patients who
      were followed-up after the cessation of GH therapy (mean follow-up, 2.6 +/- 2.5
      years; range, 1-9.5 years). Patients with TS were compared with an age-matched
      female control group. Insulin sensitivity appeared to be lower in patients with
      TS than in controls, even before the start of GH therapy. As in controls, insulin
      sensitivity decreased with age in patients with TS, and levels were lower in
      those aged >12 years than in those aged <12 years. GH therapy resulted in good
      catch-up growth in patients with TS, with final height significantly higher than
      projected height evaluated before the initiation of GH therapy. Insulin
      sensitivity increased after 7-8 years of therapy and, on the cessation of GH
      therapy, returned to pre-treatment levels. The increase in insulin sensitivity
      seen on the cessation of GH therapy appeared to be influenced negatively by body
      mass index and triglyceride levels, and correlated positively with the number of
      years since cessation of GH therapy. As in the general population, excess weight
      and an abnormal lipid profile, in particular excess triglyceride levels, worsened
      insulin sensitivity. In conclusion, our study confirms that GH therapy reduces
      insulin sensitivity, but at its cessation there is a return to pre-therapy
      values. We therefore report a progressive improvement in carbohydrate tolerance
      and insulin function in patients with TS, despite an increase in age.

PMID- 16439846
TI  - Babies born small for gestational age: insulin sensitivity and growth hormone
      treatment.
AB  - Epidemiological studies have identified an association between size at birth and
      adult risk for type 2 diabetes mellitus and cardiovascular disease. In
      contemporary populations, children who are relatively small at birth and show
      rapid infancy weight gain are at greatest risk for the development of childhood
      obesity, increased visceral fat and insulin resistance: possible early markers of
      adult disease risk. Individuals presenting to growth clinics with short stature
      and a history of low birthweight will not have shown post-natal catch-up growth
      and may be a very heterogeneous group. Nevertheless, there are some data to
      suggest that as a group they are insulin resistant with decreased lean mass.
      Growth hormone treatment leads to reversible worsening of the insulin resistance,
      and short-term data do not indicate an increased risk for type 2 diabetes.
      However, further long-term follow-up is required, and particular care should be
      taken in monitoring children with a strong family history of type 2 diabetes and
      those from ethnic groups in which there is a high background prevalence of the
      disease.

PMID- 16439847
TI  - The role of growth hormone in neural development.
AB  - Growth hormone (GH) is integrally involved in the development of the central
      nervous system (CNS), as well as during its recovery from injury, two processes
      that share many similarities and may influence CNS functionality. This review
      discusses some of the most recent findings in the field and, in particular, the
      ontogeny, distribution, regulation and putative functions of GH and its receptor
      within the CNS, particularly during development. The relative roles of peripheral
      GH, acting in part through insulin-like growth factor-I, and of the
      autocrine/paracrine GH system within the brain are considered. The potential role
      of GH as a therapeutic agent to influence brain development and function is
      discussed.

PMID- 16439848
TI  - Measuring social-cognitive functions in children with somatotropic axis
      dysfunction.
AB  - Growth hormone (GH) and insulin-like growth factor I (IGF-I) are expressed in
      specific regions of the central nervous system during early human development.
      They may consequently influence aspects of cognition, or emotional and
      behavioural adjustment from childhood to adulthood, in conditions associated with
      abnormalities of the somatotropic axis. GH receptors are relatively common within
      hippocampal and perihippocampal regions that are primarily involved in
      declarative memory for facts and events. They are also located in structures
      (e.g. the putamen) that are involved in the processing of social perceptions. IGF
      I receptors have been discovered in the amygdala and prefrontal cortex, which
      contribute to the neural circuits known as the 'social brain'. The evaluation of
      emotional, social and behavioural adjustment among children who have deficiencies
      in GH or IGF-I functional integrity requires the objective assessment of their
      social-cognitive competence. We describe a computerized test battery, the
      Schedules for the Assessment of Social Intelligence (SASI), which has been shown
      to possess excellent psychometric properties in terms of reliability and
      validity. The SASI, which can be used by both children and adults, may provide
      new evidence for deficits and treatment effects of GH/IGF-I on emotional,
      behavioural and cognitive functions.

PMID- 16439849
TI  - Neurocognitive development in children experiencing intrauterine growth
      retardation and born small for gestational age: pathological, constitutional and
      therapeutic pathways.
AB  - Interest in the neurocognitive and psychosocial outcomes in children who are born
      small for gestational age (SGA) has increased since the recent approval of growth
      hormone (GH) therapy in this indication. The objective of GH treatment in SGA
      children is to provide a symptomatic treatment for growth retardation. From a
      patient perspective, the ultimate goals of GH therapy are the reduction in the
      present or future risk of neurocognitive, psychological, social or occupational
      impairment, not the accompanying improvements in growth velocity and final height
      per se. Therefore, from a scientific perspective, neurocognitive and psychosocial
      endpoints become relevant domains of assessment to determine the final treatment
      benefit experienced by the patient born SGA. This article reviews recent
      available studies on developmental risks in SGA, and then transforms the
      empirical findings into an integrated conceptual framework on the sources and
      mediators of neurocognitive and psychosocial outcomes in intrauterine growth
      retardation and SGA. This framework depicts two distinct therapeutic pathways by
      which GH therapy may improve neurocognitive and behavioural outcomes. The first
      ('traditional') pathway is the prevention of exposure to short-stature-related
      stressors via an improvement in growth velocity and final height. The second
      pathway refers to potential metabolic, and thus neurotropic and psychotropic,
      effects of GH binding at receptors in the central nervous system, thus changing
      neuronal activity. To date, the existence and potential mechanisms of such
      physiologically and not psychologically mediated effects of GH on neurocognitive
      functioning in SGA patients remain hypothetical.

PMID- 16439850
TI  - Effects of growth hormone on cognitive function.
AB  - Whether growth hormone deficiency (GHD) and/or treatment in childhood and
      adolescence influences cognitive outcome in children with GHD or girls with
      Turner syndrome (TS) is controversial. Previous studies also suggest that quality
      of life (QoL) is reduced in adults with GHD, particularly in the areas of social
      isolation and fatigue. Baseline QoL scores were significantly lower in patients
      with GHD than in the general population of the same age, gender, and nationality.
      Unfortunately, few data are available describing QoL in children with GHD. TS is
      a genetic disorder characterized by short stature, gonadal dysgenesis, and a
      particular neurocognitive profile of normally developed language abilities
      (particularly verbal intelligence quotients) and impaired visual-spatial and/or
      visual-perceptual abilities. This study evaluated the effects of GH treatment on
      neurocognitive function in girls with TS who were enrolled in a long-term, double
      blind, placebo-controlled trial of the effects of GH treatment on final adult
      height. Treatment duration ranged from 1 to 7 years. The major result of this
      study was the absence of GH treatment effects on cognitive function in girls with
      TS. GHD and/or treatment in childhood and adulthood influences cognitive and/or
      QoL outcomes in some but not all studies. This study did not support a role for
      GH in influencing the characteristic nonverbal neurocognitive deficits associated
      with TS. However, evaluation of QoL should be a part of the routine clinical
      management of patients with GHD or TS.

PMID- 16439851
TI  - Effects of growth hormone treatment on cognitive function and head circumference
      in children born small for gestational age.
AB  - Short stature is not the only problem faced by children born small for
      gestational age (SGA). Being born SGA has also been associated with lowered
      intelligence, poor academic performance, low social competence and behavioural
      problems. This paper summarizes the results of a randomized, double-blind, growth
      hormone (GH) dose-response study (1 or 2 mg/m2/day [ approximately 0.035 or 0.07
      mg/kg/day]) on growth, intelligence quotient (IQ) and psychosocial functioning in
      79 children born SGA at the start, and after 2 and 8 years of GH therapy, and
      addresses the associations with head circumference. Mean age at start of therapy
      was 7.4 years; mean duration of GH treatment was 8.0 years. In 2001, 91% of
      children born SGA had reached a normal height (> -2.0 standard deviation score
      [SDS]). Block-design s-score (Performal IQ) and Total IQ score increased (p <
      0.001 for both indices) from scores significantly lower than those of Dutch peers
      at the start of therapy (p < 0.001) to scores that were comparable to those of
      Dutch peers in 2001. Vocabulary s-score (Verbal IQ) was normal at the start of
      therapy and remained so over time. Externalizing Problem Behaviour SDS and Total
      Problem Behaviour SDS improved during GH therapy (p < 0.01-0.05) to scores
      comparable to those of Dutch peers. Internalizing Problem Behaviour SDS was
      comparable to that of Dutch peers at the start of therapy and remained so,
      whereas Self-Perception improved from the start of GH therapy until 2001 (p <
      0.001), when it reached normal scores. Head circumference SDS at the start of GH
      therapy and head growth during GH therapy were positively related to all IQ
      scores (p < 0.01), whereas neither were related to height SDS at the start of, or
      to its improvement during, GH therapy. A significant improvement in height and
      head circumference in children born SGA was seen after only 3 years of GH
      therapy, in contrast to randomized SGA controls. In conclusion, most children
      born SGA showed a normalization of height during GH therapy and, in parallel to
      this, a significant improvement in Performal IQ and Total IQ. In addition,
      problem behaviour and self-perception improved significantly. Interestingly,
      Performal, Verbal and Total IQ scores were positively related to head
      circumference, both at the start of, and during, GH therapy; head circumference
      increased in GH-treated children born SGA, but not in untreated SGA controls.
      These results are encouraging but also warrant confirmational studies and further
      investigations into the effects of GH on the central nervous system.

PMID- 16439852
TI  - Cognitive function in growth hormone deficiency and growth hormone replacement.
AB  - There is converging evidence from neuropsychological studies that growth hormone
      (GH) is associated with cognitive function. The aim of the current study was to
      review the existing neuropsychological literature for studies in which cognitive
      assessment had been conducted in patients with GH deficiency (GHD), and where
      change in cognitive function had been assessed following treatment with GH.
      Studies that have investigated relationships between GH and cognitive function
      and those that have developed methodological and statistical approaches that
      could be useful in future GH studies were identified. In this review, GH levels
      were found to be associated with cognitive function. Untreated individuals with
      GHD showed reliable impairment in memory and attentional functions when compared
      with matched controls. Appropriately designed prospective studies also indicated
      that cognitive function improved with GH treatment. It was concluded that
      individuals with GHD do show cognitive impairment and that this is ameliorated to
      some extent by GH treatment. It is now important to establish the clinical
      importance of these findings, and further work is required to understand better
      the nature, magnitude and meaning of GH-related cognitive impairments and
      improvements.

PMID- 16439853
TI  - Neurocognitive function in adults with growth hormone deficiency.
AB  - The clinical condition of growth hormone deficiency (GHD) as a consequence of
      pituitary or hypothalamic disease has been associated with reduced cognitive
      performance. In several studies, neuropsychological assessment has been performed
      in adults with GHD both before and after growth hormone (GH) replacement therapy.
      Interpretation of the available data is complicated by the variation in patient
      selection as well as the neuropsychological tests used in such studies. Most of
      the available studies indicate that GHD can lead to small, but clinically
      relevant changes in memory, processing speed and attention. Some of these changes
      may be reversed by GH replacement, although the number of reliable intervention
      studies is limited. In addition to the possible clinical relevance of
      neuropsychological improvement following GH replacement in patients with GHD, the
      observed findings may be of interest for studies in neurocognitive performance in
      other conditions associated with changes in the activity of the somatotrophic
      axis, and in the understanding of underlying pathophysiological mechanisms.

PMID- 16439854
TI  - Idiopathic premature ovarian failure in 63 young women.
AB  - BACKGROUND: Premature ovarian failure (POF) in adolescents is defined as primary
      or secondary amenorrhea associated with high follicle-stimulating hormone (FSH)
      levels. In normal 46,XX patients, its etiology is most often unknown. We have
      evaluated the clinical, hormonal and ovarian phenotypes in patients with a normal
      karyotype who were diagnosed with POF before the age of 18. METHODS: Sixty-three
      patients were included in this retrospective study. RESULTS: The mean patient age
      was 20.4 years. The patients presented with three clinical patterns: lack of
      pubertal development (n = 23), primary amenorrhea with interrupted puberty (n =
      18), and secondary amenorrhea with normal puberty (n = 22). Ten patients had a
      familial history of POF and 6 presented with hypothyroidism. The FSH, estradiol
      and inhibin B levels were not statistically different in the three clinical
      groups. Fifty percent of the patients presented small ovaries (length <2 cm) at
      ultrasonography. The presence of follicles was found at histology in only 7 of
      the 27 patients who underwent an ovarian biopsy. CONCLUSION: 46,XX patients
      presenting with early POF rarely presented a specific, identifiable disorder. We
      discuss the clinical management and different diagnosis strategies to improve our
      current knowledge of this syndrome.

PMID- 16439855
TI  - Prophylactic intranasal treatment with fragments of 1,3-beta-glucanase olive
      pollen allergen prevents airway inflammation in a murine model of type I allergy.
AB  - BACKGROUND: Olive pollen is an important cause of allergy in Mediterranean
      countries. More than 50% of olive-pollen-allergic patients are sensitized against
      the 1,3-beta-glucanase Ole e 9. To date, prophylactic and therapeutic treatments
      using purified recombinant allergens have not been studied in animal models of
      olive pollen allergy. METHODS: BALB/c mice were immunized against Ole e 9
      combining intraperitoneal injections of the allergen in Al(OH)3 with airway
      allergen challenges. A prophylactic treatment was performed by intranasal
      administration of a mixture of the recombinant fragments of the allergen prior to
      Ole e 9 sensitization. Serum levels of specific IgE, IgG1, IgG2a and IgG2b were
      measured by ELISA, and total IgE levels by sandwich ELISA. Bronchoalveolar lavage
      and lungs from mice were collected to study airway inflammation by light
      microscopy. RESULTS: BALB/c mice immunized against Ole e 9 developed a
      predominantly Th2-like immune response with allergen-specific immunoglobulin
      induction and airway inflammation accompanied by the infiltration of eosinophils,
      lymphocytes, and neutrophils in the lung. Prophylactic treatment by intranasal
      application of the recombinant fragments of Ole e 9 avoids airway inflammation
      induced by sensitization with this allergen although the levels of Ole e 9
      specific antibodies remain unchanged. CONCLUSIONS: Prophylactic intranasal
      treatment with recombinant fragments of Ole e 9 prevents airway inflammation
      triggered by immunization to this allergen in a murine model of type I allergy.

PMID- 16439856
TI  - Glycosylation of recombinant proforms of major house dust mite allergens Der p 1
      and Der f 1 decelerates the speed of maturation.
AB  - BACKGROUND: The efficient manufacture of recombinant Der p 1 and Der f 1 has been
      an important bottleneck in the study of house dust mite allergies and the
      development of applications for allergen engineering. While Der f 1 has only one
      N-glycosylation motif in the mature sequence, Der p 1 has two motifs, one in the
      prosequence and the other in the mature sequence. To test whether inefficient
      maturation of a recombinant Pro-Der p 1 versus Pro-Der f 1 is due to N
      glycosylation, the maturation speed of N-glycosylation motif mutants was
      compared. METHODS: Expression vectors for the mutants, in which the motif in the
      Der p 1 prodomain was disrupted or a motif was created within the Der f 1
      prodomain, were constructed by site-directed mutagenesis of preproforms with or
      without the motif within the mature portion. Culture supernatants of yeast Pichia
      pastoris transfectant cells containing proforms were buffer exchanged by gel
      filtration and incubated for maturation. Samples from the reactions were
      collected every 20 min and subjected to electrophoresis. The maturation speed was
      compared based on the band densities of the pro- and mature forms. RESULTS:
      Disruption of the motif in the mature portion decreased the productivity and
      accelerated the maturation. Maturation was also accelerated by disruption of the
      other motif in the Der p 1 prodomain and slowed down by introduction of the motif
      into the Der f 1 prodomain. CONCLUSIONS: Maturation systems using Pro-Der p 1
      without the prodomain glycosylation are useful for the efficient preparation of a
      recombinant mature allergen. In addition, these results demonstrated that the
      maturation of cysteine protease could be controlled through glycosylation of the
      prodomain.

PMID- 16439857
TI  - Toll-like receptor ligands reverse suppression of contact hypersensitivity
      reactions induced by epicutaneous immunization with protein antigen.
AB  - BACKGROUND: Epicutaneous (EC) immunization with protein antigens has been shown
      to induce antigen nonspecific suppression of subsequent T cell-dependent contact
      hypersensitivity (CS) reactions after active immunization. The aim of this work
      was to test if EC application of Toll-like receptor (TLR) ligands together with
      protein antigen could reverse suppression of CS. METHODS: Mice were EC immunized
      by applying gauze patches soaked with a solution of protein antigen alone or in
      the presence of crude bacterial material (bacterial lysates or heat-killed
      bacteria) or purified TLR ligands and then tested for CS response. To test if
      reversal of EC-induced suppression is antigen-specific, mice were patched with
      TNP- or OX-substituted mouse Ig alone or together with LPS and then tested for CS
      with corresponding or non-cross-reacting hapten. Influence of EC immunization on
      cytokine production by lymph node cells was measured by ELISA. RESULTS: EC
      immunization with protein antigen induces antigen nonspecific suppression that
      can be reversed by crude bacterial material as well as purified TLR-2, TLR-3, TLR
      4, and TLR-9 ligands. The effect of TLR-4 ligand LPS was not observed in the Tlr
      4 mutant C3H/HeJ mouse, indicating that this effect was dependent upon intact TLR
      4 signaling. Unlike the antigen nonspecific suppression of CS by EC immunization
      with antigen alone, the reversal of suppression by TLR ligands was specific for
      the protein antigen applied in the EC protocol. CONCLUSIONS: Our results strongly
      suggest that EC immunization with protein antigen together with TLR ligands
      induces a particular antigen-specific cell population, akin to previously
      described contrasuppressor cells, which protects immune cells against the action
      of suppressor cells but have no direct influence on antigen nonspecific
      suppressor cells induced by antigen alone.

PMID- 16439858
TI  - Study of IgE antigenic relationships in hypersensitivity to hydrolyzed wheat
      proteins and wheat-dependent exercise-induced anaphylaxis.
AB  - BACKGROUND: Wheat is involved in different forms of respiratory, food and contact
      allergy. The IgE of patients generally reacts with various flour proteins. It is
      not known if antigenic relationships could explain some of these reactions and if
      proteins could be involved in different pathologies. METHODS: Two sera were
      selected as representative of patients with either wheat-dependent exercise
      induced anaphylaxis (WDEIA) or hypersensitivity to hydrolyzed wheat proteins
      (HHWP). Their IgE specificity was studied with wheat, barley and rye proteins,
      using immunoblot, and immunoblot inhibition with recombinant gamma-3 hordein.
      This protein was chosen for its cross-reactivity with omega-5 gliadin, a major
      allergen in WDEIA. RESULTS: The IgE from both sera strongly reacted with natural
      and recombinant gamma-3 hordein but displayed different patterns of reactivity
      with wheat, barley and rye proteins. Those from the WDEIA patient showed expected
      reactions with omega-5 gliadin, gamma-35 and gamma-75 secalins, but also with
      wheat low-molecular-weight glutenin subunits (LMW-GS), and not with C hordeins.
      On the contrary, IgE from a HHWP patient reacted with C hordeins, various omega
      gliadins, and gamma-75 secalin, but very weakly with gamma-35 secalin and LMW-GS.
      Recombinant gamma-3 hordein inhibited strongly but not totally the WDEIA
      patient's IgE binding to prolamins. No such inhibition could be observed for the
      HHWP patient's IgE. CONCLUSIONS: At least part of the reactions of prolamins with
      the IgE from the WDEIA patient was due to antigenic homologies. The occurrence of
      cross-reacting carbohydrates was unlikely. These common IgE epitopes were not
      involved in the pathology of the HHWP patient.

PMID- 16439859
TI  - Occupational exposures and movement abnormalities among Japanese-American men:
      the Honolulu-Asia Aging Study.
AB  - OBJECTIVE: The authors analyzed data on 1,049 men aged 71-93 years (excluding
      those with prevalent Parkinson's disease and stroke) from the Honolulu Heart
      Program (1965-1968) and the Honolulu-Asia Aging Study (1991-1999) to determine
      whether occupational exposures to pesticides, solvents, metals, manganese, and
      mercury during middle age were associated with 14 movement abnormalities 25 years
      later. METHODS: Analyses of variance and multivariate logistic regression were
      used to assess associations of interest. RESULTS: After adjustment for age, BMI,
      cognitive functioning, smoking, alcohol drinking, education, and physical
      activity, there was a positive association between abnormal 'facial expression'
      and the highest exposure to metals [odds ratio (OR) = 2.62; 95% confidence
      interval (CI) = 1.35-5.11; trend, p = 0.02], and the highest exposure to mercury
      (OR = 1.91; 95% CI = 1.04-3.49; trend, p = 0.03). Age was positively associated
      with all movement abnormalities, and cognitive function, body mass index and
      physical activity were inversely associated with most movement abnormalities.
      CONCLUSION: Higher exposure to any metal, and specifically mercury, was
      associated with abnormal facial expression.

PMID- 16439860
TI  - Role of anastrozole across the breast cancer continuum: from advanced to early
      disease and prevention.
AB  - Breast tumorigenesis is a continuum from preinvasive lesions to early breast
      cancer and advanced disease. In this article the data supporting the use of the
      aromatase inhibitor anastrozole in postmenopausal women across this continuum are
      reviewed. In advanced disease, anastrozole has a significant survival benefit and
      tolerability advantage compared with megestrol acetate when used as second-line
      treatment. As first-line therapy, anastrozole significantly prolongs time to
      progression compared with tamoxifen in women with hormone receptor-positive (HR+)
      disease. In the adjuvant setting, anastrozole has superior efficacy and
      tolerability compared with tamoxifen in newly diagnosed patients and those who
      have already received 2-3 years' prior adjuvant tamoxifen. Therefore, anastrozole
      should be considered a preferred treatment option for postmenopausal women with
      HR+ early breast cancer. Furthermore, anastrozole has preoperative efficacy in
      HR+ large or locally advanced tumors. Finally, anastrozole substantially reduces
      the incidence of contralateral breast cancer compared with tamoxifen in women
      with HR+ early breast cancer and, therefore, is a potential chemopreventive
      agent. Anastrozole is thus positioned to become the standard care for
      postmenopausal women with HR+ disease across the whole breast cancer continuum.
      Additional data from ongoing studies will further clarify the role of anastrozole
      across the continuum and answer outstanding questions regarding the optimal
      timing and duration of treatment.

PMID- 16439861
TI  - Perillyl alcohol induces c-Myc-dependent apoptosis in Bcr/Abl-transformed
      leukemia cells.
AB  - Bcr/Abl-transformed cells strongly resist apoptosis induced by most chemotherapy
      agents. However, in Bcr/Abl-transformed cells the monocyclic monoterpene,
      perillyl alcohol (POH), induces G0/G1 arrest and apoptosis without affecting
      Bcr/Abl expression or activity. The primary effect of POH is to cause growth
      arrest while apoptosis is a consequence of this arrest. Since Bcr/Abl induces
      constitutive expression of c-Myc, which is necessary for cell cycle transit from
      G1 into the S phase, we tested whether POH causes growth arrest by inhibiting
      expression of c-Myc. However, in POH-arrested Bcr/Abl-transformed cells,
      expression of c-Myc RNA and protein was not affected. Because expression of c-Myc
      during growth arrest can lead to apoptosis, we examined the role of c-Myc in POH
      induced apoptosis. c-Myc induces expression of the ornithine decarboxylase (ODC)
      gene, which synthesizes polyamines that are necessary for cell growth. Myc
      induced apoptosis operates through ODC and can be prevented with the ODC
      inhibitor, alpha-difluoromethylornithine (DFMO). We report that DFMO strongly
      protects cells from POH-induced apoptosis. These results show that in Bcr/Abl
      transformed cells, POH activates a Myc-ODC apoptotic pathway that is not
      protected by the Bcr/Abl antiapoptotic mechanism.

PMID- 16439863
TI  - Hepatitis Cs effect on HIV disease remains elusive despite three new studies.

PMID- 16439862
TI  - A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent
      external and endocavitary radiation therapy in locally advanced or recurrent
      cervical cancer.
AB  - BACKGROUND: Five randomized studies have demonstrated a beneficial effect of
      adding cisplatin-based chemotherapy to radiation therapy in the treatment of
      cervical carcinoma. In the present phase II study, we evaluated the response and
      toxicity of cisplatin-Taxol chemotherapy combined with concomitant radiotherapy
      in patients with locally advanced cervical carcinoma (LACC) and locally recurrent
      cervical carcinoma (LRCC). PATIENTS AND METHODS: In 2000, this phase II study was
      initiated with a chemotherapy regimen of cisplatin (75 mg/m(2)) and Taxol (175
      mg/m(2)) every 21 days, for four cycles, concomitant with external radiotherapy
      and high-dose-rate brachytherapy. Pelvic radiotherapy was started 2 weeks after
      the first chemotherapy cycle, while the first brachytherapy insertion was carried
      out during the fourth chemotherapy cycle. SCC marker was determined before
      treatment and after every chemotherapy cycle. RESULTS: All of the 27 patients
      treated achieved a complete clinical response. Two patients with LACC experienced
      distant recurrence 22 and 24 months after complete response, respectively, and 1
      patient with LRCC had local progression 6 months after the end of radiotherapy.
      Although generally tolerable, neutropenia grade 3-4 in 4 patients and anemia
      grade 3 in 2 patients were observed, and 1 patient experienced grade 2
      neurotoxicity; toxicity due to radiotherapy was moderate. CONCLUSIONS:
      Concomitant cisplatin-Taxol chemoradiotherapy seems to be well tolerated, and
      results, even in this small series, are encouraging.

PMID- 16439864
TI  - Kuru experiments triggered the emergence of pathogenic SIVmac.

PMID- 16439865
TI  - Hepatitis C coinfection is independently associated with decreased adherence to
      antiretroviral therapy in a population-based HIV cohort.
AB  - OBJECTIVE: To characterize the impact of hepatitis C (HCV) serostatus on
      adherence to antiretroviral treatment (ART) among HIV-infected adults initiating
      ART. METHODS: The British Columbia HIV/AIDS Drug Treatment Program distributes,
      at no cost, all ART in this Canadian province. Eligible individuals used triple
      combination ART as their first HIV therapy and had documented HCV serology.
      Statistical analyses used parametric and non-parametric methods, including
      multivariate logistic regression. The primary outcome was > or = 95% adherence,
      defined as receiving > or = 95% of prescription refills during the first year of
      antiretroviral therapy. RESULTS: There were 1186 patients eligible for analysis,
      including 606 (51%) positive for HCV antibody and 580 (49%) who were negative. In
      adjusted analyses, adherence was independently associated with HCV seropositivity
      [adjusted odds ratio (AOR), 0.48; 95% confidence interval (CI), 0.23-0.97; P =
      0.003], higher plasma albumin levels (AOR, 1.07; 95% CI, 1.01-1.12; P = 0.002)
      and male gender (AOR, 2.53; 95% CI, 1.04-6.15; P = 0.017), but not with injection
      drug use (IDU), age or other markers of liver injury. There was no evidence of an
      interaction between HCV and liver injury in adjusted analyses; comparing
      different strata of HCV and IDU confirmed that HCV was associated with poor
      adherence independent of IDU. CONCLUSIONS: HCV-coinfected individuals and those
      with lower albumin are less likely to be adherent to their ART.

PMID- 16439866
TI  - A novel soluble mimic of the glycolipid, globotriaosyl ceramide inhibits HIV
      infection.
AB  - OBJECTIVE: To determine the effect of a gp120 binding, non-cytotoxic soluble
      analogue of the glycosphingolipid (GSL), globotriaosyl ceramide (Gb3) on HIV
      infection in vitro. DESIGN: HIV-1(IIIB) (X4 virus) infection in Jurkat and
      phytohaemagglutinin (PHA)/interleukin-2 (IL2) activated, peripheral blood
      mononuclear cells (PBMC), and HIV-1(Ba-L) (R5 virus) infection of PHA activated
      PBMC in vitro were assessed. We monitored cell surface markers, cell viability,
      and viral/host cell morphology to eliminate pleiotropic effects. Viral-host cell
      fusion was measured to further address any inhibitory mechanism. METHODS: HIV
      infection was monitored by p24(gag) ELISA. CD4, CCR5, CXCR4 and apoptosis were
      determined by fluorescent antibody cell sorting. A model fusion system comprising
      a cell line transfected with either CD4 and CXCR4 or CCR5, cocultured with a cell
      line expressing gp120 from either X4-, R5-tropic HIV-1 or HIV-2 virions, was
      used. PHA/IL2 activated PBMC GSL synthesis was monitored by metabolic
      radiolabelling. RESULTS: AdamantylGb3 blocked X4 and R5 virus infection with a
      50% inhibitory concentration of approximately 150 microM. A reverse transcriptase
      and a protease-resistant X4 HIV-1 strain retained adamantylGb3 sensitivity.
      AdamantylGb3 had minimal effect on cell viability. Treated Jurkat cells showed a
      small increase in CCR5/CXCR4 expression and a slight, transient CD4 down
      regulation, which was probably not related to the mechanism of inhibition.
      Electron microscopy showed normal viral and host cell morphology following
      adamantylGb3 treatment, and viral entry was blocked. AdamantylGb3 was able to
      prevent virus-host cell fusion irrespective of HIV strain or chemokine receptor
      preference. CONCLUSIONS: These results suggest that adamantylGb3 may provide a
      new basis for blocking HIV infections, irrespective of HIV envelope/chemokine co
      receptor preference or resistance to other therapeutics.

PMID- 16439868
TI  - Group M-based HIV-1 Gag peptides are frequently targeted by T cells in
      chronically infected US and Zambian patients.
AB  - BACKGROUND: The enormous sequence diversity of HIV-1 has been a major obstacle in
      the development of a globally useful vaccine for AIDS. The consensus and
      ancestral sequence-based immunogens minimize the genetic distance between
      contemporary isolates and vaccine strains. Hence these sequences may be promising
      candidates for HIV vaccines or serve as a universal reagent set for evaluating
      Gag-specific responses. METHODS: In this study, we measured the T-cell reactivity
      to consensus (subtype A, B, C and group M), ancestral (group M and subtype B) and
      HXB2 Gag peptides (15-mers overlapping by 11) in HIV-1-infected subjects from two
      reference populations. We evaluated the Gag-specific T-cell responses in 43
      chronically infected US (subtype B) and 13 Zambian (subtype C) subjects using an
      interferon-gamma enzyme-linked immunosorbent spot assay. RESULTS: Our findings
      demonstrate a broad cross-reactivity of nearly 70% among all the seven Gag
      immunogens evaluated. Consensus M sequences elicited similar levels of responses
      as did the consensus B, ancestral subtype B and HXB2 peptides in subtype B
      infected US patients. In subtype C-infected Zambian subjects, responses of
      similar breadth and magnitude were elicited by consensus C, consensus M and
      ancestral M peptides. CONCLUSION: Our data demonstrate that peptide pools based
      on consensus or ancestral M-based sequences can be used to evaluate Gag-specific
      responses elicited by subtype B or subtype C-based immunogens.

PMID- 16439867
TI  - Relationships between cellular immune responses and treatment outcomes with
      interferon and ribavirin in HIV/hepatitis C virus co-infection.
AB  - OBJECTIVE: To test the hypothesis that hepatitis C virus (HCV)-specific
      interferon (IFN)gamma immune responses are correlated with HCV virological
      response following treatment in subjects with HIV-1 and HCV co-infection. DESIGN:
      Immune responses were studied in a treatment trial comparing standard interferon
      alfa (IFN) to pegylated interferon alfa (PEG-IFN), each with ribavirin (R).
      METHODS: Using HCV antigens core, NS3 and NS5, and Candida, enzyme-linked
      immunosorbent spots on peripheral blood mononuclear cells measured IFNgamma and
      interleukin (IL)-10 production. Immunologic, virologic and clinical variables
      were modeled using recursive partitioning (CART) to identify factors associated
      with HCV virological response at week 24 (VR) and week 72 (SVR) in 108 patients.
      RESULTS: There were no significant differences in baseline IFNgamma immune
      responses and higher IL-10 to NS3 in subjects with VR versus non-responders.
      Subjects who had significant decreases in IL-10 responses at week 24 compared to
      baseline for NS3, NS5, or summed HCV responses were more likely to be VR. Using
      baseline immunological responses and clinical data in CART models, patients who
      were randomized to PEG-IFN/R and had high IL-10 responses to summed HCV proteins
      were more likely to be VR (73%), whereas those on IFN/R who had low IFNgamma
      responses to Candida were less likely to be VR (5%). The main correlate of SVR
      for genotype-1 subjects was maintenance of HCV-specific IFNgamma responses from
      baseline to week 72. CONCLUSIONS: In this cohort of subjects with HIV and HCV, a
      decrease in HCV-specific IL-10 responses and maintenance of IFNgamma responses
      during treatment with IFN were associated with week 24 or 72 virological
      response.

PMID- 16439869
TI  - Interruption of antiretroviral therapy blunts but does not abrogate CD4 T-cell
      responses to interleukin-2 administration in HIV infected patients.
AB  - BACKGROUND: Intermittent administration of interleukin (IL)-2 to HIV infected
      patients leads to CD4 T-cell expansions that are associated with decreased CD4 T
      cell turnover. IL-2 is under evaluation in antiretroviral therapy (ART)
      interruption studies, but it is unclear how the emergence of viremia may affect
      CD4 expansions. METHODS: CD4 T-cell responses were evaluated in 27 HIV infected
      patients on long-term intermittent IL-2 therapy who underwent ART interruption
      immediately after an IL-2 cycle ('IL-2/off') and compared with responses from a
      previous IL-2 cycle while on continuous ART ('IL-2/on'). Immunophenotypic
      analysis, including intracellular Ki67 staining, of cryopreserved peripheral
      blood mononuclear cells was performed. RESULTS: CD4 T-cell increases, in naive
      and central memory CD4 T-cell subsets, were observed in the IL-2/on (106 and 327
      cells/microl, respectively) and IL-2/off (84 and 184 cells/microl, respectively)
      cycles 1 month following IL-2 administration. These increases were greater during
      the IL-2/on cycle (P = 0.05, P = 0.01, respectively). In both cycles, the change
      in CD4 T-cell count correlated with the change in CD4/CD25 T cells. In the IL
      2/off cycle, the change in the proportion of CD4 T cells expressing Ki67 was
      associated with both the changes in viral load (r = 0.64, P = 0.001) and the
      changes in CD4 T cells (r = -0.56, P = 0.01). CONCLUSIONS: IL-2 administration
      followed by ART interruption led to significant, although blunted, CD4 T-cell
      increases. IL-2 induced CD4 T-cell increases in the setting of emergent viremia
      were associated with decreased CD4 T-cell activation that counteracted the
      viremia-induced increases in CD4 T-cell activation.

PMID- 16439870
TI  - Disease progression in patients with virological suppression in response to HAART
      is associated with the degree of immunological response.
AB  - OBJECTIVE: To determine if immunological response is associated with disease
      progression in patients with virological suppression after initiating HAART.
      DESIGN: A cohort study of 1084 treatment-naive participants in the British
      Columbia HIV/AIDS Drug Treatment Program who had achieved viral loads < 500
      copies/ml at 3-9 months after initiating triple-drug therapy. METHODS: Cox
      proportional hazards was used to model the association with disease progression
      of baseline variables, change in CD4 cell counts and CD4 cell count strata at 6
      months. Logistic regression analysis was used to examine associations with two
      definitions of poor immunological response. RESULTS: Patients were followed for a
      median of 51.4 months. In univariate analyses, increases in CD4 cell counts of <
      25 cells/microl and absolute CD4 cell counts of < 200 cells/microl were
      associated with an increased risk of death or new AIDS events. Two mulitivariate
      models, one including baseline CD4 cell count and change in CD4 cell count from
      baseline and the other including only absolute CD4 cell counts at 6 months, were
      found to predict disease progression in this setting. Increases in CD4 cell count
      of < 25 cells/microl were associated with increasing age and inversely associated
      with low baseline CD4 cell counts, high baseline viral loads and good adherence
      to therapy. CD4 cell counts of < 200 cells/microl at 6 months were associated
      with low baseline CD4 cell counts and having AIDS at baseline. CONCLUSION:
      Patients with virological suppression are still at risk for HIV disease
      progression if adequate immunological responses are not achieved.

PMID- 16439871
TI  - GB virus C and HIV-1 RNA load in single virus and co-infected West African
      individuals.
AB  - BACKGROUND: Investigations on the impact of GB virus C (GBV-C) co-infection on
      HIV disease progression relied essentially on clinical follow-up but not on
      virologic parameters. OBJECTIVES: To detect and quantify GBV-C RNA in West
      African populations co-infected or not with HIV-1 and to correlate the RNA load
      of HIV-1 and GBV-C in co-replicating patients with different clinical conditions.
      METHODS: Three Ghanaian populations (blood donors, pregnant women and HIV
      infected patients) were subdivided into six groups according to HIV-1 and
      clinical status and GBV-C and HIV-1 RNA load was tested by quantitative real time
      reverse transcriptase-polymerase chain reaction. In one population with HIV-1
      disease, CD4+ cell count was also measured. RESULTS: Prevalence of GBV-C markers
      in HIV-1-infected groups and HIV-1 non-infected pregnant women were significantly
      higher than in healthy blood donors. Similar levels and distribution of GBV-C RNA
      load were found in each population irrespective of HIV-1 status except for a
      lower GBV-C RNA load in AIDS patients. There was a significant shift of HIV-1
      load towards lower value when GBV-C RNA was present and a trend towards an
      inverse correlation between HIV-1 and GBV-C RNA load. A positive correlation
      between CD4+ cell count and GBV-C RNA load in symptomatic HIV-1-infected patients
      was observed. CONCLUSIONS: The moderate impact of GBV-C on HIV-1 viremia is
      unlikely to entirely account for a favourable clinical outcome of replicating co
      infections.

PMID- 16439872
TI  - Altered hepatic expression of SREBP-1 and PPARgamma is associated with liver
      injury in insulin-resistant lipodystrophic HIV-infected patients.
AB  - BACKGROUND: HIV-infected patients with HAART-related lipodystrophy are frequently
      insulin resistant and at risk of non-alcoholic fatty liver disease (NAFLD) with
      steatohepatitis (NASH). The transcription factors, peroxisome proliferator
      activated receptors (PPARalpha, PPARgamma1/PPARgamma2) and sterol regulatory
      element binding proteins (SREBP-1) regulate liver lipid metabolism. Here, we
      examined whether their expression was modified and related to liver injury in HIV
      infected patients. METHODS: Fourteen HAART-treated HIV patients (nine with and
      five without insulin resistance) who had liver biopsy because of unexplained
      elevated transaminases were compared with nine non-HIV age-and body mass index
      matched patients with NAFLD and 10 controls without steatosis. Hepatic expression
      of PPARs and SREBP-1 was assessed by real time reverse transcriptase-polymerase
      chain reaction. RESULTS: Liver histology showed NASH in six of nine insulin
      resistant lipodystrophic and two of five non-insulin-resistant HIV patients.
      Compared with NAFLD or control subjects, expression of SREBP-1 was significantly
      higher only in HIV-insulin-resistant patients (P = 0.04 and P = 0.02) whereas,
      compared to controls, HIV-insulin-resistant, HIV-non-insulin-resistant and NAFLD
      patients had lower expressions of PPARgamma1 (P = 0.03, P = 0.05 and P = 0.01)
      and PPARgamma2 (P = 0.04, P = 0.05 and P = 0.01). Among HIV patients, the
      percentage of steatosis was positively correlated with SREBP-1 expression (r =
      0.62, P = 0.04) whereas the score of fibrosis was inversely correlated with
      PPARgamma1 and PPARgamma2 expression (r = -0.57, P = 0.03 and r = -0.6, P = 0.02,
      respectively). CONCLUSION: Insulin-resistant lipodystrophic HIV-infected patients
      may develop NASH. Steatosis is associated with overexpression of SREBP-1 and
      fibrosis with decreased expression of PPARgamma1 and PPARgamma2. These results
      suggest that altered expression of SREBP-1 and PPARgamma could contribute to the
      pathogenesis of steatosis and fibronecrotic changes in insulin-resistant
      lipodystrophic patients.

PMID- 16439873
TI  - Pharmacokinetics, pharmacodynamics and safety of once-daily versus twice-daily
      dosing with enfuvirtide in HIV-infected subjects.
AB  - OBJECTIVE: To investigate the pharmacokinetics, safety/tolerability and antiviral
      activity of enfuvirtide administered once-daily (QD) versus twice-daily (BID).
      DESIGN: An open-label, randomized, multiple dose, two-period crossover study
      comparing 180 mg enfuvirtide, two injections QD versus 90 mg enfuvirtide, two
      injections, BID. METHODS: Steady-state intensive pharmacokinetic samples were
      obtained on days 7 and 14. RESULTS: Thirty-seven subjects received at least one
      dose of enfuvirtide. Thirty-three subjects completed both dosing periods. The
      regimens were bioequivalent based on the ratio of geometric mean area under the
      curve (AUC)0-tau [112 +/- 6.2 microg x h/ml QD; 115 +/- 6.4 microg x h/ml 2 x
      BID; QD/BID 0.98; 90% confidence interval (CI) 0.89,1.07]. The maximum observed
      plasma concentration within a dosing interval (Cmax) was 49% higher for QD (9.5
      +/- 2.7 microg/ml) versus BID (6.3 +/- 1.7 microg/ml) and the pre-dose plasma
      concentration (Ctrough) was 57% lower for QD (1.6 +/- 1.1 microg/ml) versus BID
      (3.8 +/- 1.3 microg/ml). The LSM decrease in viral load from baseline to day 7
      was 1.0 +/- 0.14 log10 (n = 18) for QD and 1.4 +/- 0.2 log10 (n = 17) for BID
      (LSM difference 0.385; P = 0.07). Linear regression analysis suggested that
      decline in viral load up to day 7 was associated with Ctrough but not Cmax or
      AUC. There were no significant differences in adverse events between the two
      dosing regimens. CONCLUSIONS: Administration of enfuvirtide 180 mg QD results in
      bioequivalence compared with 90 mg BID based on AUC with a similar short-term
      safety profile, but a trend towards a weaker antiretroviral effect. Larger and
      longer-term studies are needed to determine if 180 mg once daily is an effective
      dosing alternative for enfuvirtide.

PMID- 16439874
TI  - Sustained control of viremia following therapeutic immunization in chronically
      HIV-1-infected individuals.
AB  - OBJECTIVE: Viral rebounds inevitably follow interruption of antiretroviral
      treatment in HIV-1-infected individuals. The randomized ANRS 093 aimed at
      investigating whether a therapeutic immunization was effective in containing the
      long-term viral replication following discontinuation of antiretroviral drugs in
      patients. METHODS: Seventy HIV-1-infected patients effectively treated with
      antiretroviral drugs were randomized to continue treatment alone or in
      combination with four boosts of ALVAC 1433 and HIV-LIPO-6T vaccines followed by
      three cycles of subcutaneous interleukin-2. The impact of vaccination on viral
      replication was assessed by interrupting antiretroviral drugs first at week 40
      and thereafter during follow-up until week 100. Antiretroviral drugs were re
      initiated according to predefined criteria. RESULTS: The median cumulative time
      (days) off treatment was greater in the vaccine group (177) than in the control
      group (89) (P = 0.01). The proportion of time (mean, SE) without antivirals per
      patient was 42.8% (5.1) and 26.5% (4.2) in the vaccine and control groups,
      respectively (P = 0.005). Viremia (median log10 copies/ml), 4 weeks following the
      first, second and third treatment interruption was higher in control patients
      (4.81, 4.44, 4.53) in comparison with vaccinated patients (4.48, 4.00, 3.66) (P =
      0.42, 0.015 and 0.024, respectively). HIV-specific CD4 and CD8 T-cell responses
      elicited by the therapeutic immunization strongly correlated with the reduction
      of the time of antiviral therapy (P = 0.0027 and 0.016, respectively).
      CONCLUSION: Our findings provide evidence that therapeutic immunization
      significantly impacts on HIV-1 replication. This translated into a decrease of up
      to 40% in the duration of exposure to antiretroviral drugs over 15 months of
      patients' follow-up.

PMID- 16439875
TI  - Multidrug-resistant tuberculosis at an HIV testing center in Haiti.
AB  - OBJECTIVE: Tuberculosis is the major opportunistic infection of HIV/AIDS in
      developing countries. We investigated the prevalence rate of multidrug-resistant
      (MDR) tuberculosis at an HIV voluntary counseling and testing (VCT) center in
      Port-au-Prince, Haiti. DESIGN AND METHODS: A cross-sectional prevalence study of
      MDR-tuberculosis was conducted at a VCT Center. All patients reporting at least 5
      days of cough were screened for tuberculosis, including sputum culture. All
      Mycobacteria tuberculosis isolates underwent drug susceptibility testing.
      RESULTS: Between January 2000 and December 2002, isolates from 330 patients
      underwent drug susceptibility testing. MDR-tuberculosis was documented in 16 (6%)
      of 281 patients with primary tuberculosis and 10 (20%) of 49 patients with
      recurrent tuberculosis. In patients with primary disease, 11 (10%) of 115 HIV
      infected patients had MDR-tuberculosis compared with five (3%) of 166 HIV
      negative patients, (risk ratio 3.2; 95% confidence interval 1.1-8.9; P = 0.0331).
      CONCLUSION: Multidrug resistance was prevalent among patients found to have
      pulmonary tuberculosis at an HIV testing center in Port-au-Prince. Patients with
      primary pulmonary tuberculosis who were HIV-co-infected were more likely to have
      multidrug resistance than HIV-negative patients. Assiduous attention to
      tuberculosis infection control measures at HIV testing centers in developing
      countries is critical to prevent nosocomial MDR-tuberculosis transmission.
      Measures may include appropriate ventilation, outdoor seating, ultra-violet
      lights, and rapid on-site screening for tuberculosis.

PMID- 16439876
TI  - Major role of hepatitis B genotypes in liver fibrosis during coinfection with
      HIV.
AB  - BACKGROUND: Little is know about the determinants of liver fibrosis progression
      and genomic variability in hepatitis B virus (HBV) in HIV/HBV-coinfected
      patients. METHODS: A cross-sectional analysis examined common characteristics of
      HBV infection in an ongoing cohort study of 308 patients with both HIV-1-positive
      Western blot and plasma HBV surface antigen (HBsAg) seropositivity. Risk factors
      for liver fibrosis were studied in a subset of 104 patients for whom liver biopsy
      and complete HBV genomic analysis were available. Analysis was performed by exact
      multiple regression analysis. RESULTS: Mean age of the study population was 40.3
      years, with a ratio male to female of 5.3 and a mean duration of HIV infection of
      9.3 years. In the subset of 104 patients, plasma HBV e antigen (HBeAg) in HBV
      replicative patients could not be detected in 28.4% and lamivudine-resistant
      mutants were detected in 67.8%. HBV genotype A was the most frequent genotype
      (73/104) and 25 patients were infected by the usually rare genotype G. METAVIR
      fibrosis score was rated F2-F4 in 70 patients. After adjustment for the most
      common known determinants of liver fibrosis, HBV genotype G [odds ratio (OR),
      12.60; 95% confidence interval (CI), 1.72-infinite; P < 0.009], efavirenz
      exposure (OR, 3.55; 95% CI, 1.14-12.14; P < 0.03), and the duration of HIV
      infection (3.86; 95% CI, 1.27-12.64; P < 0.01) were strongly associated with the
      risk of grade F2-F4 fibrosis. CONCLUSION: HBV genotype G is a determinant of
      liver fibrosis in HIV/HBV-coinfected patients and HBV genotyping should be
      considered as part of the management of patients with multiple risk factors for
      rapid progression of liver fibrosis.

PMID- 16439877
TI  - Mode of delivery and postpartum HIV-1 disease progression: the Women and Infants
      Transmission Study.
AB  - OBJECTIVE: To assess the relationship between mode of delivery and subsequent
      maternal HIV-1 disease progression. DESIGN AND METHODS: Changes in CD4+
      lymphocyte percentage (CD4%) and plasma HIV-1 RNA concentration (HIV RNA), and
      time to progression to AIDS or death among HIV-1-infected women were compared
      according to mode of delivery [cesarean section before labor and ruptured
      membranes (SCS), cesarean section after labor and/or after ruptured membranes
      (NSCS), and vaginal delivery]. Generalized estimating equations were used to
      compare changes in adjusted mean CD4% and HIV RNA counts by mode of delivery. Cox
      proportional hazard models were used to assess differences in time to AIDS or
      death. RESULTS: In adjusted analyses, there were no clinically important
      differences in HIV-1 disease progression according to mode of delivery (SCS, n =
      183; NSCS, n = 221; vaginal, n = 1087), as assessed by changes in CD4% and HIV
      RNA during the 18 months following delivery, and by progression to AIDS or death
      during a mean postpartum follow-up of 2.66 years. CONCLUSIONS: The present
      results suggest that, among HIV-1-infected women in North America, mode of
      delivery is not associated with subsequent HIV-1 disease progression.

PMID- 16439878
TI  - Invasive pneumococcal disease in a cohort of HIV-infected adults: incidence and
      risk factors, 1990-2003.
AB  - OBJECTIVE: To investigate the association between the introduction of HAART and
      invasive pneumococcal disease (IPD) in HIV-infected patients. METHODS: Incidence
      of IPD was determined from 1990 to 2003 in a cohort of HIV-infected individuals
      and a nested case-control study assessed risk factors of IPD. RESULTS: There were
      72 cases over 19,020 person-years of follow-up (overall IPD rate, 379/100,000
      person-years). In the calendar periods 1990-1995, 1995-1998, and 1998-2003, the
      IPD incidence per 100,000 person-years was 279 [95% confidence interval (CI), 150
      519], 377 (95% CI, 227-625) and 410 (95% CI, 308-545), respectively (P = 0.516).
      CD4 cell count < 200 cells/microl [odds ratio (OR), 3.0; 95% CI, 1.2-7.6), HIV
      RNA > 50,000 copies/ml (OR, 2.8; 95% CI, 1.2-6.5), hepatitis C (OR, 4.9; 95% CI,
      1.7-14.9), serum albumin (OR, 0.1; 95% CI, 0.04-0.5), injection drug use in women
      (OR, 3.8; 95% CI, 1.6-8.8), and education beyond high school (OR, 0.2; 95% CI,
      0.05-0.8) were significantly associated with IPD in multivariate analysis. No
      treatment factor, including HAART (OR, 0.7; 95% CI, 0.3-1.5) and pneumococcal
      vaccination (OR, 0.9; 95% CI, 0.5-1.6), was associated with IPD. CONCLUSIONS: IPD
      incidence did not change significantly during the widespread dissemination of
      HAART in this cohort. IPD risk was associated with several sociodemographic and
      clinical factors.

PMID- 16439879
TI  - Impact of HAART and injection drug use on life expectancy of two HIV-positive
      cohorts in British Columbia.
AB  - BACKGROUND: The introduction of HAART has led to consistent improvements in
      survival among HIV-infected individuals. However, there is evidence that not all
      populations have benefited equally from HAART and that mortality rates are higher
      in HIV-infected injection drug users than in non-users. OBJECTIVE: To model life
      expectancies for HIV-positive individuals subdivided according to history of
      injection drug use and treatment with HAART. DESIGN: Population-based study of
      HIV-positive persons in British Columbia's HIV/AIDS treatment program. METHODS:
      The primary outcome measures in this study were life expectancy at exact age 20
      and potential years of life lost. RESULTS: The highest life expectancy (38.9
      years) and lowest potential years of life lost were measured for individuals
      taking HAART and without a history of injection drug use. The lowest life
      expectancy (19.1 years) and highest potential years of life lost were measured in
      HIV-positive injection drug users who were not taking HAART. CONCLUSIONS: There
      are substantial disparities in life expectancy for persons living with HIV in
      British Columbia. Members of the injection drug community, particularly those who
      are not taking HAART, experience elevated mortality in comparison with those
      without a history of drug use.

PMID- 16439880
TI  - Confronting chronic hepatitis B virus infection in HIV: new diagnostic tools and
      more weapons.

PMID- 16439881
TI  - Long-term statin use does not act on the temporal trend of CD4 cell count in
      patients on virologically effective HAART.
AB  - Pleiotropic features are attributed to statins and fibrates, and effects on
      laboratory markers of HIV disease progression have been claimed. To assess
      whether statins/fibrates have long-term effects on the immune recovery of
      patients on virologically effective HAART, a prospective, comparative study was
      conducted on 267 dyslipidemic patients treated with either statins, fibrates, or
      on a dietary exercise programme only. Quarterly assessment of CD4 cell counts
      showed no differences between groups, thus excluding in-vivo negative
      immunological effects during effective HAART.

PMID- 16439882
TI  - Hyperglycosylated ferritin in sera of HIV-1-infected patients treated with highly
      active antiretroviral therapy.
AB  - A study was conducted to determine the relationship between ferritin and
      glycosylated isoforms of ferritin and insulin resistance in 69 HIV-infected men
      receiving HAART. Ferritin levels were significantly correlated with aspartate
      aminotransferase, alanine aminotransferase, bilirubin and with insulin
      resistance. The ferritin isoelectric focusing patterns of five insulin-resistant
      HIV-infected patients under HAART showed large amounts of hyperglycosylated
      isoforms, which was not found in 56 control subjects and 46 untreated HIV-1
      infected patients.

PMID- 16439883
TI  - CD4 cell recovery in treated HIV-2-infected adults is lower than expected:
      results from the French ANRS CO5 HIV-2 cohort.
AB  - In 61 antiretroviral-naive HIV-2-infected patients starting triple therapy at a
      median CD4 cell count of 136 cells/microl, the median increase was 41
      cells/microl at month 12, which was no different among those on protease
      inhibitors or triple nucleoside analogues. Despite virological response, as the
      median plasma load was under the detectable threshold from month 3, CD4 cell
      recovery remained poor in treated HIV-2 infection. Our results raise the question
      of the optimal regimen to recommend in HIV-2-infected patients.

PMID- 16439884
TI  - Identification of a novel HLA B*57 restricted cytotoxic T-lymphocyte epitope
      within HIV-1 rev.
AB  - HLA-B5701 and its related allele B5703 have been shown to be strongly associated
      with slow HIV-1 disease progression. To elucidate the effect of these alleles
      fully on disease progression it is essential to identify key HIV-1 epitopes that
      are restricted by these alleles. Here we describe the identification of a novel
      HLA-B5701, B5703 restricted epitope within HIV-1 rev, which accounted for up to
      25 and 40% of the total cytotoxic T-lymphocyte responses in two patients.

PMID- 16439885
TI  - Considerations about the value of sonography for the measurement of regional body
      fat.

PMID- 16439886
TI  - Graves disease: an increasingly recognized immune reconstitution syndrome.

PMID- 16439887
TI  - Inflammatory progressive multifocal leukoencephalopathy after antiretroviral
      treatment.

PMID- 16439888
TI  - First-line use of enfuvirtide-containing HAART regimen with dramatic clinical and
      immunological improvement in three cases.

PMID- 16439889
TI  - 'Tuberculosis' after commencing antiretroviral therapy in HIV patients from
      countries where Mycobacterium tuberculosis infection is common.

PMID- 16439890
TI  - Merkel cell carcinoma in an HIV-1-infected man.

PMID- 16439891
TI  - Impact of MCP-1-2518-G allele on the HIV-1 disease of children in the United
      States.

PMID- 16439892
TI  - Long-term follow-up after one-stage reconstruction of dislocated hips in patients
      with cerebral palsy.
AB  - Twelve consecutive patients (average age 10.6 years) with 14 dislocated hips
      underwent one-stage hip reconstruction between 1973 and 1981. The procedure
      consisted of (1) adductor myotomy and anterior obturator neurectomy, (2)
      circumferential capsulotomy, iliopsoas and external rotator tenotomies, and
      ligamentum teres and pulvinar excision, (3) shortening femoral varus derotational
      osteotomy, (4) acetabuloplasty, and (5) spica immobilization for 4 weeks. All
      patients were followed clinically and radiographically at an average of 16.7
      (range 12.4-19.5) years. No patients were lost to follow-up. Long-term results
      revealed complete stability in 13 of 14 hips, with no redislocations or
      subluxations. The one patient with "instability" had undergone bilateral proximal
      femoral resections for severe arthritis 12 years after left hip reconstruction;
      at the time of resection, the left hip was stable and reduced. Pain was absent in
      13 of 14 hips. There were no problems with perineal care, decubitus formation, or
      sitting tolerance. Extension and abduction improved an average of 23 degrees and
      10 degrees, respectively. Two patients' ambulatory status improved; none
      deteriorated. The mean center-edge angle was 35 degrees (range 22-50 degrees),
      and the mean migration percentage was 10.6% (range 0-31%). Complications included
      one case of degenerative arthritis, one case of painless coxa vara, and three
      episodes of supracondylar femur fractures. None of these patients developed
      radiographic evidence of avascular necrosis. In the authors' experience, one
      stage hip reconstruction consisting of soft tissue lengthening, open reduction,
      femoral osteotomy, and pericapsular acetabuloplasty results in a painless,
      mobile, and stable hip at long-term follow-up that greatly improves the patient's
      quality of life.

PMID- 16439893
TI  - Total hip arthroplasty in children with juvenile chronic arthritis: long-term
      results.
AB  - From 1984 to 2002, 20 total hip arthroplasties in children with juvenile chronic
      arthritis were performed in the authors' department. All patients had
      polyarticular disease. Average age of patients was 15.8 (range 13-24) years.
      Early onset of the disease occurred at an average age of 7.3 (4-10) years. In six
      patients the physes were open at the time of surgery. All patients had complete
      loss of joint space and various combinations of subchondral sclerosis, flattening
      of the femoral head, and anterior inclination of the neck. All patients used
      crutches for walking and joint function was very restricted. All patients were
      operated on under general anesthesia. One of them was supported additionally with
      laryngeal mask because of cervical spine involvement. No intra- or postoperative
      complications occurred. Mobilization of the patients started immediately after
      surgery, followed by a special rehabilitation program. Follow-up examination was
      based on the Merle d'Aubigne et Postel scale as modified by Charnley. Patients
      were followed at 6 weeks and 3 months after surgery and thereafter every 6 months
      with clinical and radiologic examination. Average follow-up was 9.2 (2-20) years.
      All patients had no pain and full functional ability. Although total hip
      arthroplasty is technically difficult in this age, it should be performed in
      specialized centers because pain relief, decreased deformity, and improved
      quality of life can be achieved in most patients. The only disadvantage is wear
      of the prosthesis.

PMID- 16439894
TI  - Evaluation of bone density in children with slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis (SCFE) is a condition seen during the
      preadolescent growth spurt, often in obese children and in children with
      endocrine disorders. Given that endocrine factors also play a role in bone
      density, a link between low bone mineral density (BMD) and SCFE was proposed.
      Dual energy X-ray absorptiometry (DXA) scanning of the spine and hips was
      performed on 12 children with SCFE and on 5 overweight children without this hip
      disorder. All scans were performed by the same technician using a Hologic Delphi
      W densitometer and were interpreted by a pediatric orthopedic surgeon certified
      in clinical densitometry. Z-scores were obtained using a pediatric database. Mean
      and standard deviation of the Z-scores were calculated, and paired t tests were
      used to assess differences between these subjects and the expected norm. The SCFE
      patients' Z-scores at each of the skeletal sites assessed (spine, femoral neck,
      and total hip) were greater than the mean by an average of 1 standard deviation.
      The control subjects' BMD was also greater than the mean. The P values were less
      then 0.05. These results suggest that children with SCFE do not have low BMD, but
      show bone density significantly greater then expected for age and sex. Although
      BMD is endocrinologically driven and endocrinologic abnormalities are implicated
      in SCFE, there appears to be no correlation between low BMD and SCFE.

PMID- 16439895
TI  - Residual dysplasia after successful Pavlik harness treatment: early ultrasound
      predictors.
AB  - The purpose of this study was to evaluate a group of children treated with Pavlik
      harness for developmental dysplasia of the hip (DDH) to determine early
      ultrasound characteristics that predict poor acetabular development after walking
      age. From a group of 487 infants with DDH, 55 met inclusion criteria of (1)
      ultrasound documentation of major neonatal hip instability, (2) treatment with
      Pavlik harness, and (3) a minimum of 4 years of follow-up. These 55 infants had
      100 abnormal hips. Harness treatment alone was successful in treating 87 of 100
      hips. Persistent or late acetabular dysplasia was defined from serial
      radiographs. At a mean follow-up of 5.3 years, 5 of the 87 (6%) were found to
      have sequelae (late acetabular dysplasia, avascular necrosis of the femoral head,
      or both). Three sonographic findings present on the initial ultrasound predicted
      late sequelae: (1) dynamic coverage index of 22% or less, (2) alpha angle less
      than 43 degrees, and (3) abnormal echogenicity of the cartilaginous roof on
      initial ultrasound. Abnormal echogenicity was the most specific single predictor
      of residual dysplasia (sensitivity 100% and specificity 88%). The structurally
      normal cartilaginous roof is non-echogenic except for a short triangular fibrous
      tip (the labrum). Pathologic cartilage becomes echogenic beyond the tip as
      hyaline cartilage becomes fibrous and deformed. In unstable hips that respond
      well to Pavlik harness treatment, it would appear that midterm acetabular
      development can be affected when early transformation of roof cartilage
      accompanies displacement and instability.

PMID- 16439896
TI  - High prevalence of coxa vara in patients with severe osteogenesis imperfecta.
AB  - The purpose of this study was to determine the incidence and clinical
      presentation of coxa vara in 283 patients with osteogenesis imperfecta (OI). The
      charts and X-rays of 150 girls and 133 boys with OI were reviewed. The patients
      were classified according to the Sillence classification modified by Glorieux: 94
      type I, 90 type IV, 67 type III, 18 type V, 10 type VI, and 4 type VII. The mean
      age was 9.4 years (range 0.3-23.3). Twenty-nine patients (10.2%) had coxa vara
      (23 left and 20 right). Fifty-five percent of them were type III, 24% type IV,
      13.8% type VI, and 3.4% each of types V and VII. The incidence of coxa vara was
      6% in type V, 8% in type IV, 24% in type III, 25% in type VII, and 40% in type VI
      (P < 0.001 for difference between types I, III, and IV). The mean neck-shaft
      angle was 99 degrees (range 80-110 degrees), the average head-shaft angle was 104
      degrees (range 90-120 degrees), and the mean Hilgenreiner-epiphyseal angle was 68
      degrees (range 40-90 degrees). Twenty-five patients (36 hips) had previous
      femoral rodding before diagnosis and seven hips (all type III) had no history of
      rodding. Abduction and internal rotation of the hip joints were restricted in all
      patients with this deformity. All children with coxa vara had a Trendelenburg
      gait. In conclusion, coxa vara in OI is not rare, especially in severe forms of
      the disease. Regular clinical and radiologic follow-up is indicated in children
      with previous femoral rodding and in severely affected children, particularly
      those with OI type III.

PMID- 16439897
TI  - Hand injuries in children: a prospective study.
AB  - The purpose of this prospective clinical study was to identify the true
      incidence, pattern, and location of the injury and nature of fracture after hand
      injuries in different pediatric age groups attending a hand unit. Three hundred
      sixty children (237 boys, 123 girls) under 16 years of age who presented with
      hand injuries between April 1, 2000, and Sept. 30, 2000, were included in the
      study. Bony injuries accounted for 65.5% (236 injuries); 33.3% (120 injuries)
      were soft tissue injuries. The projected annual incidence rate for skeletal
      injuries was 418/100,000 children. The incidence was low in toddlers
      (34/100,000), more than doubled in preschool children (73/100,000), and steeply
      increased to around 20-fold after the 10th year (663/100,000). Girls had a higher
      incidence of hand injuries among toddlers and preschool children. Crushing was
      the most common cause of hand injury (64%), and most injuries were sustained at
      home (45%). Toddlers sustained soft tissue injuries predominantly (86%) and older
      children sustained more bony injuries (77%). Sport was the cause of injures
      commonly in the older children. There was a higher incidence of fracture in the
      little finger (52%) followed by the thumb (23%). The proximal phalanx was the
      most frequently fractured bone (67%) among the phalanges. Diaphyseal fractures
      (46%) were more common in the metacarpals, and basal fractures (51%) were common
      in the phalanges. At discharge more than 80% of the patients felt that they were
      cured or significantly better. This paper highlights the changing pattern and the
      different varieties of hand injuries in different pediatric age groups.

PMID- 16439898
TI  - Hand trauma in shop class.
AB  - The environment and equipment used in shop class are potential sources of serious
      injury. There has been little published to date on injuries sustained in shop
      class, with no reports examining injuries to the hand. The authors report a case
      series collected from a health records database at a pediatric and hand surgery
      referral center. Fifteen patients who sustained injuries to their wrist or hand
      in shop class were identified. Sixty percent of the injuries were caused by table
      saws. Eighty percent required treatment from a hand surgeon. Sixty-seven percent
      of patients sustained a serious injury in the form of amputation or tendon or
      neurovascular injury. Most of the patients had functional deficits at final
      follow-up. Shop class is a setting where serious hand trauma can occur. School
      administrators and educators should direct efforts at preventing these injuries.
      Parents and students must recognize the risks associated with shop class.
      Physicians should be prepared for severe injuries and the frequent need for hand
      surgical consultation.

PMID- 16439899
TI  - Pediatric olecranon fractures: open reduction and internal fixation with
      removable Kirschner wires and absorbable sutures.
AB  - The authors present an original fixation technique for pediatric olecranon
      fractures that avoids reoperation to remove hardware as compared with the
      standard fixation technique with Kirschner wires and tension band wiring as
      advocated by the AO technique. The authors' technique uses two percutaneously
      placed Kirschner wires to fixate displaced transverse and oblique olecranon
      fractures. Prior to the insertion of the wires, the fracture is reduced through a
      standard open approach. Augmentation of the pin fixation is achieved with
      absorbable sutures. Six patients have been treated with this technique, with a
      mean follow-up of 13 months. No immediate complications have been noted; one
      patient has a loss of extension of 10 degrees at the elbow. Radiographic results
      are good, with no loss of reduction. This technique avoids the need for
      reoperation for hardware removal without compromising the quality of reduction.

PMID- 16439900
TI  - Development and validation of the AO pediatric comprehensive classification of
      long bone fractures by the Pediatric Expert Group of the AO Foundation in
      collaboration with AO Clinical Investigation and Documentation and the
      International Association for Pediatric Traumatology.
AB  - A series of four agreement studies (classification sessions) were conducted to
      support the development and validation of a comprehensive pediatric long bone
      fracture classification system. This system follows the principle of the Muller
      AO classification for long bones in adults and integrates most relevant existing
      pediatric classification systems. The diagnosis includes the distinction between
      epiphyseal (E), metaphyseal (M), or diaphyseal (D) fractures, as well as
      identification of child-specific features. This article describes the proposed
      system in some detail. Digital standard preoperative anteroposterior and lateral
      radiographs from 267 consecutive pediatric patients (<16 years old and open
      physis) with single fractures of the distal humerus, radius, or tibia were
      collected at a single university children's hospital. Fractures were classified
      independently by five experienced pediatric surgeons. The classification process
      was assessed for reliability using the kappa coefficient and accuracy using
      latent class modeling separately for each bone for bone type, and separately for
      each bone type for child codes. At the last classification session, kappa values
      for E-M-D and child code classifications were mostly above 0.90, and accuracy
      estimates were between 75% and 100% for different surgeons, types, and bones.
      Disagreement and misclassification of fractures were overall very low; hence,
      experienced and trained surgeons can classify pediatric long bone fractures using
      the proposed system with high accuracy based on standard radiographic views. The
      authors encourage wide consultation and further evaluation of this proposed
      pediatric long bone classification system with a larger number of future users
      with different training before being used for documentation and clinical studies.

PMID- 16439901
TI  - Proximal humerus fractures sustained during the use of restraints in adolescents.
AB  - Injuries to skeletally immature individuals sustained during restraints have been
      rarely documented. The authors report a series of five proximal humerus fractures
      in skeletally immature patients (average age 15.3 years) that occurred during
      restraint with handcuffs. A similar mechanism of injury was identified in all of
      the cases. All five injuries were Salter-Harris type I or II, and three of the
      five required operative intervention. At short-term follow-up, all patients are
      doing well without evidence of growth disturbances. To the authors' knowledge,
      this is a unique mechanism of injury that could be avoided with proper education.

PMID- 16439902
TI  - The use of conscious sedation for pain control during forearm fracture reduction
      in children: does race matter?
AB  - Recent reports in the medical literature indicate that certain racial disparities
      have been identified in healthcare. The authors sought to identify the potential
      relationship between the use of pain medications in African-American and
      Caucasian children undergoing forearm fracture reduction. This retrospective
      cohort study was performed at a university-affiliated tertiary care children's
      hospital emergency department. All Caucasian and African-American patients who
      underwent a closed reduction of a fractured ulna or radius over the 2-year
      observational period were enrolled. Patients were excluded from the study if they
      were admitted to the hospital for an open reduction or had multiple injuries. The
      relationship between race, gender, insurance status, time of admission, length of
      stay in the emergency department, fracture characteristics, and the use of
      conscious sedation was analyzed. t tests, chi-square tests, and stepwise logistic
      regression were used for data analysis. A total of 503 patients were included,
      83% Caucasian and 17% African-American. Four hundred four patients received
      conscious sedation as part of their fracture reduction procedure and 99 did not.
      Univariate analysis showed that African-American and Caucasian children had
      different forearm fracture patterns (P = 0.0116) and different severities of
      angulation (P = 0.0094). Multivariate statistical analysis revealed that higher
      amounts of fracture translation (P < 0.0001) and angulation (P < 0.0027) and
      younger age of the patient (P = 0.0059) were significant predictors of conscious
      sedation use. Race was not found to be significantly associated with the use of
      conscious sedation (P = 0.0606 in univariate analysis, P = 0.1678 in multivariate
      analysis). The authors found that the decision to use conscious sedation for
      pediatric forearm fractures was not influenced by race, but was influenced by
      certain fracture characteristics and patient age.

PMID- 16439903
TI  - Use of the elbow compass universal hinge in pediatric patients.
AB  - The purpose of this study was to review the Compass Universal Hinge dynamic elbow
      external fixator in pediatric conditions. Eight patients with diagnoses of ulnar
      club hand (n = 2), proximal radial synostosis with hypoplastic coronoid (n = 1),
      pterygium cubitale (n = 2), and elbow arthrofibrosis (n = 3) were identified.
      Indications for fixator placement were to maintain elbow stability during forearm
      lengthening (two cases), protect a coronoid reconstruction (one case), increase
      range of motion via the fixator (two cases), and maintain stability and increase
      range of motion after open release (three cases). There were five boys and three
      girls with an average age at surgery of 11.5 (range 3-19) years. In each case,
      the goal for fixator use was achieved: both forearm lengthenings were completed
      without elbow instability, the coronoid reconstruction healed in good position,
      and four of five patients obtained increased range of motion via the fixator
      (average improved arc of motion of 31 degrees), with all elbows remaining reduced
      and stable. Complications included four pin tract infections, one of which became
      osteomyelitis; two broken/loose pins; and two cases of decreased elbow range of
      motion. Average follow-up was 29 (range 3-62) months. Use of the Compass
      Universal Hinge dynamic external fixator can be adapted to children and has
      proven useful in managing certain difficult conditions.

PMID- 16439904
TI  - Dome osteotomy for posttraumatic cubitus varus: a surgical technique to avoid
      lateral condylar prominence.
AB  - The indication for surgery in most children with posttraumatic cubitus varus is
      the presence of an unsightly deformity. The function of the limb is generally not
      impaired. Lateral closing-wedge supracondylar osteotomy, although a widely used
      corrective procedure, tends to produce lateral condylar prominence, thus
      jeopardizing the cosmetic outcome. The authors used the dome supracondylar
      osteotomy, as described by Tien et al, as the corrective procedure for cubitus
      varus in 12 consecutive children. The average follow-up was 2.3 (range 1-4)
      years. The objective evaluation was done by one of the authors by measuring the
      pre- and postoperative lateral condylar prominence index, carrying angle, and the
      range of movement at the elbow. The patients and parents were also asked to self
      assess the cosmetic outcome. There were seven excellent and five good results.
      None of the children showed a prominent lateral humeral condyle. Hypertrophic
      scar formation and ulnar neurapraxia were seen in one patient each. These results
      were comparable to the published results of lateral closing-wedge osteotomy in
      terms of correction of carrying angle and preservation of elbow motion and were
      superior to those of the lateral closing-wedge osteotomy in terms of the
      prominence of lateral humeral condyle, acceptability of the scar, and cosmesis.
      The authors offer independent verification of the observation that the technique
      of dome osteotomy as described by Tien et al for the correction of the
      posttraumatic cubitus varus is a simple, safe, and technically sound procedure
      that prevents the lateral condyle from becoming prominent and yields an excellent
      cosmetic outcome.

PMID- 16439905
TI  - Percutaneous trigger thumb release in children.
AB  - The objective of this study was to determine whether percutaneous release of the
      A1 pulley is an adequate treatment of trigger thumb in children. Twenty-three
      children under the age of 6 years with 27 trigger thumbs fixed in flexion were
      evaluated prospectively. All were treated with a percutaneous release of the A1
      pulley in an ambulatory setting and followed for at least 1 year. Interphalangeal
      and metacarpophalangeal joint range of motion, pinch strength, static two-point
      discrimination sensibility, and triggering were examined and compared with the
      unaffected thumb at the end of follow-up. After a mean follow-up of 3 years, 25
      of the thumbs had an excellent result without residual triggering. Two of these
      thumbs had mild metacarpophalangeal extension deficit 1 month after surgery that
      resolved completely with specific exercises. One thumb relapsed and required
      subsequent open release and was considered a poor result. One child was lost to
      follow-up. There were no sensibility defects, strength loss, interphalangeal
      motion loss, or metacarpophalangeal hyperextension deformities. Percutaneous
      release of the A1 pulley is an effective and safe option in the treatment of
      trigger thumb in children.

PMID- 16439906
TI  - Chronic recurrent anterior sternoclavicular joint instability: results of
      surgical management.
AB  - Chronic anterior sternoclavicular joint (SCJ) instability may cause pain and
      persistent functional limitation in active patients. Although SCJ reconstruction
      and medial clavicular resection have been advocated in these situations, the
      results of surgical treatment are not well characterized. The purpose of this
      investigation was to determine the functional outcome of surgical treatment in
      adolescent and young adult patients with chronic recurrent anterior SCJ
      instability. Fifteen patients with chronic recurrent anterior SCJ instability
      refractory to nonoperative therapy who underwent joint reconstruction or medial
      clavicular resection were evaluated for pain and function using the American
      Shoulder and Elbow Surgeons (ASES) Standard Shoulder Assessment Form and the
      Simple Shoulder Test (SST). At average follow-up of 55 months, the mean ASES
      score was 85 and the mean SST score was 10.9. Sixty percent of patients reported
      stable, pain-free joints, although 87% (n = 13) reported some limitations of
      athletic or recreational activity. There were no surgical complications, and no
      patient underwent subsequent revision procedures. Although subsequent activity
      modification is often required, surgical treatment of chronic anterior SCJ
      instability in adolescents and young adults can provide near-complete pain relief
      and return of shoulder and upper extremity function.

PMID- 16439907
TI  - Analysis of lower extremity alignment in achondroplasia: interobserver
      reliability and intraobserver reproducibility.
AB  - This study was designed to evaluate the reliability and reproducibility of
      frontal plane malalignment measurements using the mechanical axis deviation
      method in achondroplasia and to determine whether the patient's age has any
      influence on these measurements. A total of 150 anteroposterior standing
      radiographs of the lower extremities were randomly selected for the study.
      Radiographs were divided into three groups according to age: group 1, younger
      than 6 years of age; group 2, 6 to 10 years of age; group 3, older than 10 years
      of age. Interobserver agreement for the medial proximal tibial angle and the
      lateral distal tibial angle measurements were poor (0.32 and 0.38, respectively)
      in group 1, but agreement increased between observers with increasing patient
      age. Good to excellent intraobserver reproducibility was found in all groups,
      except measurement of the medial proximal tibial angle in group 1, where the
      results were poor (0.36). Significant measurement errors in the proximal and
      distal tibial joint lines are possible in children less than 6 years of age with
      achondroplasia.

PMID- 16439908
TI  - Relationship between osteochondritis dissecans of the lateral femoral condyle and
      lateral menisci types.
AB  - The purpose of this study was to examine the relationship between osteochondritis
      dissecans (OCD) of the lateral femoral condyle and lateral menisci. From 1993 to
      2002, 38 knees (28 patients) were diagnosed with OCD of the lateral femoral
      condyle. OCD locations were graded by the Cahill and Berg classification. The
      types of lateral menisci were classified by Watanabe's classification. The
      relationship between OCD of the lateral femoral condyle and lateral menisci was
      examined. On the anterior-posterior view, 25 OCDs were located in zone 4 and 13
      in zone 5. The types of lateral menisci were complete discoid in 19 knees,
      incomplete discoid in 15, and normal in 4. Ten of the 19 complete discoid menisci
      were damaged. Complete discoid menisci without tears were found in OCDs located
      in zone 4; incomplete discoid menisci were found in OCDs located in zone 5. The
      authors found a relationship between the type of OCD and the state of the lateral
      meniscus.

PMID- 16439909
TI  - Anterior tibial tendon transfer in relapsing congenital clubfoot: long-term
      follow-up study of two series treated with a different protocol.
AB  - Two series of patients with relapsing congenital clubfoot were treated by
      transfer of the anterior tibial tendon to the third cuneiform under the extensor
      retinaculum. The two series were reviewed at the end of skeletal growth to
      evaluate the effectiveness of the surgical procedure. The first series included
      19 clubfeet and the second 16. The two series of clubfeet were initially treated
      by two different manipulative techniques and two different complementary soft
      tissue release operations. In relapsing clubfeet, the foot dorsiflexion/eversion
      activity of the tibialis anterior was suppressed and the muscle functioned as an
      invertor. At follow-up the functional results of the second series of patients,
      in whom the relapsing deformity was passively correctable at the time of surgery,
      were better than those of the first series of patients, in whom the relapsing
      deformity was sometimes less passively correctable. None of the operated patients
      had a further relapse. In both series, the angles formed by the longitudinal axis
      of the navicular and the first cuneiform, the calcaneus and the fifth metatarsal,
      and the calcaneus and the cuboid, evaluated both by plain radiographs and by CT
      scan, were smaller than in normal feet and in the clubfeet that did not relapse.
      Transfer of the anterior tibial tendon to the third cuneiform underneath the
      extensor retinaculum corrects and stabilizes relapsing clubfeet by restoring
      their normal function of foot dorsiflexion/eversion. As a consequence, the
      cuneiforms and the cuboid were shifted more laterally than normal, as shown by
      both x-rays and CT scan.

PMID- 16439910
TI  - Histologic and histochemical analysis of muscle specimens in idiopathic talipes
      equinovarus.
AB  - Congenital idiopathic talipes equinovarus is a relatively common disorder of
      uncertain etiology with a wide variance of clinical severity. Many theories have
      been postulated over the years without universal agreement in regard to the cause
      of this disorder. These hypotheses include vascular, viral, genetic, anatomic,
      compartment syndrome, environmental, and positioning considerations. A great deal
      of recent discussion has focused on a neuromuscular etiology for this condition.
      Muscle biopsies from the gastrocnemius, abductor hallucis, flexor digitorum
      longus, flexor hallucis, and tibialis posterior were obtained during
      posteromedial surgical release for idiopathic talipes equinovarus from September
      1994 to October 2000 at the authors' institution. Ninety-five feet in 68 patients
      yielded a total of 431 muscle specimens. All of the specimens were processed and
      examined by light microscopy by an expert neuromuscular pathologist. In addition,
      95 tissue samples were further processed for histochemical studies and electron
      microscopy. Three hundred seventy-two specimens (86.3%) showed no evidence of a
      pathologic diagnosis with normal fiber-type ratios and no type I fiber grouping
      indicative of neuromuscular pathology. Only 4 specimens (0.9%) showed type I
      fiber predominance, and 55 specimens (12.8%) revealed muscle fiber atrophy. The
      results of this study do not support the theory that a neuromuscular abnormality
      may be significant in the etiology of idiopathic talipes equinovarus.

PMID- 16439911
TI  - Treatment of ankle instability in children and adolescents with a modified
      Chrisman-Snook repair: a clinical and patient-based outcome study.
AB  - Ligamentous injuries to the lateral ankle complex, although rare in the child
      with open physes, increase with age and are seen with considerable frequency in
      late childhood and adolescence. In athletic, ligamentously lax individuals,
      recurrent sprains may lead to ligament attenuation and instability. When
      instability becomes chronic and interferes with everyday activity, reconstruction
      is indicated. The literature on reconstruction addresses primarily the adult
      population, with minimal guidance in treating the child and adolescent. The
      authors report their experience with 48 reconstructions performed in patients
      aged 8 to 17 years (mean 14.5 years) over a 12-year period. Mean follow-up was
      6.5 years. All patients failed to respond to conservative treatment, including
      casting or bracing and physical therapy. All had disabling instability. All had a
      positive drawer sign clinically, and all but one had significant talar tilt on
      preoperative stress radiographs. A modification of the Chrisman-Snook procedure
      was used. Forty-four ankles in 38 patients were available for clinical and
      radiographic re-evaluation. One patient with generalized systemic ligamentous
      laxity required bilateral repair for failure of previous Evans procedures 8 years
      earlier; the remaining patients had primary repairs and remain asymptomatic. Each
      has a negative drawer sign and a reduction of talar tilt from a preoperative
      average of 14.5 degrees to a postoperative average of 4 degrees, based on stress
      radiographs. An outcomes questionnaire was administered to all patients, who
      subjectively rated their pain and instability at extremely low levels (1/10) and
      their function at a high level (8/10). All patients had their expectations met
      regarding the results of surgery. There was no radiographic evidence of
      degenerative arthritis at follow-up. The authors recommend this as an excellent
      means of treating children with chronic ankle instability who have failed to
      respond to conservative treatment. The authors have modified Chrisman's procedure
      by using a much smaller incision and improved graft isometry.

PMID- 16439912
TI  - Plantar opening-wedge osteotomy of cuneiform bones combined with selective
      plantar release and dwyer osteotomy for pes cavovarus in children.
AB  - Neurological pes cavovarus is a challenging deformity to treat during childhood.
      Based on physiopathology, we propose the following original surgical procedure.
      Plantar-opening wedge osteotomy of the three cuneiform bones, preceded by
      selective plantar release, corrects forefoot pronation which is the primum movens
      of the deformity, and corrects the cavus at its apex. A calcaneal valgisation
      closing wedge osteotomy, is indicated if pre-operative planning revealed subtalar
      joint stiffness, incompatible with secondary hind foot realignment in valgus. The
      follow-up had to be at least 5 years or to reach skeletal maturity. Twenty-six
      children (36 feet) satisfied these criteria. Mean age at surgery was 10.3 years
      old. All the children had a neurological disease which was progressive for 65% of
      them (75% of the feet). Mean follow-up was 6.9 years. This treatment was
      effective, with a mean percentage of cavus correction of 74%, reaching 100% for
      31% of the feet. Complete or partial cavus correction was still observed at last
      follow-up for 75% of the feet. At last follow-up, global result was satisfactory
      in 63.9% and non satisfactory in 36.1% of feet. Flat-foot was observed, of minor
      type, in only 2 cases. Apart from triple arthrodesis, iterative surgery relative
      to residual deformity (foot adduction, plantar sticking of the first metatarsal
      head) was indicated for 4 feet (11%). A triple arthrodesis was required in 12
      cases (33%). In conclusion, this treatment provides mid-term satisfactory
      correction of the cavus and may allow avoiding triple arthrodesis at skeletal
      maturity.

PMID- 16439913
TI  - Effectiveness of serial stretch casting for resistant or recurrent knee flexion
      contractures following hamstring lengthening in children with cerebral palsy.
AB  - A retrospective review of all cerebral palsy (CP) patients with resistant or
      recurrent knee flexion contractures treated with serial stretch casting was
      performed. The protocol consisted of sequential wedging (5 degrees per week) of
      fiberglass casts until maximum knee extension had been achieved. Measurements
      were made prior to the initiation of casting, at completion of the casting, and
      at 1 year after the casting. Forty-six subjects, with 75 involved extremities,
      met the study inclusion criteria. Mean age at the time of initiation of casting
      was 12.7 years. Using radiographic measurements, the mean initial degree of knee
      flexion contracture was -17.6 degrees. At the completion of casting, the mean
      knee flexion angle was -8.1 degrees. The mean duration of casting was 30 days. At
      1 year after completion of the casting, the mean knee flexion angle was -12.2
      degrees. Initial correction to within 10 degrees of full extension was achieved
      in 76% of extremities. Age less than 12 years and initial flexion contracture of
      less than -15 degrees were statistically significant factors related to
      maintenance of correction at 1 year. Complications included soft tissue
      compromise in 13 extremities (17%), transient neurapraxia in 9 extremities (12%),
      and tibial subluxation in 1 extremity (1%). Serial stretch casting was successful
      in correcting resistant knee flexion contractures in the majority of cases.
      Casting was less effective in teenagers and those with larger contractures.
      Complications were minimized by proper casting technique and controlled rate of
      correction.

PMID- 16439914
TI  - Intramedullary nail fixation of femoral and tibial percutaneous rotational
      osteotomy in skeletally mature adolescents with cerebral palsy.
AB  - Twenty percutaneous rotational osteotomies, stabilized with interlock nails, were
      performed in the lower limbs of 15 skeletally mature adolescents with cerebral
      palsy to correct rotational deformities. The medical records and radiographs of
      those patients were retrospectively reviewed. Nineteen osteotomies (95%) in 15
      patients healed without major complications. One patient had one tibia (5%)
      pseudarthrosis, which was successfully treated with additional fibular osteotomy
      and exchanging the nail. Excluding this case, the average healing time for the
      femoral and tibial osteotomies was 8 weeks, ranging from 7 to 9 and from 6 to 10
      weeks, respectively. Casting was not required to add stability. Percutaneous
      rotational osteotomy with intramedullary nail fixation is a reliable and
      effective treatment option to correct rotational malalignment of the lower limb
      in skeletally mature patients with cerebral palsy.

PMID- 16439915
TI  - Function and well-being in ambulatory children with cerebral palsy.
AB  - The purpose of this study was to determine whether there is a significant
      association between function and well-being in children with cerebral palsy. To
      determine this, the authors used validated measures of function (Gillette
      Functional Assessment Questionnaire, Gross Motor Function Classification System,
      Gross Motor Function Measure, and walking speed) and correlated them to health
      related quality of life (HRQOL) measures (Pediatric Outcomes Data Collection
      Instrument, Pediatric Quality of Life instrument). In a cross-sectional study of
      ambulatory children with mild to moderate cerebral palsy aged 10.2 +/- 3.2 years,
      mild to moderate decreases in function were found when compared with normative
      data. As the assessment of HRQOL comprises both functional well-being and
      psychosocial well-being, the authors decided to specify the aspect of well-being
      to which they were referring. It was found that the child's function was not
      correlated to psychosocial well-being. The children with mild cerebral palsy had
      greater effects on their psychosocial well-being than would be predicted by their
      functional disability. Functional measures were good at predicting the functional
      well-being but were weak at predicting the psychosocial arm of well-being.

PMID- 16439916
TI  - Rapid progression of scoliosis following insertion of intrathecal baclofen pump.
AB  - Placement of an intrathecal baclofen pump is a common treatment of spasticity in
      cerebral palsy patients. Though effective, the hardware is prone to malfunction,
      and multiple revisions are often necessary. Additional complications have also
      been described, including infection and drug toxicity or withdrawal. The authors
      report another complication of intrathecal baclofen therapy: accelerated
      progression of scoliosis after pump insertion. A retrospective chart review was
      performed on four patients who showed accelerated scoliotic progression after
      intrathecal baclofen pump insertion for treatment of spasticity. Cobb angles were
      measured from preoperative and postoperative radiographs to determine the rate of
      scoliotic degeneration both before and after pump insertion. Although there may
      not be a direct correlation between intrathecal baclofen and scoliosis, the
      authors consider the issue important enough to warrant discussion with any
      patient considering intrathecal baclofen.

PMID- 16439917
TI  - Orthopaedic implications of multiple gestation pregnancy with triplets.
AB  - Intrauterine crowding has been implicated as a risk factor in several orthopaedic
      conditions, such as developmental dysplasia of the hip (DDH), metatarsus
      adductus, and torticollis. The goal of this study was to see whether orthopaedic
      conditions associated with intrauterine crowding were more frequent in multiple
      gestation pregnancies, specifically in triplets. The authors reviewed their
      experience over a 10-year period with 261 children who were products of triplet
      pregnancies. They surveyed 13 orthopaedic conditions and found only one
      condition, torticollis, that had a greater incidence than that reported in single
      gestation pregnancies. A 0% incidence of DDH was found in these patients. Routine
      ultrasound screening cannot be recommended in these patients based on these
      results.

PMID- 16439918
TI  - Morbidity of iliac crest bone graft harvesting in adolescent deformity surgery.
AB  - The iliac crest as a source of bone graft has remained popular and continues to
      be the standard source of bone graft material in spinal arthrodesis surgery. The
      purpose of the present study was to quantify the frequency and severity of
      posterior iliac crest bone graft harvest site pain associated with adolescent
      spinal deformity correction procedures. Patients were evaluated prospectively at
      a minimum of 1 year after a spinal fusion procedure for idiopathic scoliosis or
      kyphosis. Patients were asked to quantify the pain level at their harvest site
      over the previous month based on a 0-to-10 numeric rating scale. Data were
      collected on 71 patients: 60 with adolescent idiopathic scoliosis and 11 with
      Scheuermann's kyphosis. There was no gender difference noted, with 1 of the 10
      boys (10%) and 6 of the 61 girls (10%) reporting postoperative pain. Seven of 60
      patients with scoliosis reported pain (12%), whereas none of the patients with
      Scheuermann's kyphosis reported pain. None reported a pain level greater than 3
      of 10 or any effect on activity level. This series shows that iliac crest bone
      graft harvest site pain is absent in most patients (90%) and of limited severity
      in those who reported pain (score <or=3), suggesting that the postoperative
      morbidity associated with autograft use is minimal in adolescent patients.

PMID- 16439919
TI  - Orthopaedic sequelae of meningococcal septicemia.
AB  - The records of 143 patients admitted with a diagnosis of meningococcal septicemia
      were reviewed to identify vascular, cutaneous, and osseous sequelae. During the
      acute phase of the disease there were 21 deaths and 17 patients lost tissue.
      Thirty-six digits were allowed to autoamputate and six surgical amputations were
      performed. Each of the latter developed physeal growth arrests proximal to the
      level of amputation. Four patients underwent fasciotomies for compartment
      syndrome. Two of these patients had absent distal pulses and at surgery were
      found to have nonviable limb segments; the authors conclude that fasciotomy is
      rarely indicated. Sixteen patients were identified with a total of 41 growth
      arrests. Twenty-three of these occurred under areas of cutaneous scarring and
      were diagnosed 2 to 9 years after the index admission. The authors believe that
      patients requiring debridement and/or skin grafting of areas of skin necrosis
      should be reviewed regularly during the growth period to identify physeal damage
      at a stage when less complex surgery may be indicated.

PMID- 16439920
TI  - An analysis of the functional health of obese children and adolescents utilizing
      the PODC instrument.
AB  - Childhood and adolescent obesity is increasing in prevalence and is known to have
      long-term medical and musculoskeletal consequences. The baseline Pediatric
      Outcomes Data Collection Instrument (PODCI) was administered to 50 obese patients
      (>95th percentile BMI for age) or their parent (for those <11 years) presenting
      to a pediatric orthopaedic clinic to assess overall function. There were no
      differences between sexes (31 boys, 19 girls) or age group (>11 years, n = 36;
      <11 years, n = 14) in any demographic or PODCI category. Compared with normative
      data, there was significant impairment in sports and pain identified in both
      genders, African-Americans, and those older than 11 years. These findings were
      consistent when comparing genders, ethnicities, and ages. There was no difference
      in happiness between any gender, age, or ethnic group. All groups reported
      essentially neutral satisfaction. There appears to be a lack of self-recognition
      of or reluctance to admit functional impairment secondary to obesity. Being
      obese, African-American ethnicity, and age older than 11 years appear to be risk
      factors for limited, yet significant, functional impairment.

PMID- 16439921
TI  - Effects of phototherapy on the growth plate in newborn rats.
AB  - The aim of the present study was to evaluate the effect of phototherapy and
      oxidative stress on the growth plate of newborn rats. Forty newborn Sprague
      Dawley rats were randomized into a phototherapy group and a control group. Twenty
      of the rats received phototherapy for 7 days. All zones of the growth plate were
      assessed with quantitative histomorphometric analysis. Individual zonal lengths
      were measured for the reserve zone (RZ), the proliferative zone (PZ), the
      hypertrophic zone (HZ), ossifying cartilage (OC), and total zone (TZ) of the
      growth plate. Levels of plasma malondialdehyde (MDA), an index of oxidative
      stress, were also evaluated. Compared with zonal lengths on day 7 after
      phototherapy between the two groups, the phototherapy group had significantly
      lower values than those of controls for RZ (5.13 +/- 0.36 vs. 6.4 +/- 0.85 mm x
      10(-2); P < 0.001), PZ (20.6 +/- 3.0 vs. 29.25 +/- 1.68 mm x 10(-2); P < 0.001),
      HZ (15.4 +/- 1.44 vs. 20.87 +/- 1.12 mm x 10(-2); P < 0.001), OC (47.08 +/- 4.25
      vs. 62.06 +/- 3.7 mm x 10(-2); P < 0.001), and TZ (88.15 +/- 6.56 vs. 118.48 +/-
      4.50 mm x 10(-2); P < 0.001). Plasma MDA levels were correlated with the size of
      the PZ in the phototherapy group (r = -0.53, P = 0.01). In a multivariate
      regression model for all rats, being in the phototherapy group was the best
      predictor of the size of the TZ (beta = -0.94, P < 0.001), with the total
      variance explained being 88%. These results suggest that in newborn rats,
      receiving phototherapy is associated with early impairment of growth plate
      structure, and oxidative stress may be the main risk factor for growth plate
      injury.

PMID- 16439922
TI  - Two questions about osteogenesis imperfecta.

PMID- 16439923
TI  - Variations in nursing practice environments: relation to staffing and hospital
      characteristics.
AB  - BACKGROUND: While improvements in nursing practice environments are considered
      essential to address the nursing shortage, relatively little is known about the
      nursing practice environments in most hospitals. OBJECTIVES: The objectives of
      this study are to describe variations in nursing practice environments across
      hospitals and to examine their associations to hospital bed size, community size,
      teaching intensity, and nurse staffing levels. METHODS: The research design was
      cross-sectional analyses of nurse survey and administrative data for 156
      Pennsylvania hospitals from 1999. For comparative reference, nurse survey data
      from earlier years from two small samples of nursing magnet hospitals were
      analyzed. The nursing practice environment was measured by the Practice
      Environment Scale of the Nursing Work Index (PES-NWI). RESULTS: Nursing practice
      environments varied greatly among the hospitals studied. The nursing practice
      environments of the small samples of magnet hospitals were superior to those of
      the Pennsylvania sample. About 17% of the hospitals in the Pennsylvania sample
      had favorable practice environments. Pennsylvania hospitals with better practice
      environments had higher RN-to-bed ratios. Practice environment differences were
      not associated with hospital bed size or community size. Hospitals with a modest
      teaching level had less favorable environments. DISCUSSION: Considerable
      variation exists in the quality of hospital nursing practice environments. Five
      out of six hospitals are targets for improvement. Favorable nursing practice
      environments can be achieved in a wide variety of hospital settings.

PMID- 16439924
TI  - Subjective fatigue, influencing variables, and consequences in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Fatigue is a common symptom of chronic obstructive pulmonary disease
      (COPD), but little is known about the specific nature of COPD-related fatigue and
      its impact on daily life. OBJECTIVES: To (a) describe characteristics of fatigue
      in people with COPD and (b) test a theoretically and empirically supported model
      of the relationships among subjective fatigue, dyspnea, functional performance,
      anxious and depressed moods, and sleep quality in people with COPD. METHODS: A
      cross-sectional descriptive study was conducted with 130 people with moderate to
      severe COPD. Measures included the following: a Numerical Rating Scale (NRS) for
      frequency, intensity, and distress of fatigue and dyspnea; Fatigue Assessment
      Instrument (FAI); Chronic Respiratory Disease Questionnaire (CRQ); Profile of
      Mood States (POMS); Pittsburgh Sleep Quality Index (PSQI); Functional Performance
      Inventory (FPI); and spirometry. Path analysis was used to examine the
      relationships among variables. RESULTS: Participants reported moderate amounts of
      fatigue, which was described as situation-specific, had considerable
      consequences, and was responsive to rest and sleep. Dyspnea was slightly greater
      than fatigue, as measured by the NRSs (p <.001), and there was a strong
      relationship between fatigue and dyspnea (r =.74, p < .001). Dyspnea, depressed
      mood, and sleep quality accounted for 42% of the variance in subjective fatigue.
      Fatigue, dyspnea, airflow obstruction, and anxious mood accounted for 36% of the
      variance in functional performance. CONCLUSIONS: Fatigue is an important problem
      that affects performance of daily activities in people with COPD. The
      relationships or interactions that exist among fatigue and other symptoms are
      complex.

PMID- 16439925
TI  - Caring Behaviors Inventory: a reduction of the 42-item instrument.
AB  - BACKGROUND: Caring traditionally has been at the center of nursing. Effectively
      measuring the process of nurse caring is vital in nursing research. A short, less
      burdensome dimensional instrument for patients' use is needed for this purpose.
      OBJECTIVES: To derive and validate a shorter Caring Behaviors Inventory (CBI)
      within the context of the 42-item CBI. METHODS: The responses to the 42-item CBI
      from 362 hospitalized patients were used to develop a short form using factor
      analysis. A test-retest reliability study was conducted by administering the
      shortened CBI to new samples of patients (n = 64) and nurses (n = 42). RESULTS:
      Factor analysis yielded a 24-item short form (CBI-24) that (a) covers the four
      major dimensions assessed by the 42-item CBI, (b) has internal consistency (alpha
      =.96) and convergent validity (r =.62) similar to the 42-item CBI, (c) reproduces
      at least 97% of the variance of the 42 items in patients and nurses, (d) provides
      statistical conclusions similar to the 42-item CBI on scoring for caring
      behaviors by patients and nurses, (e) has similar sensitivity in detecting
      between-patient difference in perceptions, (f) obtains good test-retest
      reliability (r = .88 for patients and r=.82 for nurses), and (g) confirms high
      internal consistency (alpha >.95) as a stand-alone instrument administered to the
      new samples. CONCLUSION: CBI-24 appears to be equivalent to the 42-item CBI in
      psychometric properties, validity, reliability, and scoring for caring behaviors
      among patients and nurses. These results recommend the use of CBI-24 to reduce
      response burden and research costs.

PMID- 16439926
TI  - Treatments of coronary artery disease improve quality of life in the long term.
AB  - BACKGROUND: Cardiovascular diseases are currently the most common cause of death
      worldwide. This trend has been predicted to continue until 2020. The effects of
      treatments by bypass operation or angioplasty on the long-term health-related
      quality of life (HRQoL) in patients with coronary artery disease (CAD) have not
      been adequately studied. OBJECTIVE: To measure the HRQoL and its changes during 8
      years of follow-up after a treatment intervention. METHODS: The primary study
      series consisted of 280 patients, of whom 100 underwent coronary artery bypass
      grafting (CABG), 100 had percutaneous transluminal coronary angioplasty (PTCA),
      and 80 were prescribed medication. At 1 year, 81 CABG patients, 74 PTCA patients,
      and 64 patients in the medication group responded. In the final analysis after 8
      years, 63 CABG patients, 57 PTCA patients, and 34 patients in the medication
      group remained. HRQoL surveys were conducted 1 and 8 years after the treatment
      interventions. HRQoL was measured using the Nottingham Health Profile (NHP),
      which has been tested and evaluated in Finland. RESULTS: CABG patients had a
      statistically significantly better HRQoL 8 years after the operation than at
      baseline on the dimensions of mobility (p <.001), energy (p =.003), and pain (p
      =.031). PTCA patients had a statistically significantly better HRQoL 8 years
      after the intervention on the dimensions of emotional reactions (p =.002), pain
      (p =.003), mobility (p =.004), and energy (p =.005). A significant impairment on
      the dimension of sleep had taken place during the 8 years follow-up after PTCA (p
      =.018). No significant changes were seen in the HRQoL of the patients on
      medication at either 1 or 8 years. DISCUSSION: The need for treatment and primary
      and secondary prevention of CAD will increase in the future, especially in the
      case of high-risk patients. The present findings indicate that CABG and PTCA
      continue to significantly improve CAD patients' HRQoL 8 years after the
      intervention.

PMID- 16439927
TI  - Influence of a computer intervention on the psychological status of chronically
      ill rural women: preliminary results.
AB  - BACKGROUND: Adaptation to chronic illness is a lifelong process presenting
      numerous psychological challenges. It has been shown to be influenced by
      participating in support groups. Rural women with chronic illness face additional
      burdens as access to information, healthcare resources, and sources of support
      are often limited. Developing virtual support groups and testing the effects on
      psychosocial indicators associated with adaptation to chronic illness may help
      remove barriers to adaptation. OBJECTIVE: To examine the effects of a computer
      delivered intervention on measures of psychosocial health in chronically ill
      rural women including social support, self-esteem, empowerment, self-efficacy,
      depression, loneliness, and stress. METHODS: An experimental design was used to
      test a computer-delivered intervention and examine differences in psychosocial
      health between women who participated in the intervention (n = 44) and women in a
      control group (n = 56). RESULTS: Differences between women who participated in
      the intervention and controls were found for self-esteem, F(1,98) = 5.97, p
      =.016; social support, F(1,98) = 4.43, p =.038; and empowerment, F(1,98) = 6.06,
      p =.016. A comparison of means for depression, loneliness, self-efficacy, and
      stress suggests that differences for other psychosocial variables are possible.
      DISCUSSION: The computer-based intervention tested appears to result in improved
      self-esteem, social support, and empowerment among rural women with chronic
      illness. Descriptive but nonsignificant differences were found for other
      psychosocial variables (depression, loneliness, self-efficacy, and stress); women
      who participated in the intervention appeared to improve more than women in the
      control group.

PMID- 16439928
TI  - Keepin' it R.E.A.L.!: results of a mother-adolescent HIV prevention program.
AB  - BACKGROUND: The concern that adolescents may be placing themselves at risk for
      contracting HIV has led to widespread public and parental support for HIV
      prevention programs. Several programs on increasing communication between parents
      and teenagers have been tested, but the study of the impact of these programs on
      resulting sexual behavior is lacking. OBJECTIVE: To test the efficacy of two
      interventions for mothers and their adolescents in delaying initiation of sexual
      intercourse for youth who are not sexually active and encouraging the use of
      condoms among sexually active youth. METHODS: Employed were a control group and
      two treatment groups: one based on social cognitive theory (SCT) and the other a
      life skills program (LSK) based on problem behavior theory. Assessments were
      conducted before the intervention (baseline) and at 4, 12, and 24 months after
      the baseline assessment. RESULTS: Adolescents and their mothers (total N = 582)
      enrolled in the trial. At baseline, the adolescents ranged in age 11-14 years and
      were mostly male and African American. The mean age of the mothers was 37.9
      years, and most were African American and single. The primary analyses showed no
      difference among groups in abstinence rates for adolescents. However, adolescents
      in the LSK group demonstrated an increase in the condom use rate, and those in
      the SCT and control groups scored higher on human immunodeficiency virus (HIV)
      knowledge than those in the LSK group. Mothers showed substantial increases over
      time in comfort talking about sex and self-efficacy. For HIV knowledge, mothers
      in the SCT group scored significantly higher than those in the LSK and control
      groups. CONCLUSION: The results of this study are comparable to previous studies
      that have included mothers in the HIV education of their adolescents. Although
      the program did not demonstrate a substantial effect on abstinence rates,
      increases were observed in condom use among adolescents and in mother's sex-based
      discussions and comfort in talking about sexual issues.

PMID- 16439929
TI  - Secondary prevention of intimate partner violence: a randomized controlled trial.
AB  - BACKGROUND: Despite the recognition of intimate partner violence (IPV) against
      women as a global health issue associated with significant morbidity and
      mortality, evidence-based treatment strategies for primary care settings are
      lacking. OBJECTIVE: To assess the comparative safety behaviors, use of community
      resources, and extent of violence following two levels of intervention. METHODS:
      A randomized, two-arm, clinical trial was completed in urban public primary care
      clinics with 360 abused women who assessed positive for physical or sexual abuse
      within the preceding 12 months. Two interventions were tested: a wallet-sized
      referral card and a 20-minute nurse case management protocol. Outcome measures
      were differences in the number of threats of abuse, assaults, danger risks for
      homicide, events of work harassment, safety behaviors adopted, and use of
      community resources between intervention groups over a 24-month period. RESULTS:
      Two years following treatment, both treatment groups of women reported
      significantly (p <.001) fewer threats of abuse (M = 14.5; 95% CI 12.6, 16.4),
      assaults (M = 15.5, 95% CI 13.5, 17.4), danger risks for homicide (M = 2.6; 95%
      CI 2.1, 3.0), and events of work harassment (M = 2.7; 95% CI 2.3, 3.1), but there
      were no significant differences between groups. Compared to baseline, both groups
      of women adopted significantly (p <.001) more safety behaviors by 24 months (M =
      2.0; 95% CI 1.6, 2.3); however, community resource use declined significantly (p
      <.001) for both groups (M = -0.2; 95% CI -0.4,-0.2). There were no significant
      differences between groups. DISCUSSION: Disclosure of abuse, such as what happens
      with abuse assessment, was associated with the same reduction in violence and
      increase in safety behaviors as a nurse case management intervention. Simple
      assessment for abuse and offering of referrals has the potential to interrupt and
      prevent recurrence of IPV and associated trauma.

PMID- 16439931
TI  - [Mycoses of the head and neck].
AB  - OBJECTIVES: The ever growing number of immunocompromized patients and increasing
      travel to areas where fungal diseases are endemic explain why in recent years
      mycoses have emerged as important infections in clinical practice. It is
      essential that pathologists and clinicians be knowledgeable about them. RESULTS:
      Head and neck infections are common in disseminated mycoses. The most frequent
      causative yeasts or yeast-like organisms include Candida albicans, Cryptococcus
      neoformans, Histoplasma capsulatum var capsulatum, Blastomyces dermatitidis,
      Paracoccidioides brasiliensis and Coccidioides immitis. Other causative fungal
      pathogens include Aspergillus fumigatus and less frequently, Rhizopus oryzae and
      Rhinosporidium seeberi. Since their pathophysiology is in most cases similar,
      those microorganisms share a common clinical pathological picture. Head and neck
      mycoses may simulate carcinoma or cause upper airway obstruction. Symptoms such
      as dysphonia or dysphagia associated with hyperplastic and ulcerative lesions on
      endoscopic examination should prompt biopsies. An inflammatory tissue reaction
      with pseudoepitheliomatous hyperplasia warrants caution since it may lead to a
      mistaken diagnosis of cancer. CONCLUSION: The pathologist must look carefully for
      microorganisms with special stains. Clinicians and pathologists must be aware of
      these mycoses to identify the causative agent, isolated it by culture, and
      prescribe adequate treatment for the patients.

PMID- 16439932
TI  - [Universal hearing screening: 10,835 newborns tested in maternity wards of the
      geographical Department of Eure, France].
AB  - OBJECTIVES: The aim of this study was to evaluate Universal Screening using
      transient evoked otoacoustic emisions (TEOAE) in the geographical Department of
      Eure -France. MATERIAL AND METHODS: This hearing screening was initially
      developed at a single maternity ward (September 1999 to December 2002), and then
      throughout the Department (January 2003 to December 2003). One or two successive
      TEOAE tests were recorded. In cases of a positive test, a new TEAO was recorded
      at otolaryngology consultation one month later. If this test was again positive,
      a new consultation with brainstem auditory evoked potential (BAEP) was scheduled.
      If hearing loss was suspected following BAEP, an audiometric test was performed.
      RESULTS: A total of 10,770 newborns were screened (99.38%), 65 newborns were lost
      to follow-up (0.59%), 18 bilateral hearing losses were identified (1.6/1000), and
      5 of them had hearing loss risk factors. CONCLUSION: This study demonstrated that
      a hearing screening program in the maternity ward using TEOAE is recommended and
      provides optimal results.

PMID- 16439930
TI  - Development and validation of a screen for specialized discharge planning
      services.
AB  - BACKGROUND: There is no rigorously developed and empirically validated screening
      tool to identify, early in the hospital stay, those adults who will use
      specialized hospital discharge planning services. OBJECTIVES: To develop and
      validate a screen using hospital admission clinical data that discriminates
      between adults who use and do not use specialized discharge planning services.
      METHODS: Subjects consisted of prospectively sampled adult patients admitted to
      two hospitals located in a Midwestern United States city in 1998 (tool
      development sample, n = 991) and 2002 (validation sample, n = 303). Variables
      suggestive of being predictive of use of specialized hospital discharge planning
      services were identified from the literature and were obtained from direct
      participant interviews, record review, and administrative databases. The outcome
      was a documented referral for involvement of specialized discharge planning
      personnel with the patient's plan of care and was identified from review of
      hospital records. RESULTS: Of 24 variables examined, only age, disability, living
      alone, and self-rated walking limitation were jointly predictive of use of
      specialized discharge planning services in the development sample. Standardized
      coefficients from the joint model were used to estimate a screening score. A cut
      point was derived and had a sensitivity of 75% and specificity of 78% in the
      development sample. The screen performed equally well in the validation sample
      and the development sample. CONCLUSION: A screening tool consisting of a limited
      number of characteristics readily available early in the hospital stay that were
      shown to be highly predictive of the use of specialized discharge planning
      services was developed. The application of such a tool will hopefully assist
      providers to deploy services appropriately and in a timely fashion.

PMID- 16439933
TI  - [Physiological changes in balance control of adults aged 20 to 60 years assessed
      with Equitest].
AB  - OBJECTIVES: The sense of balance depends on many factors including age. A
      considerable amount of time is spent in medical clinics attempting to identify
      potential balance problems and retrain individuals with posture and balance
      limitations. Since the past decades the development of computerized dynamic
      posturography (CDP) provided the clinicians a tool to objectively assess balance
      disorders. The aim of this study was to evaluate physiological changes in balance
      control of adults aged from 20 to 60 years. MATERIAL AND METHODS: 108 healthy
      adults volunteers were involved in the study. The Equitest CDP was used to record
      equilibrium pattern in four age groups: "a" 20-30 years old, "b" 3040 years old,
      "c" 40-50 years old and "d" 50-60 years old. RESULTS: Equilibrium patterns worsen
      progressively with age in the studied age groups, especially vestibular pattern,
      whereas visual dependence increases. CONCLUSION: Ours results show that: 1-
      presbyvestibulia takes place progressively with age. 2- between 20 and 60 years
      old, normative data should be established by decade age steps. 3- From a
      preventive point of view raises the question if this evolution is uneluctable or
      could be counteracted by physical training or adapted treatment.

PMID- 16439935
TI  - [Efficacy of Derinox assessed with one PNIF (Peak Nasal Inspiratory Flow) in
      patients suffering from common cold].
AB  - OBJECTIVES: The aim of this study was to compare the efficacy and tolerance of
      Derinox (D) to Rhinofluimucil (R) and placebo (P) in the treatment of common
      cold, using an objective measure of nasal obstruction, the Peak Nasal Inspiratory
      Flow (PNIF--Clement Clarke International, Harlow, Angleterre). PATIENTS AND
      METHODS: This randomized, double-blind, double-dummy, parallel group study
      enrolled 354 patients (34 P, 165 D et 155 R) included by 85 general
      practitioners. The treatment duration was 5 days at usual recommended dosage
      regimens. PNIF measures were done before drug administration (T0) as well as 15
      min and 3 h after each intake. Moreover, nasal obstruction, rhinorrhea and global
      discomfort were subjectively assessed. RESULTS: The efficacy of D was superior to
      that of P and R when comparing PNIF from T0 to T3 h after the first intake. At
      T15 min, rhinorrhea was significantly improved with both active treatments and
      global discomfort was significantly improved with D only. Treatment tolerance was
      satisfactory and comparable between the 3 groups. CONCLUSION: Efficacy of
      Derinox(R) was superior to that of P and R for the improvement of the nasal
      obstruction (PNIF) between T0 and T3h (main criteria) after the first intake in
      patients suffering from common cold.

PMID- 16439934
TI  - [Reconstruction after tumor resection of the anterior skull base with an of
      abdominal fat graft].
AB  - OBJECTIVES: Reconstruction of the anterior skull base is a surgical stage as
      significant as tumor removal. The quality of the reconstruction is the primary
      determinant of postoperative mortality, morbidity. The aim of our work was to
      assess the results of a reconstruction process combining: 1) a pericranium graft
      held by biological glue to complete the dura mater; 2) an abdominal fat graft
      supported by a Silastic arch to maintain the neurological structures. PATIENTS
      AND METHODS: This was a retrospective study. 55 patients (44 men and 11 women),
      59 mean age (14 - 78), were analyzed. 45 had a malignant tumor and 10 a benign
      tumor. 35 patients were treated using a mixed approach and 18 using a trans
      frontal-sinus approach alone. Forty-three patients treated for a malignant tumor
      underwent postoperative radiotherapy. Results were analyzed according to 3
      periods: 1) immediate postoperative period (<25 days); 2) early postoperative
      period (25 days - 3 months); 3) late postoperative period (> 3 months). RESULTS:
      None of the patients were lost to follow-up. The average follow up was 84 months.
      All periods considered together, we had five (9.4%) graft infections, 6 (11.3%)
      CSF leaks and 1 (1.8%) cases of meningitis. CONCLUSION: We use a simple technique
      for reconstruction. Postoperative complications were exceptional, even after
      postoperative radiotherapy. Medium and long-term results are good and similar to
      those obtained with other processes used for reconstruction of the anterior skull
      base reconstruction.

PMID- 16439936
TI  - [Physical examination of a patient with dysosmia].

PMID- 16439937
TI  - [Cherubism: a new case with review of literature].
AB  - OBJECTIVES: To evaluate radiological characteristics of cherubism. MATERIAL AND
      METHODS: We report the case of a 7-year-old boy presented with facial deformity,
      bilateral mandibular swellings, right exophthalmia and dislocated teeth.
      Panoramic radiograph, Computed tomography scan and MR imaging were performed.
      RESULTS: Panoramic radiograph revealed multiloculated osteolysis involving the
      entire mandible and the right maxilla with dislocated teeth. Computed tomography
      scan showed multicystic expansive bony masses without cortical disruption
      occupying the mandible and right maxilla with extension to the orbital floor. On
      MR, these lesions demonstrated intermediate inhomogeneous signal intensity on T1
      and T2 weighted images with high enhancement after gadolinium administration. MRI
      was useful in identifying orbital involvement. These clinical and radiological
      findings are in favor of the diagnosis of cherubism. CONCLUSION: Cherubism is a
      rare hereditary benign lesion of the mandible that appears in childhood as
      bilateral painless swellings which progress until puberty, then spontaneously
      regress. Plain radiographs and computed tomography scan are sufficient for
      diagnosis. MR imaging is useful to study the expansion to soft tissues, in
      particular in the aggressive forms, and establish preoperative vascular
      assessment. The treatment is plastic and aims to correct the facial deformities.

PMID- 16439938
TI  - [Recommendations of the vascular surgery; vascular medicine national university
      counsel (sub-section 51-04), for university professor-hospital physician
      recruitment and for university assistant professor-hospital physician
      recruitment].

PMID- 16439939
TI  - [Antithrombotic drugs in the prevention of ischemic stroke].
AB  - Stroke prevention cannot be dissociated from cardiovascular prevention in
      general. It is based on the correction of vascular risk factors, particularly
      hypertension and tobacco smoking, and on antithrombotic drugs which tackle the
      thrombo-embolic process which is the immediate cause of the ischemic event.
      Ischemic strokes exhibit considerable etiopathogenic diversity, the underlying
      cause modifying thrombus composition. In atherothrombotic brain infarction,
      platelets play a major role and antiplatelet drugs have a benefit/risk ratio
      better than that of oral anticoagulants, with a 25% reduction in the combined
      risk of ischemic stroke, myocardial infarction and vascular death. Antiplatelet
      drugs are also used in small artery diseases of the brain although the role of
      thrombosis is unknown and no specific trial has been devoted to this variety of
      cerebrovascular disease. In emboligenic cardiac diseases, atrial fibrillation in
      particular, stasis of the dilated left atrium favors coagulation phenomena, hence
      the much better efficacy of oral anticoagulants (presently vitamin K antagonists)
      both in primary and secondary prevention with a 70% risk reduction in cerebral
      infarction, compared with only 20% for aspirin. The expected benefit of
      antithrombotic drugs must be weighed against their inherent hemorrhagic risk,
      which is greatest for oral anticoagulants, slightly less for association of
      antiplatelet drugs and even less for each antiplatelet drug given alone. The use
      of antithrombotic drugs allows a targeted prevention of cerebral infarction. It
      is based on a triple case by case evaluation: that of the cause and of the risk
      it carries, that of the benefit expected from antithrombotic drugs, and that of
      their inherent hemorrhagic risk.

PMID- 16439940
TI  - ["Isolated" thrombi of the aorta: retrospective study of 10 observations].
AB  - INTRODUCTION: Thrombi of the aorta are mostly linked to atheromatous plaques on
      the aortic wall of patients with classical risk factors for cardiovascular
      disease. The thrombus rarely appears on sound arteries and in this case is called
      "isolated". METHODS: We present a retrospective study of ten patients with
      "isolated" thrombi of the aorta treated between 1995 and 2004 at the Hospital of
      Grenoble. The following parameters were considered in this analysis: age of the
      patient when the thrombosis appeared, gender, cardiovascular risk factors,
      revealing mode of the thrombus, its anatomic location, biological and
      morphological exploration results and the treatment performed. Patients with
      atheromatous plaques on the aortic wall were excluded. RESULTS: In eight out of
      ten cases the clinical presentation of the aortic thrombus is an acute ischemia
      of a limb. In all of the cases the diagnosis was confirmed by an injected thoraco
      abdominal scan apart from one case where the primary diagnosis was made using an
      arterial echo-Doppler. The search for the thrombophilia can be considered to have
      been exhaustive in seven cases. For the search of an anti-phospholipid antibody
      syndrome this has been achieved in eight cases. Two etiologic diagnoses could be
      placed. The first one revealed during the aortic thrombosis a neoplasia of
      adenocarcinomic type without any primary identified. The second case was an
      essential thrombocythemia diagnosed one year after the thrombosis. The eight
      other cases remained "isolated" after an average 2.5 years follow-up. DISCUSSION:
      Less than one hundred cases of aortic thromboses could be identified in the
      literature. The cases developing on a sound artery are difficult to quantify and
      the word "isolated" thrombus may be sometimes used by default. The hypothesis of
      an isolated focal atheromatous plaque or of inflammatory pathologies inducing a
      thrombus can be an example. The biological and morphological explorations have to
      be exhaustive even if in most of the cases they are not sufficient for the
      diagnosis. Therapy calls for anti-coagulation but is not standardized. The
      clinical follow-up appears to be essential since pathological conditions can
      possibly develop after the event of the thrombosis. It also enables refinement of
      the actions to be taken especially regarding long-term use of anticoagulants.

PMID- 16439941
TI  - [Femoral superficial artery angioplasty: long term results, initial predictive
      factors. 101 patients].
AB  - OBJECTIVE: To evaluate immediate results, clinical improvement, long-term patency
      and predictive factors of long-term outcome after superficial femoral artery
      percutaneous angioplasty. PATIENTS AND METHODS: Restrospective monocentric study
      of 101 patients (142 lesions: 105 stenoses and 37 occlusions) technical results,
      long-term patency (19 months), and clinical improvement (27,5 months) were
      analyzed. A multifactorial analysis was performed. RESULTS: Technical success was
      obtained in 99%, complications and mortality rates were respectively 3% and 2%.
      At the end of follow-up, 55 patients were clinically improved (20 lost to follow
      up), and femoral artery remained patent in 62 patients (10 to follow-up).
      Statistical analyses revealed 8 significant predictive factors of a good outcome
      (P<0.05): female gender, non-diabetic, at least one patent artery below the knee,
      AHA classification <2, no stent, treatment of an occlusion, number of
      dilatations<3, treatment by statins for hypercholesterolemia. CONCLUSION: Femoral
      superficial artery angioplasty is usually achieved with low complication rate. We
      found eight factors predictive of long-term outcome, to keep in mind when
      indications are discussed.

PMID- 16439942
TI  - [Hypertension revealing aneurysmal renal fibrodysplasia].
AB  - A 20-year-old woman consulted for severe hypertension which revealed aneurismal
      stenosing fibrodysplasia of the renal arteries. The diagnosis was established by
      duplex Doppler which visualized tight stenosis of the distal portion of the right
      renal artery and the proximal portion of the left, associated with aneurismal
      lesions downstream from the strictures (1.8 cm on the right and 1.3 cm on the
      left). The lesions were highly suggestive of fibrodysplasia and were confirmed by
      magnetic resonance angiography. Endoluminal revascularization was undertaken
      because of the severe hypertension and the presence of arterial lesions.
      Revascularization was unsuccessful and severe hypertension persisted. Surgery was
      performed in two stages. The first procedure consisted in resection of the left
      aneurismal lesion with aortorenal internal saphene bypass. Secondarily, exclusion
      of the right aneurysm was performed with cure of the stricture by extracorporal
      renal surgery with anastomosis of the renal artery to the aorta and the renal
      vein to the vena cava. Clinical outcome was favorable. Angioscan and duplex
      Doppler controls at three and six months confirmed the anatomic success of the
      revascularization. Aneurysm of the renal artery, like renal artery stenotic
      dysplasia, is a rare but probably underestimated condition due to insufficient
      screening. This diagnosis should be entertained in hypertensive young women.
      There is risk of rupture of the aneurysm. Aneurysmal lesions can be associated
      with renal artery stenosis which usually involves a short segment of the artery,
      as in our case. Renal aneurysms should be treated when one of the following
      elements is present: aneurysm measuring more than 20 mm, progressing aneurysm,
      dissection, discovery in a patient with a renal risk (single kidney, renal
      insufficiency), desire for pregnancy, severe hypertension recently discovered in
      a young subject associated with dysplastic stenosis, isolated aneurysm associated
      with recent severe hypertension, as reported here.

PMID- 16439943
TI  - The platelet componentof hemostasis in aortic surgery.
AB  - The lack of significant changes in the count and function of platelets in aortic
      surgery without use of cardiopulmonary bypass (CPB) confirms that factors of
      extracorporeal circulation exert a remarkable adverse action on the platelet
      component of hemostasis. In operations performed under hypothermic perfusion or
      circulatory arrest, disorders of the platelet component even in case of the use
      of 2 mln. CIU trasylol (aprotinin) are most pronounced which gives rise to
      excessive postoperative blood loss in the given patient group. It may be assumed
      that the increase of the dose of trasylol up to 6 mln. CIU will allow, owing to
      its cytoprotective action, preserve as well as possible the quantitative and
      qualitative properties of platelets.

PMID- 16439944
TI  - [Modern views of diabetic angiopathy of the lower limbs (epidemiology, risk
      factor, etiopathogenesis, atherosclerosis of diabetes mellitus). Part I].
AB  - Today diabetes mellitus is one of the most important problems of modern medicine.
      This review provides an analysis of the reported data on the problem of vascular
      lesion in patients with diabetes mellitus. The authors consider the problems of
      diabetes mellitus epidemiology and the incidence of vascular pathology in
      patients with disorders of carbohydrate metabolism. Introduced the
      characteristics of the main etiopathogenetic aspects of the origination of
      diabetic angiopathies with regard to the latest studies into the given subject
      matter. Special attention is focused on the development of atherosclerotic lesion
      of lower limb arteries in the presence of diabetes mellitus. The authors review
      the most important causes of initiation and activation of the process of vessel
      wall lesion and formation of atherosclerotic plaques in diabetic patients. The
      study of risk factors of vascular pathology with delineation of the most
      substantial ones is of paramount importance for both prevention and sound
      pathogenetic treatment of the given pathology as well as for refinement of the
      results of surgical treatment of atherosclerotic occlusions associated with
      diabetes mellitus.

PMID- 16439945
TI  - [Characterization of blood flow in different forms of diabetic foot syndrome].
AB  - The lowering of the mean blood flow velocity (Vmean), pulsation index (PI),
      resistance index (RI) revealed by Doppler ultrasonography is most characteristic
      of patients with the ischemic form (IF) and mixed form (MF) of diabetic foot
      syndrome (DFS). The IF is marked by the high degree damping of the pulse wave in
      limb segments (damping factor). These changes are less significant in the MF of
      DFS and are in fact lacking in patients with the neuropathic form (NF). In
      health, the ankle brachial index (ABI) is equal to 1.0. The rise of the index up
      to 1.1-1.3 is common to patients with the NF of DFS. Occlusion and stenotic
      lesions of the arteries are associated with the index lowering to 0.7-0.8. The
      decrease of the index to 0.5 is recorded in critical ischemia. Nevertheless in
      10.3% of cases with clinically manifest ischemia, the ABI remains within normal
      which is determined by arterial wall rigidity in the presence of Menkenberg' s
      atherosclerosis. Laser Doppler flowmetry provided to patients with the IF of DFS
      revealed a decrease in the level of the basic and postischemic flow in the feet
      and legs. The maintenance of the high parameters of the micro-circulatory flow in
      patients with the NF and MF of DFS is regarded as a consequence of blood shunting
      in arteriolo-venulat anastomoses. Analysis of thermograms (Thermovision 400,
      AGEMA) has demonstrated that circulatory deterioration is associated with a
      decrease in the intensity of infrared irradiation of the legs. Patients with the
      IF and MF of DFS are characterized by the "amputation" type tomograms This stems
      from the lowering of the temperature of the distal segments in the presence of
      ischemia whereas the NF is marked by the "hot feet" symptom. In patients with the
      IF of DFS, .TcpO2 is 1.3 times lower than in those with the MF and 1.7 times
      lower in the NF of DFS (p<0.05). In the MF of DFS, the level of oxygenation is
      1.3 times lower versus patients with the NF (p<0.05), in which it does not differ
      from normal. Thus, the hemodynamic parameters in different forms of DFS are
      significantly different which is especially noticeable in the distal segments of
      the legs.

PMID- 16439946
TI  - The use of the Zontik cava filter for temporary implantation to the inferior vena
      cava.
AB  - The authors review the potential for the use of the Zontik retrievable cava
      filter (CF) for temporary implantation. In the course of their observations, the
      CF was to be received by 68 patients for the time needed for the treatment of
      floating thrombi in the inferior vena cava and its tributaries using
      thrombectomy, thrombolysis or anticoagulants. In 10 patients, the CF was
      implanted in view of the risk of pulmonary thromboembolism (PTE) during and after
      obstetric-gynecological and orthopedic operations carried out in the presence of
      deep venous thrombosis of the lower limbs. After elimination of the risk of PTE
      the CF was retrieved in 38 (48.7%) patients over the period 2 to 64 days; 4
      patients declined filter retrieval; in 3 patients, the procedure ended in
      failure. In view of the risk of PTE the CF, was left for permanent implantation
      in 33 patients. Of these, in 8 patients it was left due to embolism to the filter
      and in 8 patients due to its thrombosis. One patient developed PTE which prompted
      CF retrieval on the second day following implantation. Thirty patients were
      examined over the period 12 to 62 months after CF retrieval. No signs of PTF were
      detected, the inferior vena cava was patent. Based on their own experience the
      authors investigate the conditions required for temporary implantation of the CF
      and the indications for its use, factors providing for the minimal risk of the
      recurrence of venous thrombosis and PTF after filter retrieval, and the
      possibilities of a broader practical use of the technique. They believe that
      temporary implantation of the CF is the most prospective trend in endovascular
      prevention of PTE.

PMID- 16439947
TI  - Endovascular grafting of thoracic aortic pseudoaneurysm after operation for
      coarctation.
AB  - Presented herein is a case of successful repair of thoracic aortic aneurysm by
      endograft in a female patient 21 years after replacement of the descending aorta
      for coarctation. During scheduled examination the patient was found to have
      aneurysm of proximal anastomosis. Additional examination was followed by the
      stenting of the thoracic aorta using endograft manufactured by the "GORE" Company
      (USA). The immediate results were classified as good: aneurysm was not opacified,
      the patency of the vessels of the aortic arch was well preserved. According to
      the data of check examination carried out 5 months after operation, no graft
      dislocation was marked, aneurysm was not detectable. The given case demonstrates
      low-invasive endovascular intervention permitting the avoidance of complicated
      and traumatic open regrafting of the aorta and attainment of beneficial short-
      and long-term treatment results.

PMID- 16439948
TI  - [The assessment of medical therapy effectiveness of patients with lower limb
      chronic venous insufficiency: the results of prospective study with Ginkor Fort].
AB  - The results of prospective study on combined agent Ginkor Fort are presented. The
      study included 60 patients with variceal disease and clinical picture of chronic
      venous insufficiency (CVI), II-IV CEAP class. Besides the registration of common
      and well known subjective signs (lower limb pain, heaviness and discomfort
      feelings, night palsies and paresthesia, edema), the main outcome measures
      included the results of digital photo-plethysmography (PPG). Initial assessment
      demonstrated the decrease of both venous return time (To) and muscular-venous
      pump capacity (Vo) with the increase of CEAP class; the trend of To appeared to
      be statistically significant (p=0.0318). The treatment resulted in the regression
      of main clinical complaints according to the 6-score analog scale. PPG showed the
      rise of to from 19.5+/-4.9 s to 20.5+/-3.7 s, though this trend was statistically
      insignificant (p>0.05). Vo elevated significantly from 3.69+/-2.4% to 4.04+/-2.3%
      (p<0.05), demonstrating the grown functional capacities of leg pump. PPG with To
      and Vo analysis can be used in combination with ultrasonic examination for the
      quantitative assessment of venous outflow disturbances and accordingly, of the
      CVI severity. This method can serve as an indicator of conservative treatment
      effectiveness. Combined agent Ginkor Fort is feasible for adjunctive therapy in
      complex treatment of patients with lower limb CVI symptoms.

PMID- 16439949
TI  - [Drug therapy of chronic venous insufficiency with Venza].
AB  - An open prospective study on the use of the drug Venza for complex variceal
      disease treatment was conducted. The study included 125 patients aged from 21 to
      75. The outcome measures were: patient complaints and medical history, as well as
      Doppler ultrasound of lower limb veins, arteriovenous index (AVI) and leg
      circumference at the ankle level for the objective assessment of therapeutic
      effectiveness. Malleolar circumference decreased by average 0.8+/-0.3 cm. The
      drug therapy resulted in the regression of clinical signs (leg fatigue heaviness
      and edema, night palsies). Venza had a positive effect on all evaluated
      parameters of patient's quality of life. Its clinical effectiveness was estimated
      as "very good" and "good" in 27.5% and 57.5%, respectively. The study proved the
      Venza's effectiveness in treatment of patients with lower limb chronic venous
      insufficiency.

PMID- 16439950
TI  - [Assessment of the efficacy of surgical management of lower limb varicosity from
      the viewpoint of patients' quality of life as dependent on their psychological
      status].
AB  - Altogether 150 patients suffering from lower limb varicosity (LLV, classes 2-5
      chronic venous insufficiency /GVL/ according to the CEAP) confirmed by Color
      Duplex Imaging were examined. The patients' age varied from 21 to 64 years (mean
      38 years). There were 30 (20%) men and 120 (80%) women. The CIVIQ was used to
      assess quality of life (QL) of all patients. The individual typological
      properties of the personality were defined using the mental diagnostic test
      (MDT). Based on the physical, painful, social and psychological parameters a
      significant decrease was revealed in quality of life. The highest correlation was
      discovered between the appurtenance of the examined to a definite class of
      unidimensional typology (MDT) according to the "neurotism" factor (psychological
      asthenicity of the personality) and the positive relative postoperative dynamics
      of the painful factor of the QL (CIVIQ), of patients with LLV, clasees 2 and 3
      CVI (CEAP): r=0.729492; p<0.01. For the social factor (CIVIQ) it is the level of
      the total activity (r=0.59194; P<0.05), for the physical and psychological
      factors it is the level of introversion (the degree of social contactness of the
      personality), (r=0.553448; r=0.536933 respectively,p<0.05). This is not common to
      patients with LLV, classes 4 and 5 CVI; (CEAP).

PMID- 16439951
TI  - [A complex program for the treatment of patients with post-thrombophlebitic
      disease of the lower limbs].
AB  - The aim of the work was to improve the results of the treatment of patients
      suffering from post-thrombophlebitic disease (PTPD) of the lower limbs. An
      analysis was made of the results of examination and treatment of 800 patients,
      obtained over the recent 12 years. Wide spreading of operations carried out on
      the saphenous and communicating veins led to a decrease in the number of the long
      term positive results in the presence of valvular insufficiency of the deep
      veins. At the same time combined operations performed on all three venous systems
      according to the indications cannot provide for stable results. This circumstance
      necessitates the carrying out of preventive and anti-recurrence measures. This
      formed the basis for revision of the treatment policy and development of a
      complex program for combined surgical and conservative treatment, provided there
      are strict indications for each of them, depending on the character and the
      degree of venous insufficiency in PTPD. We have worked out our own technology for
      conservative treatment; preoperative preparation and postoperative rehabilitation
      constituted a part of the program suggested. The program for permanent
      rehabilitation includes an individual training of patients in elementary
      practices of the treatment and prevention of disease progression. According to
      the program we undertook the treatment of 343 patients; the positive results
      could be attained in 87.5% of cases as shown by the 6-year follow up.

PMID- 16439952
TI  - Surgical policy in the treatment of SAD patients with thoracic and
      thoracoabdominal aortic aneurysms.
AB  - The paper reviews an experience gained with the treatment of 30 CAD patients with
      thoracic and thoracoabdominal aortic aneurysms. They were examined and treated at
      the Department of Surgery of Aorta and Its Branches, RSCS RAMS from January 1991
      to November 2004. All the patients were provided reconstructions for thoracic and
      thoracoabdominal aortic aneurysms. In 27 of them myocardial revascularization was
      performed concurrently with aortic reconstruction. When choosing the surgical
      policy we adhered to the concept of performing one-stage operations via a single
      access. In most cases, proximal anastomoses were, during surgical treatment of
      this pathology, constructed "atypically": with the aortic arch, brachiocephalic
      trunk: and carotid artery, with the descending aorta, and mammaro-coronary bypass
      grafting was performed. On repair of aneurysms of the distal portion of the arch
      and descending aorta we accomplished an enlarged left-sided lateral thoracotomy
      or thoraco-phreno-retro-peritoneal access. It is to be noted that myocardial
      revascularization was performed twice, using the descending aorta for
      establishment of proximal anastomosis of coronary bypass. In two cases,
      revascularization was carried out by means of mammaro-coronary anastomosis. In
      one case, dual autogenous vein graft and replacement ox the descending aorta was
      performed from a transverse trans-bipleural access along the fourth intercostal
      space under extracorporeal circulation. In patients provided one-stage operation
      on the aorta and coronary-arteries, the main complication was bleeding at
      operation and in the short-term postoperative period. In staged surgical
      treatment of CAD patients with thoracic and thoracoabdominal aortic aneurysms,
      the complications arose from uncorrected coronary pathology, namely iron ischemia
      and myocardial infarction. Analysis of the results evidences that one-stage
      surgical treatment of thoracic and thoracoabdominal aortic aneurysm and CAD is an
      effective method which permits the attainment of beneficial results in 93.6% of
      patients.

PMID- 16439953
TI  - Myocardial revascularization in CAD patients with left ventricular ejection
      fraction below 35%.
AB  - The aim of the present study was to compare the short- arid long-term clinical
      results in CAD patients with an initial LV ejection fraction below 35% after
      coronary stenting and coronary artery bypass grafting (CABG). METHODS AND
      RESULTS: the study accrued 94 CAD patients with an initial LV ejection fraction
      below 35%. As dependent on the revascularization techniques performed, the
      patients were distributed into two groups. The first group comprised patients
      after intracoronary stenting. The second group included patients who had
      undergone CABG. Both groups were comparable in terms of the basic clinical
      criteria. The short-term clinical success of intervention in CS and CABG groups
      accounted for 97.6% and 97.7% respectively (p>0.05). The hospital lethality was
      significantly higher in the CABG group than in the CS group and was quoted as
      13.7% versus 2.3% (p<0.05). No significant differences in the clinical status
      were recorded among patients with the clinical success. In the long-term period,
      the three-year survival in the CS and CABG groups accounted for 73.2% and 79.1%
      respectively (p>0.05). The incidence of unfavourable clinical events (UCE) in the
      CABG group was recorded significantly less frequently than in the CS group and
      constituted 21.9% versus 39% (p<0.05). Complete "freedom" from angina and UCE in
      the CABG group was recorded significantly more often among CABG group patients
      versus the CS group: 79.1% versus 60.9% respectively (p<0.05). CONCLUSION: As
      regards the immediate clinical efficacy both methods of revascularization are not
      statistically different. However, CABG is associated with a significantly higher
      hospital lethality. In turn, in the long-term period with the three-year survival
      in the study groups being statistically comparable), the incidence of UCE is
      recorded significantly most frequently in the CS group.

PMID- 16439954
TI  - Results of myocardial revascularization by two internal thoracic arteries using a
      Y-shaped conduit.
AB  - MATERIAL AND METHODS: Between August 2002 and September 2004, 276 patients with
      coronary artery disease underwent surgical treatment using a Y-shaped conduit
      formed from two internal thoracic arteries (ITA). In 268 (97.1%) patients,
      myocardial revascularization required exclusively bi-mammary bypass grafting. In
      creation of the Y-shaped conduit in the capacity of a free transplant, the
      intercepted right ITA was connected to the left internal thoracic artery (LITA).
      In the remaining 7 (2.5%) patients, venous bypasses together with the internal
      thoracic arteries were employed: in one patient (0.36%), the radial artery was
      used. RESULTS: Three patients (1.08%) died after operation. The survival rate
      accounted for 98.4%. CONCLUSION: The use of two internal thoracic arteries for
      complete myocardial revascularization provided beneficial results in the short-
      and long-term postoperative periods.

PMID- 16439955
TI  - [Surgical management of thromboses and aneurysms of the reconstructed vessels].
AB  - This paper analyses the results of reoperations in 52 patients with thromboses
      (n=42) and aneurysms (n=10) of the reconstructed vessels. The main causes of
      their development were progression of vascular disease and suppuration of a
      surgical wound. No relationship was established between complications and the
      type of suture materials. The diagnosis of the disease was made on the basis of
      the clinical data and duplex scanning. The operation of choice for thromboses of
      aortofemoral grafts was retrograde thrombectomy with reconstruction of the distal
      anastomosis, which was performed in 24 patients. Despite the controversial data
      on the possibility of thrombectomy from vein grafts the authors could accomplish
      it in 6 of 10 patients with thromboses of the femoro-popliteal vein bypasses. It
      is emphasized that the basic component of reoperations for occlusions of the
      femoro-popliteal segment lies in the formation of a tension-release arterio
      venous fistula. In the postoperative period, rethrombosis of the reconstructed
      vessels occurred in 2 patients, arrosive bleeding in 3; limb amputation was
      performed in 3 patients, one of whom died from peritonitis.

PMID- 16439956
TI  - The treatment of patients with injury to the great arteries of the lower
      extremities.
AB  - This paper analyzes the results of the treatment of 92 patients with injury to
      the great arteries of the lower limbs, which accounted for 15.9% of the number of
      all patients with injury to the great vessels. As regards lower limb ischemia,
      the patients were distributed in the following way: 15 (16%) patients had degree
      I, 27 (29%) degree IIA and 50 (55%) had degree IIB-IIIA ischemia (according to
      the classification of acute ischemia by I. I. Zatevakhin). All casualties with
      arterial trauma of the lower limbs were operated on. In the postoperative period,
      the patients were administered conservative therapy using anticoagulants,
      spasmolytics, and antiplatelet agents. Intraarterial infusion therapy,
      detoxification techniques and HBO therapy were applied. Good and satisfactory
      results were obtained in 78 (80.5%) patients; amputations were performed in 10
      (10.8%) patients. The lethality constituted 8.7% (n=8). The authors hold that
      early hospitalization to the multi-discipline continuous medical institutions
      forms the basis for refinement of the treatment results in patients with injury
      to the great arteries of the lower limbs.

PMID- 16439957
TI  - The five-year results of reconstructive surgery for critical lower limb ischemia.
AB  - This paper analyzes the immediate and long-term (5-year), results of 251
      reconstructive operations accomplished for critical lower limb ischemia in 240
      patients (stage III chronic arterial insufficiency was present in 135 and stage
      IV in 105 patients), with introduction of the unified criteria. The outcomes were
      compared in patients who had undergone revascularization above the Poupart's
      ligament -- 149 cases (100 cases of proximal reconstruction and 49 of two-level
      reconstruction) and beneath the Poupart's ligament (102 cases) as dependent on
      the stage and character of reattachment of the limb peripheral system. The study
      of the changes in the patients' status, the shifts in hemodynamics, the
      cumulative bypass patency and limb salvage has revealed the great priority of the
      choice of two-level reconstructions in patients with multilevel occlusions in
      stage IV chronic limb arterial insufficiency.

PMID- 16439958
TI  - [A favorable outcome of surgical treatment of a patient with thrombosis of the
      renal veins and inferior vena cava].
AB  - Presented herein is a clinical case report of a patient with thrombosis of the
      inferior vena cava, renal veins, acute renal failure, and anuria. The patient was
      admitted to the hospital two days after thrombosis. Diuresis was reestablished
      after emergency operation (thrombectomy from the inferior vena cava and renal
      veins). In the postoperative period, the clinical manifestations of renal failure
      and inferior vena cava syndrome regressed slowly. After 6 months of the control
      follow up the manifestations of renal failure disappeared; insignificant edema of
      the lower limbs was well preserved.

PMID- 16439959
TI  - [Simultaneous operation for left kidney carcinoma and atherosclerotic occlusion
      of the abdominal aorta in a patient with critical lower limb ischemia].
AB  - The authors describe a case of simultaneous operation for left kidney carcinoma
      and atherosclerotic occlusion of the abdominal aorta with critical lower limb
      ischemia. The sequence and a technique of surgical intervention are presented.

PMID- 16439960
TI  - [Selected issues of pathogenesis and clinical symptomatology of chronic venous
      insufficiency].
AB  - The paper presents a brief review of existing theories concerning development and
      progression of trophic disturbances in chronic venous insufficiency (CVI). The
      interrelation of physiopathological processes during CVI at the level of micro-
      and macrocirculation is delineated, the necessity and feasibility of medical
      therapy with the last generation pharmacological agents is stressed.

PMID- 16439961
TI  - [The treatment of false iatrogenic arterial aneurysms (review of literature)].
AB  - Recently an ever growing importance has been acquired by the problem of the
      treatment of iatrogenic aneurysms of the peripheral arteries, first of all, this
      is linked with a steady growth of the number of endovascular interventions. The
      development of false post-puncture aneurysms is one of the most hazardous
      complications from such interventions. Along with traditional surgical treatment
      (reconstructive operations) much attention is paid to the use of little invasive
      treatment methods for these aneurysms, e.g. the compression modality under
      ultrasound guidance.

PMID- 16439962
TI  - Topical imiquimod treatment prevents UV-light induced loss of contact
      hypersensitivity and immune tolerance.
AB  - Imiquimod (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine) is a TLR7
      agonist that induces cytokine production in TLR7 bearing antigen-presenting cells
      (APCs), including IL-12, a cytokine that has been demonstrated to be a critical
      effector molecule for contact hypersensitivity (CHS). To test our hypothesis that
      topical applications of imiquimod may protect the skin immune system against the
      deleterious effects of UV light exposures, we treated animals with this agent, or
      its vehicle or nothing before UV exposures. Although topical imiquimod exposures
      before UV light did not prevent the depletion of epidermal Langerhans cells, it
      did prevent the loss of CHS. IL-12 was important in the protective role of
      imiquimod in preventing UV-induced loss of CHS, as systemic treatment of mice
      with an anti-IL-12 p70 monoclonal antibody blocked the protective effects of
      imiquimod. Additionally, only imiquimod-treated mice were resistant to hapten
      specific tolerance induction after UV irradiation at the site of the initial
      sensitization with the hapten 2,4 dinitro-1-fluorobenzene. To model for the
      effects of TLR7 activation on the UV effect on antigen-APCs, XS52 cell line was
      used to study this interaction in an in vitro model system. This cell line
      expressed mRNA for TLR7, downregulated IkappaB, phosphorylated c-Jun N-terminal
      kinase, and secreted cytokines after exposure to imiquimod or lipopolysaccharide.
      Activation of the TLR7 signaling pathway on XS52 before UV-light exposures
      enhanced IL-12p70 secretion by this cell line. Similarly, activation of TLR7 on
      XS52 before UV-light exposure also prevented the UV-induced loss of IFN-gamma
      triggering in T cells during an allogeneic mixed lymphocyte reaction. Imiquimod
      treated, UV-irradiated XS52 triggered a more vigorous IFN-gamma production than
      did either imiquimod-treated XS52 or UV-irradiated XS52, again suggesting a
      synergy between the two treatments. Lastly, enriched lymph node CD11c+ APCs from
      mice treated with UV irradiation, imiquimod alone or the combination of UV
      irradiation and imiquimod indicated the same in vivo synergy between imiquimod
      irradiation and UV irradiation in enhancing IL-12p70 production. These data
      suggest that topical imiquimod applications may play a role in preventing UV
      induced impairment of the skin immune system, which is thought to be one of the
      critical events that allow the development of UV-induced skin cancers.

PMID- 16439963
TI  - Molecular epidemiology of hereditary epidermolysis bullosa in a Middle Eastern
      population.
AB  - Epidermolysis bullosa (EB) encompasses a large group of inherited blistering skin
      disorders caused by mutations in at least 10 genes. Numerous studies, mainly
      performed in European and US families with EB, have revealed a number of
      characteristic epidemiological and genetic features, which form the basis for
      current diagnostic and counseling strategies. However, little is currently known
      about the molecular epidemiology of EB in Middle East populations. In the present
      study, we assessed 55 EB families for pathogenic sequence alterations in the 10
      genes known to be associated with EB. Our results show unique EB subtype
      distribution and patterns of inheritance in our cohort. We also failed to detect
      recurrent mutations frequently encountered in Europe and the US, and did not
      consistently observe genotype-phenotype correlations formerly established in
      Western populations. Thus, the molecular epidemiology of EB in the Middle East is
      significantly different from that previously delineated in Europe and the US. Our
      data raise the possibility that similar differences may also be found in other
      genetically heterogeneous groups of disorders, and indicate the need for
      population-specific diagnostic and management approaches.

PMID- 16439964
TI  - Structure-function relation of efomycines, a family of small-molecule inhibitors
      of selectin functions.
AB  - Selectin-mediated leukocyte adhesion to endothelia, the crucial first step
      initiating the pathogenic cascade of inflammation, is an attractive target for
      specific therapies. The small-molecule macrolide, efomycine M, inhibits selectin
      mediated leukocyte adhesion in vitro and in vivo, and effectively alleviates
      inflammatory disorders in vivo. To define the molecular basis of the
      therapeutically relevant antiadhesive properties of efomycines, several new
      species of this family were purified and/or synthesized. Efomycines E and G were
      isolated from Steptomyces BS1261. Efomycine O was synthesized by Lewis acid
      catalyzed acetalization and efomycine M was generated by base-catalyzed
      deglycosylation. Efomycine S resulted from ester cleavage of the macrolide ring
      system, and efomycine T represents the peracetylated form of efomycine M. When
      the functional activity of efomycines on adhesion of leukocytes to vascular
      endothelium was studied, some remarkable differences between the compounds became
      apparent, inasmuch as efomycines E, G, M, and O significantly inhibited adhesion
      of both human and porcine leukocytes to the vascular endothelium, whereas
      efomycines S and T did not show any biological activity. A novel docking engine
      (ProPose), generating an improved, fully configurable protein-ligand interaction
      model, demonstrated that biological activities of efomycines can be predicted in
      silico, thus highlighting the utility of such combinatorial approaches.

PMID- 16439965
TI  - Three severe cases of EBS Dowling-Meara caused by missense and frameshift
      mutations in the keratin 14 gene.
AB  - We report three unrelated patients affected at birth with an unusually severe
      form of epidermolysis bullosa simplex Dowling-Meara type (EBS-DM) because of
      mutations in KRT14 encoding keratin 14. Two patients were heterozygous for the
      previously described p.M119T mutation. The third patient was heterozygous for a
      novel c.1246delC mutation predicting the replacement of the helix termination
      peptide and the tail domain by a 25 amino-acid aberrant carboxyterminal sequence.
      At age 2 years, patients carrying the p.M119T mutation still suffered from severe
      EBS-DM, whereas the patient harboring the c.1246delC mutation has improved over
      time. These cases illustrate genotype-phenotype correlations and have
      implications for genetic counselling of EBS.

PMID- 16439966
TI  - Perifollicular and perivascular mouse skin mast cells express corticotropin
      releasing hormone receptor.

PMID- 16439967
TI  - Mutation S233L in the 1B domain of keratin 1 causes epidermolytic palmoplantar
      keratoderma with "tonotubular" keratin.
AB  - Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant
      genodermatosis characterized by epidermolytic hyperkeratosis restricted to the
      palm and sole epidermis. The disorder is normally associated with dominant
      negative mutations in the keratin 9 (K9) gene; however, a small number of cases
      have been reported where causative mutations were identified in the K1 gene.
      Here, we present two unrelated Dutch EPPK families with striking ultrastructural
      findings: tubular keratin structures in the cytoplasm of suprabasal cells.
      Similar structures were reported previously in a German EPPK family and were
      termed "tonotubular" keratin. After excluding the involvement of the K9 gene by
      complete sequencing, we identified a novel mutation, S233L, at the beginning of
      the 1B domain of K1 in both families. Protein expression studies in cultured
      cells indicated pathogenicity of this mutation. This is the first report of a
      genetic defect in this domain of K1. The unusual gain-of-function mutation points
      to a subtle role of the 1B domain in mediating filament-filament interactions
      with regular periodicity.

PMID- 16439968
TI  - Tumor necrosis factor-alpha gene polymorphism associated with increased
      susceptibility to venous leg ulceration.

PMID- 16439969
TI  - Delayed wound healing and epidermal hyperproliferation in mice lacking JunB in
      the skin.
AB  - The cutaneous response to injury and stress comprises a temporary change in the
      balance between epidermal proliferation and differentiation as well as an
      activation of the immune system. Soluble factors play an important role in the
      regulation of these complex processes by coordinating the intercellular
      communication between keratinocytes, fibroblasts, and inflammatory cells. In this
      study, we demonstrate that JunB, a member of the activator protein-1
      transcription factor family, is an important regulator of cytokine expression and
      thus critically involved in the cutaneous response to injury and stress. Mice
      lacking JunB in the skin develop normally, indicating that JunB is neither
      required for cutaneous organogenesis, nor homeostasis. However, upon wounding and
      treatment with the phorbol ester 12-O-decanoyl-phorbol-13-acetate, JunB
      deficiency in the skin likewise resulted in pronounced epidermal
      hyperproliferation, disturbed differentiation, and prolonged inflammation.
      Furthermore, delayed tissue remodelling was observed during wound healing. These
      phenotypic skin abnormalities were associated with JunB-dependent alterations in
      expression levels and kinetics of important mediators of wound repair, such as
      granulocyte macrophage colony-stimulating factor, growth-regulated protein-1,
      macrophage inflammatory protein-2, and lipocalin-2 in both the dermal and
      epidermal compartment of the skin, and a reduced ability of wound contraction of
      mutant dermal fibroblasts in vitro.

PMID- 16439970
TI  - Environmentally responsive and reversible regulation of epidermal barrier
      function by gammadelta T cells.
AB  - The intraepithelial lymphocyte (IEL) network possibly composes the largest T-cell
      compartment in the body, but it is poorly understood. IELs show limited T-cell
      receptor (TCR) diversity and have been proposed to respond to generic stress
      signals rather than pathogen-specific antigens. Consistent with this, skin
      resident TCRgammadelta+ cells, known as dendritic epidermal T cells (DETC),
      downregulate cutaneous inflammation, promote wound healing, and protect against
      cutaneous neoplasia. These pleiotropic effects collectively suggest that DETC
      (and IEL more generally) may contribute to epithelial maintenance and barrier
      function. The present studies test this hypothesis. Using skin surface impedance
      analysis to measure hydration status and transepidermal water loss, we show that
      the epidermal barrier is defective in gammadelta T-cell deficient mice. However,
      this does not represent a constitutive role of gammadelta cells, but rather one
      that is dependent on environmental challenge, consistent with the primary role
      for lymphocytes being the response of the host to its environment. Likewise, the
      importance of the physiologic DETC-associated TCR is demonstrated by showing that
      Vgamma5+ fetal thymocytes reconstitute the barrier function defect in TCRdelta-/-
      mice, while Vgamma5-/- mice also show environmentally responsive defects in
      cutaneous physiology.

PMID- 16439972
TI  - Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene
      therapy of dystrophic epidermolysis bullosa.
AB  - Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder
      caused by mutations in the type VII collagen gene (COL7A1). Therapeutic
      introduction of COL7A1 into skin cells holds significant promise for the
      treatment of DEB. The purpose of this study was to establish an efficient
      retroviral transfer method for COL7A1 into DEB epidermal keratinocytes and dermal
      fibroblasts, and to determine which gene-transferred cells can most efficiently
      express collagen VII in the skin. We demonstrated that gene transfer using a
      combination of G protein of vesicular stomatitis virus-pseudotyped retroviral
      vector and retronectin introduced COL7A1 into keratinocytes and fibroblasts from
      a DEB patient with the lack of COL7A1 expression. Real-time polymerase chain
      reaction analysis of the normal human skin demonstrated that the quantity of
      COL7A1 expression in the epidermis was significantly higher than that in the
      dermis. Subsequently, we have produced skin grafts with the gene-transferred or
      untreated DEB keratinocytes and fibroblasts, and have transplanted them into nude
      rats. Interestingly, the series of skin graft experiments showed that the gene
      transferred fibroblasts supplied higher amount of collagen VII to the new dermal
      epidermal junction than the gene-transferred keratinocytes. An ultrastructural
      study revealed that collagen VII from gene-transferred cells formed proper
      anchoring fibrils. These results suggest that fibroblasts may be a better gene
      therapy target of DEB treatment than keratinocytes.

PMID- 16439971
TI  - Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis
      patients--an analysis of 1019 HLA-C- and HLA-B-typed patients.
AB  - A major susceptibility gene for psoriasis is located in the major
      histocompatibility complex class I region on chromosome 6 very close to the HLA
      Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis.
      The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA
      Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that
      HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years,
      P<10(-10)), higher incidence of guttate and the eruptive type of psoriasis
      (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher
      incidence of the Koebner's phenomenon (P=0.01), and more extensive disease
      (P=0.03). A striking new finding was a diverging pattern of disease severity in
      HLA-Cw*0602 positive and negative patients depending on the age of onset of the
      disease (P=0.0006). HLA-Cw*0602 positive women also had more frequent remissions
      during pregnancy (P<0.0001). All types of nail changes were, however, more common
      in the Cw*0602 negative patients (P=0.003) and they more often had multiple types
      of nail lesions (P<0.0001). The three ancestral haplotypes of Cw*0602 all
      conferred an increase in odds ratio but showed no difference in any of the
      clinical features studied. Our findings indicate that the genetic factor on
      chromosome 6 has a strong influence on the phenotype of the disease, and
      underline that differences in clinical features of psoriasis may be to a large
      extent genetically determined.

PMID- 16439973
TI  - Mutations in the desmoglein 4 gene are associated with monilethrix-like
      congenital hypotrichosis.
AB  - The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation
      in this gene has been reported in several consanguineous Pakistani families
      affected with localized autosomal recessive hypotrichosis (LAH). In addition,
      various mutations in the Dsg4 gene have been identified in animal models of
      hypotrichosis that share a characteristic phenotype called "lanceolate hair". To
      date, the features of the hair-shaft anomaly in patients with LAH have not been
      well described. We report a Japanese patient affected with congenital
      hypotrichosis that was originally diagnosed as monilethrix because she had a hair
      shaft abnormality that resembled moniliform hair. However, no mutations were
      found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations
      cause monilethrix. Instead, we identified novel compound heterozygous mutations
      in the DSG4 gene of our patient. On the maternal allele is a novel S192P
      transition within the extracellular cadherin II domain of DSG4; on the paternal
      allele is a novel 2039insT mutation leading to the generation of unstable
      transcripts. Here we present the observation that mutations in the DSG4 gene can
      cause monilethrix-like congenital hypotrichosis. Based on our findings, we
      propose that LAH and monilethrix could overlap.

PMID- 16439975
TI  - Can peer review police fraud?

PMID- 16439974
TI  - Behavioral responses of epidermal Langerhans cells in situ to local pathological
      stimuli.
AB  - Pathological stimuli provoke coordinated changes in gene expression, surface
      phenotype, and function of dendritic cells (DCs), thereby facilitating the
      induction of adaptive immune responses. This concept of DC maturation was
      established mainly by studying epidermal Langerhans cells (LCs), a prototypic
      immature DC subset at the environmental interface. Taking advantage of I-Abeta
      enhanced green fluorescent protein (EGFP) knock-in mice in which LCs can be
      visualized in intact skin, we recorded the dynamic movement of EGFP+ LCs by time
      lapse confocal microscopy. LCs exhibited a unique behavior, termed dendrite
      surveillance extension and retraction cycling habitude (dSEARCH), characterized
      by rhythmic extension and retraction of dendrites through intercellular spaces
      between keratinocytes. When monitored after skin organ culture or subcutaneous
      injection of tumor necrosis factor alpha, LCs showed amplified dSEARCH and amoeba
      like lateral migration between keratinocytes. Intravital imaging experiments
      further revealed steady-state dSEARCH motion in 5-10% of LCs. Topical application
      of a reactive hapten, DNFB, augmented dSEARCH and triggered lateral migration of
      LC in vivo. These observations introduce a new concept that in situ maturation of
      LCs is further accompanied by coordinated reprogramming of motile activities.

PMID- 16439977
TI  - Telencephalic oligodendrocytes battle it out.

PMID- 16439978
TI  - Defending the brain from estrogen.

PMID- 16439979
TI  - Indirect-pathway neurons lose their spines in Parkinson disease.

PMID- 16439980
TI  - Another BOLD role for astrocytes: coupling blood flow to neural activity.

PMID- 16439981
TI  - Directing the auditory spotlight.

PMID- 16439982
TI  - Specifying nociceptors.

PMID- 16439983
TI  - Subcellular organization of GABAergic synapses: role of ankyrins and L1 cell
      adhesion molecules.
AB  - In vertebrate nervous systems, different classes of synaptic inputs are often
      segregated into restricted compartments of target neurons. For example, distinct
      types of GABAergic interneurons preferentially innervate subcellular domains and
      have been implicated in the precise temporal regulation of integration within
      neurons and activity within networks. Recent studies suggest that the subcellular
      segregation of different classes of GABAergic synapses is largely genetically
      determined. The localization and signaling of L1 family immunoglobulin proteins
      recruited by ankyrin-based membrane adaptors might serve as compartmental labels,
      which contribute to subcellular synapse organization in cerebellar Purkinje
      neurons.

PMID- 16439986
TI  - Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas.
AB  - The recently identified claudins are dominant components of tight junctions,
      responsible for cell adhesion, polarity and paracellular permeability. Certain
      claudins have been shown to have relevance in tumor development, with some of
      them, especially claudin-4, even suggested as future therapeutic target. The aim
      of the present study was to analyze the expression of claudin-4 in the biliary
      tree, biliary tract cancers and hepatocellular carcinomas. A total of 107 cases
      were studied: 53 biliary tract cancers, 50 hepatocellular carcinomas, 10 normal
      liver and 10 normal extrahepatic biliary duct samples. Immunohistochemical
      analysis was performed on conventional specimens and on tissue microarrays as
      well. Claudin-4 was further investigated by Western blot analysis and real-time
      RT-PCR. Intense membranous immunolabeling was found for claudin-4 in all biliary
      tract cancers unrelated to the primary site of origin, namely intrahepatic,
      extrahepatic or gallbladder cancers. Normal biliary epithelium showed weak
      positivity for claudin-4. In contrast, normal hepatocytes and tumor cells of
      hepatocellular carcinomas did not express claudin-4. The results of Western
      immunoblot analysis and real-time RT-PCR were in correlation with the
      immunohistochemical findings. Cytokeratins, as CK7 (92%) and CK19 (83%) were
      mostly positive in biliary tract cancers, however, one-third of hepatocellular
      carcinomas also expressed CK7 (34%). HSA antibody (HepPar1) reacted with the
      majority of hepatocellular carcinomas (86%), while being positive in a low
      percentage of the biliary tract cancers (8%). In conclusion, this is the first
      report of a significantly increased claudin-4 expression in biliary tract
      cancers, which represents a novel feature of tumors of biliary tract origin.
      Claudin-4 expression seems to be a useful marker in differentiating biliary tract
      cancers from hepatocellular carcinomas and could well become a potential
      diagnostic tool.

PMID- 16439987
TI  - Increasing expression of serine protease matriptase in ovarian tumors: tissue
      microarray analysis of immunostaining score with clinicopathological parameters.
AB  - Matriptase is a type II transmembrane serine protease expressed by cells of
      surface epithelial origin, including epithelial ovarian tumor cells. Matriptase
      cleaves and activates proteins implicated in the progression of cancer and
      represents a potential prognostic and therapeutic target. The aim of this study
      was to examine the expression of matriptase in ovarian tumors and to assign
      clinicopathological correlations. Immunohistochemical analysis of matriptase was
      performed in tissue microarrays of 164 ovarian neoplasms including 84 serous
      adenocarcinomas, 23 mucinous adenocarcinomas, 10 endometrioid adenocarcinomas,
      six yolk sac tumors, 12 clear cell carcinomas, six dysgerminomas, eight granulosa
      cell tumors, four transitional cell carcinomas, five fibromas, and six Brenner
      tumors. All ovarian tumors except the fibromas and Brenner tumors showed
      significant expression of matriptase. The matriptase scores were significantly
      higher in the tumors than in their nontumor counterparts (304+/-26 for serous
      adenocarcinoma; 361+/-28 for mucinous adenocarcinoma; 254+/-17 for endometrioid
      adenocarcinoma; 205+/-19 for yolk sac tumor; 162+/-16 for clear cell carcinoma;
      109+/-11 for dysgerminoma; 105+/-9 for granulosa cell tumor; and 226+/-18 for
      transitional cell carcinoma). Matriptase scores in serous adenocarcinoma were
      correlated with TNM stage and FIGO stage. Our findings demonstrate for the first
      time that matriptase is overexpressed in many malignant ovarian tumors. It may be
      a novel biomarker for diagnosis and treatment of malignant ovarian tumors.

PMID- 16439988
TI  - Deciphering the pathway from the TCR to NF-kappaB.
AB  - A major regulator of lymphocyte survival and activation is the transcription
      factor nuclear factor-kappaB (NF-kappaB). Controlled activation of NF-kappaB is
      essential for the immune and inflammatory response as well as for cell
      proliferation and protection against apoptosis. The NEMO/IkappaB kinase (IKK)
      complex is the central integrator of most stimuli leading to NF-kappaB
      activation, but a detailed knowledge of the upstream events is available only for
      a limited number of stimuli. In particular, although most players have probably
      been identified, relatively little is known about the detailed molecular
      mechanisms involved in the cascade leading to NF-kappaB activation following
      engagement of the T-cell receptor by a foreign antigen. In this review, we
      discuss recent insights into this specific signal transduction cascade, and the
      way it is controlled both spatially and temporally.

PMID- 16439989
TI  - Inhibition of Cap-initiation complexes linked to a novel mechanism of eIF4G
      depletion in acute myocardial ischemia.
AB  - Translational control in the rat heart was characterized during acute myocardial
      ischemia introduced by left coronary artery ligature. Within 10 min of ischemia,
      eukaryotic (eIF)4E binds to its negative regulator, eIF4E-binding protein-1 (4E
      BP1), but the levels of 4E-BP1 are insufficient to disrupt cap-dependent mRNA
      initiation complexes. However, by 1 h of ischemia, the abundance of the cap
      initiation complex protein eIF4G is reduced by relocalization into TIAR protein
      complexes, triggering 4E-BP1 sequestration of eIF4E and disruption of cap
      dependent mRNA initiation complexes. As the heart begins to fail at 6 h,
      proteolysis of eIF4G is observed, resulting in its depletion and accompanied by
      limited destruction of 4E-BP1 and eIF4E. eIF4G proteolysis and modest loss of 4E
      BP1 are associated with caspase-3 activation and induction of cardiomyocyte
      apoptotic and necrotic death. Acute heart ischemia therefore downregulates cap
      dependent translation through eIF4E sequestration triggered by eIF4G depletion.

PMID- 16439990
TI  - Interaction of F1L with the BH3 domain of Bak is responsible for inhibiting
      vaccinia-induced apoptosis.
AB  - Apoptosis represents an important cellular defence mechanism against viral
      pathogens by virtue of its ability to remove infected cells. Consequently, many
      viruses have developed numerous strategies to prevent or delay host cell
      apoptosis in order to achieve productive replication. Here we report that
      deletion of the F1L gene from the vaccinia genome results in increased apoptosis
      during infection. We demonstrate that F1L, which has no sequence homology to Bcl
      2 family members, inhibits apoptosis at the level of mitochondria by binding to
      Bak. As a consequence, F1L prevents Bak activation, oligomerization and
      interaction with active Bax, all critical steps in the induction of apoptosis. We
      demonstrate that residues 64-84 of F1L interact directly with the Bcl-2 homology
      domain 3 (BH3) domain of Bak. This region of F1L has limited sequence similarity
      to known Bak-interacting BH3 domains. We also find that such additional BH3-like
      domains exist in the vaccinia genome. We conclude that F1L uses this specific,
      BH3-like domain to bind and inhibit Bak at the mitochondria.

PMID- 16439991
TI  - Molecular requirements for doxorubicin-mediated death in murine oocytes.
AB  - We previously published evidence that oocytes exposed to doxorubicin (DXR), a
      widely used chemotherapeutic agent, rapidly undergo morphological and biochemical
      changes via discrete effector signaling pathways consistent with the occurrence
      of apoptosis. In this report, we elucidated the molecular requirements for
      actions of this drug in oocytes. Our results indicate that within 1 h of exposure
      DXR causes rapid DNA damage, and commits the oocyte to cytoplasmic fragmentation
      by the fourth hour, followed by delayed oocyte activation and execution of
      cytoplasmic fragmentation. Inhibitors that interfere with oocyte activation
      consistently rescue cytoplasmic fragmentation, but fail to suppress DNA damage.
      There was evidence of depletion of Bax, Caspase-2, MA-3 and Bcl-x transcripts,
      suggesting that modulations by DXR caused recruitment of these maternal
      transcripts into the translation process. Furthermore, sphingolipids such as
      sphingosine-1-phosphate and ceramide modulate DXR actions by, respectively,
      altering its intracellular trafficking, or by sustaining the drug's contact with
      DNA.

PMID- 16439992
TI  - Gene therapy for malignant mesothelioma: beyond the infant years.
AB  - Mesothelioma may be particularly well suited for gene therapy treatment owing to
      its accessibility, allowing both intrapleural and intratumoral gene delivery. At
      least four gene therapy trials have been carried out in mesothelioma patients,
      using different vector systems (adenovirus, vaccinia virus, irradiated tumor
      cells), and different transgenes (herpes simplex virus thymidine kinase (HSVtk)
      combined with ganciclovir, IL-2, IFN-beta). Although small in scale, these trials
      have given an inkling of hope for therapeutic efficacy. However, it is clear that
      gene therapy protocols need to be optimized further. This paper will review
      progress made in (i) vector development, (ii) defining optimal transgenes, and
      (iii) gene delivery. Adenoviruses are the most commonly used vectors for gene
      therapy, and are continuously being improved. With respect to the nature of the
      transgenes, five categories can be distinguished: (i) 'suicide' or sensitivity
      genes (e.g., HSVtk), (ii) cytokines and other immune modulators, (iii)
      replacements for mutant tumor suppressor genes (e.g., p53), (iv) antiangiogenic
      proteins and (v) tumor antigens. It seems clear that expression of a single
      transgene is unlikely to be sufficient to eradicate a tumor, such as
      mesothelioma, that is diagnosed late in disease progression. Hence, multimodality
      therapy, including conventional therapy (chemo- and radiotherapy, surgery) with
      one or more transgenes has a higher chance of success.

PMID- 16439994
TI  - Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract
      neoplasia.
AB  - Truncation of the tumour suppressor adenomatous polyposis coli (APC)
      constitutively activates the Wnt/beta-catenin signalling pathway. This event
      constitutes the primary transforming event in sporadic colorectal cancer in
      humans. Moreover, humans or mice carrying germline truncating mutations in APC
      develop large numbers of intestinal adenomas. Here, we report that zebrafish that
      are heterozygous for a truncating APC mutation spontaneously develop intestinal,
      hepatic and pancreatic neoplasias that are highly proliferative, accumulate beta
      catenin and express Wnt target genes. Treatment with the chemical carcinogen 7,12
      dimethylbenz[a]anthracene accelerates the induction of these lesions. These
      observations establish apc-mutant zebrafish as a bona fide model for the study of
      digestive tract cancer.

PMID- 16439995
TI  - Cleavage of the siRNA passenger strand during RISC assembly in human cells.
AB  - A crucial step in the RNA interference (RNAi) pathway involves the assembly of
      RISC, the RNA-induced silencing complex. RISC initially recognizes a double
      stranded short interfering RNA (siRNA), but only one strand is finally retained
      in the functional ribonucleoprotein complex. The non-incorporated strand, or
      'passenger' strand, is removed during the assembly process and most probably
      degraded thereafter. In this report, we show that the passenger strand is cleaved
      during the course of RISC assembly following the same rules established for the
      siRNA-guided cleavage of a target RNA. Chemical modifications impairing the
      cleavage of the passenger strand also impair the cleavage of a target RNA in
      vitro as well as the silencing of a reporter gene in vivo, suggesting that
      passenger strand removal is facilitated by its cleavage during RISC assembly.
      Interestingly, target RNA cleavage can be rescued if an otherwise non-cleavable
      passenger strand shows a nick at the scissile phosphodiester bond, which further
      indicates that the cleavage event per se is not essential.

PMID- 16439996
TI  - ATM and the DNA damage response. Workshop on ataxia-telangiectasia and related
      syndromes.

PMID- 16439993
TI  - Transductional targeting of adenovirus vectors for gene therapy.
AB  - Cancer gene therapy approaches will derive considerable benefit from adenovirus
      (Ad) vectors capable of self-directed localization to neoplastic disease or
      immunomodulatory targets in vivo. The ablation of native Ad tropism coupled with
      active targeting modalities has demonstrated that innate gene delivery efficiency
      may be retained while circumventing Ad dependence on its primary cellular
      receptor, the coxsackie and Ad receptor. Herein, we describe advances in Ad
      targeting that are predicated on a fundamental understanding of vector/cell
      interplay. Further, we propose strategies by which existing paradigms, such as
      nanotechnology, may be combined with Ad vectors to form advanced delivery
      vehicles with multiple functions.

PMID- 16439997
TI  - Turnover in the Alps: an mRNA perspective. Workshops on mechanisms and regulation
      of mRNA turnover.

PMID- 16439998
TI  - cGMP signalling: from bench to bedside. Conference on cGMP generators, effectors
      and therapeutic implications.

PMID- 16439999
TI  - The functional role of Cdc6 in S-G2/M in mammalian cells.
AB  - The Cdc6 protein is required for licensing of replication origins before the
      onset of DNA replication in eukaryotic cells. Here, we examined whether Cdc6 has
      other roles in mammalian cell-cycle progression from S to G2/M phase. Using RNA
      interference, we showed that depletion of Cdc6 in synchronous G1 cells blocks G1
      to S transition, confirming the essential role of Cdc6 in the initiation of DNA
      replication. In contrast, depletion of Cdc6 in synchronous S-phase cells slowed
      DNA replication and led to mitotic lethality. The Cdc6-depleted S-phase cells
      showed fewer newly fired origins; however, established replication forks remained
      active, even during chromatin condensation. Despite such DNA replication
      abnormalities, loss of Cdc6 failed to activate Chk1 kinase. These results show
      that Cdc6 is not only required for G1 origin licensing, but is also crucial for
      proper S-phase DNA replication that is essential for DNA segregation during
      mitosis.

PMID- 16440000
TI  - Two internal ribosome entry sites mediate the translation of p53 isoforms.
AB  - The p53 tumour suppressor protein has a crucial role in cell-cycle arrest and
      apoptosis. Previous reports show that the p53 messenger RNA is translated to
      produce an amino-terminal-deleted isoform (DeltaN-p53) from an internal
      initiation codon, which acts as a dominant-negative inhibitor of full-length p53.
      Here, we show that two internal ribosome entry sites (IRESs) mediate the
      translation of both full-length and DeltaN-p53 isoforms. The IRES directing the
      translation of full-length p53 is in the 5'-untranslated region of the mRNA,
      whereas the IRES mediating the translation of DeltaN-p53 extends into the protein
      coding region. The two IRESs show distinct cell-cycle phase-dependent activity,
      with the IRES for full-length p53 being active at the G2-M transition and the
      IRES for DeltaN-p53 showing highest activity at the G1-S transition. These
      results indicate a novel translational control of p53 gene expression and
      activity.

PMID- 16440001
TI  - Granzyme A, which causes single-stranded DNA damage, targets the double-strand
      break repair protein Ku70.
AB  - Granzyme A (GzmA) induces caspase-independent cell death with morphological
      features of apoptosis. Here, we show that GzmA at nanomolar concentrations
      cleaves Ku70, a key double-strand break repair (DSBR) protein, in target cells.
      Ku70 is cut after Arg(301), disrupting Ku complex binding to DNA. Cleaving Ku70
      facilitates GzmA-mediated cell death, as silencing Ku70 by RNA interference
      increases DNA damage and cell death by GzmB cluster-deficient cytotoxic T
      lymphocytes or by GzmA and perforin, whereas Ku70 overexpression has the opposite
      effect. Ku70 has two known antiapoptotic effects-facilitating DSBR and
      sequestering bax to prevent its translocation to mitochondria. However, GzmA
      triggers single-stranded, not double-stranded, DNA damage, and GzmA-induced cell
      death does not involve bax. Therefore, Ku70 has other antiapoptotic functions in
      GzmA-induced cell death, which are blocked when GzmA proteolyses Ku70.

PMID- 16440002
TI  - RNA editing and alternative splicing: the importance of co-transcriptional
      coordination.
AB  - The carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (pol
      II) is essential for several co-transcriptional pre-messenger RNA processing
      events, including capping, 3'-end processing and splicing. We investigated the
      role of the CTD of RNA pol II in the coordination of A to I editing and splicing
      of the ADAR2 (ADAR: adenosine deaminases that act on RNA) pre-mRNA. The auto
      editing of Adar2 intron 4 by the ADAR2 adenosine deaminase is tightly coupled to
      splicing, as the modification of the dinucleotide AA to AI creates a new 3'
      splice site. Unlike other introns, the CTD is not required for efficient splicing
      of intron 4 at either the normal 3' splice site or the alternative site created
      by editing. However, the CTD is required for efficient co-transcriptional auto
      editing of ADAR2 intron 4. Our results implicate the CTD in site-selective RNA
      editing by ADAR2 and in coordination of editing with alternative splicing.

PMID- 16440003
TI  - Self-refinement of Notch activity through the transmembrane protein Crumbs:
      modulation of gamma-secretase activity.
AB  - Cell interactions mediated by Notch family receptors have been implicated in the
      specification of tissue boundaries. Tightly localized activation of Notch is
      crucial for the formation of sharp boundaries. In the Drosophila wing imaginal
      disc, the Notch receptor is expressed in all cells. However, Notch activity is
      limited to a narrow stripe of cells along the dorsal-ventral compartment
      boundary, where it induces the expression of target genes. How a widely expressed
      protein becomes tightly regulated at the dorsal-ventral boundary in the
      Drosophila wing is not completely understood. Here, we show that the
      transmembrane protein Crumbs is involved in a feedback mechanism used by Notch to
      refine its own activation domain at the Drosophila wing margin. Crumbs reduces
      the activity of the gamma-Secretase complex, which mediates the proteolytic
      intracellular processing of Notch. These results indicate a novel molecular
      mechanism of the regulation of Notch signal, and also that defects in Crumbs
      might be involved in similar abnormal gamma-Secretase complex activity observed
      in Alzheimer's disease.

PMID- 16440004
TI  - A role for fibronectin-leucine-rich transmembrane cell-surface proteins in
      homotypic cell adhesion.
AB  - The fibronectin-leucine-rich transmembrane (FLRT) family of leucine-rich repeat
      (LRR) proteins is implicated in fibroblast growth factor (FGF) signalling, early
      embryonic development and neurite outgrowth. Here, we have analysed whether FLRTs
      may also function in cell adhesion. We find that FLRT proteins can physically
      interact and that FLRT-transfected cultured cells sort out from non-transfected
      cells, suggesting a change in adhesive properties. A similar sorting effect is
      also observed in Xenopus embryos and tissue aggregates. FLRT-mediated cell
      sorting is calcium dependent and substrate independent. Deletion analysis
      indicates that cell sorting requires the LRR domains, which are dispensable for
      FLRT-mediated FGF signalling. Conversely, sorting is independent of the
      cytoplasmic domain, which is essential for FLRT-induced signalling. Therefore,
      FLRT-mediated FGF signal transduction and homotypic cell sorting can be
      molecularly uncoupled. The results indicate that FLRT proteins have a dual role,
      promoting FGF signalling and modulating homotypic cell adhesion.

PMID- 16440005
TI  - TGFBI gene mutations in Brazilian patients with corneal dystrophy.
AB  - PURPOSE: To investigate the transforming growth factor beta-induced gene (TGFBI)
      mutations in Brazilian patients with corneal dystrophy and to evaluate the
      phenotype-genotype correlation in these patients. METHODS: A total of 11
      unrelated families were studied. The diagnosis of corneal dystrophy was based on
      clinical and histopathological findings. Genomic DNA was extracted from
      peripheral blood leucocytes, and exons 4 and 12 of the TGFBIgene were amplified
      by polymerase chain reaction followed by direct sequencing on both strands.
      RESULTS: Five different mutations in the TGFBIgene were found in the probands. We
      identified the following mutations: lattice corneal dystrophy--R124C and A546T;
      Reis-Bucklers corneal dystrophy--R555Q and R124L; granular corneal dystrophy-
      R555W and Avellino dystrophy--R555W. In three of the 11 studied families there
      was no mutation in exons 4 and 12. CONCLUSIONS: This is the first report of
      mutations in the TGFBIgene in a series of Brazilian patients with corneal
      dystrophy. The findings indicate that TGFBIgene screening should be considered in
      the diagnosis of corneal dystrophy.

PMID- 16440006
TI  - Transconjunctival sutureless vitrectomy: initial experience and surgical tips.
AB  - OBJECTIVES: We report the operative details and surgical outcomes of 39
      consecutive transconjunctival sutureless vitrectomies using the TSV 25 system.
      METHODS: We retrospectively reviewed the medical records of 35 patients (39 eyes)
      who underwent surgery using TSV 25 at the Department of Ophthalmology, Waterford
      Regional Hospital between March 2003 and February 2005. Preoperative,
      intraoperative and postoperative details were recorded and analysed. We also
      performed a systematic review of our surgical technique. RESULTS: Mean (+/-SD;
      range) duration of surgery was 32.85 (17.54; 5-85) min. Methods of anaesthesia
      included retrobulbar anaesthesia (31; 79.5%) and general anaesthesia (8; 20.5%).
      The mean (+/-SD; range) length of stay was 1.53 (1.25; 0-4) days. Mean (+/-SD;
      range) visual acuities (logMAR) were -1.335 (1.15; 0.0 to -3.0) and -0.803 (1.03;
      0.1 to -3.0) preoperatively and postoperatively, respectively. The mean (+/-SD)
      intraocular pressures were 14.69 (4.64) mmHg and 11.56 (9.03) mmHg preoperatively
      and at the first dressing, respectively. Intraoperative complications included
      blockage of the TSV cutter tip during attempted clearance of organized intragel
      haemorrhage, thus requiring conversion to conventional trans pars plana
      vitrectomy (1; 2.6%). No other intraoperative complication arose. Complications
      in the postoperative period included: reactivation of dormant chorioretinal
      toxoplasmosis (1; 2.6%); postoperative posterior segment haemorrhage (3; 7.7%);
      hyphaema (1; 2.6%); transient postoperative hypotony (10; 25.6%). CONCLUSIONS:
      With appropriate case selection, and with appreciation of this technique's
      limitations, transconjunctival sutureless vitrectomy is a safe procedure.

PMID- 16440007
TI  - Early age-related maculopathy in eyes after cataract surgery.
AB  - PURPOSE: To assess age-related maculopathy (ARM) in eyes of patients who had
      undergone cataract surgery for at least a year. METHODS: Consecutive patients
      aged 60+ years who had undergone cataract surgery at Westmead Hospital, Sydney,
      Australia, during 2001-2003 were examined in 2004. Interview using standardized
      questionnaires and stereo retinal photography was performed. Retinal photographs
      were graded using the Wisconsin ARM grading system. The proportions with ARM were
      compared between surgical and nonsurgical eyes, and between this surgical cohort
      and the Blue Mountains Eye Study (BMES) population. RESULTS: Of the 622 eligible
      patients, 454 (73%) were re-examined, with a mean follow-period of 2.8 years.
      Surgical eyes had a higher proportion of early ARM compared to nonsurgical eyes
      (15.2 vs10.3%, P=0.07) and to the early ARM prevalence found in BMES participants
      of similar age (14.5 vs6.9%, P<0.01), which persisted after age standardization
      to the BMES population (9.7 vs6.9%, P<0.05). CONCLUSIONS: We found an increased
      prevalence of early ARM in surgical eyes of patients 1-3 years after cataract
      surgery. Whether this increased early ARM prevalence leads to an increased
      prevalence of late ARM in the long-term warrants further investigation.

PMID- 16440008
TI  - Do scleral flap dimensions influence reliability of intraocular pressure control
      in experimental trabeculectomy?
AB  - AIM: To compare the effect on intraocular pressure (IOP) of large vs small
      scleral flap size during trabeculectomy using adjustable sutures. METHODS:
      Trabeculectomy operations were performed on nine donor human eyes connected to a
      constant flow infusion with real-time IOP monitoring. Large scleral flaps (4 x 4
      mm, 16 mm(2), n=12) or small scleral flaps (3 x 2 mm, 6 mm(2), n=9) were
      constructed over 0.76 mm(2) sclerostomies. For each procedure, equilibrium IOP
      was measured following tight closure with two four-throw adjustable 10-0 nylon
      sutures. RESULTS: Five scleral flaps were thin or poorly constructed; four of
      these were in the initial seven procedures, implying learning effect. These had a
      mean absolute IOP of 7.6 mmHg (range 2.7-12.4 mmHg) and mean relative IOP of
      28.3% of baseline (range 10-45.8%) after closure. In the remaining 16 good
      quality procedures, mean IOP was 1.3 mmHg (range 0-3.4 mmHg) after sclerostomy,
      confirming minimal outflow resistance before closure. Following flap closure mean
      IOP was 20 mmHg (SD 4.4, range 15.5-29.3 mmHg) for large (n=8), and 18.7 mmHg (SD
      3.6, 15.9-25.8 mmHg) for small (n=8) flaps (unpaired t-test, P=0.26). Mean IOP (%
      baseline) was 71.6% (SD 8.4, range 60.6-86.6%) and 66% (SD=12.7, 46.8-86.6%) for
      large and small flap groups, respectively (unpaired t-test, P=0.2). CONCLUSIONS:
      Well-constructed scleral flaps of both sizes were able to support an average IOP
      at least two-thirds of baseline, and both had similar absolute IOP levels. Errors
      in flap construction resulted in loss of IOP control. Smaller flap size does not
      appear to compromise control of early postoperative IOP using adjustable sutures.

PMID- 16440009
TI  - The effect of artificial tear administration on visual field testing in patients
      with glaucoma and dry eye.
AB  - AIM: To examine the effects of artificial tear administration on perimetry of
      primary open-angle glaucoma patients with dry eye. METHODS: A total of 40
      patients with primary open-angle glaucoma experienced in automated perimetry with
      symptoms of dry eye were enrolled in this study. After their pretest visit, they
      were instructed to use artificial tear four times a day in both eyes for 1 week.
      After 1 week, patients had visual field testing. Test taking time, reliability
      parameters (false-positive and false-negative errors) visual field indices and
      number of depressed points at different probability levels (P<5%, P<2%, P<1%,
      P<0.5%) in both total and pattern deviation plots were compared using paired
      Ttest. RESULTS: We found significant improvement in reliability parameters (false
      positive errors from 2.4+/-2.1 to 2.1+/-1.9, P=0.02; and false-negative errors
      from 7.3+/-6.4 to 4.8+/-3.6, P=0.01) and visual field indices (MD increased from
      5.97+/-5.61 to 4.57+/-4.53, P=0.001; PSD from 4.67+/-2.95 to 4.13+/-2.77, P=0.04
      and SF decreased from 2.24+/-1.23 to 1.83+/-0.77, P=0.04) in the second testing
      after artificial tear administration. Test time significantly increased from
      11.66+/-2.55 min to 14.26+/-1.36, P=0.001. The number of depressed points at
      probability levels P<1% (P=0.03) and P<0.5% (P=0.04) at total deviation plot and
      P<2% (P=0.02) and P<0.5% (P=0.009) in pattern deviation plot decreased
      significantly. CONCLUSION: Artificial tear administration in glaucomatous
      patients with dry eye seems to improve significantly reliability parameters and
      visual field indices.

PMID- 16440010
TI  - Refractive lens exchange combined with pars plana vitrectomy to correct high
      myopia.

PMID- 16440012
TI  - Idiopathic intracranial hypertension associated with depot medroxyprogesterone.

PMID- 16440011
TI  - Relapsing reversible posterior leukoencephalopathy syndrome.

PMID- 16440013
TI  - Atypical clinical presentations of Brown-McLean syndrome.

PMID- 16440014
TI  - Functional assessment of reattached macula in nine cases with excellent Snellen
      acuities.
AB  - PURPOSE: To compare the macular functions of patients with excellent visual
      acuity after retinal detachment (RD) surgery, with the healthy fellow eye.
      METHODS: Of 214 patients, nine patients, who were successfully operated because
      of unilateral RD involving the macula and achieved excellent visual acuity, were
      analysed. The fellow eyes of the patients were taken as the control group. The
      macular functions were evaluated with visual acuity, contrast sensitivity, colour
      vision, visual field, and pattern VEP in operated and nonoperated eyes. RESULTS:
      There was no significant difference in visual acuity, contrast sensitivity,
      colour vision, and VEP outcomes between operated and nonoperated eyes. However,
      it was seen that the mean deviation in the visual field was significantly higher
      in the operated eyes (5.8+/-1.8 dB) when compared with the undetached fellow eyes
      (3.1+/-1.8 dB), (t=12.5; P=0.013). CONCLUSION: Even though the visual acuity,
      colour vision, contrast sensitivity, and VEP results returned to normal after a
      successful RD surgery, we found that the mean deviation measured by the visual
      field, which reflects the retinal sensitivity, was still significantly low after
      nearly 5 years follow-up.

PMID- 16440015
TI  - Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based
      population from South India.
AB  - PURPOSE: The main objective of this study was to evaluate if the -429T/C, -374T/A
      and 63 bp deletion polymorphisms in the RAGE gene are associated with diabetic
      retinopathy (DR) among Type 2 diabetic subjects in a clinic-based population from
      South India. METHODS: We screened 149 normal glucose tolerant subjects (NGT), 189
      Type 2 diabetes subjects without retinopathy (DM) and 190 subjects with DR for
      these polymorphisms using the PCR-RFLP method. DR was diagnosed by grading color
      fundus photography. Logistic regression models were used to evaluate the
      association of individual polymorphisms with DR. Expectation-maximization
      algorithms were implemented in haplotype tests of association to examine the
      combined effects of -429T/C and -374T/A polymorphisms on DR. RESULTS: The allelic
      frequencies of -429T are 0.83 in NGT, 0.84 in DM and 0.85 in DR subjects, and
      that of -374T are 0.93 in NGT, 0.92 in DM and 0.88 in DR subjects. The -374
      polymorphism was found to be associated with non-proliferative retinopathy when
      this subgroup was compared to the DM group (OR=1.814, 95% CI=1.005-3.273).
      However, this association was not obvious when both the subphenotypes of DR (the
      nonproliferative and proliferative DR groups) were studied jointly. We found no
      evidence for associations between the -429T/C polymorphism and the DR phenotype.
      Finally, extension to a 2-SNP haplotype did not reveal any significant
      statistical difference between the groups (P=0.668). CONCLUSION: In this study,
      we found a modest association with the -374T/A polymorphism in the
      nonproliferative DR subgroup.

PMID- 16440017
TI  - Charles Bonnet syndrome (visual hallucinations) following enucleation.

PMID- 16440018
TI  - Glutamate excitotoxicity in glaucoma: truth or fiction? By AJ Lotery.

PMID- 16440019
TI  - National survey of the technique of intravitreal triamcinolone injection in the
      United Kingdom.
AB  - OBJECTIVES: Intravitreal injection of steroids is a rapidly evolving treatment
      option for a variety of retinal pathologies. There is wide variation among
      ophthalmologists regarding dose of steroid and the technique of injection.
      Through this survey we aim to describe the current practice of injection of
      intravitreal steroid among ophthalmic consultants in the United Kingdom and
      review the literature. METHODS: A postal questionnaire was sent to all the 901
      ophthalmic consultants in the United Kingdom. The questions covered frequency of
      intravitreal steroid injections, subspecialty interest, dosage and volume of
      steroid, patient preparation, surgeon preparation, and postoperative management.
      RESULTS: The response rate to the questionnaire was 63%. A total of 24.7% perform
      intravitreal steroid injections regularly with 90% of users performing five or
      fewer injections per month. In all, 94% use a dose of 4 mg. Among surgeons, 38%
      do not prescribe postoperative antibiotics or steroids and 59% check intraocular
      pressure either on the same or the next day. CONCLUSION: The relatively short
      experience with this technique has not yet allowed a clear picture to emerge of
      indications, complications or best practice administration. Published
      descriptions of intravitreal steroid injection techniques vary widely and
      variations are not evidence based. Observed UK practice is diverse.

PMID- 16440020
TI  - UK retinopathy of prematurity treatment survey.
AB  - BACKGROUND: Since the CRYO-ROP study showed the benefit of treating babies with
      ROP, a number of different treatment modalities have become available. Solid
      state lasers have been extensively used in the treatment of ROP since their
      introduction some 10 years ago. Diode, argon and frequency-doubled YAG (FD-YAG)
      lasers have all been used to perform photocoagulation in ROP. We aimed to assess
      current treatment practices of ROP treatment in the UK. METHODS: A questionnaire
      survey was performed in June 2004 and sent to all consultants known to be
      involved in the treatment or screening of ROP patients. We asked about the number
      of patients treated in the last year, the treatment method, and whether there had
      been any serious complications. RESULTS: In all, 53 questionnaires were sent out,
      of which 42 were returned. Also, 30 respondents treated ROP. Of these 19 used
      transpupillary diode, 11 argon, and three FD-YAG. Cryotherapy and transscleral
      diode laser were used by two centres in particular cases. In all, 20 patients
      were treated with FD-YAG, 21 with argon laser, and 188 with diode laser. The
      number of burns per eye varied from 800 to 2500. Reported complications included
      hyphaema, retinal haemorrhage, and acute cataract formation; however, there was
      no significant difference in complications between different types of laser used.
      DISCUSSION: This survey of laser use in the treatment of ROP has shown that diode
      laser is now the most common mode of treatment in the UK. The incidence of
      complications was similar for centres using argon, diode, or FD-YAG laser.

PMID- 16440021
TI  - Bovine pericardium (Tutopatch) wrap for hydroxyapatite implants.
AB  - PURPOSE: To evaluate bovine pericardium (Tutopatch) as a wrapping material for
      hydroxyapatite implants in patients undergoing enucleation for uveal melanoma.
      METHOD: Prospective cohort study of patients who had enucleation for uveal
      melanoma between January 2003 and August 2003 were included in the study. Any
      patient with less than 3 months follow-up was excluded. Enucleation was performed
      under general anaesthesia followed by insertion of hydroxyapatite implants
      wrapped in bovine pericardium (Tutopatch). The recti muscles were sutured
      directly to the wrap. The tenon's capsule and conjunctiva were closed in two
      layers. A conformer was inserted at 1 week and artificial eye at 2-3 months. The
      patients were followed up regularly and were assessed for cosmetic result,
      exposure of implant, and the need for any further surgical procedures. RESULTS: A
      total of 19 patients (seven male and 12 female) were included in the study.
      Median age at diagnosis was 63 years (range 38-80 years). Median follow-up was 26
      months (range 22-30 months). No patient developed postoperative complications of
      wound dehiscence. The overall cosmetic result was excellent in all the patients.
      The rate of postoperative complications compared favourably with published data
      using other wrapping materials/implants. CONCLUSION: Tutopatch is a safe wrapping
      material for hydroxyapatite orbital implants in patients undergoing enucleation
      for uveal melanoma.

PMID- 16440022
TI  - ReGAE 1: using the Shah-Cross model as an orientating framework in African
      Caribbean glaucoma research.
AB  - The inter-relationship between health-care research, policy and service
      development is convoluted and difficult to articulate. This paper describes a
      framework for planning research into a range of ophthalmic conditions
      differentially associated with specific ethnic groups. It discusses the utility
      of the 'Shah-Cross Model' in mapping development of a glaucoma research project,
      and communicating its implications for local eye-care policy and ophthalmic
      services directed towards detection and management of primary open-angle glaucoma
      in the African-Caribbean population in the UK.

PMID- 16440023
TI  - Loose cilium in meibomian gland: mimicking early postoperative endophthalmitis.

PMID- 16440030
TI  - [Palliative medicine].

PMID- 16440029
TI  - [To find out or to think of--the little difference].

PMID- 16440032
TI  - [Prescription errors--dimension and measures].
AB  - BACKGROUND: A prescription should contain sufficient information to dispense the
      right medicine with correct instructions for use. The information given on the
      prescription also forms the basis for reimbursement of drug expenses. Knowledge
      of prescription errors may improve the procedures of the prescribing physician
      and the pharmacy. MATERIAL AND METHOD: Prescriptions without information on the
      indication of the drug therapy were registered in ten Norwegian pharmacies during
      two days in the autumn of 2004. Other errors and omissions on prescriptions were
      registered in nine of the pharmacies during a five week period. RESULTS AND
      INTERPRETATION: A total of 1884 (39%) of the 4667 prescriptions included in the
      first part of the study contained no information on the indication. A total of
      1696 other errors and omissions were registered on 1359 (2%) of the 69,315
      prescriptions included in the second part of the study. The most common errors
      and omissions were incomplete instructions for use (26%), missing information
      about the patient (17%), and errors and omissions related to reimbursement of
      drug expenses. 294 (17%) of the errors were judged to have potential clinical
      significance if they had not been corrected. The most common intervention was to
      interview the patient or to contact the prescribing physician. The most common
      changes were to change or clarify drug and dose.

PMID- 16440031
TI  - [Whooping cough--an old disease of current interest].

PMID- 16440033
TI  - [General practitioner and mental diseases among children and adolescents].
AB  - BACKGROUND: Child and adolescent psychiatry in primary health care is scarcely
      investigated. The purpose of this article is to describe some aspects of the role
      of the general practitioner in the care of young patients with psychiatric
      problems. MATERIAL AND METHODS: Data were collected from four focus group
      interviews with 19 general practitioners. The material was analysed in a
      phenomenological perspective. The aim was to develop new and documented
      descriptions seen from the participants' point of view, interpreted within the
      framework of available knowledge about care for children and adolescents with
      psychiatric problems. RESULTS AND INTERPRETATION: The general practitioner is in
      a good position to provide psychiatric care for these patients because of his or
      her unique knowledge about the families and the local communities. They have
      their patients' confidence and acquired skills from their unselected practice to
      recognise serious and abnormal conditions. The majority of the informants did not
      feel sufficiently skilled in order to treat more specific child and adolescent
      psychiatric disorders. Some informants were actively involved in
      multidisciplinary networks concerning their young patients, while others were
      neither involved nor informed about it. In addition, local health and welfare
      services to a lesser extent involved these doctors. Because of this, children and
      adolescents who might have been assessed and treated in primary health care could
      be referred directly to specialists. A need for guidance and updating on relevant
      knowledge from the specialist health care was expressed. From the results we
      might assume that specialists might give some general practitioners the
      professional security needed in order to take on the role of medical co
      coordinator of the multidisciplinary services to young patients with mental
      health problems.

PMID- 16440034
TI  - [Bipolar disorders in children and adolescents].
AB  - BACKGROUND: Bipolar disorders often develop in children and adolescents but are
      seldom diagnosed before adulthood. These illnesses are associated with
      considerable morbidity and mortality. The aim of this paper is to provide
      knowledge to facilitate earlier diagnosis. MATERIAL AND METHOD: Medline search.
      RESULTS: Bipolar disorders are characterised by serious fluctuations in energy
      and mood. The diagnosis of bipolar disorders in children and adolescents is
      challenging because the clinical presentation is influenced by ongoing neural
      development, which cause considerable symptom overlap and comorbidity with ADHD,
      conduct disorders, anxiety and Tourette's syndrome. ADHD symptoms may be a
      precursor of bipolar disorder among some of the youngest children, and
      prepubertal depression is often pre-bipolar.

PMID- 16440036
TI  - [Fish--more than just omega 3].
AB  - In the Norwegian governmental guidelines for food and nutrition, an increased
      intake of fish and other seafood is particularly recommended. Fish is a good
      source of many important nutrients, such as proteins, very long-chain omega 3
      fatty acids, vitamin D, vitamin B12, selenium and iodine. The beneficial effect
      on health by including fish has been documented in several studies. Increasing
      interest in the health gains obtained by regular fish intake has put emphasis on
      the need for documentation of both nutrients and contaminants in fish and
      seafood, with a balanced risk assessment. In this paper, some of the positive
      health effects of fish in the diet are elucidated.

PMID- 16440035
TI  - [Whooping cough--an increasing problem in Norway].
AB  - BACKGROUND: The incidence of whooping cough has increased in recent years in
      Norway, especially amongst older children and adults; in 2004 it was 168/100,000.
      MATERIAL AND METHODS: This article is based on our own experience and a review of
      available literature, identified on Medline with the search word "pertussis".
      RESULTS AND INTERPRETATION: Whooping cough, a disease caused by the bacterium
      Bordetella pertussis, is transmitted via respiratory droplets. Sources of
      infection for infants are often their parents and siblings. Older children and
      adolescents contract whooping cough mostly in school, whereas adults usually get
      the disease from children or colleagues. The typical symptoms are bouts of
      violent coughing with the classic whoop and post-tussive vomiting. A milder
      clinical picture can be seen in vaccinated persons, reinfected patients, and in
      persons above the age of 15. Infants are most at risk of developing serious
      disease and have the highest numbers of hospitalizations, complications and
      mortality. But complications are also seen in adolescents and adults, including
      urinary incontinence, rib fractures and pneumonia. The diagnosis is made by
      culture or PCR in nasopharyngeal secretions, as well as by detection of
      antibodies to B. pertussis in serum. If treatment is indicated, macrolides are
      the drugs of choice; these shorten the duration of symptoms and the period of
      contagiousness if given in the early stages of the disease. To help combat
      whooping cough in Norway, from 2006 an extra vaccine booster dose will be given
      to children at the age of seven.

PMID- 16440037
TI  - [Instructing patients in the correct use of inhalation devices].
AB  - BACKGROUND: Limited knowledge is available on to what extent doctors and nurses
      know the correct use of various inhalation devices. We wanted to examine this
      skill among 25 doctors and 25 nurses randomly selected from the departments of
      pulmonology, internal medicine and surgery at a university hospital. DESIGN: Two
      technicians asked them to demonstrate the correct use of a metered-dose inhaler
      (MDI), Turbuhaler and Diskus. The performance was checked against a list of
      criteria with a maximum obtainable score of 9 for each device. RESULTS: The mean
      (SD) scores for the MDI, Turbuhaler and Diskus were 2.6 (2.0), 2.9 (2.2) and 3.7
      (2.5), respectively. The score for the Diskus was significantly higher than those
      for the other two devices. The staff of the pulmonary department scored
      significantly higher than the staff of the other two departments, the scores for
      the pulmonary department being 4.1 (1.9), 4.8 (1.5) and 5.5 (1.5), respectively.
      The scores for the department of internal medicine were 2.4 (1.8), 2.7 (2.2) and
      3.4 (2.5), and the scores for the department of surgery were 1.5 (1.2), 1.4 (1.5)
      and 2.3 (2.5). INTERPRETATION: This study indicates that there is a significant
      potential for improvement in correct use of these inhalation devices.

PMID- 16440038
TI  - [Transient pseudohypoaldosteronism in infants with vesicoureteral reflux].
AB  - BACKGROUND: Congenital urologic malformations occur with an incidence of 1:100 to
      1: 200, leading to an increased risk of urinary tract infections. However, most
      patients remain without symptoms; serious electrolyte imbalance is rare. MATERIAL
      AND METHODS: We report two infants who were admitted to hospital because of
      failure to thrive and poor weight gain. Both children had severe hyponatraemia
      and hyperkalaemia. Further work-up established pseudohypoaldosteronism secondary
      to dilated vesicoureteral reflux and urinary tract infection. Based on a
      literature search in PubMed, a short overview of this rare condition is
      presented. RESULTS AND INTERPRETATION: Infants younger than 6 months of age with
      urologic malformations, and in most cases concomitant urinary tract infections,
      may develop secondary pseudohypoaldosteronism. The pathogenesis of this condition
      is probably a result of high intrarenal pressure, inflammation and immaturity of
      the tubular function leading to tubular resistance to aldosterone. The major
      symptoms are failure to thrive, poor weight gain, and signs of dehydration.
      Laboratory studies show hyponatraemia, hyperkalaemia and high levels of plasma
      renin activity and aldosterone. Treatment involves fluid resuscitation, sodium
      supplementation and antibiotic treatment of concomitant urinary tract infection.
      The most important differential diagnosis is the salt-losing form of congenital
      adrenal hyperplasia. A thorough endocrinologic and urological work-up, including
      abdominal ultrasound examination and urine analysis, may lead to correct
      diagnosis and treatment.

PMID- 16440039
TI  - [Use of estrogen replacement therapy and alternative therapies among Norwegian
      women aged 50-69].
AB  - BACKGROUND: Several large studies have showed higher risk and less benefit from
      hormone replacement therapy (HRT) than assumed, and sales figures have been
      reduced by almost a half. Several non-hormonal treatment alternatives for
      climacteric complaints are available. The object of this study was to determine
      the occurrence of climacteric complaints, and to study the use and efficacy of
      hormonal and alternative therapies among Norwegian women. MATERIAL AND METHODS:
      150 participants in the Norwegian Mammography Screening Programme in Trondheim
      were interviewed about climacteric symptoms, use of HRT, and of alternative
      therapies. RESULTS: 81% of the participants had experienced vasomotor symptoms.
      The prevalence was highest among women aged 55-59 years. 23% of the women were
      current users of HRT, 27% were past users. 75% of the HRT users reported good
      effect. 25% of the participants were current users of alternative therapies,
      while 17% were past users. Soy was most frequently used as an alternative
      therapy. 42% of the alternative therapies were reported to be effective.
      INTERPRETATION: Half of the participants had used HRT, and most of these reported
      good effect. A corresponding number of women had used various alternative
      therapies, but the perceived efficacy of these was significantly poorer.

PMID- 16440040
TI  - [Local treatment of atopic dermatitis with calcineurin inhibitors].

PMID- 16440041
TI  - [The specialist field of palliative medicine].
AB  - Palliative medicine means caring for patients with incurable disease and short
      life expectancy, or, with the British definition, "the study and management of
      patients with active, progressive, far advanced disease, for whom the prognosis
      is limited and the focus of care is the quality of life". Palliative medicine is
      more than care for the dying. Today palliative medicine is regarded as integral
      to the treatment pathway for all patients with incurable disease. Up to now,
      mostly cancer patients have been offered specialist palliative care, but the
      international trend is to include other patient groups, especially patients with
      degenerative neurological disease and advanced cardiac and pulmonary disease.
      Palliative medicine is characterized by a focus not primarily on disease control
      but rather on symptom relief, social support, spiritual care, and maintenance of
      physical and psychological functioning and wellbeing. To reach these goals, a
      multi-professional approach is needed, and the doctor in charge must be highly
      qualified clinically and academically and willing and able to cooperate with
      colleagues and other healthcare professionals.

PMID- 16440042
TI  - [Organisation of palliative care in and outside hospital].
AB  - Patients with advanced, incurable disease need easy access to qualified care.
      Basic palliative care should be provided in all clinical hospital departments and
      in community care. In addition, palliative care units in hospitals and nursing
      homes, and ambulatory, multidisciplinary, palliative care teams have a supportive
      role by providing teaching, advice, and care, also in primary care. The regional
      palliative care centres in university hospitals are important centres for
      research, skills building, and developmental work, in addition to the management
      of the most complex patients. Palliative care requires much collaboration, and
      the general practitioner has an important role. In addition, hospital-based
      palliative care teams are important bridges between the different levels of the
      health care system. The Norwegian Standard for Palliative Care gives
      recommendations for the organisation of palliative care at all levels, and forms
      the basis for this article.

PMID- 16440043
TI  - [Palliative medicine-- research and education in a new specialist field].
AB  - Palliative medicine has developed into a recognised specialty in medicine,
      calling for a high level of skills as well as evidence-based clinical guidelines.
      The undergraduate teaching in medical schools in Norway is fragmented in this
      area, and national minimum standards are needed. At the graduate level, teaching
      in palliative medicine should be included in all relevant specialties. Doctors
      who are fully involved in palliative medicine should have a specialised
      education. Recently, a Nordic Curriculum in Palliative Medicine was developed and
      a two-year course initiated; 30 doctors have graduated. There is a need for
      research in palliative care, both on the basic biological level as well as on the
      clinical level. National and international collaboration is needed in order to
      reach these goals. Nationally, there are some research groups that perform
      excellently. However, there is a need to strengthen research in this area. Chairs
      in palliative medicine will facilitate such a development and are urgently needed
      in all medical schools.

PMID- 16440044
TI  - [Beds for patients in palliative care at a surgery department].

PMID- 16440045
TI  - [Intermediate care beds at a surgery department].

PMID- 16440048
TI  - [A research institute or a center for opinion?].

PMID- 16440046
TI  - [Snowmobile injuries].

PMID- 16440052
TI  - [Disease treatment by nurses in Botswana].

PMID- 16440053
TI  - [Proper management of infections].

PMID- 16440055
TI  - Retroviral elements and their hosts: insertional mutagenesis in the mouse germ
      line.
AB  - The inbred mouse is an invaluable model for human biology and disease.
      Nevertheless, when considering genetic mechanisms of variation and disease, it is
      important to appreciate the significant differences in the spectra of spontaneous
      mutations that distinguish these species. While insertions of transposable
      elements are responsible for only approximately 0.1% of de novo mutations in
      humans, the figure is 100-fold higher in the laboratory mouse. This striking
      difference is largely due to the ongoing activity of mouse endogenous retroviral
      elements. Here we briefly review mouse endogenous retroviruses (ERVs) and their
      influence on gene expression, analyze mechanisms of interaction between ERVs and
      the host cell, and summarize the variety of mutations caused by ERV insertions.
      The prevalence of mouse ERV activity indicates that the genome of the laboratory
      mouse is presently behind in the "arms race" against invasion.

PMID- 16440058
TI  - Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts
      in the Shumiya cataract rat.
AB  - The Shumiya cataract rat (SCR) is a hereditary cataractous strain. It is thought
      that the continuous occurrence of poorly differentiated epithelial cells at the
      bow area of the lens forms the pathophysiological basis for cataract formation in
      SCRs. In this study, we attempted to identify the genes associated with cataract
      formation in SCRs by positional cloning. Genetic linkage analysis revealed the
      presence of a major cataract locus on chromosome 20 as well as a locus on
      chromosome 15 that partially suppressed cataract onset. Hypomorphic mutations
      were identified in genes for lanosterol synthase (Lss) on chromosome 20 and
      farnesyl diphosphate farnesyl transferase 1 (Fdft1) on chromosome 15, both of
      which function in the cholesterol biosynthesis pathway. A null mutation for Lss
      was also identified. Cataract onset was associated with the specific combination
      of Lss and Fdft1 mutant alleles that decreased cholesterol levels in cataractous
      lenses to about 57% of normal. Thus, cholesterol insufficiency may underlie the
      deficient proliferation of lens epithelial cells in SCRs, which results in the
      loss of homeostatic epithelial cell control of the underlying fiber cells and
      eventually leads to cataractogenesis. These findings may have some relevance to
      other types of cataracts, inborn defects of cholesterol synthesis, and the
      effects of cholesterol-lowering medication.

PMID- 16440056
TI  - Genetic analysis of the cytoplasmic dynein subunit families.
AB  - Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins
      of the cell, are involved in many essential cellular processes. The major form of
      this enzyme is a complex of at least six protein subunits, and in mammals all but
      one of the subunits are encoded by at least two genes. Here we review current
      knowledge concerning the subunits, their interactions, and their functional roles
      as derived from biochemical and genetic analyses. We also carried out extensive
      database searches to look for new genes and to clarify anomalies in the
      databases. Our analysis documents evolutionary relationships among the dynein
      subunits of mammals and other model organisms, and sheds new light on the role of
      this diverse group of proteins, highlighting the existence of two cytoplasmic
      dynein complexes with distinct cellular roles.

PMID- 16440057
TI  - Genetic analysis of completely sequenced disease-associated MHC haplotypes
      identifies shuffling of segments in recent human history.
AB  - The major histocompatibility complex (MHC) is recognised as one of the most
      important genetic regions in relation to common human disease. Advancement in
      identification of MHC genes that confer susceptibility to disease requires
      greater knowledge of sequence variation across the complex. Highly duplicated and
      polymorphic regions of the human genome such as the MHC are, however, somewhat
      refractory to some whole-genome analysis methods. To address this issue, we are
      employing a bacterial artificial chromosome (BAC) cloning strategy to sequence
      entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype
      Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3
      DQ2) and compare it with the MHC reference haplotype and with a second haplotype,
      COX (HLA-A1-B8-Cw7-DR3-DQ2), that shares the same HLA-DRB1, -DQA1, and -DQB1
      alleles. We have defined the complete gene, splice variant, and sequence
      variation contents of all three haplotypes, comprising over 259 annotated loci
      and over 20,000 single nucleotide polymorphisms (SNPs). Certain coding sequences
      vary significantly between different haplotypes, making them candidates for
      functional and disease-association studies. Analysis of the two DR3 haplotypes
      allowed delineation of the shared sequence between two HLA class II-related
      haplotypes differing in disease associations and the identification of at least
      one of the sites that mediated the original recombination event. The levels of
      variation across the MHC were similar to those seen for other HLA-disparate
      haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and 
      DQB1 genes and showed very limited polymorphism compatible with identity-by
      descent and relatively recent common ancestry (<3,400 generations). These results
      indicate that the differential disease associations of these two DR3 haplotypes
      are due to sequence variation outside this central 158-kb segment, and that
      shuffling of ancestral blocks via recombination is a potential mechanism whereby
      certain DR-DQ allelic combinations, which presumably have favoured immunological
      functions, can spread across haplotypes and populations.

PMID- 16440059
TI  - Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of
      multiple sclerosis.
AB  - Inflammatory diseases of the CNS, such as MS and its animal model EAE, are
      characterized by infiltration of activated lymphocytes and phagocytes into the
      CNS. Within the CNS, activation of resident cells initiates an inflammatory
      cascade, leading to tissue destruction, demyelination, and neurologic deficit.
      TLRs recognize microbes and are pivotal mediators of innate immunity. Within the
      CNS, augmented TLR expression during EAE is observed, even in the absence of any
      apparent microbial involvement. To determine the functional relevance of this
      phenomenon during sterile autoimmunity, we studied the role of different TLRs as
      well as their common signaling adaptor MyD88 in the development of EAE. We found
      that MyD88 mice were completely EAE resistant. Surprisingly, this protection is
      partly due to engagement of the CpG receptor TLR9. Restricting the MyD88 or TLR9
      mutation to host radio-resistant cells, including the cells within the CNS,
      revealed that engagement of radio-resistant cells modulated the disease course
      and histopathological changes. Our data clearly demonstrate that both TLR9 and
      MyD88 are essential modulators of the autoimmune process during the effector
      phase of disease and suggest that endogenous "danger signals" modulate the
      disease pathogenesis.

PMID- 16440060
TI  - Glucocorticoids exacerbate obesity and insulin resistance in neuron-specific
      proopiomelanocortin-deficient mice.
AB  - Null mutations of the proopiomelanocortin gene (Pomc) cause obesity in humans and
      rodents, but the contributions of central versus pituitary POMC deficiency are
      not fully established. To elucidate these roles, we introduced a POMC transgene
      (Tg) that selectively restored peripheral melanocortin and corticosterone
      secretion in Pomc mice. Rather than improving energy balance, the genetic
      replacement of pituitary POMC in PomcTg mice aggravated their metabolic syndrome
      with increased caloric intake and feed efficiency, reduced oxygen consumption,
      increased subcutaneous, visceral, and hepatic fat, and severe insulin resistance.
      Pair-feeding of PomcTg mice to the daily intake of lean controls normalized their
      rate of weight gain but did not abolish obesity, indicating that hyperphagia is a
      major but not sole determinant of the phenotype. Replacement of corticosterone in
      the drinking water of Pomc mice recapitulated the hyperphagia, excess weight gain
      and fat accumulation, and hyperleptinemia characteristic of genetically rescued
      PomcTg mice. These data demonstrate that CNS POMC peptides play a critical role
      in energy homeostasis that is not substituted by peripheral POMC. Restoration of
      pituitary POMC expression to create a de facto neuronal POMC deficiency
      exacerbated the development of obesity, largely via glucocorticoid modulation of
      appetite, metabolism, and energy partitioning.

PMID- 16440061
TI  - Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite
      derivatives under cystic fibrosis airway conditions.
AB  - Mucoid, mucA mutant Pseudomonas aeruginosa cause chronic lung infections in
      cystic fibrosis (CF) patients and are refractory to phagocytosis and antibiotics.
      Here we show that mucoid bacteria perish during anaerobic exposure to 15 mM
      nitrite (NO2) at pH 6.5, which mimics CF airway mucus. Killing required a pH
      lower than 7, implicating formation of nitrous acid (HNO2) and NO, that adds NO
      equivalents to cellular molecules. Eighty-seven percent of CF isolates possessed
      mucA mutations and were killed by HNO2 (3-log reduction in 4 days). Furthermore,
      antibiotic-resistant strains determined were also equally sensitive to HNO2. More
      importantly, HNO2 killed mucoid bacteria (a) in anaerobic biofilms; (b) in vitro
      in ultrasupernatants of airway secretions derived from explanted CF patient
      lungs; and (c) in mouse lungs in vivo in a pH-dependent fashion, with no
      organisms remaining after daily exposure to HNO2 for 16 days. HNO2 at these
      levels of acidity and NO2 also had no adverse effects on cultured human airway
      epithelia in vitro. In summary, selective killing by HNO2 may provide novel
      insights into the important clinical goal of eradicating mucoid P. aeruginosa
      from the CF airways.

PMID- 16440062
TI  - Connexin43-dependent mechanism modulates renin secretion and hypertension.
AB  - To investigate the function of Cx43 during hypertension, we studied the mouse
      line Cx43KI32 (KI32), in which the coding region of Cx32 replaces that of Cx43.
      Within the kidneys of homozygous KI32 mice, Cx32 was expressed in cortical and
      medullary tubules, as well as in some extra- and intraglomerular vessels, i.e.,
      at sites where Cx32 and Cx43 are found in WT mice. Under such conditions, renin
      expression was much reduced compared with that observed in the kidneys of WT and
      heterozygous KI32 littermates. After exposure to a high-salt diet, all mice
      retained a normal blood pressure. However, whereas the levels of renin were
      significantly reduced in the kidneys of WT and heterozygous KI32 mice, reaching
      levels comparable to those observed in homozygous littermates, they were not
      further affected in the latter animals. Four weeks after the clipping of a renal
      artery (the 2-kidney, 1-clip [2K1C] model), 2K1C WT and heterozygous mice showed
      an increase in blood pressure and in the circulating levels of renin, whereas
      2K1C homozygous littermates remained normotensive and showed unchanged plasma
      renin activity. Hypertensive, but not normotensive, mice also developed cardiac
      hypertrophy. The data indicate that replacement of Cx43 by Cx32 is associated
      with decreased expression and secretion of renin, thus preventing the renin
      dependent hypertension that is normally induced in the 2K1C model.

PMID- 16440064
TI  - Influenza pandemics: past, present and future.
AB  - Influenza A virus is well known for its capability for genetic changes either
      through antigen drift or antigen shift. Antigen shift is derived from
      reassortment of gene segments between viruses, and may result in an antigenically
      novel virus that is capable of causing a worldwide pandemic. As we trace
      backwards through the history of influenza pandemics, a repeating pattern can be
      observed, namely, a limited wave in the first year followed by global spread in
      the following year. In the 20th century alone, there were three overwhelming
      pandemics, in 1918, 1957 and 1968, caused by H1N1 (Spanish flu), H2N2 (Asian flu)
      and H3N2 (Hong Kong flu), respectively. In 1957 and 1968, excess mortality was
      noted in infants, the elderly and persons with chronic diseases, similar to what
      occurred during interpandemic periods. In 1918, there was one distinct peak of
      excess death in young adults aged between 20 and 40 years old; leukopenia and
      hemorrhage were prominent features. Acute pulmonary edema and hemorrhagic
      pneumonia contributed to rapidly lethal outcome in young adults. Autopsies
      disclosed multiple-organ involvement, including pericarditis, myocarditis,
      hepatitis and splenomegaly. These findings are, in part, consistent with clinical
      manifestations of human infection with avian influenza A H5N1 virus, in which
      reactive hemophagocytic syndrome was a characteristic pathologic finding that
      accounted for pancytopenia, abnormal liver function and multiple organ failure.
      All the elements of an impending pandemic are in place. Unless effective measures
      are implemented, we will likely observe a pandemic in the coming seasons. Host
      immune response plays a crucial role in disease caused by newly emerged influenza
      virus, such as the 1918 pandemic strain and the recent avian H5N1 strain.
      Sustained activation of lymphocytes and macrophages after infection results in
      massive cytokine response, thus leading to severe systemic inflammation. Further
      investigations into how the virus interacts with the host's immune system will be
      helpful in guiding future therapeutic strategies in facing influenza pandemics.

PMID- 16440065
TI  - Change of potassium current density in rabbit corneal epithelial cells during
      maturation and cellular senescence.
AB  - BACKGROUND: Voltage-gated potassium (K+) channels may participate in cellular
      developmental regulation, including cell differentiation, proliferation and
      apoptosis. This study investigated the change of K + current densities in corneal
      epithelial cells during maturation and cellular senescence. METHODS: New Zealand
      white rabbits were divided into three age groups: newborn (<or= 7 days old, n =
      18); young (8-12 weeks old, n = 59); and adult (20-28 weeks old, n = 16). Rabbit
      corneal epithelial cells were subdivided into the following three groups: small
      cells with capacitance < 6.0 pF; medium cells with capacitance 6.0-10.0 pF; and
      large cells with capacitance > 10.0 pF. Using a whole-cell clamp technique, K+
      current was recorded and current densities were calculated. Differences in K+
      current densities among newborn, young and adult rabbits, as well as differences
      among small, medium and large cells, were analyzed. RESULTS: We delineated two
      types of cells manifesting different amplitudes of depolarization-activated K+
      outward currents. The averaged current density of type 1 response cells was
      significantly larger than that of type 2 cells in newborn, young, and adult
      groups. For newborn epithelial cells, the depolarization-gated outward K+ current
      density decreased from small to medium to large cells (p = 0.049, at a membrane
      potential of 140 mV). A similar pattern of change in current density was also
      delineated for these cell sizes in young and adult rabbit corneal cells (p <
      0.001 for both young and adult rabbits). An increase in depolarization-gated
      outward K+ current density was also delineated from newborn to young to adult
      rabbits (p < 0.001, p < 0.001 and p < 0.006 for small, medium and large cells,
      respectively, at a membrane potential of 140 mV). CONCLUSIONS: Corneal epithelial
      cells expressed K+ channel densities that were distinct from basal to superficial
      cells and from newborn to adult rabbits.

PMID- 16440066
TI  - Dyslipidemia is associated with ventricular tachyarrhythmia in patients with
      acute ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Ventricular tachyarrhythmia developing in the acute stage of
      myocardial infarction (MI) is an important cause of sudden cardiac death. The aim
      of this study was to determine whether dyslipidemia is associated with the
      occurrence of ventricular tachycardia/fibrillation (VT/VF) during the acute stage
      of ST-segment elevation MI (STEMI). METHODS: A total of 58 patients experiencing
      VT/VF within 24 hours after the onset of MI were selected as the study group. A
      group of 58 patients with MI but without VT/VF was selected as the control group
      matched for sex (overall, 104 males), age (overall, 58 +/- 10 years), and the use
      of thrombolytic therapy (n = 82). The lipid profiles including total cholesterol
      (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein
      cholesterol (LDL-C), and triglyceride were measured during the first week and at
      the third month after the index MI. Other coronary risk factors, and clinical,
      hemodynamic and angiographic characteristics were also included in the
      assessment. RESULTS: During the acute stage, patients with VT/VF had higher
      levels of LDL-C and lower blood pressure on initial arrival at our hospital. At
      the 3-month follow-up, those patients with VT/VF showed higher levels of TC, LDL
      C and triglyceride. Multivariate analysis revealed that LDL-C (p < 0.001) at the
      3-month follow-up, mean blood pressure on arrival (p < 0.01), and the difference
      in triglyceride levels between the first week and the third month (p < 0.05) were
      independent predictors for the occurrence of VT/VF in the acute stage of MI.
      CONCLUSION: This study suggests that dyslipidemia imposes a higher risk of
      developing tachyarrhythmia in the acute phase of STEMI.

PMID- 16440063
TI  - Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes
      to the variation in efficacy of sublingual nitroglycerin.
AB  - Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat
      angina and heart failure for more than 130 years. Recently, it was shown that
      mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of
      NO, the metabolite needed for GTN efficacy. In the present study, we show that
      the common G-to-A polymorphism in exon 12 of ALDH2--resulting in a Glu504Lys
      replacement that virtually eliminates ALDH2 activity in both heterozygotes and
      homozygotes--is associated with a lack of efficacy of sublingual GTN in Chinese
      subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism
      of the Glu504 protein is approximately 10-fold higher than that of the Lys504
      enzyme. We conclude that the presence of the Lys504 allele contributes in large
      part to the lack of an efficacious clinical response to nitroglycerin; we
      recommend that this genetic factor be considered when administering nitroglycerin
      to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2
      mutant allele.

PMID- 16440067
TI  - Age transition of tuberculosis patients in Taiwan, 1957-2001.
AB  - BACKGROUND: The incidence of tuberculosis (TB) has been falling in many developed
      countries; however, there is a trend of an increasing proportion of TB among the
      elderly. The aim of this study was to evaluate the age transition of patients
      with TB in Taiwan from 1957 to 2001. METHODS: Data on the number of TB cases and
      patient age were collected from the National Tuberculosis Registry for three
      different 5-year periods: 1957-1961, 1977-1981, and 1997-2001. The distribution
      of TB cases in these three different periods was analyzed. RESULTS: The age
      distributions of TB patients were different among the 1957-61 (n = 26,000), 1977
      81 (n = 31,363) and 1997-2001 (n = 71,447) groups. During the 1957-61 period, the
      most common age group was 25-44 years (50.9%). During 1977-81, the most common
      age group was 45-64 years (44.9%). In 1997-2001, the most common age group had
      shifted to people aged 65 years or older (43.7%). For the whole period from 1957
      to 2001, after adjusting for age shifts in the general population, the proportion
      of TB patients had significantly increased in persons 65 years or older, slightly
      increased in persons aged 0-14 years, and decreased in the 15-24, 25-44, and 45
      64-year-old age groups. For the period 1977-2001, age-specific registered case
      rates increased with age. CONCLUSION: The age of TB patients in Taiwan showed a
      rising trend from 1957 to 2001. A high index of suspicion and prompt
      investigation of elderly patients with signs and symptoms characteristic of TB
      may allow earlier diagnosis and treatment.

PMID- 16440068
TI  - Declining emergency department visits and costs during the severe acute
      respiratory syndrome (SARS) outbreak.
AB  - BACKGROUND: The immediate and long-term impact of severe acute respiratory
      syndrome (SARS) outbreak on emergency department (ED) visits and hospital
      expenditures for these visits has not been thoroughly investigated. The
      objectives of this retrospective observational study investigated the impact of
      SARS outbreak on ED visits and the cost of these visits in a designated SARS
      medical center. METHODS: Data related to the total number of ED visits and their
      costs were collected for the SARS epidemic period in 2003 and the same period in
      the preceding year in 2002. Data collected included total number of ED visits,
      services provided, triage categories, and total expenditures for all patients.
      Data for before and during the outbreak were retrieved and compared. RESULTS: At
      the peak of the SARS epidemic, the reduction in daily ED visits reached 51.6% of
      pre-epidemic numbers (p < 0.01). In pediatric, trauma and non-trauma patients,
      the maximum mean decreases in number of visits were 80.0% (p < 0.01), 57.6% (p <
      0.01) and 40.8% (p < 0.01), respectively. In triage 1, 2 and 3 patients, the
      maximum mean decreases were 18.1% (p < 0.01), 55.9% (p < 0.01) and 53.7% (p <
      0.01), respectively. The maximum decrease in total costs was 37.7% (p < 0.01).
      The maximum mean costs per patient increased 35.9% (p < 0.01). The proportions of
      increases in mean costs for each patient were attributed to laboratory
      investigations (31.4%), radiography (21.9%) and medications (29.5%). CONCLUSION:
      The SARS outbreak resulted in a marked reduction in the number of ED visits which
      persisted for 3 months after the end of the epidemic. Total cost of treating
      individual patients showed a simultaneous marked increase, while overall
      operational costs in the ED showed a marked decrease. The increased total cost
      for each patient was attributed to the increased number of diagnostic procedures
      to screen for possible SARS in the ED.

PMID- 16440069
TI  - Febrile convulsions: development and validation of a questionnaire to measure
      parental knowledge, attitudes, concerns and practices.
AB  - BACKGROUND: The best medicine for febrile convulsions (FCs) is not prescription
      medications but effective communication of related information to parents.
      Therefore, a quick assessment tool for obtaining information about parental
      responses to FCs is essential for educating parents, clinical practice and
      research. This paper describes the development and psychometric testing of a
      questionnaire on parental knowledge, attitudes, concerns and practices (KACP)
      toward FC. METHODS: Questionnaire items were created via literature review,
      interview, and expert consultation. Ten parents were interviewed to develop the
      questionnaire contents. Nine experts and seven parents were consulted to review
      the content and face validity of the questionnaire. Of the 326 parents of
      children with FC visiting 11 emergency departments in southern Taiwan, 216
      parents completed the questionnaire, and 64 completed the questionnaire again 2
      weeks later. Content validity, internal consistency, test-retest reliability, and
      item analysis were evaluated. RESULTS: Cronbach's alpha exceeded 0.72 for the
      knowledge, attitudes and concerns domains. The item-total correlations in the
      knowledge and concerns domains ranged from 0.40 to 0.73, but were lower in the
      attitudes domain (only 4 in 10 items were within 0.40-0.70). The intraclass
      correlation coefficients (ICC) for the test-retest reliability of the knowledge,
      attitudes and concerns domains were 0.65, 0.68 and 0.58, respectively. The
      correlation coefficients between KACP domains were tested and significantly
      supported the theoretical basis of the questionnaire. CONCLUSION: For research
      purposes, the KACP questionnaire measures parental responses with a moderate
      level of reliability and validity. Cross-cultural investigation of the
      questionnaire is needed to facilitate its use in other countries.

PMID- 16440070
TI  - Etiology and cytokine expression in patients requiring mechanical ventilation due
      to severe community-acquired pneumonia.
AB  - BACKGROUND: The relationship between bacterial etiology and serum cytokine levels
      in patients with severe community-acquired pneumonia (CAP) without response to
      initial empiric treatment remains unclear. This study investigated the bacterial
      etiology, outcomes, and bronchoalveolar and systemic cytokines (interleukin [IL]
      1beta, IL-8, IL-10) in these patients. METHODS: This hospital-based study
      enrolled 47 consecutive patients without response to initial empiric treatment
      and requiring mechanical ventilation due to severe CAP between July 1, 2000 and
      October 31, 2001, in a respiratory intensive care unit of a 1200-bed teaching
      hospital in central Taiwan. Bronchoalveolar lavage (BAL) was performed within 3
      days after hospitalization. BAL fluid was processed for quantitative bacterial
      cultures. Blood samples were taken just before BAL, and the levels of both BAL
      and serum cytokines were measured. RESULTS: The most common pathogens isolated
      were Pseudomonas aeruginosa (22.5%) and Klebsiella pneumoniae (25%). Patients
      with a K. pneumoniae isolate (n = 10) had significantly higher levels of IL-1beta
      in BAL fluid and significantly higher levels of IL-10 in serum and BAL fluid than
      patients with other etiologies. Non-survivors had higher levels of serum IL-8 (p
      = 0.001), serum IL-10 (p < 0.001) and BAL IL-10 (p = 0.039) than survivors.
      Marked increases in local and systemic cytokine expression (IL-8 and IL-10) were
      noted in rapidly fatal cases. CONCLUSION: P. aeruginosa and K. pneumoniae are the
      most common causes of CAP requiring mechanical ventilation in Taiwan. Cytokine
      patterns in the BAL fluid and serum of patients with severe CAP due to K.
      pneumoniae showed significant elevations compared to other pathogens.
      Bronchoalveolar and systemic cytokine levels (especially IL-10) predicted
      mortality. These findings suggest the need for a clinical trial to determine how
      immunomodulating therapy might affect cytokine profiles and clinical outcome.

PMID- 16440071
TI  - Overweight and obesity-related metabolic disorders in hospital employees.
AB  - BACKGROUND: Obesity is associated with metabolic disorders and cardiovascular
      diseases. This study investigated the relationship between overweight and obese
      status and the incidence of type 2 diabetes, hypertension, hyperlipidemia and
      hyperuricemia. METHODS: This prospective cohort study comprised 1749 hospital
      employees who received baseline health check-ups in 1993. Data from the 1027
      participants (832 women, 195 men; mean age, 36 +/- 7 years) who repeated check
      ups in 2003 were used in the analysis. Relative risks (RRs) for development of
      metabolic disorders during follow-up associated with different body mass index
      (BMI) categories at baseline as defined by Asia-Pacific recommendations and the
      Department of Health in Taiwan were calculated after adjustment for covariates.
      RESULTS: The prevalence of overweight and obesity at baseline check-up were 17.6%
      and 14.5%, respectively. Obese subjects with baseline BMI >or= 25 kg/m2 had a
      significant multivariate-adjusted RR of 2.7 for hypertension, 14.8 for type 2
      diabetes, 3.2 for hypertriglyceridemia, and 2.8 for hyperuricemia, compared to
      subjects with baseline BMI < 23.0 kg/m2. RR for diabetes was higher in women than
      in men, but RR for hypertriglyceridemia was higher in men. The risks of
      hypertension and hyperuricemia significantly increased for subjects with baseline
      BMI >or= 23 kg/m2, while RRs for type 2 diabetes increased significantly for
      baseline BMI >or= 24 kg/m2 and hypertriglyceridemia increased for baseline BMI
      >or= 25 kg/m2. The risks attributable to obesity (baseline BMI >or= 25 kg/m2)
      were 23.0% for hypertension, 70.8% for diabetes, 27.9% for hypertriglyceridemia,
      and 24.1% for hyperuricemia. CONCLUSION: This study revealed that a high
      prevalence of overweight and obesity was associated with significantly increased
      risk of development of type 2 diabetes, hypertension, hypertriglyceridemia and
      hyperuricemia in hospital employees, suggesting the need for programs to improve
      weight management.

PMID- 16440072
TI  - Quality of sleep and related factors during chemotherapy in patients with stage
      I/II breast cancer.
AB  - BACKGROUND: Insomnia causes severe distress in patients with breast cancer who
      receive chemotherapy. Few studies have focused on using objective methods to
      assess sleep. This study explored the quality of sleep and related factors in
      patients with breast cancer during chemotherapy. METHODS: The participants were
      16 women with stage I or II breast cancer receiving their third cycle of
      chemotherapy with cyclophosphamide, epirubicin and fluorouracil, or
      cyclophosphamide, methotrexate and fluorouracil. The effects of chemotherapy on
      sleep were assessed on the 8th and 9th days of the third cycle, i.e. the active
      phase in terms of side effects, and the last 2 days before the start of the
      fourth cycle for comparison. Instruments used to assess sleep quality and related
      factors included actigraphy, the Hospital Anxiety and Depression Scale (HADS),
      the Symptom Distress Scale (SDS), the Fatigue Visual Analogue Scale (FVAS), the
      Epworth Sleepiness Scale (ESS), and sleep logs. RESULTS: During the active phase,
      patients showed an anxiety tendency with an average HADS score of 7.8 +/- 3.8.
      The average FVAS score was 4 +/- 2, indicative of mild fatigue, and SDS score
      (1.8 +/- 0.3) also indicated mild symptom distress. The number of awakenings each
      night was 2.2 +/- 1.6 by sleep logs, and the total time spent awake during these
      episodes was 47.8 +/- 26.1 minutes by Actiwatch. Sleep efficiency measured by
      Actiwatch in the active phase was 82.1 +/- 9.4% below the normal limit. Daytime
      sleepiness assessed by ESS showed mild sleepiness (6.0 +/- 3.5) in the active
      phase. CONCLUSION: The study showed poor sleep quality and daytime sleepiness in
      patients with breast cancer during the active phase of chemotherapy. Chemotherapy
      may bring symptom distress to patients and adversely influence sleep quality.

PMID- 16440074
TI  - Melnick-Needles syndrome with obstructive sleep apnea successfully treated with
      nasal continuous positive airway pressure ventilation.
AB  - Melnick-Needles syndrome is a rare disorder characterized by short stature,
      prominent forehead, bilateral exophthalmos, fullness of the cheeks and
      retrognathia. We report a 31-year-old female with Melnick-Needles syndrome
      complicated with severe obstructive sleep apnea syndrome (OSAS). Polysomnography
      demonstrated a respiratory disturbance index of 76.8/hour. Severe restrictive
      ventilatory impairment was also evident on pulmonary function tests. Surgical
      correction of the upper airway failed to improve OSAS symptoms, but nasal
      continuous positive airway pressure (CPAP) ventilation successfully improved both
      OSAS and restrictive ventilatory impairment. OSAS should be excluded in patients
      with Melnick-Needles syndrome and, if diagnosed, nasal CPAP may be a helpful
      treatment.

PMID- 16440073
TI  - Outcome of percutaneous transarterial coil occlusion in patients with isolated
      patent ductus arteriosus using an upstream-and-push maneuver.
AB  - BACKGROUND: There are limited data on the outcome of percutaneous transarterial
      coil occlusion for isolated patent ductus arteriosus (PDA) in Taiwan. This study
      evaluated the 2-year outcome of 52 patients with isolated PDA who received
      percutaneous transarterial coil occlusion by an upstream-and-push maneuver.
      METHODS: From July 1997 to June 2002, a total of 52 patients (25 infants, 27
      children) underwent occlusion of PDA with standard Gianturco coils. There were 39
      females and 13 males. Patient age ranged between 7 days and 14 years, and weight
      was between 3 and 45 kg. Percutaneous transarterial coil occlusion was performed
      by an upstream-and-push maneuver. Chest auscultations, chest radiographs, and
      Doppler echocardiography were performed in all patients within 24 hours, and 1,
      3, 6, 12 and 24 months after coil occlusion. RESULTS: Mean PDA diameter at the
      pulmonary end was 2.34 +/- 1.00 mm (range, 1.00-4.80 mm). Angiographic
      classification was megaphone type in 32 patients, window type in seven, tubular
      type in six, aneurysmal type in three, and elongated conical type in four.
      Complete PDA occlusion was performed with a single coil in 41 (79%) patients and
      with multiple coils in 11 (21%). The mean ratio of pulmonary to systemic blood
      flow was 1.95 +/- 0.95 (range, 1.10-5.80) before the procedure, and 1.02 +/- 0.04
      (range, 1.00-1.20) after the procedure (p < 0.001). Immediate occlusion of the
      ductus was achieved 15 minutes after the procedure in 44 (85%) patients.
      Occlusion was achieved in 92% of patients within 24 hours and in 100% of patients
      by the 1-month follow-up. Follow-up at 24 months after the procedure revealed no
      complications. CONCLUSION: Percutaneous transarterial coil occlusion with 5-loop
      Gianturco coils can be effectively and safely achieved in patients with a PDA
      minimum diameter < 5 mm.

PMID- 16440075
TI  - Fatal massive hemorrhage caused by nasogastric tube misplacement in a patient
      with mediastinitis.
AB  - Nasogastric tube insertion is a routine procedure in medical care. However,
      misplacement of the tube can cause a variety of complications, which can be life
      threatening in some instances. We report a case of fatal hemorrhagic shock
      immediately after nasogastric tube insertion in a patient undergoing debridement
      by video-assisted thoracoscopic surgery for mediastinitis. Emergency endoscopy
      showed that the bleeding came from the nasogastric tube which had perforated the
      esophagus and possibly tore an intrathoracic large vessel. The nasogastric tube
      insertion was considered to have directly produced the perforation because no
      esophageal perforation had been found on preoperative endoscopy. Factors
      contributing to the risk of esophageal perforation in this case included
      coexisting mediastinitis, surgical manipulation, endotracheal intubation,
      inability to cooperate during general anesthesia, and repetitive advancement of
      the nasogastric tube. Prompt clamping of the nasogastric tube or delayed
      insertion after failed attempts might have improved the outcome. This report
      illustrates the complication of massive bleeding that can occur immediately after
      misplaced insertion of a nasogastric tube. Extraordinary care should be taken to
      avoid misplacement of the nasogastric tube during insertion.

PMID- 16440077
TI  - Neuroleptic malignant syndrome after the use of venlafaxine in a patient with
      generalized anxiety disorder.
AB  - Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse reaction to
      neuroleptics, which is characterized by hyperthermia, extrapyramidal symptoms,
      altered consciousness and autonomic dysfunction. Although NMS is most commonly
      induced by the high-potency neuroleptics, its development has also been
      associated with the use of non-neuroleptic agents that block central dopamine
      pathways. A 68-year-old man with generalized anxiety disorder and depressive
      symptoms presented at the emergency department (ED) with high fever, tremor,
      muscle rigidity, rhabdomyolysis and altered mental status. NMS was considered to
      have been caused by the recent addition and subsequent dose increase in his
      treatment regimen of venlafaxine, a serotonin norepinephrine reuptake inhibitor.
      He was successfully treated with bromocriptine, lorazepam, and fluid hydration in
      the ED and intensive care unit.

PMID- 16440076
TI  - Successful treatment of imported cerebral malaria with artesunate-mefloquine
      combination therapy.
AB  - Treatment of cerebral malaria with intravenous quinine is frequently associated
      with life-threatening cardiotoxicity. We report a case of imported cerebral
      malaria successfully treated with artesunate-mefloquine combination therapy. The
      27-year-old woman presented with fever, sudden onset of binocular blindness and
      altered consciousness 10 days after a short stay in Indonesia. Hyperparasitemia
      with Plasmodium falciparum and P. vivax in more than 5% of red blood cells was
      demonstrated on peripheral blood smear. She was admitted to the intensive care
      unit due to shock, jaundice and acute renal failure. Because of a shortage of
      intravenous quinine, intravenous artesunate was given as an alternative. Her
      condition stabilized on the 3rd day of therapy, with resolution of fever and
      disappearance of parasitemia. Consolidation therapy with oral mefloquine and
      primaquine was then given to prevent recrudescence and relapse. The only adverse
      event associated with artesunate was transient reticulocytopenia, which resolved
      after discontinuation of therapy. Her vision completely recovered, along with
      renal and liver function.

PMID- 16440078
TI  - Learning gains derived from a high-fidelity mannequin-based simulation in the
      pediatric emergency department.
AB  - There are limited data on the effectiveness of mannequin-based simulations in
      pediatrics. This study developed a training program using a high-fidelity child
      mannequin to simulate critical cases in an emergency department, and examined the
      learning gains derived from this simulation. Eighteen pediatric residents, as
      pairs, participated in a high-fidelity simulation pretest, training session and a
      posttest. The training session, developed based on participants' pretest
      performance, included videotape review, feedback, and hands-on practice, and
      focused on the improvement of management skills for shock and tachydyspnea. The
      pre- and posttest performances were scored for task-specific technical skills and
      behaviors. The learning gains between the pre- and posttests were significant (p
      < 0.001) for task-specific technical skills (from 64 +/- 15% to 93 +/- 4%) and
      behaviors (from 65 +/- 18% to 85 +/- 12%). This study suggests that high-fidelity
      simulation can enhance learning about how to manage critical cases in the
      pediatric emergency department.

PMID- 16440081
TI  - Imaging of DNA hybridization on microscopic polypyrrole patterns using scanning
      electrochemical microscopy (SECM): the HRP bio-catalyzed oxidation of 4-chloro-1
      naphthol.
AB  - We illustrate in this paper the successful combination of the direct and feedback
      mode of scanning electrochemical microscopy (SECM) for the writing of
      oligonucleotide patterns on thin gold films alongside the imaging of DNA
      hybridization. The patterning process was achieved using the direct mode of SECM,
      where the electrical field established between the SECM tip and the gold
      interface was used to drive the local deposition of micrometre sized polypyrrole
      spots to which a 15(mer) oligonucleotide (ODN) strand was linked covalently.
      Imaging of the deposited polypyrrole-ODNs was achieved by means of the feedback
      mode of SECM using Ru(NH(3))(6)(3+) as the mediator. The detection of the
      hybridization reaction of the ODN probes with their biotinylated complementary
      strands using SECM was possible after subsequent reactions with streptavidin and
      biotinylated horseradish peroxidase (HRP). The HRP-biocatalyzed oxidation of 4
      chloro-1-naphthol (1) in the presence of H(2)O(2), and the precipitation of the
      insoluble product 4-chloro-1-naphthon (2) on the hybridized areas on the gold
      film caused a local alteration of conductivity. Such a change in conductivity was
      sensitively detected by the SECM tip and allowed imaging of DNA arrays in a fast
      and straightforward way.

PMID- 16440083
TI  - Detecting thiols in a microchip device using micromolded carbon ink electrodes
      modified with cobalt phthalocyanine.
AB  - This paper describes the fabrication and evaluation of a chemically modified
      carbon ink microelectrode to detect thiols of biological interest. The detection
      of thiols, such as homocysteine and cysteine, is necessary to monitor various
      disease states. The biological implications of these thiols generate the need for
      miniaturized detection systems that enable portable monitoring as well as
      quantitative results. In this work, we utilize a microchip device that
      incorporates a micromolded carbon ink electrode modified with cobalt
      phthalocyanine to detect thiols. Cobalt phthalocyanine (CoPC) is an
      electrocatalyst that lowers the potential needed for the oxidation of thiols. The
      CoPC/carbon ink composition was optimized for the micromolding method and the
      resulting microelectrode was characterized with microchip-based flow injection
      analysis. It was found that CoPC lowers the overpotential for thiols but, as
      compared to direct amperometric detection, a pulsed detection scheme was needed
      to constantly regenerate the electrocatalyst surface, leading to improved peak
      reproducibility and limits of detection. Using the pulsed method, cysteine
      exhibited a linear response between 10-250 microM (r(2) = 0.9991) with a limit of
      detection (S/N = 3) of 7.5 microM, while homocysteine exhibited a linear response
      between 10-500 microM (r(2) = 0.9967) with a limit of detection of 6.9 microM.
      Finally, to demonstrate the ability to measure thiols in a biological sample
      using a microchip device, the CoPC-modified microelectrode was utilized for the
      detection of cysteine in the presence of rabbit erythrocytes.

PMID- 16440082
TI  - High efficiency micellar electrokinetic chromatography of hydrophobic analytes on
      poly(dimethylsiloxane) microchips.
AB  - This paper describes a simple method for the effective and rapid separation of
      hydrophobic molecules on polydimethylsiloxane (PDMS) microfluidic devices using
      Micellar Electrokinetic Chromatography (MEKC). For these separations the addition
      of sodium dodecyl sulfate (SDS) served two critical roles - it provided a dynamic
      coating on the channel wall surfaces and formed a pseudo-stationary
      chromatographic phase. The SDS coating generated an EOF of 7.1 x 10(-4) cm(2) V(
      1) s(-1) (1.6% relative standard deviation (RSD), n = 5), and eliminated the
      absorption of Rhodamine B into the bulk PDMS. High efficiency separations of
      Rhodamine B, TAMRA (6-carboxytetramethylrhodamine, succinimidyl ester) labeled
      amino acids (AA), BODIPY FL CASE (N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza
      s-indacene-3-propionyl)cysteic acid, succinimidyl ester) labeled AA's, and
      AlexaFluor 488 labeled Escherichia coli bacterial homogenates on PDMS chips were
      performed using this method. Separations of Rhodamine B and TAMRA labeled AA's
      using 25 mM SDS, 20% acetonitrile, and 10 mM sodium tetraborate generated
      efficiencies > 100,000 plates (N) or 3.3 x 10(6) N m(-1) in <25 s with run-to-run
      migration time reproducibilities <1% RSD over 3 h. Microchips with 30 cm long
      serpentine separation channels were used to separate 17 BODIPY FL CASE labeled
      AA's yielding efficiencies of up to 837,000 plates or 3.0 x 10(6) N m(-1).
      Homogenates of E. coli yielded approximately 30 resolved peaks with separation
      efficiencies of up to 600,000 plates or 2.4 x 10(6) N m(-1) and run-to-run
      migration time reproducibilities of <1% RSD over 3 h.

PMID- 16440084
TI  - Pulsed amperometric detection with poly(dimethylsiloxane)-fabricated capillary
      electrophoresis microchips for the determination of EPA priority pollutants.
AB  - A miniaturized analytical system for separation and detection of three EPA
      priority phenolic pollutants, based on a poly(dimethylsiloxane)-fabricated
      capillary electrophoresis microchip and pulsed amperometric detection is
      described. The approach offers a rapid (less than 2 min), simultaneous
      measurement of three phenolic pollutants: phenol, 4,6-dinitro-o-cresol and
      pentachlorophenol. The highly stable response (RSD = 6.1%) observed for
      repetitive injections (n > 100) reflects the effectiveness of Au working
      electrode cleaned by pulsed amperometric detection. The effect of solution
      conditions, separation potential and detection waveform were optimized for both
      the separation and detection of phenols. Under the optimum conditions (5.0 mM
      phosphate buffer pH = 12.4, detection potential: 0.7 V, separation potential:
      1200 V, injection time: 10 s) the baseline separation of the three selected
      compounds was achieved. Limits of detection of 2.2 microM (2.8 fmol), 0.9 microM
      (1.1 fmol), and 1.3 microM (1.6 fmol) were achieved for phenol, 4,6-dinitro-o
      cresol and pentachlorophenol, respectively. A local city water sample and two
      over-the-counter sore-throat medicines were analyzed in order to demonstrate the
      capabilities of the proposed technique to face real applications.

PMID- 16440085
TI  - Towards high capacity latex-coated porous polymer monoliths as ion-exchange
      stationary phases.
AB  - The preparation of high capacity agglomerated monolithic ion-exchangers for
      capillary ion chromatography is described. Post-modification of reactive
      monoliths was investigated as an alternative to co-polymerisation of a suitable
      functional monomer with an overarching goal of increasing ion-exchange capacity.
      Direct sulfonation of poly styrene-co-divinyl benzene monoliths using
      concentrated sulfuric acid or chlorosulfonic acid was unsuccessful even for
      monoliths containing as low as 8% crosslinker. In contrast, chemical
      transformation of reactive monoliths containing glycidyl methacrylate was used to
      increase the ion-exchange capacity by up to more than thirty-fold with ion
      exchange capacities of 14-29 microequiv g(-1) achieved. Three different reactions
      were considered, including reaction with 4-hydroxybenenesulfonic acid under basic
      conditions; reaction with thiobenzoic acid followed by transformation to a
      reactive thiol and the subsequent oxidation to the sulfonic acid; and direct
      sulfonation with sodium sulfite. Of these, the reaction with sodium sulfite
      resulted in the most significant increase in the capacity and the best separation
      performance. In the isocratic mode separation efficiencies of over 13,500 plates
      m(-1) were observed (for iodate). The separation of seven inorganic anions was
      also demonstrated using a hydroxide gradient.

PMID- 16440086
TI  - Multiplexed detection of nitrate and nitrite for capillary electrophoresis with
      an automated device for high injection efficiency.
AB  - A simple automated nanoliter scale injection device which allows for reproducible
      5 nL sample injections from samples with a volume of <1 microL is successfully
      used for conventional capillary electrophoresis (CE) and Hadamard transform (HT)
      CE detection. Two standard fused silica capillaries are assembled axially through
      the device to function as an injection and a separation capillary. Sample
      solution is supplied to the injection capillary using pressure controlled with a
      solenoid valve. Buffer solution flows gravimetrically by the junction of the
      injection and separation capillaries and is also gated with a solenoid valve.
      Plugs of sample are pushed into the space between the injection and separation
      capillaries for electrokinectic injection. To evaluate the performance of the
      injection device, several optimizations are performed including the influence of
      flow rates, the injected sample volume and the control of the buffer transverse
      flow on the overall sensitivity. The system was then applied to HT-CE-UV
      detection for the signal-to-noise ratio (S/N) improvement of the nitric oxide
      (NO) metabolites, nitrite and nitrate. In addition, signal averaging was
      performed to explore the possibility of greater sensitivity enhancements compared
      to single injections.

PMID- 16440087
TI  - Selective, reversible, reagentless maltose biosensing with core-shell
      semiconducting nanoparticles.
AB  - Reagentless and reversible maltose biosensors are demonstrated using ZnS coated
      CdSe (CdSe@ZnS) nanoparticle emission intensities. This method is based on
      electron transfer quenching of unimolecular protein-CdSe@ZnS nanoparticle
      assemblies, which is provided by a protein-attached Ru(II) complex. This Ru(II)
      complex is presumed to reduce a valence band hole of the CdSe@ZnS excited state
      by tunneling through the ZnS overcoating. The Ru(II) complex mediated quenching
      of CdSe@ZnS nanoparticle emission was only decreased 1.2-fold relative to the
      CdSe nanoparticle systems. While four different Ru(II) complex attachment sites
      provided different amounts of nanoparticle emission quenching (1.20 to 1.75-fold
      decrease), all of these attachment sites yielded maltose-dependent intensity
      changes (1.1 to 1.4-fold increase upon maltose addition). Maltose dissociation
      constants for these four biosensing systems range from 250 nM to 1.0 microM,
      which are similar to the maltose-maltose binding protein dissociation constant
      that these sensors are based on. The increased fluorescence intensity was found
      to only occur in the presence of maltose. Furthermore, the ability of these
      reagentless protein-nanoparticle assemblies to perform maltose biosensing
      reversibly is demonstrated with the addition of alpha-glucosidase. Three 50
      microM maltose additions after alpha-glucosidase addition showed increases of 2.2
      microM, 600 nM, and 150 nM maltose. This result demonstrates a fluorometric
      method for examining alpha-glucosidase activity. Using maltose binding protein to
      control Ru(II) complex interactions with CdSe@ZnS nanoparticle surfaces provide a
      novel class of highly fluorescent, photostable biosensors that are selective for
      maltose.

PMID- 16440088
TI  - Nanometre-sized molecular oxygen sensors prepared from polymer stabilized
      phospholipid vesicles.
AB  - Nanometre-sized, chemically-stabilized phospholipid vesicle sensors have been
      developed for detection of dissolved molecular oxygen. Sensors were prepared by
      forming 150 nm phospholipid vesicles from 1,2-dioleoyl-sn-glycero-3
      phosphocholine (DOPC) or DOPC doped with small (<1%) mole percentages of 1,2
      dioleoyl-sn-glycero-3-phosphoethanol amine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl)
      (NBD-PE). Sensors were stabilized via cross-linking polymerization of hydrophobic
      methacrylate monomers partitioned into the hydrophobic interior of the DOPC
      bilayer. The resultant unilamellar, nanometre-sized, polymer-lipid vesicles are
      spherical, biocompatible and protect sensing components that are loaded into the
      aqueous interior of the vesicle from interfering species in the exterior
      environment. For O(2) detection, the oxygen-sensitive fluorescent dye, tris(1,10
      phenanthroline)ruthenium(II) chloride (Ru(phen)(3)) was encapsulated into the
      aqueous interior of the polymerized phospholipid vesicle. NBD-PE was introduced
      into the phospholipid bilayer of the sensor as a reference dye, allowing
      ratiometric sensors to be constructed. The resultant sensors show high
      sensitivity, excellent reversibility and excellent linearity over a physiological
      range of dissolved oxygen concentrations. These results suggest that polymerized
      phospholipid vesicle sensors can be used for monitoring intracellular O(2)
      dynamics.

PMID- 16440089
TI  - Fabrication of nanopatterned films of bovine serum albumin and staphylococcal
      protein A using latex particle lithography.
AB  - Arrays of protein nanostructures can be formed on surfaces such as mica(0001) and
      Au(111) using lithography with polystyrene latex particles. To create arrays of
      protein nanostructures, monodisperse latex spheres are mixed with the desired
      protein (e.g. BSA, protein A or IgG) and deposited onto substrates. Protein
      coated nanospheres self-assemble into organized crystalline layers when dried on
      flat surfaces. After rinsing with water, dried latex spheres are displaced to
      expose periodic arrays of uncovered circular cavities. The immobilized proteins
      remain attached to the surface and form nanopatterns over broad areas (microns)
      corresponding to the thickness of a single layer of proteins. The nanostructures
      of immobilized proteins maintain the order and periodicity of the latex scaffold.
      The morphology and diameter of the protein nanostructures are tuneable by
      selecting the ratios of protein-to-latex and the diameters of latex spheres. Well
      defined nanostructured surfaces of proteins supply a tool for fundamental
      investigations of protein binding interactions in biological systems at the
      nanoscale and have potential applications in biochip and biosensing systems.

PMID- 16440090
TI  - VideoAFM--a new tool for high speed surface analysis.
AB  - The VideoAFM provides a 1000 fold increase in image rate compared to conventional
      atomic force microscopes, giving nanometre resolution images of surfaces at a
      rate of 15 frames s(-1), which is approximately 1 million pixels s(-1). Images of
      high stiffness surfaces such as calibration grids are provided for the first
      time, and allow for a more rigorous examination of the meaning of the data
      obtained with the VideoAFM. Instrumental changes that could provide true
      topographic images are discussed. The advantages of a high speed scanning
      technique that is integrated within a conventional AFM are outlined. Particular
      emphasis is given to the capability to 'tile' images, and hence rapidly map large
      areas with nanometre resolution. It is found that the inherent increase in
      stability that comes from a high frame rate leads to the possibility of manually
      manipulating the sample while maintaining a sharp image, allowing real-time user
      interaction with the AFM. The possible application of the VideoAFM approach for
      the very rapid analysis of surface properties and, ultimately, surface chemistry
      is discussed and some possible routes are given.

PMID- 16440091
TI  - Poly(methylene green) employed as molecularly imprinted polymer matrix for
      electrochemical sensing.
AB  - This paper describes the development of a molecularly imprinted polymer (MIP) for
      theophylline that can be used for electrochemical sensing. Theophylline is a
      commonly used medication for the treatment of asthma. Due to its very narrow
      therapeutic index, it may have toxic and potentially fatal effects on the
      individual. Electrochemical detection of theophylline is difficult, because its
      molecular structure and standard reduction potential are very similar to that of
      caffeine. A new method for fabricating molecularly imprinted polymers is proposed
      utilizing methylene green. Poly(methylene green)(PMG), prepared by
      electropolymerization of an azine, methylene green, was imprinted for
      theophylline. PMG-based MIP-coated electrodes showed sensitivity towards the
      presence of the imprint molecule in solutions, as well as selectivity for the
      imprint over the interferent molecule caffeine. The PMG-based MIP-coated
      electrode described in this paper had an improved selectivity factor and
      reproducibility compared to other theophylline-imprinted MIP-coated electrodes in
      literature.

PMID- 16440092
TI  - Electrochemical oxidation of catecholamines and catechols at carbon nanotube
      electrodes.
AB  - The differences in the electrochemical oxidation of two commonly known
      catecholamines, dopamine and norepinephrine, and one catechol,
      dihydroxyphenylacetic acid (DOPAC), at three different types of carbon based
      electrodes comprising conventionally polished glassy carbon (GC), nitrogen-doped
      carbon nanotubes (N-CNTs), and non-doped CNTs were assessed. Raman microscopy and
      X-ray photoelectron spectroscopy (XPS) were employed to evaluate structural and
      compositional properties. Raman measurements indicate that N-CNT electrodes have
      ca. 2.4 times more edge plane sites over non-doped CNTs. XPS data show no
      evidence of oxygen functionalities at the surface of either CNT type. N-CNTs
      possess 4.0 at. % nitrogen as pyridinic, pyrrolic, and quaternary nitrogen
      functionalities that result in positively charged carbon surfaces in neutral and
      acidic solutions. The electrochemical behavior of the various carbon electrodes
      were investigated by cyclic voltammetry conducted in pH 5.8 acetate buffer.
      Semiintegral analysis of the voltammograms reveals a significant adsorptive
      character of dopamine and norepinephrine oxidation at N-CNT electrodes. Larger
      peak splittings, DeltaE(p), for the cyclic voltammograms of both catecholamines
      and a smaller DeltaE(p) for the cyclic voltammogram for DOPAC at N-CNT electrodes
      suggest that electrostatic interactions hinder oxidation of cationic dopamine and
      norepinephrine, but facilitate anionic DOPAC oxidation. These observations were
      supported by titrimetry of solid suspensions to determine the pH of point of zero
      charge (pH(pzc)) and estimate the number of basic sites for both CNT varieties.
      This study demonstrates that carbon purity, the presence of exposed edge plane
      sites, surface charge, and basicity of CNTs are important factors for influencing
      adsorption and enhancing the electrochemical oxidation of catecholamines and
      catechols.

PMID- 16440093
TI  - The STEP method (statistical test of equivalent pathways): application to
      pharmaceuticals.
AB  - The STEP method (Statistical Test of Equivalent Pathways), recently developed to
      determine primary and secondary fragmentation in the MS/MS of peptides and
      carbohydrates, is applied in the current study to common pharmaceutical
      antibiotics. The classification of product ions as primary or secondary is then
      utilized to construct genealogy diagrams that aid in the structural
      characterization of the product ions. Four compounds were subjected to the MS/MS
      conditions used for the STEP method, and the method was used to correctly
      identify primary and secondary ions in three of the four pharmaceuticals.
      Calculated STEP values for erythromycin did not match previously characterized
      fragmentation assignments. This provided an opportunity to explore potential
      limitations of STEP analysis. It was determined that inaccurate STEP assignments
      could result, if the starting compound is classified as "fragile", because
      fragile ions, such as erythromycin can produce abnormally low STEP ratios. While
      this finding represents a limitation of using the STEP method to determine
      whether product ions are due to primary or secondary fragmentation for fragile
      ions, it suggests the possibility of identifying the presence of "fragile ions"
      by STEP analysis.

PMID- 16440094
TI  - Site-specific amide hydrogen exchange in melittin probed by electron capture
      dissociation Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Electron capture dissociation (ECD) has been proposed to be a non-ergodic
      process, i.e. to provide backbone dissociation of gas-phase peptides faster than
      randomization of the imparted energy. One potential consequence could be that ECD
      can fragment deuterated peptides without causing hydrogen scrambling and thereby
      provide amino acid residue-specific amide hydrogen exchange rates. Such a feature
      would improve the resolution of approaches involving solution-phase amide
      hydrogen exchange combined with mass spectrometry for protein structural
      characterization. Here, we explore this hypothesis using melittin, a haemolytic
      polypeptide from bee venom, as our model system. Exchange rates in methanol
      calculated from consecutive c-type ion pairs show some correlation with previous
      NMR data: the amide hydrogens of leucine 13 and alanine 15, located at the
      unstructured kink surrounding proline 14 in the melittin structure adopted in
      methanol, appear as fast exchangers and the amide hydrogens of leucine 16 and
      lysine 23, buried within the helical regions of melittin, appear as slow
      exchangers. However, calculations based on c-type ions for other amide hydrogens
      do not correlate well with NMR data, and evidence for deuterium scrambling in ECD
      was obtained from z*-type ions.

PMID- 16440095
TI  - Matrix-assisted laser desorption/ionization Fourier transform mass spectrometry
      quantitation via in cell combination.
AB  - Herein we describe a novel method for quantitation using a Fourier transform mass
      spectrometer (FTMS) equipped with a MALDI ion source. The unique instrumental
      configuration of FTMS and its ion trapping and storing capabilities enable ion
      packets originating from two physically distinct samples to be combined in the
      ion cyclotron resonance (ICR) cell prior to detection. These features are
      exploited to combine analyte ions from two differentially labeled samples spotted
      separately and then combined in the ICR cell to generate a single mass spectrum
      containing isotopically paired peaks for quantitative comparison of relative ion
      abundances. The utility of this new quantitation via in cell combination (QUICC)
      approach is explored using peptide standards, a bovine serum albumin tryptic
      digest, and a crude neuronal tissue extract. We show that spectra acquired using
      the QUICC scheme are comparable to those obtained from premixing the isotopically
      labeled samples in solution. In addition, we show direct tissue in situ isotopic
      formaldehyde labeling of a crustacean neuroendocrine organ, thus demonstrating
      the potential application of the QUICC methodology for direct tissue quantitative
      analysis.

PMID- 16440096
TI  - 'Top-down' characterization of site-directed mutagenesis products of
      Staphylococcus aureus dihydroneopterin aldolase by multistage tandem mass
      spectrometry in a linear quadrupole ion trap.
AB  - The gas-phase fragmentation reactions of a series of site-directed mutagenesis
      products of Staphylococcus aureus dihydroneopterin aldolase have been examined by
      multistage tandem mass spectrometry (MS/MS and MS(3)) in a linear quadrupole ion
      trap in order to explore the utility of this instrumentation for routine 'top
      down' recombinant protein characterization. Following a rapid low resolution
      survey of the fragmentation behavior of the precursor ions from the wild type
      (WT) protein, selected charge states were subjected to detailed structural
      characterization by using high resolution 'zoom' and 'ultrazoom' resonance
      ejection MS/MS product ion scans. Dissociation of the [M + 18H](18+) charge state
      yielded a range of product ions from which extensive sequence information could
      be derived. In contrast, dissociation of the [M + 20H](20+) charge state resulted
      in a single dominant y(96) product ion formed by fragmentation between adjacent
      Ile/Gly residues, with only limited sequence coverage. Further extensive sequence
      information was readily obtained however, by MS(3) dissociation of this initial
      product. From the combined MS/MS and MS(3) spectra an overall sequence coverage
      of 66.9%, with fragmentation of 85 of the 127 amide bonds within the WT protein,
      was obtained. MS/MS and MS(3) of three of the four site-directed mutagenesis
      products (E29A), (Y61F) and (E81A) were found to yield essentially identical
      product ion spectra to the WT protein, indicating that these modifications had no
      significant influence on the fragmentation behavior. The specific site of
      modification could be unambiguously determined in each case by characterization
      of product ions resulting from fragmentation of amide bonds on either side of the
      mutation site. In contrast, MS/MS and MS(3) of the K107A mutant led to
      significantly different product ion spectra dominated by cleavages occurring N
      terminal to proline, which restricted the ability to localize the modification
      site to within only an 8 amino acid region of the sequence. This work highlights
      the need for further studies to characterize the charge state, sequence and
      structural dependence to the low energy collision induced dissociation reactions
      of multiply protonated intact protein ions.

PMID- 16440097
TI  - Evaluation of two-beam fluorescence cross correlation spectroscopy for
      electrophoretic analysis of protein digests.
AB  - In this report, we evaluate experimentally and through the use of simulations and
      calculations the possibility of using 2-beam fluorescence cross correlation
      spectroscopy (2BFCCS) for the multicomponent electrophoretic analysis of
      peptides. The concept described has potential as a high throughput,
      extraordinarily sensitive means of identifying proteins and accelerating proteome
      studies. We present Monte Carlo simulation methods and results using them that
      help in understanding the capabilities and limitations of 2BFCCS for protein
      identification. We have calculated the expected pH dependent mobility and
      resultant 2BFCCS fingerprint spectra for a randomly selected subset of the
      peptides present upon digestion of horse myoglobin by trypsin. We demonstrate
      experimentally the multicomponent analysis of a mixture containing a
      fluorescently labeled peptide and a free fluorophore. We also demonstrate
      experimentally the ability to measure migration rates of dilute, single
      fluorophore species over more than 2 orders of magnitude in linear velocity
      (between 4.2 mm s(-1) and 640 mm s(-1)).

PMID- 16440098
TI  - Imaging of voltage-gated alamethicin pores in a reconstituted bilayer lipid
      membrane via scanning electrochemical microscopy.
AB  - Voltage-gated biological ion channels were simulated by insertion of the
      peptaibol antibiotic alamethicin into reconstituted phosphatidylcholine bilayer
      lipid membranes (BLMs). Scanning electrochemical microscopy (SECM) was utilized
      to probe initial BLM resistivity, the insertion of alamethicin pores, and mass
      transport across the membrane. Acquired SECM images show the spatial location of
      inserted pore bundles, the verification of voltage control over the pore
      conformational state (open/closed), and variations in passive mass transport
      corresponding to different topographical areas of the BLM. SECM images were also
      used to evaluate overall BLM integrity prior to insertion as well as transport
      (flux in open state) and leakage (flux in closed state) currents following
      insertion.

PMID- 16440099
TI  - Voltammetric study of the ion-exchange binding of non-electroactive metal cations
      to DNA-modified surfaces.
AB  - We describe a simple electrochemical protocol for studying the ion-exchange
      binding of non-electroactive ions, specifically mono- and divalent metal cations
      of biological relevance (Mg(2+), Ca(2+), and K(+)), to DNA-modified surfaces.
      After incubation in a dilute solution of multiply charged transition metal
      complex (5.0 microM [Ru(NH(3))(6)]Cl(3)), gold electrodes modified with thiolate
      DNA monolayers respond to the presence of these non-electroactive metal cations
      by producing significant changes in the cyclic voltammograms (i.e., decrease of
      the integrated charge and shift of formal potential) of the surface-bound redox
      complex ([Ru(NH(3))(6)](3+)). The divalent cations (particularly Mg(2+)) can be
      detected at very low concentrations (<10 microM), while the on-set value for K(+)
      is substantially higher (50 mM). The equilibrium binding constants for Mg(2+) and
      Ca(2+) to DNA-modified surfaces were calculated.

PMID- 16440100
TI  - Factors affecting broadband acoustic emission measurements of a heterogeneous
      reaction.
AB  - Broadband acoustic emission signals were obtained by attaching a piezoelectric
      transducer, sensitive up to 750 kHz, to the external wall of a 1 L jacketed glass
      reactor. Measurements were acquired of itaconic acid particles mixing in toluene;
      the total area of the acoustic emission signal from 55-500 kHz increased when the
      particle concentration, particle size or stir rate were increased. Signals at
      frequencies above 200 kHz were less sensitive to changes in particle size than
      those at lower frequencies. From calculation of the area of the signal in the
      range 55-200 kHz as a percentage of the signal area over the range 55-500 kHz,
      for mixtures of different size ranges of itaconic acid, it was possible to obtain
      an estimate of the mean particle size of a mixture. The heterogeneous
      esterification reaction of itaconic acid and 1-butanol was monitored non
      invasively. A decrease in the overall acoustic signal area between 60 and 500 kHz
      was observed as the reaction progressed. Particle size and concentration
      information were contained in the amplitude of the acoustic emission signal,
      while the emission frequency yielded information on changes in the mean particle
      size.

PMID- 16440101
TI  - Ageing disgracefully.

PMID- 16440102
TI  - Is tele-facilitation a viable alternative to conventional faceto- face
      facilitation?

PMID- 16440103
TI  - Folic acid awareness among women of reproductive age in Cape Town.

PMID- 16440104
TI  - Discovery's 'hospital rating' collides with clinicians.

PMID- 16440105
TI  - South Africa under-prioritises osteoporosis.

PMID- 16440106
TI  - Initiation of pre-hospital thrombolysis in South Africa.

PMID- 16440107
TI  - Intracranial endoscopy.

PMID- 16440108
TI  - When thunder roars -- go indoors!

PMID- 16440109
TI  - Professor Edmund Biernacki (1866 - 1911) and the discovery of the erythrocyte
      sedimentation rate.

PMID- 16440110
TI  - Emergency medicine -- a new era in South African medicine.

PMID- 16440111
TI  - Addressing authorship disputes.

PMID- 16440112
TI  - Cervical lymph node biopsy -- watch the nerves!

PMID- 16440113
TI  - The Cape Triage Score -- a triage system for South Africa.
AB  - The Cape Triage Score (CTS) has been derived by the Cape Triage Group (CTG) for
      use in emergency units throughout South Africa. It can also be used in the pre
      hospital setting, although it is not designed for mass casualty situations. The
      CTS comprises a physiologically based scoring system and a list of
      discriminators, designed to triage patients into one of five priority groups for
      medical attention. Three versions have been developed, for adults, children and
      infants.

PMID- 16440114
TI  - Evaluation of the buffering capacity of powdered cow's, goat's and soy milk and
      non-prescription antacids in the treatment of non-ulcer dyspepsia.
AB  - BACKGROUND: Non-ulcer dyspepsia (NUD) is the term most commonly used to describe
      a heterogeneous and often ill-defined group of dyspepsia patients whose symptoms
      of upper abdominal pain, discomfort or nausea persist in the absence of
      identifiable cause. Treatment choice commonly includes over the counter medicines
      and home remedies, e.g. milk. OBJECTIVE: To determine the relative buffering
      capacity of goat's, cow's and soy milk, non-prescription antacid drugs and
      combinations thereof. METHODS: The buffering capacities of 25 ml aliquots of each
      of the powdered milk products, the antacids alone and the combination of antacid
      and milk were determined. Statistical analysis was used to determine any
      significant differences in buffering capacity. RESULTS: When the antacids were
      examined alone, significant differences in buffering capacity were observed. When
      powdered milk products were examined alone, cow's milk had a significantly higher
      buffering capacity than either goat's or soy milk. There was no significant
      difference between goat's and soy milk. In the combination of cow's milk with
      each of the antacids, brand A and B had a similar buffering capacity,
      significantly higher than that observed with brand C. CONCLUSIONS: The
      combination with best observed buffering capacity was brand A with cow's milk,
      and the weakest buffering capacity was observed with brand C with soy milk. The
      results obtained can be attributed to the chemical constituents of the antacids
      and the milk products.

PMID- 16440115
TI  - Adrenocortical function in hospitalised patients with active pulmonary
      tuberculosis receiving a rifampicin-based regimen -- a pilot study.
AB  - OBJECTIVE: To assess whether adrenocortical function was compromised in patients
      with active tuberculosis (TB) during the first 5 days of therapy with either a
      rifampicin-based or ciprofloxacin-based regimen. DESIGN: Patients were randomised
      into two groups of 10 each. Adrenocortical function was compared in both groups
      by the measurement of biochemical indices, electrolytes, osmolality and pituitary
      adrenocortical hormones. Adrenal reserve was assessed by intravenous 250 mug
      adrenocorticotropin hormone (ACTH) stimulation tests. SETTING: Department of
      Medicine, Johannesburg Hospital. SUBJECTS: Twenty hospitalised patients who were
      diagnosed with TB. OUTCOME MEASURES: Respiratory rate, pulse rate and blood
      pressure were recorded, and urinary sodium and osmolality were measured. Serum
      ACTH, cortisol, dehydroepiandrosterone- sulphate (DHEA-S) and aldosterone were
      assayed. RESULTS: None of the patients demonstrated biochemical evidence of overt
      adrenal insufficiency. There were no significant differences between the two
      groups before or during therapy for any biochemical indices, electrolytes,
      hormones or calculated osmolality. Mean basal cortisol concentrations were
      substantially elevated and DHEA-S levels were consistently subnormal, resulting
      in a high cortisol/ DHEA-S ratio. In the ciprofloxacin group, cortisol responses
      to ACTH stimulation on day 1 were not significantly lower than on day 5. In the
      rifampicin group, cortisol concentrations decreased at each time point on day 5
      compared with day 1 (p = 0.001). However, a significantly higher mean incremental
      rise from the basal cortisol concentration was measured on day 5 at 60 minutes (p
      = 0.04). In the entire cohort of 20 patients, 40% demonstrated an incremental
      cortisol rise of < 250 nmol/l after ACTH stimulation on day 1. CONCLUSIONS:
      Rifampicin did not additionally impair adrenocortical function during the initial
      period of therapy. The high cortisol/DHEA-S ratio might be of clinical relevance.

PMID- 16440116
TI  - Prevalence of exercise-induced bronchospasm in Thokoza schoolchildren.
AB  - BACKGROUND: Asthma is a common childhood illness, with a prevalence of 1 in 10
      children. Exercise-induced bronchospasm (EIB) is a common feature of asthma and
      is found more often in children than in adults. OBJECTIVE: To determine the
      prevalence and potential impact of various factors on the prevalence of EIB in
      Thokoza schoolchildren. METHODS: Data were collected on respiratory health and
      the home environment of children living in Thokoza, Gauteng. A total of 475 9-
      and 10-year-old children performed the free-running asthma screening test
      (FRAST). An abnormal response to FRAST was defined as a reduction in the post
      exercise peak flow of more than 15% of the pre-exercise value, at 3- and 10-
      minute intervals. All children who had a fall in post-exercise flow rate (PEFR)
      of more than 15% on 2 occasions after FRAST were classified as having EIB.
      RESULTS: Using the above criteria to diagnose EIB, an overall prevalence rate of
      7.26% (95% confidence interval (CI): 4.5 - 10.3%) was recorded. A less rigorous
      definition of EIB is a fall in PEFR of more than 10% on 2 occasions after FRAST,
      and if this was used then the prevalence of EIB was 15.69% (95% CI: 10.6 -
      20.8%). Difficulty breathing and a tight chest were the most prevalent
      respiratory symptoms in children with EIB (odds ratio (OR): 1.79, 95% CI: 0.49 -
      6.49 and OR 1.69, 95% CI: 0.72 - 3.99, respectively). The use of gas and
      electricity as domestic fuels was the strongest risk factor associated with EIB,
      as shown by logistical regression analysis using an adjusted OR in a reduced
      model (OR 2.44, 95% CI: 0.71 - 8.44 and OR 2.33, 95% CI: 0.59 - 9.24,
      respectively). CONCLUSION: The prevalence of EIB reported in this study is higher
      than that reported in studies from other African countries, with the exception of
      a study from Kenya. Findings of the present study suggest that there may be a
      trend towards increasing prevalence of EIB in South African urban areas.

PMID- 16440117
TI  - Avian influenza--a pandemic waiting to happen?
AB  - Cross-species transmission of a highly pathogenic subtype of influenza A virus
      directly from birds to humans has raised many concerns. The radical methods of
      immune evasion and the possibility of human-to-human transmission as a result of
      gene reassortment between the human and avian viral subtypes pose an imminent
      threat of a global pandemic. The growing reservoir of circulating influenza among
      the bird population and the perpetuating human demographic factors promote the
      emergence of a novel viral strain. This article discusses current methods of
      identifying and treating the illness in individuals, and outlines principles of
      public health measures for preventing and containing an influenza pandemic.

PMID- 16440118
TI  - Simultaneous increases in immune-competent cells and nitric oxide in the spleen
      during Plasmodium berghei infection in mice.
AB  - BACKGROUND AND PURPOSE: Nitric oxide and other reactive nitrogen intermediates
      (RNI) are thought to be important mediators of both immunological and
      pathological responses of the vertebrate host to malaria infection. The role of
      RNI has been studied most often by assay of stable RNI metabolites (nitrites,
      nitrates) in blood. This study evaluated the nature of the RNI response of mice
      to malaria by analyzing the subsets of immune-competent cells within the organ
      displaying increased RNI in vivo. METHODS: We measured RNI production indirectly,
      as stable metabolites of nitric oxide activity in tissue homogenates (brain,
      liver, spleen) from mice infected with Plasmodium berghei. Only spleen exhibited
      an RNI concentration response during rising parasitemia. Subsets of immune
      competent cells (B cells, CD19+), macrophages/monocytes (MOMA2+) and T cells
      (CD4+, CD8+) in the spleen were assayed by fluorescence activated cell scan flow
      cytometry. RESULTS: The spleen was confirmed as a major source of RNI during mid
      phase P. berghei infection. Significant increases in CD19+ and MOMA2+ spleen
      cells were evident during the mid-phase of P. berghei infection in MF1 mice when
      RNI are maximally elevated. CONCLUSIONS: The time courses of the cellular and RNI
      responses indicate that CD19+ and MOMA2+ cells may be responsible for the
      increase in RNI in the spleen. However, experiments in vitro are needed to make a
      definitive identification of the cell type(s) responsible for the increase in RNI
      in the mouse spleen during P. berghei infection.

PMID- 16440119
TI  - Identification of two gene loci involved in poly-beta-hydroxybutyrate production
      in Rhodobacter sphaeroides FJ1.
AB  - BACKGROUND AND PURPOSE: Polyhydroxyalkanoates (PHAs), biopolyesters of hydroxyl
      fatty acids, are synthesized and deposited as cytoplasmic inclusions in many
      bacteria. We isolated a poly-beta-hydroxybutyrate (PHB)-producing bacterium
      designated Rhodobacter sphaeroides FJ1. To characterize PHB biosynthesis in this
      organism, we isolated the genes encoding proteins involved in PHB metabolism.
      METHODS: The genes responsible for the synthesis, accumulation, and degradation
      of PHB in R. sphaeroides FJ1 were cloned and characterized. RESULTS: Genes
      involved in the biosynthesis and metabolism of PHB were found to be located in 2
      different loci in the genome of R. sphaeroides FJ1. One locus contained genes
      encoding PHB depolymerase (phbZ), PHB synthase (phbC), phasin (phbP) and the
      regulator protein (phbR). The other locus contained the beta-ketothiolase gene
      (phbA) and the acetoactyl-CoA reductase gene (phbB). The phbZ gene was orientated
      in an opposite direction to that of phbC, phbP and phbR genes that were located
      in the same cluster. R. sphaeroides FJ1 was able to grow in wastewater released
      from the human waste treatment plant of Fu-Jen University. Optimal growth and PHB
      production were achieved when R. sphaeroides FJ1 was grown in tryptic soy broth
      containing 50% wastewater. PHB production by R. sphaeroides FJ1 varied in media
      with different carbon to nitrogen ratios, but the level of PHB synthase was
      constant, suggesting that PHB production depends mainly on substrate supply.
      CONCLUSIONS: Six genes encoding proteins related to PHB metabolism are clustered
      in 2 separate loci, phbZCPR and phbAB, in a PHB-producing bacterium R.
      sphaeroides FJ1 isolated from wastewater. PHB synthase, the key enzyme for PHB
      synthesis, is constitutively expressed, and its expression level is not affected
      by different growth conditions.

PMID- 16440120
TI  - The significance of a rapid cold hemagglutination test for detecting mycoplasma
      infections in children with asthma exacerbation.
AB  - BACKGROUND AND PURPOSE: Mycoplasma pneumoniae infection is a frequent cause of
      community-acquired respiratory infections in children and adults. However,
      standardized, rapid, specific methods for its diagnosis are lacking. The
      relationship between M. pneumoniae infection and asthma exacerbation has been
      recently discussed in the literature. We investigated the accuracy of rapid
      detection of mycoplasma infection by cold hemagglutination test compared to
      conventional enzyme immunoassays. The clinical characteristics of mycoplasma
      infection seen during emergent visits in asthmatic children were reviewed.
      METHODS: We retrospectively reviewed medical records of patients with asthma
      exacerbation visiting the Department of Pediatric Emergency, National Taiwan
      University Hospital, over a 12-month period. Subjects 2-18 years of age diagnosed
      with asthma at our outpatient clinic were included in this study. Patients with
      immunodeficiency, congenital anomalies, neurological diseases and irregular
      follow-up were excluded. RESULTS: A total of 269 children (174 males and 95
      females) with a mean (+/- standard deviation) age of 6.15 +/- 3.08 years were
      included. The prevalence of asthma exacerbation in regular follow-up patients was
      13.4%, and as many as 19.6% of cases (74/378 person-times) required
      hospitalization. Asthma attacks were most prevalent during December. 126 patients
      had both rapid cold hemagglutination testing and mycoplasma immunoglobulin M
      titers determined using acute blood samples drawn in the emergency room; 46
      (36.5%) of these patients demonstrated mycoplasma infection. Sensitivity and
      specificity of the rapid cold hemagglutination test was 78.3% and 41.3%,
      respectively. The positive predictive value was 43.4%. Comparison of patients
      with or without mycoplasma infection revealed no differences in gender, age,
      chest X-ray findings, and most symptoms/signs and laboratory data, except that
      more signs of fever and auscultatory rales were seen in the non-mycoplasma
      infection group. CONCLUSIONS: Mycoplasma infections could be an exacerbating
      factor for asthma, and the rapid cold hemagglutination test should not be a
      guideline for prescribing macrolides in the emergency room.

PMID- 16440121
TI  - Comparison of the effects of nebulized terbutaline with or without intravenous
      betamethasone on exhaled nitric oxide in children with acute asthma attack.
AB  - BACKGROUND AND PURPOSE: Exhaled nitric oxide (eNO), a non-invasive marker that
      reflects the degree of airway inflammation, may be useful for assessing the
      response to anti-inflammatory treatment of asthma. The purpose of this randomized
      prospective study was to compare the effect of a nebulized terbutaline plus a
      single intravenous dose of betamethasone at baseline followed by a second of
      terbutaline at 6 h with the effect of the same protocol of nebulized terbutaline
      alone on airway inflammation of acute asthmatic children as demonstrated by eNO
      levels. METHODS: Children visiting the emergency department due to acute asthma
      attack were recruited. All enrolled patients had fluorescent assay-proven
      hypersensitivity to Dermatophagoides pteronyssinus. Patients were randomized to
      receive either nebulized terbutaline plus intravenous betamethasone (experimental
      group, n = 11) or nebulized terbutaline alone (control group, n = 11) at baseline
      followed by a second dose of nebulized terbutaline alone 6 h later. RESULTS:
      Exhaled NO concentrations were significantly reduced in the experimental group at
      7 h (40.25 +/- 12.43 vs 28.88 +/- 18.02 ppb; p = 0.005) and 12 h (40.25 +/- 12.43
      vs 30.11 +/- 18.16 ppb; p = 0.007) after treatment. The eNO level in the
      experimental group was also reduced at 7 h (28.88 +/- 18.02 vs 38.12 +/- 16.50
      ppb; p = 0.034) and 12 h (30.11 +/- 18.16 vs 39.36 +/- 17.63 ppb; p = 0.035)
      compared to the control group. The change of eNO concentration was correlated to
      the change of peak expiratory flow rate (PEFR) [r = -0.678; p = 0.022] and
      pulmonary index scores (r = 0.606; p = 0.048) at 7 h after treatment in the
      betamethasone group. CONCLUSION: Nebulized terbutaline given at baseline and 6 h
      later was significantly more effective in improving PEFR and asthmatic symptoms
      (pulmonary index scores) for at least 12 h when the initial dose was administered
      in combination with intravenous betamethasone.

PMID- 16440122
TI  - Diagnostic value of the Binax NOW assay for identifying a pneumococcal etiology
      in patients with respiratory tract infection.
AB  - BACKGROUND AND PURPOSE: Streptococcus pneumoniae is a common pathogen in
      respiratory tract infections which is usually underestimated with conventional
      tests, largely due to the fragility of the bacteria. This study assessed the
      diagnostic value of a rapid test (Binax NOW) for the detection of the
      pneumococcal antigen in urine. METHODS: Unconcentrated urine samples from 1243
      adults and 91 children hospitalized with respiratory tract infections were
      tested. RESULTS: In all adults with respiratory tract infections, the diagnostic
      results were as follows: sensitivity, 29 (60%) of 48; specificity, 748 (92.2%) of
      811; negative predictive value, 748 (97.5%) of 767; false-positive rate, 63 (68%)
      of 92. The diagnostic results were similar in adults with lower respiratory tract
      infections: sensitivity, 21 (64%) of 33; specificity, 658 (92.2%) of 714;
      negative predictive value, 658 (98.2%) of 670; false-positive rate, 56 (73%) of
      77. In children with respiratory tract infections, the diagnostic results were:
      sensitivity, 4 of 4; specificity 18 (64%) of 28; negative predictive value, 18 of
      18; false-positive rate, 10 of 14. The low specificity of the test in children
      may be due to frequent pneumococcal nasopharyngeal colonization. CONCLUSIONS:
      High negative predictive values and high false-positive rates were found in both
      adults and children, indicating that a negative result may be more useful than a
      positive one in clinical practice. The high specificity of this test in adults
      indicates its potential value in the choice of initial antibiotic treatment by
      eliminating pneumococcal infection as a likely cause of respiratory tract
      infection in a proportion of patients.

PMID- 16440123
TI  - Clinical and laboratory features in the early stage of severe acute respiratory
      syndrome.
AB  - BACKGROUND AND PURPOSE: To characterize the clinical and laboratory features of
      severe acute respiratory syndrome (SARS) in the early stage and to compare them
      with those of patients initially suspected of having SARS who were later
      determined to have other febrile diseases. METHODS: Between March and June 2003,
      122 patients with possible SARS were admitted to the isolation ward of Tri
      Service General Hospital. SARS was diagnosed according to the modified World
      Health Organization case definition (May 1, 2003). Among them, 43 were classified
      as probable SARS cases and a SARS etiology was excluded in 32 patients. RESULTS:
      Presenting symptoms on admission included fever (97.7% of probable cases, 84.4%
      of excluded cases), chills (39.5% vs 18.8%), cough with sputum production (16.3%
      vs 40.6%), dry cough (23.3% vs 9.4%), dyspnea (18.6% vs 9.4%), diarrhea (14.0% vs
      none), rhinorrhea (2.3% vs none), and myalgia (7.0% vs 6.6%). Common laboratory
      features included lymphopenia and elevated aspartate aminotransferase, alanine
      aminotransferase, lactate dehydrogenase, C-reactive protein and creatine kinase
      values. Intubation and mechanical ventilation were required in 12 probable cases
      and 6 excluded cases. Five patients with probable SARS (11.6%) died. A scoring
      system which was developed to differentiate SARS patients from other febrile
      patients in the emergency room could differentiate probable cases from excluded
      cases with a sensitivity of 36.4% and a specificity of 70.6%. CONCLUSIONS: The
      clinical presentation and laboratory features at the early stage do not allow
      differentiation of patients with SARS-CoV infection from other febrile patients.
      Thus, it is mandatory for all healthcare workers to strictly follow standard
      isolation precautions during an outbreak to minimize disease transmission.

PMID- 16440124
TI  - Survey of pertussis in patients with prolonged cough.
AB  - BACKGROUND AND PURPOSE: Pertussis is an acute respiratory tract illness resulting
      from Bordetella pertussis. Widespread use of pertussis vaccine over the past 50
      years has decreased the incidence of pertussis. The incidence of pertussis in
      adolescents and adults has increased in many areas of the world. This study aimed
      to evaluate the etiologic role of B. pertussis in patients with prolonged cough
      in Taiwan. METHODS: Patients with cough lasting for more than 1 week were
      recruited. Nasopharyngeal swabs were taken for culture of B. pertussis and
      detection of nucleic acid of B. pertussis by polymerase chain reaction. Serum
      samples were collected in a subset of patients for assay of immunoglobulin G and
      immunoglobulin A antibodies against pertussis toxin. RESULTS: In total, 111
      patients were recruited. Thirty-three patients agreed to have their serum samples
      taken and tested. Eight patients had evidence of acute infection with B.
      pertussis; among them, 1 was diagnosed by polymerase chain reaction and 7 by
      serology. Older subjects were more likely to suffer from pertussis than younger
      subjects. The incidence of pertussis in patients with prolonged cough was 7.2%.
      However, the rate could have been as high as 21% in those with serum samples
      tested. CONCLUSIONS: We conclude that pertussis is a prevalent disease in Taiwan,
      especially in adolescents and adults.

PMID- 16440125
TI  - In vitro activities of 16 antimicrobial agents against clinical isolates of
      extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella
      pneumoniae in two regional hospitals in Taiwan.
AB  - BACKGROUND AND PURPOSE: Infections due to extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC and ESBL-KP) have
      become an important clinical problem. Local knowledge of antimicrobial
      susceptibilities of these organisms is important for implementation of effective
      hospital anti-infective policies. METHODS: We analyzed the activities of various
      antimicrobial agents against recent isolates of ESBL-EC and ESBL-KP from 2
      regional hospitals using the agar dilution method to determine minimal inhibitory
      concentrations (MICs). A total of 80 strains of ESBL-EC and 101 strains of ESBL
      KP collected during 2003 and 2004 were included in the study. RESULTS: The MICs
      of all carbapenems were relatively low, with almost all isolates being
      susceptible. In contrast, only 30.0% of ESBL-EC and 36.6% of ESBL-KP were
      susceptible to ciprofloxacin. Flomoxef and cefmetazole were the most active
      cephamycins (88.8% and 90.0% ESBL-EC and 93.1% and 87.1% ESBL-KP susceptible,
      respectively), followed by ceftibuten (85.0% and 80.2%) and cefoxitin (42.5% and
      49.5%). A cefepime MIC < or = 8 mg/L was found in 77.5% of ESBL-EC and 73.3% of
      ESBL-KP isolates. The susceptible rates to amikacin and isepamicin were both
      81.3% for ESBL-EC; 72.3% and 73.3% for ESBL-KP. Inter-hospital differences in
      susceptibilities were demonstrated for several antimicrobials. CONCLUSIONS: The
      inter-hospital variation of these data emphasizes the need for monitoring of
      antimicrobial susceptibility profiles at the individual hospital level and to
      establish rationales supporting policy for treating infections caused by ESBL
      producing bacteria.

PMID- 16440126
TI  - Clinical characteristics and risk factors for attributable mortality in
      Enterobacter cloacae bacteremia.
AB  - BACKGROUND AND PURPOSE: Enterobacter spp. have emerged as an important cause of
      nosocomial bacteremia. The purpose of this study was to delineate the clinical,
      laboratory and microbiologic features that may influence prognosis of
      Enterobacter cloacae and enable a stratification of those patients at high risk
      of mortality. METHODS: This retrospective study reviewed 108 episodes of E.
      cloacae bacteremia occurring over a 2-year period (November 2001 to October 2003)
      at Taipei Veterans General Hospital. Univariate analysis were performed to
      demonstrate the relation of possible risk factors to death attributable to E.
      cloacae bacteremia. RESULTS: Ninety-three episodes (86.1%) were hospital
      acquired. The most common portal of entry was the genitourinary tract (17.9%)
      followed by the gastrointestinal tract (15.1%). Underlying diseases associated
      with E. cloacae bacteremia were neoplastic diseases (42 episodes, 38.9%),
      diabetes mellitus (20 episodes, 18.5%) and chronic renal failure (18 episodes,
      16.7%). The overall mortality rate was 42.6%, and E. cloacae bacteremia
      attributable mortality occurred in 22 patients (20.9%). Factors significantly
      correlated with death attributable to bacteremia were older age, a higher medium
      number of underlying diseases, hemoglobin <10 g/dL, serum C-reactive protein >10
      mg/dL, hypoalbuminemia, disseminated intravascular coagulation, septic shock,
      respiratory failure, renal failure (creatinine >2 mg/dL) and delayed clinical
      response after initiation of antibiotic therapy. CONCLUSIONS: Antibiotic
      resistant isolates and appropriate empirical antibiotic use were not independent
      predictors of mortality in this study. The condition of patients at onset of
      symptoms and presence of underlying diseases appear to be important predictors
      mortality from E. cloacae bacteremia.

PMID- 16440127
TI  - Disseminated invasive aspergillosis in an apparently immunocompetent host.
AB  - Aspergillosis is a spectrum of diseases caused by members of the genus
      Aspergillus that continues to pose a significant threat to immunocompromised,
      organ transplant, neutropenic and cancer patients. In view of increasing risk
      factors leading to invasive aspergillosis, it is imperative for clinicians to be
      familiar with the clinical presentation, diagnostic methods and management of the
      disease. We describe a 34-year-old immunocompetent male patient receiving
      chemotherapy for Aspergillus fumigatus infection that had disseminated to lung,
      liver and spleen. A computed tomogram of thorax and abdomen showed thick-walled
      cavities of different sizes with air fluid levels, consolidation in both lungs
      and involvement of liver and spleen. His broncheoalveolar lavage and sputum
      specimens yielded A. fumigatus. Successful treatment of this infection was
      achieved with amphotericin B and itraconazole.

PMID- 16440128
TI  - Painless massive ascites and hypoalbuminemia as the major manifestations of
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is frequently associated with ascites, but
      rarely without proteinuria. We report a 10-year-old girl with distended, non
      tender abdomen with shifting dullness and no pitting edema in the lower legs
      before admission. Facial rash had appeared 1-2 weeks before admission and became
      more prominent 3 days prior to admission. Hypoalbuminemia with hypertriglycemia
      (but no proteinuria or diarrhea) was noticed. The antinuclear antibody titer was
      1:2560 (speckle type) and the anti-double-stranded DNA was 1:160. Abdominal echo
      revealed no cirrhosis change or venous obstruction. Chest X-ray and
      electrocardiogram revealed no cardiomegaly or pericardial effusion. The serum
      prealbumin was low on admission day 5, but the liver function tests were within
      normal range. We deduced that the hypoalbuminemia in SLE without nephritis may be
      secondary to mesenteric vascular leakage. SLE may present with initial
      manifestation of painless massive ascites. Careful utilization of history taking,
      chest X-ray, electrocardiogram, cardiac and abdominal echo, urinary analysis and
      serum prealbumin is helpful in decision-making while assessing such patients.

PMID- 16440129
TI  - Acellular extracellular matrix for inguinal hernia repair.
AB  - To investigate the clinical safety and effectiveness of acellular extracellular
      matrix (AEM) for inguinal hernia repair, 53 well-conducted and well-chosen
      sequential cases with inguinal hernia (56 inguinal hernias) were included in our
      multi-center study. All the inguinal hernias were repaired using conventional
      tension-free surgical procedures after being classified with Gilbert methods. No
      rejection was observed after operation. All the incisions healed well and no
      recurrence was found at the sixth month follow-up. At the seventh month after
      operation, one case of recurrence of right-side bilateral inguinal hernia (type
      IV) and another case of recurrence of left-side inguinal hernia (type V) were
      found. No other recurrence was observed at the 18th month follow-up. The AEM
      material has good histocompatibility and biomechanics characters and can be used
      for inguinal hernia repair. We observed no infection, chronic pain,
      funiculotesticular reaction, local nodular or feeling of discomfort after
      operation. But a further study of the usage of AEM in the repair of type IV and V
      inguinal hernias is still needed.

PMID- 16440130
TI  - Surgical repair of recurrent hiatal hernia.
AB  - The surgical management results of recurrent hiatal hernia repair are unknown in
      the laparoscopic era. The experience of the senior authors (CJF) and (SKM) is
      reported herein. From 1993 to 2004, 52 patients underwent re-operative hiatal
      hernia surgery at our center. Preoperative symptoms were heartburn, chest pain,
      dysphagia, regurgitation and pulmonary manifestations of gastroesophageal reflux
      disease. Patients had preoperative evaluation by upper endoscopy, pH-monitoring,
      esophagogram and manometry to assess the mechanism of failure. Pre- and
      postoperative symptoms were assessed utilizing a standardized questionnaire.
      Patients underwent laparoscopic repair (n=18), open laparotomy (n=6) and
      transthoracic surgery (n=28). Ninety-five percent follow-up was achieved with a
      mean follow-up of 34 months. Thirty-seven percent of patients encountered para
      operative complications one of them died due to respiratory insufficiency. Five
      patients experienced a re-recurrent hernia. The symptom resolution was 65% for
      dysphagia, 68% for heartburn, 95% for chest pain and 79% for regurgitation. The
      overall patient satisfaction was 6.94 on a scale of 1-10. There was no
      significant difference in patient outcome when comparing the operative approaches
      or disease process. Surgical repair of recurrent hiatal hernias is safe and
      effective. Laparoscopic surgery is an appropriate alternative approach for
      recurrent hiatal hernia repair in selected patients.

PMID- 16440131
TI  - Coronary angiographic findings in asymptomatic systemic sclerosis.
AB  - The objective of this study was to assess coronary arterial involvement in
      asymptomatic systemic sclerosis (SSc) patients. Fourteen female patients with SSc
      (five limited and nine diffuse) were recruited for this study. All patients
      fulfilled the following 1980 American College of Rheumatology criteria for
      classification of SSc Masi et al (Arthritis Rheum 23:581-590 1980). None of them
      had chest pain nor electrocardiogram (ECG) changes suggestive of myocardial
      ischemia. All patients underwent thorough history taking, full clinical
      examination, routine laboratory investigations, and basic screening for
      conventional atherosclerotic disease risk factors. ECG and coronary
      catheterization were done for all patients. We detected 19 coronary angiographic
      abnormalities in our cohort. Three out of nine diffuse SSc patients (33.33%) had
      ectasia of the coronary arteries, and all of them had slow flow but none in the
      limited type. One patient with limited SSc showed spasm. Three out of five
      patients with limited type (60%) had stenosis, one of them had uncontrolled
      hypertension, while none of the diffuse type had. Five patients (55.55%) of the
      diffuse type had tortuosity, while it was found in only two patients (40%) of the
      limited type. Three patients (33.3%) of the diffuse type had calcification of the
      coronaries, while it was seen in two patients (40%) of the limited type.
      Pathological involvement of coronary arteries in asymptomatic SSc patients is not
      uncommon but not paralleled by clinical symptomatology.

PMID- 16440132
TI  - Intrafamilial phenotypic diversity in multiple epiphyseal dysplasia associated
      with a COL9A2 mutation (EDM2).
AB  - We describe a Japanese family with an autosomal dominant multiple epiphyseal
      dysplasia (MED EDM2) showing significant phenotypic diversity among the five
      affected members. Genomic analysis for COL9A2 identified an Ex3-1A>G heterozygous
      mutation, which has been proved to result in skipping of exon 3. The proband was
      a 9-year-old boy, who presented with ulnar club hands due to severe epiphyseal
      dysplasia in the distal ulnae. Radiological examination showed multiple
      epiphyseal dysplasias, predominantly involving the knee and the wrist. The hip
      appeared almost normal. The malalignment of the wrist was successfully treated
      with a limb lengthening procedure. The phenotype of the asymptomatic 12-year-old
      brother was similar to, but milder than, that of the proband. The asymptomatic 39
      year-old mother, the 35-year-old uncle, and the 65-year-old grandmother with
      bilateral painful knees showed radiographically mild and severe osteoarthritis of
      the knee, respectively, and none of them had wrist deformity.

PMID- 16440133
TI  - Endocarditis associated with antineutrophil cytoplasmic antibodies: a case report
      and review of the literature.
AB  - We report a case of subacute bacterial endocarditis associated with small vessel
      vasculitis and a strongly positive cytoplasmic antineutrophil cytoplasmic
      antibody (c-ANCA) test. It is important to recognize this cause of positive c
      ANCA because infectious endocarditis may closely mimic the clinical
      manifestations of ANCA-associated vasculitides such as Wegener granulomatosis or
      microscopic polyangiitis. Furthermore, ANCA-associated vasculitis may result in
      noninfectious endocarditis, which may be confused with bacterial endocarditis. In
      this paper, we review reported cases of ANCA-positive bacterial endocarditis and
      compare them to the reported cases of ANCA-associated idiopathic vasculitis with
      endocardial compromise.

PMID- 16440134
TI  - Improvement of lung function in patients with systemic sclerosis after 6 months
      cyclophosphamide pulse therapy.
AB  - This study aims to analyze the effects of cyclophosphamide pulse therapy on
      parameters of lung function in patients with systemic sclerosis. Nineteen
      patients with systemic sclerosis (15 women and four men, aged 25-67 years, mean
      disease duration 5 years and 9 months) were included in this study. The main
      reason for the beginning of cyclophosphamide therapy was the decrease of transfer
      factor (DLCO) or diffusing coefficient for carbon monoxide (DLCO/VA) under 70% of
      predictive value. Intravenous cyclophosphamide was administered monthly in a dose
      of 500 mg/m(2 )body surface. The efficacy was evaluated by comparison of forced
      vital capacity (FVC), DLCO, and DLCO/VA at the baseline and 1 month after the
      sixth pulse. Statistical analyses were performed using Student's T test and
      Wilcoxon's test. The difference between FVC at the baseline (86.6%) and at the
      end of the follow-up period (89.2%) was not statistically significant (t=-1.25,
      p>0.05). However, a significant increase of DLCO (from 61.2% to 70.5%, z=-2.04,
      p=0.04) and DLCO/VA (from 57.8% to 72.5%, z=-2.67, p=0.008) was observed. Minor
      side effects were noticed in some patients. Two patients had nausea after
      cyclophosphamide infusion, two patients had insignificant decrease of creatinine
      clearance, and two patients had temporary and mild leukopenia. In patients with
      systemic sclerosis and lung involvement, an improvement of lung-diffusing
      capacity was noticed 6 months after the beginning of cyclophosphamide pulse
      therapy, with only minor side effects.

PMID- 16440135
TI  - Anakinra in mutation-negative CINCA syndrome.

PMID- 16440136
TI  - Juvenile rheumatoid arthritis manifesting in only limping due to flexion
      contraction of the knee.
AB  - Juvenile rheumatoid arthritis (JRA) is a relatively uncommon condition. The
      damage to the cartilaginous tissue is often irreversible and responsible for much
      of the morbidity. Timely diagnosis and appropriate aggressive treatment of
      patients improve quality of life and outcome. A reported case of JRA is presented
      in which limping associated with flexion contraction of the knee developed
      without any systemic symptoms. Magnetic resonance imaging and arthroscopic
      examination were helpful with early diagnosis. Aspirin was effective. There have
      been no recurrence to date.

PMID- 16440138
TI  - A review of perinatal acute pain: treating perinatal pain to reduce adult chronic
      pain.
AB  - Changes in neural connections and activity after an acute insult are hypothesised
      to contribute to chronic pain syndromes in mature experimental animals and
      humans. Over the last decade, studies have suggested that exposure to repeated
      painful procedures during the early perinatal period results in profound changes
      in sensitivity of nociceptive pathways. Both animal and human studies show that
      early pain experiences increase pain responses beyond the period of infancy.
      These data suggest a need to increase implementation of guidelines for minimising
      pain exposures during infancy. In addition, an experimental perinatal pain model
      may provide a unique opportunity to study the effects on the nervous system of
      both painful insults and pre-emptive analgesia.

PMID- 16440137
TI  - ADP and ATP binding to noncatalytic sites of thiol-modulated chloroplast ATP
      synthase.
AB  - A modified 'cold chase' technique was used to study tight [(14)C]ADP and
      [(14)C]ATP binding to noncatalytic sites of chloroplast ATP synthase (CF(0)F(1)).
      The binding was very low in the dark and sharply increased with light intensity.
      Dissociation of labeled nucleotides incorporated into noncatalytic sites of
      CF(0)F(1 )or CF(1) reconstituted with EDTA-treated thylakoid membranes was also
      found to be light-dependent. Time dependence of nucleotide dissociation is
      described by the first order equation with a k (d) of about 5 min(-1). The
      exposure of thylakoid membranes to 0.7-24.8 muM nucleotides leads to filling of
      up to two noncatalytic sites of CF(0)F(1). The sites differ in their specificity:
      one preferentially binds ADP, whereas the other - ATP. A much higher ATP/ADP
      ratio of nucleotides bound at noncatalytic sites of isolated CF(1) dramatically
      decreases upon its reconstitution with EDTA-treated thylakoid membranes. It is
      suggested that the decrease is caused by conformational changes in one of the
      alpha subunits induced by its interaction with the delta subunit and/or subunit I
      II when CF(1) becomes bound to a thylakoid membrane.

PMID- 16440139
TI  - Value of postmarketing surveillance studies in achieving a complete picture of
      antimigraine agents: using almotriptan as an example.
AB  - Randomised controlled trials cannot collect all the data relevant for use in
      everyday clinical practice because drug exposure is limited, endpoints are
      restricted and some patient populations are excluded. Postmarketing surveillance
      (PS) studies can add important information for real-world clinical practice.
      Acute migraine therapy with almotriptan 12.5 mg was evaluated in 4 PS studies, 2
      conducted in Spain, 1 in Germany and 1 in France. Almotriptan was associated with
      a high rate of treatment response and was well tolerated in all 4 studies. In the
      Spanish and German studies, 2-hour pain-relief, 2-hour pain-free, and sustained
      painfree rates were enhanced when patients treated mild pain. Patient
      satisfaction with almotriptan, assessed in the German and French studies, was
      high and the majority of patients preferred almotriptan to their previous acute
      migraine therapy. In conclusion, PS studies augment our knowledge of antimigraine
      therapy, giving a more complete picture of how such agents work in the general
      population.

PMID- 16440140
TI  - Reliability of pain threshold measurement in young adults.
AB  - The objective was to examine reliability of pressure and thermal (cold) pain
      threshold assessment in persons less than 25 years of age, using intra-class
      correlation (ICC) and coefficients of repeatability and variability. We measured
      thresholds to pain from pressure algometry and ice placed at the hand and head in
      10 healthy volunteers aged 18-25. Intra-rater reliability was examined with ICC.
      Coefficients of repeatability (CR) and variability (CV) were estimated.
      Reliability of repeat assessments was high as assessed by ICC, although
      coefficients of repeatability and variation indicated considerable inter
      individual variation in repeat measurements. Pressure algometry and strategically
      placed ice appear to be reliable techniques for assessing pain processing in
      young adults. Reliability studies employing ICC may benefit from complementary
      estimation of CR and CV.

PMID- 16440141
TI  - Feasibility and safety of thrombectomy with TVAC aspiration catheter system for
      patients with acute myocardial infarction.
AB  - Early reperfusion with angioplasty and stenting is established as a central,
      effective treatment for acute myocardial infarction (AMI). The role of
      thrombectomy prior to angioplasty remains to be elucidated. To evaluate its
      feasibility, safety, and efficacy, thrombectomy using a TVAC aspiration catheter
      system was attempted prior to angioplasty and stenting in 40 consecutive patients
      with AMI. Fifty consecutive patients with AMI in whom angioplasty and stenting
      were performed without prior thrombectomy served as controls. Neither
      distribution of Killip classification nor culprit lesion was different between
      the two groups. In patients treated with the TVAC system, the procedure was
      successful in 39/40 patients (98%) and there were no procedure-related
      complications. In the final coronary angiogram, TIMI-3 (Thrombolysis in
      Myocardial Infarction) flow was obtained in 37/40 (93%) in patients treated with
      the TVAC system and 43/50 (86%) in control patients. Electrocardiograms before
      and after coronary intervention were analyzed in patients with ST elevation AMI
      (35 patients treated with the TVAC system and 41 control patients). ST elevation
      recovery >50% of the initial value was observed after coronary intervention in
      26/35 (74%) in patients treated with the TVAC system and 26/41 (63%) in control
      patients (P = 0.33). In the case of anterior AMI, ST elevation recovery >50% of
      the initial value was observed in 13/17 (76%) in patients treated with the TVAC
      system and 8/20 (40%) in control patients (P = 0.045). Thus, thrombectomy using a
      TVAC system is feasible, safe, and may have the potential to enhance ST-segment
      resolution in patients with anterior AMI.

PMID- 16440142
TI  - The effect of VVI pacing on P-wave dispersion in patients with dual-chamber
      pacemakers.
AB  - The incidence of atrial fibrillation is higher in patients with VVI pacing mode
      than DDD pacing mode, but the likely mechanism is not clearly understood. We
      aimed to evaluate whether short-term VVI pacing increases inhomogeneous atrial
      conduction by using P-wave dispersion. Forty-seven patients (32 men, 15 women,
      mean age 54 +/- 13 years) with DDD pacemakers were enrolled in this study. Twelve
      lead surface ECGs were obtained in all patients during VDD pacing after an
      observation period of 1 week. The mode was then changed to VVI and 12 lead
      surface ECGs were obtained after another 1-week observation period. P-wave
      durations were calculated in all 12 leads in both VDD and VVI pacing modes. The
      difference between the maximum and the minimum P-wave duration was defined as the
      P-wave dispersion (PWD = P(max) - P(min)). P-wave maximum duration (P(max))
      calculated in VVI pacing mode was significantly longer than in VDD pacing mode
      (128 +/- 19 vs 113 +/- 16 ms, P < 0.001). There was no significant difference in
      the P-wave minimum durations (80 +/- 13 ms vs 79 +/- 12 ms, P = 0.7) between VVI
      pacing and VDD pacing. The P-wave dispersion value was higher in the VVI pacing
      mode than in the VDD pacing mode (48 +/- 8 ms vs 34 +/- 7 ms, P < 0.001). Short
      term VVI pacing induces prolongation of P(max) and results in increased P-wave
      dispersion, which might be responsible for the development of atrial fibrillation
      more frequently in these patients than in those with the VDD pacing mode.

PMID- 16440143
TI  - Early diastolic mitral annular velocity and color M-mode flow propagation
      velocity in the evaluation of left ventricular diastolic function in patients
      with Fabry disease.
AB  - Fabry disease is an X-linked genetic disorder characterized by progressive
      intracellular accumulation of neutral glycosphingolipids. Cardiac involvement is
      frequent and left ventricular (LV) diastolic dysfunction is present in most of
      the affected subjects. Pulsed-wave tissue Doppler echocardiography (PW-TDE) and
      color M-mode are new Doppler methods for LV diastolic function evaluation. Their
      role in the assessment of Fabry disease-related cardiomyopathy remains to be
      established. In this study we aimed to determine the utility of PW-TDE and color
      M-mode-derived parameters in the assessment of LV diastolic function in patients
      with Fabry disease. Eighty-one echocardiographic examinations performed in 35
      patients affected by Fabry disease were retrospectively analyzed. Early diastolic
      lateral mitral annular velocity (E(m)) determined by PW-TDE and color M-mode flow
      propagation velocity (V(p)) were measured and compared to LV filling patterns
      obtained using standard Doppler indexes. The receiver operating characteristics
      (ROC) curves method was used to determine the summary measure of relative
      accuracy for E(m) and V(p). A comparison of ROC curves showed a significant
      difference for areas under the curve in favor of E(m) (P < 0.001). Pseudonormal
      filling pattern, higher LV mass index, higher relative wall thickness, larger
      left atrial diameter, and older age were more frequent (all P < 0.001) in
      patients with incorrect diagnosis of normal LV diastolic function based on the
      measurement of V(p). E(m) appears to be superior to V(p) in the assessment of LV
      diastolic function in patients with Fabry disease. V(p) fails to detect abnormal
      LV diastolic function in subjects with pronounced concentric LV remodeling and
      pseudonormal filling pattern.

PMID- 16440144
TI  - Mitral valve surgery simultaneous to coronary revascularization in patients with
      end-stage ischemic cardiomyopathy.
AB  - Mitral valve regurgitation (MVR), occurring as a result of myocardial ischemia
      and global left ventricular (LV) dysfunction, predicts a poor outcome in terms of
      survival and morbidity. Between 1995 and 2003, 180 consecutive patients with
      impaired LV function and chronic ischemic MVR underwent cardiac surgery. Fifty
      four patients (group I), MVR (grade III-IV) underwent simultaneous MV surgery and
      coronary artery bypass grafting (CABG); 40 patients (group II), MVR (grade II
      III), and 86 patients (group III), MVR (grade I-II), underwent CABG alone. In
      group I, MV repair was performed in 36 patients (group IA) and MV replacement in
      18 (group IB). The incidence of hospital death was similar between groups. The
      actuarial event-free survival was significantly lower in group than in groups II
      and III (P = 0.0045) and I (P = 0.038). The overall actuarial survival was
      significantly higher in group IA than in group IB (P = 0.027). Postoperatively,
      the LV ejection fraction (P < 0.001), LV end-diastolic diameter (P < 0.001), LV
      end-systolic diameter (P < 0.01), and cardiac index (P < 0.001) improved
      significantly in group I. The regurgitation fraction decreased significantly in
      Groups I and III after surgery (P < 0.001 and P = 0.003, respectively). Both MV
      repair and replacement that preserves subvalvular apparatus in patients with end
      stage ischemic myocardiopathy offer an acceptable outcome. Mitral valve repair
      simultaneous to CABG improves significantly the LV function and its geometry. In
      patients with mild to moderate mitral regurgitation, CABG alone may be performed
      with good overall survival, but with lower event-free survival than those
      undergoing concomitant mitral valve repair.

PMID- 16440145
TI  - Mitral valve annuloplasty and myocardial revascularization in the treatment of
      ischemic dilated cardiomyopathy.
AB  - The aim of this study was to examine perioperative mortality and morbidity and
      midterm results in patients undergoing coronary bypass graft and mitral valve
      annuloplasty with advanced dilated cardiomyopathy. Sixty-one patients with
      ischemic dilated cardiomyopathy underwent coronary artery bypass grafting and
      mitral valve annuloplasty between January 1998 and December 2003. Patients
      eligible for revascularization that presented a mild or more severe mitral valve
      regurgitation at echocardiography (effective regurgitant orifice > 0.2 cm(2))
      were considered for annuloplasty with a Cosgrove ring. New York Heart Association
      class (NYHA) III/IV was present in 40 patients (66%) and Canadian Cardiovascular
      Society class III-IV in 19 (31%). A previous acute myocardial infarction was
      reported in 48 patients (79%). The mean number of graft anastomoses was 2.5 +/-
      0.7 and the left internal mammary artery was used in 49 patients (80%). In
      hospital mortality was 4.9% (3 patients), due to unsuccessful weaning from
      cardiopulmonary bypass, multiple organ failure, and stroke, respectively. Left
      ventricle ejection fraction improved from 28.9% +/- 5.2% preoperatively to 35.4%
      +/- 8.1% at follow-up (P = 0.0001) and a significant reduction in NYHA III/IV was
      detected: from 40 patients preoperatively (66%) to 14 (31%) at follow-up (P =
      0.031). Midterm cardiac-related mortality rate was 3.4%. In our experience
      combined coronary artery bypass grafting and ring annuloplasty for ischemic
      dilated cardiomyopathy can be performed with acceptable risks for in-hospital
      mortality and morbidity. Midterm results show a good survival rate and a durable
      functional improvement in this subset of patients.

PMID- 16440146
TI  - Effect of N-acetylcysteine on oxidative stress and ventricular function in
      patients with myocardial infarction.
AB  - Recent evidence suggests that postischemic myocardial dysfunction ("stunning")
      may be mediated by oxygen free radicals. Various studies have reported the
      beneficial effects of antioxidants in ischemia-reperfusion injury. The aim of
      this study was to assess the effect of N-acetylcysteine (NAC) treatment on
      oxidative stress, infarct size, and left ventricular (LV) function, as adjunct
      therapy in myocardial infarction (MI). Patients with acute MI received either 15
      g NAC infused over 24 h (n = 15) or no NAC (n = 15), combined with streptokinase.
      Peripheral venous blood was serially sampled to measure creatine kinase (CK)-MB
      levels. Plasma malondialdehyde (MDA) level was measured at admission and after 4
      and 24 h. Echocardiography was performed within 3 days of MI and after 3 months.
      At admission, plasma MDA levels were not different between the groups. In the NAC
      treated patients plasma MDA levels decreased, whereas in the nontreated NAC
      patients MDA levels increased at 4 and 24 h (P < 0.01 and P < 0.001,
      respectively). Left ventricular ejection fraction was higher (P < 0.05) and LV
      end-systolic and end-diastolic diameters were lower (P < 0.001 and P < 0.001) in
      patients receiving NAC on day 3. Left ventricular wall motion score index was
      significantly lower in patients treated with NAC on day 3 (P < 0.05). Left
      ventricular diastolic parameters were not different whether patients were treated
      with NAC or not. No difference in reduction of infarct size was detected between
      the groups according to CK-MB levels. It was thus demonstrated that
      administration of NAC in combination with streptokinase significantly diminished
      oxidative stress and improved LV function in patients with acute MI. These
      encouraging results would justify the performance of a larger controlled study.

PMID- 16440147
TI  - Aortic elastic properties in young pregnant women.
AB  - This study aimed to investigate the aortic elastic properties of young pregnant
      women by comparing them with those of age-matched healthy females. The study
      group consisted of 21 pregnant women at a mean age of 26 +/- 1 years; 22 healthy
      women at a mean age of 25 +/- 1 years constituted the control group. Doppler
      color echocardiographic variables and serum estradiol (E2) levels were measured
      from both groups. The blood samples were obtained from the control group in the
      first week after menstrual bleeding. Diastolic and systolic blood pressure (DBP
      and SBP, respectively) were measured with a sphygmomanometer. Systolic and
      diastolic aortic diameters (AOS and AOD, respectively) were measured 3 cm
      proximal to the aortic valves. Aortic elastic properties were assessed according
      to the following formulas: 1, Aortic strain = (AOS - AOD)/AOD; 2, Aortic
      distensibility = 2 x (AOS - AOD)/(PP x AOD); 3, Aortic diameter change = AOS -
      AOD; 4, Aortic stiffness index = ln(SBP/DBP)/(AOS - AOD)/AOD. The results were
      expressed as mean +/- standard deviation and compared by t-test between groups. P
      < 0.05 was considered as statistically significant. All women in the study group
      were in their first pregnancy and second trimester. The height and weight were
      160 +/- 5 vs 164 +/- 6 cm and 60 +/- 9 vs 54 +/- 3 kg in the study vs control
      groups, respectively (P < 0.05). The AOD was 26 +/- 3 vs 26 +/- 4 mm and AOS 29
      +/- 3 vs 28 +/- 4 mm. Pulse pressure was 43 +/- 3 vs 45 +/- 8 mmHg in the study
      vs control groups, respectively (P > 0.05). The serum E2 level was significantly
      higher in pregnant women (21 300 +/- 2 300 pg/ml). Derived aortic elastic
      properties in pregnant women were also increased significantly (P < 0.0005). The
      indexes of aortic elastic properties are altered and aortic stiffness is
      decreased among young pregnant women. This may be due to the adaptation
      mechanisms including high estradiol levels detected in pregnancy.

PMID- 16440148
TI  - Effects of N-acetylcysteine on myocardial ischemia-reperfusion injury in bypass
      surgery.
AB  - Myocardial ischemia-reperfusion injury may complicate coronary artery bypass
      grafting (CABG) operations. N-Acetylcysteine (NAC) had antioxidant and
      microcirculatory effects, and inhibits neutrophil aggregation. The aim of this
      study was to determine the effects of NAC in limiting myocardial ischemia
      reperfusion injury in CABG operations. Twenty patients undergoing elective
      coronary bypass operation with cardiopulmonary bypass were enrolled and randomly
      assigned to two groups: a control group operated with a routine CABG protocol,
      and one where NAC was administered intravenously during the operation (NAC
      group). Blood samples from coronary sinus for tumor necrosis factor-alpha assay,
      myocardial biopsy specimens for chemiluminescent luminol, and lucigenin
      measurements of reactive oxygen species were taken. The luminol (specific for
      (*)OH, H(2)O(2), and HOCl(-) radicals) and lucigenin (specific for O(2) (*-))
      levels and the difference ratios after reperfusion were significantly lower in
      the NAC group. Tumor necrosis factor-alpha levels increased in the control group
      but, in contrast, a significant decrease was detected in the NAC group (P <
      0.01). Creatine kinase-MB levels at 6 and 12 hours were significantly lower in
      the NAC group (P = 0.02). N-Acetylcysteine has potential effects to limit
      ischemia reperfusion injury during CABG operations. We believe that its effects
      on clinical outcome may be more apparent in patients prone to ischemia
      reperfusion injury.

PMID- 16440149
TI  - Effect of pressure overload and its recovery on the rat carotid artery: change of
      vascular reactivity and remodeling process.
AB  - Compared to chronic hypertension, little is known about the pathophysiology of
      acute hypertension and its recovery. To characterize this, we investigated the
      functional and structural properties of the common carotid arteries (CCA) from 35
      rats. We established a unilateral and reversible carotid arterial hypertension
      model using the partial transverse aortic constriction (TAC) technique. By TAC,
      the right CCAs were made to endure a pressure-overload environment, while the
      left CCAs remained under normotension. The TACs were removed 2 weeks later, which
      unloaded the hypertensive effects. We compared the contractile, histological, and
      molecular responses of the CCA before TAC, during TAC (the hypertension period),
      and after removal of TAC (the recovery period). Vessel contractility was nearly
      abolished during 2 weeks of TAC. The recovery process from hypertension showed an
      initial hypercontractile period within a week. The relaxation response due to
      acetylcholine, as measured during the recovery period, showed a longer time
      course than the contractility for recovering its magnitude. During the
      hypertension period, the media thickness increased and this persisted throughout
      the recovery period. Apoptosis of the endothelial layer was significantly
      increased during the hypertension period and this disappeared 2 weeks after
      recovery. Expression of endothelial NO synthase was not detectable at the end of
      the hypertension period, but this gradually returned to the basal level after 2
      weeks of recovery. Although increased contractility is usually expected in
      chronic hypertensive vessels, an abrupt pressure overload decreases contractility
      and the endothelium-dependent relaxation. It also increases endothelial apoptosis
      and the media thickness. These findings have clinical relevance, and they could
      be applied to human acute and severe hypertension and its recovery.

PMID- 16440150
TI  - Primary cardiac osteosarcoma in a pregnant woman.
AB  - Primary cardiac osteosarcomas are uncommon tumors. Their growth pattern is
      aggressive and the prognosis is poor. A 34-year-old, 7-month pregnant woman with
      a primary cardiac osteosarcoma associated with the anterior mitral leaflet and
      connected to the interatrial septum, causing nearly subtotal obstruction of the
      mitral valve, presented with a clinical picture of heart failure. Transthoracic
      echocardiography demonstrated an abnormal mass located in the mitral anterior
      leaflet, prolapsing into the left ventricle. Radical resection of the mass and
      replacement of the mitral valve were performed under cardiopulmonary bypass.
      Histopathology showed a low-grade osteosarcoma. The postoperative course was
      uneventful, and the patient was discharged on the 16th day after surgery. She
      gave birth after 2 months to a healthy baby after the successful operation. She
      and her baby did not have any problem during 3 months of follow-up.

PMID- 16440151
TI  - Postinfarction cardiac rupture despite immediate reperfusion therapy in a patient
      with severe aortic valve stenosis.
AB  - A 74-year-old woman with severe aortic valve stenosis (AS) was admitted to our
      hospital because of dyspnea on exertion. On day 2, she developed acute anterior
      wall myocardial infarction (MI) with ST elevation. Tissue plasminogen activator
      (tPA) was administered 10 min after the onset of chest pain, and emergency
      percutaneous coronary intervention was performed to induce coronary reperfusion
      after another 50 min. Five hours after MI onset, however, she suddenly went into
      electromechanical dissociation and died from cardiac rupture. This is the first
      case report of postinfarct cardiac rupture with severe AS occurring in spite of
      instituting immediate reperfusion therapy. High intraventricular pressure may be
      a critical risk factor for cardiac rupture in patients with AS complicated with
      acute MI. Further studies are required to clarify the risk and benefit of tPA
      administration before percutaneous coronary intervention and the necessity of the
      emergency correction of AS to prevent cardiac rupture.

PMID- 16440152
TI  - Metastasizing testicular germ-cell tumor with infiltration of the right heart:
      indication for primary metastasectomy.
AB  - Cardiac intracavitary metastases are very uncommon. The case of a 42-year-old
      male patient with a testicular germ cell tumor extending into the superior caval
      vein, the left brachiocephalic vein, and the right heart, which manifested as a
      mild form of pulmonary embolization, is presented. Due to the perceived high risk
      of continuous embolization and the urgent need to begin systemic chemotherapy, a
      complete cardiac tumor resection was performed, utilizing a cardiopulmonary
      bypass, followed by a simultaneous orchiectomy. Histology revealed a 61-cm long
      vascular tumor as a metastasis of a yolk sac tumor originating from the left
      testis. There were no postoperative complications, and the patient is alive and
      without tumor recurrence 12 months after four cycles of systemic chemotherapy
      according to the PEB (cisplatin, etoposide, bleomycin) scheme. We conclude that
      in this special case aggressive surgical management following chemotherapy was
      very effective in controlling the disseminated testicular tumor.

PMID- 16440153
TI  - An example that presented giant aneurysm of the angina pectoris after
      percutaneous coronary intervention.
AB  - We present the case of a 70-year-old woman who was admitted to our hospital with
      heart failure due to a giant left ventricular aneurysm involving the apex and
      severe mitral regurgitation. Three months before the hospitalization,
      percutaneous coronary intervention was performed for severe stenosis of the left
      main trunk. During the procedure, there were no abnormalities of distal coronary
      flow due to problems like embolization, and repeat coronary angiography,
      performed after stabilization of heart failure, showed no new significant
      stenosis. We diagnosed her condition as a subepicardial aneurysm by pathological
      examination of the resected specimen.

PMID- 16440154
TI  - Questionnaire on perioperative antibiotic therapy in 2003: postoperative
      prophylaxis.
AB  - We distributed a questionnaire to institutions accredited by the Japan Surgical
      Society asking about the use of antibiotics in digestive tract surgery in Japan
      in 2003, and compared the results with those of a similar questionnaire
      distributed in 1993. The period of antibiotic administration for esophageal
      resection was at least 6 days in 64.9% of the 1993 questionnaire responses, but
      less than 4 days in 60.4% of the present questionnaire responses. For distal
      gastrectomy, antibiotics were given for 5 days postoperatively at 53.0% of the
      responding institutions in the 1993 survey, but for only 3 days, at 72.4%, in the
      present survey. An oral antibiotic was given as part of antibacterial colon
      preparation before colon resection at 70% or more of the institutions in the 1993
      survey, while no antibiotic colon preparation was given at 80% of the
      institutions in the present survey. The period of antibiotic administration for
      laparoscopic cholecystectomy was at least 4 days in 72% of the institutions in
      the 1993 survey, but this decreased remarkably to fewer than 2 days at 80.8% of
      the institutions in the current survey. There were no differences in the
      selection of antibiotics between the two surveys. The period of antibiotic
      administration has decreased remarkably in the last decade.

PMID- 16440155
TI  - Surgical site infection in general and thoracic surgery: surveillance of 2 663
      cases in a Japanese teaching hospital.
AB  - PURPOSE: We conducted a prospective survey of 2 663 surgical patients in a
      Japanese teaching hospital to look for any risk factors predisposing to surgical
      site infection (SSI) other than the National Nosocomial Infection Surveillance
      (NNIS) System risk indices; namely, performance status, operative time, wound
      classification, and endoscopic use. METHODS: Our Infection Control Team recorded
      data for 5 years using the Japanese SSI surveillance system. We divided the
      incidence of SSI for each risk index category by the NNIS reference data to
      produce the standardized infection ratio (SIR). RESULTS: The representative
      procedure, SSI rate, and SIR in the 2663 patients were as follows: colectomy,
      6.0%, 0.917; esophagectomy, 19.4%, 6.020; mastectomy, 0.5%, 0.401; rectal
      surgery, 8.7%, 1.136; thoracic surgery, 1.5%, 1.137; and biliary surgery, 13.4%,
      1.937. We also found age to be a significant risk factor. CONCLUSIONS: The NNIS
      system risk indices should separate rectal surgery from colorectal surgery, and
      separate esophagectomy from other gastrointestinal surgery. Age should also be
      included as an SSI risk index.

PMID- 16440156
TI  - Evaluation of tap water for surgical handwashing.
AB  - PURPOSE: In Japan, sterile water is used for rinsing in surgical handwashing,
      whereas in Western countries tap water is generally used. We conducted this study
      to examine the conditions and the equipment that affect bacterial contamination
      in tap water and to determine whether the tap water in our institute is suitable
      for surgical handwashing. METHODS: First, we examined the water pipes and
      measured the free chlorine content in the tap water in the operating room. Next,
      we recruited 40 volunteers and conducted preliminary tests with sterile water.
      Thirty of these subjects participated in a handwashing test using tap water.
      RESULTS: The mean free chlorine levels in the tap water and the sterile water
      were 0.30 +/- 0.05 and 0.07 +/- 0.03 mg/l, respectively. The handwashing test
      using tap water showed immediate, persistent, and cumulative bacteria activity
      within the minimum limits set by the Food and Drug Administration (FDA).
      CONCLUSION: The free chlorine levels in the tap water in our institute satisfied
      Japanese health regulations. Moreover, the handwashing test met the criteria of
      the FDA. Thus, we conclude that this tap water is safe to use for rinsing in
      surgical handwashing.

PMID- 16440157
TI  - Outcome of patients surgically treated for various forms of hyperthyroidism with
      differentiated thyroid cancer: experience at an endocrine center in Italy.
AB  - PURPOSE: The incidence and aggressiveness of thyroid cancer associated with
      hyperthyroidism remains a subject of much controversy. The aim of this study was
      to analyze the frequency of coexisting hyperthyroidism and thyroid cancer, and to
      determine whether cancer becomes more aggressive with different forms of
      hyperthyroidism. METHODS: We retrospectively studied 2,449 patients assessed for
      hyperthyroidism between 1985 and 2001. All patients with a "cold" nodule on
      scintigraphy, such as those with Graves' disease and a concomitant solid nodule,
      underwent fine-needle aspiration biopsy (FNAB). Criteria for surgery were
      cytological findings indicative of malignancy, goiter with signs of tracheal or
      esophageal compression, side effects of antithyroid drug therapy, or Graves'
      disease with multiple relapses after therapy withdrawal or responsiveness to
      antithyroid drugs. RESULTS: Thyroid cancer was diagnosed more frequently in
      patients with Graves' disease (6.5%) than in those with uninodular toxic goiter
      (UTG) (4.4%) or multinodular toxic goiter (MTG) (3.9%). Lymph node involvement
      was found in 56% of the patients with Graves' disease, in 23% of those with MTG,
      and in none of those with UTG. Distant metastases were found in one patient with
      Graves' disease. CONCLUSIONS: Cancers associated with Graves' disease seems to be
      more aggressive than those associated with MTG or UTG. Thus, we suggest that
      patients with Graves' disease be carefully monitored for the detection of thyroid
      nodules. Ultrasonography seems to be the best modality to detect such nodules.

PMID- 16440158
TI  - Efficacy of a proton pump inhibitor given in the early postoperative period to
      relieve symptoms of hiatal hernia after open heart surgery.
AB  - PURPOSE: To evaluate the efficacy of a proton pump inhibitor, we retrospectively
      reviewed patients who underwent gastric fiberscopy (GFS) in the early phase after
      cardiac surgery. METHODS: The subjects were 103 patients who underwent GFS for
      poor appetite, gastric pain, heartburn, or hematemesis after cardiac surgery. We
      divided the patients into two groups: group I consisted of 49 patients who
      received an H2-receptor antagonist (ranitidine hydrochloride 300 mg/day), and
      group II consisted of 54 patients who received a proton pump inhibitor (PPI;
      sodium rabeprazole 10 mg/day) as prophylactic treatment. The incidence of upper
      gastrointestinal (GI) disease was compared in the two groups. RESULTS: Gastric
      fiberscopy confirmed that 82.5% of the patients had type I hiatal hernia. The
      incidences of gastric pain and heartburn were significantly higher in group I
      (12.2% and 83.7%) than in group II (0% and 37.0%). Moreover, gastric bleeding
      occurred in two patients from group I, one [corrected] of whom died of
      coagulopathy. The incidences of hemorrhagic gastritis, active ulcer, and reflux
      esophagitis were significantly higher in group I than in group II, at 22.4%,
      22.4%, and 24.5% vs 1.9%, 0%, and 7.4%. CONCLUSIONS: Early postcardiotomy GFS
      confirmed a high incidence of type I hiatal hernia. However, the proton pump
      inhibitor given in the early postoperative period proved more effective than the
      H2-receptor antagonist for relieving GI symptoms and preventing upper GI
      disorders after cardiac surgery.

PMID- 16440159
TI  - Intrapleural hypotonic cisplatin treatment for malignant pleural mesothelioma: in
      vitro experiments and clinical application.
AB  - PURPOSE: We studied the inhibitory effects of hypotonic cisplatin on the growth
      of malignant pleural mesothelioma (MPM) cell lines in vitro, and assessed the
      effectiveness of intraoperative intrapleural hypotonic cisplatin treatment
      combined with extrapleural pneumonectomy for patients with this tumor. METHODS:
      In the in vitro experiments, mesothelioma cell lines were exposed to various
      concentrations of cisplatin in either saline solution or distilled water for up
      to 5 min. After 48 h incubation, we calculated the inhibition of cell growth. In
      the clinical study, five patients with MPM underwent intraoperative intrapleural
      hypotonic cisplatin treatment combined with extrapleural pneumonectomy. RESULTS:
      The hypotonic cisplatin treatment inhibited cell growth at a significantly
      greater rate than the isotonic cisplatin treatment. Just 1-5 min exposure to 10
      microg/ml of hypotonic cisplatin inhibited growth by more than 80%. Clinically,
      no recurrence was found in four of the five patients after a median follow-up
      period of 27 months (range: 16-36 months), although contralateral multiple
      pulmonary metastases were found in one patient 10 months after surgery.
      CONCLUSION: Hypotonic cisplatin treatment is effective against MPM, and should be
      investigated further.

PMID- 16440160
TI  - Effect of prostaglandin E1 on ischemia-reperfusion injury during abdominal aortic
      aneurysm surgery.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) surgery subjects the lower extremities
      to ischemia and reperfusion. Although it is not extensive or prolonged, ischemia
      of the lower extremities during aortic cross-clamping is gradually and steadily
      induced. We studied the effects of prostaglandin E1 (PGE1) on ischemia
      reperfusion injury of the lower extremities during AAA repair. METHODS: During
      AAA surgery, two near-infrared spectroscopy probes were positioned on each calf
      muscle to monitor oxygen metabolism in the lower extremities. We also measured
      lactate concentration in both iliac veins. RESULTS: Near-infrared spectroscopy
      signals responded sensitively to aortic cross-clamping and declamping. Lactate
      increased time-dependently during aortic cross-clamping. The continuous venous
      administration of PGE1 (20 ng/kg per minute) inhibited the accumulation of
      lactate during aortic cross-clamping. Declamping of the first iliac artery
      resulted in a further but transient increase in ipsilateral venous lactate, which
      may be one component in the mechanism of declamping shock. Prostaglandin E1
      eliminated the transient increase in ipsilateral lactate. The administration of
      PGE1 inhibited the contralateral accumulation of lactate after first declamping,
      and the lactate level decreased gradually before the second declamping.
      CONCLUSIONS: Prostaglandin E1 seems to have a protective effect against ischemia
      reperfusion injury of the lower extremities during AAA surgery.

PMID- 16440161
TI  - Factors affecting the regression of surgically replaced abdominal aortic
      aneurysms.
AB  - PURPOSE: After endovascular therapy for abdominal aortic aneurysms, aneurysm sac
      shrinkage is considered to be the best marker of successful treatment. Such
      shrinkage, however, is infrequent and the rate of shrinkage is variable because
      of endoleaks. To investigate the factors that influence such contraction, the
      aneurysm sac regression after a conventional surgical replacement of the
      abdominal aortic aneurysm in an inclusion fashion was studied. METHODS: Abdominal
      aortic aneurysms that measured 5 cm in diameter or larger were studied in 35
      patients who underwent surgical replacement. The aneurysm sac was closed anterior
      to the prosthesis. Of the 35 cases, 4 aneurysms were inflammatory and 10 had
      aneurysm wall circumferential calcification of greater than 40%. Computed
      tomography was performed preoperatively, and at 1 week, and then 3 months
      postoperatively. RESULTS: The maximum major and minor diameters of the aneurysmal
      sac decreased significantly from 1 week to 3 months after surgery (major
      diameter: 49 +/- 12 to 32 +/- 8 mm and minor diameter: 39 +/- 10 to 26 +/- 7 mm).
      In inflammatory aneurysms, the maximum major and minor diameters were
      significantly larger at 3 months postoperatively, in comparison to nonspecific
      aneurysms. Among the 31 patients with nonspecific aneurysms, the maximum major
      diameter was significantly larger in those with aneurysmal calcification of
      greater than 40% of its circumference at 3 months postoperatively, in comparison
      to noncalcified aneurysms. CONCLUSIONS: The surgically repaired abdominal aortic
      aneurysm contraction tends to develop over 3 months, and inflammation,
      thickening, and calcification of the aneurysm wall are all considered to
      influence the regression of the aneurysm.

PMID- 16440162
TI  - Histological classification of liver fibrosis and its impact on the postoperative
      clinical course of patients with congenital dilatation of the bile duct.
AB  - PURPOSE: Infants and children with congenital dilatation of the bile duct (CDBD)
      usually also have some degree of liver fibrosis, which occasionally persists
      after diversion surgery, leading to liver cirrhosis. We conducted this study to
      evaluate the histological degree of liver fibrosis using intraoperative biopsy
      and to determine whether it affects the postoperative clinical course. METHODS:
      The subjects were 43 infants and children with CDBD. The age at operation ranged
      from 1 month to 14 years. Histological classification was defined as follows:
      grade 0, no fibrosis; grade 1, fibrosis confined to the portal area; grade 2,
      bridge formation with the neighboring portal area; grade 3, widened bridging
      fibrosis; and grade 4, pseudolobule formation, representative of cirrhosis.
      RESULTS: There were 21 (48.8%) patients with grade 0, 17 (39.5%) with grade 1, 4
      (9.3%) with grade 2, 1 (2.3%) with grade 3, and 0 (0%) with grade 4 fibrosis.
      There were no differences in preoperative serum total bilirubin, total bile acid,
      aspartate aminotransferase, or gamma-glutamyl transpeptidase levels among the
      four groups. On the other hand, the grade 2 and 3 groups tended to include
      patients with a lower age at operation, and lower amylase levels in the serum and
      bile. Postoperatively, clinical symptoms resolved and laboratory data normalized
      in all patients. Two patients underwent liver biopsy for other reasons 3 and 4
      years after surgery, which confirmed disappearance of the liver fibrosis. These
      patients had originally had grade 1 and grade 2 fibrosis, respectively.
      CONCLUSION: Mild to moderate liver fibrosis is present in almost half of all
      children with CDBD; however, if it is graded as less than moderate, it will
      probably not affect the postoperative clinical course.

PMID- 16440163
TI  - Results of regional chemotherapy using the aortic stop-flow technique in advanced
      pancreatic carcinoma.
AB  - PURPOSE: Systemic palliative chemotherapy provides only a disappointing response
      and almost no prolongation of the survival time in patients with pancreatic
      carcinoma. Isolated perfusion may lead to a higher concentration of cytostatics
      within the target tissue, which can be associated with a high response rate and
      longer survival in addition to a low rate of side effects. The aim of the study
      was to investigate the feasibility of the aortic stop-flow technique using
      commercially available tools in patients with advanced pancreatic carcinoma.
      METHODS: Seventeen patients with either unresectable or metastasized pancreatic
      carcinoma (diagnosed by histologic investigation) were enrolled in the study. In
      total, a 20-min hypoxic perfusion of the isolated abdominal compartment with 20
      mg/m2 of mitomycin C (Medac, Hamburg, Germany) was carried out 22 times. The
      cytostatic concentration was determined intrainterventionally within the systemic
      and regional compartment. The tumor response was assessed using computed
      tomography and a tumor marker (CA19-9) every 4 weeks. RESULTS: While 12 patients
      underwent one cycle, in 5 patients two complete perfusions were performed.
      Mitomycin C concentration was 10-fold higher within the regional compared with
      the systemic compartment at its maximum. The area under the curve (AUC) was 4.02
      times larger. The degree of toxicity was considerable: World Health Organization
      grade I/II in 8/17, III/IV in 9/17 cases. Three treatment-related deaths were
      documented. The objective response rate was 17.6% (3 of 17 cases; 1 complete
      remission [CR], 2 partial remissions [PR]). In 3 subjects, a stable disease (SD)
      and in 11 individuals tumor progression (PD) was registered. The median survival
      was 4.1 months. CONCLUSION: The aortic stop-flow technique was associated with a
      high toxicity rate but no improvement in the tumor response and survival was seen
      in comparison to the systemic chemotherapy of the historical group. Despite
      detectable pharmacokinetic advantages, the aortic stop-flow technique is
      therefore not considered to be feasible for palliative chemotherapy in patients
      with pancreatic carcinoma for routine use.

PMID- 16440164
TI  - Restorative proctocolectomy for pediatric patients with ulcerative colitis.
AB  - PURPOSE: A restorative proctocolectomy has become an elective surgical treatment
      for patients with ulcerative colitis (UC). In children with UC, however, the role
      of this procedure has not yet been well evaluated. We investigated the
      postoperative status of pediatric patients with UC regarding the side effects of
      steroids, postoperative complications, and growth. METHODS: The medical records
      of 15 patients with UC who underwent a restorative proctocolectomy between August
      1993 and October 2003 were retrospectively reviewed. RESULTS: Their mean age was
      12.6 +/- 3.4 years (range 5.7-15.7; boys: 9, girls: 6). All patients had total
      colitis, except for one who had left-sided colitis. The mean cumulative dose of
      preoperative prednisolone was 6201 +/- 7980 mg (mean +/- SD). The operative
      indications were an unsuccessful response to medical treatments in 12 patients
      (80%) and severe colitis in 3 patients (20%). Surgery was performed in one stage
      in 6 patients and in two stages in 9 patients. Seven patients (47%) demonstrated
      growth retardation at the time of operation. Steroid-related complications were
      seen in 3 cases, i.e., steroid myopathy, glaucoma, and cataracts, respectively.
      As early postoperative complications, an intestinal obstruction was seen in 2
      patients, peritonitis in 1, and pancreatitis in 1. As late complications,
      anastomotic stenosis was observed in 5 patients, pouchitis in 4, residual
      proctitis in 3, and anal or proctovaginal fistula in 2. An intestinal
      obstruction, peristomal pyoderma gangrenosum, and dehydration each was seen in 1
      patient. A growth "catch-up" was obtained for all but one patient. All patients
      became free of corticosteroids. CONCLUSION: A restorative proctocolectomy was
      found to be an effective treatment alternative even in children with UC when
      conservative therapy proves to be ineffective.

PMID- 16440165
TI  - The use of fibrin glue in the treatment of fistula-in-ano: a prospective study.
AB  - PURPOSE: This prospective study was done to analyze the efficacy of commercial
      fibrin glue application in the healing of patients with fistulas-in-ano. METHODS:
      This clinical trial of 36 patients was performed during the period from November
      2003 to May 2004. Thirty men and six women were treated for a fistula-in-ano with
      commercial fibrin glue application. None of the patients had undergone prior
      attempts to correct fistulas-in-ano surgically. All patients received
      preoperative mechanical bowel preparation and prophylactic intravenous
      antibiotics. In the operating room, the patients underwent an anorectal
      examination under spinal anesthesia. The external and internal fistula tract
      openings were then identified. The fistula tract was curetted. Fibrin glue was
      injected into the external fistula opening until fibrin glue could be seen coming
      from the internal opening. No dressing was applied over the external opening.
      Thereafter, the patient was discharged. A 1-week course of oral antibiotics was
      prescribed. The patients were followed up for 70 weeks with a mean of 54 weeks
      (range 40-70 weeks). RESULTS: The cause of the fistula-in-ano was cryptoglandular
      in all patients. The overall initial success rate was 77.8% (28/36). No
      complications were encountered related to the application. Two patients underwent
      a reapplication with fibrin glue and the fistulas of these patients were all
      closed. The overall success rate was 83.3% (30/36). CONCLUSION: Fibrin glue
      application was thus found to be an easy, safe, effective, and useful alternative
      treatment in the management of fistulas-in-ano. However, our findings need
      substantiation by increasing the number of patients and prolonging the follow-up
      duration, as well as carrying out comparative studies.

PMID- 16440166
TI  - Thyroid papillary carcinoma recurring as squamous cell carcinoma: report of a
      case.
AB  - We report a case of local squamous cell carcinoma recurrence of thyroid papillary
      carcinoma, 4 years after subtotal thyroidectomy, in an 82-year-old woman. The
      papillary cancer of the right thyroid was histopathologically classified as T2a,
      N0, M0, Ex1; pT2a, pN1b, pEx1; Stage III. Fine-needle aspiration cytology of the
      recurrent tumor revealed atypical squamous epithelium-like cells with
      keratinization. The tumor was judged cytologically to be class III, defined as a
      suspicious malignancy and, after reoperation, it was diagnosed
      histopathologically as papillary carcinoma recurrence with extensive squamous
      metaplasia. The recurrent papillary carcinoma was thought to have changed to a
      squamous cell carcinoma because most of the tumor was occupied by atypical
      squamous cells, with a small amount of glandular tissue. The primary tumor was
      histologically diagnosed as a well-differentiated papillary carcinoma at the
      initial operation. It contained numerous tall neoplastic cells with eosinophilic
      granules and pseudostratified nuclei, indicating that it could potentially
      transform into squamous cell carcinoma. We report this case as an example of how
      squamous cell carcinoma of the thyroid can develop.

PMID- 16440167
TI  - Omental transposition for lymphedema after a breast cancer resection: report of a
      case.
AB  - Lymphedema of the arm and hand is one of the major complications after a breast
      cancer resection. Conservative treatment for the treatment of lymphedema, such as
      compression garments and centripetal massage, is very important for these cases.
      However, if the lymphedema is difficult to control with conservative treatment
      and the patient's quality of life (QOL) is compromised due to swelling of the
      arms, surgical treatment should be considered. We used omental transposition to
      improve the status of lymphedema in the present patient whose left arm and hand
      had been swollen for 5 years, which thus prevented her from being able to lift
      her arm. After the operation, she was able to lift her left arm herself and
      perform tasks with her left hand, thereby obtaining a better QOL than before the
      operation regarding her left arm movement.

PMID- 16440168
TI  - Large chest wall reconstruction using a pedicled osteomuscle composite flap:
      report of a case.
AB  - A 67-year-old man with diabetes mellitus and chronic renal failure underwent
      resection of a grade 1 chondrosarcoma. We performed chest wall reconstruction of
      the massive defect, using a pedicled osteomuscle composite flap comprising the
      6th, 8th, and 10th ribs, and the latissimus dorsi and serratus anterior muscles.
      This flap is ready to mobilize as a pedicled graft to cover a large chest wall
      defect; it is strong enough to buttress the chest cage without the need for
      artificial materials, and it is associated with a lower risk of infection than
      prosthetic materials.

PMID- 16440170
TI  - Computed tomographic demonstration of a fish bone in abdominal actinomycosis:
      report of a case.
AB  - A 53-year-old man who had the habit of consuming fish bones was referred to our
      clinic because of a suspected malignant abdominal wall tumor. Computed tomography
      (CT) showed a mass (10 x 5 cm) in continuity with the transverse abdominal
      muscle, containing a small calcification. A laparotomy was performed with a
      preoperative diagnosis of an inflammatory mass due to fish bone penetration from
      the sigmoid colon. A fish bone, measuring 2.3 cm in length, was detected within
      the tumor by specimen radiography. The pathological findings demonstrated
      actinomycotic colonies. We herein present the first case of a CT demonstration
      showing a fish bone in an abdominal mass which was pathologically confirmed to be
      actinomycosis. Evidence of the presence of a foreign body is valuable for
      diagnosing inflammatory nodules such as actinomycosis and differentiation from
      malignancies.

PMID- 16440169
TI  - Resection of sternal metastasis from endometrial carcinoma followed by
      reconstruction with sandwiched marlex and stainless steel mesh: report of a case.
AB  - We report the successful resection of sternal metastasis from endometrial
      carcinoma, followed by reconstruction of the chest defect, in an 87-year-old
      woman. We performed subtotal sternectomy and concurrent resection of the ribs and
      overlying soft tissue. The skeletal defect was then reconstructed with sandwiched
      Marlex and stainless steel mesh, and soft tissue coverage was accomplished by
      using a pectoralis major advancement flap. The patient had an uneventful
      postoperative course with no sign of recurrence during 5 years of follow-up.
      Thus, reconstruction with Marlex and stainless steel mesh could be an effective
      technique for preventing paradoxical movement of the thorax and protecting the
      intrathoracic organs.

PMID- 16440171
TI  - Isolated superior mesenteric vein injury from blunt abdominal trauma: report of a
      case.
AB  - Solitary injury of the superior mesenteric vein (SMV) after blunt abdominal
      trauma is a rare but frequently fatal injury. A 63-year-old man was admitted to
      our hospital after falling on his right side from a height of 5 m. Computed
      tomography (CT) showed blood in the peritoneal cavity, but no liver or spleen
      injury. Emergency laparotomy revealed complete disruption of the SMV across the
      site of confluence with the splenic vein. We performed primary reconstruction by
      connecting both ends of the vein as an end-to-end anastomosis. Following
      restoration of gastrointestinal passage the patient was discharged in good
      health. At his 6-month follow-up, angio-CT showed an unobstructed SMV and portal
      vein. There was slight stenosis at the site of the suture and no sign of
      development of collateral venous circulation into the liver. This case report
      shows that primary repair of an SMV injury can be done in a stable patient
      without concomitant life-threatening injuries once proximal and distal control of
      bleeding has been achieved. Ligation should be reserved for patients with
      multiple injuries and an unstable condition.

PMID- 16440173
TI  - Easy pulmonary vein isolation using epicardial cryoablation.
AB  - The maze procedure can be accomplished by several techniques with varying degrees
      of success. These techniques include cut-and-sew, endocardial cryoablation, and
      epicardial ablation using heat-producing devices. We describe our surgical
      modification of pulmonary vein isolation with cryoablation using an epicardial
      and endocardial approach. This simple and reliable technique, which does not need
      any special device, will assist in mitral valve surgery for patients with chronic
      atrial fibrillation.

PMID- 16440172
TI  - Primitive neuroectodermal tumor arising in the colon: report of a case.
AB  - Peripheral primitive neuroectodermal tumors (pPNETs) are usually found in the
      soft tissue of the extremities, paravertebral region, and chest wall. We report a
      rare case of a pPNET arising in the colon. A 59-year-old man underwent left
      hemicolectomy for an infiltrative ulcerating tumor, 11 cm long, in the descending
      colon. Histological examination of the resected specimen revealed small, round
      cell proliferation with rosette-like structures, and confirmed regional lymph
      node involvement and peritoneal dissemination near the primary tumor.
      Immunohistochemically, the tumor cells were positive for synaptophysin and MIC2
      (CD 99). ESW-FLI1 chimeric mRNA was detected in the tumor by reverse
      transcriptase-polymerase chain reaction. The patient underwent resection of
      recurrence in the retroperitoneum 3 months later, but metastasis rapidly
      developed and he died of the disease 7 months after his first operation.

PMID- 16440174
TI  - A safer technique of aortic root replacement after aortic valve replacement.
AB  - Aortic root replacement after aortic valve replacement (AVR) is often complicated
      by bleeding around the aortic root, which increases the risk of morbidity and
      mortality, making it a technically challenging procedure. We describe a new
      technique of aortic root replacement designed to minimize bleeding around the
      aortic root. This surgical technique focuses on safe dissection and exposure of
      the aortic root to avoid inadvertent entry into the right atrium or right
      ventricle; on modifying the proximal anastomosis of the graft to the aortic
      annulus; and on performing a coronary artery reimplantation that achieves
      complete hemostasis at the suture lines. We performed aortic root replacement
      after AVR in four patients over a 4-year period, without encountering any
      bleeding around the aortic root.

PMID- 16440176
TI  - Impaired iron transport activity of ferroportin 1 in hereditary iron overload.
AB  - To investigate the functional significance of mutations in Ferroportin that cause
      hereditary iron overload, we directly measured the iron efflux activity of the
      proteins expressed in Xenopus oocytes. We found that wild type and mutant
      Ferroportin molecules (A77D, N144H, Q248H and V162Delta) were all expressed at
      the plasma membrane at similar levels. All mutations caused significant
      reductions in (59)Fe efflux compared to wild type but all retained some residual
      transport activity. A77D had the strongest effect on (59)Fe efflux (remaining
      activity 9% of wild-type control), whereas the N144H mutation retained the
      highest efflux activity (42% of control). The Q248H and V162Delta mutations were
      intermediate between these values. Co-injection of mutant and wild-type mRNAs
      revealed that the A77D and N144H mutations had a dominant negative effect on the
      function of the WT protein.

PMID- 16440177
TI  - Developmental maturation and segmental distribution of rat small intestinal L
      carnitine uptake.
AB  - Oral L-carnitine supplementation is commonly used in sports nutrition and in
      medicine; however, there is controversy regarding the mechanisms that mediate
      intestinal L-carnitine transport. We have previously reported that the Na(+)/L
      carnitine transporter OCTN2 is present in the small intestinal apical membrane.
      Herein we aimed to find out if this step of intestinal L-carnitine absorption is
      ontogenically regulated, and if so, to determine the molecular mechanism(s)
      involved. L-[(3)H]-Carnitine uptake was measured in the jejunum and ileum of
      fetuses (E17 and E21), newborn (1 day-old), suckling (15 day-old), weaning (1
      month-old) and adult (2 and 6 month-old) Wistar rats. Both, Na(+) -dependent and
      Na(+) -independent L-carnitine uptake rates, normalized to intestinal weight,
      significantly increased during the late gestation period, and then declined
      during the suckling period. After weaning, the rate of Na(+) -dependent L
      carnitine uptake is no longer measurable. In E21- fetuses and newborn rats, L
      carnitine uptake was higher in the ileum than in the jejunum. The decline in
      Na(+) -dependent L-carnitine uptake with maturation was mediated via a decrease
      in the V(max) of the uptake process with no change in its apparent K(m). Semi
      quantitative RT-PCR assays showed that OCTN2 mRNA levels were significantly
      higher in E21-fetuses and newborn rats compared to suckling rats, which were in
      turn significantly higher than that in adult rats. Neither retardation of weaning
      nor L-carnitine supplementation prevented the down-regulation of Na(+)/L
      carnitine transport activity. The results demonstrate for the first time that
      intestinal Na(+) -dependent L-carnitine uptake activity is under genetic
      regulation at the transcriptional level.

PMID- 16440178
TI  - The hormonal control of uterine luminal fluid secretion and absorption.
AB  - The secretion of uterine luminal fluid initially provides a transport and support
      medium for spermatozoa and unimplanted embryos, while the absorption of uterine
      luminal fluid in early pregnancy results in the closure of the lumen and allows
      blastocysts to establish intimate contact with the uterine epithelium. We have
      established an in vivo perfusion technique of the lumen to study the hormonal
      control of the events in the peri-implantation period. Fluorescein-labelled
      dextran was included in the perfusion medium to monitor fluid movements and the
      concentrations of Na(+) and CI(-) ions in the effluent were monitored. Using an
      established regimen of steroid treatment of ovariectomized rats mimicking early
      pregnancy, oestradiol caused fluid secretion, while progesterone resulted in an
      amiloride-sensitive fluid absorption. Fluid absorption peaked at about the
      expected time of implantation. The effect of progesterone could be inhibited by
      treatment with a high dose of oestradiol, by the anti-progestin RU486, and by the
      presence of an intra-uterine contraceptive device. Studies of expression of Na(+)
      and CI(-) channels (ENaC, CFTR) indicated that these channels were subject to
      tissue-specific regulation within the uterus, but more work is required to
      determine their role and the factors controlling their abundance and localization
      in early pregnancy.

PMID- 16440179
TI  - Escherichia coli heat stable (STa) enterotoxin and the upper small intestine:
      lack of evidence in vivo for net fluid secretion.
AB  - Heat stable (STa) enterotoxin from E. coli reduced fluid absorption in vivo in
      the perfused jejunum of the anaesthetized rat in Krebs-phosphate buffer
      containing lactate and glucose (nutrient buffer), in glucose saline and in
      glucose free saline. Bicarbonate ion enhanced fluid absorption of 98 +/- 7 (6)
      microl/cm/h was very significantly (P < 0.0001) reduced by STa to 19 +/- 4 (6)
      microl/cm/h, but net secretion was not found. When impermeant MES substituted for
      bicarbonate ion, net fluid absorption of 29 +/- 3 (6) microl/cm/h was less (P <
      0.01) than the values for phosphate buffer and bicarbonate buffer. With STa in
      MES buffer, fluid absorption of 3 +/- 2 (6) microl/cm/h was less than (P < 0.001)
      that in the absence of STa and not significantly different from zero net fluid
      absorption. E. coli STa did not cause net fluid secretion in vivo under any of
      the above circumstances. Neither bumetanide nor NPPB when co-perfused with STa
      restored the rate of fluid absorption. In experiments with zero sodium ion
      containing perfusates, STa further reduced fluid absorption modestly by 20
      microl/cm/h. Perfusion of ethyl-isopropyl-amiloride (EIPA) with STa in zero
      sodium ion buffers prevented the small increment in fluid entry into the lumen
      caused by STa, indicating that the STa effect was attributable to residual sodium
      ion and fluid uptake that zero sodium-ion perfusates did not eradicate. These
      experiments, using a technique that directly measures mass transport of fluid
      into and out of the in vivo proximal jejunum, do not support the concept that E.
      coli STa acts by stimulating a secretory response.

PMID- 16440180
TI  - Aldosterone reduces crypt colon permeability during low-sodium adaptation.
AB  - Fluid and electrolyte absorption by colonic crypts depends on the transport
      properties of crypt cellular and paracellular routes and of the pericryptal
      sheath. As a low-Na(+) diet increases aldosterone and angiotensin II secretion,
      either hormone could affect absorption. Control and adrenalectomized (ADX)
      Sprague-Dawley rats were kept at a high-NaCl (HS) diet and then switched to low
      NaCl (LS) diet for 3 days. Aldosterone or angiotensin II plasma concentrations
      were maintained using implanted osmotic mini-pumps. The extracellular Na(+)
      concentration in isolated rat distal colonic mucosa was determined by confocal
      microscopy using a low-affinity Na(+) -sensitive fluorescent dye (Sodium red, and
      Na(+) -insensitive BODIPY) bound to polystyrene beads. Crypt permeability to FITC
      labelled dextran (10 kDa) was monitored by its rate of escape from the crypt
      lumen into the pericryptal space. Mucosal ion permeability was estimated by
      transepithelial electrical resistance (TER) and amiloride-sensitive short-circuit
      current (SCC). The epithelial Na(+) channel, ENaC, was determined by
      immunolocalization. LS diet decreased crypt wall permeability to dextran by 10
      fold and doubled TER. Following ADX, aldosterone decreased crypt wall dextran
      permeability, increased TER, increased Na(+) accumulation in the pericryptal
      sheath and ENaC expression even in HS. Infusion of angiotensin II to ADX rats did
      not reverse the effects of aldosterone deprivation. These findings indicate that
      aldosterone alone is responsible for both the increase in Na(+) absorption and
      the decreased paracellular and pericryptal sheath permeability.

PMID- 16440181
TI  - Pericryptal myofibroblast growth in rat descending colon induced by low-sodium
      diets is mediated by aldosterone and not by angiotensin II.
AB  - Pericryptal myofibroblast growth in descending colonic crypts correlates with the
      activation of the renin-angiotensin-aldosterone system. Earlier work showed that
      during the transition from a high-Na(+) (HS) to low-Na(+) (LS) diet there are
      changes in the colonic crypt wall and pericryptal sheath. As LS diet increases
      both aldosterone and angiotensin II, the aim here was to determine their
      individual contributions to the trophic changes in colonic crypts. Experiments
      were conducted on control and adrenalectomized Sprague-Dawley rats fed an HS diet
      and then switched to LS diet for 3 days and supplemented with aldosterone or
      angiotensin II. The actions of the angiotensin-converting enzyme inhibitor
      captopril, the angiotensin receptor antagonist losartan and the aldosterone
      antagonist spironolactone on extracellular matrix proteins, claudin 4 and E
      cadherin myofibroblast proteins, alpha-smooth muscle actin (alpha-SMA) and OB
      cadherin (cadherin 11), angiotensin type 1 and TGFbetar1 membrane receptors were
      determined by immunolocalization in fixed distal colonic mucosa. The LS diet or
      aldosterone supplementation following ADX in HS or LS increased extracellular
      matrix, membrane receptors and myofibroblast proteins, but angiotensin alone had
      no trophic effect on alpha-SMA. These results show that aldosterone stimulates
      myofibroblast growth in the distal colon independently of dietary Na(+) intake
      and of angiotensin levels. This stimulus could be a genomic response or secondary
      to stretch of the pericryptal sheath myofibroblasts accompanying enhanced rates
      of crypt fluid absorption.

PMID- 16440182
TI  - Electrogenic H+ transport and pH gradients generated by a V-H+ -ATPase in the
      isolated perfused larval Drosophila midgut.
AB  - A method for microperfusion of isolated segments of the midgut epithelium of
      Drosophila larvae has been developed to characterize cellular transport pathways
      and membrane transporters. Stereological ultrastructural morphometry shows that
      this epithelium has unusually long tight junctions, with little or no lateral
      intercellular volume normally found in most epithelia. Amplification of the
      apical and basal aspects of the cells, by approximately 17-fold and approximately
      7-fold, respectively, predicts an almost exclusively transcellular transport
      system for solutes. This correlates with the high lumen-negative transepithelial
      potential (V(t)) of 38 to 45 mV and high resistance (R(t)) of 800 to 1,400 Omega
      x cm(2) measured by terminated cable analysis, in contrast to other microperfused
      epithelia like the renal proximal tubule. Several blockers (amiloride 10(-4) M,
      ouabain 10(-4) M, bumetanide 10(-4) M), K(+) -free solutions, or organic solutes
      such as D-glucose 10 mM or DL-alanine 0.5 mM failed to affect V(t) or R(t).
      Bafilomycin-A(1) (3 to 5 microM) decreased V(t) by approximately 40% and short
      circuit current (I(sc)) by approximately 50%, and decreased intracellular pH when
      applied from the basal side only, consistent with an inhibition of an
      electrogenic V-H(+) -ATPase located in the basal membrane. Gradients of H(+) were
      detected by pH microelectrodes close to the basal aspect of the cells or within
      the basal extracellular labyrinth. The apical membrane is more conductive than
      the basal membrane, facilitating secretion of base (presumably HCO(3)(-)), driven
      by the basal V-H(+) -ATPase.

PMID- 16440183
TI  - [Posttraumatic arthritis in the hind foot].
AB  - Posttraumatic arthritis of the joint components of the hind foot is typically
      linked with hind foot deformity and involvement of the neighbouring joint. The
      principal goals of any hind foot reconstruction are to achieve a quasi-anatomical
      reconstruction of the geometry and a stable and plantigrade foot position as a
      prerequisite for acceptable gait function, and an overall satisfactory result for
      the patient. Profound knowledge of the functions of the ankle-hind foot complex
      is the basis for the development of a valid therapeutic strategy. Any surgical
      reconstruction has to consider previous interventions, local soft tissue
      conditions, neurovascular status, and the components of deformity and degree of
      arthritic destruction at the corresponding joint levels. In general, an
      arthrodesis of any hind foot joint, as a key element in hind foot reconstruction,
      will be successful if correction of the underlying deformity is also adequately
      addressed.

PMID- 16440184
TI  - [On the problem of halo vest treatment in the elderly. Results of a retrospective
      analysis].
AB  - INTRODUCTION: The treatment of unstable cervical spine injuries with the halo
      vest represents an established procedure. So far no data reflecting the quality
      of life of patients following a halo vest treatment are available. Elderly people
      make up a large part of the inpatients in our hospital. Therefore special
      attention is payed to this group of patients in this study. METHODS: In this
      study 41 patients (average age of 51.8 +/- 23.5 years) with an unstable injury of
      the upper cervical spine were investigated. All of them underwent a halo vest
      therapy in our hospital during 1988-2003. The health-related quality of life was
      assessed in the mean 8.0 years after the trauma by using the SF-36 Health Survey.
      Additionally, the incidence of complications and the union rate over time were
      observed. RESULTS: The evaluation of the data obtained from the SF-36 revealed a
      reduced quality of life in the patient group in comparison to the reference
      population. This was particularly apparent in patients older than 60 years. The
      fracture healing under halo vest treatment was comparably slow. In 17% of the
      cases no fracture union was obtained after 12 weeks. This was only seen for
      patients older than 60 years. The complication rate associated to the halo vest
      amounted to 43% and was independent of age. CONCLUSION: The treatment of unstable
      fractures of the upper cervical spine with a halo vest results in a prolongated
      fracture healing for elderly people. Furthermore a halo vest therapy reduces the
      health related quality of life. Therefore, even for elderly patients an internal
      osteosynthetic stabilization of an unstable injury of the upper cervical spine
      should be considered if indicated.

PMID- 16440185
TI  - [Trauma centers in Germany. Status report].
AB  - BACKGROUND: In Germany, a total of more than 30,000 polytraumatized patients are
      treated in level I-IV trauma centers. The exact number of hospitals fulfilling
      the requirements for the treatment of severely injured patients is unknown. We
      analyzed the number of hospitals in Germany capable of managing polytraumatized
      patients. We further analyzed the influence of various geographic and
      infrastructure conditions on the management of severely injured patients in the
      various Federal States in Germany. METHODS: First we conducted a nationwide
      research of all hospitals specialized in trauma management. Points of interest
      were structural and personnel requirements. These data were compared to the data
      obtained by the Federal Statistical Office. With a special software program we
      were able to conduct for the first time a geographic visualization of all trauma
      hospitals. RESULTS: There are 108 level I trauma centers, 209 level II trauma
      centers, and 431 level III and IV trauma centers in Germany. The geographic
      concentration of hospitals fulfilling the requirements for the treatment of
      severely injured patients differs regionally. There is an obvious correlation
      between trauma deaths and a low hospital concentration and less developed
      infrastructure. CONCLUSION: Objectively, the number of trauma centers for the
      treatment of severely injured patients seems to be adequate in Germany.
      Nevertheless, there are substantial differences between various Federal States in
      Germany concerning the distribution of hospitals as well as the geographic and
      infrastructure conditions. To optimize trauma management in Germany we think that
      the formation of regional trauma networks is mandatory.

PMID- 16440186
TI  - [The undetected brain lesion in sports. Minor traumatic brain injury and its
      sequelae].
AB  - The minor traumatic brain injury (mTBI) in sports is often looked at as a
      bagatelle. The treating physician underestimates the severity of the injury
      suspecting that a mTBI is a nonstructural lesion with an overall excellent
      prognosis in the majority of the cases. This paper shows that the minor traumatic
      brain injury may be a structural brain lesion with potentially life-threatening
      dangers. The therapy should follow exactly defined guidelines, e.g., stepwise
      protocol of the Concussion in Sports (CIS-) Group. Return to sports activities
      should happen only when all physical but also cognitive symptoms have subsided.
      All mTBIs that have been sustained prior to the actual injury have to be recorded
      properly because repeated mTBIs may cause chronic degenerative brain damage.
      Neuropsychological testing will aid in the correct diagnosis of a mTBI and is a
      useful parameter in the course of the injury. In the future biochemical markers
      may serve as indicators of the severity of the brain injury and may also aid in
      predicting the outcome after TBI. Today biochemical markers do not serve as a
      substitute for neuroimaging.

PMID- 16440187
TI  - [Liver biopsy under guidance of multislice computed tomography: comparison of 16G
      and 18G biopsy needles].
AB  - BACKGROUND: Percutaneous cutting needle biopsy of focal liver lesions under CT
      guidance has established itself as a standard method. The purpose of this study
      was to evaluate which diagnostic quality can be achieved under guidance of
      multislice CT (MSCT) and with the use of different needle sizes. METHODS: The
      data of 163 MSCT-guided core biopsies of focal liver lesions were evaluated. A
      16G biopsy needle was used in 121 cases and an 18G needle in 42 cases. RESULTS:
      The sensitivity, specificity, and accuracy for all biopsies were 93.3, 100.0, and
      94.5%. The corresponding values were 97.2, 100.0, and 97.5% for the 16G needle
      and 78.6, 100.0, and 85.7% for the 18G needle, respectively. A definite
      histological diagnosis could be obtained in 90.0% of the cases (16G 94.0%, 18G
      75.8%). These differences were statistically highly significant. Bleeding
      complications were recognized in seven biopsies (4.3%). In one patient a fatal
      bleeding occurred after the biopsy. Median biopsy duration was 27 min.
      CONCLUSIONS: Core biopsy under MSCT guidance is a fast and very accurate method
      to obtain a histological diagnosis in focal liver lesions. The usage of a 16G
      needle in comparison to an 18G needle yielded a significantly higher rate of
      correct results with regard to differentiation between benign and malignant
      disease as well as establishing a definite histological diagnosis. For an
      accurate diagnosis of liver lesions a 16G needle is recommended. After biopsy,
      the patients have to be closely monitored.

PMID- 16440188
TI  - [MRI in staging of lung cancer].
AB  - PURPOSE: Overview of magnetic resonance imaging (MRI) in staging of lung cancer.
      MATERIAL AND METHODS: Currently available methods of imaging lung cancer, lymph
      node and distant metastases by MRI are explained. At present, MRI is mainly used
      in the detection of cerebral metastases and assessment of infiltration of the
      thoracic wall and of the mediastinum. The capabilities of T2-weighted single-shot
      TSE (HASTE) and T1-weighted 3D gradient echo techniques (VIBE) are demonstrated.
      RESULTS: With the advent of new fast sequences like HASTE and VIBE the spatial
      resolution comes close to that of computed tomography but with an outstanding
      soft tissue contrast and without radiation exposure. The introduction of lymph
      node specific contrast media will improve sensitivity and specificity in N
      staging. Additionally, whole-body MRI is capable of detecting distant metastases,
      in particular in the organs at risk, i.e. brain, upper abdomen and
      musculoskeletal system. CONCLUSION: MRI is gaining importance as part of a
      multimodal imaging approach for staging of lung cancer.

PMID- 16440189
TI  - [Acute nonspecific pain in the lower abdominal region].

PMID- 16440190
TI  - [Ectopic ureter with urinary dribbling in childhood -- a diagnostic challenge:
      our own experience and review of the literature].
AB  - Based on the observations in four girls suffering from constant urinary dribbling
      we analyzed the special features and difficulties in making the diagnosis of an
      ectopic ureter. In all patients there was marked diagnostic delay. In one
      symptomatic case the abnormality was not detected before the age of 18 years.
      Failure to recognize the characteristic signs and symptoms played a crucial role
      in delaying the diagnosis. Moreover, imaging of ureteral ectopia represents a
      diagnostic challenge. The ectopic ureters were associated with dysplastic, poorly
      functioning renal moieties. Common diagnostic imaging procedures, such as
      ultrasound, intravenous pyelography, or voiding cystourethrography yielded
      incomplete diagnostic information and often failed to provide a definitive
      diagnosis. The latter could only be obtained with MR urography. We assessed the
      diagnostic value of the different examinations and compared our findings with
      those reported in the literature.

PMID- 16440191
TI  - [Comparison of unidimensional and bidimensional measurement to assess therapeutic
      response in the treatment of solid tumors].
AB  - PURPOSE: In this prospective study we applied both the bidimensional WHO method
      and the unidimensional RECIST method in treatment follow-up of solid tumors.
      MATERIAL AND METHODS: Computed tomography was performed in 80 patients before and
      after one chemotherapy cycle: 20 patients each with lung cancer, lymphoma, and
      metastases of the lung and the liver. In 207 tumor lesions unidimensional and
      bidimensional measurements were performed: 36 lesions of lung cancer, 51 lesions
      of lymphoma, and 60 lesions of metastases of the lung and the liver,
      respectively. We assigned the results to the corresponding response categories.
      RESULTS: For tumor assessment, the kappa statistic produced a high agreement of
      0.94 between the two methods for assessment of therapeutic response. CONCLUSION:
      The unidimensional RECIST measurement is easier to perform in order to assess
      tumor size during treatment follow-up in oncologic radiology.

PMID- 16440192
TI  - Epidemiological trends in urolithiasis: impact on our health care systems.
AB  - The progressive increase of the social cost for treating urolithiasis could be
      related to an increased incidence of the disease and/or to an increase of costs
      for diagnosing and treating renal stones. In the course of the last century, the
      incidence of renal stones has progressively increased in Europe, North America,
      and other industrialised countries. This has been explained in terms of changing
      social conditions and the consequent changes in eating habits. In contrast, renal
      stones were less frequent than in developing countries of the world but in the
      last 20 years investigators began to report high incidences of upper urinary
      stone disease also from some areas of the Third World concurring with the
      changing of economic and social conditions. Each stone episode involves the costs
      for emergency visits, diagnostic work up, and medical or surgical treatment.
      Furthermore, we have to consider the costs of follow-up visits and the costs of
      testing and drugs for stone prevention. In adjunct of direct costs for diagnosis
      and treatment, we should also take into account the indirect individual and
      social cost of workdays lost. Finally, we should estimate the costs of
      complications and outcomes of treatment with particular attention to the costs of
      chronic renal failure secondary to stone disease. The strategy of treatment of
      each stone centre involves different costs for the treatment of each single stone
      episode. On the other hand the choice of treatment can be driven by National
      Health Systems and insurance companies by their policy of reimbursement for
      different procedures. The trends of renal stone incidence will have different
      impact on health care systems in different countries. In Europe and North
      America, the peak of incidence has been probably reached but the increase of
      costs for diagnosing and treating each single stone episode will still increase
      the social cost for managing stone disease. For this reason the actual objective
      should be to optimise protocols avoiding redundant or expensive diagnostic
      procedures or inappropriate treatments. In developing countries, the incidence of
      stone disease is still increasing and it could reach peaks even higher as a
      consequence of hot climate in some geographical areas. In those countries the
      demand for treatment of symptomatic stones could dramatically increase involving
      a huge financial outlay.

PMID- 16440193
TI  - In vitro characterization of human dental pulp cells: various isolation methods
      and culturing environments.
AB  - Our purpose was to characterize human dental pulp cells isolated by various
      methods and to examine the behavior of cells grown under various conditions for
      the purpose of pulp/dentin tissue engineering and regeneration. We compared the
      growth of human pulp cells isolated by either enzyme digestion or the outgrowth
      method. Expression of dentin sialophosphoprotein, Cbfa1, and two types of
      collagen (I and III) in these cells was examined by Western blot or reverse
      transcription/polymerase chain reaction. Growth of pulp cells on dentin and in
      collagen gel was also characterized. We found that different isolation methods
      give rise to different populations or lineages of pulp cells during in vitro
      passage based on their collagen gene expression patterns. Cells isolated by
      enzymedigestion had a higher proliferation rate than those isolated by outgrowth.
      Pulp cells did not proliferate or grew minimally on chemically and mechanically
      treated dentin surface and appeared to establish an odontoblast-like morphology
      with a cytoplasmic process extending into a dentinal tubule as revealed by
      scanning electron microscopy. The contraction of the collagen matrix caused by
      pulp cells was dramatic: down to 34% on day 14. Our data indicate that (1) the
      choice of the pulp cell isolation method may affect the distribution of the
      obtained cell populations, (2) a treated dentin surface might still promote
      odontoblast differentiation, and (3) a collagen matrix may not be a suitable
      scaffold for pulp tissue regeneration because of the marked contraction caused by
      pulp cells in the matrix. The present study thus provides important information
      and a basis for further investigations pre-requisite to establishing pulp tissue
      engineering/regeneration protocols.

PMID- 16440194
TI  - Directing energy flow through quantum dots: towards nanoscale sensing.
AB  - Nanoscale sensors can be created when an expected energetic pathway is created
      and then that pathway is either initiated or disrupted by a specific binding
      event. Constructing the sensor on the nanoscale could lead to greater sensitivity
      and lower limits of detection. To this end, quantum dots (QDs) can be considered
      prime candidates for the active components. Relative to organic chromophores, QDs
      have tunable spectral properties, show less susceptibility to photobleaching,
      have similar brightness, and have been shown to display electro-optical
      properties. In this review, we discuss recent articles that incorporate QDs into
      directed energy flow systems, some with the goal of building new and more
      powerful sensors and others that could lead to more powerful sensors.

PMID- 16440195
TI  - Nano-oncology: drug delivery, imaging, and sensing.
AB  - Innovation in the last decade has endowed nanotechnology with an assortment of
      tools for delivery, imaging, and sensing in cancer research-stealthy nanoparticle
      vectors circulating in vivo, assembled with exquisite molecular control, capable
      of selective tumor targeting and potent delivery of therapeutics; intense and
      photostable quantum dot-based tumor imaging, enabling multicolor detection of
      cell receptors with a single optical excitation source; arrays of semiconducting
      nanowire and carbon nanotube sensor elements for selective multiplexed sensing of
      cancer markers without the need for probe labeling. These rapidly emerging tools
      are indicative of a burgeoning field ready to expand into medical applications.
      This review attempts to outline most of the current nanoparticle toolset for
      therapeutic release by liposomes, dendrimers, smart polymers, and virus-based
      systems. Advantages of nanoparticle-based imaging and targeting by use of
      nanoshells and quantum dots are also explored. Finally, emerging nanoelectronics
      based sensing and a global discussion on the utility of each nanoparticle system
      addresses their fundamental advantages and shortcomings in cancer research.

PMID- 16440196
TI  - Simultaneous quantification of cilostazol and its primary metabolite 3,4
      dehydrocilostazol in human plasma by rapid liquid chromatography/tandem mass
      spectrometry.
AB  - A simple, rapid, sensitive and selective liquid chromatography/electrospray
      tandem mass spectrometry method was developed and validated for the simultaneous
      quantification of cilostazol and its primary metabolite 3,4-dehydrocilostazol in
      human plasma using mosapride as an internal standard. The method involves a
      simple one-step liquid-liquid extraction with a diethyl ether and dichloromethane
      mixture (7:3). The analytes were chromatographed using an isocratic mobile phase
      on a reversed-phase C18 column and analyzed by mass spectrometry in the multiple
      reaction monitoring mode using the respective [M+H]+ ions, m/z 370/288 for
      cilostazol, m/z 368/286 for 3,4-dehydrocilostazol and m/z 422/198 for the
      internal standard. The assay exhibited a linear dynamic range of 5-2,000 ng/mL
      for cilostazol and 5-400 ng/mL for 3,4-dehydrocilostazol in human plasma. The
      lower limit of quantitation was 5 ng/mL for both cilostazol and its metabolite.
      Acceptable precision and accuracy were obtained for concentrations over the
      standard curve ranges. A run time of 2.5 min for each sample made it possible to
      analyze more than 400 human plasma samples per day. The validated method has been
      successfully used to analyze human plasma samples for application in
      pharmacokinetics, bioavailability or bioequivalence studies.

PMID- 16440197
TI  - The alphaPROX assay: fluorescence screening of the inhibitory effects of
      hydrophilic antioxidants on protein oxidation.
AB  - We report on a new and convenient high-throughput fluorescence technique for
      determining antioxidant capacities of hydrophilic food samples. The new method is
      called alphaPROX (anti protein oxidation) and is based on an equimolar complex of
      diphenylhexatriene propionic acid (DPHPA) and bovine serum albumin (BSA) in
      aqueous buffer at pH 7.4. DPHPA is a reporter fluorophore that becomes
      nonfluorescent upon free radical-induced oxidation. In a typical assay, the
      DPHPA/BSA complex is challenged with peroxyl radicals and shows almost the same
      susceptibility to oxidation as unlabeled BSA. The progress of protein oxidation
      and its inhibition by antioxidants at physiological pH is determined from the
      time-dependent decrease in DPHPA fluorescence intensity. The alphaPROX method was
      compared to other techniques frequently used to measure antioxidant capacities.
      In this article, representative results are provided for the inhibitory effects
      of pure food components, fruit juices, wines, and various polar plant extracts on
      protein oxidation.

PMID- 16440198
TI  - Expression of cyclin-dependent kinases and CDC25a phosphatase is related with
      recurrences and survival in women with peri- and post-menopausal breast cancer.
AB  - Progression through the mammalian cell cycle is regulated by cyclin-cyclin
      dependent kinase (CDKs) complexes that are activated throughout the cell cycle.
      Alteration in cell cycle control could lead to proliferation and tumourogenesis.
      This study was designed to analyse, at messenger RNA (mRNA) level, cyclins and
      CDKs involved in the retinoblastoma pathway, as well as cell division cycle 25a
      phosphatase (CDC25a), which activates some of the CDKs that were analysed. The
      aim of the study was to determine the possible prognostic relevance of these
      molecules in 73 women with peri- and post-menopausal breast cancer. Cyclins A, D1
      and E; CDKs 2, 4 and 6 and phosphatase CDC25a expression status were analysed in
      primary tumours at mRNA level, by reverse transcriptase polymerase chain reaction
      analysis in paraffin-embedded primary breast cancers. High expression levels of
      CDK2, CDK4 and CDC25a were related to tumour recurrence. Over-expression of CDK2
      and CDC25a was also associated with reduced overall survival; moreover, the CDK2
      expression level was able to define a short-living cohort of patients with tumour
      positive lymph nodes. CDK2, CDK4 and CDC25a can be used as reliable biomarkers to
      predict prognosis in women with peri- and post-menopausal breast cancer.

PMID- 16440199
TI  - Early cardiac hypertrophy induced by thyroxine is accompanied by an increase in
      VEGF-A expression but not by an increase in capillary density.
AB  - Cardiac hypertrophy in response to hyperthyroidism is well known. However, the
      effects on cardiac microcirculation are still controversial in this model. The
      present study evaluated the effects of acute administration of two different
      thyroxine (T4) dose levels on the angiogenic response in the myocardium.
      Capillary density (CD), the CD to fiber density (FD) ratio (CD/FD), and
      intercapillary distance (ICD) were assessed, as was ventricle weight (VW) to body
      weight (BW) ratio (VW/BW). Collagen I and III messenger ribonucleic acid (mRNA)
      expression and VEGF-A expression were also determined by reverse transcriptase
      polymerase chain reaction (RT-PCR). Immunohistochemical detection of
      proliferating cell nuclear antigen (PCNA) expression in endothelial cell nuclei
      was also carried out. We simulated an acute hyperthyroidism situation in male
      Wistar rats by daily intraperitoneal injection of T4 (0.025 or 0.1 mg kg(-1) day(
      1)) for 7 days. Hemodynamic parameters showed that T4 did not alter systolic
      blood pressure (SBP) but significantly increased heart rate (HR). Both T4 doses
      significantly increased VW. Morphologically, the higher T4 dose resulted in a 33%
      greater myocardial mass, which was not accompanied by alterations in collagen I
      and III mRNA expression. The CD and CD/FD parameters were significantly lower in
      the hyperthyroid rats treated with the higher dose than in the control animals,
      and PCNA-labeling analysis indicated total absence of marked capillary growth.
      However, although the acute treatment with T4 did not induce any alteration in
      capillary number and endothelial cell proliferation, the vascular endothelial
      growth factor (VEGF)-A mRNA and protein expression were significantly increased
      with the higher T4 dose. These data indicate that the cardiac hypertrophy induced
      by acute treatment with thyroid hormone precedes the angiogenic process, which
      probably occurs later.

PMID- 16440200
TI  - Molecular characterization and embryonic expression of innexins in the leech
      Hirudo medicinalis.
AB  - Gap junctions are direct intercellular channels that permit the passage of ions
      and small signaling molecules. The temporal and spatial regulation of gap
      junctional communication is, thus, one mechanism by which cell interactions, and
      hence cell properties and cell fate, may be regulated during development. The
      nervous system of the leech, Hirudo medicinalis, is a particularly advantageous
      system in which to study developmental mechanisms involving gap junctions because
      interactions between identified cells may be studied in vivo in both the embryo
      and the adult. As in most invertebrates, gap junctions in the leech are composed
      of innexin proteins, which are distantly related to the vertebrate pannexins and
      are encoded by a multi-gene family. We have cloned ten novel leech innexins and
      describe the expression of these, plus two other previously reported members of
      this gene family, in the leech embryo between embryonic days 6 and 12, a period
      during which the main features of the central nervous system are established.
      Four innexins are expressed in neurons and two in glia, while several innexins
      are expressed in the excretory, circulatory, and reproductive organs. Of
      particular interest is Hm-inx6, whose expression appears to be restricted to the
      characterized S cell and two other neurons putatively identified as presynaptic
      to this cell. Two other innexins also show highly restricted expressions in
      neurons and may be developmentally regulated.

PMID- 16440201
TI  - Allele-specific relative telomere lengths are inherited.
AB  - Previous studies have indicated that single relative telomere lengths are defined
      in the zygote. In order to explore the possibility that single telomere lengths
      segregate in families, we compared relative telomere lengths obtained from
      allelic chromosome extremities transmitted from parent to child, representing a
      total of 31 independent meiotic events. We find a significant positive
      correlation of 0.65 (P=0.0004) between these telomere lengths, whereas the
      correlation between the non-transmitted parental homologue and the transmitted
      homologue in the child is not statistically significant (r=0.16; P=0.195). This
      study indicates that, even though there is a telomerase-mediated
      maintenance/elongation of telomeres in germ cells, allele-specific relative
      telomere lengths are preserved in the next generation.

PMID- 16440204
TI  - [Active studies of the Working Association for Urological Oncology (AUO) in
      2006].

PMID- 16440202
TI  - Spinal lumbar synovial cysts. Diagnosis and management challenge.
AB  - Sophisticated and newer imaging capabilities have resulted in increased reporting
      and treatment options of spinal lumbar synovial cysts (LSS). Most of the patients
      with lumbar cysts tend to be in their sixth decade of life with a slight female
      predominance. The incidence of LSS is thought to be less than 0.5% of the general
      symptomatic population. They may be asymptomatic and found incidentally or the
      epidural growth of cysts into the spinal canal can cause compression of neural
      structures and hence associated clinical symptoms. Most of the symptomatic LSS
      patients present with radicular pain and neurological deficits. Spinal synovial
      cysts are commonly found at L4-5 level, the site of maximum mobility. They may be
      unilateral or bilateral and at one or multilevel. MRI is considered the tool of
      choice for its diagnosis. The etiology of LSS is still unclear, but underlying
      spinal instability, facet joint arthropathy and degenerative spondylolisthesis
      has a strong association for worsening symptoms and formation of spinal cysts.
      Synovial cysts resistant to conservative therapy should be treated surgically.
      Resection and decompression with or without fusion and instrumentation remains an
      appropriate option. Synovial cysts may recur following surgery. The optimal
      approach for patients with juxtafacet LSS remains unclear. The best surgical
      treatment option for each particular individual should be tailored depending upon
      the symptoms, radiological findings and other co morbidities.

PMID- 16440203
TI  - [The task of the HNO specialist by Hearing Aid fitting. Part 1: indications,
      special diagnostic tests, prescription].
AB  - The first part of the article deals with the indication of fitting, which mainly
      is given when the communication is impaired, not only in dialogue with one
      person, but also in conversation with several persons and in noisy surrounding.
      Yet, the healthy insurances cover only the expenses if the guidelines on relief
      aid are considered, which are exactly listed in this article. Bevor starting the
      fitting of an Hearing Aid, special diagnostic tests are necessary, such as pure
      tone audiogram, speech audiogram including dB(opt), freefield measurement in
      noise, and several retrocochlear tests, as well as tinnitus determination and
      masking with narrow-band and broad-band noise. Most important is the correct
      filling in the form "Ohrenarztliche Verordnung einer Horhilfe", including the
      necessity of renewal. In addition, it is necessary to accentuate the need of
      trying out several Hearing Aids and to let the patient know that digital Hearing
      Aids will not be covered by the health insurance.

PMID- 16440205
TI  - [Value of surfactant replacement therapy in the treatment of acute respiratory
      distress syndrome].
AB  - Acute respiratory distress syndrome (ARDS) is a common, devastating clinical
      problem arising from a number of conditions, such as pneumonia, trauma or sepsis.
      Because of its significant mortality and morbidity, ARDS has been in the focus of
      extensive experimental and clinical research. Since there is little doubt that
      alterations of the surfactant system contribute to lung dysfunction and the onset
      of ARDS, several clinical studies examined the therapeutic safety and efficacy of
      a surfactant replacement therapy. Clinical experience with exogenous surfactant
      has proven inconsistent as a therapeutic modality for adult patients with ARDS.
      This is mainly due to a number of confounding factors, e.g. severity of injury at
      the time of treatment, dosing regimes and delivery methods used in different
      trials. However, current data suggest that patients with direct ARDS (e.g.
      pneumonia, aspiration) could benefit from surfactant replacement therapy rather
      than patients with indirect ARDS (e.g. sepsis, trauma). Although surfactant
      replacement therapy has been shown to significantly reduce mortality in neonates
      with ARDS, there has been no large randomised clinical trial showing that
      exogenous surfactant improves outcome in adults with respiratory failure.
      Therefore, surfactant therapy cannot be recommended for routine clinical use in
      adult patients and has to be considered as a last resort treatment.

PMID- 16440207
TI  - Comparison of reduced and standard light application in photodynamic therapy of
      the eye in two rabbit models.
AB  - BACKGROUND: Current PDT treatment for age-related macular degeneration uses a
      standard radiant exposure of 50 J/cm(2) at an irradiance of 600 mW/cm(2).
      However; there is a general problem with the unusually high irradiance; in fact,
      the rate of photochemical production of singlet oxygen may be limited by
      insufficiently oxygenized neovascular tissue. It was the aim of this study to
      evaluate the efficacy of verteporfin (Visudyne) photoactivation to induce
      thrombosis of choriocapillaries and in experimentally induced corneal
      neovascularizations in rabbits by varying irradiance and retinal radiant
      exposure. MATERIALS AND METHODS: The light-dose threshold to induce micro
      thrombosis in the choriocapillaries (seven eyes) and in corneal
      neovascularizations (eight eyes) of Chinchilla-Bastard rabbits using different
      retinal irradiances (100 and 600 mW/cm(2)) at different radiant exposures (20,
      10, 5, 2.5, 1.25, 0.62, and 0.3 J/cm(2)) was evaluated. Induction of
      neovascularizations was performed 7 days prior to PDT treatment using
      intracorneal silk sutures. A dose of 2 mg/kg verteporfin was intravenously
      infused 10 min before standard PDT. The criterion for vascular thrombosis was
      vessel closure as determined by fluorescein angiography 1 h and 1 day post
      exposure. RESULTS: Experiments on the choroid revealed vessel closure 1 h after
      irradiation at ED(50) = 10.8 J/cm(2) (both 600 and 100 mW/cm(2)) and after 24 h
      at ED(50) = 2.4 J/cm(2) (600 mW/cm(2)) versus 1.8 J/cm(2) (100 mW/cm(2)). Vessel
      closure was enhanced at irradiation with 100 mW/cm(2). Regarding corneal
      neovascularizations, vessel thrombosis was observable by dark appearance of
      irradiated clotted neovascular tissue and angiographically by a lack of leakage
      at ED(50) thresholds of 0.62 J/cm(2) (1 h) and 0.41 J/cm(2) (1 day) for 100
      mW/cm(2) and of 0.99 J/cm(2) (1 h), and 0.67 J/cm(2) (1 day) for 600 mW/cm(2).
      Thus in both experiments thresholds for vessel closure were reduced by a factor
      of 1.5 for the lower intensity. Histology revealed more selective vessel
      occlusion without RPE and photoreceptor damage for 100 mW/cm(2) rather than 600
      mW/cm(2) intensity at threshold irradiation. CONCLUSION: Low-intensity PDT with
      verteporfin for neovascular tissue seems to be more effective than regular high
      intensity PDT. Future preclinical trials should address the issue of proper
      dosimetry for effective PDT in age-related macular degeneration.

PMID- 16440206
TI  - Optineurin gene is not involved in the common high-tension form of primary open
      angle glaucoma.
AB  - PURPOSE: To assess the influence of optineurin in the more common high-tension,
      primary open-angle glaucoma (POAG). METHODS: Eighteen sporadic cases and 35
      probands from 35 familial cases, including three families with one member having
      normal-tension glaucoma (NTG), were enrolled. Using transgenomic WAVE denaturing
      high-performance liquid chromatography (DHPLC), all coding portion of the
      optineurin gene (from exon 4 to exon 16) was analyzed. Samples displaying an
      altered elution profile were sequenced to confirm and identify sequence variants.
      Exon 4 containing the previously reported p.E50K (Glu50Lys) recurrent mutation
      (covering 13% of normotensive cases) was entirely sequenced. RESULTS: We did not
      detect the mutation p.E50K, and we did not find any other pathogenic mutation. A
      putative splice-site mutation was detected in one family. Extension of
      segregation analysis to additional family members and mRNA investigation failed
      to establish a certain involvement of this mutation with the disease. We detected
      a number of common polymorphisms, including the previously reported p.M98K
      (Met98Lys) variant. CONCLUSIONS: In this population, mutations in the optineurin
      gene are not associated with adult-onset primary POAG.

PMID- 16440208
TI  - Vitreoretinal surgery of the posterior segment for explosive trauma in terrorist
      warfare.
AB  - BACKGROUND: To describe surgical management and establish anatomic and visual
      results of patients with explosive ocular trauma in terrorist attacks treated
      with extreme vitreoretinal surgery. METHODS: Retrospective study of clinical
      records (6-month follow-up) of patients with visual acuity (VA) of light
      perception or better with posterior segment injuries [vitreous hemorrhage,
      retinal detachment (RD), intra-ocular foreign bodies (IOFB), perforating trauma
      (PT)] from explosive weapons who underwent vitreoretinal surgery. We reviewed the
      demographic characteristics, type of weapon, time between injury and surgery, VA
      at arrival and 6 months after surgery, and type of trauma according to the
      International Trauma Classification. RESULTS: Fifty-seven out of 236 patients
      with ocular injuries from explosive weapons were included in the study; all of
      them were military men, average age 22 years (range 16-53 years). The average
      time between the blast and primary closing was 1 day, and 10 days between primary
      closing and vitreoretinal surgery. Open traumas by laceration accounted for 96%
      of cases and 4% were closed traumas; 76% of the eyes had IOFB, of which 18%
      involved PT; 5% had endophthalmitis. Contusion was the diagnosis for 100% of the
      closed traumas. Of the open traumas, 40% were localized at zone I, 44% at zone
      II, and 16% at zone III. Upon arrival, 98% of patients had VA 20/800-LP and 2%
      had >20/40. The patients with closed trauma had the injuries at zone III and
      presented VA 20/800-LP. All patients underwent posterior vitrectomy, scleral
      buckling, endotaponade and when required, lensectomy (82%), IOFB removal (72%),
      and/or retinectomy (25%). Postoperative VA improved in 43% of the patients,
      stabilized in 41% and evolved to NLP in 15% of the cases. Initial expressions of
      ocular trauma such as RD, PT and endophthalmitis suggest bad prognosis.
      CONCLUSIONS: We presented a series of patients with severe ocular trauma of the
      posterior segment from explosive weapons. These patients were treated according
      to our surgical protocol with extreme vitreoretinal surgery within the first 2
      weeks after the blast; with our procedure we obtained stabilization or
      improvement of the VA for 84% of the cases.

PMID- 16440209
TI  - The effect of conjugated equine oestrogen on diabetes incidence: the Women's
      Health Initiative randomised trial.
AB  - AIMS/HYPOTHESIS: Recent clinical trials have found that the combination of
      conjugated equine oestrogen (CEO) and medroxyprogesterone has a protective effect
      on the incidence of type 2 diabetes. To determine the effect of CEO alone on the
      incidence of diabetes mellitus in postmenopausal women, we analysed the results
      of the Women's Health Initiative oestrogen-alone trial. METHODS: The Women's
      Health Initiative is a randomised, double-masked trial comparing the effect of
      daily 0.625 mg CEO with placebo during 7.1 years of follow-up of 10,739
      postmenopausal women who were aged 50-79 years and had previously had a
      hysterectomy. Diabetes incidence was ascertained by self-report of treatment with
      insulin or oral hypoglycaemic medication. Fasting glucose, insulin and
      lipoproteins were measured in an 8.6% random sample of study participants, at
      baseline and at 1, 3 and 6 years. RESULTS: The cumulative incidence of treated
      diabetes was 8.3% in the oestrogen-alone group and 9.3% in the placebo group
      (hazard ratio 0.88, 95% CI 0.77-1.01, p=0.072). During the first year of follow
      up, a significant fall in insulin resistance (homeostasis model assessment of
      insulin resistance) in actively treated women compared with the control subjects
      (Year 1 baseline between-group difference -0.53) was seen. However, there was no
      difference in insulin resistance at the 3- or 6-year follow-up.
      CONCLUSIONS/INTERPRETATION: Postmenopausal therapy with oestrogen alone may
      reduce the incidence of treated diabetes. The effect is smaller than that seen
      with oestrogen plus progestin. CEO should not, however, be used with the
      intention of preventing diabetes, as its well-described adverse effects preclude
      long-term use for primary prevention.

PMID- 16440210
TI  - Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and
      beta cell lines.
AB  - AIMS/HYPOTHESIS: Activin receptor-like kinase 7 (ALK7), a member of the type I
      receptor serine/threonine kinases of the TGF-beta superfamily, was recently
      reported to regulate cell proliferation and apoptosis. We hypothesised that ALK7
      may play a role in modulating pancreatic beta cell proliferation and/or
      apoptosis. METHODS: We detected ALK7 expression in beta cells using RT-PCR,
      immunostaining and western blotting. Constitutively active, dominant negative or
      wild-type ALK7 was introduced into beta cells using adenoviral delivery.
      Proliferation was assessed using (3)H-thymidine incorporation and apoptosis was
      quantified using terminal deoxynucleotidyl transferase biotin-dUTP nick end
      labelling detection, DNA degradation analysis and caspase-3 assays. RESULTS:
      Induction of constitutively active ALK7 in beta cells resulted in growth
      inhibition and enhanced apoptosis; no effect was seen with INS-1 cells expressing
      wild-type or dominant negative ALK7. Elevated glucose concentrations and fatty
      acid (palmitate) markedly increased expression levels of ALK7 transcripts and
      proteins in INS-1 and rat islets and increased beta cell apoptosis. Activation of
      ALK7 increased Smad2 phosphorylation, reduced protein kinase B (Akt) kinase
      activity and was associated with increased levels of the bioactive forms of
      caspase-3, whereas co-expression of constitutively active ALK7 with dominant
      negative Smad2 or constitutively active Akt significantly diminished ALK7-induced
      growth inhibition and apoptosis in INS-1 cells. Although overexpression of
      constitutively active Akt significantly reduced ALK7-induced growth inhibition
      and ALK7-enhanced beta cell apoptosis, ALK7-stimulated Smad2 phosphorylation was
      not affected. CONCLUSIONS/INTERPRETATION: These results suggest that the
      pancreatic beta cell apoptosis induced by ALK7 activation occurs via the
      activation of two distinct downstream pathways: the suppression of Akt activation
      and the activation of the Smad2-caspase-3 cascade.

PMID- 16440212
TI  - Vacuolar citrate/H+ symporter of citrus juice cells.
AB  - We have isolated a cDNA, designated Citrus sinensis citrate transporter 1 CsCit1
      encoding a novel vacuolar citrate/symporter. Immunoblots using antibodies raised
      against CsCit1 showed that the protein is localized to the juice sac cell
      vacuoles. The highest expression of CsCit1 and the amount of protein in the juice
      sac cell vacuoles coincided with the developmental stage at which the vacuolar
      citrate content began declining with the concomitant increase in vacuolar pH.
      Vacuoles from Sacharomyces cereviseae expressing CsCit1 displayed a citrate
      dependent H(+) efflux, and our results clearly demonstrate that CsCit1 is able to
      mediate the electroneutral co-transport of H(+) and citrate ions, since the
      citrate-dependent H(+) fluxes are not affected by changing the electrical
      potential difference across the tonoplast. The roles of CsCit1 in mediating
      citrate efflux from the vacuole and on citric acid homoestasis in Citrus juice
      sac cells are discussed.

PMID- 16440211
TI  - Downregulation of protein kinase B/Akt-1 mediates INS-1 insulinoma cell apoptosis
      induced by dominant-negative suppression of hepatocyte nuclear factor-1alpha
      function.
AB  - AIMS/HYPOTHESIS: Inactivating mutations in Tcf1, which encodes the transcription
      factor hepatocyte nuclear factor (HNF)-1alpha, cause maturity-onset diabetes of
      the young-3. We have previously shown that a dominant-negative mutant (DN-HNF
      1alpha) renders INS-1 insulinoma cells sensitive to the mitochondrial apoptosis
      pathway, but the underlying alterations in signal transduction remain unknown.
      MATERIALS AND METHODS: Using a reverse tetracycline-dependent transactivator
      system, DN-HNF-1alpha-induced apoptosis was assessed by immunoblotting and
      caspase assays. Alterations in AKT1 kinase/protein kinase B (AKT1) survival
      signalling during DN-HNF-1alpha-induced apoptosis were investigated by phospho
      specific immunodetection and transient transfection experiments. RESULTS:
      Induction of DN-HNF-1alpha caused significant changes in the activation-specific
      phosphorylation status of AKT1 that were preceded by a downregulation of Ins1
      gene transcription. Phosphorylation of AKT1 at Ser473 was dramatically reduced
      after 36 to 48 h of DN-HNF-1alpha induction and coincided with maximal apoptosis
      activation. Overexpression of a constitutively active mutant of Akt1 rescued INS
      1 cells from DN-HNF-1alpha-induced apoptosis, while ectopic expression of a
      dominant-negative mutant mimicked the effect of DN-HNF-1alpha on apoptosis
      activation. Pharmacological suppression of growth factor survival signalling
      through administration of the phosphatidylinositol-3 kinase (PI-3K) inhibitor
      wortmannin accelerated the induction of apoptosis by DN-HNF-1alpha.
      CONCLUSIONS/INTERPRETATION: These data suggest that a decrease in PI-3K/AKT1
      survival signalling mediates DN-HNF-1alpha-induced apoptosis in insulin-secreting
      cells.

PMID- 16440213
TI  - Low-temperature tolerance and genetic potential in wheat (Triticum aestivum L.):
      response to photoperiod, vernalization, and plant development.
AB  - It is frequently observed that winter habit types are more low-temperature (LT)
      tolerant than spring habit types. This raises the question of whether this is due
      to pleiotropic effects of the vernalization loci or to the linkage of LT
      tolerance genes to these vernalization loci. Reciprocal near-isogenic lines
      (NILs) for alleles at the Vrn-A1 locus, Vrn-A1 and vrn-A1, determining spring and
      winter habit respectively, in two diverse genetic backgrounds of wheat (Triticum
      aestivum L.) were used to separate the effects of vernalization, photoperiod, and
      development on identical, or near identical, genetic backgrounds. The vrn-A1
      allele in the winter lines allowed full expression of genotype dependent LT
      tolerance potential. The winter allele (vrn-A1) in a very cold tolerant genetic
      background resulted in 11 degrees C, or a 2.4-fold, greater LT tolerance compared
      to the spring allele. Similarly, the delay in development caused by short-day
      (SD) versus long-day (LD) photoperiod in the identical spring habit NIL resulted
      in an 8.5 degrees C or 2.1-fold, increase in LT tolerance. The duration of time
      in early developmental stages was shown to underlie full expression of genetic LT
      tolerance potential. Therefore, pleiotropic effects of the vernalization loci can
      explain the association of LT tolerance and winter habit irrespective of either
      the proposed closely linked Fr-A1 or the more distant Fr-A2 LT-tolerance QTLs.
      Plant development progressively reduced LT-acclimation ability, particularly
      after the main shoot meristem had advanced to the double ridge reproductive
      growth stage. The Vrn-1 genes, or other members of the flowering induction
      pathway, are discussed as possible candidates for involvement in LT-tolerance
      repression.

PMID- 16440215
TI  - [Stroke treatment in the 2006 German diagnosis-related group system].
AB  - The 2006 version of the German diagnosis-related group (DRG) system distinguishes
      for the first time between different forms of treatment for acute stroke. This
      was made possible through cooperation of the German Stroke Society (Deutsche
      Schlaganfall Gesellschaft) in further development of the German procedure
      classification (OPS) and G-DRG system. The 2005 procedure codes for complex
      neurologic treatment of acute stroke (OPS 8-981) collated treatment methods for
      the first time in a data base. Their consideration in the 2006 German DRG system
      was made possible by further data collection from participating hospitals. Hence
      the complex neurologic treatment of acute stroke now serves as a qualifying
      criterion for seven higher weighted DRGs. Even though this might not lead
      directly to a rise in a given hospital's total revenue, it can ease adjustments
      to the DRG price system and present a more realistic picture of the relationships
      between the various departments within a hospital.

PMID- 16440214
TI  - The importance of cysteine cathepsin proteases for placental development.
AB  - The typically lysosomal family of cysteine cathepsin proteases has been
      implicated in the development of the placenta in particular, from studies in the
      mouse. Here, we analysed overall expression, regulation and presence of
      transcript isoforms of cysteine cathepsins during human extra-embryonic
      development. All 11 family members are expressed in human placental tissues, and
      many are differentially regulated during gestation. Several cysteine cathepsins
      exhibit deregulated expression levels in placentas from pregnancies complicated
      by pre-eclampsia. The localization of cathepsin B predominantly in placental and
      decidual macrophages suggests a role in the physiological functions of these
      cells in mediating villous angiogenesis and decidual apoptosis. Cathepsin L
      levels are highest in a subpopulation of invasive cytotrophoblasts. Reflecting
      the expression pattern of two murine cathepsins, these data give insights into
      the evolutionary conservation of cathepsin function that is not necessarily
      exhibited by gene pairs defined by highest sequence similarity. Furthermore,
      cathepsin L protein localization in uterine epithelial cells demonstrates the in
      vivo occurrence of intranuclear cathepsin L isoforms. The zonally restricted
      expression of cathepsin in the syncytiotrophoblast may be important for the
      metabolic breakdown of maternal nutrients. Overall, the distribution and abnormal
      expression levels in pre-eclamptic placentas indicate that cysteine cathepsins
      may play important roles during normal placentation and in the etiology of pre
      eclampsia.

PMID- 16440217
TI  - Role of magnetic resonance imaging for evaluation of tumors in the cardiac
      region.
AB  - The aim of this study was to review the role of MRI in the assessment of heart
      neoplasm, 25 cases with heart neoplasm (10 myxoma, 6 rhabdomyoma, 5 angiosarcoma,
      2 mesothelioma, 1 lymphoma, and 1 fibroma) were examined with MRI and
      echocardiography. Multislice T1- and T2-weighted spin-echo images and static
      gradient-echo images were taken in appropriate directions with electrocardiogram
      gating. Gadolinium enhancement was performed in 21 cases. Transthoracic
      echocardiography was performed in all cases. Except for the 5 patients with
      rhabdomyoma, the pathological diagnosis was obtained. MRI proved to be useful for
      tissue characterization of myxoma, angiosarcoma, mesothelioma, and fibroma in
      cases with tuberous sclerosis. MRI also proved to be useful for detection of the
      tumor, depiction of contour, relation with other cardiac structures, in cases
      with myxoma, angiosarcoma, mesothelioma, lymphoma, and fibroma. In the
      differential diagnosis, MRI provided important information in cases with myxoma,
      rhabdomyoma, angiosarcoma, and fibroma. In cases with tumors expanding into the
      mediastinum, such as mesothelioma and fibroma in this report, MRI was useful in
      determining the location and border. In cases with tumors adjacent to
      pericardium, MRI was useful in detecting pericardial invasion. Gadolinium
      enhancement added useful information in cases with myxoma, rhabdomyoma,
      angiosarcoma, and mesothelioma. The role of MRI with and without Gd enhancement
      differs somewhat in individual types of heart neoplasm, and adaptation must be
      considered in each kind of neoplasm. On the other hand, MRI is an essential
      examination in all cases with a cardiac mass, which has not been diagnosed, since
      it may provide useful information for the differential diagnosis.

PMID- 16440216
TI  - Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols.
AB  - ABCG5 and ABCG8 are two ATP-binding cassette half-transporters that belong to the
      G family members. They were identified as proteins that are mutated in a rare
      human disorder, sitosterolemia, and their identification led to the completion of
      the physiological pathways by which dietary cholesterol, as well as
      noncholesterol sterols, traffics in the mammalian body. These proteins are likely
      to function as heterodimers, and current evidence suggests that these proteins
      are responsible for the majority of sterol secretions into bile, thus may define
      the long sought-after biliary sterol transporters. This review will focus on some
      of the backgrounds of this physiology, the genetics and regulation of these
      genes, as well as our current understanding of their functions. This review will
      also highlight the current limitations in our knowledge gap.

PMID- 16440219
TI  - MRI and CT revealing carcinoid heart disease.
AB  - Carcinoid heart disease is a frequent complication of the carcinoid syndrome,
      usually presenting as right-sided valvular heart disease. Although the diagnosis
      is most often made with cardiac ultrasound, MRI and CT are valuable techniques
      for diagnosing carcinoid heart disease.

PMID- 16440218
TI  - Primary localized amyloidosis of the urinary bladder.
AB  - We report a rare case of localized form of primary amyloidosis (amyloidoma) of
      the urinary bladder with CT and MR findings. Clinically, it is difficult to
      distinguish from invasive transitional cell carcinoma and inflammatory lesion. We
      think that the MR intensity on T2-weighted images is helpful in making the
      diagnosis.

PMID- 16440220
TI  - Accessory ossicles and sesamoid bones of the ankle and foot: imaging findings,
      clinical significance and differential diagnosis.
AB  - Accessory ossicles and sesamoid bones are frequent findings in routine
      radiographs of the ankle and foot. They are commonly considered fortuitous and
      unrelated to the patient's complaint; however, they may eventually cause painful
      syndromes or degenerative changes in response to overuse and trauma. They may
      also suffer or simulate fractures. Our aim was to review, illustrate and discuss
      the imaging findings of some of the more frequent accessory ossicles and sesamoid
      bones of the ankle and foot region, with particular emphasis on those that may be
      of clinical significance or simulate fractures.

PMID- 16440221
TI  - Giant cavernoma of the brain stem: value of delayed MR imaging after contrast
      injection.
AB  - Cavernous angiomas are vascular malformations composed of slowly perfused,
      sinusoidal vessels which can be located in any part of the central nervous
      system. Whereas diagnosis is mostly straightforward in typical cases, some
      lesions may present in unusual locations or with unusual imaging characteristics.
      Because of the slow perfusion, contrast enhancement is not regarded as a
      characteristic imaging feature of cavernomas. We report a large brain stem
      cavernoma with signs of recent bleeding, in which the differential diagnosis
      against other mass lesions was facilitated by the demonstration of slow, but
      intense, contrast enhancement on MRI 1 h after contrast injection. We conclude
      that contrast enhancement in delayed images may contribute to a safe diagnosis of
      cavernous haemangiomas and should be performed in atypical cases.

PMID- 16440222
TI  - Diffusion MRI findings in phenylketonuria.
AB  - Two patients with phenylketonuria were studied who were under dietary control
      since infancy, and who were mentally normal. Diffusion MRI was obtained using a
      spin-echo, echo-planar sequence with a gradient strength of 30 mT/m at 1.5 T. A
      trace sequence (TR=5700 ms, and TE=139 ms) was used, acquired in 22 s. Heavily
      diffusion-weighted (b=1000 mm(2)/s) images, and the apparent diffusion
      coefficient (ADC) values from automatically generated ADC maps were studied.
      There were two different patterns in these two patients, restricted and increased
      diffusion patterns. Restricted diffusion pattern consisted of high-signal on
      b=1000 s/mm(2) images with low ADC values ranging from 0.46 to 0.57 x 10(-3
      )mm2/s. Increased diffusion pattern consisted of normal b=1000 s/mm(2 )images
      with high ADC values ranging from 1.37 to 1.63 x 10(-3 )mm2/s. It is likely that
      these values reflected presence of two different histopathological changes in
      phenylketonuria or reflected different stages of the same disease.

PMID- 16440223
TI  - Diffuse spinal and intercostal nerve involvement in chronic inflammatory
      demyelinating polyradiculoneuropathy: MRI findings.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon
      demyelinating disorder with a relapsing and remitting or continuously progressive
      course. Hypertrophic nerve roots, sometimes associated with gadolinium
      enhancement, has been reported more commonly in lumbar spine and less commonly in
      the brachial plexus and cervical roots; however, diffuse involvement of
      intercostal nerves bilaterally has never been reported previously. We present MRI
      findings which include diffuse enlargement and mild enhancement of roots and
      extraforaminal segments of nerves in all segments except a short segment between
      T12-L2 as well as all the intercostal nerves in a case of CIPD with a 10-year
      history.

PMID- 16440224
TI  - Spontaneous intrahepatic portosystemic venous shunt in leptospirosis: is it a
      rare association or coincidence?

PMID- 16440225
TI  - Extremely tortuous superior cerebellar artery.

PMID- 16440226
TI  - Safety of the long-time monthly triple dose of a Gd-based contrast agent.

PMID- 16440227
TI  - MR findings of renal malignant fibrous histiocytoma.

PMID- 16440228
TI  - Cholangiographic magnetic resonance findings in post-radiation therapy
      extrahepatic biliary stricture.

PMID- 16440229
TI  - CT features of uterine torsion.

PMID- 16440230
TI  - Cystic angiomatosis with splenic involvement: unusual MRI findings.
AB  - Cystic angiomatosis is a rare disorder with a poor prognosis. We describe a case
      of a 33-year-old woman who presented with longstanding bone pain, hemolytic
      anemia, and an enlarged spleen. Radiologically, multiple osseous lesions with a
      mixed pattern of lytic and sclerotic areas were seen within the shoulders, spine,
      and pelvis. On CT and MRI of the abdomen, the spleen was markedly enlarged, with
      internal hyperdense foci on non-contrast CT scan, corresponding to low signal
      intensity areas on all MR pulse sequences. After administration of contrast, a
      mottled enhancement pattern throughout the entire spleen was seen both on CT and
      MRI. Cystic angiomatosis was proven by histological analysis of a biopsy specimen
      of an involved vertebra and histopathological examination of the spleen after
      subsequent splenectomy. This is the first report of a patient with disseminated
      cystic angiomatosis with splenic involvement in which the MRI features differ
      from the previous reports. Instead of the usual pattern consisting of multiple
      well-defined cystic lesions, a diffuse involvement replacing the entire spleen,
      with heterogeneous signal intensities on T2-weighted images and heterogeneous
      enhancement pattern, was seen in our patient.

PMID- 16440231
TI  - Diseases of the cecum: a CT pictorial review.
AB  - Cecal pathology is commonly encountered and may represent a diagnostic challenge
      in patients with either acute or chronic clinical presentations. Although
      appendicitis accounts for the majority of surgical conditions presenting with
      right lower quadrant pain, readers should be aware of the broad spectrum of cecal
      pathologies and characteristic CT findings, which can be useful in establishing
      the correct diagnosis.

PMID- 16440232
TI  - Rectal inflammation as first manifestation of graft-vs-host disease: radiologic
      pathologic findings.
AB  - Graft-vs-host disease (GVHD) is a common, life-threatening complication of bone
      marrow transplantation that frequently involves the gastrointestinal tract. Since
      symptoms are typically nonspecific, radiologic examination is often performed to
      reach a diagnosis. To the best of our knowledge, this is the first reported
      radiologic description of a case of rectal involvement as the first manifestation
      of GVHD. The differential diagnosis of segmental rectal wall thickening in a
      patient following bone marrow transplantation should include GVHD.

PMID- 16440233
TI  - MR findings of prostatic urethral polyp in an adult.
AB  - We report MR imaging characteristics of a prostatic urethral polyp in a 35-year
      old man. Traditionally, the methods of diagnosis include computed tomography,
      transrectal sonography, voiding cysto-urethrography, intravenous pyelography,
      urethroscopy, and cystoscopy. To our knowledge, MR findings have not been
      previously described. In this case, MR imaging clearly demonstrated a polypoid
      tumor located in the prostatic urethra with a stalk connected to the bladder
      neck. A pathological study revealed the polyp consisted of a fibrovascular core
      covered with a double layered, prostatic-type epithelium.

PMID- 16440234
TI  - A case of missing mitral valve leaflet: radiological detection.
AB  - Intravascular foreign bodies may be introduced into the circulation as a
      complication of minimally invasive or interventional techniques, or during
      cardiac valve surgery. Prosthetic heart valve leaflets have been rarely described
      as intravascular foreign bodies. Herein we report a case of prosthetic heart
      valve leaflet embolization to the aortic bifurcation with computed tomography and
      ultrasonography findings, and the importance of radiographic imaging in the
      localization of missing leaflet fragment is pointed out.

PMID- 16440235
TI  - Bilateral congenital absence of the internal carotid artery.
AB  - Bilateral congenital absence of the internal carotid artery was incidentally
      found in an 11-year-old boy. Magnetic resonance imaging showed a normal-appearing
      brain that was entirely supplied by the vertebrobasilar system, and CT confirmed
      the absence of the bony carotid canals. Although most reported patients with
      agenesis of both internal carotid arteries presented with cerebrovascular
      lesions, this case demonstrates that this rare malformation may be asymptomatic.

PMID- 16440236
TI  - MRI findings of hypoxic cortical laminar necrosis in a child with hemolytic
      anemia crisis.
AB  - We present magnetic resonance imaging findings of a 5-year-old girl who had a
      rapidly installing hemolytic anemia crisis induced by trimethoprim
      sulfomethoxazole, resulting in cerebral anoxia leading to permanent damage.
      Magnetic Resonance imaging revealed cortical laminar necrosis in arterial border
      zones in both cerebral hemispheres, ischemic changes in subcortical white matter
      of left cerebral hemisphere, and in the left putamen. Although cortical laminar
      necrosis is a classic entity in adulthood related to conditions of energy
      depletions, there are few reports available in children. A wide review of the
      literature is also presented.

PMID- 16440237
TI  - Sacral pseudotumor complicating iliac bone harvest: radiographic, CT and MRI
      appearances.
AB  - We present the imaging appearances of a lytic pseudotumor in the right sacral ala
      presenting with referred pain to the right thigh. Subsequent imaging revealed the
      presence of a cystic lesion arising at the site of previous bone graft harvest;
      CT-guided aspiration yielded synovial fluid presumed to arise from the contiguous
      sacroiliac joint.

PMID- 16440238
TI  - Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic
      arteritis.
AB  - A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation
      in a 10-year-old girl with consecutive immunocompromising therapy. Neither
      digital subtraction angiography (DSA) nor computed tomographic angiography showed
      signs of intracranial vascular malformations. One month before the lethal SAH
      occurred, she had developed arterial hypertension and attacks of severe headache
      with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of
      the left thalamus. Pathologic findings established the rare diagnosis of SAH due
      to aspergillosis-related mycotic arteritis. Imaging characteristics are
      presented.

PMID- 16440239
TI  - [Extreme photosensitivity since childhood].

PMID- 16440240
TI  - Preparing speech-language pathologists as family-centered practitioners in
      assessment and program planning for children with autism spectrum disorder.
AB  - Family-centered care is a practice model that has been described in the
      literature for the past two decades. The evidence shows that when family-centered
      care is practiced, outcomes are enhanced for children with autism and other
      disabilities and their families and teams. This article reviews two innovative
      programs that practiced family-centered care in assessment and program planning
      for children with autism spectrum disorders (ASD). The research indicates that
      the essential training elements required to transform speech-language
      pathologists (SLPs) from understanding family-centered care to being family
      centered practitioners includes a focus on technical and leadership skills as
      well as a variety of experiences with families who have children with ASD.
      Preservice programs preparing SLPs and other health professionals must
      incorporate these essential elements of family-centered care training into their
      curricula. SLPs who are already practicing can use these key elements as a guide
      in seeking professional development opportunities.

PMID- 16440241
TI  - Developing and implementing early intervention plans for children with autism
      spectrum disorders.
AB  - Autism spectrum disorder (ASD) is a complex neurobiological disability that
      affects communication, social interaction, and behavior and can now be reliably
      diagnosed in children as young as 2 years of age. Research indicates that
      intensive early intervention is critical for improving outcomes for children with
      ASD and their families. There is, however, scant research describing effective
      intervention programs for children under the age of 3. Because communication is
      one of the core developmental areas affected by ASD and is likely to be an area
      parents consistently identify as a priority, speech-language pathologists are in
      a critical position to support children with ASD and their families at the
      earliest stage of intervention. The purpose of this article is to present
      promising practices for speech-language pathologists to use while collaboratively
      developing and implementing early intervention plans for children with ASD and
      their families.

PMID- 16440242
TI  - Language play in children with autism spectrum disorders: implications for
      practice.
AB  - The purpose of this article is to present evidence for the use of language play
      by children with autism spectrum disorders (ASD) within the context of play with
      peers. A conceptual framework for the development of language play is described.
      This framework, which is supported by the literature on language play in
      typically developing children, is used to assess patterns of language play in
      children with ASD. The findings of a descriptive study are used to provide
      evidence for language play in the speech of children with ASD during interactions
      with typical peers and show that children with ASD use language play in a similar
      way as their typically developing peers with the exception of age of occurrence.
      Implications for clinicians in their work with children with ASD are discussed as
      they relate to the existence of language play in children with ASD and the
      function of language play as a tool for language learning.

PMID- 16440243
TI  - Peer play interventions to support the social competence of children with autism
      spectrum disorders.
AB  - Children with autism spectrum disorders (ASD) have difficulty connecting with
      others because they often lack the communication, social interaction, and play
      skills necessary for developing relationships with their peers. This article
      highlights the characteristics of four peer intervention programs described in
      the literature that have been successful in facilitating the social connections
      between children with ASD and their typical peers. The environments established
      for intervention, the role of the typical peer, and the role of the adult are
      described across the four programs. A fifth peer intervention program is
      introduced that focuses on establishing peer connections in the home of the child
      with ASD while facilitating bids and responses for behavior regulation, social
      interaction, and joint attention in the child with ASD and his or her typical
      peer in the context of play. Implications for practice are provided as clinicians
      consider the role peer mediation has in intervention planning and implementation
      for children with ASD.

PMID- 16440244
TI  - Using social stories and comic strip conversations to promote socially valid
      outcomes for children with autism.
AB  - Very little is documented regarding the efficacy of social stories and comic
      strip conversations for promoting an understanding of social situations and the
      appropriate social behaviors of individuals with autism spectrum disorder (ASD).
      In addition, few studies on the efficacy of social stories have examined whether
      outcomes are socially valid. The purpose of this article is to respond to some of
      the gaps in the literature on the efficacy of a frequently used intervention for
      children with ASD and to describe a family-centered collaborative approach to
      developing social stories and comic strip conversations. The results of
      intervention employing an A-B design are reported for two case vignettes.
      Clinical implications, limitations of the available data, and potential factors
      contributing to outcome variability are discussed.

PMID- 16440245
TI  - Executive functions: a discussion of the issues facing children with autism
      spectrum disorders and related disorders.
AB  - The interest and attention devoted to executive functions has grown steadily in
      the last several decades. The concept and definitions of executive functions and
      their association with certain disorders such as autism spectrum disorders (ASD)
      and overall cognitive, social, emotional, and behavioral functioning are
      important knowledge areas for those working in education, health, and mental
      health-related fields. It is particularly important for providers to have an
      understanding of the basic issues related to assessment and remediation of
      executive dysfunction. This article briefly addresses the background, current
      definitions, research, and some intervention options associated with executive
      functions. The intent is to present a foundation for encouraging additional
      research on the issues relevant to this important topic.

PMID- 16440246
TI  - [Geriatric urology -- tumour diseases].
AB  - Due to demographic developments malignancies of urogenital origin will gain
      increasing importance. The urologist will face a growing group of patients with
      co-morbidities and functional disabilities as these neoplasms increase with age.
      Optimisation of peri-interventional management successfully reduces the risks of
      surgery. Integration of taxane-based cytostatic regimes achieves a prolongation
      of survival in hormone-refractory metastatic prostatic cancer. The introduction
      of gemcitabine in the management of malignancies of the bladder seems to have
      reduced toxicity while maintaining anti-tumour activity in comparison to MVAC.
      The role of haematopoetic growth factors remains to be defined in urologic
      malignancies - increasing dose intensity for better activity or reduction of
      toxicity. Individualisation of treatment requires early cooperation of the
      urologist, the oncologist and the geriatrician for an optimal outcome.

PMID- 16440247
TI  - [Sealing of percutaneous nephrolithotomy access after complete stone removal with
      a hemostyptic gelatin powder (Spongostan)].
AB  - PURPOSES: Parallel to the pilot project of Lee et al. which was published in
      February 2004, we also considered the possibility to seal the percutaneous
      nephrolithotomy (PCNL) access after complete stone removal via the local amplatz
      sheath. We started our project with the aims of increasing postoperative patient
      comfort, minimizing the risk of bleeding, and reducing postoperative cost and
      length of the hospital stay by performing this minimally invasive technique in 7
      patients with medium stone burden. MATERIALS AND METHODS: All patients were
      treated by removing stones via a working channel passing through the lower pole
      calix. After complete stone removal a hemostyptic gelatin powder (Spongostan,
      Johnson & Johnson) was prepared to a doughy paste, some drops of contrast medium
      were added and the whole material was introduced through the amplatz sheath into
      the working channel under imaging control. Imaging-controlled insertion of the
      doughy gelatin clot through the amplatz sheath into the parenchymal part of the
      channel alone resulted in immediate hemostasis in all patients. The amplatz
      sheath was retracted over a 28 Fr. rectal tube which was used to push the gelatin
      forward. There was no need for an additional tamponade of the renal fat capsule
      or the abdominal wall. After 2 minutes when no channel bleeding was apparent, the
      skin sutures were placed. RESULTS: Bleeding of the nephrostomy tract did not
      occur in any of the 7 patients. Average operating time was 50 minutes which was
      not significantly reduced by performing the new procedure. However, the hospital
      stay was reduced by 2 days. Two of the patients showed a single fever episode
      during the second postoperative evening. All patients presented with steady
      postoperative laboratory values without evidence of bleeding. Free urinary flow
      from the collecting system was controlled by means of ultrasound and urography.
      CONCLUSIONS: Similar to the recent usage of FloSeal/Baxter reported by Lee et al.
      we can confirm very reliable and immediate hemostasis using a pasty preparation
      of Spongostan (Johnson and Johnson) gelatin powder which was classified as being
      less toxic by the FDA in 2003 due to the lack of glutaraldehyde and bovine
      thrombin. Therefore, tubeless PCNL can be used for complete percutaneous
      clearance of stones without bleeding.

PMID- 16440248
TI  - [Success rates of two-layer, microsurgical vasovasostomy. Results from a patient
      questionnaire and comparison with one-layer technique].
AB  - Vasovasostomy is the most commonly performed procedures in the therapy for
      occlusive azoospermia after vasectomy. In our clinic the two-layer microsurgical
      technique (DL VVST) is considered to be the gold standard. We have examined the
      results of DL VVST by means of a questionnaire and compared them with those of
      the monolayer technique (ML VVST). MATERIALS AND METHOD: In the period from 1996
      to 2001, a microsurgical DL VVST with 10 x 0 Prolene sutures under the operation
      microscope was performed in 141 patient. Aspects of the operation, social aspects
      and postoperative results (results of spermiogram, birth rates) were assessed by
      means of a questionnaire. The results were compared with those of a historical
      patient collective who had undergone a modified monolayer VVST with 7 x 0 Prolene
      (n = 64). RESULTS: The questionnaire could be sent to 90/141 patients, the
      response rate was 63/90 (70 %). The time interval between vasectomy and VVST was
      on average 9.5 years. The patency rate was 86 %, the birth rate 24 %. Severe or
      moderately sever complications did not occur. In the historical patient
      collective, the average occlusion interval was 6.9 years. The patency rate in
      these patients in whom the VVST was performed merely under the loupe and in a
      monolayer technique was 87 %, the pregnancy rate 48 %. CONCLUSION: The highly
      positive results of VVST with pregnancy rates > 80 % from earlier publications
      could not be reproduced. According to our results, the two-layer VVST does not
      afford better results than the monolayer technique.

PMID- 16440249
TI  - [Frasier syndrome: a rare syndrome with WT1 gene mutation in pediatric urology].
AB  - INTRODUCTION: Frasier syndrom is an autosomal dominant, hereditary disease
      characterized by nephropathy, gonadal dysgenesis and risk of gonadal blastoma in
      early childhood. To date, in many patients with Frasier syndrome WT1 mutations
      have been found, occurring exclusively as germ-line mutations of the alternative
      splicing donor site in intron 9. A Wilms tumor is seen only rarely in this
      clinical entity. In the present paper we describe the clinical course of a
      patient with Frasier syndrome confirmed by molecular genetic analysis. CASE
      REPORT: Our patient with Frasier syndrome as confirmed by molecular genetic
      analysis is now 19 years old. The patient became dependent on dialysis due to
      nethropathy in the form of focal sclerosing glomerulonephritis and terminal renal
      insufficiency. A kidney transplantation in the left iliac fossa together with new
      implantation of the ureter according to Dodson. For prophylactic reasons on
      account of the high risk of gonadal blastoma associated with the disease and
      sonographically detected microlithiasis in both testicles we performed one year
      later an inguinal castration. Histology revealed the picture of a severe tubular
      testicular atrophy with arrested spermatogenesis and focal intratubular germ-line
      neoplasia. CONCLUSIONS: This case report shows that, besides our already
      published series with Denys-Drash syndrome, WT1 mutations may also be associated
      with the so-called Frasier syndrome. For children with Frasier syndrome confirmed
      by molecular genetic analysis and loss of function of the testicles, we recommend
      performance of a prophylactic castration. We also suggest that phenotypical
      female patients with focal sclerosing glomerulonephritis be examined for WT1
      mutations.

PMID- 16440252
TI  - [The position of the emergency physician in the emergency medical service].
AB  - The participation of emergency physicians guarantees the quality of a modern
      emergency medical service (EMS). Within the scope of cost savings in health-care
      system, it is questioned whether emergency medical services in the future can be
      managed without emergency physicians. Deficits of structure and qualitaty of the
      emergency physician service are raised objections. Recent studies have shown that
      preclinical care carried out by an emergency physician assure better results. An
      ongoing improvement in the quality of care should be achieved by the introduction
      of the new professional training for physicians "emergency medicine". In a direct
      comparison of two emergency medical services, one with emergency physicians, one
      only with paramedics it could be demonstrated that the integration of emergency
      physicians will increase the rate of patients, whose vital status could be
      improved by more than 20 %. The rate of patients discharged from hospital after
      cardiopulmonal resuscitation is 3 fold higher than in a rescue service without
      emergency physicians. However this improvement of quality of care by physicians
      is linked to higher financial charges. Another aspect supporting the obligatory
      employment of emergency physicians in Germany is the jurisdiction guaranteeing
      the right of the patient to receive advanced medical treatment only by
      (emergency) physicians.

PMID- 16440250
TI  - [Tuberculous orchiepididymitis and CNS complication].
AB  - INTRODUCTION: Hydrocephalus as a complication of tuberculous orchiepididymitis is
      extremely rare. In this reported case, hydrocephalus was the consequence of a
      disseminated tuberculous process. CASE REPORT: A 28-year-old man was treated for
      a left-sided orchiepididymitis. He developed the signs of increased intracranial
      pressure. Computer tomography (CT) of the brain showed a hydrocephalus. The
      diagnostics that followed confirmed disseminated tuberculosis (Tbc). CONCLUSIONS:
      Urogenital system is at the present rarely affected by Tbc. Especially rare is
      disseminated Tbc, which affects at the same time three different organ systems.
      Disseminated Tbc presented with many different but non-specific clinical
      symptoms, sometimes mimicking neoplasm. This makes diagnosis and therapy more
      difficult. We point out that in any case of orchiepididymitis not responding to
      standard antimicrobial therapy Tbc must be taken into consideration as the one of
      the differential diagnostic possibilities.

PMID- 16440253
TI  - [Preclinical diagnosis of traumatic paraplegia or tetraplegia -- a prospective
      study in 100 patients].
AB  - OBJECTIVE: To avoid neurological deterioration, traumatic spinal cord injury has
      to be recognized as early as possible. Aim of the study was to analyze
      alterations of the neurological level of injury in the preclinical interval.
      METHODS: In a prospective observational study the clinical diagnoses of 100
      patients referred to the Swiss Paraplegic Centre in Nottwil, Switzerland, were
      compared to the preclinical diagnoses. RESULTS: In 12 patients we observed
      neurological deterioration for more than 2 spinal segments. Six of these patients
      had been diagnosed preclinically with paraplegia at a neurological level of T4 or
      T5, whereas the evaluation in the hospital showed cervical spinal cord injury and
      tetraplegia. CONCLUSION: Possible reasons for this neurological deterioration can
      be secondary damages of the nervous tissue due to vascular, metabolic or
      biochemical mechanisms, transportation trauma or insufficient preclinical
      diagnostics. There is no evidence for a higher risk of secondary tissue damage
      for patients with cervical spinal cord injury. None of the six patients had
      additional injuries of the spinal cord or the vertebral column in the thoracic
      region, therefore transportation trauma is also unlikely. It is more likely that
      preclinical diagnoses were incorrect, what could have been avoided by consequent
      sensory and motor testing at the upper extremities.

PMID- 16440254
TI  - [Retrospective analysis of neurological patients on a medical intensive care
      unit].
AB  - OBJECTIVE: The aim of this study was to evaluate number and kind of neurological
      patients in comparison with other patients on a medical ICU. METHODS: Over a
      period of one year, all neurological intensive care patients on a medical ICU
      were evaluated according to age, sex, diagnosis, mortality, diagnostic methods,
      ventilation and referral to other hospitals and general wards. RESULTS:
      Comparable to a specialist neurological ICU a wide spectrum of neurological
      diseases could be observed on an interdisciplinary ICU. In comparison to other
      patient groups, patients with neurological disease had a higher rate of
      ventilation, a longer hospital stay and a higher mortality. CONCLUSION: Our data
      also demonstrate the relevant amount of neurological patients (19 % measured by
      bed assignment) in comparison to all patients, and the specific neurological
      procedures were applicable on a medical/interdisciplinary ICU. A higher interest
      for neurological patient on a medical ICU would therefore be essential.

PMID- 16440255
TI  - [Anaesthesiological management in orthotopic liver transplantation -- results of
      a survey].
AB  - OBJECTIVE: Since there is no therapeutical standard for the anaesthesiological
      approach during liver transplantation (LTX) in Germany at the moment, we have
      evaluated the current anaesthesiological procedures during LTX. METHODS: All
      departments of anaesthesiology (n = 24) cooperating with transplantation centers
      in Germany received a questionnaire via mail regarding following complexes:
      anaesthesiological methods, anaesthetics, blood components therapy, perioperative
      monitoring, supportive cardiovascular therapy and staff. RESULTS: The answers (n
      = 16) showed following results: Balanced anaesthesia with continuous application
      of opioids was the standard method (80 %). Different volatile anaesthetics as
      well as different opioids were used, isoflurane (66.7 %) and fentanyl (53.3 %)
      were the most common. Veno-venous bypass was never or occasionally used (86.7 %).
      The differentiated use of catecholamines, based on discussions in the last years,
      was also reflected in the results. Dobutamine/noradrenaline as combination seemed
      to be the first choice (46.7 %). Whereas there was an accordance with the
      employment of blood components, there was a large variation in the effectively
      applied blood products. Aprotinin was given in 60 % of all clinics occasionally,
      in 20 % every time and in 20 % aprotinine was never used. In most departments >
      or = 2 anaesthesiologists (80 %) and 1 nurse (53.3 %) were needed for
      intraoperative observation. Postoperative medical attendance was provided on
      anaesthesiological as well as surgical guided intensive care units (ICU).
      Generally accepted was an early extubation after arrival at the ICU (86.7 %).
      CONCLUSION: Even though there was a consensus in the anaesthesiological approach
      during LTX some departments still use different procedures. This is the first
      study that will give a basis for discussion of anaesthesiological approaches
      during LTX.

PMID- 16440256
TI  - Sepsis -- an ever new challenge.

PMID- 16440257
TI  - [From Roger Bone to PIRO].

PMID- 16440258
TI  - [Treatment of sepsis with antibiotics].

PMID- 16440259
TI  - [Surgical focal treatment].

PMID- 16440260
TI  - [Supportive treatment measures in severe sepsis].

PMID- 16440261
TI  - [Adjunctive treatment of sepsis].

PMID- 16440262
TI  - [Epidemiology, economy and practice -- results of the German study on prevalence
      by the competence network sepsis (SepNet)].

PMID- 16440263
TI  - NICE Technology Appraisal No 84.

PMID- 16440265
TI  - [Efficacy of a cognitive-behavioral program with pharmacological support to
      achieve smoking cessation].
AB  - BACKGROUND AND OBJECTIVE: In Germany over 30% of the population are smokers. Only
      very few smokers succeed in giving up smoking, because of the addictive nature of
      nicotine use. The objective of the present study was to evaluate a smoking
      cessation program which was recently established at a tertiary care clinic.
      PATIENTS AND METHODS: The median age of the 275 participants was 45.5 years;
      60.4% of participants were female. Participants had tobacco dependence of 5.1
      (Fagerstrom scale). The cognitive-behavioral smoking cessation program
      implemented in this clinic consisted of 8 sessions. Pharmacological support was
      recommended. A standardized evaluation was carried out after 6 and 12 months.
      RESULTS: All 275 smokers took part in the program over a period of 21 months. At
      the end of the course, 72% of participants had become non-smokers, after 6 months
      37.6% and after 12 months 27.1% had stopped smoking. Those who have not yet been
      evaluated 12 months after the end of the program demonstrated a point prevalence
      of 45.7% after 6 months. The cigarette consumption of participants who were
      smoking at the end of the course was reduced to less than half. 6 months later
      they smoked an average of 18.0 cigarettes /day; 12 months after ending the
      course, 19.0 /day were consumed (p<0,001). Costs of about 250 Euro per gained
      life year were approximated. CONCLUSION: It is possible to establish a smoking
      cessation program at a large clinic. The results correspond to international
      published experiences and confirm that such a program is efficacious and cost
      effective.

PMID- 16440264
TI  - [Continuous interscalenic nerve block in a 3 year old child after amputation of
      upper extremity].
AB  - Amputations of extremities, especially in the childhood, impose high demands on
      the perioperative management. Apart from the intraoperative care of these
      children, the postoperative pain therapy has to do one's utmost in the avoidance
      of the development of phantom limb pain, which can, especially in the childhood,
      be associated with far reaching psychological consequences. We report the case of
      a 3-year old boy who had to undergo exarticualtion of his left arm due to an
      osteosarcoma of the humerus. The perioperative pain management was performed by a
      preoperatively placed interscalene catheter and infusion of 0.2 % ropivacaine.
      Within the first six days postoperatively complete pain relief could be ensured
      with this analgetic regimen.

PMID- 16440266
TI  - [Acute femoral artery thrombosis after thrombin injection of a pseudoaneurysm].
AB  - HISTORY: A 64-year old woman was admitted because of unstable angina pectoris.
      The coronary angiogram revealed two-vessel coronary disease with predominantly
      subtotal stenosis of the right coronary artery, which was treated by primary
      coronary stenting. The post-interventional clinical course after closure of the
      right femoral artery was complicated by the development of a complex
      pseudoaneurysm: its ultrasound-guided compression was unsuccessful.
      INVESTIGATIONS: The clinical findings included a marked superficial hematoma in
      the right groin without any evidence of an abscess, confirmed by color duplex
      ultrasonography. TREATMENT AND COURSE: 24 hours later a successful percutaneous
      ultrasound-guided thrombin injection of the pseudoaneurysm was performed without
      any problems regarding the injection into the aneurysm. A small area within the
      aneurysm remained perfused and was treated by additional ultrasound-guided
      compression. A few minutes after the compression complete thrombosis of the right
      superficial femoral artery occurred with acute critical ischemia of the right
      leg, probably due to leakage of thrombin into the femoral artery at the sheath
      puncture. The immediate therapy, including interventional recanalization of the
      right femoral superficial artery and subsequent fibrinolysis, produced a complete
      reperfusion of the right femoral superficial and popliteal artery. The
      fibrinolytic therapy resolved the thrombosis of the pseudoaneurysm. The remainder
      of the perfused pseudoaneurysm was treated surgically after one week without
      problems. CONCLUSION: This case demonstrates a so far rarely published
      complication of the displacement of thrombin from an intervention ally treated
      pseudoaneurysm into the right superficial femoral artery through a broad compound
      channel after ultrasound-guided compression.

PMID- 16440268
TI  - [Clinical implications of meningococcal disease].

PMID- 16440269
TI  - [Bortezomib].

PMID- 16440270
TI  - [Differential diagnosis of platelet disorders].
AB  - Platelet disorders frequently represent a cause of bleeding disorders with a late
      manifestation and spontaneous bleeding. Disturbances of cellular hemostasis can
      be of quantitative nature due to an altered production or destruction of
      platelets. Qualitative disturbances can be associated with defects of adhesion,
      secretion or degranulation. Drug induced reactions, inflammatory processes and
      autoimmune reactions are the most frequent underlying disorders. Even a late
      manifestation, however, does not exclude congenital disorders. In the
      differential diagnosis of thrombocyte disorders the anamnestic analysis of the
      clinical circumstances of manifestation, of a family background and potentially
      interfering drugs are of central importance. Template bleeding time, aggregometry
      and flow cytometry are complementary methods for the characterization of
      functional defects. First of all, a von Willebrand syndrome as the most frequent
      congenital form of a mucocutaneous bleeding pattern needs to be excluded. The
      clinical context is very important in the analysis of disturbances of platelet
      turnover. Reticulated platelets allow the quantitative assessment of reduced
      production or increased destruction. Platelet indices, morphological assessment
      of blood and bone marrow and immunological tests allow the pathogenetical
      classification of thrombocytopenia. Idiopathic thrombocytopenia (ITP) is a
      frequent diagnosis by exclusion. The analysis of glycoprotein expression and the
      genetic characterization of suspected congenital defects are only performed in
      selected cases. Clinical and laboratory assessment are complementary in the
      discrimination of secondary forms of thrombosis from clinically relevant clonal
      disturbances.

PMID- 16440271
TI  - [Diagnosing malnutrition in the elderly].
AB  - The concept of malnutrition in the geriatric population describes a deficient
      state of energy and nutrient intake with harmful clinical consequences. Despite
      of having a significant effect on morbidity and mortality, there are no generally
      accepted criteria for diagnosing malnutrition in the elderly. With increasing age
      the general recognition of the nutritional status becomes more important for the
      diagnosis of malnutrition than isolated parameters. Recording a patient"s history
      must include any weight loss and changes in appetite. Reasons for a diminished
      nutritional intake must be explored systematically as well. As part of physical
      examination one has to pay attention to clinical signs of malnutrition (general
      muscular atrophy, loss of subcutaneous fat) and to signs of micronutrient
      deficiencies. The documentation of oral intake can supply important evidence for
      deficient intake of energy and nutrients. Of special relevance among
      anthropometric values are a BMI of less than 20 kg/m and calf circumference of
      less than 31 cm. Individual follow-up data are superior to isolated measurements
      Laboratory diagnostic tests (for example albumin) are of minor importance for the
      diagnosis of malnutrition because of their low specificity. As a consequence of
      unsolved methodical problems, bioelectrical impedance analysis can currently be
      recommended only to those who are experienced with this method and its
      limitations. Screening and assessment tools like Mini Nutritional Assessment
      (MNA) and Nutritional Risk Screening(NRS) are helpful for a quick and simple
      identification of malnourished patients and those who are at risk. The MNA is
      especially applicable for people who live independently and for cooperative
      residents of nursing homes. The NRS is a valuable alternative for hospital
      patients and those unable to cooperate. Screening for malnutrition should be
      routine practice in the elderly population, especially for those at high risk for
      it like in hospitals and in nursing homes.

PMID- 16440272
TI  - [Contribution of acidity using disguise or glasses?].

PMID- 16440273
TI  - [Complications of diagnostic laparoscopy . From this journal 1/2005].

PMID- 16440274
TI  - [Complications of diagnostic laparoscopy].

PMID- 16440275
TI  - The plant as a model.

PMID- 16440276
TI  - Molecular systematics is not genetics.

PMID- 16440277
TI  - Plant resistance versus animal immunity: the faithful divorce.

PMID- 16440278
TI  - The impact of genetically modified crops on soil microbial communities.
AB  - Genetically modified (GM) plants represent a potential benefit for
      environmentally friendly agriculture and human health. Though, poor knowledge is
      available on potential hazards posed by unintended modifications occurring during
      genetic manipulation. The increasing amount of reports on ecological risks and
      benefits of GM plants stresses the need for experimental works aimed at
      evaluating the impact of GM crops on natural and agro-ecosystems. Major
      environmental risks associated with GM crops include their potential impact on
      non-target soil microorganisms playing a fundamental role in crop residues
      degradation and in biogeochemical cycles. Recent works assessed the effects of GM
      crops on soil microbial communities on the basis of case-by-case studies, using
      multimodal experimental approaches involving different target and non-target
      organisms. Experimental evidences discussed in this review confirm that a
      precautionary approach should be adopted, by taking into account the risks
      associated with the unpredictability of transformation events, of their
      pleiotropic effects and of the fate of transgenes in natural and agro-ecosystems,
      weighing benefits against costs.

PMID- 16440279
TI  - Worthy heir or treacherous patricide? Konrad Lorenz and Jakob v. Uexkull.
AB  - The biologist Jakob v. Uexkull is often seen as the preceptor of modern
      behavioral theory, who lastingly influenced Konrad Lorenz in particular.
      Nevertheless, Uexkull has been highly inadequately received by the school Lorenz
      founded. This neglect of Uexkull's works resulted because Lorenz and Uexkull came
      into contact at a time when the biological sciences were sundered by a deep
      ideological division. On the one side stood the Darwin-rejecting Neo-Vitalists
      (for example Uexkull), on the other side were the Neo-Darwinists (for example
      Lorenz). After Vitalism was overcome as a consequence of the Evolutionary
      Synthesis, Darwinists who had taken an intermittent interest in Vitalists and
      their theories could now only distance themselves completely from earlier ideas.
      This went not only for biologists and behavioral researchers, but also for
      medical scientists. The emancipation from the starting points of their own
      science was so complete that, even decades later, when the earlier debates about
      Mechanism and Vitalism were long since historically outdated, behavioral research
      never investigated its own history.

PMID- 16440280
TI  - Ancon sheep: a now disproven example of macroevolution.
AB  - The Ancon breed of sheep provided, for decades, a critical support for the
      existence of major evolutionary changes or jumps called "sports." Putative
      examples of sports have been used as evidence of rapid macroevolution since
      Darwin first discussed the Ancon sheep mutation in 1859. Ancon sheep had very
      short legs that were considered an advantage for shepherds because the sheep were
      less likely to escape over fences. Many textbooks and articles implied that the
      breed was an example of how a major new trait could evolve in a single
      generation. The Ancon sheep example has been used both to prove gradual Darwinism
      and also to argue for rapid evolution as opposed to gradualism. It now is
      recognized that Ancon sheep resulted from genetic diseases, and that they usually
      suffered from achondroplasia. The so-called new breed had so many major health
      problems that the condition caused the breed's extinction decades ago, yet was
      mentioned in textbooks as evidence for evolutionary jumps as recently as 2005.

PMID- 16440281
TI  - Correlation among phenotypical and molecular techniques in comparing ascomycetous
      yeast type strains.
AB  - Different phenotypical or molecular techniques can be used to describe and
      classify microorganisms for taxonomic, phylogenetic or genetic purposes. In yeast
      taxonomy the official hierarchic classification, based on morphological and
      physiological characters, is used together with more convenient molecular
      techniques such as the DNA sequencing. The question on whether these procedures
      produce coherent classifications is critical both to interpret taxonomic data
      consistently and to outline species correctly. In this paper, a set of type
      strains from the major genera of the budding hemiascomycetes yeast is examined
      with a series of physiological and molecular techniques, widely employed in
      taxonomy, in order to compare the among-strains correlations obtained with
      different methods. Results showed that the level of correlation among different
      techniques is relatively low, showing that different classifications and species
      organization could be obtained with diverse approaches. This is particularly
      interesting, considering that the official description of the yeast species is
      based on characters different from those becoming increasingly popular in the
      routine identification.

PMID- 16440282
TI  - A fundamental plant evolutionary problem: the origin of land-plant sporophyte; is
      a new hypothesis possible?
AB  - The origin of the sporophyte in land plants represents a fundamental phase in the
      plant evolution. Today this subject is controversial and, in my opinion, scarcely
      considered in our textbooks and journals of botany, in spite of its importance.
      There are two conflicting theories concerning the origin of the alternating
      generations in land plants: the "antithetic" and the "homologous" theory. These
      have never been fully resolved. The antithetic theory maintains that the
      sporophyte and gametophyte generations are fundamentally dissimilar and that the
      sporophyte originated in an ancestor organism with haplontic cycle by the zygote
      dividing mitotically rather than meiotically, and with a developmental pattern
      not copying the developmental events of the gametophyte. The sporophyte
      generation was an innovation of critical significance for the land-plant
      evolution. By contrast, the homologous theory simply stated that a mass of cells
      forming mitotically from the zygote adopted the same developmental plan of the
      gametophyte, but giving origin to a diploid sporophyte. In this context, a very
      important question concerns the possible ancestor or ancestors of the land
      plants. Considerable evidences at morphological, cytological, ultrastructural,
      biochemical and, especially, molecular level, strongly suggest that the land
      plants or Embryophyta (both vascular and non-vascular) evolved from green algal
      ancestor(s), similar to those belonging to the genus Coleochaete, Chara and
      Nitella, living today. Their organism is haploid for most of their life cycle,
      and diploid only in the zygote phase (haplontic cycle). On the contrary, the land
      plants are characterized by a diplo-haplontic life cycle. Several questions are
      implied in these theories, and numerous problems remain to be solved, such as,
      for example, the morphological difference between gametophyte and sporophyte
      (heteromorphism, already present in the first land plants, the bryophytes), and
      the strong gap existing between these last with a sporophyte dependent on the
      gametophyte, and the pteridophytes having the gametophyte and sporophyte
      generations independent. On the ground of all of the evidences on the ancestors
      of the land plants, the antithetic theory is considered more plausible than the
      homologous theory. Unfortunately, no phylogenetic relationship exists between
      some green algae with diplontic life cycle and the land plants. Otherwise,
      perhaps, it should be possible to hypothesize another scenario in which to place
      the origin of the alternating generations of the land plants. In this case, could
      the gametophyte be formed by gametes produced from the sporophyte, through their
      mitoses or a delayed fertilization process?

PMID- 16440283
TI  - Air and the origin of the experimental plant physiology.
AB  - It is well known that oxygen and carbon dioxide are two chemicals which enter the
      plant metabolism as nutrients. The bases of this nowadays obvious statement were
      placed in the 18th century by means of the works of ingenious naturalists such as
      Robert Boyle, Stephen Hales, Joseph Priestley, Jam Ingenhousz, Lazzaro
      Spallanzani and Theodore De Saussure. Till the end of the 17th century, the
      atmospheric air was considered as an ineffable spirit, the function of which was
      of physical nature. Boyle was the first naturalist to admit the possibility that
      respiration were an exchange of vapours occurring in the blood. Stephen Hales
      realised that air could be fixed by plants under the influence of solar light.
      Priestley showed that plants could regenerate the bad air making it breathable.
      Ingenhousz demonstrated that the green parts of plants performed the complete
      purification of air only under the influence of the light. Spallanzani discovered
      that plants respire and guessed that the good air (oxygen) originated from the
      fixed air (carbon dioxide). Finally, Theodore De Saussure showed that plants were
      able to adsorb carbon dioxide and to release oxygen in a proportional air. All
      these discoveries benefited of the results coming from investigations of scholars
      of the so-called "pneumatic chemistry" (Boyle himself, George Ernst Stahl, Joseph
      Black, Priestley himself, and many more others. But among all the eminent
      scientists above mentioned stands out the genius of Antoine Laurent Lavoisier,
      who revolutionised the chemistry of the 18th century ferrying it towards the
      modern chemistry.

PMID- 16440284
TI  - Why do we need signs in biological systems?
AB  - This paper addresses a fundamental question: Why are there sign-mediated
      interactions in biology? According to Polanyi, biological hierarchies are
      constituted through boundary conditions. I argue that signs, or more accurately
      the processes of signification, function as these boundary conditions. Moreover,
      based on general insights from the physics of computation, I argue that the
      organism cannot be computed directly from the DNA without the loss of critical
      information. In this context, signs as boundary conditions mediate the biological
      construction in a way that prevents the loss of information and destabilization
      of the DNA.

PMID- 16440285
TI  - Mating success of wild type and sepia mutants Drosophila melanogaster in
      different choice.
AB  - Mating behaviour of red-eyed (wt) and brown-eyed (sepia) Drosophila melanogaster
      was studied under light conditions. Mating success was directly observed in
      mating vials and techniques usually applied in the studies of sexual selection
      ("female choice" and "multiple choice"). The comparison of sexual activity of
      mutant and wild types clearly indicates that they are not equally successful in
      matings. Sepia eye colour mutation decreases sexual activity of Drosophila
      melanogaster males, influences the preference ability of females and decreases
      the number of progeny from homogamic mating of the se x se type, as well as from
      heterogamic copulations in which sepia females take part. Non-random mating of
      wild type males and sepia females (in "multiple-choice" situation), with
      genetically and phenotypically different individuals, could be another mechanism
      for conservation of genetic polymorphism in natural populations.

PMID- 16440286
TI  - [An unusual course of invasive infection due to nontoxinogenic strain of
      Corynebacterium diphtheriae.].
AB  - The authors report a case of complicated sepsis caused by nontoxigenic
      Corynebacterium diphtheriae biotype gravis in a young immunocompetent female with
      no predisposing factors. She acquired the infection from her boyfriend, an
      asymptomatic carrier of nontoxigenic strain. The primary site of infection and
      subsequent sepsis was not identified. The occurence and importance of carriage
      and invasive infections caused by nontoxigenic strains of Corynebacterium
      diphtheriae are discused.

PMID- 16440287
TI  - Symptomatic vascular dystonia in Celiac disease.

PMID- 16440288
TI  - The cyclotide family of circular miniproteins: nature's combinatorial peptide
      template.
AB  - The cyclotides are a recently discovered family of miniproteins that contain a
      head-to-tail cyclized backbone and a knotted arrangement of disulfide bonds. They
      are approximately 30 amino acids in size and are present in high abundance in
      plants from the Violaceae, Rubiaceae, and Cucurbitaceae families, with individual
      plants containing a suite of up to 100 cyclotides. They have a diverse range of
      biological activities, including uterotonic, anti-HIV, antitumor, and
      antimicrobial activities, although their natural function is likely that of
      defending their host plants from pathogens and pests. This review focuses on the
      structural aspects of cyclotides, which may be thought of as a natural
      combinatorial peptide template in which a wide range of amino acids is displayed
      on a compact molecular core made up of the cyclic cystine knot structural motif.
      Cyclotides are exceptionally stable and are resistant to denaturation via
      thermal, chemical, or enzymatic treatments. The structural features that
      contribute to their remarkable stability are described in this review.

PMID- 16440289
TI  - Higher neutrophil infiltration mediated by osteopontin is a likely contributing
      factor to the increased susceptibility of females to alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) is a major public health problem in the United
      States and women are known to be more susceptible to ALD. However, the precise
      mechanism for increased susceptibility of females to ALD is not completely
      understood. The present study is based on the hypothesis that induction of
      osteopontin (OPN), a matricellular protein, is the likely contributing factor for
      higher neutrophil recruitment in females during alcoholic steatohepatitis (ASH).
      ASH was induced in male and female Sprague-Dawley rats by feeding them a Lieber
      DeCarli diet containing ethanol (EtOH) for 6 weeks, followed by a single
      injection of lipopolysaccharide (LPS, 10 mg/kg, ip). Liver injury, measured by
      plasma transaminase elevations and confirmed by haematoxylin and eosin-stained
      liver sections, revealed approximately 25-fold higher liver injury in the female
      ASH model compared with the males. Although steatosis, necrosis, and neutrophil
      infiltration were evident in both male and female rats, hepatic neutrophilic
      necrotic foci were noted as early as 2 h after LPS injection in the EtOH-treated
      female rats. Hepatic neutrophil infiltration correlated with higher expression of
      cleaved (cOPN) and uncleaved OPN in the EtOH + LPS-treated female rats compared
      with the males. OPN secretion was localized predominantly in the biliary
      epithelium and females had significantly higher OPN mRNA than their male
      counterparts in the ASH model. The ability of OPN to attract neutrophils was
      further confirmed in vivo, in a peritonitis rat model, and by neutralizing OPN
      (nOPN) antibody experiments. Hepatic neutrophil infiltration was largely
      inhibited ( approximately 50%) by nOPN antibody. Flow cytometry experiments
      revealed OPN-mediated up-regulation of the CD11b neutrophil adhesion molecule. In
      conclusion, these data suggest that higher hepatic expression of OPN is the
      likely reason for higher and early hepatic neutrophil infiltration making females
      more susceptible to ALD during ASH.

PMID- 16440290
TI  - A gene expression signature that distinguishes desmoid tumours from nodular
      fasciitis.
AB  - Nodular fasciitis (NF) is a rapidly growing cellular mass composed of
      fibroblasts/myofibroblasts, usually localized in subcutaneous tissues, that
      typically undergoes fibrosis and almost never recurs. Desmoid tumours (DTs) are
      rare forms of fibroblastic/myofibroblastic growth that arise in deep soft
      tissues, display a propensity for local infiltration and recurrence, but fail to
      metastasize. Given that both entities are primarily fibroblastic/myofibroblastic
      lesions with overlapping histological features, their gene expression profiles
      were compared to identify differentially expressed genes that may provide not
      only potential diagnostic markers, but also clues as to the pathogenesis of each
      disorder. Differentially expressed transcripts (89 clones displaying increased
      expression in DTs and 246 clones displaying increased expression in NF) included
      genes encoding several receptor and non-receptor tyrosine kinases (EPHB3, PTPRF,
      GNAZ, SYK, LYN, EPHA4, BIRC3), transcription factors (TWIST1, PITX2, EYA2, OAS1,
      MITF, TCF20), and members of the Wnt signalling pathway (AXIN2, WISP1, SFRP).
      Remarkably, almost one-quarter of the differentially expressed genes encode
      proteins associated with inflammation and tissue remodelling, including members
      of the interferon (IFN), tumour necrosis factor (TNF), and transforming growth
      factor beta (TGF-beta) signalling pathways as well as metalloproteinases (MMP1,
      9, 13, 23), urokinase plasminogen activator (PLAU), and cathepsins. The
      observations provide the first comparative molecular characterization of desmoid
      tumours and nodular fasciitis and suggest that selected tyrosine kinases,
      transcription factors, and members of the Wnt, TGF-beta, IFN, and TNF signalling
      pathways may be implicated in influencing and distinguishing their fate.

PMID- 16440291
TI  - Differential expression of a gene signature for scavenger/lectin receptors by
      endothelial cells and macrophages in human lymph node sinuses, the primary sites
      of regional metastasis.
AB  - Sentinel lymph node biopsy for several cancers has shown that metastatic tumour
      cells are preferentially arrested in the lymph node sinuses. To study the
      molecular components of this sinusoidal trap, gene profiling of lymph node
      (sinuses) versus tonsil (no sinuses) was performed. Among other groups of
      molecules, an intriguing gene signature of scavenger and lectin-like receptors
      was identified. Nine of the 13 genes were preferentially expressed in sinusoidal
      cells by immunohistochemistry. Using stabilin-2 and monoclonal antibody 3A5 as
      exclusive endothelial cell (EC) and macrophage (Mvarphi) markers, respectively,
      lymph node sinusoidal ECs (stabilin-2+, LYVE-1+, DC-SIGNR+, MARCO+, stabilin-1+,
      MMR+) and sinusoidal Mvarphi (MMR+, DC-SIGN+, sialoadhesin+, CD163+, stabilin-1+
      ) showed distinct, but overlapping expression patterns of the signature molecules
      by double labelling immunofluorescence. The number of stabilin-1+ sinusoidal
      Mvarphi, however, varied considerably between samples, indicating
      turnover/differentiation dynamics in this sinusoidal cell population. In the
      hepatic sinuses, LYVE-1 and CD36 were strongly up-regulated on both sinusoidal
      ECs and Mvarphi, while DC-SIGNR and DC-SIGN were strongly down-regulated; in
      contrast to lymph node sinusoidal ECs, MARCO was confined to Mvarphi (Kupffer
      cells) in the liver sinuses. As Mvarphi are not present in the wall and lumen of
      splenic sinuses, splenic sinuses expressed a considerably reduced repertoire of
      scavenger/lectin receptors lacking sialoadhesin, CD36, CD163, and MARCO; in
      addition, DC-SIGNR was absent from splenic sinusoidal ECs, while DC-SIGN and
      thrombomodulin were strongly expressed. Interestingly, most of the signature
      molecules are known to mediate tumour cell adhesion in addition to their
      functions as scavenger or pattern recognition receptors. This study establishes a
      gene and tissue database platform to test the hypothesis that additive expression
      of the lymph node sinus signature genes in sinusoidal ECs and Mvarphi may
      contribute to selective tumour cell metastasis in lymph nodes and liver including
      organ-specific mechanisms, such as intraluminal retention or transmigration,
      while sparing the spleen.

PMID- 16440292
TI  - Development of 5-HT1A receptor radioligands to determine receptor density and
      changes in endogenous 5-HT.
AB  - [(18)F]FCWAY and [(18)F]FPWAY, analogues of the high affinity 5-HT(1A) receptor
      (5-HT(1A)R) antagonist WAY100635, were evaluated in rodents as potential
      radiopharmaceuticals for determining 5-HT(1A)R density and changes in receptor
      occupancy due to changes in endogenous serotonin (5-HT) levels. The in vivo
      hippocampus specific binding ratio [(hippocampus(uptake)/cerebellum(uptake))-1]
      of [(18)F]FPWAY was decreased to 32% of the ratio of [(18)F]FCWAY, indicating
      that [(18)F]FPWAY has lower affinity than [(18)F]FCWAY. The 5-HT(1A)R selectivity
      of [(18)F]FPWAY was confirmed using ex vivo autoradiography studies with 5
      HT(1A)R knockout, heterozygous, and wildtype mice.Pre- or post-treatment of awake
      rodents in tissue dissection studies with paroxetine had no effect on hippocampal
      binding of [(18)F]FCWAY or [(18)F]FPWAY compared to controls, indicating neither
      tracer was sensitive to changes in endogenous 5-HT. In mouse ex vivo
      autoradiography studies in which awake mice were treated with fenfluramine
      following the [(18)F]FPWAY, a significant decrease was not observed in the
      hippocampus specific binding ratios. In rat dissection studies with fenfluramine
      administered following [(18)F]FPWAY or [(18)F]FBWAY ([(18)F]-MPPF) in awake or
      urethane-anesthetized rats, no significant differences in the specific binding
      ratios of the hippocampus were observed compared to their respective controls.
      [(18)F]FPWAY and [(18)F]FBWAY uptakes in all brain regions were increased
      variably in the anesthetized group (with the greatest increase in the
      hippocampus) vs. the awake group, but were decreased in the fenfluramine-treated
      anesthetized group vs. the anesthetized group. These data are best explained by
      changes in blood flow caused by urethane and fenfluramine, which varies from
      region to region in the brain.

PMID- 16440293
TI  - Distributions of two gonadotropin-releasing hormone receptor types in a cichlid
      fish suggest functional specialization.
AB  - Gonadotropin-releasing hormone 1 (GnRH1) from the brain controls reproduction in
      vertebrates via a GnRH-specific receptor in the pituitary; however, other forms
      of GnRH are found in all species, suggesting additional roles for this family of
      peptides. GnRH action depends critically on the location of its cognate receptors
      in the brain. To understand the potential roles of additional GnRH forms, we
      localized two known GnRH receptor types in a cichlid fish, Astatotilapia burtoni,
      in which GnRH1 is socially regulated. Using in situ hybridization, we describe
      the mRNA expression pattern of these GnRH receptor (GnRH-R) subtypes in the
      brain, specifically with respect to GnRH-producing neurons. Our data suggest that
      following a gene duplication, the two GnRH receptors have evolved to serve
      different functions. The type 1 receptor (GnRH-R1) is expressed less widely than
      the type 2 receptor (GnRH-R2). Specifically, GnRH-R1 is expressed in groups of
      neurons in the telencephalon, preoptic area, ventral hypothalamus, thalamus, and
      pituitary. In contrast, GnRH-R2 is expressed in many more brain areas, including
      the olfactory bulb, telencephalon, preoptic area, hypothalamus, thalamus,
      midbrain, optic tectum, cerebellum, hindbrain, and pituitary. The specific
      distribution of GnRH-R2 suggests that the GnRH ligands may act via this receptor
      to influence behavior in A. burtoni. Moreover, only GnRH-R2 mRNA is colocalized
      in the three known groups of GnRH-containing neurons, suggesting that any direct
      feedback regulation of GnRH by itself must act through this receptor type. Taken
      together, these data suggest that the two GnRH receptor types serve different
      functional roles in A. burtoni.

PMID- 16440294
TI  - Immunogold localization of phocein in dendritic spines.
AB  - Phocein, a widely expressed intracellular protein involved in clathrin- and
      dynamin-dependent membrane dynamics, has been shown to interact with members of
      the striatin family of proteins, striatin, SG2NA, and zinedin. Immunogold
      labeling was performed to assess subcellular localization of phocein in neurons
      of the rodent cerebellar cortex and hippocampal Ammon's horn. Most of the phocein
      bound gold particles were located within dendritic thorns and spines of the
      cerebellar Purkinje cells and hippocampal pyramidal neurons, as observed
      previously for striatin in striatal neurons. The postsynaptic profiles containing
      phocein were engaged in asymmetric synapses with the main types of afferents in
      the cerebellum and in the hippocampus. In the cerebellum, phocein-bound
      immunogold particle numbers ranged from 1-20 in approximately 50% of the Purkinje
      cell spines. In these spines most of the immunogold particles were found in the
      neuroplasm ( approximately 70%) and on nonsynaptic plasma membrane domains and
      related structures such as endocytic-like profiles ( approximately 18%). As soon
      as the first postnatal week, phocein was detected in the Purkinje cell somatic
      and dendritic thorns making asymmetric synapses with climbing fibers. During the
      following weeks the protein was located in the dendritic spines, as observed in
      the adult molecular layer. Finally, double immunogold labeling revealed a
      distribution of phocein and SG2NA suggesting that the two proteins could interact
      in the Purkinje cell spines. The early postnatal expression of phocein, a protein
      involved in membrane dynamics, suggests that it may have functional relevance in
      dendritic remodeling during development and potentially in spine plasticity
      during adulthood.

PMID- 16440295
TI  - Transforming growth factor-beta and bone morphogenetic proteins: cooperative
      players in chick and murine programmed retinal cell death.
AB  - Transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP)
      are extracellular molecules known to mediate programmed cell death (PCD) in the
      developing retina. In the present study, we investigated the expression profiles
      and activity levels of ligands and receptors of the TGF-beta and BMP4 family
      during the physiological PCD periods of the developing chick and mouse retina and
      possible interactions of both proapoptotic molecules in mediating apoptosis in
      chick and murine retinal whole-mount cultures. Immunocytochemical double-labeling
      studies with the established ganglion cell marker Islet revealed overlapping
      expression patterns for TGF-beta and BMP4 ligands and receptors on the surface of
      retinal ganglion cells. The biphasic peak of activity and expression levels of
      TGF-beta and BMP4 ligands and receptors, revealed by Western blots and mink lung
      epithelial cell (MLEC) assays, coincided with the two main periods of retinal
      chick and murine PCD. In organotypic retinal cultures, we were able to increase
      apoptosis over basal levels by application of recombinant TGF-beta or BMP4.
      Double-factor treatment induced an additional increase of apoptosis, suggesting a
      cooperation of both proapoptotic pathways. A significant increase in the number
      of apoptotic cells in the ganglion cell layer was observed in a TUNEL staining of
      retinal whole mounts treated with recombinant TGF-beta or BMP4, suggesting a
      concerted action of both factors in triggering ganglion cell death. Blockage
      experiments revealed that both pathways do not interact at the ligand, receptor,
      or Smad protein level but converge at the transcriptional level of the TGF-beta
      immediate-early response gene TIEG and the transcriptional coactivator Gcn5.

PMID- 16440296
TI  - Projections of the sensory trigeminal nucleus in a percomorph teleost, tilapia
      (Oreochromis niloticus).
AB  - The sensory trigeminal nucleus of teleosts is the rostralmost nucleus among the
      trigeminal sensory nuclear group in the rhombencephalon. The sensory trigeminal
      nucleus is known to receive the somatosensory afferents of the ophthalmic,
      maxillar, and mandibular nerves. However, the central connections of the sensory
      trigeminal nucleus remain unclear. Efferents of the sensory trigeminal nucleus
      were examined by means of tract-tracing methods, in a percomorph teleost,
      tilapia. After tracer injections to the sensory trigeminal nucleus, labeled
      terminals were seen bilaterally in the ventromedial thalamic nucleus,
      periventricular pretectal nucleus, medial part of preglomerular nucleus, stratum
      album centrale of the optic tectum, ventrolateral nucleus of the semicircular
      torus, lateral valvular nucleus, prethalamic nucleus, tegmentoterminal nucleus,
      and superior and inferior reticular formation, with preference for the
      contralateral side. Labeled terminals were also found bilaterally in the
      oculomotor nucleus, trochlear nucleus, trigeminal motor nucleus, facial motor
      nucleus, facial lobe, descending trigeminal nucleus, medial funicular nucleus,
      and contralateral sensory trigeminal nucleus and inferior olive. Labeled
      terminals in the oculomotor nucleus and trochlear nucleus showed similar
      densities on both sides of the brain. However, labelings in the trigeminal motor
      nucleus, facial motor nucleus, facial lobe, descending trigeminal nucleus, and
      medial funicular nucleus showed a clear ipsilateral dominance. Reciprocal tracer
      injection experiments to the ventromedial thalamic nucleus, optic tectum, and
      semicircular torus resulted in labeled cell bodies in the sensory trigeminal
      nucleus, with a few also in the descending trigeminal nucleus.

PMID- 16440299
TI  - Visual adaptations in the night-active wasp Apoica pallens.
AB  - The apposition compound eye of the nocturnal polistine wasp Apoica pallens shows,
      in comparison to the closely related diurnal wasp Polistes occidentalis, specific
      adaptations to vision at low light intensities. When considering recent work on
      nocturnal and diurnal bees, general principles for dim-light vision in
      hymenopterans become evident: The rhabdom diameters in nocturnal bees and wasps
      are 4 times wider compared to their diurnal relatives, leading to wide receptive
      fields, which in turn account for a 25-fold higher optical sensitivity.
      Interestingly, the rhabdom diameters in both nocturnal bees and wasps measure 8
      mum, which may represent the maximum width for nocturnal hymenopteran apposition
      eyes. A ratio of 1.8 times larger eyes is present in the nocturnal bees and
      wasps, which in A. pallens is achieved by increasing the facet number, instead of
      enlarging the facets, as in nocturnal bees. Although this initially indicates
      spatial resolution to be important for the nocturnal wasp, the wide receptive
      fields of the rhabdoms will reduce its potentially high acuity. As the optical
      sensitivity alone cannot account for the 8 log units intensity difference between
      day and night, a possible role of neural summation within the first optic
      ganglion (lamina) of nocturnal hymenopterans is discussed.

PMID- 16440297
TI  - Targeting dopamine D2 and cannabinoid-1 (CB1) receptors in rat nucleus accumbens.
AB  - The nucleus accumbens (Acb) shell and core are essential components of neural
      circuitry mediating the reward and motor effects produced by activation of
      dopamine D2 or cannabinoid-1 (CB1) receptors. D2 receptors can form heterodimeric
      complexes with cannabinoid-1 (CB1) receptors and are also involved in control of
      the availability of both dopamine and endocannabinoids. Thus, the subcellular
      locations of D2 and CB1 receptors with respect to each other are implicit to
      their physiological actions in the Acb. We used electron microscopic
      immunocytochemistry to determine these locations in the Acb shell and core of rat
      brain. In each region, many neuronal profiles showed endomembrane and
      plasmalemmal distributions of one or both receptors. Approximately one-third of
      the labeled profiles were somata and dendrites, some of which showed overlapping
      subcellular distributions of D2 and CB1 immunoreactivities. The remaining labeled
      profiles were small axons and axon terminals containing CB1 and/or D2 receptors.
      Of the labeled terminals forming recognizable synapses, approximately 20% of
      those containing CB1 receptors contacted D2-labeled dendrites, while conversely,
      almost 15% of those containing D2 receptors contacted CB1-labeled dendrites.
      These results provide the first ultrastructural evidence that D2 and CB1
      receptors in the Acb shell and core have subcellular distributions supporting
      both intracellular associations and local involvement of D2 receptors in making
      available endocannabinoids that are active on CB1 receptors in synaptic neurons.
      These distributions have direct relevance to the rewarding and euphoric as well
      as motor effects produced by marijuana and by addictive drugs enhancing dopamine
      levels in the Acb.

PMID- 16440298
TI  - Structural basis for developmentally regulated changes in cadherin function at
      synapses.
AB  - Members of the cadherin family of calcium-dependent cell adhesion molecules can
      bind homophilically across central nervous system (CNS) synapses, but
      experimental evidence indicates the nature of their contribution to synapse
      structure and function changes over time. We asked whether changes in function
      correspond to differences in intrasynaptic distribution. Using quantitative
      immuno-electronmicroscopy, we determined where cadherins are localized within
      synapses at key developmental stages in cultured hippocampal neurons and in
      hippocampus in vivo. At 5-6 days in culture, when most synapses are newly formed,
      cadherins are regularly and evenly distributed at synaptic clefts throughout the
      active zone. In contrast, at 14 days, when the majority of synapses are
      comparatively mature, cadherin labeling concentrates in discrete clusters. Such
      clusters can occur at any place within or immediately surrounding synaptic
      clefts. To assess whether this change in distribution is unique to neurons grown
      in culture, we compared the distribution of cadherins in the CA1 region of
      hippocampus at postnatal days 2, 3 (P2-3) and in adult. Consistent with our
      observations in cultured neurons, synapses in P2-3 hippocampus most often exhibit
      cadherins distributed regularly throughout the cleft, while adult synapses show
      predominantly discrete concentrations at single sites. The early developmental
      pattern of cadherin distribution can also be detected at occasional synapses in
      adult tissue. Such synapses also have morphological features consistent with
      immature synapses, suggesting that intrasynaptic cadherin distribution is a
      feature that may distinguish synapse age.

PMID- 16440300
TI  - Amino-terminus domain of the androgen receptor as a molecular target to prevent
      the hormonal progression of prostate cancer.
AB  - Prostate cancer has a propensity to metastasize to the bone. Currently the only
      effective systemic treatment for these patients is androgen ablation therapy.
      However, the tumor will invariably progress to an androgen-independent stage and
      the patient will succumb to his disease within approximately 2 years. The
      earliest indication of hormonal progression is the rising titer of serum prostate
      specific antigen. Current evidence implicates the androgen receptor (AR) as a key
      factor in maintaining the growth of prostate cancer cells in an androgen-depleted
      state. Under normal conditions, binding of ligand activates the receptor,
      allowing it to effectively bind to its respective DNA element. However, AR is
      also transformed in the absence of androgen (ligand-independent activation) in
      prostate cells via multiple protein kinase pathways and the interleukin-6 (IL-6)
      pathway that converge upon the N-terminal domain of the AR. This domain is the
      main region for phosphorylation and is also critical for normal coregulator
      recruitment. Here we discuss evidence supporting the role of the AR, IL-6 and
      other protein kinase pathways in the hormonal progression of prostate cancer to
      androgen independence and the mechanisms involved in activation of the AR by
      these pathways. Receptor-targeted therapy, especially potential drugs targeting
      the N-terminal domain, may effectively prevent or delay the hormonal progression
      of AR-dependent prostate cancer.

PMID- 16440301
TI  - PECAM-1 isoform-specific activation of MAPK/ERKs and small GTPases: implications
      in inflammation and angiogenesis.
AB  - Platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) is expressed on the
      surface of endothelial cells (EC) and leukocytes. PECAM-1 plays an important role
      in endothelial-leukocyte and endothelial-endothelial cell-cell interactions. The
      anti-PECAM-1 antibody-mediated blockade of these interactions inhibits
      transendothelial migration (TEM) of leukocytes and angiogenesis. PECAM-1 may
      accommodate these processes through the regulation of cell adhesive and migratory
      mechanisms. How PECAM-1 regulates these dynamic processes remain unknown. Here we
      show that PECAM-1 transduces outside-in signals, which activate MAPK/ERKs and
      small GTPases. This occurs through PECAM-1-mediated formation of intracellular
      signaling complexes, Shc/Grb2/SOS1 and/or Crkl/C3G, which is initiated by PECAM-1
      engagement on the surface of leukocytes and/or EC. Src, SHP2, and alternative
      PECAM-1 pre-mRNA splicing play a regulatory role in these signaling events. Our
      findings reveal that PECAM-1 engagement on the cell surface can transduce
      "outside-in" signals and activate MAPK/ERKs and small GTPases, impacting both
      cadherin-mediated cell-cell and integrin-mediated cell-matrix interactions. Thus,
      we propose PECAM-1 is an important mediator of vascular barrier and regulator of
      leukocyte and EC adhesion and migration.

PMID- 16440302
TI  - Prostanoid pattern and iNOS expression during chondrogenic differentiation of
      human mesenchymal stem cells.
AB  - Availability of human chondrocytes is a major limiting factor regarding drug
      discovery projects and tissue replacement therapies. As an alternative human
      mesenchymal stem cells (hMSCs) from bone marrow are taken into consideration as
      they can differentiate along the chondrogenic lineage. However, it remains to be
      shown whether they could form a valid model for primary chondrocytes with regards
      to inflammatory mediator production, like nitric oxide (NO) and prostanoids. We
      therefore investigated the production of NO and prostanoids in hMSCs over the
      course of chondrogenic differentiation and in response to IL-1beta using primary
      OA chondrocytes as reference. Chondrogenic differentiation was monitored over 28
      days using collagen I, collagen II, and collagen X expression levels. Expression
      levels of inducible nitric oxide synthase (iNOS), levels of NO, and prostanoids
      were assessed using PCR, Griess assay, and GC/MS/MS, respectively. The hMSCs
      collagen expression profile during course of differentiation was consistent with
      a chondrocytic phenotype. Contrary to undifferentiated cells, differentiated
      hMSCs expressed iNOS and produced NO following stimulation with IL-1beta.
      Moreover, this induction of iNOS expression was corticosteroid insensitive. The
      spectrum of prostanoid production in differentiated hMSCs showed similarities to
      that of OA chondrocytes, with PGE2 as predominant product. We provide the first
      detailed characterization of NO and prostanoid production in hMSCs in the course
      of chondrogenic differentiation. Our results suggest that differentiated hMSCs
      form a valid model for chondrocytes concerning inflammatory mediator production.
      Furthermore, we propose that IL-1beta stimulation, leading to corticosteroid
      insensitive NO synthesis, can be used as a sensitive marker of chondrogenesis.

PMID- 16440303
TI  - Effects of cadmium on structure and enzymatic activity of Cu,Zn-SOD and oxidative
      status in neural cells.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      disease. Ten percent of the ALS patients are congenital (familial ALS), and the
      other 90% are sporadic ALS (SALS). It has been shown that mutations found in the
      Cu,Zn-SOD cause 20% of the familial ALS due to its low enzyme activity. We
      hypothesized that heavy metals may interfere the structure of Cu,Zn-SOD protein
      to suppress its activity in some of the SALS. In this study, we expressed and
      characterized the recombinant human Cu,Zn-SOD under various concentrations of
      Cu(2+), Zn(2+), and Cd(2+). By atomic absorption spectrophotometry, we
      demonstrated that adding of cadmium significantly increased the content of
      cadmium ion, but reduced its Zn(2+) content and enzyme activity of the Cu,Zn-SOD
      protein. The data of circular dichroism spectra demonstrated that the secondary
      structure of Cu,Zn-SOD/Cd is different from Cu,Zn-SOD, but close to apo-SOD. In
      addition to the effect of cadmium on Cu,Zn-SOD, cadmium was also shown to induce
      neural cell apoptosis. To further investigate the mechanism of neural cell
      apoptosis induced by cadmium, we used proteomics to analyze the altered protein
      expressions in neural cells treated with cadmium. The altered proteins include
      cellular structural proteins, stress-related and chaperone proteins, proteins
      involved in reactive oxygen species (ROS), enzyme proteins, and proteins that
      mediated cell death and survival signaling. Taken together, in this paper, we
      demonstrate that cadmium decreases the content of Zn(2+), changes the
      conformation of Cu,Zn-SOD protein to decrease its enzyme activity, and causes
      oxidative stress-induced neural cell apoptosis.

PMID- 16440304
TI  - Quantitative analysis of localization and nuclear aggregate formation induced by
      GFP-lamin A mutant proteins in living HeLa cells.
AB  - Although A-type lamins are ubiquitously expressed, their role in the tissue
      specificity of human laminopathies remains enigmatic. In this study, we generate
      a series of transfection constructs encoding missense lamin A mutant proteins
      fused to green fluorescent protein and investigate their subnuclear localization
      using quantitative live cell imaging. The mutant constructs used included the
      laminopathy-inducing lamin A rod domain mutants N195K, E358K, M371K, R386K, the
      tail domain mutants G465D, R482L, and R527P, and the Hutchinson-Gilford progeria
      syndrome-causing deletion mutant, progerin (LaA delta50). All mutant derivatives
      induced nuclear aggregates, except for progerin, which caused a more lobulated
      phenotype of the nucleus. Quantitative analysis revealed that the frequency of
      nuclear aggregate formation was significantly higher (two to four times) for the
      mutants compared to the wild type, although the level of lamin fusion proteins
      within nuclear aggregates was not. The distribution of endogenous A-type lamins
      was altered by overexpression of the lamin A mutants, coexpression experiments
      revealing that aberrant localization of the N195K and R386K mutants had no effect
      on the subnuclear distribution of histones H2A or H2B, or on nuclear accumulation
      of H2A overexpressed as a DsRed2 fusion protein. The GFP-lamin fusion protein
      expressing constructs will have important applications in the future, enabling
      live cell imaging of nuclear processes involving lamins and how this may relate
      to the pathogenesis of laminopathies.

PMID- 16440305
TI  - Fibroblast extracellular matrix gene expression in response to keratinocyte
      releasable stratifin.
AB  - Termination of wound-healing process requires a fine balance between connective
      tissue deposition and its hydrolysis. Previously, we have demonstrated that
      keratinocyte-releasable stratifin, also known as 14-3-3 sigma protein, stimulates
      collagenase (MMP-1) expression in dermal fibroblasts. However, role of
      extracellular stratifin in regulation of extracellular matrix (ECM) factors and
      other matrix metalloproteinases (MMPs) in dermal fibroblast remains unexplored.
      To address this question, large-scale ECM gene expression profile were analyzed
      in human dermal fibroblasts co-cultured with keratinocytes or treated with
      recombinant stratifin. Superarray pathway-specific microarrays were utilized to
      identify upregulation or downregulation of 96 human ECM and adhesion molecule
      genes. RT-PCR and Western blot were used to validate microarray expression
      profiles of selected genes. Comparison of gene profiles with the appropriate
      controls showed a significant (more than twofold) increase in expression of
      collagenase-1, stromelysin-1 and -2, neutrophil collagenase, and membrane type 5
      MMP in dermal fibroblasts treated with stratifin or co-cultured with
      keratinocytes. Expression of type I collagen and fibronectin genes decreased in
      the same fibroblasts. The results of a dose-response experiment showed that
      stratifin stimulates the expression of stromelysin-1 (MMP-3) mRNA by dermal
      fibroblasts in a concentration-dependent fashion. Furthermore, Western blot
      analysis of fibroblast-conditioned medium showed a peak in MMP-3 protein levels
      48 h following treatment with recombinant stratifin. In a lasting-effect study,
      MMP-3 protein was detected in fibroblast-condition medium for up to 72 h post
      removal of stratifin. In conclusion, our results suggest that keratinocyte
      releasable stratifin plays a major role in induction of ECM degradation by dermal
      fibroblasts through stimulation of key MMPs, such as MMP-1 and MMP-3. Therefore,
      stratifin protein may prove to be a useful target for clinical intervention in
      controlling excessive wound healing in fibrotic conditions.

PMID- 16440307
TI  - Antisense applications for biological control.
AB  - Although Nature's antisense approaches are clearly impressive, this Perspectives
      article focuses on the experimental uses of antisense reagents (ASRs) for control
      of biological processes. ASRs comprise antisense oligonucleotides (ASOs), and
      their catalytically active counterparts ribozymes and DNAzymes, as well as small
      interfering RNAs (siRNAs). ASOs and ribozymes/DNAzymes target RNA molecules on
      the basis of Watson-Crick base pairing in sequence-specific manner. ASOs
      generally result in destruction of the target RNA by RNase-H mediated mechanisms,
      although they may also sterically block translation, also resulting in loss of
      protein production. Ribozymes and DNAzymes cleave target RNAs after base pairing
      via their antisense flanking arms. siRNAs, which contain both sense and antisense
      regions from a target RNA, can mediate target RNA destruction via RNAi and the
      RISC, although they can also function at the transcriptional level. A
      considerable number of ASRs (mostly ASOs) have progressed into clinical trials,
      although most have relatively long histories in Phase I/II settings. Clinical
      trial results are surprisingly difficult to find, although few ASRs appear to
      have yet established efficacy in Phase III levels. Evolution of ASRs has
      included: (a) Modifications to ASOs to render them nuclease resistant, with
      analogous modifications to siRNAs being developed; and (b) Development of
      strategies to select optimal sites for targeting. Perhaps the biggest barrier to
      effective therapies with ASRs is the "Delivery Problem." Various liposomal
      vehicles have been used for systemic delivery with some success, and recent
      modifications appear to enhance systemic delivery, at least to liver. Various
      nanoparticle formulations are now being developed which may also enhance
      delivery. Going forward, topical applications of ASRs would seem to have the best
      chances for success. In summary, modifications to ASRs to enhance stability,
      improve targeting, and incremental improvements in delivery vehicles continue to
      make ASRs attractive as molecular therapeutics, but their advance toward the
      bedside has been agonizingly slow.

PMID- 16440306
TI  - LDL induces Saos2 osteoblasts death via Akt pathways responsive to a neutral
      sphingomyelinase inhibitor.
AB  - Atherosclerosis is epidemiologically associated with postmenopausal osteoporosis
      (OP) presumably by common etiologic factors, reflecting a state of co-morbidity
      in aging. Osteoblasts make a significant facet of this co-morbidity state. Since
      oxidized low-density lipoprotein (oxLDL) is a major factor in generation of
      vascular wall pathology, we examined the ability of native LDL (nLDL) and oxLDL
      to induce Saos2 osteoblasts growth arrest. OxLDL induced Saos2 cell death with
      morphological features of apoptosis that was inhibited mainly by caspase-9 and
      partially by caspase-3 but not by caspase-8 inhibitors. nLDL, like oxLDL, has
      induced cell death, where 60% (P = 0.00033) and 30% (P = 0.075, ns) of the cell
      death, respectively, could be inhibited by scyphostatin (a neutral
      sphingomyelinase [nSMase] inhibitor). Upon similar condition, nLDL inhibited the
      phosphorylation of Akt and two of its downstream targets, fork head receptor
      (FKHR) and glycogen synthase kinase-3 (GSK3). This is a pathway that stimulates
      cell survival and proliferation. nLDL has also induced an increase in the
      proapoptotic Bcl-Xs and it has diminished the potential antiapoptotic Src kinase
      activity. At the 4 h time-point, upon a substantial decrease in nLDL-induced Akt
      phosphorylation, scyphostatin has inhibited the reduction in FKHR and GSK3
      phosphorylation but inexplicably not that of Akt. Scyphostatin has also corrected
      the reduction in Src kinase activity. Taken together, the results indicate that
      nLDL has induced apoptosis in Saos2 osteoblasts by inactivation of the pathway
      downstream to Akt using nSMase, and by involvement of Src kinase. Inferring that
      caspase-9 was the main executioner (rather than caspase-8 and-3) in Saos2 cell
      death, indicates that the nSMase-induced release of ceramide, directly activated
      the intrinsic mitochondrial apoptotic pathway. With regard to the Akt
      inactivation by nLDL, Saos2 osteoblasts responded in an opposite fashion to the
      response reported by others, in macrophages.

PMID- 16440308
TI  - c-Jun kinase mediates expression of VEGF induced at transcriptional level by Rac1
      and Cdc42Hs but not by RhoA.
AB  - Tumour angiogenesis is mediated by increased levels of vascular endothelial
      growth factor (VEGF). We have studied the mechanism by which endogenous
      activation of Rho oncoproteins regulates VEGF expression in COS-7 and NIH3T3
      cells. We carried out transient and stable transfection with constitutively
      activated rhoA, rac1, and cdc42 mutants in COS-7 and NIH3T3 cells, respectively
      in the absence of external stimuli. Western blot and inmunohistochemistry assays
      of those cells revealed increased VEGF protein expression. Cotransfection with
      constitutively activated rhoA, rac1, and cdc42 mutants and a VEGF promoter
      reporter construct showed an increase in VEGF promoter transcriptional activity
      induced by Rho oncoproteins in COS-7 and NIH3T3. c-Jun kinase had been described
      as a MAPK involved in Rho oncoproteins pathways. Interestingly, we found that c
      Jun kinase chemical inhibition as well as transient transactivation assays using
      dominant negative c-Jun kinase mutant abolished the VEGF promoter transcriptional
      induction by Rac1 and Cdc42 but not by RhoA. These findings indicate that Rho
      oncoprotein endogenously activated regulates VEGF expression through a
      transcriptional mechanism, and that the c-Jun kinase activity is a mediator in
      the expression of VEGF induced by Rac1 and Cdc42 oncoproteins, but not of that
      induced by RhoA.

PMID- 16440309
TI  - Roles of MAP kinases in the regulation of bone matrix gene expressions in human
      osteoblasts by oscillatory fluid flow.
AB  - We investigated the effects of oscillatory flow in regulating the gene
      expressions of type I collagen (COL1, the main component of human bone tissues)
      and osteopontin (OPN, the key gene for calcium deposition) in human osteoblast
      like (MG-63) cells, and the roles of mitogen-activated protein kinases (MAPKs) in
      this regulation. The cells were subjected to oscillatory flow (0.5 +/- 4
      dyn/cm(2)) or kept under static condition for various time periods (15 min, 30
      min, 1 h, 2 h, 4 h, 8 h, and 16 h). Oscillatory flow caused significant up
      regulations of both COL1 and OPN gene expressions over the 16 h of study, and a
      transient activation of MAPKs was starting at 15 min and declining to basal level
      in 2 h. The flow-induction of COL1 was blocked by an ERK inhibitor (PD98059) and
      reduced by a JNK inhibitor (SP600125), whereas that of OPN was abolished by
      PD98059. Analysis of the cis-elements in the COL1 and OPN promoters suggests the
      involvement of transacting factors Elk-1 and AP-1 in the transcription
      regulation. The ERK inhibitor (PD98059) blocked Elk-1 phosphorylation, as well as
      COL1 and OPN gene expression. The JNK inhibitor (SP600125) abolished c-jun
      phosphorylation and COL1 expression. These results suggest that the flow
      induction of OPN was mediated through the ERK-Elk1-OPN pathway, and that COL1 was
      regulated by both the ERK-Elk1-COL1 and JNK-c-JUN-COL1 pathway.

PMID- 16440310
TI  - Calcyclin binding protein promotes DNA synthesis and differentiation in rat
      neonatal cardiomyocytes.
AB  - During cardiac muscle development, most cardiomyocytes permanently withdraw from
      the cell cycle. Previously, by suppressive subtractive hybridization, we
      identified calcyclin-binding protein/Siah-interacting protein (CacyBP/SIP) as one
      of the candidates being upregulated in the hyperplastic to hypertrophic switch,
      suggesting an important role of CacyBP/SIP in cardiac development. To show the
      importance of CacyBP/SIP during myoblast differentiation, we report here that
      CacyBP/SIP is developmentally regulated in postnatal rat hearts. The
      overexpression of CacyBP/SIP promotes the differentiation and DNA synthesis of
      H9C2 cells and primary rat cardiomyocytes, as well as downregulates the
      expression of beta-catenin. Besides, CacyBP/SIP promotes the formation of
      myotubes and multinucleation upon differentiation. To investigate the
      cardioprotective role of CacyBP/SIP in cardiomyocytes, a hypoxia/reoxygenation
      model was employed. We found that CacyBP/SIP was upregulated during myocardial
      infarction (MI) and hypoxia/reoxygenation. As a conclusion, CacyBP/SIP may play a
      role in cardiomyogenic differentiation and possibly protection of cardiomyocytes
      during hypoxia/reoxygenation injury.

PMID- 16440311
TI  - Collagen type I selectively activates ectodomain shedding of the discoidin domain
      receptor 1: involvement of Src tyrosine kinase.
AB  - The discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that is
      highly expressed in breast carcinoma cells. Upon binding to collagen, DDR1
      undergoes autophosphorylation followed by limited proteolysis to generate a
      tyrosine phosphorylated C-terminal fragment (CTF). Although it was postulated
      that this fragment is formed as a result of shedding of the N-terminal
      ectodomain, collagen-dependent release of the DDR1 extracellular domain has not
      been demonstrated. We now report that, in conjunction with CTF formation,
      collagen type I stimulates concentration-dependent, saturable shedding of the
      DDR1 ectodomain from two carcinoma cell lines, and from transfected cells. In
      contrast, collagen did not promote cleavage of other transmembrane proteins
      including the amyloid precursor protein (APP), ErbB2, and E-cadherin. Collagen
      dependent tyrosine phosphorylation and proteolysis of DDR1 in carcinoma cells
      were reduced by a pharmacologic Src inhibitor. Moreover, expression of a dominant
      negative Src mutant protein in human embryonic kidney cells inhibited collagen
      dependent phosphorylation and shedding of co-transfected DDR1. The hydroxamate
      based metalloproteinase inhibitor TAPI-1 (tumor necrosis factor-alpha protease
      inhibitor-1), and tissue inhibitor of metalloproteinase (TIMP)-3, also blocked
      collagen-evoked DDR1 shedding, but did not reduce levels of the phosphorylated
      CTF. Neither shedding nor CTF formation were affected by the gamma-secretase
      inhibitor, L-685,458. The results demonstrate that collagen-evoked ectodomain
      cleavage of DDR1 is mediated in part by Src-dependent activation or recruitment
      of a matrix- or disintegrin metalloproteinase, and that CTF formation can occur
      independently of ectodomain shedding. Delayed shedding of the DDR1 ectodomain may
      represent a mechanism that limits DDR1-dependent cell adhesion and migration on
      collagen matrices.

PMID- 16440312
TI  - Role of amino acids in translational mechanisms governing milk protein synthesis
      in murine and ruminant mammary epithelial cells.
AB  - The role of amino acids (AA) on translational regulation in mammary epithelial
      cells cultured under lactogenic conditions was studied. The rates of total
      protein synthesis and beta-lactoglobulin (BLG) synthesis in mouse CID-9 cells
      were 2.1- or 3.1-fold higher, respectively, than in their bovine L-1
      counterparts. Total AA deprivation or selective deprivation of Leu had a negative
      protein-specific effect on BLG synthesis that was more pronounced in bovine cells
      than in murine cells. Dephosphorylation of eukaryotic initiation factor 4E
      binding protein 1 (4E-BP1) and S6 kinase (S6K1) on Thr(389) but not on Ser(411)
      was also more prominent in bovine cells. Noteably, deprivation of Leu had a less
      marked effect on BLG synthesis and 4E-BP1 or S6K1 phosphorylation than
      deprivation of all AA. In AA-deprived CID-9 cells, Leu specifically restored BLG
      synthesis from pre-existing mRNA whereas AA also restored total protein
      synthesis. This restoration was associated with a more pronounced effect on 4E
      BP1 and S6K1 phosphorylation in bovine versus murine cells. Rapamycin
      specifically reduced Leu- and AA-stimulated BLG translation initiation in a dose
      dependent manner. A further reduction was observed for Leu-treated cells in the
      presence of LY294002, a PI3K (phosphatidylinositol 3-kinase) inhibitor, which
      also reduced total protein synthesis. These findings suggest that direct
      signaling from AA to the translational machinery is involved in determining the
      rates of milk protein synthesis in mammary epithelial cells.

PMID- 16440313
TI  - Plugs in nuclear pores: transcripts in early oocyte development identified with
      nanotechniques.
AB  - Throughout oogenesis, huge amounts of RNA are produced that are needed for early
      development. Early stages of oocyte development are characterized by high
      transcriptional activity whereas translation of maternal RNA dominates late
      stages. Nuclear pore complexes (NPCs), located in the nuclear envelope (NE),
      mediate bidirectional macromolecule exchange between the nuclear and cytosolic
      compartments including RNA export. Here, we report on structural correlates of
      this transport pathway at single NPC level. Using atomic force microscopy (AFM),
      we imaged the nucleoplasmic ("inner") surface of the NE of Xenopus laevis oocytes
      in different stages of development. We found that NPC frequency per nucleus
      increases with maturation. However, individual NPCs are more active in immature
      stages. In early stages, known for high transcriptional activity, we found nearly
      10% of NPC central channels plugged with a 400-800 kDa mass. In contrast, the
      incidence of plugged NPCs was below 1% in late oocyte stages. On-site RNA
      digestion led to a change in plug shape from prominent to flat while plug mass
      decreased by almost 20%. Quantitative AFM analysis revealed that RNase exposure
      reduced total nucleoplasmic NPC mass by about 58 and 25% in early and late stage
      oocytes, respectively. We conclude: (i) NPCs of immature oocytes are more active
      in RNA transport, (ii) Plugs identified at the nucleoplasmic entrance of NPC
      central channels represent ribonucleoproteins exiting the nucleus, (iii) RNA is a
      structural component of the NPC nanomachine.

PMID- 16440314
TI  - DNA sequences acting as binding sites for NM23/NDPK proteins in melanoma M14
      cells.
AB  - We isolated and analyzed by chromatin immunoprecipitation (ChIP) in viable M14
      cells DNA sequences bound to the antimetastatic protein nucleoside diphosphate
      kinase (NM23/NDPK) to shed some light on the nuclear functions of this protein
      and on the mechanism by which it acts in development and cancer. We assessed the
      presence of selected sequences from promoters of platelet-derived growth factor A
      (PDGF-A), c-myc, myeloperoxidase (MPO), CD11b, p53, WT1, CCR5, ING1, and NM23-H1
      genes in the cross-linked complexes. Quantitative PCR (Q-PCR) showed a
      substantial enrichment of the correlated oncosuppressor genes p53, WT1, ING1, and
      NM23-H1 in the immunoprecipitated (IP) DNA. This suggests that NM23/NDPK binding
      is involved in the transcription regulation of these genes. These results reveal
      new interactions that should help us to disclose the antimetastatic mechanism of
      NM23.

PMID- 16440315
TI  - Functional characterization of hNUDC as a novel accumulator that specifically
      acts on in vitro megakaryocytopoiesis and in vivo platelet production.
AB  - Human NUDC (hNUDC) has been previously described as a human homolog of a fungal
      nuclear migration protein. It is a multifunctional interactive protein that forms
      an association with the microtubule motor complex in a variety of cells. Our
      recent studies demonstrated that hNUDC could bind specifically to the
      thrombopoietin receptor (Mpl) and suggest a potential role for hNUDC in
      megakaryocytopoiesis and thrombopoiesis. The present study is designed to define
      its biological activity. We demonstrate that the recombinant hNUDC significantly
      increases megakaryocyte maturation in serum-free liquid-cultured human CD34(+)
      cells and stimulates colony formation in serum-free semi-solid cultures. Flow
      cytometry analyses also confirm the stimulatory effect of hNUDC on megakaryocyte
      polyploidization and in vitro platelet production. In vivo experiments further
      demonstrate that the administration of hNUDC substantially enhance the number of
      circulating platelets in normal mice.

PMID- 16440316
TI  - Gingival fibroblasts are better at inhibiting osteoclast formation than
      periodontal ligament fibroblasts.
AB  - Various studies indicate that periodontal ligament fibroblasts (PLF) have some
      similarities to osteoblasts, for example they have the capacity to induce the
      formation of osteoclast-like cells. Here, we investigated whether a second
      population of tooth-associated fibroblasts, gingival fibroblasts (GF), has
      similar osteoclastogenesis properties. PLF and GF were co-cultured with
      peripheral blood mononuclear cells (PBMC) in the presence and absence of
      dexamethasone and 1alpha,25dihydroxycholecalciferol (dex + vit D(3)) on plastic
      and on cortical bone slices. Tartrate resistant acid phosphatase (TRACP) positive
      multinucleated cells (MNCs) were more abundant in co-cultures with PLF than in GF
      PBMC co-cultures, more abundant on plastic compared to bone and more abundant in
      the presence of dex + vit D(3). In line with these findings was an inhibition of
      MNC formation and not inhibition of existing osteoclasts by medium conditioned by
      GF. We next investigated whether expression of molecules important for
      osteoclastogenesis differed between the two types of fibroblasts and whether
      these molecules were regulated by dex + vit D(3). OPG was detected at high levels
      in both fibroblast cultures, whereas RANKL could not be detected. Resorption of
      bone did not occur by the MNCs formed in the presence of either fibroblast
      subpopulation, suggesting that the fibroblasts secrete inhibitors of bone
      resorption or that the osteoclast-like cells were not functional. The incapacity
      of the MNCs to resorb was abolished by culturing the fibroblast-PBMC cultures
      with M-CSF and RANKL. Our results suggest that tooth-associated fibroblasts may
      trigger the formation of osteoclast-like cells, but more importantly, they play a
      role in preventing bone resorption, since additional stimuli are required for the
      formation of active osteoclasts.

PMID- 16440317
TI  - Engineered nanoparticles as precise drug delivery systems.
AB  - With the remarkable development of nanotechnology in recent years, new drug
      delivery approaches based on the state-of-the-art nanotechnology have been
      receiving significant attention. Nanoparticles, an evolvement of nanotechnology,
      are increasingly considered as a potential candidate to carry therapeutic agents
      safely into a targeted compartment in an organ, particular tissue or cell. These
      particles are colloidal structures with a diameter smaller than 1,000 nm, and
      therefore can penetrate through diminutive capillaries into the cell's internal
      machinery. This innovative delivery technique might be a promising technology to
      meet the current challenges in drug delivery. When loaded with a gene or drug
      agent, nanoparticles can become nanopills, which can effectively treat
      problematical diseases such as cancer. This article summarizes different types of
      nanoparticles drug delivery systems under investigation and their prospective
      therapeutic applications. Also, this article presents a closer look at the
      advances, current challenges, and future direction of nanoparticles drug delivery
      systems.

PMID- 16440318
TI  - Defining the transcriptome of accelerated and replicatively senescent
      keratinocytes reveals links to differentiation, interferon signaling, and Notch
      related pathways.
AB  - Epidermal keratinocytes (KCs) undergo highly orchestrated morphological and
      molecular changes during transition from proliferative compartment into growth
      arrested early and late differentiation layers, prior to dying in outermost
      cornified layers of normal skin. Creation of stratum corneum is vital to barrier
      function protecting against infection. Transcriptional events in KCs regulating
      complex processes of differentiation and host defense required to maintain
      constant epidermal thickness and resistance to infection in either young or aged
      skin are largely unknown. Furthermore, as terminal differentiation is
      characterized by irreversible loss of replicative potential culminating in dead
      layers at the skin surface, this process may be viewed as a form of senescence.
      However, a complete transcriptional profile of senescent (SN) human KCs has not
      been previously defined to permit delineation of molecular boundaries involving
      differentiation and senescence. To fill this void, we utilized global
      transcriptional analysis of KCs maintained in vitro as either cultures of
      proliferating (PR) cells, early and late confluent (LC) (accelerated senescence)
      cultures, or KCs undergoing replicative senescence. Global gene expression
      profiling revealed early confluent (EC) KCs were somewhat similar to PR KCs,
      while prominent differences were evident when compared to LC KCs; which were also
      distinct from replicatively SN KCs. While confluent KCs have in common several
      genes regulating differentiation with replicatively SN KCs, the latter cells
      expressed elevated levels of genes involved in interferon signaling and
      inflammatory pathways. These results provide new insights into cell autonomous
      transcriptional-based programs operative within KCs contributing to replicative
      senescence, with partial sharing of genes involved in differentiation. In
      addition, regulation of KC senescence may involve participation of interferon
      signaling pathways derived from the important role of KCs in protecting skin from
      infection. Integrating all of the transcriptional data revealed a key role for
      Notch receptor mediated signaling in the confluency induced differentiation
      phenotype using this model system.

PMID- 16440319
TI  - Probing membrane proteins using atomic force microscopy.
AB  - To gain insights into how biological molecules function, advanced technologies
      enabling imaging, sensing, and actuating single molecules are required. The
      atomic force microscope (AFM) would be one of novel potential tools for these
      tasks. In this study, techniques and efforts using AFM to probe biomolecules are
      introduced and reviewed. The state-of-art techniques for characterizing specific
      single receptor using the functionalized AFM tip are discussed. An example of
      studying the angiotensin II type 1 (AT1) receptors expressed in sensory neuronal
      cells by AFM with a functionalized tip is given. Perspectives for identifying and
      characterizing specific individual membrane proteins using AFM in living cells
      are provided. Given that many diseases have their roots at the molecular scale
      and are best understood as a malfunctioning biological nanomachines, the
      prospects of these unique techniques in basic biomedical research or in clinical
      practice are beyond our imagination.

PMID- 16440320
TI  - Transcriptional co-repressors of Runx2.
AB  - Runx2 is an essential transcription factor for skeletal mineralization because it
      stimulates osteoblast differentiation of mesenchymal stem cells, promotes
      chondrocyte hypertrophy, and contributes to endothelial cell migration and
      vascular invasion of developing bones. Runx2 is also expressed during mouse
      embryo development in nascent mammary gland epithelium. Recent evidence
      implicates deregulation of Runx2 as a contributing factor in breast cancer
      induced osteolysis and invasion, as well as in ectopic vascular calcification.
      Like other Runt domain proteins, Runx2 is a context-dependent transcriptional
      activator and repressor of genes that regulate cellular proliferation and
      differentiation. Proteins that temporally and spatially associate with Runx2
      dictate these opposing transcriptional activities. Recent studies have identified
      several co-repressor proteins that bind to Runx2 to regulate gene expression.
      These co-factors include histone deacetylases (HDACs), transducin-like enhancer
      of split (TLE) proteins, mSin3a, and yes-associated protein (YAP). These proteins
      do not bind DNA themselves and appear to act by preventing Runx2 from binding
      DNA, altering chromatin structure, and/or by possibly blocking co-activator
      complexes. The nuclear localization of several of these factors is regulated by
      extracellular signaling events. Understanding the mechanisms whereby co-repressor
      proteins affect Runx2 activity during normal cellular development and tumor
      progression will identify new therapeutic targets for skeletal disorders such as
      osteoporosis and for bone metastatic cancers.

PMID- 16440321
TI  - Knockdown of hypoxia-inducible factor-1alpha by siRNA inhibits C2C12 myoblast
      differentiation.
AB  - We analyzed the role of Hypoxia-inducible factor (HIF)-1alpha in myoblast
      differentiation by examining the expression and regulation of HIF-1alpha in
      proliferating and differentiating C2C12 myoblast, and by knocking down HIF-1alpha
      of C2C12 myoblasts with small interfering RNA (siRNA), given that HIF-1alpha has
      been shown to be involved in differentiative process in non-muscle tissues.
      Although HIF-1alpha mRNA was constantly expressed in C2C12 myoblasts both under
      growth and differentiating phase, HIF-1alpha protein was hardly detectable in the
      growth phase but became detectable only during myogenic differentiation even
      under normoxia. During early stage of C2C12 myogenesis, HIF-1alpha accumulated in
      the nuclei of myogenin-positive myoblasts. The inhibition of proteasome in the
      growth phase led to HIF-1alpha protein accumulation, whereas in the
      differentiation phase the inhibition of Hsp90, which stabilizes HIF-1alpha,
      suppressed HIF-1alpha accumulation. Therefore, we suggest that the level of HIF
      1alpha protein expression is regulated by a proteasome-and chaperon-dependent
      pathway in C2C12 myoblast. Knockdown of HIF-1alpha effectively blocked myotube
      formation and myosin heavy chain (MHC) expression. Finally, HIF-1alpha expression
      in vivo was confirmed in the regenerative muscle tissue of mice after eccentric
      exercise. We conclude that HIF-1alpha is required for C2C12 myogenesis in vitro,
      and suggest that HIF-1alpha may have an essential role in regenerative muscle
      tissue in vivo.

PMID- 16440323
TI  - Hyperthermia engages the intrinsic apoptotic pathway by enhancing upstream
      caspase activation to overcome apoptotic resistance in MCF-7 breast
      adenocarcinoma cells.
AB  - Febrile hyperthermia enhanced TNF-stimulated apoptosis of MCF-7 cells and
      overcame resistance in a TNF-resistant, MCF-7 variant (3E9), increasing their TNF
      sensitivity by 10- and 100-fold, respectively. In either cell line, the
      hyperthermic potentiation was attributable to increased apoptosis that was
      totally quenched by caspase inhibition. In MCF-7 cells, hyperthermic potentiation
      of apoptosis was associated with sustained activation of upstream caspases in
      response to TNF and more prominent engagement of the intrinsic apoptotic pathway.
      Apoptotic enhancement by hyperthermia was primarily mediated by caspase-8
      activation, as the specific inhibitor, Z-IETD, blocked cell death, whereas direct
      engagement of the intrinsic apoptotic pathway (with doxorubicin) was not
      affected. In 3E9 cells, hyperthermia alone induced activation of caspase-8, and
      was further enhanced by TNF. In 3E9 cells, hyperthermia caused TNF-dependent loss
      of mitochondrial membrane potential and activation of capspase-9 that was
      initiated and dependent on upstream caspases. MCF-7 and 3E9 cells were equally
      sensitive to exogenous C(6)-ceramide, but mass spectroscopic analysis of ceramide
      species indicated that total ceramide content was not enhanced by TNF and/or
      hyperthermia treatment, and that the combination of TNF and hyperthermia caused
      only modest elevation of one species (dihydro-palmitoyl ceramide). We conclude
      that febrile hyperthermia potentiates apoptosis of MCF-7 cells and overcomes TNF
      resistance by sustained activation of caspase-8 and engagement of the intrinsic
      pathway that is independent of ceramide flux. This report provides the first
      evidence for regulation of caspase-dependent apoptosis by febrile hyperthermia.

PMID- 16440322
TI  - CCN2, connective tissue growth factor, stimulates collagen deposition by gingival
      fibroblasts via module 3 and alpha6- and beta1 integrins.
AB  - CCN2, (connective tissue growth factor, CTGF) is a matricellular factor
      associated with fibrosis that plays an important role in the production and
      maintenance of fibrotic lesions. Increased collagen deposition and accumulation
      is a common feature of fibrotic tissues. The mechanisms by which CCN2/CTGF
      contributes to fibrosis are not well understood. Previous studies suggest that
      CTGF exerts some of its biological effects at least in part by integrin binding,
      though this mechanism has not been previously shown to contribute to fibrosis.
      Utilizing full length CCN2/CTGF, CCN2/CTGF fragments, and integrin neutralizing
      antibodies, we provide evidence that the effects of CCN2/CTGF to stimulate
      extracellular matrix deposition by gingival fibroblasts are mediated by the C
      terminal half of CCN2/CTGF, and by alpha6 and beta1 integrins. In addition, a
      synthetic peptide corresponding to a region of CCN2/CTGF domain 3 that binds
      alpha6beta1 inhibits the collagen-deposition assay. These studies employed a new
      and relatively rapid assay for CCN2/CTGF-stimulated collagen deposition based on
      Sirius Red staining of cell layers. Data obtained support a pathway in which
      CCN2/CTGF could bind to alpha6beta1 integrin and stimulate collagen deposition.
      These findings provide new experimental methodologies applicable to uncovering
      the mechanism and signal transduction pathways of CCN2/CTGF-mediated collagen
      deposition, and may provide insights into potential therapeutic strategies to
      treat gingival fibrosis and other fibrotic conditions.

PMID- 16440324
TI  - Role of osteoblast suppression in multiple myeloma.
AB  - Multiple myeloma is the most common form of plasma cell dyscrasia and virtually
      all cases of myeloma exhibit osteolytic lesions, which result in bone pain,
      pathological fractures, spinal cord compression, and hypercalcaemia. Malignant
      plasma cells disrupt the delicate balance between bone formation and bone
      resorption, which ultimately leads to the debilitating osteolytic lesions. This
      review focuses principally on mechanisms of osteoblast inhibition by malignant
      plasma cells with emphasis placed on our experimental findings, which support a
      model for abnormal Wnt signaling in osteoblast suppression. We describe how
      excessive amounts of soluble Wnt inhibitors secreted by malignant plasma cells in
      multiple myeloma could promote osteolytic lesions, tumor growth, suppress
      hematopoiesis, prevent proper engraftment, and expansion of transplanted stem
      cells. Finally, we detail current therapies shown to disrupt the interaction
      between the myeloma cell and the microenvironment, leading to activation of
      osteoblasts.

PMID- 16440325
TI  - RNAi-mediated silencing of insulin receptor substrate 1 (IRS-1) enhances
      tamoxifen-induced cell death in MCF-7 breast cancer cells.
AB  - Insulin receptor substrate 1 (IRS-1) is a major downstream signaling protein for
      insulin and insulin-like growth factor I (IGF-I) receptors, conveying signals to
      PI-3K/Akt and ERK1/2 pathways. In breast cancer, IRS-1 overexpression has been
      associated with tumor development, hormone-independence and antiestrogen
      resistance. In part, these effects are related to potentiation of IRS-1/PI-3K/Akt
      signaling. In estrogen sensitive breast cancer cell lines, tamoxifen treatment
      reduces IRS-1 expression and function; consequently, inhibiting IRS-1/PI-3K
      signaling. We tested whether anti-IRS1 siRNA could inhibit growth and survival of
      estrogen-sensitive MCF-7 breast cancer cells, when used alone or in combination
      with TAM. Our results indicated: (a) out of four tested anti-IRS1 siRNAs, two
      siRNAs reduced IRS-1 protein by approximately three-fold in both growing and IGF
      I-stimulated cells without affecting a closely related protein, IRS-2; (b) these
      effects paralleled IRS1 mRNA downregulation by approximately three-fold, measured
      by quantitative real time-polymerase chain reaction; (c) action of anti-IRS1
      siRNAs induced the apoptotic response, observed by altered mitochondrial membrane
      potential coupled with downregulation of NF-kappaB target Bcl-xL and reduced cell
      viability; (d) anti-IRS1 siRNA treatment enhanced the cytotoxic effects of TAM by
      approximately 20%. In summary, anti-IRS1 RNAi strategy could become a potent tool
      to induce breast cancer cell death, especially if combined with standard TAM
      therapy.

PMID- 16440326
TI  - Salvianolic acid B attenuates cyclooxygenase-2 expression in vitro in LPS-treated
      human aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient
      mouse aorta.
AB  - Inflammation plays an essential role in atherosclerosis and post-angioplasty
      restenosis and the synthesis and release of inflammatory cytokines from vascular
      smooth muscle cells is an important contributor to these pathologies. It is
      assumed that drugs that prevent the overproduction of inflammatory cytokines may
      inhibit cardiovascular disorders. In the present study, the effects of a water
      soluble antioxidant, salvianolic acid B (Sal B), derived from a Chinese herb, on
      the expression of cyclooxygenase (COX) in lipopolysaccharide (LPS)-treated human
      aortic smooth muscle cells (HASMCs) and in the aortas of cholesterol-fed apoE
      deficient mice were investigated. In unstimulated HASMCs, COX-2 mRNA and protein
      were almost undetectable, but were strongly upregulated in response to LPS. In
      contrast, HASMCs with or without LPS treatment showed constitutive expression of
      COX-1 mRNA and protein. The activation of COX-2 protein synthesis in LPS
      stimulated HASMCs was shown to involve the activation of the extracellular-signal
      regulated kinase 1/2 (ERK1/2), c-Jun NH(2)-terminal kinase (JNK), and p38 mitogen
      activated protein kinase pathway. Incubation of HASMCs with Sal B before LPS
      stimulation resulted in pronounced downregulation of COX-2 expression. Sal B
      treatment suppressed ERK1/2 and JNK phosphorylation and attenuated the increase
      in prostaglandin E(2) production and NADPH oxidase activity in LPS-treated
      HASMCs. When apoE-deficient mice were fed a 0.15% cholesterol diet with or
      without supplementation with 0.3% Sal B for 12 weeks, the intima/media area ratio
      in the thoracic aortas was significantly reduced in the Sal B group (0.010 +/-
      0.009%) compared to the apoE-deficient group (0.114 +/- 0.043%) and there was a
      significant reduction in COX-2 protein expression in the thickened intima. These
      results demonstrate that Sal B has anti-inflammatory properties and may explain
      its anti-atherosclerotic properties. This new mechanism of action of Sal B, in
      addition to its previously reported inhibition of LDL oxidation, may help explain
      its efficacy in the treatment of atherosclerosis.

PMID- 16440327
TI  - 1Alpha,25-dihydroxyvitamin D3-mediated stimulation of steroid sulphatase activity
      in myeloid leukaemic cell lines requires VDRnuc-mediated activation of the
      RAS/RAF/ERK-MAP kinase signalling pathway.
AB  - 1Alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) stimulates the activity of
      steroid sulphatase (STS) in myeloid cells [Hughes et al., 2001, 2005]. This was
      attenuated by inhibitors of phospholipase D (PLD) (n-butanol, 2,3
      diphosphoglyceric acid, C(2)-ceramide) and phosphatidate phosphohydrolase (PAP)
      (propranolol and chlorpromazine), but was unaffected by inhibitors of
      phospholipase C. The 1alpha,25(OH)(2)D(3)-induced STS activity was also
      attenuated by inhibitors of protein kinase Calpha and protein kinase Cdelta (Go
      6976, HBDDE and rottlerin), but not by an inhibitor of protein kinase Cbeta
      (LY379196). Additionally, 1alpha,25(OH)(2)D(3)-induced STS activity was
      attenuated by inhibitors of RAS (manumycin A), RAF (GW5074), MEK (PD098059 and
      U1026) and JNK (SP600125), but not p38 (PD169316). 1alpha,25(OH)(2)D(3) produced
      a rapid and long lasting stimulation of the ERK-MAP kinase signalling cascade in
      HL60 myeloid leukaemic cells. This 'non-genomic' effect of 1alpha,25(OH)(2)D(3)
      blocked by pharmacological antagonists of nuclear vitamin D receptors (VDR(nuc))
      and does not appear to require hetero-dimerisation with the retinoid-X receptor
      (RXR). Inhibitors of the Src tyrosine kinase (PP1), RAS (manumycin A), RAS-RAF
      interactions (sulindac sulphide and RAS inhibitory peptide), RAF (GW5074 or
      chloroquine), and protein kinase Calpha (HBDDE) abrogated the
      1alpha,25(OH)(2)D(3)-stimulated increase in ERK-MAP kinase activity. Taken
      together, these results show that 1alpha,25(OH)(2)D(3)/VDR(nuc) activation of the
      RAS/RAF/ERK-MAP kinase signalling pathway plays an important role in augmenting
      STS activity in human myeloid leukaemic cell lines.

PMID- 16440328
TI  - DNA vaccines: successes and limitations in cancer and infectious disease.
AB  - Vaccination with plasmid DNA is an active area of investigation that is being
      applied to diseases including cancer and microbial pathogens associated with
      infectious diseases. Since its discovery, great progress has been made with the
      administration of DNA vaccines to initiate specific and effective immune
      responses against targeted illnesses. However, many obstacles still face its use
      in prophylactic and therapeutic vaccination scenarios. The nature of these
      difficulties alongside the successes and future of plasmid DNA will be discussed.

PMID- 16440329
TI  - Lysyl oxidase regulates actin filament formation through the
      p130(Cas)/Crk/DOCK180 signaling complex.
AB  - We have previously demonstrated that lysyl oxidase (LOX) is expressed in invasive
      breast cancer cells compared to poorly invasive cells. Additionally, we have
      recently shown that LOX regulates cell migration, a key step in the invasion
      process, through a hydrogen peroxide-dependent mechanism involving the focal
      adhesion kinase (FAK)/Src signaling complex. Here we further elucidate the role
      of LOX in cell motility/migration by examining the role of LOX in actin filament
      polymerization. We demonstrate that inhibition of LOX leads to an increase in
      phalloidin staining, directly associated with an increase in actin stress fiber
      formation. This increase in staining was confirmed by activity assays showing an
      increase in Rho activity with decreased LOX activity. Additionally, Rac and Cdc42
      activity decreased with the reduction in LOX activity. Taken together, these data
      demonstrate a loss of a motogenic phenotype with decreased LOX activity. Finally,
      in order to elucidate the mechanism by which LOX regulates actin polymerization,
      we have demonstrated that LOX facilitates p130(Cas) phosphorylation, which allows
      for the binding to CAS related kinase (Crk) and formation of the
      p130(Cas)/Crk/DOCK180 signaling complex. Formation of this complex leads to an
      increase in Rac-GTP, which decreases actin stress fiber formation and increases
      formation of lamellipodium. These data demonstrate that LOX regulates cell
      motility/migration through changes in actin filament polymerization, which
      involve the regulation of the p130(Cas)/Crk/DOCK180 signaling pathway.
      Elucidating the role of LOX in the regulation of cell motility will allow the
      development of more effective therapeutic strategies to treat invasive/metastatic
      breast cancer.

PMID- 16440330
TI  - Dual involvement of protein kinase C delta in apoptosis induced by syndecan-2 in
      osteoblasts.
AB  - Syndecans are proteoglycans that act as signaling molecules. Previously, we
      showed that syndecan-2 (SYND2) is involved in the control of osteoblastic (OB)
      cell apoptosis. Here, we show a novel functional interaction between SYND2 and
      protein kinase C delta (PKCdelta). Overexpression of SYND2 in MG63 OB cells
      resulted in increased PKCdelta protein level without change in PKCdelta mRNA
      production. In SYND2-transfected cells, the increase in PKCdelta was restricted
      to the cytosolic compartment, threonine 505-PKCdelta was underphosphorylated and
      immunoprecipitated PKCdelta showed decreased capacity to phosphorylate histone,
      indicating that SYND2 decreased PKCdelta activity. Inhibition of PKCdelta by
      Rottlerin or a dead-kinase dominant negative (DN) construct activated effector
      caspases and increased the number of apoptotic cells. In addition, rescue of
      kinase activity with a construct coding, the PKCdelta catalytic domain (CAT)
      reduced SYND2-induced apoptosis. This indicates that PKCdelta acts as a pro
      survival kinase and that SYND2 inhibits the anti-apoptotic action of PKCdelta in
      OB cells. We also showed that overexpression of PKCdelta wild type (WT) induced
      osteoblast apoptosis. Moreover, inhibition of PKCdelta by siRNA resulted in
      increased apoptosis in control cells but reduced apoptosis in SYND2
      overexpressing osteoblasts, indicating that SYND2 requires PKCdelta accumulation
      to induce apoptosis. These results show that SYND2 modulates PKCdelta actions by
      inhibition of the canonical allosterical activation pathway that plays an anti
      apoptotic role in OB cells, and promotion of a pro-apoptotic role that may depend
      on PKCdelta protein level and that participates to the induction of cell death by
      SYND2. This establishes a functional interaction between SYND2 and PKCdelta in
      osteoblasts.

PMID- 16440332
TI  - Botulinum toxin type A for drooling in Parkinson's disease: a double-blind,
      randomized, placebo-controlled study.
AB  - To investigate the safety and efficacy of botulinum toxin type A (BoNTX)
      treatment to reduce sialorrhea in Parkinson's disease (PD), a double-blind,
      randomized, placebo-controlled study enrolled 32 PD patients complaining of
      excessive drooling. Patients received either 50 U Botox in each parotid gland or
      placebo without using ultrasound guidance. Subjects treated with BoNTX
      experienced a reduction in both drooling frequency and familial and social
      disability (TimexGroup effect: P<0.01), as well as in saliva production (Time x
      Group effect: P<0.0001). No adverse events were recorded. BoNTX injections are
      safe and effective treatment for the management of PD-related drooling.

PMID- 16440331
TI  - Quantifying effects of ligands on androgen receptor nuclear translocation,
      intranuclear dynamics, and solubility.
AB  - Using manual and automated high throughput microscopy (HTM), ligand-dependent
      trafficking of green fluorescent protein-androgen receptor (GFP-AR) was analyzed
      in fixed and living cells to determine its spatial distribution, solubility,
      mobility, and co-activator interactions. Within minutes, addition of the agonist
      R1881 resulted translocation of GFP-AR from the cytoplasm to the nucleus, where
      it displayed a hyperspeckled pattern and extraction resistance in low expressing
      cells. AR antagonists (Casodex, hydroxyflutamide) also caused nuclear
      translocation, however, the antagonist-bound GFP-AR had a more diffuse nuclear
      distribution, distinct from the agonist-bound GFP-AR, and was completely soluble;
      overexpressed GFP-AR in treated cells was extraction resistant, independent of
      ligand type. To more dramatically show the different effects of ligand on AR
      distribution, we utilized an AR with a mutation in the DNA binding domain
      (ARC619Y) that forms distinct foci upon exposure to agonists but retains a
      diffuse nuclear distribution in the presence of antagonists. Live-cell imaging of
      this mutant demonstrated that cytoplasmic foci formation occurs immediately upon
      agonist but not antagonist addition. Fluorescence recovery after photobleaching
      (FRAP) revealed that agonist-bound GFP-AR exhibited reduced mobility relative to
      unliganded or antagonist-bound GFP-AR. Importantly, agonist-bound GFP-AR mobility
      was strongly affected by protein expression levels in transiently transfected
      cells, and displayed reduced mobility even in slightly overexpressing cells. Cyan
      fluorescent protein-AR (CFP-AR) and yellow fluorescent protein-CREB binding
      protein (YFP-CBP) in the presence of agonists and antagonists were used to
      demonstrate that CFP-AR specifically co-localizes with YFP-CBP in an agonist
      dependent manner. Dual FRAP experiments demonstrated that CBP mobility mirrored
      AR mobility only in the presence of agonist. HTM enabled simultaneous studies of
      the sub-cellular distribution of GFP-AR and ARC619Y in response to a range of
      concentrations of agonists and antagonists (ranging from 10(-12) to 10(-5)) in
      thousands of cells. These results further support the notion that ligand specific
      interactions rapidly affect receptor and co-factor organization, solubility, and
      molecular dynamics, and each can be aberrantly affected by mutation and
      overexpression.

PMID- 16440333
TI  - Improvement in a quantitative measure of bradykinesia after microelectrode
      recording in patients with Parkinson's disease during deep brain stimulation
      surgery.
AB  - It is widely accepted that patients with Parkinson's disease experience immediate
      but temporary improvement in motor signs after surgical implantation of
      subthalamic nucleus (STN) deep brain stimulating electrodes before the electrodes
      are activated, although this has never been formally studied. Based on anecdotal
      observations that limb mobility improved just after microelectrode recording
      (MER) during deep brain stimulation (DBS) procedures, we designed a prospective
      study to measure upper extremity bradykinesia using a quantitative measure of
      angular velocity. Measurements were made pre- and post-MER and during
      intraoperative DBS. Analysis of 98 STN DBS procedures performed on 61 patients
      showed that MER did not create adverse clinical symptoms despite concerns that
      MER increases morbidity. Quantitative upper extremity bradykinesia improved after
      MER alone, and further improvement was seen during intraoperative DBS.
      Electrophysiological data from each case were then compared to the improvement in
      bradykinesia post-MER alone and a significant correlation was found between the
      improvement in arm bradykinesia, the number of passes through the STN with
      somatosensory driving, and also with the number of arm cells with somatosensory
      driving in the STN, but not with total number of passes, total number of passes
      through the STN, or total number of cells with somatosensory driving in the STN.
      This study demonstrates that there is a significant improvement in upper
      extremity bradykinesia just after MER, before inserting or activating the DBS
      electrode in patients with Parkinson's disease who undergo STN DBS.

PMID- 16440334
TI  - Activin A induces erythroid gene expressions and inhibits mitogenic cytokine
      mediated K562 colony formation by activating p38 MAPK.
AB  - Activin A, a member of the transforming growth factor (TGF)-beta superfamily, is
      involved in the regulation of erythroid differentiation. Previous studies have
      shown that activin A inhibited the colony-forming activity of mouse Friend
      erythroleukemia cells, however, the mechanism remains unknown. First, we show
      herein that activin A induced the expression and activated the promoters of alpha
      globin and zeta-globin in K562 cells, confirming that activin A induces erythroid
      differentiation in K562 cells. The p38 mitogen activated protein kinase (MAPK)
      inhibitor, SB203580, inhibited and the extracellular signal regulated kinase
      (ERK) inhibitor, PD98059, enhanced the expression and promoter activities of
      alpha-globin and zeta-globin by activin A, indicating that p38 MAPK and ERK are
      crucial for activin A-induced erythroid genes expression. Second, SB203580
      inhibited the inhibitory effect of activin A on the colony-forming activity of
      K562 cells using the methylcellulose colony assay, indicating that activin A
      inhibits K562 colony formation by activating p38 MAPK. In addition, mitogenic
      cytokines SCF, IL-3, and GM-CSF induced colony formation of K562 cells that could
      be inhibited by PD98059 or enhanced by SB203580, respectively, indicating that
      these mitogenic cytokines induce K562 colony formation by activating ERK and
      inactivating p38 MAPK. Furthermore, activin A reduced the induction effect of
      these mitogenic cytokines on K562 colony formation in a dose-dependent manner.
      The inhibition of p38 MAPK reverted the inhibitory effect of activin A on
      mitogenic cytokine-mediated K562 colony formation. We conclude that activin A can
      regulate the same pathway via p38 MAPK to coordinate cell proliferation and
      differentiation of K562 cells.

PMID- 16440337
TI  - Liver endothelial cells promote LDL-R expression and the uptake of HCV-like
      particles in primary rat and human hepatocytes.
AB  - Low-density lipoprotein (LDL) is an important carrier of plasma cholesterol and
      triglycerides whose concentration is regulated by the liver parenchymal cells.
      Abnormal LDL regulation is thought to cause atherosclerosis, while viral binding
      to LDL has been suggested to facilitate hepatitis C infection. Primary
      hepatocytes quickly lose the ability to clear LDL during in vitro culture. Here
      we show that the coculture of hepatocytes with liver sinusoidal endothelial cells
      (LSEC) significantly increases the ability of hepatocytes to uptake LDL in vitro.
      LDL uptake does not increase when hepatocytes are cocultured with other cell
      types such as fibroblasts or umbilical vein endothelial cells. We find that LSECs
      induce the hepatic expression of the LDL receptor and the epidermal growth factor
      receptor. In addition, while hepatocytes in single culture did not take up
      hepatitis C virus (HCV)-like particles, the hepatocytes cocultured with LSECs
      showed a high level of HCV-like particle uptake. We suggest that coculture with
      LSECs induces the emergence of a sinusoidal surface in primary hepatocytes
      conducive to the uptake of HCV-like particles. In conclusion, our findings
      describe a novel model of polarized hepatocytes in vitro that can be used for the
      study of LDL metabolism and hepatitis C infection.

PMID- 16440338
TI  - Isolation and characterization of lipid microdomains from apical and basolateral
      plasma membranes of rat hepatocytes.
AB  - Canalicular bile is formed by the osmotic filtration of water in response to
      osmotic gradients generated by active transport at the apical and basolateral
      plasma membrane domains of hepatocytes. We recently demonstrated that mixed
      plasma membrane fractions isolated from rat hepatocyte couplets contain lipid
      microdomains ("rafts") enriched in cholesterol and sphingolipids and AQP8 and 9.
      We isolated lipid microdomains from hepatocyte apical and basolateral plasma
      membrane domains using Triton X-100 as detergent, and characterized their lipid
      and protein composition. A Triton-insoluble band ("raft fraction") at the 5%/30%
      sucrose interface in both apical and basolateral fractions was enriched for
      alkaline phosphatase (apical) and Na/K ATPase (basolateral) and was negative for
      amino peptidase-N. This detergent-insoluble band was also positive for caveolin-1
      (a "raft" associated protein) and negative for clathrin (a "raft" negative
      protein). Lipid analysis showed that, the Triton-insoluble fraction was highly
      enriched in cholesterol and sphingolipids. Immunofluorescence staining on
      hepatocyte couplets for both caveolin-1 and cholera toxin B showed a punctate
      distribution on both the apical and basolateral plasma membranes, consistent with
      localized membrane microdomains. Dot blot analysis showed that the "raft"
      associated ganglioside GM1 was enriched in the detergent-insoluble fraction both
      domains. Furthermore, exposure of isolated hepatocytes to glucagon, a choleretic
      agonist, significantly increased the expression of AQP8 associated with the
      apical microdomain fractions but had no effect on AQP9 expression in the
      basolateral microdomain fractions. In conclusion, "rafts" represent target
      microdomains for exocytic insertion and retrieval of "flux proteins", including
      AQPs, involved in canalicular bile secretion.

PMID- 16440339
TI  - Deoxyribonuclease 1 aggravates acetaminophen-induced liver necrosis in male CD-1
      mice.
AB  - An overdose of acetaminophen (APAP) (N-acetyl-p-aminophenol) leads to
      hepatocellular necrosis induced by its metabolite N-acetyl-p-benzoquinone-imine,
      which is generated during the metabolic phase of liver intoxication. It has been
      reported that DNA damage occurs during the toxic phase; however, the nucleases
      responsible for this effect are unknown. In this study, we analyzed the
      participation of the hepatic endonuclease deoxyribonuclease 1 (DNASE1) during
      APAP-induced hepatotoxicity by employing a Dnase1 knockout (KO) mouse model. Male
      CD-1 Dnase1 wild-type (WT) (Dnase1+/+) and KO (Dnase1-/-) mice were treated with
      2 different doses of APAP. Hepatic histopathology was performed, and biochemical
      parameters for APAP metabolism and necrosis were investigated, including
      depletion of glutathione/glutathione-disulfide (GSH+GSSG), beta-nicotinamide
      adenine dinucleotide (NADH+NAD+), and adenosine triphosphate (ATP); release of
      aminotransferases and Dnase1; and occurrence of DNA fragmentation. As expected,
      an APAP overdose in WT mice led to massive hepatocellular necrosis characterized
      by the release of aminotransferases and depletion of hepatocellular GSH+GSSG,
      NADH+NAD+, and ATP. These metabolic events were accompanied by extensive DNA
      degradation. In contrast, Dnase1 KO mice were considerably less affected. In
      conclusion, whereas the innermost pericentral hepatocytes of both mouse strains
      underwent necrosis to the same extent independent of DNA damage, the progression
      of necrosis to more outwardly located cells was dependent on DNA damage and only
      occurred in WT mice. Dnase1 aggravates APAP-induced liver necrosis.

PMID- 16440340
TI  - Reassessment of the algorithm for prediction of liver fibrosis in patients with
      features of the metabolic syndrome.

PMID- 16440341
TI  - Recovery of scrap iron metal value using biogenerated ferric iron.
AB  - The utility of employing biogenerated ferric iron as an oxidant for the recycling
      of scrap metal has been demonstrated using continuously growing cells of the
      extremophilic organism Acidithiobacillus ferrooxidans. A ferric iron rich (70
      mol%) lixiviant resulting from bioreactor based growth of A. ferrooxidans readily
      solubilized target scrap metal with the resultant generation of a leachate
      containing elevated ferrous iron levels and solubilized copper previously
      resident in the scrap metal. Recovery of the copper value was easily accomplished
      via a cementation reaction and the clarified leachate containing a replenished
      level of ferrous iron as growth substrate was shown to support the growth of A.
      ferrooxidans and be fully recyclable. The described process for scrap metal
      recycling and copper recovery was shown to be efficient and economically
      attractive. Additionally, the utility of employing the E(h) of the growth medium
      as a means for monitoring fluctuations in cell density in cultures of A.
      ferrooxidans is demonstrated.

PMID- 16440342
TI  - CD4+ T cells contribute to postischemic liver injury in mice by interacting with
      sinusoidal endothelium and platelets.
AB  - The mechanisms by which T cells contribute to the hepatic inflammation during
      antigen-independent ischemia/reperfusion (I/R) are not fully understood. We
      analyzed the recruitment of T cells in the postischemic hepatic microcirculation
      in vivo and tested the hypothesis that T cells interact with platelets and
      activate sinusoidal endothelial cells, resulting in microvascular dysfunction
      followed by tissue injury. Using intravital videofluorescence microscopy, we show
      in mice that warm hepatic I/R (90/30-140 min) induces accumulation and
      transendothelial migration of CD4+, but not CD8+ T cells in sinusoids during
      early reperfusion. Simultaneous visualization of fluorescence-labeled CD4+ T
      cells and platelets showed that approximately 30% of all accumulated CD4+ T cells
      were colocalized with platelets, suggesting an interaction between both cell
      types. Although interactions of CD4+/CD40L-/- T cells with CD40L-/- platelets in
      wild-type mice were slightly reduced, they were almost absent if CD4+ T cells and
      platelets were from CD62P-/- mice. CD4 deficiency as well as CD40-CD40L and CD28
      B7 disruption attenuated postischemic platelet adherence in the same manner as
      platelet inactivation with a glycoprotein IIb/IIIa antagonist and reduced
      neutrophil transmigration, sinusoidal perfusion failure, and transaminase
      activities. Treatment with an MHC class II antibody, however, did not affect I/R
      injury. In conclusion, we describe the type, kinetic, and microvascular
      localization of T cell recruitment in the postischemic liver. CD4+ T cells
      interact with platelets in postischemic sinusoids, and this interaction is
      mediated by platelet CD62P. CD4+ T cells activate endothelium, increase I/R
      induced platelet adherence and neutrophil migration via CD40-CD40L and CD28-B7
      dependent pathways, and aggravate microvascular/hepatocellular injury.

PMID- 16440344
TI  - Noninvasive diagnosis of cirrhosis in chronic hepatitis C based on standard
      laboratory tests.

PMID- 16440343
TI  - The sources of parenchymal regeneration after chronic hepatocellular liver injury
      in mice.
AB  - After liver injury, parenchymal regeneration occurs through hepatocyte
      replication. However, during regenerative stress, oval cells (OCs) and small
      hepatocyte like progenitor cells (SHPCs) contribute to the process. We
      systematically studied the intra-hepatic and extra-hepatic sources of liver cell
      replacement in the hepatitis B surface antigen (HBsAg-tg) mouse model of chronic
      liver injury. Female HBsAg-tg mice received a bone marrow (BM) transplant from
      male HBsAg-negative mice, and half of these animals received retrorsine to block
      indigenous hepatocyte proliferation. Livers were examined 3 and 6 months post-BM
      transplantation for evidence of BM-derived hepatocytes, OCs, and SHPCs. In
      animals that did not receive retrorsine, parenchymal regeneration occurred
      through hepatocyte replication, and the BM very rarely contributed to hepatocyte
      regeneration. In mice receiving retrorsine, 4.8% of hepatocytes were Y chromosome
      positive at 3 months, but this was frequently attributable to cell fusion between
      indigenous hepatocytes and donor BM, and their frequency decreased to 1.6% by 6
      months, as florid OC reactions and nodules of SHPCs developed. By analyzing
      serial sections and reconstructing a 3-dimensional map, continuous streams of OCs
      could be seen that surrounded and entered deep into the nodules of SHPCs,
      connecting directly with SHPCs, suggesting a conversion of OCs into SHPCs. In
      conclusion, during regenerative stress, the contribution to parenchymal
      regeneration from the BM is minor and frequently attributable to cell fusion. OCs
      and SHPCs are of intrinsic hepatic origin, and OCs can form SHPC nodules.

PMID- 16440345
TI  - Tightly regulated induction of the adhesion molecule necl-5/CD155 during rat
      liver regeneration and acute liver injury.
AB  - TuAg1/TagE4, the rat ortholog of the human poliovirus receptor CD155, is
      expressed on a high percentage of rat hepatocellular carcinomas. Recent studies
      have shown that TuAg1/TagE4/CD155 is a member of the nectin family of
      immunoglobulin (Ig)-like cell adhesion molecules, designated necl-5. Necl-5 is
      present at exceedingly low levels in adult epithelial tissues but is upregulated
      in primary cultures of rat hepatocytes, suggesting that disruption of liver
      architecture triggers its expression. To explore this possibility, we examined
      expression of necl-5 after two-thirds partial hepatectomy or carbon tetrachloride
      (CCl4)-induced acute injury. Using quantitative real-time polymerase chain
      reaction (QPCR), we found that necl-5 mRNA levels increased 15-fold by 9 hours,
      and decreased to 4-fold above baseline by 24 hours after partial hepatectomy.
      Necl-5 mRNA levels increased over 100-fold 6 hours after treatment with CCl4,
      reaching a peak of 140-fold above baseline by 10 hours, and thereafter rapidly
      declining. Necl-5 was localized at the membrane of midlobular and centrilobular
      hepatocytes 10 to 48 hours after CCl4 exposure. Northern blot analysis
      demonstrated a close correlation between the kinetics of necl-5 expression and
      the immediate-early response gene c-myc. Subconfluent cultures of the non
      transformed liver epithelial cell line WB-F344 expressed high levels of necl-5,
      which was down-regulated as cells approached confluence. The transformed WB-F344
      line GP7TB did not demonstrate density-dependent regulation of necl-5 expression.
      In conclusion, we report the in vivo induction of necl-5 in rat hepatocytes and
      provide evidence that both necl-5 mRNA and protein are tightly regulated in adult
      epithelial cells and tissue.

PMID- 16440346
TI  - Proteasome inhibition induces hepatic stellate cell apoptosis.
AB  - Induction of hepatic stellate cell (HSC) apoptosis attenuates hepatic fibrosis,
      and, therefore, mechanisms to induce HSC cell death are of therapeutic interest.
      Proteasome inhibitors induce apoptosis in transformed cells, especially those
      cells dependent upon nuclear factor kappa B (NF-kappaB) activation. Because
      stimulated HSCs also trigger NF-kappaB activation, the aim of this study was to
      determine if proteasome inhibitors induce HSC apoptosis. The immortalized human
      HSC line, LX-2, and primary rat HSCs were treated with the proteasome inhibitors
      bortezomib and MG132. Both proteasome inhibitors induced HSC apoptosis.
      Proteasome inhibition blocked NF-kappaB activation and, more importantly, NF
      kappaB inhibition by Bay11-7082-triggered HSC apoptosis. Activated HSC survival
      is dependent upon the NF-kappaB target gene A1, an anti-apoptotic Bcl-2 family
      member, as siRNA targeted knockdown of A1-induced HSC apoptosis. In contrast,
      proteasome inhibition-induced alterations in TRAIL, death receptor 5, and Bim
      could not be implicated in the apoptotic response. The relevance of these
      findings was confirmed in the bile-duct-ligated mouse where bortezomib reduced
      hepatic markers of stellate cell activation and fibrosis. In conclusion,
      proteasome inhibition is a potential therapeutic strategy for inducing HSC
      apoptosis and inhibiting liver fibrogenesis.

PMID- 16440347
TI  - Difference in cytotoxicity against hepatocellular carcinoma between liver and
      periphery natural killer cells in humans.
AB  - In rodents, liver natural killer (NK) cells have been shown to mediate higher
      cytotoxic activity against tumor cells than do peripheral blood (PB) NK cells.
      However, such differences between liver and PB NK cells have not been extensively
      investigated in humans. The phenotypical and functional properties of NK cells
      extracted from liver perfusates at the time of living donor liver transplantation
      were investigated. The tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL), a critical molecule for NK cell-mediated anti-tumor cell killing, was
      not expressed by freshly isolated PB NK cells or by liver NK cells. Stimulation
      with interleukin (IL)-2, significantly up-regulated the expression of TRAIL on
      liver NK cells, but this effect was barely observed on PB NK cells. Donor liver
      NK cells showed the most vigorous cytotoxicity against HepG2, a hepatocellular
      carcinoma (HCC) cell line, after IL-2 stimulation (90.5% +/- 2.2% at E: T =
      10:1), compared with donor and recipient PB NK cells and recipient liver NK cells
      (64.8% +/- 8.2%, 56.1% +/- 8.9%, and 34.6% +/- 7.5%, respectively). IL-2
      stimulation resulted in an increased expression of killing inhibitory receptors
      on liver NK cells in parallel with TRAIL expression. Consistently, the
      cytotoxicities of IL-2-stimulated donor liver NK cells against self and recipient
      lymphoblasts were negligible. In conclusion, adoptive transfer of IL-2-stimulated
      NK cells extracted from donor liver graft perfusate could mount an anti-tumor
      response without causing toxicity against 1-haplotype identical recipient intact
      tissues. These findings present a concept to prevent recurrence of HCC after
      liver transplantation.

PMID- 16440348
TI  - Seeded isothermal batch crystallization of lysozyme.
AB  - The kinetics of lysozyme crystallization under seeded isothermal batch conditions
      was followed by measurement of the decline in solution concentration versus time.
      Kinetics were measured for five different values of the seed crystal mass. The
      data were analyzed using a recently proposed mathematical model. For each seed
      mass, the model fit the kinetic data well. Growth rate constants determined using
      the model were approximately constant over a sixfold increase in the seed crystal
      mass, and fell well within the range of values reported in the literature, but
      obtained using entirely different experimental techniques. These results
      confirmed the utility of the proposed model. The proposed model can be used to
      analyze crystallization kinetics using absorbance measurements only, without the
      need to characterize the crystal size, thus avoiding the need for expensive laser
      light scattering and digital microscopy instrumentation. Thus, the model offers a
      low-cost straightforward method to analyze and simulate the effects of changes in
      operating parameters such as the seed crystal mass, solution volume, initial
      protein concentration, pH, temperature, salt concentration, and time.

PMID- 16440349
TI  - Gene expression and survival changes in Saccharomyces cerevisiae during
      suspension culture.
AB  - This study explores the connection between changes in gene expression and the
      genes that determine strain survival during suspension culture, using the model
      eukaryotic organism, Saccharomyces cerevisiae. The Saccharomyces cerevisiae
      homozygous diploid deletion pool (HDDP), and the BY4743 parental strain were
      grown for 18 h in a rotating wall vessel (RWV), a suspension culture device
      optimized to minimize the delivered shear. In addition to the reduced shear
      conditions, the RWVs were also placed in a static position or in a shaker in
      order to change the amount of shear stress on the cells. Using simple linear
      regression, it was found that there were 140 differentially expressed genes for
      which >70% of the variation can be explained by shear stress alone. A significant
      number of these genes are involved in catalytic activity. In the HDDP, shear
      stress was associated with significant survival changes in 15 deletion strains
      (R(2>) > 0.7) Interestingly, both analyses uncovered changes in the ribosomal
      protein machinery. Comparing the changes in gene expression and strain survival
      under the different shear conditions allows for the insights into the molecular
      mechanisms behind the cells response to shear stress. This in turn can provide
      information for the optimization of suspension culture.

PMID- 16440350
TI  - Use of glucose-responsive material to regulate insulin release from
      constitutively secreting cells.
AB  - Genetically-engineered cells offer a solution to the cell availability problem in
      tissue engineering a pancreatic substitute for the treatment of insulin-dependent
      diabetes. These cells can be non-beta cells, such as hepatocytes or myoblasts,
      retrieved as a biopsy from the same patient and genetically engineered to secrete
      recombinant insulin constitutively or under transcriptional regulation. However,
      the continuous or slowly responsive insulin secretion dynamics from these cells
      cannot provide physiologic glucose regulation in patients. Our objective consists
      of using such cells as an insulin source and of regulating insulin release by
      incorporating a glucose-responsive material, which acts as a control barrier for
      insulin in a cell-material hybrid device. Experiments were performed with
      insulinoma betaTC3 cells, HepG2 hepatomas, and C2C12 myoblasts, the latter two
      genetically-modified to constitutively secrete insulin. The control barrier
      consisted of concanavalin A (con A)-based glucose-responsive material, which
      forms a gel at low and a sol at high glucose concentrations. Results demonstrated
      that the device released insulin at a higher rate in response to glucose
      challenges. In contrast, a device containing an inert hydrogel instead of glucose
      responsive material released insulin at an essentially constant rate,
      irrespective of the surrounding glucose concentration. Necessary material
      improvements include increased sensitivity to glucose, so that the material
      responds to physiologically relevant glucose concentrations, and increased
      stability. The prospects of developing a properly functional, implantable
      substitute based on engineered non-beta cells and glucose-responsive material,
      and the material and device improvements that need to be made prior to in vivo
      experiments, are discussed.

PMID- 16440351
TI  - Does nucleolin bind the NF kappa B DNA binding motif?

PMID- 16440354
TI  - Comparison of different options for harvest of a therapeutic protein product from
      high cell density yeast fermentation broth.
AB  - Recovery of therapeutic protein from high cell density yeast fermentations at
      commercial scale is a challenging task. In this study, we investigate and compare
      three different harvest approaches, namely centrifugation followed by depth
      filtration, centrifugation followed by filter-aid enhanced depth filtration, and
      microfiltration. This is achieved by presenting a case study involving recovery
      of a therapeutic protein from Pichia pastoris fermentation broth. The focus of
      this study is on performance of the depth filtration and the microfiltration
      steps. The experimental data has been fitted to the conventional models for cake
      filtration to evaluate specific cake resistance and cake compressibility. In the
      case of microfiltration, the experimental data agrees well with flux predicted by
      shear induced diffusion model. It is shown that, under optimal conditions, all
      three options can deliver the desired product recovery ( >80%), harvest time (
      <15 h including sequential concentration/diafiltration step), and clarification (
      <6 NTU). However, the three options differ in terms of process development time
      required, capital cost, consumable cost, ease of scale-ability and process
      robustness. It is recommended that these be kept under consideration when making
      a final decision on a harvesting approach.

PMID- 16440356
TI  - HLA class I allelic diversity and progression of fibrosis in patients with
      chronic hepatitis C.
AB  - Patients infected with HIV-1 who are heterozygous at HLA class I loci present
      greater variety of antigenic peptides to CD8+ cytotoxic T lymphocytes, slowing
      progression to AIDS. A similar broad immune response in chronic hepatitis C (CHC)
      infection could result in greater hepatic injury. Although specific HLA class II
      alleles may influence outcome in CHC patients, the role of HLA class I
      heterogeneity is generally less clearly defined. Our aims were to determine
      whether HLA class I allelic diversity is associated with disease severity and
      progression of fibrosis in CHC. The study population consisted of 670 adults with
      CHC, including 155 with advanced cirrhosis, and 237 non-HCV-infected controls.
      Serological testing for HLA class I antigens was performed via
      microlymphocytotoxicity assay. Peptide expression was defined as heterozygous
      (i.e., a different allele at each locus) or homozygous. Fibrosis staging was
      determined using METAVIR classification. Heterozygosity at the B locus (fibrosis
      progression rate [FPR] 0.08 vs. 0.06 units/yr; P = .04) and homozygosity at the A
      locus (FPR 0.10 vs. 0.08 units/yr; P = .04) predicted a higher median FPR. Age at
      infection, genotype, and duration of infection were also predictors of FPR. A
      higher proportion of patients with stage F2-F4 expressed HLA-B18 compared with
      controls (OR 2.2, 95% CI 1.17-4.23; P = .02). These differences were not observed
      in patients with advanced cirrhosis. HLA zygosity at 1, 2, or 3 alleles was not
      associated with fibrosis stage, liver inflammation, or treatment outcome. In
      conclusion, HLA class I allelic diversity has a minor influence on FPRs and
      disease severity in CHC.

PMID- 16440357
TI  - A randomized controlled study of preemptive lamivudine in patients receiving
      transarterial chemo-lipiodolization.
AB  - Reactivation of hepatitis B virus (HBV) during chemotherapy is well documented.
      However, there are limited data on this complication in patients with
      hepatocellular carcinoma (HCC) undergoing transarterial chemotherapy. The aim of
      this study was to evaluate the efficacy of preemptive lamivudine therapy in
      reducing hepatitis due to HBV reactivation in patients with HCC undergoing
      transarterial chemo-lipiodolization (TACL) and to seek predictors of this event.
      A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m2
      and cisplatin 60 mg/m2 at monthly intervals were prospectively and randomly
      assigned to receive lamivudine 100 mg daily from the start of TACL (preemptive
      group) or not (control group). During the study, 11 (29.7%) of 37 patients in the
      control group and 1 (2.8%) of 36 patients in the preemptive group developed
      hepatitis due to HBV reactivation (P = .002). In addition, there were
      significantly more incidences of overall hepatitis (P = .021) and severe grade of
      hepatitis (P = .035) in the control group. With multivariate Cox regression
      model, a baseline HBV DNA level of more than 10(4) copies/mL was the only
      independent predictor of hepatitis due to HBV reactivation during chemo
      lipiodolization (P = .046). In conclusion, preemptive lamivudine therapy
      demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and
      hepatic morbidity during TACL. Preemptive therapy should be considered in HCC
      patients with an HBV DNA level of more than 10(4) copies/mL. Further studies are
      needed to confirm the value of this approach in patients with low-level viremia.

PMID- 16440358
TI  - Diagnostic value of FibroTest with normal serum aminotransferases.

PMID- 16440359
TI  - FibroScan and FibroTest to assess liver fibrosis in HCV with normal
      aminotransferases.

PMID- 16440360
TI  - Local ablation vs. resection for the treatment of hepatocellular carcinoma.

PMID- 16440361
TI  - Deaths on the liver transplant waiting list: an analysis of competing risks.
AB  - The usual method of estimating survival probabilities, namely the Kaplan-Meier
      method, is suboptimal in the analysis of deaths on the transplant waiting list.
      Death, transplantation, and withdrawal from list must all be considered. In this
      analysis, we applied the competing risk analysis method, which allows evaluating
      these end points individually and simultaneously, to compare the risk of waiting
      list death across era, blood types, liver disease diagnosis, and severity (Model
      for End-stage Liver Disease; MELD). Of 861 patients registered on the waiting
      list at Mayo Clinic Rochester between 1990 and 1999, 657 (76%) patients underwent
      transplantation, 82 (10%) died while waiting, 41 (5%) withdrew from the list, and
      81 (9%) patients were still waiting as of February 2002. The risk of death at 3
      years was 10% by the competing risk analysis. During the study period, the median
      time to transplantation increased from 45 to 517 days. In univariate analyses,
      there was no significant difference in the risk of death by era of listing (P =
      .25) or blood type (P = .31), whereas the risk of death was significantly higher
      in patients with alcohol-induced liver disease and those with higher MELD score
      (P < .01). A multivariable analysis showed that after adjusting for MELD, blood
      type, and diagnosis, patients listed in the latter era had higher mortality. In
      conclusion, the competing risk analysis method is useful in estimating the risk
      of death among patients awaiting liver transplantation.

PMID- 16440364
TI  - Long-term lamivudine therapy for children with HBeAg-positive chronic hepatitis
      B.
AB  - One year of lamivudine treatment results in increased hepatitis B e antigen
      (HBeAg) seroconversion and serum hepatitis B virus (HBV) DNA negativity in
      children with chronic hepatitis B and high serum alanine aminotransferase
      concentrations. Two hundred seventy-six children who participated in a 1-year
      randomized, placebo-controlled study of lamivudine were enrolled in a 24-month,
      open-label extension. Patients were stratified into two groups based on HBeAg
      status at week 48 of the previous study: 213 HBeAg-positive children were entered
      into a treatment arm, and 63 HBeAg-negative children were entered into an
      observation arm to evaluate durability of HBeAg loss. In the treatment arm, 28 of
      133 (21%) children previously treated with lamivudine and 23 of 77 (30%) children
      who previously received placebo achieved the primary end point: virological
      response (VR) (HBeAg loss and HBV DNA negativity) at month 24. The incidence of
      YMDD (tyrosine, methionine, aspartate, aspartate) mutations at month 24 was 64%
      (66/103) in the children previously treated with lamivudine and 49% (34/70) in
      those previously treated with placebo. The incidence of VR at month 24 was 5%
      (5/100) for patients with YMDD mutant HBV and 54% (39/72) for patients without.
      The durability of response in the observation arm was 89% (48/54) at month 24. In
      conclusion, further clinical response was seen over the 24-month open-label study
      period in children who had not initially achieved a VR after 12 months of
      lamivudine treatment. However, the incidence of YMMD mutations increased over
      time and resulted in lower response rates. VR was maintained in most patients who
      had initially responded to lamivudine in the first 12 months.

PMID- 16440362
TI  - Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism
      and alcoholic liver disease?
AB  - Case-control studies that have investigated the association between alcoholism
      and alcohol-induced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2
      polymorphisms have reported controversial or inconclusive results. Thus, we
      conducted a meta-analysis of 50 association studies of the above polymorphisms.
      We explored potential sources of heterogeneity and bias, performed subgroup
      analyses by racial background and sex, performed sensitivity analyses for studies
      not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases
      that met strict criteria for alcoholism. The present meta-analysis underscores
      significant associations of ADH2*1, ADH3*2, and ALDH2*1 alleles and the risk of
      alcoholism (OR = 1.89 [95% CI 1.56-2.28], 1.32 [95% CI 1.12-1.57], and 4.35 [95%
      CI 3.04-6.23], respectively). The subsequent subgroup analyses showed association
      for ADH2*1 and ADH3*2 only in East Asians (OR = 2.23 [95% CI 1.81-2.74] and 1.91
      [95% CI 1.45-2.53], respectively) and East Asian males (OR = 2.21 [95% CI 1.57
      3.10], 1.69 [95% CI 1.10-2.59], respectively). In East Asian males, the OR for
      ALDH2*1 was 3.66 (95% CI 1.68-7.96). In Caucasians, sensitivity analysis revealed
      an association for ADH2*1 in alcoholism (OR = 1.62 [95% CI 1.22-1.89]). When
      strict criteria were imposed, the pattern of results remained unaltered. For
      liver disease, there were no significant associations for ADH2*1, ADH3*2, or
      ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association
      whatsoever. There is evidence that alleles are mainly dominant. In conclusion,
      there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2,
      and lack of bias in all polymorphisms. The above findings reinforce the need for
      more rigorous studies, and for regular synthesis of studies' results.

PMID- 16440365
TI  - Acute hepatitis C: in search of the optimal approach to cure.

PMID- 16440366
TI  - Diagnosis, prevention and management of hepatitis B virus reactivation during
      anticancer therapy.

PMID- 16440367
TI  - Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C
      infection: the HEP-NET acute-HCV-II study.
AB  - Early treatment of acute hepatitis C with interferon alpha-2b for 24 weeks
      prevents chronic infection in almost all patients. Because pegylated interferons
      have replaced conventional interferon in the therapy of chronic hepatitis C, the
      aim of this study was to analyze the efficacy of an early treatment of acute
      hepatitis C with peginterferon alpha-2b. Between February 2001 and February 2004,
      89 individuals with acute HCV infection were recruited at 53 different centers in
      Germany. Patients received 1.5 microg/kg peginterferon alpha-2b for 24 weeks;
      treatment was initiated after a median of 76 days after infection (range 14-150).
      End-of-treatment response and sustained virological response were defined as
      undetectable HCV RNA at the end of therapy and after 24 weeks of follow-up,
      respectively. In the total study population, virological response was 82% at the
      end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%)
      were adherent to therapy, receiving 80% of the interferon dosage within 80% of
      the scheduled treatment duration. End-of-treatment and sustained virological
      response rates in this subpopulation were 94% and 89%, respectively. A maximum
      alanine aminotransferase level of more than 500 U/L prior to therapy was the only
      factor associated with successful treatment. In conclusion, in acute HCV
      infection, early treatment with peginterferon alpha-2b leads to high virological
      response rates in individuals who are adherent to treatment. The high number of
      dropouts underlines the importance of thorough patient selection and close
      monitoring during therapy. Thus, future studies should identify factors
      predicting spontaneous viral clearance to avoid unnecessary therapy.

PMID- 16440368
TI  - Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate
      dependent and involves AE2 anion exchanger.
AB  - Canalicular bile is modified along bile ducts through reabsorptive and secretory
      processes regulated by nerves, bile salts, and hormones such as secretin.
      Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator
      (CFTR)-dependent Cl- efflux and subsequent biliary HCO3- secretion, possibly via
      Cl-/HCO3- anion exchange (AE). However, the contribution of secretin to bile
      regulation in the normal rat, the significance of choleretic bile salts in
      secretin effects, and the role of Cl-/HCO3- exchange in secretin-stimulated HCO3-
      secretion all remain unclear. Here, secretin was administered to normal rats with
      maintained bile acid pool via continuous taurocholate infusion. Bile flow and
      biliary HCO3- and Cl- excretion were monitored following intrabiliary retrograde
      fluxes of saline solutions with and without the Cl- channel inhibitor 5-nitro-2
      (3-phenylpropylamino)-benzoic acid (NPPB) or the Cl-/HCO3- exchange inhibitor
      4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Secretin increased
      bile flow and biliary excretion of HCO3- and Cl-. Interestingly, secretin effects
      were not observed in the absence of taurocholate. Whereas secretin effects were
      all blocked by intrabiliary NPPB, DIDS only inhibited secretin-induced increases
      in bile flow and HCO3- excretion but not the increased Cl- excretion, revealing a
      role of biliary Cl-/HCO3- exchange in secretin-induced, bicarbonate-rich
      choleresis in normal rats. Finally, small hairpin RNA adenoviral constructs were
      used to demonstrate the involvement of the Na+-independent anion exchanger 2
      (AE2) through gene silencing in normal rat cholangiocytes. AE2 gene silencing
      caused a marked inhibition of unstimulated and secretin-stimulated Cl-/HCO3-
      exchange. In conclusion, maintenance of the bile acid pool is crucial for
      secretin to induce bicarbonate-rich choleresis in the normal rat and that this
      occurs via a chloride-bicarbonate exchange process consistent with AE2 function.

PMID- 16440369
TI  - C/EBPalpha and HNF6 protein complex formation stimulates HNF6-dependent
      transcription by CBP coactivator recruitment in HepG2 cells.
AB  - We previously demonstrated that formation of complexes between the DNA-binding
      domains of hepatocyte nuclear factor 6 (HNF6) and forkhead box a2 (Foxa2)
      proteins stimulated Foxa2 transcriptional activity. Here, we used HepG2 cell
      cotransfection assays to demonstrate that HNF6 transcriptional activity was
      stimulated by CCAAT/enhancer-binding protein alpha (C/EBPalpha), but not by the
      related C/EBPbeta or C/EBPdelta proteins. Formation of the C/EBPalpha-HNF6
      protein complex required the HNF6 cut domain and the C/EBPalpha activation domain
      (AD) 1/AD2 sequences. This C/EBPalpha-HNF6 transcriptional synergy required both
      the N-terminal HNF6 polyhistidine and serine/threonine/proline box sequences, as
      well as the C/EBPalpha AD1/AD2 sequences, the latter of which are known to
      recruit the CREB binding protein (CBP) transcriptional coactivator. Consistent
      with these findings, adenovirus E1A-mediated inhibition of p300/CBP histone
      acetyltransferase activity abrogated C/EBPalpha-HNF6 transcriptional synergy in
      cotransfection assays. Co-immunoprecipitation assays with liver protein extracts
      demonstrate an association between the HNF6 and C/EBPalpha transcription factors
      and the CBP coactivator protein in vivo. Furthermore, chromatin
      immunoprecipitation assays with hepatoma cells demonstrated that increased levels
      of both C/EBPalpha and HNF6 proteins were required to stimulate association of
      these transcription factors and the CBP coactivator protein with the endogenous
      mouse Foxa2 promoter region. In conclusion, formation of the C/EBPalpha-HNF6
      protein complex stimulates recruitment of the CBP coactivator protein for
      expression of Foxa2, a transcription factor critical for regulating expression of
      hepatic gluconeogenic genes during fasting.

PMID- 16440370
TI  - Protein chip based miniaturized assay for the simultaneous quantitative
      monitoring of cancer biomarkers in tissue extracts.
AB  - A multiplexed fluorescence immunoassay using a novel planar waveguide technology
      based microarray system, ZeptoMARK (Zeptosens), was developed to detect
      simultaneously urokinase-type plasminogen activator (uPA), plasminogen activator
      inhibitor-1 (PAI-1), and vascular endothelial growth factor (VEGF) in extracts of
      breast cancer tissues. The three analytes assay was cross-validated with single
      analyte ELISA/chemiluminescence immunosorbent assay tests, revealing good
      correlations and enhanced assay sensitivities (LODs) of 1 pg/mL for uPA, 33 pg/mL
      for PAI-1, and 1 pg/mL for VEGF. Values were well within the 80-120% limits for
      assay recovery and within the +/-20% limits for assay precision. The uPA, PAI-1,
      and VEGF results obtained from 50 breast cancer cytosols using the protein array
      system demonstrated that the microarray-based multiplexed assay is a sensitive
      and robust tool to be used for the simultaneous quantification of cancer markers
      in small breast cancer tissue samples (core biopsies). The miniaturized,
      multiplexed assay format has a potential to be used for the quantitative analysis
      of a larger set of validated markers with significance in disease management.

PMID- 16440371
TI  - Salt stress adaptation of Bacillus subtilis: a physiological proteomics approach.
AB  - The adaptation to osmotic stress is crucial for growth and survival of Bacillus
      subtilis in its natural ecosystem. Dual channel imaging and warping of 2-D
      protein gels were used to visualize global changes in the protein synthesis
      pattern of cells in response to osmotic stress (6% NaCl). Many vegetative enzymes
      were repressed in response to salt stress and derepressed after resumption of
      growth. The enzymes catalyzing the metabolic steps from glucose to 2
      oxoglutarate, however, were almost constantly synthesized during salt stress
      despite the growth arrest. This indicates an enhanced need for the proline
      precursor glutamate. The synthesis of enzymes involved in sulfate assimilation
      and in the formation of Fe-S clusters was also induced, suggesting an enhanced
      need for the formation or repair of Fe-S clusters in response to salt stress. One
      of the most obvious changes in the protein synthesis profile can be followed by
      the very strong induction of the SigB regulon. Furthermore, members of the SigW
      regulon and of the PerR regulon, indicating oxidative stress after salt
      challenge, were also induced. This proteomic approach provides an overview of
      cell adaptation to an osmotic upshift in B. subtilis visualizing the most
      dramatic changes in the protein synthesis pattern.

PMID- 16440372
TI  - Personality trait of harm avoidance in late-life depression.

PMID- 16440373
TI  - Neuroleptic malignant like syndrome in two patients on cholinesterase inhibitors.

PMID- 16440374
TI  - Expanding the genetic code in a mammalian cell line by the introduction of four
      base codon/anticodon pairs.

PMID- 16440375
TI  - Genetic targeting of individual cells with a voltage-sensitive dye through
      enzymatic activation of membrane binding.
AB  - Optical recording of the electrical activity of individual neurons in culture or
      in a tissue requires cell-selective staining with a fluorescent voltage-sensitive
      dye. In a proof-of-principle experiment, we implement a novel approach to
      genetically targeted staining. The method relies on a water-soluble precursor dye
      and an overexpressed cell-surface enzyme that transforms the precursor into a
      hydrophobic dye that binds to the targeted cell. We fused an alkaline phosphatase
      to a specifically designed general-purpose membrane anchor, and the fusion
      protein was expressed on the surface of HEK293 cells, as was corroborated by
      immuno- and histochemical staining. We next synthesised an amphiphilic
      hemicyanine dye containing two enzymatically cleavable phosphate groups at its
      hydrocarbon tails. When the phosphate groups were removed, the binding to
      membranes was enhanced by a factor of a thousand, as shown by titration with
      lipid vesicles. We observed selective staining of enzymatically active cells by
      fluorescence microscopy in a mixed population of phosphatase-transfected and
      untransfected HEK293 cells. The critical parameters of enzyme-induced cell
      selective staining were elucidated by a simple kinetic model to guide further
      developments of the method.

PMID- 16440376
TI  - Label-free biosensing with hydrogel microlenses.

PMID- 16440377
TI  - Laser-induced acoustic desorption mass spectrometry of single bioparticles.

PMID- 16440378
TI  - A highly regioselective salt-free iron-catalyzed allylic alkylation.

PMID- 16440379
TI  - Elementary arithmetic operations by enzymes: a model for metabolic pathway based
      computing.

PMID- 16440380
TI  - Ultrasensitive detection of proteins by amplification of affinity aptamers.

PMID- 16440381
TI  - Electrochemical enol ether/olefin cross-metathesis in a lithium
      perchlorate/nitromethane electrolyte solution.

PMID- 16440382
TI  - Circular-polarization-induced enantiomeric excess in liquid crystals of an
      achiral, bent-shaped mesogen.

PMID- 16440383
TI  - Ligand-directed strategy for zeolite-type metal-organic frameworks: zinc(II)
      imidazolates with unusual zeolitic topologies.

PMID- 16440384
TI  - Enantioselective catalysis and analysis on a chip.

PMID- 16440386
TI  - Fluorine segregation in crystalline materials: structural control and solid-state
      [2+2] cycloaddition in CF(3)-substituted tetrathiafulvalene derivatives.
AB  - The well-known influence of long perfluorinated chains on the structures and
      stability of amphiphilic molecules in liquid crystalline mesophases or mesoscopic
      micellar arrangements is evaluated here in the realm of crystalline materials
      based on rigid aromatic molecules bearing only a limited number of CF(3)
      moieties. Tetrathiafulvalene (TTF) derivatives bearing one or two CF(3) groups,
      that is, (Z)- and (E)-(CF(3))(2)TTF ((Z)-1, (E)-1), EDT-TTF-CF(3) (2), and EDT
      TTF(CF(3))(2) (3) (EDT=ethylenedithio) are prepared from the 1,3-dipolar reaction
      of methyl 4,4,4-trifluorotetrolate with ethylenetrithiocarbonate. The structures
      of neutral (Z)-1, (E)-1, 2, and 3 as indicated by single-crystal X-ray
      diffraction measurements reveal the recurrent formation of layered structures
      with a strong segregation of the fluorinated moieties and formation of fluorous
      bilayers, attributed to the amphiphilic character of those TTF derivatives upon
      CF(3) functionalization, and without need for longer C(n)F(2n+1) (n>1)
      perfluorinated chains. The short intermolecular distance between outer C==C
      double bonds observed in the layered structure of (E)-1 allows a solid-state
      [2+2] photocyclization with formation of chiral dyads incorporating the
      characteristic cyclobutane ring. These dyads containing two
      dihydrotetrathiafulvalene moieties facing each other exhibit reversible oxidation
      to the mixed-valence radical cation state and organize in the solid-state into
      the same layered structures with fluorous bilayers.

PMID- 16440385
TI  - Recovery of homogeneous polyoxometallate catalysts from aqueous and organic media
      by a mesoporous ceramic membrane without loss of catalytic activity.
AB  - The recovery of homogeneous polyoxometallate (POM) oxidation catalysts from
      aqueous and non-aqueous media by a nanofiltration process using mesoporous gamma
      alumina membranes is reported. The recovery of Q(12)[WZn(3)(ZnW(9)O(34))(2)]
      (Q=[MeN(n-C(8)H(17))(3)](+)) from toluene-based media was quantitative within
      experimental error, while up to 97 % of Na(12)[WZn(3)(ZnW(9)O(34))(2)] could be
      recovered from water. The toluene-soluble POM catalyst was used repeatedly in the
      conversion of cyclooctene to cyclooctene oxide and separated from the product
      mixture after each reaction. The catalytic activity increased steadily with the
      number of times that the catalyst had been recycled, which was attributed to
      partial removal of the excess QCl that is known to have a negative influence on
      the catalytic activity. Differences in the permeability of the membrane for
      different liquid media can be attributed to viscosity differences and/or
      capillary condensation effects. The influence of membrane pore radius on
      permeability and recovery is discussed.

PMID- 16440387
TI  - Polymorphism versus thermochromism: interrelation of color and conformation in
      overcrowded bistricyclic aromatic enes.
AB  - The nature of the thermochromic form of overcrowded bistricyclic aromatic enes
      (BAEs) has been controversial for a century. We report the single-crystal X-ray
      structure analysis of the deep-purple and yellow polymorphs of 9-(2,7-dimethyl-9H
      fluoren-9-ylidene)-9H-xanthene (11), which revealed the molecules in a twisted
      and a folded conformation, respectively. Therefore, the deeply colored
      thermochromic form B of BAEs is identified as having a twisted conformation and
      the ambient-temperature form A as having a folded conformation. This relationship
      between the color and the conformation is further supported by the X-ray
      structures of the deep-purple crystals of the twisted 9-(9H-fluoren-9-ylidene)-9H
      xanthene (10), and of the yellow crystals of the folded 9-(11H-benzo[b]fluoren-11
      ylidene)-9H-xanthene (12). Based on this conclusive crystallographic evidence,
      eleven previously proposed rationales of thermochromism in BAEs are refuted. In
      the twisted structures, the tricyclic moieties are nearly planar and the central
      double bond is elongated to 1.40 A and twisted by 42 degrees . In the folded
      structures, the xanthylidene moieties are folded by 45 degrees and the
      fluorenylidene moieties by 18-20 degrees . Factors stabilizing the twisted and
      folded conformations are discussed, including twisting of formal single or double
      bonds, intramolecular overcrowding, and the significance of a dipolar aromatic
      "xanthenylium-fluorenide" push-pull structure.

PMID- 16440388
TI  - Anellated N-heterocyclic carbenes: 1,3-dineopentylnaphtho[2,3-d]imidazol-2
      ylidene: synthesis, KOH addition product, transition-metal complexes, and
      anellation effects.
AB  - Two novel anellated N-heterocyclic carbenes (NHC), 1,3-dineopentylnaphtho[2,3
      d]imidazol-2-ylidene, and 1,3-dineopentyl-2-ylido-imidazolo[4,5-b]pyridine were
      obtained by reduction of the respective thiones with potassium, the former also
      by deprotonation of the corresponding naphthimidazolium hexafluorophosphate by
      using excess KH in THF. The use of equimolar amounts of KH provided an unexpected
      formal addition product of this NHC with KOH. X-ray crystal structure analysis of
      the adduct provided evidence for a distorted tetrameric N-heterocyclic alkoxide,
      stabilized by two THF molecules. In C(6)D(6) the compound undergoes
      disproportionation. Transition-metal complexes [(NHC)AgCl], [(NHC)Rh(cod)Cl], and
      (E)-[(NHC)(2)PdCl(2)] of the novel naphthimidazol-2-ylidene were synthesized. X
      ray crystal structures and (1)H and (13)C NMR spectroscopic data provided
      detailed structural information. Comparing characteristic data with those of
      nonanellated and differently anellated NHCs or their complexes provides
      information on the influence of the extended anellation.

PMID- 16440389
TI  - Catalytic enantioselective three-component hetero-[4+2]
      cycloaddition/allylboration approach to alpha-hydroxyalkyl pyrans: scope,
      limitations, and mechanistic proposal.
AB  - This article describes the design and optimization of a catalytic
      enantioselective three-component hetero-[4+2] cycloaddition/allylboration
      reaction between 3-boronoacrolein, enol ethers, and aldehydes to afford alpha
      hydroxyalkyl dihydropyrans. The key substrate, 3-boronoacrolein pinacolate (2)
      was found to be an exceptionally reactive heterodiene in the hetero-[4+2]
      cycloaddition catalyzed by Jacobsen's chiral Cr(III) catalyst 1. The scope and
      limitations of this process were thoroughly examined. The adduct of 3
      boronoacrolein pinacolate and ethyl vinyl ether was obtained in high yield and
      with over 95 % enantioselectivity. This cyclic alpha-chiral allylboronate adds to
      a very wide variety of aldehyde substrates, including unsaturated aldehydes and
      alpha-chiral aldehydes to give diastereomerically pure products. Acyclic 2
      substituted enol ethers can be employed, in which case the catalyst promotes a
      kinetically selective reaction that favors Z enol ethers over the E isomers.
      Surprisingly, 3-boronoacrolein pinacolate was found to be a superior heterodiene
      than ethyl (E)-4-oxobutenoate, and a mechanistic interpretation based on a
      possible [5+2] transition state is proposed.

PMID- 16440390
TI  - Ruthenium-catalyzed asymmetric epoxidation of olefins using H2O2, part I:
      synthesis of new chiral N,N,N-tridentate pybox and pyboxazine ligands and their
      ruthenium complexes.
AB  - The synthesis of chiral tridentate N,N,N-pyridine-2,6-bisoxazolines 3 (pybox
      ligands) and N,N,N-pyridine-2,6-bisoxazines 4 (pyboxazine ligands) is described
      in detail. These novel ligands constitute a useful toolbox for the application in
      asymmetric catalysis. Compounds 3 and 4 are conveniently prepared by cyclization
      of enantiomerically pure alpha- or beta-amino alcohols with dimethyl pyridine-2,6
      dicarboximidate. The corresponding ruthenium complexes are efficient asymmetric
      epoxidation catalysts and have been prepared in good yield and fully
      characterized by spectroscopic means. Four of these ruthenium complexes have been
      characterized by X-ray crystallography. For the first time the molecular
      structure of a pyboxazine complex [2,6-bis-[(4S)-4-phenyl-5,6-dihydro-4H
      [1,3]oxazinyl]pyridine](pyridine-2,6-dicarboxylate)ruthenium (S)-2 aa, is
      presented.

PMID- 16440391
TI  - Electronic properties and reactivity of short-chain oligomers of 3,4
      phenylenedioxythiophene (PheDOT).
AB  - The dimer and trimer of 3,4-phenylenedioxythiophene (PheDOT) have been
      synthesized. Unlike the parent systems based on 3,4-ethylenedioxythiophene
      (EDOT), these compounds are quite stable under atmospheric conditions. The
      electronic absorption spectra of di- and tri-PheDOT exhibit a well-resolved
      vibronic fine structure indicative of self-rigidification of the conjugated
      structure by noncovalent intramolecular sulfur-oxygen interactions. Comparison of
      UV-visible data for the PheDOT oligomers with those of the corresponding EDOT
      oligomers reveals a faster decrease of the HOMO-LUMO gap with chain length for
      the former. Cyclic voltammetric data show that whereas PheDOT oxidizes at a lower
      potential than EDOT, the PheDOT dimer and trimer exhibit much higher oxidation
      potentials than their EDOT-based analogues. A comparative analysis of the
      electropolymerization of the three PheDOT-based systems shows that although
      PheDOT is very difficult to polymerize, its dimer and trimer can be readily
      electropolymerized. This unexpected increase of reactivity with chain extension
      is discussed with the aid of theoretical calculations.

PMID- 16440392
TI  - Structurally characterized hetero-oligopolyphenylenes: synthetic advances toward
      next-generation heterosuperbenzenes.
AB  - The successful Diels-Alder [2+4] cycloaddition of dipyrimidyl acetylene and
      suitably substituted 2,3,4,5-tetraarylcyclopenta-2,4-dien-1-ones (3-7) generates
      a series of selectively functionalized hexaarylbenzenes. Each has two pairs of
      peripheral functional groups (R' and R=tert-butyl 8 and R=methyl 9, methoxy 10,
      bromo 11, triisopropylsilylethynyl 12) and four ortho-imine nitrogen atoms. The
      dibromo derivative 11 is a useful precursor for the formation of a mono ethynyl
      13 and diethynyl 14 substituted polyphenylene. Changing the dienophile to di(2
      thienyl)acetylene gives an S-heteroatom polyphenylene 15. The compounds were
      fully characterized by using (1)H, (13)C and a range of 2 D NMR spectroscopic
      techniques, elemental analysis, and mass spectrometry. Oxidative
      cyclodehydrogenation of dimethoxy hexaphenylbenzene 10 by using iron(III)
      chloride results in the formation of a spirocyclic dienone 16, which in a
      separate reaction undergoes dienone/phenol rearrangement to give the first 4
      fused-ring, N-heterosuperbenzene (HSB) 17. Six single crystal molecular
      structures reveal the commonality of unidirectional twisting of the external
      aromatic rings in these heteroatom polyphenylenes. The twist angles and any H
      bonding or interdigitation in these structures are discussed.

PMID- 16440393
TI  - The importance of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo-dipeptide
      catalyzed enantioselective transfer hydrogenation of ketones.
AB  - We studied the role of alkali cations in the [{RuCl2(p-cymene)}2]-pseudo
      dipeptide-catalyzed enantioselective transfer hydrogenation of ketones with
      isopropanol. Lithium salts were shown to increase the enantioselectivity of the
      reaction when iPrONa or iPrOK was used as the base. Similar transfer
      hydrogenation systems that employ chiral amino alcohol or monotosylated diamine
      ligands are not affected by the addition of lithium salts. These observations
      have led us to propose that an alternative reaction mechanism operates in pseudo
      dipeptide-based systems, in which the alkali cation is an important player in the
      ligand-assisted hydrogen-transfer step. DFT calculations of the proposed
      transition-state (TS) models involving different cations (Li+, Na+, and K+)
      confirm a considerable loosening of the TS with larger cations. This loosening
      may be responsible for the fewer interactions between the substrate and the
      catalytic complex, leading to lower enantiodifferentiation. This mechanistic
      hypothesis has found additional experimental support; the low ee obtained with
      [BnNMe3]OH (a large cation) as base can be dramatically improved by introducing
      lithium cations into the system. Also, the complexation of Na+, K+, and Li+
      cations by the addition of [15]crown-5 and [18]crown-6 ethers and cryptand 2.1.1
      (which selectively bind to these cations and, thus, increase their bulkiness),
      respectively, to the reaction mixture led to a significant drop in the
      enantioselectivity of the reaction. The lithium effect has proved useful for
      enhancing the reduction of different aromatic and heteroaromatic ketones.

PMID- 16440394
TI  - Site-selective protein immobilization by Staudinger ligation.

PMID- 16440395
TI  - Biologically driven assembly of polyelectrolyte microcapsule patterns to
      fabricate microreactor arrays.

PMID- 16440396
TI  - The Alpher, Bethe, Gamow of isoelectric focusing, the alpha-Centaury of
      electrokinetic methodologies. Part I.
AB  - The birth and evolution of IEF in conventional carrier ampholyte buffers is
      reviewed here, from a shaky start during World War II, via desperate attempts of
      Svensson to create pH gradients by stationary electrolysis of salts, to the
      development of the IEF theory and the solution of the steady-state equation. The
      remarkable synthetic process of Ampholines, as ingeniously devised by Vesterberg,
      is additionally recalled, with a thorough description of the fundamental
      properties of these amphoteric buffers, creating and maintaining the pH gradient
      under strong electric fields. The review ends with a mention of the major
      contributions of B. J. Radola to this field, namely analytical and preparative
      IEF in granulated Sephadex layers and the development of ultrathin IEF, in
      polyacrylamide gels as thin as 20-100 mum. The latter technique paved the way to
      DNA sequencing gels and to CZE. The symptoms of decay are here presented through
      the simulations of Mosher and Thormann, clearly indicating an isotachophoretic
      mechanism for pH gradient decay with time. The decay of IEF was the birth of
      IPGs.

PMID- 16440397
TI  - Curved DNA molecules migrate anomalously slowly in polyacrylamide gels even at
      zero gel concentration.
AB  - The electrophoretic mobilities of curved and normal DNA molecules of the same
      size have been measured in polyacrylamide gels containing various acrylamide
      concentrations and cross-linker ratios. Ferguson plots were constructed to
      extrapolate the observed mobilities to zero gel concentration. The DNA samples
      were two 147-bp restriction fragments, called 12A and 12B, obtained from the MspI
      digestion of plasmid pBR322, and head-to-tail multimers of each fragment.
      Fragment 12A is stably curved and migrates anomalously slowly in polyacrylamide
      gels; fragment 12B has the conformation of normal DNA and migrates with normal
      electrophoretic mobilities. The extrapolated mobilities of the curved fragment
      12A and its multimers at zero gel concentration are lower than the extrapolated
      mobilities of the normal fragment 12B and its multimers. The free solution
      mobility of the curved fragment 12A, measured by CE, is also lower than that of
      the normal fragment 12B. The combined results indicate that the extrapolated
      mobilities observed for curved DNA molecules at zero polyacrylamide gel
      concentration reflect the intrinsic differences in their free solution
      mobilities.

PMID- 16440398
TI  - Comparison of the use of anionic and cationic surfactants for the separation of
      steroids based on MEKC and sweeping-MEKC modes.
AB  - In attempts to improve the selectivity and sensitivity of steroid separation and
      to determine their migration order, a comparison of the use of anionic and
      cationic surfactants based on the MEKC and sweeping-MEKC modes was made. A
      mixture of six steroids (progesterone, 17-hydroxy progesterone, 11-deoxycortisol,
      corticosterone, cortisone, and cortisol) could be separated and detected by means
      of the CE/UV-absorption method. The order of migration time for these steroids
      was compared under various conditions, including acidic/alkaline buffers,
      anionic/cationic surfactants, and positive/negative applied voltage, causing the
      direction of the EOF and the migration of micelles to change. The major rules for
      generally predicting the migration order of steroids are summarized. The
      detection limits were significantly improved when the sweeping-MEKC mode was
      applied.

PMID- 16440399
TI  - Determination of antidepressants in surface and waste water samples by capillary
      electrophoresis with electrospray ionization mass spectrometric detection after
      preconcentration using off-line solid-phase extraction.
AB  - A method for the quantitative determination of seven major antidepressants in
      surface waters and sewage treatment plant effluents by CE using ESI-MS is
      presented. Calibration curves for the selected analytes were prepared in Milli-Q
      purified water and Danube river water extract covering a concentration range of
      at least one order of magnitude. LODs achieved were between 6 and 13 microg/L for
      Trazodone and 39 and 53 microg/L for Sertraline in the Milli-Q purified water and
      Danube river water matrix, respectively. For sample preparation eight different
      SPE materials were investigated. Best results were obtained for a resin based on
      hydrophilic divinylbenzene (recoveries from Milli-Q purified water 93-96%; from
      Danube river water 85-99%). Finally, a series of eight sewage treatment plant
      effluents were investigated with respect to their content in the selected
      antidepressants. Six of these samples were tested positive for antidepressants,
      in particular Venlafaxine, Citalopram and Trazodone in concentrations between 36
      and 322 ng/L.

PMID- 16440400
TI  - Platinum group metallodrug-protein binding studies by capillary electrophoresis -
      inductively coupled plasma-mass spectrometry: a further insight into the
      reactivity of a novel antitumor ruthenium(III) complex toward human serum
      proteins.
AB  - Biochemical speciation analysis has become a hot area of CE research due largely
      to growing emergence of inductively coupled plasma (ICP)-MS as a proper detection
      technique. A benefit of CE-ICP-MS coupling in species-selective analysis of
      anticancer metal-based drugs is the possibility of distinguishing the signals of
      the intact drug and its metabolites and hence of quantifying them independently.
      This advantage (over CE with UV-vis detection) was exploited here in order to
      gain better knowledge about the rate and degree of the transformation of
      indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019), a
      promising tumor-inhibiting agent that successfully finished phase I clinical
      studies, upon its binding toward individual serum transport proteins. At
      increasing the KP1019/protein molar ratio, the reaction rate expressed by an
      evolving peak of the protein adduct became faster, with the equilibrium state
      being reached after about 40 and 60 min of incubation at 37 degrees C for
      transferrin and albumin, respectively. The binding reaction was shown to obey the
      first-order character that enabled for reliable calculation of the corresponding
      rate constants as (28.7 +/- 1.5) x 10(-4) and (10.6 +/- 0.7) x 10(-4)/s,
      respectively. When incubated with a ten-fold excess of KP1019, albumin and
      transferrin bound, respectively, up to 8 and 10 equiv. of ruthenium (Ru).
      Relative affinity of KP1019 toward different proteins under simulated
      physiological conditions was also characterized in terms of the overall binding
      constants (5600 and 10 600/M, respectively). To emphasize the difference in the
      protein-binding behavior, a competitive interaction of KP1019 was followed by CE
      ICP-MS at the actual molar ratio of proteins in blood, i.e. a ten-fold excess of
      albumin over transferrin. The fact that KP1019 binds to albumin stronger than to
      transferrin was manifested by finding almost all ruthenium (98-99%) in the
      albumin fraction.

PMID- 16440401
TI  - Fluorescence imaging of sample zone narrowing and dispersion in a glass
      microchip: the effects of organic solvent (acetonitrile)-salt mixtures in the
      sample matrix and surfactant micelles in the running buffer.
AB  - A mismatch in the EOF velocities between the sample zone and running buffer
      region is known to generate pressure-driven, parabolic flow profile of the sample
      plug in electrokinetic separation systems. In the present study, video
      fluorescence microscopy was employed to capture real-time dynamics of the sample
      plug (containing fluorescein as the probe molecule) in a discontinuous
      conductivity system within a glass microchip, in which the sample matrix
      consisted of a mixture of ACN and salt (NaCl), and the running buffer contained
      sodium cholate (SC) micelles as the pseudo-stationary phase (i.e., performing
      "ACN stacking" in the mode of MEKC). Upon application of the separation voltage,
      the video images revealed that zone narrowing and broadening of the probe
      molecules occurred as the sample plug headed toward the cathode during the
      initial time period, probably resulting in part from the stacking/sweeping, and
      destacking of the SC micelles at the boundaries between the sample zone and
      running buffer. Interestingly, a second sample zone narrowing event can be
      observed as the sample plug moved further toward the cathode, which could be
      attributed to the sweeping of the slower moving probe molecules by the faster
      moving SC micelles that originated from the anode. This phenomenon was studied as
      a function of pH, sample plug length, as well as the concentration of organic
      solvent and salt in the sample matrix. The data suggested that the presence of
      large amounts of an organic solvent (such as ACN or methanol) and salts in the
      sample matrix not only induces sample dispersion due to the formation of a
      pressure-driven (hydrodynamic) flow, but may also lead to the formation of a
      double sample zone narrowing phenomenon by altering the local EOF dynamics within
      the separation system.

PMID- 16440402
TI  - Capillary electrophoretic chiral separation of hydroxychloroquine and its
      metabolites in the microsomal fraction of liver homogenates.
AB  - A rapid, selective, and low-cost chiral capillary electrophoretic method was
      developed for the simultaneous analysis of hydroxychloroquine (HCQ) and its three
      chiral metabolites: desethylchloroquine (DCQ), desethylhydroxychloroquine (DHCQ),
      and bisdesethylchloroquine (BDCQ) in the microsomal fraction of liver
      homogenates. After liquid-liquid extraction using toluene as extracting solvent,
      the drug and metabolites were resolved on a fused-silica capillary (50 microm ID,
      50 cm total length, and 42 cm effective length), using 100 mmol/L of
      Tris/phosphate buffer, pH 9.0 containing 1% w/v sulfated-beta-CD and 30 mg/mL
      hydroxypropyl-beta-CD. Detection was carried out at 220 nm. The extraction
      procedure was efficient in removing endogenous interferents, and low values
      (<or=15%) for CVs and deviation from theoretical values were demonstrated for
      both within-day and between-day assays. The quantitation limit was 125 ng/mL with
      linear response over the 125-2000 ng/mL of concentration range for all
      metabolites. After validation, the method was used for an in vitro metabolism
      study of HCQ. The major HCQ metabolite formed by microsomal enzymes was (-)-(R)
      DHCQ.

PMID- 16440403
TI  - The added value of a multidisciplinary approach in diagnosing dementia: a review.
AB  - BACKGROUND: The impact of dementia constitutes a major public health challenge to
      our society. A multidisciplinary approach to dementia is generally recommended.
      OBJECTIVE: The objective of this review is to give an overview of the reported
      empirical studies on the added value of a multidisciplinary approach to
      diagnosing dementia, i.e. whether differences can be found between diagnostic
      multidisciplinary approaches, and/or monodisciplinary ones with respect to the
      diagnostic outcomes, the impact of diagnostics and their effects on quality of
      life and costs. METHOD: Critical review of studies which involve a
      multidisciplinary assessment of dementia. Literature was systematically searched
      in a number of international databases (Medline, PsychInfo, Pubmed and EconLit).
      A first selection was based on screening titles by one author. Interrater
      reliability was determined by scoring all abstracts by two authors. The
      reliability of selecting full articles was based on scoring a random sample by
      two authors. Kappa values were calculated. The Kappa statistic (k) was also used
      as an indicator of the diagnostic agreement between single disciplines and
      multidisciplinary teams. RESULTS: Five studies were identified as relevant for
      the purpose of this review. The most important outcome was the level of
      diagnostic agreement between single disciplines and multidisciplinary teams
      (MTs). Overall, there was substantial agreement (kappa: 0.37-0.76) on the
      diagnosis dementia (syndrome), but not on the subtypes (aetiology) (AD: 0.26
      0.60; VD: 0.35-0.52; depression: 0.30-0.46). Diagnoses also differed between the
      disciplines. CONCLUSIONS: Merely studies on diagnostic accuracy were found, all
      using different reference standards. Kappa values were chosen as outcome measure
      and every diagnosis was considered of equal value. Therefore, the added value
      could not definitively be demonstrated. However, the potential added value of a
      multidisciplinary approach to diagnosing dementia probably lies in the ability to
      differentiate among the subtypes of dementia and to detect comorbid psychiatric
      conditions such as depression. Disciplines within an MT complement each other in
      establishing a specific diagnosis, which is considered to be the added value of
      such a multidisciplinary team.

PMID- 16440404
TI  - Risk of depression in patients with chronic respiratory diseases: results from
      two large cohort studies in Chinese elderly from Hong Kong.
AB  - OBJECTIVE: Although it has been suggested that depression is common in patients
      with chronic respiratory diseases such as chronic obstructive pulmonary disease
      (COPD), few studies on the association between chronic respiratory diseases and
      depression have been conducted in the community. METHOD: Data from the baseline
      examination of two cohort studies, Mr and Ms Os, Hong Kong were used. Three
      thousand nine hundred and ninety-eight Hong Kong men and women aged 65 to 92 were
      recruited. Depression was assessed by face-to-face interview, using the short
      form of a validated Chinese version of the Geriatric Depression Scale (GDS).
      Chronic respiratory disease was assessed by subjects' self reports of chronic
      respiratory disease (chronic bronchitis, emphysema and asthma) diagnosed by
      medical doctors. Adjusted odds ratios (ORs) and corresponding 95% confidence
      intervals (CI) for depression among subjects with chronic respiratory diseases
      relative to those without (controls) were calculated, after adjustments were made
      for potential confounders. RESULTS: Chronic respiratory disease was associated
      with a higher prevalence of depressive disorders with an odds ratio of 1.58 (95%
      CI = 1.12-2.13) after adjustment was made for age, sex, cigarette smoking,
      alcohol drinking and history of cardiovascular diseases when compared with
      controls. For those subjects with self report of chronic respiratory disease and
      who screened positive for depression (n = 44), none were on antidepressants.
      Among subjects who screened positive for depression without self-report of
      chronic respiratory disease (n = 328), only 2.74% (n = 9) were on
      antidepressants. CONCLUSIONS: We conclude that chronic respiratory disease is
      independently associated with depression in Chinese elderly. Moreover, depression
      in the elderly is under-treated in those with and without chronic respiratory
      disease. Clinicians, especially primary care physicians in the community, should
      be more aware of increased prevalence of depression in patients with chronic
      respiratory disease.

PMID- 16440405
TI  - The Organic Brain Syndrome (OBS) scale: a systematic review.
AB  - BACKGROUND/OBJECTIVE: The Organic Brain Syndrome (OBS) Scale was developed to
      determine elderly patients' disturbances of awareness and orientation as to time,
      place and own identity, and assessment of various emotional and behavioural
      symptoms appearing in delirium, dementia and other organic mental diseases. The
      aim of the study was to examine the OBS Scale, using the eight criteria and
      guidelines formulated by the Scientific Advisory Committee of the Medical
      Outcomes Trust (SAC), and to investigate its relevance and suitability for use in
      various clinical settings. METHOD: Systematic search and analysis of papers (30)
      on the OBS Scale were carried out using the criteria suggested by the SAC.
      RESULTS: The OBS Scale in many aspects satisfies the requirements suggested by
      the SAC: conceptual and measurement model, reliability, validity, responsiveness,
      interpretability, respondent and administrative burden, alternative forms of
      administration, and cultural and language adaptations, but there is a need for
      additional evaluation, especially with regard to different forms of reliability,
      and the translation and adaptation to other languages. CONCLUSIONS: The OBS Scale
      is a sensitive scale which is clinically useful for the description and long-term
      follow-up of patients showing symptoms of acute confusional state and dementia.
      Although the OBS Scale has been used in several clinical studies there is need
      for further evaluation.

PMID- 16440406
TI  - Using duration of memory loss to improve differentiation of mild cognitive
      impairment from normal cognition.

PMID- 16440408
TI  - Changing face of irritable bowel syndrome.
AB  - Recent years have witnessed tremendous progress in our understanding of irritable
      bowel syndrome (IBS). It is evident that this is a truly global disease
      associated with significant symptoms and impairments in personal and social
      functioning for afflicted individuals. Advances in our understanding of gut flora
      mucosal interactions, the enteric nervous system and the brain-gut axis have led
      to substantial progress in the pathogenesis of symptoms in IBS and have provided
      some hints towards the basic etiology of this disorder, in some subpopulations,
      at the very least. We look forward to a time when therapy will be addressed to
      pathophysiology and perhaps, even to primary etiology. In the meantime, a model
      based on a primary role for intestinal inflammation serves to integrate the
      various strands, which contribute to the presentation of IBS.

PMID- 16440409
TI  - Helicobacter pylori virulence factors in duodenal ulceration: A primary cause or
      a secondary infection causing chronicity.
AB  - Reports from countries with a high prevalence of Helicobacter pylori (H pylori)
      infection do not show a proportionately high prevalence of duodenal ulceration,
      suggesting the possibility that H pylori cannot be a primary cause of duodenal
      ulceration. It has been mooted that this discrepancy might be explained by
      variations in the prevalence of virulence factors in different populations. The
      aim of this paper is to determine whether the published literature gives support
      to this possibility. The relevant literature was reviewed and analyzed separately
      for countries with a high and low prevalence of H pylori infection and virulence
      factors. Although virulent strains of H pylori were significantly more often
      present in patients with duodenal ulcer than without the disease in countries
      with a low prevalence of H pylori infection in the population, there was no
      difference in the prevalence of virulence factors between duodenal ulcer, non -
      ulcer dyspepsia or normal subjects in many countries, where the prevalence of
      both H pylori infection and of virulence factors was high. In these countries,
      the presence of virulence factors was not predictive the clinical outcome. To
      explain the association between virulence factors and duodenal ulcer in countries
      where H pylori prevalence is low, only two papers were found that give little
      support to the usual model proposed, namely that organisms with the virulence
      factors are more likely than those without them to initiate a duodenal ulcer. We
      offer an alternative hypothesis that suggests virulence factors are more likely
      to interfere with the healing of a previously produced ulcer. The presence of
      virulence factors only correlates with the prevalence of duodenal ulcer in
      countries where the prevalence of H pylori is low. There is very little evidence
      that virulence factors initiate duodenal ulceration, but they may be related to
      failure of the ulcer to heal.

PMID- 16440410
TI  - Causal role of Helicobacter pylori infection and eradication therapy in gastric
      carcinogenesis.
AB  - Many epidemiological reports indicate that Helicobacter pylori (H pylori)
      infection plays an important role in gastric carcinogenesis. Several genetic and
      epigenetic alterations contribute to the initiation, promotion, and progression
      of the cancer cells in a multi-step manner. H pylori is known to induce chronic
      inflammation in the gastric mucosa. Its products, including superoxides,
      participate in the DNA damage followed by initiation, and the inflammation
      derived cytokines and growth factors contribute to the promotion of gastric
      carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the
      therapy diminishes the levels not only of inflammatory cell infiltration, but
      also atrophy/intestinal metaplasia in part. A randomized controlled trial
      revealed that the eradication therapy diminished the gastric cancer prevalence in
      cases without pre-cancerous conditions. In addition, recent epidemiological
      studies from Japanese groups demonstrated that the development of gastric cancer,
      especially of the intestinal type, was decreased by successful eradication
      therapy, although these were designed in a non-randomized manner. However, it
      should be mentioned that endoscopic detection is the only way to evaluate the
      degree of gastric carcinogenesis. We have reported that the endoscopic and
      histological morphologies could be modified by eradication therapy and it might
      contribute to the prevalence of gastric cancer development. Considering the
      biological nature of cancer cell proliferation, it is considered that a
      sufficiently long-term follow-up would be essential to discuss the anticancer
      effect of eradication therapy.

PMID- 16440411
TI  - Incidence and mortality of gastric cancer in China.
AB  - Gastric cancer is one of the most frequent cancers in the world; almost two
      thirds of gastric cancer cases and deaths occur in less developed regions. In
      China, based on two national mortality surveys conducted in 1970s and 1990s,
      there is an obvious clustering of geographical distribution of gastric cancer in
      the country, with the high mortality being mostly located in rural areas,
      especially in Gansu, Henan, Hebei, Shanxi and Shaanxi Provinces in the middle
      western part of China. Despite a slight increase from the 1970s to early 1990s,
      remarkable declines in gastric cancer mortality were noticed in almost the entire
      population during the last decade in China. These declines were largely due to
      the dramatic improvements in the social-economic environment, lifestyle,
      nutrition, education and health care system after economic reforms started two
      decades ago. Nevertheless, gastric cancer will remain a significant cancer burden
      currently and be one of the key issues in cancer prevention and control strategy
      in China. It was predicted that, in 2005, 0.3 million deaths and 0.4 million new
      cases from gastric cancer would rank the third most common cancer. The essential
      package of the prevention and control strategy for gastric cancer in China would
      focus on controlling Helicobacter pylori (H. pylori) infection, improving
      educational levels, advocating healthy diet and anti-tobacco campaign, searching
      for cost-effective early detection, diagnosis and treatment programs including
      approaches for curable management and palliative care.

PMID- 16440412
TI  - Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU
      5 cell line.
AB  - AIM: To investigate the relationship between the inhibited growth (cytotoxic
      activity) of berberine and apoptotic pathway with its molecular mechanism of
      action. METHODS: The in vitro cytotoxic techniques were complemented by cell
      cycle analysis and determination of sub-G1 for apoptosis in human gastric
      carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub-G1 group
      (apoptosis) were examined and determined by the flow cytometric methods. The
      associated proteins for cell cycle arrest and apoptosis were examined by Western
      blotting. RESULTS: For SNU-5 cell line, the IC50 was found to be 48 micromol/L of
      berberine. In SNU-5 cells treated with 25-200 micromol/L berberine, G2/M cell
      cycle arrest was observed which was associated with a marked increment of the
      expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration
      dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were
      detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle
      measurement was proved in 25-200 micromol/L berberine-treated cells by monitoring
      the apoptotic pathway. Apoptosis was identified by sub-G0 cell population, and
      upregulation of Bax, downregulation of Bcl-2, release of Ca2+, decreased the
      mitochondrial membrane potential and then led to the release of mitochondrial
      cytochrome C into the cytoplasm and caused the activation of caspase-3, and
      finally led to the occurrence of apoptosis. CONCLUSION: Berberine induces p53
      expression and leads to the decrease of the mitochondrial membrane potential,
      Cytochrome C release and activation of caspase-3 for the induction of apoptosis.

PMID- 16440413
TI  - Inhibitory effect of Polo-like kinase 1 depletion on mitosis and apoptosis of
      gastric cancer cells.
AB  - AIM: Polo-like kinase 1 (PLK1) serine/threonine kinase plays a vital role in
      multiple phases of mitosis in gastric cancer cells. To investigate the effect of
      PLK1 depletion on mitosis and apoptosis of gastric cancer cells. METHODS: PLK1
      expression was blocked by small RNA interference(siRNA). The expression levels of
      PLK1, cdc2, cyclin B and caspase 3 were detected by Western blotting. Then, PLK1
      depletion, cdc2 activity, cell proliferation, cell cycle phase distribution,
      mitotic spindle structure, and the rate of apoptosis of the PLK1 knockdown cells
      were observed. RESULTS: PLK1 gene knockdown was associated with increased cyclin
      B expression, increased cdc2 activity (but not with the expression levels),
      accumulation of gastric cancer cells at G2/M, improper mitotic spindle formation,
      delayed chromosome separation and delayed or arrested cytokinesis. Moreover, PLK1
      depletion in gastric cancer cells was associated with decreased proliferation,
      attenuated pro-caspase 3 levels and increased apoptosis. CONCLUSION: Blockage of
      PLK1 expression may lead to decreased mitosis or even apoptosis in gastric cancer
      cells, indicating that PLK1 may be a valuable therapeutic target for gastric
      cancer.

PMID- 16440414
TI  - CD44v6 in peripheral blood and bone marrow of patients with gastric cancer as
      micro-metastasis.
AB  - AIM: To detect the expression of CD44 correlated with the ability of micro
      metastasis in peripheral blood and bone marrow of patients with gastric cancer
      and to deduce its clinical significance. METHODS: Preoperative peripheral blood
      and bone marrow specimens from 46 patients with gastric cancer and 6 controls
      were studied by semi-quantitative RT-PCR amplification of CD44v6mRNA.
      Preoperative and postoperative peripheral blood specimens from 40 patients with
      gastric cancer and 14 controls were studied by quantitative RT-PCR amplification
      of CD44v6mRNA in the corresponding period. RESULTS: Semi-quantitative RT-PCR
      amplification showed that CD44v6mRNA expression of peripheral blood and bone
      marrow was positive in 39 (84.8%) and 40 (86.9%) of 46 patients with gastric
      cancer, respectively. In peripheral blood, CD44v6mRNA expression was positive for
      diffuse type in 30 (93.8%) of 32 patients and for intestinal type in 9 (64.3%) of
      14 patients. On the other hand, in bone marrow, CD44v6mRNA expression was
      positive for diffuse type in 31 (96.9%) of 32 patients and for intestinal type in
      10 (71.4%) of 14 patients. There was a significant difference between the diffuse
      type and intestinal type. Quantitative RT-PCR amplification demonstrated that
      CD44v6mRNA was not expressed in the peripheral blood of controls and CD44v6mRNA
      expression was positive for preoperative peripheral blood in 40 patients with
      gastric cancer, the expression levels being from 4.9 x 10(8) - 3.2 x 10(11)
      copies/g RNA. The average expression level of CD44v6mRNA in peripheral blood was
      3.9 x 10(10) copies/g RNA. The expression levels of CD44v6mRNA in peripheral
      blood in gastric cancer patients after curative operation increased from 5.5 x
      10(6) to 7.6 x 10(9) copies/g RNA and the average level was 2.4 x 10(8) copies/g
      RNA (Figure 3B) (P = 0.00496). After curative operation, the expression level
      decreased markedly. CONCLUSION: Semi-quantitative and quantitative RT-PCR
      amplification for CD44v6mRNA is a sensitive and specific method for the detection
      of micro-metastasis in peripheral blood and bone marrow, which might be used as
      an indicator of tumor burden and therapeutic effect.

PMID- 16440415
TI  - Usefulness of endoscopic ultrasonography in preoperative TNM staging of gastric
      cancer.
AB  - AIM: To evaluate the value of endoscopic ultrasonography (EUS) in the
      preoperative TNM staging of gastric cancer. METHODS: Forty-one patients with
      gastric cancer (12 early stage and 29 advanced stage) proved by
      esophagogastroduodenoscopy and biopsies preoperatively evaluated with EUS
      according to TNM (1997) classification of International Union Contrele Cancer
      (UICC). Pentax EG-3630U/Hitachi EUB-525 echo endoscope with real-time ultrasound
      imaging linear scanning transducers (7.5 and 5.0 MHz) and Doppler information was
      used in the current study. EUS staging procedures for tumor depth of invasion (T
      stage) were performed according to the widely accepted five-layer structure of
      the gastric wall. All patients underwent surgery. Diagnostic accuracy of EUS for
      TNM staging of gastric cancer was determined by comparing preoperative EUS with
      subsequent postoperative histopathologic findings. RESULTS: The overall
      diagnostic accuracy of EUS in preoperative determination of cancer depth of
      invasion was 68.3% (41/28) and 83.3% (12/10), 60% (20/12), 100% (5/5), 25% (4/1)
      for T1, T2, T3, and T4, respectively. The rates for overstaging and understaging
      were 24.4% (41/10), and 7.3% (41/3), respectively. EUS tended to overstage T
      criteria, and main reasons for overstaging were thickening of the gastric wall
      due to perifocal inflammatory change, and absence of serosal layer in certain
      areas of the stomach. The diagnostic accuracy of metastatic lymph node
      involvement or N staging of EUS was 100% (17/17) for N0 and 41.7% (24/10) for N+,
      respectively, and 66% (41/27) overall. Misdiagnosing of the metastatic lymph
      nodes was related to the difficulty of distinguishing inflammatory lymph nodes
      from malignant lymph nodes, which imitate similar echo features. Predominant
      location and distribution of tumors in the stomach were in the antrum (20
      patients), and the lesser curvature (17 patients), respectively. Three cases were
      found as surgically unresectable (T4 N+), and included as being correctly
      diagnosed by EUS. CONCLUSION: EUS is a useful diagnostic method for preoperative
      staging of gastric cancer for T and N criteria. However, EUS evaluation of
      malignant lymph nodes is still unsatisfactory.

PMID- 16440416
TI  - Hepatocellular carcinoma in extremely elderly patients: an analysis of clinical
      characteristics, prognosis and patient survival.
AB  - AIM: To identify the clinical and prognostic features of patients with
      hepatocellular carcinoma (HCC) aged 80 years or more. METHODS: A total of 1310
      patients with HCC were included in this study. Ninety-one patients aged 80 years
      or more at the time of diagnosis of HCC were defined as the extremely elderly
      group. Two hundred and thirty-four patients aged > or = 50 years but less than 60
      years were regarded as the non-elderly group. RESULTS: The sex ratio (male to
      female) was significantly lower in the extremely elderly group (0.90:1) than in
      the non-elderly group (3.9:1, P < 0.001). The positive rate for HBsAg was
      significantly lower in the extremely elderly group and the proportion of patients
      negative for HBsAg and HCVAb obviously increased in the extremely elderly group
      (P < 0.001). There were no significant differences in the following parameters:
      diameter and number of tumors, Child-Pugh grading, tumor staging, presence of
      portal thrombosis or ascites, and positive rate for HCVAb. Extremely elderly
      patients did not often receive surgical treatment (P < 0.001) and they were more
      likely to receive conservative treatment (P < 0.01). There were no significant
      differences in survival curves based on the Kaplan-Meier methods in comparison
      with the overall patients between the two groups. However, the survival curves
      were significantly worse in the extremely elderly patients with stage I/II, stage
      I/II and Child-Pugh grade A cirrhosis in comparison with the non-elderly group.
      The causes of death did not differ among the patients, and most cases died of
      liver-related diseases even in the extremely elderly patients. CONCLUSION: In the
      patients with good liver functions and good performance status, aggressive
      treatment for HCC might improve the survival rate, even in the extremely elderly
      patients.

PMID- 16440417
TI  - Clinical significance of subcellular localization of KL-6 mucin in primary
      colorectal adenocarcinoma and metastatic tissues.
AB  - AIM: To assess subcellular localization of KL-6 mucin and its clinicopathological
      significance in colorectal carcinoma as well as metastatic lymph node and liver
      tissues. METHODS: Colorectal carcinoma tissues as well as metastatic lymph node
      and liver tissues were collected from 82 patients who underwent colorectomy or
      hepatectomy. Tissues were subjected to immunohistochemical analysis using KL-6
      antibody. RESULTS: Of the 82 colorectal carcinoma patients, 6 showed no staining,
      29 showed positive staining only in the apical membrane, and 47 showed positive
      staining in the circumferential membrane and/or cytoplasm. Positive staining was
      not observed in non-cancerous colorectal epithelial cells surrounding the tumor
      tissues. The five-year survival rate was significantly lower in cases showing
      positive staining in the circumferential membrane and/or cytoplasm (63.0%) than
      those showing positive staining only in the apical membrane (85.7%) and those
      showing no staining (100%). Statistical analysis between clinicopathological
      factors and subcellular localization of KL-6 mucin showed that KL-6 localization
      in the circumferential membrane and/or cytoplasm was significantly associated
      with the presence of venous invasion (P = 0.0003), lymphatic invasion (P<0.0001),
      lymph node metastasis (P<0.0001), liver metastasis (P = 0.058), and advanced
      histological stage (P<0.0001). Positive staining was observed in all metastatic
      lesions tested as well as in the primary colorectal carcinoma tissues.
      CONCLUSION: The subcellular staining pattern of KL-6 in colorectal adenocarcinoma
      may be an important indicator for unfavorable behaviors such as lymph node and
      liver metastasis, as well as for the prognosis of patients.

PMID- 16440418
TI  - Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer
      cells.
AB  - AIM: To examine whether antithrombin (AT) could prevent hepatic
      ischemia/reperfusion (I/R)-induced hepatic metastasis by inhibiting tumor
      necrosis factor (TNF)-alpha-induced expression of E-selectin in rats. METHODS:
      Hepatic I/R was induced in rats and mice by clamping the left branches of the
      portal vein and the hepatic artery. Cancer cells were injected intrasplenically.
      The number of metastatic nodules was counted on day 7 after I/R. TNF-alpha and E
      selectin mRNA in hepatic tissue, serum fibrinogen degradation products and
      hepatic tissue levels of 6-keto-PGF(1alpha), a stable metabolite of PGI2, were
      measured. RESULTS: AT inhibited increases in hepatic metastasis of tumor cells
      and hepatic tissue mRNA levels of TNF-alpha and E-selectin in animals subjected
      to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these
      changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities.
      I/R-induced increases of hepatic tissue levels of 6-keto-PGF(1alpha) were
      significantly enhanced by AT. Pretreatment with indomethacin completely reversed
      the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed
      effects similar to those of AT in this model. Hepatic metastasis in congenital AT
      deficient mice subjected to hepatic I/R was significantly increased compared to
      that observed in wild-type mice. Administration of AT significantly reduced the
      number of hepatic metastases in congenital AT-deficient mice. CONCLUSION: AT
      might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting
      TNF-alpha-induced expression of E-selectin through an increase in the endothelial
      production of PGI2. These findings also raise the possibility that AT might
      prevent hepatic metastasis of tumor cells if administered during the resection of
      liver tumors.

PMID- 16440419
TI  - Discrepancies between primary physician practice and treatment guidelines for
      Helicobacter pylori infection in Korea.
AB  - AIM: To evaluate the attitude of primary care physicians in the diagnosis and
      treatment of Helicobacter pylori (H. pylori) infection. METHODS: Primary care
      physicians in the Seoul metropolitan area answered self-administered
      questionnaire from January to March 2003. RESULTS: One hundred and eight doctors
      responded to the questionnaire. The most frequent reasons for testing H. pylori
      infection were gastric and duodenal ulcers (93.5% and 88.9%, respectively). For
      patients with H. pylori positive dyspepsia, 28.7% of doctors always tried to
      eradicate the worm and 34.4% treated selectively. A large proportion (28.7%) of
      primary care physicians treated H. pylori on a patient's request basis. Only 9.3%
      of primary care physicians always conducted follow-up testing after treating H.
      pylori infection. When H. pylori was not cleared by the first treatment, 40.7% of
      doctors reused the same regimen, 16.7% changed to another triple regimen and 25%
      to a quadruple regimen. CONCLUSION: It has been well documented that the issuance
      of guidelines alone has little impact on practice. Communication between primary
      care physicians and gastroenterologists in the form of continuous medical
      education is required.

PMID- 16440420
TI  - Gallbladder bile composition in patients with Crohn 's disease.
AB  - AIM: To further elucidate the pathogenesis and mechanisms of the high risk of
      gallstone formation in Crohn's disease. METHODS: Gallbladder bile was obtained
      from patients with Crohn's disease who were admitted for elective surgery (17
      with ileal/ileocolonic disease and 7 with Crohn's colitis). Fourteen gallstone
      patients served as controls. Duodenal bile was obtained from ten healthy subjects
      before and after the treatment with ursodeoxycholic acid. Bile was analyzed for
      biliary lipids, bile acids, bilirubin, crystals, and crystal detection time
      (CDT). Cholesterol saturation index was calculated. RESULTS: The biliary
      concentration of bilirubin was about 50% higher in patients with Crohn's disease
      than in patients with cholesterol gallstones. Ten of the patients with Crohn's
      disease involving ileum and three of those with Crohn's colitis had cholesterol
      saturated bile. Four patients with ileal disease and one of those with colonic
      disease displayed cholesterol crystals in their bile. About 1/3 of the patients
      with Crohn's disease had a short CDT. Treatment of healthy subjects with
      ursodeoxycholic acid did not increase the concentration of bilirubin in duodenal
      bile. Several patients with Crohn's disease, with or without ileal
      resection/disease had gallbladder bile supersaturated with cholesterol and short
      CDT and contained cholesterol crystals. The biliary concentration of bilirubin
      was also increased in patients with Crohn's colitis probably not due to bile acid
      malabsorption. CONCLUSION: Several factors may be of importance for the high risk
      of developing gallstones of both cholesterol and pigment types in patients with
      Crohn's disease.

PMID- 16440421
TI  - Crohn's disease in Stockholm County during 1990-2001: an epidemiological update.
AB  - AIM: To further assess of the incidence and localization of Crohn's disease (CD)
      in a well-defined population during the 1990s and to evaluate the prevalence of
      CD on the 1st of January 2002. METHODS: In a retrospective population based
      study, all 16-90 years old citizens of Stockholm County diagnosed as having CD
      according to Lennard Jones' criteria between 1990 and 2001 were included. Case
      identification was made by using computerized inpatient and outpatient registers.
      Moreover private gastroenterologists were asked for possible cases. The extent of
      the disease and the frequency of anorectal fistulae were determined as were the
      ages at diagnosis. Further, the prevalence of CD on the 1(st) of January 2002 was
      assessed. RESULTS: All the 1 389 patients, 689 men and 700 women, fulfilled the
      criteria for CD. The mean incidence rate for the whole period was 8.3 per 10(5)
      (95%CI 7.9 -8.8). There was no difference between the genders. The mean annual
      incidence of the whole study period for colorectal disease and ileocecal disease,
      was 4.4 (95%CI 4.0-4.7) and 2.4 (95%CI 2.1-2.6) per 10(5), respectively. Perianal
      disease occurred in 13.7% (95%CI 11.9-15.7 %) of the patients. The prevalence of
      CD was 213 per 100,000 inhabitants. CONCLUSION: The incidence of CD has markedly
      increased during the last decade in Stockholm County and 0.2% of the population
      suffers from CD. The increase is attributed to a further increase of colorectal
      disease, while the incidence of ileocecal disease has remained stable.

PMID- 16440422
TI  - Proton pump inhibitor treatment of patients with gastroesophageal reflux-related
      chronic cough: a comparison between two different daily doses of lansoprazole.
AB  - AIM: To compare two different daily doses of lansoprazole given for 12 weeks and
      to assess the role of gastrointestinal (GI) investigations as criteria for
      selecting patients. METHODS: Out of 45 patients referred for unexplained chronic
      persistent cough, 36 had at least one of the GI investigations (endoscopy, 24-h
      esophageal pH-metry and a 4-week trial of proton pump inhibitor (PPI) therapy)
      positive and were randomly assigned to receive either 30 mg lansoprazole o.d. or
      30 mg lansoprazole b.i.d. for 12 weeks. Symptoms were evaluated at baseline
      (visit 1) after the PPI test (visit 2) and after the 12-week lansoprazole
      treatment period (visit 3). RESULTS: Thirty-five patients completed the study
      protocol. Twenty-one patients (60.0%) reported complete relief from their cough
      with no difference between the two treatment groups (58.8% and 61.1% had no cough
      in 30 mg lansoprazole and 60 mg lansoprazole groups, respectively). More than 80%
      of the patients who had complete relief from their cough at the end of the
      treatment showed a positive response to the PPI test. CONCLUSION: Twelve weeks of
      lansoprazole treatment even at a standard daily dose, is effective in patients
      with chronic persistent cough. A positive response to an initial PPI test seems
      to be the best criterion for selecting patients who respond to therapy.

PMID- 16440423
TI  - Benefits of early postoperative jejunal feeding in patients undergoing
      duodenohemipancreatectomy.
AB  - AIM: To study whether early postoperative enteral nutrition reduces the incidence
      of complications and/or improves nutritional status following
      duodenohemipancreatectomy (DHP). METHODS: We studied 39 patients who underwent
      DHP for a peri-ampullary mass. Twenty-three patients received total parental
      nutrition and then started to have an oral intake of nutrition between
      postoperative day (POD) 7 and 14 [late postoperative enteral nutrition (LPEN)
      group]. Sixteen patients started to have enteral feeding through a jejunostomy
      catheter the day after the operation [early postoperative enteral nutrition
      (EPEN) group]. The incidence of complications and laboratory data at the early
      postoperative stage were studied in comparison between LPEN and EPEN groups.
      RESULTS: Serum levels of albumin and total protein in the EPEN group were
      significantly higher than those in the LPEN group. The loss of body mass index
      was significantly suppressed in the EPEN group as compared to the LPEN group. The
      lymphocyte count decreased immediately after the operation was restored
      significantly faster in the EPEN group than in the LPEN group. The EPEN group
      showed significantly fewer incidences of postoperative pancreatic fistulas, as
      well as a significantly shorter length of hospitalization than the LPEN group.
      There were no significant differences in the incidences of other postoperative
      complications between the two groups, such as delayed gastric emptying, surgical
      site infection, cholangitis, and small bowel obstruction. CONCLUSION: EPEN is a
      safe and beneficial opportunity for patients who have undergone DHP for a peri
      ampullary mass.

PMID- 16440424
TI  - L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine
      carcinoma.
AB  - AIM: To determine the expression of L1 in pancreatic neuroendocrine tumor and to
      correlate it with WHO classification of this tumor. METHODS: We retrospectively
      analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by
      immunohistochemistry on paraffin sections of primary tumors or metastases.
      Staining was performed by peroxidase technique with monoclonal antibody UJ127.11
      against human L1. All tumors were classified according to WHO classification as
      well-differentiated neuroendocrine tumors and carcinomas or poorly-differentiated
      neuroendocrine carcinomas. RESULTS: L1 was detected in 5 (7.9%) of 63 pancreatic
      neuroendocrine tumors. Four (44.4%) of 9 poorly-differentiated carcinomas
      expressed L1. In contrast, only 1 (1.9%) of 54 well-differentiated tumors or
      carcinomas was positive for L1. No expression was found in Langerhans islet cells
      of normal pancreatic tissue. Cross table analysis showed a significant
      association between L1 expression and classification of neuroendocrine tumors of
      the pancreas (P<0.01). CONCLUSION: L1 is specifically expressed in poorly
      differentiated pancreatic neuroendocrine carcinomas that are known to have the
      worst prognosis. L1 might be a marker for risk prediction of patients diagnosed
      with pancreatic neuroendocrine carcinomas.

PMID- 16440425
TI  - Risk factors for immediate post-operative fatal recurrence after curative
      resection of hepatocellular carcinoma.
AB  - AIM: To investigate the clinicopathological risk factors for immediate post
      operative fatal recurrence of hepatocellular carcinoma (HCC), which may have
      practical implication and contribute to establishing high risk patients for pre-
      or post-operative preventive measures against HCC recurrence. METHODS: From June
      1994 to May 2004, 269 patients who received curative resection for HCC were
      reviewed. Of these patients, those who demonstrated diffuse intra-hepatic or
      multiple systemic recurrent lesions within 6 mo after surgery were investigated
      (fatal recurrence group). The remaining patients were designated as the control
      group, and the two groups were compared for clinicopathologic risk factors.
      RESULTS: Among the 269 patients reviewed, 30 patients were enrolled in the fatal
      recurrence group. Among the latter, 20 patients showed diffuse intra-hepatic
      recurrence type and 10 showed multiple systemic recurrence type. Multivariate
      analysis between the fatal recurrence group and control group showed that pre
      operative serum alpha-fetoprotein (AFP) level was greater than 1,000 microg/L (P
      = 0.02; odds ratio = 2.98), tumor size greater than 6.5 cm (P = 0.03; OR = 2.98),
      and presence of microvascular invasion (P = 0.01; OR = 4.89) were the risk
      factors in the fatal recurrence group. The 48.1% of the patients who had all the
      three risk factors and the 22% of those who had two risk factors experienced
      fatal recurrence within 6 mo after surgery. CONCLUSION: Three distinct risk
      factors for immediate post-operative fatal recurrence of HCC after curative
      resection are pre-operative serum AFP level > 1,000 microg/L, tumor size > 6.5
      cm, and microvascular invasion. The high risk patients with two or more risk
      factors should be the candidates for various adjuvant clinical trials.

PMID- 16440426
TI  - Detection of gelatinase B activity in serum of gastric cancer patients.
AB  - AIM: To determine the proteolytic activity and expression of gelatinase B in
      serum of gastric cancer patients and their correlation with the stage of the
      tumor. METHODS: Sera from 23 patients who underwent surgery for primary gastric
      cancer as the experimental group and from 11 as the control group were used to
      determine the proteolytic activity and its inhibition by EDTA and 1,10
      phenanthroline. Gelatinase B activity was detected by SDS polyacrylamide gel
      electrophoresis (SDS-PAGE) and SDS-PAGE zymography. RESULTS: Proteolytic enzyme
      activity was increased in gastric cancer patients when compared to the control
      group (P < 0.05). The proteinases were determined to be metalloproteinases upon
      inhibition test with specific metalloproteinase inhibitors 1,10-phenanthroline (P
      < 0.05) and EDTA (P < 0.01). SDS-PAGE and SDS-PAGE zymography revealed gelatinase
      B (proMMP-9) activity and its molecular mass of 92 ku. CONCLUSION: Proteinase
      activity is overexpressed in serum of gastric cancer patients. Gelatinase B in
      serum plays an important role in the progression of gastric cancer. ProMMP-9 can
      be used as a marker for invasiveness of gastric cancer.

PMID- 16440427
TI  - Changes of plasma fasting carnitine ester profile in patients with ulcerative
      colitis.
AB  - AIM: To determine the plasma carnitine ester profile in adult patients with
      ulcerative culitis (UC) and compared with healthy control subjects. METHOD: Using
      ESI triple quadrupole tandem mass spectrometry, the carnitine ester profile was
      measured in 44 patients with UC and 44 age- and sex-matched healthy controls.
      RESULTS: There was no significant difference in the fasting free carnitine level
      between the patients with UC and the healthy controls. The fasting propionyl-
      (0.331 +/- 0.019 vs 0.392 +/- 0.017 micromol/L), butyryl- (0.219 +/- 0.014 vs
      0.265 +/- 0.012), and isovalerylcarnitine (0.111 +/- 0.008 vs 0.134 +/- 0.008)
      levels were decreased in the UC patients. By contrast, the level of octanoyl
      (0.147 +/- 0.009 vs 0.114 +/- 0.008), decanoyl- (0.180 +/- 0.012 vs 0.137 +/-
      0.008), myristoyl- (0.048 +/- 0.003 vs 0.039 +/- 0.003), palmitoyl- (0.128 +/-
      0.006 vs 0.109 +/- 0.004), palmitoleyl- (0.042 +/- 0.003 vs 0.031 +/- 0.002) and
      oleylcarnitine (0.183 +/- 0.007 vs 0.163 +/- 0.007; P < 0.05 in all comparisons)
      were increased in the patients with UC. CONCLUSION: Our data suggest selective
      involvement of the carnitine esters in UC patients, probably due to their altered
      metabolism.

PMID- 16440428
TI  - Effect of percutaneous endoscopic gastrostomy on gastro-esophageal reflux in
      mechanically-ventilated patients.
AB  - AIM: To investigate the effect of percutaneous endoscopic gastrostomy (PEG) on
      gastroesophageal reflux (GER) in mechanically-ventilated patients. METHODS: In a
      prospective, randomized, controlled study 36 patients with recurrent or
      persistent ventilator-associated pneumonia (VAP) and GER > 6% were divided into
      PEG group (n = 16) or non-PEG group (n = 20). Another 11 ventilated patients
      without reflux (GER < 3%) served as control group. Esophageal pH-metry was
      performed by the "pull through" method at baseline, 2 and 7 d after PEG. Patients
      were strictly followed up for semi-recumbent position and control of gastric
      nutrient residue. RESULTS: A significant decrease of median (range) reflux was
      observed in PEG group from 7.8 (6.2 - 15.6) at baseline to 2.7 (0 - 10.4) on d 7
      post-gastrostomy (P < 0.01), while the reflux increased from 9 (6.2 - 22) to 10.8
      (6.3 - 36.6) (P < 0.01) in non-PEG group. A significant correlation between GER
      (%) and the stay of nasogastric tube was detected (r = 0.56, P < 0.01).
      CONCLUSION: Gastrostomy when combined with semi-recumbent position and absence of
      nutrient gastric residue reduces the gastroesophageal reflux in ventilated
      patients.

PMID- 16440429
TI  - Self-expandable metallic stents for malignant biliary obstruction: efficacy on
      proximal and distal tumors.
AB  - AIM: To compare the efficacy of self-expandable metallic stents (EMS) in the
      treatment of distal and proximal stricture of malignant biliary tumors. METHODS:
      From March 1995 to June 2004, 61 patients (40 males, 21 females) with malignant
      biliary obstruction who received self-expandable metallic stent implantation were
      reviewed retrospectively. The stents were inserted by an endoscopic or
      percutaneous transhepatic method. We tried to place two stents in the biliary
      system in T or Y configuration in cases of hilar tumors with bilateral hepatic
      duct obstruction. The end points of the study were stent occlusion or patient
      death. RESULTS: The mean time of stent patency was 421 +/- 67 d in the group of
      proximal stricture (group I) and 168 +/- 18 d in the group of distal stricture
      (group II). The difference was significant in borderline between the two groups
      (P = 0.0567). The mean survival time was 574 +/- 76 d in group I and 182 +/- 25 d
      in group II. There was a significant difference between the two groups (P =
      0.0005). CONCLUSION: EMS implantation is a feasible, palliative method for
      unresectable malignant biliary obstruction. The clinical efficacy of EMS in
      patients with proximal hilar tumors is better than that in patients with distal
      tumors.

PMID- 16440430
TI  - Evaluation of contrast-enhanced computed tomographic colonography in detection of
      local recurrent colorectal cancer.
AB  - AIM: To evaluate the diagnostic accuracy, sensitivity, specificity of contrast
      enhanced computed tomographic colonography in detecting local recurrence of
      colorectal cancer. METHODS: From January 2000 to December 2004, 434 patients
      after potentially curative resection for invasive colorectal cancer were followed
      up for a period ranging from 20 to 55 mo. Eighty of the four hundred and thirty
      four patients showing strong clinical evidence for recurring colorectal cancer
      during the last follow-up were enrolled in this study. Each patient underwent
      contrast-enhanced computed tomographic colonography and colonoscopy on the same
      day. Any lesions, biopsies, identified during the colonoscopic examination,
      immediate complications and the duration of the procedure were recorded. The
      results of contrast-enhanced computed tomographic colonography were evaluated by
      comparing to those of colonoscopy, surgical finding, and clinical follow-up.
      RESULTS: Contrast-enhanced computed tomographic colonography had a sensitivity of
      100%, a specificity of 83% and an overall accuracy of 94% in detecting local
      recurrent colorectal cancer. CONCLUSION: Conventional colonoscopy and contrast
      enhanced tomographic colonography can complement each other in detecting local
      recurrence of colorectal cancer.

PMID- 16440431
TI  - Influence of HBcAg in liver cell plasma on expression of transforming growth
      factor-beta 1 in liver tissue of low-grade chronic hepatitis B patients.
AB  - AIM: To study the influence of HBcAg on the expression of transforming growth
      factor-beta 1 (TGF-beta1) in liver tissue of low-grade chronic hepatitis B (CHB)
      patients. METHODS: The expression of TGF-beta1 and HBcAg in liver samples from 93
      low-grade CHB patients was detected by immunohistochemistry and valuated by semi
      quantitative scoring. RESULTS: In the 93 low-grade CHB patients, HBcAg was
      expressed in cell plasma but not in the liver tissue. There was no significant
      difference between the two groups. CONCLUSION: The expression of TGF-beta1 is not
      related with HBcAg expressed as plasma type in the tissues of low-grade CHB
      patients.

PMID- 16440432
TI  - Clinical application of plasma shock wave lithotripsy in treating impacted stones
      in the bile duct system.
AB  - AIM: To verify the safety and efficacy of plasma shock wave lithotripsy (PSWL) in
      fragmenting impacted stones in the bile duct system. METHODS: From September 1988
      to April 2005, 67 patients (26 men and 41 women) with impacted stones underwent
      various biliary operations with tube (or T-tube) drainage. Remnant and impacted
      stones in the bile duct system found by cholangiography after the operation were
      fragmented by PSWL and choledochofiberscopy. A total of 201 impacted stones were
      fragmented by PSWL setting the voltage at 2.5-3.5 kV, and the energy output at 2
      3 J for each pulse of PSWL. Then the fragmented stones were extracted by
      choledochofiberscopy. The safety and efficacy of PSWL were observed during and
      after the procedure. RESULTS: One hundred and ninety-nine of 201 impacted stones
      (99.0%) in the bile duct system were successfully fragmented using PSWL and
      extracted by choledochofiberscopy. The stone clearance rate for patients was 97%
      (65/67). Ten patients felt mild pain in the right upper quadrant of the abdomen,
      and could tolerate it well. Eleven patients had a small amount of bleeding from
      the mucosa of the bile duct. The bleeding was transient and stopped spontaneously
      within 2 min of normal saline irrigation. There were no significant complications
      during and after the procedure. CONCLUSION: PSWL is a safe and effective method
      for fragmenting impacted stones in the bile duct system.

PMID- 16440433
TI  - Interventional therapy for acute hemorrhage in gastrointestinal tract.
AB  - AIM: To evaluate the diagnostic angiography and therapy for acute massive
      hemorrhage in gastrointestinal tract. METHODS: Twenty-five cases of acute
      hemorrhage in gastrointestinal tract admitted between April 2002 and September
      2004 were reviewed and analyzed by angiography and embolotherapy. RESULTS:
      Fifteen patients were men and ten patients were women. The Seldinger technique
      and method of coaxial duct were used to get access to the bleeding region. PVA
      particles, gelfoam, and coils were used for embolism. All bleeding sites could be
      confirmed and were successfully embolized. Hemostasis was achieved in all the
      patients without bleeding again. The cure rate was 100%. CONCLUSION:
      Interventional therapy can not only ascertain the bleeding site, but also stop
      the bleeding . The method is simple and the effect is certain.

PMID- 16440434
TI  - Effect of resveratrol on pancreatic oxygen free radicals in rats with severe
      acute pancreatitis.
AB  - AIM: To investigate the therapeutic effects of resveratrol (RESV) as a free
      radical scavenger on experimental severe acute pancreatitis (SAP). METHODS:
      Seventy-two male Sprague-Dawley rats were divided randomly into sham operation
      group, SAP group, and resveratrol-treated group. Pancreatitis was induced by
      intraductal administration of 0.1 mL/kg 4% sodium taurocholate. RESV was given
      intravenously at a dose of 20 mg/kg body weight. All animals were killed at 3, 6,
      12 h after induction of the model. Serum amylase, pancreatic superoxide dismutase
      (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) were determined.
      Pathologic changes of the pancreas were observed under optical microscope.
      RESULTS: The serum amylase, pancreatic MPO and the score of pathologic damage
      increased after the induction of pancreatitis, early (3, 6 h) SAP samples were
      characterized by decreased pancreatic SOD and increased pancreatic MDA.
      Resveratrol exhibited a protective effect against lipid peroxidation in cell
      membrane caused by oxygen free radicals in the early stage of SAP. This
      attenuation of the redox state impairment reduced cellular oxidative damage, as
      reflected by lower serum amylase, less severe pancreatic lesions, normal
      pancreatic MDA levels, as well as diminished neutrophil infiltration in pancreas.
      CONCLUSION: RESV may exert its therapeutic effect on SAP by lowering pancreatic
      oxidative free radicals and reducing pancreatic tissue infiltration of
      neutrophils.

PMID- 16440435
TI  - Known and probable risk factors for hepatitis C infection: a case series in north
      eastern Poland.
AB  - AIM: To describe the risk profile of patients in hospital with hepatitis C virus
      (HCV) infection in Poland. METHOD: Using a structured questionnaire, all patients
      with confirmed HCV infection were interviewed about the risk factors. RESULTS:
      Among the 250 patients studied, transfusion before 1993 was the primary risk
      factor in 26%, intravenous drug use setting in 9% and occupational exposure in
      health-care in 9%. Women were more likely to have a history of occupational
      exposure or transfusion before 1993 and less likely to undergo minor surgery.
      Known nosocomial risk factors (transfusion before 1993, dialysis) were
      responsible for 27% of infections, probable nosocomial factors (transfusions
      after 1992, minor surgery) for 14% and further 9% were occupationally acquired
      infections. CONCLUSION: A careful history investigation can identify a known or
      probable risk factor for HCV acquisition in 59% of patients with HCV infection.
      Preventive activities in Poland should focus on infection control measures in
      health-care setting.

PMID- 16440436
TI  - Sigmoidorectal intussusception of adenoma of sigmoid colon treated by
      laparoscopic anterior resection after sponge-on-the-stick-assisted manual
      reduction.
AB  - We present herein a case report of sigmoidorectal intussusception as an unusual
      case of sigmoid adenomatous polyp. The patient was a 56-year-old man who suffered
      from rectal bleeding for one day. He initially visited his general practitioner
      and was diagnosed as having an intraluminal mass of 15 cm from the anal verge.
      Several hours after admission to our coloproctology clinic, he suddenly presented
      with lower abdominal cramping pain with rectal bleeding during his bowel
      preparation using polyethylene glycol electrolyte solution. An emergency
      colonoscopy revealed that the invaginated colon with polypoid mass was protruded
      to the lower rectum. Gastrograffin enema showed that the invaginated bowel
      segment was 3 cm from the anal verge. CT scan showed the typical finding of
      intussusception. We performed laparoscopic anterior resection and anastomosis
      after the sponge-on-the-stick-assisted manual reduction. The permanent pathologic
      finding showed villotubular adenoma of the sigmoid colon.

PMID- 16440437
TI  - Spontaneous resolution of systemic sarcoidosis in a patient with chronic
      hepatitis C without interferon therapy.
AB  - A 39-year-old male patient complaining of bilateral hand joint arthralgia was
      evaluated and found to have chronic hepatitis C and systemic sarcoidosis
      involving lung, skin, liver, and spleen. Hepatic and cutaneous sarcoidoses were
      confirmed by the presence of numerous noncaseating granulomas on histological
      examination. Pulmonary and splenic involvements were diagnosed by imaging
      studies. Fifteen months later, the sarcoidotic lesions in lung, liver, and spleen
      were resolved by radiological studies and a liver biopsy showed no granuloma but
      moderate to severe inflammatory activity. systemic sarcoidosis is a rare
      comorbidity of chronic hepatitis C which may spontaneously resolve.

PMID- 16440438
TI  - Spontaneous chylous peritonitis mimicking acute appendicitis: a case report and
      review of literature.
AB  - Acute abdominal pain with signs and symptoms of peritonitis due to sudden
      extravasation of chyle into the peritoneal cavity is a rare condition that is
      often mistaken for other disease processes. The diagnosis is rarely suspected
      preoperatively. We report a case of spontaneous chylous peritonitis that
      presented with typical symptoms of acute appendicitis such as intermittent fever
      and epigastric pain radiating to the lower right abdominal quadrant before
      admission.

PMID- 16440440
TI  - Aspirin before bed.

PMID- 16440439
TI  - Percutaneous local therapies for hepatocellular carcinoma impair gastric
      function.

PMID- 16440441
TI  - Slow down for fish.

PMID- 16440442
TI  - Juice from the "jewel of winter" could be good for the heart.

PMID- 16440443
TI  - Cell phones and heart devices.

PMID- 16440444
TI  - Stem cell therapy: still more hope than help.

PMID- 16440445
TI  - Ask the doctor. My pulse is usually on the high side. Does that mean I have a
      problem with my heart?

PMID- 16440446
TI  - Historical Perspectives of the American Association for Thoracic Surgery: Carl
      Eggers (1879-1956).

PMID- 16440448
TI  - Abstracts of the joint meeting of the 2nd Latinamerican Symposium on Fetal
      Maternal Interaction and Placenta and the XIX Annual Meeting of the Chilean
      Society of Physiological Sciences, November 6-9, 2005, Santiago, Chile.

PMID- 16440447
TI  - Clathrin-independent endocytosis: new insights into caveolae and non-caveolar
      lipid raft carriers.
AB  - A number of recent studies have provided new insights into the complexity of the
      endocytic pathways originating at the plasma membrane of mammalian cells. Many of
      the molecules involved in clathrin coated pit internalization are now well
      understood but other pathways are less well defined. Caveolae appear to represent
      a low capacity but highly regulated pathway in a restricted set of tissues in
      vivo. A third pathway, which is both clathrin- and caveolae-independent, may
      constitute a specialized high capacity endocytic pathway for lipids and fluid.
      The relationship of this pathway, if any, to macropinocytosis or to the endocytic
      pathways of lower eukaryotes remains an interesting open question. Our
      understanding of the regulatory mechanisms and molecular components involved in
      this pathway are at a relatively primitive stage. In this review, we will
      consider some of the characteristics of different endocytic pathways in high and
      lower eukaryotes and consider some of the common themes in endocytosis. One theme
      which becomes apparent from comparison of these pathways is that apparently
      different pathways can share common molecular machinery and that pathways
      considered to be distinct actually represent similar basic pathways to which
      additional levels of regulatory complexity have been added.

PMID- 16440449
TI  - Cautious interpretation of findings (2/7/2005).

PMID- 16440450
TI  - Will interoperable HIT lead to a net gain or to a net loss for physicians?
      (2/23/2005).

PMID- 16440451
TI  - The need for real evidence in physician workforce decision making: a reply to Ed
      Salsberg (3/15/2005).

PMID- 16440452
TI  - Congressional delay puts 11 payment changes on hold.

PMID- 16440453
TI  - Standing tall. Exercises can help with the bad posture and osteoporosis that
      cause us to stoop and lose height as we get older.

PMID- 16440454
TI  - Medicare Part D: decision, decisions, decisions. Medicare prescription drug
      coverage should save many people some money, but it puts a new burden on
      beneficiaries to be smart shoppers.

PMID- 16440455
TI  - Burning in the house: carbon monoxide poisoning. An inexpensive alarm will give
      you some warning--and save your life.

PMID- 16440456
TI  - Decoding politics.

PMID- 16440457
TI  - By the way, doctor. I am a 73-year-old male. I've been diabetic for 50 years, and
      had a quintuple bypass eight years ago. I try to get an hour of exercise on a
      treadmill each day. While working out a couple of days ago, I developed a sudden
      sharp pain on my left side at about chest level, toward my back. Naturally I
      stopped, but I wondered when a person like me should call 911.

PMID- 16440458
TI  - How to aim for 5 extra years of life. Here's the possible payoff from fighting
      major cardiovascular risks.

PMID- 16440459
TI  - December is the cruelest month for heart attacks.

PMID- 16440460
TI  - How to get the best heart info. Free or low-cost: a home library from sources you
      can trust.

PMID- 16440461
TI  - Which drug for hypertension? Doctors often enroll multiple medications to fight a
      killer.

PMID- 16440463
TI  - I had an ultrasound of my heart recently, and the technician performing it
      wouldn't tell me anything about what he saw. He said I would have to wait for my
      doctor to call me. It's been two days now, and I'm still waiting. Don't you think
      patients should be able to get a least some preliminary information sooner? The
      same thing happened to me last year when I had an MRI.

PMID- 16440462
TI  - To fly without fear, plan ahead. How to guard your cardiovascular health on a
      long-haul trip.

PMID- 16440464
TI  - Preventing high blood pressure. Taking action can help.

PMID- 16440465
TI  - Health tips. Protect your teeth.

PMID- 16440466
TI  - Red wine may influence prostate cancer risk.

PMID- 16440467
TI  - Forgiveness and health. An act of healing.

PMID- 16440468
TI  - Rabies. Deadly but preventable.

PMID- 16440469
TI  - My 14-year-old grandson is embarrassed by warts on his hand. I recall hearing
      something about using duct tape as a treatment for warts. Is that possible?

PMID- 16440470
TI  - Helping practitioners understand the contribution of qualitative research to
      evidence-based practice.

PMID- 16440471
TI  - Reflections on "Helping practitioners understand the contribution of qualitative
      research to evidence-based practice".

PMID- 16440472
TI  - Making ethical choices: a comprehensive decision-making model for Canadian
      psychologists.
AB  - This paper proposes a theoretical augmentation of the seven-step decision-making
      model outlined in the Canadian Code of Ethics for Psychologists. We propose that
      teleological, deontological, and existential ethical perspectives should be taken
      into account in the decision-making process. We also consider the influence of
      individual, issue-specific, significant-other, situational, and external factors
      on ethical decision-making. This theoretical analysis demonstrates the richness
      and complexity of ethical decision-making.

PMID- 16440473
TI  - When reviews attack: ethics, free speech, and the peer review process.
AB  - The peer review process, whether formally applied in publication and grant
      review, or informally, such as exchange of ideas in scientific and professional
      newsgroups, has sparked controversy. Writers in this area agree that scholarly
      reviews that are inappropriate in tone are not uncommon. Indeed, commentators
      have suggested rules and guidelines that can be used to improve the review
      process and to make reviewers more accountable. In this paper, we examine the
      relevance and impact of ethical codes on the conduct of peer review. It is our
      contention that the peer review process can be improved, not by a new set of
      rules but through closer attention to the ethical principles to which we, as
      psychologists, already subscribe.

PMID- 16440474
TI  - Should imperfect infants survive? The 'Baby Doe' regs.

PMID- 16440476
TI  - Climate-change challenge continues.

PMID- 16440477
TI  - Decision rule can help identify children at lower risk for appendicitis.

PMID- 16440475
TI  - Treated and treatment-naive alcoholics come from different populations.
AB  - In most research on alcoholism, convenience samples of individuals who have been
      in some type of treatment are used. Berkson's fallacy results when the
      associations found in studies of select samples are incorrectly presumed to apply
      to all alcoholics (i.e., including untreated alcoholics in the general
      population). In the current study, we examined whether treated and untreated
      alcoholics have similar early alcohol use histories by comparing abstinent
      alcoholics (treated and sober at least 6 months) with treatment-naive alcoholics
      (active drinkers). We studied 14 pairs of women and 25 pairs of men matched on
      the age at which they first met criteria for heavy alcohol use (women, 80 drinks
      per month; men, 100 drinks per month). The timeline follow-back interview method
      was used to gather retrospective alcohol use information. Alcohol dose and
      duration of use were subsequently computed for two intervals: (1) time between
      the person's first drink and date at which the person met criteria for heavy
      drinking and (2) period between when criteria for heavy drinking were met and
      current age of the treatment-naive person from each pair. During the period
      before the matching "heavy drinking" criteria were met, alcohol dose did not
      differ between groups. In the period after criteria for heavy alcohol use were
      met, in comparison with treatment-naive alcoholics, the treated alcoholics had
      higher average and peak alcohol doses. We rejected the hypothesis that the
      treatment-naive alcoholics and the treated alcoholics have similar alcohol use
      trajectories over time, with the treatment-naive sample simply being observed
      earlier in its alcohol use histories. Instead, we concluded that the two groups
      come from different populations with regard to alcohol use. In fact, the treated
      alcoholics had alcohol doses more than 50% higher than those of treatment-naive
      alcoholics in the years just after they began drinking heavily. This finding
      supports the suggestion that results from studies of alcoholics in treatment or
      after treatment (i.e., most studies of alcoholics) cannot be generalized to
      untreated individuals (who make up the majority of alcoholics).

PMID- 16440478
TI  - More people accept animal research.

PMID- 16440479
TI  - Buccal midazolam is effective for acute treatment of seizures.

PMID- 16440480
TI  - Stellar insights.

PMID- 16440481
TI  - Probiotics help reduce severity of atopic dermatitis.

PMID- 16440482
TI  - Chequered spread.

PMID- 16440483
TI  - Tympanostomy tubes do not improve developmental outcomes.

PMID- 16440484
TI  - Q and A.

PMID- 16440485
TI  - Rainforest mammal surprise.

PMID- 16440486
TI  - Bibliography. Current world literature. Circulation and hemodynamics.

PMID- 16440487
TI  - [General theory of the action of some glycoside hydrolases].

PMID- 16440488
TI  - Retirement: privately coming undone.

PMID- 16440489
TI  - Gastric glassy cells: a study of 3202 gastrectomy specimens from dwellers of the
      Atlantic and Pacific basins.
AB  - Fifteen years ago we detected gastric cells with glassy cytoplasm (GCs) in the
      human pyloric antrum. The frequency of these cells was subsequently investigated
      in sections from gastrectomies carried on in populations dwelling on the rim of
      the Atlantic and Pacific basins. In this work we compared the results obtained in
      these disparate geographic regions. We reviewed sections from 3203 gastrectomies
      (1942 in the Atlantic basin and 1261 in the Pacific basin). In the Atlantic basin
      12/1942 (0.6%) of the gastrectomies had GCs, whereas in the Pacific basin 26/1261
      (2.1%) of the gastrectomies had GCs. The difference was significant (p<0.05). The
      proportion of gastrectomies with GCs was higher in patients in Vancouver, Canada,
      than in New York, and higher in Santiago de Chile than in Buenos Aires, despite
      the fact that these populations reside at approximately the same geographic
      latitude. Previous studies with the same material indicated that both the
      extension of intestinal metaplasia and the frequency of ciliated metaplasia were
      significantly higher in the Pacific than in the Atlantic basin. Hence, the
      difference in the frequencies of GCs appears to be a new indication that
      dissimilar environmental exposures in the two basins might have influenced the
      histological make-up of the gastric mucosa.

PMID- 16440491
TI  - [H. pylori update].

PMID- 16440492
TI  - [From unstable to hyperactive bladder].

PMID- 16440493
TI  - [How should one measure treatment efficacy of hyperactive bladder].

PMID- 16440494
TI  - [Evaluation perspective of hyperactive bladder, physiopathology and role of
      urgency].

PMID- 16440495
TI  - [Therapeutic strategy and impact of new treatments].

PMID- 16440496
TI  - [Needs and waiting for better management of hyperactive bladder].

PMID- 16440497
TI  - [Role of erythropoietin in brain homeostasis, neurodevelopment and
      neuroprotection].
AB  - Erythropoietin is known as a cytokine regulating the erythrocyte production.
      Based on recent research it became clear that it is secreted not only by the
      kidney, but by the central nervous system as well, and erythropoietin receptors
      are present there, too. Animal and human studies found that the expression of
      erythropoietin and its receptor is changing through neurodevelopment, which has
      impact on the differentiation of neuronal cells and is essential for normal
      neurodevelopment. In addition erythropoietin is protective against several
      mechanisms of neuronal injury: it alleviates the outcome of hypoxia and glutamate
      toxicity and has antiapoptotic effects. Based on these results the
      neuroprotective effects of exogenously administered erythropoietin was studied in
      several clinical studies. The available data indicate that erythropoietin or its
      analogues may have a role in neuroprotection in clinical settings.

PMID- 16440498
TI  - [Association of systemic lupus erythematosus and Sjogren's syndrome].
AB  - INTRODUCTION: Systemic lupus erythematosus and Sjogren's syndrome are
      multisystemic autoimmune diseases which can be associated to each other.
      OBJECTIVE: To investigate if there are any distinct clinical, laboratory or
      serologic features due to the association of the two diseases that can influence
      the follow up of these patients. PATIENTS AND METHODS: The authors proved the
      association of these two autoimmune diseases in 56 patients, and these patients'
      clinical, laboratory and immunoserologic alterations. 50 patients with Sjogren's
      syndrome and 50 patients with systemic lupus erythematosus were used as control
      groups. RESULTS: Compared with Sjogren's syndrome alone, in the cases of the
      association of the diseases, rheumatoid factor was present less frequently, Ro/SS
      A, La/SS-B and DNA antibodies were present more frequently, such as
      antiphospholipid autoantibodies and antiphospholipid syndrome. Anaemia,
      leukopenia and lymphopenia were detected more often and the patients were younger
      than in Sjogren's syndrome. Also, affection of the lung, kidney, skin, central
      nervous system and serous membranes are more common. The group with systemic
      lupus erythematosus differs in being older, having thyroiditis, Ro/SS-A, La/SS-B
      and DNA more frequently. CONCLUSION: Definitive clinical, laboratory and
      serological features make the difference between the association of the two
      diseases and the diseases observed alone.

PMID- 16440499
TI  - [Failure of diagnosing pancreatic tumors in the course of laparoscopic
      cholecystectomy: surgical lessons].
AB  - INTRODUCTION: In Hungary surgeons perform approximately 24000 cholecystectomies
      per year. Nowadays the choice of treatment of uncomplicated cholelithiasis is
      laparoscopic cholecystectomy. The advantages and popularity of the procedure are
      well known; otherwise the exploration of the abdominal cavity is not so complete
      than during open surgery. In the course of laparoscopic surgery the surgeon has
      minimal chance to find the preoperatively not diagnosed tumour. AIMS: In our
      retrospective study we analysed those complains and clinical signs, when we
      suspect the presence of a pancreas tumour. PATIENTS AND METHODS: We analysed the
      clinical data of patients who were operated on with pancreatic tumor and before
      the surgery, laparoscopic cholecystectomy had been performed in the previous 24
      month. RESULTS: In the period of 1996-2003 we operated 1515 patients with
      pancreatic tumor, at our clinic. 21 patients (1.39%) had laparoscopic
      cholecystectomy in the last 24 month, before the surgery. The age of the patients
      was between 50-78 (average age 65), the rate of the female and male patients was
      15/6. Most of the patients had weight loss (in 11 cases it was considerable, 5.4
      kg in one month) and the uncertain abdominal pain, feeling of discomfort,
      meteorism was also characteristic of these patients. In 16 cases (76%) the blood
      glucose level had been elevated. The ultrasound examination before the
      cholecystectomy in these cases was focused to the gall bladder. After the
      cholecystectomy, complains did not disappear definitely and further diagnostic
      steps verified the pancreatic tumour. The average time between the laparoscopic
      cholecystectomy and the open surgery was 10 month. In 4 cases we were able to
      remove the tumor, but in 17 cases only palliative operation was performed.
      CONCLUSIONS: If the patient is over the age of 50, especially if he is male, has
      weight loss and if the symptoms are not characteristic of gallbladder disease,
      further diagnostic steps are necessary before cholecystectomy. Complains
      remaining after laparoscopic cholecystectomy must be indication for urgent
      diagnostic steps. The life expectancy of patients with advanced pancreatic tumor
      is very poor.

PMID- 16440500
TI  - [Rickettsia helvetica: an emerging tick-borne pathogen in Hungary and Europe].
AB  - Rickettsia helvetica belonging to spotted fever group rickettsiae was recently
      detected by polymerase chain reaction followed by sequencing in European sheep
      ticks (Ixodes ricinus) from Hungary. Current knowledge on these rickettsiae and
      the clinical and diagnostic aspects of R. helvetica infection is summarized. In
      acute cases, R. helvetica is generally responsible for flu-like symptoms.
      Nevertheless, recent data indicate that in chronic cases, these rickettsiae can
      be responsible for perimyocarditis resulting sudden cardiac death and might play
      a role in the pathogenesis of aortic valve disease. The diagnosis can be based on
      serological, molecular and histological methods. A summary of the information
      available from Hungary and neighbouring countries on the prevalence of tick-borne
      encephalitis virus, Anaplasma, Borrelia, Francisella, Rickettsia and Babesia
      infections in I. ricinus is also presented.

PMID- 16440501
TI  - [History of the Hungarian hepatology in the 2nd part of the 20th century and
      today].

PMID- 16440502
TI  - [Debate about settling the midwife problem on the turn of the 19th and 20th
      centuries--Gusztav Dirner (1855-1912), Tauffers main partner in the debate, was
      born 150 years ago].

PMID- 16440503
TI  - Aerobic exercise adaptations in trained adolescent runners following a season of
      cross-country training.
AB  - Adaptations in aerobic exercise responses as well as the relationship between
      aerobic exercise responses and running performance were examined in a group of
      previously trained adolescent runners (n = 9; 15.9 +/- 1.0 years) over the course
      of a competitive cross-country season. Running economy (RE), submaximal blood
      lactate concentration [BLa] and VO2max were assessed before and immediately after
      the season. Five-km race time improved (P < 0.05) from 18.68 +/- 1.10 min at the
      beginning of the season to 18.16 +/- 1.11 min at the end of the season.
      Significant increases were observed in peak VO2 (61.6 +/- 3.5 to 65.3 +/- 2.9 mL
      x kg(-1) x min(-1)) and graded exercise test time (11.32 +/- 1.56 to 12.22 +/-
      0.79 min). There was a tendency for RE (P = 0.051) to worsen slightly and for
      [BLa] (P = 0. 057) to decline as a result of training. At the beginning of the
      season submaximal [BLa] at 14 km x hr(-1) (r = 0.86) and graded exercise test
      time (r = -0.87) were significantly related to 5-km time. At the end of the
      season, RE (r = 0.78) and [BLa] (r = 0.77) at 14 km x hr(-1) and graded exercise
      test time (r = -0.69) were significantly related to race time. In this well
      trained group of runners, further training during the cross-country season
      increased peak VO2 and improved race time. Submaximal [BLa] and graded exercise
      test time appear to be the most robust predictors of performance, while RE became
      a significant predictor of race time at the end of the season.

PMID- 16440504
TI  - Plasma glutamine responses to high-intensity exercise before and after endurance
      training.
AB  - Glutamine responses to strenuous interval exercise were examined before and after
      6 weeks of endurance training. Glutamine measures were obtained before and after
      the interval exercise sessions and training in untrained males assigned to
      training (T; n = 10) or control (C; n = 10) groups. Before training, C and T
      group glutamine progressively decreased (p < 0.05) by 18% and 16%, respectively,
      by 150-min postinterval exercise. Over the training period C group glutamine did
      not change, while T group values increased (p < 0.05) by 14%. After training,
      glutamine again decreased (p < 0.05) by similar percentages (C = 16% and T = 15%)
      by 150-min postinterval exercise, but the T group recorded higher (p < 0.05)
      resting and postexercise glutamine concentrations than the C group. Training
      induced increases in glutamine may prevent the decline in glutamine levels
      following strenuous exercise falling below a threshold where immune function
      might be acutely compromised.

PMID- 16440505
TI  - Myosin heavy chain isoform expression: influence on isoinertial and isometric
      performance.
AB  - Thirty-six healthy men with varying degrees of physical training background
      performed maximal-effort isometric and isoinertial knee extensor actions, with
      relative loads equal to 40% and 70% of one-repetition maximum. Force, velocity,
      and power were derived from force and linear position transducers at 500 Hz.
      Biopsies were taken from the vastus lateralis and analyzed by SDS-PAGE for
      relative myosin heavy chain (MHC) content. Relative MHC IIx content was included
      in a regression model, and explained variance noted. Relative MHC I content was
      subsequently added to the regression model to determine what, if any, additional
      variance was explained beyond that of MHC IIx. Results indicated that no
      relationship (r = 0.0 to 0.1) exists between the relative expression of MHC
      isoforms from the vastus lateralis and isometric/isoinertial performance in a
      population with diverse training backgrounds. Lack of nervous system adaptations
      in the untrained subjects in the study possibly attenuates the significant
      relationship between MHC and in-vivo muscle performance previously established in
      trained populations.

PMID- 16440507
TI  - Mechanics of a rope-braked cycle ergometer flywheel and its use for physiological
      measurement.
AB  - The cycle ergometer is one of the main tools used by physiologists in studies
      involving the measurement of work or power against physiological criteria. The
      current mechanical analysis of a Monark 824E rope-braked ergometer is based on a
      simplified approach. In this study a detailed analysis of the system is adopted
      to increase understanding. The mechanics of the ergometer flywheel are explained
      using data generated experimentally and the detailed components of the values of
      work that comprise the total work done by a subject are discussed. The total work
      done by a subject in 2.5 minutes at a speed of 60 rpm against a brake mass of 3
      kg was 23,034 J compared with the value of 27,000 J that normally would be
      attributed using the traditional calculations. This 15% difference is mainly due
      to the incorrect assumption that the brake load is the force due to the basket
      mass.

PMID- 16440508
TI  - Influence of familiarization on a backward, overhead medicine ball explosive
      power test.
AB  - This study examined the influence of familiarization with the backward, overhead
      medicine ball throw test of explosive power. Male rugby players (N = 28) aged 15
      to 16 (M +/- SD = 15.1 +/- 0.5) years completed the medicine ball throw six
      times. Repeated measures ANOVA indicated that the distance thrown differed across
      trials (F5,135 = 12.83, p < 0.01). Least significant differences post hoc
      multiple comparisons revealed significant differences between a number of trials;
      however, no significant difference was evident between the fifth and sixth trials
      (Mdiff = .005, p > 0.05). Typical error of measurement became less as trials
      progressed, with the typical error of measurement being 0.10 m between the fifth
      and sixth trials indicating little within subject variation between medicine ball
      throws following a familiarization period. The backward, overhead medicine ball
      throw may be a practical, reliable method to assess total body, explosive power
      of male teen-aged rugby players; however, completion of at least 5 to 6 practice
      trials is suggested for participants to obtain a stable score.

PMID- 16440506
TI  - Effect of Alpine ski boot cuff release on knee joint force during the backward
      fall.
AB  - The modern rigid alpine ski boot has been associated with an increase in severe
      knee joint injuries. A new design that allows the rear portion of the upper cuff
      of the boot (rear spoiler) to open when a posterior directed force is applied to
      it (similar to when a skier falls back on the ski) is investigated. Motion
      analysis was combined with kinetic measures to estimate the shear and compressive
      forces at the knee joint using a link-segment model while subjects fell backward
      to provoke ski boot cuff release. The rear spoiler opening was found to reduce
      anterior cruciate ligament directed shear force while increasing compressive
      force at the joint. We conclude that both compressive force and reduced anterior
      cruciate directed shear force have been associated with protective mechanisms at
      the knee joint. This occurred over a very brief period of time, however, and the
      influence this may have on knee injury prevention is discussed.

PMID- 16440509
TI  - Calcium channel blocker ingestion: an evidence-based consensus guideline for out
      of-hospital management.
AB  - In 2003, U.S. poison control centers were consulted after 9650 ingestions of
      calcium channel blockers (CCBs), including 57 deaths. This represents more than
      one-third of the deaths reported to the American Association of Poison Control
      Centers' Toxic Exposure Surveillance System database that were associated with
      cardiovascular drugs and emphasizes the importance of developing a guideline for
      the out-of-hospital management of calcium channel blocker poisoning. The
      objective of this guideline is to assist poison center personnel in the
      appropriate out-of-hospital triage and initial management of patients with
      suspected ingestions of calcium channel blockers. An evidence-based expert
      consensus process was used to create this guideline. This guideline applies to
      ingestion of calcium channel blockers alone and is based on an assessment of
      current scientific and clinical information. The expert consensus panel
      recognizes that specific patient care decisions may be at variance with this
      guideline and are the prerogative of the patient and the health professionals
      providing care, considering all of the circumstances involved. The panel's
      recommendations follow. The grade of recommendation is in parentheses. 1) All
      patients with stated or suspected self-harm or the recipient of a potentially
      malicious administration of a CCB should be referred to an emergency department
      immediately regardless of the amount ingested (Grade D). 2) Asymptomatic patients
      are unlikely to develop symptoms if the interval between the ingestion and the
      call is greater than 6 hours for immediate-release products, 18 hours for
      modified-release products other than verapamil, and 24 hours for modified-release
      verapamil. These patients do not need referral or prolonged observation (Grade
      D). 3) Patients without evidence of self-harm should have further evaluation,
      including determination of the precise dose ingested, history of other medical
      conditions, and the presence of co-ingestants. Ingestion of either an amount that
      exceeds the usual maximum single therapeutic dose or an amount equal to or
      greater than the lowest reported toxic dose, whichever is lower (see Table 5),
      would warrant consideration of referral to an emergency department (Grade D). 4)
      Do not induce emesis (Grade D). 5) Consider the administration of activated
      charcoal orally if available and no contraindications are present. However, do
      not delay transportation in order to administer charcoal (Grade D). 6) For
      patients who merit evaluation in an emergency department, ambulance
      transportation is recommended because of the potential for life-threatening
      complications. Provide usual supportive care en route to the hospital, including
      intravenous fluids for hypotension. Consider use of intravenous calcium,
      glucagon, and epinephrine for severe hypotension during transport, if available
      (Grade D). 7) Depending on the specific circumstances, follow-up calls should be
      made to determine outcome at appropriate intervals based on the clinical judgment
      of the poison center staff (Grade D).

PMID- 16440511
TI  - Murshidabad--one of the nine groundwater arsenic-affected districts of West
      Bengal, India. Part II: dermatological, neurological, and obstetric findings.
AB  - INTRODUCTION: To understand the severity of related health effects of chronic
      arsenic exposure in West Bengal, a detailed 3-year study was carried out in
      Murshidabad, one of the nine arsenic-affected districts in West Bengal. METHODS:
      We screened 25,274 people from 139 arsenic-affected villages in Murshidabad to
      identify patients suffering from chronic arsenic toxicity for evidence of
      multisystemic features and collected biological samples such as head hair, nail,
      and spot urine from the patients along with the tubewell water they were
      consuming. RESULTS: Out of 25,274 people screened, 4813 (19%) were registered
      with arsenical skin lesions. A case series involving arsenical skin lesions
      resulting in cancer and gangrene were noted during this study. Representative
      histopathological pictures of skin biopsy of different types of lesions were also
      presented. Out of 2595 children we examined for arsenical skin lesions, 122 (4%)
      were registered with arsenical skin lesions, melanosis with or without keratosis.
      Different clinical and electrophysiological neurological features were noticed
      among the arsenic-affected villagers. Both the arsenic content in the drinking
      water and duration of exposure may be responsible in increasing the
      susceptibility of pregnant women to spontaneous abortions, stillbirths, preterm
      births, low birth weights, and neonatal deaths. Some additional multisystemic
      features such as weakness and lethargy, chronic respiratory problems,
      gastrointestinal symptoms, and anemia were also recorded in the affected
      population. DISCUSSION: The findings from this survey on different health effects
      of arsenic exposure were compared to those from previous studies carried out on
      arsenic-affected populations in India and Bangladesh as well as other affected
      countries. CONCLUSION: Multisystemic disorders, including dermal effects,
      neurological complications, and adverse obstetric outcomes, were observed to be
      associated with chronic arsenic exposure in the study population in Murshidabad,
      West Bengal. The magnitude of severity was related to the concentration of
      arsenic in water as well as duration of the exposure.

PMID- 16440512
TI  - Determining triage guidelines for unintentional overdoses with calcium channel
      antagonists.
AB  - BACKGROUND: Calcium channel antagonists (CCAs) are known to cause significant
      toxicity in overdose. Determining triage guidelines for CCAs is an important but
      difficult task. This study was designed to determine if an unintentional overdose
      of a patient's CCA could result in clinically significant cardiovascular (CV)
      symptoms (hypotension, bradycardia, conduction disturbances). METHODS: Poison
      center records over a 3-year period were reviewed for adults ingesting at least
      double their prescribed dose of CCAs and who were evaluated in an emergency
      department (ED). Cases were reviewed for: patient age and gender, co-ingestants,
      CCA involved, dosage form, dose taken, usual dose, symptoms, available vital
      signs, and medical outcomes. RESULTS: 225 cases were identified; 161 cases met
      study criteria. There were 51 cases involving co-ingestants and 13 in which the
      usual dose was unknown. These were excluded. One hundred twenty-two patients
      (76%) were female and the mean age of all patients was 64 years. One hundred and
      four (65%) cases involved ingestions equal to double the usual dose (DD), 57
      (35%) involved more than a DD. For DD cases, nine (9%) developed clinically
      significant CV signs or symptoms; while in cases with more than DD, eight (14%)
      did. CONCLUSIONS: This retrospective review demonstrated that the toxicity of
      CCAs following a therapeutic overdose can be highly variable and that the dose
      producing a toxic effect on the cardiovascular system may be within the maximum
      range of therapeutic doses. This may be the result of a number of factors,
      including the broad range of therapeutic doses as well as the pre-existing
      conditions in patients taking these medications. This variability makes home
      management of these cases difficult and therefore, poison centers should be
      conservative in their evaluation of these cases.

PMID- 16440510
TI  - Murshidabad--one of the nine groundwater arsenic-affected districts of West
      Bengal, India. Part I: magnitude of contamination and population at risk.
AB  - INTRODUCTION: To understand the severity of the arsenic crisis in West Bengal,
      India, a detailed, 3-year study was undertaken in Murshidabad, one of the nine
      arsenic-affected districts in West Bengal. The district covers an area of 5324
      km2 with a population of 5.3 million. METHODS: Hand tubewell water samples and
      biologic samples were collected from Murshidabad and analyzed for arsenic by FI
      HG-AAS method. Inter laboratory analysis and analyses of standards were
      undertaken for quality assurance. RESULTS: During our survey we analyzed 29,612
      hand tubewell water samples for arsenic from both contaminated and non
      contaminated areas, and 26% of the tubewells were found to have arsenic above 50
      microg/L while 53.8% had arsenic above 10 microg/L. Of the 26 blocks in
      Murshidabad, 24 were found to have arsenic above 50 microg/L. Based on our
      generated data we estimated that approximately 0.2 million hand tubewells are
      installed in all 26 blocks of Murshidabad and 1.8 million in nine arsenic
      affected districts of West Bengal. It was estimated on the basis of our data that
      about 2.5 million and 1.2 million people were drinking arsenic-contaminated water
      with concentrations above 10 and 50 microg/L levels respectively in this
      district. The analysis of total 3800 biologic (nail, urine, and hair) samples
      from arsenic-affected villages revealed that 95% of the nail and 94% of the urine
      samples contained arsenic above the normal levels and 75% of the hair samples
      were found to have arsenic above the toxic level. Thus, many villagers in the
      affected areas of Murshidabad might be subclinically affected. DISCUSSION AND
      CONCLUSION: Comparing our extrapolated data with international dose response
      results, we estimated how many people may suffer from arsenical skin lesions and
      cancer. Finally, if the exposed population is provided safe water, better
      nutrition, and proper awareness about the arsenic problem, lives can be saved and
      countless suffering of the affected population can be avoided.

PMID- 16440513
TI  - Retrospective evaluation of tiagabine overdose.
AB  - BACKGROUND: Tiagabine is an anticonvulsant that blocks reuptake of the inhibitory
      neurotransmitter GABA. There are no published studies or case series of tiagabine
      overdoses. METHODS: The records of six poison centers and one statewide poison
      center network were searched for all exposures to tiagabine for the years 2000
      2002. Inclusion criterion was a human tiagabine exposure with follow-up to a
      known outcome; exclusion criterion was multiple drug ingestion. RESULTS: 57 cases
      met the inclusion criterion. Thirty-seven patients were female (67%). Mean and
      median ages were 30.5 years (S.D. +/- 18.5) and 31 years, respectively, with a
      range of 2 to 80 years. Seven patients were < or = 6 years. Neurologic symptoms
      were common: lethargy, seizures (multiple), status epilepticus, seizure (single),
      coma, confusion, agitation, tremors, dizziness, dystonias/abnormal posturing, and
      hallucinations. Other symptoms included respiratory depression, tachycardia,
      hypertension, and hypotension. Therapies included benzodiazepines, mechanical
      ventilation, phenytoin, phenobarbital, diphenhydramine, and dopamine. The mean
      onset and duration of symptoms were 1.3 hours (+/- 0.5, range 1-2 hours) and 9.1
      hours (+/- 3.8, range 4-24 hours), respectively. Dose ingested by history was
      known for 38 patients (67%). The lowest dose with the development of multiple
      seizures and coma was 96 mg. This occurred in a 36-year-old female with a history
      of epilepsy. The lowest dose with symptoms in a child was 8 mg, in a 6-year-old
      with drowsiness. Mean dose of those with and without symptoms was 102 mg and 10
      mg, respectively. The mean dose for patients experiencing seizures was 224 mg (+/
      172, range 96 to 680 mg). The mean dose for patients experiencing coma and
      respiratory depression was 270 mg (+/- 204, range 96 to 680 mg). Fifty-two
      patients (91%) were evaluated in the ED of whom 43 were admitted for medical
      care. CONCLUSION: Seizures and altered mental status were common with tiagabine
      overdose, with rapid onset and resolution of symptoms. In this series, seizures
      did not occur until the ingestion was greater than three times the maximum
      recommended daily dose.

PMID- 16440514
TI  - Three cases of substitution errors leading to hyoscine hydrobromide overdose.
AB  - We report three patients with anticholinergic poisoning caused by the
      substitution of hyoscine hydrobromide for hyoscine butylbromide in preparations
      compounded by two different pharmacists. The patients took the preparations for
      gastrointes tinal discomfort and presented with altered mental status
      tachycardia, facial flushing, dilated pupils, and dry skin shortly after the
      ingestion. In one patient the intoxication was initially not recognized and he
      was treated as suffering from an acute cerebrovascular accident. Two patients
      experienced long-lasting effects such as decreased ability to concentrate, memory
      dis turbances, tremor, and photo- and phonophobia. It was obviously impossible to
      elucidate the exact nature of the relationship between the intoxication and these
      long-lasting complaints. Information from the Belgian poison control center
      revealed that cases of substitution error with hyoscine hydrobromide are not
      unique The Belgian authorities issued a warning to all pharmacists.

PMID- 16440515
TI  - Intermediate syndrome following carbamate poisoning.

PMID- 16440516
TI  - Tiagabine overdose: a case of status epilepticus in a non-epileptic patient.
AB  - Tiagabine is an antiepileptic drug used as adjunctive therapy for partial
      seizures that is believed to selectively inhibit the presynaptic reuptake of
      gamma aminobutyric acid (GABA). We describe a case of a tiagabine overdose that
      resulted in status epilepticus (SE) in a patient with no seizure history. A 14
      year-old girl with a history of asthma presented with convulsive SE after
      ingestion of an unknown amount of her sister's tiagabine in a suicide attempt.
      Attempted anticonvulsant therapy included a total of diazepam 10 mg IV, lorazepam
      6 mg IV, pyridoxine 5 g IV, and fosphenytoin 20 mg PE/kg. All were without
      effect. A computed tomography and electrocardiogram were normal. Continuous
      bedside EEG monitoring showed suppression of seizure activity following
      intravenous midazolam. A tiagabine level obtained on ED arrival was 420 ng/mL
      (therapeutic 20-103 ng/mL). The patient was discharged to psychiatry within 1
      week with no neurologic sequelae.

PMID- 16440518
TI  - Scopolamine treatment for severe extra-pyramidal signs following organophosphate
      (chlorpyrifos) ingestion.
AB  - BACKGROUND: The use of competitive inhibitors of acetylcholine other than
      atropine, for patients with organophosphate poisoning is controversial. Because
      scopolamine ability to cross the blood-brain barrier is better than that of
      atropine, it has been suggested that it should be used in patients with
      organophosphate poisoning who have central nervous system manifestations. CASE
      DESCRIPTION: A 17-year-old girl was admitted to the pediatric ward after
      ingesting chlorpyrifos as a suicidal attempt. She reported vomiting three times.
      She had no other symptoms for 12 hours and then over the course of 36 hours
      gradually developed extrapyramidal signs and became comatose. She was treated
      with intravenous scopolamine. Within 3 minutes the patient started to respond to
      verbal commands and answered simple questions rigidity subsided, and she was able
      to sit in bed. She was discharged after 4 days with no neurological sequelae.
      CONCLUSIONS: We suggest, that in patients with organophosphate poisoning who have
      mainly central nervous system toxicity scopolamine administration might be
      considered.

PMID- 16440517
TI  - Severe acute poisoning with homemade Aconitum napellus capsules: toxicokinetic
      and clinical data.
AB  - Aconitum napellus is an extremely dangerous plant that contains various toxic
      diterpenoid alkaloids, mainly aconitine primarily concentrated in the roots. We
      report a case of acute intoxication of a 21-year-old man admitted to our
      Emergency Department after the ingestion, in order to sleep, of three homemade
      Aconitum napellus capsules. Capsules were measured to contain 237 mg of root and
      19 microg of aconitine. The patient experienced the first symptoms on wakening 5
      hours later with generalized paresthesia, nausea, diarrhea, vertigo, thoracic
      pain dyspnea, and dyschromatopsia. At admission, 7 hours after intake
      electrocardiographic analysis showed a sinusal bradycardia with polymorphic and
      bigeminal ventricular extrasystolia. Cardiovascular and neurological symptoms
      disappeared, respectively within 11 and 13 hours of ingestion. The patient was
      discharged from the ICU on day 2. Plasmatic concentrations at H7, H9, H14 H19,
      and after ingestion were, respectively, of 1.75, 0.75, 0.35, and 0.02 ng/mL. The
      calculated half-life of aconitine was 3 hours. To our knowledge, this is the
      first reported case with an aconitine toxicokinetic-effect relationship. The
      authors stress that clinicians must be aware of possible occurrence of acute
      poisoning with Aconitum napellus in European countries and in the United States
      as herbal medicine is becoming increasingly popular.

PMID- 16440519
TI  - 2005 Louis Roche lecture professional societies and evidence-based clinical
      toxicology delivered at the XXV international congress of the European
      Association of Poisons Centres and Clinical Toxicologists Berlin, Germany.

PMID- 16440520
TI  - Case report does not report sufficient data to support a diagnosis of fatal
      organophosphorus poisoning.

PMID- 16440521
TI  - Poisoning with rivastigmine.

PMID- 16440522
TI  - Stinging catfish poisoning.

PMID- 16440523
TI  - On the cover: Epicoccum pupurascens.

PMID- 16440524
TI  - Diagnostic testing for allergies.

PMID- 16440525
TI  - Diagnostic venom skin tests and venom specific IgE assays: do we need to worry?

PMID- 16440526
TI  - The reading, writing, and arithmetic of the medical literature, part 3: critical
      appraisal of primary research.
AB  - OBJECTIVE: To offer suggestions that will help clinicians improve their scrutiny
      of the medical literature and apply these suggestions to their own medical
      writings. DATA SOURCES: Literature searches began at the National Library of
      Medicine's online database and were traced to primary sources. STUDY SELECTION:
      Studies were selected for their ability to provide historical background, discuss
      the aspects of study design and statistical analysis, and explore important
      facets of reading and writing medical manuscripts. RESULTS: Physician readers
      will become more proficient in their skills as both users and creators of the
      medical literature. CONCLUSIONS: Reading and interpretation of the medical
      literature requires a set of skills that can be learned. Similarly, good medical
      writing skills can be developed. Achieving these skills will enhance the
      clinician's practice of medicine.

PMID- 16440527
TI  - Skin testing: a survey of allergists.
AB  - BACKGROUND: In the allergist's office, skin testing remains the central way to
      confirm allergic response. Although anecdotal data suggest widely varying
      practices in skin testing by allergists, the diversity and relative frequency of
      these practices have not been documented. OBJECTIVE: To determine the extent of
      the diversity in skin testing practices among allergists. METHODS: A
      questionnaire was sent via the Internet to all physician members and fellows of
      the American College of Allergy, Asthma and Immunology who practice in the United
      States. This survey explored choice of extract concentrations, skin test device,
      number and type of tests, method for interpretation and documentation of skin
      test results, and quality assurance procedures used. RESULTS: Overall, a
      significant degree of variability was reported with regard to number of skin
      tests performed, extract concentrations, skin test devices, interpretation and
      documentation of results, and quality assurance procedures. The average number of
      skin prick tests performed ranged from 5.09 (grasses) to 10.9 (trees), whereas
      the average number of intradermal tests performed ranged from 2.03 (grasses) to
      5.6 (perennial). The allergen extract concentrations used for intradermal testing
      varied widely. Expressed as a dilution of the concentrated extracts, 20.8% use
      1:100 dilutions, 10.3% use 1:500 dilutions, and 59.4% use 1:1,000 dilutions.
      Significant variability also occurred regarding devices and the technique with
      which the devices were used. Most clinicians (92.1%) used the most concentrated
      extract available for skin prick testing. For reporting the results of skin
      testing, 53.8% used a 0 to 4+ scale, and only 28.3% measured orthogonal
      diameters. Of those using a 0 to 4+ scale, two thirds related the results to the
      size of the histamine control. Quality assurance testing was reportedly performed
      by 61.2% of responders. However, less than 10% of responders used an objective
      test protocol for this purpose. CONCLUSIONS: This survey highlights some of the
      areas that allergists can improve on in the use and reporting of skin tests.

PMID- 16440528
TI  - Reproducibility of skin testing and serum venom specific IgE in Hymenoptera venom
      allergy.
AB  - BACKGROUND: The decision regarding an immunotherapy regimen for venom-allergic
      patients is based on the results of skin testing and serum venom specific IgE
      measurements. However, their reliability has been questioned, and their
      reproducibility has not been examined. OBJECTIVE: To evaluate the reproducibility
      and reliability of the results of skin testing and serum venom specific IgE
      measurement in venom-allergic patients. METHODS: Patients with a systemic
      reaction after an insect sting were evaluated twice, 2 to 6 weeks apart, by
      intradermal skin tests and by determination of serum venom specific IgE to
      Hymenoptera venoms. RESULTS: Thirty-five patients were evaluated 1 to 168 months
      (mean, 23 months) after the sting reaction. Reproducibility of skin test results
      for all venoms at the 2 sessions was found in 23 patients (66%). Reproducibility
      of venom specific IgE results for all venoms was found in 16 (59%) of 27 patients
      from whom 2 blood samples were available for evaluation. Concordance between skin
      test and venom specific IgE results for all venoms was found in 30 (51%) of 59
      samples available for evaluation. CONCLUSIONS: The reproducibility of venom skin
      test and serum venom specific IgE results is relatively poor. It is common
      practice for therapeutic decisions regarding venom immunotherapy to be based on a
      single diagnostic evaluation. Consequently, many patients are either overtreated
      or undertreated. Better diagnostic methods are required in venom allergy.

PMID- 16440529
TI  - Effect of imported fire ant extract on the degradation of mountain cedar pollen
      allergen.
AB  - BACKGROUND: Dust mite, cockroach, and mold extracts have been shown to contain
      proteases capable of degrading the proteins in other extracts. Loss of potency of
      allergens has been reported in mixtures containing cockroach and fungal extracts.
      Fire ant venoms consist of 90% to 95% n-alkyl and n-alkenyl piperidine alkaloids,
      which are not allergenic. No studies are available addressing the mixture of
      imported fire ant (IFA) whole-body extract with other allergens or the presence
      of proteolytic activity in the venom extract. OBJECTIVES: To evaluate the
      stability of mountain cedar pollen extract mixed with IFA whole-body extract and
      to qualitatively analyze the extract mixture for degradation of mountain cedar
      protein. METHODS: One milliliter each of mountain cedar and IFA whole-body
      extracts at a concentration of 500 microg/mL were combined and stored at 4
      degrees C for 1, 3, 6, 15, 30, 60, 90, and 180 days. Separate mixtures of 1 mL of
      mountain cedar and IFA with 1 mL of human serum albumin were used as controls.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed, and
      protein bands were qualitatively analyzed for degradation. RESULTS: We detected 3
      distinct IFA protein bands and 1 mountain cedar protein band. With respect to
      these bands, no protein degradation was observed during 6 months of study in the
      extract mixture compared with the controls. CONCLUSIONS: Imported fire ant whole
      body extract does not seem to degrade mountain cedar protein. Mixtures of
      allergenic extracts may be able to include IFA whole-body extract.

PMID- 16440530
TI  - Anaphylaxis to omeprazole: diagnosis and desensitization protocol.
AB  - BACKGROUND: Omeprazole is an inhibitor of the parietal cell enzyme H+/K+
      adenosine triphosphatase. Immediate-type hypersensitivity reactions, such as
      urticaria, angioedema, and hypotension, induced by omeprazole and other proton
      pump inhibitors are rare. OBJECTIVES: To confirm the immediate-type mechanism of
      recurrent anaphylactic reactions to the repeated administration of omeprazole
      using skin testing and to enable safe administration of the drug after successful
      oral desensitization. METHODS: Intradermal skin tests were performed with
      omeprazole (0.04 and 0.4 mg/mL) prepared from the oral and intravenous commercial
      preparations and with pantoprazole (0.02 and 0.2 mg/mL) prepared from the oral
      commercial preparation. Skin tests were repeated after completion of the
      desensitization. Oral desensitization was applied at a starting dose of 0.001 mg
      of omeprazole, and a full dose of 16 mg was achieved after 5.6 hours (cumulative
      dose of 32.6 mg). RESULTS: Intradermal skin test results were positive to
      omeprazole and pantoprazole at all tested concentrations. After successful
      desensitization, omeprazole was administered in the full dose uneventfully. The
      wheal size of the intradermal skin tests performed after completion of the
      desensitization was significantly reduced. CONCLUSION: When indicated, this newly
      designed desensitization protocol may be used in patients with omeprazole-induced
      anaphylaxis.

PMID- 16440531
TI  - Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed
      to aeroallergens in the Vienna Challenge Chamber.
AB  - BACKGROUND: Rupatadine is a novel compound with potent dual antihistamine and
      platelet-activating factor antagonist activities and no sedative effects.
      OBJECTIVE: To evaluate the efficacy of rupatadine, 10 mg once daily, and placebo
      on allergen-induced symptoms (including nasal congestion), nasal airflow, nasal
      secretion, and subjective tolerability in response to grass pollen in a
      controlled allergen-exposure chamber. METHODS: In a randomized, double-blind,
      placebo-controlled, crossover trial, 45 patients with a history of seasonal
      allergic rhinitis received rupatadine or placebo every morning for 8 days in 2
      different periods separated by a 14-day washout interval. On day 8 of each
      crossover period, patients underwent a 6-hour allergen exposure in the Vienna
      Challenge Chamber, where a constant and homogeneous concentration of
      aeroallergens was maintained. Subjective and objective assessments were performed
      online during the exposure. RESULTS: Subjective single and composite nasal and
      nonnasal symptoms were consistently less severe with rupatadine use than with
      placebo use starting from the first evaluation at 15 minutes to the end of the 6
      hour Vienna Challenge Chamber challenge, with the most significant effects seen
      for nasal rhinorrhea, nasal itching, sneezing attacks, and total nasal symptoms
      (P < .001 for all). All the other symptoms (including nasal congestion, P < or =
      .005) were also significantly reduced with active treatment compared with placebo
      use. Mean secretion weights and overall feeling of complaint were significantly
      lower with rupatadine therapy than with placebo use (P < or = .001). Overall,
      rupatadine treatment was well tolerated. CONCLUSION: Rupatadine treatment is
      effective and well tolerated in patients with allergen-induced symptoms exposed
      to aeroallergens in a controlled exposure chamber.

PMID- 16440532
TI  - Vitamin E effects on nasal symptoms and serum specific IgE levels in patients
      with perennial allergic rhinitis.
AB  - BACKGROUND: Studies have shown that vitamin E intake may reduce IgE production.
      OBJECTIVE: To evaluate the effects of vitamin E supplementation on the severity
      of nasal symptoms and the serum levels of specific IgE in patients with perennial
      allergic rhinitis. METHODS: Sixty-three patients (mean +/- SD age, 12 +/- 2.4
      years) with a history of perennial allergic rhinitis participated in this study.
      None of the patients had evidence of acute infectious disease or used tobacco,
      corticosteroids, antihistamines, or vitamins. Patients were randomized to receive
      either vitamin E (400 IU/d) or placebo for 4 weeks, with loratadine
      pseudoephedrine (0.2/0.5 mg/kg) during the first 2 weeks of treatment. The
      severity of nasal symptoms was evaluated using a validated questionnaire, which
      was administered weekly for 4 weeks. The serum concentrations of specific IgE to
      5 common inhalant allergens and lipid peroxides were measured before treatment
      and at the end of the study. RESULTS: Before, during, and after treatment, the
      symptom severity scores were similar in the 2 groups; within each group, a
      significant decrease was observed after the first week of follow-up (P < .05),
      with no further changes. Serum levels of specific IgE and lipid peroxides did not
      show any significant changes related to vitamin E intake within and between
      groups. CONCLUSIONS: In patients with perennial allergic rhinitis, vitamin E
      supplementation (400 IU/d) did not have any significant effects on nasal symptom
      severity or on serum concentrations of specific IgE to 5 common allergens.

PMID- 16440533
TI  - Fluticasone propionate hydrofluoroalkane inhalation aerosol in patients receiving
      inhaled corticosteroids.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) delivered by metered-dose inhalers
      that contain chlorofluorocarbon propellants are being discontinued because of the
      harmful effects of chlorofluorocarbon on the ozone layer. Therefore, some metered
      dose inhaler products are being reformulated with "ozone-friendly"
      hydrofluoroalkane propellants. OBJECTIVE: To evaluate treatment with fluticasone
      propionate hydrofluoroalkane inhalation aerosol, 88, 220, and 440 microg twice
      daily, vs placebo in patients with asthma receiving an ICS. METHODS: Randomized,
      double-blind, parallel-group, 12-week study. RESULTS: Mean morning predose
      percent predicted forced expiratory volume in 1 second increased by 2.2%, 3.2%,
      and 4.6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily,
      groups, respectively, compared with an 8.3% decrease for placebo (P < .001 vs
      placebo for all groups). Secondary pulmonary function end points and asthma
      symptoms showed similar improvements compared with placebo. Discontinuation from
      the study due to lack of efficacy was 50% in the placebo group and 11%, 10%, and
      6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups,
      respectively. At week 12, the probability of remaining in the study was 0.89,
      0.90, and 0.94 for the fluticasone propionate, 88-, 220-, and 440-microg twice
      daily, groups, respectively, vs 0.45 for the placebo group (P < .001 for all).
      Changes in 24-hour urinary cortisol excretion rates were similar among treatment
      groups. CONCLUSIONS: Fluticasone propionate hydrofluoroalkane, previously shown
      to be a clinically suitable alternative to fluticasone propionate
      chlorofluorocarbon, was effective and well tolerated. The ability to switch from
      fluticasone propionate chlorofluorocarbon and other chlorofluorocarbon-containing
      ICSs to fluticasone propionate hydrofluoroalkane without sacrificing asthma
      control or tolerability will facilitate a smooth transition to this
      nonchlorofluorocarbon-containing medicinal.

PMID- 16440535
TI  - Physician-diagnosed asthma and allergic rhinitis in Manitoba: 1985-1998.
AB  - BACKGROUND: A worldwide increase has been noted in the prevalence of asthma, but
      the data for other allergic disorders are less consistent. OBJECTIVE: To study 14
      year trends in utilization of physician resources for asthma and compare them to
      trends for allergic rhinitis. METHODS: We studied visits to physicians by
      Manitoba residents for asthma (International Classification of Diseases, Ninth
      Revision, Clinical Modification [ICD-9-CM] code 493) and allergic rhinitis (ICD-9
      code 477) between 1985 and 1998. Prevalence and incidence of physician resources
      utilization were calculated annually for the total population and by age groups.
      Aggregate statistics and frequency of physician resources utilization were also
      analyzed. RESULTS: The prevalence and incidence of physician resources
      utilization for asthma increased more than for allergic rhinitis; differences
      were most striking in the youngest age groups. In adults, the differences were
      smaller and changed little with time. Most of the increase in asthma care
      occurred in children and in people without allergic rhinitis. Overall, 17% of
      Manitobans were diagnosed as having asthma, and the average asthmatic patient
      made 6 visits. Approximately 14% had an allergic rhinitis diagnosis, each person
      being seen twice on average. Coexistence of asthma and allergic rhinitis led to
      increased physician resources utilization for each of the conditions.
      CONCLUSIONS: Trends in utilization of physician resources for allergic rhinitis
      differed strikingly from trends for asthma, particularly in the youngest age
      group. Asthma and allergic rhinitis affected comparable proportions of the
      population, but a diagnosis of asthma resulted in much higher utilization of
      physician resources. The relationship of physician-diagnosed asthma and atopy, as
      indicated by the diagnosis of allergic rhinitis, appears to have weakened with
      time in children but not in adults.

PMID- 16440534
TI  - Efficacy of montelukast during the allergy season in patients with chronic asthma
      and seasonal aeroallergen sensitivity.
AB  - BACKGROUND: Montelukast has proven efficacy in the treatment of chronic asthma
      and seasonal allergic rhinitis, but it has not been evaluated in the
      subpopulation of asthmatic patients with seasonal asthma symptoms. OBJECTIVE: To
      determine the effectiveness of montelukast treatment in improving the control of
      asthma symptoms during the allergy season in patients with active asthma and
      seasonal aeroallergen sensitivity. METHODS: Adults with a history of chronic
      asthma who are also symptomatic during the allergy season and with skin test
      sensitivity to seasonal aeroallergens were enrolled in a randomized, parallel
      group, multicenter study with a 1-week, single-blind, placebo run-in period
      followed by 3 weeks of double-blind treatment during the spring of 2004. After
      the run-in period, eligible patients were randomly assigned to receive either
      oral montelukast (10 mg) or placebo. Daytime and nighttime asthma symptom scores,
      beta-agonist use, and morning and evening peak expiratory flow rates were
      recorded daily using an electronic diary. The primary end point was mean change
      from baseline to week 3 in the daytime asthma symptom score. RESULTS: Of 455
      randomized patients, 433 completed the study. Compared with placebo, treatment
      with montelukast resulted in a significant improvement from baseline in the
      daytime asthma symptom score (-0.54 vs -0.34; P = .002) and in beta-agonist use,
      nighttime symptoms, and peak expiratory flow rates. Few patients in the
      montelukast and placebo groups discontinued study participation because of asthma
      (1.3% and 3.0%, respectively). CONCLUSION: In patients with chronic asthma and
      seasonal aeroallergen sensitivity, montelukast treatment provided significant
      asthma control during the allergy season compared with placebo.

PMID- 16440536
TI  - Decreases in Hispanic and non-Hispanic asthma mortality.
AB  - BACKGROUND: Rates of death from asthma in the United States increased from 0.8
      per 100,000 general population in 1977-1978 to 2.1 in 1994-1996, but they have
      decreased since then to 1.5 in 2001. OBJECTIVE: To investigate changes in asthma
      mortality among Hispanics in the United States. METHODS: Collection and graphing
      of data from the National Center for Health Statistics identifying asthma
      (International Classification of Diseases, Tenth Revision codes J45-J46) as the
      underlying cause of death in the 50 United States and the District of Columbia
      among Hispanics and non-Hispanics. RESULTS: Deaths from asthma among Hispanics
      decreased from 320 in 1999 to 274 in 2001, whereas deaths among non-Hispanics
      decreased from 4,324 to 3,976. Rates of death from asthma among Hispanics
      decreased from 1.0 per 100,000 general population in 1999 to 0.7 in 2001, whereas
      those for non-Hispanics decreased from 1.84 to 1.6. Rates have been much higher
      for non-Hispanic blacks than for non-Hispanic whites but have decreased for both.
      Death rates from asthma have been higher among Hispanic females than males but
      have decreased for both. CONCLUSIONS: Asthma mortality in the United States has
      been decreasing since 1999 among Hispanics and non-Hispanics. These changes are
      consistent with better management of asthma.

PMID- 16440537
TI  - A culturally competent asthma management intervention: a randomized controlled
      pilot study.
AB  - BACKGROUND: Despite significant medical advances, many ethnic and racial minority
      children who live in inner cities continue to experience disproportionately high
      levels of asthma morbidity and mortality compared with white children. As a
      result, a growing number of psychosocial asthma management interventions are
      being developed to address their needs; however, only a few of these
      interventions have incorporated cultural variables into their treatments and have
      had their efficacy evaluated. OBJECTIVE: To examine the efficacy of the
      Multifamily Asthma Group Treatment (MFAGT), designed to enhance asthma management
      and reduce emergency department (ED) visits among African American and Hispanic
      families. METHODS: Twenty-four African American and Hispanic families who have
      children with asthma were randomly assigned to either the MFAGT or the Standard
      Psychoeducational Asthma Intervention. Differences in the number of ED visits and
      the level of asthma management in both groups were compared 1 year before and 1
      year after the intervention. In addition, these groups were contrasted to a
      control group that did not receive any psychoeducational intervention. RESULTS:
      The MFAGT was significantly (P = .04) more effective than the Standard
      Psychoeducational Asthma Intervention and the control in decreasing ED visits and
      increasing parental asthma knowledge. CONCLUSIONS: These preliminary results
      suggest that the MFAGT is efficacious in enhancing asthma management and in
      reducing ED visits in inner-city African American and Hispanic children from a
      lower socioeconomic background.

PMID- 16440538
TI  - Long distance transport of ragweed pollen as a potential cause of allergy in
      central Italy.
AB  - BACKGROUND: Ambrosia pollen is an important allergen in North America and, as
      recently discovered, in some European countries. In Italy, the most affected area
      is the northeast, whereas ragweed has not been reported in the central and
      southern parts of the country. OBJECTIVE: To identify the source of ragweed
      pollen detected in Florence and Pistoia in central Italy. METHODS: Ragweed pollen
      data were collected in Florence and Pistoia for a 6-year period (1999-2004). The
      relationship between pollen counts and local ground prevalent wind directions was
      evaluated with analysis of variance and the least significant difference test.
      Weather conditions were also evaluated on a large-scale circulation pattern by
      analyzing weather maps and air mass back trajectories. RESULTS: A highly
      statistically significant relationship between daily prevailing wind direction
      and pollen count was found in the period under investigation; the ragweed pollen
      peaks were recorded when winds from northeast in Florence and north-northeast in
      Pistoia were observed. The synoptic weather situation and the path of back
      trajectories suggest an area around southern Hungary as a possible source of
      Ambrosia pollen. Furthermore, the pollen count was above the clinical threshold
      several times in both Florence and Pistoia. CONCLUSIONS: Several factors indicate
      that the detection of ragweed pollen in central Italy is due to long distance
      transport. Taking into consideration the high allergenicity of Ambrosia pollen,
      the present findings, if confirmed, suggest that the number of sensitized
      individuals might significantly increase in the near future.

PMID- 16440539
TI  - Impact of occupational and inhalant allergy on rhinitis-specific quality of life
      in employees of bell pepper greenhouses in the Netherlands.
AB  - BACKGROUND: Rhinitis symptoms among bell pepper greenhouse employees can be
      caused by an allergy to occupational allergens, such as bell pepper pollen and
      predatory mites, and common inhalant allergens. OBJECTIVES: To estimate the
      effect of sensitization to these allergens on rhinitis-specific quality of life
      (QoL) during and outside the flowering period and to evaluate whether the QoL of
      sensitized employees is comparable with that of chrysanthemum greenhouse
      employees with rhinitis and an average population sample with perennial rhinitis.
      METHODS: We invited 233 employees with rhinitis symptoms to complete 2 rhinitis
      QoL questionnaires and to undergo skin prick testing with common inhalant
      allergens and occupational allergen extracts. Multiple regression analysis was
      used to estimate the impact of sensitization to the various allergens on QoL.
      RESULTS: Sensitization to bell pepper pollen had a significant negative effect on
      all the domain and mean QoL scores. The other allergens had no effect on QoL. A
      significant decrease in all the rhinitis scores was found outside the flowering
      period. There were no relevant differences in the mean scores of the different
      domains for both occupational groups. Greenhouse employees scored higher on
      limitations in activities and much lower on emotional, sleeping, and practical
      problems compared with individuals with perennial rhinitis. CONCLUSIONS: Bell
      pepper greenhouse employees are impaired in QoL because of their sensitization to
      bell pepper pollen, suggesting that bell pepper pollen is the most important
      occupational allergen in greenhouse workers with allergic symptoms. A common
      allergy does not have more impact on a person's day-to-day life than an
      occupational allergy; however, there is a clear difference in the way in which an
      occupational group is hampered compared with a nonoccupational group.

PMID- 16440541
TI  - Adhesion molecules and their ligands in nasal polyps of aspirin-hypersensitive
      patients.
AB  - BACKGROUND: Chronic inflammation with tissue eosinophilia plays a key role in the
      pathogenesis of asthma and nasal polyps in patients with aspirin
      hypersensitivity. OBJECTIVE: To evaluate the expression of vascular cell adhesion
      molecule 1 (VCAM-1) and intercellular adhesion molecule I (ICAM-1) and their
      ligands (the integrins lymphocyte function-associated antigen 1 and very late
      activation antigen 4 [VLA-4]) in nasal polyps of patients with aspirin
      hypersensitivity compared with aspirin-tolerant individuals. METHODS:
      Immunohistochemical studies were performed using a peroxidase method and
      monoclonal antibodies on 6-microm-thick cryostat sections cut from frozen polyps
      collected during elective surgery from 21 aspirin-sensitive and 23 aspirin
      tolerant patients. RESULTS: The mean +/- SD values of the semiquantitatively
      evaluated immunoexpression of ICAM-1, VCAM-1, and VLA-4 were significantly
      increased in patients with aspirin hypersensitivity compared with aspirin
      tolerant patients (1.7 +/- 0.8 vs 0.9 +/- 0.8, P < .003; 1.8 +/- 0.8 vs 0.8 +/-
      0.8, P < .001; and 2.2 +/- 0.7 vs 1.3 +/- 0.7, P < .001, respectively), whereas
      the mean +/- SD values of the expression of lymphocyte function-associated
      antigen 1 did not differ significantly (2.4 +/- 0.5 vs 2.2 +/- 0.9; P = .57). We
      found a correlation between the immunoexpression of VCAM-1 and its ligand VLA-4
      in all studied tissue samples (r = 0.4; P < .02). CONCLUSIONS: In nasal polyps of
      aspirin-hypersensitive patients, up-regulation of the adhesion molecules ICAM-1
      and VCAM-1 and the integrin VLA-4 may play an important role in the development
      of chronic eosinophilic inflammation.

PMID- 16440540
TI  - A clinical study of hypersensitivity pneumonitis presumably caused by feather
      duvets.
AB  - BACKGROUND: Bird fancier's lung (BFL) is a type of hypersensitivity pneumonitis
      induced by the inhalation of bird-related antigens. The BFL induced by feathers
      is difficult to diagnose because feathers are generally unrecognized as a
      causative antigen. OBJECTIVE: To determine the clinical features of BFL
      presumably induced by feather duvets (feather duvet lung) to provide clues for
      diagnosis. METHODS: We performed a retrospective review of the medical records of
      patients with feather duvet lung evaluated between April 1, 2000, and June 30,
      2003, at the Tokyo Medical and Dental University Hospital in Japan. RESULTS:
      Seven patients with feather duvet lung were included in this study; 4 patients
      had acute disease and 3 had chronic BFL. Duration of contact with feather duvets
      was 1 month to 10 years. Serum KL-6 and surfactant protein D levels were elevated
      in all the patients. Specific antibodies against avian antigens were positive in
      acute BFL but negative in chronic BFL. Antigen-induced lymphocyte proliferation
      in peripheral blood or bronchoalveolar lavage cells was positive in all the
      patients. The diagnosis was confirmed by an environmental or inhalation
      provocation test. CONCLUSIONS: Feather duvets can induce acute and chronic BFL.
      Physicians should be aware of feather duvets as a cause of BFL because feather
      duvets are becoming more prevalent.

PMID- 16440542
TI  - Inlet patch of gastric mucosa in upper esophagus causing chronic cough and vocal
      cord dysfunction.
AB  - BACKGROUND: An inlet patch of gastric mucosa in the upper esophagus is usually an
      incidental, congenital finding found during upper gastrointestinal tract
      endoscopy. Although it has been reported to cause dysphagia, strictures,
      adenocarcinoma, and webs, it has never been associated with cough and vocal cord
      dysfunction. OBJECTIVE: To report the first case of a patient with an inlet patch
      of gastric mucosa in the upper esophagus as the cause of a particularly
      troublesome, chronic cough that was initially missed on 2 upper endoscopies.
      METHODS: The patient is a 50-year-old man with a 7-year history of chronic cough
      associated with hoarseness, shortness of breath, and globus sensation. For
      diagnostic evaluation, pulmonary function tests, chest computed tomography,
      rhinolaryngoscopy, upper gastrointestinal tract endoscopy, and histologic
      examinations were performed. RESULTS: A multidisciplinary approach revealed
      several possible causes for the chronic cough, including vocal cord dysfunction,
      postnasal drip syndrome, allergic rhinitis, and mild gastroesophageal reflux
      disease that was only partially responsive to therapy. The results of 2 initial
      upper gastrointestinal tract endoscopies were interpreted as normal. A third
      endoscopy detected an inlet patch of gastric mucosa in the upper esophagus.
      Treatment with a high-dose histamine type 2 receptor antagonist and a proton pump
      inhibitor alleviated the patient's symptoms. CONCLUSIONS: An inlet patch of
      gastric mucosa in the upper esophagus is not uncommon, but it is often overlooked
      or believed to be an incidental, congenital finding. This is the first report, to
      our knowledge, of an inlet patch resulting in a troublesome, chronic cough.

PMID- 16440543
TI  - Necrotizing pneumonia with a questionable lung mass in a 59-year-old man.

PMID- 16440544
TI  - Allergy to lipid transfer proteins: cross-reactivity among pomegranate, hazelnut,
      and peanut.

PMID- 16440545
TI  - Importance of sensitization to Tyrophagus putrescentiae in the United States.

PMID- 16440546
TI  - Regulating to meet new demands.

PMID- 16440547
TI  - Back to the basics.

PMID- 16440548
TI  - The business of nursing.

PMID- 16440550
TI  - Influenza vaccine.

PMID- 16440549
TI  - Students appreciate RNs.

PMID- 16440551
TI  - System must be broken.

PMID- 16440552
TI  - Nurse Practitioners break new ground in British Columbia.

PMID- 16440553
TI  - Accidental exposure guidelines: what you should know.

PMID- 16440554
TI  - Professional development continues to be a challenge for many registrants.

PMID- 16440555
TI  - Using pre-printed orders.

PMID- 16440556
TI  - Sedative and psychotropic medications.

PMID- 16440557
TI  - With change comes your opportunity for input.

PMID- 16440558
TI  - [Congenital myotonic dystrophy--the significance of a handshake].
AB  - Three neonates, all girls, were presented immediately after birth with severe
      hypotonia. Two of them needed artificial ventilation because of respiratory
      insufficiency. All three pregnancies had been complicated by reduced fetal
      movements and moderate cerebral ventricular dilatation and in two of the three
      there was also polyhydramnios and congenital talipes. In all three infants
      congenital myotonic dystrophy was suspected after diagnosing myotonia in the
      mother. This was done by observing that none of the mothers were unable to
      release their grip immediately on command after shaking hands. Ophthalmological
      examination of the women revealed polychromatic lens crystals characteristic of
      myotonic dystrophy. Congenital myotonic dystrophy was confirmed by DNA analysis,
      as well as myotonic dystrophy in the mothers. All had an expansion of the number
      of cytosine-thymine-guanine(CTG)-trinucleotides in a part of the myotonic
      dystrophy protein-kinase gene. The first two infants died after 2 days and 15
      months respectively.

PMID- 16440559
TI  - [Uncertainties about the benefit of treatment in subclinical thyroid
      dysfunction].
AB  - The Leiden 85-plus study in the oldest old has observed (a) no relationship
      between thyroid function and symptoms of depression, cognitive impairment or
      disabilities in daily life, and (b) increased mortality in subjects with TSH <
      0.3 mU/l as well as longer survival in subjects with TSH > 4.8 mU/l. Subclinical
      hyperthyroidism probably warrants more proactive treatment as other studies have
      also shown increased mortality to accompany a low TSH, although no randomised
      trials have been done to prove that early intervention prevents atrial
      fibrillation or prolongs life. The benefits of treatment for subclinical
      hypothyroidism at a very advanced age are uncertain, but treatment might well be
      beneficial in middle-aged subjects as some studies report an increased risk of
      cardiovascular morbidity and mortality. In all cases, however, it is recommended
      that underlying thyroid disease be demonstrated before treatment is started.

PMID- 16440560
TI  - [Body dysmorphic disorder: insufficiently recognized].
AB  - Body dysmorphic disorder (BDD) is the current name for a psychiatric disorder
      that has been known for a long time. Patients are preoccupied with an imagined
      defect in external appearance and seek non-psychiatric treatment such as surgery,
      which leaves the underlying BDD unrecognised. Because effective psychiatric
      treatment is available, i.e. by means of selective serotonin-reuptake inhibitors
      and cognitive psychotherapy, screening for BDD in medical settings is of great
      importance.

PMID- 16440561
TI  - [Allergic rhinitis and asthma: pathophysiological relationship and implications
      for treatment].
AB  - Allergic rhinitis and asthma share various clinical, pathophysiological and
      immunological characteristics and often coexist. Recent studies provide evidence
      of cross-talk between both airway compartments, possibly by systemic signalling.
      These observations resulted in the concept of 'allergic airway disease',
      providing a rationale for systemic treatment. Presently, many novel systemic
      treatment modalities, including anti-IgE and phosphodiesterase-4 (PDE4)
      inhibitors, are being evaluated in clinical trials. In the Netherlands, there are
      currently two registered systemic therapies targeting the pathophysiological
      mechanisms of the united airway disease: leukotriene receptor antagonists and
      immunotherapy. These therapies are usually prescribed in combination with the
      standard pharmacotherapy.

PMID- 16440562
TI  - [The practice guideline 'Carcinoma of the oral cavity and oropharynx'].
AB  - With a total incidence of ca. 800 per year, oral cavity or oropharyngeal
      carcinoma represents only a small fraction of the total number of cases of cancer
      in The Netherlands. In order to achieve as much nationwide uniformity as possible
      in its diagnosis, treatment, after-care and follow-up, a practice guideline has
      now been developed. The diagnosis of the primary tumour and the neck, careful
      clinical examination is complemented by echography, often combined with a biopsy,
      MRI and CT, while technetium scintigraphy in combination with an orthopantomogram
      is used to detect invasion of the mandible. The smaller oropharyngeal carcinomas
      (T1 and T2), surgery and radiotherapy (external therapy or brachytherapy) are
      equally useful, but for the larger carcinomas (T3 and T4) in patients in good
      general condition, surgery in combination with radiotherapy is preferred. When
      radiotherapy is chosen, then brachytherapy is preferred for the smaller tumours
      of the tongue and the floor of the mouth. In patients without demonstrable
      metastases to the lymph nodes, just as in the case oforopharyngeal carcinomas,
      the decision whether or not to treat the neck depends on the chances that
      cervical lymph node metastases are present: when the risk is smaller than 20% (as
      with smaller tumours), then a wait-and-see policy is justified, but if the risk
      is greater than 20% (as with larger tumours or very thick rumours), then the neck
      should be treated, either surgically or by radiotherapy. The practice guideline
      also contains information regarding decision making, information and
      communication, palliative therapy and symptomatic treatment, psychosocial
      assistance, prosthetic reconstruction, physiotherapy, oral hygiene, nutrition and
      dietetics, swallowing and speech rehabilitation, and the policy with regard to
      smoking and alcohol consumption.

PMID- 16440563
TI  - [Diagnostic imaging (257). A boy with a swollen inguinal gland].
AB  - In a 4-year-old boy with left-sided inguinal lymphadenopathy and a papule on his
      left lower leg situated at the end of a scar of a probable cat scratch, cat
      scratch disease was confirmed serologically.

PMID- 16440564
TI  - [Thyroid function, activities of daily living and survival in extreme old age:
      the 'Leiden 85-plus Study'].
AB  - OBJECTIVE: To determine the relationship between differences in thyroid function,
      changes in the activities of daily living and survival in the extremely-old
      segment of the general population in order to see whether screening for and
      treatment of subclinical thyroid-function disorders in the elderly will have a
      positive effect. DESIGN: Prospective observational population study among 85-year
      olds. METHOD: As part of the 'Leiden 85-plus Study', all persons were followed
      who had their 85th birthday during the period from 1 September 1997 to 31 August
      1999 (average length of time followed: 3.7 years; SD: 1.4). There were 558
      participants. The thyroid function of these subjects was determined and the
      limitations in the activities of daily living, depressive symptoms, cognitive
      function and mortality were recorded annually. RESULTS: At the age of 85, there
      was no relation between the serum levels of thyroid-stimulating hormone (TSH) or
      free thyroxine (FT4) and limitations in the activities of daily living, the
      occurrence of depressive symptoms and cognitive deterioration. Neither was any
      relationship found during the period of follow-up. A higher TSH-level was
      associated with a lower mortality, even after correction for the differences in
      performance and health during the base measurement (mortality risk: 0.77 per SD
      increase in TSH; 95% CI: 0.63-0.94). The mortality risk per SD-increase in FT4
      was 1.16 (95% CI: 1.04-1.30). CONCLUSION: From the age of 85, there was no
      relationship between thyroid function and limitations in the activities of daily
      living, the occurrence of depressive symptoms or a deterioration in cognitive
      functions. Moreover, elderly persons with a less active thyroid gland lived
      longer. This raises the question whether the screening for and treatment of
      subclinical thyroid-function disorders in persons of extreme old age, as
      recommended, will have any positive effects.

PMID- 16440565
TI  - [Body dysmorphic disorder in 3-8% of patients in outpatient dermatology and
      plastic surgery clinics].
AB  - OBJECTIVE: To determine the 6-month prevalence of body dysmorphic disorder (BDD)
      in outpatient clinics of dermatology and plastic surgery in a university medical
      centre. DESIGN: Questionnaire study. METHOD: In the period January 2004-June
      2004, the self-reported Body dysmorphic disorder questionnaire was completed by
      530 and 475 new patients in the outpatient clinics of dermatology and plastic
      surgery, respectively. The dermatologist or plastic surgeon assessed the severity
      of the defect. To meet the DSM-IV criteria for BDD, the patient must have been
      preoccupied with treatment of all or part of their appearance, experienced
      obvious suffering or restriction of function with minimal or no defect present
      (defect score 1 or 2). RESULTS: In the outpatient clinics ofdermatology and
      plastic surgery 8.5% (95% CI: 6.1-10.9) and 3.2% (95% CI: 1.7-4.7) of patients
      screened positive for BDD, respectively. CONCLUSION: A high prevalence of BDD was
      found in the outpatient clinics ofdermatology and plastic surgery. Because
      dermatologists and plastic surgeons do not often recognise BDD, a simple
      screening tool is needed.

PMID- 16440566
TI  - [Possible teratogenic effects of thiamazole].
AB  - A newborn male presented with choanal atresia and minor dysmorphic facial
      features. At 4 years of age he showed delayed speech and language development.
      His mother had been treated with thiamazole for pre-existing hyperthyroidism
      during the first 3 months of pregnancy. It is possible that the maternal use of
      thiamazole caused the congenital anomalies. Embryopathy caused by maternal
      thiamazole use during pregnancy has been described several times before and is
      mainly characterised by choanal atresia, oesophageal atresia, minor dysmorphic
      facial features, growth retardation and delayed psychomotor development. Because
      the use of propylthiouracil during pregnancy has not been associated with similar
      effects, it is the treatment of choice for hyperthyroidism during pregnancy. For
      pregnant women or women who wish to become pregnant, thiamazole should be
      prescribed only ifpropylthiouracil cannot be used.

PMID- 16440567
TI  - [Neonatal infection with Listeria monocytogenes: rare, but serious].
AB  - Between 1993 and 2003, three infants, two girls and a boy, were found to have an
      invasive infection with Listeria monocytogenes. They received intensive care
      including respiratory and circulatory support, antibiotics, and treatment of the
      neurological complications when possible. One of the girls survived without
      sequelae but the other two infants died in the neonatal period. In one of these
      two cases there was a clear clue to the source of the infection in the dietary
      history of the mother: she had consumed unpasteurised cow's milk. The mothers
      ofthe infants that died had developed fever shortly before parturition. In The
      Netherlands, the incidence of neonatal invasive infection with Listeria is
      estimated at 1.3 per 100,000 live-born children per year. This figure seems not
      to have changed in the last 20 years. Because of the risk of this rare but
      serious infection, dietary advice to pregnant women to avoid possibly
      contaminated food is still relevant.

PMID- 16440568
TI  - Carotid artery stenting with protection device. Point of view of the
      interventional (neuro-) radiologist.

PMID- 16440569
TI  - Multidetector-row CT of renal arteries: review of the performances in normo- and
      hypertensive patients.
AB  - OBJECTIVE: To justify and illustrate the advantages of multidetector-row CT
      (MDCT) as probably the most effective method for imaging of renal arteries and to
      debate the question of multiple renal arteries. METHODS AND MATERIAL: The renal
      arteries of 158 hypertensive patients were investigated with 8-row and 16-row
      MDCT using a highly standardized protocol; the results were compared with those
      obtained in a group of 112 normotensive patients. RESULTS: MDCT of the renal
      arteries was found technically safely interpretable in 97.4% of cases.
      Fibromuscular dysplasia was found in 7/156 hypertensive patients (4.66%)
      concerning 9 arteries (2.18%) and > 50% atherosclerotic stenosis (in term of
      reduction of the cross-sectional area) was found in 11/156 patients (7%)
      concerning 14 arteries (3.4%). Accessory renal arteries were found in 66/156
      hypertensive patients (42.3%) implicating 84 kidneys (27%) and in 50/112 patients
      (44.6%) of the normotensive group implicating 67 kidneys (29.9%). CONCLUSION:
      With a good protocol, MDCT of the renal arteries is technically interpretable in
      most patients and can safely rule out atherosclerotic stenosis and/or
      fibromuscular dysplasia. The systematic cine-review of the native millimetric
      reconstructions and volume rendering images are the most recommended methods.
      Direct axial MPR views of the arterial lumen are also possible permitting a
      precise calculation of the percentage of stenosis from the cross-sectional area
      of the artery, an advantage on DSA in cases of asymmetrical stenosis. Finally a
      very high prevalence of multiple renal arteries--the highest ever reported to our
      knowledge--is found and the prevalence appears similar in both hypertensive and
      normotensive groups; this high prevalence not only confirms and emphasises the
      very high sensibility and resolution of MDCT but also definitively disproves the
      hypothesis that multiple renal arteries could predispose to hypertension.

PMID- 16440570
TI  - Lumbar plexus involvement with chronic inflammatory demyelinating polyneuropathy
      (CIDP): a variant case of the generic disorder.
AB  - We report the magnetic resonance (MR) findings in a male patient presenting with
      a variant chronic idiopathic demyelinating polyneuropathy (CIDP). He developed a
      slowly progressive weakness of the right leg associated with sensory dysfunction.
      Electrophysiologic studies were pathognomonic for a lower limb demyelinating
      polyneuropathy based on the slowed conduction velocities of the nerves. MRI
      showed the two major features of the disease: marked asymmetric enlargement of
      the lumbar plexus nerve roots and strong hypersignal of the enlarged roots on
      STIR images.

PMID- 16440571
TI  - Skull base chordoma: CT and MRI features.
AB  - We report the case of a 10-year-old boy who presented an intracranial chordoma
      and we stress the importance of sectional imaging to approach the diagnosis.
      Clinical presentation is related to local invasion. Lesion of the body of the
      clivus can extend ventrally or dorsally and cause cranial nerve palsies, brain
      stem compression or hydrocephalus. Pathologically, they form soft, grey masses
      that are histologically benign but locally invasive and destructive. Both
      computed tomography (CT) and magnetic resonance (MR) imaging clearly depict the
      lesion. CT better demonstrates bone destruction and intralesional calcifications.
      In our case, MR was performed first and showed all the classical signs of skull
      base chordoma. CT provided complementary information about bone destruction which
      are also usual in this type of lesion. Major differential diagnoses of the
      chordoma in the clivus are the other central skull base masses. Biopsy and
      histology make the diagnosis. Usually treatment consists in surgery and
      radiotherapy but more recently proton beam therapy is used and seems to yield
      better results.

PMID- 16440572
TI  - Incidental sonographic finding of an extracranial internal carotid artery
      aneurysm confirmed by CT angiography.
AB  - We report a rare case of an extracranial internal carotid artery aneurysm (EICAA)
      discovered incidentally by color Doppler sonography (CDUS) and confirmed by CT
      angiography with three-dimensional reconstructions. As both brain MRI and
      cerebral angiography were normal and the patient remained asymptomatic, he was
      neither operated on nor stented but was discharged with appropriate antiplatelet
      therapy. The volume of his EICAA is checked regularly by CDUS.

PMID- 16440573
TI  - Bone marrow changes in sports injuries.
AB  - This paper will briefly discuss the value of MRI in the detection and follow-up
      of bone marrow edema resulting from acute and chronic trauma in sports injuries.
      A meticulous pattern approach of the distribution of bone marrow changes around a
      joint can reveal in most instances the underlying mechanism of trauma. The use of
      fatsuppressed T2-weighted or STIR images is most appropriate to detect bone
      marrow edema.

PMID- 16440575
TI  - Inverted solitary fibrous tumor of the pleura mimicking a pulmonary mass.

PMID- 16440574
TI  - Whole-body magnetic resonance imaging: technical aspects, indications and
      preliminary experience.
AB  - This article reviews the interest and potential applications of whole body MR and
      presents a new technical concept of the technique. Preliminary experience with
      this new technology is presented.

PMID- 16440576
TI  - Extramedullary plasmacytoma of the sphenoid sinus.

PMID- 16440577
TI  - Topical tacrolimus in Hailey-Hailey disease.
AB  - Hailey-Hailey disease, or familial benign chronic pemphigus, is a rare relapsing
      remitting autosomal-dominant epidermal blistering disease. It preferentially
      affects females and is characterized by recurrent vesicles and erosions in the
      intertriginous areas. There are several topical corticosteroid therapeutic
      options, which are often limited in their use by their secondary effects and
      localization of the lesions. We report a case of a 60-year-old woman with Hailey
      Hailey disease involving axillary, groin, cervical, antecubital, inframammary and
      abdominal folds. She was treated with 0.1% tacrolimus ointment, applied twice
      daily, with clinical improvement in 2 weeks and total remission in 4 weeks. She
      remains asymptomatic after a 10-month follow-up period.

PMID- 16440578
TI  - Psoriasis vulgaris: once-versus twice-daily application of calcipotriol cream.
AB  - The cause of psoriasis is still unknown. It occurs with equal frequency in both
      sexes. In many patients topical application alone will suffice to keep psoriasis
      under control. Vitamin D3 affects keratinocyte differentiation in psoiasis.
      Thirteen patients with mild to moderate psoriasis vulgaris were enrolled in this
      trial (eight men and five women), aged between 14 and 40 years. Each patient was
      instructed to apply calcipotriol cream once daily on the right side and twice
      daily on the left side for 6 weeks. The treatment assessment was based on
      psoriasis area severity index (PASI) at 0, 2, 4 and 6 weeks. Serum calcium was
      assessed prior to and at the end of treatment. Calcipotriol cream was clearly
      effective in psoriasis and in both sides an almost similar effect was seen. The
      reduction in PASI was remarkable in both sides and the change was from 7.9
      (pretreatment) to 2.4 (once daily) and 2.1 (twice daily). Out of the treated
      patients, seven (53.8%) had complete to marked clearance of both sides. Two
      patients (once daily) versus three patients (twice) had moderate improvement.
      Mild improvement was observed in three with twice-daily and in two with once
      daily application. Post-treatment serum calcium was normal in all cases. In
      conclusion, there was no significant difference between once- and twice-daily
      application of calcipotriol cream, and single night application of topical
      calcipotriol could be more practical and reliable, and less expensive.

PMID- 16440579
TI  - Ultrasonography in the early diagnosis of psoriasis-associated enthesopathy.
AB  - The aim of the present study was to detect entheseal abnormalities by means of
      ultrasonography (US) in patients with psoriasis. We evaluated 24 patients with
      psoriasis who underwent clinical and ultrasonographic examination of both lower
      limbs at the calcaneal insertions of the Achilles tendons and at the flexor and
      extensor tendons of all fingers of the hand. Fourteen patients with psoriatic
      arthritis were used as controls. US was performed using a real-time scanner (ATL
      SDI 3000) with a 5-12 MHz linear array transducer. Longitudinal and transverse
      scans of the talocrural joints, Achilles tendons and both the flexor and extensor
      tendons of the fingers of both hands were obtained at rest and during active and
      passive movements. On clinical examination no entheseal site was abnormal, but on
      US examination 33% of patients showed abnormalities. In particular, six psoriasis
      patients (25%) who were asymptomatic showed effusion around the extensor tendon
      of the first digit of the left hand and around the extensor tendon of the third
      and fourth digits of both hands; two patients (8.3%) showed a hypoechoic nodular
      formation of the flexor tendon sheath of the left hand. We conclude that
      entheseal abnormalities not detected at clinical examination were present in 33%
      of patients with psoriasis who underwent US examination. Therefore, we suggest
      the routine use of ultrasonography in the early diagnosis and in treatment and
      follow-up of patients with tendon enthesopathy, since these factors may have
      implications for therapy.

PMID- 16440580
TI  - Calcipotriol solution in scalp psoriasis.
AB  - Psoriasis is characterized by three main pathogenic features: abnormal
      differentiation, keratinocyte hyperproliferation and inflammation. The lesions
      may disappear spontaneously or as a result of therapy, but recurrences are almost
      certain. Twenty-seven patients with scalp psoriasis were treated with
      calcipotriol solution 50 g/ml as twice-daily application for 8 weeks. The
      assessment was based on the mean sign scores (erythema, thickness and scaliness)
      at 0, 2, 4, 6 and 8 weeks. The results indicated that five patients were excluded
      from the study (four because of irregularity and one because of irritation), and
      22 patients had completed the treatment course. There was a marked reduction in
      the total mean scores of erythema, thickness and scaling from 2.8, 2.7 and 2.7 to
      0.3, 0.34 and 0.4, respectively. Fifteen patients (68.2%) showed complete
      clearance of their psoriasis, and most of the lesions cleared by week 6 of
      treatment. Two patients (9.1%) had marked improvement and four (18.2%) patients
      showed moderate improvement. No response to calcipotriol solution was seen in
      only one patient. No adverse effects occurred except severe irritation in one
      patient, who was excluded from this study. In conclusion, calcipotriol could be a
      valid choice for the treatment of scalp psoriasis.

PMID- 16440581
TI  - Efficacy of imiquimod in solitary plaques of mycosis fungoides.
AB  - Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. The
      extent and type of skin involvement (T classification) and presence of lymph node
      or visceral involvement are important predictors in selecting the type of
      treatment. Skin directed treatment represents the most appropriate therapy for
      early stage disease. Current topical treatment including potent topical steroids
      and nitrogen mustard are associated with adverse effects such as cutaneous
      atrophy and contact dermatitis. In the present study, we tested the efficacy of
      imiquimod in mycosis fungoides plaques.

PMID- 16440582
TI  - Increasing incidence of melanoma in central Greece: a retrospective
      epidemiological study.
AB  - The increasing incidence of melanoma in the general population during the last
      few decades has provoked a great deal of research, aiming to identify the
      possible relationship between old and new etiological factors involved in the
      pathogenesis of this tumor. The aim of the study was to evaluate the incidence of
      melanoma in central Greece, especially in the prefecture of Larissa from January
      1988 to December 1998. Data were collected from the General Hospital of Larissa.
      Seventy-one cases of melanoma were studied (41 females, 30 males). The incidence
      increased from 1.36/100,000 patients during the first year of the study (1988) to
      5.2/100,000 patients in the last year of the study (1998). The patients'skin
      types were: type 12.8%, type II 52.1%, type III 45.1%. The median age of patients
      was 61.9 years, 61.4 years in female and 62.5 years in male patients. Concerning
      their occupation, farmers accounted for 56.3%. Melanomas were most frequently
      located on head and neck (36.6%), extremities (30.98%) and trunk (11.3%).
      Superficial spreading melanomas were observed in 44% of the patients and nodular
      melanomas in 20%. In conclusion. there was a rapid increase in the incidence of
      melanoma in our region especially during the last 3 years.

PMID- 16440583
TI  - Tissue reaction at the implantation of recombinant human bone morphogenetic
      protein-2 into the skeletal muscle.
AB  - Bone morphogenetic protein (BMP) is a unique cytokine that induces bony tissue in
      soft tissue. Tissue reactions at and around the implantation of recombinant human
      BMP-2 (rhBMP-2) into the soft tissue of rats and nonhuman primates were
      investigated. At the osteoinduced site of rats, massive trabeculae-lined
      osteoblasts and rich marrow were observed. At and around the nonosteoinduced
      sites of nonhuman primates, large clear nuclei were observed in reaction to rhBMP
      2 implantation. The surrounding area was visually classified into zones 1, 2 and
      3. Zone 3 was near the center of the implant. The area of nuclei, the major axis,
      the minor axis and the ratio of minor axis per major axis were image-analyzed in
      the histological views. In zones 1, 2 and 3, the nuclear areas were 18.0 (3.1)
      mean (SD); unit micron2, 33.4 (5.61) and 110.1 (23.7), respectively. The major
      axes of nuclear ellipses were 7.45 (0.22) (unit micron), 7.76 (0.26), and 13.9
      (1.88), respectively. The minor axes were 3.07 (0.53), 5.59 (0.95) and 10.1
      (1.35), respectively. The ratios of minor axis per major axis of nuclear ellipses
      were 0.4 (0.57), 0.72 (0.11) and 0.73 (0.11) in zones 1, 2 and 3, respectively.
      These results showed that in zones 2 and 3 cell and tissue reactions were marked
      against rhBMP-2 implantation.

PMID- 16440584
TI  - Minodronate, a nitrogen-containing bisphosphonate, inhibits advanced glycation
      end product-induced vascular cell adhesion molecule-1 expression in endothelial
      cells by suppressing reactive oxygen species generation.
AB  - Advanced glycation end products (AGEs), the senescent macroprotein derivatives
      that form in increased amounts in diabetes, have been implicated in the
      pathogenesis of diabetic vascular complications. Indeed, AGEs elicit oxidative
      stress generation in vascular wall cells through an interaction with their
      receptor (RAGE), thus playing an important role in vascular inflammation and
      altered gene expression of growth factors and cytokines. We have previously shown
      that minodronate, a nitrogen-containing bisphosphonate, blocked the angiogenic
      signaling of vascular endothelial growth factor in ECs through its antioxidative
      properties. However, the effects of minodronate on AGE-exposed ECs remain to be
      elucidated. In this study, we investigated whether and how minodronate could
      inhibit AGE-induced reactive oxygen species (ROS) generation and subsequent
      vascular cell adhesion molecule-1 (VCAM-1) gene expression in human umbilical
      vein endothelial cells (HUVEC). Minodronate or an NADPH oxidase inhibitor,
      diphenylene iodonium, completely inhibited the AGE-induced ROS generation in
      HUVEC. Geranylgeranyl pyrophosphate reversed the antioxidative properties of
      minodronate in AGE-exposed ECs. Furthermore, minodronate was found to prevent AGE
      induced nuclear factor--KB activation and subsequently suppress VCAM-1 gene
      expression in HUVEC. These results demonstrate that minodronate could inhibit
      VCAM- 1 expression in AGE-exposed ECs by suppressing NADPH oxidase-derived ROS
      generation, probably via inhibition of geranylgeranylation of Rac, a component of
      endothelial NADPH oxidase. Our present study suggests that minodronate may have a
      therapeutic potential in the treatment of patients with diabetic vascular
      complications.

PMID- 16440585
TI  - Pigment epithelium-derived factor is a pericyte mitogen secreted by microvascular
      endothelial cells: possible participation of angiotensin II-elicited PEDF
      downregulation in diabetic retinopathy.
AB  - Pigment epithelium-derived factor (PEDF) is a natural extracellular component of
      the retina with neuronal differentiating activity. Decreased levels of PEDF in
      the mammalian eye have been shown to participate in proliferative diabetic
      retinopathy. In addition, we have recently found in in vitro experiments that
      PEDF protected against pericyte apoptosis, the earliest histopathological
      hallmark of diabetic retinopathy. These observations suggest that the loss of
      PEDF in the mammalian eye plays an important role in the development and
      progression of diabetic retinopathy. However, the functional role of endothelial
      cell (EC)-derived PEDF in pericyte survival and the regulation of PEDF gene
      expression remain to be elucidated. In this study, we examined the effects of
      anti-PEDF antibody (Ab) on the viable cell number of cocultured pericytes with
      microvascular ECs. We further studied the effects of angiotensin II (Ang II) on
      PEDF gene expression in ECs. Anti-PEDF Ab significantly inhibited the growth
      stimulating effects of cocultured ECs on pericytes. Furthermore, Ang II
      significantly decreased PEDF mRNA levels in ECs, which was completely reversed by
      an Ang II type 1 receptor blocker, telmisartan. Our present results suggest that
      PEDF is an EC-derived mitogen or survival factor for retinal pericytes.
      Suppression by Ang II of the EC-derived PEDF may be involved in exacerbation of
      diabetic retinopathy in patients with hypertension.

PMID- 16440586
TI  - Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological
      changes of prostate hyperplasia induced with testosterone in rats.
AB  - Benign prostatic hyperplasia (BPH) is the nonmalignant, uncontrolled growth of
      prostate gland cells and stroma leading to difficulty in urinating. Lipid
      extracts from Saw palmetto (Arecaceae) fruits are used to treat BPH. The Cuban
      royal palm (Roystonea regia) is a member of this family and D-004, a lipid
      extract from its fruits, prevents prostate hyperplasia (PH) induced with
      testosterone, as opposed to dihydrotestosterone, in rodents. This study
      investigated whether D-004 could prevent the histological features of
      testosterone-induced PH in rats. Rats were distributed into six groups (10 rats
      per group): A negative control group receiving subcutaneous injections of soy oil
      and treated with vehicle, and five groups injected subcutaneously with
      testosterone and treated with the vehicle (positive control), D-004 (100, 200 and
      400 mg/kg) or Saw palmetto (400 mg/kg). Treatments were given orally for 14 days.
      At sacrifice, prostates were removed and processed for light microscopy. The
      histopathological findings of PH were assessed according to a score-chart
      protocol. D-004 200 and 400 mg/kg, but not 100 mg/kg, significantly and
      moderately in a dose-dependent manner prevented prostate enlargement and the
      testosterone-induced histological changes. Compared with positive controls, D-004
      200 and 400 mg/kg inhibited prostate size increases and the histological score up
      to 56.1% and 60.7%, respectively, while Saw palmetto 400 mg/kg reduced such
      variables by 45.8% and 49.0%, respectively. The effects of D-004 400 mg/kg on the
      histological changes, not on prostate size, were greater (p < 0.05) than those of
      Saw palmetto. D-004 and Saw palmetto did not affect body weight values. In
      conclusion, D-004 200 and 400 mg/kg administered orally for 14 days prevented the
      increase of prostate size and the testosterone-induced histological changes in
      rats, its effects being comparable or mildly better than those of Saw palmetto.
      These results extend previous data showing preventive effects of D-004 on
      testosterone-induced prostate enlargement with in rodents, and further studies
      are required to explore the mechanisms underlying such effects.

PMID- 16440587
TI  - Effects of D-003 (5-200 mg/kg), a mixture of high molecular weight aliphatic
      acids from sugarcane wax, on bones and bone cell apoptosis in ovariectomized
      rats.
AB  - The mevalonate pathway is crucial for osteoclast function. D-003 is a mixture of
      high molecular weight acids purified from sugarcane wax, which inhibits
      cholesterol biosynthesis through HMG-CoA reductase regulation. D-003 administered
      at 50 and 200 mg/kg for 12 weeks prevented bone loss in ovariectomized rats,
      increasing osteoclast apoptosis. The present study investigated whether the
      effects of D-003 on bone resorption and osteoclast apoptosis are dose-dependent.
      Rats were randomized into seven groups (10 rats/group): two control groups orally
      treated with the vehicle, one false-operated (sham) and another ovariectomized
      group (positive control), while another four groups received D-003 (5, 25, 50 and
      200 mg/kg). The effects on bone resorption and formation were studied through
      histomorphometry and the effects on apoptosis through immunohistochemistry. D-003
      (5-200 mg/kg) dose-dependently and significantly prevented (p < 0.001) changes in
      trabecular bone and increase in osteoclast surface and number versus
      ovariectomized controls, leaving osteoblast surfaces unchanged. Across the dose
      range, D-003 significantly increased (p < 0.05) osteoclast apoptosis in a dose
      dependent manner and reduced (p < 0.05) osteoblast and osteocyte apoptosis versus
      ovariectomized controls, but these effects did not show dose dependence. In
      conclusion, D-003 (5-200 mg/kg) orally administered at for 12 weeks prevented
      bone loss and bone resorption and increased osteoclast apoptosis in
      ovariectomized rats in a dose-dependent manner. These results are consistent with
      previous data, showing that D-003 administered at relatively low doses prevents
      bone loss induced with ovariectomy, which could be useful to prevent or treat
      bone loss in postmenopausal women. Further experimental and clinical studies,
      however, are needed to confirm these findings.

PMID- 16440588
TI  - Gunshot wounds.

PMID- 16440589
TI  - History of the Department of Surgery, Nelson R. Mandela School of Medicine,
      University of KwaZulu-Natal.

PMID- 16440590
TI  - Factors affecting mortality and epidemiological data in patients hospitalised
      with burns in Diyarbakir, Turkey.
AB  - BACKGROUND: Burns continue to be responsible for significant morbidity and
      mortality in developing countries. In this study we aimed to determine the
      factors affecting mortality and epidemiological data by examining the records of
      burned patients. METHOD: The hospital records of 980 patients who were
      hospitalised in the Burns Unit at Dicle University Hospital (DUH) between June
      1994 and July 1999 were examined for factors affecting mortality. Factors
      evaluated included gender, age, burn type, degree and extent of burn, prognosis
      and length of hospitalisation (LH). We investigated the relationship (if any)
      between the demographic data, degree and extent of burns and mortality and
      morbidity rates. RESULTS: The study group consisted of 325 males (33.2%) and 655
      females (66.8%). Of the patients 738 (75.3%) were children (age under 15 years),
      217 (22.1%) were younger adults (age 15-50 years), and 25 (2.6%) were older
      adults (age over 50 years). The mean age was 11.2 +/- 14.01 years (range 15 days
      95 years). Of the burns 618 (63.1%) were scalds, 199 (20.3%) burns from a flame
      and 163 (16.6%) electrical burns. The mean extent of burn was 24.3 +/- 14.5%
      (range 1-95%). Seven hundred and eighty-seven (80.3%) of the study group made a
      full recovery, 131 (13.4%) were discharged from hospital after partial recovery,
      and 62 (6.3%) died. The mean LH was 11.33 +/- 8.8 days (range 1-67 days). There
      was a positive correlation between burn extent and mortality (r = 0.35, p <
      0.0001) and between age and type of burn (r = 0.60, p < 0.0001). While scalds had
      the highest frequency among children, flame and electrical burns were most common
      in the adult and older adult groups. There was also a positive correlation
      between degree and type of burn (r = 0.32, p = 0.0001), scalds tending to be more
      superficial while flame and electrical burns were generally more serious. Deaths
      of patients with extensive burns usually occurred in the first 5 days following
      injury due to acute renal failure and hypovolaemic shock, while deaths from
      moderate and minor burns usually occurred after 7 days and were due to wound
      infection and sepsis. CONCLUSION: We found positive correlations between age and
      type of burn, degree and type of burn, and the extent of burn and mortality. The
      overall mortality rate for our unit was 6.3%.

PMID- 16440591
TI  - Gunshot injuries of the spine--a review of 49 cases managed at the Groote Schuur
      Acute Spinal Cord Injury Unit.
AB  - The Acute Spinal Injury Unit, relocated from Conradie Hospital to Groote Schuur
      Hospital in mid-2003, admitted 162 patients in the first year of its existence. A
      large number of these injuries were the result of interpersonal violence,
      particularly gunshot wounds. AIM: To review patients with gunshot injuries to the
      spine, with reference to neurological injury, associated injuries, need for
      surgery and complications. METHODS: A comprehensive database is maintained to
      collect data on all spinal injury admissions. These data, as well as case notes
      and X-rays, were reviewed for all gunshot spine patients admitted to the Acute
      Spinal Injury Unit over a year. Forty-nine patients were identified. Thirty-eight
      were male and 11 female with an average age of 27.5 years (range 15-51 +/- 8.53).
      The average stay in the acute unit was 30 (4-109 +/- 28) days. RESULTS: The
      spinal injury was complete in 38 and incomplete in 8, with 3 having no
      neurological deficit. The level was cervical in 13, thoracic in 24 and lumbar in
      12. Only 9 patients improved neurologically. The spine was considered stable in
      43 cases. Stabilisation was performed in the 6 unstable cases. The bullets were
      removed in 11 cases as they were in the canal. There were 55 significant
      associated injuries, viz. 14 haemo-pneumothoraces, 16 abdominal visceral
      injuries, 3 vascular injuries, 4 injuries of the brachial plexus and 3 of the
      oesophagus, 2 tracheal injuries, 1 soft palate injury and 11 non-spinal
      fractures. Complications included 3 deaths and discitis in 3 cases, pneumonia in
      6 and pressure sores in 6. CONCLUSION: Gunshot injuries of the spine are a
      prevalent and resource-intensive cause of paralysis. There is a high incidence of
      permanent severe neurological deficit, but usually the spine remains mechanically
      stable. Most of the management revolves around the associated injuries and
      consequences of the neurological deficit.

PMID- 16440592
TI  - Pattern of civilian gunshot injuries in Irrua, Nigeria.
AB  - This retrospective review of 76 patients with gunshot wounds was undertaken to
      evaluate the pattern and outcome of civilian gunshot injuries in our region. The
      extremities were the most commonly affected site (51.5% of all gunshot wounds).
      Gunshot injuries were most common among young males in the third decade of life,
      and armed robbery was the cause of gunshot trauma in 69.7% of cases. Time from
      injury to arrival at hospital was less than 6 hours in 64.4% of cases. Wound
      exploration and debridement were the mode of treatment in the majority of cases.
      Hypovolaemia resulting from acute haemorrhage accounted for 52.9% of
      complications. The mortality rate was 5.3%. It is pertinent to observe that
      inefficient firearm control is a major factor contributing to civilian gunshot
      injuries in our region. In addition, high rates of unemployment and poverty in
      our society may be contributing to the increasing incidence of youth restiveness,
      armed robbery and associated gunshot injuries. Strong government legislation is
      required to provide adequate security for the teeming civilian population. The
      national government should embark on a poverty eradication strategy and engage
      the youth in gainful employment to reduce the incidence of youth restiveness,
      armed robbery and firearm-related violence.

PMID- 16440593
TI  - Anorectal malformations in Africa.

PMID- 16440594
TI  - Complications of endoscopic variceal therapy.

PMID- 16440595
TI  - Recurrent intestinal obstruction and anaemia--giant lipoma of the caecum.

PMID- 16440596
TI  - Influence of streptozotocin-induced diabetes on hexokinase activity of rat
      salivary glands.
AB  - The influence of diabetes on the enzyme hexokinase (HK) was examined in the
      salivary glands of rats. Diabetes was induced by an intraperitoneal injection of
      streptozotocin (60 mg/Kg body weight) in overnight fasted rats (180-200 g). The
      animals were killed 48 hours and 30 days after the induction of diabetes and the
      submandibular and parotid salivary glands extracted for use. Hyperglycemia was
      evaluated by determining the blood sugar. The area occupied by each intralobular
      component, acini, ducts, total parenchyma and stroma was measured, and no
      differences were observed compared with control. In the soluble fraction of the
      submandibular gland, no difference in the specific activity of HK was observed,
      between the diabetic and control animals, however, the activity per gland and per
      g of tissue showed lower values than control. The specific activity of the bound
      form was reduced in the diabetic gland. The results obtained for the parotid
      gland were different from the submandibular. The specific activity of both the
      soluble and bound forms were increased in the diabetic animals. The DEAE
      cellulose column chromatography of the soluble and bound forms of the enzyme from
      both glands showed a first peak appearing during the washing of the column and
      two other peaks were eluted by the gradient. Thus, three isoenzymes in the
      submandibular and parotid salivary glands for the control and diabetic rats have
      been found.

PMID- 16440597
TI  - The effect of dexamethasone on disruption of ovarian steroid levels and receptors
      in female rats.
AB  - This study was conducted to investigate if the injection of a single dose of
      dexamethasone may cause disruption of adult female rat gonadal function in terms
      of plasma and ovarian level of both androgen and estrogen, ovarian morphology,
      and changes in localization of androgen, estrogen and glucocorticoid receptors.
      Adult female Long Evans rats (n=50, 250-300 g) were used. At day 0 rats received
      subcutaneously 1 ml of saline (n=25; control group) or dexamethasone at 0.1 mg/kg
      (n=25, treated group). Rats were sacrificed in groups of five on days 10, 15, 20,
      25 and 30 after injection. Blood samples and one ovary were collected to analyze
      dexamethasone, 17beta-estradiol (E2), testosterone (T) and androstenedione (A4)
      concentrations by amplified EIA. The remaining ovary was removed and processed
      for histopathology and immunocytochemistry. Differences between individual means
      were analyzed by Pairwise t-test and Bonferroni post test to asses whether values
      presented statistical significance. Increased E2, T and A4 levels were observed
      both in plasma and ovary samples in treated group when comparing with control (p<
      0.01) at all days post-injection even when dexamethasone was undetectable.
      Ovarian morphology of treated group showed features compatible with female
      infertility. Inmmunolocalization of androgen and estrogen receptors showed that
      both were negative in treated group while controls showed highest positivity (AR
      +++, ER ++). Glucocorticoid receptor showed higher positivity in dexamethasone
      treated rats (GR ++) than in controls (GR +). Obtained results showed clear
      evidence that a single dose of dexamethasone may disrupt gonadal function in
      rats, and that possibly leads to infertility.

PMID- 16440598
TI  - Toxic effects of cadmium on GABA and taurine content in different brain areas of
      adult male rats.
AB  - This work assesses the possible changes in gamma amino butyric acid (GABA) and
      taurine content in the hypothalamus, the median eminence and striatum after the
      exposure to various doses of cadmium. Cadmium chloride (CdCl2) was administered
      in the drinking water at the doses of 5, 10, 25, 50 or 100 ppm to adult male rats
      for 1 month. In the anterior hypothalamus, taurine and GABA content decreased
      with the dose of 10 ppm of CdCl2 only. Cadmium exposure decreased both GABA and
      taurine content in mediobasal hypothalamus except for the 50 ppm dose. In
      posterior hypothalamus GABA and taurine content was not affected by cadmium
      treatment. As far as the median eminence, 5 or 10 ppm of CdCl2 increased taurine
      concentration, and at a dose of 5 ppm enhanced GABA content. A significant
      decrease of GABA and taurine concentration was seen in the striatum at any dose
      of cadmium used. The concentration of cadmium increased in the hypothalamus and
      in the striatum in animals receiving CdCl2 in the drinking water at doses of 25,
      50 or 100 ppm. The results indicate that cadmium globally decreased GABA and
      taurine content in the brain areas studied through effects that were not dose
      dependent.

PMID- 16440599
TI  - Effects of 5-hydroxydecanoate and ischemic preconditioning on the ischemic
      reperfused heart of fed and fasted rats.
AB  - This investigation aimed to assess whether the mitochondrial ATP-sensitive
      potassium channel blocker 5-hydroxydecanoate (5-HD) could abolish the protection
      conferred by fasting and ischemic preconditioning (IPC) and to ascertain whether
      these effects are associated with glycogen breakdown and glycolytic activity.
      Langendorff perfused hearts of fed and 24-h fasted rats were exposed to 25 min
      ischemia plus 30 min reperfusion. IPC was achieved by a 3 min ischemia plus a 5
      min reperfusion cycle. 5-HD (100 microM) perfusion begun 5 min before IPC or 13
      min before sustained ischemia in the non preconditioned groups. Fasting improved
      the reperfusion recovery of contraction, decreased the contracture and the
      lactate production, increased glycogenolysis and did not affect the percentage of
      viable tissue. 5-HD abolished the effects of fasting on the contractile recovery
      but did not affect the contracture. 5-HD decreased the lactate production in the
      fed group, increased the preischemic glycogen content in both nutritional groups
      and did not affect the ischemic glycogen fall. IPC improved the contractile
      function but prevented the contracture only in the fed group, reduced lactate
      accumulation and glycogenolysis and evoked an increase of the viable tissue. 5-HD
      abolished the effects of IPC on the contractile recovery and did not affect its
      effect on the contracture, lactate production, glycogenolysis and viable tissue.
      These data suggest that the mitocondrial ATP-sensitive potassium channel is
      involved in the effects of fasting and IPC on the contractile function but the
      other cardioprotective and metabolic effects appear evoked through other
      mechanisms. Also suggest that besides the inhibition of the mitochondrial
      potassium channel, other mechanisms mediate the effects of 5-HD.

PMID- 16440600
TI  - Temporal changes in renal endoglin and TGF-beta1 expression following ureteral
      obstruction in rats.
AB  - Chronic renal disease is characterized by the accumulation of extracellular
      matrix proteins in the kidney and a loss of renal function. Tubulointerstitial
      fibrosis has been reported to play an important role in the progression of
      chronic renal diseases. Transforming growth factor-beta1 (TGF-beta1) is a
      profibrotic cytokine playing a major contribution to fibrotic kidney disease.
      Endoglin is a membrane glycoprotein of the TGF-beta1 receptor system. The aim of
      this work was to determine the time-course expression of renal type I and IV
      collagens, endoglin and TGF-beta1 in a rat model of induced tubulointerstitial
      fibrosis at 1, 3, 10 and 17 days after unilateral ureteral obstruction (UUO). In
      17 days-ligated (L)-renal samples, a marked interstitial fibrosis was detected by
      Masson's trichromic and Sirius red staining, accompanied by an increase in type I
      collagen expression as shown by immunohistochemical analysis. Northern blot
      studies revealed a progressive increase in collagen alpha2(I), TGF-beta1 and
      endoglin mRNA expression in L kidneys when compared with the corresponding non
      ligated (NL) kidneys from the animals subjected to left UUO. Seventeen days after
      UUO, significant increases in collagen alpha2(I), collagen alpha1(IV), TGF-beta1
      and endoglin mRNA levels were detected in L kidneys vs NL kidneys. Significantly
      higher levels of the protein endoglin were found in L kidneys than in NL kidneys
      10 and 17 days following obstruction. A marked increase expression for endoglin
      and TGF-beta1 was localized in renal interstitium by immunohistochemical studies
      17 days after obstruction. In conclusion, this work reports the upregulation of
      endoglin coincident to that of its ligand TGF-beta1 in the kidneys of rats with
      progressive tubulointerstitial fibrosis induced by UUO.

PMID- 16440601
TI  - Complexity of the human whole saliva proteome.
AB  - Recent characterization of the whole saliva proteome led to contradictory
      pictures concerning the complexity of its proteome. In this work, 110 proteins
      were analysed by mass spectrometry allowing the identification of 10 accessions
      previously not detected on protein two-dimensional maps, including myosin heavy
      chain (fast skeletal muscle, IIA and IIB), phosphatidylethanolamine binding
      protein, secretory actin-binding protein precursor and triosephosphate isomerase.
      Further comparison with available data demonstrated simultaneously a low
      diversity in terms of variety of accessions and a high complexity in terms of
      number of protein spots identifying the same accession, the two thirds of
      identified spots corresponding to amylases, cystatins and immunoglobulins. This
      diversity may be of interest in the development of non invasive diagnostic tool
      for several disease.

PMID- 16440603
TI  - Climate change and health in the circumpolar north.

PMID- 16440604
TI  - Climate related events and community preparedness.

PMID- 16440602
TI  - Inflammation and conjugated linoleic acid: mechanisms of action and implications
      for human health.
AB  - Data from a number of studies and trials have shown that different conjugated
      linoleic acids (CLA's) may produce beneficial effects on cancer, atherosclerosis,
      hypertension, diabetes and changes in body composition. Despite the increasing
      knowledge about CLA's implications on health, the mechanism of action of these
      fatty acids is not completely understood. Moreover, human studies indicate that
      some of these beneficial effects are considerably less evident than anticipated
      from mice studies, while the efficacy and safety of dietary supplements
      containing CLA have been questioned in some intervention trials. Recently, it has
      been suggested that the anti-carcinogenic and anti-atherosclerosis effects of
      CLA's stem from its anti-inflammatory properties. Because inflammatory responses
      are associated with the pathophysiology of many diseases, including obesity and
      the metabolic syndrome, the investigation in this area is of growing interest in
      recent years.

PMID- 16440605
TI  - Monitoring as a community response for climate change and health.

PMID- 16440606
TI  - Changing living conditions, life style and health.
AB  - Human health is the result of the interaction of genetic, nutritional, socio
      cultural, economic, physical infrastructure and ecosystem factors. All of the
      individual, social, cultural and socioeconomic factors are influenced by the
      environment they are embedded in and by changes in this environment. The aim of
      the paper is to illustrate the influence of environmental change on living
      conditions and life style and some of the mechanisms through which such changes
      affect physical and mental health. The interrelationship between environmental
      and societal change is illustrated by an example from a small community in
      Greenland, where changing environmental conditions have influenced fishing and
      employment opportunities to the extent that the size of the population has
      changed dramatically. The link between social change and health is shown with
      reference to studies on education, housing and occupation as well as life style
      changes. The paper further illustrates the relationship between the rapid socio
      cultural and economic change and the health of the population. Psychosocial
      stress is reflected in problems such as alcohol abuse, violence and suicide, and
      these factors have been shown in studies on migration and transitions in health
      to be connected to changes in lifestyle and living conditions.

PMID- 16440608
TI  - Impacts of cold climate on human heat balance, performance and health in
      circumpolar areas.
AB  - In circumpolar areas the climate remains cool or thermoneutral during the
      majority of the days of the year spite of global warming. Therefore, health
      consequences related to cold exposure represent also in the future the majority
      of climate-related adverse health effects. Hot summers may be an exception. At
      ambient temperatures below +10 - +12 degrees C, humans experience cold stress of
      varying degree. Man can compensate a 10 degrees C change in ambient temperature
      by changing metabolic heat production by 30-40 W m(-2) or by wearing an
      additional/taking off ca. 0.4 clo units (corresponding to one thick clothing
      layer). Cold ambient temperature may be a risk for human health and cause varying
      levels of performance limitations. The impacts of cold exposure on health and
      wellbeing cause a burden to many societies in terms of lowered productivity and
      higher costs related to health care systems as well as public health planning and
      management. In order to provide preventive and protective public health actions
      for cold-induced adverse health effects, it is important to recognize cold
      related injuries, illnesses and symptoms and their turn-up temperatures, and to
      identify the most at-risk population subgroups and factors that increase or
      decrease the health risks posed by cold ambient temperatures. The majority of
      cold-related harmful health impacts can be prevented or managed by correct
      preventive and protective actions. Rapid unpredictable changes are more difficult
      to compensate because of lack of experience (affecting attitude and skills),
      preparedness (vehicles, garments, supplies, logistics etc.) and/or
      acclimatization.

PMID- 16440607
TI  - Environmental temperature and mortality.
AB  - In Finland, mortality increases steeply in autumn, reaches a peak during the
      Christhmas holidays and declines slowly towards a trough in August. The relative
      excess in daily mortality (peak vs. trough) is 30% for coronary heart disease,
      40% for cerebral vascular accidents and 90% for diseases of the respiratory
      organs. There is a secondary peak in Midsummer, especially in coronary deaths of
      working aged men. Mortality is lowest at mean daily temperature of +14 degrees C,
      and it increases slowly with falling temperature and steeply with increasing
      temperature. An estimated 2000-3000 extra deaths occur in Finland during the cold
      season, most of which are people aged 65 years and over but 20% at working age.
      The number of people dying from high temperatures (over +14 degrees C) in this
      country in a normal year is 100-200. Heat deaths are mostly certified as being
      due to cardiovascular or respiratory conditions. Exposure to cold air causes a
      rise in blood pressure and haemoconcentration which lead to increased tendency to
      vascular thromboses. In hot weather, haemoconcentration due to sweating and
      perspiration increases blood viscosity and the risk of thrombosis. Both cold and
      heat are significant public health hazards which should be taken into account in
      health care and education of health professionals.

PMID- 16440609
TI  - The potential impact of climate change on infectious diseases of Arctic fauna.
AB  - Climate change is already affecting Arctic species including infectious disease
      agents and greater changes are expected. Some infectious diseases are already
      increasing but future changes are difficult to predict because of the complexity
      of host-agent-environment relationships. However mechanisms related to climate
      change that will influence disease patterns are understood. Warmer temperatures
      will benefit free living bacteria and parasites whose survival and development is
      limited by temperature. Warmer temperatures could promote survivability, shorter
      development rates and transmission. Insects such as mosquitoes and ticks that
      transmit disease agents may also benefit from climate change as well as the
      diseases they spread. Climate change will have significant impacts on
      biodiversity. Disease agents of species that benefit from warming will likely
      become more prevalent. Host species stressed by changing environmental conditions
      may be more vulnerable to disease agents. Warming could lead to increased
      agriculture and other economic opportunities in the Arctic bringing people,
      domestic food animals, pets and invasive species and their disease agents into
      Northern regions. Climate warming may also favor the release of persistent
      environmental pollutants some of which can affect the immune system and may favor
      increased rates of some diseases.

PMID- 16440610
TI  - Potential impacts of climate change on infectious diseases in the Arctic.
AB  - Climate change could cause changes in the incidence of infectious diseases in
      Arctic regions. Higher ambient temperatures in the Arctic may result in an
      increase in some temperature sensitive foodborne diseases such as
      gastroenteritis, paralytic shellfish poisoning and botulism. An increase in mean
      temperature may also influence the incidence of infectious diseases of animals
      that are spread to humans (zoonoses) by changing the population and range of
      animal hosts and insect vectors. An increase in flooding events may result in
      outbreaks of waterborne infection, such as Giardia lamblia or Cryptospordium
      parvum. A change in rodent and fox populations may result in an increase in
      rabies or echinococcosis. Temperature and humidity influence the distribution and
      density of many arthropod vectors which in turn may influence the incidence and
      northern range of vectorborne diseases such as West Nile virus. Recommendations
      include: the strenghtening of public health systems, disease surveillance
      coordinated with climate monitoring, and research into the detection, prevention,
      control and treatment of temperature-sensitive infectious diseases.

PMID- 16440611
TI  - Climate change and human health: infrastructure impacts to small remote
      communities in the north.
AB  - In northern regions, climate change can include changes in precipitation
      magnitude and frequency, reductions in sea ice extent and thickness, and climate
      warming and cooling. These changes can increase the frequency and severity of
      storms, flooding, or erosion; other changes may include drought or degradation of
      permafrost. Climate change can result in damage to sanitation infrastructure
      resulting in the spread of disease or threatening a community's ability to
      maintain its economy, geographic location and cultural tradition, leading to
      mental stress. Through monitoring of some basic indicators communities can begin
      to develop a response to climate change. With this information, planners,
      engineers, health care professionals and governments can begin to develop
      approaches to address the challenges related to climate change.

PMID- 16440612
TI  - The potential impact of climate on human exposure to contaminants in the Arctic.
AB  - Many northern indigenous populations are exposed to elevated concentrations of
      contaminants through traditional food and many of these contaminants come from
      regions exterior to the Arctic. Global contaminant pathways include the
      atmosphere, ocean currents, and river outflow, all of which are affected by
      climate. In addition to these pathways, precipitation, animal availability, UV
      radiation, cryosphere degradation and human industrial activities in the North
      are also affected by climate change. The processes governing contaminant
      behaviour in both the physical and biological environment are complex and
      therefore, in order to understand how climate change will affect the exposure of
      northern people to contaminants, we must have a better understanding of the
      processes that influence how contaminants behave in the Arctic environment.
      Furthermore, to predict changes in contaminant levels, we need to first have a
      good understanding of current contaminant levels in the Arctic environment, biota
      and human populations. For this reason, it is critical that both spatial and
      temporal trends in contaminant levels are monitored in the environment, biota and
      human populations from all the Arctic regions.

PMID- 16440613
TI  - Arctic stratospheric ozone depletion and increased UVB radiation: potential
      impacts to human health.
AB  - Contrary to popular belief, stratospheric ozone depletion, and the resultant
      increase in solar UV-B (280-320 nm), are unlikely to fully recover soon.
      Notwithstanding the success of the Montreal Protocol in reducing the amount of
      ozone destroying chemicals into the stratosphere, the life-times of these
      compounds are such that even with full compliance with the Protocol by all
      countries, it will be decades before stratospheric ozone could return to pre-1980
      levels. This raises the question, therefore, of what will happen to biological
      processes essential to the maintenance of life on earth which are sensitive to
      damage by increased UV-B radiation, particularly those involved with human
      health? The polar regions, because of the vagaries of climate and weather, are
      the bellwether for stratospheric ozone depletion and will, therefore, be the
      first to experience impacts due to increases in solar UV-B radiation. The impacts
      of these are incompletely understood and cannot be predicted with certainty.
      While some UV-B impacts on human health are recognized, much is unknown, unclear
      and uncertain. Thus, this paper attempts, as a first approximation, to point out
      potential impacts to the health and welfare of human inhabitants of the Arctic
      due to increased solar UV-B radiation associated with stratospheric ozone
      depletion. As will be seen, much more data is critically needed before adequate
      risk assessment can occur.

PMID- 16440614
TI  - Environmental variables and the risk of disease.
AB  - OBJECTIVES: To study the relation between the risk of acute myocardial
      infarctions (AMI) and meteorological variables and the geomagnetic field, and to
      make a literature survey of the relation between environmental variables and the
      occurrence of disease. STUDY DESIGN: Register study and literature search.
      METHODS: Register data on AMI were analysed together with data on temperature,
      relative humidity, barometric pressure, the Arctic Oscillation, the earth's
      magnetic field, and changes in these variables. A PubMed search for studies on
      environmental variables and the occurrence of other diseases was done. RESULTS:
      There was no correlation between "static" weather variables and the number of
      AMIs. A temperature rise of one degree C was associated with an increase in the
      number of non-fatal AMIs by 1.5%. There was a strong correlation between the AO
      and the number of AMIs--a one unit increase in AO caused an increase in the
      number of surviving AMIs by 3.4%, fatal AMIs by 5.1% and the number of sudden
      cardiac deaths by 8.3%. There was no association between the geomagnetic field
      and the number of AMIs. The literature study revealed that several other disease
      states were related to extremes of or changes in weather situations. CONCLUSIONS:
      A change in weather, rather than weather extremes, was associated with an
      increase in the number of AMIs. The environment surrounding us is capable of
      causing both disease and symptoms. The triggering mechanisms are not known,
      though.

PMID- 16440615
TI  - [Those who cannot remember the past are condemned to repeat it].
AB  - To the casual observer, the history of medicine seems one of continuous progress.
      In reality, for every therapeutic accomplishment that has withstood the test of
      time there have been several ineffective or even harmful treatments that are now
      forgotten; yet they were based on theories regarded as plausible at the time.
      Examples abound, also in the archives of the Dutch Journal of Medicine:
      treatments for poliomyelitis and sciatica provide striking illustrations. Even in
      the current era of controlled trials and meta-analyses, physicians need to be
      reminded that a logical theory in itself does not justify treatment decisions
      unless it is supported by experimental evidence. The essential difference between
      mainstream medicine and complementary medicine is not the plausibility of the
      underlying theories but the rigour in testing hypotheses. On the other hand, many
      decisions in medicine must be made without sufficient evidence. Logic is
      indispensable but should be part of an empirical cycle in which new thoughts lead
      to new experiments and vice versa.

PMID- 16440616
TI  - [Cyclic vomiting in children].
AB  - Two girls aged 13 and 10 suffered from recurrent episodes of severe vomiting.
      After excluding underlying pathological conditions the diagnosis of cyclic
      vomiting syndrome was made. They were treated by intravenous fluid suppletion and
      drugs such as propranolol, pizotiphene, diclophenac, granisetron, lorazepam and
      pantoprazole. Eventually they recovered. Cyclic-vomiting syndrome is probably a
      common but often not recognised syndrome. It should be considered in all children
      with multiple episodes of vomiting. It is characterized by the sudden occurrence
      and spontaneous disappearance of symptoms followed by a completely symptom-free
      interval. The incidence has been estimated to be as high as 2% in some
      populations of school children. The syndrome is often not diagnosed if the
      episodes are mild and diagnosed late if the symptoms are severe. To avoid too
      many investigations the suggested diagnostic protocol can be followed.
      Prophylactic therapy with anti-migraine medication should be attempted, notably
      with propranolol, early in the course of the disease.

PMID- 16440617
TI  - [The great important of tumor-free margins in the breast-saving procedure].
AB  - There is increasing evidence that local recurrence after breast-conserving
      surgery may lead to an increase in distant metastases and disease-specific
      mortality. The most important factor responsible for recurrence is the margin
      status after excision. The treatment of patients with breast cancer should be
      decided upon by a multidisciplinary treatment group so that the candidates for a
      breast-conserving procedure can be adequately selected with emphasis on achieving
      maximum local control.

PMID- 16440618
TI  - [Treatment of servere ulcerative colitis].
AB  - 10-15% of patients with ulcerative colitis experience a severe episode of colonic
      inflammation that does not respond to mesalazine and oral corticosteroids. These
      patients require hospitalisation and treatment with intravenous corticosteroids.
      However, 25% of these patients do not respond to treatment. In these cases,
      intravenous cyclosporin is effective. Infliximab, an antibody against tumour
      necrosis factor alpha, is also beneficial. With these new treatment options, the
      colectomy rate in the acute phase has declined to about 35%. Other new therapies
      are under investigation in phase 2 and 3 trials. Surgery remains an important
      treatment option. Patients, gastroenterologists and surgeons should be involved
      in the clinical decision-making process.

PMID- 16440619
TI  - [The practice guideline 'Diagnosis and treatment of familial
      hypercholesterolaemia' of the Dutch Health Care Insurance Board].
AB  - Until 2010, the Dutch ministry of Health, Welfare and Sport will fund a
      nationwide project to identify the approximately 40,000 patients with familial
      hypercholesterolaemia (FH) in the Netherlands. The Health Care Insurance Board
      will coordinate the project and safeguard its quality, while the 'Stichting
      Opsporing Erfelijke Hypercholesterolemie' [Foundation for the Detection of
      Hereditary Hypercholesterolaemia], with its national network of genetic
      fieldworkers, will search systematically within families with assessed FH
      mutations. The referral of the first suspected case of FH in a family for DNA
      diagnosis remains a task for GPs, internists and other clinical professionals;
      these will also be expected to take the responsibility for treatment. The list of
      diagnostic criteria of the 'Dutch Lipid Clinic Network' has recently been
      validated and is recommended as a decision-tool for initiating DNA diagnosis.
      After confirmation of the DNA diagnosis, the plasma level of LDL-cholesterol
      remains the main criterion for pharmacotherapy; treatment with
      hypocholesterolaemic agents is recommended at levels above 2.5 mmol/l.

PMID- 16440620
TI  - [The guideline 'Psychiatric evaluation in adults'].
AB  - Psychiatric evaluation is defined as a systematic evaluation of the causes, the
      symptoms, the course and the consequences of a psychiatric disorder in order to
      formulate a diagnosis and a treatment plan, and to answer any questions the
      patient or referring specialist may have. The main components of a comprehensive
      psychiatric evaluation are the patient interview and observations of the
      patient's behaviour. The comprehensiveness of the psychiatric evaluation is
      affected by contextual, patient-related and situational factors. In the
      psychiatric diagnosis a distinction is made between the diagnostic classification
      (according to the DSM-IV-classification) and a structural diagnosis. The sequence
      ofthe elements ofthe psychiatric evaluation is based on medical tradition. In the
      mental-status examination all objective and subjective psychiatric symptoms are
      systematically reviewed. The grouping of the symptoms is based upon the classical
      division of mental functions into cognitive, affective and conative functions.

PMID- 16440621
TI  - [Diagnostic image (256). A boy with bilateral cervical lymphadenopathy].
AB  - A teenage boy was seen with a swollen neck due to tuberculous cervical
      lymphadenitis.

PMID- 16440622
TI  - [The long-term prognosis of locally recurrent breast cancer after breast
      conserving treatment].
AB  - OBJECTIVE: To study the long-term prognosis of patients with locally recurrent
      breast cancer following breast-conserving treatment. DESIGN: Descriptive. METHOD:
      Data were collected on 266 patients in 11 Dutch centres; in these patients, an
      isolated local recurrence of an infiltrating mammary carcinoma for which they had
      received breast-conserving treatment was diagnosed before January 1st, 1994. The
      median age was 45 years (range 16-81) at the time of treatment of the primary
      tumour and 49 years (range 17-82) at the time of diagnosis of the local
      recurrence. The patients were followed through December 2002. The median follow
      up after local recurrence of those patients who were still alive was 11.2 years.
      RESULTS: Of the 226 patients with an infiltrating local recurrence, 148 (65%) had
      died and 145 (64%) had developed distant metastases. Of the metastases, 61%
      appeared within 2.5 years and 87% within 5 years after treatment of the local
      recurrence. 10 years after treatment of the local recurrence, the overall
      survival rate was 39% (95% CI: 32-46) and the distant metastasis-free survival
      rate was 36% (95% CI: 29-42). The prognosis of patients with a local recurrence
      occurring at a different site in the breast was the same as that of patients with
      a local recurrence < or = 1 cm in diameter occurring at or near the original
      tumour site. Both of these groups had a better prognosis than patients with a
      recurrence larger than 1 cm at the site of the original tumour or patients with a
      diffuse recurrence. CONCLUSION: Almost two-thirds of the patients with an
      invasive local recurrence following breast-conserving surgery for invasive breast
      cancer developed distant metastases. Both the exact location in the breast and
      the size of the local recurrence appeared to be predictors of the risk of
      subsequent metastatic disease.

PMID- 16440623
TI  - [Intermittent vomiting in a patient with superior mesenteric artery syndrome].
AB  - A 51-year-old woman presented with nausea, vomiting and weight loss. The
      diagnosis of superior mesenteric artery syndrome was established by CT and upper
      gastrointestinal contrast radiography. This revealed a characteristic dilatation
      of the first and second parts of the duodenum and an abrupt cutoff in the third
      part due to vascular compression. The obstruction disappeared when the patient
      was placed in the left lateral recumbent position. The thin habitus of this
      patient probably played an important role in the development of the syndrome. She
      was given dietary and positioning advice and within 4 months relief of symptoms
      was accompanied by a weight gain of 4 kg.

PMID- 16440624
TI  - [Historical health posters as expressions of public health dilemmas].
AB  - Historical health posters as expressions of public health dilemmas. The
      University of Amsterdam's historical collection of health and safety posters
      (1914-1960) from various countries deals primarily with workplace safety,
      infectious diseases and the early detection of cancer. Distinct underlying socio
      medical dilemmas emerge in four areas: the industrial-political issues behind
      promoting responsible behaviour in the workplace; class issues in public
      tuberculosis education; public morality in anti-venereal propaganda, and dealing
      with fear and hope in the management of cancer. The main goal of the historical
      posters was to establish a general awareness of both health and individual
      responsibility. Yet this collection illustrates how socio-medical, political and
      cultural contextual factors strongly influenced the message and style of the
      posters.

PMID- 16440626
TI  - [Breech presentation: infant versus mother].

PMID- 16440627
TI  - [Pneumocystis pneumonia during infliximab treatment for active Crohn's colitis].

PMID- 16440628
TI  - [Prostate carcinoma: requests from the urologist for the pathologist].

PMID- 16440629
TI  - Gleason grading of prostate cancer. Contemporary approach.

PMID- 16440630
TI  - [Prostatic cancer: molecular bases].

PMID- 16440631
TI  - [Neoplastic pathology of the prostate: perspectives].

PMID- 16440632
TI  - [Studies of molecular morphology with immunohistochemistry in breast ductal
      proliferations].

PMID- 16440633
TI  - [Neoplastic pathology of the breast: perspectives].

PMID- 16440635
TI  - [Lung cancer: molecular bases].

PMID- 16440634
TI  - [Problematic aspects and controversies in pleuro-pulmonary histopathologic
      diagnosis].

PMID- 16440636
TI  - Pleura: basi molecolari. Pleura: molecular bases.

PMID- 16440637
TI  - [Targeted therapy in non-small cell lung tumors: recent findings and future
      perspectives].

PMID- 16440638
TI  - [Inflammatory and metaplasia lesions in the esophagogastric junction].

PMID- 16440639
TI  - [Transforming agents and molecular bases of carcinogenesis].

PMID- 16440640
TI  - Accumulation of genetic changes during the development and progression of bladder
      cancer.

PMID- 16440641
TI  - [Morphogenetic and molecular events in the early stages of colorectal
      carcinogenesis].

PMID- 16440643
TI  - [Prognostic/predictive role of epidermal growth factor receptor (EGFR) in
      colorectal carcinoma].

PMID- 16440645
TI  - [Diagnostic and prognostic markers in renal tumors].

PMID- 16440646
TI  - [Stem cells: overview].

PMID- 16440648
TI  - [Bone stem cells].

PMID- 16440647
TI  - Investigation on possible cell sources to be utilized for cardiac cell therapy.

PMID- 16440649
TI  - [Tissue microarrays].

PMID- 16440650
TI  - DNA mitocondriale e CGH array in patologia mammaria.

PMID- 16440651
TI  - [Proteomics analysis of solid tumors].

PMID- 16440652
TI  - Tecniche "high throughput" in patologia umana. Biostatistica. "High throughput"
      technique in human pathology. Biostatistics.

PMID- 16440653
TI  - [Human tissue banks: objectives and regulatory aspects in Italy and Europe].

PMID- 16440654
TI  - [Frozen tissue bank. Presuppositions, operative level and organization
      structure].

PMID- 16440655
TI  - [Frozen tissue bank: experience of the Tumor National Institute of Milan].

PMID- 16440656
TI  - [Autopsy control: norms and recommendations].

PMID- 16440657
TI  - [The pathologist and transplant safety: the histologic control].

PMID- 16440658
TI  - [The cyto-histologic comparison].

PMID- 16440659
TI  - [Progression marker in gynecologic (cervical) cytology].

PMID- 16440660
TI  - [Progression markers in gynecologic (endometrial) cytology].

PMID- 16440661
TI  - [FISH and thin layer in urinary cytology].

PMID- 16440662
TI  - [Contribution of immunocytochemistry in cytology].

PMID- 16440663
TI  - [Immunohistochemistry in thyroid needle aspiration samples].

PMID- 16440664
TI  - [Nucleic acids: extraction of archival material].

PMID- 16440665
TI  - [PCR: potential and problems].

PMID- 16440666
TI  - [Alterations of gene methylation].

PMID- 16440667
TI  - [Methods for the study of mutations].

PMID- 16440669
TI  - [Role of the FISH and CISH techniques in the analysis of HER2].

PMID- 16440670
TI  - [Assessment of a new test for the study of messenger RNA in the diagnosis of
      Papilloma virus].

PMID- 16440671
TI  - [Spectrum of neuroendocrine tumors in non-endocrine organs].

PMID- 16440672
TI  - Investigation of alcohol use disorders in a group of driving-while-intoxicated
      offenders.
AB  - This preliminary study was carried out to investigate alcohol use disorders and
      personality profiles in a group of driving-while-intoxicated offenders. Thirty
      nine volunteer offenders were assessed by CAGE, while 21 of them were assessed by
      SCID-I Alcohol and Drug Use Disorders module and 14 drivers completed MMPI test.
      According to CAGE scores, 11 was found to have an indication of alcohol problem
      and 7 had clinically significant alcohol use disorder. Within 21 drivers, 4 had a
      DSM-IV diagnosis of alcohol abuse. Independent of their diagnosis, MMPI profiles
      revealed the psychopathic personality characteristics which might explain
      drinking while driving as a risky behaviour in this group. These results suggest
      that, besides legal applications, referring offenders to associated centers, in
      order to be evaluated and informed about alcohol use disorders, would be an
      important step in the prevention of recurrent alcohol impaired driving as well as
      alcohol related incidents.

PMID- 16440674
TI  - [Interrelationship among factors associated with drinking behaviors in dental
      students].
AB  - We analyzed the Kurihama Alcoholism Screening Test (KAST), the Adolescent Alcohol
      Involvement Scale (AAIS), the Fagerstroem Tolerance Questionnaire (FTQ), the
      Tokyo University ALDH2-Phenotype Screening Test (TAST), results of ethanol patch
      tests, the presence or absence of a smoking habit, and gender by "Hayashi's
      quantification theory, type II" in 415 senior students (232 males and 183
      females) of a dental college between 2000 and 2003, and evaluated their
      relationships. When drinking education is given to dental students, both the
      prevention of acute alcohol intoxication by chugging and the prevention of
      alcohol dependence in students with drinking behavior suggesting this tendency
      are necessary. For acute alcohol intoxication, attention can be aroused in
      students with positive ethanol patch tests. However, there is no definite
      instruction method for the prevention of alcohol dependence. Therefore, we
      analyzed the relationships among drinking, smoking, and constitution based on
      data obtained during the 4 years when the above 3 types of surveys were
      performed. Plotting of the results of analysis showed that the students can be
      classified by the ethanol patch test and TAST into those with "alcohol-sensitive"
      constitution and those with "alcohol-tolerant" constitution. Most problem
      drinkers were "alcohol-tolerant". KAST showed plotting along the constitution
      axis from "normal drinking group" to "problem drinking borderline group" but a
      change in the angle to an L shape at the transfer point from "problem drinking
      borderline group" to "problem drinking group", showing more serious states along
      the smoking axis. These results suggest that drinking behavior is first regulated
      by alcohol- sensitive or alcohol-tolerate constitution, and alcohol-tolerate
      students with a smoking habit have alcohol dependence tendency, and tend to show
      serious problem drinking. Improvement in the drinking habit is necessary in
      alcohol-tolerate students with a smoking habit so that they will not develop
      alcohol dependence.

PMID- 16440673
TI  - [Comparative studies on patient's and family's basic attributes, psychosocial
      states and treatment prognoses at three medical institutions for treatment of
      alcoholism].
AB  - A research by questionnaire was conducted at three medical institutions, on basic
      attributes and psychosocial states of alcoholics' as first time inpatient and
      respective families. After a year of research, additional study was conducted in
      regard of abstinence, treatment continuation as outpatient, participation in self
      help groups, and family's participation in family groups. Outcomes of researches'
      statistical analyses showed significant differences concerning medical
      institutions and basic attributes for the items: treatment histories of
      alcoholism, treatment or inpatient in other medical departments and alcoholic's
      family history,; but these differences were considered to be associated with
      varied courses of referrals. In relation to medical institutions with patients
      and family's psychosocial states, there were no significant differences on the
      outcomes of five scales. As for the correlation between medical institutions with
      a year's prognoses there were no significant differences concerning abstinence
      and treatment continuation as outpatient. In case of participation in self-help
      groups and family groups, the prognoses showed significant differences but these
      differences were considered to be related to varied treatments and different
      helping ways of medical institutions and varied conditions of local communities
      for mentioned helps.

PMID- 16440675
TI  - [Factors promoting Japanese adolescent problem drinking in a cohort study over 5
      years].
AB  - This report outlines factors promoting adolescent problem drinking at 5 years
      after the start of a cohort study. We started the first longitudinal cohort study
      on Japanese adolescent alcohol use and misuse in 1997. The purpose of the cohort
      study was to show factors that promote adolescent drinking and whether adolescent
      problem drinking will develop into the early alcohol dependence syndrome. Eight
      hundred and two subjects whose mean age was 13.5 years old were recruited from
      four junior high schools in Kanagawa prefecture. The survey was conducted
      annually by mail using self-reported questionnaires concerning adolescent
      drinking and alcohol-related problems. In the 2002 survey at 5 years after the
      starting point, the respondents numbered 557 with a mean age of 18.8 year old,
      and the follow-up rate was 70%. In the 2002 survey, 17.5% of the subjects were
      found to be problem drinkers from the scores of the core-AUDIT. We divided the
      subjects into three groups according to the scores of the core- AUDIT: problem
      drinkers, drinkers and abstainers. The three groups were compared concerning
      family relationships, first drinking age and drinking status of parents with the
      responses of the 1997 survey. In the comparison of the three groups, many factors
      were significantly different, and a logistic regression analysis was performed on
      these factors to determine drink promoting factors. Three factors were
      determined: having drinking experiences at 13.5 years old at the start of the
      survey, not refusing friends' temptations to drink and less communication with
      their parents. The results were very important because these three factors were
      described by many authors as adolescent drinking promoting factors.

PMID- 16440676
TI  - [Regional cerebral blood flow and WAIS-R in alcohol drinkers].

PMID- 16440677
TI  - [Assessment of surgery for stage IV non-small cell lung cancer].
AB  - We assessed the survival of surgery for stage IV non-small cell lung cancer.
      Forty-two patients were operated on lung cancer for stage IV from 1986 to 2005.
      Overall median survival time (MST) was 12.3 months and 5-year survival rate was
      9.8%. There was significant difference in survival between pulmonary metastasis
      (pm2) and other sites metastasis (p<0.05). In pm2 patients there was significant
      difference between ipsilateral metastasis and contralateral metastasis (MST 21.9
      months, 2-year survival rate 48.6%, 5-year survival rate 21.6% and MST 12.3
      months, 2-year survival rate 0%) [p<0.05], and between complete resection and
      incomplete resection (MST 36 months, 2-year survival rate 64.8%, 5-year survival
      rate 28.8% and MST 12.3 months, 2-year survival rate 0%) [p<0.01]. In patients
      with brain metastasis, surgery of brain metastasis was better prognosis than
      radiation therapy (MST 12.5 months, 3-year survival rate 33.3% and MST 8.3
      months, 2-year survival rate 0%) [NS].

PMID- 16440678
TI  - [Analysis of surgical treatment of primary lung cancer having M1 diseases].
AB  - The presence of distant metastasis is thought as systemic dissemination of
      disease. Patients with lung cancer in this category are not usually considered
      candidates for surgical resection of the primary and metastatic sites. The
      purpose of this study is to determine long-term survival and identify potential
      prognostic factors for surgical treatment to primary non-small cell lung cancer
      with distant metastasis. We conducted a retrospective analysis of the surgical
      outcome of 24 patients who were classified as having M1 disease. The 5-year
      survival rate was 34.6% in our facility. Among the 12 patients had N2 disease and
      a poor prognosis. Long-term survival can be achieved if the metastatic site is
      lung and there is no lymph node involvement, although differentiation of
      pulmonary metastasis and multiple primary lung cancer is commonly difficult.

PMID- 16440679
TI  - [Surgical indication for non-small cell lung cancer with synchronous distant
      metastases].
AB  - From 1989 to 2004, 20 patients with synchronous distant metastases
      [intrapulmonary metastases (n=10) and extrapulmonary metastases (n=10)] underwent
      surgery for primary lesion of non-small cell lung cancer (NSCLC). Complete
      resection of the primary tumor and metastases was achieved in 5 patients. Overall
      1- and 2-year survival rates were 48 and 11%, respectively, and mean survival was
      21 months. The corresponding figures for patients with pulmonary metastasis to
      another lobe were 78, 23%, and 35 months, and those for patients with distant
      metastasis to a site other than another pulmonary lobe were 20, 0%, and 7 months.
      Two patients with pulmonary metastasis survived more than 5 years. With pulmonary
      metastasis to another lobe prognosis was better than that with distant metastasis
      to another site. Survival was not affected by histology or N factor. Complete
      resection tended to be a factor contributing to a better clinical outcome. This
      study suggests that surgery for NSCLC with synchronous distant metastasis should
      be indicated only for patients who could be expected to undergo complete excision
      of both the primary and metastasis lesion, as a clinical study under informed
      consent.

PMID- 16440680
TI  - [Survival after surgical resection for stage IV non-small cell lung cancer].
AB  - We analyzed 20 patients with stage IV non-small cell lung cancer operated from
      1988 to 2003. Fourteen out of 20 were cases with pulmonary metastasis (pm2). The
      prognosis of patients with pm2 was better than that of those with distant organ
      metastasis. In pm2 patients, the survival rate of cases without lymph node
      metastases was higher than those with lymph node metastases. It is suggested that
      in cases of pm2 without lymph node metastases, surgical operation is possibly
      effective treatment of choice.

PMID- 16440681
TI  - [Prognosis of patients after resection for lung cancer with intrapulmonary
      metastasis in different lobes].
AB  - BACKGROUND: The prognosis of lung cancer patients with intrapulmonary metastasis
      in different lobes (pm2) is poor. However, some patients achieve long-term
      survival. We retrospectively investigated the prognosis of resected primary lung
      cancer patients with pm2. METHOD: Among 845 patients with primary lung cancer who
      underwent complete resection from 1984 to 2003, 14 cases that had lung cancer
      with pm2 were evaluated about prognostic factors. RESULTS: The overall 5-year
      survival rate was 9.5%. The analysis of survival curve based on
      clinicopathological factors (surgical procedure, histology, tumor size, lymph
      nodal metastasis, pleural invasion, pleural dissemination and number of pm2)
      revealed that bronchioloalveolar carcinoma (BAC), the absence of pleural invasion
      and the absence of pleural dissemination are better prognostic factors.
      CONCLUSION: Lung cancer patients with pm2 whose lesions show BAC histology, the
      absence of pleural invasion or pleural dissemination may achieve long-term
      survival and could be candidates for surgical treatment.

PMID- 16440682
TI  - [Surgical approach for lung cancer with multiple pulmonary nodules].
AB  - A computed tomography (CT) and high-resolution CT (HRCT) have provided us an
      increasing opportunity to find multiple small pulmonary nodules, which sometimes
      appear ground glass opacity (GGO). Recently, fluorodeoxyglucose-positron emission
      tomography (FDG-PET) had a great contribution to our assessment for these small
      pulmonary nodules. However, since it is yet difficult to establish a diagnosis
      for these nodules during preoperative workup, a surgical lung biopsy is often
      required for an accurate diagnosis. We have experienced 9 patients who had
      undergone lung resection for primary lung cancer accompanied by multiple
      pulmonary lesions. Since the multiple lesions were consisted of malignant and
      benign lesions, it is still uncertain whether excessive lung resection should be
      performed in such patients. In this brief article, we summarized the
      characteristics of the pulmonary lesions in those patients and discussed
      difficulty of preoperative diagnosis, viability of pulmonary resection and
      problems underlining a surgical treatment.

PMID- 16440683
TI  - [Surgical treatment for stage IV lung cancer].
AB  - OBJECTIVE: To find out the optimal surgical indication in stage IV lung cancer
      patients, we evaluated them retrospectively. METHODS & RESULTS: From 1975 to
      2005, 62 patients without multiple metastases were operated at our hospital. The
      most common histological type was adenocarcinoma (67.7%). The metastatic lesions
      were lung (33.9%), brain (24.2%), liver, bone, adrenal gland and so on. The
      overall survival rate of stage IV lung cancer was 10.4% at 5-year. Five-year
      survival for patients with lung or brain metastasis who had no lymph node
      metastasis were significantly more superior than those with lymph node metastasis
      (p=0.0389, 0.0021). Four of 62 patients had 5-year survival. Two were lung and
      the others were brain and adrenal gland metastasis without lymph node metastasis.
      CONCLUSION: Stage IV lung cancer with lung or brain or adrenal gland metastasis
      without lymph node metastasis should be resected.

PMID- 16440684
TI  - [Surgical treatment for primary non-small cell lung cancer with synchronous brain
      metastases].
AB  - The brain is one of the most common sites of metastasis from lung cancer. The
      strategies of treatment for non-small cell lung cancer patient with synchronous
      brain metastases (stage IV) is controversial. We evaluate retrospectively the
      effectiveness of surgical treatment for these patients. Forty patients were
      divided into 3 groups on the basis of surgical treatment, group A of patients
      received both lung and brain resection, group B of patients received lung
      resection plus gamma knife therapy, group C of patients received brain resection.
      Median survival from the date of diagnosis of brain metastasis was as follows:
      group A 331 days, group B 151 days and group C 92 days. Univariate analysis
      revealed that adenocarcinoma histology and serum LDH significantly affected
      survival. Multivariate analysis found that only adeocarcinoma histology also
      affected the survival. It is concluded that surgical treatment may acceptable in
      selected group of non-small cell lung cancer patients with synchronous brain
      metastases.

PMID- 16440685
TI  - [Surgical treatment for adrenal metastasis from lung cancer].
AB  - Several long-term survivors after surgical resection for a solitary adrenal
      metastasis from non-small cell lung cancer (NSCLC) have been reported in case
      reports and case series with a small number of patients. We have experienced 6
      cases of patients who had adrenalectomy (ADR) for a metastasis from NSCLC. The
      median survival time (MST) after ADR was 24 months, and there was only 1 case of
      3-year survivor. To elucidate the surgical indication and the prognostic factors
      of patients with a solitary adrenal metastasis from NSCLC, we analyzed 104
      patients including our 6 patients who had ADR for a metastasis from NSCLC. The
      MST after ADR and 5-year survival were 24 months and 31%, respectively.
      Univariate and multivariate analysis demonstrated that lymph node metastasis at
      the surgery for primary lung cancer was the only significant and independent
      predictor of poor survival in patients after ADR. The results suggest that
      aggressive surgical treatment of a solitary adrenal metastasis from NSCLC may be
      effective when a patient have N0 disease.

PMID- 16440686
TI  - [Review of the surgical treatment in superior sulcus tumor].
AB  - The rarity of the superior sulcus tumor has led to varying treatment techniques.
      Generally, radiation therapy followed by surgery has been used. En bloc resection
      combined with lobectomy and nodal dissection remains standard therapy. The unique
      location of this tumor, surgical approach thought to be important. Involvement of
      the anterior areas such as subclavian vessels can be resected by anterior
      transcervical approach, and vertebral body or brachial plexus through the classic
      Shaw Paulson approach. Preoperative computed tomography (CT) or magnetic
      resonance imaging (MRI) is beneficial to the evaluation of the vessels, nerves,
      and surgical planning. Recent studies showed that induction concurrent
      chemoradiation therapy improved the resectability and curability. This article
      reviews the treatment of superior sulcus tumor.

PMID- 16440687
TI  - [Valve-in-valve replacement of primary tissue valve failure of bovine pericardial
      valve minor].
AB  - A 73-year-old woman who underwent mitral valve replacement with a 31 mm
      Carpentier Edwards Pericardial Xenograft 19 years ago. She revealed sudden onset
      of a grade IV/VI a seagull like diastolic murmur at the apex, and severe
      hematuria. Echocardiography demonstrated severe mitral regurgitation. These
      findings were consistent with acute primary tissue valve failure. Therefore we
      performed emergency reoperation. At operation, valve leaflet was torn at the
      commissural stitch, and bioprosthesis strut was buried in the left posterior
      ventricular wall. The mitral prosthetic valve replaced with a 25 mm CarboMedics
      OptiForm using a technique of valve-in-valve replacement. This procedure would be
      one option for replacement of bioprosthetic mitral valve.

PMID- 16440688
TI  - [Infectious endocarditis complicated with preoperative cerebral infarction and
      rupture of infectious intracranial aneurysm].
AB  - A surgically treated case of infectious endocarditis (IE) complicated with
      preoperative cerebral infarction and rupture of mycotic intracranial aneurysm was
      reported. A 66-year-old male was admitted with the diagnosis of active IE due to
      Streptococcus sanguis, complicated with cerebral infarction 17 days previously.
      Preoperative echocardiography showed mobile vegetations both on the aortic and
      the mitral leaflet, sizes of which were 12.6 and 25 mm. The magnetic resonance
      imaging (MRI) demonstrated a subarachnoid homorrhage due to the rupture of an
      intracranial aneurysm, and was treated surgically. The bacteriological study of
      the resected aneurysm showed Streptococcus sanguis. Eleven days after the
      operation, both the aortic and the mitral valve replacement were performed. There
      were mobile vegetations on the aortic and the mitral leaflet. There were no new
      neurological findings after operation. The duration between the cranial surgery
      and the cardiac surgery was thought to be important to prevent the new
      neurological complication.

PMID- 16440690
TI  - [Right spontaneous pneumothorax which accompanied absence of right pulmonary
      artery].
AB  - A case had a checkup for dyspnea with a man of 70-year-old, and it was diagnosed
      as the recurrent right spontaneous pneumothorax. Bulla was found in the right
      lung with a chest computed tomography (CT), and absence of right pulmonary artery
      was suspected. Absence of right pulmonary artery was diagnosed by pulmonary
      arteriography. Re-examination of the patient's chest X-ray from the previous 11
      years revealed a chronological decrease of right lung volume and an increase of
      the cardiothoracic ratio. We performed right bullectomy by thoracoscopic
      assistance. The postoperative course was uneventful.

PMID- 16440689
TI  - [Effects of intra-coronary and intra-graft administration of nicorandil for
      coronary spasm after coronary artery bypass grafting].
AB  - Coronary artery spasm after coronary artery bypass grafting (CABG) is relatively
      rare, but when it occurs, it is fatal. In cases of circulatory collapse just
      after surgery, coronary spasm should be suspected, and immediate diagnosis by
      coronary angiography is necessary. We conducted a study to assess the clinical
      characteristics of coronary spasm after CABG and the usefulness of intra-coronary
      and intra-graft administration of nicorandil. Study subjects were 7 patients (6
      men and 1 woman, mean age 60.4 years) in whom coronary spasm after CABG was
      diagnosed angiographically from January 1992 to December 2003. Off-pump CABG
      (OPCAB) had been performed in 2 patients. Despite continuous administration of
      nitroglycerin and diltiazem hydrochloride during surgery, sudden circulatory
      collapse occurred during surgery or within 24 hours after CABG in all 7 patients.
      All required mechanical circulatory support, and emergency coronary angiography
      revealed severe graft and native coronary spasms. Intracoronary and/or intra
      graft administration of diltiazem hydrochloride or nitroglycerin was not very
      effective, however, administration of nicorandil was effective for
      vasodilatation. One patient suffered brain damage and died, but the other 6
      patients recovered and were discharged without complication. In conclusion, intra
      coronary and/or intra-graft administration of nicorandil appears to be useful for
      the treatment of coronary spasm after CABG.

PMID- 16440691
TI  - [Coronary artery bypass grafting in a patient with right aortic arch; report of a
      case].
AB  - A 60-year-old man was admitted to another hospital because of chest oppression on
      effort. Chest X-ray showed radiographic evidence of a right aortic arch and
      double vessel coronary artery disease with 50% stenosis in the left main trunk
      was diagnosed by coronary angiography. He was transferred to our institute for
      surgical treatment of angina pectoris. Preoperatively, multi-detector row
      computed tomography (CT) was performed and it revealed a right aortic arch and an
      aberrant left subclavian artery with narrow left internal thoracic artery. A
      right internal thoracic artery was well demonstrated. Therefore, conventional
      coronary artery bypass grafting using a right internal thoracic artery and a
      saphenous vein graft was performed and his postoperative course was uneventful.

PMID- 16440692
TI  - [Future direction of endovascular neurosurgery].

PMID- 16440693
TI  - [Transcranial approach to orbital tumor].

PMID- 16440694
TI  - [Mask anesthesia for cerebral angiography in childhood moyamoya disease].
AB  - Cerebral angiography is performed for diagnosis and management of moyamoya
      disease and in childhood moyamoya disease is usually carried out under general
      anesthesia after tracheal intubation. Mechanical irritation to trachea resulting
      in pain,cough,and increase in secretion after termination of the general
      anesthesia sometimes occurs and it sometimes causes hyperventilation resulting in
      hypocapnea. Continuous hypocapnea sometimes causes appearance of ischemic attacks
      in moyamoya disease. In the present study, we examine cerebral angiography
      conducted under general anesthesia using face mask ventilation in fourteen
      children with moyamoya disease. Sevoflurane was used as inhalation anesthetics.
      Face mask anesthesia was sixteen times in total in the 14 patients. Cerebral
      angiography terminated uneventfully in these patients except one patient who
      showed bronchospasm after induction of anesthesia and required tracheal
      intubation. However, the patient showed uneventful course after termination of
      the angiography. Tracheal irritation did not appear and all the patients were
      asleep just after termination of face mask anesthesia except for the patient who
      required tracheal intubation. In the latter case, the patient frequently coughed
      out phlegm after general anesthesia with tracheal intubation. In conclusion,
      general anesthesia with face mask ventilation was thought to be one of the
      suitable anesthetic methods introduced for cerebral angiography in childhood
      moyamoya disease.

PMID- 16440695
TI  - [Intraoperative ultrasonography in AVM surgery].
AB  - Intraoperative ultrasonography was used for the surgical resection of
      arteriovenous malformations in three cases. In the first case, intraoperative
      ultrasonography clearly demonstrated residual micro-AVM, which had seemed to be
      resected completely during surgery. In the second case, diminished flow of the
      draining vein by clipping of the feeding artery was demonstrated by
      ultrasonography. In the third case, intraoperative ultrasonography revealed
      stasis of the flow in the varix by clipping of the feeding artery. Intraoperative
      ultrasonography is easy to use and less expensive compared with intraoperative
      digital subtraction angiography or MRI and it is also effective for identifying
      AVMs as well as the flow patterns of the feeding arteries or draining veins.
      Intraoperative ultrasonography is a useful device for AVM surgery.

PMID- 16440696
TI  - [Orbital schwannoma developing from the superior branch of the oculomotor nerve-
      case report].
AB  - Orbital schwannoma accounts for 1-6% of all orbital tumors and it is not easy to
      identify the origin of the tumor because of the anatomy of the orbit. A case of
      orbital schwannoma developing from the superior branch of the oculomotor nerve is
      reported. A 74-year-old female was admitted to our hospital with the chief
      complaint of left exophthalmus. MR imaging revealed a space-occupying lesion in
      the left orbit. Operation was performed through the transcranial approach. It was
      noticed that the tumor was developing from the nerve that runs into the superior
      rectus muscle or the levator palpebrae superioris muscle, and it was diagnosed as
      a schwannoma on frozen section histology during surgery. The tumor was
      successfully removed and, postoperatively, no additional defects occurred.
      Careful consideration of microsurgical anatomy is essential for surgery of
      orbital schwannoma especially when it's necessary to cut the nerves.

PMID- 16440697
TI  - [Hyperkalemia caused by intravenous administration of mannitol in a patient with
      arteriovenous malformation: case report].
AB  - We experienced a case in which hyperkalemia was induced by mannitol
      administration. The medication with mannitol was given to a 15-year-old male
      patient who underwent a removal operation for arteriovenous malformation under
      general anesthesia. Following the mannitol infusion, his arterial blood gas and
      electrolyte analysis revealed severe metabolic acidosis and an increase in serum
      potassium. Furthermore, a change in his electrocardiogram was observed. The
      hyperkalemia was quickly normalized by medication with calcium gluconate and
      sodium bicarbonate. We stopped the removal operation with the aim of giving
      priority to the patient's safety. It is speculated that the hyperkalemia was
      caused by the administration of mannitol. Checks of electrolyte levels, arterial
      blood gas analysis and electrocardiogram monitoring should therefore be carried
      out when using mannitol, especially in an emergency situation such as
      intracranial hemorrhage.

PMID- 16440698
TI  - [Resolution of migraine with aura by removing pilocytic astrocytoma of the
      occipital lobe].
AB  - Migraine is one of the symptoms frequently encountered in daily neurological and
      neurosurgical clinical work. Here we report a case of pilocytic astrocytoma in
      the right occipital lobe presenting as migraine with aura. A 20-year-old female
      was referred to our hospital with the complaint of a migraine with visual aura.
      Her symptom did not respond to medical treatment. MRI of the brain disclosed a
      tumor involving the right occipital lobe. Total removal of the tumor (pilocytic
      astrocytoma, WHO grade 1) relieved her migraine completely. It has been
      previously reported that brain tumors are associated with migraine. But this is
      the first report of occipital pilocytic astrocytoma presenting as migraine with
      aura. As for other brain tumors manifesting migraine, all of them had focal
      neurological deficits or symptoms associated with increased intracranial pressure
      (ICP). The present case stresses the significance of exploration of brain tumor,
      or other organic abnormalities, even in patients suffering from migraine without
      neurological deficits or increased ICP symptoms.

PMID- 16440699
TI  - [Microvascular decompression for refractory neurogenic hypertension: case
      report].
AB  - It is noted that the increased central sympathetic nerve activity caused by
      neurovascular compression at the rostral ventrolateral medulla (RVLM) is closely
      related to the genesis of neurogenic hypertension. The authors present the case
      of a 49-year-old female with refractory neurogenic hypertension to be
      uncontrolled even with all kinds of oral antihypertensive medications. After
      approval by the Ethical Committee in a hospital, she had received an intravenous
      introduction of calcium antagonist and beta-blocker at home for three years. The
      subsequent examination detail showed increased sympathetic nerve activity and
      compression of the left vertebral artery (VA) at the left RVLM on magnetic
      resonance imaging, and therefore microvascular decompression (MVD) underwent
      through a left lateral suboccipital approach. The left VA was seen indenting the
      left RVLM. To ensure the complete decompression, the distal part of VA was moved
      away from RVLM to fix to the dura of the petrous bone with a glue. Her blood
      pressure became normalized afterwards without drugs and remained normotensive for
      23 months after MVD. In order to decide the surgical indication for pure
      neurogenic hypertension due to neurovascular compression, a strict differential
      diagnosis is necessary.

PMID- 16440700
TI  - [Choroid plexus tumors: report of 7 cases in a single institution].
AB  - The management of seven patients with choroid plexus tumors, 4 adults and 3
      children (mean age 17.5 years) at our institution was reviewed. There were 4
      cases of papilloma and 3 of carcinoma located in the lateral ventricle in 1 case,
      the third ventricle in 1 case, and the fourth ventricle in 5 cases. Total
      surgical excision was attempted in all patients. Total resection was achieved in
      three patients, resulting in no deficit in two and persistence of preoperative
      dysphagia in one. There was no recurrence after total resection. Subtotal
      resection was achieved in four patients, one of whom underwent second surgery
      resulting in total resection, and one patient died of respiratory disturbance
      after the third operation because of regrowth of the tumor. Complete excision
      could not be achieved in 3 of the 5 tumors located in the fourth ventricle
      because of extension to the brainstem. The median survival was 59.5 months for
      patients with papilloma, and 67.7 months for those with carcinoma. Adjuvant
      therapy was also required for carcinoma, one patient was treated by radiotherapy,
      and two by radiotherapy plus chemotherapy. Only one patient with papilloma was
      treated by radiotherapy plus chemotherapy postoperatively.

PMID- 16440701
TI  - [Airway management for patient safety: preface and comments].
AB  - Maintenance of patent airway has an essential role in respiratory management. The
      management of difficult airway is one of problems associated with the maintenance
      of airway patency. "Cannot intubate, cannot ventilate (CICV)" scenario is rare,
      but it usually leads to serious morbidity and mortality related to anesthesia. A
      wide variety of equipments and anesthetic techniques can be used to deal with
      this emergency situation. However, the recent practice of airway management seems
      to be very complex, depending on the introduction of new airway devices including
      laryngeal mask airway (LMA). In order to provide the reader with valuable
      information as to the new devices and airway-associated problems, five experts in
      this field contributed to this special issue of difficult airway problems.

PMID- 16440702
TI  - [Recent advances in airway management devices].
AB  - As a variety of new airway devices has been introduced, the practice of airway
      management has seemingly become more complex. Among them laryngeal mask airway
      (LMA) is the single most important development in the past 10 years. It has
      become a commonly accepted device for routine and rescue airway management, and
      is now listed in the American Society of Anesthesiologists (ASA) Difficult Airway
      Management Algorithm as an airway and a conduit for tracheal intubation. The ASA
      Task Force on Management of the Difficult Airway recommends us to have a portable
      storage unit that contains specialized equipment including LMA for difficult
      airway management. This article focuses on several of the newly developed and the
      ordinary devices that are listed by the Task Force, with particular emphasis on
      the difficult airway. Recent information about standardization work of ISO for
      rigid laryngoscopes, tracheal tubes and supralaryngeal airway devices are also
      discussed. Each airway devices has unique properties that may be advantageous in
      certain situations but disadvantageous in others. Choice and combination of
      device based on experienced clinical judgment may be crucial to their
      application.

PMID- 16440703
TI  - [Cannot intubate, cannot ventilate: airway management of difficult airways in
      adults].
AB  - Cannot intubate, cannot ventilate (CICV) is one major cause of death associated
      with general anesthesia and thus proper airway management plans are necessary. To
      achieve safe airway management, it is necessary first to predict if the patient's
      trachea can be difficult to intubate or the lungs difficult to ventilate. When
      difficulty is predicted, the following factors should be considered: (1) if
      general anesthesia is truly necessary; (2) if tracheal intubation is mandatory;
      (3) if muscle relaxation is required; (4) if awake intubation is safer; (5) if
      surgical airway is required; and (6) if tracheal intubation can prevent airway
      obstruction. When CICV occurred after general anesthesia, it is important to
      remember that the primary task is to oxygenate the patient, and not to intubate
      the trachea: the patient may need to be awaken, surgical airway obtained, or
      cardiopulmonary bypass established. To make a right decision, it is necessary to
      know the advantages and disadvantages of each option, as well as of each airway
      device, and to be acquainted with these devices during routine anesthesia. In
      this article, I will present six typical cases of difficult airways, and will
      discuss appropriate options for safer airway management.

PMID- 16440704
TI  - [Management of difficult pediatric airway].
AB  - Anesthesiologists should be familiar with the management of airway and be able to
      recognize and identify potential difficult airway. These entities include
      congenital craniofacial deformities with micrognathia (e.g. Robin sequence,
      Treacher Collins, Goldenhar's, Crouzon's syndromes) and metabolic diseases
      causing the deposit of accumulated by-products (e.g., Hurler's, Morquio's,
      Beckwith-Wiedemann syndromes). Cormack and Lehane grades 3 and 4 at laryngoscopy
      are an indication for advanced techniques for intubation. The laryngeal mask
      airway (LMA) and fiberscope with a directable tip are useful and important
      modalities in handling difficult pediatric airway and intubation. LMA not only
      offers another mode of securing airway besides face mask and tracheal intubation,
      but also provides a conduit for tracheal intubation and a rescue airway in the
      CICV (cannot intubate, cannot ventilate) situations. Intubation with a fiberscope
      can be utilized through LMA or through a specially designed face mask. Face mask
      designed for fiberoptic intubation has a 15 mm port for connection with the
      breathing circuit and another 22 mm port covered with a rubber membrane through
      which the fiberscope is introduced and directed to the larynx and trachea
      followed by the tracheal tube while ventilating and anesthetizing the pediatric
      patients with inhalational anesthetics. Getting used to these two modalities, LMA
      and fiberoptic intubation of the trachea, gives a great advantage in handling of
      difficult pediatric airway and intubation.

PMID- 16440705
TI  - [Quality assurance in airway management: education and training for difficult
      airway management].
AB  - Respiratory problem is one of the main causes of death or severe brain damage in
      perioperative period. Three major factors of respiratory problem are esophageal
      intubation, inadequate ventilation, and difficult airway. The wide spread of
      pulse oximeter and capnograph reduced the incidences of esophageal intubation and
      inadequate ventilation, but the difficult airway still occupies the large portion
      in the causes of adverse events during anesthesia. "Practice guideline for
      management of the difficult airway" was proposed by American Society of
      Anesthesiologists (ASA) in 1992 and 2002. Improvement of knowledge, technical
      skills, and cognitive skills are necessary for the education and training of the
      difficult airway management. "The practical seminar of difficult airway
      management (DAM practical seminar)" has been cosponsored by the Japanese
      Association of Medical Simulation (JAMS) in the 51 st and 52 nd annual meetings
      of Japanese Society of Anesthesiologists and the 24th annual meeting of Japanese
      Society for Clinical Anesthesia. The DAM practical seminar is composed of the
      lecture session for ASA difficult airway algorithm, the hands-on training session
      for technical skills, and the scenario-based training session for cognitive
      skills. Ninty six Japanese anesthesiologists have completed the DAM practical
      seminar in one year. "The DAM instructor course" should be immediately prepared
      to organize the seminar more frequently.

PMID- 16440706
TI  - [Problems and complications in airway management by endotracheal intubation and
      laryngeal mask airway].
AB  - The endotracheal intubation and laryngeal mask airway confer many advantages for
      surgical patients. However, a number of problems and complications with airway
      management by endotracheal intubation and laryngeal mask airway have been
      documented. In this report, several problems by using endotracheal intubation
      (e.g. hoarseness, arytenoids dislocation) and laryngeal mask airway (e.g.
      aspiration, oropharyngeal leak, gastric distension) are summarized.

PMID- 16440707
TI  - [Preoperative sedation with dexmedetomidine in patients with aneurysmal
      subarachnoid hemorrhage].
AB  - BACKGROUND: Dexmedetomidine could be beneficial for preoperative sedation of
      patients with aneurysmal subarachnoid hemorrhage (SAH) because of its sympathetic
      suppressive effect without respiratory depression. METHODS: Thirteen patients
      were sedated with continuous intravenous administration of dexmedetomidine (group
      D) and 13 were with intermittent intravenous administration of diazepam and
      pentazocine (group C). RESULTS: Blood pressure (BP) and heart rate (HR) on
      admission to OR in group D were lower than those in group C. On tracheal
      intubation, BP and HR increased in both groups, but the differences between the
      values before and after the intubation were larger in group C than in D.
      CONCLUSIONS: Preoperative dexmedetomidine infusion is suitable for patients with
      SAH.

PMID- 16440708
TI  - [Prophylactic use of droperidol for postoperative nausea and vomiting following
      gynecological laparoscopic surgery under total intravenous anesthesia].
AB  - BACKGROUND: Propofol and droperidol decrease the incidence of postoperative
      nausea and vomiting (PONV). We investigated the incidence of PONV after total
      intravenous anesthesia (TIVA) with propofol alone versus combined use of
      droperidol and propofol. METHODS: Eighty three patients, who had undergone
      laparoscopic gynecologic surgery with TIVA using propofol and fentanyl, were
      retrospectively evaluated whether droperidol had affected the incidence of early
      (up to six hours postoperatively) and late (6-24 hours postoperatively) PONV.
      Group D (46 patients) received droperidol intravenously at the end of surgery.
      Group N (37 patients) received no droperidol. RESULTS: The incidences of early
      nausea were 27% in Group N and 4% in Group D (P<0.01). The incidences of early
      vomiting were 0% in Group N and 8% in Group D. The incidences of late nausea were
      14% in Group N and 13% in Group D. The incidences of late vomiting were 3% in
      Group N and 7% in Group D. CONCLUSIONS: Droperidol was useful in reducing the
      incidence of early nausea and vomiting after total intravenous anesthesia with
      propofol and fentanyl in the patients undergoing laparoscopic surgery.

PMID- 16440709
TI  - [Anesthetic management with propofol for pheochromocytoma resection under
      monitoring of bispectral index and blood volume].
AB  - In two patients, pheochromocytoma resection was performed under propofol/fentanyl
      anesthesia, while bispectral index (BIS) monitoring and blood volume measurement
      using pulse spectrophotometry were done. In one patient (Case 2), arterial blood
      concentrations of propofol were measured by high performance liquid
      chromatography (HPLC), and compared with those of the estimated blood
      concentrations. Continuous infusion of nitroprusside and bolus infusion of
      nicardipine and/or diltiazem were used when hypertension and tachycardia
      occurred. After resection of the tumor, propofol dosage was reduced keeping the
      BIS values around 60. In both patients, blood volume was maintained higher than
      normal value (Case 1: 79-101, and Case 2: 91-112 ml x kg(-1)) during operation.
      After tumor resection, the blood pressure was maintained well without rapid
      infusion of fluid or vasopressor. Arterial blood concentration of propofol was
      lower than the estimated blood concentration during operation in high blood
      volume case (Case 2). BIS monitoring and blood volume measurement are useful for
      adjustment of propofol dosage and for avoidance of hypotension after
      pheochromocytoma resection.

PMID- 16440710
TI  - [Perioperative management for laparoscopic repair of congenital duodenal
      atresia].
AB  - BACKGROUND: Laparoscopic surgery has been applied even to neonates. To examine
      the safety and efficacy of laparoscopic repair of neonatal congenital duodenal
      atresia, we compared the 5 laparoscopic cases with the 5 conventional surgical
      cases. METHODS: The charts were retrospectively reviewed to investigate the
      anesthetic management, perioperative status and complications in the most recent
      5 cases each of laparoscopic and conventional surgeries. RESULTS: There was a
      tendency to avoid laparoscopic repair in the patients with congenital heart
      disease. There were no intraoperative complications in both groups. Laparoscopic
      group exhibited less blood loss but longer operation time. In the two out of five
      laparoscopic cases re-operation was required due to technical issues, and the
      group needed a longer period before starting enteral feeding and longer
      hospitalization. CONCLUSIONS: Up to this time, laparoscopic repair of congenital
      duodenal atresia exhibited few advantages over conventional open repair.

PMID- 16440711
TI  - [First report of malignant hyperthermia which occurred during laparoscopic
      surgery in Japan in a patient with typical family history].
AB  - We experienced a case of fulminant malignant hyperthermia during laparoscopic
      surgery, which is the first reported case of this kind. A 69-year-old man,
      weighing 69 kg, underwent laparoscopic colectomy for cecal colon cancer. He had a
      remarkable familial history of malignant hyperthermia (MH). His uncle had MH from
      enflurane. In addition, 6 male relatives died at operation, exercise or drinking.
      However, he hid it intentionally because of social concern about inheriting
      abnormal genes and of inadequate explanation from medical personnel. Anesthesia
      was induced with fentanyl 100 microg, propofol 60 mg and vecuronium 9 mg
      intravenousely and maintained with nitrous oxide, oxygen and sevoflurane. About
      120 min after the induction of anesthesia (50 min after pneumoperitoneum), PETCO2
      increased to 54 mmHg. Thirty min later, body temperature (BT), heart rate (HR),
      PETCO2 and airway pressure (Paw) increased rapidly to 37.5 degrees C, 92 beats x
      min(-1), 62 mmHg and 3/33 cmH2O, respectively. The diagnosis of MH was made. The
      inspiratory gas was changed to 100% O2, and a bolus of 100 mg dantrolene was
      given. He had BT of 39.7 degrees C, HR of 152 beats x min(-1), PETCO2 of 123
      mmHg, Paw of 3/40 cmH2O at the worst point. Rise in Paw and arrhythmia turned up
      frequently as complications of laparoscopic surgery, but they are very similar to
      the first symptoms of malignant hyperthermia. The decrease in BT with CO2
      pneumoperitoneum can mask symptoms of MH. Awareness of this fact is important not
      to delay the diagnosis.

PMID- 16440712
TI  - [Prolonged respiratory depression after fentanyl administration in a patient with
      mitochondrial encephalomyopathy].
AB  - A 21-year-old man with mitochondrial encephalomyopathy underwent surgery for
      removal of a maxillary cyst. During the induction of anesthesia, the patient fell
      into the state of apnea after intravenous administration of fentanyl 100
      microgram. Trachea was successfully intubated followed by propofol 50 mg without
      any muscle relaxants. Anesthesia was maintained uneventfully under sevoflurane (1
      2%), nitrous oxide (30%), and oxygen (70%). The respiratory depression lasted for
      about 120 minutes after administration of fentanyl, and was antagonized by
      naloxone 40 microgram. This case suggests that careful administration of fentanyl
      is mandatory in a patient with mitochondrial encephalomyopathy.

PMID- 16440713
TI  - [Facial edema and pruritus after intravenous injection of midazolam].
AB  - Midazolam is a short-acting benzodiazepine commonly used for conscious sedation
      for a variety of procedures. Severe adverse reactions, including respiratory
      depression, respiratory arrest, and anaphylactoid reaction, have been described
      by manufacturers. We report a patient who developed facial edema after iv
      injection of midazolam during caesarian section. A 26-year-old woman with a
      history of atopy and pollen allergy was scheduled for caesarian section. Spinal
      anesthesia was induced with bupivacaine without significant medical problems.
      Shortly after receiving 2 mg of iv midazolam 15 minutes after delivery for
      conscious sedation, she developed pruritus and severe facial edema. Airway
      obstruction did not occur and no specific medical treatment was necessary.
      However she was not able to open her eyes for 8 hours because of severe eyelid
      swelling. We should be more careful in administering midazolam which is generally
      regarded as safe and well tolerated.

PMID- 16440714
TI  - [Total gastrectomy of gastric stump carcinomas is more invasive than usual total
      gastrectomy for gastric carcinomas].
AB  - BACKGROUND: It is said that total gastrectomy of gastric stump carcinomas is more
      invasive than usual total gastrectomy for gastric carcinoma. METHODS: We compared
      the duration of the surgeries, blood loss, transfusion, and postoperative
      complications between patients having undergone total gastrectomy of gastric
      stump carcinomas (Group A, N=9) and those having undergone usual total
      gastrectomy for gastric carcinomas without remarkable preoperative complication
      (Group B, N=9). RESULTS: The surgical duration of Group A was significantly
      longer than that of Group B. The amount of blood loss was larger in Group A than
      in Group B. Postoperative severe complications occurred more often in Group A
      than in Group B. CONCLUSIONS: This study showes that total gastrectomy of gastric
      stump carcinomas is more invasive than usual total gastrectomy without
      preoperative complications. This seems to have been caused by adhesion of organs
      around the rest stomachs and carcinomas were very likely to be advanced ones in
      Group A. We should take the findings into considerations for maximum surgical
      blood order schedule (MSBOS) and prevention of severe postoperative complications
      in group A apart from group B.

PMID- 16440715
TI  - [Ilioinguinal nerve block during general anesthesia for inguinal herniorrhaphy in
      adult anticoagulated patients].
AB  - Two adult anticoagulated patients after valve replacement were scheduled for
      inguinal herniorrhaphy. For inguinal herniorrhaphy in adults, spinal anesthesia
      is a common anesthetic method. In order to avoid spinal hematoma due to spinal
      anesthesia, however, we employed general anesthesia combined with ilioinguinal
      nerve block. Following induction of anesthesia, a laryngeal mask airway was
      inserted. Ilioinguinal nerve block was performed with 0.25% bupivacaine 20ml.
      Ilioinguinal nerve block was effective for maintaining hemodynamic stability
      throughout the operation, and decreased postoperative pain. This technique
      appears to be a simple and safe method for providing effective and long-lasting
      perioperative analgesia following inguinal herniorrhaphy in adult patients.

PMID- 16440716
TI  - [Severe pulmonary hypertension during double lung transplantation].
AB  - We report a case of severe intraoperative pulmonary hypertension during double
      lung transplantation. A 31-year-old woman with severe primary pulmonary
      hypertension underwent double lung transplantation. Although a marked increase in
      pulmonary arterial pressure (180/80 mmHg) exceeding the level of systemic
      arterial pressure occurred after anesthetic induction, the operation could be
      performed with scheduled cardiopulmonary bypass without using urgent percutaneous
      cardiopulmonary support.

PMID- 16440717
TI  - [Laryngeal mask application for a case of unpredictable adult tracheal stenosis].
AB  - A 69-year-old man with chronic renal failure was scheduled for artero-venous
      shunt surgery for sustained hemodialysis. On the pre-anesthesia interview, the
      patient complained of no respiratory symptom. Chest x-ray showed some tracheal
      deviation. There was no past history of the respiratory system such as
      bronchitis, bronchial asthma, tumor, trauma or previous tracheal intubation.
      General anesthesia was induced smoothly with thiopental and suxamethonium. Face
      mask ventilation could be done easily. The vocal cord was exposed fully by
      standard McIntosh laryngoscope. However, a neither ID 7.5 nor 6.5 mm tracheal
      tube could be inserted into the trachea. Then, a size 4.0 laryngeal mask airway
      (LMA) was inserted smoothly and ventilation was maintained adequately. The
      surgery was done smoothly. Seven days after, bronchofiber scopic findings showed
      tracheal stenosis. The cause was unknown but not from inflammation or tumor. The
      patient complained no respiratory distress after the surgery. In such
      unpredictable tracheal stenosis with easy mask ventilation, LMA is a considerable
      option for respiratory management.

PMID- 16440718
TI  - [Anesthetic management of a child with Noonan syndrome and hypertrophic
      obstructive cardiomyopathy].
AB  - Noonan syndrome is characterized by facial, skeletal and cardiovascular
      anomalies. We describe the anesthetic management of a one-year-old boy with
      Noonan syndrome and hypertrophic obstructive cardiomyopathy scheduled for
      tonsillectomy and adenoidectomy under general anesthesia. He had a history of
      congestive heart failure at 5 months of age. Preoperative echocardiogram revealed
      a hypertrophied septum (12.8 mm) with concentric hypertrophy of the left
      ventricle. Mild mitral regurgitation was also noted. Our anesthetic goal was set
      to maintaining adequate preload and afterload as well as adequate anesthesia
      depth to avoid LV outflow tract obstruction. Intravenous fluid was started the
      day before surgery. Anesthesia was induced with fentanyl 30 microg and midazolam
      2 mg and maintained with propofol 8 mg x kg(-1) x hr(-1), fentanyl 30 microg,
      ketamine 4 mg, and sevoflurane 1-2%. Intraoperative monitoring included 12-lead
      electrocardiogram and direct measurement of arterial pressure. Intra- and post
      operative course was uneventful.

PMID- 16440719
TI  - [Case in which landiolol hydrochloride improved left ventricular outflow tract
      obstruction with systolic anterior motion of the mitral valve following mitral
      valve plasty].
AB  - We report a case of left ventricular outflow tract (LVOT) obstruction caused by
      systolic anterior motion of the mitral valve (SAM) following mitral valve plasity
      (MVP). A 65-year-old man underwent mitral valve plasty for grade III mitral valve
      regurgitation. The plasty was done smoothly and the patient was weaned from
      cardiopulmonary bypass successfully with continuous dobutamine infusion. However,
      about 30 minutes after the weaning, severe cardiovascular collapse developed.
      Inotropic agent, such as dobutamine, ephedrine, or calcium hydrochloride was not
      effective. Trans-esophageal echocardiography (TEE) showed severe mitral valve
      regurgitation with LVOT obstruction due to SAM. The collapse was successfully
      treated with volume loading and a small amount of a beta1-adrenergic antagonist,
      landiolol hydrochloride. We conclude that acute LVOT obstruction with SAM could
      develop following MVP. TEE was a much useful tool for early diagnosis and
      landiolol hydrochloride would be a notable agent for nonsurgical treatment of
      LVOT obstruction with SAM.

PMID- 16440720
TI  - [Difficulty in one-lung ventilation reveals tracheobronchial anomaly].
AB  - A 57-year-old man with carcinoma of the esophagus was scheduled for a subtotal
      esophagectomy. We used a bronchial blocker tube to perform one-lung ventilation
      (OLV). But the OLV was not feasible because of a tracheobronchial anomaly of the
      right superior lobe bronchus. We replaced the bronchial blocker tube with a
      standard double lumen tube, and the OLV thus became complete. When we cannot
      perform a complete OLV with a bronchial blocker tube, we should consider the
      possibility of a tracheobronchial anomaly. When one is found in the right
      superior lobe bronchus, we should use a standard double lumen tube to perform the
      OLV.

PMID- 16440721
TI  - [Anesthetic management of laser surgery with bronchial stenting for a tracheal
      tumor].
AB  - Anesthetic management during surgery for a tracheal tumor is extremely difficult
      in terms of airway management. We managed a patient with a tracheal tumor who was
      successfully treated without complication. The trachea of a 66-year-old woman was
      narrowed by a tumor to one-third of its original diameter, for which Nd-YAG laser
      surgery with insertion of an intratracheal Dumon stent was performed. Anesthesia
      was maintained with neuroleptanalgesia using fentanyl and droperidol,
      supplemented with a TCI infusion of propofol under spontaneous breathing. High
      frequency jet ventilation (HFJV) was prepared for intraoperative poor oxygenation
      and/or ventilation. The patient was able to maintain a good respiratory condition
      throughout the operation without special respiratory support, including use of
      HFJV. We conclude that the maintenance of spontaneous breathing is essential for
      anesthetic management in the present case, while an intraoperative airway
      strategy based on the preoperative breathing condition of the patient is also
      important.

PMID- 16440722
TI  - [Anesthetic and perioperative management of patient for breast reconstruction in
      an outpatient clinic].
AB  - BACKGROUND: Our clinic provides various reconstructive surgeries but does not
      have facilities for patient admission, but there is a hospital providing
      satisfactory post-operative treatments in our area. METHODS: During the past 3
      years, 276 patients received reconstructive mammoplasty under general anesthesia
      at our clinic. Their post-operative conditions immediately after the recovery
      were evaluated with the Modified Post-Anesthesia Discharge Scoring System
      (MPADSS). After observation for 4 to 5 hours in a recovery room, all the patients
      were transferred to another hospital by car. RESULTS: The score was 9 or 10
      points in 45% of the patients. This indicates that the patients can be
      transferred to another hospital without problems. Twenty percent of patients had
      6-7 points. These patients had mild bleeding, pain and/or
      unsteadiness/nausea/vomiting while walking. Among the 256 patients who were
      transferred to another hospital by car, one patient vomited in the car and 5
      patients had nausea after the transfer. The other 20 patients whose score was 7
      or lower were transferred by special vehicle with a stretcher and their
      conditions did not aggravate at all. CONCLUSIONS: At present, it is dangerous to
      perform all breast reconstructive surgeries as a day surgeries. A system is
      indispensable in which patients are transferred after surgery to another hospital
      with over-night stay facilities enabling observation.

PMID- 16440723
TI  - [Clinical experience of laparoscopic adrenalectomy: the National Defense Medical
      College experience].
AB  - Twenty-seven laparoscopic adrenalectomies (LapAdx) were performed at the National
      Defense Medical College between 1999 and 2004. We evaluated the results of LapAdx
      (group L) compared to the results of open adrenalectomy (group O). Twenty-six of
      the 27 LapAdx were successfully performed, but one patient with a large
      pheochromocytoma required open surgey because of arterial bleeding in the renal
      hilus. The mean operating time in group L (185 +/- 19 min) was not significantly
      different from that in group O (206 +/- 13 min). The mean estimated blood loss in
      group L (111 +/- 61 g) was significantly lower than that in group O (308 +/- 67
      g). The starting time for oral feeding and for ambulation was significantly
      earlier in group L than in group O. There was a major complication
      (intraoperative bleeding) in which a group L patient required a blood
      transfusion. We also compared the surgical results of 26 patients in LapAdx
      divided chronologically into the first half and the last half to determine the
      surgical skill acquired. The operating time was significantly shorter and blood
      loss significantly less for patients in the last half. In addition, the operating
      time and blood loss for the first-time LapAdx operators were comparable with
      those of experienced surgeons. Our results support the efficacy and the minimal
      invasiveness of LapAdx. The accumulated experience and knowledge regarding
      laparoscopic surgery in our institute were important in improving surgical
      procedures and results.

PMID- 16440724
TI  - [Chemo-endocrine therapy for newly diagnosed stage D2 prostate cancer].
AB  - We evaluated 175 patients with newly diagnosed stage D2 prostate cancer who had
      been treated in our hospital between 1992 and 2003 to compare chemo-endocrine
      therapy with endocrine therapy alone. One hundred and thirty seven patients were
      treated with endocrine therapy alone. The other 38 patients received chemo
      endocrine therapy, which included medical or surgical castration with/without
      antiandrogen plus VIP (Vincristine, Ifosfamide, Peplomycin) regimen or other
      cytotoxic agents. The patients treated with chemo-endocrine therapy had a
      significantly better prognosis than the patients treated with endocrine therapy
      alone (p<0.05), although treatment was not randomized. The cause-specific
      survival rates at 5 years for the chemo-endocrine therapy group and the endocrine
      therapy group were 61.6% and 34.8%, respectively. These data suggest that chemo
      endocrine therapy is a potentially effective treatment for newly diagnosed stage
      D2 prostate cancer.

PMID- 16440725
TI  - [Pheochromocytoma associated with neurofibromatosis 1: a report of two cases].
AB  - Pheochromocytomas may occur as either sporadic or familial tumors. Clinical
      features of pheochromocytomas in neurofibromatosis 1 (NF1) patients are similar
      to those in patients with sporadic pheochromocytomas, unlike pheochromocytomas
      associated with other hereditary syndromes. Here we report two cases of
      pheochromocytoma associated with NF1. Case 1: A 29-year-old man with previously
      undiagnosed NF1, was admitted to our hospital for hypertension and a right
      adrenal tumor. On physical examination, cafe-au-lait spots and neurofibromas were
      observed on his body. Serum and urine catecholamine levels were markedly
      elevated. Case 2: The patient was a 46-year-old man with NF1. The tumor was
      incidentally detected by ultrasonography. Serum and urine catecholamine levels
      were similarly elevated. 131I-MIBG scintigraphy showed an abnormal accumulation
      in the right adrenal gland. After this diagnosis of pheochromocytoma associated
      with NF1, open adrenalectomy was performed. No evidence of malignancy was seen in
      either case.

PMID- 16440726
TI  - [Spontaneous rupture of renal angiomyolipoma: a case report].
AB  - A 55-year-old woman presented with sudden right lower abdominal pain. Computed
      tomography demonstrated retroperitoneal hematoma associated with minus-density
      area, diagnosed as spontaneous rupture of angiomyolipoma. Super-selective
      transarterial embolization was performed, but anemia and right abdominal pain
      became worse in spite of conservative therapy including transfusion, indicating
      re-rupture of the renal tumor. Although partial nephrectomy was planned, right
      nephrectomy was finally performed because of massive intraoperative bleeding.
      Accurate diagnosis and prompt treatment are required when life-threatening
      rupture of renal tumor is suspected.

PMID- 16440728
TI  - [Three cases of pulmonary hamartoma appearing after radical nephrectomy for renal
      cell carcinoma].
AB  - We report 3 patients with pulmonary hamartoma, all of whom had undergone
      nephrectomy for renal cell carcinoma. A lung tumor was detected 2 to 9-months
      following nephrectomy. Preoperative diagnosis was pulmonary metastasis from renal
      cell carcinoma and pulmonary tumor resection was performed in each case. There
      was a 9- to 12-month interval between the detection and resection of the lung
      tumor. The histological diagnosis of the lung tumor in all three patient was
      pulmonary hamartoma. Following the resection of the lung tumor, recurrence was
      not noted in any of the patients.

PMID- 16440727
TI  - [A case of pyonephrosis with septic shock in a hemodialysis patient treated
      successfully by retroperitoneal drainage].
AB  - A 56-year-old man on long-term hemodialysis was admitted to our hospital with
      complaints of right back pain and low-grade fever. Physical examination and
      laboratory data revealed severe hypotension and coagulopathy. Abdominal computed
      tomography showed a low dense area at the back of the right atrophic kidney.
      Under the clinical diagnosis of pyonephrosis spreading around the kidney with
      septic shock and disseminated intravascular coagulation, we performed drainage of
      retroperitoneal abscess. General condition improved postoperatively and right
      nephrectomy was performed two weeks after the drainage.

PMID- 16440729
TI  - [Ureteral polyp resected with a ureteroscope: report of two cases].
AB  - Two cases of ureteral polyp resected by a transurethral approach are presented.
      Case 1: A 70-year-old woman was referred to our clinic because of hydronephrosis
      incidentally found. Excretory urography demonstrated a filling defect with a long
      and round smooth contour in the left lower ureter without hydroureter. Urine
      cytology was negative for malignant cells. Under the clinical diagnosis of left
      ureteral polyp, polyp was resected transurethrally. The pathological diagnosis
      was fibroepithelial polyp. Case 2: A 59-year-old woman was referred to our clinic
      with a chief complaint of macroscopic hematuria. Excretory urography revealed a
      filling defect with a long and round smooth contour in the left upper ureter.
      Because urine cytology was negative for malignant cells, left ureteral polyp was
      suspected. After the operation by tranthurethral approach, the pathological
      diagnosis was fibroepithelial polyp. No intraoperative complication was observed
      in either case. Ureteral polyps resected by a transurethral approach are
      relatively rare. We reviewed and discussed 46 cases of ureteral polyp resected
      transurethrally, reported in Japan including our two cases.

PMID- 16440730
TI  - [A rare case of transitional cell carcinoma of the ileum segment arising 43 years
      after ureteroileocystoplasty due to tuberculous bladder atrophy].
AB  - A 60-year-old woman visited our hospital complaining of fever up. She had
      undergone augmentation ileoplasty for tuberculous bladder atrophy 43 years age.
      Cystoscopy revealed a broadbased tumor on the ileal segment. Histopathological
      findings of the biopsy specimen demonstrated grade 3 transitional cell carcinoma.
      She was given 2 courses of chemotherapy (methotrexate, vincristine, adriamicin,
      cisplatin), but died of metastasis of carcinoma 4 months after diagnosis.

PMID- 16440732
TI  - [A case of Sertoli cell tumor].
AB  - We report a case of Sertoli cell tumor. A 33-year-old man visited our clinic with
      a complaint of painless left scrotal swelling on September 29th, 2003. An elastic
      firm induration larger than a hen's egg in size was palpable on the surface of
      the left testis. Tumor markers for testicular tumor such as human chorionic
      gonadotropin-beta, alpha fetoprotein, and lactate dehydrogenase were not
      elevated. However, ultrasound showed a low echoic mass in the left testis.
      Therefore, we performed left high orchiectomy under the diagnosis of left
      testicular tumor. Its histology showed Sertoli cell tumor. Neither recurrence nor
      metastasis has been detected for about 8 months after the operation.

PMID- 16440731
TI  - [A case of emphysematous cystitis].
AB  - A 60-year-old woman visited our clinic with a complaint of gross hematuria. She
      was under treatment for rheumatoid arthritis, amyloidosis and diabetes mellitus
      at the Departments of Orthopedic Surgery and Internal Medicine. The results of a
      urine analysis showed protein urine, glucose urine, hematopyuria and bacteriuria.
      The diagnosis of emphysematous cystitis was made from radiography, ultrasonogram
      and cystoscopic findings. Antibiotics were administered effectively. However, one
      month later, bilateral hydronephrosis was identified by a computed tomographic
      scan performed by the Department of Internal Medicine. The bilateral
      hydronephrosis was brought on by urinary retention caused by a neurogenic bladder
      disorder. Thus, an indwelling catheter followed by intermittent catheterization
      was performed and cholinergic medication prescribed successfully.

PMID- 16440733
TI  - [A case of primary and solitary bone metastasis of testicular seminoma after
      orchiectomy].
AB  - A 40-year-old man with stage I left testicular seminoma who had been followed for
      18 months after orchiectomy, complained of pain in his left upper extremity and
      dysbasia. Magnetic resonance imaging (MRI) and bone scintigraphy suggested
      multiple bone lesions in the thoracic vertebrae and right ischium, and bone
      biopsy revealed metastasis of seminoma. There was no evidence of other metastatic
      lesions. After he was treated with 2 courses of first-line chemotherapy
      consisting of peplomycin, etoposide, and cisplatin, which were followed by 2
      courses of high-dose chemotherapy with carboplatin, etoposide, and ifosfamide,
      the metastatic lesions were nearly in complete response on MRI and bone
      scintigraphy and the result of fluorodeoxyglucose-positron emission tomography
      was negative, but the hCG-beta level remained slightly elevated. In most advanced
      testicular tumors, bone metastasis usually coexists with other metastatic lesions
      and appears as a secondary lesion. Herein, we report this rare case of primary
      and solitary bone metastasis from testicular seminoma after orchiectomy.

PMID- 16440735
TI  - [Retroperitoneal lymph node recurrence of seminoma 6 years after high
      orchiectomy].
AB  - Late recurrence of stage I testicular seminoma is rare. We herein report a case
      of retroperitoneal lymph node recurrence of testicular seminoma 6 years after
      high orchiectomy. A 39-year-old man had a left high orchiectomy for stage I
      testicular tumor in November 1997. Histopathological findings revealed seminoma
      (pT3). In 2003, follow up computed tomography showed retroperitoneal lymph nodes
      swelling. Serum tumor markers had been normal since 1997. Retroperitoneal lymph
      nodes were dissected in April 2004. Histopathological findings were recurrence of
      seminoma.

PMID- 16440734
TI  - [Aortic replacement during post chemotherapy retroperitoneal residual tumor
      resection for nonseminomatous germ cell tumor: a case report].
AB  - A 59-year-old man visited our hospital complaining of epigastralgia. A large hard
      mass was palpable in the abdominal cavity. Abdominal computed tomography revealed
      large retroperitoneal cystic tumors. His left testis was hard and swollen. Under
      the diagnosis of testicular tumor and retroperitoneal lymph node metastasis, left
      radical orchiectomy was performed and the histopathological examination showed
      mature teratoma. He was diagnosed with nonseminomatous germ cell tumor and
      retroperitoneal lymph node metastasis (TNM classification stage IIC). He received
      three cycles of chemotherapy with bleomycin, etoposide, and cisplatin and we
      performed retroperitoneal residual tumor resection. Because the tumor tightly
      adhered to the aortic wall, abdominal aorta was resected and replaced by an
      artificial vessel. The post-operative course was uneventful. Histopathological
      diagnosis was cystopapillary adenocarcinoma and mature teratoma. The patient is
      well 1 and a half years after the operation without recurrence.

PMID- 16440736
TI  - [Bilateral tuberculous epididymitis after intravesical Bacillus Calmette-Guerin
      therapy].
AB  - We describe a case of bilateral tuberculous epididymitis that occurred two weeks
      after intravesical Bacillus Calmette-Guerin (BCG) instillation. A 72-year-old man
      received transuretheral resection of bladder transitional cell carcinoma in
      November 2000. Although he had no recurrence for about 4 years, cystoscopy
      revealed small papillary tumors in the bladder in September 2004. A course of 8
      weekly intravesical instillations of BCG was started. After the second BCG
      instillation (160 mg) he had bilateral painful scrotal swelling. Although he was
      administered isoniazid (INH) and rifampicin (RFP), scrotal swelling got worse.
      Right orchiectomy and left epididymectomy was performed in December 2004.
      Histological diagnosis was bilateral tuberculous epididymitis. Postoperatively,
      he was administered INH and RFP and had no recurrence for 3 months.

PMID- 16440737
TI  - [A case of prostatic stromal tumor of uncertain malignant potential].
AB  - Sarcomas and related proliferative lesions of specialized prostatic stroma are
      rare. Lesions have been classified into prostatic stromal tumor of uncertain
      malignant potential (P-STUMP) and prostatic stromal sarcoma based on the degree
      of stromal cellularity, presence of mitotic figures, necrosis, and stromal
      overgrowth. STUMPs are considered neoplastic, based on the observations that they
      may diffusely infiltrate the prostate gland and extend into adjacent tissues, and
      often recur. Although most cases of STUMPs do not behave in an aggressive
      fashion, occasional cases have been documented to recur rapidly after resection
      and a minority have progressed to stromal sarcoma. Here we describe a case of P
      STUMP. A 57-year-old male went to his family doctor because of pollakisuria.
      Digital examination revealed abnormal findings in the prostate, then he was
      referred to our medical center. The mass was palpable in the left lobe of the
      prostate; it was elastic hard, surface smooth, about 2 cm in diameter. Serum PSA
      was elevated slightly (5.42 mg /dl). We diagnosed firstly leiomyosarcoma by
      transrectal ultra sound guided needle biopsy of the prostate. Then we performed
      radical prostatectomy. Finally we made the pathological diagnosis of P-STUMP.
      After 11 months, there is no sign of metastasis or recurrence.

PMID- 16440738
TI  - [Antiapoptotic functions of the retrovirally transferred API2-MALT1 gene].
AB  - t(11 ; 18)(q21 ; q21) is a specific chromosomal aberration in mucosa-associated
      lymphoid tissue (MALT) lymphoma, and produces chimeric transcript Apoptosis
      Inhibitor 2 (API2)-MALT1. Although it is known that API2 has an antiapoptotic
      effect, it is still unclear whether this also applies to API2-MALT1. To
      investigate its effects against various apoptotic stimuli, API2-MALT1 was
      expressed by means of retroviral infection on the epithelial cell line HeLa and
      the murine Pro-B cell line Ba/F3. On both these cell lines, API2-MALT1 was found
      to cause a significant reduction in UV-induced apoptosis. The apoptosis induced
      by doxorubicin was also inhibited by API2-MALT1, but not that induced by IL-3
      withdrawal from Ba/F3. These findings suggest that API2-MALT1 has an
      antiapoptotic effect on both epithelial and lymphoid cells and that this effect
      depends on the apoptotic stimulus.

PMID- 16440739
TI  - [Unclassified mature T cell leukemia with cerebriform nuclei].
AB  - A 53 year-old male visited our hospital for evaluation of his leukocytosis, which
      was first diagnosed more than 6 years previously. He was asymptomatic and there
      were no remarkable findings on physical and laboratory examinations except for
      the lymphocytosis. Abnormal lymphocytes with deep folded nuclei were seen on
      light microscopy, whose phenotype was CD3+, CD4-, CD8-, CD7-, CD16 , CD56-,
      CD45RO+ and CD45RA- . Electron microscopy revealed 'cerebriform nuclei' which
      were characteristic of Sezary cells. Adult T cell leukemia (ATL) and Sezary
      syndrome (SS) were ruled out because of the negative HTLV-1 test and the absence
      of skin lesions, respectively. T-prolymphocytic leukemia (T-PLL), which is
      characterized by a marked increase in leukocytes having a CD7-phenotype and a
      progressive fatal course, was also excluded. Recently, the TCL1 onco-protein has
      been shown to be overexpressed in progressive T-PLL but not in other mature T
      cell leukemias including Sezary syndrome. Peripheral mononuclear cells in the
      present patient did not overexpress TCL1. In its morphology and phenotypes, our
      case resembled 'Sezary cell leukemia (SCL)' but the clinical course was much more
      indolent. This case did not match any of the mature T cell leukemias defined in
      the WHO classification.

PMID- 16440740
TI  - [Diffuse large B-cell lymphoma expressing surface immunoglobulin heavy chain (Ig
      alpha) and lacking light chains].
AB  - A 59-year-old woman with goiter complained of nausea, vomiting and weight loss in
      April 2000. She underwent an endoscopic examination and was admitted to our
      hospital because gastric biopsy specimens revealed that she had diffuse large B
      cell lymphoma. A thyroid biopsy also detected the diffuse infiltration of
      lymphoma cells, which were positive for CD19, CD20, CD38 and HLA-DR. Although the
      cells expressed surface immunoglobulin a chain, they lacked expressions of the
      kappa and lambda light chains. Chromosomal analysis of the thyroid cells showed
      47, XX, t(2 ; 3)(q31 ; q13), + 3, t(8 ; 22)(q24 ; q11). After five courses of
      biweekly CHOP chemotherapy, she received autologous peripheral blood stem cell
      transplantation in October 2000. Currently, she has maintained complete remission
      for more than 4 years.

PMID- 16440741
TI  - [Triple secondary malignancy of gingiva, palate and esophagus after an allogeneic
      bone marrow transplantation for cutaneous T-cell lymphoma].
AB  - A 31-year-old man was diagnosed as having cutaneous T-cell lymphoma in January
      1994. He received an allogeneic bone marrow transplantation (BMT) from an HLA
      matched sibling donor in May 1995, because of refractoriness to chemotherapy. The
      patient had been treated with immunosuppressants including prednisolone and
      cyclosporin A for chronic graft-versus-host disease (GVHD) of the extensive type
      following acute GVHD. Five years after the BMT, he developed moderately
      differentiated squamous cell carcinoma (SCC) on the mandibular gingival mucosa
      and underwent surgical resection. Furthermore, 6 years after the BMT well
      differentiated SCC developed on his palate and was resected. Concurrently, he was
      diagnosed as having esophageal cancer (poorly differentiated SCC) and underwent a
      subtotal esophagotomy. One year later he had a recurrence of the esophageal
      cancer with dysphagia and was treated with radiation and chemotherapy. He remains
      free of triple cancer and lymphoma. It is suggested that total body irradiation,
      immunosuppressants, and chronic GVHD are associated with a risk of secondary
      malignancies following allogeneic BMT. These factors might have contributed to
      the onset of triple cancer in our patient.

PMID- 16440742
TI  - [CD30-negative diffuse large B-cell lymphoma expressing ALK].
AB  - A 33-years-old man was diagnosed as having undifferentiated carcinoma presenting
      with right neck lymphadenopathy in December 2000. He obtained complete remission
      (CR) following chemotherapy, radiation and lymphadenectomy on the right neck. He
      had multiple para-aorta lymphadenopathy and splenomegaly in December 2001. An
      open-abdominal lymph node biopsy was performed from which a diagnosis of
      anaplastic large cell lymphoma was made. CR was achieved with biweekly CHOP,
      however, the patient suffered from a relapse twice. He underwent allogeneic
      peripheral blood stem cell transplantation (PBSCT) from his HLA-matched sister
      while in non-CR in November 2002. Engraftment was achieved on day 14, and at the
      same time, complete chimerism was confirmed. Acute grade III graft-versus-host
      disease (GVHD) developed and was controlled with cyclosporine A and prednisolone.
      Extensive chronic GVHD was subsequently observed and required systemic
      immunosuppression. His condition returned to CR after the PBSCT and he sustained
      complete chimerism. He suddenly died of fulminant thrombotic microangiopathy
      seven months after the PBSCT. The tumor cells were ALK-positive, CD30-negative
      and JH rearrangement was detected, and were therefore classified as diffuse large
      B-cell lymphoma with expression of ALK according to the WHO classification,
      though they differed from this subtype in some points. Although this case was
      refractory for chemotherapy with a complex karyotype, the graft-versus-lymphoma
      effect might have contributed to the sustained CR following the PBSCT.

PMID- 16440743
TI  - [Soft tissue amyloidoma].
AB  - A 59-year-old man was referred to our hospital for the evaluation of pain on
      exertion of the right arm. X-ray examination showed a humeral tumor, and a
      tumorectomy was subsequently performed. The histological analysis showed necrotic
      tissue with no malignant cells. Serum protein electrophoresis yielded a small
      amount of M proteins without monoclonality of immunoglobulins. The bone survey in
      the whole body showed lucency of the right humerus, vertebra, ribs, left femur,
      skull, and right scapla. During outpatient clinic observation, a computed
      tomography scan of the pelvis showed a painless large tumor in the gluteus,
      appearing as an amyloidoma. Soft tissue amyloidoma occur very rarely, and so we
      here report a case of a soft tissue amyloidoma in the gluteus with review of the
      literatures.

PMID- 16440744
TI  - [Refractory Evans syndrome complicated with transverse sinus thrombosis].
AB  - A 29-year-old woman was diagnosed as having Evans syndrome in 2002 and underwent
      a splenectomy for the refractory status of the disorder in May 2004. One and a
      half months after the operation, her platelet count again decreased due to
      relapse, and she was then prescribed with high dose dexamethasone (38 mg/day x 4
      days). Five days after the medication, she complained of a severe headache and
      then fell into coma, even though her platelet count had risen to 8 x 10(4)/mm3.
      Computer tomography scan of the brain showed severe edema with a massive
      hemorrhage in left temporooccipital lobe, which was compatible with cerebral
      transverse sinus thrombosis. After resection of the damaged brain, her level of
      consciousness gradually recovered, although visual disturbance and moderate
      hemiplegia remained. This is the fourth case of idiopathic thrombocytopenic
      purpura which was complicated with sinus thrombosis in the literature.

PMID- 16440745
TI  - [Effective treatment for a methotrexate-associated lymphoproliferative disorder
      with R-CHOP following administration of rituximab].
AB  - A 65-year-old male had a two-month history of fever and fatigue. He had been
      receiving low dose MTX administration for about 2 years for rheumatoid arthritis.
      The blood chemistry findings showed elevated liver function including lactic
      dehydrogenase (LDH) levels. The quantified serum EBV-DNA level was 200 copies/105
      peripheral blood mononuclear cells. Computed tomographic scan demonstrated
      splenomegaly and intraperitoneal mass lesions. One of the masses was biopsied.
      Some tumor cells showed a large Hodgkin cell-like appearance. These were CD3e-,
      CD20 +, CD30 +, CD15-, LMP1 +, EBNA2-, EBER-ISH + without imbalance of the
      kappa/lambda ratio. A diagnosis of MTX-associated B-lymphoproliferative disorder
      was made. Although the patient's fever subsided and the serum LDH levels were
      normalized after withdrawal of the MTX, the masses showed almost no change.
      Therefore, we administered rituximab weekly for a total of four doses, resulting
      in normalization of the serum EBV-DNA load and serum CD4/CD8 ratio. The masses
      persisted, however, so we carried out eight courses of R-CHOP therapy, which
      induced complete response without any episode of serious infection.

PMID- 16440746
TI  - [Acute myeloid leukemia complicated with pulmonary alveolar proteinosis at
      presentation].
AB  - A 47-year-old male had symptoms of coughing and with fever and was admitted to
      our hospital where tests revealed he had anemia and thrombocytopenia. Following
      the results obtained from a bone marrow aspiration, he was diagnosed as having
      acute myeloid leukemia (AML). A chest radiograph and a CT scan demonstrated
      nodular shadows and pleural exudate in both lungs. We suspected atypical
      pneumonia, or fungal pneumonia, and he was subsequently given antibiotics and
      antifungal agents, which were, however, ineffective. On the third day after
      admission, he was put on mechanical ventilation, and a bronchoalveolar lavage
      examination revealed no germs. His respiration, however, progressively worsened
      and he died on the twelfth day after admission. Although the autopsy findings
      revealed no infectious lesions in his lungs, a PAS-positive intra-alveolar
      eosinophilic material, which was positive for surfactant apoprotein A staining,
      was present. As a result of the autopsy findings, a diagnosis of secondary
      pulmonary alveolar proteinosis (PAP) associated with AML was made. Among the
      reported cases of PAP in hematological malignancy, there has not been one case
      detected at the time AML was diagnosed. If there is evidence of an unknown cause
      of lung infiltration when AML is diagnosed, attention should be paid to the
      possibility of the presence of PAP.

PMID- 16440747
TI  - [Allogeneic bone marrow transplantation for chemotherapy-resistant T
      prolymphocytic leukemia].
AB  - A 34-year-old female was referred to our hospital for the evaluation of atypical
      lymphocytosis. Leukocyte count at diagnosis was 17,900/microl with 58% atypical
      lymphocytes having a convoluted nucleus and prominent nucleoli. Because the
      leukocyte count increased to 43,600/microl, the patient was treated with
      2'deoxycoformycin followed by CHOP combination chemotherapy. However, both
      treatments failed to achieve remission. We planned an allogeneic bone marrow
      transplantation from an HLA-matched unrelated donor. The patient was treated with
      Ara-C and etoposide before conditioning to decrease the high leukemia burden.
      After administration of total body irradiation (12 Gy in six fractions) and
      cyclophosphamide (total dose of 120 mg/kg) unmanipulated marrow cells were
      infused. Under prevention of GVHD by CsA and short-term MTX, leukocyte engraft
      was prompt at day 16, and acute GVHD grade II was observed. Because 9.4% of
      residual recipient type T-cells was seen with STR analysis on day 22, we
      decreased the dose of Cs'A. After the occurrence of mild acute GVHD, the residual
      T-cell number decreased. The patient is still in complete remission for up to 22
      months after BMT. We conclude that allogeneic SCT is effective for the treatment
      of T-PLL.

PMID- 16440748
TI  - [Persistent neutrophilia occurring after pneumonia: a differential diagnosis of
      neutrophilia based on the WHO classification].
AB  - We experienced a 85-year-old female patient with granulocytosis, which occurred
      after the bacterial pneumonia. The white blood cell counts remained high between
      30,000/microl and 120,000/microl for around one year. As the serum G-CSF level
      was within the normal range and there were no tumors on CT scan images, the
      existence of G-CSF-producing solid tumors was unlikely. Bone marrow examination
      revealed hypercellularity without excess of blasts and hiatus leukemia,
      accompanied by mild dysplasia in myeloid cells and megakaryocytes. No chromosomal
      abnormalities in bone marrow samples were seen with G-banding and multi-color
      FISH methods. Major/minor BCR-ABL fusion genes were negative by RT-PCR. As
      previously reported by several investigators, we often experience difficulties in
      distinguishing atypical CML from CNL and CMML. In this report, we discussed how
      to diagnose the cause of granulocytosis based on a literature review.

PMID- 16440749
TI  - [Successful treatment with CHOP therapy for progressive of primary
      macroglobulinemia without further increase of serum IgM].
AB  - A 61-year-old man with primary macroglobulinemia (PMG) had been followed without
      any treatment as he had no apparent manifestations. After 1 year and 3 months, he
      was admitted to our hospital with a fever. No signs or symptoms of infection and
      no progressive increase of serum IgM levels was observed. Non-Hodgkin's lymphoma
      was not additionally found. Fever without infection, elevated serum LDH level and
      further enlargement of the spleen compelled us to diagnose his condition as
      deterioration of the PMG. An immediate fall in his temperature and serum IgM
      levels was observed after CHOP therapy. Effective therapy must be discussed in
      the deterioration of this type of disease.

PMID- 16440750
TI  - [Mechanisms underlying odorant and pheromone reception].

PMID- 16440751
TI  - [Molecular mechanism that inhibits axon regeneration].

PMID- 16440752
TI  - [The world of RNA modifications; another topics of functional RNAs].

PMID- 16440753
TI  - [Construction history of bispecific antibodies and overview of its application
      for cancer immunotherapy].

PMID- 16440754
TI  - [Trans-splicing in living cells].

PMID- 16440755
TI  - [Enzymes involved in the biosynthesis and degradation of anandamide].

PMID- 16440756
TI  - [Identification of the target molecules for galectin family].

PMID- 16440757
TI  - [N-glycan structures of avian IgG/IgY].

PMID- 16440758
TI  - [Designing functional siRNA sequences].

PMID- 16440759
TI  - Thirty-three years of the Federation of Asian and Oceanian Biochemists and
      Molecular Biologists (FAOBMB) (1972-2005).

PMID- 16440760
TI  - [Evaluation of prophylactic use of lamivudine in HBV-positive patients with
      malignant lymphoma undergoing chemotherapy].
AB  - A prospective evaluation was carried out on the effect of lamivudine
      administration as a prophylactic measure to prevent exacerbation of hepatitis in
      HBV carrier or chronic hepatitis B patients with malignant lymphoma undergoing
      chemotherapy. Eighteen patients were registered between 1997 and 2002 from
      institutions of the Research Group for the Treatment of Malignant Lymphoma. The
      patients' median age was 53 years old (39-73), and consisted of 8 males and 10
      females. HBe-seroconversion had already occurred in 13 and liver biopsy had been
      performed in 8. No adverse effects of lamivudine were noted and the serum HBV-DNA
      content did not increase during lamivudine administration. Planned treatment
      courses could be completed in all patients. In 2, however, the viral load
      increased and the HBe antibody (Ab) value declined after the cessation of
      lamivudine, which were reversed to the normal ranges following the resumption of
      lamivudine. As for the overall outcome, 14 of the patients survived, and there
      were 4 fatalities due to malignant lymphoma. Serum HBeAb status may be regarded
      as a useful laboratory marker for deciding the safe cessation of lamivudine. An
      additional case is described, who had recovered from past HBV infection, but
      eventually succumbed to fulminant hepatitis after the cessation of lamivudine
      covering prolonged courses of chemotherapy. This illustrates a need for inclusion
      of such cases for the prophylactic use of lamivudine.

PMID- 16440761
TI  - [Acute myelogenous leukemia with mediastinal and subcutaneous emphysema following
      chronic GVHD after allogeneic bone marrow transplantation].
AB  - A 38-year-old man was diagnosed as having acute myelogenous leukemia in December
      2001. He achieved a complete remission after undergoing three courses of
      induction chemotherapy. As the patient's prognosis was considered to be poor, he
      was then treated with a bone marrow transplant from his HLA 1 antigen mismatched
      sister in May 2002. Grade 2 skin graft-versus-host-disease (GVHD) developed on
      day 14 but reduced with methylprednisolone (mPSL). Prednisolone (PSL) was
      discontinued on day 104, and the patient was discharged on day 112. There was no
      evidence of clinical chronic GVHD, the serum creatinine level remained high, and
      cyclosporine (CsA) was gradually tapered off and discontinued on day 165. However
      chronic GVHD of the skin appeared on day 179, and CsA (100 mg/day) was restarted.
      On day 186 he was admitted to our hospital complaining of fever. A CT scan of the
      chest demonstrated bilateral interstitial infiltrates, which were considered as
      lung GVHD lesions and PSL was started, following which chronic GVHD of the skin
      and liver improved. The lung GVHD worsened, however, subcutaneous and mediastinal
      emphysema developed and the patient died on day 206. Interstitial pneumonia had
      progressively worsened as the manifestation of the chronic lung GVHD. We
      concluded that this clinical course was rare.

PMID- 16440762
TI  - [Therapy-resistant microcytic hypochromic anemia from malabsorption-related
      vitamin B6 deficiency after a gastrointestinal operation].
AB  - We present a case of a 33-year-old man, who had a past history of a total
      pancreatectomy for duodenal malignant lymphoma complicated by life-threatening
      bleeding during chemotherapy at 23 years of age. He achieved complete remission
      and received no more chemotherapy. Around August 1999 he developed anemia, which
      failed to improve following intravenous administration of iron, and he was
      hospitalized. The cause of the anemia remained unclear and he received a blood
      transfusion. Because of the increasing frequency of transfusions, he was admitted
      to our hospital to evaluate his anemia in September 2000. On examinations,
      laboratory findings revealed a low level of serum vitamin B6 (B6) with iron
      deficiency. Intravenous administration of B6 was performed in addition to iron,
      with the result that the patient's hemoglobin level was kept at 10 g/dl without
      blood transfusion. An oral B6 administration test resulted in a low level of B6.
      These results suggest that B6 deficiency due to malabsorption may cause therapy
      resistant anemia. Some reports say that B6 deficiency causes microcytic
      hypochromic anemia, since B6 is necessary for erythrocytic hemopoiesis as a
      coenzyme for heme biosynthesis. In the case of microcytic hypochromic anemia, if
      the cause is unclear, evaluation should be performed, taking the possibility of a
      hidden cause of B6 deficiency into consideration.

PMID- 16440763
TI  - [Pulmonary tuberculosis and adenovirus-hemorrhagic cystitis after autologous
      peripheral blood stem cell transplantation for follicular lymphoma].
AB  - A 58-year-old man had a relapsed follicular lymphoma (Grade 2) and was treated
      with mitoxantrone, fludarabine and dexamethasone followed by rituximab, and
      achieved partial remission. The patient then underwent high-dose chemotherapy
      followed by autologous peripheral blood stem cell transplantation (auto-PBSCT).
      Three days after starting high-dose therapy, he developed a fever, and a chest X
      ray revealed pneumonia in the right lower lung. Despite of the administration of
      antibiotics and the recovery of neutrophils to normal levels, the pneumonia got
      worse. Bronchoalveolar lavage (BAL) was performed on day 32, the Ziehl-Neelsen
      staining of the BAL fluid showed acid-fast bacilli, and the culture grew
      Mycobacterium tuberculosis. The patient was diagnosed as having pulmonary
      tuberculosis and placed on an antituberculosis regimen (isoniazid, rifampicin,
      ethambutol, pyrazinamide). On day 43 he also developed hemorrhagic cystitis due
      to adenovirus type 11, and on day 49 positive CMV antigenemia was detected, which
      were treated supportively. On day 75 he developed pneumonia probably due to
      Pneumocystis jirovecii, which was treated with sulfamethoxazole/trimethoprim. The
      pulmonary tuberculosis resolved completely 4 months after starting the treatment,
      and the hemorrhagic cystitis and pneumocystis pneumonia resolved 1 month after
      the diagnosis. He remains in complete remission 2 years after transplantation.

PMID- 16440764
TI  - [Early transformation from follicular lymphoma to Burkitt lymphoma].
AB  - We report a rare case of follicular lymphoma which rapidly showed transformation
      to the Burkitt type of lymphoma after a treatment consisting of chemotherapy and
      irradiation. A 51-year-old male visited our hospital in August 2000 because of
      bilateral neck lymphadenopathy. He was diagnosed as having follicular lymphoma
      (grade 2) (clinical stage IIIA) with complex karyotypic abnormalities involving
      t(14 ; 18)(q32 ; q21) and CD20 expression. Initially he was followed as an
      outpatient without chemotherapy. Six months later, he was admitted because of
      hydronephrosis due to an intrapelvic tumor. He underwent chemotherapy with 4
      courses of CHOP regimen following irradiation therapy and a partial response was
      obtained. Four months after initiation of the treatment, his disease recurred
      with numb chin syndrome. Bone marrow aspiration revealed bone marrow involvement
      by lymphoma cells which had a Burkitt-like appearance. A cytogenetic study using
      bone marrow blood showed complex abnormalities involving t(8 ; 22)(q24 ; q11) in
      addition to t(14 ; 18). In spite of salvage chemotherapy, the patient died in
      September 2001.

PMID- 16440765
TI  - [Intestinal bleeding during the treatment of chronic myeloid leukemia with
      imatinib mesylate].
AB  - A 35-year-old woman attended our hospital with chronic myeloid leukemia and was
      prescribed imatinib mesylate. She was admitted with lower abdominal pain,
      stomatitis, and hyposthenia after an increase in her dose of imatinib mesylate.
      When the treatment was changed to interferon-alpha and Ara-C, the lower abdominal
      pain, stomatitis, and hyposthenia improved, but bone marrow aspiration showed
      36.4% blasts. After the treatment was changed back to an increased dose of
      imatinib mesylate (800 mg), the stomatitis deteriorated and intestinal bleeding
      reoccurred. Endoscopy demonstrated the presence of multiple ulcers in the
      ascending colon and 99mTc RBC scintigraphy demonstrated lesions of the large and
      small intestine. The patient declined any treatment except for transfusion and
      died suddenly after ten days. The present case suggests that we should carefully
      consider the possibility of intestinal bleeding when prescribing imatinib
      mesylate.

PMID- 16440766
TI  - [Angioimmunoblastic T-cell lymphoma occurring four months after autologous
      peripheral blood stem cell transplantation with high-dose chemotherapy for
      follicular lymphoma].
AB  - A 62-year-old Japanese woman was diagnosed as having follicular lymphoma (FL,
      grade 3, CS IIIA, IPI high-intermediate risk) in May 1998. After eight courses of
      CHOP therapy, she achieved a complete remission (CR). In November 1998, her FL
      relapsed, and she achieved a second CR after two courses of MINE therapy. High
      dose etoposide was used for autologous peripheral stem cell mobilization. In May
      1999, she underwent high-dose chemotherapy with autologous peripheral blood stem
      cell transplantation (auto-PBSCT). Four months after the auto-PBSCT, bilateral
      cervical lymphadenopathy developed. Histopathological findings from a biopsied
      cervical lymph node showed angioimmunoblastic T-cell lymphoma (AILT). The patient
      was treated with modified CVP therapy, and she is alive with no evidence of
      lymphoma five years after auto-PBSCT. Clinical and histopathological findings
      showed that the FL and AILT in this case were not concomitant. It is thought that
      in this case, the AILT developed as a post-transplant lymphoproliferative
      disorder after auto-PBSCT for the FL.

PMID- 16440767
TI  - [Bronchoesophageal fistula in a patient with untreated malignant lymphoma].
AB  - Bronchoesophageal fistulae associated with lymphomas are generally associated
      with chemo-radiotherapy. We report here an unusual case of lymphoma with a
      therapy-unrelated bronchoesophageal fistula. Previously, only 10 similar cases
      have been reported. A 70-year-old male was diagnosed as having gastric diffuse
      large B-cell lymphoma in May 1998. In January 1999, he noted a cough after eating
      and drinking. Because of the presence of a febrile temperature, productive cough
      and dyspnea, he was referred to our hospital and diagnosed as having aspiration
      pneumonia. Antibiotics did not improve his symptoms. When tracheal intubation was
      performed with bronchoscopy, a bronchoesophageal fistula was revealed. Malignant
      lymphoma cells were found around the fistula in the biopsy specimen. The patient
      died of pneumonia after treatment with airway stenting and chemotherapy.
      Induction of necrosis by chemotherapy or low blood flow with stenting and
      dopamine probably caused enlargement of the fistula.

PMID- 16440768
TI  - [Successful salvage therapy of continuous low-dose irinotecan for a patient with
      relapsed and refractory diffuse large B-cell lymphoma].
AB  - A 46-year-old man with relapsed and refractory diffuse large B-cell lymphoma
      after salvage therapy (EPOCH and ESHAP regimens) was treated with continuous low
      dose CPT-11 (irinotecan hydrochloride) at 30 mg/day (20 mg/m2/day) for three
      consecutive days every week. The patient's general condition and both LDH and
      CRP, tumor related markers, improved dramatically. Complete remission was
      achieved after a 10-week cycle of therapy without severe adverse effects.
      Unfortunately, the lymphoma relapsed after allogeneic hematopoietic stem cell
      transplantation, low-dose CPT-11 therapy was used again to palliate tumor
      symptoms for 12 months. This therapy may be a useful salvage and palliative
      chemotherapy for relapsed and refractory lymphoma.

PMID- 16440769
TI  - [Hematopoietic stem cell transplantation in the second or later complete
      remission in acute promyelocytic leukemia initially treated with all-trans
      retinoic acid].
AB  - Despite the use of all-trans retinoic acid (ATRA) as the first-line treatment for
      acute promyelocytic leukemia (APL), relapse occurs in about 20% of cases. Most
      relapsing APL patients can achieve second remission (CR2) following ATRA combined
      with chemotherapy or arsenic trioxide. Stem cell transplantation (SCT) has been
      widely adopted in CR2, but optimal SCT (auto- or allo-SCT) remains controversial.
      We analyzed the outcomes for 8 APL patients initially treated using ATRA, who
      relapsed, achieved CR2 and underwent auto-SCT (n = 4) or allo-SCT (n = 4). The
      mean age of patients who underwent allo-SCT was 39 years. Minimal residual
      disease (MRD) just prior to SCT was positive in 1 patient and negative in 3.
      Engraftment was achieved in all patients, but 2 patients died of transplantation
      related complications within 6 months. Complete molecular remission has been
      maintained in the remaining 2 patients. The mean age of patients who underwent
      auto-SCT was 48 years. MRD just prior to SCT was negative in all 4 patients.
      Complete molecular remission has been maintained in all 4 patients (mean follow
      up, 3 years 9 months). The results for auto-SCT are favorable in patients with
      MRD-negative APL.

PMID- 16440770
TI  - [Cyclosporine A as an effective treatment for a patient with acquired hemophilia
      A complicated with diabetes mellitus and ischemic heart disease].
AB  - Acquired hemophilia A (AHA) is a rare coagulation disorder due to the development
      of an autoantibody against and inhibitor of coagulation factor VIII. It has been
      reported that immunosuppressive therapy with corticosteroids, cyclophosphamide,
      azathioprine and vincristine are effective to decrease this inhibitor. When
      corticosteroids and cytotoxic drugs are ineffective, cyclosporine A (CyA) may be
      effective as a second-line salvage therapy. Except for postpartum conditions, AHA
      usually occurs in elderly patients who are often already suffering from diabetes
      mellitus, ischemic heart disease and/or hyperlipidemia. However,
      immunosuppressive and cytotoxic drugs may have adverse effects on these patients.
      We report on a 66-year-old man who developed AHA after colon cancer resection
      (factor VIII inhibitor: 61 Bethesda units/ml, aPTT : 97.9 s). Since he already
      had both diabetes mellitus and ischemic heart disease, we abandoned treatment
      with corticosteroids and oral cyclophosphamide was started, but was switched to
      CyA because of leukopenia. Within 3 months of starting the CyA treatment, aPTT
      levels returned to normal and 4 further months were required for complete
      eradication of the inhibitor. This case revealed that CyA is as effective as
      corticosteroids for AHA. For patients with AHA who have unfavorable complications
      due to corticosteroids and cytotoxic drugs, CyA could be a potential first-line
      drug.

PMID- 16440771
TI  - [Long-term remission after CHOP therapy in a case of multifocal extranodal
      diffuse large B-cell lymphoma with t(1 ; 14) (p22 ; q32) and rearrangement of bcl
      10].
AB  - The translocation t(1 ; 14)(p22 ; q32) has been reported only in cases of mucosa
      associated lymphoid tissue (MALT) lymphomas. Moreover, bcl-10 is a novel
      apoptotic signaling gene located at 1p22 and t(1 ; 14)(p22 ; q32) may directly
      expose bcl-10 to Ig somatic hypermutation. A recent report indicates a pathogenic
      role of bcl-10 mutation in the progression of MALT lymphomas. In this report, we
      describe the first case of multiple extranodal diffuse large B-cell lymphoma
      (DLBCL) with t(1 ; 14)(p22 ; q32). A 70-year-old woman was diagnosed as having
      DLBCL of multiple extranodal sites (lung, duodenum, colon and kidney).
      Cytogenetic analysis of a renal lesion revealed the chromosome translocations t(1
      ; 14)(p22 ; q32) and both IgH and bcl-10 gene rearrangements were confirmed by
      Southern blot hybridization. The patient received a regimen of cyclophosphamide,
      doxorubicin, vincristine and prednisone (CHOP). She achieved complete remission
      after six cycles of chemotherapy and has been free of disease for more than five
      years. This is the first case of bcl-10 gene rearrangement in DLBCL with t(1 ;
      14)(p22 ; q32) and this gene may be involved in the pathogenesis of aggressive
      lymphomas such as MALT lymphomas or in the progression of MALT lymphomas.

PMID- 16440772
TI  - [Effective treatment with rituximab in two patients with Waldenstrom
      macroglobulinemia].
AB  - CD20 is usually expressed on tumor cells in Waldenstrom's macroglobulinemia (WM).
      We report on two patients who achieved good responses with rituximab treatment.
      <Case 1> A 78-year-old man had anemia and was referred to our hospital in 1997.
      On admission, IgM-kappa monoclonal protein was detected in the serum and the IgM
      level was 4850 mg/dl, leading to the diagnosis of WM. In 2002, he developed heart
      failure due to anemia, and was treated with rituximab. The IgM level decreased to
      about 200 mg/dl and remained unelevated for 2.5 years. The anemia also improved.
      < Case 2 > A 59-year-old man was found to have elevated serum IgM (4850 mg/dl)
      and came to our hospital in 1998. IgM-kappa monoclonal protein was detected in
      the serum and he was diagnosed as having WM. His IgM level had been controlled
      with cyclophosphamide administration, but elevated levels were noted again in
      2004. He was given rituximab, and a partial response was obtained (IgM 995
      mg/dl).

PMID- 16440773
TI  - [Successful treatment with cyclosporine of sodium valproate-induced pure red cell
      aplasia].
AB  - We report a 67-year-old man who developed pure red cell aplasia (PRCA) during
      therapy for epilepsy with sodium valproate since April 2004. He was admitted to
      our hospital because of severe anemia (Hb 5.0g/dl, reticulocyte 0.1%) in August
      2004. A bone marrow examination showed marked erythroid hypoplasia and a
      diagnosis of drug-induced PRCA was made. Because the discontinuation of valproate
      for one month failed to increase the number of reticulocytes and frequent blood
      transfusions were necessary, cyclosporine therapy was initiated. Within a week,
      substantial recovery of the numbers of reticulocytes was obtained, the
      cyclosporine had, however, to be changed to prednisolone due to the refusal of
      the patient to continue with it, resulting in the exacerbation of his anemia.
      After three weeks, cyclosporine therapy was resumed, which achieved rapid and
      remarkable recovery of red blood cells (Hb 8.9g/dl, reticulocyte 4.9%) within one
      month. Sixteen cases of valproate-induced PRCA have been reported in the
      literature and all cases except one recovered only by discontinuing or reducing
      the administration of valproate. However, our case required cyclosporine therapy
      in addition to the discontinuation of valproate. These results suggest that not
      only the direct toxic effect on erythropoiesis but also T lymphocyte-mediated
      immunological mechanism was involved in the pathogenesis of valproate-induced
      PRCA.

PMID- 16440774
TI  - [Basedow disease associated with Evans syndrome].
AB  - A 60-year-old woman was admitted to a hospital complaining of dizziness and
      general fatigue in October, 2004. Because of heart failure and severe anemia, she
      was referred to our hospital. Based on a positive direct Coombs test and an
      elevated level of platelet-associated IgG (PAIgG), the patient was diagnosed as
      having autoimmune hemolytic anemia (AIHA) associated with idiopathic
      thrombocytopenic purpura (ITP), i.e., Evans syndrome. Basedow disease was also
      diagnosed due to hyperthyroidism with an elevation of anti-thyroid stimulating
      hormone (TSH) receptor antibodies. Both the Evans syndrome and Basedow disease
      were considerably ameliorated with plasma exchange, corticosteroid and thiamazole
      therapy. Although Basedow disease is known to be associated with hematological
      disorders such as AIHA or ITP, the combination of Basedow disease and Evans
      syndrome is rare. We report here a case of Basedow disease associated with Evans
      syndrome.

PMID- 16440775
TI  - [A woman complicated with immune thrombocytopenic purpura, subclinical Graves
      disease and peripheral neuropathy 5 years after allogeneic bone marrow
      transplantation].
AB  - A 21-year-old woman developed immune thrombocytopenia (ITP), subclinical Graves
      disease and peripheral neuropathy without typical chronic graft-versus-host
      disease (GVHD) 5 years following an allogeneic bone marrow transplantation from
      an HLA-identical sibling. She received high-dose intravenous immunoglobulin
      (IVIG) and prednisolone (PSL), which resulted in transient recovery of platelet
      numbers and muscle weakness. A combination of cyclosporine and PSL induced a
      durable response against not only the thrombocytopenia but also her high levels
      of thyroid stimulating antibody (TSAb), muscle weakness and sensory abnormality.
      The level of thyroglobulin in the donor, who had not developed Graves disease,
      was also elevated, indicating that late onset-subclinical Graves disease was
      caused by donor lymphocytes that were autoreactive to the thyroid glands.

PMID- 16440776
TI  - [Epstein-Barr virus related B-cell lymphoproliferative disorder complicated with
      bone marrow fibrosis, which was successfully treated with 2 courses of CHOP
      regimen].
AB  - A 68-year-old man was referred to our hospital in August 2003 with a high fever,
      a prominent inflammatory reaction in blood test and also bicytopenia (anemia and
      thrombocytopenia) with marked hepatosplenomegaly. He was temporarily diagnosed as
      having malignant lymphoma considering the elevated levels of LDH and soluble
      interleukin-2 receptor, following which treatment with the CHOP regimen was
      started. Thereafter, based on the pathological findings from a bone marrow biopsy
      and a quite high viral load revealed by real-time PCR analysis, the diagnosis was
      changed to Epstein-Barr virus (EBV) related B-lymphoproliferative disorder (B
      LPD) complicated with reticulin fibrosis. A total of 2 courses of the CHOP
      regimen together with anti-viral reagents almost resolved the clinical symptoms
      and abnormal findings of laboratory tests. This unique case was considered to be
      "a senile EBV positive B-LPD" complicated with a secondary myelofibrosis, a
      category of the disorder which has recently been proposed by Shigeo Nakamura at
      the Aichi Cancer Center.

PMID- 16440777
TI  - [Essential thrombocythemia associated with incomplete type intestinal Behcet
      disease during hydroxyurea treatment].
AB  - A 77-year-old man was diagnosed as having essential thrombocythemia in 1992.
      Treatment with hydroxyurea was started in 1997, which stabilized the platelet
      count. The patient then suffered from pharyngalgia and rhinitis with a high
      fever, immediately after which he developed tarry stools and anemia and was
      admitted to our hospital. The physical examination revealed splenomegaly, oral
      aphthous ulcers, genital ulcers and skin lesions on the lower limbs. His
      hematological and biochemical tests revealed anemia and increased level of C
      reactive protein. He also had an HLA-B51 phenotype. The findings of gastro
      intestinal and colon fiberoscopy showed a duodenal ulcer and multiple ulcers on
      ascending colon. He was thus diagnosed as having intestinal tract-type Behcet
      disease. After withdrawal of the hydroxyurea administration, the intestinal
      ulcers, oral aphthous ulcers and genital ulcers improved.

PMID- 16440778
TI  - [Two cases of primary skeletal muscle lymphoma, and a review of the literature].
AB  - Here we report two cases of primary skeletal muscle lymphoma. The first patient
      was an 82-year-old man. On April 2004, he was referred to our hospital because of
      swelling of the right upper arm. Magnetic resonance imaging (MRI) showed an area
      which was isointense on T1 and hyperintense on T2-weighted imaging compared with
      normal skeletal muscle. The size of the tumor was 5 x 7 x 13 cm. Following
      pathological, flow cytometric and genetic analyses of the specimen, we diagnosed
      the tumor as a non-Hodgkin lymphoma of the T-cell rich diffuse large B-cell type.
      The second patient was an 87-year-old man. He was admitted to our hospital on
      July 2004, under the chief complaint of swelling of the right thigh. MRI revealed
      a giant tumor mass of the right thigh which was isointense on T1 and hyperintense
      on T2 imaging. The patient was diagnosed by open biopsy as having diffuse large B
      cell lymphoma. We could find only 62 cases of primary skeletal muscle lymphoma
      through a MEDLINE search. We report on our two cases with a review of the
      literature.

PMID- 16440779
TI  - [Case of intraspinal epidural tumor developing after systemic mastocytosis with
      marked osteosclerosis and myelofibrosis].
AB  - A 64-year-old man was diagnosed as having urticaria pigmentosa in 1998, and
      treated with PUVA therapy. In January 2002, X-ray imaging revealed osteosclerosis
      was detected in the systemic bone and bone scintigraphy. A bone marrow aspiration
      sample was not obtained due to a dry tap. CT scans showed hepatosplenomegaly and
      mesenteric lymphadenopathy. Myelofibrosis and diffuse mast cell infiltration were
      revealed by a bone marrow biopsy, and a diagnosis of systemic mastocytosis with
      severe osteosclerosis and myelofibrosis was made. In October 2003, he was
      admitted to our hospital because of mid back pain. A neurological examination
      showed muscle weakness in the upper and lower limbs, sensory disturbance below
      the level of Th4 and urinary obstruction. T1 and T2 weighted images of MRI
      demonstrated a high intensity epidural mass lesion extending from the vertebral
      level of C5 to Th2 and severely compressing the spinal cord. We considered the
      possibility of the invasion of the spinal canal by the mastocytosis. The patient
      was treated with interferon alpha-2b (IFN-alpha2b) and prednisolone.
      Subsequently, the motor and sensory disturbances were gradually alleviated, and
      spinal MRI confirmed a marked reduction in the size of the epidural tumor.
      However, the patient became resistant to interferon, and died of multiple organ
      failure in spite of steroid pulse and cladribine therapies. Multiple organ
      infiltration by mast cells was revealed at autopsy.

PMID- 16440781
TI  - [Acquired hemophilia developing after treatment of idiopathic interstitial
      pneumonia].
AB  - A 72-year-old man was diagnosed as having idiopathic interstitial pneumonia (IIP)
      in May 1999. Immunosuppressive therapy successfully controlled the activity of
      the IIP. In February 2004, he was referred to our department because of multiple
      large hematomas. Laboratory examination revealed prolonged activated partial
      thromboplastin time (APTT; 103.4 seconds), reduced factor VIII activity (7.0%),
      and the presence of factor VIII inhibitor. Immunosuppressive therapy
      (prednisolone 1 mg/kg/day) was initiated. After 41 days, APTT decreased to 33.4
      seconds and the factor VIII inhibitor disappeared. This is the first reported
      case of acquired hemophilia which developed during treatment of IIP.

PMID- 16440780
TI  - [Psoriasis vulgaris exacerbated by imatinib therapy in chronic myelogenous
      leukemia].
AB  - Administration of imatinib exacerbated psoriasis vulgaris in a case of chronic
      myelogenous leukemia (CML). After the cessation of imatinib therapy, the
      psoriasis was alleviated. Upon readministration of imatinib, the psoriasis
      worsened despite the improvement of hematological and cytogenetic findings in the
      CML. Psoriasis is known to be an autoimmune skin disease characterized by Th1
      cell-mediated hyperproliferation of keratinocytes, and the type 1 helper T (Th1)
      cell subset increased with imatinib therapy. Thus, the exacerbation of psoriasis
      was likely due to the increase in Th1 cells associated with imatinib therapy.

PMID- 16440782
TI  - [Intracranial extramedullary hematopoiesis following bilateral chronic subdural
      hematoma in a patient with idiopathic myelofibrosis].
AB  - This is a case of remarkable intracranial extramedullary hematopoiesis (EMH) in a
      63-year-old male patient with a history of idiopathic myelofibrosis. Intracranial
      EMH was suspected following cranial computed tomography and magnetic resonance
      imaging and was found in the same sites as the bilateral subdural hematomas. The
      patient subsequently received whole brain irradiation (30 Gy). The lesion was
      controlled for one and a half years. After the patient died from bacterial
      infection, intracranial EMH was confirmed in autopsy and histological diagnoses.

PMID- 16440783
TI  - [Viral food-borne diseases caused by norovirus].

PMID- 16440784
TI  - Occurrence of paralytic shellfish poison (PSP)-producing dinoflagellate
      Alexandrium tamarense in Hiroshima Bay, Hiroshima Prefecture, Japan, during 1993
      2004 and its PSP profiles.
AB  - To assess levels of shellfish intoxication by the paralytic shellfish poison
      (PSP)-producing dinoflagellate Alexandrium tamarense, potential health risks to
      human shellfish consumers and the possible need for regulatory intervention,
      yearly variations of maximum cell density of this species were examined from 1993
      to 2004 in Kure Bay and Kaita Bay, which are located within Hiroshima Bay,
      Hiroshima Prefecture, Japan. The seawater temperature was determined
      concomitantly. In Kure Bay, maximum concentrations of 1,400 and 1,300 cells/mL at
      0 and 5 m depths were observed on 21 and 24 April 1997. In Kaita Bay, remarkably
      high concentrations above 1,000 cells/mL of A. tamarense were observed in two out
      of three years investigated. These facts suggest that the environment in both
      bays is favorable for the propagation of A. tamarense. The temperature range at
      which the natural population of A. tamarense blooms was generally from 12 to 16
      degrees C. Four strains (ATKR-94, -95, -97 and -01) from Kure Bay and one strain
      (ATKT-97) from Kaita Bay were established. The strain ATKR-94, cultured in
      modified SW-2 medium at 15 degrees C for 15 days, showed a specific toxicity of
      33.8 x 10(-6) MU/cell. The toxins in all five strains exist almost exclusively as
      beta-epimers (C2 (PX2 or GTX8), GTX3, dcGTX3 and GTX4), which accounted for 54.9
      to 73.0 mol% of the total. The corresponding a-epimers (C1 (PX1 or epi-GTX8),
      GTX2, dcGTX2 and GTX1) accounted for 6.0 to 28.9 mol%. The toxin profiles of ATKR
      97 and ATKT-97 were characterized by unusually high proportions of low-potency
      sulfocarbamoyl toxin, which comprised 62.4 and 68.2 mol%, respectively, of total
      toxins. In the toxic bivalves, the low-toxicity sulfocarbamoyl components, major
      components of A. tamarense, were present in amounts of only a few percent,
      suggesting that in vivo conversion of PSP occurs after ingestion. A comparison of
      the toxin profiles of the causative dinoflagellate and contaminated bivalves
      showed that PSP components exist in the bivalves in the form of alpha-epimers,
      presumably owing to accumulation or storage of the toxins.

PMID- 16440785
TI  - Paralytic shellfish poison (PSP) profiles and toxification of short-necked clams
      fed with the toxic dinoflagellate Alexandrium tamarense.
AB  - As a part of our studies on paralytic shellfish poison (PSP) accumulation
      kinetics in bivalves, short-necked clam Tapes japonia was experimentally
      contaminated with PSP by being fed with the toxic dinoflagellate Alexandrium
      tamarense for 2, 4, 6, 8 and 10 days, and the processes of PSP accumulation and
      bioconversion were investigated: the toxicity level was determined by mouse
      bioassay and toxin components were identified by high-performance liquid
      chromatography (HPLC). The strain of A. tamarense used in this study possessed a
      specific toxicity of 186.7 +/- 81 (mean +/- S.D., n = 5) x 10(-6) MU/cell. Total
      toxin concentration of this strain was 140.4 +/- 61 (mean S.D., n = 5) fmol/cell.
      The toxicity level of short-necked clams increased almost in parallel with the
      abundance of A. tamarense, reaching 1.8, 3.2, 3.8, 3.5 and 4.6 MU/g meat for 2,
      4, 6, 8 and 10 days of feeding, respectively. The accumulation rates of PSP
      toxins, which are the ratio of the total amount of toxins accumulated in the
      bivalves to the estimated intake in each feeding experiment, were 7.5, 8.1, 5.7,
      4.2 and 4.4% for 2, 4, 6, 8 and 10 days, respectively. At the end of each
      exposure period, many undigested algal cells were found in pseudofeces under
      microscopic observation. There was a remarkable difference in the relative
      proportions of the predominant toxin components between A. tamarense and short
      necked clams. The most notable difference was the change in the relative amounts
      of C2 (carbamoyl-N-sulfo-11beta-hydroxysaxitoxin sulfate), GTX1 and GTX 4 during
      the first two days. In the toxic bivalves, the amount of C2, which is dominant in
      A. tamarense, decreased to below half a percent after being ingested.
      Subsequently, the amount of GTX1 in the shellfish meat reached 50.1 mol%, while
      that of GTX4 decreased to about half of that in A. tamarense. As for the
      configuration of 11-hydroxysulfate, PSP components in A. tamarense exist almost
      exclusively as beta-epimers (GTX3, GTX4, C2 and C4), accounting for 72.8 mol% of
      the total. This contrasts with the case of the short-necked clams, where the beta
      epimers represented 25.8, 33.8, 30.8, 36.8 and 28.5 mol% of the total after 2, 4,
      6, 8 and 10 days, respectively. PSP components seemed to be converted rapidly at
      an early stage of the feeding of A. tamarense.

PMID- 16440787
TI  - [Method of component assay of alpha-glucosyltransferase-treated stevia
      (enzymatically modified stevia) products using enzymatic hydrolysis].
AB  - We have developed an analytical method for components of alpha
      glucosyltransferase-treated stevia, a food additive product. Suitable conditions
      to separate additional sugar from alpha-glucosyltransferase-treated stevia by
      using glucoamylase were found (55 degrees C for 3 hr with 250 U of glucoamylase
      in 10 mL of reaction solution). By solid-phase extraction using a C18 cartridge
      column, polysaccharides were excluded from the sample, and the glycosides and
      sugar obtained after hydrolysis with glucoamylase were separated on another C18
      cartridge column. The glycosides and sugar contents were determined by HPLC. By
      this method, additional sugar was detected in all of three product samples tested
      and the sugar was glucose. The contents of glucose and total glycosides (minus
      unreacted glycoside) were 25-42% and 35.7-52.5%, respectively. In alpha
      glucosyltransferase-treated stevia, the sum of total glycosides and glucose
      amounted to 77.5-80.4% of the total and their recoveries from samples from which
      polysaccharide had been excluded by C18 cartridge column processing were over
      85%. The contents of alpha-glucosyltransferase-treated stevia obtained by
      multiplying the sugar content by the coefficient (0.9) for hydrolysis and
      converting on dry weight basis were all over 80.0% and met the standard set by
      the Japan Food Additives Association.

PMID- 16440788
TI  - [Laboratory performance study of the quantitative detection method for
      genetically modified soybeans (roundup ready soybeans 40-3-2)].
AB  - To investigate important factors affecting the analytical results, a laboratory
      performance study was attempted for the Japanese official methods to detect
      genetically modified (GM) soybeans (40-3-2). Test samples containing 0, 1 and 5%
      GM soya powder in non-GM soya powder was prepared. A set of 3 test samples was
      sent to the participating laboratories along with the protocol. The data were
      collected from all laboratories and statistically analyzed. In the real-time PCR
      detection method, the average values of the GM 1% and 5% samples were both much
      lower than the spiked value because the laboratories using a silica-membrane DNA
      extraction method underestimated the GM value. On the other hand, the
      laboratories using other extraction methods, such as the CTAB method obtained
      values close to the spiked value. These results suggest that use of the silica
      membrane DNA extraction method may result in underestimation of the GM content in
      the real-time PCR method. In the ELISA method, the average value of 5% spiked
      samples appears to be slightly higher than the fortified value. But, overall, it
      was considered that reported values were close to the spiked level.

PMID- 16440786
TI  - Levels of dioxins in Japanese fruit in 1999 to 2002 and estimation of their
      intake.
AB  - A total of 148 samples of nine species of fruit were collected between 1999 and
      2002 and analyzed for PCDDs, PCDFs (PCDD/Fs) and Coplanar PCBs. Sampling points
      within about 1 km of operational municipal waste incinerators that were
      considered sources of dioxins were defined as "near-source" areas, and all other
      sampling points were defined as "general" areas. The TEQ of apples collected from
      near-source areas was significantly higher than that from general areas (p <
      0.05). 3,3',4,4',5-PeCB (#126) was the main contributor to this difference in
      TEQs between apples collected from near-source areas and from general area. A
      principal component analysis performed to estimate the source of this congener
      revealed that not only the municipal waste incinerators, but also PCBs in the
      environment were associated with the high TEQ in apples collected from near
      source areas. The daily intakes of PCDD/Fs and Coplanar PCBs from the fruits
      including skin were estimated to be 0.0082 pg-TEQ/kg b.w./day (ND = 0) and 0.072
      pg-TEQ/ kg b.w./day (ND = 1/2 LOQ). Though these values are likely to be
      overestimates, they are far lower than the tolerable daily intake set in Japan
      for PCDD/Fs and Coplanar PCBs (4 pg-TEQ/kg b.w./day). It is thought that fruit
      intake is not an important pathway of human exposure to PCDD/Fs and Coplanar
      PCBs.

PMID- 16440791
TI  - [Inter-laboratory validation studies of biological method for determination of
      tetracyclines in royal jelly].
AB  - Inter-laboratory validation studies were conducted in 5 laboratories to validate
      the biological method for determination of tetracyclines in royal jelly.
      Oxytetracycline spiked at the levels of 0.2 and 1.0 ppm was analyzed. Mean
      recoveries were 88 and 90%, reproducibility relative standard deviations (RSD(R))
      were 13.7 and 7.8%, and HORRAT(R) values were 0.7 and 0.5. Samples containing
      residues at the levels of 0.25 and 0.80 ppm were analyzed. Mean recoveries were
      73 and 77%, RSD(R) were 12.6 and 10.5%, and HORRAT(R) values were 0.6 and 0.6.
      The determination limit was 0.1 ppm (oxytetracycline, tetracycline) and 0.02 ppm
      (chlortetracycline). These results show that this method has good performance.

PMID- 16440796
TI  - [Global regulation of allergen labeling system].

PMID- 16440792
TI  - [Inter-laboratory validation studies of biological method for determination of
      streptomycin in royal jelly].
AB  - Inter-laboratory validation studies were conducted in 6 laboratories to validate
      the biological method for determination of streptomycin in royal jelly.
      Streptomycin spiked at the level of 0.2 and 1.0 ppm was analyzed. Mean recoveries
      were 89 and 96%, reproducibility relative standard deviations (RSD(R)) were 15.0
      and 14.0%, HORRAT(R) values were 0.7 and 0.9. Samples containing residues at the
      levels of 0.25 and 0.80 ppm were analyzed. Mean recoveries were 113 and 99%,
      RSD(R) were 15.0 and 10.4%, and HORRAT(R) values were 0.8 and 0.6. The
      determination limit was 0.1 ppm. These results show that this method has good
      performance.

PMID- 16440794
TI  - [Residues of total mercury and methyl mercury in eel products].
AB  - Fifty-two samples of broiled eels and broiled eel liver were analyzed for total
      mercury (total Hg) and methyl mercury. The mean concentrations of total Hg in
      broiled eels and broiled eel liver were 0.21 ppm and 0.10 ppm, respectively.
      Meanwhile, the mean concentrations of methyl mercury in broiled eels and broiled
      eel liver were 0.085 ppm and 0.039 ppm, respectively. The rate of methyl mercury
      to total Hg mainly ranged from 60 to 80% in broiled eels and from 35 to 65% in
      broiled eel liver. The total Hg concentrations of 2 samples of broiled eels and
      one sample of broiled eel liver exceeded the provisional regulation limit (0.4
      ppm) of total Hg in fish in Japan. In these samples, the rates of methyl mercury
      to total Hg were lower than 20%. The muscles and the skin of broiled eels were
      measured separately. The ratios of skin to muscle concentration of total Hg and
      methyl mercury were mainly in the range from 1/10 to 1/4. The mean intakes of
      total Hg from broiled eels and broiled eel liver per individual were 24.6 microg
      and 3.1 microg, respectively. The mean intakes of methyl mercury from broiled
      eels and broiled eel liver per individual were 10.4 microg and 1.2 microg,
      respectively.

PMID- 16440795
TI  - [Study of pesticide residues in agricultural products for the "Positive List"
      system].
AB  - During a 3-year monitoring survey (April 2002-March 2005) of pesticide residues
      in agricultural products, 592 samples (324 domestic; 268 imported) collected in
      Hyogo prefecture, Japan were analyzed. The number of pesticides tested increased
      from 232 in FY 2002 to 323 in FY 2004. The purpose of the study was to clarify
      the residue status by accumulating information about pesticides detected
      frequently, to allow effective and efficient regulation under the new "Positive
      List" legislation to be implemented in FY 2006. Overall, 47% of domestic and 61%
      of imported samples contained detectable residues and ca. 60% of positive samples
      contained multiple residues. The limit of quantitation was set at 0.01 microg/g
      and the limit of detection was 0.001-0.003 microg/ g. Most of the residues were
      present at low concentrations: 80% of the detections in samples excluding
      imported citrus fruits were < 0.05 microg/g. More than 5 different pesticides (>
      0.01 microg/g) were detected simultaneously in 13 samples. The sum of the ratios
      of residues to MRLs was calculated as one of the indexes to represent the risk of
      multiple residues, and they exceeded 100% in 3 imported frozen vegetables; baby
      kidney bean, spinach, Welsh onion. Samples in violation of the Food Sanitation
      Law were not found in our survey, but 1.9% of the samples might be in conflict
      with the new "Positive List" legislation.

PMID- 16440793
TI  - [Inter-laboratory validation studies of analytical method for determination of
      chloramphenicol in royal jelly].
AB  - Inter-laboratory validation studies were conducted in 6 laboratories to validate
      the analytical method for determination of chloramphenicol in royal jelly.
      Chloramphenicol spiked at the levels of 0.1 and 0.5 ppm was analyzed. Mean
      recoveries were 89 and 89%, reproducibility relative standard deviations (RSD(R))
      were 10.5 and 6.8%, HORRAT(R) values were 0.5 and 0.4. Samples containing
      residues at the levels of 0.25 and 0.80 ppm were analyzed. Mean recoveries were
      89 and 84%, RSD(R) were 9.8 and 12.3%, and HORRAT(R) values were 0.5 and 0.7. The
      determination limit was 0.05 ppm. These results show that this method has good
      performance.

PMID- 16440790
TI  - [Determination of 4-hexylresorcinol residues in prawns and crabs].
AB  - A method for the determination of 4-hexylresorcinol residues in prawn and crab
      meat by HPLC was developed. 4-Hexylresorcinol in prawn and crab meats was
      extracted with methanol using a homogenizer. The extract was diluted 4 times with
      water, and the diluted solution was passed through a C18 cartridge. The cartridge
      was washed with water and methanol-water (4 : 6), and then 4-hexylresorcinol was
      eluted with acetonitrile-0.1% phosphoric acid (55 : 45). The eluate was separated
      on a Capcell Pak C18 MG column with a mobile phase of acetonitrile-0.1%
      phosphoric acid (6 : 4) and 4-hexylresorcinol was determined with a UV detector
      (210 nm). Recoveries of 4-hexylresorcinol from commercial prawn and crab meats
      spiked at 1.0 and 10 microg/g were 82.4-92.2 and 88.9-91.8%, respectively. The
      determination limit of 4-hexylresorcinol was 1.0 microg/g in the samples.

PMID- 16440789
TI  - [Analysis of phenmedipham in agricultural products by HPLC].
AB  - An analytical method was developed for the determination of phenmedipham (PM) in
      agricultural products using reversed-phase high-performance liquid chromatography
      with UV detection. A sample was extracted with acetonitrile, and the acetonitrile
      layer was separated by salting-out. The acetonitrile phase was isolated and
      evaporated. The extract was dissolved in diethyl ether-hexane (1 : 1), and then
      cleaned up on a Florisil column. The column was washed with diethyl ether-hexane
      (1 : 1), and PM was eluted with acetone-hexane (3 : 7), and the eluate was
      evaporated. The residue was dissolved in acetone-hexane (2 : 8), and the sample
      solution was cleaned up on SAX/PSA cartridge. The SAX/PSA cartridge was washed
      with acetone-hexane (2 : 8), and PM was eluted with acetone-hexane (3 : 7). If
      required, the eluate of the Florisil column was cleaned up with SAX/PSA and ENVI
      Carb/ NH2 cartridges. The SAX/PSA cartridge was washed with acetone-hexane (2 :
      8), and connected to be ENVI-Carb/NH2 cartridge. The cartridges were washed with
      acetone-hexane (3 : 7), and then the SAX/PSA cartridge was removed. PM was eluted
      with acetonitrile-toluene (3 : 1) from the ENVI-Carb/NH2 cartridge. PM in the
      eluate was separated isocratically on an ODS column (4.6 mm i.d. x 150 mm, 5
      microm) using acetonitrile-water (6 : 4) as a mobile phase (flow-rate 1.0 mL/min,
      temp. 40 degrees C), with monitoring at 235 nm. The calibration curve was linear
      from 0.005 microg/mL to 10 microg/mL of PM. The recoveries of PM from eight kinds
      of agricultural products spiked at levels of 0.1 and 0.02 microg/g were 80.8
      98.7%. The determination limit was 0.01 microg/g.

PMID- 16440798
TI  - [Introduction of the "Positive List" system for agricultural chemicals in foods
      and development of analytical methods --recent amendment of regulation on
      pesticides by the Ministry of Health, Labour and Welfare, the Ministry of
      Agriculture, Forestry and Fisheries, and the Ministry of the Environment].

PMID- 16440797
TI  - [SRM in BSE infected animals and food safety].

PMID- 16440800
TI  - [Prognostic value of serum markers for liver fibrosis in transient abnormal
      myelopoiesis (TAM)].
AB  - Transient abnormal myelopoiesis (TAM) is usually a self-limiting
      myeloproliferative disorder observed in approximately 10% of newborn infants with
      Down syndrome. However, progressive liver fibrosis may occur in patients with TAM
      and is often lethal. We investigated the utility of the serum levels of
      hyaluronic acid (HA) and N-terminal peptide of III procollagen (P-III-P) as
      markers of liver fibrosis and indication for chemotherapy. We reviewed 4 cases of
      TAM retrospectively. HA levels were more than one hundred times as high as the
      upper limit of the normal range in 2 patients, one of whom died from
      gastrointestinal bleeding. His HA and P-III-P had increased up to 18,800 U/ml and
      26.2 ng/ml, respectively, just before he died. Another patient's serum HA and P
      III-P increased to 6,100 U/ml and 12.8 ng/ml, respectively, however his liver
      fibrosis resolved with low-dose cytosine arabinoside treatment after exchange
      transfusion during his clinical course. We suggest that serum HA is useful as a
      marker of liver fibrosis and a prognostic indicator for chemotherapy in patients
      with TAM. Early treatment including both exchange transfusion and chemotherapy
      should be considered for patients presenting with extremely high or an elevating
      tendency of their HA serum levels.

PMID- 16440802
TI  - [Pentostatin treatment for a patient with chronic type adult T-cell leukemia
      undergoing hemodialysis].
AB  - This is a preliminary feasibility study to assess the pharmacokinetics and
      efficacy of pentostatin in a patient undergoing dialysis. Pentostatin is a safe
      and well-tolerated medication, but a dose reduction is required for patients with
      renal insufficiency. We present a patient with chronic adult T-cell leukemia,
      whose white blood cell count exceeded 100 X 10(9)/l, and end-stage renal disease,
      receiving long-term thrice-weekly dialysis. The initial treatment with oral
      cyclophosphamide or with oral etoposide resulted in no response. After informed
      consent was obtained, pentostatin (1, 2, or 3mg/m2) was administered. 1 or 2
      hours after injection, the patient received hemodialysis over 4 hours to remove
      any of the drug remaining in his system. Plasma concentrations of pentostatin
      were calculated with the known pharmacokinetics parameters. The differential
      equations describing a 2-compartment open-infusion pharmacokinetic model were
      fitted to the measured concentration-time data. Tumor lysis syndrome occurred 4
      days after the course of the highest dose (3mg/m2), and the patient achieved
      complete remission. Anorexia, graded as 2 according to the NCI-CTC classification
      system, occurred and continued for four weeks. Pentostatin therapy consisting of
      the decreased dose (2mg/m2) was then administered every other week and provided a
      transient partial response with mild anorexia. Consequently, pentostatin can be
      considered as one of the chemotherapeutic regimens available for a patient
      undergoing dialysis.

PMID- 16440803
TI  - [Successful rituximab treatment in a patient with refractory hairy cell leukemia
      Japanese variant and suffering from acute respiratory distress].
AB  - A 69-year-old man was referred to our hospital because of thrombocytopenia and
      was diagnosed as having hairy cell leukemia-Japanese variant (HCL-Jv) in December
      2000. In June 2002, he was treated with pentostatin for progression of
      thrombocytopenia, but his response was incomplete. In addition, the number of
      hairy cells (HCs) in his peripheral blood (PB) began gradually to increase. He
      received treatment with interferon-alpha and cladribine, but he failed to respond
      completely to these treatments. The HCs in his PB decreased after splenic
      irradiation in July, 2004. However, he was admitted with acute respiratory
      distress in November. His white blood cell count was 123.1 X 10(9)/L with 91%
      HCs. Radiography and computed tomography of his chest revealed ground-glass
      opacity in both lungs. A bone marrow (BM) aspirate indicated increased
      cellularity with an 84% HC infiltration level. Based on these findings, we
      diagnosed pulmonary infiltration by HCs. Rituximab was administered weekly at a
      dose of 375 mg/m2, and he also received low-dose melphalan in a supportive role.
      After 8 courses of rituximab therapy, the HCs disappeared in his PB and BM, and
      his pulmonary infiltrates subsided. These results suggest that rituximab may be a
      very effective treatment for refractory HCL-Jv.

PMID- 16440801
TI  - [Successful treatment with cladribine for hypoplastic hairy cell leukemia after
      long-term neutropenia].
AB  - A 34-year-old woman was admitted to the hospital because of swelling of her right
      knee, and the result of the laboratory tests indicated anemia and leukocytopenia.
      A bone marrow examination showed dissemination of small to medium-sized abnormal
      lymphocytes with abundant and pale blue cytoplasm and a circumferential "hairy"
      projection in the hypocellular bone marrow. These cells were positive for
      tartrate-resistant acid phosphatase (TRAP) and for CD 19, CD 20, CD 25, CD 103
      and SmIg kappa. The patient was diagnosed as having hypoplastic hairy cell
      leukemia and received cladribine (2-CdA) for seven days via continuous
      intravenous injection. The minimum white blood cell count was 300/microl at seven
      days after starting the therapy (day 7) and the neutrophil count recovered to
      more than 1500/microl on day 118. The patient achieved complete remission on day
      140 without any episodes of severe infection and has remained in complete
      remission for more than one year. The treatment of hypocellular HCL with 2-CdA
      might be useful.

PMID- 16440799
TI  - [Methods for reducing the levels of acrylamide monomer in processed foods].

PMID- 16440804
TI  - [Acute lymphoblastic leukemia with t(4;11)(q21;q23) after iodine-131 treatment
      for thyroid cancer].
AB  - A 49-year-old Japanese woman was diagnosed on March 1996 as having thyroid cancer
      with lung metastasis. Following a total thyroidectomy, she was treated with a
      total dose of 350 mCi iodine-131 (131I) for metastatic thyroid cancer. Four years
      later she returned to our hospital under the chief complaint of subcutaneous
      bleeding. Hematological examinations revealed marked leukocytosis associated with
      anemia and thrombocytopenia. A bone marrow aspiration showed a hypercellular
      marrow consisting of 90% blasts negatively stained by myeloperoxidase.
      Immunophenotyping of the blasts indicated they were CD19, 34, HLA-DR positive but
      CD3, 10, 13 negative. She was given the diagnosis of pro-B acute lymphoblastic
      leukemia (pro-B ALL). Cytogenetic analysis showed a chromosomal aberration t(4;
      11)(q21; q23) and MLL-AF4 chimeric gene mRNA was detected by RT-PCR analysis. She
      had never been exposed to any kind of chemoradiotherapy other than 131I therapy
      and her leukemia showed a t(4; 11) chromosomal aberration and no expression of
      CD10 on the blasts, which are the characteristics frequently found in therapy
      related pro-B ALL patients, suggesting a relationship between the development of
      pro-B ALL with t(4; 11) and 131I therapy. Although leukemia has been recognized
      as a late uncommon complication after 131I therapy for thyroid cancer, to the
      best of our knowledge this is the first patient who developed ALL with t(4 ;11)
      after 131I therapy among patients with thyroid cancer.

PMID- 16440805
TI  - [Successful treatment with interferon-alpha in a case of acute myeloid leukemia
      with del (20q) following polycythemia vera].
AB  - Polycythemia vera (PV) is a hematopoietic stem cell clonal disorder, 5 to
      approximately 10% of which will evolve into acute leukemia. The pathophysiology
      of leukemic transformation and the best therapy for the leukemic phase of PV is
      still unknown. A 73-year-old woman was given a diagnosis of PV 17 years
      previously. However, laboratory data revealed myeloblasts in the peripheral blood
      with macrocytic anemia and thrombocytosis in March 2003. Bone marrow examination
      in October 2003 revealed 32.8% myeloblasts with trilineage dysplasia. Chromosomal
      analysis of the bone marrow cells revealed that 18/22 of mitotic cells had
      del(20q) and 3/22 of had t(2; 12). The leukemic phase of PV was diagnosed. She
      achieved not only a hematologic remission, but also cytogenetic remission after
      interferon (IFN)-alpha treatment. As far as we know, this is the first report of
      the introduction of IFN-alpha in the treatement of the leukemic phase of PV.
      Further monitoring of this patient will provide valuable information concerning
      the pathophysiology of leukemic transformation and the development of effective
      therapy for the leukemic phase of PV.

PMID- 16440807
TI  - [Therapy-related acute promyelocytic leukemia with a t(9;22)(q34;q11) and
      t(15;17)(q22;q11 to approximately 12) subclone].
AB  - The translocation (15;17) is a typical marker of acute promyelocytic leukemia,
      whereas t(9;22) is predominantly associated with chronic myelogenous leukemia,
      and seldom with acute myelogenous leukemia. Furthermore, the association between
      t(15;17) and t(9;22) in the same cell is extremely rare. We present a case of
      therapy-related acute promyelocytic leukemia (t-APL) with a subclone accompanied
      by karyotype 46, XX, t(9; 22)(q34;q11), t(15 ;17)(q22;11 to approximately 12) at
      onset. A 75-year-old woman was diagnosed as having non-Hodgkin lymphoma of the
      thyroid gland in July 1997. She was treated with a CHOP-like regimen, but
      complete remission (CR) was not achieved. She then underwent surgical resection
      of her thyroid gland, and was treated with etoposide (total dose 16775 mg) from
      February 1998 to May 2000. In June 2000, having developed t-APL, she was referred
      to our department. The patient attained CR following treatment with chemotherapy
      containing all-trans retinoic acid. Ten months later she relapsed, but lost the
      t(9;22), while maintaining the t(15;17).

PMID- 16440806
TI  - [Chronic GVHD with polymyositis after non-myeloablative stem cell
      transplantation].
AB  - A 57-year-old man underwent an autologous hematopoietic stem cell transplant for
      mantle cell lymphoma in August 1999. Anemia and thrombocytopenia appeared in
      November 2001. He was diagnosed with further hematological examination as having
      acute myeloid leukemia with multilineage dysplasia following secondary
      myelodysplastic syndrome. He received the allogeneic hematopoietic stem cell
      transplant from his HLA DRB1 locus mismatched brother in May 2002. The
      nonmyeloablative preparative regimen consisted of fludarabine 30mg/m2 for 6 days
      and busulfan 4mg/kg for 2 days. Eosinophilia, decrease of lacrimal fluid and
      liver dysfunction appeared on Day 104. We diagnosed this as chronic GVHD and
      treated the patient with prednisolone 10 mg/day. Thereafter, his chronic GVHD
      gradually improved. He had fever and myalgia in the extremities and lumbar region
      with elevated serum CPK and aldolase in January 2003. Histological examination
      led to a diagnosis of polymyositis simultaneously with chronic GVHD. Prednisolone
      50 mg/day as an initial dose was started for the polymyositis following which the
      prednisolone dose was gradually tapered off. The polymyositis improved promptly
      after the administration of prednisolone and remains in remission with a current
      maintenance program of prednisolone 5 mg/day.

PMID- 16440812
TI  - [Aberrant promoter hypermethylation of tazarotine-induced gene 1 (TIG1) in head
      and neck cancer].
AB  - We tested the methylation status of tazarotine induced gene 1 (TI(G1) in head and
      neck cancer cell lines and primary tumors by the methylation-specific polymerase
      chain reaction (MSP). MSP showed that the TIG1 promoter was methylated in all
      cell lines. We then used MSP to check the methylation status of TIG1 in primary
      head and neck cancer (n = 50). MSP showed TIG1 methylation in 31 (62%) head and
      neck cancers and no methylation in any normal samples. To confirm MSP results, we
      directly sequenced dense CpG regions. We found that promoter regions contained
      methylated cytosines. We thus observed a cancer-specific pattern of TIG1
      methylation in primary head and neck cancer. Our results support the notion that
      promoter methylation is an important mechanism of TIG1 gene inactivation and
      occurs frequently in head and neck cancer. TIG1 methylation represents a new
      molecular marker for targeting diagnostic and therapeutic approaches in these
      cancers.

PMID- 16440808
TI  - [Oral administration of arsenic trioxide induced molecular remission in relapsed
      acute promyelocytic leukemia].
AB  - I report on a 21-year-old man with acute promyelocytic leukemia (APL) which
      relapsed after a therapeutic regimen consisting of tretinoin, daunorubicin,
      enocitabine, mitoxantrone, and cytarabine. The patient also had severe mental
      retardation caused by a congenital central nervous system malformation.
      Administration of arsenic trioxide (As2O3) is indicated for patients with APL,
      however, daily intravenous infusion of As2O3 presented problems because of the
      patient's violent resistance to venous access. Accordingly, 10mg of an oral
      solution of As2O3 was given once daily for 70 days. No adverse events were
      observed with the exception of transient hyperleukocytosis and fever. The patient
      achieved molecular remission 103 days after the start of oral As2O3, and remains
      in remission after an additional 2 courses of oral As2O3 as consolidation
      chemotherapy. Oral As2O3 may be useful in the treatment of relapsed APL as an
      alternative to intravenous As2O3.

PMID- 16440809
TI  - [Generalized erythema triggered by a rapid decrease of basophils in chronic
      myeloid leukemia treated with imatinib].
AB  - A 57-year-old woman with chronic myeloid leukemia showing severe basophilia (WBC
      17.1 X 10(9)/L, basophils 23%) was treated with 400mg imatinib in June 2003. A
      high basophil count (WBC 10.6 X 10(9)/L, basophils 31%) was still observed after
      1 week of therapy. After 9 days of therapy, she developed generalized pruritic
      skin erythema, chills and high fever. After terminating imatinib treatment,
      prednisolone therapy was initiated. The rash quickly disappeared. Four days after
      withdrawal of imatinib, leukocyte count was 13.0 X 10(9)/L with 3% of basophils,
      suggesting the possibility that rapid decrease in basophils following imatinib
      therapy may induce severe cutaneous reactions.

PMID- 16440810
TI  - [Elderly patient with varicella-zoster virus-associated hemophagocytic syndrome
      refractory to steroid therapy].
AB  - We experienced a case of virus-associated hemophagocytic syndrome (VAHS) after
      varicella-zoster virus (VZV) infection. The patient, a 101-year-old man,
      presented with anemia, thrombocytopenia and jaundice two weeks after successful
      antiviral treatment for the VZV. Histiocytes were detected in the bone marrow
      examination (2.2%); however, hepatomegaly and triglycemia remained unobserved
      throughout the course. Reactivation of VZV was detected serologically. The
      patient died after five weeks because of persistent cytopenia and liver failure
      refractory to steroid treatment. An autopsy revealed hemophagocytosis in the bone
      marrow, lung, spleen and liver.

PMID- 16440811
TI  - [Audiological effect of bone-anchored hearing aid].
AB  - The bone-anchored hearing aid (BAHA) has proved to be a valuable alternative to
      conventional air and bone conduction hearing aids for patients suffering from
      chronic otitis media or bilateral aural atresia. The BAHA gave better sound
      quality and greater comfort than conventional hearing aids (HAs), but only 1
      study has been done in Japan. We implanted BAHAs in 6 hard-of-hearing patients in
      the last 2 years. One patient suffered skin problems around the abutment and used
      the BAHA only briefly. Free-field audiometry, the speech discrimination test
      (SDT), and the speech recognition test (SRT) were conducted in all subjects. They
      were evaluated either with the HA or BAHA. The SDT and SRT showed better hearing
      results in quiet for the BAHA than the conventional HA, but there was a minimum
      difference in SDT and SRT in noise. Subjects assessed the HA and BAHA using
      questionnaires. Subjects reported that the BAHA offers a number of important
      advantages, including greater cosmetic acceptability, improved speech
      intelligibility, and better sound quality.

PMID- 16440813
TI  - [Evaluation of the quality of life in sudden deafness patients by HHIA (hearing
      Hatidicap Inventory) and questionnaire].
AB  - After treatments, several patients with sudden deafness (SD) continued to have
      symptoms, including hearing loss, tinnitus and dizziness. These unresolved
      symptoms and their effect on the quality of life (QOL) in SD patients have not
      been studied. We evaluated QOL using the Hearing handicap inventory (HHIA) and an
      original questionnaire in SD patients who had been treated more than 6 months
      prior to the study. Compared to results in bilateral sensorineural hearing were
      significantly lower in SD patients (p<0.01). In bil SNHL, this score peaked two
      to 10 years after onset of disease and decreased thereafter. The score peaked
      more than 10 years after onset of disease in patients with SD. While hearing and
      test scores were correlated in bil-SNHL, this was not observed in SD. About half
      of patients were embarrassed by hearing loss and tinnitus after treatment. Among
      patients who scored more than 44 points on HHIA, all reported hearing loss and
      tinnitus. When asked about subjective changes in hearing after treatment, 27%
      believed their hearing had improved, 60% believed there was no change, and 13%
      believed their hearing had deteriorated. Cases believing deterioration in hearing
      also had high scores on HHIA. Sequelae of SD may worsen QOL, driving embarrassed
      patients to visit other medical facilities in to improve their QOL. Even though
      hearing may not improve after initial treatment in ears affected by SD, informed
      consent about the clinical course and audiological follow-up should be done.

PMID- 16440814
TI  - [The advantage of our original straight cannula for tracheostoma].
AB  - Patients with head and neck cancers often require use of a tracheal cannula due
      to stenosis of the permanent tracheostoma following total laryngectomy. However,
      a cannula that is designed for a multi-purpose tracheotomy frequently presents a
      problem, when placed in a permanent tracheostoma. To resolve this difficulty, we
      developed a straight cannula that fits most permanent tracheostomas. We achieved
      a straight design by removing the curvature of a cuffed tracheostomy single
      cannula (size 12: Koken Co., Ltd.). To facilitate installation by the patient
      without assistance, silicone was used because it is softer than similar
      conventional products. By making the cannula diameter slightly larger,
      immobilization with a strap is lomger needed. Our cannula was used in 14 patients
      following surgery for the laryngeal, hypopharyngel, esophageal carcinomas. The
      cannula fit well and reduced the respiratory discomfort in all patients.

PMID- 16440817
TI  - Three successful pregnancies with in vitro fertilization embryo transfer over an
      eight year time span despite elevated basal serum follicle stimulating hormone
      levels. Case report.
AB  - PURPOSE: To demonstrate that elevated basal follicle stimulating hormone (FSH)
      does not necessarily signify poor quality eggs. METHODS: In vitro fertilization
      embryo transfer (IVF-ET) performed because of unexplained infertility and male
      factor related to low hypo-osmotic swelling test. RESULTS: Three live pregnancies
      following lowering of elevated serum FSH with ethinyl estradiol followed by
      gonadotropin therapy. The patient had seven attempted oocyte retrievals and five
      led to ET. Despite markedly elevated basal serum FSH levels she achieved a
      delivered pregnancy rate of 42.8% per retrieval, 60% per transfer and an
      implantation rate of 27.2%/embryo transfer. CONCLUSIONS: This study clearly shows
      that high serum FSH in a woman of younger reproductive age does not mean egg
      quality is poor. The case also shows that since ovulation induction was still
      possible eight years later that the paucity of eggs in younger women is more
      likely related to a previous catastrophic event that markedly diminished egg
      reserve but that egg atresia proceeds at the normal rate thereafter.

PMID- 16440815
TI  - [A case of fibromyalgia treated with medical and autogenic training].
AB  - Fibromyalgia, which is relatively rare, may include symptoms of dizziness,
      vertigo and tinnitus. Subject was 38 years old woman reporting vertigo and whole
      body pain. Cochleovestibular function was normal. Pain was gradually intensified
      during her outpatient clinic and she was admitted. Treatments including
      intramusclular injection of botulinus toxin and intravenous injection of steroid
      were applied. Psychological counseling and autogenic training were effective in
      relieving her pain and vertigo. During her admission, several spells of vertigo
      occurred but no nystagmus was found. The abnormality in proprioception and neural
      disintegration may be related to vertigo. Treatment should start as early as
      possible together with psychological therapy.

PMID- 16440818
TI  - Development of mammalian embryos exposed to mixed-size nanoparticles.
AB  - Inhaled or ingested ultrafine nanoparticles and their effects on early pregnancy
      remain polemic. The objectives of the study were: (a) to determine the
      embryotoxic effects of nanoparticles at the 2-cell stage and (b) to localize the
      internalized nanoparticles in the blastocyst. Thawed mouse 2-cell embryos (no. =
      128) were exposed to either mixed-size polystyrene-based nanoparticles (11
      million/ml) or control G1.3 medium and assessed after 72 hours. Additionally,
      blastocysts (no. = 146) were exposed to nanoparticles and analyzed. The results
      showed that the nanoparticles did not inhibit 2-cell embryo development to the
      blastocyst stage (89.4 vs 96.8%; treated vs control). There were no differences
      in hatching (34.8 vs 43.5%), implantation (13.6 vs 24.2%) and degeneration (10.6
      vs 3.2%). Delayed exposure to nanoparticles showed similar percent hatching (40.7
      vs 47.3%) and implantation (17.6 vs 20.0%). Although nanoparticles were
      internalized, embryo development was not inhibited suggesting a lack of
      embryotoxicity. During hatching, the larger nanoparticles adhered to the
      extruding blastocyst, preferentially on trophoblasts, but interference was
      insignificant. Exposure to polystyrene-based nanoparticles at the concentration
      tested are not associated with embryonic loss.

PMID- 16440816
TI  - A novel method to evaluate pregnancy rates following in vitro fertilization to
      enable a better understanding of the true efficacy of the procedure.
AB  - PURPOSE: To propose a new method of evaluating in vitro fertilization (IVF)
      embryo transfer (ET) outcome so that statistics are not biased against IVF
      centers that have strong cryopreservation programs. METHODS: A retrospective
      review was made of all patients undergoing IVF-ET in a four and a half year time
      period having at least two embryos transferred. There were no other exclusions.
      All types of problems and controlled ovarian hyperstimulation protocols were
      used. Data were analyzed according to four age groups: < or =35, 36-39, 40-42, >
      or =43. Pregnancy rates were calculated according to a given oocyte harvest where
      a pregnancy was counted if the woman conceived on the fresh transfer or any
      succeeding frozen ET from embryos obtained from oocytes retrieved on that
      harvest. Also pregnancy rates per transfer and retrieval were evaluated. RESULTS:
      For women < or =35 to age 39 the new category of clinical pregnancy rate per
      oocyte harvest was significantly higher than the pregnancy rate per transfer. The
      pregnancy rate per transfer was significantly higher than the pregnancy rate per
      retrieval in women up to age 42. CONCLUSIONS: We propose that calculating
      pregnancy rate per harvest is the best method to evaluate the true efficacy of
      IVF-ET especially from programs with a strong emphasis on cryopreservation.

PMID- 16440819
TI  - Aided visual inspection with acetic acid (VIA) and HPV detection as optional
      screening tools for cervical cancer and its precursor lesions.
AB  - PURPOSE OF INVESTIGATION: To assess the contribution of visual inspection with
      acetic acid (VIA) and Hybrid Capture II (HCII) as adjunct methods to the Pap test
      in detecting cervical neoplasia. SUBJECTS AND METHODS: This was a cross-sectional
      study with 809 women who consecutively attended gynecological consultations at
      Campinas University, Brazil, from January 2002 to July 2003. Pap test, HCII, VIA,
      and colposcopy were offered to all patients. Performance of tests (alone or in
      combination) in detecting histologically confirmed lesions was evaluated.
      RESULTS: Of the 40 patients with CIN, 69% had CIN1, 26% CIN2 or CIN3 and one
      patient had invasive carcinoma. VIA had the best performance in detecting CIN,
      yielding 72% sensitivity and 91% specificity. Considering only CIN2 or worse as
      significant lesions, HCII had the best sensitivity (73%), while the Pap test was
      the most specific (93%). Combining the three exams, 92% of the CIN1 or worse were
      detected. When CIN1 was excluded from the analysis, Pap smear plus HCII delivered
      82% sensitivity and 79% specificity. However, this combination yielded a very low
      (5%) PPV. CONCLUSION: VIA and HCII contributed to the screening of cervical
      neoplasia in a group of Brazilian women, but the cost-effectiveness of conjoint
      screening modalities is still debatable.

PMID- 16440820
TI  - Effects of laparoscopic tubal ligation on ovarian blood flow and steroidogenesis.
AB  - Changes in serum ovarian hormone and gonadotrophine levels and ovarian artery
      blood flow rate by Doppler ultrasonography following laparoscopic tubal
      sterilization were evaluated. Forty-seven cases of laparoscopic tubal
      sterilization by electrocoagulation were included in the study. Forty-two women
      who used nonhormonal contraceptive methods were randomized as a control group.
      Serum concentrations of estradiol, FSH, LH, progesterone and bilateral ovarian
      artery pulsatility indexes were measured at baseline and at three, six and 12
      months. In the study group, the mean value of midluteal progesterone was
      significantly decreased three months postoperatively 3. and bilateral ovarian
      artery pulsatility indexes were increased three and six months postoperatively,
      compared to their preoperative values. However, there was no statistical
      difference between bilateral ovarian PI values calculated preoperatively and at
      12 months. Laparoscopic tubal ligation by electrocoagulation may temporarily
      cause reduced bilateral ovarian artery flow and corpus luteum dysfunction proven
      by low mid-luteal progesterone levels.

PMID- 16440821
TI  - Hysterectomy: benefits of clinical performance indicators in the evaluation of
      healthcare facilities.
AB  - PURPOSE: The aim of our study was to verify, by applying clinical performance
      indicators, the quality of healthcare given to hysterectomy patients and the
      benefits on their adoption in healthcare facilities. METHODS: The different
      surgical approaches and indications for surgery were evaluated in 534 patients
      analysing postoperative short-term complications and triggered clinical
      performance indicators (CPIs). RESULTS: Surgery was performed by the abdominal
      (80.9%) and vaginal route (19.1%). Postoperative complication rate was 13.5% and
      CPIs were triggered 108 times overall: 42 in benign conditions (10.3%) and 30 in
      malignancy (23.4%) (p = 0.001). In patients operated on for benign conditions the
      different approaches, abdominal or vaginal, showed differences in postoperative
      period (p = 0.4). In 10.9% of malignant and in 2.9% of benign conditions hospital
      stay was triggered (p = 0.001). Vaginal surgery showed a shorter average stay
      than laparotomy (p = 0.001). CONCLUSION: The use of CPIs may determine a
      refinement of clinical performance with positive effects on health, patient
      satisfaction, postoperative morbidity hospitalisation and healthcare cost
      savings.

PMID- 16440823
TI  - A ten-year gestational diabetes mellitus cohort at a university clinic of the mid
      Anatolian region of Turkey.
AB  - OBJECTIVE: The study attempts to analyze a 10-year retrospective cohort of
      gestational diabetes mellitus (GDM) cases, elucidating the maternal complications
      and perinatal morbidity and mortality. STUDY DESIGN: The study participants were
      110 diabetic singleton pregnancies receiving obstetric care at the Department of
      Obstetrics and Gynecology, Osmangazi University School of Medicine in Eskisehir,
      Turkey from January 1995 to December 2004. In 70 of the GDM cases, mean age,
      diagnostic criteria used to define GDM, gestational age at delivery, presence of
      additional risk factors, method of clinical management, mode of delivery, fetal
      birthweights and newborn characteristics were assessed. RESULTS: The prevalence
      of GDM in the past ten-year period was 3.1% (110/3548). Mean age of enrolled GDM
      cases was 32.6 +/- 5.3 years. With regard to diagnostic criteria of GDM, 24
      (37.1%) cases were diagnosed based on a 100 g, three-hour oral glucose tolerance
      test (OGTT), while 18 (25.7%) cases were referred to our unit without any
      information on the specific criteria of GDM diagnoses. In less than a third of
      the cases (25.7%), a one-hour 50 g glucose challenge test (GCT) resulted > or
      =185 mg/dl completing the diagnoses. More than half of the cases (57.1%) revealed
      controlled glucose homeostasis on diet, while 30 (42.9%) pregnant women needed
      insulin therapy to control blood glucose levels to within normal physiologic
      limits. Fetal macrosomia was present in 18 (25.7%) pregnancies. Meanwhile, most
      of the fetuses (62.9%) were within the normal growth percentiles throughout the
      pregnancy. There was no difference detected in body mass index (BMI) of women
      undergoing cesarean section and spontaneous vaginal births (25.1 +/- 1.2 vs 26.2
      +/- 2.3 kg/m2, respectively, p = 0.45). Vacuum extraction and forceps
      applications were indicated in 10% of all GDM groups. Fetuses born to women
      having cesarean section were heavier at birth compared to those of women having
      vaginal births (3940 +/- 320 g vs 430 +/- 117 g, p = 0.08) Most frequent neonatal
      morbidity was hyperbilirubinemia in 25 (35.7%) newborns. Interestingly, of those
      women with GDM, only ten (14.3%) cases consented to follow-up evaluation of
      glucose intolerance between six and eight weeks postpartum. CONCLUSIONS: Proposed
      risks from abnormal glucose intolerance in pregnancy are multiple. Early
      diagnosis, patient education, proper follow-up and postpartum testing in women
      with GDM will certainly decrease poor perinatal outcomes, enabling also a
      secondary prevention of type 2 diabetes in the long term.

PMID- 16440822
TI  - Evaluation and importance of asymptomatic bacteriuria in pregnancy.
AB  - OBJECTIVES: This study was undertaken to determine the incidence of asymptomatic
      bacteriuria (ASB) during pregnancy and its prevalance in the three trimesters.
      SUBJECTS AND METHODS: One hundred and ten pregnant women in their first trimester
      attending the antenatal outpatient clinic with no urinary tract complaints were
      included in the study. After perineal cleaning, urine samples were obtained from
      all patients for culture and microscopic evaluation. Approximately 1 ml urine was
      sampled using the mid-stream catch technique. Patients with bacterial counts over
      100,000 with the mid-stream catch technique were considered to have asymptomatic
      bacteriuria. Patients fulfilling the criteria for bacteriuria were treated with
      either penicillin or cephalosporine for one week, depending on the in-vitro
      sensitivity test results. RESULTS: ASB rate in the study group was 8.1%. E. coli
      was isolated as the pathogenic organism in 77.77% of the cases with ASB. ASB was
      found to be more frequent in patients over age 25 and the average age of pregnant
      women with ASB was 29.89 +/- 5.80 (p < 0.05). Average duration of gestation in
      the group with ASB was 28.11 +/- 2.26 weeks. ASB rate in the group age 35 and
      over was 22.22% (p < 0.05). ASB was diagnosed in nine patients; one of these
      patients was in the first trimester, two were in the second trimester, and six in
      the third trimester. Clustering in the third trimester was found to be
      statistically significant (p < 0.05). CONCLUSION: ASB distribution in the first,
      second, and third trimesters was 0.9%, 1.83%, and 5.6%, respectively. There was a
      significant relationship between advanced maternal age and incidence of ASB.
      Women with no bacteriuria in their initial examination in the first trimester
      developed bacteriuria in the later trimesters. We, therefore, suggest that it
      would be prudent to screen pregnant women for bacteriuria in the second and third
      trimesters.

PMID- 16440824
TI  - Uterine torsion with maternal death: our experience and literature review.
AB  - Torsion of the gravid uterus around its cervical junction is a rare event
      especially in humans. In 1992, a literature review by Jensen, mentioned by
      Carbonne, showed 212 cases with different etiologies. Uterine torsion is more
      frequently dextrorotatory (2/3 of cases). The diagnosis is difficult and
      generally done during cesarean section because it is frequently not symptomatic.
      Uterine torsion signs, when present, are not specifics. Pain, nausea and vomiting
      may present without any sign of shock, as in our patient. Sometimes
      ultrasonography can lead to a correct diagnosis, showing a modification of the
      placenta site during pregnancy, or an abnormal positioning of the ovarian vessels
      which pass in front of the lower uterine segment. Some authors report
      cardiotocographic abnormalities probably due to the reduction of blood flow
      caused by the torsion. Quickness of surgical treatment is fundamental for the
      reduction of fetal mortality which is very frequent in a large number of cases,
      while maternal mortality is not so frequent but possible. A diligent anamnesis
      and ultrasonographic examination are surely useful to single out the rare cases
      of uterine torsion in pregnancy.

PMID- 16440825
TI  - A novel highly effective treatment of interstitial cystitis causing chronic
      pelvic pain of bladder origin: case reports.
AB  - PURPOSE: To determine if a very effective therapy for idiopathic orthostatic
      cyclic edema--dextroamphetamine sulfate--would alleviate symptoms of chonic
      pelvic pain of bladder origin/interstitial cystitis. METHODS: Two women with
      interstitial cystitis that had been refractory to various therapies were treated
      with dextroamphetamine sulfate (20 mg/day) without any other treatment. The
      diagnosis of idiopathic edema was made by abnormal water load test and
      interstitial cystitis diagnosed by elevated scores on the pelvic pain and urgency
      and frequency symptom scale. RESULTS: Both patients quickly improved their
      bladder symptoms and all pain and urgency was gone within a week. The
      interstitial cystitis remained in remission as long as the women stayed on their
      medication. One woman proved Koch's postulates by stopping the medication because
      of forgetting it and symptoms resumed quickly only to disappear again upon
      resuming therapy. CONCLUSIONS: Dextroamphetamine sulfate can be a very effective
      therapy for recalcitrant cases of interstitial cystitis. Prospective placebo
      controlled studies are needed to determine what percentage of patients with this
      debilitating condition have concomitant idiopathic edema as determined by
      abnormal water load test and how well a larger series will respond to this novel
      therapy.

PMID- 16440826
TI  - Consumptive coagulopathy that developed in a pregnant woman with degenerated
      uterine leiomyoma: case report.
AB  - A case of consumptive coagulopathy in a 30-year-old pregnant woman with
      degenerated uterine leiomyoma is described. She developed lower abdominal pain at
      21 weeks of gestation. Laboratory profiles revealed coagulation abnormalities.
      Magnetic resonance imaging diagnosed degenerated uterine leiomyoma. At 34 weeks,
      she underwent cesarean section and myomectomy. Pathological examination showed
      the presence of organized thrombi in the vessels of leiomyoma. The consumption of
      platelets and coagulation factors in degenerated uterine leiomyoma may result in
      consumptive coagulopathy.

PMID- 16440828
TI  - Diagnosis and treatment of early cervical pregnancy: a case report and literature
      review.
AB  - A case of an early cervical pregnancy diagnosed by transvaginal Doppler
      ultrasonography and successfully treated by systemic and local injection of
      methotrexate to avoid complications of the surgical procedures in use and to
      preserve future fertility is presented. This procedure may become a useful
      alternative to more radical or complex surgical approaches.

PMID- 16440827
TI  - Pregnancy in a woman after eight reconstructive urological operations due to
      bladder extrophy: case report.
AB  - The progress of reconstructive surgical treatment of congenital malformations is
      associated with an increasing number of patients requiring special care in
      pregnancy. Although there have been some communications concerning the management
      of pregnancy after one or two reconstructions of bladder extrophy, a case with a
      successful course of pregnancy after eight urological operations of this disorder
      is presented.

PMID- 16440830
TI  - Hodgkin's disease during pregnancy: a case report and review of the literature.
AB  - The simultaneous presence of cancer and pregnancy is rare but occurs, creating
      extreme scenarios in clinical practice. Hodgkin's disease (HD), affects primarily
      young adults and therefore obstetricians may confront young women with this type
      of lymphoma during pregnancy. We report a case of a 27-year-old woman with HD who
      presented during the 28th week of gestation. After counseling the couple decided
      to continue with the pregnancy. The patient received conservative treatment with
      regression of the symptoms and rapid improvement of her general condition. At 36
      weeks of gestation a healthy infant was born and the patient underwent
      chemotherapy after delivery with complete resolution of the disease.

PMID- 16440829
TI  - A pregnant woman with anti-Gregory antigen: case report.
AB  - Negative Gregory antigen (Gy(a-)) remains an extremely uncommon blood phenotype.
      We describe a 32-year-old pregnant woman with (Gy(a-)) and anti-Gregory antigen
      (anti-Gy(a)). There was no evidence of consanguineous mating in her family. Blood
      typing study revealed that only her father was Gy(a-) among the family. Anti
      Gy(a) had a titer of 16 before pregnancy, but increased to 1024 at 33 weeks of
      gestation with a titer of 512 at 34 weeks. Her own blood stores were collected
      starting at 14 weeks, amounting to 1800 g totally. She underwent an emergency
      cesarean section at 35 weeks due to a non-reassuring fetal status. Blood loss was
      approximately 1090 g. Cord blood type was found to be Gy(a-). The indirect Coombs
      test of cord blood was positive, while the direct Coombs test was negative. No
      neonatal hemorrhagic disease developed. The storage of a sufficient amount of
      crossmatch-compatible Gy(a-) blood during pregnancy is important in case of
      possible need of blood transfusion at delivery for women with anti-Gy(a).

PMID- 16440831
TI  - 46 XX male syndrome: a case report.
AB  - INTRODUCTION: 46 XX male syndrome (de la Chapelle syndrome) is a rarely seen
      genetic disorder causing male infertility. It is generally a result of unequal
      crossing over between X and Y chromosomes. CASE REPORT: A 26-year-old infertile
      male was referred to the Urology Department. He had normal external male genital
      phenotype and secondary sex characters. No gynecomastia was noted. At physical
      examination soft and atrophic testes were palpated. Laboratory analysis and
      testis biopsies indicated nonobstructive azospermia. Chromosomal analysis showed
      46 XX karyotype. CONCLUSION: In the literature, there are various phenotypic
      properties of 46 XX male patients. Thus, translocation of the sex determining
      region (SRY) the gene probably cannot be the only reason for XX male syndrome.
      There might be some other abnormalities leading to de la Chapelle syndrome.

PMID- 16440832
TI  - Squamous cell carcinomas of the ovary: report of four cases and literature
      review.
AB  - Two cases of squamous cell carcinoma developing in mature cystic teratoma and two
      cases with a malignant change involving an ovarian epidermal cyst diagnosed in
      our institution over a 15-year-period are reported. This is a reminder that such
      changes may occur and issues regarding the problem of the differential diagnosis
      and management of these rare complications are discussed.

PMID- 16440833
TI  - An alternative approach to evaluation of poolability for stability studies.
AB  - The current method for pooling the data from different batches or factors,
      suggested by ICH Q1E guidance, is to use analysis of covariance (ANCOVA) for test
      interaction between slopes and intercepts and factors. Failure to reject the null
      hypothesis of equality of slopes and equality of intercepts, however, does not
      prove that slopes and intercepts from different levels of factors are the same,
      and the data can be pooled for estimation of shelf life. In addition, the ANCOVA
      approach uses indirect parameters of intercepts and slopes in the regression
      model for assessment of poolability. The hypothesis for poolability is then
      formulated on the basis of the concept of equivalence for the means among the
      distributions of the quantitative attributes at a particular time point. Methods
      based on the intersection-union procedure are proposed to test the hypothesis of
      equivalence. A large simulation study was conducted to empirically investigate
      the size and power of the proposed method for the bracketing and matrixing
      designs given in the ICH Q1D guidance. Simulation results show that the proposed
      method can adequately control the size and provides sufficient power when the
      number of factors considered is fewer than three. A numerical example using the
      published data illustrates the proposed method.

PMID- 16440834
TI  - A note on ethnic sensitivity studies.
AB  - In this article, we propose a similarity criterion for ethnic sensitivity studies
      in pharmacokinetic variables. We present how this criterion can be used in the
      context of different dose-exposure models and how sample size and power
      calculations can be done. Examples for the planning and analysis of ethnic
      sensitivity studies are provided.

PMID- 16440835
TI  - On the treatment effect in clinical trials with dropout.
AB  - Patient's dropout often occurs in clinical trials with multiple scheduled visits,
      which results in a great challenge in the analysis of incomplete data. As the
      first step, one has to define a relevant treatment effect parameter, which is not
      straightforward in the presence of dropout. We discuss and compare two different
      treatment effect parameters that are adopted in most analyses of clinical data:
      the study-end treatment effect and the last-observed treatment effect. Some
      related issues, such as the estimability of causal parameters, the dependence of
      study parameters on the dropout patterns, and the use of the last observation
      carry forward, are also discussed.

PMID- 16440836
TI  - Optimal designs in stability studies.
AB  - New optimality criteria for stability studies are proposed, and the related
      optimal designs are investigated. For each optimality criterion, optimal designs
      are identified within a class of competing designs. The property of the optimal
      designs for detecting slope differences is discussed.

PMID- 16440837
TI  - Teaching statistical thinking to life scientists a case-based approach.
AB  - We describe a workshop on statistical thinking for scientists involved in
      pharmaceutical discovery research. The objectives were 1) to improve the quality
      of research data by developing a structured approach to bias and variability and
      2) to establish a collaborative and informed relationship between scientists and
      statisticians by broadening their common basis. The corner stone was the
      introduction of statistical thinking and the didactical route to achieve this
      goal.

PMID- 16440838
TI  - Quasi-empirical Bayes methodology for improving meta-analysis.
AB  - This article addresses the problem of heterogeneity among various studies to be
      combined in a meta-analysis. We adopt quasi-empirical Bayes methodology to
      predict the odds ratios for each study. As a result, the predicted odds ratios
      are pulled toward the estimated common odds ratio of the various studies under
      consideration. With strong heterogeneity among the studies, we jointly consider
      the display of the 95% CIs of the ORs and a Dixon's test (1950) for "outliers" to
      exclude the "extreme" estimated ORs. We demonstrate the effectiveness of our
      methodology based on the data analyzed by Thompson and Pocock (1987)
      demonstrating the power of the new approach to meta-analysis to find statistical
      agreement in what looks like great disagreement via a chi-squared test. We
      believe our technique (i.e., minimum mean-square sense) will go a long way toward
      increasing the trustworthiness of meta-analysis.

PMID- 16440839
TI  - Sample size determination for clinical trials in patients with nonlinear disease
      progression.
AB  - This paper provides explicit sample size determination formulas for planning a
      long-term trial in patients with chronic disease by using available results from
      existing short-term studies that may predict long-term disease progression
      patterns. The sample size calculation formulas are flexible to incorporate
      different nonlinear disease progression patterns. Various within-patient
      correlation structures are considered. By using the proposed formulas, sample
      size sensitivity can be easily explored for possible choices of study duration,
      assumed nonlinear disease progression patterns, randomization ratio, and expected
      clinical meaningful difference in the end of study. In addition, sample size
      calculation formulas are provided when the primary endpoint is change from
      baseline. Discussions on the relationship among required sample size, study
      duration, randomization ratio are also included.

PMID- 16440840
TI  - Conditional and unconditional confidence intervals following a group sequential
      test.
AB  - After a group sequential test, the naive confidence interval (CI) is usually
      biased in the sense that it does not cover the true parameter at the correct
      nominal level. Furthermore, when the stopping time is taken into account, the
      actual conditional confidence coverage probability can be much less accurate. In
      this article, we study the conditional coverage probability and other related
      properties of the naive CI and different versions of exact CI's. It is
      demonstrated that only correcting the overall confidence level does not
      necessarily improve the confidence level at any given stopping stage. Conditional
      inference can be applied to construct an exact conditional CI but it is not
      without serious undesirable properties. We propose a two-step restricted
      conditional confidence interval (RCCI) which considerably improves the
      conditional confidence level while minimizing the undesirable properties.
      Numerical comparisons are made between the proposed method and existing methods.
      The results show that the RCCI not only improves the conditional coverage
      probability considerably from the exact CI's but also is free of the major
      undesirable properties displayed by the pure conditional CI. Differences between
      the conditional and unconditional CI's and their respective strengths are also
      discussed.

PMID- 16440841
TI  - Parmacokinetic (PK) parameter Vss (volume in steady state) is superior or more
      reliable that Vz (the volume in the terminal state).

PMID- 16440842
TI  - The two cultures revisited.

PMID- 16440843
TI  - Lung functions with spirometry: an Indian perspective--II: on the vital capacity
      of Indians.
AB  - Spirometry has been used in India since 1929 to evaluate vital capacity. The mean
      value for this parameter has changed slightly for the better over about eight
      decades. It is currently recorded at about 21.8 ml/cm height for males and about
      18 ml/cm height for females, the difference between the two sexes being
      statistically significant throughout the period studied. The vital capacity
      reaches its peak at about 30 years of age in both Indian men and women and
      declines there after. There is no significant statistical difference in the vital
      capacities of subjects from different regions of India. Composite regressions
      have been generated for use as reference equations for estimating. Vital capacity
      of Indians is lower than that of Caucasians, but the age related decline is much
      greater for Caucasians.

PMID- 16440844
TI  - Mechanism of the immunomodulatory activity of glycodelin.
AB  - Glycodelin, a progesterone regulated protein synthesized by the endometrium (GdA)
      has been well documented to inhibit the proliferation of activated T-cells and is
      an indispensable molecule in the maternal system for the establishment,
      maintenance and progression of pregnancy. Data from our laboratory have
      unequivocally shown that the immunosuppression by GdA is via induction of
      apoptosis in activated T cells. Another isoform of glycodein, GdS, from the male
      reproductive system, in spite of sharing an identical amino acid sequence as that
      of GdA has been shown not to harbour the immunosuppressive activity of GdA. As
      the only difference between the two proteins is glycosylation, we proposed to
      study the role of the sugars in imparting apoptotic activity to Gd. Using the
      recombinant baculovirus system, Gd lacking glycosylation was expressed and from
      the experimental observations we could conclude that the activity of Gd lies in
      the protein backbone. Recombinant Gd expressed in P. pastoris, and Chinese
      hamster ovary cells, like the GdS did not exhibit apoptotic activity. A close
      analyses of the glycans associated with the Gd molecules from various sources
      suggested that though the apoptogenic activity of Gd lies in the protein
      backbone, the glycans modulate the activity by masking (as in case of GdS and
      most recombinant Gd expressed in our laboratory) or unmasking (as in case of GdA
      and baculovirus expressed Gd), the functional region of the molecule.

PMID- 16440846
TI  - Pharmacological studies of Clerodendron colebrookianum Walp, a potent hypotensive
      plant.
AB  - Clerodendron colebrookianum Walp., (Fam: Verbenaceae) locally known is "NEFAFU"
      is widely used for curing various diseases. Here some pharmacological properties
      of this plant were studied using rat & mice of either sex. Methanol extract (MLE)
      of various concentrations (50, 100, 200 mg/kg of body wt) were tested on animals.
      Carrageenin induced rat paw oedema model with three hours for oedema formation
      was used to test anti-inflammatory activity. It was observed that the plant
      extract significantly inhibits the Carrageenin induced rat paw oedema. The acetic
      acid induced writhing test by injecting 0.6% acetic acid (i.p.) followed by
      injecting MLE & tail immersion test, both in hot & cold water was used to test
      the analgesic effect of the plant. In all the four experiments MLE (200 mg/kg, of
      body wt.) has been found mostly effective in inhibiting Carrageenin induced rat
      paw oedema, the number of writhings induced by acetic acid & elevated pain
      threshold in hot & cold-water test. It reduced the number of abdominal writhing
      induced by acetic acid and elevated pain threshold in hot tail flick test. The
      effect of methanol extract (MLE) on phenobarbitone induced sleeping time was also
      tested, here again MLE (200 mg/kg of body wt) showed remarkable prolongation in
      sleeping time. Seasonal variation on the activities of the plant extract was also
      investigated in the study. The plant samples were collected in the months of
      January and July of the year. It has been observed that the January collection of
      the plant showed higher activities in most of the parameters in these experiments
      and also showed significantly higher values in the proximate analysis. The leaves
      of the C. colebrookianum were practically found to be non-toxic.

PMID- 16440845
TI  - Evaluation of possible goitrogenic and anti-thyroidal effect of nitrate, a
      potential environmental pollutant.
AB  - Nitrate is a wide spread contaminant of ground and surface water. The source of
      nitrate in the ground water may be from run off or seepage from fertilized soil,
      municipal or industrial waste water, land fills, septic system, urban drainage or
      decaying plants. Human and animal systems are affected severely on nitrate
      exposure. The study was to investigate the effect of dietary nitrate exposure on
      the thyroid status along with the state of iodine nutrition. Rats were fed diet
      containing 3% potassium nitrate (KNO3) for 4 weeks and then thyroid status was
      evaluated by thyroid gland weight, urinary iodine excretion pattern, thyroid
      peroxidase (TPO) activity, serum levels of total thyroxine (T4), triiodothyronine
      (T3) and thyroid stimulating hormone (TSH) concentrations. In nitrate treated
      animals, the weight of thyroid gland was increased significantly (P<0.001) while
      thyroid peroxidase activity (P<0.01), serum T4 (P<0.01) and serum T3 levels
      (P<0.001) were reduced; but serum TSH level was increased (P<0.001) along with
      slightly elevated iodine excretion level (P<0.001) in comparison to control
      animals. The overall results indicated the development of a relative state of
      functional hypothyroidism with enlarged thyroid after nitrate exposure. This
      study can explain a part for the persistence of residual goitre in the post-salt
      iodization phase.

PMID- 16440848
TI  - Study of anti-fertility effect of lemon seeds (Citrus limonum) in female albino
      mice.
AB  - Among the citrus species, Citrus-limonum is native of North West region of India.
      The petroleum ether, alcoholic and aqueous extracts of Citrus-limonum (lemon)
      seeds were investigated for anti-fertility effect in female albino mice. The
      extracts were administered orally for 7 days after insemination (i.e. post
      ovulatory test). The control group received 4% gum acacia. The animals were
      examined for implantation sites on 10th day of pregnancy and the number of pups
      delivered at term for each group was recorded. The alcoholic extract showed
      significant anti-fertility effect as compared to petroleum ether and aqueous
      extracts. The alcoholic extract was subjected for fractionation and the fractions
      were again tested for their anti-fertility effect. The fraction of ethyl-acetate
      (12-25 fractions) showed most encouraging anti-fertility activity. In second part
      of the study, the alcoholic extract and its ethyl-acetate fraction (12-25
      fractions) were subjected to evaluation of their mechanism of action and it was
      found that their principal mode of action is as an anti-zygotic agent. Withdrawal
      of the test drug, resulted in complete restoration of fertility. Thus the ethyl
      acetate fraction (12-25 fractions) of alcoholic extract of lemon seeds exerted
      reversible anti-fertility effect in female mice by virtue of its anti-zygotic
      action.

PMID- 16440847
TI  - Effect of exogenous lecithin on ethanol-induced testicular injuries in Wistar
      rats.
AB  - Infertility is well-established harmful effect in chronic alcoholism and so far,
      there is no effective treatment for this condition. The study was conducted to
      determine the effects of lecithin, a known hepatoprotective on ethanol induced
      testicular injuries in male albino rats of Wistar strain. Five groups (n=6) of
      animals were used. Group I served as control. Group II received daily 1.6 g
      ethanol/kg body weight/day for 4 weeks orally. Group III received 1.6 g ethanol +
      500 mg lecithin/kg body weight/day for four weeks orally. Group IV received 1.6 g
      ethanol/kg body weight for/day 4 weeks and followed by 500 mg lecithin/kg body
      weight/ day for four weeks orally. Group V received 1.6 g ethanol/kg body weight/
      day orally for 4 weeks, followed by 4 weeks abstinence. Twenty-four hours after
      the last treatment the rats were sacrificed using anesthetic ether. Testes were
      removed and used for the estimation of extent of lipid peroxidation and tissue
      levels of antioxidants and steroidogenic enzymes. Lecithin protected testes from
      ethanol induced oxidative stress. However, the drug did not show any considerable
      effect on the activities of testicular delta5, 3beta-HSD and 17beta-HSD. In
      conclusion, ethanol induced oxidative stress can be reversed by treatment with
      lecithin. However the effect of lecithin on steroidogenesis was not promising.

PMID- 16440849
TI  - Effect of slow and fast pranayams on reaction time and cardiorespiratory
      variables.
AB  - We planned to undertake a comparative study of the effect of short term (three
      weeks) training in savitri (slow breathing) and bhastrika (fast breathing)
      pranayams on respiratory pressures and endurance, reaction time, blood pressure,
      heart rate, rate-pressure product and double product. Thirty student volunteers
      were divided into two groups of fifteen each. Group I was given training in
      savitri pranayam that involves slow, rhythmic, and deep breathing. Group II was
      given training in bhastrika pranayam, which is bellows-type rapid and deep
      breathing. Parameters were measured before and after three week training period.
      Savitri pranayam produced a significant increase in respiratory pressures and
      respiratory endurance. In both the groups, there was an appreciable but
      statistically insignificant shortening of reaction time. Heart rate, rate
      pressure product and double product decreased in savitri pranayam group but
      increased significantly in bhastrika group. It is concluded that different types
      of pranayams produce different physiological responses in normal young
      volunteers.

PMID- 16440850
TI  - An investigation into the acute and long-term effects of selected yogic postures
      on fasting and postprandial glycemia and insulinemia in healthy young subjects.
AB  - The study was conducted to examine the hypothesis that yogasanas help in the
      treatment of diabetes mellitus by releasing insulin from the pancreas. Twenty
      healthy young voluntees (17 male, 3 female; age 19-31 years) participated in the
      study. Each volunteer performed four sets of asanas in random order for 5
      consecutive days each with a 2-day gap between consecutive sets of asanas. The
      four sets of asanas were: (I) dhanurasana + matsyendrasana, (II) halasana +
      vajrasana, (III) naukasana + bhujangasana, and (IV) setubandhasana +
      pavanamuktasana. Blood samples were collected on days 4 and 5 of each set of
      asanas for measurement of glucose and insulin levels before the asanas, within 10
      min after performing the asanas, and 30 min after ingestion of 75 g glucose,
      which in turn was ingested immediately after the second blood sample. A standard
      75 g oral glucose tolerance test (OGTT) was also done before and after the study.
      On the days of the pre-study or post-study OGTT, no asanas were done. The serum
      insulin levels after the asanas were lower (P<0.05) than those before the asanas.
      However, the serum insulin level 0.5 h after the post-asana oral 75 g-glucose
      challenge was higher (P<0.05) in Set IV than the 0.5 h postprandial insulin level
      in the pre-study OGTT; the same trend was observed in other sets as well although
      statistically not significant. The observations suggest that the performance of
      asanas led to increased sensitivity of the B cells of pancreas to the glucose
      signal. The increased sensitivity seems to be a sustained change resulting from a
      progressive long-term effect of asanas. The study is significant in that it has
      for the first time attempted to probe the mechanism by which yogasanas help
      diabetes mellitus.

PMID- 16440851
TI  - Gating of the dorsal penile nerve inputs by norepinephrine at the medial preoptic
      area in rats.
AB  - The medial preoptic area neurons related to male sexual behaviour in rats were
      identified by their responses to dorsal penile nerve stimulation. These neurons
      were further tested with norepinephrine applied iontophoretically. From the 21
      medial preoptic area neurons recorded in urethane anaesthetized rats, 17 neurons
      responded to dorsal penile nerve stimulation. Excitatory and inhibitory responses
      were found in almost equal number of neurons. 14 neurons responded to
      norepinephrine application, out of which six neurons were excited and eight were
      inhibited. The direction of changes produced by dorsal penile nerve stimulation
      and norepinephrine application were similar in 10 neurons. The results suggest
      that the sensory inputs from the genitalia are possibly gated by norepinephrine
      at the level of the medial preoptic area. Afferent information from the genitalia
      carried by dorsal penile nerve and the availability of norepinephrine at the
      level of the medial preoptic area probably help in maintaining adequate level of
      sexual arousal.

PMID- 16440852
TI  - L-ascorbic acid ameliorates postnatal endosulfan induced testicular damage in
      rats.
AB  - The aim of the present study is to investigate the effect of L-ascorbic acid on
      postnatal exposure of endosulfan induced testis damage in the rat. Four groups of
      seven day old male Wistar rats were treated with 3, 6, 9 and 12 mg/kg endosulfan
      orally (10 pups/group), from postnatal day 7 to 60 at intervals of 24 h. For 2
      more groups (n = 10/group), endosulfan (9 mg/kg and 12 mg/kg) was administered
      along with L-ascorbic acid (20 mg/kg). The sperm morphology, sperm count and
      sperm motility was analyzed in all the groups on postnatal day 70. Endosulfan
      significantly affected the testicular function enhancing the incidence of
      abnormal spermatozoa, decreasing the sperm count and sperm motility in a dose
      dependent manner. Abnormalities were of both head and tail and increase in their
      frequency was more than two-fold of the control value. Sperm count abruptly
      decreased in 12 mg/kg group and sperm motility decreased up to 50% of the control
      value. L-ascorbic acid has nullified the toxic effects of the pesticide
      significantly, but not to the control level. Endosulfan induces the testicular
      damage following postnatal exposure and L-ascorbic acid prevents the adverse
      effects considerably in the rat.

PMID- 16440853
TI  - Effect of anticholinesterase compound phosalone on blood-brain barrier (BBB)
      permeability.
AB  - To elucidate the role of acetylcholinesterase (AChE) enzyme in BBB function,
      phosalone, an organophosphorous compound, was studied using rat brain micro
      vessels in vitro. Phosalone at 100 mg/kg b. wt. induced convulsions and caused a
      significant inhibition of AChE resulting in increased permeability as assessed by
      volume distribution. The anaesthetized phosalone treated group also increased
      permeability as compared to the control but the values were significantly
      (P<0.05) lower than phosalone alone treated group. The inhibition of AChE enzyme
      has altered the barrier function at the dose level at which it caused convulsion
      and had an added effect on permeability of BBB.

PMID- 16440854
TI  - Serum copper, ceruloplasmin, protein thiols and thiobarbituric acid reactive
      substance status in liver cancer associated with elevated levels of alpha
      fetoprotein.
AB  - Serum copper, ceruloplasmin, protein thiols and thiobarbituric acid reactive
      substances (TEARS) were estimated in 25 patients of liver cancer. The copper to
      ceruloplasmin ratio was moderately increased (P<0.05) but the copper (P<0.001)
      and ceruloplasmin (P<0.001) levels were significantly increased in liver cancer
      patients when compared to controls. Protein thiols levels were found to be highly
      significant (P<0.001). Where as the TEARS levels were not found to be
      significant. Trace elements and free radicals have been implicated in the
      etiology of cancer. Hence the estimation of ceruloplasmin and protein thiols
      along with the copper may be of high value in the early diagnosis of cancer.

PMID- 16440855
TI  - Differential effects of exogenous estrogen versus a estrogen-progesterone
      combination on auditory evoked potentials in menopausal women.
AB  - The study was undertaken to determine the differential effects of estrogen and
      progestin on auditory evoked responses in postmenopausal women receiving hormone
      replacement therapy (HRT). Forty-seven women between 45 and 70 years of age
      attending menopause and HRT clinic were divided into two groups. Group I included
      32 women who attained natural menopause and receiving combined estrogen progestin
      therapy. While group II included 15 surgically menopausal women receiving only
      estrogen. Evoked potentials were recorded in form of auditory brainstem response
      (ABR), middle latency response (MLR) & slow vertex response (SVR). There was
      improvement of conduction in auditory pathways at the level of brainstem and
      thalamocortical projections as indicated by the decrease in latencies of most of
      the waves of ABR and/MLR after 6 months of HRT in both the groups. The conduction
      in association areas, as indicated by SVR, did not show a significant change. The
      intergroup comparison after therapy revealed a decrease in latency of wave V and
      I-V interpeak latency in group II indicating that only estrogen users are
      benefited more. Thus HRT facilitates the process of sensory conduction, which may
      form one of the mechanisms of improved neuropsychological functions in menopausal
      women on HRT. The addition of progestin to estrogen does not have a negative or
      potentiating effect on it.

PMID- 16440856
TI  - Cardiorespiratory fitness of obese boys.
AB  - Childhood obesity is increasing worldwide and may be linked to coronary heart
      diseases that appear later in life but its risk related behaviour patterns are
      evident during childhood and adolescence. The present study aimed to evaluate the
      cardiorespiratory fitness in terms of maximum oxygen uptake (VO2max) in obese
      boys of West Bengal, India. Obese boys (N = 49) in the age range of 10-16 years
      were separated from their non-obese counterparts (N = 70) according to
      international age-wise cut off points of body mass index (BMI) and VO2max was
      evaluated by Queen's College Step Test (QCT). Lean body mass (LBM) was measured
      by skinfold method. Absolute VO2max was significantly higher (P<0.001) among
      obese boys because of higher values of body mass and LBM, which in turn exhibited
      significant correlation (r = 0.82 and r = 0.93, respectively; P<0.001) with
      VO2max. But VO2max per kg of body mass was significantly higher among non-obese
      boys but the VO2max per unit of body surface area was significantly higher
      (P<0.001) in obese group. VO2max is largely dependent on body mass and LBM
      whereas excessive fat mass imposes unfavourable burden on cardiac function and
      oxygen uptake by working muscles. This indicates that reduced oxygen utilization
      by adipose tissue during exercise reduces the overall VO2max.

PMID- 16440857
TI  - Effect of a comprehensive yoga-based lifestyle modification program on lipid
      peroxidation.
AB  - Oxidative stress contributes to the process of aging as well as a variety of
      chronic degenerative diseases. There are indications that psychological stress
      increases oxidative stress whereas relaxation decreases it. We have measured the
      concentration of thiobarbituric acid reactive substances (TBARS) in blood as an
      indicator of oxidative stress at the beginning and at the end of a comprehensive
      yoga-based lifestyle modification program (YLMP). The data was collected from 104
      subjects (59 male, 45 female), 19-71 years of age (mean +/- SD, 41.2 +/- 14.6
      years). The YLMP consisted of a nine-day educational out-patient course on the
      theory and practice of yoga and included, besides a daily one-hour practice of
      physical postures (asanas) and breathing exercises (pranayama), lecture and films
      on yoga, stress management and nutrition, practice of meditation and shavasana (a
      relaxation technique), and individual counseling. Venous blood samples were
      collected on the first and last day of the course. The serum concentration of
      TBARS decreased significantly from 1.72 +/- 0.72 nmoles/ml on day 1 to 1.57 +/-
      0.72 nmoles/ml on day 10 (P<0.05). The study suggests that a brief low cost
      lifestyle intervention based on yoga reduces oxidative stress.

PMID- 16440858
TI  - Probing the anti-hyperlipidemic efficacy of the allspice (Pimenta officinalis
      Lindl.) in rats fed with high fat diet.
AB  - In this study, the anti-hyperlipidemic effect of aqueous extract of Pimenta
      officinalis (APO) was investigated in experimental rats fed with high fat diet
      (HFD). Hyperlipidemia in experimental rats was evidenced by a significant
      enhancement in the level of glycerol, triglycerides and phopholipids in serum,
      and also in liver and kidney tissues. HFD caused oxidative stress in these
      animals as shown by marked increment in the levels of thiobarbituric acid
      reactive substances (TBARS) and diene conjugates (CD), and a distinct diminution
      in reduced glutathione (GSH) content in liver and kidneys. Antioxidant enzymes
      such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase
      (GPX) showed reduced activity in hyperlipidemic rats. All these biochemical
      parameters showed reliable signs of retrieving towards near-normalcy in APO
      administered HFD fed rats. This study unveiled the anti-hyperlipidemic as well as
      antioxidant activity of APO.

PMID- 16440859
TI  - Status of iodine deficiency amongst school children in twenty four districts in
      southern India.
AB  - The central legislation banning sale of non-iodized salt for edible purposes in
      the entire country was withdrawn by the Government in the year 2000. The present
      study was conducted in the year 2001 immediately after lifting the central ban to
      establish the baseline urinary iodine excretion levels in twenty four districts
      of Southern India. In each district all the senior secondary schools were
      enlisted and one school was selected by random sampling. About 120 children in
      the age group of 11 to 18 years were selected using the random number tables. The
      urinary iodine excretion levels were analysed using the wet digestion method. It
      was found that districts Rangareddy, Kolar, Yanam and Perambalour had median UIE
      levels less than 100 microg/l, indicating iodine deficiency. The findings of the
      present study highlights the success of Universal salt iodisation programme. The
      Government of India should reinitiate the process of central ban on sale of non
      iodised salt in the country to prevent the iodine deficiency disorders.

PMID- 16440860
TI  - Erb's palsy after delivery by Cesarean section. (A medico-legal key to a vexing
      problem.).
AB  - Despite impressive progress in perinatology, fetal injuries from arrest of the
      shoulders at birth have not decreased in recent decades. Based upon sporadic
      reports of Erb's palsy in neonates born by Cesarean section, some obstetricians
      embraced the theory recently that brachial plexus lesions often derive from
      spontaneous forces acting in utero. Having reviewed three hundred malpractice
      claims involving fetal injuries attributed to shoulder dystocia at birth, the
      authors found only two cases connected with abdominal deliveries. One followed
      manual replacement of the already delivered fetal head into the pelvis after
      sequential vacuum and forceps procedures and failed manual extraction of the
      body. The other was an elective repeat Cesarean section where extensive adhesions
      limited the available space for the lower segment transverse uterine incision.
      Coincidental fracture of the clavicle and absence of contractures or deformities
      indicated that the brachial plexus injury was acute, having resulted from
      forceful traction at delivery.

PMID- 16440861
TI  - Terminally ill infants, parents and the courts.
AB  - Parents sometimes demand 'full active treatment' for a terminally ill child, even
      against medical advice. They think that they should decide their child's best
      interests, not medical staff, who may conclude too readily that the child's life
      is 'not worth living'. Only parents who know and love their child can decide
      that. Doctors and nurses, on the other hand, feel they have the training and
      experience to assess the pain and distress of heroic measures and whether they
      are justified in cases where a child cannot survive, or will have profound
      disability. This paper reviews recent case law in the United Kingdom and
      Australia on the role and processes of courts where a hospital (or a parent)
      applies for a court order regarding treatment. The author concludes that it is
      possible but unlikely that a court would direct medical staff to provide
      treatment they regard as clinically inappropriate.

PMID- 16440862
TI  - Criminal prosecution arising from medical mishaps: a Japanese perspective.
AB  - In Japan, the number of physicians being investigated on suspicion of medical
      malpractice has increased. Specifically, the criminal prosecutions arising from
      professional negligence resulting in bodily injury or death have also increased.
      Article 21 of the Japanese Physician's Act compels a doctor to notify the
      district police when he diagnoses a death to be 'unnatural'. Originally this
      provision was to increase public safety through crime detection, but one recent
      criminal case broadened the application of this article to include the death from
      a mishap during medical treatment. This criminal case made a tremendous impact on
      physicians, as the convictions and sentences forced physicians to notify the
      police even when it is not certain the patient died of the malady or of the
      medical misconduct itself. Besides, we wonder if such obligation of doctors to
      notify such 'unnatural' death from medical mishap may be against a person's
      privilege against self-incrimination which is assured by Japanese Constitutional
      Law (article 38).

PMID- 16440863
TI  - Healthcare regulation in the UK: part two performance, conduct and health.
AB  - In 2000, the UK Government published the NHS (National Health Service) Plan, an
      ambitious ten year programme promising to deliver a patient-centred service, more
      healthcare professionals and other resources, and greater redress for patients
      who perceive their treatment within the NHS to be substandard. These strands,
      higher standards of healthcare with a more consumerist patient focus and greater
      accountability, have given rise to the creation of new bodies setting standards,
      auditing performance, developing greater patient participation in the national
      and local health care agenda plus complete revamping of the regulatory bodies and
      the establishment of a new umbrella body to regulate the regulators.

PMID- 16440864
TI  - The debate on no-fault compensation in the Netherlands.
AB  - In the Netherlands the total number of liability claims per year is about 2500,
      100 of which are taken to court. Over the years these figures appear to be rather
      constant. It has been estimated that introducing a no-fault compensation system
      would lead to three to six times as many claims and would push up the costs of
      medical malpractice claims by a factor of three or even seven. When considering
      the introduction of a no-fault compensation system the main question to be
      answered is which problem has to be solved. Is it the improvement of the
      patients' possibility to recover? Is the main goal to put a stop to the progress
      of increasing costs of liability claims? Is saving doctors from the threat of
      being sued the main issue? Or is there a problem of the insurance companies that
      has to be solved? No-fault compensation is not a panacea. In the end improving
      the liability system may turn out to be a better solution.

PMID- 16440865
TI  - Some ethical dilemmas faced by Jewish doctors during the Holocaust.
AB  - The discourse on physicians and ethics in the Nazi regime usually refers to the
      violation of medical ethics by Nazi doctors who as a guild and as individuals
      applied their professional knowledge, training and status in order to facilitate
      murder and medical "experimentation". In the introduction to this article I will
      give a brief outline of this vast subject. In the main article I wish to bear
      witness to the Jewish physicians in the ghettos and the camps who tried to the
      best of their ability to apply their professional training according to ethical
      principles in order to prolong life as best as they could, despite being forced
      to exist and work under the most appalling conditions. These prisoner doctors
      were faced with impossible existential, ethical and moral dilemmas that they had
      not encountered beforehand. This paper addresses some of these ethical quandaries
      that these prisoner doctors had to deal with in trying to help their patients
      despite the extreme situations they found themselves in. This is an overview of
      some of these ethical predicaments and does not delve into each one separately
      for lack of space, but rather gives the reader food for thought. Each dilemma
      discussed deserves an analysis of its own in the context of professionalism and
      medical ethics today.

PMID- 16440866
TI  - The practice of applying compulsory treatment to mentally disturbed people: a
      view from Russia.
AB  - The author describes the development of current legislation in Russia relative to
      compulsory medical treatment for mentally ill persons. He discusses these laws in
      relation to criminality and its prevention.

PMID- 16440867
TI  - Experience with practice guidelines for medico-legal death investigations: the
      case of falls-related deaths in hospital.
AB  - Western philosophical and political thought has focussed on the significance of
      individual relativism. The legal system's approach to the investigation and
      regulation of medical practice is generally ad hoc and based on case law. In
      contrast, medical knowledge and understanding is progressively shifting towards a
      system of taxonomies and norms. Clinical guidelines and evidence-based medical
      practice are now commonplace in clinical practice. Due to the polarity of
      professional frameworks underpinning medicine and law, there has been an on-going
      struggle for the successful use of medical law that benefits both the quality of
      medical practice as well as its practitioners. This paper discusses the
      principles in developing and implementing a standard investigation tool for the
      coronial sector using the Falls Investigation Standard as an example, which has
      been in use for 12 months in the state of Victoria, Australia. It is hoped that
      using a standardised tool can balance the often conflicting tensions between
      medical and legal sectors by enabling an in-depth review of each issue while also
      strengthening the health system's capacity for self-regulation.

PMID- 16440868
TI  - Parental access to minors' health records in the South African health care
      context: concerns and recommendations.
AB  - Privacy and confidentiality have long been recognised as essential elements of
      the doctor-patient relationship. Patients should feel free to disclose the most
      intimate and private medical facts about themselves to their physicians in order
      to facilitate optimal patient care. Medical records, whether hand-written or
      electronic, also play an important role in other contexts, such as medical
      research, health care management and financial audit. In South Africa there is
      little consistency in approaches to patient confidentiality. There are also no
      national standards or policies on patient confidentiality, apart from specific
      ethical rules, some ad hoc statutory provisions and general constitutional
      provisions not directly related to the intricacies of the doctor-patient
      relationship. A closer look at the relevant statutory provisions reveal the
      existence of conflicting standards, most notably in respect of parental access to
      a minors' health records. The purpose of this paper is to examine the
      discrepancies and contradictory provisions relating to the access to and
      disclosure of health information, in particular parental access to health records
      of minors. In the final instance, some recommendations will be suggested.

PMID- 16440869
TI  - Sex selection: intergenerational justice or injustice?
AB  - Arguments surrounding the issue of sex selection focus on the potential, negative
      outcomes of permitting such choices. In this article, it is argued that--rather
      than being negative--sex selection (particularly for, but not confined to, family
      balancing reasons) can be a positive reflection of the reproductive liberties
      which have been won over the last century. It is accepted that this argument
      applies most clearly in cultures where there is no overt preference for one sex
      over another, but in those societies where this does not apply, it is equally
      unlikely that the concept of reproductive choice is valued. The article argues
      that permitting intending parents to choose the sex of their child--while likely
      to be a relatively rare event--is in line with the concept of intergenerational
      justice, in that it may serve not just the interests of intending parents but
      also those of the children to be born.

PMID- 16440870
TI  - Genetic screening and reproductive choice: is making a child to save another
      unethical?
AB  - During 2002, the Human Fertilization and Embryology Authority (HFEA) in England,
      which regulates in vitro fertilization (IVF) clinics, agreed to allow a family to
      attempt to create a baby genetically selected to help treat a desperately ill
      child. The media reaction against this HFEA decision has shown profound outrage,
      expressing that having a child for the sake of the other is improper, immoral and
      'against human dignity'. Other claims were, "we should protect vulnerable human
      life", and "human beings should not be treated 'as a means to an end"'. None of
      these moral claims however, stand rational and coherent scrutiny. Thus, this
      paper maintains that making a child to save the life of his brother is not only
      ethically permissible but it would rather be unethical NOT to do so.

PMID- 16440871
TI  - The examination of genetic characteristics since the adoption of the French law
      on bioethics.
AB  - The French bioethics law of July 1994 was due to be revised five years after its
      enactment. It was not until 6 August 2004, that the revised law was finally
      adopted. The examination of the genetic characteristics of a person may only be
      undertaken for medical purposes or for the purposes of scientific research.
      Consent must therefore be obtained in writing, after fully informing the patient,
      and may be withdrawn at any time, in either form (orally or in writing). French
      law nevertheless authorises carrying out such an examination where there is no
      consent, solely for medical purposes and in the interest of the patient. The
      issue has arisen of the detection of a serious genetic anomaly during an
      examination of genetic characteristics. In this respect, certain anomalies may
      lead to the patient's relatives being tested, in order to suggest suitable
      treatment. A procedure for informing families has been implemented by the French
      Biomedicine Agency (details of which will be specified in a decree).

PMID- 16440872
TI  - The killing of severely disabled newborns: the spectre behind the legalisation of
      physician-assisted suicide and euthanasia.
AB  - Arguments made by those in favour of the legalisation of physician-assisted
      suicide (PAS) and euthanasia often rely upon the idea of the quality of life.
      This idea states that an individual's life is not valuable as an intrinsic good,
      but is only good based upon the things which it allows us to do. It thus allows
      the argument that it is morally permissible to kill individuals whose lives have
      fallen below an acceptable 'quality of life.' However, this concept may require
      that one accept the killing of individuals who have not expressly request to be
      killed such as severely disabled newborns. This paper will examine the issue of
      whether those who utilise a quality of life approach to justify the legalisation
      of PAS and euthanasia must logically accept the policy of killing severely
      disabled newborn children. First, there will be an examination of the concept of
      quality of life and its importance in the arguments for the legalisation of PAS
      or euthanasia. This paper will then consider how notions of personhood interact
      with the concept of quality of life in order to create the problem faced by those
      who favour the legalisation of PAS or euthanasia. Finally, this paper will
      consider how the notion of autonomy may be used as a way to avoid this difficulty
      created by the quality of life approach.

PMID- 16440873
TI  - Assessment procedures regarding end-of-life decisions in neonatology in the
      Netherlands.
AB  - This paper describes the position of Dutch law concerning end-of-life decisions
      in neonatology consequent on rulings of the Dutch appeals court in two cases. The
      concept of a multidisciplinary assessment committee is explored. The European
      Convention on Human Rights in its articles 2 and 13 is relevant to this concept.
      The author provides a detailed discussion of the current situation and draws
      conclusions based on his perception of future developments in regulating thanatic
      practices in neonatology.

PMID- 16440874
TI  - Bridges to life: evaluation of an in-prison restorative justice intervention.
AB  - Restorative justice initiatives have been identified as primarily, if not
      exclusively, useful as a "front-end" diversionary option reserved for non violent
      property crimes and minor assaults. In-prison restorative justice programs are
      rare and have not been examined for their impact on recidivism. Bridges to Life
      (BTL) is a voluntary, manualized, ecumenical faith-based restorative justice
      program offered to incarcerated offenders who are within nine months of their
      release. A survey of BTL graduates (n=1021) found an appreciatively lower
      recidivism rate than the general population of released inmates. Quantitative and
      qualitative analyses suggest that BTL helps break through offenders' denial and
      self-centeredness, exposing them to the impact of their actions and helping them
      feel the pain their crimes created. Possible reasons for the positive nature of
      participants' responses are advanced. The use of in-prison restorative justice
      programs to facilitate offender re-entry is also discussed.

PMID- 16440875
TI  - Harmful and unethical pressure on psychiatrists as a consequence of governments'
      policies.

PMID- 16440877
TI  - Mandibuloacral dysplasia: a report of two Egyptian cases.
AB  - Mandibuloacral dysplasia (MAD) is a rare disorder. Only 35 patients, coming from
      22 families, have been reported worldwide. We report on two Egyptian unrelated
      girls with MAD. The first patient presented at the age of 5 years with acral
      defect and partial alopecia. The second patient presented at the age of 17 years
      with progressive micrognathia and loss of subcutaneous fat from the limbs.
      Physical examination detected the craniofacial, skeletal and cutaneous changes
      characteristic of MAD. Both patients were short with progeroid facies and loss of
      subcutaneous fat from the extremities, which fits lipodystrophy type A pattern.
      Radiological examination revealed delayed closure of cranial sutures, hypoplastic
      mandible, hypoplastic clavicles, and acroosteolysis. Both patients had normal
      glucose tolerance, but had fasting and post-prandial hyperinsulinemia, suggestive
      of insulin resistance. One patient had elevated serum triglycerides and low
      normal cholesterol levels, while the other patient had normal levels. Serum
      leptin was normal in both patients. We review the literature on mandibuloacral
      dysplasia and discuss the differential diagnosis.

PMID- 16440876
TI  - Attitudes towards carrier testing in minors: a systematic review.
AB  - The objective of this article is to review the attitudes of the different
      stakeholders (minors, healthcare professionals, parents and relatives of affected
      individuals) towards carrier testing in minors. The databases Pubmed, Google
      Scholar, Psychinfo, Biological Abstracts, Francis, Anthropological Index online,
      Web of Science, and Sociological Abstracts were searched using key words for the
      period 1990-2004. Studies were included if they were published in a peer reviewed
      journal in English and described the attitudes of minors, parents or healthcare
      professionals towards carrier testing in minors in a family context. The results
      were presented in a summary form. In total 20 relevant studies were retrieved (2
      studies reported the attitudes of two stakeholders). Only one study reported the
      attitudes of adolescents, two studies reported the attitudes of adults who had
      undergone carrier testing in childhood. In total six studies have been retrieved
      discussing the parental attitudes towards carrier testing in their children. Over
      all studies, most parents showed interest in detecting their children's carrier
      status and responded they wanted their child tested before the age of majority:
      some parents even before 12 years. Eight studies were retrieved that reported the
      attitudes of relatives of affected individuals. Most were in favor of carrier
      testing before 18 years. The studies retrieved suggest that most parents are
      interested in the carrier status of their children and want their children to be
      tested before they reach legal majority (and some even in childhood). This can
      lead to tensions between parents and healthcare professionals regarding carrier
      testing in minors. Guidelines of healthcare professionals advise to defer carrier
      testing on the grounds that children should be able to decide for themselves
      later in life to request a carrier test or not.

PMID- 16440878
TI  - Fryns syndrome without diaphragmatic hernia. Report on a new case and review of
      the literature.
AB  - Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome
      characterized by coarse facies, diaphragmatic hernia, distal limb hypoplasia and
      malformations of the cardiovascular, gastrointestinal, genitourinary and central
      nervous systems. Diaphragmatic hernia is a leading diagnostic feature in Fryns
      syndrome, recorded in more than 80% of cases. We report a newborn with clinical
      features of Fryns syndrome except the diaphragmatic hernia. Cases of Fryns
      syndrome without diaphragmatic hernia are reviewed. Even in the absence of
      diaphragmatic hernia, pulmonary anomalies are described in Fryns syndrome,
      especially pulmonary hypoplasia. Fetal mice, exposed to nitrofen, have a high
      incidence of congenital diaphragmatic hernia and other malformations similar to
      that seen in Fryns syndrome. Nitrofen might target molecular mechanisms similar
      to those involved in Fryns syndrome.

PMID- 16440879
TI  - Chromosomal region 13q21q31 and heterochrony of development.
AB  - If the theory of evolution is now largely accepted, there are still many debates
      on the mechanisms of evolution, including human evolution. One of these
      mechanisms is heterochrony of development including progenesis and neoteny. We
      report on a patient who could be an example of human progenesis. This boy was
      born prematurely, after a cesarian section for preeclampsia. Family history was
      unremarkable. He walked unaided when he was 2.5 years old. At 5 years of age
      height was 95 cm (< 3rd centile), weight 18.6 kg (40th centile) and OFC 54 cm
      (98th centile is 53 cm). He had a macropenis. He attended elementary school.
      However, at 9 years of age he had to have special education. Puberty occurred
      when he was 8 years old. At 14 years of age height was 141 cm (3rd centile is 144
      cm), weight 32.5 kg (3rd centile) and OFC 55.5 cm (75th centile). At physical
      examination he had hypertelorism, narrow forehead, short philtrum,
      retromicrognathia, large and low set ears, hyperlaxity, overcrowed teeth, dorsal
      kyphosis, and macropenis. Karyotype showed a deletion 13q21q31. The deletion was
      de novo and pure. In conclusion this case with sexual precocity and small final
      stature could be an example of progenesis, rising the question of the presence of
      a critical region for human evolution within chromosomal region 13q21q31.

PMID- 16440880
TI  - Thrombocytopenia-absent radius (tar) syndrome: a case with agenesis of corpus
      callosum, hypoplasia of cerebellar vermis and horseshoe kidney.
AB  - The thrombocytopenia-absent radius (TAR) syndrome (MIM 274000) is a congenital
      malformation syndrome characterised by bilateral absence of the radii with
      present thumbs, hypomegakaryocytic thrombocytopenia and a number of additional
      features including skeletal and cardiac anomalies. Mental retardation, reported
      in about 7% of patients, is usually secondary to intracranial hemorrhage. In 1994
      there was a single report of a girl with TAR syndrome and hypoplasia of the
      cerebellar vermis and corpus callosum and in 2003 another case of TAR syndrome
      with cerebellar dysgenesis has been reported. In 2000 there was first report of
      horseshoe kidney in association with TAR syndrome followed by a clinical study of
      34 cases with TAR syndrome in 2002 where horseshoe kidney was noted in two cases.
      Here we report of a girl with TAR syndrome, severe mental retardation, agenesis
      of corpus callosum, hypoplasia of cerebellar vermis and horseshoe kidney. There
      is no previous report of a child with TAR syndrome and all those associated
      anomalies in the same patient.

PMID- 16440881
TI  - Abilities and needs of children with genetic syndromes.
AB  - Children with unbalanced karyotypes or other genetic syndromes are generally
      supposed to be developmentally retarded and mentally handicapped. This has to be
      ascribed to defect oriented views, leading to negative valuations of their
      unusual physical condition including slow motor development. A new dialogue
      oriented view and working concept is presented. It accepts physical differences
      as biological facts, which primarily do not restrict brainpower. The development
      of intelligence, behaviour and personality depends largely on the environment.
      Impeding factors should be searched here and eliminated as far as possible with
      the aim to prevent secondary mental disability after a syndrome diagnosis. In
      general, children with genetic syndromes are able to understand language. Thus,
      they can be educated like other children. They should learn to accept rules and
      limits, answer questions and follow demands. Their communicative tools may be
      words, gestures, mimics or written language. While physical support has to be
      given if necessary, their principally open mind needs stimuli according to their
      chronological age. Normal mental capacities should be expected, unless the
      opposite is proven.

PMID- 16440882
TI  - Double aneuploidy in three Egyptian patients: Down-Turner and Down-Klinefelter
      syndromes.
AB  - The co-occurrence of two numerical chromosomal abnormalities in same individual
      (double aneuploidy) is relatively rare and its clinical presentations are
      variable depending on the predominating aneuploidy or a combination effect of
      both. Furthermore, double aneuploidy involving both autosomal and sex chromosomes
      is seldom described. In this study, we present three patients with double
      aneuploidy involving chromosome 21 and sex chromosomes. They all had the
      classical non disjunction trisomy 21; that was associated with monosomy X in two
      of them and double X in the other. Clinically, they had most of the phenotypic
      features of Down syndrome as well as variable features characteristic of Turner
      or Klinefelter syndrome. Cytogenetic studies and fluorescence in situ
      hybridization (FISH) analysis were carried out for all patients and their
      parents. The first patient was a male, mosaic with 2 cell lines (45,X/47,XY,+21)
      by regular banding techniques and had an affected sib with Down syndrome
      (47,XY,+21). The second was a female, mosaic (46,X,+21/47,XX,+21) where monosomy
      X was detected only by FISH in 15 percentages of cells, nevertheless, stigmata of
      Turner syndrome was more obvious in this patient. The third patient had non
      mosaic double trisomy; Down-Klinefelter (48,XXY,+21) presented with Down syndrome
      phenotype. Parental karyotypes and FISH studies for these patients were normal
      with no evidence of mosaicism. In this report, we review the variable clinical
      presentations among the few reported cases with the same aneuploidy in relation
      to ours. Also, the proposed mechanisms of double aneuploidy and the occurrence of
      non-disjunction in more than one family member are discussed. This study
      emphasizes the importance of molecular cytogenetics studies for more than one
      tissue in cases with atypical features of characteristic chromosomal aberration
      syndromes. To our knowledge, this is the first report of double aneuploidy, Down
      Turner and Down-Klinefelter syndromes in Egyptian patients.

PMID- 16440883
TI  - Apert syndrome with preaxial polydactyly showing the typical mutation Ser252Trp
      in the FGFR2 gene.
AB  - The Apert syndrome is characterized by craniosynostosis and syndactyly of hands
      and feet. Although most cases are sporadic, an autosomal dominant mode of
      inheritance is well documented. Two mutations in the FGFR2 gene (Ser252Trp and
      Pro253Arg) account for most of the cases. We report a patient with a rare form of
      Apert syndrome with polydactyly. The proposita has turribrachycephaly. complete
      syndactyly of 2nd to 5th digits ("mitten hands" and cutaneous fusion of all
      toes). The X-rays revealed craniosynostosis of the coronal suture and preaxial
      polydactyly of hands and feet with distal bony fusion. Molecular analysis found a
      C755G transversion (Ser252Trp) in the FGFR2 gene. Only eight patients with Apert
      syndrome and preaxial polydactyly have been reported and this is the first case
      in which molecular diagnosis is available. On the basis of the molecular findings
      in this patient, polydactyly should be considered part of the spectrum of
      abnormalities in the Apert syndrome. This assertion would establish the need for
      a new molecular classification of the acrocephalopolysyndactylies.

PMID- 16440884
TI  - Partial trisomy 9q syndrome with a de novo tandem duplication of 9q22.2-q31.1.
AB  - A female with a de novo tandem duplication of 9q22.2-q31.1 is presented.
      Molecular delineation of the breakpoints was made by microarray CGH and
      fluorescent in situ hybridisation. Involvement of 9q22.2-q31.1 seems to be
      sufficient to produce the characteristic phenotype of partial trisomy 9q
      syndrome. A discussion on the recognizable clinical features of the condition is
      presented.

PMID- 16440885
TI  - Unilateral congenital absence of the lunate and scaphoid.
AB  - We report a patient with unilateral absence of the scaphoid and lunate bone of
      the wrist. Remarkably he had severe osteoarthritis in several other joints.

PMID- 16440886
TI  - Rehabilitation needs of a genetic counseling unit.

PMID- 16440887
TI  - Congenital contractural arachnodactyly, brachydactyly and sensorineural hearing
      loss: an unusual association.

PMID- 16440888
TI  - Antenatally diagnosed acrocallosal syndrome with intact corpus callosum: second
      affected offspring.

PMID- 16440889
TI  - Distal 3p monosomy associated with epilepsy in a boy.

PMID- 16440890
TI  - Windblown foot: a particular presentation of Proteus syndrome?

PMID- 16440891
TI  - Terminal distal 13q trisomy due to de novo dup(13)(q32 --> qter).

PMID- 16440892
TI  - [The effect of polyester vascular prostheses on synthesis TNF-alpha, IFN-gamma
      and NO by human peripheral blood leukocytes--in vitro].
AB  - Vascular prostheses produced on the basis of polyester are today commonly used in
      vascular surgery. To improve their biofuncionality special technologies are used,
      among them double knit and hydrophile feature enrichment. These modifications
      could cause the local activation of leukocytes to produce the mediators of
      inflammatory reaction, which in turn leads to hyperplasia of endothelium and
      other dangerous complications. In our study we used two kinds of polyester
      prostheses: double velour knitted hydrophilic Dallon H and standard double velour
      knitted prosthesis Dallon as control. The aim of this work was to compare in
      vitro the levels of cytokines TNF-alpha, interferon (IFN) and nitric oxide (NO)
      found in the supernatants of human blood leukocyte cultures after stimulation by
      both these above-mentioned vascular prostheses materials which are designed for
      use in direct blood contact. Tested implant materials Dallon H had no influence
      on synthesis of production of IFN, TNF-alpha and NO by human blood leukocytes.
      These results allow to made the initial selection of biomaterials before their in
      vivo evaluation.

PMID- 16440893
TI  - [Evaluation of short-time resorption surgical sutures in tubal anastomoses with
      use of microsurgical techniques. An experimental study].
AB  - In the paper there have been evaluated synthetic absorbable surgical sutures-
      Coated VICRYL, of short time of their resorption in an organism. The valuation
      concened their usefulness to carrying out the operations of oviducts with use of
      microsurgical technique. It consisted in determination of biocompatibility degree
      of analyzed sutures within tubal tissues and also their technical utility to this
      kind of procedures. The valuation of the surgical sutures was performed on the
      ground of experimental studies with use of laboratory animals--New Zealand white
      female rabbits, in which "end-to-end" microsurgical tubal anastomoses were made,
      with use of analyzed sutures. In further stage, pathomorphological investigations
      of the animals were performed (in various time after the operation), during which
      there were conducted microscopic observations of histologic slides derived from
      tubal anastomoses regions. The purpose of the work was trying to appoint the most
      adequate suture material for carrying out the operations of oviducts with use of
      microsurgical technique. It was also an assistance for an operator to take a
      decission of choice of the proper surgical sutures for surgical treatment of
      female mechanical infertility and other kind of microsurgical operations which
      are performed in gynaecology. Generally good technical utility in microsurgical
      practice of surgical sutures Coated VICRYL--absorbable of short period of their
      resorption in tissues was stated. They cause the formation of only single
      peritoneal adhesions, mainly in the regions of tubal anastomoses previously made
      and produce relatively small tubal tissue reaction, which testifies to high
      biocompatibility of the sutures, as the implantation material. The analyzed
      surgical sutures characterize themselves of very good usefulness to microsurgical
      operations of oviducts.

PMID- 16440894
TI  - [Concentration influence of some polymers on dermatological hydrogels pH].
AB  - For last two decades there is a lot interest in skin pH research, and pH
      influence on the skin barrier function. A wide range of hydrophilic polymers are
      applied worldwide for topical and transdermal preparation, influencing acid
      mantle of the skin. One of the determinants for feasibility of the polymer for
      dermatological application, and for proper drug release kinetics is the pH. The
      aim of the work was pH determination of some polyacrylic acid hydrogels and
      methylcellulose hydrogels in different concentrations. Carbopol 934 pH was 2.473
      to 3.682 in concentrations between 0.1% and 2.0%. In the same concentrations
      carbopol 971 was in the range of 2.923 and 3.862, and carbopol 980 reached the
      values 2.638-3.763. pH of methylcellulose gels in the range 0.1%-2.0% was 5.136
      7.265. Methylcellulose gels were at the higher physiological skin pH rate, and
      the polyacrylic gels ranged in rather acidic pH. Determined hydrogen ion
      concentration was a function of polymer concentration, also in the case of
      nonionic polymer concentration--similar to a logarythmic function. Stable polymer
      dispersion pH values were reached after determined time, following statistical
      consideration.

PMID- 16440895
TI  - The application of aqueous solutions of products of alternating oxypropylene- and
      oxyethylenating n-ols as a solubilizer for selected sterols.
AB  - The process of equilibrium solubility of sterols (cholesterol, cholic acid,
      hydrocortisone) by aqueous solutions of Rokanols was investigated. Critical
      micellar concentration (cmc) and thermodynamic potential of micellarization
      (deltaG(m)0) were determined for aqueous solutions of Rokopols RF-55, RF-33, TG
      500 and R-330. The solubility activity of aqueous solutions of Rokopols was
      defined by calculation from the viscosity measurements of solubility index n(sol)
      for cholesterol, cholic acid and hydrocortisone. The amount of solubilized
      hydrocortisone by Rokopol micelles was determined by a spectrophotometric method.

PMID- 16440896
TI  - Selected Rofams as a micellar solubilizers for diclofenac and naproxen in the
      environment of the standard vehicle for eye drops.
AB  - The process of the equilibrium solubilization of nonsteroidal anti-inflammatory
      drugs (NSAID), viz. diclofenac and naproxen, by Rofams, ie. the products of the
      oxyethylenating of the rape oil fatty acid methyl esters, in the environment of
      water solutions NaCl 9 g/l, H3BO3 19 g/l, KNO3 16 g/l, was tested. The
      solubilization activity of Rofam aqueous solutions was estimated with the use of
      the spectrophotometric method by means of the determination of the amount of the
      solubilized NSAID. The calculated apparent solubility of Rofam aqueous solutions
      was the basis for the estimation of the micellar partition coefficient K(w)m. The
      course of the ratio of the solubilized naproxen and diclofenac in the function of
      the solubilizer (Rofam R-13, R-15, R-17) exposure concentration was described by
      means of approximative equations with a high correlation coefficient.

PMID- 16440897
TI  - Possibilities of application of non-ionic surfactants belonging to Rofam, Rokopol
      and Rokanol class in the prescription of dental anti-inflammatory gels.
AB  - Belonging to the classes of: Rofams, Rokopols and Rokanols were used to form the
      gels soap base. The model gels extensibility was investigated by extensometric
      method, while their viscosity parameters were determined with cone-plate digital
      rheometer. Regardless of the applied gel vehicle, model prescriptions of dental
      anti-inflammatory gels with sodium ibuprofen have been worked out. Natural
      polysaccharides: xanthan gum, tragacanth, guar gum were the vehicles of the
      formed gels. New non-ionic surfactants the most beneficial results of rheological
      measurements were obtained for model gels with Rofam R-15. The calculated areas
      under extensibility curves of preparations with Rofam R-15 are greater than for
      gels with Rokopol RF55 or Rokanol OC9. Introduction of Rofam R-15 into the
      prescription is associated with maintenance of low value of yield stress. When
      this value is exceeded under the effect of slight shear, the gel does not stay
      long on the surface of its application. High values of theoretical coefficients
      of sodium ibuprofen diffusion from gels with Rofam R-15, calculated from Einstein
      Smoluchowski equation, are the consequence of their low viscosity. The carried
      out in vitro comparative testing of the kinetics of sodium ibuprofen release from
      the gel with Rofam R-15 and from gel with sodium estolate of parallel
      prescription did not demonstrate any basic differences in the size of the areas
      under the release curves (14,4046 and 13,5308 c.u. for the vehicle with xanthan
      gum).

PMID- 16440898
TI  - [Clinical and radiographic evaluation of Bio-Oss for the treatment of periodontal
      intra-bony defects--6 months study].
AB  - Intra-bony defects remain a significant therapeutic problem in periodontal
      theraphy. Periodontal surgery with various bone grafts is being used. The aim of
      the study was clinical and radiographic evaluation of 6 months treatment efects
      following periodontal surgery with grafting procedures with Bio-Oss Spongiosa and
      Bio-Oss Collagen. The following clinical parameters were evaluated: probing
      pocket depth, clinical attachement level and gingival recession. Radiographic
      assessment included defect depth, width and radiographic Engelberger, Marthaler
      and Rateitschak index. Treatment was performed in 40 defects: 16 one-walled, 21
      two-walled and 3 three-walled. Statistic analisis was carried out using t-tests.
      The follow-up examination performed 6 months following surgery found a statistic
      significant reduction of probing pocket depth and gain in clinical attachement
      level as well as reduction of radiographic defects depth and width and increase
      of radiographic Engelberger, Marthaler and Rateitschak index.

PMID- 16440899
TI  - Best of times for the best of leaders. Healthcare management opportunities
      continue to be rewarding.

PMID- 16440900
TI  - Achieving real results with Six Sigma. "Six Sigma to the rescue," declared the
      title of a June 2002 article in the technology section of Health Care Finance.
      Almost four years later, has Six Sigma helped healthcare organizations achieve
      the promised breakthrough improvement in their operations?

PMID- 16440901
TI  - Seeing the future: innovative supply chain management strategies.

PMID- 16440902
TI  - Becoming more effective patient advocates: beyond empathy. Changing the attitude
      and behavior of healthcare professionals toward patients should not require
      walking in their shoes, but the invaluable insights provided by having the
      personal experience of being a patient are both undeniable and insufficient.

PMID- 16440903
TI  - Must I maintain another person's promise? Weighing how decisions affect
      stakeholders in the hospital.

PMID- 16440904
TI  - Can CT scans be 'fun'? Innovative CT suite gives children greater control over
      the environment to ease their fears.

PMID- 16440906
TI  - Health information technology: tentative federal and congressional developments.

PMID- 16440905
TI  - Professional chaplaincy: establishing a hospital-based department.

PMID- 16440907
TI  - The benefits of mentoring. Explore opportunities at ACHE.

PMID- 16440908
TI  - Governance at the crossroads. Outside trustees are enriching community-based
      boards.

PMID- 16440910
TI  - Do all patients with suspected appendicitis benefit from CT imaging in community
      based emergency departments?

PMID- 16440909
TI  - Strengthening support for your physicians. Physician leaders want and need
      support--but how can executives provide it?

PMID- 16440911
TI  - The art and science of diagnosing acute appendicitis.

PMID- 16440913
TI  - Atypical presentations of Sjogren disease.

PMID- 16440912
TI  - Environmental influences on diet and physical activity in childhood:
      opportunities for intervention.

PMID- 16440914
TI  - Brucella glomerulonephritis.

PMID- 16440915
TI  - The threat of malaria for US travelers.

PMID- 16440916
TI  - An outcome study of the use of computed tomography for the diagnosis of
      appendicitis in a community-based emergency department.
AB  - OBJECTIVES: Previous studies evaluating the use of CT in the diagnosis of
      appendicitis have taken place at university-based institutions where surgical
      bedside consultation seems prudent before radiological study. In the private
      hospital setting, the emergency department (ED) physician is responsible for
      diagnosis. We attempt to assess if this process is detrimental to patient care.
      METHODS: Retrospective review of 150 patient's records admitted through the ED
      was performed with the discharge diagnosis of appendicitis between March 1998 and
      May 2000. Data was stratified for analysis based on age (< 15, 15-50, > 50) and
      gender. Using Graph Pad Prism software the groups were compared for complications
      based on whether or not CT was obtained. Chi-square, number needed to treat
      (NNT), absolute risk reduction (ARR), relative risk reduction (RRR) and
      respective confidence intervals were calculated for each group. RESULTS: No
      significant differences overall were obtained between CT and no CT groups at P <
      0.05. A significant benefit is demonstrated at P = 0.017 in females of
      childbearing age while a detrimental trend is found for those over the age of 50
      years. CONCLUSIONS: Contrary to our initial hypothesis, no increased incidence of
      appendiceal perforation or abscess was demonstrated based on the ED physician's
      decision to perform CT without surgical consultation.

PMID- 16440917
TI  - Effectiveness of a school-based intervention to increase health knowledge of
      cardiovascular disease risk factors among rural Mississippi middle school
      children.
AB  - BACKGROUND: Few school-based interventions have been evaluated to assess health
      awareness among children in rural southern areas. The purpose of this controlled
      investigation was to increase health awareness among middle school-aged children
      residing in a racially diverse rural community in Mississippi. METHODS: This
      investigation assessed health knowledge before and after a 16-week school-based
      intervention in 205 fifth-grade students. Height, weight, BMI, body composition,
      waist circumference, dietary intake, blood lipids and lipoprotein concentrations,
      blood glucose concentrations, and resting blood pressure were measured to enhance
      student awareness of cardiovascular disease risk factors. Values in the
      intervention school were compared with those obtained simultaneously in a control
      school within the same community. RESULTS: The school-based intervention was
      effective in increasing health knowledge in the intervention as compared with the
      control school. Secondarily, it was effective in improving certain dietary
      behaviors. Utilizing health care professionals in the classroom to teach students
      appropriate lifestyles and actually measuring cardiovascular risk factors to
      increase awareness among students was effective in increasing overall health
      knowledge. CONCLUSIONS: Health knowledge of rural adolescents can be increased
      through partnerships with schools and multidisciplinary teams of health care
      professionals. Ongoing efforts to reduce childhood obesity and cardiovascular
      disease risk factors are urgently needed, and information obtained during this
      investigation may be used in planning school-based interventions in other
      diverse, rural communities.

PMID- 16440918
TI  - Factors that affect parental disciplinary practices of children aged 12 to 19
      months.
AB  - BACKGROUND: Physicians are encouraged to provide counseling regarding parental
      discipline. Quality counseling requires knowledge of disciplinary practices and
      factors that affect these practices. METHODS: One hundred and eighty two parents
      of 12- to 19-month-old children from general pediatric clinics in North Carolina
      and Alabama were interviewed regarding discipline using the Discipline Survey.
      Measures of contextual factors were analyzed to see which predicted disciplinary
      practices. RESULTS: Ninety-two percent of the participants were mothers; 6% were
      fathers; participation rate: 78%. Monitoring was the most common type of
      discipline used and time out was the least common. Parent, child, and family
      characteristics were all importantly associated with a broad array of
      disciplinary practices and modes of administration. However, the situation in
      which discipline occurred was found to be significant for most disciplinary
      practices even after controlling for other factors. Our study found that the
      specific misbehavior was most likely, and the presence of the other parent was
      least likely, to affect the type of discipline which was utilized. CONCLUSIONS:
      When counseling families about discipline, practitioners should incorporate the
      fact that misbehavior happens in various contexts.

PMID- 16440919
TI  - The effect of sunless tanning on behavior in the sun: a pilot study.
AB  - BACKGROUND: In the United States, indoor tanning is a booming industry and
      contributes to the ultraviolet light (UVL) burden that ultimately leads to skin
      cancer. "Sunless" tanning methods that avoid UVL exposure may represent a safe
      alternative. However, the effects of sunless tanning methods on ultraviolet light
      related behaviors have never been investigated. METHODS: Anonymous survey of 121
      individuals who underwent a spray-on sunless tanning treatment between February
      and May 2004. RESULTS: Women completed 107 surveys. Men completed 14 surveys. The
      majority of individuals reported that they had not or would not change their time
      spent outdoors or their sunscreen use as a result of undergoing sunless tanning.
      However, 73% of individuals who had used UVL tanning beds said they had decreased
      or would decrease their UVL tanning bed use. CONCLUSION: Sunless tanning is
      associated with a self-reported decrease in traditional UVL tanning bed use among
      tanning bed users. Physicians should advocate the use of sunless tanning to their
      patients who use traditional UVL tanning beds as a means of decreasing their UVL
      exposure and cancer risk.

PMID- 16440920
TI  - Malaria primer for clinicians in the United States.
AB  - Though low, the incidence of malaria in the United States is not insignificant
      and can be the source of infection in febrile travelers returning from endemic
      areas. Clinicians practicing in the United States must have a basic understanding
      of the malaria life cycle and its treatments to properly diagnose and treat this
      potentially fatal disease. Malaria chemotherapy can be broken into clinical
      classes for easier understanding, and any traveler to a malaria-endemic region
      should be placed on prophylactic medications. Mosquito bite prevention should be
      undertaken by all travelers, and methods of deterring mosquito bites should be
      understood.

PMID- 16440921
TI  - Pinch-an-inch test for appendicitis.
AB  - Rebound tenderness is a widely used examination technique for patients with
      suspected appendicitis, but it can be quite uncomfortable. An alternative test
      for peritonitis is termed the "pinch-an-inch" test. This report describes two
      patients who presented with mild abdominal pain who subsequently were found to
      have appendicitis. In both patients, classic peritoneal signs were absent, but
      the pinch-an-inch test was positive. The experienced physician's bedside clinical
      examination remains the most critical component for rapidly identifying
      peritonitis. Although rebound tenderness is a widely used examination, it is
      uncomfortable and may be inaccurate. To perform the pinch-an-inch test, a fold of
      abdominal skin over McBurney's point is grasped and elevated away from the
      peritoneum. The skin is allowed to recoil back briskly against the peritoneum. If
      the patient has increased pain when the skin fold strikes the peritoneum, the
      test is positive and peritonitis probably is present.

PMID- 16440922
TI  - Unusual presentation of Sjogren syndrome.
AB  - This case report describes a patient with Sjogren syndrome (SS) whose sole
      presenting feature was bilateral and painful submandibular gland enlargement.
      Extensive workup for alternate etiologies was negative and while serologies
      specific for SS were unremarkable, the diagnosis was eventually suggested by
      excisional biopsy. This case highlights the difficulty in making an early
      diagnosis of SS and demonstrates the important role of excisional biopsy in that
      diagnosis.

PMID- 16440923
TI  - Unusual cause of hypokalemic paralysis in aged men: Sjogren syndrome.
AB  - Hypokalemic paralysis is a less recognized but reversible disorder in elderly
      patients. This report describes two elderly Chinese males (age 74 and 78 years)
      who had progressive muscle weakness and eventually paralysis. Physical
      examination showed symmetrical flaccid paralysis of extremities. Both had the
      major biochemical abnormality of profound hypokalemia (1.4 and 1.8 mmol/L)
      accompanied by high urine K+ excretion and hyperchloremic metabolic acidosis. A
      positive urine anion gap and alkaline urine pointed to the diagnosis of distal
      renal tubular acidosis. Large doses of potassium chloride supplementation were
      required to restore muscle strength. Pertinent investigations, including elevated
      titers of antinuclear antibody and rheumatoid factor, positive anti-Ro antibody,
      low serum C3 and C4 levels, and delayed saliva excretion on salivary scintigraphy
      suggested Sjogren syndrome. Despite the lack of sicca syndrome at the initial
      presentation, both had development of typical sicca syndrome and positive
      Schirmer test at the 5-month and 1-year follow-up, respectively. Potassium
      citrate supplement and prednisolone therapy completely corrected the hypokalemia
      and metabolic acidosis. Extraglandular involvement with distal renal tubular
      acidosis preceding the typical sicca syndrome may induce hypokalemic paralysis
      and unveil Sjogren syndrome in elderly males.

PMID- 16440924
TI  - Brucella glomerulonephritis: case report and review of the literature.
AB  - The authors present the case of a 17-year-old shepherd who was diagnosed with
      diffuse proliferative glomerulonephritis and diffuse tubulointerstitial nephritis
      during the course of Brucella infection. The pathogenesis and the mechanism of
      renal involvement in brucellosis is discussed in light of the pertinent
      literature.

PMID- 16440925
TI  - Eosinophilic pleural effusion, peripheral eosinophilia, pleural thickening, and
      hepatosplenomegaly in sarcoidosis.
AB  - In this atypical case of sarcoidosis with an unusual combination of clinical and
      laboratory findings, a 32-year-old male presented with a 3-month history of
      thoracic pain complicated with dyspnea. Laboratory tests, chest radiography, and
      CT scans of the chest and abdomen revealed eosinophilia of pleural effusion and
      blood, pleural thickening, hepatosplenomegaly, and bronchiolitis obliterans. In
      cases such as this, in which pleural fluid eosinophilia is accompanied by
      peripheral eosinophilia and splenohepatomegaly, underlying malignancies such as
      Hodgkin lymphoma should be ruled out. A biopsy of the mediastinal lymph nodes
      suggested noncaseating epithelioid granulomas, characteristic of sarcoidosis. The
      patient underwent prednisolone therapy for 1 year and is doing well 2 years after
      initial diagnosis.

PMID- 16440926
TI  - Response to determining functional significance of subclavian artery stenosis
      using exercise thallium-201 stress imaging.

PMID- 16440927
TI  - Pyomyositis of the iliacus muscle in an adolescent.

PMID- 16440928
TI  - Spontaneous Escherichia coli meningitis with subdural empyema in an adult.

PMID- 16440929
TI  - Quinupristin-dalfopristin-induced reticulocytopenic anemia.

PMID- 16440930
TI  - Rituximab is effective in the treatment of refractory immune thrombocytopenic
      purpura associated with chronic lymphocytic leukemia.

PMID- 16440931
TI  - Malignant fibrous histiocytoma, malignant melanoma and squamous cell carcinoma
      arising from different areas in an adult.

PMID- 16440933
TI  - The patient's page.

PMID- 16440932
TI  - Colistin-associated acute renal failure: revisited.

PMID- 16440934
TI  - Religion, spirituality and medicine: the beginning of a new era.

PMID- 16440935
TI  - Clergy as health care providers.

PMID- 16440936
TI  - Definition of terms: spirituality versus religiousness.

PMID- 16440937
TI  - Physician's perspective combining spirituality and medicine: one physician's
      approach.

PMID- 16440938
TI  - Debate question: should physicians incorporate spirituality into the care of
      patients?

PMID- 16440939
TI  - What do we know about the effectiveness of faith-based health programs?

PMID- 16440940
TI  - Partnering together? Relationships between faith-based community health centers
      and neighborhood congregations.
AB  - OBJECTIVE: The US Bureau of Primary Health Care has promoted collaboration
      between federally funded community health centers and neighborhood religious
      congregations, yet little is known about how such organizations currently
      interact in underserved neighborhoods. METHODS: Semistructured interviews were
      conducted with leaders from five faith-based, urban community health centers and
      23 neighborhood congregations. Transcripts were coded for prevalent concepts and
      themes regarding collaborations between the two types of organizations. RESULTS:
      Collaborations between health centers and congregations are generally limited to
      modest sharing of resources and personnel and intermittent health promotion
      programs. Leaders of both types of organizations desire greater collaboration,
      but such desires appear to be frustrated by inadequate resources and differing
      priorities, visions, and philosophies. CONCLUSIONS: Increased collaboration
      between community health centers and neighborhood congregations will require
      efforts to overcome organizational differences, intercongregational tensions, and
      resource limitations. For the participants, comprehensive "faith partnerships"
      remain a desirable but elusive goal.

PMID- 16440941
TI  - Religious awareness training for medical students: effect on clinical
      interpersonal behavior.

PMID- 16440942
TI  - [Nursing doctoral theses produced on graduate programs between 1983-2001].
AB  - This study describes the relationship between nursing doctoral dissertations and
      research lines defined by the Brazilian Nursing field in three areas:
      professional, care and organizational. It isa descriptive-exploratory research,
      based on reports of Graduate Programs evaluated by CAPES and on The Informative
      Guide of Nursing Research and Researchers CEPEn/ ABEn, from 1983 to 2001,
      totalling 448 abstracts. The care field includes the greatest production,
      followed by the organizational and professional areas. The studies disclose
      tendency towards the qualitative approach revealing possibilities for a more
      profound knowledge about reality or a more through understanding of social
      phenomena related to nursing practice. On the other hand, studies on
      interventions in professional practice and technological development are still
      under construction.

PMID- 16440943
TI  - [The history of the nursing interunits doctoral program and its contribution to
      Brazilian nursing].
AB  - Authors aimed at describing the history of the Nursing Interunits Doctoral
      Program offered at the Sao Paulo and Ribeirao Preto campi from 1981 to 2004. Data
      were collected based on the Program documents (resolutions, opinion, students'
      records, reports, etc). The Nursing Interunits Doctoral Program was approved by
      the University of Sao Paulo Graduate Council in May 25, 1981. During the past
      several years, until the beginning of the 1990s, the demand was centered in the
      students from the Schools responsible for the Program, followed by faculty from
      other Nursing Schools in Brazil. The Program has resulted in the formation of
      researchers from different Brazilian and South American Universities, leading the
      creation of research groups and originating new graduate programs.

PMID- 16440944
TI  - [Doctoring interunits in nursing program: 21 years building science].
AB  - The Doctoring Interunits in Nursing Program was the first created in Latin
      America and has titled 290 nurses until the second semester of 2004. This study
      presents some thesis characteristics upheld in the program, focusing the thematic
      areas and research methods used. The summaries of 287 theses supported until the
      first semester of 2004, have been analyzed. The most investigated fields up to
      now were: Children, Woman, Adult/ Elderly Health and Education. The quantitative
      research method predominated until the end of the 80's, since then an intense
      production of qualitative method researches started to occur. Still in the first
      decade of the program, the themes started to talk about the aspects that connect
      the practice of nursing to the political and social contexts, converging to the
      current program's paradigmatic axis: "Theoretical, philosophical, historical
      bases of knowledge and of the nursing practice."

PMID- 16440945
TI  - [The University of Sao Paulo, School of Nursing's history of graduate program].
AB  - It reports the history of creation and development of the graduate program at
      this School, as well as participation the first group of advisers, since the
      creation of the masters' course in 1973. Research sources were documents and data
      registration at the Graduate Program's secretariat, publications, and also the
      living memory of some faculty members. Evolutions occurred with the creation of
      the doctoral program, the increasing of the study fields and its expansion to
      other institutions outside of the Sao Paulo State are presented as well as the
      identification of the nurse-pioneers doctors who they formed giving origin to the
      second generation of doctors in nursing, who in their turn formed other masters
      and doctors of the third generation, and so successively, conforming a true
      genealogical tree of masters and doctors

PMID- 16440946
TI  - [The production of knowledge in the field of management of nursing services in
      the Graduate Program in Nursing].
AB  - The study at hand had as an objective the identification and analysis of the
      production of knowledge in the field of Management of Nursing Services, in the
      Master and Doctorate Courses of the Graduate Program at the Nursing School of the
      University of Sao Paulo. It is an exploratory, descriptive, retrospective and
      documentary study. The population was constituted of 128 scientific productions,
      namely, 102 (79.7%) master dissertations and 26 (20.3%) doctorate theses produced
      between 1977 and March 2004. These works were analyzed according to theme groups
      in the proposed categories. Results allowed us to visualize the distribution of
      that production in terms of theme, decade, method and lines of thought adopted in
      such works. Results also allowed us to make considerations as to the
      trajectories, needs and perspectives of research in Nursing Management within the
      Program.

PMID- 16440947
TI  - [Building knowledge in collective health: an analysis of thesis and
      dissertations].
AB  - The aim of this study was to analyze scientific production in Collective Health
      developed by Collective Health Nursing Department of the School of Nursing Sao
      Paulo University within 1992 and 2004. A total of 86 master dissertations and
      doctoral thesis were produced, concerning a variety of study objects, mainly
      epidemiologic profiles and social reproduction, connected to health-illness
      processes of social groups. Qualitative analysis predominated, as well as the
      historical and dialectical theoretical referential. Empirical data were obtained
      predominantly from different social groups of specific territories. The adoption
      of analytical categories such as social production and reproduction, gender and
      generation enabled approaching to comprehend and propose intervention on the
      study objects, thus improving Collective Health scientific knowledge.

PMID- 16440948
TI  - [The knowledge produced in the graduate program in nursing: psychiatric nursing].
AB  - After almost 30 years since the creation of the Psychiatric Nursing Concentration
      Area in the Graduate Program of the University of Sao Paulo Nursing School, it is
      important to take a look at its scientific production in order to substantiate
      reflection about teaching. This is a descriptive-exploratory study. It used as
      sources the registers of the Graduate Service, abstracts from theses and
      dissertations, and memoranda and official correspondence. The data collected were
      analyzed in the light of the transformations occurred in this structure that has
      graduated 60 students, of which 50 obtained a Master's Degree and 10 a PhD, and
      that has been restructuring its disciplines, research lines and projects with the
      objective of responding to internal and external evaluations and adjusting to the
      guidelines of the country's fostering agencies. Current scientific production
      points out to an alignment with the guidelines of the Psychiatric Reform, and a
      tendency to produce knowledge through the concrete practice of the workers in the
      assistance field, the mana-gement and the teaching of Mental Health.

PMID- 16440949
TI  - [The adult health graduate area in nursing and its cognitive resource
      mobilization].
AB  - This study analyses the scientific production of the adult health between 1994
      and 2002, showing the potentialities of the process of cognitive development in
      researchers in the Nursing area. It also identifies the challenges for answering
      the theoretical dialogues between the generative matrix of different life, health
      and illness expressions, which is the aim of its faculty.

PMID- 16440950
TI  - [Students profile and academic production of the Adult Health Nursing Graduate
      Program].
AB  - The aim of this study was to evaluate the profile of the students and the
      knowledge produced in theAdult Health Nursing Graduate Program (PROESA) of the
      Nursing College of the University of Sao Paulo (EEUSP). A documental, exploratory
      and descriptive study from 2000 to 2004 was conducted. Results identified that
      the students of the PROESA in the period analyzed were graduated at the EEUSP
      (46.5%), they had a long time as nursing practitioners and no previous experience
      in scientific research. It were concluded 43 academic production (2.4 production/
      sponsor) and the principal area of investigation was "Technology in adult
      health". The research designs of most quantitative studies were classified as non
      intervention with a high frequency of descriptive studies. The long time to
      accomplish the publication and the restricted assort of qualified journals in
      nursing areas were the most important identified factors to limit the
      publications of the academic production.

PMID- 16440951
TI  - [Scientific knowledge as a value in the nurse's acting].
AB  - This study with the objective to know the as values that supports the action of
      the nurse. It was a qualitative research based on hermeneutic. Data were obtained
      by means of an interview recorded by eight nurses working at the Hospitalization
      Units of the Hospital Sao Paulo. By means of the meaning obtained from speeches,
      it was possible to identify knowledge scientific a mean to obtain safety in the
      acting and to assure power.

PMID- 16440952
TI  - [Nursing human resources from the perspective of workforce: an analysis of the
      scientific production].
AB  - The focus of this research is on human resources in nursing, particularly from
      the perspective of workforce. The objectives are to identify the national
      scientific production on human resources in nursing, analyze particularly those
      publications about workforce in nursing, and give a historical perspective on the
      composition of nursing workforce and the distribution of nursing workers
      throughout the country. In this bibliographic research LILACS, PeriEnf, DEDALUS,
      BDENF, PAHO, MS, ADSAUDE, ENSP, FSP, TEXTOC and SIDORH's databases were
      consulted, as well as CEPEn's catalogues, from 1958 to 2001. 469 publications
      were identified: 345 (73,6%) utilized human resources in nursing as a descriptor,
      while 79 (16,8%) and 45 (9,6%) utilized, respectively, the keywords nursing
      workforce (FTE) and nursing work market. There is a higher concentration of
      scientific production in the second half of the 80's and throughout the 90's.

PMID- 16440953
TI  - [The use of work process category for Brazilian nurses: a bibliographic
      analysis].
AB  - The aim of this study was to identify, in bibliographic production, how Brazilian
      nurses have been discussed "work process" in nursing practice. The bibliographic
      research was realized in Lilacs, in a period from January of 1993 to December of
      2003, and focus the periodics: Acta Paulista de Enfermagem, Nursing (SP), Revista
      Brasileira de Enfermagem, Revista da Escola de Enfermagem da USP, Revista
      latinoamericana de Enfermagem e Revista Texto e contexto de Enfermagem. The key
      words used were: process and work and care; process and work and nursing. The
      results show that is small the bibliographic production that using "work process"
      like a category of analysis of nursing practice, and there are a concentration of
      this production in articles that focus tools of nursing work In this study were
      find 40 articles and the most of them was published in Revista Brasileira de
      Enfermagem in the year of 2000.

PMID- 16440954
TI  - Novel haemostatic techniques in military medicine.

PMID- 16440955
TI  - Reporting clinical activity on military operations--time for some
      standardisation.

PMID- 16440956
TI  - 'Physiological' 0.9% saline in the fluid resuscitation of trauma.

PMID- 16440957
TI  - Specialist physiotherapists in orthopaedic triage--the results of a military
      spinal triage clinic.

PMID- 16440958
TI  - "Military Medicine in the 21st Century": Exercise Triple Serpent 2005.

PMID- 16440959
TI  - A review of 10 years of systematic health surveillance in the Army.
AB  - Health and morbidity reporting has been an important feature of the historical
      assessment of military campaigns from times of antiquity. Most of these reports
      have concentrated on hospital admission rates and mortality. In 1994 the British
      Army introduced a primary care health surveillance reporting system called J94.
      This provided the first opportunity for the systematic capture and analysis of
      morbidity data that allowed the identification of disease trends and the audit of
      remedial action. In parallel with the developments made by the military in the
      field of health surveillance, a number of initiatives in the NHS tried to develop
      real time surveillance systems with differing degrees of success. This paper
      reviews the developments made by military and civilian programs, identifies the
      problems that have been faced, areas where success has been achieved and the
      issues that will have to be considered as we prepare for the introduction of the
      next generation of IT based medical information systems into the military.

PMID- 16440960
TI  - Incidence of SLAP lesions in a military population.
AB  - OBJECTIVES: SLAP (superior labrum anterior and posterior) lesions are a
      recognised cause of shoulder pain and instability. They can occur following a
      direct blow, biceps traction and compression injuries, and are commonly seen in
      overhead athletes. Military personnel are physically active and often subjected
      to trauma. We assessed the incidence of SLAP lesions within a military population
      presenting with shoulder symptoms. METHODS: A retrospective review, of all
      shoulder arthroscopies performed by a single surgeon between June 2003 and
      December 2004 at a district general hospital serving both a military and civilian
      population, was undertaken. The presentation and incidence of SLAP lesions were
      recorded for both military and civilian patients. RESULTS: One hundred and
      seventy eight arthroscopies were performed on 70 (39.3%) military and 108 (60.7%)
      civilian patients. The average age was 42.3 (range 17-75), 50 females and 128
      males were included. Indications for arthroscopy included pain (75.3%),
      instability (15.7%), pain and instability (7.9%), or "other symptoms" (1.1%). 39
      SLAP lesions (22%) were found and grouped according to the Snyder classification-
      20.5% type 1, 69.3% type 2, 5.1% type 3, 5.1% type 4. Patients with a history of
      trauma or symptoms of instability were more likely to have a SLAP lesion
      (p<0.0001). The incidence of SLAP lesions in the military patients was 38.6%
      compared to 11.1% in civilian patients (p<0.0001). After allowing for the
      increased incidence of trauma and instability in the military, SLAP lesions were
      still more common in the military patients (p<0.001). CONCLUSIONS: There is a
      higher than average incidence of SLAP lesions in military patients compared to
      civilian patients. They tend to present with a history of trauma, as well as
      symptoms of pain and instability. Given the high incidence in military personnel,
      this diagnosis should be considered in military patients presenting with shoulder
      symptoms, and there should be a low threshold for shoulder arthroscopy.

PMID- 16440961
TI  - Evaluation of clinician attitudes to the implementation of novel haemostatic
      techniques.

PMID- 16440962
TI  - Management of unstable cervical spine injuries in southern Iraq during OP TELIC.
AB  - INTRODUCTION: Cervical spine fractures and dislocations are uncommon injuries
      that can have serious neurological consequences. These injuries require adequate
      stabilisation to prevent further spinal cord injury during transfer between
      hospitals. Evacuation often requires a combination of road ambulance, helicopter
      and fixed wing aircraft from military hospitals. This paper outlines the neck
      injuries sustained during Op Telic and discusses the need for Halo vests to be
      available at Role 3. METHODOLOGY: The MND(SE) Hospital databases were used to
      identify all casualties admitted with either a "Cervical" or "Neck" injury. The
      databases covered the period from 24 March 2003 until 15 April 2004. The
      diagnoses were categorised into minor and serious cervical spine injuries. We
      defined a serious cervical spine injury as either a fracture or dislocation. We
      looked at the discharge letters of all casualties evacuated to a Role 4 hospital
      to confirm whether the casualties had serious cervical spine injuries. RESULTS:
      Forty seven casualties were admitted and all were British except three, two Iraqi
      civilians and one US soldier. Thirty three casualties were returned to their unit
      for duty, or discharged at the airhead on return to the UK. Fourteen casualties
      required hospital treatment. There were five serious cervical spine injuries over
      the study period which included one Hangman's fracture of C2, one flexion
      compression injury of C5, one flexion compression injury of C7, one unifacetal
      dislocation and one bifacetal dislocation. CONCLUSIONS: Five casualties were
      treated at MND(SE) Hospital for serious injuries to the cervical spine. Two
      patients were transferred without Halo stabilisation after failing to obtain
      halos in Iraq. One casualty was kept until a Halo was flown out from the UK.
      RECOMMENDATIONS: All unstable cervical spine fractures should be stabilised with
      a Halo Vest prior to transfer from Role 3. Halo Rings and Vests should be
      available at Role 3 facilities.

PMID- 16440963
TI  - Forward surgery on Operation Telic--Iraq 2003.
AB  - Two Air Assault Surgical Groups (AASGs) from 16 Close Support Medical Regiment
      deployed to Kuwait on Operation Telic in February 2003. Each AASG was comprised
      of a four-table resuscitation facility, a two table FST and a twin-bedded ITU
      facility. An A+E Consultant and nurse, an experienced radiographer and laboratory
      technician with two further RGNs and CMTs provided resuscitation support. Each
      FST had an orthopaedic and a general surgeon, two anaesthetists and eight
      operating department practitioners. Further equipment consisted of a Polymobil
      111 X-ray unit, a Sonosite 180 ultrasound scanner and an ISTAT gas, haematocrit
      and electrolyte analyser. 100 units of mixed blood were carried by each AASG.
      Fifty-one surgical procedures were performed on thirty one patients. Twenty one
      of these patients were Iraqi prisoners of war or civilians. Seventeen wound
      debridements, five amputations, five laparotomies, four insertions of Denham pins
      with Thomas splintage for femoral fracture, three external fixations and one
      axillary artery repair formed the basis of the major cases undertaken. The first
      field use of activated factor VII by the British Army was successful in the
      resuscitation of a patient with exsanguinating haemorrhage after an open-book
      (APC-III) pelvic fracture and a ruptured intrapelvic haematoma. The other cases
      included eleven manipulations under anaesthetic/application of plaster and four
      finger terminalisations. Forward military surgery has a continued role to play on
      the modern fast moving battlefield. 16 Close Support Medical Regiment normally
      supports 16 Air Assault Brigade with its remit for expeditionary operations and
      SF support. Its experience on Op Telic should influence planning for future
      deployment.

PMID- 16440964
TI  - Self assessment exercises in emergency medicine. Question 1. Septic arthritis.

PMID- 16440965
TI  - General practice.

PMID- 16440966
TI  - Jean Dominique, First Baron Larrey.

PMID- 16440967
TI  - Can nurses halt primary care shake-up plans?

PMID- 16440968
TI  - Hospitals should be first to ban smoking.

PMID- 16440969
TI  - Understanding chronic fatigue.

PMID- 16440970
TI  - Keeping it natural.

PMID- 16440971
TI  - An overview of the new resuscitation guidelines.
AB  - New resuscitation guidelines contain significant changes intended to improve
      resuscitation practice and survival from cardiac arrest. The guidelines also
      include helpful new sections with guidance on in-hospital resuscitation. This
      article provides an overview of the key changes and discusses their practice
      implications for nurses.

PMID- 16440972
TI  - Leprosy.

PMID- 16440973
TI  - The liver. Part 6: Liver transplantation.
AB  - Advanced surgical techniques and the development of effective immunosuppressive
      therapies have enabled liver transplantation to be performed in any age group
      with a high graft and patient survival rate.

PMID- 16440974
TI  - The management of animal and human bite wounds.
AB  - Every year, large numbers of people are bitten by animals, and a smaller number
      by humans. The consequences can be serious. However, better health education to
      help prevent bites and teaching a bite-avoidance strategy when someone is being
      treated for a bite may help to reduce the problem. This article discusses
      treatment options and the possible complications of bite wounds.

PMID- 16440975
TI  - Smoking cessation and health inequality: an equity audit.
AB  - Nurses have a vital role in undertaking brief interventions and directing
      patients to NHS stop smoking services. This article reports on an audit that
      aimed to determine whether the local NHS stop smoking service delivered a 52-week
      quit rate in line with the national average of 15 per cent, and to relate this
      finding to health inequalities.

PMID- 16440976
TI  - Goserelin.

PMID- 16440977
TI  - Patient restraint positions in a psychiatric inpatient service.
AB  - AIM: The use of physical intervention on psychiatric inpatient units continues to
      be a source of debate and controversy. Some studies and national clinical
      guidelines have identified particular restraint positions as both dangerous and
      undesirable. The following study attempts to identify clinical variables that may
      make physical restraint in a particular position more likely. METHOD: A cross
      sectional survey design was adopted and data was obtained from a violence and
      aggression audit form used by the trust. This form has 122 items to be completed
      by staff within 72 hours of an episode of patient aggression or self-harm. Ten
      variables were selected for scrutiny on the basis of their potential clinical
      importance. RESULTS: The survey found that prone restraint was significantly
      associated with others reporting the patient's imminent violence and high
      intensity observation after the incident. Supine restraint was significantly
      associated with the patient being withdrawn and/or refusing to communicate prior
      to the episode and with a high severity incident rating after the incident.
      CONCLUSION: If we work on the premise that restraint in the prone position is
      less desirable than interventions undertaken with the patient in the supine
      position, this study clearly suggests that we have an opportunity to influence
      the nature of intervention through quite minimal changes to training programmes.
      It is important that any change in emphasis around intervention does not create a
      sense that controlled descent to the floor is inevitable. The principle of its
      use as a 'last resort in the event of loss of control on the feet' has to be
      maintained.

PMID- 16440978
TI  - Tackling bullying within a team.

PMID- 16440979
TI  - A fulfilling career with many options.

PMID- 16440980
TI  - Simple synthesis and anti-HIV activity of novel cyclopentene phosphonate
      nucleosides.
AB  - A very simple synthetic route for novel cyclopentene phosphonate nucleosides is
      described. The characteristic cyclopentene moiety 6 was constructed via a ring
      closing metathesis of divinyl 5, which could be readily prepared from
      diethylmalonate. The condensation of the mesylate 11 with nucleobases (A, C, T,
      U) under nucleophilic substitution conditions (K2CO3, 18-Crown-6, DMF) afforded
      the target nucleosides 12, 13, 14, and 15. In addition, the antiviral evaluations
      against various viruses were performed.

PMID- 16440981
TI  - Effects of a modified dye-labeled nucleotide spacer arm on incorporation by
      thermophilic DNA polymerases.
AB  - The ability of eight commercially available thermophilic DNA polymerases to
      sequentially incorporate fluorescently labeled nucleotides sequentially was
      analyzed by a gel based primer extension assay. Cy5-dUTP or a variant nucleotide
      in which the linker had been lengthened by 14 atoms between the dye and the
      nucleobase were compared. We found that the Cy5-dUTP with a longer linker
      resulted in longer primer extension lengths. Furthermore, some of the assayed
      polymerases are capable of extending the primer to the full or near full length
      of 30 nucleotides using dye-labeled nucleotides exclusively.

PMID- 16440982
TI  - Synthesis and antiviral screening of some thieno[2,3-d]pyrimidine nucleosides.
AB  - Some cyclic and acyclic nucleosides of thieno[2,3-d]-pyrimidine derivatives were
      synthesized via the reaction of compounds 1 and 2 or 3 and 4 with 2-chloroethyl
      methyl ether or 2,3,4, 6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide.
      Nucleosides 9, 10, 15, and 16 were tested as antiviral agents against herpes
      simplex virus type-1 (HSV-1) and hepatitis-A virus (HAV). Compound 15 showed the
      highest effect on HSV-1 than the other three compounds, while the four tested
      compounds did not show any activity against HAV.

PMID- 16440983
TI  - Efficient synthesis of [2-15N]guanosine and 2'-deoxy[2'-15N]guanosine derivatives
      using N-(tert-butyldimethylsilyl)[15N]phthalimide as a 15N-labeling reagent.
AB  - Nucleophilic aromatic substitution of 9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)
      6-chloro-2-fluoro-9H-purine with N-(tert-butyldimethylsilyl) [15N]phthalimide in
      the presence of a catalytic amount of CsF at room temperature in DMF efficiently
      afforded the 6-chloro-2-[15N]phthalimidopurine derivative, which was subsequently
      converted to the [2-15N]guanosine derivative. The 2'-deoxy[2'-15N]guanosine
      derivative was also efficiently synthesized through a similar procedure.

PMID- 16440984
TI  - New AZT conjugates as potent anti-HIV agents.
AB  - In an attempt to discover anti-HIV agents with much reduced cytotoxicity from the
      currently available HIV-reverse transcriptase inhibitors, AZT conjugates of
      cholanic acids, 2-imidazolidone-4-carboxylic acid and its derivatives, and N,N'
      disubstituted 5-hydroxy-tetrahydropyrimidin-2-ones have been synthesized and
      their anti-HIV profiles determined with CEM-SS cell line. The AZT conjugates with
      2-imidazolidone-4-carboxylic acid and 2-pyrrolidone-5-carboxylic acid through an
      ester linkage, and with N,N'-diphenyl-5-hydroxy-tetrahydropyrimidin-2-one through
      a succinate tether showed significantly higher therapeutic indexes than AZT while
      they also retained or enhanced AZT's anti-HIV activity. Thus, structural features
      that favor the desired therapeutic profile of the conjugates appear to include a
      five-membered ring cyclic urea or lactam, and six-membered ring cyclic urea with
      N,N'-diphenyl substitution.

PMID- 16440986
TI  - Solid-phase synthesis of 5'-deoxy-5'-amino-clitocine analogues.
AB  - Several 6-substituted-amino-5'-deoxy-5'-amino-clitocine analogues were
      synthesized in a parallel fashion in solid phase. The desired scaffold was
      generated by coupling 2,3-O-bis-(t-butyldimethylsilyl)-5-N-(monomethoxytrityl
      polystyrene-resin)-1,5-diamino-5-deoxy-beta-D-ribofuranose and 4, 6-dichloro-5
      nitropyrimidine. The scaffold was then reacted with a variety of amines to
      generate a small library of 14 analogues of 5'-deoxy-5'-amino-clitocine following
      a protocol developed earlier.

PMID- 16440985
TI  - Acyclic pyrazolo[3,4-d]pyrimidine nucleoside as potential leishmaniostatic agent.
AB  - A new synthesis of 6-amino-1-hydroxyethoxymethyl-4 (5H)-oxopyrazolo[3, 4
      d]pyrimidine (4) has been mentioned. Compound 4 exhibited inhibition of
      amastigotes of Leishmania donovani to the extent of 89 % at 30 microg/mL, whereas
      iso-guanine analogue 5 had the inhibition only to the extent of 52.8% at 100
      microg/mL in vitro. In hamster model the maximum inhibitory response for compound
      4 against amastigotes multiplication was observed to be 94% at 50 mg/kg single
      dose for 5 consecutive days.

PMID- 16440987
TI  - Complexing properties of some pyrimidines.
AB  - The synthesis of transition metal barbiturate, and thiobarbiturate complexes
      containing different functional groups of variable electronic character with
      CoII, NiII, CuII, PdII, and PtII have been prepared. The stereochemistry and the
      mode of bonding of the complexes were determined by elemental analysis and
      electronic and vibrational spectra together with their magnetic moment values.
      Electronic spin resonance of copper complexes were recorded. The Racah parameter
      of some cobalt and nickel complexes were calculated. Some of the complexes are of
      mixed stereochemistry. All the PdII or PtII complexes are of square planar
      geometries.

PMID- 16440988
TI  - Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M
      associated HIV-1 drug resistance towards emtricitabine and lamivudine.
AB  - Emtricitabine (FTC) and lamivudine (3TC) are deoxycytidine analogues with potent
      and selective inhibition of human immunodeficiency virus (HIV) and hepatitis B
      virus (HBV) replication. The K65R mutation in the HIV reverse transcriptase (RT)
      confers reduced susceptibility to 3TC, ddC, ddI, abacavir, and tenofovir in
      vitro. The Q151M mutation confers reduced susceptibility to many of the approved
      anti-HIV nucleoside analogues with the exception of 3TC and tenofovir. The double
      mutation K65R/Q151M has been shown to be more resistant to many NRTIs than either
      of the single mutations alone. In this study, we measured the antiviral activity
      of FTC and 3TC against HIV-1 containing K65R, Q151M, and K65R/Q151M mutations. We
      also studied the steady-state kinetic properties for the inhibition of dCTP
      incorporation by FTC 5'-triphosphate (TP) and 3TC-TP In addition, we measured the
      incorporation of dCTP, FTC-TP, and 3TC-TP into a random sequence DNA/DNA
      primer/template by the HIV-1 RTs using pre-steady-state kinetic analysis.
      Finally, we studied the incorporation of these deoxycytidine analogues into a HIV
      1 genomic DNA/DNA primer/template by K65R HIV-1 RT to address certain concerns
      associated with DNA sequence specificity. Overall, this study demonstrated that
      K65R and K65R/Q151M related drug resistance to FTC and 3TC was mainly due to a
      significant decrease in the rate of incorporation. There was little to no effect
      on the binding affinities of the mutant HIV-1 RTs for the deoxycytidine
      analogues. The Q151M mutation remained sensitive to both FTC and 3TC in both cell
      culture and enzymatic assays. At a molecular level, FTC-TP was incorporated at
      least as efficiently as 3TC-TP for all of the HIV-1 RT and primer/templates
      tested.

PMID- 16440993
TI  - Amiodarone-induced toxicity hits close to home.

PMID- 16440989
TI  - Synthesis and antiviral evaluation of novel 4'-hydroxymethyl branched apiosyl
      nucleosides.
AB  - Novel 4'-hydroxymethyl branched apiosyl nucleosides were synthesized in this
      study. The introduction of a hydroxymethyl group in the 4'-position was
      accomplished by a [3,3]-sigmatropic rearrangement. Apiosyl sugar moiety was
      constructed by sequential ozonolysis and reductions. The natural bases (uracil,
      thymine, cytosine, and adenine) were efficiently coupled by a classical glycosyl
      condensation procedure (persilyated base and TMSOTf). The antiviral activities of
      the synthesized compounds were evaluated against HIV-1, HSV-1, HSV-2, and HCMV.
      Compound 18 displayed moderate anti-HCMV activity (EC50 = 20.1 microg/mL) without
      exhibiting any cytotoxicity up to 100 microM.

PMID- 16440996
TI  - A reader remembers a patient with methemoglobinemia.

PMID- 16440999
TI  - Survey: nurses speak up about hospital pharmacists.

PMID- 16441003
TI  - You, too, can go to camp this summer.

PMID- 16441002
TI  - Kidney transplants in HIV patients?

PMID- 16441005
TI  - The delicate business of burn care.

PMID- 16441006
TI  - Patient information. How to care for your burn wound.

PMID- 16441004
TI  - Brain monitors.

PMID- 16441007
TI  - Pay attention to patient positioning!

PMID- 16441008
TI  - You can live the lifestyle you teach.

PMID- 16441009
TI  - Thank God I went to work today!

PMID- 16441010
TI  - Water-vapor isotope ratio measurements in air with a quantum-cascade laser
      spectrometer.
AB  - A spectrometer was used in the laboratory to study water-vapor isotope ratio
      measurements in air: H2 18O/H2 16O and HDO/H2 16O near 6.7 microm. The spectral
      region ranging from 1483 to 1487 cm(-1), which is suitable for the in situ laser
      sensing of major water-vapor isotopologues in the middle atmosphere from airborne
      or balloonborne platforms, was investigated by use of a continuous-wave
      distributed feedback quantum-cascade laser. The concentrations obtained were
      compared with the concentrations obtained with a hygrometer. The sigma(18O)
      values were found to be in excellent agreement with the standard value for two
      individual lines. The sigma(D) value was slightly higher than the standard value.

PMID- 16441011
TI  - Polarization of completely coherent random electromagnetic beams.
AB  - It is shown that the spectral degree of polarization rho(r, omega) of a
      fluctuating electromagnetic beam which is completely coherent throughout a domain
      D is necessarily the same at every point in D. It can take on any value in the
      range 0 < or = rho < or = 1. In particular, the fully coherent beam can be
      completely polarized or completely unpolarized throughout D.

PMID- 16441012
TI  - Generation of a hollow dark spherical spot by 4pi focusing of a radially
      polarized Laguerre-Gaussian beam.
AB  - The properties of the focal spot for 4pi focusing with radially polarized first
      order Laguerre-Gaussian beams are calculated. It is shown that a focal spot that
      has an extremely sharp dark region at the center and an almost-perfect spherical
      symmetry can be achieved. When such a hollow dark spherical spot is used in 4pi
      fluorescence depletion microscopy, an axial FWHM spot size of approximately 39 nm
      and a transverse FWHM spot size of approximately 64 nm can be achieved
      simultaneously in a practical system.

PMID- 16441013
TI  - Method of making mosaic gratings by using a two-color heterodyne interferometer
      containing a reference grating.
AB  - We propose and demonstrate a two-color heterodyne interferometric method for
      making a perfect mosaic of two planar gratings that can substitute for a single
      and larger grating without introducing wavefront aberration at any wavelength.
      The lateral and longitudinal phase errors are separated and eliminated by use of
      two wavelengths in the interferometry. The accuracy of the phase difference
      measurement is improved by this heterodyne scheme. The method ensures that the
      lateral gap between the two subaperture gratings is an integer multiple of the
      grating period. For a pair of 0.72 microm period gratings we experimentally
      achieved a lateral alignment error of less than 1% of the grating period.

PMID- 16441014
TI  - Diffraction grating eigenvector for translational and rotational motion.
AB  - Future energy scaling of high-energy chirped-pulse amplification systems will
      benefit from the capability to coherently tile diffraction gratings into larger
      apertures. Design and operation of a novel, accurate alignment diagnostic for
      coherently tiled diffraction gratings is required for successful implementation
      of this technique. An invariant diffraction direction and phase for special moves
      of a diffraction grating is discussed, allowing simplification in the design of
      the coherently tiled grating diagnostic. An analytical proof of the existence of
      a unique diffraction grating eigenvector for translational and rotational motion
      that conserves the diffraction direction and diffracted wave phase is presented.

PMID- 16441015
TI  - Beam cleanup in a self-aligned gradient-index Brillouin cavity for high-power
      multimode fiber amplifiers.
AB  - We propose a beam cleanup setup to convert a multimode beam into a single-mode
      beam by use of the Brillouin effect in a multimode gradient-index (GI) fiber.
      Phase conjugation and beam cleanup regimes in highly multimode fibers are
      discussed, and the self-aligned GI fiber Brillouin cavity is presented. We report
      a preliminary conversion from an M2=6.5 beam into an M2=1.3 beam with 31%
      efficiency.

PMID- 16441016
TI  - Suppression of stimulated Brillouin scattering in high-power single-frequency
      fiber amplifiers.
AB  - The effect of temperature variation along a high-power fiber amplifier on the
      stimulated Brillouin scattering (SBS) threshold is considered theoretically. We
      show that for an end-pumped rare-earth-doped double-clad fiber the inhomogeneous
      distribution of temperature, which is caused by the absorption of pump radiation,
      may result in total suppression of SBS even for output powers well above 200 W.

PMID- 16441017
TI  - Defect and lattice structure for air-silica index-guiding holey fibers.
AB  - We propose new design parameters for index-guiding holey fiber that can provide
      flexibility in defect and lattice design and adiabatic mode transformation
      capability. The new defect consists of a central air hole and a germanosilicate
      ring surrounding it, which results in a large-area annulus mode profile, low
      splice losses to standard fiber, 0.7 dB at 1.55 microm, and chromatic dispersion
      with a low slope, 0.002 ps/km nm2.

PMID- 16441018
TI  - Ytterbium gain band self-induced modulation instability laser.
AB  - We demonstrate an ytterbium gain band self-induced modulation instability laser.
      A highly nonlinear holey fiber is used to provide the anomalous dispersion
      required for bright soliton generation at 1 microm. The all-fiber integrated
      source yields a 40 GHz train of 4 ps pulses at a wavelength of 1064 nm.

PMID- 16441019
TI  - Characterization of a fiber lens.
AB  - A practical method for characterizing microstructure fiber lenses in the near
      field is described. By detecting the optical power of the light reflected by a
      mirror and coupled back into the single-mode fiber, one can accurately determine
      the focal point and the working distance of a fiber lens. The approach is
      relatively simple and easy to implement. The accuracy in determining the focal
      point and working distance is better than 2%.

PMID- 16441020
TI  - Hollow-core microstructured polymer optical fiber.
AB  - We have fabricated microstructured polymer optical fibers that guide light in a
      hollow core using the photonic bandgap mechanism. The hollow core allows the use
      of polymer fibers to be extended to wavelength ranges where material absorption
      typically prohibits their use, with attenuation lower than the material loss
      observed in the infrared. The fabrication method is similar to other
      microstructured polymer optical fibers, which has favorable implications for the
      feasibility of manufacturing such bandgap fibers.

PMID- 16441021
TI  - Homodyne detection readout for bit-oriented holographic memories.
AB  - Homodyne detection is proposed to increase the readout signal of bit-oriented
      holographic memories. It can be easily implemented on present memory
      architectures by making the diffracted signal interfere with a reflection of the
      reading beam. The large resulting increase of the readout signal can be used to
      enhance the data transfer rate. A first experimental demonstration of such a
      readout procedure is presented.

PMID- 16441022
TI  - Cell refractive index tomography by digital holographic microscopy.
AB  - For what we believe to be the first time, digital holographic microscopy is
      applied to perform optical diffraction tomography of a pollen grain. Transmission
      phase images with nanometric axial accuracy are numerically reconstructed from
      holograms acquired for different orientations of the rotating sample; then the
      three-dimensional refractive index spatial distribution is computed by inverse
      radon transform. A precision of 0.01 for the refractive index estimation and a
      spatial resolution in the micrometer range are demonstrated.

PMID- 16441023
TI  - Depth from diffracted rotation.
AB  - The accuracy of depth estimation based on defocus effects has been essentially
      limited by the depth of field of the imaging system. We show that depth
      estimation can be improved significantly relative to classical methods by
      exploiting three-dimensional diffraction effects. We formulate the problem by
      using information theory analysis and present, to the best of our knowledge, a
      new paradigm for depth estimation based on spatially rotating point-spread
      functions (PSFs). Such PSFs are fundamentally more sensitive to defocus thanks to
      their first-order axial variation. Our system acquires a frame by using a
      rotating PSF and jointly processes it with an image acquired by using a standard
      PSF to recover depth information. Analytical, numerical, and experimental
      evidence suggest that the approach is suitable for applications such as
      microscopy and machine vision.

PMID- 16441024
TI  - Coherence function analysis of the higher-order aberrations of the human eye.
AB  - We measured the wavefront aberrations of the eyes of five subjects with a Shack
      Hartmann sensor sampling at 21.2 Hz and decomposed the measurements into Zernike
      aberration terms up to and including the fifth radial order. Coherence function
      analysis was used to determine the common frequency components between the
      aberrations within subjects. We found the results to be highly subject dependent.
      The coherence values were typically <0.4. Possible reasons for this are
      discussed. Coherence function analysis is a useful tool that can be used in
      future investigations to determine correlations between the aberration dynamics
      of the eye and other physiological mechanisms.

PMID- 16441025
TI  - Direct determination of the refractive index and thickness of a biolayer based on
      coupled waveguide-surface plasmon resonance mode.
AB  - A coupled waveguide-surface plasmon resonance (CWSPR) biosensor based on the
      Kretschmann configuration is developed. The CWSPR couples the surface plasmon
      resonance (SPR) mode and the waveguide mode and generates two sharp resonance
      dips in the reflectivity spectrum. The proposed biosensor not only retains the
      same sensing sensitivity as that of a conventional SPR device but also yields
      sharper dips in the reflectivity spectrum and therefore provides an improved
      measurement precision. The two reflectivity spectrum dips enable the refractive
      indices and thicknesses of both the self-assembled monolayer and a layer of human
      serum albumin absorbed dynamically on the sensing surface to be determined
      directly on a real-time basis. The CWSPR biosensor provides the capability to
      detect the biomolecular conformational changes that occur in biomolecular kinetic
      interactions.

PMID- 16441026
TI  - Correlation of static speckle with sample properties in optical coherence
      tomography.
AB  - We present theoretical calculations, based on a random phasor sum model, which
      show that the optical coherence tomography speckle contrast ratio is dependent on
      the local density of scattering particles in a sample, provided that the
      effective number of scatterers in the probed volume is less than about five. We
      confirm these theoretical predictions experimentally, using suspensions of
      microspheres in water. The observed contrast ratios vary in value from the
      Rayleigh limit of 0.52 to in excess of 2, suggesting that the contrast ratio
      could be useful in optical coherence tomography, particularly when imaging in
      ultrahigh-resolution regimes.

PMID- 16441027
TI  - Plane-wave fluorescence tomography with adaptive finite elements.
AB  - We present three-dimensional fluorescence yield tomography of a tissue phantom in
      a noncontact reflectance imaging setup. The method employs planar illumination
      with modulated light and frequency domain fluorescence measurements made on the
      illumination plane. An adaptive finite-element algorithm is used to handle the
      ill-posed and computationally demanding inverse image reconstruction problem.
      Tomographic images of fluorescent targets buried at 1-2 cm depths from the
      illumination surface demonstrate the feasibility of fluorescence tomography from
      reflectance tomography in clinically relevant tissue volumes.

PMID- 16441028
TI  - Superenhanced backscattering of light by nanoparticles.
AB  - We report a physical explanation for the phenomenon wherein the backscattering of
      light by dielectric particles of sizes between 100 and 1 nm is enhanced by 7-11
      orders of magnitude. The phenomenon involves complex composite interactions
      between a dielectric microsphere and a nanoparticle positioned in close proximity
      to the microsphere. We provide both analytical and perturbation analyses that
      show that the enhanced backscattering intensity of a nanoparticle is proportional
      to the third power of its size parameter. Potential applications of this
      phenomenon include visible-light detection, characterization, and manipulation of
      particles as small as a few nanometers.

PMID- 16441029
TI  - Automatic alignment of a Kirkpatrick-Baez active optic by use of a soft-x-ray
      Hartmann wavefront sensor.
AB  - We present what we believe to be the first automatic alignment of a synchrotron
      beamline by the Hartmann technique. Experiments were performed, in the soft-x-ray
      range (E=3 keV, lambda=0.414 nm), by using a four-actuator Kirkpatrick-Baez (KB)
      active optic. A system imaging the KB focal spot and a soft-x-ray Hartmann
      wavefront sensor were used alternatively to control the KB optic. The beam
      corrected with the help of the imaging system was used to calibrate the wavefront
      sensor. With both closed loops, we focused the beam into a 6.8 microm x 9 microm
      FWHM focal spot.

PMID- 16441030
TI  - Phase-locked, low-noise, frequency agile titanium:sapphire lasers for
      simultaneous atom interferometers.
AB  - We demonstrate a laser system consisting of a >1.6 W titanium:sapphire laser that
      is phase locked to another free-running titanium:sapphire laser at a wavelength
      of 852 nm with a phase noise of -138 dBc/Hz at 1 MHz from the carrier, using an
      intracavity electro-optic phase modulator. The residual phase variance is 2.5 x
      10(-8) rad2 integrated from 1 Hz to 10 kHz. This system can phase-continuously
      change the offset frequency within 200 ns with frequency steps up to 4 MHz.
      Simultaneous atom interferometers can make full use of this ultralow phase noise
      in differential measurements, where influences from the vibration of optics are
      greatly suppressed in common mode.

PMID- 16441031
TI  - Index-of-refraction sensors: virtually unlimited sensing power at the critical
      angle.
AB  - In an effort to improve and simplify refractive index sensors, we identified a
      basic operation mode at the critical angle. Sensitivity to the refractive index
      is higher than in standard surface plasmon resonance sensors, and we have been
      able to demonstrate analytically that it is virtually an unbounded value. We
      describe this approach and submit a complete analytical study demonstrating its
      unlimited sensing power. To test the approach, we constructed an economical and
      basic sensor. Despite its simplicity, we demonstrated the discrimination
      capability to be of the order of 10(-6), as far as we know close to the best
      sensitivity ever recorded. This detection method is generally applicable to any
      optical system and may pave the way for the next generation of optical sensing
      devices.

PMID- 16441032
TI  - Femtosecond laser microprocessing with three-dimensionally isotropic spatial
      resolution using crossed-beam irradiation.
AB  - We describe the use of a crossed-beam irradiation system in three-dimensional
      femtosecond laser microprocessing to obtain three-dimensionally isotropic spatial
      resolution. In the crossed-beam geometry, two orthogonal objective lenses are
      arranged to share a common focal point. The synthesized focal spot produces an
      isotropic illumination volume. We demonstrate that microfluidic channels with
      substantially circular cross-sectional shapes can be directly fabricated inside
      glass by using the crossed-beam irradiation system.

PMID- 16441033
TI  - Integrated wavelength stabilization of in-plane semiconductor lasers by use of a
      dual-grating reflector.
AB  - We summarize a novel integrated wavelength-stabilization scheme for broad stripe
      surface-emitting lasers. The method is based on two gratings fabricated on
      opposite sides of a device in which the first grating disperses light through the
      substrate to the opposite side, where the second surface has a feedback grating
      that operates under total internal reflection and in the Littrow condition to
      provide feedback into the gain medium. Experimental results have been obtained
      for both high power and a narrow linewidth, showing a CW slope of 0.85 W/A.

PMID- 16441034
TI  - Diode-pumped passively mode-locked Nd:YVO4 laser at 914 nm.
AB  - We demonstrate, for the first time, to our knowledge, a diode-pumped passively
      mode-locked Nd:YVO4 laser, operating on the 4F(3/2)-4I(9/2) transition of the
      neodymium ion at 914 nm. We obtained 8.8 ps pulses at approximately 914 nm at a
      repetition rate of 94 MHz, and an averaged output power of 87 mW by using a
      semiconductor saturable absorber mirror.

PMID- 16441035
TI  - Adaptive control of laser modal properties.
AB  - An adaptive optical system for precise control of a laser beam's mode structure
      has been developed. The system uses a dynamic lens based on controlled optical
      path deformation in a dichroic optical element that is heated with an auxiliary
      laser. Our method is essentially aberration free, has high dynamic range, and can
      be implemented with high average power laser beams where other adaptive optics
      methods fail. A quantitative model agrees well with our experimental data and
      demonstrates the potential of our method as a mode-matching and beam-shaping
      element for future large-scale gravitational wave detectors.

PMID- 16441036
TI  - Generation of mid-infrared radiation by self-difference frequency mixing in
      chromium-doped zinc selenide.
AB  - We report what we believe to be the first demonstration of mid-infrared
      generation (approximately 9 microm) by self-difference frequency generation in
      Fresnel birefringence quasi-phase-matched Cr:ZnSe laser slabs.

PMID- 16441037
TI  - 250 mW, 1.5 microm monolithic passively mode-locked slab-coupled optical
      waveguide laser.
AB  - We report the demonstration of a 1.5 microm InGaAsP mode-locked slab-coupled
      optical waveguide laser (SCOWL) producing 10 ps pulses with energies of 58 pJ and
      average output powers of 250 mW at a repetition rate of 4.29 GHz. To the best of
      our knowledge, this is the first passively mode-locked slab-coupled optical
      waveguide laser. The large mode and low confinement factor of the SCOWL
      architecture allows the realization of monolithic mode-locked lasers with high
      output power and pulse energy. The laser output is nearly diffraction limited
      with M2 values less than 1.2 in both directions.

PMID- 16441038
TI  - Efficient single-mode operation of a cladding-pumped ytterbium-doped helical-core
      fiber laser.
AB  - A novel approach to achieving robust single-spatial-mode operation of cladding
      pumped fiber lasers with multimode cores is reported. The approach is based on
      the use of a fiber geometry in which the core has a helical trajectory within the
      inner cladding to suppress laser oscillation on higher-order modes. In a
      preliminary proof-of-principle study, efficient single-mode operation of a
      cladding-pumped ytterbium-doped helical-core fiber laser with a 30 microm
      diameter core and a numerical aperture of 0.087 has been demonstrated. The laser
      yielded 60.4 W of output at 1043 nm in a beam with M2 < 1.4 for 92.6 W launched
      pump power from a diode stack at 976 nm. The slope efficiency at pump powers well
      above threshold was approximately 84%, which compares favorably with the slope
      efficiencies achievable with conventional straight-core Yb-doped double-clad
      fiber lasers.

PMID- 16441039
TI  - Solid-state laser spectral narrowing using a volumetric photothermal refractive
      Bragg grating cavity mirror.
AB  - Dramatic spectral narrowing of two normally broadband lasers, Ti:sapphire and
      Cr:LiSAF, was achieved by simply replacing the output mirror with a reflective,
      volumetric Bragg grating recorded in photothermal refractive glass. The output
      power of each laser was unchanged from that obtained using dielectric coated
      output mirrors with the same output coupling as the Bragg grating while spectral
      brightness increased by 3 orders of magnitude.

PMID- 16441040
TI  - Electrically injected quantum-dot photonic crystal microcavity light sources.
AB  - The design, fabrication, and characterization of an electrically injected quantum
      dot photonic crystal microcavity light source are described. The optical gain in
      the GaAs/AlGaAs-based device is provided by self-organized InGaAs quantum dots
      with ground-state room-temperature emission at 1.1 microm. The carriers are
      injected directly into the photonic crystal microcavity, which contains
      approximately 50 dots, avoiding surface state recombination in the photonic
      crystal pattern. The spectral characteristics of a single-defect photonic crystal
      microcavity show a single 2 nm broad microcavity resonance. The output power is
      of the order of a few tens of nanowatts.

PMID- 16441041
TI  - Fast dynamic holographic recording based on conductive ionic metal-alkanoate
      liquid crystals and smectic glasses.
AB  - Recordings of dynamic holograms with microsecond relaxation times under the
      action of nanosecond laser pulses are obtained in composites on the base of a
      novel class of liquid crystals (LCs) in ionic metal-alkanoates. Holographic
      parameters and relaxation characteristics are measured for doped lyotropic ionic
      LC, for sandwichlike cells (consisting of a dye layer and a layer of the
      lyotropic ionic LC), and for colored ionic smectic glasses. The structure of the
      materials is investigated by use of the small-angle x-ray technique. The
      mechanism of resonance nonlinearity in photosensitive centers and mechanisms of
      the grating erasure connected with a charge transport in the ionic conductive LC
      matrix are discussed.

PMID- 16441042
TI  - Shaping soliton properties in Mathieu lattices.
AB  - We address basic properties and stability of two-dimensional solitons in photonic
      lattices induced by the nondiffracting Mathieu beams. Such lattices allow for
      smooth topological transformation of radially symmetric Bessel lattices into
      quasi-one-dimensional periodic ones. The transformation of lattice topology
      drastically affects the properties of ground-state and dipole-mode solitons,
      including their shape, stability, and transverse mobility.

PMID- 16441043
TI  - Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging.
AB  - We have achieved rapid nonlinear vibrational imaging free of nonresonant
      background with heterodyne coherent anti-Stokes Raman scattering (CARS)
      interferometric microscopy. This technique completely separates the real and
      imaginary responses of nonlinear susceptibility chi(3) and yields a signal that
      is linear in the concentration of vibrational modes. We show that heterodyne CARS
      microscopy permits the detection of weak vibrational resonances that are
      otherwise overshadowed by the strong interference of the nonresonant background.

PMID- 16441044
TI  - Cascaded-chi(2)-interaction-based frequency-resolved optical gating in a
      periodically poled LiNbO3 waveguide.
AB  - We demonstrate a novel frequency-resolved optical gating (FROG) configuration
      based on cascaded second-order nonlinear interactions. Its implementation in a
      2.6 cm long quasi-phase-matched LiNbO3 waveguide allowed high-quality retrieval
      of 2 ps to 80 fJ pulses at 1.56 microm.

PMID- 16441045
TI  - Observation of modulational instability in discrete media with self-defocusing
      nonlinearity.
AB  - We report what we believe is the first observation of modulation instability in
      the anomalous-diffraction regions of a photonic lattice. The experiments were
      carried out in a 1D waveguide array fabricated in a lithium niobate crystal
      displaying the photovoltaic self-defocusing nonlinearity, and our results are
      confirmed numerically by simulating the nonlinear beam propagation.

PMID- 16441046
TI  - Impedance matching in photonic crystal microcavities for second-harmonic
      generation.
AB  - By numerically integrating the three-dimensional Maxwell equations in the time
      domain with reference to a dispersive quadratically nonlinear material, we study
      second-harmonic generation in planar photonic crystal microresonators. The
      proposed scheme allows efficient coupling of the pump radiation to the defect
      resonant mode. The outcoupled generated second harmonic is maximized by impedance
      matching the photonic crystal cavity to the output waveguide.

PMID- 16441047
TI  - Broadband light generation by noncollinear parametric downconversion.
AB  - Broadband light generation is demonstrated by noncollinear spontaneous parametric
      downconversion with a cw pump laser. By use of a suitable noncollinear phase
      matching geometry and a tightly focused pump beam, downconverted signals that
      feature a bell-shaped spectral distribution with a bandwidth approaching 200 nm
      are obtained. As an application of the generated broadband light, submicrometer
      axial resolution in an optical coherence tomography scheme is demonstrated; a
      free-space resolution down to 0.8 microm was achieved.

PMID- 16441048
TI  - All-ultraviolet time-resolved coherent anti-Stokes Raman scattering.
AB  - We report all-UV coherent anti-Stokes Raman scattering (CARS) in calcite with 250
      280 nm pump, Stokes, probe, and anti-Stokes light. UV CARS efficiency is
      approximately 7x higher than for comparable scattering in the visible, 480-540
      nm. Time-resolved UV CARS reveals lengthening of the dephasing time of 1086 cm(
      1) CO3(2-) internal vibrations from 4 to 7 ps with increasing vibrational
      excitation, consistent with a phonon depletion model.

PMID- 16441049
TI  - Writing 40 nm marks by using a beaked metallic plate near-field optical probe.
AB  - We have developed a near-field optical probe that uses a triangular metallic
      plate with a three-dimensionally tapered apex as a light source for thermally
      assisted magnetic recording. Numerical analysis using a finite-element method
      shows that the size of the optical spot generated at the apex is 15 nm x 20 nm,
      and the efficiency (defined as the ratio between the power of the optical near
      field at the surface of the recording medium and that of the incident light) is
      15% when the incident light is focused by a lens with a numerical aperture of
      0.8. The metallic plate was fabricated on the surface of a quartz slider and used
      for writing marks on a phase change recording medium. The marks were observed
      with a scanning electron microscope, and we confirmed that marks with a diameter
      of 40 nm were successfully written on the medium.

PMID- 16441050
TI  - High-efficiency calculations for three-dimensional photonic crystal cavities.
AB  - A numerical method was developed by combining a plane-wave-based transfer matrix
      method and a robust rational function interpolation algorithm. The optical
      properties of three-dimensional photonic crystal cavities were extracted in a
      short computation time with high numerical accuracy.

PMID- 16441051
TI  - Terahertz achromatic quarter-wave plate.
AB  - Phase retarders usually present a strong frequency dependence. We discuss the
      design and characterization of a terahertz achromatic quarter-wave plate. This
      wave plate is made from six birefringent quartz plates precisely designed and
      stacked together. Phase retardation has been measured over the whole terahertz
      range by terahertz polarimetry. This achromatic wave plate demonstrates a huge
      frequency bandwidth (upsilonmax/upsilonmin approximately 7), and therefore can be
      applied to terahertz time domain spectroscopy and polarimetry.

PMID- 16441052
TI  - Detecting magnetically guided atoms with an optical cavity.
AB  - We show that a low-finesse cavity can be efficient for detecting neutral atoms.
      The low finesse can be compensated for by decreasing the mode waist of the
      cavity. We have used a near-concentric resonator with a beam waist of 12 microm
      and a finesse of only 1100 to detect magnetically guided Rb atoms with a
      detection sensitivity of 0.1 atom in the mode volume. For future experiments on
      single-atom detection and cavity QED applications, it should be beneficial to use
      miniaturized optical resonators integrated on atom chips.

PMID- 16441053
TI  - Room-temperature slow light with semiconductor quantum-dot devices.
AB  - We demonstrate room-temperature slow light that is electrically and optically
      controllable by using a quantum-dot (QD) semiconductor optical amplifier (SOA) at
      zero and low bias below the transparency current. The absorption spectrum of the
      QD SOA exhibits a spectral dip with a corresponding group-index dispersion and
      group delay owing to coherent population oscillation caused by the interaction of
      pump and probe laser light near resonance of the first heavy-hole-conduction
      state transition. At an optical pump power of approximately 0.3 mW inside the
      single-mode waveguide without current injection, a group-index change of 3.0 with
      a bandwidth of 2 GHz was measured. This group-index change can be controlled by
      injection of electrical current and by changing the optical pump power.

PMID- 16441054
TI  - Self-compression of millijoule pulses to 7.8 fs duration in a white-light
      filament.
AB  - We demonstrate a novel technique for pulse compression of few-millijoule pulses
      with shorter than 10 fs duration. Our technique relies on spectral broadening in
      a white-light filament generated in a noble gas. In this filament we observe self
      compression of 45 fs pulses down to below 8 fs duration without the need for any
      additional dispersion compensation. Using input pulses of 5 mJ, we generate
      compressed pulses with up to 3.8 mJ pulse energy. Therefore this method is much
      more efficient than previously demonstrated compression schemes. The generated
      peak powers of more than 100 GW at a kilohertz repetition rate open up a
      perspective for compression of few-cycle pulses with energies well beyond the
      capacity of hollow-fiber compressors.

PMID- 16441055
TI  - Improved stabilization of a 1.3 microm femtosecond optical frequency comb by use
      of a spectrally tailored continuum from a nonlinear fiber grating.
AB  - We report significant enhancement (+24 dB) of the optical beat note between a 657
      nm cw laser and the second-harmonic generation of the tailored continuum at 1314
      nm generated with a femtosecond Cr:forsterite laser and a nonlinear fiber Bragg
      grating. The same continuum is used to stabilize the carrier-envelope offset
      frequency of the Cr:forsterite femtosecond laser and permits improved optical
      stabilization of the frequency comb from 1.0 to 2.2 microm. Using a common
      optical reference at 657 nm, a relative fractional frequency instability of 2.0 x
      10(-15) is achieved between the repetition rates of Cr:forsterite and Ti:sapphire
      laser systems in 10 s averaging time. The fractional frequency offset between the
      optically stabilized frequency combs of the Cr:forsterite and Ti:sapphire lasers
      is +/-(0.024 +/- 6.1) x 10(-17).

PMID- 16441056
TI  - Reshaping of attosecond x-ray pulses in thin crystals.
AB  - A method for reshaping and control of the duration of attosecond x-ray pulses in
      thin crystals is proposed. The finite width of the reflection and transmission
      curves around the Bragg angle allows one to engineer Fabry-Perot-type filters for
      the generation of a large variety of attosecond pulse shapes. The method
      considered here can be used to manipulate attosecond pulses produced by high
      harmonic generation and also for shorter wavelengths for attosecond pulses from x
      ray free-electron lasers. X-ray pulses with controllable amplitude and phase may
      find useful applications in the newly emerging area of attosecond time-resolved
      spectroscopy.

PMID- 16441058
TI  - Briarane-type diterpenoids from the Okinawan soft coral Pachyclavularia violacea.
AB  - Four new briarane-type diterpenoids, pachyclavulides A (1), B (2), C (3), and D
      (4), were isolated from the Okinawan soft coral Pachyclavularia violacea. The
      structures of these compounds were elucidated on the basis of the results of
      spectroscopic analysis. The absolute configuration of pachyclavulide A (1) was
      determined by the X-ray crystallographic analysis of its p-bromobenzoyl ester.

PMID- 16441059
TI  - Isolation and structural modification of 7-deoxynarciclasine and 7-deoxy-trans
      dihydronarciclasine.
AB  - As an extension of structure-activity relationship studies of pancratistatin (1),
      various techniques were first evaluated for separating the mixtures of 7
      deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a) isolated from
      Hymenocallis littoralis. An efficient solution for that otherwise difficult
      separation then allowed the lactam carbonyl group of protected (4c and 5c)
      alcohols 2b and 3a to be reduced employing lithium aluminum hydride. Cleavage
      (TBAF followed by H2SO4) of the silyl ester/acetonide protected 6a gave amine 8.
      X-ray crystal structure determinations were employed to confirm the structures of
      3,4-acetonide-5-aza-6-deoxynarciclasine (6b), 5-aza-6-deoxynarciclasine (8a), and
      5-aza-6-deoxy-trans-dihydronarciclasine (9a, 9b). Against the murine P388
      lymphocytic leukemia and a panel of human cancer cell lines, the parent natural
      products, 7-deoxynarciclasine (2b) and 7-deoxy-trans-dihydronarciclasine (3a),
      were found to generally be more cancer cell growth inhibitory (GI50 0.1 to <0.01
      microg/mL) than the compounds with structural modifications such as amine 8 by a
      factor of 10 or more. The trans ring juncture of isocarbostyril 3a proved to be
      an important modification of narciclasine (2a) for improving cancer cell growth
      inhibition in this series.

PMID- 16441060
TI  - A common protein fold topology shared by flavonoid biosynthetic enzymes and
      therapeutic targets.
AB  - The relationship between a natural product's biosynthetic enzyme and its
      therapeutic target is unknown. The concept of protein fold topologies, as a
      determining factor in recognition, has been developed through molecular modeling
      techniques. We have shown that biosynthetic enzymes and the therapeutic targets
      of three classes of natural products that inhibit protein kinases share a common
      protein fold topology (PFT) and cavity recognition points despite having
      different fold type classifications. The clinical agent flavopiridol would have
      been identified by this new approach.

PMID- 16441061
TI  - Terpenoid indole alkaloids from Winchia calophylla.
AB  - Three new indole alkaloids, N(4)-demethyl-12-methoxyalstogustine (1), 17-carboxyl
      N(4)-methylechitamidine chloride (2), and 17-carboxyl-12-methoxy-N(4)
      methylechitamidine chloride (3), along with 15 known alkaloids, were isolated
      from the ethanolic extract of the stem bark of Winchia calophylla. The structures
      of 1-3 were elucidated on the basis of spectroscopic means and chemical methods.
      The determination of relative configurations at C-19 and C-20 for 1-3 was aided
      by 13C NMR spectroscopic data. The absolute configurations of alkaloids 1-3 were
      determined by direct comparison of their CD spectra with those of known
      alkaloids. All the alkaloids were tested in cytotoxic assays against P-388 and A
      549 tumor cell lines, and only two of them showed weak activity against the A-549
      cell line.

PMID- 16441062
TI  - Cycloviolacin H4, a hydrophobic cyclotide from Viola hederaceae.
AB  - Cycloviolacin H4, a new macrocyclic miniprotein comprising 30 amino acid
      residues, was isolated from the underground parts of the Australian native violet
      Viola hederaceae. Its sequence, cyclo-(CAESCVWIPCTVTALLGCSCSNNVCYNGIP), was
      determined by nanospray tandem mass spectrometry and quantitative amino acid
      analysis. A knotted disulfide arrangement, which was designated as a cyclic
      cystine knot motif and characteristic to all known cyclotides, is proposed for
      stabilizing the molecular structure and folding. The cyclotide is classified in
      the bracelet subfamily of cyclotides due to the absence of a cis-Pro peptide bond
      in the circular peptide backbone. A model of its three-dimensional structure was
      derived based on the template of the homologous cyclotide vhr1 (Trabi et al.
      Plant Cell 2004, 16, 2204-2216). Cycloviolacin H4 exhibits the most potent
      hemolytic activity in cyclotides reported so far, and this activity correlates
      with the size of a surface-exposed hydrophobic patch. This work has thus provided
      insight into the factors that modulate the cytotoxic properties of cyclotides.

PMID- 16441063
TI  - Dioxapyrrolomycin biosynthesis in Streptomyces fumanus.
AB  - Streptomyces fumanus, intramurally coded as culture LL-F42248, produces a series
      of pyrrolomycins including dioxapyrrolomycin (1) as the principal component. Our
      biosynthetic studies revealed that feeding labeled acetate to growing cultures of
      S. fumanus yielded pyrrolomycins labeled in the phenyl ring only. When l-[methyl
      13C]methionine was fed, the labeled carbon atom was found in the methoxy group of
      pyrrolomycins H-J and in the methylenedioxy bridge of dioxapyrrolomycin. A
      Na15NO3-enriched medium was employed to produce 15N-labeled pyrrolomycins in
      which both nitrogen atoms were highly enriched, whereas feeding of 15N-labeled l
      proline furnished pyrrolomycins labeled in the pyrrole moiety. Thus, S. fumanus
      elaborates the pyrrolomycin skeleton from proline and a polyketide precursor.
      Since the organism readily converted 13C- or 15N-labeled pyrrolomycin C, G, or H
      into the correspondingly labeled dioxapyrrolomycin, these minor pyrrolomycins are
      actually precursors of the ultimate product, dioxapyrrolomycin.

PMID- 16441064
TI  - Glucosides from MBOA and BOA detoxification by Zea mays and Portulaca oleracea.
AB  - Incubation of Zea mays cv. Nicco seedlings with 6-methoxybenzoxazolin-2(3H)-one
      (MBOA) led to a minor detoxification product hitherto only found in Poaceae. This
      new compound was identified as 1-(2-hydroxy-4-methoxyphenylamino)-1-deoxy-beta
      glucoside 1,2-carbamate (1) (methoxy glucoside carbamate) and represents an
      analogue to the previously described 1-(2-hydroxyphenylamino)-1-deoxy-beta
      glucoside 1,2-carbamate (glucoside carbamate) from benzoxazolin-2(3H)-one (BOA).
      In Portulaca oleracea var. sativa cv. Gelber treatment with BOA resulted in
      further unknown detoxification products, which were not synthesized in detectable
      amounts after BOA absorption in all other species tested. Compound 1 easily
      undergoes decay into BOA-5-O-glucoside (2). Z. mays seedlings, known to produce
      BOA-6-O-Glc on incubation with BOA, are able to transform BOA-5-OH into BOA-5-O
      glucoside (2). Besides the known compounds, maize contained a formerly unseen
      product that accumulated during late stages of the detoxification process. It was
      isolated and identified as 1-(2-hydroxyphenylamino)-6-O-malonyl-1-deoxy-beta
      glucoside 1,2-carbamate (3) (malonyl glucoside carbamate).

PMID- 16441065
TI  - Chalcones and other compounds from the exudates of Angelica keiskei and their
      cancer chemopreventive effects.
AB  - Three new chalcones, xanthoangelol I (1), xanthoangelol J (2), and
      deoxydihydroxanthoangelol H (3), were isolated from an ethyl acetate-soluble
      fraction of exudates of the stems of Angelica keiskei, and their structures were
      established on the basis of spectroscopic methods. Nine aromatic compounds of
      known structure, 4-12, and a diacetylene, 13, were also isolated and identified
      from this same fraction. On evaluation of these compounds for their inhibitory
      effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in Raji cells, 1, 2, 4, and 9-12 showed
      potent inhibitory effects on EBV-EA induction. In addition, upon evaluation of
      the inhibitory effects against activation of (+/-)-(E)-methyl-2[(E)-hydroxyimino]
      5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, six compounds,
      namely, 1, 2, 4, 9, 11, and 12, exhibited potent inhibitory effects. Further,
      isobavachalcone (4) exhibited inhibitory effects on skin tumor promotion in an in
      vivo two-stage mouse skin carcinogenesis test using 7,12
      dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

PMID- 16441066
TI  - Isoflavonoids and other compounds from Psorothamnus arborescens with
      antiprotozoal activities.
AB  - Bioactivity-guided fractionation of the root extract of Psorothamnus arborescens
      yielded the new isoflavone 5,7,3',4'-tetrahydroxy-2'-(3,3
      dimethylallyl)isoflavone (1a) and the new 2-arylbenzofuran 2-(2'-hydroxy-4',5'
      methylenedioxyphenyl)-6-methoxybenzofuran-3-carbaldehyde (2), together with seven
      known compounds, including three isoflavones, fremontin (3a), glycyrrhisoflavone
      (4a), and calycosin (5), two pterocarpans, maackiain (6) and 4-hydroxymaackiain
      (7), one triterpene, oleanolic acid (8), and one chalcone, isoliquiritigenin (9).
      In addition, the structure of the isoflavone fremontin was revised using
      spectroscopic and chemical methods and was assigned the new structure 3a. The
      isoflavone 1a and the chalcone 9 displayed leishmanicidal activity with IC50
      values of 13.0 and 20.7 microM, respectively, against Leishmania donovani axenic
      amastigotes. Calycosin (5) exhibited selective toxicity against Trypanosoma
      brucei brucei (IC50 12.7 microM) compared to L. donovani amastigotes and Vero
      cells (IC50 100 and 159 microM, respectively). These results prompted us to test
      a small group of structurally related isoflavones for their antitrypanosomal
      activities. Genistein and 7,3',4'-trihydroxyisoflavone displayed promising
      activity (IC50 values 4.2 and 7.1 microM, respectively) and selectivity (IC50
      versus Vero cells: 32.9 and 135 microM, respectively). These studies suggest that
      the isoflavone skeleton deserves further investigation as a template for novel
      antileishmanial and trypanocidal compounds.

PMID- 16441067
TI  - 14,15-secopregnane derivatives from the leaves of Solenostemma argel.
AB  - Five new 14,15-secopregnane derivatives, named argelosides K-O (1-5), have been
      isolated from Solenostemma argel leaves. Their structures were established by a
      detailed spectroscopic analysis. In particular, argeloside N (1) showed in the
      sugar portion an unusual 3-O-methyl-2,6-dideoxyhexopyranose unit characterized by
      the occurrence of a Delta3 double bond, and argeloside O (5) displayed an unusual
      moiety linked to position 3 probably derived by the oxidation of a 3-O-methyl-2,6
      dideoxyhexopyranose unit. The propensity of compounds 2, 3, and 5 and argeloside
      F (6) to inhibit TNF-alpha release by LPS-stimulated RAW 264.7 mouse cells was
      evaluated.

PMID- 16441068
TI  - Lignans from cell suspension cultures of Phyllanthus niruri, an Indonesian
      medicinal plant.
AB  - Cell suspension cultures of Phyllanthus niruri were used to study the lignan
      profiles and biosynthesis. Suspension cultures yielded two lignans: the new
      cubebin dimethyl ether (1) and urinatetralin (2), a new lignan from P. niruri,
      but reported earlier from P. urinaria. This is the first report of cell
      suspension cultures of P. niruri that successfully produce lignans. Feeding 0.5
      mM ferulic acid or 0.5 mM caffeic acid, being early precursors of lignan
      biosynthesis, resulted in an increase up to 0.7 mg g(-1) DW of 1 (control value
      0.1 mg g(-1) DW) and up to 0.3 mg g(-1) DW of 2 (control value 0.2 mg g(-1) DW).
      Comparison of the lignan profiles of cell suspensions, callus cultures, aerial
      plant parts, roots, and seeds showed significant differences.

PMID- 16441069
TI  - Anxiolytic effect of natural galphimines from Galphimia glauca and their chemical
      derivatives.
AB  - The anxiolytic effects of galphimine B (1), galphimine A (2), and galphimine E
      (3), natural nor-secofriedelanes isolated from Galphimia glauca, as well as
      derivatives obtained by acetylation (4), hydrogenation of the C-1/C-2 double bond
      (5), basic hydrolysis followed by hydrogenation of the C-1/C-2 double bond (6),
      and deacetylation (7) of galphimine E (3), were evaluated on ICR mice exposed to
      the elevated plus-maze test. This study also included the evaluation of a
      galphimines-rich fraction (GRF) with a known concentration of 1-3, obtained from
      the dry leaves of G. glauca. Intraperitoneal administration of 15 mg/kg of 1, 2,
      6, and GRF (1 h before testing) caused an anxiolytic-like effect in the animals,
      increasing significantly (p <0.001) the percentage of time of permanence and the
      number of crossings toward the open arms of the plus-maze. No activity was
      detected after administration of compounds 3, 4, 5, and 7. These results showed
      that GRF had activity similar to the most active pure galphimines (1 and 2) and
      that, like for the spasmolytic activity previously reported, the main determining
      factor responsible for the anxiolytic activity of the compounds was the presence
      of free hydroxyl groups at C-4, C-6, and C-7 and the presence of the double bond
      in the A ring.

PMID- 16441070
TI  - Lupeol long-chain fatty acid esters with antimalarial activity from Holarrhena
      floribunda.
AB  - An ethnopharmacological investigation was conducted among the Baka pygmies of Dja
      biosphere reserve (Cameroon) to collect information on the antimalarial plants
      used in their daily life. Holarrhena floribunda is one of those plants. Extracts
      of the stem barks of H. floribunda showed remarkable inhibitory activity against
      drug-resistant strains of Plasmodium falciparum at doses of 1.02-18.53 microg/mL
      when tested in vitro against two parasite clones designated as Indochina (W-2)
      and Sierra Leone (D-6). The aqueous extract was the most active against Indochina
      (W-2), with IC50 values of 1.02 microg/mL, while the ethanolic extract appeared
      to be the most active against Sierra Leone (D-6), with an IC50 of 4.33 microg/mL.
      The bioassay-guided fractionation of the neutral fraction of the crude extract
      led to the isolation of lupeol (1) and its three new long-chain fatty acid ester
      derivatives, namely, 3-O-(3'-hydroxyeicosanoyl)lupeol (2), 3-O-[(2'
      (tetracosyloxy)acetyl]lupeol (3), and 3-O-[(1' '-hydroxyoctadecyloxy)-2'
      hydroxypropanoyl]lupeol (4). These new compounds displayed some in vitro
      inhibition activity against the chloroquine-resistant strain FCR-3 isolated from
      Gambia and the chloroquine-sensitive standard strain 3D7. The hydroxy group of
      the fatty acid side chain appears to decrease the observed activity.

PMID- 16441071
TI  - 2-substituted furans from the roots of Polyalthia evecta.
AB  - Four new 2-substituted furans, 19-(2-furyl)nonadeca-5,7-diynoic acid (1), 19-(2
      furyl)nonadeca-5-ynoic acid (2), 1-(2-furyl)pentacosa-7,9-diyne (3), and ester 21
      (2-furyl)heneicosa-14,16-diyne-19-(2-furyl)nonadeca-5,7-diynoate (4) have been
      isolated from the roots of Polyalthia evecta. Their structures were established
      by spectroscopic techniques. Compounds 1 and 1a showed antiplasmodial activity.
      The acids 1 and 2 exhibited antiviral activity against Herpes simplex type 1. In
      addition, 5 also showed cytotoxicity against the NCI-H187 cell line.

PMID- 16441072
TI  - Glycolipids from sponges. Part 17. Clathrosides and isoclathrosides, unique
      glycolipids from the Caribbean sponge Agelas clathrodes.
AB  - Two families of unique glycolipids, clathrosides A-C (2a-4a) and isoclathrosides
      A-C (5a-7a) were isolated from the Caribbean sponge Agelas clathrodes.
      Clathrosides and isoclathrosides are glycosides of a very-long-chain alcohol
      derived from fatty acids, a new class of glycolipids that appears to be
      characteristic of marine sponges. The six compounds differ in configuration and
      in the branching of alkyl chains. Stereostructures of the clathrosides were
      determined by NMR and CD spectroscopy, mass spectrometry, and chemical
      degradation. Location of the methyl branch on the proper alkyl chain required an
      exceptional 1-D TOCSY experiment, in which coherence was transferred through as
      many as 13 vicinal couplings.

PMID- 16441073
TI  - Alkaloids from Daphniphyllum longeracemosum.
AB  - Four new Daphniphyllum alkaloids, daphnilongeranins A-D (1-4), along with four
      known ones, daphniphylline, longistylumphylline A, deoxyisocalyciphylline B, and
      daphnicyclidin D, were isolated from the leaves and stems of Daphniphyllum
      longeracemosum. Daphnilongeranin A (1) is the first seco-10,17
      longistylumphylline A type Daphniphyllum alkaloid, and daphnilongeranin B (2) is
      a new C-22 nor-Daphniphyllum alkaloid based on a new C21 skeleton. Their
      structures and stereochemistry were determined using spectroscopic data and
      chemical methods.

PMID- 16441074
TI  - Highly N-methylated linear peptides produced by an atypical sponge-derived
      Acremonium sp.
AB  - RHM1 (1) and RHM2 (2) are highly N-methylated linear octapeptides produced by an
      atypical strain of Acremonium sp., cultured from a marine sponge collected in
      Papua New Guinea. The known peptaibiotic efrapeptin G (3) was also isolated from
      this fungus. The planar structures of 1 and 2 were assigned based on 1D- and 2D
      NMR experiments and fragmentation patterns from ESIMS. The absolute configuration
      of 1 was determined via Marfey's method; the absolute configuration of 2 is
      proposed to be identical. Efrapeptin G (3) displayed potent cytotoxicity against
      murine cancer cell lines, while RHM1 (1) and RHM2 (2) showed weak cytotoxicity
      against murine cancer cell lines; efrapeptin G (3) and RHM1 (1) also demonstrated
      antibacterial activity.

PMID- 16441075
TI  - Abietane diterpene alkaloids from Salvia yunnanensis.
AB  - Nine new abietane diterpene alkaloids containing an oxazole ring, salviamines A-F
      (1-6) and isosalviamines C-E (7-9), together with 17 known abietane diterpenes,
      were isolated and characterized from the roots of Salvia yunnanensis. The
      structures of 1-9 were elucidated by interpretation of their spectroscopic data.

PMID- 16441076
TI  - Kutznerides 1-4, depsipeptides from the actinomycete Kutzneria sp. 744 inhabiting
      mycorrhizal roots of Picea abies seedlings.
AB  - Bioassay-guided fractionation of culture supernatants of the actinomycete
      Kutzneria sp. 744 resulted in the isolation of four new depsipeptides (1-4).
      Structure analysis revealed the general structure: cyclo[2-(1-methylcyclopropyl)
      D-glycine-(2S,3aR,8aS)-6,7-dichloro-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3
      b]indole-2-carboxylic acid-3-hydroxy-D-glutamic acid-O-methyl-L-serine-L
      piperazic acid-(S)-2-hydroxy-3,3-dimethylbutanoic acid]. The 3-hydroxy-d-glutamic
      acid was present as its threo-isomer in 1 and 2 and as its erythro-isomer in 3
      and 4. The piperazic acid was modified to its (R)-4-chloro analogue in 2 and to
      its C-5/N unsaturated analogue in 4. Compounds 1-4 displayed moderate spore
      germination inhibiting activity against several common root-rotting fungi.

PMID- 16441077
TI  - Cytotoxic pregnane steroids from the formosan soft coral Stereonephthya
      crystalliana.
AB  - Nine new steroids, stereonsteroids A-I (1-9), were isolated from the methylene
      chloride solubles of the Formosan soft coral Stereonephthya crystalliana
      Kukenthal. The structures were elucidated by extensive spectroscopic analysis,
      and their cytotoxicity against selected cancer cells was measured in vitro.

PMID- 16441078
TI  - Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis
      of salvinicins A and B and other chemical transformations of salvinorin A.
AB  - Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the
      widely available psychoactive plant Salvia divinorum and is the first example of
      a non-nitrogenous opioid receptor ligand. At present, there is little information
      available as to why this compound is selective for kappa opioid receptors. One
      approach to better understanding the mode of binding of 1 at kappa receptors is
      to systematically alter the structure of 1 and examine the effects on opioid
      receptor affinity and activity. Currently, there is a paucity of methods
      described for the preparation of analogues derived from 1. Here, we report the
      investigation of several chemical transformations of 1 isolated from S.
      divinorum. In particular, this work provides a semisynthesis of salvinicins A (2)
      and B (3) and has identified 10a as the first neoclerodane diterpene with delta
      opioid antagonist activity.

PMID- 16441079
TI  - Phaeofurans and sorbicillin analogues from a fungicolous Phaeoacremonium species
      (NRRL 32148).
AB  - Two new benzofuran-derived metabolites of polyketide origin called phaeofurans A
      and B (1 and 2), along with three sorbicillin analogues (3-5), have been obtained
      from a fungicolous isolate of the genus Phaeoacremonium (NRRL 32148). The
      structures were determined by analysis of MS and 2D NMR data. The antifungal
      effects of the extract were ascribed to the sorbicillin analogues.

PMID- 16441080
TI  - Bacterial biofilm inhibitors from Diospyros dendo.
AB  - One new (1) and four known (2-5) ursene triterpenes with potent inhibition of the
      formation of the bacterial biofilm Pseudomonas aeruginosa PA01 were obtained from
      Diospyros dendo using a high-throughput natural products chemistry procedure.
      These compounds were isolated as mass-limited samples. The miniaturization of the
      structure elucidation and dereplication was performed primarily utilizing a
      capillary-scale NMR probe.

PMID- 16441081
TI  - Antibacterial compounds from Glycyrrhiza uralensis.
AB  - From the roots of Glycyrrhiza uralensis, two new pterocarpenes, glycyrrhizol A
      (1) and glycyrrhizol B (2), along with four known isoflavonoids, 5-O
      methylglycryol (3), isoglycyrol (4), 6,8-diisoprenyl-5,7,4'-trihydroxyisoflavone
      (5), and gancaonin G (6), were isolated using a bioassay-guided fractionation
      method. The structures of the new compounds (1and 2) were elucidated by
      spectroscopic data interpretation. The known compounds (3-6) were identified by
      comparison of their spectroscopic data with reported values in the literature.
      Glycyrrhizol A (1) and 6,8-diisoprenyl-5,7,4'-trihydroxyisoflavone (5) exhibited
      potent antibacterial activity against Streptococcus mutans with minimum
      inhibitory concentrations of 1 and 2 microg/mL, respectively, while glycyrrhizol
      B (2) and gancaonin G (6) showed more moderate activity.

PMID- 16441082
TI  - Isolation and synthesis of 4-bromopyrrole-2-carboxyarginine and 4-bromopyrrole-2
      carboxy-N(epsilon)-lysine from the marine sponge Stylissa caribica.
AB  - Two new bromopyrrole alkaloids were isolated from the Caribbean sponge Stylissa
      caribica. The new natural products, 4-bromopyrrole-2-carboxyarginine (1) and 4
      bromopyrrole-2-carboxy-N(epsilon)-lysine (2), are derivatives of amino acids
      linked with a 4-bromopyrrole-2-carboxylic acid. The structures were elucidated on
      the basis of NMR and MS/MS data and their absolute configurations assigned via
      synthesis.

PMID- 16441083
TI  - Wortmannilactones A-D, 22-membered triene macrolides from Talaromyces wortmannii.
AB  - The fungus Talaromyces wortmannii, isolated from a soil sample collected in
      China's Yunnan province, produced four novel 22-membered macrolides, namely,
      wortmannilactones A-D (1-4). Structures 1-4 were elucidated by extensive 1D and
      2D NMR and MS spectral analyses. Compounds 1-4 exhibited in vitro cytotoxic
      activity against several human cancer cell lines with IC50 values ranging from
      28.7 to 130.5 microM.

PMID- 16441084
TI  - 5,6:8,9-diepoxy and other cytotoxic sterols from the marine sponge Homaxinella
      sp.
AB  - Four new (1, 2, 4, and 5) and 14 known (3 and 6-18) polyoxygenated sterols have
      been isolated from the MeOH extract of the marine sponge Homaxinella sp. by
      bioactivity-guided fractionation. The planar structures of the sterols were
      established by 1D and 2D NMR and MS spectroscopic analysis. 5,6:8,9-Diepoxy
      sterols (1-3) were isolated from a marine organism for the first time. The
      isolated sterols were tested against a panel of five human solid tumor cell lines
      and exhibited varying degrees of cytotoxicity.

PMID- 16441085
TI  - Cyclohaliclonamines A-E: dimeric, trimeric, tetrameric, pentameric, and hexameric
      3-alkyl pyridinium alkaloids from a marine sponge Haliclona sp.
AB  - A mixture of cyclohaliclonamines A-E (1-5), novel dimeric, trimeric, tetrameric,
      pentameric, and hexameric 3-alkylpyridinium alkaloids, was obtained from an
      Okinawan sponge Haliclona sp. Cyclohaliclonamines C-E are the first tetrameric,
      pentameric, and hexameric 3-alkylpyridinium alkaloids from natural sources. The
      structure determination of cyclohaliclonamines is discussed in detail.

PMID- 16441086
TI  - Isoflavonoids with antiestrogenic activity from Millettia pachycarpa.
AB  - Three new isoflavonoids, named millewanins G (1) and H (2) and furowanin B (3),
      were isolated from the leaves of Millettia pachycarpa. Their structures were
      elucidated on the basis of spectroscopic analyses. The antiestrogenic activity in
      the yeast two-hybrid assay of these isoflavonoids was examined and shown to be
      comparable with that of 4-hydroxytamoxifen.

PMID- 16441087
TI  - Lupane and oleanane triterpenoids from the cones of Liquidamber styraciflua.
AB  - A new lupane- (1) and a new oleanane-type (2) triterpenoid, together with a known
      compound, massagenic acid G, were isolated from the cones of Liquidamber
      styraciflua. The structures of 1 and 2 were determined as 6beta,30-dihydroxy-3
      oxolup-20(29)-en-28-oic acid and 3alpha-hydroxy-11-oxoolean-12-en-28-oic acid,
      respectively, on the basis of spectroscopic methods and chemical conversion.
      Compound 1 and several structural analogues were evaluated for cytotoxicity
      against the P388 (murine lymphocyte leukemia) and the A549 (human lung cancer)
      cell lines.

PMID- 16441089
TI  - Methanolysis products of disorazole A1.
AB  - Two new disorazole analogues were synthesized by acid-promoted methanolysis of
      disorazole A1 (1). Structural elucidation of both products (2 and 3), through 1D
      and 2D NMR experiments, verified that each resulted from epoxide cleavage. With
      antiproliferative activities in susceptible cell lines comparable to that of
      disorazole A1, these methanolysis products indicate that the C-9-C-10 epoxide is
      not an essential structural component for biological activity.

PMID- 16441088
TI  - A reassignment of (-)-mycothiazole and the isolation of a related diol.
AB  - A reinvestigation of the thiazole constituents from Cacospongia mycofijiensis,
      collected in Vanuatu, yielded known mycothiazole (3) plus a new derivative,
      mycothiazole-4,19-diol (6). The E stereochemistry at Delta14,15 of 3 has been
      revised to Z and the structural features of 6 are elucidated. These compounds,
      which presumably arise by the action of a polyketide-nonribosomal peptide
      synthetase (PKS/NRPS) hybrid, possess cytotoxic properties that need further
      exploration.

PMID- 16441090
TI  - An unusual oxalylated tetramic acid from the New Zealand basidiomycete Chamonixia
      pachydermis.
AB  - An unusual oxalylated tetramic acid, pachydermin (1), has been isolated from the
      New Zealand basidiomycete Chamonixiapachydermis. The full structure, which was
      not directly accessible by NMR methods, was deduced from that of a degradation
      product, 5-(3-chloro-4-hydroxybenzylidene)tetramic acid (2). The degradation
      product 2 exhibited mild antibacterial activity against Bacillus subtilis.

PMID- 16441091
TI  - Hurghadolide A and swinholide I, potent actin-microfilament disrupters from the
      Red Sea sponge Theonella swinhoei.
AB  - As part of our continuing interest in identifying anticancer drug leads from Red
      Sea marine organisms, we have investigated the sponge Theonella swinhoei. We
      report here the isolation and structure elucidation of swinholide A (1) and two
      new macrolides, swinholide I (2) and hurghadolide A (3). Swinholide I is the
      first derivative of swinholide A with hydroxylation at the side chain.
      Hurghadolide A possesses an unprecedented asymmetric 42-membered dilactone moiety
      and presents a novel skeleton of macrolides. The structural determinations were
      based on extensive interpretation of high-field NMR spectra and HRFABMS data.
      Swinholide I and hurghadolide A showed in vitro cytotoxicity against human colon
      adenocarcinoma (HCT-116) with IC50 values of 5.6 and 365 nM, respectively.
      Furthermore, swinholide I and hurghadolide A caused disruption of the actin
      cytoskeleton at concentrations of 70 and 7.3 nM, respectively. In addition, both
      compounds were active against Candida albicans.

PMID- 16441095
TI  - La9RbIr4O24: a rubidium-containing oxide with a new structure type.
AB  - Single crystals of La9RbIr4O24, grown from a molten rubidium hydroxide flux,
      crystallize in the space group I4/m with lattice parameters a = 7.7422(3) A and c
      = 17.7979(11) A. The oxide forms in a new complex structure type.

PMID- 16441092
TI  - From ergot to ansamycins-45 years in biosynthesis.
AB  - In this review the author traces his scientific career from its beginnings in
      Germany to his moves to, successively, Purdue University, The Ohio State
      University, and finally University of Washington. During this time his research
      progressed from extensive studies on ergot alkaloids, the stereochemistry of
      enzyme reactions, and tracer studies on antibiotic biosynthesis to its latest
      emphasis on the molecular biology of ansamycin antibiotics. The formative
      influence of several mentors and colleagues is acknowledged.

PMID- 16441096
TI  - Synthesis, characterization, and X-ray crystal structure of a gallium
      monohydroxide and a hetero-bimetallic gallium zirconium oxide.
AB  - A monomeric hydroxide of gallium, LGa(Me)OH, containing terminal hydroxide and
      methyl groups was prepared by the hydrolysis of LGa(Me)Cl in the presence of N
      heterocyclic carbene and water [L = HC{(CMe)(2,6-i-Pr2C6H3N)}2] in high yield and
      in a pure form. LGa(Me)OH was used as a synthon to assemble the first hetero
      bimetallic compound with a Ga-O-Zr core, [(LGaMe)(Cp2ZrMe)](mu-O).

PMID- 16441097
TI  - Exo-coordination-based supramolecular silver(I) complexes of S2O macrocycles:
      effect of ligand isomerism on the structural diversity.
AB  - An isomeric series of S2O macrocycles incorporating a xylyl group at the ortho
      (L1), meta (L2), and para (L3) positions were employed to examine the influence
      of the ring rigidity on silver(I) coordination modes in resulting supramolecular
      complexes (1-3); L1 and L3 afforded sandwich (1; Ag:L1 = 1:2) and infinite 1-D
      (3) complexes, respectively; otherwise, L2 gave the 1-D polymer (2a), 2:3 club
      sandwich (2b), and unique 2:4 bridged dinuclear complex (2c) complexes, in which
      their topologies vary with the solvent used.

PMID- 16441099
TI  - Relative energies of alpha and beta isomers of Keggin dodecatungstogallate.
AB  - The relative energies of beta Keggin heteropolytungstates, X(n+) W12O40(8-n)-,
      decrease as X(n+) is varied within period 3, from P5+ to Si4+ to Al3+. With
      heating of alpha-H5Ga3+ W12O40 at 200 degrees C in water, an equilibrated mixture
      of alpha (T(d); one 183W NMR signal) and beta (C(3v); three signals; 1:2:1 ratio)
      isomers is obtained. From deltaG(exp) = -RT ln K(beta-->alpha), in which (from
      71Ga NMR spectra) K(beta-->alpha) (= [alpha]/[beta]) = 5.0, beta-GaW12O40(5-) is
      0.65 kcal mol(-1) higher in energy than alpha-GaW12O40(5-). This finding is
      evaluated by analysis of the X-ray crystal structure alpha-K2Na3[GaW12O40] x 9.3
      H2O [trigonal, space group P3(2)21, a = 18.9201(13) A, b = 18.9201(13) A, c =
      12.5108(12) A, Z = 3, T = 100(2)K], comparison of the Shannon and Prewitt radii
      and Pauling electronegativities of Al3+ and Ga3+, and insight from density
      functional theory calculations, which predicted Ebeta - Ealpha = 0.32 kcal mol(
      1).

PMID- 16441098
TI  - Structural and electronic behavior of unprecedented five-coordinate iron(III) and
      gallium(III) complexes with a new phenol-rich electroactive ligand.
AB  - A new asymmetric pentadentate ligand was designed to impose low symmetry to
      trivalent ions. Five-coordinate Fe3+ and Ga3+ complexes were investigated by
      crystallographic, electrochemical, and electron paramagnetic resonance methods
      showing enhanced redox reversibility. Calculations were performed to account for
      the observed trends.

PMID- 16441100
TI  - Fe(III)-binding collagen mimetics.
AB  - The synthesis and characterization of hydroxamic acid containing single-chain and
      TRIS-assembled (where TRIS is tris(carboxyethoxymethyl)aminomethane) collagen
      mimetics are reported. We have engineered an Fe(III)-binding domain by placing a
      hydroxamic acid group at the C termini of collagen mimetic chains composed of the
      Gly-Pro-NLeu sequence. The circular dichroism spectra and thermal denaturation
      studies show an enhancement in triple-helical thermal stability upon the addition
      of Fe(III) for the TRIS-assembled structure. No triple-helical structure was
      detected for the single-chain collagen mimetic. From the absorbance shown in the
      UV-vis spectra, we believe that the thermal stabilization of the triple helix is
      the direct result of a coordination complex between Fe(III) and the hydroxamate
      groups tethered to the C termini of the collagen mimetic peptide chains.

PMID- 16441101
TI  - Thioamide pincer ligands with charge versatility.
AB  - This paper reports the synthesis and characterization of three complexes, two
      palladium and one platinum, with 2,6-bis-thioamido-phenyl and 2,6-bis-thioamido
      pyridine ligands. The ligands show internal charge versatility by losing protons
      from a phenyl CH (I) or from amide NH's (II and III). The complexes were also
      examined as Heck catalysts, and the palladacycle, I, was found to be more
      effective compared to the others. The crystal structures of the complexes are
      also reported.

PMID- 16441102
TI  - Understanding the origin of metal-sulfur vibrations in an oxo-molybdenum
      dithiolene complex: relevance to sulfite oxidase.
AB  - X-ray crystallography and resonance Raman (rR) spectroscopy have been used to
      further characterize (Tp*)MoO(qdt) (Tp* is hydrotris(3,5-dimethyl-1
      pyrazolyl)borate and qdt is 2,3-quinoxalinedithiolene), which represents an
      important benchmark oxomolybdenum mono-dithiolene model system relevant to
      various pyranopterin Mo enzyme active sites, including sulfite oxidase. The
      compound (Tp*)MoO(qdt) crystallizes in the triclinic space group, P1, where a =
      9.8424 (7) A, b = 11.2323 (8) A, c = 11.9408 (8) A, alpha = 92.7560 (10) degrees,
      beta = 98.9530 (10) degrees, and gamma = 104.1680 (10) degrees. The (Tp*)MoO(qdt)
      molecule exhibits the distorted six-coordinate geometry characteristic of related
      oxo-Mo(V) systems possessing a single coordinated dithiolene ligand. The first
      coordination sphere bond lengths and angles in (Tp*)MoO(qdt) are very similar to
      the corresponding structural parameters for (Tp*)MoO(bdt) (bdt is 1,2
      benzenedithiolene). The relatively small inner-sphere structural variations
      observed between (Tp*)MoO(qdt) and (Tp*)MoO(bdt) strongly suggest that geometric
      effects are not a major contributor to the significant electronic structural
      differences reported for these two oxo-Mo(V) dithiolenes. Therefore, the large
      differences observed in the reduction potential and first ionization energy
      between the two molecules appear to derive primarily from differences in the
      effective nuclear charges of their respective sulfur donors. However, a subtle
      perturbation to Mo-S bonding is implied by the nonplanarity of the dithiolene
      chelate ring, which is defined by the fold angle. This angular distortion (theta
      = 29.5 degrees in (Tp*)MoO(qdt); 21.3 degrees in (Tp*)MoO(bdt)) observed between
      the MoS2 and S-C=C-S planes may contribute to the electronic structure of these
      oxo-Mo dithiolene systems by controlling the extent of S p-Mo d orbital overlap.
      In enzymes, the fold angle may be dynamically modulated by the pyranopterin,
      thereby functioning as a transducer of vibrational energy associated with protein
      conformational changes directly to the active site via changes in the fold angle.
      This process could effectively mediate charge redistribution at the active site
      during the course of atom- and electron-transfer processes. The rR spectrum shows
      bands at 348 and 407 cm(-1). From frequency analysis of the normal modes of the
      model, [(NH3)3MoO(qdt)]1+, using the Gaussian03 suite of programs, these bands
      are assigned as mixed-mode Mo-S vibrations of the five-membered Mo-ditholene core
      structure. Raman spectroscopy has also provided additional evidence for an in
      plane pseudo-sigma dithiolene S-Mo d(xy) covalent bonding interaction in
      (Tp*)MoO(qdt) and related oxo-Mo-dithiolenes that has implications for electron
      transfer regeneration of the active site in sulfite oxidase involving the
      pyranopterin dithiolene.

PMID- 16441103
TI  - Rational design and synthesis of porous organic-inorganic hybrid frameworks
      constructed by 1,3,5-benzenetriphosphonic acid and pyridine synthons.
AB  - 1,3,5-Benzenetriphosphonic acid, H6BTP, 1,3,5-[(HO)2OP]3C6H3, was reacted
      hydrothermally with copper salts in the absence and presence of 4,4'-bipyridine
      (bpy) and 4,4'-trimethlyenedipyridine (tbpy) in a 1:1 molar ratio leading to
      three new organic-inorganic hybrid frameworks. Compound 1,
      {Cu6[C6H3(PO3)3]2(H2O)8} x 5.5 H2O, has three different copper ions that are
      interconnected by the highly charged [1,3,5-(PO3)3C6H3]6- anionic moieties. These
      moieties self-assemble through tetra-copper units to give a cagelike motif with
      two benzene rings parallel to each other at a distance of 3.531 A which extend
      along the a axis and link with a grouping of four-coordinated copper units in the
      b axis direction to give the cross-linked layered structure. In compound 2,
      Cu{C6H3[PO(OH)O]2[PO(OH)2]}(C10H8N2), the copper ions are in square pyramidal
      geometries and are interconnected via chelating and bridging BTP ligands into
      layers which are further cross-linked by bpy ligands into a pillared layered
      architecture. Compound 3, {Cu2C6H3[PO(OH)O]2[PO3](C13H14N2)} x 3 H2O x 0.5
      HCON(CH3)2, contains tetra-copper units that are linked by BTP ligands and
      further linked by tbpy linkers in the c axis direction to produce a large channel
      sized 3D framework.

PMID- 16441104
TI  - Crown bowl: metallocyclophane by self-assembly of 4'-pyridylmethyl-armed 12-crown
      4 ethers with Ag+ ions.
AB  - New 3'-pyridylmethyl- and 4'-pyridylmethyl-armed monoaza-12-crown-4 ethers were
      prepared by the reductive amination of monoaza-12-crown-4 with the appropriate
      pyridinecarbaldehyde in the presence of NaBH(OAc)3. X-ray crystallography, cold
      electrospray ionization mass spectrometry, and 1H NMR titration experiments show
      that Ag+ complexes with 3'-pyridylmethyl- and 4'-pyridylmethyl-armed monoaza-12
      crown-4 ethers are dimetallo[3.3]metacyclophane and
      trimetallo[3.3.3]paracyclophane, respectively (crown bowl). The structure of the
      metallocyclophanes can be controlled by the positions of the N atoms in the
      pyridine side arms and the ring size of the crown moiety.

PMID- 16441105
TI  - Synthesis and redox properties of crowded triarylphosphines possessing ferrocenyl
      groups.
AB  - Crowded triarylphosphines possessing ferrocenyl groups [(4-ferrocenyl-2,6
      diisopropylphenyl)(n)(2,4,6-triisopropylphenyl)(3-n)P (5a, n = 1; 5b, n = 2; 5c,
      n = 3)] were synthesized by the reaction of the corresponding arylcopper(I)
      reagents with the diarylchlorophosphines. Structures of the triarylphosphines
      were studied by 1H, 13C, and 31P NMR spectroscopies, and the characteristic
      patterns of the proton signals of the 2,6-isopropyl groups and upfielded 31P
      chemical shifts suggest structural similarities of the triarylphosphine moiety to
      the previously reported tris(2,4,6-triisopropylphenyl)phosphine (2). X-ray
      crystallography of 5c also revealed that the structure around the phosphorus is
      similar to that of 1, where the average bond angle and length around the
      phosphorus atom are 110.8 degrees and 1.854 A, respectively. According to the
      electrochemical measurements, phosphines 5a, 5b, and 5c are reversibly oxidized
      in two, three, and four steps, respectively, which suggests significant
      electronic interaction among the triarylphosphine and the ferrocene redox centers
      as well as weak interaction among the ferrocene redox centers. The EPR spectra
      obtained at cryogenic temperature after oxidation of phosphines 5a, 5b, and 5c
      are superpositions of those for the cation radicals of the crowded
      triarylphosphine and ferricinium. The solution spectra obtained at 293 K, which
      consist of two lines typical of the cation radical of the crowded
      triarylphosphines, become weaker as the number of the ferrocenyl groups increases
      and the cation radical of 5c does not show EPR signals. These findings suggest
      not only instability of the tetra(cation radical) of 5c but also the course of
      oxidation where the ferrocenyl groups in the periphery of the molecules are
      oxidized at first.

PMID- 16441106
TI  - Tuning the magnetic behavior via dehydration/hydration treatment of a new
      ferrimagnet with the composition of K0.2Mn1.4Cr(CN)6 x 6H2O.
AB  - A new complex (1) of Prussian blue analogue with the composition of
      K0.2Mn1.4Cr(CN)6 x 6H2O was prepared and characterized structurally as well as
      magnetically. The crystal structure of complex 1 was determined by X-ray
      diffraction analysis. The results indicate that complex 1 consists of a 3D cubic
      lattice similar to those of Mn3[Cr(CN)6]2 x xH2O, Mn3[Co(CN)6]2 x xH2O,
      Cd3[Cr(CN)6]2 x xH2O, and Cd3[Co(CN)6]2 x xH2O. Magnetic measurements show that
      complex 1 is a ferrimagnet with T(c) = 66 K. It is interesting to note that the
      magnetic behavior of complex 1 can be substantially modulated through a
      dehydration/rehydration treatment. The T(c) value of this ferrimagnet increases
      to 99 K after dehydration reaching a 23.4% weight loss, and it decreases back to
      66 K after the dehydrated sample reabsorbs water molecules.

PMID- 16441108
TI  - Malonate-containing manganese(III) complexes: synthesis, crystal structure, and
      magnetic properties of AsPh4[Mn(mal)2(H2O)2].
AB  - The novel manganese(III) complexes PPh4[Mn(mal)2(H2O)2] (1) and
      AsPh4[Mn(mal)2(H2O)2] (2) (PPh4+ = tetraphenylphosphonium cation, AsPh4+ =
      tetraphenylarsonium cation, and H2mal = malonic acid) have been prepared, and the
      structure of 2 was determined by X-ray diffraction analysis. 2 is a mononuclear
      complex whose structure is made up of trans-diaquabis(malonato)manganate(III)
      units and tetraphenylarsonium cations. Two crystallographically independent
      manganese(III) ions (Mn(1) and Mn(2)) occur in 2 that exhibit elongated
      octahedral surroundings with four oxygen atoms from two bidentate malonate groups
      in equatorial positions (Mn(1)-O = 1.923(6) and 1.9328(6) A and Mn(2)-O =
      1.894(6) and 1.925(6) A) and two trans-coordinated water molecules in the axial
      sites (Mn(1)-Ow = 2.245(6) A and Mn(2)-Ow = 2.268(6) A). The [Mn(mal)2(H2O)2]-
      units are linked through hydrogen bonds involving the free malonate-oxygen atoms
      and the coordinated water molecules to yield a quasi-square-type anionic layer
      growing in the ab plane. The shortest intralayer metal-metal separations are
      7.1557(7) and 7.1526(7) A (through the edges of the square). The anionic sheets
      are separated from each other by layers of AsPh4+ where sextuple- and double
      phenyl embraces occur. The magnetic behavior of 1 and 2 in the temperature range
      1.9-290 K reveals the occurrence of weak intralayer ferromagnetic interactions (J
      = +0.081(1) (1) and +0.072(2) cm(-1) (2)). These values are compared to those of
      the weak antiferromagnetic coupling [J = -0.19(1) cm(-1)], which is observed in
      the chain compound K2[Mn(mal)2(MeOH)2][Mn(mal)2] (3), where the exchange pathway
      involves the carboxyate-malonate bridge in the anti-syn conformation. The
      structure of 3 was reported elsewhere. Theoretical calculations on fragment
      models of 2 and 3 were performed to analyze and substantiate both the nature and
      magnitude of the magnetic couplings observed.

PMID- 16441107
TI  - Electronic effects of electron-donating and -withdrawing groups in model
      complexes for iron-tyrosine-containing metalloenzymes.
AB  - Three new iron(III) complexes with the ligand N,N'-bis(2-hydroxybenzyl)-N,N'
      bis(pyridin-2-ylmethyl)ethylenediamine, H2bbpen, containing electron-donating and
      -withdrawing groups (Me, Br, NO2) in the 5-position of the phenol rings were
      synthesized and fully characterized by IR spectroscopy, ESI mass spectrometry,
      and CHN elemental analyses. X-ray structures of the iron(III) complexes
      containing NO2 and Me groups were determined. The effects of the substituents on
      the electronic properties of the complexes were detected by UV-visible
      spectroscopy, cyclic voltammetry, and X-ray crystallography. Linear correlations
      between the Hammett parameter for the substituents (sigma(p)) and the
      Fe(III)/Fe(II) redox potentials or ligand-metal charge-transfer (LMCT) processes
      of the complexes were obtained. A theoretical study using DFT is presented and
      shows good agreement between the experimental and calculated data.

PMID- 16441109
TI  - Influence of lattice interactions on the Jahn-Teller distortion of the
      [Cu(H2O)6]2+ ion: dependence of the crystal structure of
      K2[Cu(H2O)6](SO4)(2x)(SeO4)(2-2x) upon the sulfate/selenate ratio.
AB  - The temperature dependence of the structure of the mixed-anion Tutton salt
      K2[Cu(H2O)6](SO4)(2x)(SeO4)(2-2x) has been determined for crystals with 0, 17,
      25, 68, 78, and 100% sulfate over the temperature range of 85-320 K. In every
      case, the [Cu(H2O)6]2+ ion adopts a tetragonally elongated coordination geometry
      with an orthorhombic distortion. However, for the compounds with 0, 17, and 25%
      sulfate, the long and intermediate bonds occur on a different pair of water
      molecules from those with 68, 78, and 100% sulfate. A thermal equilibrium between
      the two forms is observed for each crystal, with this developing more readily as
      the proportions of the two counterions become more similar. Attempts to prepare a
      crystal with approximately equal amounts of sulfate and selenate were
      unsuccessful. The temperature dependence of the bond lengths has been analyzed
      using a model in which the Jahn-Teller potential surface of the [Cu(H2O)6]2+ ion
      is perturbed by a lattice-strain interaction. The magnitude and sign of the
      orthorhombic component of this strain interaction depends on the proportion of
      sulfate to selenate. Significant deviations from Boltzmann statistics are
      observed for those crystals exhibiting a large temperature dependence of the
      average bond lengths, and this may be explained by cooperative interactions
      between neighboring complexes.

PMID- 16441110
TI  - Three-dimensional nets from star-shaped hexakis(arylthio)triphenylene molecules
      and silver(I) salts.
AB  - This article reports a number of functional 3D networks based on the coordination
      bonds between the silver(I) ion and polycyclic aromatic 2,3,6,7,10,11
      hexakis(organylthio)triphenylene (HRTT) molecules. First, 2,3,6,7,10,11
      hexakis(phenylthio)triphenylene (HPhTT) chelates with AgBF4 (or AgTf, where Tf is
      triflate) in the presence of hexafluorobenzene to form a 3D network (composition,
      HPhTT x AgBF4; space group, I4), where each Ag(I) atom is bonded to three HPhTT
      molecules and acts as a three-connected node that interconnects the trigonal
      HPhTT ligands. In addition to the relatively rare 8(2) x 10-a topology, the
      network features distinct channel-like domains that incorporate various solvent
      molecules (e.g., acetone and tetrahydrofuran). The solvent molecules can be
      evacuated to produce a stable and crystalline apohost network, in which the
      solvent-accessible fraction of the cell volume is calculated to be about 16%.
      Second, chelation of 2,3,6,7,10,11-hexakis(4-methoxyphenylthio)triphenylene
      (HMOPhTT) and AgSbF6 in a 1:1 ratio results in a 3D network featuring a similar
      8(2) x 10-a topology and Ag(I) coordination environment. However, the
      crystallographic symmetry (space group Cc) is lowered, and the feature of
      porosity is much less distinct. The 3D networks show strong room-temperature
      fluorescence bands with lambda(F,max) = 450 nm, due to the pi-electron fragment
      of the triphenylene group.

PMID- 16441111
TI  - Coordination of XeF2 to calcium and cadmium hexafluorophosphates(V).
AB  - [M(XeF2)5](PF6)2 (M = Ca, Cd) complexes were prepared by the reaction of MF2 and
      XeF2 under pressure of gaseous PF5 in anhydrous HF as solvent. The coordination
      sphere of the Ca atom consists of nine fluorine atoms: three from two PF6(-)
      units (one bidentate and one monodentate) and one from each of six XeF2
      molecules. The coordination sphere of the Cd atom consists of eight fluorine
      atoms: one from each of two PF6(-) units and one from each of six XeF2 molecules.
      Two of the XeF2 ligands about M in each compound are bridging ligands and are
      each linked to two M, generating infinite (-M-F-Xe-F-M-F-Xe-F-) chains along the
      b-axis in the Ca salt and along the c-axis in the Cd compound. The Cd2+ cation is
      smaller and more electronegative than the Ca2+ cation. These differences account
      for the higher F ligand coordination in the Ca2+ salt and for other structural
      features that distinguish them. The different stoichiometry of the PF6(-) salts
      when compared with their AsF6(-) analogues, which have the composition
      [M(XeF2)4](AsF6)2 (M = Ca, Cd), is in accord with the lower F ligand charge in
      the AsF6(-) when compared with that in the PF6(-) compound. Indeed, the AsF6(-)
      ligand charges appear to be similar to those in the XeF2-bridged species.

PMID- 16441112
TI  - Solid-state structural characterization of a rigid framework of lacunary
      heteropolyniobates.
AB  - In our ongoing investigations of heteropolyniobate chemistry, a phase featuring
      decorated, A-type trivacant alpha-Keggin ions linked by their charge-balancing
      sodium cations has been isolated and structurally characterized. This is the
      first heteropolyniobate reported that has a true lacunary structure type.
      Na15[(PO2)3PNb9O34] x 22 H2O (1) [triclinic space group P1 (No. 2); a = 12.242
      (2) A, b = 12.291 (3) A, c = 22.056 (4) A; alpha = 93.12 (3) degrees, beta =
      99.78 (3) degrees, gamma = 119.84 (3) degrees; Z = 4, V = 2799.2 (10) A3] is
      composed of bilayers of the heteropolyanions alternating with layers of hydrated
      Na+ cations. Sodium cations also bridge the clusters within their layers through
      Na-O(t)-Nb, Na-O(b)-Nb2, and Na-O(t)-P bonds (t = terminal and b = bridging).
      This phase is poorly soluble in water, suggesting that it is more characteristic
      of a framework of linked heteropolyanions rather than a water-soluble
      heteropolyanion salt. Two-dimensional solid-state 23Na multiple-quantum magic
      angle spinning (MAS) NMR of 1 reveals five distinctive chemical and structural
      environments for sodium, which agrees with the crystallographic data. The 23Na
      and 1H MAS NMR studies further illustrate the rigid and immobile nature of this
      framework of cations and anions.

PMID- 16441113
TI  - Kinetics of the reaction of chromium(VI) with tris(1,10-phenanthroline)iron(II)
      ions in acidic solutions. Anion and medium effects: perchlorate versus triflate.
AB  - Reinvestigation of the reaction between title reagents in aqueous acidic triflate
      and perchlorate media revealed an unusual difference: the reaction is strictly
      first-order with respect to the concentration of Fe(phen)3(2+) (phen = 1,10
      phenanthroline) in the triflate medium but shows an additional, but we believe
      artifactual, higher-order term in the perchlorate medium. We postulate that the
      apparent orders with respect to [Fe(phen)3(2+)] in (H/Li)ClO4 do not indicate the
      actual chemical mechanism but, in whole or in part, the orders, particularly the
      higher-order component, reflect an interaction specific to Fe(phen)3(2+) or
      Fe(phen)3(3+) and ClO4(-) in solution. Data in (H/Li)O3SCF3 solutions indicate
      that, in the absence of added Fe(phen)3(3+), the first of the three sequential
      electron-transfer steps is rate controlling. Reactions started in the presence of
      the product Fe(phen)3(3+) occur somewhat more slowly, suggesting the first
      electron transfer is reversible. This finding allows the relative rate constants
      for Cr(V) oxidation and reduction to be evaluated, with limited precision, by two
      methods of analysis. The dependences on [Cr(VI)] can be resolved into
      contributions from the species HCrO4(-) and Cr2O7(2-), each of which in turn
      depends on [H+]. The reaction mechanism is discussed in light of the data
      obtained in the triflate medium. Further, the rate constants for certain steps
      can be considered in light of E0 for the Cr(VI)/(V) couple.

PMID- 16441114
TI  - Synthesis, structural characterization, and theoretical studies of gold(I) and
      gold(I)-gold(III) thiolate complexes: quenching of gold(I) thiolate luminescence.
AB  - The gold(I) thiolate complexes [Au(2-SC6H4NH2)(PPh3)] (1), [PPN][Au(2-SC6H4NH2)2]
      (2) (PPN = PPh3=N=PPh3), and [{Au(2-SC6H4NH2)}2(mu-dppm)] (3) (dppm =
      PPh2CH2PPh2) have been prepared by reaction of acetylacetonato gold(I) precursors
      with 2-aminobenzenethiol in the appropriate molar ratio. All products are
      intensely photoluminescent at 77 K. The molecular structure of the dinuclear
      derivative 3 displays a gold-gold intramolecular contact of 3.1346(4) A. Further
      reaction with the organometallic gold(III) complex [Au(C6F5)3(tht)] affords
      dinuclear or tetranuclear mixed gold(I)-gold(III) derivatives with a thiolate
      bridge, namely, [(AuPPh3){Au(C6F5)3}(mu2-2-SC6H4NH2)] (4) and [(C6F5)3Au(mu2-2
      SC6H4NH2)(AudppmAu)(mu2-2-SC(6)H4NH2)Au(C6F5)3] (5). X-ray diffraction studies of
      the latter show a shortening of the intramolecular gold(I)-gold(I) contact
      [2.9353(7) or 2.9332(7) A for a second independent molecule], and short gold(I)
      gold(III) distances of 3.2812(7) and 3.3822(7) A [or 3.2923(7) and 3.4052(7) A]
      are also displayed. Despite the gold-gold interactions, the mixed derivatives are
      nonemissive compounds. Therefore, the complexes were studied by DFT methods. The
      HOMOs and LUMOs for gold(I) derivatives 1 and 3 are mainly centered on the
      thiolate and phosphine (or the second thiolate for complex 2), respectively, with
      some gold contributions, whereas the LUMO for derivative 4 is more centered on
      the gold(III) fragment. TD-DFT results show a good agreement with the
      experimental UV-vis absorption and excitation spectra. The excitations can be
      assigned as a S --> Au-P charge transfer with some mixture of LLCT for derivative
      1, an LLCT mixed with ILCT for derivative 2, and a S --> Au...Au-P charge
      transfer with LLCT and MC for derivative 3. An LMCT (thiolate --> Au(III) mixed
      with thiolate --> Au-P) excitation was found for derivative 4. The differing
      nature of the excited states [participation of the gold(III) fragment and the
      small contribution of sulfur] is proposed to be responsible for quenching the
      luminescence.

PMID- 16441115
TI  - Supramolecular assemblies with calix[6]arenes and copper ions: from dinuclear to
      trinuclear linear arrangements of hydroxo-Cu(II) complexes.
AB  - Complexation of copper(II) by calix[6]arene-based ligands bearing either two or
      three N-benzylimidazole coordinating arms under basic conditions has been
      studied. Whereas the tris(imidazole) derivative stabilizes dicationic 5
      coordinate aqua complexes in a mononuclear state with an intracavity bound guest,
      in the presence of hydroxide ions, the latter undergo dimerization. An X-ray
      structure revealed decoordination of one imidazole arm and formation of a
      bis(hydroxo) bridged Cu(II) core with a square-planar geometry for both metal
      centers sandwiched by two empty calixarene cavities. Upon methanolysis, the
      dinuclear complex underwent an unexpected rearrangement leading to the clean
      formation of a trinuclear complex. X-ray diffraction analyses of this novel
      species revealed a trinuclear core constructed around a central Cu(II) ion that
      is doubly bridged through either methoxide or hydroxide anions to two Cu(II) ions
      hold by two calixarene units. The same complex could be directly synthesized by
      reacting the ligand with copper(II) perchlorate in a 2:3 ratio in the presence of
      base. In solution, the tetrahydroxo Cu(3) complex was characterized by UV-vis and
      (1)H NMR spectroscopies and displayed an electron paramagnetic resonance (EPR)
      signal only below 100 K that accounts for a S = 1/2 fundamental state. Formation
      of the same di- and trinuclear species was observed with a calix[6]arene-based
      bis(imidazole) ligand, which demonstrates the generality of the reaction schemes.
      All these results emphasize the versatility of the calix[6]arene scaffold for the
      stabilization of metal complexes with various nuclearities.

PMID- 16441116
TI  - Terephthalamide-containing analogues of TREN-Me-3,2-HOPO.
AB  - A series of terephthalamide-containing analogues based on TREN-Me-3,2-HOPO have
      been prepared. These analogues contain one, two, or three bidentate 2,3
      dihydroxyterephthalamide (TAM) units in place of the 3,2-hydroxypyridinone (HOPO)
      units on the parent hexadentate ligand. One representative ligand in the series,
      TRENHOPOTAM2, and its gallium complex have been structurally characterized by X
      ray diffraction. TRENHOPOTAM2 crystallizes in the monoclinic space group P2(1)/c
      with cell parameters a = 16.0340(17) A, b = 17.0609(18) A, c = 16.0695(17) A,
      beta = 113.837(2) degrees, and Z = 4. Ga[TRENHOPOTAM2] also crystallizes in the
      monoclinic space group P2(1)/c, with cell parameters a = 16.3379(14) A, b =
      15.2722(13) A, c = 19.4397(17) A, beta = 91.656(2) degrees, and Z = 4. The
      conformation of the TRENHOPOTAM2 ligand structure suggests that the ligand is
      predisposed for metal ion binding. The aqueous protonation and ferric ion
      coordination chemistry of all ligands in the series were examined using
      potentiometric and spectrophotometric methods, giving log formation constants of
      34.6(2) (beta110) and 38.8(2) (beta111) for the ferric TRENHOPO2TAM complexes,
      41.0(3) (beta110) and 45.4(3) (beta111) for the ferric TRENHOPOTAM2 complexes,
      and 45.2(2) (beta110) and 50.9(2) (beta111) for the ferric TRENTAM3 complexes.
      These thermodynamic data confirm that adding terephthalamide units to a
      hydroxypyridinone-containing ligand tends to increase the stability of the
      resulting iron complex. The ferric TRENTAM3 complex is one of the most stable
      iron complexes yet reported.

PMID- 16441117
TI  - Donor-acceptor heteroleptic open sandwiches.
AB  - A series of donor-acceptor heteroleptic open sandwiches with formula CpM-M'Pyl (M
      = B, Al, Ga; M' = Li, Na; Cp = cyclopentadienyl; Pyl = pentadienyl) has been
      designed in silico using density functional theory. The most stable complexes are
      those containing boron as a donor atom. A molecular orbital analysis shows that
      the s character of the lone pair located at the group 13 element is mainly
      responsible for the complex stabilization. It is also found that the surrounding
      medium has a similar effect on these sandwiches such as in the "classical" donor
      acceptor complexes, showing a decrement in the group 13 element-alkaline metal
      bond lengths.

PMID- 16441118
TI  - Dehydrogenative silane coupling on silicon surfaces via early transition metal
      catalysis.
AB  - Derivatization of silicon surfaces is an area of intense interest due to the
      centrality of silicon in the microelectronics industry and because of potential
      promise for a myriad of other applications. In this paper, we investigate the
      feasibility of Si-Si bond formation directly on the surface to contrast with the
      more widely studied Si-C and Si-O bond forming reactions. Functionalization of
      hydride-terminated silicon surfaces with silanes is carried out via early
      transition metal mediated dehydrogenative silane coupling reactions. Zirconocene
      and titanocene catalyst systems were evaluated for heterocoupling of a molecular
      silane, RSiH3, with a surface Si-H group on Si(s). The zirconocene catalysts
      proved to be much more reactive than the titanium system, and so the former was
      examined exclusively. The silanes, aromatic or aliphatic, are bonded to the
      silicon surface through direct Si-Si bonds, although the level of incorporation
      of the trihydroarylsilanes was substantially higher than that of the aliphatic
      silanes. The reaction proceeds on nanocrystalline hydride-terminated porous
      silicon surfaces, as well as flat Si(100)-H(x) and Si(111)-H interfaces. The
      reactions were studied by a variety of techniques, including FTIR, SIMS, and XPS.

PMID- 16441119
TI  - Unprecedented [V2O]6+ core of a centrosymmetric thiosemicarbazonato dimer:
      spontaneous deoxygenation of oxovanadium(IV).
AB  - The complex cation [{V(daptsc)(MeOH)}2(mu-O)]2+ [daptsc(2-) = 2,6
      diacetylpyridine bis(thiosemicarbazonate)] is the first crystallographically
      elucidated dimer to possess a [V2O]6+ core, the [V(IV)-O-V(IV)]6+ structural
      unit, formed by cleavage of the multiple bond in the oxo-cation VO2+, is linear
      with the oxo group residing on a crystallographic center of inversion, and the
      temperature dependence of the magnetic data of the dimer is consistent with weak
      antiferromagnetic coupling of the d1-d1 centers.

PMID- 16441120
TI  - Synthesis of heterometal cluster complexes by the reaction of
      cobaltadichalcogenolato complexes with groups 6 and 8 metal carbonyls.
AB  - Metalladichalcogenolate cluster complexes [{CpCo(S2C6H4)}2Mo(CO)2] (Cp = eta(5)
      C5H5) (3), [{CpCo(S2C6H4)}2W(CO)2] (4), [CpCo(S2C6H4)Fe(CO)3] (5),
      [CpCo(S2C6H4)Ru(CO)2(P(t)Bu3)] (6), [{CpCo(Se2C6H4)}2Mo(CO)2] (7), and
      [{CpCo(Se2C6H4)}(Se2C6H4)W(CO)2] (8) were synthesized by the reaction of
      [CpCo(E2C6H4)] (E = S, Se) with [M(CO)3(py)3] (M = Mo, W), [Fe(CO)5], or
      [Ru(CO)3(P(t)Bu3)2], and their crystal structures and physical properties were
      investigated. In the series of trinuclear group 6 metal-Co complexes, 3, 4, and 7
      have similar structures, but the W-Se complex, 8, eliminates one cobalt atom and
      one cyclopentadienyl group from the sulfur analogue, 4, and does not satisfy the
      18-electron rule. 1H NMR observation suggested that the CoW dinuclear complex 8
      was generated via a trinuclear Co2W complex, with a structure comparable to 7.
      The trinuclear cluster complexes, 3, 4, and 7, undergo quasi-reversible two-step
      one-electron reduction, indicating the formation of mixed-valence complexes
      Co(III)M(0)Co(II) (M = Mo, W). The thermodynamic stability of the mixed-valence
      state increases in the order 4 < 3 < 7. In the dinuclear group 8 metal-Co
      complexes, 5 and 6, the CpCo(S2C6H4) moiety and the metal carbonyl moiety act as
      a Lewis acid character and a base character, respectively, as determined by their
      spectrochemical and redox properties. Complex 5 undergoes reversible two-step one
      electron reduction, and an electron paramagnetic resonance (EPR) study indicates
      the stepwise reduction process from Co(III)Fe(0) to form Co(III)Fe(-I) and
      Co(II)Fe(-I).

PMID- 16441121
TI  - Nature of the chemical bond in polypnictides: the lone pair aromatic anions P4(2
      ) and As4(2-).
AB  - The nature of the chemical bond in inorganic 6pi aromatic systems such as P4(2-),
      S4(2+), or S2N2 is a matter of particular interest because the phenomenon of
      aromaticity is not as well established in these compounds as it is in the classic
      aromatic hydrocarbons. Here we present the synthesis, NMR spectra, and crystal
      structures of bis(potassium(18-crown-6))cyclotetraphosphide-ammonia(1/2) (K@18
      crown-6)2P4 x 2 NH3, bis(rubidium(18-crown-6))cyclotetraphosphide
      cyclotetraarsenide-ammonia(1/3) (Rb@18-crown-6)2(P4)0.85(As4)0.15 x 3 NH3, both
      containing the 6pi aromatic cyclotetraphosphide anion, P4(2-), and the synthesis
      and crystal structure of bis(potassium(18-crown-6))cyclotetraarsenide (K@18-crown
      6)2As4. As a common motive, all three compounds feature neutral molecules with a
      tripledecker-like coordination of the cyclotetrapnictide anion between two crown
      ether-coordinated alkali metal cations. With ab initio calculations on the HF
      level and by employing the concept of the electron localization function ELF, we
      established that the cyclotetraarsenide anion, As4(2-), shows electron
      delocalization primarily through the lone pairs, as does P4(2-), and may
      consequently also be described as lone pair aromatic.

PMID- 16441122
TI  - Incorporation of triazacyclononane into the metal phosphonate backbones.
AB  - This paper reports the syntheses and crystal structures of a manganese and a
      uranyl phosphonate based on 1,4,7-triazacyclononane-1,4,7-triyl
      tris(methylenephosphonic acid), namely, Mn3{C9N3H18(PO3)3}(H2O)6 x 1.5 H2O (1)
      and UO2{C9N3H19(PO3H)3} x H2O (2). Compound 1 shows a unique layer structure
      where the hydrophobic triazacyclononane moieties all reside on one side of the
      inorganic backbone of the manganese phosphonate layer while the hydrophilic
      coordinated water molecules reside on the other side. In compound 2, the
      triazacyclononane moieties are immobilized on the inorganic backbone of the
      uranyl phosphonate chains. The magnetic properties of compound 1 and the ion
      exchange properties of compound 2 have been studied.

PMID- 16441123
TI  - Supramolecular asymmetric induction in dinuclear triple-stranded helicates.
AB  - Supramolecular chiral induction has been observed in five dinuclear triple
      stranded helicates composed entirely of achiral components. Three different
      chiral cations were found to be very effective at inducing high levels of
      enantiomeric enrichment in racemic mixtures of the helicates. The mechanism of
      intermolecular chiral induction in one cation-helicate pair, s-nic/K6[Ga2L(1)3],
      has been elucidated through circular dichroism spectroscopy, X-ray
      crystallography, and one and two-dimensional NMR spectroscopy (s-nic = N-methyl-s
      nicotinium, H4L(1) = 1,4-bis(2',3'-dihydroxybenzamido)phenylene).

PMID- 16441124
TI  - Color tuning of a nickel complex with a novel N2S2 pyridine-containing
      macrocyclic ligand.
AB  - The novel pyridine-containing 14-membered macrocycle 3,11-dithia-7,17
      diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L), which contains an N2S2
      donor set, was synthesized, and its protonation behavior was studied by
      absorption titration with CH3SO3H. The reaction of L with Pd(II) was studied
      spectroscopically, and the square-planar complex [Pd(L)](BF4) was isolated and
      characterized. The reactions between L and NiX2 x 6 H2O (X = BF4, ClO4) in
      ethanol or acetonitrile afforded the octahedral complexes [Ni(CH3CN)(H2O)(L)](X)2
      and [Ni(H2O)2(L)](X)2, respectively. The square-planar complexes [Ni(L)](X)2 were
      obtained by heating these octahedral complexes. Spectrophotometric titrations of
      [Ni(L)](BF4)2 were performed with neutral and negatively charged ligands. The
      color of nitromethane solutions of this square-planar complex turns from red to
      cyan, purple, blue, yellow-green, and pink following addition of halides,
      acetonitrile, water, pyridine, and 2,2'-bipyridine, respectively. X-ray
      structural analyses were carried out on the
      {[Ni(ClO4)(H2O)(L)][Ni(H2O)2(L)]}(ClO4)3, [Ni(CH3CN)(H2O)(L)](ClO4)2,
      [{Ni(L)}2(mu-Cl)2](ClO4)2, and [{Ni(L)}2(mu-Br)2]Br2 x 2 CH3NO2 complexes.

PMID- 16441125
TI  - Coordination networks with fluorinated backbones.
AB  - Fluorine-containing ligands 2,3,5,6-tetrafluoro-1,4-bis(imidazol-1-yl
      methyl)benzene (1) and 2,3,5,6-tetrafluoro-1,4-bis(2-methylimidazol-1-yl
      methyl)benzene (2) were prepared and coordinated with AgNO3, Co(ClO4)2 x 6 H2O,
      and Cd(NO3)2 x 4 H2O, respectively, to form the following structures: 3D channel
      polymer [Ag2(1)2(NO3)2 x H2O x MeOH]n (3), 2D sheet polymer [Co(1)3(ClO4)2]n (4),
      1D chain polymer [Cd(1)3(NO3)2 x 4 H2O]n (5), and a 2D herringbone sheet polymer
      [Ag(2)NO3 x 1.5 MeOH]n (6). The solid-state crystal structures of 3-6 were
      studied by single-crystal X-ray crystallography.

PMID- 16441126
TI  - From simple monopyridine clusters [Mo6Br13(Py-R)][n-Bu4N] and hexapyridine
      clusters [Mo6X8(Py-R)6][OSO2CF3]4 (X = Br or I) to cluster-cored organometallic
      stars, dendrons, and dendrimers.
AB  - Hexasubstitution of apical triflate ligands in the octahedral clusters
      [M]2[Mo6X8(CF3SO3)6] (M = n-Bu4N or Cs, X = Br or I) and monosubstitution in [n
      Bu4N]2[Mo6Br13(CF3SO3)] was carried out in tetrahydrofuran at 60 degrees C with
      simple pyridines and then extended to organometallic pyridines, yielding cluster
      cored stars, and to dendronic polyallyl- and polyferrocenylpyridines, yielding
      cluster-cored polyallyl and polyferrocenyl dendrimers and dendrons. The orange
      pyridine-substituted clusters, whose pyridine protons are deshielded in 1H NMR (a
      practical tool for characterization), are air-stable and thermally stable with
      simple pyridines, light- and air-sensitive with organometallic pyridines, and air
      fragile and thermally fragile with large dendronized pyridines.

PMID- 16441127
TI  - Structure of an I- x (H2O)6 anion cluster in a 3D anion crystal host [I x
      (H2O)6Fe(CN)6 x H2O]4-.
AB  - A planar structure of an anion cluster I- x (H2O)6 in a 3D supramolecular complex
      [Ru(bpy)3]2[I x (H2O)6Fe(CN)6 x H2O] has been determined by single-crystal X-ray
      analysis. In the supramolecule, the anion cluster I- x (H2O)6, together with the
      anion [Fe(CN)6 x H2O]2-, acts as a 3D crystal host, and the [Ru(bpy)3]2+ cations,
      as the guest molecules, occupy the vacancies of the 3D host framework. This is
      the first crystal example of the anion cluster I- x (H2O)6.

PMID- 16441128
TI  - Energy transfer in hybrids based on a thiophene-substituted ethynylbipyridine
      dimer decorated with Re(I), Ru(II), and Os(II) units.
AB  - The preparation, structural features, electrochemical behavior, and optical
      properties (at room temperature and at 77 K) are reported for a series of
      thiophene-containing hybrids based on the bent conjugated backbone of a rigid
      ditopic ligand, the dimeric moiety 3,4-dibutyl-2,5-bis{5'-[(3,4-dibutylthien-2
      ylethynyl)-2,2'-bipyridin-5-yl]ethynyl}thiophene (TBTBT). Within the dimer, the
      diethynyl-2,2'-bipyridine units (bpy, the coordination sites) alternate with
      three 3,4-dibuthylthiophene units and coordination of the [Re(CO)3Cl],
      [Ru(bpy)2]2+, and [Os(bpy)2]2+ centers results in the mononuclear species RuTBTBT
      and OsTBTBT and the binuclear species RuTBTBTRu, OsTBTBTOs, RuTBTBTOs, and
      ReTBTBTOs. At room temperature, the emitting states obtained by photoexcitation
      are of 3MLCT nature, and vibronic analysis of the emission spectra indicates that
      they are largely delocalized over the TBTBT ligand. In the binuclear species, the
      intermetal separation is ca. 17 A, and for RuTBTBTOs, an efficient Ru --> Os
      excitation transfer takes place, resulting solely in an Os-based emission. The
      process is ascribed to double-electron transfer (Dexter), as mediated by the
      TBTBT ligand; a similar conclusion holds for the case of ReTBTBTOs. For
      RuTBTBTOs, the process is discussed in some detail also with regard to the
      possibility of disentangling the constituent hole and electron-transfer events.

PMID- 16441129
TI  - Coupled ion/electron hopping in Li(x)NiO2: a 7Li NMR study.
AB  - Deintercalated "Li(x)NiO2" materials (x = 0.25, 0.33, 0.50, 0.58, and 0.65) were
      obtained using the electrochemical route from the Li0.985Ni1.015O2 and
      Li0.993Ni1.007O2 compounds. Refinements of X-ray diffraction data using the
      Rietveld method show a good agreement with the phase diagram of the Li(x)NiO2
      system studied earlier in this laboratory. Electronic conductivity measurements
      show a thermally activated electron-hopping process for the deintercalated
      Li0.5NiO2 phase. In the Li(x)NiO2 materials investigated (x = 0.25, 0.33, 0.50,
      and 0.58), 7Li NMR shows mobility effects leading to an exchanged signal at room
      temperature. A clear tendency for Li to be surrounded mainly by Ni3+ ions with
      the 180 degree configuration is observed, particularly, for strongly
      deintercalated materials with smaller Li+ and Ni3+ contents, even upon heating,
      when this mobility becomes very fast in the NMR time scale. This suggests that
      Li/vacancy hopping does occur on the NMR time scale but that Ni3+/Ni4+ hopping
      does not occur independently. The position of Li seems to govern the oxidation
      state of the Ni around it at any time; the electrons follow the Li ions to
      satisfy local electroneutrality and minimal energy configuration. The observed
      NMR shifts are compatible with the Li/vacancy and Ni3+/Ni4+ ordering patterns
      calculated by Arroyo y de Dompablo et al. for x = 0.25 and x = 0.50, but not for
      x = 0.33 and x = 0.58.

PMID- 16441130
TI  - Toward development of water soluble dye derivatized nitrosyl compounds for
      photochemical delivery of NO.
AB  - This report describes the synthesis, spectroscopy, and photochemistry of a new
      fluorescein-derivatized iron sulfur nitrosyl compound, the Roussin's red salt
      ester bis-((mu-S,mu-S')-fluorescein-2-thioethyl-ester)-tetranitrosyldiiron (Fluor
      RSE). Under continuous photolysis Fluor-RSE decomposes with moderate quantum
      yields (0.0036 +/- 0.0005 at lambda(irr) = 436 nm) with the corresponding release
      of most of the NO carried by the Fe2S2NO4 cluster. Large changes in the optical
      absorptivity occur upon photolysis of the Fluor-RSE, and these changes have been
      attributed to the different protic forms available to the fluorescein chromophore
      as it is separated from the cluster. Steady-state luminescence experiments have
      shown that the fluorescence of Fluor-RSE is about 85% quenched relative to the
      model compound ethyl fluorescein (Fluor-Et). Thus, it is clear that excitation of
      the fluorescein chromophore antennae is followed by energy transfer to the
      Fe/S/NO cluster at a rate at least comparable to fluorescence. However, the
      effect of the iron-sulfur core on the fluorescent lifetimes from fluorescein
      chromophore is much smaller. A single-exponential decay (tau = 3.3 ns) was seen
      for Fluor-RSE that is only modestly shorter than that for Fluor-Et (tau = 4.5
      ns), and this is the effect of the smaller radiative rate constant (k(r)) for the
      former. These systems further demonstrate that attachment of a pendant dye
      chromophore as an antenna significantly improves the effective rate for
      photochemical NO generation from the Roussin's red salt esters at longer
      excitation wavelengths.

PMID- 16441131
TI  - Systematic synthesis and characterization of single-crystal lanthanide
      phenylphosphonate nanorods.
AB  - Using low-temperature hydrothermal methods, nanoscale lanthanide
      phenylphosphonates species with different morphologies, namely, nanoparticles and
      nanorods, have been systematically synthesized. The possible growth mechanism of
      these nanorods was discussed. X-ray diffraction, transmission electron
      microscopy, electron diffraction, and photoluminescence spectra were used to
      characterize these materials. The photoluminescent properties of
      Eu(O3PC6H5)(HO3PC6H5) and La0.91Eu0.09(O3PC6H5)(HO3PC6H5) nanorods were
      discussed.

PMID- 16441132
TI  - Synthesis of variable-aspect-ratio, single-crystalline ZnO nanostructures.
AB  - Variable-aspect-ratio (length/diameter), one-dimensional (1-D) ZnO nanostructures
      (nanorods and nanowires) were prepared in alcohol/water solution by reacting a
      Zn2+ precursor with an organic weak base, tetramethylammonium hydroxide (Me4NOH).
      The effect of the experimental parameters (temperature, base concentration,
      reaction time, and water content) on nucleation, growth, and the final morphology
      of the ZnO nanostructures was investigated. The low-temperature syntheses (75-150
      degrees C) yielded aspect ratios of the 1-D ZnO nanostructures that depended on
      the water content. The individual ZnO nanorods and nanowires were determined to
      be perfect, single crystals with their c axes as the primary growth direction.

PMID- 16441133
TI  - Syntheses and quadratic optical nonlinearities of ruthenium(II) complexes with
      ethynyl-connected N-methylpyridinium electron acceptors.
AB  - We have prepared a number of new dipolar complexes containing ethynyl or buta-1,3
      diynyl units linking electron-rich {Ru(II)(NH3)5}2+, trans-{Ru(II)(NH3)4L}+ (L =
      pyridine or N-methylimidazole), or trans-{Ru(II)Cl(pdma)2}+ [pdma = 1,2
      phenylenebis(dimethylarsine)] centers to pyridinium electron acceptors. In
      acetonitrile solutions at 295 K, the new complexes display unusual blue-shifting
      of their metal-to-ligand charge-transfer (MLCT) bands as the conjugation is
      extended, in a fashion similar to that of the corresponding ethenyl systems.
      Hyper-Rayleigh scattering (HRS) and Stark spectroscopic measurements provide
      direct and indirect estimates of static first hyperpolarizabilities beta0, and
      both the linear and nonlinear optical (NLO) properties are temperature- and
      medium-dependent. Thus, at 77 K in butyronitrile glasses, the MLCT bands display
      more normal red shifts upon conjugation extension. While the Stark-derived beta0
      values generally increase as n (the number of ethynyl units) increases from 0 to
      2, the HRS data show maximization at n = 1 for two of the ammine series but an
      increase upon moving from n = 1 to 2 for the pdma complexes. Comparisons with the
      analogous ethenyl chromophores show that the latter generally display larger
      beta0 values, whether determined via HRS or Stark data, and the inferiority of
      the ethynyl systems in terms of NLO response is more pronounced when n = 2. This
      differing behavior is attributable primarily to larger increases in the
      transition dipole moment mu12 (and, hence, donor-acceptor pi-electronic coupling)
      on elongation in the ethenyl chromophores.

PMID- 16441134
TI  - Has AuF7 been made?
AB  - Quantum chemical calculations at DFT (BP86, B3LYP, BHLYP), MP2, CCSD, and CCSD(T)
      levels have been carried out on various fluoro complexes of gold in oxidation
      states +V through +VII to evaluate the previously claimed existence of AuF7. The
      calculations indicate clearly that elimination of F2 from AuF7 is a strongly
      exothermic reaction with a low activation barrier. This is inconsistent with the
      reported stability of AuF7 up to room temperature. A reported experimental
      vibrational frequency at 734 cm(-1) for AuF7 could not be verified
      computationally. It is concluded that the reported observation of AuF7 was
      probably erroneous. As the calculations indicate also an extremely large electron
      affinity and little stability for AuF6, Au(V) remains the highest well
      established gold oxidation state.

PMID- 16441135
TI  - Formation of higher chloride complexes of Np(IV) and Pu(IV) in water-stable room
      temperature ionic liquid [BuMeIm][Tf2N].
AB  - A UV/vis/near-IR spectroscopic study shows that in [BuMeIm][(CF3SO2)2N]
      hydrophobic room-temperature ionic liquid solutions, [BuMeIm]2[AnCl6] complexes,
      where BuMeIm+ is 1-n-butyl-3-methylimidazolium and An(IV) is Np(IV) or Pu(IV),
      have an octahedral An(IV) environment similar to that observed in solid
      complexes. Water has no influence on the absorption spectra of AnCl6(2-)
      complexes, indicating their stability to hydrolysis in ionic liquid. Adding
      [BuMeIm]Cl modifies the UV/vis/near-IR absorption spectra of An(IV) in the ionic
      liquid and causes solids to precipitate. The solid-state reflectance spectra of
      the precipitates reveal considerable differences from the corresponding An(IV)
      hexachloro complexes. A voltammetric study indicates that AnCl6(2-) complexes are
      electrochemically inert in [BuMeIm][(CF3SO2)2N] at the glassy carbon working
      electrode. By contrast, quasi-reversible electrochemical reduction An(IV)/An(III)
      and An(IV) oxidation are observed in ionic liquids in the presence of [BuMeIm]Cl.
      The oxidation wave of noncoordinated chloride ions interferes with the An(IV)
      oxidation waves. The spectroscopic and voltammetric data clearly indicate the
      formation of nonoctahedral actinide(IV) chloride complexes with a Cl-/An(IV)
      ratio exceeding 6/1 in [BuMeIm][(CF3SO2)2N] in excess chloride ions.

PMID- 16441136
TI  - Structural and texture evolution with temperature of layered double hydroxides
      intercalated with paramolybdate anions.
AB  - Paramolybdate-LDHs with MgAl or ZnAl cations within the layers have been prepared
      by the ion-exchange method from hydrotalcites with different interlayer anions
      (OH-, NO3(-), and terephthalate). The samples and the oxides obtained after their
      calcination were characterized by element chemical analysis, PXRD, FT-Raman
      spectroscopy, thermal analysis (TG/DTA), N2 adsorption at -196 degrees C, and
      SEM. The results show that layered solids with hydrotalcite-type structure were
      obtained in which the interlayer space is occupied by heptamolybdate with a small
      amount of MoO4(2-) units formed through hydrolysis of the polyanion; both
      oxomolybdenum species undergo a progressive distortion of the octahedral units
      from 50 degrees C but are roughly stable up to 250 degrees C as a consequence of
      the interaction between the polyanion and the brucite-like layers. This
      distortion is responsible for the observed decrease in the height of the gallery
      for samples heated in the temperature range, 50-250 degrees C, with respect to
      the original samples. Rehydration of the calcined solids allows recovering of
      their original structures and the initial values for the gallery heights.
      Calcination between 300 and 400 degrees C gives rise to a collapse of the layered
      structure, and amorphous phases are formed, in which molybdenum is both
      octahedrally and tetrahedrally coordinated. Crystalline magnesium and zinc
      molybdates (MgMoO4 and ZnMoO4) are formed at 450 and 600 degrees C, respectively.
      All solids have some microporosity, which decreases with increasing the
      calcination temperature.

PMID- 16441137
TI  - Rhodium assisted C-H activation of benzaldehyde thiosemicarbazones and their
      oxidation via activation of molecular oxygen.
AB  - The benzaldehyde thiosemicarbazones are found to undergo oxidation at the sulfur
      center upon reaction with [Rh(PPh3)3Cl] in refluxing ethanol in the presence of a
      base (NEt3). A group of organorhodium complexes are obtained from such reactions,
      in which the oxidized thiosemicarbazones are coordinated to rhodium as tridentate
      CNS donors, along with two triphenylphosphines and a hydride. From the reaction
      with para-nitrobenzaldehyde thiosemicarbazone, a second organometallic complex is
      obtained, in which the thiosemicarbazone is coordinated to rhodium as a
      tridentate CNS donor, along with two triphenylphosphines and a hydride. Reaction
      of the benzaldehyde thiosemicarbazones with [Rh(PPh3)3Cl] in refluxing ethanol in
      the absence of NEt3 affords another group of organorhodium complexes, in which
      the thiosemicarbazones are coordinated to rhodium as tridentate CNS donors, along
      with two triphenylphosphines and a chloride. Structures of representative
      complexes of each type of complexes have been determined by X-ray
      crystallography. In all of the complexes, the two PPh3 ligands are trans. All of
      the complexes show intense MLCT transitions in the visible region. Cyclic
      voltammetry on these complexes shows a Rh(III)-Rh(IV) oxidation on the positive
      side of SCE. Redox responses of the coordinated thiosemicarbazones are also
      displayed by all of the complexes.

PMID- 16441138
TI  - Dioxo- and oxovanadium(V) complexes of thiohydrazone ONS donor ligands:
      synthesis, characterization, reactivity, and antiamoebic activity.
AB  - As a contribution to the development of novel vanadium complexes with
      pharmacologically interesting properties, two neutral dioxovanadium(V) complexes
      [VO2(Hpydx-sbdt)] (1) and [VO2(Hpydx-smdt)] (3) [H2pydx-sbdt (I) and H2pydx-smdt
      (II) are the Schiff bases derived from pyridoxal and S-benzyl- or S
      methyldithiocarbazate] have been synthesized by the reaction of [VO(acac)2] and
      the potassium salts of the ligands in methanol followed by aerial oxidation.
      Heating of the methanolic solutions of these complexes yields the oxo-bridged
      binuclear complexes [{VO(pydx-sbdt)}2mu-O] (2) and [{VO(pydx-smdt)}2mu-O] (4).
      The crystals and molecular structures of 1, 3 x 1.5H2O, and 4 x 2CH3OH have been
      determined, confirming the ONS binding mode of the dianionic ligands in their
      thioenolate form. The ring nitrogen of the pyridoxal moiety is protonated in
      complexes 1 and 3. Acidification of 1 and 3 with HCl dissolved in methanol
      afforded oxohydroxo complexes, while in a methanolic KOH solution, the
      corresponding dioxo species K[VO2(pydx-sbdt/smdt)] are formed. Treatment of 1 and
      3 with H2O2 yields (unstable) oxoperoxovanadium(V) complexes, the formation of
      which has been established spectrophotometrically. In vitro antiamoebic
      activities (against HM1:1MSS strain of Entamoeba histolytica) were established
      for all of the dioxo- and oxovanadium(V) complexes. The complexes 1, 2, and 4
      were more effective than metronidazole, a commonly used drug against amoebiasis,
      suggesting that oxovanadium(V) complexes derived from thiohydrazones may open a
      new dimension in the therapy of amoebiasis.

PMID- 16441139
TI  - Insight into framework destruction in ultramarine pigments.
AB  - We report key evidence on the framework destruction in ultramarine pigments upon
      color fading. Experiments on faded pigments in a fresco painting environment
      reveal that the paramagnetic chromophores are set free via sodalite framework
      destruction and are subsequently degraded. Fading in acidic media produces
      similar results, although a larger number of beta-cages appear to be destroyed,
      and H2S is released. The findings are further supported by studies on natural and
      synthetic ultramarine pigments of various shades via solid-state resonance-Raman
      spectroscopy, colorimentry, and solid-state 29Si and 27Al NMR spectroscopy. NMR
      parameters are shown to correlate well with the intensities of Raman signals
      corresponding to the S3(-*) chromophores. A further correlation is established
      between the colorimetric parameters, L* (lightness) and C* (chroma), and the
      paramagnetic shift and paramagnetic linebroadening in NMR spectra for both 27Al
      and 29Si.

PMID- 16441141
TI  - Synthesis, characterization, and DNA binding of new water-soluble
      cyclopentadienyl ruthenium(II) complexes incorporating phosphines.
AB  - The new water-soluble ruthenium(II) chiral complexes [RuCpX(L)(L')](n+) (X = Cl,
      I. L = PPh3; L' = PTA, mPTA; L = L' = PTA, mPTA) (PTA = 1,3,5-triaza-7
      phosphaadamantane; mPTA = N-methyl-1,3,5-triaza-7-phosphaadamantane) have been
      synthesized and characterized by NMR and IR spectroscopy and elemental analysis.
      The salt mPTA(OSO2CF3) was also prepared and fully characterized by spectroscopic
      techniques. X-ray crystal structures of [RuClCp(PPh3)(PTA)] (2),
      [RuCpI(PPh3)(PTA)] (3), and [RuCpI(mPTA)(PPh3)](OSO2CF3) (9) have been
      determined. The binding properties toward DNA of the new hydrosoluble complexes
      have been studied using the mobility shift assay. The ruthenium chloride
      complexes interact with DNA depending on the hydrosoluble phosphine bonded to the
      metal, while the corresponding compounds with iodide, [RuCpI(PTA)2] (1),
      [RuCpI(PPh3)(PTA)] (3), [RuCpI(mPTA)2](OSO2CF3)2 (6), and
      [RuCpI(mPTA)(PPh3)](OSO2CF3) (9), do not bind to DNA.

PMID- 16441140
TI  - Mono-, di-, and oligonuclear complexes of Cu(II) ions and p-hydroquinone ligands:
      syntheses, electrochemical properties, and magnetic behavior.
AB  - Four highly soluble square-planar Cu(II) and Ni(II) complexes of siloxy-salens
      (2SiCu, 2SiNi) and hydroxy-salens (2Cu, 2Ni) have been synthesized. An X-ray
      crystal structure analysis was performed on 2SiCu, 2SiNi, and 2Ni. The compounds
      have been investigated by cyclic voltammetry, UV-vis-NIR spectroelectrochemistry,
      and EPR spectroscopy. According to these results, the monooxidized species
      [2SiCu]+ and [2SiNi]+ are to be classified as Robin-Day class II and III systems,
      respectively. Magnetic measurements on the dinuclear (PMDTA)Cu(II) complex 1Cu2 x
      (PF6)2 with deprotonated 1,4-dihydroxy-2,5-bis(pyrazol-1-yl)-benzene (1) linker
      revealed antiferromagnetic coupling between the two Cu(II) ions thereby resulting
      in an isolated dimer compound. Coordination polymers [1Cu]n(H2O)(2n) of Cu(II)
      ions and bridging p-hydroquinone linkers were obtained from CuSO4 x 5 H2O and 1,4
      dihydroxy-2,5-bis(pyrazol-1-yl)benzene. X-ray crystallography revealed linear
      chains running along the crystallographic a-direction and stacked along the b
      axis. Within these chains, the Cu(II) ions are coordinated by two pyrazolyl
      nitrogen atoms and two p-hydroquinone oxygen atoms in a square-planar fashion.

PMID- 16441142
TI  - Static magnetic-field-induced phase lag in the magnetization response of
      tris(dipicolinato)lanthanides.
AB  - Alternating-current (ac) magnetic susceptibility measurements for
      tris(dipicolinato) complexes with a trivalent heavy lanthanide ion,
      [N(C2H5)4]3[Ln(dipic)(3)] x nH2O (dipic = pyridine-2,6-dicarboxylate; Ln = Tb,
      Dy, Ho, Er, Tm, or Yb) are reported. While none of the six complexes showed a
      magnetization lag from the ac magnetic field of 10-10(3) Hz above 1.8 K, the Dy,
      Er, and Yb complexes with odd numbers of 4f electrons exhibited the magnetization
      lag in a static magnetic field. This phenomenon is explained to be caused by the
      elimination of a fast relaxation path, which is only effective for the Kramers
      doublet ground states in near zero field. At higher static fields, the remaining
      paths such as Orbach and/or direct processes govern the dynamics of the two-level
      systems comprised of spin-up and spin-down states. The non-Kramers complexes were
      found to have a nondegenerate ground state with large energy gaps from higher
      states, which is consistent with their fast magnetization relaxation.

PMID- 16441143
TI  - Chemistry and electrochemistry of the heterodinuclear complex ClPd(dppm)2PtCl: a
      M-M' bond providing site selectivity.
AB  - The heterodinuclear d(9)-d(9) title compound 1, whose crystal structure has been
      solved, reacts with dppm [bis(diphenylphosphino)methane] in the presence of NaBF4
      to generate the salt [ClPd(mu-dppm)2Pt(eta(1)-dppm)][BF4] (2a), which contains a
      Pt-bound dangling dppm ligand. 2a has been characterized by 1H and 31P NMR,
      Fourier transform Raman [nu(Pd-Pt) = 138 cm(-1)], and UV-vis spectroscopy
      [lambda(max)(dsigma-dsigma*) = 366 nm]. In a similar manner, [ClPd(mu
      dppm)2Pt(eta(1)-dppm=O)][BF4] (2b), ligated with a dangling phosphine oxide, has
      been prepared by the addition of dppm=O. The molecular structure of 2b has been
      established by an X-ray diffraction study. 2a reacts with 1 equiv of NaBH4 to
      form the platinum hydride complex [(eta(1)-dppm)Pd(mu-dppm)2Pt(H)][BF4] (3). Both
      2a and 3 react with an excess of NaBH4 to provide the mixed-metal d(10)-d(10)
      compound [Pd(mu-dppm)3Pt] (4). The photophysical properties of 4 were studied by
      UV-vis spectroscopy [lambda(max)(dsigma-dsigma*) = 460 nm] and luminescence
      spectroscopy (lambda(emi) = 724 nm; tau(e) = 12 +/- 1 micros, 77 K). The
      protonation of 1 and 4 leads to [ClPd(mu-dppm)2(mu-H)PtCl]+ (5) and 3,
      respectively. Stoichiometric treatment of 1 with cyclohexyl or xylyl isocyanide
      yields [ClPd(mu-dppm)2Pt(CNC6H11)]Cl (6a) and [ClPd(mu-dppm)2Pt(CN-xylyl)]Cl (6b)
      ligated by terminal-bound CNR ligands. In contrast, treatment of 1 with the
      phosphonium salt [C[triple bond]NCH2PPh3]Cl affords the structurally
      characterized A-frame compound [ClPd(mu-dppm)2(mu-C=NCH2PPh3)PtCl]Cl (6c),
      spanned by a bridging isocyanide ligand. The electrochemical reduction of 2a at 
      1.2 V vs SCE, as well as the reduction of 5 in the presence of dppm, leads to a
      mixture of products 3 and 4. Further reduction of 3 at -1.7 V vs SCE generates 4
      quantitatively. The reoxidation at 0 V of 4 in the presence of Cl- ions produces
      back complex 2a. The whole mechanism of the reduction of 1 has been established.

PMID- 16441144
TI  - Metal-induced reductive ring opening of 1,2,4,5-tetrazines: three resulting
      coordination alternatives, including the new non-innocent 1,2-diiminohydrazido(2
      ) bridging ligand system.
AB  - Reaction of 3,6-diaryl-1,2,4,5-tetrazines (aryl = R = phenyl, 2-furyl or 2
      thienyl) with 2 equiv of Ru(acac)2(CH3CN)2 results in reductive tetrazine ring
      opening to yield diruthenium complexes [(acac)2Ru(III)(dih-R(2-))Ru(III)(acac)2]
      bridged by the new 1,2-diiminohydrazido(2-) (dih-R(2-) = HNC(R)NNC(R)NH(2-))
      ligands. rac/meso diastereoisomers could be detected and separated for the
      compounds with R = phenyl and 2-thienyl, all species are diamagnetic and were
      characterized by 1H NMR spectroscopy. Crystal structure determination of the meso
      isomers with R = phenyl and 2-thienyl confirmed the 1,2-diiminohydrazido
      formulation through long N-N (approximately 1.40 A) and short C=N(H) bonds
      (approximately 1.31 A), implying two bridged ruthenium(III) centers at about
      4.765 A distance with strong antiferromagnetic coupling. The complexes undergo
      two reversible and well-separated one-electron reduction and oxidation processes,
      respectively. EPR Spectroscopy of the paramagnetic intermediates with
      comproportionation constants K(c) > 10(12) and UV-vis-NIR spectroelectrochemistry
      were used to identify the accessible redox states as [(acac)2Ru(II)(dih-R(2
      ))Ru(II)(acac)2]2-, [(acac)2Ru(II)(dih-R(*-))Ru(II)(acac)2]-, [(acac)2Ru(III)(dih
      R(2-))Ru(III)(acac)2], [(acac)2Ru(III)(dih-R(*-))Ru(III)(acac)2]+, and
      [(acac)2Ru(III)(dih-R)Ru(III)(acac)2]2+. While the UV-vis-NIR spectroscopic
      response of [(acac)2Ru(dih-R)Ru(acac)2](0/-/2-) is very similar to that of
      [(bpy)2Ru(adc-R)Ru(bpy)2](4+/3+/2+), adc-R(2-) = 1,2-diacylhydrazido(2-), the EPR
      result indicating ligand-centered spin for [(acac)2Ru(II)(dih-R(*
      ))Ru(II)(acac)2]- despite deceptive NIR absorptions around 1400 nm reveals
      distinct differences in the electronic structures.

PMID- 16441145
TI  - A comparative mechanistic study of the reversible binding of NO to a water
      soluble octa-cationic Fe(III) porphyrin complex.
AB  - The water-soluble, non-mu-oxo dimer-forming porphyrin, [5,10,15,20-tetrakis-4'-t
      butylphenyl-2',6'-bis-(N-methylene-(4''-t-butylpyridinium))porphyrinato]iron(III)
      octabromide, (P(8+))Fe(III), with eight positively charged substituents in the
      ortho positions of the phenyl rings, was characterized by UV-vis and 1H NMR
      spectroscopy and 17O NMR water-exchange studies in aqueous solution.
      Spectrophotometric titrations of (P(8+))Fe(III) indicated a pKa1 value of 5.0 for
      coordinated water in (P(8+))Fe(III)(H2O)2. The monohydroxo-ligated
      (P(8+))Fe(III)(OH)(H2O) formed at 5 < pH < 12 has a weakly bound water molecule
      that undergoes an exchange reaction, k(ex) = 2.4 x 10(6) s(-1), significantly
      faster than water exchange on (P(8+))Fe(III)(H2O)2, viz. k(ex) = 5.5 x 10(4) s(
      1) at 25 degrees C. The porphyrin complex reacts with nitric oxide to yield the
      nitrosyl adduct, (P(8+))Fe(II)(NO+)(L) (L = H2O or OH-). The diaqua-ligated
      (P(8+))Fe(III)(H2O)2 binds and releases NO according to a dissociatively
      activated mechanism, analogous to that reported earlier for other
      (P)Fe(III)(H2O)2 complexes. Coordination of NO to (P(8+))Fe(III)(OH)(H2O) at high
      pH follows an associative mode, as evidenced by negative deltaS(double
      dagger)(on) and deltaV(double dagger)(on) values measured for this reaction. The
      observed ca. 10-fold decrease in the NO binding rate on going from six-coordinate
      (P(8+))Fe(III)(H2O)2 (k(on) = 15.1 x 10(3) M(-1) s(-1)) to
      (P(8+))Fe(III)(OH)(H2O) (k(on) = 1.56 x 10(3) M(-1) s(-1) at 25 degrees C) is
      ascribed to the different nature of the rate-limiting step for NO binding at low
      and high pH, respectively. The results are compared with data reported for other
      water-soluble iron(III) porphyrins with positively and negatively charged meso
      substituents. Influence of the porphyrin periphery on the dynamics of reversible
      NO binding to these (P)Fe(III) complexes as a function of pH is discussed on the
      basis of available experimental data.

PMID- 16441147
TI  - Syntheses, structural determinations of [Ru(ROCS2)2(PPh3)2](+/0) pairs, and
      kinetic analyses of thermal reactions involving transient trans
      [Ru(iPrOCS2)2(PPh3)2] species (ROCS2(-) = ethyl- or isopropyldithiocarbonate and
      PPh3 = triphenylphosphine).
AB  - Controlled-potential electrochemical oxidation of cis-[Ru(ROCS2)2(PPh3)2] (R =
      Et, iPr) yielded corresponding Ru(III) complexes, and the crystal structures of
      cis-[Ru(ROCS2)2(PPh3)2] and trans-[Ru(ROCS2)2(PPh3)2](PF6) were determined. Both
      pairs of complexes exhibited almost identical coordination structures. The Ru-P
      distances in trans-[Ru(III)(ROCS2)2(PPh3)2](PF6) [2.436(3)-2.443(3) A] were
      significantly longer than those in cis-[Ru(II)(ROCS2)2(PPh3)2] [2.306(1)-2.315(2)
      A]: the smaller ionic radius of Ru(III) than that of Ru(II) stabilizes the trans
      conformation for the Ru(III) complex due to the steric requirement of bulky
      phosphine ligands while mutual trans influence by the phosphine ligands induces
      significant elongation of the Ru(III)-P bonds. Cyclic voltammograms of the cis
      [Ru(ROCS2)2(PPh3)2] and trans-[Ru(ROCS2)2(PPh3)2]+ complexes in dichloromethane
      solution exhibited typical dual redox signals corresponding to the cis
      [Ru(ROCS2)2(PPh3)2](+/0) (ca. +0.15 and +0.10 V vs ferrocenium/ferrocene couple
      for R = Et and iPr, respectively) and to trans-[Ru(ROCS2)2(PPh3)2](+/0) (-0.05
      and -0.15 V vs ferrocenium/ferrocene for R = Et and iPr, respectively) couples.
      Analyses on the basis of the Nicholson and Shain's method revealed that the
      thermal disappearance rate of transient trans-[Ru(ROCS2)2(PPh3)2] was dependent
      on the concentration of PPh3 in the bulk: the rate constant for the
      intramolecular isomerization reaction of trans-[Ru(iPrOCS2)2(PPh3)2] was
      determined as 0.338 +/- 0.004 s(-1) at 298.3 K (deltaH* = 41.8 +/- 1.5 kJ mol(-1)
      and deltaS* = -114 +/- 7 J mol(-1) K(-1)), while the dissociation rate constant
      of coordinated PPh3 from the trans-[Ru(iPrOCS2)2(PPh3)2] species was estimated as
      0.113 +/- 0.008 s(-1) at 298.3 K (deltaH* = 97.6 +/- 0.8 kJ mol(-1) and deltaS* =
      64 +/- 3 J mol(-1) K(-1)), by monitoring the EC reaction (electrode reaction
      followed by chemical processes) at different concentrations of PPh3 in the bulk.
      It was found that the trans to cis isomerization reaction takes place via the
      partial dissociation of iPrOCS2(-) from Ru(II), contrary to the previous claim
      that it takes place by the twist mechanism.

PMID- 16441146
TI  - O2 and CO binding to tetraaza-tripodal-capped iron(II) porphyrins.
AB  - A series of tris(2-aminoethylamine) (tren) capped iron(II) porphyrins has been
      synthesized and characterized and their affinities for dioxygen and carbon
      monoxide measured. The X-ray structure of the basic scaffold with nickel inserted
      in the porphyrin is also reported. All the ligands differ by the nature of the
      group(s) attached to the secondary amine functions of the cap. These various
      substitutions were introduced to probe if a hydrogen bond with these secondary
      amine groups acting as the donor could rationalize the high affinity of these
      myoglobin models. This work clearly indicates that the cage structure of the tren
      predominates over all the other appended groups with the exception of p
      nitrophenol.

PMID- 16441148
TI  - Systematic DFT study of gas phase and solvated uranyl and neptunyl complexes
      [AnO2X4]n (An = U, Np; X = F, Cl, OH, n = -2; X = H2O, n = +2).
AB  - The six-valent uranyl and neptunyl complexes [An(VI)O2X4]n (An = U, Np; X = F,
      Cl, OH, n = -2; X = H2O, n = +2) have been studied within the framework of
      density functional theory. The relative stabilities of the cis and trans isomers,
      structural properties, charge distribution, and ligand binding energies have been
      determined using the modified Perdew-Burke-Ernzerhof functional at the all
      electron scalar relativistic level. Uranyl and neptunyl complexes with different
      ligands have been compared in a systematic fashion, demonstrating close
      similarity of these actinides in oxidation state VI. In addition, the effect of
      an aqueous solution has been taken into account with the polarizable continuum
      model COSMO. Computed averaged ligand binding energies permit one to rationalize
      the observed different stabilities of the title species in aqueous media.

PMID- 16441149
TI  - Reactivity of aquacobalamin and reduced cobalamin toward S-nitrosoglutathione and
      S-nitroso-N-acetylpenicillamine.
AB  - The reactions of aquacobalamin (Cbl(III)H2O, vitamin B12a) and reduced cobalamin
      (Cbl(II), vitamin B12r) with the nitrosothiols S-nitrosoglutathione (GSNO) and S
      nitroso-N-acetylpenicillamine (SNAP) were studied in aqueous solution at pH 7.4.
      UV-vis and NMR spectroscopic studies and semiquantitative kinetic investigations
      indicated complex reactivity patterns for the studied reactions. The detailed
      reaction routes depend on the oxidation state of the cobalt center in cobalamin,
      as well as on the structure of the nitrosothiol. Reactions of aquacobalamin with
      GSNO and SNAP involve initial formation of Cbl(III)-RSNO adducts followed by
      nitrosothiol decomposition via heterolytic S-NO bond cleavage. Formation of
      Cbl(III)(NO-) as the main cobalamin product indicates that the latter step leads
      to efficient transfer of the NO- group to the Co(III) center with concomitant
      oxidation of the nitrosothiol. Considerably faster reactions with Cbl(II) proceed
      through initial Cbl(II)-RSNO intermediates, which undergo subsequent electron
      transfer processes leading to oxidation of the cobalt center and reduction of the
      nitrosothiol. In the case of GSNO, the overall reaction is fast (k approximately
      1.2 x 10(6) M(-1) s(-1)) and leads to formation of glutathionylcobalamin
      (Cbl(III)SG) and nitrosylcobalamin (Cbl(III)(NO-)) as the final cobalamin
      products. A mechanism involving the reversible equilibrium Cbl(II) + RSNO <==>
      Cbl(III)SR + NO is suggested for the reaction on the basis of the obtained
      kinetic and mechanistic information. The corresponding reaction with SNAP is
      considerably slower and occurs in two distinct reaction steps, which result in
      the formation of Cbl(III)(NO-) as the ultimate cobalamin product. The
      significantly different kinetic and mechanistic features observed for the
      reaction of GSNO and SNAP illustrate the important influence of the nitrosothiol
      structure on its reactivity toward metal centers of biomolecules. The potential
      biological implications of the results are briefly discussed.

PMID- 16441150
TI  - Titanium(II) and titanium(III) tetrahydroborates. Crystal structures of
      [Li(Et2O)2][Ti2(BH4)5(PMe2Ph)4], Ti(BH4)3(PMe2Ph)2, and Ti(BH4)3(PEt3)2.
AB  - The molecular structures of the titanium(III) borohydride complexes
      Ti(BH4)3(PEt3)2 and Ti(BH4)3(PMe2Ph)2 have been determined. If the BH4 groups are
      considered to occupy one coordination site, both complexes adopt distorted
      trigonal bipyramidal structures with the phosphines in the axial sites; the P-Ti
      P angles deviate significantly from linearity and are near 156 degrees. In both
      compounds, two of the three BH4 groups are bidentate and one is tridentate. The
      deduced structures differ from the one previously described for the PMe3 analogue
      Ti(BH4)3(PMe3)2, in which two of the tetrahydroborate groups were thought to be
      bound to the metal in an unusual "side-on" (eta(2)-B,H) fashion. Because the
      PMe3, PEt3, and PMe2Ph complexes have nearly identical IR spectra, they most
      likely have similar structures. The current evidence strongly suggests that the
      earlier crystal structure of Ti(BH4)3(PMe3)2 was incorrectly interpreted and that
      these complexes all adopt structures in which two of the BH4 groups are bidentate
      and one is tridentate. The synthesis of the titanium(III) complex
      Ti(BH4)3(PMe2Ph)2 affords small amounts of a second product: the titanium(II)
      complex [Li(Et2O)2][Ti2(BH4)5(PMe2Ph)4]. The [Ti2(BH4)5(PMe2Ph)4]- anion consists
      of two Ti(eta(2)-BH4)2(PMe2Ph)2 centers linked by a bridging eta(2),eta(2)-BH4
      group that forms a Ti...(mu-B)...Ti angle of 169.9(3) degrees. Unlike the
      distorted trigonal bipyramidal geometries seen for the titanium(III) complexes,
      the metal centers in this titanium(II) species each adopt nearly ideal tbp
      geometries with P-Ti-P angles of 172-176 degrees. All three BH4 groups around
      each Ti atom are bidentate. One of the BH4 groups on each Ti center bridges
      between Ti and an ether-coordinated Li cation, again in an eta(2),eta(2) fashion.
      The relationships between the electronic structures and the molecular structures
      of all these titanium complexes are briefly discussed.

PMID- 16441152
TI  - cis-to-trans isomerization promoted by pyridine as a crucial step for the
      selective preparation of trans-Pt(SAr)(Cl)(PAr'3)2.
AB  - The general strategy for the syntheses of trans-Pt(SAr)(Cl)(PAr'3)2 (1) (Ar = Ph,
      C6H4-2-Me, C6H4-3-OMe C6H4-2-F, etc.; Ar' = Ph, C6H4-4-OMe, C6H4-4-Me, and C6H4-4
      CF3) by the reaction of cis-PtCl2(PAr'3)2 with ArSH has been developed. The
      mechanistic investigation suggested that isomerization of cis-1 into trans-1
      promoted by the combined use of C6H6 as a solvent and pyridine as a base was the
      key to the successful preparation of 1.

PMID- 16441151
TI  - Production and reactions of organic-soluble lanthanide complexes of the
      monolacunary Dawson [alpha1-P2W17O61]10- polyoxotungstate.
AB  - The incorporation of lanthanides into polyoxometalates provides entry to new
      classes of potentially useful materials that combine the intrinsic properties of
      both constituents. To utilize the [alpha1-Ln(H2O)4P2W17O61]7- species in
      applications of catalysis and development of luminescent materials, the chemistry
      of this family of lanthanide polyoxometalates in organic solvents has been
      developed. Organic-soluble polyoxometalate-lanthanide complexes TBA5H2[alpha1
      Ln(H2O)4P2W17O61] (Ln = La(III), Sm(III), Eu(III), Yb(III)) were prepared and
      characterized by elemental analysis, acid-base titration, IR, 31P NMR, and mass
      spectrometry. The synthetic procedure involves a cation metathesis reaction in
      aqueous solution under strict pH control. A solid-liquid-phase transfer protocol
      yielded a unique species (TBA)8K3[Yb(alpha1-YbP2W17O61)2] with three ytterbium
      ions and two [alpha1-P2W17O61]10- polyoxotungstates. A centrosymmetric dimeric
      complex [{alpha1-La(H2O)4P2W17O61}2]14- was crystallized from aqueous solution
      and characterized by X-ray diffraction. ESI mass spectral analysis of the
      complexes TBA5H2[alpha1-Ln(H2O)4P2W17O61] shows that similar dimers exist in
      organic solution, in particular for the early lanthanides. Fragmentation in the
      mass spectrometer of the complexes from dry acetonitrile solution involves double
      protonation of an oxo ligand and loss of one water molecule. Low mass tungstate
      fragments combine into [(WO3)n]2- (n = 1-5) ions and their condensation products
      with phosphate. Reaction of TBA5H2[alpha1-Eu(H2O)4P2W17O61] with 1,10
      phenanthroline or 2,2'-bipyridine showed an increase of the europium
      luminescence. This result is explained by the formation of a ternary complex of
      [alpha1-Eu(H2O)4P2W17O61]7- and two sensitizing ligands.

PMID- 16441153
TI  - Nanoparticles for biotechnology applications.

PMID- 16441154
TI  - Comparison of DNA detection methods using nanoparticles and silver enhancement.
AB  - DNA microarrays are an emerging technology for the parallel detection of DNA
      molecules. Fluorescent molecules are the current standard for a DNA array's
      optical readout but they possess some drawbacks including the stability of the
      dyes and the cost of the scanners. Therefore alternative labelling strategies are
      of considerable interests. One such strategy is the use of nanoparticles which
      offers several advantages in terms of stability and versatility of the detection
      mode. The authors present a review on the different ways DNA can be detected,
      mainly onto a solid support, using nanoparticle labels.

PMID- 16441155
TI  - Biological applications of localised surface plasmonic phenomenae.
AB  - Researchers and industrialists have taken advantage of the unusual optical,
      magnetic, electronic, catalytic, and mechanical properties of nanomaterials.
      Nanoparticles and nanoscale materials have proven to be useful for biological
      uses. Nanoscale materials hold a particular interest to those in the biological
      sciences because they are on the same size scale as biological macromolecules,
      proteins and nucleic acids. The interactions between biomolecules and
      nanomaterials have formed the basis for a number of applications including
      detection, biosensing, cellular and in situ hybridisation labelling, cell tagging
      and sorting, point-of-care diagnostics, kinetic and binding studies, imaging
      enhancers, and even as potential therapeutic agents. Noble metal nanoparticles
      are especially interesting because of their unusual optical properties which
      arise from their ability to support surface plasmons. In this review the authors
      focus on biological applications and technologies that utilise two types of
      related plasmonic phenomonae: localised surface plasmon resonance (LSPR)
      spectroscopy and surface-enhanced Raman spectroscopy (SERS). The background
      necessary to understand the application of LSPR and SERS to biological problems
      is presented and illustrative examples of resonant Rayleigh scattering,
      refractive index sensing, and SERS-based detection and labelling are discussed.

PMID- 16441156
TI  - Use of magnetic nanoparticle heating in the treatment of breast cancer.
AB  - Magnetic nanoparticles are promising tools for the minimal invasive elimination
      of small tumours in the breast using magnetically-induced heating. The approach
      complies with the increasing demand for breast conserving therapies and has the
      advantage of offering a selective and refined tuning of the degree of energy
      deposition allowing an adequate temperature control at the target. The
      biophysical basis of the approach, the magnetic and structural properties of
      magnetic nanoparticles are reviewed. Results with model targets and in vivo
      experiments in laboratory animals are reported.

PMID- 16441157
TI  - Magnetic particles as markers and carriers of biomolecules.
AB  - The detection and manipulation of biomolecules on a common platform is of
      considerable interest not only for application in devices such as diagnostic
      tools but also for basic research in biological and medical systems. A promising
      approach is the utilisation of magnetic particles as markers and carriers for
      biomolecules. The principle functionality of this approach is demonstrated by the
      authors. Magnetic particles used as markers can be detected by highly sensitive
      magnetoresistive sensors resulting in a purely electronic signal. A direct
      comparison with the standard fluorescence method reveals the advantages of using
      the magnetic particles. In addition, magnetic particles used as carriers can be
      manipulated on-chip via currents running through especially designed line
      patterns. Some current drawbacks and future aspects are discussed. The
      combination of sensing and manipulating magnetic particles is a promising choice
      for future integrated lab-on-a-chip systems.

PMID- 16441158
TI  - Chip-based electrical detection of DNA.
AB  - A variety of methods have been developed for the detection of the binding of the
      complementary strand of DNA to a gene chip using electrical rather than the
      established optical signal techniques. Chip-based DNA sensors offer sensitivity,
      specificity, parallelisation and miniaturisation for the detection of selected
      DNA sequences or mutated genes associated with human diseases. Problems
      associated with the established fluorescence-based optical detection technique
      include the high equipment costs and the need to use sophisticated numerical
      algorithms to interpret the data. These problems generally limit its use to
      research laboratories and make it hard to adapt this detection scheme for on-site
      or point-of-care use. An electrical readout might be a solution to these
      problems. A review of a number of different approaches to achieve an electrical
      readout for a DNA chip is presented. The review covers various methods that are
      based on the use of metal nanoparticles as labels and also electrochemical
      methods that use polymer-modified electrodes, DNA-specific redox reporters, and
      DNA-mediated charge transport techniques.

PMID- 16441159
TI  - Resonant nano-cluster devices.
AB  - The resonance-enhanced absorption (REA) by metal clusters on a surface is an
      effective technique on which to base bio-optical devices. A four-layer device
      consisting of a metal mirror, a polymer or glass-type distance layer, a
      biomolecule interaction layer and a sub-monolayer of biorecognitively bound metal
      nano-clusters is reported. Experiments indicate a strong influence of the
      resonator homogeneity on the absorption maximum. Layer stability plays an
      important role in the overall performance of the device. Techniques and optimised
      lab protocols to set up biochips that use the REA process in the detection are
      presented. The sensors show one to three narrow reflection minima in the visible
      and or infra-red (IR) part of the spectrum and therefore they do not suffer from
      the spectral limitations associated with spherical gold colloids. Metal clusters
      (synthesised by thermal step reduction) as well as metal- dielectric shell
      clusters (synthesised by various shell deposition processes) are used to
      precisely shift the readout of the device to any frequency in the visible and
      near IR range. Disposable single-step protein chips, DNA assays as well as
      complex biochip arrays are established that use various DNARNA, antigen-antibody
      and protein-protein interaction systems.

PMID- 16441160
TI  - Infrared up-converting phosphors for bioassays.
AB  - The development of up-converting phosphor reporter particles has added a powerful
      tool to modern detection technologies. Carefully constructed phosphor reporters
      have core-shell structures with surface functional groups suitable for standard
      bio-conjugations. These reporters are chemically stable, possess the unique
      property of infrared up-conversion, and are readily detected. In contrast to
      conventional fluorescent reporters, up-converting phosphor particles do not
      bleach and allow permanent excitation with simultaneous signal integration. A
      large anti-Stokes shift (up to 500 nm) separates discrete emission peaks from the
      infrared excitation source. Along with the unmatched contrast in biological
      specimens due to the absence of autofluorescence upon infrared excitation, up
      converting phosphor technology (UPT) has unique properties for highly-sensitive
      particle-based assays. The production and characteristics of UPT reporter
      particles as well as their application in various bioassays is reviewed.

PMID- 16441161
TI  - Encapsulation in sub-micron species: a short review and alternate strategy for
      dye encapsulation.
AB  - The encapsulation of molecular species has received considerable attention in
      recent years. Polymers, dendrimers and microemulsions along with other systems
      have been used as precursors for the synthesis of encapsulating agents.
      Especially important in this field is the core-shell architecture. This structure
      offers the encapsulated species an extra level of protection due to the presence
      of a shell, covering the interior of a capsule. Dyes, porphyrines, drugs, cells
      and other active agents have been successfully encapsulated, and the host-guest
      interaction has been studied by various experimental techniques. A review is new
      provided of the progress made in this field in the last several years is
      presented. Different classes of synthetic approaches are presented and resulting
      encapsulation studies are summarised. An approach to the encapsulation of dansyl
      chloride dye in core-shell nanoparticles is also presented.

PMID- 16441162
TI  - Selective enzymatic cleavage of gold nanoparticle-labelled DNA on a microarray.
AB  - The use of the restriction enzyme EcoRI for the manipulation of double-stranded
      DNA on microarrays is introduced. Gold nanoparticles are attached to a microarray
      via base pairing between complementary DNA sequences on the array and on the
      particles. These particles could be detected by light scattering measurements
      following an enhancement step, in which silver islands were deposited on top of
      the gold particles. This deposition of silver could be completely suppressed if
      the particles were removed by enzymatic cleavage of their DNA linker molecules.
      This cleavage step critically depends on the presence of a specific enzyme
      recognition site.

PMID- 16441163
TI  - Ligand-installed PEGylated bionanosphere.
AB  - The synthesis of poly(ethylene glycol)-b-poly(2-N,N
      dimethylaminoethylmethacrylate) processing an acetal group at the PEG chain end
      (acetal-PEGPAMA) is reported. The obtained acetal-PEGPAMA block copolymer was
      found to reduce tetrachloroauric acid at room temperature to produce gold
      nanoparticles. The size of these nanoparticles was controllable in the range of 6
      to 13 nm by changing the initial Au3+: polymer ratio. In addition to the
      reduction of tetrachloroauric acid, acetal-PEGPAMA bonds on the surface of the
      obtained gold nanoparticles to improve their dispersion stability in an aqueous
      medium even at a salt concentration as high as two. Biotinyl-PEGPAMA-anchored
      gold nanoparticles undergo specific aggregation in the presence of streptavidin
      thereby revealing their promising utility as colloidal sensing systems for use in
      biological systems. Biotin-PEGPAMA can also be utilised for the preparation of a
      functionally PEGylated quantum dot (QD). When CdCl2 and Na2S were mixed in
      aqueous media in the presence of the biotin-PEGPAMA, a CdS QD with an
      approximately 5 nm size was prepared. The polyamine segment was anchored onto the
      surface of the formed CdS nanoparticle, whereas the PEG segment was tethered onto
      the surface to form a hydrophilic palisade, thus improving the dispersion
      stability in aqueous media even under a high salt concentration condition. An
      effective fluorescent resonance energy transfer (FRET) was observed by the
      specific interaction of the biotin-PEGPAMA stabilised CdS QD with TexasRed
      labelled streptavidin with the physiological ionic strength of 0.15 M. The extent
      of the energy transfer was in proportion to the concentration of the TexasRed
      streptavidin. This FRET system using the PEGylated CdS QD coupled with
      fluorescent-labelled protein can be utilised as a highly sensitive bioanalytical
      system.

PMID- 16441164
TI  - Gold-nanoparticle-assisted oligonucleotide immobilisation for improved DNA
      detection.
AB  - Colloidal gold nanoparticles are investigated as a potential scaffold for the
      assisted immobilisation of probe oligonucleotides on silicon surfaces. A
      preliminary study is devoted to the examination of the immobilisation of DNA
      modified gold nanoparticles as a function of time, concentration, salt and pH.
      The DNA-modified nanoparticles self-assembled onto solid surfaces in a three
      dimensional self-assembled architecture. The functionalised surfaces are
      evaluated in diagnostic assays, where their potential to improve the efficiency
      of the hybridisation reaction is tested. The system utilising DNA-modified
      nanoparticles produced an enhancement in the hybridisation efficiency and the
      sensitivity limit by a factor 10 to 100 as compared to a conventional DNA
      immobilisation system on a planar surface.

PMID- 16441165
TI  - Silica microspheres for biomolecular detection applications.
AB  - Microsphere-based biosensors have been attracting the attention of the photonics
      community due to their high sensitivity, selectivity and implementation.
      Microspheres, with their high quality-factor (Q-factor) morphology dependent
      resonances, are very sensitive to refractive index and size changes. The
      perturbation of the microsphere morphology dependent resonances can be used for
      the detection of biomolecules. Adsorption of different biomolecules on the
      surface of microspheres causes a change of effective size and refractive index
      leading to the shift of resonance wavelengths. A biosensor, based on this
      phenomenon, can detect a single molecule sensitively depending on the
      configuration that needs to be designed and optimised. Silica with a refractive
      index of 1.5, which is very close to that of bimolecular agents, is a suitable
      photonic material to use for biosensing applications. The transverse electric and
      transverse magnetic elastic scattering spectra at 90 degrees and 0 degrees are
      calculated at 1.55 microm with the associated shifts after adding a layer on it.
      90 degrees scattering is used to monitor the scattered signal, whereas 0 degrees
      scattering is used to monitor the transmission signal.

PMID- 16441166
TI  - Titania nanospheres from supercritical fluids.
AB  - Surfactant-coated amorphous titania nanospheres have been synthesised using
      templating 'water-in-supercritical carbon dioxide' emulsion droplets; the process
      represents a clean and controlled method for the manufacture of high-purity
      nanoparticles.

PMID- 16441167
TI  - Force-velocity relationship of single actin filament interacting with immobilised
      myosin measured by electromagnetic technique.
AB  - The effect of applying an external load to actin filaments moving in the in vitro
      motility assay is studied. Bead-tailed actin filaments were made by polymerising
      actin onto 2.8 microm diameter Dynabeads conjugated with gelsolin-G actin. These
      were introduced into a motility cell coated with 100 microg/ml rabbit fast
      skeletal myosin in the presence of ATP and 0.5% methylcellulose. The motility
      cell was inserted between the pole-pieces of an electromagnet and the fluorescent
      beads and filaments were observed. The force-current relationship of the
      electromagnet was determined from the velocity of free beads in viscous solution
      and Stokes' equation. The magnet produced up to 6 pN force on the Dynabeads at 1
      A. Many bead-tailed actin filaments stuck to the surface, but the beads that did
      move moved at the same speed as unloaded f-actin in the same cell. Bead-tailed
      filaments slowed down under an increasing magnetic load, eventually stalled and
      then slid backward under increasing load before detaching from the surface.
      Single-filament force-velocity curves were constructed and a stalling force of
      about 0.6 pN/mm of actin filament estimated.

PMID- 16441168
TI  - Subtractive chromatography for purification and recovery of nano-bioproducts.
AB  - A novel polymer-coated adsorbent (subtractive adsorbent) has been manufactured
      and evaluated for the recovery of nanoparticle bioproducts. The core principle
      was to coat inert macroporous polymers (e.g. agarose) upon adsorbent beads of
      varied ligands. Here BSA nanoparticles, with an average nanoparticle diameter 95
      nm, were fabricated and selected as feedstock for the demonstration of the
      principle. The adsorption of a mixture of fluorescently labelled BSA solution and
      BSA nanoparticles was investigated in a batch binding experiment upon polymer
      coated Streamline DEAE and visualised by laser scanning confocal microscopy. The
      mechanistic design of such adsorbents and their basic application for the
      recovery of target nano-bioproducts from complex feedstock is strongly indicated.

PMID- 16441169
TI  - On-chip high-speed sorting of micron-sized particles for high-throughput
      analysis.
AB  - A new design of particle sorting chip is presented. The device employs a
      dielectrophoretic gate that deflects particles into one of two microfluidic
      channels at high speed. The device operates by focussing particles into the
      central streamline of the main flow channel using dielectrophoretic focussing. At
      the sorting junction (T- or Y-junction) two sets of electrodes produce a small
      dielectrophoretic force that pushes the particle into one or other of the outlet
      channels, where they are carried under the pressure-driven fluid flow to the
      outlet. For a 40 microm wide and high channel, it is shown that 6 microm diameter
      particles can be deflected at a rate of 300/s. The principle of a fully automated
      sorting device is demonstrated by separating fluorescent from non-fluorescent
      latex beads.

PMID- 16441170
TI  - Dielectrophoresis of reverse phase emulsions.
AB  - Reverse miniemulsions, emulsions of droplets of size 200 nm-1 microm of a polar
      liquid dispersed in an apolar continuous liquid phase, exhibit strong
      electrokinetic responses in low-frequency electric fields. The electrokinetic
      behaviour of a reverse miniemulsion, previously developed for use as electronic
      paper, has been investigated under static and flow conditions, in uniform and non
      uniform electric fields. Results reveal that when using frequencies lower than 10
      Hz strong aggregation of the droplets occurs. In uniform electric fields, under
      static conditions, droplets reversibly aggregate into honeycomb-like or irregular
      aggregates. Under flow conditions, droplets aggregate into approximately
      equidistant streams. In non-uniform electric fields the droplets reversibly
      aggregate in high-field regions, and can be guided along regions of high field
      strength in a flow. The potential of the technique for the formation of
      structured materials is discussed.

PMID- 16441171
TI  - Controlling cell destruction using dielectrophoretic forces.
AB  - Measurements are reported of the main factors, namely the AC voltage frequency
      and magnitude, that were observed to influence the number of cells destroyed
      during dielectrophoresis (DEP) experiments on Jurkat T cells and HL60 leukemia
      cells. Microelectrodes of interdigitated and quadrupolar geometries were used. A
      field-frequency window has been identified that should be either avoided or
      utilised, depending on whether or not cell damage is to be minimised or is a
      desired objective. The width and location of this frequency window depends on the
      cell type, as defined by cell size, morphology and dielectric properties, and is
      bounded by two characteristic frequencies. These frequencies are the DEP cross
      over frequency, where a cell makes the transition from negative to positive DEP,
      and a frequency determined by the time constant that controls the frequency
      dependence of the field induced across the cell membrane. When operating in this
      frequency window, and for the microelectrode designs used in this work, cell
      destruction can be minimised by ensuring that cells are not directed by positive
      DEP to electrode edges where fields exceeding 30-40 kV/m are generated.
      Alternatively, this field-frequency window can be exploited to selectively
      destroy specific cell types in a cell mixture.

PMID- 16441172
TI  - Parallel measurements of drug actions on Erythrocytes by dielectrophoresis, using
      a three-dimensional electrode design.
AB  - A type of well-based assay that uses a laminated three-dimensional electrode
      design to characterise the effects of different drugs on red blood cells using
      dielectrophoresis is presented. The capability of the system to determine the
      effects of chemical agents on the electrophysiology of red blood cells is
      demonstrated using saponin and valinomycin as two examples of drugs that can
      penetrate the cell membrane and therefore change the dielectric properties of the
      cell. Light intensity changes are measured in the well over a period of time at
      various frequencies and the dielectric properties of the cells determined using
      an ellipsoidal multi-shell model. It is shown that the laminated electrode
      permits a high degree of automation and thus a high number of parallel
      experiments, which reduces both the time and effort needed to examine differences
      between populations of red blood cells. The technique is directly compatible with
      the industry-standard 1536 well-plate analysis technique.

PMID- 16441174
TI  - Towards nanomedicine with a supramolecular approach: a review.
AB  - A review dedicated mainly to the results obtained by the authors on the use of
      cyclodextrin (CD) derivatives on protein (enzyme) stabilization through covalent
      and non-covalent interactions (host-guest supramolecular interactions) is
      presented here. This latter procedure served to introduce a new method for enzyme
      immobilization on metallic surfaces that can be used to prepare biosensors and
      therapeutic nanodevices. The surfaces of gold (and silver) electrodes and
      nanoparticles were modified with sulphur-containing cyclodextrin derivatives. The
      protein (enzyme) was then supramolecularly immobilized on the modified surface
      when one or more of its bulky hydrophobic moieties was included into the CD
      cavity. The protein can also be modified with a typical CD guest, such as
      adamantane, to achieve a more stable immobilization. Different examples are
      presented, such as a biosensor based on monolayers of adamantane-modified
      cytochrome c and a bienzymatic nanodevice comprising gold nanoparticles
      stabilized with CD associated to catalase and superoxide dismutase modified with
      complementary host-guest residues. The possibilities of this new approach for the
      development of biosensors and therapeutic nanodevices are analyzed.

PMID- 16441176
TI  - Aqueous compatible polymers in bionanotechnology.
AB  - Core-shell molecularly imprinted particles (CS-MIPs) have been synthesised using
      the technique of emulsion polymerisation with caffeine and theophylline being
      used in the surface template polymerisation with ethylene glycol dimethacrylate
      and oleylphenyl hydrogen phosphate. A radiolabelling study with caffeine-8-14C
      showed that the template was completely located at the particle surface during
      polymerisation. Caffeine could be specifically bound to a caffeine-imprinted CS
      MIP to give a biphasic Scatchard binding curve, whereas the binding profile to a
      theophylline-imprinted CS-MIP was monophasic. The nanoparticles have the
      potential to be used in the molecular recognition of small molecules in a complex
      biological matrix. Water soluble highly-branched imidazole end-chain
      functionalised polymers of nanodimensions have also been synthesised via
      reversible addition-fragmentation chain transfer polymerisation. The polymers
      have lower critical solution temperatures which occur at sub-ambient temperatures
      and have proven useful in the affinity precipitation of proteins which are
      particularly temperature sensitive, e.g. the histidine-tagged protein fragment
      BRCA1. An overview of both of these areas of research is described outlining the
      diversity of these aqueous compatible polymers in molecular recognition processes
      at the nanoscale.

PMID- 16441175
TI  - Nano-encapsulation of protein using an enteric polymer as carrier.
AB  - In this preliminary work, an enteric polymer has been used for encapsulating
      bovine serum albumine (BSA) as a model protein drug. Poly (lactide-co- glycolide)
      has been commonly used for oral administration purposes as a polymer matrix, but
      in this case an enteric polymer was used effectively to protect the protein in a
      gastric environment. A modified water/oil/water technique was used to decrease
      the particle diameter, and transmission electron microscopy experiments showed
      that the average diameter of the nanoparticles obtained was below 100 nm. The
      spherical nature of the particles and their diameters strongly depend on the
      control of the process parameters. The encapsulation efficiency was 77% for
      sample B4, and protein release profiles for both samples B3 and B4 indicate that
      these systems possess controlled-release characteristics. Finally, as a result of
      electrophoresis (SDS-PAGE), the BSA was not chemically affected under
      encapsulation conditions.

PMID- 16441177
TI  - Self-association behaviour of protein:surfactant systems in alcohol/water
      mixtures.
AB  - The effect of the addition of short-chain monohydric alcohols (ethanol and propan
      2-ol) to the protein:surfactant system lysozyme:sodium dodecyl sulfate (Lz:SDS)
      in aqueous solution was investigated using a conductometric technique. A second
      protein:surfactant system, bovine serum albumin:SDS (BSA:SDS) was also
      investigated so that the effect of a different protein conformation and
      composition could be compared. The critical aggregation concentration (CAC) of
      the protein forming the complex and the critical micelle concentration (CMC *) of
      SDS in the presence of protein, at different alcohol concentrations, were
      determined. It was found in both cases that the addition of alcohol does not
      produce a significant change in the CAC, whereas the CMC * displays variation
      with alcohol concentration that shows an inversion in the ranges 0.05-0.06
      ethanol mole fraction and 0.02-0.03 propan-2-ol mole fraction. This suggests
      that, in contrast with the CAC behaviour, the major factor that drives SDS
      micellization in the presence of protein is the variation in water structure.
      Results also suggest that it occurs in the same way for both proteins, where
      electrostatic interactions are the main force in the formation of the complex.
      Conversely, hydrophobic interactions play the dominant role at the micellization
      stage, and only the extent of the interaction between protein:surfactant
      aggregates and surfactant species seems to depend on protein nature.

PMID- 16441178
TI  - Mineralised tissues as nanomaterials: analysis by atomic force microscopy.
AB  - Mineralised tissues, such as bone, consist of two material phases: collagen
      protein fibrils that form the structural models upon which the mineral, calcium
      hydroxyapatite, is subsequently deposited. Collagen and mineral are removed in a
      three-dimensional manner by osteoclasts during bone turnover in skeletal growth
      or repair, and matrix proteins are replaced by the synthetic activity of
      osteoblasts and then calcify. The resolution of atomic force microscopy and use
      of unmodified, fully calcified samples has enabled the imaging of the overall
      bone and dentine structure, including collagen and mineral phases. Mineral
      crystals, in the diameter size range of 225 nm up to 1.4 microm, were found in
      unmodified bone and dentine respectively. D-banded collagen is observed in
      dentine after acid treatment and in bone after osteoclast-mediated matrix
      resorption; axial periodicity values of approximately 67 and 69 nm are observed,
      respectively. These experimental approaches have enabled the structure of
      mineralised tissues to be examined in native samples and will facilitate the
      study of bone structure in important clinical disorders of the skeleton, such as
      osteoporosis.

PMID- 16441179
TI  - Electrokinetic measurements of membrane capacitance and conductance for
      pancreatic beta-cells.
AB  - Membrane capacitance and membrane conductance values are reported for insulin
      secreting cells (primary -cells and INS-1 insulinoma cells), determined using the
      methods of dielectrophoresis and electrorotation. The membrane capacitance value
      of 12.57 (+/-1.46) mFm(-2), obtained for -cells, and the values from 9.96 (+/
      1.89) mFm(-2) to 10.65 (+/-2.1) mFm(-2), obtained for INS-1 cells, fall within
      the range expected for mammalian cells. The electrorotation results for the INS-1
      cells lead to a value of 36 (+/-22) Sm(-2) for the membrane conductance
      associated with ion channels, if values in the range 2-3 nS are assumed for the
      membrane surface conductance. This membrane conductance value falls within the
      range reported for INS cells obtained using the whole-cell patch-clamp technique.
      However, the total 'effective' membrane conductance value of 601 (+/-182) Sm(-2)
      obtained for the INS-1 cells by dielectrophoresis is significantly larger (by a
      factor of around three) than the values obtained by electrorotation. This could
      result from an increased membrane surface conductance, or increased passive
      conduction of ions through membrane pores, induced by the larger electric field
      stresses experienced by cells in the dielectrophoresis experiments.

PMID- 16441180
TI  - Surface-enhanced Raman spectroscopy biosensors: excitation spectroscopy for
      optimisation of substrates fabricated by nanosphere lithography.
AB  - In the 28 years since its discovery, surface-enhanced Raman scattering (SERS) has
      progressed from model system studies of pyridine on a roughened silver electrode
      to state-of-the-art surface science studies and real-world sensing applications.
      Each year, the number of SERS publications increases as nanoscale material design
      techniques advance and the importance of trace analyte detection increases. To
      achieve the lowest limits of detection, both the relationship between surface
      nanostructure and laser excitation wavelength and the analyte-surface binding
      chemistry must be carefully optimised. This work exploits the highly tunable
      nature of nanoparticle optical properties to establish the optimisation
      conditions. Two methods are used to study the optimised conditions of the SERS
      substrate: plasmon-sampled and wavelength-scanned surfaced Raman excitation
      spectroscopy (SERES). The SERS enhancement condition is optimised when the energy
      of the localised surface plasmon resonance of the nanostructures lies between the
      energy of the excitation wavelength and the energy of the vibration band of
      interest. These optimised conditions enabled the development of SERS-based
      sensors for the detection of a Bacillus anthracis biomarker and glucose in a
      serum-protein matrix.

PMID- 16441181
TI  - Tissue engineering and regenerative medicine: manufacturing challenges.
AB  - Tissue engineering and regenerative medicine are interdisciplinary fields that
      apply principles of engineering and life sciences to develop biological
      substitutes, typically composed of biological and synthetic components, that
      restore, maintain or improve tissue function. Many tissue engineering
      technologies are still at a laboratory or pre-commercial scale. The short review
      paper describes the most significant manufacturing and bio-process challenges
      inherent in the commercialisation and exploitation of the exciting results
      emerging from the biological and clinical laboratories exploring tissue
      engineering and regenerative medicine. A three-generation road map of the
      industry has been used to structure a view of these challenges and to define
      where the manufacturing community can contribute to the commercial success of the
      products from these emerging fields. The first-generation industry is
      characterised by its demonstrated clinical applications and products in the
      marketplace, the second is characterised by emerging clinical applications, and
      the third generation is characterised by aspirational clinical applications. The
      paper focuses on the cost reduction requirement of the first generation of the
      industry to allow more market penetration and consequent patient impact. It
      indicates the technological requirements, for instance the creation of three
      dimensional tissue structures, and value chain issues in the second generation of
      the industry. The third-generation industry challenges lie in fundamental
      biological and clinical science. The paper sets out a road map of these
      generations to identify areas for research.

PMID- 16441182
TI  - Angiopoietin-2: modulator of vascular permeability in acute lung injury?

PMID- 16441183
TI  - Spatial scaling factors explain eccentricity effects on face ERPs.
AB  - Event-related potential (ERP) studies consistently have described a strong, face
      sensitive response termed the N170. This component is maximal at the fovea and
      decreases strongly with eccentricity, a result that could suggest a foveal bias
      in the cortical generators responsible for face processing. Here we demonstrate
      that scaling stimulus size according to V1 cortical magnification factor can
      virtually eliminate face-related eccentricity effects, indicating that
      eccentricity effects on face ERPs are largely due to low-level visual factors
      rather than high-level cortical specialization for foveal stimuli.

PMID- 16441184
TI  - Visual illusions based on single-field contrast asynchronies.
AB  - A single-field contrast asynchrony refers to a stimulus configuration in which
      there is a single temporally modulated field and multiple sources of contrast
      information; the sources of contrast information modulate at different temporal
      phases or at different temporal frequencies. In this paper we show how single
      field contrast asynchronies can lead to a wide variety of visual illusions. We
      investigate, in depth, the window shade/rocking disk configuration, in which a
      temporally modulated disk is surrounded by a split annulus (i.e., the top half is
      dark, and the bottom half is light). When the annulus is thick, the disk appears
      spatially inhomogeneous (shading); when the annulus is thin, the disk appears to
      rock back and forth (shifting). We measure the proportion of trials that a disk
      appears to shade or, on separate trials, appears to shift as a function of
      modulation amplitude, surround thickness, temporal frequency, and disk size. We
      account for the shading effects by postulating a combination of separate first-
      and second-order responses and/or a multi-scale spatial filtering process. We
      account for the shifting effects by examining four elemental motion conditions.
      For luminance modulation, the direction of the shift follows the same pattern as
      that produced by the rectified output of an array of spatial center-surround
      filters applied to the X, t plot. For equiluminant modulation, the direction of
      the shifts is consistent with a sequence-tracking (or third-order) motion
      response.

PMID- 16441186
TI  - Range- and domain-specific exaggeration of facial speech.
AB  - Is it possible to exaggerate the different ways in which people talk, just as we
      can caricature their faces? In this paper, we exaggerate animated facial movement
      to investigate how the emotional manner of speech is conveyed. Range-specific
      exaggerations selectively emphasized emotional manner whereas domain-specific
      exaggerations of differences in duration did not. Range-specific exaggeration
      relative to a time-locked average was more effective than absolute exaggeration
      of differences from the static, neutral face, despite smaller absolute
      differences in movement. Thus, exaggeration is most effective when the average
      used captures shared properties, allowing task-relevant differences to be
      selectively amplified. Playing the stimuli backwards showed that the effects of
      exaggeration were temporally reversible, although emotion-consistent ratings for
      stimuli played forwards were higher overall. Comparison with silent video showed
      that these stimuli also conveyed the intended emotional manner, that the relative
      rating of animations depends on the emotion, and that exaggerated animations were
      always rated at least as highly as video. Explanations in terms of key frame
      encoding and muscle-based models of facial movement are considered, as are
      possible methods for capturing timing-based cues.

PMID- 16441185
TI  - Stereo sensitivity depends on stereo matching.
AB  - Stereoacuity thresholds, measured with bar targets, rise as the absolute
      disparity of the bars is increased. One explanation for this rise is that, as the
      bars are moved away from the fixation plane, the stereo system uses coarser
      mechanisms to encode the bars' disparity; coarse mechanisms are insensitive to
      small changes in target disparity, resulting in higher thresholds. To test this
      explanation, we measured stereoacuity with a 6 degrees wide 3 cpd grating
      presented in a rectangular envelope. We varied the disparity of the grating and
      its edges (envelope) parametrically from 0 to 20 arcmin (i.e., through one full
      period). To force observers to make judgments based on carrier disparity, we then
      varied the interocular phase incrementally from trial-to-trial while keeping edge
      disparity fixed for a given block of trials. The pedestal phase disparity of the
      grating necessarily cycles through 360 degrees, back to zero disparity, as the
      edge disparity increases monotonically from 0 to 20 arcmin. Unlike mechanisms
      that respond to bars, the mechanism that responds to the interocular phase
      disparity of the grating should have the same sensitivity at 20 arcmin disparity
      (360 degrees of phase) as it has at zero disparity. So, if stereoacuity were
      determined by the most sensitive mechanism, thresholds should oscillate with the
      pedestal phase disparity. However, these gratings are perceived in depth at the
      disparity of their edges. If stereoacuity were instead determined by the stereo
      matching operations that generate perceived depth, thresholds should rise
      monotonically with increasing edge disparity. We found that the rise in grating
      thresholds with increasing edge disparity was monotonic and virtually identical
      to the rise in thresholds observed for bars. Stereoacuity is contingent on stereo
      matching.

PMID- 16441187
TI  - Adaptation to the induced effect stimulus normalizes surface slant perception and
      recalibrates eye position signals for azimuth.
AB  - A frontoparallel plane viewed with unequal vertical magnification of the two
      ocular images appears rotated about a vertical axis (i.e., induced effect; Ogle,
      1938). Several experiments were conducted to investigate changes in the visual
      system that occurred after adapting to the induced effect. Adaptation at 57 cm
      was tested using tall stimuli at various viewing distances to test for the
      adaptation of vertical size ratio (VSR) information and normalization of the
      slant percept. When aftereffects were expressed in units of slant, they were
      larger at 57 cm than other test distances and were not significantly different
      from each other at other distances. Short stimuli were used to test adaptation of
      eye position signals for azimuth. The aftereffects were in the opposite direction
      to those measured with tall stimuli. The combined results suggest that the visual
      system normalizes slant percepts based on the surface slant of the adaptation
      stimulus and when there is a conflict between VSR signals and eye position cues
      for azimuth that the primary eye position signal for azimuth is recalibrated
      toward the direction indicated by the binocular differential vertical
      magnification in the adaptation stimulus.

PMID- 16441188
TI  - Human S-cone vision: relationship between perceptive field and ganglion cell
      dendritic field.
AB  - We measured the S-cone contrast threshold for stimuli of different size modulated
      along the white -90 deg direction in the isoluminant plane of DKL color space.
      The stimuli were presented at eccentricities of 5-30 deg in the horizontal
      temporal retinal meridian. Ricco's area of complete spatial summation was
      estimated using a bilinear fit of the log threshold/log area function. Ricco's
      area increased towards the retinal periphery to include an increasing number of S
      cones while remaining 1.6-1.8 times larger than the dendritic field area of the
      small bistratified and parasol retinal ganglion cells. Assuming constant coverage
      factor by the dendritic field, Ricco's area incorporated a constant number (three
      to four) of small bistratified cells. It was also found that the threshold
      contrast for stimuli that matched Ricco's area was constant across the studied
      eccentricity range, similar to previous findings for achromatic vision. Our data
      support the point of view that this invariance is the result of a constant number
      of cells involved in stimulus detection.

PMID- 16441190
TI  - Illumination estimation in three-dimensional scenes with and without specular
      cues.
AB  - We report the results of three experiments in which observers judged the albedo
      of surfaces at different locations in rendered, three-dimensional scenes
      consisting of two rooms connected by a doorway. All surfaces composing the rooms
      were achromatic and Lambertian, and a gradient of illumination increased with
      depth. Observers made asymmetric albedo matches between a standard surface placed
      in the rooms at different depths along the line of sight and an adjustable
      surface at a fixed location. In Experiment 1, gradients of intensity on the
      walls, floor, and ceiling of the scene, as well as its three-dimensional
      structure, provided information about variations in the intensity of illumination
      across depth (the illumination profile). In Experiment 2, specular spheres
      provided an additional veridical cue to the illumination profile. We sought to
      determine whether observers would make use of this additional cue. They did: all
      observers exhibited a greater degree of lightness constancy in Experiment 2 than
      in Experiment 1. In Experiment 3, the specular spheres reflected an illumination
      profile in conflict with that signaled by the other cues in the scene. We found
      that observers chose albedo matches consistent with an illumination profile that
      was a mixture of the illumination profiles signaled by the specular spheres and
      by the remaining cues.

PMID- 16441191
TI  - An oblique effect for local motion: psychophysics and natural movie statistics.
AB  - Human perception of visual motion is thought to involve two stages--estimation of
      local motion (i.e., of small features) and global motion (i.e., of larger
      objects)--identified with cortical areas V1 and MT, respectively. We asked if
      poor discrimination of oblique compared to cardinal directions (the oblique
      effect for motion; OEM) reflects a deficit in local or in global motion
      processing. We used an equivalent noise (EN) paradigm--where one measures
      direction discrimination thresholds in the presence of directional variability-
      to quantify local and global limits. We report that the OEM diminishes with
      increasing directional variability, indicating that global motion processing (the
      number of local motion signals pooled) is equal across all directions and that
      the OEM is attributable to anisotropies in local motion processing. To
      investigate the origin of this effect, we measured local motion statistics from
      natural movies (filmed from the point of view of a walking observer). This
      analysis reveals that the distribution of local directional energy on the oblique
      directions tends to be broader, and frequently more asymmetric, than on the
      cardinal directions. If motion detectors are optimized to deal with our visual
      world then such anisotropies likely explain the local nature of the OEM.

PMID- 16441189
TI  - Focus cues affect perceived depth.
AB  - Depth information from focus cues--accommodation and the gradient of retinal blur
      -is typically incorrect in three-dimensional (3-D) displays because the light
      comes from a planar display surface. If the visual system incorporates
      information from focus cues into its calculation of 3-D scene parameters, this
      could cause distortions in perceived depth even when the 2-D retinal images are
      geometrically correct. In Experiment 1 we measured the direct contribution of
      focus cues to perceived slant by varying independently the physical slant of the
      display surface and the slant of a simulated surface specified by binocular
      disparity (binocular viewing) or perspective/texture (monocular viewing). In the
      binocular condition, slant estimates were unaffected by display slant. In the
      monocular condition, display slant had a systematic effect on slant estimates.
      Estimates were consistent with a weighted average of slant from focus cues and
      slant from disparity/texture, where the cue weights are determined by the
      reliability of each cue. In Experiment 2, we examined whether focus cues also
      have an indirect effect on perceived slant via the distance estimate used in
      disparity scaling. We varied independently the simulated distance and the focal
      distance to a disparity-defined 3-D stimulus. Perceived slant was systematically
      affected by changes in focal distance. Accordingly, depth constancy (with respect
      to simulated distance) was significantly reduced when focal distance was held
      constant compared to when it varied appropriately with the simulated distance to
      the stimulus. The results of both experiments show that focus cues can contribute
      to estimates of 3-D scene parameters. Inappropriate focus cues in typical 3-D
      displays may therefore contribute to distortions in perceived space.

PMID- 16441192
TI  - Symmetry impedes symmetry discrimination.
AB  - Objects in the world, natural and artificial alike, are often bilaterally
      symmetric. The visual system is likely to take advantage of this regularity to
      encode shapes for efficient object recognition. The nature of encoding a
      symmetric shape, and of encoding any departure from it, is therefore an important
      matter in visual perception. We addressed this issue of shape encoding
      empirically, noting that a particular encoding scheme necessarily leads to a
      specific profile of sensitivity in perceptual discriminations. We studied
      symmetry discrimination using human faces and random dots. Each face stimulus was
      a frontal view of a three-dimensional (3-D) face model. The 3-D face model was a
      linearly weighted average (a morph) between the model of an original face and
      that of the corresponding mirror face. Using this morphing technique to vary the
      degree of asymmetry, we found that, for faces and analogously generated random
      dot patterns alike, symmetry discrimination was worst when the stimuli were
      nearly symmetric, in apparent opposition to almost all studies in the literature.
      We analyzed the previous work and reconciled the old and new results using a
      generic model with a simple nonlinearity. By defining asymmetry as the minimal
      difference between the left and right halves of an object, we found that the
      visual system was disproportionately more sensitive to larger departures from
      symmetry than to smaller ones. We further demonstrated that our empirical and
      modeling results were consistent with Weber-Fechner's and Stevens's laws.

PMID- 16441193
TI  - All Pulfrich-like illusions can be explained without joint encoding of motion and
      disparity.
AB  - In the Pulfrich effect, an interocular time delay results in the perception of
      depth. Two modified versions, the stroboscopic Pulfrich effect and dynamic visual
      noise with a delay, are generally explained by postulating an early stage of
      space/time-inseparable filtering, encoding motion and disparity jointly. However,
      most disparity sensors in monkey V1 do not show joint motion/disparity encoding,
      and we recently showed that depth perception in the stroboscopic Pulfrich effect
      is equally compatible with space/time-separable filtering. Here, we demonstrate
      that this filtering can be implemented with a population of physiologically
      plausible energy model units. Similar results are obtained whether the neurons
      are pure disparity sensors (like most V1 neurons) or joint motion/disparity
      sensors (like MT). We also demonstrate that the dynamic noise stimulus produces
      correlations between the activity in pure disparity sensors, and in a separate
      population of pure motion sensors. These correlations are sufficient to explain
      the percept. Thus, joint encoding of motion and disparity is not required to
      explain depth perception in Pulfrich-like stimuli: a brain which encoded motion
      and disparity in entirely separate neuronal pathways could still experience all
      of these illusions.

PMID- 16441194
TI  - Size matters, but not for everyone: individual differences for contrast
      discrimination.
AB  - It is very well known that contrast detection thresholds improve with the size of
      a grating-type stimulus, but it is thought that the benefit of size is abolished
      for contrast discriminations well above threshold [e.g., Legge, G. E., & Foley,
      J. M. (1980)]. Here we challenge the generality of this view. We performed
      contrast detection and contrast discrimination for circular patches of sine wave
      grating as a function of stimulus size. We confirm that sensitivity improves with
      approximately the fourth-root of stimulus area at detection threshold (a log-log
      slope of -0.25) but find individual differences (IDs) for the suprathreshold
      discrimination task. For several observers, performance was largely unaffected by
      area, but for others performance first improved (by as much as a log-log slope of
      -0.5) and then reached a plateau. We replicated these different results several
      times on the same observers. All of these results were described in the context
      of a recent gain control model of area summation [Meese, T. S. (2004)], extended
      to accommodate the multiple stimulus sizes used here. In this model, (i)
      excitation increased with the fourth-root of stimulus area for all observers, and
      (ii) IDs in the discrimination data were described by IDs in the relation between
      suppression and area. This means that empirical summation in the contrast
      discrimination task can be attributed to growth in suppression with stimulus size
      that does not keep pace with the growth in excitation.

PMID- 16441196
TI  - Effects of partial occlusion on perceived slant difference.
AB  - When two slanted surfaces are placed in proximity, the perceived slant difference
      between them is exaggerated. This effect has been called slant contrast. When a
      partial occluder is presented in front of the gap between them, the perceived
      slant difference between the surfaces is reduced. We refer to this reduction in
      perceived slant difference as stereo-slant assimilation. We investigated two
      properties of the occluder that might affect perceived stereo-slant difference.
      Three vertically aligned random-dot patterns were presented either with a partial
      occluder over the gaps between them or without it. Observers judged the perceived
      slant difference between the center pattern and two surround random-dot patterns
      that had the same slant. The perceived slant difference was reduced when the
      partial occluder was present. We varied stereo-depth and slant of the occluder
      and found that the decreased perceived slant difference was not due to either of
      these. Note that the surfaces were all simulated and presented on a computer
      screen and the results may not apply to real surfaces. The effect of the occluder
      on perceived slant differences could have resulted from either a reduction of
      slant contrast or an increase of slant assimilation.

PMID- 16441195
TI  - A luminous efficiency function, V*(lambda), for daylight adaptation.
AB  - We propose a new luminosity function, V*(lambda), that improves upon the original
      CIE 1924 V(lambda) function and its modification by D. B. Judd (1951) and J. J.
      Vos (1978), while being consistent with a linear combination of the A. Stockman &
      L. T. Sharpe (2000) long-wavelength-sensitive (L) and middle-wavelength-sensitive
      (M) cone fundamentals. It is based on experimentally determined 25 Hz, 2 degrees
      diameter, heterochromatic (minimum) flicker photometric data obtained from 40
      observers (35 males, 5 females) of known genotype, 22 with the serine variant
      L(ser180), 16 with the alanine L(ala180) variant, and 2 with both variants of the
      L-cone photopigment. The matches, from 425 to 675 nm in 5-nm steps, were made on
      a 3 log troland xenon white (correlated color temperature of 5586 K but
      tritanopically metameric with CIE D65 standard daylight for the Stockman and
      Sharpe L- and M-cone fundamentals in quantal units) adapting field of 16 degrees
      angular subtense, relative to a 560-nm standard. Both the reference standard and
      test lights were kept near flicker threshold so that, in the region of the
      targets, the total retinal illuminance averaged 3.19 log trolands. The advantages
      of the new function are as follows: it forms a consistent set with the new
      proposed CIE cone fundamentals (which are the Stockman & Sharpe 2000 cone
      fundamentals); it is based solely on flicker photometry, which is the standard
      method for defining luminance; it corresponds to a central 2 degrees viewing
      field, for which the basic laws of brightness matching are valid for flicker
      photometry; its composition of the serine/alanine L-cone pigment polymorphism
      (58:42) closely matches the reported incidence in the normal population (56:44;
      Stockman & Sharpe, 1999); and it specifies luminance for a reproducible, standard
      daylight condition. V*(lambda) is defined as 1.55L(lambda) + M(lambda), where
      L(lambda) and M(lambda) are the Stockman & Sharpe L- & M-cone (quantal)
      fundamentals. It is extrapolated to wavelengths shorter than 425 nm and longer
      than 675 nm using the Stockman & Sharpe cone fundamentals.

PMID- 16441197
TI  - The highest luminance anchoring rule in achromatic color perception: some
      counterexamples and an alternative theory.
AB  - It has been hypothesized that lightness is computed in a series of stages
      involving: (1) extraction of local contrast or luminance ratios at borders; (2)
      edge integration, to combine contrast or luminance ratios across space; and (3)
      anchoring, to relate the relative lightness scale computed in Stage 2 to the
      scale of real-world reflectances. The results of several past experiments have
      been interpreted as supporting the highest luminance anchoring rule, which states
      that the highest luminance in a scene always appears white. We have previously
      proposed a quantitative model of achromatic color computation based on a distance
      dependent edge integration mechanism. In the case of two disks surrounded by
      lower luminance rings, these two theories--highest luminance anchoring and
      distance--dependent edge integration-make different predictions regarding the
      luminance of a matching disk required to for an achromatic color match to a test
      disk of fixed luminance. The highest luminance rule predicts that luminance of
      the ring surrounding the test should make no difference, whereas the edge
      integration model predicts that increasing the surround luminance should reduce
      the luminance required for a match. The two theories were tested against one
      another in two experiments. The results of both experiments support the edge
      integration model over the highest luminance rule.

PMID- 16441198
TI  - Endogenous attention prolongs dominance durations in binocular rivalry.
AB  - We investigated the effects of attention on dominance durations during binocular
      rivalry. In a series of three experiments, observers performed several tasks
      while viewing rival stimuli to ensure and control deployment of attention. We
      found that endogenous attention can prolong dominance durations of attended
      stimulus. We developed a novel single-task procedure where observer's responses
      in an attentional task were used to objectively estimate dominance durations of
      the attended stimulus. Using this procedure, we showed that paying attention to
      the stimulus features involved in rivalry is necessary for prolonging dominance
      durations--mere engagement of attention during rivalry was insufficient. Finally,
      we were able to simulate the effects of endogenous attention by doubling the
      contrast of the attended stimulus while it was dominant. Attention may increase
      the apparent contrast of the attended stimulus, thereby prolonging its dominance
      duration. Overall, our results indicate that dominance durations in rivalry can
      be prolonged when observers are performing an attentionally demanding task on the
      rival stimulus.

PMID- 16441199
TI  - The combination of vision and touch depends on spatial proximity.
AB  - The nervous system often combines visual and haptic information about object
      properties such that the combined estimate is more precise than with vision or
      haptics alone. We examined how the system determines when to combine the signals.
      Presumably, signals should not be combined when they come from different objects.
      The likelihood that signals come from different objects is highly correlated with
      the spatial separation between the signals, so we asked how the spatial
      separation between visual and haptic signals affects their combination. To do
      this, we first created conditions for each observer in which the effect of
      combination--the increase in discrimination precision with two modalities
      relative to performance with one modality--should be maximal. Then under these
      conditions, we presented visual and haptic stimuli separated by different spatial
      distances and compared human performance with predictions of a model that
      combined signals optimally. We found that discrimination precision was
      essentially optimal when the signals came from the same location, and that
      discrimination precision was poorer when the signals came from different
      locations. Thus, the mechanism of visual-haptic combination is specialized for
      signals that coincide in space.

PMID- 16441200
TI  - Unfocused spatial attention underlies the crowding effect in indirect form
      vision.
AB  - We studied mechanisms underlying the crowding effect in indirect form vision by
      measuring recognition contrast sensitivity of a character with flankers to the
      left and right. Attentional and featural contributions to the effect can be
      separated by a new paradigm that distinguishes pattern location errors from
      pattern recognition errors and further by manipulating the focusing of spatial
      attention through a positional cue, appearing 150 ms before the target.
      Measurements were on the horizontal meridian, at 1, 2, and 4 deg eccentricity,
      and a range of flankers' distances were used. Our results show that in normal
      indirect viewing, the impairment of character recognition by crowding is--in
      particular at intermediate flanker distances--caused to a large part by spatially
      imprecise focusing of attention. In contrast, the enhancement of performance by a
      transient positional cue seems mediated through a separate attentional mechanism
      such that attentional locus and focus are controlled independently. Our results
      furthermore lend psychophysical support to a separate coding of the what and
      where in pattern recognition.

PMID- 16441201
TI  - Synergistic center-surround receptive field model of monkey H1 horizontal cells.
AB  - Horizontal cells typical of the vertebrate retina are strongly coupled by gap
      junctions. The resulting horizontal cell network has extremely large receptive
      fields that extend well beyond the boundaries of a single dendritic tree. This
      network has been modeled as a syncytium of cytoplasm bounded by cell membrane
      (Lamb 1976; Naka & Rushton, 1967). Horizontal cells in the primate retina are
      also coupled by gap junctions, but their receptive fields are relatively small
      and in some cases may approximate the span of the dendritic tree of an individual
      cell (Packer & Dacey, 2002). The receptive field of the macaque H1 horizontal
      cell type has been modeled as the sum of two spatial components: a strong but
      small diameter excitatory center, and a weak but broad excitatory surround. Here
      we explore the hypothesis that the receptive field center of H1 cells derives
      from direct cone synaptic input and that the synergistic surround derives from
      gap-junctional coupling among H1 cell neighbors. We measured the receptive field
      structure of H1 cells in the presence of carbenoxolone, a gap junction blocker,
      to determine the effects of uncoupling center and surround components and
      compared these data to a neural simulation of the H1 network in which gap
      junctional conductance could be manipulated. Carbenoxolone reduced the surround
      component and eliminated irregularities in spatial structure thought to be
      associated with the surround. The effects of carbenoxolone could be mimicked by
      manipulating gap-junctional conductance in an H1 cell network simulation. These
      results provide strong support for the two-component model of H1 receptive field
      structure. In addition, carbenoxolone eliminated a slow depolarization following
      light onset thought to be mediated by cone-H1 feedback (Kamermans & Spekreijse,
      1999). Low concentrations of cobalt, a calcium channel blocker that spares gap
      junctions, had an effect similar to that of carbenoxolone but did not affect
      receptive field structure. These results are consistent with a calcium-mediated
      mechanism of feedback from H1 cells to cones that is independent of the
      synergistic two-component model of receptive field organization.

PMID- 16441202
TI  - Illusory motion from change over time in the response to contrast and luminance.
AB  - A striking illusion of motion is generated by static repeated asymmetric patterns
      (RAPs) such as Kitaoka's (2003) "Rotating Snakes" and Fraser and Wilcox's (1979)
      peripheral drift illusion. How do RAPs generate spurious motion signals, and what
      critical difference between RAPs and natural static scenes prevents the latter
      from appearing to move? Small involuntary eye movements during fixation have been
      suspected to play a critical role in these illusions, but here we give an account
      that does not depend on fixation jitter. We propose that these illusions result
      primarily from fast and slow changes over time in the neuronal representation of
      contrast ("contrast-driven RAPs") or luminance ("luminance-driven RAPs"). We show
      that temporal phase advance in the neural response at high contrast can account
      for the early, fast motion in contrast-driven RAPs (such as "Rotating Snakes")
      after each fixation change. An essential part of this explanation is that motion
      detectors fail to compensate for the dynamics of neuronal encoding. We argue that
      static natural patterns also generate local gain changes, but that these signals
      do not often trigger illusory motion because they are not usually aligned to
      drive global motion detectors. Movies in which real luminance changes over time,
      to mimic the proposed neuronal adaptations to contrast and luminance, evoke
      qualitatively similar percepts of motion. Experimental data are consistent with
      the explanation. Color and overall contrast both enhance the illusion.

PMID- 16441203
TI  - HIV epidemic in Cambodia, one of the poorest countries in Southeast Asia: a
      success story.

PMID- 16441206
TI  - Tigecycline: a novel glycylcycline antibiotic.
AB  - Tigecycline, the first-in-class glycylcycline, was developed to recapture the
      broad spectrum of activity of the tetracycline class and to treat patients with
      difficult-to-treat bacterial infections. Tigecycline's in vitro spectrum of
      activity encompasses aerobic, facultative and anaerobic Gram-positive and 
      negative bacteria, including antimicrobial-resistant bacteria such as methicillin
      resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and
      Enterococcus faecium, and extended-spectrum beta-lactamase-producing
      Enterobacteriaceae. Clinical trials involving patients with complicated skin and
      skin-structure infections and complicated intra-abdominal infections, including
      patients infected with methicillin-resistant S. aureus, demonstrated that
      tigecycline was bacteriologically and clinically effective with mild-to-moderate
      gastrointestinal adverse events (i.e., nausea, vomiting and diarrhea) the most
      commonly reported. Tigecycline is a promising new broad-spectrum parenteral
      monotherapy for the treatment of patients with Gram-positive and -negative
      bacterial infections.

PMID- 16441207
TI  - Prulifloxacin: a new antibacterial fluoroquinolone.
AB  - In the last few years, the antimicrobial activity, efficacy and relative safety
      of fluoroquinolones have made them attractive for the treatment of community
      acquired and nosocomial infections. Prulifloxacin is a new fluoroquinolone
      antibacterial agent with a broad spectrum of activity against Gram-positive and 
      negative bacteria. Prulifloxacin is available for oral use, and after absorption
      is metabolized in to the active form, ulifloxacin. It exhibits good penetration
      in target tissues and a long elimination half-life, allowing once-daily
      administration. A number of randomized, controlled clinical trials carried out in
      Europe demonstrated the efficacy of prulifloxacin in the treatment of urinary
      tract (acute uncomplicated and complicated) and respiratory tract infections
      (acute exacerbations of chronic bronchitis), in comparison with the most widely
      used drugs such as ciprofloxacin, co-amoxiclav and pefloxacin. Prulifloxacin was
      generally well tolerated. The most frequent adverse reactions observed in
      clinical trials were gastric pain, diarrhea, nausea and skin rash. This review
      focuses on the characteristics of prulifloxacin, summarizing the relevant
      preclinical and clinical data.

PMID- 16441208
TI  - Developments towards effective treatments for Nipah and Hendra virus infection.
AB  - Hendra and Nipah virus are closely related emerging viruses comprising the
      Henipavirus genus of the subfamily Paramyxovirinae and are distinguished by their
      ability to cause fatal disease in both animal and human hosts. In particular, the
      high mortality and person-to-person transmission associated with the most recent
      Nipah virus outbreaks, as well as the very recent re-emergence of Hendra virus,
      has confirmed the importance and necessity of developing effective therapeutic
      interventions. Much research conducted on the henipaviruses over the past several
      years has focused on virus entry, including the attachment of virus to the host
      cell, the identification of the virus receptor and the membrane fusion process
      between the viral and host cell membranes. These findings have led to the
      development of possible vaccine candidates, as well as potential antiviral
      therapeutics. The common link among all of the possible antiviral agents
      discussed here, which have also been developed and tested, is that they target
      very early stages of the infection process. The establishment and validation of
      suitable animal models of Henipavirus infection and pathogenesis are also
      discussed as they will be crucial in the assessment of the effectiveness of any
      treatments for Hendra and Nipah virus infection.

PMID- 16441209
TI  - Development of human monoclonal antibodies against diseases caused by emerging
      and biodefense-related viruses.
AB  - Polyclonal antibodies have a century-old history of being effective against some
      viruses; recently, monoclonal antibodies (mAbs) have also shown success. The
      humanized mAb Synagis (palivizumab), which is still the only mAb against a viral
      disease approved by the US FDA, has been widely used as a prophylactic measure
      against respiratory syncytial virus infections in neonates and immunocompromised
      individuals. The first fully human mAbs against two other paramyxoviruses, Hendra
      and Nipah virus, which can cause high (up to 75%) mortality, were recently
      developed; one of them, m101, showed exceptional potency against infectious
      virus. In an amazing pace of research, several potent human mAbs targeting the
      severe acute respiratory syndrome coronavirus S glycoprotein that can affect
      infections in animal models have been developed months after the virus was
      identified in 2003. A potent humanized mAb with therapeutic potential was
      recently developed against the West Nile virus. The progress in developing
      neutralizing human mAbs against Ebola, Crimean-Congo hemorrhagic fever, vaccinia
      and other emerging and biodefense-related viruses is slow. A major problem in the
      development of effective therapeutic agents against viruses, including
      therapeutic antibodies, is the viruses' heterogeneity and mutability. A related
      problem is the low binding affinity of crossreactive antibodies able to
      neutralize a variety of primary isolates. Combinations of mAbs or mAbs with other
      drugs, and/or the identification of potent new mAbs and their derivatives that
      target highly conserved viral structures, which are critical for virus entry into
      cells, are some of the possible solutions to these problems, and will continue to
      be a major focus of antiviral research.

PMID- 16441210
TI  - Development of treatment strategies to combat Ebola and Marburg viruses.
AB  - Ebola and Marburg viruses are emerging/re-emerging pathogens that pose a
      significant threat to human health. These naturally occurring viral infections
      frequently cause a lethal hemorrhagic fever in humans and nonhuman primates. The
      disastrous consequences of infection with these viruses have been pursued as
      potential biological weapons. To date, there are no therapeutic options available
      for the prophylaxis or treatment of infected individuals. The recognition that
      Ebola and Marburg viruses may be exploited as biological weapons has resulted in
      major efforts to develop modalities to counter infection. In this review, select
      technologies and approaches will be highlighted as part of the critical path for
      the development of therapeutics to ameliorate the invariably devastating outcomes
      of human filoviral infections.

PMID- 16441211
TI  - Epstein-Barr virus-associated lymphomas.
AB  - Following Epstein and colleagues' ground-breaking discovery of Epstein-Barr virus
      by electron microscopy of Burkitt's lymphoma cell lines, there came the
      observation that Epstein-Barr virus induces immortalization of B cells in vitro.
      Thus, initial hopes were of a virus confined to equatorial Africa with a causal
      link to a particular subtype of childhood lymphoma. Over the past 40 years there
      has been great progress towards understanding the biology and epidemiology of
      Epstein-Barr virus, which conclusively show that these early ideas were overly
      simplistic. It is now known that Epstein-Barr virus has a seroprevalence of
      approximately 95% worldwide, and persists for life within host B lymphocytes.
      Infection in New World primates leads to lymphoma and inoculation of peripheral
      blood mononuclear cells from Epstein-Barr virus-seropositive subjects into severe
      combined immunodeficiency mice results in B-cell lymphoproliferative disorders.
      Epstein-Barr virus is now known to be implicated in a range of lymphoid and other
      malignancies, and this association will be the subject of this review.

PMID- 16441212
TI  - Epidemiology and treatment of community-associated methicillin-resistant
      Staphylococcus aureus in children.
AB  - Similar to the epidemiology of methicillin-sensitive Staphylococcus aureus,
      community-associated methicillin-resistant S. aureus infections occur in children
      in different regions of the USA and throughout the world. Although minor skin and
      soft-tissue infections predominate, life-threatening invasive disease and death
      can result. The novel genetic elements, staphylococcal cassette chromosome mec IV
      and V, explain the narrow antibiotic resistance pattern, and suggest the
      mechanism of spread among staphylococci. Panton-Valentine leukocidin apparently
      plays a role in its pathogenesis. Clindamycin therapy is often effective for
      treatment, but inducible resistance can develop if the isolate exhibits macrolide
      resistance due to the erm mechanism. Other drugs displaying in vitro activity
      against community-associated methicillin-resistant S. aureus include trimethoprim
      sulfamethoxazole, tetracyclines, quinolones, linezolid and vancomycin. While
      experience in pediatric patients is limited, daptomycin, ketolides,
      glycylcyclines, newer glycopeptides and beta-lactamase-stable cephalosporins may
      be useful in the future. Further research could include well-designed studies of
      mechanisms of virulence, continued surveillance of changes in pathogenicity and
      susceptibility, as well as treatment effectiveness.

PMID- 16441213
TI  - Role of infection and antimicrobial therapy in acute exacerbations of chronic
      obstructive pulmonary disease.
AB  - Over the past several years, the significance of acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD) in patients with chronic airflow
      obstruction has become increasingly apparent due to the impact these episodes
      have on the natural history of disease. It is now known that frequent AECOPD can
      adversely affect a patient's health-related quality of life and short- and long
      term pulmonary function. The economic burden of these episodes is also
      substantial. AECOPDs represent a local and systemic inflammatory response to both
      infectious and noninfectious stimuli, but the majority of episodes are likely
      related to bacterial or viral pathogens. Patients with purulent sputum and
      multiple symptoms are the most likely to benefit from treatment with antibiotics.
      Antibiotic choice should be tailored to the individual patient, taking into
      account the severity of the episode and host factors which might increase the
      likelihood of treatment failure. Current evidence suggests that therapeutic goals
      not only include resolution of the acute episode, but also prolonging the time to
      the next event. In the future, preventing exacerbations will likely become
      increasingly accepted as an additional therapeutic goal in chronic obstructive
      pulmonary disease patients.

PMID- 16441214
TI  - Trichomoniasis and its treatment.
AB  - Trichomonas vaginalis has long been recognized as a cause of infectious vaginitis
      in women. More recently, studies have demonstrated a significant burden of
      disease in men with urethritis or men at high risk for sexually transmitted
      diseases. There is increasing interest in this pathogen as more data accumulates
      linking it to HIV transmission and perinatal morbidity. New diagnostic methods
      have emerged that may increase sensitivity of diagnosis or improve point-of-care
      access to testing. Nitroimidazoles remain the mainstay of therapy. Metronidazole
      and tinidazole are highly effective as single-dose therapy. Unfortunately,
      despite the link between T. vaginalis infection and perinatal morbidity,
      nitroimidazole therapy during pregnancy remains controversial. Although
      metronidazole resistance is currently uncommon, pharmacological features and
      nitroimidazole resistance patterns suggest that tinidazole may be more effective
      in treating patients with metronidazole treatment failure. Alternatives to
      nitroimidazole therapy are few, and most have limited efficacy and significant
      toxicity.

PMID- 16441215
TI  - Pharmacological advances in the treatment of invasive candidiasis.
AB  - Invasive candidiasis is a common nosocomial infection, especially among the
      critically ill and immunocompromised patient populations. The recent
      standardization and increasing availability of antifungal susceptibility testing
      has the potential to optimize the selection of antifungal therapy. Treatment has
      been revolutionized in recent years with the marketing of several antifungal
      agents with excellent activity against Candida spp. These agents include the
      triazoles, fluconazole and voriconazole, and the echinocandin antifungals. While
      more expensive by acquisition cost, these newer agents are less toxic than the
      previously used drugs, and the triazoles offer the additional benefit of oral
      administration. The availability of new agents, future adoption of diagnostic
      tests for candidiasis, and susceptibility testing will have a major impact in the
      management of invasive candidiasis.

PMID- 16441216
TI  - Revision on tungiasis: treatment options and prevention.
AB  - The parasitic skin disease tungiasis occurs in many resource-poor communities in
      Latin America, the Caribbean and sub-Saharan Africa. The sand flea, Tunga
      penetrans, most commonly penetrates into the skin of the feet. Many individuals
      harbor a large number of embedded parasites and show significant morbidity.
      Standard treatment consists of surgical extraction of the flea and application of
      a topical antibiotic. There are no drugs available with proven effectiveness.
      Clinical trials performed in the last few years did not show very promising
      results. Thus, surgical extraction still remains the treatment of choice in
      patients with a low parasite load, such as tourists returning from endemic areas.
      Probably the best approach to reduce tungiasis-associated morbidity in heavily
      affected individuals is the application of a repellent to prevent the penetration
      of sand fleas. In the future, we should see new exciting data on the biology,
      epidemiology, therapy and control of tungiasis.

PMID- 16441223
TI  - A new therapeutic target for atherosclerosis treatment: interview with Uday
      Saxena. Interviewed by Emma Quigley.
AB  - Uday Saxena was appointed Chief Scientific Officer at Dr Reddy's Laboratories in
      2000. In this role he provides the leadership and general strategy for the
      company's drug discovery research into metabolic disorders, cardiovascular
      disorders, inflammation, cancer and anti-infectives. He is also a member of the
      company's Senior Management Council. He gained his PhD at the Memorial University
      of Newfoundland, his thesis covering biochemical and functional characterisation
      of rat C-reactive protein with respect to lipid, lipoprotein metabolism,
      atherosclerosis and inflammation. On completing his postdoctoral fellowship at
      Colombia University, he went onto work on various drug discovery projects as
      Senior Scientist and Principal Research Scientist at Parke-Davis Warner-Lambert
      and as Director and Vice-President for preclinical research at AtheroGenics,
      Inc., before undertaking his current position. Uday Saxena has written over 50
      peer-reviewed articles and invited reviews. He is currently on the Editorial
      Board of two international drug discovery-related journals including Expert
      Opinion on Therapeutic Targets.

PMID- 16441224
TI  - Targeting vascular endothelial growth factor in angina therapy.
AB  - Despite tremendous success of growth factor therapy in animal models, clinical
      trials have demonstrated minimal success. Vascular endothelial growth factors are
      perhaps the most potent inducers of angiogenesis in these animal models. This
      review outlines the biology of vascular endothelial growth factors in the context
      of myocardial angiogenesis with an emphasis on its effects on the endothelium. It
      also provides an overview of delivery strategies and summarises the preclinical
      and clinical evidence relating to exogenous growth factor delivery for myocardial
      angiogenesis with an emphasis on the key future challenges.

PMID- 16441225
TI  - Targeting Brn-3b in breast cancer therapy.
AB  - The Brn-3b POU domain transcription factor is elevated in a significant
      proportion of breast cancers and in neuroblastoma tumours, where it is associated
      with increased proliferation, anchorage-independent growth, faster and larger
      tumour growth in xenograft models, resistance to growth inhibitory stimuli and
      increased migratory potential. These effects are associated with the ability of
      Brn-3b to regulate specific genes associated with these processes. Reducing Brn
      3b can reverse many of these effects, suggesting that it may be possible to alter
      the growth and behaviour of tumour cells by abrogating Brn-3b in these cancers.
      This review discusses the effect of altering Brn-3b in these cancer cells and
      possible approaches to targeting Brn-3b as a strategy for therapy in treatment of
      breast cancers.

PMID- 16441226
TI  - The role of cellular FLICE inhibitory protein (c-FLIP) in the pathogenesis and
      treatment of cancer.
AB  - Protection from death receptor (DR)-mediated apoptosis has been proposed as an
      important step in the development of malignancy, enabling tumour cells not only
      to survive and escape antitumour immune responses, but also to develop resistance
      to chemotherapy or other cancer treatments. An important regulator of DR-induced
      death is the cellular FADD-like IL-1beta-converting enzyme inhibitory protein (c
      FLIP) which, when overexpressed, can protect tumour cells from apoptosis. This
      review focuses on the role of c-FLIP as a tumour progression factor, with
      particular emphasis on recent work from the authors' laboratory concerning the
      contribution of c-FLIP to the pathogenesis of Hodgkin's lymphoma. The possibility
      of targeting c-FLIP as an approach to the treatment of cancer and, in particular,
      Hodgkin's lymphoma is discussed.

PMID- 16441227
TI  - Targeting chaperones in transformed systems--a focus on Hsp90 and cancer.
AB  - The molecular chaperone Hsp90 is a protein with important roles in maintaining
      the functional stability and viability of cells under a transforming pressure.
      Cancer cells harbour mutated oncogenic proteins or proteins with dysregulated
      function and the chaperone is required to maintain their folded and functionally
      active conformation. In addition, by chaperoning key proteins such as Raf-1, Akt,
      survivin and hTERT, Hsp90 regulates signalling pathways necessary for the growth,
      survival and limitless replicative potential of most tumours. Important elements
      of the apoptotic pathways are also regulated by Hsp90. Overall, these
      characteristics propose Hsp90 as an important target of whose inhibition may aim
      at a wide-range of oncogenic transformations. Several years into Hsp90 research
      have shed light into the feasibility, but also the limitations, of such an
      approach. In this review, the authors present the current understanding on the
      relevance and possibility of translating Hsp90 inhibitors into therapeutic agents
      in cancer therapy.

PMID- 16441229
TI  - The small-molecule immune response modifier imiquimod--its mode of action and
      clinical use in the treatment of skin cancer.
AB  - Due to its good clinical efficacy against malignant skin tumours, the topical
      immune response modifier, imiquimod, has attracted much interest among
      researchers and clinicians alike. Imiquimod exerts its antitumoural effect, at
      least in part, through agonistic stimulation of TLR-7 and TLR-8 on dendritic
      cells, followed by NF-kappaB-dependent secretion of a multitude of pro
      inflammatory cytokines. The net result of this pro-inflammatory activity is a
      profound tumour-directed cellular immune response. Recent research has revealed
      an additional mode of action inasmuch as imiquimod interferes with adenosine
      receptor signalling, even in TLR-7- and TLR-8-negative cells, thereby presumably
      augmenting inflammatory signalling cascades. Moreover, at higher concentrations
      imiquimod also exerts direct proapoptotic activity against tumour cells. This
      mode of action appears to be independent of membrane-bound death receptors but is
      mediated, at least in part, through Bcl-2-dependent release of mitochondrial
      cytochrome c and subsequent caspase activation. Overall, a combination of several
      complementary antitumoural modes of action appears to underlie the great utility
      of imiquimod for treating cutaneous tumours.

PMID- 16441228
TI  - Protein lysine acetylation in normal and leukaemic haematopoiesis: HDACs as
      possible therapeutic targets in adult AML.
AB  - Several new therapeutic strategies are now considered for acute myelogenous
      leukaemia (AML), including modulation of protein lysine acetylation through
      inhibition of histone deacetylases (HDACs): a large group of enzymes that alters
      the acetylation and, thereby, the function of a wide range of nuclear and
      cytoplasmic proteins. Firstly, HDACs can deacetylate histones as well as
      transcription factors, and can modulate gene expression through both these
      mechanisms. Secondly, acetylation is an important post-translational modulation
      of several proteins involved in the regulation of cell proliferation,
      differentiation and apoptosis (e.g., p53, tubulin, heat-shock protein 90). The
      only HDAC inhibitors that have been investigated in clinical studies of AML are
      butyrate derivatives, valproic acid and depsipeptide. In the first studies, the
      drugs have usually been used as continuous therapy for several weeks or months,
      and in most studies the drugs were used alone or in combination with all-trans
      retinoic acid for treatment of patients with relapsed or primary resistant AML.
      Neurological toxicity and gastrointestinal side effects seem to be common for all
      three drugs. Complete haematological remission lasting for several months has
      been reported for a few patients (< 5% of included patients), whereas increased
      peripheral blood platelet counts seem more common and have been described both
      for patients with AML and myelodysplastic syndromes. Taken together, these
      studies suggest that HDAC inhibition can mediate antileukaemic effects in AML,
      but for most patients the clinical benefit seems limited and further studies of
      combination therapy are required.

PMID- 16441230
TI  - Targeting Aurora kinases in ovarian cancer.
AB  - Although recurrent epithelial ovarian cancer initially responds well to current
      first-line adjuvant therapy, eventually the disease becomes resistant to
      chemotherapy. Novel strategies are needed to reverse chemoresistance in order to
      treat relapsed ovarian cancer effectively. One strategy is to target aberrant
      expression activation of Aurora kinases that are essential for the regulation of
      chromosome segregation and cytokinesis during mitosis and which play a role in
      tumourigenesis and progression in a wide range of human tumours, including
      ovarian cancer. The purpose of this article is to review Aurora kinases and their
      inhibitors in human epithelial ovarian cancer as an impetus to the development of
      effective and less toxic regimens for ovarian cancer. In addition, this review
      tries to define the differences between cytotoxic chemotherapeutic agents and
      molecular therapeutic agents: both groups of agents have either a single specific
      target or multiple specific targets, while their differences lie in their
      toxicity profiles and the way to determine their dosages for further studies. The
      authors propose that Aurora kinase inhibitors be developed as molecular
      therapeutic agents in order to minimise their toxicities and maximise their
      antitumour activities for ovarian cancer treatment.

PMID- 16441231
TI  - From traditional Ayurvedic medicine to modern medicine: identification of
      therapeutic targets for suppression of inflammation and cancer.
AB  - Cancer is a hyperproliferative disorder that involves transformation,
      dysregulation of apoptosis, proliferation, invasion, angiogenesis and metastasis.
      Extensive research during the last 30 years has revealed much about the biology
      of cancer. Drugs used to treat most cancers are those that can block cell
      signalling, including growth factor signalling (e.g., epidermal growth factor);
      prostaglandin production (e.g., COX-2); inflammation (e.g., inflammatory
      cytokines: NF-kappaB, TNF, IL-1, IL-6, chemokines); drug resistance gene products
      (e.g., multi-drug resistance); cell cycle proteins (e.g., cyclin D1 and cyclin
      E); angiogenesis (e.g., vascular endothelial growth factor); invasion (e.g.,
      matrix metalloproteinases); antiapoptosis (e.g., bcl-2, bcl-X(L), XIAP, survivin,
      FLIP); and cellular proliferation (e.g., c-myc, AP-1, growth factors). Numerous
      reports have suggested that Ayurvedic plants and their components mediate their
      effects by modulating several of these recently identified therapeutic targets.
      However, Ayurvedic medicine requires rediscovery in light of our current
      knowledge of allopathic (modern) medicine. The focus of this review is to
      elucidate the Ayurvedic concept of cancer, including its classification, causes,
      pathogenesis and prevention; surgical removal of tumours; herbal remedies;
      dietary modifications; and spiritual treatments.

PMID- 16441232
TI  - Adipose targets for obesity drug development.
AB  - The prevalence of obesity is increasing rapidly in most parts of the world and
      effective therapeutic drugs are urgently needed. The discovery of leptin in 1994
      initiated a new understanding of adipose tissue function, and adipose tissue is
      now known to not only store and release fatty acids, but also to produce a wealth
      of factors that have an impact on the regulation of body weight and blood glucose
      homeostasis. Also, adipocytes express proteins that engage signalling pathways
      playing important roles in fuel substrate and energy metabolism. These proteins
      constitute a diverse array of adipose target candidates for the development of
      drugs to treat obesity. Some of these potential targets have been validated and
      are now in drug development stages, providing hope that the current obesity
      epidemic can be addressed by effective drug treatments in the near future.

PMID- 16441233
TI  - Shp2 as a therapeutic target for leptin resistance and obesity.
AB  - Most obese subjects exhibit leptin resistance, thus restricting the value of
      direct leptin administration for treatment of obesity. Understanding the leptin
      signalling mechanism has become crucial for design of novel therapeutic
      strategies for leptin-resistant/obese patients. The SH2-containing cytoplasmic
      tyrosine phosphatase Shp2 has recently been shown to play a critical role in
      leptin signalling and functions in hypothalamic control of energy balance and
      metabolism. Shp2 appears to downregulate the LepRb-STAT3 pathway while promoting
      extracellular-regulated kinase activation by leptin. Overall, Shp2 is a leptin
      signal enhancer, as evidenced by the obese and hyperleptinemic phenotype of
      mutant mice with Shp2 deleted in postmitotic forebrain neurons. Pharmaceutical
      enhancement of Shp2 activity may be a new approach worthy of consideration in
      clinical treatment of leptin resistance and obesity. This article discusses the
      significance of recent experimental data on Shp2 and also the prospects for using
      Shp2 as a therapeutic target for obese patients.

PMID- 16441234
TI  - Targeting matrix metalloproteases to improve cutaneous wound healing.
AB  - Wound repair is a physiological event in which tissue injury initiates a repair
      process leading to restoration of structure and function of the tissue. Cutaneous
      wound repair can be divided into a series of overlapping phases including
      formation of fibrin clot, inflammatory response, granulation tissue formation
      incorporating re-epithelialisation and angiogenesis and finally, matrix formation
      and remodelling. Matrix metalloproteases (MMPs) are a family of neutral proteases
      that play a vital role throughout the entire wound healing process. They regulate
      inflammation, degrade the extracellular matrix (ECM) to facilitate the migration
      of cells and remodel the new ECM. However, excessive MMP activity contributes to
      the development of chronic wounds. Selective control of MMP activity may prove to
      be a valuable therapeutic approach to promote healing of chronic ulcers. Recent
      evidence indicates that the anticoagulant, activated protein C may be useful in
      the treatment of non-healing wounds by preventing excessive protease activity
      through inhibition of inflammation and selectively increasing MMP-2 activity to
      enhance angiogenesis and re-epithelialisation.

PMID- 16441235
TI  - Targeting the PTPome in human disease.
AB  - Protein tyrosine phosphatases (PTPs) play vital roles in numerous cellular
      processes and are implicated in a growing number of human diseases, ranging from
      cancer to cardiovascular, immunological, infectious, neurological and metabolic
      diseases. There are at least 107 genes in the human genome, collectively referred
      to as the human 'PTPome'. Here the authors review the involvement of PTPs in
      human disease, discuss their potential as drug targets, and current efforts to
      develop PTP inhibitors for the treatment of human disease. Finally, the authors
      present their view of the future for PTPs as drug targets.

PMID- 16441236
TI  - Transcreener: screening enzymes involved in covalent regulation.
AB  - Enzymes that catalyse group transfer reactions comprise a significant fraction of
      the human proteome and are a rich source of drug targets because of their role in
      covalent regulatory cycles. Phosphorylation, glycosylation, sulfonation,
      methylation and acetylation represent some of the key types of group transfer
      reactions that modulate the function of diverse biomolecules through covalent
      modification. Development of high-throughput screening methods for these enzymes
      has been problematic because of the diversity of acceptor substrates. Recently,
      the authors developed a novel assay platform called Transcreener that relies upon
      fluorescence detection of the invariant reaction product of a group transfer
      reaction, usually a nucleotide. This platform enables screening of any isoform in
      a family of group transfer enzymes, with any acceptor substrate, using the same
      assay reagents.

PMID- 16441237
TI  - Ceramide as a target in emphysema.

PMID- 16441238
TI  - Collagen binding by the mannose receptor mediated through the fibronectin type II
      domain.
AB  - The macrophage mannose receptor is the prototype for a family of receptors each
      having an extracellular region consisting of an N-terminal cysteine-rich domain
      related to the R-type carbohydrate-recognition domain of ricin, a fibronectin
      type II domain and eight to ten domains related to C-type carbohydrate
      recognition domains. The mannose receptor acts as a molecular scavenger, clearing
      harmful glycoconjugates or micro-organisms through recognition of their defining
      carbohydrate structures. Cell-adhesion assays, as well as collagen-binding
      assays, have now been used to show that the mannose receptor can also bind
      collagen and that the fibronectin type II domain mediates this activity. Neither
      of the two types of sugar-binding domain in the receptor is involved in collagen
      binding. Fibroblasts expressing the mannose receptor adhere to type I, type III
      and type IV collagens, but not to type V collagen, and the adherence is inhibited
      by isolated mannose receptor fibronectin type II domain. The fibronectin type II
      domain shows the same specificity for collagen as the whole receptor, binding to
      type I, type III and type IV collagens. This is the first activity assigned to
      the fibronectin type II domain of the mannose receptor. The results suggest
      additional roles for this multifunctional receptor in mediating collagen
      clearance or cell-matrix adhesion.

PMID- 16441239
TI  - Removal of the glycosylphosphatidylinositol anchor from PrP(Sc) by cathepsin D
      does not reduce prion infectivity.
AB  - According to the protein-only hypothesis of prion propagation, prions are
      composed principally of PrP(Sc), an abnormal conformational isoform of the prion
      protein, which, like its normal cellular precursor (PrP(C)), has a GPI
      (glycosylphosphatidylinositol) anchor at the C-terminus. To date, elucidating the
      role of this anchor on the infectivity of prion preparations has not been
      possible because of the resistance of PrP(Sc) to the activity of PI-PLC
      (phosphoinositide-specific phospholipase C), an enzyme which removes the GPI
      moiety from PrP(C). Removal of the GPI anchor from PrP(Sc) requires denaturation
      before treatment with PI-PLC, a process that also abolishes infectivity. To
      circumvent this problem, we have removed the GPI anchor from PrP(Sc) in RML
      (Rocky Mountain Laboratory)-prion-infected murine brain homogenate using the
      aspartic endoprotease cathepsin D. This enzyme eliminates a short sequence at the
      C-terminal end of PrP to which the GPI anchor is attached. We found that this
      modification has no effect (i) on an in vitro amplification model of PrP(Sc),
      (ii) on the prion titre as determined by a highly sensitive N2a-cell based
      bioassay, or (iii) in a mouse bioassay. These results show that the GPI anchor
      has little or no role in either the propagation of PrP(Sc) or on prion
      infectivity.

PMID- 16441240
TI  - Dual-function protein in plant defence: seed lectin from Dolichos biflorus (horse
      gram) exhibits lipoxygenase activity.
AB  - Plant-pathogen interactions play a vital role in developing resistance to pests.
      Dolichos biflorus (horse gram), a leguminous pulse crop of the subtropics,
      exhibits amazing defence against attack by pests/pathogens. Investigations to
      locate the possible source of the indomitable pest resistance of D. biflorus,
      which is the richest source of LOX (lipoxygenase) activity, have led to a
      molecule that exhibits LOX-like functions. The LOX-like activity associated with
      the molecule, identified by its structure and stability to be a tetrameric
      lectin, was found to be unusual. The evidence for the lectin protein with LOX
      activity has come from (i) MALDI-TOF (matrix-assisted laser-desorption ionization
      time-of-flight) MS, (ii) N-terminal sequencing, (iii) partial sequencing of the
      tryptic fragments of the protein, (iv) amino acid composition, and (v) the
      presence of an Mn2+ ion. A hydrophobic binding site of the tetrameric lectin,
      along with the presence of an Mn2+ ion, accounts for the observed LOX like
      activity. This is the first ever report of a protein exhibiting both
      haemagglutination and LOX-like activity. The two activities are associated with
      separate loci on the same protein. LOX activity associated with this molecule
      adds a new dimension to our understanding of lectin functions. This observation
      has wide implications for the understanding of plant defence mechanisms against
      pests and the cellular complexity in plant-pathogen interactions that may lead to
      the design of transgenics with potential to impart pest resistance to other
      crops.

PMID- 16441241
TI  - Intracellular degradation of insulin and crinophagy are maintained by nitric
      oxide and cyclo-oxygenase 2 activity in isolated pancreatic islets.
AB  - BACKGROUND INFORMATION: Pancreatic beta-cells require an optimal insulin content
      to allow instantaneous secretion of insulin. This is maintained by insulin
      biosynthesis and intracellular degradation of insulin. Degradation may be
      effected by crinophagy, i.e. the fusion of secretory granules with lysosomes. IL
      1beta (interleukin 1beta) induces distinct changes of beta-cell lysosomes. To
      study the mechanisms for intracellular insulin degradation and crinophagy,
      isolated mouse pancreatic islets were exposed to IL-1beta and known pathways for
      IL-1beta actions were blocked. Intracellular insulin degradation was determined
      by following the fate of radioactively labelled insulin. Crinophagy was studied
      by ultrastructural analysis. The effects of blocking pathways for IL-1beta were
      monitored by measurements of nitrite and PGE(2) (prostaglandin E(2)). RESULTS: IL
      1beta caused an enhancement of islet intracellular insulin degradation and an
      increase in the lysosomal incorporation of beta-cell secretory granules. The
      effects of IL-1beta were abolished by aminoguanidine, a selective inhibitor of
      inducible NOS (nitric oxide synthase), or by rofecoxib, a specific inhibitor of
      COX-2 (cyclo-oxygenase 2). In the absence of IL-1beta, nitroarginine, which is a
      selective inhibitor of constitutive NOS, caused a decrease in intracellular
      degradation of insulin in parallel with a decreased production of NO and PGE(2)
      by the islets. CONCLUSIONS: The correlation between the enhanced intracellular
      insulin degradation and lysosomal changes caused by IL-1beta suggests that
      insulin degradation may be effected by crinophagy. Under physiological
      conditions, significant beta-cell degradation of insulin may depend on the
      activity of COX-2, possibly stimulated by endogenous NO.

PMID- 16441243
TI  - Epileptogenesis and rational therapeutic strategies.
AB  - The understanding of neurobiological mechanisms of epileptogenesis is essential
      for rational approaches for a possible disease modification as well as treatment
      of underlying causes of the epilepsies. More effort is necessary to translate
      results from basic investigations into new approaches for clinical research and
      to better understand a relationship with findings from clinical studies. The
      following report is a condensed synapsis in which molecular mechanisms of
      epileptogenesis, pharmacological modulation of epileptogenesis, evidence based
      therapy, refractoriness and prediction of outcome is provided in order to
      stimulate further collaborative international research.

PMID- 16441244
TI  - Patient satisfaction with an injection device for multiple sclerosis treatment.
AB  - OBJECTIVES: To develop a measure of treatment satisfaction assessing attributes
      specific to injected interferon-beta-1a (IFN-beta-1a) for multiple sclerosis
      (MS), and to test pain and instrument sensitivity to change among patients
      changing injection devices. MATERIALS AND METHODS: The MS Treatment Concerns
      Questionnaire (MSTCQ) was developed and tested with pain assessments before and 3
      months after patients changed devices from Rebiject to Rebiject II. RESULTS: The
      MSTCQ was organized with two domains: Injection System Satisfaction and Side
      Effects (three subscales: Injection Site Reactions, Global Satisfaction, and Flu
      Like Symptoms). Significant improvements (P = 0.002 to P < 0.001) occurred with
      the new injection device in all MSTCQ subscales (except Flu-Like Symptoms), and
      all pain measures (P < 0.0001). Clinically meaningful improvement was
      demonstrated in all scales, except Flu-Like Symptoms, by effect sizes (0.23
      0.59). CONCLUSIONS: These statistically significant and clinically meaningful
      improvements in MSTCQ and pain measures show the value of technologically
      advanced devices in domains of concern to patients.

PMID- 16441242
TI  - Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a
      family of human MAPK-specific protein tyrosine phosphatases.
AB  - Protein tyrosine phosphatases PTPN5, PTPRR and PTPN7 comprise a family of
      phosphatases that specifically inactivate MAPKs (mitogen-activated protein
      kinases). We have determined high-resolution structures of all of the human
      family members, screened them against a library of 24000 compounds and identified
      two classes of inhibitors, cyclopenta[c]quinolinecarboxylic acids and 2,5
      dimethylpyrrolyl benzoic acids. Comparative structural analysis revealed
      significant differences within this conserved family that could be explored for
      the design of selective inhibitors. PTPN5 crystallized, in two distinct crystal
      forms, with a sulphate ion in close proximity to the active site and the WPD (Trp
      Pro-Asp) loop in a unique conformation, not seen in other PTPs, ending in a 3(10)
      helix. In the PTPN7 structure, the WPD loop was in the closed conformation and
      part of the KIM (kinase-interaction motif) was visible, which forms an N-terminal
      aliphatic helix with the phosphorylation site Thr66 in an accessible position.
      The WPD loop of PTPRR was open; however, in contrast with the structure of its
      mouse homologue, PTPSL, a salt bridge between the conserved lysine and aspartate
      residues, which has been postulated to confer a more rigid loop structure,
      thereby modulating activity in PTPSL, does not form in PTPRR. One of the
      identified inhibitor scaffolds, cyclopenta[c]quinoline, was docked successfully
      into PTPRR, suggesting several possibilities for hit expansion. The determined
      structures together with the established SAR (structure-activity relationship)
      propose new avenues for the development of selective inhibitors that may have
      therapeutic potential for treating neurodegenerative diseases in the case of
      PTPRR or acute myeloblastic leukaemia targeting PTPN7.

PMID- 16441245
TI  - Effect of high-dose methylprednisolone treatment on CCR5 expression on blood
      cells in MS exacerbation.
AB  - OBJECTIVES: Therapy of acute exacerbations of multiple sclerosis (MS) with high
      dose intravenous methylprednisolone (IVMP) has shortened the recovery period
      after relapses, but the mechanisms responsible for the beneficial effects of IVMP
      in attacks have not been clearly established. Our purpose was to analyze the
      effect of IVMP on the expression of chemokine receptor 5 (CCR5) protein in blood
      in acute MS exacerbation. MATERIALS AND METHODS: Blood samples were collected
      from 10 patients with an acute MS exacerbation and the levels of CCR5 on CD4(+)
      and CD8(+) T cells and CD14(+) monocytes were analyzed by using flow cytometry
      before IVMP, 24 h, 1 and 3 weeks after commencement of treatment. RESULTS: During
      the 3-week period the percentages of CCR5-expressing CD4(+) T cells and CD8(+) T
      cells tended to decrease (P = 0.09 and 0.05, respectively), but the effect did
      not reach statistical significance. No marked changes were found in the
      percentage of CCR5-expressing CD14(+) cells. CONCLUSIONS: A tendency to a
      reduction of CCR5-expressing CD4(+) and CD8(+) blood cells induced by IVMP
      suggests inhibition of their potential to transmigrate into the central nervous
      system, which is consistent with the short-term beneficial effect of IVMP in
      acute exacerbation of MS.

PMID- 16441246
TI  - Factors affecting the quality of life in childhood epilepsy in China.
AB  - OBJECTIVES: To explore the level of, and factors affecting the quality of life
      (QOL) in childhood epilepsy in China. SUBJECTS AND METHODS: At the Peking
      University First Hospital, we consecutively identified 418 parents whose children
      were with known epilepsy to complete a questionnaire, which included children's
      demographic characteristics, clinical message of epilepsy, QOL, familial message,
      parental symptoms of anxiety/depression. RESULTS: Significant (p<0.05) affecting
      factors of children's quality of life included current educational degree, mental
      development, age at diagnosis, age at onset, seizure frequency, duration, AED
      number; parental significant (p<0.05) affecting factors included anxiety,
      depression and health. On regression analysis, parental anxiety was the most
      important factor in explaining lower QOL in childhood epilepsy. AEDs, familial
      economic state, paternal career, seizure frequency were also significant factors.
      CONCLUSION: Parental anxiety outweighed the physical factors in determining QOL
      in childhood epilepsy. Recognition of this will be helpful for professionals to
      treat disease and improve the QOL of childhood epilepsy.

PMID- 16441247
TI  - Outcome of short-term antiepileptic treatment in patients with solitary cerebral
      cysticercus granuloma.
AB  - OBJECTIVES: The duration of antiepileptic drug (AED) therapy in cases of solitary
      cerebral cysticercus granuloma (SCCG) presents a major dilemma and the efficacy
      of short-term (6 months) vs long-term (2 years) AED therapy has been studied.
      MATERIALS AND METHODS: Prospective randomized study of short-term vs long-term
      AED treatment with SCCG has been undertaken. A total of 206 subjects with new
      onset seizures with SCCG were randomized into two groups: group A (98 patients)
      were treated for 6 months and group B (108 patients) were treated for 2 years
      with AED therapy. The patients were evaluated periodically during and at least 18
      months after the tapering of drugs. RESULTS: Partial seizures with or without
      secondary generalization has been found to be the commonest manifestation
      occurring in 80.6% of patients with SCCG. In group A 66.3% and in group B 57.4%
      patients showed complete resolution of computerized tomographic lesion and rest
      had punctated residual calcification. Statistically, no significant difference in
      the recurrence of seizures was found in two groups with disappearance of lesion
      but the difference between calcified residua and complete resolution subset was
      significant. In patients having residual calcification, 42.2% in group A and
      21.7% in group B had recurrence of seizures and the difference was statistically
      significant (Z = 1.97, P < 0.05). CONCLUSIONS: The study revealed that SCCG with
      epilepsy is a benign self-limiting disease. A longer duration of therapy is not
      warranted in patients having total resolution of lesion. Calcified lesion was
      found to be the most common cause of recurrence of seizures. Higher recurrence
      rate was observed in short-term therapy in patients having calcified lesions and
      may require long-term AED treatment.

PMID- 16441248
TI  - Centralized rehabilitation after severe traumatic brain injury--a population
      based study.
AB  - OBJECTIVES: To present results from the first 3 years of centralized subacute
      rehabilitation after very severe traumatic brain injury (TBI), and to compare
      results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS:
      Prospectively, the most severely injured group of adults from an uptake area of
      2.4 million in Denmark were included at admission to a regional brain injury unit
      (BIU), on average 19 days after injury. Patients in the retrospective study used
      for comparison were randomly chosen from the national hospital register. RESULTS
      AND CONCLUSIONS: Out of 117 patients in the prospective study, six died, and 92
      (1.27 per 100,000 population per year) survived after a post-traumatic amnesia
      (PTA) period of at least 28 days. All 19 patients with PTA 7-27 days and 48% of
      survivors with PTA at least 4 weeks were discharged directly home. The incidence
      of patients vegetative at 1 month post-trauma was 0.29, and at 1 year 0.055 per
      100,000 population. By comparison of 39 patients from the centralized unit
      injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with
      similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale
      score at discharge was significantly better for the former group.

PMID- 16441249
TI  - IgM-containing fraction suppressed voltage-gated potassium channels in acquired
      neuromyotonia.
AB  - OBJECTIVES: Acquired neuromyotonia (ANM) is an autoimmune disorder caused by
      antibodies to voltage-gated potassium channels (VGKC). Previously, we reported a
      patient with immunoglobulin M (IgM), instead of immunoglobulin G (IgG), anti-VGKC
      antibody. The purpose of this study was to determine the function of IgM
      containing fraction in ANM patients. MATERIALS AND METHODS: We determined whether
      anti-VGKC antibodies in the IgG or IgM-containing fractions suppressed outward
      potassium current (OKC) using the patch clamp method in three patients with ANM.
      Whole sera from all patients suppressed OKCs. RESULT: Only the purified IgG, not
      the IgM-containing fractions from two patients suppressed VGKCs, whereas in a
      patient with IgM anti-VGKC antibody, only the IgM-containing fractions, not the
      IgG-containing fractions suppressed VGKCs. CONCLUSION: Anti-VGKC antibodies
      belonging to the IgM subclass should be determined in seronegative ANM patients.

PMID- 16441250
TI  - D-amphetamine improves cognitive deficits and physical therapy promotes fine
      motor rehabilitation in a rat embolic stroke model.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D
      amphetamine (D-amph) and physical therapy separately or combined on fine motor
      performance, gross motor performance and cognition after middle cerebral artery
      thromboembolization in rats. METHODS: Seventy-four rats were trained in
      appropriate cognitive and motor behaviours. Thirteen animals were sham-operated
      and fifty-nine animals were embolized in the right carotid territory. Animals
      were randomly assigned to five groups: 1) SHAM (non-embolized, saline), 2)
      CONTROL (embolized, saline), 3) D-AMPH (embolized, D-amph), 4) THERAPY
      (embolized, saline + physical therapy) and 5) D-AMPH + THERAPY (embolized, D-amph
      + physical therapy). Rats of the groups 4-5 underwent d-amph or saline treatment
      on days 1, 3, 5 and 7 after surgery and were re-trained for 1 h starting 60 min
      after each treatment. During this time, rats were allowed to voluntarily engage
      in suitable cognitive or motor behaviours in order to obtain food. Animals from
      all groups were re-tested during days 21-28 after surgery. RESULTS: No
      differences in infarct volumes were observed between the groups of embolized
      animals. When evaluating performances on days 21-28 after surgery, rats of the
      SHAM and THERAPY groups had better fine motor performance than those of the
      CONTROL (P < 0.05), whereas rats of SHAM and D-AMPH groups achieved better
      cognitive performance than CONTROL rats (P < 0.05). No significant differences
      were observed between any groups regarding gross motor performance. CONCLUSIONS:
      After embolization, physical therapy improved fine motor performance and D-amph
      accelerated rehabilitation of cognitive performance as observed in the rats of
      the THERAPY and D-AMPH groups. As a result of the administration of a high dose
      of D-amph, the rats of the D-AMPH + THERAPY combination group failed to engage in
      physical therapy during D-amph intoxication, thereby limiting any promotion of
      rehabilitation by combining physical therapy and D-amph.

PMID- 16441251
TI  - Headaches and the N95 face-mask amongst healthcare providers.
AB  - BACKGROUND: During the 2003 severe acute respiratory distress syndrome epidemic,
      healthcare workers mandatorily wore the protective N95 face-mask. METHODS: We
      administered a survey to healthcare workers to determine risk factors associated
      with development of headaches (frequency, headache subtypes and duration of face
      mask wear) and the impact of headaches (sick days, headache frequency and use of
      abortive/preventive headache medications). RESULTS: In the survey, 212 (47 male,
      165 female) healthcare workers of mean age 31 years (range, 21-58) participated.
      Of the 79 (37.3%) respondents who reported face-mask-associated headaches, 26
      (32.9%) reported headache frequency exceeding six times per month. Six (7.6%) had
      taken sick leave from March 2003 to June 2004 (mean 2 days; range 1-4 days) and
      47 (59.5%) required use of abortive analgesics because of headache. Four (2.1%)
      took preventive medications for headaches during this period. Multivariate
      logistic regression showed that pre-existing headaches [P = 0.041, OR = 1.97 (95%
      CI 1.03-3.77)] and continuous use of the N95 face-mask exceeding 4 h [P = 0.053,
      OR = 1.85 (95% CI 0.99-3.43)] were associated with development of headaches.
      CONCLUSIONS: Healthcare providers may develop headaches following the use of the
      N95 face-mask. Shorter duration of face-mask wear may reduce the frequency and
      severity of these headaches.

PMID- 16441252
TI  - Crossed-uncrossed difference (CUD) in a new light: anatomy of the negative CUD in
      Poffenberger's paradigm.
AB  - Crossed Uncrossed Differentials (CUDs) have long been used as surrogate for the
      interhemispheric transfer time (IHTT). Evidence is presented that macular vision
      is the province of the major hemisphere, wherein all commands are initiated
      regardless of the laterality of the effectors of such commands. Using clinical
      and time-resolved data it is shown also that the above arrangement (i.e. neural
      handedness) corresponds to the subject's behavioral avowed (avowed, self
      declared) handedness only in a statistical sense; with a substantial minority of
      humanity displaying a disparity of neural and behavioral handedness. Evidence is
      provided that the negative CUD in previously reported studies was a reflection of
      such incongruity in those subjects studied. Thus, to lateralize the command
      center it is sufficient to determine the reaction time of two symmetrically
      located effectors on the body. The side with longer reaction time is ipsilateral
      to the major hemisphere, with the difference of the two sides commensurate to
      transcallosal IHTT.

PMID- 16441253
TI  - Complete DNA sequence variation in the apolipoprotein H (beta-glycoprotein I)
      gene and identification of informative SNPs.
AB  - Apolipoprotein H (APOH), also known as beta2-glycoprotein I, is a major antigen
      for the production of antiphospholipid antibodies in autoimmune diseases.
      Previously we have examined DNA variation in the coding region of the APOH gene
      and determined the molecular basis of the common protein polymorphism. Here we
      report the results of DNA sequence variation in the entire APOH gene encompassing
      a 20.3 kb region in 46 Caucasian Americans and 48 African American chromosomes. A
      total of 150 single nucleotide polymorphisms (SNPs) and one tri-allelic
      polymorphism were identified, including 8 in the coding region, 14 in the 5'
      region and 2 in the 3'- region; the remainder were observed in introns. The
      observed number of SNPs was higher in the African American sample than in the
      Caucasian sample (130 vs. 84). We examined the race-specific linkage
      disequilibrium pattern among SNPs and identified maximally informative SNPs for
      future association studies. Altogether, we have identified 17 informative SNPs
      among Caucasians and 35 in blacks. The discovery of a full range of sequence
      variation and identification of race-specific informative SNPs in the APOH gene
      may facilitate the rapid evaluation of this variation in relation to autoimmune
      diseases.

PMID- 16441254
TI  - Haplotypes of the human RET proto-oncogene associated with Hirschsprung disease
      in the Italian population derive from a single ancestral combination of alleles.
AB  - The RET proto-oncogene is the major gene involved in the complex genetics of
      Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of
      function mutations in 15-30% of the sporadic cases. Several RET polymorphisms and
      haplotypes have been described in association with the disease, suggesting a role
      for this gene in HSCR predisposition, also in the absence of mutations in the
      coding region. Finally, the presence of a functional variant in intron 1 has
      repeatedly been proposed to explain such findings. Here we report a case-control
      study conducted on 97 Italian HSCR sporadic patients and 85 population matched
      controls, using 13 RET polymorphisms distributed throughout the gene, from the
      basal promoter to the 3'UTR. Linkage disequilibrium and haplotype analyses have
      shown increased recombination between the 5' and 3' portions of the gene and an
      over-representation, in the cases studied, of two haplotypes sharing a common
      allelic combination that extends from the promoter up to intron 5. We propose
      that these two disease-associated haplotypes derive from a single founding locus,
      extending up to intron 19 and successively rearranged in correspondence with a
      high recombination rate region located between the proximal and distal portions
      of the gene. Our results suggests the possibility that a common HSCR predisposing
      variant, in linkage disequilibrium with such haplotypes, is located further
      downstream than the previously suggested interval encompassing intron 1.

PMID- 16441255
TI  - Patterns of genetic variation in the hypertension candidate gene GRK4: ethnic
      variation and haplotype structure.
AB  - Association studies using single nucleotide polymorphisms (SNPs) have the
      potential to help unravel the genetic basis of hypertension. Nevertheless, to
      date, association studies of hypertension have yielded ambiguous results. It is
      becoming clear that such association studies must be interpreted within the
      context of the genetic structure of the populations being studied, and patterns
      of variation within specific genomic regions. With this in mind we analyzed
      genetic variation in the G protein-coupled receptor kinase 4 (GRK4) gene, a gene
      whose product has recently been shown to inhibit the dopamine receptor D1 (DRD1)
      from increasing sodium excretion. We genotyped three previously identified GRK4
      SNPs, as well as ten additional SNPs, over 71.6 kb of the GRK4 locus in four
      populations: African Americans, Asians, Hispanics and Caucasians. Haplotype
      structure varied among populations, with Hispanics and Caucasians having the most
      linkage disequilibrium (LD) among SNPs. African Americans had three shorter
      haplotype blocks, while patterns of markers in the Asian populations demonstrated
      less LD among markers, a pattern inconsistent with block structure. We observed
      limited haplotype diversity in each of the four populations, with differing
      haplotype frequencies among the ethnic groups. We also found substantial evidence
      for population differentiation, with the largest differences between the African
      American and Asian samples with F(ST) values in the upper 90(th) percentile when
      compared to a genome-wide distribution. However, for all population comparisons,
      F(ST) values decreased sharply in the 3' region of the gene. This pattern of
      differentiation among populations is consistent with selection in this part of
      the gene maintaining similar patterns of variation among otherwise divergent
      populations. Our results document not only different allele frequencies between
      populations, but differences in haplotype structure that may be important in
      evaluating association studies between hypertension and GRK4.

PMID- 16441256
TI  - High-resolution mtDNA studies of the Indian population: implications for
      palaeolithic settlement of the Indian subcontinent.
AB  - The population of the Indian subcontinent represents a very complex social and
      cultural structure. Occupying a geographically central position for the early
      modern human migrations, indications are that the founder group that migrated out
      of East Africa also reached India. In the present study we used the twin strategy
      of mapping the whole mitochondrial DNA (mtDNA) using the standard 14 restriction
      enzymes, and sequencing the non-transcribed HVSI region, to derive maximum
      maternal lineages from a sample of non-tribal Indians. The essential features of
      the reduced median network of the two datasets were the same. Both showed two
      demographic expansions of two major haplogroups, 'M' and 'N'. The reduced median
      network was drawn with inputs from other studies on the Indian population, and
      correlated with data from other ethnic populations. The coalescence time of
      expansions and genetic diversity were estimated. A reduced median network was
      also drawn combining data from studies on Africans, Southeast Asians and West
      Eurasians, tracing the migration of 'M' from East Africa to India. A time
      estimate of the migration of major mtDNA haplogroups from Africa was attempted.
      The comparison of a set of Indian maternal lineages belonging to different
      geographical regions of the country, with other populations revealed the in-situ
      differentiation and antiquity of the Indian population. Our analysis places the
      'southern route' migration as the source of haplogroup 'M'. Multiple migrations
      might have brought the other major haplogroups, 'N' and 'R', found in our sample
      to India. Archaeological evidence of modern humans in the subcontinent supports
      this mtDNA study.

PMID- 16441257
TI  - Differential distribution of human mitochondrial DNA in somatic tissues and
      hairs.
AB  - To investigate mitochondrial DNA (mtDNA) distribution within tissues during life,
      we observed length heteroplasmy in a polycytosine tract of the mitochondrial HV2
      region by size-based separation of PCR products, using a mutagenic primer which
      was designed to avoid stutter production. Blood, brain, heart, liver, skeletal
      muscle and hair shaft samples were collected during autopsies of 25 individuals.
      Here, we demonstrate differences in the level of mtDNA length heteroplasmy both
      within and between individuals and tissues. We also show that mtDNA is
      distributed randomly in varying proportions in various somatic tissues during
      growth, resulting in an imbalance in the composition of mtDNA pools among
      tissues. This mtDNA distribution appears not to be strictly random, and can be
      explained by the random somatic segregation of nucleoids. On the other hand,
      significant qualitative/quantitative mtDNA peak pattern variations in hair shafts
      are thought to be a result of the different developmental origins of hairs. Each
      hair shaft may have a restricted or clonal set of mtDNA molecules derived from a
      discrete group of stem cells.

PMID- 16441258
TI  - Golli-MBP copy number analysis by FISH, QMPSF and MAPH in 195 patients with
      hypomyelinating leukodystrophies.
AB  - The inherited disorders of CNS myelin formation represent a heterogeneous group
      of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two
      X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2,
      and the gap junction protein alpha12 (GJA12) gene in a recessive form of PMD. The
      myelin basic protein (MBP) gene, which encodes the second most abundant CNS
      myelin protein after PLP1, presents rearrangements in hypomyelinating murine
      mutants and is always included in the minimal region deleted in 18q- patients
      with an abnormal hypomyelination pattern on cerebral MRI. In this study, we
      looked at the genomic copy number at the Golli-MBP locus in 195 patients with
      cerebral MRI suggesting a myelin defect, who do not have PLP1 mutation. Although
      preliminary results obtained by FISH suggested the duplication of Golli-MBP in 3
      out of 10 patients, no abnormal gene quantification was found using Quantitative
      Multiplex PCR of Short Fluorescent fragments (QMPSF), Multiplex Amplifiable Probe
      Hybridization (MAPH), or another FISH protocol using directly-labelled probes.
      Pitfalls and interest in these different techniques to detect duplication events
      are emphasised. Finally, the study of this large cohort of patients suggests that
      Golli-MBP deletion or duplication is rarely involved in inherited defects of
      myelin formation.

PMID- 16441259
TI  - Genome-wide scan for loci influencing quantitative immune response traits in the
      Belem family study: comparison of methods and summary of results.
AB  - Here we report the results from a genome-wide linkage scan to identify genes and
      chromosomal regions that influence quantitative immune response traits, using
      multi-case leprosy and tuberculosis families from north-eastern Brazil. Total
      plasma IgE, antigen-specific IgG to Mycobacterium leprae soluble antigen (MLSA),
      M. tuberculosis soluble antigen (MTSA) and M. tuberculosis purified protein
      derivative (PPD), and antigen-specific lymphocyte proliferation (stimulation
      index or SI) and interferon-gamma (IFN-gamma) release to MLSA and PPD, were
      measured in 16 tuberculosis (184 individuals) and 21 leprosy (177 individuals)
      families. The individuals were genotyped at 382 autosomal microsatellite markers
      across the genome. The adjusted immune-response phenotypes were analysed using a
      variety of variance components and regression-based methods. These analyses
      highlighted a number of practical issues and problems with regard to
      implementation of the methods and, interestingly, differences were observed
      between several standard statistical and genetic analysis packages used. From
      this we determined that, for this set of traits in these pedigrees, significant p
      values for linkage using variance components analysis, supported by significance
      using the Visscher-Hopper modification of the Haseman-Elston method, provided the
      most compelling evidence for linkage. Using these criteria, linkage (5.8 x 10(-5)
      < p < 0.008) was seen for: total plasma IgE on chromosome 2; IgG to MLSA on
      chromosomes 8, 17 and 21; IgG to PPD on chromosome 12; SI to PPD on chromosome 1;
      IFN-gamma to MLSA on chromosomes 6, 7, 10, 12 and 14; and IFN-gamma to PPD on
      chromosomes 1, 16 and 19.

PMID- 16441260
TI  - Case-control association tests correcting for population stratification.
AB  - In case-control association studies unobserved population stratification may act
      as a confounder, leading to an increased number of false positive results.
      Methods accounting for population structure by using additional genetic markers
      broadly follow one of two concepts: Genomic Control (GC) and Structured
      Association (SA). While extending existing methods of Structured Association we
      show that it is necessary to incorporate phenotypic information when inferring
      population structure, otherwise a systematic bias is introduced. Moreover, for
      moderate population stratification a Wald test statistic should be preferred as a
      Structured Association test statistic in comparison to a likelihood ratio test.
      The introduced extensions are compared to existing methods of Structured
      Association, as well as to Genomic Control, in a simulation study which is based
      on realistic situations of large case-control studies with moderate population
      stratification. A disadvantage of Genomic Control turns out to be the large
      variation in estimating the variance inflation factor, as well as the power loss
      if population structure increases. We come to the overall conclusion that
      Structured Association, if applied correctly, is superior to Genomic Control, at
      least in the case of simple population structure as simulated here.

PMID- 16441261
TI  - Power and sample size for testing associations of haplotypes with complex traits.
AB  - Evaluation of the association of haplotypes with either quantitative traits or
      disease status is common practice, and under some situations provides greater
      power than the evaluation of individual marker loci. The focus on haplotype
      analyses will increase as more single nucleotide polymorphisms (SNPs) are
      discovered, either because of interest in candidate gene regions, or because of
      interest in genome-wide association studies. However, there is little guidance on
      the determination of the sample size needed to achieve the desired power for a
      study, particularly when linkage phase of the haplotypes is unknown, and when a
      subset of tag-SNP markers is measured. There is a growing wealth of information
      on the distribution of haplotypes in different populations, and it is not unusual
      for investigators to measure genetic markers in pilot studies in order to gain
      knowledge of the distribution of haplotypes in the target population. Starting
      with this basic information on the distribution of haplotypes, we derive analytic
      methods to determine sample size or power to test the association of haplotypes
      with either a quantitative trait or disease status (e.g., a case-control study
      design), assuming that all subjects are unrelated. Our derivations cover both
      phase-known and phase-unknown haplotypes, allowing evaluation of the loss of
      efficiency due to unknown phase. We also extend our methods to when a subset of
      tag-SNPs is chosen, allowing investigators to explore the impact of tag-SNPs on
      power. Simulations illustrate that the theoretical power predictions are quite
      accurate over a broad range of conditions. Our theoretical formulae should
      provide useful guidance when planning haplotype association studies.

PMID- 16441262
TI  - A likelihood ratio approach to family-based association studies with covariates.
AB  - We introduce a procedure for association based analysis of nuclear families that
      allows for dichotomous and more general measurements of phenotype and inclusion
      of covariate information. Standard generalized linear models are used to relate
      phenotype and its predictors. Our test procedure, based on the likelihood ratio,
      unifies the estimation of all parameters through the likelihood itself and yields
      maximum likelihood estimates of the genetic relative risk and interaction
      parameters. Our method has advantages in modelling the covariate and gene
      covariate interaction terms over recently proposed conditional score tests that
      include covariate information via a two-stage modelling approach. We apply our
      method in a study of human systemic lupus erythematosus and the C-reactive
      protein that includes sex as a covariate.

PMID- 16441263
TI  - Point mutation of an EYA1-gene splice site in a patient with oto-facio-cervical
      syndrome.
AB  - Mutations of the EYA1 gene (8q13.3) are the most common known cause of the
      branchio-oto-renal dysplasia (BOR), an autosomal dominant disease that includes
      developmental defects of branchial arch structures, middle and/or inner ear and
      kidney. The distinction between BOR and other dysplasias, such as oto-facio
      cervical syndrome (OFC), is challenged by frequent association of the former to
      other diverse malformations, and by variable expressivity even within the same
      family. OFC is characterized by trophic alterations of the facies and shoulder
      girdle in addition to the malformations seen in BOR. Recent characterization of
      one OFC patient shed some light on the controversy over whether OFC and BOR are
      the same disease, and led to the hypothesis that OFC is caused by contiguous
      deletions of EYA1 and adjacent genes. By contrast, we show here that an OFC
      patient bears a single-nucleotide substitution in a splice site of EYA1. Our
      results indicate that not only major rearrangements, but also point mutations
      altering the EYA1 reading frame, can be found in patients with OFC syndrome.

PMID- 16441264
TI  - Dear Edith Edith S. L. Gomberg, PhD January 14, 1920-January 9, 2005.

PMID- 16441265
TI  - Edith Silverglied Lisansky Gomberg, PhD 1920-2005.

PMID- 16441266
TI  - Ruminations of a Jersey boy: Ferdinand under the cork tree. 2005 Henry L. Rosett
      Award.

PMID- 16441267
TI  - Alcohol biomarker screening in medical and surgical settings.
AB  - This article highlights the proceedings of a symposium presented at the 28th
      Annual Meeting of the Research Society on Alcoholism in Santa Barbara, CA, on
      June 28, 2005, organized and chaired by Peter Miller. The presentations included
      (1) Screening for Alcohol Use Disorders in Surgical and Trauma Patients,
      presented by Claudia Spies; (2) Are Serum Levels of %CDT and GGT Related to
      Severity of Liver Biopsy Inflammation, Fibrosis, and Steatohepatitis in Patients
      with Hepatitis C? by Martin Javors; (3) Biochemical Alcohol Screening in the
      Treatment of Hypertension, presented by Peter Miller; and (4) The Cost
      Effectiveness of a New Biomarker, CDT, in a Primary Care Sample, by Michael
      Fleming. Presentations were discussed by Raymond Anton.

PMID- 16441268
TI  - Searching for the full picture: structural equation modeling in alcohol research.
AB  - This article summarizes the proceedings of a symposium presented at the 2005
      Research Society on Alcoholism meeting in Santa Barbara, California. This
      symposium begins with a description by Michael Windle of structural equation
      modeling (SEM), including the assets and liabilities of this approach. Next, Marc
      Schuckit and Tom Smith demonstrate the application of an SEM approach to
      understanding the impact of a low level of response to alcohol, using data from
      both adolescent and adult populations. Victor Hesselbrock and colleagues next
      review the results when an SEM approach is used in the longitudinal study of
      externalizing behaviors. This is followed by a description of the application of
      SEM to an affect-related model as discussed by John Kramer and Kathleen Bucholz.
      Finally, Kenneth Sher offers thoughts on how to place these findings into
      perspective.

PMID- 16441269
TI  - Understanding how the brain perceives alcohol: neurobiological basis of ethanol
      discrimination.
AB  - Understanding the neurobiological mechanisms that regulate how the brain
      perceives the intoxicating effects of alcohol is highly relevant to understanding
      the development and maintenance of alcohol addiction. The basis for the
      subjective effects of intoxication can be studied in drug discrimination
      procedures in which animals are trained to differentiate the presence of internal
      stimulus effects of a given dose of ethanol (EtOH) from its absence. Research on
      the discriminative stimulus effects of psychoactive drugs has shown that these
      effects are mediated by specific receptor systems. In the case of alcohol, action
      mediated through ionotropic glutamate, gamma-aminobutyric acid, and serotonergic
      receptors concurrently produce complex, or multiple, basis for the discriminative
      stimulus effects of EtOH. These receptor systems may contribute differentially to
      the discriminative stimulus effects of EtOH based on the EtOH dose, species
      differences, physiological states, and genetic composition of the individual. An
      understanding of the receptor mechanisms that mediate the discriminative stimulus
      effects of EtOH can be used to develop medications aimed at decreasing the
      subjective effects associated with repeated intoxication. The goal of this
      symposium was to present an overview of recent findings that highlight the
      neurobiological mechanisms of EtOH's subjective effects and to suggest the
      relevance of these discoveries to both basic and clinical alcohol research.

PMID- 16441270
TI  - BIG news in alcohol addiction: new findings on growth factor pathways BDNF,
      insulin, and GDNF.
AB  - In recent years, it has become clear that growth factors are not only critical
      for the development of the central nervous system (CNS) but may also be important
      contributors to other neuronal functions in the adult brain. This symposium,
      presented at the 2005 RSA meeting, discussed evidence to support the hypothesis
      that alterations in growth factor pathways produce dramatic changes in the
      effects of alcohol on the CNS. The 4 speakers showed that the behavioral effects
      of alcohol in the adult are regulated by 3 growth factors, insulin, glial cell
      line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor
      (BDNF). Dr. Wolf from the Heberlein laboratory presented findings obtained from
      genetic manipulations in Drosophila melanogaster, demonstrating that the insulin
      pathway controls sensitivity to the intoxicating effects of alcohol. Marian
      Logrip from the Ron and Janak laboratories presented evidence obtained in rodents
      that low concentrations of alcohol increase the expression of BDNF in the brain
      to regulate alcohol consumption. Dr. Pandey showed that amygdalar BDNF regulates
      alcohol's anxiolytic effects and preference. Finally, Dr. Janak presented
      evidence that increases in the expression of GDNF in the midbrain reduce alcohol
      self-administration in rats.

PMID- 16441272
TI  - Impact of sex: determination of alcohol neuroadaptation and reinforcement.
AB  - This article represents the proceedings of a symposium at the Research Society on
      Alcoholism meeting in Santa Barbara, California. The organizers/chairs were
      Kristine M. Wiren and Deborah A. Finn. Following a brief introduction by Deborah
      Finn, the presentations were (1) The Importance of Gender in Determining
      Expression Differences in Mouse Lines Selected for Chronic Ethanol Withdrawal
      Severity, by Kristine M. Wiren and Joel G. Hashimoto; (2) Sex Differences in
      Ethanol Withdrawal Involve GABAergic and Stress Systems, by Paul E. Alele and
      Leslie L. Devaud; (3) The Influence of Sex on Ethanol Consumption and Reward in
      C57BL/6 Mice, by Kimber L. Price and Lawrence D. Middaugh; and (4) Sex
      Differences in Alcohol Self-administration in Cynomolgus Monkeys, by Kathleen A.
      Grant.

PMID- 16441271
TI  - Actions of acute and chronic ethanol on presynaptic terminals.
AB  - This article presents the proceedings of a symposium entitled "The Tipsy
      Terminal: Presynaptic Effects of Ethanol" (held at the annual meeting of the
      Research Society on Alcoholism, in Santa Barbara, CA, June 27, 2005). The
      objective of this symposium was to focus on a cellular site of ethanol action
      underrepresented in the alcohol literature, but quickly becoming a "hot" topic.
      The chairs of the session were Marisa Roberto and George Robert Siggins. Our
      speakers were chosen on the basis of the diverse electrophysiological and other
      methods used to discern the effects of acute and chronic ethanol on presynaptic
      terminals and on the basis of significant insights that their data provide for
      understanding ethanol actions on neurons in general, as mechanisms underlying
      problematic behavioral effects of alcohol. The 5 presenters drew from their
      recent studies examining the effects of acute and chronic ethanol using a range
      of sophisticated methods from electrophysiological analysis of paired-pulse
      facilitation and spontaneous and miniature synaptic currents (Drs. Weiner,
      Valenzuela, Zhu, and Morrisett), to direct recording of ion channel activity and
      peptide release from acutely isolated synaptic terminals (Dr. Treistman), to
      direct microscopic observation of vesicular release (Dr. Morrisett). They showed
      that ethanol administration could both increase and decrease the probability of
      release of different transmitters from synaptic terminals. The effects of ethanol
      on synaptic terminals could often be correlated with important behavioral or
      developmental actions of alcohol. These and other novel findings suggest that
      future analyses of synaptic effects of ethanol should attempt to ascertain, in
      multiple brain regions, the role of presynaptic terminals, relevant presynaptic
      receptors and signal transduction linkages, exocytotic mechanisms, and their
      involvement in alcohol's behavioral actions. Such studies could lead to new
      treatment strategies for alcohol intoxication, alcohol abuse, and alcoholism.

PMID- 16441273
TI  - Predicting risky drinking outcomes longitudinally: what kind of advance notice
      can we get?
AB  - This paper summarizes the proceedings of a symposium presented at the 2005
      Research Society on Alcoholism meeting in Santa Barbara, California, that spans
      the interval from toddlerhood to early middle adulthood and addresses questions
      about how far ahead developmentally we can anticipate alcohol problems and
      related substance use disorder and how such work informs our understanding of the
      causes and course of alcohol problems and alcohol use disorder. The context of
      these questions both historically and developmentally is set by Robert Zucker in
      an introductory section. Next, Maria Wong and colleagues describe the
      developmental trajectories of behavioral and affective control from preschool to
      early adolescence in a high risk for alcoholism longitudinal study and
      demonstrate their ability to predict alcohol and drug outcomes in adolescence.
      Duncan Clark and Jack Cornelius follow with a report on the predictive utility of
      parental disruptive behavior disorders in predicting onset of alcohol problems in
      their adolescent offspring in late adolescence. Next, Kenneth Leonard and Gregory
      Homish report on adult development study findings relating baseline individual,
      spouse, and peer network drinking indicators at marriage onset that distinguish
      different patterns of stability and change in alcohol problems over the first 2
      years of marriage. In the final paper, John Schulenberg and colleagues, utilizing
      national panel data from the Monitoring the Future Study, which cover the 18- to
      35-year age span, show how trajectories of alcohol use in early adulthood predict
      differential alcohol abuse and dependence outcomes at age 35. Finally, Robert
      Zucker examines the degree to which the core symposium questions are answered and
      comments on next step research and clinical practice changes that are called for
      by these findings.

PMID- 16441274
TI  - Smoking comorbidity in alcoholism: neurobiological and neurocognitive
      consequences.
AB  - Considerable research attests to the adverse effects of chronic smoking on
      cardiac, pulmonary, and vascular function as well as on increased risk for
      various cancers. However, comparatively little is known about the effects of
      chronic smoking on brain function. Although smoking rates have decreased in the
      developed world (they have increased in the developing world), smoking rates have
      been at a persistently high level in individuals with alcohol use disorders.
      Despite the high prevalence of comorbid chronic smoking and alcohol dependence,
      very few studies have addressed the separate and interactive effects that smoking
      and alcoholic drinking may have on neurobiology and brain function. This
      symposium, which took place at the annual meeting of the Research Society on
      Alcoholism in Santa Barbara, California, on June 29, 2005, postulates that the
      neurobiologic and neurocognitive abnormalities commonly described in studies of
      alcohol-dependent individuals are modulated by concurrent abuse of tobacco
      products and that brain recovery in abstinent alcoholic individuals is affected
      by chronic smoking. Four expert speakers and a discussant from different research
      disciplines focus in this symposium on the description of neurobiological and
      neurobehavioral effects because of concomitant drinking and smoking.
      Understanding the potential separate effects and interactions of chronic
      nicotine/smoking and alcohol consumption promotes a better understanding of
      specific mechanisms and neurocognitive consequences of brain injury and brain
      recovery with abstinence. The material presented contributes useful information
      to ongoing discussions about treatment strategies for these comorbid disorders
      and valuable educational material that can be used to affect public perception
      about smoking and perhaps health policy.

PMID- 16441275
TI  - Multidisciplinary perspectives on impaired control over substance use.
AB  - This article presents the proceedings of a symposium held at the June 2005
      meeting of the Research Society on Alcoholism in Santa Barbara, California.
      Impaired control over substance use has long been considered a central feature of
      alcohol and drug dependence. However, much remains to be learned about the nature
      of impaired control, the mechanisms by which acute and chronic substance use can
      lead to impaired control, and how this construct is best assessed in the
      laboratory and the clinic. The goal of this symposium was to describe current
      perspectives on impaired control over alcohol and drug use from diverse research
      areas, to promote future multidisciplinary work in this area. Four speakers
      described their work on impaired control using human clinical samples (Dr.
      Chung), animal models (Dr. Miczek), experimental laboratory paradigms in humans
      (Dr. Fillmore), and neuroimaging studies (Dr. Easdon). Taken together, the talks
      highlighted the heterogeneous nature of constructs such as impaired inhibitory
      control, and patterns of impulsive and compulsive substance use. Future clinical
      and experimental research should attempt to carefully define and measure
      particular aspects of impaired control and to seek insights from other
      disciplines.

PMID- 16441276
TI  - Advances in the pharmacotherapy of alcoholism: challenging misconceptions.
AB  - This article highlights the proceedings of a symposium presented at the 28th
      Annual Scientific Meeting of the Research Society on Alcoholism in Santa Barbara,
      CA, June 27, 2005. The organizer and chair was Henry R. Kranzler. The
      presentations included: (1) Introduction, by Henry R. Kranzler; (2) Neurobiology
      of Alcohol Dependence: Implications for Medical Treatment, by George Koob; (3)
      Advances in Alcoholism Pharmacotherapy, by Henry R. Kranzler; (4) Patient
      Acceptance of Alcoholism Pharmacotherapy, by David R. Gastfriend; (5) System
      Challenges in the Adoption of Pharmacotherapy, by Robert M. Swift; and (6)
      Pharmacotherapy for Alcohol Dependence: Strengths, Challenges, and Future
      Directions, by Mark L. Willenbring.

PMID- 16441278
TI  - Addressing substance abuse in health care settings.
AB  - This article summarizes the proceedings of a roundtable discussion at the 2005
      annual meeting of the Research Society on Alcoholism in Santa Barbara,
      California. The chair was William R. Miller. The presentations were as follows:
      (1) Screening and Brief Intervention for Alcohol Problems, by Allen Zweben; (2)
      Three Intervention Models and Their Impact on Medical Records, by Denise Ernst;
      (3) Pharmacotherapies for Managing Alcohol Dependence in Health Care Settings, by
      Roger D. Weiss; (4) The Trauma Center as an Opportunity, by Carol R. Schermer;
      (5) Motivational Interviewing by Telephone and Telemedicine, by Catherine Baca;
      (6) Health Care as a Context for Treating Drug Abuse and Dependence, by Wilson M.
      Compton; and (7) Interventions for Heavy Drinking in Health Care settings:
      Barriers and Strategies, by Mark L. Willenbring.

PMID- 16441277
TI  - Capturing the moment: innovative approaches to daily alcohol assessment.
AB  - This article is a summary of a symposium presented at the 2005 Research Society
      on Alcoholism annual conference organized by Dan J. Neal and chaired by William
      R. Corbin. Event-level data, wherein each "event" (e.g., day) is captured as its
      own data point, capture the complex patterns of drinking and other high-risk
      behaviors in ways that the typical aggregate approach cannot. Because of their
      richness, methodologies that incorporate event-level data are becoming more
      common in alcohol research. At least 3 distinct forms of event-level data can be
      gathered: retrospective data (those collected on a single occasion, using memory
      aids to help each participant reconstruct all drinking events over a specific
      period of time), daily monitoring data (reporting on all events for that day),
      and momentary assessment (those recorded immediately following a drinking event
      or in response to a prompt from researchers). The goal of this symposium was to
      address many issues associated with event-level methodology, as well as
      demonstrate projects that are currently implementing such innovative data
      collection. The 4 presentations included in this symposium were "Realizing the
      Promise and Avoiding the Pitfalls of Retrospective Daily Estimation Assessments
      of Alcohol Use" by Frances K. Del Boca; "Using Interactive Voice Response
      Technology to Assess the Alcohol-Victimization Link" by Kathleen Parks, Linda
      King, and Ann Pardi; "Methodological Issues in Using Personal Data Assistants to
      Self-monitor Alcohol Consumption" by R. Lorraine Collins, Mark Muraven, and
      Charlene Vetter; and "Collecting Event-level Data Using the World Wide Web" by
      Dan J. Neal and Kim Fromme.

PMID- 16441280
TI  - Long-term posttreatment functioning among those treated for alcohol use
      disorders.
AB  - This article summarizes the proceedings of a symposium that was organized and
      chaired by Patrick R. Clifford and presented at the 2005 Research Society on
      Alcoholism meeting in Santa Barbara, California. The aims of the presentation
      were to focus on the prediction and explanation of longer-term functioning
      following alcohol use disorders (AUD) treatment. Along these lines, Stephen A.
      Maisto, PhD, presented data (i.e., Project MATCH outpatient sample) on the
      relationship between drinking behavior in the first year following AUD outpatient
      treatment initiation and functioning at 3-year follow-up. Robert L. Stout, PhD,
      using data from the Extended Case Monitoring Study, analyzed long-term drinking
      patterns using shorter-term information. James R. McKay, PhD, examined the
      relationship between treatment services received and problem severities across a
      2-year follow-up period. J. Scott Tonigan, PhD, served as the panel discussant.

PMID- 16441279
TI  - Should DSM-V include dimensional diagnostic criteria for alcohol use disorders?
AB  - This program calls attention to the upcoming timetable for the revision of the
      Diagnostic and Statistical Manual (DSM)-IV and the publication of DSM-V. It is
      vitally important for Research Society of Alcoholism members to be aware of the
      current discussions of the important scientific questions related to the next DSM
      revision and to use the opportunity for input. The title of the symposium
      highlights 1 key question, i.e., whether the DSM definitions should remain
      strictly categorical as in the past or whether a dimensional component should be
      included in this revision. Two substantive and 1 conceptual paper are included in
      this portion of the symposium. The fourth and final presentation detailing the
      revision timetable and the opportunities for input is by Dr. Darrel Regier. Dr.
      Regier is the director of American Psychiatric Institute for Research and
      Education the research and education branch of the American Psychiatric
      Association and the organization within the APA that will oversee the DSM
      revision. The discussion is by Marc Schuckit, who was chair of the Substance Use
      disorders (SUD) Committee for DSM-IV and cochair of the international group of
      experts reviewing the SUD definitions for DSM-V.

PMID- 16441281
TI  - The search for new ways to change implicit alcohol-related cognitions in heavy
      drinkers.
AB  - This article summarizes a symposium on new ways to change implicit alcohol
      related cognitions, presented at the 2005 Annual Meeting of the Research Society
      on Alcoholism in Santa Barbara, California, organized by Wiers and Cox. During
      the past few years, research has demonstrated that implicit cognitions predict
      unique variance in prospective alcohol use and preliminary results indicate that
      they also predict treatment outcomes. The central question in this symposium was
      how implicit cognitions can be changed and how the changes will influence
      behavior. Field presented data showing that an attentional bias for alcohol can
      be altered by attentional training: heavy drinkers who were trained not to attend
      to alcohol stimuli reported less craving and drank less beer than those trained
      to attend to alcohol stimuli. Schoenmakers used a similar, clinically relevant
      attentional retraining (AR) procedure, heavy drinkers were trained not to attend
      to alcohol pictures or received no training. After the training, the AR group
      attended less to the alcohol pictures than the control group. Fadardi described
      the Alcohol Attentional Control Training Program (AACTP), which makes alcohol
      drinkers aware of the automatic, cognitive determinants of their drinking and
      aims to help them to gain control over these processes. Data were presented to
      support the effectiveness of the AACTP. Palfai presented data showing that
      alcohol drinkers can be taught to use implementation intentions to gain control
      over their drinking, which may be used to automatically activate self-control
      skills in the presence of alcohol cues. In his discussion, Stacy pointed out the
      importance of recent cognitive theories that integrate attention and memory
      processes-theories that can help us better understand the mechanisms involved in
      AR. Together, the studies presented demonstrate that there are promising new ways
      in which implicit alcohol-related cognitions and their effects on drinking can be
      changed. After further refinement, these procedures might be used in clinical
      interventions that have not previously addressed implicit cognitive processes.

PMID- 16441282
TI  - Challenges applying alcohol brief intervention in diverse practice settings:
      populations, outcomes, and costs.
AB  - This article summarizes the proceedings of a symposium at the 2005 Research
      Society on Alcoholism, Santa Barbara, California. The purpose of the symposium
      was to address challenges that arise in translating evidence for efficacy of
      alcohol brief intervention (BI) into diverse clinical settings and populations by
      reviewing the literature and describing 4 research studies. Dr. Saitz reviewed
      the limitations in evidence for efficacy of BIs and then described results of a
      randomized clinical trial of brief motivational intervention for medical
      inpatients drinking risky amounts. Dr. Svikis presented alternative methods for
      identifying pregnant women in prenatal care at risk for alcohol and drug problems
      (including nicotine and caffeine) and BIs to reduce or eliminate use. Dr.
      D'Onofrio discussed results of a randomized trial of the brief negotiated
      interview in emergency department patients. Dr. Kraemer presented results of a
      decision analytic and computer-simulation model regarding the cost-effectiveness
      of alcohol screening and intervention in primary care settings. Finally, Dr. Perl
      discussed the salient issues and suggested future directions for work in the area
      of alcohol BI.

PMID- 16441283
TI  - Understanding alcohol expectancy effects: revisiting the placebo condition.
AB  - This article summarizes a symposium organized and cochaired by Maria Testa and
      presented at the 2005 Annual Meeting of the Research Society on Alcoholism, in
      Santa Barbara, California. The symposium explored issues relevant to
      understanding the function of placebo conditions and to interpreting placebo
      effects. Cochair Mark Fillmore began with an overview of the use of placebo
      conditions in alcohol research, focusing on methodological issues. Jeanette
      Norris and her colleagues conducted a review of studies examining placebo
      conditions among women. They conclude that expectancy effects are limited to a
      few domains. Maria Testa and Antonia Abbey presented papers suggesting that
      placebo manipulations may result in unanticipated compensatory effects in actual
      or hypothetical social situations. That is, placebo participants may compensate
      for anticipated cognitive impairment through vigilant attention to situational
      cues. John Curtin's research suggests that the compensatory strategies of placebo
      participants appear to involve a sensitization of evaluative control, resulting
      in improved performance. Kenneth Leonard provided concluding remarks on the
      meaning of placebo effects and the value of placebo conditions in research.

PMID- 16441285
TI  - From blue states to up states: a regional view of NMDA-ethanol interactions.
AB  - This article summarizes the proceedings of a symposium at the 2005 Research
      Society on Alcoholism Meeting in Santa Barbara, California, organized and
      cochaired by John J. Woodward and Dorit Ron. The purpose of the symposium was to
      discuss recent findings that extend our understanding of the importance of the N
      methyl-D-aspartate (NMDA) receptor as a target for ethanol action in the brain.
      These receptors are ligand-gated ion channels that are activated by the
      neurotransmitter glutamate and are critically involved in many forms of synaptic
      plasticity including those associated with learning and memory. In the first
      presentation, Dorit Ron presented data showing how activation of Fyn or Src
      tyrosine kinases differentially regulated the cell surface expression and
      activity of NR2A and NR2B containing NMDA receptors. Danny Winder discussed the
      effects of ethanol on NMDA receptor-dependent long-term potentiation in the bed
      nucleus of the stria terminalis (BNST), a brain region associated with the
      interaction between stress and drug/alcohol use. In the third presentation,
      Marisa Roberto described adaptations in the expression and function of NMDA
      receptors in the central nucleus of the amygdala following chronic exposure to
      ethanol. Finally, John Woodward described the effects of ethanol on the activity
      of neurons in deep layers of the prefrontal cortex using a novel slice coculture
      preparation.

PMID- 16441284
TI  - Effects of ethanol on adenosine 5'-triphosphate-gated purinergic and 5
      hydroxytryptamine receptors.
AB  - This report of the proceedings of a symposium presented at the 2005 annual
      meeting of the Research Society on Alcoholism highlights the actions of ethanol
      on purinergic (P2XRs) and 5-hydroxytryptamine3 (5-HT3Rs) receptors. Both P2XRs
      and 5-HT3Rs, are modulated by pharmacologically relevant concentrations of
      ethanol, with inhibition or stimulation of P2XR subtypes and stimulation of 5
      HT3Rs, respectively. With regard to ethanol-modulatory actions, these 2
      distinctly different receptor classes have been studied to a much lesser extent
      than other LGICs. The organizers and chairs were Daryl L. Davies and Tina K.
      Machu. John J. Woodward discusses the molecular pharmacology and physiology of
      P2XRs and 5-HT3Rs and sets the stage for a detailed investigation into the
      ethanol sensitivity of these channels by the invited speakers. Daryl L. Davies
      discusses the results from recent electrophysiological studies conducted in his
      and Dr. Woodward's laboratories, highlighting the actions of ethanol on P2XR
      subtypes. Jiang-Hong Ye discusses results from recent studies using loose-patch
      and whole-cell recordings on purinergic receptors expressed on neurons from the
      ventral tegmental area (VTA) in rats. Tina K. Machu discusses
      electrophysiological studies conducted in her and Dr. David Lovinger's
      laboratories on nonpore lining residues of the second transmembrane domain (TM2)
      of the 5-HT3A receptor. Li Zhang presents data demonstrating that F-actin
      cytoskeletons play a critical role in 5-HT3 receptor clustering in hippocampal
      neurons. Collectively, the presentations provided strong evidence that P2X and 5
      HT3 receptors are important targets for ethanol action.

PMID- 16441287
TI  - Female offspring of alcoholic individuals: recent findings on alcoholism and
      psychopathology risks: symposium presented at the Research Society on Alcoholism,
      2004, Vancouver Aruna Gogineni, Chair.

PMID- 16441289
TI  - Combination of multiple microsatellite data sets to investigate genetic diversity
      and admixture of domestic cattle.
AB  - Microsatellite markers are commonly used for population genetic analyses of
      livestock. However, up to now, combinations of microsatellite data sets or
      comparison of population genetic parameters from different studies and breeds has
      proven difficult. Often different genotyping methods have been employed,
      preventing standardization of microsatellite allele calling. In other cases
      different sets of markers have been genotyped, providing differing estimates of
      population genetic parameters. Here, we address these issues and illustrate a
      general two-step regression approach in cattle using three different sets of
      microsatellite data, to combine population genetics estimates of diversity and
      admixture. This regression-based method is independent of the loci genotyped but
      requires common breeds in the data sets. We show that combining microsatellite
      data sets can provide new insights on the origin and geographical distribution of
      genetic diversity and admixture in cattle, which will facilitate global
      management of this livestock species.

PMID- 16441290
TI  - Genomic structure and gene order of swine chromosome 7q1.1-->q1.2.
AB  - To clarify the structure of the porcine genomic region that contains quantitative
      trait loci (QTL) related to fat, we constructed a bacterial artificial chromosome
      (BAC) contig of the region from DST to SRPK1 on porcine chromosome 7 and
      performed low-redundancy 'skim' shotgun sequencing of the clones that composed a
      minimum tiling path of the contig. This analysis revealed that the gene order
      from VPS52 to SRPK1 is conserved between human and swine and that comparison with
      the human sequence identified a rearrangement in the swine genome at the proximal
      end of VPS52. Analysis of the nucleotide sequences of three BAC clones that
      included the rearrangement point demonstrated that COL21A1 and DST, which were
      not present in the corresponding human region, were located adjacent to the
      rearrangement point. These results provide useful information about the genomic
      region containing QTL for fat in pigs and help to clarify the structure of the so
      called 'extended-class II' region distal to the porcine major histocompatibility
      complex class II region.

PMID- 16441286
TI  - Structural and functional modifications in glutamateric synapses following
      prolonged ethanol exposure.
AB  - This article summarizes the proceedings of a symposium presented at the 2005
      annual meeting of the Research Society on Alcoholism in Santa Barbara,
      California, USA. The organizer and chair was L. Judson Chandler. The
      presentations were (1) Chronic Ethanol Exposure, N-Methyl-D-Aspartate (NMDA)
      Receptor Dynamics, and Withdrawal Hyperexcitability, by Adam Hendricson, Regina
      Maldve, and Richard Morrisett; (2) Ethanol-Induced Synaptic Targeting of NMDA
      Receptors Is Associated With Enhanced Postsynaptic Density-95 Clustering and
      Spine Size, by Judson Chandler and Ezekiel Carpenter-Hyland; (3) Presynaptic and
      Postsynaptic Alterations in the Nucleus Accumbens Following Chronic Alcohol
      Exposure, by Feng Zhou, Youssef Sari, and Richard Bell; and (4) An Active Role
      for Accumbens Homer2 Expression in Alcohol-Induced Neural Plasticity, by Karen
      Szumlinski.

PMID- 16441292
TI  - Malic enzyme 1 genotype is associated with backfat thickness and meat quality
      traits in pigs.
AB  - Malic enzyme 1 (ME1) is a part of the tricarboxylate shuttle that provides NADPH
      and acetyl-CoA required in fatty acid biosynthesis. The pig ME1 locus maps on the
      proximal end of chromosome 1, where a quantitative trait loci (QTL) affecting fat
      deposition has been previously described. We amplified fragments of 1457 and 1459
      bp that corresponded to the complete coding region and the 3'-untranslated region
      (UTR), respectively, of the pig ME1 gene. The sequences of these two fragments in
      pigs from three breeds (Landrace, Large White and Pietrain) contained five single
      nucleotide polymorphisms (SNP) in the 3'-UTR: C1706T, G1762T, A1807C, C1857A and
      T1880A. Three haplotypes were found in two generations of a selected Landrace
      population: H1 (C1706 G1762 A1807 C1857 A1880), H2 (C1706 G1762 A1807 C1857
      T1880) and H3 (T1706 T1762 C1807 A1857 T1880). Using Bayesian association
      analyses, significant associations (highest posterior density at 95%) between ME1
      genotype and backfat (BF) thickness at 171 days and muscular pH were found in a
      Landrace population.

PMID- 16441291
TI  - A genome scan for loci affecting pork quality in a Duroc-Landrace F population.
AB  - A genome scan was conducted on 370 F2 Duroc-Landrace pigs. Microsatellite markers
      (n = 182) were genotyped across the entire F2 population, all F1 parents and the
      paternal grandparents. Breed of origin of all chromosomal segments inherited in
      F2 progeny were predicted using GenoProb, where genotypic data, genetic maps and
      extended pedigrees were used as inputs. Statistical tests for quantitative trait
      loci (QTL) associations were conducted on 41 phenotypes with SAS using output
      from GenoProb for genotypic data. Fixed effects included sex and age at
      slaughter. For certain analyses carcass weight, RYR1 genotype and/or PRKAG3
      genotype were also included as covariates. Subjective and objective measures of
      pork colour, marbling and tenderness were recorded, as well as measures of
      carcass fatness and muscularity. Test results were adjusted to a genome-wide
      level of significance. Five genomic regions presented significant evidence for
      QTL at chromosome 1 positions 6 cM (intramuscular fat) and 67 cM (Hunter L*),
      chromosome 2 position 62 cM (taste panel tenderness), chromosome 17 position 50
      (loineye area and image analysis estimated loineye area) and X position 87 cM
      (carcass weight). Sixty-six suggestive associations were detected. Fourteen of
      these associations were within the regions with significant QTL on chromosomes 2,
      17 and X, and the remaining 52 associations resided in 29 other regions on 13
      different chromosomes of the porcine genome. The chromosome 2 region of 60-66 cM
      was associated with all measures of pork tenderness and the region on chromosome
      17 (32-39 cM) was associated with both measures of intramuscular fat and loineye
      area. After verification, the QTL for marbling and tenderness should be useful in
      commercial production to improve pork quality as the population was developed
      from two of the three most utilized breeds of swine in the USA.

PMID- 16441293
TI  - Genetic diversity among horse populations with a special focus on the Franches
      Montagnes breed.
AB  - Genetic characterization helps to assure breed integrity and to assign
      individuals to defined populations. The objective of this study was to
      characterize genetic diversity in six horse breeds and to analyse the population
      structure of the Franches-Montagnes breed, especially with regard to the degree
      of introgression with Warmblood. A total of 402 alleles from 50 microsatellite
      loci were used. The average number of alleles per locus was significantly lower
      in Thoroughbreds and Arabians. Average heterozygosities between breeds ranged
      from 0.61 to 0.72. The overall average of the coefficient of gene differentiation
      because of breed differences was 0.100, with a range of 0.036-0.263. No
      significant correlation was found between this parameter and the number of
      alleles per locus. An increase in the number of homozygous loci with increasing
      inbreeding could not be shown for the Franches-Montagnes horses. The proportion
      of shared alleles, combined with the neighbour-joining method, defined clusters
      for Icelandic Horse, Comtois, Arabians and Franches-Montagnes. A more disparate
      clustering could be seen for European Warmbloods and Thoroughbreds, presumably
      from frequent grading-up of Warmbloods with Thoroughbreds. Grading-up effects
      were also observed when Bayesian and Monte Carlo resampling approaches were used
      for individual assignment to a given population. Individual breed assignments to
      defined reference populations will be very difficult when introgression has
      occurred. The Bayesian approach within the Franches-Montagnes breed
      differentiated individuals with varied proportions of Warmblood.

PMID- 16441295
TI  - Radiation hybrid mapping of all 10 characterized bovine Toll-like receptors.
AB  - Toll-like receptors (TLRs) are cell-surface signalling molecules that recognize a
      range of highly conserved pathogen molecules and instigate the appropriate immune
      response. Here, we report the mapping of all 10 characterized bovine TLR genes
      using a radiation hybrid panel. The genomic organization of the bovine TLRs is
      similar to that of humans and mice. TLR1, TLR6 and TLR10 map closely together on
      Bos taurus chromosome 6 (BTA6), while TLR7 and TLR8 map to the X chromosome.
      TLR2, TLR3, TLR4, TLR5 and TLR9 map to BTA17, BTA27, BTA8, BTA16 and BTA22
      respectively. Our increased knowledge of the genomic organization of the bovine
      TLR genes may promote our understanding of their evolution and help in the
      identification of bovine genes underlying disease-resistance traits.

PMID- 16441294
TI  - Exploration of genes showing intramuscular fat deposition-associated expression
      changes in musculus longissimus muscle.
AB  - Marbling, as defined by the amount of intramuscular fat, is an economically
      important trait in beef cattle. Intramuscular fat deposition is postulated to
      arise mainly from a series of adipogenic events in intramuscular adipocyte
      lineage cells and in the physiological or anatomical milieux surrounding them.
      This study was designed to investigate gene-expression patterns associated with
      fat deposition in musculus longissimus muscle, including adipocyte-lineage cells
      and part of the milieux. Differential-display PCR (ddPCR) was used to examine
      expression differences between low-marbled and high-marbled steer groups at 8,
      10, 12 and 14 months of age, encompassing the time that marbling starts to
      appear. Seventy-four of 2114 total bands on ddPCR gel-bands were significant (P <
      0.05) for the group effect, the interaction effect between group and age, or both
      the group and the interaction effects. Sequence analysis of 72 of these bands
      revealed 77 genes, including 35 annotated genes and 42 novel sequences. Among the
      35 annotated genes, 6 (BTG2, PDHB, SORBS1, TRDN, TTN and MGP) have been related
      to changes in intramuscular fat deposition, possibly by exerting effects on
      adipocyte-lineage cells or on the milieux surrounding them.

PMID- 16441296
TI  - Mapping of quantitative trait loci for carcass traits in a Japanese Black (Wagyu)
      cattle population.
AB  - To detect quantitative trait loci (QTL) that influence economically important
      traits in a purebred Japanese Black cattle population, we performed a preliminary
      genome-wide scan using 187 microsatellite markers across a paternal half-sib
      family composed of 258 offspring. We located six QTL at the 1% chromosome-wise
      level on bovine chromosomes (BTA) 4, 6, 13, 14 and 21. A second screen of these
      six QTL regions using 138 additional paternal offspring half-sib from the same
      sire, provided further support for five QTL: carcass weight on BTA14 (22-39 cM),
      one for rib thickness on BTA6 (27-58 cM) and three for beef marbling score (BMS)
      on BTA4 (59-67 cM), BTA6 (68-89 cM) and BTA21 (75-84 cM). The location of QTL for
      subcutaneous fat thickness on BTA13 was not supported by the second screen (P >
      0.05). We determined that the combined contribution of the three QTLs for BMS was
      10.1% of the total variance. The combined phenotypic average of these three Q was
      significantly different (P < 0.001) from those of other allele combinations.
      Analysis of additional half-sib families will be necessary to confirm these QTL.

PMID- 16441297
TI  - An effect of a missense mutation in the porcine melanocortin-4 receptor (MC4R)
      gene on production traits in Polish pig breeds is doubtful.
AB  - A missense G-A SNP in the porcine melanocortin-4 receptor (MC4R) gene that causes
      an Asp-Asn substitution at position 298 of the corresponding MC4R protein is
      considered to be economically important, although published results on its effect
      are inconsistent. We analysed the association of this MC4R polymorphism with
      production traits in 679 gilts from two breeds, Polish Large White (PLW) and
      Polish Landrace (PL), as well as one synthetic line 990. The frequency of the A
      allele differed significantly among the breeds with frequencies of 0.76, 0.29 and
      0.16 in PLW, PL and line 990 respectively. There was no evidence of an effect of
      this polymorphism on daily food intake, backfat thickness or abdominal fat. The A
      allele was correlated with higher test daily gains and lower levels of
      intramuscular fat in PL, and increased levels of intramuscular fat in PLW.

PMID- 16441298
TI  - An integrated radiation hybrid map of bovine chromosome 18 that refines a
      critical region associated with multiple ocular defects in cattle.
AB  - Congenital multiple ocular defects (MOD) of Japanese black cattle is a hereditary
      ocular disorder with an autosomal recessive mode of inheritance showing
      developmental defects of the lens, retina and iris, persistent embryonic eye
      vascularization and microphthalmia. The MOD locus has been mapped by linkage
      analysis to a 6.6-cM interval on the proximal end of bovine chromosome 18, which
      corresponds to human chromosome 16q and mouse chromosome 8. To refine the MOD
      region in cattle, we constructed an integrated radiation hybrid (RH) map of the
      proximal region of bovine chromosome 18, which consisted of 17 genes and 10
      microsatellite markers, using the SUNbRH7000 panel. Strong conservation of gene
      order was found among the corresponding chromosomal regions in cattle, human and
      mouse. The MOD-critical region was fine mapped to a 59.5-cR region that
      corresponds to a 6.3-Mb segment of human chromosome 16 and a 4.8-Mb segment of
      mouse chromosome 8. Several positional candidate genes, including FOXC2 and
      USP10, were identified in this region.

PMID- 16441299
TI  - Mapping of genes expressed in activated porcine Peyer's patch.
AB  - To determine the chromosomal locations for genes expressed in porcine Peyer's
      patches, polymerase chain reaction-based mapping of expressed sequence tags
      (ESTs) isolated from a porcine Peyer's patch-specific cDNA library was performed
      across a 6500-rad swine radiation hybrid panel. A total of 116 ESTs were mapped
      with LOD scores >6.0, and another 11 ESTs had LOD scores between 5.0 and 6.0. Of
      these 127 ESTs, 63% matched known genes (<e-25), 26% matched genes of unknown
      function, and 11% matched no sequences in the public mammalian databases.
      Comparative mapping information for 91% of the unknown ESTs was obtained in
      silico by sequence matching to human chromosomes. Placement of these ESTs on the
      porcine map will assist in the development of high density and comparative
      genetic maps for positional cloning and identification of genes responsible for
      immune function in the gut.

PMID- 16441300
TI  - A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes
      hereditary chondrodysplasia in sheep.
AB  - Ovine hereditary chondrodysplasia, or spider lamb syndrome (SLS), is a genetic
      disorder that is characterized by severe skeletal abnormalities and has resulted
      in substantial economic losses for sheep producers. Here we demonstrate that a
      non-synonymous T>A transversion in the highly conserved tyrosine kinase II domain
      of a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3), is
      responsible for SLS. We also demonstrate that the mutant FGFR3 allele has an
      additive effect on long-bone length, calling into question the long-standing
      belief that SLS is inherited as a strict monogenic, Mendelian recessive trait.
      Instead, we suggest that SLS manifestation is determined primarily by the
      presence of the mutant FGFR3 allele, but it is also influenced by an animal's
      genetic background. In contrast to FGFR3 mutations causing dwarfism in humans,
      this single-base change is the only known natural mutation of FGFR3 that results
      in a skeletal overgrowth phenotype in any species.

PMID- 16441301
TI  - Chromosomal localization of the UBAP2Z and UBAP2W genes in chicken.

PMID- 16441302
TI  - Mapping of the CCK, PSMC2, PSMC4, PSMD1, CPB1 and PSPH genes in cattle.

PMID- 16441303
TI  - Construction of a normalized Bos taurus and Bos indicus macrophage-specific cDNA
      library.

PMID- 16441304
TI  - Radiation hybrid mapping of seven bovine genes encoding transcription factors
      involved in adipogenesis.

PMID- 16441305
TI  - Sequencing, mapping and nucleotide variation of porcine coat colour genes EDNRB,
      MYO5A, KITLG, SLC45A2, RAB27A, SILV and MITF.

PMID- 16441306
TI  - Full-length cDNA, molecular characterization and physical mapping of five genes
      from a porcine fetal cDNA library.

PMID- 16441307
TI  - Assignment of turkey linkage group M22 to the comparative turkey/chicken map.

PMID- 16441308
TI  - Analysis of chicken embryonic gonad expressed sequenced tags.

PMID- 16441309
TI  - Canine microsatellites associated with genes implicated in cardiac development
      and function.

PMID- 16441310
TI  - Exclusion of CXCR4 as the cause of trapped neutrophil syndrome in Border Collies
      using five microsatellites on canine chromosome 19.

PMID- 16441312
TI  - Meeting the needs of simulated patients and caring for the person behind them?

PMID- 16441313
TI  - Critical friendship.

PMID- 16441314
TI  - Face validity of assessments: faith-based interpretations or evidence-based
      science?

PMID- 16441315
TI  - Primary care is dying in the United States: mutatis mutandis.

PMID- 16441316
TI  - Is bedside teaching in cardiology necessary for the undergraduate education of
      medical students?

PMID- 16441317
TI  - In-training assessment (ITA): designing the whole to be greater than the sum of
      the parts.

PMID- 16441318
TI  - Correspondence course--advice on writing for Medical Education's Letters section.

PMID- 16441319
TI  - Relationship of resident characteristics, attitudes, prior training and clinical
      knowledge to communication skills performance.
AB  - PURPOSE: A substantial body of literature demonstrates that communication skills
      in medicine can be taught and retained through teaching and practice.
      Considerable evidence also reveals that characteristics such as gender, age,
      language and attitudes affect communication skills performance. Our study
      examined the characteristics, attitudes and prior communication skills training
      of residents to determine the relationship of each to patient-doctor
      communication. The relationship between communication skills proficiency and
      clinical knowledge application (biomedical and ethical) was also examined through
      the use of doctor-developed clinical content checklists, as very little research
      has been conducted in this area. METHODS: A total of 78 first- and second-year
      residents across all departments at Dalhousie Medical School participated in a
      videotaped 4-station objective structured clinical examination presenting a range
      of communication and clinical knowledge challenges. A variety of instruments were
      used to gather information and assess performance. Two expert raters evaluated
      the videotapes. RESULTS: Significant relationships were observed between resident
      characteristics, prior communication skills training, clinical knowledge and
      communication skills performance. Females, younger residents and residents with
      English as first language scored significantly higher, as did residents with
      prior communication skills training. A significant positive relationship was
      found between the clinical content checklist and communication performance.
      Gender was the only characteristic related significantly to attitudes.
      CONCLUSIONS: Gender, age, language and prior communication skills training are
      related to communication skills performance and have implications for resident
      education. The positive relationship between communication skills proficiency and
      clinical knowledge application is important and should be explored further.

PMID- 16441320
TI  - The risks and benefits of being a young female adolescent standardised patient.
AB  - OBJECTIVE: To follow the progress of young female adolescents, as risk-taking
      standardised patients (SPs), and to monitor for adverse affects that role-playing
      may have on the adolescents. METHODS: A prospective design was used in which 11
      female adolescents, aged 13-15 years, were recruited from 2 schools. The
      adolescents were trained to portray risk-taking individuals with a medical
      condition and were interviewed with their SP mother by final-year medical
      students 1-3 times a month over 6-14 months. A control group was selected from
      both schools (n = 6). Main outcome measures were pre- and post-interviews using
      standardised questionnaires [Achenbach's Youth Self-Report (YSR) and Piers Harris
      Children's Self Concept Scale (SCS),] and focus groups. RESULTS: The adolescent
      group simulated 111 interviews (mean per adolescent 10.1, SD = 6.2) each lasting
      60-70 minutes. QUANTITATIVE DATA: The pre- and post-scores from the YSR and SCS
      demonstrated no significant differences within the SP study participants or
      between the control group vs. the study group. FOCUS GROUP FINDINGS: The initial
      focus group acted as a debriefing exercise and prompted the adolescents to
      request that they come out of their role when giving feedback. Subsequent focus
      group discussion was around the medical student performance and their family
      doctors. CONCLUSION: Adolescent females showed no adverse effects when used
      extensively to portray risk-taking SPs. The focus groups provided the adolescents
      with an opportunity to debrief together. The adolescent SPs reported benefiting
      from this study but requested unanimously that they come "out of character" when
      giving feedback to the medical students.

PMID- 16441321
TI  - The effect of defined violations of test security on admissions outcomes using
      multiple mini-interviews.
AB  - INTRODUCTION: Heterogeneous results exist regarding the impact of security
      violations on student performances in objective structured clinical examinations
      (OSCEs). Three separate studies investigate whether anticipated security
      violations result in undesirable enhancement of MMI performance ratings. METHODS:
      Study 1: low-stakes: MMI station stems provided to a random half of 57 medical
      school applicants 2 weeks in advance of participation in a research study. Study
      2: high-stakes: 384 medical school applicants sat a 12-station MMI to determine
      admission. Each half received 1 of 2 pilot MMI station stems 2 weeks in advance.
      Study 3: high-stakes: 38 interviewees with dual applications to occupational
      therapy and physiotherapy experienced the same 7-station MMI twice on the same
      date. RESULTS: No statistically significant differences in MMI performances were
      detected. CONCLUSIONS: Predictable violations of MMI security do not unduly
      influence applicant performance ratings.

PMID- 16441322
TI  - Professionalism in general practice: development of an instrument to assess
      professional behaviour in general practitioner trainees.
AB  - INTRODUCTION: The aim of this study is to develop a new tool to assess
      professional behaviour in general practitioner (GP) trainees: the evaluation of
      professional behaviour in general practice (EPRO-GP) instrument. METHODS: Our
      study consisted of 4 phases: (1) development of a model of professionalism in
      general practice based on a literature review on professionalism, competency
      models of general practice and the overall educational objectives of postgraduate
      training for general practice; (2) development of the EPRO-GP instrument in
      collaboration with a sounding board; (3) establishing the content validity of the
      EPRO-GP instrument using a nominal group technique; and (4) establishing the
      feasibility of the EPRO-GP instrument in 12 general practice trainees and their
      general practice trainers. RESULTS: The model of professionalism in general
      practice encompassed 4 themes within professionalism: (a) professionalism towards
      the patient; (b) professionalism towards other professionals; (c) professionalism
      towards the public; and (d) professionalism towards oneself. These 4 themes
      covered 26 elements of professionalism. This model provided the framework of the
      EPRO-GP instrument, which we developed further by operationalising the 26
      elements in 127 behavioural items. The expert ratings confirmed the content
      validity of the instrument with one exception: the element "altruism" was removed
      as a stand-alone category but it remained throughout the tool in items giving
      primacy to patient welfare. The results on the feasibility of the EPRO-GP
      instrument were very encouraging. All tutorials yielded professional behaviour
      learning points. DISCUSSION: Our results support the content validity of the EPRO
      GP instrument as well as its feasibility as a tool to educate for professionalism
      in general practice.

PMID- 16441323
TI  - In-training assessment: qualitative study of effects on supervision and feedback
      in an undergraduate clinical rotation.
AB  - BACKGROUND: Supervision and feedback are essential factors that contribute to the
      learning environment in the context of workplace learning and their frequency and
      quality can be improved. Assessment is a powerful tool with which to influence
      students' learning and supervisors' teaching and thus the learning environment.
      OBJECTIVE: To investigate an in-training assessment (ITA) programme in action and
      to explore its effects on supervision and feedback. DESIGN: A qualitative study
      using individual, semistructured interviews. SUBJECTS AND SETTING: Eight students
      and 17 assessors (9 members of staff and 8 residents) in the internal medicine
      undergraduate clerkship at Vrije Universiteit Medical Centre, Amsterdam, the
      Netherlands. RESULTS: The ITA programme in action differed from the intended
      programme. Assessors provided hardly any follow-up on supervision and feedback
      given during assessments. Although students wanted more supervision and feedback,
      they rarely asked for it. Students and assessors failed to integrate the whole
      range of competencies included in the ITA programme into their respective
      learning and supervision and feedback. When giving feedback, assessors rarely
      gave borderline or fail judgements. DISCUSSION AND CONCLUSION: If an ITA
      programme in action is to be congruent with the intended programme, the
      implementation of the programme must be monitored. It is also necessary to
      provide full information about the programme and to ensure this information is
      given repeatedly. Introducing an ITA programme that includes the assessment of
      several competencies does not automatically lead to more attention being paid to
      these competencies in terms of supervision and feedback. Measures that facilitate
      change in the learning environment seem to be a prerequisite for enabling the
      assessment programme to steer the learning environment.

PMID- 16441324
TI  - Randomised, controlled study investigating the optimal instructor: student ratios
      for teaching suturing skills.
AB  - INTRODUCTION: Recently, there has been a shift away from practising procedures on
      patients for the first time and towards bench model teaching of clinical skills
      to undergraduate medical students. However, guidelines for the most effective
      instructor : student ratio for technical skills training are unclear. This has
      important implications for staffing laboratory based teaching sessions. The
      purpose of this study was to assess the optimal ratio of teachers to learners
      during the teaching of a simulated wound closure. METHODS: A total of 108
      undergraduate medical students participated in a 1-hour course on wound closure.
      They were randomised to 3 groups, each with a different instructor:student ratio
      (Group A: 6-12; Group B: 3-12; Group C: 1-12). Students were evaluated on a pre
      test, an immediate post-test and a delayed retention test using an objective,
      computer-based technical skills assessment method. Collectively termed the
      "economy of movements", the total time taken to complete the task and the number
      of movements executed were the primary outcome measures. RESULTS: Improvements in
      the economy of movements were the same for Groups A and B and were better than in
      Group C (P < 0.005). DISCUSSION: The optimal instructor:student ratio was 1
      instructor for 4 students. Higher ratios of instructors to students resulted in
      no improvements in learning, and lower ratios of instructors to students resulted
      in significantly less learning. These findings are in keeping with current motor
      learning theories.

PMID- 16441325
TI  - On the relationship between group functioning and study success in problem-based
      learning.
AB  - INTRODUCTION: In problem-based learning (PBL), discussion in the tutorial group
      plays a central role in stimulating student learning. Problems are the principal
      input for stimulating discussion. The quality of discussion is assumed to
      influence student learning and, in the end, study success. AIMS: To investigate
      the relationships between aspects of group functioning and study success.
      METHODS: First-year medical students (n = 116), forming 12 PBL groups, completed
      a 21-item questionnaire on various aspects of a PBL session. At the end of the
      unit, a course examination was administered. Scales were constructed and
      reliability analyses conducted. RESULTS: Group functioning and case quality were
      strongly correlated with students' grades in a course examination. Further,
      students' perceptions of group functioning, case quality and the quality of their
      own contribution were linked strongly with each other. CONCLUSIONS: Group
      functioning, case quality and study success are associated with each other in
      PBL. The interaction between these aspects of PBL in promoting learning calls for
      further investigation.

PMID- 16441326
TI  - To be and to have a critical friend in medical teaching.
AB  - BACKGROUND: In order to stimulate reflection and continuous professional
      development, a model of critical friends evaluating each other was introduced in
      medical education. OBJECTIVE: To investigate whether the critical friend concept
      can serve as a pragmatic model for evaluation of medical teachers and as a
      fruitful tool for enhancing self-knowledge and professional development among
      medical educators. METHODS: Three pairs of critical friends were formed,
      consisting of experienced medical teachers (n = 6) at the Karolinska Institutet.
      Each teacher was assigned to give 1 lecture and 1 seminar in his or her specific
      research or clinical field. The critical friend evaluated the performance in
      class, acting as an observer using a pre-formed protocol. The evaluation was
      communicated to the teacher during a 45-minute session within 48 hours after the
      teaching session. Each of the 6 teachers was criticised and gave criticism within
      the pair configurance. The outcome of the process was evaluated by an
      experimenter, not participating in the process, who performed a semistructured
      interview with each of the 6 teachers. RESULTS: Each teacher had a different way
      of reflecting on teaching after the project than before and made changes in his
      or her way of teaching. We also noted that being a critical friend may be even
      more effective than having one. The majority of the feedback provided was
      positive and valuable. CONCLUSION: To be and to have a critical friend is worth
      the extra workload. Therefore, the critical friend concept should be made part of
      regular teaching practice.

PMID- 16441327
TI  - A comparison study of career satisfaction and emotional states between primary
      care and speciality residents.
AB  - OBJECTIVE: To evaluate career satisfaction, emotional states and positive and
      negative experiences among residents in primary care and speciality programmes in
      1 academic medical centre prior to the implementation of the Accreditation
      Council for Graduate Medical Education's (ACGME) duty hour requirements. DESIGN:
      Cross-sectional survey. MEASUREMENTS: All 581 residents in the academic health
      centre were asked to participate voluntarily in a confidential survey; 327(56%)
      completed the survey. RESULTS: Compared to their primary care colleagues,
      speciality residents had higher levels of satisfaction with career choice,
      feelings of competence and excitement, lower levels of inferiority and fatigue
      and different perceptions of positive and negative training experiences. However,
      77% of all respondents were consistently or generally pleased with their career
      choices. The most positive residents' experiences related to interpersonal
      relationships and their educational value; the most negative experiences related
      to interpersonal relationships and issues perceived to be outside of residents'
      control. Age and training level, but not gender also influenced career
      satisfaction, emotional states and positive and negative opinions about
      residency. CONCLUSIONS: Less satisfaction with career choice and more negative
      emotional states for primary care residents compared to speciality residents
      probably relate to the training experience and may influence medical students'
      selections of careers. The primary care residents, compared to speciality
      residents, appear to have difficulty in fulfilling their ideals of
      professionalism in an environment where they have no control. These data provide
      baseline information with which to compare these same factors after the
      implementation of the ACGME duty hours' and competency requirements.

PMID- 16441328
TI  - Paired seminar-teaching by basic medical scientists and clinicians.

PMID- 16441330
TI  - Family decision-making for nursing home residents with dementia: rural-urban
      differences.
AB  - CONTEXT: Research has demonstrated substantial differences between end-of-life
      care in rural and urban settings. As the end of life approaches, rural elders are
      less likely to be hospitalized, to be placed in an intensive care unit, or to
      have a feeding tube, compared to their urban counterparts. These differences
      cannot be fully explained by rural-urban differences in access to medical
      services. PURPOSE: To describe and understand rural-urban differences in
      attitudes toward death and in end-of-life decision making. METHODS: Eight focus
      groups were convened in rural and urban Minnesota nursing homes. The 38 focus
      group participants were family members of nursing home residents with severe
      cognitive impairment. FINDINGS: Most rural focus group participants voiced
      unqualified acceptance of death and placed few conditions on death, beyond their
      hope that it would be quick and peaceful. Urban respondents presented a wider
      range of attitudes toward death, from unambiguous acceptance of immediate death
      to evident discomfort with welcoming death under any circumstances. These rural
      urban differences had practical implications. Rural respondents were much less
      likely to endorse interventions that would impede death, compared to their urban
      counterparts. CONCLUSIONS: Rural respondents tended to express confidence in
      natural forces; death was seen as neutral or beneficent. Resistance to the
      approach of death was more characteristic of urban respondents, some of whom
      insisted upon aggressive medical care in advanced dementia.

PMID- 16441331
TI  - Physical and mental health and access to care among nonmetropolitan Veterans
      Health Administration patients younger than 65 years.
AB  - CONTEXT: The 4.5 million military veterans treated by the Veterans Health
      Administration (VA) are believed to experience poorer physical and mental health
      than nonveterans. Furthermore, nonmetropolitan residents have less access to
      medical services, whether or not they are veterans in VA care. A direct
      comparison of metropolitan and nonmetropolitan veterans and nonveterans on a
      national health survey has not been reported, so it is not known whether
      nonmetropolitan VA patients experience similar medical need or access as other
      nonmetropolitan residents. PURPOSE: We sought to compare the perceptions of
      health status and access to care among metropolitan and nonmetropolitan veterans
      in VA care, other veterans, and nonveterans in a large national sample surveyed
      under the same conditions. METHODS: Male respondents to the 2000 Behavioral Risk
      Factor Surveillance System health survey were divided into veterans or
      nonveterans, VA users or nonusers, metropolitan or nonmetropolitan residents, and
      1 of 3 age groups (18-44, 45-64, and 65(+)). Responses to questions about current
      health status, health coverage, and access to care were submitted to chi-square
      analyses or analyses of variance, using SUDAAN software to compute survey error
      variance. FINDINGS: Nonmetropolitan VA patients younger than 65 years
      consistently reported the worst physical and mental health status and reduced
      access to care. CONCLUSIONS: VA can anticipate increasing demand for mental and
      physical health care among rural veterans younger than 65 years.

PMID- 16441332
TI  - Review of pesticide education materials for health care providers providing care
      to agricultural workers.
AB  - CONTEXT: Pesticide exposure is an important environmental and occupational health
      risk for agricultural workers and their families, but health care providers
      receive little training in it. OBJECTIVE: To evaluate the medical resources
      available to providers caring for patients, particularly farmworkers, exposed to
      pesticides and to recommend a selective bibliography for use in educating
      clinicians about pesticides and health care. These resources are divided into 3
      domains: (1) the working knowledge, (2) the skill set, and (3) the references
      needed to care for these patients. METHODS: We searched library databases dating
      back to 1995, as well as conference materials and Internet resources. Materials
      were included only if they were readily available through customary sources.
      Materials were randomly divided into 2 groups. Two authors wrote detailed reviews
      for each group. The remaining authors read each document and review, making
      changes that were agreed upon by the team. Review procedures were standardized to
      examine the contemporary relevance, quality, and overall strengths and weaknesses
      of the material relative to guidelines developed for each domain. These
      guidelines were developed from the authors' experience, national focus groups,
      and literature review. RESULTS: While no 1 resource adequately addresses all
      needs, a number of resources were identified addressing the categories of working
      knowledge, skill set, and reference materials. Few of the reviewed materials
      address the cultural competence of providers treating farmworkers. Additional
      education resources are needed.

PMID- 16441333
TI  - Social and emotional impacts of farmwork injuries: an exploratory study.
AB  - CONTEXT: The physical hazards of farming have been extensively studied and
      reported upon. Far less studied are the social and emotional impacts of farmwork
      injuries and deaths. PURPOSE: To investigate and document broad but targeted
      issues regarding the impact on individuals, families, and communities of farmwork
      injuries and fatalities of farmer leaders. METHODS: Ten incidents of farmwork
      injuries with disabilities or fatalities in Pennsylvania were used for a
      collective case study. Data were collected through a total of 47 interview
      sessions with 66 individuals including next of kin, other family members, injured
      persons, and community members. Thematic analysis was used to identify themes and
      issues in this descriptive study. FINDINGS: Community members missed the rich,
      broad, and comprehensive skills, abilities, and perspectives that farmers brought
      to community service. Participants expressed that the community assistance and
      support provided to injured persons and families benefited not only the injured
      persons and their families and farms but also the community members. Participants
      reported emotional anguish and loss as well as positive transformations and
      consequences. As expressed by participants, God and religion play an important
      role in their beliefs regarding the occurrence and outcome of farmwork injury
      incidents. CONCLUSIONS: Social and emotional impacts on individuals, families,
      and communities are varied and multileveled. The role that religion and
      storytelling play in the process of dealing with serious injury incidents raises
      questions regarding agricultural injury prevention.

PMID- 16441334
TI  - The effect of rural residence on dental unmet need for children with special
      health care needs.
AB  - BACKGROUND: Unmet need for dental care is the most prevalent unmet health care
      need among children with special health care needs (CSHCN), even though these
      children are at a greater risk for dental problems. The combination of rural
      residence and special health care needs may leave rural CSHCN particularly
      vulnerable to high levels of unmet dental needs. OBJECTIVE: To examine the
      effects of rural residence on unmet dental need for CSHCN. METHODS: We use the
      nationally representative National Survey of CSHCN Needs. We performed logistic
      regression to estimate the independent effects of rural residence on the
      likelihood of having an unmet dental need, using a measure of unmet need based on
      professional society recommendations and a measure based on parental report.
      RESULTS: Using either of the measures, a substantial percentage of CSHCN do not
      receive all needed dental care. Rural CSHCN are more likely to forgo needed
      dental care than their urban counterparts. Our results suggest that rural CSHCN
      have unmet needs for dental care due to both difficulty accessing care and
      because their parents do not recognize a need. CONCLUSION: Traditional access
      barriers for rural children, such as inadequate provider supply and lack of
      insurance, may increase unmet needs both directly and indirectly, through their
      effects on parents' perceptions of need. Reducing unmet needs for dental care in
      rural children with special needs will require addressing both access issues and
      parents' understanding of dental care need.

PMID- 16441335
TI  - Care across the continuum: access to health care services in rural America.

PMID- 16441336
TI  - Modeling the mental health workforce in Washington State: using state licensing
      data to examine provider supply in rural and urban areas.
AB  - CONTEXT: Ensuring an adequate mental health provider supply in rural and urban
      areas requires accessible methods of identifying provider types, practice
      locations, and practice productivity. PURPOSE: To identify mental health shortage
      areas using existing licensing and survey data. METHODS: The 1998-1999 Washington
      State Department of Health files on credentialed health professionals linked with
      results of a licensure renewal survey, 1990 US Census data, and the results of
      the 1990-1992 National Comorbidity Survey were used to calculate supply and
      requirements for mental health services in 2 types of geographic units in
      Washington state-61 rural and urban core health service areas and 13 larger
      mental health regions. Both the number of 9 types of mental health professionals
      and their full-time equivalents (FTEs) per 100,000 population measured supply in
      the health service areas and mental health regions. FINDINGS: Notable shortages
      of mental health providers existed throughout the state, especially in rural
      areas. Urban areas had 3 times the psychiatrist FTEs per 100,000 and more than
      1.5 times the nonpsychiatrist mental health provider FTEs per 100,000 as rural
      areas. More than 80% of rural health service areas had at least 10% fewer
      psychiatrist FTEs and nonpsychiatrist mental health provider FTEs than the state
      ratio (10.4 FTEs per 100,000 and 306.5 FTEs per 100,000, respectively). Ten of
      the 13 mental health regions were more than 10% below the state ratio of
      psychiatrist FTEs per 100,000. CONCLUSIONS: States gathering a minimum database
      at licensure renewal can identify area-specific mental health care shortages for
      use in program planning.

PMID- 16441337
TI  - Rural Illinois hospital chief executive officers' perceptions of provider
      shortages and issues in rural recruitment and retention.
AB  - BACKGROUND: It is important to assess rural health professions workforce needs
      and identify variables in recruitment and retention of rural health
      professionals. PURPOSE: This study examined the perspectives of rural hospital
      chief executive officers (CEOs) regarding workforce needs and their views of
      factors in the recruitment and retention process. METHODS: A survey was mailed to
      CEOs of 28 Illinois rural hospitals, in towns ranging from 3,396 to 33,530 in
      population size. The survey addressed CEO perceptions of number of physicians
      needed by specialty, need for other health professionals, and variables important
      to recruitment and retention. FINDINGS: Twenty-two CEOs (79%) responded to the
      survey. Eighty-six percent indicated a physician shortage in the community, with
      64% reporting the need for family physicians. CEOs also indicated the need for
      physicians in obstetrics-gynecology, general and orthopedic surgery, general
      internal medicine, cardiology, and psychiatry. In terms of needs for other health
      professionals, most often mentioned were registered nurses (91%), pharmacists
      (64%), and nurses' aides (46%). Related to recruitment and retention, most often
      mentioned by the CEOs was community attractiveness in general, followed by
      practice and physician career opportunities. CONCLUSIONS: CEOs offer 1 important
      perspective on health professions needs, recruitment, and retention in rural
      communities. While expressing a range of opinions, rural hospital CEOs clearly
      indicate the need for more primary care physicians, call for an increased
      capacity in nursing, and point to community development as a key factor in
      recruitment and retention.

PMID- 16441338
TI  - Rural residence and Hispanic ethnicity: doubly disadvantaged for diabetes?
AB  - CONTEXT: Hispanics are at increased risk for diabetes, while rural residents have
      historically had decreased access to care. PURPOSE: To determine whether living
      in a rural area and being Hispanic confers special risks for diagnosis and
      control of diabetes. METHODS: We analyzed the Third National Health and Nutrition
      Examination Survey (1988-1994). Hispanics and non-Hispanic white adults were
      classified according to rural/urban residence to create 4 ethnicity-residence
      groups. Investigated outcomes were previously diagnosed and undiagnosed diabetes.
      Among those with diagnosed diabetes, we investigated control of glucose,
      hypertension, and lipids. FINDINGS: The prevalence of diagnosed diabetes was
      greatest for rural residents, especially for rural Hispanics (8.2%) versus that
      for urban whites (4.6%), rural whites (6.5%), or urban Hispanics (4.5%), (P <
      .01). However, urban Hispanics were most likely to have undiagnosed diabetes at
      3.7%, versus 2.3% of rural whites, 2.8% of urban whites, and 2.7% of rural
      Hispanics (P = .04). Among people with diagnosed diabetes, there was no
      difference in glycemic control between the 4 groups. Rural Hispanics with
      diagnosed diabetes had the greatest prevalence of elevated systolic blood
      pressure at 45%, compared to 37% of urban whites, 29% of rural whites, 28% of
      urban Hispanics (P = .01). In regression models controlling for potential
      confounders, there were no differences among urban and rural whites and Hispanics
      in the likelihood of undiagnosed diabetes or in glycemic control for those with
      diagnosed diabetes. CONCLUSIONS: Initiatives that target Hispanic health, and
      especially diabetes, should acknowledge rural/urban Hispanic health differences.

PMID- 16441339
TI  - Practice locations of graduates of family physician residency and nurse
      practitioner programs: considerations within the context of institutional culture
      and curricular innovation through Titles VII and VIII.
AB  - BACKGROUND: Studies have described the aggregate results of federal funding for
      health professions education at the national level, but analysis of the long-term
      impact of institutional participation in these programs has been limited.
      PURPOSE: To describe and assess federally supported curricular innovations at
      East Tennessee State University designed to promote family medicine and nurse
      practitioner graduate interest in rural and underserved populations. METHODS:
      Descriptive analysis of a survey to determine practice locations of nurse
      practitioner graduates (1992-2002) and graduates of 3 family medicine residencies
      (1978-2002). Graduates' (N = 656) practice locations were documented using
      specific federal designations relating to health professions shortages and
      rurality. RESULTS: Overall, 83% of family medicine residency and 80% of nurse
      practitioner graduates selected practice locations in areas with medically
      underserved or health professions shortage designations; 48% of family physicians
      and 38% of nurse practitioners were in rural areas. CONCLUSIONS: Graduates who
      study in an educational setting with a mission-driven commitment to rural and
      community health and who participate in curricular activities designed to
      increase their experience with rural and underserved populations choose, in high
      numbers, to care for these populations in their professional practice.

PMID- 16441340
TI  - Posttraumatic stress disorder in rural primary care: improving care for mental
      health following bioterrorism.
AB  - CONTEXT: Recent bioterrorism attacks have highlighted the critical need for
      health care organizations to prepare for future threats. Yet, relatively little
      attention has been paid to the mental health needs of rural communities in the
      wake of such events. A critical aspect of bioterrorism is emphasis on generating
      fear and uncertainty, thereby contributing to increased needs for mental health
      care, particularly for posttraumatic stress disorder, which has been estimated to
      occur in 28% of terrorism survivors. PURPOSE: Prior experience with natural
      disasters suggests that first responders typically focus on immediate medical
      trauma or injury, leaving rural communities to struggle with the burden of unmet
      mental health needs both in the immediate aftermath and over the longer term. The
      purpose of the present article is to draw attention to the greater need to
      educate rural primary care providers who will be the frontline providers of
      mental health services following bioterrorism, given the limited availability of
      tertiary mental health care in rural communities. METHODS: We reviewed the
      literature related to bioterrorism events and mental health with an emphasis on
      rural communities. FINDINGS AND CONCLUSIONS: Public health agencies should work
      with rural primary care providers and mental health professionals to develop
      educational interventions focused on posttraumatic stress disorder and other
      mental disorders, as well as algorithms for assessment, referral, and treatment
      of post-event psychological disorders and somatic complaints to ensure the
      availability, continuity, and delivery of quality mental health care for rural
      residents following bioterrorism and other public health emergencies.

PMID- 16441341
TI  - Demographic and psychosocial characteristics of smokers and nonsmokers in low
      socioeconomic status rural Appalachian 2-parent families in Southern West
      Virginia.
AB  - CONTEXT: Rural Appalachian women living in poverty have a high prevalence of
      prenatal smoking; yet, few studies have examined this issue. PURPOSE: To
      investigate the demographic and psychosocial characteristics of prenatal smokers
      and nonsmokers in low-socioeconomic status, rural Appalachian 2-parent families.
      METHODS: During an 18-month period, two thirds of eligible low-socioeconomic
      status prenatal patients were recruited for a longitudinal study from a community
      health clinic in a rural West Virginia county. Data for the present report are
      from 92 women with a husband/partner (37 smokers and 55 nonsmokers) who completed
      a prenatal interview in the last trimester of pregnancy. This interview included
      demographics, personality traits, self-esteem problems, social support, and
      marital/partner relationship. FINDINGS: Compared to nonsmokers, prenatal smokers
      were less likely to have completed high school, less extroverted, and also had
      lower self-esteem, less intimate support, and more negative marital relationship.
      CONCLUSIONS: High school graduation and variables related to positive personality
      and supportive relationships distinguished smokers from nonsmokers. The causal
      relationship between these variables and prenatal smoking requires more work in
      larger and varied populations, and this study provides some direction for ongoing
      longitudinal investigation.

PMID- 16441342
TI  - Acute stroke care at rural hospitals in Idaho: challenges in expediting stroke
      care.
AB  - CONTEXT: Thrombolytics are currently the most effective treatment for stroke.
      However, the National Institute for Neurological Disorders and Stroke criteria
      for initiation of thrombolytic therapy, most notably the 3-hour time limit from
      symptom onset, have proven challenging for many rural hospitals to achieve.
      PURPOSE: To provide a snapshot of stroke care at rural hospitals in Idaho and to
      investigate the experiences of these hospitals in expediting stroke care.
      METHODS: Using a standard questionnaire, a telephone survey of hospital staff at
      21 rural hospitals in Idaho was performed. The survey focused on acute stroke
      care practices and strategies to expedite stroke care. FINDINGS: The median
      number of stroke patients treated per year was 23.3. Patient delays were reported
      by 77.8% of hospitals, transport delays by 66.7%, in-hospital delays by 61.1%,
      equipment delays by 22.2%, and ancillary services delays by 61.1%. Approximately
      67% of hospitals had implemented a clinical pathway for stroke and 80.0% had
      provided staff with stroke-specific training. No hospitals surveyed had a
      designated stroke team, and only 33.3% reported engaging in quality improvement
      efforts to expedite stroke care. Thrombolytics (tPA) were available and indicated
      for stroke at 55.6% of the hospitals surveyed. CONCLUSIONS: Rural hospitals in
      Idaho face many difficult challenges as they endeavor to meet the 3-hour deadline
      for thrombolytic therapy, including limited resources and experience in acute
      stroke care, and many different types of prehospital and in-hospital delays.

PMID- 16441344
TI  - Oxylipin analysis methods.
AB  - Practical guidelines for monitoring and measuring compounds such as jasmonates,
      ketols, ketodi(tri)enes and hydroxy-fatty acids as well as detecting the presence
      of novel oxylipins are presented. Additionally, a protocol for the penetrant
      analysis of non-enzymatic lipid oxidation is described. Each of the methods,
      which employ gas chromatography/mass spectrometry, can be applied without
      specialist knowledge or recourse to the latest analytical instrumentation.
      Additional information on oxylipin quantification and novel protocols for
      preparing oxygen isotope-labelled internal standards are provided. Four
      developing areas of research are identified: (i) profiling of the unbound
      cellular pools of oxylipins; (ii) profiling of esterified oxylipins and/or
      monitoring of their release from parent lipids; (iii) monitoring of non-enzymatic
      lipid oxidation; (iv) analysis of unstable and reactive oxylipins. The methods
      and protocols presented herein are designed to give technical insights into the
      first three areas and to provide a platform from which to enter the fourth area.

PMID- 16441345
TI  - Measuring multiple fluxes through plant metabolic networks.
AB  - Fluxes through metabolic networks are crucial for cell function, and a knowledge
      of these fluxes is essential for understanding and manipulating metabolic
      phenotypes. Labeling provides the key to flux measurement, and in network flux
      analysis the measurement of multiple fluxes allows a flux map to be superimposed
      on the metabolic network. The principles and practice of two complementary
      methods, dynamic and steady-state labeling, are described, emphasizing best
      practice and illustrating their contribution to network flux analysis with
      examples taken from the plant and microbial literature. The principal analytical
      methods for the detection of stable isotopes are also described, as well as the
      procedures for obtaining flux maps from labeling data. A series of boxes
      summarizing the key concepts of network flux analysis is provided for
      convenience.

PMID- 16441346
TI  - Analysis of protein phosphorylation: methods and strategies for studying kinases
      and substrates.
AB  - Protein phosphorylation is a highly conserved mechanism for regulating protein
      function, being found in all prokaryotes and eukaryotes examined. Phosphorylation
      can alter protein activity or subcellular localization, target proteins for
      degradation and effect dynamic changes in protein complexes. In many cases,
      different kinases may be involved in each of these processes for a single
      protein, allowing a large degree of combinatorial regulation at the post
      translational level. Therefore, knowing which kinases are activated during a
      response and which proteins are substrates is integral to understanding the
      mechanistic regulation of a wide range of biological processes. In this paper, I
      will describe methods for monitoring kinase activity, investigating kinase
      substrate specificity, examining phosphorylation in planta and the determination
      of phosphorylation sites in a protein. In addition, strategic considerations for
      experimental design and variables will be discussed.

PMID- 16441347
TI  - Methods and concepts in quantifying resistance to drought, salt and freezing,
      abiotic stresses that affect plant water status.
AB  - The abiotic stresses of drought, salinity and freezing are linked by the fact
      that they all decrease the availability of water to plant cells. This decreased
      availability of water is quantified as a decrease in water potential. Plants
      resist low water potential and related stresses by modifying water uptake and
      loss to avoid low water potential, accumulating solutes and modifying the
      properties of cell walls to avoid the dehydration induced by low water potential
      and using protective proteins and mechanisms to tolerate reduced water content by
      preventing or repairing cell damage. Salt stress also alters plant ion
      homeostasis, and under many conditions this may be the predominant factor
      affecting plant performance. Our emphasis is on experiments that quantify
      resistance to realistic and reproducible low water potential (drought), salt and
      freezing stresses while being suitable for genetic studies where a large number
      of lines must be analyzed. Detailed protocols for the use of polyethylene glycol
      infused agar plates to impose low water potential stress, assay of salt tolerance
      based on root elongation, quantification of freezing tolerance and the use of
      electrolyte leakage experiments to quantify cellular damage induced by freezing
      and low water potential are also presented.

PMID- 16441348
TI  - Practical approaches to plant volatile analysis.
AB  - Plants emit volatile organic compounds (VOCs) that play important roles in their
      interaction with the environment and have a major impact on atmospheric
      chemistry. The development of static and dynamic techniques for headspace
      collection of volatiles in combination with gas chromatography-mass spectrometry
      analysis has significantly improved our understanding of the biosynthesis and
      ecology of plant VOCs. Advances in automated analysis of VOCs have allowed the
      monitoring of fast changes in VOC emissions and facilitated in vivo studies of
      VOC biosynthesis. This review presents an overview of methods for the analysis of
      plant VOCs, including their advantages and disadvantages, with a focus on the
      latest technical developments. It provides guidance on how to select appropriate
      instrumentation and protocols for biochemical, physiological and ecologically
      relevant applications. These include headspace analyses of plant VOCs emitted by
      the whole organism, organs or enzymes as well as advanced on-line analysis
      methods for simultaneous measurements of VOC emissions with other physiological
      parameters.

PMID- 16441349
TI  - A step by step guide to phylogeny reconstruction.
AB  - The aim of this paper is to enable those who have never reconstructed a phylogeny
      to do so from scratch. The paper does not attempt to be a comprehensive
      theoretical guide, but describes one rigorous way of obtaining phylogenetic
      trees. Those who follow the methods outlined should be able to understand the
      basic ideas behind the steps taken, the meaning of the phylogenetic trees
      obtained and the scope of questions that can be answered with phylogenetic
      methods. The protocols have been successfully tested by volunteers with no
      phylogenetic experience.

PMID- 16441350
TI  - Imaging the live plant cell.
AB  - Observing a biological event as it unfolds in the living cell provides unique
      insight into the nature of the phenomenon under study. Capturing live cell data
      differs from imaging fixed preparations because living plants respond to the
      intense light used in the imaging process. In addition, live plant cells are
      inherently thick specimens containing colored and fluorescent molecules often
      removed when the plant is fixed and sectioned. For fixed cells, the
      straightforward goal is to maximize contrast and resolution. For live cell
      imaging, maximizing contrast and resolution will probably damage the specimen or
      rapidly bleach the probe. Therefore, the goals are different. Live cell imaging
      seeks a balance between image quality and the information content that comes with
      increasing contrast and resolution. That "lousy" live cell image may contain all
      the information needed to answer the question being posed--provided the
      investigator properly framed the question and imaged the cells appropriately.
      Successful data collection from live cells requires developing a specimen
      mounting protocol, careful selection and alignment of microscope components, and
      a clear understanding of how the microscope system generates contrast and
      resolution. This paper discusses general aspects of modern live cell imaging and
      the special considerations for imaging live plant specimens.

PMID- 16441351
TI  - Using intrinsically fluorescent proteins for plant cell imaging.
AB  - The intrinsically fluorescent proteins (IFPs), such as the green, cyan and yellow
      fluorescent proteins, have revolutionized how we can image the dynamics of
      cellular events. Intrinsically fluorescent proteins have been used as reporter
      genes to monitor transcriptional regulation, as targeted markers for organelles
      and subcellular structures, in fusion proteins to directly observe protein
      motility and dynamics, and in sensors designed to show changes in cellular
      environments ranging from pH to protein kinase activity. The IFPs hold tremendous
      potential to reveal the dynamic processes that underlie plant cell function;
      however, as with all technology there are artifacts and pitfalls inherent in
      their use. In this review, we highlight some of the practical issues in using
      IFPs for live cell imaging. These include choice of the appropriate IFP, dealing
      with autofluorescence, photobleaching and phototoxicity, and application of
      approaches such as fluorescence resonance energy transfer (FRET), fluorescence
      lifetime imaging (FLIM) and fluorescence recovery after photobleaching (FRAP) to
      gain high-resolution data about protein dynamics within the cell. We also discuss
      some of the more common artifacts associated with these fluorescence imaging
      approaches and suggest controls that should help both spot these problems and
      suggest their solutions.

PMID- 16441353
TI  - Microarray analysis of the transcriptome as a stepping stone towards
      understanding biological systems: practical considerations and perspectives.
AB  - DNA microarrays have been used to characterize plant transcriptomes to answer
      various biological questions. While many studies have provided significant
      insights, there has been great debate about the general reliability of the
      technology and data analysis. When compared to well-established transcript
      analysis technologies, such as RNA blot analysis or quantitative reverse
      transcription-PCR, discrepancies have frequently been observed. The reasons for
      these discrepancies often relate to the technical and experimental systems. This
      review-tutorial addresses common problems in microarray analysis and describes:
      (i) methods to maximize extraction of valuable biological information from the
      vast amount of microarray data and (ii) approaches to balance resource
      availability with high scientific standards and technological innovation with
      peer acceptability.

PMID- 16441352
TI  - Gateway-compatible vectors for plant functional genomics and proteomics.
AB  - Gateway cloning technology facilitates high-throughput cloning of target
      sequences by making use of the bacteriophage lambda site-specific recombination
      system. Target sequences are first captured in a commercially available "entry
      vector" and are then recombined into various "destination vectors" for expression
      in different experimental organisms. Gateway technology has been embraced by a
      number of plant laboratories that have engineered destination vectors for
      promoter specificity analyses, protein localization studies, protein/protein
      interaction studies, constitutive or inducible protein expression studies, gene
      knockdown by RNA interference, or affinity purification experiments. We review
      the various types of Gateway destination vectors that are currently available to
      the plant research community and provide links and references to enable
      additional information to be obtained concerning these vectors. We also describe
      a set of "pEarleyGate" plasmid vectors for Agrobacterium-mediated plant
      transformation that translationally fuse FLAG, HA, cMyc, AcV5 or tandem affinity
      purification epitope tags onto target proteins, with or without an adjacent
      fluorescent protein. The oligopeptide epitope tags allow the affinity
      purification, immunolocalization or immunoprecipitation of recombinant proteins
      expressed in vivo. We demonstrate the utility of pEarleyGate destination vectors
      for the expression of epitope-tagged proteins that can be affinity captured or
      localized by immunofluorescence microscopy. Antibodies detecting the FLAG, HA,
      cMyc and AcV5 tags show relatively little cross-reaction with endogenous proteins
      in a variety of monocotyledonous and dicotyledonous plants, suggesting broad
      utility for the tags and vectors.

PMID- 16441354
TI  - Transactivated and chemically inducible gene expression in plants.
AB  - Several vector systems are available for tissue-specific transactivation or
      chemical induction of transgene expression in plants. The choice facing
      researchers is which promoter system to commit to as this determines the range
      and characteristics of the expression resources available. The decision will not
      be the same for all species or applications. We present some general discussion
      on the use of these technologies and review in detail the properties in various
      (mainly angiosperm) species of the most promising: mGal4:VP16/UAS and pOp/LhG4
      for transactivation, and the alc-switch, GVE/VGE, GVG, pOp6/LhGR, and XVE systems
      for chemical induction.

PMID- 16441355
TI  - TILLING: practical single-nucleotide mutation discovery.
AB  - In the post-genomic sequencing era, an expanding portfolio of genomic
      technologies has been applied to the study of gene function. Reverse genetics
      approaches that provide targeted inactivation of genes identified by sequence
      analysis include TILLING (for Targeting Local Lesions IN Genomes). TILLING
      searches the genomes of mutagenized organisms for mutations in a chosen gene,
      typically single base-pair substitutions. This review covers practical aspects of
      the technology, ranging from building the mutagenized population to mutation
      discovery, and discusses possible improvements to current protocols and the
      impact of new genomic methods for mutation discovery in relation to the future of
      the TILLING approach.

PMID- 16441356
TI  - Transplantation across previously incompatible immunological barriers.
AB  - This article reviews recent advances, which allow the transplantation across or
      around previously incompatible immunological barriers such as a positive
      crossmatch or ABO blood group incompatibility.

PMID- 16441357
TI  - Lack of association between the -403G/A promoter polymorphism in the human
      CCL5/RANTES chemokine gene in liver transplant outcome.
AB  - Chemokines play a major role in the inflammatory and immune responses that
      mediate allograft outcome. CCL5/RANTES expansion chemokine is potent eosinophil,
      monocyte, basophils and lymphocyte chemoattractant and has recently been studied
      in transplantation with discrepant results, but systemic concentrations have been
      correlated to liver graft survival and incidence of rejection. Recent studies
      revealed that a functional mutation at -403 in the promoter may have a
      significance for inflammatory and infectious immune responses. Our objective was
      to investigate CCL5/RANTES promoter polymorphism in rejection and graft survival
      in liver transplant. We examined the CCL5/RANTES polymorphism in a series of 218
      liver transplants and 101 healthy Caucasian subjects. CCL5/RANTES genotyping was
      performed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). After comparing recipients (with acute rejection episodes versus
      without rejection) with the control population, we found no significant deviation
      in the distribution of the alleles or genotypes of CCL5/RANTES dimorphism in any
      comparison (P > 0.05). Indeed, 5 years allograft survival was 61.3% in recipients
      with the GG genotype against 58.8% in recipients with the GA and AA genotypes.
      These differences were also not statistically significant. In conclusion, human
      CCL5/RANTES gene promoter polymorphism does not seem to influence acute rejection
      development and allograft survival in liver recipients.

PMID- 16441358
TI  - The repercussions of implementing flow cytometry as a single HLA antibody
      screening technique in prospective renal transplant recipients.
AB  - In an effort to replace the complement-dependent cytotoxicity test (CDC) with a
      more sensitive single technique we looked at flow cytometry as a possible
      replacement. The Flow PRA Bead technique (One Lambda) performed well in our
      laboratory. Although as expected this technique was more sensitive and specific
      than CDC, there remained 11 samples from eight patients which were flow negative,
      CDC positive. The results of various antibody identification tests on these
      samples prompted us to alter the positive selection criteria which we had been
      using on our routine screening with the Flow PRA Beads and persuaded us that the
      initial CDC result was correctly positive in nine of the 11 samples.

PMID- 16441360
TI  - Triangular and self-triangulating cavocavostomy for orthotopic liver
      transplantation without posterior suture lines: a modified surgical technique.
AB  - A modified caval preservation technique with the potential for decreased
      incidence of venous outflow obstruction and haemorrhage.

PMID- 16441359
TI  - An aggressive systematic strategy for acute respiratory distress syndrome caused
      by severe pneumonia after renal transplantation.
AB  - Acute respiratory distress syndrome (ARDS) caused by pneumonia after renal
      transplantation was usually associated with overimmunosuppression and high
      mortality rate. We evaluated the efficacy of an aggressive systemic protocol
      including strategies improving body's immune function. Twenty-one recipients were
      enrolled in this study. Patients were subjected to a protocol including (i)
      withdrawal of most immunosuppressants, (ii) early use of immunoenhancers and
      continuous renal replacement therapy (CRRT), (iii) reasonable administration of
      antibiotic regimen, (iv) prompt mechanical ventilating strategy, and (v) adequate
      nutrition. Immunosuppressants were adjusted according to the value of CD4+, CD8+T
      lymphocytes in peripheral blood. CRRT was conducted at once when patients were
      admitted to the intensive care unit (ICU), regardless the graft function.
      Thirteen (62%) survived and eight died finally. This is a high survival rate for
      this kind of patients. Eighteen patients had received thymosin treatment. All
      patients who survived experienced renal allograft dysfunction during CRRT, but
      when CRRT stopped, the function of all grafts gradually recovered. No acute
      rejection episodes were documented during the treatment. The aggressive systemic
      protocol including strategies improving the body's immune function and CRRT can
      improve the outcome of patients with ARDS after renal transplantation. The count
      of CD4+, CD8+T lymphocytes of peripheral blood is useful in the adjustment of
      immunosuppressants and the prediction of patient outcome.

PMID- 16441361
TI  - Impact of biliary complications in right lobe living donor liver transplantation.
AB  - Biliary reconstruction is one of the most challenging parts of right lobe living
      donor liver transplantation (RL LDLT), and biliary complications have been
      reported as the first source of surgical complications of this procedure. We
      reviewed biliary reconstruction and complications in 27 consecutive RL LDLTs. We
      compared the first 14 procedures (group 1) to the last 13 (group 2). Seven
      patients (25.9%) experienced a biliary complication (five leaks and two
      strictures). The incidence of biliary complications was 11.1% in RL grafts with a
      single duct and 55.5% in graft presenting multiple bile ducts (P = 0.03). Four of
      the 18 patients with a duct-to-duct reconstruction (22.2%) and three of the 11
      patients with a Roux-en-Y reconstruction (27.3%) developed a biliary complication
      (P = ns). The incidence of biliary complications significantly decreased from
      42.9% (n = 6) in the first group to 7.6% (n = 1) in the second group (P = 0.05).
      The overall 1-year graft and patient survival were 57.1% and 64.3% in group 1
      versus 100.0% and 100% in group 2 (P = 0.01; P = 0.006). Biliary complications
      remain one of the most important technical complications affecting RL LDLT.
      Nevertheless, attention and surgical refinement can lead to a significant
      reduction of the biliary complication rate, improving graft and patient survival.

PMID- 16441362
TI  - Characterization of rejection episodes in patients following positive crossmatch
      and ABO-incompatible live donor renal transplantation.
AB  - For kidney transplant recipients with donor-specific antibody (DSA) to HLA- (+XM)
      or ABO-antigens (ABOI), there is a need to improve detection and treatment of
      antibody-mediated rejection (AMR). The methods included a retrospective review of
      consecutive patients that received plasmapheresis and immune globulin (PPIVIg) to
      abrogate +XM or ABOI. Twelve patients were transplanted after PPIVIg (+XM = 9,
      ABOI = 2, +XM/ABOI = 1). No hyperacute rejections occurred. Rejection occurred in
      seven patients [four AMR, three acute cellular rejection (ACR)]. In four +XM
      patients, DSA was detected during graft dysfunction despite lack of histologic
      and C4d features of AMR. In one patient, DSA preceded the histologic and
      immunofluorescent features of AMR. In another patient with borderline changes and
      DSA, graft function improved after PPIVIg, despite lack of histologic or
      immunofluorescent evidence of AMR. One patient with Banff IIA ACR and DSA treated
      with antithymocyte antibody but not PPIVIg had recurrent rejections and poor
      graft function. In +XM and ABOI recipients with graft dysfunction: (i) DSA may
      represent AMR in the absence of C4d or histologic features of AMR; (ii) DSA can
      precede C4d or light microscopic features of AMR; (iii) A poor outcome may result
      if DSA or continued allograft dysfunction is present and not treated despite a
      negative biopsy.

PMID- 16441363
TI  - Renal calcium handling after rapamycin conversion in chronic allograft
      dysfunction.
AB  - To study the effect of rapamycin on calcium balance, we conducted a prospective
      study on transplant recipients. The patients were converted to rapamycin and
      observed for 6 months (C). Urinary Ca and P, ALK-p, Ca, P, and intact parathyroid
      hormone (iPTH) were examined before and 6 months after conversion. A
      nonconversion group (N) was found for comparison. Sixteen patients entered the
      study. There were increases of ALK-p (C: 67.4 +/- 32.9 to 79.6 +/- 37.0*; N: 67.3
      +/- 25.1 to 67.8 +/- 14.7 IU) (*P < 0.05), Ca(2+) (C: 8.7 +/- 0.3 to 9.5 +/-
      0.2*; N: 8.8 +/- 0.4 to 8.7 +/- 0.5 mg/dl), urinary P excretion (C: 287.6 +/-
      257.1 to 439.4 +/- 260.9*; N: 233.9 +/- 117.2 to 264.8 +/- 143.4 mg/day) and iPTH
      (C: 133.7 +/- 149.6 to 200.6 +/- 171.5*; N: 128.4 +/- 57.1 to 136.3 +/- 40.4
      pg/ml). Serum P (C: 5.3 +/- 1.4 to 3.6 +/- 0.6*; N: 5.2 +/- 0.8 to 5.1 +/- 0.9
      mg/dl) and urinary Ca(2+) (C: 93.9 +/- 52.6 to 31.8 +/- 45.1*; N: 84.6 +/- 38.3
      to 75.9 +/- 38.4 mg/day) were decrease. Rapamycin was associated with decreased
      urinary Ca(2+) and increased P excretion. The alteration might come from the
      increased parathyroid hormone.

PMID- 16441364
TI  - Molecular signature of mice T lymphocytes following tolerance induction by
      allogeneic BMT and CD40-CD40L costimulation blockade.
AB  - Tolerance induction by mixed chimerism and costimulation blockade is a promising
      approach to avoid immunosuppression, but the molecular basis of tolerant T
      lymphocytes remains elusive. We investigated the genome-wide gene expression
      profile of murine T lymphocytes after tolerance induction by allogeneic bone
      marrow transplantation (BMT) and costimulatory blockade using the anti-CD40L
      antibody MR1. Molecular functions, biological processes, cellular locations, and
      coregulation of identified genes were determined. A total of 113 unique genes
      exhibited a significant differential expression between the lymphocytes of MR1
      treated Tolerance (TOL) and untreated recipients Control (CTRL). The majority of
      genes upregulated in the TOL group are involved in several signal transduction
      cascades such as members of the MAPKKK cascade (IL6, Tob2, Stk39, and Dusp24).
      Other genes involved in lymphocyte differentiation and highly expressed in the
      TOL group are lymphotactin, the estrogen receptors (ERs) and the suppressor of
      cytokine signaling 7. Common transcription factors such as ER 1 alpha, GATA
      binding protein 1, insulin promoter factor 1, and paired-related homeobox 2 could
      be identified in the promoter regions of upregulated genes in the TOL group.
      These data suggest that T lymphoctes of tolerant mice exhibit a distinct
      molecular expression profile, which needs to be evaluated in other experimental
      tolerance models to determine whether it is a universal signature of tolerance.

PMID- 16441365
TI  - Incidence and cytotoxicity of antibodies in cynomolgus monkeys directed to nonGal
      antigens, and their relevance for experimental models.
AB  - The recent availability of pigs homozygous for alpha1,3-galactosyltransferase
      gene-knockout (GT-KO) has enabled the study of incidence and cytotoxicity of
      antibodies of cynomolgus monkeys directed to antigens other than Galalpha1,3Gal
      (Gal), termed nonGal antigens. To this aim, sera from 21 cynomolgus monkeys were
      tested by flow cytometry for binding of IgM and IgG to peripheral blood
      mononuclear cells (PBMC) from wild-type (WT) and GT-KO pigs. The sera were also
      tested for complement-dependent cytotoxicity to WT and GT-KO PBMC. Anti-WT IgM
      and IgG were found in 100% and 95%, respectively, and anti-GT-KO IgM and IgG in
      76% and 66%, respectively, in the sera of the monkeys tested (P < 0.01). Whereas
      100% of sera were cytotoxic to WT PBMC, only 76% were cytotoxic to GT-KO PBMC,
      and the level of cytotoxicity was significantly less (P < 0.01). Although the
      incidence and cytotoxicity of antibodies in monkey sera to GT-KO pig PBMC are
      significantly less than to WT PBMC, approximately three-quarters of the monkeys
      tested had cytotoxic antibodies to GT-KO PBMC. This incidence of cytotoxicity is
      significantly higher than that found in baboons and humans, suggesting the baboon
      may be an easier and possibly more suitable model to study antibody-mediated
      rejection of transplanted GT-KO pig organs and cells.

PMID- 16441366
TI  - Parvovirus B19-induced anemia in renal transplantation: a role for rHuEPO in
      resistance to classical treatment.
AB  - Human parvovirus B19 (PVB 19) is responsible for pure red cell aplasia in
      immunocompromised patients, and particularly solid organ recipients. Intravenous
      immunoglobulins (IVIG) have been shown to be efficient to achieve the correction
      of anemia in association with the reduction of immunosuppression. We report a
      case of kidney transplant recipient with PVB 19-induced anemia that did not
      respond to recombinant human erythropoietin (rHuEPO) and to a first course of
      IVIG. After discontinuation of rHuEPO, a second course of IVIG was successful
      with the resolution of anemia. We discuss the role of rHuEPO that may facilitate
      PVB 19 replication in erythropoietin-sensitive human erythroid progenitor cells.

PMID- 16441367
TI  - Pure red cell aplasia associated with concomitant use of mycophenolate mofetil
      and ribavirin in post-transplant recurrent hepatitis C.

PMID- 16441368
TI  - Fulminant liver failure due to Clostridium perfringens sepsis 9 years after liver
      transplantation.

PMID- 16441369
TI  - Numbers and transported state of Escherichia coli in runoff direct from fresh
      cowpats under simulated rainfall.
AB  - AIMS: To investigate the number of Escherichia coli in runoff derived directly
      from fresh cowpats and to determine if the E. coli are attached to dense
      particles, in flocs or as individual cells. METHODS AND RESULTS: Three cowpats
      were collected monthly from the same farm for 13 months and the number of E. coli
      in them estimated. A rainfall simulator was used to generate runoff from the
      individual cowpats, which was fractioned to determine the transported state of
      any E. coli present. The number of E. coli in the cowpat runoff was highly
      variable and was strongly correlated with the number of E. coli in the cowpat.
      Only a small percentage (approx. 8%) of the E. coli in runoff were attached to
      dense (>1.3 g ml(-1)) particles and there was no evidence of flocculation of the
      cells. CONCLUSIONS: Escherichia coli in runoff from cowpats are transported
      predominantly as individual cells. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Mitigation strategies to reduce the number of faecal bacteria in overland flow
      from agricultural land need to be designed to trap single bacterial cells.

PMID- 16441370
TI  - Interaction of live and dead Escherichia coli O157:H7 and fluorescent
      microspheres with lettuce tissue suggests bacterial processes do not mediate
      adherence.
AB  - AIMS: The goal of this study was to determine whether any specific bacterial
      processes (biochemical or genetic) or cell surface moieties were required for the
      interaction between Escherichia coli O157:H7 and lettuce plant tissue. METHODS
      AND RESULTS: Escherichia coli O157:H7 and Fluospheres (fluorescent polystyrene
      microspheres) were used in experiments to investigate interactions with lettuce.
      Fluospheres were used as they are a non-biological material, of similar size and
      shape to a bacterial cell, but lack bacterial cell surface moieties and the
      ability to respond genetically. Live and glutaraldehyde-killed E. coli O157:H7
      attached at levels of c. 5.8 log(10) cells per cm(2) following immersion of
      lettuce pieces into a suspension containing c. 8 log(10) CFU ml(-1). In a
      separate experiment, numbers of bacteria or Fluospheres associated with lettuce
      decreased by c. 1.5 log cm(-2) following a 1-min wash. Exposure times of 1 min, 1
      h, or 6 h had little effect on the level of attachment for Fluospheres, and live
      or killed cells of E. coli O157:H7 to lettuce tissue. SIGNIFICANCE: These results
      indicate that bacterial processes and cell surface moieties are not required for
      the initial interaction of E. coli O157:H7 to lettuce plant tissue.

PMID- 16441371
TI  - Mutagenic effect of acridine orange on the expression of penicillin G acylase and
      beta-lactamase in Escherichia coli.
AB  - AIMS: The present work aimed to improve the production of penicillin G acylase
      (PGA) and reduce the beta-lactamase activity through acridine orange (AO) induced
      mutation in Escherichia coli. METHODS AND RESULTS: Three wild E. coli strains
      BDCS-N-FMu10, BDCS-N-S21 and BDCS-N-W50, producing both the enzymes PGA and beta
      lactamase were treated by AO. Minimum inhibitory concentration of AO was 10
      microg ml(-1) and it was noted that bacterial growth was gradually suppressed by
      increasing the concentration of AO from 10 to 100 microg ml(-1). The highest
      concentration that gave permissible growth rate was 50 microg ml(-1). The
      isolated survivals were screened on the bases of PGA and beta-lactamase
      activities. Among the retained mutants, the occurrence of beta-lactamase
      deficient ones (91%) was significantly higher than penicillin acylase deficient
      ones (27%). CONCLUSIONS: In seven of the mutants, PGA activity was enhanced with
      considerable decrease in beta-lactamase activity. One of the mutant strains (BDCS
      N-M36) exhibited very negligible expression of beta-lactamase activity and
      twofold increase in PGA activity [12.7 mg 6-amino-penicillanic acid (6-APA) h(-1)
      mg(-1) wet cells] compared with that in the wild-type strain (6.3 mg 6-APA h(-1)
      mg(-1) wet cells). SIGNIFICANCE AND IMPACT OF THE STUDY: The treatment of E. coli
      cells with AO resulted in mutants with enhanced production of PGA and
      inactivation of beta-lactamase. These mutants could be used for industrial
      production of PGA.

PMID- 16441372
TI  - Isolation of E. coli O157:H7 and non-O157 STEC in different matrices: review of
      the most commonly used enrichment protocols.
AB  - AIMS: To review and characterize the enrichment protocols used for detecting all
      Shiga-Toxin producing Escherichia coli (STEC) from different matrices. METHODS
      AND RESULTS: Firstly, the frequency distribution of the factors characterizing
      the enrichment protocols is described; secondly, a multiple correspondence
      analysis is performed to display profiles of association of these factors, and
      thirdly, published results concerning the relative performances of the protocols
      are summarized. Trypticase Soy Broth (TSB) is reported as the most frequently
      used enrichment broth. More often, one antibiotic is added in enrichment broths
      and these broths are incubated for a duration of 16-24 h at 35-37 degrees C. It
      also appears that the incubation temperature does not seem to be related to the
      type of serogroup looked for and that antibiotics are used regardless of the
      matrix analysed. Finally, results relating to the enrichment protocol efficacy
      are rare and differ from one study to another. CONCLUSIONS: Statistical studies
      must be conducted so as to assess the efficacy of the main enrichment protocols
      investigated in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      reviews the most commonly used enrichment protocols and highlights the lack of
      results as to their relative efficacy.

PMID- 16441373
TI  - Vegetative insecticidal protein enhancing the toxicity of Bacillus thuringiensis
      subsp kurstaki against Spodoptera exigua.
AB  - AIMS: The objective of this work was to enhance the insecticidal activity or
      widen the pesticidal spectrum of a commercial Bacillus thuringiensis strain
      YBT1520. METHODS AND RESULTS: A vegetative insecticidal protein gene vip3Aa7,
      under the control of its native promoter and cry3A promoter, was subcloned into
      B. thuringiensis acrystalliferous BMB171 to generate BMB8901 and BMBvip
      respectively. It was found that the amount of Vip3Aa7 protein produced by BMBvip
      was 3.2-fold more than that produced by BMB8901. Therefore, the vip3Aa7 gene
      under the control of cry3A promoter was transformed into strain YBT1520. The
      toxicity of the resulting strain BMB218V against Spodoptera exigua was 10-fold
      more than that of YBT1520, and that the toxicity of BMB218V against Helicoverpa
      armigera retained the same level as that of strain YBT1520. CONCLUSIONS: Strain
      YBT1520 obtained high toxicity against S. exigua after it was transformed and
      expressed the foreign vip3Aa7 gene. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Commercial B. thuringiensis strain YBT1520 has high toxicity against H. armigera
      and Plutella xylostella, but almost no activity against S. exigua, which is a
      major crop pest in China. This work provides a new strategy for widening the
      activity spectrum of B. thuringiensis against agriculture pests.

PMID- 16441374
TI  - Evaluation of Colilert-18 for the detection of coliforms and Escherichia coli in
      tropical fresh water.
AB  - AIMS: To evaluate the suitability of Colilert-18 in detecting Escherichia coli
      and total coliforms in tropical freshwater samples. METHODS AND RESULTS: Target
      organisms were isolated from yellow-fluorescent and yellow wells of Colilert
      18/Quanti-Tray using m-TEC agar and m-ENDO LES agar respectively. All the
      selected isolates were first identified based on their fatty acid methyl ester
      profile. Isolates showing contradictory results to that of the Colilert-18
      procedure were re-identified using API 20E strips. A total of 357 isolates, 177
      from yellow-fluorescent wells and 180 from yellow wells, were identified.
      CONCLUSIONS: The false-positive and -negative rates for E. coli detection using
      Colilert-18 were 36.4% and 11%, respectively, while for coliform detection the
      false-positive rate was 10.3%. SIGNIFICANCE AND IMPACT OF THE STUDY: The high
      false-positive rate of Colilert-18, tempers its value for E. coli detection when
      used for tropical freshwater samples.

PMID- 16441375
TI  - Fast identification of ten clinically important micro-organisms using an
      electronic nose.
AB  - AIMS: To evaluate the electronic nose (EN) as method for the identification of
      ten clinically important micro-organisms. METHODS AND RESULTS: A commercial EN
      system with a series of ten metal oxide sensors was used to characterize the
      headspace of the cultured organisms. The measurement procedure was optimized to
      obtain reproducible results. Artificial neural networks (ANNs) and a k-nearest
      neighbour (k-NN) algorithm in combination with a feature selection technique were
      used as pattern recognition tools. Hundred percent correct identification can be
      achieved by EN technology, provided that sufficient attention is paid to data
      handling. CONCLUSIONS: Even for a set containing a number of closely related
      species in addition to four unrelated organisms, an EN is capable of 100% correct
      identification. SIGNIFICANCE AND IMPACT OF THE STUDY: The time between isolation
      and identification of the sample can be dramatically reduced to 17 h.

PMID- 16441376
TI  - Quantitative detection of Streptococcus mutans in the dental plaque of Japanese
      preschool children by real-time PCR.
AB  - AIMS: To detect quantitatively the total bacteria and Streptococcus mutans in
      dental plaque by real-time PCR with prbac, Sm and GTF-B primers, and to compare
      their presence with the prevalence of dental caries in Japanese preschool
      children. METHODS AND RESULTS: Human dental plaque samples were collected from
      the labial surfaces of the upper primary central incisors of 107 children. The
      dental status was recorded as dft by WHO caries diagnostic criteria. Positive dt
      and dft scores by the Sm or GTF-B primer were significantly higher than negative
      scores (P < 0.01). The proportions of Strep. mutans to the total bacteria from
      sound, and sound and/or filled upper primary incisors were significantly lower
      than those from decayed or filled, and decayed incisors, respectively (P < 0.01).
      CONCLUSIONS: The ratios of Strep. mutans to total bacteria in plaque detected by
      real-time PCR with Sm and GTF-B primers were closely associated with the
      prevalence of dental caries in Japanese preschool children. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These assays may be useful for the assessment of an
      individual's risk of dental caries.

PMID- 16441377
TI  - Disruption of ste23 gene affects composition profile and bioactivity of
      exopolysaccharide produced by Streptomyces sp. 139.
AB  - AIMS: To study the function of the gene ste23 involved in the biosynthesis of
      Ebosin. METHODS AND RESULTS: In search of databases, the deduced product of the
      gene ste23 showed high homology to dTDP-4-dehydrorhamnose 3,5-epimerases. ste23
      was replaced by a kanamycin resistance gene through double crossover. Compared
      with Ebosin, an exopolysaccharide (EPS) produced by wild-type Streptomyces sp.
      139, the EPS produced by the ste23 mutant (designated EPS1) had a remarkably
      different monosaccharide composition and significantly diminished rhamnose
      content, though the molecular mass of EPS1 was similar to that of Ebosin. In
      addition, EPS1 lost the interleukin 1 (IL-1) antagonist activity in vitro.
      CONCLUSIONS: ste23 may be involved in the Ebosin biosynthesis in S. sp. 139. and
      its bioactivity. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first genetic
      work investigating functions of genes involved in EPS production in streptomyces
      by gene replacement of the pathway genes.

PMID- 16441378
TI  - In vitro inhibitory effect of hen egg white lysozyme on Clostridium perfringens
      type A associated with broiler necrotic enteritis and its alpha-toxin production.
AB  - AIMS: Clostridium perfringens type A causes both clinical and subclinical forms
      of necrotic enteritis in domestic avian species. In this study the inhibitory
      effect of hen egg white lysozyme on the vegetative form of Cl. perfringens type A
      and the production of alpha-toxin in vitro was investigated. METHODS AND RESULTS:
      A micro-broth dilution assay was used to evaluate the minimal inhibitory
      concentrations (MIC) of lysozyme against three clinical isolates of Cl.
      perfringens type A in 96-well microtitre plates. The MIC of lysozyme against Cl.
      perfringens isolates was found to be 156 microg ml(-1). Scanning electron
      micrographs of the cells treated with 100 microg ml(-1) of lysozyme revealed
      extensive cell wall damage. A quantitative sandwich ELISA for alpha-toxin
      produced by Cl. perfringens was developed based on a commercial ELISA kit
      allowing only qualitative detection. Addition of 50 microg ml(-1) of lysozyme did
      not inhibit the growth of Cl. perfringens but significantly inhibited the toxin
      production. CONCLUSIONS: Lysozyme inhibited the growth of Cl. perfringens type A
      at 156 microg ml(-1). At sublethal levels, lysozyme was able to inhibit the alpha
      toxin production. SIGNIFICANCE AND IMPACT OF STUDY: Inhibition of Cl. perfringens
      type A and its alpha-toxin production by hen egg white lysozyme had never
      previously been reported. By inhibiting this avian pathogen and its toxin
      production, lysozyme showed potential for use in the treatment and prevention of
      necrotic enteritis and other Cl. perfringens type A related animal diseases.

PMID- 16441379
TI  - The effect of a commercial UV disinfection system on the bacterial load of shell
      eggs.
AB  - AIMS: To study the effect of UV irradiation on the bacterial load of shell eggs
      and of a roller conveyor belt. METHODS AND RESULTS: The natural bacterial load on
      the eggshell of clean eggs was significantly reduced by a standard UV treatment
      of 4.7 s; from 4.47 to 3.57 log CFU per eggshell. For very dirty eggs no
      significant reduction was observed. Eggs inoculated with Escherichia coli and
      Staphylococcus aureus (4.74 and 4.64 log CFU per eggshell respectively) passed
      the conveyor belt and were exposed to UV for 4.7 and 18.8 s. The reduction of
      both inoculated bacteria on the eggshell was comparable and significant for both
      exposure times (3 and 4 log CFU per eggshell). Escherichia coli was reduced but
      still detectable on the conveyor rollers. The internal bacterial contamination of
      eggs filled up with diluent containing E. coli or S. aureus was not influenced by
      UV irradiation. CONCLUSIONS: There is a significant lethal effect of UV
      irradiation on the bacterial contamination of clean eggshells and recent shell
      contamination, contamination of rollers can be controlled and the internal
      contamination of eggs is not reduced. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      penetration of UV into organic material appears to be poor and UV disinfection
      can be used as an alternative for egg washing.

PMID- 16441380
TI  - Detection of Salmonella enterica serovar Typhi (S. Typhi) by selective
      amplification of invA, viaB, fliC-d and prt genes by polymerase chain reaction in
      mutiplex format.
AB  - AIMS: Development of a PCR assay that can target multiple genes for rapid
      detection of Salmonella enterica serovar Typhi (S. Typhi) from water and food
      samples. METHODS AND RESULTS: PCR primers for invasion, O, H and Vi antigen
      genes, invA, prt, fliC-d and viaB were designed and used for the rapid detection
      of S. Typhi by multiplex PCR. Internal amplification control, which co-amplified
      with prt primers, was also included in the assay. The results showed that all
      cultures of Salmonella were accurately identified by the assay with no
      nonspecific amplification in other cultures. The assay had 100% detection
      probability when a cell suspension of 10(4) CFU ml(-1) (500 CFU per reaction) was
      used. Salmonella Typhi bacteria were artificially inoculated in the water and
      food (milk and meat rinse) samples and detected by mPCR after overnight pre
      enrichment in buffered peptone water. No Salmonella bacteria could be detected
      from water samples collected from the field by mPCR or standard culture method.
      CONCLUSIONS: The developed mPCR assay provides specific detection of S. Typhi.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Rapid methods for detection of S. Typhi
      from complex environmental matrices are almost nonexistent. The mPCR assay
      reported in this study can be useful to identify S. Typhi bacteria in field
      environmental samples.

PMID- 16441381
TI  - Effect of plant growth promoting rhizobacteria containing ACC-deaminase on maize
      (Zea mays L.) growth under axenic conditions and on nodulation in mung bean
      (Vigna radiata L.).
AB  - AIMS: This study was conducted to test the hypothesis that the bacterial strains
      possessing 1-aminocyclopropane-1-carboxylic acid (ACC)-deaminase activity may
      also promote growth of inoculated plants and could increase nodulation in legumes
      upon co-inoculation with rhizobia. METHODS AND RESULTS: Several rhizobacteria
      were isolated from maize rhizosphere through enrichment on ACC as a sole N
      source. Purified isolates were screened for growth promotion in maize under
      axenic conditions and for in vitro ACC-deaminase activity. A significant positive
      correlation was observed between in vitro ACC-deaminase activity of bacterial
      cells and root elongation. None of the isolates produced auxins. Bradyrhizobium
      japonicum produced less amount of auxins but did not carry ACC-deaminase
      activity. Results of pot experiment revealed that co-inoculation with
      Bradyrhizobium and plant growth promoting rhizobacteria (PGPR) isolates enhanced
      the nodulation in mung bean compared with inoculation with Bradyrhizobium alone.
      CONCLUSIONS: It is highly expected that inoculation with rhizobacteria containing
      ACC-deaminase hydrolysed endogenous ACC into ammonia and alpha-ketobutyrate
      instead of ethylene. Consequently, root and shoot growth as well as nodulation
      were promoted. SIGNIFICANCE AND IMPACT OF THE STUDY: The ACC-deaminase trait
      could be employed as an efficient tool to screen effective PGPR, which could be
      successfully used as biofertilizers to increase the growth of inoculated plants
      as well as nodulation in legumes.

PMID- 16441382
TI  - Heat resistance of coliform species isolated from cooked ham, snail flesh, and
      'bouchees a la reine'.
AB  - AIMS: In this study, the heat resistance of coliform species isolated from cooked
      ham and ready-made meals was determined. METHODS AND RESULTS: Thirteen coliform
      strains belonging to 12 different species were studied using laboratory medium in
      order to determine delta (first decimal reduction time) and z(T) values
      (temperature increase leading to a 10-fold reduction of delta) using the Weibull
      model. For seven strains, delta-values were determined at temperatures ranging
      from 55 to 60 degrees C, with, delta values between 0.52 and 2.98 min, at 59
      degrees C. For the other six strains, lower temperature values were determined
      with delta-values ranging from 0.47 to 1.64 min at 54 degrees C. z(T) values
      calculated for the 13 strains were 3.1 to 7.5 degrees C. For eight strains,
      plotting of the log of survivors was not linear but rather showed shoulders or
      shoulders and tails. CONCLUSIONS: Coliform species were sensitive to heat
      treatment with a decimal reduction time under 2 min at 60 degrees C. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The better knowledge of coliform heat resistance by
      determining thermal resistance parameters with confidence intervals will be
      useful for evaluating the efficiency of industrial thermal processes.

PMID- 16441383
TI  - PCR/DGGE and 16S rRNA gene library analysis of the colonic microbiota of HLA
      B27/beta2-microglobulin transgenic rats.
AB  - AIMS: To determine the phylogenetic composition of the colonic microbiota of
      transgenic (TG) HLA-B27 rats using 16S ribosomal RNA (rRNA) gene sequences
      obtained from denaturing gradient gel electrophoresis (DGGE) gels and sequences
      from a 16S rRNA gene library. METHODS AND RESULTS: Colonic microbiota of TG and
      nontransgenic (NT) rats harboured by 10-week-old and 6-month-old animals was
      screened using PCR/DGGE. Six months old TG rats had marked inflammation of the
      colon compared with 10-week-old TG and NT rats. The DGGE profiles of rats with
      inflamed colon were similar from rat to rat (Dice's Similarity Coefficient
      proximal colon 73%, distal colon 83%) whereas profiles from animals without
      inflammation were dissimilar (52-64%). Identifications of bacterial origins of
      16S rRNA gene sequences obtained from DGGE gels (200 bp) and from 16S rRNA clones
      (450 bp) of the colonic microbiota of diseased rats gave sequences most closely
      phylogenetically affiliated with uncultured or unknown bacteria. CONCLUSIONS:
      PCR/DGGE was shown to be an effective method to compare the colonic microbiota
      composition of TG and NT rats relative to the progression of inflammatory
      disease. Sequencing of 16S rRNA gene fragments from DGGE gels or 16S rRNA gene
      clones from a random library showed that uncultured or unknown bacteria were most
      commonly detected by both methods. It can be concluded that it would be better in
      future studies to search for the antigens produced by the gut microbiota against
      which the dysfunctional immune system reacts rather than seek phylogenetic
      associations. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR/DGGE can be used as a
      rapid initial screening method to compare the composition of bacterial
      communities of initially unknown composition that are associated with the
      development of intestinal disease.

PMID- 16441384
TI  - Desiccation responses and survival of Sinorhizobium meliloti USDA 1021 in
      relation to growth phase, temperature, chloride and sulfate availability.
AB  - AIMS: To identify physical and physiological conditions that affect the survival
      of Sinorhizobium meliloti USDA 1021 during desiccation. METHODS AND RESULTS: An
      assay was developed to study desiccation response of S. meliloti USDA 1021 over a
      range of environmental conditions. We determined the survival during desiccation
      in relation to (i) matrices and media, (ii) growth phase, (iii) temperature, and
      (iv) chloride and sulfate availability. CONCLUSIONS: This study indicates that
      survival of S. meliloti USDA 1021 during desiccation is enhanced: (i) when cells
      were dried in the stationary phase, (ii) with increasing drying temperature at an
      optimum of 37 degrees C, and (iii) during an increase of chloride and sulfate,
      but not sodium or potassium availability. In addition, we resolved that the best
      matrix to test survival was nitrocellulose filters. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The identification of physical and physiological factors that
      determine the survival during desiccation of S. meliloti USDA 1021 may aid in (i)
      the strategic development of improved seed inocula, (ii) the isolation, and (iii)
      the development of rhizobial strains with improved ability to survive
      desiccation. Furthermore, this work may provide insights into the survival of
      rhizobia under drought conditions.

PMID- 16441385
TI  - Influence of water activity, temperature and time on mycotoxins production on
      barley rootlets.
AB  - AIMS: The objective of this study was to determine the ochratoxin (OT) and
      aflatoxin (AF) production by three strains of Aspergillus spp. under different
      water activities, temperature and incubation time on barley rootlets (BR).
      METHODS AND RESULTS: Aspergillus ochraceus and Aspergillus flavus were able to
      produce mycotoxins on BR. Aspergillus ochraceus produced ochratoxin A (OTA) at
      0.80 water activity (a(w)), at 25 and 30 degrees C as optimal environmental
      conditions. The OTA production varies at different incubation days depending on
      a(w). Aflatoxin B(1) (AFB1) accumulation was obtained at 25 degrees C, at 0.80
      and 0.95 a(w), after 14 and 21 incubation days respectively. Temperature was a
      critical factor influencing OTA and AFB(1) production. CONCLUSIONS: This study
      demonstrates that BR support OTA and AFB(1) production at relatively low water
      activity (0.80 a(w)) and high temperatures (25-30 degrees C). SIGNIFICANCE AND
      IMPACT OF THE STUDY: The study of ecophysiological parameters and their
      interactions would determine the prevailing environmental factors, which enhance
      the mycotoxin production on BR used as animal feed.

PMID- 16441386
TI  - Editors and publishing: integrity, trust and faith.

PMID- 16441387
TI  - Supplementary prescribing: relationships between nurses and psychiatrists on
      hospital psychiatric wards.
AB  - The purpose of this study was to explore some of the issues for the
      implementation of supplementary prescribing for acute hospital care. The study
      design was the use of focus group methodology. In total, 19 nurses and 7
      psychiatrists joined 1 of 6 focus groups held on the psychiatric unit. The data
      were analyzed using a modified grounded theory technique. In the study to be
      reported here, nurses and psychiatrists described the potential for different
      ways of working to emerge on acute psychiatric wards. Two major themes were
      identified: supplementary prescribing bringing about different ways of
      influencing decisions and controlling professional work; nurses and psychiatrists
      developing different types of relationships. Findings suggest an overall positive
      acceptance for supplementary prescribing, but for greater attention to be placed
      on the nature of relationships between nurses and psychiatrists. Implications for
      practice include the impact on new roles for nurses and psychiatrists and how
      this new form of relationship can best serve patients.

PMID- 16441388
TI  - In search of the true self: a clinical journey through the vale of soul-making.
AB  - Once a person accepts any form of mainstream mental health care, she is faced
      with the paradox of disabling caring. Every time an emotionally distressed
      individual is professionally rescued, she forfeits a golden opportunity to
      discover and utilize her own healing potential. Yet within a mental health
      service that is heavily medicalized and investing more and more in time-limited
      therapies, can it ever be otherwise? Drawing on the developmental theory of
      Donald Winnicott, together with the poet John Keats' concept of 'Soul-making',
      this case study provides an account of therapy delivered from outside the
      parameters of a health-illness model of caring. It acknowledges human suffering
      as a natural and inevitable part of life and, whilst acknowledging the value of
      therapeutic companionship, proclaims the mentally distressed person as best
      placed to navigate her own recovery.

PMID- 16441389
TI  - Aggressive behaviour in the high-secure forensic setting: the perceptions of
      patients.
AB  - Twenty-seven patients undergoing treatment in a high-secure forensic facility
      participated in focus group interviews to elicit their perceptions of (1) the
      factors leading to aggressive behaviour; and (2) strategies to reduce the risk of
      such behaviour. The focus group interviews were audiotaped, transcribed and
      analysed using content analysis. The participants identified that a combination
      of patient, staff and environmental factors contributed to violence in the study
      wards. The cause of aggressive behaviour centred around five major themes: the
      environment; empty days; staff interactions; medication issues; and patient
      centred factors. Potential strategies identified by patients to reduce aggressive
      behaviour included: early intervention; the provision of meaningful activities to
      reduce boredom; separation of acutely disturbed patients; improved staff
      attitudes; implementation of effective justice procedures; and a patient advocate
      to mediate during times of conflict. Findings suggested that social and
      organizational factors need to be addressed to change the punitive subculture
      inherent in forensic psychiatric facilities, and to ensure a balance between
      security and effective therapy.

PMID- 16441390
TI  - Pharmacological management of akathisia in combination with psychological
      interventions by a mental health nurse consultant.
AB  - The article describes the management of akathisia by a mental health nurse (MHN)
      prescriber, working in partnership with the patient. A single-case design was
      used to evaluate this. It highlights three features: first, MHN can safely
      prescribe psychiatric medication in combination with concordance therapy. Second,
      the value base underpinning prescribing practice is partnership, honesty and
      choice for the patient. Finally, the pharmacological mechanism of antipsychotic
      medication, which contributes towards akathisia, requires further analysis.

PMID- 16441391
TI  - Greek psychiatric care reform: new perspectives and challenges for community
      mental health nursing.
AB  - The purpose of this article is twofold: (1) to explore the main issues of
      psychiatric care reform in Greece and outline the operating way of the new
      residential structures of psychiatric care and rehabilitation; and (2) to focus
      on the implementation of mental health nursing roles in the primary care services
      such as supervisor-therapist, liaison, coordinator-crisis interventionist and
      counsellor-trainer within the context of a multidisciplinary therapeutic team.
      Given that multiple professionals are involved in mental health care in primary
      care, issues of role are likely to be crucial to the effective implementation of
      new workers. Moreover, there is existing evidence of ambiguity in the roles of
      different mental health professionals in primary care, relating to the problems
      they manage and the treatments they provide. The authors believe that more
      emphasis needs to be given to the mental health nursing specialty in Greece,
      because the large majority of patients requiring mental health care should have
      the possibility of taking better quality of care as the psychiatric structures at
      community are continuously developing.

PMID- 16441392
TI  - The development of an evaluation questionnaire for the Newcastle Crisis
      Assessment and Home Treatment Service: finding a way to include the voices of
      service users.
AB  - The views of users of services have traditionally been sought through the use of
      'patient satisfaction' surveys. Because such surveys are often devised by service
      providers there are concerns that their use as evaluation tools may be flawed due
      to issues of power and passivity, and that they do not represent active
      involvement by service users in the feedback loop. The Newcastle Crisis
      Assessment and Treatment Service offers treatment at home to people in mental
      health crisis who would otherwise be admitted to hospital. This article reports
      on the process of inviting previous users of a home treatment service to give
      their views about what was most important to them about receiving the service. A
      participatory research approach combining a two-stage modified Delphi study and
      semi-structured interviews conducted by service user interviewers were employed
      to gather rich data to inform the construction of a service evaluation
      questionnaire. The questionnaire is now in routine use for every person who is in
      receipt of treatment at home. The feedback obtained from the questionnaire will
      be used to shape and refine the service provided by the team. As a 'live'
      document through use and feedback, the questionnaire will continue to evolve in
      order to retain its sensitivity and relevance.

PMID- 16441393
TI  - Proposed changes to the Mental Health Act of England and Wales: research
      indicating future educational and training needs for mental health nurses.
AB  - Proposed changes to the Mental Health Act (MHA) legislation in England and Wales
      have been identified as having significant impact upon both mental health service
      delivery and professional roles. Key issues being identified for both service
      delivery and professionals are the creation of approved mental health
      professionals (AMHP), increased demand upon community services and a potential
      negative impact upon the therapeutic relationship. Mental health nurses in
      particular have expressed their concerns, through their professional bodies,
      regarding the impact of the proposed MHA changes upon the therapeutic
      relationship. The aim of this article is to present findings from recently
      conducted research that explores experiences and perceptions of approved social
      workers (ASWs) regarding the impact of invoking the MHA upon the therapeutic
      relationship. These findings inform wider mental health nursing practice of
      essential skills and knowledge to protect and potentially enhance the therapeutic
      relationship while invoking MHA legislation. A questionnaire was distributed to
      ASWs working within the Trent region. The questionnaire included both closed and
      open questions inviting respondents to expand upon their experiences with the
      brief initial findings being earlier published. Semi-structured interviews with
      eight invited respondents to develop their responses were undertaken enabling an
      approach that was both conversational and emergent.

PMID- 16441394
TI  - Further thoughts on the process of restraint.
AB  - The physical restraint of a disturbed person is a subject constant of psychiatry
      and is a challenge that particularly faces nurses working in acute inpatient
      settings. While other approaches to psychiatric treatment have been discarded
      (e.g. punishment, blood letting, trepanation, deep insulin therapy and so on) or
      evolved into new treatments (the use of medication), the act of physical
      restraint has remained largely unmodified. Given the ubiquity of physical
      restraint in psychiatry, particularly as a nursing procedure, the absence of a
      sustained body of research is notable. This essay examines some of the historical
      underpinnings of the use of restraint in psychiatry brought into sharp focus by
      the David Bennett Inquiry Report (2003) and the National Institute of Clinical
      Effective (NICE) guidelines (2005) on the management of violence.

PMID- 16441395
TI  - Conceptions of patients and personnel concerning the substance of post-ward
      outpatient visits in psychiatric care.
AB  - In post-ward outpatient services patients discharged from hospital are provided
      further care by the same ward personnel. The aim of this study was to describe
      and analyse the conceptions concerning the substance of post-ward outpatient
      visits (PWOV). A phenomenographic approach was used. The data were gathered by
      interviewing post-ward outpatients, personnel at psychiatric wards and in
      outpatient care and administrative personnel in psychiatric units. Seven main
      categories of describing the PWOV were formed: natural interaction, continuous
      assessment, follow-up of the implementation of pharmacotherapy, relapse
      prevention, search for coping methods, establishing motivation for treatment and
      family members' participation in care. The patient's health, life situation and
      coping in everyday life were constantly evaluated and followed up in diverse ways
      during the PWOV. To make PWOV successful, treatment should be planned
      individually based on the patient's needs, and the patient should have a close
      and functional cooperative relationship with the nurse.

PMID- 16441396
TI  - Service users and other stakeholders' evaluation of a liaison mental health
      service in an accident and emergency department and a general hospital setting.
AB  - Liaison mental health care has been an emerging specialism of mental health
      nursing in the UK since the early 1990s. Studies have so far looked only briefly
      at service user evaluation. A qualitative study involving 47 interviews with
      service user and professional stakeholders was undertaken to determine what is
      important to stakeholders in a liaison mental health-care service. The largest
      group of stakeholders interviewed were service users. Analysis of the data was
      undertaken using the service user interviews to guide the development of themes.
      The majority of the issues identified were raised by both service users and
      professionals. The three key themes were, the practicalities of the service
      including waiting time, the staffing profile and receiving the service, which
      included issues such as the opportunity to talk and outcomes. The findings
      provide new information regarding what service users and other stakeholders
      expect from a liaison mental health service and important areas to consider when
      offering a satisfactory service.

PMID- 16441397
TI  - The role of the nurse practitioner in psychiatric/mental health nursing:
      exploring consumer satisfaction.
AB  - There is a substantial body of literature pertaining to the role of the nurse
      practitioner. Research directed towards consumer satisfaction suggests that the
      care provided by nurse practitioners is perceived as at least equal to that
      provided by a medical practitioner. However, there is a paucity of literature
      examining the nurse practitioner role in the psychiatric/mental health field. An
      evaluation of a Nurse Practitioner demonstration model has recently been
      undertaken in the Crisis, Assessment and Treatment Team in Victoria, Australia.
      This article presents the findings of a qualitative, exploratory study.
      Individual interviews were conducted with consumers (n = 7) who had received care
      and treatment provided by the nurse practitioner candidate. Data analysis
      revealed two main themes: the quality of the service provided, and the unique
      role of the nurse. The findings supported the available literature in
      articulating the specific aspects of the nurse practitioner role that are
      favourably perceived by consumers of services. This study contributes to the
      limited body of knowledge in the psychiatric/mental health nursing field and
      specifically emphasizes the importance of the relationship between nurse
      practitioner and consumer in facilitating the provision of effective care and
      treatment.

PMID- 16441398
TI  - Undergraduate nursing students' perceptions of substance use and misuse: a
      Brazilian position.
AB  - Alcohol, cocaine and cannabis are the substances most commonly abused in Brazil.
      There is limited evidence on the perceptions of undergraduate nursing students
      towards substance misuse. Negative attitudes, in combination with the lack of
      appropriate knowledge and skills, may result in minimal care provided to
      substance misusers. The aims of the study are to examine the knowledge and
      attitudes of undergraduate nursing students towards substance misusers and
      consider the implications of these attitudes for nursing education. The Nurse
      Education in Alcohol and Drug Educational Faculty Survey (NEADA) questionnaire on
      knowledge and education, nursing interventions, attitudes and values was
      distributed to undergraduate nurses (n = 227) in the south and south-eastern part
      of Brazil. The findings showed that there is a lack of adequate education in drug
      and alcohol use and misuse, including competency skills, but the participants
      were positive about treatment interventions. A paradigm shift in nurse education
      curricula and further research studies on attitudes and values towards substance
      misuse should be on the educational agenda. These are challenges faced by nurses
      to meet the healthcare needs of substance misusers.

PMID- 16441399
TI  - Clinician perceptions of personal safety and confidence to manage inpatient
      aggression in a forensic psychiatric setting.
AB  - Inpatient mental health clinicians need to feel safe in the workplace. They also
      require confidence in their ability to work with aggressive patients, allowing
      the provision of therapeutic care while protecting themselves and other patients
      from psychological and physical harm. The authors initiated this study with the
      predetermined belief that a comprehensive and integrated organizational approach
      to inpatient aggression was required to support clinicians and that this approach
      increased confidence and staff perceptions of personal safety. To assess
      perceptions of personal safety and confidence, clinicians in a forensic
      psychiatric hospital were surveyed using an adapted version of the Confidence in
      Coping With Patient Aggression Instrument. In this study clinicians reported the
      hospital as safe. They reported confidence in their work with aggressive
      patients. The factors that most impacted on clinicians' confidence to manage
      aggression were colleagues' knowledge, experience and skill, management of
      aggression training, use of prevention and intervention strategies, teamwork and
      the staff profile. These results are considered with reference to an expanding
      literature on inpatient aggression. It is concluded that organizational
      resources, policies and frameworks support clinician perceptions of safety and
      confidence to manage inpatient aggression. However, how these are valued by
      clinicians and translated into practice at unit level needs ongoing attention.

PMID- 16441400
TI  - 'Disgust, disgust beyond description'- shame cues to detect shame in disguise, in
      interviews with women who were sexually abused during childhood.
AB  - Shame is a recurrent theme in the context of sexually abused women. Sexual abuse
      is taboo and shameful, and so is shame. Shame affects the development of a person
      and relationships, and is mentally painful. It is often covert. One aim of the
      present study was to explore whether and how women exposed to sexual abuse during
      childhood verbally express unacknowledged overt and covert shame, when
      interviewed about their physical and mental health, relations and circumstances
      relating to the sexual abuse. Another aim was, if shame was present, to describe
      the quality of the shame expressed by the women. A mainly qualitative approach
      with semi-structured interviews was used. Ten women attending self-help groups
      for women who were sexually abused during childhood were recruited as informants.
      The interviews were analysed for verbal expressions of shame by identifying code
      words and phrases, which were first sorted into six shame indicator groups and
      then categorized into various aspects of shame. The frequency of the code words
      and phrases was also counted. The findings clearly reveal that the affect of
      shame is present and negatively influences the lives of the informants in this
      study. It was possible to sort the code words and phrases most often mentioned
      into the indicator groups 'alienated', 'inadequate' and 'hurt', in the order of
      their frequency. It is obvious that shame affects the lives of this study's
      informants in negative ways. One important clinical implication for professionals
      in health care and psychiatric services is to acknowledge both sexual abuse and
      shame in order to make it possible for patients to work through it and thereby
      help them psychologically to improve their health.

PMID- 16441401
TI  - Patients' perspectives on information received in outpatient psychiatry.
AB  - The purpose of this study is to develop a scale in order to determine the
      informational needs deemed most important by psychiatric outpatients, and to
      determine their level of satisfaction with information received. The 'Patients'
      Perspective on Information Questionnaire' (PPIQ) scale was created and given to a
      volunteer sample of 86 psychiatric outpatients. The Client satisfaction
      questionnaire (CSQ-8), assessing global satisfaction, was also completed to
      assess the convergent validity of the PPIQ-Satisfaction subscale. Internal
      consistency for the two PPIQ subscales (Information and Satisfaction) is
      excellent (alpha = 0.90 and 0.91). Convergent validity between the Satisfaction
      subscale and the CSQ is adequate (r = 0.5). The PPIQ reveals high importance
      ratings given to items such as 'side effects of medication' and 'confidentiality
      and access to chart'. Elevated satisfaction ratings are given to items from the
      conceptual category 'treatment information'. Dissatisfaction on the PPIQ is
      highest for components of 'information on service modality and organization'. The
      PPIQ appears to distinguish between information that is important to clients and
      their level of satisfaction with that information. Satisfaction on multiple
      components of information, such as treatment, service modality and organization,
      and clinical difficulties should be assessed to generate feedback to improve
      services.

PMID- 16441402
TI  - Dual diagnosis and forensic care. Are the needs of service users being met?

PMID- 16441405
TI  - Expression patterns of hair and epithelial keratins and transcription factors
      HOXC13, LEF1, and beta-catenin in a malignant pilomatricoma: a histological and
      immunohistochemical study.
AB  - BACKGROUND: We have previously shown that benign pilomatricomas not only maintain
      the sequential expression of the hair matrix and precortex keratins hHa5 and hHa1
      of normal hair follicles in their transitional cell compartment, but also
      preserve the association of hHa5 expression with that of its regulatory
      homeoprotein HOXC13 in the lower transitional cell compartment. In contrast, hHa1
      expression in the upper transitional cell compartment is uncoupled from the
      nuclear co-expression of the LEF1/beta-catenin complex seen in normal hair
      follicles (Cribier et al., J Invest Dermatol 2004; 122: 1078). METHODS: Formalin
      fixed paraffin sections of the tumor were examined using a panel of mono- and
      polyclonal hair and epithelial keratin antibodies as well as antibodies against
      HOXC13, LEF1, and beta-catenin. RESULTS: Morphologically, the malignant
      pilomatricoma investigated here clearly deviated from the described major tumor
      type by a large number of differently sized parakeratotic squamoid whorls
      emerging within the mass of basaloid cells and surrounded by cells remembering
      transitional cells, but only rarely containing shadow cells and signs of
      calcification. We show that hHa5/HOXC13 co-expression was maintained in
      transitional cell areas, in which hHa1 expression was much stronger than in
      benign pilomatricomas, but again uncoupled from concomitant nuclear LEF1/beta
      catenin expression. Surprisingly, however, and in clear contrast to benign
      pilomatricomas, these transitional cells co-expressed the epithelial keratins K5,
      K14, and K17, with the latter being as strongly expressed as hHa1, both also
      staining the entire inner mass of the parakeratotic whorls. CONCLUSIONS: Although
      the malignant pilomatricoma investigated here was distinctive in that it
      contained a multitude of parakeratinizing whorls and no signs of calcification,
      it shared both hHa5/HOXC13 co-expression and disrupted hHa1/beta-catenin-LEF1
      expression in its transitional cell compartment around the whorls with benign
      pilomatricomas. However, in clear contrast to the latter, transitional cells of
      the malignant tumor also strongly expressed the epithelial keratins K5, K14, and
      K17. We speculate that the observed dominance of the epithelial differentiation
      pathway over the competing conventional shadow cell differentiation pathway may
      prevent massive calcification of the tumor.

PMID- 16441406
TI  - Expression of retinoid receptors in sebaceous cell carcinoma.
AB  - PURPOSE: The aim of this study is to investigate whether there are any
      abnormalities in the in vivo expression of retinoid acid receptors (RAR-alpha,
      RAR-beta and RAR-gamma) and retinoid X receptors (RXR-alpha, RXR-beta and RXR
      gamma) in sebaceous cell carcinoma. METHODS: Expression of retinoid receptors in
      paired specimens of cancerous tissues (n = 10) and adjacent normal tissues (n =
      10) from 10 patients with sebaceous cell carcinoma was studied
      immunohistochemically by using anti-retinoid receptor antibodies. RESULTS: In
      eight of the 10 normal tissue samples, all six receptors were expressed. In the
      other two samples, all receptors were expressed except RAR-gamma (one sample) or
      RXR-gamma (two samples). Five tumours (50%) lacked RAR-alpha; RAR-alpha
      expression was lower in tumours than in normal tissues in eight of 10 cases. RAR
      beta was expressed in the cytoplasm of nine of 10 tumours; RAR-beta expression
      was at least as high in tumours as in normal tissue in eight of 10 cases. Two
      tumours lacked RAR-gamma; three tumours had lower RAR-gamma expression than
      paired normal epithelium; four had the same RAR-gamma expression, and one had
      higher RAR-gamma expression. RXR-alpha expression was strong in all normal
      tissues and tumour samples. Ten tumours lacked RXR-beta and all 10 tumours lacked
      RXR-gamma expression. CONCLUSIONS: Diminished RXR-beta and RXR-gamma expression
      might be related to the development of sebaceous cell carcinoma. Additional
      studies are required to establish whether the defects in RAR expression in
      sebaceous cell carcinoma might affect the potential response of this tumour to
      treatment with retinoids.

PMID- 16441407
TI  - Histopathologic spectrum of erythema nodosum.
AB  - Erythema nodosum (EN) is the most common panniculitis and histologically
      represents the prototype of a septal panniculitis. However, the histologic
      findings can be quite variable. We describe four patients with EN who each
      underwent two consecutive biopsies. In each case, the first biopsy showed
      histopathologic features that fall outside the usual spectrum of disease. Two
      cases showed predominantly neutrophilic infiltrates with focal suppuration as
      well as vasculitis of medium-sized arteries. The areas of suppuration were more
      extensive in the first case prompting special stains for microorganisms that were
      all negative. The third case demonstrated a lobular panniculitis with a
      predominantly lymphohistiocytic infiltrate. Special stains were negative in this
      case as well. The fourth case revealed vasculitis of a medium sized artery, small
      vessel vasculitis, and a mixed septal and lobular panniculitis with a polyclonal
      population of atypical lymphocytes. In all patients, the clinical course and the
      subsequent biopsy were classic for EN. We conclude that lobular neutrophilic
      panniculitis with suppuration, small vessel vasculitis, and even medium vessel
      arteritis may rarely occur in EN. There are few clues in these unusual cases that
      allow for a specific diagnosis from the start, and often, a second biopsy is
      required.

PMID- 16441408
TI  - Expression of Bcl-x in normal skin and benign cutaneous adnexal tumors.
AB  - BACKGROUND: Bcl-x appears to have an antiapoptotic role in the epidermis. Little
      is known about the expression of Bcl-x in cutaneous adnexal structures and benign
      cutaneous adnexal tumors. METHODS: Tissues from 31 cases of benign cutaneous
      adnexal tumors (five trichofolliculomas, five trichoepitheliomas, two sebaceous
      adenomas, five apocrine hidradenomas, five eccrine poromas, five eccrine
      spiradenomas, and four syringomas) were immunostained for Bcl-x. RESULTS: Strong
      staining for Bcl-x was seen in cells of the epidermal granular layer and inner
      root sheath of hair follicles. Sebaceous gland cells showed strong staining.
      Apocrine gland cells showed weak to moderate staining. No staining was seen in
      eccrine gland cells. The basaloid cells of trichofolliculomas and
      trichoepitheliomas showed no staining. In sebaceous adenomas, the sebaceous cells
      showed strong staining while the basaloid cells were negative. The cells of
      apocrine hidradenomas showed patchy weak staining. No staining was seen in
      eccrine poromas, eccrine spiradenomas, and syringomas. CONCLUSIONS: The degree of
      Bcl-x expression in cutaneous adnexal glandular structures appears to be related
      to their mode of secretion, being strongest in cells with apoptotic degradation
      of the entire cell (sebocytes). This pattern is recapitulated in the
      corresponding benign cutaneous adnexal tumors. Bcl-x may be useful in identifying
      cells with sebaceous differentiation in poorly differentiated adnexal tumors.

PMID- 16441409
TI  - Expression of c-kit (CD117) in Spitz nevus and malignant melanoma.
AB  - BACKGROUND: CD117, the receptor for kit-ligand, which is a growth factor for
      melanocyte migration and proliferation, has shown differential staining in
      various benign and malignant melanocytic lesions. The purpose of this study is to
      compare CD117 immunohistological staining in Spitz nevus versus malignant
      melanoma, to determine whether CD117 can aid in the diagnosis of these two
      lesions. METHODS: CD-117 immunohistological staining was performed in 22
      clinically and pathologically diagnosed pigmented lesions including 9 cases of
      Spitz nevus, 10 cases of primary MM and 3 cases of metastatic melanoma. RESULTS:
      There was no significant difference in CD117 staining in either epidermis or
      dermis between Spitz nevi and primary melanomas. However staining of metastatic
      melanomas is less than dermal staining of primary MM and Spitz nevus.
      CONCLUSIONS: CD117 is unlikely a useful diagnostic tool in differentiating Spitz
      nevus from primary MM. On the other hand, CD 117 may be useful in differentiating
      metastatic melanoma from primary melanoma in patients who had a history of
      melanoma and who present with new dermal lesions.

PMID- 16441410
TI  - Macrophage-rich epithelioid angiosarcoma mimicking malignant melanoma.
AB  - BACKGROUND: Cutaneous epithelioid angiosarcoma is a type of cutaneous
      angiosarcoma and usually arise both on the head or neck of the elderly. CASE
      REPORT: An 86-year-old male with an epithelioid angiosarcoma of the scalp that
      mimicked malignant melanoma. RESULTS: A large irregular dark grey-blue plaque
      with an adjacent speckled tan nodule was suggestive of a primary cutaneous
      malignant melanoma with adjacent in-transit metastasis. Both had a well
      circumscribed growth pattern and were composed of numerous large epithelioid
      cells with scattered severe atypia and mitoses. The tumor was positive for S-100
      protein and vimentin and negative for low- and high-molecular weight
      cytokeratins. However, at high power, the epithelioid cells with severe atypia
      were negative for S-100 protein, and abundant large epithelioid macrophages were
      responsible for the S-100 protein positivity. The malignant tumor cells were
      negative for HMB-45, positive for CD31 and Factor VIII-related antigen, and
      focally positive for CD34. A focus of infiltrative, classical angiosarcoma with
      irregular vascular channels lined with plump, anaplastic endothelial cells was
      then found deep to the epithelioid tumor. CONCLUSIONS: Macrophage-rich
      epithelioid angiosarcoma demonstrates abundant S-100 protein-positive epithelioid
      macrophages. This subset of epithelioid angiosarcoma may mimic malignant melanoma
      and may present as a pitfall in diagnosis.

PMID- 16441411
TI  - Adenosis tumor of anogenital mammary-like glands: a case report and demonstration
      of clonality by HUMARA assay.
AB  - In mammary pathology, adenosis tumor is defined as a clinically recognizable
      lesion that histologically primarily consists of adenosis, but also exhibits
      various combinations of diverse epithelial changes seen in other benign breast
      diseases. A lesion that occurred in the anogenital area of a 46-year-old woman
      and apparently arose in anogenital mammary-like glands is described and which, in
      our opinion, is best classified as adenosis tumor. A biopsy revealed a well
      demarcated, unencapsulated lesion surrounded by compressed fibrous tissue forming
      a pseudocapsule. Several histological patterns within the same tumor mass were
      recognizable: sclerosing adenosis-like changes, variably sized microcysts and
      cysts, some with rare short papillary projections having hyalinized cores, rare
      tubular structures exhibiting epithelial features reminiscent of simple ductal
      hyperplasia, areas with oxyphilic (apocrine) metaplasia, and clear cell
      epithelial changes resembling mucinous metaplasia. Decapitation secretion was
      notable in many lumens. Rare lumens were filled with foamy macrophages. There
      were also focal clear cell changes of myoepithelial cells. The stroma was
      paucicellular and sclerotic in some foci and composed of myofibroblasts and
      myxoid in others. Calponin, actins, and p63 stained myoepithelial cells. The
      cells in the oxyphilic (apocrine) metaplasia areas stained for mitochondrial
      antigen and Bcl-2. Antibodies to progesterone and estrogen receptor stained
      approximately 50 and 20% of the epithelial cell population, respectively. Human
      androgen receptor gene analysis yielded a monoclonal pattern. As our case
      exhibited a number of patterns identical to those seen in diverse benign breast
      diseases, its classification as adenosis tumor seems justifiable. This cutaneous
      perianal lesion is indistinguishable microscopically from its mammary analogue
      and was clinically detectable.

PMID- 16441412
TI  - Pure sclerotic neurofibroma: a neurofibroma mimicking sclerotic fibroma.
AB  - BACKGROUND: Neurofibroma (NF) is a benign tumor of the nerve sheath. Several
      variants of NF have been described. PURPOSE: We report a case of NF with
      sclerotic changes resembling sclerotic fibroma (SF). METHODS AND RESULTS: The
      patient was a 61-year-old man who had an asymptomatic cutaneous lesion on the
      right scapular region. Physical examination revealed a pedunculated, white-to
      pinkish nodule that had a firm consistency, spherical morphology, and smooth
      surface. Microscopically, the nodule showed a well-circumscribed, nonencapsulated
      dermal tumor composed of scant cells and thick collagen bundles with prominent
      clefts. The tumor cells were immunoreactive for vimentin and S100 protein. The
      patient was diagnosed as having pure sclerotic NF. To our knowledge, only five
      cases of NF with SF-like pattern have been previously published, and in two this
      pattern was pure. CONCLUSION: It is important to recognize this exceptional type
      of NF because it may be easily confused with SF, as well as with a wide variety
      of neoplasms or hamartomatous conditions containing similar sclerotic pattern.

PMID- 16441413
TI  - Multiple cellular neurothekeomas--a case report and review on the role of
      immunohistochemistry as a histologic adjunct.
AB  - BACKGROUND: Cellular neurothekeoma is a relatively rare, benign cutaneous
      neoplasm, which usually presents as a solitary papule or nodule involving the
      head and neck area of young adults. Multiple neurothekeomas have not, to date,
      been known to occur. METHODS: We report a 30-year-old, otherwise healthy, male
      who presented with multiple neurothekeomas (15) in the head and neck area over a
      period of 12 years. RESULTS: While the unifying feature of all biopsied (10 of
      15) lesions was the presence of epithelioid cells--the lesions differed in their
      cellularity and the degree of sclerosis of the stromal component. Antigenic
      profiling of the lesional cells revealed expression of vimentin, NKI/C3, PGP 9.5,
      factor XIIIa and CD68 but not S100, HMB45, MelanA, EMA, MSA, desmin, CD57 or NGF
      R. CONCLUSIONS: This case report is the first to document the occurrence of
      multiple cellular neurothekeomas. An unusual histologic feature of some of the
      biopsied lesions was the presence of a markedly sclerotic stroma.

PMID- 16441414
TI  - Interpretation and recollection different.

PMID- 16441416
TI  - Primary mucinous carcinoma of the skin.

PMID- 16441418
TI  - Laminin-5 (laminin-332): Unique biological activity and role in tumor growth and
      invasion.
AB  - The development and progression of tumor cells is controlled by their
      interactions with neighboring host cells and a variety of microenvironmental
      factors including extracellular matrix (ECM) molecules, growth factors and
      proteinases. Cell-adhesive ECM proteins are a prerequisite for growth and
      migration of many types of cells. Their interactions with integrins and other
      cell surface receptors induce intracellular signaling that regulates the actin
      cytoskeleton and gene expression. The basement membrane protein laminin-5 is a
      notable cell adhesion molecule, which promotes cellular adhesion and migration
      much more efficiently than other ECM proteins. There is accumulating evidence
      that laminin-5 is involved in tumor growth and progression. With special
      reference to laminin-5, this article reviews the regulatory mechanisms of
      cellular adhesion and migration by ECM molecules and their significance in tumor
      progression.

PMID- 16441419
TI  - Formation of 8-hydroxy-2'-deoxyguanosine in the DNA of cultured human
      keratinocytes by clinically used doses of narrowband and broadband ultraviolet B
      and psoralen plus ultraviolet A.
AB  - Psoralen plus ultraviolet A (PUVA) and narrowband ultraviolet B (UVB) are widely
      used in skin disease phototherapy. Recently, the efficacy of UVB therapy has been
      greatly improved by narrowband UVB, compared to conventional broadband UVB. The
      objectives of the current study were to evaluate the influence of UVB-induced and
      PUVA-induced oxidative stress on cultured keratinocytes. We analyzed 8-hydroxy-2'
      deoxyguanosine (8-OH-dG) in human keratinocytes (HaCaT cell line) using a high
      performance liquid chromatography system equipped with an electrochemical
      detector. Non-irradiated human keratinocytes contained a baseline of 1.48 +/-
      0.22 (mean +/- SD) 8-OH-dG per 10(6) deoxyguanosine (dG) residues in cellular
      DNA, which increased linearly with higher doses of UVB. When their abilities to
      induce 8-OH-dG were compared to each other, based on the minimal erythemal and
      therapeutically used doses, by irradiating them with broadband UVB at 100
      mJ/cm(2), the amount of 8-OH-dG increased to 3.42 +/- 0.46 residues per 10(6) dG,
      while a narrowband UVB treatment at 1000 mJ/cm(2), with biological effects
      comparable to those elicited by 100 mJ/cm(2) broadband UVB, increased it to 2.06
      +/- 0.31 residues per 10(6) dG. PUVA treatment, with 100 ng/mL 8-methoxypsoralen
      and 5000 mJ/cm(2) UVA, increased the 8-OH-dG level to 4.52 +/- 0.42 residues per
      10(6) dG. When HaCaT cells treated with 2000 mJ/cm(2) narrowband UVB were
      cultured and the amount of 8-OH-dG was monitored in the living cells, 65.6% of
      the residues were repaired 24 h after treatment. Our study provides a warning
      that widely used narrowband UVB and PUVA induce cellular oxidative DNA damage at
      the therapeutically used doses, although to a lesser degree than broadband UVB
      with the same clinically effective dose.

PMID- 16441420
TI  - Phenotypic characterization of endometrial stromal sarcoma of the uterus.
AB  - Endometrial stromal sarcoma (ESS) of the uterus is a rare uterine malignancy that
      has not been characterized in detail. To characterize the phenotype of ESS of the
      uterus, we extracted RNA from ESS and the stroma of normal endometrium using a
      tissue microdissection system and compared the expression profiles in the two
      tissues. After suppression subtractive hybridization and differential screening,
      we detected the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1)
      gene as one of the major genes upregulated in ESS, and a full-length placental
      cDNA clone (CS0DI066YJ10) as one of the major genes downregulated. The results
      were confirmed by in situ hybridization in four resected specimens of ESS and 36
      biopsy specimens of normal endometrial tissue. All ESS (4/4) and all cases of
      endometrial stromal cells in the proliferative phase (13/13) were positive for
      MALAT-1, but samples of normal stroma in the secretory phase and menopausal state
      included some that were negative or weakly positive for MALAT-1 (5/13 and 3/10,
      respectively). In contrast, all ESS and 12 of 13 cases of stromal cells in the
      proliferative phase were negative for the full-length placental cDNA clone but 10
      of 13 cases of endometrial stromal cells in the secretory phase were positive for
      transcripts of the gene (P < 0.05). These results indicated that endometrial
      stromal cells have different phenotypic characteristics between proliferative and
      secretory phases and the tumor cells of ESS have the phenotypic character of
      endometrial stromal cells in the proliferative phase.

PMID- 16441421
TI  - Enhanced SMYD3 expression is essential for the growth of breast cancer cells.
AB  - We previously reported that upregulation of SMYD3, a histone H3 lysine-4-specific
      methyltransferase, plays a key role in the proliferation of colorectal carcinoma
      (CRC) and hepatocellular carcinoma (HCC). In the present study, we reveal that
      SMYD3 expression is also elevated in the great majority of breast cancer tissues.
      Similarly to CRC and HCC, silencing of SMYD3 by small interfering RNA to this
      gene resulted in the inhibited growth of breast cancer cells, suggesting that
      increased SMYD3 expression is also essential for the proliferation of breast
      cancer cells. Moreover, we show here that SMYD3 could promote breast
      carcinogenesis by directly regulating expression of the proto-oncogene WNT10B.
      These data imply that augmented SMYD3 expression plays a crucial role in breast
      carcinogenesis, and that inhibition of SMYD3 should be a novel therapeutic
      strategy for treatment of breast cancer.

PMID- 16441422
TI  - Clinical utility of quantitative RT-PCR targeted to alpha1,4-N
      acetylglucosaminyltransferase mRNA for detection of pancreatic cancer.
AB  - alpha1,4-N-Acetylglucosaminyltransferase (alpha4GnT) is a glycosyltransferase
      responsible for the biosynthesis of alpha1,4-GlcNAc-capped O-glycans, and is
      frequently expressed in pancreatic cancer cells but not peripheral blood cells.
      In the present study, we tested the clinical utility of alpha4GnT mRNA expressed
      in the mononuclear cell fraction of peripheral blood as a biomarker of pancreatic
      cancer. Total RNA isolated from the peripheral blood mononuclear cells from 55
      pancreatic cancer patients, 10 chronic pancreatitis patients, and 70 cancer-free
      volunteers was analyzed quantitatively by reverse transcription-polymerase chain
      reaction with primers specific for alpha4GnT, and the expression level of
      alpha4GnT mRNA relative to that of glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) was measured. When the ratio of alpha4GnT to GAPDH transcripts exceeded a
      defined cut-off value, patients were considered to have pancreatic cancer. By
      these standards, 76.4% of the pancreatic cancer patients were detected by this
      assay. A strong correlation was obtained between positivity in this assay and the
      expression of alpha4GnT protein detected immunohistochemically in pancreatic
      cancer tissues resected subsequently, suggesting that alpha4GnT mRNA detected in
      the peripheral blood is derived from circulating pancreatic cancer cells.
      Although increased levels of alpha4GnT mRNA was detected in 40.0% of chronic
      pancreatitis patients and 17.1% of cancer-free volunteers, the expression levels
      were significantly lower than those seen in pancreatic cancer patients. These
      results suggest that quantitative analysis of alpha4GnT mRNA expressed in the
      mononuclear cell fraction of peripheral blood will contribute to the detection of
      pancreatic cancer.

PMID- 16441423
TI  - Immunohistochemical and genetic features of gastric and metastatic liver
      gastrointestinal stromal tumors: sequential analyses.
AB  - Metastatic gastrointestinal stromal tumors (GIST) have an extremely poor
      prognosis; however, their immunohistochemical and genetic features have not been
      assessed satisfactorily and the mechanisms responsible for their high malignant
      potential remain unclear. We examined the immunohistochemical differences between
      gastric GIST and metastatic lesions in the liver of four patients who had
      undergone a postgastrectomy hepatectomy for metachronous liver metastases. We
      also carried out genetic analysis of the tumors in three of the four cases. In
      all cases, the immunoreactivity profiles, including KIT (CD117), CD34, smooth
      muscle actin (SMA), desmin, S-100 and vimentin, were similar between the gastric
      and metastatic tumors, but the Ki67 labeling index in the metastatic GIST was
      higher than that of the primary GIST. Interestingly, in the case who had received
      neoadjuvant imatinib therapy before gastrectomy, its therapeutic effect was
      observed in most of the primary lesion, with the exception of a specific small
      area with high cellularity. Genetic analysis revealed no acquired mutations in
      the c-kit or PDGFRA genes in the metastatic lesions in any of the patients, but
      loss of heterozygosity (LOH) of the c-kit gene was observed mainly in the
      metastatic tumors in two of the three cases. Furthermore, in the case of
      neoadjuvant imatinib therapy, LOH of the c-kit gene was shown in the high
      cellularity area in the primary lesion and metastatic liver GIST. It is suggested
      that LOH of the c-kit gene is an important event that leads to imatinib
      resistance and metastatic progression of GIST. In conclusion, both gastric and
      metastatic GIST had almost the same immunohistochemical features, except for
      their proliferative activity, and LOH of the c-kit gene played an important role
      in the process of liver metastasis.

PMID- 16441424
TI  - Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with
      risk of lymphoid malignancies.
AB  - It has been speculated that the use of hydroxy-methyl-glutaryl coenzyme A
      reductase inhibitors (statins) is associated with the risk of malignant diseases.
      Considering their immunosuppressive activities, malignant diseases that are
      associated with an immunosuppressive status seem feasible to examine the
      association. We therefore examined the association between statin use and
      development of lymphoid malignancies in a case-control study. Cases were 221
      consecutive incident cases with histopathologically proven lymphoid malignancies
      (lymphoma and myeloma), hospitalized in the Department of Hematology of Toranomon
      Hospital (Tokyo, Japan) between 1995 and 2001. Two independent control groups,
      comprising 442 and 437 inpatients without malignancies from the Departments of
      Orthopedics and Otorhinolaryngology of the same hospital, were selected to test
      for consistency of association. Controls were matched individually with cases for
      age, sex and year of admission. Subject information, including statin use, was
      abstracted from medical records at the time of hospitalization. Strength of
      association was evaluated as an adjusted odds ratios (aOR) using a conditional
      logistic regression model. A higher frequency of statin use was found among
      patients with lymphoid malignancies in comparison with both orthopedic (aOR 2.11,
      95% CI 1.20-3.69, P = 0.009) and otorhinolaryngology patients (aOR 2.59, 95% CI
      1.45-4.65, P = 0.001), the significance being maintained when the two control
      groups were combined (aOR 2.24, 95% CI 1.37-3.66, P = 0.001). In conclusion, we
      observed an elevated risk of lymphoid malignancy with statin use among Japanese
      patients. Further evaluations in different populations are required to draw
      conclusions as to the carcinogenicity of lymphoid malignancies with statin use.

PMID- 16441425
TI  - 1alpha,25-Dihydroxyvitamin D3 downmodulates the functional differentiation of Th1
      cytokine-conditioned bone marrow-derived dendritic cells beneficial for cytotoxic
      T lymphocyte generation.
AB  - Various dendritic cell subsets are induced from bone marrow cells under different
      cytokine conditions. We have demonstrated previously that the Th1-cytokine
      conditioned bone marrow-derived dendritic cell (BMDC) subset BMDC1 (generated in
      the presence of granulocyte-macrophage colony-stimulating factor [GM-CSF] +
      interleukin [IL]-3 + interferon [IFN]-gamma+ IL-12) induces a much stronger type
      1 immune response than BMDC0 (GM-CSF + IL-3). In the present study, we
      investigated the effect of 1alpha,25-dihydroxyvitamine D3 (VitD3), which is a
      known immunomodulating drug, on the differentiation of BMDC subsets. The addition
      of VitD3 significantly influenced the functional differentiation of BMDC1
      compared with BMDC0. Specifically, the addition of VitD3 greatly decreased the
      expression levels of MHC class I, CD80, CD40 and leukocyte function-associated
      antigen (LFA)-1 molecules on BMDC1. In addition, VitD3-treated BMDC1 (VD3-BMDC1)
      almost completely lost their immunostimulating activity for inducing type 1
      immunity and cytotoxic T lymphocyte generation. A failure in the induction of
      type 1 immunity by VD3-BMDC1 appeared to be due to the following: (i) the
      expression of co-stimulatory molecules on VD3-BMDC1 was strongly downmodulated
      compared with BMDC1 generated without VitD3; and (ii) VD3-BMDC1 showed
      significantly lower mRNA expression of IFN-gamma and IFN-beta, factors that are
      essential for cytotoxic T lymphocyte induction. VitD3 inhibited the
      differentiation of functionally competent BMDC1 during the early phase of
      differentiation but not during the late differentiation period. A possible reason
      for the inhibition of BMDC1 differentiation by VitD3 is reduced phosphorylation
      of STAT1 during early differentiation. Taken together, VitD3 strongly suppressed
      T-cell responses by inhibiting functional differentiation of precursor dendritic
      cells into functional BMDC1 that are feasible for inducing Th1-dependent cellular
      immunity.

PMID- 16441426
TI  - Tetramer-blocking assay for defining antigen-specific cytotoxic T lymphocytes
      using peptide-MHC tetramer.
AB  - Peptide-MHC tetramers have been engineered to allow accurate detection of antigen
      specific cytotoxic C lymphocytes (CTL) by flow cytometry. Here, we propose a
      novel use for peptide-MHC tetramers in the specific and sensitive analysis of the
      cytotoxic function of antigen-specific CTL by blocking MHC-restricted antigen
      specific cytotoxicity. We found that pretreatment of ovalbumin (OVA)-specific
      CD8(+) CTL (OT-1 CTL), derived from OT-1 T-cell receptor (TCR)-transgenic mice,
      with OVA(257-264) peptide-H-2K(b) tetramer caused a marked inhibition of the
      cytotoxicity against OVA-expressing EG-7 tumor cells. OVA(257-264) peptide-H
      2K(b) tetramer did not block the cytotoxicity mediated by 2C mouse (H-2(b))
      derived CD8(+) CTL, which recognize allo (H-2L(d)) antigens. Moreover, OT-I CTL
      activity was not inhibited by an irrelevant HBV(208-216) peptide-H-2K(b)
      tetramer. These results indicate that the blocking of CTL activity with peptide
      MHC tetramer was caused by interference with the interaction between the TCR and
      H-2K(b)-OVA(257-264) peptide complex, but not with the CD8-MHC class I
      interaction. The blocking activity of OVA(257-264) peptide-H-2K(b) tetramer was
      reversible because OT-I CTL pretreated with the tetramer recovered their
      cytotoxicity after culturing with interleukin-2 for 24 h. The same results were
      also demonstrated in freshly isolated, in vivo-primed OT-1 CTL sorted by the
      tetramer. These results demonstrate that peptide-MHC tetramer is a useful tool
      for defining MHC-restricted antigen-specific CTL function. Moreover, our finding
      implies that the measurement of CTL activity immediately after tetramer-guided
      sorting is not a suitable method for evaluating the function of in vivo-induced
      tetramer-positive CTL. We believe that the tetramer-blocking assay presented here
      will be useful for functionally monitor the induction of MHC-restricted antigen
      specific CTL during vaccination therapy against tumor and infectious diseases.

PMID- 16441427
TI  - Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin
      alphav-mediated ADAM activity in hepatocellular carcinoma: a novel functional
      target for gefitinib.
AB  - We have shown that the epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor gefitinib ('Iressa', ZD1839) inhibits the development of intrahepatic
      metastases of hepatocellular carcinoma CBO140C12, and EGFR transactivation by
      tumor necrosis factor-alpha is a possible target of gefitinib. In the present
      study, we focused on the fibronectin (FN)-dependent signaling pathway to further
      elucidate the antimetastatic activity of gefitinib in CBO140C12 cells. We
      initially observed that FN induced activation of extracellular signal-regulated
      kinase (ERK), p38 and Akt, as well as cell proliferation and CBO140C12 cell
      invasion. These responses were mediated by EGFR tyrosine kinase, because
      gefitinib inhibited these effects of FN. FN-induced ERK, p38 and Akt activation
      was partly blocked by the Arg-Gly-Asp (RGD)-pseudo-peptide FC-336, anti-alphav
      integrin antibody RMV-7, the broad-spectrum matrix metalloprotease inhibitor
      GM6001 and the broad spectrum a disintegrin and metalloprotease (ADAM) inhibitor
      TAPI-1. But these inhibitors had no effect on EGF-induced signaling pathways,
      suggesting that integrins and ADAM may be upstream components of EGFR in these
      responses. These results suggest that FN-induced activation of ERK, p38, Akt,
      cell proliferation and invasion was mediated, at least in part, via integrins,
      ADAM and EGFR, and that this FN-induced signaling pathway might be involved in
      the antimetastatic activity of gefitinib.

PMID- 16441429
TI  - Intracellular survival of Shigella.
AB  - Bacterial invasion of eukaryotic cells and host recognition and killing of the
      invading bacteria are a key issue in determining the fate of bacterial infection.
      Once inside host cells, pathogenic bacteria often modify the phagosomal
      compartment or enter the host cytosol to escape from the lytic compartment and
      gain a replicative niche. Cytosolic invaders, however, are monitored by host
      innate immune systems, such as mediated by Nod/CARD family proteins, which induce
      inflammatory responses via activation of NF-kappaB. Furthermore, recent studies
      indicate that autophagy, a major cytoplasmic degradation system that eliminates
      cytosolic protein and organelles, also recognizes invading bacteria. Indeed,
      unless they are able to circumvent entrapping by autophagic membranes, bacteria
      targeted by autophagy ultimately undergo degradation by delivery into
      autolysosomes. In this article, we review recent advances in understanding of
      Shigella strategies to infect epithelial cells, and then focus on recent studies
      of an intriguing bacterial survival strategy against autophagic degradation.

PMID- 16441430
TI  - The expanding realm of heterologous immunity: friend or foe?
AB  - Antecedent or current infections can alter the immunopathologic outcome of a
      subsequent unrelated infection. Immunomodulation by co-infecting pathogens has
      been referred to as 'heterologous immunity' and has been postulated to play a
      role in host susceptibility to disease, tolerance to organ transplant, and
      autoimmune disease. The effect of various infections on heterologous immune
      responses has been well studied in the context of shared epitopes and cross
      reactive T cells. It has been shown that prior infections can modulate protective
      immunity and immunopathology by forming a pool of memory T cells that can cross
      react with antigens from heterologous organisms or through the generation of a
      network of regulatory cells and cytokines. While it is not feasible to alter a
      host's history of prior infection, understanding heterologous immune responses in
      the context of simultaneous unrelated infections could have important therapeutic
      implications. Here, we outline key evidence from animal and human studies
      demonstrating the effect of heterologous immunity on the outcome of disease. We
      briefly review the role of T cells, but expand our discussion to explore other
      immune mechanisms that may modulate the response to concurrent active infections.
      In particular, we underscore the role of the innate immune system, polarized
      responses and regulatory mechanisms on heterologous immune responses.

PMID- 16441428
TI  - Epstein-Barr virus involvement is a predictive factor for the resistance to
      chemoradiotherapy of gastric diffuse large B-cell lymphoma.
AB  - Primary gastric diffuse large B-cell lymphomas are generally well controlled by
      non-surgical treatment with combination chemotherapy followed by radiotherapy. We
      have previously reported that over 90% of patients achieved complete response
      (CR) with this therapeutic strategy: three cycles of cyclophosphamide,
      adriamycin, vincristine and prednisone followed by radiotherapy (40.5 Gy).
      Although the CR rate was very high, some patients still showed resistance to this
      combination therapy. In order to clarify the factors related to therapy
      resistance, we examined the relationship between Epstein-Barr virus (EBV), which
      was examined using an in situ hybridization technique, and the patients' clinical
      courses. Out of the 50 patients, four were EBV positive; over half of lymphoma
      cells were positive for EBV by in situ hybridization. Of the three EBV-positive
      patients, two showed progressive disease and one achieved partial response (PR).
      Two of the patients died of disease progression. The other patient achieved CR,
      but the lymphoma recurred with distant metastasis in the cerebellum 3 months
      after remission. In the present study, eight patients did not achieve CR or they
      relapsed, four patients showed progressive disease, one patient achieved PR, and
      three patients achieved CR with recurrence. Therefore, half of these unfavorable
      patients were EBV positive. This finding strongly indicated that EBV-associated
      gastric diffuse large B-cell lymphomas frequently show resistance to standard
      chemoradiotherapy, although some other adverse factors remain unclear.

PMID- 16441431
TI  - Characterization of Brucella abortus lipopolysaccharide macrodomains as mega
      rafts.
AB  - The lipopolysaccharides (LPS) of intracellular Proteobacteria such as Brucella,
      Chlamydia, Legionella and Rickettsia, have properties distinct from
      enterobacterial LPSs. These properties include deficient LPS induction of host
      cell activation, low endotoxicity and resistance to macrophage degradation.
      Together these constitute key virulence mechanisms for intracellular survival and
      replication. We previously demonstrated that B. abortus LPS captured by
      macrophages was recycled back to the plasma membrane where it was found
      associated with macrodomains. Furthermore, this LPS interferes with the MHC class
      II (MHC-II) presentation of peptides to specific T cell hybridomas. Here, we
      characterized the Brucella LPS macrodomains by microscopy and biochemistry
      approaches. We show for the first time that LPS macrodomains act as detergent
      resistant membranes (DRMs), segregating several lipid-raft components, LPS
      binding proteins and MHC-II molecules. Brucella LPS macrodomains remain intact
      for several months in macrophages and are resistant to the disruptive effects of
      methyl beta-cyclodextrin. Fluorescent anisotropy measurements show that B.
      abortus LPS is responsible for the formation of rigid surface membrane complexes.
      In addition, relocalization of MHC-II molecules is observed in these structures.
      The effects of B. abortus LPS on membrane properties could be responsible for
      pathogenic effects such as the inhibition of MHC-II-dependent antigen
      presentation.

PMID- 16441432
TI  - Neutrophil chemotaxis by pathogen-associated molecular patterns--formylated
      peptides are crucial but not the sole neutrophil attractants produced by
      Staphylococcus aureus.
AB  - The chemotactic migration of phagocytes to sites of infection, guided by
      gradients of microbial molecules, plays a key role in the first line of host
      defence. Bacteria are distinguished from eukaryotes by initiation of protein
      synthesis with formyl methionine. Synthetic formylated peptides (FPs) have been
      shown to be chemotactic for phagocytes, leading to the concept of FPs as pathogen
      associated molecular patterns (PAMPs). However, it remains unclear whether FPs
      are major chemoattractants released by bacteria and whether further
      chemoattractants are produced. A Staphylococcus aureus mutant whose
      formyltransferase gene was inactivated (Deltafmt) produced no FPs and the in
      vitro and in vivo ability of Deltafmt culture supernatants to recruit neutrophils
      was considerably reduced compared with those of the parental strain. However,
      some chemotactic activity was retained, indicating that bacteria produce also
      unknown, non-FP chemoattractants. The activity of these novel PAMPs was sensitive
      to pertussis toxin but insensitive to the formyl peptide receptor inhibitor
      CHIPS. Deltafmt culture supernatants caused reduced calcium ion fluxes and
      reduced CD11b upregulation in neutrophils compared with wild-type supernatants.
      These data demonstrate an important role of FPs in innate immunity against
      bacterial infections and indicate that host chemotaxis receptors recognize a
      larger set of bacterial molecules than previously thought.

PMID- 16441433
TI  - Characterization of the tuberculous granuloma in murine and human lungs: cellular
      composition and relative tissue oxygen tension.
AB  - The granulomatous reaction is the hallmark of the host response to infection with
      Mycobacterium tuberculosis. Despite its apparent importance to host defence
      against the tubercle bacillus, the granulomatous response remains to be
      completely defined. The present study used histological, immunohistochemical and
      flow-cytometric analyses to characterize pulmonic granulomatous tissues of
      tuberculous mice and humans. The kinetics of recruitment of neutrophils,
      macrophages, dendritic cells, and T and B lymphocytes into the lungs of mice
      infected aerogenically with the virulent Erdman strain of M. tuberculosis was
      evaluated in detail in both the acute and persistent phase of infection. A
      hypoxia-sensing compound based on the 2-nitroimidazole structure (EF5), together
      with immunohistochemical studies targeting endothelial cells were used to examine
      the relative oxygen tension in tuberculous granulomatous tissues in mice. The
      results have provided evidence that: (i) the granulomatous tissues are a highly
      organized structure whose formation is regulated by orderly recruitment of
      specific immune cells exhibiting distinct spatial relationship with one another;
      (ii) the granulomatous reaction, at least in the mouse, may represent an
      exaggerated response to the tubercle bacillus that can play a role in the
      development of immunopathology; (iii) B lymphoid aggregates are a prominent
      feature in both murine and human granulomatous tissues, although the immune cells
      that are most prominently associated with these clusters vary among the two
      species; (iv) murine tuberculous granulomatous tissues are relatively aerobic,
      suggesting that mouse models of persistent tuberculosis may not be suitable for
      the study of any hypoxic response of M. tuberculosis.

PMID- 16441434
TI  - Abl collaborates with Src family kinases to stimulate actin-based motility of
      vaccinia virus.
AB  - Local activation of Src at the plasma membrane by extracellular vaccinia virus
      results in a signalling cascade that acts to stimulate actin polymerization
      beneath the virus to enhance its cell-to-cell spread. Initiation of this
      signalling cascade involves Src-mediated phosphorylation of tyrosine 112 and 132
      of the viral membrane protein A36R. Here we show that recruitment of Src is
      dependent on its myristoylation and an interaction with A36R upstream of tyrosine
      112 and 132. We further show that Src, Fyn and Yes have unique specificities
      towards these tyrosine residues. Using cell lines deficient in Src, Fyn and Yes,
      we demonstrate that multiple Src family members can stimulate vaccinia-induced
      actin polymerization and also uncover a role for Abl family kinases.
      Additionally, Abl and Arg are able to phosphorylate A36R in vitro and are
      recruited to vaccinia-induced actin tails. The ability of multiple families of
      tyrosine kinases to directly phosphorylate A36R ensures robust cell-to-cell
      spread of vaccinia virus will occur under a variety of cellular conditions.

PMID- 16441435
TI  - Cholesterol depletion in Mycobacterium avium-infected macrophages overcomes the
      block in phagosome maturation and leads to the reversible sequestration of viable
      mycobacteria in phagolysosome-derived autophagic vacuoles.
AB  - Phagocytic entry of mycobacteria into macrophages requires the presence of
      cholesterol in the plasma membrane. This suggests that pathogenic mycobacteria
      may require cholesterol for their subsequent intra-cellular survival in non
      maturing phagosomes. Here we report on the effect of cholesterol depletion on pre
      existing phagosomes in mouse bone marrow-derived macrophages infected with
      Mycobacterium avium. Cholesterol depletion with methyl-beta-cyclodextrin resulted
      in a loosening of the close apposition between the phagosome membrane and the
      mycobacterial surface, followed by fusion with lysosomes. The resulting
      phagolysosomes then autonomously executed autophagy, which did not involve the
      endoplasmic reticulum. After 5 h of depletion, intact mycobacteria had
      accumulated in large auto-phagolysosomes. Autophagy was specific for
      phagolysosomes that contained mycobacteria, as it did not involve latex bead
      containing phagosomes in infected cells. Upon replenishment of cholesterol,
      mycobacteria became increasingly aligned to the lysosomal membrane, from where
      they were individually sequestered in phagosomes with an all-around closely
      apposed phagosome membrane and which no longer fused with lysosomes. These
      observations indicate that, cholesterol depletion (i) resulted in phagosome
      maturation and fusion with lysosomes and (ii) caused mycobacterium-containing
      phagolysosomes to autonomously undergo autophagy. Furthermore, (iii) mycobacteria
      were not killed in auto-phagolysosomes, and (iv) cholesterol replenishment
      enabled mycobacterium to rescue itself from autophagic phagolysosomes to again
      reside individually in phagosomes which no longer fused with lysosomes.

PMID- 16441436
TI  - Integrin-linked kinase is an essential link between integrins and uptake of
      bacterial pathogens by epithelial cells.
AB  - Entry of Streptococcus pyogenes or group A streptococcus (GAS) into host cells is
      mediated by fibronectin bound to surface proteins, M1 or PrtF1, forming a bridge
      to alpha5beta1 integrins. This interaction leads to cytoskeletal rearrangement
      and uptake of streptococci. We postulated that integrin-linked kinase (ILK),
      which directly associates with integrins, is the universal link between integrins
      and several bacterial pathogens. We showed that inhibition of ILK expression by
      siRNA silencing, or ILK kinase activity by chemical inhibitors or expression of a
      dominant negative form of ILK reduced M1-mediated invasion of epithelial cells up
      to 80%. To evaluate the ILK requirement for PrtF1-mediated GAS invasion, a M1
      PrtF1+ recombinant strain within the M1 background was constructed. Inhibition of
      ILK kinase activity also significantly reduced invasion of epithelial cells by
      this recombinant and wild-type strain JRS4 that expresses PrtF1. In addition,
      impaired ILK kinase activity results in significant reduction of integrin
      dependent invasion mediated by invasins of two other important pathogens,
      Staphylococcus aureus and Yersinia spp. This study suggests that bacterial
      pathogens evolved different molecules and strategies to exploit the host integrin
      signalling pathway for their survival.

PMID- 16441437
TI  - Cryptococcus neoformans capsular polysaccharide component galactoxylomannan
      induces apoptosis of human T-cells through activation of caspase-8.
AB  - The major virulence factor of Cryptococcus neoformans is its polysaccharide
      capsule composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM) and
      mannoproteins. A variety of immunomodulating activities have been described for
      GXM and mannoproteins but little is known about possible interactions of GalXM
      with the immune system. In the present article, we investigate the effect of
      purified soluble GalXM on human T lymphocytes. The results indicate that, GalXM
      (i) can affect selected immune responses; (ii) causes significant impairment of T
      cell proliferation and increases interferon-gamma and interleukin-10 production;
      and (iii) induces apoptosis of T lymphocytes through activation of caspase-8 that
      terminates with fragmentation of DNA. These results are the first to suggest a
      role for GalXM in C. neoformans virulence by demonstrating that it can target
      human T cells, and that it may impair the development of an effective specific T
      cell response.

PMID- 16441438
TI  - Infection of bovine cells by the protozoan parasite Theileria annulata modulates
      expression of the ISGylation system.
AB  - The apicomplexan parasite, Theileria annulata, dedifferentiates and induces
      continuous division of infected bovine myeloid cells. Re-expression of
      differentiation markers and a loss of proliferation occur upon treatment with
      buparvaquone, implying that parasite factors actively maintain the altered status
      of the infected cell. The factors that induce this unique transformation event
      have not been identified. However, parasite polypeptides (TashAT family) that are
      located in the infected leucocyte nucleus have been postulated to function as
      modulators of host cell phenotype. In this study differential RNA display and
      proteomic analysis were used to identify altered mRNA and polypeptide expression
      profiles in a bovine macrophage cell line (BoMac) transfected with TashAT2. One
      of the genes identified by differential display was found to encode an ubiquitin
      like protease (bUBP43) belonging to the UBP43 family. The bUBP43 gene and the
      gene encoding its ubiquitin-like substrate, bISG15, were expressed at a low level
      in T. annulata-infected cells. However, infected cells were refractory to
      induction of elevated bISG15 expression by lipopolysaccharide or type 1
      interferons while TashAT2-transfected cells showed no induction when treated with
      camptothecin. Modulation of the ISGylation system may be of relevance to the
      establishment of the transformed infected host cell, as ISGylation is associated
      with resistance to intracellular infection by pathogens, stimulation of the
      immune response and terminal differentiation of leukaemic cells.

PMID- 16441439
TI  - Interleukin-18 secretion and Th1-like cytokine responses in human peripheral
      blood mononuclear cells under the influence of the toll-like receptor-5 ligand
      flagellin.
AB  - Flagellin is the major protein component of the flagella from motile bacteria and
      was identified as the ligand for toll-like receptor (TLR)-5. Whereas its effects
      on epithelial cells have been studied in detail, activation of human peripheral
      blood mononuclear cells (PBMC) by flagellin is characterized only partially. By
      using the recombinant protein of Salmonella muenchen we confirm the
      proinflammatory nature of flagellin as detected by nuclear factor-kappaB
      activation and interleukin (IL)-8 production. Aim of the current study was to
      elucidate in PBMC effects of flagellin on IL-18 and Th1-like cytokine responses.
      We report that flagellin in pathophysiologically relevant concentrations
      augmented release of mature IL-18 by THP-1 monocytes, PBMC, and whole blood
      stimulated with nigericin or by ATP-mediated P2X7 purinergic receptor activation.
      Further key functions of the IL-18/IL-12/interferon-gamma (IFNgamma) pathway were
      upregulated by flagellin. Flagellin synergized with IL-12 for production of IFN
      gamma and augmented secretion of interferon-inducible protein-10, a CXC-chemokine
      that is key to the generation of Th1-type responses. In contrast, neither IL-18
      binding protein nor IL-4 was affected. Taken together, the present data
      demonstrate for the first time that flagellin at concentrations that are
      detectable in the blood compartment during sepsis efficiently enhances the IL
      18/IL-12/IFNgamma pathway and thus Th1-like cytokine responses in PBMC.

PMID- 16441440
TI  - Toxoplasma gondii inhibits ultraviolet light-induced apoptosis through multiple
      interactions with the mitochondrion-dependent programmed cell death pathway.
AB  - Cells infected with the protozoan parasite Toxoplasma gondii are resistant to
      diverse apoptotic stimuli. In this study, we perform a detailed analysis of the
      manipulation of the mitochondrial arm of the apoptotic cascade by the parasite.
      Apoptosis was induced using irradiation with ultraviolet light (UV), and the
      kinetics of caspase activation, cytochrome c release and activation of the
      upstream signalling pathways were examined. The evidence clearly points to T.
      gondii targeting multiple steps in the transmission [inhibition of c-Jun N
      terminal kinase (JNK) activation in response to UV], triggering (inhibition of
      cytochrome c release by affecting the balance of pro- and anti-apoptotic BCL-2
      family members) and execution (inhibition of caspase 9 and caspase 3) phases of
      the apoptotic cascade. Interestingly, the multilevel pattern of inhibition that
      emerges suggests that the global inhibition of the mitochondrial arm of apoptosis
      is not likely to be contributed to by the small subset of mitochondria recruited
      to the T. gondii parasitophorous vacuole membrane.

PMID- 16441441
TI  - Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and
      modulates dendritic cell function.
AB  - Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major
      determinant of dendritic cell (DC) function. Here we report that one of a series
      of meningococcal mutants with defined truncations in the lacto-N-neotetraose
      outer core of the LPS exhibited unique strong adhesion and internalization
      properties towards DC. These properties were mediated by interaction of the
      GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with
      the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin
      receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T
      cell responses driven by DC towards T helper type 1 activity. Thus, the use of
      lgtB LPS may provide a powerful instrument to selectively induce the desired arm
      of the immune response and potentially increase vaccine efficacy.

PMID- 16441442
TI  - ExoS of Pseudomonas aeruginosa induces apoptosis through a Fas receptor/caspase 8
      independent pathway in HeLa cells.
AB  - Pseudomonas aeruginosa infection is a serious complication in immunocompromised
      individuals and in patients with cystic fibrosis. We have previously shown that
      the type III secreted effector ExoS triggers apoptosis in various cultured cell
      lines via its ADP-ribosyltransferase (ADPRT) activity. The apoptosis process was
      further shown to involve intrinsic signalling pathway requiring c-Jun N-terminal
      kinase (JNK)-initiated mitochondrial pathway. In the present study, we
      investigated the role of Fas pathway activation in P. aeruginosa-induced
      apoptosis. P. aeruginosa infection resulted in caspase 8 cleavage in HeLa cells,
      which was inhibited by overexpression of a dominant negative version of Fas
      associated death domain (FADD), suggesting that Fas pathway was activated. In
      fact, confocal laser scanning microscopy showed that P. aeruginosa induced
      clustering of FasR. In addition, the ADPRT activity of the ExoS was required for
      the induction of FasR clustering and caspase 8 cleavage. However, blocking the
      FasR-FasL interaction by antagonistic antibodies to FasR or to FasL had no effect
      on P. aeruginosa-induced caspase 8 and caspase 3 activation, neither did the
      silencing of FasR by small interfering RNA (siRNA), suggesting that caspase 8
      activation through the FADD bypasses FasR/FasL-mediated signalling. Thus, FADD
      mediated caspase 8 activation involves intracellular ExoS in an ADPRT-dependent
      manner. Furthermore, silencing of caspase 8 by siRNA did not interfere with P.
      aeruginosa-induced apoptosis, whereas it rendered HeLa cells markedly increased
      resistance towards FasL-induced apoptosis. In conclusion, our findings indicate
      that ExoS of P. aeruginosa induces apoptosis through a mechanism that is
      independent of Fas receptor/caspase 8 pathway.

PMID- 16441443
TI  - The host cell transcription factor hypoxia-inducible factor 1 is required for
      Toxoplasma gondii growth and survival at physiological oxygen levels.
AB  - Toxoplasma gondii is an obligate intracellular protozoan pathogen. We previously
      found that genes mediating cellular responses to hypoxia were upregulated in
      Toxoplasma -infected cells but not in cells infected with another intracellular
      pathogen, Trypanosoma cruzi. The inducible expression of these genes is
      controlled by the hypoxia-inducible factor 1 (HIF1) transcription factor, which
      is the master regulator of cells exposed to low oxygen. Because this response may
      be important for parasites to grow at physiological oxygen levels, we tested the
      hypothesis that HIF1 is important for Toxoplasma growth. Here, we demonstrate
      that Toxoplasma infection rapidly increased the abundance of the HIF1alpha
      subunit and activated HIF1 reporter gene expression. In addition, we found that
      Toxoplasma growth and survival was severely reduced in HIF1alpha knockout cells
      at 3% oxygen. While HIF1alpha was not required for parasite invasion, we
      determined that HIF1 was required for parasite cell division and organelle
      maintenance at 3% oxygen. These data indicate that Toxoplasma activates HIF1 and
      requires HIF1 for growth and survival at physiologically relevant oxygen levels.

PMID- 16441444
TI  - Phosphorylation, ubiquitination and degradation of listeriolysin O in mammalian
      cells: role of the PEST-like sequence.
AB  - Listeria monocytogenes is a bacterial pathogen that grows within the cytosol of
      infected host cells. Entry into the cytosol is largely mediated by a secreted
      bacterial cytolysin, listeriolysin O (LLO). In order to prevent host cell damage,
      the pore-forming activity of LLO is restricted to the phagosome.
      Compartmentalization of LLO requires a PEST-like sequence; PEST sequences can
      direct eukaryotic proteins for proteasomal degradation. Here we test the
      hypothesis that LLO's PEST-like sequence compartmentalizes pore-forming activity
      by targeting this bacterial protein for degradation in the host cytosol. We show
      that intracellular LLO was degraded in a proteasome-dependent manner, and that,
      prior to degradation, LLO was ubiquitinated and was phosphorylated within the
      PEST-like sequence. However, wild-type LLO and PEST region mutants had similarly
      short intracellular half-lives and both the wild-type and mutant proteins were
      stabilized by inhibitors of host proteasomes. Additionally, blocking host
      proteasomes did not cause toxicity in a wild-type infection, but enhanced the
      cytotoxicity of PEST region mutants. Together with the observation that PEST
      region mutants exhibit higher intracellular LLO levels than wild-type bacteria,
      these data suggest that LLO's PEST-like region does not mediate proteasomal
      degradation by the host, but controls LLO production in the cytosol.

PMID- 16441445
TI  - Ralstonia pickettii-innocent bystander or a potential threat?

PMID- 16441446
TI  - New strategies to identify patients harbouring antibiotic-resistant bacteria at
      hospital admission.
AB  - Nosocomial infections caused by antibiotic-resistant bacteria are associated with
      high morbidity and mortality worldwide. Most prevention strategies focus on cross
      transmission, but the endemic state inside the hospital is also maintained
      through the influx of patients colonised or infected with antibiotic-resistant
      bacteria, balanced by the efflux of colonised patients following discharge.
      Epidemiological research has demonstrated that eradication can be achieved by
      preventing the influx of resistant bacteria. The presence of a central venous
      catheter and a history of methicillin-resistant Staphylococcus aureus (MRSA)
      infection or colonisation are associated significantly with methicillin-resistant
      staphylococcal bacteraemia at admission. Previous antibiotic therapy and transfer
      from long-term care facilities or nursing homes are associated with bacteraemia
      caused by methicillin-resistant coagulase-negative staphylococci, while skin
      ulcer and cellulites are independent risk-factors for MRSA bacteraemia. A scoring
      system using point values has been developed and validated to identify patients
      positive for vancomycin-resistant enterococci at admission. Six variables were
      identified: age > 60 years (2 points); hospitalisation in the previous year (3);
      use of two or more antibiotics during the previous 30 days (3); transfer from
      another hospital or long-term care facility (3); a requirement for chronic
      haemodialysis (2); and a previous history of MRSA infection (4). With a point
      score cut-off of > or = 10, the specificity of this prediction rule is 98%.
      Knowledge of variables identifying patients at high risk for being colonised or
      infected with antibiotic-resistant bacteria may assist clinicians in targeting
      preventive measures and streamlining the use of vancomycin. Current studies are
      analysing risk-factors for harbouring multiresistant Gram-negative bacteria at
      hospital admission.

PMID- 16441447
TI  - gamma-2 Herpes virus post-transcriptional gene regulation.
AB  - gamma-2 herpes viruses, which include Kaposi's sarcoma-associated herpes virus,
      are an important subfamily of herpes virus because of their oncogenic potential.
      Herpes virus saimiri (HVS) is the prototype gamma-2 herpes virus and is a useful
      model to study the basic mechanisms of lytic replication in this subfamily. Like
      all herpes viruses, HVS has two distinct life cycles, latent persistence and
      lytic replication. Analysis of herpes virus genomes has demonstrated that, in
      contrast to cellular genes, most virus genes that are expressed lytically do not
      have introns. Herpes viruses replicate in the nucleus of the host cell, and
      therefore require that the viral intron-lacking mRNAs are exported from the
      nucleus to allow virus mRNA translation. This review focuses upon the role of HVS
      ORF 57, a post-transcriptional regulatory protein, which is conserved in all
      herpes viruses. HVS ORF 57 is a multifunctional protein involved in both trans
      activation and trans-repression of target mRNAs. The major role of the ORF 57
      protein in mediating viral mRNA export is considered, and the ORF 57-host cell
      interactions that are required for this function are discussed.

PMID- 16441448
TI  - Prevalence and persistence of antibodies to herpes viruses, Chlamydia pneumoniae
      and Helicobacter pylori in Alaskan Eskimos: the GOCADAN Study.
AB  - The prevalence and persistence of antibodies against cytomegalovirus (CMV),
      herpes simplex virus types 1 (HSV1) and 2 (HSV2), Helicobacter pylori and
      Chlamydia pneumoniae were determined in Alaskan Eskimos. The study included 610
      individuals (mean age 43 +/- 15 years; 45% males) participating in the Genetics
      of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Archived serum
      samples and those collected during the GOCADAN study were analysed for antibodies
      against the above pathogens by ELISA. The current prevalence of antibody
      seropositivity was 94% to CMV, 90% to HSV1, 38% to HSV2, 80% to H. pylori, and
      42% to C. pneumoniae. The persistence of antibodies (in both archived and current
      samples) against CMV, HSV1 and H. pylori was high (83%, 84% and 67%,
      respectively) compared with those against HSV2 (26%) and C. pneumoniae (29%).
      Moreover, the seroconversion rates to these organisms were low. Most individuals
      acquired CMV, HSV1 and H. pylori antibodies by the age of 24 years (94%, 90% and
      72%, respectively), and >50% carried HSV2 and C. pneumoniae antibodies by the age
      of 45 years. There were gender differences in antibody seropositivity rates. Over
      70% of individuals had antibodies to at least three of the five pathogens tested.
      The study demonstrated the high prevalence and lifelong persistence of multiple
      antibodies, suggesting chronic infections among Alaskan Eskimos.

PMID- 16441449
TI  - Cephalosporinase over-expression resulting from insertion of ISAba1 in
      Acinetobacter baumannii.
AB  - ISAba1-like sequences were identified immediately upstream of the bla(ampC) gene
      in ceftazidime-resistant Acinetobacter baumannii isolates, but were absent in
      ceftazidime-susceptible A. baumannii isolates. AmpC over-expression resulted from
      insertion of ISAba1-like sequences upstream of bla(ampC). ISAba1 provided strong
      promoter sequences, and it was demonstrated that the change in the ribosome
      binding site sequence resulting from insertion of ISAba1 did not influence
      expression of the bla(ampC) gene. Sequence analysis revealed that AmpC sequences
      of A. baumannii isolates were almost identical and that ISAba1 elements had a
      high percentage of identity.

PMID- 16441450
TI  - Real-time PCR targeting a 529-bp repeat element for diagnosis of toxoplasmosis.
AB  - Sensitive and rapid detection of infection with Toxoplasma gondii in transplanted
      immunocompromised patients is crucial for a good prognosis. Two DNA fragments are
      used currently for detecting T. gondii infection by PCR, i.e., the B1 gene and a
      529-bp repeat element that exists in 200-300 copies/genome. This study
      investigated whether targeting the 529-bp repeat element gives better sensitivity
      and accuracy than can be obtained when targeting the B1 gene (35 copies) when
      concentrations of T. gondii DNA are low. The results demonstrated that detection
      of the 529-bp repeat element increased diagnostic sensitivity and accuracy.
      Addition of an internal amplification control did not affect the PCR performance
      and was useful in order to monitor PCR inhibition by non-specific DNA in the
      LightCycler instrument. The real-time PCR was used successfully in a clinical
      context to monitor parasitaemia in the blood of a transplant recipient suffering
      from toxoplasmosis.

PMID- 16441451
TI  - Dynamics of PCR-based diagnosis in patients with invasive meningococcal disease.
AB  - Invasive meningococcal disease continues to be a life-threatening condition and
      rapid diagnosis is important for the administration of appropriate treatment.
      This study focused on the use of PCR for the diagnosis of meningococcal aetiology
      and the dynamics of PCR-based diagnosis over time in various biological samples.
      Sixty cerebrospinal fluid (CSF) and 144 serum samples collected during the first
      week of hospitalisation from 37 patients with laboratory-confirmed invasive
      meningococcal disease were investigated. Overall, 91.9% of CSF samples and 45.9%
      of serum samples were PCR-positive, while culture of CSF and blood was positive
      for only 35% and 39% samples, respectively. Positive PCR results were obtained
      until day 7 with CSF and until day 5 with serum. It is therefore recommended that
      samples for molecular diagnosis should be collected early in the course of
      suspected invasive meningococcal disease.

PMID- 16441452
TI  - Application of four molecular typing methods for analysis of Mycobacterium
      fortuitum group strains causing post-mammaplasty infections.
AB  - A cluster of cases of post-augmentation mammaplasty surgical site infections
      occurred between 2002 and 2004 in Campinas, in the southern region of Brazil.
      Rapidly growing mycobacteria were isolated from samples from 12 patients. Eleven
      isolates were identified as Mycobacterium fortuitum and one as Mycobacterium
      porcinum by PCR-restriction digestion of the hsp65 gene. These 12 isolates, plus
      six additional M. fortuitum isolates from non-related patients, were typed by
      pulsed-field gel electrophoresis (PFGE) and three PCR-based techniques: 16S-23S
      rRNA internal transcribed spacer (ITS) genotyping; randomly amplified polymorphic
      DNA (RAPD) PCR; and enterobacterial repetitive intergenic consensus (ERIC) PCR.
      Four novel M. fortuitum allelic variants were identified by restriction analysis
      of the ITS fragment. One major cluster, comprising six M. fortuitum isolates, and
      a second cluster of two isolates, were identified by the four methods. RAPD-PCR
      and ITS genotyping were less discriminative than ERIC-PCR. ERIC-PCR was
      comparable to PFGE as a valuable complementary tool for investigation of this
      type of outbreak.

PMID- 16441453
TI  - Analysis of mutations in the pbp genes of penicillin-non-susceptible pneumococci
      from Turkey.
AB  - Sequence analysis of the pbp genes from 20 Streptococcus pneumoniae isolates from
      Turkey (eight with high-level penicillin-resistance, nine with low-level
      penicillin-resistance, and three that were penicillin-susceptible) was performed
      and phylogenetic trees were constructed. Most isolates clustered together within
      a single branch that was distinct from sequences deposited previously in GenBank,
      which suggests that these isolates have probably evolved following new
      recombination events. The most prominent active-site mutations, which have also
      been associated previously with resistance, were T371A in PBP1a, E481G followed
      by T451A in PBP2b, and T338A in PBP2x. All isolates also possessed a
      (570)SVES/TK(574) block in the PBP2b sequence, instead of the QLQPT sequence of
      R6, which is fairly uncommon in GenBank sequences. This is the first study to
      analyse alterations in the pbp sequences of pneumococci isolated in Turkey.

PMID- 16441454
TI  - Group A streptococcus bacteraemia: comparison of adults and children in a single
      medical centre.
AB  - Group A streptococcus (GAS) bacteraemia is often associated with soft-tissue
      infection, with significant morbidity and mortality. Little is known concerning
      the differences between adults and children with GAS bacteraemia. Records for 98
      of 116 cases of GAS bacteraemia (60 adults and 38 children, aged 7 days to 96
      years) occurring during a 10-year period (1993-2002) were located and reviewed.
      GAS bacteraemia comprised 0.6% of all bacteraemias in adults, compared to 3.3% in
      children (p < 0.001). The rate of adult GAS bacteraemia was two cases/1000
      hospitalisations, compared to 13/1000 in children (p < 0.001). Seventy-six (78%)
      patients had concomitant tissue involvement, with skin or soft-tissue infection
      being the most common (62%). Fifty-three (88%) of 60 adults and five (13%) of 38
      children had underlying conditions (p < 0.001). Twelve patients died, only one of
      whom was a child. Parameters associated with mortality were older age, lower
      temperature, hypotension, a need for surgical intervention, toxic shock syndrome,
      disseminated intravascular coagulation, thrombocytopenia, lymphopenia,
      hypocalcaemia, renal failure and acidosis (p < 0.05).

PMID- 16441455
TI  - Outbreak of vancomycin-resistant Enterococcus spp. in an Italian general
      intensive care unit.
AB  - Following the identification of two clinical isolates of vancomycin-resistant
      enterococci (VRE) from intensive care unit (ICU) patients, a surveillance
      programme detected that six of eight ICU patients were colonised by VRE. Standard
      epidemic control measures were instituted in the ICU. During a 16-month period,
      13 (2.5%) of 509 ICU patients had VRE-positive swabs upon admission, and 43
      (8.7%) of 496 VRE-negative patients were colonised by VRE in the ICU. Patients
      who acquired VRE in the ICU had a longer ICU stay (p < 0.0001). No other
      statistically significant differences were demonstrated. Two patients had
      documented infection (infection/colonisation index, 3.6%; overall VRE infection
      frequency, 0.4%), but both recovered and were discharged. VRE colonisation did
      not increase the mortality rate. Automated ribotyping identified three clusters
      containing, respectively, the first 52 Enterococcus faecium isolates, two
      Enterococcus faecalis isolates, and two further isolates of E. faecium.
      Multilocus sequence typing demonstrated that two E. faecium isolates
      representative of the two ribotypes belonged to sequence types 78 and 18, and
      that these two isolates belonged to the epidemic lineage C1, which includes
      isolates with a wide circulation in northern Italy. The outbreak was controlled
      by continuous implementation of the infection control programme, and by the
      opening of a new unit with an improved structural design and hand-washing
      facilities.

PMID- 16441456
TI  - Inflammatory response and clinical course of adult patients with nosocomial
      bloodstream infections caused by Candida spp.
AB  - Candida spp. are an important cause of nosocomial bloodstream infection (nBSI)
      and are associated with significant morbidity and mortality. An historical cohort
      study was performed to evaluate the clinical course of 60 randomly selected adult
      patients with nBSIs caused by Candida spp. Patients with BSI caused by Candida
      albicans (n = 38) and non-albicans spp. (n = 22) were compared with 80 patients
      with Staphylococcus aureus BSI by serial systemic inflammatory response syndrome
      (SIRS) and APACHE II scores. The patients had a mean age of 52 years, the length
      of hospital stay before BSI averaged 21 days, and 57% of patients required care
      in an intensive care unit before BSI. The mean APACHE II score was 17 on the day
      of BSI, and 63% of BSIs were caused by C. albicans. Antifungal therapy within the
      first 24 h of onset of BSI was appropriate in 52% of patients. Septic shock
      occurred in 27% of patients, and severe sepsis in an additional 8%. Overall
      mortality was 42%, and the 7-day mortality rate was 27%. The inflammatory
      response and clinical course were similar for patients with BSI caused by C.
      albicans and non-albicans spp. In univariate analysis, progression to septic
      shock was correlated with high overall mortality, as was an APACHE II score >25
      at the onset of BSI. In multivariate analysis, the APACHE II score at the onset
      of BSI and a systemic inflammatory response independently predicted overall
      mortality, but the 7-day mortality rate was only predicted independently by the
      APACHE II score. Clinical course and mortality in patients with Candida BSI were
      predicted by systemic inflammatory response and APACHE II score, but not by the
      infecting species.

PMID- 16441457
TI  - The changing pattern of Fusobacterium infections in humans: recent experience
      with Fusobacterium bacteraemia.
AB  - A retrospective study was conducted of 26 adult cases of fusobacterium
      bacteraemia that occurred between 1998 and 2003 at Center Hospitalier
      Universitaire de Grenoble, France. Most patients presented with pre-existing
      adverse medical conditions, including evolving malignant diseases (eight
      patients), recent surgery (four patients), and chronic organ failure (six
      patients). Only one patient presented with a classic Lemierre's syndrome. These
      results suggest an opportunistic pattern of modern fusobacterium infections.

PMID- 16441458
TI  - Comparison of two fluorescent whiteners, Calcofluor and Blankophor, for the
      detection of fungal elements in clinical specimens in the diagnostic laboratory.
AB  - Fluorescent whiteners, such as Blankophor and Calcofluor white, bind to chitin
      and cellulose, and fluoresce when exposed to UV light. Detection of fungal
      elements from skin and nail samples was faster and more accurate using Blankophor
      compared with potassium hydroxide preparations and Calcofluor (sensitivity and
      specificity 100% and 86% vs. 83-90% and 84-88%, or 80% and 84%, respectively).
      Visibility was improved, and the procedures were simple, inexpensive and rapid,
      all of which are important considerations in a busy diagnostic laboratory.

PMID- 16441459
TI  - Rapid diagnosis of toxinogenic Clostridium difficile in faecal samples with
      internally controlled real-time PCR.
AB  - A real-time PCR assay for Clostridium difficile was developed, based on the tcdB
      gene, which detected all known toxinogenic reference strains (n = 45), within 30
      serogroups and 24 toxinotypes. The analytical sensitivity was 1 x 10(3) CFU/mL,
      and the detection limit in faeces was 1 x 10(5) CFU/g. The optimal protocol for
      DNA extraction from faecal samples involved use of the MagnaPure system with a
      Stool Transport and Recovery (STAR) buffer pre-treatment. In a 1-month
      prospective study of 85 patients with diarrhoea, the sensitivity, specificity and
      positive and negative predictive values of the assay were 100%, 94%, 55% and
      100%, respectively, compared with the standard cell cytotoxicity assay.

PMID- 16441460
TI  - Prevalence of methicillin-resistant Staphylococcus aureus in infected and
      uninfected diabetic foot ulcers.
AB  - This study investigated the prevalence of methicillin-resistant Staphylococcus
      aureus (MRSA) in infected and uninfected diabetic foot ulcers of 84 patients with
      the two types of diabetes. S. aureus was the most common pathogen among the Gram
      positive bacteria isolated from ulcers, and almost 50% of S. aureus isolates were
      MRSA. The prevalence of MRSA was significantly higher in patients with infected
      foot ulcers. MRSA infection or colonisation was not associated with factors
      (previous hospitalisation, use of antibiotics, etc.) known to predispose to MRSA
      colonisation or infection. The high prevalence of MRSA in patients with foot
      ulcers may reflect the increased prevalence of MRSA in the community.

PMID- 16441461
TI  - Molecular characterisation and clonal analysis of group A streptococci causing
      pharyngitis among paediatric patients in Palermo, Italy.
AB  - Group A streptococci (n = 123), isolated consecutively from paediatric patients
      with pharyngitis from Palermo, Italy, were analysed. The emm and sof genes were
      sequenced, the presence of the speA and speC genes was investigated, and the
      macrolide resistance phenotypes and genotypes were determined. A limited number
      of emm/sof genotypes was found, and the most prevalent types were different from
      those found in a previous study from Rome. Macrolide resistance was found in the
      most prevalent clones, suggesting that the spread of mobile antibiotic resistance
      genes among the fittest clones in the community was the main mechanism
      influencing macrolide resistance rates in different emm types.

PMID- 16441462
TI  - Sandfly fever virus outbreak in Cyprus.
AB  - A major outbreak of febrile syndrome occurred during 2002 among the Greek Army
      forces in Cyprus. Serological and molecular investigations revealed that the
      causative agent was a Sicilian-like phlebovirus. A virus strain was isolated from
      a blood sample taken on the first day of the disease. Phylogenetic analysis of
      partial L RNA segment sequences revealed that the strain from Cyprus differed
      from sandfly Sicilian virus by 6.7% at the nucleotide level.

PMID- 16441463
TI  - Antibacterial effects of Eucalyptus globulus leaf extract on pathogenic bacteria
      isolated from specimens of patients with respiratory tract disorders.
AB  - The antibacterial activity of Eucalyptus globulus leaf extract was determined for
      56 isolates of Staphylococcus aureus, 25 isolates of Streptococcus pyogenes, 12
      isolates of Streptococcus pneumoniae and seven isolates of Haemophilus influenzae
      obtained from 200 clinical specimens of patients with respiratory tract
      disorders. MIC50s for these species were 64, 32, 16 and 16 mg/L, respectively;
      MIC90s were 128, 64, 32 and 32 mg/L, respectively; and MBCs were 512, 128, 64 and
      64 mg/L, respectively. These results suggest that further studies to clarify the
      possible therapeutic role of E. globulus leaf extract in the treatment of
      respiratory tract infection are warranted.

PMID- 16441464
TI  - Susceptibility to amoxycillin-clavulanate among clinical isolates of Escherichia
      coli resistant to cefoxitin.

PMID- 16441465
TI  - Review article: Infliximab therapy for inflammatory bowel disease--seven years
      on.
AB  - Infliximab, the chimeric monoclonal IgG1 antibody to tumour necrosis factor, is
      indicated for refractory luminal and fistulizing Crohn's disease and extra
      intestinal manifestations of inflammatory bowel disease. Recently, the active
      ulcerative colitis trials (ACT) studies have shown that infliximab is also
      efficacious to treat ulcerative colitis resistant to standard therapy. Induction
      with 5 mg/kg infliximab at weeks 0, 2 and 6 is advocated. The response to
      infliximab is improved when concomitant immunosuppressive therapy is given. As
      the majority of patients will relapse if not retreated, a long-term strategy is
      necessary. Although episodic therapy can be used, the optimal strategy is
      systematic maintenance treatment with 5 mg/kg intravenous (i.v.) every 8 weeks.
      Long-term maintenance therapy with infliximab results in a reduction of the rate
      of complications, hospitalizations and surgeries associated with Crohn's disease.
      Safety problems with the monoclonal antibody infliximab treatment mainly concern
      the formation of antibodies to infliximab, which may lead to infusion reactions,
      loss of response and serum sickness-like delayed infusion reactions. Latent
      tuberculosis needs to be screened for. The rate of other opportunistic infections
      is slightly increased mainly in patients treated concomitantly with
      immunosuppression. There is no evidence that malignancy rates in patients treated
      with antitumour necrosis factor strategies are increased.

PMID- 16441466
TI  - Systematic review: Complementary and alternative medicine in the irritable bowel
      syndrome.
AB  - BACKGROUND: Complementary and alternative medical therapies and practices are
      widely employed in the treatment of the irritable bowel syndrome. AIM: To review
      the usage of complementary and alternative medicine in the irritable bowel
      syndrome, and to assess critically the basis and evidence for its use. METHODS: A
      systematic review of complementary and alternative medical therapies and
      practices in the irritable bowel syndrome was performed based on literature
      obtained through a Medline search. RESULTS: A wide variety of complementary and
      alternative medical practices and therapies are commonly employed by irritable
      bowel syndrome patients both in conjunction with and in lieu of conventional
      therapies. As many of these therapies have not been subjected to controlled
      clinical trials, some, at least, of their efficacy may reflect the high-placebo
      response rate that is characteristic of irritable bowel syndrome. Of those that
      have been subjected to clinical trials most have involved small poor quality
      studies. There is, however, evidence to support efficacy for hypnotherapy, some
      forms of herbal therapy and certain probiotics in irritable bowel syndrome.
      CONCLUSIONS: Doctors caring for irritable bowel syndrome patients need to
      recognize the near ubiquity of complementary and alternative medical use among
      this population and the basis for its use. All complementary and alternative
      medicine is not the same and some, such as hypnotherapy, forms of herbal therapy,
      specific diets and probiotics, may well have efficacy in irritable bowel
      syndrome. Above all, we need more science and more controlled studies; the
      absence of truly randomized placebo-controlled trials for many of these therapies
      has limited meaningful progress in this area.

PMID- 16441467
TI  - Healing of lymphocytic gastritis after Helicobacter pylori eradication therapy--a
      randomized, double-blind, placebo-controlled multicentre trial.
AB  - BACKGROUND: An association between Helicobacter pylori infection and lymphocytic
      gastritis has been postulated. AIM: To assess the long-term effect of H. pylori
      eradication therapy on lymphocytic gastritis in a double-blind, placebo
      controlled, multicentre trial. METHODS: Patients with lymphocytic gastritis were
      randomized to receive either 1-week triple therapy for eradication of H. pylori
      or omeprazole plus placebo. Endoscopy and histology was performed at baseline and
      after 3 and 12 months. Patients of the omeprazole/placebo group with persistent
      lymphocytic gastritis after 12 months received crossover open-label triple
      therapy. RESULTS: Fifty-one patients were randomized. Intention-to-treat analysis
      revealed a trend to a higher healing rate of lymphocytic gastritis 3 months after
      triple therapy compared with omeprazole/placebo (83.3% vs. 57.7%, 95% CI for RR:
      0.8-2.8, P = 0.06). After 12 months, the healing rate of lymphocytic gastritis
      was significantly higher after triple therapy compared with omeprazole/placebo
      (intention-to-treat 95.8% vs. 53.8%, 95% CI for RR: 1.1-3.5, P = 0.01). All
      patients (n = 5) who received crossover triple therapy, showed healing of
      lymphocytic gastritis after further 12 months. CONCLUSION: Our study demonstrates
      that 1-week triple therapy aiming at eradication of H. pylori leads to a complete
      and long-lasting resolution of lymphocytic gastritis in the majority of patients.

PMID- 16441468
TI  - Efficacy and safety of rifabutin-containing 'rescue therapy' for resistant
      Helicobacter pylori infection.
AB  - BACKGROUND: Current 'rescue' therapies provide inadequate Helicobacter pylori
      eradication rates because of antibiotic resistance. AIM: To test the efficacy of
      a modified triple regimen combining rifabutin, pantoprazole and amoxicillin as
      rescue therapy for patients in whom eradication of H. pylori had failed standard
      clarithromycin-based triple therapy. METHODS: One hundred and thirty patients
      (mean age 51.7 +/- 14.8 years) who had failed one or more eradication attempts
      with omeprazole, clarithromycin and amoxicillin were treated for 12 days with
      rifabutin 150 mg daily, amoxicillin 1 g or 1.5 g t.d.s, and pantoprazole 80 mg
      t.d.s. RESULTS: The intention-to-treat and per-protocol eradication rates were
      90.8/90.8%. Metronidazole or/and clarithromycin resistance had no significant
      impact on H. pylori eradication rates. A higher overall eradication rate of 96.6%
      (95% CI: 92.1-101%) was obtained in patients treated with a regimen containing
      1.5 g amoxicillin t.d.s compared with 90.7% (95% CI: 82-98.6%) using a regimen
      with 1 g amoxicillin t.d.s but the difference was not significant. Side-effects
      reported in 40% of patients were mild. CONCLUSION: A 12-day course of low dose of
      rifabutin with an increased dose of amoxicillin and pantoprazole is well
      tolerated and highly effective against dual-resistant H. pylori infection after
      failure of triple therapy.

PMID- 16441469
TI  - Upper gastrointestinal mucosal abnormalities and blood loss complicating low-dose
      aspirin and antithrombotic therapy.
AB  - BACKGROUND: Little is known about the site and nature of bleeding lesions related
      to low-dose aspirin and other antithrombotic agents. AIM: To describe the mucosal
      abnormalities in patients presenting with upper gastrointestinal bleeding while
      being treated with these drugs. METHODS: The endoscopic findings and clinical
      details were analysed in all patients presenting with haematemesis and/or melaena
      at a single centre during three calendar years. Associations between endoscopic
      findings and risk factors, including the intake of non-steroidal anti
      inflammatory drugs, low-dose aspirin (75 mg daily) and other antithrombotic drugs
      including warfarin, clopidogrel, and dipyridamole, were assessed by logistic
      regression analysis. RESULTS: In 674 upper gastrointestinal bleeders, we found
      that the odds ratio for the presence of erosive oesophagitis in aspirin users was
      2 (95% CI, 1-3; P = 0.03) and 3 (2-5; P = 0.0003) in patients taking other
      antithrombotic agents. In 41 patients with oesophagitis and taking these drugs,
      36 (88%) had cardiovascular disease and only 4 (10%) had peptic symptoms.
      CONCLUSIONS: Erosive oesophagitis is common in patients with upper
      gastrointestinal bleeding taking low-dose aspirin or antithrombotic agents, and
      could potentially be confused with the coexisting heart disease.

PMID- 16441470
TI  - Variants of OCTN1-2 cation transporter genes are associated with both Crohn's
      disease and ulcerative colitis.
AB  - BACKGROUND: Two variants in the organic cation transporter gene cluster have been
      recently reported to confer susceptibility to Crohn's disease (CD). AIM: To
      investigate these variants in CD and ulcerative colitis (UC), and their
      interaction with CARD15 gene and correlation to clinical subphenotypes. METHODS:
      Case-control association analysis was performed in 899 patients (444 CD and 455
      UC) and 611 controls. The organic cation transporter gene cluster single
      nucleotide polymorphisms G207G-->C and 1672C-->T, the IGR2198a_1 single
      nucleotide polymorphism in the IBD5 locus, and the R702W, G908R and L1007finsC
      variants of CARD15 gene were genotyped by ABI-7700, restriction fragment length
      polymorphic analysis and multiplex pyrosequencing, respectively. RESULTS: The
      1672TT and -207CC genotype frequencies were increased in both CD (OR = 1.5, P =
      0.011; OR = 1.6, P = 0.002), and UC (OR = 1.5, P = 0.017; OR = 1.4, P = 0.033),
      respectively. Compared with controls, the TC haplotype frequency was increased in
      both CD (36% vs. 44%, P < or = 0.01) and UC (36% vs. 45%, P < or = 0.01). The
      frequency of the TC haplotype was 43% in CARD15-positive and 44% in CARD15
      negative CD, respectively. Similar results were found in UC. In CD a significant
      association of the TC haplotype was found with presence of perianal fistulae (P =
      0.007) and steno-fistulizing behaviour (P = 0.037). In UC, the TC haplotype was
      more frequent in patients with more extensive disease (P = 0.015), and those on
      immunosuppressives (P = 0.004). CONCLUSIONS: Organic cation transporter gene
      cluster variants may confer susceptibility to both CD and UC, and the TC
      haplotype may influence some clinical features of IBD, but does not interact with
      CARD15 variants.

PMID- 16441471
TI  - Long-term follow-up of chronic hepatitis C patients with sustained virological
      response to various forms of interferon-based anti-viral therapy.
AB  - BACKGROUND: Combination anti-viral therapy achieves a sustained virological
      response (defined as HCV-RNA negativity 6 months after the end of therapy) of 56%
      of patients with chronic hepatitis C. Little is known about long-term durability
      of HCV-RNA negativity in patient treated with pegylated interferon. AIM: To
      evaluate the durability of virologic response in patients with sustained
      virological response to anti-viral therapy treated at our centre. METHODS: A
      total of 187 sustained virological responses (50% genotype 1, 42% genotype 2 or 3
      and 8% genotype 4; 20% with cirrhosis) with a follow-up of >12 months post
      therapy were studied. Twelve patients received monotherapy with interferon
      alpha2a or -2b. One hundred and seventy-five received combination therapy with
      ribavirin and standard interferon-alpha (n = 73) or pegylated interferon-alpha2a
      or 2b (n = 102). Qualitative serum HCV-RNA was tested by COBAS AMPLICOR HCV test,
      v2.0. RESULTS: Median follow-up time was 29 months (range 12-172). Recurrence of
      HCV infection was not observed in any of the 187 sustained virological
      responders. Alanine aminotransferase values were normal in 90% and two patients
      showed minimal elevation of alpha-fetoprotein levels. CONCLUSIONS: No recurrence
      of HCV infection was seen in any patient. Thus, long-term prognosis in chronic
      hepatitis C patients with a sustained virological response to therapy with
      pegylated interferon +/- ribavirin is promising, but long-term studies need to
      continue.

PMID- 16441472
TI  - A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive
      therapies in liver transplantation.
AB  - BACKGROUND: Sirolimus is a potent immunosuppressive agent whose role in liver
      transplantation has not been well-described. AIM: To evaluate the efficacy and
      side-effects of sirolimus-based immunosuppression in liver transplant patients.
      METHODS: Retrospective analysis of 185 patients who underwent orthotopic liver
      transplantation. Patients were divided into three groups: group SA, sirolimus
      alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group
      CNI, calcineurin inhibitors without sirolimus (n = 101). RESULTS: One-year
      patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and
      92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of
      acute cellular rejection at 12 months were comparable among the three groups. At
      the time of transplantation, serum creatinine levels were significantly higher in
      group SA, but mean creatinine among the three groups at 1 month was similar. More
      patients in group SA required dialysis before orthotopic liver transplantation
      (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post
      orthotopic liver transplantation dialysis rates were similar. CONCLUSIONS:
      Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be
      an effective primary immunosuppressant regimen for orthotopic liver
      transplantation patients. Further studies to evaluate the efficacy and side
      effect profile of sirolimus in liver transplant patients are warranted.

PMID- 16441473
TI  - Validation of a 7-point Global Overall Symptom scale to measure the severity of
      dyspepsia symptoms in clinical trials.
AB  - BACKGROUND: Currently there is no consensus on the optimal method to measure the
      severity of dyspepsia symptoms in clinical trials. AIM: To validate the 7-point
      Global Overall Symptom scale. METHODS: The Global Overall Symptom scale uses a 7
      point Likert scale ranging from 1 = no problem to 7 = a very severe problem.
      Validation was performed in two randomized-controlled trials (n = 1121 and 512).
      Construct validity: Global Overall Symptom was compared with the Quality of Life
      in Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease
      Questionnaire and 10 specific symptoms using Spearman correlation coefficients.
      Test-retest reliability: The Intraclass Correlation Coefficient was calculated
      for patients with stable dyspepsia defined by no change in Overall Treatment
      Effect score over two visits. Responsiveness: effect size and standardized
      response mean were also calculated. RESULTS: Construct validity: Change in Global
      Overall Symptom score correlated significantly with Quality of Life for Reflux
      And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease
      Questionnaire and specific symptoms (all P < 0.0002). Reliability: The Intraclass
      Correlation Coefficient was 0.62 (n = 205) and 0.42 (n = 270). Responsiveness:
      There was a positive correlation between change in Global Overall Symptom and
      change in symptom severity. The effect size and standardized response mean were
      1.1 and 2.1, respectively. CONCLUSION: The Global Overall Symptom scale is a
      simple, valid outcome measure for dyspepsia treatment trials.

PMID- 16441474
TI  - Validation of a symptom diary for patients with gastro-oesophageal reflux
      disease.
AB  - BACKGROUND: Symptom diaries are potentially attractive but, because of concerns
      about patient compliance, they have had limited use in clinical trials. We
      assessed the validity and responsiveness of a symptom diary for patients with
      gastro-oesophageal reflux disease. METHODS: We included 215 patients with gastro
      oesophageal reflux disease after starting treatment for 4 weeks with 40 mg
      esomeprazole once daily. Patients recorded whether they experienced night-time
      heartburn (yes/no), the severity of daytime heartburn on a scale from 1 (no
      heartburn) to 4 (severe heartburn) and their antacid use. Patients also completed
      a number of disease-specific and preference-based Health-related Quality of Life
      questionnaires at baseline and follow-up. RESULTS: Consistent with a priori
      predictions, daytime heartburn showed moderate to strong correlations with the
      Quality of Life in Reflux and Dyspepsia questionnaire (0.36-0.67) and four scales
      of symptom severity (0.36-0.70) for baseline, follow-up and change scores, but
      low correlations with the Standard Gamble. Responsiveness of the daytime
      heartburn item was excellent with a mean change from baseline to follow-up of 
      1.3 (95% CI -1.4 to -1.1) and a standardized response mean of 1.33 while
      responsiveness of the daily antacid use item was moderate (mean change scores 
      1.8 tablets taken, 95% CI -2.3 to -1.3 and standardized response mean of 0.64).
      CONCLUSIONS: The excellent psychometric properties of this simple gastro
      oesophageal reflux disease diary make it an attractive measure for future trials.

PMID- 16441475
TI  - A prospective randomized blinded comparison of sodium phosphate and polyethylene
      glycol-electrolyte solution for safe bowel cleansing.
AB  - BACKGROUND: Polyethylene glycol-electrolyte solution (PEG-ELS) is routinely
      prescribed for bowel cleansing. Sodium phosphate (NaP) may be an effective but
      potentially hazardous alternative. AIM: To investigate the safety of prescription
      of either agent, without being informed of the patient's medical history.
      METHODS: One hundred consecutive patients were randomly allocated to PEG-ELS or
      NaP. Prior to and after the bowel cleansing, blood was sampled for renal function
      and electrolytes. Patients answered questionnaires about complaints and ease of
      intake, and endoscopists rated the quality of bowel preparation. RESULTS: Eleven
      patients were identified with a theoretical contraindication for NaP, of whom
      nine should have been discovered by taking a detailed clinical history. Actually,
      six of them received NaP with a doubling of serum phosphate levels or
      hypokalaemia in four. In subjects without a contraindication to the use of NaP,
      hyperphosphataemia developed in 39% and hypocalcaemia in 5%. Patients tolerated
      NaP better and completed the preparation more often. Endoscopists rated the
      quality of bowel preparation equivalent, except for a better cleansed ascending
      colon with PEG-ELS. CONCLUSIONS: The 11% potentially hazardous allocation to NaP
      and the 39% incidence of hyperphosphataemia with NaP do not justify an 'over-the
      counter' prescription. Taking a detailed history and, when in doubt, using PEG
      ELS will safeguard against inappropriate administration of NaP.

PMID- 16441476
TI  - Associations between the IGF system and inflammatory markers in inflammatory
      bowel disease.

PMID- 16441478
TI  - Is oral ciclosporin necessary to switch from i.v. to thiopurines?

PMID- 16441480
TI  - HLA class II disease associations in southern Africa.
AB  - Southern Africa harbors several population groups representing a diversity of
      gene pool origins. This provides a unique opportunity to study genetic disease
      predisposition in these populations against a common environmental background.
      Human leukocyte antigen (HLA) association studies of these populations could
      improve knowledge on inter-population variation and HLA-related disease
      susceptibility. The aim of this paper is to review HLA class II disease
      associations reported for southern African population groups, compare them with
      findings in other populations and identify those unique to southern Africa. A
      number of HLA class II disease associations appear to be unique to southern
      African populations. These include DRB1*14011 association with insulin-dependent
      diabetes mellitus susceptibility in the Xhosa and DRB1*10 and DQB1*0302 with
      rheumatoid arthritis susceptibility in the South African (SA) Indian and SA
      Coloreds, respectively. A noteworthy similarity in class II disease association
      was observed among southern African Caucasoid and their European parental
      populations. Unique HLA class II disease associations observed in southern Africa
      are consistent with the notion that unique environmental and natural selective
      factors have resulted in certain ethnic-specific HLA class II disease
      associations, while common HLA class II disease associations found across
      different populations support the notion that common diseases are caused by
      common, ancient alleles present in indigenous African populations.

PMID- 16441481
TI  - HLA-G levels in serum and plasma.
AB  - HLA-G belongs to the non-classical HLA class-I family of genes presently
      designated as class-Ib genes. There are four membrane-bound (HLA-G1 to -G4) and
      three soluble forms (HLA-G5 to -G7) generated by alternative splicing of the
      primary transcript. HLA-G in the soluble form is found in the plasma, amniotic
      fluid, and cord blood of healthy individuals. Quantitative determination
      suggested that HLA-G levels are genetically controlled. While quantifying soluble
      HLA-G by ELISA, we observed that when plasma and serum levels were measured for
      the same individual, HLA-G plasma values were almost invariably higher than those
      from serum. Our results suggest that HLA-G is trapped and/or consumed during clot
      formation. The amount trapped within the clot is variable and inconsistent. To
      obtain values which reflect the true biological levels, it is therefore
      recommended that HLA-G should be determined in the plasma. If serum levels are
      determined, they should be compared with matched control sera. It should always
      be borne in mind that conclusions concerning sera levels might be erroneous,
      because the true plasma level of the protein can be significantly higher.

PMID- 16441482
TI  - Study of Fas (CD95) and FasL (CD178) polymorphisms in liver transplant
      recipients.
AB  - The Fas receptor is capable of transducing apoptotic cell death upon interaction
      with their ligand (FasL). Recent studies suggest that the Fas/FasL system is
      involved both in graft rejection and in transplantation tolerance. In this study,
      we analyzed the effect of Fas and FasL polymorphisms in liver allograft outcome.
      Fas and FasL polymorphisms were analyzed in 151 primary liver graft recipients.
      The Fas (-670 A/G) and the FasL (IVS2nt -124 A/G and IVS3nt 169 T/delT)
      polymorphisms were analyzed by polymerase chain reaction-restriction fragment
      length polymorphism. Fas -1377 G/A polymorphism was determined by allele-specific
      amplification. Fas and FasL polymorphisms were not associated with acute and
      chronic rejection in liver transplant. In contrast, those recipients bearing the
      AA -670 Fas genotype showed significantly lower graft survival rate (S = 40%)
      than those bearing the GA genotype (S = 63.1%). These differences were detected
      from the first year post-transplant. Multivariate analysis confirmed that the AA
      genotype increased the risk of liver graft loss. This work suggests for the first
      time a possible harmful effect of Fas -670 AA genotype on liver graft survival,
      whereas the Fas and FasL polymorphisms are not associated with acute or chronic
      rejection in liver graft recipients.

PMID- 16441483
TI  - Correlation of interleukin-10 gene haplotype with hepatocellular carcinoma in
      Taiwan.
AB  - Polymorphisms in cytokine genes can influence immune responses, inflammation and
      tissue injury, and may affect the outcome of hepatitis B virus (HBV) infection.
      We analyzed single nucleotide polymorphisms (SNP) in the interleukin (IL)-10 gene
      among 344 HBV carriers and 208 patients with hepatocellular carcinoma (HCC).
      Genotypes and haplotypes were tested for association with HCC. IL-10/-592 C/C
      genotype was associated with a higher risk for HCC compared with IL-10/-592 A/C
      and A/A genotypes [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.2-3.6].
      IL-10/1927 A/A genotype was also associated with a higher risk for HCC compared
      with IL-10/1927 A/C and C/C genotypes (OR: 1.5, 95% CI: 1.0-2.2). Haplotype
      analysis revealed that the homozygosity of the C-A haplotype (defined by SNPs at
      positions -592 and 1927) of IL-10 gene conveys the highest risk for HCC among HBV
      carriers compared with the homozygosity for the A-C haplotype (OR: 2.6, 95% CI:
      1.3-4.9). The results demonstrate that IL-10 gene polymorphism can affect the
      outcome of chronic HBV infection. Further studies are necessary to clarify how
      variation in the IL-10 gene affects IL-10 function and risk of HCC.

PMID- 16441484
TI  - Identification and analysis of MHC class II DRB1 (Patr-DRB1) alleles in
      chimpanzees.
AB  - The MHC-DRB1 gene is known to display the most extensive allelic polymorphisms
      among MHC class II genes. We attempted the selective identification of chimpanzee
      (Pan troglodytes) DRB1 (Patr-DRB1) alleles using the polymerase chain reaction
      (PCR) technique in three steps: first, we performed Patr-DRB1*02 lineage-specific
      8-kb PCR for *02 lineage detection in each chimpanzee; second, we performed 620
      bp PCR for amplification of full-length exon 2; and finally, we carried out an
      insert check using the pattern of microsatellite repeat length variability. In
      the genomic DNA of 23 chimpanzees, nine Patr-DRB1 alleles containing two new
      alleles were detected. Our approach provides a relatively effective method of
      identifying Patr-DRB1 alleles in individual chimpanzees and should also
      contribute to our understanding of the features of MHC molecules in non-human
      primates.

PMID- 16441485
TI  - NFkappaB1 gene does not affect type 1 diabetes predisposition in a Spanish
      population.
AB  - The chromosomal location of the NFkappaB1 gene on 4q, a region linked to type 1
      diabetes (T1D), together with the observed resistance to T1D of NFkappaB1
      deficient mice, suggests its potential role as candidate gene increasing diabetes
      predisposition. Previous association studies in diverse populations yielded
      inconclusive results. Two polymorphisms in the promoter region of the NFkappaB1
      gene have been studied: a functional -94ins/delATTG regulating the gene
      expression and a very informative CA-repeat microsatellite. A strong association
      with the latter was reported in British population but could not be replicated in
      Danish families. No evidence of association was detected for those genetic
      markers in 270 Spanish T1D patients and 484 healthy ethnically matched controls.
      Therefore, it seems that this gene plays no major role in T1D predisposition.

PMID- 16441486
TI  - HLA-A, -B, and -DRB1 polymorphism defined by sequence-based typing of the Han
      population in Northern China.
AB  - DNA typing for human leukocyte antigen (HLA)-A, -B and -DRB1 was performed using
      polymerase chain reaction-sequence-based typing method on 618 randomly selected
      healthy individuals of the Han population in Northern China. Allele frequencies
      and haplotypes were statistically analyzed. A total of 84 HLA-A alleles, 143 B
      alleles, and 122 DRB1 alleles were detected, and 853 A-B-DRB1 haplotypes, 473 A-B
      haplotypes, and 551 B-DRB1 haplotypes were statistically inferred. Statistical
      analysis of three-locus haplotypes showed that A*0207-B*4601-DRB1*0901 (3.06%)
      was the most predominant. Gene frequencies and haplotypic associations within HLA
      A, -B, and -DRB1 loci were determined at a high-resolution (four digit) allelic
      level and should provide useful information in anthropology, bone marrow donor
      registry, legal medicine, and disease association studies.

PMID- 16441487
TI  - Identification of a novel HLA-A allele (A*1115) in the UK National External
      Quality Assessment Schemes for Histocompatibility and Immunogenetics' Educational
      Cell Exchange.
AB  - The novel allele, HLA-A*1115, was identified in an 'Educational Scheme' sample
      (ED03/03 - from a north-western European Caucasoid blood donor) distributed by
      the UK National External Quality Assessment Schemes for Histocompatibility and
      Immunogenetics. ED03/03 was typed by serology, the polymerase chain reaction
      using sequence-specific primers and sequence-based typing. A*1115 is most similar
      to A*110101 with a single mismatch (G to C) at constant position 565, leading to
      a conservative amino acid change from valine (GTG) to leucine (CTG) at codon 165
      in the alpha(2) domain. This substitution has not been reported for any other HLA
      class I allele so far. The HLA-A*1115-bearing haplotype was B*350101; Cw*040101;
      DRB1*140101; DRB3*020201; DQA1*010401; DQB1*0503; DPA1*0103/07; DPB1*030101.
      Extensive serological typing indicated that this allele essentially encodes a
      'normal' HLA-A11 specificity.

PMID- 16441488
TI  - Polymorphism of HLA class II genes in Miao and Yao nationalities of Southwest
      China.
AB  - In the present study, the polymorphism of human leucocyte antigen class II genes
      was investigated by the sequence-based typing method in two Chinese populations:
      the Miaos (n = 85) from Guizhou province and the Yaos (n = 66) from Yunnan
      province. These two populations exhibited certain similarity in their allelic
      distributions. Among 24 DRB1 alleles detected, DRB1*150101, DRB1*140101,
      DRB1*160201 and DRB1*090102 in Miao and DRB1*120201, DRB1*140101, DRB1*150101 and
      DRB1*090102 in Yao were highly predominant. Sixteen DQB1 alleles in total were
      found in these two populations among which DQB1*050201, DQB1*060101/060103 and
      DQB1*030101/0309 in both Miao and Yao and DQB1*050301 in Yao were commonly
      observed. In the 13 DPB1 alleles detected, the most frequent allele was DPB1*0501
      in Miao and Yao followed by DPB1*02 and DPB1*1301. Frequent comparisons with
      other Chinese populations suggested the southern Chinese feature for both the
      Miao and Yao nationalities.

PMID- 16441489
TI  - HLA-DRB1*0826 and HLA-DQB1*0627, two novel class II alleles identified in blood
      stem cell donors of Caucasian origin.
AB  - This report describes two novel HLA class II alleles, HLA-DRB1*0826 and HLA
      DQB1*0627, that have been identified in two unrelated voluntary blood stem cell
      donors of Caucasian origin. HLA-DRB1*0826 is characterized by a nucleotide
      substitution (G to T) in exon 2 at position 163, leading to an amino acid
      exchange from argenine to leucine. The donor phenotype is HLA-A*0301,*2902;
      B*3501,*4403; Cw*0401,*1601; DRB1*0101,*0826; DQB1*0402, *0501. The HLA-DQB1*0627
      alleles contain a nucleotide substitution at position 184 (T to C) resulting in
      an amino acid exchange from tyrosine to histidine. Family segregation analysis
      revealed that the HLA-DQB1*0627 allele belongs to the haplotype A*0101, B*1517,
      Cw*0701, DRB1*1302, DQB1*0627. The donor phenotype is HLA-A*0101; B*0801,*1517;
      Cw*0701; DRB1*1302,*1501; DQB1*0602,*0627.

PMID- 16441491
TI  - HLA-A*2313 is closest to A*2301 but is likely to stimulate T cells when
      mismatched.

PMID- 16441490
TI  - Sequence-based typing reveals a novel DLA-88 allele, DLA-88*04501, in a beagle
      family.
AB  - The dog is an important animal model for solid organ as well as stem cell allo
      transplantation. Methods such as cellular and serological typing and more
      recently sequence-based typing (SBT) have been used to discriminate tissue
      antigen disparity of donor and recipient. We applied SBT for the canine class I
      (DLA-88) and class II (DLA-DRB1) genes in beagle families prior stem cell
      transplantation. A novel DLA-88 (DLA-88*04501) allele in combination with a DLA
      DRB1*01901 allele was found. Sequence comparison of exons 2 and 3 of the novel
      allele revealed most sequence identity to the DLA-88*01301 allele (96.15%
      identity at the nucleotide and 90.65% identity at the protein level).

PMID- 16441492
TI  - Identification of a novel HLA-A*02 allele, A*0287, in the cord blood of a Korean
      baby.

PMID- 16441493
TI  - Identification of a new allele, HLA-A*3308, in the Chinese population.

PMID- 16441494
TI  - A novel HLA-A*680104 variant.

PMID- 16441495
TI  - Identification of two new HLA-A variants, HLA-A*2911 and HLA-A*6827.

PMID- 16441496
TI  - A novel identification of HLA-B*07 allele, HLA-B*0743, in the Korean population.

PMID- 16441497
TI  - Characterization of the novel allele HLA-B*3710.

PMID- 16441498
TI  - Identification of HLA-B*4905 in a Caucasian family.

PMID- 16441499
TI  - HLA-B*1586 is a novel, hybrid HLA-B15/B22 allele with unique serology and
      haplotypic association.

PMID- 16441500
TI  - Identification of two novel HLA-C alleles, HLA-Cw*1217 and HLA-Cw*030404, in
      Singapore Chinese.

PMID- 16441501
TI  - Identification of a novel HLA-DRB1*09 allele, DRB1*0904, in the Korean
      population, by sequence-based typing.

PMID- 16441502
TI  - Identification of a novel HLA-DRB1*11 allele: DRB1*1152.

PMID- 16441503
TI  - Protecting babies: vaccine strategies to prevent foetopathy in Neospora caninum
      infected cattle.
AB  - Neospora caninum is an apicomplexan protozoan parasite that is a significant
      infectious abortifacient agent in cattle. Despite the fact that it is a member of
      a well described taxonomic group, it is a relatively newly discovered parasite
      and its biology is not yet fully understood. Cattle become infected either
      congenitally via transplacental transmission or post-natally by ingesting oocysts
      derived from the definitive host; dogs and coyotes are the only definitive hosts
      that have been described to date. It is not known which of these two forms of
      transmission occurs most frequently and which is the most likely to result in
      abortion; there are no drugs available to treat infected cattle, so current
      control strategies rely on prevention of infection by management methods and
      strict hygiene; an effective vaccine would be a great advantage in its control.
      Neospora caninum is an economically important veterinary pathogen, but we can
      also draw analogies between its foetopathic effects and those of human pathogens
      such as Toxoplasma gondii, Chlamydophila abortus and Plasmodium falciparum.
      Understanding the immune response and the materno-foetal relationship in N.
      caninum-infected cattle may help us to design vaccination strategies, not only
      for neosporosis but also for other foetopathic agents.

PMID- 16441505
TI  - Investigation of recombinant Schistosoma japonicum paramyosin fragments for
      immunogenicity and vaccine efficacy in mice.
AB  - Schistosoma japonicum paramyosin, a 97 kDa myofibrillar protein, is a recognized
      vaccine candidate against schistosomiasis. To improve its expression and to
      identify protective epitopic regions on paramyosin, the published Chinese
      Schistosoma japonicum paramyosin cDNA sequence was redesigned using Pichia codon
      usage and divided into four overlapping fragments (fragments 1, 2, 3, 4) of 747,
      651, 669 and 678 bp, respectively. These gene fragments were synthesized and
      expressed in Pichia pastoris (fragments 2 and 3) or E. coli (fragments 1 and 4).
      The recombinant proteins were produced at high level and purified using a two
      step process involving Ni-NTA affinity chromatography and gel filtration. BALB/c
      mice were immunized subcutaneously three times at 2-week-intervals with the
      purified proteins formulated in adjuvant Quil A. The protein fragments were
      highly immunogenic, inducing high, though variable, ELISA antibody titres, and
      each was shown to resemble native paramyosin in terms of its recognition by the
      anti-fragment antibodies in Western blotting. The immunized mice were subjected
      to cercarial challenge 2 weeks after the final injection and promising protective
      efficacy in terms of significant reductions in worm burdens, worm-pair numbers
      and liver eggs in the vaccinated mice resulted. There was no apparent correlation
      between the antibody titres generated and protective efficacy, as all fragments
      produced effective but similar levels of protection.

PMID- 16441504
TI  - Dissecting Ascaris glycosphingolipids for immunomodulatory moieties--the use of
      synthetic structural glycosphingolipid analogues.
AB  - We have previously shown glycosphingolipids of Ascaris suum to have
      phosphorylcholine (PC) and non-PC immunomodulatory moieties. In the present study
      we further investigated the nature of the immunomodulatory moieties by employing
      three synthetic glycosphingolipids each possessing features of the original
      molecule to examine effects on macrophage and dendritic cell (DC) cytokine
      production and surface co-stimulatory molecule expression. Compound 2, which
      lacked PC but contained ceramide, had no effect on either macrophages or DCs.
      Surprisingly however, Compound 1, which contained PC and hence arguably most
      resembled the native material, had, with the exception of a small increase in
      surface antigen expression, no immunomodulatory properties. Conversely, Compound
      3, which contained PC but was otherwise least like the native molecule,
      demonstrated a number of effects on both macrophages and DCs, including induction
      of Th-1/pro-inflammatory cytokines, inhibition of such cytokines induced by IFN
      gamma/LPS and increased expression of co-stimulatory molecules. Taken together
      these results indicate: (i) that although PC is an immunomodulatory component of
      the native molecule other structural feature are necessary to allow it to act;
      (ii) that carbohydrate rather than ceramide is likely to represent a non-PC
      immunomodulatory moiety; and (iii) that synthetic PC-containing molecules have
      the potential to act as immunomodulatory drugs.

PMID- 16441506
TI  - Genetic variation in resistance to repeated infections with Heligmosomoides
      polygyrus bakeri, in inbred mouse strains selected for the mouse genome project.
AB  - Since the publication of the mouse genome, attention has focused on the strains
      that were selected for sequencing. In this paper we report the results of
      experiments that characterized the response to infection with the murine
      gastrointestinal nematode Heligmosomoides polygyrus of eight new strains (A/J,
      C57BL/6, C3H, DBA/2, BALB/c, NIH, SJL and 129/J), in addition to the well
      characterized CBA (poor responder) and SWR (strong responder) as our controls. We
      employed the repeated infection protocol (consisting of 7 superimposed doses of
      125L3 each administered at weekly intervals, faecal egg counts in weeks 2, 4 and
      6 and assessment of worm burdens in week 6) that was used successfully to
      identify quantitative trait loci for genes involved in resistance to H.
      polygyrus. SWR, SJL and NIH mice performed indistinguishably and are confirmed as
      strong responder strains to H. polygyrus. CBA, C3H and A/J mice all tolerated
      heavy infections and are assessed as poor responders. In contrast, DBA/2, 129/J
      and BALB/c mice performed variably between experiments, some tolerating heavy
      worm burdens comparable to those in poor responders, and some showing evidence of
      resistance, although only in one experiment with female 129/J females and one
      with female BALB/c was the pattern and extent of worm loss much like that in SWR
      mice. Because the genetic relationships between six of the strains exploited in
      this study are now well-understood, our results should enable analysis through
      single nucleotide polymorphisms and thereby provide more insight into the role of
      the genes that control resistance to H. polygyrus.

PMID- 16441507
TI  - Antibodies enhance the protective effect of CD4+ T lymphocytes in SCID mice
      perorally infected with Encephalitozoon cuniculi.
AB  - The role of antibodies in the immune response to microsporidiosis was studied
      using a novel anti-exospore monoclonal antibody (MAb) P5/H1, which recognizes
      surface antigens of Encephalitozoon cuniculi. The effect of the MAb on
      microsporidial infection in vivo was to prolong the survival of previously CD4+
      reconstituted, perorally infected and intraperitoneally MAb-treated SCID mice.
      The MAb decreased the numbers of E. cuniculi spores in peritoneal smears obtained
      post mortem. These results suggest a possible role for antibodies in protection
      against perorally acquired E. cuniculi infection.

PMID- 16441509
TI  - Eosinophil interactions with Haemonchus contortus larvae in the ovine
      gastrointestinal tract.
AB  - Sheep were immunized by weekly oral infections with Haemonchus contortus for 9
      weeks followed by anthelmintic treatment. They were challenged either 9 or 22
      weeks later with PBS (sham controls) or one million exsheathed L3 surgically
      injected in the abomasum, and killed 24 h or 48 h later. Sheep challenged 9 weeks
      after immunization displayed varying degrees of tissue eosinophilia that showed a
      significant inverse relationship with the number of intra-epithelial mast cells
      (globule leucocytes). Close association of eosinophils with tissue larvae was
      observed mainly in the gastric pits (24 h) or on the mucosal surface (48 h). All
      L3-challenged sheep in this group had detectable globule leucocytes and tissue IL
      4 mRNA, as measured by Southern blot RT-PCR. In contrast, sheep challenged 22
      weeks after immunization had no detectable globule leucocytes or IL-4 mRNA and
      although they exhibited consistent tissue eosinophilia, eosinophils were not
      closely associated with tissue larvae. Scanning and transmission electron
      microscopy of sheep sensitized and rested for 9 weeks before challenge showed
      that L3 surrounded by eosinophils were at varying stages of damage and structural
      collapse. These studies strongly indicate that eosinophils can damage and
      probably kill gastrointestinal nematode larvae in vivo. In addition, they also
      suggest that effective killing by tissue eosinophils may depend on other
      microenvironmental factors such as intra-epithelial mast cells and IL-4.

PMID- 16441508
TI  - Evaluation of IFN-gamma production by CD8 T lymphocytes in response to the K1
      peptide from KMP-11 protein in patients infected with Trypanosoma cruzi.
AB  - The cellular response mediated by MHC class I restricted CD8+ T cells has been
      shown to be crucial in the control of Chagas disease. The K1 peptide derived from
      T. cruzi KMP-11 protein has a high binding affinity to the HLA-A*0201 molecule.
      Nevertheless, it is not known whether this peptide is processed and displayed as
      an MHC class I epitope during natural infection by T. cruzi. The aim of this
      study was to evaluate, by ELISPOT assay, the ability of K1 peptide to activate
      CD8+ T lymphocytes to produce IFN-gamma. Therefore, CD8+ T lymphocytes from 22
      HLA-A*0201+ individuals, 12 chronic chagasic patients and 10 uninfected controls,
      were analysed. The results revealed that two of the chagasic patients had IFN
      gamma-secreting CD8+ T cells that were able to respond to K1 peptide with a
      relative frequency of 110 and 230 per million CD8+ T cells. In contrast, none of
      HLA-A*0201+ uninfected controls responded to K1 peptide. Responses to HLA-A*0201
      restricted peptide from the influenza matrix protein were found in six chagasic
      patients and four uninfected controls with an average frequency of 175 and 111
      cells per million CD8+ T cells, respectively. Moreover, a flow cytometric assay
      for degranulation showed that chagasic responders had K1-specific cytotoxic CD8+
      T cells. It is shown here for the first time that the K1 peptide is efficiently
      processed, presented and recognized by CD8+ T lymphocytes during the natural
      course of Chagas disease.

PMID- 16441510
TI  - Microelectrode array studies of basal and potassium-evoked release of L-glutamate
      in the anesthetized rat brain.
AB  - L-glutamate (Glu) is the predominant excitatory neurotransmitter in the mammalian
      central nervous system. It plays major roles in normal neurophysiology and many
      brain disorders by binding to membrane-bound Glu receptors. To overcome the
      spatial and temporal limitations encountered in previous in vivo extracellular
      Glu studies, we employed enzyme-coated microelectrode arrays to measure both
      basal and potassium-evoked release of Glu in the anesthetized rat brain. We also
      addressed the question of signal identity, which is the predominant criticism of
      these recording technologies. In vivo self-referencing recordings demonstrated
      that our Glu signals were both enzyme- and voltage-dependent, supporting the
      identity of L-glutamate. In addition, basal Glu was actively regulated,
      tetrodotoxin (TTX)-dependent, and measured in the low micromolar range
      (approximately 2 microm) using multiple self-referencing subtraction approaches
      for identification of Glu. Moreover, potassium-evoked Glu release exhibited fast
      kinetics that were concentration-dependent and reproducible. These data support
      the hypothesis that Glu release is highly regulated, requiring detection
      technologies that must be very close to the synapse and measure on a second-by
      second basis to best characterize the dynamics of the Glu system.

PMID- 16441511
TI  - Neuronal responses to myelin are mediated by rho kinase.
AB  - CNS myelin inhibits axon growth due to the expression of several growth
      inhibitory proteins, including myelin-associated glycoprotein, oligodendrocyte
      myelin glycoprotein and Nogo. Myelin-associated inhibitory proteins activate rho
      GTPase in responsive neurons. Rho kinase (ROCK) has been implicated as a critical
      rho effector in this pathway due to the ability of the pharmacological inhibitor
      Y-27632 to circumvent myelin-dependent inhibition. Y-27632, however, inhibits the
      activity of additional kinases. Using three independent approaches, we provide
      direct evidence that ROCKII is activated in response to the myelin-associated
      inhibitor Nogo. We demonstrate that Nogo treatment enhances ROCKII translocation
      to the cellular membrane in PC12 cells and enhances ROCKII kinase activity
      towards an in vitro substrate. In addition, Nogo treatment enhances
      phosphorylation of myosin light chain II, a known ROCK substrate. Further, we
      demonstrate that primary dorsal root ganglia neurons can be rendered insensitive
      to the inhibitory effects of myelin via infection with dominant negative ROCK.
      Together these data provide direct evidence for a rho-ROCK-myosin light chain-II
      signaling cascade in response to myelin-associated inhibitors.

PMID- 16441512
TI  - Homocysteine-induced endoplasmic reticulum protein (Herp) is up-regulated in
      sporadic inclusion-body myositis and in endoplasmic reticulum stress-induced
      cultured human muscle fibers.
AB  - Herp is a stress-response protein localized in the endoplasmic reticulum (ER)
      membrane. Herp was proposed to improve ER-folding, decrease ER protein load, and
      participate in ER-associated degradation (ERAD). Intra-muscle-fiber ubiquitinated
      multiprotein-aggregates containing, among other proteins, either amyloid-beta
      (Abeta) or phosphorylated tau are characteristic of sporadic inclusion-body
      myositis (s-IBM). ER stress and proteasome inhibition appear to play a role in s
      IBM pathogenesis. We have now studied Herp in s-IBM muscle fibers and in ER
      stress-induced or proteasome-inhibited cultured human muscle fibers. In s-IBM
      muscle fibers: (i) Herp was strongly immunoreactive in the form of aggregates,
      which co-localized with Abeta, GRP78, and beta2 proteasome subunit; (ii) Herp
      mRNA and protein were increased. In ER-stress-induced cultured human muscle
      fibers: (i) Herp immunoreactivity was diffusely increased; (ii) Herp mRNA and
      protein were increased. In proteasome-inhibited cultured human muscle fibers: (i)
      Herp immunoreactivity was in the form of aggregates; (ii) Herp protein was
      increased, but its mRNA was not. Accordingly, in s-IBM muscle fibers: (i)
      increase of Herp might be due to both ER-stress and proteasome inhibition; (ii)
      co-localization of Herp with Abeta, proteasome, and ER-chaperone GRP78 could
      reflect its possible role in processing and degradation of cytotoxic proteins in
      ER.

PMID- 16441513
TI  - Reversion of the biochemical defects in murine embryonic Sandhoff neurons using a
      bicistronic lentiviral vector encoding hexosaminidase alpha and beta.
AB  - Sandhoff disease, a neurodegenerative disorder characterized by the intracellular
      accumulation of GM2 ganglioside, is caused by mutations in the hexosaminidase
      beta-chain gene resulting in a hexosaminidase A (alphabeta) and B (betabeta)
      deficiency. A bicistronic lentiviral vector encoding both the hexosaminidase
      alpha and beta chains (SIV.ASB) has previously been shown to correct the beta
      hexosaminidase deficiency and to reduce GM2 levels both in transduced and cross
      corrected human Sandhoff fibroblasts. Recent advances in determining the
      neuropathophysiological mechanisms in Sandhoff disease have shown a mechanistic
      link between GM2 accumulation, neuronal cell death, reduction of
      sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) activity, and axonal
      outgrowth. To examine the ability of the SIV.ASB vector to reverse these
      pathophysiological events, hippocampal neurons from embryonic Sandhoff mice were
      transduced with the lentivector. Normal axonal growth rates were restored, as was
      the rate of Ca(2+) uptake via the SERCA and the sensitivity of the neurons to
      thapsigargin-induced cell death, concomitant with a decrease in GM2 and GA2
      levels. Thus, we have demonstrated that the bicistronic vector can reverse the
      biochemical defects and down-stream consequences in Sandhoff neurons, reinforcing
      its potential for Sandhoff disease in vivo gene therapy.

PMID- 16441514
TI  - The positive allosteric modulator GS39783 enhances GABA(B) receptor-mediated
      inhibition of cyclic AMP formation in rat striatum in vivo.
AB  - We studied the effects of the positive allosteric modulator GS39783 on GABA(B)
      receptors at a biochemical level in vivo. Changes in extracellular levels of
      cyclic AMP following GABA(B) receptor activation were monitored in the striatum
      of freely moving rats using microdialysis. Locally applied GABA(B) agonist R(-)
      baclofen inhibited cyclic AMP formation stimulated by a water-soluble forskolin
      analogue in a concentration-dependent manner (EC50 7.3 microM, maximal inhibition
      40%). The selective GABA(B) antagonist CGP56999 reversed R(-)-baclofen-induced
      cyclic AMP inhibition to control levels, but not higher. Orally applied GS39783
      lacked effects on its own but, together with a threshold concentration of R(-)
      baclofen (1 microM), significantly decreased cyclic AMP formation in a dose
      dependent fashion. Effects of GS39783 were revoked with CGP56999, showing
      dependence on GABA(B) receptor activation and suggesting allosteric modulation as
      a mechanism of action in vivo. Administered with a maximally active dose of R(-)
      baclofen, GS39783 failed to further inhibit cyclic AMP formation. The data
      obtained with CGP56999 and the lack of effect of GS39783 alone suggest that there
      is no detectable endogenous activation of GABA(B) receptors controlling cyclic
      AMP formation in rat striatum. To our knowledge, these results provide the first
      biochemical demonstration of in vivo activity of a G protein-coupled receptor
      positive allosteric modulator.

PMID- 16441515
TI  - Nucleic acid binding agents exert local toxic effects on neurites via a non
      nuclear mechanism.
AB  - The mechanism by which drugs that target nucleic acids cause neurotoxicity is not
      well described. We characterized the neurotoxicity of Hoechst 33342 (bis
      benzimide), a common cell permeable nuclear dye, in primary neuronal cultures.
      The mechanism of cell death was not apoptotic, as death is rapid, not accompanied
      by typical nuclear morphological changes, and is insensitive to inhibitors of
      transcription, translation and caspase activity. In addition, free-radical
      scavenging agents failed to attenuate cell death, and damage was not accompanied
      by mitochondrial dysfunction. Neuronal processes of cells exposed to Hoechst
      33342 display dramatic fragmentation prior to cell death. When this compound was
      applied selectively to the distal axons of sympathetic neurons grown in
      compartmented cultures, the distal axons were destroyed. However, the proximal
      processes present in the cell body compartment were spared, demonstrating direct
      axonal toxicity rather than a remote effect of nuclear dysfunction. Other cell
      permeable nucleic acid binding dyes similarly caused rapid dendritic and axonal
      toxicity. The hypothesis that these nucleic acid binding dyes target RNA
      localized to dendrites and axons is supported by observations that RNaseV1
      induced similar, rapid neurite fragmentation. We conclude that the neurotoxic
      effects of nucleic acid binding compounds are mediated, at least in part, by
      direct neurite injury, which does not require involvement of the cell body and
      nucleus.

PMID- 16441517
TI  - Endogenous GD3 ganglioside induces apoptosis in U-1242 MG glioma cells.
AB  - GD3 ganglioside induces apoptosis in several cell types, but the molecular events
      through which this occurs are largely unknown. We investigated the apoptotic
      effects of GD3 expression using U-1242 MG glioblastoma cells, as these cells
      synthesize almost exclusively GM3 and GM2 but not GD3. To express GD3 under the
      control of the TetOn system with minimum leakage, we modified the system by
      constructing a single tri-cistronic retrovirus vector containing three genes
      separated by two internal ribosome entry sites: (a) transcriptional silencer,
      tTS; (b) mutant of reverse transcriptional activator, rtTA2(S)-M2 (provided by H.
      Bujard, Heidelberg, Germany); and (c) enhanced green fluorescent protein (EGFP),
      as an indicator of the tri-cistronic gene expression. Using flow cytometry, we
      selected glioma cells (U1242MG-GD3 clone) that express high levels of GD3 in
      response to doxycycline. Expression of GD3 was associated with apoptosis as
      verified by annexin-V binding, TdT-mediated dUTPnick end-labelling assay (TUNEL),
      and EGFP degradation. GD3-induced apoptosis occurred via caspase-8 activation, as
      GD3 caused cleavage of caspase-8 and inhibition of caspase-8 activation by zlETD
      fmk minimized GD3-induced apoptosis.

PMID- 16441518
TI  - Direct mass spectrometric peptide profiling and fragmentation of larval peptide
      hormone release sites in Drosophila melanogaster reveals tagma-specific peptide
      expression and differential processing.
AB  - Regulatory peptides represent a diverse group of messenger molecules. In insects,
      they are produced by endocrine cells as well as secretory neurones within the
      CNS. Many regulatory peptides are released as hormones into the haemolymph to
      regulate, for example, diuresis, heartbeat or ecdysis behaviour. Hormonal release
      of neuropeptides takes place at specialized organs, so-called neurohaemal organs.
      We have performed a mass spectrometric characterization of the peptide complement
      of the main neurohaemal organs and endocrine cells of the Drosophila melanogaster
      larva to gain insight into the hormonal communication possibilities of the fruit
      fly. Using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF)
      and MALDI-TOF-TOF tandem mass spectrometry, we detected 23 different peptides of
      which five were unpredicted by previous genome screenings. We also found a
      hitherto unknown peptide product of the capa gene in the ring gland and
      transverse nerves, suggesting that it might be released as hormone. Our results
      show that the peptidome of the neurohaemal organs is tagma-specific and does not
      change during metamorphosis. We also provide evidence for the first case of
      differential prohormone processing in Drosophila.

PMID- 16441516
TI  - Mapping superoxide dismutase 1 domains of non-native interaction: roles of intra-
      and intermolecular disulfide bonding in aggregation.
AB  - Superoxide dismutase 1 (SOD1) proteins harboring mutations linked to familial
      amyotrophic lateral sclerosis (FALS) uniformly show heightened potential to form
      high molecular weight structures. Here, we examine the domains of SOD1 that are
      involved in forming these structures (aggregates) and study the role of intra-
      and intermolecular disulfide bonds. An analysis of disease mutations identified
      to date reveals a non-random distribution with predominant occurrence at residues
      within highly conserved beta-strands or at highly conserved residues in loop
      domains. Using a cell transfection assay for aggregation, we determined that no
      single domain in SOD1 is indispensable in the formation of sedimentable
      aggregates, suggesting multiple potential motifs in the protein mediate non
      native interactions. By a cell-free aggregation assay, analysis of transgenic
      mouse tissues, and mutagenesis approaches, we found evidence that redox
      conditions may modulate SOD1 aggregation; reduction of the native intramolecular
      disulfide bonds may predispose SOD1 to unfolding and aggregation, whereas non
      native intermolecular disulfide linkages may help stabilize aggregates in vivo.
      The results suggest a possible mechanism for diversity in the structures formed
      by different SOD1 mutants, and define a potential contribution of redox
      conditions to SOD1 aggregation.

PMID- 16441519
TI  - Systematic screening for Chlamydia trachomatis: estimating cost-effectiveness
      using dynamic modeling and Dutch data.
AB  - OBJECTIVE: To estimate the cost-effectiveness of a systematic one-off Chlamydia
      trachomatis (CT) screening program including partner treatment for Dutch young
      adults. METHODS: Data on infection prevalence, participation rates, and sexual
      behavior were obtained from a large pilot study conducted in The Netherlands.
      Opposite to almost all previous economic evaluations of CT screening, we
      developed a dynamic Susceptible-Infected-Susceptible (SIS) model to estimate the
      impact of the screening program on the incidence and prevalence of CT in the
      population. SIS models are widely used in epidemiology of infectious diseases,
      for modeling the transmission dynamics over time. Subsequently, a predictive
      decision model was used to calculate the complications averted by the screening
      program. Cost-effectiveness was expressed as the net costs per major outcome
      averted (MOA) and was estimated in the baseline analysis and in sensitivity
      analysis. RESULTS: The overall prevalence decreased from 1.79% to 1.05% as a
      result of the screening program directed at both men and women. The program costs
      were mainly offset by the averted costs, although not fully. Resulting net costs
      per MOA were 373 euro sin the baseline analysis. Sensitivity analysis showed that
      partner treatment and sending a reminder are important aspects improving cost
      effectiveness. Additionally, restricting the screening to women only was
      estimated to save costs. CONCLUSIONS: Our cost-effectiveness analysis shows that
      the Dutch society has net to pay for the prevention of CT-complications through
      screening young men and women. One could argue although that 373 euros per MOA
      presents a reasonable cost. A screening program consisting of screening women
      only should always be adopted from a pharmacoeconomic point of view. Our dynamic
      approach appreciates better the specific characteristics of an infectious
      disease, such as CT.

PMID- 16441520
TI  - Economic evaluation of voriconazole versus conventional amphotericin B in the
      treatment of invasive aspergillosis in Germany.
AB  - OBJECTIVE: To assess the costs and cost-effectiveness of voriconazole in
      comparison to conventional amphotericin B (CAB) for the treatment of invasive
      aspergillosis in Germany. METHODS: The cost-effectiveness of voriconazole in
      comparison to CAB was evaluated with a lifetime Markov model, focusing on the
      long-term survival of patients treated for invasive aspergillosis. Long-term
      survival was extrapolated from survival after 12 weeks of treatment, obtained
      from a randomized aspergillosis study. Information on medical resource
      consumption and treatment pathways were obtained from this study and an expert
      committee. With probabilistic analysis the cost-effectiveness of voriconazole
      compared with amphotericin B was analyzed and expressed in incremental costs per
      life-weeks gained. The evaluation was performed from a limited societal
      perspective (both inpatient and outpatient costs) and hospital perspective (only
      inpatient costs). RESULTS: Average survival of patients treated with voriconazole
      was 174.4 life-weeks (95% confidence interval [CI] 159.4-191.3), compared with
      119.4 life-weeks (95% CI 106.4-132.3) for amphotericin B. With voriconazole, the
      mean total costs per patient were 30,026 euros (95% CI 23 euros ,118-37,947)
      compared with 26,669 euros for amphotericin B (95% CI 21,259-34,263 euros ) from
      the limited societal perspective. The corresponding incremental cost
      effectiveness ratio was 62 euros per life-week gained (i.e., 3224 euros per life
      year gained). Hospital costs were approximately 90% of the mean total costs.
      CONCLUSIONS: In the treatment of invasive aspergillosis, voriconazole is cost
      effective in comparison to amphotericin B. Hospital costs are comparable for both
      treatments and are expected to be reimbursed based on the German diagnosis
      related groups (DRG) system 2005.

PMID- 16441521
TI  - The new injury severity score: better prediction of functional recovery after
      musculoskeletal injury.
AB  - OBJECTIVES: Injury Severity Score (ISS) is the most widely used method of
      assessing severity of injury in blunt trauma. It has been recognized that, by
      only allowing the score to consider the worst injury for each body system, ISS
      underestimates the problems of multiple musculoskeletal injuries. The New ISS
      (NISS) allows the three most severe injuries to be scored, irrespective of region
      affected, and may give better prediction of functional recovery in these
      patients. METHODS: A prospective cohort study of 200 patients with
      musculoskeletal injuries, examining the predictive value of ISS and NISS on
      functional recovery as measured by patient-derived outcome measures (Short Form
      36, Sickness Impact Profile, and Musculoskeletal Function Assessment). RESULTS:
      NISS was greater than ISS in 34 patients (17%). NISS showed closer correlation
      with total scores and subscores of the outcomes measures than did ISS (Spearman's
      rho ranked test, P < 0.05). CONCLUSIONS: NISS, a simple modification from ISS,
      better predicts functional outcomes in survivors of musculoskeletal trauma, and
      offers an improvement in the assessment of effectiveness of trauma care delivery.

PMID- 16441522
TI  - Pramipexole versus levodopa in patients with early Parkinson's disease: effect on
      generic and disease-specific quality of life.
AB  - OBJECTIVE: Although health-related quality of life (HRQOL) has been included in
      multiple Parkinson's disease (PD) clinical trials, little is known about how
      HRQOL responds to treatments over time. Here we assess the effect of therapy on
      HRQOL and explore factors that influence the HRQOL profiles and subdomains.
      METHOD: A total of 301 subjects with early PD were randomized to either initial
      pramipexole or initial levodopa and followed every 3 months over a 4-year period.
      To estimate health outcomes, we used EQ-5D and PDQUALIF. We calculated the
      incremental effectiveness as the accumulated difference in the total HRQOL over
      time between treatments. The subgroup analyses (by sex, race, age, baseline
      patient characteristics, and occurrence of adverse events) were conducted using
      the same approach. Sensitivity analysis was performed to test the effect of
      missing data imputation on the results. RESULTS: All three HRQOL measures
      resulted in similar profiles over time characterized by initial improvement over
      the first 3 to 6 months and followed by a gradual decline in years 2, 3, and 4.
      The difference in HRQOL between the treatment arms widened in favor of
      pramipexole in years 3 and 4 for all HRQOL measures used (EQ-5D: Y3 0.048, P =
      0.03; Y4 0.071, P = 0.04). Our analyses suggested that the effect of pramipexole
      on HRQOL was mediated through nonmotor functions, whereas levodopa improved
      primarily motor domains of HRQOL. CONCLUSION: Our results suggest that
      pramipexole and levodopa affect patient HRQOL via improvement on different
      domains of well-being: nonmotor effect for pramipexole and mobility improvement
      for levodopa.

PMID- 16441523
TI  - Discrepancies between patient-reported outcomes and clinician-reported outcomes
      in chronic venous disease, irritable bowel syndrome, and peripheral arterial
      occlusive disease.
AB  - OBJECTIVE: To explore the degree of agreement between patient- and clinician
      reported outcomes (PROs and CROs, respectively) in three chronic diseases.
      METHODS: Respectively, 120, 131, and 61 French general practitioners (GPs)
      included 291, 307, and 90 patients with chronic venous disease (CVD), irritable
      bowel syndrome (IBS), and peripheral arterial occlusive disease (PAOD), in a
      cross-sectional survey. Patients completed a specific Health-Related Quality of
      Life (QoL) questionnaire (Chronic Venous Insufficiency Questionnaire [CIVIQ],
      Functional Digestive Disorders Quality of Life [FDDQL], and Claudication Scale
      [CLAU-S], respectively) and scored their pain (visual analog scale, pain-free
      walking distance). GPs were concomitantly asked to estimate patients' pain and
      QoL. RESULTS: Although correlated (CVD and IBS: Kw = 0.27 and Kw = 0.31,
      respectively; PAOD: r = 0.64, P < 0.01), pain intensity estimated by GPs was
      lower than as estimated by patients with CVD and IBS (e.g., 39.0 +/- 24.9 vs.
      30.4 +/- 21.0 for IBS), and pain-free walking distance was greater as estimated
      by GPs than by patients with PAOD. Pain estimated by patients only partially
      reflected their QoL (r between 0.30 and 0.78; P between 0.02 and <0.01). Global
      QoL scores estimated by patients and GPs were moderately correlated (Kw between
      0.17 and 0.28). GPs underestimated QoL impairment in CVD (global score: 72 +/- 19
      vs. 61 +/- 20) and in most dimensions of the IBS questionnaire (in six of eight
      dimensions), and overestimated QoL impairment in PAOD (54 +/- 21 vs. 66 +/- 23).
      CONCLUSIONS: Although correlated, PROs and CROs differed. In addition, their
      relationship was not consistent across diseases. PROs are therefore essential to
      take account of all the aspects of diseases.

PMID- 16441524
TI  - Measurement of HRQL using EQ-5D in patients with type 2 diabetes mellitus in
      Japan.
AB  - OBJECTIVES: We measured the health-related quality of life (HRQL) of diabetes
      mellitus patients using the Japanese version of EQ-5D, and examined the
      relationship between clinical condition and health status. METHODS: A study was
      conducted on 220 patients with type 2 diabetes mellitus at a hospital in Saitama
      Prefecture on the day of their visit from November 17 to December 24, 1998.
      Patients evaluated their health status using five dimensions (5D) and a visual
      analog scale (VAS). The EQ-5D score was calculated based on the 5D responses
      using the Japanese version of the value set. RESULTS: There were no responses of
      "extreme problem." The frequency of "some problem" was significantly higher in
      patients with complications than in those without for mobility (27.4% and 14.4%)
      and anxiety/depression (25.7% and 13.5%). The mean EQ-5D score was 0.846 (95%
      confidence interval [CI] 0.817-0.874) in patients with complications versus 0.884
      (95% CI 0.855-0.914) in those without complications. There was no statistically
      significant difference between VAS scores according to the presence or absence of
      diabetic complications, but a significant difference in VAS scores was seen
      according to the presence or absence of retinopathy. CONCLUSION: These findings
      suggest the value of measuring health status in diabetes mellitus patients,
      because it is able to comprehensively evaluate the patient's health condition,
      and add another dimension to the subjective symptoms and laboratory data.

PMID- 16441525
TI  - Developing better economic models of osteoporosis: considerations for the
      calculation of the relative risk of fracture.
AB  - OBJECTIVE: Simulation models are often used to assess cost-effectiveness of
      osteoporosis therapies. Many cost-effectiveness analyses are interested in a
      subset of the general population, such as high-risk patients. As the analyses are
      very sensitive to the assumed risk of fracture, it is imperative that the rates
      accurately reflect the fracture risk in the specified target population. The
      objective of this study was to describe the methodological difficulties and
      present some possible solutions for calculating the risk of fracture in target
      populations of interest. METHODS: For binary risk factors, a method for
      converting from a relative risk (RR) for people with a risk factor relative to
      those without, to an RR in the target population compared with the general
      population, is described. For continuous risk factors (i.e., bone mineral density
      [BMD]), data are often provided as an RR of fracture per SD decrease. A method
      for converting from an RR per SD decrease to an RR in those below a certain BMD
      threshold, compared with the general population, is presented. RESULTS: These
      results should allow future economic models to more accurately incorporate
      existing knowledge of risk factors by introducing methods to calculate fracture
      risk estimates in a target population. CONCLUSION: It illustrates the importance
      of considering the prevalence of risk factors in the general population when
      calculating RR in a target population.

PMID- 16441526
TI  - A comparison of depressive symptoms in stroke and primary care: applying Rasch
      models to evaluate the center for epidemiologic studies-depression scale.
AB  - OBJECTIVES: Clinical trials and community-based studies often include the Center
      for Epidemiologic Studies-Depression scale (CES-D) as a measure of depression
      outcome. We compared responses to symptom-related items on the CES-D by depressed
      stroke and primary-care patients for several purposes: 1) to illustrate the use
      of Item Response Theory (IRT)-based (Rasch) models for comparing scale
      functioning across different patient subgroups; and 2) to inform clinicians and
      outcome researchers about scale functioning and depressive symptomatology in
      stroke- compared with primary care-based depression. METHODS: Two data sources
      were analyzed, including 32 depressed patients who were 3 months poststroke, and
      366 depressed primary-care patients. Presence of depression was based on a CES-D
      score 16 or higher. Rasch models were used to assess item fit and compare item
      hierarchies between depressed primary-care and stroke patients. RESULTS: Item
      hierarchies were similar for poststroke depression and primary care-based
      depression. Interpersonal disruption items were the most difficult to endorse for
      both groups. No items misfit the scale in primary-care depression. Items relating
      to restless sleep, unfriendliness, and crying slightly misfit the scale in stroke
      patients, that is, may measure a different trait. Differential item functioning
      (DIF) between the groups was identified for items relating to appetite, restless
      sleep, crying, and feeling disliked. CONCLUSIONS: Results generally supported the
      use of the CES-D as measure of depression outcome, particularly in primary care
      based depression. DIF may imply that slightly different clusters of depressive
      symptoms are reported by depressed stroke patients compared with primary care,
      but this is conjectural given the small stroke sample size and the same items
      have been previously associated with bias in studies of large nonstroke samples.
      This study found Rasch models to be useful tools to investigate scale performance
      for different clinical applications.

PMID- 16441531
TI  - Prehospital care pathway delays: gender and myocardial infarction.
AB  - AIM: This paper reports the findings of a study that identified gender specific
      prehospital care pathway delays amongst Irish women and men with myocardial
      infarction. BACKGROUND: Women are more likely to experience a poorer prognosis
      than their male counterparts following hospitalization for myocardial infarction,
      yet research shows that women continue to experience prehospital care pathway
      delays. METHODS: A 1-year prospective census was carried in six major academic
      teaching hospitals in Dublin, Ireland in 2001-2002. A total of 277 (31%) female
      and 613 (69%) male patients with confirmed myocardial infarction were included in
      the study. RESULTS: Women were more likely to experience prolonged 'initial
      symptom-onset to A&E delays' (14 hours vs. 2.8 hours P < 0.0001), and 'intense
      symptom-onset to A&E delays' (3.1 hours vs. 1.8 hours , P < 0.0001), i.e. arrival
      at a hospital accident and emergency department. Advancing age was associated
      with greater prehospital delays (P < 0.0001), whilst patients with private health
      insurance had shorter delays than public patients (without private health
      insurance) or those with medical cards (entitling them to means-tested medical
      benefits) (P = 0.001). Patients who drove themselves by car to hospital had
      shorter median prehospital times than those arriving by any other admission mode
      (P < 0.0001), whilst those referred by their general practitioner had longer
      delays than those who were self-referred (5 hours vs. 1.7 hours, P < 0.0001).
      CONCLUSIONS: Female gender, advancing age, referral source, insurance status and
      mode of transport to hospital are independent factors contributing to prehospital
      patient delays. Nurses who care for patients with coronary artery disease have a
      unique opportunity to educate people about the most appropriate action to be
      taken in the event of experiencing symptoms.

PMID- 16441532
TI  - Impact of a rheumatology expert nurse on the wellbeing of patients attending a
      drug monitoring clinic.
AB  - AIM: This paper reports a study to test the hypothesis that consultation with a
      clinical nurse specialist in a drug monitor clinic has a measurable impact on the
      well-being of patients with rheumatoid arthritis. METHOD: A single blinded
      randomized controlled trial was carried out with 71 patients with rheumatoid
      arthritis who were starting new disease-modifying anti-rheumatic therapy at a
      district general hospital. Patients were randomized into two groups over a 3-year
      recruitment period. Intervention group patients were monitored by a rheumatology
      clinical nurse specialist using Pendelton's framework to assess patient needs
      alongside safety monitoring. Control group patients were seen by an outpatient
      staff nurse for safety monitoring only over a 1-year period. The primary outcome
      measures were the Arthritis Impact Measurement Scales and the Rheumatology
      Attitude Index. Data were also collected on the Disease Activity Score, number of
      consultations with healthcare professionals and changes in drug therapy. Data
      were collected at baseline, 3, 7 and 12 months between 1999 and 2002. RESULTS:
      The Intervention group had greater change scores than the Control group for the
      Arthritis Impact Scale, with statistical significance shown at 7 months (P =
      0.03). At 12 months the Rheumatology Attitude Index had improved by a mean of 1.8
      in the Intervention group and deteriorated by 0.3 in the Control group. Changes
      in the Disease Activity Score were greater in the Intervention group at all time
      points, with statistical significance at 12 months (P = 0.048). There was little
      difference in the number of consultations or changes in drug therapy between the
      two groups. CONCLUSION: Consultation with an expert rheumatology nurse in a drug
      monitor clinic may add value in terms of improving patients' perceived ability to
      cope with the arthritis.

PMID- 16441533
TI  - Spirituality and family nursing: spiritual assessment and interventions for
      families.
AB  - AIM: The aim of this paper is to propose a guideline for spiritual assessment and
      interventions explicitly for families, while considering each family member's
      unique spirituality. BACKGROUND: Spirituality's positive effect is pervasive in
      health care and in the lives of many families; therefore, there is a need to
      integrate spiritual assessment and interventions in total family care.
      DISCUSSION: The majority of published guidelines on spiritual assessment and
      interventions are designed predominantly for individuals. They fail to
      differentiate between individual and family spirituality or offer only brief
      discussions on family spirituality. Such guidelines are potentially problematic.
      They may lead nurses to focus only on individual spirituality and neglect to
      discern family unit spirituality or recognize the presence of conflicts in
      spiritual perspectives within the family. While other disciplines such as social
      work and family therapy have several guidelines/strategies to assess family
      spirituality, there is a dearth of such guidelines in the family health nursing
      and spirituality literature, in spite of the rhetoric about incorporating
      spirituality as part of total family assessment. As a beginning solution,
      guidelines are proposed for spiritual assessment and interventions for the family
      as a unit, and the category of spiritual interpretation to represent diagnosis is
      introduced. Case studies exemplify how to integrate the guideline, and illustrate
      elements that may favour specific interpretations which would guide the
      interventions. CONCLUSION: As nurses continually strive to assist families with
      their health needs, they must also attend to their spiritual needs, as one cannot
      truly assess a family without assessing its spirituality.

PMID- 16441534
TI  - Stage of exercise and health-related quality of life among overweight and obese
      adults.
AB  - AIM: This paper reports a study whose main aim was to understand the correlation
      between stages of exercise and health-related qualities of life among overweight
      and obese adults in Taiwan. BACKGROUND: Regular exercise has been shown to
      improve health-related quality of life in the general population and among
      patients with chronic diseases. Nevertheless, systematic investigations of the
      correlation between exercise stages and the health-related quality of life among
      overweight and obese adults are lacking in Taiwan. METHOD: A cross-section of
      people from the weight loss clinics of a medical centre in Taipei was recruited
      to the study. The Chinese version of the Stages of Exercise and the Taiwanese
      version of Short Form 36 questionnaires were used to collect data from those
      whose body mass indexes were equal to or >24 kg/m2. The data were collected in
      2003. RESULTS: In total, 212 overweight and obese adults participated in the
      study. The majority were in the preparation (38.2%) or contemplation (31.6%)
      stages of exercise; relatively few were in the action (14.2%) or maintenance
      (11.3%) stages, and the smallest number (4.7%) were in the precontemplation
      stage. Although over 70% of respondents were not in the habit of taking regular
      exercise, their motivations were very high. For the Short Form 36 scales, the
      highest scores were for physical functioning (84.5 +/- 17.3), while the lowest
      were for general health (55.5 +/- 20.9), vitality (59.8 +/- 18.1), and mental
      health (MH) (66.0 +/- 17.9). Different stages of exercise showed statistically
      significant differences within the eight domains of Short Form 36 (Wilks = 0.733,
      P = 0.001); a statistically significant difference was also found for physical
      functioning (P < or = 0.001), general health (P = 0.003), and vitality (P =
      0.005). CONCLUSION: Since stages of exercise are correlated with health-related
      quality of life among overweight and obese adults, healthcare providers need to
      understand what stages people are at in order to educate them to achieve a better
      quality of life and to motivate those who are inactive to do more exercise on a
      regular basis.

PMID- 16441535
TI  - Validity, trustworthiness and rigour: quality and the idea of qualitative
      research.
AB  - AIM: In this paper, I call into question the widely-held assumption of a single,
      more or less unified paradigm of 'qualitative research' whose methodologies share
      certain epistemological and ontological characteristics, and explore the
      implications of this position for judgements about the quality of research
      studies. BACKGROUND: After a quarter of a century of debate in nursing about how
      best to judge the quality of qualitative research, we appear to be no closer to a
      consensus, or even to deciding whether it is appropriate to try to achieve a
      consensus. The literature on this issue can be broadly divided into three
      positions: those writers who wish qualitative research to be judged according to
      the same criteria as quantitative research; those who believe that a different
      set of criteria is required; and those who question the appropriateness of any
      predetermined criteria for judging qualitative research. Of the three positions,
      the second appears to have generated most debate, and a number of different
      frameworks and guidelines for judging the quality of qualitative research have
      been devised over recent years. DISCUSSION: The second of the above positions is
      rejected in favour of the third. It argues that, if there is no unified
      qualitative research paradigm, then it makes little sense to attempt to establish
      a set of generic criteria for making quality judgements about qualitative
      research studies. We need either to acknowledge that the commonly perceived
      quantitative-qualitative dichotomy is in fact a continuum which requires a
      continuum of quality criteria, or to recognize that each study is individual and
      unique, and that the task of producing frameworks and predetermined criteria for
      assessing the quality of research studies is futile. CONCLUSION: Some of the
      implications of this latter position are explored, including the requirement that
      all published research reports should include a reflexive research diary.

PMID- 16441536
TI  - Qualitative meta-synthesis: a question of dialoguing with texts.
AB  - AIMS: This paper discusses whether useful synthesis of research reports across
      different qualitative methodologies is possible, and whether qualitative meta
      synthesis violates the tenets of the interpretive paradigm. BACKGROUND:
      Qualitative meta-synthesis is a recent development in qualitative inquiry that
      offers a means of enhancing the contribution of qualitative findings to the
      development of more formalized knowledge. However, there are a number of
      unanswered questions and areas that require debate. DISCUSSION: A brief overview
      of qualitative meta-synthesis as a method of inquiry is presented. The
      assumptions of phenomenology, ethnography and grounded theory are explored for
      their amenability to meta-synthesis and the possibility of coherent synthesis of
      findings across these methodologies. In addition, a summary of major
      philosophical commitments common to the interpretive paradigm is presented.
      Qualitative meta-synthesis as a methodology is then explored for its fit within
      this paradigm. An argument is made, with some caveats, for synthesis across
      qualitative methodologies. Gadamer's concepts of the hermeneutic circle, the
      fusion of horizons, and dialogue with the text are explored for the insight they
      provide into the place of qualitative meta-synthesis in inquiry. CONCLUSION: It
      is important for researchers to bring hermeneutic skill to the process of meta
      synthesis in order to develop a comprehensive understanding of the various
      philosophical assumptions in which qualitative approaches are based. The
      particular challenge of combining analysis and interpretation from studies with
      markedly different approaches and intentions may prompt synthesists to create new
      and innovative approaches to the presentation of meta-synthesis.

PMID- 16441537
TI  - Monitoring child and parent refusals to enrol in clinical research protocols.
AB  - AIMS: The aim of this paper is to report the rates and reasons for refusal given
      by 817 eligible participants from 10 completed and ongoing nursing and
      behavioural medicine studies in paediatric oncology from 1994 to 2004.
      BACKGROUND: Eligible participants have the right to accept or decline
      participation in research studies. Information about rates of refusal and reasons
      for refusal could be useful in determining participant-perceived burden related
      to study participation, in accurately estimating the time needed to accrue an
      adequate number of participants to achieve the study aims, and in interpreting
      study findings from certain groups of participants. METHODS: A 13-item survey
      form about study characteristics was completed prospectively for each study
      included in this report; categories of reasons for refusal were inductively
      identified and defined using a semantic content analytic technique. RESULTS: The
      overall rate of refusal was 23.6% (range: 6.7-46.7%). The studies that involved
      blood sampling or end-of-life decision-making had the highest refusal rates and
      an instrumentation study had the lowest. Eligible male participants had
      consistently higher rates of refusal than did females across the 10 studies. Nine
      categories of refusal were inductively identified, with the most commonly
      reported reason being the burden of the research methods. CONCLUSION: A careful
      informed consent process will still result in some refusals. The refusal rates
      reported here can be used to help future researchers more accurately estimate
      accrual periods for studies involving blood sampling or investigating sensitive
      topics in paediatric oncology.

PMID- 16441538
TI  - Psychometric evaluation of the Hendrich Fall Risk Model.
AB  - AIMS: The aim of this paper is to report a psychometric evaluation of the
      Hendrich Fall Risk Model. BACKGROUND: Thoroughly developed and tested instruments
      for assessment of fall risk are needed to identify patients at risk of falling,
      to enable the implementation of preventative measures. METHOD: Data from 1977
      patients/residents in 45 nursing homes and 7197 patients from 47 hospitals were
      evaluated in a cross-sectional survey. The internal consistency of the Hendrich
      Fall Risk Model was examined using the Kuder-Richardson Test. The dimensions of
      the model were revealed by exploratory factor analysis and the Care Dependency
      Scale was used to investigate construct validity. Using Spearman Rho the sum of
      weighted items was correlated with the sum of unweighted items to obtain
      information about the practicability of a weighted total score. The study was
      carried out in 2003. RESULTS: The internal consistency of the model was not high
      (alpha = 0.54). Additionally, factor analysis showed that the model had more than
      one dimension. The correlation between the fall risk model and Care Dependency
      Scale was quite high for hospital patients and the total group (Spearman Rho = 
      0.71 or -0.76 respectively, P < 0.01) and medium for nursing home residents
      (Spearman Rho = -0.51, P < 0.01). The total scores of the weighted and unweighted
      items correlated highly (Spearman Rho = 0.96, P < 0.01). CONCLUSIONS: The use of
      this risk model is not recommended for nursing homes. For hospitals, we advise
      the use of unweighted items.

PMID- 16441539
TI  - Impact of the perceived public image of nursing on nurses' work behaviour.
AB  - AIM: This paper reports a study comparing nurses' perceptions of their public
      image with their self-image, and examining how the relationship between their
      perceived public image and self-image was associated with their job performance
      and turnover intentions. BACKGROUND: The stereotypical public image of nursing is
      a major concern to nurses. However, it is relatively unknown how this image
      affects nurses. A few studies have investigated how nurses' interpretations of
      their public image affect their self-image and work behaviour. METHODS: A
      convenience sample of 346 Australian nurses participated in a questionnaire study
      in 2003. The results were analysed by t-test, polynomial regression and response
      surface analysis. Six participants from the survey participated in a focus group
      to provide further interpretation of the findings. RESULTS: Nurses rated their
      aptitude for leadership more positively than they thought the public viewed them.
      In contrast, nurses rated their image as being caring less negatively than their
      perceived public image. Job performance was predicted by self-image relating to
      leadership aptitude. On the contrary, the relationship between self-image and
      perception of the public image as being caring predicted job performance. When
      nurses perceived their public image as caring less positively than their self
      image, their job performance tended to improve. As for turnover intention, both
      self-image and perceived public images of having an aptitude for leadership and
      being caring were negatively related to intention to quit the job. CONCLUSION: To
      enhance nurses' job performance and reduce their turnover intentions, it is
      important to improve both the public image and self-image of nurses.

PMID- 16441540
TI  - The psychological effects of organizational restructuring on nurses.
AB  - AIM: This paper reports a comparison of nurses affected by the restructuring
      associated with healthcare organization mergers (1998-2000) in the United Kingdom
      and those of non-affected nurses in the UK. BACKGROUND: Restructuring, a feature
      of healthcare organizations for decades, has been associated internationally with
      negative outcomes for nurses. Despite this, no model to evaluate management of
      change factors and psychological stress processes has been operationalized and
      tested. METHOD: A sample of 351 Registered Nurses was recruited from southern
      England. Participants either worked in organizations that were within 6 months of
      merging or were not affected by mergers. On two occasions, 6 months apart, all
      were sent a questionnaire that had been formulated for the study. Questions
      related to the parts of the model being tested: restructuring initiatives (i.e.
      stressors) information and participation, coping action, and coping effectiveness
      (i.e. outcomes). The data were collected between 1998 and 2000. FINDINGS: Nurses
      affected by mergers reported statistically significantly higher restructuring
      initiatives before and after an event than non-affected nurses. Moreover, up to
      12 months after an event some affected nurses reported lower information and
      participation, and lower coping effectiveness (i.e. higher job insecurity, job
      stress, job pressure, lower job satisfaction, physical, psychological, and
      environmental quality of life) than non-affected nurses, which was consistent
      with the model's proposals. However, there was no difference between affected and
      non-affected nurses' coping action. CONCLUSION: The psychological effects of
      restructuring are linked with perceptions of low information and participation,
      and with negative outcomes for nurses. Managers, therefore, need to communicate
      information and encourage staff to participate in decisions about restructuring
      events.

PMID- 16441546
TI  - Protective effects of melatonin in experimental free radical-related ocular
      diseases.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine with a range of
      antioxidative properties. Melatonin is endogenously produced in the eye and in
      other organs. Current evidence suggests that melatonin may act as a protective
      agent in ocular conditions such as photo-keratitis, cataract, glaucoma,
      retinopathy of prematurity and ischemia/reperfusion injury. These diseases are
      sight-threatening and they currently remain, for the most part, untreatable. The
      pathogenesis of these conditions is not entirely clear but oxidative stress has
      been proposed as one of the causative factors. Elevated levels of various
      reactive oxygen and nitrogen species have been identified in diseased ocular
      structures. These reactants damage the structure and deplete the eye of natural
      defense systems, such as the antioxidant, reduced glutathione, and the
      antioxidant enzyme superoxide dismutase. Oxidative damage in the eye leads to
      apoptotic degeneration of retinal neurons and fluid accumulation. Retinal
      degeneration decreases visual sensitivity and even a small change in the fluid
      content of the cornea and crystalline lens is sufficient to disrupt ocular
      transparency. In the eye, melatonin is produced in the retina and in the ciliary
      body. Continuous regeneration of melatonin in the eye offers a frontier
      antioxidative defense for both the anterior and posterior eye. However, melatonin
      production is minimal in newborns and its production gradually wanes in aging
      individuals as indicated by the large drop in circulating blood concentrations of
      the indoleamine. These individuals are possibly at risk of contracting
      degenerative eye diseases that are free radical-based. Supplementation with
      melatonin, a potent antioxidant, in especially the aged population should be
      considered as a prophylaxis to preserve visual functions. It may benefit many
      individuals worldwide, especially in countries where access to medical facilities
      is limited.

PMID- 16441541
TI  - Establishing a definition for a nurse-led clinic: structure, process, and
      outcome.
AB  - AIM: This paper reports a study to define a nurse-led clinic by exploring the
      domains of structure, process and outcome. BACKGROUND: Nurse clinics have been
      introduced as a measure to support intermediate care after the acute phase of
      disease. Previous studies have been mainly descriptive, or have only addressed a
      particular aspect of clinic service. METHODS: This exploratory study was
      conducted in two phases. In the first phase, nurses from 34 clinics were
      interviewed. In the second phase, 162 clinic sessions were observed, and 162
      patients and 16 physicians were interviewed. The data were collected in 2001
      2003. RESULTS: The nurses who ran the clinics were very experienced, and
      resources were available to support their work. Over 80% of their work was
      independent or interdependent, involving skills such as adjusting medications,
      and initiating therapies and diagnostic tests according to protocols. The
      principal interventions were assessments and evaluations, and health counselling.
      The nurses rated 'management of symptoms', 'prevention of complications', and
      'client satisfaction' as the top three key indicators of their success. All
      patients studied showed improvement after the nurse clinic consultation, but the
      best rates were found in wound and continence clinics. Satisfaction scores for
      both nurses and clients were high. Physicians valued their partnership in care
      with the nurses, but were concerned about possible legal liability resulting from
      the advanced roles assumed by these nurses. CONCLUSIONS: A nurse clinic is an
      effective alternative model of ambulatory healthcare delivery that uses a
      holistic framework.

PMID- 16441547
TI  - Urinary melatonin: a noninvasive method to follow human pineal function as
      studied in three experimental conditions.
AB  - The aim of this study was to examine whether urinary melatonin, rather than
      urinary 6-sulfatoxymelatonin (aMT6s), can be used as an indicator of diurnally
      and seasonally changing melatonin secretion. The subjects (n=15) spent three
      separate 24-hr periods in a climatic chamber during winter (n=7) and summer
      (n=8). Blood and urine samples were obtained during each period at 2- to 5-hr
      intervals. Serum melatonin and urinary melatonin and aMT6s were assayed by
      radioimmunoassay. The serum melatonin levels increased nearly 10-fold from low
      daytime to high nocturnal values. The mean nocturnal increase of urinary
      melatonin was 1.7-fold and that of urinary aMT6s was 4.6-fold. Both urinary
      melatonin and aMT6s correlated significantly with area under the curve melatonin
      in serum during the night, during the day and throughout the entire 24-hr
      observation period in all cases. The ratio between urinary melatonin and aMT6s
      excretion showed significant diurnal variation, being ninefold higher at 16:00 hr
      than at 07:00 or at 09:00 hr. The ninefold decrease in the urinary
      melatonin/aMT6s excretion ratio between the evening and the morning may reflect
      increased liver metabolism of melatonin during the night. Both urinary melatonin
      and aMT6s are good indicators of melatonin secretion, but the variation is
      significantly smaller for the former molecule.

PMID- 16441548
TI  - Urinary 6-sulfatoxymelatonin levels and their correlations with lifestyle factors
      and steroid hormone levels.
AB  - Exposure to light at night, as experienced by rotating night shift workers, has
      been related to lower circulating levels of melatonin, a hormone with recognized
      cancer protective properties. However, little is known about the relationship of
      other lifestyle factors or endogenous sex steroid hormones with melatonin levels.
      We examined cross-sectional associations of age, reproductive and menopausal
      factors, body mass index (BMI), alcohol consumption, smoking history, night shift
      work, as well as several other breast cancer risk factors, and circulating sex
      steroid hormone levels with creatinine-adjusted morning urinary melatonin (6
      sulfatoxymelatonin, aMT6s) levels. Participants were 459 healthy, primarily
      premenopausal (age range 33-50 yr) women from the Nurses' Health Study II (NHS
      II). Using multiple linear regression, we computed least-square mean hormone
      levels across categories of lifestyle factors. Age was inversely related to aMT6s
      levels, particularly before menopause (premenopausal women, <or=39 yr versus
      >or=49 yr; aMT6s, 20.8 ng/mg versus 11.8 ng/mg creatinine; P for trend, 0.02). In
      multivariate analyses, BMI was significantly and inversely associated with aMT6s
      levels (P for trend, <0.01). Higher pack-years of smoking were associated with
      significantly lower aMT6s levels (never smoker versus 15+ pack-years, aMT6s =
      17.4 ng/mg versus 12.3 ng/mg creatinine; P for trend, 0.04). We also observed a
      positive association between parity and aMT6s levels (P for trend, <0.01), but no
      other reproductive factors nor any of the sex hormones (estradiol, progesterone,
      estrone, estrone sulfate, dehydroepiandrostenedione, dehydroepiandrostenedione
      sulfate, testosterone, and androstenedione), as measured either in the luteal or
      the follicular phase of the menstrual cycle, were significantly associated with
      aMT6s. In conclusion, higher age, BMI, and heavy smoking were significantly
      related to lower levels of melatonin, whereas parity was significantly associated
      with higher aMT6s levels. Melatonin levels may be one mechanism through which
      these factors influence the development of cancer, but more studies are needed to
      elucidate these mechanisms definitively.

PMID- 16441549
TI  - Chronic hypoxia modulates the function and expression of melatonin receptors in
      the rat carotid body.
AB  - Melatonin modulates the carotid chemoreceptor response to chemical stimuli, and
      chronic hypoxia changes circadian activities and carotid body function. The
      purpose of this study was to test the hypothesis that chronic hypoxia alters the
      function and expression of melatonin receptors in the rat carotid body. Effects
      of melatonin on the carotid responses to hypercapnic acidosis and to hypoxia were
      determined by spectrofluorometric measurement of cytosolic calcium ([Ca(2+)](i))
      in fura-2-loaded type-I (glomus) cells dissociated from carotid bodies obtained
      from normoxic (Nx) or chronically hypoxic (CH) rats breathing 10% oxygen for 4
      wk. In the Nx control, melatonin concentration dependently attenuated the peak
      [Ca(2+)](i) response to hypercapnic acidosis, whereas it augmented the
      [Ca(2+)](i) response to cyanide or deoxygenated buffer. Yet, melatonin enhanced
      the peak [Ca(2+)](i) responses to hypercapnic acidosis or hypoxia in the CH
      glomus cells. An agonist of melatonin receptors, iodomelatonin also elevated the
      hypercapnic or hypoxic responses in the CH groups. The melatonin-induced changes
      in the [Ca(2+)](i) responses were abolished by pretreatment with nonselective
      mt(1)/MT(2) antagonist, luzindole, and by MT(2) antagonists, 4-phenyl-2
      propionamidotetraline or DH97. These findings suggest a functional modulation of
      melatonin receptors in the glomus cells in chronic hypoxia. To evaluate the level
      of expression of the melatonin receptors, in situ hybridization study with
      antisense mt(1) and MT(2) receptor mRNA oligonucleotide probes was performed on
      the Nx and CH carotid bodies. There were significant increases in the expression
      of mt(1) and MT(2) receptors in the CH comparing with the Nx group. Taken
      together, our results suggest an upregulation of the carotid expression of
      melatonin receptors by chronic hypoxia, which modulates the carotid response to
      melatonin for the circadian influence on breathing.

PMID- 16441550
TI  - Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased
      diurnal serum melatonin level and an increased pancreatic melatonin-receptor
      status.
AB  - There are functional inter-relationships between the beta cells of the endocrine
      pancreas and the pineal gland, where the synchronizing circadian molecule
      melatonin originates. The aim of this study was to elucidate a putative
      interaction between insulin and melatonin in diabetic patients and a diabetic rat
      model. We analyzed glucose, insulin, and melatonin levels of type 2 patients, as
      well as type 2 diabetic Goto Kakizaki (GK) rats by radioimmunoassay. Expression
      of pancreatic melatonin and pineal insulin receptors, as well as arylalkylamine-N
      acetyltransferase (AANAT), was determined by real-time reverse transcriptase
      polymerase chain reaction (RT-PCR). The AANAT enzyme activity was measured in
      pineal homogenates. Diabetic patients showed a decrease in melatonin levels,
      while in the pancreas of GK rats an upregulation of the melatonin-receptor mRNA
      was determined. The pancreatic islets of GK rats showed expression of the mRNA
      for the pancreatic melatonin (MT1) receptor, which had previously been identified
      in rats and insulinoma (INS1) cells. Besides their presence in animal cells, the
      MT1-receptor transcript was also detected in human pancreas by RT-PCR. Whereas
      the rat pancreatic mRNA expression of the MT1-receptor was significantly
      increased, the activity of the pineal AANAT enzyme was reduced. The latter
      observation was in accordance with plasma melatonin levels. The insulin-receptor
      mRNA of the pineal gland was found to be reduced in GK rats. Our observations
      suggest a functional inter-relationship between melatonin and insulin, and may
      indicate a reduction of melatonin in the genesis of diabetes.

PMID- 16441551
TI  - Differential effects of melatonin and its downstream effector PKCalpha on
      subcellular localization of RGS proteins.
AB  - Regulators of G protein signaling (RGS) are proteins that bind specifically to
      activated Galpha subunits of heterotrimeric G proteins to terminate signaling by
      both Galpha and Gbetagamma subunits. Signal-induced RGS redistribution may affect
      their activity in G protein-mediated signaling. We have previously shown that
      melatonin and the cell permeable cGMP analog 8-bromo cGMP, which lead to protein
      kinase C (PKC) activation, enhanced cytoplasmic distribution of RGS10 and RGS2 in
      prostate carcinoma PC3-AR cells. In the present study, we transfected PC3-AR
      cells with myc-tagged Galphai/Galphaq specific RGS proteins RGS2, RGS4 and RGS10
      and examined the effects of melatonin, 8-bromo cGMP and PKC inhibitors on their
      nuclear-cytoplasmic partitioning. RGS10 and RGS2 were predominantly localized in
      the nucleus and perinuclear regions whereas RGS4 was mostly cytoplasmic in the
      PC3-AR cells. Melatonin and the cell permeable cGMP analog 8-bromo cGMP,
      previously found to activate PKCalpha in the PC3-AR cells, enhanced cytoplasmic
      localization of RGS10 and RGS2 but induced nuclear accumulation of RGS4. The
      isozyme specific PKC inhibitor GO6976 (PKCalpha and PKCbeta1) but not hispidin
      (PKCbeta) negated the effects of melatonin on RGS10, RGS2 and RGS4 localization.
      These findings indicate that PKCalpha, a downstream effector of the melatonin
      receptor, differentially affects nuclear/cytoplasmic localization of both Galphai
      and Galphaq specific RGS proteins. These observations provide further insight
      into melatonin's ability to fine-tune multiple membrane G-proteins signaling in
      cells.

PMID- 16441552
TI  - Inverse correlation between endogenous melatonin levels and oxidative damage in
      some tissues of SAM P8 mice.
AB  - To assess whether oxidative damage in some tissues was related to their melatonin
      concentration, endogenous melatonin levels and the age-linked protein and lipid
      damage in spleen, thymus and liver in 5-month-old SAM P8 mice were examined. The
      results show that high levels of melatonin in spleen and thymus correlate with
      lower protein and lipid damage. The liver, which had much lower melatonin
      concentrations than the other two tissues, had much higher levels of oxidatively
      damaged protein, as measured by carbonyl values. These results add new evidence
      concerning the protective role of endogenous melatonin as an antioxidant agent,
      and suggest that a treatment with this molecule might help to reduce age
      associated functional deficits in many organs, including those of the immune
      system.

PMID- 16441553
TI  - Melatonin prevents apoptosis induced by UV-B treatment in U937 cell line.
AB  - Melatonin influences circadian rhythms and acts as antioxidant and free radical
      scavenger. UV irradiation triggers multiple cellular events which lead to cell
      death, in particular to apoptosis; this process involves reactive oxygen species.
      Apoptotic machinery involves several pathways, in which mitochondria play crucial
      roles. In this work we have evaluated by means of cytometric, biochemical and
      ultrastructural approaches, if incubation of U937 promonocytic leukemia cells
      with melatonin may affect apoptotic behavior induced by UV-B. The cell line was
      treated with 1 mm melatonin before and after UV-B exposure. Melatonin
      pretreatment significantly reduced the number of apoptotic cells, as revealed by
      FITC Annexin-V and propidium iodide assays (P < 0.005), as well as attenuated
      mitochondria alterations, as shown by ultrastructural morphology, Mito Tracker
      and JC-1 staining, and cytochrome c (cyt c) release (P < 0.005). On the contrary,
      incubation with melatonin after UV-B exposure significantly protect U937 cells
      from UV-B induced alterations, showing a possible delay of the apoptotic
      machinery (as revealed by the presence of earlier stages of apoptosis and
      significant cyt c release). Our results suggest that, in our experimental model,
      melatonin may play a role as noncytotoxic anti-apoptotic compound and, at least
      in part, may protect U937 cells from UV-B induced mitochondria
      dysfunction/damage.

PMID- 16441554
TI  - Melatonin attenuates diabetes-induced oxidative stress in rabbits.
AB  - Oxidative stress is considered to be the main cause of diabetic complications. As
      the role of antioxidants in diabetes therapy is still underestimated, the aim of
      the present investigation was to study the antioxidative action of melatonin in
      comparison with N-acetylcysteine (NAC) under diabetic conditions. Alloxan
      diabetic rabbits were treated daily with either melatonin (1 mg/kg, i.p.), NAC
      (10 mg/kg, i.p.) or saline. Blood glutathione redox state and serum hydroxyl free
      radicals (HFR), creatinine and urea levels were monitored. After 3 wk of
      treatment animals were killed and HFR content, reduced glutathione/oxidized
      glutathione (GSH/GSSG) ratio as well as the activities of glutathione reductase,
      glutathione peroxidase and gamma-glutamylcysteine synthetase were estimated in
      both liver and kidney cortex. Diabetes evoked a several-fold increase in HFR
      levels accompanied by a significant decline in GSH/GSSG ratio in serum and the
      examined organs. In contrast to NAC, melatonin (at 1/10 the dose of NAC)
      attenuated diabetes-induced alterations in glutathione redox state and HFR
      levels, normalized creatinine concentration and diminished urea content in serum.
      Moreover, the indole resulted in an increase in glutathione reductase activity in
      both studied organs and in a rise in glutathione peroxidase and gamma
      glutamylcysteine synthetase activities in the liver. In contrast to NAC,
      melatonin seems to be beneficial for diabetes therapy because of its potent
      antioxidative and nephroprotective action. The indole-induced increase in the
      activities of the enzymes of glutathione metabolism might be of importance for
      antioxidative action of melatonin under diabetic conditions.

PMID- 16441555
TI  - Trans-pineal microdialysis in the Djungarian hamster (Phodopus sungorus): a tool
      to study seasonal changes of circadian clock activities.
AB  - The Djungarian hamster is a highly seasonal small mammal. The rhythmic secretion
      of melatonin by the pineal gland is under control of the circadian clock,
      conveying the photoperiodic message to the organism. Trans-pineal microdialysis
      permits the in vivo study of this well-defined and precise clock output by
      measuring melatonin release directly in the pineal gland. The aim of this study
      was to adapt this method to the Djungarian hamster in order to monitor clock
      properties during photoperiodic changes. Male adult Djungarian hamsters were kept
      in a long photoperiod (LD 16:8) and melatonin release was measured hourly during
      the dark period for several weeks. Melatonin showed a regular secretion between
      ZT 17 and ZT 23.5 whereas the amplitude became stable only after the third day of
      perfusion. To test how quickly changes in melatonin profile can be measured, 15
      min light pulses were given at different time points throughout the scotophase.
      Light-pulses immediately interrupted melatonin secretion at any time point during
      the scotophase and the temporal resolution for measurement could be reduced to 30
      min. In accordance with studies in the rat, long-term effects of light on the
      clock could only be observed when a light pulse was administered in the second
      half of the night. For the first time we established a method to measure
      precisely a direct and reliable clock-output in a highly seasonal species which
      allows us now to study the circadian and seasonal properties of the clock in
      detail.

PMID- 16441556
TI  - Parallel signaling pathways of melatonin in the pancreatic beta-cell.
AB  - Previous results demonstrated that melatonin inhibits cAMP production and
      stimulates IP(3) liberation in rat insulinoma INS1 cells, a model for the
      pancreatic beta-cell. This study addresses the impact of melatonin on insulin
      release. Insulin, cAMP and IP(3) levels of INS1 cells in a superfusion system
      were measured. Initially, forskolin was used to stimulate cAMP and subsequently
      insulin release. Incubation of forskolin (5 micromol/L)-stimulated cells with
      melatonin (100 nmol/L) inhibited cAMP and insulin levels (down to 60% of insulin
      and cAMP release). The G(i)alpha-protein-inhibitor pertussis toxin (PTX) was used
      to distinguish between the G(i)alpha-dependent cAMP pathway and the G(i)alpha
      independent IP(3) pathway. In our experiments we employed a specific stimulation
      pattern to prove proper inhibition of G(i)alpha-proteins by PTX. In INS1 cells
      incubated with 250 ng/mL PTX for 24 hr, melatonin was no longer able to inhibit
      the forskolin-induced cAMP and insulin release. In a study, carbachol was used to
      stimulate IP(3) and subsequently insulin release. Surprisingly, incubation of
      carbachol (300 micromol/L)-stimulated cells with melatonin (100 nmol/L) inhibited
      insulin release (down to 75% of insulin release). Finally, in PTX-incubated INS1
      cells, melatonin (100 nmol/L) increased carbachol (300 micromol/L)-induced
      insulin release (up to 124% of insulin release). In conclusion, we found that the
      melatonin MT(1)-receptor on pancreatic beta-cells is coupled to parallel
      signaling pathways, with opposite influences on insulin secretion. The cAMP- and
      subsequently insulin-inhibiting signaling pathway involves PTX-sensitive
      G(i)alpha-proteins and is predominant in terms of insulin release.

PMID- 16441557
TI  - Impairment of the melatonin rhythm in children with Sanfilippo syndrome.

PMID- 16441560
TI  - Muscles of facial expression in the chimpanzee (Pan troglodytes): descriptive,
      comparative and phylogenetic contexts.
AB  - Facial expressions are a critical mode of non-vocal communication for many
      mammals, particularly non-human primates. Although chimpanzees (Pan troglodytes)
      have an elaborate repertoire of facial signals, little is known about the facial
      expression (i.e. mimetic) musculature underlying these movements, especially when
      compared with some other catarrhines. Here we present a detailed description of
      the facial muscles of the chimpanzee, framed in comparative and phylogenetic
      contexts, through the dissection of preserved faces using a novel approach. The
      arrangement and appearance of muscles were noted and compared with previous
      studies of chimpanzees and with prosimians, cercopithecoids and humans. The
      results showed 23 mimetic muscles in P. troglodytes, including a thin sphincter
      colli muscle, reported previously only in adult prosimians, a bi-layered
      zygomaticus major muscle and a distinct risorius muscle. The presence of these
      muscles in such definition supports previous studies that describe an elaborate
      and highly graded facial communication system in this species that remains
      qualitatively different from that reported for other non-human primate species.
      In addition, there are minimal anatomical differences between chimpanzees and
      humans, contrary to conclusions from previous studies. These results amplify the
      importance of understanding facial musculature in primate taxa, which may hold
      great taxonomic value.

PMID- 16441561
TI  - An in situ hybridization study of Runx2, Osterix, and Sox9 at the onset of
      condylar cartilage formation in fetal mouse mandible.
AB  - Mandibular condylar cartilage is the principal secondary cartilage, differing
      from primary cartilage in its rapid differentiation from progenitor cells
      (preosteoblasts/skeletoblasts) to hypertrophic chondrocytes. The expression of
      three transcription factors related to bone and cartilage formation, namely
      Runx2, Osterix and Sox9, was investigated at the onset of mouse mandibular
      condylar cartilage formation by in situ hybridization. Messenger RNAs for these
      three molecules were expressed in the condylar anlage, consisting of
      preosteoblasts/skeletoblasts, at embryonic day (E)14. Hypertrophic chondrocytes
      appeared at E15 as soon as cartilage tissue appeared. Runx2 mRNA was expressed in
      the embryonic zone at the posterior position of the newly formed cartilage, in
      the bone collar and in the newly formed cartilage, but expression intensity in
      the newly formed cartilage was slightly weaker. Osterix mRNA was also expressed
      in the embryonic zone and in the bone collar, but was at markedly lower levels in
      the newly formed cartilage. Sox9 mRNA was continuously expressed from the
      embryonic zone to the newly formed cartilage. At this stage, Sox5 mRNA was
      expressed only in the newly formed cartilage. These results suggest that reduced
      expression of Osterix in combination with Sox9-Sox5 expression is important for
      the onset of condylar (secondary) cartilage formation.

PMID- 16441562
TI  - Morphogenesis of the second pharyngeal arch cartilage (Reichert's cartilage) in
      human embryos.
AB  - This study was performed on 50 human embryos and fetuses between 7 and 17 weeks
      of development. Reichert's cartilage is formed in the second pharyngeal arch in
      two segments. The longer cranial or styloid segment is continuous with the otic
      capsule; its inferior end is angulated and is situated very close to the
      oropharynx. The smaller caudal segment is in contact with the body and greater
      horn of the hyoid cartilaginous structure. No cartilage forms between these
      segments. The persistent angulation of the inferior end of the cranial or styloid
      segment of Reichert's cartilage and its important neurovascular relationships may
      help explain the symptomatology of Eagle's syndrome.

PMID- 16441563
TI  - Perinatal development of the pancreatic islet microvasculature in rats.
AB  - The aim of the present study was to investigate possible changes in the islet
      microvasculature during the period of pronounced beta-cell growth seen
      perinatally in rats. We studied islet endothelial and beta-cell proliferation, as
      well as islet vascular density, in rats during this period. There was a
      progressive increase in islet vascular density from day -1 to day 7 postpartum,
      with values similar to those in adult rats seen at the latter time point. (3)H
      thymidine-labelled islet endothelial cells were extremely rare in adult rats,
      whereas such cells were much more frequent perinatally. The beta-cell labelling
      index was higher in all perinatal animals than in adult rats, with peak values
      seen on day 2. The proliferating endocrine cells were located very close to blood
      vessels at day 2 after birth. In conclusion, the pronounced growth of islet
      endocrine cells seen during the first week after birth coincides and co-localizes
      with an even more pronounced increase in islet endothelial cell proliferation,
      which results in a marked increase in intra-islet vascular density. This
      perinatal increase in islet blood vessel density may facilitate glucose sensing
      and islet hormonal delivery to the systemic circulation.

PMID- 16441559
TI  - Genetic and epigenetic mechanisms in the early development of the vascular
      system.
AB  - The cardiovascular system plays a critical role in vertebrate development and
      homeostasis. Vascular development is a highly organized sequence of events that
      requires the correct spatial and temporal expression of specific sets of genes
      leading to the development of a primary vascular network. There have been
      intensive efforts to determine the molecular mechanisms regulating vascular
      growth and development, and much of the rationale for this has stemmed from the
      increasing clinical importance and therapeutic potential of modulating vascular
      formation during various disease states.

PMID- 16441564
TI  - In vivo fibreoptic confocal imaging (FOCI) of the human ocular surface.
AB  - Recent developments in the miniaturization of confocal imaging technology have
      resulted in the development of a hand-held confocal microscope probe. There are
      many structures of interest in the human eye that are within reach of a
      fluorescence-mode confocal microscope; this study assessed the feasibility of in
      vivo human ocular imaging. Safety analysis was undertaken to ensure that the
      laser light applied to the ocular surface structures constituted no threat to
      patient safety. A fibreoptic confocal imaging (FOCI) probe using an illumination
      wavelength of 488 nm was applied to the ocular surface of four volunteers after
      topical administration of sodium fluorescein. Stabilization of the probe on the
      ocular surface was difficult, but movement artefacts could be minimized to a
      satisfactory level in most subjects by a variety of procedures. High-quality
      images of conjunctival epithelial and goblet cells, lamina propria structures,
      accessory lacrimal glands, lacrimal ducts and superficial sclera were obtained.
      Lateral resolution was 1-1.5 microm and axial resolution was approximately 30
      microm; individual erythrocytes could be seen in conjunctival vessels. The rete
      ridges and intervening epithelial components, including the probable location of
      corneal limbal stem cells, could be viewed, although it was not possible to
      distinguish cell subgroups. The study showed that fluorescence-mode imaging of
      the ocular surface is a viable and promising tool for assessment of diseases and
      processes involving superficial ocular structures. Refinement of equipment and
      techniques, particularly probe stabilization, is necessary to realize fully the
      potential of FOCI for ocular use.

PMID- 16441565
TI  - Immunohistochemical localization of G protein betagamma subunits in the lateral
      wall of the rat cochlea.
AB  - The role of G protein-mediated signal transduction in the production of
      endolymph, an extracellular fluid of unusual ionic composition, is beginning to
      be understood. The identity of Galpha subunits in the stria vascularis and the
      spiral ligament of the lateral wall of the cochlear duct is well established.
      However, little is known about the presence of betagamma subunits. This study
      used immunohistochemistry to investigate the distribution of G protein betagamma
      subunits in the lateral wall of the cochlea. Temporal bones of 6- to 8-week-old
      rats were fixed in 4% paraformaldehyde and 0.1% glutaraldehyde and processed for
      embedding in paraffin wax. The dewaxed, midmodiolar sections of the cochlea were
      incubated with subunit-specific polyclonal antibodies. The results show that the
      pattern of immunoreactivity varies for the G protein beta1-4 and gamma1-3, 5 and
      7 subunits in the stria vascularis and spiral ligament. In the stria vascularis,
      immunoreactivity was detected for beta2, beta3, beta4, gamma1, gamma2 and gamma7
      subunits. All five types of fibrocytes in the spiral ligament exhibited positive
      staining for gamma2 and gamma7. However, immunoreactivity for beta1-4 subunits
      was variable. Immunoreactivity for gamma3 and gamma5 subunits was not detected in
      the lateral cochlear wall. The expression pattern of G protein betagamma subunits
      in lateral wall provides a basis for interpreting the functions of G protein
      coupled receptors in cochlear fluid homeostasis.

PMID- 16441566
TI  - The distribution of intermediate-conductance, calcium-activated, potassium (IK)
      channels in epithelial cells.
AB  - Intermediate-conductance, calcium-activated, potassium (IK) channels were first
      identified by their roles in cell volume regulation, and were later shown to be
      involved in control of proliferation of lymphocytes and to provide a K+ current
      for epithelial secretory activity. Until now, there has been no systematic
      investigation of IK channel localization within different epithelia. IK channel
      immunoreactivity was present in most epithelia, where it occurred in surface
      membranes of epithelial cells. It was found in all stratified epithelia,
      including skin, cornea, oral mucosa, vaginal mucosa, urothelium and the
      oesophageal lining. It occurred in the ducts of fluid-secreting glands, the
      salivary glands, lacrimal glands and pancreas, and in the respiratory epithelium.
      A low level of expression was seen in serous acinar cells. It was also found in
      other epithelia with fluid-exchange properties, the choroid plexus epithelium,
      the ependyma, visceral pleura and peritoneum, bile ducts and intestinal lining
      epithelium. However, there was little or no expression in vascular endothelial
      cells, kidney tubules or collecting ducts, lung alveoli, or in sebaceous glands.
      It is concluded that the channel is present in surface epithelia (e.g. skin)
      where it has a cell-protective role against osmotic challenge, and in epithelia
      where there is anion secretion that is facilitated by a K+ current-dependent
      hyperpolarization. It was also in some epithelial cells where its roles are as
      yet unknown.

PMID- 16441567
TI  - Thymocyte depletion affects neurotrophin receptor expression in thymic stromal
      cells.
AB  - Thymocytes and thymic stromal cells cross-talk in a bidirectional manner within
      the thymus, thus contributing to the generation of mature T-cells. The thymic
      stromal cells in the rat express the high- (TrkA, TrkB) and low-affinity (p75NTR)
      receptors for neurotrophins. In this study we analysed the regulation of TrkA,
      TrkB and p75NTR expression in the rat thymus by thymocytes. We induced thymocyte
      apoptosis by administration of corticoids in rats, and then analysed the
      expression and distribution of these receptors 1, 4 and 10 days later. Thymocyte
      death was assessed by the activation of caspase-3 in cells undergoing apoptosis.
      We observed massive thymocyte apoptosis 1 day after injection and, to a lesser
      extent, after 4 days, which was parallel with a reduction in the density of
      thymic epithelial cells normally expressing TrkA and p75NTR. Furthermore, TrkA
      expression was found in cortical thymic epithelial cells, which normally lack
      this receptor. The expression of TrkB was restricted to a subset of macrophage
      dendritic cells, and remained unchanged with treatment. The normal pattern of
      neurotrophin receptor expression was almost completely restored by day 10. The
      results demonstrate that the expression of neurotrophin receptors by thymic
      epithelial cells, but not by macrophage-dendritic cells, is regulated by
      thymocytes.

PMID- 16441568
TI  - The superior colliculus of the camel: a neuronal-specific nuclear protein (NeuN)
      and neuropeptide study.
AB  - In this study we examined the superior colliculus of the midbrain of the one
      humped (dromedary) camel, Camelus dromedarius, using Nissl staining and anti
      neuronal-specific nuclear protein (NeuN) immunohistochemistry for total neuronal
      population as well as for the enkephalins, somatostatin (SOM) and substance P
      (SP). It was found that, unlike in most mammals, the superior colliculus is much
      larger than the inferior colliculus. The superior colliculus is concerned with
      visual reflexes and the co-ordination of head, neck and eye movements, which are
      certainly of importance to this animal with large eyes, head and neck, and
      apparently good vision. The basic neuronal architecture and lamination of the
      superior colliculus are similar to that in other mammals. However, we describe
      for the first time an unusually large content of neurons in the superior
      colliculus with strong immunoreactivity for met-enkephalin, an endogenous opioid.
      We classified the majority of these neurons as small (perimeters of 40-50
      microm), and localized diffusely throughout the superficial grey and stratum
      opticum. In addition, large pyramidal-like neurons with perimeters of 100 microm
      and above were present in the intermediate grey layer. Large unipolar cells were
      located immediately dorsal to the deep grey layer. By contrast, small neurons
      (perimeters of 40-50 microm) immunopositive to SOM and SP were located
      exclusively in the superficial grey layer. We propose that this system may be
      associated with a pain-inhibiting pathway that has been described from the
      periaqueductal grey matter, juxtaposing the deep layers of the superior
      colliculus, to the lower brainstem and spinal cord. Such pain inhibition could be
      important in relation to the camel's life in the harsh environment of its native
      deserts, often living in very high temperatures with no shade and a diet
      consisting largely of thorny branches.

PMID- 16441569
TI  - Absence of large-diameter sensory fibres in a nerve to the cat humerus.
AB  - A fine branch of the median nerve innervates the periosteum and medullary cavity
      of the cat humerus. After branching to innervate the periosteum on the medial
      surface of the humerus, the nerve enters and supplies the medullary cavity via a
      nutrient foramen, accompanied by a small artery and vein. The composition of the
      fibres in the nerve was examined using electron microscopy. Myelinated fibres
      with diameters of 0.8-6.6 microm and unmyelinated fibres with diameters of 0.1
      1.4 microm were observed. These diameters indicate that afferent fibres of this
      nerve are confined within the Group III and IV categories, and may therefore be
      nociceptive or mechanoreceptive in function. In addition, autonomic efferent
      fibres may also be present in these fibre groups. As no fibre diameters greater
      than 7 microm were noted, it appears that Group I and II fibres are absent in
      this nerve. The fibre distribution suggests that the principal role of this nerve
      is to relay bone-related nociceptive or mechanoreceptive information to the
      central nervous system and to provide autonomic regulatory influences on the
      bone.

PMID- 16441572
TI  - Pneumocystis and Trypanosoma cruzi: nomenclature and typifications.
AB  - Published phylogenetic reclassifications of Pneumocystis as a fungus resulted in
      a nomenclatural shift from the Zoological Code to the International Code of
      Botanical Nomenclature. The same may be true for all microsporidians and sundry
      other organisms. This resulted in the invalidation of names and subsequently
      precipitated changes to the botanical code to accommodate Pneumocystis and
      microsporidian names. The repercussions following application of the 2005 Vienna
      Code to Pneumocystis nomenclature are detailed. Validity of the name for the
      human pathogen, Pneumocystis jirovecii, is re-established from its 1976
      publication under the Zoological Code, contrary to interpretation of validity
      under earlier botanical codes. Pneumocystis jirovecii is lectotypified and
      epitypified. The rat parasite, Pneumocystis carinii, is neotypified, separating
      it from Pneumocystis wakefieldiae. The original 1909 description of Trypanosoma
      cruzi, type species for Schizotrypanum, and causal agent of Chagas' disease,
      included parts of the life cycle of Pneumocystis. Trypanosoma cruzi is
      neotypified by the true Trypanosoma elements, thereby completing the
      nomenclatural separation from Pneumocystis and ensuring that Schizotrypanum is
      not applicable to Pneumocystis as an earlier name. The neotypes for P. carinii
      and T. cruzi represent the strains currently being investigated by their two
      respective genome projects. They were selected in light of their medical
      importance, physiological characterizations, and absence of lectotypifiable
      materials. The classification and nomenclature of Pneumocystis is reviewed and
      guidelines given for the publication of new species.

PMID- 16441574
TI  - Phospholipids of the differentiating species of Tetrahymena.
AB  - The whole-cell phospholipid composition of the six known polymorphic species of
      Tetrahymena has been examined by [(3)H]acetate and [(3)H]myristic acid
      radiolabeling, and by gas-liquid chromatography of total phospholipid-bound fatty
      acids. Five of the polymorphic species contained similar phospholipid profiles
      following radiolabeling in that phosphatidylethanolamine (PE) was the predominant
      phospholipid; however, in cells of Tetrahymena patula LFF,
      aminoethylphosphonolipid was present in amounts nearly equal to PE. Tetrahymena
      patula LFF contained an unusually large percentage of sphingolipid (16.2% by
      [(3)H]acetate radiolabeling). Substantial differences were found in the fatty
      acid profiles of the polymorphic species, which included the degree of fatty acid
      unsaturation and relative weight percentages of odd-chain fatty acids.
      Tetrahymena vorax contained a low ratio of unsaturated C(18) fatty acids to
      saturated C(18) fatty acids as compared with all other species examined. The
      differentiating species generally contained a lesser percentage of monoenoic
      fatty acids and a lower ratio of unsaturated C(16) fatty acids to saturated C(16)
      fatty acids as compared with the two monomorphic species examined.

PMID- 16441576
TI  - The particle inflow gun can be used to co-transform Paramecium using Tungsten
      particles.
AB  - A particle inflow gun (PIG) was constructed and tested for its utility to
      transform Paramecium using tungsten or gold as the DNA carrier particle. In the
      first set of experiments we transformed Paramecium with a plasmid containing the
      neomycin-resistance gene, obtaining a transformation efficiency of 0.31+/-0.14%
      (mean+/-SD) for tungsten particles and 1.30+/-0.29% for gold particles. Plasmid
      DNA precipitated upon tungsten was shown to be stable for transformation purposes
      for up to 1 h prior to use and had no detectable effects on transformation
      efficiency. In addition, we demonstrated that at high frequency (71+/-20%) a
      Paramecium mutant strain could be phenotypically rescued by co-transformation
      with a second plasmid containing the selectable neomycin-resistance gene. The PIG
      coupled with tungsten particles as the carrier offers a low-cost alternative for
      biolistic transformation of Paramecium.

PMID- 16441579
TI  - Intraspecific genetic variation in Paramecium revealed by mitochondrial
      cytochrome C oxidase I sequences.
AB  - Studies of intraspecific genetic diversity of ciliates, such as population
      genetics and biogeography, are particularly hampered by the lack of suitable DNA
      markers. For example, sequences of the non-coding ribosomal internal transcribed
      spacer (ITS) regions are often too conserved for intraspecific analyses. We have
      therefore identified primers for the mitochondrial cytochrome c oxidase I (COI)
      gene and applied them for intraspecific investigations in Paramecium caudatum and
      Paramecium multimicronucleatum. Furthermore, we obtained sequences of the ITS
      regions from the same strains and carried out comparative sequence analyses of
      both data sets. The mitochondrial sequences revealed substantially higher
      variation in both Paramecium species, with intraspecific divergences up to 7% in
      P. caudatum and 9.5% in P. multimicronucleatum. Moreover, an initial survey of
      the population structure discovered different mitochondrial haplotypes of P.
      caudatum in one pond, thereby demonstrating the potential of this genetic marker
      for population genetic analyses. Our primers successfully amplified the COI gene
      of other Paramecium. This is the first report of intraspecific variation in free
      living protozoans based on mitochondrial sequence data. Our results show that the
      high variation in mitochondrial DNA makes it a suitable marker for intraspecific
      and population genetic studies.

PMID- 16441582
TI  - Transfer of the members of the genus Brachiola (microsporidia) to the genus
      Anncaliia based on ultrastructural and molecular data.
AB  - Two microsporidian genera, AnncaliiaIssi, Krylova, & Nicolaeva 1993 and
      BrachiolaCali et al. 1998, possess a Nosema-type life cycle and unique cell
      surface ornamentations, which include precocious electron-dense coating of the
      plasmalemma and a variety of secretory structures deposited on the parasite
      surface and scattered in the host cell cytoplasm. Comparative analysis of
      ultrastructure of Anncaliia meligethi (the type species of the genus Anncaliia)
      and of B. vesicularum and B. algerae (the best-studied members of the genus
      Brachiola) clearly demonstrated that these microsporidia share many distinctive
      morphological features. The comparison of small subunit ribosomal DNA sequences
      showed high sequence identity of A. meligethi and B. algerae. Phylogenetic
      analyses indicated that the rDNA sequences of A. meligethi clustered with those
      of B. algerae suggesting a close relatedness of these microsporidia. The
      combination of molecular and morphological data provided clear evidence that
      these microsporidia belong to the same genus and therefore, warranted emendation
      of the genus Anncaliia and establishments of the following new combinations:
      Anncaliia vesicularum nov. comb., Anncaliia algerae nov. comb., Anncaliia connori
      nov. comb., and Anncaliia gambiae nov. comb. The generic name Brachiola is
      submerged according to the rule of priority.

PMID- 16441583
TI  - Characterization of an aldehyde dehydrogenase from Euglena gracilis.
AB  - The free-living protist Euglena gracilis showed an enhanced growth when cultured
      in the dark with high concentrations of ethanol as carbon source. In a medium
      containing glutamate/malate plus 1% ethanol, E. gracilis reached a density of 3 x
      10(7) cells/ml after 100 h of culture, which was 5 times higher than that
      attained with glutamate/malate or ethanol separately. This observation suggested
      the involvement of a highly active aldehyde dehydrogenase in the metabolism of
      ethanol. Purification of the E. gracilis aldehyde dehydrogenase from the
      mitochondrial fraction by affinity chromatography yielded an enrichment of 34
      times and recovery of 33% of the total mitochondrial activity. SDS-PAGE and
      molecular exclusion chromatography revealed a native tetrameric protein of 160
      kDa. Kinetic analysis showed Km values of 5 and 50 microM for propionaldehyde and
      NAD(+), respectively, and a Vm value of 1,300 nmol (min x mg protein)(-1). NAD(+)
      and NADH stimulated the esterase activity of the purified aldehyde dehydrogenase.
      The present data indicated that the E. gracilis aldehyde dehydrogenase has
      kinetic and structural properties similar to those of human aldehyde
      dehydrogenases class 1 and 2.

PMID- 16441584
TI  - Molecular phylogeny of a potentially parasitic dinoflagellate isolated from the
      solitary radiolarian, Thalassicolla nucleata.
AB  - Thalassicolla nucleata, a solitary radiolarian, has been described as being
      parasitized by two dinoflagellates, Solenodinium (Syndiniales) and Caryotoma
      (Blastodiniales). Several T. nucleata were stripped of their extracapsular
      material and allowed to regenerate their rhizopodial structures without
      symbionts. Within a week, two were observed to disintegrate, leaving behind non
      pigmented swimming dinoflagellate cells. Identical full-length ribosomal
      sequences were recovered from both samples. Upon alignment and phylogenetic
      analysis, it was determined that these putative parasite sequences were distinct
      from Scrippsiella nutricula (the dinoflagellate symbiont of the host), and also
      from all other dinoflagellate parasites sequenced to date.

PMID- 16441585
TI  - Variability in infection efficiency in vitro of different strains of the
      microsporidian Encephalitozoon hellem.
AB  - The infection efficiency of different strains of Encephalitozoon hellem of human
      origin was tested in Vero E6 cell cultures, scoring the number of infection foci
      (NIF) after 9, 14, 20, and 24 days of inoculation. The results revealed a strong
      interaction of the strain type with time: different strains showed different
      proliferative dynamics. Number of infection foci was lower on the first sampling
      day for CDC: V257, EHVS-96, and PV6-96, with a subsequent increase at a higher
      rate for the first strain and lower for the latter. In contrast, PV7-96 showed
      the highest NIF at the first sampling, followed by a slight decrease. Since these
      strains were selected by their genotype for the polar tube protein (PTP)-1A, 1B,
      1C, and 2C, respectively, it is tempting to suggest a major role of this protein
      in the differences detected, although the influence of other genes that
      hypothetically may also differ among the strains employed cannot be discarded.
      The different in vitro infection efficiencies raise the possibility that some
      strains of E. hellem will also produce more aggressive features in infected
      patients.

PMID- 16441586
TI  - Systenostrema alba Larsson 1988 (Microsporidia, Thelohaniidae) in the Dragonfly
      Aeshna viridis (Odonata, Aeshnidae) from South Siberia: morphology and molecular
      characterization.
AB  - An octospore microsporidium was found in the nymphs of Aeshna viridis, collected
      in intermittent streams near Novosibirsk, Siberia, Russia in 2003. Spores were
      uninucleate and measured 6.1+/-0.07 x 3.0+/-0.04 microm on fresh smears. The
      polar filament was anisofilar having 10-11 anterior coils (thicker filament
      diam.) and 10-11 posterior (thinner filament diam.) coils. Sporophorous vesicles
      were persistent and measured 12.3+/-0.23 x 11.9+/-0.20 microm. The infection was
      restricted to the adipose tissue and caused the formation of whitish "cysts"
      containing mature octospores. Based on ultrastructural similarity we consider
      this Siberian isolate to be Systenostrema alba, a species described from Aeshna
      grandis collected in Sweden (Larsson 1988). Maximum likelihood, neighbor joining,
      and maximum parsimony analyses of the small subunit rDNA all placed Systenostrema
      alba (Accession no. AY953292) as the sister taxon to a clade consisting of
      Thelohania solenopsae, Tubulinosema ratisbonensis, and Tubulinosema acridophagus.

PMID- 16441587
TI  - Redescription of Lagenophrys cochinensis Santhakumari & Gopalan, 1980
      (Ciliophora, Peritrichia, Lagenophryidae), an Ectosymbiont of Marine Isopods,
      including new information on morphology, geographic distribution, and
      intraspecific variation.
AB  - Lagenophrys cochinensis is a peritrich ciliate originally reported as an
      ectocommensal of the wood-boring isopods Sphaeroma terebrans, Sphaeroma triste,
      and Sphaeroma annandalei and the tanaidacean Apseudes chilkensis in estuaries of
      southern India. In the present study, it was found to occur also on Sphaeroma
      quoyanum, Sphaeroma walkeri, and Exosphaeroma planulum. New material was used to
      make permanent preparations, allowing a comprehensive description of the
      morphology of L. cochinensis for the first time. The macronucleus of L.
      cochinensis was found to have an elongate shape that spans the width of the cell
      body, unlike the compact macronucleus originally described. In addition, the
      loricae of all samples examined were subcircular or shorter than wide, not longer
      than wide as originally described. Polykinetid 3 of the infundibular
      infraciliature consisted of three rows of kinetosomes, only the third species of
      Lagenophrys found to have more than two rows in polykinetid 3 so far. Samples of
      L. cochinensis on S. quoyanum from New Zealand and California appeared to
      represent a population distinct from others. The species has a cosmopolitan
      distribution, probably owing to the ease with which its hosts are transported
      from one estuary to another in drifting wood or on hulls of ships.

PMID- 16441588
TI  - Transfusion Medicine History Illustrated. The hemotherapy of the barber surgeon.

PMID- 16441589
TI  - Hemotherapy: from bloodletting magic to transfusion medicine.

PMID- 16441590
TI  - Anti-D alloimmunization after D-mismatched allogeneic hematopoietic stem cell
      transplantation in patients with hematologic diseases.
AB  - BACKGROUND: The de novo development of anti-D after D-mismatched allogeneic
      hematopoietic stem cell transplantation (AHSCT) is a possibility that must be
      considered. The transfusion of D- blood components after AHSCT has been
      recommended but anti-D alloimmunization in this setting has been studied little.
      Thus, the aim of this study was to analyze anti-D formation after D-mismatched
      AHSCT. STUDY DESIGN AND METHODS: Thirty patients with a hematologic disease who
      underwent D-mismatched AHSCT were retrospectively studied. Support therapy
      included red blood cells (RBCs) and platelet (PLT) concentrates (PCs) from whole
      blood donations and PLTs from apheresis. After AHSCT, patients received D+ PCs
      without administering Rh immunoglobulin (RhIG). An antibody screening to detect
      anti-D was performed by low-ionic-strength saline-indirect antiglobulin test with
      the tube test. RESULTS: Fifteen D+ patients received stem cells (SCs) of D-
      donors and 15 D- patients received SCs of D+ donors. After AHSCT, patients
      received a median of 11.5 (range, 0-32) D- RBC units. D+ patients received 682
      (83%) of 825 PLT units from D+ donors, and D- patients received 573 (85%) of 678
      PLT units from D+ donors. None of the 30 patients developed anti-D after a median
      follow-up of 32 weeks (range, 4-310 weeks). CONCLUSION: Anti-D alloimmunization
      after performing a D-mismatched AHSCT is infrequent in patients with hematologic
      diseases although patients receive D-mismatched PLT transfusions without RhIG
      administration.

PMID- 16441591
TI  - Comparison of peripheral blood progenitor cell yield from standard chemotherapy
      used in the treatment of lymphoid malignancies and high-dose cyclophosphamide: a
      retrospective review of 141 patients.
AB  - BACKGROUND: Peripheral blood progenitor cells (PBPCs) are often collected after
      mobilization with high-dose cyclophosphamide (HDC) combined with growth factors.
      HDC may not be needed for PBPC mobilization, and patients with lymphoid
      malignancies can be harvested with treatment regimens of chemotherapy. STUDY
      DESIGN AND METHODS: A retrospective analysis was performed on 141 patients with
      lymphoma or multiple myeloma whose PBPCs were harvested after chemotherapy. The
      PBPC yield and time to mobilization was compared between patients who received
      HDC (n = 51) and other chemotherapy regimens (n = 90) including high-dose
      cyclophosphamide and etoposide (HDC plus VP-16; n = 41), CHOP, ESHAP, ABVD, VAD,
      and others (n = 49). A multiple linear regression model and proportional hazards
      model determined factors influencing yield and time to mobilization,
      respectively. RESULTS: The difference in mean yield between HDC and all non-HDC
      regimens was significant, with HDC plus VP-16 resulting in the highest yields.
      The proportion of patients achieving a CD34 count in excess of 5 x 10(6) per kg
      did not differ significantly between the regimens. In a multiple linear
      regression model, HDC plus VP-16 resulted in a higher PBPC yield than HDC but all
      other regimens did not. In addition, patients exposed to more than one prior
      chemotherapy regimen had lower yield regardless of the mobilization regimen. The
      mean number of days to mobilization with HDC was 10.2 days, 17.1 days for HDC
      plus VP-16, and 14.2 days for all other regimens. The timing of mobilization was
      influenced by the chemotherapy used and the number of prior regimens in a
      proportional hazards model. CONCLUSION: These results demonstrate a higher mean
      yield of PBPCs with HDC plus VP-16 but no difference in yield between non-HDC
      plus VP-16 regimens used for first-line or relapse therapy and HDC, suggesting
      that HDC may be an unnecessary additional therapy.

PMID- 16441592
TI  - A single dose of 6 or 12 mg of pegfilgrastim for peripheral blood progenitor cell
      mobilization results in similar yields of CD34+ progenitors in patients with
      multiple myeloma.
AB  - BACKGROUND: Current regimens for peripheral blood progenitor cell (PBPC)
      mobilization in patients with multiple myeloma are based on daily subcutaneous
      injections of granulocyte-colony-stimulating factor (G-CSF) starting shortly
      after cytotoxic therapy. Recently a polyethylene glycol-conjugated G-CSF
      (pegfilgrastim) was introduced that has a substantially longer t(1/2) than the
      original formula. STUDY DESIGN AND METHODS: The use of pegfilgrastim was examined
      at two dose levels for PBPC mobilization in patients with Stage II or III
      multiple myeloma. Four days after cytotoxic therapy with cyclophosphamide (4
      g/m(2)), a single dose of either 6 mg pegfilgrastim (n = 15) or 12 mg
      pegfilgrastim (n = 15) or daily doses of 8 microg per kg unconjugated G-CSF (n =
      15) were administered. The number of circulating CD34+ cells was determined
      during white blood cell (WBC) recovery, and PBPC harvesting was performed by
      large-volume apheresis. RESULTS: Pegfilgrastim was equally potent at 6 and 12 mg
      with regard to mobilization and yield of CD34+ cells. No dose dependence was
      observed because CD34+ cell concentration peaks were 131 and 85 per microL,
      respectively, and CD34+ cell yield was 10.2 x 10(6) and 7.4 x 10(6) per kg of
      body weight, respectively. Pegfilgrastim in either dose was associated with a
      more rapid WBC recovery (p = 0.03) and an earlier performance of the first
      apheresis procedure (p < 0.05) in comparison to unconjugated G-CSF. No difference
      regarding CD34+ cell maximum and yield could be observed. CONCLUSION: A single
      dose of 6 mg pegfilgrastim is equally potent as 12 mg for mobilization and
      harvest of PBPCs in patients with multiple myeloma. Because no dose dependency
      was seen at these dose levels, this might be also true for even smaller doses.

PMID- 16441593
TI  - Transient respiratory disturbance by granulocyte-colony-stimulating factor
      administration in healthy donors of allogeneic peripheral blood progenitor cell
      transplantation.
AB  - BACKGROUND: Allogeneic peripheral blood progenitor cell (PBPC) transplantation
      requires granulocyte-colony-stimulating factor (G-CSF) administration to mobilize
      PBPCs in healthy donors. The effects of G-CSF on pulmonary functions, however,
      have not been clearly elucidated in PBPC donors. STUDY DESIGN AND METHODS:
      Respiratory status by measurements of arterial blood gas was prospectively
      evaluated serially in 25 healthy donors (9 men, 16 women; age, 18-61 years)
      administered a dose of 10 microg per kg for 5 days. RESULTS: White blood cell
      (WBC) counts increased in all the subjects after G-CSF administration; means on
      Days 0, 3, and 5 were 6 x 10(9), 33.4 x 10(9), and 33.6 x 10(9) per L,
      respectively. The mean PaO(2) values on the respective days were 93.1, 85.8, and
      81.8 mmHg, and these changes were significant (p < 0.0001), remaining significant
      after adjustment for the WBC count. Levels of both PaCO(2) and AaDO(2) were
      significantly higher after G-CSF administration than those before G-CSF
      administration (p < 0.0001 and p = 0.0004, respectively). SaO(2) was
      significantly decreased after G-CSF administration (p = 0.0002). Age was
      identified as a significant predictive factor for the increase of AaDO(2) and
      PaO(2) decline. These observations clearly indicate that the gas exchange was
      significantly affected during G-CSF administration in healthy PBPC donors.
      CONCLUSION: Considering an increasing use of PBPC mobilization by G-CSF, careful
      monitoring of the respiratory status is important to ensure safety of PBPC
      donors, especially elderly donors.

PMID- 16441594
TI  - CD34+ cell adhesion molecule profiles differ between patients mobilized with
      granulocyte-colony-stimulating factor alone and chemotherapy followed by
      granulocyte-colony-stimulating factor.
AB  - BACKGROUND: High-dose therapy with autologous peripheral blood progenitor cell
      support is widely utilized but requires successful CD34+ cell mobilization and
      collection. Chemotherapy plus growth factors appear to mobilize more CD34+ cells
      than growth factors alone. Because alterations in expression of adhesion
      molecules are important in the trafficking of hematopoietic progenitors, the
      possibility was explored that the mechanism of this superior mobilization may be
      greater down regulation of adhesion molecules. STUDY DESIGN AND METHODS: The
      expression of eight adhesion molecules (CD11a, b, and c; 15s; 49d and e; 54; and
      62L) on the collected CD34+ cells from 15 patients undergoing mobilization with
      chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) was compared with
      those of 14 concomitant patients receiving G-CSF alone. RESULTS: Patients
      receiving chemotherapy plus G-CSF mobilized more CD34+ cells and did not differ
      in prior chemotherapy or radiation. There were no significant differences in the
      percentage of CD34+ cells expressing any of the adhesion molecules examined
      between the two groups. The chemotherapy plus G-CSF-mobilized cells consistently
      showed higher expression intensity, and this showed significance or a strong
      trend for CD11a and c, CD15s, and CD54. Despite these higher expression levels,
      there were no differences in engraftment kinetics. CONCLUSIONS: CD34+ cells
      mobilized by chemotherapy plus growth factors appear to have higher intensities
      of expression of several adhesion molecules. The significance of this observation
      will require further study.

PMID- 16441595
TI  - Maternal typing and test sufficiency in parentage analyses.
AB  - BACKGROUND: The contribution of maternal typing to paternity analysis was
      evaluated to determine how many additional loci to study in one-parent cases.
      STUDY DESIGN AND METHODS: Four groups underwent paternity analyses with an eight
      locus test battery. Files of 25 case trios were retrieved, in which alleged
      fathers had achieved paternity indices of greater than 100 ("included trios").
      Maternal types were omitted and the cases were reanalyzed ("included duos").
      Mother-child pairs of the cases were then coupled with unrelated men ("excluded
      trios"), and the cases were analyzed. Maternal types were omitted from the
      excluded trios and cases were reanalyzed ("excluded duos"). RESULTS: Paternity
      indices of men in included duos were markedly reduced when compared to included
      trios; odds were sufficiently low in 9 of 25 men that paternity remained in
      doubt. After omission of maternal phenotypes, excluded duos exposed 33 percent
      fewer genetic inconsistencies than excluded trios; 5 of 25 men in excluded duos
      demonstrated less than two genetic inconsistencies and 1 man had none. The
      specific probabilities of paternity exclusion in motherless cases averaged 61
      percent per locus of those in case trios. One random man in 52 duos was not
      excluded by the eight tests versus 1 in 417 trios. CONCLUSIONS: Omission of
      maternal typing from eight common microsatellite paternity tests reduced
      conclusive evidence for or against paternity by 30 to 40 percent. False inclusion
      of random men is an important failing of tests in motherless cases. Cases
      involving one parent and child (e.g., in immigration) would require examination
      of an additional five similar loci to compensate for absent maternal data. A
      change in standards is suggested.

PMID- 16441596
TI  - Platelet ADP response deteriorates in synthetic storage media.
AB  - BACKGROUND: During storage under blood bank conditions, platelets (PLTs) are
      known to secrete ADP. PLT stimulation by ADP results in refractoriness to
      restimulation, making this response one of the most unstable PLT reactions. The
      goal of this study was to evaluate the ADP-induced responses of PLTs stored in
      full plasma or in plasma and additive solution (AS). STUDY DESIGN AND METHODS:
      Surface expression of P-selectin, ADP-induced aggregation, and reconstituted
      whole-blood thrombus formation were determined on collagen surfaces in a
      perfusion model with PLTs that were stored for 4 days either in plasma or in the
      presence of plasma with PAS-II or Composol. RESULTS: After 4 days of storage in
      PAS-II but not in Composol, the percentage of PLTs that had secreted granule
      contents (P-selectin) was increased, when compared to PLTs stored in full plasma.
      Maximal aggregation in response to ADP was reduced for PLTs stored in PAS-II or
      Composol. Resuspension of these PLTs in plasma at 37 degrees C for 1 hour caused
      partial recovery of the aggregation response. Addition of apyrase to PLTs in AS
      preserved the responsiveness toward ADP. Titration experiments indicated that
      this response gradually decreased with decreasing plasma concentration. The
      functional significance of these findings was demonstrated by perfusion
      experiments. Thrombus formation on collagen was significantly higher for PLTs
      stored in full plasma than for PLTs stored in PAS-II or Composol. CONCLUSIONS:
      Storage of PLTs in the presence of AS under blood bank conditions induces
      deterioration of the PLT responsiveness to ADP compared to PLT concentrates in
      100 percent plasma. Higher plasma-to-AS ratios result in better preserved
      responses.

PMID- 16441597
TI  - Thiazole orange, a DNA-binding photosensitizer with flexible structure, can
      inactivate pathogens in red blood cell suspensions while maintaining red cell
      storage properties.
AB  - BACKGROUND: Development of a robust pathogen reduction system for red cells
      (RBCs) utilizing photosensitive dyes has been constrained by hemolysis, usually
      mediated by reactive oxygen species emanating from dye free in solution as well
      as dye bound to the RBC membrane. The RBC binding properties of thiazole orange
      (TO), a flexible nucleic acid intercalating cyanine dye that predominantly acts
      as a photosensitizer only when bound, were assessed along with its virucidal,
      bactericidal, and light-induced hemolytic activities. STUDY DESIGN AND METHODS:
      Leukodepleted 20% hematocrit RBCs suspended in Erythrosol (RAS-2) were
      oxygenated, inoculated with test organisms, incubated with TO, and illuminated.
      Control and treated samples were analyzed by appropriate assay. Identically
      prepared, but uncontaminated samples were phototreated, concentrated to 45%
      hematocrit, and assayed for potassium leakage, hemolysis, and ATP during storage.
      RESULTS: Approximately 21 percent TO bound to RBCs. Phototreatment inactivated
      from 5.4 to 7.1 log(10) of 5 tested viruses and from 2.3 to greater than 7.0
      log(10) of 8 tested bacteria. Phototreated RBCs exhibited only slightly increased
      hemolysis, moderately elevated potassium efflux, and similar levels of ATP
      compared to controls. CONCLUSION: TO can photoinactivate several model viruses
      and pathogens in RBCs under conditions that produce limited hemolysis without the
      addition of quenchers or competitive inhibitors.

PMID- 16441598
TI  - Evaluation of the enhanced bacterial detection system for screening of
      contaminated platelets.
AB  - BACKGROUND: The Pall third-generation enhanced bacterial detection system (eBDS)
      was recently approved for detection of bacterial contamination in leukoreduced
      platelets (PLTs). The method is based on the measurement of the oxygen content as
      a marker for bacteria. eBDS incorporates major modifications including removal of
      the sample-set filter, modification of the culture medium, and incubation with
      agitation of the sample pouch. STUDY DESIGN AND METHODS: Ten whole blood-derived
      random-donor PLT units collected on Day 1 after donation and 10 single-donor
      apheresis PLT units were spiked with low levels of bacteria in three different
      blood transfusion centers. Inoculation was performed at a final concentration of
      5 to 50 colony-forming units per mL with reference strains of five organisms
      involved in severe transfusion-associated infections. PLT units were stored at 22
      degrees C for 24 hours before sampling. Six sample sets were then sterile
      connected to each unit and placed on a horizontal agitator at 35 degrees C for 18
      or 24 hours of incubation. RESULTS: No false-positive results were obtained,
      indicating a 100 percent specificity of the assay. Of 126 spiked sample pouches
      tested, 61 of 63 (96.82%) and 63 of 63 (100%) were detected positive after 18 or
      24 hours of incubation, respectively. In the two missed cases that failed to
      detect Bacillus cereus, the measured oxygen was slightly above the detection
      threshold but was markedly different from the negative samples. CONCLUSION: The
      eBDS method allows definitive testing of PLTs as soon as 42 hours after
      collection and offers an alternative culture method to the BacT/ALERT system.

PMID- 16441599
TI  - Release of platelet-derived growth factors and proliferation of fibroblasts in
      the releasates from platelets stored in the liquid state at 22 degrees C after
      stimulation with agonists.
AB  - BACKGROUND: Fresh platelet (PLT)-rich plasma (PRP) treated with thrombin plus
      calcium chloride (CaCl(2)) is used to prepare a PLT gel to promote hemostasis and
      wound healing in a variety of surgical procedures. The effects of various
      agonists on stimulating the release of growth factors from liquid-preserved PLTs
      and the effects of the PLT releasate on the growth of fibroblasts in tissue
      culture were investigated. STUDY DESIGN AND METHODS: Plateletpheresis PLTs stored
      at 22 degrees C as high-yield PLTs for 3 to 6 days or outdated PLTs for 9 days
      were treated with agonists to assess release of platelet-derived growth factor
      (PDGF) AA, PDGF AB, PDGF BB, transforming growth factor-beta1 (TGF-beta1), and
      osteocalcin and the proliferation of fibroblasts treated with the PLT releasates
      in tissue culture. RESULTS: All treatments except for CaCl(2) alone and zeolite
      CaCl(2) produced significant increases in PDGF AA compared to PRP. Thrombin
      CaCl(2) produced significant increases in PDGF BB. Treatment by all the agonists
      produced similar increases in PDGF AB. TGF-beta1 and osteocalcin levels after
      treatment were similar to those in PRP. PRP releasate before and after
      stimulation with different agonists increased proliferation of fibroblasts in
      tissue culture. CONCLUSION: High-yield and outdated liquid-preserved PLTs
      released PDGF AA, AB, and BB but not TGF-beta1 or osteocalcin. The releasate from
      untreated PRP stimulated the proliferation of fibroblasts in tissue culture
      similar to the releasates from PRP treated with the different agonists. Further
      studies are needed to assess whether or not high-yield and outdated PLTs may be
      useful in wound healing.

PMID- 16441600
TI  - Controlled-rate versus uncontrolled-rate freezing as predictors for platelet
      cryopreservation efficacy.
AB  - BACKGROUND: Cryobiologic variables responsible for cell injuries and freezing
      techniques applicable in medical cryopractice should be revised and/or
      reengineered for minimizing cryoinjuries and maximizing cell recovery. In this
      study, the efficacy of different cryopreservation protocols based on platelet
      (PLT) recovery was evaluated. STUDY DESIGN AND METHODS: PLTs (n = 33) were
      prepared from whole-blood units. Cell count and viability, PLT morphologic score
      (PMS), and hypotonic shock response were determined. PLT surface antigens were
      measured by flow cytometry. Controlled-rate (with compensated fusion heat) and
      uncontrolled-rate freezing methods combined with 6 percent dimethyl sulfoxide
      were used. RESULTS: PLT recovery was superior in the controlled-rate setting
      (91.0 +/- 5.5 vs. 86.0 +/- 6.5; p < 0.05). PMS was significantly better in
      controlled-rate freezing (p < 0.01). GPIb/CD42b expression was reduced in both
      freezing groups versus control. GP140/CD62p expression was significantly (p <
      0.05) lower in the controlled-rate group and in both frozen groups was
      significantly higher than in the control groups. CONCLUSION: The use of strictly
      equalized (1 degrees C/min) controlled-rate freezing, combined with an
      intensified cooling rate (2 degrees C/min) during the liquid-to-solid-phase
      transition period, allows advanced quantitative and qualitative PLT recovery,
      even though the minor intergroup differences for some variables were observed.

PMID- 16441601
TI  - Washing platelets with new additive solutions: aspects on the in vitro quality
      after 48 hours of storage.
AB  - BACKGROUND: Rare clinical conditions cause the need for washed platelet (PLT)
      concentrates (PCs). Saline-washed PCs can only be stored shortly, however, owing
      to lack of substrates for PLT metabolism. New PLT additive solutions (PASs)
      contain such substrates and might be used alternatively. The in vitro quality of
      apheresis PCs washed with Composol-PS or modified PAS-III (PAS-IIIM) stored up to
      48 hours after wash was compared. STUDY DESIGN AND METHODS: Twelve blood donors
      underwent two apheresis procedures (A and B) collecting 6.0 x 10(11) PLTs in 500
      mL of plasma with a least 2 weeks in between. The PCs collected by Apheresis A
      were stored for 3 days and then split in two equal units before washing with
      Composol-PS or PAS-IIIM. The PCs collected by Apheresis B were split after
      collection. One unit was released for transfusion and 1 unit was stored unwashed
      up to Day 6 and used as reference unit. In vitro testing was performed before and
      after washing as well as 24 and 48 hours after wash. RESULTS: After 48 hours of
      postwash storage, the units washed with either PAS showed acceptable results for
      hypotonic shock response (HSR), P-selectin expression, and pH, whereas PLT
      aggregability was significantly impaired. Throughout the storage, unwashed units
      showed better in vitro quality. HSR and P-selectin expression were similar before
      and immediately after the washing procedure. CONCLUSION: Based on these in vitro
      results, 48-hour postwash storage of washed PCs with the two PASs seems to be
      feasible. In vivo recovery studies, however, must confirm this finding in the
      future.

PMID- 16441602
TI  - Recurrent acute hemolytic transfusion reactions by antibodies against Doa
      antigens, not detected by cross-matching.
AB  - An 81-year-old male patient suffered from recurrent acute hemolytic transfusion
      reactions after transfusion with phenotyped cross-match-negative red blood cells
      (RBCs). Extensive posttransfusion workup eventually revealed Dombrock (a) (Do(a))
      antibodies. Because commercially available cell panels do not allow for
      identification of anti-Do(a) and owing to the lack of Do(a) typing serum samples,
      selection of matched units of RBCs is dependent on negative cross-match results.
      In this case, selection of Do(a-) units by cross-matching failed, indicating that
      serologic methods were not reliable. A polymerase chain reaction with sequence
      specific priming assay was used to detect DOA and DOB alleles, which encode Do(a)
      and Do(b) antigens, respectively. The patient was confirmed to be DOB/DOB by DNA
      sequencing. Furthermore, the involved mismatched units in each of the three
      hemolytic episodes were shown to be Do(a+). In the presenting case, DNA typing
      appeared to be superior to serologic methods in selecting matched RBC units in
      the presence of anti-Do(a).

PMID- 16441603
TI  - Red blood cell alloantibodies after transfusion: factors influencing incidence
      and specificity.
AB  - BACKGROUND: Alloimmunization after exposure to red cell (RBC) alloantigens
      depends on genetic and acquired patient-related factors, dose and route of
      administration, and the immunogenicity of the antigen, but exact kinetics are
      still unknown. STUDY DESIGN AND METHODS: A 5-year retrospective multicenter study
      analyzing factors influencing the rate and specificity of RBC alloimmunization
      was performed, with special emphasis on the time interval between transfusion
      event and antibody detection. Included were clinically significant alloantibodies
      against the Rhesus, Kell, Duffy, Kidd, and MSs blood group systems. RESULTS:
      Multivariate analysis involving 1710 immunized patients revealed that time
      interval between transfusion and antibody tests was strongly associated with the
      antibody specificity. Anti-Jk(a) and anti-Jk(b) were predominantly found in
      patients tested within 3 months, whereas anti-K and anti-Fy(a) were the most
      encountered antibodies at more than 5 years after transfusion. Of all immunized
      patients, new antibodies were detected within 14 days after transfusion in 299
      patients (16.8%) and in 1479 patients (83.2%) after more than 14 days. Fifty
      percent of transfusion recipients were retested for alloimmunization because of a
      new transfusion indication. Eleven of 2932 patients (0.4%) retested up to 3 days
      after transfusion had formed new antibodies. CONCLUSION: The time interval
      between transfusion and antibody test was associated with RBC antibody
      specificity. Because RBC antibody tests after transfusion are not routinely
      performed, many antibodies may (not) be detected at the time of a new transfusion
      event, posing the transfusion recipient at risk for transfusion delay or a
      (delayed) hemolytic transfusion reaction. Routine RBC antibody screening at set
      time intervals after transfusion would reduce these risks.

PMID- 16441604
TI  - In vivo recovery and survival of apheresis and whole blood-derived platelets: a
      paired comparison in healthy volunteers.
AB  - BACKGROUND: Methods of platelet preparation may alter the recovery and survival
      characteristics of platelets following transfusion. As suggested by a recent
      clinical trial, platelet recovery may be better preserved with apheresis platelet
      preparations than with platelets prepared from whole blood by the platelet-rich
      plasma (PRP) method. STUDY DESIGN AND METHODS: In vivo platelet recovery and
      survival of autologous leukoreduced (LR) apheresis platelets and autologous
      filter-LR PRP platelets were compared in 22 healthy volunteers using a paired
      crossover design. On the same day, each participant gave one apheresis platelet
      donation and one whole blood donation from which platelets were recovered from
      the PRP. The sequence of donations was randomly assigned for each participant.
      Following 5 days of storage and bacterial screening, a sample from each platelet
      product was labeled with either (51)chromium or (111)indium (randomly assigned)
      and both samples were simultaneously re-infused into the original donor. Recovery
      and gamma-function platelet survival were calculated for each platelet product
      using the multiple hit mathematical model. RESULTS: Five day stored LR-apheresis
      platelets had 18.8 percent better recovery, and 32.9 percent longer gamma
      survival than filter-LR PRP platelets. Stored apheresis platelets had lower p
      selectin expression and higher morphology scores than stored PRP platelets.
      CONCLUSIONS: Filter-LR PRP platelet preparation appears to adversely affect
      platelet recovery and survival characteristics. The reasons for this effect are
      not clear. These results may not apply to all apheresis and PRP methods of
      platelet preparation.

PMID- 16441605
TI  - Demographic characteristics and risks for transfusion-transmissible infection
      among blood donors in Xinjiang autonomous region, People's Republic of China.
AB  - BACKGROUND: The recruitment and retention of voluntary, nonremunerated blood
      donors continues to be a challenge in China. Understanding donor demographics and
      donor characteristics is crucial for any blood center in developing strategies to
      recruit potential donors. STUDY DESIGN AND METHODS: The study population included
      all 29,784 whole blood donors from January 1 to December 31, 2003, at the Urumqi
      City Blood Center or one of its mobile blood collection buses. Demographic data,
      location, and frequency of donation and results of testing for transfusion
      transmissible infection (TTI) were evaluated. RESULTS: The typical blood donor in
      Urumqi is male, less than 36 years of age, and Han Chinese; has at least a high
      school education; is a first-time donor; and donated at a mobile blood collection
      bus. The majority, 71 percent, were first-time donors. Among all donors, the
      seroprevalence rate of TTI was 3.5 percent for first-time donors, 2.7 percent for
      donors who donated twice, and 2.1 percent for donors who had donated three or
      more times. Han Chinese had lower seroprevalence rates of TTIs than ethnic
      minorities. Lower seroprevalence rates of TTIs were found among donors at mobile
      buses than at the blood centers. CONCLUSION: Similar to other donor populations,
      higher rates of TTIs were observed among first-time donors, and the prevalence
      decreased among repeated donors. One possible strategy for improving the safety
      of the blood supply might be for the blood center to recruit a cadre of donors
      who donate repeatedly, instead of relying on campaigns to recruit new donors from
      workplaces at each donation cycle.

PMID- 16441606
TI  - Self-reported symptoms associated with West Nile virus infection in RNA-positive
      blood donors.
AB  - BACKGROUND: In 2003, West Nile virus (WNV) nucleic acid amplification testing
      (NAT) was implemented to detect potentially infected donors. Of more than 5.3
      million donations screened prospectively by the American Red Cross during the
      epidemic periods of 2003 and 2004, 974 were NAT-reactive and 519 confirmed
      positive. A subset of both the confirmed-positive and the false-positive groups
      was assessed for demographic characteristics, symptoms, and symptom reporting
      relative to date of donation. STUDY DESIGN AND METHODS: All donors with initial
      WNV NAT-reactive results were invited to participate in a study that included a
      demographic, symptom, and date-of-symptom questionnaire. WNV confirmed-positive
      cases were compared to false-positive controls for comparison of frequency of
      symptom reporting before, on the day of, and after donation. RESULTS: Enrolled
      cases and controls were similar in all characteristics except cases were more
      likely to live in rural areas. Symptoms were reported by 61 percent of cases
      versus 20 percent of controls, with 74 percent of symptoms reported by cases
      within the 14 days after donation. The frequency of headache and fever reported
      together in the 7 days before donation was not significantly different between
      cases and controls; only the individual frequencies of headache, eye pain, and
      new rash during this time were significantly different. The most commonly
      reported symptoms, after adjustment for symptom reporting by controls, were
      headache, new rash, and generalized weakness; these symptoms were reported by 25
      percent of cases. CONCLUSIONS: The demographic characteristics of infected donors
      reflected the rural nature of the 2003 to 2004 WNV epidemics. This study suggests
      that asking donors about predonation headache and fever had no detectable
      contribution to blood safety.

PMID- 16441607
TI  - Worse quality of life in volunteer blood donors with hepatitis C.
AB  - BACKGROUND: Health-related quality of life (HRQOL) encompasses many different
      aspects of health perceived by the individual, and its alterations in patients
      with hepatitis C virus (HCV) have been recently reported. The objective was to
      study a population of volunteer blood donors at different stages of HCV liver
      disease. STUDY DESIGN AND METHODS: The Medical Outcomes Study 36-Item Short-Form
      Health Survey (SF-36), a generic tool, was used to evaluated HRQOL. The SF-36
      scores of HCV patients were compared with those of matched healthy blood donors
      and at the sixth month in those who were submitted to antiviral treatment. Sex,
      drug use, and alcohol consumption were also evaluated. A total of 120 HCV chronic
      carriers were divided into three groups: 1) patients with no indication for liver
      biopsy (n = 37); 2) patients submitted to liver biopsy with mild liver disease (n
      = 40); and 3) patients with moderate to severe liver disease submitted to
      interferon plus ribavirin treatment (n = 43). RESULTS: HCV patients had
      significantly lower SF-36 scores when compared with matched healthy blood donors.
      There was no correlation between SF-36 scores and history of intravenous and/or
      inhaled drug use or alcohol consumption. Women had lower SF-36 scores than men in
      six domains. At the sixth month of treatment, patients who continued to be
      positive for the presence of HCV RNA (nonresponders) had lower quality of life
      than those who became HCV RNA-negative. CONCLUSION: Healthy blood donors with HCV
      showed significantly reduced HRQOL that was more marked in women. The presence of
      the virus is one of the possible explanations for the reduced HRQOL.

PMID- 16441608
TI  - Donor reactions in high-school donors: the effects of sex, weight, and collection
      volume.
AB  - BACKGROUND: The high incidence of donor reactions in first-time, 17-year-old
      Caucasian whole-blood donors makes this group ideal for the study of donor
      reactions. STUDY DESIGN AND METHODS: Donor reaction rates were retrospectively
      evaluated in 7274 first-time, 17-year-old Caucasian whole-blood donors based on
      observations recorded at the collection sites. The effect of sex and weight on
      donor reactions was determined. In addition, a model was developed to estimate
      how different blood collection volumes would affect donor reaction rates.
      RESULTS: The donor reaction rate was 12.0 percent (870/7274). Female donors
      overall had a higher donor reaction rate than male donors (16.7% vs. 7.3%) and
      also had a higher donor reaction rate than male donors at each 20-lb weight
      interval in the range from 110 to 189 lb. A model suggested that a change in the
      blood-unit volume from 450 to 500 mL would increase donor reaction rates by 18
      percent in either female or male donors, whereas a reduction in the blood-unit
      volume from 500 to 400 mL would decrease donor reaction rates by 29 and 27
      percent in female and male donors, respectively. CONCLUSION: First-time, 17-year
      old Caucasian female donors had a higher donor reaction rate than male donors
      overall and at equivalent donor weights. In the range of present US blood-unit
      volumes, a change in collection of as little as 50 mL could have a significant
      impact on blood donor reaction rates in high-school students.

PMID- 16441609
TI  - Risk-behavior reporting by blood donors with an automated telephone system.
AB  - BACKGROUND: Donor risk-behavior assessment is important for blood safety. Few
      evaluations of automated telephone systems for eliciting risk exposure among
      voluntary blood donors have been reported. STUDY DESIGN AND METHODS: A modified
      risk-behavior questionnaire was presented after donation via an automated
      telephone polling system to 805 of 15,092 Hong Kong Chinese voluntary blood
      donors. Risk-behavior rates were compared to those of all other donors (14,287)
      simultaneously completing the questionnaire in a pencil-and-paper format.
      RESULTS: The telephone group included proportionally more women (46.3% vs.
      44.9%), previous donors (93.3% vs. 83.6%), and sexually inactive donors (66.5%
      vs. 71.2%) with lower educational achievement (60.7% vs. 54.5%). The telephone
      group demonstrated fewer missing data (mean 1.3%, range 0.4%-3.1% vs. mean 9.8%,
      range 8.0%-14.2%) and more complete demographic detailing, probably accounting
      for the demographic differences. The telephone group reported higher prevalence
      rates of needle or syringe sharing (1.5% vs. 0.3%), homosexual and/or bisexual
      intercourse (4.1% vs. 1.3%), knowing or suspecting that partner had intercourse
      with another during past year (12.4% vs. 8.5%), and future intention to use blood
      donation as a means to test for human immunodeficiency virus (HIV; 19.1% vs.
      13.7%). There was no difference in knowledge of the HIV window period or
      proportions visiting or using condoms with commercial sex workers between
      telephone and pencil-and-paper groups. CONCLUSION: This survey with automated
      telephone screening of potential blood donors revealed increased reporting of
      risk exposure relative to commonly used paper-and-pencil methods. This raises
      questions of possible underreporting of risk among blood donors screened by paper
      questionnaire and perhaps face-to-face interview.

PMID- 16441612
TI  - Staphylococcus aureus-contaminated apheresis platelets traced to donors' nasal
      carriage.

PMID- 16441610
TI  - Transfusion-associated Chagas disease (American trypanosomiasis) in Mexico:
      implications for transfusion medicine in the United States.
AB  - BACKGROUND: Trypanosoma cruzi, the protozoan cause of Chagas disease, causes life
      long infection and is easily transmitted by blood transfusion. Our goals were to
      determine the prevalence of Chagas disease among donors in five Mexican blood
      banks, to look for evidence of transmission of T. cruzi by transfusion, and to
      evaluate two serologic assays for Chagas disease. STUDY DESIGN AND METHODS: Blood
      samples from donors were tested initially with the Abbott Chagas EIA or the
      Meridian Chagas' IgG ELISA. Samples giving readings that were at least 50% of the
      cutoffs were run in a confirmatory radioimmune precipitation assay (RIPA), as
      were samples from recipients of blood products from RIPA-positive donors.
      RESULTS: The overall prevalence of Chagas disease was 1/133 (55/7,296; 0.75%). In
      addition, 4 of 9 surviving recipients of blood products from T. cruzi-infected
      donors were in turn infected. Using the manufacturers' recommended cutoffs, the
      sensitivity and specificity of the Abbott test were 92.0% (23/25) and 99.8%
      (2,865/2,872) respectively, and the corresponding values for the Meridian assay
      were 70.0% (21/30) and 100.0% (4,369/4,369). CONCLUSIONS: These findings indicate
      clearly that transfusion-associated transmission of T. cruzi is occurring in the
      study areas. Serologic testing of blood donors for Chagas disease should be
      performed there and in the rest of Mexico. The two screening assays evaluated may
      lack the accuracy necessary for blood donor testing when used as suggested by the
      manufacturers.

PMID- 16441611
TI  - Listeria monocytogenes in platelets: a case report.
AB  - BACKGROUND: Efforts to reduce bacterial contamination in platelets (PLTs) have
      led to implementation of tests for bacterial detection before product release.
      Although relatively rare as a human pathogen, Listeria monocytogenes often causes
      serious illness and has a case-fatality rate of 20 percent. CASE REPORT: PLTs
      from an asymptomatic 58- year-old Hispanic male with a long history of PLT
      donation were culture-positive for the presence of L. monocytogenes. The pulsed
      field gel electrophoresis (PFGE) pattern of the isolate matched two other L.
      monocytogenes isolates in the CDC National PulseNet database. Public health
      investigation found no evidence that the other two isolates were
      epidemiologically related to the PLT donor, who remained asymptomatic.
      CONCLUSION: A cluster of listeriosis cases was detected by PFGE but the
      significance is unknown. Organisms of public health significance should be
      reported to health departments. Better surveillance and reporting are needed in
      the efforts to improve blood product safety.

PMID- 16441613
TI  - Platelet senescent cultures and the predictive value of an early culture.

PMID- 16441617
TI  - The European standard for sun-protective clothing: EN 13758.
AB  - Clothing is considered one of the most important tools for sun protection.
      Contrary to popular opinion, however, some summer fabrics provide insufficient
      ultraviolet (UV) protection. The European Committee for Standardization (CEN),
      has developed a new standard on requirements for test methods and labelling of
      sun-protective garments. This document has now been completed and is published.
      Within CEN, a working group, CEN/TC 248 WG14 'UV protective clothing', was set up
      with the mission to produce standards on the UV-protective properties of textile
      materials. This working group started its activities in 1998 and included 30
      experts (dermatologists, physicists, textile technologists, fabric manufacturers
      and retailers of apparel textiles) from 11 European member states. Within this
      working group, all medical, ethical, technical and economical aspects of
      standardization of UV-protective clothing were discussed on the basis of the
      expertise of each member and in consideration of the relevant literature in this
      field. Decisions were made in consensus. The first part of the standard (EN 13758
      1) deals with all details of test methods (e.g. spectrophotometric measurements)
      for textile materials and part 2 (EN 13758-2) covers classification and marking
      of apparel textiles. UV-protective cloths for which compliance with this standard
      is claimed must fulfill all stringent instructions of testing, classification and
      marking, including a UV protection factor (UPF) larger than 40 (UPF 40+), average
      UVA transmission lower than 5%, and design requirements as specified in part 2 of
      the standard. A pictogram, which is marked with the number of the standard EN
      13758-2 and the UPF of 40+, shall be attached to the garment if it is in
      compliance with the standard. The dermatology community should take cognizance of
      this new standard document. Garment manufacturers and retailers may now follow
      these official guidelines for testing and labelling of UV-protective summer
      clothes, and the sun-aware consumer can easily recognize garments that definitely
      provide sufficient UV protection.

PMID- 16441618
TI  - A novel method of comparing the healing properties of two hydrogels in chronic
      leg ulcers.
AB  - Skin ulcers on the legs have a chronic, relapsing course and are often a
      significant management challenge. Novel methods of measuring and comparing the
      effects of different treatments can be of assistance in addressing this
      situation. A clinical pilot study using original methods was undertaken to
      compare the healing properties of the alginate gel Flaminal (test) and the
      hydrocolloid gel Intrasite (control) on chronic leg ulcers. The study was
      performed over a period of 28 days with two parallel groups of 10 patients. Both
      the surface (acetate tracing and planimetry) and the volume (Jeltrate mould
      impression and weighting) of each wound were measured at baseline and after 7, 14
      and 28 days of treatment. On both parameters results were superior with the test
      product compared to the control, with volume reduction being the first parameter
      to change. Between groups, difference in wound volume reduction was detected as
      early as day 7 whereas difference in surface reduction was clearly apparent only
      at day 28. Correlation between wound surface and volume reductions was also
      better in the test group (r = 0.843 vs. 0.421) than in the control. In
      conclusion, this pilot study suggests that combining wound surface and volume
      evaluations allows a more precise analysis of the healing process in venous leg
      ulcers and that this method is able to detect very early differences in
      treatments even with limited sample size.

PMID- 16441619
TI  - Psoralen cream plus ultraviolet A photochemotherapy (PUVA cream): our experience.
AB  - BACKGROUND: Psoralen ultraviolet A (PUVA) bath photochemotherapy has been proved
      highly effective in the treatment of various dermatoses without potential side
      effects of systemic therapy. Another form of topical PUVA therapy (PUVA cream)
      without the logistical requirements for bath tubs has recently been developed.
      OBJECTIVE: We sought to develop preparation and treatment standards to PUVA cream
      and to confirm its clinical efficacy in the treatment of various dermatoses.
      METHODS: In the first phase, the safety of a novel cream containing 0.002% 8
      methoxypsoralen (8-MOP) was determined in six healthy volunteers. In a second
      phase, 40 patients with different dermatoses were treated with a minor
      concentration (0.001% 8-MOP), following the guidelines for topical PUVA of the
      British Photodermatology Group. RESULTS: Plasma levels of psoralen after the
      application of the novel cream containing 0.002% 8-MOP, were less than 34 ng/mL,
      the maximum 8-MOP concentration reported for topical PUVA. With a minor
      concentration (0.001% 8-MOP), important improvement or healing was found in 53.3%
      of the cycles, generally with a good response since the first month of treatment.
      Only mild side-effects were detected in 14 patients. CONCLUSIONS: Based on our
      data, PUVA cream photochemotherapy is well accepted by patients and may be a
      highly effective treatment even if previous therapy was unsuccessful. In
      addition, PUVA cream is easier to use than PUVA bath.

PMID- 16441620
TI  - Frequency and distribution pattern of melanocytic naevi in Estonian children and
      the influence of atopic dermatitis.
AB  - BACKGROUND: There is a strong correlation between naevus number and prospective
      melanoma risk. Melanoma is one of the most rapidly increasing cancers in Estonia
      and primary prevention programmes for melanoma that target risk behaviour in the
      sun have so far not been launched. METHODS: The naevus profile was examined in
      549/700 9-year-old Estonian children (282 boys and 267 girls) and the presence of
      active atopic dermatitis (AD) was registered. RESULTS: There was a wide range of
      naevi (4-121) and a median total body count of 26. There was no difference in
      naevus count between boys and girls. No dysplastic naevi were found. Thirty-nine
      of 549 children (7%) had at least one lesion clinically diagnosed as a congenital
      naevus. Boys had more naevi on the face (median 4) and trunk (median 12) than
      girls (median 3 and 9, respectively, P < 0.001). Girls had more naevi on the legs
      compared with boys (median 4 and 3, respectively, P < 0.01). Fifty-four out of
      549 (9.8%) had naevi on the palms and 18/549 (3.3%) on the soles. Children with
      fair skin, freckles and light hair and eye colours had significantly more naevi
      than those with darker colours. Thirty-one of 549 (6%) children had AD diagnosed
      on the examination day and they had a lower total naevus count (median 20)
      compared with children with no AD (median 27, n = 518, P < 0.05). CONCLUSIONS:
      The naevus situation in Estonian children today might constitute a starting point
      for evaluating the efficiency of coming preventive measures as a change of naevus
      number in children might serve as an early marker for a change in melanoma
      incidence.

PMID- 16441621
TI  - The alteration of sister chromatid exchange frequencies in Behcet's disease with
      and without HLA-B51.
AB  - BACKGROUND: The analysis of sister chromatid exchange (SCE) is a cytogenetic
      technique used to show DNA damage as a result of an exchange of DNA fragments
      between sister chromatids. It is known that there is an increased SCE frequency
      in Behcet's disease (BD). OBJECTIVE: To investigate whether human leucocyte
      antigen (HLA)-B51-positive patients with Behcet's disease exhibit higher SCE
      frequencies than those without HLA-B51. METHODS: Lymphocytes from 75 patients (38
      women, 37 men) and from 50 controls (28 women, 22 men) were cultured in darkness
      for 72 h in the presence of bromodeoxyuridine. Metaphase chromosomes were stained
      with a fluorescence plus Giemsa technique after a standard harvest procedure. For
      HLA-B51 typing, DNA was extracted from ethylenediaminetetraacetic acid blood
      samples and HLA-B5 allele genotyping was performed by the polymerase chain
      reaction (PCR)-sequence specific primer method. RESULTS: Thirty-nine of 75
      patients with BD (52%) and 15 of 50 controls (30%) were found HLA-B51-positive.
      The SCE frequencies in HLA-B51-positive patients were higher than in HLA-B51
      negative ones (P < 0.001), whereas no difference was detected in the control
      group. CONCLUSION: This study revealed that there was a significant association
      between elevated SCE frequencies and existence of HLA-B51 patients with BD.

PMID- 16441622
TI  - A new formulation of an occlusive dressing containing betamethasone valerate 0.1%
      in the treatment of mild to moderate psoriasis.
AB  - BACKGROUND: Betamethasone valerate (BMV) is a medium-potency corticosteroid
      commonly used for the treatment of chronic psoriasis. Although occlusion has been
      shown to enhance the efficacy of BMV treatment, no ready-to-use occlusive BMV
      formulation is currently approved for the market. METHODS: Forty-two patients
      with mild to moderate psoriasis and with symmetrical lesions were treated with
      BMV 0.1% tape and BMV 0.12% cream for 30 days in a half-side distribution. Both
      treatments resulted in a significant clinical improvement. Efficacy and
      tolerability were evaluated by comparison of pre-treatment and post-treatment
      psoriasis area and severity index and self-administered psoriasis area and
      severity index scores, and by comparison of the changes from baseline in clinical
      appearance and hydration. RESULTS: Lesions treated with BMV 0.1% tape showed
      higher reductions from baseline in the psoriasis area and severity index and the
      self-administered psoriasis area and severity index scores (61.7% and 59.3%,
      respectively), compared with lesions treated with BMV 0.12% cream (39.5% and
      34.0%, respectively). No serious local or systemic treatment-related adverse
      effects were reported. CONCLUSIONS: Our results indicate a higher efficacy of BMV
      0.1% tape compared with BMV 0.12% cream in the treatment of mild to moderate
      chronic plaque psoriasis.

PMID- 16441623
TI  - What defines the quality of patient care in tinea pedis?
AB  - OBJECTIVES: The aim of this study has been to evaluate patients with tinea pedis
      for their demographic data and attitudes affecting the treatment of disease, and
      to compare the in vitro activity of 10 antifungal agents and to relate them to
      their in vivo activity. METHODS: Patients with positive mycological examination
      were enrolled in the study, and a questionnaire comprised of 22 questions was
      administered. A mycological culture was carried out for each specimen. The
      antifungal susceptibility of the subcultured species was determined for
      griseofulvin, terbinafine, ciclopiroxolamine, fluconazole, ketoconazole,
      itraconazole, bifonazole, sulconazole, oxiconazole and miconazole with
      microdilution. RESULTS: Mycological cultures were carried out from 59 patients
      and there were 35 positive cultures (59.3%). The dermatophytes were Trichophyton
      rubrum (n = 25) and Trichophyton mentagrophytes (n = 3). The yeasts were Candida
      albicans (n = 7), Candida glabrata (n = 1) and Trichosporon (n = 2). In the
      minimum inhibitory concentration (MIC) study, the mean +/- standard error of the
      mean (SEM) MICs of the antifungals for T. rubrum were as follows: terbinafine
      0.01 +/- 0.003, oxiconazole 0.16 +/- 0.05, sulkonazole 0.31 +/- 0.05, miconazole
      0.45 +/- 0.15, itraconazole 0.74 +/- 0.01, ketokonazole 1.03 +/- 0.17,
      ciclopiroxolamine 1.30 +/- 0.12, bifonazole 1.94 +/- 0.51, griseofulvin 4.87 +/-
      0.61, and fluconazole 17.91 +/- 3.67 microg/mL. CONCLUSION: Our study supports
      that azoles could be used as first-line treatment, as oxiconazole is very
      effective for both dermatophytes and C. albicans. Correlation between in vitro
      results and clinical outcomes of cases of dermatophytes is still to be
      established and interpretive breakpoints defined, in order to increase the
      quality of patient care in tinea pedis.

PMID- 16441624
TI  - A retrospective review of 20 hypertensive leg ulcers treated with mesh skin
      grafts.
AB  - BACKGROUND: Few articles have been published about hypertensive leg ulcers and
      their surgical treatment. Since mid of the year 2000, it has been our policy to
      treat all hypertensive leg ulcers very early with mesh split-thickness skin
      grafts. The present series consists of 15 patients whose hypertensive leg ulcers,
      including five bilateral cases, were treated with 20 mesh grafts from 2000 to
      2002. SUBJECTS AND METHODS: All patients, nine women and six men, had a long
      history of hypertension. The same surgical procedure was applied to all 15
      patients: a complete mechanical debridement of all necrotic tissues, immediately
      followed by mesh skin grafting. RESULTS: Patients were discharged from the
      hospital after an average post-operative period of 16 days. Upon leaving the
      hospital, the patients had lesions completely healed in 14 of 20 cases. The graft
      take had been complete after an average period of 14 days. In six cases, one or
      two very small patches of skin graft had necrosed and complete healing required
      an additional period of 1 to 3 months. In all 20 cases, pain had disappeared
      within 1 week from surgery. DISCUSSION: All patients were on opioid therapy
      before surgery. With medical treatment only, hypertensive leg ulcers used to heal
      after a mean period of 15 months. After surgery, the average healing period was 2
      weeks and opioids were stopped within 1 month after surgery. CONCLUSION: The
      review of the present series shows that early mesh grafting of hypertensive leg
      ulcers is beneficial, because healing is very quick and the pain will disappear
      quasi-instantly.

PMID- 16441626
TI  - Psoralen-ultraviolet A vs. narrow-band ultraviolet B phototherapy for the
      treatment of vitiligo.
AB  - BACKGROUND: Although many treatment modalities have been tried for the treatment
      of vitiligo, none is uniformly effective. Psoralen phototherapy (psoralen
      ultraviolet A (PUVA)) is established as efficacious treatment for vitiligo.
      Recently, narrow-band UVB (NBUVB) has been reported to be an effective and safe
      therapeutic option in patients with vitiligo. OBJECTIVE: To compare the efficacy
      of PUVA and NBUVB in the treatment of vitiligo. DESIGN AND SETTING: Retrospective
      analysis of 69 patients with vitiligo who were treated either with PUVA or NBUVB
      at the pigmentary clinic of the Dermatology Department of the Postgraduate
      Institute of Medical Education and Research, Chandigarh, India. OUTCOME MEASURES:
      The following variables were compared between the two groups of patients:
      repigmentation status, number of treatments for marked to complete repigmentation
      in existing lesions, appearance of new lesions or increase in size of existing
      lesions, adverse effect of therapy, stability of repigmentation and colour match.
      RESULTS: In PUVA-treated group, 9 patients showed marked to complete
      repigmentation (23.6%) and 14 patients showed moderate improvement (36.8%),
      whereas in NBUVB-treated group, 13 patients showed marked to complete
      repigmentation (41.9%) and 10 patients showed moderate improvement (32.2%). A
      statistically significantly better stability and colour match of repigmentation
      with surrounding skin was seen in NBUVB-treated patients. CONCLUSION: We showed
      that NBUVB is more effective than PUVA and repigmentation induced with NBUVB is
      statistically significantly more stable.

PMID- 16441625
TI  - The epidemiology of onychomycoses in Crete, Greece, between 1992 and 2001.
AB  - BACKGROUND: Onychomycosis represents the most frequently encountered nail
      disease, which is difficult to eradicate with drug treatment. Epidemiological
      studies concerning onychomycosis have been performed in many countries worldwide.
      Differences in the incidence of onychomycosis have been reported not only for
      various geographical areas, but also for different regions of the same country.
      OBJECTIVE: This survey was undertaken to determine the epidemiology of
      onychomycosis in the population of Crete, Greece. METHODS: In a prospective
      study, the fingernails and toenails of all new patients presenting to the
      outpatient Dermatology Department of the University Hospital of Crete were
      examined by certified dermatologists. If they appeared abnormal, nail material
      was obtained for mycologic examination. RESULTS: A total of 23,477 patients were
      examined during the study period (1992-2001). Of them, 19,556 (83.3%)
      participated in the investigation. Clinical abnormal nails were observed in 2098
      (10.7%) patients, 36.7% males and 63.3% females. Mycologically confirmed
      onychomycosis was detected in 511 (24.3%). Toenail onychomycosis was found in 283
      (55.4%) patients, fingernail onychomycosis in 210 (41%), and both toenail and
      fingernail onychomycosis in 18 (3.6%). In the toenail infections, dermatophytes
      were most frequently isolated (52%), followed by yeasts (24.7%) and moulds
      (15.5%); 7.8% of the infections were mixed. In the fingernail infections, yeasts
      were most often isolated (82.9%), followed by dermatophytes (10%), and moulds
      (1.9%); 5.2% of the infections were mixed. CONCLUSION: Because the pattern of
      onychomycoses in a country is changing with time, epidemiological studies are
      necessary for determining the prevalence and the causative agents of the
      infection.

PMID- 16441627
TI  - Psoriasis confined strictly to vitiligo areas--a Koebner-like phenomenon?
AB  - Vitiligo and psoriasis are both common skin disorders. However, psoriasis
      strictly confined to pre-existing vitiligo areas is rare and suggests a causal
      relationship. We report here on two patients with a strict anatomical
      colocalization of vitiligo and psoriasis. The histopathological examinations
      showed typical changes for both diseases together with a dense infiltrate of CD4+
      and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and
      tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell
      population, suggesting the functional activity of these cells and the creation of
      a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could
      identify anti-melanocytic T cells by tetramer staining and enzyme-linked
      immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger,
      by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma
      (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic
      predisposition for psoriasis.

PMID- 16441628
TI  - Naevus comedonicus of the scalp.
AB  - We report the case of a 3-year-old boy with naevus comedonicus, characterized by
      confluent clusters of dilated follicular orifices plugged with keratinous
      material that resemble open comedones, located on the scalp.

PMID- 16441629
TI  - Generalized granuloma annulare associated with chronic hepatitis B virus
      infection.
AB  - We describe a 63-year-old Chinese woman with generalized granuloma annulare (GGA)
      associated with chronic hepatitis B virus (HBV) infection for 10 years. She
      developed non-annular papule lesions after a previous infection of hepatitis B
      virus. Since then, her clinical course was aggressive with involvement of the
      trunk, extremities and neck. Histologically, granulomatous inflammations were
      found in the upper to mid dermis. The HBV DNA in these lesions was demonstrated
      by polymerase chain reaction (PCR). GGA was totally regressed after treatment of
      interferon-alpha for 3 months. To the best of our knowledge, GGA associated with
      chronic HBV infection has never been reported in literature. The prognostic
      significance of the association of granulomatous inflammation and virus infection
      is reviewed.

PMID- 16441630
TI  - Surgical reconstruction after subtotal ear resection in malignant melanoma of the
      ear.
AB  - Surgery in malignant melanoma of the external ear often leads to substantial
      defects where reconstruction poses a difficult challenge. We describe an option
      of a one-step ear reconstruction after subtotal ear resection in malignant
      melanoma surgery. In a patient with a high-risk melanoma of the helical rim, a
      wide local excision was performed. Because of a metastasis-suspect lymph node in
      the parotid gland, surgery included asservation of the sentinel lymph node, neck
      dissection and parotidectomy. A complete reconstruction of the ear was achieved
      using a bilobed flap from the retroauricular and neck region with acceptable
      cosmetic and functional results by one-step surgery. One micrometastasis was
      detected in the nuchal region but not in the marked sentinel lymph node. An
      adequate one-step ear reconstruction as described may also be performed to the
      benefit of patients with high-risk melanomas, allowing early adjuvant therapy.

PMID- 16441631
TI  - Keratoacanthoma developing in previous cryotherapy site for solar keratosis.
AB  - Keratoacanthoma is a relatively common benign squamous neoplasm that may show
      spontaneous clearing. Although the cause of the tumour is unknown, there are some
      reports describing keratoacanthoma following various types of trauma or secondary
      to other skin lesions. Thermal burns are reported to be important preceding
      traumas in the development of keratoacanthomas. whereas there is only one report
      of cold trauma of cryotherapy. We report a rare case of keratoacanthoma arising
      in the site of cryotherapy applied for solar keratosis.

PMID- 16441632
TI  - Pneumococcal cellulitis in an immunocompetent adult.
AB  - Streptococcus pneumoniae is a rare cause of cellulitis that develops mainly in
      patients with underlying chronic disease or those immunocompromised by drug or
      alcohol abuse. We report here a case of pneumococcal cellulitis in an
      immunocompetent patient.

PMID- 16441633
TI  - Intravenous cidofovir treatment for recalcitrant warts in the setting of a
      patient with myelodysplastic syndrome.
AB  - Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity
      against DNA viruses, including human papilloma virus (HPV). However, data on the
      efficacy of cidofovir in an immunosuppressive setting remain contradictory. We
      report for the first time on the promotion of the healing of recalcitrant warts
      in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.

PMID- 16441634
TI  - Detection of human papillomavirus type 34 in Bowen's disease on the pubic area.
AB  - We describe an 86-year-old man with Bowen's disease on the pubic area. The lesion
      was clinically a black-brownish keratotic nodule resembling seborrheic keratosis.
      Histopathological findings showed those of Bowen's disease and harboured human
      papillomavirus type 34 DNA. Genital, but not skin, human papillomaviruses are
      responsible for Bowen's disease on the skin.

PMID- 16441635
TI  - Barber's hair sinus in a female hairdresser: uncommon manifestation of an
      occupational dermatosis.
AB  - Hairdressers are prone to developing occupational skin diseases, particularly
      hand eczema of different origins. Rather uncommon, however, is the so-called
      barber's hair sinus that is caused by hair fragments penetrating the skin
      preferably in the interdigital spaces of their hands. Whereas, to date, the
      disease has almost exclusively been reported to occur on the hands of male
      hairdressers, we herein present the first case of a female hairdresser who
      developed a barber's hair sinus on one of her feet.

PMID- 16441636
TI  - Three cases of severe Rhus dermatitis in an English primary school.
AB  - We report three paediatric cases of severe allergic contact dermatitis caused by
      a Japanese lacquer tree (Rhus verniciflua), which is a rare specimen plant in the
      UK. The diagnosis of allergic contact dermatitis produced by plants that are not
      indigenous to a particular country is more likely to be delayed, as well as
      mistaken for cellulitis.

PMID- 16441638
TI  - RE: Ciprofloxacin resistance in Great Yarmouth and Waveney district.

PMID- 16441637
TI  - Amniotic membrane transplantation in the surgical management of symblepharon
      following toxic epidermal necrolysis.

PMID- 16441641
TI  - Axillary basal cell carcinoma.

PMID- 16441640
TI  - Molluscum contagiosum on a multicoloured tattoo.

PMID- 16441639
TI  - Primary carcinoma of ectopic axillary breast tissue.
AB  - The presence of ectopic breast tissue is reported in 2-6% of the general
      population with most cases being located in the axillary region. Although the
      same pathology occurs in both eutopic and ectopic breast tissue, primary
      carcinoma of ectopic breast tissue has been reported only in a small number of
      cases. Because an overlying accessory areola or nipple is often missing and
      because of a general lack of awareness among physicians and patients concerning
      these unsuspicious nodules, clinical diagnosis is frequently delayed.
      Histological diagnosis can also be delayed if ectopic breast tissue is not
      present or screened for in the biopsy specimens as apocrine glands of the breast
      and skin, respectively, exhibit striking similarities and immunohistochemistry is
      of limited help. Diagnostic delay is demonstrated by the case of a 56-year-old
      patient who underwent a series of four surgical excisions of a primary ectopic
      breast carcinoma and developed local lymph node metastasis until treatment with
      tamoxifen was started. As two-thirds of reported cases of primary ectopic breast
      carcinoma arose within the axillae, this case underlines the importance of a
      search for ectopic breast tissue in the context of axillary ductal carcinoma.

PMID- 16441642
TI  - Folliculitis spinulosa decalvans: failure to respond to oral isotretinoin.

PMID- 16441643
TI  - Fake sun tan diagnosis of porokeratosis.

PMID- 16441644
TI  - O'Brien actinic granuloma presenting as alopecia.

PMID- 16441645
TI  - Tufted hair folliculitis causing skullcap-pattern cicatricial alopecia.

PMID- 16441646
TI  - Subcutaneous mycosis produced by Aureobasidium pullulans in a renal transplant
      recipient.

PMID- 16441647
TI  - A case of pseudolymphomatous folliculitis.

PMID- 16441648
TI  - Response of predominantly recalcitrant cutaneous warts to topical chemotherapy.

PMID- 16441649
TI  - The distribution of pemphigus vulgaris-IgG subclasses in patients with active
      disease.

PMID- 16441650
TI  - Spontaneous repigmentation of vitiligo in an untreated HIV-positive patient.

PMID- 16441651
TI  - Darier's disease associated with horseshoe kidney.

PMID- 16441652
TI  - Alopecia in Vogt-Koyanagi-Harada syndrome.

PMID- 16441653
TI  - Shall we add trichilemmal cyst to painful skin tumours?

PMID- 16441655
TI  - Increased amylosucrase activity and specificity, and identification of regions
      important for activity, specificity and stability through molecular evolution.
AB  - Amylosucrase is a transglycosidase which belongs to family 13 of the glycoside
      hydrolases and transglycosidases, and catalyses the formation of amylose from
      sucrose. Its potential use as an industrial tool for the synthesis or
      modification of polysaccharides is hampered by its low catalytic efficiency on
      sucrose alone, its low stability and the catalysis of side reactions resulting in
      sucrose isomer formation. Therefore, combinatorial engineering of the enzyme
      through random mutagenesis, gene shuffling and selective screening (directed
      evolution) was applied, in order to generate more efficient variants of the
      enzyme. This resulted in isolation of the most active amylosucrase (Asn387Asp)
      characterized to date, with a 60% increase in activity and a highly efficient
      polymerase (Glu227Gly) that produces a longer polymer than the wild-type enzyme.
      Furthermore, judged from the screening results, several variants are expected to
      be improved concerning activity and/or thermostability. Most of the amino acid
      substitutions observed in the totality of these improved variants are clustered
      around specific regions. The secondary sucrose-binding site and beta strand 7,
      connected to the important Asp393 residue, are found to be important for
      amylosucrase activity, whereas a specific loop in the B-domain is involved in
      amylosucrase specificity and stability.

PMID- 16441656
TI  - Oligomerization states of the association domain and the holoenyzme of Ca2+/CaM
      kinase II.
AB  - Ca2+/calmodulin activated protein kinase II (CaMKII) is an oligomeric protein
      kinase with a unique holoenyzme architecture. The subunits of CaMKII are bound
      together into the holoenzyme by the association domain, a C-terminal region of
      approximately 140 residues in the CaMKII polypeptide. Single particle analyses of
      electron micrographs have suggested previously that the holoenyzme forms a
      dodecamer that contains two stacked 6-fold symmetric rings. In contrast, a recent
      crystal structure of the isolated association domain of mouse CaMKIIalpha has
      revealed a tetradecameric assembly with two stacked 7-fold symmetric rings. In
      this study, we have determined the crystal structure of the Caenorhabditis
      elegans CaMKII association domain and it too forms a tetradecamer. We also show
      by electron microscopy that in its fully assembled form the CaMKII holoenzyme is
      a dodecamer but without the kinase domains, either from expression of the
      isolated association domain in bacteria or following their removal by
      proteolysis, the association domains form a tetradecamer. We speculate that the
      holoenzyme is held in its 6-fold symmetric state by the interactions of the N
      terminal approximately 1-335 residues and that the removal of this region allows
      the association domain to convert into a more stable 7-fold symmetric form.

PMID- 16441657
TI  - Fatty acid synthesis. Role of active site histidines and lysine in Cys-His-His
      type beta-ketoacyl-acyl carrier protein synthases.
AB  - Beta-ketoacyl-acyl carrier protein (ACP) synthase enzymes join short carbon units
      to construct fatty acyl chains by a three-step Claisen condensation reaction. The
      reaction starts with a trans thioesterification of the acyl primer substrate from
      ACP to the enzyme. Subsequently, the donor substrate malonyl-ACP is
      decarboxylated to form a carbanion intermediate, which in the third step attacks
      C1 of the primer substrate giving rise to an elongated acyl chain. A subgroup of
      beta-ketoacyl-ACP synthases, including mitochondrial beta-ketoacyl-ACP synthase,
      bacterial plus plastid beta-ketoacyl-ACP synthases I and II, and a domain of
      human fatty acid synthase, have a Cys-His-His triad and also a completely
      conserved Lys in the active site. To examine the role of these residues in
      catalysis, H298Q, H298E and six K328 mutants of Escherichia colibeta-ketoacyl-ACP
      synthase I were constructed and their ability to carry out the trans
      thioesterification, decarboxylation and/or condensation steps of the reaction was
      ascertained. The crystal structures of wild-type and eight mutant enzymes with
      and/or without bound substrate were determined. The H298E enzyme shows residual
      decarboxylase activity in the pH range 6-8, whereas the H298Q enzyme appears to
      be completely decarboxylation deficient, showing that H298 serves as a catalytic
      base in the decarboxylation step. Lys328 has a dual role in catalysis: its charge
      influences acyl transfer to the active site Cys, and the steric restraint imposed
      on H333 is of critical importance for decarboxylation activity. This restraint
      makes H333 an obligate hydrogen bond donor at Nepsilon, directed only towards the
      active site and malonyl-ACP binding area in the fatty acid complex.

PMID- 16441658
TI  - Impact of the native-state stability of human lysozyme variants on protein
      secretion by Pichia pastoris.
AB  - We report the secreted expression by Pichia pastoris of two human lysozyme
      variants F57I and W64R, associated with systemic amyloid disease, and describe
      their characterization by biophysical methods. Both variants have a substantially
      decreased thermostability compared with wild-type human lysozyme, a finding that
      suggests an explanation for their increased propensity to form fibrillar
      aggregates and generate disease. The secreted yields of the F57I and W64R
      variants from P. pastoris are 200- and 30-fold lower, respectively, than that of
      wild-type human lysozyme. More comprehensive analysis of the secretion levels of
      10 lysozyme variants shows that the low yields of these secreted proteins, under
      controlled conditions, can be directly correlated with a reduction in the
      thermostability of their native states. Analysis of mRNA levels in this selection
      of variants suggests that the lower levels of secretion are due to post
      transcriptional processes, and that the reduction in secreted protein is a result
      of degradation of partially folded or misfolded protein via the yeast quality
      control system. Importantly, our results show that the human disease-associated
      mutations do not have levels of expression that are out of line with
      destabilizing mutations at other sites. These findings indicate that a complex
      interplay between reduced native-state stability, lower secretion levels, and
      protein aggregation propensity influences the types of mutation that give rise to
      familial forms of amyloid disease.

PMID- 16441659
TI  - Identification and characterization of 1-Cys peroxiredoxin from Sulfolobus
      solfataricus and its involvement in the response to oxidative stress.
AB  - Bcp2 was identified as a putative peroxiredoxin (Prx) in the genome database of
      the aerobic hyperthermophilic archaeon Sulfolobus solfataricus. Its role in
      oxidative stress was investigated by transcriptional analysis of RNA isolated
      from cultures that had been stressed with various oxidant agents. Its specific
      involvement was confirmed by a considerable increase in the bcp2 transcript
      following induction with H2O2. The 5' end of the transcript was mapped by primer
      extension analysis and the promoter region was characterized. bcp2 was cloned and
      expressed in Escherichia coli, the recombinant enzyme was purified and the
      predicted molecular mass was confirmed. Using dithiothreitol as an electron
      donor, this enzyme acts as a catalyst in H2O2 reduction and protects plasmid DNA
      from nicking by the metal-catalysed oxidation system. Western blot analysis
      revealed that the Bpc2 expression was induced as a cellular adaptation in
      response to the addition of exogenous stressors. The results obtained indicate
      that Bcp2 plays an important role in the peroxide-scavaging system in S.
      solfataricus. Mutagenesis studies have shown that the only cysteine, Cys49,
      present in the Bcp2 sequence, is involved in the catalysis. Lastly, the presence
      of this Cys in the sequence confirms that Bcp2 is the first archaeal 1-Cysteine
      peroxiredoxin (1-Cys Prx) so far identified.

PMID- 16441660
TI  - VEGF gene expression is regulated post-transcriptionally in macrophages.
AB  - The macrophage is critical to the innate immune response and contributes to human
      diseases, including inflammatory arthritis and plaque formation in
      atherosclerosis. Vascular endothelial growth factor (VEGF) is an angiogenic
      cytokine that is produced by macrophages. To study the regulation of VEGF
      production in macrophages we show that stimulation of monocyte-macrophage-like
      RAW-264.7 cells by lipopolysaccharide (LPS) increases expression of VEGF mRNA and
      protein. Three alternative splicing VEGF mRNA isoforms are produced, and the
      stability of VEGF mRNA increases following cellular activation. To study post
      transcriptional regulation of the VEGF gene the 3'-untranslated region (3' UTR)
      was introduced into the 3' UTR of the luciferase gene in a reporter construct. In
      both RAW-264.7 cells and thioglycollate-elicited macrophages, the 3' UTR sequence
      dramatically reduces reporter expression. Treatment with activators of
      macrophages, including LPS, lipoteichoic acid, and VEGF protein, stimulates
      expression of 3' UTR reporters. Finally, mapping studies of the 3' UTR of VEGF
      mRNA show that deletion of the heterogeneous nuclear ribonucleoprotein l binding
      site affects basal reporter expression in RAW-264.7 cells, but does not affect
      reporter activation with LPS. Together these results demonstrate that a post
      transcriptional mechanism contributes to VEGF gene expression in activated
      macrophage cells.

PMID- 16441661
TI  - Recruitment of transcription complexes to the beta-globin locus control region
      and transcription of hypersensitive site 3 prior to erythroid differentiation of
      murine embryonic stem cells.
AB  - Eukaryotic chromosomal DNA is densely packaged in the nucleus and organized into
      discrete domains of active and inactive chromatin. Gene loci that are activated
      during the process of cell differentiation undergo changes that result in
      modifications of specific histone tail residues and in loosening of chromatin
      structure. The beta-globin genes are expressed exclusively in erythroid cells.
      High-level expression of these genes is mediated by a locus control region (LCR),
      a powerful DNA regulatory element composed of several DNase I hypersensitive (HS)
      sites and located far upstream of the beta-globin genes. Here we show that RNA
      polymerase II and specific histone modifications that mark transcriptionally
      active chromatin domains are associated with the LCR core elements HS2 and HS3 in
      murine embryonic stem cells prior to differentiation along the erythroid lineage.
      At this stage HS3 is abundantly transcribed. After in vitro differentiation, RNA
      Polymerase II can also be detected at the embryonic epsilon- and adult beta
      globin genes. These results are consistent with the hypothesis that activation of
      the beta-globin gene locus is initiated by protein complexes recruited to the
      LCR.

PMID- 16441662
TI  - A simple in vivo assay for measuring the efficiency of gene length-dependent
      processes in yeast mRNA biogenesis.
AB  - We have developed a simple reporter assay useful for detection and analysis of
      mutations and agents influencing mRNA biogenesis in a gene length-dependent
      manner. We have shown that two transcription units sharing the same promoter,
      terminator and open reading frame, but differing in the length of their 3'
      untranslated regions, are differentially influenced by mutations affecting
      factors that play a role in transcription elongation or RNA processing all along
      the transcription units. In contrast, those mutations impairing the initial steps
      of transcription, but not affecting later steps of mRNA biogenesis, influence
      equally the expression of the reporters, independently of the length of their 3'
      untranslated regions. The ratio between the product levels of the two
      transcription units is an optimal parameter with which to estimate the efficiency
      of gene length-dependent processes in mRNA biogenesis. The presence of a
      phosphatase-encoding open reading frame in the two transcription units makes it
      very easy to calculate this ratio in any mutant or physiological condition.
      Interestingly, using this assay, we have shown that mutations in components of
      the SAGA complex affect the level of mRNA in a transcript length-dependent
      fashion, suggesting a role for SAGA in transcription elongation. The use of this
      assay allows the identification and/or characterization of new mutants and drugs
      affecting transcription elongation and other related processes.

PMID- 16441663
TI  - Generic normalization method for real-time PCR. Application for the analysis of
      the mannanase gene expressed in germinating tomato seed.
AB  - A generic sample normalization method applicable in relative comparison of mRNAs
      quantified with real-time polymerase chain reaction (PCR) is proposed. The method
      was applied in samples obtained from tomato seeds after osmopriming and aging
      treatments and from untreated seeds at early imbibition stage, when seeds had not
      completed germination. Normalization in sample variations was accomplished by
      detecting synthetic DNA sequences tailing cDNA after second strand reverse
      transcription synthesis, while the use of the common normalizer GAPDH proved
      unreliable. Results, obtained from the new method and having a standard error
      less than 10%, verified the expression profile of a germination-specific
      mannanase gene that was closely recorded at different time intervals in relation
      to seed germination.

PMID- 16441664
TI  - Limited mutagenesis increases the stability of human carboxypeptidase U (TAFIa)
      and demonstrates the importance of CPU stability over proCPU concentration in
      down-regulating fibrinolysis.
AB  - Procarboxypeptidase U [proCPU, thrombin-activatable fibrinolysis inhibitor
      (TAFI), EC 3.4.17.20] belongs to the metallocarboxypeptidase family and is a
      zymogen found in human plasma. ProCPU has been proposed to be a molecular link
      between coagulation and fibrinolysis. Upon activation of proCPU, the active
      enzyme (CPU) rapidly becomes inactive due to its intrinsic instability. The
      inherent instability of CPU is likely to be of major importance for the in vivo
      down-regulation of its activity, but the underlying structural mechanisms of this
      fast and spontaneous loss of activity of CPU have not yet been explained, and
      they severely inhibit the structural characterization of CPU. In this study, we
      screened for more thermostable versions of CPU to increase our understanding of
      the mechanism underlying the instability of CPU's activity. We have shown that
      single as well as a few 2-4 mutations in human CPU can prolong the half-life of
      CPU's activity at 37 degrees C from 0.2 h of wild-type CPU to 0.5-5.5 h for the
      mutants. We provide evidence that the gain in stable activity is accompanied by a
      gain in thermostability of the enzyme and increased resistance to proteolytic
      digest by trypsin. Using one of the stable mutants, we demonstrate the importance
      of CPU stability over proCPU concentration in down-regulating fibrinolysis.

PMID- 16441665
TI  - Crosstalk between Src and major vault protein in epidermal growth factor
      dependent cell signalling.
AB  - Vaults are highly conserved, ubiquitous ribonucleoprotein (RNP) particles with an
      unidentified function. For the three protein species (TEP1, VPARP, and MVP) and a
      small RNA that comprises vault, expression of the unique 100-kDa major vault
      protein (MVP) is sufficient to form the basic vault structure. To identify and
      characterize proteins that interact with the Src homology 2 (SH2) domain of Src
      and potentially regulate Src activity, we used a pull-down assay using GST-Src
      SH2 fusion proteins. We found MVP as a Src-SH2 binding protein in human stomach
      tissue. Interaction of Src and MVP was also observed in 253J stomach cancer
      cells. A subcellular localization study using immunofluorescence microscopy shows
      that epidermal growth factor (EGF) stimulation triggers MVP translocation from
      the nucleus to the cytosol and perinuclear region where it colocalizes with Src.
      We found that the interaction between Src and MVP is critically dependent on Src
      activity and protein (MVP) tyrosyl phosphorylation, which are induced by EGF
      stimulation. Our results also indicate MVP to be a novel substrate of Src and
      phosphorylated in an EGF-dependent manner. Interestingly, purified MVP inhibited
      the in vitro tyrosine kinase activity of Src in a concentration-dependent manner.
      MVP overexpression downregulates EGF-dependent ERK activation in Src
      overexpressing cells. To our knowledge, this is the first report of MVP
      interacting with a protein tyrosine kinase involved in a distinct cell signalling
      pathway. It appears that MVP is a novel regulator of Src-mediated signalling
      cascades.

PMID- 16441666
TI  - Yeast oxidative stress response. Influences of cytosolic thioredoxin peroxidase I
      and of the mitochondrial functional state.
AB  - We investigated the changes in the oxidative stress response of yeast cells
      suffering mitochondrial dysfunction that could impair their viability. First, we
      demonstrated that cells with this dysfunction rely exclusively on cytosolic
      thioredoxin peroxidase I (cTPxI) and its reductant sulfiredoxin, among other
      antioxidant enzymes tested, to protect them against H2O2-induced death. This
      cTPxI-dependent protection could be related to its dual functions, as peroxidase
      and as molecular chaperone, suggested by mixtures of low and high molecular
      weight oligomeric structures of cTPxI observed in cells challenged with H2O2. We
      found that cTPxI deficiency leads to increased basal sulfhydryl levels and
      transcriptional activation of most of the H2O2-responsive genes, interpreted as
      an attempt by the cells to improve their antioxidant defense. On the other hand,
      mitochondrial dysfunction, specifically the electron transport blockage, provoked
      a huge depletion of sulfhydryl groups after H2O2 treatment and reduced the H2O2
      mediated activation of some genes otherwise observed, impairing cell defense and
      viability. The transcription factors Yap1 and Skn7 are crucial for the
      antioxidant response of cells under inhibited electron flow condition and
      probably act in the same pathway of cTPxI to protect cells affected by this
      disorder. Yap1 cellular distribution was not affected by cTpxI deficiency and by
      mitochondrial dysfunction, in spite of the observed expression alterations of
      several Yap1-target genes, indicating alternative mechanisms of Yap1
      activation/deactivation. Therefore, we propose that cTPxI is specifically
      important in the protection of yeast with mitochondrial dysfunction due to its
      functional versatility as an antioxidant, chaperone and modulator of gene
      expression.

PMID- 16441667
TI  - Proton-decoupled 15N and 31P solid-state NMR investigations of the Pf3 coat
      protein in oriented phospholipid bilayers.
AB  - The coat proteins of filamentous phage are first synthesized as transmembrane
      proteins and then assembled onto the extruding viral particles. We investigated
      the transmembrane conformation of the Pseudomonas aeruginosa Pf3 phage coat
      protein using proton-decoupled 15N and 31P solid-state NMR spectroscopy. The
      protein was either biochemically purified and uniformly labelled with 15N or
      synthesized chemically and labelled at specific sites. The proteins were then
      reconstituted into oriented phospholipid bilayers and the resulting samples
      analysed. The data suggest a model in which the protein adopts a tilted helix
      with an angle of approximately 30 degrees and an N-terminal 'swinging arm' at the
      membrane surface.

PMID- 16441668
TI  - Methylene analogues of adenosine 5'-tetraphosphate. Their chemical synthesis and
      recognition by human and plant mononucleoside tetraphosphatases and dinucleoside
      tetraphosphatases.
AB  - Adenosine 5'-polyphosphates have been identified in vitro, as products of certain
      enzymatic reactions, and in vivo. Although the biological role of these compounds
      is not known, there exist highly specific hydrolases that degrade nucleoside 5'
      polyphosphates into the corresponding nucleoside 5'-triphosphates. One approach
      to understanding the mechanism and function of these enzymes is through the use
      of specifically designed phosphonate analogues. We synthesized novel nucleotides:
      alpha,beta-methylene-adenosine 5'-tetraphosphate (pppCH2pA), beta,gamma-methylene
      adenosine 5'-tetraphosphate (ppCH2ppA), gamma,delta-methylene-adenosine 5'
      tetraphosphate (pCH2pppA), alphabeta,gammadelta-bismethylene-adenosine 5'
      tetraphosphate (pCH2ppCH2pA), alphabeta, betagamma-bismethylene-adenosine 5'
      tetraphosphate (ppCH2pCH2pA) and betagamma, gammadelta-bis(dichloro)methylene
      adenosine 5'-tetraphosphate (pCCl2pCCl2ppA), and tested them as potential
      substrates and/or inhibitors of three specific nucleoside tetraphosphatases. In
      addition, we employed these p4A analogues with two asymmetrically and one
      symmetrically acting dinucleoside tetraphosphatases. Of the six analogues, only
      pppCH2pA is a substrate of the two nucleoside tetraphosphatases (EC 3.6.1.14),
      from yellow lupin seeds and human placenta, and also of the yeast
      exopolyphosphatase (EC 3.6.1.11). Surprisingly, none of the six analogues
      inhibited these p4A-hydrolysing enzymes. By contrast, the analogues strongly
      inhibit the (asymmetrical) dinucleoside tetraphosphatases (EC 3.6.1.17) from
      human and the narrow-leafed lupin. ppCH2ppA and pCH2pppA, inhibited the human
      enzyme with Ki values of 1.6 and 2.3 nm, respectively, and the lupin enzyme with
      Ki values of 30 and 34 nm, respectively. They are thereby identified as being the
      strongest inhibitors ever reported for the (asymmetrical) dinucleoside
      tetraphosphatases. The three analogues having two halo/methylene bridges are much
      less potent inhibitors for these enzymes. These novel nucleotides should prove
      valuable tools for further studies on the cellular functions of mono- and
      dinucleoside polyphosphates and on the enzymes involved in their metabolism.

PMID- 16441670
TI  - Cell type-specific transgene expression of the prion protein in Xenopus
      intermediate pituitary cells.
AB  - The cellular form of prion protein (PrPC) is anchored to the plasma membrane of
      the cell and expressed in most tissues, but predominantly in the brain, including
      in the pituitary gland. Thus far, the biosynthesis of PrPC has been studied only
      in cultured (transfected) tumour cell lines and not in primary cells. Here, we
      investigated the intracellular fate of PrPCin vivo by using the neuroendocrine
      intermediate pituitary melanotrope cells of the South-African claw-toed frog
      Xenopus laevis as a model system. These cells are involved in background
      adaptation of the animal and produce high levels of its major secretory cargo
      proopiomelanocortin (POMC) when the animal is black-adapted. The technique of
      stable Xenopus transgenesis in combination with the POMC gene promoter was used
      as a tool to express Xenopus PrPC amino-terminally tagged with the green
      fluorescent protein (GFP-PrPC) specifically in the melanotrope cells. The GFP
      PrPC fusion protein was expressed from stage-25 tadpoles onwards to juvenile
      frogs, the expression was induced on a black background and the fusion protein
      was subcellularly located mainly in the Golgi apparatus and at the plasma
      membrane. Pulse-chase metabolic cell labelling studies revealed that GFP-PrPC was
      initially synthesized as a 45-kDa protein that was subsequently stepwise
      glycosylated to 48-, 51-, and eventually 55-kDa forms. Furthermore, we revealed
      that the mature 55-kDa GFP-PrPC protein was sulfated, anchored to the plasma
      membrane and cleaved to a 33-kDa product. Despite the high levels of transgene
      expression, the subcellular structures as well as POMC synthesis and processing,
      and the secretion of POMC-derived products remained unaffected in the transgenic
      melanotrope cells. Hence, we studied PrPC in a neuroendocrine cell and in a well
      defined physiological context.

PMID- 16441669
TI  - Molecular mechanisms regulating molting in a crustacean.
AB  - Crustacean growth and development is characterized by periodic shedding (ecdysis)
      and replacement of the rigid exoskeleton. Secretions of the X-organ sinus gland
      complex control the cellular events that lead to growth and molting. Western blot
      and ELISA results showed a progressive increase in growth arrest-specific protein
      (Gas7) from early postmolt stage to a maximum at late postmolt stage.
      Phosphorylation of ERK2, a downstream signaling protein, was also identified in
      the subsequent stages. ERK2 phosphorylation resulted in the expression of molt
      inhibiting hormone (MIH). Specific ERK inhibitors (PD98059 and UO126) exhibited
      the ability to reduce the molting duration of Fenneropenaeus indicus from 12-14
      days to 7-8 days, suggesting that the ERK1/2 signaling pathway is responsible for
      the expression of MIH, which controls the molt cycle. We have identified the
      stage-specific expression of Gas7 (approximately 48 kDa) in the X-organ sinus
      gland complex of eyestalk which is involved in the downstream signaling of the
      ERK1/2 pathway regulating the expression of MIH during the molt cycle of the
      white shrimp, F. indicus. These are the first data showing an association between
      the Gas7 signal-transduction process and regulation of the molt cycle and
      provides an alternative molecular intervention mechanism to the traditional
      eyestalk ablation in crustaceans.

PMID- 16441671
TI  - Detergent-resistant membranes are platforms for actinoporin pore-forming activity
      on intact cells.
AB  - Sticholysin II is a pore-forming toxin produced by the sea anemone Stichodactyla
      helianthus. We studied its cytolytic activity on COS-7 cells. Fluorescence
      spectroscopy and flow cytometry revealed that the toxin permeabilizes cells to
      propidium cations in a dose-dependent and time-dependent manner. This
      permeabilization is impaired by preincubation of cells with cyclodextrin.
      Isolation of detergent-resistant cellular membranes showed that sticholysin II
      colocalizes with caveolin-1 in fractions corresponding to raft-like domains. The
      interaction of sticholysin II with such domains is only lipid dependent as it
      also occurs in the absence of any other membrane-associated protein. Toxin
      binding to raft-like lipid vesicles inhibited cell permeabilization. The results
      suggest that sticholysin II promotes pore formation in COS-7 cells through
      interaction with membrane domains which behave like cellular rafts.

PMID- 16441672
TI  - Life is never the same: childhood cancer narratives.
AB  - No longer considered an inevitably fatal disease, childhood cancer nonetheless
      presents many challenges for children and families. Developing an understanding
      of the impact that childhood cancer has on the lives of children and their
      families is essential to being able to provide comprehensive and sensitive care
      to them. Hence, a longitudinal qualitative study guided by the philosophy of
      interpretive interactionism was conducted to arrive at an understanding of what
      it was like to experience childhood cancer and its symptom course from the
      perspectives of children and their families. Thirty-nine children with a variety
      of cancer diagnoses and their families participated. Data collection methods
      included formal and informal interviewing and participant observation. As part of
      the data analysis process, narratives of the children's and families' experiences
      were created that provided direction in comprehending how childhood cancer and
      its symptoms affected children and their families. The narratives helped to
      illuminate the reality of the children's and families' experiences. This paper
      focuses on describing the core narrative lived by the children and their
      families. The core narrative, 'life is never the same', represents the extent to
      which cancer truly affected the children's and their families' life stories.
      Three narratives embedded in the core narrative are also described: (1) losses:
      shared and unique; (2) moving forward, moving on; and (3) it is never over with .
      . . always a waiting game. The narratives in this paper are valuable to those
      healthcare professionals who seek to develop a greater understanding of how
      childhood cancer and its symptoms impacts on children's and families' ways of
      being in the world.

PMID- 16441673
TI  - Complementary and alternative medicine use in patients with head and neck cancers
      in Europe.
AB  - The aim of the present study was to examine the patterns of complementary and
      alternative medicine (CAM) use in a sample of head and neck cancer patients,
      forming part of a larger study. A cross-sectional survey design was used
      collecting data through a descriptive 27-item questionnaire in nine countries in
      Europe. The participants were 75 patients with head and neck cancers. The
      prevalence rate of CAM use was 22.7%. The most common therapies used were herbal
      medicine (47%), medicinal teas (23.5%), use of vitamins/minerals (11.8%) and
      visualization (11.8%). Use of CAM dramatically increased after the diagnosis with
      cancer (i.e. eightfold increase in the use of herbs). A profile of CAM users was
      not evident in this sample. Patients used CAM for a variety of reasons together,
      with counteracting the ill effects from cancer and its treatment being the most
      common one. Information about CAM was obtained mostly from friends and family. As
      one in five head and neck cancer patients use CAM it is important that clinicians
      explore practices with their patients, improve communication about CAM with them
      and assist those who want to use CAM in using appropriate and safe therapies.

PMID- 16441674
TI  - The group matters: an explorative study of group cohesion and quality of life in
      cancer patients participating in physical exercise intervention during treatment.
AB  - A series of studies have shown that physical activity improves cancer patients
      functional capacity and quality of life (QOL). Few of these studies have included
      physical exercise carried out in a group setting. However, patient's experience
      with the in-group processes remains unexplored. This study investigated group
      cohesion and changes in QOL in 55 cancer patients undergoing chemotherapy who
      participated in a 9 h weekly group exercise programme for 6 weeks. The study used
      a method triangulation component design. Seven qualitative group interviews were
      conducted post-intervention. QOL (SF-36; EORTC QLQ-C30) was assessed at baseline
      and after Week 6. The interviews revealed that group cohesion was an interim goal
      aimed to maximize peak performance potential by patients. Group cohesion was
      characterized by a special 'esprit de corps' and enabled the group members to
      feel like sport teams. The programme made purposeful togetherness possible while
      allowing the patients an opportunity to let their illness fade into the
      background. Questionnaire data showed significant improvements in mental health,
      social and emotional functioning. This study identified a conceptualization of
      group cohesion that forms a valuable basis for a larger randomized controlled
      trial to conclude whether the observed changes are a result of this specific
      intervention.

PMID- 16441675
TI  - Exercise preferences among a population-based sample of non-Hodgkin's lymphoma
      survivors.
AB  - In the present study, we examined the exercise preferences of a population-based
      sample of non-Hodgkin's lymphoma (NHL) survivors. A secondary purpose was to
      explore the association between various demographic, medical, and exercise
      behaviour variables and elicited exercise preferences. Using a retrospective
      survey design, 431 NHL survivors residing in Alberta, Canada completed a mailed
      questionnaire designed to assess exercise preferences, past exercise behaviour,
      and various demographic variables. Overall, 77% of participants preferred or
      maybe preferred to receive exercise counselling at some point after their NHL
      diagnosis. An overwhelming majority indicated that they would possibly be
      interested (81%) and able (85%) to participate in an exercise programme designed
      for NHL survivors. The majority of participants (55%) listed walking as their
      preferred choice of exercise. Logistic regression analyses indicated that NHL
      survivors' exercise preferences were influenced by body mass index (BMI),
      exercise behaviour, and gender. Eliciting exercise preferences from the
      population in question yields important information for cancer care professionals
      designing exercise programmes for NHL survivors. Furthermore, tailoring exercise
      programmes to the preferences of NHL survivors may be one method to potentially
      enhance exercise adherence in this population both inside and outside of clinical
      trials.

PMID- 16441676
TI  - Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy.
AB  - Invasive fungal infections are fatal complications for patients on chemotherapy,
      and antifungal prophylactic treatment has been commonly recommended. Because its
      clinical and economic impact is not well known, we evaluated cost-effectiveness
      of anti-fungal treatment for patients who were neutropoenic as a result of
      chemotherapy. We constructed a hypothetical cohort of 40-year-old patients with
      acute myelogenic leukemia to evaluate years of life survived (YLS), costs (US$),
      and incremental cost-effectiveness ratio (US$/YLS). The following treatment
      strategies for fungal infections were compared: (1) prophylactic fluconazole
      strategy: oral fluconazole administration concurrently with chemotherapy; (2)
      empirical amphotericin B strategy: empirical intravenous amphotericin B
      administration at the point where fever is detected; and (3) no prophylaxis
      strategy: intravenous micafangin administration at the point where fungal
      infections is diagnosed. Baseline analyses showed that prophylactic fluconazole
      strategy involved higher costs but also longer YLSs (25,900 US$ and 24.08 YLS).
      The incremental cost-effectiveness ratio of prophylactic fluconazole strategy was
      625 US$/YLS compared to no prophylaxis strategy, and 652 US$/YLS compared to
      empirical amphotericin B strategy. Baseline result was found to be robust through
      sensitivity analyses. Our study showed that concurrent administration of oral
      fluconazole during induction chemotherapy appears to ensure clinical benefits
      together with acceptable cost-effectiveness.

PMID- 16441677
TI  - Positive feelings among terminally ill cancer patients.
AB  - For a realistic perspective on what it is like to have cancer and be in the last
      months of life, it is necessary to also study the positive feelings people may
      still experience. We set out to describe positive feelings experienced by
      terminally ill patients. The Depression Adjective Checklist was completed by 96
      cancer patients with an estimated life expectancy of less than 3 months. On
      average patients endorsed 30% (3.6/12) of the positive mood items, and 25%
      (5.4/22) of the negative mood items. The larger part of terminally ill cancer
      patients with an estimated life expectancy of less than 3 months reported one or
      more positive mood states. A positive mood state such as 'being interested' was
      endorsed by more than half (65%) of the patients, other positive feelings were
      endorsed by a substantial proportion of patients, for example: 38% of patients
      endorsed feeling 'jovial' and 35% reported being 'optimistic'. Although having
      incurable cancer often leads to feelings of depression, mood is variable and many
      patients experience at least some positive feelings.

PMID- 16441678
TI  - Cancer patients' opinions concerning post-treatment follow-up.
AB  - Cancer is one of the most serious and widespread diseases known. Statistics show
      that of about 4 million Norwegians, every third person will be afflicted by some
      form of cancer during one's lifetime. Around 20,000 Norwegians receive this
      diagnosis yearly. People who have cancer often indicate that they feel neglected
      after they have received the diagnosis and perhaps hospital treatment. This
      article describes a survey in which a questionnaire was employed to map the
      services and post-treatment care offered by county health services to cancer
      patients. The form was sent to 199 persons between the age of 18 and 70, all of
      whom had been diagnosed with cancer from 6 months to 3 years earlier. The
      questionnaire was addressed directly to the patients, and distributed by mail.
      Both the Regional Medical Ethics Committee and the Information Protection Agency
      gave their approval with respect to how the patients and control group were
      selected, and to the general procedures used in the project. Eighty-six
      questionnaires were filled out and returned, giving a response rate of 43%. Of
      those who returned the form, 44 were women and 42 were men. Their average age was
      57 years. The majority of those who responded to the questionnaire had been
      diagnosed for cancer at least 2 years earlier. Of the responding patients, 49
      persons said that they had been declared cured, 25 answered that they were still
      ill and 12 did not reply to this question. The survey results indicate that few
      services or training programmes had been offered to the patients after their
      treatment was completed. This conclusion is corroborated by a questionnaire
      filled out by doctors and administrative leaders in the home-nursing programme as
      part of the same project. The cancer patients had not been clearly informed
      whether they should contact the hospital or the health services in their home
      county if they needed assistance. The patients also expressed a desire for better
      information and a more systematic post-treatment programme, as well as clear
      guidelines delineating the specific areas of responsibility assigned to hospitals
      and the local public health services.

PMID- 16441679
TI  - Palliative care treatment patterns and associated costs of healthcare resource
      use for specific advanced cancer patients in the UK.
AB  - The purpose of this paper is to identify the treatment patterns and corresponding
      costs of healthcare resource use associated with palliative care for different
      types of advanced cancer patients, from the time they started strong opioid
      treatment until death. This was a modelling study performed from the perspective
      of the UK's National Health Service (NHS). A data set was created comprising 547
      patients in the DIN-Link database who had a Read code for malignant neoplasms
      with a specific tumour-type diagnosis and who received their first strong opioid
      between 1 January 1998 and 30 September 2000 and died during that period.
      Palliative care-related resource utilization data were obtained from the DIN-Link
      database. Unit costs at 2000/2001 prices were applied to the resource use
      estimates to determine the mean cost of palliative care from the start of
      treatment until death. There were significant differences in age between patients
      with different cancer types and in patients' survival from diagnosis, time to the
      start of palliative care and duration of palliative care. The mean duration from
      cancer diagnosis to the start of strong opioid treatment ranged from 0.7 to 5.4
      years in patients with lung and breast cancer respectively. Moreover, the length
      of palliative care ranged from 180 to 372 days in patients with these cancer
      types respectively. There were also statistically significant differences in
      resource use between patients with different cancer types, but this reflected, in
      part, the varying durations of palliative care. Nevertheless, there were also
      differences in the monthly number of primary care visits reflecting the different
      number of monthly prescriptions. There was no apparent relationship between the
      length and corresponding cost of palliative care which ranged from 1816 pounds
      sterling for colon cancer to 4789 pounds sterling for ovarian cancer.
      Additionally, on average, only a third of all patients also received 4-hourly
      morphine as part of their initial strong opioid treatment. The total cost of
      palliative care varied between cancer type and reflects, at least in part, the
      distinct clinical features associated with different tumours and the varying
      lengths of survival following the start of strong opioid treatment. Nevertheless,
      no apparent relationship was found between length of palliative care and
      corresponding costs. This analysis provides data on palliative care resource use
      for a variety of cancers and could provide useful input when planning local
      healthcare strategies and building service commissioning models.

PMID- 16441680
TI  - Antibiotic use during the last days of life in cancer patients.
AB  - The purpose of this study is to document infection and to better understand
      current practice relating to antibiotic use and its effect in terminal cancer
      patients. We retrospectively reviewed patients with terminal stage cancer who
      were admitted to Seoul National University Boramae Hospital for symptom control
      only, and who finally died between March 2003 and April 2004. A total of 141
      patients were enrolled. Mean duration from admission to death was 31.2 days. A
      total of 104 patients (75.2%) experienced a febrile episode, and physicians
      considered 113 patients (80.1%) developed a clinical infection. Total 119
      patients (84.4%) received antibiotics. For 90 patients (63.8%), antibiotics were
      used until the day of death. After using antibiotics, 48% of fevers were
      controlled, and 31% of organism-proven cases were resolved. Symptomatic
      improvement of infection was achieved in 18 patients (15.1%), but 66 patients
      (55.4%) showed no improvement. Improved leucocytosis was achieved by 17% and C
      Reactive Protein elevation by 29%. In conclusion, our study reveals a high rate
      of infection and a high rate of antibiotic prescription during the last month of
      life in cancer patients. But symptomatic improvement was not achieved in more
      than half of the patients. Further study should be undertaken to clarify the
      benefit of antibiotics in terminal stage cancer patients.

PMID- 16441681
TI  - Distress and coping in cancer patients: feasibility of the Icelandic version of
      BSI 18 and the WOC-CA questionnaires.
AB  - The aim of this study was to test the feasibility of two instruments within an
      Icelandic context, the Brief Symptom Inventory 18 (BSI 18) and the Ways of Coping
      Inventory--Cancer Version (WOC-CA) with specific focus on gender and type of
      treatment and coping techniques among cancer patients during time of treatment.
      The sample consisted of 40 cancer patients in three oncology outpatient clinics
      in Iceland, 53% were women and 47% men. The majority of the participants belonged
      to the age group 51-70. Cronbach alpha, means, confidence intervals and standard
      deviations were used for analysis as well as Mann-Whitney U-test for testing
      differences between genders in relation to psychological distress and coping.
      Anxiety was the factor causing the greatest distress, mainly reported by patients
      receiving chemotherapy. More women experienced depression than men, women
      (18.4%), men (8.3%). Distancing was the most frequently reported coping strategy,
      and men seemed to focus on the positive side more often than women did (P <
      0.01). Although the results should be approached with caution, as the sample size
      was small, they do provide support for the strength of the measurements. Also the
      findings indicate that gender differences should be taken into account.

PMID- 16441682
TI  - Headache characteristics and brain metastases prediction in cancer patients.
AB  - The aim of this study was to evaluate the headache and other neurological
      symptoms and signs as guide predictors for the occurrence of brain metastases in
      cancer patients. We prospectively studied 54 cancer patients with newly appeared
      headache or with a change in the pattern of an existing headache during the
      recent months. All patients completed a questionnaire regarding headache's
      clinical characteristics and existence of accompanying symptoms. They also
      underwent a detailed neurological, ophthalmologic examination and brain
      neuroimaging investigation. Brain metastases were diagnosed in 29 patients.
      Univariate regression analysis showed an association between occurrence of brain
      metastases and nine clinical symptoms or signs. Multivariate regression analyses
      emerged only four of them as significant independent predictors. These were:
      bilateral frontal-temporal headache, more pronounced on the side of metastasis in
      cases of single metastases, with duration > or =8 weeks, pulsating quality and
      moderate to severe intensity (OR: 11.9; 95% CI. 2.52-56.1), emesis (OR: 10.2; 95%
      CI. 2.1-55.8), gait instability (OR: 7.4; 95% CI. 1.75-33.9) and extensor plantar
      response (OR: 12.1; 95% CI. 2.2-120.7). In conclusion, all cancer patients who
      manifest the above independent clinical predictors should be highly suspected for
      appearance of brain metastases and therefore should be thoroughly investigated.

PMID- 16441684
TI  - What do you think of midwife-led units?

PMID- 16441685
TI  - How honest can a medical journal be?

PMID- 16441686
TI  - The developmental origins of adult disease (Barker) hypothesis.
AB  - Many studies have provided evidence for the hypothesis that size at birth is
      related to the risk of developing disease in later life. In particular, links are
      well established between reduced birthweight and increased risk of coronary heart
      disease, diabetes, hypertension and stroke in adulthood. These relationships are
      modified by patterns of postnatal growth. The most widely accepted mechanisms
      thought to underlie these relationships are those of fetal programming by
      nutritional stimuli or excess fetal glucocorticoid exposure. It is suggested that
      the fetus makes physiological adaptations in response to changes in its
      environment to prepare itself for postnatal life. These changes may include
      epigenetic modification of gene expression. Less clear at this time are the
      relevance of fetal programming phenomena to twins and preterm babies, and whether
      any of these effects can be reversed after birth. Much current active research in
      this field will be of direct relevance to future obstetric practice.

PMID- 16441687
TI  - Fertility preservation in female oncology patients.
AB  - Survival rates for patients treated for the majority of childhood and young adult
      cancers have improved dramatically in recent years. Despite the high probability
      of survival, and often good quality of life in female survivors, until recently
      the concept of fertility preservation has not been seen to be an important
      component of the overall management of these patients. Over the last few years,
      various protection and preservation strategies have been developed, which may
      address potential reproductive concerns. Gametes or embryos may be frozen prior
      to potentially gonadotoxic cancer therapy, and ovarian tissue may be frozen and
      stored, with several pregnancies described after subsequent grafting. There is
      also increasing interest in the possibility of ovarian protection using
      gonadotrophin-releasing hormone analogues during chemotherapy, despite the lack
      of randomised controlled trials. Additionally, there are reports of novel
      protective strategies, including therapeutic alteration or manipulation of the
      sphingomyelin pathways. This review summarises methods of fertility protection
      and preservation currently available, as well as the emergence of promising new
      strategies.

PMID- 16441688
TI  - Adverse outcome of pregnancy following air travel: a myth or a concern?
AB  - OBJECTIVE: To assess whether air travel elevates the risk of adverse pregnancy
      outcomes in essentially healthy women with single non-anomalous fetuses at a
      gestational age greater than 20 weeks. METHODS: A retrospective analysis of air
      travel during the current pregnancy and pregnancy outcome was undertaken in 992
      women admitted for delivery over a 12-month period. The study group of 546 (55%)
      women, of whom 57% were primigravidae, travelled at least once during pregnancy,
      and were compared with a control group of 447 women (45%), of whom 54% were
      primigravidae, who did not travel by air. RESULTS: The primigravidae in the study
      group showed an increased risk of preterm birth, and this risk was statistically
      significant between the gestations of 34 and 37 weeks (adjusted odds ratio 1.5,
      95% confidence intervals 1.2, 1.8); this risk remained elevated after adjustment
      for covariates. These women's pregnancies were appreciably shorter than those of
      primigravidae who did not fly (36.1 +/- 0.8 vs. 39.2 +/- 2.1 weeks) and their
      babies had lower birthweights (2684 +/- 481 vs. 3481 +/- 703 g). and were more
      likely to be admitted to the neonatal intensive care unit. This group of air
      travellers is unusual for the uncommonly long and frequent duration of air
      travel, which is not routinely undertaken in most parts of the world. There were
      no thromboembolic events complicating any pregnancies. CONCLUSIONS: Primigravid
      women who travel by air appear to be at higher risk for preterm birth.
      Multicentre large studies are required to confirm or repute these findings.

PMID- 16441689
TI  - Mullerian dysgenesis: a review of recent outcomes at Royal Hospital for Women.
AB  - BACKGROUND: Mullerian dysgenesis occurs in approximately 1 in 5000 live-born
      females. There have been many methods described for creation of a functionally
      useful vagina in cases of Mullerian dysgenesis. Given the number of available
      methods and the infrequency of the condition, outcome data can be difficult to
      obtain. AIM: To perform a retrospective review of presentation, treatment and
      outcomes in cases of Mullerian dysgenesis seen at the adolescent gynaecology unit
      at the Royal Hospital for Women, Sydney. METHODS: Thirty women with Mullerian
      dysgenesis were identified between January 2000 and December 2004. Of these, 23
      had Mullerian agenesis and seven had partial vaginal agenesis. As this audit and
      review conform with the standards established by the National Health and Medical
      Research Council for ethical quality review, ethics approval was not sought.
      RESULTS: Dilator therapy under the guidance of a trained clinical nurse educator
      was successful in creating a functionally useful vagina and was well tolerated in
      all cases of Mullerian agenesis. Patients suffering from segmental vaginal
      agenesis all had surgical creation of a neovagina with the aid of an amnion
      vaginoplasty. All patients who were referred following surgical drainage of their
      haematocolpos outside the unit became infected and needed to undergo further
      surgery prior to creation of a neovagina. Fibrotic vaginal bands developed only
      in these patients. CONCLUSION: The outcomes reinforce the TASPAG guidelines of
      management for Mullerian dysgenesis, which suggest that dilators are generally
      effective in creating a functionally useful vagina, and if surgery is required,
      the primary operation should be definitive and performed by well-trained experts.

PMID- 16441690
TI  - Placental assessment: simple techniques to enhance best practice.
AB  - BACKGROUND: The placenta provides a 'diary' of the pregnancy. The information
      provided from pathological assessment of the placenta may provide important
      clinical information for both the mother and the neonate. AIMS: To develop tools
      to ensure histopathological assessment of appropriate placentas and uniform
      provision of clinical history to pathologists to enable clinicopathological
      assessment. METHODS: A placenta information form was devised that included the
      following clinical criteria: gestational age, prolonged rupture of membranes at
      term, suspected maternal/fetal bacterial or viral infection, swabs taken for
      culture, intrauterine growth restriction, perinatal death, pre-eclampsia,
      essential hypertension, diabetes, placenta praevia, multiple pregnancy and
      cytogenetics. A table was introduced into the midwifery placenta policy
      indicating clinical criteria for microbiology, histopathological or cytogenetic
      assessment. A colourful reminder poster was designed and placed in the delivery
      suite and education sessions were provided. Six-month review periods were
      performed prior to and following the two interventions. RESULTS: The number of
      placentas submitted for histopathological examination (and meeting the inclusion
      criteria) increased from 41 (120/296) to 61% (161/266) following the initial
      interventions and to 82% (262/319) with the introduction of the reminder poster
      and education sessions. Clinically relevant placental pathology was found in 55
      (64%) of cases in these time intervals. Comprehensive clinical history on the
      pathology report improved from 45 to 98% over the assessment time. CONCLUSIONS:
      Valuable information on a pregnancy can be provided by ensuring histopathological
      examination of appropriate placentas with the simple introduction of placental
      information sheets, updated midwifery policy, education sessions and a colourful
      reminder poster.

PMID- 16441691
TI  - Effect of BCG vaccine on peritoneal endometriotic implants in a rat model of
      endometriosis.
AB  - OBJECTIVE: To investigate the effect of Bacillus Calmette-Guerin (BCG) vaccine on
      peritoneal implantation of endometrial tissue in rats. METHODS: Forty sexually
      mature virgin Wistar albino rats weighing 190-200 g were randomly assigned
      (double blind) to two groups. The rats in the first group were vaccinated with
      0.1 mL BCG and those in the second group were injected with 0.1 mL saline into
      the tail, intracutaneously. All the rats underwent median laparotomy after 4
      weeks of vaccination or injection. The right uterine horn was excised, and the
      two samples of endometrial tissue dissected from myometrium were implanted on
      each side of peritoneum at the 2 cm lateral line of the median laparotomy
      incision. The implanted peritoneal segments were excised after 8 weeks of
      laparotomy. The tissue samples were accepted, histologically, as endometriosis
      when both glands and stroma of endometrial tissue were seen in sections. RESULTS:
      Thirty-six implants from the study group and 34 implants from the control group
      were obtained. Ten and 23 implants were accepted as endometriosis in the study
      and control group, respectively. The number of endometriotic foci were
      significantly lower in the study group than in the control group (P = 0.01).
      CONCLUSIONS: Stimulation of the cellular immune response with BCG vaccine could
      exert an inhibitory effect on ectopic endometriotic implants.

PMID- 16441692
TI  - Biocompatible properties of surgical mesh using an animal model.
AB  - AIM: To study the biocompatibility of surgical meshes for use in pelvic
      reconstructive surgery using an animal model. METHODS: Eight different types of
      mesh: Atrium, Dexon, Gynemesh, IVS tape, Prolene, SPARC tape, TVT tape and Vypro
      II, were implanted into the abdominal walls of rats for 3 months' duration.
      Explanted meshes were assessed, using light microscopy, for parameters of
      rejection and incorporation. RESULTS: Type 1 (Atrium, Gynemesh, Prolene, SPARC
      and TVT) and type 3 (Vypro II, Dexon and IVS) meshes demonstrated different
      biocompatible properties. Inflammatory cellular response and fibrosis at the
      interface of mesh and host tissue was most marked with Vypro II and IVS. All type
      1 meshes displayed similar cellular responses despite markedly different mesh
      architecture. CONCLUSIONS: The inflammatory response and fibrous reaction in the
      non-absorbable type 3 meshes tested (IVS and Vypro II) was more marked than the
      type 1 meshes. The increased inflammatory and fibrotic response may be because of
      the multifilamentous polypropylene components of these meshes. Material and
      filament composition of mesh is the main factor in determining cellular response.

PMID- 16441693
TI  - Treatment decisions: a qualitative study with women with gynaecological cancer.
AB  - This qualitative study investigated women's participation in decisions regarding
      treatment of gynaecological cancer. Thirty women, receiving health care in two
      tertiary hospitals in Australia, were interviewed face-to-face. For women with
      gynaecological cancer, the most influential factors in treatment decisions are
      still the surgeon's recommendation and fear of dying from cancer.

PMID- 16441694
TI  - Treatment of rectovaginal fistula: a 5-year review.
AB  - This paper presents a chart review of 17 patients who had been treated for
      rectovaginal fistula (RVF) from 1996 to 2000. In most cases (13; 76.5%), the
      fistula was the result of post-surgical complications. Following vaginal mucosa
      advancement flap repair or repair after conversion to a fourth-degree perineal
      laceration, 16 (94%) of the rectovaginal fistulae (during the first attempted
      repair or after failed treatment) were successfully treated. In all patients but
      one, faecal diversion was avoided. In two patients, fistulography was both a
      diagnostic procedure and the method of treatment.

PMID- 16441695
TI  - Adnexal masses in pregnancy: a 5-year review.
AB  - A retrospective analysis of all pregnant women who had an adnexal mass surgically
      resected at the Government Medical College and Hospital, Chandigarh, over a 5
      year period found an incidence of 20 in 16,260 deliveries during the study
      period. The most frequent complication was torsion (25% of the cases) and the
      majority of cases occurred in the first trimester of pregnancy. Two of the women
      had malignant ovarian tumours. There was no difference in gestational age at
      delivery or birth weight in patients undergoing emergency surgery versus elective
      surgery.

PMID- 16441696
TI  - Prenatal detection of birth defects in a Malaysian population: estimation of the
      influence of termination of pregnancy on birth prevalence in a developing
      country.
AB  - We studied 253 women with a pregnancy complicated by a birth defect and 506
      controls to determine the frequency and type of prenatal tests and the types of
      defects detected antenatally. Most women had at least one ultrasound examination,
      but the frequency of other screening tests was low. Only 38 (15%) of defects were
      detected antenatally (37 by ultrasound). Birth prevalence is unlikely to be
      affected by pregnancy termination.

PMID- 16441697
TI  - Sclerosing encapsulating peritonitis and methotrexate.

PMID- 16441698
TI  - Incarcerated uterine procidentia and vesical calculi: a case report.

PMID- 16441699
TI  - Uterine rhabdomyosarcoma presenting as acute inversion in an adolescent.

PMID- 16441701
TI  - Management of a chronic wound secondary to pyoderma gangrenosum following
      uncomplicated lower segment Caesarean section incision.

PMID- 16441700
TI  - An unusual presentation of basaloid vaginal intraepithelial neoplasia in a young
      infertile woman.

PMID- 16441702
TI  - Re: An alternative cost-effectiveness analysis of ThinPrep in the Australian
      setting.

PMID- 16441703
TI  - Re: Reasons for requesting pregnancy termination and attitude of women when
      request is being refused: a face-to-face interview study.

PMID- 16441704
TI  - Re: Bilateral ureterohydronephrosis during twin pregnancy.

PMID- 16441705
TI  - Re: Postoperative analgesic requirements--total laparoscopic hysterectomy versus
      vaginal hysterectomy.

PMID- 16441706
TI  - Re: Liquid-based cytology for cervical screening.

PMID- 16441708
TI  - Re: Use of the Atad catheter for the induction of labour in women who have had a
      previous Caesarean section: a case series.

PMID- 16441710
TI  - Myocardial contractility and cardiac filling measured by impedance cardiography
      in patients with nitroglycerine-induced vasovagal syncope.
AB  - OBJECTIVE: Increased myocardial contractility and inadequate cardiac filling
      leading to activation of the Bezold-Jarisch reflex were proposed as possible
      triggering mechanisms of vasovagal syncope (VVS). In the present study
      noninvasive hemodynamic measurements were performed in order to examine the role
      of myocardial contractility and cardiac filling in pathogenesis of VVS. METHODS:
      Hemodynamic parameters were measured during head-up tilt test (HUT) by impedance
      cardiography in 46 patients with unexplained syncope. Myocardial contractility
      was measured as index of contractility (IC), acceleration index (ACI), and
      ejection fraction (EF). Afterload was measured as systemic vascular resistance
      index (SVRI) and preload was expressed as end-diastolic index (EDI). Serial
      measurements were done 1 minute before HUT, during HUT at 1-minute intervals, and
      1 minute after completion of HUT. RESULTS: HUT was positive in 30 patients (10
      men, 20 women, mean age 36 +/- 16 years) and negative in 16 patients (8 men, 8
      women, mean age 31 +/- 14 years). No significant differences were observed
      between HUT(+) and HUT(-) groups in hemodynamic parameters at supine rest and
      during HUT until the development of syncope. SVRI was lower in HUT(+) than in
      HUT(-) group at syncope (122.7 + 66.3 vs 185.6 + 51.4 dyn sec cm(-5)/m2, P =
      0.002) and after syncope (117.0 + 61.1 vs 198.0 + 95.7 dyn sec cm(-5)/m2, P =
      0.007). ACI, IC, EF, and EDI did not differ between groups at syncope. After
      syncope EF was higher in HUT(+) group compared to HUT(-) group (59.2 + 6.1 vs
      52.7 + 9.4%, P = 0.02). CONCLUSION: The role of increased myocardial
      contractility and decreased cardiac filling is not confirmed in the present
      study.

PMID- 16441711
TI  - Suboptimal glycemic control, independently of QT interval duration, is associated
      with increased risk of ventricular arrhythmias in a high-risk population.
AB  - BACKGROUND: Although cardiovascular disease is the leading cause of mortality in
      diabetic patients, little is known about the impact of glycemic control on
      ventricular tachycardia (VT). OBJECTIVE: To investigate whether hemoglobin A1c
      (HbA1c) is associated with increased incidence of VT. METHODS: A retrospective
      study of 336 implantable cardioverter-defibrillator patients (both diabetes
      mellitus (DM) and non-DM) was conducted. RESULTS: HbA1c levels between 8% and 10%
      had a significant association with spontaneous VT, but not with QT/QTc.
      CONCLUSIONS: Glycemic index is a significant predictor of spontaneous VT,
      independently of QT interval. Optimal glycemic control may help reduce occurrence
      of VT and sudden cardiac death in high-risk DM patients.

PMID- 16441712
TI  - Electrical space-time abnormalities of ventricular depolarization in patients
      with Brugada syndrome and patients with complete right-bundle branch blocks
      studied by magnetocardiography.
AB  - BACKGROUND: Both ventricular depolarization abnormalities (QRS complex) and
      repolarization ones (ST/T) are still controversial in literature. The objective
      of this study was to clarify the space-time variations that occur in patients
      carriers of Brugada syndrome using Magnetocardiography and also compare them with
      cases of complete right-bundle branch block (CRBBB) and individuals without any
      dromotropic disorder (control group). METHODS AND RESULTS: Magnetocardiograms
      (MCGs) of Brugada syndrome patients (n = 16), CRBBB patients (n = 14), and
      members of a control group (n = 46) at rest were recorded. The MCGs were used to
      produce a whole-heart electrical-activation diagram (W-HEAD), which can visualize
      the spatial time-variant activation in the whole heart. In the W-HEAD pattern,
      three activations were located in the left ventricle, and CRBBB patients had a
      wide peak with about 65-ms delay on the right anterior side. While the Brugada
      syndrome pattern has a posteromedian left-ventricle excitation, that is half the
      amplitude that occurs in CRBBB patients, the electrical conduction rate to the
      posterosuperior septum area was low. CONCLUSIONS: The W-HEAD data made it
      possible to visualize space-time depolarization abnormalities. These findings
      suggest that the electrical conduction rate to the posterosuperior septum area in
      Brugada syndrome cases is low, and this low activation may be a feature of
      typical Brugada syndrome.

PMID- 16441713
TI  - Frequency of spontaneous and inducible atrioventricular nodal reentry tachycardia
      in patients with idiopathic outflow tract ventricular arrhythmias.
AB  - OBJECTIVES: We sought to assess the frequency of spontaneous or inducible
      atrioventricular nodal reentry tachycardia (AVNRT) in patients referred for
      radiofrequency ablation (RFA) of idiopathic outflow tract ventricular
      arrhythmias. BACKGROUND: In patients with no obvious heart disease, AVNRT and
      outflow tract ventricular tachycardia (VT) are the most frequently encountered
      supraventricular and ventricular tachycardias, respectively. An increased
      coexistence of the two arrhythmias has been recently suggested. METHODS: In 68
      consecutive patients referred for RFA of an idiopathic ventricular outflow tract
      arrhythmia, a stimulation protocol including repeated bursts of rapid atrial
      pacing, up to triple atrial extrastimuli during sinus rhythm and rapid
      ventricular pacing was performed before and after isoproterenol infusion
      following RFA of the ventricular arrhythmia. In patients with inducible AVNRT,
      RFA of the slow pathway was performed. RESULTS: Of the 68 study patients, 17
      (25%) had either spontaneous AVNRT documented prior to RFA of the ventricular
      arrhythmia (n = 4) or inducible AVNRT at the time of RFA of the ventricular
      arrhythmia (n = 13). AVNRT was induced by atrial pacing in 15 (88%) of 17
      patients: in 3 patients without isoproterenol and in 12 patients during
      isoproterenol infusion. Uncomplicated RFA of the slow pathway was successfully
      achieved in all patients with inducible AVNRT. CONCLUSION: Spontaneous or
      inducible AVNRT is relatively common in patients with idiopathic outflow tract
      ventricular arrhythmias. Atrial stimulation, especially when performed after
      isoproterenol infusion plays a major role in AVNRT inducibility. Although we
      performed RFA of the slow pathway in patients with inducible AVNRT and no prior
      tachycardia documentation, the question whether this is mandatory remains
      unsettled.

PMID- 16441714
TI  - Antibiotic prophylaxis with a single dose of cefazolin during pacemaker
      implantation: incidence of long-term infective complications.
AB  - OBJECTIVE: Systemic and localized infections related to permanent pacemaker
      implantation are not common, but are serious and potentially life-threatening
      complications. The aims of this prospective observational study were: (1) to
      assess the safety and long-term efficacy of a simplified scheme of antibiotic
      prophylaxis, and (2) to identify the predictors of long-term infective
      complications, in patients undergoing pacemaker implantation or replacement.
      METHODS AND RESULTS: From October 1998 to July 2001, 852 patients (mean age 77.0
      +/- 9.2 years; 474 men) who underwent new permanent pacemaker implantation
      (69.6%) or pulse generator replacement (30.4%) received a mini-bag of 2 g of
      cefazolin diluted in 50 mL of saline solution, administered intravenously in 20
      minutes before the beginning of the procedure. Early (within 2 months of
      implantation) and late major and minor infective complications were recorded.
      During the earlier phase, minor complications were observed in 9 patients (1%).
      During the long-term phase of the surveillance (mean 25.6 +/- 11.0 months, range
      12-55 months) major infective complications were observed in 6 patients (0.7%).
      On multivariate analysis, no clinical or procedural variable predicted the
      occurrence of long-term infective complications. CONCLUSIONS: Our data indicate
      the safety and efficacy of a single, intravenous 2 g dose of cefazolin in
      preventing infective complications related to pacemaker implantation or
      replacement. No clinical or procedural variable predicted the occurrence of long
      term infective complications.

PMID- 16441715
TI  - Is a dual-sensor pacemaker appropriate in patients with sino-atrial disease?
      Results from the DUSISLOG study.
AB  - BACKGROUND: Rate-responsive pacemakers (PMs) are often supplied with
      accelerometer (XL) and minute ventilation (MV) sensors to provide a physiologic
      rate response according to patient needs. No information is available about the
      real benefit of dual-sensor rate-responsive pacing on the daily life of patients.
      METHODS: DUSISLOG (Dual Sensor vs Single Sensor comparison using patient activity
      LOGbook) is a two-arm prospective, randomized, multicenter study that enrolled
      105 patients who received a rate-responsive PM (Insignia), Guidant Corp.). After
      1 month of DDD pacing at 60 ppm lower rate, a single sensor (XL or MV,
      randomized) was activated for 3 months at the manufacturer's suggested nominal
      settings, followed by a 3-month period with dual sensors optimized with automatic
      response. During the last month of each period, the following data concerning
      patient physical activity were retrieved from PM diagnostics (Activity Log): mean
      percentage of physical activity, mean intensity of activity. Quality of life
      (QoL) scores and 6-minute walk test (WT) were also recorded. RESULTS: Single
      sensor rate-responsive pacing resulted in symptomatic benefit equally with XL and
      MV sensors while no additional benefit was found using dual sensor. In a subgroup
      analysis, patients (17%) with marked chronotropic incompetence and with 0% atrial
      sensing received benefits from single sensor with an additional advantage from
      sensor (QoL: +21 +/- 14% P < 0.05; WT: +17 +/- 7% P < 0.02). CONCLUSION: In most
      patients with rate-responsive devices, a single sensor is sufficient to achieve a
      satisfactory rate response. A dual sensor combination and optimization provides
      an additional benefit only in a selected population with an advanced atrial
      chronotropic disease.

PMID- 16441716
TI  - Automatic ventricular threshold measurement in children with epicardial pacing
      leads.
AB  - BACKGROUND: The aim of the study was to evaluate the safety and reliability of
      automatic ventricular pacing threshold measurement, the Medtronic Capture
      Management (CM), in children with epicardial pacing leads. CM has not been
      recommended for use with epicardial leads due to lack of pertinent data. METHODS:
      During a 2-year study period, 34 children (mean age 6.1 years, range 0 days to
      17.7 years) with epicardial leads were prospectively enrolled. The CM
      measurements were compared with in-office ventricular pacing threshold
      measurements. Thirty bipolar and five unipolar epicardial leads were assessed.
      RESULTS: CM measurements were successful and reliable in 30 out of 35 leads
      (86%). The mean threshold with CM was 1.16 V (95% CI 1.07-1.26 V), and with
      standard measurement was 1.18 V (95% CI 1.09-1.28 V), at a pulse width of 0.40
      ms. The reasons for failure were evoked response undersensing in two cases
      (5.7%), and high intrinsic rate in one case. High pacing thresholds prevented
      accurate CM measurements in two cases. CONCLUSIONS: CM automatic threshold
      measurements are consistent with standard ventricular pacing threshold
      measurements in children with epicardial leads. We recommend a period of
      monitoring CM performance before programming it to adjust output according to
      automatic threshold measurements, in order to find the patients in whom it does
      not work. The CM feature provides increased pacing safety when it measures well
      (86% of leads). A larger study is needed to prove the tendency for extending
      battery life in children with epicardial leads.

PMID- 16441717
TI  - Importance of initiation pattern of polymorphic ventricular tachycardia in
      patients with implantable cardioverter defibrillators.
AB  - BACKGROUND: Stored intracardiac electrograms (ICEGs) are helpful in understanding
      the initiation mechanisms of sustained ventricular arrhythmias and in determining
      the appropriateness of the therapy delivered by implantable cardioverter
      defibrillators (ICDs). AIM: We investigated the initiation pattern of sustained
      polymorphic ventricular tachycardia (PVT) and the features of the therapy
      delivered by ICDs. METHODS: Sixty-six patients (mean age of 67 +/- 8 years) with
      97 stored ICEGs showing PVT were evaluated. Cardiovascular diagnosis included
      coronary artery disease in 72.7% of the patients. The average left ventricular
      ejection fraction was 33+/-6%. RESULTS: Nonsudden onset episodes were more common
      than sudden onset episodes (63 episodes, 65% vs 34 episodes, 35%, P < 0.001).
      More PVT episodes were required multiple shock delivery if they had nonsudden
      onset initiation (28.6% vs 23.6%, P < 0.01). The mean shock energy delivered for
      arrhythmia termination was higher in PVT with nonsudden onset (20 +/- 4 vs 14 +/-
      5 J, P < 0.01). CONCLUSIONS: The stored ICEGs demonstrate that PVT is most often
      preceded by ventricular ectopy. To be reverted, nonsudden onset episodes require
      higher levels of shock energy and more frequently multiple shock achievements
      than sudden onset episodes.

PMID- 16441718
TI  - Power spectral analysis of heart rate variability in HIV-infected and AIDS
      patients.
AB  - BACKGROUND: In HIV-infected patients the risks for cardiovascular disease are
      multifactorial. Autonomic dysfunction has been detected in the early phase of HIV
      infection as well as in AIDS patients with advanced cardiomyopathy. METHODS:
      Forty AIDS patients receiving highly active antiretroviral therapy (HAART), 40
      HIV+ naive of HAART, and 40 control subjects were studied. Computerized analysis
      of heart rate variability was performed using an analog to digital converter. R-R
      intervals were obtained from a standard ECG, recorded in DII lead in supine rest
      and after the cold-face and tilt tests. The series of R-R intervals were assessed
      in time and frequency domains using an autoregressive algorithm. RESULTS: There
      was no difference regarding to mean values of R-R intervals and variance in
      baseline. The normalized power of the low-frequency (LF) component and the low
      frequency/high-frequency (HF) ratio (LF/HF) was significantly decreased in the
      HIV group. Responses of normalized HF and LF/HF ratio during the cold-face test
      were significantly decreased in the HIV group, as compared to the control. During
      the tilt test, a higher augmentation of normalized LF and the LF/HF ratio was
      observed in the HIV group compared with the control. The AIDS group was similar
      to the control in baseline and after cold-face and tilt tests. CONCLUSION: The
      HIV group presented in baseline conditions, a shift of cardiac sympathovagal
      balance, an exacerbated response of the LF component during the tilt test, and an
      ineffective cardiac vagal response to the cold-face test suggesting sympathetic
      and parasympathetic dysfunction. AIDS patients receiving HAART did not present
      these autonomic alterations.

PMID- 16441719
TI  - Slow pathway ablation for atrioventricular nodal reentry using a right internal
      jugular vein approach: a case series.
AB  - BACKGROUND: Inferior venous access to the right heart is not possible in some
      patients due to congenital or acquired obstruction of the inferior vena cava
      (IVC). Although right-sided electrophysiology procedures have been performed
      successfully in patients with a previously placed IVC filter by direct placement
      of catheters through the filter, an alternative approach is necessary in some
      patients. METHODS: This case series describes three patients with an IVC filter
      who underwent successful ablation of the slow pathway for typical
      atrioventricular (AV) nodal reentrant tachycardia using a superior vena cava
      (SVC) approach via the right internal jugular (IJ) vein. Two separate introducer
      sheaths were placed into the IJ vein using separate punctures. This permitted
      placement of a standard deflectable ablation catheter and an additional catheter
      in the right atrium to monitor for ventriculoatrial conduction during the
      junctional rhythm associated with ablation of the slow AV nodal pathway. RESULTS:
      Catheter ablation was successful in each patient. The number of radiofrequency
      current applications was 7, 17, and 27. There were no procedural complications
      and no patient had recurrent tachycardia during follow-up. CONCLUSIONS: Catheter
      ablation of the slow AV nodal pathway can be performed successfully and safely in
      patients with inferior venous barriers to the right heart using an SVC approach
      via the right IJ vein.

PMID- 16441720
TI  - Wide-QRS-complex tachycardia with a negative concordance pattern in the
      precordial leads: Are the ECG criteria always reliable?
AB  - We present a case of wide-complex tachycardia with negative concordance in the
      precordial leads and a qR pattern in V6, in a 42-year-old man with risk factors
      for coronary artery disease, in whom the electrocardiogram criteria were
      apparently fallible. This case highlights the key contribution of the
      electrophysiological study in rendering correct diagnosis.

PMID- 16441721
TI  - Silent lead malfunction detected only during defibrillator replacement.

PMID- 16441722
TI  - Advanced ICD troubleshooting: Part II.

PMID- 16441724
TI  - Preservation of ventricular capture by anodal stimulation after dislodgment of an
      epicardial electrode.
AB  - A 58-year-old man had a bipolar epicardial left ventricular (LV) implanted for
      cardiac resynchronization therapy after a failed transvenous approach. The system
      was programmed in an LV tip-right ventricular coil configuration, but during
      follow-up loss of LV capture with recurrence of symptoms occurred. Changing to an
      LV tip-LV ring configuration restored LV pacing through anodal capture. Loss of
      cathodal capture was caused by dislodgment of the cathodal electrode due to a
      broken fixation suture. Anodal capture was used to reinstall resynchronization
      therapy, which resulted in clinical improvement. There were no adverse effects
      from anodal stimulation in a follow-up period of 6 months.

PMID- 16441725
TI  - Catheter ablation for an incessant form of antiarrhythmic drug-resistant
      ventricular fibrillation after acute coronary syndrome.
AB  - A 77-year-old man was admitted with an acute coronary syndrome (ACS), severe
      heart failure (HF), and repeated ventricular fibrillation (VF) episodes. A single
      premature ventricular complex (PVC) induced ventricular tachycardia (VT), which
      degenerated to VF reproducibly. This PVC was eliminated by catheter ablation at
      the left ventricular posteroseptal region where double Purkinje potentials
      preceding the ventricular wave had been recorded. The electrical storm
      disappeared, and programmable stimulation failed to induce any tachyarrhythmias
      after the ablation. A Purkinje fiber network-related PVC served as a trigger and
      as a substrate for VT and VF in a case of ACS with HF.

PMID- 16441726
TI  - A case of transient 2:1 atrioventricular block, resolved by thyroxine
      supplementation for subclinical hypothyroidism.
AB  - A 42-year-old man was admitted to our hospital with palpitation attacks. Holter
      ECG showed 2:1 atrioventricular block and bradycardia with the minimum heart rate
      of 44 beats/min. There was a possible indication of electrophysiological study
      and cardiac pacemaker implantation. Laboratory data on admission revealed
      elevated thyrotropin level, with normal thyroxine level. To rule out functional
      atrioventricular block, we tried 2 weeks of the thyroxine supplementation, and
      Holter ECG showed improved heart rate without any atrioventricular block or long
      pause. We experienced that subclinical hypothyroidism caused severe bradycardia
      and 2:1 atrioventricular block, and that thyroxine supplementation completely
      improved these conditions.

PMID- 16441727
TI  - Concordance between an electroanatomic mapping system and cardiac MRI in
      arrhythmogenic right ventricular cardiomyopathy.
AB  - A 29-year-old man presenting with syncopal ventricular tachycardia was diagnosed
      with arrhythmogenic right ventricular (RV) cardiomyopathy. Cardiac magnetic
      resonance imaging (MRI) revealed an unequivocal dyskinetic segment at the basal
      portion of the RV lateral free wall. Three-dimensional electroanatomic voltage
      mapping using the EnSite NavX system recorded a low voltage area corresponding to
      the diseased portion of the right ventricle identified by MRI. This report
      describes concordance between cardiac MRI and this novel mapping system in
      arrhythmogenic RV cardiomyopathy.

PMID- 16441728
TI  - Strategy for safe performance of magnetic resonance imaging on a patient with
      implantable cardioverter defibrillator.
AB  - Clinically indicated magnetic resonance imaging (MRI) of the brain was safely
      performed at 1.5 T on a patient with an implantable cardioverter defibrillator
      (ICD). The ICD was reprogrammed to detection only, and imaging hardware and
      protocols were modified to minimize radiofrequency power deposition to the ICD
      system. The integrity of the ICD system was verified immediately post-MRI and
      after 6 weeks, including an ICD test with induction of ventricular fibrillation.
      This case demonstrates that in exceptional circumstances, in carefully selected
      patients, and using special precautions, an MRI exam of the brain may be possible
      in patients with ICDs.

PMID- 16441729
TI  - Modulation of clinical expression of plaque-induced gingivitis: response in
      aggressive periodontitis subjects.
AB  - AIM: The aim of this study was to characterize the gingival inflammatory response
      to de novo plaque accumulation in subjects treated for aggressive periodontitis
      (AP). The gingival inflammatory response of the AP subjects was retrospectively
      compared with that of periodontally healthy individuals (PH) matched for exposure
      to plaque and of periodontally healthy subjects previously identified as "high
      responders" (HR) and "low responders" (LR). MATERIALS AND METHODS: 13 AP subjects
      and 26 matched PH subjects participated in a 21-day experimental gingivitis
      trial. Plaque index (PlI), Gingival index (GI), gingival crevicular fluid volume
      (GCF) and angulated bleeding score (AngBS) were recorded at days 0, 7, 14 and 21.
      Cumulative plaque exposure (CPE), i.e. PlI over time, was also calculated.
      RESULTS: GCF was significantly higher in AP compared with PH group at each
      observation interval (p< or =0.001). In addition, GCF was significantly higher in
      AP group compared with either LR or HR groups at each observation interval
      (p<0.001). CONCLUSIONS: These results suggest that susceptibility to gingival
      inflammation in response to de novo plaque accumulation may be related to
      susceptibility to periodontitis.

PMID- 16441730
TI  - Anti-gingivitis effect of a dentifrice containing bioactive glass (NovaMin)
      particulate.
AB  - BACKGROUND: The objective of this pilot clinical trial was to evaluate the anti
      gingivitis and anti-plaque effects of a dentifrice containing bioactive glass
      (NovaMin) compared with a placebo control dentifrice in a 6 weeks clinical study.
      METHODS: The study design was a randomized, double-blinded, controlled clinical
      trial. One hundred volunteers took part in the study and were matched for plaque
      index (PLI), gingival bleeding index (GBI), age and gender. The protocol was
      reviewed and approved by the Ethical Committee of the University. The subjects
      received a supragingival prophylaxis to remove all plaque, calculus and extrinsic
      stain. Following the baseline examination, subjects were instructed to brush with
      their assigned dentifrice and toothbrush. The PLI and GBI were determined for the
      baseline and 6 weeks. The data were analysed using a repeated-measures anova
      conducted on the two dependent measures to compare the effect between the test
      and control group. RESULTS: Ninety-five subjects finished the study. The results
      showed that the PLI (baseline=1.54, 6 weeks=1.29) and GBI (baseline=1.14, 6
      weeks=0.47) were significantly reduced, respectively, over the 6 weeks period in
      the test group (p<0.001 for each measure). There was a 58.8% reduction in
      gingival bleeding and a 16.4% reduction in plaque growth. There was no difference
      of the PLI (baseline=1.60, 6 weeks=1.57) and GBI (baseline=1.18, 6-week=1.02)
      over the 6 week period in the control group. CONCLUSION: This study demonstrated
      that a dentifrice containing NovaMin significantly improves oral health as
      measured by a reduction in gingival bleeding and reduction in supragingival
      plaque compared with a negative dentifrice over the 6 weeks study period.

PMID- 16441732
TI  - The importance of assessing confounding and effect modification in research
      involving periodontal disease and systemic diseases.

PMID- 16441731
TI  - Gingivitis, dental caries and tooth loss: risk factors for cardiovascular
      diseases or indicators of elevated health risks.
AB  - OBJECTIVES: The results of earlier studies connecting dental diseases to
      cardiovascular diseases are inconsistent. Our aim in this cross-sectional study
      was to investigate whether there are associations of dental diseases and
      diagnosed angina pectoris among the 1966 Northern Finland Birth Cohort. MATERIALS
      AND METHODS: A postal questionnaire was sent to all cohort members in 1997-1998.
      The number of replies totalled 8690. Angina pectoris was determined by asking
      whether the respondent had been diagnosed with angina pectoris. Gingivitis,
      dental caries and tooth loss were determined on the basis of self-reported
      gingival bleeding, presence of dental caries and six or more missing teeth.
      RESULTS: We found overall associations of gingivitis (odds ratio (OR) 1.52,
      confidence interval (CI) 1.04-2.22), dental caries (OR 1.50, CI 1.04-2.18) and
      tooth loss (OR 1.53, CI 0.69-3.42) with the presence of angina pectoris. The
      associations were modified by gender and socioeconomic status. In addition,
      gingivitis, dental caries and tooth loss were also associated with several
      cardiovascular risk factors. CONCLUSION: There were associations of self-reported
      gingivitis, dental caries and tooth loss with angina pectoris. However, the
      associations between dental diseases and cardiovascular risk factors suggest that
      the associations may be because of confounding.

PMID- 16441733
TI  - Confounding and effect modification: possible explanation for variation in the
      results on the association between oral and systemic diseases.
AB  - OBJECTIVES: There is large variation in the results of studies on the association
      between periodontitis and systemic diseases. The variation might be explained by
      the fact that the association between periodontitis and systemic diseases is
      confounded, or the association might be modified by extraneous factors. In this
      article, we show, using simple examples, how confounding and effect modification
      may cause variation in results. In addition, these examples show that
      uncontrolled or partially controlled confounders can induce spurious
      associations. CONCLUSION: Confounding and effect modification may explain the
      variation in the results of studies on the association between periodontitis and
      systemic diseases.

PMID- 16441734
TI  - Association between psychosocial factors and periodontitis: a case-control study.
AB  - OBJECTIVE: This case-control study investigated the association between life
      events, anxiety, and depression with periodontitis. METHODOLOGY: The study
      counted with 165 individuals, both sexes, 35-60 years of age. Case group included
      96 individuals suffering from periodontal disease; and in control group 69
      subjects with no history of periodontitis. Clinical examinations were performed
      by a single examiner. Psychological assessment included four inventories: Life
      Events Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory and Beck
      Depression Inventory. Bivariate and multivariate logistic regression analyses
      were performed to compare cases and controls. RESULTS: Mean probing depth and
      clinical attachment level were 3.44+/-0.80 and 4.01+/-1.61 in the case group and
      1.96+/-0.19 and 0.95+/-0.50 in the control group, respectively (p<0.05). Positive
      association of periodontitis with age (odds ratio (OR)=1.15 95% confidence
      interval (CI): 1.06-1.24), male gender (OR=2.71, CI: 1.13-6.49), smoking
      (OR=6.05, CI: 1.67-21.94) and educational level (OR=6.49, CI: 1.14-36.95) was
      confirmed. Bivariate analysis did not demonstrate significant mean differences in
      life events, anxiety symptoms, trait or state of anxiety, or depression symptoms
      between cases and controls. Multivariate logistic regression, controlling for
      confounding factors, demonstrated no significant association between psychosocial
      factors and periodontal disease. CONCLUSIONS: Within the limits of this study it
      is possible to conclude that there was no significant association between
      periodontitis and the psychosocial factors analysed.

PMID- 16441735
TI  - The relationship between maternal periodontitis, adverse pregnancy outcome and
      miscarriage in never smokers.
AB  - BACKGROUND: It has been postulated that associations between periodontal disease
      and systemic conditions may be because of the confounding effects of smoking. In
      addition, studies of this type rarely investigate the adverse pregnancy outcome
      of miscarriage. AIM: The aim of this prospective study was to investigate a
      relationship between periodontal disease in pregnancy and subsequent adverse
      pregnancy outcomes in a population of never smokers. MATERIALS AND METHODS:
      Pregnant women were recruited at 12 weeks gestation. Demographic, behavioural and
      medical data were collected. A periodontal examination was performed and data on
      each subjects' pregnancy outcome were collected. RESULTS: A total of 1793 women
      reported never previously smoking. Of these, 7.3% had a pre-term birth and 0.9% a
      late miscarriage. As expected in this population, we found no associations
      between poorer periodontal health and either pre-term birth or low birth weight
      (LBW). In contrast, the subjects who experienced a late miscarriage had a higher
      mean probing depth at mesial sites compared with the subjects that gave birth at
      term (2.69 mm versus 2.41 mm, p=0.006). CONCLUSIONS: There was an association
      between some measures of periodontal disease and late miscarriage; however, there
      was no association between periodontitis and pre-term birth or LBW in this
      population.

PMID- 16441736
TI  - Periodontal status among relatives of aggressive periodontitis patients and
      reliability of family history report.
AB  - OBJECTIVES: To assess the periodontal status of relatives of Aggressive
      Periodontitis (AgP) patients, and to evaluate the reliability of the family
      history report as provided by the proband. MATERIAL AND METHODS: Data from 54 AgP
      patients were gathered along with a family history report for each of their
      relatives. Only 27 patients (probands) had relatives willing to be examined. This
      yielded a total of 61 relatives from whom the periodontal status was obtained.
      The family history report for each examined relative was compared with the
      periodontal diagnosis made at examination to assess reliability. RESULTS: Eight
      percentage of the examined relatives, aged between 12-76, were diagnosed with
      AgP, while chronic periodontitis was present in 39%, gingivitis in 38% and 15%
      were healthy. If the report provided by the proband was positive, the likelihood
      of finding any type of periodontitis in that relative was 85.7%, whereas if the
      report was negative the likelihood of the absence of periodontitis was 70.6%.
      CONCLUSION: The percentage of examined relatives who were affected with AgP (8%),
      although lower than percentages reported in other AgP family studies, was still
      higher than the prevalence of the condition in random populations. Reliability of
      periodontal family history was considered good and more reliable when it was
      positive.

PMID- 16441737
TI  - Hyper-reactive mononuclear cells and neutrophils in chronic periodontitis.
AB  - OBJECTIVES: Stimulated mono- and polymorphonuclear cells from patients with
      periodontitis have shown increased release of interleukin-1beta (IL-1beta) and
      oxygen radicals, respectively. The aim was to study whether this hyper-reactivity
      could be found both in mono- and polymorphonuclear cells from the same patient,
      and whether there was a relation to the gene coding for IL-1beta (IL
      1beta(+3953)). MATERIAL AND METHODS: Peripheral mononuclear cells from 14 non
      smoking and well-treated patients and pair-matched controls were incubated with
      opsonized Staphylococcus aureus and lipopolysaccharide (LPS). Released IL-1beta
      and tumour necrosis factor (TNF)-alpha were determined with ELISA. Generation of
      oxygen radicals from the Fcgamma-receptor-stimulated neutrophils was measured
      with chemiluminescence and the polymorphism at IL-1beta(+3953) was measured with
      polymerase chainreaction. RESULTS: The mononuclear cells from the patients
      released more IL-1beta after incubation with LPS (p<0.001) and with bacteria
      (p<0.05). The release of TNF-alpha tended to be higher in the patient group. The
      peripheral neutrophils from the patients generated more oxygen radicals (p<0.06).
      We found no differences between the study groups regarding the IL-1beta(+3953)
      polymorphism. CONCLUSION: The similarity in systemic inflammation between
      patients and controls suggests that the increased release/generation of IL-1beta
      and oxygen radicals from peripheral leukocytes in periodontitis patients is of a
      constitutional nature and of pathogenic relevance.

PMID- 16441738
TI  - In vitro calculus detection with a moved smart ultrasonic device.
AB  - STUDY OBJECTIVE: The objective of subgingival instrumentation of periodontally
      diseased root surfaces is to remove the adhering microbial biofilm and calcified
      deposits. Recently, we have described an automated calculus detection system
      under static conditions. Clinically however, the tip of the system has to be
      moved over tooth surfaces. It was thus necessary to study the entire system in
      motion. METHODS: The detection device is based on a conventional dental
      piezoelectric ultrasonic handpiece with a conventional scaler insert. The impulse
      response of the mechanical oscillation system is analysed by a fuzzy logic-based
      computerized algorithm, which classifies various surfaces. The present study
      investigates dental surface recognition properties of the new system with the tip
      being moved over teeth surfaces in vitro. Following a training set of 7977
      measurements (3960 calculus, 4017 cement) on 200 extracted teeth, 1363
      measurements were conducted on 34 teeth unknown to the system. RESULTS: The
      surfaces cementum and calculus were correctly classified in 78% within the
      training set and in 81% within the set unknown, with a kappa value of 0.68.
      CONCLUSION: It was shown that this method of automatic recognition of tooth
      surfaces is able to distinguish between different tooth surfaces in vitro
      independently from tip movements.

PMID- 16441740
TI  - Supportive periodontal therapy using mechanical instrumentation or 2% minocycline
      gel: a 12 month randomized, controlled, single masked pilot study.
AB  - OBJECTIVE: To compare the short-term performance of subgingival local delivery of
      2% minocycline gel and conventional subgingival debridement in supportive
      periodontal therapy (SPT) patients. METHODS: Forty adult patients having
      completed active treatment for moderate to advanced chronic periodontitis were
      included in a randomized, controlled, single masked maintenance care pilot study.
      Sites with residual pocket probing depths > or =5 mm and bleeding on probing were
      treated with either minocycline gel (minocycline-group) or scaling and root
      planing only (debridement-group) at baseline, 3, 6, and 9 months. Clinical and
      microbiological examinations were performed at baseline, 3, 6, 9, and 12 months.
      RESULTS: Full-mouth plaque and bleeding scores remained <10% and <20%,
      respectively, for both groups throughout the study. In both groups there was a
      persistent reduction in number of teeth and sites with probing pocket depths > or
      =5 mm (p<0.05) with no significant differences between the groups. The prevalence
      of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola,
      Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Prevotella
      nigrescens, remained at levels < or =10(5) in the majority of patients and sites
      in both groups. CONCLUSION: This pilot study failed to show a difference between
      local delivery of 2% minocycline gel as mono-therapy and traditional subgingival
      debridement in patients on SPT.

PMID- 16441739
TI  - Effect of rhPDGF-BB on bone turnover during periodontal repair.
AB  - PURPOSE: Growth factors such as platelet-derived growth factor (PDGF) exert
      potent effects on wound healing including the regeneration of periodontia.
      Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP)
      is a well-known biomarker of bone turnover, and as such is a potential indicator
      of osseous metabolic activity. The objective of this study was to evaluate the
      release of the ICTP into the periodontal wound fluid (WF) following periodontal
      reconstructive surgery using local delivery of highly purified recombinant human
      PDGF (rhPDGF)-BB. METHODS: Forty-seven human subjects at five treatment centres
      possessing chronic severe periodontal disease were monitored longitudinally for
      24 weeks following PDGF regenerative surgical treatment. Severe periodontal
      osseous defects were divided into one of three groups and treated at the time of
      surgery with either: beta-tricalcium phosphate (TCP) osteoconductive scaffold
      alone (active control), beta-TCP+0.3 mg/ml of rhPDGF-BB, or beta-TCP+1.0 mg/ml of
      rhPDGF-BB. WF was harvested and analysed for local ICTP levels by
      radioimmunoassay. Statistical analysis was performed using analysis of variance
      and an area under the curve analysis (AUC). RESULTS: The 0.3 and 1.0 mg/ml PDGF
      BB treatment groups demonstrated increases in the amount of ICTP released locally
      for up to 6 weeks. There were statistically significant differences at the week 6
      time point between beta-TCP carrier alone group versus 0.3 mg/ml PDGF-BB group
      (p<0.05) and between beta-TCP alone versus the 1.0 mg/ml PDGF-BB-treated lesions
      (p<0.03). The AUC analysis revealed no statistical differences amongst groups.
      CONCLUSION: This study corroborates the release of ICTP as a measure of active
      bone turnover following local delivery of PDGF-BB to periodontal osseous defects.
      The amount of ICTP released from the WF revealed an early increase for all
      treatment groups. Data from this study suggests that when PDGF-BB is delivered to
      promote periodontal tissue engineering of tooth-supporting osseous defects, there
      is a direct effect on ICTP released from the wound.

PMID- 16441741
TI  - Evaluating the quality of active-control trials in periodontal research.
AB  - AIM: The increasing popularity of randomized-controlled trials (RCTs) has raised
      the issue of their quality. Frequently overlooked are the differences between
      superiority and equivalence trials. The purpose of this study was to apply
      specific methodological criteria to evaluate the quality of active-control trials
      using studies that compared guided tissue regeneration (GTR) with enamel matrix
      derivatives (EMD). MATERIALS AND METHODS: Seven RCTs were identified in the
      literature. Standard methodological criteria and seven additional criteria for
      trials using active-control groups were used to evaluate the quality of the seven
      RCTs. RESULTS: Two trials were considered as superiority trials. The remaining
      five provided no clear statement of their research aim. However, two claimed that
      EMD and GTR were equally effective, because their results failed to show a
      significant difference between EMD and GTR. Most trials did not meet the majority
      of the design criteria. CONCLUSIONS: The general lack of compliance with quality
      criteria might place doubt on the value of these trials and may render any
      conclusions questionable. It is therefore important to distinguish clearly
      between superiority trials and equivalence trials, and to incorporate appropriate
      additional criteria in the design of future RCTs with active-control groups.

PMID- 16441743
TI  - Antimicrobial resistance in the subgingival microflora in patients with adult
      periodontitis. A comparison between The Netherlands and Spain.

PMID- 16441744
TI  - Pollination mutualisms in Caryophyllaceae.

PMID- 16441745
TI  - Visualising patterns of CO2 diffusion in leaves.

PMID- 16441746
TI  - When enemies attack do plants get by with a little help from their friends?

PMID- 16441747
TI  - Plasma membrane anion channels in higher plants and their putative functions in
      roots.
AB  - Recent years have seen considerable progress in identifying anion channel
      activities in higher plant cells. This review outlines the functional properties
      of plasma membrane anion channels in plant cells and discusses their likely roles
      in root function. Plant anion channels can be grouped according to their voltage
      dependence and kinetics: (1) depolarization-activated anion channels which
      mediate either anion efflux (R and S types) or anion influx (outwardly rectifying
      type); (2) hyperpolarization-activated anion channels which mediate anion efflux,
      and (3) anion channels activated by light or membrane stretch. These types of
      anion channel are apparent in root cells where they may function in anion
      homeostasis, membrane stabilization, osmoregulation, boron tolerance and
      regulation of passive salt loading into the xylem vessels. In addition, roots
      possess anion channels exhibiting unique properties which are consistent with
      them having specialized functions in root physiology. Most notable are the
      organic anion selective channels, which are regulated by extracellular Al3+ or
      the phosphate status of the plant. Finally, although the molecular identities of
      plant anion channels remain elusive, the diverse electrophysiological properties
      of plant anion channels suggest that large and diverse multigene families
      probably encode these channels.

PMID- 16441748
TI  - Pollination and seed predation by moths on Silene and allied Caryophyllaceae:
      evaluating a model system to study the evolution of mutualisms.
AB  - Nursery pollinators, and the plants they use as hosts for offspring development,
      function as exemplary models of coevolutionary mutualism. The two pre-eminent
      examples--fig wasps and yucca moths--show little variation in the interaction:
      the primary pollinator is an obligate mutualist. By contrast, nursery pollination
      of certain Caryophyllaceae, including Silene spp., by two nocturnal moth genera,
      Hadena and Perizoma, ranges from antagonistic to potentially mutualistic,
      offering an opportunity to test hypotheses about the factors that promote or
      discourage the evolution of mutualism. Here, we review nursery pollination and
      host-plant interactions in over 30 caryophyllaceous plants, based on published
      studies and a survey of researchers investigating pollination, seed predation,
      and moth morphology and behavior. We detected little direct evidence of mutualism
      in these moth-plant interactions, but found traits and patterns in both that are
      nonetheless consistent with the evolution of mutualism and merit further
      attention.

PMID- 16441749
TI  - Expressed sequence-tag analysis in Casuarina glauca actinorhizal nodule and root.
AB  - The present study aimed to identify and assess the frequency and tissue
      specificity of plant genes in the actinorhizal Casuarina glauca-Frankia symbiosis
      through expressed sequence tag (EST) analysis. Using a custom analysis pipeline
      for raw sequences of C. glauca uninfected roots and nodules, we obtained an EST
      databank web interface. Gene expression was studied in nodules vs roots using
      comparative quantitative real-time reverse transcription-polymerase chain
      reaction (qRT-PCR). From roots and nodules, 2028 ESTs were created and clustered
      in 242 contigs and 1429 singletons, giving a total of 1616 unique genes. Half the
      nodule transcripts showed no similarity to previously identified genes. Genes of
      primary metabolism, protein synthesis, cell division and defence were highly
      represented in the nodule library. Differential expression was observed between
      roots and nodules for several genes linked to primary metabolism and flavonoid
      biosynthesis. This comparative EST-based study provides the first picture of the
      set of genes expressed during actinorhizal symbiosis. We consider our database to
      be a flexible tool that can be used for the management of EST data from other
      actinorhizal symbioses.

PMID- 16441750
TI  - Relative effects of nocturnal vs diurnal pollinators and distance on gene flow in
      small Silene alba populations.
AB  - Silene alba exists in natural metapopulations throughout its range and is visited
      by a suite of both diurnal and nocturnal pollinators. Pollen-mediated gene flow
      may help reduce genetic isolation of subpopulations. Here, we compared the
      relative effects of nocturnal vs diurnal pollinators on pollen-mediated gene flow
      in subpopulations separated by two distance treatments. We established
      populations consisting of genetically marked individuals in an old field in
      Tennessee (USA). Electrophoretic examination of seedlings produced by plants
      exposed to nocturnal, diurnal and control pollinator treatments and separated by
      either 20 or 80 m allowed us to directly measure pollen-mediated gene flow. Gene
      flow was more common between populations separated by only 20 m. Nocturnal
      pollinators were responsible for most gene flow between populations, regardless
      of distance. Diurnal pollinators played only a small role in pollen-mediated gene
      flow. The results suggest that nocturnal pollinators are better than diurnal
      pollinators at moving pollen between small S. alba subpopulations. However, their
      effectiveness declines as the distance between subpopulations increases, making
      them relatively ineffective at moving genes between isolated subpopulations.

PMID- 16441751
TI  - Pollination crisis in the butterfly-pollinated wild carnation Dianthus
      carthusianorum?
AB  - Knowledge of pollination services provided by flower visitors is a prerequisite
      for understanding (co)evolutionary processes between plants and their
      pollinators, for evaluating the degree of specialization in the pollination
      system, and for assessing threats from a potential pollination crisis. This study
      examined pollination efficiency and visitation frequency of pollinators--key
      traits of pollinator-mediated fecundity--in a natural population of the wild
      carnation Dianthus carthusianorum. The five lepidopteran pollinator species
      observed differed in pollination efficiency and visitation frequency. Pollinator
      importance, the product of pollination efficiency and visitation frequency, was
      determined by the pollinator's visitation frequency. Pollination of D.
      carthusianorum depended essentially on only two of the five recorded pollinator
      species. Seed set was pollen-limited and followed a saturating dose-response
      function with a threshold of c. 50 deposited pollen grains for fruit development.
      Our results confirm that D. carthusianorum is specialized to lepidopteran
      pollinators, but is not particularly adapted to the two main pollinator species
      identified. The local persistence of D. carthusianorum is likely to be at risk as
      its reproduction depends essentially on only two of the locally abundant, but
      generally vulnerable, butterfly species.

PMID- 16441752
TI  - Nursery pollination by a moth in Silene latifolia: the role of odours in
      eliciting antennal and behavioural responses.
AB  - Since the 1970s it has been known that the nursery pollinator Hadena bicruris is
      attracted to the flowers of its most important host plant, Silene latifolia, by
      their scent. Here we identified important compounds for attraction of this
      noctuid moth. Gas chromatographic and electroantennographic methods were used to
      detect compounds eliciting signals in the antennae of the moth.
      Electrophysiologically active compounds were tested in wind-tunnel bioassays to
      foraging naive moths, and the attractivity of these compounds was compared with
      that to the natural scent of whole S. latifolia flowers. The antennae of moths
      detected substances of several classes. Phenylacetaldehyde elicited the strongest
      signals in the antennae, but lilac aldehydes were the most attractive compounds
      in wind-tunnel bioassays and attracted 90% of the moths tested, as did the scent
      of single flowers. Our results show that the most common and abundant floral
      scent compounds in S. latifolia, lilac aldehydes, attracted most of the moths
      tested, indicating a specific adaptation of H. bicruris to its host plant.

PMID- 16441753
TI  - Coping with third parties in a nursery pollination mutualism: Hadena bicruris
      avoids oviposition on pathogen-infected, less rewarding Silene latifolia.
AB  - In nursery pollination systems, pollinator offspring usually feed on pollinated
      fruits or seeds. Costs and benefits of the interaction for plant and pollinator,
      and hence its local outcome (antagonism-mutualism), can be affected by the
      presence of 'third-party' species. Infection of Silene latifolia plants by the
      fungus Microbotryum violaceum halts the development of fruits that provide
      shelter and food for larvae of the pollinating moth Hadena bicruris. We
      investigated whether the moth secures its benefit by selective oviposition on
      uninfected flowers. Oviposition was recorded in eight natural populations as a
      function of plant infection status, local neighbourhood, plant and flower
      characteristics. Oviposition was six times lower on flowers from infected than on
      those from uninfected plants. Oviposition decreased with decreasing flower and
      ovary size. Moths could use the latter to discriminate against diseased flowers.
      Although moths show an adaptive oviposition response, they reduce the future
      potential of healthy hosts because they still visit infected plants for nectar,
      vectoring the disease, and they reduce any fitness advantage gained by disease
      resistant plants through selective predation of those plants.

PMID- 16441754
TI  - Natural selection on floral traits of female Silene dioica by a sexually
      transmitted disease.
AB  - Floral traits endowing high reproductive fitness can also affect the probability
      of plants contracting sexually transmitted diseases. We explore how variations in
      floral traits influence the fitness of Silene dioica females in their
      interactions with pollinators carrying pollen or spores of the sterilizing anther
      smut fungus Microbotryum violaceum. We collected healthy and infected plants in a
      highly diseased population and grew them under conditions that 'cure' infected
      individuals, and used standard regression methods to detect natural selection on
      floral traits. Narrow-sense heritabilities, coefficients of additive genetic
      variation (CV(A)) and genetic correlations among traits were estimated from
      paternal half-sib groups. Pollinator preferences imposed strong direct and
      directional selection on traits affecting female attractiveness and pollen-/spore
      capturing abilities. Levels of additive genetic variance were high in these
      traits, suggesting that rapid responses to selection are possible. By considering
      our results in the light of spatial and temporal heterogeneity resulting from the
      colonization dynamics typical for this species, we suggest that the conflicting
      selective effects of pollen/spore loads lead to the maintenance of genetic
      variation in these traits.

PMID- 16441755
TI  - Seed fitness of hermaphrodites in areas with females and anther smut disease:
      Silene acaulis and Microbotryum violaceum.
AB  - Sex-dependent infection rates could change the effective sex ratio of a
      population. Here, I tested whether females and hermaphrodites of Silene acaulis
      were equally likely to be infected by Microbotryum violaceum, a fungus that
      sterilizes the host, and whether sex allocation in hermaphrodites differed
      between low and high disease plots. Sex ratios of healthy and diseased plants
      were estimated in five natural plots. Fitness gained through seed production was
      estimated by measuring seed quantity and quality for each sex morph in eight
      plots for 2 yr; four plots had 1-5% disease frequency and four plots had 18-25%
      disease frequency. Sex ratios of healthy and diseased plants did not differ in
      five plots. The proportion of fitness hermaphrodites gained through ovules varied
      from 25 to 48%, indicating that this population is near the cosexual end of
      gynodioecy. Variation in functional gender of hermaphrodites was not explained by
      sex-dependent infection rates. Spatial heterogeneity in resources and
      microclimate seems to be important in explaining both disease frequency and
      variation in seed production by females and hermaphrodites.

PMID- 16441756
TI  - Physical map of the wheat high-grain protein content gene Gpc-B1 and development
      of a high-throughput molecular marker.
AB  - Grain protein content (GPC) is important for human nutrition and has a strong
      influence on pasta and bread quality. A quantitative trait locus, derived from a
      Triticum turgidum ssp. dicoccoides accession (DIC), with an average increase in
      GPC of 14 g kg(-1) was mapped on chromosome 6BS. Using the wheat-rice
      colinearity, a high-density map of the wheat region was developed and the
      quantitative trait locus was mapped as a simple Mendelian locus designated Gpc
      B1. A physical map of approx. 250 kb of the Gpc-B1 region was developed using a
      tetraploid wheat bacterial artificial chromosome library. The constructed
      physical map included the two Gpc-B1 flanking markers and one potential candidate
      gene from the colinear rice region completely linked to Gpc-B1. The relationship
      between physical and genetic distances and the feasibility of isolating genes by
      positional cloning in wheat are discussed. A high-throughput codominant marker,
      Xuhw89, was developed. A 4-bp deletion present in the DIC allele was absent in a
      collection of 117 cultivated tetraploid and hexaploid wheat germplasm, suggesting
      that this marker will be useful to incorporate the high GPC allele from the DIC
      accession studied here into commercial wheat varieties.

PMID- 16441757
TI  - Impact of drought on productivity and water use efficiency in 29 genotypes of
      Populus deltoides x Populus nigra.
AB  - We examined the relationships among productivity, water use efficiency (WUE) and
      drought tolerance in 29 genotypes of Populus x euramericana (Populus deltoides x
      Populus nigra), and investigated whether some leaf traits could be used as
      predictors for productivity, WUE and drought tolerance. At Orleans, France,
      drought was induced on one field plot by withholding water, while a second plot
      remained irrigated and was used as a control. Recorded variables included stem
      traits (e.g. biomass) and leaf structural (e.g. leaf area) and functional traits
      [e.g. intrinsic water use efficiency (Wi) and carbon isotope discrimination
      (Delta)]. Productivity and Delta displayed large genotypic variability and were
      not correlated. Delta scaled negatively with Wi and positively with stomatal
      conductance under moderate drought, suggesting that the diversity for Delta was
      mainly driven by stomatal conductance. Most of the productive genotypes displayed
      a low level of drought tolerance (i.e. a large reduction of biomass), while the
      less productive genotypes presented a large range of drought tolerance. The
      ability to increase WUE in response to water deficit was necessary but not
      sufficient to explain the genotypic diversity of drought tolerance.

PMID- 16441759
TI  - Two patterns of leaf photosynthetic response to irradiance transition from
      saturating to limiting one in some plant species.
AB  - Plants often regulate the amount and size of light-harvesting antenna (LHCII) to
      maximize photosynthesis at low light and avoid photodamage at high light. Gas
      exchange, 77 K chlorophyll fluorescence, photosystem II (PSII) electron transport
      as well as LHCII protein were measured in leaves irradiated at different light
      intensities. After irradiance transition from saturating to limiting one leaf
      photosynthetic rate in some species such as soybean and rice declined first to a
      low level, then increased slowly to a stable value (V pattern), while in other
      species such as wheat and pumpkin it dropped immediately to a stable value (L
      pattern). Saturating pre-irradiation led to significant declines of both 77 K
      fluorescence parameter F685/F735 and light-limited PSII electron transport rate
      in soybean but not in wheat leaves, indicating that some LHCIIs dissociate from
      PSII in soybean but not in wheat leaves. The L pattern of LHCII-decreased rice
      mutant and the V pattern of its wild type demonstrate that the V pattern is
      linked to dissociation/reassociation of some LHCIIs from/to PSII.

PMID- 16441758
TI  - Lateral diffusion of CO2 from shaded to illuminated leaf parts affects
      photosynthesis inside homobaric leaves.
AB  - Gas exchange is generally regarded to occur between the leaf interior and ambient
      air, i.e. in vertical (anticlinal) directions of leaf blades. However, inside
      homobaric leaves, gas movement occurs also in lateral directions. The aim of the
      present study was to ascertain whether lateral CO2 diffusion affects leaf
      photosynthesis when illuminated leaves are partially shaded. Measurements using
      gas exchange and chlorophyll fluorescence imaging techniques were performed on
      homobaric leaves of Vicia faba and Nicotiana tabacum or on heterobaric leaves of
      Glycine max and Phaseolus vulgaris. For homobaric leaves, gas exchange inside a
      clamp-on leaf chamber was affected by shading the leaf outside the chamber. The
      quantum yield of photosystem II (Phi(PSII)) was highest directly adjacent to a
      light/shade border (LSB). Phi(PSII) decreased in the illuminated leaf parts with
      distance from the LSB, while the opposite was observed for nonphotochemical
      quenching. These effects became most pronounced at low stomatal conductance. They
      were not observed in heterobaric leaves. The results suggest that plants with
      homobaric leaves can benefit from lateral CO2 flux, in particular when stomata
      are closed (e.g. under drought stress). This may enhance photosynthetic, instead
      of nonphotochemical, processes near LSBs in such leaves and reduce the
      photoinhibitory effects of excess light.

PMID- 16441760
TI  - Enhanced monsoon precipitation and nitrogen deposition affect leaf traits and
      photosynthesis differently in spring and summer in the desert shrub Larrea
      tridentata.
AB  - Leaf-level CO2 assimilation (A(area)) can largely be predicted from stomatal
      conductance (g(s)), leaf morphology (SLA) and nitrogen (N) content (N(area)) in
      species across biomes and functional groups. The effects of simulated global
      change scenarios, increased summer monsoon rain (+H2O), N deposition (+N) and the
      combination (+H2O +N), were hypothesized to affect leaf trait-photosynthesis
      relationships differently in the short- and long-term for the desert shrub Larrea
      tridentata. During the spring, +H2O and +H2O +N plants had lower A(area) and
      g(s), but similar shoot water potential (Psi(shoot)) compared with control and +N
      plants; differences in A(area) were attributed to lower leaf N(area) and g(s).
      During the summer, +H2O and +H2O +N plants displayed higher A(area) than control
      and +N plants, which was attributed to higher Psi(shoot), g(s) and SLA.
      Throughout the year, A(area) was strongly correlated with g(s) but weakly
      correlated with leaf N(area) and SLA. We concluded that increased summer monsoon
      had a stronger effect on the performance of Larrea than increased N deposition.
      In the short term, the +H2O and +H2O +N treatments were associated with
      increasing A(area) in summer, but also with low leaf N(area) and lower A(area) in
      the long term the following spring.

PMID- 16441761
TI  - Two mire species respond differently to enhanced ultraviolet-B radiation: effects
      on biomass allocation and root exudation.
AB  - Increased ultraviolet-B (UV-B) radiation arising from stratospheric ozone
      depletion may influence soil microbial communities via effects on plant carbon
      allocation and root exudation. Eriophorum angustifolium and Narthecium ossifragum
      plants, grown in peatland mesocosms consisting of Sphagnum peat, peat pore water
      and natural microbial communities, were exposed outdoors to enhanced UV-B
      radiation simulating 15% ozone depletion in southern Scandinavia for 8 wk.
      Enhanced UV-B increased rhizome biomass and tended to decrease the biomass of the
      largest root fraction of N. ossifragum and furthermore decreased dissolved
      organic carbon (DOC) and monocarboxylic acid concentration, which serves as an
      estimate of net root exudation, in the pore water of the N. ossifragum mesocosms.
      Monocarboxylic acid concentration was negatively related to the total carbon
      concentration of N. ossifragum leaves, which was increased by enhanced UV-B. By
      contrast, enhanced UV-B tended to increase monocarboxylic acid concentration in
      the rhizosphere of E. angustifolium and its root : shoot ratio. Microbial biomass
      carbon was increased by enhanced UV-B in the surface water of the E.
      angustifolium mesocosms. Increased UV-B radiation appears to alter below-ground
      biomass of the mire plants in species-specific patterns, which in turn leads to a
      change in the net efflux of root exudates.

PMID- 16441762
TI  - Ni2+ induces changes in the morphology of vacuoles, mitochondria and microtubules
      in Paxillus involutus cells.
AB  - Organelles of ectomycorrhizal fungi are known to respond to changes in the
      extracellular environment. The response of vacuoles, mitochondria and
      microtubules to short-term nickel (Ni2+) exposure were investigated in hyphal tip
      cells of a Paxillus involutus from a heavy metal-rich soil. Vacuoles,
      mitochondria and microtubules were labelled with Oregon Green 488 carboxylic acid
      diacetate, 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)) and anti-alpha-tubulin
      antibodies, respectively; hyphae were treated with NiSO4 in the range of 0-1 mmol
      l(-1) and examined microscopically. Untreated hyphal tip cells contained tubular
      vacuole and mitochondrial networks. Ni2+ caused loss of organelle tubularity and
      severe microtubule disruption that were exposure-time and concentration
      dependent. Fine tubular vacuoles thickened and eventually became spherical in
      some hyphae, tubular mitochondria fragmented and microtubules shortened and
      aggregated into patches in most hyphae. Tubular vacuoles reformed on NiSO4
      removal and tubular mitochondria in the presence of NiSO4 suggesting cellular
      detoxification. These results demonstrate that Ni2+ induces changes in organelle
      and microtubule morphology. Recovery of tubular organelles to pretreatment
      morphology after Ni2+ exposure suggests cellular detoxification of the metal ion.

PMID- 16441763
TI  - Mechanism of control of root-feeding nematodes by mycorrhizal fungi in the dune
      grass Ammophila arenaria.
AB  - Root-feeding herbivores can affect plant performance and the composition of
      natural plant communities, but there is little information about the mechanisms
      that control root herbivores in natural systems. This study explores the
      interactions between the pioneer dune grass Ammophila arenaria, arbuscular
      mycorrhizal fungi (AMF) and the root-feeding nematode Pratylenchus penetrans. Our
      objectives were to determine whether AMF can suppress nematode infection and
      reproduction and to explore the mechanisms of nematode control by AMF. A
      sequential inoculation experiment and a split-root experiment were designed to
      analyse the importance of plant tolerance and resistance and of direct
      competition between AMF and P. penetrans for the root herbivore and the plant.
      Root infection and multiplication of P. penetrans were significantly reduced by
      the native inoculum of AMF. Plant preinoculation with AMF further decreased
      nematode colonization and reproduction. Nematode suppression by AMF did not occur
      through a systemic plant response but through local mechanisms. Our results
      suggest that AMF are crucial for the control of root-feeding nematodes in natural
      systems and illustrate that locally operating mechanisms are involved in this
      process.

PMID- 16441765
TI  - Safety of donor right hepatectomy for adult-to-adult living donor liver
      transplantation.
AB  - The purpose of this study was to ascertain the usefulness of preoperative
      evaluations of donors by computed tomography (CT) volumetry and CT
      cholangiography for prevention of unexpected liver failure and biliary
      complications after donor right hepatectomy for adult-to-adult living donor liver
      transplantation. Fifty-two donors who underwent right hepatectomy without the
      middle hepatic vein were enrolled in this study. The values of graft weight (GW)
      were significantly correlated with those of estimated graft volume (GV; P <
      0.0001). GW was predicted by the following formula: GW = 155.25 + 0.658 x GV;
      r(2) = 0.489. CT cholangiography revealed anatomical variants of biliary
      structure in one-third of the donors and also clearly showed one or two small
      biliary branches from the caudate lobe to the right hepatic ducts or the
      confluence in 58% of the donors. Biliary leakage, which was treated by
      conservative therapy, occurred in only one donor (1.9%). No donors received
      homologous blood transfusion. Hyperbilirubinemia (serum total bilirubin >5 mg/dl)
      occurred in 5.8% of the donors during their early postoperative periods. Precise
      evaluations of liver remnant volume by CT volumetry and biliary variation by CT
      cholangiography are essential for performing safe donor hepatectomy, preventing
      hepatic insufficiency and minimizing the risk of biliary tract complications.

PMID- 16441766
TI  - Cardiac allograft vasculopathy in pediatric heart transplant recipients.
AB  - Metabolic parameters for coronary allograft vasculopathy (CAV) have not been well
      defined in children. CAV (by angiography or autopsy) was studied in 337 heart
      recipients on a cyclosporine-based steroid-sparing regimen. Freedom from CAV for
      all was 79% at 10 years. Fifty-nine patients (18%) developed CAV at a mean of 6.5
      +/- 3 years post-transplant. First year rejections were significantly higher in
      CAV, mean 2.3 vs. 1.4, P = 0.003, odds ratio (OR) 1.8. Rejection with hemodynamic
      compromise beyond 1 year post-transplant was associated with CAV, P < 0.001, OR
      8.4. There was no significant correlation among human leukocyte antigen DR (HLA
      DR) mismatch, pacemaker use or homocysteine levels and the development of CAV.
      Maximum cholesterol and low density lipoprotein (LDL) levels were not
      significantly different. Neither diabetes nor hypertension was significant
      predictors of CAV on multivariate logistic regression analysis. In conclusion,
      frequent and severe rejection episodes may predict pediatric CAV. Neither glucose
      intolerance nor lipid abnormalities appeared to alter risk for CAV in this
      population.

PMID- 16441767
TI  - Association between heat shock protein 70s and toll-like receptor polymorphisms
      with long-term renal allograft survival.
AB  - Long-term renal allograft survival has not improved significantly in recent years
      and only a minority of grafts survives for more than 15 years. To evaluate the
      association between HSPA1A G(190)C, HSPA1B A(1267)G and TLR4 A(299)G
      polymorphisms and allograft survival we analyzed DNA of patients with long-term
      renal graft function over 15 years (Tx15), consecutively transplanted recipients
      (Tx), patients with acute rejection and healthy controls. HSPA1B (1267)AA was
      less prevalent in Tx versus Tx15 (P = 0.02) and versus controls (P = 0.004).
      HSPA1B (1267)GG was more frequent in Tx versus Tx15 (P = 0.005) and versus
      controls (P = 0.002). HSPA1B (1267)G allele occurred more often in Tx versus Tx15
      (P = 0.03), and versus controls (P = 0.02). TLR4 (299)AG genotype prevalence was
      increased in Tx15 versus Tx (P = 0.02), while TLR4 (299)G allele was more
      frequent in Tx15 versus Tx (P = 0.02). The increased frequency of HSPA1B (1267)AA
      and TLR4 (299)AG genotypes in Tx15 group indicates that better cytoprotective
      functions in HSPA1B (1267)AA and reduced proinflammatory response in TLR4 (299)AG
      carriers might have improved renal allograft survival.

PMID- 16441768
TI  - Paediatric kidney transplantation in small children-- a single centre experience.
AB  - Kidney transplantation (KTx) remains a challenging procedure in small children.
      This study presents our centre results. From 1983 to 2004, 40 of 442 paediatric
      KTx were performed in children with a body weight <11 kg. Median body weight was
      9.2 kg (range: 7.2-10.9), median age was 2.7 years (range: 0.9-5.9). Preoperative
      dialysis was performed in 87.5%. In 24 cases (60%) grafts came from cadaveric
      (CAD) and in 16 cases (40%) from living related donors (LRD). Median donor age of
      CAD was 8 years (range: 1-40). The overall 1-, 5-, 10-, 15-year patient survival
      was 93%, 90%, 90% and 87% respectively. The overall 1-, 5-, 10-, 15-year graft
      survival was 90%, 80%, 66% and 56% respectively. There was no significant
      difference in survival of CAD or LRD grafts. Median follow-up was 13.7 years.
      Initial graft function rate was 100% for LRD and 79% for CAD. The relative
      glomerular filtration rate (GFR) showed no statistical difference between CAD and
      LRD. Main reasons for graft loss were chronic transplant nephropathy. Paediatric
      KTx is the treatment of choice even in very small children. Living donor KTx is
      the preferable donor source in terms of primary graft function and timing to
      transplantation.

PMID- 16441769
TI  - Expression of cyclooxygenase-1 and cyclooxygenase-2 in human renal allograft
      rejection-- a prospective study.
AB  - Cyclooxygenases (COX) are known to be involved in inflammatory kidney diseases.
      However, there are no data available about the expression of COX-1 and only
      preliminary reports about the expression of COX-2 in biopsies of patients
      undergoing acute renal allograft rejection. We conducted this prospective study
      to analyze the expression, distribution, and cellular localization of COX-1 and 
      2 and thus to elucidate the role of COX in human kidney transplantation. One
      hundred forty-four biopsies were included from patients without rejection and
      unaltered morphology (n = 60), with acute interstitial rejection (n = 7), with
      acute vascular rejection (n = 21), with chronic allograft nephropathy (n = 16),
      without rejection but with various other lesions (n = 40). COX-1 and -2
      expression was localized in each biopsy by immunohistochemistry. We found a
      highly significant up-regulation of COX-1 in vessels and in infiltrating
      interstitial cells of patients with acute allograft rejection compared with
      biopsies with well-preserved tissue. Also, COX-2 expression was significantly
      elevated in infiltrating interstitial cells of biopsies with acute rejection.
      This is the first prospective study demonstrating a significant induction of both
      COX-1 and -2 in human allograft biopsies with acute rejection after renal
      transplantation.

PMID- 16441770
TI  - Living kidney donors >60 years of age: is it acceptable for the donor and the
      recipient?
AB  - Donors >60 years are now frequently accepted for living kidney transplantation
      (LKT). We asked whether a donor age >60 years may result in a higher risk for
      donor and recipient. All adult LKT from May 1996 to June 2005 were included. Long
      term outcome was analysed, and results were compared for donors >60 and <or=60
      years. Thirty-five grafts were obtained from donors >60 (group A) and 158 from
      donors <or=60 years (group B). In group A 40% and in group B 37% of grafts came
      from unrelated donors (P = 0.769). The mean hospital stay of donors was 8 days in
      group A and 7 days in group B (P = 0.171). The complication rate was 11% in group
      A and 17% in group B (P = 0.409). Following LKT primary graft function was
      observed in 97% in group A and 96% in group B. One- and 5-year graft survival was
      97% and 90% in group A and 99% and 91% in group B. For the first 2 years, mean
      serum creatinine was significantly higher in recipients of group A. Thereafter,
      values were comparable for both groups. As excellent results are achievable using
      living donors >60 years, we suggest that age should no longer be considered as a
      contra-indication for living donation.

PMID- 16441771
TI  - Glycine application and right heart function in a porcine heart transplantation
      model.
AB  - Glycine reduces ischemia-reperfusion injury after experimental liver
      transplantation. We hypothesized that glycine might also protect right heart
      function in an isovolumic cardiac transplantation model. In six domestic donor
      pigs 150 ml of a 300 mmol L-glycine solution were administered intravenously. The
      hearts were then arrested with histidine-tryptophan-ketoglutarate solution.
      Animals without prior glycine infusion served as controls (n = 6). After 4 h of
      ischemia, hearts were transplanted into recipients. An isovolumic model was used
      in which the right ventricular (RV) volume was controlled in vivo using an
      intracavitary high-compliance balloon. After 1 and 2 h of reperfusion the RV
      balloon volume was gradually increased and the developed pressures were recorded
      (P(developed) = P(systolic) - P(diastolic)). Right ventricular failure was
      defined as a decrease in developed intracavitary pressure. Glycine hearts could
      be loaded with a significantly increased volume after 1 h (glycine: 53 +/- 13.7
      ml vs. control: 32 +/- 11.7 ml; P = 0.015) and after 2 h (67 +/- 18.6 ml vs. 43
      +/- 8.2 ml; P = 0.018). Maximal RV developed pressures were not significantly
      different between groups. Postischemic RV end-diastolic compliance was
      significantly higher in glycine-treated animals (P = 0.04). Glycine protects
      early postischemic RV compliance, but has no important influence on maximal
      developed pressures.

PMID- 16441772
TI  - Hyperacute rejection in ex vivo-perfused porcine lungs transgenic for human
      complement regulatory proteins.
AB  - Inhibition of complement activation via human membrane-associated complement
      regulators is known to prevent hyperacute rejection in heart and kidney pig-to
      primate transplantation. The protective effect of such strategies in pulmonary
      xenografts, however, seems to be insufficient. In an ex vivo perfusion, model
      lungs from donor pigs transgenic for human CD55 (n = 6) or human CD59 (n = 5)
      were perfused with fresh human blood and compared with nontransgenic organs (n =
      6). In addition, a soluble complement component 1 esterase inhibitor (C1-Inh) was
      applied in h-CD55 transgenic lungs (n = 3). In the h-CD55 transgenic group,
      survival was prolonged (P < 0.05), quality and maximal time of oxygenation
      significantly improved and pulmonary vascular resistance reduced compared with
      the control group. There was a decreased sequestration of platelets, less
      parenchymal injury and reduced deposition of C(5b-9) in the h-CD55 transgenic
      group. Additional soluble complement inhibition (C1-Inh) did not prolong survival
      of h-CD55 transgenic lungs. Survival and pulmonary function in lungs expressing h
      CD59 was not significantly different from parameters observed in nontransgenic
      lungs. In this ex vivo model of pig-to-primate lung transplantation, membrane
      based complement inhibition resulted in significantly improved pulmonary
      function. However, minor histopathological injuries observed in these transgenic
      xenografts suggested only partial protection from pulmonary dysfunction by
      complement inhibition alone.

PMID- 16441773
TI  - Effect of tacrolimus and partial hepatectomy on transthyretin metabolism in rats.
AB  - Liver transplantation, which serves as treatment of familial amyloidotic
      polyneuropathy (FAP), and domino liver transplantation, which utilizes resected
      livers from patients with FAP for treatment of liver diseases, may induce changes
      in transthyretin (TTR), a pathogenic FAP-related protein. To evaluate this
      possibility, we performed a 70% hepatectomy or administered tacrolimus to Dark
      Agouti (DA) rats for 7 days and then measured changes in liver TTR mRNA levels
      and changes in serum TTR concentrations. After hepatectomy, TTR mRNA levels
      decreased by 77%; at day 3, they returned to preoperative levels. Except for
      slightly elevated serum TTR concentrations 12 h after operation, serum TTR levels
      remained unchanged. Thus, partial hepatectomy did not influence serum TTR
      concentrations. After tacrolimus administration, TTR mRNA declined by 56% 12 h
      after the experiment started; however, after day 3, a rebound phenomenon occurred
      until day 7. Tacrolimus may facilitate serum TTR degradation, although production
      of TTR in the liver also increased. This finding -- that TTR, the source of FAP
      inducing amyloid, did not increase after transplantation -- may help post
      transplantation treatment of patients who have FAP and other liver diseases.

PMID- 16441775
TI  - Sirolimus in de novo heart transplant recipients with severe renal impairment.
AB  - Two patients with end-stage heart failure and advanced renal dysfunction (under
      chronic dialysis therapy) underwent heart transplantation. In order to avoid
      further renal impairment, a calcineurine inhibitor-free immunosuppression regimen
      based on the sirolimus was used. Although temporary perioperative support with
      hemofiltration and dialysis was needed, both patients eventually regained a
      reasonable renal function with no episodes of clinical rejection and normal
      cardiac function at 13 and 11 months, respectively, after transplantation.
      Sirolimus-based immunosuppression might be an interesting alternative to
      calcineurine inhibitors in the management of patients with significant renal
      impairment.

PMID- 16441774
TI  - Heart transplantation across the antibodies against HLA and ABO.
AB  - We have intentionally performed heart transplantation in a 5-year-old child,
      despite the most unfavourable risk factors for patient survival; the presence of
      high level of antibodies against donor's human leucocyte antigen (HLA) class I/II
      and blood group antigens. Pretransplant treatment by mycophenolate mofetil,
      prednisolone, tacrolimus, intravenous immunoglobulin, rituximab, protein-A
      immunoadsorption (IA) and plasma exchange reduced antibody titres against the
      donor's lymphocytes from 128 to 16 and against the donor's blood group antigen
      from 256 to 0. The patient was urgently transplanted with a heart from an ABO
      incompatible donor (A(1) to O). A standard triple-drug immunosuppressive protocol
      was used. No hyperacute rejection was seen. Antibodies against the donor's HLA
      antigens remained at a low level despite three acute rejections. Rising anti-A(1)
      blood group antibodies preceded the second rejection and were reduced by two
      blood group-specific IAs and remained at a low level. The patient is doing well
      despite the persistence of donor-reactive antibodies.

PMID- 16441776
TI  - Long-term survival after isolated liver transplantation for intrahepatic biliary
      papillomatosis.

PMID- 16441777
TI  - Staff training to deal with bereaved relatives in intensive care-- conclusion of
      11 years and 874 workshops of the European Donor Hospital Education Programme in
      Germany.

PMID- 16441778
TI  - The use of partial splenic artery embolization made it possible to administer
      interferon and ribavirin therapy in a liver transplant patient with fibrosing
      cholestatic hepatitis C complicated with thrombocytopenia.

PMID- 16441779
TI  - Comparison of bacterial plaque samples from titanium implant and tooth surfaces
      by different methods.
AB  - Studies have shown similarities in the microflora between titanium implants or
      tooth sites when samples are taken by gingival crevicular fluid (GCF) sampling
      methods. The purpose of the present study was to study the microflora from
      curette and GCF samples using the checkerboard DNA-DNA hybridization method to
      assess the microflora of patients who had at least one oral osseo-integrated
      implant and who were otherwise dentate. Plaque samples were taken from
      tooth/implant surfaces and from sulcular gingival surfaces with curettes, and
      from gingival fluid using filter papers. A total of 28 subjects (11 females) were
      enrolled in the study. The mean age of the subjects was 64.1 years (SD+/-4.7). On
      average, the implants studied had been in function for 3.7 years (SD+/-2.9). The
      proportion of Streptococcus oralis (P<0.02) and Fusobacterium periodonticum
      (P<0.02) was significantly higher at tooth sites (curette samples). The GCF
      samples yielded higher proportions for 28/40 species studies (P-values varying
      between 0.05 and 0.001). The proportions of Tannerella forsythia (T.
      forsythensis), and Treponema denticola were both higher in GCF samples (P<0.02
      and P<0.05, respectively) than in curette samples (implant sites). The microbial
      composition in gingival fluid from samples taken at implant sites differed partly
      from that of curette samples taken from implant surfaces or from sulcular soft
      tissues, providing higher counts for most bacteria studied at implant surfaces,
      but with the exception of Porphyromonas gingivalis. A combination of GCF and
      curette sampling methods might be the most representative sample method.

PMID- 16441780
TI  - Early colonization of non-submerged dental implants in patients with a history of
      advanced aggressive periodontitis.
AB  - The aim of the study was to evaluate the early colonization of non-submerged
      implants over a 6-month period in partially edentulous patients treated for
      advanced aggressive periodontal disease. In 22 patients treated for advanced
      aggressive periodontitis and in a supportive maintenance program for a period
      between 12 and 240 months at implant surgery, a total of 68 non-submerged dental
      implants were installed. Patients had a plaque score below 20%, and less than 20%
      of the pockets around the teeth were bleeding on probing (BOP). Using DNA-probes
      (micro-IDent), the presence and concentration of five periodontal pathogens
      (Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg),
      Prevotella intermedia (Pi), Tannerella forsythensis (Tf) and Treponema denticola
      (Td)) were determined in the five deepest pockets of the rest dentition pre
      operatively and after 6 months as well as five places around each implant 10
      days, 1 month, 3 months and 6 months after surgery. In each patient, a test to
      determine the genotype interleukin-1 (IL-1) was performed (PST - micro-IDent).
      After 6 months, no difference in microbial composition as compared with baseline
      was found around the teeth in five patients, in 12 minute differences and in five
      patients important differences were observed. Ten days after surgery, three
      patients had a complete similar bacterial composition between teeth and implants.
      In 14 patients, the composition was fairly similar, while large differences in
      composition and concentration occurred in five patients. This microbiota around
      the implants remained almost unchanged over a 6-month period and did not hamper
      the clinical and radiographic osseointegration and did not lead to peri
      implantitis, mucositis or initiation of bone destruction.

PMID- 16441781
TI  - Comparisons of bacterial patterns present at implant and tooth sites in subjects
      on supportive periodontal therapy. I. Impact of clinical variables, gender and
      smoking.
AB  - OBJECTIVE: (I) To compare the oral microflora at implant and tooth sites in
      subjects participating in a periodontal recall program, (II) to test whether the
      microflora at implant and tooth sites differ as an effect of gingival bleeding
      (bleeding on probing (BOP)), or pocket probing depth (PPD), and (III) to test
      whether smoking and gender had an impact on the microflora. MATERIAL AND METHODS:
      Data were collected from 127 implants and all teeth in 56 subjects.
      Microbiological data were identified by the DNA-DNA checkerboard hybridization.
      RESULTS: PPD> or =4 mm were found in 16.9% of tooth, and at 26.6% of implant
      sites (P<0.01). Tooth sites with PPD> or =4 mm had a 3.1-fold higher bacterial
      load than implant sites (mean difference: 66%, 95% confidence interval (CI): 40.7
      91.3, P<0.001). No differences were found for the red, orange, green, and yellow
      complexes. A higher total bacterial load was found at implant sites with PPD> or
      =4 mm (mean difference 35.7 x 10(5), 95% CI: 5.2 (10(5)) to 66.1 (10(5)), P<0.02
      with equal variance not assumed). At implant sites, BOP had no impact on
      bacterial load but influenced the load at tooth sites (P<0.01). CONCLUSION: BOP,
      and smoking had no impact on bacteria at implant sites but influenced the
      bacterial load at tooth sites. Tooth sites harbored more bacteria than implant
      sites with comparable PPD. The 4 mm PPD cutoff level influenced the distribution
      and amounts of bacterial loads. The subject factor is explanatory to bacterial
      load at both tooth and implant sites.

PMID- 16441782
TI  - Dynamics of initial subgingival colonization of 'pristine' peri-implant pockets.
AB  - BACKGROUND: Periodontitis and peri-implantitis are linked to the presence of
      several key pathogens. The treatment of these infectious processes therefore
      involves the reduction/eradication of bacteria associated with periodontitis.
      METHODS: This prospective, split-mouth, single-blind study followed the
      colonization of 'pristine' sulci created in 42 partially edentulous patients
      during implant surgery (e.g. abutment connection). The hypothesis was that the
      composition of the maturing subgingival plaque in these 'fresh' peri-implant
      pockets would soon (within 2 weeks) be comparable to the subgingival microbiota
      of teeth with similar clinical parameters (reference sites), including the
      presence of bacteria associated with periodontitis. Per patient, four subgingival
      plaque samples were taken from shallow and medium pockets around implants (test
      sites), and teeth within the same quadrant (undisturbed microbiota as control
      sites), 1, 2, 4, 13, 26 and 78 weeks after abutment connection, respectively. The
      samples were analysed by either checkerboard DNA-DNA hybridization, or cultural
      techniques, or real-time polymerase chain reaction (PCR) for intra-subject
      comparisons (teeth vs. implant, for comparable probing depths). RESULTS:
      Checkerboard DNA-DNA hybridization and real-time PCR revealed a complex
      microbiota (including several pathogenic species) in the peri-implant pockets
      within 2 weeks after abutment connection. After 7 days, the detection frequency
      for most species (including the bacteria associated with periodontitis) was
      already nearly identical in samples from the fresh peri-implant pockets (5% and
      20% of the microbiota belonging to red and orange complex, respectively) when
      compared with samples from the reference teeth. Afterwards (e.g. between weeks 2
      and 13), the number of bacteria in peri-implant pockets only slightly increased
      (+/-0.1 log value), with minor changes in the relative proportions of bacteria
      associated with periodontitis (8% and 33% of the microbiota belonging to red and
      orange complex, respectively). Although small differences were seen between teeth
      and implants at week 2 with cultural techniques, a striking similarity in
      subgingival microbiota was found with this technique from month 3 on, with nearly
      identical detection frequencies for bacteria associated with periodontitis for
      both abutment types. CONCLUSIONS: This study indicates that the initial
      colonization of peri-implant pockets with bacteria associated with periodontitis
      occurs within 2 weeks.

PMID- 16441783
TI  - Cyclooxygenase-2 inhibition selectively attenuates bone morphogenetic protein-6
      synthesis and bone formation during guided tissue regeneration in a rat model.
AB  - OBJECTIVES: Bone formation during guided tissue regeneration is a tightly
      regulated process involving cells, extracellular matrix and growth factors. The
      aims of this study were (i) to examine the expression of cyclooxygenase-2 (COX-2)
      during bone regeneration and (ii) the effects of selective COX-2 inhibition on
      osseous regeneration and growth factor expression in the rodent femur model.
      MATERIAL AND METHODS: A standardized transcortical defect of 5 x 1.5 mm was
      prepared in the femur of 12 male rats and a closed half-cylindrical titanium
      chamber was placed over the defect. The expression of COX-2 and of platelet
      derived growth factor-B (PDGF-B), bone morphogenetic protein-6 (BMP-6) and
      insulin-like growth factor-I/II (IGF-I/II) was analyzed at Days 3, 7, 21 and 28
      semiquantitatively by reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. The effects of COX-2 inhibition by intraperitoneal
      injection of NS-398 (3 mg/kg/day) were analyzed in five additional animals
      sacrificed at Day 14. RESULTS: Histomorphometry revealed that new bone formation
      occurred in the cortical defect area as well as in the supracortical region, i.e.
      region within the chamber by Day 7 and increased through Day 28.
      Immunohistochemical evidence of COX-2 and PDGF-B levels were observed early (i.e.
      Day 3) and decreased rapidly by Day 7. BMP-6 expression was maximal at Day 3 and
      slowly declined by Day 28. In contrast, IGF-I/II expression gradually increased
      during the 28-day period. Systemic administration NS-398 caused a statistically
      significant reduction (P<0.05) in new bone formation (25-30%) and was associated
      with a statistically significant reduction in BMP-6 protein and mRNA expression
      (50% and 65% at P<0.05 and P<0.01, respectively). PDGF-B mRNA or protein
      expression was not affected by NS-398 treatment. CONCLUSION: COX-2 inhibition
      resulted in reduced BMP-6 expression and impaired osseous regeneration suggesting
      an important role for COX-2-induced signaling in BMP synthesis and new bone
      formation.

PMID- 16441784
TI  - Effects of Delta12-prostaglandin J2 on bone regeneration and growth factor
      expression in rats.
AB  - OBJECTIVES: Cyclopentenone prostaglandins have been shown to promote osteoblast
      differentiation in vitro. The aim of this study was to examine in a rat model the
      effects of local delivery of Delta(12)-prostaglandin J(2) (Delta(12)-PGJ(2)) on
      new bone formation and growth factor expression in (i) cortical defects and (ii)
      around titanium implants. MATERIAL AND METHODS: Standardized transcortical
      defects were prepared bilaterally in the femur of 28 male Wistar rats. Ten
      microliters of Delta(12)-PGJ(2) at 4 concentrations (10(-9), 10(-7), 10(-5) and
      10(-3) mol/l) in a collagen vehicle were delivered inside a half-cylindrical
      titanium chamber fixed over the defect. Contralateral defects served as vehicle
      controls. Ten days after surgery, the amount of new bone formation in the
      cortical defect area was determined by histomorphometry and expression of
      platelet-derived growth factor (PDGF)-A and -B, insulin-like growth factor (IGF)
      I/II, bone morphogenetic protein (BMP)-2 and -6 was examined by
      immunohistochemistry. In an additional six rats, 24 titanium implants were
      inserted into the femur. Five microliters of carboxymethylcellulose alone
      (control) or with Delta(12)-PGJ(2) (10(-5) and 10(-3) mol/l) were delivered into
      surgically prepared beds prior to implant installation. RESULTS: Delta(12)-PGJ(2)
      (10(-5) and 10(-3) mol/l) significantly enhanced new bone formation (33%, P<0.05)
      compared with control cortical defects. Delivery of Delta(12)-PGJ(2) at 10(-3)
      mol/l significantly increased PDGF-A and -B and BMP-2 and -6 protein expression
      (P<0.05) compared with control defects. No significant difference was found in
      IGF-I/II expression compared with controls. Administration of Delta(12)-PGJ(2)
      also significantly increased endosteal new bone formation around implants
      compared with controls. CONCLUSION: Local delivery of Delta(12)-PGJ(2) promoted
      new bone formation in the cortical defect area and around titanium implants.
      Enhanced expression of BMP-2 and -6 as well as PDGF-A and -B may be involved in
      Delta(12)-PGJ(2)-induced new bone formation.

PMID- 16441785
TI  - Permucosal implants combined with iliac crest onlay grafts used in extreme
      atrophy of the mandible: long-term results of a prospective study.
AB  - Thirteen patients received an onlay bone-graft augmentation to their severely
      atrophic mandible in combination with simultaneous implant insertion. This
      treatment modality was studied in a long-term prospective clinical and
      radiographic study. A reproducible measurement method, consisting of oblique
      lateral cephalometric radiographs, in combination with an image analysis system,
      was used to accurately assess the graft resorption rate. On average, 51% (95%
      confidence interval 42-61%) of the grafted bone height remained after 10-11
      years. Resorption of the graft occurred mainly during the first years and showed
      a marked degree of individual variance. In the following years, the resorption
      rate followed a predictable pattern in most of our patients. Ventral and dorsal
      sites exhibited a similar degree of resorption. Peri-implantitis occurred in nine
      patients. Ten muco-gingival surgical interventions were necessary in four of
      these nine patients. No implants were lost and 12 patients indicated that they
      were satisfied. It is concluded that the described surgical technique should be
      used on stringent indication only, and alternative techniques are discussed.

PMID- 16441786
TI  - Analysis of bone-implant interaction phenomena by using a numerical approach.
AB  - OBJECTIVES: The purpose of the present work is to investigate the interaction
      phenomena occurring between endosseus dental implants and peri-implant bone
      tissue. MATERIAL AND METHODS: Detailed finite element models are adopted in order
      to analyze the actual behavior of bone-implant system depending on implant and
      anatomical site configuration and loading conditions. Different types of titanium
      dental implants are considered. Implant finite element models are obtained
      through a reverse engineering procedure and adopting specific software for the
      reconstruction of geometrical configuration. Anatomical sites are modeled
      starting from computerized tomography data, according to specific image
      processing procedures. RESULTS: Occlusal static forces are applied to the
      implants and their effects on the bone-implant interface region are evaluated.
      The influence of several parameters, such as morphometry of anatomical site or
      loading condition, on the biomechanical response of bone-implant system is
      considered. CONCLUSIONS: The evaluation of the biomechanical response of implant
      bone compound necessarily requires the adoption of accurate numerical models,
      accounting for the complex geometry of threaded implants, as well as of the
      anatomy of the patients to be able to provide for reliable results pertaining to
      stress/strain path on peri-implant bone tissue.

PMID- 16441787
TI  - Resonance frequency analysis and damping capacity assessment. Part I: an in vitro
      study on measurement reliability and a method of comparison in the determination
      of primary dental implant stability.
AB  - OBJECTIVES: The aims of this in vitro study were to evaluate reliability of the
      Osstell and Periotest devices in the assessment of implant stability and to
      perform a method comparison. MATERIAL AND METHODS: Commercial dental implants
      were inserted into bovine rib segments of different anatomical origins and
      densities. Repeated measurements were performed, varying (a) the torque-in force
      of the devices' attachment screw (the Osstell transducer and the ball attachment,
      insert for the Periotest device), (b) the insertion site bone quality, and (c)
      the thread exposure in simulated peri-implant bone defects. RESULTS: Both methods
      were comparably reliable and showed a strong association to each other in the
      classification of implant stability. As opposed to torque-forced screw
      attachment, the variations in bone composition, differences in inter-implant
      stability of adjacent implants, and peri-implant bone reduction were
      statistically significant for both methods. CONCLUSIONS: Both non-invasive
      diagnostic devices seem to be useful in the long-term follow-up of implant
      integration.

PMID- 16441788
TI  - Resonance frequency analysis and damping capacity assessment. Part 2: peri
      implant bone loss follow-up. An in vitro study with the Periotest and Osstell
      instruments.
AB  - OBJECTIVE: We compared the performance of damping capacity assessment (Periotest
      device) to resonance frequency analysis (Osstell device) in the assessment of
      peri-implant bone loss in an in vitro experiment. MATERIAL AND METHODS: Screw
      type oral implants were polymerized into acrylic blocks. Peri-implant bone loss
      was simulated by successively removing defined portions of material surrounding
      the implants in millimeter increments. Measurement values of both devices were
      compared by assessing the associated measurement errors, by calculating
      correlation analyses and drawing scatterplots, and by means of regression
      analysis referring to increasing bone loss. RESULTS: Both devices produced
      comparable results suggesting agreement of the measured implant stability values
      to the actual loss of peri-implant resin. There was a noticeable correlation of
      the Periotest and Osstell implant stability values. CONCLUSION: The results of
      this experiment suggest agreement in predicting the actual implant stability with
      both the instruments with the Osstell instrument being the more precise device.

PMID- 16441789
TI  - A distinguishable observation between survival and success rate outcome of
      hydroxyapatite-coated implants in 5-10 years in function.
AB  - PURPOSE: To differentiate between the survival and success definitions of
      functional hydroxyapatite (HA)-coated implant prosthesis. METHODS: A total of 248
      implants (62 patients), 5-10 years in function, were evaluated. The implant
      distribution length was 8 mm (6.5%), 10 mm (29.4%), 13 mm (30.2%) and 15 mm
      (33.9%). The diameter was 3.25 mm (60.1%) and 4 mm (39.9%). Probing depth (PD),
      gingival index (GI), height of keratinized mucosa (KM) and recession (REC) were
      measured. Periapical radiographs were taken to estimate the amount of crestal
      bone resorption (BL), mesially and distally, with the aid of a millimetric-scaled
      magnifying glass (x 8). Only implants that fulfilled the success rate criteria
      were considered as successful. All other functional implants were assigned to the
      non-successful group. All functional implant prostheses were defined as survival
      ones. RESULTS: The accumulative survival rate after 5 and 10 years was 94.4% and
      92.8%, respectively. Accumulative success rates were 89.9% and 54%, respectively.
      Implants 13 and 15 mm in length (97.9% and 96.4%, respectively) had the highest
      survival rate, which was higher over implants 8 and 10 mm in length (75%, P<0.01
      and 88.2%, respectively). The survival rate of 4 mm diameter implants compared
      with 3.25 mm was 96.5% and 90.3%, respectively (P=0.019). The average BL was 1.7,
      0.92 and 2.79 mm for the survival, successful and non-successful defined implant
      groups. PD was 3.26, 2.79 and 4 mm and GI was 0.96, 0.75 and 1.57, respectively.
      These measurements were statistically different between implant groups. KM and
      REC measurements showed similar scoring for all groups. A correlation was shown
      between successful and non-successful implants on the score of GI and PD (P<0.001
      in both). CONCLUSION: A distinguishable observation between survival and success
      rate was noted particularly in long-term observations. Implant length and
      diameter have an influence on the survival rate. Clinical parameter scores
      expressed an influence on the defined implant status.

PMID- 16441790
TI  - Prosthetic treatment of maxillary lateral incisor agenesis with osseointegrated
      implants: a 24-39-month prospective clinical study.
AB  - OBJECTIVES: The present study aimed at evaluating the marginal bone resorption
      and the peri-implant tissue conditions around Narrow-Neck ITI implants in the
      implant-prosthetic treatment of the agenesis of maxillary lateral incisors.
      MATERIAL AND METHODS: Thirty patients affected by monolateral or bilateral
      agenesis of the maxillary lateral incisors were selected. Thirty-four ITI-SLA
      Narrow Neck implants were inserted and loaded about 4 months after the surgical
      procedure. The final restorations were realized using Aureo Galvan Crowns
      veneered with feldspathic ceramics. The follow-up period ranged from 24 to 39
      months. Both marginal bone resorption and soft tissue quality were evaluated. The
      data were statistically analysed using analysis of variance (ANOVA) for repeated
      measures, one-way ANOVA and Tukey's post hoc test (P=0.05). RESULTS: During the
      24-39-month follow-up period, no implant showed either pain and sensitivity or
      mobility. After 39 months of functional loading, a cumulative survival rate of
      97.06% and a cumulative success rate of 94.12% were calculated. CONCLUSIONS: In
      case of maxillary lateral incisor agenesis, the implant-prosthetic approach has
      proved to be a reliable and predictable treatment for both re-establishment of
      function and aesthetics. Satisfactory values of marginal bone resorption over
      time and optimal conditions of peri-implant tissue around Narrow-Neck ITI
      implants were found.

PMID- 16441791
TI  - Maxillary sinus floor grafting with beta-tricalcium phosphate in humans: density
      and microarchitecture of the newly formed bone.
AB  - OBJECTIVES: Graft insertion can effectively enhance the regeneration of
      debilitated bone. The effects of an alloplastic bone-replacing material, beta
      tricalcium phosphate (Cerasorb), and of autogenous bone graft were compared.
      MATERIALS AND METHODS: In 17 edentulous patients, the maxillary sinus floor was
      extremely atrophied to such an extent that implant placement was impossible. The
      Schneiderian membrane was surgically elevated bilaterally by insertion of
      Cerasorb (experimental side) and autogenous bone graft (control side). After
      surgery, the recovery was followed clinically and radiologically. After 6 months,
      68 bone cylinders were excised from the grafted areas and implants were inserted
      into their places. The bone samples were embedded into resin, and the
      osteointegration of the grafts was studied histologically. Trabecular bone volume
      (TBV) and trabecular bone pattern factor (TBPf) were quantified by
      histomorphometry. RESULTS: Cerasorb proved to be an effective bone-replacing
      material with osteoconductivity; it was capable of gradual disintegration,
      thereby providing space for the regenerating bone. The new bone density was not
      significantly different on the experimental and control sides (32.4+/-10.9% and
      34.7+/-11.9%, respectively). However, the graft biodegradation was significantly
      slower on the experimental side than the control side. The TBPf value was lower
      on the control side than on the experimental side (-0.53+/-1.7 and -0.11+/-1.4
      mm(-1), respectively), but this difference was not significant. CONCLUSIONS: Six
      months after insertion of the grafts, the bone of the augmented sinus floor was
      strong and suitable for anchorage of dental implants, irrespective of whether
      autogenous bone or Cerasorb particles had been applied.

PMID- 16441792
TI  - Recommended placement torque when tightening an orthodontic mini-implant.
AB  - To determine an adequate placement torque for obtaining a better success rate of
      mini-implants that are screwed into the buccal alveolar bone of the posterior
      region as an anchor for orthodontic treatment, implant placement torque (IPT) was
      measured. The subjects were 41 orthodontic patients (124 implants), with an
      average age of 24.9 years (SD 6.5 years), who had surgery to place titanium mini
      implants. The peak value of IPT was measured using a torque screwdriver. The
      success rate of the mini-implant anchor for 124 implants was 85.5%. The mean IPT
      ranged from 7.2 to 13.5 N cm, depending on the location of the implants. There
      was a significant difference in the IPT between maxilla and mandible. The IPT in
      the mandible was, unexpectedly, significantly higher in the failure group than in
      the success group. Therefore, a large IPT should not be used always. According to
      our calculations of the risk ratio for failure, to raise the success rate of 1.6
      mm diameter mini-implants, the recommended IPT is within the range from 5 to 10 N
      cm.

PMID- 16441793
TI  - Otology and audiology in the UK: isolated or integrated practice?

PMID- 16441794
TI  - The evidence base for the application of contralateral bone anchored hearing aids
      in acquired unilateral sensorineural hearing loss in adults.
AB  - . Acquired unilateral sensorineural hearing loss reduces the ability to localize
      sounds and to discriminate in background noise. . Four controlled trials attempt
      to determine the benefit of contralateral bone anchored hearing aids over
      contralateral routing of signal (CROS) hearing aids and over the unaided
      condition. All found no significant improvement in auditory localization with
      either aid. Speech discrimination in noise and subjective questionnaire measures
      of auditory abilities showed an advantage for bone anchored hearing aid (BAHA) >
      CROS > unaided conditions. . All four studies have material shortfalls: (i) the
      BAHA was always trialled after the CROS aid; (ii) CROS aids were only trialled
      for 4 weeks; (iii) none used any measure of hearing handicap when selecting
      subjects; (iv) two studies have a bias in terms of patient selection; (v) all
      studies were underpowered (vi) double reporting of patients occurred. . There is
      a paucity of evidence to support the efficacy of BAHA in the treatment of
      acquired unilateral sensorineural hearing loss. Clinicians should proceed with
      caution and perhaps await a larger randomized trial. . It is perhaps only
      appropriate to insert a BAHA peg at the time of vestibular schwanoma tumour
      excision in patients with good preoperative hearing, as their hearing handicap
      increases most.

PMID- 16441795
TI  - Do chronic changes in nasal airflow have any physiological or pathological effect
      on the nose and paranasal sinuses? A systematic review.
AB  - .A reduction in nasal airflow associated with anatomical defects of the nose such
      as nasal septal deviation has been proposed to cause nasal pathology. . The
      majority of animal experiments where one nasal passage is surgically closed over
      several months report only minor changes in the histology of the nasal epithelium
      and no rhinitis or sinusitis. .Complete abolition of nasal airflow associated
      with laryngectomy or the treatment of atrophic rhinitis is not associated with
      the development of rhinitis or sinusitis. . Radiological studies have shown a
      lack of association between the degree of nasal septal deviation and evidence of
      rhinosinusitis. .Such studies provide evidence that reduced nasal airflow causes
      no significant nasal disease. . There is no convincing evidence that a reduction
      in nasal airflow is a causative factor for rhinitis or sinusitis.

PMID- 16441796
TI  - A systematic review of the role of proton pump inhibitors for symptoms of
      laryngopharyngeal reflux.
AB  - . Proton pump inhibitors are currently used widely for the treatment of
      laryngopharyngeal reflux. . This systematic review assessed the efficacy of
      proton pump inhibitors in the treatment of symptoms of laryngopharyngeal reflux.
      . Outcome measures used to assess efficacy of proton pump inhibitors included
      endoscopic laryngeal signs and pH recordings. .Only two small randomized
      controlled trials included patients with objective evidence of reflux in the 24-h
      ambulatory oesophageal pH monitoring. . Pooled analysis of these two randomized
      controlled trials failed to show any effect in favour of treatment with proton
      pump inhibitors. .Further randomized-controlled trials are required to ascertain
      the role of proton pump inhibitors in the treatment of laryngopharyngeal reflux.

PMID- 16441798
TI  - A randomized trial of Rapid Rhino Riemann and Telfa nasal packs following
      endoscopic sinus surgery.
AB  - OBJECTIVES: To compare Telfa with the Rapid Rhino Riemann nasal pack for use
      following endoscopic sinus surgery. DESIGN: Prospective, randomized, double
      blind, paired trial. SETTING: Tertiary otolaryngology hospital. PARTICIPANTS:
      Forty-five adult patients undergoing bilateral endoscopic sinus surgery for
      either chronic rhinosinusitis or nasal polyps. MAIN OUTCOME MEASURES: A visual
      analogue scale was used to assess discomfort caused by the presence of the packs
      in the nose and by their removal. The amount of bleeding was noted with the packs
      in place and following their removal. Crusting and adhesions were assessed 2 and
      6 weeks following surgery. RESULTS: Both packs performed well giving good
      haemostasis and causing little bleeding on removal. Both packs caused only mild
      discomfort while in the nose. On the visual analogue scale of 0-10 cm the mean
      visual analogue score for Rapid Rhino Riemann pack was 1.7 and for Telfa 2.0 (P =
      0.371). The Rapid Rhino Riemann pack caused significantly less pain on removal
      compared with the Telfa pack with a mean visual analogue score of 2.0 in
      comparison with 3.7 for Telfa (P = 0.001). There were less adhesions with the
      Rapid Rhino Riemann than Telfa pack but this was not statistically significant (P
      = 0.102). CONCLUSIONS: Both Telfa and Rapid Rhino Riemann packs can be
      recommended as packs that control postoperative haemorrhage, do not cause
      bleeding on removal and cause little discomfort while in the nose. The Rapid
      Rhino Riemann pack has the advantage of causing significantly less pain on
      removal.

PMID- 16441799
TI  - Topical anaesthesia before nasendoscopy: a randomized controlled trial of co
      phenylcaine compared with lignocaine.
AB  - OBJECTIVE: To evaluate the relative effectiveness of co-phenylcaine (lignocaine
      5% with phenylephrine) and lignocaine 5% sprays when administered prior to rigid
      nasendoscopy. DESIGN: Randomized, double blind controlled study. SETTING:
      Teaching hospital otolaryngology unit. PARTICIPANTS: Thirty patients requiring
      routine outpatient rigid nasendoscopy were administered five puffs of either co
      phenylcaine or lignocaine 5% spray which had been randomly assigned to either the
      first or the second visit. Ten minutes later nasendoscopy was performed.
      Immediately after nasendoscopy the ease of performance of the procedure and the
      quality of the view achieved was rated on a visual analogue scale by the
      endoscopist and the patients recorded the level of pain experienced on a visual
      analogue scale. Two weeks later, the patients returned for a repeat nasendoscopy,
      receiving the alternate spray. MAIN OUTCOMES MEASURES: Ease of performance and
      quality of view of achieved by endoscopists and pain experienced by patients,
      both measured with visual analogue scales. RESULTS: The ease of passage of the
      endoscope and quality of the view obtained was found to be greater after the
      administration of co-phenylcaine [visual analogue scores 84 (95% CI: 80-89) than
      after lignocaine and 77 (95% CI: 73-81) (P < 0.01)]. The two sprays produced
      similar levels of topical anaesthesia. CONCLUSIONS: Nasendoscopy can be performed
      with minimal discomfort after the administration of either co-phenylcaine or
      lignocaine 5% sprays. The vasoconstricting action of co-phenylcaine increases the
      ease of passage of the endoscope and quality of the view obtained by the
      endoscopist.

PMID- 16441800
TI  - Use of intravenous steroids at induction of anaesthesia for adult tonsillectomy
      to reduce post-operative nausea and vomiting and pain: a double-blind randomized
      controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of intravenous steroids at induction of
      anaesthetic to reduce post-operative nausea and vomiting and pain after adult
      tonsillectomy. DESIGN: Prospective, double-blind, randomized, placebo controlled
      trial, with ethical approval, following Consolidated Standards of Reporting
      Trials guidelines. SETTING: District General Hospital in Scotland, UK.
      PARTICIPANTS: Seventy-two adults between 16 and 70 years, American Association of
      Anaethetists (ASA) 1, listed for elective tonsillectomy. INTERVENTION: Single
      dose of either 10 mg of dexamethasone or 2 mL of saline after induction with a
      consistent anaesthetic technique. MAIN OUTCOME MEASURES: Patients filled in a
      visual analogue scale relating to pain and post-operative nausea and vomiting for
      the day of operation and 7 days after operation. The time to first ingestion of
      food and drink after operation was also noted. RESULTS: Data completion rate of
      64% (46 of 72 patients enrolled). Statistically significant relative decrease
      (62%P = 0.001) in the incidence of post-operative nausea and vomiting was seen in
      those treated with dexamethasone. Statistically significant relative decrease
      (23%P = 0.016) in post-operative pain scores for the day of operation was seen in
      those treated with dexamethasone. Significant decrease (17.5%, P < 0.001) in mean
      pain score for seven post-operative days was seen in those treated with
      dexamethasone. No adverse effects were seen. CONCLUSIONS: Dexamethasone given as
      a single dose of 10 mg at induction of anaesthesia for adult tonsillectomy is an
      effective, safe and inexpensive method for reducing morbidity in adult
      tonsillectomy.

PMID- 16441801
TI  - Tonsil size and body mass index are important factors for efficacy of simple
      tonsillectomy in obstructive sleep apnoea syndrome.
AB  - OBJECTIVES: To evaluate the efficacy of simple tonsillectomy to treat obstructive
      sleep apnoea syndrome (OSAS) in adults. DESIGN: Prospective study. SETTING:
      Tertiary referral centre. PARTICIPANTS: Thirty patients (28 males) underwent
      simple tonsillectomy under general anaesthesia. The patients' mean age was 33.2
      +/- 6.8 years and body mass index was 30.7 +/- 6.0 kg/m2. Seven patients (23%)
      were classified with grade 4, 16 patients (53%) with grade 3, and seven patients
      (23%) with grade 2 according to the tonsil size of Friedman's classification.
      MAIN OUTCOME MEASURES: The number of apnoea episodes per hour (apnoea index), the
      number of apnoea and hypopnoea episodes per hour (apnoea-hypopnoea index), lowest
      nocturnal oxygen saturation and oxygen desaturation time were measured during
      overnight polysomnography before and after surgery. A successful tonsillectomy
      was defined as an apnoea-hypopnoea index improvement ratio of > or =50% and an
      apnoea-hypopnoea index <20 after operation. RESULTS: Apnoea-hypopnoea index
      decreased from 69.0 +/- 28.4/h to 30.1 +/- 24.0/h (P < 0.0001). Simple
      tonsillectomy was successful in all six patients with body mass index <25 kg/m2.
      Concerning success rate of simple tonsillectomy with tonsil, size 2 was lowest
      (42.9%). Eight of the 13 patients who used continuous positive airway pressure
      before simple tonsillectomy did not use continuous positive airway pressure after
      simple tonsillectomy because of a significant reduction of excessive daytime
      sleepiness. Continuous positive airway pressure decreased significantly after
      simple tonsillectomy from 13.6 +/- 2.5 cmH2O preoperatively to 10.6 +/- 1.3 cmH2O
      postoperatively (P < 0.05). CONCLUSIONS: These data suggest that simple
      tonsillectomy is a beneficial modality to treat OSAS in selected patients (larger
      tonsil, low body mass index), even in adults.

PMID- 16441802
TI  - Acoustic parameters of snoring sound to compare natural snores with snores during
      'steady-state' propofol sedation.
AB  - OBJECTIVES: To investigate the acoustic similarity between natural and sedation
      induced snores. DESIGN: Prospective observational study. SETTING: University
      Hospital Aintree, Liverpool, UK. PARTICIPANTS: Twenty-one patients, who had
      already had overnight snore recordings, completed a pre-operative sleep
      nasendoscopic examination. Endoscopic examination of the upper aero-digestive
      tract was performed at sequentially increasing, steady-state sedation levels,
      using intravenous propofol administered according to a weight/time-based
      algorithm to predict blood and effect site (tissue) concentrations. At each
      sedation level at which snoring occurred, snoring sound was recorded. From these
      samples, snore files, comprising the inspiratory sound of each snore were
      created. Similarly, from natural snores recorded pre-operatively, snore files,
      comprising the inspiratory sounds of the first 100 snores with the patient
      sleeping in a supine position, were also created. MAIN OUTCOME MEASURES: Snore
      duration (s), loudness (dBA), periodicity (%) and energy ratios for the frequency
      sub-bands 0-200, 0-250 and 0-400 Hz. RESULTS: Snore loudness increased
      significantly (P < 0.0001), whilst energy ratios for frequency bands 0-200, 0-250
      and 0-400 Hz all decreased significantly as sedation level increased (P < 0.001).
      A significant difference between natural snoring and snoring induced at the
      lowest sedation level was shown (P < 0.0001). Endoscopic examination was not
      tolerated at this sedation level. CONCLUSIONS: The acoustic characteristics of
      sedation-induced and natural snores are sufficiently different to recommend the
      need for further research to determine whether the technique of sleep
      nasendoscopy is, in fact, a valid predictor of outcome of snoring surgery.

PMID- 16441804
TI  - Case reports can be informative.

PMID- 16441805
TI  - How we do it: patient participation in cochlear implant selection.
AB  - . Involving patients and parents in the choice of their cochlear implant
      encourages an active role in the process and facilitates 'bonding' and
      'ownership' of the device. . The most frequent reasons given by patients for
      selecting a device included cochlear implant comfort and appearance. . We
      describe the Implant Programme based at the Royal National Throat, Nose and Ear
      Hospital, London, and also examine patient satisfaction with the scheme.

PMID- 16441806
TI  - How we do it: the Owa (Addenbrookes) grommet.
AB  - . Grommet insertion is one of the most common procedures performed under general
      anaesthesia. . The authors describe an innovative grommet that, through an
      anatomically contoured and user friendly design has been designed to minimize
      anaesthetic time by facilitating and expediting its placement and/or removal.

PMID- 16441807
TI  - How we do it: septoplasties under local anaesthetic are suitable for short stay
      surgery; the clinical outcomes.
AB  - . Septoplasties can be performed under local anaesthesia. However, careful
      prevention and treatment of pain during the operation is essential. .
      Septoplasties are suitable operations for short-stay surgery. .Two-years post
      operative, septoplasty relieved the symptoms well or excellently in 55% and
      moderately in 27% of the cases. . Specialists prescribe more prophylactic
      antibiotics than residents (47%versus 29%P = 0.02). .Post-operative antibiotics
      do not appear to prevent the development of post-operative infections.

PMID- 16441808
TI  - How we do it: laser reduction of peri-tubal adenoids in selected patients with
      otitis media with effusion.
AB  - . The literature supports the benefit of adenoidectomy in patients with otitis
      media with effusion (OME). . It is difficult to clear adenoid tissue from around
      the Eustachian tubes using curettes and this conventional method of adenoidectomy
      is contra-indicated in patients with cleft palates. . Laser reduction of peri
      Eustachian adenoid tissue without myringotomies or grommet insertion was
      performed in three patients with OME. Two patients had previous adenoidectomies
      performed with curettes and one patient had a cleft palate. . In all three
      patients, the OME resolved and all had closure of the air-bone gap that was
      maintained during long-term follow-up (14 months-4 years). . This technique
      resolved OME without the need for myringotomies or grommet insertion and should
      be considered particularly in patients who have peri-tubal recurrence of
      adenoidal tissue following conventional adenoidectomy or in patients with cleft
      palate where there is concern with regards to palatal incompetence.

PMID- 16441809
TI  - The future of British surgery.

PMID- 16441810
TI  - Blood clots should be evacuated before nasal packing: the problem of the Yankauer
      sucker.

PMID- 16441811
TI  - Variations in the application procedures for the specialist registrar posts in
      otolaryngology.

PMID- 16441812
TI  - Improving communication for the post-operative laryngectomee.

PMID- 16441813
TI  - The Birmingham trainer: a simulator for ligating the lower tonsillar pole.

PMID- 16441815
TI  - Nasal surgery and Eustachian tube function: effects on middle ear ventilation.

PMID- 16441816
TI  - Meta-analysis of the timing of haemorrhage after tonsillectomy.

PMID- 16441817
TI  - Pre-operative localization of parathyroid adenomas: ultrasonography, sestamibi
      scintigraphy or both, continuing the debate.

PMID- 16441818
TI  - Predictors of speech and swallowing function following primary surgery for oral
      and oropharyngeal cancer.

PMID- 16441819
TI  - Quality of life assessment in laryngectomized individuals.

PMID- 16441821
TI  - Mechanisms of dyslipidemia of chronic renal failure.
AB  - Chronic renal failure is associated with profound dysregulation of lipid
      metabolism and marked abnormalities of plasma lipid profile. This review is
      intended to provide an overview of the molecular basis of lipid disorders in
      chronic renal failure and explore their potential impact on cardiovascular
      disease and energy metabolism.

PMID- 16441822
TI  - Visual blurring and metabolic acidosis after ingestion of bootlegged alcohol.
AB  - Extracorporeal treatments have an important role in the management of several
      types of poisonings and drug overdosage. Methanol poisoning is a major problem in
      large parts of the developing world, especially among the economically depressed,
      and is responsible for innumerable deaths annually. Poisoning occurs when
      methanol, a contaminant of bootlegged alcohol, is consumed unknowingly. Toxicity
      is related to formaldehyde and formic acid formed as a result of methanol
      metabolism, and presents as metabolic acidosis, visual impairment, neurological
      manifestations, and shock. Initial symptoms are nonspecific and masked by the
      inebriating effect of ethanol. Appropriate management requires immediate
      administration of ethanol, which competitively inhibits methanol metabolism and
      prevents the generation of toxic formic acid and hemodialysis to achieve
      expeditious clearance of methanol and formic acid. Fomepizole, a safer metabolic
      inhibitor, has largely replaced ethanol in the western world. Delay in seeking
      medical attention contributes to mortality and morbidity. We report on a patient
      who presented to us 8 hr after consumption of countrymade alcohol with symptoms
      of methanol poisoning. Prompt administration of ethanol and institution of
      hemodialysis resulted in complete reversal of all manifestations.

PMID- 16441823
TI  - Composition and clinical use of hemodialysates.
AB  - A thorough knowledge and understanding of the principles underlying the
      preparation and the clinical application of hemodialysates can help us provide
      exemplary patient care to individuals having end-stage renal disease. It is
      prudent to be conversant with the following: (a) how each ingredient in a
      dialysate works, (b) the clinical circumstances under which the concentration of
      an ingredient can be altered, and (c) the special situations in which
      unconventional ingredients can be introduced into a dialysate. The potential to
      enrich dialysates with appropriate ingredients (such as iron compounds) is
      limited only by the boundaries of our imagination.

PMID- 16441824
TI  - Looking at calcimimetics impact on hypercalcemia of immobilization: hypotheses
      and a case study.
AB  - For the treatment of secondary hyperparathyroidism (HPTH-II) in dialysis patients
      and hypercalcemia in patients with parathyroid carcinoma. Calcimimetics are a new
      class of drugs approved in the European Community and the United States by the
      Food and Drug Administration that were designed to suppress parathyroid hormone
      (PTH) levels with a simultaneous reduction in serum calcium and phosphorus
      levels, and calcium phosphorus product (Ca x P). Hypocalcemia is a frequent
      finding during the correction phase of the HPTH-II with calcimimetics. By
      contrast, the appearance of a hypercalcemia has yet to be described. In this
      paper, we report a case of severe hypercalcemia of immobilization in a 40-year
      old hemodialyzed woman treated by cinacalcet HCl for a severe HPTH-II (PTH>1,000
      pg/mL). A kidney transplantation recipient 1983 to 1995, she was diagnosed with
      Charcot-Marie Tooth disease in 1991. She had multiple orthopedic interventions
      for kidney-related osteoarticular problems probably favored by the kidney graft
      and the immunosuppressive treatment. While she was receiving the maximum dose of
      180 mg/day of cinacalcet HCl and PTH at 443 pg/mL, she needed to be hospitalized
      for a right hip prothesis. Two weeks after the intervention she developed a
      symptomatic hypercalcemia of 3.57 mmol/L which was resistant to several measures
      including lowering the calcium concentration in the dialysate, withdrawing all
      vitamin D and calcium supplementation and the administration of calcitonin. Her
      serum calcium level was finally stabilized in the 2.37-2.95 mmol/L by
      administration of a single intravenous dose of pamidronate. This observation
      illustrates that the pharmacological activation of the parathyroid CaR and other
      putative CaR on bone cells by calcimimetics did not protect against the
      occurrence of hypercalcemia of immobilization favored by a severe HPTH-II in a
      hemodialysis patient.

PMID- 16441825
TI  - Screening for depression in chronic hemodialysis patients: comparison of the Beck
      Depression Inventory, primary nurse, and nephrology team.
AB  - Depression in patients with end-state renal disease (ESRD) is both underdiagnosed
      and treated, which may contribute to an increase in morbidity and mortality.
      Efforts aimed at screening, diagnosing, and treating depression could potentially
      modify outcomes in this population. The purpose of this study was to compare the
      prevalence of depression, as measured by the Beck Depression Inventory (BDI-II),
      the primary nurse, and nephrology team, among a cohort of patients receiving
      chronic hemodialysis (HD). A secondary objective was to identify patient
      variables associated with depression. Patients were screened for depression at
      the same time point, using the BDI-II, the primary nurse and the nephrology team.
      Depression was defined as a BDI-II score > or =14. Agreement between the BDI-II
      score, nurse, and nephrology team assessment of depression was compared using a
      kappa score and receiver-operating characteristic (ROC) curves were generated.
      One hundred and twenty-four of an eligible 154 patients completed the study.
      Depression as measured by a BDI-II> or =14, the nurse and the team was diagnosed
      in 38.7%, 41.9%, and 24.2% of patients, respectively. With the BDI-II as the gold
      standard, the nurses' diagnosis of depression had an agreement of 74.6% vs. only
      24.2% agreement with the nephrology team. A previous history of malignancy was
      the only variable associated with the diagnosis of depression. Depression is
      common among patients on HD, supporting the need for a routine depression
      screening program. The primary dialysis nurse is in a key position to identify
      patients with depression and should be considered as an integral part of the
      nephrology team.

PMID- 16441826
TI  - Protecting the endothelium: a new focus for management of chronic kidney disease.
AB  - It is being increasingly recognized that cardiovascular disease (CVD) and its
      complications are the most important cause of morbidity and mortality in patients
      with chronic kidney disease (CKD) and dialysis patients. If outcomes for these
      patients are to be improved, therapeutic strategies at all stages of CKD will
      have to target the etiologies and mechanisms that lead to CVD. In this review, we
      focus on the central role of endothelial dysfunction as the critical precursor of
      CVD. We argue that a better understanding of endothelial dysfunction by
      nephrologists and dialysis physicians is necessary if there is to be success in
      limiting the CVD epidemic that kills and maims our patients. The extensive
      studies to explain the high prevalence of vascular disease in patients with CKD
      have shown the close relationship among endothelial dysfunction, inflammation,
      and atherosclerosis. The pathogenesis starts with endothelial cell injury from
      any of many possible causes, and strategies to reduce the burden of CVD in uremic
      and dialysis patients must be directed at restoring normal endothelial function
      or, at the least, preventing aggravation of endothelial damage. At the center of
      the exploration of endothelial dysfunction and atherosclerosis are oxidative
      stress and inflammation. Of these, which is the chicken and which is the egg is
      unknown, but in the setting of uremia, endothelial injury because of free
      radical, oxidative stress is likely to precede inflammation. The issues raised
      here are highly complex and most renal practitioners may not have been adequately
      exposed to the background research underlying current thinking of the
      pathogenesis of vascular disease. Clearly, progress in management of CVD in
      patients with CKD will require collaboration with experts in the research and
      treatment of vascular disease. Nephrologists seeking optimum outcomes for
      patients with CKD will need to become "endotheliologists" or, at the least,
      subscribe to a mission "to protect the endothelium."

PMID- 16441827
TI  - Primary high-dose intradermal hepatitis B vaccination in hemodialysis: cost
      effectiveness evaluation at 2 years.
AB  - Reinforced hepatitis B (HB) vaccination schedules have been tested in
      nonresponsive hemodialysis (HD) patients. Primary high-dose intradermal (ID)
      vaccination in HD has been proposed in one study with higher seroconversion rate,
      but no cost analysis was made. The aim of this prospective study was to confirm
      this previous report and focus on a cost-effectiveness evaluation of the thorough
      vaccination with a maintenance program. Thirty-five chronic incident HD patients
      received primary ID HB vaccination with a reinforced schedule (20 microg Engerix
      B every 2 weeks). Revaccination with a monthly single ID dose of 20 microg was
      performed whenever anti-HBs titer fell under 20 IU/L and continued until a titer
      of 20 U/L was reached. Outcome measures were cumulative seroconversion rates,
      mean levels of anti-HBs, maintenance booster doses, rate of seroprotection at the
      end of the 2-year follow-up and subsequent costs. The present study was
      associated with an earlier peak of anti-HBs titer (3.9+/-1.7 months) and a higher
      cumulative seroconversion rate (96.9%) after 1 year. Moreover, a low-booster shot
      (17.4 microg) of ID Engerix-B/year/patient confers a 100% seroprotection for all
      responders for a second-year period. The mean cost of our schedule is 127.7
      euro/patient for a 2-year period, revaccination included. This current study
      demonstrates that primary reinforced ID HB vaccination with a maintenance program
      for a 2-year period warrants the best cost-effectiveness ratio with rapid and
      sustained seroprotection in almost all HD patients.

PMID- 16441828
TI  - Mortality differences among organisms causing septicemia in hemodialysis
      patients.
AB  - Septicemia is a serious problem in hemodialysis patients because it can lead to
      life-threatening complications and a persistently elevated risk of death. Most
      analyses have not examined whether there are differences in mortality risk among
      the organisms that cause these episodes of septicemia. This study was a
      retrospective cohort analysis of first septicemia hospitalizations during the
      first year of hemodialysis. Time to death (both in-hospital and within 12 weeks
      post-discharge) was compared among the different septicemia-causing organisms
      based on discharge diagnoses in Medicare billing data from 1996 to 2001. The
      effect of various complications on mortality risk was also evaluated. There were
      22,130 septicemia hospitalizations identified. The most common organism
      identified was Staphylococcus aureus (27%), with no other organism having an
      incidence >10%. The overall unadjusted death rate from admission through 12 weeks
      of follow-up was 34%. During the first hospitalization, the death rate was 14%,
      and during the 12-week period after the hospitalization it was 20%. In adjusted
      analyses, S. aureus was associated with a 20% higher risk of death both during
      the in-hospital period and the 12-week post-discharge period, when compared with
      all other specified organisms. Hospitalizations complicated by meningitis,
      stroke, or endocarditis were also associated with increased risk of mortality,
      independent of the organism causing septicemia. Septicemia hospitalizations are
      associated with a high mortality rate--both during the initial hospitalization
      and after discharge. Meningitis, stroke, and endocarditis represent particularly
      serious complications. Overall, septicemia hospitalizations (especially for S.
      aureus) are serious events, and patients would benefit from better treatment and
      prevention.

PMID- 16441829
TI  - Comparison of side hole versus non side hole high flow hemodialysis catheters.
AB  - Current literature suggests that side holes may be detrimental to dialysis
      catheter performance. Today, these catheters are primarily available with side
      holes. The purpose of this study was to compare flow rates, infection rate, and
      survival of side hole vs. non side hole hemodialysis catheters. Over a 16-month
      period patients were arbitrarily assigned to either a 14.5 F MAHURKAR MAXID
      cuffed dual lumen tunneled catheter with side holes or a 14.5 F MAHURKAR MAXID
      cuffed dual lumen tunneled catheter without side holes ("non side hole
      catheters"). We performed a retrospective analysis of catheter flow rates,
      patency, catheter survival, and catheter-related infections. Information was
      gathered for the life of the catheter or up to 28 weeks. A total of 54 patients
      were enrolled in the study. Thirty-seven of 54 (68%) patients received a catheter
      with side holes for a total of 3,930 catheter days and 17/54 (32%) received a
      similar catheter without side holes for a total of 2,188 catheter days. Catheter
      infection necessitating removal of the catheter occurred in 10/37 catheters with
      side holes and 1/17 without side holes. Infection rates per 1,000 catheter days
      were 2.545 with side holes and 0.254 without side holes (p<0.001). Slightly
      improved catheter survival (p<0.05) was recorded with the non side hole
      catheters. No insertion complication (e.g., air embolization, bleeding, or
      kinking) occurred with either catheter. One catheter without side holes had to be
      repositioned 5 days after insertion because of poor flows. No significant
      difference was recorded in mean blood flow rates between the catheters. Results
      indicate reduced catheter infection rate in hemodialysis patients with the use of
      non side hole dual lumen tunneled cuffed catheters.

PMID- 16441830
TI  - Extravascular lung water index: a new method to determine dry weight in chronic
      hemodialysis patients.
AB  - To assess the dry weight of chronic hemodialysis (HD) patients, the extravascular
      lung water index (ELWI) as a volume parameter was investigated to identify fluid
      overload. Forty-two patients (30 males, 12 females) with a mean age of 55.7+/
      13.0 years who were clinically not overhydrated were connected to the PiCCO
      system before starting HD treatment. We determined ELWI (normal range 3-7 mL/kg)
      and the following parameters: global end-diastolic volume index (GEDI, normal
      range 680-800 mL/m(2)) and intrathoracic blood volume index (ITBI, normal range
      850-1000 mL/m(2)) before and after HD to assess the volume status. Brain
      natriuretic peptide (BNP), aldosterone, and renin as vasoactive hormones were
      measured at the beginning and at the end of HD treatment as well. In 28 of the 42
      patients (67%), elevated values of ELWI were found, indicating interstitial
      volume overload. There were significant correlations between ELWI and cardiac
      function index (p=0.003; Pearson's coefficient -0.451), global ejection fraction
      (p=0.012; Pearson's coefficient -0.389), ITBI (p=0.004; Pearson's coefficient
      0.437), and GEDI (p=0.004; Pearson's coefficient 0.437). No significant relations
      among ELWI and mean arterial pressure (MAP), BNP, aldosterone, and renin were
      found. In conclusion, the use of ELWI is safe in chronic HD patients and
      identifies fluid-overloaded patients, who show no obvious signs of hypervolemia.
      The determination of ELWI is an excellent method to quantify the exact volume in
      chronic HD patients.

PMID- 16441831
TI  - Clinical use of high-efficiency hemodialysis treatments: long-term assessment.
AB  - Significant technological changes in blood flow rate, dialyzer membrane
      permeability, bicarbonate dialysate, and ultrafiltration-controlled delivery
      systems permitted the implementation of 3 modifications to conventional
      hemodialysis as follows: high-efficiency hemodialysis (HEHD), high-flux
      hemodialysis (HFHD), and double-high-flux hemodiafiltration (HDF). The impact of
      these techniques on the quantity of the treatment administered and treatment time
      were assessed. One hundred and eighty-three patients were enrolled over 6 years.
      Monthly Kt/Vurea and dialysis treatment time were compared among the treatment
      techniques. In vivo extracorporeal clearances were measured for the dialyzers
      used. In vivo kinetically derived effective dialyzer clearances were calculated
      from Kt/V. Patient survival and standardized mortality ratio (SMR) were
      determined for each treatment modality. Treatment time averaged 192+/-28, 176+/
      29, and 159+/-32 min, Kt/Vurea averaged 1.33+/-.34, 1.29+/-.30, 1.41+/-.32, and
      in vivo delivered urea clearance averaged 222+/-51, 272+/-34, and 333+/-43 mL/min
      for HEHD, HFHD, and HDF, respectively. These results were achieved even in
      patients with body weights in excess of 80 kgs. Net ultrafiltration rate during
      the treatment reached 20-30 mL/min, without clinical untoward effects. Blood flow
      rate ranged between 450-650 mL/min in all patients. Kaplan-Meier Survival
      analysis yielded a significant difference when high-efficiency treatments were
      compared with USRDS outcomes. Standardized mortality ratio analysis showed
      significance for only HDF vs. USRDS. High-efficiency treatments can provide the
      same quantity of treatment in a shorter period of time without affecting
      mortality. The increased spectrum of solutes removal provided by HFHD and HDF may
      be a further advantage of these treatments.

PMID- 16441832
TI  - Survival to discharge among patients treated with continuous renal replacement
      therapy.
AB  - Continuous renal replacement therapy (CRRT) is widely used in critically ill
      patients with acute renal failure (ARF). The survival of patients who require
      CRRT and the factors predicting their outcomes are not well defined. We sought to
      identify clinical features to predict survival in patients treated with CRRT. We
      reviewed the charts of all patients who received CRRT at the Toronto General
      Hospital during the year 2002. Our cohort (n=85) represented 97% of patients
      treated with this modality in 3 critical care units. We identified demographic
      variables, underlying diagnoses, transplantation status, location (medical
      surgical, coronary, or cardiovascular surgery intensive care units), CRRT
      duration, baseline estimated glomerular filtration rate (eGFR), and presence of
      oliguria (<400 mL/day) on the day of CRRT initiation. The principal outcome was
      survival to hospital discharge. Among those alive at discharge, we assessed
      whether there was an ongoing need for renal replacement therapy. Greater than one
      third (38%, 32/85) of patients survived to hospital discharge. Three (9%)
      survivors remained dialysis-dependent at the time of discharge. Survivors were
      younger than nonsurvivors (mean age 56 vs. 60 years), were on CRRT for a shorter
      duration (7 vs. 13 days), and had a higher baseline eGFR (74 vs. 62 mL/min/m(2)).
      Patient survival varied among different critical care units (medical surgical
      33%, coronary 38%, and cardiovascular surgery 45%). Multivariable logistic
      regression revealed that shorter duration of CRRT, nonoliguria, and baseline eGFR
      >60 mL/min/m(2) were independently associated with survival to hospital discharge
      (p<0.05). Critically ill patients with ARF who require CRRT continue to have high
      in-hospital mortality. A shorter period of CRRT dependence, nonoliguria and
      higher baseline renal function may predict a more favorable prognosis. The
      majority of CRRT patients who survive their critical illness are independent of
      dialysis at the time of hospital discharge.

PMID- 16441833
TI  - HCO3 increment in arterial line can reveal significant vascular access
      recirculation in high-flux hemodialysis: a preliminary report.
AB  - We report a new and simple way that can reveal the presence of vascular access
      recirculation (VAR) in patients undergoing hemodialysis (HD). Acid-base and blood
      gas parameters (pH, pO(2), pCO(2), and HCO(3)) were measured in blood samples
      drawn from an arterial fistula needle before the initiation of HD and from
      arterial and venous lines simultaneously 5 min later, in 31 patients (group A).
      Vascular access recirculation was measured using the glucose infusion test (GIT)
      immediately after the withdrawal of the 5-min samples. The same study was
      repeated in 30 patients in whom HD lines were reversed (group B). A comparison
      with baseline (predialysis) values of an analysis of the arterial line in group A
      at 5 min revealed that pCO(2) increased by 1.14+/-2.5 mmHg and HCO(3) by 0.6+/
      0.6 mM/L (p<0.02 and p<0.00001, respectively). The corresponding pO(2) and pH
      values did not show significant differences. Glucose infusion test at 5 min
      (GITa) was -0.058+/-0.03%. A comparison with baseline (predialysis) values of an
      analysis of the arterial line in group B at 5 min revealed that pCO(2) increased
      by 7.7+/-3.5 mmHg and HCO(3) by 2.9+/-1.0 mM/L (p<0.000001 in each case). The pH
      level was significantly lower in comparison with baseline values (p<0.00001),
      while pO(2) did not show a significant difference. Glucose infusion test at 5 min
      (GITb) was 12.0+/-6.1% (p<0.000001 in comparison with GITa values). Clinically
      significant VAR was defined as HCO(3) increment >1.8 mM/L, based on the receiver
      operating characteristics curve, which showed a threshold value of HCO(3)
      increment >1.8 mmol/L as a predictor of GIT recirculation. Five minutes after the
      initiation of high-flux HD with a 0 ultrafiltration rate, there is a small
      increment in arterial HCO(3) values relative to predialysis values. Clinically
      significant VAR is present when this increment is higher than 1.8 mM/L.

PMID- 16441834
TI  - Characteristics of ototoxicity of aminoglycosides "locked" to prevent
      hemodialysis catheter-related infections.

PMID- 16441837
TI  - Regulatory issues in aging pharmacology.
AB  - Many current drugs increase the average lifespan by preventing fatal diseases or
      by slowing down the progressive degenerative diseases that increase mortality.
      The existing strategies and guidelines for the development and regulatory
      approval of new drugs are designed for such compounds. Rapid advances in
      understanding molecular mechanisms of aging make it possible to envisage future
      drugs that extend the lifespan by regulating aging mechanism outside of disease
      pathways. Strategies for development and regulatory approval of such drugs remain
      to be defined. Since the drug candidates will be given to healthy, elderly
      subjects, safety requirements will be extremely high. Clinical studies of many
      years' duration will be necessary to prove changes in longevity. These time
      intervals may exceed those of patent protection and thus minimize commercial
      incentives. Despite these challenges, two broadly defined pathways are feasible.
      First, it may be possible to obtain public funding for studies with voluntary
      participation of humans consuming existing drugs or natural compounds in the
      'expected to be safe' category. Second, the development of novel drugs may
      proceed on the basis of well-defined biomarkers of aging that can serve as
      surrogate end points in clinical studies. The emerging approaches will prompt the
      regulatory agencies into taking the first steps towards regulatory guidance.

PMID- 16441838
TI  - Exploiting the rodent model for studies on the pharmacology of lifespan
      extension.
AB  - The rodent is a particularly valuable model with which to test therapeutic
      interventions for aging, as rodent physiology is close enough to human physiology
      to give the findings relevance for human aging, and it is small enough to allow
      for use of statistically robust sample sizes. There are many rodent models to
      choose from, with advantages and disadvantages to each. The choice of model
      system, as well as other experimental design decisions such as diet and housing,
      is extremely important for the success of lifespan studies. These issues are
      discussed in this review of the use of the rodent model. The National Institute
      on Aging (NIA) Interventions Testing Program, which has grappled with all of
      these issues, is described.

PMID- 16441839
TI  - Rules for the use of model organisms in anti-aging pharmacology.
AB  - The use of animal models for initially screening anti-aging drugs is a promising
      approach for drug discovery. However, there a number of potential artifacts,
      confounds and errors that can arise in such research programs. The following
      rules are intended to minimize such problems: (1) since aging occupies an
      increasing proportion of human adulthood, data that conflate aging and late life
      should not be extrapolated to human aging; (2) the response to candidate
      medications should show a normal dose-response pattern, although not necessarily
      a linear response; (3) medicated animal models should not be hypometabolic; (4)
      medicated animal models should not show pronounced reductions in fertility; (5)
      medicated animal models should not exhibit general nervous system depression; (6)
      the effect of the medication should not be highly sensitive to the culture
      environment; (7) the effect of the medication should not be highly dependent on
      the genetic ancestry of the stock employed, leaving aside inbreeding, which
      should be avoided because humans are not generally inbred. While these rules do
      not guarantee successful extrapolation of successful drug results from the animal
      model to humans in a clinical setting, the failure to adhere to these rules
      should raise doubts about such extrapolation.

PMID- 16441840
TI  - Endocrine targets for pharmacological intervention in aging in Caenorhabditis
      elegans.
AB  - Studies in the nematode Caenorhabditis elegans have been instrumental in defining
      genetic pathways that are involved in modulating lifespan. Multiple processes
      such as endocrine signaling, nutritional sensing and mitochondrial function play
      a role in determining lifespan in the worm and these mechanisms appear to be
      conserved across species. These discoveries have identified a range of novel
      targets for pharmacological manipulation of lifespan and it is likely that the
      nematode model will now prove useful in the discovery of compounds that slow
      aging. This review will focus on the endocrine targets for intervention in aging
      and the use of C. elegans as a system for high throughput screens of compounds
      for their effects on aging.

PMID- 16441842
TI  - Use of microarray biomarkers to identify longevity therapeutics.
AB  - A number of lines of evidence, including nonhuman primate and human studies,
      suggest that regulatory pathways similar to those invoked by caloric restriction
      (CR) may be involved in determining human longevity. Thus, pharmaceuticals
      capable of mimicking the molecular mechanisms of life- and health-span extension
      by CR (CR mimetics) may have application to human health. CR acts rapidly, even
      in late adulthood, to begin to extend life- and health-span in mice. We have
      linked these effects with rapid changes in the levels of specific gene
      transcripts in the liver and the heart. Our results are consistent with the rapid
      effects of caloric intake on the lifespan and/or biochemistry and physiology of
      Drosophila, rodents, rhesus macaques and humans. To test the hypothesis that
      existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated
      the effectiveness of glucoregulatory drugs and putative cancer chemo
      preventatives in reproducing the hepatic gene-expression profiles produced by
      long-term CR (LTCR). We found that 8 weeks of metformin treatment was superior to
      8 weeks of CR at reproducing the specific changes in transcript levels produced
      by LTCR. Consistent with these results, metformin reduces cancer incidence in
      diabetic humans and ameliorates the onset and severity of metabolic syndrome.
      Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu
      mice by 8% and 13.1% in comparison with control mice. Phenformin, a close
      chemical relative of metformin, extends lifespan and reduces tumor incidence in
      C3H mice. These results indicate that gene-expression biomarkers can be used to
      identify promising candidate CR mimetics.

PMID- 16441841
TI  - Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for
      pharmacological manipulation of lifespan.
AB  - Much excitement has arisen from the observation that decrements in insulin-like
      signaling can dramatically extend lifespan in the nematode, Caenorhabditis
      elegans, and fruitfly, Drosophila melanogaster. In addition, there are
      tantalizing hints that the IGF-I pathway in mice may have similar effects. In
      addition to dramatic effects on lifespan, invertebrate insulin-like signaling
      also promotes changes in stress resistance, metabolism and development. Which, if
      any, of the various phenotypes of insulin pathway mutants are relevant to
      longevity? What are the genes that function in collaboration with insulin to
      prolong lifespan? These questions are at the heart of current research in C.
      elegans longevity. Two main theories exist as to the mechanism behind insulin's
      effects on invertebrate longevity. One theory is that insulin programs metabolic
      parameters that prolong or reduce lifespan. The other theory is that insulin
      determines the cell's ability to endure oxidative stress from respiration,
      thereby determining the rate of aging. However, these mechanisms are not mutually
      exclusive and several studies seem to support a role for both. Here, we review
      recently published reports investigating the mechanisms behind insulin's dramatic
      effect on longevity. We also spotlight several C. elegans genes that are now
      known to interact with insulin signaling to determine lifespan. These insights
      into pathways affecting invertebrate lifespan may provide a basis for developing
      strategies for pharmacological manipulation of human lifespan.

PMID- 16441843
TI  - Nitrones as therapeutics in age-related diseases.
AB  - Age-related diseases deprive individuals of a higher quality of life and
      therefore therapeutics for their treatment provide significant potential. An
      overview of the observations of nitrones as potential therapeutics in several age
      related diseases is presented. Treatment of acute ischemic stroke is one
      condition where a nitrone (NXY-059) is in late phase 3 clinical trials now. Also
      presented is a summary of the most recent work we have accomplished on the
      anticancer activity of the nitrones in a hepatocellular carcinoma. The
      mechanistic basis of action of these compounds in several animal models is not
      yet understood at the molecular levels; however, it does appear clear that their
      anti-inflammatory properties are central to their action, which is based on their
      ability to down-regulate exacerbated signal transduction processes.

PMID- 16441845
TI  - Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn complexes in
      Alzheimer's disease.
AB  - Neocortical beta-amyloid (Abeta) aggregates in Alzheimer's disease (AD) are
      enriched in transition metals that mediate assembly. Clioquinol (CQ) targets
      metal interaction with Abeta and inhibits amyloid pathology in transgenic mice.
      Here, we investigated the binding properties of radioiodinated CQ ([(125)I]CQ) to
      different in vitro and in vivo Alzheimer models. We observed saturable binding of
      [(125)I]CQ to synthetic Abeta precipitated by Zn(2+) (K(d)=0.45 and 1.40 nm for
      Abeta(1-42) and Abeta(1-40), respectively), which was fully displaced by free
      Zn(2+), Cu(2+), the chelator DTPA (diethylene triamine pentaacetic acid) and
      partially by Congo red. Sucrose density gradient of post-mortem AD brain
      indicated that [(125)I]CQ concentrated in a fraction enriched for both Abeta and
      Zn, which was modulated by exogenous addition of Zn(2+) or DTPA. APP transgenic
      (Tg2576) mice injected with [(125)I]CQ exhibited higher brain retention of tracer
      compared to non-Tg mice. Autoradiography of brain sections of these animals
      confirmed selective [(125)I]CQ enrichment in the neocortex. Histologically, both
      thioflavine-S (ThS)-positive and negative structures were labeled by [(125)I]CQ.
      A pilot SPECT study of [(123)I]CQ showed limited uptake of the tracer into the
      brain, which did however, appear to be more rapid in AD patients compared to age
      matched controls. These data support metallated Abeta species as the
      neuropharmacological target of CQ and indicate that this drug class may have
      potential as in vivo imaging agents for Alzheimer neuropathology.

PMID- 16441844
TI  - Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis
      elegans.
AB  - The beneficial effects of polyphenol compounds in fruits and vegetables are
      mainly extrapolated from in vitro studies or short-term dietary supplementation
      studies. Due to cost and duration, relatively little is known about whether
      dietary polyphenols are beneficial in whole animals, particularly with respect to
      aging. To address this question, we examined the effects of blueberry polyphenols
      on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism
      for such a study. We report that a complex mixture of blueberry polyphenols
      increased lifespan and slowed aging-related declines in C. elegans. We also found
      that these benefits did not just reflect antioxidant activity in these compounds.
      For instance, blueberry treatment increased survival during acute heat stress,
      but was not protective against acute oxidative stress. The blueberry extract
      consists of three major fractions that all contain antioxidant activity. However,
      only one fraction, enriched in proanthocyanidin compounds, increased C. elegans
      lifespan and thermotolerance. To further determine how polyphenols prolonged C.
      elegans lifespan, we analyzed the genetic requirements for these effects.
      Prolonged lifespan from this treatment required the presence of a CaMKII pathway
      that mediates osmotic stress resistance, though not other pathways that affect
      stress resistance and longevity. In conclusion, polyphenolic compounds in
      blueberries had robust and reproducible benefits during aging that were separable
      from antioxidant effects.

PMID- 16441846
TI  - SirT1 fails to affect p53-mediated biological functions.
AB  - The SirT1 gene encodes a protein deacetylase that acts on a number of nuclear
      substrates. p53 was identified as a SirT1 substrate whose transcriptional
      activity was reported to be negatively regulated by SirT1-dependent
      deacetylation. We set out to determine whether developmental defects and
      perinatal lethality observed in SirT1-null mice were caused by p53 hyperactivity
      by creating mice deficient for both SirT1 and p53. Animals null for both proteins
      were smaller than normal at birth, had eyelid opening defects and died during the
      late prenatal and early postnatal periods, a phenotype indistinguishable from
      mice deficient for SirT1 alone. Upon re-examination of the role of SirT1 in
      modulating p53 activity, we found that while SirT1 interacts with p53, the SirT1
      protein had little effect on p53-dependent transcription of transfected or
      endogenous genes and did not affect the sensitivity of thymocytes and splenocytes
      to radiation-induced apoptosis. These findings suggest that SirT1 does not affect
      many p53-mediated biological activities despite the fact that acetylated p53 has
      been shown to be a substrate for SirT1.

PMID- 16441847
TI  - Fibroblasts from long-lived Snell dwarf mice are resistant to oxygen-induced in
      vitro growth arrest.
AB  - Snell dwarf mice live longer than controls, and show lower age-adjusted rates of
      lethal neoplastic diseases. Fibroblast cells from adult dwarf mice are resistant
      to the lethal effects of oxidative and nonoxidative stresses, including the
      carcinogen methyl methanesulfonate. We now report that dwarf-derived fibroblasts
      are slow to enter the stage of growth arrest induced by culturing normal cells
      under standard culture conditions at 20% O(2). Dwarf cells cultured at 20% O(2)
      resemble control cells cultured at 3% O(2) not only in their delayed growth
      arrest, but also in their rapid growth rates and resistance to both oxidative and
      nonoxidative forms of cytotoxic stress. Levels of the heat-shock protein HSP-70
      respond to serum withdrawal and stress only in control cells, showing that
      intracellular signals are blunted in dwarf-derived cells. These data suggest a
      model in which stable epigenetic changes induced in skin fibroblasts by the
      hormonal milieu of the Snell dwarf lead to resistance to multiple forms of
      injury, including the oxidative damage that contributes to growth arrest in vitro
      and neoplasia in intact mice.

PMID- 16441848
TI  - What are children's trusts? Early findings from a national survey.
AB  - BACKGROUND: The Children Act 2004 and National Service Framework for Children,
      Young People and Maternity Services require fuller integration of health,
      education and social services for children and young people in England and Wales.
      The UK government supported the establishment of 35 experimental children's trust
      pathfinders (henceforth called children's trusts) in England. METHODS: A
      questionnaire was completed by managers in all 35 children's trusts a year after
      their start. Children's trust documents were examined. Census and performance
      indicators were compared between children's trust areas and the rest of England.
      RESULTS: Children's trust areas had demographic and social characteristics
      typical of England. All children's trusts aimed to improve health, education and
      social services by greater managerial and service integration. All had boards
      representing the three sectors; other agencies' representation varied. Two-thirds
      of children's trusts had moved towards pooling budgets in at least some service
      areas. At this stage in their development, some had prioritized joint procurement
      or provision of services, with formal managerial structures, while others
      favoured an informal strategic planning, co-ordination and information sharing
      approach. The commonest priorities for services development were for disabled
      children (16 children's trusts), followed by early intervention (11) and mental
      health services (8). CONCLUSIONS: The diverse strategies adopted by these 35
      children's trusts during their first year is due to their own characteristics and
      to the way government strategy developed during this period. Whilst some
      prioritized organizational development, joint financing and commissioning, and
      information sharing, others laid more emphasis on mechanisms for bringing front
      line professionals closer together. Their experiences are of value to others
      deciding how best to integrate children's services.

PMID- 16441849
TI  - Key worker services for disabled children: what characteristics of services lead
      to better outcomes for children and families?
AB  - BACKGROUND: Research has shown that families of disabled children who have a key
      worker benefit from this service and recent policy initiatives emphasize the
      importance of such services. However, research is lacking on which
      characteristics of key worker schemes for disabled children are related to better
      outcomes for families. METHODS: A postal questionnaire was completed by 189
      parents with disabled children who were receiving a service in seven key worker
      schemes in England and Wales. Path analysis was used to investigate associations
      between characteristics of the services and outcomes for families (satisfaction
      with the service, impact of key worker on quality of life, parent unmet need,
      child unmet need). RESULTS: The four path models showed that key workers carrying
      out more aspects of the key worker role, appropriate amounts of contact with key
      workers, regular training, supervision and peer support for key workers, and
      having a dedicated service manager and a clear job description for key workers
      were associated with better outcomes for families. Characteristics of services
      had only a small impact on child unmet need, suggesting that other aspects of
      services were affecting child unmet need. CONCLUSIONS: Implications for policy
      and practice are discussed, including the need for regular training, supervision
      and peer support for key workers and negotiated time and resources for them to
      carry out the role. These influence the extent to which key workers carry out all
      aspects of the key worker's role and their amount of contact with families, which
      in turn impact on outcomes.

PMID- 16441850
TI  - Support for family carers of children and young people with developmental
      disabilities and challenging behaviour.
AB  - BACKGROUND: This study gathered information about perceptions of family carers of
      children and young people with developmental disabilities and challenging
      behaviour of the help, support and treatment received from services and
      professionals. METHODS: A total of 66 family carers completed postal
      questionnaires on the nature of, and their satisfaction with, services,
      professional help and advice received in respect of their family member's
      challenging behaviour. RESULTS: Most carers were dissatisfied with support and
      services received. Almost half reported receiving no professional input or none
      that was helpful. Over two-thirds reported receiving respite care but, in a third
      of these, the child had been excluded because of challenging behaviour.
      CONCLUSIONS: Families of children with challenging behaviour often do not receive
      services and supports that they find helpful. Treatments provided are not always
      evidence based. The 'rationing' of services creates a danger of inequality of
      access. We need a more proactive approach to identifying and meeting the need for
      family support.

PMID- 16441851
TI  - Use of the measure of process of care for families (MPOC-56) and service
      providers (MPOC-SP) to evaluate family-centred services in a paediatric
      disability setting.
AB  - BACKGROUND: The value of family-centred principles in paediatric professional
      caregiving services is widely acknowledged. However, the degree to which such
      services adhere to these principles is not well documented. AIM: To examine the
      perceptions of both families and service providers of the extent to which family
      centred services were being implemented by a paediatric disability service
      provider and to pinpoint areas for improvement. METHOD: A sample of 158 families
      receiving services from the Cerebral Palsy Association of Western Australia
      completed the Measure of Processes of Care for families (MPOC-56) and 43
      clinicians (most of them physiotherapists, speech pathologists and occupational
      therapists) completed the Measure of Processes of Care for service providers
      (MPOC-SP). RESULTS: As in previous studies, the families rated 'respectful and
      supportive care' highest and 'providing general information' lowest. Clinicians
      rated 'showing interpersonal sensitivity' highest and 'providing general
      information' lowest. Analysis of individual items revealed that the following
      areas of family-centred services were in need of improvement: provision of
      general written information to families on a range of issues, continuity of care,
      greater involvement of the family in therapy and provision of more detailed
      information about therapy issues and provision of more general support to whole
      families. CONCLUSIONS: The MPOC tools have been found useful in enabling
      disability service providers to identify areas for improvement and move towards
      providing services that are more family centred.

PMID- 16441852
TI  - Authoritative parenting and parental stress in parents of pre-school and older
      children with developmental disabilities.
AB  - BACKGROUND: Rearing a child with a developmental disability is associated with
      increased parental stress. Theories of stress and adjustment and bi-directional
      theories of child development suggest that parenting could influence these
      negative outcomes. METHODS: Relationships between parenting approaches and stress
      in parents of children with developmental disabilities (DD) (N = 53) were
      examined across two age groups, 3-5 years and 9-11 years and compared with a
      contrast group of typically developing children (TD) (N = 60). Measures used were
      the Parenting Stress Index-Short Form and Rickel and Biasatti's modification of
      Block's Child Rearing Practices Report, classified into Baumrind's parenting
      styles using Reitman and Gross's method. RESULTS: Parents in the older DD group
      used Authoritative parenting less than parents in the younger DD group, while the
      opposite developmental pattern was seen in the TD group. Multivariate analysis of
      variance showed a significant group x parenting style interaction for Parental
      Distress, Parent-Child Dysfunctional Interaction and Difficult Child. Stress
      measures were higher for the DD group and seemed to be associated with
      Authoritative parenting approaches, an effect that was not observed in the TD
      group. CONCLUSIONS: Findings suggest that the well-established effect of group on
      stress may be moderated by parenting style. Authoritative parenting may be highly
      stressful for parents of children with DD to implement, resulting in a decrease
      in its use across the two age groups.

PMID- 16441853
TI  - Discussion groups with parents of children with cerebral palsy in Europe designed
      to assist development of a relevant measure of environment.
AB  - BACKGROUND: An instrument to measure environmental factors relevant to physically
      impaired children is being developed in a European context. Preliminary work in
      England had identified some potentially important themes. Further inquiry was
      needed to identify issues important in other European countries. OBJECTIVE: To
      inform the content of a questionnaire relevant to the environment of children
      with cerebral palsy (CP) living in Europe. DESIGN: A qualitative study using
      discussion groups. PARTICIPANTS: Parents of 28 children with CP from five
      countries; Denmark, France, Italy, Ireland and Sweden. One discussion group was
      held in each country with an average of seven parents per group. RESULTS: The
      four themes identified in the preliminary work done in England were strongly
      confirmed across Europe - namely: Mobility, Transport, Support by and to parents,
      and Attitudes of individuals and institutions towards children. Two new themes
      identified in the discussion groups were Bureaucracy and Access to information
      about rights and entitlements. CONCLUSIONS: The environmental factors that cause
      concern to parents of children with CP are similar across Europe. A prototype
      environmental questionnaire has been developed based on these findings. The
      environmental questionnaire is in use in a study in nine European centres.

PMID- 16441854
TI  - Attention deficit hyperactivity disorder: a review of the essential facts.
AB  - Abstract Attention deficit hyperactivity disorder (ADHD) is a complex disorder,
      where both genetic and environmental influences make a substantial contribution
      to the risk for the disorder. One of the challenges facing clinicians is to
      simplify for parents the multifaceted reasons why their child may have developed
      ADHD, explain the associated symptoms, and encourage parents to participate in
      intervention. Increasing parents understanding about ADHD should make them better
      informed about the disorder, more likely to consent to intervention, and increase
      adherence to both psychosocial and pharmacological treatment. The aim of this
      review is to provide clinicians with a brief synopsis of our current
      understanding about the aetiology of ADHD, co-morbidity and associated problems,
      developmental course and intervention options.

PMID- 16441855
TI  - The marriage-related risk factors during maternal pregnancy in children with
      attention-deficit hyperactivity disorder.
AB  - BACKGROUND: The purpose of this research was to investigate the relationship
      between marriage-related risk factors during maternal pregnancy and subsequent
      development of attention-deficit hyperactivity disorder (ADHD). METHODS: The
      research design was a retrospective case-control study. The case group included
      60 patients that fulfilled the ADHD criteria of Fourth Edition of the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-IV). The controls were normal
      children randomly selected and matched for their sex and age. Their biological
      mothers completed a questionnaire about marital adaptation, marital satisfaction
      and the incidence of stressful life events during pregnancy. RESULTS: The results
      showed that the incidence of positive life events, marital adaptation and marital
      satisfaction during maternal pregnancy was significantly lower in the case group,
      and conditional logistic regression analysis showed that marital adaptation
      during pregnancy and pregnancy before marriage were important risk factors for
      ADHD. CONCLUSION: Negative emotion during maternal pregnancy may be an important
      risk factor for ADHD.

PMID- 16441856
TI  - Characteristics and profile of boys and girls with emotional and behavioural
      disorders in Flanders mental health institutes: a quantitative study.
AB  - BACKGROUND: In this article, we search for gender differences and outline a
      detailed gender profile for children and youngsters with emotional and
      behavioural disorders who are placed in Flemish residential care institutes.
      METHODS: Data were collected of all placements (517 children) in six residential
      and semi-residential mental health care centres for children and youngsters with
      emotional and behavioural disorders in East Flanders, Belgium. File data (gender,
      age, retention, current treatment, type of referral, education, intelligence,
      Diagnostic and Statistical Manual IV-diagnoses and medication use) were gathered.
      The Child Behaviour Check List (CBCL) was implemented and completed for each
      child. On the basis of the CBCL, a behaviour profile was developed by means of
      correlation tables (Pearson correlation coefficient) and cross tabulations.
      Finally, the profile was compared with the file data of the boys and the girls.
      RESULTS: Significant gender differences were found for type of referral,
      intelligence and diagnoses. The same profile was developed for both genders
      separately, based on variables Externalizing and Social Problems. The file data
      associated with the profile groups differ for boys and girls. CONCLUSIONS: The
      results of our study show the complexity and diversity of the needs of boys and
      girls with disruptive behaviour in Flemish residential care institutes. Flemish
      government has to be aware of the fact that the current referral system selects
      the children with outspoken externalizing and problematic behaviour towards
      special health care and special schools. They are relegated because the
      mainstream system is not equipped well enough to cope with their disruptive,
      aggressive behaviour. Even if governments are in favour of inclusive education,
      it seems that in practice a rest group is created, in which girls are selected
      through the same mechanisms as boys, in this case for the same reasons of
      negative externalizing behaviour and social problems. For this it seems
      appropriate that school and (semi)-residential institutes apply a specific and
      adapted methodology.

PMID- 16441857
TI  - Prescribing practices of psychiatrists and primary care physicians caring for
      children with mental illness.
AB  - OBJECTIVE: Although several studies have found that the most effective treatment
      for both youths and adults diagnosed with mood disorders is the combination of
      psychotherapy and medications, psychiatrists have been increasingly providing
      psychotropic medications without psychotherapy to these populations. At the same
      time, primary care physicians (PCPs) have become increasingly involved in
      prescribing psychotropic medications. This study compared the prescribing
      patterns of PCPs and psychiatrists caring for children with mental illness.
      METHODS: Data were extracted from the MarketScan database, which compiles claims
      from private health insurance plans nationwide. Of 40,639 children who received
      mental health services during calendar year 2000 (6.33% of all covered children),
      we identified 5485 who initiated a new episode of treatment. Multiple regression
      was use to adjust for differences in patient characteristics. RESULTS: While PCPs
      were more likely to see young children and psychiatrists saw children with more
      numerous mental illnesses, there were no significant differences between PCPs and
      psychiatrists in either the proportion of patients who received psychotropic
      medication, the frequency of clinical contacts, or the dosages or types of
      medications prescribed. Patients seen in more actively managed Point of Service
      plans were more likely to receive medication than those seen in preferred
      provider or indemnity plans. CONCLUSIONS: This study found no significant
      differences between psychiatrists and PCPs in psychotropic prescribing practices.
      In view of the limited availability of child psychiatrists and the decreased
      availability of psychotherapy in combination with medications, collaborative care
      models in which non-physician mental health specialists and PCPs work together
      may increase the availability of effective mental health services for youths.

PMID- 16441858
TI  - A simple, and potentially low-cost method for measuring the prevalence of
      childhood obesity.
AB  - BACKGROUND: Recent official publications have highlighted obesity as one of the
      biggest threats to public health and the prevalence of obesity in children is
      widely believed to be rising rapidly. However, there are no data on the
      prevalence of childhood obesity at a local level. We have developed a simple low
      cost method of gaining such data by working with local schools. METHOD: We
      designed our method on the observation that numeracy and data handling skills are
      often taught in schools by getting children to measure their height and weight.
      We recruited seven schools and offered them a numeracy lesson plan suitable for
      year 5 (aged 9-10) children together with healthcare staff to attend the lesson.
      As part of the lesson, each child's height and weight was measured and recorded
      anonymously. Parental consent was obtained on an 'opt out' basis. The method was
      evaluated by questionnaire. RESULTS: We gained data on body mass index for 252
      children. In total, 20% of the children were overweight, and 7% obese. The brief
      questionnaire survey indicated that both teachers and school nurses were happy
      with the method and would repeat it. Weighing was carried out sensitively.
      CONCLUSION: Our findings were in line with national studies of the prevalence of
      childhood obesity. The method was simple, low-cost and acceptable to schools and
      school nurses. There seems no reason why this project cannot be used more widely
      across the Primary Care Trust (PCT) and beyond. We now propose to roll out the
      method across all primary schools in Birmingham.

PMID- 16441859
TI  - Measuring the prevalence of childhood obesity: a minimalist approach may be the
      best option.

PMID- 16441861
TI  - Water treatment and monitor disinfection.
AB  - Water treatment system and dialysis monitors are susceptible to microbial
      contaminations and periodical disinfection procedures are mandatory to obtain
      results requested from international standards and guidelines. Several chemical
      germicides or some physical treatments are on the market validated by device
      manufacturer according to medical device directives. With time, interfering
      substances from dialysis device or water are able to modify disinfection
      efficiency. Simulating-use testing is not a common procedure to validate
      disinfectants and recent data document as biofilm represents the most important
      cause of disinfection inefficacy. Some international standards include tests in
      the presence of various interfering substances but their use is not widespread.
      When using a disinfectant, residue toxicity, material compatibility and potential
      risks for the staff also have to be considered. A quality assurance program has
      to be implemented to obtain adequate performances and to improve results on
      patients.

PMID- 16441862
TI  - Challenges and future of renal replacement therapy.
AB  - Renal community increasingly recognizes the challenges of very high mortality,
      morbidity and low quality of life among dialysis patients. Current hemodialysis
      (HD) schedule provides less than 10% of the clearance power of the natural
      kidneys and therefore current standard HD treatment is still a long way from
      providing adequate renal replacement. In the future it would be expected to
      improve dialysis control with the development of new technology: membranes,
      dialysate buffer, electrolyte concentration, system interface, arteriovenous
      access monitoring. Online technology must be adapted to routine HD for new
      prescription monitoring such as creatinine online sensing technology, sodium
      specific electrode or hydrogen ion concentration. Online convective therapies
      offer the opportunity for a more biological renal replacement therapy increasing
      convective transport in order to "reproduce" glomerular function and improving
      small and middle molecular clearance in an economically feasible and safe way.
      The paradigm of thrice-weekly dialysis is faced with diminishing returns, with
      the possible exception of long dialysis sessions. More frequent (daily) dialysis
      represents a very promising tool for improving dialysis outcomes and quality of
      life. Future technologies for renal replacement include bioartificial kidneys
      based in continuous hemofiltration and bioartificial tubules. Although Phase I/II
      clinical trial on 10 patients with acute renal failure has been reported the
      procedure requires further evaluation. Organogenesis, therapeutic cloning, or
      cloning and organogenesis combined might in the future produce a functional and
      histocompatible kidney. The continuous increase in incidence and prevalence of
      renal-replacement therapy is a world-wide phenomenon, although the rates in
      Europe are still much lower than in the U.S. The increase in rates applies
      especially to older patients, patients with diabetes mellitus and renal vascular
      disease and the consequences of this important comorbidity are very important in
      terms of mortality.

PMID- 16441863
TI  - Removal of uremic plasma factors using different dialysis modalities.

PMID- 16441864
TI  - Microinflammation in hemodialysis is related to a preactivated subset of
      monocytes.
AB  - Increased percentage of monocytes with low CD14 expression and that co-express
      CD16 (CD14+/CD16+) have been reported in hemodialysis (HD) patients. We sought to
      determine whether CD14+/CD16+ monocytes in HD therapy are sensibilized cells to a
      proinflammatory activity. Cells from 32 HD patients, and from 9 Systemic Lupus
      Erythematosus (SLE), 9 individuals with human immunodeficiency virus (HIV)-1- and
      15 healthy controls were studied. Cells were analyzed by means of flow cytometry
      for CD14/CD16 expression and immune function (cytokine, chemokines, and
      sialoadhesin expression), and phagocytosis. Increased percentage of CD14+/CD16+
      monocytes was observed in HD patients. Compared with CD14++ monocytes, the
      CD14+/CD16+ monocytes exhibited increased expression of proinflammatory cytokines
      and markers of differentiated cells. In addition, these monocytes showed an
      increased phagocytic activity. Similarly, CD14+/CD16+ monocytes from SLE and HIV
      patients showed increased inflammatory activity as compared with CD14++ cells.
      These results support that CD14+/CD16+ monocytes from HD patients evidence
      characteristics of primed prestimulated proinflammatory cells, similar to data
      observed in SLE and HIV.

PMID- 16441865
TI  - Online hemodiafiltration: 4 years of clinical experience.
AB  - Online hemodiafiltration (online HDF) is a new hemodialysis technique combining
      convection and diffusion and thus also enabling the purification of large
      molecules. As yet, only a small number of clinical experiences have been
      published about the effectiveness and safety of online HDF. We present a
      prospective and observational study conducted on 31 patients treated with online
      HDF in our center in the last 4 years. The purpose of the study is to compare the
      evolution of the following aspects before and after starting online HDF: dose of
      dialysis, purification of medium-sized/large molecules, inflammation, nutrition,
      Ca-P metabolism, anemia, and intradialytic complications. Online HDF increased
      Kt/V to 31.0% (p > 0.001) and reduced postdialysis beta(2)-M to 66.4% (p >
      0.001). The rest of the parameters analyzed did not vary significantly. During
      online HDF, episodes of symptomatic hypotension fell by 45% in relation to
      conventional hemodialysis, and no relevant complication occurred. Online HDF is
      very useful in patients in whom we need to increase replacement therapy, such as
      patients with a large body surface, those in whom we suspect a residual syndrome
      or those who have been receiving dialysis for a long time and for whom we wish to
      prevent amyloidosis. Online HDF is safe and better tolerated than conventional
      hemodialysis.

PMID- 16441866
TI  - The relevance of convection in clinical practice: a critical review of the
      literature.
AB  - Convective treatments (high-flux hemodialysis (HD), hemodiafiltration and
      hemofiltration) are characterized by enhanced removal of middle and large
      molecular weight solutes compared with conventional low-flux HD. As these
      molecules are claimed to play an important role in the genesis of many
      complications of chronic HD, the availability of these techniques represented an
      intriguing innovation and a possible means to improve the still poor prognosis of
      HD patients. Here we will critically review the most important published studies
      comparing convective treatments with low-flux HD on chronic morbidity,
      preservation of residual renal function, and long-term survival.

PMID- 16441867
TI  - Bases of cardiovascular and hematological effects.

PMID- 16441869
TI  - Hemodialysis membranes for high-volume hemodialytic therapies: the application of
      nanotechnology.

PMID- 16441868
TI  - How to implement online HDF in a dialysis unit.

PMID- 16441870
TI  - Overview of clinical studies in hemodiafiltration: what do we need now ?
AB  - Despite several technical advances in dialysis treatment modalities and a better
      patient care management including correction of anemia, suppression of secondary
      hyperparathyroidism, lipid and oxidative stress profiles improvement, the
      morbidity and the mortality of dialysis patients still remain still elevated.
      Recent prospective interventional trials in hemodialysis (HEMO study and 4D
      study) were not very conclusive in showing any significant improvement in
      dialysis patient outcomes. High-efficiency convective therapies, such as online
      hemodiafiltration (HDF), are claimed to be superior to conventional diffusive
      hemodialysis (HD) in improving the dialysis efficacy and in reducing
      intradialytic morbidity and all-cause and cardiovascular mortality in dialysis
      patients. The aim of this report was, first, to review the evidence-based facts
      tending to prove the superiority of HDF vs. HD in terms of efficacy and
      tolerance, and, second, to analyze the needs to prove the clinical superiority of
      HDF in terms of reducing morbidity and all-cause mortality of dialysis patients.
      A systematic review of studies comparing HDF and HD has been performed in the
      microbiological safety of online production, the solute removal capacity of small
      and medium-size uremic toxins, and its implication in the reduction of the
      bioactive dialysis system vs. patient interaction. Major planned randomized
      international studies comparing HDF and HD in terms of morbidity and mortality
      have been reviewed. To conclude, it is thought that these long-term prospective
      randomized trials will clarify on a scientific evidence-based level the putative
      beneficial role of high-efficiency HDF modalities on dialysis patient outcomes.

PMID- 16441871
TI  - Cardiovascular dialysis instability and convective therapies.
AB  - Acute hypotension is a frequent hemodialysis complication. Intratreatment
      vascular instability is a multifactorial process in which procedure-related and
      patient-related factors may influence the decrease in plasma volume and induce an
      impairment of cardiovascular regulatory mechanisms. Identification of the most
      susceptible patients and of the various risk factors may contribute to
      significantly improve cardiovascular stability during dialysis. In some high-risk
      patients, monitoring and biofeedback of the various hemodynamic variables,
      together with an extensive use of convection, can prevent the appearance of
      symptomatic hypotension and help in averting its onset.

PMID- 16441872
TI  - Inflammation and dialysate quality.

PMID- 16441873
TI  - Clinical effects of online dialysate and infusion fluids.
AB  - Online hemodiafiltration appears to be the most effective technique of renal
      replacement therapy in many respects. Removal of small and high-molecular weight
      substances is enhanced. Modern technology ensures a safe, online production of
      reinfusion fluids. Nonetheless, stringent maintenance rules are required for the
      production of sterile and nonpyrogenic-dialysate solutions. In this review, we
      will critically review the state of the art of the clinical effects derived from
      the use of ultrapure dialysate and the online production of dialysate fluids in
      high-flux hemodiafiltration.

PMID- 16441874
TI  - Convection with conviction-online hemodiafiltration for all: single center
      clinical observations.
AB  - Online hemodiafiltration (HDF) has recently become an alternative to conventional
      hemodialysis for treatment of end-stage renal disease with superior results.
      Clinical experience with HDF in unselected populations has not been widely
      published and a longitudinal study on such a group of patients is presented here.

PMID- 16441875
TI  - Querying the public databases for sequences using complex keywords contained in
      the feature lines.
AB  - BACKGROUND: High throughput technologies often require the retrieval of large
      data sets of sequences. Retrieval of EMBL or GenBank entries using keywords is
      easy using tools such as ACNUC, Entrez or SRS, but has some limitations, in
      particular when querying with complex keywords. RESULTS: We show that Entrez has
      severe limitations with respect to retrieving subsequences. SRS works well with
      simple keywords but not with keywords composed of several terms, and has problems
      with complex queries. ACNUC works well, but does not allow precise queries in the
      Feature qualifiers. We developed specific Perl scripts to precisely retrieve
      subsequences as defined by complex descriptors in the Features qualifiers of the
      EMBL entries. We improved parts of the bioPerl library to allow parsing of large
      data files, and we embedded these scripts in a user friendly interface (OS
      independent) for easy use. CONCLUSION: Although not as fast as the public tools
      that use prebuilt indexes, parsing the complete entries using a script is often
      necessary in order to retrieve the exact data searched for. Embedding in a user
      friendly interface allows biologists to use the scripts, which can easily be
      modified, if necessary, by bioinformaticians for unforeseen needs.

PMID- 16441876
TI  - Room for improvement? A survey of the methods used in systematic reviews of
      adverse effects.
AB  - BACKGROUND: Although the methods for conducting systematic reviews of efficacy
      are well established, there is much less guidance on how systematic reviews of
      adverse effects should be performed. METHODS: In order to determine where
      methodological research is most needed to improve systematic reviews of adverse
      effects of health care interventions, we conducted a descriptive analysis of
      systematic reviews published between 1994 and 2005. We searched the Database of
      Abstracts of Reviews of Effects (DARE) and The Cochrane Database of Systematic
      Reviews (CDSR) to identify systematic reviews in which the primary outcome was an
      adverse effect or effects. We then extracted data on many of the elements of the
      systematic review process including: types of interventions studied, adverse
      effects of interest, resources searched, search strategies, data sources included
      in reviews, quality assessment of primary data, nature of the data analysis, and
      source of funding. RESULTS: 256 reviews were included in our analysis, of which
      the majority evaluated drug interventions and pre-specified the adverse effect or
      effects of interest. A median of 3 resources were searched for each review and
      very few reviews (13/256) provided sufficient information to reproduce their
      search strategies. Although more than three quarters (185/243) of the reviews
      sought to include data from sources other than randomised controlled trials,
      fewer than half (106/256) assessed the quality of the studies that were included.
      Data were pooled quantitatively in most of the reviews (165/256) but
      heterogeneity was not always considered. Less than half (123/256) of the reviews
      reported on the source of funding. CONCLUSION: There is an obvious need to
      improve the methodology and reporting of systematic reviews of adverse effects.
      The methodology around identification and quality assessment of primary data is
      the main concern.

PMID- 16441877
TI  - Identification of major cell types in paraffin sections of bovine tissues.
AB  - BACKGROUND: Identification of cell types in bovine tissue sections is complicated
      by the limited availability of anti-bovine antibodies, and by antigen retrieval
      treatments required for formalin-fixed tissue samples. We have evaluated an
      antibody and lectin panel for identifying major cell types in paraffin-embedded
      bovine tissue sections, and report optimized pretreatments for these markers.
      RESULTS: We selected 31 useful antibodies and lectins which can be used to
      identify cell types of epithelia, connective tissue, muscle, and nervous tissue,
      as well as cell proliferation and apoptosis. CONCLUSION: The panel of markers
      allows the identification of all major cell types in paraffin-embedded cattle
      tissue sections by immunohistochemistry or lectin histochemistry. Heat-induced
      epitope retrieval methods are required for most antibodies.

PMID- 16441878
TI  - Fetal intestinal fibroblasts respond to insulin-like growth factor (IGF)-II
      better than adult intestinal fibroblasts.
AB  - BACKGROUND: We compared IGF responses of fetal and adult intestinal fibroblasts
      to identify a developmental difference in the IGF-axis. Intestinal fibroblasts
      were isolated from maternal and fetal jejunum. Media was conditioned at
      confluence and one week afterwards. The proliferative response at confluence to 5
      nM IGF-I or -II was compared. RESULTS: There were no significant differences in
      IGFBP expression at confluence. Post-confluence, fetal fibroblasts had no
      significant changes in IGFBP-2 and IGFBP-3 expression. Post-confluent maternal
      fibroblasts had increased IGFBP-3 levels that were significant compared to the
      fetal fibroblasts. IGF-I increased in post-confluent fetal fibroblasts, while in
      maternal fibroblasts it decreased (p < 0.001). IGF-II secretion decreased
      significantly in post-confluent maternal fibroblasts (p < 0.05). Maternal
      fibroblasts proliferated more with IGF-I than IGF-II (p < 0.001). Fetal
      fibroblasts responded to IGF-II slightly better than IGF-I and significantly
      greater than maternal cells (p < 0.001). CONCLUSION: Fetal intestinal fibroblasts
      respond to IGF-II with greater proliferation and do not have the increased IGFBPs
      seen post-confluence in adult intestinal fibroblasts.

PMID- 16441879
TI  - Causal analysis of case-control data.
AB  - In a series of papers, Robins and colleagues describe inverse probability of
      treatment weighted (IPTW) estimation in marginal structural models (MSMs), a
      method of causal analysis of longitudinal data based on counterfactual
      principles. This family of statistical techniques is similar in concept to
      weighting of survey data, except that the weights are estimated using study data
      rather than defined so as to reflect sampling design and post-stratification to
      an external population. Several decades ago Miettinen described an elementary
      method of causal analysis of case-control data based on indirect standardization.
      In this paper we extend the Miettinen approach using ideas closely related to
      IPTW estimation in MSMs. The technique is illustrated using data from a case
      control study of oral contraceptives and myocardial infarction.

PMID- 16441881
TI  - Identification of metabolic system parameters using global optimization methods.
AB  - BACKGROUND: The problem of estimating the parameters of dynamic models of complex
      biological systems from time series data is becoming increasingly important.
      METHODS AND RESULTS: Particular consideration is given to metabolic systems that
      are formulated as Generalized Mass Action (GMA) models. The estimation problem is
      posed as a global optimization task, for which novel techniques can be applied to
      determine the best set of parameter values given the measured responses of the
      biological system. The challenge is that this task is nonconvex. Nonetheless,
      deterministic optimization techniques can be used to find a global solution that
      best reconciles the model parameters and measurements. Specifically, the paper
      employs branch-and-bound principles to identify the best set of model parameters
      from observed time course data and illustrates this method with an existing model
      of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively
      simple yet representative system with five dependent states and a total of 19
      unknown parameters of which the values are to be determined. CONCLUSION: The
      efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae
      example. The method described in this paper is likely to be widely applicable in
      the dynamic modeling of metabolic networks.

PMID- 16441880
TI  - Reservoir cells no longer detectable after a heterologous SHIV challenge with the
      synthetic HIV-1 Tat Oyi vaccine.
AB  - BACKGROUND: Extra-cellular roles of Tat might be the main cause of maintenance of
      HIV-1 infected CD4 T cells or reservoir cells. We developed a synthetic vaccine
      based on a Tat variant of 101 residues called Tat Oyi, which was identified in
      HIV infected patients in Africa who did not progress to AIDS. We compared, using
      rabbits, different adjuvants authorized for human use to test on ELISA the
      recognition of Tat variants from the five main HIV-1 subtypes. A formulation was
      tested on macaques followed by a SHIV challenge with a European strain. RESULTS:
      Tat Oyi with Montanide or Calcium Phosphate gave rabbit sera able to recognize
      all Tat variants. Five on seven Tat Oyi vaccinated macaques showed a better
      control of viremia compared to control macaques and an increase of CD8 T cells
      was observed only on Tat Oyi vaccinated macaques. Reservoir cells were not
      detectable at 56 days post-challenge in all Tat Oyi vaccinated macaques but not
      in the controls. CONCLUSION: The Tat Oyi vaccine should be efficient worldwide.
      No toxicity was observed on rabbits and macaques. We show in vivo that antibodies
      against Tat could restore the cellular immunity and make it possible the
      elimination of reservoir cells.

PMID- 16441883
TI  - Serum level of semicarbazide-sensitive amine oxidase in children with ADHD.
AB  - BACKGROUND: The objective of this study was to analyze the extracellularly acting
      semicarbazide-sensitive amine oxidase (SSAO) serum levels in children with ADHD
      for the first time. SSAO is known to show deviations from normal in various
      somatic disorders and to interplay with the intracellularly active MAO. In humans
      two forms of SSAO a circulating form in plasma and a membrane-bound form are
      involved in monoaminergic metabolism. METHODS: We analyzed serum levels of SSAO
      in 27 children meeting ICD-10 criteria of Hyperkinetic Disorder (F90) or DSM-IV
      criteria of ADHD combined type by HPLC method and fluorimetric detection. A group
      of 42 healthy volunteers within the same age range (7.0 - 14.0 years) served as
      controls. RESULTS: No significant differences between children with ADHD (SSAO
      activity M = 773, SD = 217 mU/l) and healthy controls (SSAO activity M = 775, SD
      = 256 mU/l) in SSAO serum levels were found (F = 2.18; p > 0.14). Further,
      stimulant medication status had no influence on the result (F = 2.52; p > 0.11).
      CONCLUSION: There is no evidence for a deviation of SSAO serum activity in ADHD.
      Hence, extracellularly acting SSAO does not seem to be a promising factor for
      further research in ADHD. But progress in knowledge of its physiologic role and
      of the relationship between the membrane-bound and the circulating serum form may
      open new avenues for research on SSAO in ADHD.

PMID- 16441882
TI  - The Mayer-Rokitansky-Kuster-Hauser syndrome (congenital absence of uterus and
      vagina)--phenotypic manifestations and genetic approaches.
AB  - The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome affects at least 1 out of 4500
      women and has for a long time been considered as a sporadic anomaly. Congenital
      absence of upper vagina and uterus is the prime feature of the disease which, in
      addition, is often found associated with unilateral renal agenesis or adysplasia
      as well as skeletal malformations (MURCS association). The phenotypic
      manifestations of MRKH overlap various other syndromes or associations and thus
      require accurate delineation. Since MRKH manifests itself in males, the term GRES
      syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied
      to both sexes. The MRKH syndrome, when described in familial aggregates, seems to
      be transmitted as an autosomal dominant trait with an incomplete degree of
      penetrance and variable expressivity. This suggests the involvement of either
      mutations in a major developmental gene or a limited chromosomal deletion. Until
      recently progress in understanding the genetics of MRKH syndrome has been slow,
      however, now HOX genes have been shown to play key roles in body patterning and
      organogenesis, and in particular during genital tract development. Expression
      and/or function defects of one or several HOX genes may account for this
      syndrome.

PMID- 16441884
TI  - Rapid and asymmetric divergence of duplicate genes in the human gene coexpression
      network.
AB  - BACKGROUND: While gene duplication is known to be one of the most common
      mechanisms of genome evolution, the fates of genes after duplication are still
      being debated. In particular, it is presently unknown whether most duplicate
      genes preserve (or subdivide) the functions of the parental gene or acquire new
      functions. One aspect of gene function, that is the expression profile in gene
      coexpression network, has been largely unexplored for duplicate genes. RESULTS:
      Here we build a human gene coexpression network using human tissue-specific
      microarray data and investigate the divergence of duplicate genes in it. The
      topology of this network is scale-free. Interestingly, our analysis indicates
      that duplicate genes rapidly lose shared coexpressed partners: after
      approximately 50 million years since duplication, the two duplicate genes in a
      pair have only slightly higher number of shared partners as compared with two
      random singletons. We also show that duplicate gene pairs quickly acquire new
      coexpressed partners: the average number of partners for a duplicate gene pair is
      significantly greater than that for a singleton (the latter number can be used as
      a proxy of the number of partners for a parental singleton gene before
      duplication). The divergence in gene expression between two duplicates in a pair
      occurs asymmetrically: one gene usually has more partners than the other one. The
      network is resilient to both random and degree-based in silico removal of either
      singletons or duplicate genes. In contrast, the network is especially vulnerable
      to the removal of highly connected genes when duplicate genes and singletons are
      considered together. CONCLUSION: Duplicate genes rapidly diverge in their
      expression profiles in the network and play similar role in maintaining the
      network robustness as compared with singletons.

PMID- 16441886
TI  - Word Processing differences between dyslexic and control children.
AB  - BACKGROUND: The aim of this study was to investigate brain responses triggered by
      different wordclasses in dyslexic and control children. The majority of dyslexic
      children have difficulties to phonologically assemble a word from sublexical
      parts following grapheme-to-phoneme correspondences. Therefore, we hypothesised
      that dyslexic children should mainly differ from controls processing low frequent
      words that are unfamiliar to the reader. METHODS: We presented different
      wordclasses (high and low frequent words, pseudowords) in a rapid serial visual
      word (RSVP) design and performed wavelet analysis on the evoked activity.
      RESULTS: Dyslexic children had lower evoked power amplitudes and a higher
      spectral frequency for low frequent words compared to control children. No group
      differences were found for high frequent words and pseudowords. Control children
      had higher evoked power amplitudes and a lower spectral frequency for low
      frequent words compared to high frequent words and pseudowords. This pattern was
      not present in the dyslexic group. CONCLUSION: Dyslexic children differed from
      control children only in their brain responses to low frequent words while
      showing no modulated brain activity in response to the three word types. This
      might support the hypothesis that dyslexic children are selectively impaired
      reading words that require sublexical processing. However, the lacking
      differences between word types raise the question if dyslexic children were able
      to process the words presented in rapid serial fashion in an adequate way.
      Therefore the present results should only be interpreted as evidence for a
      specific sublexical processing deficit with caution.

PMID- 16441887
TI  - Changes in Health Related Quality of Life 3 months after an acute coronary
      syndrome.
AB  - BACKGROUND: The aim of the study was to identify the changes in Health Related
      Quality of Life (HRQL) 3 months after discharge from hospital, in patients who
      have had an acute coronary episode, and to determine the clinical and
      sociodemographic variables that explain those changes. METHODS: HRQL was assessed
      in 132 patients while they were admitted to the hospital and at 3 months after
      discharge, using the SF-36 health questionnaire. To identify the variables
      associated with the change, multiple linear regression models were constructed
      for two summary dimensions of the SF-36 (PCS and MCS) taking the change in the
      score of the dimension as dependent variable. RESULTS: There were no significant
      differences between the patients who completed the monitoring (n = 76) and those
      who were dropped out. After three months, a significant decrease was observed in
      the dimensions of physical functioning, general health, vitality, and Physical
      Summary Component (PCS). The variables revascularisation, age, and the
      interaction between previous history of coronary heart disease (CHD) and the
      presence of one or more risk factors explained 16.6% of the decrease in the PCS.
      The decrease in the PCS was 6.4 points less in the patients who had undergone
      revascularisation, 0.2 points less for each year of age, and 4.7 points less in
      the patients who had antecedents of the illness as well as one or more risk
      factors. CONCLUSION: The dimensions most affected at three months after an acute
      coronary episode were those related to the physical component. Undergoing
      revascularisation improved the PCS in patients, but in the younger patients and
      those without personal antecedents or risk factors, the PCS was affected more,
      perhaps due to greater expectations for recovery in these patients.

PMID- 16441888
TI  - Neonatal jaundice and its management: knowledge, attitude and practice of
      community health workers in Nigeria.
AB  - BACKGROUND: Neonatal jaundice (NNJ) is still a leading cause of preventable brain
      damage, physical and mental handicap, and early death among infants in many
      communities. Greater awareness is needed among all health workers. The objective
      of the study was to assess the knowledge of primary health care workers about the
      description, causes, effective treatment, and sequelae of NNJ. METHODS: The
      setting was a local government area i.e. an administrative district within the
      south-western part of Nigeria. Community health workers in this area were
      interviewed by means of a self-administered questionnaire which focused on
      awareness and knowledge of neonatal jaundice and its causes, treatment and
      complications. RESULTS: Sixty-six community health workers participated in the
      survey and male-to-female ratio was 1:5. Their work experience averaged 13.5 (SD
      12.7) years. Only 51.5% of the respondents gave a correct definition of NNJ. 75.8
      % knew how to examine for this condition while 84.9 % knew at least two of its
      major causes in our environment. Also, only 54.5 % had adequate knowledge of
      effective treatment namely, phototherapy and exchange blood transfusion. Rather
      than referring affected babies to hospitals for proper management, 13.4 %, 10.4 %
      and 3 % of the participants would treat with ineffective drugs, natural
      phototherapy and herbal remedies respectively. None of the participants knew any
      effective means of prevention. CONCLUSION: Primary health care workers may have
      inadequate knowledge and misconceptions on NNJ which must be addressed
      concertedly before the impact of the condition on child health and well-being can
      be significantly reduced. We recommend regular training workshops and seminars
      for this purpose.

PMID- 16441889
TI  - Pain in elderly people with severe dementia: a systematic review of behavioural
      pain assessment tools.
AB  - BACKGROUND: Pain is a common and major problem among nursing home residents. The
      prevalence of pain in elderly nursing home people is 40-80%, showing that they
      are at great risk of experiencing pain. Since assessment of pain is an important
      step towards the treatment of pain, there is a need for manageable, valid and
      reliable tools to assess pain in elderly people with dementia. METHODS: This
      systematic review identifies pain assessment scales for elderly people with
      severe dementia and evaluates the psychometric properties and clinical utility of
      these instruments. Relevant publications in English, German, French or Dutch,
      from 1988 to 2005, were identified by means of an extensive search strategy in
      Medline, Psychinfo and CINAHL, supplemented by screening citations and
      references. Quality judgement criteria were formulated and used to evaluate the
      psychometric aspects of the scales. RESULTS: Twenty-nine publications reporting
      on behavioural pain assessment instruments were selected for this review. Twelve
      observational pain assessment scales (DOLOPLUS2; ECPA; ECS; Observational Pain
      Behavior Tool; CNPI; PACSLAC; PAINAD; PADE; RaPID; Abbey Pain Scale; NOPPAIN;
      Pain assessment scale for use with cognitively impaired adults) were identified.
      Findings indicate that most observational scales are under development and show
      moderate psychometric qualities. CONCLUSION: Based on the psychometric qualities
      and criteria regarding sensitivity and clinical utility, we conclude that PACSLAC
      and DOLOPLUS2 are the most appropriate scales currently available. Further
      research should focus on improving these scales by further testing their
      validity, reliability and clinical utility.

PMID- 16441890
TI  - Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human
      volunteers after ingestion of maritime pine bark extract (Pycnogenol).
AB  - French maritime pine bark extract (Pycnogenol) displays a variety of anti
      inflammatory effects in vivo. Aim of this study was to determine whether human
      plasma after oral intake of Pycnogenol contains sufficient concentrations of
      active principles to inhibit key mediators of inflammation. Blood samples from
      seven healthy volunteers were obtained before and after five days administration
      of 200 mg Pycnogenol per day. Plasma samples statistically significantly
      inhibited matrix metalloproteinase 9 (MMP-9) release from human monocytes and NF
      kappaB activation. Thus, we provide evidence that bioavailable active principles
      of Pycnogenol exert anti-inflammatory effects by inhibition of proinflammatory
      gene expression which is consistent with documented clinical observations. We
      suggest that our ex vivo method is suitable to substantiate molecular
      pharmacological mechanisms of complex plant extracts in a more focussed and
      rational way compared to in vitro studies by taking into account the processes of
      absorption and metabolism.

PMID- 16441891
TI  - Color naming deficits and attention-deficit/hyperactivity disorder: a retinal
      dopaminergic hypothesis.
AB  - BACKGROUND: Individuals with Attention-Deficit/Hyperactive Disorder (ADHD) have
      unexplained difficulties on tasks requiring speeded processing of colored
      stimuli. Color vision mechanisms, particularly short-wavelength (blue-yellow)
      pathways, are highly sensitive to various diseases, toxins and drugs that alter
      dopaminergic neurotransmission. Thus, slow color processing might reflect subtle
      impairments in the perceptual encoding stage of stimulus color, which arise from
      hypodopaminergic functioning. PRESENTATION OF HYPOTHESES: 1) Color perception of
      blue-yellow (but not red-green) stimuli is impaired in ADHD as a result of
      deficient retinal dopamine; 2) Impairments in the blue-yellow color mechanism in
      ADHD contribute to poor performance on speeded color naming tasks that include a
      substantial proportion of blue-yellow stimuli; and 3) Methylphenidate increases
      central dopamine and is also believed to increase retinal dopamine, thereby
      normalizing blue-yellow color perception, which in turn improves performance on
      the speeded color naming tasks. TESTING THE HYPOTHESIS: Requires three
      approaches, including:1) direct assessment of color perception in individuals
      with ADHD to determine whether blue-yellow color perception is selectively
      impaired; 2) determination of relationship between performance on
      neuropsychological tasks requiring speeded color processing and color perception;
      and 3) randomized, controlled pharmacological intervention with stimulant
      medication to examine the effects of enhancing central dopamine on color
      perception and task performance IMPLICATIONS OF HYPOTHESIS: If substantiated, the
      findings of color perception problems would necessitate a re-consideration of
      current neuropsychological models of attention-deficit/hyperactivity disorder,
      guide psycho-education, academic instruction, and require consideration of
      stimulus color in many of the widely used neuropsychological tests.

PMID- 16441892
TI  - Tracking and prevalence of cardiovascular disease risk factors across socio
      economic classes: a longitudinal substudy of the European Youth Heart Study.
AB  - BACKGROUND: The highest prevalence of several cardiovascular disease risk factors
      including obesity, smoking and low physical activity level is observed in adults
      of low socioeconomic status. This study investigates whether tracking of body
      mass index and physical fitness from childhood to adolescence differs between
      groups of socioeconomic status. Furthermore the study investigates whether social
      class differences in the prevalence of overweight and low physical fitness exist
      or develop within the age range from childhood to adolescence. METHODS: In all,
      384 school children were followed for a period of six years (from third to ninth
      grade). Physical fitness was determined by a progressive maximal cycle ergometer
      test and the classification of overweight was based on body mass index cut-points
      proposed by the International Obesity Task Force. Socioeconomic status was
      defined according to The International Standard Classification of Occupation
      scheme. RESULTS: Moderate and moderately high tracking was observed for physical
      fitness and body mass index, respectively. No significant difference in tracking
      was observed between groups of socioeconomic status. A significant social
      gradient was observed in both the prevalence of overweight and low physical
      fitness in the 14-16-year-old adolescents, whereas at the age of 8-10 years, only
      the prevalence of low physical fitness showed a significant inverse relation to
      socioeconomic status. The odds of both developing and maintaining risk during the
      measurement period were estimated as bigger in the group of low socioeconomic
      status than in the group of high socioeconomic status, although differences were
      significant only with respect to the odds of developing overweight. CONCLUSION:
      The results indicate that the fundamental possibilities of predicting overweight
      and low physical fitness at an early point in time are the same for different
      groups of socio-economic status. Furthermore, the observed development of social
      inequalities in the absolute prevalence of overweight and low physical fitness
      underline the need for broad preventive efforts targeting children of low
      socioeconomic status in early childhood.

PMID- 16441893
TI  - Assessment of balance and risk for falls in a sample of community-dwelling adults
      aged 65 and older.
AB  - BACKGROUND: Falls are a major health concern for older adults and their impact is
      a significant public health problem. The chief modifiable risk factors for falls
      in community-dwellers are psychotropic drugs, polypharmacy, environmental
      hazards, poor vision, lower extremity impairments, and balance impairments. This
      study focused on balance impairments. Its purpose was to assess the feasibility
      of recruiting older adults with possible balance problems for research conducted
      at a chiropractic research center, and to explore the utility of several widely
      used balance instruments for future studies of the effect of chiropractic care on
      balance in older adults. METHODS: This descriptive study was conducted from
      September through December 2004. Participants were recruited through a variety of
      outreach methods, and all were provided with an educational intervention. Data
      were collected at each of two visits through questionnaires, interviews, and
      physical examinations. Balance was assessed on both visits using the Activities
      specific Balance Confidence Scale (ABCS), the Berg Balance Scale (BBS), and the
      One Leg Standing Test (OLST). RESULTS: A total of 101 participants enrolled in
      the study. Advertising in the local senior newspaper was the most effective
      method of recruitment (46%). The majority of our participants were white (86%)
      females (67%). About one third (32%) of participants had a baseline BBS score
      below 46, the cut-off point for predicting risk of falling. A mean improvement in
      BBS scores of 1.7 points was observed on the second visit. For the subgroup with
      baseline scores below 46, the mean change was 4.5 points, but the group mean
      remained below 46 (42.5). CONCLUSION: Recruitment of community-dwelling seniors
      for fall-related research conducted at a chiropractic research center appears
      feasible, and the most successful recruitment strategies for this center appeared
      to be a combination of targeted newspaper ads and personal contact through senior
      centers. The BBS and OLST appear to be promising screening and assessment
      instruments, which might have utility in future investigations of the possible
      effects of chiropractic care on balance.

PMID- 16441894
TI  - Effect of zooming on texture features of ultrasonic images.
AB  - BACKGROUND: Unstable carotid plaques on subjective, visual, assessment using B
      mode ultrasound scanning appear as echolucent and heterogeneous. Although
      previous studies on computer assisted plaque characterisation have standardised B
      mode images for brightness, improving the objective assessment of echolucency,
      little progress has been made towards standardisation of texture analysis
      methods, which assess plaque heterogeneity. The aim of the present study was to
      investigate the influence of image zooming during ultrasound scanning on textural
      features and to test whether or not resolution standardisation decreases the
      variability introduced. METHODS: Eighteen still B-mode images of carotid plaques
      were zoomed during carotid scanning (zoom factor 1.3) and both images were
      transferred to a PC and normalised. Using bilinear and bicubic interpolation, the
      original images were interpolated in a process of simulating off-line zoom using
      the same interpolation factor. With the aid of the colour-coded image, carotid
      plaques of the original, zoomed and two resampled images for each case were
      outlined and histogram, first order and second order statistics were subsequently
      calculated. RESULTS: Most second order statistics (21/25, 84%) were significantly
      (p < 0.05) sensitive to image zooming during scanning, in contrast to histogram
      and first order statistics (4/25, 16%, p < 0.001, Fisher's exact test). Median
      (interquartile range) change of those features sensitive to zooming was 18.14%
      (4.94-28.43). Image interpolation restored these changes, the bicubic
      interpolation being superior compared to bilinear interpolation (p = 0.036).
      CONCLUSION: Texture analysis of ultrasonic plaques should be performed under
      standardised resolution settings; otherwise a resolution normalisation algorithm
      should be applied.

PMID- 16441895
TI  - Exploration of auditory P50 gating in schizophrenia by way of difference waves.
AB  - Electroencephalographic measures of information processing encompass both mid
      latency evoked potentials like the pre-attentive auditory P50 potential and a
      host of later more cognitive components like P300 and N400.Difference waves have
      mostly been employed in studies of later event related potentials but here this
      method along with low frequency filtering is applied exploratory on auditory P50
      gating data, previously analyzed in the standard format (reported in Am J
      Psychiatry 2003, 160:2236-8). The exploration was motivated by the observation
      during visual peak detection that the AEP waveform was different in the patient
      group, although this was not reflected by the peak measures. The sample included
      un-medicated schizophrenia spectrum patients (n = 17) and healthy controls (n =
      24). The patients had an attenuated difference P50. This attenuation was
      primarily seen in the sub-sample of patients with severe negative symptoms. The
      difference attenuation was due to low amplitude at the first stimulus. This
      suggests an abnormality in readiness more than an abnormality in gating in the
      patient group.

PMID- 16441896
TI  - Differential regulation of neurotrophin expression in human bronchial smooth
      muscle cells.
AB  - BACKGROUND: Human bronchial smooth muscle cells (HBSMC) may regulate airway
      inflammation by secreting cytokines, chemokines and growth factors. The
      neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF) and neurotrophin-3 (NT-3), have been shown to be elevated during
      airway inflammation and evoke airway hyperresponsiveness. We studied if HBSMC may
      be a source of NGF, BDNF and NT-3, and if so, how inflammatory cytokines may
      influence their production. METHODS: Basal and cytokine (IL-1beta, IFN-gamma, IL
      4)-stimulated neurotrophin expression in HBSMC cultured in vitro was quantified.
      The mRNA expression was quantified by real-time RT-PCR and the protein secretion
      into the cell culture medium by ELISA. RESULTS: We observed a constitutive NGF,
      BDNF and NT-3 expression. IL-1beta stimulated a transient increase of NGF, while
      the increase of BDNF had a later onset and was more sustained. COX-inhibitors
      (indomethacin and NS-398) markedly decreased IL-1beta-stimulated secretion of
      BDNF, but not IL-1beta-stimulated NGF secretion. IFN-gamma increased NGF
      expression, down-regulated BDNF expression and synergistically enhanced IL-1beta
      stimulated NGF expression. In contrast, IL-4 had no effect on basal NGF and BDNF
      expression, but decreased IL-1beta-stimulated NGF expression. NT-3 was not
      altered by the tested cytokines. CONCLUSION: Taken together, our data indicate
      that, in addition to the contractile capacity, HBSMC can express NGF, BDNF and NT
      3. The expression of these neurotrophins may be differently regulated by
      inflammatory cytokines, suggesting a dynamic interplay that might have a
      potential role in airway inflammation.

PMID- 16441897
TI  - Lactate production yield from engineered yeasts is dependent from the host
      background, the lactate dehydrogenase source and the lactate export.
AB  - BACKGROUND: Metabolic pathway manipulation for improving the properties and the
      productivity of microorganisms is becoming a well established concept. For the
      production of important metabolites, but also for a better understanding of the
      fundamentals of cell biology, detailed studies are required. In this work we
      analysed the lactate production from metabolic engineered Saccharomyces
      cerevisiae cells expressing a heterologous lactate dehydrogenase (LDH) gene. The
      LDH gene expression in a budding yeast cell introduces a novel and alternative
      pathway for the NAD+ regeneration, allowing a direct reduction of the
      intracellular pyruvate to lactate, leading to a simultaneous accumulation of
      lactate and ethanol. RESULTS: Four different S. cerevisiae strains were
      transformed with six different wild type and one mutagenised LDH genes, in
      combination or not with the over-expression of a lactate transporter. The
      resulting yield values (grams of lactate produced per grams of glucose consumed)
      varied from as low as 0,0008 to as high as 0.52 g g-1. In this respect, and to
      the best of our knowledge, higher redirections of the glycolysis flux have never
      been obtained before without any disruption and/or limitation of the competing
      biochemical pathways. CONCLUSION: In the present work it is shown that the
      redirection of the pathway towards the lactate production can be strongly
      modulated by the genetic background of the host cell, by the source of the
      heterologous Ldh enzyme, by improving its biochemical properties as well as by
      modulating the export of lactate in the culture media.

PMID- 16441898
TI  - Stable evolutionary signal in a yeast protein interaction network.
AB  - BACKGROUND: The recently emerged protein interaction network paradigm can provide
      novel and important insights into the innerworkings of a cell. Yet, the heavy
      burden of both false positive and false negative protein-protein interaction data
      casts doubt on the broader usefulness of these interaction sets. Approaches
      focusing on one-protein-at-a-time have been powerfully employed to demonstrate
      the high degree of conservation of proteins participating in numerous
      interactions; here, we expand his 'node' focused paradigm to investigate the
      relative persistence of 'link' based evolutionary signals in a protein
      interaction network of S. cerevisiae and point out the value of this relatively
      untapped source of information. RESULTS: The trend for highly connected proteins
      to be preferably conserved in evolution is stable, even in the context of
      tremendous noise in the underlying protein interactions as well as in the
      assignment of orthology among five higher eukaryotes. We find that local
      clustering around interactions correlates with preferred evolutionary
      conservation of the participating proteins; furthermore the correlation between
      high local clustering and evolutionary conservation is accompanied by a stable
      elevated degree of coexpression of the interacting proteins. We use this
      conserved interaction data, combined with P. falciparum/Yeast orthologs, as proof
      of-principle that high-order network topology can be used comparatively to deduce
      local network structure in non-model organisms. CONCLUSION: High local clustering
      is a criterion for the reliability of an interaction and coincides with preferred
      evolutionary conservation and significant coexpression. These strong and stable
      correlations indicate that evolutionary units go beyond a single protein to
      include the interactions among them. In particular, the stability of these
      signals in the face of extreme noise suggests that empirical protein interaction
      data can be integrated with orthologous clustering around these protein
      interactions to reliably infer local network structures in non-model organisms.

PMID- 16441900
TI  - Molecular methods for assessing insect parasitism.
AB  - Determining insect parasitism rates is problematic due to the small size and lack
      of useful distinguishing morphological characters of many parasitoid taxa. To
      solve this problem, entomologists have employed one of four general methods to
      detect parasitoid protein or nucleic acid markers: serological assay; random
      amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR); allozyme
      electrophoresis; or specific PCR. Serological methods, especially with monoclonal
      antibodies, are unrivalled for specificity, enabling discrimination at the stage
      as well as species level. However, they have not found favour with many workers,
      possibly due to complexity and expense. RAPD-PCR has been widely used, but can
      only be recommended for restricted applications because of its poor
      reproducibility. Allozyme electrophoresis provides reproducible detection and
      discrimination of closely related species. Specific-PCR is highly specific and
      reproducible, and also has the shortest latency for detection, usually 24 h or
      less after parasitization. The substantial existing literature on allozyme
      electrophoresis and specific PCR is used to support recommendations on what are
      apt to be fruitful enzyme systems or genomic regions for detecting and
      discriminating parasitoids in untried parasitoid-host assemblages.

PMID- 16441901
TI  - Response of the polyphagous whitefly Bemisia tabaci B-biotype (Hemiptera:
      Aleyrodidae) to crop diversification - influence of multiple sensory stimuli on
      activity and fecundity.
AB  - A fundamental question concerning crop diversification is which mechanisms
      determine pest population size in polycultures compared to monocultures. It has
      been proposed that polyphagous insects experience a difficulty in decision-making
      when selecting food and oviposition sites in the presence of different host
      plants. This hypothesis was tested in the extremely polyphagous whitefly Bemisia
      tabaci (Gennadius) B-biotype, where behaviour (movement) and fecundity of females
      were compared in choice and no-choice experiments in the laboratory. Two parallel
      tests, one on different crops, including cucumber, bean and tomato, and one on
      different tomato cultivars, were conducted using both a mixture of crops and of
      tomato cultivars, as opposed to the same crop or cultivar respectively. Bemisia
      tabaci showed a distinct behavioural preference for cucumber when exposed to
      different crops simultaneously suggesting that B. tabaci has no difficulty in
      choosing a host plant, i.e. in making a decision, when one of the plants offered
      in the choice test is a high-ranking host plant. Conversely, when only low
      ranking hosts of similar, but not identical, signatures were present, female
      whiteflies appeared to have difficulty in making a decision, resulting in
      increased movement and reduced fecundity. This is consistent with both the
      hypothesis that polyphagous insects have a problem selecting a host plant when
      given multiple choices and with the hierarchy threshold model, under which egg
      loads are lessened between periods of searching for better host plants. The study
      illustrates how insect behaviour can be affected by inter-cropping not only with
      different crops, but also with different cultivars of the same crop, thus
      potentially providing a simple and efficient way of reducing whitefly population
      build-up.

PMID- 16441899
TI  - Globalization, migration health, and educational preparation for transnational
      medical encounters.
AB  - Unprecedented migration, a core dimension of contemporary globalization,
      challenges population health. In a world of increasing human mobility, many
      health outcomes are shaped by transnational interactions among care providers and
      care recipients who meet in settings where nationality/ethnic match is not an
      option. This review article explores the value of transnational competence (TC)
      education as preparation for ethnically and socially discordant clinical
      encounters. The relevance of TC's five core skill domains (analytic, emotional,
      creative, communicative, and functional) for migration health and the medical
      school curriculum is elaborated. A pedagogical approach that prepares for the
      transnational health-care consultation is presented, with a focus on clinical
      clerkship learning experiences. Educational preparation for contemporary medical
      encounters needs to include a comprehensive set of patient-focused interpersonal
      skills, be adaptable to a wide variety of service users and global practice
      sites, and possess utility in addressing both the quality of patient care and
      socio-political constraints on migration health.

PMID- 16441902
TI  - Oviposition responses to patch quality in the larch ladybird Aphidecta obliterata
      (Coleoptera: Coccinellidae): effects of aphid density, and con- and
      heterospecific tracks.
AB  - The effects and persistence of oviposition-deterring semiochemical cues from
      conspecific and heterospecific larval tracks on the oviposition rate of Aphidecta
      obliterata (Linnaeus) females were investigated. In addition, the effects of
      varying aphid prey density were considered and also whether any resulting
      response originated from differential nutritional status of females and/or due to
      aphid odour stimuli. The existence of oviposition responses to conspecific egg
      chemicals was also considered. Gravid A. obliterata females were deterred from
      oviposition by conspecific larval tracks and the effect was density dependent.
      Females actively avoided searching in these contaminated areas. Tracks induced a
      significant effect on oviposition for up to three days. Heterospecific tracks of
      the coccinellid Adalia bipunctata (Fabricius) or the chrysopid Chrysoperla carnea
      (Stephens) did not induce any oviposition response in A. obliterata females.
      Increasing aphid density induced increased oviposition rate in A. obliterata
      females. Nutritional status of females was an important factor in the
      relationship between aphid density and oviposition rate, but aphid associated
      cues (odours) were not. There was an inhibitory effect of extracts of conspecific
      egg-surface chemicals on oviposition by A. obliterata females. In the field,
      cannibalism, competition and limited food availability represent the major
      threats to egg and larval survival. Patch quality assessment mechanisms enable
      females to lay eggs at sites where offspring survival is maximized. Oviposition
      deterring semiochemicals tend to promote more even distribution of predators over
      prey patches.

PMID- 16441903
TI  - Oviposition deterrents for the Mediterranean fruit fly, Ceratitis capitata
      (Diptera: Tephritidae) from fly faeces extracts.
AB  - After oviposition, females of the Mediterranean fruit fly Ceratitis capitata
      Wiedemann deposit a host-marking pheromone on the fruit surface that deters
      oviposition by conspecifics. Methanolic extracts of fruit fly faeces elicit a
      similar deterrent effect. The results of laboratory and field experiments using
      raw methanolic extracts of C. capitata faeces as an oviposition deterrent are
      reported. Laboratory bioassays revealed a significant positive relationship
      between concentration of faeces and the inhibition of oviposition responses by C.
      capitata. Treatment of halves of coffee bushes with methanolic extracts
      containing 0.1, 1.0 and 10 mg faeces ml(-1) resulted in a significant reduction
      of infestation only at the highest concentration (P=0.03). Treatment of blocks of
      coffee bushes with an extract of 10 mg faeces ml(-1) resulted in an 84% reduction
      in infestation by C. capitata in sprayed plants and a 56% reduction in adjacent
      untreated coffee bushes surrounding treated plots, probably due to the deterrent
      effect of host-marking pheromone on fly oviposition. We conclude that faeces
      contain oviposition deterrent substances that effectively reduce fruit
      infestations by C. capitata, suggesting a clear potential for the use of this
      infochemical in integrated management programmes targeted at this pest.

PMID- 16441904
TI  - Effects of Galanthus nivalis agglutinin (GNA) expressed in tomato leaves on
      larvae of the tomato moth Lacanobia oleracea (Lepidoptera: Noctuidae) and the
      effect of GNA on the development of the endoparasitoid Meteorus gyrator
      (Hymenoptera: Braconidae).
AB  - The effect of ingestion of transgenic tomato leaves expressing the plant lectin
      Galanthus nivalis agglutinin (GNA) on development of larvae of Lacanobia oleracea
      (Linnaeus) was studied under laboratory conditions. When L. oleracea larvae were
      fed on tomato line 14.1H, expressing approximately 2.0% GNA, significant
      increases in the mean larval weight and in the amount of food consumed were
      found. This resulted in an overall reduction in the mean development time to the
      pupal stage of approximately 7 days. A significant increase in the percentage
      survival to the adult moth was also recorded when newly hatched larvae were
      reared on transgenic tomato leaves (72%) compared to larvae reared on
      untransformed leaves (40%). The effects of ingestion of GNA by L. oleracea
      larvae, via artificial diet or the leaves of transgenic tomato or potato plants,
      on the subsequent development of its solitary endoparasitoid Meteorus gyrator
      (Thunberg) was also studied. No significant effects on the life cycle parameters
      of M. gyrator developing in L. oleracea fed on GNA-containing diets were
      observed. Experiments with transgenic potato plants indicated that the stadium of
      the host larvae at parasitism had a greater influence on M. gyrator development
      than the presence of GNA. Potential GNA-binding glycoproteins were detected in
      the gut and body tissues of larval M. gyrator. Despite detection in host tissues,
      GNA could not be detected in adult M. gyrator and therefore it is likely that at
      the time of pupation M. gyrator are able to void the GNA in the meconial pellet.

PMID- 16441905
TI  - Identification of differentially expressed genes in brown planthopper Nilaparvata
      lugens (Hemiptera: Delphacidae) responding to host plant resistance.
AB  - The brown planthopper Nilaparvata lugens Stal is one of the major insect pests of
      rice Oryza sativa L. The host resistance exhibits profound effects on growth,
      development and propagation of N. lugens. To investigate the molecular response
      of N. lugens to host resistance, a cDNA-amplified fragment length polymorphism
      (cDNA-AFLP) technique was employed to identify the differentially expressed genes
      in the nymphs feeding on three rice varieties. Of the 2,800 cDNA bands analysed,
      54 were up-regulated and seven down-regulated qualitatively in N. lugens when the
      ingestion sources were changed from susceptible rice plants to resistant ones.
      Sequence analysis of the differential transcript-derived fragments showed that
      the genes involved in signalling, stress response, gene expression regulation,
      detoxification and metabolism were regulated by host resistance. Four of the
      transcript-derived fragments corresponding to genes encoding for a putative B
      subunit of phosphatase PP2A, a nemo kinase, a cytochrome P450 monooxygenase and a
      prolyl endopeptidase were further characterized in detail. Northern blot analysis
      confirmed that the expression of the four genes was enhanced in N. lugens feeding
      on resistant rice plants. The roles of these genes in the defensive response of
      N. lugens to host plant resistance were discussed.

PMID- 16441906
TI  - Occupancy-abundance models for predicting densities of three leaf beetles
      damaging the multipurpose tree Sesbania sesban in eastern and southern Africa.
AB  - Mesoplatys ochroptera Stal, Exosoma and Ootheca spp. seriously damage sesbania,
      Sesbania sesban (L.) Merril, a multipurpose leguminous tree widely used in
      tropical agroforestry. This is discouraging farmers from expanding the planting
      of sesbania in various agroforestry systems in eastern and south-central Africa.
      Rapid methods are needed for estimation of population densities of these beetles
      for decision making in pest management. A study was conducted with the objectives
      of determining the existence of any positive relationship between the occupancy
      and abundance of Mesoplatys, Exosoma and Ootheca and determining the model that
      best predicts abundance from occupancy for rapid estimation of population
      densities. The Poisson model assuming spatial randomness, the negative binomial
      distribution (NBD) model assuming spatial aggregation, the Nachman model without
      any distribution assumption, and a General model incorporating spatial variance
      abundance and occupancy-abundance relationships were fitted to data on adult M.
      ochroptera, Exosoma and Ootheca from western Kenya, southern Malawi and eastern
      Zambia. Very strong variance to abundance relationships were observed in the
      spatial pattern of all three beetles. The occupancy-abundance relationships were
      also positive and strong in all beetles. The occupancy and abundance predicted by
      the four models were closest to the observed at lower densities compared with
      higher beetle densities. At higher population densities, the NBD and the General
      model gave better fit for M. ochroptera and Exosoma. For Ootheca populations, the
      Poisson and NBD models gave better fit at higher population densities. The
      relationships established here can be used as guide to estimate beetle densities
      for decision-making in pest management.

PMID- 16441907
TI  - The effects of host physiology on the attraction of tsetse (Diptera: Glossinidae)
      and Stomoxys (Diptera: Muscidae) to cattle.
AB  - In Zimbabwe, studies were made of the numbers of tsetse (Glossina spp.) and
      stable flies (Stomoxys spp.) attracted to cattle of different nutritional status,
      age and sex. Host odours were analysed to determine the physiological basis of
      these differences and improved methods are described for measuring rates of
      production of kairomones. Seasonal fluctuations in host weight, related to
      changes in pasture quality, had no significant effect on attraction of tsetse or
      Stomoxys. However, both attraction to different individuals and carbon dioxide
      production by these individuals were strongly correlated with weight, suggesting
      a possible link. Attraction to the odour from different types of cattle decreased
      in the order ox>cow>heifer>calf, and oxen were twice as attractive as calves of
      less than 12 months old. Lactation did not alter the relative attractiveness of
      cows. Calves less than six months old produced lower levels of carbon dioxide,
      acetone, octenol and phenols than oxen, but for older calves and cows, levels of
      production of known kairomones and repellents were similar to those of an ox.
      Carbon dioxide produced by cattle varied according to time of day and the
      animal's weight; cattle weighing 500 kg produced carbon dioxide at a mean rate of
      2.0 l min(-1) in the morning and 2.8 l min(-1) in the afternoon compared to
      respective rates of 1.1 and 1.9 l min(-1) for cattle weighing 250 kg.
      Artificially adjusting the doses of carbon dioxide produced by individual cattle
      to make them equivalent did not remove significant differences in attractiveness
      for tsetse but did for Stomoxys. Increasing the dose of carbon dioxide from 1 to
      4 l min(-1) in a synthetic blend of identified kairomones simulating those
      produced by a single ox, increased attractiveness to tsetse but not to the level
      of an ox. The results suggest that the main sources of differences in the
      attractiveness of individual cattle are likely to be variation in the production
      of carbon dioxide and, for tsetse, other unidentified kairomone(s). The
      biological and practical implications of these findings are discussed.

PMID- 16441908
TI  - The effect of bait design on bait consumption in termites (Isoptera:
      Rhinotermitidae).
AB  - The efficacy of baiting as a pest control method relies on the bait appealing to
      the pest species. In the case of wood-eating termites, bait stations should be
      designed to encourage termite presence and to maximize their consumption of bait
      matrix in order to expedite control in minimal time. A field experiment examined
      the effect of bait size (one large bait or four small baits of equivalent total
      size, with commensurate inspection and replacement schedules), compaction
      (tightly rolled or loosely folded) and composition (paper only or paper plus
      wood) on termite presence and on untreated bait paper removal rates over four
      months. All three factors were significant, with bait size the most important
      factor, followed by compaction and then composition. The least effective baits
      were small, compacted (rolled) paper-only baits with monthly inspections; these
      had the highest abandonment rate (70%) and had the least paper removed (mean of
      24 g). The most effective baits were large, folded paper-plus-wood baits with
      inspections at two months; these had the lowest abandonment rate (20%) and had
      the highest paper removal (mean of 112 g). The more than four-fold difference
      between these baits types demonstrates that bait efficacy can be altered
      considerably merely by changing bait design without adding new ingredients to the
      bait matrix.

PMID- 16441909
TI  - Midgut proteases of the cardamom shoot and capsule borer Conogethes punctiferalis
      (Lepidoptera: Pyralidae) and their interaction with aprotinin.
AB  - Protease inhibitors cause mortality in a range of insects, and transgenic plants
      expressing protease inhibitors have been protected against pest attack,
      particularly internal feeders that are not amenable to control by conventional
      means. A study of luminal proteases in Conogethes punctiferalis Guenee was
      performed to identify potential targets for proteinaceous biopesticides, such as
      protease inhibitors. The midgut protease profile of the gut lumen from C.
      punctiferalis was studied to determine the conditions for optimal protein
      hydrolysis. Optimum conditions for peptidase activity were found to be in 50 mm
      Tris-HCl, pH 10 containing 20 mm CaCl2; incubation for 30 min at 40 degrees C.
      Four synthetic substrates, i.e. benzoyl-arg-p-nitroanilide, benzoyl-tyr-p
      nitroanilide, succinyl-ala-ala-pro-leu-p-nitroanilide (SAAPLpNA) and leu-p
      nitroanilide were hydrolysed by C. punctiferalis gut proteases in Tris-HCl buffer
      pH 10. Trypsin and elastase-like chymotrypsin were the prominent digestive
      proteases, and age-related modulation of midgut proteases existed for trypsin,
      chymotrypsin, elastase-like chymotrypsin and leucine aminopeptidase. Serine
      protease inhibitors such as aprotinin, soybean trypsin inhibitor and
      phenylmethanesulfonyl fluoride inhibited peptidase activity. Some metal ions such
      as Ca(2+), Mg(2+), Pb(2+) and Co(2+) enhanced BApNA-ase activity whereas others
      like Mn(2+), Zn(2+), Cu(2+), Fe(2+) and Hg(2+) were inhibitory at 6 mm
      concentration. Trypsin and elastase-like chymotrypsin were significantly
      inhibited by 94% and 29%, respectively, by aprotinin (150 nm) under in vitro
      conditions. A possible incorporation of protease inhibitors into transgenic
      plants is discussed.

PMID- 16441911
TI  - The ketogenic diet in children with epilepsy.
AB  - Children with epilepsy, especially those facing intractable seizures, experience
      a great impact on the quality of their lives. Effective treatment is essential,
      and although new anti-epileptic drugs have shown an improved profile of action,
      still a substantial number of children look for more efficacious ways of
      treatment that are far away from potential toxicity and ineffectiveness. The
      ketogenic diet is a dietary therapy for epileptic children based on manipulation
      of metabolism principles and brain energetics. This regimen aims to produce a
      controlled ketonaemia through excessive dietary fat intake, little carbohydrates
      and adequate (for growth) protein. The present paper is a review of previous and
      current papers regarding the proposed mechanisms of the ketogenic diet's action,
      and the efficacy of the regimen on epileptic children. Unfortunately, a few small
      studies in sample size and duration tried to evaluate the potential risks of this
      regimen and their results were rather inconclusive. Further research needs to be
      done in order for the exact mechanism of the ketogenic diet to be clarified which
      will help to improve the diet's application, especially for vulnerable epileptic
      children as far as their growth is concerned.

PMID- 16441912
TI  - Is reversal of endothelial dysfunction by tea related to flavonoid metabolism?
AB  - Dietary flavonoids can improve endothelial function, but the response varies
      between individuals. Wide variability is also seen in flavonoid O-methylation, a
      major pathway of flavonoid metabolism. The O-methylation of flavonoids could
      alter activity, and thus influence any effect on endothelial function. The
      objective of the current analysis was to investigate whether variability in the
      endothelial function response to ingestion of tea, a rich source of flavonoids,
      is related to the degree of O-methylation of flavonoids. This relationship was
      investigated in two studies in which endothelium-dependent flow-mediated
      dilatation (FMD) of the brachial artery was assessed and urinary 4-O-methylgallic
      acid (4OMGA) excretion was used as a marker of the O-methylation of tea-derived
      flavonoids. In the first study, amongst participants consuming five cups of tea
      per day for 4 weeks, the degree of increase in 4OMGA excretion was inversely
      associated with the change in FMD responses (r -078, P=0.008). In the second
      study, there was a significant difference in the FMD responses to acute ingestion
      of three cups of tea between individuals with a low (<median) and high (>median)
      4OMGA response (1.94 (sem 0.79) % and -0.25 (sem 0.53) %, respectively; P=0.03).
      That is, any improvement in FMD following ingestion of tea may be enhanced in
      individuals who O-methylate less of the absorbed flavonoids. The present results
      are consistent with the suggestion that differences in flavonoid metabolism may
      influence their effect on endothelial function. Thus, differences in flavonoid
      metabolism could be related to the level of benefit of dietary flavonoids on the
      risk of CVD.

PMID- 16441913
TI  - Docosahexaenoic acid enhances the antioxidant response of human fibroblasts by
      upregulating gamma-glutamyl-cysteinyl ligase and glutathione reductase.
AB  - The chemopreventive effects of dietary n-3 PUFA in various pathologies has so far
      remained controversial, and we were interested in studying their potential
      influence on cell redox status. DHA (22 : 6n-3), a typical highly unsaturated n-3
      PUFA, was used at 30 micromol/l in a model of human fibroblast cell culture. A
      dose-response effect, roughly linear, was checked for DHA between 0 and 60
      micromol/l, and was accompanied by a large increase in intracellular GSH content.
      A time course study of this effect shows that, after a short fall, as soon as 4 h
      after the beginning of the experiment, the large increase in the GSH content was
      associated with elevated catalytic activities of gamma-glutamyl-cysteinyl ligase,
      glutathione reductase and glutathione S-transferase. This coordinated response is
      characteristic of an antioxidant response and was confirmed by the induction of
      expression of mRNA for gamma-glutamyl-cysteinyl ligase, glutathione reductase and
      haem-oxygenase. This large increase in the GSH content contributes to decreasing
      the reactive oxygen species level, as assessed by the decreased accumulation of
      dichlorofluorescein inside cells. To our knowledge, this is the first report on a
      specific and potent effect of DHA for decreasing the oxidative stress of human
      fibroblasts.

PMID- 16441914
TI  - Fat and protein metabolism in growing steers fed either grass silage or dried
      grass.
AB  - Cattle fed grass silage diets have been reported to have high carcass fat:protein
      ratios. The effect of grass silage and dried grass diets, fed at different levels
      of intake to ensure a range of equivalent metabolisable energy intakes (MEI) from
      1 .1 x metabolisable energy requirement for maintenance to ad libitum, on fat and
      protein metabolism in twenty-four Hereford x Friesian steers was investigated.
      After about 84 d of dietary treatment rates of whole-body fat and protein
      metabolism were measured, as were rates of lipogenesis in omental, perirenal and
      subcutaneous adipose tissue. Carcass composition was determined. Animals fed
      silage had greater (P<0 .001) carcass fat:protein ratios than animals fed dried
      grass at equivalent levels of MEI. Animals fed silage had lower (P<0 .001) rates
      of protein gain. Rates of leucine entry and oxidation were lower (P<0 .001) in
      animals fed silage, but there was no dietary difference in the rate of whole-body
      protein synthesis. There was no dietary difference in the rate of carcass fat
      gain, but rates of lipogenesis in perirenal adipose tissue were significantly
      (P=0 .007) higher in animals fed silage. There was no dietary difference in the
      rate of palmitate and glycerol entry or palmitate oxidation. There were no
      interactions between MEI and diet, indicating that increments of energy were
      utilised with the same efficiency from both diets. It was concluded that the high
      carcass fat:protein ratios of young growing steers was due to limited rates of
      protein accretion and not to elevated rates of carcass fat accretion.

PMID- 16441916
TI  - Absorption, tissue distribution and excretion of pelargonidin and its metabolites
      following oral administration to rats.
AB  - Recent reports have demonstrated various cardiovascular and neurological benefits
      associated with the consumption of foods rich in anthocyanidins. However,
      information regarding absorption, metabolism, and especially, tissue distribution
      are only beginning to accumulate. In the present study, we investigated the
      occurrence and the kinetics of various circulating pelargonidin metabolites, and
      we aimed at providing initial information with regard to tissue distribution.
      Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and
      present in plasma following oral gavage to rats. In addition, the main
      structurally related pelargonidin metabolite identified in plasma and urine was
      pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission
      product of pelargonidin, was detected in plasma and urine samples obtained at 2
      and 18 h after ingestion. At 2 h post-gavage, pelargonidin glucuronide was the
      major metabolite detected in kidney and liver, with levels reaching 0.5 and 0.15
      nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues
      contained detectable levels of the aglycone, with the glucuronide also present in
      the lungs. Other tissues, including spleen and heart, did not contain detectable
      levels of pelargonidin or ensuing metabolites. At 18 h post-gavage, tissue
      analyses did not reveal detectable levels of the aglycone nor of pelargonidin
      glucuronides. Taken together, our results demonstrate that the overall uptake of
      the administered pelargonidin was 18 % after 2 h, with the majority of the
      detected levels located in the stomach. However, the amounts recovered dropped to
      1.2 % only 18 h post-gavage, with the urine and faecal content constituting
      almost 90 % of the total recovered pelargonidin.

PMID- 16441917
TI  - Evidence of negative energy balance using doubly labelled water in elite Kenyan
      endurance runners prior to competition.
AB  - Previous studies have found Kenyan endurance runners to be in negative energy
      balance during training and prior to competition. The aim of the present study
      was to assess energy balance in nine elite Kenyan endurance runners during heavy
      training. Energy intake and expenditure were determined over 7 d using weighed
      dietary intake and doubly labelled water, respectively. Athletes were on average
      in negative energy balance (mean energy intake 13 241 (SD 1330) kJ/d v. mean
      energy expenditure 14 611 (SD 1043) kJ/d; P=0.046), although there was no loss in
      body mass (mean 56.0 (SD 3.4) kg v. 55.7 (SD 3.6) kg; P=0.285). The calculation
      of underreporting was 13 % (range -24 to +9 %) and almost entirely accounted for
      by undereating (9 % (range -55 to +39 %)) as opposed to a lack of significant
      underrecording (i.e. total water intake was no different from water loss (mean
      4.2 (SD 0.6) l/d v. 4.5 (SD 0.8) l/d; P=0.496)). Fluid intake was modest and
      consisted mainly of water (0.9 (SD 0.5) l/d) and milky tea (0.9 (SD 0.3) l/d).
      The diet was high in carbohydrate (67.3 (SD 7.8) %) and sufficient in protein
      (15.3 (SD 4.0) %) and fat (17.4 (SD 3.9) %). These results confirm previous
      observations that Kenyan runners are in negative energy balance during periods of
      intense training. A negative energy balance would result in a reduction in body
      mass, which, when combined with a high carbohydrate diet, would have the
      potential in the short term to enhance endurance running performance by reducing
      the energy cost of running.

PMID- 16441915
TI  - Effect of isomalt consumption on faecal microflora and colonic metabolism in
      healthy volunteers.
AB  - Due to its low digestibility in the small intestine, a major fraction of the
      polyol isomalt reaches the colon. However, little is known about effects on the
      intestinal microflora. During two 4-week periods in a double-blind, placebo
      controlled, cross-over design, nineteen healthy volunteers consumed a controlled
      basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were
      collected at the end of each test phase and various microbiological and luminal
      markers were analysed. Fermentation characteristics of isomalt were also
      investigated in vitro. Microbiological analyses of faecal samples indicated a
      shift of the gut flora towards an increase of bifidobacteria following
      consumption of the isomalt diet compared with the sucrose diet (P<0.05). During
      the isomalt phase, the activity of bacterial beta-glucosidase decreased (P<0.05)
      whereas beta-glucuronidase, sulfatase, nitroreductase and urease remained
      unchanged. Faecal polyamines were not different between test periods with the
      exception of cadaverine, which showed a trend towards a lower concentration
      following isomalt (P=0.055). Faecal SCFA, lactate, bile acids, neutral sterols,
      N, NH3, phenol and p-cresol were not affected by isomalt consumption. In vitro,
      isomalt was metabolized in several bifidobacteria strains and yielded high
      butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low
      energy sweetener, has to be considered a prebiotic carbohydrate that might
      contribute to a healthy luminal environment of the colonic mucosa.

PMID- 16441918
TI  - L-Arginine attenuates xanthine oxidase and myeloperoxidase activities in hearts
      of rats during exhaustive exercise.
AB  - The present study was to investigate the effects of l-arginine (l-Arg)
      supplementation on cardiac oxidative stress and the inflammatory response in rats
      following acute exhaustive exercise on a treadmill. Rats were randomly divided
      into four groups: sedentary control (SC); SC with l-Arg treatment (SC+Arg);
      exhaustive exercise (E); exhaustive exercise with l-Arg treatment (E+Arg). Rats
      in groups SC+Arg and E+Arg received a 2 % l-Arg diet. Rats in groups E and E+Arg
      performed an exhaustive running test on a treadmill at a final speed of 30 m/min,
      10 % grade, at approximately 70-75 % VO2max. The results showed a significant
      increase in cardiac xanthine oxidase (XO) and myeloperoxidase activities and
      membrane lipid peroxidation endproduct (malondialdehyde; MDA) levels of exercised
      rats compared with SC rats. The increased cardiac XO activity and MDA levels in
      exercised rats were significantly decreased in exercised rats supplemented with l
      Arg. Myocardial GSSG content increased whereas the GSH:GSSG ratio was depressed
      in exercised rats compared with SC rats. Cardiac GSSG levels significantly
      decreased, whereas total glutathione, GSH and the GSH:GSSG ratio increased in
      exercised rats supplemented with l-Arg compared with exercised rats. The
      activities of creatinine kinase (CK) and lactate dehydrogenase (LDH), and
      lactate, uric acid, and nitrite and nitrate levels in the plasma significantly
      increased in exercised rats compared with SC rats. The activities of plasma CK
      and LDH were significantly decreased in l-Arg-supplemented plus exercised rats
      compared with exercised rats. These findings suggest that l-Arg supplementation
      reduces the oxidative damage and inflammatory response on the myocardium caused
      by exhaustive exercise in rats.

PMID- 16441920
TI  - A comparison of the effect of forage type and level of feeding on the
      digestibility and gastrointestinal mean retention time of dry forages given to
      cattle, sheep, ponies and donkeys.
AB  - Four cattle, sheep, ponies and donkeys were fed dehydrated lucerne, early-cut
      hay, later-cut hay or barley straw in a Latin square-based design for four
      periods of 35 d. In the first sub-period animals were fed the diets ad libitum (1
      21 d) and in the second sub-period they were fed the same diet restricted to 0.75
      of ad libitum intake (days 22-35). Measurements of forage intake, apparent
      digestibilities and gastrointestinal mean retention times (MRT) were made in the
      last 7 d of each sub-period. Differences between species in voluntary DM intake
      (VDMI; g/kg live weight (LW)(0.75) and g/LW) were greatest on the lucerne and
      least on barley straw. Cattle VDMI (g/kg LW(0.75)) compared with intake of the
      other species was > ponies > sheep > donkeys on lucerne. On barley straw VDMI
      (g/kg LW(0.75)) of cattle compared with intake of the other species was = donkey
      = ponies > sheep. VDMI of hays were intermediate between the lucerne and straw
      forages. Apparent digestibilities of DM, organic matter (OM), neutral-detergent
      fibre (NDF) and acid-detergent fibre (ADF) of the lucerne and hays were higher in
      the ruminants than in the equids. Effect of feeding level was not significant.
      Gastrointestinal MRT was shorter in the equids than in the ruminants. On straw
      diets donkeys showed similar apparent digestibilities of feed components to those
      of the cattle, whilst apparent digestibility of the straw diet by the ponies was
      lowest. Results are discussed in relation to evolutionary differences in feeding
      and digestion strategy associated with fore- or hind-gut fermentation in
      ruminants and equids.

PMID- 16441919
TI  - Effect of DHA supplementation on digestible starch utilization by rainbow trout.
AB  - Rainbow trout has a limited ability to utilize digestible carbohydrates
      efficiently. Trout feeds generally contain high levels of DHA, a fatty acid known
      to inhibit a number of glycolytic and lipogenic enzymes in animals. A study was
      conducted to determine whether carbohydrate utilization by rainbow trout might be
      affected by dietary DHA level. Two low-carbohydrate (<4 % digestible
      carbohydrate) basal diets were formulated to contain 1 (adequate) or 4 (excess)
      g/100 g DHA diet respectively. The two basal diets were diluted with increasing
      levels of digestible starch (0 %, 10 %, 20 % and 30 %, respectively) to produce
      eight diets. These diets were fed to fish for 12 weeks at 15 degrees C according
      to a pair-fed protocol that consisted of feeding the same amount of basal diet
      but different amounts of starch. Live weight, N and lipid gains, hepatic glycogen
      and plasma glucose values significantly increased, whereas feed efficiency
      (gain:feed) significantly decreased, with increasing starch intake (P<0.05). The
      retention efficiency of N (N gain/digestible N intake) improved with starch
      supplementation but was not affected by DHA level (P>0.05). Starch increased the
      activity of glucokinase, pyruvate kinase, glucose 6-phosphate dehydrogenase and
      fatty acid synthase (P<0.05) but did not affect hexokinase and malic enzyme
      activity. DHA had no effect on growth but increased plasma glucose and reduced
      carcass lipid and liver glycogen contents (P<0.05). Glycolytic and lipogenic
      enzymes were not affected by DHA level, except for pyruvate kinase, which was
      reduced by increasing DHA level. These results suggest only a marginal effect of
      dietary DHA on the ability of fish to utilize carbohydrate.

PMID- 16441921
TI  - Effects of defaunation on fermentation characteristics and biotin balance in an
      artificial rumen-simulation system (RUSITEC) receiving diets with different
      amounts and types of cereal.
AB  - Biotin is required by rumen microbes for efficient fermentation. To evaluate the
      role of protozoa in ruminal biotin metabolism, five diets composed of grass hay
      or of grass hay/cereal grain mixtures were supplied to faunated or defaunated
      RUSITEC fermenters. In the mixed diets, hay was replaced to 33:67 or 67:33 w/w on
      an air-dried basis by either wheat or maize grain in order to simulate different
      cellulolytic and amylolytic fermentation conditions. Defaunation increased SCFA
      production, whereas NH4 concentration and the release of CH4 were reduced. Biotin
      input declined when cereal grain was used to replace the hay. With the exception
      of the high-wheat treatment, defaunated fermenters yielded higher biotin outputs
      than faunated fermenters. The biotin balance, calculated as the difference
      between the total biotin output (biotin in the solid residue contained in the
      nylon bags after fermentation plus the biotin in the effluent) and the biotin
      input with the feed, was negative for all the dietary treatments apart from
      fermenters supplied with the high-maize diet. It was less negative or, in the
      case of the high-maize diets, more positive for defaunated compared with faunated
      fermenters. It was concluded that, under normal faunated conditions, protozoa
      directly utilise or indirectly affect the bacterial synthesis and/or utilisation
      of biotin. With diets of a high fermentation potential, as realised with the high
      wheat diet, protozoa prevent the development of a bacterial population that would
      utilise high or synthesise low amounts of biotin.

PMID- 16441922
TI  - Binding and the effect of the red kidney bean lectin, phytohaemagglutinin, in the
      gastrointestinal tract of suckling rats.
AB  - Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to
      induce growth and precocious functional maturation of the gastrointestinal tract.
      The aim of the present study was to explore the mechanism of this action.
      Suckling rats, 14 d old, were fed a single dose of PHA (0.05 mg/g body weight) or
      saline. The binding of PHA to the gut epithelium and its effect on the morphology
      and functional properties of the gut and pancreas were studied up to 3 d after
      treatment. Initially, at 1-24 h, the PHA bound along the gut mucosal lining,
      resulting in disturbed gut morphology with villi shortening and rapid decreases
      in disaccharidase activities and macromolecular absorption capacity. During a
      later phase, between 1 and 3 d, the PHA binding had declined, and an uptake by
      enterocytes was observed. An increase in crypt cell proliferation and gut growth
      became evident during this period, together with a functional maturation, as
      indicated by increases in disaccharidase (maltase and sucrase) activities and the
      low macromolecular absorption capacity. Pancreas growth also increased, as did
      its content of digestive enzymes. We conclude that enteral exposure to PHA in
      suckling rats temporarily causes mucosal disarrangement and functional impediment
      of the gut, which may be explained by binding to and disruption of the gut mucosa
      and a two-fold increase in the plasma corticosterone concentration. These
      findings may lead to a better understanding of the role of diet in
      gastrointestinal maturation and may constitute a basis for the treatment of
      mammals having an immature gut.

PMID- 16441923
TI  - Influence of the Phaseolus vulgaris phaseolin level of incorporation, type and
      thermal treatment on gut characteristics in rats.
AB  - Phaseolus vulgaris phaseolin has been shown to stimulate faecal losses of
      endogenous N in rats. Experiments with purified phaseolin were carried out in
      rats to test the hypothesis that these losses reflect intestinal disorders.
      Phaseolin composition varies depending on its constitutive subunits. Therefore,
      three phaseolin types (S, T, I) were tested. Phaseolin T was incorporated in
      varying levels (0, 33, 67 or 100 % of the dietary protein) as raw material in
      experiment 1. In experiment 2, the three phaseolin types were incorporated at 50
      %, with or without previous thermic treatment. Raw casein was the basal protein
      source and was also heated in experiment 2. Faecal digestibility of phaseolin and
      gut integrity were evaluated in both experiments. The incorporation level or type
      of phaseolin had little effect on gross anatomy of gut segments but these factors
      influenced the weight and pH of fresh contents of the stomach and caecum
      (P<0.05). Raw phaseolin T incorporated at various levels led to an enlargement of
      duodenal villi together with a tendency for increased crypt depth in the jejunum
      (P=0.06). Activities of both alkaline phosphatase in the duodenum and
      aminopeptidase N in the ileum decreased (P<0.05) after thermal treatment of
      casein while they increased (P<0.05) for heat-treated phaseolin S and T,
      respectively. In conclusion, raw phaseolin had no effect on the tissue weight of
      gut segments and induced limited alterations in the small intestine. Differences
      due to phaseolin level or type were limited too.

PMID- 16441924
TI  - Fish-bone peptide increases calcium solubility and bioavailability in
      ovariectomised rats.
AB  - Fish-bone peptides (FBP) with a high affinity to Ca were isolated using
      hydroxyapatite affinity chromatography, and FBP II with a high ratio of
      phosphopeptide was fractionated in the range of molecular weight 5.0-1.0 kDa by
      ultramembrane filtration. In vitro study elucidated that FBP II could inhibit the
      formation of insoluble Ca salts in neutral pH. In vivo effects of FBP II on Ca
      bioavailability were further examined in the ovariectomised rat. During the
      experimental period, Ca retention was increased and loss of bone mineral was
      decreased by FBP II supplementation in ovariectomised rats. After the low-Ca
      diet, the FBP II diet, including both normal level of Ca and vitamin D,
      significantly decreased Ca loss in faeces and increased Ca retention compared
      with the control diet. The levels of femoral total Ca, bone mineral density, and
      strength were also significantly increased by the FBP II diet to levels similar
      to those of the casein phosphopeptide diet group (no difference; P>0.05). In the
      present study, the results proved the beneficial effects of fish-meal in
      preventing Ca deficiency due to increased Ca bioavailability by FBP intake.

PMID- 16441925
TI  - Taiwanese vegetarians have higher insulin sensitivity than omnivores.
AB  - The present study was designed to examine the effects of habitual consumption of
      Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic
      control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan
      (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were
      omnivores. Dietary intakes were measured, and blood levels of nutrients and
      hormones were analysed. Vegetarians consumed less energy, fat and protein, but
      more fibre than the omnivores. Compared with the omnivores, the vegetarians had,
      on average, lower BMI and smaller waist circumference. Except for slightly lower
      levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed
      similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone,
      T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had
      significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and
      plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance,
      as calculated by the homeostasis model assessment method, was significantly lower
      in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell
      function was not different between the two groups. BMI and diet were both
      independent predictors for insulin resistance, and contributed 18 and 15 % of the
      variation in insulin resistance, respectively. In conclusion, Taiwanese
      vegetarians had lower glucose and insulin levels and higher insulin sensitivity
      than did the omnivores. Diet and lower BMI were partially responsible for the
      high insulin sensitivity observed in young Taiwanese vegetarians.

PMID- 16441926
TI  - Effect of dietary supplementation with beta-casein A1 or A2 on markers of disease
      development in individuals at high risk of cardiovascular disease.
AB  - The present study is the first to examine the hypothesis that dietary
      supplementation with beta-casein A1 promotes an increased risk relative to
      supplementation with beta-casein A2 in patients traditionally at high risk of
      developing CVD. The study was conducted in fifteen asymptomatic participants (six
      male; nine female) at high risk of developing CVD. A double-blind cross-over
      study design was used with a total duration of 24 weeks. Dietary intervention was
      a daily supplementation (25 g) of either casein A1 or A2 (for 12 weeks each).
      Surrogate measures of cardioprotection studied included the examination of
      vascular (endothelium and arterial) function, resting blood pressure, plasma
      lipids and biochemical markers of inflammation. Total plasma cholesterol levels
      were significantly lower following 12 weeks of both casein A1 and A2
      interventions but the decrease was not different between intervention. Plasma
      insulin, homocysteine, C-reactive protein, fibrinogen, protein C and S and von
      Willebrand factor levels were not different between the two casein supplements.
      Endothelium function, measured as a vascular response using venous occlusion
      plethysmography to intra-arterial infusions of the endothelium-dependent agonist
      acetylcholine, were not different between the two casein interventions.
      Similarly, neither blood pressure nor measures of large artery stiffness were
      affected by differing the casein variant. We therefore conclude that there is no
      evidence from the present study that supplementation with casein A1 has any
      cardiovascular health disadvantage over consumption of casein A2.

PMID- 16441927
TI  - Postprandial serum folic acid response to multiple doses of folic acid in
      fortified bread.
AB  - The benefit of the introduction of mandatory folic acid fortification of all
      flour products in the USA in 1998 has been amply demonstrated in a reduction of
      neural tube defect births. Doubt has been cast on the actual level of
      fortification and recent calculations have shown that the level of folic acid
      fortification is likely to have been over twice the amount mandated. The
      implication of this is that a greater proportion of the population are likely to
      have consumed folic acid at >1 mg/d, the Food and Drug Administration safe upper
      level of intake. Using the criteria of appearance of synthetic folic acid in
      serum, the objective of this pilot study was to investigate the consequences of
      consumption of baked bread preparations containing 1 mg folic acid. Four healthy
      adult volunteers undertook each dosing schedule 2 weeks apart. This consisted of
      a single dose of 1000 microg, two doses of 500 microg, three doses of 333 microg,
      five doses of 200 microg and, finally, ten doses of 100 microg. Serum was
      collected pre- and postprandially and analysed for synthetic folic acid by a
      combined HPLC-microbiological assay for folic acid. Folic acid appeared in all
      subjects at all test doses, with the effect more pronounced as the standard dose
      was administered in smaller amounts over the test period. Approaches to optimise
      folic acid intake in target populations as part of a universal fortification
      strategy should take into consideration the potential hazard of over-exposure in
      groups consuming high amounts of flour-based products.

PMID- 16441928
TI  - Intradialytic parenteral nutrition: comparison of olive oil versus soybean oil
      based lipid emulsions.
AB  - Lipid, oxidative and inflammatory parameters are frequently altered in dialysis
      patients and may be worsened by intravenous lipid emulsions (ILE). We assessed
      the efficacy and tolerance of olive as compared with standard soybean oil-based
      ILE during intradialytic parenteral nutrition (IDPN). IDPN mixtures containing
      amino acids, glucose, and either olive oil (OO group, n 17) or soybean oil-based
      ILE (SO group, n 18) were administered in a 5-week randomized, double-blind
      study. On days 0 and 35, patients' nutritional status was assessed by BMI,
      normalized protein catabolic rate, predialytic creatinine, serum albumin and
      transthyretin; lipid metabolism by plasma LDL- and HDL-cholesterol,
      triacylglycerols, phospholipids, apo A-I, A-II, B, C-II, C-III, E and lipoprotein
      (a); oxidative status by alpha-tocopherol, retinol, selenium, glutathione
      peroxidase, malondialdehyde and advanced oxidized protein products; inflammatory
      status by serum C-reactive protein, orosomucoid, IL-2 and IL-6. No serious
      adverse event was observed. Significant changes were observed from day 0 to day
      35 (P<0.05): nutritional criteria improved (albumin in OO; albumin, transthyretin
      and creatinine in SO); LDL-cholesterol, apo B, C-II, C-III and apo A-I/A-II ratio
      increased in both groups. HDL-cholesterol decreased in OO; apo E increased and
      lipoprotein (a) decreased in SO; alpha-tocopherol/cholesterol ratio increased in
      OO; malondialdehyde decreased in both groups; IL-2 increased in both groups. The
      between-group comparison only showed the following differences: alpha
      tocopherol/cholesterol increased in OO; lipoprotein (a) decreased in SO. From
      these data, it was concluded that OO- and SO-based IDPNs similarly improved
      nutritional status and influenced plasma lipid, oxidative, inflammatory and
      immune parameters.

PMID- 16441929
TI  - Nutrient-stimulated glucagon-like peptide 1 release after body-weight loss and
      weight maintenance in human subjects.
AB  - Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released in response
      to nutrient ingestion. Postprandial GLP-1 release has been reported to be
      attenuated in obese subjects, but reports on the effect of weight loss on GLP-1
      are conflicting. The aim of the present study was to clarify the effect of a
      weight-loss period and a consecutive weight-maintenance period on nutrient
      stimulated GLP-1 release in obese subjects. Nutrient-stimulated (standard
      breakfast; 1.9 MJ) GLP-1 release was investigated in thirty-two obese subjects on
      three occasions: before weight loss (T1) (BMI 30.0 (sd 2.5) kg/m(2)); after a 6
      week very-low-energy diet (VLED) (T2) (BMI 27.6 (sd 2.3) kg/m(2)); after a 3
      month weight-maintenance period (T3) (BMI 27.9 (sd 2.3) kg/m(2)). At each
      occasion, following a fasting blood sample the test meal was fed and blood was
      drawn every 30 min for 2 h relative to ingestion in order to determine plasma GLP
      1, insulin, glucose and NEFA concentrations. Subjects lost 7 (sd 3.4) kg during
      the VLED (P<0.0001) and regained 1 (sd 3.2) kg during the weight-maintenance
      period (NS). The area under the curve for nutrient-stimulated plasma GLP-1
      (pmol/l x h) was significantly decreased (P=0.01) at T2 (6.8 (sd 1)) compared
      with T1 (12.8 (sd 2.9)) and T3 (11.1 (sd 1.5)). Since we found a rebound of
      concentrations after a weight-maintenance period, decrease after weight loss
      seems to be transient and possibly due to a negative energy balance.

PMID- 16441930
TI  - Fatty acid composition of skeletal muscle and adipose tissue in Spanish infants
      and children.
AB  - There is a relationship between the fatty acid profile in skeletal muscle
      phospholipids and peripheral resistance to insulin in adults, but similar data
      have not been reported in infancy and childhood. The objective of this study was
      to investigate the fatty acid composition of skeletal muscle and adipose tissue
      across the paediatric age range. The fatty acid profile of skeletal muscle
      phospholipids and adipose tissue triacylglycerols was analysed in ninety-three
      healthy Spanish infants and children distributed into four groups: group 1 (0 to
      <2 years, n 10); group 2 (2 to <5 years, n 41); group 3 (5 to <10 years, n 24);
      group 4 (10 to 15 years, n 18). In skeletal muscle phospholipids, oleic acid (18:
      1n-9cis) content decreased significantly whereas that of linoleic (18: 2n-6) acid
      increased significantly with age (P for trend <0.01). In adipose tissue, the
      contents of triacylglycerol and linoleic acid increased significantly across the
      paediatric age range (P for trend <0.01), whereas dihomo-gamma-linolenic (20: 3n
      6) and arachidonic (20: 4n-6) showed significant differences between groups. The
      variations in fatty acid composition observed with age indicated an imbalance in
      dietary n-3/n-6 long-chain PUFA.

PMID- 16441931
TI  - Processing of complementary food does not increase hair zinc levels and growth of
      infants in Kilosa district, rural Tanzania.
AB  - A community-based, randomized, placebo-controlled, double-blind trial was
      conducted from March 2001 to March 2002 in Kilosa, a rural district of Morogoro
      Region in Tanzania. One hundred and fifty-eight infants were selected randomly
      from lists of local Maternal and Child Health Care Centres and received either
      processed complementary food (PCF) or unprocessed complementary food (UPCF) from
      age 6 to 12 months. Processing increased Zn solubility and energy density of the
      porridge prepared from the complementary food (CF) as determined in vitro.
      Phytate:Zn molar ratio of the PCF and UPCF was 25.8 and 47.5, respectively. Under
      the study conditions, the processing of CF did not improve Zn status as measured
      by hair analysis. No significant correlations were found between hair Zn values
      and anthropometric measurements. Our findings suggest that processing alone of
      cereal-based CF may be insufficient to ensure an adequate supply of Zn to improve
      growth and Zn status of infants. Dietary modification to tackle Zn deficiencies
      in similar target groups may therefore only be successful when other Zn-rich
      foods such as meat and fish are included.

PMID- 16441932
TI  - Folate absorption from folate-fortified and processed foods using a human
      ileostomy model.
AB  - Data on folate absorption from food from validated human studies using
      physiological folate doses are still needed to estimate dietary requirements and
      to formulate recommendations. The aim of the present work was to study the
      effects from fortified and processed foods on folate absorption in ileostomy
      volunteers (n 9) using the area under the plasma concentration curve (AUC) and
      kinetic modelling. Using a standardized single-dose protocol, dairy products
      fortified with a candidate fortificant (6S)-5-methyltetrahydrofolate ((6S)-5-CH3
      H4folate), folic acid-fortified bread and a dessert creme containing natural
      yeast folate polyglutamates were compared with folate supplements. Absorbed
      folate was estimated by AUC and a kinetic model, and non-absorbed folate by
      ileostomal folate excretion. Median apparent absorption from test foods ranged
      from 55 to 86 %. Added folate-binding proteins (FBP) significantly reduced folate
      absorption from dairy products, as in the absence of FBP, AUC-dose-corrected
      ratios were increased and ileal folate excretion decreased. After in vivo
      gastrointestinal passage of dairy products containing FBP, up to 43 % of the
      ingested FBP was found in ileostomal effluent. Folate absorption was similar for
      (6S)-5-CH3-H4folate fortificant from fermented milk and for folic acid from
      fortified bread. Folic acid, ingested as food fortificant in bread, was
      significantly less absorbed compared with an isolated supplement. We conclude
      that all tested foods were suitable matrices for folate fortification. However,
      dairy products, fortified with the new candidate fortificant (6S)-5-CH3-H4folate,
      are suitable if no active FBP is present.

PMID- 16441933
TI  - Relationship between nutritional habits adopted by ulcerative colitis relevant to
      cancer development patients at clinical remission stages and molecular-genetic
      parameters.
AB  - UC (ulcerative colitis) patients have an increased risk of developing colorectal
      cancer compared with the normal population. The cause underlying this higher risk
      is not fully defined but includes nutritional and environmental factors
      concomitant with genetic alterations. We aimed to evaluate genetic stability in
      the colonic tissue of UC patients in clinical remission compared with the healthy
      population, and to establish a possible correlation between nutritional habits
      and these molecular assessments. UC patients (n 42) and healthy controls (n 37)
      participated in the study. All participants were histopathologically and
      medically diagnosed. Participants completed five separate 7 d dietary records,
      food-frequency questionnaires and validated 24 h recalls for nutritional
      assessment. The extent of chromosome 17 loss and the calculated chromosome index
      was determined in colon tissue biopsies by fluorescence in situ hybridisation.
      Correlations between the molecular and nutritional assessments were performed
      using Pearson's correlation coefficients. Significant differences in the
      nutritional intake of total fat (65 (SD 15) v. 89 (SD 25) g), cholesterol (330
      (SD 168) v. 464 (SD 177) mg), dietary fibre (32 (SD 4.7) v. 9 (SD 4) g), vitamin
      A (1009 (SD 209) v. 506 (SD 204) microg), vitamin C (308 (SD 108) v. 72 (SD 53)
      mg) and folic acid (412 (SD 89 microg) v. 187 (SD 107)) were recorded for UC
      patients compared with controls. Significant correlations were found for the
      consumption of different food groups and the chromosome index for chromosome 17.
      The results of our study suggest that the nutritional habits adopted by UC
      patients during clinical remission may affect key cellular components of the
      colonic tissue, inducing a high degree of aneuploidy and genetic instability, and
      probably affecting the development of colon cancer.

PMID- 16441934
TI  - Goitre and iodine deficiency in Afghanistan: a case-control study.
AB  - I deficiency is the leading cause of preventable mental retardation. A number of
      surveys in Afghanistan show goitre prevalence rates more than 20 % amongst
      children and women. Access to iodised salt remains low, with disparate coverage
      by region, despite the recent implementation of a national salt iodisation
      programme. The objectives were to identify whether the presence of goitre is a
      satisfactory marker of I deficiency and to examine the relationship between
      goitre and thyroid function. A case-control study was carried out in children and
      women of childbearing age, stratified on the presence of goitre. Adequate levels
      of urinary I were observed in 6.8 % of all the subjects, and amongst the subjects
      without goitre, this figure was only 9 %. The presence of goitre was
      significantly associated with severe urinary I deficiency; however, the
      difference between the cases and controls was not as great as expected. An
      association between the presence of goitre and elevated thyroid-stimulating
      hormone (TSH) levels was observed, but 14 % of the children without palpable
      goitre also showed abnormal TSH levels.Given that the majority of subjects showed
      some degree of I deficiency and that children without goitre may have elevated
      TSH levels, the absence of goitre is an insufficient indicator to determine
      adequate I status. The risk of subsequent development of goitre, in the currently
      non-goitre population, is elevated. This suggests that short-term I
      supplementation should be considered independently of the presence of goitre or
      urinary I level, until the access to and consumption of iodised salt is
      generalised.

PMID- 16441935
TI  - A newly constructed and validated isoflavone database for the assessment of total
      genistein and daidzein intake.
AB  - The principal phyto-oestrogens (PO) in food are isoflavones, lignans, coumestans
      and prenylated flavonoids, with isoflavones and lignans being the most commonly
      found in UK diets. Until recently obtaining accurate data on the PO content of
      foods was hampered by lack of suitable analytical methods and validation
      techniques. Furthermore, although PO data exist for some foods, these foods may
      not be available in the UK. The aim of the present study was to construct a new,
      comprehensive isoflavone (total genistein + daidzein) database. Using data,
      mainly from recent GC-MS analysis, for approximately 300 foods available in the
      UK, and extensive recipe calculations, a new database was constructed containing
      approximately 6000 foods allocated an isoflavone value. By analysing 7 d weighed
      food diaries, the database was subsequently used to estimate isoflavone intake in
      two groups of healthy volunteers, omnivores (n 9) and vegetarians (n 10). Mean
      isoflavone intake in the vegetarian and omnivorous group was 7.4 (sem 3.05) and
      1.2 (sem 0.43) mg/d, respectively. Mean intake for the total group was 4.5 (sem
      1.89) mg/d. Main food sources of isoflavones for the vegetarian group were soya
      milk (plain), meat-substitute foods containing textured vegetable protein and
      soya protein isolate, soya mince, wholemeal bread and rolls, white bread and
      rolls, croissants and pitta breads, beans, raisins and soya sauce. Main food
      sources of isoflavones for the omnivorous group were soya yogurts, wholemeal
      bread and rolls, white bread and rolls, garlic bread, nan bread and brown bread,
      sultanas and scones.

PMID- 16441938
TI  - The ancestral human diet: what was it and should it be a paradigm for
      contemporary nutrition?
AB  - Awareness of the ancestral human diet might advance traditional nutrition
      science. The human genome has hardly changed since the emergence of behaviourally
      modern humans in East Africa 100-50 x 10(3) years ago; genetically, man remains
      adapted for the foods consumed then. The best available estimates suggest that
      those ancestors obtained about 35% of their dietary energy from fats, 35% from
      carbohydrates and 30% from protein. Saturated fats contributed approximately 7.5%
      total energy and harmful trans-fatty acids contributed negligible amounts.
      Polyunsaturated fat intake was high, with n-6:n-3 approaching 2:1 (v. 10:1
      today). Cholesterol consumption was substantial, perhaps 480 mg/d. Carbohydrate
      came from uncultivated fruits and vegetables, approximately 50% energy intake as
      compared with the present level of 16% energy intake for Americans. High fruit
      and vegetable intake and minimal grain and dairy consumption made ancestral diets
      base-yielding, unlike today's acid-producing pattern. Honey comprised 2-3% energy
      intake as compared with the 15% added sugars contribute currently. Fibre
      consumption was high, perhaps 100 g/d, but phytate content was minimal. Vitamin,
      mineral and (probably) phytochemical intake was typically 1.5 to eight times that
      of today except for that of Na, generally <1000 mg/d, i.e. much less than that of
      K. The field of nutrition science suffers from the absence of a unifying
      hypothesis on which to build a dietary strategy for prevention; there is no
      Kuhnian paradigm, which some researchers believe to be a prerequisite for
      progress in any scientific discipline. An understanding of human evolutionary
      experience and its relevance to contemporary nutritional requirements may address
      this critical deficiency.

PMID- 16441939
TI  - Achieving the goal of halving global hunger by 2015.
AB  - The FAO World Food Summit (WFS) in 1996 set the goal of halving the numbers of
      the global population suffering hunger by the year 2015, which was later
      incorporated into the UN Millennium Development Goals (MDG) that commit the
      international community to an expanded vision of development, and one that
      vigorously promotes human development as the key to sustaining social and
      economic progress in all countries. The two targets under the first MDG goal to
      eradicate poverty and hunger call for halving the proportion of individuals who
      suffer from poverty and from hunger by 2015. This commitment is another instance
      of the international community through the UN system yet again renewing its
      efforts and setting a target and a time frame to deal with the global problem of
      hunger, poverty and malnutrition. To date, the efforts to reduce global hunger in
      the developing world have fallen far short of the pace required to meet these
      targets. There has no doubt been some progress and several countries in the
      developing world have proved that success is possible. The economic and societal
      costs to developing countries of not taking decisive action, and thus failing to
      achieve a reduction in hunger and undernutrition, including micronutrient
      malnutrition costs, are that every year five million children lose their lives,
      220 million disability-adjusted life years are lost as a result of childhood and
      maternal undernutrition and billions of dollars are lost in productivity and
      incomes in these countries. Alongside this perennial problem in developing
      societies are emerging new epidemics of diet-related diseases resulting from the
      profound demographic changes, urbanization and the economic transition that is
      transforming and globalizing the food systems in these countries. Thus, many
      developing countries are facing new and additional challenges of co-existing
      hunger alongside the emergence of other forms of malnutrition. Meeting the WFS
      and MDG targets of achieving the goal of halving global hunger is urgent, and the
      question that needs to be addressed is not whether the international community
      can achieve this goal in time but whether it can afford not to.

PMID- 16441940
TI  - The fibre-folate debate in colo-rectal cancer.
AB  - Intervention and prospective studies showing no effect of fibre in protection
      against colo-rectal cancer have challenged consensus recommendations that
      population intakes of fibre should be increased to reduce the risk of colo-rectal
      cancer. The European Prospective Investigation of Cancer and Nutrition (EPIC) of
      519 978 individuals aged 25-70 years is the largest prospective study of diet and
      cancer to date worldwide. It incorporates ten different European countries in
      order to increase heterogeneity in dietary habits and calibration procedures to
      reduce measurement error. Data for 1065 reported cases of colo-rectal cancer were
      reported in 2003. There was a 40% reduction in risk for the highest quintile v.
      lowest quintile of fibre in food after calibration. It has been suggested that
      these effects were a result of confounding by folate and other factors. Although
      there are a number of hypotheses to explain why folate should be protective in
      colo-rectal cancer, a meta-analysis has shown that folate in food may be
      protective but there is no effect of total folate (i.e. food plus supplements).
      In a further analysis of 1826 cases in EPIC, identified in the latest follow-up,
      the inclusion of an additional 761 cases has confirmed the previously published
      results, with a strong and significant reduction in colo-rectal cancer of
      approximately 9% reduction in risk for each uncalibrated quintile increase in
      fibre (P<0.001 for linear trend) compared with an 8% reduction in the previous
      report, which had not been adjusted for folate. Inclusion of the other covariates
      (physical activity, alcohol, smoking and red and processed meat) with folate has
      confirmed this significant inverse association for colon cancer and strengthened
      the association with left-sided colon cancer (P < 0.001).

PMID- 16441941
TI  - Whole grains and CVD risk.
AB  - There is an increasing body of evidence, including that from prospective
      population studies and epidemiological observational studies, suggesting a strong
      inverse relationship between increased consumption of wholegrain foods and
      reduced risk of CVD. This evidence has translated into specific dietary
      recommendations in the USA to consume at least three servings of whole grain per
      d, and has informed the development of specific health claims for wholegrain
      foods both in the USA and in Europe. Wholegrain foods are rich sources of many
      nutrients and phytochemicals, including complex carbohydrates, dietary fibre,
      minerals, vitamins, antioxidants and phyto-oestrogens such as lignans. Many of
      these components are lost from the grain during processing and although some may
      be replaced (such as in the mandatory fortification of white flour), this
      practice ignores the possible synergistic effects of the 'natural' constituents.
      The notion that wholegrain foods are simply a source of dietary fibre has been
      dispelled, although the additional components that contribute to the health
      benefits have not been clearly identified. In addition, the mechanisms by which
      wholegrain foods may have their effect are poorly understood. At present there
      are few strictly-controlled intervention studies that have confirmed a beneficial
      effect of increased consumption of wholegrain foods, demonstrated the level of
      consumption required to elicit a beneficial effect or provided evidence of modes
      of action. Although wholegrain foods are considered amongst the healthiest food
      choices available, their consumption falls well below current recommendations,
      which have been based mainly on epidemiological evidence. Well-controlled
      intervention studies are needed to provide more detailed mechanistic evidence to
      support the health claims and findings which can be used to develop effective
      public health strategies to promote whole-grain consumption.

PMID- 16441942
TI  - Health effects of vegetarian and vegan diets.
AB  - Vegetarian diets do not contain meat, poultry or fish; vegan diets further
      exclude dairy products and eggs. Vegetarian and vegan diets can vary widely, but
      the empirical evidence largely relates to the nutritional content and health
      effects of the average diet of well-educated vegetarians living in Western
      countries, together with some information on vegetarians in non-Western
      countries. In general, vegetarian diets provide relatively large amounts of
      cereals, pulses, nuts, fruits and vegetables. In terms of nutrients, vegetarian
      diets are usually rich in carbohydrates, n-6 fatty acids, dietary fibre,
      carotenoids, folic acid, vitamin C, vitamin E and Mg, and relatively low in
      protein, saturated fat, long-chain n-3 fatty acids, retinol, vitamin B(12) and
      Zn; vegans may have particularly low intakes of vitamin B(12) and low intakes of
      Ca. Cross-sectional studies of vegetarians and vegans have shown that on average
      they have a relatively low BMI and a low plasma cholesterol concentration; recent
      studies have also shown higher plasma homocysteine concentrations than in non
      vegetarians. Cohort studies of vegetarians have shown a moderate reduction in
      mortality from IHD but little difference in other major causes of death or all
      cause mortality in comparison with health-conscious non-vegetarians from the same
      population. Studies of cancer have not shown clear differences in cancer rates
      between vegetarians and non-vegetarians. More data are needed, particularly on
      the health of vegans and on the possible impacts on health of low intakes of long
      chain n-3 fatty acids and vitamin B(12). Overall, the data suggest that the
      health of Western vegetarians is good and similar to that of comparable non
      vegetarians.

PMID- 16441943
TI  - Long-chain n-3 PUFA: plant v. marine sources.
AB  - Increasing recognition of the importance of the long-chain n-3 PUFA, EPA and DHA,
      to cardiovascular health, and in the case of DHA to normal neurological
      development in the fetus and the newborn, has focused greater attention on the
      dietary supply of these fatty acids. The reason for low intakes of EPA and DHA in
      most developed countries (0.1-0.5 g/d) is the low consumption of oily fish, the
      richest dietary source of these fatty acids. An important question is whether
      dietary intake of the precursor n-3 fatty acid, alpha-linolenic acid (alphaLNA),
      can provide sufficient amounts of tissue EPA and DHA by conversion through the n
      3 PUFA elongation-desaturation pathway. alphaLNA is present in marked amounts in
      plant sources, including green leafy vegetables and commonly-consumed oils such
      as rape-seed and soyabean oils, so that increased intake of this fatty acid would
      be easier to achieve than via increased fish consumption. However, alphaLNA
      feeding studies and stable-isotope studies using alphaLNA, which have addressed
      the question of bioconversion of alphaLNA to EPA and DHA, have concluded that in
      adult men conversion to EPA is limited (approximately 8%) and conversion to DHA
      is extremely low (<0.1%). In women fractional conversion to DHA appears to be
      greater (9%), which may partly be a result of a lower rate of utilisation of
      alphaLNA for beta-oxidation in women. However, up-regulation of the conversion of
      EPA to DHA has also been suggested, as a result of the actions of oestrogen on
      Delta6-desaturase, and may be of particular importance in maintaining adequate
      provision of DHA in pregnancy. The effect of oestrogen on DHA concentration in
      pregnant and lactating women awaits confirmation.

PMID- 16441944
TI  - Zinc: the missing link in combating micronutrient malnutrition in developing
      countries.
AB  - The first cases of human Zn deficiency were described in the 1960s in the Middle
      East. Nevertheless, it was not until 2002 that Zn deficiency was included as a
      major risk factor in the global burden of disease, and only in 2004 did
      WHO/UNICEF include Zn supplements in the treatment of acute diarrhoea. Despite
      this recognition Zn is still not included in the UN micronutrient priority list,
      an omission that will continue to hinder efforts to reduce child and maternal
      mortality, combat HIV/AIDS, malaria and other diseases and achieve the UN
      Millennium Development Goals for improved nutrition in developing countries.
      Reasons for this omission include a lack of awareness of the importance of Zn in
      human nutrition, paucity of Zn and phytate food composition values and
      difficulties in identifying Zn deficiency. Major factors associated with the
      aetiology of Zn deficiency include dietary inadequacies, disease states inducing
      excessive losses or impairing utilization and physiological states increasing Zn
      requirements. To categorize countries according to likely risk of Zn deficiency
      the International Zinc Nutrition Consultative Group has developed indirect
      indicators based on the adequacy of Zn in the national food supplies and/or
      prevalence of childhood growth stunting. For countries identified as at risk
      confirmation is required through direct measurements of dietary Zn intake and/or
      serum Zn in a representative sample. Finally, in at risk countries either
      national or targeted Zn interventions such as supplementation, fortification,
      dietary diversification or modification, or biofortification should be
      implemented, where appropriate, by incorporating them into pre-existing
      micronutrient intervention programmes.

PMID- 16441945
TI  - Biological effects of fruit and vegetables.
AB  - A strong and persistent effect of plant-derived foods on the prevention of
      lifestyle diseases has emerged from observational studies. Several groups of
      constituents in plants have been identified as potentially health promoting in
      animal studies, including cholesterol-lowering factors, antioxidants, enzyme
      inducers, apoptosis inducers etc. In human intervention studies the dose levels
      achieved tend to be lower than the levels found to be effective in animals and
      sampling from target organs is often not possible. A controlled dietary human
      intervention study was performed with forty-three volunteers, providing 600 g
      fruit and vegetables/d or in the controls a carbohydrate-rich drink to balance
      energy intake. Surrogate markers of oxidative damage to DNA, protein and lipids,
      enzymic defence and lipid metabolism were determined in blood and urine. It was
      found that a high intake of fruit and vegetables tends to increase the stability
      of lipids towards oxidative damage. Markers of oxidative enzymes indicate a
      steady increase in glutathione peroxidase (GPX1) activity in erythrocytes during
      intervention with fruit and vegetables but there is no effect on GPX1
      transcription levels in leucocytes. No change occurs in glutathione-conjugating
      or -reducing enzyme activities in erythrocytes or plasma, and there are no
      effects on the transcription of genes involved in phase 2 enzyme induction or DNA
      repair in leucocytes. Fruit and vegetable intake decreases the level of total
      cholesterol and LDL-cholesterol, but does not affect sex hormones. In conclusion,
      it has been shown that total cholesterol and LDL-cholesterol, markers of
      peripheral lipid oxidation, and erythrocyte GPX1 activity are affected by high
      intakes of fruit and vegetables. This finding provides support for a protective
      role of dietary fruit and vegetables against CVD.

PMID- 16441946
TI  - Vegetable-derived isothiocyanates: anti-proliferative activity and mechanism of
      action.
AB  - Many isothiocyanates (ITC), which are available to human subjects mainly through
      consumption of cruciferous vegetables, demonstrate strong cancer-preventive
      activity in animal models. Human studies also show an inverse association between
      consumption of ITC and risk of cancer in several organs. Whereas earlier studies
      primarily focused on the ability of ITC to inhibit carcinogen-activating enzymes
      and induce carcinogen-detoxifying enzymes, more recent investigations have shown
      that ITC inhibit the proliferation of tumour cells both in vitro and in vivo by
      inducing apoptosis and arresting cell cycle progression. ITC cause acute cellular
      stress, which may be the initiating event for these effects. These findings shed
      new light on the mechanism of action of ITC and indicate that ITC may be useful
      both as cancer-preventive and therapeutic agents. ITC activate caspase 9-mediated
      apoptosis, apparently resulting from mitochondrial damage, and also activate
      caspase 8, but the mechanism remains to be defined. Cell cycle arrest caused by
      ITC occurs mainly in the G2/M phase, and both the G2 and M phases are targetted;
      critical G2-phase regulators, including cyclin B1, cell division cycle (Cdc) 2
      and Cdc25C, are down regulated or inhibited, and tubulin polymerization and
      spindle assembly are disrupted. Moreover, ITC are metabolized in vivo through the
      mercapturic acid pathway, giving rise to thiol conjugates (dithiocarbamates).
      Studies show that these dithiocarbamates are similar to their parent ITC in
      exerting anti-proliferative activity. Taken together, dietary ITC are highly
      promising anti-cancer agents, capable of targetting multiple cellular components
      that are important for tumour cell survival and proliferation.

PMID- 16441947
TI  - Critical review of health effects of soyabean phyto-oestrogens in post-menopausal
      women.
AB  - A consensus view of soyabean phyto-oestrogens in clinical interventions in post
      menopausal women is presented that is based on data from the EU-funded project
      Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given
      as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or
      pure compounds. A comprehensive literature search was conducted with well-defined
      inclusion or exclusion criteria. For areas for which substantial research exists
      only placebo-controlled double-blind randomised controlled trials (RCT) conducted
      on healthy post-menopausal women were included. For emerging areas all available
      human studies in post-menopausal women were reviewed. In order to make cross
      comparisons between studies the doses of isoflavones were calculated as aglycone
      equivalents. There is a suggestion, but no conclusive evidence, that isoflavones
      from the sources studied so far have a beneficial effect on bone health. The
      consumption of whole-soyabean foods and soyabean-protein isolates has some
      beneficial effects on lipid markers of cardiovascular risk. The consumption of
      isolated isoflavones does not affect blood lipid levels or blood pressure,
      although it may improve endothelial function. For menopausal symptoms there is
      currently limited evidence that soyabean-protein isolates, soyabean foods or red
      clover (Trifolium pratense L.) extract are effective but soyabean isoflavone
      extracts may be effective in reducing hot flushes. There are too few RCT studies
      to reach conclusions on the effects of isoflavones on breast cancer, colon
      cancer, diabetes or cognitive function. The health benefits of soyabean phyto
      oestrogens in healthy post-menopausal women are subtle and even some well
      designed studies do not show protective effects. Future studies should focus on
      high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast
      cancer and bone health.

PMID- 16441948
TI  - Is there a role for dietary salicylates in health?
AB  - Acetylsalicylic acid (aspirin; 2-acetoxybenzoic acid) has been used for >100
      years for pain relief and to treat inflammatory conditions and fevers. More
      recently, regular intake has been associated with decreased incidence of certain
      cancers, particularly colon cancer. After absorption aspirin is very rapidly
      hydrolysed to salicylic acid (2-hydroxybenzoic acid). The anti-cancer effects of
      aspirin may be a result of salicylic acid reducing the transcription of
      prostaglandin H(2)-synthase and thereby the synthesis of pro-inflammatory and
      potentially-neoplastic prostaglandins. Salicylic acid is widely present in plants
      and functions as a hormonal mediator of the systemic acquired resistance response
      to pathogen attack and environmental stress. Thus, it is present in a large range
      of fruit, vegetables, herbs and spices of dietary relevance. Consequently, the
      recognised effect of consuming fruit and vegetables on lowering risk of colon
      cancer may be partly attributable to salicylates in plant-based foods. The
      present review discusses which types of fruit and vegetables are the richest
      source of salicylates and whether they are sufficiently released from the food
      matrix to modify the key cellular events associated with the pathogenesis of
      colon cancer.

PMID- 16441950
TI  - Does genotype and equol-production status affect response to isoflavones? Data
      from a pan-European study on the effects of isoflavones on cardiovascular risk
      markers in post-menopausal women.
AB  - The increase in CVD incidence following the menopause is associated with
      oestrogen loss. Dietary isoflavones are thought to be cardioprotective via their
      oestrogenic and oestrogen receptor-independent effects, but evidence to support
      this role is scarce. Individual variation in response to diet may be considerable
      and can obscure potential beneficial effects in a sample population; in
      particular, the response to isoflavone treatment may vary according to genotype
      and equol-production status. The effects of isoflavone supplementation (50 mg/d)
      on a range of established and novel biomarkers of CVD, including markers of lipid
      and glucose metabolism and inflammatory biomarkers, have been investigated in a
      placebo-controlled 2 x 8-week randomised cross-over study in 117 healthy post
      menopausal women. Responsiveness to isoflavone supplementation according to (1)
      single nucleotide polymorphisms in a range of key CVD genes, including oestrogen
      receptor (ER) alpha and beta and (2) equol-production status has been examined.
      Isoflavones supplementation was found to have no effect on markers of lipids and
      glucose metabolism. Isoflavones improve C-reactive protein concentrations but do
      not affect other plasma inflammatory markers. There are no differences in
      response to isoflavones according to equol-production status. However,
      differences in HDL-cholesterol and vascular cell adhesion molecule 1 response to
      isoflavones v. placebo are evident with specific ERbeta genotypes. In conclusion,
      isoflavones have beneficial effects on C-reactive protein, but not other
      cardiovascular risk markers. However, specific ERbeta gene polymorphic subgroups
      may benefit from isoflavone supplementation.

PMID- 16441949
TI  - Developmental programming of health and disease.
AB  - The environment encountered in fetal and neonatal life exerts a profound
      influence on physiological function and risk of disease in adult life.
      Epidemiological evidence suggests that impaired fetal growth followed by rapid
      catch-up in infancy is a strong predictor of obesity, hypertension, non-insulin
      dependent diabetes and CHD. Whilst these associations have been widely accepted
      to be the product of nutritional factors operating in pregnancy, evidence from
      human populations to support this assertion is scarce. Animal studies clearly
      demonstrate that there is a direct association between nutrient imbalance in
      fetal life and later disease states, including hypertension, diabetes, obesity
      and renal disease. These associations are independent of changes in fetal growth
      rates. Experimental studies examining the impact of micro- or macronutrient
      restriction and excess in rodent pregnancy provide clues to the mechanisms that
      link fetal nutrition to permanent physiological changes that promote disease.
      Exposure to glucocorticoids in early life appears to be an important consequence
      of nutrient imbalance and may lead to alterations in gene expression that have
      major effects on tissue development and function. Epigenetic mechanisms,
      including DNA methylation, may also be important processes in early-life
      programming.

PMID- 16441951
TI  - Maternal nutrient restriction alters renal development and blood pressure
      regulation of the offspring.
AB  - Studies have shown that the risk of hypertension in adulthood can be affected by
      the in utero environment. It is established that hypertension is linked to
      compromised kidney function and that factors affecting organogenesis can increase
      the risk of later disease. Prostaglandins (PG) and growth factors are known to
      play an important role in regulating kidney function and renal organogenesis. The
      extent, however, to which global energy restriction (where all nutrients are
      reduced) of the mother can programme later blood pressure control or renal PG and
      growth factor status is unknown. A study is described that aimed to examine the
      long-term effects of maternal nutrient restriction (NR) and elucidate their
      relationship with compromised kidney development. First, it was necessary to
      establish animal models. A sheep model of 50% NR during specific stages of
      gestation was used to investigate fetal renal development, whilst a rat model of
      50% NR throughout pregnancy was used to investigate postnatal kidney development
      and adult functioning. Molecular analysis has shown that expression of the growth
      hormone-insulin-like growth factor (GH-IGF) axis is affected by NR in the fetal
      sheep kidneys, and that changes are dependent on the timing of NR and whether the
      fetus is a singleton or a twin. Analysis of the kidneys from the rat model has
      shown nutritional differences in the expression of PG receptors and the enzymes
      responsible for PG synthesis and degradation that persist into adulthood. In
      conclusion, NR does affect the GH-IGF and PG axes, and these changes may be
      important in the nutritional programming of renal functioning and adult blood
      pressure control.

PMID- 16441952
TI  - Glycaemic index and metabolic disease risk.
AB  - There is growing evidence that the type of carbohydrate consumed is important in
      relation to metabolic disease risk, and there is currently particular interest in
      the role of low-glycaemic-index (GI) foods. Observational studies have associated
      low-GI diets with decreased risk of type 2 diabetes and CHD, and improvements in
      various metabolic risk factors have been seen in some intervention studies.
      However, findings have been mixed and inconsistent. There are a number of
      plausible mechanisms for the effects of these foods on disease risk, which arise
      from the differing metabolic responses to low- and high-GI foods, with low-GI
      foods resulting in reductions in hyperglycaemia, hyperinsulinaemia and late
      postprandial circulating NEFA levels. Low-GI foods may also increase satiety and
      delay the return of hunger compared with high-GI foods, which could translate
      into reduced energy intake at later time points. However, the impact of a low-GI
      diet on body weight is controversial, with many studies confounded by dietary
      manipulations that differ in aspects other than GI. There is currently much
      interest in GI from scientists, health professionals and the public, but more
      research is needed before clear conclusions can be drawn about relationships with
      metabolic disease risk.

PMID- 16441953
TI  - Cruciferous vegetables and colo-rectal cancer.
AB  - Cruciferous vegetables have been studied extensively for their chemoprotective
      effects. Although they contain many bioactive compounds, the anti-carcinogenic
      actions of cruciferous vegetables are commonly attributed to their content of
      glucosinolates. Glucosinolates are relatively biologically inert but can be
      hydrolysed to a range of bioactive compounds such as isothiocyanates (ITC) and
      indoles by the plant-based enzyme myrosinase, or less efficiently by the colonic
      microflora. A number of mechanisms whereby ITC and indoles may protect against
      colo-rectal cancer have been identified. In experimental animals cruciferous
      vegetables have been shown to inhibit chemically-induced colon cancer. However,
      the results of recent epidemiological cohort studies have been inconsistent and
      this disparity may reflect a lack of sensitivity of such studies. Possible
      explanations for the failure of epidemiological studies to detect an effect
      include: assessment of cruciferous vegetable intake by methods that are subject
      to large measurement errors; the interaction between diet and genotype has not
      been considered: the effect that post-harvest treatments may have on biological
      effects of cruciferous vegetables has not been taken into account.

PMID- 16441954
TI  - Cachexia and chronic respiratory failure: lessons from ventilatory support.

PMID- 16441955
TI  - Infant aerosol holding chamber face masks: not all are born equal!

PMID- 16441956
TI  - Weight gain in cachectic COPD patients receiving noninvasive positive-pressure
      ventilation.
AB  - BACKGROUND: In chronic obstructive pulmonary disease (COPD), body mass index
      (BMI) is an important predictor of survival. Little is known about the prevalence
      of malnutrition or longitudinal changes of BMI in patients undergoing noninvasive
      positive-pressure ventilation (NPPV). METHODS: In a cohort study of 141 patients
      with COPD and severe chronic respiratory failure (mean forced expiratory volume
      in the first second [FEV1] 0.80 +/- 0.27 L, mean P(aCO2) 55.6 +/- 8.8 mm Hg), we
      investigated nutritional status in relation to respiratory impairment. Changes in
      BMI were evaluated at 6 and 12 months after initiation of NPPV. RESULTS:
      Malnutrition, indicated by a BMI of < 20 kg/m2, was found in 20.6% of the
      patients. BMI was significantly correlated with the severity of respiratory
      impairment, especially with hyperinflation (residual volume divided by total lung
      capacity, r = -0.55, p < 0.001). In malnourished patients (BMI < 20 kg/m2) there
      was a significant increase in body weight after 6 months (6.2 +/- 12.5%, p <
      0.05) and 12 months (12.8 +/- 16.0%, p < 0.01), whereas there were no significant
      changes in the overall study population. Furthermore, there was no correlation
      between changes in BMI and changes in blood-gas values, lung function, or
      inspiratory muscle function, either in the entire patient group or in the
      subgroup of malnourished patients. CONCLUSIONS: In COPD with chronic respiratory
      failure, malnutrition is common and strongly related to hyperinflation. After
      initiation of NPPV, a significant weight gain is observed in malnourished COPD
      patients.

PMID- 16441957
TI  - Evaluation of a new method for measurement of minute ventilation recovery time.
AB  - PURPOSE: To determine if the measurement of minute ventilation recovery time (V
      (E)RT), a recently proposed predictor of extubation outcome, can be reproduced
      using a more practical, simpler method. METHODS: A case series with convenience
      sampling was performed in the surgical intensive care unit of a tertiary-care
      hospital. Nineteen patients were enrolled during weaning from mechanical
      ventilation, prior to the initial extubation attempt. Within-subject comparisons
      of V (E)RT were performed, using 2 alternative methods for measuring baseline V
      (E) and one alternative method for determining the threshold for recovery of V
      (E) during the final spontaneous breathing trial prior to extubation. Comparison
      methods for baseline V (E) included an 8-hour average and the last V (E)
      measurement prior to the spontaneous breathing trial. The alternative threshold
      for defining recovery of V (E) was 100% of the baseline value (vs 110% in the
      original method). RESULTS: The study subjects were primarily cardiac surgery
      patients (63%) and were ventilated for a median of 5 days prior to extubation. V
      (E)RT calculated using the 8-hour average or the last V (E) measurement prior to
      the spontaneous breathing trial as baseline, and a threshold of 100% of baseline
      V (E) to define recovery most closely approximated V (E)RT obtained by the
      original method and similarly classified patients at high risk for reintubation
      (kappa statistic = 0.78 +/- 0.2). CONCLUSIONS: V (E)RT can be determined using a
      simpler method for measuring both baseline V (E) and the recovery threshold.
      These methodological modifications may increase the feasibility of measuring V
      (E)RT, while reproducing the results obtained by the original method.

PMID- 16441958
TI  - Force-dependent static dead space of face masks used with holding chambers.
AB  - BACKGROUND: Pressurized metered-dose inhalers with valved holding chambers and
      masks are commonly used for aerosol delivery in children. Drug delivery can
      decrease when the dead-space volume (DSV) of the valved holding chamber is
      increased, but there are no published data evaluating force-dependent DSV among
      different masks. METHODS: Seven masks were studied. Masks were sealed at the
      valved holding chamber end and filled with water to measure mask volume. To
      measure mask DSV we used a mannequin of 2-year-old-size face and we applied the
      mask with forces of 1.5, 3.5, and 7 pounds. Mask seal was determined by direct
      observation. Intra-brand analysis was done via analysis of variance. RESULTS: At
      3.5 pounds of force, the DSV ranged from 29 mL to 100 mL, with 3 masks having DSV
      of < 50 mL. The remaining masks all had DSV > 60 mL. At 3.5 pounds of force, DSV
      percent of mask volume ranged from 33.7% (Aerochamber, p < 0.01 compared with
      other masks) to 100% (Pocket Chamber). DSV decreased with increasing force with
      most of the masks, and the slope of this line was inversely proportional to mask
      flexibility. Mask fit was 100% at 1.5 pounds of force only with the Aerochamber
      and Optichamber. Mask fit was poorest with the Vortex, Pocket Chamber, and
      BreatheRite masks. CONCLUSION: Rigid masks with large DSV might not be not
      suitable for use in children, especially if discomfort from the stiff mask makes
      its use less acceptable to the child.

PMID- 16441959
TI  - Procedure to normalize data for benchmarking.
AB  - INTRODUCTION: The hospital billing system is usually the source for reporting
      activity counts used in benchmarking efforts. Because billing is associated with
      a specific procedure, benchmarking data are often reported as procedure-days,
      procedure-shifts, or procedure-hours. Normalizing (usually to procedure-days) is
      required when comparing data for benchmarking purposes. For an institution that
      uses hourly billing, simply dividing procedure-hours by 24 (or procedure-shifts
      by 2 or 3) will underestimate the procedure-days reported by a daily billing
      system, because daily billing systems use the convention that any fractional day
      of service is rounded up to the next higher day. The purposes of this study were:
      (1) to simulate sets of data and determine the expected error with conversion by
      simple division, (2) to derive a more accurate procedure for normalizing
      benchmarking data, and (3) to compare the new normalization procedure to simple
      division, using simulated and actual data. METHODS: A reference population of
      simulated patient data was created using a spreadsheet to generate random start
      times paired with actual procedure durations (eg, hours of mechanical
      ventilation) for 5,000 patients. The spreadsheet calculated "true" billable
      procedure-days and procedure-shifts from the simulated procedure-hours. Next, a
      resampling procedure was used to simulate the effect of submitting benchmarking
      data based on various numbers of patients. The resulting sets of data were used
      to examine the association between sample size and conversion error when
      converting from procedure-hours to procedure-days and to generate an alternative
      conversion procedure that uses linear regression to estimate procedure-days from
      procedure-hours. An additional regression equation was generated from actual
      patient data, using simultaneously recorded procedure-hours and procedure-days.
      The set of mean conversion errors for the 2 regression equations was compared
      using the Mann-Whitney rank sum test. RESULTS: In general, conversion errors
      (both systematic and random errors) were smaller with larger sample sizes and
      with longer service periods, approaching an asymptote at a sample size greater
      than about 20. Using division, the conversion errors for a sample size of 100
      were +/-16% for hourly reporting, +/-11% for 8-hour shifts, and +/-8% for 12-hour
      shifts. The regression equations for conversion derived from simulated data were
      as follows. For hourly billing, procedure-days = +/-0.237 + (0.049) (procedure
      hours). For 8-hour shifts, procedure-days = +/-0.205 + (0.372) (procedure
      shifts). For 12-hour shifts, procedure-days = +/-0.114 + (0.541) (procedure
      shifts). Using those regression equations, the conversion errors for a sample
      size of 100 were +/-1% for hourly reporting, +/-0.2% for 8-hour shifts, and +/
      0.2% for 12-hour shifts. The regression equation (for hourly billing) derived
      from simulated data gave better results than did the equation derived from actual
      data (median error 0.39 vs +/-2.92, p = 0.013).

PMID- 16441960
TI  - Practical problems with aerosol therapy in COPD.
AB  - Inhaled aerosol drugs commonly used by patients with chronic obstructive
      pulmonary disease include short-acting and long-acting bronchodilators, as well
      as corticosteroids. These agents are available in a variety of inhaler devices,
      which include metered-dose inhalers (MDI), breath-actuated MDIs, nebulizers, and,
      currently, 5 different models of dry powder inhaler (DPI). There is evidence to
      suggest that multiple inhaler types cause confusion among patients and increase
      errors in patient use. Problems with MDIs include failure to coordinate
      inhalation with actuation of the MDI, inadequate breath-hold, and inappropriately
      fast inspiratory flow. Lack of a dose counter makes determining the number of
      remaining doses in an MDI problematic. Patient misuse of MDIs is compounded by
      lack of knowledge of correct use among health-care professionals. Several factors
      often seen with elderly patients have been identified as predictive of incorrect
      use of MDIs. These include mental-state scores, hand strength, and ideomotor
      dyspraxia. Holding chambers and spacers are partially intended to reduce the need
      for inhalation-actuation coordination with MDI use. However, such add-on devices
      can be subject to incorrect assembly. Possible delays between MDI actuation and
      inhalation, rapid inspiration, chamber electrostatic charge, and firing multiple
      puffs into the chamber can all reduce the availability of inhaled drug. Because
      they are breath-actuated, DPIs remove the need for inhalation-actuation
      synchrony, but there is evidence that patient errors in use of DPIs may be
      similar to those with MDIs. One of the biggest problems is loading and priming
      the DPI for use, and this may be due to the fact that every DPI model in current
      use is different. Medical personnel's knowledge of correct DPI use has also been
      shown to be lacking. The optimum inhalation profiles are different for the
      various DPIs, but, generally, chronic obstructive pulmonary disease patients have
      been shown to achieve a minimum therapeutic dose, although the inhaled amount may
      be suboptimal. A limitation of DPIs that have multidose powder reservoirs (eg,
      the Turbuhaler) is ambient humidity, which can reduce the released dose. Small
      volume nebulizers are limited by bulk, treatment time, and variable performance,
      but are easy for patients to use. Important features identified by patients for
      an ideal inhaler are ease of use during an attack, dose counter, and general ease
      of use and learning. A breath-actuated-pMDI, such as the Autohaler, ranked at the
      top of inhaler preference in a study of 100 patients with airflow obstruction,
      compared to DPIs and MDIs. Short of a universal simple inhaler, patient and
      caregiver education remains the best solution to correct patient errors in use.

PMID- 16441961
TI  - Surgical options for patients with COPD: sorting out the choices.
AB  - Surgical procedures designed to improve pulmonary function and quality of life of
      patients with advanced emphysema have been attempted for more than a century. Of
      the many attempted procedures, only giant bullectomy, lung transplantation, and
      lung-volume-reduction surgery have withstood the test of time and are currently
      being practiced. This article reviews each of these procedures and also develops
      a rational approach to selecting appropriate candidates for these 3
      interventions.

PMID- 16441962
TI  - Privacy and medical information on the Internet.
AB  - Health-care consumers are beginning to realize the presence and value of health
      care information available on the Internet, but they need to be aware of risks
      that may be involved. In addition to delivering information, some Web sites
      collect information. Though not all of the information might be classified as
      protected health information, consumers need to realize what is collected and how
      it might be used. Consumers should know a Web site?'s privacy policy before
      divulging any personal information. Health-care providers have a responsibility
      to know what information they are collecting and why. Web servers may collect
      large amounts of visitor information by default, and they should be modified to
      limit data collection to only what is necessary. Providers need to be cognizant
      of the many regulations concerning collection and disclosure of information
      obtained from consumers. Providers should also provide an easily understood
      privacy policy for users.

PMID- 16441963
TI  - Generational changes on the draw-a-man test: a comparison of Brazilian urban and
      rural children tested in 1930, 2002 and 2004.
AB  - Although gains in generational intelligence test scores have been widely
      demonstrated around the world, researchers still do not know what has caused
      them. The cognitive stimulation and nutritional hypotheses summarize the several
      diverse potential causes that have been considered. This article analyses data
      for a sample of 499 children tested in 1930 and one equivalent sample of 710
      children tested 72 years later, the largest gap ever considered. Both samples
      comprised children aged between 7 and 11 who were assessed by the Draw-a-Man test
      in the city of Belo Horizonte, Brazil. Further, one additional sample of 132
      children was assessed in 2004 in a rural area very similar in several diverse
      factors to the 1930 urban sample. The results are consistent with both the
      cognitive stimulation and the nutritional hypotheses.

PMID- 16441964
TI  - How intellectual is chess? -- a reply to Howard.
AB  - Howard's (2005) claim that male dominance in chess is 'consistent with the
      evolutionary psychology view that males predominate at high achievement levels at
      least partly because of ability differences' (p. 378) is based on the premise
      that top level chess skill depends on a high level of IQ and visuospatial
      abilities. This premise is not supported by empirical evidence. In 1927 Djakow et
      al. first showed that world-class chess players do not have exceptional
      intellectual abilities. This finding has subsequently been confirmed many times.
      Different participation rates, or differences in the amount of practice,
      motivation and interest for chess in male and female chess players, may provide a
      better explanation for gender differences in chess performance.

PMID- 16441965
TI  - IQ, visuospatial ability and the gender divide: a reply to Bilalic and Mcleod.
AB  - Bilalic and McLeod's arguments fall short on several grounds. There are excellent
      logical reasons to expect strong ability/chess expertise links and specific
      research evidence to date is sparse, with mixed findings. Data are presented from
      Georgia, which has a high female participation rate in chess, which suggest that
      differing gender motivation levels and participation rates impact relatively
      little on chess performance differences at the extreme.

PMID- 16441966
TI  - Child immunization in Vietnam: situation and barriers to coverage.
AB  - This paper addresses the overall performance and inequalities in the immunization
      of children in Vietnam. Descriptive and logistic analysis of cross-national
      demographic and health data was used to examine inequality in immunization,
      identify the most vulnerable groups in immunization coverage, and identify the
      gap in coverage between hard-to-access people and the remainder of the
      population. The gap in the coverage was found to occur primarily in vulnerable
      groups such as the poor minority or poor rural children. No evidence was found of
      a difference in immunization coverage because of sex or birth order. However, the
      age of children showed a significant influence on the rate of immunization.
      Mother's education and regular watching of television had a significant influence
      on child immunization. In order to improve child immunization coverage in
      Vietnam, efforts should be concentrated on poor children from minority groups and
      those living in rural areas, especially remote ones. Community development,
      investment for immunization and re-organization of immunization services at the
      grassroots level are also key factors to remove the barriers to immunization for
      vulnerable populations in Vietnam.

PMID- 16441967
TI  - Social networks and inflammatory markers in the Framingham Heart Study.
AB  - Lack of social integration predicts coronary heart disease mortality in
      prospective studies; however, the biological pathways that may be responsible are
      poorly understood. The specific aims of this study were to examine whether social
      networks are associated with serum concentrations of the inflammatory markers
      interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion
      molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Participants
      in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were
      eligible for inclusion in the study. Social networks were assessed using the
      Berkman-Syme Social Network Index (SNI). Concentrations of IL-6, CRP, sICAM-1 and
      MCP-1 were measured in fasting serum samples. Multivariable linear regression
      analyses were used to assess the association of social networks with inflammatory
      markers adjusting for potential confounders including age, smoking, blood
      pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and
      antihypertensive medication, diabetes, cardiovascular disease, depression and
      socioeconomic status. Results found that the SNI was significantly inversely
      associated with IL-6 in men (p=0.03) after adjusting for potential confounders.
      In age-adjusted analyses, social networks also were significantly inversely
      associated with IL-6 for women (p=0.03) and were marginally to modestly
      associated with CRP and sICAM-1 for men (p=0.08 and 0.02, respectively), but
      these associations were not significant in the multivariate analyses. In
      conclusion, social networks were found to be inversely associated with
      interleukin-6 levels in men. The possibility that inflammatory markers may be
      potential mediators between social integration and coronary heart disease merits
      further investigation.

PMID- 16441969
TI  - Grommet insertion: a novel technique.
AB  - We describe a new technique for inserting grommets which is both easy to master
      and provides better visualization of the tympanic membrane. This is particularly
      helpful in patients with narrow ear canals.

PMID- 16441968
TI  - Post-tonsillectomy haemorrhage: a prospective, randomized, controlled clinical
      trial of cold dissection versus bipolar diathermy dissection.
AB  - OBJECTIVE: To determine whether bipolar dissection tonsillectomy is associated
      with a higher post-operative haemorrhage rate than cold dissection tonsillectomy.
      DESIGN: Prospective, randomized, controlled trial. SETTING: Otolaryngology
      department of a teaching hospital. PARTICIPANTS: Two hundred and forty-five
      patients undergoing elective tonsillectomy between July 2002 and November 2004.
      INTERVENTIONS: Patients were randomly assigned to either bipolar dissection or
      cold dissection (with bipolar haemostasis). MAIN OUTCOME MEASURES: Post-operative
      haemorrhage rates, management (conservative or surgical) and blood transfusion
      requirements were recorded. The grade of surgeon and history of quinsy were also
      recorded. RESULTS: One hundred and forty-one patients (58 per cent) were
      randomized to the bipolar dissection and 104 (42 per cent) to the cold dissection
      groups. Seventeen patients (12.1 per cent) in the bipolar dissection group and
      eight patients (7.7 per cent) in the cold dissection group suffered haemorrhage
      (p = 1.0; degrees of freedom (Df) 0.0; 95 per cent confidence intervals (CI) -0.1
      to 0.0). The haemorrhage rates for procedures conducted by senior house officers,
      specialist registrars and consultants were 11.4 per cent, 10.3 per cent and 5.0
      per cent, respectively. Two patients required surgical intervention, both from
      the bipolar dissection group. No patients required blood transfusion. A history
      of quinsy was not associated with an increased haemorrhage rate. CONCLUSION: The
      difference in haemorrhage rates between groups and surgeon grades did not reach
      statistical significance. Nonetheless the trend towards a greater incidence of
      haemorrhage in the bipolar group and in procedures conducted by more junior
      surgeons during the trial raised concerns. The results of the National
      Prospective Tonsillectomy Audit and our interim results have led us to abandon
      the trial and disallow the use of bipolar dissection in tonsillectomies performed
      by junior staff members.

PMID- 16441970
TI  - Schwannoma of the tympanic membrane.
AB  - Schwannoma arising from the tympanic membrane is a rare neoplasm. This report
      describes an external ear canal mass obscuring the tympanic membrane. A
      transcanal approach identified a tumour adhered to the tympanic membrane. The
      tumour was excised without myringoplasty. Pathology confirmed the diagnosis of
      schwannoma. Clinical examination revealed no evidence of recurrence during a
      follow-up period of one year. The possible origins of schwannoma of the tympanic
      membrane and lesion management are also discussed.

PMID- 16441971
TI  - Role of revision adenoidectomy in paediatric otolaryngological practice.
AB  - OBJECTIVES: We aimed to determine the need for revision adenoidectomy following
      the standard technique of blind curettage with digital palpation. METHODS: Within
      a district general hospital, we undertook a retrospective study of 3231 children
      who underwent adenoidectomy between 1996 and 2003, 53 of whom required revision
      adenoidectomy. The main outcome measure was the number of children needing
      revision adenoidectomy. RESULTS: A total of 53 children required a repeated
      operation for recurrence of symptoms (1.6 per cent); of these, 42 were for
      treatment of glue ear, five were for nasal symptoms and six were for adenoidal
      infection. CONCLUSION: Adenoidectomy performed without vision may be one of the
      reasons for recurrence of symptoms. Residual adenoids are acknowledged in the
      literature as one of the complications of the traditional technique. We highlight
      the fact that the need for revision adenoidectomy is not uncommon and suggest
      that we should improve our surgical technique in the UK by visualization of the
      postnasal space either by a mirror or an endoscope.

PMID- 16441972
TI  - An unusual case of primary extranodal non-Hodgkin's lymphoma in the muscles of
      facial expression.
AB  - Primary extra-nodal non-Hodgkin's lymphoma (NHL) of the skeletal muscles is a
      well recognized entity although such occurrences are not very common.
      Presentation in the muscles of the face has only rarely been described. We
      present a case of primary extra-nodal NHL in a non-immunocompromised patient
      involving only the muscles of facial expression and not extending to the oral
      cavity or sinonasal tract. The patient was subsequently treated with chemotherapy
      and at the time of writing remained in remission. We suggest that lymphoma should
      be considered among the causes for malignant infiltration of the muscles of the
      face.

PMID- 16441973
TI  - 'Choose and Book' in ENT: the GP perspective.
AB  - OBJECTIVES: 'Choose and Book' is a UK government initiative devised to allow a
      greater freedom of choice for National Health Service patients. The system is
      designed to give patients a choice of hospitals and appointment times, as well as
      giving their general practitioner (GP) more responsibility for appropriate
      prioritization. We set out to determine the attitudes of UK GPs to the new Choose
      and Book project and to assess the impact that these changes are likely to have
      on ENT practice. DESIGN: Postal questionnaire survey. METHODS: Five hundred GPs
      were sent a questionnaire about the planned Choose and Book referral project.
      RESULTS: Three hundred and eighty GPs (76 per cent) replied to the questionnaire
      after reminders were sent. Most were aware of the project and had been sent
      information about it. Of those who had heard of it, 61.5 per cent did not think
      it was a good thing. Most stated that both they and their patients were satisfied
      with current prioritization practices. Many GPs would be willing to delegate
      responsibility for prioritization to non-clinical staff. Important time and
      responsibility issues were identified. CONCLUSIONS: The majority of GPs were not
      in favour of Choose and Book. Many cited difficulties with time constraints and
      an inflexible system as factors that made Choose and Book unacceptable.

PMID- 16441974
TI  - Anaesthetists' and surgeons' estimation of preoperative anxiety by patients
      submitted for elective surgery in a university hospital.
AB  - BACKGROUND AND OBJECTIVE: Preoperative anxiety is a challenging concept in the
      preoperative care of patients. The hypothesis of this study was that the doctors
      are able to estimate their patients' preoperative anxiety. METHODS: A prospective
      clinical trial was performed on 67 adult patients and 26 paired anaesthetists and
      surgeons. The patients filled out two separate visual analogue scales for anxiety
      for the planned anaesthesia and surgery. After that the 'anxiety subscale' of the
      Hospital Anxiety and Depression's Scale was completed and a list of fearsome
      items was presented as the patients were asked to choose two conditions they
      considered the most frightening. Finally the patients were asked to select one or
      more items from a list of things, which they considered likely to relieve their
      preoperative anxiety. Similarly, the participating doctors were asked to estimate
      their patients' anxiety, guess their fearful conditions and their anxiety
      relieving requests. RESULTS: Median scores for anxiety as estimated with visual
      analogue scales by anaesthetists, surgeons and patients for anaesthesia were 34,
      36 and 6, respectively; and for surgery 53, 47 and 9, respectively. The anxiety
      subscale of the Hospital Anxiety and Depression's Scale 8.9 +/- 4.2, 8.6 +/- 4.6
      and 6.5 +/- 4.5 (mean +/- SD), respectively. Doctors' scores were significantly
      higher than the patients' scores (P < 0.05). Thus, the anaesthetists and the
      surgeons were unable to estimate their patients anxiety on any of the scales used
      (Kendall's tau < 0.25; P < 0.05). The proportion of correct estimation of the
      fearsome items was 20% for both the anaesthetists and the surgeons. CONCLUSIONS:
      Both anaesthetists and surgeons overestimated their patients' preoperative
      anxiety by a wide margin and poorly predicted their patients' feared conditions
      and their desire for relief of anxiety.

PMID- 16441975
TI  - Single-channel properties of volume-sensitive Cl- channel in ClC-3-deficient
      cardiomyocytes.
AB  - It is controversial whether the ClC-3 protein, which is one of the voltage
      dependent chloride channel ClC family members, is a candidate for the volume
      sensitive outwardly rectifying (VSOR) Cl(-) channel per se or its regulator.
      Here, for the first time, we examined the single-channel properties of the VSOR
      Cl(-) channel in ventricular myocytes isolated from ClC-3-deficient mice. The
      single-channel current induced by cell swelling exhibited Cl(-) selectivity, mild
      outward rectification, and an intermediate unitary conductance (around 38 pS). A
      Cl(-) channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS),
      reversibly inhibited the outward current. These single-channel properties were
      identical with those in ClC-3 expressing wild-type ventricular myocytes. These
      results indicate that the single-channel activity of the VSOR Cl(-) channel is
      independent of the expression of ClC-3 proteins in mouse ventricular myocytes.

PMID- 16441977
TI  - Gift authorship practices -- history, trends and remedies.

PMID- 16441976
TI  - Does higher red blood cell (RBC) lactate transporter activity explain impaired
      RBC deformability in sickle cell trait?
AB  - Lactate and H(+) are suggested to promote the sickling process in red blood cells
      (RBCs) containing hemoglobin S. We demonstrated greater activity of the RBC
      monocarboxylate cotransporter MCT-1, lower RBC deformability and impaired
      hematological indices in sickle cell trait (SCT) carriers compared to control
      subjects, suggesting an involvement of MCT-1 in hemorheological disturbances in
      SCT carriers.

PMID- 16441978
TI  - Intravenous tramadol vs ketorolac in laparoscopic dye test.
AB  - OBJECTIVE: To compare the quality of analgesia and side effects of I/V tramadol
      with a non-steroidal anti-inflammatory drug ketorolac in patients undergoing
      laparoscopic dye test. DESIGN: A single dose, double blind, randomized clinical
      trial. PLACE AND DURATION OF STUDY: The Day Care Surgical Unit at the Aga Khan
      University Hospital, Karachi. The duration was initially planned for 6 months but
      was completed from January 2001 to February 2002. PATIENTS AND METHODS: Sixty
      patients coming for laparoscopic dye test were randomized by convenient sampling.
      Patients were divided into two groups, A and B, who received intravenous tramadol
      or ketorolac respectively before induction of general anaesthesia. Patients were
      assessed in the postanaesthesia care unit for pain using the visual analogue
      scale (VAS), frequency of postoperative nausea and vomiting was observed by the
      investigator who remained blinded to the treatment given. Any patient found to
      have pain score >5 was given bolus of 10 mg pethidine in titrated doses. Study
      was continued for 6 hours postoperatively. Pain scores were analyzed by applying
      Chi-square test. RESULTS: Students impaired t-test was used to analyze
      demographic data, recovery time and hospital discharge, Mann Whitney was applied
      to analyze VAS scores. Categorical data i.e. nausea and vomiting was analyzed by
      using the Chi-square test (p-value >0.05). CONCLUSION: Study showed that tramadol
      is a better analgesic compared to ketorolac for patients undergoing day care
      gynaecological laparoscopic procedure.

PMID- 16441979
TI  - Management of parapharyngeal space tumours.
AB  - OBJECTIVE: To determine the role of clinical features, fine needle aspiration
      cytology (FNAC) and computed tomography (CT) scan in diagnosing parapharyngeal
      space (PPS) tumours and treatment options. DESIGN: A descriptive study. PLACE AND
      DURATION OF STUDY: From July 2000 to July 2002 at Pakistan Institute of Medical
      Sciences, Islamabad. PATIENTS AND METHODS: Patients diagnosed as having PPS
      tumours were studied. The medical record of patients was reviewed for their age,
      gender, clinical features, investigations (FNAC and CT scan) and treatment. The
      mean age, percentage of different clinical features and the sensitivity and
      specificity of FNAC was determined. RESULTS: The mean age of patients presenting
      with PPS tumours was 33.6 years. The most common clinical features were neck mass
      (93%) and bulge in lateral pharyngeal wall (80%). The CT scan showed exact
      location and extent of tumour in 11 out of 15 cases. The sensitivity and
      specificity of FNAC was 70% and 85% respectively. The most common tumours were
      neurogenic tumours (6) and salivary gland tumours (4). Surgery was performed in
      all except 2 patients with lymphoma in whom radiation and chemotherapy was
      recommended. CONCLUSION: This study indicates that PPS tumours are usually benign
      neurogenous and salivary gland tumours presenting with neck mass and bulge in
      oropharynx. FNAC and CT scan are important in diagnostic work up and treatment
      planning. Surgery has the best results in most cases.

PMID- 16441980
TI  - Insulin and glucagon ratio in the patho-physiology of diabetic ketoacidosis and
      hyperosmolar hyperglycemic non-ketotic diabetes.
AB  - OBJECTIVE: To assess the role of insulin / glucagon ratio in pathophysiology of
      diabetic ketoacidosis and hyperosmolar hyperglycemic non-ketotic diabetes.
      DESIGN: Case control, analytical study. PLACE AND DURATION OF STUDY: Military
      Hospital, Rawalpindi from September 2003 to August 2004. PATIENTS AND METHODS:
      The study included 7 patients with diabetic ketoacidosis, 3 patients with
      hyperosmolar hyperglycemic non-ketotic diabetes, 8 patients with uncontrolled
      type 1 diabetes mellitus and 12 patients with uncontrolled type 2 diabetes
      mellitus. Twenty non-diabetic persons having blood glucose level less than 6
      mmol/L were selected as control group. Patient s detailed history was taken and
      general physical examination was done. Plasma samples of all the patients and
      control subjects were assayed for plasma glucose, glycosylated hemoglobin, plasma
      insulin and glucagon levels. Presence or absence of ketone bodies in urine was
      also determined. RESULTS: Seven patients with diabetic ketoacidosis, 3 females
      and 4 males, were found to be hyperglycemic ( p<0.001 ), hypoinsulinemic ( p <
      0.05) and hyperglucagonemic ( p < 0.001 ) as compared to control group. Three
      patients with hyperosmolar hyperglycemic non-ketotic diabetes, 1 male and 2
      females, were hyperglycemic ( p < 0.001 ). Eight patients with uncontrolled type
      I diabetes mellitus, 6 males and 2 females, were having hyperglycemia (p< 0.001)
      along with hyperglucagonemia (p < 0.001). Twelve patients with uncontrolled type
      2 diabetes mellitus, 6 males and 6 females, were found to be hyperglycemic ( p <
      0.001 ) and hyperinsulinemic (p < 0.001) as compared to control group. The
      insulin / glucagon ratio was found to be 1 : 0.9 in diabetic ketoacidosis, 1:
      0.15 in hyperosmolar hyperglycemic non-ketotic diabetes, 1: 0.24 in type 1
      diabetics, 1: 0.08 in type 2 diabetics, and 1: 0.1 in the control group.
      CONCLUSION: It was concluded that if insulin / glucagon ratio in type 2 diabetics
      reduces to 1: 0.9 then these patients may develop ketoacidosis instead of
      hyperosmolar hyperglycemic non ketotic diabetes. Hence, it is the balance and
      interplay of insulin and glucagon which predicts the type of acute hyperglycemic
      emergencies (diabetic ketoacidosis and hyperosmolar hyperglycemic non-ketotic
      diabetes ) being observed in diabetic patients and not the type of diabetes
      mellitus.

PMID- 16441981
TI  - Hepatitis A virus infection -- shifting epidemiology.
AB  - OBJECTIVE OF THE STUDY: To determine the age distribution in HAV infection and
      seasonal variations in the prevalence of acute viral hepatitis caused by
      hepatitis A virus. STUDY DESIGN: A descriptive study. PLACE AND DURATION: The
      study was carried out on the patients reporting at Virology Department, Armed
      Forces Institute of Pathology (AFIP), Rawalpindi, for determination of hepatitis
      A virus (HAV) IgM antibody, from July 2003 to June 2004. PATIENTS AND METHODS:
      Altogether 626 patients with clinical suspicion of hepatitis A virus infection
      were referred to AFIP Rawalpindi for this test. Blood samples were collected and
      sera were separated and transferred to plastic aliquots that were stored at -20
      degrees C in a retrievable fashion until utilized in testing. The testing for ant
      HAV IgM was carried out with the help of a commercial Enzyme Linked Immunosorbant
      Assay (ELISA) using reagent kits of DiasSorin (Germany) for HAV IgM antibodies.
      RESULTS: The HAV IgM positive rate was 40.57% (252/626). Those tested included
      the sporadic cases as well as the patients from outbreak in two schools of
      Nowshera cantonment. The age of patients testing positive for HAV IgM, ranged
      from 03 to 27 years. There was a statistically significant seasonal difference in
      rate of positivity in different months of the calendar year. An outbreak of HAV
      infection was seen in the children of two neighboring schools of a cantonment, in
      which 44 children in different classes developed clinical jaundice. CONCLUSION:
      HAV infection occurs in a significant proportion of young people with a clinical
      suspicion of HAV infection. There is a changing trend of developing hepatitis A
      in the age beyond 18 years and in outbreaks, which was not there in our patients
      previously due to universal immunity found against HAV by the age of 18. It was
      because of chances of consumption of polluted food.

PMID- 16441982
TI  - Haematological and genetic features of deltabeta-thalassaemia in Pakistan.
AB  - OBJECTIVE: To describe the haematological and genetic features of db-thalassaemia
      in Pakistani patients. DESIGN: Descriptive case series. PLACE AND DURATION OF
      STUDY: Department of Pathology, PNS Shifa, Karachi and Department of Haematology,
      Armed Forces Institute of Pathology, Rawalpindi, from January 1994 to April 2004.
      PATIENTS AND METHODS: Thirteen individuals from six unrelated Pakistani families
      with a haematological diagnosis of deltabeta-thalassaemia were studied. A brief
      clinical history, and the results of blood counts, absolute values, Hb-F, Hb
      A(2), and haemoglobin electrophoresis were recorded. The DNA from each subject
      was first screened for the beta-thalassaemia mutations found in the Pakistani
      population. The samples were then screened for the Inv/Del
      (G)gamma(Agammadelatbeta)(o). RESULTS: The subjects included six heterozygotes,
      six homozygotes and one compound heterozygote of deltabeta- and beta
      thalassaemia. All heterozygotes and 4/6 homozygotes were asymptomatic. One
      homozygote had thalassaemia intermedia while another had transfusion dependent
      anaemia. The mean Hb, TRBC, MCV, MCH, Hb-F and Hb-A(2) in deltabeta-thalassaemia
      heterozygotes were 11.6 g/dl, 5.37 x 10(12)/L, 70.9 fl, and 21.7 pg, 14% and 2.6%
      respectively. The same values in the four untransfused homozygotes were 10.6
      g/dl, 5.34 x 10(12)/L, 69.2 fl, and 20.8 pg, 100% and 0% respectively. The
      mutation analysis revealed that all 13 individuals had the same Inv/Del
      (G)gamma(Agammadeltabeta)(o). CONCLUSION: delatbeta-thalassaemia is a rare
      disorder in Pakistan. Although the clinical picture is very mild its combination
      with beta-thalassaemia trait can produce a sever transfusion dependent
      thalassaemia. The DNA based diagnosis is possible in the prenatal as well as the
      postnatal period.

PMID- 16441983
TI  - Compliance to antihypertensive therapy.
AB  - OBJECTIVE: To determine compliance, factors affecting compliance to
      antihypertensive therapy and to compare compliant and non-compliant groups, in a
      tertiary care setting. STUDY DESIGN: Analytical (cross-sectional) study. PLACE
      AND DURATION OF STUDY: The outpatient clinics at the Aga Khan University from May
      2004 to February 2005. PATIENTS AND METHODS: Two hundred patients presenting to
      the outpatients clinic were included. All patients 18 years and above, who had
      stage 1 and 2 hypertension, had one clinic visit to a medicine clinic, 6 months
      prior to presentation and started on antihypertensive medicines, were included.
      RESULTS: Sixty six percent were males and 33.5 % were females. Mean age was
      58.1(+/-12) years and mean duration of hypertension was 7.2 (+/- 6.7) years.
      Fifty-seven percent were compliant and 43 % were noncompliant. In the
      noncompliant group, 53.4 % had mild noncompliance, 24.4 % had severe non
      compliance, while 22% had moderate noncompliance. Factors of noncompliance were
      56.8% missed doses due to forgetfulness, 12.7% deliberately missed their doses,
      11.6% could not take the medicine due to side effects, 10.4% did not take the
      dose due to increased number of tablets, 4.6% were not properly counseled by the
      physician and 3.48% did not take medicines due to cost issues. The mean systolic
      blood pressure was 126 +/- 19.2 mmHg in the compliant group while it was 133 +/
      16.5 mmHg in the noncompliant group p-value 0.004). The mean diastolic blood
      pressure in the compliant group was 76 +/- 11.9 mmHg, while in the noncompliant
      group it was 81.9 +/-10.9 mmHg (p-value 0.001). CONCLUSION: Compliance to
      antihypertensive therapy in a tertiary care center is significantly good.
      Forgetfulness was the major reason for noncompliance. The mean blood pressure
      control was better in the compliant group.

PMID- 16441984
TI  - Integration of sexual and reproductive health in the medical curriculum in
      Pakistan.
AB  - OBJECTIVE: To assess the knowledge of medical practitioners regarding management
      of selected reproductive tract infections, diagnosis of sexual dysfunction and
      identification of sexual abuse and to assess the attitudes and practices of
      health care providers regarding sexual and reproductive rights in order to
      recommend areas that need to be incorporated in a sexual and reproductive health
      curriculum. DESIGN: A cross-sectional survey. PLACE AND DURATION OF STUDY: From
      March to August 2003 in the District Turbat of Balochistan, Pakistan. SUBJECT AND
      METHODS: Selected indicators of knowledge, attitudes and practices regarding
      sexual and reproductive health of primary care physicians were assessed using a
      pre-tested questionnaire and formal/informal interviews. Variables were
      identified from the literature and previous in-depth interviews, and then
      formulated into respective questions. A Lichert scale marked from 1 to 5 was used
      for categorizing responses into agreed, neutral and disagreed. Descriptive
      statistics were computed using SPSS version 10 for windows. Qualitative
      interviews were translated and transcribed and analyzed according to pre-judged
      and emerging themes. RESULTS: Out of 45 physicians interviewed, nearly half
      scored less than 50% in the knowledge section. Attitudes and practices assessed
      suggested a tendency to be judgmental, gender/rights discriminatory and with
      little provision for enabling clients to make their own decisions, so essential
      for quality sexual health service provision. CONCLUSION: Keeping in view the
      importance of the sexual health issues and a lack of ability of health care
      providers to handle it effectively, deficient areas of sexual health must be
      integrated into the medical curriculum. Medical educators have the responsibility
      to train physicians and other health professionals in the core competencies to
      improve the sexual and reproductive health of their communities.

PMID- 16441985
TI  - Validity of nalidixic acid screening in fluoroquinolone-resistant typhoid
      salmonellae.
AB  - OBJECTIVE: To validate the screening of low-level fluoroquinolone resistance in
      typhoid salmonellae by using nalidixic acid (30 mg) disk providing an acceptable
      zone of inhibition. DESIGN: Quasi-experimental study. PLACE AND DURATION OF
      STUDY: The Department of Microbiology, Armed Forces Institute of Pathology,
      Rawalpindi, Pakistan from July 2002 to June 2003. MATERIALS AND METHODS:
      Antimicrobial susceptibility of 225 clinical isolates of S. typhi (n=126) and S.
      paratyphi A (n=99) against nalidixic acid and ciprofloxacin was determined by the
      modified Kirby-Bauer disk diffusion and agar dilution techniques of NCCLS. The
      relationship between the zone sizes and the MICs of the two quinolones was
      plotted in the form of scattergrams and nalidixic acid MICs and zone of
      inhibition sizes were correlated with those of ciprofloxacin by regression
      analysis. RESULTS: One hundred and ninety-five isolates were nalidixic acid
      susceptible (MIC <16 microg/mL) and approximately 30 were nalidixic acid
      resistant (MIC >32 microg/mL). All the nalidixic acid-susceptible isolates had
      ciprofloxacin MIC of <0.064 microg/mL. Among the nalidixic acid-resistant
      isolates approximately 20 had ciprofloxacin MIC > or =0.125 microg/mL and
      approximately 10 had ciprofloxacin MIC < or =0.03-0.064 microg/mL. The diameter
      of inhibition zone around a 30 mg nalidixic acid disk of nalidixic acid-resistant
      isolates was < or =13 mm (range 6-16 mm, mean 10.3 mm + SD 3.5 mm), while among
      nalidixic acid-susceptible isolates it ranged from 14 to 30 mm (mean 23.8 mm + SD
      2.2 mm). The diameter of inhibition zone around a 5mg ciprofloxacin disk of
      nalidixic acid-resistant isolates ranged from 26 to 35 mm (mean 29.8 mm + SD 3.1
      mm), while in nalidixic acid-susceptible isolates it ranged from 32 to 42 mm
      (mean 36.6 mm + SD 1.9 mm). With ciprofloxacin MIC > or =0.125 microg/mL taken as
      a breakpoint, a zone of <or =33 mm around a 5 microg ciprofloxacin disk to detect
      low susceptibility strains had a sensitivity of 100% and a specificity of 82%.
      Screening for nalidixic acid resistance (inhibition zone diameter of < or =13 mm)
      in isolates with ciprofloxacin MIC 0.125 microg/mL using a 30 microg nalidixic
      acid disk yielded a sensitivity of 100% and a specificity of 95%. CONCLUSION:
      Screening for nalidixic acid resistance with a 30 microg nalidixic acid disk is a
      reliable and cost-effective method for detection of low-level fluoroquinolone
      resistance in typhoid salmonellae.

PMID- 16441986
TI  - Levamisole in steroid dependent and frequently relapsing nephrotic syndrome.
AB  - OBJECTIVE: To determine the efficacy of levamisole in steroid dependent (S.D) and
      frequently relapsing (F.R) nephrotic, from syndrome (N.S). DESIGN: Quasi
      experimental study. PLACE AND DURATION OF STUDY: Department of Nephrology at The
      Children s Hospital, Lahore, over a period of 5 years from January 2000 to
      December 2004. MATERIAL AND METHODS: S.D.N.S and F.R.N.S patients between the
      ages of 1-15 years, were given levamisole on alternate day in a dose of 2.5
      mg/kg, if either the dosage of steroids to maintain remission was >1 mg/kg/every
      other day (EOD), or 0.5 mg/kg/EOD with signs of steroid toxicity. The agent was
      continued for a period of one year and the steroids were gradually tapered off by
      2.5-5 mg every four weeks to less than 0.5 mg/kg/EOD. The patients were monitored
      for maintenance of remission and side effects of drug. RESULTS: Seventy patients
      with a mean age of 5.50+/-2.97 years , with male to female ratio of 4:1 were
      studied. Nineteen (27.14%) patients did not relapse on therapy, while it was
      ineffective in 11(15.7%). Rest of 40 (57.14%) patients, though, relapsed during
      therapy, their duration of remission was prolonged from six months to one year,
      and dose of corticosteroids could be significantly reduced (0.1-0.3 mg/kg/EOD).
      It was also observed that levamisole is more effective in older children (>5
      years versus <5 years) [P-value 0.03]. The only side effects were transient rash
      and occasional vomiting. CONCLUSION: Levamisole is a safe and effective steroid
      sparing drug, in steroid dependent and frequently relapsing nephrotic syndrome,
      for the prolongation of remission, especially in older children.

PMID- 16441987
TI  - Proptosis: etiology and demographic patterns.
AB  - OBJECTIVE: To determine the demographic pattern of patients presenting with
      proptosis and its etiology. DESIGN: A cross-sectional descriptive study. PLACE
      AND DURATION OF STUDY: Khyber Institute of Ophthalmic Medical Sciences (KIOMS),
      Hayatabad Medical Complex, Peshawar from July 2001- December 2002. PATIENTS AND
      METHODS: Sixty cases of proptosis presenting at KIOMS were included. Thirtysix
      patients were male while 24 were female. They were divided into two age groups; 0
      15 years (paediatric group) and above 15 years (adult group). An elaborate work
      up plan was formulated for all patients, which included detailed history,
      clinical examination (ocular, orbital and systemic), radiological and
      histopathological investigations. RESULTS: Neoplasms (33%) were the most common
      causes of proptosis in all the patients followed by orbital inflammations (23%),
      orbital infections (20%), structural abnormalities (12%), vascular abnormalities
      (7%) and trauma (5%). CONCLUSION: Neoplasms were the most common cause of
      proptosis in both paediatric and adult group. Proptosis was the cardinal feature
      and visual deterioration was present in more than half of the patients. Timely
      referral, early diagnosis and appropriate management can result in reduction of
      visual morbidity.

PMID- 16441988
TI  - Intralesional corticosteroid injection vs surgical treatment of chalazia in
      pigmented patients.
AB  - OBJECTIVE: To compare the outcome of intralesional corticosteroid injection and
      surgical treatment of chalazia. DESIGN: An interventional comparative study.
      PLACE AND DURATION OF STUDY: PNS Shifa, Naval Hospital, Karachi from 1st
      September 2002 to 31st August 2003. PATIENTS AND METHODS: During a 9-month
      recruitment period all patients attending PNS Shifa, Naval Hospital, Karachi, for
      treatment of chalazia were inducted in the study. A 141 patients with chalazia
      completed the study. Patients received either incision-curettage (surgical
      treatment/ ST group) or intralesional corticosteroid injection treatment (steroid
      injection/ SI group). The same procedure was repeated in unsuccessful cases only
      once. Z-test of proportion was used as appropriate statistical test of
      significance at p <0.05 for the comparison of the results between the two groups.
      RESULTS: The success was achieved in 59 out of 75 patients (79%) in ST group and
      41 of 66 patients (62%) in SI group at first visit after two weeks (p-value
      <0.01). The success in ST group improved to 89% (67 out of 75 patients) after
      second operation and to 80% (53 out of 66 patients) in SI group after second
      injection of the steroid given at second week (p-value < 0.14). CONCLUSION:
      Intralesional steroid injection is an effective and safe alternative procedure
      for the treatment of chalazia. The results are comparable to surgical treatment
      especially after second injection. It is not associated with any serious
      complications although skin depigmentation is relatively common in coloured
      population.

PMID- 16441989
TI  - Role of single dose antibiotic prophylaxis in clean orthopedic surgery.
AB  - OBJECTIVE: To compare the proportion of early postoperative infection in clean
      orthopedic surgery after single dose of prophylactic antibiotic and multiple
      doses of prophylactic antibiotic. DESIGN: Interventional quasi-experimental
      study. PLACE AND DURATION OF STUDY: Department of Orthopedics, Abbasi Shaheed
      Hospital, Karachi from April 2004 to March 2005. MATERIAL AND METHODS: Two
      hundred patients of either age and gender, undergoing clean orthopedic surgery
      were equally divided into two groups A and B. Group A was given single dose of
      prophylactic antibiotic, while group B was given multiple doses of prophylactic
      antibiotic. Follow-up period was 28 days. All cases were evaluated for
      postoperative wound infection. Sampling technique was non-probability
      convenience. RESULTS: Mean age was 35.51+/-20.79 years in group A and 26.17+/
      19.79 years in group B. However, there was a significantly higher proportion of
      male patients in group B than in group A (p=0.006). Statistical analysis showed
      no significant difference in the proportion of early postoperative infection
      cases between the two groups(p=0.270). Staphylococcus aureus was the commonest
      organism cultured from the wound discharge in our study followed by E. coli.
      Eight of our cases having postoperative wound infection showed no growth, out of
      which 7 were superficial and 1 was deep. There was no significant difference
      between the two groups regarding mean operating time and duration of stay in
      hospital. CONCLUSION: There was no statistically significant difference in the
      proportion of early postoperative infection cases between the two groups.

PMID- 16441991
TI  - Gift authorship.

PMID- 16441990
TI  - Estimation of ionized calcium, total calcium and albumin corrected calcium for
      the diagnosis of hypercalcaemia of malignancy.
AB  - OBJECTIVE: To measure levels of ionized calcium, total calcium and albumin
      corrected calcium in patients with different malignant disorders for the
      diagnosis of hypercalcaemia of malignancy. DESIGN: A case control comparative
      study. PLACE AND DURATION OF STUDY: The study was carried out in the Department
      of Pathology, Army Medical College Rawalpindi, Armed Forces Institute of
      Pathology and Department of Oncology CMH, Rawalpindi from March 2003 to December
      2003. SUBJECTS AND METHODS: Ninetyseven patients of various malignant disorders,
      admitted in the Department of Oncology, CMH, Rawalpindi, and 39 age and gender
      matched disease-free persons (as control) were included in the study. Blood
      ionized calcium (Ca++), pH, sodium (Na+) and potassium (K+) were analysed by Ion
      selective electrode (ISE) on Easylyte auto analyser. Other related parameters
      were measured by colourimetric methods. RESULTS: Blood Ca(++) levels in patients
      suffering from malignant disorders were found significantly high (mean +/- SD:
      1.30+017 mmol/L) as compared to control subjects (mean +/- SD 1.23+0.03 mmol/L)
      (p<0.001). The number of patients with hypercalcaemia of malignancy detected by
      Ca(++) estimation was significantly higher (38%) as compared to total calcium
      (8.4%) and albumin corrected calcium ACC (10.6%) (p<0.001). There was no
      statistically significant difference in other parameters e.g. phosphate, urea,
      creatinine, pH, Na+ and K+ levels in study subjects and controls. CONCLUSION:
      Detection of hypercalcaemia can be markedly improved if ionized calcium
      estimation is used in patients with malignant disorders.

PMID- 16441992
TI  - Role of testicular interleukin-1alpha tIL-1alpha in testicular physiology and
      disease.
AB  - This review focuses on the role of the cytokine interleukin-1alpha (IL-1alpha) in
      the testis; elaborating upon its importance during the complex process of
      spermatogenesis while relating this cytokine to some of the pathophysiological
      states affecting the testis. IL-1alpha, a proinflammatory cytokine, is expressed
      constitutively by the intact adult rat testis where it acts on germ, Sertoli and
      Leydig cells to regulate germ cell proliferation and steroidogenesis. The
      sequence identity of testicular IL-1alpha matches with the one secreted by
      activated macrophages in systemic immunity. The classical macrophage IL-1alpha is
      produced as 32 kDa precursor protein which is processed to mature 17 kDa IL
      1alpha and a 16 kDa propiece. The rat testicular IL-1alpha, mainly secreted by
      Sertoli cells, was found to have molecular heterogeneity that can be observed
      both at the transcriptional and the translational levels. In the rat testis, two
      transcripts were found to be expressed with 941 bp and 767 bp (that lacks 174 bp)
      which were translated into 32 kDa and 24 kDa precursor proteins, respectively.
      The 32 kDa precursor protein is processed to the 17 kDa mature IL-1alpha.
      Identical transcripts are also shown to be present in cat, dog and pig. Most of
      the functional role is assigned to the mature 17 kDa IL-1alpha isoform. However,
      functional analysis of recombinant rat IL-1alpha isoforms showed that there was a
      clear biopotency difference between these forms in order of 17 kDa IL
      1alpha>32proIL-1alpha>24proIL-1alpha. Furthermore, the mature 17 kDa tIL-1alpha
      has also been implicated in pathologies such as orchitis, relapse of acute
      lymphoblastic leukemia (ALL) in the testis and infertility disorders in men.
      Thus, tIL-1alpha may play an important functional role both in coordination of
      normal testicular physiology as well as in contributing to the disease states in
      the testis.

PMID- 16441994
TI  - Pelvic tuberculosis mimicking malignant ovarian tumour.
AB  - Two cases of pelvic tuberculosis with markedly raised serum CA 125 levels and
      initially suspected of ovarian carcinoma are presented. Tuberculosis is highly
      prevalent in developing world and should be considered in the diagnosis of pelvic
      mass, ascites and elevated serum CA 125 levels.

PMID- 16441995
TI  - In-vivo purging with the anti-CD20 antibody rituximab along with standard
      allogeneic peripheral blood stem cell transplantation (PBSCT) for relapsed
      childhood pre-B acute lymphoblastic leukaemia (ALL).
AB  - This case report describes the use of Rituximab for in vivo purging (by
      intravenous infusion) in a 12 years old boy with second remission of pre-B ALL.
      It was followed by conditioning therapy consisted of Busulphan and
      Cyclophosphamide. rh-G-CSF primed stem cells from an HLA identical sibling donor
      were infused. Standard graft versus host disease prophylaxis was given. He
      engrafted within two weeks. He did not develop acute graft versus host disease
      (aGvHD) but localized chronic GvHD developed. He had been on regular follow-up at
      CMH, Rawalpindi and is in complete remission 13 months post-PBSCT with no
      evidence of chronic GvHD at present.

PMID- 16441993
TI  - Hypohidrotic ectodermal dysplasia (HED).
AB  - Hypohidrotic Ectodermal Dysplasia (HED) is a hereditary congenital disorder of
      ectodermal origin. It is characterized by lack of sweat glands (hypohidrosis),
      nail dystrophy(onychodysplasia), alopecia (hypotrichosis), defective palms and
      soles (palmoplantar hyperkeratosis) and the oral presentations of partial absence
      of teeth (hypodontia) or complete absence of teeth (anodontia). Hypodontia of
      primary and permanent dentition is one of the most frequently occurring oral
      symptoms in HED patients. These features of poor aesthetic affect the social and
      the psychological well-being of the patient. This case report describes the
      prosthetic rehabilitation of a HED patient.

PMID- 16441996
TI  - Bilateral diffuse tuberculosis of the parotid gland.
AB  - Tuberculosis of the parotid gland is an unusual occurrence. We describe here a
      case of bilateral parotid gland tuberculosis showing diffuse involvement, which
      is even more rare. The patient was diagnosed on fine needle aspiration cytology
      and treated with WHO-approved Directly Observed Treatment Short Course (DOTS)
      category III regimen under Revised National Tuberculosis Programme with effective
      remission.

PMID- 16441997
TI  - Pulmonary embolism at high altitude and hyperhomocysteinemia.
AB  - This case report describes pulmonary embolism in a patient as a complication of
      extended stay at high altitude. He also had increased plasma homocysteine levels.
      Hypercoagulability at high altitude along with hyperhomocysteinemia is a risk
      factor for arterial and venous thrombosis.

PMID- 16441998
TI  - Castleman's disease -- a rare disease of lymph nodes.
AB  - Castleman's disease is a rare disorder of unknown etiology and different clinical
      manifestations, occurring in young adults (usually prior to age 30 years). In
      this case report we present one such case who was a 16 years old male with
      abdominal pain, weight loss, cervical lymph adenopathy and hepatosplenomegaly.
      Lymph node biopsy revealed hyaline-vascular type of Castleman's disease. He was
      put on chemotherapy but was lost to follow-up.

PMID- 16441999
TI  - Laparoscopic adrenalectomy for Conn's syndrome.
AB  - Laparoscopic adrenalectomy is now used worldwide to resect adrenal adenomas and
      other adrenal tumors recently introduced in Pakistan. Two cases of endocrine
      hypertension, due to Conn s syndrome, undergoing laparoscopic adrenalectomy for
      the first time here, are reported.

PMID- 16442000
TI  - Primary malignant lymphoma of the appendix associated with acute appendicitis.
AB  - Malignant lymphoma comprises 1-4% of the malignant neoplasm of the
      gastrointestinal tract. Appendiceal lymphomas are extremely rare, reported in
      0.015 percent of all gastrointestinal lymphomas. This is a report of a case of
      localized malignant lymphoma of the appendix associated with the histological
      features of acute inflammation that presented clinically as acute appendicitis. A
      three years follow-up after appendectomy alone did not show any evidence of
      recurrent disease. This case report emphasizes the importance of routine
      histology examination of the appendectomy specimen.

PMID- 16442001
TI  - Paraneoplastic syndrome of renal cell carcinoma.
AB  - We report a case of renal cell carcinoma who presented with the classic triad of
      flank pain, hematuria and fever as well as progressively developed multisystem
      disease, including a massive anteroseptal myocardial infarction. This was
      diagnosed as paraneoplastic syndrome of renal cell carcinoma and the decision to
      proceed with nephrectomy was taken after 3 weeks of acute myocardial infarction,
      despite predicted high cardiac risk under general anaesthesia; following removal
      of tumour, all symptoms and signs regressed. He has remained well till the time
      of last follow-up 4 months later.

PMID- 16442003
TI  - A starting point for medical students.

PMID- 16442002
TI  - Cholecystoduodenal fistula secondary to penetrating duodenal ulcer: a case of
      conservative management.

PMID- 16442013
TI  - Measurement variability of the lateral head-shaft angle in slipped capital
      femoral epiphysis.
AB  - The lateral head-shaft angle as described by Southwick is used to assess the
      severity of slipped capital femoral epiphysis and to measure progression.
      Intraobserver variability in measuring the lateral head-shaft angle may influence
      decision making. The purpose of this study was to determine intraobserver
      variability in the measurement of the lateral head-shaft angle of slipped capital
      femoral epiphysis. The lateral head-shaft angle of 108 hips was measured twice by
      three observers. The two-way analysis of variance method of Bland and Altman as
      outlined by Loder was used to determine the intraobserver variability. For the
      lateral head-shaft angle in slipped capital femoral epiphysis, the intraobserver
      variability was +/-5.9 degrees . To ensure true change, a single observer should
      document at least a 12 degrees change in the lateral head-shaft angle between two
      radiographs.

PMID- 16442015
TI  - A cadaveric study comparing standard fluoroscopy with fluoroscopy-based computer
      navigation for screw fixation of the odontoid.
AB  - Although direct osteosynthesis of certain types of odontoid fractures may
      increase union and decrease the need for prolonged immobilization, screw fixation
      remains a technically demanding procedure. This study compares radiation
      exposure, surgical time, and accuracy of hardware placement using standard
      fluoroscopy versus computer-assisted fluoroscopy-based navigation ("virtual
      fluoroscopy") to assist with the placement of odontoid screws. Twenty-two
      cadavers were divided into two groups and underwent placement of a single
      odontoid screw using either standard fluoroscopic or virtual fluoroscopic
      guidance. Following screw placement, dissection of the C1-C2 segments was
      performed to assess accuracy. A significant reduction in fluoroscopy time was
      noted with the computer-based fluoroscopy technique, whereas the surgical time
      was not found to differ significantly between the techniques. No critical
      breaches (those risking neurovascular injury) were noted in either group, and the
      rate of noncritical breaches did not differ. The authors conclude that
      fluoroscopy-based virtual navigation appears to have a safety profile similar to
      standard fluoroscopy while allowing a reduction in radiation exposure.

PMID- 16442014
TI  - Malignant peripheral nerve sheath tumors: an update.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant cancers
      that account for approximately 5-10% of all soft tissue sarcomas. They occur
      either sporadically, in association with neurofibromatosis type 1 (NF1), or
      subsequent to radiation therapy. Histologically, MPNSTs resemble fibrosarcomas in
      their basic organization. Immunohistochemistry, particularly S100, plays an
      important role in the diagnosis. At the molecular level, loss of the NF1 gene and
      high levels of Ras-activity are hallmarks. Magnetic resonance imaging (MRI) is
      the most helpful imaging technique to clearly identify tumoral extent and to
      suggest neurogenic origin. The presence of heterogeneity with evidence of
      necrosis and hemorrhage on MRI and increased uptake on positron emission
      tomography scan may prove helpful in detecting malignant changes. MPNSTs need to
      be approached by a multidisciplinary team, assuring the complete surgical removal
      of the lesion. Disease-free and overall survival statistics reinforce the
      aggressive nature of this unique soft tissue tumor.

PMID- 16442016
TI  - Upper extremity dog bite wounds and infections.
AB  - Upper extremity dog bite wounds comprise a large percentage of all mammalian bite
      wounds. The purpose of the study was to assess the bacteriology of patients
      presenting with such injuries to the emergency room that required consultation by
      a hand surgeon. The study also analyzed the effect of delayed intervention on
      growth of invasive pathogens, on the incidence of multiple pathogens, on
      treatment interventions, and on length of hospital stay. Objective data and
      subjective descriptions of the wound were collected on 32 patients who presented
      to Chicago area hospitals. The authors retrospectively analyzed the data and
      grouped the patients into two categories based on time of intervention: early or
      those treated within 48 hours, and delayed to include those treated after 48
      hours. Incidence of bacterial growth and Pasteurella species growth in cultures
      was similar to that reported in the literature. Delayed patients had a
      significantly higher incidence of positive bacterial growth from wound cultures
      (100%) compared with nondelayed patients (54%). Delayed patients also had a
      higher incidence of treatment intervention (delayed group 86% surgical irrigation
      and debridement compared with 48% for the early group). There was a trend toward
      increased length of hospital stay (delayed group 4.6 days compared with 2.6
      days), although this was not significant. The growth of multiple pathogens
      between the two groups was similar and not significant (delayed group 43%
      compared with 54% early group).

PMID- 16442017
TI  - Acute hip arthroplasty for the treatment of intertrochanteric fractures in the
      elderly.
AB  - Arthroplasty for intertrochanteric fractures in elderly patients may allow early
      weightbearing and avoid fixation failure. Clinical results are reviewed in a
      consecutive group of acute arthroplasties (5 hemiarthroplasties and 29 total hip
      arthroplasties) performed via the anterolateral approach for intertrochanteric
      fractures. Age averaged 80.2 years. Follow-up averaged 35 months for living
      patients. Twenty-six patients died during follow-up. Time to death averaged 3.5
      years. Five hips, all total hip arthroplasties, required subsequent surgeries:
      four for dislocation and one revised for sepsis. Acute intertrochanteric
      fractures are associated with high early mortality. In this series, a 15%
      complication rate and high mortality rate at 12 years was associated with acute
      arthroplasty. Dislocation is higher than in primary total hip arthroplasty
      utilizing the same surgical approach. The results do not support routine use of
      arthroplasty in treatment of intertrochanteric hip fractures in the elderly.

PMID- 16442018
TI  - Acute sepsis complicating degenerative arthritis of the hip joint: a report of
      three cases.
AB  - This case report involves three patients in whom hip sepsis occurred in
      association with degenerative joint disease, in the absence of any risk factors
      for infection. The diagnosis had been missed on initial evaluation, and each
      patient had been referred to the authors' adult reconstructive service to have
      the arthritic hip replaced. In each instance, existing hip pain had worsened
      acutely. Further workup led to the correct diagnosis and appropriate treatment of
      the septic joint. These cases illustrate the value of differential diagnosis when
      treating patients with degenerative hip disease.

PMID- 16442019
TI  - Minimally invasive hallux valgus correction: a technical note and a feasibility
      study.
AB  - Hallux valgus surgery aims to correct the nonphysiological angulation of the
      first ray and rebalance its function. Many techniques are reported, each with
      different indications depending on the pathoanatomy of the deformity. This
      article presents a minimally invasive distal metatarsal osteotomy technique,
      requiring no custom instrumentation. The operation is performed under direct
      vision and without fluoroscopy.

PMID- 16442020
TI  - Re: Delayed presentation of ipsilateral femoral neck fractures in diaphyseal
      femur fractures, Gibson W.K., Hubbard J., JSOA 14(2): 77-81, 2005.

PMID- 16442022
TI  - Stage I and II posterior tibial tendon dysfunction treated by a structured
      nonoperative management protocol: an orthosis and exercise program.
AB  - BACKGROUND: Posterior tibial tendon dysfunction (PTTD) is a relatively common
      problem of middle-aged adults that usually is treated operatively. The purpose of
      this study was to identify strength deficits with early stage PTTD and to assess
      the efficacy of a focused nonoperative treatment protocol. METHODS: Forty-seven
      consecutive patients with stage I or II posterior tibial tendon dysfunction were
      treated by a structured nonoperative protocol. Criteria for inclusion were the
      presence of a palpable and painful posterior tibial tendon, with or without
      swelling and 2) movement of the tendon with passive and active nonweightbearing
      clinical examination. The rehabilitation protocol included the use of a short,
      articulated ankle foot orthosis or foot orthosis, high-repetition exercises,
      aggressive plantarflexion activities, and an aggressive high-repetition home
      exercise program that included gastrocsoleus tendon stretching. Isokinetic
      evaluations were done before and after therapy to compare inversion, eversion,
      plantarflexion, and dorsiflexion strength in the involved and uninvolved
      extremities. Criteria for successful rehabilitation were no more than 10%
      strength deficit, ability to perform 50 single-support heel rises with minimal or
      no pain, ability to ambulate 100 feet on the toes with minimal or no pain, and
      ability to tolerate 200 repetitions of the home exercises for each muscle group.
      RESULTS: Before therapy weakness for concentric and eccentric contractures of all
      muscle groups of the involved ankle was significant (p<0.001). After a median of
      10 physical therapy visits over a median period of 4 months, 39 (83%) of the 47
      patients had successful subjective and functional outcomes, and 42 patients (89%)
      were satisfied. Five patients (11%) required surgery after failure of
      nonoperative treatment. CONCLUSION: This study suggests that many patients with
      stage I and II posterior tibial tendon dysfunction can be effectively treated
      nonoperatively with an orthosis and structured exercises.

PMID- 16442023
TI  - A surgical approach for flexible flatfeet in adults including a subtalar
      arthroereisis with the MBA sinus tarsi implant.
AB  - BACKGROUND: The purpose of this study was to determine the functional outcomes
      and radiographic results of adult patients who had an operation for flexible
      flatfeet without any hindfoot osteotomies or fusions. METHODS: Twenty-eight feet
      in 23 patients with problems caused by their flexible flatfoot deformities had
      reconstructive foot and ankle surgery that included a subtalar arthroereisis (the
      restriction of the range of motion of a joint) with the Maxwell-Brancheau
      Arthroereisis (MBA) sinus tarsi implant. The American Orthopedic Foot and Ankle
      Society (AOFAS) Hindfoot Scale and a patient assessment questionnaire were
      obtained from all patients before surgery and at final follow-up. Preoperative
      and postoperative standing radiographs were analyzed to determine radiographic
      correction of the deformities. The average followup was 44 months. The MBA
      implant was surgically removed in 11 of 28 feet (39%) because of sinus tarsi
      pain. RESULTS: The average preoperative AOFAS score was 52 and had improved to 87
      (p<0.00001) at final followup. The average response to four of five questions in
      the patient assessment had significantly improved (p<0.05). On a 10-point scale,
      average patient satisfaction was 8.3 points; 78% said that they would have the
      surgery again. Correction after surgery was significant (p<0.0001) in each of the
      three radiographic parameters evaluated for 'correction with MBA' and 'final
      correction.' With the numbers available, no significant differences could be
      detected after the MBA was removed. Complications included sinus tarsi pain in
      46% (13) of the 28 feet in this study; after implant removal, 73% (8) of 11 feet
      had less discomfort than before surgery with AOFAS scores 80 or better.
      CONCLUSIONS: Reconstructive foot and ankle surgery that included a subtalar
      arthroereisis with the MBA sinus tarsi implant resulted in favorable clinical
      outcomes and patient satisfaction in 78% (18) of 23 patients. In spite of the
      high incidence of temporary sinus tarsi pain until the implant was removed, this
      operative approach compares favorably with other operations for flexible flatfoot
      deformities in adults.

PMID- 16442024
TI  - Coralline hydroxyapatite bone graft substitute in hindfoot surgery.
AB  - BACKGROUND: Coralline hydroxyapatite bone graft substitute material is created by
      the conversion of the calcium carbonate structure of coral into hydroxyapatite.
      The microstructure of the material resembles cancellous bone and provides an
      osteoconductive scaffold for bone ingrowth. The use of this material is reported
      in the orthopedic oncology and trauma literature. Short-term reports in foot
      procedures have been reported. METHOD: A retrospective review identified 10
      patients who had undergone hindfoot arthrodesis with coralline hydroxyapatite
      bone graft. The charts were reviewed for outcomes, operative complications, and
      time to union. Nine of the 10 patients were available for additional examination.
      RESULTS: The average followup was 6 years. There were three complications. One
      patient had sural nerve numbness with partial resolution which was unrelated to
      the graft material. A rheumatoid patient on methotrexate and prednisone developed
      a deep wound infection 9 months after surgery. One patient had a nonunion of the
      talonavicular joint. Eight of the 10 patients reported good or excellent results.
      Radiographs continued to demonstrate the presence of the graft material at 6
      years. Radiographs showed extrusion of the graft from the joint in all patients.
      No patient had symptoms from the extruded material. DISCUSSION: Coralline
      hydroxyapatite bone graft substitute appears to be a clinically effective
      material for use in foot procedures. No adverse events could be linked to the
      graft material. The graft material is difficult to contain and extrusion was
      present in all patients. The slow resorption is a concerning characteristic of
      the graft material. At 6-year followup, the continued presence of the material
      has not shown any adverse effect.

PMID- 16442025
TI  - Radiographic indicators of ankle instability: changes with plantarflexion.
AB  - BACKGROUND: The effect of plantarflexion on radiographic indicators of
      instability was investigated in matched pairs of stable ankles and unstable ankle
      fractures with complete deltoid ligament tears to test the hypothesis that
      differences exist in indicators as a function of either stability or position.
      The purpose of this study was to determine whether plantarflexion increases
      radiographic indicators of ankle fracture instability. METHODS: Measurements from
      34 patients scheduled for operative treatment of unstable ankle fractures were
      collected prospectively from normal, stable ankles and the injured, unstable
      ankles. Instability was defined as a positive fluoroscopic stress examination
      under anesthesia. Stability and instability and neutral position and
      plantarflexion were associated with eight radiographic indicators of which five
      were distances in millimeters and three were binomial (either stable or
      unstable). RESULTS: Measurements were larger in the unstable ankles than in the
      normal stable ankles. Plantarflexion was associated with increased distances in
      stable ankles, and a trend was seen in unstable ankles. Plantarflexion was
      associated with increased binomial indicators in unstable ankles but not in
      stable ankles. DISCUSSION: Joint positioning affected measurement of ankle
      stability: plantarflexion increased the sensitivity of radiographic indicators.

PMID- 16442026
TI  - Clinical and radiographic features of operatively treated stiff clubfeet after
      skeletal maturity: etiology of the deformities and how to prevent them.
AB  - BACKGROUND: Residual deformities of operatively treated severe clubfeet evaluated
      radiographically have been rarely studied in detail in adults. METHODS: Twenty
      five operatively treated stiff clubfeet were analyzed at a mean age of 21 years
      and 6 months. The clinical evaluation used the Laaveg and Ponseti scale for
      clubfeet. Radiographic assessment was done with weightbearing and dynamic views.
      RESULTS: Clinical evaluation was globally good except for motion (poor).
      Radiographic assessment showed residual abnormalities in all feet. The distal
      tibial epiphysis showed slanting of its posterior part in seven feet (28%) and
      notching of its anterior lip in 13 (52%). Talar length, calcaneal length, and
      talar trochlear height were significantly smaller in clubfeet compared to normal
      feet. Undercorrection of hindfoot varus, was found in 19 feet (76%) but was well
      tolerated. Navicular wedging was present in seven (28%), and cavus deformity was
      found in seven (28%). Dorsal bunion, hallux varus, and skewfoot were found in
      four (16%), two (8%), and three (12%), respectively. The dynamic views
      demonstrated a significant decrease in the foot and ankle mobility with
      compensation mechanisms such as anterior talar incongruence or midfoot
      hypermobility. CONCLUSION: Severe clubfeet never become normal at adult age
      either clinically or radiographically. Multiple radiographic deformities exist.
      Their etiology and possible prevention are discussed. Despite the numerous
      abnormalities, clinical results were good at skeletal maturity.

PMID- 16442027
TI  - Evaluation of the validity of the Foot Function Index in measuring outcomes in
      patients with foot and ankle disorders.
AB  - BACKGROUND: There is uncertainty regarding which outcomes tools should be used to
      report the results of treatment for patients with foot and ankle disorders. This
      study evaluates the validity of the Foot Function Index (FFI) by examining its
      level of correlation to the Medical Outcomes Study Short Form-36 (SF-36). The SF
      36 is an extensively validated outcomes tool that has been used as a benchmark in
      examining the validity of several orthopaedic outcomes tools. METHODS: Seventy
      three patients were recruited at a tertiary referral foot and ankle practice.
      Patients completed packets which included informed consent forms, the FFI, and
      the SF-36 questionnaires. The questionnaires were scored and Pearson correlation
      coefficients were determined between the three domains of the FFI and the eight
      SF-36 sub-scales, as well as the two SF-36 summary scales. RESULTS: Sixty-nine
      patients completed an adequate number of items to be included in the study. The
      mean age of the patient sample was 46 (range 16 to 82) years and 44 were women
      (64%). Twenty-one patients (30%) had conditions affecting the forefoot, while 48
      patients (70%) had conditions affecting the ankle or hindfoot. All three FFI
      domains had moderate to high levels of correlation to many of the SF-36 scales.
      The Disability domain of the FFI had the most consistent level of correlation to
      the SF-36 with Pearson coefficients in the range of -0.23 to -0.69. The Activity
      Limitation (r=-0.28 to -0.64) and Pain domains (r=-0.10 to -0.61) also
      demonstrated moderate levels of correlation to several of the SF-36 scales.
      CONCLUSIONS: The consistently moderate to high levels of correlation of the FFI
      to the SF-36 seen in this study support the FFI as a valid measure of health
      status. This suggests that the FFI is a reasonable method to monitor patient
      outcomes. Future studies should focus on determining if the FFI improves
      responsiveness to clinical change when used in combination with generic
      instruments like the SF-36.

PMID- 16442028
TI  - The effect of triceps surae contracture force on plantar foot pressure
      distribution.
AB  - BACKGROUND: Triceps surae contractures have been associated with foot and ankle
      pathology. Achilles tendon contractures have been shown to shift plantar foot
      pressure from the heel to the forefoot. The purpose of this study was to
      determine whether isolated gastrocnemius contractures had similar effects and to
      assess the effects of gastrocnemius or soleus contracture on midfoot plantar
      pressure. METHODS: Ten fresh frozen cadaver below-knee specimens were loaded to
      79 pounds (350 N) plantar force with the foot unconstrained on a 10-degree
      dorsiflexed plate. Combinations of static gastrocnemius or soleus forces were
      applied in 3-lb increments and plantar pressure recordings were obtained for the
      hindfoot, midfoot, and forefoot regions. RESULTS: The percentage of plantar force
      borne by the forefoot and midfoot increased with triceps surae force, while that
      borne by the hindfoot decreased (p<or=0.005). Increasing gastrocnemius force had
      similar results. Increasing triceps surae force from 0 to 21 lbs (93 N) increased
      average percent forefoot and midfoot force 59% and 38%, respectively, and reduced
      average percent hindfoot force 18%. Increasing gastrocnemius force from 0 to 18
      lbs increased average percent forefoot and midfoot force 50% and 32%,
      respectively, and reduced average percent hindfoot force 16%. For a given triceps
      surae force, there was no statistical difference in pressure distribution noted
      between different combinations of gastrocnemius and soleus force. CONCLUSIONS: In
      a static model, increased triceps surae or isolated gastrocnemius force shifted
      weightbearing plantar pressure from the hindfoot to the midfoot and forefoot.
      Similar results were noted whether the triceps surae force was applied through
      the gastrocnemius or soleus or both. The results of this study are consistent
      with the clinical association of triceps surae contracture with foot and ankle
      disorders including diabetic foot ulcers and metatarsalgia. The similar effects
      with triceps surae force application through the gastrocnemius or soleus suggest
      that patients with isolated gastrocnemius contractures may obtain similar
      clinical benefits with potentially less morbidity after gastrocnemius aponeurosis
      lengthening as compared to Achilles tendon lengthening.

PMID- 16442029
TI  - An analysis of talar surface area occupied by screw fixation in ankle fusions.
AB  - BACKGROUND: Ankle arthrodesis remains the benchmark of treatment for end-stage
      arthrosis of the ankle joint. Despite that, the incidence of nonunion can be as
      high as 15%. Various strategies have been used to reduce the incidence of
      nonunion, including multiple compression screws and larger diameter screws to
      improve mechanical stability and compression. The space occupied by an increasing
      amount of hardware across a finite surface area available for fusion has prompted
      concern that this strategy may be counterproductive and may reduce the biological
      potential of the construct. The purpose of this study was to look at 40 anatomic
      sawbone specimens of the ankle to determine the amount of talar surface contact
      area used by the screw fixation during arthrodesis. METHODS: Four groups were
      created to examine different techniques for arthrodesis. Simulated ankle
      arthrodeses were done using two- or three-screw fixation with 6.5-mm and 7.3-mm
      screws. Hardware was subsequently removed and the surface area used by the
      passing screws was measured. Total surface areas were calculated for each of the
      40 specimens. RESULTS: The maximal surface area of the talus occupied by screws
      occurred when using three 7.3-mm screws. This configuration used 16% of the
      possible talar surface area available for arthrodesis. CONCLUSION: The use of
      additional screw fixation when performing an ankle arthrodesis does not sacrifice
      a major amount of the tibiotalar contact area and will most likely not affect the
      biologic environment needed to obtain fusion.

PMID- 16442030
TI  - Reconstruction of the soft tissue of the heel with artificial dermis and
      recombinant basic fibroblast growth factor: case report.

PMID- 16442031
TI  - Management of a flail foot in cauda equina syndrome by neoligament tenodesis: a
      case report.

PMID- 16442032
TI  - Technique tip: bivalving a below knee cast with a stable notch.

PMID- 16442033
TI  - Current concept review: acquired adult flatfoot deformity.

PMID- 16442035
TI  - Sterile versus nonsterile gloves during Mohs micrographic surgery: infection rate
      is not affected.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) is an outpatient procedure that has
      become the treatment of choice for certain cutaneous malignancies. Although the
      major steps in this procedure are relatively standardized, one difference
      involves the use of sterile or nonsterile, clean gloves during the tumor removal
      phase. OBJECTIVE: This retrospective chart review study was performed to evaluate
      whether infection rates are affected by the use of sterile versus nonsterile
      gloves in the tumor extirpation phase of MMS. METHODS: This study evaluated the
      surgical records of 1,810 consecutive Mohs patients, of which 1,239 Mohs patients
      (1,400 Mohs procedures) met inclusion criteria. Age, sex, tumor diagnosis,
      anatomic location, number of Mohs stages, area of the defect, closure type,
      cartilage exposure, and sterile versus nonsterile glove use were recorded and
      evaluated. RESULTS: Twenty-five infections were identified. Statistically
      significant infection rates were discovered for patients with cartilage
      fenestration with secondary healing and malignant melanoma diagnosis only. There
      was no statistical difference in infection rates with all other measured
      variables to include the use of sterile or clean, nonsterile gloves. CONCLUSION:
      Our study lends support to the contention that clean, nonsterile gloves are safe
      and effective for use in the tumor extirpation phase of MMS, at a significant
      cost savings.

PMID- 16442036
TI  - p75(NGFR) immunostaining for the detection of perineural invasion by cutaneous
      squamous cell carcinoma.
AB  - BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC)
      may portend a poor prognosis for patients. p75NGFR (nerve growth factor receptor)
      is part of a membrane receptor complex that binds nerve growth factor. Its use
      for detecting PNI in CSCC in comparison with S-100 immunohistochemical staining
      has not been explored. OBJECTIVE: To determine whether detection of PNI may be
      improved by staining with p75NGFR compared with hematoxylin and eosin (H&E) and S
      100. METHODS: Thirty-four cases of CSCC were retrospectively evaluated for the
      presence of PNI using standard H&E, as well as S-100 and p75NGFR
      immunohistochemical stains. Staining intensity was correlated to the presence or
      absence of PNI and tumor differentiation. RESULTS: The results showed a positive
      correlation between staining intensity and the presence of PNI detected by
      p75NGFR (p=.04). Using p75NGFR allowed for the detection of seven cases of PNI
      not detected by H&E alone. Five of these cases were detected by S-100, with two
      cases seen by p75NGFR only. Six cases of PNI were detected using S-100 not seen
      on H&E, with one case also not seen using p75NGFR. CONCLUSION: p75NGFR
      immunostaining increased detection of PNI compared with H&E. p75NGFR could serve
      as an alternative to S-100 in the detection of PNI or as part of an
      immunostaining panel for PNI detection.

PMID- 16442037
TI  - Comparative evaluation of the safety and efficacy of botulinum toxin type A and
      topical creams for treating moderate-to-severe glabellar rhytids.
AB  - BACKGROUND: Several nonprescription products purport similar or better outcomes
      than botulinum toxin type A (Botox Cosmetic, Allergan Inc., Irvine, CA, USA) for
      treating wrinkles, but these have not been documented in comparative clinical
      trials. Patients spend millions of dollars annually on the topical products, yet
      there are, to date, no data to support any of the claims made. OBJECTIVE: To
      compare the efficacy and safety of botulinum toxin type A with placebo and three
      topical products in treating moderate-to-severe glabellar lines. METHODS: This
      single-center, randomized, investigator-blinded, parallel study of 77 female
      subjects comprised five treatment groups: botulinum toxin type A, placebo
      injection, StriVectin-SD (Klein-Becker USA, Salt Lake City, UT, USA), DDF Wrinkle
      Relax (Doctor's Dermatologic Formula, HDS Cosmetics, Inc., Yonkers, NY, USA), and
      HydroDerm (Hydroderm, Beverly Hills, CA, USA). Baseline and follow-up visits
      (weeks 4, 8, and 12) assessed safety and key efficacy measures: blinded
      investigator assessment of glabellar line severity on the Facial Wrinkle Scale
      (FWS), subjects' global assessment of overall change in appearance, subject
      ratings of glabellar-related self-perception pre- and post-treatment, and
      satisfaction with treatment. RESULTS: Botulinum toxin type A treatment
      consistently resulted in statistically significant reductions in wrinkle severity
      on the FWS than any comparator (p<.001). Statistically significant improvements
      were similarly observed for subject-reported outcomes and satisfaction with
      botulinum toxin type A treatment, whereas treatment with any of the three topical
      creams did not result in a significant difference from placebo. Three adverse
      events occurred in three subjects who received StriVectin-SD. CONCLUSION:
      Botulinum toxin type A provided significantly greater efficacy and patient
      satisfaction in the treatment of glabellar frown lines than StriVectin-SD,
      Wrinkle Relax, and HydroDerm, and in the objective measurements used, none of the
      topical preparations were better than botulinum toxin.

PMID- 16442038
TI  - Onion extract gel versus petrolatum emollient on new surgical scars: prospective
      double-blinded study.
AB  - BACKGROUND: Cutaneous scars resulting from surgical procedures can be
      erythematous, hypertrophic, pruritic, painful, or cosmetically unacceptable. An
      onion extract-based topical gel (Mederma, Merz Pharmaceuticals, Greensboro, NC,
      USA) has been marketed as a product to improve scar appearance and texture.
      However, few data are available to substantiate these claims. OBJECTIVE: To
      compare the efficacy between the onion extract gel and a petrolatum-based
      emollient (Aquaphor, Beiersdorf, Inc., Wilton, CT, USA) in improving the
      appearance and symptoms of new surgical scars. METHODS: Twenty-four patients with
      new surgical wounds of at least 4 cm in length were enrolled in the study. Using
      a randomized, double-blinded, split-scar study design, each scar was divided into
      two equal portions, and each half was assigned treatment with either onion
      extract gel or petrolatum ointment at the time of suture removal. Each product
      was applied three times daily for 8 weeks, and patients were evaluated at 2, 8,
      and 12 weeks following initiation of treatment. A follow-up telephone interview
      was conducted at least 11 months postoperatively. RESULTS: Scar halves were
      evaluated by blinded investigators for overall cosmetic appearance, erythema, and
      hypertrophy. Patients also independently rated side-specific erythema, pruritus,
      burning, and pain. Using the paired t-test and the Wilcoxon signed rank test, we
      found no statistically significant difference (p < .1) between the two treatment
      groups in any of the outcome variables studied. CONCLUSION: Petrolatum-based
      topical agents constitute standard therapy in the management of postoperative
      wounds. In this side-by-side, randomized, double-blinded, split-scar study, the
      onion extract gel did not improve scar cosmesis or symptomatology when compared
      with a petrolatum-based ointment.

PMID- 16442039
TI  - Graft anchoring in hair transplantation.
AB  - BACKGROUND: Since it is not known precisely how long it will take for grafts to
      be securely anchored after hair transplantation, the advice that the medical
      profession has offered patients regarding postoperative care has been somewhat
      arbitrary. OBJECTIVE: This study attempted to provide scientific data that can be
      useful in refining postoperative hair transplantation protocols. METHODS: Forty
      two patients participated in the study. During their postoperative period, each
      had several grafts pulled to determine at what point they could no longer be
      manually dislodged. RESULTS: For the first 2 days, pulling on a hair always
      resulted in a lost graft. By the sixth day, pulling on a hair no longer dislodged
      the graft. Pulling on an adherent scab always resulted in a lost graft through
      day 5. At 9 days postoperatively, grafts were no longer at risk of being
      dislodged. CONCLUSION: The presence of crusting extends the interval that grafts
      are at risk of being dislodged postoperatively. If one can prevent crust
      formation following hair transplantation, this would both shorten the time
      patients are at risk of losing their grafts and enable them to return to their
      normal hair care routines more quickly.

PMID- 16442040
TI  - Multicenter study of the efficacy and safety of subcutaneous non-animal
      stabilized hyaluronic acid in aesthetic facial contouring: interim report.
AB  - BACKGROUND: Non-animal-stabilized hyaluronic acid (NASHA) gel may offer longer
      lasting cosmetic correction and lower antigenic risk than other soft tissue
      augmentation agents. OBJECTIVE: To assess the efficacy and safety of the NASHA
      gel Restylane SubQ (Q-Med AB, Uppsala, Sweden) in aesthetic facial contouring.
      METHODS: Fifty-seven adult patients seeking cheek and/or chin augmentation
      received subcutaneous and/or supraperiostal injections of Restylane SubQ (20
      mg/mL) at 114 treatment sites; 13 of these patients received "touch-up"
      injections at 20 sites. Efficacy was assessed subjectively using a 5-grade Global
      Aesthetic Improvement Scale at 1, 3, 6, 9, and 12 months after the initial
      treatment. RESULTS: At 3 months post-baseline, patients and investigators
      independently considered the treatment sites to be improved in 96.4% and 100% of
      cases, respectively. Patient- and investigator-assessed response rates
      (proportion of patients showing moderate or better improvement) were 84% and 95%,
      respectively. The majority of reported adverse events were treatment related
      (local injection-site reactions, implantation complications, skin tightness, and
      skin induration), but these were generally of mild intensity and short-lived.
      CONCLUSION: Restylane SubQ is well tolerated and maintains aesthetic correction
      of the cheeks and chin for at least 3 months after subcutaneous and/or
      supraperiostal treatment.

PMID- 16442041
TI  - Improving patient retention after botulinum toxin type A treatment.
AB  - BACKGROUND: Botulinum toxin treatments have been associated with consistently
      high patient satisfaction rates, but calculation of patient retention rates is
      not routinely performed. Retention measurements serve as critical indicators of
      clinical performance and can be optimized by evaluation of current office
      policies and implementation of strategies to improve patient retention. PURPOSE:
      To investigate the reasons patients discontinue botulinum toxin treatments and to
      evaluate the effect of a single intervention intended to improve patient
      retention. METHODS: A retrospective chart review was performed of all patients
      who received botulinum toxin injections in a private cosmetic dermatology
      practice over a 2-year time period to determine the patient retention rate.
      Patients who had discontinued botulinum toxin treatment after a single session
      were surveyed to discern their reasons for terminating treatment. A change in
      office policy was instituted wherein all patients who received their first
      botulinum toxin treatment were required to undergo a 2-week post-treatment
      evaluation to determine treatment effect and to receive touch-up treatment as
      necessary. Retention rates were calculated over the 1-year period immediately
      after initiation of the new policy. RESULTS: The initial patient retention rate
      was 55%. The most common reasons cited for discontinuance of botulinum toxin
      treatments were procedural cost, patient failure to re-schedule, perceived lack
      of product longevity, and clinical effect falling short of expectations. After
      initiation of the mandatory 2-week post-treatment office evaluation, a 67%
      patient retention rate was achieved. CONCLUSIONS: Managing patient expectations
      of botulinum toxin treatments and mandatory post-treatment appointments for
      evaluation of the initial procedure increase the patient retention rate.

PMID- 16442042
TI  - Calculating the pressure and the stiffness in three different categories of class
      II medical elastic compression stockings.
AB  - BACKGROUND: Medical elastic compression stockings (MECSs) are currently
      classified according to the pressure they exert at the ankle at the point of its
      minimum girth (B level). Despite this classification, there are considerable
      differences between MECSs belonging to the same compression class from the same
      manufacturers and between different manufacturers. This makes it difficult for
      the clinician to choose the most suitable MECS for the patient. The stiffness may
      be used to distinguish between MECSs of different brands. OBJECTIVE: To calculate
      the pressure and the stiffness at the B level in three categories of class II
      MECSs from nine different brands. METHODS: Nine different brands of class II
      MECSs that were divided into three categories (flat-knitted custom-made, classic
      round-knitted ready-made, and modern (ultrathin) round-knitted ready-made) were
      tested. The tension of the textile of the MECSs was measured with the Instron
      tester (Instron International Ltd., Edegem, Belgium). The pressures and stiffness
      at the B level were calculated. RESULTS: The pressures exerted by flat-knitted
      custom-made MECSs were higher than those exerted by the ready-made round-knitted
      MECSs. Surprisingly, the former showed higher pressures than those published by
      the European Committee for Standardization. A wide range of stiffness was
      observed within the different brands and within the three different categories of
      MECS. CONCLUSION: Despite their assignment to compression class II, all nine
      brands of MECSs that were tested had widely ranging stiffness. This would
      indicate that the stiffness is an additional important characteristic for
      distinguishing between MECSs from different brands, which should be taken into
      account by the clinician in selecting the most suitable MECSs for the patient.

PMID- 16442043
TI  - Measurement of lower leg compression in vivo: recommendations for the performance
      of measurements of interface pressure and stiffness: consensus statement.
AB  - BACKGROUND: Interface pressure and stiffness characterizing the elastic
      properties of the material are the parameters determining the dosage of
      compression treatment and should therefore be measured in future clinical trials.
      OBJECTIVE: To provide some recommendations regarding the use of suitable methods
      for this indication. METHOD: This article was formulated based on the results of
      an international consensus meeting between a group of medical experts and
      representatives from the industry held in January 2005 in Vienna, Austria.
      RESULTS: Proposals are made concerning methods for measuring the interface
      pressure and for assessing the stiffness of a compression device in an individual
      patient. CONCLUSIONS: In vivo measurement of interface pressure is encouraged
      when clinical and experimental outcomes of compression treatment are to be
      evaluated.

PMID- 16442044
TI  - Photo-epilation results of axillary hair in dark-skinned patients by intense
      pulsed light: comparison between different wavelengths and pulse width.
AB  - BACKGROUND: Recently, intense pulsed light (IPL) sources have been shown to
      provide long-term hair removal. OBJECTIVE: This study examined the photo
      epilatory effects of different wavelengths and pulse width application in the
      same IPL device and compared their efficiencies in Asian skin. METHODS: Twenty
      eight Korean women were treated using hair removal (HR) (600-950 nm filter) and
      27 using HR-D (645-950 nm filter) in the axillary area. Four treatments were
      carried out at intervals of 4 to 6 weeks; follow-ups were conducted 8 months
      after the last treatment. Mean energy settings were 14.9 6 2.0 J/cm2 for HR and
      17.1 6 0.6 J/cm2 for HR-D. Longer pulse widths were applied in case of HR-D
      treatment. Hair counts and photographic evaluation of skin sites were made at
      baseline and at the last follow-up. Final overall evaluations were performed by
      patients and clinicians. RESULTS: Average clearances of 52.8% and 83.4% were
      achieved by HR and HR-D, respectively. No significant adverse effects were
      reported after HR-D treatment. One case each of hypopigmentation and
      hyperpigmentation was reported for HR. CONCLUSION: An IPL source removing 45 nm
      of the emitted spectra and applying a longer pulse width was found to provide a
      safer and more effective means of photo-epilation in Asian patients.

PMID- 16442045
TI  - Laser lipolysis using a novel 1,064 nm Nd:YAG Laser.
AB  - BACKGROUND: We studied the safety and efficacy of a 1,064 nm neodymium:yttrium
      aluminum-garnet (Nd:YAG) laser with a 300-micron fiber for the reduction of small
      unwanted fat areas. METHODS: Thirty subjects with focal areas of fat less than
      100 cc were enrolled. Ten subjects were treated with laser lipolysis and had
      magnetic resonance imaging (MRI) at baseline and 3 months post-treatment. Ten
      subjects had laser lipolysis followed by biweekly treatments with the Tri-active
      system. The last group of 10 subjects served as control. Patients were seen at
      baseline and 1-week, 1-month, and 3-month follow-up visits. RESULTS: Twenty-nine
      patients completed the study. Self-assessment evaluations reported an improvement
      of 37% at the 3-month follow-up visit. MRI demonstrated an average 17% reduction
      in fat volume. Smaller baseline volume areas, such as the submentum, had better
      results, suggesting a dose-response relationship. The most common side effects
      were mild bruising and swelling resolving within 2 weeks. CONCLUSION: Laser
      lipolysis using the 1,064 nm Nd:YAG laser with a 300-micron fiber appears to be a
      very promising procedure that delivers good, reproducible results safely and
      effectively. The advantages include excellent patient tolerance, quick recovery
      time, and the benefit of dermal tightening.

PMID- 16442046
TI  - Treatment of inflammatory facial acne with the 1,450 nm diode laser alone versus
      microdermabrasion plus the 1,450 nm laser: a randomized, split-face trial.
AB  - BACKGROUND: The 1,450 nm laser has been effective in treating acne.
      Microdermabrasion may help treat acne and reduce skin barriers to increase the
      delivery rate of topical anesthetics. OBJECTIVES: To evaluate the efficacy,
      safety, and pain associated with the treatment of inflammatory facial acne with
      the 1,450 nm laser alone versus microdermabrasion plus the 1,450 nm laser.
      METHODS: Twenty patients with facial acne were treated with the 1,450 nm laser
      alone and microdermabrasion plus the 1,450 nm laser in a randomized, split-face
      trial. RESULTS: Laser alone and microdermabrasion plus laser significantly
      reduced the total number of acne lesions. Mean reductions of 53.5% and 55.6% were
      found after three treatments for laser alone and microdermabrasion plus laser,
      respectively. Clinical improvement was maintained 12 weeks after the last
      treatment. Mean pain scores were 5.3 6 1.5 for microdermabrasion plus laser and
      5.2 6 1.5 for laser alone. There was no statistical difference between treatment
      levels for efficacy or pain. There was an average 10% increase in sequential pain
      as the laser treatment progressed. CONCLUSION: The 1,450 nm laser is effective,
      well tolerated, and safe for treating facial acne. This small pilot study did not
      demonstrate increased clinical efficacy or decreased associated pain with the
      addition of microdermabrasion to treatment with the 1,450 nm laser. A larger
      study may be needed to demonstrate any additional benefit.

PMID- 16442047
TI  - Efficacy and safety of the short-pulse erbium:YAG laser in the treatment of
      acquired melanocytic nevi.
AB  - BACKGROUND: Various laser systems have been used in the treatment of acquired
      melanocytic nevi. However, CO2 lasers may cause scarring, and some nevi cannot be
      removed with pigment-specific lasers completely. To date, no study has evaluated
      the efficacy and safety of an erbium:yttrium-aluminum-garnet (YAG) laser, with
      its small penetration depth and fewer adverse effects, in the treatment of
      acquired melanocytic nevi. OBJECTIVE: To investigate the efficacy and safety of
      the short-pulse erbium:YAG laser in the treatment of acquired melanocytic nevi.
      METHODS: The study included 28 nevi in 14 patients. The lesions were pigmented,
      flat, or just palpable nevi. Nevi were irradiated with single-pulse laser energy
      of 1,000 mJ and a pulse duration of 300 microseconds. Fluences between 5.2 and
      14.4 J/cm2 were used. Four months following laser treatment, the entire lesion
      was excised. Each specimen was histopathologically and immunohistochemically
      examined for the presence of nevus cells. RESULTS: Clinically, all of the nevi
      and, histopathologically, 27 of 28 nevi (96%) were completely removed without
      scarring. Post-inflammatory hyperpigmentation was seen in two patients and
      hypopigmentation in three patients. CONCLUSIONS: Short-pulse erbium:YAG laser
      treatment is an effective and safe method for removing acquired melanocytic nevi.

PMID- 16442053
TI  - Defect involving both the cutaneous and the vermilion lip.
AB  - An 89-year-old white male presented for Mohs micrographic surgical extirpation of
      an invasive squamous cell carcinoma on his right lower lip. Extirpation required
      two stages of Mohs surgery and produced a 1.5 x 3.7 cm partial-thickness defect
      involving both the cutaneous and the vermilion lip, with little loss to the
      underlying orbicularis oris muscles (Figure 1). How would you repair the defect?

PMID- 16442048
TI  - Recurrence rates and long-term follow-up after laser resurfacing as a treatment
      for widespread actinic keratoses on the face and scalp.
AB  - BACKGROUND: Diffuse widespread actinic keratoses are difficult to treat, have a
      tendency toward higher recurrence rates, and therefore require ablative
      treatment. Laser resurfacing is one of the treatment modalities that can treat
      whole surface areas. OBJECTIVE: To evaluate patients who underwent laser
      resurfacing for widespread actinic keratoses with long-term follow-up for
      recurrence rates, time until new lesions occur, and the most common side effects.
      METHODS: Retrospective case-control study from 25 patients who underwent laser
      resurfacing for widespread actinic keratoses on the scalp, forehead, or full face
      at our department. Follow-up varied from 7 to 70 months. Recurrence rates,
      adverse effects, and improvement were analyzed through chart analysis. RESULTS:
      The mean average follow-up was 39 months. Forty-four percent of the patient shad
      no recurrence during the time period. Fifty-six percent of the patients developed
      new lesions after treatment but only a few. Of the recurrences, 20% occurred
      within 1 year and 36% occurred after 1 year. The most common short- and long-term
      side effects were infections (12%), hypopigmentation (48%), hyperpigmentation
      (8%), acne (12%), milia (12%), scar formation (8%), and atrophic and/or easily
      bruised skin (20%). CONCLUSION: Laser resurfacing is an effective treatment
      modality for diffuse widespread actinic keratoses with long-term recurrence-free
      intervals.

PMID- 16442054
TI  - A novel technique using a rotation flap for repairing adjacent surgical defects.
AB  - BACKGROUND: The incidence of head and neck carcinomas continues to rise. Surgical
      excision is a frequently used method for removing these carcinomas. It is not
      uncommon to have multiple skin carcinomas present at the same time or in close
      proximity to each other. Therefore, surgeons can be presented with the challenge
      of repairing adjacent surgical defects while avoiding unacceptable wound closure
      tension and distortion of neighboring structures. OBJECTIVE: The presentation of
      a novel method for repairing adjacent surgical defects with a rotation flap.
      MATERIALS: Standard excision tray. CONCLUSION: We present a novel method for
      repairing adjacent surgical defects with a rotation flap. Surgeons are presented
      with adjacent surgical defects and challenged to find the repair option that will
      give the most optimal cosmetic result. The options for closing small adjacent
      surgical defects include making the defects a single large defect for primary
      closure, full-thickness skin grafting, primary closure of each defect separately,
      flap coverage, secondary intention healing, or any combination of these. The use
      of a single rotation flap to cover two adjacent surgical defects provides the
      surgeon with a convenient and cosmetically acceptable option that avoids
      unacceptable wound tension and does not distort neighboring structures.

PMID- 16442055
TI  - Injection necrosis of the glabella: protocol for prevention and treatment after
      use of dermal fillers.
AB  - BACKGROUND: Injection of filler materials into the dermis is well tolerated, with
      few mild and transient side effects. Injection necrosis is a rare but clinically
      important potential complication caused by interruption of the vascular supply to
      the area by compression, injury, and/or obstruction of the vessel(s). The
      glabella is a particular danger zone for injection necrosis regardless of the
      type of filler used. OBJECTIVE: We recommend a protocol that may be used to help
      prevent and treat injection necrosis of the glabella after injection with dermal
      fillers. CONCLUSION: Injection necrosis in the glabellar region may be prevented
      by knowledge of the local anatomy and an understanding of its pathophysiology and
      treated by a suggested protocol.

PMID- 16442056
TI  - Features of regression in dermoscopic diagnosis: a confounding factor? Two
      clinical, dermoscopic-pathologic case studies.
AB  - BACKGROUND: In dermoscopy, the presence of regression areas is generally
      associated with melanocytic lesions and is often considered a clue of malignancy.
      However, some lesions included in the differential diagnosis of melanoma may show
      dermoscopic regression parameters. Regression may indeed be one of the most
      confounding dermoscopic parameters because it tends to cover, or rather to
      destroy, other parameters, thus often hindering a correct diagnosis. OBJECTIVE:
      We propose to raise the issue of the actual diagnostic role of this parameter.
      METHODS: We discuss two clinical cases (melanoma and basal cell carcinoma) with
      major dermoscopic regression features. CONCLUSION: Dermoscopic regression
      parameters should not be regarded as almost pathognomonic signs of melanocytic
      lesions. Rather, they should be taken into account only after having considered
      other dermoscopic parameters of greater diagnostic significance and just as signs
      that may better typify the lesion.

PMID- 16442057
TI  - Office ligation of incompetent perforating veins of the foot.
AB  - BACKGROUND Although exact understanding of the pathophysiology of incompetent
      perforating veins (IPVs) of the foot is lacking and their presence controversial,
      this entity appears to be real and clinically useful. OBJECTIVE To explore this
      clinical phenomenon and improve treatments of varicose vein of the foot. METHODS
      & MATERIALS Nine patients, aged 36-79 years, and a total of ten IPVs of the foot
      underwent office ligation over a period of twenty months. Diagnostic criteria
      included clinical examination, a Doppler Ultrasound (DU) evidence of reflux over
      0.5 seconds, and further confirmation of the reflux and localization by Duplex
      scanning (DS). RESULTS All patients showed improvement in appearance and
      presenting symptoms. Eight patients described the results as good, and one stated
      moderate improvement. One patient required a second surgery to ligate the
      offending perforating vein. No wound related complication occurred, but one
      patient experienced persistent numbness and another had persistent edema of the
      foot. CONCLUSIONS A set of diagnostic criteria including clinical examination,
      Doppler Ultrasound evidence of reflux over 0.5 seconds, and further confirmation
      of the reflux and localization by Duplex scanning appears to be reliable and
      clinically useful.

PMID- 16442058
TI  - Multiple eccrine hidrocystomas: successful treatment with the 595 nm long-pulsed
      dye laser.

PMID- 16442059
TI  - Fractional photothermolysis for treatment of poikiloderma of civatte.
AB  - Poikiloderma of Civatte refers to a change in the skin where there is atrophy,
      hyper- and hypopigmentation, and dilation of fine blood vessels (telangiectasia).
      These alterations often cause cosmetic disfigurement, most commonly in middle
      aged or elderly women with a fair complexion. Several treatment modalities, based
      on the theory of selective photothermolysis, including argon lasers, KTP lasers,
      pulsed dye lasers, and intense pulsed light devices, have been used to treat this
      condition in the past. Clinical experience has shown that complete clearing is
      difficult to achieve. Moreover, depending on the modality used, adverse effects,
      such as scarring with irregular hypopigmentation, post-inflammatory
      hyperpigmentation, post-treatment purpura, mottled appearance, crusting, and
      erythema, have been reported. Multiple sessions with these treatments are usually
      necessary to obtain optimal clearing.

PMID- 16442060
TI  - Epidermodysplasia verruciformis: an unusual presentation.
AB  - BACKGROUND Epidermodysplasia verruciformis (EV) is a rare autosomal recessive
      genetic disorder of the immune system manifested by increased susceptibility to
      cutaneous human papillomavirus (HPV) infection beginning from the early years of
      life, and compromising lesions resembling flat warts, especially on the distal
      extremities and the face; but malignant transformation occurs in sun-exposed
      areas within the third or fourth decade of life. OBJECTIVE We describe two case
      reports of epidermodysplasia verruciformis, one of which was onset and had more
      aggressive features than the usual presentation. METHODS Intermittent surgical
      excision of the tumoral lesions were performed in the first case, whereas only
      one surgical intervestion was sufficient in the second case. RESULTS The early
      onset case was more aggressive, and new tumoral lesions were seen, whereas the
      other patients was free of the disease for 2 years.CONCLUSION Epidermodysplasia
      verruciformis possess multi factorial etiologies, and the main prognostic factor
      of the behavior of the disease may be the family history and genetic
      susceptibility.

PMID- 16442061
TI  - Aggressive basal cell carcinoma with invasion of the parotid gland, facial nerve,
      and temporal bone.
AB  - Aggressive variants of basal cell carcinoma (BCC), such as infiltrating,
      morpheaform, and basosquamous types, are associated with invasion of underlying
      tissues and are often difficult to treat.1 BCCs located in embryonic fusion
      planes, such as the periauricular region, are thought to exhibit deep extension
      and, subsequently, high recurrence rates, although this theory has been
      challenged and remains controversial.2-4 Despite the known features of aggressive
      BCC, parotid gland invasion and temporal bone and facial nerve involvement are
      rarely reported occurrences. We describe two patients with morpheaform BCC in the
      periauricular region demonstrating direct invasion of the parotid gland and
      concomitant facial nerve involvement. These patients require complex surgical
      management, as highlighted in this report.

PMID- 16442062
TI  - Lymphoepithelioma-like carcinoma of the skin: a report of two cases treated with
      complete microscopic margin control and review of the literature.
AB  - Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare cutaneous neoplasm
      with microscopic similarities to non-cutaneous lymphoepitheliomatous
      malignancies, particularly undifferentiated carcinoma of the nasopharynx. It can
      be clinically and histologically confused with other benign and malignant tumors.
      If not adequately treated, recurrence and distant metastasis are probable. We
      present two cases of LELCS treated surgically with complete microscopic margin
      control (one by the Mohs method and the other with en face permanent sections)
      and review the literature.

PMID- 16442063
TI  - Periungual basal cell carcinoma: case report and literature review.
AB  - BACKGROUND Basal cell carcinoma, the most common malignancy in humans, rarely
      occurs on the nail unit and may be frequently misdiagnosed clinically. OBJECTIVES
      To present a case of basal cell carcinoma of the nail unit successfully treated
      with the mohs technique and to review the literature regarding this unique
      presentation of this tumor. MATERIALS AND METHODS: Case report and review of the
      English literature of nail unit basal cell carcinoma. RESULTS In addition to the
      currently described patient, 17 other patients with nail unit basal cell
      carcinoma have been reported. The tumor occurred approximately 3 times more often
      on the fingers then on the toes and had a slight predilection to occur in men.
      Ulceration, noted in more than one-half of patients, was the most common
      presentation of nail unit basal cell carcinoma. Mohs micrographic surgery. Often
      with second intention healing, was successfully employed in 39% of patients.
      CONCLUSIONS Basal cell carcinoma infrequently involves the nail unit and often
      presents as ulceration. Adequate biopsy of the lesion is essential in making a
      timely diagnosis. Mohs micrographic surgery with second intension healing is an
      effective treatment that may offer excellent cosmetic and functional results.

PMID- 16442064
TI  - Radical excision and mesh-skin grafting for giant anorectal condyloma acuminatum.
AB  - BACKGROUND Giant Condyloma Acuminatum (GCA) presents difficulties in therapeutic
      management, mainly due to local invasion and recurrences. Treatment measures vary
      from topical agents to aggressive methods such as surgical excision, radiation,
      laser surgery, chemotherapy, immunotherapy or their combination. METHOD A 48-year
      old heterosexual, HIV-negative male with a 20 year-year history of GCA, following
      an unsuccessful surgical operation, underwent radical excision with immediate
      mesh-skin grafting. CONCLUSION The absence of relapse and the excellent cosmetic
      results obtained one and a half years post-operative may put this treatment
      option in the first line of treatment choices for GCA

PMID- 16442065
TI  - Carbon dioxide laser de-epithelialization: selective removal of the epidermis
      with minimal change to the basement membrane zone.

PMID- 16442066
TI  - Dressing and covering of the recipient area after suction-blistered epidermal
      grafting: is it necessary?

PMID- 16442067
TI  - Re: Campbell RM et al, post-Mohs micrographic surgical margin tissue evaluation
      with permanent histopathologic sections.

PMID- 16442068
TI  - Safety climate and self-reported injury: assessing the mediating role of employee
      safety control.
AB  - To further reduce injuries in the workplace, companies have begun focusing on
      organizational factors which may contribute to workplace safety. Safety climate
      is an organizational factor commonly cited as a predictor of injury occurrence.
      Characterized by the shared perceptions of employees, safety climate can be
      viewed as a snapshot of the prevailing state of safety in the organization at a
      discrete point in time. However, few studies have elaborated plausible mechanisms
      through which safety climate likely influences injury occurrence. A mediating
      model is proposed to link safety climate (i.e., management commitment to safety,
      return-to-work policies, post-injury administration, and safety training) with
      self-reported injury through employees' perceived control on safety. Factorial
      evidence substantiated that management commitment to safety, return-to-work
      policies, post-injury administration, and safety training are important
      dimensions of safety climate. In addition, the data support that safety climate
      is a critical factor predicting the history of a self-reported occupational
      injury, and that employee safety control mediates the relationship between safety
      climate and occupational injury. These findings highlight the importance of
      incorporating organizational factors and workers' characteristics in efforts to
      improve organizational safety performance.

PMID- 16442069
TI  - Leishmania infantum released proteins specifically regulate cytokine expression
      and production patterns by CD4+ and CD8+ T cells.
AB  - Specific immune responses by CD4+ and CD8+ T cells, from two infected mice
      strains (BALB/c and C57BL/6), induced by High, Inter and Low protein fractions
      released by Leishmania infantum, were assessed through the evaluation of IL-12,
      IFN-gamma and IL-10 mRNA by real-time PCR and respective protein production by
      ELISA. During infection establishment, High and Inter fractions directed both
      mice strains T cells subsets to increase the production of IFN-gamma, associated
      to IL-12 release. Later on, parasite replication augmented in BALB/c and
      stabilised in C57BL/6 mice. Inter fraction induced CD4+ T cells to maintain IFN
      gamma production, with the simultaneous release of IL-12 by both cell subsets in
      BALB/c mice and by CD8+ T cells in C57BL/6 mice. These observations suggested a
      prophylactic potential for Inter fraction which was able to induce Th1 response
      with IL-12 involvement, required for the maintenance of memory cells, in mice
      strains with different parasitic evolution.

PMID- 16442070
TI  - [Sigmoid colon cancer: laparoscopic or conventional resection?].

PMID- 16442071
TI  - [The use of head CT scan in adult trauma victims: an algorithm].
AB  - INTRODUCTION: The purpose of this study was to identify, through recursive
      partitioning, clinically relevant criteria which predict the need for acute
      neurosurgical intervention in a group of patients with mild head injury.
      MATERIALS AND METHODS: A retrospective cohort of all adult patients, from April
      2000 to March 2001, who sustained a blunt trauma and underwent head CT scan, was
      reviewed. The following inclusion criteria for mild head injury were used:
      initial Glasgow Coma Scale (GCS) ranging from 13 to 15; no loss of consciousness
      lasting more than one hour; no obvious skull fracture; a cranial CT scan
      performed. We collected demographic and trauma related data, interventions and
      outcome. Univariate and multivariate analyses were undertaken. In parallel,
      recursive partitioning was carried out using all variables to elaborate a
      decision algorithm. RESULTS: There were 405 patients in the sample. CT identified
      lesions in 12% of patients. Twelve patients (3%) required acute neurosurgical
      intervention. The recursive partitioning analysis identified three significant
      sequential nodes: deterioration of the GCS; an initial GCS of 13 vs 14 or 15; and
      the presence of associated injuries or comorbid conditions. CONCLUSIONS: A simple
      three step rule predicts the need for acute neurosurgical intervention based on
      clinical findings: a deteriorating GCS; an initial GCS of 13; and the presence of
      associated injuries or comorbid conditions.

PMID- 16442072
TI  - Maximal dynamic grip force and wrist torque: the effects of gender, exertion
      direction, angular velocity, and wrist angle.
AB  - The objective of this study was to examine the effects of gender, exertion
      direction, angular velocity and wrist angle on simultaneous grip force and wrist
      torque under the isokinetic condition. The study used 20 participants (10 males
      and 10 females) and included 6 angular velocities (15, 30, 45, 60, 75, and 90
      degrees /s) and 2 wrist exertion directions (flexion and extension) over the
      wrist range of motion of 70 degrees flexion to 60 degrees extension in 5 degrees
      increments. Similar to other studies, males and flexion exertion produced larger
      forces than females and extension exertion, respectively. However, the largest
      forces were generated at near extreme flexion of the wrist and the dependent
      variable of angular velocity was not practically significant. These results can
      contribute to the evaluation of cumulative trauma syndromes, but there is a need
      for more research on the dynamic measures of the hand and wrist complex and for
      standard development for dynamic force measurement.

PMID- 16442073
TI  - Calcineurin dephosphorylates the C-terminal region of filamin in an important
      regulatory site: a possible mechanism for filamin mobilization and cell
      signaling.
AB  - Filamin is a phosphoprotein that organizes actin filaments into networks. We
      report that a purified C-terminal recombinant region of filamin is a suitable
      substrate for calcineurin in vitro. Furthermore, 1 microM cyclosporin A (CsA), a
      specific calcineurin inhibitor, reduced the dephosphorylation of the recombinant
      fragment in 293FT cells. Mutagenesis analysis showed that a dephosphorylation
      step occurred in Ser 2152, which was previously shown to provide resistance to
      calpain cleavage when endogenous PKA is activated. In contrast, phosphorylation
      of Ser 2152 was recently reported to be necessary for membrane dynamic changes.
      In this regard, we found that CsA protects filamin in platelets from calpain
      degradation. Results could be combined with available information in a single
      model, assuming that some of the peptide fragments released by calcineurin
      regulated calpain action could mediate actions in downstream pathways, which may
      help to resolve the controversies reported on the role of filamin phosphorylation
      in actin dynamics.

PMID- 16442074
TI  - The importance of valency in enhancing the import and cell routing potential of
      protein transduction domain-containing molecules.
AB  - Protein transduction domains (PTDs) are peptides that afford the internalization
      of cargo macromolecules (including plasmid DNA, proteins, liposomes, and
      nanoparticles). In the case of polycationic peptides, the efficiency of PTDs to
      promote cellular uptake is directly related to their molecular mass or their
      polyvalent presentation. Similarly, the efficiency of routing to the nucleus
      increases with the number of nuclear localization signals (NLS) associated with a
      cargo. The quantitative enhancement, however, depends on the identity of the PTD
      sequence as well as the targeted cell type. Thus the choice and multivalent
      presentation of PTD and NLS sequences are important criteria guiding the design
      of macromolecules intended for specific intracellular localization. This review
      outlines synthetic and recombinant strategies whereby PTDs and signal sequences
      can be assembled into multivalent peptide dendrimers and promote the uptake and
      routing of their cargoes. In particular, the tetramerization domain of the tumour
      suppressor p53 (p53tet) is emerging as a useful scaffold to present multiple
      routing and targeting moieties. Short cationic peptides fused to the 31-residue
      long p53tet sequence resulted in tetramers displaying a significant enhancement
      (up to 1000 fold) in terms of their ability to be imported into cells and
      delivered to the cell nucleus in relation to their monomeric analogues. The
      design of future polycationic peptide dendrimers as effective delivering vehicles
      will need to incorporate selective cell targeting functions and provide solutions
      to the issue of endosomal entrapment.

PMID- 16442075
TI  - Glycosylation in the Fc domain of IgG increases resistance to proteolytic
      cleavage by papain.
AB  - IgG antibodies (Abs) and fragments of IgG Abs are becoming major biotherapeutics
      to treat an assortment of human diseases. Commonly prepared fragments of IgGs
      include Fc, Fab, and F(ab')2 fragments, all of which can be made using the
      sulfhydryl protease papain, although prolonged digestion times and/or excessive
      amounts of papain typically result in further cleavage of the Fc domain into
      smaller fragments. During our attempts to use papain to isolate Fc fragments from
      different IgG monoclonal Abs, it was observed that prior removal of Fc glycans
      resulted in a faster rate of papain-mediated degradation of the Fc domain.
      Subsequent time-course experiments comparing glycosylated and deglycosylated
      versions of IgG antibodies showed that the majority of molecules in a
      deglycosylated IgG sample were converted into Fab, Fc, and smaller Fc fragments
      in less than one hour, whereas the original glycosylated IgG required more than
      two hours to convert into a comparable amount of Fab and Fc fragments.
      Furthermore, whereas papain digestion converted almost all of a deglycosylated Fc
      fragment into smaller fragments of approximately 10 and approximately 12 kDa
      within 4 h, more than 40% of a glycosylated Fc fragment remained intact even
      after 24 h of digestion. These results indicate that the presence of CH(2) domain
      glycans in either IgGs or purified Fc fragments increases resistance to papain
      digestion. Increased sensitivity of non-glycosylated Fc domains to papain is
      consistent with the Fc domains lacking a defined structure, as exemplified by
      their inability to bind Fcgamma receptors, since misfolded proteins are often
      degraded by proteases because of increased accessibility of their proteolytic
      cleavage sites. Based on these observations it is possible to use papain
      sensitivity as a means of assessing proper Fc structure of IgG molecules.

PMID- 16442076
TI  - Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia.
AB  - In this work, we demonstrate that endothelial nitric oxide synthase is capable of
      anoxic reduction of nitrite anions to nitric oxide at physiological pH by
      absorption and EPR spectroscopy and electrochemical measurements. The nitrite
      reduction is achieved at the oxygenase domain of the protein and proceeds even in
      the absence of the tetrahydrobiopterin cofactor. The nitrite pathway increases by
      sixfold the NO production with respect to the regular arginine pathway under
      hypoxia, which is largely blocked. Therefore, basal levels of NO release could be
      sustained by anoxic nitrite reduction. The reaction suggests a new pathway for
      fast NO delivery under hypoxia, precisely when the vasodilating properties of
      nitric oxide are most needed.

PMID- 16442077
TI  - Structure and functional regulation of the CD38 promoter.
AB  - CD38 has multiple roles in biology, including T lymphocyte signaling, neutrophil
      migration, neurotransmission, cell proliferation, apoptosis, and bone remodeling.
      To study the transcriptional control of the CD38 gene, we cloned a putative 1.8
      kb promoter fragment from a rabbit genomic DNA library. Primer extension analysis
      indicated two transcription start sites consistent with the absence of a TATA
      box. Sequence analysis revealed several AP-1, AP-4, myo-D, GATA, and SP-1
      sequences. MC3T3.E1 (osteoblast) or RAW-C3 (osteoclast precursor macrophage)
      cells were then transfected with the CD38 promoter or its deletion fragments
      ligated to the luciferase reporter gene. Except for the shortest 41 bp fragment,
      all fragments showed significant luciferase activity. There was a marked
      stimulation of basal activity in the 93 bp fragment that contained a GC box and
      SP-1 site. Furthermore, there were significant differences in the activity of the
      fragments in MC3T3.E1 and RAW-C3 cells. Intracellular Ca(2+) elevations by
      ionomycin (10muM) in MC3T3.E1 cells inhibited promoter activity, except in the
      short 41 bp. In contrast, cAMP elevation by exposure to forskolin (100 microM)
      inhibited activation of all fragments, except the 0.6 and 1.2kb fragments.
      Finally, TNF-alpha stimulated promoter activity in RAW-C3 cells transfected with
      the 93 bp and 1.0 kb fragments, consistent with the stimulation of CD38 mRNA by
      TNF-alpha. Physiologically, therefore, modulation of the expression of the NAD(+)
      sensing enzyme, CD38, by Ca(2+), cAMP, and cytokines, such as TNF-alpha may
      contribute to coupling the intense metabolic activity of osteoclasts and
      osteoblasts to their respective bone-resorbing and bone-forming functions.

PMID- 16442078
TI  - Determination of genomic breakpoints in an epileptic patient using genotyping
      array.
AB  - Recent advances in DNA microarray technology have enabled the identification of
      small alterations throughout the genome. We used standard karyotype analysis,
      followed by DNA microarray analysis and PCR to precisely map the chromosomal 4p
      deletion and determine the deletion breakpoints in the genome of an epileptic
      patient. The karyotype of the patient was 46,XY,del(4)(p15.2p15.3) as determined
      by G-banding analysis. We used a high-density oligonucleotide genotyping array to
      estimate the size of the deletion (4.5 Mb) and to locate the breakpoints within a
      9-kb region on one side of the deletion and a 100-kb region on the other side. We
      amplified by PCR and sequenced the genomic region encompassing the breakpoints,
      and mapped the deletion to regions extending from 21648457 to 26164287 and from
      26164505 to 26167493, respectively (chromosome 4 of NCBI Homo sapiens Genome
      Build 35.1). The deletion involves 18 genes, one of which (CCKAR) is partially
      deleted.

PMID- 16442079
TI  - High-throughput assay of DNA methylation based on methylation-specific primer and
      SAGE.
AB  - Mapping of genomic DNA methylation is a dispensable part of functional genome. We
      have developed a novel method based on methylation-specific primer and serial
      analysis of gene expression, called MSP-SAGE, with potential of high-throughput
      quantification of genomic DNA methylation. We used a 6-mer methylation-specific
      primer to extend the methylated CpG sequences other than non-methylated CpG
      sequences. The 17 bp tags contained methylated CpG sequence, which were obtained
      from extended methylation sequence by digestion of restriction endonuclease, and
      then the tags were concatenated and cloned for sequencing. We can identify the
      locations of methylation according to the sequences of tags and quantify the
      methylation status from the frequency of the tags. MSP-SAGE has a good linearity
      in a broad methylation range from 5% to 100% with good accuracy and high
      precision. The proof-of-principle study shows that MSP-SAGE is a reliable high
      throughput assay for quantification of DNA methylation.

PMID- 16442080
TI  - A role for AMPA receptors in mood disorders.
AB  - Major antidepressant agents increase synaptic levels of monoamines. Although the
      monoamine hypothesis of depression remains a cornerstone of our understanding of
      the pathophysiology of depression, emerging data has suggested that the alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtype of
      glutamate receptor may also play a pivotal role in depression. Positive
      allosteric modulators of AMPA receptors increase brain levels of brain-derived
      neurotrophic factor (BDNF) that impacts the viability and generation of neurons
      in key brain structures. AMPA receptor potentiators are active in rodent models
      predictive of antidepressant efficacy. The mechanisms by which AMPA receptor
      potentiators produce these biological effects, however, are uncertain. Current
      evidence points to an antidepressant mechanism that is independent of
      monoaminergic facilitation that is driven by neurogenesis, a process facilitated
      by increased BDNF expression. However, alternative hypotheses need to be
      considered given uncertainties in the relationship between BDNF increases and the
      effects of conventional antidepressant medications. Electrophysiological and
      protein conformational data indicate that structural variants of AMPA receptor
      potentiators can differentially modulate AMPA receptor-mediated currents,
      although the manner in which this impacts antidepressant efficacy is yet to be
      understood. Conventional antidepressants such as fluoxetine positively modulate
      AMPA receptors. This potentiation is engendered by specific phosphorylation
      pathways activated through the dopamine- and cAMP-regulated phosphoprotein of Mr
      32,000 (DARPP-32). Other novel compounds with antidepressant-like effects in
      rodents may also produce their in vivo effects through potentiation of AMPA
      receptors. Thus, AMPA receptor potentiation might be a general mechanism through
      which the clinical outcome of antidepressant efficacy is achieved.

PMID- 16442081
TI  - Imaging genetics: perspectives from studies of genetically driven variation in
      serotonin function and corticolimbic affective processing.
AB  - Advances in molecular biology and neuroimaging have provided a unique opportunity
      to explore the relationships between genes, brain, and behavior. In this review,
      we will briefly outline the rationale for studying genetic effects on brain
      function with neuroimaging. We will then use studies of genetically driven
      variation in serotonin transporter function on corticolimbic structure and
      function to highlight the effectiveness of this strategy to delineate biological
      pathways and mechanisms by which individual differences in brain function emerge
      and potentially bias behavior and risk for psychiatric illness. In a series of
      studies, a relatively frequent regulatory variant of the human serotonin
      transporter gene (5-HTTLPR) has been demonstrated to bias the reactivity of the
      amygdala to salient environmental cues. Moreover, the 5-HTTLPR affects the
      development of a broader corticolimbic circuit and alters the functional
      integration of emotional information between the amygdala and medial prefrontal
      cortex. In turn, corticolimbic circuit function predicts individual differences
      in an experimental index of temperamental anxiety and, thus, might reflect a
      predictive biological marker of increased risk for mood disorders associated with
      the 5-HTTLPR.

PMID- 16442082
TI  - BDNF Val66Met allele is associated with reduced hippocampal volume in healthy
      subjects.
AB  - BACKGROUND: A frequent polymorphism of the brain-derived neurotrophic factor
      (BDNF) gene (val(66)met) has been suggested to modulate hippocampal neuronal
      plasticity and has been associated with individual variations in emotional
      reactivity traits and episodic memory. METHODS: The hippocampal formation was
      outlined in high-resolution anatomical magnetic resonance imaging (MRI) data in a
      sample of 36 healthy volunteers and compared between individuals as a function of
      the presence of the met-BDNF allele. Both whole-brain volume corrected and
      uncorrected data were tested for effects of genotype, sex, and age. RESULTS: The
      met-BDNF allele was associated with an 11% reduction in the volume of the
      hippocampal formation. CONCLUSIONS: In spite of a relatively small sample size,
      the presence of the met-BDNF allele was found associated with a reduced volume of
      the hippocampal formation in healthy volunteers and may represent a vulnerability
      factor for the development of disease processes associated with the dysfunction
      of this brain region.

PMID- 16442083
TI  - Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology.
AB  - Neuregulin 1 (NRG1) is a leading schizophrenia susceptibility gene. The NRG1
      locus on chromosome 8p shows linkage to the disorder, and genetic association has
      been found between schizophrenia and various non-coding polymorphisms and
      haplotypes, especially at the 5' end of the NRG1 gene, in many but not all case
      control and family studies. NRG1 is a pleiotropic growth factor, important in
      nervous system development and functioning; roles include the modulation of
      neuronal migration, synaptogenesis, gliogenesis, neuron-glia communication,
      myelination, and neurotransmission. Understanding the neurobiology of NRG1 and
      its involvement in schizophrenia is challenged by the complexity of the gene,
      which gives rise to multiple functionally distinct isoforms, including six
      "types" of NRG1 defined by 5' exon usage. Type IV and type I NRG1 may be
      particularly relevant to schizophrenia, with initial data showing altered
      expression of these isoforms in the disorder or in association with NRG1 risk
      alleles. We review the structure and functions of NRG1, consider the evidence for
      and against it being a schizophrenia susceptibility gene, and discuss mechanisms
      that might underlie the contribution of NRG1 to disease pathophysiology.

PMID- 16442085
TI  - Semantic activation, letter search and N400: A reply to Mari-Beffa, Valdes,
      Cullen, Catena and Houghton (2005).
AB  - From a behavioural point of view, the automaticity of semantic activation was
      denied because letter search eliminates semantic priming effects on RT. From a
      neuroscience point of view, two recent studies used the N400 to test this claim
      with antithetic results. Here, we replicate N400 priming effects in the letter
      search task. The negative results might be traced back to the use of an
      inappropriate reference electrode. Thus, the theory of semantic activation being
      an automatic process should not be abandoned prematurely.

PMID- 16442084
TI  - Lesions of the habenula produce stress- and dopamine-dependent alterations in
      prepulse inhibition and locomotion.
AB  - The habenula complex modulates the activity of dopamine and serotonin systems in
      the brain. An important question remains whether there is a link between habenula
      dysfunction and monoamine-related disorders, such as schizophrenia. In this
      study, we describe an interaction between habenula lesions and stress that
      produces long-lasting effects on behavior. Mice received control lesions or
      bilateral electrolytic lesions of the habenula and were tested for fear
      potentiated startle and freezing measures of conditioned fear. They were also
      tested for prepulse inhibition (PPI) and locomotor activity in the presence or
      absence of a dopaminergic agonist (apomorphine) or an atypical antipsychotic with
      mixed dopamine/serotonin antagonist properties (clozapine). There were no
      detectable effects of habenula lesions on fear conditioning and no effects on PPI
      in the absence of stress. However, following conditioned fear stress, habenula
      lesioned animals showed decreased PPI which normalized with clozapine. Lesioned
      animals also showed diminished activity at baseline, with hyperlocomotion
      following apomorphine. These data support the hypothesis that the habenula may be
      normally involved in stress-dependent regulation of monoamine systems.

PMID- 16442086
TI  - Phosphorylation of Extracellular Signal-Regulated Kinase in medullary and upper
      cervical cord neurons following noxious tooth pulp stimulation.
AB  - The phosphorylated Extracellular Signal-regulated Kinase (pERK) and Fos
      expression and masticatory muscle activity were analyzed in rats with capsaicin
      induced acute inflammation of the tooth pulp in order to clarify the role of the
      spinal trigeminal nucleus and upper cervical spinal cord in tooth pulp pain.
      Digastric and masseteric muscle activities were significantly increased following
      capsaicin injection into the molar tooth pulp but not after vehicle treatment.
      The pERK-like immunoreactive (LI) neurons were observed in the subnuclei
      interpolaris-caudalis transition (Vi/Vc) zone, the paratrigeminal nucleus (Pa5)
      and the superficial laminae of the caudal Vc/C2 zone. The pERK expression was
      detected as early as 2 min and peaked at 5 min after capsaicin or vehicle
      injection. The pERK expression in the Vi/Vc zone and Pa5 was bilateral, whereas
      it was predominantly ipsilateral in the caudal Vc/C2 zone. The capsaicin
      treatment of the whisker pad produced pERK expression in the rostro-caudal middle
      portion of the ipsilateral Vc, but small number of pERK-LI cells were observed
      after vehicle treatment. The pERK expression was similar in the Vi/Vc zone
      following capsaicin injection into the upper or lower molar tooth pulp, whereas
      the pERK expression was in the lateral portion of the caudal Vc/C2 zone after
      upper molar injection and restricted to the medial portion of the Vc/C2 zone
      after the lower molar capsaicin. These data were confirmed with Western blots.
      There were differences in the distribution of Fos protein-like immunoreactive
      (LI) cells and pERK-LI cells following tooth pulp stimulation. After capsaicin
      application into the upper molar tooth pulp, no pERK-LI cells were observed in
      the ventral part of the Vi/Vc zone, whereas many Fos protein-LI cells were
      expressed in this region. The difference in the distribution pattern of pERK- and
      Fos protein-LI cells in the Vi/Vc zone suggests their differential temporal
      expression profiles after capsaicin. The present findings suggest that tooth-pulp
      driven neurons in the spinal trigeminal nucleus are involved in tooth pulp pain
      through activation of the intracellular signal transduction pathway that involves
      earlier ERK phosphorylation and subsequent Fos expression.

PMID- 16442087
TI  - Boron ameliorates fulminant hepatic failure by counteracting the changes
      associated with the oxidative stress.
AB  - Boron has well-defined biological effects and may be of therapeutic benefit. In
      the current paper, the effect of boron in the form of borax was tested in
      experimental animal model of fulminant hepatic failure (FHF). The syndrome was
      induced in female Wistar rats by three consecutive daily intraperitoneal
      injections of thioacetamide (400 mg/kg). In the treatment groups, rats received
      borax (4.0 mg/kg) orally for three consecutive days followed by thioacetamide.
      The group administered with thioacetamide plus vehicle, and the borax alone
      treated rats served as controls. In all groups, rats were terminated 4 h after
      administering the last dose of thioacetamide, and the tissue/serum was used to
      measure hepatic levels of thiobarbituric acid reactive substances, reduced
      glutathione, and various enzymes associated with oxidative stress including
      peroxide metabolizing enzymes and xanthine oxidase. In thioacetamide treated
      group, many fold increase in the activity level of serum marker enzymes
      suggesting FHF was observed that could be brought down significantly in rats
      receiving boron. Modulation and a correlation in the activity level of oxidant
      generating enzyme and lipid peroxidation as well as hepatic glutathione level was
      also observed in rats receiving thioacetamide. In the group receiving boron
      followed by thioacetamide, these changes could be minimized moderately. The
      activity level of the peroxide metabolizing enzymes and the tripeptide
      glutathione, which decreased following thioacetamide treatment were moderately
      elevated in the group receiving boron followed by thioacetamide. The data clearly
      shows that borax partly normalizes the liver and offsets the deleterious effects
      observed in FHF by modulating the oxidative stress parameters.

PMID- 16442088
TI  - Is motion extrapolation employed in multiple object tracking? Tracking as a low
      level, non-predictive function.
AB  - In a series of five experiments, we investigated whether visual tracking
      mechanisms utilize prediction when recovering multiple reappearing objects. When
      all objects abruptly disappeared and reappeared mid-trajectory, it was found that
      (a) subjects tracked better when objects reappeared at their loci of
      disappearance than when they reappeared in their extrapolated trajectories, (b)
      disappearance episodes ranging from 150 to 900 ms had virtually no differential
      effect on performance, (c) tracking deteriorated monotonically as a function of
      displacement magnitude during disappearance, and (d) tracking did not depend on
      whether objects moved in predictable paths. Even objects that reappeared backward
      in their trajectories were tracked dramatically better than objects that
      reappeared in their extrapolated trajectories. When all objects disappeared and
      reappeared in ways that implicated the presence of an occluder (i.e., with
      occlusion and disocclusion cues along fixed contours), tracking again was not
      predictive, and performance deteriorated with increased displacement. When
      objects reappeared predictably in 75% of trials, they were still tracked better
      when they reappeared at their points of disappearance. Theoretical implications
      of a non-predictive multiple object tracking mechanism are discussed.

PMID- 16442089
TI  - Cryopreservation does not alter the allogenicity and development of vasculopathy
      in post-transplant rat aortas.
AB  - BACKGROUND: Cryopreservation is a valuable technique for storing heart valve and
      vascular allografts. However, the biological ramifications of cryopreservation
      are still unclear; therefore, using animal experiments we assessed how
      'cryopreservation' influences graft allogenicity and cell viability. METHODS:
      Thoracic aortas of Lewis rats were prepared as fresh (F) or cryopreserved (CP)
      grafts, and implanted into the infrarenal aorta of Lewis or Brown Norway rats
      (BNs). The grafts and spleens were harvested at post-operative day 7 and 28
      (POD7, POD28) for analyses. RESULTS: First, the systemic immune response to
      transplantation was estimated by mixed lymphocyte reaction analyses using spleen
      cells from naive or recipient BNs. The alloreactivity of the recipients increased
      to 1.5 times that of the naive BNs at POD7 and POD28, when stimulated by
      mitomycin C-treated Lewis spleen cells. Second, local immune response was
      estimated by TNFalpha, IFNgamma, and iNOS mRNA expression in the grafts by
      quantitative PCR, which revealed 20- to 40-fold increases at POD28 after
      allotransplantation. Third, endothelial cell viability was estimated by
      endothelial NOS mRNA expression level: it was similar and highest in F and CP
      grafts before transplantation then significantly decreased after both syngeneic
      and allogeneic transplantation. Finally, intimal hyperplasia, expressed by I/M
      ratio, developed over time after allotransplantation, reaching 2.5 times the
      thickness of F grafts before transplantation. The results of these experiments
      revealed no difference between F and CP grafts before and after transplantation.
      CONCLUSION: Cryopreservation did not modify the allogenicity of vascular
      allografts and had minimal adverse impacts on graft cell viability.

PMID- 16442090
TI  - Nervous system development of the sea cucumber Stichopus japonicus.
AB  - The nervous system development of the sea cucumber Stichopus japonicus was
      investigated to explore the development of the bilateral larval nervous system
      into the pentaradial adult form typical of echinoderms. The first nerve cells
      were detected in the apical region of epidermis in the late gastrula. In the
      auricularia larvae, nerve tracts were seen along the ciliary band. There was a
      pair of bilateral apical ganglia consisted of serotonergic nerve cells lined
      along the ciliary bands. During the transition to the doliolaria larvae, the
      nerve tracts rearranged together with the ciliary bands, but they were not
      segmented and remained continuous. The doliolaria larvae possessed nerves along
      the ciliary rings but strongly retained the features of auricularia larvae nerve
      pattern. The adult nervous system began to develop inside the doliolaria larvae
      before the larval nervous system disappears. None of the larval nervous system
      was observed to be incorporated into the adult nervous system with
      immunohistochemistry. Since S. japonicus are known to possess an ancestral mode
      of development for echinoderms, these results suggest that the larval nervous
      system and the adult nervous system were probably formed independently in the
      last common ancestor of echinoderms.

PMID- 16442091
TI  - Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme.
AB  - To determine the importance of fibroblast growth factor receptors (fgfrs) 1 and 2
      in the metanephric mesenchyme, we generated conditional knockout mice (fgfr(Mes-/
      )). Fgfr1(Mes-/-) and fgfr2(Mes-/-) mice develop normal-appearing kidneys.
      Deletion of both receptors (fgfr1/2(Mes-/-)) results in renal aplasia.
      Fgfr1/2(Mes-/-) mice develop a ureteric bud (and occasionally an ectopic bud)
      that does not elongate or branch, and the mice do not develop an obvious
      metanephric mesenchyme. By in situ hybridization, regions of mutant mesenchyme
      near the ureteric bud(s) express Eya1 and Six1, but not Six2, Sall1, or Pax2,
      while the ureteric bud expresses Ret and Pax2 normally. Abnormally high rates of
      apoptosis and relatively low rates of proliferation are present in mutant
      mesenchyme dorsal to the mutant ureteric bud at embryonic day (E) 10.5, while
      mutant ureteric bud tissues undergo high rates of apoptosis by E11.5. Thus, fgfr1
      and fgfr2 together are critical for normal formation of metanephric mesenchyme.
      While the ureteric bud(s) initiates, it does not elongate or branch infgfr1/2(Mes
      /-) mice. In metanephric mesenchymal rudiments, fgfr1 and fgfr2 appear to
      function downstream of Eya1 and Six1, but upstream of Six2, Sall1, and Pax2.
      Finally, this is the first example of renal aplasia in a conditional knockout
      model.

PMID- 16442092
TI  - Blood lead levels in children, China.
AB  - To evaluate Chinese children's blood lead levels (BLLs) and identify its
      distribution features, we collected articles on children's BLLs published from
      1994 to March 2004 using the Chinese Biomedical Disc and reviewed 32 articles
      eligible for the following criteria: (1) BLLs measured by Graphite Furnace Atomic
      Absorption Spectroscopy or Inductively Coupled Plasma-Mass Spectrometry; (2)
      strict quality control; (3) no lead pollution sources in the areas where the
      screened subjects live; and (4) sample size bigger than 100. We found that mean
      BLLs of Chinese children was 92.9 microg/L (37.2-254.2 microg/L), and 33.8% (9.6
      80.5%) of the subjects had BLLs higher than 100 microg/L. Nine of the 27
      provinces or cities reported had average BLLs 100 microg/L. Boys' BLL was 96.4
      microg/L, significantly higher than girls' 89.4 microg/L (P<0.001). BLLs of
      children 6 years increased with age. The mean BLLs of children living in
      industrial and urban areas were significantly higher than those of children in
      suburbs and rural areas. Our results suggested that children's BLLs in China are
      higher than those of their counterparts in other countries due to its heavy lead
      pollution. Therefore, this is of great public health importance.

PMID- 16442093
TI  - Potentiation of nicotinic currents by bradykinin in the paratracheal ganglia
      neurons of rats.
AB  - The effects of bradykinin on nicotine-induced responses were investigated in
      neurons dissociated from rat paratracheal ganglia using the nystatin-perforated
      patch-clamp recording technique. When bradykinin (10(-9) to 10(-8) M) was
      pretreated and then simultaneously applied with 10(-5) M nicotine, bradykinin
      potentiated the nicotine-induced currents. The potentiation was mimicked by
      [Hyp3]-bradykinin and inhibited by HOE-140, pertussis toxin, neomycin and U
      73122, but not U-73433. These results suggest that bradykinin potentiates
      nicotinic currents via bradykinin B2 receptor, pertussis toxin-sensitive G
      protein and phospholipase C. Since bradykinin inhibits the M-current via
      bradykinin B2 receptor and pertussis toxin-insensitive G-protein [Mochidome, T.,
      Ishibashi, H., Takahama, K., 2001. Bradykinin activates airway parasympathetic
      ganglion neurons by inhibiting M-currents. Neuroscience 105, 785-791.], it seemed
      that bradykinin B2 receptor activated two distinct signal transduction pathways
      in the paratracheal ganglia neurons. This effect of bradykinin might cause
      enhanced synaptic transmission in paratracheal ganglia neurons and contribute to
      the aggravation of pathological conditions of the lower airway via enhanced
      acetylcholine release from the postganglionic nerve terminals.

PMID- 16442094
TI  - Effect of quinpirole on striatal dopamine release and locomotor activity in
      nicotine-treated mice.
AB  - The effect of chronic oral nicotine treatment which in its intermittent delivery
      resembles human smoking was studied on the sensitivity of dopamine autoreceptors
      in mice. On the 50th day of nicotine administration in the drinking water or
      after 23-25 h withdrawal quinpirole (D2/D3 agonist, 0.01-0.1 mg/kg s.c.) was
      given, and accumbal and dorsal striatal dopamine outflow, locomotor activity and
      body temperature were measured. Dorsal striatal extracellular dopamine
      concentration and locomotor activity were found to be elevated during nicotine
      administration. Chronic nicotine did not alter the effects of small, autoreceptor
      preferring doses of quinpirole on accumbal or dorsal striatal dopamine, locomotor
      activity or body temperature. However, quinpirole's locomotor activity reducing
      effect was slightly diminished in mice treated repeatedly with nicotine (0.4
      mg/kg twice daily for 10 days s.c.). Thus, although repeated nicotine treatment
      for 5-14 days decreases dopamine autoreceptor sensitivity, after long-term oral
      nicotine treatment such a decrease is not seen. Thus, the changes occurring in
      the sensitivity of D2-like dopamine receptors probably play a minor role in
      regulating the dopaminergic transmission during long-term nicotine
      administration.

PMID- 16442095
TI  - Modulation of p-glycoprotein and breast cancer resistance protein by some
      prescribed corticosteroids.
AB  - Efflux transporters, p-glycoprotein and breast cancer resistance protein (BCRP),
      located at barrier sites such as the blood-brain barrier may affect distribution
      of steroids used for treating chronic inflammatory conditions and thus the extent
      to which they may perturb the hypothalamic-pituitary-adrenal axis. In the present
      study, six different glucocorticoids were investigated for their possible
      interactions with these efflux transporters. Beclomethasone dipropionate,
      mometasone furoate and ciclesonide active principle but not fluticasone
      propionate or triamcinolone, (all at 0.1 to 10 microM) caused inhibition of
      efflux, resulting in increased accumulation of mitoxantrone in BCRP-expressing
      MCF7/MR breast cancer cells and of calcein in p-glycoprotein-expressing SW620/R
      colon carcinoma cell. At 5 microM the same three increased sensitivity of p
      glycoprotein-expressing SW620/R to doxorubicin and stimulated ATPase activity
      associated with BCRP expressed in bacterial membrane vesicles. Budesonide also
      stimulated ATPase activity. These data demonstrate the capacity of some
      clinically used glucocorticoids to interact with efflux transporters.

PMID- 16442096
TI  - Effect of orally administered rolipram, a phosphodiesterase 4 inhibitor, on a
      mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)
      repeated application.
AB  - The purpose of this study was to evaluate the efficacy of rolipram, a
      phosphodiesterase (PDE) 4 inhibitor, in a mouse model of dermatitis induced by
      repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). BALB/c mice were
      sensitized with 0.3% w/v TNCB applied to the ear on day -7, followed by
      application three times a week from day 0. Rolipram, prednisolone and
      cyclosporine A were administered orally once daily from day 0 to 21. Rolipram at
      a dose of 10 mg/kg/day significantly inhibited the ear thickness and the increase
      in cytokine levels and enzyme activity in the ear. Interleukin (IL)-4 production
      was markedly decreased in cervical lymph node cells from animals treated with
      rolipram at a dose of 10 mg/kg/day. Prednisolone and cyclosporine A significantly
      reduced ear thickness. These compounds significantly decreased the total cell and
      lymphocyte number of the cervical lymph nodes. Furthermore, prednisolone markedly
      suppressed body weight gain, and cyclosporine A significantly increased the serum
      total IgE concentration compared with that in the vehicle-treated control.
      Rolipram, unlike prednisolone and cyclosporine A, did not influence body weight
      and the total IgE concentration in the serum. The present results suggest that
      the PDE4 inhibitor is a promising oral medicine for the treatment of chronic skin
      inflammatory diseases.

PMID- 16442097
TI  - Electrophysiological characterization of 14-benzoyltalatisamine, a selective
      blocker of the delayed rectifier K+ channel found in virtual screening.
AB  - 14-Benzoyltalatisamine is a potent and selective blocker of the delayed rectifier
      K+ channel found in a computational virtual screening study. The compound was
      found to block the K+ channel from the extracellular side. However, it is unclear
      whether 14-benzoyltalatisamine shares the same block mechanism with
      tetraethylammonium (TEA). In order to elucidate how the hit compound found by the
      virtual screening interacts with the outer vestibule of the K+ channel, the
      effects of 14-benzoyltalatisamine and TEA on the delayed rectifier K+ current of
      rat dissociated hippocampal neurons were compared using whole-cell voltage-clamp
      recording. External application of 14-benzoyltalatisamine and TEA reversibly
      inhibited the current with IC50 values of 10.1+/-2.2 microM and 1.05+/-0.21 mM,
      respectively. 14-Benzoyltalatisamine exerted voltage-dependent inhibition,
      markedly accelerated the decay of the current, and caused a significant
      hyperpolarizing shift of the steady-state activation curve, whereas TEA caused
      voltage-independent inhibition, without affecting the kinetic parameters of the
      current. The blockade by 14-benzoyltalatisamine, but not by TEA, was
      significantly diminished in a high K+ (60 mM) external solution. The potency of
      14-benzoyltalatisamine was markedly reduced in the presence of 15 mM TEA. The
      results suggest that 14-benzoyltalatisamine bind to the external pore entry of
      the delayed rectifier K+ channel with partial insertion into the selectivity
      filter, which is in conformity with that predicted by the molecular docking model
      in the virtual screening.

PMID- 16442098
TI  - The melanocortin peptide HP228 displays protective effects in acute models of
      inflammation and organ damage.
AB  - The clinically efficacious melanocortin peptide HP228 has here been investigated
      for its anti-inflammatory efficacy. In this study we have investigated the
      efficacy of HP228 in murine acute models of inflammation and myocardial
      ischaemia. Systemic treatment of mice with HP228 inhibited neutrophil
      accumulation in zymosan; urate crystal and carrageenan induced inflammatory
      models. In the urate model this was due to inhibition of pro-inflammatory
      chemokines and cytokines, whilst different mechanisms exist for zymosan
      peritonitis and carrageenan-induced air-pouch inflammation. HP228 was next
      evaluated in a model of myocardial ischaemia, another condition where cytokines
      and neutrophils are thought to play a causal role. HP228 caused a 50% reduction
      in myocardial damage following reperfusion. HP228 therefore inhibits the most
      important facet of the host inflammatory response namely leukocyte migration.
      These data show for the first time that the clinically efficacious peptide HP228
      displays protective effects in models of inflammation and organ damage.

PMID- 16442099
TI  - Making the cut: protease-mediated regulation of angiogenesis.
AB  - Angiogenesis is an integral element of normal physiologic development as well as
      of wound healing and a variety of pathologic conditions. Since the earliest
      studies of the cellular processes required for the formation of new capillaries
      from preexisting vessels, proteolysis has been recognized as one of the earliest
      and most sustained activities involved in these events. Several proteases
      including matrix metalloproteases (MMPs), and the closely related ADAM (a
      disintegrin and metalloprotease domain) and ADAMTS (a disintegrin and
      metalloprotease domain with thrombospondin motifs) families, as well as cysteine
      and serine proteases, have been implicated in this regulation. The current review
      addresses the contribution of these proteases in the positive and negative
      regulation of angiogenesis as mediated by degradation of the endothelial basement
      membrane and extracellular matrix proteins, release of angiogenic factors,
      processing of cytokines, growth factors and growth factor receptors, and the
      production of endogenous inhibitors.

PMID- 16442100
TI  - Trypanosoma rangeli: Differential expression of cell surface polypeptides and
      ecto-phosphatase activity in short and long epimastigote forms.
AB  - Trypanosoma rangeli is a parasite of a numerous wild and domestic animals,
      presenting wide geographical distribution and high immunological cross-reactivity
      with Trypanosoma cruzi, which may lead to misdiagnosis. T. rangeli has a complex
      life cycle, involving distinct morphological and functional forms in the vector.
      Here, we characterized the cell surface polypeptides and the phosphatase
      activities in short and long epimastigotes forms of T. rangeli, using intact
      living parasites. The surface protein profile revealed by the incubation of
      parasites with biotin showed a preferential expression of the 97, 70, 50, 45, 25
      22, and 15 kDa biotinylated polypeptides in the long forms, in contrast to the 55
      and 28 kDa biotinylated polypeptides synthesized by the short epimastigotes.
      Additionally, flow cytometry analysis showed that the short forms had relatively
      lower biotin surface binding than long ones. The involvement of phosphatases with
      the trypanosomatid differentiation has been proposed. In this sense, T. rangeli
      living parasites were able to hydrolyze the artificial substrate p
      nitrophenylphosphate at a rate of 25.57+/-2.03 and 10.09+/-0.93 nmol p-NPP x h(
      1) x 10(7) cells for the short and long epimastigotes, respectively. These
      phosphatase activities were linear with time for at least 60 min and the optimum
      pH lies in the acid range. Classical inhibitors of acid phosphatases, such as
      ammonium molybdate, sodium fluoride, and zinc chloride, showed a significant
      decrease in these phosphatase activities, with different patterns of inhibition.
      Additionally, these phosphatase activities presented different kinetic parameters
      (Km and Vmax) and distinct sensitivities to divalent cations. Both epimastigotes
      were unable to release phosphatase to the extracellular environment. Cytochemical
      analysis demonstrated the localization of these enzymes on the parasite surfaces
      (cell body and flagellum) and in intracellular vacuoles, resembling
      acidocalcisomes.

PMID- 16442101
TI  - Insight in eukaryotic ABC transporter function by mutation analysis.
AB  - With regard to structure-function relations of ATP-binding cassette (ABC)
      transporters several intriguing questions are in the spotlight of active
      research: Why do functional ABC transporters possess two ATP binding and
      hydrolysis domains together with two ABC signatures and to what extent are the
      individual nucleotide-binding domains independent or interacting? Where is the
      substrate-binding site and how is ATP hydrolysis functionally coupled to the
      transport process itself? Although much progress has been made in the elucidation
      of the three-dimensional structures of ABC transporters in the last years by
      several crystallographic studies including novel models for the nucleotide
      hydrolysis and translocation catalysis, site-directed mutagenesis as well as the
      identification of natural mutations is still a major tool to evaluate effects of
      individual amino acids on the overall function of ABC transporters. Apart from
      alterations in characteristic sequence such as Walker A, Walker B and the ABC
      signature other parts of ABC proteins were subject to detailed mutagenesis
      studies including the substrate-binding site or the regulatory domain of CFTR. In
      this review, we will give a detailed overview of the mutation analysis reported
      for selected ABC transporters of the ABCB and ABCC subfamilies, namely
      HsCFTR/ABCC7, HsSUR/ABCC8,9, HsMRP1/ABCC1, HsMRP2/ABCC2, ScYCF1 and P
      glycoprotein (Pgp)/MDR1/ABCB1 and their effects on the function of each protein.

PMID- 16442102
TI  - Spermidine inhibits transient and stable ribosome subunit dissociation.
AB  - Recent light-scattering experiments and sucrose density gradient centrifugational
      analyses suggested that the 70S ribosome undergoes RRF- and EF-G-triggered
      transient subunit dissociation that is followed by IF3-induced stable
      dissociation. However, the experimental conditions did not include the ubiquitous
      cellular polyamine spermidine, which is required for efficient translation. We
      found that when spermidine was present, the transient dissociation was inhibited.
      Moreover, the published experiments used ribosome concentrations that were far
      lower than the physiological concentration. We found that when spermidine and
      higher ribosome concentrations were included in the experimental conditions, only
      very limited stable subunit dissociation was observed. These results suggest that
      neither transient nor stable dissociation occurs under physiological conditions
      applied here.

PMID- 16442103
TI  - Macrophage migration inhibitory factor-deficient mice are resistant to
      ovariectomy-induced bone loss.
AB  - A link between macrophage migration inhibitory factor (MIF) and estrogen has
      recently emerged. We examined the involvement of MIF in osteoporotic changes in
      bone after ovariectomy (OVX), and revealed that MIF-deficient mice (MIF-KO) were
      completely protected from this phenomenon. The increase in osteoclast number per
      bone surface and serum IL-1beta levels, which were observed in wild-type mice
      after OVX, did not occur in MIF KO. Our data suggest that MIF plays an important
      role in the pathogenesis of postmenopausal osteoporosis, and could be a novel
      target for the treatment of this disease.

PMID- 16442104
TI  - Downregulation of protein kinase CKII is associated with cellular senescence.
AB  - Protein kinase CKII (CKII) plays a critical role in cell growth and
      proliferation. In this study, we examine how CKII activity is regulated during
      cellular senescence. Our results demonstrate that CKII activity apparently
      decreases during both replicative and H2O2-induced senescence in human diploid
      fibroblast IMR-90 cells. The mRNA and protein levels of CKIIalpha decreases
      significantly during replicative and H2O2-induced senescence, while only slight
      reduction in those of CKIIbeta is observed during replicative senescence.
      Treatment of IMR-90 cells with CKII inhibitors 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole and apigenin led cells to acquire a senescent
      phenotype as judged by the senescence-associated beta-galactosidase marker and
      overexpression of p53 and p21(Waf-1). Knockdown of CKIIalpha in IMR-90 cells by
      RNA interference also dramatically induced the senescent phenotype. In parallel,
      CKII activity was transcriptional downregulated in rat liver and testis with
      advancing age. Taken together, these results suggest that downregulation of CKII
      activity is tightly associated not only with cellular senescence but also with
      organism aging.

PMID- 16442105
TI  - Endogenous macrophage migration inhibitory factor modulates glucocorticoid
      sensitivity in macrophages via effects on MAP kinase phosphatase-1 and p38 MAP
      kinase.
AB  - The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) is
      induced by glucocorticoids (GCs), but it was not previously known if MIF
      regulates cellular sensitivity to GC. Here we show in GC and LPS-treated
      peritoneal macrophages derived from MIF-/- and wt mice that the absence of
      endogenous MIF is associated with increased sensitivity to GC of TNF release.
      This is associated with increased expression of mitogen-activated protein kinase
      (MAPK) phosphatase-1 (MKP-1), concomitant decreased phosphorylation of p38 MAPK,
      but no effect of MIF on nuclear factor kappaB (NF-kappaB). These results
      demonstrate that MIF regulates GC sensitivity by phosphorylation of p38, and
      provides a cellular mechanism for this observation, indicating that MKP-1 is a
      central target of this regulation.

PMID- 16442106
TI  - Characterization of severe acute respiratory syndrome coronavirus membrane
      protein.
AB  - The coronavirus membrane protein (M) is the key player in the assembly of virions
      at intracellular membranes between endoplasmic-reticulum and Golgi-complex. Using
      a newly established human monoclonal anti-M antibody we detected glycosylated and
      nonglycosylated membrane-associated M in severe acute respiratory syndrome
      associated coronavirus (SARS-CoV) infected cells and in purified virions. Further
      analyses revealed that M contained a single N-glycosylation site at asparagine 4.
      Recombinant M was transported to the plasma membrane and gained complex-type N
      glycosylation. In SARS-CoV infected cells and in purified virions, however, N
      glycosylation of M remained endoglycosidase H-sensitive suggesting that trimming
      of the N-linked sugar side chain is inhibited.

PMID- 16442107
TI  - Metabolic engineering of coenzyme Q by modification of isoprenoid side chain in
      plant.
AB  - Coenzyme Q (CoQ), an electron transfer molecule in the respiratory chain and a
      lipid-soluble antioxidant, is present in almost all organisms. Most cereal crops
      produce CoQ9, which has nine isoprene units. CoQ10, with 10 isoprene units, is a
      very popular food supplement. Here, we report the genetic engineering of rice to
      produce CoQ10 using the gene for decaprenyl diphosphate synthase (DdsA). The
      production of CoQ9 was almost completely replaced with that of CoQ10, despite the
      presence of endogenous CoQ9 synthesis. DdsA designed to express at the
      mitochondria increased accumulation of total CoQ amount in seeds.

PMID- 16442108
TI  - Steroid hormone mediation of limbic brain plasticity and aggression in free
      living tree lizards, Urosaurus ornatus.
AB  - The neural mechanisms by which steroid hormones regulate aggression are unclear.
      Although testosterone and its metabolites are involved in both the regulation of
      aggression and the maintenance of neural morphology, it is unknown whether these
      changes are functionally related. We addressed the hypothesis that parallel
      changes in steroid levels and brain volumes are involved in the regulation of
      adult aggression. We examined the relationships between seasonal hormone changes,
      aggressive behavior, and the volumes of limbic brain regions in free-living male
      and female tree lizards (Urosaurus ornatus). The brain nuclei that we examined
      included the lateral septum (LS), preoptic area (POA), amygdala (AMY), and
      ventromedial hypothalamus (VMH). We showed that the volumes of the POA and AMY in
      males and the POA in females vary with season. However, reproductive state (and
      thus hormonal state) was incompletely predictive of these seasonal changes in
      males and completely unrelated to changes in females. We also detected male
      biased dimorphisms in volume of the POA, AMY, and a dorsolateral subnucleus of
      the VMH but did not detect a dimorphism between alternate male morphological
      phenotypes. Finally, we showed that circulating testosterone levels were higher
      in males exhibiting higher frequency and intensity of aggressive display to a
      conspecific, though brain nucleus volumes were unrelated to behavior. Our
      findings fail to support our hypothesis and suggest instead that plasma
      testosterone level covaries with aggression level and in a limited capacity with
      brain nucleus volumes but that these are largely unrelated relationships.

PMID- 16442109
TI  - Functional outcome following treatment of transolecranon fracture-dislocation of
      the elbow.
AB  - Elbow fracture-dislocations are considered as difficult injuries to treat.
      Anterior olecranon fracture-dislocation consist an uncommon pattern which is
      likely to be under-diagnosed. Eight patients identified as anterior fracture
      dislocation of the elbow were retrospectively reviewed. There were seven men and
      one woman with an average age of 35 years (range, 22-58 years). Proximal ulna
      fracture was comminuted in seven and simple oblique in one patient. Associated
      fractures were of coronoid in four and radial head in two. Reconstruction plate
      was used in seven patients and tension band wiring in just one. Nevertheless,
      tension wiring failed and was successfully revised to plate fixation combined
      with bone graft. Patients were followed for an average of 37.4 months (range, 10
      50 months). The end results were two excellent, five good and one fair, based on
      Broberg and Morrey scale. An average score of 89 points was obtained using
      American Shoulder and Elbow Surgeons elbow scoring system. Treatment of anterior
      olecranon fracture dislocation is mostly satisfactory if contour and dimension of
      greater sigmoid notch is accurately restored.

PMID- 16442112
TI  - Improving availability of EmOC services in Rwanda--CARE's experiences and lessons
      learned at Kabgayi Referral Hospital.
AB  - OBJECTIVE: CARE's work in Rwanda was designed to improve the functional capacity
      of health facilities for the delivery of EmOC services. METHODS: The project
      supported a comprehensive package of focused interventions that included hospital
      renovations, provision of essential equipment, training of staff and improvement
      of management systems at the Kabgayi regional referral hospital. RESULTS: There
      was an increased level of preparedness for emergencies and ability to manage
      common obstetric complications according to evidence-based practices. These
      changes ultimately led to increased availability, quality and use of services as
      demonstrated by an increase in the demand for care of obstetric complications at
      the facility. The met need increased from 16% at the start of the project (2001)
      to 25% in 2004, while the cesarean rate remained essentially the same (1.9% and
      3.2%) over the same time period. There were progressive declines in the case
      fatality rates from 2.2% in 2001 to 1.2% in 2004. CONCLUSION: CARE's experience
      indicates that progress towards reducing maternal mortality requires specific
      efforts that support and strengthen existing health systems to provide skilled
      care that can save women's lives.

PMID- 16442113
TI  - Strengthening emergency obstetric care in Ayacucho, Peru.
AB  - OBJECTIVE: With support from the Averting Maternal Death and Disability (AMDD)
      Program, CARE began the FEMME Project in 2000 to increase access and utilization
      of emergency obstetric care (EmOC) services for the approximately 48,000 pregnant
      women in the northern provinces of Ayacucho. METHODS: The project targeted 5
      facilities with a comprehensive package of interventions designed to improve
      capacity to provide quality EmOC services and to promote a human rights approach
      in health care. Key program activities included improvements in infrastructure,
      human resources capacity development, development of service standards and
      protocols, quality improvement activities, and promoting a rights-based approach
      to health. RESULTS: By the end of the project, northern Ayacucho had 6
      functioning EmOC facilities: 3 comprehensive (including a non-FEMME project
      facility) and 3 basic. This exceeds the UN minimum recommendation of 5 EmOC
      facilities per 500,000 population. Other changes in the UN process indicators
      indicate an increase in quality and utilization of EmOC services. Met need for
      EmOC increased significantly from 30% in 2000 to a high of 84% in 2004. Case
      fatality rates declined and the number of maternal deaths in the entire region
      declined. CONCLUSION: CARE's work in Ayacucho made an impact on policies and
      programs related to EmOC throughout the region. Within CARE, project experiences
      have supported maternal health programs particularly in the Latin
      American/Caribbean region.

PMID- 16442111
TI  - Measurement of the pubic portion of the levator ani muscle in women with
      unilateral defects in 3-D models from MR images.
AB  - OBJECTIVE: Develop a method to quantify the cross-sectional area of the pubic
      portion of the levator ani muscle, validate the method in women with unilateral
      muscle defects, and report preliminary findings in those women. METHOD: Multi
      planar proton density magnetic resonance images of 12 women with a unilateral
      defect in the pubic portion of their levator ani were selected from a larger
      study of levator ani muscle anatomy in women with and without genital prolapse.
      Three-dimensional bilateral models of the levator ani were reconstructed (using 3
      D Slicer, version 2.1b1) and divided into iliococcygeal and pubic portions.
      Muscle cross-sectional areas were calculated at four equally spaced locations
      perpendicular to a line drawn from the pubic origin to the visceral insertion
      using the I-DEAS computer modeling software. RESULTS: The cross-sectional area of
      the muscle on the side with the defect was smaller than the normal side at all
      the four locations. The average bilateral difference was up to 81% at location 1
      (nearest pubic origin). Almost all of the volume difference (13.7%, P=0.0004) was
      attributable to a reduction in the pubic portion (24.6%, P<0.0001), not the
      iliococcygeal portion (P=0.64), of the muscle. CONCLUSIONS: A method was
      developed to quantify cross-sectional area of the pubic portion of the levator
      ani perpendicular to the intact muscle direction. Significant bilateral cross
      sectional area differences were found between intact and defective muscles in
      women with a unilateral defect.

PMID- 16442114
TI  - Randomized trial of hormone therapy in women after coronary bypass surgery.
      Evidence of differential effect of hormone therapy on angiographic progression of
      disease in saphenous vein grafts and native coronary arteries.
AB  - Clinical trials indicate that hormone therapy (HT) does not decrease
      cardiovascular disease events or angiographic coronary disease progression. The
      effects of HT on SVG vessels are unknown. To determine whether postmenopausal
      hormone therapy started after coronary bypass surgery (CABG) decreases saphenous
      vein graft (SVG) disease, we conducted a multicenter randomized placebo
      controlled angiographic study of estradiol+/-medroxyprogesterone started within 6
      months of CABG in 83 postmenopausal women. Angiographic and intravascular
      ultrasound (IVUS) assessment at 6 and 42 months was planned to assess SVG disease
      progression. The study was stopped early following publication of the Women's
      Health Initiative Estrogen/Progestin study. Eighty-three subjects underwent a 6
      month angiogram with 63 undergoing IVUS. Forty-five subjects completed the 42
      month angiogram (20 underwent 42-month IVUS). In analysis of paired 6- and 42
      month angiogram and IVUS studies, HT slowed angiographic progression of SVG
      disease assessed by mean percent stenosis (p<0.001), minimal lumen diameter
      (p=0.029), and total plaque volume (p=0.006). In contrast, HT accelerated disease
      progression in non-bypassed native coronary arteries (minimum lumen diameter,
      p=0.01). SVG disease and closure occurred in 38% subjects within 1-year post
      CABG. The groups had similar frequency of cardiovascular events expect for
      angioplasty that occurred in eight HT compared to one placebo subject (p<0.05).
      In HT subjects angioplasty was indicated for native coronary arterial stenoses
      while in the placebo subject angioplasty was indicated for SVG stenosis. This
      study suggests that hormone treatment may slow SVG disease progression while
      accelerating atherosclerosis in non-bypassed native coronary arteries.

PMID- 16442117
TI  - High-performance liquid chromatography of lactose with evaporative light
      scattering detection, applied to determine fine particle dose of carrier in dry
      powder inhalation products.
AB  - A method for quantification of the fine particle dose of lactose is described,
      using a hydrophilic interaction chromatography (HILIC) method and evaporative
      light scattering detection. The HILIC method used an aminopropyl column and a
      mobile phase consisting of acetonitril/water (80/20, v/v) for isocratic elution.
      Sensitive chromatography was obtained using a low concentration of water in the
      extraction solvent. The detection limit (RSD<10%) at an injection volume of 10
      microL is 10 microg/mL. Linearity was obtained in the range of 10-80 microg/mL
      (R(2)>0.99). A relative standard deviation (RSD) of 0.5% (N=6) demonstrated good
      precision of the optimized method.

PMID- 16442115
TI  - Perilipin, a potential substitute for adipophilin in triglyceride storage in
      human macrophages.
AB  - Abnormal lipid deposition in human arteries leads to the formation of fatty
      streaks due to the accumulation of a large number of macrophage derived-foam
      cells. The formation and catabolism of intracellular lipid droplets is regulated
      by droplet-associated proteins. Among such proteins, the role of perilipin in
      human macrophages was unknown. In this study, we first showed that perilipin
      expression was increased during differentiation of human monocytes to
      macrophages. Interestingly, cellular perilipin content was unaffected by
      treatment of cells with OxLDL, AcLDL, VLDL or sterol esters. Moreover, its
      expression was not dependent on the presence of adipophilin, another lipid
      droplet-associated protein, since it was not affected by transfection of
      macrophages with siRNA-adipophilin. Perilipin overexpression in macrophages with
      an expression vector resulted in significant lipid droplet formation and TG
      accumulation and this was unaffected by decreasing adipophilin levels using
      siRNA. Consequently, perilipin, like adipophilin, might play an important role in
      the conversion of macrophages into foam cells and contribute to lesion formation.
      Therefore, inhibition of adipophilin might not be sufficient to prevent lesion
      formation as previously suggested, and perilipin inhibition might be additionally
      required.

PMID- 16442116
TI  - Adiponectin is a candidate marker of metabolic syndrome in obese children and
      adolescents.
AB  - The aim of this study was to compare the use of several biomarkers to identify
      obese children and adolescents with increased metabolic risk. One hundred sixty
      two Caucasian obese children and adolescents (41% males, 9-18 years old) referred
      to the Istituto Auxologico Italiano between 2003 and 2004 underwent an oral
      glucose tolerance test. Circulating levels of adiponectin (AD), plasminogen
      activator inhibitor 1 (PAI-1), interleukin 18 (IL-18), C-reactive protein (CRP),
      fibrinogen, uric acid, lipids and insulin were measured. Twenty five percent of
      obese children had the MS defined using World Health Organization-derived child
      specific criteria. MS subjects had significantly lower AD (p<0.01) and higher log
      PAI-1 (p<0.001), uric acid (p<0.0001), and IL-18 (p<0.001). Subjects with AD
      levels </=median value had a significantly increased risk of having the MS
      (p<0.0001), as did subjects with uric acid and PAI-1 levels greater than the
      median. There was no increased risk with elevated IL-18, CRP, or fibrinogen.
      Hypoadiponectinemia was independently associated with the MS risk (p<0.0001). In
      conclusion in obese children and adolescents AD is the best predictor of MS and
      thus of higher cardiovascular disease risk.

PMID- 16442118
TI  - Separation and determination of basic dyes formulated in hair care products by
      capillary electrophoresis.
AB  - A capillary electrophoretic (CE) method for analyzing five basic dyes (Basic Red
      76, Basic Brown 16, Basic Yellow 57, Basic Brown 17 and Basic Blue 99) sold under
      the trade name Arianor, which are commonly used in hair care products, has been
      established. A buffer of 100 mM acetic acid-ammonium acetate (50:50) containing
      90% (v/v) methanol was employed in a fused-silica capillary of 40.0 cm x 50
      microm I.D. with a bubble cell arrangement. Washing the capillary end immediately
      after injection was effective in preventing peak tailing of the basic dyes, which
      was due to their adsorption onto the outer wall of the capillary during the
      injection. Under these optimized conditions, acceptable results for
      reproducibility, limit of detection and quantitation, and linearity were obtained
      for the five authentic dyes tested. The recoveries of five authentic basic dyes
      spiked to three commercial hair care products also provided with acceptable
      results. This optimized CE method is useful for the analysis of mixed basic dyes
      in hair care products.

PMID- 16442119
TI  - Suitability of solid-phase microextraction for the determination of
      organophosphate flame retardants and plasticizers in water samples.
AB  - The feasibility of solid-phase microextraction (SPME) for the determination of
      several organophosphorus flame retardants and plastizicers in water samples by
      gas chromatography-nitrogen phosphorous detection (GC-NPD) is evaluated. These
      compounds have a wide range of polarities and volatilities and require a thorough
      optimisation of the different SPME parameters. Considering also possible
      contamination and carryover sources, the best compromise microextraction
      conditions were found to be direct extraction of 22 ml samples, containing 300
      mg/ml of NaCl, with a PDMS-DVB coated fibre at room temperature. Although
      equilibrium was not achieved, an extraction time of 40 min allowed obtaining a
      good sensitivity (quantification limits between 0.010 and 0.025 ng/ml),
      comparable to that achieved by solid-phase extraction (SPE) of 1l samples,
      producing both similar values of precision and accuracy. Furthermore, the SPME
      method has shown to be free of matrix effects, avoiding the need of employing the
      standard addition procedure for quantification, and was suitable for the
      determination of eight of the nine considered compounds. Only tris-(2-ethylhexyl)
      phosphate was neither determinable by SPME nor by SPE. Finally, the application
      of the developed methodology to the analysis of wastewater samples, showed that
      important concentrations of these compounds (up to 10 ng/ml) have been detected
      in treated sewage water, being discharged into the aquatic environment.

PMID- 16442120
TI  - Breakthrough curves and elution profiles of single solutes in case of adsorption
      isotherms with two inflection points.
AB  - The shape of breakthrough curves and elution profiles depends strongly on the
      course of the specific equilibrium functions characterizing the chromatographic
      system. For a highly efficient system the equilibrium theory provides a
      methodology how to predict the band profiles. The concept is frequently applied
      to analyze single component systems characterized by isotherms possessing simple
      shapes (Langmuir or anti-Langmuir behaviour). However, adsorption isotherms often
      possess more complicated shapes and have inflection points in their courses. This
      leads to the development of composite concentration waves and results in complex
      shapes of breakthrough curves and elution profiles. In this paper, the
      equilibrium theory is used to predict breakthrough curves for a chromatographic
      system characterized by an adsorption isotherm with two inflection points. The
      results obtained are validated by comparing with numerical solutions of the
      equilibrium dispersive model.

PMID- 16442121
TI  - Synthesis of highly monodisperse polystyrene microspheres via dispersion
      polymerization using an amphoteric initiator.
AB  - The highly monodisperse polystyrene (PS) microspheres were produced by dispersion
      polymerization using an amphoteric initiator, 2,2'-azobis [N-(2-carboxyethyl)-2-2
      methylpropionamidine] (VA-057). The polymerization characteristics were
      investigated and compared with conventional initiators, 2,2
      azobis(isobutyronitrile) (AIBN) and benzoyl peroxide (BPO). The monodisperse PS
      microspheres having the coefficient of variation (C(v)) of diameter all less than
      4% are obtained at very low stabilizer, poly(vinyl pyrrolidone) (PVP)
      concentrations of 1 and 2 wt%. It is found that the size dependence of the VA-057
      system, D(n) proportional, variant [VA-057](0.267), is less sensitive than a
      conventional initiator system. When the same amount, 2 wt%, of AIBN, BPO, and VA
      057 is used under the identical PVP concentration of 2 wt%, the D(n)/C(v)'s are
      1.95/11.57, 1.47/22.44, and 2.08 microm/2.50%, respectively. The uniformity of
      particles was characterized employing an optical analyzer, Turbiscan. For the VA
      057 system, the back scattering intensity is linearly reduced with time having a
      constant sedimentation rate of 48.98 microm/min throughout the settling process.
      The uniformity of PS particles in the VA-057 system stems from (1) the higher
      rate of polymerization in early stage of polymerization, followed by
      significantly faster reduction of the rate, and (2) good dispersion stability of
      primary particles. Therefore, it is found that the use of an amphoteric
      initiator, VA-057, is promising for producing monodisperse particles in
      dispersion polymerization.

PMID- 16442122
TI  - A fibrillin-1-fragment containing the elastin-binding-protein GxxPG consensus
      sequence upregulates matrix metalloproteinase-1: biochemical and computational
      analysis.
AB  - Mutations in the gene for fibrillin-1 cause Marfan syndrome (MFS), a common
      hereditary disorder of connective tissue. Recent findings suggest that
      proteolysis, increased matrix metalloproteinase activity, and fragmentation of
      fibrillin-rich microfibrils in tissues of persons with MFS contribute to the
      complex pathogenesis of this disorder. In this study we show that a fibrillin-1
      fragment containing a EGFEPG sequence that conforms to a putative GxxPG elastin
      binding protein (EBP) consensus sequence upregulates the expression and
      production of matrix metalloproteinase (MMP)-1 by up to ninefold in a cell
      culture system. A mutation of the GxxPG consensus sequence site abrogated the
      effects. This is the first demonstration of such an effect for ligands other than
      elastin fragments. Molecular dynamics analysis of oligopeptides with the wildtype
      and mutant sequence support our biochemical results by predicting significant
      alterations of structural characteristics such as the potential for forming a
      type VIII beta-turn that are thought to be important for binding to the EBP.
      These results suggest that fibrillin-1 fragments may regulate MMP-1 expression,
      and that the dysregulation of MMPs related to fragmentation of fibrillin might
      contribute to the development of MFS. Our Gene Ontology (GO) analysis of the
      human proteome shows that proteins with multiple GxxPG motifs are highly enriched
      for GO terms related to the extracellular matrix. Matrix proteins with multiple
      GxxPG sites include fibrillin-1, -2, and -3, elastin, fibronectin, laminin, and
      several tenascins and collagens. Some of these proteins have been associated with
      disorders involving alterations in MMP regulation, and the results of the present
      study suggest a potential mechanism for these observations.

PMID- 16442123
TI  - Dementia in the Greco-Roman world.
AB  - Greek and Roman physicians developed distinct and detailed ideas, which can be
      regarded as early versions of our modern concept of dementia. Several classical
      sources--some of them medical--offer intriguing descriptions of many cognitive
      and behavioral symptoms in dementia, which are currently used for diagnostic
      purposes. Limitations of this ancient concept are due to terminological and
      epidemiological factors, but also to the physicians' social role. Only a small
      part of this early literature is cited in contemporary work on the origin of the
      dementia concept, which can be clearly traced back to the Age of Enlightenment
      and whose earlier history still needs to be elucidated.

PMID- 16442124
TI  - Growing biological networks: beyond the gene-duplication model.
AB  - In this paper we propose a generalized growth model for biological interaction
      networks, including a set of biological features which have been inspired by a
      long tradition of simulations of immune system and chemical reaction networks. In
      our models we include characteristics such as the heterogeneity of biological
      nodes, the existence of natural hubs, the nodes binding by mutual affinity and
      the significance of type-based networks as compared with instance-based networks.
      Under these assumptions, we analyse the importance of the nodes concentration
      with respect to the selection of incoming nodes. We show that networks with fat
      tailed degree distribution and highly clustered structure naturally emerge in
      systems possessing certain properties: new instances need to be produced through
      an endogenous source and this source needs to provide a positive feedback
      favouring nodes with high concentration to receive new connections. Furthermore,
      we show that understanding the concentration dynamics of each node and the
      consequent correlation between connectivity and concentration is a more adequate
      way to capture the global properties of type-based biological networks.

PMID- 16442125
TI  - Probabilistic settling in the Local Exchange Model of turbulent particle
      transport.
AB  - The Local Exchange Model (LEM) is a stochastic diffusion model of particle
      transport in turbulent flowing water. It was developed mainly for application to
      particles of near-neutral buoyancy that are strongly influenced by turbulent
      eddies. Turbulence can rapidly transfer such particles to the bed, where
      settlement can then occur by, for example, sticking to biofilms (e.g., fine
      particulate organic matter, or FPOM) or attaching to the substrate behaviorally
      (e.g., benthic invertebrates). Previous papers on the LEM have addressed the
      problems of how long (time) and far (distance) a suspended particle will be
      transported before hitting the bed for the first time. These are the hitting-time
      and hitting-distance problems, respectively. Hitting distances predicted by the
      LEM for FPOM in natural streams tend to be much shorter than the distances at
      which most particles actually settle, suggesting that particles usually do not
      settle the first time they hit the bed. The present paper extends the LEM so it
      can address probabilistic settling, where a particle encountering the bed can
      either remain there for a positive length of time (i.e., settle) or immediately
      reflect back into the water column, each with positive probability. Previous
      results for the LEM are generalized by deducing a single set of equations
      governing the probability distribution and moments of a broad class of quantities
      that accumulate during particle trajectories terminated by hitting or settling on
      the bed (e.g., transport time, transport distance, cumulative energy expenditure
      during transport). Key properties of the settling-time and settling-distance
      distributions are studied numerically and compared with the observed FPOM
      settling-distance distribution for a natural stream. Some remaining limitations
      of the LEM and possible means of overcoming them are discussed.

PMID- 16442126
TI  - Self-other organization: why early life did not evolve through natural selection.
AB  - The improbability of a spontaneously generated self-assembling molecule has
      suggested that life began with a set of simpler, collectively replicating
      elements, such as an enclosed autocatalytic set of polymers (or protocell). Since
      replication occurs without a self-assembly code, acquired characteristics are
      inherited. Moreover, there is no strict distinction between alive and dead; one
      can only infer that a protocell was alive if it replicates. These features of
      early life render natural selection inapplicable to the description of its change
      of-state because they defy its underlying assumptions. Moreover, natural
      selection describes only randomly generated novelty; it cannot describe the
      emergence of form at the interface between organism and environment. Self
      organization is also inadequate because it is restricted to interactions amongst
      parts; it too cannot account for context-driven change. A modified version of
      selection theory or self-organization would not work because the description of
      change-of-state through interaction with an incompletely specified context has a
      completely different mathematical structure, i.e. entails a non-Kolmogorovian
      probability model. It is proposed that the evolution of early life is
      appropriately described as lineage transformation through context-driven
      actualization of potential (CAP), with self-organized change-of-state being a
      special case of no contextual influence, and competitive exclusion of less fit
      individuals through a selection-like process possibly (but not necessarily)
      playing a secondary role. It is argued that natural selection played an important
      role in evolution only after genetically mediated replication was established.

PMID- 16442127
TI  - Effect of peripheral administration of leptin on the renal sympathetic nerve
      activity in high-fat diet-related hypertensive rats.
AB  - A previous study of ours demonstrated that a high-fat diet (FAT) causes body fat
      accumulation, as well as elevation of plasma leptin level, renal sympathetic
      nerve activity (RSNA), and blood pressure (BP). In the study reported here, we
      analyzed the role of leptin in these elevations of the RSNA and BP due to FAT
      feeding by assessing sympathetic and cardiovascular responses to intravenous (IV)
      administration of leptin in rats fed either a FAT or a high-carbohydrate diet
      (CHO). The results showed that baseline body fat, plasma leptin level, RSNA and
      BP were significantly higher in the FAT group than in the CHO group, and that IV
      administration of leptin elevated RSNA and plasma leptin levels but lowered BP in
      the CHO group. However, these effects of leptin were eliminated in the FAT group.
      These findings suggest that FAT-fed rats which expose basal elevation of plasma
      leptin levels, RSNA and BP might be hyposensitive to endogenous leptin.
      Therefore, leptin resistance appeared obviously in FAT-induced hypertension might
      indicate that leptin is implicated in generating the elevation of RSNA and BP
      induced by long-term FAT feeding.

PMID- 16442128
TI  - Effect of chronic psychological stress on insulin release from rat isolated
      pancreatic islets.
AB  - Despite documented studies, the exact role of stress on diabetes is still
      unclear. The present study investigates the effect of chronic psychological
      stress on insulin release from isolated rat pancreatic islets. Male Wistar rats
      were divided into two groups of control and stressed (n=8/group). The animals of
      the stressed group were exposed to restraint stressors (1 h twice daily) for 15
      or 30 consecutive days. At the beginning and end of the experimental periods, the
      animals were weighed and blood samples taken to determine the fasting plasma
      levels of glucose, insulin and corticosterone. On the following day the
      pancreatic islets of 5/group of the above animals were isolated and the static
      release of insulin in the presence of different glucose concentrations (2.8, 5.6,
      8.3, 16.7 mM) was assessed. The results showed that in the stressed group,
      fasting plasma glucose levels were increased significantly on the 15th day as
      compared to the control group. However there was no significant increase on the
      30th day. Fasting plasma insulin was significantly decreased on the 15th and 30th
      days of the experiment in the stressed group. Stressed rats showed significantly
      higher fasting plasma corticosterone levels, only on the 15th day, as compared to
      the control rats. In response to increasing concentrations of glucose, insulin
      release from islets of the stressed group was increased significantly on the 30th
      day of the experiment as compared to the control group. We conclude that chronic
      psychological stress could increase responsiveness of pancreatic beta cells to
      glucose, in vitro, and thus, low insulin levels of the stressed animals, in vivo,
      may be due to reason(s) other than the reduction of insulin releasing capacity of
      pancreatic beta cells.

PMID- 16442129
TI  - Protective effect of anthocyanins in middle cerebral artery occlusion and
      reperfusion model of cerebral ischemia in rats.
AB  - Ischemic stroke results from a transient or permanent reduction in cerebral blood
      flow that is restricted to the territory of a major brain artery. The major
      pathobiological mechanisms of ischemia/reperfusion injury include excitotoxicity,
      oxidative stress, inflammation, and apoptosis. In the present report, we first
      investigated the protective effects of anthocyanins against focal cerebral
      ischemic injury in rats. The pretreatment of anthocyanins (300 mg/kg, p.o.)
      significantly reduced the brain infarct volume and a number of TUNEL positive
      cells caused by middle cerebral artery occlusion and reperfusion. In the
      immunohistochemical observation, anthocyanins remarkably reduced a number of
      phospho-c-Jun N-terminal kinase (p-JNK) and p53 immunopositive cells in the
      infarct area. Moreover, Western blotting analysis indicated that anthocyanins
      suppressed the activation of JNK and up-regulation of p53. Thus, our data
      suggested that anthocyanins reduced neuronal damage induced by focal cerebral
      ischemia through blocking the JNK and p53 signaling pathway. These findings
      suggest that the consumption of anthocyanins may have the possibility of
      protective effect against neurological disorders such as brain ischemia.

PMID- 16442130
TI  - MDR- and CYP3A4-mediated drug-herbal interactions.
AB  - According to recent epidemiological reports, almost 40% of American population
      use complimentary and alternative medicine (CAM) during their lifetime. Patients
      detected with HIV or cancer often consume herbal products especially St. John's
      wort (SJW) for antidepressants in combination with prescription medicines. Such
      self-administered herbal products along with prescribed medicines raise concerns
      of therapeutic activity due to possible drug-herbal interactions. P-glycoprotein
      (P-gp) and cytochrome P450 3A4 (CYP3A4) together constitute a highly efficient
      barrier for many orally absorbed drugs. Available literature, clinical reports
      and in vitro studies from our laboratory indicate that many drugs and herbal
      active constituents are substrates for both P-gp and CYP3A4. Results from
      clinical studies and case reports indicate that self-administered SJW reduce
      steady state plasma concentrations of amitriptyline, cyclosporine, digoxin,
      fexofenadine, amprenavir, indonavir, lopinavir, ritonavir, saquinavir,
      benzodiazepines, theophyline, irinotecan, midazolan and warfarin. This herbal
      agent has been also reported to cause bleeding and unwanted pregnancies when
      concomitantly administered with oral contraceptives. Most of these medicinal
      agents and SJW are substrates for P-gp and/or CYP3A4. In vitro studies from our
      laboratory suggest that short-term exposure with pure herbal agents such as
      hypericin, kaempferol and quercetin or extract of SJW resulted in higher uptake
      or influx of ritonavir and erythromycin. Hypericin, kaempferol and quercetin also
      caused a remarkable inhibition of cortisol metabolism with the percent intact
      cortisol values of 64.58%, 89.6% and 90.1%, respectively, during short-term in
      vitro experiments. Conversely, long-term exposure of herbal agents (hyperforin,
      kaempferol and quercetin) showed enhanced expression of CYP3A4 mRNA in Caco-2
      cells. In another study, we observed that long-term exposure of hypericin,
      kaempferol, quercetin and silibinin resulted in higher MDR-1 mRNA expression in
      Caco-2 cells. Therefore, herbs can pharmacokinetically act as inhibitors or
      inducers. Medicinal agents that are substrates P-gp-mediated efflux and/or CYP
      mediated metabolism are likely to be potential candidates for drug-herbal
      interactions. The duration of exposure of cells/healthy volunteers/animals to
      herbals appears to be critical for drug-herbal interaction. An increase in plasma
      drug concentration is possible during concomitant administration of SJW and
      prescribed drugs. In contrast, prolonged intake of herbal supplement followed by
      drug administration may result in subtherapeutic concentrations. Therefore,
      clinical implications of such drug herbal interactions depend on a variety of
      factors such as dose, frequency and timing of herbal intake, dosing regimen,
      route of drug administration and therapeutic range. In vitro screening techniques
      will play a major role in identifying possible herb-drug interactions and thus
      create a platform for clinical studies to emerge. Mechanisms of drug-herbal
      interaction have been discussed in this review article.

PMID- 16442131
TI  - Survey on germination and species composition of dinoflagellates from ballast
      tanks and recent sediments in ports on the South Coast of Finland, North-Eastern
      Baltic Sea.
AB  - Cyst beds in ships and ports in Finland have previously been unstudied.
      Therefore, sediments from ships' ballast water tanks and four Finnish ports were
      sampled for dinoflagellate cysts and other phytoplankton. Untreated sediments
      were incubated at 10 degrees C and 20 degrees C in the local 6 psu salinity for
      1, 4 and 7 days, and vegetative cells were examined with light and scanning
      electron microscope. Sediments were inhabited by various dinoflagellates,
      diatoms, chlorophytes, cyanophytes and small flagellates. Germinated
      dinoflagellates were found in 90% of ballast tanks and in all ports.
      Gymnodiniales spp. and Heterocapsa rotundata formed a major proportion of the
      proliferating dinoflagellate cells. One species, Peridinium quinquecorne, not
      previously reported from the Baltic Sea, was identified with SEM. The study
      emphasises that ships are potential transport vehicles for dinoflagellate cysts
      even in the low salinity Finnish waters, and small-sized dinoflagellates should
      be focused upon in ballast water studies.

PMID- 16442132
TI  - The Humber Estuary, Eastern England: Strategic planning of flood defences and
      habitats.
AB  - The Humber Estuary Shoreline Management Plan provides a long-term strategy for
      investment in sustainable defences to reduce the risk to people and property from
      flooding in part of Eastern England. In addition to the estuary's economic
      importance with its ports, industry and the third of a million people living on
      its floodplain, the Humber is of outstanding value for wildlife and its historic
      environment. The plan has to meet the needs of these activities and take account
      of rising sea level. It is based on extensive technical studies and modelling.
      The realignment of some embankments is being examined so that the creation of
      intertidal habitat will offset losses from coastal squeeze, increase the
      stability for some lengths of embankment and reduce extreme high flood levels in
      the tidal rivers. The 80 ha Paull Holme Strays managed realignment wetland was
      completed in the summer of 2003 and work is in progress on another at Alkborough.
      Other such realignment will be developed as part of the implementation of the
      long term strategy.

PMID- 16442133
TI  - Antihyperalgesic effects of local injections of anandamide, ibuprofen, rofecoxib
      and their combinations in a model of neuropathic pain.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit fatty acid amidohydrolase
      (FAAH), the enzyme responsible for the metabolism of anandamide, an
      endocannabinoid. The analgesic interactions between anandamide (0.01 microg),
      ibuprofen (0.1 microg) and rofecoxib (0.1 microg) or their combinations
      administered locally in the hind paw of neuropathic rats were investigated
      together with the effects of specific antagonists for the cannabinoid CB(1)
      (AM251; 80 microg) and CB(2) (AM630; 25 microg) receptors. Mechanical allodynia
      and thermal hyperalgesia were evaluated in 108 Wistar rats allocated to: (1-4)
      NaCl 0.9%; anandamide; ibuprofen; rofecoxib; (5-6) anandamide+ibuprofen or
      rofecoxib; (7-8) AM251 or AM630; (9-10) anandamide+AM251 or AM630; (11-12)
      ibuprofen+AM251 or AM630; (13-14) rofecoxib+AM251 or AM630; (15-16)
      anandamide+ibuprofen+AM251 or AM630; (17-18) anandamide+rofecoxib+AM251 or AM630.
      Drugs were given subcutaneously in the hind paw 15min before pain tests.
      Anandamide, ibuprofen, rofecoxib and their combinations significantly decreased
      mechanical allodynia and thermal hyperalgesia with an ED(50) of 1.6+/-0.68ng and
      1.1+/-1.09 ng for anandamide, respectively. The effects of NSAIDs were not
      antagonized by AM251 or AM630 but those of anandamide were inhibited by AM251 but
      not by AM630. In conclusion, locally injected anandamide, ibuprofen, rofecoxib
      and their combinations decreased pain behavior in neuropathic animals. Local use
      of endocannabinoids to treat neuropathic pain may be an interesting way to treat
      this condition without having the deleterious central effects of systemic
      cannabinoids.

PMID- 16442134
TI  - Transforming growth factor-alpha induces sex-specific neurochemical imbalance in
      the stress- and memory-associated brain structures.
AB  - Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many
      developmental processes. However, its role in adult nervous system is yet
      unclear. Studies have shown that TGFalpha can regulate stress and memory behavior
      in adult mice. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, the stress
      response and memory are impaired predominantly in males and only after puberty.
      To determine the neurochemical changes resulting from the reduced TGFalpha levels
      that could explain the reported behavioral outcomes, biogenic amine and amino
      acid levels were determined in the brain regions associated with stress and
      memory. Interestingly, sex-specific alterations in neurochemical levels were
      detected, including elevated noradrenaline and reduced glutamate levels in
      striatum of Wa-1 males, increased noradrenaline and reduced serotonin metabolite
      levels in hippocampus of Wa-1 females, reduced serotonin metabolite levels in
      cortex and amygdala of Wa-1 females, and reduced noradrenaline, dopamine,
      serotonin, glutamate and glycine levels in hypothalamus of Wa-1 females compared
      to their respective controls. Increased dopamine turnover in cortex and reduced
      dopamine and serotonin turnover in amygdala were observed in both male and female
      Wa-1 mice. The data indicate sex-specific alterations of specific neurochemicals
      as a result of reduced TGFalpha expression, which may underlie sex-dependent
      stress response and memory impairment in Wa-1 mice.

PMID- 16442135
TI  - Faecal corticosterone concentrations indicate that separately housed male mice
      are not more stressed than group housed males.
AB  - Mice account for over 80% of all animals used in experimentation. This study
      investigated how different housing conditions affected stress levels by measuring
      both corticosterone levels, using non-invasive faecal collection, and behaviour.
      Sixty outbred MF1 male mice were used which were separated into five different
      housing conditions at the beginning of the study, (A) individually housed, floor
      area 490 cm(2) per individual, (B) groups of three mice, floor area 163 cm(2) per
      individual, (C) groups of three mice, floor area 320 cm(2) per individual, (D)
      groups of six mice, floor area 160 cm(2) per individual, (E) groups of six mice,
      floor area 230 cm(2) with extra height per individual to allow visual contact.
      Mice in all housing conditions were provided with a basic enrichment of paper
      bedding and a plastic house. The results from this study showed that singly
      housed mice reduced their corticosterone levels over time after separation
      reaching a minimum from 14 days onwards. Groups of 6 mice housed together showed
      no difference over time. Also there was no significant difference in
      corticosterone levels between the different housing densities, with no
      differences for aggression or stereotypical behaviour suggesting that there is no
      ideal group density for this strain and sex of mouse. Providing additional
      enrichment to the cages caused a significant decrease in corticosterone levels
      for group housed mice, but individually housed mice remained unaffected by
      increasing their enrichment level. They spent significantly more time sleeping in
      the enhanced cage but without any reduction in stereotypical behaviour. For group
      housed mice, additional enrichment should be mandatory to reduce stress levels
      and therefore increase their welfare standards, while singly housed mice required
      only basic levels of enrichment and should be separated from their group for a
      minimum of 2 weeks before measurements are taken.

PMID- 16442136
TI  - Cytonuclear disequilibria in a spatially structured hybrid zone.
AB  - A hybrid zone model was developed that uses a stepping-stone model of population
      structure along with both nuclear and cytoplasmic genotypes to evaluate the
      effect that migration has on random mating organisms when no selection is
      present. Numerical simulations indicate that a number of different allele
      frequency and cytonuclear disequilibrium patterns can be found across the hybrid
      zone when it has reached equilibrium, and these results are discussed in the
      context of relative migration rates of the two sexes and the two source
      populations. The importance of numbers of subpopulations sampled, census time,
      and the persistence of pure species individuals into the hybrid zone are also
      discussed. Although this model does not consider selection or assortative mating
      in the hybrid zone, it should provide a useful baseline for evaluating joint
      cytonuclear genetic data from a structurally complex hybrid zone.

PMID- 16442137
TI  - A master equation for a spatial population model with pair interactions.
AB  - We derive a closed master equation for an individual-based population model in
      continuous space and time. The model and master equation include Brownian motion,
      reproduction via binary fission, and an interaction-dependent death rate
      moderated by a competition kernel. Using simulations we compare this individual
      based model with the simplest approximation, the spatial logistic equation. In
      the limit of strong diffusion the spatial logistic equation is a good
      approximation to the model. However, in the limit of weak diffusion the spatial
      logistic equation is inaccurate because of spontaneous clustering driven by
      reproduction. The weak-diffusion limit can be partially analyzed using an exact
      solution of the master equation applicable to a competition kernel with infinite
      range. This analysis shows that in the case of a top-hat kernel, reducing the
      diffusion can increase the total population. For a Gaussian kernel, reduced
      diffusion invariably reduces the total population. These theoretical results are
      confirmed by simulation.

PMID- 16442138
TI  - Effects of predation pressure on species packing on a resource gradient: insights
      from nonlinear dynamics.
AB  - The classical case of three competitors arranged on a resource gradient such that
      the central competitor will be excluded due to competition from the other two is
      studied from the point of view of the effects of added predators. The basic
      formulation is motivated by a desire to understand the effects of asymmetries in
      multidimensional Lotka-Volterra systems. We first study the effects of perfectly
      specialist predators and find a rich collection of possible behaviors of the
      system including (1) extinction of all predators and subsequent extinction of the
      subordinate competitor, (2) dominant competitors and their predators coexist but
      the subdominant competitor goes extinct, (3) all species except the predator of
      the subordinate competitor coexist in coordinated phase-reversed chaos, (4)
      exclusion of one or more species occurs through an expanding heteroclinic cycle,
      and (5) all species coexist in an uncoordinated chaos. We then study the effects
      of five qualitatively distinct forms of polyphagy. In one case, corresponding to
      the well-known vulnerability to predation versus competitive ability trade-off,
      it is possible to have the subordinate competitor be the only survivor in the
      system. The other three cases of polyphagy lead to distortions in the basic
      pattern seen in the previously analyzed specialist case. Studying this case of
      ecologically motivated asymmetries in the basic Lotka-Volterra formulation is a
      step in the direction of fully understanding interacting populations.

PMID- 16442139
TI  - Effects of selenocystine on lead-exposed Chinese hamster ovary (CHO) and PC-12
      cells.
AB  - Lead is a pervasive environmental toxin that affects multiple organ systems,
      including the nervous, renal, reproductive, and hematological systems. Even
      though it is probably the most studied toxic metal, some of the symptoms of lead
      toxicity still cannot be explained by known molecular mechanisms. Therefore, lead
      induced oxidative stress has recently started to gain attention. This in vitro
      study confirms the existence of oxidative stress due to lead exposure.
      Administration of lead acetate (PbA) to cultures of Chinese hamster ovary cells
      (CHO) had a concentration-dependent inhibitory effect on colony formation and
      cell proliferation. This inhibition was eliminated by 5 microM selenocystine
      (SeCys). In order to evaluate the nature of SeCys's effect, we measured
      glutathione (GSH), its oxidized form glutathione disulfide (GSSG),
      malondialdehyde (MDA), catalase, and GSH peroxidase (GPx) activities in lead
      exposed CHO cells both in the presence and absence of SeCys. Increases in MDA,
      catalase, and GPx activities were observed in cultures that received only PbA,
      but supplementation with SeCys returned these measures to pretreatment levels.
      The ratio of GSH to GSSG increased in lead-exposed cells incubated in SeCys
      enhanced media but declined in cultures treated with PbA only. In order to
      determine whether SeCys also reverses lead-induced neurotoxicity, a neuronal cell
      line, PC-12 cells, was used. Lead's inhibition on neurite formation was
      significantly eliminated by SeCys in PC-12 cells. Our results suggest that SeCys
      can confer protection against lead-induced toxicity in CHO cells and
      neurotoxicity in PC-12 cells.

PMID- 16442140
TI  - Role of V protein RNA binding in inhibition of measles virus minigenome
      replication.
AB  - Measles virus V protein represses genome replication through a poorly understood
      mechanism, which led us to investigate whether V protein might be an RNA-binding
      modulatory factor. Recombinant V protein, expressed from transfected HEp-2 cells
      or E. coli, formed protein-RNA complexes with poly-guanosine (poly-G) or poly-U
      linked to agarose beads. RNA binding was not exclusive to ribonucleotide
      homopolymers as complex formation between V protein and an RNA molecule
      equivalent to the 3' terminal 107 bases of the measles virus genome was observed
      with an electrophoretic mobility shift assay (EMSA). The interaction with poly-G
      was used to further examine the RNA binding properties of V demonstrating that
      protein-RNA complex formation was dependent upon the unique Cys-rich carboxy
      terminus, a region also required to induce maximal repression of minireplicon
      encoded reporter gene expression in transient assays. Surprisingly, two mutant
      proteins that contained Cys-to-Ala substitutions in the C-terminus were found to
      retain their ability to bind poly-G binding and repress minireplicon reporter
      gene expression indicating that neither activity was dependent on the integrity
      of all 7 C-terminal Cys residues. Additional genetic analysis revealed that amino
      acids 238-266 were necessary for efficient RNA binding and overlapped with
      residues (238-278) required for maximal repression induced by the C-terminal
      domain. In addition, a 10 amino acid deletion was identified (residues 238-247)
      that blocked RNA binding and repression indicating that these two activities were
      related.

PMID- 16442141
TI  - Functional characterization of Bombyx mori nucleopolyhedrovirus late gene
      transcription and genome replication factors in the non-permissive insect cell
      line SF-21.
AB  - We compared the abilities of late gene transcription and DNA replication
      machineries of the baculoviruses Autographa californica nucleopolyhedrovirus
      (AcMNPV) and Bombyx mori NPV (BmNPV) in SF-21 cells, an insect-derived cell line
      permissive for AcMNPV infection. It has been well established that 19 AcMNPV late
      expression factors (lefs) stimulate substantial levels of late gene promoter
      activity in SF-21 cells. Thus, we constructed a set of clones containing the
      BmNPV homologs of the AcMNPV lefs under control of the constitutive Drosophila
      heat shock 70 protein promoter and tested their ability to activate an AcMNPV
      late promoter-reporter gene cassette in SF-21 cells. We tested the potential of
      individual or predicted functional groups of BmNPV lefs to successfully replace
      the corresponding AcMNPV gene(s) in transient late gene expression assays. We
      found that most, but not all, BmNPV lefs were able to either fully or partially
      substitute for the corresponding AcMNPV homolog in the context of the remaining
      AcMNPV lefs with the exception of BmNPV p143, ie-2, and p35. BmNPV p143 was
      unable to support late gene expression or be imported into the nucleus of cells
      in the presence of the AcMNPV or the BmNPV LEF-3, a P143 nuclear shuttling
      factor. Our results suggest that host-specific factors may affect the function of
      homologous proteins.

PMID- 16442142
TI  - Application of chemometrics in river water classification.
AB  - The main aim of this work is focused on water quality classification of the Brda
      river (Poland) and evaluation of pollution data obtained by the monitoring
      measurement during the period 1994-2002. The study presents the application of
      selected chemometric techniques to the pollution monitoring dataset, namely,
      cluster analysis, principal component analysis, discriminant analysis and factor
      analysis. The obtained results allowed to determine natural clusters and groups
      of monitoring locations with similar pollution character and identify important
      discriminant variables. Chemometric analysis confirmed the classification of
      water purity of the Brda river made by the Inspection of Environmental Protection
      but the results showed more differentiation between monitored locations. This
      enables better evaluation of the water quality in a monitored region. On the
      basis of the chemometric approach, it was also found that some locations were
      under the high influence of municipal contamination, and some others under the
      influence of agriculture (discharges from fields) within the observed time
      period.

PMID- 16442143
TI  - Dissipation of DDT in a heavily contaminated soil in Mato Grosso, Brazil.
AB  - After the prohibition of organochlorine-pesticide use in Brazil for controlling
      insect vector diseases, Mato Grosso State gathered the exceeding DDT and stored
      it irregularly in an open air area that belongs to the National Health
      Foundation, causing soil contamination. This study aimed to evaluate the
      contamination level and dissipation of p,p'-DDT and p,p'-DDE in this area. For
      that, surface soil samples were collected on 19 September 2000, 15 December 2000,
      4 April 2001 and soil samples 30-40 cm; 60-70 cm and 90-100 cm deep were taken
      from five points in the studied area on 17 July 2001. The contaminants were
      determined by a small scale method which consists on extraction and clean-up
      steps combined into one step by transferring soil samples mixed with neutral
      alumina to a chromatographic column prepacked with neutral alumina and elution
      with hexane:dichloromethane (7:3 v:v). The eluate was concentrated and the
      analytes were quantified by gas chromatography with an electron-capture detector.
      p,p'-DDT at surface soil ranged from 3,800 to 7,300 mg kg(-1). 30-40 cm deep soil
      sample concentrations varied from 0.036 to 440 mg kg(-1) while 90-100 cm deep
      samples varied from 0.069 to 180 mg kg(-1). Volatilization is probably the main
      dissipation process. The p,p'-DDT is moving slowly downward in the soil profile,
      however, the levels of this contaminant are high enough to present risk to
      underground waters.

PMID- 16442144
TI  - Dioxin and dioxin-like PCB exposure of non-breastfed Dutch infants.
AB  - The exposure of humans to PCDD/Fs (polychlorinated dibenzo-p-dioxins and
      dibenzofurans) and dioxin-like PCBs (dl-PCBs, i.e. polychlorinated non-ortho and
      mono-ortho biphenyls) occurs predominantly via the intake of food. Young children
      have a relatively high intake of these substances, due to their high food
      consumption per kilogram body weight. As the exposure of non-breastfed infants to
      these compounds has not been assessed before in The Netherlands, we studied the
      dietary intake of 17 PCDD/Fs and 11 dioxin-like PCBs in 188 Dutch non-breastfed
      infants between 4 and 13 months. The food intake of the infants was assessed by a
      2-d food record. From these data PCDD/F and dioxin-like PCB intake was calculated
      using PCDD/F and dioxin-like PCB concentrations of food products sampled in
      1998/1999 in The Netherlands. The long-term PCDD/F and dioxin-like PCB exposure
      of the infants was calculated using the statistical exposure model (STEM). For
      infants of 5 months the chronic exposure to PCDD/F and dioxin-like PCB was 1.1pg
      WHO-TEQ (toxic equivalents) per kilogram body weight (bw) per day (95th
      percentile: 1.7pg WHO-TEQ/kg bwxd), which mainly originated from infant formula
      and vegetables and increased to 2.3pg WHO-TEQ/kg bwxd (95th percentile 3.7pg WHO
      TEQ/kg bwxd) for infants just over 1 year old eating the same food as their
      parents. The percentage of formula-fed infants with an exposure exceeding the TDI
      of 2pg WHO-TEQ/kg bwxd was 5% at 5 months, 49% at 9 months and 64% at 12 months.

PMID- 16442145
TI  - Characteristics of organic matter in PM2.5 in Shanghai.
AB  - Solvent extractable organic compounds (SEOC), organic carbon, elemental carbon
      and water soluble organic carbon (WSOC) in PM(2.5) samples collected in Shanghai,
      China in 2002 and 2003 were measured to determine the composition and sources of
      the organic matter in atmospheric aerosols. Distinct seasonal variations were
      detected with higher concentrations of organic matter in winter. The
      concentration of total carbon of about 20 microg m(-3) in winter was about three
      times the summer value. About 30% of the total carbon was water soluble.
      Unresolved complex mixture (UCM) and fatty acids were the most abundant
      components quantified in SEOC, similar to other Chinese cities previously
      studied. High ratio of UCM to n-alkanes (U:R) and the composition of triterpanes
      indicated that engine exhaust was a major source of the airborne organic matter.
      Emissions from coal burning had more impact in the rural areas, according to the
      U:R value and PAHs composition. Chemical mass balance (CMB) modeling shows that
      about half of the organic carbon was from engine exhaust and about 15% was from
      coal burning. No clear spatial variation in the concentration of the organic
      matter was found between urban and rural areas. Our results showed that due to
      the rapid urbanization and relocation of industrial plants from urban areas to
      rural areas in the past 20 years, air pollution in rural areas is becoming a
      serious problem in Shanghai and the Yangtze River delta.

PMID- 16442146
TI  - The occurrence of polybrominated diphenyl ethers in river and coastal biota from
      Portugal.
AB  - Throughout this work PBDEs level determination in biota was developed for the
      first time in Portugal. The data obtained was important to provide a global
      perspective of Portugal contamination by PBDEs and allows the comparison with
      studies made in other countries. Environmental levels of fourteen polybrominated
      diphenyl ethers (PBDEs) were analysed in a number of biota samples (Barbus sp.
      and Mytilus galloprovincialis) taken over a large geographic range covering five
      rivers and coastal areas of Portugal. Tetrabromodiphenyl ether (BDE 47) was found
      in almost all samples ranging from not detected (nd) to 30ngg(-1) dry weight
      (dw). BDE 47 concentration is correlated with mussels weight indicating the
      bioaccumulation of this compound. Pentabromodiphenyl ethers (BDE 99 and BDE 100)
      were detected in several samples, but in lower concentrations.

PMID- 16442147
TI  - Accumulation and elimination of aqueous and dietary silver in Daphnia magna.
AB  - The dissolved uptake, dietary assimilation, and efflux of Ag in a freshwater
      cladoceran, Daphnia magna, were measured under different laboratory conditions.
      The dissolved uptake rate of Ag was proportional to the ambient Ag concentration,
      but the accumulation was highly variable due to the sorption of Ag onto the
      daphnid bodies. The ambient Na(+) but not the ambient K(+) concentration
      significantly decreased the dissolved uptake of Ag, suggesting a competitive
      uptake of Ag(+) with Na(+). The dietary assimilation efficiencies (AEs) of Ag are
      dependent on the concentration of the algal food available to D. magna. The AE
      was as low as 2% when the food concentration reached the saturation levels. In
      contrast, the Ag concentrations in the algae did not significantly affect the Ag
      AE in D. magna. The efflux rate constant of diet-incorporated Ag was twice that
      through dissolved uptake. The elimination of Ag was further separated into
      different compartments (excretion, egestion, molting, and reproduction) in the
      juveniles and adults after accumulation from dissolved and dietary sources.
      Regeneration into the dissolved phase was the predominant pathway by which the
      incorporated Ag was lost from D. magna, regardless of the exposure pathway. In
      contrast to the essential metals or Hg, there was minimal maternal transfer of Ag
      from the mothers to the offspring. By employing the biokinetic model, we further
      showed that water is a dominant pathway for Ag accumulation in D. magna. Trophic
      transfer is less significant primarily because of the low Ag AE when the food
      concentration reached the saturation levels.

PMID- 16442148
TI  - Distribution of hexabromocyclododecane in Detroit River suspended sediments.
AB  - The distribution of hexabromocyclododecane (HBCD) isomers (alpha, beta and gamma)
      was determined in Detroit River suspended sediments using liquid chromatography
      tandem mass spectrometry (LC/MS/MS). Individual isomers of HBCD were measured at
      concentrations ranging from <0.025 to 1.9 ng/g (dry wt.) for the alpha-isomer,
      <0.025 to 0.28 ng/g for the beta-isomer, and <0.025 to 2.3 ng/g for the gamma
      isomer. Concentrations of total HBCD ranged from <0.075 to 3.7 ng/g. Roughly two
      thirds of HBCD profiles in suspended sediments were dominated by the gamma
      isomer, and were similar to profiles of commercial technical mixtures. Profiles
      in the remaining samples were dominated by the alpha-isomer. The beta-isomer was
      consistently detected at substantially lower levels than the other isomers; this
      isomer is a minor constituent in the commercial technical mixtures. Seasonal
      sampling showed significant shifts in the relative ratios of the HBCD isomers.
      The spatial distribution of HBCD in the Detroit River was similar to other
      persistent organic pollutants (e.g., PCBs), and showed a strong association with
      urban/industrial activities in the watershed. However, the highest HBCD
      concentrations (2.6-3.7 ng/g) were associated with areas of contemporary
      industrial activity, and were much lower than maximum concentrations of PCBs (2.2
      microg/g) found in areas of the Detroit River associated with historical
      industrial activity.

PMID- 16442150
TI  - Anaerobic degradation of brominated flame retardants in sewage sludge.
AB  - Tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and
      decabromodiphenyl ether (DecaBDE) are high production volume chemicals used as
      flame retardants in plastics for products such as electronic equipment,
      insulation panels, and textiles. The environmental safety of brominated flame
      retardants, especially their persistence, bioaccumulation, and toxicity is a
      controversial topic. Here, we studied and compared the degradation of TBBPA,
      HBCD, and DecaBDE under anaerobic conditions in digested sewage sludge. The half
      lives of TBBPA and a technical HBCD mixture were 0.59 and 0.66 d, respectively.
      The fact that (+/-)-alpha-HBCD exhibited an almost doubled half-life compared to
      (+/-)-beta-HBCD and (+/-)-gamma-HBCD is an important finding with respect to the
      discussion on the persistence of individual HBCD stereoisomers and the recent
      reports on strong relative enrichment of alpha-HBCD in biota. We found no
      statistically significant enantioselective degradation of alpha-, beta-, or gamma
      HBCD. Half-lives of TBBPA and a technical HBCD mixture were not dependent on the
      presence of additional nutrients or primers. Concentrations of TBBPA and a
      technical HBCD mixture decreased also in sterile control samples, however, at a
      rate that was more than a factor of 50 smaller than in incubations under non
      sterile conditions. Compared to TBBPA and a technical HBCD mixture, DecaBDE
      exhibited a much longer half-life of 7 x 10(2)d in the same system. Pseudo-first
      order degradation rate constants decreased according to the following sequence:
      TBBPA congruent with(+/-)-gamma-HBCD congruent with(+/-)-beta-HBCD>(+/-)-alpha
      HBCD>>DecaBDE. Preliminary investigations suggest that degradation of TBBPA,
      HBCD, and DecaBDE occurs in full-scale anaerobic digesters, as well.

PMID- 16442149
TI  - Analysis of the health risk of exposure to breast milk mercury in infants in
      Taiwan.
AB  - The aim of this study was to assess the total concentration and health risk to
      infants of breast milk mercury in urban mothers and mothers married to fishermen
      in relation to fish intake in Taiwan. A total of sixty-eight healthy mothers were
      recruited for the study. The breast milk mercury geometric mean concentration was
      2.02 microgl(-1) (n=56, range: 0.24-9.45 microgl(-1)) for the city group and 2.04
      microgl(-1) (n=12, range: 0.26-8.62 microgl(-1)) for the fishermen's group. Of
      the three sources of mercury exposure (i.e., ingestion (breast milk), inhalation
      (ambient air), and dermal exposure (shower)), breast-feeding was found to be the
      largest (96.3-99.6% of the total). From a Monte Carlo simulation, in which methyl
      mercury accounted for about 50% of total mercury, the hazard quotient (exposure
      estimate/oral minimal risk level or target organ toxicity dose) exceeded 1.0 for
      12.9% of urban babies and 18.8% of fishermen's babies (chronic oral minimal risk
      level and target organ toxicity dose: 3 x 10(-4)mgkg(-1)d(-1)). The calculated
      mercury exposure was 3.02 x 10(-1) microgkg(-1)d(-1) for a 3.49 kg urban baby boy
      and 3.06 x 10(-1) microgkg(-1)d(-1) for a 3.44 kg urban baby girl. These results
      suggest the life style of mothers (eating raw fish and shellfish such as used in
      "Sashimi" and "Sushi," and vitamin supplementation) may influence the mercury
      concentration in breast milk.

PMID- 16442151
TI  - Geostatistical assessment of Pb in soil around Paris, France.
AB  - This paper presents a survey on soil Pb contamination around Paris (France) using
      the French soil monitoring network. The first aim of this study is to estimate
      the total amount of anthropogenic Pb inputs in soils and to distinguish Pb due to
      diffuse pollution from geochemical background Pb. Secondly, this study tries to
      find the main controlling factors of the spatial distribution of anthropogenic
      Pb. We used the technique of relative topsoil enhancement to evaluate the
      anthropogenic stock of Pb and we performed lognormal kriging to map Pb regional
      distribution. The results show a strong gradient of anthropogenic stock of Pb
      around the urban Paris area. We estimate a total amount of anthropogenic stock of
      Pb close to 143,000 metric tons, which corresponds to an average accumulation of
      5.9 t km(-2). Our study suggests that a grid-based survey can help to quantify
      diffuse Pb contamination by using robust techniques of calculation and that it
      might also be used to validate predictions of deposition models.

PMID- 16442152
TI  - Characterizing natural organic material from the Occoquan Watershed (Northern
      Virginia, US) using fluorescence spectroscopy and PARAFAC.
AB  - Surface water samples from the Occoquan Watershed (Virginia, US) were collected
      during summer baseflow conditions and characterized by excitation-emission matrix
      (EEM) fluorescence spectroscopy and parallel factor analysis (PARAFAC). Based on
      55 samples, PARAFAC identified three individual fluorophore moieties, which were
      attributed to humic-like, fulvic-like, and protein-like materials. The
      categorization of these seemingly universal fluorophore moieties in aqueous
      systems was consistent with expected analyte concentrations that were
      independently measured by traditional wet chemistry techniques. The relative
      distribution of the three fluorophore fractions varied among the different land
      use catchments, especially in locations of known anthropogenic activity.
      Distinctive relationships between the fulvic-like and protein-like materials were
      observed for catchments known to be influenced by anthropogenic activity and
      those believed to reflect more natural environments, suggesting that this
      technique could be used to monitor human impact on aquatic systems. Finally,
      PARAFAC can be used to provide estimates (+/-30%) of select analyte
      concentrations in surface water. The results of this study support the use of EEM
      and PARAFAC analyses by watershed managers and other personnel interested in
      understanding organic matter behavior in aquatic systems.

PMID- 16442153
TI  - A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy
      in patients with advanced ovarian cancer responsive to primary surgery and
      paclitaxel/platinum containing chemotherapy: a National Cancer Institute of
      Canada Clinical Trials Group Study.
AB  - OBJECTIVE: BAY 12-9566 (tanomastat) is a biphenyl matrix metalloprotease
      inhibitor (MMPI) with antiangiogenic and antimetastatic properties in vivo. The
      objective of the study was to determine whether the addition of BAY 12-9566 after
      optimal response to chemotherapy could improve time to progression (TTP).
      PATIENTS AND METHODS: Patients enrolled in the study had received 6-9 cycles of
      platinum/paclitaxel containing chemotherapy for stage III or IV ovarian
      carcinoma, with a response of no evidence of disease, or complete or partial
      response with residual disease < 2 cm. Patients were then randomized to BAY 12
      9566 800 mg p.o. b.i.d. or placebo. The primary endpoint was progression-free
      survival (PFS); secondary endpoints were quality of life, toxicity, changes in CA
      125 levels, response, and overall survival (OS). The total planned sample size
      was 730. RESULTS: The study was closed after 243 patients had been randomized
      because of Bayer's decision to close all ongoing trials due to negative results
      from other phase III trials in pancreatic and small cell lung cancer. The final
      analysis was performed in August 2000 after the requisite number of events for
      the first planned interim analysis had occurred; 54% of patients had progressed
      and 18% had died. PATIENT CHARACTERISTICS: performance status was ECOG 0/1/2 in
      65/33/2%; median age 57 years; 79% of patients were FIGO stage III; 41% were
      optimally debulked; 76% had serous histology, and 67% had > or = grade 3
      histology. Toxicity was generally grade 1 or 2 in severity, with the most common
      (BAY 12-9566 vs. placebo) being nausea (26% vs. 13%), fatigue (24% vs. 12%),
      diarrhea (14% vs. 10%), rash (12% vs. 7%), grade 3/4 thrombocytopenia (3% vs.
      1%), and grade 3/4 anemia (5% vs. 1%). Median time to progression (TTP) was 10.4
      months (8.5-11.5) for BAY 12-9566 and 9.2 months (7.2-13.9) for placebo (P =
      0.67). Median overall survival (OS) was 13.9 months (12.9-infinity) for BAY 12
      9566 and 11.9 months (10.5-16.5) for placebo (P = 0.53). CONCLUSION: We conclude
      that BAY 12-9566 was generally well tolerated and at the time of the final
      analysis, there was no evidence of an impact of BAY 12-9566 on PFS or OS.

PMID- 16442154
TI  - Test-retest reliability of self-reported mammography in women veterans.
AB  - BACKGROUND: Mammography self-report is used to monitor screening and evaluate
      intervention trends; however, few studies have examined reliability. METHODS:
      Reliability of self-reported lifetime number of mammograms, most recent mammogram
      date, and predictors of reliability were assessed using data from Project
      H.O.M.E. The study population was 2,494 women 52 years and over, listed in the
      U.S. National Registry of Women Veterans, with no history of breast cancer, who
      completed both baseline (2000-2002) and year 1 (2002-2003) surveys. RESULTS:
      Reliability of lifetime number of mammograms was 60.9% for exact consistency and
      79.9% for consistency within one mammogram. Thirty-five percent was exactly
      consistent in reporting mammogram date; 55.6% was consistent within 3 months.
      Completing both surveys by mail and reporting fewer lifetime mammograms at
      baseline were positively associated with consistency of reporting lifetime
      number. White race/ethnicity, having a Bachelor's degree, reporting a health care
      provider's recommendation for a mammogram, having a screening mammogram,
      completing both surveys by mail, and being in the maintenance or action stages of
      change were associated with consistency in reporting date. CONCLUSIONS:
      Reliability varies with the measure of self-reported mammography. Likewise,
      predictors show different patterns of association with different definitions. Our
      findings call attention to the need for explicit definitions and measures of
      mammography use.

PMID- 16442155
TI  - Effects of oxygen tension and supplements to the culture medium on activation and
      development of bovine follicles in vitro.
AB  - Our laboratory developed a method for culturing small pieces of bovine and baboon
      ovarian cortex, rich in primordial follicles, that supports the initiation of
      follicle growth and development to the primary stage. However, only a few
      follicles progressed to the secondary stage. The purpose of the current
      experiments was to determine if changes in culture conditions, specifically
      oxygen concentration and supplements to the culture medium, would facilitate the
      primary to secondary follicle transition. In Experiment 1, ovarian cortical
      pieces from late-gestation bovine fetuses were cultured with 2, 5, 20, or 60%
      oxygen in Waymouth's medium plus ITS+ (insulin, transferrin, selenium plus
      linoleic acid and BSA). Although the three lower concentrations of oxygen were
      generally equivalent in promoting follicle activation and growth, the highest
      concentration (60%) had deleterious effects on follicle survival after 7 days in
      culture, reducing the number of healthy follicles to about 35% of the number
      observed with 20% oxygen (P<0.05). In Experiment 2, bovine ovarian cortical
      pieces were cultured in the standard gas mixture (5% CO(2) in air) with graded
      doses of fetal bovine serum (FBS, 2.5, 5, or 10%) in the presence or absence of
      0.5 or 1x ITS+. All concentrations of FBS alone were much less effective at
      maintaining follicular health and supporting the initiation and progression of
      follicular growth than was ITS+. However, 5 and 10% FBS alone increased the
      percentage of healthy primordial and primary follicles by about twofold (P<0.05)
      in the absence of ITS+ and in the presence of 0.5x ITS+, they enhanced the
      primary to secondary follicle transition by 10- and 9-fold, respectively. Thus,
      of the culture conditions evaluated, 20% oxygen and medium containing 0.5x ITS+
      plus 5% or 10% FBS were the most effective for promoting follicular health and
      development.

PMID- 16442156
TI  - Tensile bond strength of dual curing resin-based cements to commercially pure
      titanium.
AB  - OBJECTIVES: The aim of this study was to evaluate the tensile bond strength of
      dual curing luting resin cements to commercially pure titanium at 10 min and 24h
      after removal of the oxide layer. METHODS: One hundred and twenty titanium discs
      were obtained by casting and polishing with silicon carbide papers. The titanium
      discs were sandblasted with 50 microm aluminum oxide, ultrasonic cleaned and
      bonded in pairs with the resin-based cements Panavia F and Rely X ARC at 10 min
      and 24h after the sandblasting. The tensile test was performed with a crosshead
      speed of 0.5mm/min in an Instron Universal testing machine. RESULTS: The Rely X
      ARC reached the highest tensile strength value at 24h after sandblasting (18.27
      MPa), but there was no statistically significant difference between the two dual
      curing resin cements for both times tested. All specimens showed a mixture of
      cohesive fracture in the resin cement and adhesive failure. However, the
      predominant failure mode for Panavia F was cohesive in resin cement, and the Rely
      X ARC exhibited a greater proportion of specimens with adhesive failure between
      the alloy and resin luting cement at 10 min and 24h. SIGNIFICANCE: Both cements
      had, statistically, the same tensile bond strength. But in the fracture mode
      analysis, the adhesive predominant fracture mode of Rely X ARC cement indicates a
      premature clinical adhesive failure. On the other hand, the cohesive predominant
      fracture mode of Panavia F indicates a longer clinical adhesive bond with
      titanium.

PMID- 16442157
TI  - Treatment of articular cartilage defects in horses with polymer-based cartilage
      tissue engineering grafts.
AB  - The objective of our study was to evaluate the integration of autologous
      cartilage tissue engineering transplants based on resorbable
      polyglactin/polydioxanone scaffolds into full-thickness cartilage defects of
      horses. Cartilage biopsies were taken from the non-load-bearing area of the
      lateral talus of the left tibiotarsal joint of eight healthy Haflinger horses.
      Tissue engineering cartilage transplants were generated by three-dimensional
      arrangement of autologous chondrocytes in biocompatible and resorbable polymer
      scaffolds. Full-thickness cartilage defects of 8 mm in diameter were created in
      the tubular bone condyle of the fetlock joint and cartilage grafts were fixed
      using an anchor system, while defects without grafting served as controls. After
      6 and 12 months the repair tissue was evaluated histologically and showed
      formation of a cartilaginous tissue and good integration into the surrounding
      host tissue with firm bonding of the graft to the adjacent cartilage and the
      underlying subchondral bone. Biochemical analysis demonstrated that the content
      of glycosaminoglycans and hydroxyproline is comparable in repair tissue derived
      from treated and control defects. The use of three-dimensional autologous
      cartilage transplants based on resorbable polymer scaffolds ensures secure
      fixation, good integration of the graft into cartilage lesions, and is therefore
      suggested as a promising therapeutic option for the treatment of cartilage
      defects.

PMID- 16442158
TI  - Differences in integrin-dependent phagocytosis among three hemocyte
      subpopulations of the Pacific oyster "Crassostrea gigas".
AB  - Integrins play a key role in immunoresponses such as attachment, spreading, and
      phagocytosis in invertebrate hemocytes. This study was designed to identify
      integrin expression patterns at the hemocyte subpopulation level, and correlate
      the expression levels with phagocytic ability. First, we cloned a beta integrin
      from Crassostreagigas hemocytes and used real-time RT-PCR to analyze the
      quantitative expression level of its encoding mRNA. The expression level in
      hyalinocytes was significantly higher than that in granulocytes and
      agranulocytes. Subsequently, we investigated the phagocytic ability of each
      subpopulation using anti-alpha(5)beta(1) integrin antibody, and found that
      phagocytosis of hyalinocytes was inhibited by neutralization with the antibody
      but enhanced against the antibody-conjugated microspheres. In contrast,
      phagocytic abilities of granulocytes and agranulocytes showed high and zero
      levels, respectively, regardless of the antibody. These results suggest that
      phagocytosis of hyalinocytes is regulated by an integrin-dependent mechanism and
      that of granulocytes is elicited by other functional receptors.

PMID- 16442159
TI  - Cloning and characterization of a LPS-regulatory gene having an LPS binding
      domain in kuruma prawn Marsupenaeus japonicus.
AB  - LPS is known as an effective stimulator of the immune system in various animals,
      including mammals and horseshoe crabs (HSC). Both of these animal groups have
      suppressive regulatory proteins for the LPS response, e.g. the
      bactericidal/permeability increasing protein in mammals and anti-LPS factor (ALF)
      in HSC. Prawns are a valuable aquaculture species, but the regulatory molecules
      and/or mechanisms that respond to LPS are largely unknown. To investigate the
      molecular mechanism of the LPS response in kuruma prawns, we cloned a cDNA having
      a LPS binding domain. A full-length cDNA gene, denoted as M-ALF (Marsupenaeus
      japonicus ALF-like peptide) was cloned that consisted of 746bp and encoded 123
      amino-acid residues. The 3' non-translated region of this gene had the pentamer
      of ATTTA repeated four times; this is known as sequences for messenger RNA
      stabilization. Deduced amino-acid sequences showed a 42% homology with Japanese
      HSC-ALF. In particular, both have clusters of basic and hydrophobic amino acids,
      indicating that the region is probably binding to lipid A. The mRNA expression
      was determined for hemocytes, lymphoid organs, hearts, intestines and gills by RT
      PCR. The mRNA expression was augmented 1.5-3h after LPS administration in
      lymphoid organs, but then decreased to normal level at 6h. Synthetic peptides
      containing Cys30 to Cys51 had LPS neutralizing activity to the Limulus reaction
      and NO production in RAW264.7 cells. These data suggest that in kuruma prawns, M
      ALF acts as a LPS regulator during the acute phase response after invasion of
      pathogens.

PMID- 16442160
TI  - Neuroimaging in manganism.
AB  - Neuroimaging such as magnetic resonance imaging (MRI), positron emission
      tomography (PET), and single-photon emission computed tomography (SPECT) have
      been used in the last decade for investigating the neurotoxicolgy of manganese
      (Mn). Increased signal intensities on a T1-weighted image may reflect increased
      Mn deposits (e.g., due to exposure to Mn) but not necessarily manganism. In a
      biologically based dose-response model, our recent results strongly suggest that
      signal intensities in T1-weighted MRI reflect a target site dose. However, the
      threshold of signal intensity associated with clinical symptoms of manganism
      remains to be solved. Functional neuroimaging such as PET or SPECT examines the
      integrity of the nigrostriatal dopaminergic system, and thus is very important
      for the differential diagnosis of manganism. However, neuroimaging research
      should also aim at developing specific and sensitive parameters for manganism in
      Mn-exposed individuals.

PMID- 16442161
TI  - Evaluation of developmental neurotoxicity of organotins via drinking water in
      rats: monomethyltin.
AB  - Organotins such as monomethyltin (MMT) are widely used as heat stabilizers in PVC
      and CPVC piping, which results in their presence in drinking water supplies.
      Concern for neurotoxicity produced by organotin exposure during development has
      been raised by published findings of a deficit on a runway learning task in rat
      pups perinatally exposed to MMT (Noland EA, Taylor DH, Bull RJ. Monomethyl and
      trimethyltin compounds induce learning deficiencies in young rats. Neurobehav
      Toxicol Teratol 1982;4:539-44). The objective of these studies was to replicate
      the earlier publication and further define the dose-response characteristics of
      MMT following perinatal exposure. In Experiment 1, female Sprague-Dawley rats
      were exposed via drinking water to MMT (0, 10, 50, 245 ppm) before mating and
      throughout gestation and lactation (until weaning at postnatal day [PND] 21).
      Behavioral assessments of the offspring included: a runway test (PND 11) in which
      the rat pups learned to negotiate a runway for dry suckling reward; motor
      activity habituation (PNDs 13, 17, and 21); learning in the Morris water maze (as
      adults). Other endpoints in the offspring included measures of apoptosis (DNA
      fragmentation) at PND 22 and as adults, as well as brain weights and
      neuropathological evaluation at PND 2, 12, 22, and as adults. There were no
      effects on any measure of growth, development, cognitive function, or apoptosis
      following MMT exposure. There was a trend towards decreased brain weight in the
      high dose group. In addition, there was vacuolation of the neuropil in a focal
      area of the cerebral cortex of the adult offspring in all MMT dose groups (1-3
      rats per treatment group). In Experiment 2, pregnant rats were exposed from
      gestational day 6 until weaning to 500 ppm MMT in drinking water. The offspring
      behavioral assessments again included the runway task (PND 11), motor activity
      habituation (PND 17), and Morris water maze (as adults). In this second study,
      MMT-exposed females consumed significantly less water than the controls
      throughout both gestation and lactation, although neither dam nor pup weights
      were affected. As in Experiment 1, MMT-exposure did not alter pup runway
      performance, motor activity, or cognitive function. These results indicate that
      perinatal exposure to MMT, even at concentrations which decrease fluid intake,
      does not result in significant neurobehavioral or cognitive deficits. While mild
      neuropathological lesions were observed in the adult offspring, the biological
      significance of this restricted finding is unclear.

PMID- 16442162
TI  - An unusually late presentation of neuroschistosomiasis.
AB  - Schistosomiasis is one of the most widespread parasitic infections in man.
      Neuroschistosomiasis, referring to schistosomal involvement of the central
      nervous system, is an uncommon but well recognised complication of schistosomal
      infection. The duration between time of infection and onset of neurological
      symptoms typically varies between weeks to months. We describe a case of
      transverse myelitis secondary to neuroschistosomiasis, presenting more than three
      years after the time of initial schistosomal infection, diagnosed and treated in
      the district general hospital setting.

PMID- 16442163
TI  - Kikuchi Fujimoto disease secondary to Entamoeba histolytica: case report.
AB  - Kikuchi Fujimoto disease (KFD) is a rare histiocytic necrotizing lymphadenitis
      which has a benign self-limiting clinical course. Its origin is unknown, but an
      abnormal autoimmune reaction has been suggested and infection is often considered
      to be an inciting agent. A 50-year-old man presented with fever, malaise, fatigue
      and sweat of 7 days duration, and diarrhea for 2 days. Physical examination
      revealed five mobile and painless cervical adenopathies. Entamoeba histolytica
      trophozoites and cysts were detected by microscopy of feces. Parenteral
      ornidazole treatment was commenced. Thorax computerized tomography showed lymph
      node sizes congruent with infection in the mediastinum, right hilus and right
      axillary region. Axillary lymph node biopsy and immunohistochemical analyses were
      then performed, and the results were consistent with histiocytic necrotizing
      lymphadenitis. From day 4 of antibiotic treatment the patient's body temperature
      decreased and reached a normal level on day 10. After discharge the patient
      returned for follow-up twice and was asymptomatic; his lymph nodes were either
      unpalpable or were decreased in size. We could not find any previous study or
      case report about a probable role for E. histolytica. Amebiasis can be a
      triggering factor in KFD or alternatively it is possible that its occurrence is
      coincidental.

PMID- 16442164
TI  - Cardiolipin metabolism and Barth Syndrome.
AB  - Many advances have occurred in the field of Barth Syndrome biology in the 26
      years since it was first described as an X-linked cardiomyopathy. Barth Syndrome
      is the first human disease recognized in which the primary causative factor is an
      alteration in cardiolipin remodeling. Cardiolipin is required for the optimal
      function of many proteins within the mitochondria, particularly in the
      respiratory chain and is involved in the mitochondrial-mediated apoptotic
      process. The appropriate content of cardiolipin appears to be critical for these
      functions. Cardiolipin is synthesized de novo in mitochondria and is rapidly
      remodeled to produce CL enriched in linoleic acid. The Barth Syndrome gene TAZ
      has been identified and expression of the gene yields proteins known as
      tafazzins. Mutations in TAZ result in a decrease in tetra-linoleoyl species of
      cardiolipin and an accumulation of monolysocardiolipin within cells from Barth
      Syndrome patients. Although the protein product of the TAZ gene shows sequence
      homology to the glycerolipid acyltransferase family of enzymes, its precise
      biochemical function remains to be elucidated. In this review we highlight some
      of the recent literature on cardiolipin metabolism and Barth Syndrome.

PMID- 16442165
TI  - Development of a fluorescence assay for the detection of L-ficolin-MASP in serum
      or purified samples.
AB  - A fluorescence assay for the detection of L-ficolin-MASP in human serum or
      purified sample was developed by measuring the cleavage of fluorescent amide
      substrate by L-ficolin associated MASPs bound to the lipoteichoic acid (LTA). LTA
      (Staphylococcus aureus DSM 20233) was coated on NuncMaxisorp microtiter plates
      and serum or purified sample incubated overnight at 4 degrees C to allow the L
      ficolin-MASP to bind LTA. Assay conditions for binding and complete cleavage of
      fluorescent amide substrate were standardized. The optimum temperature,
      incubation time and molarity of NaCl for LTA-ficolin binding were found to be 4
      degrees C for 6 h at 1 M NaCl concentration. The optimum incubation time and pH
      for complete cleavage of fluorescent amide substrate by LTA bound L-ficolin
      associated MASP were found to be 2 h at pH 8.5. LTA-ficolin binding was found to
      be highly specific and was inhibited completely by LTA but not with mannose. A
      calibration curve was prepared by using the purified ficolin-MASP complex (1 to
      12 mug/ml) and could be used to find concentration of ficolin-MASP complex in
      normal human serum.

PMID- 16442166
TI  - The interactive functioning of anxiety and depression in agonistic encounters and
      reconciliation.
AB  - This paper explores the well-known overlap of anxiety and depressive symptoms in
      mood and anxiety disorders. We suggest that the regulation of both negative and
      positive affects has served important adaptive functions (especially for coping
      with threats, losses, failures and defeats), and that in some contexts both
      affect systems require regulation at the same time (e.g. increased anxiety
      coupled with low positive affect). Here we will focus on how low positive and
      high negative affect in the individual experiencing losses and defeats regulates
      their competitive and acquisitive behaviors and in some cases may prevent, de
      escalate, and possibly terminate on-going agonistic (hierarchical) encounters.
      When high negative affect (anxiety) and low positive affect (depression) fail to
      fulfill their adaptive roles, they tend to persist and often intensify. This may
      lead each affect control system to stimulate specific types of anxiety and
      depressive disorders, exhibiting features reminiscent of the original adaptive
      function of the behavior. Furthermore, as these different systems tend to operate
      in a synchronous fashion, the psychiatric syndromes they generate are often
      comorbid.

PMID- 16442167
TI  - Voice analysis in pediatric cochlear implant recipients.

PMID- 16442168
TI  - Identification of Plasmodium falciparum var1CSA and var2CSA domains that bind IgM
      natural antibodies.
AB  - Malaria in pregnancy is responsible for maternal anaemia, low-birth-weight babies
      and infant deaths. Plasmodium falciparum infected erythrocytes are thought to
      cause placental pathology by adhering to host receptors such as chondroitin
      sulphate A (CSA). CSA binding infected erythrocytes also bind IgM natural
      antibodies from normal human serum, a process that may facilitate placental
      adhesion or promote immune evasion. The parasite ligands that mediate placental
      adhesion are thought to be members of the variant erythrocyte surface antigen
      family P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var
      genes. Two var gene sub-families, var1CSA and var2CSA, have been identified as
      parasite CSA binding ligands and are leading candidates for a vaccine to prevent
      pregnancy-associated malaria. We investigated whether these two var gene
      subfamilies implicated in CSA binding are also the molecules responsible for IgM
      natural antibody binding. By heterologous expression of domains in COS-7 cells,
      we found that both var1CSA and var2CSA PfEMP1 variants bound IgM, and in both
      cases the binding region was a DBL epsilon domain occurring proximal to the
      membrane. None of the domains from a control non-IgM-binding parasite (R29) bound
      IgM when expressed in COS-7 cells. These results show that PfEMP1 is a parasite
      ligand for non-immune IgM and are the first demonstration of a specific adhesive
      function for PfEMP1 epsilon type domains.

PMID- 16442169
TI  - The Leishmania major maxicircle divergent region is variable in different
      isolates and cell types.
AB  - The maxicircle divergent region (DR) was partially sequenced in several isolates
      of Leishmania major. The sequence contains various repeated elements: two types
      of long GC-rich repeats alternating with clusters of short AT-rich repeats. The
      arrangement of repeats appears to be similar in the studied Leishmania species
      and their relative Leptomonas seymouri. Furthermore, a conserved sequence
      containing putative promoters within a palindrome was revealed in the DRs of
      these species. Unexpectedly, the DR sequence proved to be dissimilar in
      promastigotes and amastigotes of the same isolate perhaps through selection of
      parasites with particular maxicircle variants in the course of the promastigote
      amastigote differentiation. Different number of repeats and numerous single
      nucleotide polymorphisms are observed in the compared sequences. We have also
      investigated the DR structure in 21 L. major isolates by PCR and demonstrated its
      great variability. We suppose, however, that different variants of the DR
      structure are generated by combination of several highly conserved domains.

PMID- 16442170
TI  - Hypothalamic-pituitary-adrenocortical responses to psychological stress and risk
      for smoking relapse.
AB  - Stress is a commonly reported precipitant of relapse to substance use. There is a
      growing recognition of the need to understand psychobiological alterations in the
      stress response among chronic drug users, and to determine how they may
      precipitate relapse. This paper focuses on the hypothalamic-pituitary
      adrenocortical (HPA) response to stress among dependent smokers. Nicotine acutely
      activates the HPA axis, and increased HPA activity has been linked to attenuated
      CNS nicotinic receptor sensitivity. We will review a series of studies
      demonstrating that steep decline in cortisol concentrations during early
      abstinence and hyporesponsiveness to stress predict shorter time to relapse. Our
      studies show that hormonal associations with smoking relapse tend to be more
      consistent in men, while intensity of withdrawal symptoms tend to be consistent
      predictors of smoking relapse in women. We propose that perturbed HPA activity
      during early smoking abstinence exacerbate withdrawal symptoms and may contribute
      to the rapid relapse observed in the majority of smokers. Our results also
      reinforce the need for gender-specific investigation of mechanistic and
      interventional strategies to combat nicotine addiction.

PMID- 16442171
TI  - The relationship between fine and gross motor ability, self-perceptions and self
      worth in children and adolescents.
AB  - The present study examined the impact of fine and gross motor ability on self
      perceptions of male and female children and adolescents. Participants were
      compared across age group, sex, and level of motor ability. When
      intercorrelations between self-perceptions were taken into account, the level of
      movement ability was found to impact upon perceived athletic competence and
      scholastic competence. When movement was considered in terms of fine and gross
      motor ability, it was found that those with higher perceived scholastic
      competence were in the younger group and had better fine motor skills.
      Furthermore, those with greater perceived athletic competence were also in the
      younger group, were predominantly male and had better gross motor skills. The
      types of self-perceptions that influenced self-worth were dependent on the level
      of motor ability of the participants and varied according to their sex. The
      implications of these findings are discussed with reference to the necessity to
      assess specific types of motor deficit when tailoring intervention strategies for
      children with motor disorders, particularly within the academic setting.

PMID- 16442172
TI  - The relationship between measures of executive function, motor performance and
      externalising behaviour in 5- and 6-year-old children.
AB  - In his cognitive-energetic model of information processing Sergeant [Sergeant, J.
      (2000). The cognitive-energetic model: An empirical approach to ADHD.
      Neuroscience and Biobehavioral Reviews, 24, 7-12] links executive function (EF)
      to motor behaviour. This link has been supported by evidence from a number of
      sources including studies of attention deficit hyperactivity disorder (ADHD) and
      developmental coordination disorder (DCD). Little is known developmentally about
      this association. Given the rapid change in both motor proficiency and EF that
      takes place in the pre-school years, this appears an important time to look for
      the emergence of the link between these factors. In this study we tested 5- and 6
      year-old children on motor tasks from the movement assessment battery for
      children and on measures of response inhibition (Stroop and stop-signal task) and
      examined the relationship between scores on these measures. Additionally, in
      order to relate this behaviour to everyday function, the Rowe behavioural rating
      inventory (RBRI), a teachers' behavioural rating of externalising behaviour, was
      also gathered and this related to EF and motor performance. It was found that
      motor performance correlated significantly with RBRI scores (better motor
      performance with lower externalising behaviour) and with Stroop performance. The
      relationship between motor performance and stop-signal task performance was in
      the expected direction but failed to reach significance and there was no clear
      association between performance on the stop-signal task and either Stroop or RBRI
      scores. The results are discussed in relation to different aspects of response
      inhibition (inhibition of a pre-potent response, interference control) and how
      these might relate to motor control.

PMID- 16442173
TI  - ADHD and DCD: a relationship in need of research.
AB  - Although the connection between attention deficit hyperactivity disorder (ADHD)
      and developmental coordination disorder (DCD) has been recognized for several
      decades, little research has examined the relationship between these two
      disorders. This paper draws attention to the contribution the cognitive-energetic
      model (CEM) can make in determining the specific nature of these two disorders.
      An information processing approach such as the CEM is a useful model to identify
      specific and overlapping mechanisms that are disrupted in these two disorders.
      This paper describes the CEM and reviews the research so-far in relation to the
      model. The CEM has several advantages over other models: First, it predicts which
      task variables will be independent or may interact, thus enabling the
      investigator to determine the success/failure of the task manipulation(s) and
      identify spurious findings. Second, the CEM links energetic factors to task
      variables and predicts both additive and interactive effects. Third, the CEM
      enables executive processes such as selective attention, working memory and
      inhibition to be related to both energetic and lower level processes. Fourth, by
      employing the CEM in clinical research, taxonomy of deficits can be derived
      enabling further insight into the nature of the disorders and their specific
      neuropsychological dysfunction. Suggestions are made for future research into the
      neuropsychological deficits associated with ADHD and DCD.

PMID- 16442174
TI  - Developmental trends in speed accuracy trade-off in 6-10-year-old children
      performing rapid reciprocal and discrete aiming movements.
AB  - Cyclic tasks are performed better than discrete tasks in adults but it is unknown
      whether this advantage is present in children as well. Three age groups of
      participants (6, 8, and 10 years old) executed cyclic and discrete aiming
      movements to two differently sized target using a Fitts task to examine the
      developmental effects on speed/accuracy trade-off. Children showed the same
      advantage of cyclic over discrete movements as previously demonstrated for adults
      but at a slower speed. The slope of the speed accuracy trade-off was similar in
      the three age groups in the cyclic as compared to the discrete control mode,
      suggesting that children learn both tasks equally well in this age range. The
      index of performance (IP) increased with age but not differently for the two
      control modes. Children showed clear differences between the kinematics of
      discrete and cyclic movements and these differences were similar to those seen in
      adults. Cyclic movements were faster, had higher IP, showed fewer changes in
      velocity and were more ballistic. Thus movement execution was different between
      the two tasks, consistent with the hypothesis that cyclic tasks make use of
      neural oscillators. The slower movement speed in young children is consistent
      with their limited ability to use open loop control.

PMID- 16442175
TI  - Approaches to sensory-motor development in infants and children.

PMID- 16442176
TI  - The influence of developmental coordination disorder and attention deficits on
      associated movements in children.
AB  - The relationship between associated movements (AMs) and level of motor
      performance is not well understood. In this study we investigated whether
      children with developmental coordination disorder (DCD), with (n = 10) and
      without (n = 10) attention deficit hyperactivity disorder (ADHD), and a control
      group (n = 10), differed in the severity of AMs. A total AM severity score was
      obtained for each child by rating their performance on AM tasks. Both groups with
      motor difficulties had significantly more severe AMs than the control group. A
      significant correlation was found between level of motor performance and total AM
      scores (r = -.62). Our results suggest that level of motor performance should be
      considered in future research attempting to understand individual differences in
      severity of AMs as a function of motor, learning, and behavioural disorders.

PMID- 16442177
TI  - Responsiveness to terrestrial optic flow in infancy: does locomotor experience
      play a role?
AB  - Human infants show a peak in postural compensation to optic flow at approximately
      nine months of age. The current experiment tested whether the magnitude of visual
      postural coupling in 9-month-olds increases when terrestrial optic flow is added
      to a moving room. A secondary objective was to explore whether locomotor
      experience plays any role in enhancing responsiveness to the additional
      terrestrial information. Ninety-one infants (experienced creepers, nascent
      creepers, and prelocomotors) were exposed to two conditions of optic flow: global
      optic flow (G) and global optic flow minus terrestrial optic flow (G-T). The
      additional terrestrial optic flow led to significantly higher visual-postural
      coupling. Consistent with previous findings, locomotor experience had no effect
      on responsiveness to the G-T condition, though there was weak evidence that the
      nascent creepers were more strongly influenced by the difference between flow
      conditions than the other infants. Unexpectedly, the prelocomotor females showed
      significantly lower visual-postural coupling than the prelocomotor males. These
      findings support the notion that the ground provides an important source of
      information for the control of posture and locomotion. The findings also suggest
      that locomotor experience most likely helps to functionalize smaller (partial),
      rather than larger (global), optic flow fields for postural control.

PMID- 16442178
TI  - Lipopolysaccharides-activated human astroglioma cells induce apoptotic death of T
      lymphocytes via c-Jun N-terminal kinases-dependent up-regulation of TRAIL.
AB  - In the present study, we report that activated human astroglioma cells can injure
      T-lymphocytes by producing tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL). Treatment with lipopolysaccharides (LPS), a well-known immune
      stimulator, increased the expression levels of TRAIL mRNA and protein in human
      astroglioma cells. The increase of TRAIL mRNA expression by LPS was preceded by
      phosphorylation of the c-Jun N-terminal kinase (JNK) and consequently abrogated
      in the presence of the specific JNK inhibitor SP600125. The up-regulation of
      TRAIL expression was well co-related with AP-1 activation. Activated human
      astroglioma cells markedly induced the apoptotic death of T-lymphocytes. Pre
      treatment with the TRAIL antagonistic protein TRAIL-R2:Fc prevented the death of
      T-lymphocytes caused by activated human astroglioma cells. The present results
      suggest that astroglioma cells may down-regulate T-lymphocytes via up-regulation
      of TRAIL.

PMID- 16442180
TI  - Engineered riboswitches as novel tools in molecular biology.
AB  - During the last years the great importance of RNA for regulating gene expression
      in all organisms has become obvious. Consequently, several recent approaches aim
      to utilize the outstanding chemical properties of RNA to develop artificial RNA
      regulators for conditional gene expression systems. A combination of rational
      design, in vitro selection and in vivo screening systems has been used to create
      a versatile set of RNA based molecular switches. These tools rely on diverse
      mechanisms and exhibit activity in several organisms. In this review, we
      summarize recent developments in the application of engineered riboswitches for
      gene regulation in vivo.

PMID- 16442179
TI  - Peripheral clock gene expression in CS mice with bimodal locomotor rhythms.
AB  - CS mice show unique properties of circadian rhythms: unstable free-running
      periods and distinct bimodal rhythms (similar to rhythm splitting, but hereafter
      referred to as bimodal rhythms) under constant darkness. In the present study, we
      compared clock-related gene expression (mPer1, mBmal1 and Dbp) in the SCN and
      peripheral tissues (liver, adrenal gland and heart) between CS and C57BL/6J mice.
      In spite of normal robust oscillation in the SCN of both mice, behavioral rhythms
      and peripheral rhythms of clock-related genes were significantly different
      between these mice. However, when daytime restricted feeding was given, no
      essential differences between the two strains were observed. These results
      indicate that unusual circadian behaviors and peripheral gene expression in CS
      mice do not depend on the SCN but rather mechanisms outside of the SCN.

PMID- 16442181
TI  - Serum adiponectin is associated with fasting serum C-peptide in non-obese
      diabetic patients.
AB  - Circulating adiponectin (ADP) level in diabetic patients was mainly studied from
      a viewpoint of insulin action, with little being known about the regulation by
      pancreatic beta-cell function. We thus investigated the relationship between the
      serum ADP concentration and pancreatic beta-cell function in non-obese [body mass
      index (BMI) <30 kg/m(2)] diabetic patients. Serum ADP was measured in 239 type 2
      diabetic patients, 61 type 1 diabetic patients and 159 non-obese and non-diabetic
      subjects with enzyme-linked immunosorbent assay. Serum ADP was analyzed
      separately by gender. In both males and females, the ADP level increased in
      conjugation with beta-cell dysfunction, estimated by fasting serum C-peptide, and
      showed marked increase in type 1 diabetic patients. Multivariate analysis in type
      2 diabetic patients showed that the fasting serum C-peptide was extracted as an
      independent and significantly negative modulator for serum ADP in addition to
      BMI. The ADP level was not associated with the daily dose of injected insulin in
      the multivariate analysis using insulin treated patients with types 1 and 2
      diabetes. These results indicate that pancreatic beta-cell function is one of a
      significant negative modulator for the circulating ADP level in non-obese
      diabetic patients and support the presence of an adipoinsular axis.

PMID- 16442183
TI  - Removal of PCB-DNAPL from a rough-walled fracture using alcohol/polymer flooding.
AB  - Phase behaviour experiments employing PCB (Aroclor 1242)/alcohol/water systems
      were conducted with ethanol (EtOH) and n-propanol (nPA). Both exhibited an
      affinity for the aqueous phase within the entire two-phase region. As much as 88%
      by volume (88% vol.) EtOH and 80% vol. nPA were necessary to achieve full
      miscibility of the PCB in the aqueous phase. DNAPL-water interfacial tension
      (IFT) was reduced from 38.9 dyn/cm to 4.7 dyn/cm and 2.4 dyn/cm with 80% vol.
      EtOH and 76% vol. nPA. The addition of alcohol brought about 41% and 54%
      reductions in DNAPL viscosity at maximal concentrations of EtOH and nPA. Density
      of the PCB-DNAPL was relatively unaffected by the presence of alcohol. A series
      of seven experiments were conducted where successive slugs of nPA and xanthan gum
      polymer solutions were injected into a fractured shale sample. A 30% vol. nPA
      solution injected under a hydraulic gradient of 0.36 allowed enhanced PCB removal
      primarily through reduction of IFT and resulted in 72% DNAPL recovery. Several
      pore volumes of alcohol solution were necessary to displace all the potentially
      mobile non-wetting phase since the high-viscosity DNAPL was mobilized at a lower
      flow rate than the overall fluid velocity, illustrating non-piston displacement.
      The injection of a 95% vol. nPA alcohol solution, theoretically at a sufficient
      concentration to produce fully miscible displacement of the residual DNAPL at
      equilibrium, resulted in non-equilibrium partitioning of the PCB into the
      flushing solution, likely due to the high fluid velocities in the fracture. The
      injection of 200 pore volumes of 95% vol. nPA solution resulted in 94% DNAPL
      recovery. Alcohol floods operated below the miscibility envelope appear to be a
      valuable source zone remedial alternative where the objective is to reduce DNAPL
      mobility to zero, but it should be noted that DNAPL mobility is increased during
      the application of the technology and steps may need to be taken to prevent
      unwanted vertical mobilization.

PMID- 16442182
TI  - Chemotactic cytokine receptor 5 (CCR5) gene promoter polymorphism (59029A/G) is
      associated with diabetic nephropathy in Japanese patients with type 2 diabetes: a
      10-year longitudinal study.
AB  - We previously showed that polymorphisms of the promoter area of chemokine
      receptor 5 (CCR5) gene (59029G/A) and its agonist, regulated upon activation,
      normal T-cell expressed and secreted (RANTES) gene (-28C/G) were new candidates
      for susceptibility to diabetic nephropathy. The aim of this study was to confirm
      the effect of these polymorphisms on the development and progression of diabetic
      nephropathy. We performed a 10-year retrospective study of 191 Japanese type 2
      diabetic patients with normoalbuminuria at baseline. The subjects were classified
      into two groups: (1) those with persistent normoalbuminuria (group N) and (2)
      those with progression from normoalbuminuria to microalbuminuria or overt
      proteinuria (group P). Then, their association with CCR5 59029G/A and RANTES 
      28C/G polymorphisms was assessed. The frequency of the RANTES -28G(+) genotype
      did nor differ between the two groups, but the CCR5 59029A(+) genotype had a
      significantly higher frequency in group P than in group N (83% versus 71%,
      p=0.04). By discriminant analysis, only the CCR5 59029A(+) genotype showed an
      independent positive correlation with the onset or progression of nephropathy
      (p=0.03, odds ratio=2.41, 95% CI=1.09-5.33). Therefore, the CCR5 59029A(+)
      genotype seems to be related the etiology of diabetic nephropathy in Japanese
      type 2 diabetics.

PMID- 16442184
TI  - Up-regulation of connexin43 correlates with increased synthetic activity and
      enhanced contractile differentiation in TGF-beta-treated human aortic smooth
      muscle cells.
AB  - Up-regulation of the gap-junctional protein connexin43 (Cx43) in arterial smooth
      muscle cells (SMCs) features in response to injury and in atherosclerosis, in
      parallel with phenotypic transition to the synthetic state. TGF-beta1 is known to
      have a role in SMC differentiation and extracellular matrix (ECM) synthesis, key
      characteristics of phenotypic state. Here, we set out to examine the effects of
      TGF-beta1 on Cx43-gap junction expression in relation to SMC differentiation, ECM
      synthesis and growth. Cx43 expression was analysed by immunoconfocal microscopy
      and Western blotting in primary human aortic SMCs treated with TGF-beta1 over a
      48-h period, with assessment of gap-junctional communication by cell-to-cell
      transfer of microinjected ethidium bromide. In parallel, synthetic activity was
      analysed by Northern blotting for ECM components alpha-1(I) and alpha1(III)
      procollagen transcripts, contractile differentiation was assessed by
      immunoconfocal microscopy and Western blotting of the markers smooth muscle alpha
      actin, calponin and smooth muscle heavy chain isoform 1 (SM1), and growth was
      measured by BrdU incorporation. Our results demonstrate that TGF-beta1
      significantly up-regulates Cx43 expression and intercellular communication, in
      concert with increased expression of alpha-actin, calponin and SM1. Concomitant
      with contractile protein expression, ECM synthesis was increased rather than
      decreased, TGF-beta1 inducing a significant up-regulation of both procollagen
      transcripts. These effects were independent of growth. We conclude that in human
      aortic SMCs, TGF-beta1 treatment leads to up-regulation of Cx43-mediated gap
      junctional communication and increased synthetic activity yet, somewhat
      paradoxically, also enhanced contractile differentiation.

PMID- 16442185
TI  - Characterization of the phenolic constituents in Mauritian endemic plants as
      determinants of their antioxidant activities in vitro.
AB  - The phenolic constituents of Mauritian endemic plants from the Rubiaceae and
      Myrtaceae family were assessed and correlated with their potential antioxidant
      activities in vitro. The antioxidant activities of the plant extracts ranged from
      0.27 to 1.49mmol Trolox equivalent/g FW and from 0.20 to 1.39mmol Fe(II)
      equivalent/g FW in the TEAC and FAP assays, respectively, with Syzygium
      commersonii showing the highest activity in these two systems. Eugenia orbiculata
      and all the Syzygium species were effective scavengers of hypochlorous acid while
      Monimiastrum acutisepalum was the most potent inhibitor of deoxyribose
      degradation. The plant extracts inhibited microsomal lipid peroxidation with low
      IC(50)s ranging from 0.02 to 1.75mgFW/mL when reaction was initiated with
      Fe(3+)/ascorbate and from 0.093 to 1.55mgFW/mL in the AAPH-dependent lipid
      peroxidation. The potential prooxidant nature of the plant extracts was compared
      with ascorbate (250microM) using copper-phenanthroline assay. The plant extracts
      at concentrations up to 5gFW/L were not prooxidant. However, Myonima nitens,
      Syzygium commersonii, Syzygium glomeratum and Syzygium mauritianum at
      concentrations of 10gFW/L had potency approaching 50% of the prooxidant activity
      of ascorbic acid in vitro, suggesting relative safeties. The total phenolics
      influenced the antioxidant activities in the TEAC, FRAP and HOCl scavenging
      assays whereas a negative correlation was observed with the deoxyribose assay.
      The high levels of polyphenolic compounds and the significant antioxidant
      activities of these Rubiaceae and Myrtaceae plant family make them suitable
      candidates as prophylactic agent.

PMID- 16442187
TI  - 3D QSAR for GSK-3beta inhibition by indirubin analogues.
AB  - Glycogen synthase kinase 3 (GSK-3) plays an important role in a diverse number of
      regulatory pathways by phosphorylation of several different cellular targets and
      its inhibitors have been evaluated as promising drug candidates. Indirubin
      analogues show favorable inhibitory activity targeting GSK-3beta, which is
      closely related to the property and position of substituents. Two methods were
      used to build 3D-QSAR models for indirubin derivatives. The conventional 3D-QSAR
      (ligand-based) studies were performed based on the lower energy conformations
      employing atom fit alignment rule. The receptor-based 3D-QSAR models were also
      derived using bioactive conformations obtained by docking the compounds to the
      active site of GSK-3. Conclusions of models based on two methods are similar and
      reliable. The results indicate that both ligand-based and receptor-based are
      feasible tools to build 3D-QSAR models. Contour maps of the receptor-based CoMSIA
      model (q(2) = 0.766, r(2) = 0.908, N (number of components) = 5) including the
      steric, electronic and hydrophobic fields were taken as representative to explain
      factors affecting activities of inhibitors.

PMID- 16442186
TI  - Determinants of platelet activation in Alzheimer's disease.
AB  - OBJECTIVES: To investigate the rate of platelet thromboxane (TX) biosynthesis and
      its determinants in Alzheimer's disease. METHODS AND RESULTS: A cross-sectional
      comparison of urinary 11-dehydro-TXB(2) and 8-iso-prostaglandin (PG)F(2alpha)
      (markers of in vivo platelet activation and lipid peroxidation, respectively),
      plasma Vitamin E, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6, was carried-out in 44 Alzheimer patients and 44 matched
      controls. To investigate the cyclooxygenase (COX)-isoform involved in TXA(2)
      biosynthesis, nine Alzheimer patients were treated with low-dose aspirin
      (100mg/d) or rofecoxib (25mg/d) for 4 days. Urinary 11-dehydro-TXB(2) and 8-iso
      PGF(2alpha) were significantly higher in Alzheimer patients than in controls
      (Median: 1983.5 versus 517.5pg/mg creatinine and 938.5 versus 304.0pg/mg
      creatinine, p<0.0001, respectively), with a significant correlation between the
      two metabolites (rho=0.75, p<0.0001). An inverse correlation was observed between
      Vitamin E and both urinary metabolites (8-iso-PGF(2alpha): R(s)=-0.51, p=0.0004;
      11-dehydro-TXB(2): R(s)=-0.44, p=0.0026) in Alzheimer patients. No difference was
      found in CRP, TNF-alpha and IL-6 levels between the two groups. Urinary 11
      dehydro-TXB(2) was significantly reduced by aspirin, but not by rofecoxib,
      consistently with a COX-1-mediated TXA(2) biosynthesis. 8-iso-PGF(2alpha)
      excretion was not modified by either COX-inhibitor, consistently with its oxygen
      radical-catalyzed formation. CONCLUSIONS: Platelet activation is persistently
      enhanced in Alzheimer's disease. This is related, at least in part, to increased
      lipid peroxidation associated with inadequate levels of Vitamin E.

PMID- 16442188
TI  - Synthesis and biological activity of 6H-isoindolo[2,1-a]indol-6-ones, analogues
      of batracylin, and related compounds.
AB  - Closely related to batracylin, 6H-isoindolo[2,1-a]indol-6-ones including 2-nitro-
      13a, 2-amino- 14, and 2-diethylaminopropionamide derivative 16 as well as D-ring
      substituted 13b, 13c or A-ring substituted 13d and 20 analogues, were synthesised
      and evaluated against L1210 leukaemia. Subsequent treatment of 13b and 13c with
      N,N-diethylethylenediamine at 180 degrees C, led to compounds 17a and 17b arising
      from an unexpected opening of the pyrrolidinone ring and amidification of the
      keto group. Under the same conditions, the dichloro derivative 13d led to the
      monoalkyl compound 20 which was the most cytotoxic of the series.

PMID- 16442189
TI  - [Lupus erythematosus misleads left atrial myxoma's diagnosis].

PMID- 16442190
TI  - [A painful knee].

PMID- 16442191
TI  - Radial shift of the ulnar fingers: a new technique for special cases of
      longitudinal central deficiency.
AB  - Treatment of central longitudinal deficiencies is well defined, with different
      techniques established for the classical clefts. However, none of these
      techniques is easily applied to the treatment of very deep clefts accompanied by
      a significant divergence of the metacarpal bones. In such cases, the results of
      current techniques are disappointing. We propose a new technique of
      "Translocation in the Radial direction of the Ulnar Finger(s)" (TRUF) by intra
      carpal osteotomy. The results are illustrated in three clinical cases. The TRUF
      operation allowed closing of the cleft, alignment of the metacarpal bones and
      preservation of carpometacarpal mobility. When necessary, a metacarpal synostosis
      may be treated at the same procedure.

PMID- 16442192
TI  - The gray platelet syndrome: clinical spectrum of the disease.
AB  - The gray platelet syndrome (GPS) is a rare inherited disorder of the
      megakaryocyte (MK) lineage. Thrombocytopenia and enlarged platelets are
      associated with a specific absence of alpha-granules and their contents. GPS
      patients exhibit much heterogeneity both in bleeding severity and in their
      response to platelet function testing. A unique feature is that proteins
      endogenously synthesised by megakaryocytes (MK) or endocytosed by MK or platelets
      fail to enter into the secretable storage pools that characterise alpha-granules
      of normal platelets. Although the molecular basis of the disease is unknown,
      evidence suggests that alpha-granules simply fail to mature during MK
      differentiation. One result is a continued leakage of growth factors and
      cytokines into the marrow causing myelofibrosis. While for some patients platelet
      function may be only moderately affected, for others thrombin and/or collagen
      induced platelet aggregation is markedly modified and an acquired lack of the
      GPVI collagen receptor has been reported. In this review, we document the
      clinical and molecular heterogeneity in GPS, a unique disease of the biogenesis
      of platelet alpha-granules and of the storage of growth factors and secretable
      proteins.

PMID- 16442193
TI  - An approach to the validation of biomarkers of harm for use in a tobacco context.
AB  - There is both a call and a need for biomarkers of harm that are validated for use
      in a tobacco context. Currently, there are no validated biomarkers and there is
      no consensus about which ones may be suitable for this purpose. To advance the
      science in this area a working definition of biomarkers of harm and a shortlist
      of candidate biomarkers are proposed. A framework for the validation of
      biomarkers of harm using of a series of epidemiological studies culminating in a
      targeted prospective study is outlined. The candidate biomarkers have advanced to
      preliminary testing although this does not imply that any on the shortlist will
      become validated. This framework could also be used for the evaluation of
      proteomic, genomic, transcriptosomic or metabonomic profiles, which may turn out
      to be the preferred biomarkers for use in harm prediction. Biomarker studies
      would complement data that are generated from specific in vitro tests and from
      animal studies to evaluate tobacco products.

PMID- 16442194
TI  - Manic/hypomanic symptoms induced by atypical antipsychotics: a review of the
      reported cases.
AB  - The widespread use of atypical antipsychotics (APs) in clinical practice has
      advanced the pharmacotherapy of schizophrenia regarding treatment resistant cases
      as well as the negative symptoms of the disorder. Atypical antipsychotics
      manifest a favourable side effect profile compared to the conventional APs.
      Atypical APs are also being used as adjunct therapy or monotherapy in patients
      with manic episodes of bipolar and schizoaffective disorder as well as in
      patients with psychotic (delusional) depression. On the other hand, atypical APs
      are also used in combination with (selective) serotonin reuptake inhibitors [(S)
      SRIs] in the treatment of resistant depression. Shortly after the introduction of
      atypical APs several cases of manic/hypomanic symptoms during treatment with
      these compounds have been described in the literature. The reported cases and the
      possible pathogenetic mechanisms involved in their occurrence are reviewed and
      discussed.

PMID- 16442195
TI  - Community dysfunction in schizophrenia: rate-limiting factors.
AB  - The purpose of the present study was to investigate the impact of cognitive
      functioning, psychopathology, and severity of extrapyramidal side effects on
      community outcome in a group of Greek outpatients with schizophrenia.
      Participants were 40 outpatients with schizophrenia (25 men). Social adjustment
      was assessed with the Quality of Life Scale (QLS). Severity of symptoms of
      schizophrenia was measured with the Positive and Negative Syndrome Scale (PANNS),
      and extrapyramidal symptoms with the Extrapyramidal Symptom Rating Scale (ESRS).
      Finally, a battery of neuropsychological tests was administered in order to
      assess the following cognitive domains: executive functioning/set shifting,
      executive functioning/inhibition, fluency, verbal memory, visual memory, working
      memory, attention, visuospatial ability, and psychomotor speed/visual scanning.
      Total scores on the QLS were significantly correlated with negative symptoms,
      parkinsonism, and performance on the fluency tasks. Interpersonal relations
      subscale was significantly related with negative symptoms and fluency. No
      significant relationship was found between the Instrumental Role Functioning
      subscale and the PANSS, ESRS, or any cognitive domain. Scores on the Intrapsychic
      Foundation subscale were significantly correlated with negative symptoms and
      fluency. Finally, scores on the Common Objects and Activities subscale were
      significantly related with severity of negative symptoms, parkinsonism and visual
      memory. Our findings suggest that severity of negative symptoms, cognitive
      dysfunction, especially performance on fluency tasks and visual memory, as well
      as parkinsonism, are important determinants of functional outcome in
      schizophrenia.

PMID- 16442196
TI  - Verbal memory deficits in a preadolescent case of lesions of the left
      parahippocampal gyrus associated with a benign tumor.
AB  - The authors report cognitive functions of a 13-year-old boy with a cavernous
      angioma occupying the posterior left parahippocampal gyrus (PHG) and part of the
      left fusiform gyrus but not hippocampus. Neuropsychological examinations soon
      after the removal of the tumor showed selective deficits in semantic memory
      function, as evaluated by the Category Fluency Task and the Wechsler Memory Scale
      Revised, while visual memory, attention, and IQ were not affected. These
      observations suggest the involvement of the PHG in the processing of semantic
      memory and provide an insight into the neural substrates underlying the distinct
      cognitive deficits in some of the psychiatric diseases such as schizophrenia.

PMID- 16442197
TI  - Sub-chronic antipsychotic drug treatment does not alter brain phospholipid fatty
      acid composition in rats.
AB  - Altered membrane phospholipid fatty acid composition is reported in schizophrenia
      and appears to be reduced by antipsychotic drug treatment. To determine whether
      antipsychotic drugs have a direct effect on brain phospholipid fatty acid
      composition, the effects of sub-chronic treatment with a "typical" and an
      "atypical" antipsychotic drug were determined in adult male Sprague-Dawley rats.
      Rats were treated with haloperidol (1 mg/kg), clozapine (20 mg/kg) or vehicle
      daily for 21 days. Whole brain total phospholipid composition was determined by
      gas chromatography. No alterations in brain phospholipid composition were
      produced by either drug. This suggests that the apparent normalization of
      membrane phospholipids observed in drug-treated schizophrenic patients is not due
      to a direct pharmacological effect of these drugs nor can the pharmacological
      effects of these drugs occurring in this time frame be attributed to alterations
      in neuronal membrane fatty acid composition.

PMID- 16442198
TI  - Safety evaluation of short-term exposure to chitooligomers from enzymic
      preparation.
AB  - Chitooligomers have significant application to the development of functional
      foods. This paper evaluated systematically the safety of chitooligomers, which
      were prepared by enzymatic depolymerization of chitosan. The oral maximum
      tolerated dose of this chitooligomes was more than 10 g/kg body weight in mice.
      It had no mutagenicity judged by negative experimental results of Ames test,
      mouse bone marrow cell micronucleus test and mouse sperm abnormality test. A 30
      day feeding study shows that no abnormal symptoms and clinical signs or deaths
      were found in rats during the test. There were no significant difference in body
      weight, food consumption and food availability of rats in each test group. No
      significant differences were found in each hematology value, clinical chemistry
      value and organ/body weight ratio, either. No abnormality of any organ was found
      during histopathological examination. It is concluded that short-term ingestion
      of chitooligomers is of non-toxicity.

PMID- 16442199
TI  - A 13-week subchronic toxicity study of dietary administered morin in F344 rats.
AB  - A subchronic toxicity study of a flavonoid morin was performed in both sexes of
      F344 rats with dietary administration at concentrations of 0%, 0.625%, 1.25%,
      2.5% and 5% (w/w) for 13 weeks. No mortality or abnormal clinical signs were
      observed throughout the experimental period in any group. Although a slight
      tendency for increase in food intake was noted in both sexes of the 2.5% and 5.0%
      groups, slight non-significant body weight decrease was observed in 5.0% males.
      Significant increases in alanine transaminase (ALT; over 2.5%), alkali
      phosphatase (ALP; 1.25% and 5.0%) and relative liver weights (1.25% and 2.5%) in
      males and in gamma-glutamyl transpeptidase (gamma-GT), aspartate transaminase
      (AST), ALT, relative liver weights in the 2.5% and 5.0% females and ALP in 5.0%
      females were noted. Increased urea nitrogen and relative kidney weights at dose
      of 1.25% and above and creatinine at 5.0% were observed also in females. On
      histopathological observation, hepatocyte hypertrophy was detected in 3 of 10
      5.0% females. Based on the above findings, the no-observed-adverse-effect level
      (NOAEL) for both sexes was estimated to be 0.625% (299 and 356 mg/kg b.w./day for
      males and females, respectively).

PMID- 16442200
TI  - Caries experience variables as indicators in caries risk assessment in 6-7-year
      old Chinese children.
AB  - OBJECTIVES: The aim of the present study is to investigate variables of the past
      caries experience as indicators of future caries in a Chinese child population.
      METHODS: Caries was recorded at baseline and 2 years later in 433, 6-7-year-old
      Chinese children. Correlation coefficients between variables of the past caries
      experience and caries increment were calculated. Stepwise logistic regression
      analyses provided predictor variables. ROC curves presenting sensitivity as
      function of (100-specificity) were employed to summarize the obtained
      information. The area under the ROC curves was used as a measure of predictive
      accuracy. RESULTS: Twelve variables of baseline caries experience had a
      significant (p<or=0.05) correlation with caries increment in the permanent
      dentition. Among the variables, the number of primary molars with enamel or
      dentine caries, fillings or missings due to caries (d(12)mftmol), the number of
      fissures of the first permanent molar with enamel caries (D(1)fis) and the number
      of pits and fissures of the first permanent molar with dentine caries
      (D(2)pitfis) were the most powerful caries predictors, which resulted in a value
      of 0.74 under the ROC. CONCLUSIONS: By including non-cavitated caries in the past
      caries experience of primary molars and permanent first molars, it was possible
      to construct a screening criterion (d(12)mftmol+D(1)fis+D(2)pitfis), which
      enabled the selection of true negative children and the selection of a high
      caries risk group in a 6-7-year-old Chinese child population.

PMID- 16442201
TI  - A novel automated waterline cleaning system that facilitates effective and
      consistent control of microbial biofilm contamination of dental chair unit
      waterlines: a one-year study.
AB  - Microbial contamination of dental chair unit (DCU) output water caused by biofilm
      growth in dental unit waterlines (DUWs) is a universal problem and a potentially
      significant source of cross-infection. The microbial quality of output water from
      a Planmeca Compact i DCU equipped with the novel Water Management System (WMS),
      an integrated and automated DUW cleaning system, was investigated over a 12-month
      period with the hydrogen peroxide- and silver ion-containing disinfectants
      Planosil and Planosil Forte. Four weeks after connection to the potable-water
      quality mains supply the density of aerobic heterotrophic bacteria, rose from the
      low levels consistently found in the supply water throughout this study (mean
      average 77 cfu/mL) to 15,400 cfu/mL. Disinfection of DUWs once weekly with
      Planosil for 10 weeks resulted in a dramatic reduction in bacterial density
      immediately following disinfection (mean average 26 cfu/mL). Bacterial density
      rose steadily between disinfections and by 7 days post-disinfection, water
      quality failed (mean average 384 cfu/mL) the American Dental Association DCU
      water quality standard of <or=200 cfu/mL. The DCU was then disinfected once
      weekly for 40 weeks with Planosil Forte. The average bacterial density
      immediately post-disinfection was 20 cfu/mL and 7 days post-disinfection was 113
      cfu/mL. Electron microscopy showed that improved output water quality following
      disinfection with both disinfectants was associated with marked elimination of
      DUW biofilm, but deterioration of water quality following disinfection was
      associated with its regrowth. The most common bacterial species cultured from the
      mains water and the DCU output water were Microcococcus luteus and Sphingomonas
      spp., respectively, the latter of which are known opportunistic pathogens. The
      findings of this study show that the Planmeca Compact i DCU equipped with the
      easy to use and automated WMS, that requires minimal effort on the part of the
      operator, consistently provides output water that passes the ADA quality standard
      of <or=200 cfu/mL for up to 7 days following once-weekly disinfection with
      Planosil Forte.

PMID- 16442202
TI  - The practice of rescaling scalp-recorded event-related potentials.
AB  - In a recent article the principles of and the recommended practices for rescaling
      scalp-recorded electrophysiological data were submitted to a comprehensive review
      [Urbach, T.P., Kutas, M., 2002. The intractability of scaling scalp distributions
      to infer neuroelectric sources. Psychophysiology 39, 791-808]. The authors
      argued, on both conceptual and pragmatic grounds, that the practice of rescaling
      be discontinued when the motivation for rescaling was to infer that at least
      partially non-overlapping brain regions were engaged in two different
      experimental conditions. This article is a response to that proposal, and the key
      observations are that: (1) there remain sound theoretical reasons for rescaling
      when the motivation for rescaling is to infer that not entirely the same
      cognitive processing is engaged in two conditions and (2) at least for certain
      classes of experimental design the pragmatic concerns raised by Urbach and Kutas
      are not sufficient to warrant recommending that rescaling be discontinued.

PMID- 16442203
TI  - Laparoscopic uterine nerve ablation versus vaginal uterosacral ligament resection
      in postmenopausal women with intractable midline chronic pelvic pain: a
      randomized study.
AB  - OBJECTIVE: To assess and compare the laparoscopic uterine nerve ablation (LUNA)
      and the vaginal uterosacral ligament resection (VUSR) in postmenopausal women
      with chronic pelvic pain (CPP). STUDY DESIGN: Eighty postmenopausal women with
      intractable and severe midline CPP were randomized to undergo LUNA or VUSR. Costs
      of two surgical procedures were assesses. Cure rate, severity of CPP, and deep
      dyspareunia were also evaluated after 6 and 12 months from surgery. RESULTS: The
      mean cost of LUNA resulted significantly higher in comparison with VURS (2078+/
      637 versus 1497+/-297, P<0.001). The cure rate was not significantly different
      between the two groups at 6 (33/40, 82.5% versus 35/40, 87.5% for groups A and B,
      respectively; P=0.530; RR 0.94, 95% CI 0.78-1.13), and 12 months (27/36, 75.0%
      versus 28/38, 73.7%, for groups A and B, respectively; P=0.901; RR 0.90, 95% CI
      0.78-1.33) of follow-up. At same times, a significant (P<0.01) decrease in
      severity of CPP and deep dyspareunia was observed in both groups with no
      difference between them. CONCLUSIONS: Both LUNA and VUSR are equally effective
      surgical treatments in postmenopausal women with central CPP but VUNR is
      significantly cheaper than LUNA.

PMID- 16442204
TI  - The Young's modulus of fetal preterm and term amniotic membranes.
AB  - OBJECTIVE: To examine the Young's modulus of the human amniotic membranes, as
      well as its relationship to gestational age. To determine whether cellular and
      material-related parameters affect this modulus. STUDY DESIGN: In a prospective
      study at the Obstetric outpatient clinic of the University Hospital Zurich
      Young's modulus, thickness and mesenchymal:epithelial cell ratio of amniotic
      membranes of preterm (N=23) and term (N=40) placentae were examined. Significance
      (P<0.05) was calculated with the Mann-Whitney two-sample rank sum test and
      Wilcoxon signed rank test, while correlations were made using the Spearman's
      correlation. RESULTS: The Young's modulus of preterm amniotic membranes was
      significantly higher than that of term membranes. It varied within the same
      amniotic membrane. The thickness of the amnion in both preterm and term membranes
      did not differ significantly. The thinner the preterm and term amniotic
      membranes, the higher the Young's modulus was. There was no relation to the
      mesenchymal:epithelial cell ratio in the amnion. CONCLUSIONS: Preterm amniotic
      membranes are stiffer than term amniotic membranes. Tentatively, we hypothesise
      that there may be a correlation between the extracellular matrix components and
      the elastic properties of the membrane.

PMID- 16442205
TI  - Intake of selected micronutrients and the risk of surgically treated benign
      prostatic hyperplasia: a case-control study from Italy.
AB  - OBJECTIVE: To analyze the relationship between surgically treated benign
      prostatic hyperplasia (BPH) and intake of selected micronutrients. METHODS: A
      multicentric case-control study was conducted in Italy between 1991 and 2002.
      Cases were 1369 men with histologically confirmed, surgically treated BPH and
      controls were 1451 men younger than 75 yr, frequency matched by quinquennium of
      age and study center, admitted to the hospital for acute nonneoplastic diseases.
      Information was collected by trained interviewers using a structured validated
      food-frequency questionnaire. The odds ratios (ORs) and 95% confidence intervals
      (CIs) were estimated by unconditional multiple logistic regression models.
      RESULTS: The risk of BPH significantly decreased with increasing intake of
      carotene (OR=0.80 for an increment equal to the difference between the 80th and
      20th percentile of intake), alpha-carotene (OR=0.83), beta-carotene (OR=0.82),
      and cis beta-carotene (OR=0.82) and tended to decrease with the intake of vitamin
      C (OR=0.89) and iron (OR=0.79). The OR tended to increase with the intake of
      sodium (OR=1.30) and zinc (OR=1.10). No systematic heterogeneity was observed
      across strata of age, education, and body mass index. No meaningful associations
      emerged for other antioxidants, such as folic acid, lycopene, lutein/zeaxanthin,
      vitamin E, vitamin D, nor for retinol. CONCLUSIONS: Our results suggest a
      protective effect of carotene on the risk of BPH. The risk tended to decrease
      also with the intake of vitamin C and iron and tended to increase with the intake
      of sodium and zinc. Results also indicate that other antioxidants, including
      folic acid, lycopene, lutein/zeaxanthin, and vitamins D and E, and retinol were
      not related to the risk for this disease.

PMID- 16442206
TI  - Short-course radiotherapy (RT) for metastatic spinal cord compression (MSCC) due
      to renal cell carcinoma: results of a retrospective multi-center study.
AB  - OBJECTIVE: For MSCC treatment, a short treatment time is desirable, especially if
      survival prognosis is poor. Survival depends on the primary tumor, extent of
      disease, performance status, ambulatory status, and the number of involved
      vertebrae. These factors may help to define the appropriate regimen for the
      individual patient. Our study compares short-course (1 x 8 Gy, 5 x 4 Gy) and long
      course RT (10 x 3 Gy, 15 x 2.5 Gy, 20 x 2 Gy) for functional outcome in MSCC
      patients with renal cell carcinoma. METHODS: The following potential prognostic
      factors for functional outcome were retrospectively investigated: age,
      performance status, involved vertebra, ambulatory status, time of developing
      motor deficits before RT, radiation schedule (short-course RT, n=37; long-course
      RT, n=50). RESULTS: Eighty-seven patients were included in this retrospective
      study, 25 patients (29%) showed improvement of motor function, 52 patients (60%)
      no change, 10 patients (11%) deterioration. 25% of non-ambulatory patients became
      ambulatory after RT. Functional outcome was affected by the time of developing
      motor deficits before RT (p<0.001). The RT schedule had no significant impact
      (p=0.91). In the short-course RT sub-group, functional outcome was similar for 1
      x 8 Gy and 5 x 4 Gy (p=0.99). CONCLUSION: Short-course and long-course RT appear
      similarly active for MSCC in patients with renal cell carcinoma. Short-course RT
      appears preferable, as it is means less patient discomfort. Because 1 x 8 Gy and
      5 x 4 Gy were comparably effective, 1 x 8 Gy may be suggested the best actual
      choice.

PMID- 16442207
TI  - 2004 WHO classification of the renal tumors of the adults.
AB  - BACKGROUND: The recently introduced 2004 World Health Organisation (WHO)
      classification of the adult renal epithelial neoplasms is meant to replace the
      previous 1998 WHO classification. METHODS AND RESULTS: The 2004 WHO
      classification is based on pathology and genetic abnormalities. The description
      of categories has been expanded to improve their recognition and new diagnostic
      categories are included. Emphasis has been placed on defining familial renal
      cancer, carcinoma associated with Xp11 translocations, carcinoma associated with
      neuroblastoma, multilocular cystic renal cell carcinoma, tubular, mucinous and
      spindle cells carcinoma; and mixed epithelial and stromal tumour. The potentially
      aggressive epithelioid angiomyolipoma is recognised. CONCLUSIONS: Recognising
      these categories may have important implications in patients' clinical
      management.

PMID- 16442208
TI  - Predicting recurrence and progression in individual patients with stage Ta T1
      bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from
      seven EORTC trials.
AB  - OBJECTIVES: To provide tables that allow urologists to easily calculate a
      superficial bladder cancer patient's short- and long-term risks of recurrence and
      progression after transurethral resection. METHODS: A combined analysis was
      carried out of individual patient data from 2596 superficial bladder cancer
      patients included in seven European Organization for Research and Treatment of
      Cancer trials. RESULTS: A simple scoring system was derived based on six clinical
      and pathological factors: number of tumors, tumor size, prior recurrence rate, T
      category, carcinoma in situ, and grade. The probabilities of recurrence and
      progression at one year ranged from 15% to 61% and from less than 1% to 17%,
      respectively. At five years, the probabilities of recurrence and progression
      ranged from 31% to 78% and from less than 1% to 45%. CONCLUSIONS: With these
      probabilities, the urologist can discuss the different options with the patient
      to determine the most appropriate treatment and frequency of follow-up.

PMID- 16442209
TI  - Prostate biopsy and optimization of cancer yield.

PMID- 16442210
TI  - Laparoscopic and robotic assisted radical prostatectomy--critical analysis of the
      results.
AB  - OBJECTIVE: To evaluate the role of laparoscopic radical prostatectomy (LRP) and
      robotic assisted radical prostatectomy (RLRP) based on personal experience and a
      review of the literature. MATERIAL AND METHODS: Own experience at one European
      and one American LRP-center includes more than 2000 cases. We performed a MEDLINE
      search reviewing the literature on LRP and RLRP between 1992 and 2005 with
      special emphasis on historical aspects, technical considerations, comparison to
      open retropubic (RRP) and perineal radical prostatectomy (PRP), laparoscopic
      training, and the cost-efficiency of the techniques. RESULTS: Based on
      sophisticated training programs a continuous dissemination of the technique took
      place. In the United States, this process was accelerated by the use of the
      daVinci-robot. There is a trend towards the extraperitoneal access. Mid-term
      outcomes of LRP achieved equivalence to open surgery with regards to
      complications, oncologic and functional results. Distinct advantages of LRP
      include less postoperative pain, lower rate of complications, shorter
      convalescence, and better cosmesis. In contrast to RLRP, LRP may reach cost
      equivalence with open surgery (i.e. by reduction of OR-time, use of multi-usable
      instruments). CONCLUSIONS: LRP reproduces the excellent results of open surgery
      providing the advantages of minimal access. Video-assisted teaching improves the
      transfer of anatomical knowledge and technical knowhow. In contrast the United
      States, the use of robots is likely to remain limited in Europe.

PMID- 16442211
TI  - Comparison of the cardiovascular effects of tamsulosin oral controlled absorption
      system (OCAS) and alfuzosin prolonged release (XL).
AB  - OBJECTIVE: The cardiovascular (CV) effects of tamsulosin oral controlled
      absorption system (OCAS) 0.4 mg were compared with those of alfuzosin prolonged
      release (XL) 10 mg. METHODS: Two single-dose, crossover studies were performed.
      In study 1, CV alpha1-adrenoceptor antagonism was assessed by measuring the
      inhibition of phenylephrine (PE)-induced increases in diastolic blood pressure
      (DBP) and total peripheral resistance (TPR) before and after dosing with placebo,
      tamsulosin OCAS, and alfuzosin XL in 18 young subjects. In study 2, orthostatic
      stress tests (OTs) were performed before and after dosing with tamsulosin OCAS
      and alfuzosin XL in 40 elderly subjects. Pharmacokinetics were assessed in both
      studies. RESULTS: In study 1, tamsulosin OCAS induced statistically significantly
      less inhibition of PE-induced increases in DBP at 2 h after dosing and in TPR at
      2 and 4 h after dosing than alfuzosin XL. In study 2, tamsulosin OCAS had a lower
      incidence of positive OTs than did alfuzosin XL, with the difference between both
      treatments being statistically significant at 6h after dosing and for all time
      points after dosing combined. This was in line with smaller changes in vital
      signs observed for tamsulosin OCAS. The t(max) values for both treatments were
      comparable. CONCLUSIONS: Tamsulosin OCAS 0.4 mg produces smaller vascular effects
      than does alfuzosin XL 10 mg.

PMID- 16442212
TI  - Does PSA velocity predict prostate cancer in pre-screened populations?
AB  - PSA-driven screening has been applied to a large part of the male population in
      many countries. An elevated PSA in secondary screens may indicate benign
      enlargement of the prostate rather than prostate cancer. In such cases the yearly
      rate of increase of PSA (PSA velocity [PSAV]) may improve the test
      characteristics of PSA. MATERIALS AND METHODS: Data from the European Randomized
      Study of Screening for Prostate Cancer Rotterdam are used to study the issue.
      Relative sensitivity, relative specificity, and positive predictive value (PPV)
      are calculated. Logistic regression analysis is used to compare odds ratios for
      positive biopsies. The relationship between PSAV and parameters of tumour
      aggressiveness is investigated. RESULTS: Five hundred eighty-eight consecutive
      participants were identified who presented at their first screening with PSA
      values <4.0 and who progressed to PSA values >4.0 ng/ml four years later. None
      were biopsied in round one, all were biopsied in round two. Relative sensitivity
      and specificity depend strongly on PSAV cut-offs of 0.25-1.0 ng/ml/yr. The use of
      PSAV cut-offs does not improve the PPV of the PSA cut-off of 4.0 ng/ml, nor do
      any of the PSAV cut-offs improve the odds ratio for identifying prostate cancer
      with respect to the cut-off value of 4.0 ng/ml. The rate of aggressive cancers
      seems to increase with increasing PSAV. CONCLUSIONS: PSAV does not improve the
      detection characteristics of a PSA cut-off of 4.0 ng/ml in secondary screening
      after four years.

PMID- 16442213
TI  - Factors influencing synonymous codon and amino acid usage biases in Mimivirus.
AB  - Synonymous codon and amino acid usage biases have been investigated in 903
      Mimivirus protein-coding genes in order to understand the architecture and
      evolution of Mimivirus genome. As expected for an AT-rich genome, third codon
      positions of the synonymous codons of Mimivirus carry mostly A or T bases. It was
      found that codon usage bias in Mimivirus genes is dictated both by mutational
      pressure and translational selection. Evidences show that four factors such as
      mean molecular weight (MMW), hydropathy, aromaticity and cysteine content are
      mostly responsible for the variation of amino acid usage in Mimivirus proteins.
      Based on our observation, we suggest that genes involved in translation, DNA
      repair, protein folding, etc., have been laterally transferred to Mimivirus a
      long ago from living organism and with time these genes acquire the codon usage
      pattern of other Mimivirus genes under selection pressure.

PMID- 16442214
TI  - New approaches for male fertility control: HE6 as an example of a putative
      target.
AB  - Reversible contraceptive methods for males are still not available. During the
      last few years several marketing studies have clearly shown that men and women
      would welcome a situation where men could assume responsibility for family
      planning. Schering AG and Organon are currently collaborating to develop a
      hormonal method for male fertility control based on the combination of
      etonogestrel as gestagenic component and testosterone undecanoate. To further
      optimize male contraceptives in terms of improved efficiency, rapid onset,
      reversibility, fewer side effects and a convenient method of application, a
      search for innovative non-hormonal approaches was started. During the last few
      years, numerous proteins were identified which play a specific role in male
      fertility. These proteins have first to fulfil a set of indication-specific
      criteria before a drug discovery process can be initiated. The most important
      criteria for a putative target protein are tissue-selective expression, crucial
      biological function in fertility, drugable properties and feasibility of assay
      development for high-throughput-screening and lead optimization. The G-protein
      coupled receptor HE6 was selected as target and the above selection criteria were
      applied. HE6 displays a preferred epididymis-specific expression pattern and
      belongs to the superfamily of GPCRs, which are well known to be drugable with
      small molecules. A knockout mouse was generated which revealed an infertility
      phenotype with the onset occurring 6 weeks after initiation of spermatogenesis at
      the latest. Surprisingly, no epididymis-specific phenotype was observed. Instead,
      the reabsorption of testicular fluid along the efferent ducts was strongly
      affected. No further obvious side effects were observed in male or female mice.
      This study with HE6 exemplifies how targets for male contraception have to be
      validated before drug development can start.

PMID- 16442216
TI  - Equilibrium and kinetics studies for the adsorption of direct and acid dyes from
      aqueous solution by soy meal hull.
AB  - This paper deals with the application of Soy Meal Hull (SMH), an agricultural by
      product, for the removal of direct and acid dyes from aqueous solutions. Four
      textile dyes, C.I. Direct red 80 (DR80), C.I. Direct red 81 (DR81), C.I. Acid
      blue 92 (AB92) and C.I. Acid red 14 (AR14) were used as model compounds. Physical
      characteristics of SMH such as surface area, Fourier transform infra-red (FTIR)
      and scanning electron microscopy (SEM) were obtained. The surface area of SMH was
      found to be 0.7623 m(2)/g and the presence of functional groups such as hydroxyl,
      amine and carbonyl groups were detected. The effect of initial dye concentration,
      pH, contact time and SMH doses were elucidated at 20+/-1 degrees C. Results show
      that the pH value of 2 is favorable for the adsorption of all four dyes. The data
      evaluated for compliance with the Langmuir, Freundlich and BET isotherm models.
      It was found that data for DR80 and DR81 fitted well with Langmuir isotherm, for
      AB92, BET isotherm is preferred, while for AR14, the Freundlich isotherm is the
      most applicable. The adsorption capacities of SMH for DR80, DR81, AB92 and AR14
      were, 178.57, 120.48, 114.94 and 109.89 mg/g of adsorbent, respectively. Also,
      adsorption kinetics of dyes was studied and the rates of sorption were found to
      conform to pseudo-second order kinetics with good correlation (R(2)> or =0.9977).
      Maximum desorption of > or =99.8% was achieved for DR80, DR81 and AB92 and 86%
      for AR14 in aqueous solution at pH 10. Based on the data of present
      investigation, one could conclude that the SMH being a natural, eco-friendly and
      low-cost adsorbent with relatively large adsorption capacity might be a suitable
      local alternative for elimination of dyes from colored aqueous solutions.

PMID- 16442215
TI  - Electrothermal atomic absorption spectrometric determination of total and
      hexavalent chromium in atmospheric aerosols.
AB  - A method was developed which allow separate determination of Cr(VI) and total Cr
      from the same minute sample of atmospheric aerosols. Cr(VI) was leached was with
      0.1M Na(2)CO(3) and the total Cr concentrations were determined after acid
      digestion. The method was validated by the analysis of certified reference
      materials, CRM 545, Mess-3 and Pacs-2 with good agreement between certified and
      found values. Cr concentrations in air samples taken around the chromium smelter
      show concentrations that exceed the maximum allowed levels in 8h with higher
      values closer to the smelter. The limit of detection (LOD) of the method for
      Cr(VI) determination in air samples was found to be 0.2 ng m(-3), i.e. lower than
      offered by the commonly preferred spectrophotometric and colorimetric techniques.

PMID- 16442217
TI  - Model of large pool fires.
AB  - A two zone entrainment model of pool fires is proposed to depict the fluid flow
      and flame properties of the fire. Consisting of combustion and plume zones, it
      provides a consistent scheme for developing non-dimensional scaling parameters
      for correlating and extrapolating pool fire visible flame length, flame tilt,
      surface emissive power, and fuel evaporation rate. The model is extended to
      include grey gas thermal radiation from soot particles in the flame zone,
      accounting for emission and absorption in both optically thin and thick regions.
      A model of convective heat transfer from the combustion zone to the liquid fuel
      pool, and from a water substrate to cryogenic fuel pools spreading on water,
      provides evaporation rates for both adiabatic and non-adiabatic fires. The model
      is tested against field measurements of large scale pool fires, principally of
      LNG, and is generally in agreement with experimental values of all variables.

PMID- 16442218
TI  - Lidar characterization of crystalline silica generation and transport from a sand
      and gravel plant.
AB  - Light detection and ranging (Lidar) remote sensing two-dimensional vertical and
      horizontal scans collected downwind of a sand and gravel plant were used to
      evaluate the generation and transport of geologic fugitive dust emitted by quarry
      operations. The lidar data give unsurpassed spatial resolution of the emitted
      dust, but lack quantitative particulate matter (PM) mass concentration data.
      Estimates of the airborne PM10 and crystalline silica concentrations were
      determined using linear relationships between point monitor PM10 and quartz
      content data with the lidar backscatter signal collected from the point monitor
      location. Lidar vertical profiles at different distances downwind from the plant
      were used to quantify the PM10 and quartz horizontal fluxes at 2-m vertical
      resolution as well as off-site emission factors. Emission factors on the order of
      65-110 kg of PM10 (10-30 kg quartz) per daily truck activity or 2-4 kg/t product
      shipped (0.5-1 kg quartz/t) were quantified for this facility. The lidar results
      identify numerous elevated plumes at heights >30 m and maximum plume heights of
      100 m that cannot be practically sampled by conventional point sampler arrays.
      The PM10 and quartz mass flux was greatest at 10-25 m height and decreased with
      distance from the main operation. Measures of facility activity were useful for
      explaining differences in mass flux and emission rates between days. The study
      results highlight the capabilities of lidar remote sensing for determining the
      spatial distribution of fugitive dust emitted by area sources with intermittent
      and spatially diverse dust generation rates.

PMID- 16442219
TI  - Membrane based strategies for the pre-treatment of acid dye bath wastewaters.
AB  - This paper, as part of a study carried out for the recovery of the acid dye bath
      wastewaters of a carpet manufacturing industry by membrane processes, describes
      the evaluation of alternative strategies for the pre-treatment of acid dye bath
      wastewaters. Dead-end microfiltration (MF) simulating sand filtration with MF
      media having pore sizes of 2.5, 1.0, 0.45 and 0.2 microm and ultrafiltration (UF)
      with an UF membrane having a molecular weight cut off (MWCO) of 50,000 Da were
      tested in single and sequential stages in order to achieve the best treatment
      efficiency. Four alternative process trains were tested; single MF, sequential
      MF, single UF, and MF followed by UF. For both MF and UF, application of
      sequential filtration did not provide any significant benefit over single
      processes. In addition, chemical oxygen demand (COD) removal performance of all
      the alternative processes was similar where the highest removal was only 5%. On
      the other hand, color removals were much better; ranging from 15 to 100%, even
      with single MF. Comparison of all the process alternatives revealed that, single
      MF (0.45 microm), as the simplest process, is the most suitable pre-treatment
      method for the acid dye bath wastewaters.

PMID- 16442220
TI  - Biological treatment of para-chlorophenol containing synthetic wastewater using
      rotating brush biofilm reactor.
AB  - A novel rotating brush biofilm reactor (RBBR) was used for para-chlorophenol (4
      chlorophenol, 4-CP), COD and toxicity removal from synthetic wastewater
      containing different concentrations of 4-CP. Effects of major operating variables
      such as the feed 4-CP and COD concentrations and A/Q (biofilm surface area/feed
      flow rate) ratio on the performance of the biofilm reactor were investigated. A
      Box-Wilson statistical experiment design method was used by considering the feed
      4-CP (0-1000 mg l(-1)), COD (2000-6000 mg l(-1)) and A/Q ratio (73-293 m(2) day
      m(-3)) as the independent variables while the 4-CP, COD and toxicity removals
      were the objective functions. The results were correlated by a response function
      and the coefficients were determined by regression analysis. Percent 4-CP, COD
      and toxicity removals determined from the response functions were in good
      agreement with the experimental results. 4-CP, COD and toxicity removals
      increased with decreasing feed 4-CP and increasing A/Q ratio. Optimum conditions
      resulting in maximum COD, 4-CP and toxicity removals were found to be A/Q ratio
      of nearly 180 m(2) day m(-3), feed COD of nearly 4000 mg l(-1) and feed 4-CP of
      less than 205 mg l(-1).

PMID- 16442221
TI  - Applicability of the various adsorption models of three dyes adsorption onto
      activated carbon prepared waste apricot.
AB  - In this study, activated carbon (WA11Zn5) was prepared from waste apricot, which
      is waste in apricot plants in Malatya, by chemical activation with ZnCl(2). BET
      surface area of activated carbon is determined as 1060 m(2)/g. Activated carbon
      includes both micro and mesopores. Percentages of micropores and mesopores area
      are determined 36% and 74%, percentage of micropores and mesopores volume is 19%
      and 81%, respectively. The ability of WA11Zn5, to remove three dyes, methylene
      blue (MB), malachite green (MG), and crystal violet (CV), from effluent solutions
      by adsorption has been studied. The adsorption capacities of WA11Zn5 decreases in
      the order malachite green (MG)>methylene blue (MB)>crystal violet (CV).
      Equilibrium isotherms for the adsorption of three dyes on activated carbon were
      measured experimentally. Results were analyzed by the Langmiur, Freundlich,
      Dubinin-Redushkevich (D-R), Temkin, Frumkin, Harkins-Jura, Halsey and Henderson
      equation using linearized correlation coefficient at different temperature. The
      characteristic parameters for each isotherm have been determined. Models and the
      isotherm constant were evaluated depending on temperature. Langmiur and Frumkin
      equation is found to best represent the equilibrium data for three dye-WA11Zn5
      systems.

PMID- 16442222
TI  - Simultaneous removal of SO2 and NO by wet scrubbing using aqueous chlorine
      dioxide solution.
AB  - The present study attempts to generate chlorine dioxide (ClO(2)) gas continuously
      by chlorate-chloride process and to utilize it further to clean up SO(2) and
      NO(x) gases simultaneously from the flue gas in the lab-scale bubbling reactor.
      Experiments were carried out to examine the effect of various operating
      parameters like input SO(2) concentration, input NO concentration, pH of the
      reaction medium, and ClO(2) feeding rate on the SO(2) and NO(x) removal
      efficiencies at 45 degrees C. Complete oxidation of NO into NO(2) occurred on
      passing sufficient ClO(2) gas into the scrubbing solution. SO(2) removal
      efficiency of about 100% and NO(x) removal efficiency of 66-72% were achieved
      under optimized conditions. NO(x) removal efficiency decreased slightly with
      increasing pH and NO concentration. Input SO(2) concentration had marginal
      catalytic effect on NO(2) absorption. No improvement in the NO(x) removal
      efficiency was observed on passing excess of chlorine dioxide in the scrubbing
      solution.

PMID- 16442223
TI  - Hydrometallurgical processing of carbon steel EAF dust.
AB  - In this study, the hydrometallurgical processing of electric arc furnace (EAF)
      steelmaking dust is investigated on a laboratory scale under normal temperature
      and pressure conditions. The behaviour of zinc and iron under the influence of
      sulphuric acid as the leaching agent is discussed. The dependence between the
      temperature and acid concentration is investigated. The main aim is the transfer
      of zinc into the solution while iron ought to remain as a solid residue. The
      hydrometallurgical recovery of zinc from EAF dust is feasible with relatively
      high recovery yield, while iron mostly remains in the solid phase. It results
      from the use of sulphuric acid in low concentration. This way, it is possible to
      set up the conditions for the EAF dust leaching, adjusting sulphuric acid
      concentration in order to achieve an optimum zinc yield to the solution without
      iron dissolution. However, the problem is that the chemical and mineralogical
      composition of each steelmaking dust is individual.

PMID- 16442224
TI  - Adsorption of aromatic organic acids onto high area activated carbon cloth in
      relation to wastewater purification.
AB  - Adsorption of aromatic organic acids: benzoic acid (BA), salicylic acid (SA), p
      aminobenzoic acid (pABA) and nicotinic acid (NA), onto high area activated carbon
      cloth from solutions in 0.4 M H(2)SO(4), in water at natural pH, in 0.1 M NaOH
      and also from solutions having pH 7.0 were studied by in situ UV-spectroscopic
      technique. The first-order rate law was found to be applicable for the kinetic
      data of adsorption. The rates and extents of adsorption of the organic acids were
      the highest from water or 0.4 M H(2)SO(4) solutions and the lowest from 0.1 M
      NaOH solution. The order of rates and extents of adsorption of the four organic
      acids in each of the four solutions (0.4 M H(2)SO(4), water, solution of pH 7.0
      and 0.1 M NaOH) was determined as SA>BA>NA approximately pABA. These observed
      orders were explained in terms of electrostatic, dispersion and hydrogen bonding
      interactions between the surface and the adsorbate species, taking the charge of
      the carbon surface and the adsorbate in each solution into account. Adsorption of
      BA in molecular form or in benzoate form was analyzed by treating the solution as
      a mixture of two components and applying Lambert-Beer law to two-component
      system. The adsorption isotherm data of the systems studied were derived at 30
      degrees C and fitted to Langmuir and Freundlich equations.

PMID- 16442225
TI  - The criteria of critical runaway and stable temperatures of catalytic
      decomposition of hydrogen peroxide in the presence of hydrochloric acid.
AB  - The hydrogen peroxide and hydrochloric acid are used in close proximity in the
      computer chip manufacture. The hydrochloric acid catalyzes an exothermic
      decomposition of hydrogen peroxide into oxygen and water. The accumulation of
      heat and non-condensable gas increases temperature and pressure in this reaction
      process always lead to runaway reaction and accident owing to inadvertent mixing.
      Thus, the chemical reaction hazard has to be clearly identified. Its critical
      runaway temperatures and unstable reaction criteria in this reaction process have
      to be determined urgently. In this investigation, we estimated its kinetic
      parameters at various volumetric ratios of the hydrogen peroxide to hydrochloric
      acid. Then, used these kinetic parameters to evaluate their critical temperatures
      and stable criteria in each reaction processes. The analytic results are
      important and useful for the design of safety system in the computer chip
      manufacture.

PMID- 16442226
TI  - Seasonal variations of lead concentration and loading rates in residential house
      dust in northern Idaho.
AB  - Although lead hazards to humans have been known since ancient times and many
      regulatory actions and lead risk reductions have been achieved over the past
      century, lead contamination and exposure remain significant problems worldwide.
      The focus of this study was to investigate whether residential house dust lead
      concentrations and lead and dust loading rates in non-contaminated or
      "background" communities in northern Idaho are significantly affected by seasonal
      variations. House dust samples were obtained from 34 houses in five towns of
      northern Idaho from March to November 1999. There was evidence of significant
      seasonality of lead concentration in house dust in some towns, but no evidence in
      other towns. Because of the high variability between the towns and small sample
      sizes, it was difficult to make firm conclusions about seasonal patterns observed
      in house dust lead levels. A linear relationship between precipitation rates and
      dust loading rates was detected.

PMID- 16442227
TI  - Adsorption characteristics of heavy metal ions onto a low cost biopolymeric
      sorbent from aqueous solutions.
AB  - In this study, the adsorption conditions of Cu(II), Pb(II) and Cd(II) metal ions
      onto sporopollenin have been studied. The different variables effecting the
      sorption capacity such as pH of the solution, adsorption time, initial metal ion
      concentration and temperature have been investigated. Adsorption isotherms
      correlated well with the Freundlich type adsorption isotherm and adsorption
      capacities were found to be 0.0195, 0.0411 and 0.0146 mmol g(-1) for Cu(II),
      Pb(II) and Cd(II) metal ions, respectively. Experimental data were also evaluated
      to find out kinetic characteristics of the adsorption process. Adsorption
      processes for three target heavy metal ions were found to follow pseudo-second
      order type adsorption kinetics. Intraparticle diffusion was found to take part in
      adsorption processes but it could not be accepted as the primary rate-determining
      step. The mean free energies of adsorption (E) were found to be between 8 and 16
      kJ mol(-1) for the metal ions studied and therefore adsorption mechanism for the
      adsorbent was explained as an ion-exchange process. But it was observed that
      chelating effect is also playing an important role in the adsorption of metal
      ions onto sporopollenin. Thermodynamic parameters, DeltaH degrees , DeltaS
      degrees and DeltaG degrees were also calculated from graphical interpretation of
      the experimental data. Standard heats of adsorption (DeltaH degrees ) were found
      to be endothermic and DeltaS degrees values were calculated to be positive for
      the adsorption of Cu(II), Pb(II) and Cd(II) ions onto the adsorbent. Negative
      DeltaG degrees values indicated that adsorption process for these three metal
      ions onto sporopollenin is spontaneous.

PMID- 16442228
TI  - Kinetics and thermodynamics of adsorption of azinphosmethyl from aqueous solution
      onto pyrolyzed (at 600 degrees C) ocean peat moss (Sphagnum sp.).
AB  - The removal of azinphosmethyl from aqueous solution onto pyrolyzed ocean peat
      moss (Sphagnum sp.), as a residue, from the Rhode Island coast (USA), has been
      investigated at different temperatures and initial concentrations. The ocean peat
      moss had been pyrolyzed at 600 degrees C in nitrogen atmosphere before the
      adsorption process. The kinetic data obtained from batch studies have been
      analyzed using pseudo-first order kinetic model. The rate constants were
      evaluated at different temperatures. The thermodynamic parameters (DeltaG degrees
      , DeltaH degrees , DeltaS degrees ) for the adsorption process were calculated
      and the results suggest that the nature of adsorption is endothermic and the
      process is spontaneous and favorable. The activation energy for adsorption
      process was estimated, about 18.3 kJ mol(-1). According to this value the
      adsorption of azinphosmethyl onto pyrolyzed ocean peat moss is in the range of
      physical adsorption. The experimental data have been modeled using Langmuir,
      Freundlich and Temkin isotherms. It was found that Langmuir and Freundlich
      isotherms give the best correlation with the experimental data.

PMID- 16442229
TI  - Evaluation of PCDD/Fs emission from fluidized bed incinerators co-firing MSW with
      coal in China.
AB  - The levels and homologue profile of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) from stack gas of three typical fluidized bed
      incinerators co-firing municipal solid waste (MSW) with Chinese coal were
      measured. The PCDD/Fs emission was in the range of 0.0054-0.1961 ng I-TEQ/N m(3).
      Comparison of PCDD/Fs detection results by HRGC/HRMS and HRGC/LRMS suggested that
      it was feasible to detect fly ash with high PCDD/Fs concentration by HRGC/LRMS.
      Several factors on PCDD/Fs emission were discussed. The primary reason for the
      lower PCDD/Fs emission was the inhibition mechanism of relatively high sulfur in
      feeding coal on PCDD/Fs formation. The emission results also showed that there
      was no directly correlation between PCDD/Fs levels and CO, O(2) and HCl
      concentration in flue gas. It was estimated that about 0.1034 g I-TEQ was
      annually emitted to atmosphere from the tested three MSW incinerators (total
      daily treatment capacity is 800 tonnes MSW).

PMID- 16442230
TI  - Characterization of the nuclear targeting signal of REST/NRSF.
AB  - RE-1 silencer transcription factor (REST), also known as neuron-restrictive
      silencer factor (NRSF), contains nine Cys2-His2 type zinc finger domains (ZFDs).
      REST/NRSF is localized to the nucleus, where it represses the transcriptional
      activity of a large number of neuronal genes in non-neuronal cells. It has been
      suggested that REST/NRSF contains a nuclear localization signal (NLS)
      corresponding to amino acids (512-522). However, our studies showed that REST4, a
      REST/NRSF splicing isoform, which contains the N-terminal 5 of 9 ZFDs,
      efficiently localized to the nucleus. On the other hand REST1, another REST/NRSF
      splicing isoform, which contains 4 of the 9 ZFDs, localized to the cytosol. In
      this study REST-DeltaC, which contains 8 ZFDs with the NLS (512-522) deleted, was
      found to localize to the nucleus in HeLa, COS and PC12 cells. Complete deletion
      or mutation of NLS (512-522) still permitted REST/NRSF to be localized to the
      nucleus in HeLa, COS and PC12 cells. In contrast REST/NRSF constructs which
      contain a deletion of ZFD-5 mislocalized to the cytosol. A point mutation in the
      zinc finger structure that disrupts its conformation remains nuclear. These data
      suggest that REST/NRSF contains a NLS around ZFD-5, while the putative NLS at
      residues 512-522 is non-functional.

PMID- 16442231
TI  - Detection of lipid peroxidation in light-exposed mouse retina assessed by
      oxidative stress markers, total hydroxyoctadecadienoic acid and 8-iso
      prostaglandin F2alpha.
AB  - Exposure to excessive light induces retinal photoreceptor cell damage, which may
      involve lipid peroxidation. Morphological changes and the detection of
      internucleosomal DNA fragmentation confirmed the retinal damage caused by
      exposure of the retina of Balb/c mice to white fluorescent light (5000 lux, 2 h).
      The total amounts of hydroxyoctadecadienoic acid (tHODE) and 8-iso-prostaglandin
      F2alpha (8-iso-PGF2alpha) in the retinas obtained from light-exposed mice were
      assessed after reduction and saponification. In this method, both the free and
      ester forms of hydroperoxides, hydroxides, and ketones of linoleic acid are
      measured as tHODE by gas chromatography-mass spectrometry (GC-MS) analysis. When
      compared with controls, a significant increase in the concentrations of tHODE and
      8-iso-PGF2alpha was observed 24 h after light exposure. Furthermore, the
      stereoisomeric ratio (Z,E)-HODE/(E,E)-HODE decreased after light exposure,
      suggesting the involvement of free-radical-mediated peroxidation. By the
      immunohistochemical technique, it was confirmed that 8-iso-PGF2alpha increased in
      the inner plexiform layer (IPL), outer plexiform layer (OPL), rod outer segment,
      and choroidal layer, while 13-HODE increased in the OPL and rod inner segment
      after light exposure. These results demonstrate that tHODE and 8-iso-PGF2alpha
      assessed by the present method are appropriate biomarkers responding to retinal
      photooxidative stress in vivo.

PMID- 16442232
TI  - ACE gene polymorphisms influence t-PA-induced brain vessel reopening following
      ischemic stroke.
AB  - Angiotensin converting enzyme (ACE) influences vessels tone and the
      coagulation/fibrinolysis system. The ACE gene I/D polymorphism has been linked
      with PAI-1 and fibrinogen levels and with Factors VII and X activities.
      Therefore, we aimed to test whether I/D polymorphism could be related to
      thrombolysis safety and efficacy. We studied strokes involving the middle
      cerebral artery (MCA) territory of patients who received t-PA <3 h of stroke
      onset. Blood samples were obtained before t-PA administration to measure
      fibrinogen, PAI-1, Factors VII and X. I/D polymorphism was determined by
      polymerase chain reaction and agarose electrophoresis. Recanalization rates were
      serially evaluated by Transcranial Doppler. Among 96 included patients the
      genotype frequency was: DD=33.3%, ID=57.3% and II=9.4%. A strong association was
      found between DD homozygous and successful recanalization rates (DD=69.2%,
      ID+II=31.6%, p=0.002 at 1 h; DD=91.3%, ID+II=51%, p=0.001 at 6 h; DD=100%,
      ID+II=72.3%, p=0.003 at 24 h post-t-PA administration). In fact, DD genotype was
      an independent predictor of recanalization (OR=4.3 95% CI 1.35-13.49, p=0.013).
      No relation was found between I/D polymorphism and symptomatic hemorrhagic
      complications (p=0.237). No association between ACE genotypes and Factor VII or
      Factor X activities, neither with fibrinogen or PAI-1 levels was observed. DD
      homozygous is strongly associated with MCA recanalization following t-PA
      treatment. Mechanisms of benefit remain unknown since I/D polymorphism had
      similar FVII and X activities and PAI-1 and fibrinogen levels in our stroke
      population.

PMID- 16442233
TI  - Qualitative and quantitative observations on the flea population dynamics of dogs
      and cats in several areas of Germany.
AB  - From an ongoing country-wide study on the spectrum, the epidemiology and the
      population dynamics of flea infestations in dogs and cats, important preliminary
      results from the three areas of Karlsruhe, Nuernberg and Leipzig are presented. A
      total of 1922 dogs and 1838 cats from 12 different veterinary practices or
      clinics in three areas of Germany were systematically examined between July 2003
      and June 2004. All dogs and cats appearing for a clinical veterinary consultation
      on one regular working day per month, per practice, were clinically examined.
      Dogs and cats were examined irrespective of any kind of prior therapeutic or
      prophylactic insecticidal treatment. The results show that a total of 99 dogs
      (5.13%) and 263 cats (14.33%) were infested. Cats were more often flea-infested
      than dogs (p < 0.05). The highest infestation rates for dogs (x = 7.87%) were
      detected between July and October, and for cats (x = 21.14%) between July and
      September, the lowest infestation rates for dogs (x = 2.88%) were observed
      between November and May, and for cats (x = 12.16%) between November and April (p
      < 0.05). Although the prevalences were generally higher during the summer months,
      no statistical differences were detectable when looking at the pattern between
      the four seasons, neither for dogs, nor for cats. Interestingly, the highest
      prevalences in dogs (9.9%) were detected in June 2004 and comparatively, in cats
      (23.86%) in August. The lowest detection rates in dogs were seen (1.28%) in April
      and in cats (7.26%) in January. The preliminary results did not indicate any
      tendency for a relationship between climatic conditions and flea infestation
      rates. Similarly, no differences of the infestations rates were detectable
      between urban and rural areas, 56% (dogs) and 46% (cats) of the infested pets
      originated from urban habitats. The flea species collected include
      Ctenocephalides felis, Ctenocephalides canis, Archaeopsylla erinacei, Pulex
      irritans, Ceratophyllus gallinae, etc. The overall frequencies reveal that C.
      felis was the most prominent species (81.5%), followed by C. canis (12.5%), A.
      erinacei (2.7%) and P. irritans (1.7%).

PMID- 16442234
TI  - Increased blood plasma hydrolysis of acetylsalicylic acid in type 2 diabetic
      patients: a role of plasma esterases.
AB  - Hydrolysis of acetylsalicylic acid (ASA, aspirin), an antiplatelet drug commonly
      used in the prevention of stroke and myocardial infarction, seems to play a
      crucial role in its pharmacological action. Thirty-eight healthy volunteers and
      38 type 2 diabetic patients were enrolled to test the hypothesis that the
      enhanced plasma degradation and lowered bioavailability of ASA in diabetic
      patients is associated with the attenuation of platelet response. Aspirin
      esterase activities were tested at pH 7.4 and 5.5. A significantly higher overall
      aspirin esterase activity was noted at pH 7.4 in the diabetic patients (P<0.003),
      corresponding to faster ASA hydrolysis (P<0.006). This increased activity was
      attributable to butyrylcholinesterase and probably to albumin, because it was
      effectively inhibited by eserine and 4-bis-nitrophenyl phosphate (P<0.01). No
      significant differences between control and diabetic subjects were found at pH
      5.5 in either enzymatic activities or ASA hydrolysis rates. The enhanced plasma
      ASA degradation in diabetic subjects was significantly associated with the
      refractoriness of blood platelets to ASA (P<0.05) and modulated by plasma
      cholesterol (P<0.01). No direct effects of plasma pH or albumin were observed. In
      conclusion, higher aspirin esterase activity contributes to the lowered response
      of diabetic platelets to ASA-mediated antiplatelet therapy.

PMID- 16442235
TI  - Ovotransferrin is a redox-dependent autoprocessing protein incorporating four
      consensus self-cleaving motifs flanking the two kringles.
AB  - Embryos of avian eggs and mammals are highly sensitive to oxidative stress and
      hence maintaining a steady reducing environment during the embryonic development
      is known to confer protection. Although information is completely lacking,
      proteins of avian egg albumin which have been suggested to play various
      biological functions, are the major targets for such reducing state during
      embryogenesis. In this study, we found that ovotransferrin (OTf), the second
      major protein in egg albumin, undergoes autocleavage at distinct sites upon
      reduction with thiol-reducing agent or thioredoxin-reducing system. Mass spectral
      and microsequencing analysis indicated that OTf is able to cleave itself through
      the unique chemical reactivity of four tripeptides motifs, HTT (residues 209
      211), HST (residues 542-544) and two CHT (residues 115-117 and 454-456).
      Intriguingly, these self-cleavage sites were uniquely located upstream and
      downstream of the two disulfide kringle domains (residues 115-211 and 454-544) of
      OTf. These reduction-scissile sequences, His/Cys-X-Thr, are evolutionary
      conserved self-cleavage motifs found in several autoprocessing proteins including
      hedgehog proteins. Interestingly, reduction of other two members of transferrin
      family induced autocleavage patterns, similar to that of OTf, in bovine
      lactoferrin (bLf) while human lactoferrin (hLf) showed much less self-cleaving
      activity. This finding is the first to describe that transferrins are a new
      subset in the class of proteins able to carry out autoprocessing, providing
      insight into this unusual biochemical process that appears to be a molecular
      switch involved in triggering a yet unidentified function(s) of OTf as well as
      bLf.

PMID- 16442236
TI  - Extracellular signal-regulated kinase as an inducer of non-apoptotic neuronal
      death.
AB  - Extracellular signal-regulated kinase (ERK) is a versatile protein kinase, which
      has been implicated in signaling numerous biological functions ranging from
      embryonic development to memory formation. Recent reports, including ours,
      indicate that ERK plays a central role in promoting neuronal degeneration in
      various neuronal systems including neurodegenerative diseases. Mechanisms
      involved in ERK-induced neuronal degeneration are beginning to emerge. In this
      review, we summarize evidence suggesting ERK to be a predominant inducer of a non
      apoptotic mode of neuronal death. Further, we discuss the mechanisms and the
      putative molecular inter-players associated with ERK-mediated neuronal death.

PMID- 16442238
TI  - Intensity-modulated radiotherapy for the treatment of vulvar carcinoma: a
      comparative dosimetric study with early clinical outcome.
AB  - OBJECTIVES: To assess early clinical outcome of intensity-modulated radiation
      therapy (IMRT) in the treatment of vulvar cancer and compare dosimetric
      parameters with 3D conformal radiotherapy (3D CRT). METHODS: Fifteen patients
      with vulvar cancer were treated with IMRT. Seven patients were treated with
      preoperative chemoradiation, and 8 patients were treated with adjuvant
      postoperative radiation therapy. Median dose was 46 Gy in the preoperative and
      50.4 Gy in the postoperative group. RESULTS: The mean volume of small bowel,
      rectum, and bladder that received doses in excess of 30 Gy with IMRT was reduced
      when compared with 3D CRT. Treatment was well tolerated, and only 1 patient had
      acute Grade 3 small-bowel toxicity. Median follow-up was 12 months. In the
      preoperative group, 5 patients (71%) had clinical complete response and 3
      patients (42.8%) had pathologic complete response. In the adjuvant group, 2
      patients had recurrences in the treatment field. No patients had late Grade 3
      toxicity. The 2-year actuarial disease-specific survival was 100%. CONCLUSIONS:
      Intensity-modulated RT appears to offer advantages over 3D CRT treatment of
      vulvar cancer by elimination of dose modulation across overlapping regions and
      reduction of unnecessary dose to the bladder, rectum, and small bowel. Early
      results with a small number of patients show promising results, with a low
      incidence of severe toxicity.

PMID- 16442239
TI  - Feasibility of a novel deformable image registration technique to facilitate
      classification, targeting, and monitoring of tumor and normal tissue.
AB  - PURPOSE: To investigate the feasibility of a biomechanical-based deformable image
      registration technique for the integration of multimodality imaging, image guided
      treatment, and response monitoring. METHODS AND MATERIALS: A multiorgan
      deformable image registration technique based on finite element modeling (FEM)
      and surface projection alignment of selected regions of interest with
      biomechanical material and interface models has been developed. FEM also provides
      an inherent method for direct tracking specified regions through treatment and
      follow-up. RESULTS: The technique was demonstrated on 5 liver cancer patients.
      Differences of up to 1 cm of motion were seen between the diaphragm and the tumor
      center of mass after deformable image registration of exhale and inhale CT scans.
      Spatial differences of 5 mm or more were observed for up to 86% of the surface of
      the defined tumor after deformable image registration of the computed tomography
      (CT) and magnetic resonance images. Up to 6.8 mm of motion was observed for the
      tumor after deformable image registration of the CT and cone-beam CT scan after
      rigid registration of the liver. Deformable registration of the CT to the follow
      up CT allowed a more accurate assessment of tumor response. CONCLUSIONS: This
      biomechanical-based deformable image registration technique incorporates
      classification, targeting, and monitoring of tumor and normal tissue using one
      methodology.

PMID- 16442237
TI  - TNFR1 mediates increased neuronal membrane EAAT3 expression after in vivo
      cerebral ischemic preconditioning.
AB  - A short ischemic event (ischemic preconditioning) can result in subsequent
      resistance to severe ischemic injury (ischemic tolerance). Glutamate is released
      after ischemia and produces cell death. It has been described that after ischemic
      preconditioning, the release of glutamate is reduced. We have shown that an in
      vitro model of ischemic preconditioning produces upregulation of glutamate
      transporters which mediates brain tolerance. We have now decided to investigate
      whether ischemic preconditioning-induced glutamate transporter upregulation takes
      also place in vivo, its cellular localization and the mechanisms by which this
      upregulation is controlled. A period of 10 min of temporary middle cerebral
      artery occlusion was used as a model of ischemic preconditioning in rat. EAAT1,
      EAAT2 and EAAT3 glutamate transporters were found in brain from control animals.
      Ischemic preconditioning produced an up-regulation of EAAT2 and EAAT3 but not of
      EAAT1 expression. Ischemic preconditioning-induced increase in EAAT3 expression
      was reduced by the TNF-alpha converting enzyme inhibitor BB1101. Intracerebral
      administration of either anti-TNF-alpha antibody or of a TNFR1 antisense
      oligodeoxynucleotide also inhibited ischemic preconditioning-induced EAAT3 up
      regulation. Immunohistochemical studies suggest that, whereas the expression of
      EAAT3 is located in both neuronal cytoplasm and plasma membrane, ischemic
      preconditioning-induced up-regulation of EAAT3 is mainly localized at the plasma
      membrane level. In summary, these results demonstrate that in vivo ischemic
      preconditioning increases the expression of EAAT2 and EAAT3 glutamate
      transporters the upregulation of the latter being at least partly mediated by TNF
      alpha converting enzyme/TNF-alpha/TNFR1 pathway.

PMID- 16442240
TI  - Time trends in target volumes for stage I non-small-cell lung cancer after
      stereotactic radiotherapy.
AB  - PURPOSE: To identify potential time trends in target volumes and tumor mobility
      after stereotactic radiotherapy (SRT) for Stage I non-small-cell lung cancer.
      PATIENTS AND METHODS: Repeat planning computed tomography (CT) scans were
      performed for 40 tumors during fractionated SRT delivered in either three (n =
      21), five (n = 14), or eight fractions (n = 5). The planning CT scans used to
      define internal target volumes (ITVs) consisted of either six multislice CT scans
      or a single four-dimensional CT scan. All repeat CT scans were coregistered with
      the initial (D0) scan to determine volumetric or spatial changes in target
      volume, and tumor mobility vectors were determined from each scan. RESULTS: A
      significant decrease in target volumes (ITVs and gross tumor volumes) relative to
      baseline values was observed starting at the fourth week of SRT (p = 0.015). No
      trends in tumor mobility were detected during SRT. Significant positional shifts
      in the ITV, of more than 5 mm, were seen in 26-43% of patients at different times
      during SRT. CONCLUSION: Significant changes in target volumes can occur during
      SRT for Stage I non-small-cell lung cancer. A failure to account for such changes
      e.g., by repeat CT planning or verification using on-board volumetric imaging can
      lead to inadequate target coverage.

PMID- 16442241
TI  - Intraoperative radiotherapy given as a boost for early breast cancer: long-term
      clinical and cosmetic results.
AB  - PURPOSE: The standard radiotherapy (RT) of breast cancer consists of 50 Gy
      external beam RT (EBRT) to the whole breast followed by an electron boost of 10
      16 Gy to the tumor bed, but this has several cosmetic disadvantages.
      Intraoperative radiotherapy (IORT) could be an alternative to overcome these.
      METHODS AND MATERIALS: We evaluated 50 women with early breast cancer operated on
      in a dedicated IORT facility. Median dose of 10 Gy was delivered using 9-MeV
      electron beams. All patients received postoperative EBRT (50 Gy in 2 Gy
      fractions). Late toxicity and cosmetic results were assessed independently by two
      physicians according to the Common Terminology Criteria for Adverse Event v3.0
      grading system and the European Organization for Research and Treatment of Cancer
      questionnaires. RESULTS: After a median follow-up of 9.1 years (range, 5-15
      years), two local recurrences were observed within the primary tumor bed. At the
      time of analysis, 45 patients are alive with (n = 1) or without disease. Among
      the 42 disease-free remaining patients, 6 experienced Grade 2 late subcutaneous
      fibrosis within the boost area. Overall, the scores indicated a very good quality
      of life and cosmesis was good to excellent in the evaluated patients. CONCLUSION:
      Our results confirm that IORT given as a boost after breast-conserving surgery is
      a reliable alternative to conventional postoperative fractionated boost
      radiation.

PMID- 16442242
TI  - [Use of multilocus sequence typing and pulsed-field gel electrophoresis for the
      study of serogroup B Neisseria meningitidis isolates from Casablanca (Morocco)].
AB  - A previous study showed that B:4:P1.15 was the most frequent phenotype of
      Neisseria meningitidis isolated in Casablanca (Morocco). To determine if there
      was an epidemic clone, MLST and PFGE were used to compare 13 B:4:P1.15 strains
      isolated from September 1999 to December 2000. MLST showed 4 Sequence Types (ST):
      ST-33 was the most frequent ST (9/13 strains) and 4 strains belonged to 3 newly
      described STs. Twelve stains belonged to ST-32 complex, and one strain presenting
      a new ST (ST-2502) did not belong to any known ST complex. The analysis by PFGE
      showed that the strains were subdivided into 7 clusters, and that there was no
      epidemic clone. MLST is useful for long-term epidemiological studies on N.
      meningitidis strains from varied geographical origins. PFGE seemed to be well
      adapted to the comparison of a small number of strains isolated during a short
      period within a defined community.

PMID- 16442243
TI  - Chromogranin-A expression in the bovine testis.
AB  - Chromogranin-A (CgA) is the most distributed member of the granin family.
      Chromogranins are soluble anionic glycoproteins, found in the majority of the
      neuroendocrine and neural cells, co-stored with other endocrine substances (like
      insulin, glucagon, FSH and LH or NPY) in secretory granules. Outside the cell, it
      has been suggested that this peptide or one of its fragments, obtained by
      proteolytic cleavage, could act in an autocrine or paracrine way, regulating
      either the cell function or the contractibility of vascular segments. The purpose
      of the present study is to determine the distribution of chromogranin-A in the
      structures of the bovine testis. Immunohistochemical analysis was performed
      employing the biotin-streptavidin-peroxidase immunostaining technique in tissue
      specimens obtained at a local abbatoir. A CgA expression was found in the
      germinal epithelium at several stages of differentiation. Generally the strongest
      positive reaction was consistently observed in the basal compartment of the
      seminiferous tubules, with spermatogonia presenting a dense granular
      immunostaining pattern; a less intense reaction was also consistently recorded in
      type II spermatocytes and in round spermatids, which showed a more scattered
      disposition of CgA-positive granules. Clusters of Leydig cells also displayed a
      faint and homogeneous cytoplasmatic immunoreactivity for chromogranin-A. These
      results demonstrate a widely distribution of CgA-positive cells in the organism,
      and its presence in the testis raises the possibility of its participation in the
      cohort of local factors involved in the regulation of spermatogenesis.

PMID- 16442244
TI  - A role for LH in the regulation of expression of mRNAs encoding components of the
      insulin-like growth factor (IGF) system in the ovine corpus luteum.
AB  - Evidence suggests the insulin-like growth factor (IGF) system may be involved in
      luteal maintenance and regression. However, previous studies have only
      investigated a few components of the system, primarily in bovine and non-ruminant
      species. The present study investigated gene expression for the components of the
      IGF system in ovine corpora lutea (CL) at various key stages of the oestrous
      cycle (Experiment 1), and the possible regulatory effects of LH on IGF gene
      expression in ovine CL using a GnRH antagonist model system (Experiment 2).
      Experiment 1 revealed that IGF-I (P<0.001), type I (P=0.008) and II (P=0.005) IGF
      Rs and IGFBP-5 (P<0.05) mRNA levels were significantly elevated in early
      regressing CL. In contrast, IGF-II levels were high in CL but did not vary
      throughout the oestrous cycle, while IGFBP-2, -3, -4 and -6 mRNA levels were
      highest throughout the luteal phase but lower in regressing CL (P<0.05). IGFBP-1
      mRNA could not be detected in any CL. Abrogation of LH action following GnRH
      antagonist administration (Experiment 2) resulted in a significant increase in
      expression for IGF-I (P<0.001), type II IGF-R (P=0.004) and IGFBP-5 (P<0.05)
      after only 12h, but these increases were transient. IGF-II, type I IGF-R and
      IGFBP-2, -3, -4 and -6 mRNA levels remained unaffected by GnRH antagonist
      treatment. These data highlight the role that LH plays in regulating IGF-I gene
      expression and lends further support that IGF-I may be a key luteotrophic factor
      in sheep.

PMID- 16442245
TI  - Intracellular uptake and release of poly(ethyleneimine)-co-poly(methyl
      methacrylate) nanoparticle/pDNA complexes for gene delivery.
AB  - Our previous studies demonstrated that cationic nanoparticles composed of well
      defined poly(methyl methacrylate) (PMMA) cores surrounded by a hairly
      poly(ethyleneimine) (PEI) shells have comparative advantages over the PEI system
      for gene delivery. In this study, we focused on the intracellular uptake and
      release of PEI-PMMA nanoparticle/pDNA complexes. The behavior of the
      nanoparticle/pDNA complexes in recipient cells was monitored by using confocal
      laser scanning microscopy. We found that the nanoparticle/pDNA complexes were
      internalized very effectively by endocytosis. In the recipient cells the
      nanoparticles were found localized in the cytoplasm. At the same time, the pDNA
      carried by the nanoparticles successfully detached from the nanoparticles and
      localized in the nucleus of the HeLa cells.

PMID- 16442246
TI  - Air classifier technology (ACT) in dry powder inhalation Part 4. Performance of
      air classifier technology in the Novolizer multi-dose dry powder inhaler.
AB  - In this study, the in vitro fine particle deposition from a multi dose dry powder
      inhaler (Novolizer) with air classifier technology has been investigated. It is
      shown that different target values for the fine particle fraction (fpf<5 microm)
      of the same drug can be achieved in a well-controlled way. This is particularly
      relevant to the application of generic formulations in the inhaler. The well
      controlled and predictable fpf is achieved through dispersion of different types
      of formulations in exactly the same classifier concept. On the other hand, it is
      shown that air classifier-based inhalers are less sensitive to the carrier
      surface and bulk properties than competitive inhalers like the Diskus. For 10
      randomly selected lactose carriers for inhalation from four different suppliers,
      the budesonide fpf (at 4 kPa) from the Novolizer varied between 30 and 46% (of
      the measured dose; R.S.D.=14.2%), whereas the extremes in fpf from the Diskus dpi
      were 7 and 44% (R.S.D.=56.2%) for the same formulations. The fpf from a
      classifier-based inhaler appears to be less dependent of the amount of lactose
      (carrier) fines (<15 microm) in the mixture too. Classifier-based inhalers
      perform best with coarse carriers that have relatively wide size distributions
      (e.g. 50-350 microm) and surface discontinuities inside which drug particles can
      find shelter from press-on forces during mixing. Coarse carrier fractions have
      good flow properties, which increases the dose measuring accuracy and
      reproducibility. The fpf from the Novolizer increases with increasing pressure
      drop across the device. On theoretical grounds, it can be argued that this yields
      a more reproducible therapy, because it compensates for a shift in deposition to
      larger airways when the flow rate is increased. Support for this reasoning based
      on lung deposition modelling studies has been found in a scintigraphic study with
      the Novolizer. Finally, it is shown that this inhaler produces a finer aerosol
      than competitor devices, within the fpf<5 microm, subfractions of particles (e.g.
      <1, 1-2, 2-3, 3-4 and 4-5 microm) are higher.

PMID- 16442247
TI  - Antimycotic influence of beta-cyclodextrin complexes--in vitro measurements using
      laser nephelometry in microtiter plates.
AB  - To determine the in vitro susceptibility of fungal organisms to beta-cyclodextrin
      (CD) complexes with the antifungal agents econazole-nitrate (EC) and ciclopirox
      olamine (CI), a fast, rapid and simple method using laser nephelometry in 96
      microtiter plate is used. The antimycotic influence of the complexes against
      Candida albicans DSM 11225 and Candida krusei ATCC 6258 species was determined
      using this method. A rapid inhibition and even killing of both fungi was observed
      only above certain concentrations of complex ranged between 12.5 and 100
      microg/ml for beta-CD-econazole complex (CD-EC), while for the complex with
      ciclopirox-olamine (CD-CI) the range was between 150 and 400 microg/ml. The
      stability constants of the CD complexes with the two antimycotic derivatives are
      given. In addition, the nephelometric method allows the determination of
      solubilities of active agents. Thus, the improvement of solubility of both
      antimycotic agents in PBS buffer solution was observed by complexation with CD.

PMID- 16442249
TI  - The cochlear implant electrode-pitch function.
AB  - The cochlear frequency-place function in normal hearing ears has been found to be
      an exponential relationship in a wide variety of species [D.D. Greenwood, J.
      Acoust. Soc. Am. 87 (1990) 2592-2605]. Although it seems reasonable to assume a
      similar function for electrical stimulation by means of an intra-cochlear
      electrode array, the exact frequency-place function for this special type of
      stimulation needs to be investigated. Six users of the MED-EL COMBI 40+ cochlear
      implant device with moderate to profound hearing loss between 125 and 1000 Hz in
      the non-implanted ear took part in a binaural pitch adjustment experiment. The
      COMBI 40+ electrode array provides a deep insertion into the scala tympani and a
      wide spatial separation between the stimulating electrodes. Insertion depth was
      controlled by Stenver's view plain radiographs and the insertion angle was
      estimated. The task of the subjects was to adjust the frequency of a sinusoid
      presented in the non-implanted ear by means of an adjusting knob until they
      perceived the same pitch as was elicited by a reference stimulus in the implanted
      ear. The results show adjustments corresponding to electrode positions along the
      cochlea, with the exception of the two most apical electrodes for most of the
      subjects. Pitch increased in an orderly fashion with an average of 98 Hz per
      electrode separation (40 Hz/mm). In contrast to the exponential predictions
      according to [D.D. Greenwood, J. Acoust. Soc. Am. 87 (1990) 2592-2605] for normal
      hearing, the average electrode-pitch function shows a linear relationship.

PMID- 16442248
TI  - Air classifier technology (ACT) in dry powder inhalation Part 3. Design and
      development of an air classifier family for the Novolizer multi-dose dry powder
      inhaler.
AB  - In this study, the design of a multifarious classifier family for different
      applications is described. The main design and development steps are presented as
      well as some special techniques that have been applied to achieve preset
      objectives. It is shown by increasing the number of air supply channels to the
      classifier chamber (from 2 to 8), that the fine particle losses from adhesion
      onto the classifier walls can be reduced from 75% to less than 5% of the real
      dose for soft (spherical) agglomerates. By applying a bypass flow that is
      arranged as a co-axial sheath of clean air around the aerosol cloud from the
      classifier, the airflow resistance of the classifier can be controlled over a
      relatively wide range of values (0.023-0.041 kPa(0.5) min l(-1)). This, without
      affecting the fine particle dose or increasing the fine particle losses in the
      inhaler. Moreover, the sheath flow can be modelled to reduce the depositions in
      the induction port to the cascade impactor or in the patient's mouth, which are
      the result of back flows in these regions. The principle of powder induced
      pressure drop reduction across a classifier enables assessment of the amount of
      powder in the classifier at any moment during inhalation, from which classifier
      loading (from the dose system) and discharge rates can be derived. This principle
      has been applied to study the residence time of a dose in the classifier as
      function of the carrier size fraction and the flow rate. It has been found that
      this residence time can be controlled in order to obtain an optimal balance
      between the generated fine particle fraction and the inhalation manoeuvre of the
      patient. A residence time between 0.5 and 2 s at 60 l/min is considered
      favourable, as this yields a high fine particle dose (depending on the type of
      formulation used) and leaves sufficient inhaled volume for particle transport
      into the deep lung.

PMID- 16442250
TI  - Differential effects of iontophoretic in vivo application of the GABA(A)
      antagonists bicuculline and gabazine in sensory cortex.
AB  - We have compared the effects of microiontophoretic application of the GABA(A)
      receptor antagonists bicuculline (BIC) and gabazine (SR95531) on responses to
      pure tones and to sinusoidally amplitude-modulated (AM) tones in cells recorded
      extracellularly from primary auditory cortex (AI) of Mongolian gerbils. Besides
      similar effects in increasing spontaneous and stimulus-evoked activity and their
      duration, both drugs elicited differential effects on spectral tuning and
      synchronized responses to AM tones. In contrast to gabazine, iontophoresis of the
      less potent GABA(A)-antagonist BIC often resulted in substantial broadening of
      frequency tuning for pure tones and an elimination of synchronized responses to
      AM tones, particularly with high ejecting currents. BIC-induced effects which
      could not be replicated by application of gabazine were presumably due to the
      well-documented, non-GABAergic side-effects of BIC on calcium-dependent potassium
      channels. Our results thus provide strong evidence that GABA(A)-mediated
      inhibition in AI does not sharpen frequency tuning for pure tones, but rather
      contributes to the processing of fast temporal modulations of sound envelopes.
      They also demonstrate that BIC can have effects on neuronal response selectivity
      which are not due to blockade of GABAergic inhibition. The results have profound
      implications for microiontophoretic studies of the role of intracortical
      inhibition in sensory cortex.

PMID- 16442252
TI  - Effects of Liuwei Dihuang decoction on ion channels and synaptic transmission in
      cultured hippocampal neuron of rat.
AB  - The effect of Liuwei Dihuang decoction (LW), a traditional Chinese medicine (TCM)
      prescription, on voltage-dependent currents and synaptic transmission were
      investigated in cultured hippocampal neurons of rat by whole-cell patch clamp
      recording technique. After application with serum from LW-treated rats, termed LW
      containing serum (LWCS) for 48 h, the amplitude of delay rectifying K+ current
      (IK) and voltage-gated Ca2+ current (ICa) decreased. While the frequency of
      spontaneous excitatory post-synaptic current (sEPSC) and miniature excitatory
      post-synaptic current (mEPSC) increased significantly. Yet the amplitude of
      voltage-depended Na+ current (INa) and transient outward K+ current (IA),
      membrane capacitance and resistance remained unchanged. The results indicated
      that LWCS possessed the effect of modulating or improving neuronal and synaptic
      function, which possibly contribute to the cognition enhancing effect of LW.

PMID- 16442251
TI  - Cochlear microdialysis for quantification of dexamethasone and fluorescein entry
      into scala tympani during round window administration.
AB  - Before new drugs for the treatment of inner ear disorders can be studied in
      controlled clinical trials, it is important that their pharmacokinetics be
      established in inner ear fluids. Microdialysis allows drug levels to be measured
      in perilymph without the volume disturbances and potential cerebrospinal fluid
      contamination associated with fluid sampling. The aims of this study were to
      show: (i) that despite low recovery rates from miniature dialysis probes,
      significant amounts of drug are removed from small fluid compartments, (ii) that
      dialysis sampling artifacts can be accounted for using computer simulations and
      (iii) that microdialysis allows quantification of the entry rates through the
      round window membrane (RWM) into scala tympani (ST). Initial experiments used
      microdialysis probes in small compartments in vitro containing sodium
      fluorescein. Stable concentrations were observed in large compartments (1000
      microl) but significant concentration declines were observed in smaller
      compartments (100, 10 and 5.6 microl) comparable to the size of the inner ear.
      Computer simulations of these experiments closely approximated the experimental
      data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone
      dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM
      of guinea pigs. Perilymph concentration in the basal turn of ST was monitored
      using microdialysis. The fluorescein concentration reached after 200 min
      application (585+/-527 microg/ml) was approximately twice that of dexamethasone
      phosphate (291+/-369 microg/ml). Substantial variation in concentrations was
      found between animals by approximately a factor of 34 for fluorescein and at
      least 41 for dexamethasone phosphate. This is, to a large extent, thought to be
      the result of the RWM permeability varying in different animals. It was not
      caused by substance analysis variations, because two different analytic methods
      were used and the concentration ratio between the two substances remained nearly
      constant across the experiments and because differences were apparent for the
      repeated samples obtained in each animal. Interpretation of the results using
      computer simulations allowed RWM permeability to be quantified. It also
      demonstrated, however, that cochlear clearance values could not be reliably
      obtained with microdialysis because of the significant contribution of dialysis
      to clearance. The observed interanimal variation, e.g., in RWM permeability, is
      likely to be clinically relevant to the local application of drugs in patients.

PMID- 16442253
TI  - Anti-diabetes and hypoglycaemic properties of Hemionitis arifolia (Burm.) Moore
      in rats.
AB  - Hemionitis arifolia, a folklore anti-diabetes fern, was evaluated for its
      hypoglycaemic and anti-diabetic properties using rats. Glucose lowering effect
      and anti-diabetes activity were studied using glucose tolerance test in normal
      rats and alloxan diabetic rats, respectively. When different extracts were
      tested, the ethanol and, to some extent, the water extracts were found to lower
      the levels of blood glucose in glucose fed rats. The ethanol extract showed
      optimum activity at 200 mg/kg. The extract exhibited only marginal hypoglycaemic
      activity in overnight fasted normal rats and it was devoid of conspicuous toxic
      symptoms in sub-acute toxicity evaluation in mice. When the alcohol extract was
      fractionated by sequential solvent extraction, the activity was found in ethyl
      acetate fraction (50 mg/kg). This fraction containing steroids and coumarins
      showed anti-diabetes activity in alloxan diabetic rats as judged from serum
      glucose levels, liver glycogen content and body weight. This fraction is an
      attractive material for further research vis-a-vis drug development.

PMID- 16442254
TI  - Changes in secretory cell turnover, and mitochondrial oxidative damage in the
      mouse mammary gland during a single prolonged lactation cycle suggest the
      possibility of accelerated cellular aging.
AB  - Milk synthesis by the mammary gland declines during prolonged lactation despite
      the continued suckling stimulus and complete removal of mammary secretions.
      Although this process has been hypothesized to result from cellular aging there
      has been no reported analysis of aging markers in the lactating mammary gland.
      The goal of these studies was to relate lactation performance in the mouse during
      a single prolonged lactation cycle to changes in mammary development and
      mitochondrial oxidative damage. During an artificially prolonged lactation cycle,
      the capacity of the dams to support litter growth decreased over time. This
      decrease was associated with decreased mammary epithelial content. Cell
      proliferation, along with the percentage of mammary progenitor cells, was high
      during early lactation, but low during prolonged lactation. Apoptosis increased
      during prolonged lactation. Oxidative damage to mitochondrial DNA increased
      during the early postpartum period and remained elevated through the end of the
      cycle. In contrast oxidative damage to mitochondrial protein was high during
      early lactation and decreased through mid lactation to increase again with
      prolonged lactation. The results suggest that a single prolonged lactation cycle
      may replicate on an accelerated basis some of the changes that occur with a
      lifetime of aging in organs possessing more stable cell populations.

PMID- 16442255
TI  - WITHDRAWN: Reply to Letter to the Editor.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 16442257
TI  - Magnetic resonance first pass perfusion imaging for detecting coronary artery
      disease.
AB  - Magnetic resonance first pass perfusion imaging can be used to detect
      abnormalities in myocardial blood flow. This technique involves imaging the first
      pass of gadolinium based contrast through the myocardium. Images are initially
      read qualitatively for areas of reduced signal intensity. Additionally, at our
      institution a quantitative method is applied that can aid both detection and
      diagnosis of perfusion defects. This method involves fitting the myocardial
      signal intensity curves and then calculates absolute myocardial blood flow. Our
      approach to first pass perfusion imaging will be reviewed. Magnetic resonance
      first pass perfusion imaging has a complimentary role with coronary angiography
      either non-invasively using CT or with catheterization. Perfusion imaging defines
      the physiology and angiography in the anatomy of coronary artery disease.

PMID- 16442256
TI  - Accuracy of 16-slice multi-detector CT to quantify the degree of coronary artery
      stenosis: assessment of cross-sectional and longitudinal vessel reconstructions.
AB  - BACKGROUND: Sixteen-slice multi-detector computed tomography (MDCT) permits
      reliable noninvasive detection of significant coronary stenosis based on
      qualitative visual assessment. The purpose of this study was to determine the
      accuracy of MDCT to quantify the degree of coronary stenosis as compared to
      quantitative coronary angiography (QCA) using two different reconstruction
      methods. METHODS: We studied 69 coronary artery lesions from 38 consecutive
      patients that underwent 16-slice MDCT as a part of research study, which enrolled
      consecutive subjects scheduled for clinically indicated invasive coronary
      angiography. Nine coronary artery lesions with motion artifacts, heavily
      calcified plaques or stents were excluded from the analysis. The degree of
      stenosis was calculated by two independent readers non-blinded to the location of
      the stenosis, but blinded to the results of the QCA. MDCT luminal diameters were
      measured in cross-sectional multi-planar reformatted (CS-MPR) images created
      perpendicular to the centerline of the vessel and in 5 mm thin-slab maximum
      intensity projections (MIP) parallel to the long axis of the vessel. Both MDCT
      methods were compared against QCA. RESULTS: The mean degree of stenosis as
      measured by MDCT was closely correlated to QCA for both methods (CS-MPR versus
      QCA: 61 +/- 23% versus 64 +/- 29%; r2 = 0.83, p < 0.001 and MIP versus QCA: 64 +/
      22% versus 64 +/- 29%; r2 = 0.84, p < 0.001 for MIP. Bland-Altman analysis
      demonstrated a negative bias of the degree of stenosis of -2.8 +/- 12% using CS
      MPR and a minimally positive bias of 0.6 +/- 12% for MIP. In stratified analysis
      for lesion severity (mild, 0-40%; moderate, 41-70% or severe, > 70%) the
      agreement between both CS-MPR and MIP was high when compared to QCA (kappa = 0.74
      and 0.71, respectively). CONCLUSION: Multi-detector spiral CT permits accurate
      quantitative assessment of the degree of coronary stenosis in selected data sets
      of sufficient quality using both cross-sectional and longitudinal vessel
      reconstructions.

PMID- 16442258
TI  - MDCT-based coronary angiography: a Rosetta stone for understanding coronary
      disease?

PMID- 16442259
TI  - Molecular phylogeny based on the 16S rRNA gene of elite rhizobial strains used in
      Brazilian commercial inoculants.
AB  - Nitrogen is often a limiting nutrient, therefore the sustainability of food
      crops, forages and green manure legumes is mainly associated with their ability
      to establish symbiotic associations with stem and root-nodulating N2-fixing
      rhizobia. The selection, identification and maintenance of elite strains for each
      host are critical. Decades of research in Brazil resulted in a list of strains
      officially recommended for several legumes, but their genetic diversity is poorly
      known. This study aimed at gaining a better understanding of phylogenetic
      relationships of 68 rhizobial strains recommended for 64 legumes, based on the
      sequencing of the 16S rRNA genes. The strains were isolated from a wide range of
      legumes, including all three subfamilies and 17 tribes. Nine main phylogenetic
      branches were defined, seven of them related to the rhizobial species:
      Bradyrhizobium japonicum, B. elkanii, Rhizobium tropici, R. leguminosarum,
      Sinorhizobium meliloti/S. fredii, Mesorhizobium ciceri/M. loti, and Azorhizobium
      caulinodans. However, some strains differed by up to 35 nucleotides from the type
      strains, which suggests that they may represent new species. Two other clusters
      included bacteria showing similarity with the genera Methylobacterium and
      Burkholderia, and amplification with primers for nifH and/or nodC regions was
      achieved with these strains. Host specificity of several strains was very low, as
      they were capable of nodulating legumes of different tribes and subfamilies.
      Furthermore, host specificity was not related to 16S rRNA, therefore evolution of
      ribosomal and symbiotic genes may have been diverse. Finally, the great diversity
      observed in this study emphasizes that tropics are an important reservoir of N2
      fixation genes.

PMID- 16442260
TI  - Folic acid pretreatment prevents the reduction of Na(+),K(+)-ATPase and
      butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia.
AB  - The main objective of the present study was to evaluate the effect of folic acid
      pretreatment on parietal cortex Na(+),K(+)-ATPase and serum butyrylcholinesterase
      activities in rats subjected to acute hyperhomocysteinemia. Animals were
      pretreated daily with an intraperitoneal injection of folic acid (5 mg/kg) or
      saline from the 22th to the 28th day of age. Twelve hours after the last
      injection of folic acid or saline, the rats received a single subcutaneous
      injection of homocysteine (0.6 micromol/g of weight body) or saline and were
      killed 1h later. Serum was collected and the brain was quickly removed and
      parietal cortex dissected. Results showed that acute homocysteine administration
      significantly decreased the activities of Na(+),K(+)-ATPase and
      butyrylcholinesterase on parietal cortex and serum, respectively. Furthermore,
      folic acid pretreatment totally prevented these inhibitory effects. We also
      evaluated the effect of acute homocysteine administration on some parameters of
      oxidative stress, namely thiobarbituric acid-reactive substances and total thiol
      content in parietal cortex of rats. No alteration of these parameters were
      observed in parietal cortex of homocysteinemic animals, indicating that these
      oxidative stress parameters were probably not responsible for the reduction of
      Na(+),K(+)-ATPase and butyrylcholinesterase activities. The presented results
      confirm previous findings that acute hyperhomocysteinemia produces an inhibition
      of Na(+),K(+)-ATPase and butyrylcholinesterase activities and that pretreatment
      with folic acid prevents such effects. Assuming that homocysteine might also
      reduce the activities of these enzymes in human beings, our results support a new
      potential therapeutic strategy based on folic acid supplementation to prevent the
      neurological damage found in hyperhomocysteinemia.

PMID- 16442261
TI  - Assessing the diagnostic experiences of a small sample of parents of children
      with autism spectrum disorders.
AB  - Although no Canadian studies have been conducted, studies suggest parents of
      children with autism experience difficulties obtaining a diagnosis for their
      child. Fifty-six parents of children with autism completed three questionnaires
      providing information on the families' demographics, parents' experiences
      throughout the diagnostic process, and their child's autistic symptomatology.
      These parents experienced significant difficulties obtaining a diagnosis for
      their child. Parents saw an average of 4.5 professionals, and waited almost 3
      years to receive a diagnosis following their first visit to a professional
      regarding their child's development. The impact of autistic symptomatology on the
      diagnostic process is discussed.

PMID- 16442262
TI  - Role of death receptor and mitochondrial pathways in conventional chemotherapy
      drug induction of apoptosis.
AB  - The molecular mechanism underlying chemotherapy-induced apoptosis is often
      debated because of contradicting reports of its signaling pathway. The focus of
      this ongoing debate is on the requirement of a death receptor and its role in
      subsequent activation of caspase-8. Understanding the precise mechanism
      responsible for apoptosis and identifying molecules targeted by chemotherapy will
      allow us to develop better therapeutic strategies that target the inherent
      abnormalities of cancer cells. To show conventional chemotherapy drugs can
      trigger the caspase cascade, including caspase-8, -9, -3 and DNA fragmentation
      factor, Jurkat T leukemia cells were treated with cisplatin or etoposide in a
      dose-dependent and a time-dependent manner. Cisplatin and etoposide all induced
      apoptosis in wild-type Jurkat T leukemia cells. On the other hand, when a pan
      caspase inhibitor zVAD-FMK was pretreated, apoptosis did not occur, indicating
      that these chemotherapy drugs mediated caspase-dependent apoptosis. However, the
      chemotherapy drug induction of apoptosis was not inhibited by treatment of zIETD
      FMK, a caspase-8 inhibitor. There was no difference in cell death between wild
      type and caspase-8 or FADD-deficient Jurkat cells after treatment of chemotherapy
      drug. In addition, cisplatin-induced apoptosis is abrogated by the overexpression
      of either Bcl-2 or Bcl-x(L), which diminished changes of mitochondrial membrane
      potential and decreased the amount of cytochrome c released from mitochondria.
      Again, cisplatin-induced apoptosis was not diminished by c-FLIP-overexpression,
      whereas the c-FLIP-overexpressing cells were less sensitive to TRAIL-induced
      apoptosis than the wild type cells. Therefore, these results indicate that
      conventional chemotherapy drug-triggered apoptosis is indispensable, and its
      pathway is independent of the death receptor.

PMID- 16442263
TI  - Essential requirement for Rho family GTPase signaling in Pax3 induced mesenchymal
      epithelial transition.
AB  - We previously showed that the transcription factor Pax3 regulates mesenchymal-to
      epithelial transition (MET) in cultured osteogenic Saos-2 cells. Herein we
      demonstrate that Pax3 induced MET in these cells requires intact Pax3 DNA binding
      motifs and is associated with the altered expression and activity of numerous
      proteins involved in signal transduction pathways that regulate cytoskeleton
      remodeling, the majority of which were not previously detected by mRNA expression
      array analysis. Proper levels of active Rho GTPases are essential for Pax3
      induced MET. Rac activity and actomyosin contractility via Rho/ROCK signaling are
      required for the formation of circumferential actin bundles, epithelial discoid
      cell shape and the regulation of membrane protrusions. Precise spatial activation
      of Rho GTPase signaling components is also paramount for MET. Endogenous PAK2,
      Rac1 and PIX, a Rac/Cdc42-GEF, localize to focal adhesions. Dynamic localization
      of PAK and PIX to focal adhesions is required for Pax3 induced MET and is
      dependent on full PAK activity because kinase dead or GTPase-binding deficient
      mutants of PAK sequester PIX at focal adhesions and disrupt Pax3 induced
      phenotypic MET. All together, our results define roles for Rho GTPases and their
      effectors in MET and newly identify proteins and signal transduction cascades
      regulated by Pax3.

PMID- 16442264
TI  - Improved sedation for oral surgery by combining nitrous oxide and intravenous
      Midazolam: a randomized, controlled trial.
AB  - The objective is to investigate whether sedation techniques for oral surgery can
      be improved by combining the use of inhalation of nitrous oxide/oxygen with
      intravenous Midazolam. Prospective, randomized controlled clinical trial:
      Patients requiring extractions or surgery were randomly allocated to subgroups
      receiving either intravenous Midazolam or nitrous oxide/oxygen or a combined
      technique using nitrous oxide/oxygen and intravenous Midazolam. Safety
      parameters, amount of sedative agents administered, recovery time and co
      operation scores were recorded. Patients receiving the combined sedation
      technique were initially titrated with 10% nitrous oxide, increasing by
      increments of 10% up to a maximum of 40% nitrous oxide and 60% oxygen. Midazolam
      was then titrated (initially 2 mg wait 2 min with increments of 1mg every minute
      until appropriately sedated) whilst still administering 40% nitrous oxide. When a
      combined technique of N(2)O/O(2) and Midazolam was used there was a statistically
      significant reduction in the amount of Midazolam required to achieve effective
      sedation (P<0.001), an overall significant reduction in recovery time (P<0.001)
      and a significant improvement in co-operation (P<0.01) and arterial oxygen
      saturation (P<0.001). This combined technique was found to be safe and reliable,
      requiring reduced doses of Midazolam and demonstrable improvement in patient
      recovery and co-operation.

PMID- 16442265
TI  - Associations of symptoms, psychosocial function and hope with qualities of self
      experience in schizophrenia: comparisons of objective and subjective indicators
      of health.
AB  - While changes in self-experience have been suggested to be an important element
      of recovery from severe mental illness, little is known about how qualities of
      self-experience are linked with other indicators of health including objective
      measures such as symptoms profiles and subjective measures such as hope. To
      examine these issues the narratives of self and illness of 65 persons with
      schizophrenia spectrum disorder were obtained prior to entry into rehabilitation
      and rated using the Scale to Assess Narrative Development (STAND). STAND scores
      were then compared with concurrent assessments of hope assessed with the Beck
      Hopelessness Scale (BHS), psychosocial function using the Quality of Life Scale
      (QOLS) and symptom profile defined categorically using the Positive and Negative
      Syndrome Scale (PANSS). Results suggest that higher ratings of the STAND were
      associated with greater expectations of perseverance on the BHS and higher levels
      of psychosocial function on the QOL. Lower symptom profiles were similarly linked
      with higher STAND scores. Results suggest qualities of self-experience expressed
      within personal narratives are linked to symptom profiles and subjective
      assessments of health. Theoretical and clinical implications are discussed.

PMID- 16442266
TI  - Sustained attention deficits in relation to psychometrically identified
      schizotypy: evaluating a potential endophenotypic marker.
AB  - Sustained attention deficits have been posited as a potential endophenotypic
      marker of vulnerability to schizophrenia. Prior studies have indicated that
      schizophrenia patients, their first-degree relatives, and psychosis-prone
      individuals, identified on the basis of measures of positive schizotypy, have
      demonstrated sustained attention deficits. To date, there have been no published
      reports of sustained attention deficits in individuals with negative schizotypy,
      as measured by the revised Social Anhedonia Scale. In this study, we examined
      sustained attention, measured with the CPT-Identical Pairs version, in 160
      individuals with elevated scores on the Chapman Perceptual Aberration and/or
      Magical Ideation Scales, 96 individuals with elevated scales on the Social
      Anhedonia Scale, and 137 controls. Both psychosis-prone groups performed more
      poorly than the controls in terms of discrimination ability, as measured by d',
      though the groups did not differ in terms of either their reaction time or
      overall response criterion (lnbeta). These results provide evidence that both
      positive and negative aspects of schizotypy are associated with sustained
      attention deficits, as measured by the Continuous Performance Test. The findings
      add to the converging evidence indicating that sustained attention deficits are a
      potential endophenotypic indicator of a schizophrenia diathesis.

PMID- 16442267
TI  - Runx1 transcription factor is involved in the regulation of KAP5 gene expression
      in human hair follicles.

PMID- 16442268
TI  - Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances
      the canonical pathway of Wnt signaling in normal keratinocytes.
AB  - BACKGROUND: Bone morphogenetic protein-2 (BMP-2) and Wnt are involved in the
      normal development and tumorigenesis of several organs, and in the development of
      skin and skin appendages as a morphogen. However, the crosstalk between BMP-2 and
      the Wnt/beta-catenin signaling pathway is not clear. OBJECTIVE: We examined BMP-2
      dependent expression of Wnt and its receptor frizzled in normal human
      keratinocytes. METHODS: The mRNA expression of the Wnt and frizzled families was
      analyzed by reverse transcription-polymerase chain reaction (RT-PCR) or
      ribonuclease protection assay. beta-Catenin expression was measured using RT-PCR
      and Western blotting. T-cell factor/lymphoid enhancing factor activity was
      analyzed using the luciferase reporter assay. RESULTS: We detected the expression
      of Wnt-2b/13, -4, -5a, -5b, -7a, -7b, and -10a, frizzled-1, -4, -5, -6, -8, -9,
      and -10, MFRP, and SFRP-1/SARP-2 in keratinocytes. BMP-2 increased Wnt-2b/13, 
      5b, and -7b, and frizzled-6, -8, and -10. Conversely, BMP-2 suppressed Wnt-10a
      and SFRP-1/SARP-2. Although Wnt-4 expression was not affected by BMP-2 in
      confluent conditioned keratinocytes, BMP-2 suppressed cell density-dependent Wnt
      4 induction. The transcriptional activity of TCF/LEF, which is a target of the
      canonical Wnt pathway, was upregulated by BMP-2 in both time- and dose-dependent
      manners. However, BMP-2-dependent differentiation of keratinocytes suppressed
      TCF/LEF transcriptional activity. CONCLUSION: These results suggest that BMP-2
      modulates the expression of molecules involved in Wnt signaling, and activates
      the canonical Wnt pathway in normal human keratinocytes. Moreover, Wnt signaling
      may be influenced by the fate of keratinocytes, such as proliferation, migration,
      and differentiation.

PMID- 16442269
TI  - Possible role of endoplasmic reticulum stress in the pathogenesis of Darier's
      disease.

PMID- 16442270
TI  - ECNP consensus meeting March 2003 guidelines for the investigation of efficacy in
      substance use disorders.

PMID- 16442271
TI  - Synaptic remodeling induced by axotomy of superior cervical ganglion neurons:
      Involvement of metalloproteinase-2.
AB  - We previously demonstrated the involvement of the dystrophin-dystroglycan (Dys
      DG) complex in the stabilization of intraganglionic synapses in rodent superior
      cervical ganglion (SCG) by investigating changes in the organization of their
      post-synaptic apparatus induced either by ganglionic neuron axotomy or by the
      lack of Dys in genetically dystrophic mdx mice, or by the combination of the two.
      A role of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the degradation
      of DG and, hence, in disrupting the connection between the extracellular matrix
      (ECM) and the cortical cytoskeleton, has recently been proposed. We hypothesized
      that the degradation by MMPs of ECM proteins and DG in ganglionic neurons may be
      involved in injury-induced synaptic detachment observed in rodent SCG. In this
      review, we report changes in MMP-2 and in the proteins involved in one of the
      enzymatic cascades of activation induced by axotomy of rat SCG neurons. This will
      be preceded by a description of our previous observations that led to investigate
      the role of MMP-2 in this experimental model.

PMID- 16442272
TI  - Synaptic information processing by astrocytes.
AB  - Glial cells were classically considered as supportive cells that do not
      contribute to information processing in the nervous system. However, considerable
      amount of evidence obtained by several groups during the last few years has
      demonstrated the existence of a bidirectional communication between astrocytes
      and neurons, which prompted a re-examination of the role of glial cells in the
      physiology of the nervous system. This review will discuss recent advances in the
      neuron-to-astrocyte communication, focusing on the recently reported properties
      of the synaptically evoked astrocyte Ca2+ signal that indicate that astrocytes
      show integrative properties for synaptic information processing. Indeed, we have
      recently shown that hippocampal astrocytes discriminate between the activity of
      different synapses, and respond selectively to different axon pathways.
      Furthermore, the astrocyte Ca2+ signal is modulated by the simultaneous activity
      of different synaptic inputs. This Ca2+ signal modulation depends on cellular
      intrinsic properties of the astrocytes, is bidirectionally regulated by the level
      of synaptic activity, and controls the spatial extension of the intracellular
      Ca2+ signal. Consequently, we propose that astrocytes can be considered as
      cellular elements involved in information processing by the nervous system.

PMID- 16442273
TI  - [Neonatal lupus syndromes].
AB  - Children born from mothers positive for autoantibodies against SSA/Ro and/or anti
      SSB/La ribonucleoproteins may develop heart conduction tissue damage resulting in
      atrioventricular block and/or transient skin rash, liver enzyme abnormalities and
      anaemia/thrombocytopenia. Additional transient electrocardiographic abnormalities
      (sinus bradycardia, QT interval prolongation) have been reported. Such clinical
      and laboratory manifestations are included in the so-called neonatal lupus
      syndromes, independently whether the mother is suffering from a systemic
      autoimmune disease or is totally asymptomatic. The prevalence of the congenital
      heart block is around 2%, of neonatal rash around 20%, while laboratory
      abnormalities in asymptomatic babies can be detected in up to 40% of cases. The
      risk of recurrence of complete heart block is almost 10 times higher in the
      following pregnancies. Most of the mothers are asymptomatic at delivery and are
      identified only by the birth of an affected child. Their long-term outcome is
      generally more reassuring than previously assumed. Serial echocardiograms and
      obstetric sonograms, performed at least every 2 weeks, starting from 16 weeks
      gestation, are recommended in anti-Ro/SSA positive pregnant women: the goal is to
      detect early fetal abnormalities, that might precede complete atrioventricular
      block and that might be a target for preventive therapy. Transplacental passage
      of maternal anti-SSA/Ro -SSB/La IgG is thought to be pivotal in inducing tissue
      damage. However, the discordant appearance of the syndrome in twins does suggest
      a role also for fetal or environmental factors.

PMID- 16442274
TI  - A microplate assay for the screening of ADAMTS-4 inhibitors.
AB  - Aggrecanase plays a major role in cartilage proteoglycan degradation in rheumatic
      diseases such as osteoarthritis and rheumatoid arthritis. The search of new
      inhibitors of aggrecanase activity necessitates a robust assays in order to be
      able to screen large numbers of compounds. We present in this paper an assay
      based on the cleavage of His-tagged aggrecan interglobular domain by N- and C-
      terminus truncated, active aggrecanase-1/ADAMTS-4, with formation of the
      aggrecanase-specific ARGSV neoepitope. This is detected by anti-ARGSV antibody,
      in turn recognized by a fluorescent anti-IgG. Furthermore, the formation of the
      reaction products was confirmed by high-pressure capillary electrophoresis. This
      assay allows the rapid screening of aggrecanase inhibitors in a 96-well plate
      format, allowing an immediate transposition to high-throughput scale up.

PMID- 16442276
TI  - EDC-mediated DNA attachment to nanocrystalline CVD diamond films.
AB  - Chemical vapour deposited (CVD) diamond is a very promising material for
      biosensor fabrication owing both to its chemical inertness and the ability to
      make it electrical semiconducting that allows for connection with integrated
      circuits. For biosensor construction, a biochemical method to immobilize nucleic
      acids to a diamond surface has been developed. Nanocrystalline diamond is grown
      using microwave plasma-enhanced chemical vapour deposition (MPECVD). After
      hydrogenation of the surface, 10-undecenoic acid, an omega-unsaturated fatty
      acid, is tethered by 254 nm photochemical attachment. This is followed by 1-ethyl
      3-[3-dimethylaminopropyl]carbodiimide (EDC)-mediated attachment of amino (NH(2))
      modified dsDNA. The functionality of the covalently bound dsDNA molecules is
      confirmed by fluorescence measurements, PCR and gel electrophoresis during 35
      denaturation and rehybridisation steps. The linking method after the fatty acid
      attachment can easily be applied to other biomolecules like antibodies and
      enzymes.

PMID- 16442275
TI  - Higher patient perceived side effects related to higher daily doses of inhaled
      corticosteroids in the community: a cross-sectional analysis.
AB  - The range and extent of inhaled corticosteroid (ICS) side effects experienced by
      patients in the general community are likely to be underestimated. AIMS: To
      identify the side effects of ICS perceived by patients in the community and,
      through the use of a self-report questionnaire, measure their intensity,
      prevalence and relationship with daily medication dose. METHODS: Focus groups and
      in-depth interviews were conducted to identify side effects that patients
      associated with their use of ICS. In an international multicentre cross-sectional
      survey, 395 inhaler users from community pharmacy (mean age 50, 53% female),
      divided into 4 daily dosage groups (beta2-agonist without ICS n=66, beclometasone
      dipropionate (BDP) equivalent ICS low dose 400 microg, n=109; mid dose 401-800
      microg, n=151; and high dose>800 microg, n=69) reported how much they were
      affected by these side effects on a 7-point Likert scale. RESULTS: Focus groups
      and interviews revealed 57 side effects that were associated with ICS use. Cross
      sectional survey results showed significant differences in side effect perception
      between the four dosage groups for 31 items (all P0.01) and a rising intensity
      with increasing ICS dose for total side effect score (P<0.001). For ICS users
      reporting the most bothersome side effects (scoring 3 on 0-6 scale) there was a
      rising prevalence as ICS dose increased for 34 items. A multivariate model
      confirmed that mid and high ICS dosages were statistically significantly
      associated with side effect perception after controlling for the other factors
      and covariates. CONCLUSIONS: Higher daily ICS doses were associated with a higher
      intensity and a higher prevalence of many patient perceived side effects, lending
      support to the call for dose titration in clinical practice. Results indicate the
      usefulness of patient self-report scales for understanding the burden of side
      effects of ICS in the community.

PMID- 16442277
TI  - Molecular dimensions and their distributions in early folding intermediates.
AB  - The integration of ultrafast mixing technology with bright X-ray sources at
      synchrotrons and with sophisticated fluorescence methods is yielding quantitative
      insights into the dimensions of unfolded proteins and transient intermediates
      that appear during the earliest stages of folding. Time-resolved Forster
      resonance energy transfer and small-angle X-ray scattering techniques, which are
      sensitive to the distributions of distances, can also elucidate the nature of
      processes otherwise obscured in measurements of a single ensemble-averaged
      optical property. These two approaches have recently been applied to the protein
      folding problem. In particular, progress has been made in characterizing the
      dimensions of unfolded states, and discriminating between barrierless and barrier
      limited collapse of the unfolded state at the beginning of the folding reaction.

PMID- 16442278
TI  - Beta-sheet folding mechanisms from perturbation energetics.
AB  - Amide backbone and sidechain mutagenesis data can be used in combination with
      kinetic and thermodynamic measurements to understand the energetic contributions
      of backbone hydrogen bonding and the hydrophobic effect to the acquisition of
      beta-sheet structure. For example, it has been revealed that loop 1 of the WW
      domain forms in the transition state, consistent with the emerging theme that
      reverse turn formation is rate limiting in beta-sheet folding. A distinct subset
      of WW domain residues principally influences thermodynamic stability by forming
      hydrogen bonds and hydrophobic interactions that stabilize the native state.
      Energetic data and sequence mining reveal that only a small subset of the
      molecular information contained in sequences or observed in high-resolution
      structures is required to generate folded functional beta-sheets, consistent with
      evolutionary robustness.

PMID- 16442279
TI  - Can we rationally design promiscuous drugs?
AB  - Structure-based drug design is now used widely in modern medicinal chemistry. The
      application of structural biology to medicinal chemistry has heralded the
      "rational drug design" vision of discovering exquisitely selective ligands.
      However, recent advances in post-genomic biology are indicating that
      polypharmacology may be a necessary trait for the efficacy of many drugs,
      therefore questioning the "one drug, one target" assumption of current rational
      drug design. By combining advances in chemoinformatics and structural biology, it
      might be possible to rationally design the next generation of promiscuous drugs
      with polypharmacology.

PMID- 16442280
TI  - Compression of fractionated sun-cured and dehydrated alfalfa chops into cubes-
      specific energy models.
AB  - The objective of this study was to determine the specific energy requirements for
      the compression of fractionated sun-cured and dehydrated alfalfa chops, when
      subjected to different pressures and holding times. The compression behavior of
      fractionated sun-cured and dehydrated alfalfa chops was studied using a single
      cubing unit capable of making one cube in a single stroke of the plunger. The
      cube die dimensions were 30 mm x 30 mm in cross-section and an effective depth of
      compression of 0.38 m. The initial moisture content of dehydrated and sun-cured
      chops were 6% and 7% (wb), respectively. A stack of two sieves (instead of five)
      was used along with a pan to achieve leaf and stem separation. The nominal
      opening sizes of two sieves with square holes were 3.96 and 1.17 mm,
      respectively. Leaf and stem fractions were combined later to obtain five
      different samples each for sun-cured and dehydrated alfalfa with leaf content
      ranging from 0% to 100% by mass in increments of 25%. The chop moisture content
      and preheat temperature before compaction was 10% (wb) and 75 degrees C,
      respectively. The cube die temperature was maintained at 90+/-5 degrees C. The
      mass of chops used for making each cube was 23+/-02 g. A hydraulic press was used
      to apply 9.0, 12.0 and 14.0 MPa of pressures through a plunger. After
      compression, the plunger was held in place for 10 and 30s, before the compacted
      forage was extracted. Empirical equations were fitted to the data relating
      specific energy for cube making to pressure, residence time, and leaf content.

PMID- 16442282
TI  - Pyrolysis and combustion behaviour of coal-MBM blends.
AB  - In the present work, thermogravimetric analysis was employed in order to
      investigate the behaviour of MBM and their blends with Greek brown coal, under
      pyrolysis and combustion conditions. MBM presented enhanced pyrolysis rates
      reflecting its high volatile and low ash contents compared to Greek brown coal.
      Increased conversion rates were observed when MBM was added in the brown coal
      sample. Significant interactions were detected between the two fuel blend
      components leading to significant deviations from the expected behaviour. The
      catalytic effect of mineral matter on the pyrolysis of MBM resulted in reaction
      rate decrease and DTG curve shift to lower temperatures for the demineralised
      MBM. Alterations in the combustion process due to the mineral matter were minimal
      when testing the blends. Interactions maintained during combustion and lower
      reactivity of MBM was achieved due to the reduced oxygen content.

PMID- 16442281
TI  - Study of banana and coconut fibers Botanical composition, thermal degradation and
      textural observations.
AB  - Four fibers from banana-trees (leaf, trunk) and coconut-tree (husk, fabric) were
      examined before their incorporation in cementitious matrices, in order to prepare
      insulating material for construction. Their botanical compositions have been
      determined following a method described previously. Thermal degradation of these
      fibers were studied between 200 and 700 degrees C under nitrogen gas flow.
      Temperature of pyrolysis was the experimental parameter investigated. The solid
      residues obtained were analyzed by classical elemental analysis, Fourier
      Transform Infra Red (FTIR) spectroscopy and were observed by Scanning Electron
      Microscopy (SEM). This study has shown (1) the relation between botanical,
      chemical composition with both localization of fibers in the tree and type of
      tree; (2) the rapid and preferential decomposition of banana fibers with
      increasing temperature of pyrolysis and (3) the rough samples are made of hollow
      fibers.

PMID- 16442283
TI  - Synthesis of benz[d]indeno[1,2-b]pyran-5,11-diones: versatile intermediates for
      the design and synthesis of topoisomerase I inhibitors.
AB  - A method has been developed that relies on a two-step, one-pot condensation
      between phthalide and 2-carboxybenzaldehydes to provide benz[d]indeno[1,2-b]pyran
      5,11-diones in a multi-gram fashion. Treatment of these compounds with a primary
      amine allows rapid access to various N-substituted indenoisoquinolines, whose in
      vitro anticancer activity and topoisomerase I inhibition have been evaluated.

PMID- 16442284
TI  - Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: side chain
      exploration.
AB  - The synthesis and structure-activity relationships of the 4- and 6-substituents
      of 2,4-diaminopyrimidine-based growth hormone secretagogue receptor (GHS-R)
      antagonists are described. Diaminopyrimidines with 6-norbornenyl (4n) and 6
      tetrahydrofuranyl (4p) substitutents were found to exhibit potent GHS-R
      antagonism and good selectivity (approximately 1000-fold) against dihydrofolate
      reductase.

PMID- 16442285
TI  - Benzoxazole benzenesulfonamides are novel allosteric inhibitors of fructose-1,6
      bisphosphatase with a distinct binding mode.
AB  - We have identified benzoxazole benzenesulfonamide 1 as a novel allosteric
      inhibitor of fructose-1,6-bisphosphatase (FBPase-1). X-ray crystallographic and
      biological studies of 1 indicate a distinct binding mode that recapitulates
      features of several previously reported FBPase-1 inhibitor classes.

PMID- 16442286
TI  - Solid-phase synthesis of 1,3,4-oxadiazoline-5-thione derivatives from resin-bound
      acylhydrazines.
AB  - A new strategy for solid-phase synthesis of 2,5-disubstituted 1,3,4-oxadiazoles
      has been developed. The 1,3,4-oxadiazoline-5-thione derivatives were synthesized
      from resin-bound acylhydrazines in several steps providing 78-88% overall yields
      and excellent purity.

PMID- 16442287
TI  - How cyclodextrins can mask their toxic effect on the blood-brain barrier.
AB  - The toxicity of monosubstituted n-alkyldimethylammonium-beta-cyclodextrins (DMA
      C(n)-CD with n=2, 4 and 12) towards endothelial cells of an in vitro model of the
      blood-brain barrier (BBB) was evaluated and compared to that of the native beta
      CD. DMA-C(12)-CD was found to be non-toxic below 10mM due to the self-inclusion
      of the alkyl chain in the CD cavity. A high percentage of passage (30%) of DMA
      C(12)-CD through the endothelial cells has been measured.

PMID- 16442288
TI  - Hydantoin derivatives as non-peptidic inhibitors of Ras farnesyl transferase.
AB  - 1,3,5,5-Tetrasubstituted 2,4-imidazolinedione (hydantoin) derivatives were
      evaluated as Ftase inhibitors. Potent Ftase inhibitors without thiol or peptide
      were obtained in three steps.

PMID- 16442289
TI  - QSAR models of quail dietary toxicity based on the graph of atomic orbitals.
AB  - Graphs of atomic orbitals (GAOs) have been used to represent molecular
      structures. We describe rules to convert the labelled hydrogen-filled graphs
      (LHFGs) into GAOs. The GAO is one possible way of taking account of the structure
      of atoms (i.e., atomic orbitals, such as 1s(1), 2p(2) and 3d(10)) for QSPR/QSAR
      analyses. Optimization of correlation weights of local invariants (OCWLI) of the
      LHFGs and the GAOs was used to obtain a method of quail dietary toxicity
      modelling. Statistical characteristics of the models based on the OCWLI of GAO
      are better than those based on the OCWLI of the LHFGs.

PMID- 16442290
TI  - Novel non-benzimidazole chk2 kinase inhibitors.
AB  - In a recent paper, [Arienti, K. L.; Brunmark, A.; Axe, F. U.; McClure, K. M.;
      Lee, A.; Blevitt, J.; Neff, D. K.; Huang, L.; Crawford, S.; Chennagiri, R. P.;
      Karlsson, L.; Brietenbucher, J. G. J. Med. Chem.2005, 48, 1873], we described the
      discovery of a class of benzimidazole chk2 kinase inhibitors, exemplified by
      compound 1, which had radio-protective effects in human T-cells subjected to
      ionizing radiation. Here, a series of non-benzimidazole analogs intended to
      define the scope of the SAR about this new series of inhibitor, and allow for
      refinement of the binding model of these compounds to the chk2 kinase is
      described.

PMID- 16442291
TI  - Volumetric analysis of a specific language region - the planum temporale.
AB  - Planum temporale volumes were determined for 42 control children (ages 4.2-15.7
      years) using magnetic resonance imaging. The mean left planum temporale volume
      was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3
      (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co
      variance (ANCOVA) showed that the absolute and proportional planum temporale
      volumes were not significantly associated with age or gender. We also
      demonstrated a reproducible method for planum temporale volume measurement by
      acquiring images in the coronal plane and then visualising the sagittal plane to
      improve accuracy for the posterior border.

PMID- 16442292
TI  - Design, synthesis, and biological evaluation of combretastatin nitrogen
      containing derivatives as inhibitors of tubulin assembly and vascular disrupting
      agents.
AB  - A series of analogs with nitro or serinamide substituents at the C-2'-, C-5'-, or
      C-6'-position of the combretastatin A-4 (CA4) B-ring was synthesized and
      evaluated for cytotoxic effects against heart endothelioma cells, blood flow
      reduction to tumors in SCID mice, and as inhibitors of tubulin polymerization.
      The synthesis of these analogs typically featured a Wittig reaction between a
      suitably functionalized arylaldehyde and an arylphosphonium salt followed by
      separation of the resultant E- and Z-isomers. Several of these nitrogen-modified
      CA4 derivatives (both amino and nitro) demonstrate significant inhibition of
      tubulin assembly as well as cytotoxicity and in vivo blood flow reduction. 2'
      Aminostilbenoid 7 and 2'-amino-3'-hydroxystilbenoid 29 proved to be the most
      active in this series. Both compounds, 7 and 29, have the potential for further
      pro-drug modification and development as vascular disrupting agents for treatment
      of solid tumor cancers and certain ophthalmological diseases.

PMID- 16442293
TI  - 3D QSAR on a library of heterocyclic diamidine derivatives with antiparasitic
      activity.
AB  - African trypanosomes, Trypanosoma brucei rhodesiense (TBR) and Trypanosoma brucei
      gambiense (TBG), affect hundreds of thousands of lives in tropical regions of the
      world. The toxicity of the diamidine pentamidine, an effective drug against TBG,
      necessitates the design of better drugs. An orally effective prodrug of the
      diamidine, furamidine (DB75), presently scheduled for phase III clinical trials,
      has excellent activity against TBG with toxicity lower than that of pentamidine.
      As part of an effort to develop additional and improved diamidines against
      African trypanosomes, CoMFA and CoMSIA 3D QSAR analyses have been conducted with
      furamidine and a set of 25 other structurally related compounds. Two different
      alignment strategies, based on a putative kinetoplast DNA minor groove target,
      were used. Due to conserved electrostatic properties across the compounds, models
      that used only steric and electronic properties did not perform well in
      predicting biological results. An extended CoMSIA model with additional
      descriptors for hydrophobic, donor, and acceptor properties had good predictive
      ability with a q2=0.699, r2=0.974, SEE, standard error of estimate=0.1, and
      F=120.04. The results have been used as a guide to design compounds that,
      potentially, have better activity against African trypanosomes.

PMID- 16442294
TI  - Retrospective estimation of the concentration of 241Pu in air sampled at a
      Belgrade site following the Chernobyl accident.
AB  - The surface air activity concentration of 241Pu for the period May 01-15, 1986,
      for a monitoring site in Vinca, Belgrade was retrospectively estimated. The
      results were obtained by re-measurement of plutonium fraction alpha-spectrometric
      sources, with 236Pu as a tracer, used almost 13 years earlier for the
      determination of (239,240)Pu concentration in surface air immediately after the
      Chernobyl accident. The estimated 241Pu concentration, based on the 241Am in
      growth method for air samples, ranged from 240 to 7800 microBq/m3. The average
      activity ratio 241Pu/(239,240)Pu originating from the Chernobyl accident at
      Belgrade site was approximately 100 at the collection time.

PMID- 16442295
TI  - Decreased association of the transcription factor Sp1 with genes downregulated in
      Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disease caused by expansion of a
      polyglutamine tract within the huntingtin protein. Transcriptional dysregulation
      has been implicated in HD pathogenesis; recent evidence suggests a defect in Sp1
      mediated transcription. We used chromatin immunoprecipitation (ChIP) assays
      followed by real-time PCR to quantify the association of Sp1 with individual
      genes. We find that, despite normal protein levels and normal to increased
      overall nuclear binding activity, Sp1 has decreased binding to specific promoters
      of susceptible genes in transgenic HD mouse brain, in striatal HD cells, and in
      human HD brain. Genes whose mRNA levels are decreased in HD have abnormal Sp1-DNA
      binding, whereas genes with unchanged mRNA levels have normal levels of Sp1
      association. Moreover, the altered binding seen with Sp1 is not found with
      another transcription factor, NF-Y. These findings suggest that mutant huntingtin
      dissociates Sp1 from target promoters, inhibiting transcription of specific
      genes.

PMID- 16442296
TI  - Complete aortic root reimplantation facilitates preservation of the aortic valve.
AB  - The optimal technique for preservation of a retainable aortic valve is yet to be
      defined. We present a new facilitated procedure allowing for reimplantation of
      the complete aortic root in selected patients with acute type A aortic dissection
      or ascending aortic aneurysm.

PMID- 16442297
TI  - Mitral regurgitation progression following isolated coronary artery bypass
      surgery: frequency, risk factors, and potential prevention strategies.
AB  - BACKGROUND: Though de novo mitral regurgitation (MR) is frequently seen in
      patients who have undergone coronary artery bypass surgery (CABG), its incidence,
      predictors, and mechanisms are not known. METHODS: Our surgical registry was
      screened for patients undergoing isolated CABG who had preoperative and
      postoperative resting echocardiograms performed at our institution with <or=2+ MR
      preoperatively. This yielded 438 patients. Progression to 3-4+ MR post-CABG was
      correlated with clinical, electrocardiographic, echocardiographic, and operative
      variables. RESULTS: New 3-4+ MR developed in 11 (10%) of the 108 patients with no
      prior MR, 21 of the 180 (12%) patients with pre-CABG 1+ MR, and 37 of the 150
      (25%) patients with pre-CABG 2+ MR. MR progression correlated with female gender
      (42% vs 27%, p=0.01), history of renal insufficiency (12% vs 5%, p=0.05), prior
      CABG (30% vs 17%, p=0.01), lack of beta-blocker use (19% vs 35%, p=0.008), lower
      incidence of significant PDA stenosis grafted (88% vs 98%, p=0.003), lower
      preoperative LVEF (42+/-19% vs 50+/-17%, p=0.001), larger LV size (p=0.01), pre
      CABG MR grade (p=0.0002), and pre-CABG presence of LBBB block (20% vs 4%,
      p<0.0001). Independent predictors of MR progression, pre-CABG, were female gender
      (p=0.002), history of renal insufficiency (p=0.05), lack of beta-blocker use
      (p=0.006), MR grade (p=0.02), and presence of LBBB (p=0.005). CONCLUSION:
      Development of significant MR following isolated CABG is common and may be
      related to incomplete myocardium revascularization, especially in the PDA area
      and LV remodeling. Preoperative, beta-blocker use may be protective against its
      development.

PMID- 16442299
TI  - Mild--moderate ischemic mitral regurgitation: should it be treated together with
      CABG?

PMID- 16442298
TI  - Sildenafil extends survival and graft function in a large animal lung
      transplantation model.
AB  - OBJECTIVE: Restoring intracellular cGMP and inducing NO-synthesis attenuates
      ischemia-associated early pulmonary allograft dysfunction. Phosphodiesterase-5
      (PDE), predominantly expressed in lung tissue, plays a pivotal role in modulating
      the cGMP/NO-synthase pathway in endothelial and epithelial cells. In this study,
      we evaluate the effect of employing sildenafil (Viagra), a specific inhibitor of
      PDE-5, to counteract ischemia/reperfusion (I/R) injury in a single lung
      transplantation model of extended ischemia. METHODS: Donor animals (weight
      matched outbred pigs, 28-35 kg) in the treatment group (I) (n=5) were injected
      with 0.7 mg sildenafil/kg into the pulmonary artery (PA) prior to inflow
      occlusion. For perfusion, Perfadex, containing 0.7 mg sildenafil/l was used, and
      the graft stored at 1 degrees C in the perfusion solution. After 24h ischemia,
      unilateral left lung transplantation was performed. Starting at reperfusion,
      group I received continuous sildenafil (0.7 mg sildenafil/kg), over 6h. Except
      for the sildenafil application, the control group (II) (n=4) was treated
      identically (PGE1 was injected into the PA). One hour after reperfusion, the
      right main bronchus (MB) and right PA were occluded. Over the next 5h,
      cardiopulmonary parameters (systemic atrial, PA, central venous, left atrial
      pressure, pCO(2), pO(2)) were measured, including extravascular lung water
      (EVLW). Thiobarbituric acid-reactive substance assay (TBARS) and myeloperoxidase
      (MPO) analysis from lung tissue were run. RESULTS: All recipients of group I
      survived the 6-h reperfusion period; in contrast, all control animals died within
      1-2h after occlusion of the right side. In comparison to a marked rise in
      pulmonary vascular resistance (PVR) in group II (>1000 dynescm(-5)), PVR in group
      I remained stable, moderately elevated from baseline (baseline: 150-180 dynescm(
      5) vs endpoint: 1000 dynescm(-5)). EVLW in group I did not increase during
      reperfusion (baseline: 6.75+/-1.4 mg/kg vs endpoint: 6.7+/-1.0mg/kg), in contrast
      to group II, where pulmonary edema at 2-h reperfusion preceded terminal graft
      failure (group I: 9.7+/-0.1mg/kg vs group II: 6.48+/-1.8 mg/kg). Tissue reactive
      free radicals at endpoint measurement in group I did not differ significantly
      from native tissue. Yet, when compared to specimen taken from group II at time of
      terminal graft failure, a significant increase in free radicals was noted (group
      I: 13.8+/-1.6 pmol/g vs group II: 18.5+/-3.0 pmol/g, p<0.05). CONCLUSION:
      Sildenafil treatment prevents terminal early graft failure, allowing lung
      transplantation after 24-h ischemia time. Reperfusion edema was strikingly
      diminished, preserving pulmonary structural and functional integrity while
      prolonging graft ischemia time. Employing the established PDE-5 inhibitor
      sildenafil during lung perfusion, storage, and implantation, ischemic tolerance
      may be extended and early graft function improved.

PMID- 16442301
TI  - Changes in ultraviolet absorbance and hence in protective efficacy against lipid
      peroxidation of organic sunscreens after UVA irradiation.
AB  - Owing to the spectral distribution of solar UV, the UVA component of sunlight is
      now believed to be the main cause of photoaging and photocarcinogenesis and is
      much more effective than UVB in inducing peroxidative damage. Consequently, most
      skin care cosmetic products now include UVA filters in their formulations along
      with UVB filters. These modern sunscreens should provide and maintain their
      initial absorbance, hence protection, throughout the entire period of exposure to
      sunlight. However, not all UVA and UVB filters are sufficiently photostable. In
      this study, we examine the correlation between the photochemical degradation of
      sunscreen agents under UVA irradiation, with particular reference to the UVA
      absorber 4-tert-butyl-4'-methoxydibenzoylmethane, alone and in combination with
      other organic UV filters (2-ethylhexyl 4 methoxycinnamate and 2-ethylhexyl 2
      cyano-3,3-diphenylacrylate) and their ability to prevent UVA-induced lipid
      peroxidation. Since antioxidants are also added to formulations to deactivate
      free radicals generated during UVA exposure, vitamin E and the synthetic
      antioxidant, bis(2,2,6,6-tetramethyl-1-oxyl-piperidine-4-yl)sebacate, a nitroxide
      derivative, were also included in this study. By using simple in vitro tests, the
      results show that a decrease in spectral absorbance of the UV filters correlates
      in most cases with increased UVA-induced lipid peroxidation; this depends on the
      specific UV absorber analysed and also on whether they are alone or in
      combination. Furthermore, the combined presence or absence of antioxidants has a
      profound effect on this oxidative event. In particular, the nitroxide appears to
      be a more efficient photo-antioxidant than vitamin E. Similar experiments were
      also performed under natural sunlight and the results obtained did not differ
      substantially from those performed under UVA. The results presented and discussed
      in this work may help in understanding the effects of UVA/UVB absorbers and
      antioxidants upon the level of UV-induced ROS generated under UVA exposure and in
      natural sunlight which could be relevant for improving the photoprotection and
      efficacy of skin care cosmetic formulations.

PMID- 16442300
TI  - The effect of Ge, Si and Sn phthalocyanine photosensitizers on cell proliferation
      and viability of human oesophageal carcinoma cells.
AB  - The photodynamic activity of water soluble mixed sulfonated
      metallophthalocyanines complexes: GePcSmix, SnPcSmix and SiPcSmix on human
      oesophageal carcinoma (SNO) cells are reported, and compared with the activity of
      the unmetallated H2PcSmix and of the newly synthesized water soluble adjacently
      substituted binaphthalo phthalocyanine (complex 3). The alkaline phosphate (ALP)
      showed damage to the cell membrane in the presence of complex 3 without
      irradiation. The GePcSmix complex caused a relatively large increase in
      inflammation and a high intracellular ATP.

PMID- 16442302
TI  - Simulations of ion trapping in a micrometer-sized cylindrical ion trap.
AB  - We have performed detailed SIMION simulations of ion behavior in micrometer-sized
      cylindrical ion traps (r0 = 1 microm). Simulations examined the effects of ion
      and neutral temperature, the pressure and nature of cooling gas, ion mass, trap
      voltage and frequency, space-charge, fabrication defects, and other parameters on
      the ability of micrometer-sized traps to store ions. At this size scale voltage
      and power limitations constrain trap operation to frequencies about 1 GHz and rf
      amplitudes of tens of volts. Correspondingly, the pseudopotential well depth of
      traps is shallow, and thermal energies contribute significantly to ion losses.
      Trapping efficiency falls off gradually as qz approaches 0.908, possibly
      complicating mass-selective trapping, ejection, or quantitation. Coulombic
      repulsion caused by multiple ions in a small-volume results in a trapping limit
      of a single ion per trap. If multiple ions are produced in a trap, all but one
      ion are ejected within a few microseconds. The remaining ion tends to have
      favorable trapping parameters and a lifetime about hundreds of microseconds;
      however, this lifetime is significantly shorter than it would have been in the
      absence of space-charge. Typical microfabrication defects affect ion trapping
      only minimally. We recently reported (IJMS 2004, 236, 91-104) on the construction
      of a massively parallel array of ion traps with dimensions of r0 = 1 microm. The
      relationship of the simulations to the expected performance of the
      microfabricated array is discussed.

PMID- 16442303
TI  - Relating chromatographic retention and electrophoretic mobility to the ion
      distribution within electrosprayed droplets.
AB  - Ions that are observed in a mass spectrum obtained with electrospray mass
      spectrometry can be assumed to originate preferentially from ions that have a
      high distribution to the surface of the charged droplets. In this study, a
      relation between chromatographic retention and electrophoretic mobility to the
      ion distribution (derived from measured signal intensities in mass spectra and
      electrospray current) within electrosprayed droplets for a series of
      tetraalkylammonium ions, ranging from tetramethyl to tetrapentyl, is presented.
      Chromatographic retention in a reversed-phase system was taken as a measure of
      the analyte's surface activity, which was found to have a large influence on the
      ion distribution within electrosprayed droplets. In addition, different transport
      mechanisms such as electrophoretic migration and diffusion can influence the
      surface partitioning coefficient. The viscosity of the solvent system is affected
      by the methanol content and will influence both diffusion and ion mobility.
      However, as diffusion and ion mobility are proportional to each other, we have,
      in this study, chosen to focus on the ion mobility parameter. It was found that
      the influence of ion mobility relative to surface activity on the droplet surface
      partitioning of analyte ions decreases with increasing methanol content. This
      effect is most probably coupled to the decrease in droplet size caused by the
      decreased surface tension at increasing methanol content. The same observation
      was made upon increasing the ionic strength of the solvent system, which is also
      known to give rise to a decreased initial droplet size. The observed effect of
      ionic strength on the droplet surface partitioning of analyte ions could also be
      explained by the fact that at higher ionic strength, a larger number of ions are
      initially closer to the droplet surface and, thus, the contribution of ionic
      transport from the bulk liquid to the liquid/air surface interface (jet and
      droplet surface), attributable to migration or diffusion will decrease.

PMID- 16442304
TI  - Application of a linear ion trap/orbitrap mass spectrometer in metabolite
      characterization studies: examination of the human liver microsomal metabolism of
      the non-tricyclic anti-depressant nefazodone using data-dependent accurate mass
      measurements.
AB  - We report herein, facile metabolite identification workflow on the anti
      depressant nefazodone, which is derived from accurate mass measurements based on
      a single run/experimental analysis. A hybrid LTQ/orbitrap mass spectrometer was
      used to obtain accurate mass full scan MS and MS/MS in a data-dependent fashion
      to eliminate the reliance on a parent mass list. Initial screening utilized a
      high mass tolerance ( approximately 10 ppm) to filter the full scan MS data for
      previously reported nefazodone metabolites. The tight mass tolerance reduces or
      eliminates background chemical noise, dramatically increasing sensitivity for
      confirming or eliminating the presence of metabolites as well as isobaric forms.
      The full scan accurate mass analysis of suspected metabolites can be confirmed or
      refuted using three primary tools: (1) predictive chemical formula and
      corresponding mass error analysis, (2) rings-plus-double bonds, and (3) accurate
      mass product ion spectra of parent and suspected metabolites. Accurate mass
      characterization of the parent ion structure provided the basis for assessing
      structural assignment for metabolites. Metabolites were also characterized using
      parent product ion m/z values to filter all tandem mass spectra for
      identification of precursor ions yielding similar product ions. Identified
      metabolite parent masses were subjected to chemical formula calculator based on
      accurate mass as well as bond saturation. Further analysis of potential
      nefazodone metabolites was executed using accurate mass product ion spectra.
      Reported mass measurement errors for all full scan MS and MS/MS spectra was <3
      ppm, regardless of relative ion abundance, which enabled the use of predictive
      software in determining product ion structure. The ability to conduct
      biotransformation profiling via tandem mass spectrometry coupled with accurate
      mass measurements, all in a single experimental run, is clearly one of the most
      attractive features of this methodology.

PMID- 16442305
TI  - The fragmentation of ethoxylated surfactants by AP-MALDI-QIT.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has become
      an important technique to characterize the chemical structure of industrial
      polymer materials. MALDI methods have been developed to address a broad variety
      of different polymer materials containing different chemistries. One of the key
      aspects of the typical MALDI experiment is the generation of intact ions. The
      development of Atmospheric Pressure (AP) MALDI quadrupole ion trap (QIT)
      instruments has opened another channel to obtaining MS/MS experiments for polymer
      samples. These experiments provide a new method to obtain chemical structure
      information from MALDI experiments. Collision-Induced Dissociation (CID) provides
      an improved MALDI MS/MS experiment that can be done on readily available mass
      spectrometers. AP MALDI QIT techniques have been successfully applied to a
      variety of synthetic polymers. This work explores the applicability of AP MALDI
      QIT methods to relatively low molecular weight ethoxylated surfactants. In these
      experiments we show the CID fragmentation mass spectra on some ethoxylated
      surfactants, and demonstrate the existence of analyte matrix clusters.

PMID- 16442306
TI  - Characterization of cardiolipin from Escherichia coli by electrospray ionization
      with multiple stage quadrupole ion-trap mass spectrometric analysis of [M - 2H +
      Na]- ions.
AB  - We report a multiple-stage ion-trap (IT) mass spectrometric approach with
      electrospray ionization (ESI) for structural characterization of the [M - 2H +
      Na]- ion of cardiolipin (CL), a 1,3-bisphosphatidyl-sn-glycerol that consists of
      four fatty acyl chains and three glycerol backbones designated as A, B, and
      central glycerol, respectively (see Scheme 1). Following collisionally activated
      dissociation (CAD), the [M - 2H + Na]- ions of CL yield two prominent fragment
      ions that arise from the differential losses of the diacylglycerol moieties
      containing A or B glycerol, respectively. The tentative assignment of the two
      phosphatidyl moieties attached to the 1'- or 3'-position of the central glycerol
      is based on the observation that the ions arising from loss of the diacylglycerol
      moiety containing glycerol B is more abundant than that containing glycerol A.
      The structures of the above two ions, including the identities of the fatty acyl
      substituents and the position of fatty acyl substituents on the glycerol
      backbones (glycerol A and B) are determined by MS3 experiments that give spectra
      comprising several sets of prominent ions informative for the structural
      assignment of the fatty acyl substituents on the glycerol A and glycerol B. This
      method permits the structures of CL in a mixture isolated from Escherichia coli,
      including species that consist of various isomers, to be unveiled in detail.

PMID- 16442308
TI  - Purification and characterization of the CK2alpha'-based holoenzyme, an isozyme
      of CK2alpha: a comparative analysis.
AB  - Protein kinase CK2 (former name: "casein kinase 2") is a pivotal and ubiquitously
      expressed member of the eukaryotic protein kinase superfamily. It predominantly
      exists as a heterotetrameric holoenzyme composed of two catalytic subunits
      (CK2alpha) and two regulatory subunits (CK2beta). In higher animals two paralog
      catalytic chains-abbreviated CK2alpha and CK2alpha'--exist which can combine with
      CK2beta to three isoforms of the holoenzyme: CK2alpha(2)beta(2),
      CK2alpha(2)(')beta(2), and CK2alphaalpha(')beta(2). While CK2alpha and the
      "normal" holoenzyme CK2alpha(2)beta(2) have been extensively characterized in
      vitro and in vivo, little is known about the enzymological properties of
      CK2alpha' and the "alternative" holoenzyme CK2alpha(2)(')beta(2) and about their
      specific physiological roles. A major reason for this lack of knowledge is the
      fact that so far CK2alpha' rather than CK2alpha has caused serious stability and
      solubility problems during standard heterologous expression procedures. To
      overcome them, we developed a preparation scheme for CK2alpha(2)(')beta(2) from
      Homo sapiens in catalytically active form based on two critical steps: first
      expression of human CK2alpha' as a well soluble fusion protein with the maltose
      binding protein (MBP) and second proteolytic cleavage of CK2alpha'-MBP in the
      presence of human CK2beta so that CK2alpha' subunits are incorporated into
      holoenzyme complexes directly after their release from MBP. This successful
      strategy which may be adopted in comparably difficult cases of protein/protein
      complex preparation is presented here together with evidence that the CK2alpha'
      based and the CK2alpha-based holoenzymes are similar concerning their catalytic
      activities but are significantly different with respect to some well-known CK2
      properties like autophosphorylation and supra-molecular aggregation.

PMID- 16442307
TI  - Analysis of oxysterols by electrospray tandem mass spectrometry.
AB  - Oxysterols are oxygenated derivatives of cholesterol. They are intermediates in
      cholesterol excretion pathways and may also be regarded as transport forms of
      cholesterol. The introduction of additional hydroxyl groups to the cholesterol
      skeleton facilitates the flux of oxysterols across the blood brain barrier, and
      oxysterols have been implicated in mediating a number of cholesterol-induced
      metabolic effects. Oxysterols are difficult to analyze by atmospheric pressure
      ionization mass spectrometry on account of the absence of basic or acidic
      functional groups in their structures. In this communication, we report a method
      for the derivatization and analysis of oxysterols by electrospray mass
      spectrometry. Oxysterols with a 3beta-hydroxy-Delta5 structure were converted by
      cholesterol oxidase to 3-oxo-Delta4 steroids and then derivatized with the Girard
      P reagent to give Girard P hydrazones, which were subsequently analyzed by tandem
      mass spectrometry. The improvement in sensitivity for the analysis of 25
      hydroxycholesterol upon oxidation and derivatization was over 1000.

PMID- 16442309
TI  - Cloning, sequencing, expression, and characterization of protealysin, a novel
      neutral proteinase from Serratia proteamaculans representing a new group of
      thermolysin-like proteases with short N-terminal region of precursor.
AB  - The gene of Serratia proteamaculans proteinase, protealysin, was cloned,
      sequenced, and expressed in Escherichia coli. The gene encoded a precursor of 341
      amino acids (AAs) with a significant homology to thermolysin-like proteinases
      (TLPs). The molecular weight of the purified mature active recombinant protein
      was 32 kDa, the N-terminal amino acid sequence was AKTSTGGEVI. The optimum pH for
      azocasein hydrolysis by protealysin was seven and it was completely inhibited by
      o-phenanthroline. The enzyme hydrolyzed 3-(2-furyl)acryloyl-glycyl-L-leucine
      amide, the standard substrate for TLPs, with k(cat)/K(m) ratio of (2.52 +/- 0.02)
      x 10(2) M(-1) s(-1). Protealysin maturation removes 50 AA from the N-terminus of
      the precursor. The removed region had no similarity with the preprosequence of
      thermolysin (232 AA) but was homologous to some other TLPs. These proteins shared
      a conserved 7-AA motif near the initial methionine. Such motif was also found in
      some nonproteolytic putative proteins; two of them were eukaryotic.

PMID- 16442310
TI  - High-level bacterial expression and purification of human SirT2 protein for NMR
      studies.
AB  - Silent information regulator 2 (Sir2) proteins are a class of protein deacetylase
      enzymes that play key roles in transcriptional gene silencing, DNA repair, and
      aging. Here, we describe the high-level bacterial expression and purification of
      a human SirT2 construct that yields high resolution NMR spectra. By removing the
      N-terminal helix alpha0 and using Thioredoxin as a fusion partner, greater than
      10 mg/L of purified protein can be obtained from minimal media. The protein is
      fully functional and enables NMR-based screening and structural studies of this
      important protein.

PMID- 16442311
TI  - Extensive mitochondrial gene arrangements in coleoid Cephalopoda and their
      phylogenetic implications.
AB  - We determined the complete mitochondrial genomes of five cephalopods of the
      Subclass Coleoidea (Suborder Oegopsida: Watasenia scintillans, Todarodes
      pacificus, Suborder Myopsida: Sepioteuthis lessoniana, Order Sepiida: Sepia
      officinalis, and Order Octopoda: Octopus ocellatus) and used them to infer
      phylogenetic relationships. In our Maximum Likelihood (ML) tree, sepiids
      (cuttlefish) are at the most basal position of all decapodiformes, and oegopsids
      and myopsids form a monophyletic clade, thus supporting the traditional
      classification of the Order Teuthida. We detected extensive gene rearrangements
      in the mitochondrial genomes of broad cephalopod groups. It is likely that the
      arrangements of mitochondrial genes in Oegopsida and Sepiida were derived from
      those of Octopoda, which is thought to be the ancestral order, by entire gene
      duplication and random gene loss. Oegopsida in particular has undergone long
      range gene duplications. We also found that the mitochondrial gene arrangement of
      Sepioteuthis lessoniana differs from that of Loligo bleekeri, although they
      belong to the same family. Analysis of both the phylogenetic tree and
      mitochondrial gene rearrangements of coleoid Cephalopoda suggests that each
      mitochondrial gene arrangement was acquired after the divergence of each lineage.

PMID- 16442312
TI  - Molecular systematics of Hispaniolan pupfishes (Cyprinodontidae: Cyprinodon):
      implications for the biogeography of insular Caribbean fishes.
AB  - We used sequence variation in the mtDNA control-region and ND2 and cyt b genes to
      assess the systematics and biogeography of the five species of pupfish
      (Cyprinodon) on Hispaniola. These include four endemics, the relatively large
      bodied Cyprinodon bondi, Cyprinodon nichollsi, and Cyprinodon sp., each from a
      separate lake in southwestern Hispaniola, and Cyprinodon higuey from a coastal
      lake in eastern Hispaniola. The fifth species consists of coastal populations
      referable to Cyprinodon variegatus riverendi. The results indicate that
      Hispaniola has been invaded by at least two forms, first by a late Pliocene
      progenitor of Cyprinodon variegatus ovinus and the large-bodied Hispaniolan
      species, and, more recently, by one or more ancestral forms allied with
      Cyprinodon variegatus variegatus and C. v. riverendi. Levels of divergence
      indicate that large expanses of open sea have not acted as long-term barriers to
      inter-island dispersal of cyprinodontiform fishes. This study, together with the
      molecular systematics of other insular Caribbean fishes, indicates that most
      insular groups originated from late Neogene dispersal from the mainland. The
      patterns of mtDNA variation in Cyprinodon showed little congruence with the
      species/subspecies taxonomy.

PMID- 16442313
TI  - Molecular phylogeny and historical biogeography of the land snail genus
      Solatopupa (Pulmonata) in the peri-Tyrrhenian area.
AB  - The land snail genus Solatopupa consists of six species and has a peri-Tyrrhenian
      distribution; most of the species have a very narrow range and all of them except
      one (Solatopupa cianensis, which inhabits porphyritic rocks) are strictly bound
      to calcareous substrates. One species (Solatopupa guidoni) is limited to
      Sardinia, Corsica, and Elba Island. Because the potential for dispersal of these
      snails is low, the insular range of this species has been traditionally related
      to the Oligocenic detachment of the Sardinia-Corsica microplate from the Iberian
      plate and its subsequent rotation towards the Italian peninsula. In this study,
      we used sequences of three mitochondrial and one nuclear gene to reconstruct the
      evolutionary history of the genus. Our phylogenetic results are consistent with
      the genetic relationships found using allozymes, but contrast with the
      phylogenetic hypotheses based on karyology and morphology. Molecular clock
      estimates indicate that the main cladogenetic events in the genus occurred
      between the middle Miocene and the middle-late Pliocene. Patterns of phylogenetic
      relationships and geological considerations suggest that the cladogenesis of the
      genus can be explained by vicariant (tectonic) processes. Our datings do not
      support a causal relation between the split of S. guidoni from its continental
      sister taxon and the initial phases of the detachment of the Corsica-Sardinia
      microplate from the mainland. On the contrary, time estimates coincide with the
      very last phase of detachment of the microplate (from 5 to 3 Myrs ago). Overall,
      our molecular clock estimates are in good agreement with the latest geological
      views on the tectonic evolution of the peri-Tyrrhenian area.

PMID- 16442314
TI  - Antiepileptic drugs and liver disease.
AB  - Antiepileptic drugs (AEDs) are no longer restricted to the treatment of epilepsy.
      These are widely used in a broad spectrum of psychiatric and neurological
      disorders. Liver plays a major role in the metabolism of a majority of these
      drugs. Hepatotoxicity is rare, but a real concern when initiating therapy.
      Likewise, liver disease can adversely affect the biotransformation of some of
      these drugs. This manuscript addresses the significance of elevated liver enzymes
      associated with AED use, the role of therapeutic drug monitoring,
      pharmacokinetics during liver disease and potential risk of hepatotoxicity.

PMID- 16442315
TI  - Investigations in generalized osteoarthritis. Part 2: special histological
      features in generalized osteoarthritis (histological investigations in Heberden's
      nodes using a histological score).
AB  - OBJECTIVE: In accordance with the literature, our previous epidemiological,
      clinical and genetical investigations have confirmed a correlation between
      generalized osteoarthritis (GOA) and Heberden's nodes. Heberden's nodes can be
      considered as genetic markers for the existence of a generalized osteoarthritic
      predisposition. The present study's concern was to establish whether there are
      special histological features in this disease. METHODS: Layered sections of 218
      distal finger joints from 56 deceased persons were investigated using a
      histological-histochemical score modified by Mankin. RESULTS: In Heberden's
      nodes, we found all the typical degradative sequences of the osteoarthritic
      process but also some specific modifications. The osteoarthritis (OA) starts with
      a subchondral ossification and manifests a reactive tidemark flaking. At this
      time, the surface of the cartilage is not yet destroyed. Later on, there is
      progression of general degradation. Significant differentiation from the control
      group is possible using a histological score. CONCLUSIONS: In patients with
      Heberden's nodes, the OA starts with the subchondral ossification. Heberden's
      nodes are the specific manifestation of GOA in the distal finger joints. Further
      studies are therefore required to assess whether the same pathogenetic mechanism
      can be seen in OA of the large joints in GOA.

PMID- 16442316
TI  - High signal in knee osteophytes is not associated with knee pain.
AB  - OBJECTIVE: Our understanding of the local source of pain in osteoarthritis (OA)
      remains unclear. We undertook this study to determine if the presence of high
      signal osteophytes on magnetic resonance imaging (MRI) was associated with pain
      presence, location or severity. METHODS: Subjects were chosen from the Boston
      Osteoarthritis of the Knee Study, a natural history study of symptomatic knee OA.
      Assessments included knee MRI, pain assessments and information on weight and
      height. Osteophyte signal was defined as areas of increased signal intensity in
      the osteophyte on fat-suppressed T2 weighted images, and graded in the joint
      margins where osteophyte size is graded. All patients were evaluated with the
      frequent knee symptoms question for pain presence, the Western Ontario McMasters
      Osteoarthritis Index (WOMAC) for pain severity, and location of self-reported
      pain was recorded as present or absent based on locations identified on a
      standardized diagram. The osteophyte signal measures anywhere within one given
      knee were summed, creating an osteophyte signal aggregate. Logistic regression
      was conducted with quartile of osteophyte signal aggregate as the independent
      predictor and frequent knee symptom question as the dependent outcome.
      Association between quartile of osteophyte signal aggregate and pain severity on
      WOMAC was assessed using a linear regression. Logistic regression was used to
      evaluate the association between compartment-specific high-signal osteophytes
      aggregates (independent variable) and compartment-specific knee pain (dependent
      variable). Analyses were adjusted for gender, body mass index (BMI), and age.
      RESULTS: Two hundred and seventeen subjects were included in this analysis. They
      were predominantly male and 75% of subjects had radiographic tibio-femoral (TF)
      OA, and the remainder had patello-femoral (PF) radiographic OA. We did not find
      any association of high-signal osteophytes with presence of pain, pain severity
      or self-reported pain location. CONCLUSION: High-signal osteophytes detected on
      MRI are not associated with the presence of pain, pain severity or the self
      reported location of pain.

PMID- 16442317
TI  - Olfactory learning in the one-day old rat: reinforcing effects of isoproterenol.
AB  - Within 24 h of their birth-induced norepinephrine surge, rat pups were tested for
      effects of a beta-receptor agonist, isoproterenol, on olfactory learning.
      Experiment 1 found no effect of isoproterenol on conditioning by pairing an odor
      (CS) with intraoral saccharin infusions. There was, however, unexpectedly strong
      responding in the unpaired control condition, which had the same contingency
      between the CS and isoproterenol as the paired condition. Experiment 2 found that
      pairings of odor and isoproterenol alone were sufficient for enhancing responding
      to the odor. Experiment 3 determined that isoproterenol had acted independently
      as a US for associative conditioning rather than facilitating nonassociative
      learning by mere exposure to the odor. These effects of isoproterenol as a US are
      consistent with the results of previous studies with older rats.

PMID- 16442318
TI  - Glucocorticoid-induced impairment of long-term memory retrieval in rats: an
      interaction with dopamine D2 receptors.
AB  - This study investigated glucocorticoid-dopaminergic interactions in modulating
      retrieval of long-term memory in an inhibitory avoidance task. Young adult male
      rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock).
      On the retention test given 48 h after training, the latency to re-enter the dark
      compartment of the apparatus was recorded. Systemically administered
      corticosterone (1 or 3 mg/kg) given to rats 30 min before retention testing
      impaired their memory retrieval, but the lower dose was more effective than the
      higher one. Administration of the dopamine (DA) D2 receptor antagonist sulpiride
      (6 or 20 mg/kg) 30 min before corticosterone attenuated the impairing effects of
      corticosterone (1 mg/kg) on memory retrieval. Administration of the DA D1
      receptor antagonist SCH23390 (25 or 50 microg/kg) had no effect on corticosterone
      induced impairment of memory retrieval. Further, applied doses of sulpiride or
      SCH23390 alone were ineffective in modulating memory retrieval. These findings
      provide evidence for the existence of an interaction between glucocorticoids and
      DA D2 receptor on memory retrieval process.

PMID- 16442319
TI  - Nitric oxide-induced downregulation of leptin production by 3T3-L1 adipocytes.
AB  - Leptin secreted mainly by adipocytes plays an important role in insulin
      sensitivity in metabolic syndrome. Inducible nitric oxide synthase (iNOS) in 3T3
      L1 adipocytes is induced by lipopolysaccharide (LPS) and several proinflammatory
      cytokines such as tumor necrosis factor-alpha and interferon-gamma (IFN-gamma).
      Because the role of iNOS-derived nitric oxide (NO) in adipocyte function has not
      been fully clarified, the question that we addressed in the present study was
      whether iNOS-derived NO is involved in regulation of leptin secretion by
      adipocytes. Incubation of 3T3-L1 adipocytes for 12h with a mixture of IFN-gamma
      and LPS caused not only a 55% reduction in leptin secretion and a 52% reduction
      in leptin mRNA, but also significant induction of iNOS at both protein and mRNA
      levels. Inhibition of leptin secretion that had been induced by the IFN-gamma-LPS
      mixture was completely nullified by NOS inhibitors such as Nomega-monomethyl-L
      arginine and aminoguanidine. Treatment of adipocytes with NO donors such as an
      NONOate and S-nitrosoglutathione produced an effect on leptin secretion similar
      to that of the IFN-gamma-LPS mixture. It is likely therefore that NO mediates
      downregulation of leptin caused by the IFN-gamma-LPS mixture in 3T3-L1
      adipocytes, which suggests an important role for NO in adipocyte functions.

PMID- 16442321
TI  - A simple proof that third-order quadrupole perturbations of the NMR central
      transition of half-integral spin nuclei are zero.
AB  - It has been known for a long time that the third-order quadrupole corrections to
      transitions from mz=-n/2 to mz=+n/2 are zero in the NMR of half-integer nuclei.
      However, the derivation has relied on deriving the corrections to the energy
      levels through somewhat laborious calculations. Only when the transitions between
      the levels were calculated was it revealed that the corrections to the transition
      frequency were zero. In this paper, we use Liouville-space methods to work with
      the transitions directly. Application of a recently published [A.D. Bain, Exact
      calculation, using angular momentum, of combined Zeeman and quadrupolar
      interactions in NMR, Mol. Phys. 101 (2003) 3163-3175] selection rule for the
      quadrupole coupling leads to a very simple proof that third-order corrections to
      the central and other symmetrical transitions are zero. The simplicity of the
      proof suggests there is a fundamental symmetry involved.

PMID- 16442320
TI  - AMPA receptor-induced intracellular calcium response in the paraventricular
      nucleus is modulated by nitric oxide: calcium imaging in a hypothalamic
      organotypic cell culture model.
AB  - An organotypic cell culture (OCC) model of the rat hypothalamic paraventricular
      nucleus (PVN) was established to monitor intracellular calcium levels
      ([Ca(2+)](i)) of magnocellular neurons in response to glutamate and nitric oxide
      (NO). The histoarchitectural organization of these cultures was characterized
      either by immunohistochemical labeling of vasopressin, neuronal nitric oxide
      synthase (nNOS) and the neuronal marker NeuN or by the enzyme histochemical NADPH
      diaphorase staining. A distinct NeuN positive cell population in 14-days old
      OCC's was confirmed as being the PVN by its vasopressin- and nNOS-immunostained
      neurons as well as by its NADPH-diaphorase labeling. Life cell imaging was
      performed using the [Ca(2+)](i) sensor Fluo-4 to measure [Ca(2+)](i) transients
      in response to bath applications of glutamate, high potassium (60 mM), and ATP.
      The glutamate-induced [Ca(2+)](i) response was mimicked by AMPA but not NMDA in
      the PVN. NMDA, however, elicited a [Ca(2+)](i) transient in a different area of
      the OCC that corresponds to the suprachiasmatic nucleus indicating the potential
      effectiveness of the stimulus. The AMPA-receptor blocker NBQX abolished the
      glutamate-induced response in the PVN. An inhibition of endogenous NO production
      by the NOS inhibitor L-NAME decreased the amplitude of AMPA- and glutamate
      induced [Ca(2+)](i) rises. Taken together, these data suggest that AMPA mediates
      the glutamate-induced [Ca(2+)](i) rises within the PVN, where endogenous NO is
      able to modulate such glutamate signaling in OCC.

PMID- 16442322
TI  - D-2-hydroxyglutaric aciduria in three patients with proven SSADH deficiency:
      genetic coincidence or a related biochemical epiphenomenon?
AB  - Succinic semialdehyde dehydrogenase (SSADH) deficiency and D-2-hydroxyglutaric
      aciduria (D-2-HGA) are rare inborn errors of metabolism primarily revealed by
      urinary organic acid screening. Three patients with proven SSADH deficiency
      excreted, in addition to GHB considerable amounts of D-2-HG. We examined whether
      these patients suffered from two inborn errors of metabolism by measuring D-2-HG
      concentrations in the culture medium of cells from these patients. In addition,
      mutation analysis of the D-2-hydroxyglutarate dehydrogenase gene was performed.
      Normal concentrations of D-2-HG were measured in the culture media of fibroblasts
      or lymphoblasts derived from the three patients. In one patient, we found a
      heterozygous likely pathogenic mutation in the D-2-hydroxyglutarate dehydrogenase
      gene. These combined results argue against the hypothesis that the patients are
      affected with "primary" D-2-HGA in combination with their SSADH deficiency.
      Moderately increased levels of D-2-HG were also found in urine, plasma, and
      cerebrospinal fluid samples derived from 12 other patients with SSADH deficiency,
      revealing that D-2-HG is a common metabolite in this disease. The increase of D-2
      HG in SSADH deficiency can be explained by the action of hydroxyacid-oxoacid
      transhydrogenase, a reversible enzyme that oxidases GHB in the presence of 2
      ketoglutarate yielding SSA and D-2-HG.

PMID- 16442323
TI  - [Against routine use of misoprostol in term labor induction].

PMID- 16442325
TI  - [Comparison of two routine screening strategies for gestational diabetes
      mellitus: the experience of Jean-Verdier Hospital].
AB  - OBJECTIVE: Screening strategies for gestational diabetes mellitus are
      controversial. Thus, we sought to determine the benefits of universal screening.
      PATIENTS AND METHODS: Prospective study with 2121 women involved but 1610 really
      screened (75.9%). According to WHO's recommendations, the strategy implemented
      was one-step, universal screening with a 75g oral glucose tolerance test.
      Screening was performed between 24 and 28 weeks of gestation or earlier if risk
      factors were identified. Results were compared to previous year (2001) then only
      a selective screening was done. RESULTS: Application of universal screening
      increased the prevalence of gestational diabetes mellitus (8.39% to 15.65%). Out
      of the 252 patients with gestational diabetes, 66 did not display any identified
      risk factor (26.19%). Some new risk factors have been identified: age>30, Asian,
      Indian or Pakistan ethnies. If these new risk factors were applied, this super
      selective screening would have a sensibility of 96%. DISCUSSION AND CONCLUSION:
      Universal screening seems to be the most appropriate routine screening strategy
      because it is difficult to know exactly the specific risk factors of a population
      to do a super selective screening.

PMID- 16442326
TI  - [Laparoscopic management of ovarian cysts during pregnancy].
AB  - OBJECTIVE: To evaluate the results of laparoscopic surgery in the management of
      ovarian cysts in pregnant patients. PATIENTS AND METHODS: Retrospective study
      including 26 pregnant patients who underwent the laparoscopic management of
      ovarian cysts. The indications for surgery were persistent adnexal mass, abnormal
      ovarian cysts revealed by ultrasound examination, suspicion of cyst
      complications. The technique used, the immediate postoperative results and
      obstetrical outcomes were studied. RESULTS: Twelve patients were operated during
      the first trimester of pregnancy, 13 in the second, and one in the third
      trimester. A 12 mmHg CO2 pneumoperitoneum was created, using a Veress needle in
      22 cases, and an open technique in 4 cases. Trocar sites were decided according
      to the uterine size and to the cyst situation. A cystectomy was performed in 11
      cases, an adnexectomy in 7 cases, an oophorectomy in one case, a cyst aspiration
      with a biopsy of the cyst wall in 6 cases and an ovarian torsion removal in one
      case. A conversion to laparotomy was necessary in 3 cases. There were no
      immediate postoperative complications and obstetrical outcomes were good in all
      cases. DISCUSSION AND CONCLUSION: In pregnant patients, laparoscopic management
      of adnexal masses appears to be safe for both mother and child.

PMID- 16442327
TI  - [Acute fatty liver of pregnancy: a rare pathology of the third trimester].
AB  - Acute fatty liver of pregnancy is a rare clinical syndrome of pregnancy that
      occurs during the third trimester. Clinicians must have a high index of suspicion
      for this condition when a woman has nausea or vomiting during the last trimester.
      Early diagnosis and prompt delivery improve foetal and maternal prognosis. We
      report a case of a previously healthy 23-year-old woman who presented an acute
      fatty liver of pregnancy with intrauterine fetal death. Based on this experience
      as well as on medical literature, characteristics of this uncommon pathology are
      discussed.

PMID- 16442328
TI  - Predicting spontaneous termination of atrial fibrillation using the surface ECG.
AB  - By recognizing and characterizing conditions under which atrial fibrillation (AF)
      is likely to terminate spontaneously or be sustained, improved treatment of
      sustained AF may result and unnecessary treatment of self-terminating AF avoided.
      Time-frequency measures that characterize AF, such as fibrillatory frequency,
      amplitude, and waveform shape (exponential decay), are extracted from the
      residual ECG following QRST cancellation. Three complexity measures are also
      studied, characterizing the degree of organization of atrial activity. All
      measures are analysed using a training set, consisting of 20 recordings of AF
      with known termination properties, and a test set of 30 recordings. Spontaneous
      termination was best predicted by a low and stable fibrillatory frequency and a
      low exponential decay. Using these predictors, 90% of the test set was correctly
      classified into terminating and sustained AF. Neither fibrillation amplitude nor
      the complexity measures differed significantly between the two sets.

PMID- 16442329
TI  - The uncertainty of the pendulum method for the determination of the moment of
      inertia.
AB  - The purpose of this study was to quantify the uncertainty of the pendulum method
      for determining the moment of inertia of an object using various suspension
      distances. Experimental data were collected on a known geometric solid and
      partial differential equations were derived to calculate the uncertainty.
      Repeated measures were used to estimate the errors of the mass, period of
      oscillation, and distance measurements from the axis to the centre of mass. The
      results showed that the pendulum method was relatively insensitive to measurement
      errors of mass but was quite sensitive to errors in the period of oscillation. It
      was also found that the uncertainty of the pendulum method could be drastically
      reduced to less than 3% by suspending the object with the axis located at the
      radius of gyration. Most studies using the pendulum method to determine limb
      inertial properties have adopted a proximal suspension, including the often cited
      work by Dempster [Dempster WT. Space requirements for the seated operator. W ADC
      Technical Report 55-159. Ohio: Aero Medical Laboratory, Wright Air Development
      Centre, Air Research and Development Council, Wright-Patterson Air Force Base;
      1955]. The results suggest that validation of imaging techniques to determine
      inertial properties should use geometric solids in addition to the pendulum
      method where the object is suspended at a distance estimated to be the radius of
      gyration. It is further recommended that the uncertainty be reported whenever it
      is necessary to use the pendulum method.

PMID- 16442330
TI  - Climatic effects on incidence of sexual assault.
AB  - This study analysed the daily incidence of sexual assault in Greater Manchester
      with respect to the local weather conditions throughout the year 2002. Cases seen
      at the St. Mary's Sexual Assault Referral Centre (including police and self
      referred clients) for which the date of the assault was known were included in
      the study. The daily maximum, minimum, and mean temperature, rainfall, wind
      speed, and hours of sunshine recorded at Manchester Airport were used in
      correlation and regression analyses. Maximum temperature and hours of sunshine
      both had a statistically significant (p<0.05 and 0.01, respectively) positive
      relationship with the number of sexual assaults committed in a day.

PMID- 16442331
TI  - Accidental ligature strangulation due to electric grinder.
AB  - A young girl was accidentally strangled when her chunni (a piece of cloth worn
      around the neck by most Indian women) was caught in a moving electrical grinder.
      She was taken to the nearest hospital where she died within the next 9h,
      remaining unconscious throughout the hospital stay. Accidental strangulation of
      this kind due to household devices or machinery is extremely uncommon and to the
      best of our knowledge, this is the first case of its kind to be reported. The
      findings are presented.

PMID- 16442332
TI  - The relative risk of police use-of-force options: evaluating the potential for
      deployment of electronic weaponry.
AB  - An electronic weapon, the Taser M26, has recently entered the use-of-force
      continuum for police officers in England and Wales and is currently licensed for
      use by authorised firearms officers only. The aim of this report was to assess
      the relative risk of injury to officers and subjects of police use-of-force
      options and to evaluate whether the current positioning of the M26 in the use-of
      force hierarchy is appropriate. We analysed use-of-force data from
      Northamptonshire Police Force and M26 field use data from TASER International. We
      found officer injury rates associated with M26 deployment were lower than those
      for CS spray and baton use. Subject injury rates were lower in M26 deployment
      than in deployment of CS spray, batons or police dogs. We suggest that the M26
      should be made more widely available to police officers in the UK.

PMID- 16442333
TI  - The role of eustachian valve and patent foramen ovale in sudden death.
AB  - Sudden unexpected cardiac death is the leading cause of death in industrialized
      countries. Patent foramen ovale and eustachian valve are two of cardiac diseases
      and they may be associated with clinical disorders as embolism, stroke,
      plathypnea-orthodeoxia syndrome, carcinoid heart disease, atrial flutter and
      endocarditis. The literature for the roles of patent foramen ovale and eustachian
      valve in the causes of sudden deaths are reviewed.

PMID- 16442334
TI  - Adult stature reconstruction from the calcaneus of South Africans of European
      descent.
AB  - The reconstruction of adult stature from length of limb bones is not a new
      concept. Population specific regression equations for stature estimation have
      been derived from these bones in most part of the world. Due to increased
      violence in major cities of the world resulting in dismemberment of the human
      body and skeleton, there was a need for derivation of regression equations from
      fragments of long bones of limbs and segments of the vertebral column. This was
      achieved with lower accuracies compared to intact limb bones. The calcaneus, the
      largest of the foot bones, has been used for sex determination in Americans,
      Europeans and South Africans. Its usefulness in the estimation of stature is not
      well documented. In this study, Fully's anatomical method was utilized in the
      estimation of stature of 85 complete skeletons of South Africans of European
      descent of known sex and age, obtained from the Raymond A Dart Collection of
      Human skeletons. Univariate and multivariate regression equations were derived
      from nine measurements of the calcaneus. Most measurements presented with
      significantly positive correlation with stature. The resulting standard error of
      estimate, which is a measure of the accuracy of the equations, compared well with
      the values that have been recorded for fragments of long bones; thereby making
      the calcaneus a reliable skeletal element in the estimation of adult stature of
      South Africans of European descent.

PMID- 16442336
TI  - The forensic pathology initiative from Home Office pathologist to home-office
      pathologist?

PMID- 16442335
TI  - An unusual case of suicidal asphyxia by smothering.
AB  - A case is presented of a 30-year-old man suffering from borderline personality
      disorder who committed suicide by means of smothering. He was hospitalized at the
      psychiatric department of a public hospital for several months and was found dead
      in the seclusion room. The death resulted from an obstruction of the upper
      aerodigestive tract after ingurgitation of pellets of toilet paper. A literature
      review revealed several cases of suicidal asphyxia by smothering of patients with
      a history of psychiatric illness. Our patient's operating process had not been
      reported before to our knowledge.

PMID- 16442337
TI  - The fatal case of a cocaine body-stuffer and a literature review - towards
      evidence based management.
AB  - The case of a 50-year old female body-stuffer who collapsed and died more than
      10h after swallowing a plastic wrap of cocaine is reported. The case is discussed
      together with a review of the literature in order that guidelines on managing
      body-stuffers in police custody can be evidence based.

PMID- 16442338
TI  - Overview of the ossified stylohyoid ligament based in more than 1200 forensic
      autopsies.
AB  - The human stylohyoid chain presents considerable anatomic variability. In a
      personal series of 1215 forensic autopsies, eleven cases of complete ossification
      of the stylohyoid ligament have been revealed. Nine cases were bilateral and two
      cases were unilateral ossifications. A fractured ossified stylohyoid ligament was
      found in one case. The embryology and clinical significance of this condition has
      been mentioned briefly.

PMID- 16442339
TI  - The changing face of voluntary welfare provision in New Zealand.
AB  - This paper contributes a micro-level analysis of voluntary welfare providers, an
      under explored avenue of geographical research. It analyses the localised social
      impacts of the macroeconomic restructuring of the Welfare State in New Zealand in
      the 1980s and 1990s on the work of voluntary service organisations (VSOs) and
      drop-in centres (DICs) as spaces of care in Dunedin, a small South Island city.
      We document differences among VSOs and DICs in terms of funding, clientele, and
      adjustments to service provision to satisfy increasing numbers of patrons and the
      changing composition of demand. Our findings suggest policy recommendations
      which, we believe, would do much to enhance the ability of both DICs and smaller
      VSOs to meet client needs.

PMID- 16442341
TI  - Within-subject reliability of motor unit number estimates and quantitative motor
      unit analysis in a distal and proximal upper limb muscle.
AB  - OBJECTIVE: To establish within-subject reliability of motor unit number estimates
      (MUNEs) and quantitative MU analysis using decomposition-based quantitative
      electromyography (DQEMG). METHODS: Following the acquisition of a maximum M-wave,
      needle and surface-detected EMG signals were collected during contractions of the
      first dorsal interrosseous (FDI) and biceps brachii (BB). DQEMG was used to
      extract motor unit potential (MUP) trains and surface-detected MUPs associated
      with each train, the mean size of which was divided into the maximum M-wave to
      obtain a MUNE. Retests were performed following the initial test to evaluate
      reliability. RESULTS: Subjects test-retest MUNEs were highly correlated (r=0.72
      FDI; 0.97 BB) with no significant differences between test and retest MUNE values
      (P>0.10). Ninety-five percent confidence intervals were calculated to establish
      the range of expected retest MUNE variability and were +/-41 MUs for the FDI and
      BB. Quantitative information pertaining to MU size, complexity and firing rate
      were similar for both tests. CONCLUSION: MUNEs and quantitative MU data can be
      obtained reliably from the BB and FDI using DQEMG in individual subjects.
      SIGNIFICANCE: Establishing within-subject reliability of MUNEs and quantitative
      MU analysis allow clinicians to longitudinally follow changes in the MU pool of
      individuals with disorders of the central or peripheral nervous system in
      addition to assessing their response to treatments.

PMID- 16442340
TI  - Applications of dipeptidyl peptidase IV inhibitors in diabetes mellitus.
AB  - A number of alternative therapies for type 2 diabetes are currently under
      development that take advantage of the actions of the incretin hormones glucagon
      like peptide-1 and glucose-dependent insulinotropic polypeptide on the pancreatic
      beta-cell. One such approach is based on the inhibition of dipeptidyl peptidase
      IV (DP IV), the major enzyme responsible for degrading the incretins in vivo. DP
      IV exhibits characteristics that have allowed the development of specific
      inhibitors with proven efficacy in improving glucose tolerance in animal models
      of diabetes and type 2 human diabetics. While enhancement of insulin secretion,
      resulting from blockade of incretin degradation, has been proposed to be the
      major mode of inhibitor action, there is also evidence that inhibition of gastric
      emptying, reduction in glucagon secretion and important effects on beta-cell
      differentiation, mitogenesis and survival, by the incretins and other DP IV
      sensitive peptides, can potentially preserve beta-cell mass, and improve insulin
      secretory function and glucose handling in diabetics.

PMID- 16442342
TI  - Corticospinal tract conduction block results in the prolongation of central motor
      conduction time in compressive cervical myelopathy.
AB  - OBJECTIVE: The objective of this study was to analyze corticospinal function in
      patients with compressive cervical myelopathy and to elucidate the mechanism
      underlying its prolonged central motor conduction time (CMCT). METHODS: Motor
      evoked potentials following transcranial magnetic stimulation (TMS) and
      peripheral conduction time in the ulnar and tibial nerves following electrical
      stimulation were measured from the abductor digiti minimi (ADM) and abductor
      hallucis (AH) muscles in 24 patients with compressive cervical myelopathy and
      used to calculate CMCT. Spinal cord evoked potentials (SCEPs) following
      transcranial electric stimulation were recorded intraoperatively from the C2-3 to
      C6-7 intervertebral levels. Correlations between prolonged CMCT and SCEP values
      were then estimated. RESULTS: The shorter/longer CMCT between the patients' right
      and left ADM and AH were 8.5+/-2.9/11.5+/-3.3 and 16.2+/-3.1/18.4+/-3.3 ms,
      respectively (mean+/-SD). The SCEPs amplitude at C6-7, compared to C2-3, was
      25.7+/-21.0%. The attenuation of SCEP amplitude, but not latency, at C6-7
      correlated significantly with CMCT prolongation. CONCLUSIONS: Our data support
      the view that CMCT prolongation is primarily due to corticospinal conduction
      block, rather than conduction delay. SIGNIFICANCE: Insight was provided into the
      mechanism of corticospinal dysfunction in compressive cervical myelopathy.

PMID- 16442343
TI  - EEG in Creutzfeldt-Jakob disease.
AB  - Electroecenphalography (EEG) is an integral part of the diagnostic process in
      patients with Creutzfeldt-Jakob disease (CJD). The EEG has therefore been
      included in the World Health Organisation diagnostic classification criteria of
      CJD. In sporadic CJD (sCJD), the EEG exhibits characteristic changes depending on
      the stage of the disease, ranging from nonspecific findings such as diffuse
      slowing and frontal rhythmic delta activity (FIRDA) in early stages to disease
      typical periodic sharp wave complexes (PSWC) in middle and late stages to
      areactive coma traces or even alpha coma in preterminal EEG recordings. PSWC,
      either lateralized (in earlier stages) or generalized, occur in about two-thirds
      of patients with sCJD, with a positive predictive value of 95%. PSWC occur in
      patients with methionine homozygosity and methionine/valine heterozygosity but
      only rarely in patients with valine homozygosity at codon 129 of the prion
      protein gene. PSWC tend to disappear during sleep and may be attenuated by
      sedative medication and external stimulation. Seizures are an uncommon finding,
      occurring in less than 15% of patients with sCJD. In patients with iatrogenic
      CJD, PSWC usually present with more regional EEG findings corresponding to the
      site of inoculation of the transmissible agent. In genetic CJD, PSWC in its
      typical form are uncommon, occurring in about 10%. No PSWC occur in EEG
      recordings of patients with variant CJD.

PMID- 16442344
TI  - Proximal conduction abnormality of the facial nerve in Miller Fisher syndrome: a
      study using transcranial magnetic stimulation.
AB  - OBJECTIVE: To investigate facial nerve conduction, including its proximal
      segment, in Miller Fisher syndrome. METHODS: Three patients underwent facial
      nerve conduction studies comprising stylomastoid electrical stimulation and
      transcranial magnetic stimulation at the entrance of the facial canal within the
      skull and of the cortical representation area. All 3 patients presented with
      acute bilateral complete ophthalmoplegia, areflexia, mild ataxia and varying
      other symptoms. One of the patients had bilateral facial palsy; the other two had
      normal facial innervation. RESULTS: Findings suggestive of demyelination of the
      proximal segment of the facial nerve were observed in each of the 3 patients with
      Miller Fisher syndrome. The patient with bilateral facial palsy had absent
      responses to canalicular stimulation on both sides, while the other two showed
      increased temporal dispersion and prolonged latency in the proximal nerve
      segments. CONCLUSIONS: Our findings suggest that the primary pathology of facial
      nerve lesion in Miller Fisher syndrome is demyelination and that it is localized
      to the proximal nerve segment. This is in line with the known vulnerability of
      proximal nerve segments (spinal roots) in other dysimmune demyelinating
      polyneuropathies. SIGNIFICANCE: Facial nerve conduction study with magnetic
      stimulation can localize and detect even subclinical facial nerve dysfunction in
      patients with Miller Fisher syndrome. The technique may contribute to the
      diagnosis of this disease, where electrophysiologic findings are scanty.

PMID- 16442345
TI  - Origin, structure, and role of background EEG activity. Part 4: Neural frame
      simulation.
AB  - OBJECTIVE: To develop a method for simulating background EEG based on the premise
      that the self-organized activity from synaptic interaction among populations of
      neurons creates sustained fluctuations that can be modeled with the filtered
      output of a random number generator. METHODS: The logarithm of the amplitude of
      activity was weighted in accordance with 1/f, the log frequency in both temporal
      (PSD(T)) and spatial (PSD(X)) power spectral densities. The activity was
      spatially smoothed by volume conduction. Further deviation from full randomness
      was by sustained spatial coherence averaging 25% of total power. The departure
      from the background state to an active state, as seen in the awake EEG, was
      simulated by adding segments that were 90% correlated while attenuating by 50%
      the uncorrelated background activity in those segments. Spatial amplitude
      modulation was imposed on the correlated noise to create signals that simulated
      AM patterns. RESULTS: The statistical properties of the EEG that were replicated
      (Freeman, 2004a,b, 2005) included the PSD(T), PSD(X), point spread function
      (PSF), partitioning of the variance with PCA, and the percentages of correct
      classification of AM patterns. CONCLUSIONS: The origin of background EEG was
      traced to self-sustaining mutual excitation among pyramidal cells creating stable
      noise that was filtered by self-organized criticality to give 1/f(2) PSD, by
      inhibitory feedback to give oscillations in the classic clinical bands, and by
      volume conduction to give smoothing. The essential change that identified a frame
      in EEG was transient synchrony by phase transition among cortical populations in
      beta and gamma bands of the PSD(T). SIGNIFICANCE: This simulation can provide
      test data with which to optimize techniques for noninvasively extracting
      information from the EEG for diagnosis and treatment evaluation of
      neuropsychiatric disorders and for operation by paraplegics of prosthetic
      devices.

PMID- 16442346
TI  - The effects of memory load and stimulus relevance on the EEG during a visual
      selective memory search task: an ERP and ERD/ERS study.
AB  - OBJECTIVE: Psychophysiological correlates of selective attention and working
      memory were investigated in a group of 18 healthy children using a visually
      presented selective memory search task. METHODS: Subjects had to memorize one
      (load1) or 3 (load3) letters (memory set) and search for these among a
      recognition set consisting of 4 letters only if the letters appeared in the
      correct (relevant) color. Event-related potentials (ERPs) as well as alpha and
      theta event-related synchronization and desynchronization (ERD/ERS) were derived
      from the EEG that was recorded during the task. RESULTS: In the ERP to the memory
      set, a prolonged load-related positivity was found. In response to the
      recognition set, effects of relevance were manifested in an early frontal
      positivity and a later frontal negativity. Effects of load were found in a search
      related negativity within the attended category and a suppression of the P3
      amplitude. Theta ERS was most pronounced for the most difficult task condition
      during the recognition set, whereas alpha ERD showed a load-effect only during
      memorization. CONCLUSIONS: The manipulation of stimulus relevance and memory load
      affected both ERP components and ERD/ERS. SIGNIFICANCE: The present paradigm may
      supply a useful method for studying processes of selective attention and working
      memory and can be used to examine group differences between healthy controls and
      children showing psychopathology.

PMID- 16442347
TI  - Gammadelta T cells: an alternative type of professional APC.
AB  - A subtype of activated human gammadelta T cells, termed Vdelta2+ T cells, has
      antigen-presentation features similar in potency and efficacy to those seen in
      dendritic cells. Comparable treatment of alphabeta T cells does not result in
      'professional' antigen presenting cells (APCs). What is so special about Vdelta2+
      T cells? How do they acquire these unexpected properties? Under what
      physiological conditions would such a bridge between innate and adaptive immunity
      come into play? In addition to discussing these questions, we introduce a model
      that correlates the expression of lymph node homing receptors in Vdelta2+ T cells
      with the involvement of this alternative type of APC in anti-microbial alphabeta
      T cell responses.

PMID- 16442348
TI  - Bothrops moojeni myotoxin-II, a Lys49-phospholipase A2 homologue: an example of
      function versatility of snake venom proteins.
AB  - MjTX-II, a myotoxic phospholipase A(2) (PLA(2)) homologue from Bothrops moojeni
      venom, was functionally and structurally characterized. The MjTX-II
      characterization included: (i) functional characterization (antitumoral,
      antimicrobial and antiparasitic effects); (ii) effects of structural
      modifications by 4-bromophenacyl bromide (BPB), cyanogen bromide (CNBr), acetic
      anhydride and 2-nitrobenzenesulphonyl fluoride (NBSF); (iii) enzymatic
      characterization: inhibition by low molecular weight heparin and EDTA; and (iv)
      molecular characterization: cDNA sequence and molecular structure prediction. The
      results demonstrated that MjTX-II displayed antimicrobial activity by growth
      inhibition against Escherichia coli and Candida albicans, antitumoral activity
      against Erlich ascitic tumor (EAT), human breast adenocarcinoma (SK-BR-3) and
      human T leukemia cells (JURKAT) and antiparasitic effects against Schistosoma
      mansoni and Leishmania spp., which makes MjTX-II a promising molecular model for
      future therapeutic applications, as well as other multifunctional homologous
      Lys49-PLA(2)s or even derived peptides. This work provides useful insights into
      the structural determinants of the action of Lys49-PLA(2) homologues and,
      together with additional strategies, supports the concept of the presence of
      others "bioactive sites" distinct from the catalytic site in snake venom myotoxic
      PLA(2)s.

PMID- 16442350
TI  - Determination of ranitidine in urine by capillary electrophoresis
      electrochemiluminescent detection.
AB  - The fast analysis of ranitidine is of clinical importance in understanding its
      efficiency and a patient's treatment history. In this paper, a novel
      determination method for ranitidine based on capillary electrophoresis
      electrochemiluminescence detection is described. The conditions affecting
      separation and detection were investigated in detail. End-column detection of
      ranitidine in 5 mM Ru(bpy)(3)(2+) solution at applied voltage of 1.20 V was
      performed. Favorable ECL intensity with higher column efficiency was achieved by
      electrokinetic injection for 10s at 10 kV. The R.S.D. values of ECL intensity and
      migration time were 6.38 and 1.84% for 10(-4) M and 6.01 and 0.60% for 10(-5) M,
      respectively. A detection limit of 7 x 10(-8) M (S/N=3) was achieved. The
      proposed method was applied satisfactorily to the determination of ranitidine in
      urine in 6 min.

PMID- 16442349
TI  - Inhibition of protein tyrosin phosphatase improves vascular endothelial
      dysfunction.
AB  - The study has been designed to investigate the effect of Bis-(maltolato)
      oxovanadium (BMOV), an inhibitor of protein tyrosin phosphatase (PTPase), in
      diabetes mellitus and hyperhomocysteinemia induced vascular endothelial
      dysfunction. Streptozotocin (55 mg kg(-1), i.v.) and methionine (1.7% w/w, p.o.,
      4 weeks) were administered to rats to produce diabetes mellitus (serum glucose
      >140 mg dl(-1)) and hyperhomocysteinemia (serum homocysteine>10 microM),
      respectively. Vascular endothelial dysfunction was assessed using isolated aortic
      ring preparation, electron microscopy of thoracic aorta and serum concentration
      of nitrite/nitrate. Serum thiobarbituric acid reactive substances (TBARS) were
      estimated to assess oxidative stress. Atorvastatin has been employed in the
      present study as standard drug to improve vascular endothelial dysfunction. BMOV
      (0.2 mg/ml in drinking water) or atorvastatin (30 mg kg(-1), p.o.) in diabetic
      and hyperhomocysteinemic rats significantly reduced serum glucose and
      homocysteine concentration. BMOV or atorvastatin markedly improved acetylcholine
      induced endothelium dependent relaxation, vascular endothelial lining, serum
      nitrite/nitrate concentration and serum TBARS in diabetic and
      hyperhomocysteinemic rats. However, this ameliorative effect of BMOV has been
      prevented by l-NAME (25 mg kg(-1), i.p.), an inhibitor of NOS or by glibenclamide
      (5 mg kg(-1), i.p.), a blocker of ATP sensitive K(+) channels. Therefore, it may
      be concluded that BMOV induced inhibition of PTPase may activate eNOS due to
      opening of ATP sensitive K(+) channels and consequently reduce oxidative stress
      to improve vascular endothelial dysfunction.

PMID- 16442351
TI  - Validation of the measurement of low concentrations of 5-hydroxytryptamine in
      plasma using high performance liquid chromatography.
AB  - A sensitive and rapid assay is described for the measurement of low
      concentrations of 5-hydroxytryptamine (5-HT) present in human platelet-depleted
      plasma (PDP) using reverse-phase high performance liquid chromatography (HPLC)
      with fluorimetric detection. With an analysis time of 12 min, this method is
      particularly useful for large-scale clinical trials investigating small
      differences in PDP 5-HT concentrations in conditions such as functional
      gastrointestinal disorders (FGID). The limit of detection and quantification were
      1 and 3 nmol/l, respectively, and the calibration curve linear between 1 and 1000
      nmol/l. The within-day and between-day precision were 4.3 and <13.6%,
      respectively.

PMID- 16442353
TI  - Assay of ochratoxin A in grape by high-pressure liquid chromatography coupled on
      line with an ESI-mass spectrometry.
AB  - In this paper, we propose a method for detection of ochratoxin A (OTA) in grapes
      by using nano-reversed-phase high-performance liquid chromatography-electrospray
      ionization-mass spectrometry (nano-RP-HPLC-ESI-MS). The method is rapid, highly
      sensitive and reproducible. OTA is extracted preferably from the entire acinus,
      rather than must; using chloroform at long incubation time period, lyophilized,
      resolubilized in acetonitrile (AcCN) and injected onto a reversed phase capillary
      or analytical column. Capillary columns are the method of choice because it
      requires a reduced amount of injected sample and consequently the chloroform
      necessary for OTA extraction, which is a toxic agent. This method gives a
      detection limit of femtog/ml, without resorting to an immunoaffinity clean-up or
      concentration, which makes it by far superior to any other method reported.
      Moreover, by using MS as a detection method it is possible, in the case of a
      complex matrix, to measure its molecular mass and to confirm the presence of OTA
      by MS-MS, which cannot be done by fluorescent detection. The method has a high
      sample extraction throughput (24/h) and has adequate precision (between batch
      C.V. <8%) and sensitivity (limit of detection (LOD)=1 pg/g; limits of
      quantification (LOQ)=2 pg/g) for OTA measured.

PMID- 16442352
TI  - Detection of sulphamethazine residues in cattle and pig hair by HPLC-DAD.
AB  - An HPLC method with diode array detection (DAD) is proposed for the detection of
      sulphamethazine (SMZ) residues in pig and cattle hair. Hair samples were
      extracted under alkaline conditions (NH4OH 0.2M for calf samples and NaOH 0.1M
      for piglet samples) and purified with a dual solid-phase extraction (SPE)
      cartridge system (reverse phase/strong-cation exchange). Recovery of SMZ in
      fortified samples varied from 70 to 85%, with a limit of quantification of 0.155
      ng/mg. Residues of SMZ (7.2-59.2 ng/mg) were detected both in calf and piglet
      hairs after a therapeutic treatment with SMZ, while no interfering peak was
      observed in samples from untreated animals.

PMID- 16442354
TI  - Association between time of statin initiation after hospital discharge from acute
      myocardial infarction and risk of recurrence and mortality in patients > or =65
      years of age.
AB  - Clinical studies have shown the benefit of statin use after acute myocardial
      infarction (AMI). However, it is uncertain how this benefit relates to the timing
      of statin initiation after AMI. We created a retrospective cohort (from 1996 to
      2001) using health care databases in Quebec, Canada, to study patients (> or =65
      years of age) who had AMI and differed in time of statin initiation within the
      first 90 days after discharge. Rates of recurrent AMI and mortality were compared
      between patients who initiated statins at discharge (early group) and those who
      initiated statins 1 month later and up to 90 days after discharge (delayed
      group). A multivariate Cox's regression model was used in the comparison. We used
      prescription time distribution matching to control for survival difference
      between groups. The early and delayed groups consisted of 3,075 and 1,187
      patients, respectively. During the 1-year follow-up, there was no evidence to
      suggest a difference in outcome between groups. Adjusted hazard ratios for early
      versus delayed initiation were 1.03 (95% confidence interval 0.56 to 1.87) at 3
      months and 1.24 (95% confidence interval 0.96 to 1.62) at 1 year. Analyses that
      were restricted to first-time statin users or excluded patients who had severe co
      morbidity or were > or =85 years old did not change the results. Our findings
      were not affected by changing the definition of delayed use within the 90-day
      period. In conclusion, delay of statin initiation up to 30 to 90 days after
      discharge after AMI does not appear to lead to a difference in the rates of
      recurrent AMI and mortality compared with statin initiation at discharge.

PMID- 16442355
TI  - Comparison of usefulness of left ventricular diastolic versus systolic function
      as a predictor of outcome following primary percutaneous coronary angioplasty for
      acute myocardial infarction.
AB  - Left ventricular (LV) diastolic function is an important predictor of morbidity
      and mortality after acute myocardial infarction (AMI). We evaluated the role of
      diastolic function in predicting in-hospital events and LV ejection fraction (EF)
      6 months after a first AMI that was treated with primary percutaneous coronary
      intervention (PCI). We prospectively enrolled 59 consecutive patients who were 60
      +/- 15 years of age (48 men), presented at our institution with their first AMI,
      and were treated with primary PCI. Patients underwent 2-dimensional and Doppler
      echocardiography, including tissue Doppler imaging of 6 basal mitral annular
      regions within 24 hours after primary PCI and were followed until discharge.
      Clinical and echocardiographic variables at index AMI were compared with a
      combined end point of cardiac death, ventricular tachycardia, congestive heart
      failure, or emergency in-hospital surgical revascularization. Follow-up
      echocardiographic assessment was performed at 6 months in 24 patients. During
      hospitalization, 3 patients died, 7 developed congestive heart failure, 4 had
      ventricular tachycardia, and 1 required emergency surgical revascularization.
      Stepwise logistic regression analysis showed the ratio of early mitral inflow
      diastolic filling wave (E) to peak early diastolic velocity of non-infarct
      related mitral annulus (p < 0.01) (E') and mitral inflow E-wave deceleration time
      (p < 0.02) to be independent predictors of in-hospital cardiac events
      (generalized R2 = 0.66). In a stepwise multiple linear regression model,
      independent predictors of follow-up LVEF were mitral inflow deceleration time (R2
      = 0.39, p = 0.002), baseline LVEF (R2 = 0.54, p < 0.02), and mitral inflow peak
      early velocity/mitral annular peak early velocity (or E/E') of infarct annulus
      (R2 = 0.66, p = 0.02). In conclusion, in patients who are treated with primary
      PCI for a first AMI, E/E' velocity ratio and mitral inflow E-wave deceleration
      time are strong predictors of in-hospital cardiac events and of LVEF at 6-month
      follow-up.

PMID- 16442356
TI  - Usefulness of biomarkers for predicting long-term mortality in patients with
      diabetes mellitus and non-ST-elevation acute coronary syndromes (a GUSTO IV
      substudy).
AB  - The present study evaluated whether biomarkers of ischemia, inflammation,
      myocardial damage, and dysfunction are equally useful in patients who have
      diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute
      coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who
      had non-ST-elevation ACS and were included in the Fourth Global Utilization of
      Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro
      B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and
      interleukin-6 were analyzed in serum samples that were obtained at a median of
      9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients
      who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The
      median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas
      troponin T levels did not differ by DM status. Mortality increased with ascending
      quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the
      bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses,
      factors that were predictive of 1-year mortality in patients who did not have DM
      were also significant for those who did. Presence of ST depression > 0.5 mm had
      the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP
      levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and
      interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to
      3.0) were significant biomarker predictors. In conclusion, DM confers a high long
      term mortality in non-ST-elevation ACS. Despite a larger proportion of ST
      depression and increased levels of NT-pro-BNP and interleukin-6 at admission,
      these factors provide independent prognostic information that may improve risk
      stratification and guidance of treatment.

PMID- 16442357
TI  - Comparison of accuracy of 64-slice cardiovascular computed tomography with
      coronary angiography in patients with suspected coronary artery disease.
AB  - Cardiovascular computed tomography (CVCT) with the recently released 64-slice
      technology increases spatial resolution and decreases acquisition times and slice
      thickness. We investigated the accuracy of 64-slice CVCT in relation to catheter
      angiography. We studied 66 sequential subjects who underwent 64-slice CVCT and
      catheter angiography within 30 days. Accuracy results were 94% for interpretable
      images, 95% for sensitivity, 96% for specificity, 97% for positive predictive
      value, and 92% for negative predictive value for lesions with >50% stenosis. We
      found 100% agreement between 64-slice CVCT and catheterization among vein graft
      evaluations (9 of 9). These metrics are vastly improved from the 16-slice
      generation and support 64-slice CVCT as a reliable diagnostic tool.

PMID- 16442358
TI  - Comparison of levels of serum matrix metalloproteinase-9 in patients with acute
      myocardial infarction versus unstable angina pectoris versus stable angina
      pectoris.
AB  - Matrix metalloproteinases (MMPs) are important for resorption of extracellular
      matrixes and may degrade the fibrous cap of an atherosclerotic plaque, thus
      contributing to coronary plaque rupture. Histologic studies have shown MMP
      expression in lesions of acute coronary syndrome. In this study, we evaluated the
      relation between plaque morphology as obtained by intravascular ultrasound before
      percutaneous coronary intervention and serum MMP levels in patients who had
      coronary artery disease. We enrolled consecutive 47 patients who had acute
      myocardial infarction (AMI), 23 who had unstable angina pectoris (UAP), and 19
      who had stable effort angina pectoris and underwent intravascular ultrasound
      before percutaneous coronary intervention followed by successful primary
      percutaneous coronary intervention. Peripheral blood was obtained from all
      patients before angiography and serum levels of MMP-1,-2, and -9 were analyzed.
      Serum levels of MMP-9 in the AMI and UAP groups were significantly higher than
      that in the stable effort angina pectoris group (p = 0.007 and 0.04,
      respectively). From the intravascular ultrasound findings before percutaneous
      coronary intervention, plaque rupture was detected in 26 patients (55%) in the
      AMI group and in 11 patients (48%) in the UAP group. In these 2 groups, patients
      with plaque rupture had significantly higher levels of MMP-9 than patients who
      did not have plaque rupture (p = 0.03 and 0.01, respectively). Multiple logistic
      regression analysis showed that MMP-9 was the only independent predictor of
      plaque rupture (p = 0.004). In conclusion, high levels of MMP-9 in patients who
      have AMI and UAP are related to the presence of plaque rupture in the culprit
      lesion.

PMID- 16442359
TI  - Association between the ankle-brachial index and future coronary calcium (the
      Rancho Bernardo study).
AB  - This study investigated whether the ankle-brachial index (ABI) is associated with
      coronary artery calcium (CAC) in a cohort of men and women who were free of
      clinical coronary heart disease. CAC was assessed by electron beam computed
      tomography in 279 community-based subjects who also had ABI measurements 7 years
      previously. Patients' mean age was 65.8 years and 51.3% were women. Thirty-three
      patients (11.8%) had an ABI < 1.0, 11 (3.9%) had an ABI < 0.9, and 4 (1.4%) had
      an ABI < 0.8. Prevalences of any CAC were 70% for women and 95% for men. In men
      and women, there was a U-shaped relation between CAC and ABI category, with the
      lowest CAC score being in the interval from 1.0 to 1.09. On multivariable
      analysis, women whose ABI was < 1.0 had a 2.7-fold higher risk (p = 0.03) for
      increasing amounts of CAC. Men whose ABI was below this same cutpoint had a
      similar but nonsignificant increase in risk (odds ratio 2.1, p = 0.1). In
      conclusion, ABI was significantly associated with the presence and extent of
      future CAC measured 7 years later.

PMID- 16442360
TI  - Early outcome of treatment of ostial de novo left anterior descending coronary
      artery lesions with drug-eluting stents.
AB  - We investigated early and mid-term clinical and angiographic outcomes of patients
      who had de novo ostial left anterior descending coronary artery (LAD) lesions
      that were treated with drug-eluting stents (DESs) or bare metal stents (BMSs). We
      identified 43 consecutive patients who underwent percutaneous intervention for
      isolated de novo ostial LAD lesions with implantation of DESs and compared them
      with 43 patients who had similar lesions that were treated with BMSs. All stents
      were successfully implanted. There were no significant differences with respect
      to major in-hospital complications between the 2 groups. One patient in the BMS
      group died during hospitalization. Non-Q-wave myocardial infarction occurred in 2
      patients (4.7%) in the DES and in 1 patient (2.3%) in the BMS group. At 9-month
      follow-up, 3 patients (7%) in the DES group and 11 (25.6%) in the BMS group
      underwent target lesion revascularization (p = 0.038); major adverse cardiac
      events were less frequent in the DES than in the BMS group (9.3% vs 32.6%, p =
      0.015). Angiographic follow-up was available in 82% of patients in the DES group
      and 75% of those in the BMS group (p = 0.6) and showed lower binary restenotic
      rates (5.7% vs 31.3%, p = 0.01) and smaller late loss (0.30 +/- 0.81 vs 1.23 +/-
      0.93 mm, p = 0.0001) in the DES group. In conclusion, DES implantation in de novo
      ostial LAD lesions appears safe and effective and is associated with a
      significant decrease in restenotic rates compared with historical experience with
      BMSs.

PMID- 16442361
TI  - Impact of clopidogrel on suppression of circulating levels of soluble CD40 ligand
      in patients with unstable angina undergoing coronary stenting.
AB  - This study investigated whether a regimen that comprised a loading dose of 300 mg
      of clopidogrel followed by 75 mg/day could significantly suppress circulating
      levels of soluble CD40 ligand (sCD40L) in patients who had unstable angina and
      underwent coronary stenting. Study results showed that the clopidogrel loading
      dose substantially decreased the circulating level of sCD40L at 24 hours after
      stenting (p <0.0001). Combined with aspirin, 75 mg/day of clopidogrel
      continuously decreased sCD40L levels after coronary stenting.

PMID- 16442362
TI  - Circadian variation in symptomatic subacute stent thrombosis after bare metal
      coronary stent implantation.
AB  - The present study examined whether onset of symptomatic subacute stent thrombosis
      (SAT) varies in a circadian manner after bare metal coronary stent implantation.
      Among 2,305 patients who underwent bare metal coronary stent implantation, 21
      (0.9%) developed symptomatic SAT. Results of the present study indicate that
      onset of symptomatic SAT is more frequent between 6:00 A.M. and 12:00 P.M. than
      at any other measured 6-hour period during the day.

PMID- 16442363
TI  - Usefulness of preprocedural soluble CD40 ligand for predicting restenosis after
      percutaneous coronary intervention in patients with stable coronary artery
      disease.
AB  - CD40-CD40 ligand interaction is involved in the inflammatory pathogenesis of
      atherosclerosis but clinical data about its role in stent restenosis are still
      limited. We investigated the effect of preprocedural CD40 ligand (sCD40L) on
      stent restenosis. We enrolled 36 patients (mean age 61.4 +/- 8.5 years) with
      stable angina who underwent successful stent implantation. Control angiograms
      were performed in all patients after 6 months. Plasma sCD40L and high-sensitive C
      reactive protein levels were measured before stent implantation and at 1 and 6
      months after the procedure. Angiographically proven restenosis rate was 27.8%.
      Plasma sCD40L levels were significantly higher (preprocedural 0.74 +/- 0.79) and
      more prolonged in patients with stent restenosis compared with patients without
      stent restenosis (0.02 +/- 0.22 ng/ml, p < 0.001). According to receiver-operator
      characteristic analysis, sCD40L > 0.41 ng/ml was the best distinguished parameter
      between patients with and without restenosis. At the multivariate logistic
      regression analysis, preprocedural sCD40L was an independent predictor (RR 39.4,
      95% confidence interval 4.05 to 383.8, p = 0.002) of stent restenosis after
      adjusting for confounding variables, including diabetes, reference vessel
      diameter, lesion length, stent diameter, stent length, and baseline high
      sensitive C-reactive protein. Sensitivity, specificity, and positive and negative
      predictive values and likelihood ratio of preprocedural sCD40L levels in stent
      restenosis were 78%, 92%, 78%, 92%, and 9.37%, respectively. In conclusion,
      enhanced inflammation of plaque (increased sCD40L) before percutaneous coronary
      intervention may increase the rate of stent restenosis. Increased preprocedural
      sCD40L level is an independent predictor of stent restenosis. We can use this
      marker for the assessment of risk stratification before planning stent
      implantation.

PMID- 16442364
TI  - Intravascular ultrasound characterization of the "black hole" phenomenon after
      drug-eluting stent implantation.
AB  - An intraluminal echolucent tissue, dubbed "black hole," has been identified by
      intravascular ultrasonography after intracoronary brachytherapy. This study
      reports the characteristics and incidence of the black hole in patients treated
      with drug-eluting stent implantation using a sirolimus-eluting stent (SES). We
      included intravascular ultrasound data from the Compassionate Use of Sirolimus
      Eluting Stent (SECURE, n = 61 lesions) registry, a study involving patients in
      whom previous brachytherapy had failed, and the DIABETES trial (n = 165 lesions),
      a multicenter, randomized study comparing SES versus bare metal stents in
      diabetic patients. Intravascular ultrasound follow-up was scheduled at 8 months
      (SECURE trial, post-brachytherapy population) and 9 months (DIABETES trial). In
      the SECURE population, a black hole was observed in 10 patients (19.6%). Seven
      black hole segments had significant intimal hyperplasia (> 10%). A black hole
      accounted for 27% of total intraluminal tissue. In the DIABETES trial, 2 patients
      (2.5%) in the SES group and none in the bare metal stent group showed echolucent
      intimal hyperplasia. In conclusion, a black hole occurred frequently after
      implantation of a SES in patients in whom intracoronary brachytherapy had
      previously failed. Black holes were also identified in a nonirradiated
      population, although the incidence was lower than in the post-brachytherapy
      patients. Bare metal stents were not associated with this phenomenon.

PMID- 16442365
TI  - Usefulness of exercise myocardial scintigraphy in multivessel coronary disease
      after incomplete revascularization with coronary stenting.
AB  - The aim of this prospective study was to evaluate the prognostic value of
      exercise myocardial scintigraphy in patients who undergo incomplete
      revascularization with percutaneous coronary stenting. In 322 consecutive
      patients (mean age 61 +/- 10 years), exercise technetium-99m-tetrofosmin single
      photon emission computed tomography scintigraphy was prospectively performed 4 to
      6 months after an incomplete revascularization procedure. Follow-up lasted < or =
      84 months (median 33). Patients with normal findings were at low risk of cardiac
      events compared with patients with mildly abnormal and severely abnormal findings
      (yearly event rate 1.5% vs 5.1% and 8.5%, respectively, p < 0.01). A significant
      difference was observed in hard, soft, and composite event-free survival among
      patients with normal, mildly abnormal, and severely abnormal findings (p < 0.01,
      p < 0.03, and p < 0.01, respectively). Nuclear data provided significant
      incremental prognostic value for cardiac events compared with the clinical,
      angiographic, and exercise test findings. In conclusion, in patients with
      incomplete revascularization procedures, exercise myocardial scintigraphy
      provides significant independent information concerning the subsequent risk of
      cardiac events, with an annualized event rate of < 2% for patients with normal
      scan findings. Myocardial scintigraphy is able to provide incremental prognostic
      information after adjusting for clinical, angiographic, and exercise variables.

PMID- 16442366
TI  - Intake of tuna or other broiled or baked fish versus fried fish and cardiac
      structure, function, and hemodynamics.
AB  - Fish intake is associated with improved cardiovascular health, including a lower
      risk of arrhythmic death, atrial fibrillation, and heart failure. However, the
      physiologic effects that may produce these cardiovascular benefits are not well
      established. We investigated the cross-sectional associations between a usual
      dietary intake of fish during the previous year and cardiac structure, function,
      and hemodynamics as determined by physical examination and 2-dimensional,
      Doppler, and M-mode transthoracic echocardiography among 5,073 older adults
      enrolled in the Cardiovascular Health Study. On multivariate-adjusted analyses,
      consumption of tuna or other broiled or baked fish was associated with a lower
      heart rate (p < 0.001), lower systemic vascular resistance (p = 0.002), and
      greater stroke volume (p < 0.001). Tuna/other fish intake was also associated
      with a higher E/A ratio (p = 0.004), a measure of more normal diastolic function.
      In contrast, fried fish or fish sandwich (fish burger) intake was associated with
      left ventricular wall motion abnormalities (p = 0.02), a reduced ejection
      fraction (p < 0.001), lower cardiac output (p = 0.04), a trend toward a larger
      left ventricular diastolic dimension (p = 0.07), and higher systemic vascular
      resistance (p = 0.003). In conclusion, in this large population-based study, the
      intake of tuna or other broiled or baked fish was associated with improved
      cardiac hemodynamics, but fried fish intake was associated with structural
      abnormalities indicative of systolic dysfunction and potential coronary
      atherosclerosis. These findings suggest potential specific physiologic mechanisms
      that may, in part, account for the effects of fish intake on cardiovascular
      health.

PMID- 16442367
TI  - Striated muscle safety of ezetimibe/simvastatin (Vytorin).
AB  - Despite the excellent benefit/risk profile of statins, their use is limited by a
      dose-related risk of adverse events, particularly those related to muscle
      toxicity. Ezetimibe/simvastatin (Vytorin) is a cholesterol-lowering therapy that
      inhibits the intestinal absorption (ezetimibe) and synthesis (simvastatin) of
      cholesterol. This analysis compared the muscle safety profiles of
      ezetimibe/simvastatin and simvastatin monotherapy. We reviewed muscle-related
      adverse event (AE) data from 17 randomized, blinded clinical trials (13 base and
      4 extension studies), in which ezetimibe and simvastatin were either co
      administered as separate entities or given as a combination tablet to 4,558
      patients. The following AE categories were summarized: incidence of
      musculoskeletal or connective-tissue AEs (all and drug related); discontinuations
      due to musculoskeletal or connective-tissue AEs (all and drug related); incidence
      of AEs reported under the term "myalgia" (all and drug related); discontinuation
      due to myalgia (all and drug related); incidence of "myopathy" (all and drug
      related); increases in creatine kinase to 3 to < 5, 5 to < 10, and > or = 10
      times the upper limit of normal. For all AE categories examined, the incidence of
      muscle-related clinical and laboratory AEs or discontinuations due to muscle
      related AEs was no more common in patients taking ezetimibe/simvastatin than in
      those taking simvastatin alone. Thus, the clinical trial experience with
      ezetimibe/simvastatin suggests that ezetimibe does not enhance or aggravate the
      muscle effects of simvastatin.

PMID- 16442368
TI  - Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African
      American patients in a six-week trial.
AB  - The lipid-modifying effects of statin therapy in hypercholesterolemic African
      Americans have not been well characterized. This study compared the efficacy and
      safety of rosuvastatin and atorvastatin treatment for 6 weeks in
      hypercholesterolemic African-American adults. In the African American
      Rosuvastatin Investigation of Efficacy and Safety (ARIES) trial (4522US/0002),
      774 adult African-Americans with low-density lipoprotein cholesterol > or = 160
      and < or = 300 mg/dl and triglycerides < 400 mg/dl were randomized to receive
      open-label rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg for 6 weeks. At
      week 6, significantly greater reductions in low-density lipoprotein cholesterol,
      total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B
      concentrations, as well as lipoprotein and apolipoprotein ratios, were seen with
      rosuvastatin versus milligram-equivalent atorvastatin doses (analysis of variance
      with Bonferroni-adjusted critical p < 0.017 for all comparisons). Rosuvastatin 10
      mg also increased high-density lipoprotein cholesterol significantly more than
      atorvastatin 20 mg (p < 0.017). Although statistical comparisons were not
      performed, larger proportions of rosuvastatin-treated patients than atorvastatin
      treated patients achieved National Cholesterol Education Program Adult Treatment
      Panel III low-density lipoprotein cholesterol goals. The median high-sensitivity
      C-reactive protein levels were significantly reduced statistically from baseline
      with rosuvastatin 20 mg and atorvastatin 20 mg among all patients and with
      rosuvastatin 10 and 20 mg and atorvastatin 20 mg in those patients with a
      baseline C-reactive protein level > 2.0 mg/L. The 2 study medications were well
      tolerated during the 6-week study period. In conclusion, rosuvastatin 10 and 20
      mg improved the overall lipid profile of hypercholesterolemic African-Americans
      better than did milligram-equivalent doses of atorvastatin.

PMID- 16442369
TI  - Association of the metabolic syndrome and insulin resistance with silent
      myocardial ischemia in patients with type 2 diabetes mellitus.
AB  - Metabolic syndrome is associated with elevated morbidity and mortality for overt
      coronary artery disease (CAD). In diabetic patients, CAD is often silent. The
      relation between metabolic syndrome and silent CAD has never been studied. We
      investigated whether metabolic syndrome is associated with silent CAD in patients
      with type 2 diabetes mellitus. We evaluated the prevalence of metabolic syndrome
      in 169 patients with uncomplicated diabetes and angiographically verified silent
      CAD and in 158 diabetic patients without myocardial ischemia on exercise
      electrocardiography, 48-hours ambulatory electrocardiography, and stress
      echocardiography. The groups were comparable for gender, age, glycemic control,
      and diabetes duration. Metabolic syndrome was defined according to the National
      Cholesterol Education Program criteria. To estimate insulin resistance in
      patients treated with diet alone or oral agents (122 patients with CAD and 115
      patients without CAD), the Homeostasis Model Insulin-Resistance Assessment (HOMA)
      was used. The prevalence of metabolic syndrome (59.8% vs 44.3%, p = 0.005) and
      HOMA (5.4 +/- 2.1 vs 4.9 +/- 2.8, p = 0.044) were significantly higher in those
      with CAD than in those without CAD. Multiple logistic regression analysis showed
      that the metabolic syndrome was associated with silent CAD (odds ratio 2.44, 95%
      confidence interval 1.19 to 5.02, p = 0.015). Among patients on diet alone or
      oral agents, the HOMA was the strongest predictor of silent CAD (odds ratio
      10.16, 95% confidence interval 2.60 to 39.63, p < 0.001). In conclusion, our data
      have shown an independent association of metabolic syndrome and insulin
      resistance with silent CAD in patients with type 2 diabetes mellitus. Other
      studies are needed to establish whether metabolic syndrome and HOMA are reliable
      markers to identify diabetic patients for additional screening for silent CAD.

PMID- 16442370
TI  - Blood pressure stress reactivity and left ventricular mass in a random community
      sample of African-American and caucasian men and women.
AB  - Exaggerated blood pressure (BP) reactivity to stress may contribute to left
      ventricular (LV) hypertrophy, a major risk factor for cardiovascular morbidity.
      This study examined the extent to which BP responses to acute stress are
      associated with LV mass and relative wall thickness in a community sample of
      African-American and white men and women. BP was measured at rest and in response
      to 2 acute challenges (mental arithmetic and handgrip). Systolic BP at rest was
      positively associated with LV mass and relative wall thickness (p < 0.001). The
      associations between the responses to the stressors and LV mass were not
      significant. African-American and white men who exhibited high BP responses to
      the arithmetic stressor had greater relative wall thickness than those with low
      reactivity (p < 0.05). In conclusion, BP reactivity is not related to LV mass,
      but may be related to concentric remodeling.

PMID- 16442371
TI  - Effects of C-reactive protein and the third and fourth components of complement
      (C3 and C4) on incidence of atrial fibrillation.
AB  - Although C-reactive protein (CRP) is a major cardiovascular risk factor, its
      association with atrial fibrillation (AF) remains controversial. This study
      explored whether the CRP-related incidence of AF is modified by serum markers of
      inflammation in a population-based cohort with follow-up data. Serum CRP and 2
      components of the complement system (C3 and C4) were determined in 1,011 healthy
      patients (25 to 64 years old). The incidence of AF was compared between groups
      defined by levels of CRP, C3, and C4. The follow-up time was 4 years. A high
      complement level was defined as either C3 or C4 in the top quartile. High CRP was
      associated with high complement components. An increased CRP level was associated
      with an increased incidence of AF. The complement components modified these
      associations. After risk factor adjustment, those with high CRP and high
      complement components had a significantly higher risk of AF (relative risk 3.0,
      95% confidence interval 2.0 to 4.2) than those with normal CRP and low complement
      levels. In the absence of a high complement level, a high CRP level was not
      significantly associated with AF (relative risk 1.1, 95% confidence interval 1.0
      to 1.4). In conclusion, high CRP levels are associated with high serum levels of
      complement components. These proteins increase the CRP-related incidence of AF.
      In the absence of elevated complement components, no statistically confirmed
      association was found between a high CRP level and AF.

PMID- 16442372
TI  - Usefulness of B-type natriuretic peptide and C-reactive protein in predicting the
      presence or absence of left ventricular hypertrophy in patients with systemic
      hypertension.
AB  - The diagnosis of left ventricular (LV) hypertrophy, an independent predictor of
      death and cardiovascular events, is difficult without using echocardiography.
      This study tested the hypothesis whether C-reactive protein (CRP) and B-type
      natriuretic peptide (BNP) would be useful to exclude echocardiographic LV
      hypertrophy. Consecutive hypertensive outpatients were asked to participate.
      Exclusion criteria were overt heart failure, severe renal insufficiency or any
      other severe concomitant illness. A venous blood sample was taken to measure
      plasma CRP and BNP concentrations. Echocardiographic LV hypertrophy was defined
      as LV mass > or =125 g/m2 for men and > or =110 g/m2 for women. In total, 320
      patients were studied, and 37 patients (12%) had echocardiographic LV
      hypertrophy. Patients with LV hypertrophy were significantly older and had higher
      CRP and BNP concentrations and higher systolic blood pressure than those without
      LV hypertrophy. The optimal cut-off points for the diagnosis of LV hypertrophy
      were 35 pg/ml for BNP (sensitivity 73%, specificity 72%) and 2.5 mg/L for CRP
      (sensitivity 68%, specificity 59%). Only 1 of 123 patients with values of BNP and
      CRP less than the optimal cut-off point had echocardiographic LV hypertrophy,
      resulting in a high negative predictive value of 99% for the 2 blood tests
      combined to exclude LV hypertrophy. In conclusion, in hypertensive patients,
      echocardiographic LV hypertrophy can be excluded on the basis of a single blood
      sample for the determination of BNP and CRP.

PMID- 16442373
TI  - Comparison of management of four patients with idiopathic dilated cardiomyopathy
      in a disease management program versus by a primary care physician.
AB  - In a heart failure (HF) disease management program (DMP), 4 patients with
      advanced HF and low ejection fractions had near full recovery within 4 to 45
      months. When discharged to their primary care physicians, all 4 had severe
      symptom relapse and deterioration of their left ventricular function. Readmission
      to the HF DMP for a second time resulted in similar improvement in all
      parameters, as was seen the first time.

PMID- 16442374
TI  - Comparison of six-month outcomes and hospitalization rates in heart failure
      patients with and without preserved left ventricular ejection fraction and with
      and without intraventricular conduction defect.
AB  - Prolonged QRS duration (>120 ms), as a marker of ventricular dyssynchrony, is an
      independent predictor of mortality in systolic heart failure (HF). Little
      information exists about the characteristics of patients with preserved ejection
      fractions (EFs) and prolonged QRS (intraventricular conduction defects [IVCDs]).
      The electronic records of 334 consecutive patients hospitalized with acutely
      decompensated HF were reviewed. A significant number of patients hospitalized
      with decompensated HF had preserved EFs with IVCD. They had similar readmission
      and mortality rates compared with their systolic HF counterparts and higher rates
      compared with those with preserved EFs without IVCD. These findings and the
      resulting possible therapeutic interventions (resynchronization) need further
      analysis in a larger prospective cohort.

PMID- 16442375
TI  - Clinical versus echocardiographic parameters to assess response to cardiac
      resynchronization therapy.
AB  - Currently, a clear definition of response to cardiac resynchronization therapy
      (CRT) is still lacking, and clinical and echocardiographic end points are used.
      It is also unclear whether patients with clinical responses also improve in
      echocardiographic end points (and vice versa). To better understand and define
      response to CRT, the relation between improvement in clinical and
      echocardiographic parameters was evaluated in 144 patients.

PMID- 16442376
TI  - Acute predictors of subacute complete heart block after alcohol septal ablation
      for obstructive hypertrophic cardiomyopathy.
AB  - Acute and subacute complete heart block (CHB) are sequelae of alcohol septal
      ablation (ASA) for obstructive hypertrophic cardiomyopathy. Temporary pacemakers
      are routinely placed at the time of ASA, but there are no widely accepted
      guidelines for their management. This study examined acute predictors of subacute
      CHB in 52 consecutive ASA procedures in 48 patients without preexisting permanent
      pacemakers. Acute CHB occurred during 32 ASA procedures (62%), with the return of
      atrioventricular conduction on the day of ASA in all cases. New intraventricular
      conduction defects (IVCDs) were noted after 32 procedures (62%); in 9 of these,
      there was new first-degree atrioventricular block as well. CHB recurred
      subacutely 36 +/- 22 hours after 13 ASA procedures (25%). In 5 of these cases,
      there was absent or inconsistent ventricular escape rhythm. Subacute CHB did not
      occur in 9 cases without acute CHB during ASA or new IVCDs after ASA. Acute CHB
      during ASA, new IVCDs after ASA, and new first-degree atrioventricular block
      after ASA incrementally increased the risk for subacute CHB. In conclusion,
      patients with acute CHB during ASA or new IVCDs after ASA are at high risk for
      developing subacute CHB, sometimes without a reliable escape rhythm; these
      patients should therefore have temporary pacing support for > or = 48 hours after
      ASA or the last occurrence of CHB. Patients without acute CHB during ASA or new
      IVCDs after ASA are at low risk for subacute CHB.

PMID- 16442377
TI  - Usefulness of aortic root dimension in persons > or = 65 years of age in
      predicting heart failure, stroke, cardiovascular mortality, all-cause mortality
      and acute myocardial infarction (from the Cardiovascular Health Study).
AB  - Echocardiographic measures of left ventricular (LV) function and structure as
      well as left atrial size have been reported to predict adverse cardiovascular
      disease (CVD) outcomes. Although anatomic changes of the aortic root are likely
      to reflect effects of hypertension and atherosclerosis, few data are available on
      the predictive value of aortic root dimension (ARD) for outcome in free-living
      populations. The purpose of this investigation was to determine whether in a
      cohort of patients aged > or = 65 years ARD was associated with traditional
      coronary heart disease (CHD) risk factors and with 10-year incident CVD outcomes.
      In the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Health
      Study, 3,933 free-living black and white men and women > or = 65 years of age
      without prevalent CVD had 2-dimensional directed M-mode echocardiographic
      measurements of ARD as part of a comprehensive evaluation. ARD was associated
      with age and gender (greater in men) but not race. ARD was also positively
      associated with diastolic blood pressure, LV hypertrophy, major
      electrocardiographic abnormalities, and other echocardiographic measures,
      including LV mass, ventricular septal and posterior wall thickness, and LV
      dimension. After adjustment for other known risk factors, high ARD was associated
      with an increased risk for incident congestive heart failure (CHF) in men (hazard
      ratio for upper compared with all other quintiles 1.47, p = 0.014), stroke in men
      and women (hazard ratio 1.39 per cm, p = 0.015), CVD mortality in men and women
      (hazard ratio 1.48 per cm, p = 0.007), and total mortality in men and women
      taking antihypertensive medications (hazard ratio 1.46 per cm, p = 0.007), but
      not with incident myocardial infarction (MI) (hazard ratio 0.89, p = 0.39). In
      conclusion, in a cohort of patients aged > or = 65 years without clinical CVD at
      baseline, ARD was associated with several CHD risk factors and measures of
      subclinical disease and was predictive of incident CHF, stroke, CVD mortality,
      and all-cause mortality, but not of incident MI.

PMID- 16442378
TI  - Effects of extreme endurance running on cardiac autonomic nervous modulation in
      healthy trained subjects.
AB  - This study examined spectral components of heart rate variability (HRV) during
      endurance mountain running in 8 healthy trained subjects. The data showed that
      during this type of mountain running, all spectral components of HRV may severely
      decrease, particularly very-low-frequency and low-frequency (LF) power,
      suggesting extreme activation of the sympathetic nervous system. The physiologic
      response of the heart in this situation was the downregulation of the beta
      adrenergic receptors to protect myocardial function, with a subsequent increase
      in parasympathetic tone, reflected by an increase in high-frequency (HF) power
      and a decrease in the LF/HF ratio.

PMID- 16442379
TI  - Mortality and size of abdominal aortic aneurysm at long-term follow-up of
      patients not treated surgically and treated with and without statins.
AB  - Of 130 patients with abdominal aortic aneurysms (AAAs) not treated surgically, 75
      (58%) were treated with statins. The sizes of the AAAs were 4.6 +/- 0.6 cm at
      baseline and 4.5 +/- 0.6 cm at 23-month follow-up in patients treated with
      statins (p = NS) and 4.5 +/- 0.6 cm at baseline and 5.3 +/- 0.6 cm at 24-month
      follow-up in patients not treated with statins (p < 0.001). Four of 75 patients
      (5%) treated with statins died at 45-month follow-up, and 9 of 55 patients (16%)
      not treated with statins died at 44-month follow-up (p < 0.05).

PMID- 16442380
TI  - A new paradigm for post-cardiac event resistance exercise guidelines.
AB  - Existing guidelines for resistance exercise in cardiac rehabilitation are vague
      and/or overly restrictive, limiting the ability of cardiac rehabilitation
      programs to help patients achieve their desired levels of daily activity in a
      timely manner after cardiac events. This study examines the illogical nature of
      the existing guidelines in relation to the activities of daily living patients
      are expected or required to carry out during the period of cardiac rehabilitation
      and the existing recommendations for dynamic exercise in cardiac rehabilitation.
      An improved method is proposed for prescribing resistance exercise in cardiac
      rehabilitation. A tool is presented that stratifies the risk associated with each
      of 13 common resistance exercises for 3 cardiac rehabilitation diagnosis groups
      (myocardial infarction [MI], pacemaker or implantable cardioverter defibrillator
      implantation, and coronary artery bypass graft surgery) that, if used in
      conjunction with blood pressure and heart rate measurements, will safely
      facilitate more efficacious resistance training in cardiac rehabilitation
      patients. In conclusion, changing the approach to resistance exercise in cardiac
      rehabilitation will accelerate patients' return to their desired levels of daily
      activity, improving patient satisfaction and decreasing cardiac rehabilitation
      program attrition.

PMID- 16442381
TI  - Usefulness of multidetector computed tomography for noninvasive evaluation of
      coronary arteries in asymptomatic patients.
AB  - This editorial addresses the capabilities, limitations, and potential of
      multidetector computed tomography (MDCT) for the noninvasive evaluation of
      coronary arteries in asymptomatic patients. The quantification of coronary
      calcium with MDCT correlates highly with that obtained by electron-beam computed
      tomography, but to date, neither has the capability of assessing the distribution
      of various morphologic patterns of calcium and their relation to other "soft"
      plaque components. Although MDCT can assess the thickness of the atherosclerotic
      wall and can readily identify calcific deposits, further plaque characterization
      (e.g., lipid pools and fibrous tissue), a prerequisite for the identification of
      most vulnerable lesions, is not yet a workable reality, even with the 64-slice
      machines in their current configuration. The noninvasive identification by MDCT
      of plaque components subtending vulnerable lesions will require additional
      improvement in the primary instrumentation, the use of hybrid constructs (e.g.,
      with positron emission tomography and magnetic resonance imaging), the
      development of novel methods of post-acquisitional analysis to extract latent
      images of plaque components (e.g., signal analysis based on 3-dimensional
      wavelets), or the adaptation of molecular imaging techniques at the cell and gene
      levels to computed tomography. Such unique approaches may soon contribute a long
      list of additional parameters that could be evaluated on a noninvasive basis as
      predictors of acute coronary syndromes and overall patient vulnerability.

PMID- 16442383
TI  - Response to "rapid desensitization for patients with aspirin sensitivity".

PMID- 16442384
TI  - Comparison of ST-segment deviation to scintigraphically quantified myocardial
      ischemia during acute coronary occlusion induced by percutaneous transluminal
      coronary angioplasty.
AB  - This study compared ST-segment changes during acute coronary artery occlusion
      with measurements of ischemia by myocardial scintigraphy. Forty patients who were
      referred for elective prolonged percutaneous transluminal coronary angioplasty
      underwent 12-lead electrocardiographic recording before the procedure (baseline)
      and continuously during the entire balloon inflation (occlusion). For each
      patient, the summed ST-segment deviation was calculated as the maximal absolute
      difference, elevation or depression, between baseline and occlusion recordings in
      all 12 leads. Each patient underwent 2 myocardial scintigraphies, 1 with
      technetium-99m sestamibi injected during the balloon inflation and 1 on the
      following day as a control study. Ischemia that was induced by balloon occlusion
      was quantified in terms of extent and severity. Results for the entire study
      group showed that summed ST deviation correlated with extent (r = 0.59, p <
      0.0001) and severity (r = 0.61, p < 0.0001) of ischemia. The location of maximal
      ST deviation differed for the 3 arteries. For occlusion of the left anterior
      descending artery, maximal ST deviation was elevated in lead V3. For occlusion of
      the left circumflex artery, maximal ST deviation was depressed in lead V2.
      Occlusion of the right coronary artery caused ST elevation in lead III and ST
      depression in lead V2. In conclusion, this study demonstrated a significant
      correlation between summed ST deviation and myocardial ischemia during coronary
      occlusion that is induced by percutaneous transluminal coronary angioplasty.

PMID- 16442385
TI  - Relation of atherothrombosis burden and volume detected by intravascular
      ultrasound to angiographic no-reflow phenomenon during stent implantation in
      patients with acute myocardial infarction.
AB  - This study investigated the mechanism of occurrence of the no-reflow phenomenon
      during stent implantation in patients with acute myocardial infarction (AMI)
      using intravascular ultrasound (IVUS) with volumetric analysis. Of 70 patients
      with AMI who underwent IVUS-guided stent implantation within 24 hours of symptom
      onset, 12 developed decreased Thrombolysis In Myocardial Infarction flow grade
      during stent implantation and without subsequent restoration to Thrombolysis In
      Myocardial Infarction flow grade before stenting. External elastic membrane cross
      sectional area and maximum diameter at the culprit lesion as measured by IVUS
      before stent implantation were significantly larger in the no-reflow group (n =
      12) than in the normal reflow group (n = 58; 20.1 +/- 6.5 vs 16.4 +/- 4.3 mm2, p
      = 0.015 for cross-sectional area and 5.2 +/- 0.9 vs 4.8 +/- 0.6 mm, p = 0.049 for
      maximum diameter). Plaque volume, volumetric plaque burden (plaque
      volume/external elastic membrane volume), and change in plaque volume during
      stent implantation (plaque volume after vs before) were significantly greater in
      the no-reflow group than in the normal reflow group (239 +/- 142 vs 178 +/- 72
      mm3, p = 0.030; 0.76 +/- 0.07 vs 0.71 +/- 0.06, p = 0.010; and -46 +/- 63 vs -11
      +/- 37 mm3, p = 0.013, respectively). In conclusion, high atherothrombotic burden
      and decreased plaque volume as detected by IVUS may be risk factors for
      development of the no-reflow phenomenon during stent implantation in patients
      with AMI.

PMID- 16442386
TI  - Effects of thrombolysis during out-of-hospital cardiopulmonary resuscitation.
AB  - In this post hoc analysis, we assessed effects of thrombolysis during out-of
      hospital cardiopulmonary resuscitation. The original study was designed as a
      double-blinded, prospective, multicenter, randomized, controlled clinical trial.
      In this report, 1,219 patients were randomized, but 33 patients were excluded due
      to missing study drug codes. Thus, 1,186 patients were analyzed based on receipt
      (n = 99) versus nonreceipt (n = 1,087) of thrombolysis; the primary end point was
      hospital admission, and the secondary end point was hospital discharge. Patients
      who received thrombolysis versus those who did not were significantly younger
      (mean +/- SD 62.7 +/- 13.3 vs 66.5 +/- 14.3 years of age, p = 0.01) and more
      likely to have had an acute myocardial infarction (75.3% vs 54.6%, p < 0.01) or
      pulmonary embolism (20.2% vs 12.0%, p = 0.03) as the suspected underlying cause
      for cardiac arrest. In patients who underwent thrombolysis versus those who did
      not, cardiac arrest was more often witnessed (86.9% vs 77.5%, p = 0.03), initial
      ventricular fibrillation was more likely (59.6% vs 38.0%, p < 0.01), and a short
      estimated interval (0 to 5 minutes) between collapse and initiation of basic life
      support was more likely (51.3% vs 29.2%, p < 0.01). In patients who received
      thrombolysis, sodium bicarbonate (45.5% vs 33.0%, p = 0.01), lidocaine (32.3% vs
      18.1%, p < 0.01), and amiodarone (30.3% vs 12.2%, p < 0.01) were administered
      significantly more often. Hospital admission rates were significantly higher in
      patients who underwent thrombolysis than in patients who did not (45.5% vs 32.7%,
      p = 0.01), and there was a trend to higher hospital discharge rates (14.1% vs
      9.5%, p = 0.14). In patients who had suspected myocardial infarction, hospital
      admission and discharge rates were significantly higher in patients who underwent
      thrombolysis than in patients who did not. In logistic regression models after
      adjusting for confounding variables (e.g., age, initial electrocardiographic
      rhythm, and initiation of basic life support), hospital admission and discharge
      rates did not differ significantly. In conclusion, even when being employed in
      patients with a potentially better chance to survive, thrombolysis in patients
      with cardiac arrest resulted in an increased hospital admission but not discharge
      rate in this post hoc analysis.

PMID- 16442387
TI  - Comparison of mortality risk for electrocardiographic abnormalities in men and
      women with and without coronary heart disease (from the Cardiovascular Health
      Study).
AB  - Mortality risk associated with electrocardiographic (ECG) abnormalities has been
      commonly reported to be lower in women than in men. We compared coronary heart
      disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1
      year follow-up in 4,912 participants in the Cardiovascular Health Study who were
      > or = 65 years of age. The hypothesis was that mortality risk for ECG
      abnormalities is not lower in women than in men. Five ECG variables were
      significant mortality predictors in Cox regression models that were adjusted for
      demographic, clinical, and medication variables. Gender differences were
      significant and mortality risk was higher in women for ECG estimates of left
      ventricular mass for both end points and for nondipolar QRS voltage for all-cause
      mortality. When evaluated simultaneously in multiple ECG variable risk models in
      subgroups that were stratified by baseline CHD status, no gender difference was
      significant. In the latter models, ST depression was a strong predictor of CHD
      mortality in groups with and without previous CHD. Other significant ECG
      predictors were previous myocardial infarction in the previous CHD group and
      nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were
      significant predictors of all-cause mortality in the CHD-free group, with risk
      increases of 18% to 50%. The risk of all-cause mortality in the previous CHD
      group was significantly increased for ST depression (by 64%), the ECG estimate of
      left ventricular mass (by 48%), and previous myocardial infarction (by 34%). In
      conclusion, we found no evidence that the relative risk of mortality for ECG
      abnormalities is lower in women than in men.

PMID- 16442388
TI  - Effectiveness of "direct" stenting without balloon predilatation (from the
      Multilink Tetra Randomised European Direct Stent Study [TRENDS]).
AB  - The purpose of the TRENDS trial was to assess the safety, efficacy, and cost
      effectiveness of a no-predilatation ("direct") stenting strategy in the treatment
      of de novo native coronary artery lesions using the Multilink Tetra stent system.
      In this multicenter, prospective clinical trial, 1,000 patients were randomized
      (1:1) to receive a Multilink Tetra stent with or without balloon predilatation.
      The primary outcome measurement was major adverse cardiac events (MACEs) at 30
      days; secondary end points included resource utilization (including procedural
      duration, equipment use, and length of hospital stay), MACEs, and angiographic
      binary restenosis at 180 days. In the predilatation group, 587 stents were
      implanted in 499 patients; in the direct group, 579 stents were implanted in 501
      patients. In the direct group, stents in 31 lesions (5.7%) required predilatation
      and multivariate analysis identified calcification (odds ratio 5.81), angulation
      (odds ratio 5.34), and preprocedural minimal lumen diameter (odds ratio 0.09) as
      direct stenting failure. MACEs at 30 days were similar in the 2 groups, with 19
      (3.8%) in the predilatation group and 13 (2.6%) in the direct group (p = NS).
      Resource utilization favored the direct strategy, with decreases in balloon use,
      contrast media, and procedure time, but a larger number of guiding catheters was
      used. The 180-day MACE rate of 9.8% in the direct group was not significantly
      less than the rate of 10.8% in the predilatation group (p = NS). Quantitative
      angiographic follow-up at 6 months demonstrated in-stent binary restenotic rates
      of 11.4% in the predilatation group (late loss 0.88 +/- 0.53 mm) and 12.3% in the
      direct group (late loss 0.82 +/- 0.51 mm, p = NS) and in-segment restenosis rates
      of 12.2% and 13.4%, respectively (p = NS). In conclusion, a direct stenting
      strategy with the Multilink Tetra stent was feasible and safe in 94% of lesions
      and associated with lower resource utilization compared with a predilatation
      approach. Direct stenting was not associated with significantly lower MACE and
      target lesion revascularization rates and had no effect on late angiographic
      follow-up, with similar late loss reflecting an identical biologic response to
      bare metal stent placement.

PMID- 16442389
TI  - Hospital resources consumed in treating complications associated with
      percutaneous coronary interventions.
AB  - Nearly 9.5% of all Medicare beneficiaries who undergo a percutaneous coronary
      intervention (PCI) procedure develop > or =1 of 7 acute complications. This study
      used 2 approaches (regression analysis and propensity-matched samples) to
      estimate the cost of selected complications, based on administrative data from
      335,477 Medicare beneficiaries who underwent PCI during a hospitalization in
      fiscal year 2002. Selected complications included hospital mortality,
      emergency/urgent coronary artery bypass surgery, postoperative stroke, acute
      renal failure, vascular complications, septicemia, and adult respiratory distress
      syndrome. The observed average cost of a PCI hospitalization for patients who did
      not develop complications was 13,861 dollars +/- 9,635 dollars, with an average
      length of stay of 3.0 +/- 3.2 days, compared with 26,807 dollars +/- 27,596
      dollars and 8.0 +/- 8.9 days for patients who did develop complications.
      Estimates of the adjusted incremental hospital cost of treating any acute
      complication except death varied from a high of 33,030 dollars for patients who
      developed septicemia to a low of 4,278 dollars for those who developed vascular
      complications, whereas estimates of the incremental length of stay ranged from a
      high of 12.3 days for patients who had septicemia to a low of 1.8 days for
      patients who had vascular complications. In conclusion, we found that the
      incremental hospital resources that are consumed to treat patients with acute PCI
      complications are large compared with the cost of an uncomplicated PCI
      hospitalization.

PMID- 16442390
TI  - Comparison of coronary calcium and stress myocardial perfusion imaging in
      apparently healthy siblings of individuals with premature coronary artery
      disease.
AB  - Detection of subclinical coronary atherosclerosis is possible using exercise
      myocardial perfusion imaging for inducible ischemia or multidetector computed
      tomography for coronary artery calcium (CAC), which is used to detect subclinical
      coronary atherosclerosis. The extent to which these screening tests converge in
      an asymptomatic population that is at increased risk for coronary artery disease
      remains unknown. We compared the concordance of findings in 260 asymptomatic
      middle-age siblings of hospitalized index patients <60 years of age with
      documented coronary artery disease. All subjects underwent maximal exercise
      testing with postexercise and delayed attenuation-corrected thallium single
      photon emission computed tomography and multidetector computed tomography for
      CAC. An abnormal exercise single-photon emission computed tomographic (SPECT)
      result occurred in >50% of subjects with a CAC score >100, but also in 12% with
      no CAC, 9% with CAC scores of 1 to 10, and 20% with CAC scores of 11 to 100. In
      subjects with an abnormal exercise SPECT result, 59% had CAC scores < or =100.
      Overall, there was only a modest agreement between an abnormal exercise SPECT
      result and high CAC scores. In conclusion, although moderate or severe CAC is
      often associated with inducible ischemia, the absence of CAC or the presence of
      only mild CAC by no means precludes inducible myocardial ischemia. These
      screening tests may reflect different aspects or stages of coronary disease in an
      asymptomatic middle-age population.

PMID- 16442391
TI  - Combined prognostic utility of ST segment in lead aVR and troponin T on admission
      in non-ST-segment elevation acute coronary syndromes.
AB  - Many studies have shown that ST-segment depression is a strong predictor of poor
      outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE
      ACSs); however, lead aVR was not considered in these studies. The present study
      examined the prognostic usefulness of the 12-lead electrocardiogram in
      combination with biochemical markers in 333 patients with NSTE-ACS. ST-segment
      deviation of > or =0.5 mm was considered clinically significant. Coronary
      angiography was performed a median of 3 days after admission in all patients. The
      primary end point was the composite of death, myocardial infarction, and urgent
      revascularization at 90 days. ST-segment elevation in lead aVR (odds ratio 13.8,
      95% confidence interval 1.43 to 100.9, p = 0.03) and increased troponin T (odds
      ratio 7.9, 95% confidence interval 1.22 to 123.8, p = 0.04) were the only
      independent predictors of restricted events (death or myocardial infarction) at
      90 days. ST-segment elevation in lead aVR (odds ratio 12.8, 95% confidence
      interval 4.80 to 33.9, p < 0.0001) and increased troponin T (odds ratio 2.03, 95%
      confidence interval 1.20 to 4.29, p = 0.04) were also the only independent
      predictors of adverse events (death, myocardial infarction, or urgent
      revascularization) at 90 days. When ST-segment status in lead aVR was combined
      with troponin T, patients with ST-segment elevation in lead aVR and increased
      troponin T had the highest rates of left main or 3-vessel coronary disease (62%)
      and 90-day adverse outcomes (47%). In conclusion, our findings suggest that ST
      segment status in lead aVR combined with troponin T on admission is a simple and
      useful clinical tool for early risk stratification in patients with NSTE-ACS.

PMID- 16442392
TI  - Heterogeneity of neointimal distribution of in-stent restenosis in patients with
      diabetes mellitus.
AB  - Diabetes mellitus is an independent predictor of restenosis after percutaneous
      coronary intervention. The pattern of restenosis after bare metal stent
      implantation in diabetic patients was examined with 3-dimensional intravascular
      ultrasound analysis. Lumen and stent were manually traced at every 0.5-mm
      interval in stented segments. Using Simpson's method, stent, luminal, and
      neointimal (stent minus lumen) volumes were calculated and average area was
      calculated as volume data divided by length. To measure the cross-sectional and
      longitudinal severities of luminal encroachment by the neointima, percent
      neointimal area (neointimal area divided by stent area) and neointimal
      hyperplasia 50 (IH50) (defined as percent stent length with percent neointimal
      area >50%) were calculated. In 278 patients (68 with diabetes and 210 without
      diabetes), there was a significantly higher percentage of maximal percent
      neointimal area with significantly longer percent stent length that was severely
      encroached by the neointima in diabetic patients. Diabetic patients showed a more
      heterogenous pattern of the neointima after bare metal stenting, resulting in
      longer high-grade obstruction segments. This may have important implications for
      stent design and pharmacokinetic properties of next-generation drug-eluting
      technology for this complex patient subset.

PMID- 16442393
TI  - Usefulness of multidetector row spiral computed tomography with 64- x 0.6-mm
      collimation and 330-ms rotation for the noninvasive detection of significant
      coronary artery stenoses.
AB  - Eighty-four patients with suspected coronary artery disease were studied to
      determine the accuracy of noninvasive coronary angiography using a multidetector
      computed tomographic scanner with 64- x 0.6-mm collimation and 330-ms gantry
      rotation. All coronary artery segments with a diameter >1.5 mm were assessed with
      respect to stenoses >50% decreased diameter. Results were compared with
      quantitative coronary angiographic findings. After exclusion of unevaluable
      coronary segments (4%), multidetector computed tomography demonstrated a
      sensitivity of 93%, a specificity of 97%, and a negative predictive value of 100%
      in a per-segment analysis. In a per-artery analysis, 15 of 336 arteries (4%) were
      unevaluable. Sensitivity and specificity in evaluable arteries were 95% and 93%,
      respectively. In a per-patient analysis (81 of 84 patients included), sensitivity
      and specificity were 96% and 91%, respectively.

PMID- 16442394
TI  - Clinical and angiographic analysis with a cobalt alloy coronary stent (driver) in
      stable and unstable angina pectoris.
AB  - The Clinical and Angiographic analysis with a Cobalt Alloy Coronary Stent
      (Driver) (CLASS) study was a prospective, nonrandomized, multicenter study
      designed to assess the safety and efficacy of a cobalt-chromium alloy-based stent
      in patients with stable or unstable angina pectoris. A total of 203 lesions were
      treated in 202 enrolled patients. The percentage of major adverse cardiac event
      free patients was 87.6% (177 of 202) at 6 months (primary safety end point; major
      adverse cardiac events were defined as death, myocardial infarction, emergency
      bypass surgery, or target lesion revascularization [percutaneous transluminal
      coronary angioplasty or coronary artery bypass grafting]). The angiographic
      success rate (primary efficacy end point) was 100%, and the procedural success
      rate was 98%. The binary in-stent restenosis rate at 6 months was 12.6%. Our
      results have demonstrated that the Driver cobalt-chromium alloy stent can be used
      with a low 6-month incidence of major adverse cardiac events, a low 6-month
      binary restenosis rate, and high angiographic and procedural success rates.

PMID- 16442395
TI  - Usefulness of T-wave loop and QRS complex loop to predict mortality after acute
      myocardial infarction.
AB  - The aim of the study was to assess whether parameters based on the T-wave loop
      and QRS loop predict mortality, and cardiac mortality in particular, during
      follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients
      with AMI (n = 437), treated according to contemporary guidelines, underwent
      digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5
      to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width
      and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop
      dispersion, and co-sine of the angle between the main vectors of the T-wave and
      QRS loops (TCRT), were calculated using a custom-made software package. During an
      average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53
      deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters
      that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62
      vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for
      TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for
      clinical risk markers in the Cox regression analysis, TWLD still significantly
      predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive
      power. TWLD did not have significant univariate or multivariate association with
      noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave
      loop is a specific predictor of cardiac death and independent of the clinical
      risk markers in the current treatment era of patients with AMI.

PMID- 16442396
TI  - Comparison between contrast echocardiography and magnetic resonance imaging to
      predict improvement of myocardial function after primary coronary intervention.
AB  - The relative merits of myocardial contrast echocardiography (MCE) and magnetic
      resonance imaging (MRI) to predict myocardial function improvement after
      percutaneous coronary intervention have not been evaluated until now. We studied
      35 consecutive patients with acute myocardial infarction who underwent
      percutaneous coronary intervention using MCE and MRI and first-pass imaging for
      evaluation of myocardial perfusion. Delayed-enhanced MRI was included as another
      method to differentiate viable from infarcted tissue. MCE was performed by power
      modulation and intravenous Sonovue. A 16-segment model of the left ventricle was
      used to analyze all myocardial contrast echocardiograms and magnetic resonance
      images. At 60 days of follow-up, MCE showed improvement of function in 115 of 192
      (60%) dysfunctional segments. The sensitivity, specificity, and accuracy for the
      prediction of functional improvement were comparable among MCE (87%, 90%, and
      88%), first-pass MRI (87%, 60%, and 79%), and delayed-enhancement MRI (75%, 100%,
      and 82%, respectively, all p = NS). In conclusion, MCE and MRI allowed for
      prediction of myocardial function improvement after percutaneous coronary
      intervention. MCE had a comparable accuracy and, as a bedside technique, may be
      an alternative tool in the acute phase of acute myocardial infarction.

PMID- 16442397
TI  - Assessment of estrogen status as a marker of prognosis in women with symptoms of
      suspected coronary artery disease presenting for stress testing.
AB  - Estrogen status (ES) has previously been shown to be a marker of angiographic
      outcome in women. In light of this finding, a reevaluation of ES as a marker of
      prognosis was undertaken. Two thousand one hundred forty-three women who
      underwent stress testing for symptoms of suspected coronary disease were studied.
      ES was defined according to menopausal, ovarian, and hormone replacement therapy
      status. The end points of interest were all-cause mortality, cardiac death, and
      nonfatal myocardial infarction. Survival analysis was performed using the Kaplan
      Meier method and Cox regression analysis with censoring at revascularization.
      Compared with 1,362 ES-positive women, the 781 ES-negative women had a higher
      frequency of unfavorable end points (all-cause death: ES positive 31 [2.3%] vs ES
      negative 94 [12%], p < 0.0001, cardiac death: ES positive 11 [0.8%] vs ES
      negative 38 [4.9%], p < 0.0001, and nonfatal myocardial infarction: ES positive
      11 [0.8%] vs ES negative 17 [2.2%], p = 0.007). The Kaplan-Meier curve analysis
      indicated that ES was a marker of cardiac risk (p < 0.0001) in all women, as well
      as in postmenopausal women. Multivariate Cox regression analysis revealed that ES
      was an independent marker of risk (p < 0.001) when considered with other standard
      risk factors. Using logistic regression and area under the curve analyses, ES had
      incremental value compared with standard risk factors. In conclusion, ES appears
      to be an easily discernible independent marker of risk that provides incremental
      prognostic information compared with standard clinical variables in women with
      symptoms of suspected coronary disease presenting for stress testing.

PMID- 16442398
TI  - Search for an optimal atherogenic lipid risk profile: from the Framingham Study.
AB  - Recent guidelines have targeted low-density lipoprotein (LDL) cholesterol for
      treatment of dyslipidemia. A lack of clear demarcation of potential coronary
      heart disease (CHD) cases solely on the basis of LDL cholesterol indicates the
      need to consider the dyslipidemic risk in the context of a lipid and risk factor
      profile. We prospectively examined the influence of individual lipids and their
      ratios on 20-year CHD development in 2,439 men and 2,812 women participating in
      the Framingham Offspring Study. The influence of the total/high-density (HDL)
      cholesterol ratio on CHD risk was examined in tertiles of LDL cholesterol and
      total cholesterol levels. During the 20-year period, 566 CHD events occurred in
      men and 327 events in women. The CHD risk increased stepwise two- to threefold in
      men and women from the first to third tertile of total/HDL cholesterol ratio,
      irrespective of the level of total or LDL cholesterol level. In men, the LDL
      cholesterol level reflected the lowest risk factor adjusted quintile 5 to
      quintile 1 relative risk (1.85), and the total/HDL cholesterol ratio predicted
      the greatest risk (relative risk 2.9). In women, LDL cholesterol imparted the
      highest risk of the individual lipids (relative risk 3.9), and this was not
      exceeded by the lipid ratio (relative risk 3.8). In conclusion, the levels of
      components of the total/HDL cholesterol ratio have little influence on its
      prediction of CHD. In men, elevated LDL need not be treated aggressively if the
      total/HDL cholesterol ratio is low. Conversely, modest elevations of LDL may
      warrant more aggressive treatment if the ratio is high. In women, the ratio is
      also a good CHD predictor, but a combination of a high ratio accompanied by high
      LDL cholesterol may warrant more aggressive therapy.

PMID- 16442399
TI  - Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in
      patients on statin drugs.
AB  - The objective of this study was to show that plant sterols in tablet form provide
      additional low-density lipoprotein (LDL) cholesterol lowering for patients on
      statin therapy. Dispersible phytosterol tablets were tested in a double-blind,
      placebo-controlled, parallel clinical trial. Twenty-six patients who were
      following the American Heart Association Heart Healthy Diet and on long-term
      statin therapy were studied for 9 weeks. After 3 weeks of placebo treatment, the
      subjects were randomized to receive either 1.8 g of soy stanols or placebo for 6
      weeks in addition to their usual statin regimen. Stanol tablets reduced LDL
      cholesterol 9.1% (p = 0.007) or 12.2 mg/dl. Total cholesterol was reduced by 12.9
      mg/dl (p = 0.03). A strong inverse correlation (r(s) = -0.82, p = 0.0007) was
      found between the baseline LDL cholesterol and the percent change in LDL
      cholesterol observed after stanol treatment. The additional LDL cholesterol
      lowering with stanol/lecithin tablets provided a potential adjunctive therapy for
      patients who have not reached their target LDL cholesterol goal during statin
      therapy.

PMID- 16442400
TI  - Effects of long-term vegetarian diets on cardiovascular autonomic functions in
      healthy postmenopausal women.
AB  - The incidence of cardiovascular disease is higher in postmenopausal women than in
      premenopausal women. We hypothesized that long-term vegetarian diets might
      modulate cardiovascular autonomic functions measured by frequency-domain
      techniques in healthy postmenopausal women. A total of 35 healthy vegetarians
      (mean age +/- SEM 55.0 +/- 1.3 years) who had been vegetarians for > or =2 years
      and 35 omnivores (55.1 +/- 1.4 years) participated in this study. These subjects
      were all postmenopausal without hormone replacement therapy. Fluctuations in
      arterial blood pressure and heart rate variability were diffracted into low
      frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.4 Hz) segments.
      Cardiovascular autonomic functions and baroreflex sensitivity were evaluated by
      specific frequency-domain measures. The vegetarians had statistically lower
      systolic and diastolic blood pressure, and lower serum total cholesterol, low
      density lipoprotein cholesterol, triglycerides, fasting blood sugar, and
      hemoglobin levels compared with the nonvegetarians. They also exhibited a
      significantly higher high-frequency power of heart rate variability and increased
      baroreflex sensitivity than did omnivores. No statistical differences were found
      in the low-frequency/high-frequency ratio or percentage of low frequency of heart
      rate variability between the 2 groups. In conclusion, in addition to the lower
      blood pressure and lipid concentrations in vegetarians, long-term vegetarian
      diets may facilitate vagal regulation of the heart and increase baroreflex
      sensitivity in healthy postmenopausal women, without increasing the sympathetic
      modulations of the cardiovascular system.

PMID- 16442401
TI  - Gender-related differences in patients with atrioventricular nodal reentry
      tachycardia.
AB  - The present study sought to assess the extent of gender differences in
      electrophysiologic parameters in patients with atrioventricular nodal reentrant
      tachycardia (AVNRT). The study population consisted of 203 patients (women/men
      ratio 2:1) who underwent slow pathway ablation. Patients with associated heart
      disease experienced the first episode of tachycardia at a significantly older age
      than patients with lone AVNRT (women 50 +/- 18 vs 29 +/- 15 years, p < 0.0001;
      men 45 +/- 20 vs 31 +/- 17 years, p = 0.01). Sinus cycle length (797 +/- 142 vs
      870 +/- 161 ms, p = 0.0001), HV interval (41 +/- 7 vs 45 +/- 8 ms, p = 0.0001),
      atrioventricular (AV) block cycle length (348 +/- 53 vs 371 +/- 75 ms, p = 0.01),
      slow pathway effective refractory period (ERP) (258 +/- 46 vs 287 +/- 62 ms, p =
      0.006), and tachycardia cycle length (354 +/- 58 vs 383 +/- 60 ms, p = 0.001)
      were shorter in women. No gender differences were noted in fast pathway ERP and
      ventriculoatrial (VA) block cycle length. In women, an AV block cycle length <350
      ms along with a VA block cycle length <400 ms predicted tachycardia induction
      without the need for autonomic intervention, with a positive predictive value of
      93% (sensitivity 71%, specificity 82%). No such cut-off values could be found in
      men. The acute success rate (100% vs 98%) and the recurrence rate (3% vs 6%) were
      similar for the 2 genders. In conclusion, in patients with lone AVNRT, the onset
      of symptoms occurred at a younger age than in patients with concomitant heart
      disease. Women had shorter slow pathway refractory periods, AV block cycle
      lengths, and tachycardia cycle lengths. No gender differences were noted in the
      fast pathway ERP. Therefore, women have a wider "tachycardia window" (i.e., the
      difference between the fast and slow pathway refractory periods), a finding that
      may explain their greater incidence of AVNRT.

PMID- 16442402
TI  - Prevalence and predictors of electrical storm in patients with implantable
      cardioverter-defibrillator.
AB  - Identifying predictors of electrical storm in patients with implantable
      cardioverter-defibrillators (ICDs) could help identify those at risk and reduce
      the incidence of this emergency situation, which has a detrimental effect on
      mortality and morbidity in patients with ICDs. This retrospective study sought to
      determine the prevalence and predictors of electrical storm in patients with
      ICDs. One hundred sixty-two patients (126 men; mean age 58 +/- 13 years) who
      received ICDs from January 2001 to January 2005 were included in the study.
      Clinical, electrocardiographic, and ICD stored data and electrograms were
      collected and analyzed. Twenty-two patients (14%) developed electrical storm
      during a mean follow-up of 14.3 +/- 10 months. Using Cox multiple regression
      analysis, it was found that an ejection fraction <25% (p = 0.007), QRS width > or
      =120 ms (p = 0.002), and a lack of adjunctive angiotensin-converting enzyme
      inhibitor and beta-blocker therapy (both p < 0.001) were correlated with a
      greater probability of electrical storm. Adjunctive amiodarone and digoxin
      therapy, indication of ICD implantation, and age were not correlated with the
      occurrence of electrical storm during follow-up (all p = NS). In conclusion,
      electrical storm is not uncommon in patients with ICDs. Optimum medical therapy
      with beta blockers and angiotensin-converting enzyme inhibitors could reduce the
      occurrence of electrical storm, and this especially should be considered in those
      at greater risk for this complication (i.e., those with left ventricular ejection
      fractions <25% and QRS widths > or =120 ms).

PMID- 16442403
TI  - Different criteria of cardiac resynchronization therapy and their prognostic
      value for worsening heart failure or major arrhythmic events in patients with
      idiopathic dilated cardiomyopathy.
AB  - There are still controversies about pertinent criteria for cardiac
      resynchronization therapy (CRT) and prophylactic indications for biventricular
      cardioverter-defibrillators, particularly in idiopathic dilated cardiomyopathy
      (IDC). This study compared several criteria for resynchronization therapy in IDC
      among those of several completed trials. In 201 patients with IDC, the relative
      risk for (1) death from heart failure (HF) or heart transplantation and (2)
      sudden death or sustained ventricular tachyarrhythmia were calculated separately
      according to the inclusion criteria of the Multisite Stimulation in
      Cardiomyopathy (MUSTIC), InSync, Multicenter InSync Randomized Clinical
      Evaluation (MIRACLE), Pacing Therapies for Congestive Heart Failure (PATH-CHF),
      Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure
      (COMPANION), and CONTAK studies. The percentage of patients meeting the criteria
      ranged from 6% for those of MUSTIC to 23% for those of CONTAK. In a follow-up of
      51 +/- 42 months, 28 patients died (15 from progressive HF, 13 from sudden
      death), 20 underwent heart transplantation, and 12 had sustained ventricular
      tachyarrhythmia. Relative risks of worsening HF ranged from 3.14 (95% confidence
      interval [CI] 1.41 to 6.99, p = 0.005) for the MIRACLE criteria to 4.63 (95% CI
      1.76 to 12.2, p = 0.0019) for the MUSTIC criteria. Only the CONTAK criteria were
      significantly associated with a risk for major arrhythmic events (2.65, 95% CI
      1.19 to 5.95, p = 0.018). Arrhythmic events constituted 16% of all cardiac events
      for the MUSTIC patients, 11% for InSync patients, 31% for PATH-CHF patients, 36%
      for MIRACLE patients, 38% for COMPANION patients, and 42% for CONTAK patients. In
      conclusion, in IDC, the less restrictive criteria for CRT were associated with
      the greatest risk for arrhythmic events. In contrast, patients with the MUSTIC
      criteria for CRT mainly had a risk for worsening HF and may not benefit from
      biventricular cardioverter-defibrillators.

PMID- 16442404
TI  - Comparative cost-effectiveness of B-type natriuretic peptide and echocardiography
      for predicting outcome in patients with congestive heart failure.
AB  - Two-dimensional echocardiographic and Doppler variables and B-type natriuretic
      peptide (BNP) can predict outcomes in patients with congestive heart failure
      (CHF). However, there is a paucity of data on the relative cost-effectiveness of
      these modalities in predicting outcome. One hundred sixteen patients hospitalized
      with CHF underwent simultaneous BNP and Doppler echocardiographic examinations
      once ready for discharge. The ability of these variables to determine the primary
      end point (cardiac death or rehospitalization for CHF) was determined. The cost
      effectiveness ratios (CER) of 2-dimensional variables, Doppler indexes, and BNP
      were calculated for prediction of the primary end point. Follow-up was completed
      in 110 of 116 patients at a mean of 527 days after hospital discharge. Fifty-four
      patients (50%) reached the primary end point (37 rehospitalizations for CHF and
      17 cardiac deaths). When added to a history of admission to the hospital in the
      preceding year for CHF, a comprehensive Doppler echocardiographic study predicted
      52 of 54 events, with a CER of 729.10 dollars, whereas BNP predicted 47 of 54
      events (CER 49.98 dollars; p < 0.001 for CER comparison). In patients admitted to
      hospitals with CHF, predischarge BNP is more cost-effective than comprehensive
      Doppler echocardiographic examination for the prediction of future cardiac death
      or rehospitalization for CHF.

PMID- 16442406
TI  - Comparison of the efficacy and safety profiles of intravenous vitamin K and fresh
      frozen plasma as treatment of warfarin-related over-anticoagulation in patients
      with mechanical heart valves.
AB  - Patients on warfarin for mechanical heart valves are at increased risk for
      thromboembolic events and intracranial hemmorhage. In current guidelines, a low
      dose of vitamin K is the recommended treatment for moderate over-anticoagulation
      based on studies in which only minority patients participating had mechanical
      heart valves. We performed a randomized controlled trial to compare the efficacy
      and safety profile of low-dose intravenous vitamin K and fresh frozen plasma
      (FFP) for patients with mechanical heart valves and mild to moderate over
      anticoagulation (international normalized ratio [INR] 4 to 7). In a 24-month
      period, we randomized 102 patients to (1) vitamin K or (2) FFP. The baseline INR
      at presentation between the vitamin K group and the FFP group was 4.61 +/- 0.007
      vs 4.78 +/- 0.07 (p = 0.11). Six hours after treatment, patients in the FFP group
      had a significantly lower mean INR compared with the vitamin K group (2.75 +/-
      0.06 vs 3.44 +/- 0.10, p = 0.01). No patient in both groups had over-correction
      (INR < 2). One week later, there was no significant difference in mean INR
      between both groups (2.7 +/- 0.11 vs 2.56 +/- 0.12, p = 0.41). Fifty-eight
      percent of patients in the FFP group and 51% in the vitamin K group had an INR
      within the target range. There were no adverse reactions or outcomes in both
      groups. In conclusion, intravenous low-dose vitamin K is a safe alternative to
      FFP infusion for warfarin overdose in patients with mechanical heart valves.

PMID- 16442405
TI  - Particulate air pollution and hospital admissions for congestive heart failure in
      seven United States cities.
AB  - The association between short-term elevations in ambient particulate air
      pollution and increased cardiovascular morbidity and mortality is well
      documented. Ambient particles may also trigger acute decompensation in patients
      with congestive heart failure (CHF), but this hypothesis has not been evaluated
      in a systematic manner. This study evaluated the association between daily levels
      of respirable particulate matter of aerodynamic diameters < or =10 microm (PM10)
      and the rate of hospitalization from the emergency room for CHF in Medicare
      recipients (age > or = 65 years) in 7 United States cities from 1986 and 1999.
      The time-stratified case-crossover design was used to separately estimate the
      effect of a 10 microg/m3 increase in PM10 in each city. A combined random-effects
      estimate was then obtained from the city-specific effect estimates. There were
      292,918 admissions with primary diagnoses of CHF during the observation period.
      Overall, a 10 microg/m3 increase in PM10 was associated with a 0.72% (95%
      confidence interval 0.35% to 1.10%) increase in the rate of admission for CHF on
      the same day. The effect of PM10 appeared to be less in patients with secondary
      diagnoses of hypertension. There was no consistent effect modification by age,
      gender, race, or any other secondary diagnosis evaluated. In conclusion, these
      results support the hypothesis that elevated levels of particulate air pollution,
      below the current limits set by the United States Environmental Protection
      Agency, are associated with an increase in the rate of hospital admission for
      exacerbation of CHF.

PMID- 16442407
TI  - Effect of acute unloading via head-up tilt on QTc prolongation in patients with
      ischemic or non-ischemic cardiomyopathy.
AB  - Patients with advanced cardiomyopathy develop prolongations in ventricular
      myocyte action potential duration that are reflected by prolongations of QT
      intervals on surface electrocardiograms. Recent studies demonstrate that the
      placement of a left ventricular (LV) assist device, which induces profound
      cardiac decompression, acutely increases QT intervals within hours. The goal of
      this study was to use head-up tilt (HUT) to examine electrocardiographic
      responses to cardiac unloading in patients with cardiomyopathy. Surface
      electrocardiograms were analyzed during HUT in 21 patients with cardiomyopathy
      (ejection fraction <30%) and in 33 age-matched controls. Four to 6 different QT
      and RR intervals were measured at baseline (supine), at 5 and 25 minutes after
      HUT. The heart-rate-adjusted QT interval (QTc) was calculated using Bazett's
      formula. The mean QTc in control patients decreased at 5 minutes (426 +/- 31 vs
      418 +/- 28 ms, p < 0.05, vs supine) and was unchanged at 25 minutes (426 +/- 31
      vs 423 +/- 25 ms, p = NS, vs supine). However, in patients with cardiomyopathy,
      there was a significant increase in QTc during HUT (455 +/- 45 vs 473 +/- 42 and
      479 +/- 42 ms, p < 0.001, vs supine). The change in heart rate during HUT did not
      differ between patients with cardiomyopathy and controls. In conclusion, HUT is
      associated with the immediate prolongation of myocardial repolarization in
      patients with cardiomyopathy. This response was not seen in age-matched controls.
      These results suggest that adaptations to chronic cardiac distention may include
      processes that help accelerate repolarization. Conversely, the prolongation of
      repolarization after unloading may modulate myocardial relaxation and
      arrhythmogenic risk.

PMID- 16442408
TI  - High risk of ventricular arrhythmias in patients with nonischemic dilated
      cardiomyopathy presenting with syncope.
AB  - It is not entirely clear whether the presentation of syncope in patients with
      nonischemic dilated cardiomyopathy (NIDC) is an ominous prognostic indicator,
      because randomized controlled implantable cardioverter-defibrillator (ICD) trials
      generally exclude such patients. This study compared 108 consecutive patients
      with NIDC presenting with syncope with 71 consecutive patients with NIDC who
      presented with sustained ventricular arrhythmias, with regard to freedom from any
      ventricular arrhythmias or life-threatening arrhythmias and all-cause mortality.
      There was no significant difference between the groups in the 3 outcomes during
      the follow-up of 43.5 +/- 32.1 months. Male gender and ICD therapy predicted
      increased risk for any ventricular arrhythmias. A reduced left ventricular
      ejection fraction and increased age were predictive of increased mortality. In
      conclusion, patients with NIDC presenting with syncope are a high-risk group,
      with event rates similar to patients with NIDC presenting with sustained
      arrhythmias, and should be considered for ICD therapy.

PMID- 16442409
TI  - Transthoracic echocardiographic predictors of left atrial appendage thrombus.
AB  - Transesophageal echocardiography (TEE) is commonly performed to detect the
      presence of a left atrial appendage (LAA) thrombus in the setting of an embolic
      event or before an anticipated electrical cardioversion for atrial fibrillation.
      The predictive value of transthoracic echocardiographic (TTE) findings in these
      patients has not been well defined. This study evaluated whether TTE findings can
      predict LAA thrombi using TEE as the gold standard for the identification of LAA
      thrombi. From November 1995 to March 2003, 10,753 patients underwent TEE to
      exclude LAA thrombi after embolic events or before cardioversion. Of these, 3,768
      patients had complete TTE examinations performed <2 weeks before undergoing TEE.
      Demographics, TTE, and cardiac rhythm variables were analyzed using univariate
      and multivariate logistic regression to identify predictors of LAA thrombi
      diagnosed on subsequent TEE. LAA thrombi were identified by TEE in 199 patients
      (5.3%). Several TTE variables predicted LAA thrombi by TEE, including mitral
      stenosis, atrial fibrillation, tricuspid regurgitation, valvular prosthesis, left
      ventricular dysfunction, and right ventricular dysfunction. Mitral regurgitation
      was associated with a reduced risk for LAA thrombi (odds ratio 0.61, p = 0.003).
      A structurally normal heart in sinus rhythm (n = 247, 6.9%) had a 100% negative
      predictive value for LAA thrombi. In conclusion, several TTE variables were found
      to be predictive of LAA thrombi. The likelihood of LAA thrombi being found on TEE
      was infinitely small in the absence of these variables and the presence of sinus
      rhythm.

PMID- 16442410
TI  - Frequency and management of thrombocytopenia with the glycoprotein IIb/IIIa
      receptor antagonists.
AB  - Glycoprotein IIb/IIIa receptor antagonists (GPRAs) are widely used in the
      management of a variety of patients with acute coronary syndromes. Major adverse
      reactions to these agents include bleeding and thrombocytopenia. Immune
      mechanisms responsible for severe thrombocytopenia seen with GPRAs have been
      hypothesized for all 3 agents currently available in the United States, although
      specific laboratory tests are not available for use in routine practice. A review
      of published research for GPRA-induced thrombocytopenia (GIT) is provided.
      Although the incidence of severe GIT is relatively low, the implications for
      patients are potentially life threatening. Prompt recognition of severe
      thrombocytopenia is essential to facilitate the necessary care of patients.
      Treatment strategies include the modification of drug regimens and other
      interventions targeting the reduction of immediate bleeding risk and the
      provision of supportive care measures. A review of published research supporting
      the conservative use of corticosteroids and intravenous gamma globulin in this
      syndrome is provided. Clinicians identifying severe thrombocytopenia after GPRA
      exposure are encouraged to report these events, following national and
      institutional guidelines.

PMID- 16442412
TI  - A call for more data.

PMID- 16442413
TI  - Relation of right ventricular free wall mechanical delay to right ventricular
      dysfunction as determined by tissue Doppler imaging.

PMID- 16442414
TI  - Hamilton Naki and Christiaan Barnard versus Vivien Thomas and Alfred Blalock:
      similarities and dissimilarities.

PMID- 16442415
TI  - Evidence-based surgery--inevitable?

PMID- 16442416
TI  - Evidence-based surgery.

PMID- 16442417
TI  - Evidence-based surgery.
AB  - Understanding the issues associated with surgical epidemiology,knowledge
      management, and evidence-based surgical practice has implications for clinicians
      in the community, surgeons in large metropolitan hospitals, surgeon scholars, and
      the academic surgeon. All need to have some understanding of not only the
      evaluation of the evidence and how to find it but, in addition, application of
      those concepts to continuous quality improvement and to closing a circle of
      surgical audit. If the surgical profession has an obligation to redefine clinical
      modus operandi and educational processes, the argument for formal training in
      aspects of clinical epidemiology during the surgical residency program is
      obvious,because all surgeons will benefit from those educational exercises.

PMID- 16442418
TI  - Knowledge management: a core skill for surgeons who manage.
AB  - The yawning gap between what we know and what we do has major implications for
      patients. By putting into practice what we know now, we will have a bigger impact
      on the health of individuals and populations than any drug or technology
      discovered in the new decade. The assumption underlying this article is that the
      gap can be closed by thinking, planning, analyzing, mobilizing,managing,
      personalizing, and using knowledge. There is, however,a risk that the attempted
      solution may perpetuate or aggravate the problem, and surgeons must be aware of
      the dangers of substituting thought for action, when knowledge management becomes
      an industry of its own, remote from the core activities of the organization and
      those who deliver them.

PMID- 16442419
TI  - Finding and appraising evidence.
AB  - Surgeons have tended to regard evidence-based medicine with a degree of
      skepticism. A variety of reasons for this have been proposed,ranging from the
      surgical personality to the nature of the research questions that occur when
      studying surgical treatment. The relative paucity of randomized trials of
      surgical treatment has been noted by many investigators, and there has been
      considerable debate about whether this reflects poorly on the scientific
      education of the surgical community or points to special problems in applying
      this methodology in this discipline. This debate has matured over the last 10
      years, and there is now greater understanding of the factors that make surgical
      operations difficult subjects for randomized trials; on the other hand, such
      trials are being done now more than ever before.

PMID- 16442420
TI  - Teaching evidence-based decision-making.
AB  - Evidence-based decision-making is important in surgery, but the nature of the
      work makes it difficult. Teaching it requires an interactive approach with a
      clinical team willing to consider it seriously,and to derive practical solutions.
      Decision-making and its influences must be understood, so that surgeons have a
      realistic idea of the role of evidence. Cognitive factors are particularly
      important.Strategies developed in the context of this knowledge are more likely
      to be adopted and used. Experts must be involved in searching for evidence and
      members of the management team in the learning process, the former to provide
      expertise on searching,the latter to ensure that the reasons for proposed changes
      are understood and treated sympathetically by those with financial control.

PMID- 16442421
TI  - Librarians, surgeons, and knowledge.
AB  - are indicative of the ferment of change brought about by the digital revolution,
      and of the continuing determination of health information professionals to rise
      to the challenges involved in supporting surgeons and everyone in the surgical
      team, as they endeavor to provide the best possible care for their patients.
      Libraries as we know them have changed, and are changing. The scholarly
      communications process is also undergoing profound transformation. The authors
      discuss these changes and their implications for surgeons.

PMID- 16442422
TI  - Evidence-based surgery: creating the culture.
AB  - Hospitals and professional bodies require a culture that supports surgeons in
      their quest for knowledge, and provides the technological and educational
      environment in which they can promote evidence-based surgery. Surgeons must
      influence the development of their local information technology systems for data
      collection and outcome analysis, and deliver training programs that instill an
      attitude of continually seeking evidence. Identification of clinical problems and
      critical appraisal of the literature need to be taught. Management structures and
      relationships that facilitate a joint approach to delivering high-quality
      systematic clinical care should be developed. The culture that supports these
      aims is also one in which patients can rely on safely receiving up-to-date and
      effective treatments from well-trained and trusted surgeons.

PMID- 16442423
TI  - Systematic reviews of surgical interventions.
AB  - All physicians are familiar with the type of general review articles found in
      many medical journals. Systematic reviews are different. They apply a strict,
      scientific methodology to the reviewing process to produce a review that is
      comprehensive, reliable, and as free from bias as possible. As a result,
      systematic reviews occupy the highest position in the "levels of evidence" tables
      associated with the practice of evidence-based health care. Systematic reviews
      relevant to surgery are no less relevant than systematic reviews in other areas
      of health care. They should be a prerequisite of any new research, a key
      component in decision making, and an opportunity for all surgical practitioners
      to get involved in the conduct and interpretation of research.

PMID- 16442424
TI  - Evaluating new surgical techniques in Australia: the Australian Safety and
      Efficacy Register of New Interventional Procedures-Surgical experience.
AB  - The Australian Safety and Efficacy Register of New Interventiona lProcedures
      Surgical (ASERNIP-S) exists primarily to assess new surgical technologies and
      techniques. It originally conducted systematic literature reviews, but now uses
      accelerated reviews, horizon scanning for emerging procedures, research and
      clinical audits,preparation of patient information, assistance with guideline
      development,and the production of research protocols of new surgical techniques.
      Future international cooperation and networking among health technology
      assessment groups will avoid duplication of effort and maximize outputs.
      Experience has shown that when surgeons lead in assessing new and emerging
      surgical techniques and technologies, the benefits of an evidence-based approach
      are realized, and the surgical community accepts the complementary role of
      evidence-based medicine in the provision of high-quality patient care.

PMID- 16442425
TI  - Evaluating surgical outcomes.
AB  - The study of outcomes has become essential for guiding quality of-care assessment
      and for clinical research. In this article, the properties and process of patient
      outcomes measurement are described. The limitations of traditional outcomes are
      discussed and contrasted with the emerging concept of "patient-centered"outcomes,
      measured by validated instruments to assess the effects of surgical interventions
      on health-related quality of life, functional status, pain, and patient
      satisfaction. The strengths and weaknesses of several measurement tools used in
      the surgical literature are evaluated. Finally, the authors introduce "composite
      outcomes" as a reflection of the multidimensional nature of modern patient care.

PMID- 16442426
TI  - Ethical issues in evidence-based surgery.
AB  - Evidence-based medicine, although ostensibly concerned with the research evidence
      underlying claims of efficacy for surgical procedures,has a direct connection
      with the ethics of surgical decision making. Questions of whether new procedures
      should ever be performed on patients outside of a formal research protocol, what
      the patient should be told about the uncertainties inherent in the use of
      nonvalidated innovative procedures, when formal evaluation is necessary, what
      form that evaluation should take, and how the burdens and results of such
      research can be distributed fairly all involve balancing competing ethical
      principles. Good ethics requires good facts, and evidence from well-controlled
      experiments provides best information upon which to base decisions in these areas
      and to build ethical surgical practice.

PMID- 16442427
TI  - Relative contributions of surgeons and decision support systems.
AB  - Evidence-based medicine came into focus in 1992 when scholars recognized the need
      for valid information required for optimal patient care. Because of the
      increasing volume and uncertain quality of new knowledge, traditional sources of
      information such as books and journals failed to meet the needs of busy
      practitioners.Evidence-based medicine promoted strategies for identifying and
      appraising relevant information and making it readily available. Surgeons face
      unique challenges in the recognition and application of best evidence. Evidence
      based surgery requires careful appraisal of the existing evidence, expanding the
      pool of level 1 evidence,and improving the availability of best evidence.
      Ultimately, the organization of systems will incorporate best evidence into the
      processes of care and will document the outcomes of care.

PMID- 16442428
TI  - Developing skills for evidence-based surgery: ensuring that patients make
      informed decisions.
AB  - Ensuring that the surgical decisions made by and with patients are fully informed
      is a challenge. Doctors and patients must work together, and to be successful
      they need support in the form of knowledge management and decision aids. This
      article emphasizes the importance of eliciting and honoring patients' personal
      valuations of alternative future health states, their attitudes to the specific
      risks and risk differences that are central to surgical decisions,and their
      attitudes to time trade-offs. The skills and habits necessary to accomplish this
      critical objective begin with nothing less than a genuine concern for patients
      and an ability to relate to the unique meaning that the present illness and its
      treatment have in their lives.

PMID- 16442429
TI  - Managing the evidence flood.
AB  - The problem of lack of transfer of knowledge in surgery is well illustrated by
      the variations in surgical practice across areas and countries. Surgery is not
      unique in this respect, and such variations have been documented in virtually all
      specialties and in primary care. The first issue is recognition that there is an
      inescapable and growing information problem. Unless we focus some of our research
      and practice effort on better organizing, filtering, and using the research that
      we have, the gap between what we know and what we do will continue to grow.

PMID- 16442430
TI  - Surgical decision-making: integrating evidence, inference, and experience.
AB  - Evidence-based medicine provides a well-developed framework for evaluation of
      clinical research. Well-designed and adequately powered randomized controlled
      trials provide the best information on therapeutic efficacy; however,
      extrapolation of the trials' conclusions to individual patients may be difficult,
      and for many important surgical problems, trial data are unavailable. A
      complementary approach of inferential decision-making helps address these
      limitations, and increases the clinician's confidence in the safety of an
      approach of unknown efficacy. Experience establishes norms and expectations, and
      emphasizes events that are uncommon but clinically important. Although it cannot
      eliminate uncertainty or controversy, the integration of analytic techniques of
      evidence, inference, and experience provides the surgeon with the best means of
      adapting treatment to the unique circumstances of the individual patient.

PMID- 16442431
TI  - Evidence-based surgical practice and patient-centered care: inevitable.
AB  - Evidence-based medicine provides a well-developed framework for evaluation of
      clinical research. Well-designed and adequately powered randomized controlled
      trials provide the best information on therapeutic efficacy; however,
      extrapolation of the trials' conclusions to individual patients may be difficult,
      and for many important surgical problems, trial data are unavailable. A
      complementary approach of inferential decision-making helps address these
      limitations, and increases the clinician's confidence in the safety of an
      approach of unknown efficacy. Experience establishes norms and expectations, and
      emphasizes events that are uncommon but clinically important. Although it cannot
      eliminate uncertainty or controversy, the integration of analytic techniques of
      evidence, inference, and experience provides the surgeon with the best means of
      adapting treatment to the unique circumstances of the individual patient.

PMID- 16442432
TI  - The influence of extensive vegetated roofs on runoff water quality.
AB  - The influence of extensive sedum-moss vegetated roofs on runoff water quality was
      studied for four full scale installations located in southern Sweden. The aim of
      the study was to ascertain whether the vegetated roof behaves as a sink or a
      source of pollutants and whether the age of a vegetated roof influences runoff
      quality. The runoff quality from vegetated roofs was also compared with the
      runoff quality from non-vegetated roofs located in study areas. The following
      metals and nutrients were investigated: Cd, Cr, Cu, Fe, K, Mn, Pb, Zn, NO3-N, NH4
      N, Tot-N, PO4-P, and Tot-P. The results show that, with the exception of
      nitrogen, vegetated roofs behave as source of contaminants. While in lower
      concentrations than normally found in urban runoff, some metals appear in
      concentrations that would correspond to moderately polluted natural water.
      Nitrate nitrogen is retained by the vegetation or soil or both. Apart from the
      oldest, the studied vegetated roofs contribute phosphate phosphorus to the
      runoff. The maintenance of the vegetation systems on the roofs has to be
      carefully designed in order to avoid storm-water contamination; for instance, the
      use of easily dissolvable fertilizers should be avoided.

PMID- 16442433
TI  - Evaluation of emission toxicity of urban bus engines: compressed natural gas and
      comparison with liquid fuels.
AB  - Emissions from a spark-ignition (SI) heavy-duty (HD) urban bus engine with a
      three-way catalyst (TWC), fuelled with compressed natural gas (CNG), were
      chemically analyzed and tested for genotoxicity. The results were compared with
      those obtained in a previous study on an equivalent diesel engine, fuelled with
      diesel oil (D) and a blend of the same with 20% vegetable oil (B20). Experimental
      procedures were identical, so that emission levels of the CNG engine were exactly
      comparable to the ones of the diesel engine. The experimental design was focused
      on carcinogenic compounds and genotoxic activity of exhausts. The results
      obtained show that the SI CNG engine emissions, with respect to the diesel engine
      fuelled with D, were nearly 50 times lower for carcinogenic polycyclic aromatic
      hydrocarbons (PAHs), 20 times lower for formaldehyde, and more than 30 times
      lower for particulate matter (PM). A 20-30 fold reduction of genotoxic activity
      was estimated from tests performed. A very high reduction of nitrogen oxides
      (NO(X)) was also measured. The impact of diesel powered transport on urban air
      quality, and the potential benefits deriving from the use of CNG for public
      transport, are discussed.

PMID- 16442434
TI  - Influence of set-up conditions of exposure indicators on the estimate of short
      term associations between urban pollution and mortality.
AB  - In the past few years many studies on air pollution and health based on time
      series have been carried out. Yet, this approach does not assess exposure to air
      pollution at an individual level but it is based on ambient concentrations
      measured by air quality monitoring networks. Questions on the estimates of
      exposure to pollutants have been raised, in particular the fact that background
      measuring stations only have been considered in the set up of pollution
      indicators. To assess the impact of exposure indicator characteristics on the
      results of time series analysis, two series (black smoke and sulfur dioxide,
      respectively) of exposure indicators to urban air pollution were set up taking
      into account a growing part of proximity measures (industrial sources) available
      in the studied urban area (Le Havre, France). For each pollutant, indicators
      distributions were almost similar, especially for black smoke. Whatever the
      pollutant, the most obvious heterogeneity could be observed between the 100%
      background indicator and the indicator including the arithmetic mean for all the
      stations (50% background stations and 50% proximity stations). Then the
      sensitivity of the associations between mortality and air pollution to these
      indicators was studied. These indicators did not show statistically significant
      differences in the estimated excess risk. Yet, confidence intervals were more
      statistically significant as the contribution of proximity stations was more
      substantial, in particular for SO2. To conclude, the use of proximity
      measurements did not influence dramatically on the mean estimates of the
      association between air pollution and mortality indicators in Le Havre. Therefore
      it does not seem relevant to include the data provided by the proximity stations
      in the urban exposure indicators within the context of the epidemiology
      monitoring system.

PMID- 16442435
TI  - A survey of endocrine disrupting chemicals (EDCs) in municipal sewage and animal
      waste effluents in the Waikato region of New Zealand.
AB  - We report the results of a recent survey of the concentration of natural
      estrogens (17beta-estradiol, 17alpha-estradiol, estrone, estriol) and the
      synthetic estrogen, 17alpha-ethynylestradiol in representative animal wastes and
      sewage treatment plant (STP) effluents in the Waikato region of New Zealand.
      Dairy farm effluent samples showed high levels of estradiol (19-1360 ng/L) and
      its breakdown product estrone (41-3123 ng/L) compared with piggery or goat farm
      effluents. The combined load for these estrogens (excluding beta epimer) varied
      from 60 to >4000 ng/L. The piggery effluent provided the lowest total estrogen
      load (46 ng/L), with estrone accounting for nearly 60% of the measured estrogens
      in this sample. The synthetic analogue, 17alpha-ethynylestradiol was detected
      only in one wastewater treatment plant sample, albeit at trace level. An estrogen
      receptor competitive binding assay was used to test the biological activity of
      the samples and confirmed that most agricultural waste samples contain high
      levels of estrogenic compounds. The potential of these wastes to cause endocrine
      disruption in the receiving ecosystem is unknown at present.

PMID- 16442436
TI  - Biomonitoring of the genotoxic potential of aqueous extracts of soils and bottom
      ash resulting from municipal solid waste incineration, using the comet and
      micronucleus tests on amphibian (Xenopus laevis) larvae and bacterial assays
      (Mutatox and Ames tests).
AB  - The management of contaminated soils and wastes is a matter of considerable human
      concern. The present study evaluates the genotoxic potential of aqueous extracts
      of two soils (leachates) and of bottom ash resulting from municipal solid waste
      incineration (MSWIBA percolate), using amphibian larvae (Xenopus laevis). Soil A
      was contaminated by residues of solvents and metals and Soil B by polycyclic
      aromatic hydrocarbons and metals. MSWIBA was predominantly contaminated by
      metals. Two genotoxic endpoints were analysed in circulating erythrocytes taken
      from larvae: clastogenic and/or aneugenic effects (micronucleus induction) after
      12 days of exposure and DNA-strand-breaking potency (comet assay) after 1 and 12
      days of exposure. In addition, in vitro bacterial assays (Mutatox and Ames tests)
      were carried out and the results were compared with those of the amphibian test.
      Physicochemical analyses were also taken into account. Results obtained with the
      amphibians established the genotoxicity of the aqueous extracts and the comet
      assay revealed that they were genotoxic from the first day of exposure. The
      latter test could thus be considered as a genotoxicity-screening tool. Although
      genotoxicity persisted after 12 days' exposure, DNA damage decreased overall
      between days 1 and 12 in the MSWIBA percolate, in contrast to the soil leachates.
      Bacterial tests detected genotoxicity only for the leachate of soil A (Mutatox).
      The results confirm the ecotoxicological relevance of the amphibian model and
      underscore the importance of bioassays, as a complement to physico-chemical data,
      for risk evaluation.

PMID- 16442438
TI  - Malaria parasite burden and treatment seeking behavior in ethnic communities of
      Assam, Northeastern India.
AB  - OBJECTIVES: The objectives of the study were to define the infectious reservoir
      of malaria with particular reference to transmission dynamics of Plasmodium
      falciparum, and to ascertain the disease trends in view of the existing
      containment practices and treatment seeking behavior in malaria endemic
      communities of Assam, India. METHODS: Cross-sectional surveys were conducted in
      population groups of malaria endemic districts of the state to determine parasite
      prevalence, and data were analysed retrospectively for the years 1991-2003 to
      ascertain the disease trends. Structured questionnaire based surveys were
      conducted to study the treatment seeking behavior and practices of healthcare
      providers. RESULTS: P. falciparum and P. vivax were the only two parasite species
      encountered, the former being in the majority (>60%). Malaria transmission was
      persistent, and a seasonal peak of P. falciparum was consistently observed during
      the months of heavy rainfall (April to September). Among children (5-15 years)
      there was a significantly higher malaria parasite rate as compared to the <5
      years age group and adults (>15 years). There was a decline in parasite rates for
      all age groups over the years of the study that could not be attributed to vector
      control intervention intensities and/or meteorological factors. CONCLUSIONS: The
      persistence of P. falciparum is attributed to the emergence of drug resistant
      varieties, inadequate interventions and treatment seeking patterns, and for its
      containment focused intervention measures are advocated in partnership with the
      communities.

PMID- 16442442
TI  - Current economic trends affecting the veterinary medical profession.
AB  - This article explores the economic trends affecting the future of the veterinary
      medical profession. Key aspects of demand and supply are considered, as are
      several broad-based institutional factors. Demand for veterinarians and
      veterinary medical services is demonstrating a definitive upward trend across the
      profession, led by a remarkable in-crease in consumers' willingness to spend on
      animal health care.Supply is also expanding through increased enrollments at
      colleges and schools of veterinary medicine and increased productivity and
      efficiency in private practice. Veterinarians' incomes are increasing, and some
      sectors of the profession offer outstanding financial opportunities. Provided
      that critical needs are met for 1) increased diversity and 2) continued
      improvement in the nontechnical capabilites of veterinarians, the outlook for the
      economic future of the veterinary medical profession is strong.

PMID- 16442439
TI  - Profile of infective endocarditis in a referral hospital over the last 24 years.
AB  - OBJECTIVES: To describe changes in demographic, clinical and micro-biological
      characteristics of infective endocarditis (IE), and to assess factors associated
      with an increased risk of death. METHODS: Episodes fulfilling the Duke criteria
      for definite IE were included. Data collected in 1980-1991, and 1992-2003 from
      IVDU and non-IVDU patients' records were collected, and changes within each group
      and between the groups analysed. RESULTS: There were 169 episodes of IE in IVDUs,
      and 114 in non-IVDUs. HIV-infected patients were 86 (82 IVDUs). Site of
      involvement, need for surgery, and case fatality rate (15.6% among IVDUs and
      11.3% non-IVDUs) did not change in both groups over time. Staphylococci and
      streptococci were the most commonly isolated organisms among IVDUs and non-IVDU,
      respectively; independent predictors of mortality among IVDUs were negative blood
      cultures [adjusted OR (AOR) 7.85], and fungal etiology (AOR 21.33). Among non
      IVDUs prosthetic heart valves had an AOR of 2.22 (95% CI 0.48-10.21); the
      proportion of negative blood cultures significantly increased. An higher case
      fatality rate was observed among HIV-positive patients (AOR 2.64 95% CI 0.85
      8.20). CONCLUSIONS: Late diagnosis and lack of etiological definition continue to
      represent the most important obstacles to an effective management of IE,
      suggesting the need for a wider use of molecular techniques in patients with
      suspected IE.

PMID- 16442440
TI  - Activation of ERK1/2 and TNF-alpha production are mediated by calcium/calmodulin,
      and PKA signaling pathways during Mycobacterium bovis infection.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG)-induced tumor necrosis factor
      (TNF)-alpha secretion via an extracellular signal-regulated kinase (ERK) mitogen
      activated protein kinase-dependent mechanism is an important host defence
      mechanism against Mycobacterium tuberculosis in human monocytes. We now define
      distinct signaling pathways that regulate induction of TNF-alpha and activation
      of ERK1/2 by intracellular signaling mechanisms during M. bovis infection. We
      determined that M. bovis BCG-induced ERK 1/2 activation occurs through a
      mechanism that requires intracellular calcium and likely involves a calmodulin
      sensitive step. In contrast, M. bovis BCG can induce p38 mapk activation by a
      calcium (Ca2+)/calmodulin-independent mechanism. Interestingly, we present
      evidence that M. bovis BCG activates protein kinase A (PKA), since pretreatment
      of monocytes with H-89, a inhibitor of PKA activity, blocked the ability of M.
      bovis BCG to induce ERK1/2 activation. These results were further supported by
      the fact that treatment of cells with KT5720, another well-described inhibitor of
      PKA activity, significantly diminished the effect of M. bovis BCG on ERK1/2
      activation. Furthermore, secretion of TNF-alpha in M. bovis-infected human
      monocytes was also dependent on Ca2+/calmodulin, and PKA pathways. Finally,
      addition of H-89 significantly diminished TNF-alpha mRNA expression in M. bovis
      infected human monocytes. These results indicate that the Ca2+/calmodulin, and
      PKA pathways play important regulatory roles in monocyte signaling upon M. bovis
      infection.

PMID- 16442443
TI  - Marketing veterinary services.
AB  - Marketing is a holistic process that goes far beyond a Yellow Page advertisement
      or a glossy brochure. A thorough evaluation of a market before entry, including
      best and worst case scenarios, is critical to mak-ing good investments.
      Veterinarians are fortunate to have a market that is largely protected by
      barriers to entry and characterized by reasonably high rates of return given
      minimal risk. Our market base continues to expand and, overall, remains fairly
      price insensitive. The extent to which a practice can align its capabilities with
      a product mix that ideally meets its clients' needs will ultimately determine its
      success.

PMID- 16442444
TI  - Contemporary issues of veterinary practice valuation and sale transactions.
AB  - This article comprises discussions on practices with little or no salable value,
      the determination and measurement of the value of a veterinary practice, the
      evolution of the small animal practice marketplace, the costs of selling a
      portion of a practice, lack of marketability discount, and C corporation issues.

PMID- 16442445
TI  - The gender shift in veterinary medicine: cause and effect.
AB  - The gender shift in veterinary medicine has paralleled other changes in debt and
      income. Cause and effect are complex and often confused. Popular notions of the
      priorities of the new generation of men and women are often not supported by
      research studies. Recent data reveal new insights into questions surrounding the
      gender issue.

PMID- 16442446
TI  - Current trends in animal law and their implications for the veterinary
      profession.
AB  - In the last decade, the veterinary profession has experienced many changes,
      including the birth of a new area of law known as "animal law," and an increased
      scrutiny by the legal community and veterinary state boards. This article
      provides a sampling of some of the more challenging issues the profession is
      facing in the early part of the 21st century, namely, guardianship versus
      ownership, the awarding of non-economic damages in negligence lawsuits, and
      challenges in maintaining medical records.

PMID- 16442447
TI  - Succession planning.
AB  - This article provides the reader with an appreciation of the diverse elements
      that go into a buy-sell, affiliation, or merger situation for veterinary
      practices. In the changing market place of American veterinary medicine, old
      paradigms no longer hold comfort. The generational differences are briefly
      explored herein as well as the new economic realities. A few examples are offered
      to illustrate just how much variability exists in the current business of
      veterinary medicine and the subsequent practice transitions needed to enhance
      value. Functioning models are explored, as well as affiliation and merger
      options. Practice valuation is discussed in general terms, referencing the
      cutting-edge factors. The six-point summary provides almost all practices a solid
      operational base for daily operations and succession planning.

PMID- 16442448
TI  - Buying and leasing real estate for veterinary hospitals.
AB  - The major factors to be considered in the real estate purchase decision are the
      interest rate, the depreciation schedule, the property appreciation, the income
      tax impact, and the impact of paying a principal payment as part of the real
      estate mortgage. All these factors must be compared with the costs of leasing.

PMID- 16442449
TI  - Four core communication skills of highly effective practitioners.
AB  - For 40 years, medical researchers have been studying physician-patient
      interactions, and the results of these studies have yielded three basic
      conclusions: physician-patient interactions have an impact on patient health,
      patient and physician satisfaction, adherence to medical recommendations, and
      malpractice risk; communication is a core clinical skill and an essential
      component of clinical competence; and appropriate training programs can
      significantly change medical practitioners' communication knowledge, skills, and
      attitudes. Many of these findings are applicable to the practice of veterinary
      medicine.

PMID- 16442450
TI  - Move your practice to new heights with down-to-earth hiring techniques.
AB  - Like preparing for intricate surgery, successful staffing requires preparation,
      mastery of the subject matter, and skill. The employees who work in veterinary
      practices form the basis of the business and reflect the owners' own values.
      Giving attention to what you want your practice to be, whom you want working with
      you, and how the environment keeps the staff productive matters. Identifying the
      right culture, hiring people who find congruence with the practice's culture, and
      consistently applying these principles will help your practice soar to new
      heights.

PMID- 16442451
TI  - Small animal practice: billing, third-party payment options, and pet health
      insurance.
AB  - Rising veterinary costs can keep some people from accepting necessary medical
      care for their pets. This article discusses viable alternative financing options.
      Each alternative comes with its own pros and cons. Practice owners will want to
      study the offerings carefully to find the best match for their practice and
      clients.

PMID- 16442452
TI  - Compliance: crafting quality care.
AB  - The concept of compliance involves the consistency and accuracy with which a
      client follows the regimen recommended by the veterinarian or other veterinary
      health care team member. Contrary to common belief, most compliance failures are
      not the direct result of a client's unwillingness to comply. This article will
      help the reader better appreciate the critical importance of effective
      communication by the entire veterinary health care team in achieving compliance.
      Success is predicated on an alliance between the practice team and the client.
      Certain paradigms surrounding compliance in veterinary practice are discussed,
      and the positive outcomes of compliance, including optimal patient care,
      exceptional client service, employee career growth, and economic ramifications,
      are explored.

PMID- 16442453
TI  - Patients' preference for involvement in medical decision making: a narrative
      review.
AB  - OBJECTIVE: This review aimed to clarify present knowledge about the factors which
      influence patients' preference for involvement in medical decision making.
      METHODS: A thorough search of the literature was carried out to identify
      quantitative and qualitative studies investigating the factors which influence
      patients' preference for involvement in decision making. All studies were
      rigorously critically appraised. RESULTS: Patients' preferences are influenced
      by: demographic variables (with younger, better educated patients and women being
      quite consistently found to prefer a more active role in decision making), their
      experience of illness and medical care, their diagnosis and health status, the
      type of decision they need to make, the amount of knowledge they have acquired
      about their condition, their attitude towards involvement, and the interactions
      and relationships they experience with health professionals. Their preferences
      are likely to develop over time as they gain experience and may change at
      different stages of their illness. CONCLUSION: While patients' preferences for
      involvement in decision making are variable and the process of developing them
      likely to be highly complex, this review has identified a number of influences on
      patients' preference for involvement in medical decision making, some of which
      are consistent across studies. PRACTICE IMPLICATIONS: By identifying the factors
      which might influence patients' preference for involvement, health professionals
      may be more sensitive to individual patients' preferences and provide better
      patient-centred care.

PMID- 16442454
TI  - Improvement of balance between work stress and recovery after a body awareness
      program for chronic aspecific psychosomatic symptoms.
AB  - OBJECTIVE: A 3-day residential body awareness program (BAP) was developed to
      teach people with chronic aspecific psychosomatic symptoms (CAPS) to react
      adequately to disturbances of the balance between a daily workload and the
      capacity to deal with it. The long-term effects of the program in improving the
      balance between work stress and recovery are presented in this study. The
      intervening effect of 'improved balance' on quality of life is also analysed.
      METHODS: A pre-post design is used with post-measures at 2 and 12 months after
      the program, without controls (n = 122). Mean age is 42.5 years (S.D. = 9.0) and
      60% of participants are female. RESULTS: The results show participants become
      more active physically and socially, and at the same time take the opportunity to
      recover. There was a difference measured in changing balance for participants who
      are fully employed and participants who are not working or are working part-time
      due to health problems: the second group reintegrated into work, the first group
      spent more time socialising inside the family. Personal goals are realised by 85%
      of the participants. Realising personal goals and becoming more active is a
      mediating factor for increasing quality of life. The majority of the measured
      changes can be interpreted as clinically relevant outcomes with medium-to-large
      effect sizes. Spouses of the participants also confirm these effects. DISCUSSION
      AND CONCLUSION: Evaluation of the BAP gives evidence to conclude that this
      program leads to long-term effects in CAPS. Participants react more adequately to
      disturbances between daily workload and the capacity to deal with this load. Two
      and 12 months after the 3-day program, they changed their behaviour to a more
      active lifestyle and increased self-management in coping with stress and
      psychosomatic symptoms. PRACTICE IMPLICATIONS: By paying more attention to the
      balance between work stress and recovery, patient educators may be able to
      increase their effectiveness. Personal goal realization can be effective in
      guiding people by getting them out of the negative spiral.

PMID- 16442455
TI  - 'What's in a face?' The role of doctor ethnicity, age and gender in the formation
      of patients' judgements: an experimental study.
AB  - BACKGROUND: Research has shown that doctor's make judgements about patients on
      the basis of their demographic characteristics. Little is known about how
      patients judge their doctors. AIM: The present study aimed to explore the impact
      of a doctor's ethnicity, age and gender on patients' judgements in the setting of
      a general practice consultation. METHODS: The study involved an experimental
      factorial design using vignettes with patients receiving one of eight photos of a
      doctor who varied in terms of ethnic group (Asian versus White), age (older
      versus younger) and gender (male versus female). Six general practices in South
      West London took part and 309 patients (response rate = 77%) rated the doctor in
      terms of the expected behaviour of the doctor, the expected behaviour of the
      patient and the patient ease with the doctor. RESULTS: The results showed that in
      terms of the impact of ethnic group, the Asian doctor and White doctor received
      comparable ratings for most questions; however, the Asian doctor was rated as
      being more likely to explore emotional aspects of health than the White doctor.
      Differences for age and gender were more profound. In particular, both the
      younger doctor and the female doctor were judged to have a better personal
      manner, better technical skills, better explanation skills, to be more likely to
      explore emotional aspects of health and empower the patient. Patients also stated
      that they were more likely to have faith in their diagnoses, advice and to comply
      with treatment and preferred both the younger and female doctors for a physical
      examination. In addition, younger doctors were deemed to be more likely to refer
      a patient to see a hospital specialist and female doctors were seen to be more
      likely to suggest complementary therapy. CONCLUSION: A doctor's age and gender
      have a stronger impact on a patient's judgements than their ethnicity.

PMID- 16442456
TI  - Introducing Arabic language patient education materials in Jordan.
AB  - OBJECTIVES: To describe the development and introduction of patient education
      materials in a primary care setting in Jordan. METHODS: During the 2003-2004
      academic year, the authors collaborated to produce more than 25 Arabic language
      written patient education materials designed to conform to cultural and social
      norms and expectations. RESULTS: Patient education materials were frequently
      shared with friends and family members. Readability of materials was judged to be
      excellent when materials were presented at approximately a sixth grade reading
      level. CONCLUSIONS: Patient education materials are greatly needed in Jordan. A
      thorough understanding of the culture facilitates alignment of the health message
      with social norms and establishment of credibility with the target audience. The
      materials developed were well received by patients and physicians. PRACTICE
      IMPLICATIONS: The routine integration of patient education into all medical
      consultations in Jordan is an important goal. Practice based research will be
      vital in identifying and eliminating barriers to the introduction of patient
      education in the clinical setting.

PMID- 16442457
TI  - Social consequences of HIV-positive women's participation in prevention of mother
      to-child transmission programmes.
AB  - Approximately two-third of the worlds HIV/AIDS cases are found in sub-Saharan
      Africa. The rate of mother-to-child-transmission (MTCT) has been found to lie
      between 15 and 40%. The aim of this study was to explore the social consequences
      affecting the experience HIV-positive women have when taking part in a prevention
      of mother-to-child-transmission programme (PMTCT). Few studies have investigated
      this earlier. A cross section of 52 participating women enrolled into a PMTCT
      programme were randomly selected and interviewed, using a structured
      questionnaire. There were three main findings. The most important consequence of
      participating was the difficulty associated with the breast-feeding issue. For
      the women who because of a wish to prevent MTCT are employing formula feeding,
      this causes suspicion and prejudice amongst people in the local community. Few
      people influence a woman's decision to take part, as they tend to keep their HIV
      status to themselves. More information to the general public about HIV and PMTCT
      programmes will enhance acceptance to HIV, and generate an environment conducive
      towards participation in PMTCT programmes.

PMID- 16442458
TI  - A therapeutic education programme for diabetic children: recreational, creative
      methods, and use of puppets.
AB  - Patient education is an important aspect of care to young diabetic children. The
      use of playthings and recreational activities is an effective way to help
      children develop harmoniously by integrating the paradox of having to become
      compliant with treatment and medication while becoming autonomous in life. This
      paper presents the evaluation of a therapeutic education programme which was
      attended by 14 young diabetic patients aged 10-12. In order to take into account
      the learning capacities and strategies linked to the children's age and
      development stage, the programme's methods were mainly interactive and
      recreational. In particular, puppets were used as a means to enable the children
      to express themselves on different aspects of diabetes-related difficulties in
      their everyday life. The results of the study show that recreational methods and
      tools can effectively be implemented into therapeutic patient education
      programmes so as to enable children to develop various treatment-related skills.
      As far as the psychosocial skill of expressing one's difficulties and emotions is
      concerned, the use of puppets was found to be an effective means to facilitate
      the development of such a skill. Moreover, puppets were found to have a
      projective and transactional function that allowed children to make decisions and
      react autonomously, and thus regain control on situations in which they had
      previously felt disempowered.

PMID- 16442459
TI  - Determinants of satisfaction with the health state of the facial skin in patients
      undergoing surgery for facial basal cell carcinoma.
AB  - OBJECTIVE: The main objective of the study was to assess which health beliefs
      predict and explain satisfaction with the facial health state of patients
      undergoing surgery for basal cell carcinoma. METHODS: Data were collected by
      administering a newly developed questionnaire pre-operatively and 6 months post
      operatively (n = 222). RESULTS: Results show that satisfaction as measured by
      post-operative worrying, susceptibility and fear of developing a new BCC at other
      facial sites can be predicted by pre-operative health beliefs. In addition, some
      patients an increase in perceived susceptibility, fear of recurrence of BCC on
      the same site or fear of developing a new BCC at other facial sites. CONCLUSION:
      Our findings indicate that both pre- and post-operative perceptions predict and
      explain for a substantial part the extent to which patients are satisfied with
      their facial health state 6 months after surgery. PRACTICE IMPLICATIONS:
      Administering a short questionnaire at the start of the treatment period will
      give physicians a better understanding of how patients experience this skin
      disease. It will also help them to adjust information about BCC and its
      consequences to the needs of the patient.

PMID- 16442460
TI  - Perceived body image among African Americans with type 2 diabetes.
AB  - OBJECTIVE: To assess current, desired and best body image in the opposite sex and
      examine correlates of body image dissatisfaction. METHODS: We conducted a cross
      sectional analysis at baseline of 185 (141 women, 44 men) African Americans with
      type 2 diabetes in Project Sugar 1, a randomized controlled trial of primary care
      based interventions to improve diabetic control. RESULTS: Women had a
      significantly lower desired body image compared to their current body image (BMI
      approximately 27.7 versus approximately 35.3). Men preferred a body image for
      women that was similar to the body image that women desired for themselves (BMI
      approximately 28.3 versus approximately 27.7). Significant correlates of body
      image dissatisfaction included self-perception of being overweight and attempting
      weight-loss (P < 0.05). PRACTICAL IMPLICATIONS: Among overweight and obese
      African-American women with diabetes, it is important to first address an
      individual's perceived body image, perceived risk of disease, desired body image,
      and weight-loss perceptions. In addition to the aesthetic benefits of weight
      loss, there is a need to focus on the health benefits in order to intervene among
      African Americans with diabetes.

PMID- 16442461
TI  - Beyond clinical trials and narratives: a participatory action research with
      cancer patient self-help groups.
AB  - The self-help movement in Hong Kong has been gradually gaining its momentum in
      recent years. The primary purpose of the research was to give voice to the
      experiences and views of patients towards cancer care and to influence healthcare
      providers and policy makers to act on patients' agendas. Self-help groups and
      their members are mobilized through the research activities of focus groups,
      interviews and a patient forum to specify and act on their needs. This article
      describes the project and the participatory action research (PAR) strategies in
      the mobilization of, and collaboration with, patient groups in research design,
      data analysis, and dissemination of findings. The implications on healthcare
      practice, particularly within an era of reform and restructuring of the
      healthcare system, are discussed.

PMID- 16442462
TI  - Learned resourcefulness and smoking cessation revisited.
AB  - OBJECTIVE: Even though many young addicted smokers profess a desire to quit,
      majority of them are unsuccessful in their attempts. A major goal was to
      determine whether successful quitters are better equipped cognitively and
      behaviorally to deal with the adverse effects associated with the cessation
      process than unsuccessful quitters, because they possess a larger repertoire of
      learned resourcefulness skills. METHOD: Undergraduate university students,
      consisting of 69 never-smokers, 59 successful quitters and 61 unsuccessful
      quitters, completed Rosenbaum's (1980) Self-Control Schedule assessing one's
      general repertoire of learned resourcefulness skills. Daily smoking rate, age
      started smoking, years smoking, quit attempts, difficulty quitting, quitting
      importance, motivation, self-efficacy and use of smoking self-regulatory
      strategies also were compared for the smoking groups. RESULTS: Never-smokers and
      successful quitters were significantly more resourceful than unsuccessful
      quitters. Even though both smoking groups smoked the same daily rate and started
      smoking at the same age, unsuccessful quitters in comparison to successful
      quitters viewed quitting smoking as less important and as more difficult, were
      more extrinsically motivated to quit, less efficacious, and used fewer self
      regulatory strategies during their quit attempts. DISCUSSION: The discussion
      highlights the prominent role that SCS scores, self-efficacy and especially
      perceived quitting difficulty play in the smoking cessation process. CONCLUSIONS
      AND PRACTICAL IMPLICATIONS: Low resourceful smokers having difficulty quitting
      may find workshops on general life skills beneficial. Concurrently providing them
      with specific smoking cessation strategies may further serve to enhance these
      smokers' self-efficacy.

PMID- 16442463
TI  - Effects of delayed psychosocial interventions versus early psychosocial
      interventions for women with early stage breast cancer.
AB  - OBJECTIVE: The importance of psychosocial counselling after a diagnosis of cancer
      has been acknowledged and many intervention studies have been carried out, with
      the aim to find out which types of intervention are most effective in enhancing
      quality of life in cancer patients. A factor which could be part of effective
      counselling could be the time of offering psychosocial counselling. The aim of
      this study was to research the effect of time of enrolment in a psychosocial
      group intervention on psychosocial adjustment. METHODS: In the present study, 67
      women with early stage breast cancer were randomised in a psychosocial group
      intervention program starting within 4 months after surgery or in the same
      intervention program starting at least 3 months later. RESULTS: The main
      conclusion of this study is that women who started with their intervention early
      were less distressed at 6 months follow-up than women who were in the delayed
      condition. Medical and demographic variables were predictive for some
      psychosocial adjustment indicators, but were not associated with time of
      enrolment. Regardless of time of enrolment, women improved in distress, body
      image and recreational activities, but showed a decrease in social interaction.
      CONCLUSION: Though results are limited, based on these results we suggest that
      psychosocial counselling should be offered as soon after diagnosis or surgery for
      breast cancer. PRACTICE IMPLICATIONS: Women diagnosed with primary breast cancer
      should be able to start with psychological counselling soon after being
      diagnosed, to prevent them from becoming distressed at long term.

PMID- 16442464
TI  - Evaluation of a self-management-based patient education program for the treatment
      and prevention of hypoglycemia-related problems in type 1 diabetes.
AB  - OBJECTIVE: Aim of this study was to investigate the effectiveness of a patient
      education program for the treatment of hypoglycemia-associated problems in type 1
      diabetic inpatients. METHODS: In this observational controlled pre-post study,
      the intervention group (IG; N = 105) participated in the new program, controls
      (control group CG; N = 102) received conventional patient education on
      hypoglycemia. RESULTS: Follow-up data (mean follow-up: 6.63 months) were obtained
      from 177 patients (85.6%). Though severe hypoglycemia also decreased in CG to
      some degree, the decrease in IG was higher than in CG, but fails to reach
      significance between groups. Hypoglycemia awareness remained constant in IG,
      whereas some deterioration was observed in CG (p = 0.06). Prevalence of
      hypoglycemia-related problems decreased in IG, whereas in CG it remained
      constant. No differential effects with regard to psychological well being, fear
      of hypoglycemia and late complications, and control beliefs were observed.
      CONCLUSION: The results suggest that the new intervention program is an effective
      treatment. The effectiveness should be confirmed, however, in a randomized
      controlled trial, also incorporating outpatient settings. PRACTICE IMPLICATIONS:
      A self-management intervention targeting the patients' health beliefs and
      attitudes towards hypoglycemia and their diabetes self-management, rather than
      knowledge-centered patient education, can help to ameliorate or even prevent
      hypoglycemia-associated problems.

PMID- 16442465
TI  - Nurses' recognition and registration of depression, anxiety and diabetes-specific
      emotional problems in outpatients with diabetes mellitus.
AB  - OBJECTIVE: The aim of this study was to investigate how often emotional problems
      were recognized and registered by diabetes nurses. METHODS: We studied medical
      charts and questionnaire data of 112 diabetes patients. The hospital anxiety,
      depression scale and the problem areas in diabetes survey were used to measure
      anxiety, depression and diabetes-specific emotional distress. RESULTS: In
      patients with moderate to severe levels of anxiety or depression, the presence of
      an emotional problem was recorded in the medical chart in 20-25% of the cases.
      The registration-rate of diabetes-specific emotional distress was also found to
      be low, ranging from 0% (treatment-related problems) to 29% (diabetes-related
      emotional problems). CONCLUSION: Registration-rates of emotional problems by
      diabetes nurses were found to be low, but quite similar to detection rates of
      physicians and nurses in studies with non-diabetic samples. PRACTICE
      IMPLICATIONS: These findings suggest that recognition-rates of emotional problems
      in diabetes patients need to be increased. Future studies should investigate
      whether recognition and subsequent treatment of emotional problems in diabetes
      patients can be facilitated by utilizing validated, standardized self-report
      questionnaires.

PMID- 16442466
TI  - A study to investigate the extent of delivery of an intervention in asthma, in a
      UK national community pharmacy chain, using mystery customers.
AB  - OBJECTIVE: The objective of this study was to implement a brief intervention in
      asthma within a UK national pharmacy chain, and through the use of mystery
      customers, measure the extent of delivery of the intervention over a 4-month
      period. METHODS: Mystery customers gathered information on which of the asthma
      intervention questions were asked, and any lifestyle advice that was given.
      Additional information was collected on the type of store they visited and the
      personnel who served them. RESULTS: Mystery customer results indicate delivery
      rates of the intervention between 48.1 and 84.3% across the 4-month assessment
      period. This intervention was delivered by both pharmacists and healthcare staff,
      although the extent and content of delivery varied across the 4 months.
      CONCLUSION: The use of mystery customers has helped to assess the successful take
      up and delivery of this intervention. Based on the learning points gained
      throughout this study, future services can be designed for other condition areas.
      PRACTICE IMPLICATIONS: Each service that is designed needs to be simple to
      implement and deliver, and have the flexibility for pharmacists and staff to
      adapt the services to meet local requirements.

PMID- 16442467
TI  - Shared decision-making in an intercultural context. Barriers in the interaction
      between physicians and immigrant patients.
AB  - OBJECTIVE: The objective of this exploratory paper is to describe several
      barriers in shared decision-making in an intercultural context. METHODS: Based on
      the prevailing literature on intercultural communication in medical settings,
      four conceptual barriers were described. When the conceptual barriers were
      described, they were compared with the results from semi-structured interviews
      with purposively selected physicians (n = 18) and immigrant patients (n = 13).
      Physicians differed in medical discipline (GPs, company doctors, an internist, a
      cardiologist, a gynaecologist, and an intern) and patients had different ethnic
      and immigration backgrounds. RESULTS: The following barriers were found: (1)
      physician and patient may not share the same linguistic background; (2) physician
      and patient may not share similar values about health and illness; (3) physician
      and patient may not have similar role expectations; and (4) physician and patient
      may have prejudices and do not speak to each other in an unbiased manner.
      CONCLUSION: We conclude that due to these barriers, the transfer of information,
      the formulation of the diagnosis, and the discussion of treatment options are at
      stake and the shared decision-making process is impeded. PRACTICE IMPLICATIONS:
      Improving physician's skills to recognize the communication limitations during
      shared decision-making as well as improving the skills to deal with the barriers
      may help to ameliorate shared decision-making in an intercultural setting.

PMID- 16442468
TI  - Best of times and worst of times: the future of psychiatric nursing.

PMID- 16442469
TI  - The evaluation of cognitive-behavioral group therapy on patient depression and
      self-esteem.
AB  - We evaluated the impact of cognitive-behavioral group therapy on the depression
      and self-esteem of clinically depressed patients. This longitudinal study
      involved 26 experimental group patients who received 12 weeks of cognitive
      behavioral group therapy and 25 comparison subjects. Two weeks before the study,
      immediately upon therapy completion, and 1 month later, all the participants
      underwent pretest, posttest, and follow-up, respectively. The experimental group
      patients experienced greater cognitive improvements (i.e., depression relief,
      self-esteem increase) as compared with the comparison group subjects. One month
      after therapy completion, the depressive symptoms and self-esteem of the
      experimental group patients remained slightly but significantly better than those
      of the comparison group subjects.

PMID- 16442470
TI  - Social interaction, premorbid personality, and agitation in nursing home
      residents with dementia.
AB  - Agitation is exhibited by most nursing home residents with dementia and is a risk
      factor for poor health outcomes. Identifying the antecedents of agitation is
      essential for appropriate treatment because interventions require well-defined
      targets. This study explored relationships between level of social interaction
      (high vs. low), the premorbid personality trait of extraversion, and agitation
      using baseline data from a clinical trial that tested the efficacy of activity
      interventions for agitation. Most residents exhibited at least one agitated
      behavior over the 332 observation days. Agitation was significantly greater under
      high social interaction as compared with low social interaction (P < .0001)
      regardless of the extraversion score.

PMID- 16442471
TI  - The BE SMART trauma reframing psychoeducation program.
AB  - Despite the human capacity to survive and adapt, traumatic experiences can cause
      alterations in health, attitudes and behaviors, environmental and interpersonal
      functioning, and spiritual balance such that the memory of an event or a set of
      events taints all other experiences. The BE SMART (Become Empowered: Symptom
      Management for Abuse and Recovery from Trauma) group psychoeducation program is a
      12-week course designed for both men and women to learn wellness coping
      principles in recovering from the aftermaths of trauma and abuse. The course is
      based on the Murphy-Moller Wellness Model [Murphy, M. F., & Moller, M. D. (1996).
      The Three R's Program: A Wellness Approach to Rehabilitation of Neurobiological
      Disorders. The International Journal of Psychiatric Nursing Research, 3(1), 308
      317] and the Trauma Reframing Therapy [Rice, M. J., & Moller, M. D. (2003).
      Wellness Outcomes of Trauma Psychoeducation. Podium presentation at the 2003
      Meeting of the American Psychiatric Nurses Association. Atlanta, Georgia.
      October].

PMID- 16442472
TI  - Why are young college women not using condoms? Their perceived risk, drug use,
      and developmental vulnerability may provide important clues to sexual risk.
AB  - BACKGROUND: Young multiethnic college women (YMCW) are at risk for STDs and HIV
      secondary to high-risk sexual behaviors that are related to developmental issues
      such as invincibility, low perceived risk, and substance use. METHOD: One hundred
      YMCW on a southern California university campus completed surveys that examined
      variables that impacted their sexual risk. RESULTS: The study yielded many
      significantly correlated variables. Women with low perceived risk, lower use of
      drugs and alcohol, and who had parental involvement had lower sexual behavior
      risk. Women that were sexually assertive, had intentions to use condoms, and did
      not use substances used condoms more often. Older students in advanced grades who
      had steady partners used substances less and had decreased sexual risk, however,
      they experienced partner resistance to condoms, which canceled out any reduced
      risk. In a multiple regression analysis, condom use intention and substance use
      predicted condom use, perceived risk and substance use predicted sexual behavior
      risk. White women had significantly higher substance use, perceived sexual risk,
      and sexual behavior risk than did Latinas and African Americans. CONCLUSIONS:
      Despite their assertiveness and intentions, many participants had multiple sexual
      partners, and 64% of the YMCW were inconsistent condom users. Despite knowing the
      elevated risks, 52% used drugs and alcohol during sex. Negative attitudes (61%)
      about condoms were also demonstrated as a key factor in the lack of condom use.

PMID- 16442473
TI  - Mastery, burden, and areas of concern among family caregivers of mentally ill
      persons.
AB  - In an era of limited resources for mental health care, family interventions need
      to target areas where they are responsive to families' expressed needs. Although
      family burden has been documented, less is known about the areas of concern that
      families feel they need direct assistance with, to be effective caregivers.
      Telephone interviews were conducted with 30 family members of mentally ill
      relatives. Burden, sense of mastery, and contexts of caregiving were assessed.
      Open-ended questions elicited further understandings of caregiving concerns. The
      most frequently identified burden was "worry about the future." The greatest
      concern was "dealing with sadness and grief." Recommendations for assessing
      family concerns are presented.

PMID- 16442474
TI  - And it can go on and on and on...

PMID- 16442475
TI  - Opioid rotation to methadone at home.

PMID- 16442476
TI  - Re: research in palliative care.

PMID- 16442477
TI  - Screening for depression in terminally ill cancer patients in Japan.
AB  - This study attempted to assess the performance of several screening instruments
      for adjustment disorders (ADs) and major depression (MD) among terminally ill
      Japanese cancer patients. Two hundred and nine consecutive patients were assessed
      for ADs and MD using a structured clinical interview at the time of their
      registration with a palliative care unit, and two single-item interviews ("Are
      you depressed?" and "Have you lost interest?") and the Hospital Anxiety and
      Depression Scale (HADS) were administered. Screening performance was investigated
      by calculating sensitivity, specificity, the positive predictive value, negative
      predictive value, likelihood ratio, and stratum-specific likelihood ratios. When
      the screening target included both an AD and MD, the HADS is a more useful
      screening method than the single-item interviews. Regarding screening for MD,
      both single-item interviews and the HADS possess useful screening performance.
      Different screening instruments may be recommended depending on the depressive
      disorders and specific populations.

PMID- 16442478
TI  - Validation of the Malay Brief Pain Inventory questionnaire to measure cancer
      pain.
AB  - The original version of the Brief Pain Inventory (BPI) was translated into a
      Malay version by the standard procedure and was then evaluated for its
      psychometric properties. Of 119 eligible patients, a total of 113 (95%) agreed to
      participate in this study. Ages ranged from 18 to 76 years and interviews were
      conducted between August, 2004 and November, 2004. The pain intensity items
      demonstrated high loading with one factor, whereas the pain interference items
      were loaded on another factor. Two factors explained 62% of the variance.
      Compared to the Karnofsky Performance Scale, the pain intensity scales had a
      moderate negative (Pearson's) correlation (-0.520, P < 0.001) and the pain
      interference scales had a high negative correlation (-0.732, P < 0.001), showing
      good concurrent validity. The coefficient alpha of both subscales demonstrated
      good internal consistency of the items. The intraclass correlation coefficient
      for the test-retest stability was 0.61 for the pain intensity scale and 0.88 for
      the pain interference scale. The Malay version of the BPI is a reliable and valid
      instrument for cancer pain assessment and is comparable with the original version
      of the BPI in terms of structure and psychometric properties.

PMID- 16442479
TI  - Using the symptom monitor in a randomized controlled trial: the effect on symptom
      prevalence and severity.
AB  - This randomized controlled trial investigated the effect of reporting physical
      symptoms by using a systematic symptom monitoring instrument, the Symptom
      Monitor, on symptom prevalence and severity among patients with cancer in the
      palliative phase. The overall objective was to achieve symptom relief through
      systematic and regular symptom reporting by patients themselves. One hundred
      forty-six patients with cancer in the palliative phase were randomized to either
      the intervention group (n = 69 with Symptom Monitor) or the control group (n = 77
      without Symptom Monitor). Ten physical symptoms with regard to prevalence and
      severity were monitored. After 2 months, the prevalence of symptoms was lower in
      the intervention group compared to the control group (prevalent differences 2.1
      24.3%) for 9 out of 10 symptoms (except coughing). The intervention group scored
      a statistically significantly lower prevalence in constipation and vomiting
      (prevalence differences 24.3% and 18.0%, respectively). In four symptoms
      (fatigue, lack of appetite, shortness of breath, and nausea), the intervention
      group had a lower, although not statistically significant, severity score (median
      differences 0.5-1). In four symptoms (pain, coughing, sleeplessness, and
      diarrhea), the severity score was the same in both groups (medians 2-4). In two
      symptoms (constipation and vomiting), the severity score was lower in the control
      group (median differences -1 and -2). A comparison between the study groups on
      improved, deteriorated, or steady-state cases showed that the severity score had
      deteriorated less for 8 out of 10 symptoms in a larger proportion of patients in
      the intervention group. Although statistical significance was not reached, the
      prevalence as well as severity of symptoms in the palliative phase of cancer can
      be influenced by using the Symptom Monitor.

PMID- 16442480
TI  - Symptom assessment in community-dwelling older adults with advanced chronic
      disease.
AB  - Brief symptom instruments are designed to assess symptoms while maintaining low
      respondent burden, but they may omit important information. Our objective was to
      determine whether a representative brief symptom instrument effectively captures
      the full symptom experience of older adults with advanced diseases. In this cross
      sectional study, we interviewed 90 community-dwelling adults with cancer,
      congestive heart failure, or chronic obstructive pulmonary disease regarding the
      presence of symptoms in the prior 24 hours. Participants rated the intensity and
      bothersome nature of 15 symptoms--10 symptoms were included in the Edmonton
      Symptom Assessment Scale (ESAS) plus 5 supplemental symptoms. Participants
      reported similar proportions of ESAS and supplemental symptoms. Intensity and
      "bothersomeness" ratings frequently differed. Brief symptom instruments only
      provide a limited assessment of the respondent's symptom experience. The benefit
      obtained from incorporating both the intensity and bothersome nature of a longer
      list of symptoms may outweigh the potential increase in respondent burden.

PMID- 16442481
TI  - Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea
      perception in patients with advanced cancer.
AB  - The mainstay of dyspnea palliation remains altering its central perception.
      Morphine is the main drug and anxiolytics have a less established role. This
      trial assessed the role of midazolam as adjunct therapy to morphine in the
      alleviation of severe dyspnea perception in terminally ill cancer patients. One
      hundred and one patients with severe dyspnea were randomized to receive around
      the-clock morphine (2.5 mg every 4 hours for opioid-naive patients or a 25%
      increment over the daily dose for those receiving baseline opioids) with
      midazolam rescue doses (5 mg) in case of breakthrough dyspnea (BD) (Group Mo);
      around-the-clock midazolam (5 mg every 4 hours) with morphine rescues (2.5 mg) in
      case of BD (Group Mi); or around-the-clock morphine (2.5 mg every 4 hours for
      opioid-naive patients or a 25% increment over the daily dose for those receiving
      baseline opioids) plus midazolam (5 mg every 4 hours) with morphine rescue doses
      (2.5 mg) in case of BD (Group MM). All drugs were given subcutaneously in a
      single-blinded way. Thirty-five patients were entered in Group Mo, 33 entered in
      Mi, and 33 entered in MM. At 24 hours, patients who experienced dyspnea relief
      were 69%, 46%, and 92% in the Mo, Mi, and MM groups, respectively (P = 0.0004 and
      P = 0.03 for MM vs. Mi and MM vs. Mo, respectively). At 48 hours, those with no
      dyspnea relief (no controlled dyspnea) were 12.5%, 26%, and 4% for the Mo, Mi,
      and MM groups, respectively (P = 0.04 for MM vs. Mi). During the first day,
      patients with BD for the groups Mo, Mi, and MM were 34.3%, 36.4%, and 21.2%,
      respectively (P = NS or not significant), whereas during the second day, these
      percentages were 38%, 38.5%, and 24%, respectively (P = NS). The data demonstrate
      that the beneficial effects of morphine in controlling baseline levels of dyspnea
      could be improved with the addition of midazolam to the treatment.

PMID- 16442482
TI  - The validity and utility of the BPI interference measures for evaluating the
      impact of osteoarthritic pain.
AB  - The psychometric properties of the Brief Pain Inventory (BPI), a widely used
      measure of pain and its impact on functioning, were assessed using data from two
      clinical trials of controlled-release oxycodone in osteoarthritis (OA) patients.
      Specifically, the pain-related functional interference subscale and the sleep
      item from that subscale were examined. In Study 1 (n = 133), "night awakenings
      with pain" was positively correlated with the BPI interference score and sleep
      item and both correlated negatively with "quality of sleep." In Study 2 (n =
      107), pain experienced "at night while in bed" correlated higher with sleep
      interference than with the BPI interference subscale. Intraclass correlations
      denoted adequate test-retest reliability; moderate-to-large Guyatt's statistics
      provided evidence of responsiveness. These analyses address a gap in the
      literature regarding the psychometric properties of the BPI interference measures
      in noncancer pain patients, confirming their reliability, validity, and
      responsiveness as potential endpoints in trials of pain medications involving
      patients with OA.

PMID- 16442483
TI  - A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease,
      chronic obstructive pulmonary disease and renal disease.
AB  - Little attention has been paid to the symptom management needs of patients with
      life-threatening diseases other than cancer. In this study, we aimed to determine
      to what extent patients with progressive chronic diseases have similar symptom
      profiles. A systematic search of medical databases (MEDLINE, EMBASE, and
      PsycINFO) and textbooks identified 64 original studies reporting the prevalence
      of 11 common symptoms among end-stage patients with cancer, acquired
      immunodeficiency syndrome (AIDS), heart disease, chronic obstructive pulmonary
      disease, or renal disease. Analyzing the data in a comparative table (a grid), we
      found that the prevalence of the 11 symptoms was often widely but homogeneously
      spread across the five diseases. Three symptoms-pain, breathlessness, and fatigue
      were found among more than 50% of patients, for all five diseases. There appears
      to be a common pathway toward death for malignant and nonmalignant diseases. The
      designs of symptom prevalence studies need to be improved because of
      methodological disparities in symptom assessment and designs.

PMID- 16442484
TI  - Hypnosis for procedure-related pain and distress in pediatric cancer patients: a
      systematic review of effectiveness and methodology related to hypnosis
      interventions.
AB  - The aim of this study was to systematically review and critically appraise the
      evidence on the effectiveness of hypnosis for procedure-related pain and distress
      in pediatric cancer patients. A comprehensive search of major biomedical and
      specialist complementary and alternative medicine databases was conducted.
      Citations were included from the databases' inception to March 2005. Efforts were
      made to identify unpublished and ongoing research. Controlled trials were
      appraised using predefined criteria. Clinical commentaries were obtained for each
      study. Seven randomized controlled clinical trials and one controlled clinical
      trial were found. Studies report positive results, including statistically
      significant reductions in pain and anxiety/distress, but a number of
      methodological limitations were identified. Systematic searching and appraisal
      has demonstrated that hypnosis has potential as a clinically valuable
      intervention for procedure-related pain and distress in pediatric cancer
      patients. Further research into the effectiveness and acceptability of hypnosis
      for pediatric cancer patients is recommended.

PMID- 16442485
TI  - Symptom cluster research: conceptual, design, measurement, and analysis issues.
AB  - Cancer patients may experience multiple concurrent symptoms caused by the cancer,
      cancer treatment, or their combination. The complex relationships between and
      among symptoms, as well as the clinical antecedents and consequences, have not
      been well described. This paper examines the literature on cancer symptom
      clusters focusing on the conceptualization, design, measurement, and analytic
      issues. The investigation of symptom clustering is in an early stage of testing
      empirically whether the characteristics defined in the conceptual definition can
      be observed in cancer patients. Decisions related to study design include sample
      selection, the timing of symptom measures, and the characteristics of symptom
      interventions. For self-report symptom measures, decisions include symptom
      dimensions to evaluate, methods of scaling symptoms, and the time frame of
      responses. Analytic decisions may focus on the application of factor analysis,
      cluster analysis, and path models. Studying the complex symptoms of oncology
      patients will yield increased understanding of the patterns of association,
      interaction, and synergy of symptoms that produce specific clinical outcomes. It
      will also provide a scientific basis and new directions for clinical assessment
      and intervention.

PMID- 16442486
TI  - Contribution of cell surface protein antigen PAc of Streptococcus mutans to
      bacteremia.
AB  - Streptococcus mutans, a major cariogenic bacterium, is occasionally isolated from
      the blood of patients with bacteremia and infective endocarditis. Mutant strains
      of S. mutans MT8148, defective in the major surface proteins glucosyltransferase
      (GTF) B-, C-, and D-, and protein antigen c (PAc), were constructed by
      insertional inactivation of each respective gene with an antibiotic resistant
      cassette. Susceptibility to phagocytosis was determined by analyses of
      interactions of the bacteria with human polymorphonuclear leukocytes, and the PAc
      defective mutant strain (PD) showed the lowest rate of phagocytosis. Further,
      when PD and MT8148 were separately injected into the jugular veins of Sprague
      Dawley rats, PD was recovered in significantly larger numbers and for a longer
      duration, and caused more severe systemic inflammation than MT8148, indicating
      that S. mutans PAc is associated with its systemic virulence in blood. Next, 100
      S. mutans clinical isolates from 100 Japanese children and adolescents were
      analyzed by Western blotting using antisera raised against recombinant PAc,
      generated based on the pac sequence of MT8148. Four of the 100 strains showed no
      positive band and each exhibited a significantly lower phagocytosis rate than
      that of 25 randomly selected clinical strains (P < 0.01). In addition, three of
      the 100 strains possessed a lower molecular weight PAc and a significantly lower
      rate of phagocytosis than the 25 reference strains (P < 0.05). These results
      suggest that S. mutans PAc may be associated with phagocytosis susceptibility to
      human polymorphonuclear leukocytes, with approximately 7% of S. mutans clinical
      isolates possible high-risk strains for the development of bacteremia.

PMID- 16442487
TI  - Predicting the frequency of median barrier crashes on Pennsylvania interstate
      highways.
AB  - Median barrier warrant criteria were developed in the 1970s and generally remain
      unchanged today. Vehicle travel, including both traffic volumes and operating
      speeds, have increased over this same time period. Encroachments into the median,
      and subsequent collisions with vehicles traveling in the opposite travel lanes,
      result in high severity crashes. Median barrier is typically used to prevent
      cross-median crashes; median barrier selection is based on median width and
      traffic volumes. Quantifiable information regarding the effects of median barrier
      installation and its placement on crash frequency is limited. This paper
      investigates median barrier crash frequency on Pennsylvania Interstate highways,
      including separate models for the Turnpike and all other Interstate-designated
      highways. Negative binomial regression models were used to develop predictive
      crash frequency tools. Traffic volume, horizontal alignment, interchange ramp
      presence, and median barrier offset distance from the travel lanes were used to
      estimate median barrier crash frequency. The analytical methodology developed in
      this research can be used, in concert with other prediction models, to assess the
      consequences of median barrier placement decisions.

PMID- 16442488
TI  - Application of the ferrous oxidation-xylenol orange assay for the screening of 5
      lipoxygenase inhibitors.
AB  - 5-Lipoxygenase (5-LO) is the key enzyme involved in leukotriene synthesis and its
      improper regulation is implicated in several inflammatory diseases. A rapid and
      sensitive assay for 5-LO activity suitable for high-throughput format is not yet
      available. In this study, we examined whether the ferrous oxidation-xylenol
      orange (FOX) assay could be applicable for the high-throughput screening of 5-LO
      inhibitors. Using insect cell lysates overexpressing rat 5-LO, the effects of
      cofactors of 5-LO such as ATP, Ca2+, and L-alpha-phosphatidylcholine (PC) on the
      color development of FOX reagents were investigated. ATP quenched substantially
      color development by hydroperoxide, an intermediate of 5-LO reaction, and an
      optimum concentration of ATP with little interference was determined as 20
      microM. Ethylenediaminetetraacetate (0.4 mM) also affected the complex formation
      with FOX reagents. On the other hand, neither Ca2+ nor PC influenced complex
      formation with FOX reagents. Under optimized assay conditions, zileuton, a 5-LO
      specific inhibitor, exhibited inhibitory potency (IC50 values of 0.1-0.2 microM)
      similar to that determined by the conventional spectrophotometric assay. Taken
      together, this study shows that the FOX assay with some modifications can be
      employed for high-throughput assay format for the measurement of 5-LO activity at
      the stage of primary screening.

PMID- 16442489
TI  - A nonradioisotope, enzymatic assay for 2-deoxyglucose uptake in L6 skeletal
      muscle cells cultured in a 96-well microplate.
AB  - A nonradioisotope, 96-well-microplate assay to evaluate glucose uptake activity
      in cultured cells has been developed. 2-Deoxyglucose (2DG) was detected by
      measuring a potent fluorophore, resorufin, generated after incubation with a
      single assay solution containing hexokinase, adenosine 5'-triphosphate, glucose 6
      phosphate dehydrogenase, beta-nicotineamide adenine dinucleotide phosphate,
      diaphorase, and resazurin. This amplifying detection system could detect the
      fluorescence intensity induced by uptake of 2DG into L6 skeletal muscle cells,
      even at the level of cells cultivated in individual wells in a 96-well
      microplate. Using this assay system, the effects of insulin, cytochalasin B
      (hexose uptake inhibitor), LY294002 (inhibitor of glucose transporter
      translocation), and pioglitazone hydrochloride (insulin-sensitizing agent) on 2DG
      uptake into L6 myotubes could be assessed clearly. Therefore, our simple method
      may be useful for in vitro high-throughput screening and for evaluating
      regulators of glucose uptake.

PMID- 16442490
TI  - A DNA and histone immobilization method to study DNA-histone interactions by
      surface plasmon resonance.

PMID- 16442491
TI  - Non-cross-linking gold nanoparticle aggregation for sensitive detection of single
      nucleotide polymorphisms: optimization of the particle diameter.

PMID- 16442492
TI  - [Superior mesenteric artery syndrome: a case report].
AB  - Superior mesenteric artery syndrom is a condition triggered by the compression of
      the third portion of the duodenum between the superior mesenteric artery and the
      aorta. OBSERVATIONS: A twenty-one year old woman with a significant past history
      of neurological disease was referred for bilious vomiting and epigastric pain.
      The diagnosis of superior mesenteric artery syndrom was established by abdominal
      CT-scan. A laterolateral duodenojejunostomy was performed by laparotomy. After
      six months follow-up, this patient was asymptomatic. CONCLUSION: Superior
      mesenteric artery syndrom can be easily diagnosed by abdominal CT-scan. Diagnosis
      and management of this infrequent syndrom are reviewed.

PMID- 16442493
TI  - How do designers represent to themselves the users' needs?
AB  - This paper reports on an ergonomic study carried out during the design of a
      cutting machine-tool for the composite material in carbody parts casting. During
      this design process, the users' needs were inferred by the designers on the basis
      of their own mental representations of the use of the new device. These
      representations of the users' needs, correct or false, play a decisive role in
      the choice of a solution. The aim of the study is to identify their
      particularity. Analyzing the design meetings, we have highlighted that users are
      considered either as subsystems or basic design principles or elements of an
      imagined scenario. We have shown that these representations are linked to the
      types of meetings held during the design process. Accordingly, a diversification
      of the types of meetings should be promoted by the project leader, so that
      designers extend their points of view of the operators.

PMID- 16442494
TI  - Match between school furniture dimensions and children's anthropometry.
AB  - The purpose of the study was to examine whether school furniture dimensions match
      children's anthropometry. Children aged 6-18 years (n=274), divided into 3 groups
      on the basis of the used furniture size, were subjected into anthropometric
      measurements (shoulder, elbow, knee and popliteal height, buttock-popliteal
      length and hip breadth). Combinational equations defined the acceptable furniture
      dimensions according to anthropometry and match percentages were computed,
      according to either the existing situation--where children use the size assigned
      for their grade--or assuming that they could use the most appropriate of the
      sizes available. Desk and seat height were bigger than the accepted limits for
      most children (81.8% and 71.5%, respectively), while seat depth was appropriate
      for only 38.7% of children. In conclusion, the assumption that children could use
      the most appropriate yet available size significantly improved the match,
      indicating that the limited provision of one size per cluster of grades does not
      accommodate the variability of anthropometry even among children of the same age.

PMID- 16442495
TI  - On the interaction site of serine acetyltransferase in the cysteine synthase
      complex from Escherichia coli.
AB  - Cysteine synthase from Escherichia coli is a bienzyme complex comprised of serine
      acetyltransferase (SAT) and O-acetylserine sulfhydrylase A. The site of
      interaction of a SAT molecule was investigated by gel chromatography and surface
      plasmon technique using various mutant-type SATs, to better understand the
      mechanism involved in complex formation. The C-terminus of SAT, Ile 273, along
      with Glu 268 and Asp 271, was found to be essential for complex formation. The
      effects of O-acetyl-L-serine and sulfide on the affinity for the complex
      formation were also studied using a surface plasmon technique.

PMID- 16442496
TI  - Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC.
AB  - Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory
      effects. Additionally, fenofibrate has been demonstrated to upregulate
      endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has
      been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular
      endothelium-derived nitric oxide (NO) production. We report here that fenofibrate
      activates AMPK and increases eNOS phosphorylation and NO production in human
      umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate
      increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate
      simultaneously increased eNOS phosphorylation and NO production. Inhibitors of
      protein kinase A and phosphatidylinositol 3-kinase failed to suppress the
      fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643
      activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without
      requiring any transcriptional activities. These results indicate that fenofibrate
      stimulates eNOS phosphorylation and NO production through AMPK activation, which
      is suggested to be a novel characteristic of this agonist and unrelated to its
      effects on peroxisome proliferator-activated receptor alpha.

PMID- 16442497
TI  - SnoN co-repressor binds and represses smad7 gene promoter.
AB  - SnoN and Ski oncoproteins are co-repressors for Smad proteins and repress TGF
      beta-responsive gene expression. The smad7 gene is a TGF-beta target induced by
      Smad signaling, and its promoter contains the Smad-binding element (SBE) required
      for a positive regulation by the TGF-beta/Smad pathway. SnoN and Ski co
      repressors also bind SBE but regulate negatively smad7 gene. Ski along with Smad4
      binds and represses the smad7 promoter, whereas the repression mechanism by SnoN
      is not clear. Ski and SnoN overexpression inhibits smad7 reporter expression
      induced through TGF-beta signaling. Using chromatin immunoprecipitation assays,
      we found that SnoN binds smad7 promoter at the basal condition, whereas after a
      short TGF-beta treatment for 15-30 min SnoN is downregulated and no longer bound
      smad7 promoter. Interestingly, after a prolonged TGF-beta treatment SnoN is
      upregulated and returns to its position on the smad7 promoter, functioning
      probably as a negative feedback control. Thus, SnoN also seems to regulate
      negatively the TGF-beta-responsive smad7 gene by binding and repressing its
      promoter in a similar way to Ski.

PMID- 16442498
TI  - Human adipose-derived stem cells display myogenic potential and perturbed
      function in hypoxic conditions.
AB  - Here, we enriched a human cell population from adipose tissue that exhibited both
      mesenchymal plasticity, self-renewal capacity, and a cell-surface marker profile
      indistinguishable from that of bone marrow-derived mesenchymal stem cells. In
      addition to adipogenic and osteogenic differentiation, these adipose-derived stem
      cells displayed skeletal myogenic potential when co-cultured with mouse skeletal
      myocytes in reduced serum conditions. Physical incorporation of stem cells into
      multinucleated skeletal myotubes was determined by genetic lineage tracing,
      whereas human-specific antibody staining was employed to demonstrate functional
      contribution of the stem cells to a myogenic lineage. To investigate the effects
      of hypoxia, cells were maintained and differentiated at 2% O(2). In contrast with
      reports on bone marrow-derived stem cells, both osteogenic and adipogenic
      differentiation were significantly attenuated. In summary, the relative
      accessibility of adipose-derived mesenchymal stem cells from human donors
      provides opportunity for molecular investigation of mechanistic dysfunction in
      disease settings and may introduce new prospects for cell-based therapy.

PMID- 16442499
TI  - Study of the ATP-binding site of helicase IV from Escherichia coli.
AB  - Helicases contain conserved motifs involved in ATP/magnesium/nucleic acid binding
      and in the mechanisms coupling nucleotide hydrolysis to duplex unwinding. None of
      these motifs are located at the adenine-binding pocket of the protein. We show
      here that the superfamily I helicase, helicase IV from Escherichia coli, utilizes
      a conserved glutamine and conserved aromatic residue to interact with ATP. Other
      superfamily I helicases such as, UvrD/Rep/PcrA also possess these residues but in
      addition they interact with adenine via a conserved arginine, which is replaced
      by a serine in helicase IV. Mutation of this serine residue in helicase IV into
      histidine or methionine leads to proteins with unaffected ATPase and DNA-binding
      activities but with low helicase activity. This suggests that residues located at
      the adenine-binding pocket, in addition to be involved in ATP-binding, are
      important for efficient coupling between ATP hydrolysis and DNA unwinding.

PMID- 16442500
TI  - Contribution of inducible nitric oxide synthase and cyclooxygenase-2 to apoptosis
      induction in smooth chorion trophoblast cells of human fetal membrane tissues.
AB  - We examined the contribution of apoptosis- and oxidative stress-associated genes
      to apoptosis induction in trophoblast cells of human fetal membrane tissues
      undergoing apoptosis during in vitro incubation. RT-PCR analyses demonstrated an
      increased level of HO-1, Mn-SOD, Cox-2, iNOS, TNFalpha, TNFR1, IL-1beta, IL-6,
      Bax, Bak, and Bad gene expression, while Bcl-2 mRNA expression level decreased.
      Western blot analyses demonstrated an increase in iNOS, Cox-2, and HO-1 protein
      levels; a decrease in pro-caspase-3 and 9, proform-PARP, and Apaf-1 protein
      levels; a leakage of cytochrome c from the mitochondria. An antioxidative
      reagent, general and selective Cox-2 inhibitors, and an iNOS inhibitor suppressed
      in vitro progression of the apoptosis. Furthermore, an NO donor reagent induced
      apoptosis in primary cultured trophoblast cells. Therefore, we concluded that the
      induction of apoptosis in the smooth chorion trophoblasts is mediated through
      oxidative stress induction followed by mitochondria damage, suggesting that iNOS
      and Cox-2 play an important role in the apoptosis induction in trophoblasts of
      human fetal membrane tissues.

PMID- 16442501
TI  - Angiotensin II inhibits inward rectifier K+ channels in rabbit coronary arterial
      smooth muscle cells through protein kinase Calpha.
AB  - We investigated the effects of the vasoconstrictor angiotensin (Ang) II on the
      whole cell inward rectifier K(+) (Kir) current enzymatically isolated from small
      diameter (<100 microm) coronary arterial smooth muscle cells (CASMCs). Ang II
      inhibited the Kir current in a dose-dependent manner (half inhibition value: 154
      nM). Pretreatment with phospholipase C inhibitor and protein kinase C (PKC)
      inhibitors prevented the Ang II-induced inhibition of the Kir current. The PKC
      activator reduced the Kir currents. The inhibitory effect of Ang II was reduced
      by intracellular and extracellular Ca(2+) free condition and by Go6976, which
      inhibits Ca(2+)-dependent PKC isoforms alpha and beta. However, the inhibitory
      effect of Ang II was unaffected by a peptide that selectively inhibits the
      translocation of the epsilon isoform of PKC. Western blot analysis confirmed that
      PKCalpha, and not PKCbeta, was expressed in small-diameter CASMCs. The Ang II
      type 1 (AT(1))-receptor antagonist CV-11974 prevented the Ang II-induced
      inhibition of the Kir current. From these results, we conclude that Ang II
      inhibits Kir channels through AT(1) receptors by the activation of PKCalpha.

PMID- 16442502
TI  - Cloning and expression of human mitogen-activated protein kinase kinase 7gamma1.
AB  - Mitogen-activated protein kinase kinase 7 (MKK7) is a direct activator of the
      mitogen-activated protein kinase family member c-Jun N-terminal kinase (JNK).
      MKK7 activates JNK via phosphorylation of a threonine and tyrosine residue in a
      Thr-Pro-Tyr motif within kinase subdomain VIII. To date at least six different
      isoforms of murine MKK7 have been identified. However, only three isoforms of
      human MKK7 have been reported. We report here the cloning of hMKK7gamma1, the
      human homolog of murine MKK7gamma1. Expression of hMKK7gamma1 mRNA was assessed
      and transcripts were present in low levels in placenta, fetal liver, and skeletal
      muscle. PCR results indicate that hMKK7gamma1 is expressed in various normal
      tissues, tumors, and in synoviocytes from rheumatoid and osteoarthritis patients.
      Recombinant hMKK7gamma1 can be phosphorylated and activated by MEKK1. Further
      studies will provide insight into the role for hMKK7gamma1 versus other MKK7
      isoforms.

PMID- 16442503
TI  - Potential role of short hairpin RNA targeting epidermal growth factor receptor in
      growth and sensitivity to drugs of human lung adenocarcinoma cells.
AB  - Upregulation of expression and activation of epidermal growth factor receptor
      (EGFR) is involved in the development and progression of a wide range of human
      cancers. The present study aims at determining gene-silencing effects of vector
      based short hairpin RNA (shRNA) targeting EGFR on receptor expression and cell
      growth and evaluating its modulation of responsiveness to drugs in human lung
      adenocarcinoma cells (HLAC). A vector-based polymerase 3-promotor system was used
      to express shRNA targeting EGFR in HLAC lines (A549 and SPC-A1). EGFR was
      detected by immunofluorescence staining and quantified by Western blot. The
      effect of shRNA targeting EGFR on tumor cell growth was assessed by colony
      formation assay, cell cycle and apoptosis by flow cytometry, and the
      responsiveness of HLAC lines to cytotoxic drugs by 3-[4,5-dimethylthiozol-2yl]
      2,5-diphenyltetrazolium bromide [MTT] assay. Vectors expressing shRNA against
      EGFR significantly downregulated receptor expression by 74 and 85% and the colony
      number by 63 and 69% in A549 and SPC-A1, respectively. Vector-based shRNA against
      EGFR caused G1 arrest, induced apoptosis, and subsequently increased the
      sensitivity to cisplatin, doxorubicin and paclitaxel by about four- to seven-fold
      in both HLAC lines. Our data suggest that vector-based shRNA could be considered
      as an alternative to effectively inhibit EGFR expression in HLACs, probably with
      the higher efficacy in combination therapies with conventional chemotherapeutic
      drugs.

PMID- 16442504
TI  - Peroxisome-proliferator-activated receptor-gamma (PPARgamma) activation protects
      neurons from NMDA excitotoxicity.
AB  - A growing body of evidence indicates that the transcription factor PPARgamma
      plays a beneficial role in various neurological diseases. The postulated
      principal mechanism underlying the beneficial effects of PPARgamma is due to its
      anti-inflammatory properties. However, PPARgamma exists in neurons where it may
      provide additional effects that regulate neuronal vulnerability. In the present
      study, we employed in vitro and in vivo models of excitotoxic neuronal injury to
      test hypothesis on the neuroprotective role of PPARgamma. The endogenous
      PPARgamma ligand, 15d-Delta(12,14)-Prostaglandin J2 (15d-PGJ2), and a selective
      thiazolidinedione PPARgamma agonist, ciglitazone, significantly reduced neuronal
      death in response to glutamate and NMDA-mediated, but not kainate-mediated
      toxicity. This neuroprotective effect of 15d-PGJ2 and ciglitazone was linked to
      increased PPARgamma DNA binding activity as it was fully reversed by the
      pretreatment of neurons with selective PPARgamma antagonists and anti-PPARgamma
      antibody. It was not due to the blockade of NMDA-receptor-mediated Ca++ entry.
      Our data demonstrate that PPARgamma activation may represent a potential target
      for treatment of numerous acute and chronic neurological diseases with
      pathologies that involve excitotoxic damage.

PMID- 16442505
TI  - Iterative one-pot syntheses of chitotetroses.
AB  - Rapid syntheses of chitotetrose derivatives were achieved in good yields using
      the newly developed reactivity independent iterative one-pot strategy. The
      protective groups on donors and acceptors were independently evaluated allowing
      matching of the two partners in glycosylation. No anomeric reactivity adjustments
      or intermediate purification were necessary thus significantly improving the
      overall synthetic efficiency. Only near stoichiometric amounts of building blocks
      were required for the assembly of target molecules further highlighting the
      potential of the iterative one-pot method in complex oligosaccharide synthesis.

PMID- 16442507
TI  - Dynamics of water in supercooled aqueous solutions of glucose and poly(ethylene
      glycol)s as studied by dielectric spectroscopy.
AB  - The dielectric behaviour of aqueous solutions of glucose, poly(ethylene glycol)s
      (PEGs) 200 and 600, and poly(vinyl pyrrolidone) (PVP) has been examined at
      different concentrations in the frequency range of 10(6)-10(-3) Hz by dielectric
      spectroscopy and by using differential scanning calorimetry down to 77 K from
      room temperature. The shape of the relaxation spectra and the temperature
      dependence of the relaxation rates have been critically examined along with
      temperature dependence of dielectric strength. In addition to the so-called
      primary (alpha-) relaxation process, which is responsible for the glass
      transition event at T(g), another relaxation process of comparable magnitude has
      been found to bifurcate from the main relaxation process on the water-rich side,
      which continues to the sub-T(g) region, exhibiting relaxation at low frequencies.
      The sub-T(g) process dominates the dielectric measurements in aqueous solutions
      of higher PEGs, and the main relaxation process is seen as a weak process. The
      sub-T(g) process was not observed when water was replaced by methanol in the
      binary mixtures. These observations suggest that the sub-T(g) process in the
      aqueous mixtures is due to the reorientational motion of the 'confined' water
      molecules. The corresponding dielectric strength shows a noticeable change at
      T(g), indicating a hindered rotation of water molecules in the glassy phase. The
      nature of this confined water appears to be anomalous compared to most other
      supercooled confined liquids.

PMID- 16442506
TI  - Metal-ion interactions with sugars. Crystal structure and FT-IR study of PrCl3-D
      ribose complex.
AB  - A single-crystal of PrCl3.D-ribose.5H2O was obtained from a methanol-water
      solution and its structure determined by X-ray crystallography. Two
      configurations of the complex, as a pair of isomers, were found in the single
      crystal in a disordered state, which differs from that reported previously. The
      ligand of one of the complexes is alpha-D-ribopyranose in the 4C1 conformation,
      and the ligand of the other is beta-D-ribopyranose in the 1C4 conformation. The
      alpha:beta anomeric ratio is 54:46. Both ligands of the two isomers provide three
      hydroxyl groups in an axial-equatorial-axial orientation for coordination. The
      Pr3+ ion is nine-coordinated, with five Pr-O bonds from water molecules, three Pr
      O bonds from the hydroxyl groups of the D-ribopyranose and one Pr-Cl bond from
      chloride ion. The hydroxyl groups, water molecules, and chloride ions form an
      extensive hydrogen-bond network. The IR spectral C-C, O-H, C-O, and C-O-H
      vibrations are shifted in the complex, compared to those in d-ribose, and the IR
      results are in accord with those obtained from the X-ray diffraction study.

PMID- 16442508
TI  - Fluorinated acyclo-C-nucleoside analogues from glycals in two steps.
AB  - A convenient two-step strategy is reported for the synthesis of fluorinated
      optically pure acyclo-C-nucleoside analogues starting from simple glycals. In the
      first step, benzyl- or p-methoxybenzyl-protected glycals are treated with
      trifluoroacetic anhydride, bromodifluoroacetyl chloride, trichloroacetyl
      chloride, and perfluorooctanoyl chloride, respectively, in the presence of Et3N.
      This one-pot procedure yields 1,2-unsaturated sugars (1,5-anhydro-3,4,6-tri-O
      benzyl (or p-methoxybenzyl) 2-deoxy-2-perhalogenoacyl-D-arabino / lyxo-hex-1
      enitols 4-9) acylated at C-2. In the second step, a selective ring transformation
      is induced by treatment of the C-acylated glycals with bis-nucleophiles
      (hydrazine, phenylhydrazine, o-phenylenediamine, hydroxylamine). In particular,
      1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-trifluoroacetyl-D-arabino-hex-1-enitol
      (4) and 1,5-anhydro-2-deoxy-2-trifluoroacetyl-3,4,6-tri-O-(p-methoxybenzyl)-D
      arabino-hex-1-enitol (8) were reacted with these nucleophiles generating the
      final C-nucleoside analogues of pyrazole (10, 11, and 12), diazepine (13), and
      isoxazole (15), respectively, containing a carbohydrate side chain linked to the
      heterocyclic ring.

PMID- 16442509
TI  - Identification of polysaccharides from pericarp tissues of litchi (Litchi
      chinensis Sonn.) fruit in relation to their antioxidant activities.
AB  - A large number of polysaccharides are present in the pericarp tissues of
      harvested litchi fruits. A DEAE Sepharose fast-flow anion-exchange column and a
      Sephadex G-50 gel-permeation column were used to isolate and purify the major
      polysaccharides from litchi fruit pericarp tissues. Antioxidant activities of
      these major polysaccharide components were also evaluated. An aqueous extract of
      the polysaccharides from litchi fruit pericarp tissues was chromatographed on a
      DEAE anion-exchange column to yield two fractions. The largest amount of the
      polysaccharide fraction was subjected to further purification by gel filtration
      on Sephadex G-50. The purified product was a neutral polysaccharide, with a
      molecular weight of 14 kDa, comprised mainly of 65.6% mannose, 33.0% galactose
      and 1.4% arabinose. Analysis by Smith degradation indicated that there were 8.7%
      of (1-->2)-glycosidic linkages, 83.3% of (1-->3)-glycosidic linkages and 8.0% of
      (1-->6)-glycosidic linkages in the polysaccharide. Furthermore, different
      polysaccharide fractions extracted and purified from litchi fruit pericarp
      tissues exhibited strong antioxidant activities. Among these fractions, the
      purified polysaccharide had the highest antioxidant activity and should be
      explored as a novel potential antioxidant.

PMID- 16442510
TI  - Thrombin inhibition by antithrombin in the presence of oversulfated dermatan
      sulfates.
AB  - DSS1 and DSS2 are two oversulfated dermatan sulfate derivatives with sulfur
      contents of 7.8% and 11.5%, respectively. DSS1 and DSS2 both enhanced the rate at
      which antithrombin (AT) inactivates thrombin according to a concentration
      dependent manner. The analysis of the experimental data, using our previously
      described kinetic model [Biomaterials1997, 18, 203] (i) suggested that both DSS1
      and DSS2 catalyzed the thrombin-AT reaction according to a mechanism in which the
      oversulfated derivative quickly formed with AT a complex, which was more reactive
      towards thrombin than the free inhibitor and (ii) allowed us to determine the
      dissociation constants of the polysaccharide-inhibitor complexes, which were
      (1.15 +/- 0.74) x 10(-7) and (7.17 +/- 0.65) x 10(-9) M, and the catalyzed
      reaction rate constants, which were (2.29 +/- 0.15) x 10(8) and (8.71 +/- 0.08) x
      10(8) M(-1) min(-1), for DSS1 and DSS2, respectively. These data suggested that
      the oversulfation confers an affinity for AT to dermatan sulfate and that the
      higher the sulfur content the higher the affinity for AT. They also suggested
      that the reactivities of the polysaccharide-AT complexes formed towards the
      protease increased with the sulfur content.

PMID- 16442511
TI  - CP/MAS 13C NMR analysis of cellulase treated bleached softwood kraft pulp.
AB  - Fully bleached softwood kraft pulps were hydrolyzed with cellulase (1,4-(1,3:1,4)
      beta-D-glucan 4-glucano-hydrolase, EC 3.2.1.4) from Trichoderma reesei. Supra
      molecular structural features of cellulose during enzymatic hydrolysis were
      examined by using CP/MAS 13C NMR spectra in combination with line-fitting
      analysis. Different types of cellulose allomorphs (cellulose I(alpha), cellulose
      I(beta), para-crystalline) and amorphous regions were hydrolyzed to a different
      extent by the enzyme used. Also observed was a rapid initial phase for hydrolysis
      of regions followed by a slow hydrolysis phase. Cellulose I(alpha), para
      crystalline, and non-crystalline regions of cellulose are more susceptible to
      enzymatic hydrolysis than cellulose I(beta) during the initial phase. After the
      initial phase, all the regions are then similarly susceptible to enzymatic
      hydrolysis.

PMID- 16442512
TI  - Structural analysis of an extracellular polysaccharide produced by a benzene
      tolerant bacterium, Rhodococcus sp. 33.
AB  - Rhodococcus sp. 33 can tolerate and efficiently degrade various concentrations of
      benzene, one of the most toxic and prevailing environmental pollutants. This
      strain produces a large quantity of extracellular polysaccharide (33 EPS), which
      plays an important role in the benzene tolerance in Rhodococcus sp. 33,
      especially by helping the cells to survive an initial challenge with benzene.
      This EPS has been reported to be composed of D-galactose, D-glucose, D-mannose, D
      glucuronic acid, and pyruvic acid at a molar ratio of 1:1:1:1:1. To understand
      the protective effect of 33 EPS, we determined its chemical structure by using 1H
      and 13C NMR spectroscopy including 2D DQF-COSY, TOCSY, HMQC, HMBC, and NOESY
      experiments. The polysaccharide was shown to consist of tetrasaccharide repeating
      units with the following structure: [structure: see text].

PMID- 16442513
TI  - A computational study of structure-reactivity relationships in Na-adduct
      oligosaccharides in collision-induced dissociation reactions.
AB  - Elucidating the fragmentation mechanisms in oligosaccharides using theoretical
      calculations is useful in analyzing the experimentally obtained mass spectra.
      Semi-empirical and ab initio quantum mechanics calculations were used to study
      the relationship between the structure and reactivity and the chemical properties
      of oligosaccharides. In these calculations, sodium-cationized oligosaccharides
      were investigated to determine Na+ ion affinity at several binding positions; in
      addition, the dependence of the glycosidic bond cleavage on the Na+ position was
      examined. The calculated structures reported in this study are directed at
      interpreting experimentally observed fragment ions, resulting from the cleavage
      of the glycosidic bonds. The calculated results for oligosaccharides containing
      between three and five monosaccharide units (27 oligosaccharides) were compared
      with experimental data generated by matrix-assisted laser-desorption/ionization
      (MALDI) using a quadrupole ion trap (QIT) with a time-of-flight (TOF) mass
      spectrometer (MS).

PMID- 16442514
TI  - Complete 1H and 13C NMR assignment of digeneaside, a low-molecular-mass
      carbohydrate produced by red seaweeds.
AB  - Digeneaside (alpha-D-mannopyranosyl-(1-->2)-D-glycerate) was extracted from the
      red algae, Bostrychia binderii, and purified by adsorption and gel-filtration
      chromatography. HPLC and ESI-MS techniques were used to follow purification steps
      and characterize digeneaside. NMR spectroscopy experiments (1D 1H, 13C, DEPT and
      2D HMQC, COSY and TOCSY) were used to fully assign the 1H and 13C spectra.

PMID- 16442515
TI  - Structural elucidation of a novel fucogalactan that contains 3-O-methyl rhamnose
      isolated from the fruiting bodies of the fungus, Hericium erinaceus.
AB  - A new heteropolysaccharide, HEPF3, was isolated from the fruiting bodies of
      Hericium erinaceus. HEPF3 has a molecular weight of 1.9 x 10(4) Da and is
      composed of fucose and galactose in a ratio of 1:4.12. Compositional analysis,
      methylation analysis, together with 1H and 13C NMR spectroscopy established that
      HEPF3 consists of a branched pentasaccharide repeating unit with the following
      structure: [structure: see text]. HEPF3 also contains a minor proportion of 3-O
      methylrhamnose that is thought to terminate the polymer main chain.

PMID- 16442516
TI  - The emerging role of platelets in adaptive immunity.
AB  - Platelets' foremost role in survival is hemostasis. However, a significant
      quantity of research has demonstrated that platelets are an integral part of
      inflammation and can also be potent effector cells of the innate immune response.
      CD154, a molecule of vital importance to adaptive immune responses, is expressed
      by activated platelets and has been implicated in platelet-mediated modulation of
      innate immunity and inflammatory disease states. Recent studies in mice extend
      the role of platelet CD154 to the adaptive immune response demonstrating that
      platelets can enhance antigen presentation, improve CD8 T cell responses, and
      play a critical function in normal T-dependent humoral immunity. The latter
      studies suggest that the current paradigm for the B cell germinal center response
      should be modified to include a role for platelets.

PMID- 16442517
TI  - Feature binding in visual working memory evaluated by type identification
      paradigm.
AB  - Memory for feature binding comprises a key ingredient in coherent object
      representations. Previous studies have been equivocal about human capacity for
      objects in the visual working memory. To evaluate memory for feature binding, a
      type identification paradigm was devised and used with a multiple-object
      permanence tracking task. Using objects defined by shape and color, observers
      identified types of changes in feature combinations across an occlusion event,
      and the effects of object motion and number of switches were investigated. With
      only one switch, task performance was impaired even under stationary conditions,
      suggesting highly limited capacity of binding memory. Second switch improved
      performance only in the stationary condition, suggesting that object motion
      strongly disrupts feature binding. Further analyses and experiments suggest that
      improvement by the second switch reflects transition of binding memory by
      selective attention.

PMID- 16442518
TI  - Language-specific and universal influences in children's syntactic packaging of
      Manner and Path: a comparison of English, Japanese, and Turkish.
AB  - Different languages map semantic elements of spatial relations onto different
      lexical and syntactic units. These crosslinguistic differences raise important
      questions for language development in terms of how this variation is learned by
      children. We investigated how Turkish-, English-, and Japanese-speaking children
      (mean age 3;8) package the semantic elements of Manner and Path onto syntactic
      units when both the Manner and the Path of the moving Figure occur simultaneously
      and are salient in the event depicted. Both universal and language-specific
      patterns were evident in our data. Children used the semantic-syntactic mappings
      preferred by adult speakers of their own languages, and even expressed subtle
      syntactic differences that encode different relations between Manner and Path in
      the same way as their adult counterparts (i.e., Manner causing vs. incidental to
      Path). However, not all types of semantics-syntax mappings were easy for children
      to learn (e.g., expressing Manner and Path elements in two verbal clauses). In
      such cases, Turkish- and Japanese-speaking children frequently used syntactic
      patterns that were not typical in the target language but were similar to
      patterns used by English-speaking children, suggesting some universal influence.
      Thus, both language-specific and universal tendencies guide the development of
      complex spatial expressions.

PMID- 16442519
TI  - The roles of nitric oxide in murine cardiovascular development.
AB  - Nitric oxide (NO) participates in a diverse array of biological functions in
      mammalian organ systems. Depending on the biochemical environment, the production
      of NO may result in cytoprotection or cytotoxicity. The paradoxical actions of NO
      arise from the complexities generated by the redox milieu, NO
      concentration/bioavailability, and tissue/cell context, which ultimately result
      in the wide range of regulatory roles observed. Additionally, in physiological
      versus pathological states, NO often displays diametrically opposing affects in
      several organ systems. Here, we will discuss the roles of NO during reproduction,
      organ system development, in particular, the cardiovascular system, and its
      potential implications in diabetes-induced fetal defects.

PMID- 16442520
TI  - Validity of human nails as a biomarker of arsenic and selenium exposure: A
      review.
AB  - Human nail clippings have been used in recent epidemiological studies as a
      routine bioindicator of arsenic and selenium exposure. To ensure sound
      application of this biomarker, however, it is important to consider properties
      and scientific knowledge pertaining to validation of this particular tool. In
      this review, the use of human nails to measure exposure to arsenic and selenium
      is discussed in the context of the biomarker validation framework. Literature
      related to both analytical procedures and intrinsic characteristics of the
      biomarker is reviewed. Specifically, the followings are addressed: sample
      collection and preparation methods, establishment of the exposure-biomarker
      relationship, intraindividual variability and reproducibility of measurements,
      and biomarker-disease investigations. Drawing from a rapidly growing body of
      literature, current knowledge of these biomarker validation steps is assessed.
      Therefore, this review brings attention to the important issue of biomarker
      validation, laying the framework for future studies measuring elemental
      composition of nails.

PMID- 16442521
TI  - Behavioral and neurobiological effects of the enkephalinase inhibitor RB101
      relative to its antidepressant effects.
AB  - Nonpeptidic delta-opioid receptor agonists produce antidepressant-like effects in
      rodents, and compounds that inhibit the breakdown of endogenous opioid peptides
      have antidepressant-like effects in animal models. In this study, the behavioral
      effects of the enkephalinase inhibitor, RB101 (N-[(R, S)-2-benzyl-3-[(S)(2-amino
      4-methyl-thio)-butyldithio]-1-oxopropyl]-l-phenylalanine benzyl ester), were
      examined. Specifically, the effects of RB101 on convulsive activity, locomotor
      activity, and antidepressant-like effects in the forced swim test were studied in
      Sprague-Dawley rats, and the opioid receptor types mediating these effects were
      examined by antagonist studies. In addition, the effects of RB101 on brain
      derived neurotrophic factor (BDNF) mRNA expression were evaluated in relation to
      its antidepressant effects. RB101 produced delta-opioid receptor-mediated
      antidepressant effects (32 mg/kg i.v. and 100 mg/kg i.p.) and increased locomotor
      activity (32 mg/kg i.v.) in rats. RB101 did not produce convulsions or seizures
      and did not alter BDNF mRNA expression. In conclusion, RB101 has the potential to
      produce antidepressant effects without convulsions.

PMID- 16442522
TI  - Co-localization of cortactin and phosphotyrosine identifies active invadopodia in
      human breast cancer cells.
AB  - Invadopodia are filopodia-like projections possessing protease activity that
      participate in tumor cell invasion. We demonstrate that co-localization of
      cortactin and phosphotyrosine identifies a subset of cortactin puncta termed
      "invadopodial complexes" that we find to be closely associated with the plasma
      membrane at active sites of focal degradation of the extracellular matrix in MDA
      MB-231 breast cancer cells. Manipulation of c-Src activity in cells by
      transfection with kinase activated c-Src(527) or kinase inactive c-Src(295)
      results in a dramatic increase or decrease, respectively, in the number of these
      structures associated with changes in the number of sites of active matrix
      degradation. Overexpression of kinase-inactive c-Src(295) does not prevent
      localization of cortactin at the membrane; however, co-localized phosphotyrosine
      staining is decreased. Thus, elevated phosphotyrosine at invadopodial complexes
      is specifically associated with the proteolytic activity of invadopodia. Further,
      invadopodial complexes are spatially, morphologically and compositionally
      distinct from focal adhesions as determined by localization of focal adhesion
      kinase (FAK), which is not present in invadopodial complexes. Expression of
      kinase-inactive c-Src(295) blocks invadopodia activity, but does not block
      filopodia formation. Thus, invadopodia, but not filopodia, are highly correlated
      with matrix invasion, and sites of invadopodial activity can be identified by the
      formation of invadopodial complexes.

PMID- 16442523
TI  - Caldesmon transgene expression disrupts focal adhesions in HTM cells and
      increases outflow facility in organ-cultured human and monkey anterior segments.
AB  - Cytoskeleton modulating compounds have been shown to lower intraocular pressure
      (IOP) and increase outflow facility. Caldesmon is one protein that is involved in
      the regulation of actin stress fiber formation. The effects of rat non-muscle
      caldesmon (Cald) gene over-expression on focal adhesions in human trabecular
      meshwork (HTM) cells and on outflow facility in organ-cultured human and monkey
      anterior segments were determined. Treatment of HTM cells with adenovirus
      delivered caldesmon (AdCaldGFP) resulted in characteristic changes in the actin
      cytoskeleton and matrix adhesions within 24-48 hr post-transduction. Stress
      fibers gradually disappeared and novel actin structures were formed (see
      manuscript by Grosheva et al., this issue). In cells with disrupted stress
      fibers, vinculin-containing focal adhesions were also disrupted. In organ
      cultured anterior segments, baseline outflow facility (microl min-1 mmHg-1) for
      all anterior segments averaged (mean+/-sem): human, 0.19+/-0.03 (n=12); monkey,
      0.36+/-0.02 (n=19). In human anterior segments, transduction with 10(7) plaque
      forming units of AdGFPCald increased outflow facility by 43+/-21% (p<or=0.11,
      n=6) at 66 hr compared to baseline and corrected for the changes in outflow
      facility of the contralateral vehicle treated segment. Using the same time point,
      i.e. 2-3 days after injection, outflow facility in monkey anterior segments,
      transduced with 1.5x10(7) plaque forming units of AdGFPCald was increased by 35+/
      18%, p<0.2, n=10 compared to baseline and corrected for the change in outflow
      facility in the contralateral AdGFP treated segment. Combining human (66 hr) and
      monkey (2-3 days) data, outflow facility was increased by 38+/-13%, p<0.02, n=16.
      Additional analysis of maximum responses in monkey anterior segments from 1 to 6
      days after transduction showed outflow facility was increased by 66+/-18%,
      p<0.01, n=10. Caldesmon over-expression, which relaxes cultured HTM cells and
      disrupts their actin cytoskeleton and cell-matrix adhesions, also appears to
      increase outflow facility in organ-cultured human and monkey anterior segments.
      This suggests that over-expression of the caldesmon gene in the TM may be an
      effective approach for the gene therapy of glaucoma.

PMID- 16442524
TI  - Transgenic studies on the role of optineurin in the mouse eye.
AB  - Mutations in the OPTN gene encoding for optineurin have been associated with
      primary open-angle glaucoma. The functional role(s) of optineurin in the normal
      and glaucomatous eye are unclear. As optineurin interferes with TNF-alpha
      mediated cell death in vitro, an involvement of optineurin in the regulatory
      pathways leading to apoptosis of retinal ganglion cells has been suggested. The
      goal of the present study was to study the molecular properties of optineurin and
      its capabilities to prevent apoptosis in vivo in the eyes of transgenic mice. The
      chicken betaB1-crystallin promoter was used to overexpress ectopic optineurin in
      the lenses of transgenic mice. The expression of transgenic mRNA was monitored by
      northern blot analysis. The localization of transgenic optineurin was
      investigated by one- and two-dimensional western blot analysis and by
      immunohistochemistry, and compared with that of endogenous optineurin. To assess
      effects of transgenic optineurin on apoptosis, betaB1-crystallin-OPTN mice were
      crossbred with betaB1-crystallin-TGFbeta1 mice that undergo substantial TGF-beta1
      induced apoptotic cell death in the lens. Two independent betaB1-crystallin-OPTN
      transgenic lines were established, in which transgenic optineurin was expressed
      strictly lens-specific as assessed by Northern and Western blotting, and by
      immunohistochemistry. In contrast, endogenous optineurin was preferentially
      expressed in the retina, where retinal ganglion cells showed strong labeling.
      Immunostaining for endogenous optineurin in the anterior eye was considerably
      weaker than in the posterior eye and was seen in iris, ciliary epithelium, cells
      of corneal stroma and endothelium, and in the trabecular meshwork. Neither
      transgenic nor endogenous optineurin was found in the aqueous humor. Transgenic
      overexpression of optineurin did not have measurable effects on TGFbeta1-induced
      apoptosis in mixed betaB1-crystallin-OPTN/betaB1-crystallin-TGFbeta1 transgenic
      mice. Our results show that optineurin is a cytoplasmatic rather than a secretory
      protein that is preferentially expressed in retinal ganglion cells, and argue
      against a major role of optineurin for the modulation of apoptosis in vivo.

PMID- 16442525
TI  - Monkey organ-cultured anterior segments: technique and response to H-7.
AB  - In the intact primate eye in vivo, it may be difficult to determine whether an
      outflow facility response is due to direct effects on the trabecular meshwork or
      indirectly via an effect on ciliary muscle tone unless complicated surgical
      ciliary muscle disinsertion or isotope accumulation procedures are used. We
      established a monkey anterior segment organ culture system modeled after the
      human anterior segment organ culture system and determined its characteristics
      and response to H-7, an agent shown to increase trabecular outflow in vivo and in
      other organ culture systems. Outflow facility studies conducted using the monkey
      organ-cultured anterior segment system showed that: baseline values were
      comparable to those measured in vivo; washout occurred with time; the two-level
      constant pressure perfusion technique gave results comparable to the constant
      rate technique; species differences were found comparing baseline outflow
      facility and intraocular pressure in rhesus and cynomolgus monkey organ-cultured
      anterior segments; there was no effect of age on outflow facility in either
      species by one-way ANOVA; anterior segment exchange perfusion increased outflow
      facility if measured within 1 hr of the exchange; the magnitude of the response
      to H-7 was comparable to those reported in vivo and in other in vitro systems.
      The onset of the response to H-7 was delayed in most cases (day after H-7
      exchange), compared to in vivo monkey studies (onset 6-9 min) and in vitro human
      and porcine organ culture systems (within 1 hr). Also the duration of the
      response (2-3 days from the onset) was longer than that found for in vitro human
      studies (1 day). Thus, the monkey organ-cultured anterior segment system can be
      used to determine the effects of pharmacological and biological agents on
      trabecular outflow.

PMID- 16442526
TI  - In vitro and in vivo differentiation of boundary cap neural crest stem cells into
      mature Schwann cells.
AB  - Boundary cap cells can generate neurons as well as peripheral glia during
      embryonic development (Maro, G.S., Vermeren, M., Voiculescu, O., Melton, L.,
      Cohen, J., Charnay, P., Topilko, P., 2004. Neural crest boundary cap cells
      constitute a source of neuronal and glial cells of the PNS. Nat Neurosci. 7 (9),
      930-938), and, recently, the boundary cap was shown to contain multipotent stem
      cells (Hjerling-Leffler, J., Marmigere, F., Heglind, M., Cederberg, A.,
      Koltzenburg, M., Enerback, S., Ernfors, P., 2005. The boundary cap, a source of
      neural crest stem cells generating multiple sensory neuron subtypes. Development.
      132 (11), 2623-2632). The ability of stem cells to generate mature functional
      glial phenotypes has not been addressed. In this study, we have explored the
      competence of boundary neural crest stem cells (bNCSCs) to differentiate into
      mature functional Schwann cells (SCs) in vitro and in vivo. bNCSCs failed to
      differentiate into SCs in vitro when cultured in a defined media and in vivo when
      grafted into adult rat sciatic nerves. However, in the presence of neuregulins,
      during long-term cultures, the majority of bNCSCs differentiated into SCs. After
      analysis of the in vivo expression of Sox2, Sox10, S100, GFAP, fibronectin and
      Krox20 in the glial lineages, we used these markers to characterize
      differentiation of the bNCSCs. Gliogenesis of bNCSCs proceeded similar to that in
      vivo by sequentially adopting a SC precursor and immature Schwann cell before
      maturing into myelinating and non-myelinating SCs. In co-culture with explanted
      dorsal root ganglia (DRG) as well as in vivo in transplants to the axotomized
      sciatic nerve, these bNCSC-derived SCs myelinated axons as shown by ensheathing
      of neuronal processes and expression of myelin basic proteins (MBP). These
      results show that, under appropriate conditions, bNCSCs can generate mature SCs
      that are functional and can myelinate axons in regenerating nerves.

PMID- 16442527
TI  - Functional impacts of non-synonymous single nucleotide polymorphisms: selective
      constraint and structural environments.
AB  - In this work, we studied the correlations between selective constraint,
      structural environments and functional impacts of non-synonymous single
      nucleotide polymorphisms (nsSNPs). We found that the relation between solvent
      accessibility and functional impacts of nsSNPs is not as simple as generally
      thought. Finer structural classifications need to be taken into account to reveal
      the complex relations between the characteristics of a structure environment and
      its influence on the functional impacts of nsSNPs. We introduced two parameters
      for each structural environment, consensus residue percentage and residue
      distribution distance, to characterize the selective constraint imposed by the
      environment. Both parameters significantly correlate with the functional bias of
      nsSNPs across the structural environments. This result shows that selective
      constraint underlies the bias of a structural environment towards a certain type
      of nsSNPs (disease-associated or benign).

PMID- 16442528
TI  - Roles of ethylene receptor NTHK1 domains in plant growth, stress response and
      protein phosphorylation.
AB  - Ethylene receptors sense ethylene and regulate downstream signaling events.
      Tobacco ethylene receptor NTHK1, possessing Ser/Thr kinase activity, has been
      found to function in plant growth and salt-stress responses. NTHK1 contains
      transmembrane domains, a GAF domain, a kinase domain and a receiver domain. We
      examined roles of these domains in regulation of plant leaf growth, salt-stress
      responses and salt-responsive gene expressions using an overexpression approach.
      We found that the transgenic Arabidopsis plants harboring the transmembrane
      domain plus kinase domain exhibited large rosettes, had reduction in ethylene
      sensitivity, and showed enhanced salt sensitivity. The transgenic plants
      harboring the transmembrane domain plus GAF domain also showed larger rosettes.
      Truncations of NTHK1 affected salt-induced gene expressions. Transmembrane domain
      plus kinase domain promoted RD21A and VSP2 expression but decreased salt
      induction of AtNAC2. The kinase domain itself promoted AtERF4 gene expression.
      The GAF domain itself enhanced Cor6.6 induction. Moreover, the NTHK1 functional
      kinase domain phosphorylated the HIS and ATP subdomains, and five putative
      phosphorylation sites were identified in these two subdomains. In addition, the
      salt-responsive element of the NTHK1 gene was in the transmembrane-coding region
      but not in the promoter region. These results indicate that NTHK1 domains or
      combination of them have specific functions in plant leaf growth, salt-stress
      response, gene expression and protein phosphorylation.

PMID- 16442529
TI  - Bcr interferes with beta-catenin-Tcf1 interaction.
AB  - The beta-catenin/Tcf complex is a downstream effector of the Wnt signalling
      pathway. It is a transcription complex, which activates gene expression and
      contributes to proliferation and tumor progression. Tcf1 in complex with beta
      catenin is able to activate beta-catenin-dependent gene expression. We
      demonstrate that expressed Bcr is able to bind the transcription factor Tcf1 to
      disrupt the Tcf1/beta-catenin complex. Phosphorylation of Bcr by the tyrosine
      kinase pp60(src) can lead to dissociation of the transcriptionally inactive
      Bcr/Tcf1 complex. Thus two independent mechanisms may regulate Tcf/beta-catenin
      mediated transcription via Bcr: binding to beta-catenin as we have previously
      shown and to Tcf1 as shown here.

PMID- 16442530
TI  - Proteome analysis of rat liver mitochondria reveals a possible compensatory
      response to endotoxic shock.
AB  - Organ failure induced by endotoxic shock has recently been associated with
      affected mitochondrial function. In this study, effects of in vivo
      lipopolysaccharide-challenge on protein patterns of rat liver mitochondria in
      treated animals versus controls were studied by two-dimensional electrophoresis
      (differential image gel electrophoresis). Significant upregulation was found for
      ATP-synthase alpha chain and superoxide dismutase [Mn]. Our data suggest that
      endotoxic shock mediated changes in the mitochondrial proteome contribute to a
      compensatory reaction (adaptation to endotoxic shock) rather than to a mechanism
      of cell damage.

PMID- 16442531
TI  - Repression of SOX6 transcriptional activity by SUMO modification.
AB  - SOX6 plays key functions in several developmental processes, including
      neurogenesis and skeleton formation. In this report, we show that SOX6 is
      modified in vitro and in vivo by small ubiquitin-related modifier (SUMO) on two
      distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased
      SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription
      was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a
      SUMO protease increased SOX6 transcriptional activity. Furthermore, co-expression
      of SOX6 with SUMO2 results in the appearance of SOX6 in a punctate nuclear
      pattern that colocalized with promyelocytic leukemia protein, which was partially
      abolished by mutations in SOX6 sumoylation sites.

PMID- 16442532
TI  - Interaction of metallothionein with tumor suppressor p53 protein.
AB  - Previous reports have shown that metallothionein (MT) may modulate p53 activity
      through zinc exchange. However, little is known on a direct interaction between
      MT and p53 in cells. The results demonstrate an interaction between MT and p53
      can occur in vitro. The complex between MT and p53 was observed in breast cancer
      epithelial cells with both wild and inactive type of p53. Furthermore, it was
      shown that wt-p53 was preferentially associated with Apo-MT. Our data suggest
      that co-expression of MT and p53 and their complex formation in tumor cells may
      be involved in regulation of apoptosis in these cells.

PMID- 16442533
TI  - Cloning, expression, and biological activity of growth hormone in bullfrog (Rana
      catesbeiana).
AB  - The cDNA (GenBank, AY251538) encoding bullfrog growth hormone (fGH) was cloned by
      RT-PCR from the total RNA of pituitary glands. Its sequence encoded a putative
      polypeptide of 215 amino acids, including a signal peptide of 25 amino acids with
      no change to those of other previous reported bullfrog GHs. The fGH precursor
      shares 98.1, 96.3, and 95.3% homologies to those of other bullfrog GHs (AAB24792,
      AAB19428, CAA31038) in amino-acid sequence and its nucleotide sequences of the
      coding region shares 99.1 and 98.5% homologies to those of previous bullfrog GH
      genes (S52027 and X12520). The fGH cDNA was also efficiently expressed in
      Escherichia coli carrying a plasmid pGfGH in which the cDNA was under the control
      of GST promoter of pGEX1-lambdaT. The expressed fusion protein GST-fGH is
      comprised about 29.3% of the total cellular protein in such bacteria. The
      purified GST-fGH cannot only showed a obvious dose-response curve when it reacted
      with the hepatic membrane receptor proteins from bullfrog, but also significantly
      increased the body weight and length of bullfrog after twice injection and such
      effects lasted two or three weeks after the last injection with purified GST-fGH.

PMID- 16442534
TI  - Species and individual differences in juvenile female alloparental care are
      associated with oxytocin receptor density in the striatum and the lateral septum.
AB  - The neuropeptide oxytocin has been implicated in the regulation of affiliative
      behavior and maternal responsiveness in several mammalian species. Rodent species
      vary considerably in the expression of juvenile alloparental behavior. For
      example, alloparental behavior is spontaneous in juvenile female prairie voles
      (approximately 20 days of age), takes 1-3 days of pup exposure to develop in
      juvenile rats, and is nearly absent in juvenile mice and meadow voles. Here, we
      tested the hypothesis that species differences in pup responsiveness in juvenile
      rodents are associated with oxytocin receptor (OTR) density in specific brain
      regions. We found that OTR density in the nucleus accumbens (NA) is highest in
      juvenile prairie voles, intermediate in juvenile rats, and lowest in juvenile
      mice and meadow voles. In the caudate putamen (CP), OTR binding was highest in
      prairie voles, intermediate in rats and meadow voles, and lowest in mice. In
      contrast, the lateral septum (LS) shows an opposite pattern, with OTR binding
      being high in mice and meadow voles and low in prairie voles and rats. Thus,
      alloparental responsiveness in juvenile rodents is positively correlated with OTR
      density in the NA and CP and negatively correlated with OTR density in the LS. We
      then investigated whether a similar receptor-behavior relationship exists among
      juvenile female prairie voles by correlating individual variation in alloparental
      behavior with variation in OTR density. The time spent adopting crouching
      postures, the most distinctive component of alloparental behavior in juveniles,
      was positively correlated with OTR density in the NA (r = 0.47) and CP (r = 0.45)
      and negatively correlated with OTR density in the lateral septum (r = -0.53).
      Thus, variation in OTR density in the NA, CP, and LS may underlie both species
      and individual differences in alloparental care in rodents.

PMID- 16442535
TI  - Fetal gallstones detected by routine third trimester ultrasound.

PMID- 16442536
TI  - Making EmOC a reality--CARE's experiences in areas of high maternal mortality in
      Africa.
AB  - OBJECTIVE: This paper describes the package of interventions undertaken by the
      CARE/AMDD program collaboration to increase the availability and quality of
      emergency obstetric care for 3 high maternal mortality countries in Africa.
      METHODS: Project implementation over 4 years focused on enhancing the capacity of
      10 district hospitals in 3 countries - Tanzania, Rwanda and Ethiopia.
      Interventions were designed to create functional health facilities with trained
      and competent staff, working in an enabling environment supporting EmOC service
      delivery. RESULTS: By keeping a clear focus on EmOC, the project achieved modest
      improvements in services, even in the face of the considerable constraints of
      rural district hospitals. Availability and utilization of EmOC increased in
      Tanzania; the met need for EmOC increased slightly from 14% in year 1 to 19% in
      year 4, while in Rwanda it increased from 16% to 25% over 4 years. Case fatality
      rates (CFR) declined by 30-50% in all 3 countries. While still well below UN
      recommendations, in all 3 countries there was also a progressive increase in the
      cesarean section rates, a life saving obstetric intervention. CONCLUSIONS: The
      increases in met need and decreases in case fatality suggest that project
      interventions improved the quality and use of EmOC, a critical component for
      saving women's lives.

PMID- 16442537
TI  - Comparison of microsatellite and antigen-coding loci for differentiating
      recrudescing Plasmodium falciparum infections from reinfections in Kenya.
AB  - We have compared the ability of five Plasmodium falciparum microsatellites and
      three antigen-coding loci to differentiate recrudescence from reinfection. We
      used 133 pairs of P. falciparum-infected blood samples collected during in vivo
      drug efficacy trials from three sites in Kenya with different malaria
      endemicities. There were no significant differences between the marker subsets in
      their ability to discriminate recrudescences from new infections across the three
      sites. Overall, microsatellite loci revealed significantly higher expected
      heterozygosity and multiplicity of infection levels than antigen-coding loci. The
      mean expected heterozygosity across all loci in the three populations was
      significantly higher with microsatellites (0.70, 0.78 and 0.79) than antigen
      coding loci (0.53, 0.60 and 0.62) for Mwea, Tiwi and Bondo areas, respectively.
      These observations can be explained by three non-exclusive hypotheses: (i)
      microsatellites are more polymorphic than antigenic loci; (ii) partially immune
      hosts remove certain parasites from infections on the basis of their antigenic
      alleles; and/or (iii) recombination occurs in vitro or in vivo with
      microsatellites.

PMID- 16442539
TI  - Transmission and burden and the impact of temperature on two species of
      vertically transmitted microsporidia.
AB  - Microsporidia are unusual amongst eukaryotic parasites in that they utilize both
      vertical and horizontal transmission and vertically transmitted species can cause
      sex ratio distortion in their host. Here we study vertical transmission in two
      species of feminising microsporidia, Nosema granulosis and Dictyocoela duebenum,
      infecting a single population of the crustacean host Gammarus duebeni and measure
      the effect of temperature on parasite transmission and replication. N. granulosis
      was vertically transmitted to 82% of the host embryos and D. duebenum was
      transmitted to 72% of host embryos. For both parasites, we report relatively low
      parasite burdens in developing host embryos. However, the parasites differ in
      their pattern of replication and burden within developing embryos. Whilst N.
      granulosis undergoes replication during host development, the burden of D.
      duebenum declines, leading us to propose that parasite dosage and feminisation
      efficiency underlie the different parasite frequencies in the field. We also
      examine the effect of temperature on parasite transmission and replication.
      Temperature does not affect the percentage of young that inherit the infection.
      However, low temperatures inhibit parasite replication relative to host cell
      division, resulting in a reduction in parasite burden in infected embryos. The
      reduced parasite burden at low temperatures may underpin reduced feminization at
      low temperatures and so limit the spread of sex ratio distorters through the host
      population.

PMID- 16442538
TI  - The fork head transcription factor FKTF-1b from Strongyloides stercoralis
      restores DAF-16 developmental function to mutant Caenorhabditis elegans.
AB  - The purpose of this study was to determine whether Strongyloides stercoralis FKTF
      1, a transcription factor of the FOXO/FKH family and the likely output of
      insulin/IGF signal transduction in that parasite, has the same or similar
      developmental regulatory capabilities as DAF-16, its structural ortholog in
      Caenorhabditis elegans. To this end, both splice variants of the fktf-1 message
      were expressed under the control of the daf-16alpha promoter in C. elegans
      carrying loss of function mutations in both daf-2 (the insulin/IGF receptor
      kinase) and daf-16. Under well-fed culture conditions the majority (91%) of
      untransformed daf-2; daf-16 double mutants developed via the continuous
      reproductive cycle, whereas under the same conditions 100% of daf-2 single
      mutants formed dauers. Transgenic daf-2; daf-16 individuals expressing fktf-1b
      showed a reversal of the double mutant phenotype with 75% of the population
      forming dauers under well-fed conditions. This phenotype was even more pronounced
      than that of daf-2; daf-16 mutants transformed with a homologous rescuing
      construct, daf-16alpha::daf-16a (56% dauers under well fed conditions),
      indicating that S. stercoralis fktf-1b can almost fully rescue loss-of-function
      mutants in C. elegans daf-16. By contrast, daf-2; daf-16 mutants expressing S.
      stercoralis fktf-1a, encoding the second splice variant of FKTF-1, showed a
      predominantly continuous pattern of development identical to that of the parental
      double mutant stock. This indicates that, unlike FKTF-1b, the S. stercoralis
      transcription factor FKTF-1a cannot trigger the shift to dauer-specific gene
      expression in C. elegans.

PMID- 16442540
TI  - Actions of glutamate and ivermectin on the pharyngeal muscle of Ascaridia galli:
      a comparative study with Caenorhabditis elegans.
AB  - The actions of glutamate and ivermectin were examined in the pharynx of Ascaridia
      galli and the results compared with those on the pharynx of Caenorhabditis
      elegans. In both preparations glutamate elicits a depolarization and inhibition
      of pharyngeal pumping, but the response of the pharynx of A. galli was much less
      than for C. elegans. This may be either because the pharyngeal membrane potential
      of the former is closely linked to the equilibrium potential for chloride ions
      (E(Cl)) while that of C. elegans is independent of E(Cl), or that there is a
      lower density of glutamate receptors on the pharyngeal muscle of A. galli
      compared with C. elegans. The maximum depolarization to glutamate of the
      pharyngeal muscle was 4.5+/-0.8 mV in A. galli while it was >25 mV in C. elegans.
      Picrotoxin was a weak antagonist of the glutamate response in both species.
      Flufenamic acid, pentobarbitone and flurazepam had no significant effect on
      either preparation at concentrations up to 100 microM. Three glutamate receptor
      agonists, ibotenate, kainate and quisqualate were all more potent than glutamate
      on the A. galli pharyngeal muscle. In contrast, only ibotenate was more potent
      than glutamate in C. elegans pharynx, the other two agonists being approximately
      20 times less potent. The potency of ivermectin differed markedly between the two
      species, being approximately three orders of magnitude less potent on the pharynx
      of A. galli compared with C. elegans. This study demonstrates clear differences
      between the properties of the pharyngeal muscle of the two species and shows that
      care must be taken when extrapolating data from free-living to parasitic species
      of nematode.

PMID- 16442541
TI  - Infection of naive, free-living brushtail possums (Trichosurus vulpecula) with
      the nematode parasite Parastrongyloides trichosuri and its subsequent spread.
AB  - Despite the importance of spatial processes in host-parasite interactions,
      parasite dispersal has been the subject of few experimental studies. Introduced
      marsupial common brushtail possums (Trichosurus vulpecula) are a major
      environmental and agricultural pest in New Zealand. Parastrongyloides trichosuri,
      an intestinal rhabdiasoid nematode parasite specific to possums, is being
      evaluated as a self-disseminating delivery system for engineered fertility
      control vaccines. This study addressed whether an artificial infection could be
      established in a naive, free-living possum population, by measuring the post
      release dynamics of possum-parasite interactions at the release site, and by
      following the spread of the parasite into surrounding possum populations.
      Infection was established efficiently by applying infective larvae to the skin of
      possums on a single occasion. All experimentally infected possums recaptured 3
      weeks after infection had parasite eggs in their faeces. Over the subsequent 2.5
      years, infection spread steadily over an area of about 6000 ha. Infection
      persisted at the original release site for the 3.5 years of the study and at a
      nearby site infected by natural spread for more than 3 years. Seasonal changes in
      faecal egg counts were similar at the two sites. The rapid establishment of the
      parasite and its spread provide additional support for its ongoing development as
      a vaccine delivery system.

PMID- 16442542
TI  - The complete mitochondrial genome of Anisakis simplex (Ascaridida: Nematoda) and
      phylogenetic implications.
AB  - We determined the nucleotide sequence of the complete mitochondrial genome of the
      nematode species Anisakis simplex. The genome is circular, 13,916 bp in size and
      conforms to the general characteristics of nematode mitochondrial DNAs. The gene
      arrangement of A. simplex is the same as that of Ascaris suum and almost
      identical to those of rhabditid species with a minor exception concerning the
      relative position of the AT-rich and non-coding regions and radically different
      from those of spirurid species. Along with comparisons of gene arrangement,
      phylogenetic analyses (maximum parsimony, neighbour joining and maximum
      likelihood methods) based on concatenated amino acid sequences of 12 protein
      coding genes from 13 nematode species provided strong support for the sister
      group relationship between Ascaridida and Rhabditida. The Shimodaira-Hasegawa and
      Templeton's tests both rejected the alternative hypothesis of a closer
      relationship between Ascaridida and Spirurida. These results contradicted the
      traditional view of nematode classification and a recent molecular phylogenetic
      study of 18S rDNA data that assigned Ascaridida and Spirurida as being a sister
      group. Mapping of gene arrangement across the phylogenetic tree lead to the
      assumption that the conserved gene arrangement found in Ascaridida-Rhabditida
      members might have been acquired after the most recent common ancestor of
      ascaridid/rhabditid members branched off from the basal stock of the rhabditid
      lineage.

PMID- 16442543
TI  - A COOH-terminal domain regulates the activity of Leishmania proton pumps LDH1A
      and LDH1B.
AB  - Leishmania donovani requires actively transporting proton efflux pumps to survive
      the acidic environment of macrophage phagolysosomal vacuoles and to maintain an
      electrogenic H(+) gradient for nutrient uptake. The L. donovani genome contains a
      differentially expressed pair of genes, LDH1A and LDH1B, with homology to yeast
      H(+)-ATPases that are 98% identical in sequence with amino acid differences
      concentrated at the COOH-terminus (15 of last 37 differ), a region implicated in
      regulation of yeast and plant proton pumps. Functional complementation of a
      Saccharomyces cerevisiae strain deficient in endogenous H(+)-ATPase activity,
      support of yeast growth at low pH, and ability to acidify media demonstrate that
      LDH1A and LDH1B encode proton pumps. LDH1A and LDH1B encode a COOH-terminal
      autoinhibitory domain as COOH-truncated peptides support increased rates of
      growth in yeast, enhanced media acidification, increased enzyme activity (V(max))
      and decreased K(m). This regulatory domain mediates differing function
      properties; LDH1A, but not LDH1B, supports yeast growth at pH 3 and LDH1A shows a
      greater ability to acidify media. Deletion of the last eight amino acids from
      LDH1B permits growth at pH 3 and increases media acidification, swapping of the
      COOH-tails between LDH1A and LDH1B results in LDH1A (with LDH1B tail) unable to
      support yeast growth at pH 3 and LDH1B (with LDH1A tail) now able to support
      growth at pH 3. Replacement of the COOH-terminal eight amino acids of LDH1B with
      those from LDH1A also confers the ability to support growth at pH 3. The
      complementation system for the Leishmania proton pumps in yeast described here
      provides a means to dissect the functional properties of the two isoforms, a
      convenient supply of protein for structural analysis and a model amenable to
      screening proton pump inhibitors for potential anti-leishmanial therapeutics.

PMID- 16442544
TI  - Plasmodium falciparum infection and exoerythrocytic development in mice with
      chimeric human livers.
AB  - The exoerythrocytic stage of Plasmodium falciparum has remained a difficult phase
      of the parasite life-cycle to study. The host and tissue specificity of the
      parasite requires the experimental infection of humans or non-human primates and
      subsequent surgical recovery of parasite-infected liver tissue to analyze this
      stage of the parasites development. This type of study is impossible in humans
      due to obvious ethical considerations and the cost and complexity in working with
      primate models has precluded their use for extensive studies of the
      exoerythrocytic stage. In this study we assessed, for the first time, the use of
      transgenic, chimeric mice containing functioning human hepatocytes as an
      alternative for modeling the in vivo interaction of P. falciparum parasites and
      human hepatocytes. Infection of these mice with P. falciparum sporozoites
      produced morphologically and antigenically mature liver stage schizonts
      containing merozoites capable of invading human red blood cells. Additionally,
      using microdissection, highly enriched P. falciparum liver stage parasites
      essentially free of hepatocyte contamination, were recovered for molecular
      studies. Our results establish a stable murine model for P. falciparum that will
      have a wide utility for assessing the biology of the parasite, potential anti
      malarial chemotherapeutic agents and vaccine design.

PMID- 16442545
TI  - Serum lipid concentration in relation to anthropometric indices of central and
      peripheral fat distribution in 20,021 British men and women: results from the
      EPIC-Norfolk population-based cohort study.
AB  - AIMS: Central adiposity has been linked with adverse metabolic profile including
      dyslipidaemia but recent studies suggested that peripheral fat distribution play
      a role in regulating daily fluxes in circulating non-esterified fatty acids. We
      examine whether lipid levels vary between central and peripheral fat distribution
      in the general population. METHODS AND RESULTS: We examined the cross-sectional
      relation between fat distribution indices and lipid concentration in 20,021
      apparently healthy men and women of the Norfolk cohort of the European
      Investigation into Cancer and Nutrition (EPIC-Norfolk). Waist-hip ratio was
      positively related to total and low density lipoprotein (LDL) cholesterol and
      negatively related to high density lipoprotein (HDL) cholesterol in both men and
      women, independently of body mass index (BMI). Although similar results were
      noted for waist circumference, individuals with bigger hip circumference had
      lower total and LDL-cholesterol and higher HDL-cholesterol when adjusting for BMI
      and/or waist circumference in both men and women. CONCLUSION: Regional fat
      distribution was related to lipid profile independently of BMI. The independent
      contribution of waist and hip circumference in opposite directions was
      intriguing. These findings may help explain the associations observed between
      different fat distribution phenotypes and coronary heart disease.

PMID- 16442546
TI  - Epidemiological evidence for an association between habitual tea consumption and
      markers of chronic inflammation.
AB  - BACKGROUND: Tea consumption has been inversely related to the risk of
      cardiovascular disease, but the mechanism behind this cardioprotective role is
      not fully understood. In vitro and animal model studies suggest an anti-oxidative
      and/or anti-inflammatory role. We aimed at investigating the association between
      tea drinking and indicators of low-grade inflammation in humans. METHODS: We used
      observational data from 1031 healthy men participating in a larger cross
      sectional study (BELSTRESS). Tea consumption was determined according to a semi
      quantitative food frequency questionnaire. Blood samples were analysed for C
      reactive protein (CRP), serum amyloid A (SAA), serum haptoglobin and plasma
      fibrinogen. RESULTS: Of all participants, 22% consumed tea regularly while 10%
      drank more than two cups per day. Tea drinkers were less obese, smoked less and
      drank less alcohol and coffee. CRP, SAA and haptoglobin were significantly
      associated with tea consumption, the effect being graded for SAA. Multivariate
      analysis did confirm the independence of the observed beneficial role of tea
      drinking. Fibrinogen levels were however not different between habitual tea
      consumers and non-consumers. Coffee drinking proved unrelated to chronic
      inflammation. CONCLUSION: Tea drinking might be of interest in reducing the
      inflammatory process underlying cardiovascular disease. In light of the fact that
      tea is the most consumed beverage in the world after water, our findings might be
      of importance from a public health perspective.

PMID- 16442547
TI  - Differences in lower limb transverse plane joint moments during gait when
      expressed in two alternative reference frames.
AB  - When comparing previous studies that have measured the three-dimensional moments
      acting about the lower limb joints (either external moments or opposing internal
      joint moments) during able-bodied adult gait, significant variation is apparent
      in the profiles of the reported transverse plane moments. This variation cannot
      be explained on the basis of adopted convention (i.e. external versus internal
      joint moment) or inherent variability in gait strategies. The aim of the current
      study was to determine whether in fact the frame in which moments are expressed
      has a dominant effect upon transverse plane moments and thus provides a valid
      explanation for the observed inconsistency in the literature. Kinematic and
      ground reaction force data were acquired from nine able-bodied adult subjects
      walking at a self-selected speed. Three-dimensional hip, knee and ankle joint
      moments during gait were calculated using a standard inverse dynamics approach.
      In addition to calculating internal joint moments, the components of the external
      moment occurring in the transverse plane at each of the lower limb joints were
      calculated to determine their independent effects. All moments were expressed in
      both the laboratory frame (LF) as well as the anatomical frame (AF) of the distal
      segment. With the exception of the ankle rotation moment in the foot AF, lower
      limb transverse plane joint moments during gait were found to display
      characteristic profiles that were consistent across subjects. Furthermore, lower
      limb transverse plane joint moments during gait differed when expressed in the
      distal segment AF compared to the LF. At the hip, the two alternative reference
      frames produced near reciprocal joint moment profiles. The components of the
      external moment revealed that the external ground reaction force moment was
      primarily responsible for this result. Lower limb transverse plane joint moments
      during gait were therefore found to be highly sensitive to a change in reference
      frame. These findings indicate that the different transverse plane joint moment
      profiles during able-bodied adult gait reported in the literature are likely to
      be explained on this basis.

PMID- 16442548
TI  - Pore size characterization of monolith for electrochromatography via atomic force
      microscopy studies in air and liquid phase.
AB  - This paper investigates the use of scanning electron microscopy (SEM) and atomic
      force microscopy (AFM) for the characterization of monoliths used in capillary
      electrochromatography (CEC) while focusing on the nature of the information
      available from both techniques. SEM imaging revealed a compact structure of non
      porous micrometer sized particles homogeneously agglomerated. With a simple AFM
      methodology, we found by direct observation that the same material exhibits
      mesopores in the nanometer range while SEM showed non-porous surfaces. These
      results obtained by AFM clearly showed that micrometer sized particles shrank and
      micrometer sized pores increased in the monolith when wetted. Thus, AFM was
      capable of demonstrating the morphological differences between wet and dried
      monolithic materials that are not possible by other imaging methods at micrometer
      resolution.

PMID- 16442549
TI  - Gas chromatographic-tandem mass spectrometric method for the quantitation of
      carbofuran, carbaryl and their main metabolites in applicators' urine.
AB  - A new gas chromatographic-tandem mass spectrometric method has been developed and
      validated for the determination of two N-methylcarbamates, carbofuran and
      carbaryl and their metabolites in applicators' urine specimens. Mild conditions
      were used for sample preparation based on enzymic hydrolysis and solid-phase
      extraction using Oasis HLB sorbent cartridges. Amides, phenols and ketones were
      first converted to volatile derivatives of trifluoroacetic acid anhydride (TFAA)
      and afterwards were quantitated using tandem mass spectrometry. Linear
      calibration equations (1-200 ng mL(-1) urine) were obtained from fortified urine
      samples for all eight compounds, carbaryl, 1-naphthol, 2-naphthol, and
      carbofuran, 3-hydroxycarbofuran, 7-phenol, carbofuran-3-keto, 3-
      hydroxycarbofuranphenol. For all compounds, the limit of detection was lower than
      0.1 ng mL(-1). Precision for all compounds, at the concentrations of 1, 10 and
      100 ng mL(-1) (n = 5) in-fortified urine samples ranged from 0.7% to 18%.
      Accuracy was calculated at two concentrations 8 and 80 ng mL(-1) (n = 5) and
      ranged from -8.4% to 8.2%. Relative recoveries at concentrations of 1, 10 and 100
      ng mL(-1), ranged from 71% to 116%. The method was successfully applied to five
      male applicators and 10 non-applicators (including both smokers and non-smokers).

PMID- 16442550
TI  - Gas chromatographic-mass spectrometric method for polycyclic aromatic hydrocarbon
      analysis in plant biota.
AB  - Using gas chromatography-mass spectrometry, a new method was developed for the
      identification and the quantification of polycyclic aromatic hydrocarbons (PAHs)
      in plants. This method was particularly optimised for PAH analyses in marine
      plants such as the halophytic species, Salicornia fragilis Ball et Tutin. The
      saponification of samples and their clean up by Florisil solid-phase extraction
      succeeded in eliminating pigments and natural compounds, which may interfere with
      GC-MS analysis. Moreover, a good recovery of the PAHs studied was obtained with
      percentages ranging from 88 to 116%. Application to the determination of PAH in a
      wide range of coastal halophytic plants is presented and validated the
      efficiency, the accuracy and the reproducibility of this method.

PMID- 16442551
TI  - Chiral separation and identification of beta-aminoketones of pharmacological
      interest by high performance liquid chromatography and capillary electrophoresis.
AB  - This paper describes the development and comparison of chiral methods of analysis
      for a series of pharmacologically active indane derivatives that have been
      studied in the context of the evaluation of a promising prodrug system for
      amines. The methods are intended for studying the differences in the
      pharmacokinetics of the optical isomers of these compounds. Capillary
      electrophoresis, using cyclodextrins as chiral selectors, and HPLC, using a
      Pirkle type stationary phase, were tested. Baseline separation was not achieved
      by HPLC, but good separations were obtained in less than 7 min, by capillary
      electrophoresis with phosphate buffers pH 2.5-3 using sulfated-beta-cyclodextrin
      or mixtures of neutral beta-cyclodextrins as chiral selectors.

PMID- 16442552
TI  - Dynamic ultrasound-assisted extraction of oleuropein and related biophenols from
      olive leaves.
AB  - A continuous approach for the ultrasound-assisted extraction of olive biophenols
      (OBPs) from olive leaves is proposed. Multivariate methodology was used to carry
      out a detailed optimisation of extraction. Under the optimal working conditions,
      complete extraction of the target analytes (namely, oleuropein, verbacoside,
      apigenin-7-glucoside and luteolin-7-glucoside with LODs 11.04, 2.68, 1.49 and
      3.91 mg/kg, respectively) was achieved in 25 min. The extract was injected into a
      chromatograph-photodiode array detector assembly (HPLC-DAD) for individual
      separation-quantification. No clean-up or preconcentration steps were required.
      Gas chromatography-mass spectrometry (without derivatization of the analytes) was
      used to identify OBPs at concentrations below the LODs obtained by HPLC-DAD. The
      efficacy of ethanol-water mixtures to extract OBPs from olive leaves has been
      demonstrated and compared with that of a conventional method which requires 24h
      for complete extraction; so these mixtures can substitute toxic extractants used
      to date.

PMID- 16442553
TI  - The synergistic effect between hydrophobic and electrostatic interactions in the
      uptake of amino acids by strongly acidic cation-exchange resins.
AB  - The goal of this work was to investigate the synergistic effect between the
      electrostatic and hydrophobic interactions upon the uptake of organic ions with
      hydrophobic moieties by ion-exchange resins with hydrophobic matrixes. The uptake
      of neutral amino acids by a macroporous polystyrene-based strongly acidic cation
      exchange resin (D001) and two strongly acidic cation-exchange resins (poly(2
      acrylamido-2-methyl propanesulfonic acid) and poly(vinylsulfonic acid)) with much
      less hydrophobic matrixes essentially follow an ion exchange stoichiometry.
      However, the thermodynamic parameters of the uptakes indicate that besides
      electrostatic interaction, hydrophobic interaction also contributes to the
      affinity of the amino acids with hydrophobic side chains for D001. No detectable
      uptake capacities for the amino acids by D001AM, which was obtained by amidation
      of the sulfonic acid groups of D001, can be determined. Thus, it is deduced that
      the hydrophobic interaction alone contributes little to the uptake of these amino
      acids by D001, of which hydrophobicity is the same with or lower than that of
      D001AM. These results indicate that synergistic effect exists between the
      electrostatic and hydrophobic interactions when the two interactions exist in a
      chelate manner and the hydrophobic interaction contributes to the uptake even if
      the hydrophobic interaction is so weak that it contributes little to the uptake
      when it acts alone.

PMID- 16442554
TI  - Separation of atropisomers of anti-hepatitis drug dimethyl diphenyl bicarboxylate
      analogues by capillary electrophoresis with vancomycin as the chiral selector.
AB  - Separation of atropisomers of analogues of the anti-hepatitis drug dimethyl
      diphenyl bicarboxylate (DDB) by capillary electrophoresis with vancomycin as the
      chiral selector is described. Among several tested chiral selectors, including
      various cyclodextrin derivatives as well as vancomycin, only the latter displayed
      the enantioselectivity to the studied atropisomers. However, relatively poor
      separation efficiency was obtained due to the adsorption of vancomycin on the
      capillary wall. This problem was overcome by modifying the capillary wall with a
      polycationic electrolyte named hexadimethrine bromide (HDB) to produce a
      positively charged coating, which minimized the adsorption of vancomycin on the
      capillary wall by electrostatic repulsion. Moreover, the positively charged
      coating could shorten the separation time by reversing the EOF because the
      reversed EOF migrated to the same direction as the negatively charged analyte.
      Effects of buffer pH, vancomycin and buffer concentrations and applied voltage on
      the separation were investigated and the optimal conditions were established as
      follows: 40 mM Tris-phosphate buffer (pH 6.0) containing 6.0 mM vancomycin and
      0.001% HDB. Baseline separation of three racemic DDB analogues was obtained
      within 12 min under the optimal conditions.

PMID- 16442555
TI  - A study on interfacial tension between flexible polymer and liquid crystal.
AB  - The interfacial property in polymer-liquid crystal systems is quite different
      from flexible polymer-polymer mixtures due to the anisotropic properties of
      liquid crystals. The apparent interfacial tension between a liquid crystal and a
      flexible polymer was measured by deformed droplet retraction method. The
      deformation and recovery of a single liquid crystal droplet dispersed in a
      poly(dimethylsiloxane) matrix were realized by a transient shear flow and
      observed by polarized optical microscope. The apparent interfacial tension of
      polymer-liquid crystal system was found to be greatly dependent on the
      temperature, initial droplet deformation and liquid crystal droplet size.

PMID- 16442556
TI  - Interface of AOT/Brij mixed reverse micellar systems: conductometric and
      spectrophotometric investigations.
AB  - Solubilization and conductivity studies are carried out with AOT/Brijs (Brij-30,
      Brij-35, Brij-52, Brij-56, Brij-58, Brij-72, Brij-76, Brij-78)/isooctane/water
      mixed reverse micellar systems. Replacement of AOT molecules with large head
      group Brij molecules (Brij-30, Brij-35, Brij-56, Brij-58, Brij-76, Brij-78)
      decreases the solubilization capacity, whereas those with smaller polar head
      groups (Brij-52 and Brij-72) increases it. The former blends assist the
      conductance percolation whereas the latter retard it. An attempt has been taken
      to obtain more insight on the interfacial composition of the mixed interface with
      the help of spectrophotometric studies using 7-hydroxycoumarin as the
      fluorophore. The results obtained from the solubilization and conductometric
      studies have been correlated with those obtained from the spectroscopic studies.

PMID- 16442557
TI  - Characteristics of phenol and chlorinated phenols sorption onto surfactant
      modified bentonite.
AB  - Surfactant-modified bentonite was synthesized by replacing adsorbed Na+ with long
      chain alkyl quaternary ammonium cation, hexadecyltrimethylammonium bromide
      (HDTMAB). The sorption isotherms of phenol, p-chlorophenol, and 2,4
      dichlorophenol were modeled according to the Langmuir and Freundlich equations.
      The Langmuir isotherm was found to describe the equilibrium adsorption data well.
      The mechanisms and characteristics of sorption of these ionizable organic
      contaminants onto surfactant-modified bentonite from water were investigated
      systematically and described quantitatively. The sorption properties are affected
      by the treatment conditions, such as amount of organobentonite, and the
      properties of organic compounds. Results indicated that adsorption of phenols
      from water was in proportion to their hydrophobicities, which increased with
      chlorine addition (phenol<p-chlorophenol<2,4-dichlorophenol). Sorption isotherms
      of these phenols were typically nonlinear. Both adsorption and partition
      contribute to the sorption of investigated phenols to organobentonite. The
      separate contributions of adsorption and partition to the total sorption of these
      compounds to organobentonite is analyzed mathematically. Results indicate that
      the partition effect is weak and linear with contaminant concentration, whereas
      the adsorption effect is more powerful and nonlinear with contaminant
      concentration. The sorption of phenols onto organobentonite was dominated by
      adsorption at low concentrations and partition started to dominate at high
      concentrations, making the organobentonites powerful sorbents for organic
      contaminants over a wide range of concentrations.

PMID- 16442558
TI  - Some empirical observations about early stuttering: a possible link to language
      development.
AB  - This article suggests a possible link between incipient stuttering and early
      difficulty in language formulation. The hypothesis offers a unifying explanation
      of an array of empirical observations. Among these observations are the
      following: early stuttering occurs only on the first word of a syntactic
      structure; stuttering does not appear to be influenced by word-related factors;
      early stuttering seldom occurs on one-word utterances; the earliest age at which
      stuttering is reported is 18 months, with the beginning of grammatical
      development; the age at which most onset of stuttering is reported, 2-5 years,
      coincides with the period during which children acquire syntax; considerable
      spontaneous recovery takes place at the time most children have mastered syntax;
      incipient stuttering is influenced by the length and grammatical complexity of
      utterances; young children who stutter may be somewhat deficient in language
      skills; boys who stutter outnumber girls. LEARNING OUTCOMES: The reader will
      learn about a number of empirical observations about incipient stuttering and how
      they may be explained by a syntax-based hypothesis about its etiology.

PMID- 16442559
TI  - A pattern of anti-carbohydrate antibody responses present in patients with
      advanced atherosclerosis.
AB  - We have previously shown that an antibody pool present in normal human serum
      binds cytokine receptors in vitro and may therefore interfere with assays that
      capture cytokines using their receptors. Here we show that this antibody pool is
      the same as the natural antibody termed anti-gal, that binds to the alpha
      galactosyl carbohydrate epitope (alpha-gal) and which is the predominant obstacle
      to xenotransplantation. We report that there are high levels of IgD anti alpha
      gal in most volunteers, in addition to the IgG2, IgA and IgM immunoglobulin
      isotypes against alpha-gal previously described. To determine if anti-gal may
      interfere with assays that depend on capture of cytokine with its receptor, we
      measured levels of several anti-carbohydrate antibodies in a cohort of patients
      with advanced atherosclerosis that had previously been used to measure levels of
      active TGF-beta using such an assay. For many isotype / carbohydrate
      combinations, there is a large and significant difference between the levels of
      anti-carbohydrate antibodies in patients with atherosclerosis and controls, after
      adjustment for age, sex and blood group. These results are similar to the
      previous data obtained for active TGF-beta, and therefore we cannot discount the
      possibility that anti-gal contributed to the previous data. Following further
      adjustment for several risk factors associated with cardiovascular disease,
      several anti-carbohydrate antibodies were still significantly different between
      patients and controls. Therefore, anti-carbohydrate antibodies may represent a
      new class of risk factors that may be associated with presence of advanced
      atherosclerosis, although larger studies will be required to confirm this
      hypothesis.

PMID- 16442560
TI  - Direct selection of antibodies from complex libraries with the protein fragment
      complementation assay.
AB  - The aim of the present study was to develop the protein fragment complementation
      assay (PCA) for the intracellular selection of specific binding molecules from
      the fully synthetic HuCAL antibody library. Here, we describe the first
      successful selections of specific antibodies by PCA, and we discuss the
      opportunities and limitations of this approach. First, we enriched an antibody
      specific for the capsid protein D of bacteriophage lambda (gpD) by ten successive
      rounds of competitive liquid culture selection. In an independent approach, we
      selected a specific antibody for the c-Jun N-terminal kinase 2 (JNK2) in a single
      step selection setup. In order to obtain specific antibodies in only a single PCA
      selection round, the selection system was thoroughly investigated and several
      strategies to reduce the amount of false positives were evaluated. When expressed
      in the cytoplasm of Escherichia coli, the PCA-selected scFv antibody fragments
      could be purified as soluble and monomeric proteins. Denaturant-induced unfolding
      experiments showed that both antibody fragments are stable molecules, even when
      the disulfide bonds are reduced. Furthermore, antigen-specificity of the PCA
      selected antibody fragments is demonstrated by in vivo and in vitro experiments.
      As antigen binding is retained regardless of the antibody redox state, both PCA
      selected antibody fragments can tolerate the loss of disulfide bridge formation.
      Our results illustrate that it is possible to select well-expressed, stable,
      antigen-specific, and intracellular functional antibodies by PCA directly.

PMID- 16442561
TI  - Shape of the free energy barriers for protein folding probed by multiple
      perturbation analysis.
AB  - The characterization of the free energy barriers has been a major goal in studies
      on the mechanism of protein folding. Testing the effect of mutations or
      denaturants on protein folding reactions revealed that transition state movement
      is rare, suggesting that folding barriers are robust and narrow maxima on the
      free energy landscape. Here we demonstrate that the application of multiple
      perturbations allows the observation of small transition state movements that
      escape detection in single perturbation experiments. We used tendamistat as a
      model protein to test the broadness of the free energy barriers. Tendamistat
      folds over two consecutive transition states and through a high-energy
      intermediate. Measuring the combined effect of temperature and denaturant on the
      position of the transition state in the wild-type protein and in several mutants
      revealed that the early transition state shows significant transition state
      movement. Its accessible surface area state becomes more native-like with
      destabilization of the native state by temperature. To the same extent, the
      entropy of the early transition state becomes more native-like with increasing
      denaturant concentration, in accordance with Hammond behavior. The position of
      the late transition state, in contrast, is much less sensitive to the applied
      perturbations. These results suggest that the barriers in protein folding become
      increasingly narrow as the folding polypeptide chain approaches the native state.

PMID- 16442562
TI  - Comparative effects of alpha-tocopherol and gamma-tocotrienol against hydrogen
      peroxide induced apoptosis on primary-cultured astrocytes.
AB  - Oxidative stress is thought to be one of the factors that cause neurodegeneration
      and that this can be inhibited by antioxidants. Since astrocytes support the
      survival of central nervous system (CNS) neurons, we compared the effect of alpha
      tocopherol and gamma-tocotrienol in minimizing the cytotoxic damage induced by
      H(2)O(2), a pro-oxidant. Primary astrocyte cultures were pretreated with either
      alpha-tocopherol or gamma-tocotrienol for 1 h before incubation with 100 microM
      H(2)O(2) for 24 h. Cell viability was then assessed using the MTS assay while
      apoptosis was determined using a commercial ELISA kit as well as by fluorescent
      staining of live and apoptotic cells. The uptake of alpha-tocopherol and gamma
      tocotrienol by astrocytes were also determined using HPLC. Results showed that
      gamma-tocotrienol is toxic at concentrations >200 microM but protects against
      H(2)O(2) induced cell loss and apoptosis in a dose dependent manner up to 100
      microM. alpha-Tocopherol was not cytotoxic in the concentration range tested (up
      to 750 microM), reduced apoptosis to the same degree as that of gamma-tocotrienol
      but was less effective in maintaining the viable cell number. Since the uptake of
      alpha-tocopherol and gamma-tocotrienol by astrocytes is similar, this may reflect
      the roles of these 2 vitamin E subfamilies in inhibiting apoptosis and
      stimulating proliferation in astrocytes.

PMID- 16442563
TI  - Pathology of the sympathetic nervous system corresponding to the decreased
      cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient
      with Parkinson disease.
AB  - Decreased cardiac uptake in (123)I-metaiodobenzylguanidine (MIBG) scintigraphy
      has been adopted as one of the most reliable diagnostic tests for Parkinson
      disease (PD) in Japan. To investigate the morphological basis for this finding,
      we performed a detailed neuropathological study of the cardiac sympathetic
      nervous system of a 71-year-old autopsy-proven PD patient, who presented with a
      marked decrease in cardiac uptake of MIBG, just 1 year prior to death. We
      carefully examined the intermediolateral column at several levels of the thoracic
      spinal cord, the sympathetic trunk and ganglia, and the nerve plexus of the
      anterior wall of the left ventricle and compared the findings with those of five
      age-matched controls. We found that the cardiac plexus was more heavily involved
      than the sympathetic ganglia in this patient with PD. Our study may provide
      further evidence that the markedly decreased cardiac uptake of MIBG observed in
      PD cases represents preferential involvement of the cardiac sympathetic nerve
      plexus in this disorder.

PMID- 16442564
TI  - A mathematical and experimental study of ant foraging trail dynamics.
AB  - In this article, we present a mathematical model coupled to an experimental study
      of ant foraging trails. Our laboratory experiments on Tetramorium caespitum do
      not find a strong relationship between ant densities and velocities, a common
      assumption in traffic modeling. Rather, we find that higher order effects play a
      major role in observed behavior, and our model reflects this by including
      inertial terms in the evolution equation. A linearization of the resulting system
      yields left- and right-moving waves, in agreement with laboratory measurements.
      The linearized system depends upon Froude numbers reflecting a ratio of the
      energy stored in the foraging trail to the kinetic energy of the ants. The model
      predicts and the measurements support the existence of two distinct phase
      velocities.

PMID- 16442565
TI  - The probable structure of the protamine-DNA complex.
AB  - A detailed molecular structure is proposed for the human protamine-DNA complex,
      which has hitherto been largely a mystery. The structure was created with virtual
      modeling software (AmiraMol), employing logical deduction as the primary
      investigative tool. A beta-sheet structure for the protein component is
      essentially mandated, as the alternatives can be decisively excluded. A dimeric
      structure too is essentially mandated, since the cysteine residues of protamines
      P1 and P2 are invariably aligned in all species having both chains. The cross
      sectional and axial spacings of arginine guanidinium groups in this protein
      structure can be perfectly aligned with those of phosphate groups in DNA
      according to the DNA structure proposed by Wu. This is a non-helical structure,
      whose possible occurrence in certain plasmids has been suggested by experimental
      observations. The unit cell of this protamine-DNA complex is essentially devoid
      of steric hindrances, and heavily favored by a multitude of ionic and hydrogen
      bonds. The packing of adjacent "unit cells" of the protamine-DNA structure is
      based on a complex array of salt bridges, the mere existence of which is so
      fortuitous that it is virtually inconceivable that it comes about through a mere
      modeling "coincidence". The possible significance of the structure beyond the
      sperm cell is discussed.

PMID- 16442566
TI  - Within-host evolution and virulence in microparasites.
AB  - An important aspect of microparasite biology is the fact that infections are
      populations of thousands of microbes. As any population, infections are hence
      subject to two main types of changes: demographic and evolutionary. Here we
      analyse the consequences of within-host evolutionary changes. We build an
      epidemiological model where infections are regularly invaded by locally favored
      mutations affecting various infectious traits (virulence, transmissibility and
      clearance). Our results are the following. In durable infections, where within
      host evolution is an important matter, a drop of transmissibility is only
      slightly deleterious to the infection, while a reduction of infection lifespan is
      very costly. In consequence, locally favored mutations reducing transmissibility
      reach a larger frequency, or even the complete fixation, and the suboptimality
      accumulated in infections owing to within-host evolution affects more their
      transmission than their duration. Conversely, taking an infection at random and
      observing the events of within-host evolution, one is more likely to observe
      reductions of infection length than reductions of transmissibility, because the
      mutations affecting transmissibility are often already present in infections. We
      then discuss the interpretation of these results in terms of deleterious
      mutations, and we also emphasize that the management of within-host evolution
      could be used as a novel therapeutic approach to the treatment of infection.

PMID- 16442568
TI  - Multiple attractors in host-parasitoid interactions: coexistence and extinction.
AB  - This paper considers the dynamics of a two-dimensional discrete-time model for
      host-parasitoid interactions, and shows that the model has two attractors: the
      fixed point where two species coexist and a boundary cycle where the parasitoid
      is absent. The analysis with the Liapunov exponent confirms that this kind of
      bistability is common in this model. The generality of this phenomenon in host
      parasitoid interactions is also discussed.

PMID- 16442567
TI  - Endometrium estradiol receptors type I and type II during early pregnancy of rat.
AB  - By centrifugation in a sucrose density gradient we studied the citosol 17beta
      estradiol binding sites of blastocyst receptive and non-receptive endometrial
      zones, as well as uterine horn endometrium whose ovary was extirpated three weeks
      before pregnancy. The cytosol was prelabelled with [3H]-17beta-estradiol 2 and 25
      nM. In this work two incubation temperatures were studied. On the other hand, at
      4 degrees C unoccupied receptors were identified as different from the classic
      receptor 8S type I. At the same time, we found that 25 degrees C is the optimal
      temperature for the assay of total receptors to achieve complete exchange of [3H]
      17beta-estradiol by 17beta-estradiol in the binding sites. In these conditions,
      the major component was the 4S type II receptor, mainly in the endometrium from
      ovariectomized uteri. Furthermore, 17beta-estradiol content was determined in the
      total homogenized by radioimmunoassay and the results were: 1.42+/-0.16, 1.22+/
      0.15 and 1.75+/-0.27 pmol/g wet tissue for receptive, non-receptive and
      ovariectomized uteri, respectively.

PMID- 16442569
TI  - Comparative Mouse Genomics Centers Consortium: the Mouse Genotype Database.
AB  - The Comparative Mouse Genomics Centers Consortium (CMGCC) is a branch of the
      Environmental Genome Project sponsored by the National Institute of Environmental
      Health Sciences (NIEHS) focusing upon the identification of human single
      nucleotide polymorphisms (SNPs) that may confer disease susceptibility within the
      human population. The goal of the CMGCC (http://www.niehs.nih.gov/cmgcc/) is to
      make genetic mouse models for human SNPs within cell cycle control, DNA
      replication and DNA repair genes that may be associated with human pathologies.
      In order to facilitate information sharing and analysis within the consortium a
      set of informatics resources have been generated to support the mouse model
      development efforts. The primary entry point for information about the mouse
      models developed by the consortium is through the CMGCC Genotype Database
      (http://mrages.niehs.nih.gov/genotype/), which maintains both a consortium
      specific and public access display of the available and developing mouse models.

PMID- 16442570
TI  - Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent
      sulforaphane found in broccoli, induces phase-I xenobiotic metabolizing enzymes
      and increases free radical generation in rat liver.
AB  - Epidemiological and animal studies linking high fruit and vegetable consumption
      to lower cancer risk have strengthened the belief that long-term administration
      of isolated naturally occurring dietary constituents could reduce the risk of
      cancer. In recent years, metabolites derived from phytoalexins, such as
      glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae),
      have gained much attention as potential cancer chemopreventive agents. The
      protective effect of these micronutrients is assumed to be due to the inhibition
      of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II
      detoxifying enzymes, an assumption that still remains uncertain. The protective
      effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate
      metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver,
      that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts
      Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs),
      nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms
      CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP
      induction was paralleled by an increase in the corresponding mRNA levels.
      Concomitant with this Phase-I induction, we also found that glucoraphanin
      generated large amount of various reactive radical species, as determined by
      electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe
      technique. This suggests that long-term uncontrolled administration of
      glucoraphanin could actually pose a potential health hazard.

PMID- 16442571
TI  - Homologous recombination in plants is organ specific.
AB  - In this paper we analysed the genome stability of various Arabidopsis thaliana
      plant organs using a transgenic recombination system. The system was based on two
      copies of non-functional GUS (lines #651 and #11) or LUC (line #15D8) reporter
      genes serving as a recombination substrate. Both reporter assays showed that
      recombination in flowers or stems were rare events. Most of the recombination
      sectors were found in leaves and roots, with leaves having over 2-fold greater
      number of the recombination events per single cell genome as compared to roots.
      The recombination events per single genome were 9.7-fold more frequent on the
      lateral half of the leaves than on the medial halves. This correlated with a 2.5
      fold higher metabolic activity in the energy source (lateral) versus energy sink
      (medial) of leaves. Higher metabolic activity was paralleled by a higher
      anthocyanin production in lateral halves. The level of double strand break (DSB)
      occurrence was also different among plant organs; the highest level was observed
      in roots and the lowest in leaves. High level of DSBs strongly positively
      correlated with the activity of the key repair enzymes, AtKU70 and AtRAD51. The
      ratio of AtRAD51 to AtKU70 expression was the highest in leaves, supporting the
      more active involvement of homologous recombination pathway in the repair of DSBs
      in this organ. Western blot analysis confirmed the real time PCR expression data
      for AtKU70 gene.

PMID- 16442572
TI  - Weight suppression predicts weight gain during inpatient treatment of bulimia
      nervosa.
AB  - Bulimic individuals typically lose a substantial amount of weight in the process
      of developing their disorder. Such weight suppression (WS) may be behaviorally
      and metabolically problematic. The present study tested the hypothesis that WS
      would predict weight gain during the inpatient hospitalization of 146 bulimia
      nervosa-spectrum inpatients. WS represented the difference (M=12.0 kg) between
      highest weight ever and current body weight. Controlling for length of stay and
      current dieting (EAT-D scores), high levels of WS predicted greater weight gain.
      Furthermore, WS and admission BMI independently predicted weight gain when
      entered together in a regression analysis. Weight gain was also related to
      clinical improvement. These findings suggest that weight suppression,
      independently of current dieting status, may produce psychobiological pressures
      toward weight gain and could complicate the treatment of bulimia nervosa.

PMID- 16442573
TI  - Purification and primary structure determination of two Bowman-Birk type trypsin
      isoinhibitors from Cratylia mollis seeds.
AB  - Two Bowman-Birk type trypsin inhibitors (CmTI(1) and CmTI(2)) were purified from
      Cratylia mollis seeds by acetone precipitation, ion exchange, gel filtration and
      reverse-phase chromatography. CmTI(1) and CmTI(2), with 77 and 78 amino acid
      residues, respectively, were sequenced in their entirety and show a high
      structural similarity to Bowman-Birk inhibitors from other Leguminosae. The
      putative reactive sites of CmTI(1) are a lysine residue at position 22 and a
      tyrosine residue at position 49. Different reactive sites, as identified by their
      alignment with related inhibitors, were found for CmTI(2): lysine at position 22
      and leucine at position 49. The dissociation constant K(i) of the complex with
      trypsin is 1.4 nM. The apparent molecular mass is 17 kDa without DDT and 11 kDa
      with reducing agent and heating.

PMID- 16442574
TI  - PeroxiBase: a class III plant peroxidase database.
AB  - Class III plant peroxidases (EC 1.11.1.7), which are encoded by multigenic
      families in land plants, are involved in several important physiological and
      developmental processes. Their varied functions are not yet clearly determined,
      but their characterization will certainly lead to a better understanding of plant
      growth, differentiation and interaction with the environment, and hence to many
      exciting applications. Since there is currently no central database for plant
      peroxidase sequences and many plant sequences are not deposited in the
      EMBL/GenBank/DDBJ repository or the UniProt KnowledgeBase, this prevents
      researchers from easily accessing all peroxidase sequences. Furthermore, gene
      expression data are poorly covered and annotations are inconsistent. In this
      rapidly moving field, there is a need for continual updating and correction of
      the peroxidase superfamily in plants. Moreover, consolidating information about
      peroxidases will allow for comparison of peroxidases between species and thus
      significantly help making correlations of function, structure or phylogeny. We
      report a new database (PeroxiBase) accessible through a web server with specific
      tools dedicated to facilitate query, classification and submission of peroxidase
      sequences. Recent developments in the field of plant peroxidase are also
      mentioned.

PMID- 16442575
TI  - Rings B,D-seco limonoids from the leaves of Swietenia mahogani.
AB  - Seven phragmalin limonoids of swietephragmins A-G, and two other different types
      of 2-hydroxy-3-O-tigloylswietenolide and deacetylsecomahoganin, were isolated
      along with three known limonoids from the leaves of Swietenia mahogani
      (Meliaceae). Their structures were determined by spectroscopic methods.

PMID- 16442576
TI  - Newbouldiaquinone A: A naphthoquinone-anthraquinone ether coupled pigment, as a
      potential antimicrobial and antimalarial agent from Newbouldia laevis.
AB  - The study of the chemical constituents of the roots of Newbouldia laevis
      (Bignoniaceae) has resulted in the isolation and characterization of a
      naphthoquinone-anthraquinone coupled pigment named newbouldiaquinone A (1)
      together with 14 known compounds: apigenin, chrysoeriol, newbouldiaquinone,
      lapachol, 2-methylanthraquinone, 2-acetylfuro-1,4-naphthoquinone, 2,3-dimethoxy
      1,4-benzoquinone, oleanolic acid, canthic acid, 2-(4-hydroxyphenyl)ethyl
      triacontanoate, newbouldiamide, 5,7-dihydroxydehydroiso-alpha-lapachone, beta
      sitosterol, and beta-sitosterol glucopyranoside. The structure elucidation of the
      isolated compounds was established based on spectroscopic studies, notably of the
      2D NMR spectra. The antimalarial activity of compound (1) against Plasmodium
      falciparum in vitro shows moderate chemo suppression of parasitic growth. Its
      antimicrobial activity against a wide range of microorganisms was 13- and 24-fold
      more active against Candida gabrata and Enterobacter aerogens than the reference
      antibiotics nystatin and gentamycin.

PMID- 16442577
TI  - First evidence of pfcrt mutant Plasmodium falciparum in Madagascar.
AB  - The island of Madagascar, lying in the Indian Ocean approximately 250 miles from
      the African coast, has so far remained one of the few areas in the world without
      noticeable Plasmodium falciparum high-grade chloroquine (CQ) resistance. Here we
      report genotyping data on pfcrt in Madagascar. The pfcrt K76T mutation, which is
      critical for resistance to CQ, was detected in six (3.3%) of 183 P. falciparum
      isolates screened, within the mutant haplotypes CVIET and CVIDT. This is the
      first observation of pfcrt mutant parasites on the island. The current massive
      distribution of CQ for in-home management of fever in children will promote the
      dissemination of these mutant CQ-resistant parasites. In this context, genotyping
      of pfcrt remains a useful tool for CQ resistance surveillance as the prevalence
      of pfcrt mutations is far from saturation in Madagascar.

PMID- 16442579
TI  - Spatially structured superinfection and the evolution of disease virulence.
AB  - When pathogen strains differing in virulence compete for hosts, spatial
      structuring of disease transmission can govern both evolved levels of virulence
      and patterns in strain coexistence. We develop a spatially detailed model of
      superinfection, a form of contest competition between pathogen strains; the
      probability of superinfection depends explicitly on the difference in levels of
      virulence. We apply methods of adaptive dynamics to address the interplay of
      spatial dynamics and evolution. The mean-field approximation predicts evolution
      to criticality; any small increase in virulence capable of dynamical persistence
      is favored. Both pair approximation and simulation of the detailed model indicate
      that spatial structure constrains disease virulence. Increased spatial clustering
      reduces the maximal virulence capable of single-strain persistence and, more
      importantly, reduces the convergent-stable virulence level under strain
      competition. The spatially detailed model predicts that increasing the
      probability of superinfection, for given difference in virulence, increases the
      likelihood of between-strain coexistence. When strains differing in virulence can
      coexist ecologically, our results may suggest policies for managing diseases with
      localized transmission. Comparing equilibrium densities from the pair
      approximation, we find that introducing a more virulent strain into a host
      population infected by a less virulent strain can sometimes reduce total host
      mortality and increase global host density.

PMID- 16442578
TI  - Estimation of the prevalence of lymphatic filariasis by a pool screen PCR assay
      using blood spots collected on filter paper.
AB  - The prevalence of lymphatic filariasis was estimated by PCR-based pool screening
      of night blood collected from 865 individuals living in ten areas endemic for
      Wuchereria bancrofti, Brugia malayi or B. timori in Indonesia. A total of 232
      microfilaraemics were identified by filtration of 1 ml of blood. The microfilaria
      (mf) prevalence ranged from 6% to 54%, and the mf density in microfilaraemics
      ranged from 1 mf/ml to 6028 mf/ml. PCR assays both for W. bancrofti or Brugia
      spp. detected a single mf present on a 30 microl dried filter paper blood spot.
      One hundred and seventy-eight pools of five blood spots in each pool (pool-5)
      were tested by PCR and 101 (57%) pools were positive. When pool size was
      increased to 10 spots per pool (pool-10), 65 (70%) of 93 pools were positive.
      Pearson's correlation and linear regression showed a strong correlation between
      filtration and pool screen PCR results for pool-10 (r=0.835) and pool-5
      (r=0.695). Based on the determination coefficient (R), the results of pool-10 PCR
      (R=0.697) gave a better prediction compared with pool-5 PCR (R=0.483). This study
      suggests that pool screen PCR may be a useful tool for monitoring the Global
      Program to Eliminate Lymphatic Filariasis.

PMID- 16442580
TI  - Virulence and pathogenesis of the MSW and MSD strains of Californian myxoma virus
      in European rabbits with genetic resistance to myxomatosis compared to rabbits
      with no genetic resistance.
AB  - The pathogenesis of two Californian strains of myxoma virus (MSW and MSD) was
      examined in European rabbits (Oryctolagus cuniculus) that were either susceptible
      to myxomatosis (laboratory rabbits) or had undergone natural selection for
      genetic resistance to myxomatosis (Australian wild rabbits). MSW was highly
      lethal for both types of rabbits with average survival times of 7.3 and 9.4 days,
      respectively, and 100% mortality. Classical clinical signs of myxomatosis were
      not present except in one rabbit that survived for 13 days following infection.
      Previously described clinical signs of trembling and shaking were observed in
      laboratory but not wild rabbits. Despite the high resistance of wild rabbits to
      myxomatosis caused by South American strains of myxoma virus, the MSW strain was
      of such high virulence that it was able to overcome resistance. The acute nature
      of the infection, relatively low viral titers in the tissues and destruction of
      lymphoid tissues, suggested that death was probably due to an acute and
      overwhelming immunopathological response to the virus. No virus was found in the
      brain. The MSD strain was attenuated compared to previously published
      descriptions and therefore was only characterized in laboratory rabbits. It is
      concluded that Californian MSW strain of myxoma virus is at the extreme end of a
      continuum of myxoma virus virulence but that the basic pathophysiology of the
      disease induced is not broadly different to other strains of myxoma virus.

PMID- 16442581
TI  - A domain directly C-terminal to the major homology region of human
      immunodeficiency type 1 capsid protein plays a crucial role in directing both
      virus assembly and incorporation of Gag-Pol.
AB  - We demonstrate here that a deletion of 14 amino acid residues directly C-terminal
      to the major homology region (MHR) of the HIV-1 capsid (CA) in Gag-Pol markedly
      affects the incorporation of Gag-Pol into virions. The 14-amino acid deletion
      also significantly impaired virus assembly. In agreement with previous reports,
      mutations at the very C-terminus of CA resulted in a remarkable reduction in
      virus production. However, HIV-1 Gag-Pol precursors containing the C-terminal CA
      mutation were still capable of being incorporated into virions at a level of
      about 50% that of the wild-type. These results suggest that the domain
      immediately C-terminal to the MHR is functionally involved in Gag-Gag and Gag/Gag
      Pol interaction, and this supports the notion that Gag or Gag-Pol mutants blocked
      in assembly into virus particles can be rescued into virions provided they retain
      the domains that are able to interact with the Gag precursor. An HIV-1 Gag-Pol
      deletion mutant retaining a minimal sequence consisting of the MHR and the
      adjacent CA-SP1 was efficiently incorporated into virions. Analysis by
      immunofluorescence staining indicated that the subcellular localization patterns
      shown by the Gag-Pol mutants were not fully compatible with their efficiency in
      being incorporated into virions, suggesting that the ability of Gag-Pol mutants
      to be incorporated into virions largely depends on their interactions with the
      Gag precursor.

PMID- 16442582
TI  - Discrete stimulus estimation from neural responses in the turtle retina.
AB  - In this paper, we investigate the decoding of flashed, full-field visual stimuli
      while recording from a population of retinal ganglion cells. We present a direct
      statistical method for determining the likelihood that a response was evoked by a
      particular stimulus, and use this method to estimate stimuli based on
      microelectrode array recordings in the turtle retina. This method uses the well
      known time-varying Poisson model of neural firing, along with extensions to
      accommodate neural refractory periods. Unlike other approaches commonly used for
      Poisson processes, the specific formulation presented here is bin free and
      requires few user-specified parameters. Statistical dependency issues and the
      effects of stationarity on the estimation method are also discussed.

PMID- 16442583
TI  - Ultrasonic control of ceramic membrane fouling: Effect of particle
      characteristics.
AB  - In this study, the effect of particle characteristics on the ultrasonic control
      of membrane fouling was investigated. Ultrasound at 20 kHz was applied to a cross
      flow filtration system with gamma-alumina membranes in the presence of colloidal
      silica particles. Experimental results indicated that particle concentration
      affected the ability of ultrasound to control membrane fouling, with less
      effective control of fouling at higher particle concentrations. Measurements of
      sound wave intensity and images of the cavitation region indicated that particles
      induced additional cavitation bubbles near the ultrasonic source, which resulted
      in less turbulence reaching the membrane surface and subsequently less effective
      control of fouling. When silica particles were modified to be hydrophobic,
      greater inducement of cavitation bubbles near the ultrasonic source occurred for
      a fixed concentration, also resulting in less effective control of fouling.
      Particle size influenced the cleaning ability of ultrasound, with better permeate
      recovery observed with larger particles. Particle size did not affect sound wave
      intensity, suggesting that the more effective control of fouling by large
      particles was due to greater lift and cross-flow drag forces on larger particles
      compared to smaller particles.

PMID- 16442584
TI  - Estimating the combined effects of copper and phenol to nitrifying bacteria in
      wastewater treatment plants.
AB  - The inhibition of nitrification by phenol and copper mixtures was studied to
      investigate the differences between individual and mixture inhibition as the
      change of phenol and copper speciation due to their reactions. This study showed
      a decrease in the ammonium removal rate (k, first-order rate coefficient),
      indicating an increase in the relative % inhibition on nitrification, as the
      phenol and mixed liquor suspended solids (MLSS) concentrations were increased. In
      the case of copper, the ammonium removal rate decreased as the copper
      concentration increased and that of the MLSS decreased. This was attributed to
      the enhanced sorption of copper to heterotrophs at high MLSS concentrations. The
      relative % inhibition was plotted against free Cu2+ ions, which showed a close
      relationship. In the tests on copper and phenol mixtures, the mixture effects
      turned out overestimated by the calculation based on the additional chemical
      concentrations. In most Cu-phenol mixture tests, the presence of phenol as a
      complexation ligand caused a reduction of the inhibition rate to nitrifiers over
      the entire exposure range. Consequently, the prediction of nitrification
      inhibition in mixture environments, such as wastewater treatment plants, is
      influenced by the presence of a number of parameters that affect the activity of
      nitrifiers and, therefore, chemical speciation should be taken into
      consideration.

PMID- 16442585
TI  - Definition and GIS-based characterization of an integral risk index applied to a
      chemical/petrochemical area.
AB  - A risk map of the chemical/petrochemical industrial area of Tarragona (Catalonia,
      Spain) was designed following a two-stage procedure. The first step was the
      creation of a ranking system (Hazard Index) for a number of different inorganic
      and organic pollutants: heavy metals, polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polychlorinated
      aromatic hydrocarbons (PAHs) by applying self-organizing maps (SOM) to
      persistence, bioaccumulation and toxicity properties of the chemicals. PCBs
      seemed to be the most hazardous compounds, while the light PAHs showed the
      minimum values. Subsequently, an Integral Risk Index was developed taking into
      account the Hazard Index and the concentrations of all pollutants in soil samples
      collected in the assessed area of Tarragona. Finally, a risk map was elaborated
      by representing the spatial distribution of the Integral Risk Index with a
      geographic information system (GIS). The results of the present study seem to
      indicate that the development of an integral risk map might be useful to help in
      making-decision processes concerning environmental pollutants.

PMID- 16442586
TI  - Tidal salt marsh sediment in California, USA. Part 1: occurrence and sources of
      organic contaminants.
AB  - Surface sediment samples (0-5 cm) from five tidal marshes along the coast of
      California, USA were analyzed for organic pollutants to investigate their
      relationship to land use, current distribution within marshes, and possible
      sources. Among the study areas, Stege Marsh, located in San Francisco Bay, was
      the most contaminated. Compared to San Francisco Bay, Stege Marsh had much higher
      levels of organic contaminants such as PCBs (polychlorinated biphenyls), DDTs,
      and chlordanes. At reference marshes (Tom's Point and Walker Creek in Tomales
      Bay), organic contaminants in sediments were very low. While PAHs (polycyclic
      aromatic hydrocarbons) were found at all of the study areas (22-13,600 ng g(-1)),
      measurable concentrations of PCBs were found only in the sediments from Stege
      Marsh (80-9,940 ng g(-1)). Combustion related (pyrogenic) high molecular weight
      PAHs were dominant in sediments from Stege and Carpinteria Marshes, while in
      sediments from Tom's Point and Walker Creek petroleum related (petrogenic) low
      molecular weight PAHs and alkyl-substituted PAHs were much more abundant than
      pyrogenic PAHs. PCB congener patterns in all of the Stege Marsh samples were the
      same and revealed that Aroclor 1248 was a predominant source. In all marshes, the
      sum of DDE and DDD accounted for more than 90% of total DDTs, indicating that DDT
      has degraded significantly. The ratios of p,p'-DDE to p,p'-DDD in sediments from
      Stege Marsh provide evidence of possible previous use of technical DDD. Chlordane
      ratios indicated that chlordanes have degraded slightly. Bis(2
      ethylhexyl)phthalate (280-32,000 ng g(-1)) was the most abundant phthalate. The
      data indicates that Stege Marsh may be a source of contaminants that continue to
      be discharged into San Francisco Bay.

PMID- 16442587
TI  - Bears and humans in Chauvet Cave (Vallon-Pont-d'Arc, Ardeche, France): insights
      from stable isotopes and radiocarbon dating of bone collagen.

PMID- 16442588
TI  - Effects of acute exercise on lung antioxidant enzymes in young and old rats.
AB  - The lung could be the target organ to cellular damage, since it is directly
      exposed to high concentrations of oxygen. Acute exercise and age would be an
      added challenge to the lung, and therefore, we investigated alterations of major
      lung antioxidant enzymes (manganese-superoxide dismutase, Mn-SOD; copper-zinc
      SOD, Cu-Zn-SOD; glutathione peroxidase, GPX; catalase, CAT) activities and mRNA
      expressions in young (4 months old) and old (26 months old) male Wistar rats with
      exercise. Thioredoxin reductase (TrxR) activity was also investigated. Mn-SOD and
      Cu-Zn-SOD increased with age, but age did not affect GPX, CAT, or TrxR activity.
      Acute exercise in young animals increased the activities of Mn-SOD, Cu-Zn-SOD,
      and CAT. In contrast, only Mn-SOD increased significantly in the old animals. The
      mRNA expressions of Mn-SOD, Cu-Zn-SOD and GPX were not altered with age, while
      CAT mRNA expression decreased with age. Acute exercise had no significant effect
      on any of the antioxidant enzyme mRNA expression. Moreover, reactive carbonyl
      derivative increased with age, but no significant changes were detected after
      acute exercise in either group. In summary, antioxidant enzymes responsible for
      the removal of hydrogen peroxide were unable to increase their enzyme activities
      in the old animals with exercise.

PMID- 16442590
TI  - Lead and cadmium exposures from canned and non-canned beverages in Nigeria: a
      public health concern.
AB  - The lead and cadmium levels of canned and non-canned foods purchased in Nigeria
      were studied. Fifty samples of these beverages were digested in nitric acid and
      were analyzed using the Atomic Absorption Spectrophotometer (AAS). The cadmium
      levels ranged from 0.003-0.081 mg/L for the canned and 0.006-0.071 mg/L for non
      canned beverages. About 85.71% of the canned beverages had cadmium levels that
      exceeded the maximum contaminant level (MCL) of 0.005 mg/L set by US EPA while
      82.7% non-canned beverages had cadmium levels exceeding the MCL. The mean and
      median levels of cadmium exceeded the MCL in both the canned and non-canned
      beverages. Whereas only 79.3% of the non-canned beverages showed lead levels that
      exceeded the US EPA's MCL of 0.015 mg/L, 100% of the canned beverages had lead
      levels that were greater than the MCL. The range of the lead in the canned
      beverages was 0.002-0.0073 and 0.001-0.092 mg/L for the non-canned beverages. The
      mean and median values of lead exceeded the MCL in both the canned and non-canned
      beverages. The calculated amount of lead and cadmium in three beverages were
      0.204 mg (204 microg) and 0.177 mg (177 microg), respectively. These represent
      the estimated intake of a consumer who takes three of the products selected
      randomly in a week; assuming an average volume of one liter (1 L) for each
      product. Taken together 86% and 84% of the 50 beverages (canned and non-canned)
      studied in March, 2005 in Nigeria failed to meet the US EPA criteria for
      acceptable lead and cadmium levels in consumer products.

PMID- 16442589
TI  - The effects of exogenous antioxidants on lifespan and oxidative stress resistance
      in Drosophila melanogaster.
AB  - We used the fruit fly Drosophila melanogaster to test the effects of feeding the
      superoxide dismutase (SOD) mimetic drugs Euk-8 and -134 and the mitochondria
      targeted mitoquinone (MitoQ) on lifespan and oxidative stress resistance of wild
      type and SOD-deficient flies. Our results reaffirm the findings by other workers
      that exogenous antioxidant can rescue pathology associated with compromised
      defences to oxidative stress, but fail to extend the lifespan of normal, wild
      type animals. All three drugs showed a dose-dependent increase in toxicity in
      wild type flies, an effect that was exacerbated in the presence of the redox
      cycling drug paraquat. However, important findings from this study were that in
      SOD-deficient flies, where the antioxidant drugs increased lifespan, the effects
      were sex-specific and, for either sex, the effects were also variable depending
      on (1) the stage of development from which the drugs were given, and (2) the
      magnitude of the dose. These findings place significant constraints on the role
      of oxidative stress in normal ageing.

PMID- 16442591
TI  - Calcium polysulfide remediation of hexavalent chromium contamination from
      chromite ore processing residue.
AB  - Past disposal of high-lime chromite ore processing residue (COPR) from a chemical
      works in S.E. Glasgow, UK, has led to continuing release of toxic and
      carcinogenic hexavalent chromium (Cr(VI)) to groundwaters which are highly
      contaminated with Cr(VI)O4(2-). Traditional methods of remediating Cr(VI)
      contaminated land, e.g. using ferrous sulfate and organic matter, have had
      limited success in converting Cr(VI) to less harmful and insoluble Cr(III). This
      paper describes the first application of calcium polysulfide (CaS(x)) to the
      remediation of contaminated groundwater and high-lime COPR in a series of
      laboratory experiments, which have demonstrated the effectiveness of the
      treatment in quantitatively and rapidly reducing Cr(VI) to Cr(III) over the pH
      range (8-12.5) typically found at the sites. Cr(III)-organic complexes, present
      in groundwater at one location, were also effectively precipitated upon treatment
      with CaS(x). The potential for large-scale use of CaS(x) in the remediation of
      Cr(VI) from COPR is also discussed.

PMID- 16442592
TI  - Environmental costs of mercury pollution.
AB  - Mercury (Hg) has been used for millennia in many applications, primarily in
      artisanal mining and as an electrode in the chlor-alkali industry. It is
      anthropogenically emitted as a pollutant from coal fired power plants and
      naturally emitted, primarily from volcanoes. Its unique chemical characteristics
      enable global atmospheric transport and it is deposited after various processes,
      ultimately ending up in one of its final sinks, such as incorporated into deep
      sediment or bioaccumulated, primarily in the marine environment. All forms of Hg
      have been established as toxic, and there have been no noted biological benefits
      from the metal. Throughout time, there have been notable incidents of Hg
      intoxication documented, and the negative health effects have been documented to
      those chronically or acutely exposed. Today, exposure to Hg is largely diet or
      occupationally dependent, however, many are exposed to Hg from their amalgam
      fillings. This paper puts a tentative monetary value on Hg polluted food sources
      in the Arctic, where local, significant pollution sources are limited, and
      relates this to costs for strategies avoiding Hg pollution and to remediation
      costs of contaminated sites in Sweden and Japan. The case studies are compiled to
      help policy makers and the public to evaluate whether the benefits to the global
      environment from banning Hg and limiting its initial emission outweigh the
      benefits from its continued use or lack of control of Hg emissions. The cases we
      studied are relevant for point pollution sources globally and their remediation
      costs ranged between 2,500 and 1.1 million US dollars kg(-1) Hg isolated from the
      biosphere. Therefore, regulations discontinuing mercury uses combined with
      extensive flue gas cleaning for all power plants and waste incinerators is cost
      effective.

PMID- 16442593
TI  - Randomized Phase II study comparing paclitaxel and carboplatin versus
      mitoxantrone in patients with hormone-refractory prostate cancer.
AB  - OBJECTIVES: Mitoxantrone/prednisone was the 2002 palliative reference treatment
      for hormone-refractory prostate cancer (HRPC). Paclitaxel and carboplatin has
      demonstrated antitumor activity in HRPC. The therapeutic benefit of such
      treatment was compared with that of mitoxantrone. METHODS: A randomized Phase II
      study was conducted that included 40 patients with HRPC who had not undergone
      chemotherapy. Patients in arm A received paclitaxel (175 mg/m2 every 3-week
      cycle) and carboplatin (area under the curve of 5 every 3-week cycle). Patients
      in arm B received mitoxantrone (12 mg/m2 every 3-week cycle). All the patients
      treated were receiving low-dose prednisone. The primary endpoint was the prostate
      specific antigen response. RESULTS: The prostate-specific antigen response to
      paclitaxel and carboplatin was significantly greater (40% [95% confidence
      interval 18.5% to 61.5%] versus 10% [95% confidence interval 1% to 32%], P =
      0.031) and more durable (8.6 versus 2 months, P = 0.015) than the response to
      mitoxantrone. A tendency was noted for patients with measurable disease who were
      receiving paclitaxel and carboplatin to have a somewhat greater objective
      response rate than those who received mitoxantrone (23% [95% confidence interval
      5.3% to 55%] versus no objective response, P = 0.060). The median overall
      survival was 14.5 months for the paclitaxel and carboplatin arm compared with
      11.1 months for the mitoxantrone arm. The group given paclitaxel and carboplatin
      had significantly greater rates of sensitive neuropathy (50% versus 0%, P =
      0.00026). CONCLUSIONS: The 3-week regimen of paclitaxel and carboplatin induced a
      greater and more durable prostate-specific antigen response than did mitoxantrone
      for HRPC treatment. The major additive toxicity induced was peripheral neuropathy
      due to paclitaxel. Investigations with paclitaxel and carboplatin regimens merit
      large Phase III studies.

PMID- 16442594
TI  - More favorable tumor features and progression-free survival rates in a
      longitudinal prostate cancer screening study: PSA era and threshold-specific
      effects.
AB  - OBJECTIVES: To describe the changes in pathologic outcomes and progression-free
      survival (PFS) rates after radical retropubic prostatectomy for clinically
      localized prostate cancer in men whose cancers were detected in a 12-year
      longitudinal prostate cancer screening study. METHODS: Between 1989 and 2001,
      more than 36,000 men participated in a digital rectal examination-based and
      prostate-specific antigen (PSA)-based screening program. In 1995, the PSA cutoff
      for biopsy recommendation was lowered from 4.0 ng/mL to 2.6 ng/mL, and the biopsy
      protocol was changed from four to at least six-sector biopsies. From the
      screening study, 2952 men were diagnosed with cancer and 2241 of these men
      underwent radical retropubic prostatectomy. We analyzed the differences in
      clinical and pathologic stage and PFS after surgery, according to the greater PSA
      cutoff era (1989 to 1995) and lower PSA cutoff era (1996 to 2001). RESULTS: A
      significant downward clinical and pathological stage migration was found toward
      T1c and organ-confined disease, respectively, in men whose cancer was detected in
      the lower PSA cutoff era. Furthermore, men with cancer diagnosed in the lower PSA
      cutoff era had improved PFS rates 5 and 8 years after radical retropubic
      prostatectomy (P = 0.007). These changes occurred without a significant increase
      in the proportion of unimportant tumors (organ confined, smaller than 0.5 cm3
      without a Gleason pattern of 4 or 5). CONCLUSIONS: These findings support the
      enhanced detection of favorable cancer and improved PFS rates with lower PSA
      cutoffs and more intensive biopsy regimens, although the follow-up and lead-time
      and length-time biases, as well as improvements in surgical technique, might also
      have affected these results.

PMID- 16442595
TI  - Prostate-specific antigen test in diagnostic evaluation of chronic
      prostatitis/chronic pelvic pain syndrome.
AB  - OBJECTIVES: To determine whether prostate-specific antigen (PSA), the percent
      free PSA, or free PSA isoforms may be used as diagnostic markers for chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS; National Institutes of Health
      category IIIa and IIIb). METHODS: We evaluated 421 patients enrolled in the
      Chronic Prostatitis Cohort Study and 112 age-matched controls. Subjects were
      stratified by the number of white blood cells (WBCs) in their expressed prostatic
      secretions and pain as determined by the National Institutes of Health Chronic
      Prostatitis Symptom Index. RESULTS: Total PSA, free PSA, and [-2]proPSA ([
      2]pPSA) were significantly elevated in those with CP/CPPS compared with controls
      (mean PSA 1.97 ng/mL versus 1.72 ng/mL, P = 0.03; mean free PSA 0.76 ng/mL versus
      0.70 ng/mL, P = 0.01; and [-2]pPSA 2.38 ng/mL versus 1.80 ng/mL, P = 0.04). The
      percent free PSA was not significantly different between the patients and
      controls. For those with CP/CPPS, the percent free PSA was significantly lower as
      the WBC count rose in the expressed prostatic secretions (0 WBCs = 43.29 versus
      more than 25 WBCs = 26.52; P < .0001). A PSA level of 4.0 ng/mL or greater was
      found in 10% of patients and 7% of controls (P = 0.03). CONCLUSIONS: Men with
      elevated PSA values and CP/CPPS should be treated as one would any other patient
      screened for prostate cancer with an elevated PSA level. Although PSA, free PSA,
      and [-2]pPSA were slightly elevated in men with CP/CPPS, the low sensitivity and
      specificity do not warrant using them as biomarkers for CP/CPPS.

PMID- 16442596
TI  - Changes in quality of life in first year after radical prostatectomy by
      retropubic, laparoscopic, and perineal approach: Multi-institutional longitudinal
      study in Japan.
AB  - OBJECTIVES: To investigate the health-related quality of life of patients who
      underwent radical prostatectomy performed using retropubic, laparoscopic, and
      perineal approaches. METHODS: A total of 218 men who underwent retropubic
      prostatectomy, 65 who underwent laparoscopic prostatectomy, and 66 who underwent
      perineal prostatectomy were enrolled in our survey. A baseline interview was
      conducted before treatment. Follow-up interviews were conducted in person at
      scheduled study visits 1, 3, 6, and 12 months after surgery. We measured two
      validated questionnaires that assessed the general and disease-specific health
      related quality of life. RESULTS: The retropubic group reported substantial
      deterioration in physical limitations, emotional limitations, social function,
      and bodily pain at 1 month. The perineal group reported less bodily pain just
      after surgery than the retropubic and laparoscopic groups. After 6 months,
      however, no significant differences were found among the three groups.
      Postoperative urinary function remained substantially lower than the baseline
      level in every treatment group. Each approach with a nerve-sparing procedure
      showed a similar recovery profile of urinary function postoperatively. The
      perineal group reported no significant difference in bowel function compared with
      the other two groups. All of the groups continued to have decrements in sexual
      function. CONCLUSIONS: The results of this study have demonstrated that
      retropubic, laparoscopic, and perineal prostatectomy have differences in the
      recovery of general and disease-specific quality of life in the early
      postoperative period. When performed by an experienced surgeon, the retropubic,
      laparoscopic, and perineal approaches appear to be equivalent in terms of health
      related quality of life.

PMID- 16442597
TI  - Baseline prostate-specific antigen compared with median prostate-specific antigen
      for age group as predictor of prostate cancer risk in men younger than 60 years
      old.
AB  - OBJECTIVES: Limited data are available concerning the extent to which the initial
      prostate-specific antigen (PSA) measurement in men younger than age 60 predicts
      for the risk of prostate cancer (CaP) and how this compares to other known risk
      factors. METHODS: From 1991 to 2001, 13,943 men younger than 60 years old
      participated in a CaP screening study. Men aged 40 to 49 years were eligible for
      the study if they had a positive family history or African-American heritage, and
      men older than 50 years were screened without respect to risk factors. The CaP
      detection rate, PSA velocity, pathologic features, and treatment outcomes were
      evaluated as a function of the baseline PSA level. RESULTS: The median PSA level
      was 0.7 ng/mL for men aged 40 to 49 years and 0.9 ng/mL for men aged 50 to 59. A
      baseline PSA level between the median and 2.5 ng/mL was associated with a 14.6
      fold and 7.6-fold increased risk of CaP in men aged 40 to 49 and 50 to 59 years,
      respectively. A greater baseline PSA value was also associated with a
      significantly greater PSA velocity, more aggressive tumor features, a greater
      biochemical progression rate, and a trend toward a greater cancer-specific
      mortality rate. CONCLUSIONS: In men younger than 60, a baseline PSA value between
      the age-specific median and 2.5 ng/mL was a significant predictor of later CaP
      and was associated with a significantly greater PSA velocity. A young man's
      baseline PSA value was a stronger predictor of CaP than family history, race, or
      suspicious digital rectal examination findings. A greater baseline PSA level was
      associated with significantly more adverse pathologic features and biochemical
      progression.

PMID- 16442599
TI  - Racial disparities in resource utilization for cystectomy.
AB  - OBJECTIVES: To examine the association of race with mortality and resource use
      among patients requiring cystectomy for bladder cancer, given the known racial
      differences with regard to bladder cancer incidence and survival. METHODS: Using
      the Nationwide Inpatient Sample (a nationally representative data set), 22,088
      patients who underwent cystectomy for bladder cancer from 1988 to 2000 were
      identified using the International Classification of Disease, Ninth Revision,
      codes. The outcomes included in-hospital mortality, length of stay (LOS), and
      discharge status. Multivariable models were developed to perform risk-adjusted
      analyses and identify factors associated with these outcomes. RESULTS: The
      overall mortality rate after cystectomy was 2.9%. Unadjusted analyses revealed
      significant racial differences with respect to in-hospital mortality, LOS, and
      discharge disposition. Whites had a mortality rate of 2.8% compared with 4.2% for
      blacks and 3.9% for Hispanics (P = 0.006). Whites had a prolonged LOS 24.9% of
      the time compared with 38.2% for blacks and 24.6% for Hispanics (P < 0.001). The
      rate at which whites were discharged to subacute care facilities was 9.9%
      compared with 11.2% for black patients and 7.7% for Hispanics (P < 0.001). After
      adjusting for confounding factors, blacks were more likely to experience in
      hospital mortality and prolonged LOS (odds ratios 1.66 and 2.10, respectively)
      compared with whites, although no significant differences were observed for
      Hispanics. No significant racial differences were noted for discharge status
      after risk adjustment. CONCLUSIONS: Black patients undergoing cystectomy for
      bladder cancer had greater mortality and greater LOS than did white patients.
      Additional study using detailed clinical data is necessary to identify the
      underlying causes of these differences.

PMID- 16442598
TI  - Effect of homeodomain protein NKX3.1 R52C polymorphism on prostate gland size.
AB  - OBJECTIVES: To determine the association between prostatic enlargement and a
      cytosine for thymine genetic polymorphism at nucleotide 154 (C154T) of the NKX3.1
      prostate homeobox gene. The polymorphism, found in 10% of the population, affects
      the NKX3.l protein by replacing a cysteine for arginine at amino acid 52 and
      alters protein phosphorylation and DNA binding. METHODS: A study group of men
      without prostate cancer from the Prostate, Lung, Colorectal, and Ovarian Cancer
      Screening Trial was identified who had had at least three annual serial digital
      rectal examinations by a single examiner. The cohort of 772 men consisted of the
      lowest and highest tertiles of the entire study group as defined by two
      dimensional measurements at digital rectal examination. The TaqMan allelic
      discrimination assay was used to genotype NKX3.1 for the nucleotide 154
      polymorphism. RESULTS: The men in the lower tertile (n = 413) had a mean age of
      60.8 years, mean prostate-specific antigen level of 1.2 ng/mL, and mean prostate
      volume of 37.9 +/- 4.5 cm3. The men in the upper tertile (n = 359) had a mean age
      of 61.6 years, mean prostate-specific antigen level of 2.1 ng/mL, and mean
      prostate volume of 61 +/- 6.3 cm3. The men in the upper tertile had a greater
      likelihood of having a clinical history of benign prostatic hyperplasia and more
      frequent nocturia. The presence of one or two polymorphic NKX3.1 alleles
      conferred a risk of 1.6 (95% confidence interval 1.0 to 2.6) for an enlarged
      prostate (highest tertile). CONCLUSIONS: The NKX3.1 nucleotide 154 C/T or T/T
      genotype increases the relative odds for prostatic enlargement. The group with
      prostatic enlargement also had increased clinical benign prostatic hyperplasia
      and nocturia.

PMID- 16442600
TI  - Perineocele: symptom complex, description of anatomic defect, and surgical
      technique for repair.
AB  - OBJECTIVES: To describe the patient characteristics, physical examination and
      magnetic resonance imaging findings, and method of surgical repair of
      perineocele. A perineocele is a rare condition of an isolated central defect and
      herniation of the posterior perineum in patients without diffuse vaginal
      prolapse. METHODS: The evaluation consisted of history and physical examination
      and magnetic resonance imaging. With the patient in the dorsal lithotomy
      position, an inverted Y incision was made from the posterior vagina to the
      posterior rectum. The transverse perineal musculature, superficial perineal
      membrane, and external anal sphincter were approximated. The perineal distance
      from the posterior fourchette to the anus was measured preoperatively and
      postoperatively. Symptom and anatomic assessments were done at each postoperative
      visit. RESULTS: A total of 6 patients were treated, with a mean follow-up of 9.5
      months. The symptoms at presentation consisted of perineal pressure, severe
      constipation, and the need for manual perineal reduction for defecation. The
      physical findings included a lack of vaginal prolapse, convexity of the perineum,
      and an increase in the distance from the posterior fourchette to the rectum.
      Dynamic magnetic resonance imaging showed no anomaly of the vaginal wall.
      Preoperatively, the average perineal distance was 11.2 cm and postoperatively it
      was 4 cm. The perineocele was successfully repaired in all patients. All but 1
      patient had significant relief of constipation. CONCLUSIONS: Posterior levator
      defects can result in perineal hernia with perineal body attenuation, separation
      of the transverse perineal and anal sphincter musculature, and development of a
      perineocele. The relief of symptoms and correction of the anatomic defect can be
      achieved by reapproximation of these structures.

PMID- 16442602
TI  - Patient opinion of urologists' reimbursement.
AB  - OBJECTIVES: To determine patient assumptions and opinions of the billing and
      reimbursement process in an urban urologic practice. Healthcare policy and
      physician reimbursement has been discussed in political and economic forums;
      however, few studies exist that reflect a patient's perspective of reimbursement
      issues. METHODS: An anonymous, voluntary 11-question survey was given to 825
      patients during a 10-week interval. The instrument measured patient perceptions
      on the amounts (in percentages) that would, and should, be covered by insurance
      carriers and collected by their urologist. It also measured the time frames
      perceived for these events to occur. Our aim was to evaluate their knowledge of
      office urologic reimbursement. RESULTS: Overall, 532 patients (75%) surveyed
      believed their insurance would cover 80% to 100% of their bill. A total of 309
      patients (49%) thought their urologist would receive 80% to 100% of the bill, and
      383 (60%) thought they should receive that level of compensation (P < 0.0001).
      Respondents with prior surgical contact thought their urologist would (P = 0.004)
      and should (P = 0.01) be reimbursed at a greater level than those without prior
      surgical contact. When asked about the time to reimbursement, 340 (73%) thought
      their doctor would be paid within 6 weeks compared with 453 (95%) who thought
      their urologist should be paid within that time (P < 0.0001). CONCLUSIONS: The
      survey responses demonstrated patients' convictions that their urologists should
      be reimbursed in a timely manner. Additional studies examining both patient and
      healthcare provider perspectives are needed to better educate both of these
      groups on the medical billing and reimbursement process.

PMID- 16442601
TI  - National utilization trends of partial nephrectomy for renal cell carcinoma: a
      case of underutilization?
AB  - OBJECTIVES: Partial nephrectomy is perceived to be more technically demanding
      than radical nephrectomy; concurrently, the increasing incidence of small renal
      tumors has suggested a greater role for nephron-sparing techniques. From a
      quality-of-care perspective, the underuse of partial nephrectomy may represent
      suboptimal delivery of healthcare. METHODS: A total of 66,621 subjects undergoing
      radical and partial nephrectomy for kidney cancer between 1988 and 2002 were
      identified from the Nationwide Inpatient Sample, a nationally representative data
      set of hospital discharges. Adjusted models were developed to identify clinical
      factors and structural measures independently associated with the use of partial
      nephrectomy. RESULTS: Overall, 7.5% of patients treated underwent partial
      nephrectomy. The utilization rates for partial nephrectomy ranged from 0.21 cases
      per 100,000 U.S. residents in 1988 to 1.6 cases per 100,000 U.S. residents in
      2002. The percentage of patients with renal cell carcinoma treated with partial
      nephrectomy has increased more than threefold during the study interval (3.7% in
      1988 to 1990 compared with 12.3% in 2000 to 2002, P <0.0001 for trend). Patients
      treated at urban (odds ratio 1.1), teaching (odds ratio 1.3), and high
      nephrectomy volume (odds ratio 2.5) hospitals were more likely to undergo partial
      nephrectomy (each, P <0.01). CONCLUSIONS: The national use of partial nephrectomy
      has increased but remains lower than expected in certain settings, suggesting
      underuse or selective referral. Subjects with kidney cancer are more likely to be
      treated with partial nephrectomy at teaching institutions with high surgical
      volumes. The practice patterns of physicians at institutions more commonly using
      partial nephrectomy may reflect a better quality of care, although additional
      work in delineating the disparate utilization rates is warranted.

PMID- 16442603
TI  - Symptoms and cystoscopic findings in patients with untreated interstitial
      cystitis.
AB  - OBJECTIVES: To examine the relationships between symptoms and cystoscopic
      findings in women newly diagnosed with interstitial cystitis who had not
      previously received treatment. METHODS: Twelve newly diagnosed and not previously
      treated women with interstitial cystitis completed a bladder symptom
      questionnaire the day before undergoing cystoscopy, hydrodistension, and biopsy.
      The daily voiding frequency was reported. Cystoscopic findings were converted to
      a numerical scale, and the data were analyzed using Pearson correlations.
      RESULTS: Pain symptoms had consistent positive correlations with the cystoscopic
      findings. An increase in pain with bladder filling was associated with
      inflammation (P = 0.011), ulceration, and smaller bladder capacity. Pain relief
      after voiding correlated with smaller bladder capacity (P = 0.019), hematuria,
      and total cystoscopic score. Pain intensity in the urethra was related to
      ulceration and hematuria, and pain in the lower abdomen was related to a smaller
      bladder capacity (P = 0.047), glomerulations, and a larger total cystoscopic
      score. Daytime frequency correlated negatively with most cystoscopic findings,
      and nocturnal frequency had a positive relationship with most cystoscopic
      findings and was significantly associated with a smaller bladder capacity (P =
      0.010). Urgency showed no strong associations with any cystoscopic findings.
      CONCLUSIONS: In patients with untreated interstitial cystitis, a strong
      correlation between pain and cystoscopic findings was observed. The differences
      between our results and those of previous studies that found no relationship
      between symptom reports and cystoscopic findings suggest possible effects of
      treatment on pain perception and therapeutic influence on cystoscopic findings.

PMID- 16442604
TI  - Management of postoperatively detected iatrogenic lower ureteral injury: should
      ureteroureterostomy really be abandoned?
AB  - OBJECTIVES: To reevaluate the role of ureteroureterostomy in the management of
      postoperatively detected iatrogenic lower ureteral injury. Despite the advantages
      of preserving the integrity of bladder and the natural antireflux mechanism, open
      end-to-end ureteroureterostomy is rarely performed today for treatment of lower
      ureteral injury diagnosed postoperatively. METHODS: A retrospective analysis was
      performed of 9 patients (all women, mean age 49.2 years) who had received end-to
      end ureteroureterostomy from 1998 to 2002 for postoperatively detected iatrogenic
      lower ureteral injuries sustained during gynecologic or general surgery. RESULTS:
      All patients had the intact distal ureteral stumps identified by retrograde
      pyelography before undergoing ureteroureterostomy. Open end-to-end
      ureteroureterostomies with double-J catheter stenting were performed as soon as
      the diagnosis had been made (interval from injury to repair 10 days to 21 weeks).
      The mean length of the eventually resected segments of the injured lower ureter
      was 2.7 cm, and the mean distance between the distal margin of the injured
      ureteral segment and the ureterovesical junction measured intraoperatively was
      2.9 cm. Renal mobilization was required in 1 patient. In 1 patient who had a
      bilateral ureteral injury, ureteroureterostomy was performed on only one side,
      with a psoas hitch on the contralateral side. In all cases, the initially
      observed hydronephrosis and fistula disappeared after surgery, and no
      complications were observed during a mean follow-up of 33.7 months (range 6 to
      55). CONCLUSIONS: Ureteroureterostomy may still be considered a realistic
      treatment option in the case of postoperatively detected iatrogenic lower
      ureteral injuries with distal ureteral stumps preserved and identified on
      retrograde pyelography.

PMID- 16442605
TI  - Therapeutic effects of suburothelial injection of botulinum a toxin for
      neurogenic detrusor overactivity due to chronic cerebrovascular accident and
      spinal cord lesions.
AB  - OBJECTIVES: To investigate the therapeutic effects of suburothelial botulinum A
      toxin for patients with chronic cerebrovascular accident (CVA) and spinal cord
      lesions. Suburothelial injection of botulinum A toxin can effectively inhibit the
      occurrence of neurogenic detrusor overactivity. METHODS: Twenty-four patients
      with neurogenic detrusor overactivity refractory to anticholinergics were
      enrolled and treated with 200 U of botulinum A toxin injected into the
      suburothelial space. The clinical effects on the lower urinary tract symptoms and
      urodynamic parameters were assessed. RESULTS: Of the 24 patients enrolled in the
      study, 12 had CVA and 12 had suprasacral cord lesions (SCLs). After treatment,
      the volume of the first involuntary detrusor contraction and bladder capacity
      increased twofold and the postvoid residual volume fourfold for both patient
      groups after 1 month, decreasing slightly at 3 months. The detrusor pressure for
      the SCL group decreased significantly after treatment (39.1 +/- 16.6 versus 21.2
      +/- 14.1, P = 0.002) relative to the CVA patients. Complete continence and
      improvement of incontinence grade were achieved in 1 (8.3%) and 5 (41.7%)
      patients with CVA and in 4 (33.3%) and 7 (58.3%) patients with SCLs. However,
      patients in both groups experienced an increase in voiding difficulty after
      treatment. The therapeutic effect declined gradually after 3 months, and all
      patients had experienced symptom relapse by 6 months. CONCLUSIONS: Suburothelial
      botulinum A toxin at a dose of 200 U increased bladder capacity and improved the
      incontinence grade in 91.6% of the patients with SCL, but this was achieved for
      only 50% of the patients with CVA.

PMID- 16442606
TI  - Vasodilatory factors in treatment of older men with symptomatic benign prostatic
      hyperplasia.

PMID- 16442607
TI  - Pelvic radiation necrosis and osteomyelitis following chemoradiation for advanced
      stage vulvar and cervical carcinoma.
AB  - BACKGROUND: The treatment regimen indicated for most advanced stage vulvar,
      vaginal, and cervical cancer usually involves adjuvant chemoradiation therapy.
      Although the risk of complications is low, there have been reported cases of
      radiation necrosis and osteomyelitis following treatment for vulvar, vaginal, and
      cervical cancer. CASES: We present a vulvar cancer patient and a cervical cancer
      patient, both of whom were treated with radical surgery and postoperative
      chemoradiation. Following therapy, they were afflicted with pelvic radiation
      necrosis and osteomyelitis. The patients underwent surgery to resect the necrotic
      bone tissue and long-term antibiotic therapy to treat their osteomyelitis. They
      have since recovered and are followed closely by their gynecologic oncology and
      infectious disease physicians. CONCLUSION: The radiotherapy utilized to treat
      advanced stage gynecologic cancer can cause intestinal, vaginal, and urologic
      complications from micro-vascular damage to the organs. Pelvic bone osteonecrosis
      is a rare but disabling complication of pelvic radiation. Fortunately, with
      aggressive therapy, these patients may do well clinically.

PMID- 16442608
TI  - Daily patterns of ethanol drinking in peri-adolescent and adult alcohol
      preferring (P) rats.
AB  - Alcohol abuse among adolescents continues to be a major health problem for our
      society. Our laboratory has used the peri-adolescent alcohol-preferring, P, rat
      as an animal model of adolescent alcohol abuse. Even though peri-adolescent P
      rats consume more alcohol (g/kg/day) than their adult counterparts, it is
      uncertain whether their drinking is sufficiently aggregated to result in
      measurable blood ethanol concentrations (BECs). The objectives of this study were
      to examine daily alcohol drinking patterns of adolescent and adult, male and
      female P rats, and to determine whether alcohol drinking episodes were
      sufficiently aggregated to result in meaningful BECs. Male and female P rats were
      given 30 days of 24 h free-choice access to alcohol (15%, v/v) and water, with ad
      lib access to food, starting at the beginning of adolescence (PND 30) or
      adulthood (PND 90). Water and alcohol drinking patterns were monitored 22 h/day
      with a "lickometer" set-up. The results indicated that (a) peri-adolescent P rats
      consumed more water and total fluids than adult P rats, (b) female P rats
      consumed more water and total fluids than male P rats, (c) there were differences
      in alcohol, and water, licking patterns between peri-adolescent and adult and
      female and male P rats, (d) individual licking patterns revealed that alcohol was
      consumed in bouts often exceeding the amount required to self-administer 1 g/kg
      of alcohol, and (e) BECs at the end of the dark cycle, on the 30th day of alcohol
      access, averaged 50 mg%, with alcohol intakes during the last 1 to 2 h averaging
      1.2 g/kg. Overall, these findings indicate that alcohol drinking patterns differ
      across the age and sex of P rats. This suggests that the effectiveness of
      treatments for reducing excessive alcohol intake may vary depending upon the age
      and/or sex of the subjects being tested.

PMID- 16442609
TI  - Ovariectomy during the luteal phase influences secretion of prolactin, growth
      hormone, and insulin-like growth factor-I in the bitch.
AB  - A decline in circulating progesterone concentration plays an important role in
      the ethiopathogenesis of pseudopregnancy in the bitch. Because growth hormone
      (GH) and prolactin (PRL) are essential for normal mammogenesis and the secretion
      of these hormones is influenced by changes in the circulating progesterone
      concentration, the purpose of this study was to investigate the effects of mid
      luteal phase ovariectomy on the 6-h pulsatile plasma profiles of GH and PRL and
      the basal plasma concentrations of GH, PRL, and insulin-like growth factor-I (IGF
      I) in six beagle bitches. Ovariectomy was followed by only mild or covert signs
      of pseudopregnancy. The sharp decrease of the plasma progesterone concentration
      was accompanied by decreased basal plasma concentrations of GH and IGF-I and a
      rise in basal plasma PRL concentration. GH and PRL were secreted in a pulsatile
      fashion both prior to and after ovariectomy. The mean basal plasma GH
      concentration was significantly higher before ovariectomy than on days 1 and 7
      after ovariectomy. The mean area under the curve above the zero level (AUC(0))
      for GH was significantly higher before than at 7 days after ovariectomy. The mean
      area under the curve above basal level (AUC(b)) and the frequency of GH pulses at
      7 days after ovariectomy were significantly higher than before and 1 day after
      ovariectomy. Both the mean basal plasma PRL concentration and the mean AUC(0) for
      PRL increased after ovariectomy. In conclusion, ovariectomy of bitches in the mid
      luteal phase stops progesterone-induced GH release from the mammary gland, as
      evidenced by the lowering of basal plasma GH levels, the recurrence of GH
      pulsatility, and the lowering of circulating IGF-I levels. The sudden lowering of
      plasma progesterone concentration is probably a primary cause of a prolonged
      increase in PRL secretion. These observations underscore the importance of
      similar, albeit less abrupt, hormonal changes in the cyclical physiological
      alterations in the mammary gland and in the development of pseudopregnancy.

PMID- 16442611
TI  - A screening procedure for the solubilization of chloroplast membrane proteins
      from the marine green macroalga Ulva lactuca using RP-HPLC-MALDI-MS.
AB  - A protocol for purification and analysis of chloroplast membrane proteins in the
      green macroalga Ulva lactuca has been developed, including reversed phase high
      performance liquid chromatography (RP-HPLC) and matrix assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Five
      different solvents were evaluated for extraction of membrane proteins by three
      methods. The highest protein yield was achieved when proteins were extracted
      directly from the chloroplasts using the solvent hexafluoroisopropanol. A range
      of proteins of increasing hydrophobicity was separated by HPLC. Analysis of both
      HPLC fractions and non-separated samples by MALDI-TOF-MS revealed proteins with
      molecular weights spanning between 1 and 376 kDa.

PMID- 16442610
TI  - Preparation of semi-interpenetrating polymer networks composed of chitosan and
      poloxamer.
AB  - Through semi-interpenetration of polymer networks with poloxamer, mechanical
      properties of chitosan (CS) sponge were increased for wound dressing application.
      Synthesis of poloxamer macromer was confirmed by proton nuclear magnetic
      resonance (1H NMR) spectra. Possible interactions between CS and poloxamer in
      semi-interpenetrating polymer networks (SIPNs), and changes in crystalline
      structures of both polymers were evaluated by Fourier-transform infrared
      spectroscopy (FTIR) and X-ray diffraction (XRD), respectively. Swelling behavior,
      thermal analysis, mechanical properties, and morphology of SIPNs were studied by
      thermal gravimetric analysis, differential scanning calorimetry (DSC),
      compressive modulus measurement, and scanning electron microscopy (SEM),
      respectively. Preparation of poloxamer macromer, and intermolecular hydrogen
      bonding between CS and poloxamer were confirmed by NMR and FTIR, respectively.
      Melting temperature of poloxamer in SIPNs decreased due to prevention of
      crystallization by incorporation of CS. Formation of SIPNs with poloxamer and
      increasing poloxamer content in CS/poloxamer SIPNs increased mechanical strength
      of CS sponge compared with CS/poloxamer blend. Formation of SIPNs with poloxamer
      remarkably increased water content of CS due to hydrophilicity of CS and
      poloxamer. These results suggest CS/poloxamer sponges prepared by SIPNs method
      have good possibility for wound dressing application owing to rapid water
      adsorption, high mechanical strength, and interconnected cross-sectional
      morphology of SIPNs.

PMID- 16442612
TI  - Expression, purification and refolding of the phosphatase domain of protein
      phosphatase 1 (Ppt1) from Saccharomyces cerevisiae.
AB  - Here we report the recombinant expression of the catalytically active phosphatase
      domain of the Saccharomyces cerevisiae protein phosphatase 1 (Ppt1) in E. coli.
      Ppt1 consists of two domains: a 20 kDa TPR (tetratricopeptide repeat) domain,
      which mediates protein-protein interactions and directs Ppt1 to potential
      substrate proteins, e.g. the molecular chaperone Hsp90. The second, a 40 kDa
      phosphatase domain, exhibits catalytic activity and dephosphorylates
      phosphorylated serine/threonine residues of respective substrate proteins. The
      Ppt1 phosphatase domain was cloned and expressed in E. coli in unsoluble
      inclusion bodies. After isolating these, the aggregates were denatured with
      guanidinium hydrochloride and soluble protein was purified using affinity
      chromatography. Optimal renaturation conditions led to large amounts of the
      refolded phosphatase domain in high purity. Interestingly, further enzymatic
      studies revealed that the domain is not only correctly folded, but also shows
      higher catalytic activity compared to the full length protein.

PMID- 16442613
TI  - pH- and temperature-responsive hydrogels from crosslinked triblock copolymers
      prepared via consecutive atom transfer radical polymerizations.
AB  - Well-defined poly((2-dimethyl amino)ethyl methacrylate-co-2-hydroxyethyl
      methacrylate)-b-poly(N-isopropylacrylamide)-b-poly((2-dimethyl amino)ethyl
      methacrylate-co-2-hydroxyethyl methacrylate), or P(DMAEMA-co-HEMA)-b-P(NIPAAm)-b
      P(DMAEMA-co-HEMA), triblock copolymers were synthesized by consecutive atom
      transfer radical polymerizations (ATRPs), using ethylene glycol di-2
      bromoisobutyrate (Br-EG-Br) as the starting ATRP initiator. The hydroxyl groups
      of the incorporated HEMA units were used as crosslinking sites for the
      preparation of smart hydrogels. The so-prepared hydrogels exhibited both
      temperature- and pH-sensitive behavior derived, respectively, and independently,
      from the P(NIPAAm) blocks and P(DMAEMA) units, in the crosslinked matrices. The
      hydrogels exhibited a lower critical solution temperature (LCST) of 31-32 degrees
      C in aqueous media of pH 1-7, not unlike that of the P(NIPAAm) homopolymer. The
      swelling ratios and swelling/deswelling kinetics of the hydrogels depended
      strongly on pH and temperature of the medium. The copolymers were characterized
      by gel-permeation chromatography, X-ray photoelectron spectroscopy (XPS), Fourier
      transform infrared (FTIR) spectroscopy, and (1)H nuclear magnetic resonance ((1)H
      NMR) spectroscopy. The resultant stimuli-responsive hydrogels were characterized
      by differential scanning calorimetry (DSC). These stimuli-responsive hydrogels
      will have potential applications in biomedical areas, such as tissue engineering
      and drug delivery.

PMID- 16442614
TI  - Nutritional modulation of adolescent pregnancy outcome -- a review.
AB  - The risks of miscarriage, prematurity and low birth weight are particularly acute
      in adolescent girls who are still growing at the time of conception. The role of
      maternal nutrition in mediating pregnancy outcome in this vulnerable group has
      been examined in sheep models. When singleton bearing adolescent dams are
      overnourished to promote rapid maternal growth throughout pregnancy, growth of
      both the placenta and fetus is impaired, and birth occurs prematurely relative to
      control adolescents of equivalent age. Studies at mid-gestation, prior to
      alterations in placental mass, suggest that reduced proliferation of the fetal
      trophectoderm, impaired angiogenesis, and attenuated uteroplacental blood flows
      are early defects in placental development. By late pregnancy, relative placental
      mass is reduced by 45% but uteroplacental metabolism and placental glucose
      transfer capacity remain normal when expressed on a placental weight specific
      basis. The asymmetrically growth-restricted fetuses are hypoxic, hypoglycemic and
      have reduced insulin and IGF-1 concentrations. Absolute umbilical nutrient
      uptakes are attenuated but fetal utilisation of glucose, oxygen and amino acids
      remains normal on a fetal weight basis. This suggests altered sensitivities to
      metabolic signals and may have implications for subsequent metabolic health. At
      the other end of the nutritional spectrum, many girls who become pregnant have
      inadequate or marginal nutritional status during pregnancy. This situation is
      replicated in a second model whereby dams are prevented from growing during
      pregnancy by relatively underfeeding. Limiting maternal intake in this way
      gradually depletes maternal body reserves leading to a lower transplacental
      glucose gradient and a modest slowing of fetal growth in late pregnancy. These
      changes appear to be independent of alterations in placental growth per se. Thus,
      while the underlying mechanisms differ, maternal intake at both ends of the
      nutritional spectrum is a powerful determinant of fetal growth in pregnant
      adolescents.

PMID- 16442615
TI  - IFPA 2005 Award in Placentology Lecture. Human placental transport in altered
      fetal growth: does the placenta function as a nutrient sensor? -- a review.
AB  - Intrauterine growth restriction is associated with a range of alterations in
      placental transport functions: the activity of a number of transporters is
      reduced (Systems A, L and Tau, transporters for cationic amino acids, the sodium
      proton exchanger and the sodium pump), placental glucose transporter activity and
      expression are unchanged whereas the activity of the calcium pump is increased.
      In contrast, accelerated fetal growth in association to diabetes is characterized
      by increased activity of placental Systems A and L and glucose transporters.
      Evidence suggests that these placental transport alterations are the result of
      specific regulation and that they, at least in part, contribute to the
      development of pathological fetal growth rather than representing a consequence
      to altered fetal growth. One interpretation of this data is that the placenta
      functions as a nutrient sensor, altering placental transport functions according
      to the ability of the maternal supply line to provide nutrients. Placental
      transporters are subjected to regulation by hormones. Insulin up-regulates
      several key placental transporters and maternal insulin may represent a "good
      nutrition" signal to increase placental nutrient transfer and the growth of the
      fetus. Preliminary evidence suggests that placental mammalian target of
      rapamycin, a protein kinase regulating protein translation and transcription in
      response to nutrient stimuli, may be involved in placental nutrient sensing.

PMID- 16442616
TI  - Differential distribution of CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in
      decidua and maternal blood during human pregnancy.
AB  - During pregnancy several maternal and fetal mechanisms are established to prevent
      a destructive immune response against the allogeneic fetus. Despite these
      mechanisms, fetus specific T-cells persist throughout gestation but little is
      known about the regulation of these T-cells. Recently, CD4(+)CD25(+) regulatory T
      cells have been identified in human decidua. Human decidua forms the maternal
      part of the fetal-maternal interface and is subdivided in two distinct regions:
      the decidua (d.) basalis and the decidua (d.) parietalis. The aim of this study
      was to determine the distribution of specific T-cell subsets in d. basalis and d.
      parietalis in early and term pregnancy, with a special emphasis on the presence
      of CD4(+)CD25(bright) (regulatory) T-cells and CD8(+)CD28(-) (suppressor) T
      cells. In addition, we compared phenotypic characteristics of decidua derived T
      cell subsets with maternal peripheral blood (mPBL) T-cells and T-cells from non
      pregnant controls. We identified significantly higher percentages of
      CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in decidua compared to peripheral
      blood suggesting an important role for these T-cell subsets locally at the fetal
      maternal interface. The major differences in T-cell subset distribution and the
      presence of additional phenotypic differences between T-cells in d. basalis, d.
      parietalis and mPBL may reflect specific immunomodulatory functions of these T
      cell subsets at these different sites during pregnancy.

PMID- 16442617
TI  - A role for voltage gated T-type calcium channels in mediating "capacitative"
      calcium entry?
AB  - Calcium entry through plasma membrane calcium channels is one of the most
      important cell signaling mechanism involved in such diverse functions as
      secretion, contraction and cell growth by regulating gene expression,
      proliferation and apoptosis. The identity of plasma membrane calcium channels,
      the main regulators of calcium entry, involved in cell proliferation has been
      thus extensively sought. Among these, a calcium entry pathway called capacitative
      calcium entry (CCE), activated by calcium store depletion, is particularly
      important in non-excitable cells. Though this capacitative calcium entry is
      generally supposed to occur through TRP channels there is some evidence that
      voltage-dependent T-type calcium channels may contribute to calcium entry after
      store depletion. Here we show that though mibefradil, a T-type calcium channel
      blocker, is able to reduce capacitative calcium entry induced by either
      thapsigargin or ATP, this was not mimicked by any other T-type calcium channel
      inhibitors even in cells overexpressing alpha(1H) T-type calcium channels,
      leading us to conclude that T-type calcium channels are not responsible for the
      capacitative calcium entry observed in different cancer cell lines. On the
      contrary, we show that the action of mibefradil on capacitative calcium entry is
      due to an action on store-operated calcium channels.

PMID- 16442618
TI  - Protein kinase inhibitor peptide (PKI): a family of endogenous neuropeptides that
      modulate neuronal cAMP-dependent protein kinase function.
AB  - Signal transduction cascades involving cAMP-dependent protein kinase are highly
      conserved among a wide variety of organisms. Given the universal nature of this
      enzyme it is not surprising that cAMP-dependent protein kinase plays a critical
      role in numerous cellular processes. This is particularly evident in the nervous
      system where cAMP-dependent protein kinase is involved in neurotransmitter
      release, gene transcription, and synaptic plasticity. Protein kinase inhibitor
      peptide (PKI) is an endogenous thermostable peptide that modulates cAMP-dependent
      protein kinase function. PKI contains two distinct functional domains within its
      amino acid sequence that allow it to: (1) potently and specifically inhibit the
      activity of the free catalytic subunit of cAMP-dependent protein kinase and (2)
      export the free catalytic subunit of cAMP-dependent protein kinase from the
      nucleus. Three distinct PKI isoforms (PKIalpha, PKIbeta, PKIgamma) have been
      identified and each isoform is expressed in the brain. PKI modulates neuronal
      synaptic activity, while PKI also is involved in morphogenesis and symmetrical
      left-right axis formation. In addition, PKI also plays a role in regulating gene
      expression induced by cAMP-dependent protein kinase. Future studies should
      identify novel physiological functions for endogenous PKI both in the nervous
      system and throughout the body. Most interesting will be the determination
      whether functional differences exist between individual PKI isoforms which is an
      intriguing possibility since these isoforms exhibit: (1) cell-type specific
      tissue expression patterns, (2) different potencies for the inhibition of cAMP
      dependent protein kinase activity, and (3) expression patterns that are
      hormonally, developmentally and cell-cycle regulated. Finally, synthetic peptide
      analogs of endogenous PKI will continue to be invaluable tools that are used to
      elucidate the role of cAMP-dependent protein kinase in a variety of cellular
      processes throughout the nervous system and the rest of the body.

PMID- 16442619
TI  - Absence of the JAK2 mutation V617F in CD34+ hematopoietic stem and progenitor
      cells from patients with BCR-ABL-positive CML in chronic phase and blast crisis.
AB  - In this study, we examined highly enriched CD34+ cells from patients with BCR-ABL
      positve CML in chronic phase or blast crisis for the JAK2 V617F activation
      mutation by sequencing. The cells examined did not bear the mutation irrespective
      of the disease stage. This finding suggests that the previously described
      increase of expression and kinase activity of JAK2 in CML cells does not result
      from the JAK2 V617F activation mutation and that transformation into blast crisis
      is not associated with the occurrence of this mutation.

PMID- 16442621
TI  - A mutational analysis of the ColE1-encoded cell cycle regulator Rcd confirms its
      role in plasmid stability.
AB  - Multimers of multicopy plasmids cause instability. They arise by homologous
      recombination and accumulate by over-replication in a process known as the dimer
      catastrophe. Dimers are resolved to monomers by site-specific recombination
      systems such as Xer-cer of plasmid ColE1. In addition, the Rcd checkpoint
      hypothesis proposes that a short transcript (Rcd) coded within ColE1 cer delays
      the division of multimer-containing cells. The crucial observation underpinning
      the checkpoint hypothesis is that when the Rcd promoter (P(cer)) is inactivated
      by mutation of its invariant T, the plasmid becomes unstable. Recently, we
      discovered that this mutation also alters a potential Fis binding site in cer.
      ColE1-like plasmids are less stable in fis mutant hosts and it is conceivable
      that instability caused by the mutation is due to altered Fis binding, rather
      than the loss of Rcd expression per se. We have therefore undertaken an
      independent test of the role of P(cer)-Rcd in multicopy plasmid stability. We
      have generated a series of loss-of-function mutants of Rcd and detailed analysis
      of two of these shows that they cause a level of instability indistinguishable
      from P(cer) inactivation. This result is consistent with the predictions of the
      checkpoint hypothesis and confirms the role of Rcd in plasmid stability.

PMID- 16442620
TI  - In vivo and in vitro knockdown of FREP2 gene expression in the snail Biomphalaria
      glabrata using RNA interference.
AB  - RNA interference (RNAi) is reported here for the first time for Biomphalaria
      glabrata, the snail intermediate host for the human parasite Schistosoma mansoni.
      The fibrinogen-related protein 2 (FREP2) gene, normally expressed at increased
      levels following exposure to digenetic trematode parasites, such as S. mansoni or
      Echinostoma paraensei, was targeted for knockdown. Double-stranded RNA (dsRNA)
      corresponding to specific regions of the FREP2 gene was introduced into snails by
      direct injection into the hemolymph, 2 days prior to exposure to trematodes, or
      added to co-cultures of B. glabrata embryonic (Bge) cells and E. paraensei
      sporocysts. After introduction of FREP2 dsRNA, expression levels of FREP2 were
      significantly reduced, to 20-30% of control values. In addition, we were able to
      disrupt expression of the house-keeping myoglobin gene, further confirming the
      feasibility of RNAi for B. glabrata. Cross-reactivity in RNAi has not been
      observed either among four FREP gene subfamilies or between FREP2 and myoglobin.
      Establishment of RNAi techniques in B. glabrata provides an important tool for
      clarifying the function of genes believed to play a role in host-parasite
      interactions, specifically between B. glabrata and its trematode parasites,
      including S. mansoni.

PMID- 16442623
TI  - Signal sequences modulate the immunogenic performance of human hepatitis C virus
      E2 gene.
AB  - Envelope protein E2 of human hepatitis C virus (HCV) is an attractive component
      of a prototype HCV vaccine. Delivered by DNA immunogens, E2 evokes specific
      immune response of Th1-type, failing to induce either considerable antibody
      production, or T-helper cell proliferation. We aimed at modulating the
      immunogenic performance of E2 gene by changing the mode of protein expression in
      eukaryotic cells. Plasmids were constructed encoding full-length E2 and
      nonstructural protein 1 (p7) fused to either 13 or 38 C-terminal amino acids (aa)
      of HCV E1 that contain second hydrophobic segment of E1 stop-transfer signal, or
      a complete E1 stop-transfer signal with duplicated second hydrophobic segment.
      Injected into BALB/c mice, E2/p7 genes induced potent antibody and T-helper cell
      response targeted against hypervariable region 1, aa 472-586 of E2, and a novel
      epitope at aa 774-796 of p7. Profile of cytokines secreted by proliferating mouse
      splenocytes stimulated in vitro with E2- and p7-derived peptides, indicated mixed
      Th1/Th2 type of immune response. Thus, the full-length E2 and p7 genes supplied
      in one cassette were both immunogenic. E2/p7 containing a complete E1 stop
      transfer signal with prolonged membrane spanning domain was superior to the
      shorter E2/p7 version in terms of both antibody and cellular immunogenicity.
      Optimal performance of HCV E2 could thus be achieved without the aid of
      external/heterologous signals by easing, through modification of the E2 signal
      sequence, the release of E2 from the rough ER while retaining full-length E2 and
      p7 sequences. This finding may help to improve the Th2 performance of HCV
      envelope genes as prototype vaccines.

PMID- 16442622
TI  - Immunostimulatory oligodeoxynucleotide isolated from genome wide screening of
      Mycobacterium bovis chromosomal DNA.
AB  - Bacterial DNA has a variety of immunostimulatory activities, such as the
      activation of B cells and natural killer cells, the induction of interferon
      gamma, and the induction of Th1-type immune responses. In contrast, mammalian DNA
      does not have these activities. To evaluate the genomic DNA sequences of
      Mycobacterium bovis that have immunostimulatory activity, we used a computer to
      analyze the M. bovis genome and we designed a series of synthetic, 20 base
      length, phosphodiester backbone oligodeoxynucleotides (ODNs) that contain CpG
      motifs (MB-ODNs). We screened the immunostimulatory MB-ODNs that induce the
      activation of the NF-kappaB-responsive IL-8 promoter in RAW 264.7 cells. Our
      experimental analyses demonstrate that the potent CpG DNA in the M. bovis genome
      has functional effects as a Th1-responsive adjuvant, and that it activates the
      transcription factor NF-kappaB. Moreover, we found that both the CpG motifs and
      the context of the sequence surrounding the CpG motif are important for the
      immunostimulatory activities. The identification of the potent immunostimulatory
      DNA sequence in a native bacterial genome may give insights to the optimal
      sequence for well-controlled immune responses.

PMID- 16442624
TI  - The Kaposi's sarcoma-associated herpesvirus complement control protein (KCP)
      binds to heparin and cell surfaces via positively charged amino acids in CCP1-2.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV) complement control protein
      (KCP) inhibits the human complement system, and is similar in structure and
      function to endogenous complement inhibitors. Other inhibitors such as C4b
      binding protein and factor H, as well as the viral homologue vaccinia virus
      complement control protein are known to bind heparin and, for the two latter,
      also to glycosaminoglycans at the surface of cells. We report here that KCP also
      binds to heparin at physiological ionic strength. With help of site directed
      mutagenesis, positively charged amino acids in the two N-terminal complement
      control protein (CCP) domains 1-2 were found to be necessary for heparin binding.
      In silico molecular docking of heparin to KCP confirmed the experimental data,
      and further explored the heparin binding site, enabling us to present a model of
      the KCP-heparin interaction. Furthermore, the docking analysis also yielded
      insights of the KCP structure, by indicating that the angle between CCP domains 1
      2 during the initial binding of heparin is more extended than in the model we
      have previously presented. We also found that KCP binds to heparan sulfate and
      weakly to glycosaminoglycans at the surface of cells. This might indicate that
      KCP at the surface of viral particles aids in the primary attachment to the
      target cells, which is known to involve binding to heparan sulfate. Therefore,
      the present study contributes to the knowledge of heparin-protein interactions in
      general as well as to the understanding of the biology of KSHV.

PMID- 16442625
TI  - Dioxygen affinity in heme proteins investigated by computer simulation.
AB  - We present an investigation of the molecular basis of the modulation of oxygen
      affinity in heme proteins using computer simulation. QM-MM calculations are
      applied to explore distal and proximal effects on O(2) binding to the heme, while
      classical molecular dynamics simulations are employed to investigate ligand
      migration across the polypeptide to the active site. Trends in binding energies
      and in the kinetic constants are illustrated through a number of selected
      examples highlighting the virtues and the limitations of the applied
      methodologies. These examples cover a wide range of O(2)-affinities, and include:
      the truncated-N and truncated-O hemoglobins from Mycobacterium tuberculosis, the
      mammalian muscular O(2) storage protein: myoglobin, the hemoglobin from the
      parasitic nematode Ascaris lumbricoides, the oxygen transporter in the root of
      leguminous plants: leghemoglobin, the Cerebratulus lacteus nerve tissue
      hemoglobin, and the Alcaligenes xyloxidans cytochrome c'.

PMID- 16442626
TI  - Copper(II) interactions with non-steroidal anti-inflammatory agents. III--3
      Methoxyanthranilic acid as a potential *OH-inactivating ligand: a quantitative
      investigation of its copper handling role in vivo.
AB  - Pharmacological activities of copper(II) complexes are a direct function of the
      nature of their ligands associated with the metal ion in vivo. Some of these,
      defined as *OH-inactivating ligands (G. Berthon, Agents Actions 39 (1993) 210
      217), may act as specific "lures" for hydroxyl radicals at inflammatory sites and
      behave as pseudo-catalase-like agents. This property has been advanced for
      anthranilic acid (H. Miche, V. Brumas, G. Berthon, J. Inorg. Biochem. 68 (1997)
      27-38). With a view to improve the chemical features required to render such
      inactive substances effective anti-inflammatory drugs through their association
      with copper(II), an in vitro investigation into copper(II) interactions with the
      anionic form of an anthranilic acid derivative, namely 3-methoxyanthranilate
      (Man), has been performed under experimental conditions pertaining in vivo.
      Copper(II)-Man complex equilibria have been determined using glass electrode
      potentiometry, then checked by UV-vis and mass spectrometries. Given the prime
      role of histidine as a copper(II) ligand in blood plasma, copper(II)-histidine
      Man ternary equilibria have also been studied. Subsequent computer simulations of
      the distribution of copper(II) in the extracellular fluid revealed that Man can
      specifically mobilize Cu(II) ions under inflammatory conditions without affecting
      their distribution under normal physiological conditions. Thiobarbituric acid
      reactive substances (TBARS) tests conducted with respect to standardized copper
      mediated Fenton-type reactions (P. Maestre, L. Lambs, J.P. Thouvenot, G. Berthon,
      Free Rad. Res. 20 (1994) 205-218) have shown that, like anthranilic acid, Man can
      effectively both increase the Fenton-like reactivity of copper and decrease the
      amount of TBARS detected in solution, i.e., act as a potential *OH-inactivating
      ligand.

PMID- 16442627
TI  - Mossbauer identification of a protonated ferryl species in catalase from Proteus
      mirabilis: density functional calculations on related models.
AB  - The Proteus mirabilis catalase is one of the most efficient heme-containing
      catalase and forms a relatively stable compound II. Samples of compound II were
      prepared from PMC enriched in (57)Fe. For the first time, two different forms of
      compound II, namely low pH compound II (LpH II) (43%) and high pH compound II
      (HpH II) (25%), have been characterized by Mossbauer spectroscopy at pH 8.3. The
      ratio LpH II/HpH II increases irreversibly with decreasing pH. The large
      quadrupole splitting value of LpH II (DeltaE(Q)=2.29 (2) mm/s, with
      delta(/Fe)=0.03 (2) mm/s), compared to that of HpH II (DeltaE(Q)=1.47 (2) mm/s,
      with delta(/Fe)=0.07 (2) mm/s), reflects the protonation of the ferryl group.
      Quadrupole splitting values of 1.46 and 2.15mm/s have been computed by DFT for
      optimized models of the ferryl compound II (model 1) and the protonated ferryl
      compound II (model 2), respectively, starting from the Fe(IV)O model initially
      published by Rovira and Fita [C. Rovira, I. Fita, J. Phys. Chem. B 107 (2003)
      5300-5305]. Therefore, we attribute the LpH II compound to a protonated ferryl
      Fe(IV)-OH complex, whereas the HpH II compound corresponds to the classical
      ferryl Fe(IV)O complex.

PMID- 16442628
TI  - Three rare cases of anthrax arising from the same source.
AB  - Anthrax is an acute bacterial infection caused by Bacillus anthracis. Humans
      become infected under natural conditions by contact with infected animals or
      contaminated animal products. About 95% of human anthrax is cutaneous and 5%
      respiratory. Gastrointestinal anthrax is very rare, and has been reported in less
      than 1% of all cases. Anthrax meningitis is a rare complication of any of the
      other three forms of disease. We report three rare cases of anthrax
      (gastrointestinal, oropharyngeal and meningitis) arising from the same source.
      The three patients were from a single family and were admitted with different
      clinical pictures after the ingestion of half-cooked meat from a sick sheep.
      These cases emphasize the need for awareness of anthrax in the differential
      diagnosis in areas where the disease remains endemic.

PMID- 16442629
TI  - Protective efficacy of intranasal vaccination with Mycobacterium bovis BCG
      against airway Mycobacterium tuberculosis challenge in mice.
AB  - The effect of route of immunization on the protective efficacy of BCG against
      tuberculosis has been investigated. Immunoprotection was monitored by evaluating
      the bacterial burden in the lungs and spleen of mice challenged with
      Mycobacterium tuberculosis H(37)Rv after BCG immunization by intranasal (i.n.)
      and subcutaneous (s.c.) routes. Our results showed that as compared to s.c. BCG
      immunization, intranasal BCG vaccination induces significantly higher immune
      responses at local level (mediastinal lymph nodes, cervical lymph nodes and
      lung). Further, i.n. BCG vaccination induced significantly higher reduction in
      bacterial load in the lungs over s.c. BCG vaccination, whereas, the bacilli load
      in the spleen was comparable in both the groups. Hence, intranasal vaccination
      with BCG holds promise for pulmonary tuberculosis.

PMID- 16442630
TI  - Serosurveillance of acute Mycoplasma pneumoniae infection among HIV infected
      patients with pulmonary complaints in Chennai, Southern India.
AB  - BACKGROUND: The true seroepidemiology of acute Mycoplasma pneumoniae infection in
      HIV infected individuals is ambiguous. METHODS: This study examined the
      serosurveillance of IgM antibodies to M. pneumoniae in HIV infected patients
      presenting with pulmonary symptoms at a tertiary AIDS care center in Chennai,
      Southern India, using cold-haemagglutination test and commercial enzyme linked
      immunosorbent assay in acute serum specimens. RESULTS: One hundred HIV infected
      patients had enrolled in the study; 21 (21%) were positive for M. pneumoniae IgM
      antibodies by ELISA and 34 (34%) showed evidence of cold hemagglutinins.
      CONCLUSION: This serosurveillance study reports a 21% prevalence of M. pneumoniae
      IgM antibody among HIV infected patients with pulmonary symptoms by ELISA and non
      specific diagnosis was confirmed in 34% of the cases screened. Determination of
      cold agglutination titer could be used as a substitute to other expensive
      procedures in limited resource settings and third-world nations to diagnose M.
      pneumoniae infections for prompt initiation of therapy, as CAT has been found to
      be 100% sensitive and 84% specific in the diagnosis of M. pneumoniae infection.

PMID- 16442631
TI  - Correlation between rainfall and the prevalence of malaria in Thailand.
AB  - Malaria is the most important parasitic disease of people, affecting over 200
      million people and causing more than one million deaths each year. Presently, the
      Southeast Asia including Thailand is still the endemic are for malaria. The
      surveys of the disease prevalence are useful for prevention and control of
      disease [Phillips RS. Current status of malaria and potential for control. Clin
      Microbiol Rev 2001;14:208-26] and have been continuously performed in Thailand.
      The correlation between rainfall and infection rate of malaria is of interest.
      Here, the correlation between the rainfall and the prevalence of malaria was
      investigated. The relation between the rainfall (transformed from the
      geographical data) and the prevalence of malaria (transformed from the overall
      infection rate of malaria) is investigated. The least square equation plot
      rainfall (Y) vs. prevalence (X) is Y=24.82X+987.84 (r=0.76, P<0.01). In
      conclusion, the prevalence of malarial infection in Thailand may depend on
      rainfall. Therefore, the surveillance and control of mosquito during the period
      with high rainfall is recommended. Further, similar study to assess the
      correlation between the rainfall and prevalence of infection in the other
      countries is required to fulfill the conclusion.

PMID- 16442632
TI  - Colistin and rifampicin in the treatment of nosocomial infections from
      multiresistant Acinetobacter baumannii.
AB  - INTRODUCTION: The increased incidence of nosocomial infections by multi-drug
      resistant Acinetobacter baumannii creates demand on the application of some
      combinations of older antimicrobials on that species. We conducted the present
      observational study to evaluate the efficacy of intravenous and aerosolized
      colistin combined with rifampicin in the treatment of critically patients with
      nosocomial infections caused by multiresistant A. baumannii. PATIENTS AND
      METHODS: Critically ill patients with nosocomial infections caused by A.
      baumannii resistant to all antibiotics except colistin in a medical intensive
      care unit. Diagnosis of infection was based on clinical data and isolation of
      bacteria. The bacterial susceptibilities to colistin were tested. Clinical
      response to colistin+rifampicin was evaluated. RESULTS: Twenty-six patients
      (43.58+/-18.29 years, Acute Physiology and Chronic Health Evaluation II Score
      (APACHE II): 6.35+/-2.99), of whom 16 cases of nosocomial pneumonia treated by
      aerosolized colistin (1x10(6) IU three times/day) associated with intravenous
      rifampicin (10 mg/kg every 12h), nine cases of bacteraemia treated by intravenous
      colistin (2x10(6)IU three times/day) associated with intravenous rifampicin (10
      mg/kg every 12h) in which three cases associated with ventilator associated
      pneumonia and one case of nosocomial meningitis treated by intrathecal use of
      colistin associated with intravenous rifampicin. The clinical evolution was
      favourable for all ill patients. Concerning side effects, we have noticed a
      moderate hepatic cytolysis in three patients. CONCLUSION: This is the first
      clinical report of colistin combined with rifampicin for treatment of A.
      baumannii infection. Despite the lack of a control group and the limited number
      of patients, the results seem to be encouraging.

PMID- 16442633
TI  - Mechanisms of the adaptive immune response inside the central nervous system
      during inflammatory and autoimmune diseases.
AB  - In this review we will discuss the unique features that make the central nervous
      system (CNS) a specialized microenvironment where immune responses are tightly
      regulated in order to properly face pathogens without damaging the neural cells.
      We will show how every paradigm of this theoretical model has been addressed by
      the scientific literature over the past decades providing new insights on the
      immune response within the CNS. In particular, new light has been shed on the
      trafficking of the immune cells inside and outside the CNS. Dendritic cells (DCs)
      have been described in the context of structures in direct contact with the
      cerebrospinal fluid (CSF) and their migration, upon antigen encounter, outside
      the CNS into deep cervical lymph nodes (DCLNs) has been further clarified. T
      cells, B-cells, and antibody-secreting cells (ASCs) have been found in the CSF
      and CNS parenchymal lesions of inflammatory disorders and their phenotype
      depicted. Moreover, in chronically inflamed CNS, ectopic lymphoid structures have
      been observed and a germinal center reaction similar to the one found in
      peripheral lymph nodes has been described. These structures may play a role in
      the maintenance and expansion of the local autoimmune response. Although the
      complex interactions between immune and neural cells still remain far to be
      elucidated, the data discussed here suggest that the physiopathology of the
      adaptive immune response inside the CNS mimics, although in a mitigated fashion,
      what occurs in other organs and tissues.

PMID- 16442634
TI  - Determination of microcystins in environmental samples using capillary
      electrophoresis.
AB  - The applicability of capillary zone electrophoresis (CZE) and micellar
      electrokinetic chromatography (MEKC) methods for the simultaneous determination
      of two frequently occurring microcystins (MCs-LR and -YR) and a new variant (MC
      YA) in crude extracts of Hungarian bloom samples and cyanobacterial cultures was
      studied. It was found that the comparison of the results obtained by both CZE and
      MEKC measurements (due to the differences in their separation mechanisms) for the
      same sample can guarantee the reliability of the quantitative results. In our
      work environmental samples like lake waters, water bloom samples, cyanobacterial
      isolates were analysed. The three microcystins could be directly determined in
      water bloom samples collected from Hungarian lakes and laboratory culture samples
      of cyanobacteria.

PMID- 16442635
TI  - Microarray-based methylation analysis using dual-color fluorescence
      hybridization.
AB  - BACKGROUND: Aberrant DNA methylation of CpG sites is among the earliest and most
      frequent alterations in cancer. It is of great importance to develop simple, high
      throughput and quantitative methods for methylation detection. METHODS: A high
      throughput methylation analysis method has been developed based on microarray and
      dual-color fluorescence hybridization. The genomic DNA was treated with
      bisulfite, resulting in conversion of non-methylated cytosine, but not methylated
      cytosine, into uracil within CpG islands of interest. PCR products of the treated
      genomic templates were spotted and immobilized onto a poly-l-lysine coated glass
      slide to fabricate a microarray and then interrogated by hybridization with dual
      color probes to determine the methylation status. The hybridized signals were
      obtained with a scanner and the results were analyzed with the software Genepix
      Pro 3.0. RESULTS: The methylation status of the CpG islands of IGFBP7 gene has
      been successfully evaluated by the microarray method for twenty-seven samples.
      All the investigated samples, including twenty human breast tumor tissues, six
      corresponding normal human breast tissues and one liver cell line, all CpG sites
      were found completely methylated. CONCLUSIONS: The microarray technology has been
      proven to have potential for high-throughput detection of the methylation status
      for a given gene in multi-genomic samples, which could be a novel approach for
      rapidly screening DNA methylation marker for early stage cancer diagnosis.

PMID- 16442636
TI  - Application of multiline two-photon microscopy to functional in vivo imaging.
AB  - High spatial resolution and low risks of photodamage make two-photon laser
      scanning microscopy (TPLSM) the method of choice for biological imaging. However,
      the study of functional dynamics such as neuronal calcium regulation often also
      requires a high temporal resolution. Hitherto, acquisition speed is usually
      increased by line scanning, which restricts spatial resolution to structures
      along a single axis. To overcome this gap between high spatial and high temporal
      resolution we performed TPLSM with a beam multiplexer to generate multiple laser
      foci inside the sample. By detecting the fluorescence emitted from these laser
      foci with an electron-multiplying camera, it was possible to perform multiple
      simultaneous linescans. In addition to multiline scanning, the array of up to 64
      laser beams could also be used in x-y scan mode to collect entire images at high
      frame rates. To evaluate the applicability of multiline TPLSM to functional in
      vivo imaging, calcium signals were monitored in visual motion-sensitive neurons
      in the brain of flies. The capacity of our method to simultaneously acquire
      signals at different cellular locations is exemplified by measurements at
      branched neurites and 'spine'-like structures. Calcium dynamics depended on
      branch size, but 'spines' did not systematically differ from their 'parent
      neurites'. The spatial resolution of our setup was critically evaluated by
      comparing it to confocal microscopy and the negative effect of scattering of
      emission light during image detection was assessed directly by running the setup
      in both imaging and point-scanning mode.

PMID- 16442637
TI  - Insight, symptoms and neurocognition in bipolar I patients.
AB  - BACKGROUND: Level of insight and its relationship to clinical variables and
      neurocognitive functions was assessed in bipolar I patients. METHODS: Verbal
      memory, executive functioning, sustained attention, general intelligence and
      other neurocognitive functions were compared between 37 chronic in- and
      outpatients and 31 matched normal controls. Detailed psychiatric interviews were
      completed to define the level of symptomatology and psychosocial functioning.
      Insight was assessed by the Scale to Assess Unawareness of Mental Disorder
      (SUMD). RESULTS: Seventy percent of the patients were classified as having
      impaired insight. Prevalence of impaired insight was 47% and 94% in remitted and
      symptomatic patients, respectively. Symptomatic patients scored significantly
      below remitted patients on insight and neurocognition. Illness and symptom
      unawareness were related to overall level of symptoms, measures of memory,
      conceptual ability and right hand psychomotor speed and accuracy. Misattribution
      of symptoms and signs was correlated to visuomotor speed and visuospatial
      performance in addition to affective symptoms and thought disturbance.
      CONCLUSIONS: Our findings support the hypothesis that impaired insight and other
      neurocognitive dysfunctions were present in a large percentage of cases among
      symptomatic as well as remitted bipolar patients. This may be of clinical
      relevance and raises important questions about the course and outcome of the
      illness.

PMID- 16442638
TI  - Can personality assessment predict future depression? A twelve-month follow-up of
      631 subjects.
AB  - BACKGROUND: Personality assessment provides a description of a person's
      fundamental emotional needs and of the higher cognitive processes that modulate
      thoughts, feelings, and behavior. Prior studies by us examined personality and
      mood at the same time. Assessing personality may allow prediction of mood changes
      over time in a longitudinal study, as described in earlier prospective studies by
      Paula Clayton and others. METHOD: A group of 631 adults representative of the
      general population completed the Temperament and Character Inventory (TCI) and
      Center for Epidemiological Studies depression scale (CES-D) at baseline and one
      year later. RESULTS: TCI scores at baseline accounted for gender differences in
      levels of depression. TCI personality scores were strongly stable (range in r=.78
      to .85 for each of seven dimensions) whereas mood was only moderately stable
      (r=.62) over the twelve-month follow-up. Baseline personality scores
      (particularly high Harm Avoidance and low Self-Directedness) explained 44% of the
      variance in the change in depression. Baseline levels and changes in Harm
      Avoidance and Self-Directedness explained 52% of the variance in the change in
      depression at follow-up. LIMITATIONS: The follow-up sample was representative of
      the target population except for slightly lower Novelty Seeking scores. CLINICAL
      RELEVANCE: Observable personality levels strongly predict mood changes.
      Personality development may reduce vulnerability to future depression.

PMID- 16442640
TI  - How safe is paediatric tonsillectomy?

PMID- 16442639
TI  - Capture of antigen-specific T lymphocytes from human blood by selective
      immortalization to establish long-term T-cell lines maintaining primary cell
      characteristics.
AB  - To establish long-term, antigen-specific T-cell lines and clones, we selectively
      immortalized antigen-responsive T cells from human peripheral blood mononuclear
      cells (PBMCs). PBMCs were stimulated with either alloantigen or soluble antigen,
      then infected with a murine leukemia virus-based retroviral vector carrying an
      immortalizing gene, either the Tax gene from human T-cell leukemia virus type 1,
      or the human telomerase-reverse transcriptase gene. Since such vectors can only
      integrate in dividing cells, only antigen-activated T cells are efficiently
      transduced. This approach generated immortalized antigen-specific CD4+ and CD8+ T
      cell lines that maintained strictly IL-2-dependent growth and HLA-restricted,
      antigen-specific responsiveness, some of which have been in continuous culture
      for longer than 1 year, far in excess of the survival of parallel control non
      immortalized cultures. Clones derived from these lines showed antigen-specific
      proliferation with induced cytokine and chemokine production, and, in the case of
      a CD8+ T-cell clone, antigen-specific cytolytic activity. This approach provides
      a convenient, reproducible means for generating a stable, continuously renewable
      source of antigen-specific T lymphocytes for a variety of studies of T cell
      biology.

PMID- 16442641
TI  - Time course of cross-hemispheric spatial updating in the human parietal cortex.
AB  - In human parietal cortex, the retinal location of a just seen visual stimulus is
      updated from one hemisphere to the other, when a horizontal eye movement brings
      the representation of the stimulus into the opposite visual hemifield. The
      present study aimed to elucidate the time course of this process. Twelve subjects
      performed an updating task, in which a filled circle was shown before a
      horizontal saccade, requiring updating of stimulus location, and a control task
      without visual stimulation before the saccade. Electroencephalogram (EEG) and
      electrooculogram (EOG) were recorded while subjects performed the tasks and
      LORETA source analysis was performed on event-related potential (ERP) components.
      ERP amplitudes were more positive in the updating condition in comparison to the
      control condition in two latency windows. An early positive wave starting at
      about 50 ms after saccade offset and originating in the posterior parietal cortex
      contralateral to saccade direction probably reflects the integration of saccade
      related and visual information and thus the updating process. A shift of the
      representation of the to-be-updated stimulus to the opposite hemisphere is
      reflected in a later component starting approximately 400 ms after saccade
      offset, which is related to memory and originates in the PPC ipsilateral to
      saccade direction and thus contralateral to the spatial location of the updated
      visual stimulus.

PMID- 16442643
TI  - Identification and characterization of EhABC A1, an Entamoeba histolytica Group A
      ABC transporter with similarity to Ced-7.

PMID- 16442642
TI  - Deletion of copies of the gene encoding old yellow enzyme (TcOYE), a NAD(P)H
      flavin oxidoreductase, associates with in vitro-induced benznidazole resistance
      in Trypanosoma cruzi.
AB  - Old yellow enzyme (OYE) is a NAD(P)H flavin oxidoreductase that in Trypanosoma
      cruzi (TcOYE) catalyzes prostaglandin PGF2alpha synthesis and reduction of some
      trypanocidal drugs. We performed DNA microarray analysis and it revealed that the
      levels of transcription of the TcOYE gene were six-fold lower in a T. cruzi
      population with in vitro-induced resistance to benznidazole (BZ) (17LER) than in
      the wild-type (17WTS). Further we investigated the TcOYE levels in 15 T. cruzi
      strains and clones that were either susceptible or naturally resistant to BZ and
      nifurtimox, or had in vivo-selected resistance to BZ. Northern blot and real-time
      RT-PCR analyses confirmed our finding that TcOYE transcription levels were lower
      in 17LER than in 17WTS. In contrast, we detected no differences in TcOYE
      transcription levels between other T. cruzi samples. All T. cruzi strains
      contained four copies of TcOYE gene, except 17LER that contained only one. A
      42kDa TcOYE protein was detected in all T. cruzi strains tested. The expression
      of this protein was similar for all samples, with the exception of 17LER for
      which the protein was nearly seven-fold less expressed. The chromosomal location
      of the TcOYE gene and the polymorphisms detected in TcOYE nucleotide and amino
      acid sequences of the T. cruzi strains are associated with the zymodeme but not
      with drug-resistance phenotype. Our data show that one of the mechanisms
      conferring in vitro-induced BZ resistance to T. cruzi correlates with deletion of
      copies of the TcOYE gene. In contrast, the in vivo and natural resistance to BZ
      are mediated by different mechanisms.

PMID- 16442644
TI  - Menopause: a review on the role of oxygen stress and favorable effects of dietary
      antioxidants.
AB  - Menopause is often accompanied by hot flashes and degenerative processes such as
      arteriosclerosis and atrophic changes of the skin that suggest an acceleration of
      aging triggered by estrogen lack. Therefore, hormone replacement therapy (HRT)
      has been considered the most suitable treatment for the above symptoms and
      processes. However, because of the possible serious side effects of HRT
      (especially the increased risk of thrombo-embolic accidents and breast cancer)
      there is a growing demand for alternative treatments of the symptoms and
      pathological processes associated with menopause. In agreement with the above, we
      review research that supports the concept that oxygen stress contributes to
      menopause and that some of its physiopathological effects may be prevented and/or
      treated improving the antioxidant defense of menopausic and postmenopausic women.
      Accordingly, a selection of micronutrients may be useful as a dietary supplement
      for protection against the decline of physiological functions caused by age
      related oxygen stress. Since aging is accompanied by a progressive oxidation of
      the physiological sulfur pool, we emphasize the role of the vitamins B that help
      to maintain the GSH/GSSG ratio in its normal reduced state. Nutritional
      supplements should also include the key antioxidant vitamins C and E, as well as
      beta-carotene and the mineral micronutrients found in the oxygen radical
      detoxifying enzymes glutathione peroxidase and superoxide dismutase. Moreover,
      the reviewed data suport the concept that other antioxidants such as lipoic acid
      and the precursors of glutathione thioproline (TP) and l-2-oxothiazolidine-4
      carboxylic acid (OTC), as well as the soy isoflavones and the "coantioxidants" of
      an hydroalcoholic extract of Curcuma longa may help to prevent antioxidant
      deficiency with resulting protection of mitochondria against premature oxidative
      damage with loss of ATP synthesis and especialized cellular functions. Therefore,
      the administration under medical advice of synergistic combinations of some of
      the above mentioned antioxidants in the diet as well as topically (for skin
      protection) may have favorable effects on the health and quality of life of
      women, especially of those who cannot be treated with HR, suffer high levels of
      oxygen stress, and do not consume a healthy diet that includes five daily rations
      of fresh fruit and vegetables.

PMID- 16442646
TI  - Genetic testing in competitive insurance markets with repulsion from chance: a
      welfare analysis.
AB  - A central theme in the international debate on genetic testing concerns the
      extent to which insurance companies should be allowed to use genetic information
      when offering insurance contracts. We provide a welfare analysis of this issue
      within a model of an insurance market with asymmetric information, having the
      following crucial feature: in addition to a state-contingent consumption profile,
      a person's well-being depends on her attitude towards resolution of future health
      uncertainty, and this attitude varies across the population. We present stylized
      facts that motivate this approach. In the formal analysis, we find that both
      tested high-risks and untested individuals are equally well off whether or not
      test results can be used by insurers. Individuals who test for being low-risks,
      on the other hand, are made worse off by not being able to verify this to
      insurers. This implies that, in terms of welfare, a regulatory regime in which
      the use of genetic information by insurers is allowed is better than one in which
      it is not allowed.

PMID- 16442647
TI  - Comment on: osteopontin as toxic marker.

PMID- 16442649
TI  - Accuracy of drawing in a dual-task and resistance-to-distraction study: motor or
      attention deficit?
AB  - To determine whether manual incoordination is caused by attention deficit or not,
      we used an accuracy drawing task as a primary task in dual-task and resistance-to
      distraction studies, and examined if thus measured attention could differentiate
      inattention (IA) and combined (CO) subtypes of ADHD. The secondary tasks and
      distractions failed to lower the primary task performance in IA, CO and control
      groups. We also compared the impairment scores of the accuracy drawing tasks from
      the Movement Assessment Battery for Children [Henderson, S. E., & Sugden, D. A.
      (1992). Movement assessment battery for children. London: Psychological
      Corporation.] between the groups with attention deficit hyperactivity disorder
      (ADHD) and/or developmental coordination disorder-inaccurate drawing type (DCD
      ID). There were no group differences in the impairment score between the control
      and the ADHD groups, and between ADHD and ADHD plus DCD-ID groups. We concluded
      that inaccurate drawing is not caused by attention deficit, but that it is a
      manifestation of a motor deficit as a separate entity from attention deficit.

PMID- 16442650
TI  - DCD and ADHD: a genetic study of their shared aetiology.
AB  - Previous studies have found that rates of attention deficit hyperactivity
      disorder (ADHD) and developmental coordination disorder (DCD) are very similar,
      both being approximately 7% in sample populations [Kadesjo, B., & Gillberg, C.
      (1999). Developmental coordination disorder in Swedish 7-year-old children.
      Journal of the American Academy of Child and Adolescent Psychiatry, 38, 820-828;
      Milberger, S., Faraone, S., Biederman, J., Testa, M., & Tsuang, M. (1996). New
      phenotype definition of attention deficit hyperactivity disorder in relatives for
      genetic analyses. American Journal of Medical Genetics, 67, 369-377]. The rate of
      comorbidity between the two has been found to be close to 50% [Barkley, R.
      (1990). Attention deficit hyperactivity disorder: A handbook for diagnosis and
      treatment. New York: Guilford Press]. Investigations into the comorbidity of the
      disorders points to a shared aetiology between them. The aim of the present
      investigation was to examine the extent to which the shared aetiology is due to
      common genetic factors to both disorders. We also investigated whether particular
      subtypes of each disorder were more linked than others. Mailed questionnaires
      were completed by parents (predominantly mothers) of 1285 twin pairs aged 5 and
      16 years from the volunteer Australian Twin Registry (ATR). Included were a DSM
      IV-based ADHD form, the alternative SWAN (Strengths and Weaknesses of ADHD
      Symptoms and Normal Behaviour scale) and the Developmental Coordination Disorder
      Questionnaire (DCDQ). Statistical analyses including structural equation
      modelling were carried out to explore the genetic factors of both disorders. The
      modelling showed a strong shared additive genetic component between most subtypes
      of ADHD and DCD to the subtypes of the other disorder. Analyses comparing the two
      ADHD measures showed an overlap of the symptoms captured by each measure but also
      significant differences. The DCD-fine motor and ADHD-Inattentive were most
      strongly linked using the DSM-IV based scale. On the SWAN scale the results were
      similar but the general coordination scale was also very strongly linked.
      Implications for the use of different assessment tools are discussed.

PMID- 16442651
TI  - Chemical tools for activity-based proteomics.
AB  - Several approaches for proteome analysis and the generation of proteome subsets
      rely on engineered chemical probes that are tailored towards the detection of
      different protein classes. The concepts are presented in this review covering the
      literature until mid-2005.

PMID- 16442652
TI  - Hin4II, a new prototype restriction endonuclease from Haemophilus influenzae
      RFL4: discovery, cloning and expression in Escherichia coli.
AB  - The genes encoding restriction-modification system of unknown specificity Hin4II
      from Haemophilus influenzae RFL4 were cloned in Escherichia coli and sequenced.
      The Hin4II system comprises three tandemly arranged genes coding for m6A DNA
      methyltransferase, m5C DNA methyltransferase and restriction endonuclease,
      respectively. Restriction endonuclease was expressed in E. coli and purified to
      apparent homogeneity. The DNA recognition sequence and cleavage positions were
      determined. R.Hin4II recognizes the novel non-palindromic sequence 5'-CCTTC-3'
      and cleaves the DNA 6 and 5 nt downstream in the top and bottom strand,
      respectively. The new prototype restriction endonuclease Hin4II was classified as
      a potential candidate of HNH nuclease family after comparison against SMART
      database. An amino acid sequence motif 297H-X14-N-X8-H of Hin4II was proposed as
      forming a putative catalytic center.

PMID- 16442653
TI  - Affinity binding of inclusion bodies on supermacroporous monolithic cryogels
      using labeling with specific antibodies.
AB  - A new chromatographic method based on affinity supermacroporous monolithic
      cryogels is developed for binding and analyzing inclusion bodies during
      fermentation. The work demonstrated that it is possible to bind specific IgG and
      IgY antibodies to the 15 and 17 amino acids at the terminus ends of a 33 kDa
      target protein aggregated as inclusion bodies. The antibody treated inclusion
      bodies from lysed fermentation broth can be specifically retained in protein A
      and pseudo-biospecific ligand sulfamethazine modified supermacroporous cryogels.
      The degree of binding of IgG and IgY treated inclusion bodies to the Protein A
      and sulfamethazine gels are investigated, as well as the influence of pH on the
      sulfamethazine ligand. Optimum binding of 78 and 72% was observed on both protein
      A and sulfamethazine modified cryogel columns, respectively, using IgG labeling
      of the inclusion bodies. The antibody treated inclusion bodies pass through
      unretained in the sulfamethazine supermacroporous gel at pH that does not favour
      the binding between the ligand on the gel and the antibodies on the surface of
      inclusion bodies. Also the unlabeled inclusion bodies went through the gel
      unretained, showing no non-specific binding or trapping within the gel. These
      findings may very well be the foundation for the building of a powerful
      analytical tool during fermentation of inclusion bodies as well as a convenient
      way to purify them from fermentation broth. These results also support our
      earlier findings [Kumar, A., Plieva, F.M., Galaev, I.Yu., Mattiasson, B., 2003.
      Affinity fractionation of lymphocytes using a monolithic cyogel. J. Immunol.
      Methods 283, 185-194] with mammalian cells that were surface labeled with
      specific antibodies and recognized on protein A supermacroporous gels. A general
      binding and separation system can be established on antibody binding cryogel
      affinity matrices.

PMID- 16442654
TI  - Total amino acid stabilization during cell-free protein synthesis reactions.
AB  - Limitations in amino acid supply have been recognized as a substantial problem in
      cell-free protein synthesis reactions. Although enzymatic inhibitors and fed
      batch techniques have been beneficial, the most robust way to stabilize amino
      acids is to remove the responsible enzymatic activities by genetically modifying
      the source strain used for cell extract preparation. Previous work showed this
      was possible for arginine, serine, and tryptophan, but cysteine degradation
      remained a major limitation in obtaining high protein synthesis yields. Through
      radiolabel techniques, we confirmed that cysteine degradation was caused by the
      activity of glutamate-cysteine ligase (gene gshA) in the cell extract. Next, we
      created Escherichia coli strain KC6 that combines a gshA deletion with previously
      described deletions for arginine, serine, and tryptophan stabilization. Strain
      KC6 grows well, and active cell extract can be produced from it for cell-free
      protein synthesis reactions. The extract from strain KC6 maintains stable amino
      acid concentrations of all 20 amino acids in a 3-h batch reaction. Yields for
      three different proteins improved 75-250% relative to cell-free expression using
      the control extract.

PMID- 16442655
TI  - Synthesis of the food flavoring methyl benzoate by genetically engineered
      Saccharomyces cerevisiae.
AB  - Current means of production for plant-derived aroma compounds include chemical
      synthesis and extraction from plant material. Both methods are environmentally
      detrimental and relatively expensive: plant material is only seasonally available
      and only a small subset of the plant biomass produces the desired aroma
      compounds, while organic synthesis inevitably involves waste byproducts with a
      negative ecological impact. Benzenoids are a class of plant metabolites that
      includes a number of aroma compounds. This paper explores, for the first time,
      the feasibility of producing benzenoids in yeast. We present a method for the
      production of the phenylpropanoid methyl benzoate in Saccharomyces cerevisiae
      using benzoic acid as a substrate, by heterologous expression of Antirrhinum
      majus benzoic acid methyl transferase. Production was pH dependent with a maximal
      yield of approximately 50 microg of methyl benzoate per liter of culture per
      hour, and with linear kinetics over at least 24 h. In addition, we have analyzed
      two alternative expression vectors for the production of benzoic acid methyl
      transferase in S. cerevisiae: a constitutive triosephosphate isomerase promoter
      based system was compared with a copper-inducible CUP1 promoter system. We find
      major differences in the amounts of methylbenzoate produced by these respective
      systems. Potential applications are discussed.

PMID- 16442656
TI  - Enhancing the tolerance of zebrafish (Danio rerio) to heavy metal toxicity by the
      expression of plant phytochelatin synthase.
AB  - Phytochelatin synthase (PC synthase) catalyzes a biosynthesis of phytochelatins
      (PCs), which are small molecules and glutathione (GSH)-derived metal-binding
      peptides that are essential for the detoxification of heavy metal ions in plants,
      fungi and worms. In order to enhance tolerance to heavy metal cytotoxicity, mRNA
      coding for PC synthase from Arabidopsis thaliana (AtPCS1) was introduced into the
      early embryos of zebrafish. As a result, the heterogeneous expression of PC
      synthase and the synthesis of PCs from GSH in embryos could be detected. The
      developing embryos expressing PC synthase (PC-embryos) became more tolerant to Cd
      toxicity (500 microM exposure). PC-embryos had significantly longer apparent
      lethal times for 50% of the population (LT50) of 8.17+/-1.08 days, although
      control embryos had apparent LT50 of 5.43+/-0.66 days. These data suggest that PC
      synthase can function in developmental zebrafish, and that PCs are highly
      effective in detoxifying Cd toxicity even in the whole body of a vertebrate
      species.

PMID- 16442657
TI  - Fish transposons and their potential use in aquaculture.
AB  - A large part of repetitive DNA of vertebrate genomes have been identified as
      transposon elements (TEs) or mobile sequences. Although TEs detected to date in
      most vertebrates are inactivated, active TEs have been found in fish and a
      salmonid TE has been successfully reactivated by molecular genetic manipulation
      from inactive genomic copies (Sleeping Beauty, SB). Progress in the understanding
      of the dynamics, control and evolution of fish TEs will allow the insertion of
      selected sequences into the fish genomes of germ cells to obtain transgenics or
      to identify genes important for growth and/or of somatic cells to improve DNA
      vaccination. Expectations are high for new possible applications to fish of this
      well developed technology for mammals. Here, we review the present state of
      knowledge of inactive and active fish TEs and briefly discuss how their possible
      future applications might be used to improve fish production in aquaculture.

PMID- 16442658
TI  - Thermoswitched immobilization-a novel approach in reversible immobilization.
AB  - The present work is based on the finding that the mesophilic carbohydrate-binding
      domain from Clostridium cellulovorans fused with thermophilic enzymes from
      Pyrococcus furiosus can be reversibly denaturated and renaturated by a simple
      switch of temperature. Modular recombinant enzymes are active and free in the
      reaction mixture at 80-90 degrees C and deactivated and immobilized by affinity
      adsorption on cellulose at 40-30 degrees C. The temperature transition between
      both modes is rather sharp and occurs within the range of 40-50 degrees C. Due to
      the elevated temperature, there is no limitation by a diffusion step, and
      contamination does not occur during the reaction. After the reaction, the enzymes
      are quickly deactivated, adsorbed on the affinity matrix, removed from the
      reaction mixture, and ready for use in another reaction cycle.

PMID- 16442659
TI  - Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to
      Lithuanian children with type 1 diabetes.
AB  - We compared the prevalence of beta-cell autoantibodies and genetic risk factors
      in Sweden and Lithuania. Ninety-six patients from Sweden and 96 from Lithuania
      matched for age and gender (1-15 years old, median age 9.0 years) were included.
      We analyzed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA)
      and the protein tyrosine phosphatase like IA-2 (IA-2A) as well as risk-associated
      polymorphisms of HLA, insulin and cytotoxic T-lymphocyte-associated protein 4
      (CTLA-4) genes. The frequency of patients positive for IAA and GADA was higher in
      Sweden than in Lithuania (p = 0.043 and 0.032). The differences remained even
      when the patients were matched for HLA, insulin and CTLA-4 risk genotypes.
      Patients with low levels of IAA had higher levels of HbA1c and ketones at
      diagnosis. The frequency of the risk haplotype DR4-DQ8 was higher in Swedish than
      in Lithuanian patients (p = 0.004), as well as the high-risk combination of DR4
      DQ8 and DR3-DQ2 haplotypes (p = 0.009). Our results suggest that autoimmune
      process against insulin and GAD(65) is more common at diagnosis in children in
      areas with high incidence of type 1 diabetes (T1D), independent of genetic risk
      markers. Furthermore, the disease in patients with insulin autoantibodies seems
      to be clinically milder.

PMID- 16442660
TI  - Glycaemic control, markers of endothelial cell activation and oxidative stress in
      children with type 1 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to compare the effect of glycaemic control
      on oxidative stress and biochemical markers of endothelial activation in type 1
      diabetic children. METHODS: Serum total cholesterol, HDL cholesterol, VLDL
      cholesterol, apolipoprotein A1, apolipoprotein B, HbA(1c), MDA, VEGF, NO, ICAM
      levels were assessed in 100 children with type 1 DM aged 2-17 years. Study cases
      were evaluated in three groups in view of their mean HbA(1c) values, as
      metabolically well-controlled (HbA(1c)< or =8%) and poorly controlled
      (HbA(1c)>8%) patients with DM and 40 healthy children were included as normal
      controls. RESULTS: Levels of MDA, NO, VEGF, ICAM, apolipoprotein A1 and
      apolipoprotein B in metabolically poorly controlled diabetic patients were
      significantly higher than control group (P<0.05). In correlation analysis of
      HbA(1c) to VEGF, no significant correlations were detected in metabolically well
      controlled DM, but there were significant correlations between HbA(1c) and NO,
      MDA, ICAM levels. In correlation analysis of HbA(1c) to VEGF, NO, MDA and ICAM
      levels, significant correlations were detected in poorly controlled diabetics
      (P<0.05). CONCLUSIONS: In the present study, increased levels of MDA, NO, ICAM-1
      and VEGF levels showed that especially metabolically poorly controlled DM
      children are at high risk of atherosclerosis and vascular complications of DM and
      that there is a significant relationship between HbA(1c) and oxidative stress. It
      may be appropriate to evaluate levels of VEGF and sICAM-1 as well as markers of
      oxidative stress in addition to routine laboratory assessments in evaluation of
      type 1 DM pediatric patients.

PMID- 16442661
TI  - Plasma lipid levels and nutritional intake in childhood- and adolescence-onset
      young type 1 diabetic patients in Japan.
AB  - In recent years, the diet of the young Japanese has changed to westernized diet
      with high fat content. Childhood-onset type 1 diabetic patients have had good
      diet training since onset of the disease, but adolescence-onset type 1 diabetic
      patients have already established westernized diet habit at onset of the disease,
      which may not be easily improved. We hypothesized that a difference of the age at
      onset of the disease may affect nutritional status and plasma lipid levels in
      Japanese type 1 diabetic patients. Plasma lipid levels and nutritional intake
      were compared between childhood- and adolescence-onset young type 1 diabetic
      patients. Our research involved 9 childhood-onset type 1 diabetic patients
      (childhood group), 11 adolescence-onset type 1 diabetic patients (adolescent
      group), and 24 age-matched non-diabetic control subjects. There were no
      significant differences in age and body mass index (BMI), daily energy intake
      among the childhood group, the adolescent group, and the non-diabetic control
      group. There was no significant difference in HbA1c level between the childhood
      group and the adolescent group. The adolescent group had significantly higher
      plasma levels of total cholesterol, triglyceride, and low-density lipoprotein
      (LDL)-cholesterol than the childhood group (p<0.01, <0.05, and <0.001,
      respectively) or the control group (p<0.001, <0.001, and <00.001, respectively).
      The adolescent group had significantly lower plasma level of high-density
      lipoprotein (HDL)-cholesterol than the childhood group (p<0.05). The adolescent
      group had significantly higher percentage energy intake from fat (31.7%,
      p<0.001), higher saturated fatty acids intake (19.0g/day, p<0.01), and higher
      cholesterol intake (428mg/day, p<0.05), and significantly lower polyunsaturated
      fatty acids intake (13.4g/day, p<0.05) and lower fiber intake (9.5g/day, p<0.01)
      than the childhood group. It is concluded that young Japanese type 1 diabetic
      patients with onset of adolescence have lipid abnormalities, which may be mainly
      caused by westernized dietary habits.

PMID- 16442662
TI  - A novel mutation of WFS1 gene in a Japanese man of Wolfram syndrome with positive
      diabetes-related antibodies.
AB  - Wolfram syndrome is a rare, autosomal recessive disorder characterized by early
      onset diabetes mellitus, optic atrophy and neurological and endocrinological
      abnormalities. A 47-year-old Japanese man with frequent severe hypoglycemic
      episodes was diagnosed as Wolfram syndrome based on clinical features and
      laboratory data. He had positive glutamic acid decarboxylase (GAD) and insulinoma
      associated antigen-2 (IA-2) antibodies, both uncommon in this syndrome. Genetic
      analysis revealed that WFS1 gene of the patient has a homozygous 5 base pairs
      (AAGGC) insertion at position 1279 in exon 8, causing a frameshift at codon 371
      leading to premature termination at codon 443.

PMID- 16442663
TI  - Diagnosing duplications--can it be done?
AB  - New genes arise through duplication and modification of DNA sequences on a range
      of scales: single gene duplication, duplication of large chromosomal fragments
      and whole-genome duplication. Each duplication mechanism has specific
      characteristics that influence the fate of the resulting duplicates, such as the
      size of the duplicated fragment, the potential for dosage imbalance, the
      preservation or disruption of regulatory control and genomic context. The ability
      to diagnose or identify the mechanism that produced a pair of paralogs has the
      potential to increase our ability to reconstruct evolutionary history, to
      understand the processes that govern genome evolution and to make functional
      predictions based on paralogy. The recent availability of large amounts of whole
      genome sequence, often from several closely related species, has stimulated a
      wealth of new computational methods to diagnose gene duplications.

PMID- 16442664
TI  - G-Protein-coupled receptor-associated A-kinase anchoring proteins: AKAP79 and
      AKAP250 (gravin).
AB  - A-kinase anchoring proteins (AKAPs) define an expanding group of scaffold
      proteins that display a signature binding site for the RI/RII subunit of protein
      kinase A. AKAPs are multivalent and a subset of these scaffold proteins also
      display the ability to associate with the prototypic member of G-protein-coupled
      receptors, the beta(2)-adrenergic receptor. Both AKAP79 (also known as AKAP5) and
      AKAP250 (also known as gravin or AKAP12) have been shown to associate with the
      beta(2)-adrenergic receptor, but each directs downstream signaling events in
      decidedly different manners. The primary structures, common and unique protein
      motifs are of interest. Both proteins display largely natively unfolded primary
      sequences that provide a necklace on which short, structured regions of sequence
      are found. Membrane association appears to involve both interactions with the
      lipid bilayer via docking to a G-protein-coupled receptor as well as interactions
      of short positively charged domains with the inner leaflet of the cell membrane.
      Gravin, unlike AKAP79, displays a canonical site at its N-terminus that is
      subject to N-myristoylation. AKAP79 appears to function in switching signaling
      pathways of the receptor from adenylylcyclase to activation of the mitogen
      activated protein kinase cascade. Gravin, in contrast, is essential for the
      resensitization and recycling of the receptors following agonist-induced
      activation, desensitization, and internalization. Each AKAP provides a template
      that enables space-time continuum features to G-protein-coupled signaling
      pathways as well as a paradigm for explaining apparent compartmentalization of
      cell signaling.

PMID- 16442665
TI  - Oleosin gene family of Coffea canephora: quantitative expression analysis of five
      oleosin genes in developing and germinating coffee grain.
AB  - Coffee grains have an oil content between 10% and 16%, with these values
      associated with Coffea canephora (robusta) and C. arabica (arabica),
      respectively. As the majority of the oil stored in oil seeds is contained in
      specific structures called oil bodies, we were interested in determining whether
      there are any differences in the expression of the main oil body proteins, the
      oleosins, between the robusta and arabica varieties. Here, we present the
      isolation, characterization and quantitative expression analysis of six cDNAs
      representing five genes of the coffee oleosin family (CcOLE-1 to CcOLE-5) and one
      gene of the steroleosin family (CcSTO-1). Each coffee oleosin cDNA encodes for
      the signature structure for oleosins, a long hydrophobic central sequence
      containing a proline KNOT motif. Sequence analysis also indicates that the C
      terminal domain of CcOLE-1, CcOLE-3 and CcOLE-5 contain an 18-residue sequence
      typical of H-form oleosins. Quantitative RT-PCR showed that the transcripts of
      all five oleosins were predominantly expressed during grain maturation in robusta
      and arabica grain, with CcOLE-1 and CcOLE-2 being more highly expressed. While
      the relative expression levels of the five oleosins were similar for robusta and
      arabica, significant differences in the absolute levels of expression were found
      between the two species. Quantitative analysis of oleosin transcripts in
      germinating arabica grain generally showed that the levels of these transcripts
      were lower in the grain after drying, and then further decreased during
      germination, except for a small spike of expression for CcOLE-2 early in
      germination. In contrast, the levels of CcSTO-1 transcripts remained relatively
      constant during germination, in agreement with suggestions that this protein is
      actively involved in the process of oil body turnover. Finally, we discuss the
      implications of the coffee oleosin expression data presented relative to the
      predicted roles for the different coffee oleosins during development and
      germination.

PMID- 16442666
TI  - Determinants and predictive validity of direct and indirect measures of recently
      acquired food attitudes.
AB  - The present study examined whether the affective priming paradigm in the picture
      picture naming task can be used to measure recently acquired food attitudes. Food
      (dis)likes were induced by an evaluative learning procedure in which real food
      items were contingently paired with sensory liking or expected consequences
      information. It was found that the picture-picture naming task is capable of
      measuring recently induced food attitudes irrespective of whether they were based
      on sensory liking or expected consequences information. In addition, we observed
      that affective priming effects that are obtained with the naming task can be used
      to predict food-related choice behaviour, irrespective of whether participants
      are given time to elaborate on their choice or not. The latter finding, however,
      emerged only when food attitudes were based on sensory liking.

PMID- 16442667
TI  - Impact of nutrition messages on children's food choice: pilot study.
AB  - This pilot study tested the influence of nutrition message framing on snack
      choice among kindergarteners. Three classrooms were randomly assigned to watch
      one of the following 60s videos: (a) a gain-framed nutrition message (i.e. the
      positive benefits of eating apples) (n=14); (b) a loss-framed message (i.e. the
      negative consequences of not eating apples) (n=18); or (c) a control scene
      (children playing a game) (n=18). Following this, the children were offered a
      choice between animal crackers and an apple for their snack. Among the children
      who saw one of the nutrition message videos, 56% chose apples rather than animal
      crackers; in the control condition only 33% chose apples. This difference was
      statistically significant (chi2=7.56, p<0.01). These results suggest that videos
      containing nutritional messages may have a positive influence on children's short
      term food choices.

PMID- 16442668
TI  - Isocaloric meal and snack foods differentially affect eating behavior.
AB  - The present study tested whether foods categorized as meals reduce subsequent
      intake more than isocaloric foods categorized as snacks. The study was repeated
      three times with variations. In each variation we manipulated whether subjects
      received meal or snack foods in an isocaloric load. In Variation 1, subjects
      consumed less following a load of meal foods than snacks. Variation 2 found this
      effect to be short-term, affecting food choice 20 min following a load but not 3
      h later. Variation 3 demonstrated: (1) this effect occurs independent of the
      effects of the weights of foods, and (2) this effect varies specifically with
      subject perceptions of foods (i.e. whether they are part of a meal or snack).
      These results are discussed in terms of how cognitive representations of preload
      foods can influence subsequent consumption.

PMID- 16442669
TI  - Plasma urocortin 1 in sheep: regional sampling and effects of experimental heart
      failure.
AB  - Although urocortin 1 (Ucn-1) has been reported to circulate in human plasma and
      be raised in heart failure, little, if any, information is available regarding
      the source of circulating Ucn-1. Accordingly, we have performed trans-organ
      arteriovenous sampling for measurement of Ucn-1 concentration in anesthetized
      sheep before and after development of pacing-induced heart failure. Arterial
      plasma Ucn-1 levels measured 15.2 +/- 0.5 pmol/L in normal sheep and increased
      significantly following development of heart failure to 19.1 +/- 1.6 (p < 0.05).
      Small but significant positive arteriovenous gradients were observed across the
      hepatic and renal tissue beds in both states, with rises across the hind limb
      significant in normal animals and across the head in heart failure. This is the
      first report identifying sources of circulating Ucn-1.

PMID- 16442670
TI  - Postmortem brain fatty acid profile of levodopa-treated Parkinson disease
      patients and parkinsonian monkeys.
AB  - Fatty acids play a critical role in brain function but their specific role in the
      pathophysiology of Parkinson disease (PD) and levodopa-induced motor
      complications is still unknown. From a therapeutic standpoint, it is important to
      determine the relation between brain fatty acids and PD because the brain fatty
      acid content depends on nutritional intake, a readily manipulable environmental
      factor. Here, we report a postmortem analysis of fatty acid profile by gas
      chromatography in the brain cortex of human patients (12 PD patients and nine
      Controls) as well as in the brain cortex of monkeys (four controls, five drug
      naive MPTP monkeys and seven levodopa-treated MPTP monkeys). Brain fatty acid
      profile of cerebral cortex tissue was similar between PD patients and Controls
      and was not correlated with age of death, delay to autopsy or brain pH. Levodopa
      administration in MPTP monkeys increased arachidonic acid content (+7%; P < 0
      .05) but decreased docosahexaenoic acid concentration (-15%; P < 0.05) and total
      n-3:n-6 polyunsaturated fatty acids ratio (-27%; P < 0.01) compared to drug-naive
      MPTP animals. Interestingly, PD patients who experienced motor complications to
      levodopa had higher arachidonic acid concentrations in the cortex compared to
      Controls (+13.6%; P < 0.05) and to levodopa-treated PD patients devoid of motor
      complications (+14.4%; P < 0.05). Furthermore, PD patients who took an above
      median cumulative dose of levodopa had a higher relative amount of saturated
      fatty acids but lower monounsaturated fatty acids in their brain cortex (P <
      0.01). These results suggest that changes in brain fatty acid relative
      concentrations are associated with levodopa treatment in PD patients and in a non
      human primate model of parkinsonism.

PMID- 16442671
TI  - Iron accumulation in the striatum predicts aging-related decline in motor
      function in rhesus monkeys.
AB  - Changes in the nigrostriatal system may be involved with the motor abnormalities
      seen in aging. These perturbations include alterations in dopamine (DA) release,
      regulation and transport in the striatum and substantia nigra, striatal atrophy
      and elevated iron levels in the basal ganglia. However, the relative contribution
      of these changes to the motor deficits seen in aging is unclear. Thus, using the
      rhesus monkey as a model, the present study was designed to examine several of
      these key alterations in the basal ganglia in order to help elucidate the
      mechanisms contributing to age-related motor decline. First, 32 female rhesus
      monkeys ranging from 4 to 32 years old were evaluated for their motor
      capabilities using an automated hand-retrieval task. Second, non-invasive MRI
      methods were used to estimate brain composition and to indirectly measure
      relative iron content in the striatum and substantia nigra. Third, in vivo
      microdialysis was used to evaluate basal and stimulus-evoked levels of DA and its
      metabolites in the striatum and substantia nigra of the same monkeys. Our results
      demonstrated significant decreases in motor performance, decreases in striatal DA
      release, and increases in striatal iron levels in rhesus monkeys as they age from
      young adulthood. A comprehensive statistical analysis relating age, motor
      performance, DA release, and iron content indicated that the best predictor of
      decreases in motor ability, above and beyond levels of performance that could be
      explained by age alone, was iron accumulation in the striatum. This suggests that
      striatal iron levels may be a biomarker of motor dysfunction in aging; and as
      such, can be monitored non-invasively by longitudinal brain MRI scans. The
      results also suggest that treatments aimed at reducing accumulation of excess
      iron in the striatum during normal aging may have beneficial effects on age
      related deterioration of motor performance.

PMID- 16442672
TI  - The effect of problem-based learning on students' approaches to learning in the
      context of clinical nursing education.
AB  - The effect of problem-based learning (PBL) on nursing students' approaches to
      learning has received scanty attention in nursing education. The purpose of the
      present study was to evaluate the effect of PBL on students' approaches to
      learning in clinical nursing education. Using a one-group before-after quasi
      experimental design, the revised two-factor Study Process Questionnaire (R-SPQ
      2F) was administered to compare students' approaches to learning before and after
      a period of clinical education in which PBL was implemented. Focus group
      interviews were used to elicit from students their PBL experience. Of the 237
      students who participated in the study, 187 returned the R-SPQ-2F, representing a
      response rate of 78.9%. Twenty-eight of the students also participated in focus
      group interviews. The R-SPQ-2F scores indicated that for the deep approach to
      learning, the post-test mean score was noticeably higher than that at the pre
      test (p=0.005). No significant difference was observed between the pre-test and
      post-test mean scores for the surface approach to learning (p>or=0.05). The four
      themes inductively derived from students' descriptions of their clinical
      education experience (motivated to learn; self-direction in learning; active,
      interactive and student-centred learning; and enjoyment in learning) also
      suggested that the students adopted a deep approach to learning during a period
      of clinical education in which PBL was implemented.

PMID- 16442673
TI  - Plant-made subunit vaccine against pneumonic and bubonic plague is orally
      immunogenic in mice.
AB  - Yersinia pestis, the causative agent of plague, is an extremely virulent
      bacterium but there are no approved vaccines for protection against it. Our goal
      was to produce a vaccine that would address: ease of delivery, mucosal efficacy,
      safety, rapid scalability, and cost. We developed a novel production and delivery
      system for a plague vaccine of a Y. pestis F1-V antigen fusion protein expressed
      in tomato. Immunogenicity of the F1-V transgenic tomatoes was confirmed in mice
      that were primed subcutaneously with bacterially-produced F1-V and boosted orally
      with transgenic tomato fruit. Expression of the plague antigens in fruit allowed
      producing an oral vaccine candidate without protein purification and with minimal
      processing technology.

PMID- 16442675
TI  - Note on the anatomical condition affecting the underside of the wrist not
      previously reported. 1861.

PMID- 16442674
TI  - Application of SO(4)(2-)/TiO2 solid superacid in decontaminating radioactive
      pollutants.
AB  - Polyaniline doped with SO(4)(2-)/TiO(2) superacid shows good conductive ability.
      When used in a strippable coating film for decontaminating radioactive
      pollutants, the SO(4)(2-)/TiO(2) solid superacid replacing HCl exhibits higher
      electrical conductivity (7.01 s/cm) and a decontamination ratio higher than 97%.
      Coating and electrolyzing the film in solution or in dry medium were effective
      methods, the latter was more promising for decontaminating radioactive pollutants
      which were attached to the surface or within the body of equipments used in
      nuclear industry.

PMID- 16442676
TI  - Force-plate based computation of ankle and hip strategies from double-inverted
      pendulum model.
AB  - BACKGROUND: Using statistical characteristics of the centre of pressure
      displacement or of the ground reaction forces, it is difficult to have
      quantitative evaluation of the equilibrium strategy employed (ankle or hip). The
      purpose of this study is to validate a new force-plate based approach that allows
      to evaluate postural strategies employed through a method based on a double
      inverted pendulum model. METHODS: This method allows to compute ankle and hip
      joint motion only from force plate data and relies on inverse kinematics with the
      centre of mass considered as the end effector. Furthermore, an index, depending
      on the covariance between hip and ankle angles, is proposed to quantify the
      strategy used. To validate the method and the strategy index, we compare the
      results of our computation to an optical stereophotogrammetry measurement of the
      angles considered as reference value. FINDINGS: The experiments demonstrate that
      our method provides acceptable results. The root mean square error between
      computed and measured hip and ankle angles stands between 4.5 x 10(-3)degrees for
      ankle angle in static condition and 1.1 x 10(-1) degrees for hip angle in hip
      forced condition. INTERPRETATION: The main interest of our method for clinicians
      is that it allows to retrieve the ankle and hip angles only using a simple and
      widespread device, the force-plate. Moreover, it proposes a new postural index
      that can be also be computed without videographic systems.

PMID- 16442677
TI  - Effects of different levels of torso coactivation on trunk muscular and kinematic
      responses to posteriorly applied sudden loads.
AB  - BACKGROUND: Studies examining rapid spine loading have documented the influence
      of steady-state trunk preloads, and the resulting levels of trunk muscle
      preactivation, on the control of spine stability. However, the effects of
      different levels of muscle coactivation, and resulting spine loads, on the
      response to a perturbation of the externally unloaded trunk are unclear. METHODS:
      Fourteen male subjects coactivated the abdominal muscles at four different levels
      (approximately 0%, 10%, 20% and 30% of the maximal voluntary contraction)
      monitored by an electromyography biofeedback system while semi-seated in a
      neutral lumbar spine position. They were loaded posteriorly in two directions (0
      degrees and 30 degrees from the sagittal plane) and with two different loads
      (6.80 and 9.07 kg). Force perturbation, spine displacement and electromyography
      activity were measured, and torso compression and stability were modeled.
      FINDINGS: Abdominal coactivation significantly increased spine stability and
      reduced the movement of the lumbar spine after perturbation, but at the cost of
      increasing spinal compression. Preactivation also reduced the frequency and
      magnitude, and delayed the onset of muscle reactions, mainly for the back muscles
      and the internal oblique. The higher magnitude load and the load applied in an
      oblique direction both showed more potentially hazardous effects on the trunk.
      INTERPRETATION: Torso coactivation increases spinal stiffness and stability and
      reduces the necessity for sophisticated muscle responses to perturbation.
      Although further investigation is needed, it appears there is an asymptotic
      function between coactivation and both stiffness and stability. There also
      appears to be more hazard when buttressing twisting components of a sudden load
      compared to sagittal components. Patients with trunk instability and intolerance
      to spine compression may benefit from low to moderate levels of coactivation.

PMID- 16442678
TI  - In vitro fixator rod loading after transforaminal compared to anterior lumbar
      interbody fusion.
AB  - BACKGROUND: Cages are commonly used to assist lumbar interbody fusion. They are
      implanted from various approaches. In many cases internal fixators are added to
      provide sufficient stability. However, how the rods of these fixators are loaded
      and whether the kind of approach affects these loads is still unknown. The aim of
      this in vitro study therefore was to determine the loads acting on fixator rods
      and cages after anterior compared to transforaminal lumbar interbody fusion.
      METHODS: Six intact human lumbar spine specimens (L1-5) were loaded in a spine
      tester with pure moments (+/-7.5 N m) in the frontal, sagittal and transverse
      plane. Loading was repeated, first, after the segments L2-3 and L4-5 were
      instrumented either with an anterior or a transforaminal lumbar interbody fusion
      cage "stand alone" and, second, after additional stabilisation with an internal
      fixator. The rods of the fixator and the four "corners" of the cages were
      instrumented with strain gauges. FINDINGS: The loads transmitted through the rods
      were highest in lateral bending. In this loading direction an axial distraction
      force of in median up to 140 N, an axial compression force of up to 100 N, and a
      resultant bending moment of up to 1.1 N m were measured in each rod. These loads
      tended to be lower for the anterior compared to the transforaminal approach. For
      comparison, the load applied was +/-7.5 N m. The axial strains recorded in the
      four "corners" of the cages considerably varied from one specimen to the other.
      Differences in cage strain between the two approaches could not be detected.
      INTERPRETATION: The loads acting on the rods of the fixator were small compared
      to the load that was applied. Thus, other structures such as the cages or the
      facet joints still play an important role in load transfer. The type of approach
      (anterior or transforaminal) had only little effect on the loading of the rods.
      This also applies to the local loading of the cages, which probably more depends
      on the fit between cage and endplates and on the local stiffness properties of
      the adjacent vertebral bodies.

PMID- 16442679
TI  - Antiphospholipid syndrome: an evolving story.
AB  - Antiphospholipid Syndrome (APS) is a form of immune mediated thrombophilia,
      presenting as recurrent thrombotic events and pregnancy morbidity, in association
      with positive laboratory tests for antiphospholipid antibodies (APA) in the form
      of Lupus Anticoagulant (LA) or anticardiolipin antibodies(ACA). Insights into the
      pathophysiology of the condition suggest that some antibodies are prothrombotic
      in vivo, and that the mechanism of thrombosis is likely to be multifactorial. APS
      has a broad spectrum of clinical presentations, and the laboratory diagnosis can
      be difficult due to heterogeneity of APAs and poor standardisation of laboratory
      tests. Anticoagulation is the mainstay of the management of the thrombotic and
      obstetric complications of APS. The risk of recurrent thrombosis appears to be
      high, and the duration and intensity of therapy remains controversial. Randomised
      controlled trials have shown that standard intensity anticoagulation is adequate
      in most cases of venous thrombosis. Further trials are required to establish
      whether high intensity coagulation is of benefit in recurrent or arterial
      thrombosis. The optimal management of recurrent fetal loss is debated and large
      studies are required to establish a clear benefit of heparin and aspirin over
      aspirin alone or supportive care.

PMID- 16442680
TI  - Procedures of trophic chain samples preparation for determination of triazines by
      HPLC and metals by ICP-AES methods.
AB  - The aim of this research was monitoring the distribution of atrazine and simazine
      as well as metals Pb, Cd, Zn, Al, Co, Ni, and V along with trophic chains: soil
      vegetables and soil, carrot or grass and meat. Different techniques of herbicides
      extraction by means of many solvents were examined. Triazines were analysed by
      means of HPLC, metals by means of ICP-AES. Detection limits: LOD=0.2 microg ml(
      1), determination limits: LOQ=0.73 microg ml(-1) for atrazine and LOD=0.3 microg
      ml(-1), LOQ=1.12 microg ml(-1) for simazine were obtained. The content (microg g(
      1)) of simazine in soil was in range: 3.45-8.60, in vegetable roots: 6.62-38.15,
      in vegetable leaves: 2.45-31.71, in rabbit fat: 0.13-49.90. The content (microg
      g(-1)) of atrazine in soils was in range: 11.9-13.03, in vegetable roots: 13.61
      92.90. In analysed material the particular metals after microwave or dry
      digestion were determined in range (microg g(-1)): Pb: 6.48-43.18; Cd: 0.11-0.57;
      Zn: 8.79-51.90; Al: 10.22-24.48; Co: 0.18-3.89; Ni: 0.37-6.36; V: 0.29-1.48.

PMID- 16442681
TI  - Detection of copper(II) and zinc(II) binding to humic acids from pig slurry and
      amended soils by fluorescence spectroscopy.
AB  - The effect of the consecutive annual additions of pig slurry at rates of 0
      (control), 90 and 150 m3 ha(-1) yr(-1) after a 7-year period on the Cu(II) and
      Zn(II) binding behavior of soil HAs was investigated in a field experiment. A
      fluorescence titration method and a single site model were used for determining
      metal ion complexing capacities and stability constants of metal ion complexes of
      HAs isolated from pig slurry and unamended and amended soils. With respect to
      control soil HA, pig-slurry HA featured much smaller Cu(II) and Zn(II) binding
      capacities and stability constants. Pig-slurry application to soil decreased
      Cu(II) and Zn(II) complexing capacities and binding affinities of soil HA. These
      effects increased with increasing the rate per year of PS application to soil,
      and are expected to have a large impact on bioavailability, mobilization, and
      transport of Cu(II) and Zn(II) ions in pig slurry-amended soils.

PMID- 16442682
TI  - Morphological and cytological responses of ammonia (foraminifera) to copper
      contamination: implication for the use of foraminifera as bioindicators of
      pollution.
AB  - The effect of graded concentrations of copper was analyzed at morphological and
      cytological levels on two species of Ammonia (foraminifera) often found in
      polluted areas. The two species were sensitive to low concentration, but survived
      high concentration (threshold value<10 microg l(-1), lethal value>200 microg l(
      1)), which gives them a high potential value as bioindicators. Increasing
      concentrations lead to (1) increasing delay before production of new chambers,
      explaining dwarfism in polluted areas; (2) increasing delay before reproduction
      and decreasing number of juveniles, explaining low density; and (3) increasing
      proportion of deformed tests. Cytological modifications occurred only in deformed
      specimens (thickening of the organic lining, proliferation of fibrillar and of
      large lipidic vesicles, increased number of residual bodies). They may be
      responsible for anomalies in biomineralization processes. The detection of sulfur
      in deformed specimens suggests that foraminifers may have a detoxification
      mechanism with production of a metallothionein-like protein.

PMID- 16442683
TI  - Arsenic chemistry in the rhizosphere of Pteris vittata L. and Nephrolepis
      exaltata L.
AB  - This greenhouse experiment evaluated the influence of arsenic uptake by arsenic
      hyperaccumulator Pteris vittata L. and non-arsenic hyperaccumulator Nephrolepis
      exaltata L. on arsenic chemistry in bulk and rhizosphere soil. The plants were
      grown for 8 weeks in a rhizopot with a soil containing 105 mg kg(-1) arsenic. The
      soil arsenic was fractionated into five fractions with decreasing availability:
      non-specifically bound (N), specifically bound (S), amorphous hydrous-oxide bound
      (A), crystalline hydrous-oxide bound (C), and residual (R). P. vittata produced
      larger plant biomass (7.38 vs. 2.32 mg plant(-1)) and removed more arsenic (2.61
      vs. 0.09 mg pot(-1) arsenic) than N. exaltata. Plant growth reduced water-soluble
      arsenic, and increased soil pH (P. vittata only) in the rhizosphere soil. P.
      vittata was more efficient than N. exaltata to access arsenic from all fractions
      (39-64% vs. 5-39% reduction). However, most of the arsenic taken up by both
      plants was from the A fraction (67-77%) in the rhizosphere soil, the most
      abundant (61.5%) instead of the most available (N fraction).

PMID- 16442684
TI  - Revised assessment of cancer risk to dichloromethane: part I Bayesian PBPK and
      dose-response modeling in mice.
AB  - The current USEPA cancer risk assessment for dichloromethane (DCM) is based on
      deterministic physiologically based pharmacokinetic (PBPK) modeling involving
      comparative metabolism of DCM by the GST pathway in the lung and liver of humans
      and mice. Recent advances in PBPK modeling include probabilistic methods and, in
      particular, Bayesian inference to quantitatively address variability and
      uncertainty separately. Although Bayesian analysis of human PBPK models has been
      published, no such efforts have been reported specifically addressing the mouse,
      apart from results included in the OSHA final rule on DCM. Certain aspects of the
      OSHA model, however, are not consistent with current approaches or with the
      USEPA's current DCM cancer risk assessment. Therefore, Bayesian analysis of the
      mouse PBPK model and dose-response modeling was undertaken to support development
      of an improved cancer risk assessment for DCM. A hierarchical population model
      was developed and prior parameter distributions were selected to reflect
      parameter values that were considered the most appropriate and best available.
      Bayesian modeling was conducted using MCSim, a publicly available software
      program for Markov Chain Monte Carlo analysis. Mean posterior values from the
      calibrated model were used to develop internal dose metrics, i.e., mg DCM
      metabolized by the GST pathway/L tissue/day in the lung and liver using exposure
      concentrations and results from the NTP mouse bioassay, consistent with the
      approach used by the USEPA for its current DCM cancer risk assessment. Internal
      dose metrics were 3- to 4-fold higher than those that support the current USEPA
      IRIS assessment. A decrease of similar magnitude was also noted in dose-response
      modeling results. These results show that the Bayesian PBPK model in the mouse
      provides an improved basis for a cancer risk assessment of DCM.

PMID- 16442685
TI  - Lamotrigine-associated anticonvulsant hypersensitivity syndrome in bipolar
      disorder.
AB  - Anticonvulsant hypersensitivity syndrome (AHS) is a rare but life-threatening
      adverse effect of aromatic anticonvulsants such as phenytoin, phenobarbital and
      carbamazepine, although there is extensive experience with AHS related to these
      anticonvulsants. Very few cases of lamotrigine-associated AHS have been reported
      in bipolar patients and most reported cases were published in non-psychiatric
      journals. The authors describe here the occurrence of an AHS in a 48-year-old
      bipolar woman who was treated with lamotrigine, valproic acid and venlafaxine for
      her depressive symptoms. She developed a high fever, generalized maculopapular
      rash, pancytopenia, pneumonitis and hepatitis after we added lamotrigine to
      valproate and venlafaxine. These adverse drug reactions resolved after the
      discontinuation of lamotrigine and valproate, and the administration of oral
      antihistamine and corticosteroid. Our case demonstrates that the most important
      steps in the management of lamotrigine-associated AHS are to recognize the
      disorder, discontinue the offending anticonvulsants, provide supportive care in
      an inpatient setting, and treat with antihistamine and steroids when appropriate.

PMID- 16442686
TI  - Academic psychiatry and the pharmaceutical industry.
AB  - In the second half of the 19th century new drugs introduced by the pharmaceutical
      industry helped lead to the establishment of academic departments in psychiatry.
      Causal treatment of cerebral pellagra by nicotinic acid and cerebral syphilis by
      penicillin in the first half of the 20th century led to major changes in the
      diagnostic distribution of psychiatric patients. In the second half of the 20th
      century with the introduction of a rapidly growing number of psychotropic drugs,
      pharmacotherapy became the primary form of treatment in mental illness.
      Psychiatrists today perceive neuropharmacology as one of the basic sciences of
      psychiatry and psychopharmacology as the bridge between the mode of action and
      the clinical indications of psychotropic drugs. Pharmacotherapy with psychotropic
      drugs focused attention on the differential responsiveness to the same drug
      within the same diagnostic category. Yet, instead of re-evaluating psychiatric
      nosology and conducting research in psychopathology, a statistical methodology
      was adopted for the demonstration of therapeutic effectiveness in
      pharmacologically heterogeneous populations. Employment of consensus-based
      classifications and psychiatric rating scales in the clinical development of
      psychotropic drugs led to semi-finished products, which are prescribed
      indiscriminately. Replacement of single-center clinical trials by multi-center
      centrally coordinated clinical investigations led to the control of education in
      pharmacotherapy by the pharmaceutical industry. To separate education from
      marketing, the identification of the treatment-responsive forms of illness and
      the delineation of the therapeutic profile of psychotropic drugs are proposed
      with the employment of a new methodology, the "Composite Diagnostic Evaluation
      System." It is postulated that development of a pharmacologically valid
      psychiatric nosology with the employment of a "nosologic matrix" would provide
      the pharmaceutical industry with the necessary feedback to develop clinically
      selective drugs in mental illness and to break the impasse of progress in
      "translational research" in psychiatry.

PMID- 16442687
TI  - Lack of chemopreventive effects of ginger on colon carcinogenesis induced by 1,2
      dimethylhydrazine in rats.
AB  - Ginger (Zingiber officinale Roscoe) has been proposed as a promising candidate
      for cancer prevention. Its modifying potential on the process of colon
      carcinogenesis induced by 1,2-dimethylhydrazine (DMH) was investigated in male
      Wistar rats using the aberrant crypt foci (ACF) assay. Five groups were studied:
      Groups 1-3 were given four s.c. injections of DMH (40 mg/kg b.w.) twice a week,
      during two weeks, whereas Groups 4 and 5 received similar injections of EDTA
      solution (DMH vehicle). After DMH-initiation, the animals were fed a ginger
      extract mixed in the basal diet at 0.5% (Group 2) and 1.0% (Groups 3 and 4) for
      10 weeks. All rats were killed after 12 weeks and the colons were analyzed for
      ACF formation and crypt multiplicity. The rates of cell proliferation and
      apoptosis were also evaluated in epithelial colonic crypt cells. Dietary
      consumption of ginger at both dose levels did not induce any toxicity in the
      rats, but ginger meal at 1% decreased significantly serum cholesterol levels
      (p<0.038). Treatment with ginger did not suppress ACF formation or the number of
      crypts per ACF in the DMH-treated group. Dietary ginger did not significantly
      change the proliferative or apoptosis indexes of the colonic crypt cells induced
      by DMH. Thus, the present results did not confirm a chemopreventive activity of
      ginger on colon carcinogenesis as analyzed by the ACF bioassay and by the growth
      kinetics of the colonic mucosa.

PMID- 16442688
TI  - Molecular biomarkers of oxidative stress associated with bromate carcinogenicity.
AB  - Potassium bromate (KBrO3) is a chemical oxidizing agent found in drinking water
      as a disinfection byproduct of surface water ozonation. Chronic exposures to
      KBrO3 cause renal cell tumors in rats, hamsters and mice and thyroid and
      testicular mesothelial tumors in rats. Experimental evidence indicates that
      bromate mediates toxicological effects via the induction of oxidative stress. To
      investigate the contribution of oxidative stress in KBrO3-induced cancer, male
      F344 rats were administered KBrO3 in their drinking water at multiple
      concentrations for 2-100 weeks. Gene expression analyses were performed on
      kidney, thyroid and mesothelial cell RNA. Families of mRNA transcripts
      differentially expressed with respect to bromate treatment included multiple
      cancer, cell death, ion transport and oxidative stress genes. Multiple
      glutathione metabolism genes were up-regulated in kidney following carcinogenic
      (400 mg/L) but not non-carcinogenic (20 mg/L) bromate exposures. 8
      Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate
      treatment in kidney but not thyroid. A dramatic decrease in global gene
      expression changes was observed following 1mg/L compared to 20 mg/L bromate
      exposures. In a separate study oxygen-18 (18O) labeled KBrO3 was administered to
      male rats by oral gavage and tissues were analyzed for 18O deposition. Tissue
      enrichment of 18O was observed at 5 and 24 h post-KBr18O3 exposure with the
      highest enrichment occurring in the liver followed by the kidney, thyroid and
      testes. The kidney dose response observed was biphasic showing similar
      statistical increases in 18O deposition between 0.25 and 50 mg/L (equivalent
      dose) KBr18O3 followed by a much greater increase above 50 mg/L. These results
      suggest that carcinogenic doses of potassium bromate require attainment of a
      threshold at which oxidation of tissues occurs and that gene expression profiles
      may be predictive of these physiological changes in renal homeostasis.

PMID- 16442689
TI  - Oxidative damages in the DNA, lipids, and proteins of rats exposed to isofluranes
      and alcohols.
AB  - DNA damage, lipid peroxidation and protein oxidation were evaluated in rats
      exposed to a 1% isoflurane atmosphere with or without alcohol administration
      (administrated by gastric intubation at 4 g/kg body weight as a 50% solution).
      Single cell gel electrophoresis assays were performed in order to evaluate DNA
      damage occurring in the lymphocytes, spleen, bone marrow, brain, livers and lung
      of rats exposed to 1% isoflurane for 30 or 60 min with/without ethanol. Levels of
      malondialdehydes (MDA), a metabolite of lipid peroxidation, were determined in
      plasma and tissues. Carbonyl contents were also analyzed to determine levels of
      protein oxidation in plasma and tissues. Levels of DNA damage in lymphocytes,
      bone marrow, and the organ tissues of rats exposed to isoflurane were found to
      increase time dependently, and alcohol increased DNA damage. Lipid peroxidation
      and protein oxidation results showed patterns that differed from those of DNA
      damage. Levels of MDA in plasma, bone marrow, spleen, and the livers of rats
      exposed to isoflurane with/without ethanol were found to be time dependently
      increased, but this was not observed in the brain or lung. However, protein
      oxidation levels were significantly increased in the plasma, brains, and lungs of
      rats exposed to isoflurane, and exposure to isoflurane and alcohol, significantly
      increased these levels in plasma and brain. The present study demonstrates that
      isoflurane exposure results in significant DNA damage in rat lymphocytes, bone
      marrow, spleen, brain, livers, and lung. Moreover, alcohol was found to be as a
      strong inducer of DNA damage, lipid peroxidation and protein oxidation. However,
      no evidence in association between DNA damage, lipid peroxidation and protein
      oxidation was found. Regarding the effects of isoflurane and alcohol on oxidative
      damages, single strand DNA damages may be a useful biomarkers and blood cells and
      plasma appear to be more sensitive targets to oxidative damage than other
      tissues.

PMID- 16442690
TI  - Three-dimensional analysis of pulp chambers in maxillary second deciduous molars.
AB  - OBJECTIVE: The purpose of this study was to clarify the positional relationship
      between the crown contour and the pulp chamber using micro-CT system for
      restorations of maxillary second deciduous molar. METHODS: Five maxillary second
      deciduous molar teeth each from the deciduous dentition and the mixed dentition
      periods were used. The positional relationship between the crown contour and pulp
      chamber was three-dimensionally observed by micro-CT. In addition, the thickness
      of the dentin at each of the pulp horns and the volume ratio of the pulp chamber
      against the whole crown were measured. RESULTS: In relationship to the crown
      contour and the pulp chamber, the pulp horn of the mesiobuccal cusp showed
      greatest protrusion and eminent swelling of its mesial wall in both the deciduous
      dentition and the mixed dentition periods. Furthermore, the pulp chamber was
      shifted to the mesial side. The volume ratio of the pulp chamber to the whole
      crown, the ratio in the mixed dentition period showed to be significantly smaller
      than in the deciduous dentition period. The dentin thickness at the mesiobuccal
      pulp horn was the thinest. CONCLUSIONS: These results suggest that in preparation
      of cavities in maxillary second deciduous molars, care is necessary not to expose
      of the mesiobuccal pulp horn. Especially, the mesial wall of the mesiobuccal pulp
      horn should be noted.

PMID- 16442691
TI  - Deficient adjustment of cerebral blood flow to cognitive activity due to
      chronically low blood pressure.
AB  - The present study aimed to investigate aberrances in the adjustment of cerebral
      blood flow to cognitive activity due to chronically low blood pressure. By means
      of transcranial Doppler sonography blood flow velocities in both middle cerebral
      arteries (MCA) were recorded during the execution of a serial subtraction task in
      40 subjects with constitutional hypotension and 40 normotensive control persons.
      Additionally, blood pressure was continuously monitored. As a main result
      significant correlations between the task-induced changes in blood pressure and
      those in MCA blood flow velocities were found in hypotensives, but not in control
      subjects. The dependence of the regulation of cerebral blood flow on blood
      pressure points towards deficits in cerebral autoregulation in hypotension. Over
      the total sample the extent of the task-induced MCA flow velocity increase was
      positively related to cognitive performance. This underlines the importance of
      the adjustment of cerebral blood flow to current demands for optimal cognitive
      functioning.

PMID- 16442692
TI  - Population-based case-control study of allergic rhinitis during pregnancy for
      birth outcomes.
AB  - OBJECTIVE: Allergic rhinitis is frequent in women of childbearing age including
      pregnancy. The present study aimed to estimate the effect of maternal allergic
      rhinitis on birth outcomes, in particular congenital abnormalities, preterm birth
      and low birthweight newborns. STUDY DESIGN: Analysis of the population-based data
      of the Hungarian Case-Control Surveillance of Congenital Abnormalities between
      1980 and 1996. RESULTS: The evaluation of data did not reveal any teratogenic
      potential of allergic rhinitis and indeed a lower prevalence of total congenital
      abnormalities was found. In addition, a protective effect could be observed for
      preterm birth due to longer gestational age (adjusted t=2.97, p=0.003).
      CONCLUSION: Allergic rhinitis is not risk factor for pregnant women.

PMID- 16442694
TI  - Ovarian reserve in patients with autoimmune diseases.

PMID- 16442693
TI  - Proliferative activity of early ovarian clear cell adenocarcinoma depends on
      association with endometriosis.
AB  - OBJECTIVE: To investigate differences in the biological characteristics of
      ovarian clear cell adenocarcinoma based on the presence/absence of endometriosis
      and tumor proliferative activity. METHODS: Stage I ovarian clear cell
      adenocarcinoma patients were divided into groups with and without endometriosis,
      and immunohistochemical expression of proliferating cell nuclear antigen was
      determined in surgical specimens. Then xenograft models of human ovarian clear
      cell adenocarcinoma with or without human ectopic endometrium were created in
      severe combined immunodeficiency mice, and tumor growth was assessed from the wet
      weight and the bromodeoxyuridine uptake. Furthermore, a xenograft model of human
      endometriosis was made with or without ovarian clear cell adenocarcinoma and
      cytokine production was investigated. RESULTS: The proliferating cell nuclear
      antigen labeling index was significantly lower in the tumors of patients with
      endometriosis compared to the tumors of patients without endometriosis. In tumor
      bearing mice, the tumor weight and bromodeoxyuridine uptake were both
      significantly lower when ovarian clear cell adenocarcinoma was associated with
      endometriosis than in its absence. Release of transforming growth factor-beta1
      and interleukin-6 from the ectopic human endometrium was greater in the presence
      of clear cell adenocarcinoma than without it, and transforming growth factor
      beta1 levels showed a significant difference. CONCLUSION: The proliferative
      activity of early ovarian clear cell adenocarcinoma seems to depend on the
      association of this cancer with endometriosis. When endometriosis is associated
      with ovarian clear cell adenocarcinoma, there is a change of its cytokine
      production that may inhibit tumor growth.

PMID- 16442695
TI  - Lectin binding in the umbilical cord in altered glycemia.
AB  - OBJECTIVE: Content and distribution of the oligosaccharides in the umbilical cord
      from pregnancies with altered glycemia were investigated. STUDY DESIGN: A
      prospective cohort study was conducted in the Florence Policlinic of Careggi,
      Italy. Samples of cord from physiological pregnancies (n=20), from pregnancies
      with minor degree of glucose intolerance (n=20) and from pregnancies with
      gestational diabetes mellitus (GDM) treated with insulin (n=20) were collected.
      Eleven lectins were used (ConA, WGA, PNA, SBA, DBA, LTA, UEA I, OOA, GSL II, MAL
      II and SNA) in combination with chemical and enzymatic treatments. RESULTS:
      Increase of N-acetyl-d-glucosamine and a loss of sialic acid in the umbilical
      cord of the cases with minor degree of glucose intolerance with respect to the
      other study groups was observed. d-Galactose(beta1-->3)-N-acetyl-d-galactosamine,
      N-acetyl-d-galactosamine and l-fucose were in less amount in both the
      pathological groups with respect to the control one. CONCLUSION: The increase of
      some glycoconjugates carbohydrates and the loss of others in the umbilical cord
      from pregnancies with minor degree of glucose intolerance might be related to its
      morphofunctional alterations in a not diabetic altered glycemia. Moreover, the
      treatment with insulin in the GDM might play a role in restoring partially the
      normal glycosilation in the cord components in the attempt to renew some their
      functions.

PMID- 16442696
TI  - Salt-dependent binding of iron(II) mixed-ligand complexes containing 1,10
      phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine to calf thymus DNA.
AB  - The salt-dependent binding of racemic iron(II) mixed-ligand complex containing
      1,10-phenanthroline (phen) and dipyrido[3,2-a:2',3'-c]phenazine (dppz),
      [Fe(phen)2(dppz)]2+ to calf thymus DNA (ct-DNA) has been characterized by UV-VIS
      spectrophotometric titration. The equilibrium binding constant (Kb) of the
      iron(II) complex to ct-DNA decreases with the salt concentration in the solution.
      The slope, SK=(deltalog Kb/deltalog [Na2+]) has been found to be 0.49, suggesting
      that, in addition to intercalation, considerable electrostatic interaction is
      also involved in the ct-DNA binding of [Fe(phen)2(dppz)]2+. The calculation of
      non-electrostatic binding constant (Kt(o)) based on polyelectrolyte theory has
      revealed that the non-electrostatic contribution to the total binding constant
      (Kb) increases significantly with the increase in [Na+] and reaches 36% at 0.1 M
      NaCl. On the other hand, the contribution of the non-electrostatic binding free
      energy (DeltaGt(o)) to the total binding free energy change (DeltaGo) is
      considerably large, i.e. 87% at [Na+]=0.1 M, suggesting that the stabilization of
      the DNA binding is mostly due to the contribution of non-electrostatic process.
      Moreover, the effect of specific ligand substitutions on DeltaGo has been
      rigorously evaluated using the quantity DeltaDeltaGt(o), i.e. the difference in
      DeltaGt(o) relative to that of the parent iron(II) complex, [Fe(phen)3]2+,
      indicating that each substitution of phen by dip and dppz contributes 7.5 and
      17.5 kJ mol(-1), respectively to more favorable ct-DNA binding.

PMID- 16442697
TI  - Stochastic transcription initiation: Time dependent transcription rates.
AB  - The noise in the central process such as transcription, replication and
      translation of the genomic DNA is very important since it can directly affect the
      phenotypic and behavioral aspects of an organism as well as the entire cellular
      function. Here we develop a model on the transcription process based on the
      assumption that the initiation of the transcription is a stochastic event and the
      transcription rates may be time dependent random quantities. We derive the
      central measure properties i.e. mean and the variance, of the distribution of the
      transcription rates. Our results show that the Fano factor which is a measure of
      deviation from the Poisson distribution associated with the fluctuations in the
      number of mRNA molecules deviates from unity due to the randomness in the
      transcription rates. However when the RNA polymerase molecule searches for the
      promoter sequences on the DNA lattice by random jumps, the Fano factor approaches
      the Poisson limit as the jump size associated with the RNA polymerase increases.
      Since the jump size associated with dynamics of RNAP molecule is positively
      correlated with the degree of super coiling of DNA, we argue that the super
      coiled or close-packed structure of DNA might have evolved to keep the noises at
      the transcriptional level in a minimum.

PMID- 16442698
TI  - Reversible reaction of 5,5'-dithiobis(2-nitrobenzoate) with the CysF9[93]beta
      sulfhydryl groups of the hemoglobins of the domestic cat: variation of the
      equilibrium and reverse rate constants with pH.
AB  - We have determined for the first time the equilibrium constant, Keq, for the
      reaction of Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoate), with the
      CysF9[93]beta sulfhydryl groups of the hemoglobins of the domestic cat. In the pH
      range 5.6 to 9.0 Kequ varies over four orders of magnitude--between ca 10 and 10(
      3)--for all hemoglobin derivatives. Using these Kequ values and published data on
      the dependence of the apparent second order forward rate constant, kf, on pH we
      have calculated the apparent second order reverse rate constant, kr, as a
      function of pH. This parameter increases strongly with pH, particularly above pH
      7.5. Quantitative analyses of the pH dependence profiles of log10kr indicate that
      the reverse reaction is coupled to the ionization of two groups on the protein
      with pKas of 7.2+/-0.2 and 9.4+/-0.1 in the major hemoglobin and 6.7+/-0.3 and
      8.4+/-0.1 in the minor hemoglobin.

PMID- 16442699
TI  - Working capacity and well-being after radical cystectomy with continent cutaneous
      diversion.
AB  - OBJECTIVES: The primary aim was to compare the working capacity in patients with
      continent urinary diversion with a control group. Secondary aims were to assess
      the changes in electrolyte and acid-base homeostasis and the functional status
      during strenuous physical activity, and finally, the well-being in the two
      groups. METHODS: Eleven patients who had undergone radical cystectomy and
      continent cutaneous diversion using an ileocolonic segment participated. The
      control group consisted of 12 men, matched for age and activity level. Working
      capacity was assessed by ergospirometry on an exercise bicycle. Venous blood
      samples were taken before the test, when the expiratory exchange ratio (RER) was
      about 1.0 and immediately after completion of the test. SF-36 was used to
      evaluate the subject's functional status and well-being. RESULTS: The median
      working capacity in the patient group was 155 (85-190) W and 155 (125-215) W in
      the control group (n.s.) corresponding to 72 (43-97) % and 80 (59-97) %
      respectively of predicted values. Peak oxygen uptake was somewhat low in both
      groups when compared to P-O Astrands norms. Blood tests revealed that patients
      developed a slight metabolic hyperchloremic acidosis, not seen in the control
      group. There were no differences between the groups as assessed with SF-36.
      CONCLUSION: Patients with a continent urinary diversion have a working capacity
      equal to a control group despite a slight metabolic hyperchloremic acidosis.
      Quality of life was similar in the two groups and corresponded well with the
      norms for the general Swedish population aged 65 to 74.

PMID- 16442700
TI  - Validity and reliability of a questionnaire for evaluating nocturia, nocturnal
      enuresis and sleep-interruptions in an elderly population.
AB  - OBJECTIVES: To validate a new questionnaire evaluating nocturia, nocturnal
      enuresis and sleep-interruptions in an elderly population of men and women in
      Denmark. METHODS: The Nocturia, Nocturnal Enuresis and Sleep-interruption
      Questionnaire (NNES-Q) emerged from review of the literature and expert
      consensus. The questionnaire was a subset of a larger questionnaire comprising
      several domains on health status and voiding. Convergent and discriminatory
      validity was assessed in an unselected population of 2000 men and 2000 women 60
      80 years old. To test reproducibility, 400 respondents were mailed a separate
      questionnaire 2 weeks apart. A subgroup of men and women with and without
      nocturia was used for evaluating reliability of number of nocturia episodes.
      RESULTS: A total of 2825 (70.6%) filled in the questionnaire. A decrease in
      health status was correlated with increasing bother (range: -0.25 to -0.36,
      p<0.001, Spearman's r). These findings indicate acceptable convergent validity.
      Significant discriminatory validity was proven in separate groups of symptom
      severity (p<0.0001, Kruskal-Wallis test). Median kappa was 0.70 (range 0.58-0.86)
      indicating substantial agreement in the retest analysis. Number of nocturia
      episodes in questionnaires correlated with frequency volume charts (Spearman's
      rho 0.88; p<0.001). CONCLUSION: These data support that the NNES-Q has a good
      discriminatory and convergent validity, and is reliable over time. The NNES-Q may
      be useful in epidemiological studies and may also have a potential in daily
      clinical work up in patients with nocturia and nocturnal enuresis.

PMID- 16442701
TI  - Thyroid hormone action at the cellular, genomic and target gene levels.
AB  - Thyroid hormone (TH) plays important roles in metabolism, growth and
      differentiation. Thyroid hormone receptors (TRs) are ligand-regulatable
      transcription factors that bind both TH and DNA enhancer sequences in the
      promoter region of target genes where they can interact with co-repressor and co
      activator complexes. These interactons, in turn, have consequent effects on
      transcription. This review describes studies on TH action from our laboratory
      examining the cellular localization and motility of TRs using green fluorescent
      fusion proteins, gene expression profiles of TH in WT and TRalpha and TRbeta KO
      mice, as well as general transcription factor and co-activator recruitment on the
      promoters of target genes by TH in chromatin immunoprecipitation assays.

PMID- 16442702
TI  - Understanding the human estrogen receptor-alpha using targeted mutagenesis.
AB  - The estrogen receptor-alpha is a wonderfully complex protein important in normal
      biology, breast cancer, and as a target for anti-cancer agents. We are using the
      available structures of the hERalpha as well as secondary structure predictions
      to guide site-directed mutagenesis in order to test the importance of specific
      interactions and regions in the ligand-regulated activity of the protein. In one
      area of interest, we are investigating the role of the F domain in the ligand
      stimulated activity of the hERalpha. Results from our laboratory and others
      suggest that the F domain modulates the activity of the hERalpha. In order to
      better understand the role of the F domain in the hERalpha, we have constructed
      mutants within this region. Mutations within a predicted alpha-helical region
      alter the response of the ER to estradiol (E2), eliminate or impair the agonist
      activity of 4-hydroxytamoxifen (4-OHT), and alter the ability of E2 to overcome 4
      OHT's antagonist activity. Deleting the F domain increases the affinity of the
      receptor for E2; by contrast, mutating a residue in the middle of the predicted
      helix to a proline does not alter the affinity for E2, but does change the
      binding mechanism from a positive cooperative to a noncooperative interaction.
      These and other results show the F domain exhibits substantial functional
      complexity, and support the idea that this domain modulates the activity of the
      hERalpha. In a second area of interest, we are investigating the role of
      hydrophobic and hydrogen-bonding interactions at the start of helix 12 in the
      activity of the hERalpha. Leucine-536 (L536) has been proposed to participate in
      hydrophobic interactions that form part of a capping motif stabilizing the start
      of helix 12. When mutated, the resulting receptors exhibit a reduced response, or
      even an inverted response, to E2 and 4-OHT on both ERE-driven and AP-1-driven
      promoters. Interestingly, these mutated receptors also exhibit altered
      interactions with probes that recognize the agonist-bound and 4-OHT-bound
      conformations of the ERalpha. Thus, L536 couples the binding of ligand with the
      conformation of the receptor. Overall, these results show that combining
      structure-based hypotheses with functional tests of the ER's activity can
      identify regions and interactions that are important in the ligand-stimulated
      activity of the protein.

PMID- 16442703
TI  - Sperm phenotype of mice carrying a gene deletion for the plasma membrane
      calcium/calmodulin dependent ATPase 4.
AB  - The sarcolemmal calcium pumps (PMCA for plasma membrane calcium/calmodulin
      dependent ATPase) are a family of 10 transmembrane domain proteins ejecting
      calcium from the cytosol. They are encoded by four independent genes and at least
      21 splice variants have been described. Isoforms 1 and 4 are ubiquitous, whereas
      isoforms 2 and 3 are confined to neurons and few other cells (e.g. isoform 2 in
      the myocardium). In non-excitable cells they are thought to be the only calcium
      ejection systems and their function as governors of calcium balance is hence
      intuitive since cells cannot survive in a state of calcium overload. Differences
      in the affinity of the various isoforms for calcium, ATP and calmodulin have been
      described, but it is unclear whether the pumps have specialized functions over
      and above their 'housekeeping' role. In particular, in excitable cells, most
      calcium is ejected by the sodium/calcium exchanger suggesting that the PMCAs may
      have evolved into a specialized role. Recently, our group has identified a number
      of specialized functions of the PMCAs, notably a prominent regulatory role of
      PMCA4 (splice variant b) for neuronal NO synthase as well as for the Ras pathway.
      In addition, mice carrying a genetic deletion of the PMCA4 gene showed normal
      female, but completely infertile male animals. This is due to a highly specific
      defect in sperm motility, which is reduced to zero, with normal fertilization
      capacity. Overall, a scenario emerges where the plasma membrane calcium pumps
      fulfil roles far beyond the traditional housekeeping function, notably in cell
      signaling, sperm motility, and potentially in cell division. Consequently, we are
      currently exploring their potential as future drug targets for a variety of
      conditions, as well as their potential use in the development of a male
      contraception.

PMID- 16442704
TI  - Glycine-extended gastrin inhibits apoptosis in colon cancer cells via separate
      activation of Akt and JNK pathways.
AB  - Glycine-extended gastrin (G-Gly) is produced by colon cancers and has growth
      promoting and anti-apoptotic effects in the colonic epithelium. We have examined
      the anti-apoptotic effects of G-Gly and the signal transduction pathways
      involved. G-Gly stimulated HT-29 cell proliferation in a concentration dependent
      manner and inhibited serum-starvation and celecoxib-induced apoptosis. Inhibition
      of signalling via c-Jun NH2-terminal kinase (JNK) with SP600125 or PI3-kinase/Akt
      with LY294002 abolished the effects of G-Gly. G-Gly significantly increased
      phosphorylation of both JNK and Akt. The JAK2 inhibitor AG490 abolished the anti
      apoptotic effect of G-Gly and inhibited phosphorylation of Akt but not of JNK. G
      Gly stimulated tyrosine phosphorylation of JAK2. G-Gly-increased activation of AP
      1 was JNK-dependant and activation of STAT3 was JAK2-dependant. We conclude that
      G-Gly promotes growth and inhibits apoptosis in colon cancer cells. These effects
      are mediated via the JAK2, PI3-kinase/Akt and JNK pathways. Activation of JAK2 is
      upstream of Akt but not of JNK.

PMID- 16442705
TI  - Male genital tract antioxidant enzymes--their ability to preserve sperm DNA
      integrity.
AB  - Male germ cells are unique because they lose a bulk of their cytoplasm as
      cytoplasmic droplets when they develop, leading to a decrease in endogenous
      antioxidant and hence a dependence on extracellular antioxidant system to
      overcome oxidative stress. Spermatozoa are particularly vulnerable to oxidative
      stress because their plasma membrane is rich in polyunsaturated fatty acids and
      membrane-bound NADPH oxidase. To protect spermatozoa from oxidative attack, an
      optimal amount of reactive oxygen species is maintained by balancing the reactive
      oxygen species generated during sperm maturation in the epididymidis and
      antioxidants in secretions of the male reproductive tract. The male accessory sex
      glands secretions have been shown to be the major source of antioxidant enzymes
      in the ejaculate and have the important function of preserving sperm DNA
      integrity from oxidative stress experienced in the uterine environment. In our in
      vivo golden hamster model, ablation of the five major male accessory sex glands,
      namely the ampullary glands, coagulating glands, dorsolateral prostate, ventral
      prostate and seminal vesicle, was found to cause higher incidence and greater
      degree of DNA damage in spermatozoa. These damaged sperm are able to undergo
      fertilization at the same rate as intact ones; however, the outcome of embryos
      sired is seriously affected.

PMID- 16442706
TI  - Selective and opposing actions of progesterone receptor isoforms in human
      endometrial stromal cells.
AB  - Transcriptional regulation by progesterone is mediated primarily through the two
      progesterone receptor (PR) isoforms, PR-A and PR-B. Primary human endometrial
      stromal cell cultures, in which endogenous PR expression was lost, were infected
      with adenovirus expressing PR-A, PR-B, or both. Global gene expression analysis
      was conducted on vehicle and 30 nM progesterone (P4) treated cells following 12 h
      treatment. Interestingly, many genes regulated by PR-B alone or upon PR-A and PR
      B co-expression, did not overlap with each other or with the PR-A expression
      group. Although many genes known to be progestin regulated in the uterus in vivo
      were also regulated in this study, markedly little overlap with published P4
      regulated genes from human breast cancer cells was observed. Progesterone dose
      response curves were generated for several genes demonstrating gene selective
      potency and efficacy for each PR isoform. Furthermore, the PR isoforms opposed
      each other in regulation of tissue factor, with PR-B increasing and PR-A
      decreasing both mRNA and protein levels. Our data provide a view of global gene
      expression by PR isoforms in human endometrial cells and a comparison with other
      cell types. The specific genes and regulation patterns found provide groundwork
      to revealing the mechanism of PR isoform selectivity, and perhaps ultimately to
      the tissue selective properties these receptors appear to exhibit.

PMID- 16442707
TI  - Cell cycle inhibition by an anti-cyclin D1 antibodychemically modified for
      intracellular delivery.
AB  - Antibodies, especially monoclonal antibodies, are highly specific for their
      target antigens and have found extensive clinical application in the treatment of
      infectious diseases and neoplasia. However, they have a major shortcoming which,
      if overcome, would greatly expand their utility: an inability to penetrate the
      outer membrane of cells and act on intracellular targets. We demonstrated
      previously that this deficiency could be overcome by covalent linkage of an
      oligoarginine sequence to the conserved carbohydrate moiety present in the CH2
      region of immunoglobulins. Immune specificity was maintained but no attempt was
      made to test for biological activity related to specificity. Here, we report that
      a polyarginated monoclonal anti-cyclin D1 enters cells and inhibits cell cycle
      progression. We demonstrate this with NIH 3T3 cells and with two tumor cell
      lines, HT29 and SW480. As many tumors overexpress cyclin D1, an intracellular
      anti-cyclin D1, properly targeted, has the potential to be a novel broad range
      inhibitor of tumor cell multiplication. Moreover, success with intracellular anti
      cyclin D1 suggests that polyarginated antibodies, in general, could be a new,
      widely applicable experimental tool to investigate and influence intracellular
      processes, whether native to cells or introduced into cells by outside entities
      such as viruses.

PMID- 16442708
TI  - Photodynamic effects on nasopharyngeal carcinoma (NPC) cells with 5
      aminolevulinic acid or its hexyl ester.
AB  - Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Hong Kong and southern
      China. To explore a new modality of NPC treatment, 5-aminolevulinic acid (ALA) or
      its hexyl ester (ALA-H) mediated photodynamic therapy (PDT) was studied in vitro.
      The results show that NPC cells are sensitive to both ALA and ALA-H mediated PDT.
      However, ALA-H PDT is much more effective at cell inactivation than ALA-PDT, due
      to a higher efficiency of ALA-H on producing endogenous protoporphyrin (PpIX) in
      cells. Both apoptosis and necrosis are involved in cell death, but apoptosis
      plays a major role under the short time incubation of drugs. ALA and ALA-H
      mediated PDT not only destroy the cells directly, but also inhibit the expression
      of matrix metalloproteinase-2 (MMP2) in cells, a maker for tumor metastasis. The
      ALA-H shows promising PDT results on NPC in vitro; therefore it is worth
      investigating further in vivo for NPC treatment.

PMID- 16442710
TI  - Interleukin-6 level in patients with colorectal cancer.
AB  - Interleukin-6 (IL-6) contributes to a multitude of physiological and
      pathophysiological processes. We sought to determine the level of the IL-6 in
      serum and tumoral tissue of patients with staging of the tumor and whether serum
      IL-6 level in patients with colorectal cancer correlate with tumoral tissue level
      of it. Serum and tumoral tissue specimen (stored at -80 degrees C until the
      biochemical determination) from colorectal cancer (n=50) were examined for IL
      6.we determined the IL-6 Level in serum and tumoral tissue supernatant with
      Instant ELISA kit. A significant association between serum IL-6 level and staging
      of the tumor (P<0.001), tumoral tissue IL-6 level (r=0.95, P<0.001) in the
      patients was founded. IL-6 amount of the serum and tumoral tissue in the patients
      with colorectal cancer correlate significantly with the staging of the tumor and
      with each other.

PMID- 16442709
TI  - The Syk tyrosine kinase: a new negative regulator in tumor growth and
      progression.
AB  - The spleen tyrosine kinase Syk was long thought to be a hematopoietic cell
      specific signaling molecule. Recent evidence demonstrated that it is also
      expressed by many non-hematopoietic cell types and that it plays a negative role
      in cancer. A significant drop in its expression was first observed during breast
      cancer progression, but an anomalous Syk expression has now also been evidenced
      in many other tumor types. Mechanistic studies using Syk re-expression
      demonstrated its suppressive function in tumorigenesis and metastasis formation,
      which is surprising for a tyrosine kinase. Loss of Syk expression is regulated,
      albeit not exclusively, by its promoter hypermethylation. The molecular mechanism
      of its tumor-suppressive function remains largely unknown; the identification of
      its activators and effectors in non-hematopoietic cells will be a challenge for
      the years to come. An increasing number of clinical studies reveal a correlation
      between reduced Syk expression and an increased risk for metastasis formation,
      and assign Syk as a potential new prognostic marker in different tumor types.

PMID- 16442711
TI  - Removal of ammonium ion from aqueous solution using natural Turkish
      clinoptilolite.
AB  - A study on ion exchange kinetics and equilibrium isotherms of ammonium ion on
      natural Turkish clinoptilolite (zeolite) was conducted using a batch experiment
      technique. The effects of relevant parameters, such as temperature, contact time
      and initial ammonium (NH(4)(+)) concentration were examined, respectively. The
      pseudo first-order, pseudo second-order kinetic models and intraparticle
      diffusion model were used to describe the kinetic data. The pseudo second-order
      kinetic model provided excellent kinetic data fitting (R(2)>0.990) and
      intraparticle diffusion effects ammonium uptake. The Langmuir and Freundlich
      models were applied to describe the equilibrium isotherms for ammonium uptake and
      the Langmuir model agrees very well with experimental data. Thermodynamic
      parameters such as change in free energy (DeltaG(0)), enthalpy (DeltaH(0)) and
      entropy (DeltaS(0)) were also determined. An examination of the thermodynamic
      parameters shows that the exchange of ammonium ion by clinoptilolite is a process
      occurring spontaneously and physical in nature at ambient conditions (25 degrees
      C). The process is also found to be exothermic. The results indicate that there
      is a significant potential for the natural Turkish clinoptilolite as an adsorbent
      material for ammonium removal from aqueous solutions.

PMID- 16442712
TI  - Removal of p-xylene from an air stream in a hybrid biofilter.
AB  - Biofiltration of an air stream containing p-xylene has been studied in a
      laboratory hybrid biofilter packed with a mixture of mature pig compost, forest
      soil and the packing material which was made of polyethylene (PE) and used in the
      moving bed biological reactor (MBBR) in wastewater treatment. Three flow rates,
      9.17, 19.87 and 40.66 m(3)m(-2)h(-1), were investigated for p-xylene inlet
      concentration ranging from 0.1 to 3.3 g m(-3). A high elimination capacity of 80
      g m(-3)h(-1) corresponding to removal efficiency of 96% was obtained at a flow
      rate of 9.17 m(3)m(-2)h(-1) (empty bed residence time of 132 s). At a flow rate
      of 40.66 m(3)m(-2)h(-1) (empty bed residence time of 30s), the maximum
      elimination capacity for p-xylene was 40 g m(-3)h(-1) and removal efficiencies
      were in the range of 47-100%. The production of carbon dioxide (P(CO(2))) is
      proportional to elimination capacity (EC) and the linear relation was formulated
      as P(CO(2))=1.65EC+15.58. Stable pH values ranging from 6.3 to 7.6 and low
      pressure drop values less than 0.2 cm H(2)O (19.6 Pa) of packing media in compost
      based biofilter of hybrid biofilter were observed, which avoided acidification
      and compaction of packing media and sustained the activity of microorganism
      populations.

PMID- 16442713
TI  - Trihalomethanes formation potential of shrimp farm effluents.
AB  - Shrimp farm effluents along the Bangpakong River in the Chachoengsao Province of
      Thailand were evaluated for their trihalomethane formation potential (THMFP) and
      related parameters. The dissolved organic carbon (DOC), salinity and bromide ion
      concentrations of shrimp farm effluents were in the ranges of 12-14 mg/L, 0.1
      14.5 ppt, and 0-14 mg/L, respectively. The dissolved organic matter was
      fractionated into hydrophobic and hydrophilic fractions having a range
      concentration of 3-5 and 8-10mg/L, respectively. The THMFP for all shrimp farm
      effluents analyzed was in the range of 810-3100 microg/L. The hydrophilic organic
      fraction was found to be a more active precursor of trihalomethanes (THMs) with
      700-966 microg/L THMFP obtained from this fraction, while only 111-363 microg/L
      THMFP was derived from the hydrophobic fraction. The experimental results showed
      that salinity and bromide played crucial roles in the formation of THMs. At low
      salinity and bromide levels, chloroform was the dominant THM species, whereas at
      high salinity and bromide levels, bromoform became the dominant species. A
      Fourier Transform Infrared (FTIR) spectrum analysis of the samples before and
      after chlorination illustrated that the functional groups involved in the THM
      formation reaction were phenolic compounds, amines, aromatic hydrocarbons,
      aliphatic bromo-compounds, and aliphatic chloro-compounds.

PMID- 16442714
TI  - Air quality monitoring in Chennai, India, in the summer of 2005.
AB  - During the summer of 2005, concentrations of surface ozone (O(3)), oxides of
      nitrogen (NO(x)), respirrable suspended particulate matter (RSPM) and total
      suspended particulate matter (TSPM), relative humidity (RH), wind speed (WS) and
      wind direction (WD) were collected over successive periods of about 24 h at five
      sites. UV photometric ozone analyzer was used to measure the concentration of
      surface O(3). The study deals with the characteristics of hourly and daily mean
      surface O(3) under different climatic conditions, such as temperature, relative
      humidity, wind speed and wind direction and other pollutant concentrations. The
      maximum hourly O(3) concentration reached 53 ppb on 17th May. The ground-level
      O(3) concentration in Chennai varied between 2 and 53 ppb. The concentration of
      NO(x) and O(3) were below the prescribed limits. The TSPM values were exceeded
      the National Ambient Air Quality Standards (NAAQS) at Koyambedu, Mandaveli,
      Taramani and Vallalar Nagar study area.

PMID- 16442715
TI  - Impacts of dust on environmental systems and human health.

PMID- 16442716
TI  - Equilibrium data, isotherm parameters and process design for partial and complete
      isotherm of methylene blue onto activated carbon.
AB  - Equilibrium data for the adsorption of methylene blue onto activated carbon was
      reported. The equilibrium data were splitted to different data sets to have an
      idea on the partial and complete isotherm. The equilibrium data were analyzed
      using Freundlich, Langmuir and Redlich-Peterson isotherm. The influence of
      partial isotherm and complete isotherm on the equilibrium parameters in isotherm
      expression were estimated. Equilibrium data covering the complete isotherm is the
      best way to obtain the parameters in isotherm expressions. Present investigation
      showed that for successful batch sorber design, equilibrium data with partial
      isotherm is not sufficient, instead equilibrium data that covers complete
      isotherm is required. Redlich-Peterson and Langmuir isotherm well represent the
      adsorption of methylene blue onto activated carbon. Redlich-Peterson isotherm is
      a special case of Langmuir when the constant 'g' equals unity.

PMID- 16442717
TI  - Removal of chromium(III) from tannery wastewater using activated carbon from
      sugar industrial waste.
AB  - Chromium is commonly found in huge quantities in tannery wastewaters. For this
      reason, the removal and recovery of the chromium content of tannery wastewaters
      is crucial for environmental protection and economic reasons. Removal and
      recovery of chromium were carried out by using low-cost potential adsorbents. For
      this purpose three types of activated carbon; C1, the waste generated from sugar
      industry as waste products and the others (C2, C3) are commercial granular
      activated carbon, were used. The adsorption process and extent of adsorption are
      dependent on the physical and chemical characteristics of the adsorbent,
      adsorbate and experimental condition. The effect of pH, particle size and
      different adsorbent on the adsorption isotherm of Cr(III) was studied in batch
      system. The sorption data fitted well with Langmuir adsorption model. The
      efficiencies of activated carbon for the removal of Cr(III) were found to be
      98.86, 98.6 and 93 % for C1, C2 and C3, respectively. The order of selectivity is
      C1>C2>C3 for removal of Cr(III) from tannery wastewater. Carbon "C1" of the
      highest surface area (520.66 m(2)/g) and calcium content (333.3 mg/l) has the
      highest adsorptive capacity for removal of Cr(III). The results revealed that the
      trivalent chromium is significantly adsorbed on activated carbon collected from
      sugar industry as waste products and the method could be used economically as an
      efficient technique for removal of Cr(III) and purification of tannery
      wastewaters.

PMID- 16442718
TI  - Utilization of municipal solid waste incineration (MSWI) fly ash in blended
      cement Part 1: Processing and characterization of MSWI fly ash.
AB  - This paper is the first of a series of two articles dealing with the processes
      applied to MSWI fly ash with a view to reusing it safely in cement-based
      materials. Part 1 presents two stabilization processes and Part 2 deals with the
      use of the two treated fly ashes (TFA) in mortars. Two types of binder were used:
      an Ordinary Portland Cement (OPC) containing more than 95% clinker (CEM I 52.5R)
      and a binary blend cement composed of 70% ground granulated blast furnace slag
      and 30% clinker (CEM III-B 42.5N). In this first part, two stabilization
      processes are presented: the conventional process, called "A", based on the
      washing, phosphation and calcination of the ash, and a modified process, called
      "B", intended to eliminate metallic aluminum and sulfate contained in the ash.
      The physical, chemical and mineralogical characteristics of the two TFA were
      comparable. The main differences observed were those expected, i.e. TFA-B was
      free of metallic aluminum and sulfate. The mineralogical characterization of the
      two TFAs highlighted the presence of large amounts of a calcium aluminosilicate
      phase taking two forms, a crystalline form (gehlenite) and an amorphous form.
      Hydration studies on pastes containing mixed TFA and calcium hydroxide showed
      that this phase reacted with calcium hydroxide to form calcium aluminate
      hydrates. This formation of hydrates was accompanied by a hardening of the
      pastes. These results are very encouraging for the reuse of such TFA in cement
      based materials because they can be considered as pozzolanic additions and could
      advantageously replace a part of the cement in cement-based materials. Finally,
      leaching tests were carried out to evaluate the environmental impact of the two
      TFAs. The elements which were less efficiently stabilized by process A were zinc,
      cadmium and antimony but, when the results of the leaching tests were compared
      with the thresholds of the European landfill directive, TFA-A could nevertheless
      be accepted at landfills for non-hazardous waste. The modifications of the
      process led to a significant reduction in the stabilization of chromium, selenium
      and antimony.

PMID- 16442719
TI  - Biosorption characteristics of Bacillus sp. ATS-2 immobilized in silica gel for
      removal of Pb(II).
AB  - The bacterial strain Bacillus sp. ATS-2 isolated from Pb(II) polluted soil was
      immobilized with a silica matrix and Pb(II) biosorption properties of immobilized
      biosorbent were examined. Optimum biosorption conditions were investigated in the
      fixed bed column with the variation in the parameters of pH, bed length, flow
      rate and influent concentration. The Pb(II) biosorption equilibrium was attained
      within 60 min and the maximum biosorption yield for silica gel immobilized
      Bacillus sp. ATS-2 was determined as 91.73% at pH 4.0. The higher biosorption
      yields were observed at flow rates of 60 and 180 ml h(-1). The optimum bed length
      for the column was found as 10 cm. Data obtained from batch studies were
      evaluated by Freundlich, Langmuir and Dubinin-Radushkevich (D-R) isotherm models.
      The maximum monolayer capacity of Bacillus sp. ATS-2 for Pb(II) was 2.36 x 10(-5)
      mol g(-1). The involvement of the functional groups on the surface of immobilized
      cells in biosorption process was also evaluated by FTIR spectral analysis.

PMID- 16442720
TI  - Trivalent chromium removal from wastewater using low cost activated carbon
      derived from agricultural waste material and activated carbon fabric cloth.
AB  - An efficient adsorption process is developed for the decontamination of trivalent
      chromium from tannery effluents. A low cost activated carbon (ATFAC) was prepared
      from coconut shell fibers (an agricultural waste), characterized and utilized for
      Cr(III) removal from water/wastewater. A commercially available activated carbon
      fabric cloth (ACF) was also studied for comparative evaluation. All the
      equilibrium and kinetic studies were conducted at different temperatures,
      particle size, pHs, and adsorbent doses in batch mode. The Langmuir and
      Freundlich isotherm models were applied. The Langmuir model best fit the
      equilibrium isotherm data. The maximum adsorption capacities of ATFAC and ACF at
      25 degrees C are 12.2 and 39.56 mg/g, respectively. Cr(III) adsorption increased
      with an increase in temperature (10 degrees C: ATFAC--10.97 mg/g, ACF--36.05
      mg/g; 40 degrees C: ATFAC--16.10 mg/g, ACF--40.29 mg/g). The kinetic studies were
      conducted to delineate the effect of temperature, initial adsorbate
      concentration, particle size of the adsorbent, and solid to liquid ratio. The
      adsorption of Cr(III) follows the pseudo-second-order rate kinetics. From kinetic
      studies various rate and thermodynamic parameters such as effective diffusion
      coefficient, activation energy and entropy of activation were evaluated. The
      sorption capacity of activated carbon (ATFAC) and activated carbon fabric cloth
      is comparable to many other adsorbents/carbons/biosorbents utilized for the
      removal of trivalent chromium from water/wastewater.

PMID- 16442721
TI  - Silicone emulsion-enhanced recovery of chlorinated solvents: batch and column
      studies.
AB  - Batch and column experiments were conducted to investigate the feasibility of
      flushing with silicone oil emulsion for the removal of chlorinated solvents,
      including trichloroethylene (TCE), perchloroethylene (PCE) and 1,2
      dichlorobenzene (DCB). In the batch experiments, solubilization potentials of
      emulsion and effects of surfactants as additives were examined. The emulsion
      prepared with 2% (v/v) silicone oil could solubilize 90.7% of 10,000 ppm TCE,
      97.3% of 4000 ppm PCE and 99.7% of 7,800 ppm DCB. Results of one-dimensional
      column studies indicated that aqueous solubility and sorption of contaminants
      determined the flushing efficiency. The addition of surfactants below their
      critical micelle concentration (CMC) did not affect the removal of chlorinated
      solvents in batch and column experiments. The results of this study show that
      flushing with oil-based emulsion can be applied to treat the chlorinated
      solvents.

PMID- 16442723
TI  - Celtek clay as sorbent for separation-preconcentration of metal ions from
      environmental samples.
AB  - The sorption conditions including pH of the aqueous solution, sample volume,
      etc., on Celtek clay of copper(II), cadmium(II), lead(II), chromium(III),
      nickel(II) and cobalt(II) ions from environmental samples has been studied. The
      effects of electrolytes as matrix on the preconcentration were also investigated
      with the recoveries >95%. The 3 sigma detection limits for copper, cadmium, lead,
      chromium, nickel and cobalt ions were found to be 0.25, 0.32, 0.73, 0.45, 0.50
      and 0.41 microg/l, respectively. The relative standard deviation was <10% for the
      determination of analytes. The procedure was validated by analysis of a NRCC-SLRS
      4 Riverine Water, SRM 1573a Tomato leaves and IAEA 336 Lichen standard reference
      materials. The developed method was successively utilized for the determination
      of Cu(II), Cd(II), Pb(II), Cr(III), Ni(II) and Co(II) in various samples
      including natural waters, wheat and human hair by flame atomic absorption
      spectrometry (FAAS) with satisfactorily results (recoveries>95% and
      R.S.D.'s<10%).

PMID- 16442722
TI  - Adsorption isotherms, kinetics and column operations for the removal of hazardous
      dye, Tartrazine from aqueous solutions using waste materials--Bottom Ash and De
      Oiled Soya, as adsorbents.
AB  - Adsorbents, Bottom Ash (a power plant waste) and De-Oiled Soya (an agricultural
      waste) exhibit good efficacy to adsorb a highly toxic dye, Tartrazine. Through
      the batch technique equilibrium uptake of the dye is observed at different
      concentrations, pH of the solution, dosage of adsorbents and sieve size of
      adsorbents. Langmuir and Freundlich adsorption isotherms are successfully
      employed on both the adsorbents and on the basis of these models the
      thermodynamic parameters are evaluated. Kinetic investigations reveal that more
      than 50% adsorption of dye is achieved in about 1h in both the cases, whereas,
      equilibrium establishment takes about 3-4h. The linear plots obtained in rate
      constant and mass transfer studies further confirm the applicability of first
      order rate expression and mass transfer model, respectively. The kinetic data
      treated to identify rate controlling step of the ongoing adsorption processes
      indicate that for both the systems, particle diffusion process is predominant at
      higher concentrations, while film diffusion takes place at lower concentrations.
      The column studies reveal that about 96% saturation of both the columns is
      attained during their exhaustion, while about 88 and 84% of the dye material is
      recovered by eluting dilute NaOH solution through exhausted Bottom Ash and De
      Oiled Soya columns, respectively.

PMID- 16442724
TI  - Adsorption of arsenate on synthetic goethite from aqueous solutions.
AB  - Goethite was synthesized from the oxidation of ferrous carbonate precipitated
      from the double decomposition of ferrous sulfate doped with sodium lauryl sulfate
      (an anionic surfactant) and sodium carbonate in aqueous medium. The specific
      surface area and pore volume of goethite were 103 m(2) g(-1) and 0.50 cm(3) g(
      1). Batch experiments were conducted to study the efficacy of removal of
      arsenic(V) using this goethite as adsorbent for solutions with 5-25 mg l(-1) of
      arsenic(V). The nature of adsorption was studied by zeta-potential measurements.
      The adsorption process followed by Langmuir isotherm and diffusion coefficient of
      arsenate was determined to be 3.84 x 10(11)cm(2)s(-1). The optimum pH of
      adsorption was found to be 5.0. The kinetics of adsorption was evaluated with 10
      mg l(-1) and 20 mg l(-1) of As(V) solutions and activation energy of adsorption,
      as calculated from isoconversional method was in the range of 20 kJ mol(-1) to 43
      kJ mol(-1). This suggests that the adsorption process is by diffusion at the
      initial phase and later through chemical control. FT-IR characterization of
      arsenic treated goethite indicated the presence of both AsOFe and AsO groups and
      supported the concept of surface complex formation.

PMID- 16442725
TI  - Speciation of Cr(III) and Cr(VI) in environmental samples by solid phase
      extraction on Ambersorb 563 resin.
AB  - A simple and sensitive method for the speciation, separation and preconcentration
      of Cr(VI) and Cr(III) in natural water, soil and sediment samples was developed.
      Cr(VI) has been separated from Cr(III) and preconcentrated as Cr(III)
      diphenylcarbazone complex by using Ambersorb 563 resin and determined by
      spectrophotometric method at 540 nm. Effect of analytical parameters such as
      sulfuric acid concentration, ligand volume, type of elution solution, sample
      volume, amount of resin and foreign ions were investigated. The presented
      procedure was successfully applied for the chromium speciation in various
      environmental samples with successfully results.

PMID- 16442726
TI  - Immobilization of cesium and strontium radionuclides in zeolite-cement blends.
AB  - Zeolites are preferred ion exchange materials for the removal of radioisotopes
      from aqueous nuclear wastes because of their selectivity, radiation and
      temperature stability, and good compatibility with the cement matrix. Loaded
      materials, which are not regenerated, are preferably embedded in a solid matrix
      prior to ultimate storage in a repository. The aim of the present study is to
      investigate the possibility of solidifying exhausted synthetic zeolite A, loaded
      with (137)Cs and/or (90)Sr radionuclides, in Ordinary Portland Cement (OPC).
      Several factors affecting the characteristics of the final solidified waste
      product towards safe disposal such as mechanical strength and leaching behavior
      of the radionuclides have been studied. A simplified mathematical model based on
      diffusion mechanism for cylindrical geometry waste matrix has been simulated to
      predict the release rates of the investigated radionuclides from cement matrix.
      The predicted values are discussed in relation to experimentally observed leach
      rates to confirm the proposed mechanism in the model. The obtained results showed
      that the presence of zeolite A in the final cemented wastes improve the
      mechanical characteristics of the solidified cement matrix (mechanical strength
      and setting times) towards the safety requirements and reduce considerably the
      radionuclides leach rates.

PMID- 16442727
TI  - Soil desiccation rate integration into empirical dust emission models for polymer
      suppressant evaluation.
AB  - Dust constitutes an environmental and human health menace in many regions of the
      world. The rate of soil desiccation is a significant determinant of the
      availability of fine soil particles for entrainment in air as dust. Dust
      suppressants such as polymer solutions can reduce soil desiccation rate, thereby
      reducing dust emission factor. Herein, a dust emission estimation methodology
      that involves the integration of desiccation time curves to find the average
      desiccation rate is formulated. This is combined with soil characteristics,
      stressor (environmental and possibly vehicle) characteristics and liquid content
      in soil to estimate potential emission factors. Using this methodology, the dust
      suppression potential of aqueous polyethylene oxide (PEO) solution was
      investigated experimentally with Na-montmorillonite (Na-mmt) as the model dust
      generating material. PEO with a molecular weight of 8 x 10(6) and at aqueous
      concentrations ranging from 0.5 to 10 g/L, was mixed with 10 g of Na-mmt (surface
      area=31.82+/-0.22 m2/g) and desiccated for 700 h in a specially designed chamber
      at 25 degrees C and 30% relative humidity. The results show that generally,
      aqueous PEO is superior to distilled water as a dust suppressant for Na-mmt at
      concentrations in the range of 0.5-2.0 g/L. The experimental data obtained are
      introduced into the formulated estimation methodology, and potential emissions of
      dust from PEO-admixed Na-mmt are determined.

PMID- 16442728
TI  - Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin suppresses contextual
      fear conditioning-accompanied activation of cyclic AMP response element-binding
      protein in the hippocampal CA1 region of male rats.
AB  - We investigated the effect of in utero and lactational exposures to dioxin on
      adult offspring with contextual fear conditioning, a sex- and hippocampus
      dependent learning paradigm; and we measured the conditioning-accompanied
      activation of cyclic AMP response element-binding protein (CREB) in the
      hippocampal CA1 region. Pregnant rats were treated with a low dose of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15. TCDD treatment decreased
      freezing time in conditioning tests of adult male offspring but not of female
      offspring. A similar, male-specific decrease was observed in the percentage of
      phosphorylated CREB-immunoreactive neurons in the CA1 region following
      conditioning in TCDD-treated rats. These results suggest that perinatal TCDD
      exposure impairs hippocampus-dependent learning in male offspring by suppressing
      CREB activation.

PMID- 16442729
TI  - Olfactory stimulation with scent of lavender oil affects autonomic
      neurotransmission and blood pressure in rats.
AB  - Previously, we observed that olfactory stimulation with scent of lavender oil
      (SLVO) suppressed sympathetic nerve activities and elevated gastric vagal
      (parasympathetic) nerve activity (GVNA), decreased plasma glycerol concentration
      and body temperature, and enhanced appetite in rats. Here, we further showed that
      olfactory stimulation with SLVO lowered renal sympathetic nerve activity (RSNA)
      and blood pressure (BP) and elevated GVNA in urethane-anesthetized rats.
      Olfactory stimulation with linalool, a component of lavender oil, also elicited
      decreases in RSNA and BP and an increase in GVNA in urethane-anesthetized rats.
      Anosmia induced by pretreatment of the nasal cavity by application of ZnSO4
      eliminated the effects of both SLVO and scent of linalool on RSNA, GVNA and BP.
      Furthermore, intracerebroventricular administration of thioperamide, a
      histaminergic H3-antagonist, abolished the suppression of RSNA and BP as well as
      the elevation of GVNA mediated by both SLVO and scent of linalool. Finally,
      bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) eliminated
      RSNA and BP suppression and the elevation of GVNA due to SLVO or linalool. Thus,
      it was concluded that scent of lavender oil and its active component, linalool,
      affects autonomic neurotransmission and reduces blood pressure through the
      central histaminergic nervous system and the SCN.

PMID- 16442731
TI  - Sex difference in Fos induced by male urine in medial amygdala-projecting
      accessory olfactory bulb mitral cells of mice.
AB  - We previously reported that exposure to soiled male bedding induced Fos protein
      immunoreactivity (Fos-IR) in significantly more neurons of the vomeronasal organ
      (VNO) and medial amygdala of gonadectomized, estradiol-treated female than male
      mice whereas no such sex difference was seen in the intervening mitral cells of
      the accessory olfactory bulb (AOB). We asked whether a sexually dimorphic
      functional response to male urinary pheromones might be revealed in AOB mitral
      cells that project specifically to the medial amygdala. Gonadectomized mice of
      both sexes were treated with estradiol and 3 days later received bilateral
      injections of the retrograde tracer, Cholera toxin-B (CTB) into the medial
      amygdala. Five days later male urine or saline was applied nasally to each
      subject 90 min prior to sacrifice, and sections of the AOB were processed for
      double-label fluorescent immunocytochemistry for Fos protein and CTB. In both the
      rostral and caudal AOB, there were significantly more double-labeled mitral cells
      in female than in male subjects following exposure to male urine. A sex
      difference in the responsiveness of VNO sensory neurons seen previously to male
      soiled bedding is reflected in a parallel sex difference in the responsiveness of
      AOB mitral cells when only AOB cells that project to the amygdala are examined
      and when male urine as opposed to soiled male bedding is used as the activating
      stimulus.

PMID- 16442730
TI  - Genetic influences on dynamic complexity of brain oscillations.
AB  - Human electroencephalogram (EEG) consists of complex aperiodic oscillations that
      are assumed to indicate underlying neural dynamics such as the number and degree
      of independence of oscillating neuronal networks. EEG complexity can be estimated
      using measures derived from nonlinear dynamic systems theory. Variations in such
      measures have been shown to be associated with normal individual differences in
      cognition and some neuropsychiatric disorders. Despite the increasing use of EEG
      complexity measures for the study of normal and abnormal brain functioning,
      little is known about genetic and environmental influences on these measures.
      Using the pointwise dimension (PD2) algorithm, this study assessed heritability
      of EEG complexity at rest in a sample of 214 young female twins consisting of 51
      monozygotic (MZ) and 56 dizygotic (DZ) pairs. In MZ twins, intrapair correlations
      were high and statistically significant; in DZ twins, correlations were
      substantially smaller. Genetic analyses using linear structural equation modeling
      revealed high and significant heritability of EEG complexity: 62-68% in the eyes
      closed condition, and 46-60% in the eyes-open condition. Results suggest that
      individual differences in the complexity of resting electrocortical dynamics are
      largely determined by genetic factors. Neurophysiological mechanisms mediating
      genetic variation in EEG complexity may include the degree of structural
      connectivity and functional differentiation among cortical neuronal assemblies.

PMID- 16442733
TI  - Obtaining TEM images with a uniform deviation parameter.
AB  - In transmission electron microscopes made during the last quarter of a century,
      it has been impossible to take images in which the diffraction contrast
      conditions are uniform across the field of view. This is inconvenient when, for
      example, imaging dislocations at a relatively low magnification. The problem
      arises because modern microscopes use immersion lenses in which the sample sits
      in a high magnetic field. The resulting helical trajectories of the electrons at
      the sample plane mean that it is not possible to make a beam that is parallel at
      the sample. Results of a method to overcome this problem are presented. It is
      shown that a simple modification to the microscope (which, on a computer
      controlled microscope, could be implemented in software) can be used to produce
      images in which the deviation parameter is essentially constant across many
      microns of image. By a happy accident, this method can be used, not only to
      correct for the helicity imparted by immersion lenses, but also to correct for
      buckling of the sample (up to a point).

PMID- 16442734
TI  - Polarization dependence in ELNES: influence of probe convergence, collector
      aperture and electron beam incidence angle.
AB  - The differential scattering cross section in electron energy loss near edge
      spectroscopy (ELNES) generally depends on the orientation of the Q wave vector
      transferred from the incident electron to an atomic core electron. In the case
      where the excited atom belongs to a threefold, fourfold or sixfold main rotation
      axis, the dipole cross section depends on the angle of Q with respect to this
      axis. In this paper, we restrict to this situation called dichroism. Furthermore,
      if we take into account the relativistic effects due to the high incident
      electron velocity, this dipole cross section also depends on the angle of Q with
      respect to the electron beam axis. It is due to these dependences that the shape
      of measured electron energy loss spectra varies with the electron beam incidence,
      the collector aperture, the incident beam convergence and the incident electron
      energy. The existence of a particular beam incidence angle for which the
      scattering cross section becomes independent of collection and beam convergence
      semi-angles is clearly underscored. Conversely, it is shown that EELS spectra do
      not depend on the beam incidence angle for a set of particular values of
      collection and convergence semi-angles. Particularly, in the case of a parallel
      incident beam, there is a collection semi-angle (often called magic angle) for
      which the cross section becomes independent of the beam orientation. This magic
      angle depends on the incident beam kinetic energy. If the incident electron
      velocity V is small compared with the light velocity c, this magic angle is about
      3.975theta(E) (theta(E) is the scattering angle). It decreases to 0 when V
      approaches c. These results are illustrated in the case of the K boron edge in
      the boron nitride.

PMID- 16442732
TI  - Mapping of odor-related neuronal activity using a fluorescent derivative of
      glucose.
AB  - Activity labeling was applied to the olfactory systems of the terrestrial slug
      Limax valentianus using 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2
      deoxyglucose (2-NBDG), a fluorescent derivative of glucose. 2-NBDG was
      incorporated into cultured Limax olfactory interneurons, and this was partially
      blocked by the presence of a high concentration of glucose in the medium,
      indicating that a part of the uptake of 2-NBDG is mediated by glucose
      transporters. Next, in order to map odor-related neuronal activity in the primary
      olfactory center, tentacular ganglion, we injected 2-NBDG into the body cavities
      of slugs and exposed them to odors or clean air (control). In the odor-stimulated
      animals, the cell mass region was strongly stained. The digit-like extensions and
      the neuropil region were also stained in some animals. The control animals showed
      no staining. The neurons in the cell mass are thought to be involved in
      generating oscillating activities in the tentacular ganglion, and their
      activation may imply modulation of oscillatory activity during odor processing.
      Our results show that 2-NBDG is useful for mapping neuronal activity in vivo.

PMID- 16442735
TI  - Expression of C-terminal truncated and full-length Babesia bigemina rhoptry
      associated protein 1 and their potential use in enzyme-linked immunosorbent
      assay.
AB  - Recombinant antigen-based enzyme-linked immunosorbent assay (ELISA) was developed
      for the serological diagnosis of Babesia bigemina infection by using a full
      length B. bigemina rhoptry-associated protein 1 (rRAP-1) and the truncated C
      terminal RAP-1 (rRAP-1/CT). While the rRAP-1 showed cross reactivity between B.
      bigemina- and Babesia bovis-infected bovine sera, the rRAP-1/CT was highly
      specific to B. bigemina-infected bovine sera and proved useful in the detection
      of sequential sera collected from an experimentally infected cow during the acute
      and latent infection. The high yield of soluble rRAP-1/CT and its diagnostic
      specificity demonstrate its potential in the diagnosis of B. bigemina infection.
      Its usefulness for epidemiological investigation is currently being evaluated.

PMID- 16442736
TI  - The nitrate/nitrite ABC transporter of Phormidium laminosum: phosphorylation
      state of NrtA is not involved in its substrate binding activity.
AB  - Most cyanobacteria take up nitrate or nitrite through a multisubunit ABC
      transporter (ATP-binding cassette) located in the cytoplasmic membrane. Nitrate
      and nitrite transport activity is instantaneously blocked by the presence of
      ammonium in the medium. Previous biochemical studies reported the existence of
      phosphorylation/dephosphorylation events of the nitrate transporter (NRT) related
      to the presence of ammonium-sensitive kinase/phosphatase activities in plasma
      membranes of the cyanobacterium Synechococcus elongatus PCC 6301. In this work,
      we have analyzed the biochemical properties of the periplasmic nitrate/nitrite
      binding subunit (NrtA) of NRT from the thermophilic nondiazotrophic
      cyanobacterium Phormidium laminosum. Our results show that cyanobacterial NrtA is
      phosphorylated in vivo. However, substrate binding activity in vitro is not
      affected by the phosphorylation state of the protein, ruling out the possibility
      that phosphorylation/dephosphorylation of NrtA is involved in the regulation of
      the nitrate/nitrite uptake by NRT transporter. Moreover, NrtA is present as
      multiple isoforms showing the same molecular mass but different isoelectric
      points ranging from pI 5 to 6. Mass spectrometric characterization of NrtA
      isoforms shows that the protein is phosphorylated at residue Tyr203, and contains
      several methionine sulphoxide residues which account for the observed isoforms.
      Both phosphorylated and non-phosphorylated forms of NrtA are active in vitro,
      showing comparable binding affinity for nitrate and nitrite. Both substrates
      behave as pure competitive inhibitors with a binding stoichiometry of one
      molecule of anion per NrtA monomer.

PMID- 16442737
TI  - Early signs of motoneuron vulnerability in a disease model system:
      Characterization of transverse slice cultures of spinal cord isolated from
      embryonic ALS mice.
AB  - Mutations in the SOD1 gene are associated with familial amyotrophic lateral
      sclerosis. The mechanisms by which these mutations lead to cell loss within the
      spinal cord ventral horns are unknown. In the present report we used the G93A
      transgenic mouse model of amyotrophic lateral sclerosis to develop and
      characterize an in vitro tool for the investigation of subtle alterations of
      spinal tissue prior to frank neuronal degeneration. To this aim, we developed
      organotypic slice cultures from wild type and G93A embryonic spinal cords. We
      combined immunocytochemistry and electron microscopy techniques to compare wild
      type and G93A spinal cord tissues after 14 days of growth under standard in vitro
      conditions. By SMI32 and choline acetyl transferase immunostaining, the
      distribution and morphology of motoneurons were compared in the two culture
      groups. Wild type and mutant cultures displayed no differences in the analyzed
      parameters as well as in the number of motoneurons. Similar results were observed
      when glial fibrillary acidic protein and myelin basic protein-positive cells were
      examined. Cell types within the G93A slice underwent maturation and slices could
      be maintained in culture for at least 3 weeks when prepared from embryos.
      Electron microscopy investigation confirmed the absence of early signs of
      mitochondria vacuolization or protein aggregate formation in G93A ventral horns.
      However, a significantly different ratio between inhibitory and excitatory
      synapses was present in G93A cultures, when compared with wild type ones,
      suggesting the expression of subtle synaptic dysfunction in G93A cultured tissue.
      When compared with controls, G93A motoneurons exhibited increased vulnerability
      to AMPA glutamate receptor-mediated excitotoxic stress prior to clear disease
      appearance. This in vitro disease model may thus represent a valuable tool to
      test early mechanisms contributing to motoneuron degeneration and potential
      therapeutic molecular interventions.

PMID- 16442738
TI  - Modulation of somatosensory event-related potential components in a tactile
      visual cross-modal task.
AB  - Human tactile discrimination studies have shown that visual stimuli enhance
      tactile performance. Other studies on event-related potentials showed that
      somatosensory N140 was enhanced when attention of human subjects was directed to
      tactile stimuli. Therefore, we hypothesized that N140 would be modulated when
      human subjects performed tactile cross-modal delay tasks. Scalp-event-related
      potentials were recorded from normal subjects performing either a tactile-tactile
      unimodal, or a tactile-visual cross-modal delayed matching-to-sample task.
      Identical tactile stimuli were used in both tasks. N140 component evoked by the
      tactile stimuli was enhanced in the cross-modal task. Enhancement of this
      component was also observed in control cross-modal tasks. The results suggest
      that tactile-visual cross-modal association affects tactile sensory-perceptual
      processes in humans.

PMID- 16442739
TI  - Hypoxia-induced desensitization and internalization of adenosine A1 receptors in
      the rat hippocampus.
AB  - Activation of A1 adenosine receptors is important for both the neuromodulatory
      and neuroprotective effects of adenosine. However, short periods of global
      ischemia decrease A1 adenosine receptor density in the brain and it is not known
      if a parallel loss of functional efficiency of A1 adenosine receptors occurs. We
      now tested if hypoxia leads to changes in the density and efficiency of A1
      adenosine receptors to inhibit excitatory synaptic transmission in rat
      hippocampal slices. In control conditions, the adenosine analog 2
      chloroadenosine, inhibited field excitatory post-synaptic potentials with an EC50
      of 0.23 microM. After hypoxia (95% N2 and 5% CO2, for 60 min) and reoxygenation
      (30 min), the EC50 increased to 0.73 microM. This EC50 shift was prevented by the
      presence of the A1 adenosine receptor antagonist 8-phenyltheophyline, but not by
      the A(2A)R antagonist 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]
      1,2,4-triazolo[1,5-c] pyrimidine, during the hypoxic period. This decreased
      efficiency of A1 adenosine receptors was not paralleled by a global change of A1
      adenosine receptor density or affinity (as evaluated by the binding parameters
      obtained in nerve terminal membranes). However, the density of biotinylated A1
      adenosine receptors at the plasma membrane of nerve terminals was reduced by 30%
      upon hypoxia/reoxygenation, in a manner prevented by the A1 adenosine receptor
      antagonist 1,3-dipropyl-8-cyclopentylxanthine and mimicked by prolonged (60 min)
      supra-maximal activation of A1 adenosine receptors with 2-chloroadenosine (10
      microM). These results indicate that hypoxia leads to a rapid (<90 min)
      homologous desensitization of A1 adenosine receptor-mediated inhibition of
      synaptic transmission that is likely due to an internalization of A1 adenosine
      receptors in nerve terminals.

PMID- 16442740
TI  - 7beta-hydroxycholesterol reduces the extent of reactive gliosis caused by iron
      deposition in the hippocampus but does not attenuate the iron-induced seizures in
      rats.
AB  - 7beta-Hydroxycholesterol has been previously demonstrated to inhibit astrocytosis
      in injured cortex or spinal cord of rats. In this study, we explored the
      inhibitory effects of the liposome containing 7beta-hydroxycholesterol on the
      reactive astrocytosis caused by the injection of iron into the hippocampus of
      rats and furthermore evaluated the involvement of reactive astrocytosis in iron
      induced epilepsy. Injection of ferric chloride solution unilaterally into the
      hippocampus of rats induced spontaneous spiking activity ipsilaterally then
      developed into bilateral hippocampi and generalized convulsive seizures within
      the first week post-operation, and spontaneous epileptiform activity and
      generalized seizures lasted as long as 2 weeks post-operation, whereas none of
      the rats injected with sodium chloride solution unilaterally into the hippocampus
      developed generalized seizures. With immunohistochemistry and Western blot
      analyses, apparent reactive astrocytosis in bilateral hippocampi was detected
      using antibody against glial fibrillary acidic protein 14 days after the
      injection of ferric chloride solution, but no significant differences were found
      in the amount of synaptophysin protein, a presynaptic vesicle protein, as
      compared with the rats injected with sodium chloride solution. Infusion of
      liposome suspension containing 7beta-hydroxycholesterol into the same site
      immediately after the injection of ferric chloride solution reduced the extent of
      the reactive astrocytosis by 50%-55% of the amount of glial fibrillary acidic
      protein in the hippocampi of both hemispheres, and non-significantly elevated the
      amount of synaptophysin protein in both sides of hippocampus. However, these
      effects did not significantly modify the seizure latency and the incidence of
      generalized seizures in the rats. These findings demonstrate the effects of 7beta
      hydroxycholesterol on the inhibition of reactive astrocytosis caused by iron
      deposition in the hippocampus of rats, and suggest that the reactive astrocytosis
      may not play a causal role in the development of iron-induced seizures.

PMID- 16442741
TI  - Increased sensitivity to restraint stress and novelty-induced emotionality
      following long-term, high dose cannabinoid exposure.
AB  - Cannabinoids have long been known to affect anxiety, emotionality and stress
      responsivity; however, the direction of this effect has been controversial. This
      research aimed to compare the effects of chronic administration of both a very
      low dose (5 microg/kg) and a very high dose (100 microg/kg) of the potent
      cannabinoid CB(1) receptor agonist HU-210 on emotionality and stress
      responsivity. Twelve day administration of the high dose of HU-210 increased
      anxiety-like behavior as indicated by a significant reduction in time spent in
      the central quadrant and an increase in fecal boli in the open field test.
      However, neither dose of HU-210 elicited any significant behavioral effect in the
      elevated plus maze. Stress responsivity appeared to be sensitized in animals that
      had received high dose HU-210 treatment, as 30 min of restraint resulted in
      significantly higher plasma corticosterone levels in these subjects than in
      stressed controls or those receiving the low dose treatment. Furthermore,
      restraint stress elicited a non-significant increase in c-fos induction in the
      central amygdala, which was significantly potentiated following high-dose
      treatment with HU-210. This interaction was not seen in the basolateral amygdala.
      Together, these findings suggest that chronic high dose, but not low dose,
      cannabinoid administration may result in increased emotionality and sensitization
      of the stress axis.

PMID- 16442743
TI  - The thermoregulatory-vascular remodeling hypothesis: an explanation for essential
      hypertension.
AB  - The supposition that temperature homeostasis has precedence over blood pressure
      homeostasis, that vascular remodeling ensues, that hypertension is the
      consequence and that sodium chloride ingestion sets the sequence in motion,
      constitutes the thermoregulatory-vascular remodeling hypothesis. Because the
      cardiovascular system plays a role in both temperature and blood pressure
      regulation, the ingestion of sodium chloride creates conflict between temperature
      homeostasis and blood pressure homeostasis. Vasodilatation would lower the blood
      pressure following the ingestion of sodium chloride, but increased blood flow to
      the cutaneous circulation would increase heat loss and decrease core body
      temperature. Regional vasodilatation that does not involve the cutaneous
      circulation could lower the blood pressure without lowering the core temperature,
      but if temperature homeostasis has precedence over blood pressure homeostasis,
      and if regional vasodilatation incompletely restores blood pressure homeostasis,
      then elevations in blood pressure may persist following the ingestion of sodium
      chloride. The kidneys gradually excrete the excess sodium chloride, thereby
      normalizing the blood pressure, but prolonged elevations in blood pressure lead
      to vascular remodeling, sustained increases in peripheral resistance, and a
      higher baseline blood pressure. Following countless sodium chloride ingestions,
      essential hypertension develops. The thermoregulatory-vascular remodeling
      hypothesis predicts that antihypertensive medications that are vasodilators will
      accelerate heat loss due to increased blood flow to the cutaneous circulation. As
      a result, either core body temperature will decrease or there will be a
      compensatory increase in the metabolic rate. This prediction could be tested
      experimentally. The main clinical implication of the thermoregulatory-vascular
      remodeling hypothesis is that avoiding the ingestion of sodium chloride is the
      key to preventing essential hypertension.

PMID- 16442742
TI  - Excessive drinking and other problem behaviours among 14-16 year old
      schoolchildren.
AB  - The study investigates excessive drinking and associations with other problem
      behaviours in 2078 school students aged 14-16 years in seven London secondary
      schools. Using a cross-sectional design, a self-completion questionnaire assessed
      lifetime and recent (past month) alcohol and drug consumption, attitudes to
      alcohol use education, alcohol-related problems, psychological problems,
      educational aspirations, truancy, and delinquent behaviour. Excessive drinking
      was operationally defined as 10 or more units of alcohol per drinking occasion.
      At least one episode of excessive drinking was reported by 32% of the sample,
      with 10% reporting five or more episodes. Excessive drinking was positively
      associated with frequency of cigarette smoking, use of cannabis, positive
      attitudes towards illicit drugs, low educational aspirations, higher depression
      scores, frequent truancy, and involvement in delinquent behaviours. Excessive
      drinking is a problematic behaviour in its own right but it is also a marker for
      other problem behaviours, including illicit drug misuse and delinquency.
      Understanding and responding to alcohol misuse among adolescents requires
      attention to psychological, social and developmental factors other than alcohol
      consumption alone.

PMID- 16442744
TI  - epsilon-Glycation, APP and Abeta in ageing and Alzheimer disease: a hypothesis.
AB  - The post-translational modifications of protein molecules include glycation,
      which may not only occur enzymatically controlled in N and O position, but also
      wherever proteins meet reducing sugars non-enzymatically in epsilon position at
      lysines (non-enzymatic (epsilon) glycation (NEG)). The formation of keto-amines
      from the amine-sugar compounds (Amadori re-arrangement) and further processing of
      the largely undigestible Amadori compounds eventually results in insoluble
      advanced glycation end products (AGEs). The latter can induce or favour disease
      including mental disorders. Preferential targets of NEG include large cell
      surface proteins. Ample evidence has been provided that NEG also occurs in the
      brain where cross-linking of epsilon-glycated proteins, induction of oxidative
      stress and signalling of AGEs through their specific receptor (RAGE) likely play
      a role in (brain) ageing and Alzheimer disease (AD). This is underscored by the
      demonstration of particular interactions between AGE/RAGE and amyloid-beta
      (Abeta) that favour the aggregation and deposition of Abeta and, perhaps, the
      formation of Abeta itself. The close relationship between NEG and Abeta, as well
      as other facts foster the hypothesis that NEG of the large trans-membrane amyloid
      precursor protein (APP) might be a significant factor in the induction of
      aberrant APP cleavage with production of Abeta, not only in normal ageing, but
      also in AD. Blockade of lysine cleavage sites on APP by sugar chains or marker
      effects induced by NEG akin to ubiquitination of proteins for degradation at
      lysines could be expected to contribute to altered processing of APP. The
      hypothesis of epsilon-glycation in APP proposed here and the review of evidences
      for the significance of NEG in brain ageing and AD are aimed at the stimulation
      of investigations into the still open question which role NEG plays with respect
      to APP and its abnormal processing in AD. It can be rendered likely that such
      research might open new avenues towards decreasing the risk of AD and/or slowing
      its progression through the prevention of NEG in APP with aberrant APP
      processing, increased generation of Abeta and the formation of AGEs from epsilon
      glycated APP.

PMID- 16442745
TI  - The impact of imperfect vaccines on the evolution of HIV virulence.
AB  - A theoretical framework is proposed on which some hypotheses related to the
      impact of imperfect vaccines on the evolution of HIV virulence can be tested. For
      this, a linear increase of risk behaviour with vaccine efficacy is assumed. This
      is based on the hypothesis that people are prone to relax preventive measures by
      knowing that they and their partners are vaccinated and that this effect is more
      intense the more effective the vaccine is known to be. An additional, and perhaps
      more important hypothesis is related to the theoretical possibility that
      increased risk behaviour of some vaccinated individuals in partially protected
      populations could act as a selective pressure toward more virulent HIV strains.
      Those hypotheses were tested by a mathematical model that considers three
      different HIV strains competing against each other in a population partially
      protected by imperfect vaccines of distinct efficacies. Simulations of the model
      demonstrated that, under the above hypotheses, there is a shift in HIV virulence
      towards more aggressive strains with increase in vaccine efficacy, associated
      with a marked reduction in the total amount of transmission and, consequently, in
      the prevalence of HIV. Potential ways for further testing the theory/model and
      the implications of the results are discussed.

PMID- 16442746
TI  - Could hair dyes cause hair loss?

PMID- 16442747
TI  - A brief study of a possible relation of epilepsy association with meditation.

PMID- 16442748
TI  - Odour learning and immunity costs in mice.
AB  - There is accumulating evidence that learning is metabolically costly. One way in
      which this may manifest itself is in trade-offs between learning effort and
      immune function, with learning increasing susceptibility to infection. We tested
      this idea in the context of odour learning using outbred (BKW) male laboratory
      mice. Mice were exposed to three experimental treatments in which they were
      required to learn different numbers of urinary odours. While treatment affected
      the extent to which mice habituated to test odours during training, differences
      were not a simple function of the number of odours. The fact that there was also
      no significant effect of treatment on the degree of preference for novel over
      familiar odours in subsequent tests suggests mice retained learned odour profiles
      equally well regardless of the number of odours. That subsequent infection with
      Babesia microti increased with the number of odours mice had to learn is then
      consistent with an increased cost to learning effort when more odours were
      presented. Analysis within treatments, and relationships with the change in
      corticosterone concentration over the period of the experiment, suggested that it
      was a failure to learn, rather than maintaining learning performance, in more
      difficult learning tasks that led to greater infection. As in a previous study of
      maze learning in the strain, there was no direct relationship between infection
      and measures of peripheral antibody (total IgG) titre. The results are discussed
      in relation to studies in other learning contexts and reported relationships
      between glucocorticoid hormones and learning outcomes.

PMID- 16442749
TI  - Temporal stability of novelty exploration in mice exposed to different open field
      tests.
AB  - We investigated behavioural activity and temporal distribution (patterning) of
      mouse exploration in different open field (OF) arenas. Mice of 129S1 (S1) strain
      were subjected in parallel to three different OF arenas (Experiment 1), two
      different OF arenas in two trials (Experiment 2) or two trials of the same OF
      test (Experiment 3). Overall, mice demonstrated a high degree of similarity in
      the temporal profile of novelty-induced horizontal and vertical exploration
      (regardless of the size, colour and shape of the OF), which remained stable in
      subsequent OF exposures. In Experiments 4 and 5, we tested F1 hybrid mice (BALB/c
      S1; NMRI-S1), and Vitamin D receptor knockout mice (generated on S1 genetic
      background), again showing strikingly similar temporal patterns of their OF
      exploration, despite marked behavioural strain differences in anxiety and
      activity. These results suggest that mice are characterised by stability of
      temporal organization of their exploration in different OF novelty situations.

PMID- 16442750
TI  - A systematic literature review of tobacco use among adults 15 years and older in
      sub-Saharan Africa.
AB  - BACKGROUND: Given that developing countries (and particularly women in these
      countries) are at increasing risk for tobacco use, the need for hard data to
      accurately monitor tobacco use in developing countries is needed. The purpose of
      this review is to synthesize the available prevalence data on current tobacco use
      among adults in sub-Saharan Africa (SSA). METHODS: Several databases were
      systematically searched for articles published in peer-reviewed journals at any
      time during the last century to mid-2005. The search resulted in the retrieval of
      54 articles in which the current use of tobacco, cigarettes, cigars and snuff
      were reported. They were conducted in 14 of the 48 SSA countries. RESULTS: Cross
      country comparisons revealed that the prevalence, and intensity (frequency and/or
      quantity) of tobacco use was higher among males compared to females across all
      countries. Certain racially classified social groups in South Africa were at
      increased risk for tobacco use. Males aged between 30 and 49 years used tobacco
      at higher rates than those younger or older than this age range. Among females,
      prevalence rates of smoked tobacco use increased steadily with age. There was no
      clear pattern regarding socio-economic status (SES) or urban/rural differences.
      The onset of tobacco use mostly occurs in late adolescence or early adulthood.
      CONCLUSIONS: While in many SSA countries the prevalence of tobacco use among
      adults is relatively low compared to developed and other developing countries,
      prevention, interventions and policies should work towards reducing these levels
      by targeting the at risk populations identified from this review.

PMID- 16442751
TI  - An improved protocol for electrotransformation of Corynebacterium
      pseudotuberculosis.
AB  - We developed an improved protocol for the electrotransformation of
      Corynebacterium pseudotuberculosis, testing variations of parameters in the
      procedures that are routinely used for the preparation of electrocompetent cells
      of this species, including (i) culture conditions, (ii) cell growth phase, (iii)
      electroporation solutions and (iv) quantity of plasmid DNA. We obtained the
      greatest efficiency of transformation when the cells were grown until the
      stationary phase and then washed with 10% glycerol electroporation solution. The
      transformation efficiency was inversely proportional to the quantity of plasmid
      DNA. The transformation efficiency reached 10(5) colony-forming units (cfu)/mug
      plasmid DNA. This protocol would be useful for genetic studies of C.
      pseudotuberculosis.

PMID- 16442752
TI  - Agreement between three ELISAs for Mycobacterium avium subsp. paratuberculosis in
      dairy cattle.
AB  - During a 10-month period in 1999, 994 serum and tissue samples were collected
      from dairy cows at slaughter in eastern Canada. The sources of these cattle were
      from all four Atlantic Canadian provinces along with some cows from the state of
      Maine. The sera were used to assess the agreement of three commercially available
      ELISAs for Mycobacterium avium subsp. paratuberculosis. Two ELISAs were indirect
      absorbed ELISAs licensed for use in North America, the third was an indirect non
      absorbed ELISA licensed for use in Europe. Overall, there was poor agreement
      between the three ELISAs. The highest and lowest kappa values were 0.33 and 0.18,
      which is fair and poor agreement, respectively. However, when only tissue culture
      positive cattle were compared, the ELISAs had better agreement (kappa=0.37-0.51).
      The proportions of positive tests, however, were significantly different among
      the three ELISAs. The poor agreement among the three ELISAs is as concerning as
      the fact that these tests have low sensitivity. The implications are greatest
      when the tests are used at the cow level to make individual animal decisions,
      which is not the recommended method on the product labels. At the cow level, if
      the result obtained from one ELISA is positive, using a different ELISA in a pre
      clinical animal has a high likelihood of giving a different result due to low
      predictive values of positive test results.

PMID- 16442753
TI  - Identification by single-strand conformational polymorphism analysis of known and
      new mutations of the CYP3A5 gene in a French population.
AB  - The cytochrome P450 3A5 (CYP3A5) has been shown to be highly involved in the
      metabolism of many therapeutic agents. To date, several polymorphisms affecting
      the CYP3A5 gene have been identified but few studies have shown a complete
      description of the variability of the CYP3A5 in the French population. Therefore,
      the extent of CYP3A5 genetic polymorphism was investigated in a French population
      of 114 patients. The screening of the coding region with their intron-exon
      boundaries and the proximal flanking regions was performed using a PCR-SSCP
      strategy. Eighteen polymorphisms were identified, including four new mutations.
      They correspond to -19 T>C upstream of the exon 1, 7360 T>C in intron 4, 12991
      T>C in intron 5 and 29788 delG in exon 12. We also identified 13 alleles
      including six new alleles. As expected, the most frequent allelic variant is
      CYP3A5*3, with a frequency of 87% of all alleles. These data confirmed that
      CYP3A5 gene is highly polymorphic. Furthermore, it will be now interesting to
      evaluate the impact of this polymorphism on the pharmacokinetic parameters of
      different drugs.

PMID- 16442754
TI  - Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on
      cellular metabolism at realistic intestinal concentrations.
AB  - Deoxynivalenol (DON) is a mycotoxin of the trichothecenes family to which human
      exposure levels can be high. Epidemiological studies suggest a link between DON
      and gastrointestinal illness. We investigated the interaction of DON with Caco-2
      cells, a widely used in vitro model of the human intestinal barrier. The apical
      to basolateral (absorption) and basolateral to apical (excretion) transports of
      DON were found strictly proportional to both the initial concentration and the
      duration of the incubation. The absorption and excretion mean rates were similar
      to those of mannitol and were increased in the presence of EGTA, a calcium
      chelator. These data suggest that DON crosses the intestinal mucosa by a
      paracellular pathway through the tight junctions although some passive
      transcellular diffusion may not be ruled out. The DON transport was not affected
      by P-glycoprotein (PgP) or multidrug resistance-associated proteins (MRPs)
      inhibitors. A prolonged exposure to DON provokes the phosphorylation of the
      mitogen-activated protein kinases (MAPKs) Erk1/2, p38 and SAPK/JNK, as well as a
      decrease of the transepithelial resistance, suggesting that DON could trigger
      intestinal inflammation. These data imply that a chronic exposure to DON
      contaminated foods may negatively affect human health by altering the intestinal
      mucosa integrity and by inducing the MAPKs implicated in inflammation.

PMID- 16442755
TI  - Zinc(II) phthalocyanine loaded PLGA nanoparticles for photodynamic therapy use.
AB  - Sophisticated delivery systems, such as nanoparticles, represent a growing area
      in biomedical research. Nanoparticles (Np) were prepared using a solvent emulsion
      evaporation method (SEEM) to load zinc(II) phthalocyanine (ZnPc). Np were
      obtained using poly (D,L latic-co-glycolic acid) (PLGA). ZnPc is a second
      generation of photoactive agents used in photodynamic therapy. ZnPc loaded PLGA
      nanoparticles were prepared by SEEM, characterized and available in cellular
      culture. The process yield and encapsulation efficiency were 80 and 70%,
      respectively. The nanoparticles have a mean diameter of 285 nm, a narrow size
      distribution with polydispersive index of 0.12, smooth surface and spherical
      shape. ZnPc loaded nanoparticles maintains its photophysical behavior after
      encapsulation. Photosensitizer release from nanoparticles was sustained with a
      moderate and burst effect of 15% for 3 days. The photocytotoxicity of ZnPc loaded
      PLGA Np was evaluated on P388-D1 cells what were incubated with ZnPc loaded Np (5
      microM) by 6h and exposed to red light (675 nm) for 120 s, and light dose of 30
      J/cm(2). After 24h of incubation, the cellular viability was determined,
      obtaining 61% of cellular death. All the physical-chemical, photophysical and
      photobiological measurements performed allow us conclude that ZnPc loaded PLGA
      nanoparticles is a promising drug delivery system for photodynamic therapy.

PMID- 16442756
TI  - Synthesis and transdermal properties of acetylsalicylic acid and selected esters.
AB  - The primary aim of this study was to determine the transdermal penetration of
      acetylsalicylic acid and some of its derivatives, to establish a correlation, if
      any, with selected physicochemical properties and to determine if transdermal
      application of acetylsalicylic acid and its derivatives will give therapeutic
      drug concentrations with respect to transdermal flux. Ten derivatives of
      acetylsalicylic acid were prepared by esterification of acetylsalicyloyl chloride
      with ten different alcohols. The experimental aqueous solubility, logD and
      transdermal flux values were determined for acetylsalicylic acid and its
      derivatives at pH 4.5. In vitro penetration was measured through excised female
      human abdominal skin in diffusion cells. The experimental aqueous solubility of
      acetylsalicylic acid (6.56 mg/ml) was higher than that of the synthesised
      acetylsalicylate derivatives (ranging from 1.76 x 10(-3) to 3.32 mg/ml), and the
      logD of acetylsalicylic acid (-0.85) was lower than that of its derivatives
      (ranging from -0.25 to 1.95). There was thus an inverse correlation between the
      aqueous solubility data and the logD values. The experimental transdermal flux of
      acetylsalicylic acid (263.83 nmol/cm(2)h) was much higher than that of its
      derivatives (ranging from 0.12 to 136.02 nmol/cm(2)h).

PMID- 16442757
TI  - Alginate microspheres prepared by internal gelation: development and effect on
      insulin stability.
AB  - Recombinant human insulin was encapsulated within alginate microspheres by the
      emulsification/internal gelation technique with the objective of preserving
      protein stability during encapsulation procedure. The influence of process and
      formulation parameters was evaluated on the morphology and encapsulation
      efficiency of insulin. The in vitro release of insulin from microspheres was
      studied under simulated gastrointestinal conditions and the in vivo activity of
      protein after processing was assessed by subcutaneous administration of extracted
      insulin from microspheres to streptozotocin-induced diabetic rats. Microspheres
      mean diameter, ranging from 21 to 287 microm, decreased with the internal phase
      ratio, emulsifier concentration, mixer rotational speed and increased with
      alginate concentration. Insulin encapsulation efficiency, near 75%, was not
      affected by emulsifier concentration, mixer rotational speed and zinc/insulin
      hexamer molar ratio but decreased either by increasing internal phase ratio and
      calcium/alginate mass ratio or by decreasing acid/calcium molar ratio and
      alginate concentration. A high insulin release, above 75%, was obtained at pH 1.2
      and under simulated intestinal pH a complete dissolution of microspheres
      occurred. Extracted insulin from microspheres decreased hyperglycemia of diabetic
      rats proving to be bioactive and showing that encapsulation in alginate
      microspheres using the emulsification/internal gelation is an appropriate method
      for protein encapsulation.

PMID- 16442759
TI  - The hypotensive mechanisms for the aqueous stem bark extract of Musanga
      cecropioides in Sprague-Dawley rats.
AB  - The present study was designed to evaluate the hypotensive properties and the
      mechanisms of action of the stem bark aqueous extract of Musanga cecropioides
      R.Br. Apud Tedlie (MCW) in anesthetized rats of Sprague-Dawley strain, through an
      invasive direct blood pressure measuring procedure. Thirty adult rats, weighing
      150-230 g, were grouped into five groups of six rats each. The effects of the
      intravenous graded doses (0.0005-0.05 mg/kg) of the extract on the blood pressure
      indices were investigated. Its underlying mechanisms were also studied using
      additional five groups of rats. The results showed that the extract caused a dose
      dependent fall in the systolic blood pressure (SBP), diastolic blood pressure
      (DBP), mean arterial pressure and heart rate of the rats. Bilateral carotid
      artery occlusion (BCO) caused a reflex increase in mean arterial pressure and
      heart rate which were significantly attenuated by the extract injection.
      Angiotensin Converting Enzyme (ACE) blockade with 5 mg/kg of Captopril and
      cholinergic blockade with 0.2 mg/kg of atropine significantly attenuated the
      hypotensive response to MCW. However, the pattern of MAP fall in rats pretreated
      with a combination of Promethazine (1 mg/kg) and Cimetidine (15 mg/kg) was not
      significant. The results of the study was able to demonstrate dose dependent
      hypotensive effect of MCW and that its vasorelaxant effects may be through
      inhibition of sympathetic, cholinergic control of the arterial pressure and most
      significantly through ACE blockade. However, the phytochemical, elemental and
      toxicological studies of this potential antihypertensive still needed to be
      investigated.

PMID- 16442758
TI  - The choice of a suitable oligosaccharide to prevent aggregation of PEGylated
      nanoparticles during freeze thawing and freeze drying.
AB  - In a previous study we have shown that the oligosaccharide inulin can prevent
      aggregation of poly(ethylene glycol) (PEG) coated plasmid DNA/cationic liposome
      complexes ("PEGylated lipoplexes") during freeze thawing and freeze drying
      [Hinrichs et al., 2005. J. Control. Release 103, 465]. By contrast, dextran
      clearly failed as stabilizer. These results were ascribed to the fact that inulin
      and PEG are compatible while dextran and PEG are not. In this study the
      stabilizing capacities of inulin and dextran (of various molecular weights)
      during freeze thawing and freeze drying of four different types of nanoparticles,
      each type with different amounts of PEG at their surface, were investigated.
      Freeze drying and freeze thawing of 1,2-dioleoyl-3-trimethylammonium-propane
      (DOTAP)/dioleoyl-phosphatidyl-ethanolamine (DOPE) liposomes and egg phosphatidyl
      choline (EPC)/cholesterol (CHOL) liposomes showed that inulins are excellent
      stabilizers even for highly PEGylated liposomes while (especially higher
      molecular weight) dextrans dramatically lost their stabilizing capacity when
      increasing the degree of PEGylation of the liposomes. The same results were
      obtained for plasmid DNA/DOTAP/DOPE complexes. Finally, both inulin and dextran
      could prevent full aggregation of plasmid DNA/polyethylenimine (PEI) complexes
      independent whether PEI was PEGylated or not. It is concluded that inulins are
      preferred as stabilizers over dextrans for various types of PEGylated
      nanoparticles due to their compatibility with PEG.

PMID- 16442760
TI  - Neuropharmacological effects of an ethanol extract of the Magnolia dealbata Zucc.
      leaves in mice.
AB  - Magnolia dealbata Zucc. is considered to have tranquilizer and anticonvulsant
      properties in Mexican traditional medicine. In the present study we report the
      effects of a crude extract of Magnolia dealbata (30, 100 and 300 mg/kg) on mouse
      central nervous system (CNS). Pharmacological effects were tested on ambulatory
      activity, anti-anxiety response, sodium pentobarbital-induced hypnosis and
      pentylenetetrazole (PTZ)-induced seizures in comparison to honokiol, buspirone,
      ethosuximide and diazepam as corresponding reference drugs. No changes in
      spontaneous locomotor activity were produced posterior to Magnolia dealbata
      administration; however, a significant and dose-dependent diminution in the
      anxiety response was observed in experimental models such as plus-maze, head
      dipping and exploratory rearing tests. Magnolia dealbata not only prolonged the
      time of sodium pentobarbital-induced hypnosis and delayed the onset of PTZ
      induced mioclonus and clonus, but also hindered the presence of tonic seizures
      and avoided mortality. The hypnotic, anxiolytic and anticonvulsant effects
      obtained in these experiments support the hypothesis that Magnolia dealbata
      possesses CNS activity and reinforces the popular use in Mexican traditional
      medicine.

PMID- 16442761
TI  - Molecular identification of Astragalus membranaceus at the species and locality
      levels.
AB  - Astragalus membranaceus (Fisch.) Bunge, a commonly used Chinese medicinal
      material, from certain localities contains more favourable trace elements and
      fewer harmful trace elements than those from other localities. Therefore, there
      is a need to distinguish Astragalus membranaceus from different localities.
      Internal transcribed spacer 1 (ITS1) of the nuclear ribosomal RNA gene of 23
      Astragalus membranaceus samples were sequenced to confirm the species of the
      samples. Arbitrarily primed polymerase chain reaction (APPCR) was then used to
      obtain unique fingerprints for each sample using several primers. The presence
      and absence of bands were used for calculating mean similarity indexes among the
      samples. It was found that the Heilongjiang samples were markedly distinguishable
      from samples of other localities. In addition, bands common for samples from the
      same locality were also identified and used to distinguish samples from Neimengu
      and Shanxi. Therefore, Astragalus membranaceus from these provinces, the major
      cultivation places in China, can be differentiated.

PMID- 16442762
TI  - Pro-ejaculatory effect of the aqueous crude extract of cihuapatli (Montanoa
      tomentosa) in spinal male rats.
AB  - In the present study, the pro-sexual effect of the cihuapatli (Montanoa
      tomentosa) and its possible pro-ejaculatory properties in spinal male rats were
      examined. Systemic administration of the aqueous crude extracts of Montanoa
      tomentosa exerted a pro-ejaculatory effect and produced an increase in the number
      of discharges in the ejaculatory motor patterns in the spinal rats. The
      cihuapatli-induced ejaculatory responses included the expression of penile
      erections and penile movements and the potent expulsion of urethral contents and
      in some cases the expulsion of seminal plugs. The cihuapatli-induced ejaculatory
      motor patterns were similar to that obtained after systemic oxytocin. Cihuapatli-
      and oxytocin-induced ejaculatory motor responses and the penile erections and
      movements were abolished by the pre-treatment with hexamethonium, a selective
      oxytocin antagonist. Present data show that the cihuapatli extract acts directly
      at the spinal system in charge of the expression of the ejaculatory motor
      patterns and suggest that the aqueous crude extract exerts its aphrodisiacs
      properties by increasing sexual potency acting as an oxytocic agent.

PMID- 16442764
TI  - Neuropharmacological profile of an ethanol extract of Ruta chalepensis L. in
      mice.
AB  - The effects of an ethanol extract of the aerial parts of Ruta chalepensis on the
      central nervous system (CNS) and LD(50) determination were studied in mice. A
      crude extract was given systemically and its effects were tested on
      pentylenetetrazole (PTZ)-induced seizures, sodium pentobarbital-induced hypnosis,
      exploratory activity, anxiety and nociception. Results from the experimental
      models tested showed: (1) a delay in the onset of seizures and a dose-dependent
      suppression in the tonic phase and mortality induced by PTZ; (2) a prolongation
      of the time of sodium pentobarbital-induced hypnosis; (3) a significant
      attenuation in the anxiety-response and (4) a reduction in the licking time and
      shaking behavior in the formalin-induced nociception test. The sedative-hypnotic
      potentiation, anxiolytic, anticonvulsant and antinociceptive effects suggest that
      Ruta chalepensis induces a depressant activity on the CNS.

PMID- 16442763
TI  - The anti-tumor effects of alkaloids from the seeds of Strychnos nux-vomica on
      HepG2 cells and its possible mechanism.
AB  - To screen the anti-tumor effects of the four alkaloids: brucine, strychnine,
      brucine N-oxide and isostrychnine from the seed of Strychnos nux-vomica, MTT
      assay was used to examine the growth inhibitory effects of these alkaloids on
      human hepatoma cell line (HepG2). Brucine, strychnine and isostrychnine revealed
      significant inhibitory effects against HepG2 cell proliferation, whereas brucine
      N-oxide didn't have such an effect. In addition, brucine caused HepG2 cell
      shrinkage, membrane blebbing, apoptotic body formation, all of which are typical
      characteristics of apoptotic programmed cell death. The results of flow
      cytometric analysis demonstrated that brucine caused dose-dependent apoptosis of
      HepG2 cells through cell cycle arrest at G0/G1 phase, thus preventing cells
      entering S or G2/M phase. Immunoblot results revealed that brucine significantly
      decreased the protein expression level of cyclooxygenase-2, whereas increased the
      expression caspase-3 as well as the caspase-3-like protease activity in HepG2
      cells, suggesting the involvement of cyclooxygenase-2 and caspase-3 in the pro
      apoptotic effects exerted by brucine. Therefore, this paper indicate that the
      major alkaloids present in the seed of Strychnos nux-vomica are effective against
      HepG2 cells proliferation, among which brucine proceed HepG2 cells death via
      apoptosis, probably through the participation of caspase-3 and cyclooxygenase-2.

PMID- 16442765
TI  - Synthesis by-products from the Wacker oxidation of safrole in methanol using rho
      benzoquinone and palladium chloride.
AB  - This paper reports the identification of a number of by-products, which are
      produced during the Wacker oxidation of safrole to 3,4-methylenedioxyphenyl-2
      propanone (MDP2P) using rho-benzoquinone and palladium chloride when methanol is
      utilised as the solvent. Also described is the retrieval of these compounds from
      illicit samples from a clandestine laboratory, which was uncovered in South
      Australia in September 2003.

PMID- 16442766
TI  - Application of pericardial fluid to the analysis of morphine (heroin) and cocaine
      in forensic toxicology.
AB  - In this study opiates (morphine and codeine) and cocaine and its related
      metabolites (benzoylecgonine and cocaethylene) were analyzed in pericardial fluid
      by GC/MS. This is the first study reporting levels of drugs of abuse in this body
      fluid. The analytical method used has been previously validated and then applied
      to 54 drug-related deaths in the Barcelona area (Spain). Median levels were as
      follows: morphine 589ng/ml, range 19-8857 (n=49); codeine 26ng/ml, range 15-343
      (n=35); cocaine 78ng/ml, range 10-220 (n=14), benzoylecgonine 742ng/ml, range 20
      3386 (n=15), and cocaethylene 36ng/ml, range 9-100 (n=13). In addition, a
      comparative study of the concentration of opiates and cocaine in pericardial
      fluid by both semi-quantitative EMIT d.a.u. and GC/MS (used as reference) was
      performed. Fairly good correlations for opiates (r=0.905) and cocaine (r=0.859)
      were found; however, the consistently low results of EMIT in the analysis of
      cocaine comparing to GC/MS could be caused by matrix effect. In spite of that, it
      raises the possibility of using the immunoassay as a preliminary technique in
      forensic toxicology.

PMID- 16442767
TI  - [Bilateral emphysematous pyelonephritis cured by medical therapy alone].
AB  - Emphysematous pyelonephritis is a necrotizing renal infection characterized by
      bacterial gas production in the renal and perirenal area. It is a rare infection
      diagnosed in diabetic patients in most cases. Emphysematous pyelonephritis has a
      high mortality rate. We herein report one case of bilateral emphysematous
      pyelonephritis managed by medical therapy alone.

PMID- 16442770
TI  - Image quality performance of liquid crystal display systems: influence of display
      resolution, magnification and window settings on contrast-detail detection.
AB  - The aim of this study was to investigate the combined effects of liquid crystal
      display (LCD) resolution, image magnification and window/level adjustment on the
      low-contrast performance in soft-copy image interpretation in digital radiography
      and digital mammography. In addition, the effect of a new LCD noise reduction
      mechanism on the low-contrast detectability was studied. Digital radiographs and
      mammograms of two dedicated contrast-detail phantoms (CDRAD 2.0 and CDMAM 3.4)
      were scored on five LCD devices with varying resolutions (1-3- and 5-megapixel)
      and one dedicated 5-megapixel cathode ray tube monitor. Two 5-megapixel LCDs were
      included. The first one was a standard 5-megapixel LCD and the second had a new
      (Per Pixel Uniformity) noise reduction mechanism. A multi-variate analysis of
      variance revealed a significant influence of LCD resolution, image magnification
      and window/level adjustment on the image quality performance assessed with both
      the CDRAD 2.0 and the CDMAM 3.4 phantoms. The interactive adjustment of
      brightness and contrast of digital images did not affect the reading time,
      whereas magnification to full resolution resulted in a significantly slower soft
      copy interpretation. For digital radiography applications, a 3-megapixel LCD is
      comparable with a 5-megapixel CRT monitor in terms of low-contrast performance as
      well as in reading time. The use of a 2-megapixel LCD is only warranted when
      radiographs are analysed in full resolution and when using the interactive
      window/level adjustment. In digital mammography, a 5-megapixel monitor should be
      the first choice. In addition, the new PPU noise reduction system in the 5
      megapixel LCD devices provides significantly better results for mammography
      reading as compared to a standard 5-magapixel LCD or CRT. If a 3-megapixel LCD is
      used in mammography setting, a very time-consuming magnification of the digital
      mammograms would be necessary.

PMID- 16442768
TI  - Improved vessel morphology measurements in contrast-enhanced multi-detector
      computed tomography coronary angiography with non-linear post-processing.
AB  - Multi-detector computed tomography (MDCT) permits detection of coronary plaque.
      However, noise and blurring impair accuracy and precision of plaque measurements.
      The aim of the study was to evaluate MDCT post-processing based on non-linear
      image deblurring and edge-preserving noise suppression for measurements of plaque
      size. Contrast-enhanced MDCT coronary angiography was performed in four subjects
      (mean age 55 +/- 5 years, mean heart rate 54 +/- 5 bpm) using a 16-slice scanner
      (Siemens Sensation 16, collimation 16 x 0.75 mm, gantry rotation 420 ms, tube
      voltage 120 kV, tube current 550 mAs, 80 mL of contrast). Intravascular
      ultrasound (IVUS; 40 MHz probe) was performed in one vessel in each patient and
      served as a reference standard. MDCT vessel cross-sectional images (1 mm
      thickness) were created perpendicular to centerline and aligned with
      corresponding IVUS images. MDCT images were processed using a deblurring and edge
      preserving noise suppression algorithm. Then, three independent blinded observers
      segmented lumen and outer vessel boundaries in each modality to obtain vessel
      cross-sectional area and wall area in the unprocessed MDCT cross-sections, post
      processed MDCT cross-sections and corresponding IVUS. The wall area measurement
      difference for unprocessed and post-processed MDCT images relative to IVUS was
      0.4 +/- 3.8 mm2 and -0.2 +/- 2.2 mm2 (p < 0.05), respectively. Similarly, Bland
      Altman analysis of vessel cross-sectional area from unprocessed and post
      processed MDCT images relative to IVUS showed a measurement difference of 1.0 +/-
      4.4 and 0.6 +/- 4.8 mm2, respectively. In conclusion, MDCT permitted accurate in
      vivo measurement of wall area and vessel cross-sectional area as compared to
      IVUS. Post-processing to reduce blurring and noise reduced variability of wall
      area measurements and reduced measurement bias for both wall area and vessel
      cross-sectional area.

PMID- 16442771
TI  - Determination of rabeprazole enantiomers and their metabolites by high
      performance liquid chromatography with solid-phase extraction.
AB  - Here, we describe the development of a rapid, simple and sensitive high
      performance liquid chromatography (HPLC) method for the simultaneous quantitative
      determination of rabeprazole enantiomers (1a,b) and their metabolites,
      rabeprazole-thioether (2) and rabeprazole sulfone (3), in human plasma. Analytes
      and the internal standard (omeprazole-thioether) were separated using a mobile
      phase of 0.5 M NaClO4-acetonitrile (6:4, v/v) over a Chiral CD-Ph column.
      Analysis required only 100 microl of plasma and involved solid-phase extraction
      with an Oasis HLB cartridge, which gave high recovery (>91.8%) with good
      selectivity for all analytes. The lower limit of quantification was 5 ng/ml for
      analytes 1a, 1b and 3 and 10 ng/ml for 2. Linearity of this assay was determined
      to lie between 5 and 1000 ng/ml for 1a, 1b and 3 and 10 and 1000 ng/ml for 2
      (r2>0.982 of the regression line). Inter- and intra-day coefficients of variation
      were less than 7.8% and accuracies were within 8.4% over the linear range for all
      analytes. Our results indicate that this method is applicable to the simultaneous
      monitoring of plasma levels of rabeprazole enantiomers and associated metabolites
      in human plasma.

PMID- 16442772
TI  - The relation between ultrasonographic observations in the oviduct and plasma
      progesterone, luteinizing hormone and estradiol during the egg laying cycle in
      ostriches.
AB  - In this study we investigated the temporal relationship between ovulation, egg
      formation, oviposition and the changes in plasma concentrations of progesterone,
      luteinizing hormone and estradiol-17beta during the egg laying cycle in farmed
      ostriches. In 10 egg-producing birds, transcutaneous ultrasound scanning was
      performed at 3h intervals and blood sampling at hourly intervals during a period
      of at least 48h (one egg laying cycle). In hens (n=8) that ovulated during the
      observational period, the ovulated egg was first detected 2h after oviposition;
      thus, ovulation occurred shortly after oviposition in all birds. During the
      period between two consecutive ovipositions, the developing egg remained for 9h
      in the proximal part (infundibulum, magnum or isthmus) and for 39h in the distal
      part of the oviduct (uterus). In ovulating hens, plasma progesterone
      concentrations showed a characteristic and consistent profile: from basal levels
      of around 0.1ng/ml concentrations started to increase 12h before oviposition,
      reached an average maximum of 3.5ng/ml at 3h before oviposition and returned to
      basal levels 3h and 30min after oviposition. Changes in plasma luteinizing
      hormone and estradiol-17beta concentrations showed comparable patterns of
      elevation and decline relative to the timing of oviposition and ovulation.
      However, variation in their individual basal concentrations was generally larger
      and peak values were less conspicuous than those of progesterone. In non
      ovulating hens (n=2) neither progesterone, nor luteinizing hormone nor estradiol
      17beta showed elevations to peak concentrations before oviposition. These data
      demonstrate that during the egg laying cycle of ostriches, events such as
      ovulation, egg development and oviposition evolve according to a rather strict
      time schedule, and that progesterone, luteinizing hormone and estradiol-17beta
      reach peak concentrations shortly before ovulation. Additionally, our findings
      also show that on-farm ultrasound scanning is a useful technique to discriminate
      between ovulating and non-ovulating hens.

PMID- 16442774
TI  - DNA tracts composed of only two bases concentrate in gene promoters.
AB  - We have previously shown that long DNA tracts composed of only two of the bases
      ("binary DNA") are highly overrepresented in sequenced eukaryotic genomes. Here
      we examine gene promoter regions, by superposing all genes in a chromosome at
      their transcription start sites. We find that of the four motifs made of two
      bases, three are concentrated in gene promoters: Purine/pyrimidine tracts are
      highly overrepresented in the promoters of yeast chromosome IV, in Caenorhabditis
      elegans chromosome I, in Arabidopsis thaliana chromosome 2, and in human
      chromosomes 14, 21, and 22 (a subset). AT-rich tracts (W tracts) are enriched in
      the same chromosomes, as well as in Drosophila melanogaster chromosome 2R and in
      an archeon, M. jannaschii. A third motif, K.M tracts, shows some concentration in
      D. melanogaster promoters. A propensity of binary DNA to unwind is proposed to
      explain the high presence of the two-base motifs in gene promoters.

PMID- 16442773
TI  - Modulation of cadmium chloride toxicity by sulphur amino acids in hepatoma cells.
AB  - Cadmium is a toxic metal and no effective antidote exists at present. The aim of
      this study was to examine whether sulphur amino acids, involved in glutathione
      synthesis, can modulate cadmium toxicity in vitro. Two hepatoma cell lines (HepG2
      and HTC cells) were exposed to cadmium chloride (0-100 microM) for 8h in control
      media or in media containing 1mM of homocysteine, cysteine or cystathionine. Cell
      viability was then assessed with the neutral red assay. In order to assess the
      mechanism by which homocysteine and cysteine modulate cadmium toxicity their
      ability to scavenge reactive oxygen species was determined as well as the
      potential to increase intracellular glutathione levels. The ability of the
      sulphur amino acids to prevent cadmium uptake by HTC and HepG2 cells was also
      assessed. The results indicate that homocysteine and cysteine protect efficiently
      both cell lines from cadmium chloride toxicity whereas cystathionine protects
      efficiently HTC cells but not HepG2 cells. This effect was shown to be dependent
      on the dose of each amino acid and increased protection from cadmium was observed
      with increasing concentrations of homocysteine and cysteine. Both amino acids
      prevented the formation of reactive oxygen species only when they were
      administered together with cadmium chloride. In addition homocysteine and
      cysteine did not increase intracellular glutathione levels. The results indicate
      that the mechanism by which sulphur amino acids protect from cadmium toxicity in
      vitro is due to the reduced uptake of the metal by the cells possibly by direct
      binding to the -SH group of the amino acids.

PMID- 16442775
TI  - Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a
      novel protein, NM23-LV.
AB  - NM23-H1 and NM23-H2 are neighboring genes on chromosome 17q. They encode
      nucleoside diphosphate kinases that have additional roles in signal transduction,
      transcription, and apoptosis. NM23-H1 expression is a strong marker for prognosis
      and metastatic behavior in many tumor types. A new bioinformatic tool,
      TranscriptView, identified read-through transcripts that start in the NM23-H1
      gene and continue in the neighboring NM23-H2 gene. Splicing results in a
      transcript containing exons 1 to 4 of NM23-H1 and exons 2 to 5 of NM23-H2. The
      resulting mRNA encodes a novel and long variant of the NM23 protein family, NM23
      LV, which contains part of NM23-H1 and the complete NM23-H2 protein. The
      transcript was amplified and sequenced from two neuroblastoma cell lines,
      confirming the presence of the predicted NM23-LV mRNA in vivo. Tissue analysis
      showed that NM23-LV is ubiquitously expressed, with the exception of the kidney.
      Neuroblastoma tumors show high-level expression of NM23-H1 and-H2 as well as NM23
      LV mRNA. In neuroblastoma cells, the NM23-LV protein has mainly a cytoplasmic
      localization, but some nuclear staining was observed as well.

PMID- 16442777
TI  - The evaluation of benign glottic lesions: rigid telescopic stroboscopy versus
      suspension microlaryngoscopy.
AB  - Rigid telescopic strobo-video-laryngoscopy (RTS) is a primary clinical assessment
      methodology in the office evaluation of benign glottic lesions. However,
      diagnostic observations can be made only at the time of suspension
      microlaryngoscopy (SML). The records of 100 consecutive patients undergoing
      microlaryngoscopy for benign glottic lesions were retrospectively reviewed. Nine
      of 100 patients were found to have additional glottic lesions during SML. Sixteen
      additional lesions were noted in these nine patients. Fifteen of 16 lesions were
      sulci and/or mucosal bridges. Forty-five percent (4/9) of the patients with
      additional lesions underwent a management change intraoperatively. Three patients
      underwent additional surgical dissection, and one underwent less dissection than
      was planned. The discrepancy in diagnosis between rigid telescopic strobo-video
      laryngoscopy and suspension microlaryngoscopy highlights certain key points: (1)
      During office endoscopy, tangential views of the medial surface of the glottis
      limit the diagnostic sensitivity. (2) Sulci and mucosal bridges are most subject
      to this limitation. (3) Informed consent should address the potential need for a
      change in intraoperative management. It is advisable to discuss the possibility
      for dissection in both vocal folds, even if a unilateral lesion is observed in
      the office. (4) Microlaryngoscopy is the final diagnostic step in the evaluation
      of glottic pathology. Meticulous inspection and palpation of the glottis are
      recommended during SML.

PMID- 16442776
TI  - Inhaled corticosteroids: hazardous effects on voice-an update.
AB  - Inhaled corticosteroids (ICS) have become the prevalent treatment in asthmatics.
      Hazards to voice are under-recognized. A total of 38 patients with voice
      complaints associated with the use of ICS were assessed by 79
      strobovideolaryngoscopy (SVL) examinations, 24 single and 14 multiple SVL.
      Hoarseness and dysphonia were the primary reasons for referral. The ICS initially
      used most frequently was Advair Diskus (fluticasone propionate and salmeterol
      inhalation powder-[IP]) in 22 patients, followed by Flovent (fluticasone
      propionate inhalation aerosol-pressurized metered-dose inhaler-[PMDI]) in 11.
      Duration of ICS usage varied from 2 weeks to 4-5 years. Higher dosage and
      frequency of use exacerbated problems. Hazards to voice previously unrecognized
      by real-time indirect mirror or fiberoptic laryngoscopy were identified by
      meticulous attention to SVL abnormalities. There was essentially no difference in
      occurrence of abnormalities whether analyzed from the perspective of the initial
      38 or all 79 examinations. These included abnormal mucosal wave
      symmetry/periodicity (76-63%), phase closure (74-63%), glottic closure (63-59%),
      mucosal wave amplitude/magnitude (50-35%), supraglottic hyperactivity (39-25%),
      mucosal quality (34-34%), and glottic plane (10-5%). Candidiasis of the larynx
      was infrequently observed. Fluticasone ICS were a cause of steroid inhaler
      laryngitis, and the best treatment was their avoidance or cessation. Further
      prospective studies ideally might include SVL documented as a pretherapy baseline
      and then repeated in each ICS patient who developed hoarseness/dysphonia.

PMID- 16442778
TI  - Fyn kinase acts upstream of Shp2 and p38 mitogen-activated protein kinase to
      promote chemotaxis of mast cells towards stem cell factor.
AB  - The c-Kit receptor protein-tyrosine kinase plays a critical role in the
      differentiation, growth and survival of mast cells. Binding of its ligand stem
      cell factor (SCF), induces c-Kit dimerization, autophosphorylation, and
      recruitment of signaling proteins. The juxtamembrane sequence of c-Kit contains
      recruitment sites for the Src family kinases Fyn and Lyn, as well as Shp1 and
      Shp2 protein-tyrosine phosphatases. To characterize the role of Fyn in c-Kit
      signaling, we generated bone marrow-derived mast cells (BMMCs) from wild-type and
      Fyn knock-out mice. In contrast with previous studies of Lyn-deficient BMMCs, SCF
      treatment of Fyn-deficient BMMCs revealed no overt defects in the overall pattern
      of tyrosine phosphorylation, phosphatidylinositol 3' kinase recruitment to c-Kit,
      or phosphorylation of Stat3 transcription factor. However, Fyn-deficient mast
      cells showed a significant reduction in phosphorylation of Shp2 phosphatase and
      p38 mitogen-activated protein kinase. Defects in Shp2 and p38 phosphorylation
      were restored in Fyn-deficient mast cells transduced with a Fyn-expressing
      retrovirus (Fyn-rescue). Fyn-deficient BMMCs displayed reduced chemotaxis towards
      SCF, and this defect was corrected in Fyn-rescue cells. This study provides
      evidence that recruitment of both Shp2 and Fyn to juxtamembrane sites in c-Kit
      results in Shp2 phosphorylation, downstream signaling to p38 mitogen-activated
      protein kinase, and enhanced chemotaxis of mast cells.

PMID- 16442779
TI  - Reconstruction of large defects postmandibulectomy for oral cancer using plates
      and myocutaneous flaps: a long-term follow-up.
AB  - A series of 28 consecutive cases of mandibular reconstruction by means of
      reconstructive plates and myocutaneous flaps were reviewed. In all cases
      mandibular resection was indicated for treatment of squamous cell carcinoma of
      the oral cavity: 25 pelviglossomandibulectomies (resulting in large defects from
      the angle of the mandible), 2 Commando operations (resulting in lateral defects)
      and 1 anterior sectional mandibulectomy (resulting in an anterior defect). Tumour
      stages were T1-T2 (4 cases) and T3-T4 (24 cases). Success was defined as plate
      maintenance 6 months' postoperatively/postradiotherapy. The overall success rate
      was 32.2%. Lateral-centre-lateral (L-C-L) defects had 32% success, L (lateral)
      defects had 50% success and in the single case of a C (centre) defect, the plate
      was not maintained. Stainless steel reconstruction plates showed a similar
      success rate as titanium plates (30% versus 34%). In cases not submitted to
      radiotherapy there were more maintained plates than in cases that received
      radiotherapy (45.5% versus 23.6%). Reconstruction plates are not effective in
      bridging large defects of the resected mandible. Only in selected cases that are
      not eligible for microvascular free flaps should plates and myocutaneous flaps be
      considered as an option for mandibular reconstruction.

PMID- 16442780
TI  - No association of complexin1 and complexin2 genes with schizophrenia in a
      Japanese population.
AB  - Several investigations suggest that complexin may be a schizophrenia
      susceptibility factor. We conducted a genetic association analysis between
      complexin genes (CPLX1 and CPLX2) and schizophrenia in Japanese patients (377
      cases and 341 controls). Ten and eleven haplotype-tagging (ht)SNPs in CPLX1 and
      CPLX2, respectively, were selected. Only one htSNP (rs930047 in CPLX2) in allele
      wise analysis showed significance, and even this disappeared with an increased
      sample size (563 cases and 519 controls: P = .757). Haplotype-wise analysis
      showed a weak association with a combination of htSNPs in CPLX2 (P = .0424), but
      this may be a result of type I error due to multiple testing. Our results suggest
      that complexin genes do not play a major role in schizophrenia in Japanese
      patients.

PMID- 16442781
TI  - Differential effects of long-term treatment with typical and atypical
      antipsychotics on NGF and BDNF levels in rat striatum and hippocampus.
AB  - The results of mostly short-term treatment studies in human patients and animals
      suggest that second-generation antipsychotics (SGAs) such as risperidone (RISP)
      and olanzapine (OLZ) compared to first-generation antipsychotics (FGAs) such as
      haloperidol (HAL) and chlorpromazine (CPZ) have neuroprotective effects. The
      animal studies indicate that these effects are probably mediated through
      increased expression of neurotrophic factors such as nerve growth factor (NGF)
      and brain derived neurotrophic factor (BDNF). However, since antipsychotics are
      commonly used for very long-term treatment periods, particularly in schizophrenic
      patients, it is important to measure the effects of chronic administration of
      antipsychotic drugs on the aforementioned growth factors. This study determined
      the effects of 90- and 180-day treatments with two FGAs, HAL and CPZ, and two
      SGAs, RISP and OLZ, on the levels of NGF and BDNF protein in hippocampus and
      striatum of rat. Furthermore, since a preliminary study showed that 90-day
      treatment of HAL caused significant reductions in the expression of both NGF and
      BDNF the HAL-treated animals were then switched to SGAs for the next 90 days to
      assess the potential for restoration of trophic factor levels. After the 90-day
      treatment, NGF levels in the hippocampus were reduced by 60-70% with HAL or CPZ,
      and by only 25-30% with RISP or OLZ compared to levels with vehicle only. After
      the 180-day treatment, NGF levels were further reduced with HAL, RISP, and OLZ,
      but not with CPZ. The magnitude of the NGF decreases in the striatum was larger
      (70-90%) with all the antipsychotics compared to the hippocampus. However, the
      pattern of BDNF changes in the hippocampus differed significantly from the
      striatum after 90- or 180-day treatment with the antipsychotics. In hippocampus,
      compared to controls, BDNF levels remained unchanged with OLZ both after 90 and
      180 days of treatment. Whereas, larger decreases in BDNF levels were observed
      with HAL or CPZ and intermediate decreases were observed with RISP after 90 days
      of treatment that continued to decline up to 180 days. Furthermore, switching HAL
      animals after 90 days of treatment to either RISP or OLZ for the next 90 days
      significantly restored levels of both NGF and BDNF in both the brain regions.
      These data indicate that SGAs compared to FGAs induce less deleterious effects on
      neurotrophic factor levels in the brain and may also offer ability to reverse the
      more pronounced negative effects of FGAs as well. These data may have significant
      clinical implications for long-term antipsychotic selection as well as the common
      practice of antipsychotic switchover.

PMID- 16442782
TI  - Revisiting cycloid psychosis: a case of an acute, transient and recurring
      psychotic disorder.
AB  - We report a case of recurrent psychosis, spanning decades, with full inter
      episode recovery and minimal functional impairment. While it is difficult to
      classify this disorder using DSM IV-TR criteria, Leonhard and others have
      described a 'cycloid psychosis' that correlates well with the phenomenology and
      course of this case. We believe this may represent a subset within the ICD-10
      category of 'acute and transient psychotic disorders'. While this disorder, of
      unknown incidence, is not well reported in the U.S., it is worthy of further
      investigation and clinical attention given its generally favorable prognosis and
      potentially distinct pathophysiology and treatment.

PMID- 16442783
TI  - The 15N chemical shifts in mixed NB2Si and NBSi2 environments of Si3B3N7--a
      theoretical investigation.
AB  - Nuclear magnetic resonance (NMR) chemical shifts in solids may be calculated by
      ab initio methods approximating the solid state by molecular clusters. We
      employed this technique to obtain estimates of (15)N chemical shifts in NB(2)Si
      and NBSi(2) environments in the solid state. Such nitrogen environments are found
      in amorphous (Si/B/N-)ceramics which exhibit very interesting features such as
      high thermal and mechanical stability. We based our calculations on cutouts of
      hypothetical Si(3)B(3)N(7) crystals suggested by Kroll and Hoffmann [Silicon
      boron nitrides: hypothetical polymorphs of Si(3)B(3)N(7), Angew. Chem. Int. Ed.
      37 (1998) 2527]. Taking the systematic errors of our calculations into account we
      expect the chemical shifts in NBSi(2) environments around -293+/-5ppm. Chemical
      shifts in NB(2)Si environments are expected at -272+/-6ppm. The range of the
      calculated chemical shifts in NBSi(2) environments coincides with experimental
      chemical shifts in molecular compounds. Experimental chemical shifts of NB(2)Si
      nitrogen in molecules appear at lower field than our calculated chemical shifts
      in the solid state.

PMID- 16442784
TI  - siRNA--getting the message out.
AB  - The recent observation that potent and sequence-specific gene silencing by
      injection of double-stranded RNA (dsRNA) has sparked the phenomenon known as "RNA
      interference" (RNAi) and has enabled the gene-specific knockdown of drug
      transport proteins and metabolizing enzymes. The application of small interfering
      RNAs (siRNAs) is broad and the potential for use as research tools is now well
      established in vitro. In vivo use is still a challenge that is primarily focused
      on the difficulty of delivering siRNAs to target cells. The potential use of
      siRNAs as therapeutic agents is also exciting and holds great promise for future.
      For the study of drug transporter function in absorption, distribution,
      metabolism and excretion (ADME) and in the treatment of diseases, siRNA offers a
      way to gather interpretable mechanistic data-a distinct advantage over the use of
      "specific" chemical inhibitors. This mini review provides background information
      on siRNA as well as examples of the use of siRNA as applied to drug transporters.

PMID- 16442785
TI  - A role for the protein phosphatase 2B in altered hippocampal synaptic plasticity
      in the aged rat.
AB  - Synaptic plasticity following NMDA application on hippocampal slices from young
      (3-5 months) and aged (24-27 months) rats was compared. In young rats, NMDA (20
      microM) induced opposite effects depending on the duration of the application. A
      short (1 min) or long (5 min) application induced a long-term depression of
      synaptic activity while a 3 min application induced a potentiation. In aged rats,
      however, NMDA application always induced depression, regardless of the duration.
      To identify mechanisms which could explain the difference observed between young
      and aged rats, we explored changes in NMDA receptor activation and changes in
      kinase/phosphatase balance. We first demonstrate that the potentiation present in
      slices from young rats was not restored in aged rats by exogenous application of
      the co-agonist of NMDA receptor d-serine (which compensates for the changes in
      NMDAR activation seen in aged rats). This suggested that alterations in synaptic
      plasticity activation mainly involve intracellular mechanisms. We next showed
      that the participation of the kinases PKA and CaMKII in the NMDA-induced
      potentiation in young rats is negligible. Finally, we determined the consequences
      of phosphatase inhibition in aged rats. Incubation of slices in okadaic acid (a
      PP1/PP2B antagonist) did not affect the depression induced by a 3min NMDA
      application in aged rats. The PP2B antagonist FK506 restored potentiation in aged
      rats (3 min NMDA application). In hippocampal neurons from aged rats, a
      depression is always observed, suggesting a preferential activation of PP2B by
      NMDA in these neurons.

PMID- 16442786
TI  - Long term recordings with microelectrode arrays: studies of transcription
      dependent neuronal plasticity and axonal regeneration.
AB  - Substrate integrated microelectrode arrays (MEAs) offer an alternative to
      classical electrophysiological methods like the patch clamp technique for
      recording the electrical activity from cells and tissue of neuronal or cardiac
      origin. Since its introduction 30 years ago, this technology has made possible
      the repeated simultaneous recording from multiple sites in a non-invasive manner.
      The MEA technology can be applied to any electrogenic cells or tissue (i.e.,
      central and peripheral neurons, heart cells, and muscle cells), either as
      cultures or acute cell or slice preparations. The combination of culture
      techniques and MEAs offers the possibility to monitor the activity of a designed
      specimen over extended periods of time, up to several months. Furthermore,
      recording the electrical activity of distributed regions of a preparation yields
      information on spatial effects that might go undetected with other recording
      methods. Development, plasticity, and regeneration are examples of applications
      that could especially benefit from long term monitoring of neuronal activity, as
      they concern processes that develop over extended periods of time. Here we
      highlight recent MEA studies on signal regulation of neuronal network behavior
      and axonal regeneration. We illustrate the use of MEAs to study long term
      potentiation (LTP) and summarize the advantages of MEA technology over
      traditional electrophysiological methods for studies aimed at understanding the
      transcription-dependent late phase of plasticity.

PMID- 16442787
TI  - [Afebrile seizures in gastroenteritis: a Japanese peculiarity].
AB  - Febrile seizures appearing during acute gastroenteritis have been described in
      japanese populations. These convulsions are not related to clinical signs of
      dehydration or electrolyte disorder. This entity was called CwG, benign
      Convulsions with mild Gastroenteritis. We report the case of a 19 month-old
      japanese boy who presented with a CwG. We described the characteristic clinical
      features of this entity and we reviewed the cases reported in literature. The
      evolution of the CwG is always simple without relapse or side effects. Better
      understanding will help pediatricians make more accurate diagnosis and avoid
      treatment even though initial signs might be severe.

PMID- 16442788
TI  - [Paravertebral streptococcal myositis complicated by an epidural abscess in a 5
      year-old girl].
AB  - CASE REPORT: A 5-year-old girl was hospitalised for fever, abdominal and lumbar
      pain, associated with general impairment state and a whitlow. One of the blood
      cultures and CSF grew A beta haemolytic Streptococcus, muscular echography and
      MRI showed paravertebral myositis, which was complicated by an epidural abscess.
      The outcome was good with medical treatment alone. DISCUSSION: Streptococcal
      myositis is a rare and severe skeletal muscle infection caused by A beta
      haemolytic Streptococcus. It is characterized by a muscle necrosis, without
      abscess formation. It has to be distinguished from pyomyositis, usually caused by
      Staphylococcus aureus, where a muscle abscess occurs, which must be treated by
      surgical drainage and antibiotics. Prognosis of this infection is poorer than
      other muscle infections such as pyomyositis, with a high mortality rate. The
      diagnosis is difficult and often delayed. Practitioners should keep in mind this
      diagnosis, even if symptoms are non specific, in front of an undetermined
      infectious syndrome associated with pain, and make an echography or nuclear
      magnetic resonance imaging to confirm the diagnosis.

PMID- 16442789
TI  - Fundamental processes and implications during in situ aeration of old landfills.
AB  - Results of investigations from many old landfills in Germany and Europe indicate
      that significant emissions occur under conventional landfill operating conditions
      (i.e., anaerobic conditions). Significant emissions via the gas phase are
      predicted to last at least three decades after landfill closure, while leachate
      emissions are predicted to continue for many decades, potentially even lasting
      for centuries. When considering the specific type and quality, and quite often
      lack of, protection barriers associated with old landfills, these leachate and
      gas emissions may result in a significant negative impact on the environment.
      However, complete sealing of the landfill only temporarily reduces emissions
      because dry-conservation of the biodegradable waste fraction results, thus not
      allowing any severe reduction in the emission and hazardous potential of the
      landfill to occur. If noticeable damage of the surface capping system occurred in
      these landfills, infiltrating water would restart the interrupted emission
      formation. In contrast, aerobic in situ stabilization by means of low pressure
      aeration attempts to stabilize and modify the inventory of organic matter inside
      the landfill, acting to reduce the emission potential in a more sustainable
      manner. By enabling faster and more extensive aerobic degradation processes in
      the landfill (compared with anaerobic processes), the organics (e.g.,
      hydrocarbons) are degraded significantly faster, resulting in an increased carbon
      discharge via the gas phase, as well as reduced leachate concentrations. Because
      carbon dioxide (CO(2)) is the main compound in the extracted off-gas (instead of
      methane (CH(4)), which dominated under anaerobic landfill conditions), the
      negative impact of diffuse LFG emissions towards an increased global warming
      effect may be significantly lowered. With respect to leachate quality, a
      reduction of organic compounds as well as ammonia-nitrogen can be expected. In
      addition to these positive ecological effects, aerobic in situ stabilization is
      associated with significant cost savings potential due to both quantitative and
      qualitative reductions in the aftercare period. This paper describes the
      fundamental processes and implications of in situ landfill aeration.
      Additionally, possible criteria for defining an endpoint of the active aeration
      process are presented and discussed.

PMID- 16442790
TI  - Carbon and hydrogen isotope fractionation by microbial methane oxidation:
      improved determination.
AB  - Isotope fractionation is a promising tool for quantifying methane oxidation in
      landfill cover soils. For good quantification an accurate determination of the
      isotope fractionation factor (alpha) of methane oxidation based on independent
      batch experiments with soil samples from the landfill cover is required. Most
      studies so far used data analysis methods based on approximations of the Rayleigh
      model to determine alpha. In this study, the two most common approximations were
      tested, the simplified Rayleigh approach and the Coleman method. To do this, the
      original model of Rayleigh was described in measurable variables, methane
      concentration and isotopic abundances, and fitted to batch oxidation data by
      means of a weighted non-linear errors-in-variables regression technique. The
      results of this technique were used as a benchmark to which the results of the
      two conventional approximations were compared. Three types of batch data were
      used: simulated data, data obtained from the literature, and data obtained from
      new batch experiments conducted in our laboratory. The Coleman approximation was
      shown to be acceptable but not recommended for carbon fractionation (error on
      alpha-1 up to 5%) and unacceptable for hydrogen fractionation (error up to 20%).
      The difference between the simplified Rayleigh approach and the exact Rayleigh
      model is much smaller for both carbon and hydrogen fractionation (error on alpha
      1<0.05%). There is also a small difference when errors in both variables (methane
      concentration and isotope abundance) are accounted for instead of assuming an
      error-free independent variable. By means of theoretical calculations general
      criteria, not limited to methane, (13)C, or D, were developed for the validity of
      the simplified Rayleigh approach when using labelled compounds.

PMID- 16442791
TI  - Applying guidance for methane emission estimation for landfills.
AB  - Quantification of methane emission from landfills is important to evaluate
      measures for reduction of greenhouse gas emissions. Both the United Nations and
      the European Union have adopted protocols to ensure quantification of methane
      emission from individual landfills. The purpose of these protocols is to disclose
      emission data to regulators and the general public. Criteria such as timeliness,
      completeness, certainty, comparability, consistency and transparency are set for
      inclusion of emission data in a publicly accessible database. All methods given
      as guidance to landfill operators to estimate landfill methane emissions are
      based on models. In this paper the consequences of applying six different models
      for estimates of three landfills are explored. It is not the intention of this
      paper to criticise or validate models. The modelling results are compared with
      whole site methane emission measurements. A huge difference in results is
      observed. This raises doubts about the accuracy of the models. It also indicates
      that at least some of the criteria previously mentioned are not met for the tools
      currently available to estimate methane emissions from individual landfills. This
      will inevitably lead to compiling and comparing data with an incomparable origin.
      Harmonization of models is recommended. This may not necessarily reduce
      uncertainty, but it will at least result in comparable, consistent and
      transparent data.

PMID- 16442792
TI  - Electrochemical characterization and application of azurin-modified gold
      electrodes for detection of superoxide.
AB  - A novel biosensor for superoxide radical (O(2)(*-)) detection based on
      Pseudomonas aeruginosa azurin immobilized on gold electrode was designed. The
      rate constant of azurin reduction by O(2)(*-) was found to be 10(5)M(-1)s(-1) in
      solution and five times lower, i.e., 0.2 x 10(5)M(-1)s(-1), for azurin coupled to
      gold by 3,3'-dithiobis(sulfosuccinimidylpropionate) (DTSSP). The electron
      transfer rate between the protein and the electrode ranged from 2 to 6s(-1). The
      sensitivity of this biosensor to O(2)(*-) was 6.8 x 10(2)Am(-2)M(-1). The
      response to the interference substances, such as uric acid, H(2)O(2), and
      dimethylsulfoxide was negligible below 10 microM. The electrode was applied in
      three O(2)(*-) generating systems: (i) xanthine oxidase (XOD), (ii) potassium
      superoxide (KO(2)), and (iii) stimulated neutrophil granulocytes. The latter was
      compared with luminol-amplified chemiluminescence. The biosensor responded to
      O(2)(*-) in all three environments, and the signals were antagonized by
      superoxide dismutase.

PMID- 16442793
TI  - Skin cancer in survivors of childhood and adolescent cancer.
AB  - The incidence of basal cell carcinoma (BCC) has been related to ionizing
      radiation, particularly for exposure occurring at young age. In this study, we
      considered the incidence of second skin neoplasms in long-term survivors from
      childhood cancer. We considered second primary cancers occurring among 776
      subjects (436 males, 340 females) with first primary cancer diagnosed before age
      20 years, between 1974 and 2001, in the Swiss Cantons of Vaud and Neuchatel
      (786,000 inhabitants). Five BCC were observed versus 0.43 expected (standardized
      incidence ratio: 11.6, 95% confidence interval: 3.7-27.1). No case of cutaneous
      squamous cell carcinoma, nor of malignant melanoma was observed. The estimated
      radiation doses at 1mm through the skin ranged between 7 and 27 Sv. These data
      confirm that BCC are strongly related to ionizing radiation exposure in
      childhood. All the BCC were located within the radiation field, thus indicating
      that ionizing radiation is the key aetiological factor, even in the absence of
      any meaningful interaction with UV.

PMID- 16442795
TI  - Nitrobenzylcarbamate prodrugs of cytotoxic acridines for potential use with
      nitroreductase gene-directed enzyme prodrug therapy.
AB  - The synthesis, solvolytic behaviour and cytotoxicity of novel 4-nitrobenzyl
      carbamates and carbonates derived from 3-amino-4-hydroxymethylacridine 1 are
      described. Compounds 2 and 6 are both substrates for Escherichia coli
      nitroreductase and the highly active lead structure 1 is liberated upon
      incubation of the two compounds in the presence of NTR and its cofactor NADH.
      Additionally, the cytostatic activity of 2 and 6 against human HT29 colon
      carcinoma cell lines is decreased 80-fold and 360-fold, respectively, indicating
      their suitability and potency as prodrugs for either gene-directed enzyme prodrug
      therapy or antibody-directed enzyme prodrug therapy.

PMID- 16442794
TI  - Discovery of highly selective EP4 receptor agonists that stimulate new bone
      formation and restore bone mass in ovariectomized rats.
AB  - Heptanoic acid lactams, exemplified by 2, were identified as highly selective EP4
      agonists via high throughput screening. Lead optimization led to the
      identification of lactams with a 30-fold increase in EP4 potency in vitro.
      Compounds demonstrated robust bone anabolic effects when administered in vivo in
      rat models of osteoporosis.

PMID- 16442796
TI  - Analogues of N-hydroxycinnamoylphenalkylamides as inhibitors of human melanocyte
      tyrosinase.
AB  - Melanin play a major role in human skin protection and their biosynthesis is
      vital. Due to their color, they contribute to the skin pigmentation. Tyrosinase
      is a key enzyme involved in the first stage of melanin synthesis, catalyzing the
      transformation of tyrosine to l-dopaquinone. The aim of the present study was to
      study molecules able to inhibit melanin synthesis through inhibition of
      tyrosinase and their potential use in treating pigmentation-related disorders. We
      targeted amides obtained from coupling p-hydroxycinnamic acid derivatives with
      phenylalkylamines. The biological activity was evaluated on human melanocytes by
      an assay which measures tyrosine-catalyzed L-Dopa oxidation. The most active
      amides were: trans-N-caffeoyltyramine, N-dihydrocaffeoyltyramine, and trans-N
      dihydro-p-hydroxycinnamoyltyramine which induce complete inhibition at 0.1mM. At
      the latter concentration, kojic acid, which was used as the reference inhibitor,
      was inactive.

PMID- 16442797
TI  - Bickerstaff's brainstem encephalitis: can it recur?
AB  - Bickerstaff's brain-stem encephalitis is usually a monophasic post-viral
      inflammatory illness characterized by progressive ophthalmoplegia, ataxia and
      disturbance of consciousness (or hyper-reflexia). Since the clinical spectrum of
      Bickerstaff encephalitis may overlap with the Miller-Fisher and Guillain-Barre
      syndromes, the presence of anti- GQ1b antibodies and abnormal brain MRI can help
      to support its diagnosis. However, absence of anti-GQ1b antibodies and normal MRI
      do not exclude the diagnosis, which remains based on clinical criteria and
      exclusion of other etiologies. We report a case of recurrent Bickerstaff's
      brainstem encephalitis with no identifiable antecedent illness, and overlapping
      features of Miller Fisher and Guillain-Barre syndromes, in the presence of
      negative anti-GQ1b antibodies and repeatedly normal MRI of the brain.

PMID- 16442799
TI  - 2D Autocorrelation modeling of the negative inotropic activity of calcium entry
      blockers using Bayesian-regularized genetic neural networks.
AB  - Negative inotropic potency of 60 benzothiazepine-like calcium entry blockers
      (CEBs), Diltiazem analogs, was successfully modeled using Bayesian-regularized
      genetic neural networks (BRGNNs) and 2D autocorrelation vectors. This approach
      yielded reliable and robust models whilst by means of a linear genetic algorithm
      (GA) search routine no multilinear regression model was found describing more
      than 50% of the training set. On the contrary, the optimum neural network
      predictor with five inputs described about 84% and 65% variances of 50 randomly
      selected training and test sets. Autocorrelation vectors in the nonlinear model
      contained information regarding 2D spatial distributions on the CEB structure of
      van der Waals volumes, electronegativities, and polarizabilities. However, a
      sensitivity analysis of the network inputs pointed out to the electronegativity
      and polarizability 2D topological distributions at substructural fragments of
      sizes 3 and 4 as the most relevant features governing the nonlinear modeling of
      the negative inotropic potency.

PMID- 16442798
TI  - Persistent popliteal pain derived from cavernous hemangioma involving gracilis
      tendon and tendon sheath.
AB  - Hemangiomas arising from tendon and tendon sheath are rarely reported, and may be
      confused with other lesions of tendons. In this case report, a 19-year-old woman
      was diagnosed with a cavernous hemangioma originating in the left gracilis tendon
      and tendon sheath. When her symptoms initially developed, MRI did not delineate
      the lesion due to the relatively small size of the tumor. Nine years after the
      onset of the patient's complaints of knee pain and swelling, the tumor was
      adequately diagnosed on physical examination and MRI, and was resected with
      complete relief of symptoms.

PMID- 16442800
TI  - Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone
      receptor antagonists.
AB  - Melanin concentrating hormone (MCH) receptor antagonists have been proposed as
      potential treatments of obesity. MCH receptor antagonists with a biphenylamine
      subunit have been reported previously at Schering-Plough. Herein, we report the
      discovery of bicyclo[4.1.0]heptanes as replacements for the middle phenyl ring of
      the biphenylamine moiety in order to eliminate its potential mutagenic liability.
      Structure-activity relationships in this series were found to be very similar to
      those of the original biphenylamine series, suggesting that the two series have
      similar binding modes.

PMID- 16442801
TI  - Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor
      antagonist (E)-8-(3-chlorostyryl)caffeine (CSC).
AB  - The adenosine A2A receptor has emerged as a possible target for the treatment of
      Parkinson's disease (PD). Evidence suggests that antagonism of the A2A receptor
      not only improves the symptoms of the disease but may also protect against the
      underlying degenerative processes. We have recently reported that several known
      adenosine A2A receptor antagonists (A2A antagonists) also are moderate to very
      potent inhibitors of monoamine oxidase B (MAO-B). The most potent among these was
      (E)-8-(3-chlorostyryl)caffeine (CSC), a compound frequently used when examining
      the in vivo pharmacological effects of A2A antagonists. Since MAO-B inhibitors
      are also thought to possess antiparkinsonian properties, dual targeting drugs
      that block both MAO-B and A2A receptors may have enhanced therapeutic potential
      in the treatment of PD. In this study, we prepared selected analogues of CSC in
      an attempt to examine specific structural features that may be important for
      potent MAO-B inhibition. The results of a SAR study established that the potency
      of MAO-B inhibition by (E)-8-styrylcaffeinyl analogues depends upon the van der
      Waals volume (V(w)), lipophilicity (pi), and the Hammett constant (sigma(m)) of
      the substituents attached to C-3 of the phenyl ring of the styryl moiety. Potency
      also varies with substituents attached to C-4 with bulkiness (V(w)) and
      lipophilicity (pi) being the principal substituent descriptors.

PMID- 16442802
TI  - Sarcospan: ultrastructural localization and its relation to the sarcoglycan
      subcomplex.
AB  - Sarcospan is a 25 kDa transmembrane component of dystrophin-associated
      glycoprotein. We generated a rabbit polyclonal antibody against synthetic peptide
      of the N-terminal domain of human sarcospan. Using this antibody we investigated
      the localization of sarcospan and its spacial relation to the components of
      sarcoglycan subcomplex in normal human skeletal myofibers by immunofluorescent
      microscopy and immunogold electron microscopy. In immunofluorescence the reaction
      was observed continuously at the myofiber surface. Ultrastructurally the gold
      signals of rabbit anti sarcospan antibody were present along the muscle plasma
      membrane, mainly at its inside surface. The triple immunogold labeled muscle
      samples showed that the signals of rabbit or sheep polyclonal anti alpha-, beta-,
      gamma- and delta-sarcoglycan antibodies and/or mouse monoclonal anti beta-, gamma
      and delta-sarcoglycan antibodies were located along the muscle plasma membrane,
      and the cluster formation of different two or three sarcoglycan molecules was
      observed. The triple immunogold labeling also revealed that the signal of
      sarcospan molecules are present frequently in doublets and/or triplets with the
      components of sarcoglycan subcomplex, resulting in the cluster formation of
      signals of sarcoglycan and sarcospan molecules. The result of this study showed
      that sarcospan was expressed at the myofiber surface and that sarcospan was
      present in close association with alpha-, beta-, gamma- and delta-sarcoglycans
      and formed a functional unit with sarcoglycan subcomplex.

PMID- 16442803
TI  - Structural insight into interactions between dihydrolipoamide dehydrogenase (E3)
      and E3 binding protein of human pyruvate dehydrogenase complex.
AB  - The 9.5 MDa human pyruvate dehydrogenase complex (PDC) utilizes the specific
      dihydrolipoamide dehydrogenase (E3) binding protein (E3BP) to tether the
      essential E3 component to the 60-meric core of the complex. Here, we report
      crystal structures of the binding domain (E3BD) of human E3BP alone and in
      complex with human E3 at 1.6 angstroms and 2.2 angstroms, respectively. The
      latter structure shows that residues from E3BD contact E3 across its 2-fold axis,
      resulting in one E3BD binding site on the E3 homodimer. Negligible conformational
      changes occur in E3BD upon its high-affinity binding to E3. Modifications of E3BD
      residues at the center of the E3BD/E3 interface impede E3 binding far more
      severely than those of residues on the periphery, validating the "hot spot"
      paradigm for protein interactions. A cluster of disease-causing E3 mutations
      located near the center of the E3BD/E3 interface prevents the efficient
      recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction
      of the PDC catalytic machine.

PMID- 16442804
TI  - Selective defects in channel permeability associated with Cx32 mutations causing
      X-linked Charcot-Marie-Tooth disease.
AB  - The X-linked form of Charcot-Marie-Tooth disease (CMTX) is caused by mutations in
      connexin32 (Cx32), a gap junction protein expressed by Schwann cells where it
      forms reflexive channels that allow the passage of ions and signaling molecules
      across the myelin sheath. Although most mutations result in loss of function,
      several studies have reported that some retain the ability to form homotypic
      intercellular channels. To gain insight into the molecular defect of three
      functional CMTX variants, S26L, Delta111-116 and R220stop, we have used several
      fluorescent tracers of different size and ionic charge to compare their
      permeation properties to those of wild-type Cx32. Although all mutations allowed
      the passage of the dye with the smallest molecular mass, they exhibited a clear
      reduction in the permeability of either one or all of the probes with respect to
      wild-type channels, as assessed by the percentage of injections showing dye
      coupling. These data reveal that a lower size cutoff distinguishes these
      functional CMTX variants from wild-type channels and suggest that this defect may
      be of pathophysiological relevance.

PMID- 16442806
TI  - Modulation of carotenoid biosynthesis during tomato fruit ripening through
      phytochrome regulation of phytoene synthase activity.
AB  - The accumulation of carotenoids greatly influences the quality of ripe tomato
      (Solanum lycopersicum) fruit because these compounds contribute to their color
      and functional food value. The regulatory properties and gene expression of
      phytoene synthase (PSY), a key enzyme involved in carotenoid biosynthesis, was
      analyzed in tomato fruit. PSY activity was detected in the soluble fraction
      showing a time- and a protein-dependent increase in the formation of phytoene
      from geranylgeranyl pyrophosphate (GGPP). The enzyme was stimulated by Mg(2+) and
      ATP, and was inhibited by Tween 20 and Triton X-100. The enzyme followed typical
      Michaelis-Menten kinetics with increasing GGPP. During in vivo studies, pericarp
      discs from breaker stage tomatoes were ripened in darkness (D), or D interrupted
      by daily pulses of red (R) light, or R followed by far red (FR) light. After 14
      days incubation, R-treated discs had accumulated 12 mg carotenoids/100 g fresh
      weight; nearly a 50% increase over D- and R/FR-treated discs. This R/FR
      reversibility of carotenoid accumulation was also observed in PSY activity 8 days
      post breaker, where it showed peak activity. However, this R/FR regulation of PSY
      activity was not reflected in PSY1 transcript levels, suggesting that PSY may be
      subject to post-translational regulation.

PMID- 16442805
TI  - Gene expression profiling in frataxin deficient mice: microarray evidence for
      significant expression changes without detectable neurodegeneration.
AB  - Friedreich's ataxia (FRDA) is caused by reduction of frataxin levels to 5-35%. To
      better understand the biochemical sequelae of frataxin reduction, in absence of
      the confounding effects of neurodegeneration, we studied the gene expression
      profile of a mouse model expressing 25-36% of the normal frataxin levels, and not
      showing a detectable phenotype or neurodegenerative features. Despite having no
      overt phenotype, a clear microarray gene expression phenotype was observed. This
      phenotype followed the known regional susceptibility in this disease, most
      changes occurring in the spinal cord. Additionally, gene ontology analysis
      identified a clear mitochondrial component, consistent with previous findings. We
      were able to confirm a subset of changes in fibroblast cell lines from patients.
      The identification of a core set of genes changing early in the FRDA pathogenesis
      can be a useful tool in both clarifying the disease process and in evaluating new
      therapeutic strategies.

PMID- 16442807
TI  - Reversed remodelling in dilated cardiomyopathy by passive containment surgery is
      associated with decreased circulating levels of endothelin-1.
AB  - OBJECTIVE: To evaluate the influence on circulating levels of endothelin-1 and
      big endothelin-1 in relation to echocardiographic findings and functional
      assessment, by passive containment surgery in heart failure patients with dilated
      cardiomyopathy. METHODS: Thirteen patients with dilated cardiomyopathy subjected
      to cardiac surgery received the Acorn Cardiac Support Device. Patients with
      ischemic dilated cardiomyopathy (n=6) underwent coronary artery bypass surgery
      receiving one to three bypass grafts. In the idiopathic dilated cardiomyopathy
      group (n=7), mitral valve plasty was performed in five patients while two
      patients received the cardiac support device only. Circulating plasma levels of
      endothelin-1 and big endothelin-1 were measured in all patients before surgery
      and 12 months after surgery. Concomitantly New York Heart Association functional
      class and 6-min walk were evaluated and cardiac dimensions measured with
      echocardiography. RESULTS: Following surgery there was a significant decrease in
      circulating plasma levels of endothelin-1 (5.9+/-0.6 pM preoperatively vs 4.3+/
      0.3 pM postoperatively, P<0.05). New York Heart Association functional class
      improved (2.8+/-0.2 preoperatively vs 1.8+/-0.2 postoperatively, P<0.05). The 6
      min walk increased (384+/-24 m preoperatively vs 465+/-33 m postoperatively,
      P<0.05). There was also a decrease in left ventricular end diastolic diameter
      (69+/-2mm preoperatively vs 62+/-2mm postoperatively, P<0.05) and left
      ventricular end systolic diameter (60+/-2mm preoperatively vs 54+/-3mm
      postoperatively, P<0.05). Linear correlation revealed a relationship between
      decreased left ventricular end diastolic diameter and decreased endothelin-1
      levels (R=0.56; P<0.05). CONCLUSIONS: Following passive containment surgery using
      the Acorn Cardiac Support Device there is a decrease in circulating levels of
      endothelin-1 concomitant with a decrease in cardiac dimensions and function
      improvement.

PMID- 16442808
TI  - The effect of skin permeation enhancers on the formation of porphyrins in mouse
      skin during topical application of the methyl ester of 5-aminolevulinic acid.
AB  - The influence of skin permeation enhancers, such as dimethyl sulphoxide (DMSO)
      and 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), Labrafac CC, Labrafil,
      Labrasol and Transcutol in a concentration of 10% (wt./wt.) on the formation of
      porphyrins in normal mouse skin from topical application of creams with methyl 5
      aminolevulinate (MAL) was studied. The concentration of porphyrins in the mouse
      skin was determined by direct fluorescence measurements. The results show that
      studied permeation enhancers increase the formation of porphyrins, and therefore
      also the skin penetration 2% MAL whereas for 10% and 20% (wt./wt.) MAL
      concentrations only DMSO, HPE-101 and Labrafac CC increased the porphyrin
      formation. At all studied MAL concentrations DMSO gave the largest enhancing
      effect, similarly to that of HPE-101. This suggests that in 2-20% MAL creams HPE
      101 may be substituted by Labrafac CC to reduce skin irritation induced by HPE
      101 without impairing the porphyrin formation.

PMID- 16442809
TI  - Photo-dynamic biocidal action of methylene blue and hydrogen peroxide on the
      cyanobacterium Synechococcus leopoliensis under visible light irradiation.
AB  - Biofilm growth on stone surfaces is a significant contributing factor to stone
      biodeterioration. Current market based biocides are hazardous to the environment
      and to public health. We have investigated the photo-dynamic effect of methylene
      blue (MB) in the presence of hydrogen peroxide (H2O2) on the destruction of the
      cyanobacterium Synechococcus leopoliensis (S. leopoliensis) under irradiation
      with visible light. Data presented in this paper illustrate that illumination of
      S. leopoliensis in the presence of a photosensitiser (MB) and H2O2 results in the
      decomposition of both the cyanobacterium and the photosensitiser. The presence of
      MB and H2O2 affects the viability of the photosensitiser and the cyanobacterium
      with the fluorescence of both decreasing by 80% over the irradiation time
      investigated. The photo-dynamic effect was observed under aerobic and anaerobic
      conditions indicating that oxygen was not necessary for the process. This novel
      combination could be effective for the remediation of biofilm colonised stone
      surfaces.

PMID- 16442810
TI  - Unraveling the differential expression of the two isoforms of myelin-associated
      glycoprotein in a mouse expressing GFP-tagged S-MAG specifically regulated and
      targeted into the different myelin compartments.
AB  - The two myelin-associated glycoprotein (MAG) isoforms are cell adhesion molecules
      that differ only in their cytoplasmic domains, but their specific roles are not
      well understood. In this study, we present a transgenic mouse line that
      specifically expresses GFP-tagged S-MAG correctly regulated and targeted into the
      myelin sheath allowing the specific discrimination of L- and S-MAG on the
      subcellular level. Here, we describe the differential expression pattern and
      spatial distribution of L- and S-MAG during development as well as in the adult
      central and peripheral nervous system. In peripheral nerves, where S-MAG is the
      sole isoform, we observed S-MAG concentrated in different ring-like structures
      such as periaxonal and abaxonal rings, and discs spanning through the compact
      myelin sheath perpendicular to the axon. In summary, our data provide new insight
      in the subcellular distribution of the two isoforms fundamental for the
      understanding of their specific functions in myelin formation and maintenance.

PMID- 16442813
TI  - Awareness is relative: dissociation as the organisation of meaning.
AB  - This essay discusses how the organisation of mental material within the cognitive
      system can influence consciousness and awareness, and presents a theory of
      dissociation based on the premise that awareness is relative, contingent on the
      activated representation of the ongoing event being linked to the activated self
      representation. It allows four possible variations of integration: (i) non
      integrated experience--perceptions about an object/event are either not perceived
      or they remain at the sensory level: traditional dissociative states, amnesia,
      depersonalisation etc; (ii) variably integrated experience--activation of
      information of a specific valence about an object blocks activation of
      information of contrasting valence: splitting; (iii) alternatively integrated
      experience--experience is integrated into a specific, limited active self
      representation: fugue and multiple identity states; (iv) dis-integrated
      experience-the ongoing experience of innate drives and needs is no longer
      consistently activated in the core self-representation: repression and isolation.

PMID- 16442812
TI  - Mucosal immunisation: Successful approaches to targeting different tissues.

PMID- 16442811
TI  - Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal
      vaccine delivery systems.
AB  - Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend
      and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were
      investigated for their potential as a mucosal vaccine delivery system. The
      nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion
      solvent evaporation method, demonstrated release profiles which were dependent on
      the properties of the polymers. An in vitro experiment using Caco-2 cells showed
      significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA,
      the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by
      the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo
      studies following nasal administration. PCL nanoparticles induced DT serum
      specific IgG antibody responses significantly higher than PLGA. A significant
      positive correlation between hydrophobicity of the nanoparticles and the immune
      response was observed following intramuscular administration. The positive
      correlation between hydrophobicity of the nanoparticles and serum DT specific IgG
      antibody response was also observed after intranasal administration of the
      nanoparticles. The cytokine assays showed that the serum IgG antibody response
      induced is different according to the route of administration, indicated by the
      differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the
      highest IgG antibody response did not necessarily elicit the highest levels of
      the cytokines IL-6 and IFN-gamma.

PMID- 16442814
TI  - Being ourselves and knowing ourselves: an adverbial account of mental
      representations.
AB  - This paper takes an evolutionary approach to what we are, namely autopoietic
      systems with a first person perspective on our surroundings and ourselves. This
      in contrast with Thomas Metzinger's views in his Being No One. Though perception
      does involve internal processing and representations, it is argued that
      perception is direct. We track real features of the world, but fallibly, in a
      certain way. Moreover, it is claimed that mental representations are quite
      different from internal neural representations. They are best construed in an
      adverbial way. What we perceive, the object of perception, is the real world.
      Internal neural representations are the means by which we perceive the world. And
      mental representations are the way in which we experience the world, the
      adverbial content of perception. Finally, what goes for the world goes for
      ourselves as well: in self-consciousness we track real features of ourselves, but
      fallibly, in a certain way.

PMID- 16442815
TI  - Consciousness of the self (COS) and explicit knowledge.
AB  - Starting with distinction between explicit and implicit knowledge and the
      traditional philosophical distinction between COS (the consciousness of self) as
      an object and COS as a subject, we suggest a triple classification of COS
      experience into three modes, each corresponding to a different state of
      consciousness. When one acts automatically COS is totally embedded within the
      representation of the environment. When one monitors or attends to one's
      experience, the self is implied by an explicit representation of one's attitudes,
      consistent with Descartes' cogito insight 'I think therefore I am' (1641,1984).
      However, a reflexive thought, e.g., 'I know fact x,' requires an explicit
      representation of the self. This analysis highlights the existence of an
      intermediate mode of COS as a subject and suggests its possible connection to
      monitoring one's behavior.

PMID- 16442818
TI  - Off-label use of Angio-Seal vascular closure device for brachial artery puncture
      closure-deployment modification and initial results after transbrachial PTA.

PMID- 16442816
TI  - Magnetic resonance imaging of functional Schwann cell transplants labelled with
      magnetic microspheres.
AB  - There is increasing interest in the use of magnetic resonance imaging (MRI)
      methods for tracking the fate of labelled cells in vivo post-implantation. The
      majority of studies have employed cell labels based on nanometer-sized ultrasmall
      dextran-coated iron oxide particles (USPIO), which are detected through signal
      hypointensity in T2-weighted images. Although sensitive to MR detection, these
      labels can be difficult to distinguish from other sources of signal loss in vivo
      and can be diluted by cell division. Recently, a micron-sized cell label has been
      described that is much more sensitive to MR detection and which allows detection
      of single labels in vivo. We show here that glial cells readily take up this
      label in culture and that the labelled Schwann cells can be detected in vivo by
      MRI following their implantation into a demyelinated lesion in the rat spinal
      cord. Signal loss due to the label is sufficiently great that the labelled cells
      can easily be distinguished from surrounding haemorrhage at the lesion site.
      Subsequent histological analysis of the lesion area showed that the transplanted
      cells were remyelinating the demyelinated axons, demonstrating that the labelled
      cells retained their biological function and that the majority of the label had
      remained within the transplanted cells.

PMID- 16442817
TI  - Statistical parametric mapping of brain morphology: sensitivity is dramatically
      increased by using brain-extracted images as inputs.
AB  - A major attraction of voxel-based morphometry (VBM) is that it allows researchers
      to explore large datasets with minimal human intervention. However, the validity
      and sensitivity of the Statistical Parametric Mapping (SPM2) approach to VBM are
      the subject of considerable debate. We visually inspected the SPM2 gray matter
      segmentations for 101 research participants and found a gross inclusion of non
      brain tissue surrounding the entire brain as gray matter in five subjects and
      focal areas bordering the brain in which non-brain tissue was classified as gray
      matter in many other subjects. We also found many areas in which the cortical
      gray matter was incorrectly excluded from the segmentation of the brain. The
      major source of these errors was the misregistration of individual brain images
      with the reference T1-weighted brain template. These errors could be eliminated
      if SPM2 operated on images from which non-brain tissues (scalp, skull, and
      meninges) are removed (brain-extracted images). We developed a modified SPM2
      processing pipeline that used brain-extracted images as inputs to test this
      hypothesis. We describe the modifications to the SPM2 pipeline that allow
      analysis of brain-extracted inputs. Using brain-extracted inputs eliminated the
      non-brain matter inclusions and the cortical gray matter exclusions noted above,
      reducing the residual mean square errors (RMSEs, the error term of the SPM2
      statistical analyses) by over 30%. We show how this reduction in the RMSEs
      profoundly affects power analyses. SPM2 analyses of brain-extracted images may
      require sample sizes only half as great as analyses of non-brain-extracted
      images.

PMID- 16442819
TI  - Effects of 1400W, a potent selective inducible NOS inhibitor, on histamine- and
      leukotriene D4-induced relaxation of isolated guinea pig nasal mucosa.
AB  - To clarify the role of inducible nitric oxide synthase (iNOS) in the relaxation
      of nasal vasculature, the effects of a potent selective iNOS inhibitor, N-[(3
      aminomethyl)benzyl]acetamidine (1400W), on histamine- and leukotriene D4 (LTD4)
      induced relaxations of isolated nasal septal mucosae were examined in naive
      guinea pigs. In addition to eNOS and nNOS, Western blots demonstrated a distinct
      expression of iNOS in nasal mucosal tissues of naive guinea pigs. In isolated
      nasal septal mucosae precontracted with norepinephrine (3 x 10(-5)M), both
      histamine (10(-7)-10(-3)M) and LTD4 (10(-10)-10(-7)M) exhibited relaxations,
      which were inhibited by a NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(
      4)M). The inhibitory effect of L-NMMA was reversed by L-arginine (10(-3)M),
      indicating that the relaxations induced by histamine and LTD4 are mediated by NO.
      Furthermore, both the histamine- and LTD4-induced relaxations were also
      significantly attenuated by 1400W (10(-5)M). These findings suggest an
      involvement of NO generated by iNOS in agonist-induced relaxation of nasal
      mucosal vasculature in naive guinea pigs.

PMID- 16442820
TI  - Cardiac expression and distribution of nitric oxide synthases in the ventricle of
      the cold-adapted Antarctic teleosts, the hemoglobinless Chionodraco hamatus and
      the red-blooded Trematomus bernacchii.
AB  - The presence of nitric oxide synthase (NOS) was investigated in the ventricle of
      two Antarctic teleosts, the hemoglobinless icefish Chionodraco hamatus and its
      red-blooded counterpart, Trematomus bernacchii. Under unstimulated conditions, in
      both teleosts, NADPH-diaphorase localised NOS activity in the endocardial
      endothelial cells (EEc) and in the myocardiocytes. Application of anti-mammalian
      endothelial and inducible NOS (eNOS and iNOS, respectively) primary antibodies
      for immunofluorescence revealed a comparable tissue-specific basal expression of
      the two isoforms in the two species. eNOS strongly localised at the level of the
      EEc and, in T. bernacchii, of the vascular endothelium (VE). The enzyme is also
      localised, albeit to less extent, within the myocardiocytes, and in the
      epicardium. In contrast, iNOS immunostaining only labels the cytoplasm of the
      ventricular myocytes. Western blotting analysis identified two peptides with
      molecular masses of about 135 and 130kDa, similar to those of the mammalian eNOS
      and iNOS. To verify whether this NOS system is susceptible to septic stimulation,
      C. hamatus and T. bernacchii were exposed to bacterial lipopolysaccharides (LPS).
      The treatment did not modify the distribution pattern of the two isoenzymes while
      it increased the amount of NADPH-diaphorase-dependent reaction product and the
      expression of both eNOS and iNOS. These results indicate a high phylogenetic
      conservation of the intracardiac NOS system, emphasizing its importance in the
      control of the vertebrate heart and its relevance as a general mechanism of
      defense against pathogens.

PMID- 16442821
TI  - Original investigation of right-to-left shunting patent ductus arteriosus in an
      Irish setter puppy.
AB  - A six-month-old, entire female, Irish setter was presented with a two-month
      history of progressive hindlimb weakness and collapse on exercise. Thoracic
      auscultation revealed a soft systolic murmur and a split second heart sound.
      Differential cyanosis and polycythaemia were not observed. Right-to-left shunting
      patent ductus arteriosus (r-PDA) was confirmed on contrast echocardiography
      ("bubble study") and selective right ventricular angiography. Comparison of blood
      gases from the metatarsal and auricular artery confirmed the presence of
      differential hypoxia. This technique is not known to have been described
      previously in the diagnostic investigation of r-PDA in dogs.

PMID- 16442822
TI  - Long-term IGF-I treatment of children with Laron syndrome increases adiposity.
AB  - Laron syndrome (LS) is an autosomal recessive disease caused by deletions or
      mutations in the GH receptor gene leading to an inability of insulin-like growth
      factor I (IGF-I) generation. Among the major resulting body changes are dwarfism
      and obesity. The only effective treatment is daily administration of biosynthetic
      IGF-I. Body composition determination by DEXA (dual energy X-ray absorptiometry)
      of three girls with LS treated by IGF-I for 1, 3 and 11 1/2 years, respectively,
      revealed that concomitantly with the increase in growth there was a significant
      increase in body adipose tissue to double or triple the normal values. Due to the
      underdevelopment of the muscular and skeletal systems body mass index (BMI) did
      not accurately reflect the degree of obesity. In conclusion, IGF-I similar to
      insulin, exerts an adipogenic effect.

PMID- 16442823
TI  - Effects of a single dose of an intranasal feline herpesvirus 1, calicivirus, and
      panleukopenia vaccine on clinical signs and virus shedding after challenge with
      virulent feline herpesvirus 1.
AB  - The objective of this study was to determine whether intranasal administration of
      a commercially available FVRCP vaccine to kittens lessened clinical signs and
      feline herpesvirus 1 (FHV-1) viral shedding when compared to unvaccinated control
      kittens after FHV-1 challenge. Three groups of 10 unvaccinated kittens were
      administered one dose of vaccine 6 days (group 1), 4 days (group 2), or 2 days
      (group 3) before challenge, respectively. One group was maintained as
      unvaccinated controls (group 4). FHV-1 challenge was then induced and the kittens
      were observed for 14 days. When the grouped vaccinated kitten results (groups 1
      3) were compared to group 4 results, clinical scores following challenge were
      significantly lower (P<0.05) and significantly lower body temperatures (P<0.05)
      were detected on days 0, 5 and 9 post-challenge. When evaluated by individual
      group, group 1 and group 2 kittens had significantly lower clinical scores
      (P<0.05) than group 4 kittens post-challenge. In addition, FHV-1 shedding was
      lower in group 1 kittens when compared to group 4 kittens on day 6 after
      challenge (P<0.05). Administration of this vaccine within several days prior to
      exposure lessened clinical signs of disease and FHV-1 shedding compared to
      unvaccinated kittens.

PMID- 16442825
TI  - A questionnaire-based study of gestation, parturition and neonatal mortality in
      pedigree breeding cats in the UK.
AB  - This study was based on a convenience-sampling questionnaire study of pedigree
      cat breeding in the UK. Data were collated for the births of 1,056 litters from
      14 different pedigree breeds and 942 different households. Significant
      relationships between various outcomes and relevant predictors were assessed by
      multiple linear regression or logistic regression as appropriate. The overall
      mean gestation length of 65.1 days varied significantly between the breeds
      (P<0.0001), and larger litter sizes were associated with shorter gestation
      lengths (P=0.04). The mean litter size of 4.6 kittens also varied significantly
      according to breed (P<0.0001). The weight of kittens born alive (overall mean
      93.5 g) increased with longer gestation lengths (P=0.0003), decreased with larger
      litter sizes (P<0.0001) and varied between the breeds (P<0.0001). A total of 8.0%
      of pregnancies resulted in a caesarean section, with a higher risk associated
      with smaller litter sizes (P=0.002). Although the frequency of caesarean sections
      varied from 0 to 18.5% between individual breeds, breed itself was not shown to
      have a significant independent effect on this likelihood. A mean of 7.2% of all
      the kittens were stillborn, which varied according to breed (P=0.0003), and the
      risk of a stillborn kitten increased with litter size (P=0.0001), and with the
      presence of congenital defects in the litter (P=0.0002). The mean kitten
      mortality between birth and 8 weeks of age was 9.1%, and the majority of these
      occurred in the first week of life. Parturition intervals varied widely. The
      duration of first stage of labour was less than 2h in 82.9% of cats. The interval
      between the birth of the first and last kitten was less than 6h in 85.7%, but
      more than 48 h in three cats. A maximum of 48 h was recorded between the births
      of individual kittens in unassisted deliveries.

PMID- 16442824
TI  - A retrospective study of (90)Strontium plesiotherapy for feline squamous cell
      carcinoma of the nasal planum.
AB  - The responses of 15 cats with histologically (n=14) or cytologically (n=1)
      confirmed nasal squamous cell carcinoma treated with (90)Strontium plesiotherapy
      were reviewed retrospectively. Cats were treated such that a total dose of 50Gy
      was delivered at a depth of 2mm, administered in five fractions over a 10-day
      period. Of the cats, 11 were stage T(2), three were T(is) and one had only a
      cytological diagnosis precluding staging. Eleven of the cats achieved complete
      response (no visible lesion after 6-8 weeks) following the first cycle of
      therapy, and two cats with partial response achieved complete response with a
      second cycle of therapy. The remaining two cats achieved partial response
      following therapy, but further intervention was declined. Euthanasia was
      performed in these two cats because of progressive disease after 81 and 142 days.
      Of the 85% of cats that achieved a complete response, there was no recurrence of
      disease during a follow-up period of 134-2,043 days (median 652 days). In
      addition to prolonged disease-free survivals, (90)Strontium therapy produced
      excellent cosmetic results from the owners' perspective. These results
      demonstrate that superficial squamous cell carcinoma of the feline nasal planum
      responds excellently to (90)Strontium plesiotherapy, and this form of therapy may
      offer advantages over other alternatives currently available.

PMID- 16442826
TI  - Dorso-medial ante-brachiocarpal luxation with radio-ulna luxation in a domestic
      shorthair.
AB  - An 8-year-old domestic shorthair was admitted with non-weight bearing left
      forelimb lameness. Examination and radiographs revealed dorso-medial ante
      brachiocarpal luxation with palmar luxation of the distal radio-ulnar joint.
      Primary repair was performed and stabilised using an arthrodesis wire and type Ia
      Kirschner-Ehmer (K-E) external skeletal fixator (ESF). The cat regained excellent
      pain-free limb function by 14 weeks with only minor reduction in range of
      movement. This is the first case report of a cat with distal radio-ulnar joint
      luxation associated with ante-brachiocarpal luxation. Primary repair of carpal
      luxation in the cat should be considered before arthrodesis.

PMID- 16442827
TI  - [Soft tissue sarcomas: update on molecular data].
AB  - Soft tissue sarcomas are rare and may be a source of problems for diagnosis and
      treatment. Four types of genetic disorders can be distinguished: translocations,
      gene amplifications, mutations and complex genetic imbalances. Detection of these
      disorders may help in diagnosis and in determining prognosis. Detection of
      specific translocation is recommended in synovial sarcoma, alveolar
      rhabdomyosarcoma or PNET diagnosis because of therapeutic consequences; in case
      of rarer histologic type (low grade fibromyxoid sarcoma, clear cell sarcoma,
      infantile fibrosarcoma...), it may confirm the diagnosis. In some cases, some
      translocations have a prognostic value (alveolar rhabdomyosarcoma) whereas it is
      discussed in others (synovial sarcoma). The techniques used to detect these
      translocations are very sensitive so it may be used to detect microscopical
      metastasis (bone marrow metastasis of alveolar rhabdomyosarcoma for example).
      Detection of MDM2 and CDK4 genes amplifications (FISH or quantitative PCR) may be
      sometimes useful in well differentiated and dedifferentiated liposarcomas
      diagnosis. Mutation detection of KIT or PDGFRA may help in GIST diagnosis and
      type of mutation is predictive of response to treatment. Study of complex genomic
      imbalances in sarcomas is not used in routine practice but remains useful in
      research.

PMID- 16442828
TI  - [Limb and retroperitoneal sarcomas: progress with an optimal multidisciplinary
      management].

PMID- 16442829
TI  - Influence of recording instrumentation on the stimulus artifact tail in the
      surface acquisition of somatosensory evoked potentials.
AB  - Surface recorded somatosensory evoked potentials (SEPs) are neural signals
      elicited by an external stimulus. In the case of electrically induced SEPs, the
      artifact generated by the stimulation process can severely distort the signal.
      The artifact is characterized by a large impulse followed by a slowly decaying
      tail. In some cases, the artifact tail often lasts well into the initiation of
      the SEP making the determination of absolute latency very difficult. While the
      literature often states that the recording instrumentation plays a part in the
      generation of this artifact tail, no firm evidence has ever been presented. In
      this work, comparisons are made between three instrumentation systems (BJT, JFET
      and CMOS) with differing input impedances in an attempt to quantify the effects
      on the artifact tail. The conclusions from this investigation show that there is
      no significant interaction between the input impedance of the recording
      instrumentation and the duration of the artifact tail. Each amplifier type
      produced results with no significant statistical differences. It was also found
      that while stimulation amplitude has a weak effect on the artifact tail, the
      greatest contribution to variation has an inter-subject origin. Consequently, it
      is concluded that the time constant of the artifact tail must originate from
      other sources that are subject dependent.

PMID- 16442830
TI  - Serial cholinesterase estimation in carbamate poisoning.
AB  - Poisoning is one of the most important causes of morbidity and mortality in
      developing countries like India. Anticholinesterase compounds like
      organophosphates (OP) and carbamates account for the majority of these poisoning
      cases because of their easy availability and agricultural use. Carbamates are as
      popular as OPs as insecticides that often go undiagnosed. A fatal case of
      carbofuran poisoning is presented where serial cholinesterase estimation played a
      major role in the diagnosis of the same. The pertinent medical literature on
      carbofuran poisoning is reviewed. The establishment of poison information center
      in each state is needed for proper diagnosis and management of poisoning cases.

PMID- 16442831
TI  - Retained intra cranial blade - medicolegal perspectives.
AB  - A fatal case of a homicidal penetrating head injury by retained blade of knife is
      reported. The blade of knife penetrated the skull bone after breaking from a
      knife handle and remained lodged in the intracranial cavity for 5 days resulting
      in death from intracranial bleeding and brain oedema. The need of proper and
      complete examination of the head injury and its medico-legal importance is
      emphasized.

PMID- 16442832
TI  - Investigation into the suitability of a portable psychometric device to be used
      in the field: an illicit drugs field investigation.
AB  - RATIONALE: Driving performance is easily disrupted as a direct consequence of the
      use of alcohol, licit and illicit drugs. The use of such drugs has a high degree
      of correlation with increased accident risk. Europe wide research projects into
      drugged driving have called for the development of a portable objective device
      capable of screening those impaired through drug use which can be used at the
      roadside. OBJECTIVE: This study investigated the cognitive and psychomotor
      performance of a cohort of polydrug drug users in field conditions. Volunteers
      completed a psychometric test battery on a hand held device in music festival
      conditions. The test battery comprised a critical tracking task (CTT) and a
      sustained attention to response task (SART). Volunteers also took a
      breathanalyser and provided a saliva sample for a DOA screen. RESULTS: On the CTT
      significance was observed for tracking error following response to a peripheral
      stimulus in the high alcohol (>80 mg/100 ml) illicit drug group (p=0.0090) and
      approached significance for the low alcohol (<80 mg/100 ml) illicit drug group
      (p=0.088). For the SART, incorrect presses to the target stimulus was impaired
      for volunteers in both the low (<80 mg/100 ml) alcohol illicit drug group
      (p=0.0080) and the high alcohol (>80 mg/100 ml) illicit drug group (p=0.0415).
      Discrimination analysis demonstrated that the impairment device was able to
      discriminate between those individuals who had consumed neither alcohol nor drugs
      (94.12%), those in the low alcohol drug group (46.67%) and those in the high
      alcohol drug group (60.00%). CONCLUSION: It is possible to derive an impairment
      ratio. Further research will demonstrate whether this device could significantly
      contribute to drug driving detection and road traffic safety.

PMID- 16442833
TI  - Haemorrhoids leading to post-mortem bleeding artefact.
AB  - We present a case where a 54-year-old man suffering from haemorrhoids, committed
      suicide by hanging. Gravitational forces due to the upright position of the body
      facilitated post-mortem per-rectal bleeding from the ulcerated haemorrhoids. The
      bleeding stained his under garment and wrap around cloth. Frank blood was also
      seen on the floor beneath the hanging body. The blood at the crime scene was
      wrongly interpreted by the investigating police as that due to self-inflicted
      injury or possibly case of homicide followed by post-mortem suspension of the
      body. Observation of the crime scene by forensic medicine experts and subsequent
      autopsy findings revealed that the bleeding was from the haemorrhoids. This case
      is reported for its rarity, for the awareness of the possible post-mortem
      haemorrhoidal bleeding artefact, to explain the circumstances of such a
      possibility, and to emphasize the importance of involving forensic medicine
      experts as a part of the crime scene investigation team.

PMID- 16442834
TI  - Oxidative stress in diabetes: a mechanistic overview of its effects on
      atherogenesis and myocardial dysfunction.
AB  - Diabetes is a major risk factor for atherosclerosis. Atherogenesis involves
      endothelial dysfunction, activation and injury, inflammation, and smooth muscle
      cell migration and proliferation. Platelet activation in the narrowed arteries is
      the most proximate event in the culmination of an acute event such as acute
      myocardial infraction and stroke. Hyperglycemia is associated with all these
      adverse events in the process of genesis of atherosclerosis. The effect of
      diabetes (hyperglycemia) is mediated in large part by the state of enhanced
      oxidative stress, which is not counter-balanced by endogenous antioxidants. This
      paper reviews the ignition of oxidative stress in diabetes and the mediation of
      events leading to atherogenesis.

PMID- 16442835
TI  - The Akt inhibitor KP372-1 inhibits proliferation and induces apoptosis and
      anoikis in squamous cell carcinoma of the head and neck.
AB  - Therapies that target signaling pathways critical to the pathogenesis and
      progression of squamous cell carcinoma of the head and neck (HNSCC) are needed.
      One such target, phosphatidylinositol 3-kinase, and its downstream target
      serine/threonine kinase, Akt, are up-regulated in HNSCC. Targeted therapy could
      consist of inhibitors of these kinases or, alternatively, of inhibitors of the
      pathways that they regulate. To explore the effect of Akt inhibition on the
      growth and survival of HNSCC tumors, we evaluated the effect of a novel Akt
      inhibitor, KP372-1, on the growth, survival, and sensitivity to anoikis of HNSCC
      cell lines in culture. Using Western blotting of head and neck cancer cell lines
      and squamous mucosa and carcinoma specimens, we found that Akt was highly
      phosphorylated in head and neck cancer cell lines and human head and neck
      squamous carcinoma specimens. Treatment of HNSCC cell lines with KP372-1 blocked
      the activation of Akt, inhibited head and neck cancer cell proliferation, and
      induced apoptosis and anoikis in several HNSCC cell lines. Furthermore, KP372-1
      decreased the phosphorylation of the S6 ribosomal (Ser240/244) protein, which is
      a downstream target of Akt. Taken together, these findings indicate that KP372-1
      may be a useful therapeutic agent for HNSCC and should be further evaluated in
      preclinical models of HNSCC.

PMID- 16442836
TI  - In vivo evaluation of induction of abnormal sperm morphology in mice by an
      unsaturated aldehyde crotonaldehyde.
AB  - Crotonaldehyde, a highly reactive unsaturated aldehyde is used for the
      manufacture of sorbic acid, synthesis of butyl alcohol, butylaldehyde,
      quinaldine, thiophenes, pyridines, dyes, pesticides, pharmaceuticals, rubber
      antioxidants, chemical warfare agents, etc. and also occurs naturally in meat,
      fish, in many fruits and vegetables, bread, cheese, milk, beer, wine and liquors.
      Human exposure to crotonaldehyde occurs from both man-made and natural sources.
      No human data was located describing carcinogenicity associated with
      crotonaldehyde exposure. In the present study we have evaluated whether or not
      exposure to crotonaldehyde results in a significant increase in the frequency of
      abnormal sperm heads in male Swiss albino mice. Adult male mice were treated with
      8, 16 and 32 microl/kg b.w. of crotonaldehyde as a single intraperitoneal
      injection. The animals were killed 1, 3 and 5 weeks after treatment. Five animals
      were sacrificed per dose and time tested. Crotonaldehyde induced dose related
      increase in the percentage of abnormal sperm heads. Statistically significant
      increase in percentage of abnormal sperm heads was recoded at 16 and 32 microl/kg
      b.w. after 1 and 3 weeks of treatment and only at 32 microl/kg b.w. after 5 weeks
      of treatment.

PMID- 16442837
TI  - Comparison of genetic damage in Brazilian footwear-workers exposed to solvent- or
      water-based adhesive.

PMID- 16442838
TI  - Experimental preparation and UV/IR spectroscopic characterization of 1,3
      dibutanal-1,2,4,5-tetroxane.
AB  - We report the experimental preparation of the 1,3-butanal-1,2,4,5-tetroxane by
      oxidation of glutataldehyde with oxygen peroxide in presence of concentrated
      sulfuric acid, following the Bayer and Viller method modified by Jorge et al. The
      UV and IR spectra are studied from the experimental and theoretical standpoint. A
      rather complete vibrational assignment was performed and the nature of the
      electronic transitions was discussed in detail.

PMID- 16442839
TI  - Temperature and pressure dependence of the Raman frequency shifts near the
      melting point in ice I.
AB  - This study examines the validity of the spectroscopic modification of the Pippard
      relations for the hexagonal ice (ice I) close to the melting point. A linear
      variation of the specific heat CP with the frequency shifts EQUATION: SEE TEXT is
      obtained for ice I. This linearity is also obtained between thermal expansivity
      alphaP and the frequency shifts EQUATION: SEE TEXT close to the melting point in
      this crystal.

PMID- 16442840
TI  - Luminescense properties of new complexes of Eu(III) and Tb(III) with heterotopic
      ligands.
AB  - As a result of coordination between ligands L and L' and europium(III) and
      terbium(III) ions, the new architectures were formed. The formulae of the
      complexes have been assigned on the basis of the spectroscopic data in solution
      and microanalyses. The europium complexes show excellent luminescence properties
      with high quantum yield (1b-Eu(3)L(2)) and effective intramolecular energy
      transfer from the ligand to the Eu(III) ions.

PMID- 16442841
TI  - Vibrational spectra and molecular structure of chiral and racemic 4-phenyl-1,3
      oxazolidin-2-one by density functional theory and ab initio Hartree-Fock
      calculations.
AB  - The vibrational frequencies and molecular geometry of (R)- and (rac)-4-phenly-1,3
      oxazolidin-2-one (4-POO) in the ground state have been calculated using the
      Hartree-Fock and density functional method (B3LYP) with 6-31G(d) basis set. The
      optimized geometric bond lengths are described better by HF while bond angles are
      reproduced more accurately by DFT (B3LYP). Comparison of the observed fundamental
      vibrational frequencies of (R)-POO and (rac)-4-POO and calculated results by
      density functional B3LYP and Hartree-Fock methods indicate that B3LYP is superior
      to the scaled Hartree-Fock approach for molecular vibrational problems.

PMID- 16442842
TI  - NMR spectra of free-base porphine, porphyrazine, phthalocyanine and
      naphthalocyanine as well as their metal complexes: density functional
      calculations.
AB  - Nuclear magnetic shielding tensors of porphine have been calculated at density
      functional B3LYP and PBE level using the gauge independent atomic orbital (GIAO)
      method. The geometries used were optimized using the 6-31G(d) basis set and the
      NMR calculations were performed using 6-31G(d) and 6-311G(d,p) basis sets,
      respectively. The calculated NMR shielding tensors and chemical shifts of
      porphine are compared with previous calculations as well as experimental data and
      satisfying results are obtained. Further NMR calculations are extended to metal
      free and metallo-porphyrazine, -phthalocyanine, and -naphthalocyanine for the
      first time and the results are compared with experimental data available. The
      chemical shifts of the atoms in these compounds are assigned according to the
      experimental data available.

PMID- 16442843
TI  - Triacylglycerol accumulation is not primarily affected in myotubes established
      from type 2 diabetic subjects.
AB  - In the present study, we investigated triacylglycerol (TAG) accumulation, glucose
      and fatty acid (FA) uptake, and glycogen synthesis (GS) in human myotubes from
      healthy, lean, and obese subjects with and without type 2 diabetes (T2D), exposed
      to increasing palmitate (PA) and oleate (OA) concentrations with/without high
      glucose and/or high insulin concentrations for 4 days. We showed that these
      myotubes expressed an increased TAG accumulation (P<0.001) without differences
      between groups. Chronically high insulin, but not high glucose concentrations,
      increases TAG accumulation by 25% (P<0.001). Inhibition of oxidative
      phosphorylation by antimycin A and oligomyin was followed by a reduced lipid
      oxidation (P<0.05) and increased TAG accumulation (P<0.05), but only in the
      presence of FAs. Both chronic PA and OA exposure reduced the insulin-mediated PA
      and OA uptake (fold change) (P<0.001), but could not induce insulin resistance at
      the level of glucose uptake, whereas high insulin concentrations induced insulin
      resistance (P<0.001). Chronic, high PA, but not OA, induced insulin resistance at
      the GS level in control subjects (P<0.05). The TAG content correlated negatively
      with insulin-stimulated FA uptake (P<0.001), but did not correlate with insulin
      stimulated glucose uptake for PA or OA (P>0.05). These results indicate that (1)
      TAG accumulation is not primarily affected in skeletal muscle tissue of obese and
      T2D; (2) induced inhibition of oxidative phosphorylation is followed by TAG
      accumulation; (3) increasing FA and insulin availability, and reduced oxidative
      phosphorylation, and to a lesser extent glucose, are determinants for differences
      in intramyocellular TAG accumulation; (4) quantitative TAG content may not be the
      best marker for insulin resistance. Thus, increased TAG content in skeletal
      muscle of obese and T2D subjects is adaptive.

PMID- 16442844
TI  - Levosimendan therapy in decompensated chronic heart failure: favourable
      haemodynamic and neurohormonal effects but for how long?

PMID- 16442845
TI  - The role of sexual satisfaction, age, and cardiac risk factors in the reduction
      of post-MI anxiety.
AB  - BACKGROUND: Anxiety is common after myocardial infarction (MI); however, little
      is known about the role of sexual satisfaction and return to sexual activity on
      anxiety post-MI. AIM: To examine the role of sexual satisfaction in reducing
      anxiety post-MI. METHODS: Patients with acute myocardial infarction (MI)
      recruited from one U.S. medical center completed questionnaires at baseline while
      hospitalized and at 1, 3, and 5 months post-MI. This analysis includes 64
      patients compared on low or high anxiety at 5 months post-MI using sexual
      satisfaction and selected demographic and clinical variables in the analysis.
      RESULTS: Patients with high anxiety scores reported lower sexual satisfaction (p
      < .001) and a higher percentage of coronary risk factors (p < .01). The OLS
      regression model provided similar results with an adjusted R-square of .422,
      accounting for approximately 42% of anxiety (p < .001). Sexual satisfaction
      accounted for the most variance in the model, showing an inverse relationship
      between sexual satisfaction and anxiety. An inverse relationship also existed
      between age and anxiety. CONCLUSIONS: Anxiety is common after MI, and decreased
      sexual satisfaction appears to contribute to heightened anxiety. Attention to
      sexual concerns of MI patients before and after hospital discharge may improve
      psychosocial outcomes.

PMID- 16442846
TI  - Binding capacity of in vitro deglycosylated IgA1 to human mesangial cells.
AB  - IgA nephropathy (IgAN) is the most common glomerular disease and it is
      characterized by deposition of IgA1 molecules in mesangium. Recent studies had
      demonstrated that serum and mesangial IgA1 in IgAN were deglycosylated and IgA1
      could bind to human mesangial cells (HMC) through a novel receptor. The aim of
      the current study is to investigate and compare the binding capacities of
      different in vitro deglycosylated IgA1 on human mesangial cells. Serum IgA1 was
      purified by jacalin affinity chromatography and then was desialylated (DesIgA1)
      and/or degalactosylated (Des/DeGalIgA1) with neuraminidase and/or beta
      galactosidase. The efficacy of deglycosylations was assessed by Peanut agglutinin
      (PNA) and Vicia villosa (VV) lectin. The sizes of normal IgA1 and deglycosylated
      IgA1 were determined by Sephacryl S-300 chromatography and binding capacities to
      primary HMC were evaluated by radioligand binding assays. Normal IgA1 and
      deglycosylated IgA1 could bind to HMC in a dose-dependent, saturable manner. The
      maximal binding capacities and binding sites/cell of DesIgA1 and Des/DeGalIgA
      were significantly higher than that of normal IgA1. However, more aggregated IgA1
      was found in DesIgA1 and Des/DeGalIgA1. Scatchard analysis revealed a similar Kd
      of normal IgA1 and deglycosylated IgA1. The current study suggested that the
      binding capacities of DesIgA1 and Des/DeGalIgA1 to HMC were significantly higher
      than that of normal IgA1, which at least in part was due to more macromolecular
      IgA1 in deglycoslated IgA1. However, there were no significant differences in the
      affinities of normal IgA1, DesIgA1 and Des/DeGalIgA1 with HMC. Deglycosylated
      IgA1 might play an important role in pathogenesis of IgAN.

PMID- 16442849
TI  - Graph theoretic modeling of large-scale semantic networks.
AB  - During the past several years, social network analysis methods have been used to
      model many complex real-world phenomena, including social networks,
      transportation networks, and the Internet. Graph theoretic methods, based on an
      elegant representation of entities and relationships, have been used in
      computational biology to study biological networks; however they have not yet
      been adopted widely by the greater informatics community. The graphs produced are
      generally large, sparse, and complex, and share common global topological
      properties. In this review of research (1998-2005) on large-scale semantic
      networks, we used a tailored search strategy to identify articles involving both
      a graph theoretic perspective and semantic information. Thirty-one relevant
      articles were retrieved. The majority (28, 90.3%) involved an investigation of a
      real-world network. These included corpora, thesauri, dictionaries, large
      computer programs, biological neuronal networks, word association networks, and
      files on the Internet. Twenty-two of the 28 (78.6%) involved a graph comprised of
      words or phrases. Fifteen of the 28 (53.6%) mentioned evidence of small-world
      characteristics in the network investigated. Eleven (39.3%) reported a scale-free
      topology, which tends to have a similar appearance when examined at varying
      scales. The results of this review indicate that networks generated from natural
      language have topological properties common to other natural phenomena. It has
      not yet been determined whether artificial human-curated terminology systems in
      biomedicine share these properties. Large network analysis methods have potential
      application in a variety of areas of informatics, such as in development of
      controlled vocabularies and for characterizing a given domain.

PMID- 16442847
TI  - rAAV2 traffics through both the late and the recycling endosomes in a dose
      dependent fashion.
AB  - Inefficient trafficking of recombinant adeno-associated virus type-2 (rAAV2) to
      the nucleus is a major barrier for transduction. Using imaging and subcellular
      fractionation techniques, we evaluated the extent of rAAV2 movement through the
      late (Rab7) and recycling (Rab11) endosomes. Following rAAV2 infection of HeLa
      cells, immunoisolation of HA-Rab7- or HA-Rab11-tagged endosomes and intracellular
      colocalization of Cy3-labeled rAAV2 with EGFP-Rab7 or EGFP-Rab11 markers
      demonstrated dose-dependent trafficking of rAAV2 through the recycling and late
      endosomal compartments. At low multiplicities of infection (m.o.i. 100
      genomes/cell), rAAV2 predominantly trafficked to the Rab7 compartment. In
      contrast, rAAV2 predominantly trafficked to the recycling endosome at 100-fold
      higher m.o.i. siRNA studies inhibiting either Rab7 or Rab11 demonstrated that
      reducing Rab11 protein levels more significantly inhibited rAAV2 transduction on
      a per genome basis compared to inhibition of Rab7. Dose-response curves,
      comparing the m.o.i. of AV2Luc infection to relative transduction, also supported
      the hypothesis that viral movement through the Rab11 compartment at high m.o.i.
      is more competent for transgene expression ( approximately 100-fold) than virus
      that moves through the Rab7 compartment at low m.o.i. These findings suggest that
      strategies to shunt viral movement from the late to the recycling endosome may be
      effective at increasing viral transduction for gene therapy.

PMID- 16442848
TI  - Long-term doxycycline-regulated transgene expression in the retina of nonhuman
      primates following subretinal injection of recombinant AAV vectors.
AB  - Adeno-associated viral gene therapy has shown promise for the treatment of
      inherited and acquired retinal disorders. In most applications, regulation of
      expression is a critical concern for both safety and efficacy. The purpose of our
      study was to evaluate the ability of the tetracycline-regulatable system to
      establish long-term transgene regulation in the retina of nonhuman primates.
      Three rAAV vectors expressing the tetracycline-dependent transactivator (rtTA)
      under the control of either the ubiquitous CAG promoter or the specific RPE65
      promoter (AAV2/5.CAG.TetOn.epo, AAV2/4.CAG.TetOn.epo, and AAV2/4.RPE65.TetOn.epo)
      were generated and administered subretinally to seven macaques. We demonstrated
      that repeated inductions of transgene expression in the nonhuman primate retina
      can be achieved using a Tet-inducible system via rAAV vector administration over
      a long period (2.5 years). Maximum erythropoietin (EPO) secretion in the anterior
      chamber depends upon the rAAV serotype and the nature of the promoter driving
      rtTA expression. We observed that the EPO isoforms produced in the retina differ
      from one another based on the transduced cell type of origin within the retina
      and also differ from both the physiological EPO isoforms and the isoforms
      produced by AAV-transduced skeletal muscle.

PMID- 16442850
TI  - Biomedical ontologies: what part-of is and isn't.
AB  - Mereological relations such as part-of and its inverse has-part are fundamental
      to the description of the structure of living organisms. Whereas classical
      mereology focuses on individual entities, mereological relations in biomedical
      ontologies are generally asserted between classes of individuals. In general,
      this practice leaves some basic issues unanswered: type constraints of
      mereological relations, e.g., concerning artifacts and biological entities, the
      relation between parthood and time, inferred parts and wholes as well as a
      delimitation of parthood against spatial inclusion. Furthermore, mereological
      relations can be asserted not only between physical objects but also between
      biological processes and medical procedures. We analyze these ambiguities and
      make suggestions for a standardization of mereological relations in biomedical
      ontologies.

PMID- 16442851
TI  - Improving the classification of multiple disorders with problem decomposition.
AB  - Differential diagnosis of multiple disorders is a challenging problem in clinical
      medicine. According to the divide-and-conquer principle, this problem can be
      handled more effectively through decomposing it into a number of simpler sub
      problems, each solved separately. We demonstrate the advantages of this approach
      using abductive network classifiers on the 6-class standard dermatology dataset.
      Three problem decomposition scenarios are investigated, including class
      decomposition and two hierarchical approaches based on clinical practice and
      class separability properties. Two-stage classification schemes based on
      hierarchical decomposition boost the classification accuracy from 91% for the
      single-classifier monolithic approach to 99%, matching the theoretical upper
      limit reported in the literature for the accuracy of classifying the dataset.
      Such models are also simpler, achieving up to 47% reduction in the number of
      input variables required, thus reducing the cost and improving the convenience of
      performing the medical diagnostic tests required. Automatic selection of only
      relevant inputs by the simpler abductive network models synthesized provides
      greater insight into the diagnosis problem and the diagnostic value of various
      disease markers. The problem decomposition approach helps plan more efficient
      diagnostic tests and provides improved support for the decision-making process.
      Findings are compared with established guidelines of clinical practice, results
      of data analysis, and outcomes of previous informatics-based studies on the
      dataset.

PMID- 16442852
TI  - Using statistical and knowledge-based approaches for literature-based discovery.
AB  - The explosive growth in biomedical literature has made it difficult for
      researchers to keep up with advancements, even in their own narrow
      specializations. While researchers formulate new hypotheses to test, it is very
      important for them to identify connections to their work from other parts of the
      literature. However, the current volume of information has become a great barrier
      for this task and new automated tools are needed to help researchers identify new
      knowledge that bridges gaps across distinct sections of the literature. In this
      paper, we present a literature-based discovery system called LitLinker that
      incorporates knowledge-based methodologies with a statistical method to mine the
      biomedical literature for new, potentially causal connections between biomedical
      terms. We demonstrate LitLinker's ability to capture novel and interesting
      connections between diseases and chemicals, drugs, genes, or molecular sequences
      from the published biomedical literature. We also evaluate LitLinker's
      performance by using the information retrieval metrics of precision and recall.

PMID- 16442853
TI  - Decision support for acute problems: the role of the standardized patient in
      usability testing.
AB  - For applications that require clinician use while interacting with patients,
      usability testing with standardized patients has the potential to approximate
      actual patient care in a controlled setting. We used hypothetical scenarios and a
      standardized patient to collect quantitative and qualitative results in testing
      an early prototype of a new application, the Acute Respiratory Infection (ARI)
      Smart Form. The standardized patient fit well into the usability testing
      sessions. Clinicians had a positive response to the standardized patients and
      behaved as they normally would during a clinical encounter. Positive findings of
      the ARI Smart Form included that users thought it had impressive functionality
      and the potential to save time. Criticism focused on the visual design, which
      could be streamlined, and navigation, which was difficult in some areas. Based on
      these results, we are modifying the ARI Smart Form in preparation for use in
      actual patient care. Standardized patients should be considered for usability
      testing, especially if an application is to be used during the patient interview.

PMID- 16442854
TI  - A taxonomic description of computer-based clinical decision support systems.
AB  - OBJECTIVE: Computer-based clinical decision support systems (CDSSs) vary greatly
      in design and function. Using a taxonomy that we had previously developed, we
      describe the characteristics of CDSSs reported in the literature. METHODS: We
      searched PubMed and the Cochrane Library for randomized controlled trials (RCTs)
      published in English between 1998 and 2003 that evaluated CDSSs. We coded each
      CDSS using our taxonomy. RESULTS: 58 studies met our inclusion criteria. The 74
      reported CDSSs varied greatly in context of use, knowledge and data sources,
      nature of decision support offered, information delivery, and workflow impact.
      Two distinct subsets of CDSSs were seen: patient-directed systems that provided
      decision support for preventive care or health-related behaviors via mail or
      phone (38% of systems), and inpatient systems targeting clinicians with online
      decision support and direct online execution of the recommendations (18%). 84% of
      the CDSSs required extra staffing for handling CDSS-related input or output.
      CONCLUSION: Reported CDSSs are heterogeneous along many dimensions. Caution
      should be taken in generalizing the results of CDSS RCTs to different clinical or
      workflow settings.

PMID- 16442855
TI  - Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome
      related proteins, DSCR1 and ITSN1.
AB  - Down syndrome (DS) is a genetically-based disorder which results in multiple
      conditions for sufferers. Amongst these is a common early incidence of
      Alzheimer's disease (AD) which usually affects DS individuals by their mid 40s.
      This fact provides a clue that one or more of the genes located on chromosome 21
      may be involved in the onset of AD. Current evidence suggests that endosomal
      disorders may underlie the earliest pathology of AD, preceding the classical
      pathological markers of beta-amyloid plaque deposition and neurofibrillary
      tangles. Therefore, any genes involved in endocytosis and vesicle trafficking
      which are over-expressed in DS are novel candidates in the pathogenesis of AD.
      Intersectin-1 (ITSN1) and Down syndrome candidate region 1 (DSCR1) are two such
      genes. Extensive in vitro data and data from Drosophila indicates that the over
      expression of either of these genes or their products results in inhibition or
      ablation of endocytosis in neuronal as well as non-neuronal cells. This review
      discusses in detail the known and potential roles of ITSN1 and DSCR1 in DS, AD,
      endocytosis and vesicle trafficking.

PMID- 16442856
TI  - Roles of DNA ligase III and XRCC1 in regulating the switch between short patch
      and long patch BER.
AB  - Damaged DNA bases are repaired by base excision repair (BER), which can proceed
      via two pathways: short patch and long patch BER. During the latter, a stretch of
      several nucleotides is replaced by strand displacement DNA synthesis. We recently
      demonstrated that the ATP concentration may govern the decision between these BER
      sub-pathways. Employing a reconstituted BER complex containing among others DNA
      polymerase beta (Pol beta), DNA ligase III (Lig III) and XRCC1, here we show that
      Lig III and XRCC1 are essential mediators of this regulation. XRCC1 stimulates
      Pol beta strand displacement activity and releases inhibition of Pol beta by DNA
      bound Lig III if ligation is prevented. XRCC1 is thus able to strongly promote
      strand displacement and long patch BER under conditions of ATP shortage. If
      sufficient ATP is available, ligation by Lig III prevents strand displacement,
      leading to short patch BER. Ligation-inactive mutants of Lig III do not prevent
      strand displacement by Pol beta under the same conditions. Consequently, the
      preferred use of short patch BER depends on the ligation competence of Lig III.
      Accordingly, lowering the levels of the XRCC1/Lig III complex in HeLa cells using
      siRNA decreases ligation capacity but enhances Pol beta-dependent DNA synthesis.

PMID- 16442857
TI  - Atmnd1-delta1 is sensitive to gamma-irradiation and defective in meiotic DNA
      repair.
AB  - The efficient repair of double-strand breaks (DSBs) in genomic DNA is crucial for
      the survival of all organisms. Mnd1 is suggested to promote the strand invasion
      step during meiotic recombination. We used a forward genetics approach, through
      the search for mutants, to characterize the Arabidopsis homologue of Mnd1. Atmnd1
      null mutants exhibit normal vegetative and flower development. In contrast,
      during prophase I, chromosomes become fragmented resulting in random distribution
      of the fragments between polyads. Male and female meiosis are defective and
      strong accumulation of AtRAD51 was observed in atmnd1-delta1 nuclei. These
      results suggest that similarly to its yeast and animal homologues, AtMnd1 plays a
      role in DSB repair during meiosis. In addition, like its human homologue AtMnd1
      is expressed in somatic cells. AtMnd1 expression is strongly induced by gamma
      rays and null mutants show increased sensibility to gamma-rays. Taken together,
      these results suggest that AtMnd1 is also required for DSB repair in somatic
      cells.

PMID- 16442858
TI  - Female productivity and mortality in early-20th-century Taiwan.
AB  - In late-Qing-dynasty Taiwan (1870-1895), female infanticide and general neglect
      killed over 15% of young girls. During the early years of Japanese rule (1895
      1915), female infanticide was almost completely eliminated and the treatment of
      girls improved. This paper argues that the increase in the willingness to raise
      daughters was due to an increase in adult female productivity. Under Japanese
      rule, female seclusion decreased, female labor market participation greatly
      increased and the custom of foot-binding was ended. These changes increased the
      expected value of raising a daughter relative to raising a son.

PMID- 16442859
TI  - Runx2 regulates the expression of GNAS on SaOs-2 cells.
AB  - Runx2 is a key regulator of osteoblast-specific gene expression and controls the
      expression of multiple target genes during osteoblast differentiation. Although
      some transcriptional targets for Runx2 are known, it is believed that the
      osteogenic action of Runx2 is mediated by additional target genes, and increasing
      studies are performed in order to identify such Runx2-responsive genes. To
      identify genes following the inhibition of Runx2 in osteoblastic cell line, SaOs
      2 was stably transfected with a dominant negative mutant of Runx2 (Deltacbfa1)
      under the control of a strong promoter. Comparison of gene expression patterns by
      differential display on selected SaOs-2 clones allowed us to observe that GNAS
      mRNA which encodes for the Gsalpha protein is overexpressed (5 to 8 fold) in
      cells presenting high levels of Deltacbfa1. This overexpression was also observed
      at the protein level and seemed to be reflected by an increased basal cAMP level.
      Gel shift experiments performed in this study indicate that Runx2 is able to bind
      to the promoter of GNAS, suggesting a direct regulation at the transcriptional
      level. Well-described GNAS mutations like fibrous dysplasia or Albright
      hereditary osteodystrophy are linked to abnormality in osteoblast function, and
      numerous evidences showed that Gsalpha coupled adrenergic receptors increase the
      expression of osteotrophic factors and regulate bone mass. Regulation of Gsalpha
      protein by Runx2 seems to be of particular interest considering the increasing
      evidences on bone metabolism regulation by G proteins.

PMID- 16442860
TI  - Fighting osteoporosis on two fronts.

PMID- 16442863
TI  - Playing to win: video games and the fight against obesity.

PMID- 16442864
TI  - Will you be ready to help when disaster hits?

PMID- 16442865
TI  - Hospital therapeutic diet orders and the Centers for Medicare & Medicaid
      Services: steering through regulations to provide quality nutrition care and
      avoid survey citations.

PMID- 16442866
TI  - Ethical framework for the registered dietitian in decisions regarding
      withholding/withdrawing medically assisted nutrition and hydration.

PMID- 16442867
TI  - Dietary studies in the multi-ethnic Hawaiian population.

PMID- 16442868
TI  - Food preparation and purchasing roles among adolescents: associations with
      sociodemographic characteristics and diet quality.
AB  - OBJECTIVE: To describe adolescent involvement in preparing and shopping for food
      and examine if extent of involvement is related to diet quality. DESIGN: Cross
      sectional study design. Past week frequency of involvement in preparing and
      shopping for food was self-reported on the Project EAT (Eating Among Teens)
      survey. Dietary intake was assessed using the Youth/Adolescent Food Frequency
      Questionnaire. SUBJECTS/SETTING: Middle school and high school students from
      Minneapolis/St Paul, MN, public schools. STATISTICAL ANALYSES PERFORMED:
      Associations between involvement and sociodemographic characteristics were
      examined using cross tabulations. General linear modeling was used to compare
      dietary intakes of adolescents across different levels of involvement in
      preparing and shopping for food. RESULTS: The majority of adolescents reported
      helping prepare dinner (68.6%) and nearly half reported shopping for groceries
      (49.8%) at least once during the past week. Greater involvement in these food
      tasks was related to sex (female), grade level (middle school), race (Asian
      American), socioeconomic status (low), family meal frequency (high), and weight
      status (overweight). Frequency of preparing food was related to lower intakes of
      fat (P<0.01) and higher intakes of fruits and vegetables, fiber, folate, and
      vitamin A. Preparing was related to lower intakes of carbonated beverages among
      female adolescents (P<0.01) and lower intakes of fried foods among male
      adolescents (P<0.01). In contrast, food shopping frequency was related to greater
      consumption of fried foods among female adolescents (P<0.01). CONCLUSIONS:
      Adolescents should be encouraged to help with meal preparation and may benefit
      from interventions and programs that teach skills for cooking and making
      healthful purchasing decisions.

PMID- 16442869
TI  - The need for family meals.

PMID- 16442871
TI  - Survey of herbal use by Kansas and Wisconsin WIC participants reveals moderate,
      appropriate use and identifies herbal education needs.
AB  - OBJECTIVE: To examine herbal use by a sample of low-income, nutritionally
      vulnerable children. DESIGN: Caregivers completed a survey of child and caregiver
      herbal usage practices. SUBJECTS/SETTING: A convenience sample of 2,562
      caregivers to children participating in the Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC) in Kansas and Wisconsin who were
      attending a WIC clinic was selected. WIC project selection was random, with
      stratification for geographic and ethnic representation. STATISTICAL ANALYSES
      PERFORMED: Herbal usage profiles were described with measures of central
      tendency. Groups were compared with a two-tailed independent t test and chi2 for
      continuous and categorical variables, respectively. RESULTS: Child herbal use was
      reported on 917 surveys, representing 1,363 children ranging in age from 1 week
      to 17.5 years; 820 were younger than age 5 years. Herb use was greater among
      Latino children (48.4% vs 31.4%) and caregivers (43.4% vs 37.2%). Caregivers had
      a mean age of 27.8+/-8.32 years and 38.8% (n=994) denoted using herbs. Herbs most
      commonly used by children were aloe vera, chamomile, garlic, peppermint,
      lavender, cranberry, ginger, echinacea, and lemon. Reasons for herbal use
      paralleled recommendations. Family (78.9%) and friends (32.9%) were predominant
      information sources. Herbs with safety issues, such as St John's wort, dong quai,
      and kava were used. Herbal use characteristics did not differ between states, but
      were unique for Latino clients. CONCLUSIONS: Herbal use by WIC children is mostly
      congruent with known indications; however, practices with potential to harm urge
      herbal education in WIC clinics, especially for Latinos.

PMID- 16442870
TI  - Ethnicity and nutrition of adolescent girls in Hawaii.
AB  - OBJECTIVE: To describe the ethnicity and nutrition of adolescent girls in Hawaii.
      DESIGN: This was a cross-sectional survey. SUBJECTS: Girls, aged 9 to 14 years,
      were identified from the membership files of Kaiser Permanente Hawaii, a large
      Hawaii health maintenance organization. MAIN OUTCOME MEASURES: Nutrient and food
      group intakes were compared against recommended intakes, physical activity
      levels, and anthropometric measurements of height, weight, body mass index (BMI),
      and subscapular and iliac skinfold thicknesses. STATISTICAL ANALYSIS PERFORMED:
      Asian girls, girls of mixed ethnicity, and white girls were compared using
      analysis of variance. RESULTS: Although Asian girls weighed the least and were
      the most sedentary, white girls had the lowest BMIs. Mixed ethnicity girls had
      the highest weights, BMIs, and subscapular and iliac skinfold thicknesses. No
      significant differences were found in major macronutrient intake. However, mixed
      ethnicity and Asian girls had lower fiber, iron, folate, and calcium intake than
      white girls. All groups met recommendations for iron intake, whereas none met
      fiber and calcium recommendations. All girls met folate recommendations. No
      differences were found in intakes for tofu, soy, grains, vegetables, or fruit and
      nuts food groups. Mixed ethnicity girls had the highest sweetened carbonated
      beverage intake although overall sugar intake was highest in white girls. Asian
      and mixed ethnicity girls' meat intakes were higher than white girls'. Intakes of
      mixed ethnicity girls more closely resembled those of Asians, although they
      exhibited the highest BMIs. CONCLUSIONS: These data suggest grain, vegetable,
      fruit, and dairy intake should be encouraged as part of a balanced diet for
      adolescent girls in Hawaii.

PMID- 16442872
TI  - Factors associated with the offering and sale of competitive foods and school
      lunch participation.
AB  - OBJECTIVE: The objective of this study was to identify factors that predict
      offering and sale of competitive foods, as well as factors that predict average
      daily participation in school lunch. DESIGN: Surveys were distributed to 271
      school foodservice directors in a random sample of high schools in Pennsylvania
      that were selected to be representative of the entire population of high schools
      in Pennsylvania based on chosen demographic characteristics. SUBJECTS: Two
      hundred twenty-eight school foodservice directors (84%) returned surveys.
      STATISTICAL ANALYSES: Descriptive and multiple regression analyses were done
      using SPSS version 11.5 (2002, SPSS Inc, Chicago, IL). RESULTS: Percentage of
      students eligible for free or reduced-price meals and timing of lunch were
      significant predictors of a la carte sales. Enrollment was negatively associated
      with number of vending machines per student. The number of less nutritious food
      items offered in vending machines and existence of soft drink machines owned by
      soft drink companies, for which the school receives a percent of sales, both
      predicted number of vending machines per student. Enrollment was inversely
      related to average daily participation in school lunch. The percentage of
      students eligible for free/reduced-price meals and enforcement of a policy
      prohibiting parents or students from bringing food into the cafeteria from local
      fast-food establishments positively predicted average daily participation in
      school lunch. CONCLUSIONS: These findings may be useful to school wellness
      councils in developing wellness policies as mandated by the Child Nutrition and
      WIC Reauthorization Act of 2004, as well as in structuring school environments to
      promote more healthful food choices by students.

PMID- 16442873
TI  - Increasing frequency of lower-fat entrees offered at school lunch: an
      environmental change strategy to increase healthful selections.
AB  - OBJECTIVE: A two-phase study was conducted to determine the effect of an
      environmental intervention aimed to increase the selection of low- and moderate
      fat entrees at school. DESIGN: An evaluation of a school-wide intervention
      followed for two semesters. SUBJECTS: Two schools of similar size and demographic
      data were randomly assigned to either intervention or control. Participants were
      the children in these schools. INTERVENTION: In Phase 1, the rotation of existing
      entrees was modified such that one of three entree choices was low or moderate in
      fat. In Phase 2, the number of competing high-fat entrees was reduced from two
      choices to one. MAIN OUTCOME MEASURES: Data were: (a) entree fat content
      (determined by a registered dietitian) and (b) the aggregate entree selections
      compiled from daily selection reports. STATISTICAL ANALYSES PERFORMED: Frequency
      distributions were used to describe entree availability. Two-way analysis of
      variance indicated differences in the mean daily selection of low-, moderate-,
      and high-fat entrees. RESULTS: In Phase 1 in the intervention school, the number
      of days that a low-fat entree was offered increased by 70%, with no increase in
      the rate of selection of the low- or moderate-fat entrees. In Phase 2, both low-
      and moderate-fat entrees were selected at a higher rate in the intervention
      school (32.1% and 26.4%, respectively) than the control school (13.8% and 7.5%,
      respectively), P<0.01. CONCLUSIONS: Increasing the availability of low- and
      moderate-fat entrees is not sufficient to increase their rate of selection.
      However, their rate of selection is increased as the availability of high-fat
      entree choices is reduced.

PMID- 16442874
TI  - Change in protein intake in elderly French people living at home after a
      nutritional information program targeting protein consumption.
AB  - OBJECTIVE: The purpose of the study was to assess the impact of a nutrition
      information program targeting protein consumption in elderly people. DESIGN AND
      INTERVENTION: Participants individually completed a questionnaire on food
      consumption and answered an attitude questionnaire (first survey period). Half of
      the participants (message group) participated in an information program targeting
      protein consumption, whereas the other half (control group) were not given any
      information. Two weeks after the program, both groups participated in the same
      surveys again (second survey period). SUBJECTS: Eighty-two healthy subjects (65
      to 75 years old) living at home participated in this study. STATISTICAL ANALYSES:
      A two-way multivariate analysis of variance, paired t tests, and chi2 tests were
      performed to determine the influence of group (control versus message) and gender
      on the differences in protein consumption and in attitudes between the first and
      second survey periods. RESULTS: In the second survey period, the control group
      participants decreased their protein intake by an average of 0.049 g/lb/day,
      mainly by a reduction in meat product consumption. Conversely, the message group
      participants increased their protein intake by 0.041 g/lb/day, with a greater
      increase for the women (0.059) than the men (0.023 g/lb/day). After the nutrition
      information program, knowledge, perceived control on health, and belief that
      sensory perception decreased with age were higher among the message group
      participants. CONCLUSIONS: Nutrition knowledge and protein intake increased
      significantly among the message group participants. Thus, it is possible to
      change dietary practice and knowledge in elderly individuals by information
      targeting one nutrition message.

PMID- 16442875
TI  - Development and validation of stages-of-change questions to assess consumers'
      readiness to use a food thermometer when cooking small cuts of meat.
AB  - Consumers' readiness to use a food thermometer when cooking small cuts of meat
      was assessed using Prochaska's Transtheoretical Model of Behavior Change. Face,
      content, and concurrent validity were assessed by peer review, cognitive
      interviews, and mail surveys. The self-administered mail survey was sent to two
      groups of Washington and Idaho residents: 1,000 randomly selected consumers (41%
      return rate), and 231 employees and volunteers of Cooperative Extension involved
      in food and nutrition education (60% return rate). Two-stage classification
      questions were compared with a behavior question about thermometer use, and
      validated using Cronbach's if-item-deleted option for alpha. Concurrent validity
      was assessed using cross-tabulation chi2 test. The detailed classification
      question more accurately classified respondents in both Consumer and Extension
      groups. Cronbach's alpha of the detailed question with the behavior question
      showed a consistency level of alpha=.73 compared to alpha=.35 for the simple
      question format. As expected, Consumer and Extension groups differed
      significantly in their stages of change (P<0.0001), verifying concurrent
      validity. We recommend use of the detailed classification question when staging
      persons related to food thermometer use. The process used for development and
      testing can be used to refine instruments for use in other types of
      interventions.

PMID- 16442877
TI  - School competitive food policies: perceptions of Pennsylvania public high school
      foodservice directors and principals.
AB  - The objectives of this study were to describe the extent, nature, and enforcement
      of school competitive food policies in Pennsylvania public high schools and to
      determine if there are differences between school foodservice directors' and
      principals' perceptions of the existence and enforcement of these policies. A
      survey was distributed to 271 school foodservice directors and 100 principals in
      a representative, random sample of high schools. Two hundred twenty-eight school
      foodservice directors (84%) and 79 principals (79%) returned surveys. Descriptive
      statistics, chi2 analyses, and a proportions test were done using SPSS
      statistical software (SPSS base 11.5 for Windows, 2002, SPSS Inc, Chicago, IL).
      Few nutrition policies were reported related to setting nutritional standards for
      competitive foods (0.5% to 15.0%). Respondents' reporting of existence of
      policies not always enforced ranged from 0% to 12.8%. School foodservice
      directors reported uncertainty about existence of several policies outside their
      direct domain, but with potential effect on school meals participation.
      Differences were found between school foodservice directors' and principals'
      reporting of policies, with principals more often reporting policy existence and
      enforcement. These findings suggest the need for communication, both about
      existence of policies and chain of command in enforcement of policies. Given the
      local wellness policy provision of the Child Nutrition and WIC Reauthorization
      Act of 2004, opportunities exist for nutrition professionals to contribute to
      development of policies that influence the nutritional quality of school foods.

PMID- 16442876
TI  - Homocysteine and its determinants in nondialyzed chronic kidney disease patients.
AB  - This cross-sectional study aimed to investigate the prevalence of
      hyperhomocysteinemia, the determinants of plasma total homocysteine
      concentrations, and the relationship of total homocysteine with nutritional
      parameters in a sample of patients with chronic kidney disease (CKD) and not yet
      on dialysis. The study was done with outpatients from the Nephrology Division of
      the Federal University of Sao Paulo and Oswaldo Ramos Foundation. Sixty-six
      patients with CKD (70% male; age 58.6+/-15.6 years [mean+/-standard deviation])
      with moderate to severe renal impairment (creatinine clearance=29.8+/-14.3 mL/min
      [0.5+/-0.24 mL/sec]), clinically stable, and older than 18 years were included. A
      group of 20 healthy subjects from the clinic staff was also studied for reference
      values for plasma homocysteine, folate, and vitamin B-12 concentration. Fasting
      blood samples were collected to determine plasma total homocysteine, folate,
      vitamin B-12, and creatinine. To calculate creatinine clearance, a 24-hour urine
      collection sample was obtained. The assessment of nutritional status included
      anthropometric parameters. Pearson correlation, Mann-Whitney test, and multiple
      linear regression analysis were used for statistical analyses. The main results
      showed that the concentration of total homocysteine in the patients was
      significantly increased compared with the healthy subjects (3.4+/-1.7 vs 1.41+/
      0.42 mg/L [25.4+/-12.2 vs 10.4+/-3.1 micromol/L]; P<0.001). Plasma folate and
      plasma vitamin B-12 were in the normal range and did not differ between patients
      and healthy individuals. A high prevalence of hyperhomocysteinemia (total
      homocysteine >1.89 mg/L [14 micromol/L]) was found in the patients (89%). Plasma
      total homocysteine did not correlate with any of the nutritional parameters
      studied and did not differ between patients in terms of whether they were using
      or not using folic acid supplementation (3.07+/-1.09 vs 3.55+/-1.78 mg/L [22.7+/
      8.1 vs 26.3+/-13.2 micromol/L]; P=0.47), although plasma folate was significantly
      higher in the supplemented group (12.6+/-3.0 vs 8.0+/-3.6 ng/mL [28.5+/-6.8
      nmol/L vs 18.1+/-8.2 nmol/L]; P<0.001). According to the multiple regression
      analysis, the determinants of total homocysteine were only plasma folate, plasma
      vitamin B-12, and creatinine clearance (r2=0.20). In conclusion, a high
      prevalence of hyperhomocysteinemia was found in our sample of nondialyzed
      patients with CKD. The determinants of total homocysteine levels were plasma
      folate, plasma vitamin B-12, and creatinine clearance. No association between
      nutritional parameters and total homocysteine was observed.

PMID- 16442878
TI  - "You had peas today?": a pilot study comparing a Head Start child-care center's
      menu with the actual food served.
AB  - This study explored the types of food served at a Head Start child-care center
      compared with that center's monthly menus. The study design was direct
      observation of the food provided by a Head Start center throughout the school day
      (Monday through Friday; 8:45 am to 2:30 pm) from January 4 to June 20, 2002, and
      analysis of this center's monthly menus. The numbers of meals directly observed
      for each type of meal service were: breakfast (n=96), lunch (n=95), and afternoon
      snack (n=78). These meals were compared with six monthly menus. Of the 269 meals
      and snacks compared, only three breakfast meals and an "ethnic day" matched the
      meals described on the provided menu. These findings illustrate that this
      center's menu was not consistently followed and therefore could not be used as an
      estimate of the preschoolers' intake or used as an educational or informational
      tool for parents/caregivers. Future research should verify how common these
      findings are among other Child and Adult Care Food Program child-care centers.
      Results may provide direction for development of the US Department of
      Agriculture's Child and Adult Care Food Program training for foodservice workers
      and educational materials focusing on menu development, appropriate
      substitutions, and the importance of using menus as a nutrition education tool.

PMID- 16442880
TI  - Position of the American Dietetic Association: Agricultural and food
      biotechnology.
AB  - It is the position of the American Dietetic Association that agricultural and
      food biotechnology techniques can enhance the quality, safety, nutritional value,
      and variety of food available for human consumption and increase the efficiency
      of food production, food processing, food distribution, and environmental and
      waste management. The American Dietetic Association encourages the government,
      food manufacturers, food commodity groups, and qualified food and nutrition
      professionals to work together to inform consumers about this new technology and
      encourage the availability of these products in the marketplace.

PMID- 16442879
TI  - Implementation of dietitian recommendations for enteral nutrition results in
      improved outcomes.
AB  - A primary role of the registered dietitian (RD) is to assess nutritional needs of
      patients in states of physiological stress and illness and to recommend changes
      to diet and tube feedings when warranted. However, implementation of changes is
      dependent upon the physician accepting the recommendations of the RD. This study
      evaluated outcomes of two groups of enterally fed patients in a long-term acute
      care facility in northwest Louisiana: (a) those for whom the physician accepted
      RD recommendations; and (b) those for whom the physician did not accept RD
      recommendations. Data showed that physician-prescribed enteral formulas provided
      10.0% less kilocalories and 7.8% less protein than the RD-assessed needs. t tests
      showed that when RD recommendations were implemented, patients had a
      significantly shorter length of stay (28.5+/-1.8 vs 30.5+/-4.8 days, P<0.05), as
      well as significantly improved albumin (0.13+/-0.17 vs -0.44+/-0.21 g/dL [1.3+/
      1.7 vs -4.4+/-2.1 g/L], P<0.05) and weight gains (0.51+/-0.1 vs -0.42+/-0.2%,
      P<0.05) when compared to those who continued with physician's orders. These data
      suggest that if RDs had the authority to write nutrition orders and provide early
      nutrition intervention, patient care would improve.

PMID- 16442881
TI  - Dietetics salaries on the rise.

PMID- 16442882
TI  - What are some of the major changes in the 2005 Food Code?

PMID- 16442883
TI  - Potential mechanisms between atrial dilatation and atrial fibrillation.

PMID- 16442885
TI  - Determinants of referral to cardiac rehabilitation programs in patients with
      coronary artery disease: a systematic review.
AB  - BACKGROUND: Despite the documented efficacy of cardiac rehabilitation (CR), a
      minority of patients with diagnosed coronary artery disease are referred.
      Although referral is a necessary step in the promotion of CR uptake, little is
      known about its determinants. PURPOSE: The objective of this paper was to
      systematically review the available literature on factors predicting referral of
      patients to CR to appraise both their relative impact and consistency across
      studies. METHODS: Studies were identified by searching MEDLINE (1966-2003),
      CINAHL (1982-2003), HealthSTAR (1975-2003), EMBASE (1966-2003), and The Cochrane
      Library Controlled Trials. Search terms were "myocardial infarction," "acute
      myocardial infarction," "coronary artery disease," combined with
      "rehabilitation," "cardiac rehabilitation," "secondary prevention," "exercise
      training," "referral," and/or "consultation." Forty-five studies were identified
      and independently assessed by 2 reviewers using predetermined eligibility
      criteria. RESULTS: Ten published observational studies (1999-2004) including
      30,333 coronary artery disease patients were selected. Determinants of referral
      to CR were grouped as sociodemographic, health status, and health care system
      factors. Major predictors were English speaking (RR 9.56, 95% CI 2.18-41.93),
      prior myocardial infarction (RR 2.73, 95% CI 1.69-4.42), being admitted to
      hospitals providing CR (RR 5.35, 95% CI 4.04-7.10), and having insurance coverage
      (RR 2.94, 95% CI 1.13-7.66). CONCLUSION: This review highlights disparities in
      referral to CR and reveals a treatment gap in the secondary prevention of
      cardiovascular disease. Precise estimates of the impact of all factors on
      referral are not possible, but some hierarchies and potential priorities for
      action are evident.

PMID- 16442886
TI  - Subgroup analyses in therapeutic cardiovascular clinical trials: are most of them
      misleading?
AB  - BACKGROUND: Treatment decisions in clinical cardiology are directed by results
      from randomized clinical trials (RCTs). We studied the appropriateness of the use
      and interpretation of subgroup analysis in current therapeutic cardiovascular
      RCTs. METHODS: We reviewed main reports of phase 3 cardiovascular RCTs with at
      least 100 patients, published in 2002 and 2004, and from major journals
      (Circulation, J Am Coll Cardiol, Am Heart J, Am J Cardiol, N Engl J Med, Lancet,
      JAMA, BMJ, Ann Intern Med). Information on subgroups included prespecification,
      number, interaction test use, significant subgroups found, and emphasis on
      findings. We examined appropriateness of reporting and differences according to
      sample size, overall trial result, and CONSORT adoption. RESULTS: We selected 63
      RCTs, with a median of 496 (range 100-15,245) patients. Thirty-nine RCTs were
      reported with subgroup analyses and 26 with > 5 subgroups. No trial was
      specifically powered to detect subgroup effects, and only 14 RCTs were reported
      with fully prespecified subgroups. Only 11 RCTs were reported with interaction
      tests. Furthermore, 21 RCTs were reported with claims of significant subgroups
      and 15 with equal or more emphasis to subgroups than to the overall results.
      Subgroup analyses in large RCTs (> 500 patients) were reported more often than in
      small ones (24/30 vs 15/33, P = .005). No differences were found according to
      overall result (positive/negative) or CONSORT adoption. CONCLUSIONS: Subgroup
      analyses in recent cardiovascular RCTs were reported with several shortcomings,
      including a lack of prespecification and testing of a large number of subgroups
      without the use of the statistically appropriate test for interaction. Reporting
      of subgroup analysis needs to be substantially improved because emphasis on these
      secondary results may mislead treatment decisions.

PMID- 16442887
TI  - Cardiovascular magnetic resonance in the follow-up of patients with corrected
      tetralogy of Fallot: a review.
AB  - Cardiovascular magnetic resonance (CMR) is becoming an important tool in the
      clinical management of patients with congenital heart disease. Because of the
      diverse problems patients may face after initial correction for tetralogy of
      Fallot and the large amount of CMR techniques that can be applied, creating a
      patient-orientated imaging protocol is a difficult issue. Although it is still
      not certain what the impact of some parameters, provided by CMR, should be on
      clinical decision making, new techniques are being developed and applied. In this
      report, we review the current clinical issues in patients with tetralogy of
      Fallot and review the current implication and limitations of CMR in this patient
      category.

PMID- 16442888
TI  - Are statins created equal? Evidence from randomized trials of pravastatin,
      simvastatin, and atorvastatin for cardiovascular disease prevention.
AB  - BACKGROUND: The relative efficacy of different statins for long-term
      cardiovascular prevention remains largely undetermined. METHODS: Using adjusted
      indirect comparison, we compared 3 statins (pravastatin, simvastatin, and
      atorvastatin) based on published randomized placebo-controlled trials for long
      term cardiovascular prevention. A systematic literature search between 1980 and
      2004 was conducted. Randomized placebo-controlled trials of the 3 statins, which
      studied cardiovascular diseases or death as the outcome, enrolled > or = 1000
      participants, and had > or = 1-year follow-up, were included. Trials were grouped
      according to the statin under study. A pooled relative risk (RR) was derived from
      each set of trials using a random-effects model. Adjusted indirect comparisons
      using pooled RRs were made between statins with regard to prespecified clinical
      outcomes. RESULTS: Eight placebo-controlled trials met the inclusion criteria,
      including 4 pravastatin trials (n = 25,572), 2 simvastatin trials (n = 24,980),
      and 2 atorvastatin trials (n = 13,143). All trials had a similar degree of lipid
      reduction. Graphical and statistical assessments showed minimal heterogeneity in
      the trials' effect sizes. Adjusted indirect comparisons did not reveal a
      statistically significant difference between statins in reducing fatal coronary
      heart disease and nonfatal myocardial infarctions (simvastatin vs pravastatin: RR
      0.93 [95% CI 0.84-1.03]; atorvastatin vs simvastatin: RR 0.84 [95% CI 0.66-1.08];
      atorvastatin vs pravastatin: RR 0.79 [95% CI 0.61-1.02]). We were unable to
      detect differences either in outcomes for fatal and nonfatal strokes, all
      cardiovascular deaths, and all-cause mortality. CONCLUSION: Evidence from
      published statin randomized placebo-controlled trials suggests that pravastatin,
      simvastatin, and atorvastatin, when used at their standard dosages, show no
      statistically significant difference in their effect on long-term cardiovascular
      prevention.

PMID- 16442889
TI  - Homocysteine-lowering trials for prevention of cardiovascular events: a review of
      the design and power of the large randomized trials.
AB  - BACKGROUND: Dietary supplementation with folic acid and vitamin B12 lowers blood
      homocysteine concentrations by about 25% to 30% in populations without routine
      folic acid fortification of food and by about 10% to 15% in populations with such
      fortification. In observational studies, 25% lower homocysteine has been
      associated with about 10% less coronary heart disease (CHD) and about 20% less
      stroke. METHODS: We reviewed the design and statistical power of 12 randomized
      trials assessing the effects of lowering homocysteine with B-vitamin supplements
      on risk of cardiovascular disease. RESULTS: Seven of these trials are being
      conducted in populations without fortification (5 involving participants with
      prior CHD and 2 with prior stroke) and 5 in populations with fortification (2
      with prior CHD, 2 with renal disease, and 1 with prior stroke). These trials may
      not involve sufficient number of vascular events or last long enough to have a
      good chance on their own to detect reliably plausible effects of homocysteine
      lowering on cardiovascular risk. But, taken together, these 12 trials involve
      about 52,000 participants: 32,000 with prior vascular disease in unfortified
      populations and 14,000 with vascular disease and 6000 with renal disease in
      fortified populations. Hence, a combined analysis of these trials should have
      adequate power to determine whether lowering homocysteine reduces the risk of
      cardiovascular events within just a few years. CONCLUSION: The strength of
      association of homocysteine with risk of cardiovascular disease may be weaker
      than had previously been believed. Extending the duration of treatment in these
      trials would allow any effects associated with prolonged differences in
      homocysteine concentrations to emerge. Establishing a prospective meta-analysis
      of the ongoing trials of homocysteine lowering should ensure that reliable
      information emerges about the effects of such interventions on cardiovascular
      disease outcomes.

PMID- 16442890
TI  - Rationale and design of a randomized controlled trial to assess the safety and
      efficacy of cardiac resynchronization therapy in patients with asymptomatic left
      ventricular dysfunction with previous symptoms or mild heart failure--the
      REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction
      (REVERSE) study.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, reduces
      heart failure (HF)-related hospitalizations, and reverses left ventricular
      remodeling in some patients with moderate to severe HF and ventricular
      dyssynchrony defined by a prolonged QRS duration. The effects of CRT on HF
      outcomes in patients with asymptomatic left ventricular dysfunction (ALVD) or
      mild HF remain to be determined. METHODS: The REsynchronization reVErses
      Remodeling in Systolic left vEntricular dysfunction (REVERSE) study is a
      prospective, multicenter, randomized, double-blind, parallel, controlled clinical
      trial designed to establish whether CRT combined with optimal medical treatment
      can attenuate HF disease progression compared with optimal medical treatment
      alone in patients with ALVD +/- New York Heart Association class I American
      College of Cardiology/American Heart Association stage C or New York Heart
      Association class II HF, QRS duration > or =120 milliseconds, left ventricular
      ejection fraction < or =0.40, and left ventricular end-diastolic diameter > or
      =55 mm. The primary end point is the HF clinical composite response and left
      ventricular end-systolic volume index is the first-order secondary end point.
      Approximately 500 patients from 100 centers in the United States, Canada, and
      Europe will be randomized to CRT versus no CRT. The follow-up is 5 years in total
      with the primary and first secondary end points reported at 12 months. Enrollment
      began in September 2004 and is expected to be completed in 2006. CONCLUSION:
      REVERSE will assess the safety and efficacy of CRT in patients with ALVD or mild
      HF and electrocardiographic evidence of ventricular dyssynchrony.

PMID- 16442892
TI  - External validation of a percutaneous coronary intervention mortality prediction
      model in patients with acute coronary syndromes.
AB  - BACKGROUND: The recently published Michigan outcome prediction model (MM) for
      inhospital mortality was developed and validated on a series of consecutive
      patients undergoing percutaneous coronary intervention (PCI). Our purpose was to
      externally validate the performance of the MM in 2 separate cohorts of patients
      with acute coronary syndrome (ACS) undergoing PCI in Canada. METHODS: A
      validation of the MM and development of an extended MM were performed on data
      describing 10,050 patients from the APPROACH prospective cohort study between
      January 1995 and December 2000. Performance of both models was assessed on an
      external data set of 3259 PCI cases from the British Columbia Cardiac Registries.
      Only patients with a diagnosis of ACS were included in the study. RESULTS: The
      original MM predicted death rates ranging from 0.1% to 60.6%, but lacked accuracy
      to predict inhospital mortality as severity increased. The extended MM predicted
      death rates more widely from 0.0% to a high of 91.0% with better accuracy to
      predict inhospital death in patients with ACS undergoing PCI. The areas under the
      receiver operating characteristic curve for the MM and the extended MM on the
      external validation data set were 0.93 and 0.95, respectively. CONCLUSION: The MM
      predicts death after PCI in patients with ACS and identifies a clear gradient of
      risk. However, the enhanced MM developed specifically for the subset of patients
      with ACS demonstrated better prediction and cross-validated performance. These
      prediction rules can be useful for risk-adjustment analyses and for
      prognostication for individual patients.

PMID- 16442893
TI  - Cardiac tamponade in the fibrinolytic era: analysis of >100,000 patients with ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Cardiac tamponade is a life-threatening complication of acute
      myocardial infarction (MI). Data on the incidence, risk factors, and outcome of
      tamponade in patients with acute MI in the fibrinolytic era are limited. METHODS:
      Data from a combined clinical trials database of ST-segment elevation MI were
      used to evaluate the incidence of cardiac tamponade, baseline characteristics,
      and outcomes in patients with and without tamponade. Univariable and
      multivariable analyses assessed the relationship between patient characteristics
      and tamponade development, and the influence of tamponade on mortality. RESULTS:
      Of 102,060 patients, 865 (0.85%) developed isolated cardiac tamponade during
      initial hospitalization. Patients with tamponade were older (median 71.9 vs 61.6
      years, P < .001), were more likely to be female (54.0% vs 25.1%, P < .001), were
      more likely to have an anterior MI (61.9% vs 41.5%, P < .001), and had a longer
      time from symptom onset to reperfusion (median 3.5 vs 2.8 hours, P < .001) than
      those without tamponade. Multivariable analyses identified increasing age,
      anterior MI location, female sex, and increased time from symptom onset to
      treatment as significant independent predictors of tamponade. Patients with
      tamponade had an increased death rate at 30 days (hazard ratio 7.9, 95% CI 4.7
      13.5). CONCLUSION: Cardiac tamponade occurs in < 1% of patients with fibrinolytic
      treated acute MI and is associated with increased 30-day mortality. Time from
      symptom onset to treatment strongly predicted the development of tamponade,
      underscoring the need for continued efforts to increase speed to treatment in
      acute MI.

PMID- 16442894
TI  - Evaluating the performance of the Global Registry of Acute Coronary Events risk
      adjustment index across socioeconomic strata among patients discharged from the
      hospital after acute myocardial infarction.
AB  - BACKGROUND: Cardiac risk-adjustment indices for acute coronary syndromes have
      important clinical and research applications, especially if proven to be valid
      and robust across heterogeneous socioeconomically diverse populations. The
      objective of this study was to validate the Global Registry of Acute Coronary
      Events (GRACE) risk-adjustment index for 6-month all-cause mortality across
      socioeconomic strata. METHODS: The study cohort consisted of patients who were
      enrolled in the SESAMI study and discharged alive from the hospital between
      December 1, 1999, and February 28, 2003. Socioeconomic information was obtained
      through self-report. Hospital chart abstraction was used to ascertain clinical
      detail required for the derivation of the GRACE risk index. Six-month mortality
      rates were obtained through data linkage using encrypted health card numbers. The
      accuracy (c-statistic) and calibration (Hosmer-Lemeshow) characteristics of the
      GRACE risk index were generated using logistic regression across income and
      education strata. RESULTS: Predicted and observed mortality rates were
      significantly higher among patients of lower incomes and education (ie, observed
      6-month mortality: 5.1% vs 1.8% among low income vs high income patients,
      respectively, P < .0001; 4.6% vs 2.9% among low-educated vs highly educated
      patients, respectively, P = .02). The predicted 6-month mortality as derived
      using GRACE closely mirrored observed mortality rates with strong accuracy and
      precision (c-statistic = 0.80 for the overall cohort and within each income and
      education strata; Hosmer-Lemeshow goodness-of-fit test was not significant within
      each income and education strata). CONCLUSION: The GRACE risk score for 6-month
      all-cause mortality is an accurate, well-calibrated, and robust predictor across
      socioeconomic strata and can be used as a valid risk-adjustment index when
      examining socioeconomic-mortality differences after acute MI.

PMID- 16442895
TI  - Acute myocardial infarction: clinical characteristics and plaque morphology
      between expansive remodeling and constrictive remodeling by intravascular
      ultrasound.
AB  - BACKGROUND: According to recent intravascular ultrasound (IVUS) studies,
      expansive remodeling (ER) at the culprit lesion has been observed in almost 50%
      of patients with acute coronary syndrome and constrictive remodeling (CR) in 30%.
      The purpose of this study is to investigate the difference between ER and CR at
      the culprit lesion in patients with acute myocardial infarction (AMI). METHODS
      AND RESULTS: Preinterventional IVUS images of 73 patients with AMI were
      identified. The remodeling index (RI) was defined as the ratio of the external
      elastic membrane (EEM) areas at the culprit lesion to the EEM areas at the
      proximal reference site. Expansive remodeling was defined as an RI > 1.05; CR, as
      an RI < 0.95. In patients with AMI, 40 patients (55%) showed ER on IVUS, whereas
      CR was observed in 18 patients (25%). Patients with ER were significantly older
      than those with CR (P < .005). The frequency of the presence of calcifications
      was higher in patients with ER than in those with CR (P < .0005). In patients
      with AMI with ER, soft plaque with small calcium was the most frequent (58%).
      Multivariate analysis revealed that age and the presence of calcifications
      remained as independent predictors of ER. CONCLUSIONS: These findings suggest
      that ER relates to old age and calcification, and CR may contribute to early
      plaque progression than ER in patients with AMI.

PMID- 16442896
TI  - Risk factors for stroke after acute coronary syndromes in the Orbofiban in
      Patients with Unstable Coronary Syndromes--Thrombolysis In Myocardial Infarction
      (OPUS-TIMI) 16 study.
AB  - BACKGROUND: Previous reports have associated acute coronary syndromes (ACSs) with
      cerebrovascular disease but in general have not included long-term patient follow
      up or have not analyzed ischemic and hemorrhagic cerebrovascular events
      separately. METHODS: We analyzed stroke outcomes from the OPUS-TIMI 16 study, a
      multicenter, randomized, placebo-controlled trial. Patients were randomized to
      aspirin plus either orbofiban or placebo and followed for up to 1 year.
      Cerebrovascular events were prospectively identified and classified by a
      committee of cardiologists and neurologists blinded to treatment assignment.
      RESULTS: During 10 months of follow-up, there were 150 (1.5%) patients with
      cerebrovascular events. Risk factors for ischemic stroke (n = 67) and transient
      ischemic attack (TIA) (n = 44) were age, prior ischemic stroke, history of
      hypertension, and increased heart rate. Prior ischemic stroke and history of
      hypertension were not risk factors for 30-day ischemic stroke or TIA. Risk
      factors for intracranial hemorrhage (ICH) (n = 14) were age, history of
      hypertension, history of TIA, and coronary angiography with evidence of coronary
      artery disease. Compared with placebo, treatment with orbofiban was associated
      with a nonsignificant increased risk of ischemic stroke or TIA (HR 1.15, 95% CI
      0.76-1.74, P = .51) and ICH (HR 1.25, 95% CI 0.39-4.00, P = .70). CONCLUSIONS:
      The overall incidence of cerebrovascular events after ACS was highest in the
      first 30 days then declined; risk factors for cerebrovascular events may be
      different in the different periods. Orbofiban, despite no significant excess risk
      of ICH, was not effective in preventing ischemic stroke or TIA.

PMID- 16442897
TI  - Glucose-insulin-potassium infusion in acute myocardial infarction: a hemodynamic
      study.
AB  - BACKGROUND: In this study, we investigated whether adjunction of glucose-insulin
      potassium (GIK) infusion to primary percutaneous coronary intervention (PCI)
      affects hemodynamics in patients with an acute myocardial infarction. METHODS:
      Hemodynamic measurements were performed in a subset of patients (n = 81) in the
      GIPS 2, starting immediately after PCI and continued for 12 hours. RESULTS:
      Cardiac index values were stable in both groups. During the first measurements,
      diastolic pulmonary artery pressure and the pulmonary capillary wedge pressure
      (PCWP) were significantly higher in the non-GIK group (diastolic pulmonary artery
      pressure 15 +/- 5 vs 18 +/- 7 mm Hg, P = .028 and PCWP 14 +/- 6 vs 18 +/- 7 mm
      Hg, P = .030). There was a decrease in PCWP from 18 +/- 7 to 15 +/- 6 mm Hg in
      the non-GIK group during the first 6 hours, whereas the pressures remained at 14
      +/- 6 mm Hg in the GIK group. This difference in pattern of change did not reach
      statistical significance in the analysis of the interaction of PCWP by GIK group
      (P = .065). CONCLUSIONS: Glucose-insulin-potassium infusion as adjunctive therapy
      to PCI in patients with acute myocardial infarction, without overt signs of heart
      failure, did not negatively affect hemodynamics.

PMID- 16442898
TI  - Age-related differences in the management and outcome of patients with acute
      coronary syndromes.
AB  - BACKGROUND: Age-related differences in patients with an acute coronary syndrome
      (ACS) have not been well characterized in prior observational studies that often
      included only certain age groups or subjects with myocardial infarction (MI).
      METHODS: We stratified 4627 patients admitted with an ACS across 9 provinces
      between 1999 and 2001 enrolled in the Canadian ACS Registry into 3 age groups (<
      65, 65-74, and > or = 75 years) to evaluate differences in clinical
      characteristics, management, and 1-year outcome. RESULTS: Older patients more
      frequently had previous angina, MI, or heart failure and were less likely to have
      positive cardiac markers, ST elevation, and Q-wave MI or to receive
      thrombolytics, beta-blockers, and cholesterol-lowering and antiplatelet agents in
      hospital, at discharge, and at 1 year. In multivariable analyses controlling for
      patient factors, every decade increase in age was independently associated with
      reduced use of coronary angiography (odds ratio [OR] 0.79, 95% CI 0.74-0.84, P <
      .001) and percutaneous coronary intervention (OR 0.88, 95% CI 0.81-0.95, P =
      .001). When adjusted for validated clinical prognosticators and differences in
      management, every decade of age increment independently predicted an increased
      risk of death at 1 year (OR 1.87, 95% CI 1.66-2.12, P < .001). CONCLUSIONS:
      Across the broad spectrum of ACS, elderly patients had more complex comorbidities
      and worse outcome, yet they were less likely to undergo revascularization or to
      receive acute and long-term evidence-based medications. Our findings emphasize
      the ongoing need to better define and promote optimal therapeutic regimens for
      elderly patients with ACS.

PMID- 16442899
TI  - Predicting a late positive serum troponin in initially troponin-negative patients
      with non-ST-elevation acute coronary syndrome: clinical predictors and validated
      risk score results from the TIMI IIIB and GUSTO IIA studies.
AB  - BACKGROUND: Troponin testing is useful for evaluating patients with non-ST
      segment elevation acute coronary syndromes (NSTE ACS); however, a significant
      percentage of patients are troponin negative at presentation and develop late
      rise of the marker. METHODS: Patients in the TIMI IIIB study were assessed with
      respect to their troponin I (TnI) status at presentation and 12 hours.
      Multivariable analysis identified independent clinical factors associated with
      TnI rise at 12 hours among subjects initially TnI negative. A score predicting
      late TnI rise in TIMI IIIB was developed using these factors and validated among
      patients in the GUSTO IIA study. RESULTS: Of 1342 subjects in TIMI IIIB, 200
      (14.9%) were negative at baseline, but developed an elevated TnI (> or = 0.4
      ng/mL) at 12 hours. Six independent predictors of late TnI rise were identified:
      ST-segment deviation (odds ratio [OR] 3.52, 95% CI 2.38-5.23, P < .001),
      presentation < 8 hours from symptom onset (OR 2.91, 95% CI 1.92-4.40, P < .001),
      no prior percutaneous coronary intervention (OR 2.88, 95% CI 1.54-5.39, P =
      .001), no prior beta-blocker use (OR 1.74, 95% CI 1.15-2.63, P = .008),
      unheralded angina (OR 1.65, 95% CI 1.12-2.42, P = .01), and a history of
      myocardial infarction (OR 1.59, 95% CI 1.06-2.37, P = .02). ST deviation,
      presentation < 8 hours from symptoms, and no prior percutaneous coronary
      intervention were given a score of 2 points, whereas a score of 1 point was
      assigned to the other factors. Among baseline TnI-negative patients, a rising
      score was paralleled by an increasing prevalence of late TnI rise from 0% (with a
      score of 0) to 69% (with a score of 9) (P < .001). In confirmation, the score was
      able to similarly predict late troponin T rise among 855 patients in the GUSTO
      IIA study (P < .0001). CONCLUSION: Development of late troponin rise is common in
      non-ST-segment elevation acute coronary syndromes. Six easily ascertained
      variables may be used to identify those at higher risk for late rise in troponin
      levels after an initially negative presentation.

PMID- 16442900
TI  - Type D personality and diabetes predict the onset of depressive symptoms in
      patients after percutaneous coronary intervention.
AB  - BACKGROUND: Depression is common in cardiac patients and has been associated with
      adverse clinical outcome. However, little is known about predictors of the onset
      of depressive symptoms. We examined predictors of the onset of depressive
      symptoms at 12 months post-percutaneous coronary intervention (PCI) in patients
      treated in the drug-eluting stent era. METHODS: Unselected patients, free from
      depressive symptoms at 6 months with a depression score at 12 months treated with
      PCI with either drug-eluting or bare stent implantation as part of the RESEARCH
      registry qualified for inclusion in the current study. Patients completed the
      Hospital Anxiety and Depression Scale at 6 and 12 months and the Type D
      Personality Scale (DS14) at 6 months post-PCI. Six months was used as the
      baseline assessment. RESULTS: Of 542 patients, 41 (8%) had developed significant
      depressive symptoms at 12 months. The occurrence of a new cardiac event between 6
      and 12 months post-index event did not influence the incidence of depressive
      symptoms at 12 months. Depressive patients were more likely to have a type D
      personality (34% vs 16%, P = .003) and diabetes (24% vs 11%, P = .01) than
      nondepressive patients. Type D personality (odds ratio 3.04, 95% CI 1.50-6.16)
      and diabetes (odds ratio 2.75, 95% CI 1.25-6.05) were independent predictors of
      the onset of depressive symptoms 12 months post-PCI in adjusted analyses. In
      patients with neither risk factors (type D or diabetes), the incidence of
      depression was 5.1% with the incidence more than doubling to 13.2% and 30% for
      each additional risk factor. CONCLUSIONS: Type D personality and diabetes
      comprise risk factors for the onset of depressive symptoms post-PCI. In clinical
      practice, patients with these risk factors should be identified and considered
      for psychosocial intervention targeting depression to enhance secondary
      prevention.

PMID- 16442901
TI  - Effects of exercise training on 5 inflammatory markers associated with
      cardiovascular risk.
AB  - BACKGROUND: Cross-sectional studies suggest that regular exercise has anti
      inflammatory effects, leading to lower levels of several proatherogenic
      inflammatory markers. However, this has yet to be confirmed by randomized
      prospective trials. We performed a randomized controlled trial to assess whether
      exercise training decreases levels of 5 inflammatory markers linked to future
      cardiovascular risk: white blood cell count, fibrinogen, C-reactive protein,
      soluble intercellular adhesion molecule 1, and soluble CD40 ligand. METHODS: One
      hundred fifty-two healthy female smokers were randomized to either 12 weeks of
      exercise training or health education as part of a smoking cessation program.
      Smoking was held steady for the first 6 weeks, and thereafter, smoking cessation
      was actively attempted. One hundred four participants completed 6 weeks, and 88
      completed 12 weeks. Fitness and circulating inflammatory marker levels were
      measured at baseline, 6 weeks, and 12 weeks. To avoid potential confounding from
      changes in smoking exposure during the second 6 weeks of the trial, the primary
      end point was change in inflammatory marker levels from baseline to 6 weeks.
      Change in inflammatory markers from baseline to 12 weeks was a secondary end
      point. RESULTS: At baseline, greater physical fitness was associated with lower
      white blood cell, fibrinogen, and C-reactive protein levels, but these
      associations were not statistically significant after adjusting for body mass
      index (P > .1 for all). Fitness improved significantly in the exercise group at
      both 6 and 12 weeks. However, there were no differences in levels of any
      inflammatory marker between the exercise and control groups at either 6 weeks
      (primary end point) or 12 weeks (secondary end point) (P > .05 for all
      comparisons). CONCLUSION: In female smokers, baseline associations between
      fitness and inflammatory markers were largely attributable to differences in body
      fat; regular exercise did not reduce levels of any of the inflammatory markers
      studied despite a significant improvement in fitness at both 6 and 12 weeks.

PMID- 16442902
TI  - Alcohol consumption, atherosclerotic progression, and prognosis among patients
      with coronary artery bypass grafts.
AB  - BACKGROUND: Although moderate drinking has been associated with lower mortality
      among patients after myocardial infarction, its relationship with prognosis and
      graft obstruction among patients with coronary artery bypass grafts is unknown.
      METHODS: We studied 1351 patients enrolled in the Post-CABG trial, who had
      undergone coronary bypass surgery 1 to 11 years before entry. Participants were
      randomly assigned to lovastatin in low or high doses and to low-dose warfarin or
      placebo in a factorial design. Participants underwent coronary angiography at
      baseline and after a mean follow-up of 4.3 years and were followed up for a
      composite end point of death, myocardial infarction, stroke, bypass surgery, or
      angioplasty. We categorized reported weekly alcohol intake as abstention (<1
      drink), light (1-6 drinks), moderate (7-13 drinks), and heavier (> or =14
      drinks). RESULTS: During follow-up, 238 participants sustained a clinical event.
      Moderate drinking was associated with a trend toward both fewer clinical events
      (hazard ratio 0.7, 95% CI 0.4-1.1) and less angiographic progression (odds ratio
      0.7, 95% CI 0.5-1.1), although neither of these effects were statistically
      significant. High-density lipoprotein cholesterol appeared to account for one
      third of the trend toward lower risk among moderate drinkers. CONCLUSION: We did
      not demonstrate statistically significant differences in prognosis according to
      alcohol intake in this study, although there were inverse trends between moderate
      drinking and both morbidity and graft progression of a magnitude similar to
      studies in other populations. Larger studies of alcohol intake among patients
      with coronary artery bypass grafts are needed.

PMID- 16442903
TI  - Randomized evaluation of the efficacy of enoxaparin versus unfractionated heparin
      in high-risk patients with non-ST-segment elevation acute coronary syndromes
      receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Long-term results of
      the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome
      Treatment (INTERACT) trial.
AB  - BACKGROUND: Patients with high-risk non-ST-segment elevation acute coronary
      syndromes (NSTE ACS) benefit from the early administration of aspirin, a small
      molecule glycoprotein IIb/IIIa inhibitor such as eptifibatide, and heparin. The
      INTERACT trial demonstrated that in high-risk patients with ACS receiving aspirin
      and eptifibatide, the use of enoxaparin compared with unfractionated heparin
      (UFH) was associated with less bleeding, less early myocardial ischemia, and
      improved 30-day outcomes. OBJECTIVE: The aim of our study was to determine
      whether the short-term benefits of enoxaparin compared with UFH observed in high
      risk patients with NSTE ACS are maintained over a prolonged period of follow-up.
      METHODS: Six hundred thirty-nine patients that were representative of the total
      population of subjects in the INTERACT trial were followed up for a median period
      of 2.5 years. RESULTS: In this group, the early benefit of enoxaparin was
      maintained. The incidence of death or myocardial infarction at the time of long
      term follow-up was 39% lower in patients receiving enoxaparin compared with those
      who received UFH (8.9% vs 14.7%, P = .024). There was no difference in the
      frequency of cardiac catheterization in the groups receiving either enoxaparin or
      UFH. CONCLUSIONS: The early treatment of high-risk patients with NSTE ACS
      receiving aspirin and eptifibatide with enoxaparin is associated with early
      outcome benefits that are sustained over a prolonged follow-up period. This trial
      supports the concept that early treatment directed against platelet and thrombin
      formation is associated with better short- and long-term outcomes.

PMID- 16442904
TI  - Efficacy of transesophageal echocardiography-guided cardioversion of patients
      with atrial fibrillation at 6 months: a randomized controlled trial.
AB  - BACKGROUND: Electrical cardioversion in patients with atrial fibrillation (AF) is
      associated with an increased risk of stroke. We compared a transesophageal
      echocardiography (TEE)-guided strategy with a conventional strategy in patients
      with AF > 2 days' duration undergoing electrical cardioversion over a 6-month
      follow-up. METHODS: The ACUTE study was a multicenter, randomized, clinical
      trial, with 1222 patients. Six-month follow-up was available in 1034 patients
      (85%), 525 in the TEE group and 509 in the conventional group. The primary
      composite end points were cerebrovascular accident, transient ischemic attack,
      and peripheral embolism at 6 months, which was a prespecified time point.
      Secondary end points were hemorrhage, mortality, and sinus rhythm. RESULTS: At 6
      months, there was no difference in composite embolic events between the TEE group
      and the conventional group (10 [2%] vs 4 [0.8%]; risk ratio (RR) 2.47, 95% CI
      0.78-7.88; P = .11). However, the hemorrhagic rate was significantly lower in the
      TEE group (23 [4.4%] vs 38 [7.5%]; RR 0.58, 96% CI 0.35-0.97; P = .04). There was
      no difference between the 2 treatment groups in all-cause mortality (21 [4%] vs
      14 [2.8%]; RR 1.48, 95% CI 0.76-2.92; P = .25) and in the occurrence of normal
      sinus rhythm between the 2 groups (305 [62.2%] vs 280 [58.1%]; P = .51). Sinus
      rhythm at 6 months was more common in the TEE-guided group, in those patients who
      had direct current cardioversion (238 [62.5%] vs 151 [53.9%]; P = .03).
      CONCLUSION: The TEE-guided strategy may be considered a clinically effective
      alternative to a conventional anticoagulation strategy for patients with AF of >
      2 days' duration undergoing electrical cardioversion over a 6-month period.

PMID- 16442905
TI  - Prediction of the recurrence of atrial fibrillation after cardioversion in the
      Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.
AB  - BACKGROUND: The early recurrence of atrial fibrillation (AF) after cardioversion
      and the need for frequent cardioversions to maintain sinus rhythm are important
      clinical features of AF management. METHODS: We evaluated patients in the AFFIRM
      study whose qualifying episode of AF lasted > or = 48 hours and was terminated by
      cardioversion. Clinical, electrocardiographic, and echocardiographic risk factors
      associated with AF recurrence within 2 months of cardioversion and > or = 2
      cardioversions during the first year were identified using multivariate analysis
      in 1293 eligible patients. RESULTS: The risk factors for the recurrence of AF
      within 2 months of cardioversion were no coronary artery disease and an
      electrocardiographic lead II P-wave duration of > 135 milliseconds. In the subset
      of patients not taking antiarrhythmic drug therapy, the multivariate risk factors
      were no coronary artery disease, second or greater episode of AF, left
      ventricular ejection fraction < 0.50, and mitral valve thickening. Significant
      risk factors for the need for > 2 cardioversions in the first year in patients
      taking antiarrhythmic medication were left atrial diameter > 4.5 cm and mitral
      valve thickening. The overall sensitivity and specificity of these parameters for
      recurrence and repeated cardioversion are low. CONCLUSION: There are several risk
      factors for difficulty maintaining sinus rhythm after cardioversion of persistent
      AF. The clinical predictive value of these factors is low, and they probably
      should not be used to justify withholding rhythm control efforts in patients who
      might benefit from sinus rhythm.

PMID- 16442906
TI  - Predicting early mortality after implantable defibrillator implantation: a
      clinical risk score for optimal patient selection.
AB  - BACKGROUND: Patients with advanced heart disease are at risk from sudden death;
      however, benefit from implantable cardioverter defibrillators (ICDs) may be
      limited as a result of early mortality from other causes. The objective of this
      study was to develop a model to predict mortality within the first year after ICD
      implantation. METHODS AND RESULTS: A retrospective analysis was performed of 469
      consecutive patients who underwent ICD implantation at a single tertiary-care
      center from 1999 to 2002. Vital status was determined from the Social Security
      Death Index. Patients were randomized into prediction and validation cohorts. A
      risk score was derived from the prediction cohort by multivariate logistic
      regression and applied to the validation cohort. One point was assigned for each
      variable in the risk score (age > 80 years, history of atrial fibrillation,
      creatinine > 1.8 mg/dL, New York Heart Association class III or IV). One-year
      mortality significantly increased with increasing risk score in both the
      prediction and validation cohorts. Validation cohort mortality was 3.4% for 0
      points, 4.3% for 1 point, 17% for 2 points, and 33% for > or = 3 points (P for
      trend < .0001). A risk score > or = 2 predicted a 1-year mortality rate of 21%,
      whereas a risk score < 2 predicted a mortality rate of 4% at 1 year (P < .0001).
      CONCLUSION: A risk score using simple clinical criteria may identify patients at
      high risk of early mortality after ICD implantation. This may be helpful in
      consideration of ICD risk/benefit for individual patients. Further studies
      conducted in a prospective manner using these clinical criteria are warranted.

PMID- 16442907
TI  - Meta-analysis of comparative diagnostic performance of magnetic resonance imaging
      and multislice computed tomography for noninvasive coronary angiography.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) and multislice computed tomography
      (MSCT) have emerged as potential noninvasive coronary imaging techniques. The
      objective of the present study was to clarify the current accuracy of both
      modalities in the detection of significant coronary artery lesions (compared to
      conventional angiography as the gold standard) by means of a comprehensive meta
      analysis of the presently available literature. METHODS: A total of 51 studies on
      the detection of significant coronary artery stenoses (> or = 50% diameter
      stenosis) and comparing results with conventional angiography were identified by
      means of a MEDLINE search. Weighted sensitivities, specificities, and predictive
      values, all with 95% CIs, as well as summary odds ratios, were calculated for
      both techniques. In addition, the relationship between diagnostic specificity and
      disease prevalence was determined using metaregression analysis. RESULTS: A
      comparison of sensitivities and specificities revealed significantly higher
      values for MSCT (weighted average 85% [95% CI 86%-88%] and 95% [95% CI 95%]) as
      compared with MRI (weighted average 72%, 95% CI 69%-75% and 87%, 95% CI 86%-88%).
      A significantly higher odds ratio (16.9-fold) for the presence of significant
      stenosis was observed for MSCT as compared with MRI (6.4-fold) (P < .0001).
      Linear regression analysis revealed a better specificity for MSCT versus MRI in
      lower disease prevalence populations (P = .056). CONCLUSION: Meta-analysis of the
      available studies with MRI and MSCT for noninvasive coronary angiography
      indicates that MSCT has currently a significantly higher accuracy to detect or
      exclude significant coronary artery disease.

PMID- 16442908
TI  - Left atrial diameter as an independent predictor of first clinical cardiovascular
      events in middle-aged and elderly adults: the Strong Heart Study (SHS).
AB  - BACKGROUND: Echocardiographic left atrial (LA) volume has been documented to be
      an independent predictor of cardiovascular events. Less is known about the
      predictive ability of anteroposterior LA diameter, a simpler measure of LA size
      obtained routinely during echocardiographic evaluation. METHODS: We investigated
      the prognostic value of LA diameter for incident cardiovascular events in 2804
      American Indians free of clinical cardiovascular disease, valvular disease, and
      atrial fibrillation. Echocardiographic variables were obtained using standardized
      methods, and previously derived sex-specific partition values were used to define
      left ventricular (LV) hypertrophy indexed to height(2.7) (in meters) and LA
      enlargement (> 4.2 cm in men, > 3.8 cm in women). Cardiovascular events included
      nonfatal stroke, coronary heart disease, congestive heart failure, and fatal
      cardiovascular disease based on validated definitions. RESULTS: During a median
      follow-up of 7 years, 368 events occurred. LA diameter, both as a continuous and
      as a categorical variable, was significantly associated with incident
      cardiovascular events in unadjusted analyses. In multivariable analyses that
      adjusted for age, sex, body mass index, hypertension, diabetes, total cholesterol
      high-density lipoprotein cholesterol, smoking, renal insufficiency, LV
      hypertrophy, abnormal LV systolic and diastolic function, mitral annular
      calcification, fibrinogen, and C-reactive protein, both LA diameter (risk ratio
      1.04/mm, 95% CI 1.02-1.07, P < .002) and LA enlargement (risk ratio 1.57, 95% CI
      1.17-2.10, P = .002) remained independent predictors of first cardiovascular
      events. CONCLUSIONS: In this population-based cohort, LA diameter independently
      predicted incident cardiovascular events after adjustment for established
      clinical, echocardiographic, and inflammatory risk factors. This simple measure
      of LA dilatation can identify individuals at heightened risk who may warrant more
      aggressive risk factor modification.

PMID- 16442909
TI  - Wall motion score index and ejection fraction for risk stratification after acute
      myocardial infarction.
AB  - BACKGROUND: The prognostic importance of regional systolic function, as assessed
      by wall motion score index (WMSI), compared with global function, as assessed by
      left ventricular ejection fraction (LVEF), has not been assessed in large
      populations after acute myocardial infarction. METHODS: Echocardiograms,
      including the assessment of WMSI and LVEF, were performed in 767 patients with
      acute myocardial infarction at a median of 1 day (25th and 75th percentiles 0-2
      days) after admission. Patients were followed for a median of 19 months (range 12
      28 months). Cox proportional hazards models were constructed for the primary
      study end point (all-cause mortality) and for a secondary end point
      (hospitalization for congestive heart failure). RESULTS: During follow-up (median
      40 months; range 32-50 months), 216 patients died and 54 patients were
      hospitalized for congestive heart failure. By univariate analysis, both LVEF (P <
      .0001) and WMSI (P < .0001) were powerful predictors of all-cause mortality. By a
      forward conditional Cox model, WMSI proved to be an independent predictor of
      death (hazard ratio 1.15 per 0.2-unit increase, 95% CI 1.10-1.21, P < .0001).
      When WMSI was included in the model, LVEF did not provide additional prognostic
      information (P = .77). Wall motion score index also proved to be an independent
      predictor of hospitalization for congestive heart failure (hazard ratio 1.21 per
      0.2-unit increase, 95% CI 1.07-1.37, P = .002), whereas LVEF did not (P = .56).
      CONCLUSION: Both LVEF and WMSI provide powerful prognostic information after
      acute myocardial infarction; however, the predictive power of WMSI is greater.

PMID- 16442910
TI  - Prognostic utility of single-photon emission computed tomography in adult
      patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Data derived from stress myocardial perfusion imaging (MPI) carry
      prognostic significance in young patients with hypertrophic cardiomyopathy (HCM),
      but there are limited data on the utility of stress MPI in patients with HCM who
      are older. This study examined the prognostic significance of stress MPI in an
      adult population of patients with HCM. METHODS: We examined 158 patients with HCM
      (aged 60 +/- 16 years, 61% men) who underwent exercise or pharmacologic stress
      MPI. Summed stress score (SSS, normal = 56) and summed reversibility scores were
      calculated for each patient. Follow-up was complete in 157 (99%) patients at a
      median duration of 5.2 years. RESULTS: Normal single-photon emission computed
      tomography (SPECT) images were present in 38% of the population. Summed stress
      score (P = .01) and summed reversibility score (P = .03) were both significantly
      associated with cardiovascular death. Survival at 10 years was significantly
      better in those with normal versus abnormal SPECT (89% vs 67%, P = .04). Ten-year
      survival also was better in those without versus those with ischemia (90% vs 64%,
      P = .02). Five-year survival could be stratified by SSS risk categories: low risk
      (SSS > or = 53), 97%; intermediate risk (SSS = 48-52), 94%; and high risk (SSS <
      or = 47), 79% (P = .04). Bivariate models of SSS and other significant covariates
      supported an independent relation of SSS to cardiovascular death. CONCLUSIONS: In
      an older population of patients with HCM referred for SPECT imaging, abnormal
      stress MPI identifies those at increased risk of cardiovascular death.

PMID- 16442911
TI  - Cardiac pacemaker: in vitro assessment at 1.5 T.
AB  - BACKGROUND: In vitro testing is used to determine safe parameters before
      performing magnetic resonance imaging (MRI) on a patient with an implant.
      Therefore, the objective of this study was to evaluate a cardiac pacemaker using
      a 1.5-T magnetic resonance (MR) system. METHODS: A modern cardiac pacemaker
      (INSIGNIA I PLUS, Model 1298, and FINELINE II, Model 4471, pacing leads; Guidant
      Corporation, St Paul, MN) was evaluated for magnetic field interactions at 1.5 T.
      Magnetic resonance imaging-related heating was assessed using 3 different 1.5-T
      scanners operating at various levels of radio-frequency power and imaging
      conditions. Functional aspects of the pacemaker were evaluated immediately before
      and after MRI (9 different pulse sequences). Artifacts were also characterized.
      RESULTS: Magnetic field interactions for the pacemaker were minor. Temperature
      changes measured in vitro were at levels that are not expected to pose a risk for
      specific MR conditions (< 4.0 degrees C). The function of the pacemaker was
      unaffected by MRI. Artifacts were minor for the leads and relatively large for
      the implantable pulse generator. CONCLUSION: The findings indicated that this
      pacemaker exhibited acceptable safety features relative to the use of a 1.5-T MR
      system. If induced currents do not occur for this device, it may be safe for a
      patient to undergo MRI by following specific conditions. The results are specific
      to the pacemaker tested, the MR systems, and conditions used in this evaluation.

PMID- 16442912
TI  - Higher New York Heart Association classes and increased mortality and
      hospitalization in patients with heart failure and preserved left ventricular
      function.
AB  - BACKGROUND: The association between higher New York Heart Association (NYHA)
      class and outcomes in patients with heart failure and preserved systolic function
      is not well known. METHODS: We performed a retrospective follow-up study of 988
      patients with heart failure with ejection fraction > 45% who participated in the
      DIG trial. Using Cox proportional hazard models, we estimated risks and all-cause
      mortality, heart failure mortality, all-cause hospitalization, and
      hospitalization due to worsening heart failure during a median follow-up of 38.5
      months. RESULTS: Patients had a median age of 68 years; 41.2% were women and
      13.9%, nonwhites. Overall, 23.4% of patients died, and 19.9% were hospitalized
      because of worsening heart failure. Proportion of patients with NYHA classes I,
      II, III, and IV were 19.9%, 58.0%, 20.9%, and 1.2%, respectively, and 14.7%,
      21.1%, 35.9%, and 58.3%, respectively, died of all causes (P < .001 for trend).
      Respective rates for heart failure-related hospitalizations were 14.2%, 17.1%,
      32.5%, and 33.3% (P < .001 for trend). Compared with NYHA class I patients,
      adjusted hazard ratios (HRs) for all-cause mortality for class II, III, and IV
      patients were 1.54 (95% CI 1.02-2.32, P = .042), 2.56 (95% CI 1.64-24.01, P <
      .001), and 8.46 (95% CI 3.57-20.03, P < .001), respectively. Respective adjusted
      HRs (95% CI) for hospitalization due to heart failure for class II, III, and IV
      patients were 1.16 (0.76-1.77) (P = .502), 2.27 (1.45-3.56) (P < .001), and 3.71
      (1.25-11.02) (P = 018). New York Heart Association classes II through IV were
      also associated with higher risk of all-cause hospitalization. CONCLUSION: Higher
      NYHA classes were associated with poorer outcomes in patients with heart failure
      and preserved systolic function.

PMID- 16442913
TI  - A cooperative network of trained sites for the conduct of a complex clinical
      trial: a new concept in multicenter clinical research.
AB  - BACKGROUND: The purpose of this report is to present a model of physicians in
      full-time clinical practice participating as investigators in multicenter
      clinical trials, sponsored by a pharmaceutical or medical device company.
      METHODS: This gas-exchange substudy was conducted as a pilot study to establish
      the feasibility of the 10-member EXERcise testing group of the Duke University
      Cooperative Cardiovascular Society (EXERDUCCS) consortium to perform a complex
      multicenter trial using cardiopulmonary exercise testing. An active interchange
      of information was established involving the principal investigator for the
      substudy, a dedicated full-time project coordinator, a medical director of the
      overall EXERDUCCS network site, the project coordinator for the sponsor, and all
      the participating EXERDUCCS investigators and coordinators. RESULTS: The sponsor
      set as a goal of enrollment of 6 subjects per site, and 8 of the 10 sites met
      this goal. As a result of the successful enrollment and completion of the study
      and substudy by the EXERDUCCS sites, the sponsor subsequently increased the
      payment stipends to the sites to compensate for the extra work and expense
      incurred. CONCLUSIONS: This cooperative experience accomplished several goals:
      (1) it allowed a complex clinical trial to be successfully completed in a time
      frame which would not have been possible using only single unconnected sites; (2)
      it educated the physician-investigators (and their personnel) in exercise
      cardiopulmonary; and (3) it prepared the sites for future clinical trials
      involving this methodology.

PMID- 16442915
TI  - Survival in biopsy-proven myocarditis: a long-term retrospective analysis of the
      histopathologic, clinical, and hemodynamic predictors.
AB  - OBJECTIVE: We hypothesized that histopathology predicts survival without cardiac
      transplantation in patients with biopsy-proven myocarditis. BACKGROUND: The role
      of endomyocardial biopsy in diagnosing myocarditis remains controversial.
      Histopathology has been integrated with clinical and hemodynamic features to
      predict prognosis. However, the influence of histopathology on survival > 5 years
      has not been explored. METHODS: We retrospectively identified 112 consecutive
      patients with histopathologic confirmation of myocarditis. We examined these
      patients' clinical presentation, hemodynamic assessment, hospital course, and
      treatment. We selected 14 variables that might influence survival without cardiac
      transplantation. RESULTS: A total of 62 (55%) of 112 patients had lymphocytic
      myocarditis; 88 (79%) and 63 (56%) were alive without cardiac transplantation at
      1 and 5 years, respectively. Median follow-up was a mean 95.5 months and median
      74.5 months. Among the 55 with complete data of the 14 candidate predictor
      variables, age, sex, and clinical presentation with congestive heart failure and
      ventricular (ventricular tachycardia or fibrillation) or atrial arrhythmias
      (atrial fibrillation or flutter) did not predict the study end point of death or
      need for transplantation. In univariate analysis, pulmonary capillary wedge
      pressure > or = 15 mm Hg significantly predicted the study end point. In
      multivariate analysis, pulmonary capillary wedge pressure > or = 15 mm Hg and
      histopathology of lymphocytic, granulomatous, or giant cell myocarditis each
      significantly predicted mortality or transplant (P = .047, P = .013, and P =
      .054, respectively) on cumulative survival without cardiac transplantation.
      CONCLUSIONS: Histopathology predicts long-term survival in patients with
      myocarditis. Clinical presentation, including presentation with congestive heart
      failure, ventricular tachycardia/ventricular fibrillation, or atrial
      fibrillation/atrial flutter, does not predict survival without transplantation.
      Endomyocardial biopsy can play a role in predicting transplant-free survival in
      patients with myocarditis.

PMID- 16442914
TI  - Anemia in patients with heart failure and preserved systolic function.
AB  - BACKGROUND: Anemia has been shown to be a predictor of mortality in patients with
      heart failure and impaired left ventricular systolic function (ISF). Although
      heart failure in the setting of preserved systolic function (PSF) is an important
      clinical problem, the relationship between anemia and outcomes in patients with
      PSF has not been carefully evaluated. METHODS: Patients undergoing diagnostic
      angiography from 1995 to 2003 with symptomatic heart failure (New York Heart
      Association class II or greater) were studied (N = 4951). Patients with primary
      valvular or congenital heart disease were excluded. Patients with ejection
      fraction < or = 0.40 (N = 1858) were considered the ISF group, and patients with
      ejection fraction > 0.40 (N = 3093) were classified as the PSF group. Anemia was
      defined by the World Health Organization criteria (hemoglobin < 13 g/dL for men
      and < 12 g/dL for women). Multivariable Cox proportional hazards models were used
      to adjust for baseline differences. The possibility of a differential effect of
      anemia by systolic function was tested using an interaction term in the
      multivariable model. RESULTS: Anemia was independently associated with adverse
      outcomes across the study cohort (adjusted hazard ratio = 1.53, P < .0001). There
      was no interaction between anemia and systolic function (ISF vs PSF) in the
      multivariable model (P = .31 for interaction). The hazard ratio for anemia was
      1.61 for PSF patients and 1.45 for ISF patients. CONCLUSIONS: Anemia is an
      independent predictor of mortality in heart failure, regardless of whether
      patients have preserved or impaired systolic function. This is the first report
      of an association between anemia and increased mortality in patients with heart
      failure and PSF. Future investigations of therapies for anemia in heart failure
      should consider including patients with PSF.

PMID- 16442916
TI  - Use of B-type natriuretic peptide in the management of acute dyspnea in patients
      with pulmonary disease.
AB  - BACKGROUND: In patients with pulmonary disease, it is often challenging to
      distinguish exacerbated pulmonary disease from congestive heart failure (CHF).
      The impact of B-type natriuretic peptide (BNP) measurements on the management of
      patients with pulmonary disease and acute dyspnea remains to be defined. METHODS:
      This study evaluated the subgroup of 226 patients with a history of pulmonary
      disease included in the BASEL Study. Patients were randomly assigned to a
      diagnostic strategy with (n = 119, BNP group) or without (n = 107, clinical
      group) the use of BNP levels provided by a rapid bedside assay. Time to discharge
      and total cost of treatment were recorded as the primary end points. RESULTS:
      Baseline characteristics were similar in patients assigned to the BNP and control
      groups. Comorbidity was extensive, including coronary artery disease and
      hypertension in half of patients. The primary discharge diagnosis was CHF and
      exacerbated obstructive pulmonary disease in 39% and 33%, respectively. The use
      of BNP levels significantly reduced the need for hospital admission (81% vs 91%,
      P = .034). Median time to discharge was 9.0 days in the BNP group as compared
      with 12.0 days (P = .001) in the clinical group. Median total cost of treatment
      was $4841 in the BNP group as compared with $5671 in the clinical group (P =
      .008). Inhospital mortality was 8% in both groups. CONCLUSIONS: CHF is a major
      cause of acute dyspnea in patients with a history of pulmonary disease. Used in
      conjunction with other clinical information, rapid measurement of BNP reduced
      time to discharge and total treatment cost of these patients.

PMID- 16442917
TI  - Clinical predictors of marked improvement in left ventricular performance after
      cardiac resynchronization therapy in patients with chronic heart failure.
AB  - BACKGROUND: Previous studies have shown that cardiac resynchronization therapy
      (CRT) improves cardiac performance and decreases mortality and hospital admission
      rates. However, it is not yet clear which patients will benefit from the
      procedure the most. The purpose of the study was to identify the pre-implant
      characteristics that better predict which patients will have the best outcome
      after CRT. METHODS: In this observational study, 156 patients were studied with
      echocardiography and a 6-minute walking test at baseline and 12 months after CRT.
      RESULTS: After CRT, we observed an increase in left ventricular ejection fraction
      (+29.6%, P < .0001), a decrease in left ventricular end systolic volume (-26.4%,
      P < .0001), in the proportion of patients with grade 2-4 mitral regurgitation
      (from 47.1% to 34.0%, P = .002), and with NYHA functional class III-IV (from
      83.2% to 11.6%, P < .0001), an increase in exercise tolerance (+31.1%, P <
      .0001). Sixty-two patients had a marked increase in left ventricular ejection
      fraction (> 10 units); the only independent predictor of a marked effect of CRT
      was the nonischemic etiology of heart failure. In patients with ischemic
      cardiomyopathy, the benefit on ejection fraction correlates inversely with the
      extension of the ischemic damage. CONCLUSIONS: CRT improves left ventricular
      function and exercise tolerance in the long term. The nonischemic etiology of the
      cardiomyopathy is the only independent predictor of a marked effect of CRT; this
      is probably due to the absence of ischemic, nonviable scar tissue in these
      patients.

PMID- 16442918
TI  - Mortality benefit of a comprehensive heart failure disease management program in
      indigent patients.
AB  - BACKGROUND: Heart failure (HF) produces significant morbidity and mortality.
      Although HF disease management (HFDM) programs have been shown to decrease this
      morbidity, there is still a paucity of data on their effect on mortality. The
      objective of this study was to determine whether participation in an HFDM program
      would reduce mortality in an indigent population from rural Louisiana. METHODS:
      Proportional hazards modeling was used to determine whether patients
      participating in the HFDM program had improved survival compared with patients
      receiving traditional outpatient care at the same institution. Inclusion criteria
      consisted of an index hospitalization with discharge occurring between July 1,
      1997, and May 30, 2002, hospital discharge diagnosis of HF, left ventricular
      systolic dysfunction documented during hospitalization, and at least 1 subsequent
      outpatient visit. Data from patients having participated in the HFDM program
      before their index hospitalization were excluded. RESULTS: Compared with patients
      who were given traditional care (n = 100), HFDM patients (n = 156) were younger
      (56.7 vs 60 years, P = .031), more likely to be African American (48.7% vs 33.0%,
      P = .014), more likely to be uninsured (47.4% vs 27%, P = .001), and more likely
      to have an ejection fraction of < or = 25% (73.1% vs 36%, P < .001). Overall
      comorbidity did not differ significantly between the groups. After controlling
      for differences in demographics, ejection fraction, and comorbidities,
      participation in the HFDM program was associated with a significant reduction in
      mortality compared with traditional care (adjusted hazard ratio .33, P < .001).
      CONCLUSION: In this indigent population, participation in an HFDM program was
      associated with decreased mortality compared with traditional follow-up care.

PMID- 16442919
TI  - The role of exercise in modulating the impact of an ultralow-fat diet on serum
      lipids and apolipoproteins in patients with or at risk for coronary artery
      disease.
AB  - BACKGROUND: Ultralow-fat diets are known to reduce high-density lipoprotein
      cholesterol (HDL-C) levels. In the setting of a multicomponent lifestyle
      intervention program, relationships between exercise variables and HDL-C levels
      were examined to determine whether exercise moderates this dietary effect on
      serum lipids and apolipoproteins. METHODS: We performed a 3-month, prospective,
      nonrandomized lifestyle intervention study (< or = 10% dietary fat; aerobic
      exercise [180 min/wk], group support, and yoga [60 min/day]) in 120 subjects with
      or at risk for coronary artery disease. RESULTS: After 3 months, dietary fat
      intake was reduced to 8.7% +/- 2.6% of total intake and the median weekly
      exercise time was 194 minutes. High-density lipoprotein cholesterol levels
      decreased by 8.3 +/- 11.3 mg/dL (P < .001), and triglyceride levels increased by
      17.6 +/- 102.7 mg/dL (P = .026). A small dense low-density lipoprotein
      cholesterol (LDL-C) phenotype emerged indicated by a 13.8% LDL-C reduction
      accompanied by only a 2.3% reduction in apolipoprotein B levels (P = .064). Among
      subjects with exercise amounts less than those of the group median, HDL-C
      reductions were greater in those with more than (-13.5 +/- 16.0 mg/dL) versus
      less than (-2.5 +/- 7.5 mg/dL) the median reductions in fat intake (P = .026).
      Even among subjects who exercised > 194 min/wk, HDL-C was reduced compared with
      baseline (-7.4 +/- 7.9 mg/dL, P < .001). CONCLUSIONS: An ultralow-fat diet as a
      component of a comprehensive lifestyle intervention induces reductions in HDL-C
      and the emergence of a dyslipidemic lipid profile. Aerobic exercise only
      partially mitigates this effect.

PMID- 16442920
TI  - Kidney function and anemia as risk factors for coronary heart disease and
      mortality: the Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Kidney failure causes anemia and is associated with a very high risk
      of coronary heart disease (CHD). Mildly to moderately decreased kidney function
      is far more common and also is associated with an elevated prevalence of anemia
      and CHD risk. Recent data suggest an even higher risk of CHD when both conditions
      are present. METHODS: We investigated the association of kidney dysfunction and
      anemia with CHD events (fatal or nonfatal CHD or coronary revascularization
      procedures) and CHD and all-cause mortality over 12 years of follow-up in 14971
      adults aged 45 to 64 years in the ARIC Study. Glomerular filtration rate (GFR)
      was estimated from calibrated serum creatinine using the MDRD Study equation (<
      30 mL/min per 1.73 m2 excluded, n = 32). Anemia was defined as hemoglobin level <
      13.5 g/dL in men (648/6746, 9.6%) and < 12 g/dL in women (1049/8225, 12.8%).
      RESULTS: The prevalence of anemia was progressively higher at lower estimated GFR
      < 75 mL/min per 1.73 m2 (both P < .001) for both men and women. A total of 1635
      (10.9%) participants had a CHD event, 360 (2.4%) died of CHD, and 1722 (11.5%)
      died of any cause during follow-up. After adjustment for known risk factors,
      including diabetes, lipid levels, blood pressure, and use of antihypertensive
      medication, decreased kidney function was associated with a higher risk of
      recurrent CHD events and mortality from CHD and all causes. These associations
      were significantly stronger among participants with anemia. The adjusted relative
      hazards of all-cause mortality associated with moderately decreased versus normal
      kidney function (GFR 30-59 vs > or = 90 mL/min per 1.73 m2) were 1.7 (95% CI 1.3
      2.2) in the absence of anemia and 3.5 (95% CI 2.4-5.1) in the presence of anemia
      (P interaction = .001). CONCLUSIONS: The combination of moderately decreased
      kidney function and anemia is associated with an increased risk of CHD events and
      mortality, emphasizing the need to identify individuals with these conditions and
      evaluate interventions to treat anemia and slow the progression of chronic kidney
      disease.

PMID- 16442921
TI  - Trends in community mortality due to coronary heart disease.
AB  - BACKGROUND: Relatively little data are available, particularly from the more
      generalizable perspective of a population-based investigation, describing recent
      trends in death rates due to coronary heart disease (CHD). The objectives of this
      observational study were to describe changes over a twelve year period (1990
      2001) in death rates due to CHD and acute myocardial infarction (AMI) in
      residents of the Worcester, Massachusetts, metropolitan area (2000 census =
      478,000). A secondary study goal was to describe changes in death rates
      attributed to CHD over time separately in men and in women, in persons of
      different ages, and according to location of death. METHODS: Death datatapes were
      obtained from the Massachusetts Department of Public Health for greater Worcester
      residents who died over the period 1990 to 2001. RESULTS: Marked declines were
      observed in the population death rates (per 100,000) due to CHD (1990 death rate
      = 322; 2001 death rate = 224) and AMI (1990 death rate = 137; 2001 death rate =
      87) in the greater Worcester population. Declines in the annual death rates
      attributed to CHD were observed in both the hospital (4.4% decline) and out-of
      hospital setting (1.6% decline) as well as for patients dying from AMI (annual
      declines of 4.8% and 1.9% respectively). Reductions in CHD death rates over time
      were observed in men and in women and in persons of all ages. CONCLUSIONS: The
      present results demonstrate encouraging declines in community death rates due to
      CHD and AMI over time and the impact of evolving primary and secondary prevention
      efforts.

PMID- 16442922
TI  - Long-term prognostic value of the preoperative 12-lead electrocardiogram before
      major noncardiac surgery in coronary artery disease.
AB  - BACKGROUND: Knowledge of the prognostic information of preoperative 12-lead
      electrocardiogram (ECG) recordings in patients with coronary artery disease (CAD)
      undergoing noncardiac surgery is limited. METHODS: The prognostic information
      derived from the preoperative ECGs of 172 CAD patients undergoing major
      noncardiac surgery was analyzed to determine its predictive value for long-term
      outcome. Primary end point was all-cause mortality; secondary end point was major
      adverse cardiac events (MACE) at 2 years. RESULTS: Prevalence of ECG
      abnormalities was 53% for T-wave alterations; 46% for Q waves; 38% for ST
      deviations; and, depending on the criterion used, 2% to 19% for left ventricular
      hypertrophy. During follow-up, 40 (23%) patients died and 31 (18%) had MACE.
      After adjustment for clinical baseline findings, including current medication
      with beta-blockers, ST depressions (odds ratio [OR] 4.5, 95% confidence interval
      [CI] 1.9-10.5) and faster heart rate (HR) (OR 1.6, 95% CI 1.1-2.4, per 10 beats
      per minute [bpm] increase) were independent predictors of all-cause mortality.
      Faster HR (OR 1.7, 95% CI 1.1-2.6, per 10-bpm increase) was also an independent
      predictor of MACE. The predictive value of ECG variables did not change after
      adjustment for occurence of perioperative ischemia. CONCLUSION: In CAD patients,
      the preoperative ECG contains important prognostic information and is predictive
      of long-term outcome independent of clinical findings and perioperative ischemia.

PMID- 16442923
TI  - The metabolic syndrome and its components and the long-term risk of death in
      patients with coronary heart disease.
AB  - BACKGROUND: The metabolic syndrome confers an increased risk of major
      cardiovascular events in individuals initially free from coronary heart disease
      (CHD). Presently, approximately 25% of the US population possesses the metabolic
      syndrome as defined using the National Cholesterol Education Program (NCEP)
      criteria. We sought to assess the impact of the metabolic syndrome and its
      individual components on intermediate-term and long-term outcomes in patients
      with CHD. METHODS: The CASS registry represents a database of 24,958 patients
      with suspected or proven CHD who underwent cardiac catheterization between 1974
      and 1979. Mean long-term follow-up was 12.6 +/- 5.1 years. Metabolic syndrome was
      defined using modified definitions of the NCEP and World Health Organization
      (WHO) because high-density lipoprotein cholesterol measures were not available.
      RESULTS: We identified 3279 and 1080 patients with metabolic syndrome using our
      modified NCEP and WHO definitions, respectively. Adjusted long-term all-cause
      death was higher in patients with metabolic syndrome (hazard ratio [HR] 1.21, 95%
      CI 1.14-1.29; HR 1.56, 95% CI 1.43-1.70 for NCEP and WHO criteria, respectively).
      Similarly, long-term adjusted risk of cardiovascular death and intermediate-term
      risk of morbidity and mortality were higher in patients with the metabolic
      syndrome. Fasting blood glucose > or = 110 mg/dL was responsible for most of the
      increased risk associated with the metabolic syndrome (adjusted HR 1.47, 95% CI
      1.39-1.56). CONCLUSIONS: The metabolic syndrome confers a higher risk of long
      term death in patients with preexisting CHD, and dysglycemia appears to be
      responsible for most of the associated risk.

PMID- 16442924
TI  - Effects of clopidogrel on soluble CD40 ligand and on high-sensitivity C-reactive
      protein in patients with stable coronary artery disease.
AB  - BACKGROUND: Antiplatelet therapy with clopidogrel decreases ischemic complication
      especially in patients with acute coronary syndromes or after percutaneous
      coronary interventions. Our study was designed to test the effects of clopidogrel
      on soluble CD40 ligand (sCD40l) and on high-sensitivity C-reactive protein (hs
      CRP) in patients with stable coronary artery disease (CAD). METHODS: This is a
      randomized, double-blind, placebo-controlled study. A total of 73 patients with
      stable CAD for > 6 months were randomized to receive either clopidogrel (loading
      dose 300 mg followed by 75 mg/d) for 8 weeks or placebo. Soluble CD40 ligand and
      hs-CRP were measured at baseline and at completion of the study. RESULTS: All
      patients were on aspirin therapy, and 74% were on statins. Median and
      interquartile ranges (IQR) of sCD40l decreased from 64 pg/mL (43-99) at baseline
      to 53 pg/mL (35-77) at 8 weeks (P = .03) in the clopidogrel group and remained
      unchanged in the placebo group (59 pg/mL, IQR 35-77 vs 55 pg/mL, IQR 35-78) (P =
      non significant). Levels of hs-CRP were not affected by therapy and remained
      unchanged in both groups. CONCLUSIONS: In patients with stable CAD, clopidogrel
      inhibits the release of sCD40l by platelets, which may contribute to the clinical
      benefit provided by this drug. This, however, does not translate in a reduction
      of subclinical inflammation, as measured by hs-CRP.

PMID- 16442925
TI  - Psychophysiologic responses of invasive cardiologists in an academic
      catheterization laboratory.
AB  - BACKGROUND: This study examined the psychophysiologic responses of invasive
      cardiologists during cardiac catheterizations. Because occupations are most
      stressful when one is not in control, the effect of a teaching versus an
      autonomous role on the psychophysiologic response of invasive cardiologists was
      investigated. METHODS: The subjects were 9 invasive cardiologists.
      Psychophysiologic variables such as state anxiety and salivary cortisol levels
      were measured before and after each invasive cardiologist performed 7 cardiac
      catheterizations. Heart rate was measured before, during, and after procedures.
      Three procedures were studied while invasive cardiologists were in the primary
      operator (autonomous) role with full responsibility and control, whereas 4 were
      studied while the subjects were in the secondary assistant (teaching) role with
      full responsibility and no control. RESULTS: There were no significant
      differences in physiologic arousal (heart rate and salivary cortisol levels)
      between catheterizations performed in the autonomous role versus those in the
      teaching role. However, the perceived anxiety scores were higher when in the
      teaching role versus when in the autonomous role. There were significant
      differences in psychophysiologic measurements of stress between less experienced
      cardiologists (out of training < 5 years) and more experienced cardiologists (out
      of training > 5 years). Less experienced invasive cardiologists had significantly
      higher trait anxiety (38.4 vs 31.7, P = .001), baseline salivary cortisol levels
      (0.51 vs 0.33, P = .01), and heart rate change (50.1 vs 27.4 beats/min, P = .001)
      during procedures compared with more experienced cardiologists. CONCLUSIONS:
      Although there were no overall differences in the physiologic response to the
      autonomous and teaching roles, there was a higher perceived state of anxiety when
      in the teaching role. Less experienced invasive cardiologists had higher
      psychophysiologic measurements of stress during invasive procedures than did more
      experienced cardiologists.

PMID- 16442926
TI  - Effect of percutaneous coronary intervention of nonacute total coronary artery
      occlusions on QT dispersion.
AB  - BACKGROUND: Myocardial ischemia is one of several potential causes of increased
      QT dispersion (QTd) in patients with nonacute total coronary artery occlusions
      (TCOs). We sought to assess the effect of percutaneous revascularization (PCI) of
      TCO on QTd and the relationship between QTd and long-term vessel patency.
      METHODS: Seventy patients enrolled in the TOSCA were analyzed. Patients were
      undergoing PCI of a TCO > 72 hours' duration. Two independent reviewers measured
      QTd from electrocardiograms done immediately before PCI (PRE), 12 to 18 hours
      after PCI (POST), and then at 6 months (6M). Follow-up angiography was performed
      at 6 months. RESULTS: Mean QTd decreased from PRE (77 +/- 29 milliseconds) to
      POST (66 +/- 26 milliseconds, P < .001) and 6M (65 +/- 25 milliseconds, P <
      .001). Patients with the same or longer QTd at 6 months compared with POST (POST
      < or = 6M) had significantly higher risk of failed target-vessel patency (odds
      ratio 10.3, 95% CI 1.24-84.8) than patients with QTd reduction at 6M versus POST
      values. CONCLUSION: Revascularization of TCO resulted in a decrease in QTd, which
      was sustained at 6M. This suggests that PCI to a TCO has a beneficial effect on
      stabilization of the underlying ischemic substrate. Furthermore, absence of QTd
      reduction at 6M versus POST was associated with increased risk of failed target
      vessel patency.

PMID- 16442927
TI  - Endovascular stent-graft treatment of penetrating aortic ulcer: results over a
      median follow-up of 27 months.
AB  - BACKGROUND: Penetrating aortic ulcer (PAU) is increasingly acknowledged as a
      pathological variant of classic false-lumen aortic dissection with a high
      incidence of bleeding complications and rupture in up to 40% of patients. The
      objective of this study was to investigate the results of endovascular stent
      graft placement for the treatment of patients with PAUs. METHODS: Between July
      1999 and December 2004, endovascular stent-graft repair of PAU was performed in
      22 patients (69.1 +/- 7.8 years, 16 men), 3 (14%) of whom had contained aortic
      rupture. Stent-graft placement was performed in the cardiac catheterization
      laboratory with the patient under general anesthesia, using a surgical access.
      RESULTS: Procedural success was achieved in all but 1 patient (technical success
      rate 96%). Postoperatively, 1 (5%) patient had minor stroke with transient
      amentia. There were no other inhospital complications or deaths. During a median
      follow-up of 27 (range 1-62) months, 1 patient underwent adjunctive stent-graft
      placement for type I endoleak. Three patients died unrelated to the aortic
      disease late during follow-up. Overall survival rates were 100% at 30 days, 100%
      at 1 year, 82.5% +/- 11.3% at 2 years, and 61.9% +/- 20.0% at 5 years.
      CONCLUSIONS: Endovascular stent-graft treatment is an effective treatment for
      patients with PAU and is associated with low procedural morbidity. Both acute and
      midterm mortality of this novel treatment concept appear to be favorable compared
      with the natural course of the disease.

PMID- 16442928
TI  - Asymptomatic long-term survivors of coronary artery bypass surgery enjoy a
      quality of life equal to the general population.
AB  - BACKGROUND: Health-related quality of life (HRQOL) among long-term survivors of
      coronary artery bypass surgery is an important outcome that has been little
      studied at the population level. METHODS: A postal survey was conducted in 1999
      to 2000 in patients 6 to 20 years after coronary artery bypass graft (CABG)
      surgery in Western Australia. A random stratified sample of 2500 was drawn from
      8910 patients who had their first CABG surgery in 1980 to 1993. Health-related
      quality of life was measured with Short Form 36 and EuroQol visual analogue
      scale. RESULTS: Response was 82% (n = 2061). Health-related quality of life
      declined with age and was similar for men and women, although scores for women
      were worse for physical functioning. Compared with Australian population norms,
      the age- and sex-standardized scores of survivors of CABG were generally worse,
      mainly in the physical domain. Reported angina at the time of follow-up (33%),
      symptoms of heart failure equivalent to New York Heart Association (NYHA) classes
      II to IV (34%), and comorbidities such as diabetes and hypertension were
      associated with poorer HRQOL. For both men and women without angina or heart
      failure at follow-up, HRQOL was no different from that of the general population.
      CONCLUSION: Overall, the quality of life among long-term survivors of CABG is
      worse than that of the general population, the difference being mainly
      attributable to recurrent symptoms and comorbidities. Quality of life for those
      without angina or heart failure at follow-up was equivalent to the population
      norms, providing an incentive to maximize efforts to abolish angina and
      ameliorate heart failure symptoms.

PMID- 16442929
TI  - Epidemiologic, clinical, and microbiologic profile of infective endocarditis in
      Argentina: a national survey. The Endocarditis Infecciosa en la Republica
      Argentina-2 (EIRA-2) Study.
AB  - BACKGROUND: This study aimed to determine the epidemiologic, clinical,
      microbiologic characteristics, and inhospital outcome of infective endocarditis
      (IE) in Argentina and compare the results with those of the 1992 IE national
      survey. METHODS: A prospective, multicenter study was conducted in 82 hospitals
      representing 16 of 24 provinces of Argentina. Patients with diagnosis of IE
      according to the Duke criteria were surveyed during an 18-month period. RESULTS:
      From 470 surveyed episodes of IE, 390 cases were classified as definite and 80 as
      possible IE. The mean age of the definite IE cases was 58.5 +/- 17.3 years; male
      sex, 70.0%; and male-female ratio, 2.3:1. Pathological evidence of IE was
      available in 26.2%. There was no previously known heart disease in 35.1%, and the
      proportion of prosthetic valve IE was 15.9%. Causative microorganisms were
      streptococci, 38.3% (Streptococcus viridans 27.0%, Streptococcus bovis 5.2%,
      others 6.1%); enterococci, 10.2%; staphylococci, 36.7% (Staphylococcus aureus
      29.8%, coagulase-negative staphylococci 6.9%); HACEK group, 6.1%; fungal, 1.4%;
      and polymicrobial, 2.0%. Blood culture results were negative in 10.8%. Surgical
      treatment was performed in 26.2%, and the overall inhospital mortality was 24.6%.
      Patients from the 2002 survey were older (58.5 +/- 17.3 vs 51.3 +/- 18.7 years, P
      < .01) and more frequently had underlying heart disease (64.9% vs 55.0%, P <
      .01): degenerative valve disease (11.5% vs 4.8%, P < .01), congenital heart
      disease (9.5% vs 4.2%, P < .01), and prosthetic valve IE (15.9% vs 8.5%, P <
      .01). Conversely, the prevalence of rheumatic valve disease was significantly
      less than in the 1992 survey (5.4% vs 13.0%, P < .01). CONCLUSIONS: The EIRA-2
      survey shows that the clinical profile of IE has changed in Argentina. Currently,
      patients with IE are older and have a higher frequency of underlying heart
      disease, degenerative valve disease, and prosthetic valve IE than previously. The
      incidence of staphylococcal IE has increased. Inhospital mortality remains high,
      suggesting that more aggressive measures are needed for the early identification,
      prevention, and treatment of IE.

PMID- 16442931
TI  - The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular
      disease.
AB  - There is accumulating evidence that inflammation is an important risk factor in
      cardiovascular disease (CVD). Elevated levels of the inflammatory marker high
      sensitivity C-reactive protein (hs-CRP) are associated with increased risk for
      CVD and diabetes mellitus. Adding hs-CRP to the definition of the metabolic
      syndrome has been shown to improve the prediction of CVD. Elevated hs-CRP levels
      may also be predictive of development of the metabolic syndrome. Current
      definitions of the metabolic syndrome differ, and cardiovascular risk appears to
      differ according to which component risk factors are present. Further studies are
      required to identify a widely accepted criterion for the syndrome that will
      optimally predict the risk of diabetes and CVD. It is possible that such a
      definition will include a measure of inflammation.

PMID- 16442932
TI  - Coronary artery disease in minority racial and ethnic groups in the United
      States.
AB  - Racial/ethnic minorities in the United States have a risk for coronary artery
      disease (CAD) that is at least equivalent to that in the white majority. African
      Americans have greater cardiovascular mortality rates and greater risk for early
      mortality caused by CAD. Risk may be associated with a greater clustering of risk
      factors in African Americans and other minority groups and may be associated with
      inadequate screening and evidence-based treatment of these groups in clinical
      practice. Data are beginning to emerge showing racial/ethnic variation in levels
      of the inflammatory marker high-sensitivity C-reactive protein, with higher
      levels in African Americans than in whites. There remain significant challenges
      to understanding racial/ethnic differences in cardiovascular risk factors and to
      including minority groups in clinical trials of therapeutic interventions,
      thereby ensuring optimal treatment for all.

PMID- 16442933
TI  - Inflammation in renal disease.
AB  - Inflammation is a component of the major modifiable risk factors in renal
      disease. Elevated high-sensitivity C-reactive protein (hs-CRP) levels have been
      shown to predict all-cause and cardiovascular mortality in patients dependent on
      dialysis and to predict worsening renal function in subjects without overt renal
      disease. Levels of hs-CRP are also predictive of hypertension, a major risk
      factor for renal disease, across all levels of blood pressure in subjects without
      initial hypertension. Many of the treatments used in patients with renal disease
      exert anti-inflammatory activities that constitute or contribute to their
      therapeutic effects. A number of studies have indicated that statin therapy
      exerts a renoprotective effect that is possibly mediated by anti-inflammatory
      activities.

PMID- 16442934
TI  - Current and future directions of cardiovascular risk prediction.
AB  - Coronary artery disease (CAD) prevention has moved beyond the secondary
      prevention of CAD events to the early identification and treatment of individuals
      thought to be at risk. Risk categories may be linked to the presence of other
      diseases, such as diabetes mellitus or noncoronary atherosclerotic disease, or to
      the finding of multiple risk factors on global risk assessment. Global risk
      assessment is now recommended as standard practice in cardiovascular disease
      prevention, and therapeutic strategies ranging from individuals at high risk
      (aggressive risk factor management) to those at low risk (periodic monitoring)
      are relatively straightforward. Further risk stratification appears to carry its
      greatest benefit for the large segment of the population comprising individuals
      who are asymptomatic and have "intermediate" risk on the basis of current global
      risk measures. Noninvasive techniques for assessing vascular wall status or
      cardiovascular function are useful in some of these individuals because they will
      enable a more accurate assessment of risk and thereby result in the risk status
      of the patient being raised to "high."

PMID- 16442935
TI  - Justification for the Use of Statins in Primary Prevention: an Intervention Trial
      Evaluating Rosuvastatin (JUPITER)--can C-reactive protein be used to target
      statin therapy in primary prevention?
AB  - The most important action of 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (statins) is their ability to lower levels of low-density lipoprotein
      (LDL) cholesterol. Statins have proved highly effective in reducing the risk of
      cardiovascular events in both primary and secondary prevention studies. However,
      the magnitude of risk reduction associated with statins is greater than that
      predicted on the basis of LDL cholesterol lowering alone. A likely explanation
      for this effect is the anti-inflammatory action of statins. Following the
      observation that high-sensitivity C-reactive protein (hs-CRP) is a powerful
      predictor of cardiovascular events, investigators in the Cholesterol and
      Recurrent Events (CARE) and Air Force/Texas Coronary Atherosclerosis Prevention
      Study (AFCAPS/TexCAPS) trials demonstrated that the magnitude of risk reduction
      associated with statin therapy was higher among those with elevated hs-CRP
      levels. In addition, there is accumulating evidence that statins lower plasma
      levels of hs-CRP in a manner largely independent of LDL cholesterol lowering. In
      contrast, little benefit has been demonstrated for statin therapy in the absence
      of both hyperlipidemia and inflammation. Justification for the Use of Statins in
      Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a
      large multinational, long-term, double-blind, placebo-controlled, randomized
      clinical trial designed to assess directly whether statin therapy (rosuvastatin
      20 mg/day) should be given to apparently healthy individuals with low LDL
      cholesterol levels but elevated hs-CRP levels--a critical issue for the
      prevention of cardiovascular disease. Support for the concept behind the JUPITER
      trial is also now available from several recent trials comparing different
      intensities of statin therapy on disease progression as well as clinical end
      points. These studies indicate that the hs-CRP level achieved after initiation of
      statin therapy may be as important as the LDL cholesterol level achieved. All of
      these data raise the possibility that hs-CRP could be used to target high-risk
      patients who may benefit from early statin use. Ongoing work will determine
      whether hs-CRP reduction, independent of LDL cholesterol reduction, results in a
      net clinical benefit.

PMID- 16442936
TI  - The role of government in health care: a societal issue.
AB  - The history of the role of government in health care is briefly reviewed and more
      fully discussed in the United States since the establishment of Medicare 40 years
      ago. Data and other evidence of the unintended consequences of this historic
      event are presented, identifying thorny and onerous issues that government has
      created, showing failed attempts at band-aid solutions, and suggesting that our
      present health care system is in disarray and cannot be rectified by the
      "incrementalism" approach. The establishment of a high-level commission jointly
      endorsed by the President of the United States and Congress is recommended to
      consider and analyze scrupulously all the components of our health care complex
      and provide a "roadmap" toward achieving a universal health care system that is
      culturally acceptable, affordable, and of optimal quality while avoiding its
      administration and total control by an ultimately rigid and unwieldy governmental
      or insurance-industry bureaucracy.

PMID- 16442937
TI  - Response to the role of government in health care: a societal issue.

PMID- 16442938
TI  - Commentary on the role of government in health care: a societal issue.

PMID- 16442939
TI  - Special commentary on the role of government in health care: a societal issue.

PMID- 16442940
TI  - Management of abdominal wound dehiscence using vacuum assisted closure in
      patients with compromised healing.
AB  - BACKGROUND: Restoration of the abdominal wall's integrity after postoperative
      wound dehiscence is frequently performed in a delayed fashion, necessitating a
      temporary dressing of the dehisced wound. METHODS: The Vacuum Assisted Closure
      (VAC) system (Kinetic Concepts, Inc., San Antonio, TX) was used in 21 patients
      with postoperative abdominal wound dehiscences that could not be closed
      immediately and who were at high risk for healing complications. The VAC device
      was used in conjunction with sharp debridement and it was maintained on a
      continuous mode with a negative pressure of -75 to -125 mm Hg. The dressing was
      changed every 2 days. VAC therapy was continued until the integrity of the
      abdominal wall was reestablished by surgical procedures or secondary healing.
      RESULTS: Thirteen patients had fascial dehiscence, and 9 of them had frank bowel
      exposure. Definitive fascial closure was performed in 9 of 13 patients with
      fascial dehiscence. Stable cutaneous coverage was subsequently achieved in all
      patients by local abdominal skin flap advancement (6), skin grafting (9), or
      secondary intention healing (6). Seven patients had part of their VAC therapy as
      outpatients. The complications included a low-output small bowel enterocutaneous
      fistula in 2 patients and partial skin graft loss in 1 patient. The fistulae
      resolved after operative treatment (1) or conservative treatment (1). CONCLUSION:
      Integration of the VAC system in the management of post-laparotomy wound
      dehiscence in patients with compromised wound healing appears to be successful
      and should be considered in such patients to provide a stable, healed wound.

PMID- 16442941
TI  - Reconstruction of the abdominal wall for incisional hernia repair.
AB  - BACKGROUND: Abdominal wall reconstruction with mobilization of autologous tissue
      has evolved as a reliable option for patients with incisional hernias. METHODS:
      With the aim of evaluating morbidity and recurrence rates in patients who
      underwent abdominal wall reconstruction for incisional hernia repair, we
      retrospectively reviewed the charts of 188 patients treated between 1996 and
      2003. RESULTS: Primary approximation of the fascial defect was achieved in 77%
      and was reinforced by either mesh placement or rectus muscle advancement. The
      remaining 23% were reconstructed either by mesh placement, components separation,
      or distant flap mobilization. Median follow-up was 15 months. Overall morbidity
      rate was 38%; recurrence rate was 13%. Dimensions of the hernia and
      intraoperative enterotomies were associated with postoperative complications.
      Lack of complete restoration of the myofascial abdominal wall continuity was
      associated with recurrence. CONCLUSIONS: In patients with incisional hernias,
      techniques involving autologous tissue mobilization are safe and associated with
      low recurrence rates.

PMID- 16442942
TI  - Multiple variables influence the educational value of surgical clerkship sites.
AB  - BACKGROUND: Students' satisfaction with the educational quality of a surgical
      clerkship is influenced by their experiences at assigned clinical sites. We
      sought to identify key variables perceived by students to be associated with
      educationally valued clerkship sites. METHODS: Between 1998 and 2002, third-year
      medical students completed a surgery site survey for each of the 2 sites on which
      they rotated during their required 2-month surgery rotation, representing a total
      of 16 sites. Students rated each site using a Likert scale on 8 educational
      variables as well as the overall educational value of the site. Students recorded
      the hours per week of direct instructional contact with attendings and, in the
      2001/2002 academic year, provided narrative comments regarding site-specific
      strengths and weaknesses. The relationship between site variables and overall
      educational value across all sites was examined by stepwise multiple regression
      analysis. Content analysis of narrative responses was performed to surface major
      strengths and weaknesses associated with site-specific educational value.
      RESULTS: From 1,377 completed surveys, representing an 87% completion rate, a
      statistically significant relationship was identified between sites' overall
      educational value and 6 variables. The most significant variables were as
      follows: "direct instructional contact with attendings in the operating room" and
      "quality of house staff teaching" (accounted for 33% and 13% of the total
      variance in educational value, respectively). Content analysis from 359 narrative
      responses, representing a 92% response rate, revealed 5 major categories, with
      operating room experience receiving the most "strength" comments (28.8%).
      CONCLUSIONS: Specific variables influencing the perceived educational quality of
      clerkship sites can be identified. The single largest influence emerging
      independently from both the quantitative and qualitative analyses was the
      students' experiences in the operating room. Emphasis on the educational
      experience in the operating room should be a priority when seeking to improve the
      educational value of clerkship sites.

PMID- 16442943
TI  - Do not roll the videotape: effects of the health insurance portability and
      accountability act and the law on trauma videotaping practices.
AB  - BACKGROUND: We hypothesized that trauma video practices would be affected as a
      result of Health Insurance Portability and Accountabilty Act (HIPAA) enactment.
      METHODS: A survey was distributed electronically to coordinators and/or directors
      of level 1 trauma centers. Centers were queried on demographics, trauma video
      use, and reasons for changes, if any, in their video practice patterns.
      Descriptive statistics and chi-square analysis were employed. RESULTS: Survey
      response rate was 75%. Prior to HIPAA, 58% of responding trauma centers used
      video compared to 18% now. On a Likert scale of 1-5, video analysis rated 3.80.
      For those using video currently, the most common purposes are education (91%) and
      quality assurance (83%). HIPAA has affected the way video is used at one third of
      these centers. Ten percent receive institutional review board approval for
      videotaping, 35% get patient consent, and more than half report capturing a poor
      patient outcome on tape. The most commonly cited reasons for stopping video use
      were HIPAA and legal concerns about patient privacy, consent, and discoverability
      (79%). Scarce resources were, in part, to blame at 70% of centers, while video
      technology was found to be ineffective at only 32%. CONCLUSIONS: A minority of
      level I trauma centers currently use video, although it is effective according to
      users. HIPAA and medicolegal concerns have affected its use at some centers and
      contributed to its abandonment at others.

PMID- 16442944
TI  - Predictors of cancer in patients with suspected pancreatic malignancy without a
      tissue diagnosis.
AB  - BACKGROUND: The aim of this study was to identify predictive factors for
      malignancy in patients undergoing surgery for suspected pancreatic cancer without
      a preoperative tissue diagnosis. METHODS: Patients were identified by
      International Classification of Diseases Ninth Revision and current procedural
      terminology codes, respectively, for pancreatic cancer and
      pancreaticoduodenectomy at a single tertiary referral center between January 1998
      and May 2004. Data were collected retrospectively by chart review. Multivariate
      analysis of potential predictive factors was performed. RESULTS: A total of 150
      patients underwent surgery for documented or suspected pancreatic malignancy; 102
      did not have a preoperative tissue diagnosis of cancer. Of these, 75 had
      neoplastic disease at surgery. Average weight loss was greater for those with
      malignancy (13.5 vs. 4.8 lbs; P = .014) as was mean bilirubin (6.1 vs. 3.3 mg/dL;
      P = .006). In multivariate analysis, a combination of weight loss >20 lbs,
      bilirubin >3 mg/dL, and CA 19-9 >37 U/mL had both a specificity and positive
      predictive value of 100% for predicting malignancy regardless of bile duct
      abnormalities or mass lesions on endoscopic retrograde cholangiopancreatography
      or endoscopic ultrasound, respectively. The positive predictive value decreased
      to 89.5% when any 2 of these findings were present. The presence of a mass on CT
      or EUS alone had a sensitivity of 84%; however, no other single finding had a
      sensitivity >65%. CONCLUSIONS: In patients suspected of having a pancreatic
      malignancy, weight loss, hyperbilirubinemia, and increased CA 19-9 level may be
      predictive of a final cancer diagnosis. Surgical exploration should be considered
      in these patients even in the absence of a preoperative tissue diagnosis.

PMID- 16442945
TI  - Preoperative endoscopic pancreatic stenting for prophylaxis of pancreatic fistula
      development after distal pancreatectomy.
AB  - BACKGROUND AND OBJECTIVE: Pancreatic fistula is a common complication of distal
      pancreatectomy (DP). Although various surgical procedures have been proposed for
      DP in an attempt to decrease the high incidence of pancreatic fistula, the
      prevention of pancreatic fistula remains a major problem in DP. Endoscopic
      pancreatic stenting for the treatment or prophylaxis of such a fistula has been
      rarely described. METHODS: We reviewed 9 patients who underwent preoperative
      endoscopic pancreatic stenting for the prophylaxis of pancreatic fistula
      development after DP. RESULTS: Preoperative endoscopic pancreatic stenting was
      successfully performed with a 7F stent in all the 9 patients. Two patients, both
      with intraductal papillary mucinous tumor, developed mild acute pancreatitis
      after the stent placement. None of the 9 patients developed pancreatic fistula.
      The pancreatic stent was removed from 8 to 28 days (mean 11 days)
      postoperatively. CONCLUSIONS: Preoperative endoscopic pancreatic stenting may be
      an effective prophylactic measure against pancreatic fistula development
      following DP in selected patients.

PMID- 16442946
TI  - Identifying patients at risk of compromised margins following breast conservation
      for lobular carcinoma.
AB  - BACKGROUND: The association of invasive lobular carcinoma with high rates of
      compromised margins in breast conservation makes choice of operation for these
      patients difficult. We sought to identify patients at risk of compromised margins
      following breast conservation surgery. METHODS: We reviewed all patients with
      invasive lobular and invasive ductal carcinoma over a 5-year period (1999-2004).
      The imaging, pathology and surgical details of patients with invasive lobular
      carcinoma undergoing breast conservation were analyzed. RESULTS: A total of 991
      patients with invasive ductal carcinoma and 150 patients with invasive lobular
      carcinoma were identified. Lobular carcinomas had a compromised margin rate of
      49% (n = 38/77) in breast conservation compared to 24% (n = 143/588) of ductal
      carcinomas (P < .0001). Mammographic size (P = .017), pathological size (P =
      .01), age (P = .03), multifocality (P < .0001), and lymphovascular invasion (P =
      .015) were significantly associated with compromised margins. CONCLUSION:
      Invasive lobular carcinoma has a 49% rate of compromised margins following breast
      conservation. Mammographic size greater than 1.5 cm and young age were
      preoperative factors predictive of compromised margins.

PMID- 16442947
TI  - Endoscopic retrograde cholangiography for intrabiliary rupture of hydatid cyst.
AB  - BACKGROUND: Hydatid disease affects most commonly the liver, and rupture into the
      bile ducts is a frequent complication, occurring in 5% to 25% of cases. These
      complications can cause major clinical problems either preoperatively or
      postoperatively with post-resectional abscess or prolonged biliary fistula. We
      reviewed our experience with preoperative endoscopic retrograde cholangiography
      (ERC) and the diagnosis of major cyst-biliary fistula. METHODS: During a 7-year
      period, 78 patients underwent surgery for hepatic hydatid disease. Ten patients,
      in whom a major intrabiliary rupture of the cyst was suspected on the basis of
      clinical and radiological criteria, underwent preoperative ERC, with clearing of
      the biliary tree. Endoscopic sphincterotomy was performed in 7 cases when the
      fluid contained daughter cysts or pus. Three patients, in whom the biliary
      content was fluid only, did not undergo sphincterotomy. One patient in whom a
      preoperative ERC was not feasible underwent operative transduodenal
      sphincterotomy. In all 11 patients the cyst was resected. Two patients underwent
      preoperative ERC, but no fistula was detected . They were compared with the
      remaining group of 67 patients who underwent resectional surgery during the same
      period, for apparently uncomplicated echinococcal cysts, and with an historical
      group of 569 patients operated on from January 1966 to January 1995. RESULTS:
      According to the clinical and radiological preoperative criteria, there were 2
      false positives. Preoperative ERC allowed visualization of the fistula, clearing
      of the biliary tree, and sphincterotomy in selected cases. The incidence of
      postoperative fistula was significantly decreased after the introduction of
      selective preoperative ERC, on the basis of preoperative clinical and
      radiological criteria. CONCLUSIONS: Preoperative ERC is very helpful in patients
      with cyst-biliary fistula, allowing visualization of the fistula and drainage of
      the biliary tree, and reducing the incidence of postoperative complications from
      11.1% to 7.6%. In selected cases it can solve the problem, without further
      surgical therapy.

PMID- 16442948
TI  - The clinical applications of mammary ductoscopy.
AB  - BACKGROUND: Mammary ductoscopy (MD) is a newly developed endoscopic technique
      that allows direct visualization and biopsy examination of the mammary ductal
      epithelium where most cancers originate. The procedure can be performed under
      local anesthesia in the office setting. This article reviews the rationale,
      current clinical applications, and limitations of MD. METHODS: A literature
      search was performed using Pubmed for indexed articles published over the past 30
      years using the key words "mammary ductoscopy," "breast ductoscopy," "ductal
      lavage," and "nipple aspiration." The most important articles were analyzed and
      discussed. RESULTS: MD is a useful diagnostic adjunct in patients with pathologic
      nipple discharge. Furthermore, it can reduce the number and extent of duct
      excision surgeries for pathologic nipple discharge. There is a clear need to
      design prospective clinical trials that evaluate the potential role of MD in
      breast cancer screening, guiding risk-reducing strategies, and as an adjunct to
      breast-conservation surgery. CONCLUSIONS: MD is useful in the management of PND,
      but its potential role in the early detection or management of breast cancer
      requires further investigation.

PMID- 16442949
TI  - Comparison of surgical outcomes of gastric cancer in elderly and middle-aged
      patients.
AB  - BACKGROUND: We compared clinicopathological features and results of surgery for
      gastric carcinoma in elderly and middle-aged patients to develop appropriate
      treatment for elderly patients with gastric carcinoma. METHODS: Surgical results
      were assessed for 135 elderly patients (over 75 years old) and 665 middle-aged
      patients (between 45 and 65 years old) with gastric cancer. RESULTS: Distinct
      characteristics of elderly patients were male predominance; macroscopically well,
      or ill-defined, histologically differentiated tumors; and advanced stage disease.
      There was a significant difference in overall survival between the groups for
      early stage carcinomas but no difference in cause-specific survival.
      Postoperative morbidities did not differ between the curatively resected patients
      in the 2 groups. Moreover, deaths from other cancers or comorbid disease were
      frequent among the elderly. CONCLUSION: Meticulous treatment and follow-up not
      only for gastric carcinoma but also for other diseases would improve survival in
      elderly patients, particularly those with early-stage tumors.

PMID- 16442950
TI  - Sentinel lymph node biopsy examination for breast cancer patients with clinically
      negative axillary lymph nodes after neoadjuvant chemotherapy.
AB  - BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy
      examination for breast cancer patients with clinically node-negative breast
      cancer after neoadjuvant chemotherapy (NAC) have been investigated under the
      administration of a radiocolloid imaging agent injected intradermally over a
      tumor. In addition, conditions that may affect SLN biopsy detection and false
      negative rates with respect to clinical tumor response and clinical nodal status
      before NAC were analyzed. METHODS: Seventy-seven patients with stages II and III
      breast cancer previously treated with NAC were enrolled in the study. All
      patients were clinically node negative after NAC. The patients then underwent SLN
      biopsy examination, which involved a combination of intradermal injection over
      the tumor of radiocolloid and a subareolar injection of blue dye. This was
      followed by standard level I/II axillary lymph node dissection. RESULTS: The SLN
      could be identified in 72 of 77 patients (identification rate, 93.5%). In 69 of
      72 patients (95.8%) the SLN accurately predicted the axillary status. Three
      patients had a false-negative SLN biopsy examination result, resulting in a false
      negative rate of 11.1% (3 of 27). The SLN identification rate tended to be
      higher, although not statistically significantly, among patients who had
      clinically negative axillary lymph nodes before NAC (97.6%; 41 of 42). This is in
      comparison with patients who had a positive axillary lymph node before NAC
      (88.6%; 31 of 35). CONCLUSIONS: The SLN identification rate and false-negative
      rate were similar to those in nonneoadjuvant studies. The SLN biopsy examination
      accurately predicted metastatic disease in the axilla of patients with tumor
      response after NAC and clinical nodal status before NAC. This diagnostic
      technique, using an intradermal injection of radiocolloid, may provide treatment
      guidance for patients after NAC.

PMID- 16442951
TI  - Late treatment-related complications in 214 patients with extremity soft-tissue
      sarcoma treated by surgery and postoperative radiation therapy.
AB  - BACKGROUND: We assessed the occurrence of long-bone fracture and other side
      effects in a group of 214 consecutive patients who underwent radical excision for
      soft-tissue sarcoma of the limb followed by postoperative irradiation. METHODS:
      Two hundred fourteen patients underwent postoperative irradiation after radical
      excision of soft-tissue sarcoma of the limb; 156 (73%) received postoperative
      brachytherapy (BRT) plus external-beam radiation therapy (EBRT), and 58 (27%)
      underwent postoperative EBRT only. All patients were followed-up for a median
      time of 4.5 years (range 3 months to 10 years). RESULTS: Seven patients developed
      bone fracture, which is considered severe morbidity; time between surgery and
      occurrence of fracture ranged between 10 and 72 months (average 31). Severe
      sclerosis with impairment of limb function was diagnosed in 5 and peripheral
      nerve damage in 3 patients. Wound complications were detected in 8 patients.
      CONCLUSIONS: In our series, no statistically significant correlation between bone
      fracture and clinical features or "technical" parameters was found, but all of
      the patients who experienced bone fracture (7 of 7) were postmenopausal women >55
      years old.

PMID- 16442952
TI  - A new technique of direct intra-abdominal pressure measurement: a preliminary
      study.
AB  - OBJECTIVE: The purpose of this study was to determine if a 14-F polyvinyl
      chloride (PVC) round drain is a reliable tool for direct intra-abdominal pressure
      measurement. DESIGN: A prospective interventional study. SETTING: Department of
      Surgery B, intensive care unit, recovery room, Hillel-Yaffe level II trauma
      center. METHODS: Forty patients undergoing abdominal surgery and treated
      postoperatively with intraperitoneal drains and intravesical catheters were
      included in this study. The indication for insertion of intraperitoneal drains
      and intravesical catheters was strictly medical. The decision of placing urinary
      bladder catheter and PVC round drain was done by a senior surgeon. Intra
      abdominal pressures were measured simultaneously through the intraperitoneal
      drain and the urinary catheter. Using a sterile technique, the intraperitoneal
      drain was disconnected from the drainage bulb and connected to an invasive blood
      pressure monitoring system. Intravesical pressures were measured by inserting 50
      mL into the bladder, and then the urinary catheter was connected to an invasive
      blood monitoring system. Measurements were done twice a day for 3 days or less if
      earlier removal of either the intraperitoneal drain or urinary catheters were
      medically indicated. RESULTS: Two hundred twenty-even simultaneous measurements
      were performed. Pressures as measured through the intraperitoneal drain were
      found to be significantly correlated to pressures as measured intravesically (r =
      0.962). CONCLUSIONS: Direct measurement of the intra-abdominal pressure via a 14
      F PVC round drain is a newly described technique. Our method is simple, safe, and
      credible. Future investigation is needed to confirm the reliability of this
      method for continuous postoperative measurement of the intra-abdominal pressure
      in selected patients.

PMID- 16442953
TI  - Development of assessing generic and specific technical skills in laparoscopic
      surgery.
AB  - BACKGROUND: Assessing live laparoscopic surgery using structured methodology is
      still in its infancy; however, it removes bias and subjectivity. We critique a
      new assessment tool for technical skills in laparoscopic surgery. METHODS: A
      hierarchical task analysis was done for laparoscopic cholecystectomy (LC), and a
      global assessment for generic and specific technical skills for LC was developed.
      Two experienced surgeons with >12 years of postgraduate experience assessed 50
      full-length LC operations blindly and independently. RESULTS: Five
      consultant/attending and 4 registrar/resident surgeons were recruited. Interrater
      reliability was k = 0.86 and k = 0.84 (P < .05) for generic and specific
      technical skills, respectively. Mean time for consultants was 32 minutes (range
      15 to 70) and for registrars was 53 minutes (range 20 to 90). Parametric Student
      t test analysis was significant for time between the 2 groups, P < .05.
      Nonparametric analysis of variance between the 2 groups for generic and specific
      technical skills was significant at P < .05. CONCLUSIONS: This assessment tool
      for live laparoscopic surgery may have face, content, concurrent, construct, and
      predictive validities for generic and specific technical skills. We aim to
      continue the study and expand assessment to other surgical techniques.

PMID- 16442954
TI  - Safety and hemostatic effect of recombinant activated factor VII in cirrhotic
      patients undergoing partial hepatectomy: a multicenter, randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Coagulopathy caused by cirrhosis may contribute to excessive bleeding
      during hepatectomy. We evaluated the hemostatic effect and safety of recombinant
      factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy.
      METHODS: Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo,
      administered intravenously 10 minutes before surgery and every second hour during
      surgery. The primary efficacy end points were the proportion of patients
      receiving red blood cell (RBC) transfusions and the amount of RBCs transfused.
      The RBC transfusion trigger was blood loss of 500 mL. Safety end points included
      thromboembolic and adverse events. RESULTS: No statistically significant effect
      of rFVIIa treatment on efficacy end points was observed. Serious and
      thromboembolic adverse events occurred at similar incidences in the study groups.
      CONCLUSIONS: Using blood loss as a transfusion trigger, the efficacy of rFVIIa in
      reducing the requirement for RBC transfusion was not established in this study.
      No safety concerns were identified.

PMID- 16442956
TI  - Therapeutic potentials of a novel method of dual-pulse gastric electrical
      stimulation for gastric dysrhythmia and symptoms of nausea and vomiting.
AB  - BACKGROUND: The aims of this study were to investigate the effects and mechanisms
      of a novel method of gastric electrical stimulation on the prevention of
      vasopressin-induced emetic response and gastric dysrhythmias. METHODS: Fifteen
      dogs (10 normal, 5 vagotomized) chronically implanted with gastric serosal
      electrodes were used in a 3-session study (vasopressin, vasopressin plus 2
      channel stimulation [DCS], and vasopressin plus dual-pulse stimulation [DPS]).
      RESULTS: Vasopressin induced gastric dysrhythmias and motion sickness-like
      symptoms (P < .05) and these effects were blocked partially with vagotomy. Both
      methods of DCS and DPS were capable of preventing vasopressin-induced gastric
      dysrhythmias (P < .05) and motion sickness-like symptoms (P < .05). The
      antiemetic effects of the proposed methods of DCS and DPS were abolished by
      vagotomy but their antidysrhythmic effects were not blocked by vagotomy.
      CONCLUSIONS: DCS and DPS are able to reduce vasopressin-induced gastric
      dysrhythmia and symptoms of nausea and vomiting. The vagal pathway is involved in
      the antiemetic effect but not the antidysrhythmic effect of the proposed methods
      of stimulation.

PMID- 16442955
TI  - Prediction of lymph node status in patients with superficial esophageal
      carcinoma: analysis of 160 surgically resected cancers.
AB  - BACKGROUND: The ability to predict lymph node metastasis in cases of superficial
      esophageal carcinoma before surgery would allow the identification of specific
      patients who do not require additional surgical resection after endoscopic local
      resection. METHODS: From 1980 to 2002 a total of 160 patients with superficial
      esophageal carcinoma, Tis or T1 tumors, underwent subtotal esophagectomy with
      lymph node dissection. On the basis of clinicopathologic data the risk factors
      for lymph node metastases are discussed. RESULTS: Patients with tumors that
      showed submucosal invasion, a nonflat shape, and lymphatic invasion had a higher
      risk for lymph node metastasis than the other patients. Multivariate analysis
      showed that the tumor depth and the macroscopic shape of the tumor were
      independent risk factors for lymph node metastases. CONCLUSIONS: Esophagectomy
      with lymph node dissection is recommended for patients with submucosal cancer.
      Local tumor resection can be recommended for patients with mucosal cancer without
      lymphatic invasion.

PMID- 16442958
TI  - Overnight activities of medical students on call: is it really educational?
AB  - BACKGROUND: To validate self-report of activities and to assess time allocation
      of medical students taking in-house call during their third-year surgery
      clerkship. METHODS: Informed consent was obtained from students who agreed to
      participate while rotating on the third-year surgery clerkship. Students were
      randomized to 1 of 2 groups, either the self-report group or the shadow group.
      All students kept a log of their activities during weekdays. Students randomized
      to the self-report group kept a log of their activities on nights (6 pm to 7 am
      weeknights) and weekends (7 am to 7 am Saturday and Sunday) when they were
      assigned to in-house call. Students randomized to the shadow group kept a log of
      their activities and also were shadowed while on call by a research assistant
      (observer) who recorded their activities. All students categorized each activity
      as patient-care activities related to educational objectives (educational),
      patient-care activities unrelated to educational objectives (noneducational), and
      personal care (personal). To validate self-report, student and observer logs were
      compared. Percentages of time engaged in educational versus other activities were
      compared between the shadowed and nonshadowed groups and among weekdays (WD),
      weeknights (WN), weekend days (WED), and weekend nights (WEN). RESULTS: A total
      of 34 students (16 shadow, 18 self-report) agreed to participate. Five (15%)
      students, all in the self-report group, did not turn in their logs. Data were
      available for the remaining 29 students for 138 shifts (WD, 44; WN, 46; WED, 24;
      WEN, 24). Observer and self-report were correlated highly for educational and
      personal activities, but not for noneducational activities. On WD, students
      averaged 76.1% of their time in educational activities, compared with 46.7%,
      63.3%, and 50.2% of their time while on WN, WED, and WEN, respectively (P <.05
      for WD vs. all others). Students spent between 9% and 14% of their time in
      noneducational activities, and between 9% and 49% of their time in personal
      activities during call shifts. CONCLUSIONS: This study validates student self
      report of activities while on surgery call. Students spend significantly more
      time engaged in educational activities during weekdays than any call shifts
      (weeknights, weekend days, weekend nights). This information can be used for
      curricular planning.

PMID- 16442957
TI  - Lecture versus standardized patient interaction in the surgical clerkship: a
      randomized prospective cross-over study.
AB  - BACKGROUND: Medical schools increasingly are incorporating the standardized
      patient (SP) interaction as a teaching and testing modality to prepare students
      for United States Medical Licensing Examination Step 2 Clinical Skills. Although
      SP interactions provide a safe environment in which to practice clinical skills,
      little is known about medical students' perceptions of the instructional SP
      interaction in comparison with the classic didactic lecture. We hypothesized that
      students would enjoy and value an instructional SP interaction more than a
      didactic lecture, and that this perception would be enhanced if the lecture
      immediately preceded the instructional SP interaction. METHODS: Students on the
      junior surgery clerkship from January to December 2004 were randomized into 2
      groups. Group A (n = 71) received an hour-long didactic lecture about peripheral
      vascular disease followed by a 20-minute instructional SP interaction in which
      the SP portrayed a patient with lower-extremity claudication. Group B (n = 72)
      received the SP interaction first, followed by the lecture. All students received
      an identical quiz about peripheral vascular disease after the second educational
      encounter, whether the SP interaction or the lecture. Student perceptions were
      surveyed by written questionnaire before and after the session by using a 5-point
      Likert scale, with 5 being the most favorable rating. Data (perceptions,
      performances on the quiz and the SP interaction, clerkship grades) were compared
      using the Student t test or the Mann-Whitney rank sums test. RESULTS: Although
      all students on average enjoyed and valued the lecture more than the SP
      interaction (P <.001), group A students enjoyed the SP interaction more than
      group B (3.3 +/- .9 vs. 2.8 +/- 1.0, P = .008), and they perceived the SP
      interaction as having more value to their overall education (3.3 +/- 1.0 vs. 2.8
      +/- 1.0, P = .004). Group A students performed statistically better on the
      physical examination (66% +/- 19% vs. 40% +/- 16%, P <.001) and communication
      portions (90% +/- 11% vs. 79% +/- 12%, P <.001) of the SP checklist than group B,
      but not on the history portion. Student confidence in their own history and
      physical examination skills increased similarly for both groups. CONCLUSIONS: The
      classic lecture format not only is enjoyed and valued as a learning tool more by
      our surgical clerkship students than the instructional SP interaction, but having
      a lecture just before an SP interaction increased perceived enjoyment and value
      of the SP interaction and enhanced performance on the SP checklist. These data
      suggest that educators can improve student perceptions and attitudes surrounding
      the instructional SP interaction by using strategically timed lectures.

PMID- 16442959
TI  - Use of a personal digital assistant to monitor surgery student work and sleep
      hours.
AB  - BACKGROUND: We developed a personal digital assistant (PDA)-based program to
      assess compliance with our medical student work hours policy, and to correlate
      work hours with sleep and performance. METHODS: Medical students on surgery
      clerkship logged real-time work and sleep hours for 1 week. Estimated work hours,
      clinical evaluations, and score on the National Board of Medical Examiners (NBME)
      surgery examination were recorded. RESULTS: Thirty-seven students logged work
      hours, which correlated poorly with estimated work hours and sleep hours. The
      majority of students overestimated work hours by a mean of 19.5 hours. Twenty
      four students transgressed written policy. Increased in-hospital study hours
      correlated with improved clinical ratings but poorer NBME examination scores.
      Increased operating room hours correlated with higher NBME examination scores.
      CONCLUSIONS: Medical students inaccurately estimate work hours; a PDA-based log
      facilitates hours monitoring. Unenforced work hour policies are frequently
      transgressed. Work activity patterns, but not total work hours, correlated with
      outcomes on standardized written tests and clinical ratings.

PMID- 16442960
TI  - Effective retention of primary survey skills by medical students after
      participation in an expanded Trauma Evaluation and Management course.
AB  - BACKGROUND: The Trauma Evaluation and Management (TEAM) module orients medical
      students to the initial assessment of an injured patient. At the Medical College
      of Wisconsin, a course based on expanded TEAM (eTEAM) was developed for junior
      medical students. This study determined whether eTEAM improved the ability to
      perform and retain primary survey skills. METHODS: Objective Structured Clinical
      Examination methodology was used to compare 2 groups of senior medical students 1
      year after receiving either a 2-hour lecture or eTEAM. RESULTS: Students
      receiving eTEAM performed the primary survey much better than those receiving
      lecture alone. The overall Objective Structured Clinical Examination scores did
      not differ between groups. CONCLUSIONS: Medical students participating in eTEAM
      retained the ability to perform a primary survey in proper sequence 1 year later
      better than students receiving the information in lecture format only.

PMID- 16442961
TI  - The utility of estrogen receptor, progesterone receptor, and Her-2/neu status to
      predict survival in patients undergoing hepatic resection for breast cancer
      metastases.
AB  - BACKGROUND: Hepatic metastases from breast cancer signal a dismal prognosis, with
      a median survival of 9.5 months. METHODS: Twenty breast cancer patients with
      liver metastases underwent hepatic resection, biopsy, or ablation between 1995
      and 2004. Hormone receptor status and Her-2/neu expression of primary and
      metastatic tumors were correlated with overall survival. RESULTS: At a mean
      follow-up of 39 months after hepatic resection, median survival was 32 months.
      Patients undergoing anatomic resection with or without ablation lived
      significantly longer than those undergoing more limited resections (46 vs. 25
      months, P = .016). Survival was significantly greater in patients with estrogen
      receptor (ER)-positive primary (P = .02) and metastatic (P < .004) tumors, Her
      2/neu-positive metastases (P = .02), </=2 hepatic metastases (P < .002), and age
      >50 years at metastasectomy (P = .02). CONCLUSIONS: The ER status of the primary
      tumor and ER and Her-2/neu status of hepatic metastases, in addition to other
      clinical factors, may help select patients who would benefit from hepatic
      metastasectomy.

PMID- 16442962
TI  - Using the supercharge technique to additionally revascularize the gastric tube
      after a subtotal esophagectomy for esophageal cancer.
AB  - BACKGROUND: Maintaining sufficient blood flow to the gastric tube after a
      subtotal esophagectomy for esophageal cancer is crucial for decreasing
      esophagogastric anastomotic leakage. METHODS: After subtotal esophagectomy for
      esophageal cancer, the supercharge technique was performed in 21 esophageal
      reconstruction patients to additionally revascularize the gastric tube using the
      splenic artery and vein, external carotid artery, and internal jugular vein.
      Operative results of the supercharge group were retrospectively compared with
      those of the control group (patients not receiving the technique). RESULTS: Both
      operation time and operative blood loss in the supercharge group were
      significantly longer and larger than those of the control group. However, the
      incidence of anastomotic leakage was significantly lower in the supercharge group
      than in the control group. CONCLUSION: This practical supercharge technique
      reduces leakage during esophageal anastomosis.

PMID- 16442963
TI  - "Clinical methods and team work: 1,000 years ago".

PMID- 16442964
TI  - Stapled-wedge gastroplasty.

PMID- 16442965
TI  - ACRM's evolving mission: opportunities to promote rehabilitation research.
AB  - This presidential address reflects on the history and mission of the American
      Congress of Rehabilitation Medicine (ACRM) and considers the benefits derived
      from joint ownership of Archives of Physical Medicine and Rehabilitation with the
      American Academy of Physical Medicine and Rehabilitation (AAPM&R). Much of ACRM's
      history has been distinguished by collaboration with AAPM&R on essential
      concerns. Evolving organizational priorities have resulted in distinct
      association missions that have consequences for joint ownership of Archives. The
      journal has grown in important ways in the past 86 years from a solo editor to an
      editorial board and to joint ownership and sponsorship of alternating issues. The
      quality of Archives has improved substantially in the past decade, with an
      improving impact factor and an increasing number of manuscript submissions. A new
      contract with the publisher provides an opportunity to consider the relationship
      between the Congress and Archives and what kind of benefit ACRM desires it to be
      for its members, to the larger community of physical medicine and rehabilitation
      (PM&R), and to the persons with disabilities we as PM&R professionals seek to
      serve. Archives is well positioned to fulfill ACRM's focus on promoting
      rehabilitation research and facilitating information dissemination and technology
      transfer. An internationally respected journal is an excellent means to
      disseminate rehabilitation research that promotes health, independence,
      productivity, and quality of life for people with disabling conditions. This new
      chapter in the relationship between Archives and the Academy and Congress
      provides several opportunities for rehabilitation research leadership. More than
      ever, Archives provides a premier mechanism to fulfill the Congress's mission and
      to promote our sense of community.

PMID- 16442966
TI  - The state of rehabilitation research: art or science?
AB  - Rehabilitation research has been criticized as not standing up enough to the
      rigors of scientific method to be called "science." The field has been portrayed
      as slow to promote its scientific achievements and to include them under the
      rubric of evidence-based rehabilitation. Following in the footsteps of
      psychology, rehabilitation as a broad-based discipline has faced many similar
      obstacles in achieving scientific status. Controversy exists about what exactly
      constitutes rehabilitation science versus its art and its respective
      multidisciplinary domains. The conception of these domains is directly related to
      current methods available to assess the state of the discipline and its research
      accomplishments. I used quantitative methods, such as randomized clinical and/or
      controlled trials (RCTs) and systematic reviews, to assess the status of
      rehabilitation research. Findings suggest that, as a field, rehabilitation makes
      significant contributions to science, measurable by the number and quality of
      RCTs and systematic reviews conducted so far on topics of critical importance for
      clinical care. In "artful" complement, qualitative approaches can be used as
      research tools to aid investigators in seeking knowledge beyond that obtained by
      quantitative methods, assessing many complexities associated with the various
      contexts of rehabilitation research. Other requirements to develop a common
      vision of rehabilitation science are also discussed.

PMID- 16442967
TI  - Inpatient rehabilitation outcome after hip fracture surgery in elderly patients:
      a prospective cohort study of 946 patients.
AB  - OBJECTIVE: To identify the factors associated with inpatient rehabilitation
      outcome after surgical repair of hip fracture in elderly patients. DESIGN: A
      noninterventional prospective cohort study. SETTING: Geriatric inpatient
      rehabilitation center in a tertiary university medical center in southern Israel.
      PARTICIPANTS: Patients (N=946) aged 65 years of age or older who were
      hospitalized for rehabilitation after surgery for hip fracture. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Functional studies by the FIM instrument
      and a broad spectrum of clinical, demographic, and social variables. Stepwise
      multiple regression was used to assess the relative contribution of the variables
      to the variance of the percentage change in the FIM score during the course of
      rehabilitation in relation to the severity of the functional impairment at its
      inception. RESULTS: Eight variables were significantly and independently
      associated with rehabilitation outcome. Prefracture FIM scale (standardized
      regression coefficient in multiple regression [beta]=.261, P<.001), serum albumin
      at discharge (beta=.222, P<.001), Folstein Mini-Mental State Examination
      (beta=.174, P<.001), visual impairment (beta=-.089, P=.002), dyspnea at mild
      exertion (New York Heart Association class III) (beta=-.080, P=.005), age (beta=
      .080, P=.007), poststroke motor impairment (beta=-.072, P=.011), and decreased
      serum folic acid (beta=-.055, P=.047). The total percentage of the explained
      variance of the primary rehabilitation outcome measure accounted for by these 8
      variables (adjusted R(2)) was 31.9%. CONCLUSIONS: The outcome of rehabilitation
      of elderly patients after surgical repair of hip fracture is associated with 4
      clinical and nutritional correctable parameters. The other 4 variables that are
      associated with the process cannot be corrected but may help predict outcomes and
      adjust expectations.

PMID- 16442968
TI  - Does gynecologic surgery contribute to low back problems in later life? An
      analysis of the women's health and aging study.
AB  - OBJECTIVE: To examine whether women with potential injuries to the abdominal and
      pelvic musculature from past gynecologic surgery are at higher risk for low back
      pain (LBP). DESIGN: Cross-sectional population-based study. SETTING: Eastern
      region of the city and county of Baltimore, MD. PARTICIPANTS: Disabled women
      (N=1002) aged 65 and older, 448 of whom reported gynecologic surgery who were
      participants in the Women's Health and Aging Study. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: LBP presence in the last year, LBP severity
      for the last month, and adjudicated lumbar diagnoses (disk disease, stenosis)
      were examined in relation to reports of surgical menopause or ovarian surgery
      adjusted for LBP risk factors. RESULTS: Women with surgical menopause experienced
      more moderate LBP (adjusted odds ratio [AOR]=1.59; 95% confidence interval [CI],
      1.1-2.3) than women without surgical menopause. Women with ovarian surgery also
      experienced more moderate LBP than women without ovarian surgery, but this
      association was not statistically significant (AOR=1.39; 95% CI, 0.96-2.09).
      Gynecologic surgery was not associated with an increased likelihood of lumbar
      disk disease or stenosis. CONCLUSIONS: Surgical menopause may increase the risk
      of moderate LBP. Further research is needed to determine how gynecologic surgery
      might influence low back pathology. Abdominal and pelvic muscle rehabilitation
      after gynecologic surgery may provide protection from LBP later in life.

PMID- 16442969
TI  - Stroke survivors' behavioral and psychologic symptoms are associated with
      informal caregivers' experiences of depression.
AB  - OBJECTIVE: To determine the impact of stroke survivors' behavioral and
      psychologic symptoms (BPS) on informal caregivers' experience of depression in
      the context of the caregiving situation. DESIGN: Cross-sectional survey using a
      structured quantitative interview. SETTING: Rehabilitation facility outpatient
      clinic, tertiary care facility outpatient clinic, and community care
      organizations. PARTICIPANTS: Ninety-four informal caregivers to stroke survivors
      completed standardized measurement instruments. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Measurement instruments included the Center for
      Epidemiological Studies Depression Scale, Brain Impairment Behavior Inventory
      Revised, Caregiver Assistance Scale, Caregiving Impact Scale, and Mastery scale.
      RESULTS: A substantial percentage (44.7%) of caregivers were at risk of clinical
      depression. Caregivers experienced more depression symptoms when they cared for
      stroke survivors exhibiting more BPS of memory and comprehension difficulties,
      provided less assistance, experienced more lifestyle interference, and had lower
      mastery (F(5,85)=26.02, P<.001, adjusted R(2)=.58). CONCLUSIONS: BPS exhibited by
      stroke survivors contribute to informal caregivers' experience of depression.
      These results can assist rehabilitation professionals to identify informal care
      providers who are at greater risk of experiencing emotional distress and,
      therefore, may benefit from intervention.

PMID- 16442970
TI  - Poststroke fatigue: course and its relation to personal and stroke-related
      factors.
AB  - OBJECTIVES: To describe the course of fatigue during the first year poststroke
      and to determine the relation between fatigue at 1 year poststroke and personal
      characteristics, stroke characteristics, and poststroke impairments. DESIGN:
      Inception cohort. SETTING: Rehabilitation center. PARTICIPANTS: Patients (N=167)
      with a first-ever supratentorial stroke admitted for inpatient rehabilitation.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Fatigue Severity Scale
      measured the presence and impact of fatigue at admittance for inpatient
      rehabilitation, as well as at 6 months and 1 year poststroke. RESULTS: At
      admission, 6 months and 1 year poststroke, fatigue was present in 51.5%, 64.1%,
      and 69.5% of the patients, respectively. Fatigue impact 1 year poststroke was
      greater among patients with more depressive symptoms, higher age, women, and
      patients with a locus of control more directed to powerful others. CONCLUSIONS:
      Because fatigue impact is an increasing problem during the first year poststroke,
      it deserves more attention in clinical practice and scientific research. Locus of
      control and depression are related to poststroke fatigue and might be important
      foci for future interventions.

PMID- 16442971
TI  - Participation survey/mobility: psychometric properties of a measure of
      participation for people with mobility impairments and limitations.
AB  - OBJECTIVE: To describe the development and psychometric properties of a self
      report survey of participation by people with mobility limitations, the
      Participation Survey/Mobility (PARTS/M). DESIGN: The information obtained during
      interviews and focus groups was used to develop items for the PARTS/M.
      Demographics and measures of disability, health, and functioning were collected.
      The PARTS/M was administered twice. SETTING: Primarily in the midwestern United
      States. PARTICIPANTS: Purposeful sample of 604 people with mobility limitations
      having a diagnosis of spinal cord injury, multiple sclerosis, cerebral palsy,
      stroke, or postpoliomyelitis. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: PARTS/M is composed of 20 major life activities that are placed in 6
      domains used in the activity/participation component of the International
      Classification of Functioning, Disability and Health: self-care; mobility;
      domestic life; interpersonal interactions and relationships; major life areas;
      and community, social, and civic life. For each activity, questions were asked
      about components of participation including frequency, health-related
      limitations, importance, choice, satisfaction, use of assistive technology, and
      use of personal assistance. RESULTS: PARTS/M domains and components of
      participation had good internal consistency and stability. Composite
      participation scores were developed for participation components and domains.
      CONCLUSIONS: PARTS/M is a reliable measure of some aspects of participation in
      major life activities for people with mobility impairments and limitations living
      in community settings.

PMID- 16442972
TI  - Early effects of the prospective payment system on inpatient rehabilitation
      hospital performance.
AB  - OBJECTIVE: To assess changes in utilization and financial performance for
      inpatient rehabilitation facilities (IRFs) that shifted from Medicare's cost
      based payment system to the IRF prospective payment system (PPS). DESIGN: A pre
      post nonequivalent comparison group design. The intervention group included IRFs
      that changed to the PPS in fiscal year 2002. The comparison group included IRFs
      that were paid under the cost-based system. SETTING: IRFs in the United States.
      PARTICIPANTS: Final sample included 120 IRFs, with 26 IRFs in the comparison
      sample. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Outcome measures
      included utilization (length of stay [LOS], total discharges, Medicare
      discharges) and financial performance (revenue, expenses, profitability, Medicare
      payment and cost). RESULTS: PPS IRFs experienced a smaller decline in LOS,
      whereas Medicare cost per discharge increased at a lower rate. PPS IRFs reduced
      operating costs per discharge, whereas profit margin had a greater increase.
      CONCLUSIONS: IRFs under PPS implemented cost controls that lead to lower
      operating costs below the fixed payment to profit under PPS. Discharge growth for
      PPS IRFs was similar to the comparison group. PPS facilities did not implement a
      strategy that attempted to admit more patients to increase Medicare payments.

PMID- 16442973
TI  - Performance of the disabilities of the arm, shoulder and hand outcome
      questionnaire and the Moberg picking up test in patients with finger joint
      arthroplasty.
AB  - OBJECTIVE: To compare the performance of the Disabilities of the Arm, Shoulder
      and Hand Outcome (DASH) Questionnaire and the Moberg Picking Up Test (MPUT) with
      other outcome measurement tools in assessing both hand function and aspects of
      general health in finger joint arthroplasty in patients with rheumatoid arthritis
      (RA). DESIGN: Case series, with an average follow-up duration of 104.9 months.
      SETTING: Orthopedic outpatient clinic at a university hospital. PARTICIPANTS: Of
      64 consecutive patients (21 dead, 6 lost to follow-up), 37 patients with 140
      spacers in 107 metacarpophalangeal and 33 proximal interphalangeal joints of 51
      hands were evaluated. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Hand
      function tests and general health measures. RESULTS: The DASH correlated with
      both hand function (Health Assessment Questionnaire: r=.72, P<.01; MPUT: r=0.6,
      P<.01) and general health (Medical Outcomes Study 36-Item Short-Form Health
      Survey subscales: r range, -.73 to -.31; P range, <.001 to <.05). The MPUT was a
      suitable tool for precision grip testing. CONCLUSIONS: The DASH has the advantage
      of being self-administered and assesses both functional and health aspects. It
      can be recommended as an instrument for a routine clinical follow-up for patients
      with hand surgery and RA. Additional tests should be applied when detailed
      information is needed.

PMID- 16442974
TI  - Deficits in upper-limb task performance in children with hemiplegic cerebral
      palsy as defined by 3-dimensional kinematics.
AB  - OBJECTIVE: To define upper-limb movement deficits in children with hemiplegia
      using 3-dimensional (3-D) kinematic analysis of functional tasks. DESIGN: Cohort
      study. SETTING: University gait laboratory. PARTICIPANTS: Ten children with
      hemiplegic cerebral palsy (mean age, 13.3y; range, 10-17y) and 10 control
      children (mean age, 9.8y; range, 6-12y). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: 3-D upper-limb movement analysis. RESULTS: 3-D kinematics
      detected clinically significant between-group differences. Children with
      hemiplegia were significantly slower than control children in time taken to
      complete tasks (P<.05) and achieved slower movement velocities (P<.05). Group
      differences in range of motion (ROM) occurred in all 3 tasks examined (hand to
      mouth, hand to head, reach). Children with hemiplegia had significantly less
      supination (P<.03) and shoulder flexion (P<.03) and increased compensatory trunk
      flexion (P<.01) compared with control data (hand-to-mouth task). The reach task
      highlighted restriction of elbow extension in children with hemiplegia (minimum
      elbow extension: hemiplegia, 24+/-18 degrees ; control, 3+/-7 degrees ).
      Completing tasks bilaterally did not alter performance of the tasks in children
      with hemiplegia. CONCLUSIONS: 3-D kinematics detected deficits in timing, ROM,
      and proximal compensatory strategies during upper-limb functional task
      performance in children with hemiplegia.

PMID- 16442975
TI  - Atomoxetine enhances a short-term model of plasticity in humans.
AB  - OBJECTIVE: To evaluate the role of 2 noradrenergic drugs in modulating use
      dependent plasticity in humans. DESIGN: Double-blind, randomized, and placebo
      controlled crossover design. SETTING: A laboratory in a hospital. PARTICIPANTS: A
      convenience sample of 10 healthy subjects. INTERVENTION: An established paradigm
      that measures motor memory as a short-term model of use-dependent plasticity.
      Subjects attended 3 sessions, separated by at least 1 week to allow drug washout.
      Subjects received atomoxetine (Strattera), venlafaxine (Effexor), or placebo.
      MAIN OUTCOME MEASURE: Increase in the proportion of movements into the training
      target zone (TTZ), an indicator of enhanced plasticity. RESULTS: Atomoxetine, but
      not venlafaxine, significantly increased movements into the TTZ. CONCLUSIONS:
      These results support a role for norepinephrine in enhancing cortical plasticity
      and suggest potential benefits in using these drugs for improving motor recovery
      after stroke.

PMID- 16442976
TI  - Comparison of electric stimulation methods for reduction of triceps surae
      spasticity in spinal cord injury.
AB  - OBJECTIVES: To compare the effect of 3 methods of electric stimulation to reduce
      spasticity of the triceps surae in patients with complete spinal cord injury
      (SCI) and to investigate the carryover effect. DESIGN: Placebo-controlled study
      with repeated measurements after the interventions. SETTING: Research department
      affiliated with a rehabilitation hospital in the Netherlands. PARTICIPANTS: Ten
      patients with a complete SCI were recruited from the outpatient population of the
      rehabilitation hospital. All subjects had American Spinal Injury Association
      grade A impairment scores, except for one, who had grade C. The patients had no
      voluntary triceps surae contractibility. INTERVENTIONS: Forty-five minutes of
      cyclic electric stimulation of the agonist, antagonist, or dermatome of the
      triceps surae or a placebo approach. MAIN OUTCOME MEASURES: Outcome measures were
      the Modified Ashworth Scale (MAS), clonus score, and the H-reflex and M wave
      (H/M) ratio. The electromyographic response to a stretch of the soleus over the
      whole range of motion was also determined. The magnitude and ankle angle at which
      the electromyographic response started were calculated. RESULTS: Stimulation of
      the agonist provided a significant reduction in the MAS compared with the placebo
      approach (P<.001). There was no significant change in the H/M ratio or the
      electromyographic response amplitude after any of the stimulation methods,
      whereas stimulation of the antagonist muscle resulted in a significant reduction
      in the ankle angle at which the electromyographic response started, compared with
      the placebo approach (P<.037). CONCLUSIONS: Triceps surae stimulation reduces the
      MAS for that specific muscle, whereas the angle at which the reflex starts
      changes after antagonist stimulation.

PMID- 16442977
TI  - Effects of treadmill exercise on transcranial magnetic stimulation-induced
      excitability to quadriceps after stroke.
AB  - OBJECTIVE: To determine characteristics of transcranial magnetic stimulation
      (TMS)-induced measures of central motor excitability to the paretic and
      nonparetic quadriceps muscles of chronic hemiparetic stroke patients in the
      context of a short-term, submaximal bout treadmill exercise. DESIGN: Cross
      sectional. SETTING: Motor control and gait biomechanics laboratory. PARTICIPANTS:
      Convenience sample of 11 patients including cohorts of treadmill untrained (n=8)
      and trained (n=3) stroke patients with chronic hemiparetic gait. INTERVENTION:
      Short-term submaximal treadmill exercise. MAIN OUTCOME MEASURES: Thresholds,
      amplitudes and latencies of TMS-induced motor evoked potentials at vastus
      medialis in paretic and nonparetic lower extremities. RESULTS: Baseline
      characteristics of the motor evoked potentials (MEPs) show significantly higher
      motor thresholds, longer latencies, and reduced amplitudes on the paretic side.
      In cross-sectional comparisons a group of treadmill-trained patients had greater
      paretic MEP amplitude changes after treadmill exercise versus paretic MEP
      responses from a group of untrained patients. CONCLUSIONS: These results indicate
      that treadmill training for 3 months or more may alter responsiveness of the
      lower-extremity central motor pathways to a short-term treadmill stimulus.

PMID- 16442978
TI  - The correlation between selected measurements from footprint and radiograph of
      flatfoot.
AB  - OBJECTIVES: To assess the subarch angle obtained from electronic footprints using
      a capacitive mat transducer system in children with flatfeet, to evaluate other
      foot arch indexes, and to compare the results with radiographic measurements.
      DESIGN: A cross-sectional study. SETTING: Rehabilitation clinic in a municipal
      hospital. PARTICIPANTS: Thirty-two children (age range, 7-13y) diagnosed with
      flatfeet. INTERVENTIONS: Radiographic measurements and foot shape measurements
      obtained from feet. MAIN OUTCOME MEASURES: Talo-first metatarsal angle,
      talocalcaneal angle, talo-horizontal angle, and calcaneal angle were obtained
      from radiographs. Subarch angle, arch indexes, and long plantar angle were all
      captured and calculated via a capacitive transducer plate. RESULTS: Correlations
      between the subarch angle and the talo-first metatarsal angle, talo-horizontal
      angle, and arch height were significant, as was the correlation between midfoot
      arch index and talo-horizontal angle. The forefoot arch index had no significant
      relationship with radiographic parameters. The talo-horizontal angle and arch
      height had significant relationships with the long plantar angle. CONCLUSIONS:
      Measurement of the subarch angle had significant correlation with the
      radiographic parameters in children with flatfeet and it was accurately and
      easily obtained from a capacitive forceplate. Measurement of the subarch angle
      can be a useful tool in the assessment and diagnosis of flatfoot.

PMID- 16442979
TI  - The effect of 30 minutes of passive stretch of the rat soleus muscle on the
      myogenic differentiation, myostatin, and atrogin-1 gene expressions.
AB  - The effect of 30 minutes of passive stretch of the rat soleus muscle on the
      myogenic differentiation, myostatin, and atrogin-1 gene expressions. OBJECTIVE:
      To evaluate the effect of passive stretch, applied for 30 minutes to the rat
      soleus muscle, on the myogenic differentiation (myoD), myostatin, and atrogin-1
      gene expressions. DESIGN: Case-controlled study. SETTING: University laboratory.
      ANIMALS: Fifty 12-week-old male Wistar rats. INTERVENTIONS: Six groups of animals
      were given a single stretch bout and were evaluated immediately and 8, 24, 48,
      72, and 168 hours later. Another 3 groups were evaluated immediately after 2, 3,
      and 7 stretches. An intact control group was also analyzed. MAIN OUTCOME
      MEASURES: The messenger ribonucleic acid (mRNA) levels of myoD, myostatin, and
      atrogin-1 were assessed by real-time polymerase chain reaction. RESULTS: Twenty
      four hours after a single session of stretch only, the myoD mRNA levels had
      increased compared with the control group, whereas an increase in the atrogin-1
      expression was observed after 2, 3, and 7 stretches. CONCLUSIONS: A single
      session of passive stretch increased the myoD gene expression, a factor related
      to muscle growth. Interestingly, daily stretches increased the atrogin-1 gene
      expression, a gene primarily associated with muscle atrophy. The results
      indicated that gene expression was responsive to the number of stretch sessions.

PMID- 16442980
TI  - Effect of heat in increasing the range of knee motion after the development of a
      joint contracture: an experiment with an animal model.
AB  - OBJECTIVE: To compare the effects of 2 different heat modalities, infrared and
      ultrasonic therapy, on a knee flexion contracture. DESIGN: In vivo, experimental,
      controlled study involving a rat knee joint contracture model that was
      immobilized using a ligature in flexion for 40 days. SETTING: Collegiate research
      laboratory. ANIMALS: Ninety-three adult male Wistar rats. INTERVENTIONS: After
      remobilization, rats were assigned to 3 treatment groups: stretching only (S),
      stretching with infrared therapy (S+IR), and stretching with ultrasonic therapy
      (S+US). Six treatment sessions were given in 2 weeks. MAIN OUTCOME MEASURES: The
      angle of maximum knee extension, wet-weight of triceps surae muscles, phase lag,
      and dynamic stiffness as mechanical responses were measured, and histologic study
      was conducted. RESULTS: Compared with the S group, both the S+IR and S+US groups
      exhibited a significant increase in range of motion (ROM) (P=.021, P=.008,
      respectively) and a tendency to decrease the phase lag, but there was no
      significant difference between the 2 heat-combined groups. There were no
      differences in the weights of the triceps surae muscles and in dynamic stiffness
      among the groups. CONCLUSIONS: Six treatment sessions of stretching with infrared
      or ultrasound were more effective than stretching without heat at increasing the
      ROM and decreasing the phase lag of a moderately severe joint contracture. The
      clinical implementation of heat is advocated to regain a normal ROM and
      mechanical property when experiencing a joint contracture.

PMID- 16442981
TI  - The effects of substance P on the biomechanic properties of ruptured rat
      Achilles' tendon.
AB  - OBJECTIVE: To determine whether injection of substance P into the paratendinous
      region of a ruptured and subsequently sutured rat Achilles' tendon alters the
      biomechanic properties of the tendon. DESIGN: Interventional animal study.
      SETTING: Animal laboratory at a university hospital. ANIMALS: Ninety-six 2-month
      old, male Sprague-Dawley rats. INTERVENTION: Injection of saline, substance P
      (10(-6)micromol/kg of body weight [BW] or 10(-8)micromol/kg BW) associated with
      neutral endopeptidase inhibitors, or neutral endopeptidase inhibitors alone into
      the paratendinous region of ruptured and subsequently sutured rat Achilles'
      tendons from the second until the sixth day postoperatively. MAIN OUTCOME
      MEASURES: Stress at maximal load and work to maximal load and stiffness. RESULTS:
      Stress at maximal load was higher in the groups injected with substance P than in
      the saline group in the first, second, and sixth weeks. Work to maximal load was
      higher from the second until the sixth weeks in the substance P-treated groups
      than in the saline group. Stiffness did not differ between the 4 groups in any of
      the weeks. CONCLUSIONS: Injection of substance P into the paratendinous region of
      ruptured and subsequently sutured rat Achilles' tendons improved tendon healing
      by enhancing stress at maximal load and work to maximal load. However, stiffness
      was not significantly affected.

PMID- 16442982
TI  - Relationships between performance-based tests and patients' ratings of activity
      limitations, self-efficacy, and pain in fibromyalgia.
AB  - OBJECTIVE: To investigate the relationship between performance-based tests,
      ratings of activity limitations, self-efficacy, and pain in fibromyalgia. DESIGN:
      Descriptive. SETTING: University hospital. PARTICIPANTS: Sixty-nine women with
      fibromyalgia (mean age, 45+/-7.8y). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The patients completed 4 performance-based tests focusing on muscle
      power function and 3 unloaded arm movements. The patients rated their activity
      limitations by means of the subscales of physical function (PF) and pain on the
      Fibromyalgia Impact Questionnaire (FIQ), the Medical Outcomes Study 36-Item Short
      Form Health Survey (SF-36), and the Arthritis Self-Efficacy Scale (ASES).
      Spearman correlation coefficient (rho) and multivariate regression analysis were
      conducted. RESULTS: The highest correlations were found between the 6-minute walk
      test (6MWT) (rho range, -.48 to .68) and the activity limitations and between
      hand grip strength (rho range, -.34 to .57) and the activity limitations. The
      regression analysis indicated that hand grip strength explained 25% of the
      variation in the SF-36 PF scale. The 6MWT plus endurance of the shoulder muscles
      explained 24% of the variation in the FIQ PF scale and the 6MWT plus active
      abduction of the shoulder explained 48% of the variation in the ASES function
      scale. Correlations between the performance-based tests and the activity
      limitations tended to be higher than those between performance and pain.
      CONCLUSIONS: The majority of the performance-based tests and the patients'
      subjective ratings of activity limitations showed significant relationships. The
      6MWT and hand grip strength, reflecting activity limitations in the SF-36, FIQ,
      and ASES, are recommended for use in clinical research and in the clinical
      examination when planning treatment for patients with fibromyalgia.

PMID- 16442983
TI  - Exercise training improves low-density lipoprotein oxidability in untrained
      subjects with coronary artery disease.
AB  - Exercise training improves low-density lipoprotein oxidability in untrained
      subjects with coronary artery disease. OBJECTIVE: To test the hypothesis that
      regular exercise alters low-density lipoprotein (LDL) oxidability in patients
      with coronary artery disease. DESIGN: Longitudinal study. SETTING: General
      hospital and community. PARTICIPANTS: Thirteen patients. INTERVENTIONS: Training
      program comprising running bouts twice weekly over 2 months. MAIN OUTCOME
      MEASURES: Plasma lipid profile, oxidized LDL, and rate (Ox(rate)) and amount
      (Ox(amount)) of LDL reaction products were measured at baseline and after 2
      months of training. Brachial artery endothelium-dependent and -independent
      vasodilation was assessed by use of ultrasound. RESULTS: Lipid profile and
      oxidized LDL remained unchanged, but mean Ox(rate) and Ox(amount) +/- standard
      deviation were reduced from 2.5+/-1.5nmol.mgLDL(-1).min(-1) and 120.3+/
      75.3nmol/mgLDL at baseline to 0.4+/-0.2nmol.mgLDL(-1).min(-1) and 21.3+/
      11.4nmol/mgLDL after training (P<.05), respectively. Brachial artery vasodilation
      was suggested to be improved, but statistical significance was not reached in the
      small cohort under study. CONCLUSIONS: Aerobic training enhances the resistance
      of LDL to oxidation in patients with coronary artery disease, which may play a
      role in the favorable effects of exercise.

PMID- 16442984
TI  - Self-reported treatments used for lower-limb phantom pain: descriptive findings.
AB  - OBJECTIVE: To examine the types and relative frequency of treatments used for
      lower-limb phantom limb pain (PLP), including both pharmacologic and
      rehabilitative interventions. DESIGN: Cross-sectional survey. SETTING: Community
      based survey from clinical databases. PARTICIPANTS: Community-based sample
      (N=255) of persons with lower-limb amputations. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Intensity of PLP and type and helpfulness of treatments
      (both past and present) used for PLP. RESULTS: Although 72% of the sample (n=183)
      reported current PLP, 53% of the respondents with PLP (and 38% of those with
      severe PLP) had never used treatment for PLP. Those who had used treatment
      reported greater pain severity and interference. The most commonly used treatment
      modality was analgesic medication, including acetaminophen, opioids, and
      nonsteroidal anti-inflammatory drugs. Of the treatments surveyed, only opioids
      and chiropractic care were rated as moderately to extremely helpful by the
      majority of those who had tried them, and many pain interventions had been
      discontinued. CONCLUSIONS: As hypothesized, a significant proportion of persons
      with PLP have not used treatment for this pain, and, among those who have used
      pain treatments, few treatments are perceived as substantially helpful. More
      research is needed to identify effective management strategies for PLP and to
      examine further patient perceptions of pain treatment.

PMID- 16442985
TI  - Self-reported changes to nighttime sleep after traumatic brain injury.
AB  - OBJECTIVES: To explore subjective sleep reports from people in the chronic stages
      of traumatic brain injury (TBI) and to examine the extent and nature of sleep
      complaints in this population. DESIGN: Survey. SETTING: All participants were
      community based at the time of data collection. PARTICIPANTS: Sixty-three
      subjects with TBI consecutively recruited after discharge from rehabilitation and
      63 age- and sex-matched controls from the general community. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: A 7-day self-reported sleep-wake diary
      assessing sleep and wake times, sleep onset latency, frequency, and duration of
      nocturnal awakenings and daytime naps; a general sleep questionnaire used to
      evaluate sleep changes and quality; and the Epworth Sleepiness Scale to measure
      daytime sleepiness. RESULTS: Group-wise comparisons showed a significantly higher
      frequency of reported sleep changes after TBI (80%) relative to the control group
      (23%), supporting previous findings. The TBI group reported more nighttime
      awakenings and longer sleep onset latency; these changes were more frequently
      reported by participants with TBI with milder injuries. Increased levels of
      anxiety and depression were associated with increased reporting of sleep changes.
      CONCLUSIONS: These findings confirm the experience of changes to sleep after TBI
      and may at least in part account for the reported increased daytime sleepiness in
      this population. Sleep disturbance should be addressed during rehabilitation.
      Treatments need to focus on correcting the underlying cause of the sleep problem
      and to address patients' subjective experiences of their sleep, possibly through
      education and mood stabilization.

PMID- 16442986
TI  - Bilateral and recurrent myositis ossificans in an athlete: a case report and
      review of treatment options.
AB  - An unusual case of recurrent myositis ossificans (MO) bilaterally in the
      hamstring muscles of a 47-year-old athlete secondary to trauma is presented with
      a review of the literature of current treatment options. MO is a common condition
      that occurs among athletes in association with muscle and/or tendon strain or
      contusion. After an extensive literature review, we believe this to be the first
      case reported of recurrent and bilateral MO in a nonsurgical setting from
      recurrent hamstring strains. Plain radiographs and physical examination revealed
      the appearance and chronology of this pathology. Treatment options to improve
      flexibility and decrease morbidity are discussed along with prophylaxis for
      future injury. Treatment of mobility and flexibility, rehabilitation goals and
      treatment with nonsteroidal anti-inflammatory drugs, bisphosphonates, and
      magnesium are discussed along with prophylaxis.

PMID- 16442987
TI  - Influenza diagnosis and treatment in veterans with spinal cord injury.
AB  - OBJECTIVE: To assess influenza diagnosis and treatment behaviors and prescribing
      practices for antiviral medications among spinal cord injury (SCI) practitioners.
      DESIGN: Anonymous cross-sectional survey of practitioners and retrospective
      review of administrative diagnostic and prescription databases. SETTING:
      Department of Veterans Affairs health care facilities. PARTICIPANTS: One hundred
      practitioners participated (response rate, 65%). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Strategies for diagnosing and treating influenza and type
      of antivirals prescribed. RESULTS: Ninety-seven percent of practitioners reported
      using clinical symptoms to diagnose a patient with influenza. The most common
      treatments included symptom relievers (94%), followed by antivirals (21%).
      Antivirals reportedly used included amantadine (64%), rimantadine (36%),
      oseltamivir (32%), and zanamivir (11%). Twenty-one prescriptions for antivirals
      were identified during the influenza season and all were for amantadine.
      CONCLUSIONS: Despite recommendations by the U.S. Centers for Disease Control and
      Prevention and high risks of respiratory complications after SCI, antiviral
      medications and diagnostic tests for influenza are seldom used in the treatment
      of influenza in this population. Research is needed to identify barriers to
      diagnosing and administering antivirals in people with SCI.

PMID- 16442988
TI  - Hemiplegic shoulder pain syndrome: interrater reliability of physical diagnosis
      signs.
AB  - OBJECTIVE: To determine the interrater reliability of shoulder physical diagnosis
      signs in the acute stroke rehabilitation setting. DESIGN: Prospective inception
      cohort. SETTING: Academic inpatient stroke rehabilitation service. PARTICIPANTS:
      People admitted to stroke rehabilitation service. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The Neer impingement test, Speed test, acromioclavicular
      shear test, Rowe shoulder score, and palpation. RESULTS: Two examiners evaluated
      46 consecutively admitted participants at 18.9+/-14.1 days after stroke.
      Percentage agreement was 78% or higher on all tests. The kappa statistic was in
      the fair to excellent interrater reliability range on all tests except those
      involving the acromioclavicular joint, for which findings were infrequent.
      CONCLUSIONS: Most of the shoulder physical diagnosis signs used in this study
      have sufficient interrater reliability for use in future clinical studies of
      hemiplegic shoulder pain.

PMID- 16442989
TI  - Office-based ultrasound-guided intra-articular hip injection: technique for
      physiatric practice.
AB  - Intra-articular hip injections are commonly used in the evaluation and treatment
      of hip disorders. Although these injections are typically performed with
      fluoroscopic guidance, ultrasound provides a viable alternative for ensuring
      accurate intra-articular needle placement. This report describes the technique
      for performing ultrasound-guided intra-articular hip injections in the context of
      an office-based physiatric practice. Ultrasound offers several advantages over
      fluoroscopy, including accessibility, compact size, lack of ionizing radiation
      exposure, and visualization of neurovascular and other soft-tissue structures.
      With appropriate training and experience, interested physiatrists can consider
      implementing ultrasound-guided injections into their clinical practices.

PMID- 16442990
TI  - Understanding the use of weights in the analysis of data from multistage surveys.
AB  - Understanding the use of weights in the analysis of data from multistage surveys.
      Large national surveys are powerful tools with which to examine a variety of
      important rehabilitation-related issues and are currently the only feasible
      method to study disability trends over time. Because it is impractical to draw
      simple random samples from the entire United States, national surveys, such as
      the Medicare Current Beneficiary Survey (MCBS), select random samples of
      subgroups of a population. Thus, respondents may have unequal probabilities of
      being included in the survey, and weighting must be used in the analysis before
      the results may be generalized to the entire United States. Surveys such as the
      MCBS are rich sources of data for rehabilitation medicine, and it can be expected
      that more research will be conducted using these data sources. Statistical
      analysis of these data should account for the sampling scheme used in data
      collection. We review the principles involved in the design of multistage
      samples, the calculation of weights, and their use in the data analysis, focusing
      on their importance in the estimation of population values. Our objective is to
      help readers to understand and interpret results of research articles using this
      methodology. Examples using the MCBS data are provided to clarify the concepts
      presented in the article.

PMID- 16442991
TI  - Women with cerebral palsy and breast cancer screening by mammography.
AB  - Women with cerebral palsy and breast cancer screening by mammography. We
      emphasize the need to identify specific barriers to participation in breast
      cancer screening by mammography experienced by women with cerebral palsy (CP).
      Mammography screening has been found to reduce mortality rates by 30%, but women
      with disabilities such as CP underuse this important preventive medicine
      facility, potentially leading to delay in diagnosis of breast cancer and a less
      favorable prognosis. Because equity in health care is compromised through
      underutilization by these women, barriers to participation and successful
      outcomes must be investigated. Barriers such as appropriate information,
      transport, and assistance prevent women with CP from getting to the facility.
      Once there, communication difficulties, physical limitations, psychologic
      barriers, and staff attitudes become barriers to a successful outcome. Education
      for health personnel as well as adaptation of the mammographic technique to suit
      the physical limitations of women with CP are critical to increasing
      participation and ensuring successful outcomes. Importantly, there is a need to
      identify women for whom having a mammogram is not an option and for whom
      alternative breast screening methods should be provided.

PMID- 16442992
TI  - Reliability of center of pressure measures of postural steadiness.

PMID- 16442994
TI  - Analysis and reduction of the uncertainty of the assessment of children's lead
      exposure around an old mine.
AB  - Exposure to lead is a special problem in children, because they are more highly
      exposed than adults and because this pollutant, which accumulates in the body,
      induces neurobehavioral and cognitive effects. The objective of this study was to
      determine the probability density of the lead exposure dose of a 2-year-old child
      around an old mine site and to analyze its uncertainties, especially those
      associated with the bioavailability of lead in soil. Children's exposure was
      estimated indirectly from environmental samples (soils, domestic dust, water,
      air) and parameters (volume inhaled, body weight, soil intake rate, water intake,
      dietary intake) from the literature. Uncertainty and variability were analyzed
      separately in a two-dimensional Monte Carlo simulation with Crystal Ball
      software. Exposure doses were simulated with different methods for accessing the
      bioavailability of lead in soil. The exposure dose per kilogram of body weight
      varied from 2 microg/kgday at the 5th percentile to 5.5 microg/kgday at the 95th
      percentile (and from 2 to 10 microg/kgday, respectively, when ignoring
      bioavailability). The principal factors of variation were dietary intake, soil
      concentrations, and soil ingestion. The principal uncertainties were associated
      with the level of soil ingestion and the bioavailability of lead. Reducing
      uncertainty about the bioavailability of lead in soil by taking into account
      information about the type of mineral made it possible to increase our degree of
      confidence (from 25% to more than 95%) that the median exposure dose does not
      exceed the Tolerable Daily Intake. Knowledge of the mineral very substantially
      increases the degree of confidence in estimates of children's lead exposure
      around an old mining site by reducing the uncertainty associated with lead's
      bioavailability.

PMID- 16442995
TI  - Preliminary risk assessment of the lipid-regulating pharmaceutical clofibric
      acid, for three estuarine species.
AB  - Clofibric acid is the active metabolite of several fibrate drugs prescribed to
      reduce blood cholesterol levels. It is persistent and widely detected in the
      environment. Clofibric acid toxicity was assessed using three estuarine
      organisms: an alga (Dunaliella tertiolecta), a crustacean (Palaemonetes pugio),
      and a fish (Fundulus heteroclitus). Mortality and sublethal physiological
      responses (protein, lipid, cholesterol, and cytochrome P450 levels) were
      examined. Clofibric acid did not significantly affect cell density or growth rate
      of D. tertiolecta (concentrations 1000 microg/L). Survival of P. pugio and F.
      heteroclitus were also unaffected at clofibric acid concentrations 1000 microg/L.
      In addition, no significant changes in the sublethal test endpoints were found.
      An additional chronic (17-day) exposure of F. heteroclitus to clofibric acid (10
      microg/L) was conducted and found no effects on survival or sublethal endpoints.
      The rabbit polyclonal CYP450 4A antibody did cross react with F. heteroclitus,
      demonstrating that a CYP4A-like isoform is present in this teleost species and
      may be used in future induction studies. Clofibric acid, however, did not alter
      CYP4A levels in F. heteroclitus. Measured concentrations in the environment have
      not exceeded 10 microg/L. Therefore, the results of this study indicate a low
      risk of adverse effects from environmental exposure to clofibric acid for the
      species tested.

PMID- 16442996
TI  - Lead blood concentrations and renal function evaluation: study in an exposed
      Mexican population.
AB  - The relation of blood Pb concentrations and renal dysfunction has been reported
      in association with interstitial fibrosis, tubular atrophy, and decreased
      glomerular filtration. In this report information about blood Pb concentrations
      and renal function tests in a population from Oaxaca, Mexico is analyzed. The
      main changes found were that males had higher blood Pb concentrations than
      females (P<0.0012); the leading variables associated with this were occupation
      (glazed pottery workers, P=0.0001) and the use of glazed pottery for preparing
      meals (P=0.0000). Variables that better explain uric acid variability were blood
      Pb concentrations, sex, weight, and height (r2=0.23). Hyperuricemia was
      associated with blood Pb concentrations above 40 microg/dL (OR=1.74, 95% CI, 1.12
      2.61). SCr was associated with sex, age, and blood Pb, with coefficient r2=0.12.
      Our findings might be related to inadequate control of oven emissions, a
      situation that will require further analysis and the implementation of preventive
      measurements for the nonoccupational exposed population.

PMID- 16442997
TI  - Adverse effects of childhood lead poisoning: the clinical neuropsychological
      perspective.
AB  - Elevated blood lead levels in children can result in brain injury and, as a
      consequence, have negative effects on cognitive functioning and behavior. Risk
      assessment studies have focused on psychological measures, especially IQ, and
      also school achievement and behavioral adjustment as endpoints. Such studies,
      like epidemiological work in other areas, by necessity examine effects in large
      groups rather than in individuals. Since the peer-reviewed literature primarily
      describes those adverse effects noted in epidemiological studies, little or no
      attention has been directed to what is observed in the individual. The present
      review describes the presentation of individual lead-poisoned children from the
      perspective of the clinical neuropsychologist. The sequelae of lead poisoning
      typically observed in evaluation of individuals provide information in addition
      to that gained from risk assessment studies and has implications for the
      mechanisms and treatment of this disease. In addition, attention to certain
      aspects of individual case presentation does provide information relevant to
      issues of public health.

PMID- 16442999
TI  - HgbA1c and glucose control: we cannot play it straight with patients.

PMID- 16443000
TI  - Meta-analysis: Methods, strengths, weaknesses, and political uses.
AB  - The general methodology, strengths and weaknesses, and political uses of meta
      analysis are examined. As a systematic study of all studies that have been
      conducted to answer a specific question or hypothesis, meta-analysis is strong in
      revealing structural flaws and sources of bias in primary research and in posing
      promising research questions for future study. It cannot exceed, however, the
      limits of what is reported by primary researchers. Meta-analysis is particularly
      challenged to quantify the size of a common effect of treatment across reported
      trials because of (1) the clinical diversity of the trials and (2) the myriad of
      potential differences among patients with varying characteristics within the
      trials. Without access to the original data of reported trials, meta-analysis
      cannot overcome the bias of underpowered trials toward overstatement of the size
      of main treatment effects, nor the tendency for such trials to falsely conclude
      there were no statistically significant adverse events. Although severely
      compromised by ghost-written or honorary-authored reports of primary research,
      meta-analysis can make use of its methods to focus on the conflicts of interest
      and likely sources of bias of such research and make known what precautions
      should be taken by would-be consumers. Examples show how meta-analysis has
      clarified thinking about the off-label use of selective serotonin reuptake
      inhibitors for treating child and adolescent depression, use of low-tidal volume
      respirator assistance for acute lung injury and acute respiratory distress
      syndrome patients, and the long-term use of COX-2 inhibitors for relieving
      arthritic pain. Recommendations are made for Congressional action.

PMID- 16443001
TI  - The relationship between 24-hour integrated glucose concentrations and %
      glycohemoglobin.
AB  - OBJECTIVE: Since glycohemoglobin values are widely used clinically as a surrogate
      for average glucose concentration over an extended period of time, we decided to
      determine the actual relationship between 24-hour integrated glucose values and
      percent total glycohemoglobin (%tGHb) in cohorts of people with and without
      diabetes. RESEARCH DESIGN AND METHODS: In 48 people without known diabetes with
      known stability of fasting glucose over a 1-year period of time, the calculated
      24-hour integrated glucose concentration was compared with their %tGHb. In 15
      normal young medical students, the glucose area response was determined from 46
      venous blood samples obtained during a 24-hour period and compared with their
      %tGHb. In 18 people with type 2 diabetes, interstitial glucose concentrations
      were monitored using the Continuous Glucose Monitoring System (Medtronic MiniMed,
      Inc., Sylmar, Calif) for 3 days at 20-day intervals over 100 days. %tGHb was
      performed at 20-day intervals simultaneously. In 29 people with untreated type 2
      diabetes, glucose area response was determined from 46 venous blood samples
      obtained during a 24-hour period and compared with their %tGHb after being on a
      standardized diet provided to the subjects for at least 5 weeks. The %tGHb and 24
      hour profiles were stable. RESULTS: There was an excellent correlation between
      the mean 24-hour glucose concentration and the %tGHb among subjects with
      diabetes. The correlation was poor among subjects without diabetes. The
      relationship was curvilinear when plotted as a single group. Alternatively when
      data from subjects with or without diabetes were plotted separately, the slopes
      were identical but the y-intercepts were different. CONCLUSION: The relationship
      between the mean glucose concentration integrated over an extended period of time
      and the %tGHb is not linear. The reason for this nonlinearity remains to be
      determined. This non-linearity needs to be considered in the clinical
      interpretation of %tGHb (and probably HbA(1c)) in reference to glucose values.

PMID- 16443002
TI  - Relationships among tumor burden, tumor size, and the changing concentrations of
      fibrin degradation products and fibrinolytic factors in the pleural effusions of
      rabbits with VX2 lung tumors.
AB  - The VX2 tumor is derived from a papilloma virus-induced rabbit epithelial cell
      line. If VX2 tumor cells (trapped in a plasma clot) are introduced intravenously
      into NZW rabbits, the cells lodge in the lung capillary bed and produce tumors.
      Independently of the tumor burden (ie, the total tumor weight per rabbit),
      approximately 15% of rabbits with VX2 lung tumors accumulate an effusion in the
      interpleural space and this pleural effusion contains products of hemostasis. We
      hypothesized that these products were of intra-tumoral origin and that they
      changed in concentration as tumor burden increased. Interrelationships among lung
      , tumor-weights, and pleural effusion volumes, and the concentrations of
      fibrinolytic factors, their catabolic products, and other proteins of pleural
      effusions were measured in rabbits with a wide range of tumor burdens. Positive
      correlations between tumor burden and total lung weight and between pleural
      effusion volume and net lung weight suggested that interstitial fluid from the
      stroma of tumors passed directly into the extravascular space of the lung(s) and
      into the interpleural space(s). Analyses of pleural effusions indicated that
      plasminogen-, alpha(2)-antiplasmin-, and plasminogen activator inhibitor-1
      related proteins, urokinase-like- and tissue-plasminogen activator activities,
      and vascular endothelial growth factor increased in concentration up to a tumor
      burden of approximately 20-25 g. Plasmin activity and intact fibrinogen were
      absent. The concentration of fibrin(ogen) degradation products did not change
      significantly up to a tumor burden of approximately 25 g but increased
      substantially as tumor burdens exceeded 25 g. In conclusion, interstitial fluid
      from tumors enters the extravascular space of the host and may accumulate with
      fluid from non-tumor sources as a pleural effusion. The concentrations of
      fibrinolytic factors and their products in pleural effusions reflect the tumor
      burden of the rabbit. Conceivably, the components of a malignant effusion contain
      much information about the extent of tumor growth.

PMID- 16443004
TI  - H+-ATPase activity in selective disruption of H+-K+-ATPase alpha 1 gene of mice
      under normal and K-depleted conditions.
AB  - The outer medullary collecting duct (OMCD) plays an important role in acid-base
      homeostasis by two luminal proton ATPases, H(+)-ATPase and H(+)-K(+)-ATPase
      (HKA), both of which are in the intercalated cells (ICs) of OMCD. We showed
      previously that HKAalpha1 (gastric H(+)-K(+)-ATPase) activity is the essential
      H(+)-K(+)-ATPase activity under normal conditions, and that HKAalpha2 (colonic
      H(+)-K(+)-ATPase) is induced and mediates increased proton-secretion under K
      depleted conditions. To better understand the role of H(+)-ATPase (potassium
      independent) in acid secretion and the relationship between H(+)-ATPase and a
      specific HKA isoform, we examined H(+)-ATPase activity in the H(+)-K(+)
      ATPasealpha1 knockout (KO) mice under normal and K-depleted conditions. Mice were
      fed a potassium-free diet and studied after 7 days. Segments of the OMCD were
      perfused in vitro, and intracellular pH (pH(i)) was measured by ratiometric
      fluorescence microscopy using the pH-sensitive indicator BCECF-AM. The isolated
      OMCD tubules obtained from mice fed a potassium-free diet were examined by
      fluorescent immunocytochemistry with an antibody to the 31-kDa subunit of H(+)
      ATPase (E-11) and were compared with those obtained from a normal diet. In the
      absence of Na(+) and K(+), the H(+)-ATPase-mediate pH(i) recovery rates were 6.7
      +/- 1.1 x 10(-4) units/s (n = 7 ICs) in wild-type (WT) mice and increased to 8.7
      +/- 1.8 x 10(-4) (P < 0.05; n = 6) in HKAalpha1 KO mice. K-independent proton
      transport activity was significantly inhibited by the H(+)-ATPase inhibitor
      bafilomycin A(1) (BAF, 10 nM) with luminal applied in both WT and KO mice.
      Comparison of the results indicated upregulation of BAF-sensitive H(+)-ATPase
      activity in KO mice. To determine the intracellular localization of H(+)-ATPase
      in the intercalated cells of OMCD, we dissected the OMCD and performed
      fluorescent immunocytochemistry with the H(+)-ATPase antibody in the WT and KO
      mice. In the WT mice, on normal diet, H(+)-ATPase staining distributed diffusely
      throughout the intercalated cells and was slightly polarized to the apical plasma
      membrane in the KO mice, consistent with increase in the H(+)-ATPase-mediate
      pH(i) recovery in the KO mice. One week of a potassium-free diet resulted in a
      significant increase in the degree of H(+)-ATPase polarization at the apical
      plasma membrane in both WT and KO mice. Hypokalemia stimulates H(+)-ATPase in the
      intercalated cells of OMCD of both WT and KO mice. The enhanced activity of H(+)
      ATPase plays an important role in compensatory proton secretion in the HKAalpha1
      KO mice under normal conditions.

PMID- 16443003
TI  - Characterization of the urinary albumin degradation pathway in the isolated
      perfused rat kidney.
AB  - This study examines the existence of the urinary albumin degradation pathway and
      the proposed role of receptor-mediated endocytosis in this process using the
      isolated perfused rat kidney (IPK) model. Albumin-derived peptides in IPK urine
      are analyzed in terms of their relative size distribution using radioactivity and
      absorbance at 214 nm, and their susceptibility to trypsin digestion. The effects
      of perfusing kidneys with concanamycin A and myristoyl trimethyl ammonium bromide
      (MTMAB), inhibitors of the receptor-mediated endocytosis regulators vacuolar-type
      H(+) ATPase (v-ATPase) and dynamin GTPase, respectively, are examined. Normal IPK
      urine contains mildly degraded (defined as approximately 10-40 kDa; 43.0 +/-
      8.3%) and heavily degraded (defined as <10 kDa; 22.6 +/- 7.7%) albumin peptides
      as well as intact albumin (34.5 +/- 4.1%). The relative size distribution of the
      peptides is similar by radioactivity and absorbance at 214 nm, and both profiles
      are reduced to very small peptides following trypsin digestion. Administration of
      concanamycin A or MTMAB causes a significant increase in the proportion of intact
      albumin (concanamycin A: 55.8 +/- 11.6%; MTMAB: 50.0 +/- 11.9%) excreted compared
      with normal IPK urine. This coincides with a reduction in the proportion of
      mildly (concanamycin A: 27.6 +/- 9.8%; MTMAB: 39.9 +/- 11.5%) and heavily
      degraded (concanamycin A: 16.6 +/- 7.4%; MTMAB: 10.0 +/- 2.5%) albumin present
      and is not associated with changes in glomerular permeability to albumin because
      no significant change is observed in the fractional clearance of Ficoll (radius
      range 20-60 A) in the presence of concanamycin A. This study demonstrates the
      existence of albumin peptides in IPK urine and suggests that receptor-mediated
      endocytosis plays a role in urinary albumin degradation.

PMID- 16443006
TI  - First Annual Academic Surgical Congress, February 7-11, 2006, San Diego,
      California, USA. Abstracts.

PMID- 16443008
TI  - Fetal magnetoencephalography: viewing the developing brain in utero.

PMID- 16443009
TI  - Magnetoencephalography in studies of infants and children.

PMID- 16443010
TI  - Let's talk together: memory traces revealed by cooperative activation in the
      cerebral cortex.

PMID- 16443011
TI  - Human communication investigated with magnetoencephalography: speech, music, and
      gestures.

PMID- 16443012
TI  - Combining magnetoencephalography and functional magnetic resonance imaging.

PMID- 16443013
TI  - Beamformer analysis of MEG data.

PMID- 16443014
TI  - Functional connectivity analysis in magnetoencephalography.

PMID- 16443015
TI  - Human visual processing as revealed by magnetoencephalography.

PMID- 16443017
TI  - Striking the right balance between privacy and public good.

PMID- 16443016
TI  - A review of clinical applications of magnetoencephalography.

PMID- 16443018
TI  - Making progress towards leprosy elimination.

PMID- 16443019
TI  - Cough guidelines choke on evidence.

PMID- 16443020
TI  - Prevention of sudden unexpected infant death.

PMID- 16443022
TI  - Seeking equity in maternal health.

PMID- 16443021
TI  - Eat your fruit and vegetables.

PMID- 16443023
TI  - Sick children deserve a better deal.

PMID- 16443024
TI  - Resuscitation guidelines.

PMID- 16443025
TI  - A 15th grand challenge for global public health.

PMID- 16443026
TI  - Long-acting beta2 agonists and paediatric asthma.

PMID- 16443027
TI  - David Nabarro: mobilising the UN to tackle avian influenza.

PMID- 16443028
TI  - Origin of bovine spongiform encephalopathy.

PMID- 16443029
TI  - In praise of Japanese research.

PMID- 16443031
TI  - Origin of bovine spongiform encephalopathy.

PMID- 16443032
TI  - Gefitinib for refractory advanced non-small-cell lung cancer.

PMID- 16443033
TI  - Internet-based eye care.

PMID- 16443034
TI  - Gefitinib for refractory advanced non-small-cell lung cancer.

PMID- 16443035
TI  - Transfer of mouse embryonic stem cells to sheep myocardium.

PMID- 16443036
TI  - Towards a science of community engagement.

PMID- 16443037
TI  - Antivirals for influenza in healthy adults: systematic review.
AB  - BACKGROUND: Use of antivirals is recommended for the control of seasonal and
      pandemic influenza. Our aim was to review the evidence of efficacy,
      effectiveness, and safety of registered antivirals against naturally occurring
      influenza in healthy adults. METHODS: We searched various Databases to October,
      2005, and contacted manufacturers and corresponding authors. We included
      randomised controlled trials comparing prophylactic (n=27) or treatment (n=27)
      efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis
      and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For
      treatment trials, because of inconsistent and non-standardised reporting, we
      expressed continuous outcomes either as means or as hazard ratios. FINDINGS: We
      included 51 reports of 52 randomised controlled trials. Amantadine prevented 61%
      (95% CI 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like
      illness, but caused nausea (OR 2.56, 1.37-4.79), insomnia and hallucinations
      (2.54, 1.50-4.31), and withdrawals because of adverse events (2.54, 1.60-4.06).
      There was no effect on asymptomatic cases (RR 0.85, 0.40-1.80). In treatment,
      amantadine significantly shortened duration of fever compared with placebo (by
      0.99 days, -1.26 to -0.71), but had no effect on nasal shedding of influenza A
      viruses (0.93, 0.71-1.21). The fewer data for rimantadine showed comparable
      effects. In prophylaxis, compared with placebo, neuraminidase inhibitors have no
      effect against influenza-like illness (1.28, 0.45-3.66 for oral oseltamivir 75 mg
      daily, 1.51, 0.77-2.95 for inhaled zanamivir 10 mg daily). Higher doses appear to
      make no difference. The efficacy of oral oseltamivir 75 mg daily against
      symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled
      zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor
      appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR
      1.79, 1.10-2.93), especially at higher prophylactic doses (2.29, 1.34-3.92).
      Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of
      58.5% (15.6-79.6) for households and from 68% (34.9-84.2) to 89% (67-97) in
      contacts of index cases. In influenza cases, compared with placebo the hazard
      ratios for time to alleviation of symptoms were 1.33, 1.29-1.37 for zanamivir;
      1.30, 1.13-1.50 for oseltamivir provided medication was started within 48 h of
      symptom onset. Viral nasal titres were significantly diminished by both drugs
      (weighted mean difference -0.62, -0.82 to -0.41). Oseltamivir at 150 mg daily was
      effective in preventing lower respiratory tract complications in influenza cases
      (OR 0.32, 0.18-0.57). We could find no credible data on the effects of
      oseltamivir on avian influenza. INTERPRETATION: The use of amantadine and
      rimantadine should be discouraged. Because of their low effectiveness,
      neuraminidase inhibitors should not be used in seasonal influenza control and
      should only be used in a serious epidemic or pandemic alongside other public
      health measures.

PMID- 16443038
TI  - Major epidemiological changes in sudden infant death syndrome: a 20-year
      population-based study in the UK.
AB  - BACKGROUND: Results of case-control studies in the past 5 years suggest that the
      epidemiology of sudden infant death syndrome (SIDS) has changed since the 1991 UK
      Back to Sleep campaign. The campaign's advice that parents put babies on their
      back to sleep led to a fall in death rates. We used a longitudinal dataset to
      assess these potential changes. METHODS: Population-based data from home visits
      have been collected for 369 consecutive unexpected infant deaths (300 SIDS and 69
      explained deaths) in Avon over 20 years (1984-2003). Data obtained between 1993
      and 1996 from 1300 controls with a chosen "reference" sleep before interview have
      been used for comparison. FINDINGS: Over the past 20 years, the proportion of
      children who died from SIDS while co-sleeping with their parents, has risen from
      12% to 50% (p<0.0001), but the actual number of SIDS deaths in the parental bed
      has halved (p=0.01). The proportion seems to have increased partly because the
      Back to Sleep campaign led to fewer deaths in infants sleeping alone-rather than
      because of a rise in deaths of infants who bed-shared, and partly because of an
      increase in the number of deaths in infants sleeping with their parents on a
      sofa. The proportion of deaths in families from deprived socioeconomic
      backgrounds has risen from 47% to 74% (p=0.003), the prevalence of maternal
      smoking during pregnancy from 57% to 86% (p=0.0004), and the proportion of pre
      term infants from 12% to 34% (p=0.0001). Although many SIDS infants come from
      large families, first-born infants are now the largest group. The age of infants
      who bed-share is significantly smaller than that before the campaign, and fewer
      are breastfed. INTERPRETATION: Factors that contribute to SIDS have changed in
      their importance over the past 20 years. Although the reasons for the rise in
      deaths when a parent sleeps with their infant on a sofa are still unclear, we
      strongly recommend that parents avoid this sleeping environment. Most SIDS deaths
      now occur in deprived families. To better understand contributory factors and
      plan preventive measures we need control data from similarly deprived families,
      and particularly, infant sleep environments.

PMID- 16443039
TI  - Fruit and vegetable consumption and stroke: meta-analysis of cohort studies.
AB  - BACKGROUND: Increased consumption of fruit and vegetables has been shown to be
      associated with a reduced risk of stroke in most epidemiological studies,
      although the extent of the association is uncertain. We quantitatively assessed
      the relation between fruit and vegetable intake and incidence of stroke in a meta
      analysis of cohort studies. METHODS: We searched MEDLINE, EMBASE, the Cochrane
      Library, and bibliographies of retrieved articles. Studies were included if they
      reported relative risks and corresponding 95% CIs of stroke with respect to
      frequency of fruit and vegetable intake. FINDINGS: Eight studies, consisting of
      nine independent cohorts, met the inclusion criteria. These groups included
      257,551 individuals (4917 stroke events) with an average follow-up of 13 years.
      Compared with individuals who had less than three servings of fruit and
      vegetables per day, the pooled relative risk of stroke was 0.89 (95% CI 0.83
      0.97) for those with three to five servings per day, and 0.74 (0.69-0.79) for
      those with more than five servings per day. Subgroup analyses showed that fruit
      and vegetables had a significant protective effect on both ischaemic and
      haemorrhagic stroke. INTERPRETATION: Increased fruit and vegetable intake in the
      range commonly consumed is associated with a reduced risk of stroke. Our results
      provide strong support for the recommendations to consume more than five servings
      of fruit and vegetables per day, which is likely to cause a major reduction in
      strokes.

PMID- 16443040
TI  - Equity in use of home-based or facility-based skilled obstetric care in rural
      Bangladesh: an observational study.
AB  - BACKGROUND: Few studies have assessed whether the poorest people in developing
      countries benefit from giving birth at home rather than in a facility. We
      analysed whether socioeconomic status results in differences in the use of
      professional midwives at home and in a basic obstetric facility in a rural area
      of Bangladesh, where obstetric care was free of charge. METHODS: We routinely
      obtained data from Matlab, Bangladesh between 1987 and 2001. We compared the
      benefits of home-based and facility-based obstetric care using a multinomial
      logistic and binomial log link regression, controlling for multiple confounders.
      FINDINGS: Whether or not a midwife was used at home or in a facility differed
      significantly with wealth (adjusted odds ratio comparing the wealthiest and
      poorest quintiles 1.94 [95% CI 1.69-2.24] for home-based care, and 2.05 [1.72
      2.43] for facility-based care). The gap between rich and poor widened after the
      introduction of facility-based care in 1996. The risk ratio (RR) between the
      wealthiest and poorest quintiles was 1.91 (adjusted RR 1.49 [95% CI 1.16-1.91]
      when most births with a midwife took place at home compared with 2.71 (1.66 [1.41
      1.96]) at the peak of facility-based care. INTERPRETATION: In this area of
      Bangladesh, a shift from home-based to facility-based basic obstetric care is
      feasible but might lead to increased inequities in access to health care.
      However, there is also evidence of substantial inequities in home births. Before
      developing countries reinforce home-based births with a skilled attendant,
      research is needed to compare the feasibility, cost, effectiveness,
      acceptability, and implications for health-care equity in both approaches.

PMID- 16443041
TI  - Kidney stones: pathophysiology and medical management.
AB  - The formation of stones in the urinary tract stems from a wide range of
      underlying disorders. That clinicians look for the underlying causes for
      nephrolithiasis is imperative to direct management. There are many advances in
      genetics, pathophysiology, diagnostic imaging, medical treatment, medical
      prevention, and surgical intervention of nephrolithiasis. Here, I provide a brief
      general background and focus mainly on pathophysiology and medical treatment of
      kidney stones. Although important advances have been made in understanding
      nephrolithiasis from single gene defects, the understanding of polygenetic causes
      of kidney stones is still largely elusive. A substantial proportion of data that
      resulted in new methods of treatment and prevention, which can be empirical or
      definitive, has focused on urinary luminal chemical composition of the
      precipitating solutes. Manipulation of inhibitors and epithelial factors is
      important and needs further investigation. Advances in the management of
      nephrolithiasis depend on combined efforts of clinicians and scientists to
      understand the pathophysiology.

PMID- 16443042
TI  - Passage from India.

PMID- 16443043
TI  - Chronic fatigue syndrome.
AB  - During the past two decades, there has been heated debate about chronic fatigue
      syndrome (CFS) among researchers, practitioners, and patients. Few illnesses have
      been discussed so extensively. The existence of the disorder has been questioned,
      its underlying pathophysiology debated, and an effective treatment opposed;
      patients' organisations have participated in scientific discussions. In this
      review, we look back on several controversies over CFS with respect to its
      definition, diagnosis, pathophysiology, and treatment. We review issues of
      epidemiology and clinical manifestations, focusing on the scientific status of
      CFS. Modern neuroscience and genetics research offer interesting findings for new
      hypotheses on the aetiology and pathogenesis of the illness. We also discuss
      promising future issues, such as psychopathophysiology and mechanisms of
      improvement, and suggest multidisciplinary prospective studies of CFS and fatigue
      in the general population. These studies should pay particular attention to
      similarities to and differences from functional somatic syndromes and other
      fatiguing conditions.

PMID- 16443044
TI  - Controversies in ventricular remodelling.
AB  - Ventricular remodelling describes structural changes in the left ventricle in
      response to chronic alterations in loading conditions, with three major patterns:
      concentric remodelling, when a pressure load leads to growth in cardiomyocyte
      thickness; eccentric hypertrophy, when a volume load produces myocyte
      lengthening; and myocardial infarction, an amalgam of patterns in which stretched
      and dilated infarcted tissue increases left-ventricular volume with a combined
      volume and pressure load on non-infarcted areas. Whether left-ventricular
      hypertrophy is adaptive or maladaptive is controversial, as suggested by patterns
      of signalling pathways, transgenic models, and clinical findings in aortic
      stenosis. The transition from apparently compensated hypertrophy to the failing
      heart indicates a changing balance between metalloproteinases and their
      inhibitors, effects of reactive oxygen species, and death-promoting and
      profibrotic neurohumoral responses. These processes are evasive therapeutic
      targets. Here, we discuss potential novel therapies for these disorders,
      including: sildenafil, an unexpected option for anti-transition therapy; surgery
      for increased sphericity caused by chronic volume overload of mitral
      regurgitation; an antifibrotic peptide to inhibit the fibrogenic effects of
      transforming growth factor beta; mechanical intervention in advanced heart
      failure; and stem-cell therapy.

PMID- 16443045
TI  - Confusion, memory disorders, and ophthalmoparesis in a patient with AIDS.

PMID- 16443047
TI  - Targeting VEGF in cancer therapy.

PMID- 16443048
TI  - Cutaneous malignancy and human immunodeficiency virus disease.
AB  - Certain skin cancers occur with increased frequency or altered course in patients
      infected with HIV. Malignant melanoma and squamous cell carcinoma are examples of
      cutaneous malignancies that have a more aggressive course in patients with HIV.
      Others, such as basal cell carcinoma, appear more frequently in this population
      but do not appear to be more aggressive. The incidence of HIV-associated
      Kapsosi's sarcoma has markedly decreased since the advent of HIV antiretroviral
      therapy. Our understanding of the pathogenesis of this malignancy and its unique
      management issues are fully reviewed. Cutaneous T-cell lymphoma (CTCL) is rare in
      this population. Other types of cutaneous lymphoma and HIV-associated pseudo-CTCL
      are discussed. This article addresses prevention, treatment, and follow-up
      strategies for this at-risk population. LEARNING OBJECTIVE: At the completion of
      this learning activity, participants should be familiar with the unique
      epidemiology, clinical course, and management of cutaneous malignancy in patients
      infected with HIV.

PMID- 16443049
TI  - Challenges facing academic dermatology: survey data on the faculty workforce.
AB  - BACKGROUND: There is a perception among many academic dermatologists that
      departments of dermatology face severe challenges with recruitment and retention
      of faculty. In an era when evidence points to a shortage of dermatologists and
      residency graduates have plentiful private practice offers in almost every
      geographic area, some fear that academic programs will face even steeper
      challenges attracting and keeping enough dermatologists on staff. METHODS: To
      compare the practice patterns of academic dermatologists with those of the
      dermatology workforce in other settings, data from the American Academy of
      Dermatology 2002 Practice Profile Survey were analyzed (1425 respondents, 35%
      response rate). RESULTS: The mean age of academic dermatologists (45.6 years) was
      younger than that of those in other practice settings (51.9 years solo practice,
      49.0 years multispecialty group), and older age cohorts were significantly less
      likely to be working in academics (P < .001). Academic physicians were much more
      likely than those in solo practice or dermatology-only groups (62.2% vs 18.3%
      39.4%) to report that their institution or practice was seeking new
      dermatologists. The average waiting time for new patient appointments varied from
      a low of 31.1 days in solo practices to a high of 55.9 days in academic
      practices. Academic dermatologists saw 32% to 41% fewer patients per week, but
      spent much more time (24.1 vs 5.5-8.6 h/wk) participating in research, hospital
      consults, medical writing, administrative activities, and teaching than
      dermatologists in any other setting. LIMITATIONS: Academic dermatologists
      reflected a relatively small proportion of survey respondents, and may not be
      representative of the nation's dermatology faculty (although the percentage of
      academics in the survey was similar to that in the overall workforce). Possible
      response biases could also have affected the survey results. CONCLUSIONS: The
      survey results identify a number of differences between the practice patterns of
      academic dermatologists and their colleagues in other settings, and suggest that
      academic departments of dermatology may be facing unique workforce challenges.

PMID- 16443050
TI  - Cutaneous symptoms of dermatomyositis significantly impact patients' quality of
      life.
AB  - BACKGROUND: Dermatomyositis affects visible skin and causes disease symptoms that
      can affect patients' quality of life (QOL). METHODS: In all, 71 patients with
      dermatomyositis or dermatomyositis sine myositis completed two QOL measures (the
      Skindex-16 and the Dermatology Life Quality Index) and a visual analog scale for
      pruritus. Disease severity was assessed by Physician's Global Assessment.
      RESULTS: The mean Dermatology Life Quality Index score was 10.7 and the mean
      Skindex-16 score was 51.1. Itching contributed to impact on both the Dermatology
      Life Quality Index and Skindex-16. Females reported worse QOL. LIMITATIONS: The
      effect of treatment on quality of life was not assessed in these analyses.
      CONCLUSION: QOL impairment in dermatomyositis is greater than in other skin
      conditions including psoriasis and atopic dermatitis. Pruritus is an important
      treatable factor that significantly impacts QOL for patients with
      dermatomyositis.

PMID- 16443051
TI  - Dermatomyositis associated with malignant melanoma--a marker of poor prognosis?
AB  - BACKGROUND: Dermatomyositis (DM) is an inflammatory connective tissue disorder
      well recognized as a paraneoplastic syndrome in adults. OBJECTIVE: The objective
      of this study was to assess the prognosis of DM associated with malignant
      melanoma (MM). PATIENTS AND METHODS: We systematically searched databases
      (PubMed, MEDLINE, and WEB OF SCIENCE) for articles reporting the concurrence of
      DM and MM. For the literature study, time of onset of DM in relation to diagnosis
      of MM (before, concomitant with, or after), stage of MM after restaging
      (according to the American Joint Committee on Cancer [AJCC] guidelines, 2001),
      and survival time after diagnosis of DM were recorded. Survival time studies and
      univariate statistical analyses were performed. Furthermore, we present our own
      clinical case of a patient with DM concomitantly occurring with regional lymph
      node metastasis of MM. RESULTS: In 5 cases DM occurred before, in 6 cases
      concomitantly with, and in 6 cases after progression of MM. Univariate analysis
      identified the AJCC stage of MM as a significant prognostic factor. Gender, age,
      and the time interval between onset of DM and progression of melanoma were
      unrelated. The 1-year actuarial survival rate was 0% for patients with DM when
      occurring with MM at stage IV and 60% when occurring with MM at stage III (P <
      .05). The estimated mean survival time was 6.6 months for patients with MM stage
      IV and 57 months for stage III. LIMITATIONS: The conclusions from this study are
      limited by the relatively small number of articles that reported the association
      of MM and DM. CONCLUSION: DM occurring in patients with MM at stage IV is
      connected with an extremely poor prognosis, whereas the few reported patients
      with DM and MM at stage III, including our case, have a prognosis similar to
      stage III patients without DM.

PMID- 16443052
TI  - Clinical and serological characteristics of progressive facial hemiatrophy: a
      case series of 12 patients.
AB  - BACKGROUND: Progressive facial hemiatrophy (PFH) is characterized by a slowly
      progressive atrophy of soft tissues and in some cases bony structures. Coexisting
      features of localized scleroderma (LS) are commonly observed, indicating the
      close nature of both disorders. OBJECTIVE: We sought to investigate clinical,
      serological, and radiographic findings in PFH from 278 patients with LS and to
      discuss the relationship to linear scleroderma en coup de sabre (LSCS). METHOD: A
      total of 12 patients with PFH were retrospectively evaluated on the basis of
      clinical, serological, and radiographic findings. RESULTS: Five patients (42%)
      presented with complete PFH, and 7 patients (58%) with partial PFH involving
      either cheek or forehead. Five of the patients (42%) had a coexisting LSCS
      lesion, and 3 of them (25%) had concomitant LS of the trunk. Intraoral
      involvement was present in 6 cases. Neurological involvement was common, in
      particular, epileptic seizures. Serologic investigations showed neither evidence
      for infection with Borrelia burgdorferi nor any other indication of underlying
      systemic immunological disorders. LIMITATIONS: There were a relatively small
      number of patients in a retrospective study. CONCLUSION: The reported cases
      suggest a close relationship between PFH and LSCS. PFH might appear as two
      different subtypes, one involving cutaneous structures and presenting with
      clinical features similar to LSCS, one being strictly restricted to subcutaneous
      structures, primarily affecting the cheek area. The manifold clinical features of
      central nervous system involvement indicate the pathogenetic importance of
      neurological involvement in the development of PFH. Magnetic resonance imaging
      should be included in the tools of standard diagnostic procedures in patients
      with PFH. The etiologic relevance of autoimmunity as well as preceding trauma
      should be investigated in larger collective studies.

PMID- 16443054
TI  - Adapalene gel 0.3% for the treatment of acne vulgaris: a multicenter, randomized,
      double-blind, controlled, phase III trial.
AB  - BACKGROUND: A new 0.3% gel formulation of adapalene has been developed.
      OBJECTIVE: We sought to provide evidence of the superiority of adapalene gel 0.3%
      over adapalene gel 0.1% and gel vehicle in the treatment of acne. METHODS: A
      total of 653 patients were randomized to receive adapalene gel 0.3%, adapalene
      gel 0.1%, or vehicle once daily for 12 weeks (2:2:1 randomization). Analysis for
      efficacy was conducted on correlated repeated measurements at weeks 8 and 12
      using Generalized Estimating Equation methodology. RESULTS: Adapalene gel 0.3%
      was significantly superior to adapalene gel 0.1% and vehicle in success rate,
      total lesion count, and inflammatory lesion count. A consistent, dose-dependent
      effect was demonstrated for all efficacy measures. Signs and symptoms were mostly
      mild to moderate and transient in nature. LIMITATIONS: Adjunctive topical or oral
      agents and their impact on acne were not studied in this trial. CONCLUSIONS:
      Adapalene gel 0.3% was effective and well tolerated in the treatment of acne.

PMID- 16443053
TI  - Low plasma coenzyme Q10 levels as an independent prognostic factor for melanoma
      progression.
AB  - BACKGROUND: Abnormally low plasma levels of coenzyme Q10 (CoQ10) have been found
      in patients with cancer of the breast, lung, or pancreas. OBJECTIVE: A
      prospective study of patients with melanoma was conducted to assess the
      usefulness of CoQ10 plasma levels in predicting the risk of metastasis and the
      duration of the metastasis-free interval. METHODS: Between January 1997 and
      August 2004, plasma CoQ10 levels were measured with high-performance liquid
      chromatography in 117 consecutive melanoma patients without clinical or
      instrumental evidence of metastasis according to American Joint Committee on
      Cancer criteria and in 125 matched volunteers without clinically suspect
      pigmented lesions. Patients taking CoQ10 or cholesterol-lowering medications and
      those with a diagnosis of diabetes mellitus were excluded from the study.
      Multiple statistical methods were used to evaluate differences between patients
      and control subjects and between patients who did (32.5%) and did not (67.5%)
      develop metastases during follow-up. RESULTS: CoQ10 levels were significantly
      lower in patients than in control subjects (t test: P < .0001) and in patients
      who developed metastases than in the metastasis-free subgroup (t test: P <
      .0001). Logistic regression analysis indicated that plasma CoQ10 levels were a
      significant predictor of metastasis (P = .0013). The odds ratio for metastatic
      disease in patients with CoQ10 levels that were less than 0.6 mg/L (the low-end
      value of the range measured in a normal population) was 7.9, and the metastasis
      free interval was almost double in patients with CoQ10 levels 0.6 mg/L or higher
      (Kaplan-Meier analysis: P < .001). LIMITATIONS: A study with a larger sample,
      which is currently being recruited, and a longer follow-up will doubtlessly
      increase the statistical power and enable survival statistics to be obtained.
      CONCLUSIONS: Analysis of our findings suggests that baseline plasma CoQ10 levels
      are a powerful and independent prognostic factor that can be used to estimate the
      risk for melanoma progression.

PMID- 16443055
TI  - Cutaneous tissue angiotensin-converting enzyme may participate in pathologic scar
      formation in human skin.
AB  - BACKGROUND: Many studies have shown that up-regulation of angiotensin-converting
      enzyme (ACE) participates in adverse fibrous remodeling. Although this has become
      an accepted fact in the cardiovascular field, the relationship between ACE and
      cutaneous fibrous remodeling, such as keloid or hypertrophic scars, remains
      unknown. OBJECTIVE: We sought to investigate ACE in normal skin, wounded skin,
      and pathologic scars. METHODS: Ten samples undergoing a normal wound-healing
      process, 14 samples of pathologic scar tissue, and 15 samples of normal skin were
      used in this study. Cutaneous tissue ACE activities were measured with high
      pressure liquid chromatography. Localization of ACE was assessed by
      immunohistochemistry. RESULTS: The ACE activity in pathologic scar tissue was
      significantly higher than in normal and wounded skin. Immunohistochemical studies
      demonstrated that myofibroblasts were stained with anti-ACE antibody.
      LIMITATIONS: The study is small. CONCLUSIONS: These results suggest that up
      regulated ACE may participate in cutaneous pathologic scar formation the same as
      the cardiovascular system.

PMID- 16443056
TI  - Tetracyclines: nonantibiotic properties and their clinical implications.
AB  - Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal
      level where they interfere with protein synthesis. They were first widely
      prescribed by dermatologists in the early 1950s when it was discovered that they
      were effective as a treatment for acne. More recently, biologic actions affecting
      inflammation, proteolysis, angiogenesis, apoptosis, metal chelation,
      ionophoresis, and bone metabolism have been researched. The therapeutic effects
      of tetracycline and its analogues in various diseases have also been
      investigated. These include rosacea, bullous dermatoses, neutrophilic diseases,
      pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis,
      periodontitis, and autoimmune disorders such as rheumatoid arthritis and
      scleroderma. We review the nonantibiotic properties of tetracycline and its
      analogues and their potential for clinical application.

PMID- 16443057
TI  - Concomitant treatment of psoriasis of the hands and feet with pulsed dye laser
      and topical calcipotriol, salicylic acid, or both: a prospective open study in 41
      patients.
AB  - BACKGROUND: Psoriasis of the hands and feet is a chronic disease which is often
      resistant to the usual topical therapies. It has considerable morbidity and
      seriously affects the quality of life of patients. OBJECTIVE: We sought to
      prospectively evaluate the efficacy and safety of pulsed dye laser (PDL)
      treatment of psoriasis of the hands and feet. METHODS: In all, 41 patients with
      therapy-resistant psoriasis of the hands and feet were treated once every 4 to 6
      weeks with PDL at 585-nm wavelength, 450-microsecond pulse duration, 7-mm spot
      diameter, and 5- to 6.5-J/cm2 fluence. Calcipotriol ointment and salicylic acid
      5% to 10% ointment were used as keratolytic agents. Treatment efficacy was
      evaluated by blinded comparison of photographs of the lesions taken before and
      after PDL treatment in each patient. RESULTS: A good to very good improvement in
      the lesions was observed in 76% of the patients after treatment. An average
      duration of remission was 11 months. Side effects were transient purpura,
      moderate discomfort during the treatment, transient hyperpigmentation or
      hypopigmentation, and incidental transient crustae. LIMITATIONS: This was an open
      prospective study with a limited number of patients who were concomitantly
      treated with calcipotriol and salicylic acid ointment. Patients with
      photointolerance, on medication with phototoxic or photoallergic drugs, and with
      widespread psoriasis were excluded. CONCLUSIONS: Concomitant treatment with PDL
      and topical calcipotriol, salicylic acid, or both was a satisfactory modality for
      treating psoriasis of the hands and feet. There was a subjective improvement in
      the symptoms and quality of life in all patients.

PMID- 16443059
TI  - The 800-nm diode laser in the treatment of leg veins: assessment at 6 months.
AB  - BACKGROUND: The efficacy of the 800-nm diode laser system in clearing leg veins
      was analyzed subjectively and objectively in a variety of leg veins. METHODS: A
      total of 10 women (age 25-55 years, skin types II-IV) with a variety of leg vein
      types were treated with an 800-nm diode laser. A sequence of pulses (5-8 stacked
      pulses, pulse duration 50 milliseconds, delay 50 milliseconds) was applied on a 3
      mm spot (210-336 J/cm2 fluence, depending on vessel size). Treatment on the same
      vein was performed at intervals of 2 months until complete clearance was achieved
      (maximum: 3 treatments). The results were assessed at 6 months from the last
      treatment. Patients evaluated their subjective improvement by means of a
      questionnaire to elicit the satisfaction index. In an independent objective
      assessment, the clearance index was based on the pretreatment and posttreatment
      clinical photography, also analyzed by a computer program. RESULTS: All patients
      completed the trial with mild but transient side effects. The patient 6-month
      assessments for very good, good, fair, poor, and worse were 1, 5, 3, 1, and 0,
      respectively. For the clinician-assessed clearance index, the numbers for the
      same grades were 2, 6, 2, 0, and 0, and for the computer assessment they were 1,
      6, 2, 1, and 0. No patient scored worse in any assessment. The overall
      satisfaction index and clinician and computer clearance indexes were 60%, 80%,
      and 70%, respectively. LIMITATIONS: No control group could be obtained in this
      study. CONCLUSIONS: The 800-nm diode laser as used in the study may well offer an
      effective treatment method for leg veins that is comparatively pain and side
      effect free. Best results were obtained in vessels of 3 to 4 mm in diameter
      located on the thigh, and in patients with phototype III skin. No correlation was
      seen between results and patient age.

PMID- 16443058
TI  - A quality rating scale for aesthetic surgical procedures.
AB  - BACKGROUND: Cosmetic dermatologic procedures offer the promise of visible
      aesthetic enhancement with minimal risk. While in recent years the number of
      available procedures has proliferated, there are few objective methods for
      evaluating the relative quality of these procedures for particular indications or
      specific patients. OBJECTIVE: (A) To develop a simple, easy-to-use numerical
      rating scale to assess the quality of cosmetic surgical procedures on a range of
      parameters pertaining to clinical efficacy and patient satisfaction; (B) to
      statistically validate the discriminative value of this rating scale. METHODS:
      (A) Patient and physician interviews were performed to elicit a list of factors
      that may collectively characterize the clinical efficacy and patient tolerability
      of cosmetic dermatologic procedures. A 0-100 point rating scale was developed
      based on these factors, with the face-validity of this scale checked by a group
      of patients and physicians; (B) Statistical analysis of the questionnaire was
      performed by asking 15 expert cosmetic dermatologic surgeons to use it to rate 23
      common cosmetic dermatologic procedures, and analyzing the results. RESULTS: (A)
      An easy-to-use scale was constructed to assess the quality of cosmetic
      dermatologic procedures by rating the associated cost, risk, time (procedure and
      recovery), discomfort, results, and longevity of benefit. A "physician adjustment
      factor" was used to further increase the relevance of this 0-100 point scale for
      specific patients; (B) Repeated-measures analysis of variations (ANOVAs)
      performed on the data from the survey of experts demonstrated that this scale can
      be used to discriminate between common dermatologic procedures. The differences
      in mean subscores and total scores among procedures grouped by anatomic site and
      target lesion-type were significant at the level of P < .05. LIMITATIONS: Patient
      preferences exogenous to the rating scale may increase or decrease the
      suitability of specific procedures. CONCLUSIONS: Common cosmetic dermatologic
      procedures are of uniformly high quality, as per expert ratings on a systematic
      measure. This quality rating scale appears statistically valid and robust, given
      that expert raters assigned similar ratings to the same procedures but mean
      ratings were different across procedures. In the future, this quality rating
      scale can be used to assess novel interventions, and to help dermatologic
      surgeons faced with patient concern to optimally select among alternative
      procedures for a given indication.

PMID- 16443060
TI  - Clinicopathologic features of skin cancer in organ transplant recipients: a
      retrospective case-control series.
AB  - BACKGROUND: Non-melanoma skin cancers (NMSCs) are increased in organ transplant
      recipients, but transplant and immunocompetent squamous and basal cell carcinomas
      (SCCs, BCCs) have not been compared previously in a single-center study.
      OBJECTIVE: To compare clinicopathologic features of transplant and
      immunocompetent NMSCs. METHODS: Consecutive transplant NMSCs (60 SCCs, 100 BCCs)
      and immunocompetent NMSCs (40 SCCs, 125 BCCs) presenting between 1995-1997.
      RESULTS: Transplant patients were 15 years younger at time of NMSC diagnosis
      compared with immunocompetent individuals, and transplant tumors were often more
      multiple and extracephalic. Spindle cell morphology was more common in transplant
      SCCs, a superficial component was more common in transplant BCCs, and histologic
      features of HPV infection were overrepresented in transplant tumors. Outcome was
      worse for transplant SCCs but not transplant BCCs. LIMITATIONS: Histologic
      features required to identify HPV infection have not been validated. CONCLUSIONS:
      These findings have direct implications for clinical care. The increased
      frequency and distribution of transplant NMSCs underscore the importance of whole
      body surveillance. Transplant SCCs, particularly those with diffuse spindle cell
      change, may require more aggressive management, whereas transplant BCCs do not.
      Finally, our data support differences in the pathogenesis of transplant NMSC,
      which may influence future preventive and therapeutic strategies.

PMID- 16443061
TI  - The vitamin D questions: how much do you need and how should you get it?
AB  - UV radiation is a well-documented human carcinogen, indisputably linked to the
      current continued increased rate of skin cancer. UV radiation is also responsible
      for cutaneous synthesis of vitamin (vit) D3, a substance that is then
      sequentially hydroxylated in the liver and kidney to yield 1,25(OH)2 vit D, a
      hormone critical for calcium homeostasis and skeletal maintenance. Because the UV
      action spectra for DNA damage leading to skin cancer and for vit D photosynthesis
      are virtually identical, the harmful and beneficial effects of UV irradiation are
      inseparable. This has given rise to the argument that sun avoidance, with a goal
      of skin cancer prevention, may compromise vit D sufficiency. Public interest in
      this matter has been heightened in recent years by multiple studies correlating
      the level of 25-OH vit D, the readily measurable "storage" precursor form of the
      vit, with a variety of benefits separate from skeletal health. Although the
      studies are of variable quality and all alleged treatment benefits are based on
      dietary supplementation with vit D, not on increased sun exposure, they have been
      interpreted by some as support for advocating increased sun exposure of the
      public at large. The goal of this review is to provide a detailed, balanced, and
      referenced discussion of the complex literature underlying the current popular
      interest in vit D and sun exposure for the purpose of increasing vit D
      photosynthesis. We review the nomenclature, metabolism, and established functions
      of vit D; the evidence supporting the less well-established but purported vit D
      effects; the concept of vit D insufficiency; populations at risk for vit D
      deficiency; and finally the risk/benefit of obtaining vit D from cutaneous
      photosynthesis versus diet or supplementation.

PMID- 16443062
TI  - A recurrent rash with fever and arthropathy.

PMID- 16443063
TI  - The history of syphilis.

PMID- 16443064
TI  - Syphilis and the city.

PMID- 16443065
TI  - Maybe it was a cutaneous horn....

PMID- 16443066
TI  - Surgical pearl: evacuation of milia with a paper clip.

PMID- 16443067
TI  - Medical pearl: dermatitis herpetiformis--potential for confusion with eczema.

PMID- 16443068
TI  - Rising educational debt levels in recent dermatology trainees and effects on
      career choices.
AB  - BACKGROUND: Educational debt levels are outpacing inflation. OBJECTIVE: To
      determine whether debt levels influence career choices of graduating dermatology
      residents. METHODS: Anonymous surveys of graduating dermatology residents.
      RESULTS: The presence of debt was associated negatively with pursuing fellowship
      training in 1999 and 2004 (P < .05) but did not affect choices about entering
      solo practice or job dissatisfaction levels. LIMITATIONS: This study relies on
      self-reported data, and some surveys were incomplete. CONCLUSION: Debt levels do
      not appear to significantly influence the career choices of dermatology
      residents.

PMID- 16443069
TI  - Socioeconomic status influences care of patients with acne in Ontario, Canada.
AB  - BACKGROUND: Canada's universal health care system is designed to ensure equitable
      access to medical care based on need rather than socioeconomic status, although a
      number of studies indicate a preferential access and greater use of specialist
      services for those patients in higher socioeconomic groups. OBJECTIVES: The
      primary objective of this study was to determine whether socioeconomic status
      influences access to specialist care by a dermatologist for the management of
      acne in Ontario, Canada. A secondary objective was to determine whether the urban
      rural dwelling status of patients affects access to specialty care. METHODS: We
      conducted a population-based cohort study using administrative health care
      databases covering more than 12 million residents of Ontario. Individuals age 12
      to 27 years with a new diagnosis of acne by a general practitioner were
      identified as belonging to 1 of 5 socioeconomic groups based on median annual
      neighborhood household income. Patients were then observed for 2 years after the
      index visit to identify visits to a dermatologist. The main outcome measure was
      visitation to a dermatologist within 2 years of an initial diagnosis of acne.
      RESULTS: The study cohort consisted of 295,469 patients given a diagnosis of acne
      by their primary care physician of which 59,799 (20%) were subsequently referred
      to a dermatologist. Of those in the lowest income group of less than Can dollars
      20,000, 17% were referred to a dermatologist, as compared with 24% in the highest
      income group of greater than Can dollars 80,000 (P value for trend < .001).
      Furthermore, patients living in an urban area had a 43% greater likelihood of
      being referred to a dermatologist (odds ratio 1.43, 95% confidence interval 1.39
      1.48) as compared with patients in a rural location. LIMITATIONS: Limitations of
      our study include imputing socioeconomic status of patients on the basis of
      median income at the neighborhood level rather than on the basis of data on
      individual patients. Furthermore, our use of administrative databases did not
      allow us to characterize the severity of acne in our population cohort and
      whether that would affect referral patterns. CONCLUSION: Within Canada's
      universal health care system, those likely to be in lower socioeconomic groups
      are significantly less likely to visit a dermatologist for specialist
      consultation.

PMID- 16443070
TI  - Cheilitis glandularis: a clinical marker for both malignancy and/or severe
      inflammatory disease of the oral cavity.
AB  - We report the case of an 84-year-old white male who underwent vermilionectomy for
      removal of a tumor, which proved to be squamous cell carcinoma. Chelitis
      glandularis related to marked actinic damage was noted at a subsequent visit. The
      presence of chelitis glandularis should be investigated for the presence of
      neoplasia, immunosuppression, or inflammatory diseases related to extremely poor
      oral hygiene.

PMID- 16443071
TI  - Clinical and dermatoscopic fading of post-transplant eruptive melanocytic nevi
      after suspension of immunosuppressive therapy.
AB  - Excess melanocytic nevi have been reported in several groups of immunosuppressed
      patients, including organ transplant recipients. We report the case of a 16-year
      old transplant recipient whose post-transplant melanocytic nevi decreased in size
      and color after graft rejection and interruption of immunosuppressive therapy.
      This case may represent a visual example of an effective immunosurveillance
      system against melanocytic nevi.

PMID- 16443072
TI  - Dermoscopy for "true" amelanotic melanoma: a clinical dermoscopic-pathologic case
      study.
AB  - Completely amelanotic melanomas are rare and therefore often misclassified, with
      tragic consequences for patients. The use of dermoscopy for these lesions has not
      been validated yet because of the lack of studies that are based on large series.
      The analysis of the vascular pattern, which is often the only dermoscopic
      parameter to be seen, is therefore essential for a correct diagnosis. We present
      a case of "true" amelanotic melanoma on the forehead of an 89-year-old man, which
      clinically mimicked squamous cell carcinoma. The patient was investigated both
      clinically and by focusing on his dermoscopic features and their pathologic
      correlates. The dermoscopic diagnostic algorithms routinely used for pigmented
      lesions are not helpful in diagnosing amelanotic melanoma because they are based
      on specific parameters not normally seen in amelanotic lesions. In the light of
      our experience, pattern analysis is the most reliable method for diagnosing these
      particular lesions correctly because it allows in-depth morphologic analysis of
      the few parameters found.

PMID- 16443073
TI  - Metastatic glucagonoma: treatment with liver transplantation.
AB  - Glucagonoma is a rare pancreatic endocrine tumor that is often both well
      developed and malignant at detection. In the case of metastatic spread the
      patient has a poor long-term prognosis. We hope to familiarize dermatologists and
      other specialists with this rare and potentially fatal disorder because early
      recognition of necrolytic migratory erythema, a clinical feature that may appear
      in patients with glucagonoma, can lead to possible cure, whereas delayed
      identification of the disease is associated with metastatic disease and a poor
      prognosis. We report the case of a 57-year-old patient with a metastatic glucagon
      producing tumor; necrolytic migratory erythema was diagnosed and was successfully
      treated by a multimodal intervention including liver transplantation. Currently,
      72 months after transplantation, our patient is in complete remission, which has
      been verified by somatostatin receptor scintigraphy monitoring, computed
      tomographic scanning and glucagon serum control. Increased awareness of the
      clinical symptoms and visible polymorphic mucocutaneous and nonspecific
      histopathologic features of glucagonoma syndrome is needed to avoid unnecessary
      delay in the diagnosis of this syndrome.

PMID- 16443074
TI  - Infantile midline facial hemangioma with agenesis of the corpus callosum and
      sinus pericranii: another face of the PHACE syndrome.
AB  - BACKGROUND: In the majority of cases, infantile hemangiomas are not associated
      with any other abnormalities. Occasionally, they may indicate the presence of
      systemic malformations. PHACE syndrome includes the coexistence of hemangioma,
      posterior fossa brain abnormalities, arterial anomalies, coarctation of the
      aorta, cardiac defects, and eye abnormalities. We report a case of a 2-month-old
      female with PHACE syndrome who also had sinus pericranii. CLINICAL CASE: A 2
      month-old girl was seen for a plaque-like, segmental, midfacial hemangioma, with
      recurrent hemorrhages, noted at birth. As part of the PHACE syndrome, she had a
      midline facial hemangioma, absent corpus callosum, hypoplastic internal carotid
      artery, and an abnormal tortuous dysplastic basilar artery. Digital subtraction
      angiography showed sinus pericranii. The patient underwent successful
      endovascular embolization of the hemangioma that prevented further bleeding.
      CONCLUSION: Sinus pericranii is a rare finding that has not, to our knowledge,
      been previously associated with PHACE syndrome. Central nervous system, not only
      posterior fossa, abnormalities are frequently encountered in PHACE syndrome.
      Endovascular embolization of the facial hemangioma in our patient was a useful
      therapy.

PMID- 16443075
TI  - The dark side of photomicrographs in pathology reports: liability and practical
      concerns hidden from view.
AB  - The rapid evolution of digital imaging has facilitated the ability to include
      photomicrographs in pathology reports. Although these pictures may seem to be an
      informative accompaniment to the written report, there are many problems raised
      by the images, which are not generally recognized. These include lack of quality
      standards, selection of representative images, and liability implications, which
      are addressed by well-established legal precedent. For dermatologists there is no
      such thing as a casual interest in a photomicrograph on a report, for it acts to
      distribute a share of liability by obligating the clinician to interpret the
      image properly. The risk management ramifications of these unintended
      consequences should be strongly considered by clinicians who favor the receipt of
      photomicrographic images in their pathology reports.

PMID- 16443076
TI  - Trichoblastoma with a dilated pore.

PMID- 16443077
TI  - An acneiform eruption due to erlotinib: prognostic implications and management.

PMID- 16443078
TI  - Subcutaneous sarcoidosis presenting after treatment of Cushing's disease.

PMID- 16443079
TI  - Etanercept monotherapy for a patient with psoriasis, psoriatic arthritis, and
      concomitant hepatitis C infection.

PMID- 16443080
TI  - Marked and restricted cutaneous pigmentation induced by selective intra-arterial
      cisplatin infusion.

PMID- 16443081
TI  - Cutaneous metastases as the first manifestation of pleural malignant
      mesothelioma.

PMID- 16443082
TI  - Priority claims for surgical techniques.

PMID- 16443083
TI  - The adequate supply of dermatologists in Arkansas.

PMID- 16443084
TI  - More than one melanoma in situ of the penis.

PMID- 16443085
TI  - Risk factors for ICU-acquired methicillin-resistant Staphylococcus aureus
      infections.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major
      nosocomial pathogen that causes severe morbidity and mortality in many hospitals
      worldwide, and MRSA infections are frequent in intensive care units (ICUs).
      OBJECTIVE: A prospective study was implemented to investigate the risk factors
      for ICU-acquired MRSA infections. METHODS: This study was conducted in surgical
      and neurologic ICUs from May to November 2003. The patients staying in ICUs more
      than 48 hours were included in the study. All of the patients were visited daily,
      and data were recorded on individual forms for each patient until discharge or
      death. Nasal swab cultures were done within 48 hours of ICU admission and
      repeated every week until the patients colonized with MRSA or were discharged
      from ICUs. ICU-acquired MRSA infection was diagnosed when MRSA was isolated from
      the infected site. RESULTS: Overall, 249 patients were followed during the study.
      MRSA infection was detected in 21 (8.4%) of these patients. The most frequent
      infection was primary bloodstream infection (10/21, 47%). It was followed by
      pneumonia (8/21, 38%) and surgical site infection (3/21, 14%). Nasal MRSA
      colonization was detected in 59 (23.7%) patients, and 12 of them (20.3%)
      developed MRSA infection. In univariate analysis, hospitalization period in an
      ICU, intraabdominal and orthopedic pathologies, mechanical ventilation, central
      venous catheter insertion, total parenteral nutrition, previous antibiotic use,
      surgical ICU stay, nasal MRSA colonization, and presence of more than 2 patients
      having nasal colonization in the same ICU at the same time were found significant
      for MRSA infections. In multivariate analysis; hospitalization period in an ICU
      (OR, 1.090; 95% CI: 1.038-1.144, P = .001), central venous catheter insertion
      (OR, 1.822; 95% CI: 1.095-3.033, P = .021), previous antibiotic use (OR, 2.337;
      95% CI: 1.326-4.119, P = .003) and presence of more than 2 patients having nasal
      colonization in the same ICU at the same time (OR, 1.398; 95% CI: 1.020-1.917, P
      = .037) were independently associated with MRSA infections. CONCLUSION: According
      to the our results, hospitalization period in an ICU, presence of patients
      colonized with MRSA in the same ICU at the same time, previous antibiotic use,
      and central venous catheter insertion are independent risk factors for ICU
      acquired MRSA infections. Detection of these factors helps to decrease the rate
      of MRSA infections in the ICUs.

PMID- 16443086
TI  - Decrease in the incidence of mupirocin resistance among methicillin-resistant
      Staphylococcus aureus in carriers from an intensive care unit.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a serious
      nosocomial problem, globally distributed. Decolonization with mupirocin can be
      used to control its dissemination. OBJECTIVE: To determine the incidence of
      mupirocin resistance among MRSA carriers from an intensive care unit. METHODS: We
      obtained 2723 nasal swabs during 3 years. Resistance to methicillin and mupirocin
      were verified (agar diffusion and the E test) and confirmed by polymerase chain
      reaction (PCR) (mecA for methicillin; ileS-2 and mupA for mupirocin). Plasmid
      curing procedure and pulsed-field gel electrophoresis (PFGE) were employed in
      isolates exhibiting high resistance to mupirocin (HR-Mup) and in other selected
      organisms. RESULTS: The overall incidence of HR-Mup among MRSA carriers during
      the studied period was 4.84% (8/165); however, the incidence decreased from
      13.04% (6/46) in the first year to 3.5% (2/57) in the second year and was 0% in
      the last year (P = .02). LR-Mup, in contrast, increased significantly (P = .01).
      CONCLUSION: Plasmid-curing procedure showed the plasmid location of genes
      responsible for HR-Mup. PFGE demonstrated that most MRSA, including the isolates
      with HR-Mup, were genetically related. The decline in HR-Mup may be attributable
      to the plasmid location of genes (ileS-2/mupA) and to the fact that all patients
      colonized with HR-Mup MRSA died or were discharged in a relatively short period
      of time.

PMID- 16443087
TI  - MRSA acquisition in an intensive care unit.
AB  - BACKGROUND: This paper describes a retrospective investigation of methicillin
      resistant Staphylococcus aureus (MRSA) acquisition in an 8-bed intensive care
      unit (ICU) over a 5-month period. METHODS: Clinical and microbiologic data were
      collected from the ICU, including MRSA detection dates, patient dependency
      scores, standardized environmental screening data, weekly bed occupancies, number
      of admissions, and nurse staffing levels. MRSA acquisition weeks were defined as
      weeks during which initial delivery of MRSA occurred before sampling and
      laboratory confirmation. Weekly workloads were plotted against staffing levels
      and modelled against MRSA acquisition weeks and hygiene failures. RESULTS: Of 174
      patients admitted into the ICU, 28 (16%) were found to have MRSA; 12 of these
      (7%) acquired MRSA on the ICU within 7 of the 23 weeks studied. Six of these 7
      weeks were associated with a deficit of trained nurses during the day and 5 with
      hygiene failures (data unavailable for 2). Pulsed-field gel electrophoresis
      (PFGE) profiles demonstrated relationships between staphylococci from staff
      hands, hand-touch sites, and patients' blood. CONCLUSION: MRSA acquisition in the
      ICU was temporally associated with reduced numbers of trained nurses and hygiene
      failures predominantly involving hand-touch sites. Epidemiologic analysis
      suggested that patient acquisitions were 7 times more likely to occur during
      periods of nurse understaffing.

PMID- 16443088
TI  - Mentor's hand hygiene practices influence student's hand hygiene rates.
AB  - BACKGROUND: There were 3 objectives for this prospective quasiexperimental study.
      The first was to determine the effect of mentor's hand hygiene practices on
      student's hand hygiene rates during clinical rotations. The second was to assess
      the difference in hand hygiene rates for students with and without prior medical
      experience. The third was to assess the student's opinion and beliefs regarding
      hand hygiene. METHODS: Sixty students enrolled in a certified nursing program
      were selected to participate in the study. Each study group was observed twice
      during the 30-day span. The first observational period was conducted on day 1 of
      clinical rotation. The second observational period was conducted on day 30 of
      clinical rotation. Students were observed for hand hygiene. Also assessed were
      medical experience, sex, gloving, age, and mentor's hand hygiene practices. After
      observational period 2, a brief questionnaire was given to students to determine
      their opinion and beliefs regarding hand hygiene. The questionnaire was divided
      into 5 sections: student's commitment to hand hygiene, their perception of hand
      hygiene inconvenience, the necessity of hand hygiene, the student's ability to
      perform hand hygiene, and their opinion on the frequency of medical staff's hand
      hygiene. RESULTS: The mentor's practice of hand hygiene was the strongest
      predictor of the student's rate of hand hygiene for both observational periods (P
      < .01). Furthermore, students without prior medical experience had a significant
      increase in hand hygiene rates when comparing observational period 1 to
      observational period 2 (P < .01). Glove usage was associated with increased hand
      hygiene rates by 50% during observational period 1 (P = .01) and 44% during
      observational period 2 (P < .01). Male students during observational period 1
      practiced hand hygiene 30% less often than female students (P < .01); however,
      during observational period 2, there was no significant difference between hand
      hygiene rates for males and females (P = .82). Questionnaires were completed by
      47 students, who reported a strong commitment to hand hygiene, belief in its
      necessity, and ability to perform hand hygiene (with scores in the high 90s on a
      10 to 100 rating scale). CONCLUSION: Mentor's use of hand hygiene and glove usage
      was associated with increased hand hygiene among students. Even though students
      reported strongly positive attitudes toward hand hygiene, students had a low
      overall rate of hand hygiene.

PMID- 16443089
TI  - Patient safety perceptions: a survey of Iowa physicians, pharmacists, and nurses.
AB  - BACKGROUND: Patient safety is of concern to consumers, health professionals,
      policymakers, insurers, and researchers. OBJECTIVE: Assess the perceptions of
      health care providers regarding the impact of parts of the health care system on
      patient safety, barriers to patient safety, and strategies to improve patient
      safety. METHODS: Statewide survey mailed in May 2001. Participants rated the
      impact of 10 parts of the health care system on patient safety, selected barriers
      to patient safety that they thought should be priorities, and selected the best
      strategies for improving patient safety. RESULTS: Of random samples of 1310
      physicians, 1310 pharmacists, and 2620 nurses licensed by the state of Iowa, 5075
      providers were eligible and 2388 responded (47%). Provider education, norms and
      values, patient and family characteristics, and continuity of care were rated as
      having a major impact on patient safety by at least 70% of each provider group. A
      general lack of consensus exists among providers about which barriers to patient
      safety should be priorities and which strategies would best improve the system.
      However, a majority of providers agreed that educating patients about their role
      in health care and sharing information between providers and across settings of
      care are important strategies for improving patient safety. CONCLUSION: In areas
      in which providers agree on the best strategies, broader, system-wide
      interventions that include physicians, pharmacists, and nurses in multiple
      settings may be implemented to improve patient safety. Health care organizations
      and providers must get patients more involved in their care by asking them to
      help define roles, design educational materials, and develop useful methods of
      sharing information across settings.

PMID- 16443090
TI  - Comparative efficacy of ethanol and isopropanol against feline calicivirus, a
      norovirus surrogate.
AB  - BACKGROUND: Improper disinfection of environmental surfaces contaminated by the
      feces or vomitus of infected patients is believed to be a major cause of the
      spread of noroviruses (NoV) in close institutional settings. Although several
      disinfectants are available, the search for safe and effective disinfectant
      continues. Because alcohol and alcohol-based products have been used as
      antiseptics and their efficacy against several enveloped viruses has been
      documented, we wanted to determine their efficacy against nonenveloped
      calicivirus. METHODS: Feline calicivirus (FCV) was used as a surrogate for NoVs,
      using the carrier test. We evaluated the virucidal efficacy of various
      concentrations of ethanol and isopropanol against FCV, dried on an inanimate,
      nonporous contact surface for contact times of 1, 3, and 10 minutes. The virus
      was eluted after alcohol treatment and titrated in feline kidney cells.
      Percentage virus inactivation was calculated by comparing these titers with those
      obtained with virus eluted from controls. RESULTS: Ethanol at 70% and 90% and
      isopropanol at 40% to 60% concentrations were found to be the most effective,
      killing 99% of FCV within a short contact time of 1 minute. CONCLUSION:
      Isopropanol was more efficacious than ethanol at 40% to 60% concentrations,
      suggesting that the use of an appropriate concentration of isopropanol or ethanol
      would help in controlling the transmission of NoVs from environmental contact
      surfaces.

PMID- 16443092
TI  - Survival on uncommon fomites of feline calicivirus, a surrogate of noroviruses.
AB  - BACKGROUND: Norovirus (NoV) transmission occurs mainly through food and fomites.
      Contaminated human fingers can transfer the virus to inanimate objects, which may
      then spread the virus to susceptible persons. However, no information is
      available on the survival of NoVs on fomites, which may be of importance in the
      transmission of NoVs in institutional settings such as hospitals and nursing
      homes. METHODS: In the absence of any in vitro cultivation system for NoVs,
      feline calicivirus (FCV) was used as a surrogate. Several fomites such as
      computer mouse, keyboard keys, telephone wire, telephone receiver, telephone
      buttons, and brass disks representing faucets and door handle surfaces were
      artificially contaminated with known amounts of FCV. Samples were taken at
      regular time intervals, and virus was titrated in feline kidney cells to
      determine its survival on these surfaces. RESULTS: Survivability of FCV varied
      with fomite type. The virus survived for up to 3 days on telephone buttons and
      receivers, for 1 or 2 days on computer mouse, and for 8 to 12 hours on keyboard
      keys and brass. The time for 90% virus reduction was <4 hours on computer keys,
      mouse, brass, and telephone wire; 4 to 8 hours on telephone receiver; and 12 to
      24 hours on telephone buttons. CONCLUSION: The results of this study confirm that
      FCV (and perhaps NoV) can survive on fomites such as computers, telephones, and
      faucets and may be transmitted to humans using these contaminated materials. This
      may necessitate regular cleaning or disinfection of these items, especially in
      hospitals and nursing homes and after known outbreaks of NoVs.

PMID- 16443091
TI  - Colonization and molecular epidemiology of coagulase-negative Staphylococcal
      bacteremia in cancer patients: a pilot study.
AB  - BACKGROUND: Controversy surrounds the source (skin vs mucosa) of coagulase
      negative staphylococci (CoNS) bacteremia in cancer patients. Determining the
      source of this infection has clinical and epidemiologic implications. OBJECTIVE:
      To determine the source(s) of CoNS bacteremia in cancer patients. METHODS:
      Between November 1998 and October 2000, cultures of nasal and rectal mucosa and
      skin at central venous catheter (CVC) sites were obtained in 62 patients (66
      episodes) with CoNS-positive blood culture(s). Bacteremia was classified as true,
      indeterminate, or unlikely on the basis of clinical and microbiologic findings.
      Molecular relatedness of strains isolated from the blood and from colonized sites
      of patients with true and those with unlikely bacteremia was examined using
      pulsed-field gel electrophoresis (PFGE). RESULTS: CoNS colonization was present
      in 55 episodes (83%). The nasal mucosa was the most frequently colonized site
      (86%), followed by rectal mucosa (40%) and skin at site of CVC insertion (38%) (P
      < .001). Colonization at > or =1 site was common. True and unlikely bacteremia
      accounted for 11 and 10 episodes, respectively, with the remaining 45 episodes
      considered undetermined or had negative surveillance cultures. Among patients
      with true bacteremia, 6 mucosal isolates and only 1 skin isolate were related by
      PFGE to the blood isolate recovered from the same patient. CONCLUSION: Mucosa is
      the most common site of CoNS colonization and is the likely source of CoNS
      bacteremia in cancer patients.

PMID- 16443093
TI  - Controlling the usage of intranasal mupirocin does impact the rate of
      Staphylococcus aureus deep sternal wound infections in cardiac surgery patients.
AB  - BACKGROUND: Staphylococcus aureus (S aureus) is the major cause of surgical site
      infections (SSI). At The Christ Hospital, Cincinnati, OH, S aureus accounted for
      over 80% of sternal wound infections in cardiac surgery patients. Approximately
      700 cardiac surgeries are performed each year, with an associated infection rate
      of 1.8% per 100 procedures performed. In an attempt to reduce S aureus sternal
      wound infections, the use of prophylactic intranasal mupirocin was examined.
      METHODS: Each patient undergoing cardiac surgery was nasally cultured before
      entering the operating room, and then intranasal mupirocin was applied and
      continued every 12 hours. Culture results were finalized within 48 hours.
      Mupirocin was discontinued when the culture returned negative and continued for 7
      days when the culture returned positive for S aureus. RESULTS: Cultures showed a
      S aureus carrier rate of 21%. These patients received mupirocin for 7 days. A
      decrease in S aureus-associated SSI rates was observed from a case rate of 1.68%
      to 0.37% per 100 procedures over a 17-month period. CONCLUSION: Identifying and
      treating S aureus carriers with a full course of mupirocin does impact the rate
      of S aureus surgical site infections.

PMID- 16443094
TI  - Prevention of infection spreading by cleaning and disinfecting: Different
      approaches and difficulties in communicating.

PMID- 16443096
TI  - Anatomy of the distal brachioradialis and its potential relationship to distal
      radius fracture.
AB  - PURPOSE: To describe the anatomy of the brachioradialis (BR), paying special
      attention to its insertion in relation to the surrounding structures in cadavers
      and evaluating and correlating this information with a distal radius fracture
      pattern in a clinical population. METHODS: Eighteen fresh-frozen cadaver arms
      were dissected to observe the gross anatomy of the BR. The dimensions of the
      insertion were measured using a caliper and a 3-dimensional digitizer. The
      radiographs of 34 patients with 35 distal radius fractures were reviewed and the
      fracture pattern was compared with the normalized location of the BR insertion
      based on the cadaver measurements. RESULTS: On average the BR tendon inserted
      onto the proximal base of the first dorsal compartment 17 mm from the radial
      styloid tip and extended 15 mm proximally; the insertion was 11 mm wide. The BR
      insertion was bordered consistently by both septa of the first dorsal
      compartment, forming a tunnel-like structure of thick fibrous tissue on the
      radial aspect of the distal radius. The whole length of the tendon attached
      firmly to the underlying antebrachial fascia, which limited excursion. In 18 of
      the fractures the fracture line deviated from transverse to proximal at the
      radial side, forming a radial beak. The proximal tip of the beak correlated with
      the expected location of the proximal end of the BR tendon insertion.
      CONCLUSIONS: The BR distal tendon insertion is a consistent, distinct insertion
      at the base of the first dorsal compartment, which correlates with the radial
      beak fracture pattern in approximately 50% of distal radius fractures. Cutting
      the BR tendon disconnects the distal fragment from the BR muscle and the forearm
      fascia, which may facilitate reduction of the distal radial fragments during open
      reduction of the distal radius fracture.

PMID- 16443097
TI  - Volar versus dorsal plating in the management of intra-articular distal radius
      fractures.
AB  - PURPOSE: To compare the complications and functional and radiographic outcomes of
      volar and dorsal plating of intra-articular distal radius fractures. METHODS:
      This retrospective review included 34 patients found by searching a database of
      350 patients treated for distal radius fractures. Inclusion criteria were (1) at
      least 1 year of follow-up data and (2) open reduction and internal fixation of a
      multifragmentary fragment intra-articular distal radius fracture with either a
      nonlocking volar or dorsal plate. Twenty patients were treated with a dorsal
      plate and 14 patients were treated with a volar nonlocking plate. Objective and
      subjective outcome parameters were compared between the 2 groups. Objective
      evaluations included wrist range of motion, grip strength, and preoperative and
      postoperative radiographic parameters (radial inclination, palmar tilt, ulnar
      variance, fracture pattern). Subjective evaluations were performed using the
      Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire score and the
      Gartland and Werley score. RESULTS: Volar plating resulted in a significantly
      better Gartland-Werley score compared with dorsal plating. There were no
      significant differences in the DASH score. Volar collapse was documented in 5 of
      the 20 patients in the dorsal plating group, which resulted in a mild loss of
      pronation compared with the volar plating group. No collapse occurred in the
      volar plating group. In addition the difference in the percentage of wrist range
      of motion compared with the contralateral wrist was not significant. Dorsal
      plating was associated with a ruptured extensor indicis tendon in 1 patient;
      secondary surgical procedures were required in 4 patients (tenolyses and radial
      styloidectomy). Volar plating was associated with median nerve neuropathy in 2
      patients and intersection syndrome in one. CONCLUSIONS: Although both groups of
      patients had similar DASH scores the functional outcome in terms of Gartland and
      Werley scores was better in the volar plating group. In addition there was a
      higher rate of volar collapse and late complications in the dorsal plating group
      compared with the volar plating group. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic, Level III.

PMID- 16443098
TI  - Isolated radial shaft fractures are more common than Galeazzi fractures.
AB  - PURPOSE: In contrast to isolated diaphyseal fractures of the ulna (so-called
      night-stick fractures), isolated fractures of the radial diaphysis generally are
      expected to have associated injury of the distal radioulnar joint (DRUJ), the so
      called Galeazzi fracture. This study retrospectively reviewed isolated fractures
      of the radial diaphysis in a large cohort of patients to determine how often such
      fractures occur without DRUJ injury METHODS: Thirty-six patients with fracture of
      the radius without fracture of the ulna were followed up for at least 6 months
      after injury. Injury of the DRUJ was defined as more than 5 mm of ulnar-positive
      variance on radiographs taken before any manipulative or surgical reduction. All
      of the fractures were treated with plate and screw fixation (8 with autogenous
      bone grafting) and all healed. Patients with DRUJ injury had either temporary
      pinning or immobilization of the DRUJ or surgical fixation of a large ulnar
      styloid fracture. Patients without DRUJ injury were mobilized within 2 weeks.
      RESULTS: Nine patients had dislocation of the DRUJ, 4 with large ulnar styloid
      fractures. Among the remaining 27 patients 1 had displacement of the proximal
      radioulnar joint noted after surgery, leading to a secondary procedure for radial
      head resection. The functional results were satisfactory or excellent in all but
      2 patients with functional limitations related to central nervous system injury.
      No patient had DRUJ dysfunction at the final follow-up evaluation. CONCLUSIONS:
      Isolated fractures of the radial diaphysis are more common than true Galeazzi
      fractures. Surgeons should take great care not to overlook injury to the distal
      or proximal radioulnar joint in association with isolated diaphyseal fractures of
      the radius; however, fractures without identifiable radioulnar disruption can be
      treated without specific treatment of the DRUJ and with immediate mobilization.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

PMID- 16443099
TI  - Radiographic parameters of increased carpal tunnel pressure with progressive
      wrist distraction: a cadaveric study.
AB  - PURPOSE: Increased carpal canal pressure associated with external fixation has
      been noted as a potential source of complications but no correlated clinical
      observation has been identified. We hypothesized that there would be a
      significant change in midcarpal distance and modified carpal height index with
      increasing distraction across the wrist joint and that these changes would
      correlate with pressure increases. METHODS: Thirteen cadaveric upper extremities
      were mounted vertically using 2 half pins in the midradius. Using a previously
      reported technique, we introduced a balloon-tipped catheter attached to a
      transducer into the carpal canal for pressure measurement. As weights were hung
      from the middle finger to create distraction across the carpus, pressure
      measurements and radiographs of the wrist were taken simultaneously. This
      sequence was performed for 4.50 kg of distraction in 0.45-kg increments and at
      6.80 and 9.07 kg of distraction with the wrist in neutral position. Changes in
      midcarpal distance and modified carpal height index were calculated and
      comparisons were made with the Student t test. A 2-tailed Pearson correlation was
      used to determine whether there was a correlation between carpal canal pressure
      and radiographic indicators. Significance was set at p<or=.05. RESULTS: A
      statistically significant increase in carpal canal pressure above baseline
      occurred at a load of 1.81 kg. The increase in the midcarpal space and modified
      carpal height index became significant at a load of 1.81 kg. The change in
      pressure and the changes in radiographic indicators correlated significantly
      (p<.01). CONCLUSIONS: This preliminary cadaveric study found a small but
      significant increase in modified carpal height index with wrist distraction that
      correlated with increased carpal canal pressure. Further biomechanical and
      clinical studies are needed to determine recommended parameters for change in
      modified carpal height index with wrist distraction clinically.

PMID- 16443100
TI  - Innervation of the wrist joint and surgical perspectives of denervation.
AB  - PURPOSE: Because our experience with the techniques used in denervation surgery
      of the wrist joint often has proven insufficient in treating chronic pain we
      conducted an anatomic study to clarify the exact contributions of the nerves
      supplying the wrist joint. Our goal was to reveal all periosteal and capsular
      nerve connections and if necessary adjust our technique used in denervation
      surgery. METHODS: Innervation of the wrist joint was investigated by
      microdissection and histologic examination of 18 human wrists. An
      acetylcholinesterase method was used to identify the nerves, both in whole-mount
      preparations and in sections. RESULTS: We found that the main innervation to the
      wrist capsule and periosteal nerve network came from the anterior interosseous
      nerve, lateral antebrachial cutaneous nerve, and posterior interosseous nerve.
      The palmar cutaneous branch of the median nerve, the deep branch of the ulnar
      nerve, the superficial branch of the radial nerve, and the dorsal branch of the
      ulnar nerve also were found to have connections with the capsule. The periosteal
      nerve branches did not appear to play a major role in the innervation of the
      capsule and ligaments; here the specific articular nerve branches proved more
      important. The posterior and medial antebrachial cutaneous nerves did not connect
      to the wrist capsule or periosteum but rather terminated in the extensor and
      flexor retinaculum. CONCLUSIONS: Based on our findings we propose to denervate
      the wrist by making 2 incisions. With one palmar and one dorsal incision it
      should be possible to disconnect the periosteum from the capsule and interrupt
      the majority of the capsular nerve branches.

PMID- 16443101
TI  - The effects of experimental neurolysis on ectopic firing in a rat chronic
      constriction nerve injury model.
AB  - PURPOSE: We studied the effects of experimental neurolysis on ectopic firing in a
      rat chronic constriction nerve injury (CCI) model. METHODS: Sixteen Wistar rats
      were used as CCI models; 8 in a neurolysis group and 8 in a sham operation group.
      Eight additional Wistar rats were used in a normal control group. The CCI model
      was created by loosely ligating the sciatic nerve with 4-0 chromic gut sutures.
      Seven days after surgery the same portion of the sciatic nerve, now embedded in
      scar tissue, was exposed. For the neurolysis group all sutures and scar tissue
      around the nerve were removed, and for the sham operation group only exposure of
      the sciatic nerve embedded in scar tissue was performed. Fourteen days after the
      first surgery the spinal cords of all animals in the 3 groups were transeated at
      the most rostral level of the spinal cord and ectopic firing was recorded
      antidromically from the sural nerve. The spontaneous ectopic firing frequency and
      the firing pattern at rest and the ectopic firing frequency under a hypoxic
      condition were analyzed. RESULTS: The ectopic firing frequency in the neurolysis
      group was significantly lower than that of the sham operation group but higher
      than that of the normal control group. Also the appearance rate of an on-off
      pattern was 0% in the neurolysis and normal control groups and 38% in the sham
      operation group. Finally the accumulated number of ectopic firings under a
      hypoxic condition was significantly smaller in the neurolysis and normal control
      groups than that of the sham operation group. CONCLUSIONS: Experimental
      neurolysis significantly improved the abnormal ectopic firing frequency and on
      off firing pattern in the injured nerve of the CCI model. These findings may
      explain the efficacy of neurolysis on sensory symptoms such as numbness or
      spontaneous pain in chronic compression neuropathy.

PMID- 16443102
TI  - Intraneural ganglion of the suprascapular nerve: case report.
AB  - We present a case of multicystic ganglion of the suprascapular nerve in an 18
      year-old man. Pain and shoulder weakness were present and examination showed
      weakness and atrophy of the supraspinatus and infraspinatus muscles.
      Electromyography showed severe denervation of the infraspinatus and supraspinatus
      muscles. At surgery a multicystic lesion of the suprascapular nerve extending
      approximately 5.7 cm from its origin was resected and reconstructed by sural
      nerve grafting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level V.

PMID- 16443103
TI  - Coronoid fracture patterns.
AB  - PURPOSE: It has been suggested that specific types of coronoid fractures are
      associated strongly with specific patterns of traumatic elbow instability. This
      hypothesis was tested in a review of a large consecutive series of patients with
      a fracture of the coronoid as part of a fracture-dislocation of the elbow.
      METHODS: One surgeon repaired 67 coronoid fractures as part of a fracture
      dislocation of the elbow over a 7-year period. Each coronoid fracture was
      characterized on the basis of surgical exposure. Pearson chi-square analysis was
      used to evaluate the association of the coronoid fracture type with 1 of 4 common
      patterns of elbow fracture-dislocation. RESULTS: The coronoid fracture was
      associated with an anterior (6 patients) or posterior (18 patients) olecranon
      fracture-dislocation in 24 patients, an elbow dislocation and radial head
      fracture in 32 patients, and a varus posteromedial rotational instability pattern
      injury in 11 patients. Among the 24 patients with olecranon fracture-dislocations
      22 had large coronoid fractures and 2 had small (<50%) coronoid fractures. All 32
      patients with terrible-triad injuries had small (<50%) coronoid fractures with 1
      of these being a fracture of the anteromedial facet of the coronoid. Among
      patients with varus posteromedial rotational pattern injuries 9 had small
      fractures of the anteromedial facet and 2 had larger fractures. The association
      of coronoid fracture type with injury pattern was strongly statistically
      significant for both classification systems. CONCLUSIONS: The following strong
      associations were confirmed by this study: large fractures of the coronoid
      process with anterior and posterior olecranon fracture-dislocations, small
      transverse fractures with terrible-triad injuries, and anteromedial facet
      fractures with varus posteromedial rotational instability pattern injuries. An
      awareness of these associations and their exceptions may help guide the optimal
      management of these injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level
      IV.

PMID- 16443104
TI  - Reference points for radial head prosthesis size.
AB  - PURPOSE: Metallic radial head implants are useful when the radial head cannot be
      repaired reliably and when either the elbow or the forearm is unstable. Problems
      arise when the radial head prosthesis is too thick, causing erosions of the
      capitellum and incongruity of the ulnohumeral joint. We used quantitative 3
      dimensional computed tomography analysis to investigate the relative height of
      the radial head relative to the lateral edge and central ridge of the coronoid
      process as reference points for optimal insertion of a radial head prosthesis.
      METHODS: Seventeen computed tomography scans of the elbow were analyzed. The
      anatomic coronal plane of the forearm was determined using 3-dimensional images
      and a 2-dimensional image bisecting the articular surface of the radial head was
      created in this plane. The distance between the plane of the articular surface of
      the radial head and parallel planes at the most proximal aspect of the coronoid
      (the central ridge) and the lateral edge of the coronoid articular surface were
      measured. Negative values indicate the radial head is proximal to the coronoid.
      RESULTS: The average distance between the planes defined by the radial head
      articular surface and the coronoid central ridge was -0.8 mm. The average
      distance between the planes defined by the radial head articular surface and the
      lateral edge of the coronoid articular surface was -0.9 mm. CONCLUSIONS: Because
      the radial head was on average only 0.9 mm more proximal than the lateral edge of
      the coronoid process and because the key is to not overstuff the joint a useful
      general guideline would be to place the plane of the articular surface of the
      radial head even with or just slightly more proximal than the lateral edge of the
      coronoid articular surface. Considering the substantial variability of the normal
      height of the articular surface of the radial head with respect to that of the
      coronoid, preoperative radiographs of the opposite elbow may be useful to avoid
      overstuffing the elbow.

PMID- 16443105
TI  - Loading of the index metacarpal after trapezial and partial versus complete
      trapezoid resection.
AB  - PURPOSE: To examine the effects of partial or complete trapezoidectomy in
      conjunction with trapezium resection on proximal migration of the index
      metacarpal during axial loading. METHODS: Five specimens from below the elbow
      were obtained from fresh-frozen cadavers. A customized vise was used to position
      the wrist in 20 degrees extension and 5 degrees ulnar deviation, simulating a
      power grip. The index metacarpal was instrumented to allow axial loading at 125 N
      and 250 N. Specimens were tested under 4 experimental conditions: (1) in the
      intact state, (2) after trapezial resection, (3) after partial trapezoid
      resection, and (4) after complete trapezoid resection. Specimens were tested 5
      times under each experimental condition, displacement was measured with a linear
      variable differential transformer, and stiffness was calculated. RESULTS: There
      was no difference in stiffness between the different treatments at either 125 N
      or 250 N. Displacement was not significantly different between treatments for
      loads of 125 N. For loads of 250 N the displacement was approximately 1 mm
      greater with complete trapezoid resection than with any of the other treatment
      conditions. Displacement did not differ significantly between the other 3
      treatments. CONCLUSIONS: The addition of a partial trapezoid resection performed
      at the time of trapezial resection does not affect proximal migration of the
      second metacarpal. When a complete trapezoidectomy is performed at the time of
      trapezial excision, however, the loading characteristics of the index metacarpal
      do change statistically significantly, although the magnitude of that change is
      only approximately 1 mm. Further testing will be necessary to elucidate the
      biomechanical effects of a partial trapezoid resection in conjunction with a
      trapezial resection on the second metacarpal in other planes.

PMID- 16443106
TI  - Time course of magnetic resonance images in an adolescent patient with Kienbock's
      disease treated by temporary scaphotrapezoidal joint fixation: a case report.
AB  - Kienbock's disease in a 15-year-old girl was treated successfully by temporary
      scaphotrapezoidal joint fixation using longitudinal K-wires. Repeated magnetic
      resonance imaging begun 3 months after surgery showed progressive increases in
      signal intensity on T1-weighted sequences of the lunate and was almost normal 6
      months after surgery. The K-wires used for the temporary joint fixation were
      removed 6 months after surgery. The signal intensity of the lunate on magnetic
      resonance images remained normal 2 years after surgery. At that time plain x-ray
      showed no sign of lunate sclerosis and there was no cystic shadow or sign of
      advanced collapse. At 2 years after surgery the patient does not complain of
      wrist pain, can lead a normal daily life, and plays sports without difficulty.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

PMID- 16443108
TI  - Measurement of rotation of the first metacarpal during opposition using computed
      tomography.
AB  - PURPOSE: Opposition is an important movement of the hand and rotation of the
      first metacarpal is the essential component. There is no agreement on the exact
      magnitude of rotation of the first metacarpal during opposition. This study used
      computed tomography to describe rotation measurement of the first metacarpal in
      the hands of a group of healthy individuals. METHODS: The rotation of the first
      metacarpal was measured with reference to the fixed unit of the hand. Computed
      tomographic images were taken of the hands of 10 healthy individuals with the
      thumb in retroposition, resting position, and opposition to the index, middle,
      ring, and small fingers. On each image a tangential line was drawn along the
      dorsal margin of the second and third metacarpals. A second line was drawn
      through the head of the first metacarpal at the level of the sesamoids. The angle
      between the 2 lines was measured as the angle of rotation of the first metacarpal
      in different thumb positions. RESULTS: The mean angle of rotation of the first
      metacarpal in retroposition was 54 degrees+/-10 degrees with reference to the
      fixed unit of the hand. In the resting position the angle of rotation of the
      first metacarpal changed to 74 degrees+/-10 degrees. In the position of
      opposition to the index, middle, ring, and small fingers the angle of rotation of
      the first metacarpal increased to 100 degrees+/-7 degrees , 103 degrees+/-6
      degrees, 105 degrees+/-6 degrees, and 110 degrees+/-7 degrees, respectively.
      CONCLUSIONS: The first metacarpal rotates 56 degrees when it moves from
      retroposition to the position of opposition to the small finger.

PMID- 16443107
TI  - Results of surgical treatment of acute and chronic grade III [corrected] tears of
      the radial collateral ligament of the thumb metacarpophalangeal joint.
AB  - PURPOSE: Radial collateral ligament (RCL) injuries of the thumb
      metacarpophalangeal (MCP) joint are much less common than ulnar collateral
      ligament injuries. Cast or splint immobilization is recommended for treating
      grade I and grade II tears; however, there is no consensus for treating grade III
      (complete) tears of the RCL. The purpose of this study was to assess the results
      of repair of acute grade III tears of the RCL and evaluate the efficacy of late
      reconstruction for chronic instability. METHODS: From 1986 to 2001 there were 26
      patients (16 in the repair group, 10 in the reconstruction group) who were
      reviewed retrospectively and examined clinically after either repair or
      reconstruction of the RCL of the thumb. The repair group had surgery at a mean of
      2.5 weeks after injury and was evaluated at a mean follow-up time of 4.6 years.
      The reconstruction group had surgery at a mean of 6.8 months after injury and was
      evaluated at a mean follow-up time of 5.0 years. RESULTS: At an average follow-up
      of 59 months, there were no statistically significant differences in MCP or
      interphalangeal joint motion, grip or pinch strength, or MCP joint stability
      between the 2 groups. Based on a newly developed grading system there were 12
      excellent and 3 good results in the repair group and 8 excellent and 2 good
      results in the reconstruction group. Overall satisfaction was excellent for both
      groups. CONCLUSIONS: We recommend the repair of acute grade III RCL injuries and
      reconstruction of chronic grade III RCL tears of the thumb MCP joint to prevent
      the development of a painful unstable thumb and possibly to prevent the
      development of MCP joint arthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic,
      Level IV.

PMID- 16443109
TI  - Immunohistochemical detection of relaxin binding to the volar oblique ligament.
AB  - PURPOSE: Excess laxity in the volar oblique ligament may predispose the thumb to
      trapeziometacarpal joint osteoarthritis. A greater prevalence of
      trapeziometacarpal joint osteoarthritis in women suggests a hormonal cause and
      relaxin is a hormone that may have some involvement. This conclusion emerges from
      relaxin's diverse tissue tropism, stimulation of collagenase production in
      cultured fibroblasts, and reports of increased joint laxity during pregnancy. We
      used immunohistochemistry to assess the potential of the volar oblique ligament
      to bind relaxin. METHODS: Eight volar oblique ligaments were obtained
      intraoperatively from perimenopausal women having basal joint arthroplasty with
      ligament reconstruction using the flexor carpi radialis tendon. Tissue specimens
      were snap-frozen in liquid nitrogen and stored at -80 degrees C until processing.
      Specimens then were cryosectioned, treated with a chelating rinse, incubated
      overnight with recombinant human relaxin, fixed, blocked, and exposed to
      antirelaxin antibody. Treatment with a universal aminoethylcarbizole staining kit
      was used to visualize areas of ligament-ligand binding. Both tissue and
      procedural controls served to establish binding specificity. RESULTS: Abundant
      staining was observed with the positive control (cervix) and all 8 volar oblique
      ligaments. Little or no staining was present in fibrocartilage (negative control)
      or procedural controls. CONCLUSIONS: Relaxin binds to the volar oblique ligament
      with specificity, implying a receptor-mediated process. Limitations of the
      procedure could not confirm binding saturability, necessitating additional study.

PMID- 16443110
TI  - Use of a headless compressive screw for distal interphalangeal joint arthrodesis
      in digits: clinical outcome and review of complications.
AB  - PURPOSE: Arthrodesis of the distal interphalangeal joint (DIPJ) or thumb
      interphalangeal joints can be necessary to treat pain, deformity, or instability
      associated with arthritis. Compression and rigid fixation are thought to
      influence fusion rates and time to union favorably. The purpose of the study was
      to review the clinical outcome and complications associated with the use of a
      fully threaded headless compression screw for DIPJ arthrodesis. METHODS: Twenty
      seven distal interphalangeal or thumb interphalangeal fusions were performed with
      an axial Mini-Acutrak screw in 22 patients. Charts, surgical reports, and
      preoperative and postoperative x-rays were reviewed to determine the incidence,
      time to union, and complications. The minimal follow-up period was 3 months.
      RESULTS: Twenty-three of the 27 arthrodeses achieved bony union. Complications
      included symptomatic nonunion (n=1, treated with secondary fusion), asymptomatic
      nonunion (n=2, left untreated), infection (n=4; 2 patients required implant
      removal that resulted in nonunion but declined revision) and nail bed injury
      (n=3). CONCLUSIONS: The Mini-Acutrak screw technique achieves healing rates that
      are comparable with but not superior to other techniques. Its main advantages are
      ease of execution, fully buried hardware, and early mobilization; however, the
      procedure is associated with complications and meticulous technique is required
      to avoid them. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

PMID- 16443111
TI  - Osseointegration and mechanical stability of pyrocarbon and titanium hand
      implants in a load-bearing in vivo model for small joint arthroplasty.
AB  - PURPOSE: To test the mechanical stability and histologic osseointegration under
      load-bearing conditions of 2 different materials, pyrocarbon (Py) and titanium
      (Ti), in a rabbit model. METHODS: Proximal interphalangeal implants (9 Ti, 8 Py)
      were placed into rabbit knees and the animals were killed after 3 months.
      Subsidence was assessed by monthly x-rays. Mechanical stability was measured with
      a nondestructive pullout test. Implant osseointegration was evaluated by an
      analysis of the relative implant-calcified bone contact surface on
      microradiographs and by a histomorphometric analysis of the percentage of bone
      and connective tissue contact with the implant surface. Histologic examination
      included assessment of bone apposition on the basis of fluorochromes. RESULTS:
      Subsidence was found in all 8 Py implants but in none of the Ti group. All 9 Ti
      implants were mechanically stable; all 8 Py implants were loose. A significantly
      higher implant-bone contact was found for the Ti group compared with the Py
      group. Bone apposition increased with time and was highest for the Ti implants 6
      weeks after implantation. CONCLUSIONS: In the rabbit model osseointegration of
      implants was highly dependent on the material. A reliable osseointegration was
      found for Ti implants. For Py implants no osseointegration or implant stability
      was achieved. For use of small joints of the hand we therefore recommend Ti-based
      implants.

PMID- 16443112
TI  - Treatment of enchondroma of the hand with injectable calcium phosphate bone
      cement.
AB  - PURPOSE: To report the results of treatment of enchondroma of the hand managed by
      curettage and calcium phosphate bone cement (CPC) grafting. METHODS: Ten patients
      with digital enchondroma were reviewed. There were 6 proximal phalanges, 2 middle
      phalanges, and 2 metacarpal bones. The average patient age at surgery was 31
      years. The average follow-up period was 41 months. We reviewed the final function
      and radiographic appearance of the surgically treated digits. We defined the term
      bony incorporation of CPC as a seamless change of radiographic appearance and no
      gap between cancellous bone and CPC. RESULTS: At final evaluation the bony
      incorporation was uneventful in all patients. Radiographs showed apparent partial
      absorption of CPC in only 2 patients. All digits had full range of motion after
      surgery. One digit fixed with multiple pins to treat a pathologic fracture
      simultaneously resulted in malunion and needed additional surgeries to correct
      digital overlap. No other complications were encountered. CONCLUSIONS: Patients
      with enchondroma of the hand are good candidates for treatment with CPC. In the
      case of pathologic fracture before surgery, however, surgery may be delayed until
      fracture healing because early corrective osteotomy with CPC might be difficult
      in a patient with malunion TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level
      IV.

PMID- 16443113
TI  - Subcutaneous granuloma annulare in a child's palm: a case report.
AB  - We present a rare case of subcutaneous lesions arising in the palm of a 4-year
      old girl. Histologic examination of the biopsy specimens showed granulomatous
      inflammation with focal necrobiosis, which was consistent with subcutaneous
      granuloma annulare. Subcutaneous granuloma annulare is a self-limited disease and
      treatment is not required, although recurrence and/or multiple lesions are
      frequent.

PMID- 16443114
TI  - Influence of core suture purchase length on strength of four-strand tendon
      repairs.
AB  - PURPOSE: Recently the length of core suture purchase has been identified as a
      variable affecting the strength of tendon repairs. The influence of the length of
      the core suture purchase on the strength of multistrand locking and grasping
      suture repairs, however, has not been studied extensively in transversely
      lacerated tendons. We assessed the effects of the length of the core suture
      purchase on the strength of three 4-strand grasping or locking repair techniques.
      METHODS: Seventy-four fresh adult pig flexor tendons were cut transversely and
      repaired with 1 of 3 methods: double-modified Kessler, locking cruciate, and
      modified Savage. Each method was assessed using 2 different lengths of core
      suture purchase (1.0 and 0.4 cm). The tendons were subjected to a linear
      noncyclic load-to-failure test in a tensile testing machine. We recorded the
      forces required for gap formation, ultimate strength, stiffness of the tendon,
      and the mode of repair failure. RESULTS: The resistance to gap formation, the
      ultimate strength of all 3 repairs, and the stiffness of the tendons with the
      double-modified Kessler and modified Savage repairs decreased significantly as
      the length of core sutures decreased from 1.0 to 0.4 cm. Locking and grasping
      repairs had a similar decrease in strength when the purchase was decreased from
      1.0 to 0.4 cm. All tendons with modified Savage repairs with 1.0-cm purchase
      failed by suture breakage and tendons with 0.4-cm purchase failed predominantly
      by pullout. CONCLUSIONS: The length of core suture purchase significantly affects
      the strength of these 4-strand tendon repairs. The forces required for gap
      formation and the ultimate failure of repairs with 0.4-cm purchase were 20% to
      45% lower than those of the repairs with 1.0-cm purchase. Locking repairs did not
      show a greater capacity to offset the decrease in strength than grasping repairs
      when the length of core suture purchase was decreased from 1.0 to 0.4 cm. Our
      study indicates that the length of suture purchase directly influences the
      strength of both locking and grasping core tendon repair methods.

PMID- 16443115
TI  - Effect of finger ulnar deviation on gliding resistance of the flexor digitorum
      profundus tendon within the A1 and A2 pulley complex.
AB  - PURPOSE: To evaluate the effect of ulnar deviation of the finger on gliding
      resistance of the flexor digitorum profundus tendon within the A1 and A2 pulley
      complex. METHODS: Thirty-two human cadaveric fingers (index through small
      fingers) were used. The gliding resistance was measured at 5 different angles of
      ulnar deviation (0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees).
      RESULTS: There was a significant increase in gliding resistance with increased
      ulnar deviation. The gliding resistances at 0 degrees, 15 degrees, 30 degrees, 45
      degrees, and 60 degrees of ulnar deviation were 0.40+/-0.13 N, 0.44+/-0.13 N,
      0.55+/-0.17 N, 0.74+/-0.21 N, and 1.02+/-0.30 N, respectively. The gliding
      resistance at 60 degrees was significantly greater than at all other angles; 45
      degrees ulnar deviation had significantly higher gliding resistance than 0
      degrees, 15 degrees, and 30 degrees; and 30 degrees ulnar deviation had
      significantly higher gliding resistance than 0 degrees. CONCLUSIONS: A greater
      angle of ulnar deviation causes higher gliding resistance during motion of the
      flexor digitorum profundus tendon within the A1 and A2 pulley complex. The
      gliding resistance increases significantly at angles greater than 30 degrees of
      ulnar deviation. The increased tendon loading needed to overcome increased
      gliding resistance caused by ulnar deviation could result in a vicious cycle of
      progressive ulnar deviation. Although mild degrees of ulnar deviation may be well
      tolerated mechanically a reasonable therapeutic guideline might be to prevent
      deviation from exceeding 30 degrees.

PMID- 16443116
TI  - Corrective osteotomies of the radius and ulna for supination contracture of the
      pediatric and adolescent forearm secondary to neurologic injury.
AB  - PURPOSE: To present the authors' experience with internal fixation of the radius
      and ulna as a surgical option for correction of supination contracture of the
      forearm. METHODS: Twelve patients (13 limbs) had an osteotomy of the radius and
      ulna for a supination deformity secondary to a residual brachial plexus or spinal
      cord injury. Surgery consisted of proximal ulna and distal radius osteotomies
      combined with plate fixation. RESULTS: The average age of the patients at the
      time of surgery was 11 years. Five limbs had fixed supination deformities and 8
      limbs lacked pronation beyond neutral. The average preoperative supination
      deformity (either fixed or measured at midarc) was 76 degrees. The average
      intraoperative correction was 86 degrees. The average follow-up period was 16
      months. The average midrange resting position maintained at final follow-up
      evaluation was 2 degrees of pronation. All limbs ultimately obtained radiographic
      and clinical union of the osteotomy sites. Complications included 6 plate
      fractures; however, only 1 patient required revision internal fixation.
      CONCLUSIONS: The combination of a proximal ulna and distal radius osteotomy with
      internal fixation can provide excellent correction, but the implant must be
      strong enough to hold the osteotomies rigidly in the corrected position during
      the time needed for union. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level
      IV.

PMID- 16443117
TI  - Three-ligament tenodesis for the treatment of scapholunate dissociation:
      indications and surgical technique.
AB  - Different surgical techniques have been proposed to treat traumatic scapholunate
      instability. Deciding which treatment is best for each individual case is not
      easy. In this article we report an algorithm of treatment based on a number of
      prognostic factors that may help in this matter. We also report on the promising
      results obtained using a new technique, the 3-ligament tenodesis, for the
      treatment of nonrepairable complete scapholunate ligament rupture, causing a
      reducible carpal malalignment without secondary osteoarthritis. This technique
      incorporates features from 3 previously described techniques.

PMID- 16443118
TI  - Trigger digits: principles, management, and complications.
AB  - Stenosing tenosynovitis, or trigger finger, is an entity seen commonly by hand
      surgeons. This problem generally is caused by a size mismatch between the flexor
      tendon and the first annular (A-1) pulley. Conservative management includes
      splinting, corticosteroid injection, and other adjuvant modalities. Surgical
      treatment consists of release of the A-1 pulley by open or percutaneous
      techniques. Complications are rare but include bowstringing, digital nerve
      injury, and continued triggering. Some patients require more extensive procedures
      to reduce the size of the flexor tendon. Comorbid conditions affect how trigger
      finger is treated. Patients with rheumatoid arthritis require tenosynovectomy
      instead of A-1 pulley release. In children trigger thumb resolves reliably with A
      1 pulley release but other digits may require more extensive surgery. In diabetic
      patients trigger finger often is less responsive to conservative measures. An
      understanding of the pathomechanics, risk factors, and varied treatments for
      trigger finger is essential for appropriate care.

PMID- 16443119
TI  - Gerdy's tubercle as a source of cancellous bone graft for surgery of the upper
      extremity: description of technique.
AB  - Cancellous bone grafts can be harvested from Gerdy's tubercle on the proximal
      metaphysis of the tibia for surgical procedures on the upper extremity. This
      donor site, however, is used rarely by hand surgeons, possibly because of a lack
      of awareness.

PMID- 16443120
TI  - Acute onset of nontraumatic upper-extremity atrophy.

PMID- 16443122
TI  - Nonmicrosurgical replantation using a subcutaneous pocket for salvage of the
      amputated fingertip.

PMID- 16443124
TI  - Mini-open blind procedure versus limited open technique for carpal tunnel
      release.

PMID- 16443127
TI  - Mechanisms of brain injury after global cerebral ischemia.
AB  - Cerebral ischemia results in a rapid depletion of energy stores that triggers a
      complex cascade of cellular events such as cellular depolarization and Ca2+
      influx, resulting in excitotoxic cell death. The critical determinant of severity
      of brain injury is the duration and severity of the ischemic insult and early
      restoration of CBF. Induced therapeutic hypothermia following CA is the only
      strategy that has demonstrated improvement in outcomes in prospective, randomized
      clinical trials. Although pharmacologic neuro-protection has been disappointing
      thus far in a variety of experimental animal models, further research efforts are
      directed at using some agents that demonstrate marginal or moderate efficacy in
      combination with hypothermia. Although the signal transduction pathways and
      intracellular molecular events during cerebral ischemia and reperfusion are
      complex, potential therapeutic neuroprotective strategies hold promise for the
      future.

PMID- 16443128
TI  - Prehospital and emergency department care to preserve neurologic function during
      and following cardiopulmonary resuscitation.
AB  - Considerable progress has been made in providing high-quality prehospital and
      emergency cardiac care for OHCA victims. The use of early CPR, early
      defibrillation, early ACLS, and state-of-the-art postresuscitation care offers
      the best promise for improved community survival and neurologic outcome
      statistics in the future. The NIH-sponsored Resuscitation Outcomes Consortium
      represents the largest governmentally sponsored effort of its kind that that will
      test the value of promising pharmacologic and device interventions on improving
      survival and neurologic outcome in OHCA patients.

PMID- 16443129
TI  - Intensive care after resuscitation from cardiac arrest: a focus on heart and
      brain injury.
AB  - Less than 3% of all patients who have out-of-hospital cardiac arrests have return
      of spontaneous circulation (ROSC), survive the hospitalization, and have a
      reasonable functional recovery. The fact that many patients who have ROSC
      ultimately die or fail to have favorable neurologic recovery suggests that
      processes that occur after hospitalization, especially in the ICU, have an impact
      on survival and neurologic recovery. This article addresses the acute care, with
      emphasis on the cardiac and neurologic aspects,that patients who have post
      cardiac arrest are provided in the cardiac ICU.

PMID- 16443130
TI  - Therapeutic hypothermia after cardiac arrest.
AB  - The use of IH for 24 hours in patients who remain comatose following
      resuscitation from out-of-hospital cardiac arrest improves outcomes. How-ever,
      the induction of hypothermia has several physiologic effects that need to be
      considered. A protocol for the rapid induction of hypothermia is described. At
      present, the rapid infusion of a large volume (40 mL/kg) of ice-cold crystalloid
      (ie, lactated Ringer's solution) would appear to be an inexpensive, safe strategy
      for the induction of hypothermia after cardiac arrest. Hypothermia (33 degrees C)
      should be maintained for 24 hours, followed by rewarming over 12 hours.
      Particular attention must be paid to potassium and glucose levels during
      hypothermia.

PMID- 16443131
TI  - Cerebral resuscitation: state of the art, experimental approaches and clinical
      perspectives.
AB  - Neuronal injury following global cerebral ischemia continues to bea central
      problem of patients in the postresuscitation phase following cardiocirculatory
      arrest. In addition to measures focusing on rapid restoration of spontaneous
      circulation, the most effective treatment after cardiac arrest, as shown by large
      randomized trials,is the use of therapeutic mild hypothermia. Current guidelines
      of the International Liaison Committee on Resuscitation (ILCOR)are recommending
      the use of therapeutic mild hypothermia for all unconscious patients after
      cardiac arrest. At present there is no specific neuroprotective treatment
      available. Promising animal experimental data concerning the use of thrombolytic
      agents during cardiopulmonary resuscitation have led to a large European
      multicenter trial (TROICA trial) that will provide its data in 2006.

PMID- 16443132
TI  - Clinical neurophysiologic monitoring and brain injury from cardiac arrest.
AB  - Electrophysiologic testing continues to play an important role in injury
      stratification and prognostication in patients who are comatose after cardiac
      arrest. As discussed previously, however, the adage about treating whole
      patients, not just the numbers, is relevant in this situation. EEG and SSEP can
      offer high specificity for discerning poor prognosis as long as they are applied
      to appropriate patient populations. As discussed previously, EEG and SSEP
      patterns change during the first hours to days after cardiac arrest and negative
      prognostic information should not be based solely on studies performed during the
      first 24 hours. Both electrophysiologic techniques also are susceptible to
      artifacts that may worsen the electrical patterns artificially and suggest a
      falsely poor prognosis. EEG is suppressed by anesthetic agents and hypothermia,
      both of which may produce ECS and burst suppression. Patients who experience
      respiratory arrest from a toxic ingestion of narcotics or barbiturates, in
      particular, may present with high-grade EEG patterns initially. Many patients
      also receive anesthetic medications at the time of tracheal intubation, which may
      linger beyond their normal half-life in patients who have hepatic or renal
      insufficiency or concurrent use of interacting medications. SSEP is much less
      susceptible to sedative anesthetic agents, but hypothermia is demonstrated to
      prolong evoked potential latencies. As therapeutic hypothermia becomes more
      common after cardiac arrest, the effect of temperature on electrophysiologic
      testing needs to be taken into account. The publications discussed previously
      also emphasize the need to adjust the prognostic value of electro-physiologic
      tests to the pretest probability of meaningful neurologic recovery in individual
      patients. Clearly, grade I EEG patterns and normal N20 potentials indicate a much
      better prognosis in patients who have a short du-ration of cardiac arrest, short
      duration of coma after resuscitation, and when the studies are performed within
      the first few days. In patients who remain in coma days after resuscitation and
      lack appropriate brainstem reflexes, however, even the most normal appearing
      electrophysiologic patterns do little to change the overall prognosis. Aside from
      prognostication, electrophysiologic testing holds great promise in defining the
      basic anatomy and physiology of coma emergence after cardiac arrest. In addition,
      quantitative EEG and automated evoked potentials have the potential to render
      these tools less subjective and arcane and more applicable for monitoring
      patients in the period during and immediately after resuscitation. Quantitative
      EEG also has great potential asa tool to define the time window for
      neuroprotective intervention and the means to track the response to such
      therapies in real time.

PMID- 16443133
TI  - Neuroimaging and serologic markers of neurologic injury after cardiac arrest.
AB  - Determining prognosis in the setting of hypoxic-ischemic injury following cardiac
      arrest is difficult based solely on clinical parameters in the patient who is
      critically ill. The article discusses bio- chemical markers in the blood and in
      the cerebrospinal fluid that are evaluated for prognostic information, along with
      radiologic indicators of anoxic cerebral damage. It includes a recommended
      algorithm using a combination of serologic and radiologic markers of cerebral
      injury for assessing prognosis in the patient who is comatose following cardiac
      arrest.

PMID- 16443134
TI  - Movement disorders after resuscitation from cardiac arrest.
AB  - It is difficult to predict precisely the final neurologic outcome from cardiac
      arrest and accompanying cerebral hypoxia. Although rare, several movement
      disorders may arise as a consequence of hypoxic injury, including myoclonus,
      dystonia, akinetic-rigid syndromes, tremor, and chorea. Dys-function of various
      portions of the central nervous system, including the basal ganglia, thalamus,
      midbrain, and cerebellum, is implicated in the pathogenesis of these posthypoxic
      movement disorders. The development of animal models of posthypoxic movement
      disorders and of newer imaging techniques applied to human patients who have
      movement disorders after hypoxic episodes has improved understanding of the
      pathophysiology of posthypoxic movement disorders and has suggested newer
      treatments. Many outstanding questions remain, however. What factors promote
      susceptibility to the development of posthypoxic movement disorders? Why do
      patients who have similar clinical hypoxic insults develop markedly dis-similar
      movement disorders? Why are the basal ganglia especially vulnerable to cerebral
      hypoxia? Why do some movement disorders occur in delayed fashion and progress for
      years after the hypoxic insult? Is the pathogenesis of progressive posthypoxic
      movement disorders related to that of neurodegenerative diseases? What are the
      most effective medications for the various posthypoxic movement disorders? Is
      there a role for deep brain stimulation in the treatment of posthypoxic movement
      disorders? We anticipate that current and future research in the area of
      posthypoxic movement disorders will reveal answers to some of these important
      questions.

PMID- 16443136
TI  - Brain injury from cardiac arrest in children.
AB  - This article reviews the important differences between children and adults
      suffering brain injury following cardiac arrest. The differences in etiology,
      pathophysiology, neuronal vulnerability, and repair in the context of the
      developing brain are reviewed. The available clinical data are reviewed, and
      selected treatment priori-ties are declared. The article includes a discussion of
      knowledge gaps and future directions.

PMID- 16443135
TI  - Cognitive and neurobehavioral dysfunction after cardiac bypass procedures.
AB  - From a cognitive standpoint, CABG as currently practiced appears to be safe for
      the great majority of patients, but transient changes involving memory, executive
      functions, and motor speed may still occur in a subset of patients during the
      first few days to weeks after CABG. The etiology most likely is multifactorial
      and includes a synergistic effect of microemboli, hypo-perfusion, and other
      variables associated with major surgery. Older age and degree of pre-existing
      cerebrovascular disease have been identified as important risk factors. The short
      term cognitive changes appear to be reversible by 3 months after surgery for most
      patients. Late cognitive decline after CABG,occurring between 1 and 5 years after
      the surgery, has been well documented,but controlled studies demonstrating that
      this decline is specifically attributable to the use of cardiopulmonary bypass
      itself rather than to progression of underlying cerebrovascular disease or other
      age-related changes are pending.

PMID- 16443137
TI  - The declaration of death and the withdrawal of care in the neurologic patient.
AB  - Intensive care technologies have led to an increase in patients who are
      neurologically devastated and deceased. The practical, moral, and ethical
      situations encountered can be varied and challenging to manage. Decisions and
      discussions surrounding withdrawal of care, death by neurologic criteria, and
      organ donation require significant knowledge of the prognosis, ancillary testing,
      and definitions of these processes. Experience and skill are often required on
      the part of physicians and staff to guide families through these most difficult
      of circumstances.

PMID- 16443140
TI  - Respiratory physiologic changes in pregnancy.
AB  - In summary, the major physiologic changes that occur in pregnancy are the
      increased minute ventilation, which is caused by increased respiratory center
      sensitivity and drive; a compensated respiratory alkalosis; and a low expiratory
      reserve volume. The vital capacity and measures of forced expiration are well
      preserved. Patients who have many lung diseases tolerate pregnancy well, with the
      exception of those who have pulmonary hypertension or chronic respiratory
      insufficiency from parenchymal or neuromuscular disease.

PMID- 16443141
TI  - Safety of asthma and allergy medications in pregnancy.
AB  - Given the unique nature of pregnancy with respect to obtaining safety data
      regarding medication exposures, developing comprehensive information on the wide
      variety of medications that might be of clinical benefit during pregnancy is a
      challenging and on-going task. For many of the most commonly used asthma and
      allergy medications that were covered in this article, there is at least limited
      human data are available. Even for relatively well-studied medications, there are
      many unanswered questions, and few studies exist that are large enough to rule
      out at least a doubling of risk for specific outcomes, particularly congenital
      anomalies. This challenge becomes even more daunting when evaluating risks of
      individual products is considered the optimal goal, as opposed to "lumping" all
      medication exposures within a class. All of these issues call for more human
      pregnancy data that are collected more efficiently so that the answers that
      clinicians and pregnant women need are available more readily. In the meantime,
      health care providers and pregnant women must work with the information that is
      available to evaluate the risks and benefits of a particular medication and
      alternative choices for treatment of asthma or allergy during pregnancy, while
      considering the potential for adverse effects if the woman with severe or
      uncontrolled asthma is under-treated. To assist in making a risk/benefit
      assessment, the clinician can draw on existing resources that provide systematic
      periodic review of new data on medications in pregnancy as it becomes available,
      and synthesize the entire body of data on a particular drug into concise summary
      statements. Two such resources are TERIS (TeratogenInformation System) [38] and
      Reprotox [39]; both on-line services are managed by experts in the field of
      teratology. An additional resource for clinicians and pregnant women is the
      Organization of Teratology Information Specialists [40], a network of risk
      assessment counselors in the United States and Canada who specialize in research
      and the communication of risks that are associated with exposures in pregnancy.

PMID- 16443142
TI  - The epidemiology of asthma during pregnancy: prevalence, diagnosis, and symptoms.
AB  - We demonstrated that asthma remains a common condition among pregnant women and
      that the prevalence of self-reported asthma in the United States is between 8.4%
      and 8.8%. In addition, approximately 4.1% of all pregnant women experienced an
      asthma attack in the previous year. Prevalence rates in other countries seem to
      be higher or substantially lower; however, further characterization of
      international trends using nationally representative data is needed. Data from a
      large prospective cohort study in the northeastern United States and national
      data demonstrate continued opportunities for population-level improvement in well
      managed asthma during pregnancy. Finally, asthma diagnosis and asthma control
      seem to differ by population characteristics (eg, age, race/ethnicity, socio
      economic status), and further research and clinical involvement are needed to ad
      dress potentially systematic variation in reporting and management of the
      disease.

PMID- 16443144
TI  - Outcomes of pregnancy in asthmatic women.
AB  - Mild and moderate asthma can be associated with excellent maternal and perinatal
      pregnancy outcomes, especially if patients are managed according to contemporary
      NAEPP recommendations. Severe and poorly controlled asthma may be associated with
      increased mild prematurity (<37 weeks' gestation), a need for cesarean delivery,
      preeclampsia, and growth restriction. Poorly controlled asthma and severe asthma
      exacerbations can result in maternal morbidity and mortality, which can have
      commensurate adverse pregnancy outcomes.

PMID- 16443143
TI  - The effect of pregnancy on the course of asthma.
AB  - The course of asthma is changed by pregnancy in variable ways for unknown
      reasons. Although the prospective studies used different criteria to stratify the
      severity of the patients' asthma, their conclusions were remarkably similar. Over
      all, an equal number of women have asthma symptoms that improve, worsen, or are
      unchanged through pregnancy. Asthma symptoms can worsen during pregnancy because
      of identifiable factors, such as infection, gastroesophageal re-flux disease,
      reduction of appropriate medications by physician or patient, and smoking.
      Undertreatment, which remains a problem during pregnancy, can lead to continued
      difficulty with asthma. Severe asthmatics tend to have increased symptoms
      compared with mild asthmatics. If symptoms worsen, it usually occurs in the
      second and third trimesters, with the peak in the sixth month. Generally, there
      is improvement in asthma in the last 4 weeks of pregnancy. During labor and
      delivery, only 10% to 20% of asthmatics have symptoms;severe asthmatics are more
      likely to have exacerbations. Asthma tends to return to the prepregnancy state
      within 3 months post partum. Successive pregnancies tend to have a similar course
      in each individual. Every asthmatic woman should be maintained on appropriate
      medications and followed carefully throughout pregnancy, especially in the second
      and third trimesters. Asthma specialists should be available for collaborative
      care when asthma is uncontrolled, or if there is an exacerbation. A timely
      adjustment in treatment for any changes in asthma course that might occur ensures
      the best control of the disease in the face of complex multiple influences.

PMID- 16443145
TI  - Current guidelines for the management of asthma during pregnancy.
AB  - Over the past few years, much has been learned that is relevant to the management
      of asthma in pregnancy. Although the studies that were reviewed here in provide
      more insight into the mechanisms that are involved and the treatment of asthma
      during pregnancy, there are more questions to be answered. It is hoped that the
      updated guidelines, which address the safety of contemporary asthma medications
      during pregnancy, will be a helpful resource in the treatment of our pregnant
      asthmatic patients.

PMID- 16443146
TI  - Acute asthma during pregnancy.
AB  - In addition to preventing maternal and fetal hypoxia, the goals of treating acute
      asthma exacerbation during pregnancy mirror those in the nongravid patient: rapid
      reversal of airflow obstruction with aerosolized bronchodilators,reduction of
      likelihood of recurrence by the addition of corticosteroids, and ongoing
      assessment of mother and fetus. Disposition decisions are multifaceted and must
      take into account the health and well-being of the pregnant patient and that of
      her fetus. Discharge planning includes prescription of scheduled 3-2 agonist
      treatments until symptoms resolve, intensification of daily treatment as needed,
      prescriptions for systemic and ICSs, as well provision of patient education, a
      personalized action plan, and close follow-up.

PMID- 16443147
TI  - Pregnancy rhinitis.
AB  - Pregnancy rhinitis has gained attention as a defined clinical entity that is
      recognized increasingly by medical professionals and by the public. It affects
      one in five pregnant women, and as far as we know, it is not caused by one single
      factor. Pregnant women should be informed about this cause of nasal congestion,
      and how to handle it. There is no cure known, but symptomatic treatment may be
      needed, because impaired nasal breathing can reduce quality of life and possibly
      affect the fetus. Simple measures, such as elevated head end of the bed, physical
      exercise, nasal saline washings, and nasal alar dilation can improve nasal
      breathing.

PMID- 16443148
TI  - The diagnosis and treatment of allergic rhinitis during pregnancy and lactation.
AB  - Rhinitis, including allergic rhinitis, in pregnancy represents a challenge to the
      physician in terms of its diagnosis and therapy. Although several unique in
      fluences of pregnancy adversely affect nasal mucosa, there is growing recognition
      that most symptomatic nasal problems are expressions of diagnostic entities that
      have been or will be experienced by the patient in the nonpregnant state. In
      approaching gestational rhinitis, emphasis should be placed on making an early,
      accurate diagnosis so that limited, specific, and informed medicinal intervention
      can be used. Simultaneously, the physician should keep in mind that
      rhinosinusitis in pregnancy is not necessarily a benign clinical problem. It is
      important to remember that upper airway disease, if uncontrolled, has a
      significant adverse effect on quality of life and may exacerbate coexisting
      asthma, which could affect the pregnancy outcome adversely [82]. Specialty
      consultation with otolaryngology or allergy may be necessary in the symptomatic
      pregnant woman before an accurate diagnosis and successful therapeutic
      recommendations can be made. The medico-legal atmosphere in the United States
      poses problems in making clinical statements about the absolute safety of
      medicinal intervention during pregnancy. For physicians who choose to take up
      this therapeutic challenge,suitable pharmacologic agents are available to manage
      the pregnant patient who has rhinitis or rhinosinusitis to achieve the desired
      therapeutic outcome. Suggested guidelines for the treatment of allergic
      conjunctivitis and rhinitis are summarized in Box 2. In the individual clinical
      situation, management decisions must be made only after establishing an exact
      clinical diagnosis, giving full consideration to the therapeutic risks, benefits,
      and alternatives, and documenting this in the patient's record. Moreover, the
      physician's interpretation of the benefit-risk ratio and the therapeutic
      decisions based thereon must be fully explained to, and approved by, the pregnant
      patient before intervention is initiated.A significant number of women who suffer
      from rhinitis of pregnancy are allergic. Under these circumstances, the best
      first-line approach is avoidance of allergens, which can reduce symptoms
      significantly. Often, what is chosen first is either a medication or the decision
      to allow the pregnant patient to suffer the symptoms, which can affect the
      pregnancy outcome adversely. Limited allergy consultation can be useful under
      these circumstances to identify pertinent allergens and to direct avoidance
      effectively. If avoidance is unsuccessful, then,with the informed consent of the
      patient and documentation in the chart, medicinal intervention can begin as shown
      (see Box 2). Although many women and caregivers may choose not to intervene with
      medications based on fear of teratogenicity, such notions are contradicted by a
      significant amount of medical evidence. This is especially true of drug
      intervention for rhinitis and rhinosinusitis after the first trimester.

PMID- 16443149
TI  - The management of respiratory infections during pregnancy.
AB  - Respiratory infections that complicate pregnancy are encountered frequently, and
      they encompass a broad range of disorders. Although respiratory infections
      usually are not seen more commonly in pregnancy, they often result in greater
      morbidity and mortality secondary to the physiologic adaptations that occur
      during pregnancy. Pregnant patients who have one of these disorders require
      higher level of surveillance and intervention.

PMID- 16443151
TI  - Role of cytochrome P450 in phospholipase A2- and arachidonic acid-mediated
      cytotoxicity.
AB  - Phospholipases A2 (PLA2) comprise a set of extracellular and intracellular
      enzymes that catalyze the hydrolysis of the sn-2 fatty acyl bond of phospholipids
      to yield fatty acids and lysophospholipids. The PLA2 reaction is the primary
      pathway through which arachidonic acid (AA) is released from phospholipids. PLA2s
      have an important role in cellular death that occurs via necrosis or apoptosis.
      Several reports support the hypothesis that unesterified arachidonic acid in
      cells is a signal for the induction of apoptosis. However, most of the biological
      effects of arachidonic acid are attributable to its metabolism by mainly three
      different groups of enzymes: cytochromes P450, cyclooxygenases, and
      lipoxygenases. In this review we will focus on the role of cytochrome P450 in AA
      metabolism and toxicity. The major pathways of arachidonic acid metabolism
      catalyzed by cytochrome P450 generate metabolites that are subdivided into two
      groups: the epoxyeicosatrienoic acids, formed by CYP epoxygenases, and the
      arachidonic acid derivatives that are hydroxylated at or near the omega-terminus
      by CYP omega-oxidases. In addition, autoxidation of AA by cytochrome P450-derived
      reactive oxygen species produces lipid hydroperoxides as primary oxidation
      products. In some cellular models of toxicity, cytochrome P450 activity
      exacerbates PLA2- and AA-dependent injury, mainly through the production of
      oxygen radicals that promote lipid peroxidation or production of metabolites that
      alter Ca2+ homeostasis. In contrast, in other situations, cytochrome P450
      metabolism of AA is protective, mainly by lowering levels of unesterified AA and
      by production of metabolites that activate antiapoptotic pathways. Several lines
      of evidence point to the combined action of phospholipase A2 and cytochrome P450
      as central in the mechanism of cellular injury in several human diseases, such as
      alcoholic liver disease and myocardial reperfusion injury. Inhibition of specific
      PLA2 and cytochrome P450 isoforms may represent novel therapeutic strategies
      against these diseases.

PMID- 16443152
TI  - Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral
      ischemia.
AB  - Ischemic stroke is caused by obstruction of blood flow to the brain, resulting in
      energy failure that initiates a complex series of metabolic events, ultimately
      causing neuronal death. One such critical metabolic event is the activation of
      phospholipase A2 (PLA2), resulting in hydrolysis of membrane phospholipids and
      release of free fatty acids including arachidonic acid, a metabolic precursor for
      important cell-signaling eicosanoids. PLA2 enzymes have been classified as
      calcium-dependent cytosolic (cPLA2) and secretory (sPLA2) and calcium-independent
      (iPLA2) forms. Cardiolipin hydrolysis by mitochondrial sPLA2 disrupts the
      mitochondrial respiratory chain and increases production of reactive oxygen
      species (ROS). Oxidative metabolism of arachidonic acid also generates ROS. These
      two processes contribute to formation of lipid peroxides, which degrade to
      reactive aldehyde products (malondialdehyde, 4-hydroxynonenal, and acrolein) that
      covalently bind to proteins/nucleic acids, altering their function and causing
      cellular damage. Activation of PLA2 in cerebral ischemia has been shown while
      other studies have separately demonstrated increased lipid peroxidation. To the
      best of our knowledge no study has directly shown the role of PLA2 in lipid
      peroxidation in cerebral ischemia. To date, there are very limited data on PLA2
      protein by Western blotting after cerebral ischemia, though some
      immunohistochemical studies (for cPLA2 and sPLA2) have been reported. Dissecting
      the contribution of PLA2 to lipid peroxidation in cerebral ischemia is
      challenging due to multiple forms of PLA2, cardiolipin hydrolysis, diverse
      sources of ROS arising from arachidonic acid metabolism, catecholamine
      autoxidation, xanthine oxidase activity, mitochondrial dysfunction, activated
      neutrophils coupled with NADPH oxidase activity, and lack of specific inhibitors.
      Although increased activity and expression of various PLA2 isoforms have been
      demonstrated in stroke, more studies are needed to clarify the cellular origin
      and localization of these isoforms in the brain, their responses in cerebral
      ischemic injury, and their role in oxidative stress.

PMID- 16443153
TI  - Free radicals, mitochondria, and hypoxia-ischemia in the developing brain.
AB  - The immature brain is particularly susceptible to free radical injury because of
      its poorly developed scavenging systems and high availability of iron for the
      catalytic formation of free radicals. Neurons are more vulnerable to free radical
      damage than glial cells, but oligodendrocyte progenitors and immature
      oligodendrocytes in very prematurely born infants are selectively vulnerable to
      depletion of antioxidants and free radical attack. Reactive oxygen and nitrogen
      species play important roles in the initiation of apoptotic mechanisms and in
      mitochondrial permeability transition, and therefore constitute important targets
      for therapeutic intervention. Oxidative stress is an early feature after cerebral
      ischemia and experimental studies targeting the formation of free radicals
      demonstrate various degrees of protection after perinatal insults. Oxidative
      stress-regulated release of proapoptotic factors from mitochondria appears to
      play a much more important role in the immature brain. This review will summarize
      and compare with the adult brain some of the current knowledge of free radical
      formation in the developing brain and its roles in the pathophysiology after
      cerebral hypoxia-ischemia.

PMID- 16443154
TI  - The role of oxidative stress in adult critical care.
AB  - Oxidative stress defines an imbalance in production of oxidizing chemical species
      and their effective removal by protective antioxidants and scavenger enzymes.
      Evidence of massive oxidative stress is well established in adult critical
      illnesses characterized by tissue ischemia-reperfusion injury and by an intense
      systemic inflammatory response such as during sepsis and acute respiratory
      distress syndrome. Oxidative stress could exacerbate organ injury and thus
      overall clinical outcome. We searched MEDLINE databases (January 1966 to June
      2005). For interventional studies, we accepted only randomized trials. Several
      small clinical trials have been performed in order to reduce oxidative stress by
      supplementation of antioxidants alone or in combination with standard therapies.
      These studies have reported controversial results. Newer large multicenter trials
      with antioxidant supplementation should be performed, considering administration
      at an early stage of illness and a wider population of critically ill patients.

PMID- 16443155
TI  - Cycloimide bacteriochlorin p derivatives: photodynamic properties and cellular
      and tissue distribution.
AB  - Reactive oxygen species generated by photosensitizers are efficacious remedy for
      tumor eradication. Eleven cycloimide derivatives of bacteriochlorin p (CIBCs)
      with different N-substituents at the fused imide ring and various substituents
      replacing the 3-acetyl group were evaluated as photosensitizers with special
      emphasis on structure-activity relationships. The studied CIBCs absorb light
      within a tissue transparency window (780-830 nm) and possess high photostability
      at prolonged light irradiation. The most active derivatives are 300-fold more
      phototoxic toward HeLa and A549 cells than the clinically used photosensitizer
      Photogem due to the substituents that improve intracellular accumulation
      (distribution ratio of 8-13) and provide efficient photoinduced singlet oxygen
      generation (quantum yields of 0.54-0.57). The substituents predefine selective
      CIBC targeting to lipid droplets, Golgi apparatus, and lysosomes or provide mixed
      lipid droplets and Golgi apparatus localization in cancer cells. Lipid droplets
      and Golgi apparatus are critically sensitive to photoinduced damage. The average
      lethal dose of CIBC-generated singlet oxygen per volume unit of cell was
      estimated to be 0.22 mM. Confocal fluorescence analysis of tissue sections of
      tumor-bearing mice revealed the features of tissue distribution of selected CIBCs
      and, in particular, their ability to accumulate in tumor nodules and surrounding
      connective tissues. Considering the short-range action of singlet oxygen, these
      properties of CIBCs are prerequisite to efficient antitumor photodynamic therapy.

PMID- 16443156
TI  - Nimesulide-induced hepatic mitochondrial injury in heterozygous Sod2(+/-) mice.
AB  - Nimesulide, a preferential COX-2 inhibitor, has been associated with rare
      idiosyncratic hepatotoxicity. The underlying mechanisms of liver injury are
      unknown, but experimental evidence has identified oxidative stress as a potential
      hazard and mitochondria as a target. The aim of this study was to explore whether
      genetic mitochondrial abnormalities, resulting in impaired mitochondrial function
      and mildly increased oxidative stress, might sensitize mice to the hepatic
      adverse effects of nimesulide. We used heterozygous superoxide dismutase 2
      (Sod2(+/-)) mice as a model, as these mice develop clinically silent
      mitochondrial stress but otherwise appear normal. Nimesulide was administered for
      4 weeks (10 mg/kg, ip, bid), at a dose equivalent to human therapeutic dosage. We
      found that the drug potentiated hepatic mitochondrial oxidative injury (decreased
      aconitase activity, increased protein carbonyls) in Sod2(+/-), but not wild-type,
      mice. Furthermore, the nimesulide-treated mutant mice exhibited increased hepatic
      cytosolic levels of cytochrome c and caspase-3 activity, as well as increased
      numbers of apoptotic hepatocytes. Finally, nimesulide in vitro caused a
      concentration-dependent net increase in superoxide anion in mitochondria from
      Sod2(+/-), but not Sod2(+/+) mice. In conclusion, repeated administration of
      nimesulide can superimpose an oxidant stress, potentiate mitochondrial damage,
      and activate proapoptotic factors in mice with genetically compromised
      mitochondrial function.

PMID- 16443157
TI  - Protein oxidation in plant mitochondria detected as oxidized tryptophan.
AB  - The formation of N-formylkynurenine by dioxygenation of tryptophan was detected
      in peptides from rice leaf and potato tuber mitochondria. Proteins in matrix and
      membrane fractions were separated by two-dimensional gel electrophoresis and
      identified using a Q-TOF mass spectrometer. N-Formylkynurenine was detected in 29
      peptides representing 17 different proteins. With one exception, the oxidation
      sensitive aconitase, all of these proteins were either redox active themselves or
      subunits in redox-active enzyme complexes. The same site was modified in (i)
      several adjacent spots containing the P protein of the glycine decarboxylase
      complex, (ii) two different isoforms of the mitochondrial processing peptidase in
      complex III, and (iii) the same tryptophan residues in Mn-superoxide dismutase in
      both rice and potato mitochondria. This indicates that Trp oxidation is a
      selective process.

PMID- 16443158
TI  - Free zinc inhibits transport of vitamin C in differentiated HL-60 cells during
      respiratory burst.
AB  - Zinc is an essential trace element for the immune system. It is known to be
      essential for highly proliferating cells, especially for cells of the immune
      system. However, zinc and other divalent cations are known to inhibit the human
      neutrophilic NADPH oxidase. Differentiated HL-60 cells were found to accumulate
      large quantities of vitamin C (ascorbate) after activation of the NADPH oxidase
      by phorbol esters (PMA). This increase in vitamin C transport is due to the
      generation of superoxide and subsequent oxidation of ascorbate to
      dehydroascorbate (DHA) which is preferentially taken up by the cells. We found
      that zinc reversibly inhibits both PMA-stimulated ascorbate uptake and superoxide
      generation with a half-maximal effect at 20 microM of free zinc ions. Higher
      residual extracellular ascorbate concentrations were measured with increasing
      zinc concentrations, indicating that less ascorbate was oxidized and taken up by
      the cells. When the fluorescent dye diSC3(5) was used to monitor shifts in
      membrane potential, we found that depolarization with PMA was prolonged after
      preincubation of the cells with zinc. Suppression of the respiratory burst as
      well as inhibition of the uptake of the antioxidant vitamin C may disturb the
      balance between oxidative damage of invading particles and antioxidant protection
      in activated neutrophils.

PMID- 16443160
TI  - Crystal structure of nitrated human manganese superoxide dismutase: mechanism of
      inactivation.
AB  - A cellular consequence of the reaction of superoxide and nitric oxide is enhanced
      peroxynitrite levels. Reaction of peroxynitrite with manganese superoxide
      dismutase (MnSOD) causes nitration of the active-site residue Tyr34 and nearly
      complete inhibition of catalysis. We report the crystal structures at 2.4 A
      resolution of human MnSOD nitrated by peroxynitrite and the unmodified MnSOD. A
      comparison of these structures showed no significant conformational changes of
      active-site residues or solvent displacement. The side chain of 3-nitrotyrosine
      34 had a single conformation that extended toward the manganese with O1 of the
      nitro group within hydrogen-bonding distance (3.1 A) of Nepsilon2 of the second
      shell ligand Gln143. Also, nitration of Tyr34 caused a weakening, as evidenced by
      the lengthening, of a hydrogen bond between its phenolic OH and Gln143, part of
      an extensive hydrogen-bond network in the active site. Inhibition of catalysis
      can be attributed to a steric effect of 3-nitrotyrosine 34 that impedes substrate
      access and binding, and alteration of the hydrogen-bond network that supports
      proton transfer in catalysis. It is also possible that an electrostatic effect of
      the nitro group has altered the finely tuned redox potential necessary for
      efficient catalysis, although the redox potential of nitrated MnSOD has not been
      measured.

PMID- 16443159
TI  - Altered iron homeostasis involvement in arsenite-mediated cell transformation.
AB  - Chronic exposure to low doses of arsenite causes transformation of human
      osteogenic sarcoma (HOS) cells. Although oxidative stress is considered important
      in arsenite-induced cell transformation, the molecular and cellular mechanisms by
      which arsenite transforms human cells are still unknown. In the present study, we
      investigated whether altered iron homeostasis, known to affect cellular oxidative
      stress, can contribute to the arsenite-mediated cell transformation. Using
      arsenite-induced HOS cell transformation as a model, it was found that total iron
      levels are significantly higher in transformed HOS cells in comparison to
      parental control HOS cells. Under normal iron metabolism conditions, iron
      homeostasis is tightly controlled by inverse regulation of ferritin and
      transferrin receptor (TfR) through iron regulatory proteins (IRP). Increased iron
      levels in arsenite transformed cells should theoretically lead to higher ferritin
      and lower TfR in these cells than in controls. However, the results showed that
      both ferritin and TfR are decreased, apparently through two different mechanisms.
      A lower ferritin level in cytoplasm was due to the decreased mRNA in the arsenite
      transformed HOS cells, while the decline in TfR was due to a lowered IRP-binding
      activity. By challenging cells with iron, it was further established that
      arsenite-transformed HOS cells are less responsive to iron treatment than control
      HOS cells, which allows accumulation of iron in the transformed cells, as
      exemplified by significantly lower ferritin induction. On the other hand, caffeic
      acid phenethyl ester (CAPE), an antioxidant previously shown to suppress As
      mediated cell transformation, prevents As-mediated ferritin depletion. In
      conclusion, our results suggest that altered iron homeostasis contributes to
      arsenite-induced oxidative stress and, thus, may be involved in arsenite-mediated
      cell transformation.

PMID- 16443161
TI  - A sensitive method for the quantitative measurement of protein thiol modification
      in response to oxidative stress.
AB  - The combination of proteomics with highly specific and sensitive affinity
      techniques is important for the identification of posttranslational modifications
      by reactive oxygen and nitrogen species (ROS/RNS). One of the most pressing
      problems with this approach is to determine accurately the extent of modification
      of specific amino acids, such as cysteine residues, in a complex protein sample.
      A number of techniques relevant to free radical biology use biotin tagging as a
      method to follow protein modification with high sensitivity and specificity. To
      realize the potential of this approach to provide quantitative data, we have
      prepared a series of biotinylated proteins through the modification of lysine
      residues. These proteins were then used as quantitative standards in
      electrophoretic separation of protein samples labeled with biotin-conjugated
      iodoacetamide. The utility of the approach was assessed by measuring modification
      of thiols in response to exposure to thiol oxidants, as well as the amount of
      protein adduct formation with a biotin-tagged electrophilic lipid. Furthermore,
      using a combination of native and biotin-tagged cytochrome c, this method was
      used to quantitate the amount of thiol relative to the amount of protein in a
      given spot on a two-dimensional gel. Thus, we have developed a versatile, cost
      effective standard that can be used in proteomic methods to quantitate biotin
      tags in response to oxidative stress.

PMID- 16443162
TI  - Ischemic preconditioning requires increases in reactive oxygen release
      independent of mitochondrial K+ channel activity.
AB  - Mitochondrial ATP-sensitive K+ channels (mitoKATP) mediate ischemic
      preconditioning, a cardioprotective procedure. MitoKATP activity has been
      proposed to either enhance or prevent the release of reactive oxygen species.
      This study tested the redox effects of mitoKATP in order to clarify the role of
      these channels during preconditioning. We found no evidence that mitoKATP
      channels increase mitochondrial reactive oxygen species release directly. In
      addition, neither ischemic preconditioning nor the mitoKATP agonist diazoxide
      increased antioxidant defenses. Furthermore, increases in reactive oxygen species
      observed during ischemic preconditioning were not inhibited by mitoKATP
      antagonists, suggesting that they occur upstream of channel activity.
      Antioxidants were tested to verify if diazoxide-promoted ischemic protection was
      dependent on reactive oxygen species. N-Acetylcysteine proved to be an inadequate
      antioxidant for these tests since it directly interfered with the ability of
      diazoxide to activate mitoKATP. Catalase reversed the beneficial effect of
      preconditioning, but not of diazoxide, indicating that reactive oxygen species
      mediating preconditioning occur upstream of mitoKATP. Taken together, these
      results demonstrate that ischemic preconditioning increases reactive oxygen
      release independently of mitoKATP and suggest that the activity of this channel
      prevents oxidative reperfusion damage by decreasing reactive oxygen species
      production.

PMID- 16443163
TI  - Effect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial
      electron transport chain, antioxidative defenses, and life span of mice.
AB  - The main purpose of this study was to determine whether intake of coenzyme Q10,
      which can potentially act as both an antioxidant and a prooxidant, has an impact
      on indicators of oxidative stress and the aging process. Mice were fed diets
      providing daily supplements of 0, 93, or 371 mg CoQ10 /kg body weight, starting
      at 3.5 months of age. Effects on mitochondrial superoxide generation, activities
      of oxidoreductases, protein oxidative damage, glutathione redox state, and life
      span of male mice were determined. Amounts of CoQ9 and CoQ10, measured after 3.5
      or 17.5 months of intake, in homogenates and mitochondria of liver, heart,
      kidney, skeletal muscle, and brain increased with the dosage and duration of
      CoQ10 intake in all the tissues except brain. Activities of mitochondrial
      electron transport chain oxidoreductases, rates of mitochondrial O2-* generation,
      state 3 respiration, carbonyl content, glutathione redox state of tissues, and
      activities of superoxide dismutase, catalase, and glutathione peroxidase,
      determined at 19 or 25 months of age, were unaffected by CoQ10 administration.
      Life span studies, conducted on 50 mice in each group, showed that CoQ10
      administration had no effect on mortality. Altogether, the results indicated that
      contrary to the historical view, supplemental intake of CoQ10 elevates the
      endogenous content of both CoQ9 and CoQ10, but has no discernable effect on the
      main antioxidant defenses or prooxidant generation in most tissues, and has no
      impact on the life span of mice.

PMID- 16443164
TI  - Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor
      uptake.
AB  - We recently reported that methionine-loaded human umbilical vein endothelial
      cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl
      radical generation and oxidation of lipids in LDL. Herein we have analysed the
      Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been
      characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC
      with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL
      uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs
      in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with
      cardiovascular disease (CVD). While reagent Hcy (< 50 microM) promoted copper
      catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs
      promoted LDL protein nitration. In addition, LDL nitration was associated with
      enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein
      nitration and uptake by monocytes, but not carbonyl formation, was elevated in
      both RA and OA patients with CVD compared with disease-matched patients that had
      no evidence of CVD. Moreover, a direct correlation between plasma total Hcy
      (tHcy) and LDL uptake was observed. The present studies suggest that elevated
      plasma tHcy may promote LDL nitration and increased scavenger receptor uptake,
      providing a molecular mechanism that may contribute to the clinical link between
      CVD and elevated plasma tHcy.

PMID- 16443166
TI  - Immuno-spin trapping of hemoglobin and myoglobin radicals derived from nitrite
      mediated oxidation.
AB  - The reaction of nitrite with hemoglobin has become of increasing interest due to
      the realization that plasma nitrite may act as an NO congener that is activated
      by interaction with red blood cells. Using a combination of spectrophotometry,
      immuno-spin trapping, and EPR, we have examined the formation of radicals during
      the oxidation of oxyhemoglobin (oxyHb) and oxymyoglobin (oxyMb) by inorganic
      nitrite. The proposed intermediacy of ferryl species during this oxidation was
      confirmed by spectrophotometry using multiple linear regression analysis of
      kinetic data. Using EPR/spin trapping, a protein radical was observed in the case
      of oxyMb, but not oxyHb, and was inhibited by catalase. When DMPO spin trapping
      was combined with Western blot analysis using an anti-DMPO-nitrone antibody,
      globin/DMPO adducts of both oxyHb and oxyMb were detected, and their formation
      was inhibited by catalase. Catalase effects confirm the intermediacy of hydrogen
      peroxide as a heme oxidant in this system. Spectrophotometric kinetic studies
      revealed that the presence of DMPO elongated the lag phase and decreased the
      maximal rate of oxidation of both oxyHb and oxyMb, which suggests that the globin
      radical plays an active role in the mechanism of autocatalysis. Interestingly,
      the oxidation of oxyHb or oxyMb by nitrite, but not by hydrogen peroxide,
      produced a diffusible radical that was able to generate spin adducts on a
      bystander protein. This indicates that the oxidation of oxyhemeproteins by
      nitrite may cause more widespread oxidative damage than the corresponding
      oxidation by hydrogen peroxide. The immuno-spin trapping technique represents an
      important new development for the study of the range and extent of protein
      oxidation by free radicals and oxidants.

PMID- 16443165
TI  - Nitric oxide as a cellular antioxidant: a little goes a long way.
AB  - Nitric oxide (NO*) is an effective chain-breaking antioxidant in free radical
      mediated lipid oxidation (LPO). It reacts rapidly with peroxyl radicals as a
      sacrificial chain-terminating antioxidant. The goal of this work was to determine
      the minimum threshold concentration of NO* required to inhibit Fe2+ -induced
      cellular lipid peroxidation. Using oxygen consumption as a measure of LPO, we
      simultaneously measured nitric oxide and oxygen concentrations with NO* and O2
      electrodes. Ferrous iron and dioxygen were used to initiate LPO in
      docosahexaenoic acid-enriched HL-60 and U937 cells. Bolus addition of NO* (1.5
      microM) inhibited LPO when the NO* concentration was greater than 50 nM.
      Similarly, using (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2
      diolate as a NO* donor we found that an average steady-state NO* concentration of
      at least 72 +/- 9 nM was required to blunt LPO. As long as the concentration of
      NO* was above 13 +/- 8 nM the inhibition was sustained. Once the concentration of
      NO* fell below this value, the rate of lipid oxidation accelerated as measured by
      the rate of oxygen consumption. Our model suggests that a continuous production
      of NO* that would yield a steady-state concentration of only 10-20 nM is capable
      of inhibiting Fe2+ -induced LPO.

PMID- 16443167
TI  - Modification of amino acid residues in human serum albumin by myeloperoxidase.
AB  - Myeloperoxidase is released from stimulated polymorphonuclear leukocytes at
      inflammatory loci. Besides its bactericidal activity, it interacts with human
      serum albumin that is essential for the endothelial uptake of myeloperoxidase and
      its contribution in regulation of the blood vessel tonus. Here, we investigated
      which kinds of modification dominate in the albumin protein by the
      myeloperoxidase-hydrogen peroxide system at physiological pH. In the presence of
      chloride, bromide, and nitrite, the myeloperoxidase-hydrogen peroxide system
      caused an oxidation, bromination, and nitrosylation/nitration of eight amino acid
      residues of albumin as detected by fragment analysis of tryptic digests with
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. An
      oxygen was incorporated into the methionines Met147, Met353, and Met572 as well
      as into the tryptophan Trp238. In the case of methionine residues, this oxygen
      was derived from the water phase as shown using 18O-enriched water.
      Nitrosylation/nitration was observed at the tryptophan Trp238 and the tyrosines
      Tyr162, Tyr425, and Tyr476 according to the mass shift of 29 Da and 45 Da. The
      incorporation of one or two bromines was found into the tyrosines Tyr425 and
      Tyr476. We did not observe any chlorination of albumin fragments. Thus,
      myeloperoxidase modifies in multiple ways amino acid residues in human serum
      albumin.

PMID- 16443169
TI  - Protein modification caused by a high dose of gamma irradiation in cryo
      sterilized plasma: protective effects of ascorbate.
AB  - Gamma irradiation is a method of pathogen inactivation in plasma derivatives
      currently under development. Gamma rays inactivate all known blood-borne viruses.
      However, the virucidally effective dose of radiation may affect the integrity and
      function of plasma proteins. Biological activity recoveries of the therapeutic
      products were shown to be significantly improved by lowering the irradiation
      temperature and by the addition of antioxidants; the mechanisms responsible for
      this have not been elucidated yet. Here we sterilized human plasma by gamma
      irradiation (50 kGy), on dry ice, in the presence (or absence) of ascorbate. The
      subsequent protein oxidation was quantified by a ferric-xylenol orange
      (hydroperoxides) and by DNPH-coupled assays (carbonyls). We demonstrated for the
      first time that irradiation of frozen plasma (without saturation with oxygen)
      resulted in the generation of protein hydroperoxides, the yield of which was
      dramatically decreased when plasma was irradiated in the presence of either
      sodium azide or ascorbate. In irradiated plasma the concentration of protein
      carbonyls was twofold higher than in nonirradiated control. Ascorbate
      significantly inhibited protein carbonylation. We concluded that freezing of
      plasma during irradiation does not provide the complete protection against
      protein carbonylation and hydroperoxide generation. Addition of ascorbate and
      some nontoxic metabolic inhibitors might be useful as protecting stabilizers.

PMID- 16443168
TI  - Curcumin and its analogues as potent inhibitors of low density lipoprotein
      oxidation: H-atom abstraction from the phenolic groups and possible involvement
      of the 4-hydroxy-3-methoxyphenyl groups.
AB  - Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a
      yellow ingredient isolated from turmeric (Curcumin longa). It has been shown to
      exhibit a variety of biological activities including antioxidative activity. In
      order to find more active antioxidants with 1 as the lead compound we synthesized
      curcumin analogues, i.e., 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione
      (2), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5
      dione (3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5
      dione (4), 1,7-bis (4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (5), 1-(3,4
      dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (6), 1,7
      bis(3,4-dimethoxyphenyl)-1,6- heptadiene-3,5-dione (7), 1,7-bis(4-methoxyphenyl)
      1,6-heptadiene-3,5-dione (8), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (9).
      Antioxidative effects of curcumin and its analogues against free radical
      initiated peroxidation of human low density lipoprotein (LDL) were studied. The
      peroxidation was initiated either by a water-soluble initiator 2,2'-azobis(2
      amidinopropane hydrochloride) (AAPH), or by cupric ion (Cu2+). The reaction
      kinetics were monitored either by the uptake of oxygen and the depletion of alpha
      tocopherol present in the native LDL, or by the formation of thiobarbituric acid
      reactive substances. Kinetic analysis of the antioxidation process demonstrates
      that these compounds, except 7, 8, and 9, are effective antioxidants against AAPH
      and Cu2+ -initiated LDL peroxidation by H-atom abstraction from the phenolic
      groups. Compounds 2 and 3 which bear ortho-diphenoxyl functionality possess
      significantly higher antioxidant activity than curcumin and other analogues, and
      the 4-hydroxy-3-methoxyphenyl group also play an important role in the
      antioxidative activity.

PMID- 16443170
TI  - Hypercapnia prevents neovascularization via nitrative stress.
AB  - Neovascularization after an ischemic insult is a beneficial attempt to salvage
      the injured tissue. Yet, despite the production of angiogenic factors within
      ischemic tissues, compensatory growth of new vessels fails to provide adequate
      vascularization. Thus, we hypothesized that local factors counter efficient
      revascularization. Whereas ischemia is often considered to be synonymous with an
      oxygen deficit, it is also associated with a concomitant local elevation of
      carbon dioxide (CO2). Although studies suggest that hypercapnia impacts tissue
      neovascularization, its significance relative to the abundantly described effects
      of hypoxia and its underlying mechanisms have yet to be elucidated. Therefore, we
      investigated the effects of hypercapnia on blood vessel growth in models of
      developmental and ischemic neovascularization. Acute and prolonged CO2 exposure
      inhibited developmental neovascularization of the rodent retina, as well as
      revascularization of the ischemic retina. Hypercapnia induced early increases in
      endothelial nitric oxide synthase and nitrative stress, associated with astrocyte
      impairment and endothelial cell death, as well as downregulation of the
      proangiogenic prostaglandin E2 receptor EP3. These results establish a previously
      unexplored means by which hypercapnia hinders efficient neovascularization, a
      mechanism that may contribute to ischemic tissue injury.

PMID- 16443172
TI  - Do indicators of maternal iron status reflect placental iron status at delivery?
AB  - Indicators of maternal iron (Fe) status were studied in relation to placental Fe
      (Pl-Fe) status. Placental (Pl) and maternal (M) venous blood samples were
      obtained from primiparous women (n = 38), with normal delivery at Paroissien
      Hospital, Argentina. Maternal hemoglobin (M Hb), soluble transferrin receptor (M
      sTfR) (ELISA) and serum ferritin (M S-Ft) were studied in relation to Pl-Fe,
      ferritin (Pl-Ft) and transferrin receptor (Pl-TfR). Pl-TfR was measured by dot
      blot assay, Pl-Ft and M S-Ft by immunoassay (IRMA) and Pl-Fe by atomic absorption
      spectrometry. Fe status indicators were, respectively, (mean +/- SD): M Hb 113 +/
      16 g/L; M S-Ft 36 +/- 42 microg/L; M sTfR 6.3 +/- 3.1 mg/L; Pl-Fe 170 +/- 56
      microg/g placenta; Pl-Ft 33 +/- 18 microg/g placenta; Pl-TfR 18 +/- 18 (range 0
      58) microg/g placenta. Pl-Fe, Pl-Ft and Pl-TfR did not correlate to M Hb, M S-Ft
      and M sTfR. Women with Pl- Fe, Pl-Ft and Pl-TfR above or below the corresponding
      median values did not show any statistical significant difference in M Hb, M sTfR
      or M S-Ft values. Pl-Ft concentration was lower in women with Hb < 110 g/L than
      in women with normal values: 26 +/- 13 vs. 38 +/- 20 microg/g, respectively (p =
      0.021). When Pl-TfR, Pl-Ft and Pl-Fe were compared in women with M S-Ft above or
      below the cut-off point of 10 or 20 microg/L, no significant difference was found
      for Pl-TfR neither for Pl-Ft nor Pl-Fe. These results suggest that maternal
      indicators of Fe status, particularly M sTfR and M S-Ft, do not reflect Fe status
      of the placenta at delivery.

PMID- 16443171
TI  - Mobilisation of recently absorbed 59Fe in ex vivo perfused rat duodena and the
      influence of iron status and subsequently absorbed chelators.
AB  - To investigate the effect of subsequently absorbed metal chelators on recently
      absorbed 59Fe, duodenal segments from iron-deficient and iron-adequate rats were
      perfused ex vivo until the 59Fe tissue load had reached a steady state.
      Subsequently, the segments were perfused with 3 model chelators and their iron
      complexes: nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA)
      and citrate. Of these, NTA and EDTA bind iron much tighter than citrate, and Fe
      NTA complexes exchange iron within seconds while Fe-EDTA complexes need 48 h to
      reach equilibrium. Duodenal mucosa-to-serosa transport rates were comparable for
      all 3 chelators and correlated linearly with luminal concentration. Subsequent
      perfusion with increasing NTA, Fe-NTA(1:2) and EDTA concentrations mobilised
      increasing amounts of 59Fe from the duodenum. Mobilised 59Fe moved preferentially
      back into the luminal perfusate in iron-adequate segments. In iron-deficient
      segments, 59Fe preferentially continued the absorption process across the
      basolateral membrane. Fe-EDTA(1:1) hardly mobilised any 59Fe back into the lumen,
      though basolateral transfer increased at high concentrations. Citrate and Fe
      citrate(1:1) mobilised 59Fe only at very high concentrations. This behaviour is
      in accordance with the rules of complex chemistry: strong, fast reacting ligands
      like NTA show most impact. Slowly reacting complexes like Fe-EDTA(1:1) have
      little mobilising impact in spite of strong affinity between EDTA and iron. The
      low affinity between iron and citrate can be compensated by large concentration.
      Moreover, iron-deficient segments show stronger re-uptake of mobilised 59Fe from
      the lumen and a stronger transfer of 59Fe from the tissue across the basolateral
      membrane. Both are compatible with the more marked expression of divalent metal
      transporter 1 (DMT-1) and IREG-1 at the brushborder and basolateral membrane of
      iron-deficient enterocytes. The data suggest that iron ions interact with food
      ligands during their passage from the apical to the basolateral side of duodenal
      enterocytes.

PMID- 16443173
TI  - Differences in plasma homocysteine levels between Zucker fatty and Zucker
      diabetic fatty rats following 3 weeks oral administration of organic vanadium
      compounds.
AB  - PURPOSE: Recently, our laboratory group has reported that rats with Type 1
      diabetes have decreased plasma homocysteine and cysteine levels compared to non
      diabetic controls and that organic vanadium treatment increased plasma
      homocysteine concentrations to non-diabetic concentrations. However, to date, no
      studies have been done investigating the effects of organic vanadium compounds on
      plasma homocysteine and its metabolites in Type 2 diabetic animal model. These
      studies examined the effect of organic vanadium compounds
      [bis(maltolato)oxovanadium(IV) and bis(ethylmaltolato)oxovanadium(IV); BMOV and
      BEOV] administered orally on plasma concentrations of homocysteine and its
      metabolites (cysteine and cysteinylglycine) in lean, Zucker fatty (ZF) and Zucker
      diabetic fatty (ZDF) rats. ZF rats are a model of pre-diabetic Type 2 diabetes
      characterized by hyperinsulinemia and normoglycemia. The ZDF rat is a model of
      Type 2 diabetes characterized by relative hypoinsulinemia and hyperglycemia.
      METHODS: Zucker lean and ZF rats received BMOV in the drinking water at a dose of
      0.19 +/- 0.02 mmol/kg/day. Lean and ZDF rats received BEOV by oral gavage daily
      at dose of 0.1 mmol/kg. The treatment period for both studies was 21 days. At
      termination, animals were fasted overnight (approximately 16 h) and blood samples
      were collected by cardiac puncture for determination of plasma glucose, insulin
      and homocysteine levels. Plasma homocysteine and its metabolites levels were
      determined using high-pressure liquid chromatography. Plasma glucose was
      determined using a Glucose Analyzer 2. Plasma insulin levels were determined by
      radioimmunoassay. Plasma triglycerides were determined by an enzymatic assay
      methodology. RESULTS: ZF (n = 4) and ZDF (n = 10) rats had significantly lower
      plasma homocysteine as compared to their respective lean groups (ZF 0.78 +/- 0.1
      micromol/L vs. Zucker lean 2.19 +/- 0.7 micromol/L; ZDF 1.71 +/- 0.2 micromol/L
      vs. Zucker lean 3.02 +/- 0.3 micromol/L; p < 0.05). BMOV treatment in ZF rats
      restored plasma homocysteine levels to those observed in lean untreated rats (ZF
      treated: 2.04 +/- 0.2 micromol/L; lean 2.19 +/- 0.7 micromol/L). There was a
      modest effect of BMOV treatment on plasma glucose levels in ZF rats. BEOV
      treatment significantly decreased the elevated plasma glucose levels in the ZDF
      rats (lean 7.9 +/- 0.1 mmol/L; lean + vanadium 7.7 +/- 0.2 mmol/L; ZDF 29.9 +/-
      0.4 mmol/L; ZDF + vanadium 17.4 +/- 0.3 mmol/L, p < 0.05). Organic vanadium
      treatment reduced cysteine levels in both ZF and ZDF rats. No differences in
      total plasma cysteinylglycine concentrations were observed. CONCLUSION: Plasma
      homocysteine levels are significantly reduced in a pre-diabetic model of Type 2
      diabetes, which was restored to lean levels upon vanadium treatment; however,
      this restoration of plasma homocysteine levels was not seen in ZDF Type 2
      diabetic rats following vanadium treatment. In the latter case vanadium treatment
      may not have totally overcome the insulin resistance seen in these animals.

PMID- 16443174
TI  - The effect of orally administered melatonin on tissue accumulation and toxicity
      of cadmium in mice.
AB  - The aim of this study was to determine whether an oral administration of
      melatonin, a known antioxidant, free radical scavenger and metal chelator,
      influences tissue accumulation and toxicity of cadmium (Cd) in mice exposed
      subchronically to the metal. The animals received drinking water containing 50
      microg Cd/mL only or with additional 2, 4 or 6 microg/mL melatonin for 8 weeks.
      Melatonin co-treatment brought about a dose-dependent decrease in the renal,
      hepatic and intestinal Cd concentrations, and the renal and hepatic
      metallothionein levels followed a pattern similar to that of the Cd accumulation.
      Histopathological changes occurred only in the kidneys (glomerular swelling and
      focal tubular degeneration) in all mice from the Cd alone group. In mice co
      treated with melatonin, only slight (2 microg/mL melatonin) or no damage (4 and 6
      microg/mL melatonin) was seen. The Cd and melatonin treatments did not affect
      renal lipid peroxidation and iron concentration. These data indicate that orally
      administered melatonin together with Cd reduces tissue accumulation of this
      metal; in particular, the reduction of renal Cd accumulation by melatonin is
      probably responsible for the prevention of Cd-induced injury in this organ.

PMID- 16443175
TI  - Aluminium-induced injury to kidney proximal tubular cells: Effects on markers of
      oxidative damage.
AB  - Aluminium (Al)-induced injury to various cells including brain and bone is well
      described. We have previously shown that Al initiated damage to kidney cells in
      culture assessed by loss of cell viability, enzyme release and damage to cell
      brush borders. However, little is known about the mechanism(s) of these effects,
      we therefore investigated whether lipid peroxidation and/or sulphydryl depletion,
      i.e. cellular glutathione (GSH) depletion, could be part of this process(es).
      Monolayers of porcine kidney proximal tubular cells (PTC), LLC-PK1, were either
      exposed to 100 micromol/L Al as a citrate complex or cis-platin (cis-Pt) or
      mercury (Hg) as damage mediating controls (positive), or no added metals
      (negative control). Malondialdehyde (MDA), a marker of lipid peroxidation,
      cellular GSH as the intracellular sulphydryl compound, heat shock protein 70
      (Hsp70), glutathione peroxidase (GPx) as a reactive oxygen species scavenger
      enzyme and cellular uptake of Al were assessed. MDA increased significantly (p =
      0.03) more than two-fold in the cell lysate after PTCs were exposed to Al for 48
      h. In Al-treated PTC, the GSH content of the cell lysate increased to 1.042 +/-
      0.080 mmol/L compared with the 0.80 +/- 0.1.64 mmol/L control value. The Hsp70
      content of the cells showed no significant change for Al (6.5% vs. 4.4% control
      value) and GPx activity increased slightly from 0.41 to 0.45 mU/mg protein.
      Treatment with cis-Pt and Hg also resulted in a significant increase in MDA and
      Hsp70 and reduction in cellular GSH and GPx activity. The low cellular Al uptake
      as well as some inherent insensitivity related to the cell type might be
      contributory factors for the small effect of Al on kidney cells and markers of
      oxidative damage.

PMID- 16443176
TI  - Influenza vaccination among children with asthma in medicaid managed care.
AB  - OBJECTIVE: To describe influenza vaccination rates and identify risk factors for
      missing vaccination among children with asthma in managed Medicaid. METHODS: As
      part of a longitudinal study of asthma care quality, parents of children aged 2
      16 years with asthma enrolled in Medicaid managed care organizations in
      Massachusetts, Washington, and California were surveyed by telephone at baseline
      and 1 year. We evaluated influenza vaccination rates during the follow-up year.
      RESULTS: The study population included 1058 children with asthma. The influenza
      vaccination rate was 16% among all children with asthma and 21% among those with
      persistent asthma. Children with persistent asthma (odds ratio [OR] 0.53, 95%
      confidence interval [CI] 0.36-0.79) and those who had been hospitalized during
      the follow-up year (OR 0.29, 95% CI 0.11-0.76) were less likely to miss
      vaccination. Children older than 9 years (OR 1.66, 95% CI 1.13-2.46) and children
      of parents with less than a high school education (OR 2.29, 95% CI 1.05-5.03),
      compared with a college degree, were at risk for missing vaccination. Among
      children with persistent asthma, older children (OR 1.65, 95% CI 1.01-2.69) and
      children of parents with less than a high school education (OR 4.13, 95% CI 1.43
      11.90) were more likely to miss influenza vaccination. CONCLUSIONS: Our findings
      suggest that interventions directed toward older children and families with lower
      educational levels may help improve influenza vaccination rates among this high
      risk group. The low overall vaccination rate highlights the need for improvement
      in this important component of asthma care quality for all children with asthma.

PMID- 16443177
TI  - At-home recovery following hospitalization for bronchiolitis.
AB  - OBJECTIVES: To characterize the at-home recovery of infants after hospitalization
      for bronchiolitis, the impact of recovery from this illness on the family, and
      the association between delayed infant recovery and parental satisfaction with
      hospital care. METHODS: Otherwise healthy infants less than 1 year of age
      admitted to 6 children's hospitals were eligible. Telephone interviews with 486
      parents (85% of sampled), 1-2 weeks following discharge, addressed functional
      recovery, lingering symptoms, family disruption, returns to the emergency
      department, and parental recall of satisfaction with care. RESULTS: Two thirds of
      infants experienced difficulties with normal routines (feeding, sleeping,
      contentedness, liveliness) on the day of discharge. By 5 days at home, 22%
      continued to experience disruption in sleeping, and 16% in feeding routines.
      Coughing (56%) and wheezing (27%) were common 4 to 6 days after discharge.
      Parents who reported longer delays in return to normal family routines took
      additional time off work, kept their infants out of day care twice as many days,
      and were more likely to take their infants to the doctor or hospital for repeat
      medical care. Parents from families slower to return to a normal routine recalled
      the hospital stay less favorably. CONCLUSIONS: A small but important proportion
      of infants have a protracted recovery period following hospitalization for
      bronchiolitis. Delayed recovery is associated with parental work time loss and
      less favorable parental impressions of care in the hospital. Anticipatory
      guidance about home recovery could allow parents to plan for extended home care
      and improve satisfaction with hospital care.

PMID- 16443179
TI  - How complete are immunization registries? The Philadelphia story.
AB  - OBJECTIVE: To assess accuracy and completeness of Philadelphia, Pa, registry data
      among children served by providers in areas at risk for underimmunization.
      METHODS: Philadelphia's Department of Public Health selected a simple random
      sample of 45 children age 19-35 months (or all children age 19-35 months if there
      were <45 children in the practice) from each of 30 private practices receiving
      government-funded vaccine and located in zip codes where children are at risk for
      underimmunization. Chart and registry data were compared with determine the
      proportion of children missing from the registry and assess differences in
      immunization coverage. RESULTS: Of 620 children reviewed, 567 (92%) were in the
      registry. Significant differences (P < .05) were observed in immunization
      coverage for 4 diphtheria-tetanus-acellular pertussis vaccinations, 3 polio
      vaccinations, 1 measles-mumps-rubella vaccination, and 3 Haemophilus influenzae
      type b vaccinations between the chart (80% coverage) and registry (62% coverage).
      Providers submitting electronic medical records or directly transferring
      electronic data to the registry had significantly more children in the registry
      and higher registry-reported immunization coverage than those whose data were
      entered from billing records or log forms. All practice types experienced
      difficulties in transferring complete data to the registry. CONCLUSIONS: Although
      92% of study children were in the registry, immunization coverage was
      significantly lower when registry data were compared with chart data. Because
      electronic medical records and direct electronic data transfer resulted in more
      complete registry data, these methods should be encouraged in linking providers
      with immunization registries.

PMID- 16443178
TI  - Predictors of hospital charges for children admitted with asthma.
AB  - OBJECTIVES: To examine patient and hospital characteristics associated with
      varying hospital charges for children admitted with asthma. METHODS: We conducted
      a retrospective cohort study of children (1-18 years old) hospitalized with
      asthma using data from the 2000 Kids' Inpatient Database (KID; n = 54,029).
      Predictors of interest included hospital type (teaching and children's hospitals)
      and patient characteristics (insurance type and race). RESULTS: After adjusting
      for patient and hospital characteristics, hospital charges were similar at
      teaching and nonteaching hospitals. Charges at children's hospitals were higher
      by 440 US dollars or 10% (95% CI, 352-528) compared with nonchildren's hospitals.
      Children with Medicaid had higher charges by 132 US dollars or 3% (95% CI, 57
      264) compared to those with private insurance. Compared to White children, Black
      children had higher charges by 396 US dollars or 10% (95% CI, 352-484), Hispanic
      children by 924 US dollars or 21% (95% CI, 880-1,012), and Asian children by 572
      US dollars or 13% (572 US dollars; 95% CI, 352-792). CONCLUSIONS: Important
      differences exist in the charges incurred by children with asthma based on
      patient and hospital characteristics. Efforts to understand the reasons behind
      the differences may help eliminate unnecessary variation in costs for asthma
      care.

PMID- 16443180
TI  - Does prenatal care at community-based health centers result in infant primary
      care at these sites?
AB  - OBJECTIVES: To describe where women receiving prenatal care (PNC) at community
      based health centers (CBHCs) go for infant primary care, and to assess reasons
      for and factors associated with leaving CBHCs and using other practices for
      infant care. METHODS: A prospective survey of women receiving PNC at CBHCs from
      February 2000 to February 2002 was conducted. In-person, prepartum, and
      postpartum surveys included questions about sociodemographic and health
      characteristics, and health services use. RESULTS: Among 1,107 primarily low
      income, African American mothers, 60% of women left CBHCs and used other
      practices for their infants due to dissatisfaction, inconvenience, referral to
      and perceived expertise at other sites, and insurance changes. Leaving CBHCs was
      associated with being white, Latina, US born, educated beyond high school,
      single, owning a car, using non-CBHC practices for prepregnancy care, and having
      child health insurance. Among those who left, 48% used hospital-based clinics
      (HBCs) and 52% used private practices (PPs). Mothers using HBCs, when compared to
      those using PPs, were more likely to be African American (AOR = 6.83; 95% CI:
      3.82, 12.22) or Latina (AOR = 5.60; 95% CI: 2.79, 11.24), dissatisfied with their
      PNC (AOR = 2.02; 95% CI: 1.05, 3.89) and to leave CBHCs because of insurance
      changes (AOR = 2.27; 95% CI: 1.18, 4.39) and perceived pediatric expertise at
      other sites (AOR = 4.81; 95% CI: 2.53, 9.11). CONCLUSIONS: The majority of women
      in our study left CBHCs and used other sites for pediatric care. Higher
      education, having child health insurance, and car ownership were associated with
      leaving CBHCs. Among women who left, race/ethnicity and perceived pediatric
      expertise were major factors associated with using HBCs rather than PPs.

PMID- 16443181
TI  - Maternal depressive symptoms are adversely associated with prevention practices
      and parenting behaviors for preschool children.
AB  - OBJECTIVE: To determine the relationship between maternal depressive symptoms and
      select prevention practices and parenting behaviors for older preschool children.
      METHODS: A telephone survey of mothers and female guardians of children entering
      kindergarten in Monroe County, New York, was administered to 400 eligible parents
      in 2001. The Mental Health Inventory-5 was used to determine maternal depressive
      symptoms. We examined the impact of maternal depression on well-child care,
      immunizations, routine dental care, tooth brushing, frequent reading, safe motor
      vehicle seating location, car seat or booster seat use, discipline consistency,
      and parenting confidence. RESULTS: A total of 17.7% of mothers had depressive
      symptoms, with increased rates among women who were poor, less educated, and
      single parents. Children of mothers with depressive symptoms were more likely to
      have not received routine dental care in the past year (21.1% vs 8.2%, P = .001),
      brush their teeth less than twice a day (37.1% vs 25.2%, P = .041), or be read to
      less than 3 times per week (31.0% vs 13.7%, P < .001) compared with children of
      mothers without depressive symptoms. In addition, mothers with depressive
      symptoms were more likely to describe inconsistent discipline practices (36.6% vs
      20.1%, P = .005) and less confidence in their parenting (39.4% vs 18.5%, P <
      .001). All associations remained significant in multivariate analyses controlling
      for maternal race, ethnicity, education, income, age, and household structure.
      CONCLUSIONS: Maternal depressive symptoms are associated with diminished positive
      parenting behaviors including dental care, reading, and discipline consistency
      for older preschoolers. These findings have implications for clinical pediatrics
      as well as preventive public health efforts.

PMID- 16443182
TI  - Identified attention-deficit/hyperactivity disorder and medically attended,
      nonfatal injuries: US school-age children, 1997-2002.
AB  - OBJECTIVE: To determine the medically attended, nonfatal injury rate among
      children 6-17 years of age ever and never identified with attention
      deficit/hyperactivity disorder (ADHD). METHODS: An analysis was performed of
      parentally reported injury episodes during the past 3 months and current
      demographic characteristics of 3,741 sample children ever identified with ADHD
      and 48,243 never identified with ADHD in the 1997-2002 National Health Interview
      Surveys. RESULTS: The annualized rate of injury was 204 episodes per 1,000 among
      children with ADHD compared with 115 episodes per 1,000 among children without
      ADHD. Injury episode rates were higher for children with ADHD regardless of age,
      sex, or health insurance. Logistic regression, which controlled for confounding
      risk factors, showed a robust association between ADHD and injury. The adjusted
      odds ratio (OR) for ADHD (OR(adj) = 1.83) was similar to the ORs for other
      important predictors of injury, such as male sex (OR(adj) = 1.45), older age
      (OR(adj) = 1.50), and private health insurance (OR(adj) = 1.44). Children with
      other health conditions had an increased odds for injury (OR(adj) = 1.51 for
      children with other developmental disorders and OR(adj) = 1.53 for children with
      physical disorders). Characteristics of injury episodes were generally similar
      for children with and without ADHD. CONCLUSIONS: Results from a large, nationally
      representative sample indicate that children ever identified with ADHD were more
      likely to have a medically attended, nonfatal injury than children never
      identified with ADHD. The increased odds of injury among children with ADHD could
      not be attributed to other confounding risk factors. Children with ADHD may
      benefit from targeted injury prevention efforts.

PMID- 16443183
TI  - Emergency department use and costs for youth with attention-deficit/hyperactivity
      disorder: associations with stimulant treatment.
AB  - OBJECTIVE: To investigate whether, among youth with attention
      deficit/hyperactivity disorder (ADHD), stimulant treatment is associated with
      reduced emergency department (ED) use and medical costs. METHODS: We previously
      reviewed the complete and detailed school and medical records of all individuals
      born 1976-1982 in Rochester, Minn, to identify those who met criteria for ADHD
      between age 5 years and emigration from the area. Stimulant treatment (all
      start/stop dates, dosages) was also abstracted. This study followed birth cohort
      members with ADHD in provider-linked billing data from January 1, 1987 (billing
      data first available), to age 18 for outcomes: ED visits, ED costs, and medical
      costs. For each outcome, we analyzed associations with 1) any stimulants
      (yes/no), 2) proportion of follow-up time on stimulants, and 3) among those
      treated with stimulants, periods on versus off stimulants. RESULTS: Of 313 youth
      with ADHD, 231 (74%) received any stimulants; treatment duration ranged from 14
      days to 11.8 years. Treated and untreated youth were similar with respect to
      median annual ED visits (0.5 vs 0.5) and medical costs (661 US dollars vs 741 US
      dollars) (P > .05); however, increasing proportion of follow-up on stimulants was
      associated with fewer ED visits (P= .02) and higher medical costs (P< .001). The
      231 treated youth experienced an average of 3.7 periods on and off stimulants;
      while receiving stimulants, they exhibited fewer ED visits (P= .02), lower ED
      costs (P = .03), and higher medical costs (P< .001) compared with periods off
      stimulants. CONCLUSIONS: Among youth with ADHD, extended stimulant treatment is
      associated with decreased ED visits and ED costs, but higher total medical costs.

PMID- 16443185
TI  - Parents' trust in their child's physician: using an adapted Trust in Physician
      Scale.
AB  - OBJECTIVES: To assess the performance of the Pediatric Trust in Physician Scale
      (Pedi-TiPS) that refers to a child's physician and is a modified version of the
      Trust in Physician Scale (TiPS), and to explore the association of trust to
      demographic variables. METHODS: We performed a cross-sectional survey of parents
      in pediatric specialty and primary care sites. Parents completed an anonymous
      questionnaire that included the Pedi-TiPS. Our main outcome variable was total
      Pedi-TiPS score (higher scores = higher trust). Reliability was determined by
      Cronbach's alpha. Bivariate comparisons and linear regression modeling explored
      potential associations between demographic variables and total score. RESULTS:
      Five hundred twenty-six parents completed surveys (73% response rate). The mean
      total score was 45.4 (SD 6), with good internal consistency (alpha = .84). In
      bivariate analysis, lower scores were associated with being a father (P = 0.03),
      older parent age (P = 0.02), private insurance status (P < 0.01), parent
      education greater than high school (P = 0.04), and not having a child age <3
      years (P = 0.03). In a regression model adjusted for other factors, parents who
      were either African American (P = 0.05), or "other" race (P < 0.01), parents with
      private insurance (P = 0.02), and parents who had no children <3 years of age (P
      = 0.04) had lower trust. CONCLUSIONS: The Pedi-TiPS has properties similar to the
      original instrument. We found associations between trust and demographic factors
      that should be confirmed with further studies.

PMID- 16443184
TI  - A walk in the patients' shoes: a step toward competency development in systems
      based practice.
AB  - OBJECTIVES: To implement and evaluate the effectiveness of scenario-based
      learning as a method for teaching systems-based practice to pediatric residents.
      METHODS: Twelve pediatric residents at the University of Florida/Jacksonville
      participated in an active learning scenario experience during their 1-month
      community pediatrics block rotation from January 2003 to April 2004. A scenario,
      developed in partnership with community-based organizations, required the
      residents to assume the role of a parent faced with multiproblem life situations
      requiring skills in prioritizing problems and identifying and accessing community
      resources to address them. Residents documented their assessment of the
      experience as they went through it by making entries into a learning portfolio
      and at the end of the experience through written evaluations and exit interviews.
      A case study design was used to assess resident-perceived impact of this
      experience. Qualitative methods were used to analyze data from resident portfolio
      entries, resident written evaluation surveys, and resident exit interviews.
      RESULTS: Five themes, some of which reflect competencies in systems-based
      practice, emerged from the data: development of empathy and compassion, increased
      understanding of the barriers facing patients and families, increased
      appreciation of social determinants of health, self-perceived increased ability
      to serve patients, and advantages of active learning. CONCLUSIONS: Active
      learning experiences that simulate patient situations can be incorporated into
      community pediatrics training for residents, increasing perceived competence in
      systems-based practice.

PMID- 16443186
TI  - Asymmetric relationship between driving and safety skills.
AB  - We hypothesized that the combination of self reported high ratings of driving
      skills and low ratings of safety skills creates a serious risk for road accident
      involvement. This study was aimed at investigating the asymmetric interplay
      between driving and safety skills among Turkish drivers (N=785) using the Driving
      Skills Inventory [Lajunen, T., Summala, H., 1995. Driver experience, personality,
      and skill and safety motive dimensions in drivers' self-assessments. Pers. Indiv.
      Differ. 19, 307-318]. The assumed asymmetric interactions were tested on a number
      of outcome variables representing risky driving using moderated regression
      analyses. The results revealed that driving skills moderated the effects of
      safety skills on six out of the eight outcome variables including the number of
      accidents, tickets, overtaking tendencies, speed on motorways, and aggressive
      driving style. Results suggested that high levels of safety skills buffer the
      negative effect of overconfidence resulting from exaggerated ratings of self
      reported driving skills.

PMID- 16443187
TI  - [The development of operating tables].
AB  - Operating tables evolved in several stages. The most dynamic period was situated
      between 1860 and 1920: the surgeons of numerous countries were conscious of the
      necessity of specific tables for surgery. Introduction of anaesthesia in 1846 and
      asepsis in 1870 have strongly allowed this development.

PMID- 16443188
TI  - [Rupture of hepatic focal nodular hyperplasia. About two cases].
AB  - The diagnostics of focal nodular hyperplasia is reached through the use of
      imaging. When the diagnostic is certain, surgical abstention is the rule.
      Nevertheless, we were confronted with two cases of a rare complication; that of
      intraperitoneal rupture. In this situation, we suggest to first do an
      arteriography to control the bleeding, then to perform surgery when the patient
      has reached hemodynamic stability. Spontaneous rupture as a complication of
      benign nodular hyperplasia remains a rare event and only five cases were reported
      in litterature.

PMID- 16443189
TI  - [Survival and prognostic factors of colorectal adenocarcinoma: analytic
      multifactor review of 150 cases].
AB  - INTRODUCTION: Prognostic factors have a pivotal role in clinical oncology. They
      are helpful in the selection of treatment; provide insights into the disease
      process and the therapic response. The number of possibility useful prognosis
      factors in the colorectal cancer is large. This study attempts to observe the
      survival of colorectal adenocarcinoma and to find prognostic factors and other
      variables potentially associated with outcome of colorectal adenocarcinoma.
      MATERIAL AND METHODS: It's a retrospective study based on 150 patients with
      colorectal adenocarcinoma from 1990 to 2002. There were 150 patients aged of 58
      years (median 61 years) with 1.4 sex-ratio. 84 patients had colon adenocarcinoma
      and 66 patients had rectal adenocarcinoma. In histological exam the
      adenocarcinoma was well differenced in 69 cases (46%), and undifferentiated in 17
      cases (18, 3%). RESULTS: Locoregional extension was found in 18 cases and
      metastatic extension in 45 cases with hepatic metastasis in 37 cases and
      pulmonary metastasis in 8 cases. There were 6 cases of peritoneal localized
      carcinosis and 6 cases of ovary metastasis. There were 6 patients (4%) Dukes
      stage I TNM, 61 stage II (40, 7%), 51 stage III TNM (34%) and 32 patients stage
      IV TNM (34%). All patients had surgical curative resection associated with
      adjuvant chemotherapy in 60 cases of colon adenocarcinoma and preoperative
      radiotherapy in 33 cases of rectal adenocarcinoma. After a follow up of 46
      months, 52 patients was died (10 operative mortality), 35 patients were lost of
      view and 63 patients were still alive at the point date. Median survival was 20
      months with 95% confidence interval: (4, 2-7, 8). Overall one year and 5 years
      survival were respectively 92,8% and 26,3%. Various prognostic factors had been
      identified through univariate (Kaplan-Meier) then multivariate (Cox) analyze. In
      addition to the clinical factors, we found of significant prognostic value
      undifferentiated adenocarcinoma and an elevated value of serum carcinoembryonic
      antigen>5 ng/ml.

PMID- 16443190
TI  - Effect of vascular endothelial growth factor on RANK gene expression in
      osteoclast precursors and on osteoclastogenesis.
AB  - OBJECTIVE: The aim of this study was to determine if vascular endothelial growth
      factor (VEGF) can upregulate the gene expression of receptor activator of nuclear
      factor kappa B (RANK) in osteoclast precursors, as does CSF-1. A secondary aim
      was to determine if VEGF can promote osteoclastogenesis in vitro comparable to
      CSF-1. DESIGN: Osteoclast precursors (mononuclear cells) were incubated with
      different concentrations of VEGF, CSF-1, or a combination of the two, and the
      gene expression of RANK was determined by RT-PCR. A TRAP assay also was conducted
      to determine their effect on osteoclastogenesis. An Alamar blue assay was done to
      analyse the effect of the molecules on proliferation of the osteoclast
      precursors. RESULTS: VEGF upregulated RANK expression in osteoclast precursors as
      effectively as CSF-1. VEGF did not promote osteoclastogenesis, as did CSF-1. A
      combination of the two did. CSF-1 enhanced proliferation of the osteoclast
      precursors but VEGF did not. However, VEGF in combination with CSF-1 did increase
      proliferation. CONCLUSIONS: At the time of the secondary burst of
      osteoclastogenesis prior to tooth eruption, VEGF expression in the dental
      follicle is high but the expression of CSF-1 is low. This study demonstrates that
      VEGF can fully substitute for CSF-1 to upregulate the RANK expression in
      osteoclast precursors that is needed for osteoclastogenesis. However, VEGF alone
      neither can promote osteoclastogenesis nor stimulate proliferation of the
      osteoclast precursors in vitro. For proliferation and osteoclastogenesis, a low
      dose of CSF-1 in combination with VEGF is needed.

PMID- 16443192
TI  - Structure-based drug design meets the ribosome.
AB  - The high-resolution structures of the bacterial ribosomal subunits and those of
      their complexes with antibiotics have advanced significantly our understanding of
      small-molecule interactions with RNA. The wealth of RNA structural data generated
      by these structures has allowed computational chemists to employ a drug discovery
      paradigm focused on RNA-based targets. The structures also show how target-based
      resistance affects antibiotics acting at the level of the ribosome. Not only are
      the sites pinpointed where different classes of antibiotics inhibit protein
      synthesis, but their orientations, relative dispositions, and unique mechanisms
      of action are also revealed at the atomic level. Both the 30S and the 50S
      ribosomal subunits have been shown to be "targets of targets", offering several
      adjacent, functionally relevant binding pockets for antibiotics. It is the
      detailed knowledge of these validated locations, or ribofunctional loci, plus the
      mapping of the resistance hot-spots that allow the rational design of next
      generation antibacterials. When the structural information is combined with a
      data-driven computational toolkit able to describe and predict molecular
      properties appropriate for bacterial cell penetration and drug-likeness, a
      structure-based drug design approach for novel antibacterials shows great
      promise.

PMID- 16443191
TI  - Riboflavin enhances the assembly of mitochondrial cytochrome c oxidase in C.
      elegans NADH-ubiquinone oxidoreductase mutants.
AB  - Mitochondrial respiratory chain dysfunction is responsible for a large variety of
      early and late-onset diseases. NADH-ubiquinone oxidoreductase (complex I) defects
      constitute the most commonly observed mitochondrial disorders. We have generated
      Caenorhabditis elegans strains with mutations in the 51 kDa active site subunit
      of complex I. These strains exhibit decreased NADH-dependent respiration and
      lactic acidosis, hallmark features of complex I deficiency. Surprisingly, the
      mutants display a significant decrease in the amount and activity of cytochrome c
      oxidase (complex IV). The metabolic and reproductive fitness of the mutants is
      markedly improved by riboflavin. In this study, we have examined how the assembly
      and activity of complexes I and IV are affected by riboflavin. Our results reveal
      that the mutations result in variable steady-state levels of different complex I
      subunits and in a significant reduction in the amount of COXI subunit. Using
      native gel electrophoresis, we detected assembly intermediates for both complexes
      I and IV. Riboflavin promotes the assembly of both complexes, resulting in
      increased catalytic activities. We propose that one primary pathogenic mechanism
      of some complex I mutations is to destabilize complex IV. Enhancing complex I
      assembly with riboflavin results in the added benefit of partially reversing the
      complex IV deficit.

PMID- 16443193
TI  - Ceramide-1-phosphate activates cytosolic phospholipase A2alpha directly and by
      PKC pathway.
AB  - Ceramide-1-phosphate (C1P), a novel bioactive sphingolipid, is implicated in the
      vital cellular processes such as cell proliferation and inflammation. The role of
      C1P on activity of cytosolic phospholipase A2alpha (cPLA2alpha), a key enzyme for
      the release of arachidonic acid (AA) and prostanoids, has not been well
      elucidated. In this study, we investigated the effect of C1P on the release of AA
      from L929 cells and a variant, which lacks cPLA2alpha expression, C12 cells. C1P
      at 30 microM alone induced AA release from L929 cells without an increase in
      intracellular Ca2+ concentration. C1P-induced AA release was marginal in C12
      cells, and treatment with an intracellular Ca2+ chelator (BAPTA-AM) or an
      inhibitor of cPLA2alpha (2 microM pyrrophenone) decreased C1P-induced AA release
      in L929 cells. C1P increased the enzymatic activity of cPLA2alpha over two-fold
      in the presence of Ca2+. C1P triggered the translocation of cPLA2alpha and its C2
      domain from the cytosol to the perinuclear region in CHO-K1 cells. Interestingly,
      C1P at 10 microM synergistically enhanced ionomycin-induced AA release from L929
      cells. The AA release induced by C1P with and without ionomycin decreased by
      treatment with protein kinase C (PKC) inhibitor (10 microM GF109203X) and in the
      PKC-depleted cells. C1P at 10 microM stimulated the translocation of PKC (alpha
      and delta) from the soluble to the membrane fractions. We propose that C1P
      stimulates AA release via two mechanisms; direct activation of cPLA2alpha, and
      the PKC-dependent pathway.

PMID- 16443194
TI  - Transhemispheric depolarizations persist in the intracerebral hemorrhage swine
      brain following corpus callosal transection.
AB  - Spontaneous episodes of spreading depression (SD) originating in multiple sources
      adjacent to a focal intracerebral hemorrhage (ICH) propagate into brain regions
      away from the lesion site soon after injury onset. Although these transient
      depolarizations have not been established in the opposite hemisphere of the swine
      ICH model, we have reported a diminishing of sensory responsiveness in this
      homotopic brain region following induction of a unilateral hemorrhage lesion.
      This study examined whether transient depolarizations exist in this distant brain
      region contralateral to the ICH site. Electrocorticographic (ECoG) recordings of
      brain activity were collected bilaterally from the primary somatosensory (SI)
      cortices of the swine brain prior to and immediately after an intracerebral
      injection of collagenase or saline or the insertion of the infusion pipette into
      the SI cortex of the right hemisphere. Transient depolarizations were present in
      both hemispheres of all the experimental groups. The earliest negative DC
      potential shifts were observed in the injured SI cortex within the first hour
      after collagenase injection, as compared to T = 3 h in the saline-injected group
      and T = 4 h in the infusion pipette only group. In contrast, transient
      depolarizations were first detected in the left SI cortex contralateral to the
      lesioned hemisphere within 2 h after collagenase infusion, by T = 4 h after
      saline infusion and by T = 3 h in the pipette only group. Propagating waves of
      negative DC potential shifts continued in both brain hemispheres, particularly in
      the ICH group, throughout the 11-h recording period. This novel finding of
      recurrent depolarizing waves in the hemisphere contralateral to the injury site
      prompted us to examine whether corpus callosal connections may play a role in
      this transhemispheric phenomenon. In a separate group of animals, the corpus
      callosum was transected prior to acquiring DC potential recordings and
      collagenase injection. The onset pattern of negative DC shifts in the
      callosotomized + collagenase-injected group was similar to the collagenase group
      with an intact corpus callosum. Initial generation of SD in the callosotomized +
      collagenase-injected group occurred by T = 1 h in the ICH injured right
      hemisphere and T = 2 h in the contralateral hemisphere. These transient
      depolarizations also persisted throughout 11-h recording period indicating that
      the corpus callosal transection did not hinder these remote propagating waves of
      depolarization. The presence of SD in the SI cortices of both hemispheres in all
      experimental groups of this study suggests that a focal mechanical or hemorrhagic
      injury increases the susceptibility of distant ipsilateral and contralateral
      brain regions to depolarizing perturbations. The mechanism for these transient
      depolarizations in the contralateral hemisphere apparently does not involve
      transhemispheric propagation along corpus callosal fibers.

PMID- 16443195
TI  - Expression of sex-steroid receptors and steroidogenic enzymes in the carotid body
      of adult and newborn male rats.
AB  - This study describes the localization and pattern of expression of estradiol and
      progesterone receptors as well as key enzymes for steroid synthesis (i.e. P450
      side-chain-cleavage--P450scc, and P450 aromatase--P450Aro) in the carotid body
      (CB) and superior cervical ganglion (SCG) of adult, newborn and late fetal male
      rats, using immunohistochemistry, Western blot and real-time RT-PCR. Our results
      show a constitutive expression of the beta estradiol receptor (Erbeta) and the 80
      kDa and 60 kDa progesterone receptors (PR-A and PR-C) isoforms in the CB, while
      in the SCG Eralpha, Erbeta, PR-A and PR-C are expressed. While P450Aro staining
      was negative, P450scc staining was strong both in the SCG and CB. In late fetal
      and newborn rats, Eralpha was not detected in the CB or SCG, but a slight
      staining appeared for P450 aromatase in the CB, and to a lesser extent in SCG.
      P450scc was strongly expressed in CB and SCG of late fetal and newborn rats. We
      conclude that the carotid body shows a constitutive expression of Erbeta and PR
      and may be able to synthesize steroids, including estradiol during late fetal
      life.

PMID- 16443197
TI  - Localization of Id2 mRNA in the adult mouse brain.
AB  - Id proteins are negative regulators of basic helix-loop-helix transcription
      factors and are involved in cellular differentiation and proliferation. Four
      members of the Id gene family exhibit closely related but distinct expression
      patterns in various mammalian organs of not only embryos but also adults. Among
      them, Id2 is known to be expressed in Purkinje cells and neurons in the cortical
      layers of the adult mouse brain, suggesting that Id2 is involved in some neural
      functions in the adult. To get insight into the role of Id2 in the nervous
      system, we investigated the localization of Id2 mRNA-expressing cells in the
      adult mouse brain in detail by in situ hybridization with the radiolabeled
      antisense probe and compared it with the localization of other Id gene family
      members. The results indicated that Id2 mRNA is detected in more varied brain
      regions than previously reported. These regions include the amygdaloid complex,
      caudate putamen, globus pallidus, substantia nigra pars reticulata,
      suprachiasmatic nucleus, and the anterior part of the subventricular zone. These
      results suggest the possibility that Id2 plays a role in the neural activity and
      cognitive functions. On the other hand, Id1 was barely detectable. Although
      moderate or low expression of Id3 was observed diffusely, high expression was
      observed in some specific regions including the molecular layer of the dentate
      gyrus and the external capsule. Id4 mRNA was detected in the regions such as the
      caudate putamen and the lateral amygdaloid nucleus. Thus, the expression pattern
      of Id2 is distinct from those of other Id gene family members.

PMID- 16443196
TI  - Differential distribution of ELMO1 and ELMO2 mRNAs in the developing mouse brain.
AB  - ELMO is an upstream regulator of the Rho family small GTPase Rac. We investigated
      the distributions of mRNAs of two subtypes of ELMO, ELMO1 and ELMO2, in the
      developing mouse brain. Both ELMO1 and ELMO2 mRNAs are widely distributed in the
      developing mouse brain, but they were expressed in different neuronal populations
      in the cerebral cortex, thalamus, and cerebellum. Thus, ELMO1 and ELMO2 may play
      different roles during brain development.

PMID- 16443198
TI  - Brain mechanism of Stroop interference effect in Chinese characters.
AB  - Event-related brain potentials were measured when 11 healthy Chinese subjects
      finished Chinese Characters Stroop tasks. The behavioral data showed that the
      Stroop task yielded a robust Stroop interference effect as indexed by longer RT
      for incongruent than congruent color words. Scalp ERP analysis revealed the
      neurophysiological substrate of the interference effect: a greater negativity in
      the incongruent as compared to the congruent was found between 350 and 550 ms
      poststimulus over midline fronto-central scalp regions. Dipole source analysis
      (BESA software) of the difference wave (incongruent-congruent) indicated that a
      generator localized in prefrontal cortex (PFC) contributed to this effect,
      possibly related to conflict processing and response selection. The results
      provided electrophysiologic evidences of the brain and cognitive mechanism of
      Stroop interference effect in Chinese characters and suggested that the
      difference between Chinese characters and English words had influence on temporal
      patterns of the Stroop interference effect.

PMID- 16443199
TI  - Neuroprotective effect of atrial natriuretic peptide against NMDA-induced
      neurotoxicity in the rat retina.
AB  - Atrial natriuretic peptide (ANP) can regulate aqueous humor production in the eye
      and has recently been suggested to play some functional roles in the retina. It
      has also been reported that ANP increases tyrosine hydroxylase (TH) mRNA levels
      and intracellular dopamine levels in PC12 cells. The effect of ANP on TH levels
      and the role of ANP in retinal excitotoxicity remain unknown. In this study, we
      investigated the effects of ANP on TH expression and dopamine levels in rat
      retina after intravitreal injection of NMDA. Immunohistochemistry localized
      natriuretic peptide receptor-A (NPRA) in the ganglion cell layer (GCL), the inner
      nuclear layer (INL) and the outer nuclear layer (ONL) in the rat retina.
      Quantitative real-time PCR and Western blot analysis showed a dramatic reduction
      in retinal TH levels 5 days after NMDA injection, while ANP, at a concentration
      of 10(-4) M, ameliorated this reduction in TH mRNA and TH protein levels. High
      performance liquid chromatography (HPLC) analysis showed that NMDA reduced
      dopamine levels in the retina, and that ANP attenuated this reduction. Moreover,
      morphological analysis showed that ANP ameliorated NMDA-induced neurotoxicity
      through NPRA. The ameliorative effect of ANP was inhibited by a dopamine D(1)
      receptor antagonist. These results suggest that ANP may have a neuroprotective
      effect through possible involvement of dopamine induction.

PMID- 16443200
TI  - The selective A2A receptor antagonist SCH 58261 protects from neurological
      deficit, brain damage and activation of p38 MAPK in rat focal cerebral ischemia.
AB  - We investigated the protective effect of subchronic treatment of the A2A receptor
      antagonist, SCH 58261 (0.01 mg/kg, i.p.), administered 5 min, 6 h and 15 h after
      permanent right middle cerebral artery occlusion (MCAo). Twenty-four hours after
      ischemia, an extensive pallid area, evaluated by cresyl violet staining, is
      evident in the vascular territories supplied by the MCA, the striatum and the
      sensory motor cortex. The pallid area reflects the extent of necrotic neurons.
      Soon after waking, rats showed a definite contralateral turning behavior which
      was significantly reduced by SCH 58261 treatment. Twenty-four hours after MCAo,
      SCH 58261 significantly improved the neurological deficit and reduced ischemic
      damage in the striatum and cortex. Phospho-p38 mitogen-activated protein kinase
      (MAPK), evaluated by Western Blot, increased by 500% in the ischemic striatum 24
      h after MCAo. SCH 58261 treatment significantly reduced phospho-p38 MAPK by 70%.
      Microglia was immunostained using the OX-42 antibody. Phospho-p38 MAPK and OX-42
      immunoreactive cells are localized in the ventral striatum and frontoparietal
      cortex. Furthermore, both OX-42 and phospho-p38 MAPK-immunoreactive cells have
      overlapping morphological features, typical of reactive microglia. SCH 58261
      reduced phospho-p38 MAPK immunoreactivity in the striatum and in the cortex
      without changing the microglial cell morphology. These results indicate that the
      protective effect of the adenosine antagonist SCH 58261 during ischemia is not
      due to reduced microglial activation but involves inhibition of phospho-p38 MAPK
      and suggest that treatment with the A2A antagonist from the first hour to several
      hours after ischemia may be a useful therapeutic approach in cerebral ischemia.

PMID- 16443201
TI  - Genetic analysis of the cystatin C gene in familial and sporadic ALS patients.
AB  - Bunina bodies, small eosinophilic intraneuronal inclusions, stain positive for
      cystatin C and are the only specific pathological hallmark of amyotrophic lateral
      sclerosis (ALS). We screened the cystatin C gene (CST3) for mutations in 57
      sporadic ALS patients and 12 familial ALS cases that did not possess a SOD1
      mutation. We detected the known polymorphism in exon 1, a G/A transition at +73,
      in both familial and sporadic ALS patients. However, the allelic and genotypic
      frequencies of the +73 G/A polymorphism did not differ between ALS patients and
      control samples. No other mutation was detected in the ALS patients. The results
      reported here indicate that there may not be a direct genetic link between
      cystatin C and ALS, and it may be that deficits occur in proteins that interact
      with cystatin C.

PMID- 16443202
TI  - New variability in cerebrovascular anatomy determines severity of hippocampal
      injury following forebrain ischemia in the Mongolian gerbil.
AB  - Transient bilateral carotid artery occlusion in the Mongolian gerbil is a widely
      used model of forebrain ischemia due to species-specific absence of communicating
      arteries between the middle and posterior cerebral arteries. We have found that
      transient carotid occlusion induces a wide variation in histological injury of
      the hippocampus, suggesting that Mongolian gerbils currently available in the US
      have anomalous connections between the vertebral and carotid circulations. We
      subjected Mongolian gerbils from Harlan Sprague-Dawley and Charles River
      Laboratories to 5 min of bilateral carotid occlusion under continuous striatal
      temperature control and assessed hippocampal injury histologically 5 or 14 days
      later. The severity of occlusion-induced hippocampal injury depended on the
      presence and size of posterior cerebral communicating arteries. Injury was
      markedly attenuated in hippocampi having ipsilateral communicating arteries >50
      microm in diameter. In contrast, severe ischemic injury occurred when either no
      posterior communicating artery was present, or when communicating arteries were
      smaller than 50 microm in diameter. Ischemic injury was independent of any
      communicating arteries on the contralateral side. Communicating arteries were
      present in 90% of gerbils from each vendor, ranging from 19 microm to 125 microm
      in diameter. The high prevalence of posterior communicating arteries and their
      profound effect on attenuating hippocampal injury indicates that an understanding
      of the presence and size of posterior communicating cerebral arteries in each
      animal is now required to interpret the extent of hippocampal injury following
      bilateral carotid artery occlusion in this species.

PMID- 16443203
TI  - Effect of allopurinol on brain adenosine levels during hypoxia in newborn
      piglets.
AB  - Adenosine, a purine nucleoside, is a potent inhibitory neuromodulator in the
      brain which may provide an important endogenous neuroprotective role during
      hypoxia-ischemia. Allopurinol, a xanthine oxidase inhibitor, blocks purine
      degradation and may result in the accumulation of purine metabolites, including
      adenosine, during hypoxia. The present study determines the effect of allopurinol
      administration prior to hypoxia on brain levels of adenosine and purine
      metabolites in the newborn piglet. Twenty-two newborn piglets (age 3-7 days) were
      studied: 5 untreated normoxic and 6 allopurinol-treated normoxic controls were
      compared to 5 untreated hypoxic and 6 allopurinol-treated hypoxic animals. Brain
      tissue energy metabolism was continuously monitored during hypoxia by (31)P NMR
      spectroscopy. Brain tissue levels of purines increased in both hypoxic groups
      during hypoxia, however, there were significantly higher increases in brain
      tissue levels of adenosine (66.5 +/- 30.5 vs. 19.4 +/- 10.7 nmol/gm), P < 0.01
      and inosine (265 +/- 97.6 vs. 162.8 +/- 38.3 nmol/gm), P = 0.05 in the
      allopurinol-treated hypoxic group. Allopurinol inhibits purine degradation under
      severe hypoxic conditions and results in a significant increase in brain tissue
      levels of adenosine and inosine. The increased accumulation of CNS adenosine
      during hypoxia which is seen in the allopurinol-treated animals may potentiate
      adenosine's intrinsic neuroprotective mechanisms.

PMID- 16443205
TI  - Comparison of the in vitro efficacy of mu, delta, kappa and ORL1 receptor
      agonists and non-selective opioid agonists in dog brain membranes.
AB  - Morphine and related opioid agonists are frequently used in dogs for their
      analgesic properties, their sedative effects and as adjuncts to anesthesia. Such
      compounds may be effective through a combined action at mu-, delta- and kappa
      opioid receptors. In this work, the in vitro relative agonist efficacy of ligands
      selective for mu (DAMGO)-, delta (SNC80)- and kappa (U69593)-opioid receptors as
      well as the opioid receptor-like receptor ORL(1) (orphaninFQ/nociceptin) which
      may mediate nociceptive or antinociceptive actions was determined using the
      [35S]GTPgammaS binding assay in membrane homogenates from the frontal cortex,
      thalamus and spinal cord of beagle dogs. In addition, other analgesics commonly
      used in the dog were investigated. For the receptor-selective compounds, maximum
      stimulation of [35S]GTPgammaS binding decreased in the order kappa > ORL1 > delta
      > mu in cortical homogenates, compared with mu > ORL1 > kappa > delta in thalamic
      and spinal cord homogenates. For other opioids examined, efficacy decreased in
      the order etorphine >> morphine > fentanyl = oxymorphine > butorphanol =
      oxycodone = nalbuphine. There was no significant difference in the potency of
      compounds to stimulate [35S]GTPgammaS binding between cortex and thalamus, with
      the exception of etorphine. Buprenorphine, the partial mu-opioid receptor agonist
      and kappa-, delta-opioid receptor antagonist, which does have analgesic efficacy
      in the dog, showed no agonism in any tissue but was an effective mu-opioid
      receptor > ORL1 receptor antagonist. The results show that the ability of
      agonists to stimulate [35S]GTPgammaS binding relates to the receptor distribution
      of opioid and ORL1 receptors in the dog.

PMID- 16443204
TI  - Intuitive interference in quantitative reasoning.
AB  - It is well known that surface features of a task can queue multiple reasoning
      strategies. Interference or conflict among the strategies is signaled by
      increasing reaction times and error rates. To determine the neural basis of this
      interference, we studied 14 volunteers using event-related fMRI, as they compared
      the perimeters of geometrical shapes in congruent (where the shapes' perimeter
      changed in the same direction as its area) and incongruent (where the shapes'
      perimeter was conserved but its area changed) conditions. We found evidence for
      the engagement of bilateral parietal lobe systems during congruent trials and
      incorrect incongruent trials. Activation of bilateral orbital frontal cortex was
      evident when subjects inhibited interference associated with processing the
      salient feature 'area' and correctly completed the perimeters in the incongruent
      condition. Varying the level of interference exerted by the unattended feature
      'area' (filled vs. unfilled shapes) affected the relative level of activation of
      right parietal regions but not orbital frontal cortex suggesting that the former
      is responding to the degree of facilitation while the latter is responsive to the
      presence of conflict (rather than the degree of conflict).

PMID- 16443206
TI  - Neural correlates of spatial frequency processing: A neuropsychological approach.
AB  - We examined the neural correlates of spatial frequency (SF) processing through a
      gender and neuropsychological approach, using a recognition task of filtered
      (either in low spatial frequencies/LSF or high spatial frequencies/HSF) natural
      scene images. Experiment 1 provides evidence for hemispheric specialization in SF
      processing in men (the right hemisphere is predominantly involved in LSF analysis
      and the left in HSF analysis) but not in women. Experiment 2 aims to investigate
      the role of the right occipito-temporal cortex in LSF processing with a
      neurological female patient who had a focal lesion of this region due to an
      embolization of an arterioveinous malformation. This study was conducted 1 week
      before and 6 months after the surgical intervention. As expected, after the
      embolization, LSF scene recognition was more impaired than HSF scene recognition.
      These data support the hypothesis that the right occipito-temporal cortex might
      be preferentially specialized for LSF information processing and more generally
      suggest a hemispheric specialization in SF processing in females, although it is
      difficult to demonstrate in healthy women.

PMID- 16443208
TI  - The role of peroxynitrite in chemical preconditioning with 3-nitropropionic acid
      in rat hearts.
AB  - OBJECTIVES: 3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate
      dehydrogenase, has been shown to protect against ischemic injury in the brain and
      in the heart via a preconditioning-like effect; however, the cellular mechanism
      is not known. The aim of the present study was to investigate if 3-NP
      pretreatment reduces infarct size and if altered metabolism of nitric oxide and
      reactive oxygen species are involved. METHODS: Hearts were assigned into 3
      groups: 3 intermittent cycles of 5 min no-flow ischemia separated by 5 min
      aerobic perfusion protocol were used to induce ischemic preconditioning as a
      positive control; a time-matched non-preconditioning group served as control; and
      3-NP (20 mg/kg, i.p.) was injected 3 h before the perfusion protocol to induce
      pharmacological preconditioning. Hearts from all groups were then subjected to 30
      min global ischemia followed by 120 min reperfusion. RESULTS: Infarct size and
      lactate dehydrogenase release were significantly reduced after
      ischemia/reperfusion. While cardiac nitric oxide (NO) was increased, superoxide
      formation, nitrotyrosine level, and cardiac NADH oxidase and xanthine oxidase
      (XO) activities were markedly reduced by 3-NP administration. Cardiac activities
      of NO synthase and superoxide dismutase were not changed by 3-NP. CONCLUSION:
      This is the first demonstration in the rat myocardium that 3-NP induces
      pharmacological preconditioning, thereby limiting infarct size, and that this
      effect is associated with increased NO bioavailability and reduced peroxynitrite
      formation due to inhibition of superoxide formation by XO and NADH oxidase.

PMID- 16443207
TI  - Infarct-sparing effect of myocardial postconditioning is dependent on protein
      kinase C signalling.
AB  - OBJECTIVE: Using non-selective and selective protein kinase C (PKC) epsilon and
      delta isoform inhibitors, we tested the hypothesis that the cardioprotective
      phenotype invoked by postconditioning (postcon) is dependent on PKC signalling.
      Furthermore, we determined whether postconditioning alters pPKCepsilon and/or
      pPKCdelta in cytosolic and mitochondrial fractions. METHODS: Male Sprague-Dawley
      rats underwent 30 min left coronary artery (LCA) occlusion followed by 3 h of
      reperfusion. Rats were randomised to the following groups: Untreated, no
      intervention either before or after LCA occlusion; Postcon, 3 cycles of 10-s full
      reperfusion and 10-s re-occlusion, initiated immediately at the onset of
      reperfusion; Chelerythrine (non-selective PKC inhibitor, 5 mg/kg)+/-postcon;
      Rottlerin (PKCdelta inhibitor, 0.3 mg/kg)+/-postcon; KIE1-1 (PKCepsilon
      inhibitor, 3.8 mg/kg)+/-postcon. A subset of rats was employed to assess
      pPKCepsilon and/or pPKCdelta in sham, Isch/RP (30-min LCA occlusion followed by
      30-min reperfusion), and postcon-treated hearts. RESULTS: Infarct size, expressed
      as area of necrosis as a percentage of the area at risk, AN/AAR (%), was
      significantly reduced by postcon compared to control (untreated) rats (39+/-2%
      vs. 53+/-1% in control, P<0.001). Treatment with chelerythrine alone or the
      PKCepsilon antagonist KIE1-1 alone at reperfusion had no effect on infarct size
      compared to control. In contrast, the infarct-sparing effect of postcon was
      abrogated by non-selective PKC inhibition and PKCepsilon antagonism (50+/-2% and
      50+/-1%, respectively, P<0.002). Inhibition of PKCdelta reduced infarct size to
      values comparable to that in postcon group (36+/-3% vs. 39+/-2%). However,
      postcon in the presence of PKCdelta inhibitor did not enhance the infarct-sparing
      effects (38+/-2%). In addition, pPKCepsilon in postcon hearts was significantly
      higher in the total cell homogenate (10338+/-1627 vs. 4165+/-608 in Isch/RP,
      arbitrary units), and pPKCdelta translocation to mitochondria was significantly
      less (>2-fold decrease) compared to Isch/RP. CONCLUSION: These data suggest that
      postcon modulates PKC during early reperfusion by increasing PKCepsilon
      expression and translocation to a site other than the outer mitochondrial
      membrane, and limits translocation of PKCdelta to mitochondria and associated
      deleterious signalling.

PMID- 16443209
TI  - Heparin interference in whole blood sodium measurements in a pediatric setting.
AB  - OBJECTIVES: In a pediatric setting, the incomplete filling of heparinized
      syringes is not an uncommon occurrence and has led to reports of falsely low
      hyponatremia in our institution. Little is known about heparin interference on
      sodium determination in whole blood, and our study aimed to investigate this
      interference due to excessive concentrations of heparin in pediatric specimens.
      DESIGN AND METHODS: Three different types of syringes were filled with various
      amounts of blood to mimic greater than normal concentrations of heparin.
      Specimens were analyzed on an ABL 725 blood gas analyzer, and corresponding
      plasma fractions were analyzed on a VITROS 950 chemistry system. In a separate
      study, paired patient samples consisting of a capillary tube and microtainer clot
      were similarly analyzed. RESULTS: The presence of lithium heparin at 100 units/mL
      in blood caused a significant negative bias of 2-3 mmol/L in sodium concentration
      with the ABL 725, but no significant bias occurred when the corresponding plasma
      fraction was analyzed on the VITROS 950. For syringes containing electrolyte
      balanced heparin, a similar negative bias was observed for blood but was not
      significant. Capillary tubes contained high concentrations of heparin (>100
      units/mL) even when completely filled. Sodium results from capillary samples
      averaged 3.4 mmol/L lower than the corresponding serum values. These effects were
      independent of the sodium concentration across a wide range. CONCLUSIONS: Small
      blood volumes collected with heparinized sampling devices in pediatric samples
      lead to excess heparin that may significantly affect sodium determinations and
      spur false reports of critical hyponatremia.

PMID- 16443210
TI  - AMPK regulation of mouse oocyte meiotic resumption in vitro.
AB  - We have previously shown that the adenosine analog 5-aminoimidazole-4-carboxamide
      1-beta-d-ribofuranoside (AICAR), an activator of AMP-activated protein kinase
      (AMPK), stimulates an increase in AMPK activity and induces meiotic resumption in
      mouse oocytes [Downs, S.M., Hudson, E.R., Hardie, D.G., 2002. A potential role
      for AMP-activated protein kinase in meiotic induction in mouse oocytes. Dev.
      Biol, 245, 200-212]. The present study was carried out to better define a
      causative role for AMPK in oocyte meiotic maturation. When microinjected with a
      constitutively active AMPK, about 20% of mouse oocytes maintained in meiotic
      arrest with dibutyryl cAMP (dbcAMP) were stimulated to undergo germinal vesicle
      breakdown (GVB), while there was no effect of catalytically dead kinase. Western
      blot analysis revealed that germinal vesicle (GV)-stage oocytes cultured in
      dbcAMP-containing medium plus AICAR possessed elevated levels of active AMPK, and
      this was confirmed by AMPK assays using a peptide substrate of AMPK to directly
      measure AMPK activity. AICAR-induced meiotic resumption and AMPK activation were
      blocked by compound C or adenine 9-beta-d-arabinofuranoside (araA, a precursor of
      araATP), both inhibitors of AMPK. Compound C failed to suppress adenosine uptake
      and phosphorylation, indicating that it did not block AICAR action by preventing
      its metabolism to the AMP analog, ZMP. 2'-deoxycoformycin (DCF), a potent
      adenosine deaminase inhibitor, reversed the inhibitory effect of adenosine on
      oocyte maturation by modulating intracellular AMP levels and activating AMPK.
      Rosiglitazone, an anti-diabetic agent, stimulated AMPK activation in oocytes and
      triggered meiotic resumption. In spontaneously maturing oocytes, GVB was preceded
      by AMPK activation and blocked by compound C. Collectively, these results support
      the proposition that active AMPK within mouse oocytes provides a potent meiosis
      inducing signal in vitro.

PMID- 16443211
TI  - Overgrowth caused by misexpression of a microRNA with dispensable wild-type
      function.
AB  - MicroRNAs (miRNAs) represent an abundant class of non-coding RNAs that negatively
      regulate gene expression, primarily at the post-transcriptional level. miRNA
      genes are frequently located in proximity to fragile chromosomal sites associated
      with cancers and amplification of a miRNA cluster has been correlated with the
      etiology of lymphomas and solid tumors. The oncogenic potential of a miRNA
      polycistron has recently been demonstrated in vivo. Here, we show that
      misexpression of the Drosophila miRNA mirvana/mir-278 in the developing eye
      causes massive overgrowth, in part due to inhibition of apoptosis. A single base
      substitution affecting the mature miRNA blocks the gain-of-function phenotype but
      is not associated with a detectable reduction-of-function phenotype when
      homozygous. This result demonstrates that misexpressed miRNAs may acquire novel
      functions that cause unscheduled proliferation in vivo and thus exemplifies the
      potential of miRNAs to promote tumor formation.

PMID- 16443212
TI  - Effects of mitiglinide and sulfonylureas in isolated canine coronary arteries and
      perfused rat hearts.
AB  - Our aim was to compare the cardiovascular effects of mitiglinide ((+)-monocalcium
      bis[(2S,3a,7a-cis)-alpha-benzylhexahydro-gamma-oxo-2-isoindolinebutyrate]
      dehydrate), a novel hypoglycemic drug, with those of glibenclamide and
      glimepiride, two sulfonylurea drugs. In isolated canine coronary arteries (organ
      bath method), mitiglinide, glibenclamide, and glimepiride competitively
      antagonized the cromakalim-induced relaxation (pA2 values, 5.29, 7.36, and 7.49,
      respectively). In isolated perfused rat hearts (Langendorff method) subjected to
      a 12-min global ischemia followed by a 30-min reperfusion, mitiglinide (3 x 10(
      6) mol/l) altered neither the change in coronary perfusion flow nor the
      alterations in cardiac functions associated with reperfusion. In contrast, both
      glibenclamide (3 x 10(-8) mol/l) and glimepiride (1 x 10(-7) mol/l) significantly
      reduced coronary perfusion flow after reperfusion. Moreover, at 30 min of
      reperfusion: (1) glibenclamide induced a significant increase in left ventricular
      end-diastolic pressure and significant decreases in left ventricular systolic
      pressure, left ventricular developed pressure, and the maximum first derivative
      of left ventricular pressure, while (2) glimepiride induced significant decreases
      in left ventricular developed pressure and the maximum first derivative of left
      ventricular pressure. Thus, the cardiovascular effects of mitiglinide (at least,
      in these rat and dog preparations) may be weaker than those of glibenclamide and
      glimepiride.

PMID- 16443213
TI  - Modulation of iNOS expression by a nitric oxide-releasing derivative of the
      natural antioxidant ferulic acid in activated RAW 264.7 macrophages.
AB  - We have previously reported that NCX 2057, a new chemical entity bearing a nitric
      oxide (NO)-releasing moiety linked to the natural antioxidant ferulic acid, shows
      marked anti-inflammatory properties in a model of chronic brain inflammation. We
      have now studied the effects of NCX 2057 and its metabolic products, ferulic acid
      and NCX 2059, on inducible nitric oxide synthase (iNOS) expression and function
      in lipopolysaccharide/interferon-gamma (LPS/IFNgamma)-stimulated RAW 264.7
      macrophages. NCX 2057 inhibited iNOS mRNA and protein expression (IC(50)=6.2+/
      1.0 microM) without altering iNOS protein degradation rate. NCX 2057 also
      decreased the levels of LPS/IFNgamma-induced nitrite accumulation (IC(50)=4.3+/
      0.7 microM) in RAW 264.7 cells. Conversely, NCX 2059, which does not possess NO
      donating properties, was only weakly effective (IC(50) >100 microM) and ferulic
      acid was inactive. To understand further the mechanisms underlying anti
      inflammatory properties we studied the effects of NCX 2057 on selected
      transcription factors. Unlike ferulic acid, NCX 2057 inhibited LPS-induced
      translocation/activation of the nuclear factor, NF-kappaB, while other
      transcription factors, such as, Sp1, NF-IL2A and STAT-1 were not affected. The
      present data support the concept that NO adds important anti-inflammatory
      properties to ferulic acid. Thus, NCX 2057 represents a new prototype drug for
      the treatment of disorders associated with chronic inflammation and oxidative
      stress.

PMID- 16443214
TI  - Ca2+-activated K+ (KCa) channels are involved in the relaxations elicited by
      sildenafil in penile resistance arteries.
AB  - The aim of the present study was to evaluate the role of K+ channels in the
      vasorelaxant effect of the phosphodiesterase 5 inhibitor, sildenafil, in isolated
      horse penile resistance arteries mounted in microvascular myographs. In
      phenylephrine-precontracted arteries, sildenafil elicited potent relaxations
      which were markedly reduced by raising extracellular K+, by the non-selective
      blocker of Ca2+-activated K+ channels (KCa), tetraethylammonium and by the
      blocker of large- and intermediate-conductance KCa channels, charybdotoxin.
      Sildenafil relaxant responses were also reduced by the selective inhibitor of
      large conductance KCa (BK(Ca)) channels iberiotoxin, but not by the blocker of
      small conductance KCa channels apamin. The inhibitor of the cGMP-dependent
      protein kinase (PKG), Rp-8-Br-PET-cGMPS, reduced the relaxations elicited by
      sildenafil but combined treatment with iberiotoxin and Rp-8-Br-PET-cGMPS did not
      further inhibit these relaxations, compared to the effect of either blocker
      alone. Iberiotoxin also shifted to the right the relaxations elicited by both the
      NO donor, S-nitrosoacetyl-D,L-penicillamine (SNAP) and the adenylate cyclase
      activator forskolin; treatment with both iberiotoxin and Rp-8-Br-PET-cGMPS did
      cause an additional inhibition. The present results demonstrate that the relaxant
      effect of sildenafil and NO in penile resistance arteries is due in part to
      activation of BK(Ca) channels through a PKG-dependent mechanism.

PMID- 16443215
TI  - Dihydrocucurbitacin B, isolated from Cayaponia tayuya, reduces damage in adjuvant
      induced arthritis.
AB  - 23,24-Dihydrocucurbitacin B, from the anti-rheumatic plant Cayaponia tayuya, was
      tested on arthritis induced by adjuvant to corroborate the anti-inflammatory
      properties of this plant. Arthritis was induced in Lewis rats; the resulting
      arthritic rats were then treated with dihydrocucurbitacin B (1 mg/kg orally,
      daily, 1 week). The effect of dihydrocucurbitacin B on the synthesis, release,
      and activity of pro-inflammatory enzymes (elastase, cyclooxygenase-2, and nitric
      oxide synthase-2) as well as its effect on different mediators (tumor necrosis
      factor-alpha and interleukin-1beta) were determined. Dihydrocucurbitacin B
      modified the evolution of the clinical symptoms, reducing the swelling and bone
      and tissue damage along with the development of the disease, modifying the cell
      infiltration and the expression of both nitric oxide synthase-2 and
      cyclooxygenase-2. In addition, it decreased the tumor necrosis factor-alpha and
      interleukin-1beta production in lymphocytes, but did not modify it in
      macrophages.

PMID- 16443216
TI  - Regulation of psychostimulant-induced preprodynorphin, c-fos and zif/268
      messenger RNA expression in the rat dorsal striatum by mu opioid receptor
      blockade.
AB  - Several studies have shown that psychostimulants can induce differential
      immediate early gene and neuropeptide expression in the patch versus matrix
      compartments of dorsal striatum. The patch compartment contains a high density of
      mu opioid receptors and activation of these receptors may contribute to
      psychostimulant-induced gene expression in the patch versus matrix compartments
      of dorsal striatum. However, the contribution of mu opioid receptor activation to
      psychostimulant-induced changes in gene expression in the patch compartment of
      dorsal striatum has not been examined. The current study examined the role of mu
      opioid receptors in psychostimulant induction of preprodynorphin, c-fos and
      zif/268 messenger RNA expression in the patch versus matrix compartments of
      dorsal striatum. Male Sprague-Dawley rats were treated with the mu opioid
      receptor antagonist, clocinnamox (1 mg/kg, s.c.), 24 h prior to treatment with
      cocaine (30 mg/kg, i.p.) or methamphetamine (15 mg/kg, s.c.) and sacrificed 45
      min or 3 h later. Mu opioid receptor antagonism blocked psychostimulant-induced
      preprodynorphin messenger RNA expression only in the rostral patch compartment,
      whereas psychostimulant-induced zif/268 messenger RNA expression in the patch and
      matrix compartments was attenuated throughout the dorsal striatum. Clocinnamox
      pretreatment had no effect on stimulant-induced increases in c-fos expression.
      These data suggest that mu opioid receptor activation plays a specific role in
      psychostimulant-induced preprodynorphin messenger RNA expression in the rostral
      patch compartment and zif/268 messenger RNA expression throughout dorsal
      striatum.

PMID- 16443218
TI  - TGF-beta1 siRNA suppresses the tubulointerstitial fibrosis in the kidney of
      ureteral obstruction.
AB  - TGF-beta1 has been known as an important factor in tubulointerstitial fibrosis
      which is a common process in most progressive renal diseases. We hypothesized
      that the interstitial fibrosis could be prevented by abolishing TGF-beta1
      function in unilateral ureteral obstruction (UUO)-induced renal fibrosis. shRNA
      vectors were generated to suppress TGF-beta1 expression at a high glucose
      concentration which allowed the maximal induction of TGF-beta1 in primary rat
      mesangial cells. An shRNA vector, designated shTB1d, significantly suppressed TGF
      beta1 in both transcriptional and translational levels in vitro cultured cells
      and in vivo fibrosis-induced mouse kidney, accompanied by the suppression of
      target genes (e.g., type I collagen and PAI-1) of TGF-beta1. Furthermore, the
      shTB1d suppressed the expression of TGF-beta1 and type I collagen in
      tubulointerstitial cells until day 7 after UUO-induced fibrosis, but none- or
      vector-treated mice maintained their expression, suggesting that the TGF-beta1
      shRNA delays the process of renal fibrosis in UUO mouse model. This work would
      provide a valuable tool to prevent tubulointerstitial fibrosis using RNA
      interference strategy.

PMID- 16443219
TI  - Nuclear localisation of endogenous SUMO-1-modified PDGF-C in human thyroid tissue
      and cell lines.
AB  - We investigated post-translational modification and subcellular localisation of
      endogenous platelet-derived growth factor-C (PDGF-C) in human thyroid papillary
      carcinomas (PTC), non-neoplastic thyroid tissues, and a selection of cultured
      cell lines. PDGF-C expressed nuclear localisation in 95% of all tested cell types
      in culture and in 10% of the thyrocytes from both PTC and non-neoplastic tissue.
      The cell lines expressed two forms of full-length PDGF-C, approximately 39 and
      approximately 55 kDa, in cell membrane and cytosol, while the approximately 55
      kDa form dominated in the nucleus where it was partly chromatin-associated. The
      approximately 55 kDa form was post-translationally modified by SUMO-1. The
      putative PDGF-C SUMOylation site is the surface exposed (314)lysine part of a
      positively charged loop ((312)RPKTGVRGLHK(322)) with characteristics of a nuclear
      localisation signal. The tissue thyrocytes expressed a non-SUMOylated
      approximately 43 kDa and the 55 kDa PDGF-C. The SUMO-1 modified approximately 55
      kDa PDGF-C expression was low in PTC where the approximately 43 kDa PDGF-C
      dominated. This is in contrast to non-neoplastic tissue and cultured cells where
      the SUMOylated approximately 55 kDa PDGF-C was strongly expressed. Our data
      provide novel evidence for nuclear localisation of PDGF-C, post-translational
      modification by SUMOylation and the expression of a novel form of PDGF-C in human
      papillary thyroid carcinomas.

PMID- 16443217
TI  - Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL
      12p40 in mouse bone marrow-derived dendritic cells infected with Legionella
      pneumophila.
AB  - Delta-9-tetrahydrocannabinol (THC) injection suppresses serum interleukin-12 (IL
      12) levels in Legionella pneumophila-infected mice. Dendritic cells are a major
      producer of IL-12 and mouse, bone marrow-derived dendritic cell cultures produced
      high levels of the IL-12p40 following L. pneumophila infection. Treatment with
      THC suppressed this cytokine response in a concentration-dependent manner and the
      endocannabinoid, 2-arachidonoyolglycerol, less potently suppressed cytokine
      production. Dendritic cells expressed mRNA for cannabinoid receptor 1 (CB(1)),
      cannabinoid CB(2) receptor, and vanilloid receptor 1 (TRPV1) and the addition of
      the G(i) inhibitor, pertussis toxin, completely attenuated suppression induced by
      3 and 6 muM THC but not by 10 muM THC. Furthermore, THC suppression was partially
      attenuated in dendritic cells from cannabinoid CB(1) receptor and CB(2) receptor
      knockout mice and in dendritic cells co-treated with THC and cannabinoid receptor
      antagonists. Cytokine suppression was not attenuated by pretreatment with the
      TRPV1 antagonist, capsazepine. These results suggest that THC-induced suppression
      of serum IL-12 is partly due to a suppression of IL-12 production by dendritic
      cells and that G(i) signaling and cannabinoid receptors, but not TRPV1, are
      involved in this suppressive effect.

PMID- 16443220
TI  - Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed
      in chronic myeloid leukemia and interacts with Bcr-Abl.
AB  - A novel C3G isoform, designated p87C3G, lacking the most amino terminal region of
      the cognate protein has been found to be overexpressed in two CML cell lines,
      K562 and Boff 210, both expressing Bcr-Abl p210. p87C3G expression is also highly
      augmented in patients diagnosed with chronic myeloid leukemia (CML) Ph+, in
      comparison with healthy individuals, and returns to basal levels after treatment
      with STI571. p87C3G co-immunoprecipitates with both CrkL and Bcr-Abl in CML cell
      lines and co-immunoprecipitation between p87C3G and Bcr-Abl was also detected in
      primary cells from CML patients. These interactions have been confirmed by in
      vitro pull down experiments. The interaction between p87C3G and Bcr-Abl involves
      the SH3-binding domain of p87C3G and the SH3 domain of Abl and depends mostly on
      the first polyproline region of p87C3G. Furthermore, we also demonstrated that
      p87C3G is phosphorylated in vitro by a Bcr-Abl-dependent mechanism. These results
      indicate that p87C3G overexpression is linked to CML phenotype and that p87C3G
      may exert productive functional interactions with Bcr-Abl signaling components
      suggesting the implication of this C3G isoform in the pathogenesis of chronic
      myeloid leukemia.

PMID- 16443221
TI  - Remodeling of synaptic structures in the motor cortex following spinal cord
      injury.
AB  - After spinal cord injury (SCI), structural reorganization occurs at multiple
      levels of the motor system including the motor cortex, and this remodeling may
      underlie recovery of motor function. The present study determined whether SCI
      leads to a remodeling of synaptic structures in the motor cortex. Dendritic
      spines in the rat motor cortex were visualized by confocal microscopy in fixed
      slices, and their density and morphology were analyzed after an overhemisection
      injury at C4 level. Spine density decreased at 7 days and partially recovered by
      28 days. Spine head diameter significantly increased in a layer-specific manner.
      SCI led to a higher proportion of longer spines especially at 28 days, resulting
      in a roughly 10% increase in mean spine length. In addition, filopodium-like long
      dendritic protrusions were more frequently observed after SCI, suggesting an
      increase in synaptogenic events. This spine remodeling was accompanied by
      increased expression of polysialylated neural cell adhesion molecule, which
      attenuates adhesion between the pre- and postsynaptic membranes, in the motor
      cortex from as early as 3 days to 2 weeks after injury, suggesting a decrease in
      synaptic adhesion during the remodeling process. These results demonstrate time
      dependent changes in spine density and morphology in the motor cortex following
      SCI. This synaptic remodeling seems to proceed with a time scale ranging from
      days to weeks. Elongation of dendritic spines may indicate a more immature and
      modifiable pattern of synaptic connectivity in the motor cortex being reorganized
      following SCI.

PMID- 16443222
TI  - Transplantation of NGF secreting primary monocytes counteracts NMDA-induced cell
      death of rat cholinergic neurons in vivo.
AB  - Cholinergic neurons of the basal forebrain degenerate in Alzheimer's disease.
      Nerve growth factor (NGF) is so far the most potent molecule to counteract this
      neurodegeneration; however, the delivery of NGF into the brain is very difficult.
      The aim of the present study was to observe, if transplanted primary monocytes
      secreting NGF may counteract N-methyl-D-aspartate (NMDA)-induced cell death of
      cholinergic neurons of the basal nucleus of Meynert (nBM) in vivo. Monocytes were
      purified by indirect magnetic separation from rat blood. Recombinant NGF was
      introduced into cells using the novel protein-delivery reagent BioPORTERtrade
      mark and secretion of NGF was measured by ELISA. Monocytes secreted approximately
      4000 pg NGF/day/1 x 10(6) cells. Injection of monocytes onto organotypic brain
      slices of the nBM in vitro protected cholinergic neurons against cell death. When
      monocytes were transplanted in vivo into the lateral ventricle, the cells
      survived for up to 7 days and counteracted the NMDA-induced cell death of
      cholinergic neurons. In conclusion, primary monocytes secreting recombinant NGF
      are useful to deliver NGF directly into the brain.

PMID- 16443223
TI  - Concentrations of extracellular free zinc (pZn)e in the central nervous system
      during simple anesthetization, ischemia and reperfusion.
AB  - "Free Zn2+" (rapidly exchangeable Zn2+) is stored along with glutamate in the
      presynaptic terminals of specific specialized (gluzinergic) cerebrocortical
      neurons. This synaptically releasable Zn2+ has been recognized as a potent
      modulator of glutamatergic transmission and as a key toxin in excitotoxic
      neuronal injury. Surprisingly (despite abundant work on bound zinc), neither the
      baseline concentration of free Zn2+ in the brain nor the presumed co-release of
      free Zn2+ and glutamate has ever been directly observed in the intact brain in
      vivo. Here, we show for the first time in dialysates of rat and rabbit brain and
      human CSF samples from lumbar punctures that: (i) the resting or "tonic" level of
      free Zn2+ signal in the extracellular fluid of the rat, rabbit and human being is
      approximately 19 nM (95% range: 5-25 nM). This concentration is 15,000-fold lower
      than the "300 microM" concentration which is often used as the "physiological"
      concentration of free zinc for stimulating neural tissue. (ii) During ischemia
      and reperfusion in the rabbit, free zinc and glutamate are (as has often been
      presumed) released together into the extracellular fluid. (iii) Unexpectedly,
      Zn2+ is also released alone (without glutamate) at a variable concentration for
      several hours during the reperfusion aftermath following ischemia. The source(s)
      of this latter prolonged release of Zn2+ is/are presumed to be non-synaptic and
      is/are now under investigation. We conclude that both Zn2+ and glutamate
      signaling occur in excitotoxicity, perhaps by two (or more) different release
      mechanisms.

PMID- 16443225
TI  - Cervical gland area as an ultrasonographic marker for preterm delivery.
AB  - OBJECTIVE: To assess the association between spontaneous preterm delivery (SPTD)
      in the general population and the measurement of the cervix length, cervical
      funneling, and absence of the cervical gland area (CGA). METHOD: A prospective
      cohort of 338 women carrying uncomplicated pregnancies was evaluated by
      transvaginal sonography between 21 and 24 weeks' gestation. RESULTS: Measurement
      of cervical length with less than 20 mm and the presence of cervical funneling
      presented a statistically significant association with SPTD before 35 weeks. The
      non-detection of CGA demonstrated a strong association with SPTD before 37 weeks'
      (p < 0.001; OR = 194.5) and before 35 weeks' gestation (p < 0.001; OR = 129.6).
      The multiple logistic regression analysis suggested the non-detection of CGA as
      the only variable to reveal statistically significance association with SPTD.
      CONCLUSION: The results seem to indicate that the absence of CGA can be a new and
      important ultrasound marker for SPTD, to be confirmed by future multicenter
      investigations.

PMID- 16443224
TI  - Cell therapy of pain: Characterization of human fetal chromaffin cells at early
      adrenal medulla development.
AB  - Adult adrenal chromaffin cells are being utilized for therapeutic
      transplantation. With the prospect of using fetal chromaffin cells in pain
      therapy, we studied their phenotype, proliferative power, function, and growth in
      vitro and in situ in order to determine the optimal time for implantation.
      Between 7 and 10 gestational weeks (GW), we isolated, in vitro, two types of
      chromaffin cells with a noradrenergic phenotype akin to that observed, in situ.
      Among the adherent chromaffin cells first observed in vitro, only a few samples
      expressed met-enkephalin, whereas almost all the neurosphere-like colonies, which
      appeared later, expressed it. However, neither of the two types of populations
      expressed an adrenergic phenotype in line with that observed in situ. At the
      upper limits of the voluntary abortion period authorized in France, this
      phenotype (12 GW) and met-enkephalin expression (13 GW) were evidenced in situ.
      For the first time in man, we demonstrate the secretion of noradrenaline in vitro
      by the two populations of cells. Consistent with this result, we also noted
      dopamine beta hydroxylase (DbetaH) mRNA expression in vitro and in situ within
      this period. These observations on the expression of these biological factors
      indicate that 9-10 GW would be the best stage for sampling these cells for
      preclinical transplantation experiments.

PMID- 16443227
TI  - The course of infections and pathology in immunomodulated NOD/LtSz-SCID mice
      inoculated with Plasmodium falciparum laboratory lines and clinical isolates.
AB  - Human chimeras are potentially invaluable models for hemoprotozoan parasites such
      as Plasmodium falciparum. The work presented assesses the susceptibility of
      immunomodulated NOD/LtSz-SCID mice to genetically distinct P. falciparum
      parasites. To this end, mice grafted with human erythrocytes were inoculated with
      two P. falciparum laboratory lines, 3D7 and Dd2 and four clinical isolates,
      ISCIII-230, ISCIII-231, ISCIII-381 and ISCIII-399. The results showed that,
      without a previous period of parasite adaptation, 100% of the inoculated mice
      developed an infection, generally self-limited, though some mice died. The
      parasitemias ranged from 0.05 to 8% and lasted an average of 19 days (15-26 days)
      depending on the line or isolate studied. Sexual forms of different maturity,
      stage II-IV and mature gametocytes were observed in the peripheral blood of mice
      in 22, 50, 25, 72 and 80% of the mice infected with Dd2, ISCIII-399, ISCIII-230,
      ISCIII-231 and ISCIII-381 isolates, respectively. The study of the clinical
      symptoms, the haematological parameters and the histopathological changes in the
      infected mice showed that most of the malaria features were present in the
      infected mice except that the sequestration of infected erythrocytes was absent
      or at most a minor phenomenon, as also indicated by the presence of mature forms
      of the parasites in the peripheral blood. This study shows that the human
      chimeras allow the complete asexual and sexual erythrocytic cycle of different P.
      falciparum lines and clinical isolates to be observed in vivo. It opens a new way
      to investigate any parasite population in terms of infectivity, transmission, and
      drug resistance.

PMID- 16443226
TI  - Trypanosoma cruzi 5S rRNA arrays define five groups and indicate the geographic
      origins of an ancestor of the heterozygous hybrids.
AB  - Isolates of the etiological agent of Chagas disease, Trypanosoma cruzi, have been
      subdivided into six subgroups referred to as discrete typing units. The subgroups
      are related through two distinct hybridisation events: representatives of
      homozygous discrete typing units I and IIb fused to form discrete typing units
      IIa and IIc, whose homozygous genotypes have features of both ancestral types; a
      second fusion between strains of homozygous discrete typing units IIb and IIc
      created the heterozygous hybrid strains discrete typing units IId and IIe. The
      intergenic region of the tandemly repeated 5S rRNA array displays four variant
      sequence classes, allowing the discrimination of five discrete typing units. The
      genome project reference strain, CL Brener, is a hybrid discrete typing unit IIe
      strain that contains both discrete typing unit IIb and IIc classes of 5S rRNA
      repeats in distinct arrays present on different chromosomes. The CL Brener
      discrete typing unit IIb-type array contains approximately 193 repeated units, of
      which about one-third contain a 129 bp sequence that replaces a majority of the
      5S rRNA sequence. The 129 bp 'invader' sequence was detected within the arrays of
      all hybrid discrete typing unit IId and IIe strains and in a subset of discrete
      typing unit IIb strains. This array invader replaces the internal promoter
      elements conserved in 5S rRNA. The discrete typing unit IIb Esmeraldo strain
      contains approximately 135 repeats and shows a region of homology to the array
      invader in the 5' flank of the array, but no evidence of the invading sequence
      element within the array. A survey of additional discrete typing unit IIb strains
      revealed a split within the subgroup, in which some strains contained invaded
      arrays and others were homogeneous for the 5S rRNA. The putative discrete typing
      unit IIb ancestor of the hybrid discrete typing units IId and IIe more closely
      resembles the extant Bolivian/Chilean IIb isolates than the Brazilian IIb
      isolates based on the correlation with the array invader.

PMID- 16443228
TI  - Peptidyl-prolyl cis-trans isomerases (immunophilins) and their roles in parasite
      biochemistry, host-parasite interaction and antiparasitic drug action.
AB  - Immunophilin is the collective name given to the cyclophilin and FK506-binding
      protein families. As the name suggests, these include the major binding proteins
      of certain immunosuppressive drugs: cyclophilins for the cyclic peptide
      cyclosporin A and FK506-binding proteins for the macrolactones FK506 and
      rapamycin. Both families, although dissimilar in sequence, possess peptidyl
      prolyl cis-trans isomerase activity in vitro and can play roles in protein
      folding and transport, RNA splicing and the regulation of multi-protein complexes
      in cells. In addition to enzymic activity, many immunophilins act as molecular
      chaperones. This property may be conferred by the isomerase domain and/or by
      additional domains. Recent years have seen a great increase in the number of
      known immunophilin genes in parasitic protozoa and helminths and in many cases
      their products have been characterised biochemically and their temporal and
      spatial expression patterns have been examined. Some of these genes represent
      novel types: one example is a Toxoplasma gondii gene encoding a protein with both
      cyclophilin and FK506-binding protein domains. Likely roles in protein folding
      and oligomerisation, RNA splicing and sexual differentiation have been suggested
      for parasite immunophilins. In addition, unexpected roles in parasite virulence
      (Mip FK506-binding protein of Trypanosoma cruzi) and host immuno-modulation (e.g.
      18-kDa cyclophilin of T. gondii) have been established. Furthermore, in view of
      the potent antiparasitic activities of cyclosporins, macrolactones and non
      immunosuppressive derivatives of these compounds, immunophilins may mediate drug
      action and/or may themselves represent potential drug targets. Investigation of
      the mechanisms of action of these agents may lead to the design of potent and
      selective antimalarial and other antiparasitic drugs. This review discusses the
      properties of immunophilins in parasites and the 'animal model'Caenorhabditis
      elegans and relates these to our understanding of the roles of these proteins in
      cellular biochemistry, host-parasite interaction and the antiparasitic mechanisms
      of the drugs that bind to them.

PMID- 16443230
TI  - Force depression following muscle shortening in sub-maximal voluntary
      contractions of human adductor pollicis.
AB  - Mechanical properties of skeletal muscles are often studied for controlled,
      electrically induced, maximal, or supra-maximal contractions. However, many
      mechanical properties, such as the force-length relationship and force
      enhancement following active muscle stretching, are quite different for maximal
      and sub-maximal, or electrically induced and voluntary contractions. Force
      depression, the loss of force observed following active muscle shortening, has
      been observed and is well documented for electrically induced and maximal
      voluntary contractions. Since sub-maximal voluntary contractions are arguably the
      most important for everyday movement analysis and for biomechanical models of
      skeletal muscle function, it is important to study force depression properties
      under these conditions. Therefore, the purpose of this study was to examine force
      depression following sub-maximal, voluntary contractions. Sets of isometric
      reference and isometric-shortening-isometric test contractions at 30% of maximal
      voluntary effort were performed with the adductor pollicis muscle. All reference
      and test contractions were executed by controlling force or activation using a
      feedback system. Test contractions included adductor pollicis shortening over 10
      degrees, 20 degrees, and 30 degrees of thumb adduction. Force depression was
      assessed by comparing the steady-state isometric forces (activation control) or
      average electromyograms (EMGs) (force control) following active muscle shortening
      with those obtained in the corresponding isometric reference contractions. Force
      was decreased by 20% and average EMG was increased by 18% in the shortening test
      contractions compared to the isometric reference contractions. Furthermore, force
      depression was increased with increasing shortening amplitudes, and the relative
      magnitudes of force depression were similar to those found in electrically
      stimulated and maximal contractions. We conclude from these results that force
      depression occurs in sub-maximal voluntary contractions, and that force
      depression may play a role in the mechanics of everyday movements, and therefore
      may have to be considered in biomechanical models of human movement.

PMID- 16443229
TI  - Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4
      and 2 in vivo.
AB  - In addition to lipid lowering effects, statins appear to have pleiotropic
      immunomodulatory properties. As they particularly affect monocyte functions, we
      tested the influence of statin treatment on the monocyte activating toll-like
      receptors (TLR) 4 and 2 in response to lipopolysaccharides (LPS) in vivo. In this
      double-blind, placebo-controlled study, 20 healthy, male subjects were randomized
      to receive either simvastatin (80 mg/day) or placebo for 4 days before
      intravenous LPS administration (20 IU/kg). Simvastatin did not influence the
      increase in TLR transcripts after LPS administration measured in mRNA isolated
      from whole blood by quantitative RT-PCR. In contrast, the parallel upregulation
      of TLR4 and TLR2 on the surface of monocytes determined by flow cytometry was
      attenuated by more than half after LPS challenge (P<0.02). Suppressed TLR4 and
      TLR2 expression was associated with diminished circulating concentrations of
      tumor necrosis factor-alpha and monocyte chemoattractant protein-1. In
      conclusion, high-dose simvastatin pretreatment blunted TLR4 and TLR2 expression
      on monocytes in a human endotoxemia model on a posttranscriptional level. This
      suppressive effect of statins on key receptors of the innate immunity which was
      associated with a reduction of effector cytokines reveals a potential mechanism
      for their beneficial effects in sepsis and cardiovascular disease.

PMID- 16443231
TI  - Enantioselective high-performance liquid chromatographic separation of N
      methyloxycarbonyl unsaturated amino acids on macrocyclic glycopeptide stationary
      phases.
AB  - This paper describes the enantiomeric resolution of a series of unsaturated N
      methyloxycarbonyl-alpha-H-alpha-amino acids (N-MOC-alpha-amino acids) on
      macrocyclic glycopeptide stationary phases by means of high-performance liquid
      chromatography (HPLC). Three types of glycopeptide phases, i.e. Chirobiotic T, V
      and R, were evaluated in both reversed-phase (RP) and polar ionic mode (PIM). The
      best results in terms of enantioselectivity and resolution were obtained on
      Chirobiotic R phase, with the PIM mobile phase giving the highest resolution per
      min. Investigation of the pH of the reversed-phase mobile phase in the pH range
      4.1-5.9 showed little effect on enantioselectivity. The method was applied for
      monitoring the conversion and product enantiomeric excess of an enzymatic
      hydrolysis reaction using N-MOC-alpha-H-alpha-amino acid esters as substrate.

PMID- 16443232
TI  - Capillary electrophoretic analysis of flavonoids in single-styled hawthorn
      (Crataegus monogyna Jacq.) ethanolic extracts.
AB  - Flavonoids are an important group of natural compounds, which can prevent
      coronary heart disease and have antioxidant properties. Hawthorn is a well known
      and widely used medicinal plant due to its cardiotonic activity. Previous studies
      refer mostly to the HPLC analysis of the flavonoids: vitexin, quercetin,
      hyperoside, oligomeric procyanidins, which appear to be primarily responsible for
      the cardiac action of the plant. Aqueous ethanolic extracts of single-styled
      hawthorn (Crataegus monogyna Jacq., f.: Rosaceae Juss.) leaves and sprouts were
      analyzed by means of capillary zone electrophoresis (CZE). Influence of
      vegetation period on the extract qualitative composition and flavonoids
      quantities was evaluated. Sample preparation by extraction using different
      concentration of aqueous ethanol (40-96%, v/v) and the influence of extractant
      composition on the recovery of flavonoids are discussed in detail. The results
      obtained using CZE are compared to the results of spectrophotometric and HPLC
      analysis of the extracts. The effect of storage conditions of extracts (solar
      irradiation, temperature and duration) on degradation of flavonoids was
      investigated.

PMID- 16443234
TI  - Vapor pressure determinations of 8-2 fluorortelomer alcohol and 1-H
      perfluorooctane by capillary gas chromatography Relative retention time versus
      headspace methods.
AB  - Two distinctly different capillary gas chromatographic methods were used to
      determine the vapor pressure of 8-2 fluorotelomer alcohol (8-2 FTOH) and 1-H
      perfluoroheptane at several temperatures. For measurements employing the relative
      retention-time method, a short polymethylsiloxane column was used from 25 to 65
      degrees C. For the 8-2 FTOH, hydrocarbon alcohols and perfluoroalcohols were used
      as reference standards. For 1-H perfluoroheptane, hydrocarbons were used as
      reference standards. Vapor pressure estimates could differ by as much as an order
      of magnitude compared to published results determined by other
      (nonchromatographic) methods. This variance may be a function of solvent-solute
      interactions within the gas chromatographic column and the infinite dilution
      assumption, both used in the relative retention method. For comparison, data were
      also gathered using headspace gas chromatography (GC) with atomic emission
      detection (AED). The results from this novel GC/AED method were consistent with
      prior nonchromatographic results. A discussion of why headspace is the preferred
      technique for the determination of vapor pressure for fluorinated compounds is
      presented.

PMID- 16443233
TI  - Determination of ethephon residues in water by gas chromatography with cubic mass
      spectrometry after ion-exchange purification and derivatisation with N-(tert
      butyldimethylsilyl)-N-methyltrifluoroacetamide.
AB  - An analytical method has been developed for the determination of residues of
      ethephon (2-chloroethyl phosphonic acid) in drinking and surface water. The
      procedure is based on de-ionisation with an anion/cation-exchange resin, solid
      phase extraction by means of anion-exchange polystyrene-divinylbenzene extraction
      disks, elution with a mixture of methanol and 10 M hydrochloric acid (98/2, v/v),
      redisolution into acetonitrile after evaporation and silylation with N-(tert
      butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA). Quantification is
      performed by gas chromatography with ion-trap cubic mass spectrometric detection
      in the electron impact mode (GC-EI-MS3). Method validation was conducted using
      samples of mineral, tap, and river water that were fortified with ethephon at
      concentration levels ranging from 0.1 to 1.0 microg/L. The mean recovery from all
      the fortified samples (n = 36) amounted to 88% with a relative standard deviation
      of 17%. The method, therefore, was shown to allow accurate determination of
      ethephon residues in drinking and surface water with a limit of quantification of
      0.1 microg/L.

PMID- 16443235
TI  - Adsorption of guar gum onto quartz from dilute mixed electrolyte solutions.
AB  - The effect of potassium, sodium, calcium, magnesium, and hydrogen cations on
      adsorption of guar gum onto quartz was investigated at natural pH. The role of
      the background ions was analyzed in terms of their water-structure making or
      breaking capabilities. In dilute solutions (0.01 mol/L) of structure-makers
      (NaCl, HCl, CaCl2, and MgCl2), the guar gum adsorption density did not change
      compared to the adsorption densities obtained in distilled water. Potassium, the
      only structure-breaking ion (chaotrope) among the tested cations, significantly
      enhanced guar gum adsorption. The results obtained in mixed electrolytes
      demonstrate that the strong structure-breaking properties of K+ overcome any
      contributions from weak structure making ions (kosmotropes), and guar gum
      adsorption remains at the levels observed in KCl alone. Only when strongly
      hydrated Mg2+ ions are mixed with KCl, the overall effect becomes additive and
      the influence of potassium is proportionally reduced by increasing concentrations
      of magnesium cations. In this approach, guar gum adsorption on quartz is viewed
      as a competition between polysaccharide and water molecules for silanol surface
      sites. The hydration of the quartz surface inhibits the adsorption process but
      the competition equilibrium, and hence polysaccharide adsorption, can be affected
      by the presence of chaotropes or kosmotropes.

PMID- 16443236
TI  - Firefly luciferase terminally degraded by mild heat exposure: implications for
      reporter assays.
AB  - Luciferase reporter constructs are an accurate method of assessing gene promoter
      activity and vectors constitutively expressing luciferase are useful in
      quantifying transfection efficiency. Common methodologies for examining the
      induction of the heat shock (stress) response require exposure of cells
      transfected with luciferase-expressing vectors to a mild heat stress. Here we re
      examine the under-recognised phenomenon that luciferase is exquisitely sensitive
      to small temperature changes. In cells subjected to mild heat exposure following
      transfection with both luciferase and beta-galactosidase reporter vectors, a
      marked reduction in luciferase activity was observed compared with beta
      galactosidase activity. On exposing recombinant firefly luciferase to small
      increases in temperature in vitro, a time and temperature dependent decrease in
      luciferase activity was demonstrated. Loss of luciferase activity following mild
      heat exposure will result in misinterpretation of reporter activity. This vastly
      underappreciated effect is worthy of further emphasis and luciferase reporter
      vectors should be used with caution in protocols that involve exposure to
      temperatures outside the physiological range.

PMID- 16443237
TI  - An ultrastructural and molecular study of Tubulinosema kingi Kramer
      (Microsporidia: Tubulinosematidae) from Drosophila melanogaster (Diptera:
      Drosophilidae) and its parasitoid Asobara tabida (Hymenoptera: Braconidae).
AB  - Tubulinosema kingi is a pathogen of Drosophila spp. that was originally described
      40 years ago. Although Drosophila melanogaster is widely used as a model organism
      for biological research, only limited data about microsporidia infecting
      Drosophila have been published so far and very little is known about the
      ultrastructure of T. kingi. In this study, we present the results of
      ultrastructural and molecular examinations of T. kingi. The whole life cycle took
      place in direct contact with the host cell cytoplasm and all examined life cycle
      stages contained a diplokaryon. Very few membrane elements were present in early
      merogonial stages, but their number and order of arrangement increased as the
      life cycle proceeded. The cell membrane of meronts had a surface coat of tubular
      elements that encircled the cell. Later, numerous electron-dense strands without
      any ornamentation accumulated on the plasma membrane, indicating that cells had
      entered sporogony. The cell membrane of sporonts was covered by electron-dense
      material. The polar filament in the spores was slightly anisofilar with the last
      three or four coils being smaller in diameter. The polar filament has 10 to 14
      coils which were arranged predominantly in a single row, but in many spores, one
      winding of the coiled polar filament was located inside the outer coils. In some
      spores, the polar filament was irregularly arranged in two or even three rows.
      Molecular analysis showed that all Tubulinosema spp. are closely related and form
      a clade of their own that is distinct from the Nosema/Vairimorpha clade. All
      these ultrastructural and molecular features are in concordance with the family
      Tubulinosematidae and the genus Tubulinosema which reinforces the recent
      reclassification of this microsporidium.

PMID- 16443238
TI  - Crucial roles of both flanking sequences in silencing of the hilA promoter in
      Salmonella enterica.
AB  - The hilA gene on the Salmonella enterica pathogenicity island-1 encodes the key
      transcriptional regulator of host cell invasion. Transcription of hilA is
      regulated by numerous physiological signals, including repression under low
      osmolarity conditions. To investigate the osmotic control of hilA transcription,
      promoter truncations that remove sequences flanking the hilA promoter were
      examined. Expression of the minimal hilA core promoter (-55 to +90, relative to
      the transcription start site) was 57-times higher than the intact promoter (-242
      to +505) in the absence of osmotic stress. Both flanking sequences contributed to
      the strong silencing effect, which was greatly relieved by the simultaneous loss
      of the two nucleoid-structuring proteins, H-NS and Hha. Mobility-shift assays
      revealed the presence of binding sites for the H-NS and Hha proteins, both
      upstream and downstream of the promoter. Either flanking region depressed
      expression when it was placed downstream of the lacUV5 promoter, and this
      inhibition was increased when the other flanking sequence was present upstream of
      the promoter. These results show that the hilA promoter is highly active without
      other transcription regulators. Its high activity is strongly depressed in low
      osmolarity conditions by the nucleoid-structuring proteins H-NS and Hha, possibly
      by formation of a repressive DNA loop. The hilA activators, HilD and HilC appear
      to overcome effects of downstream silencing region and disrupt repressive DNA
      loop. Action of activators requires contact with RNA polymerase from their DNA
      binding site, centered at position -77, relative to the hilA transcription start
      site.

PMID- 16443239
TI  - A new method in applying power spectral statistics to examine cardio-respiratory
      interactions in fish.
AB  - Power spectral analysis (PSA) provides a powerful tool for determining frequency
      oscillations in time signals, and it is accepted that mammals can show distinct
      components in the heart rate (fH) spectrum that are synchronous with ventilatory
      frequency (fV). Using similar signal processing techniques, these fundamental
      components at fV are not apparent in the spectrum calculated from fish fH. Here
      we compare conventional PSA on the R-R interval tachogram generated from ECG
      traces recorded in rats and fish, with PSA on the raw ECG waveform. The rat R-R
      tachogram showed a defined sigmoidal component, whereas the fish R-R tachogram
      was a more chaotic waveform. In agreement with the literature, PSA of these
      respective waveforms produced a component at the same frequency as ventilation in
      the rat, but of lower frequency than ventilation for the fish. Applying PSA to
      the rat ECG produced a spectrum with a fundamental component of similar frequency
      to that observed in the R-R tachogram spectrum, indicating that the latter
      adequately contained heart rate variability (HRV) oscillations. However, PSA of
      the ECG in fish contrasted with that from the R-R tachogram, with components
      observed in the latter spectrum being absent from the former. This suggests that
      the frequency components determined by PSA on the fish R-R tachogram were not
      true components, but were aliased (or folded-back) from higher up in the
      spectrum. Using established aliasing equations, recalculation of these peaks
      showed that their true frequency was similar to that of the ventilatory frequency
      for individual fish. The extent of cardio-respiratory interaction, resulting in
      fV < f(H/2) in rats but fV > f(H/2) in fish, is suggested to be the origin of the
      differences observed.

PMID- 16443240
TI  - Transport and toxic mechanism for aluminum citrate in human neuroblastoma SH-SY5Y
      cells.
AB  - Aluminum (Al) is thought to be a risk factor for neurodegenerative disorders, but
      the molecular mechanism has been not clarified yet. In this study, we examined
      how a transport system handled transport of Al citrate, the major Al species in
      brain, and effect of Al citrate treatment on expression of the transporter and on
      susceptibility to oxidative stress in human neuroblastoma SH-SY5Y cells. Uptake
      of Al citrate by the cells was temperature- and concentration-dependent, and
      inwardly-directed Na(+)-gradient-independent. Simultaneous application and
      preloading of L-cystine or L-glutamate inhibited and stimulated, respectively,
      the Al citrate uptake by SH-SY5Y cells, demonstrating kinetically that Na(+)
      independent L-cystine/L-glutamate exchanger, system Xc(-), is involved in its
      uptake. When the cells were treated with Al citrate, but not citrate, for 2
      weeks, but not a day, the expression of the transporter was decreased. Although
      the cell viability and glutathione content of the cells were not altered by the
      treatment with Al citrate alone, the number of dead cells among the Al citrate
      treated cells increased on exposure to oxidative stress caused by a glucose
      deprivation/reperfusion treatment. These findings demonstrate that Al citrate is
      a substrate for system Xc(-), and that chronic treatment with Al citrate causes
      downregulation of the transporter and increases the vulnerability of the cells to
      oxidative stress without a direct effect on the viability or GSH content.

PMID- 16443241
TI  - Adenosine as an active component of Antrodia cinnamomea that prevents rat PC12
      cells from serum deprivation-induced apoptosis through the activation of
      adenosine A(2A) receptors.
AB  - Antrodia cinnamomea (formerly named Antrodia camphorata) is a rare medicinal
      fungus. We previously reported that it exhibits antioxidative, vasorelaxative,
      anti-inflammatory, and anti-angiogenic effects. When serum deprivation-induced
      apoptosis in neuronal-like PC12 cells was used as a stress model, the extract of
      A. cinnamomea displayed effectiveness in preventing serum-deprived apoptosis.
      Since our previous data show that the extract of A. cinnamomea contains adenosine
      (ADO), we attempt to investigate if the active component is ADO and to identify
      its targeting site in this study. After pre-incubation with ADO deaminase,
      neither ADO nor the extract of A. cinnamomea exerted any protection,
      demonstrating that the active component of A. cinnamomea is ADO. Furthermore, an
      ADO A(2A) receptor (A(2A)-R) antagonist was used and was able to block the
      protective effects of ADO and the extract of A. cinnamomea, demonstrating that
      the ADO targeting site in this model is A(2A)-R. Taken together, the protective
      effect of A. cinnamomea is owed to its active component, ADO, which acts through
      activation of A(2A)-R to prevent serum deprivation-induced PC12 cell apoptosis.

PMID- 16443242
TI  - Influence of the anabolic-androgenic steroid nandrolone on cannabinoid
      dependence.
AB  - The identification of the possible factors that might enhance the risk of
      developing drug addiction and related motivational disorders is crucial to reduce
      the prevalence of these problems. Here, we examined in mice whether the exposure
      to the anabolic-androgenic steroid nandrolone would affect the pharmacological
      and motivational effects induced by Delta(9)-tetrahydrocannabinol (THC), the
      principal psychoactive component of Cannabis sativa. Mice received nandrolone
      using pre-exposure (during 14days before THC treatment) or co-administration (1h
      before each THC injection) procedures. Both nandrolone treatments did not modify
      the acute antinociceptive, hypothermic and hypolocomotor effects of THC or the
      development of tolerance after chronic THC administration. Nandrolone pre
      exposure blocked THC- and food-induced conditioned place preference and increased
      the somatic manifestations of THC withdrawal precipitated by the CB1 cannabinoid
      antagonist rimonabant (SR141617A). The aversive effects of THC were not changed
      by nandrolone. Furthermore, nandrolone pre-exposure attenuated the anxiolytic
      like effects of a low dose of THC without altering the anxiogenic-like effects of
      a high dose in the lit/dark box, open field and elevated plus-maze. Biochemical
      experiments showed that chronic nandrolone treatment did not modify CB1 receptor
      binding and GTP-binding protein activation in the caudate-putamen and cerebellum.
      Taken together, our results suggest that chronic nandrolone treatment alters
      behavioural responses related to cannabinoid addictive properties.

PMID- 16443243
TI  - Hepatitis C virus genotypes in southern Taiwan: prevalence and clinical
      implications.
AB  - The role of hepatitis C virus (HCV) genotypes in the development of
      hepatocellular carcinoma (HCC) is still controversial. To determine the
      distribution and clinical implications of HCV genotypes in southern Taiwan, we
      analysed 418 patients with chronic HCV infections. HCV genotypes were determined
      using an HCV Line Probe Assay. The predominant HCV genotype was 1b (45.5%),
      followed by 2a/2c (30.9%) and 2b (6.9%). The prevalence of genotype 1b in HCC
      patients (60.3%) was significantly higher than in those with liver cirrhosis
      (38.7%) and chronic hepatitis (38.7%) (P=0.003 and P<0.001, respectively).
      Patients with chronic HCV 2a/2c infection had higher alanine aminotransferase
      (ALT) levels than those with chronic HCV 1b infection (P<0.001). Univariate
      analysis revealed that disease severity was significantly correlated with older
      age, genotype 1b, lower ALT levels and lower viral load. Based on multiple
      logistic regression analysis, after adjusting for age and serum HCV RNA levels,
      HCV 1b infection was still a significant risk factor for HCC. In conclusion, the
      predominant genotypes in southern Taiwan were 1b and 2a/2c, and disease severity
      was associated with genotype 1b.

PMID- 16443244
TI  - Who is accessing antiretroviral therapy during national scale-up in Malawi?
AB  - Malawi is scaling-up provision of free antiretroviral therapy (ART) in the public
      sector. In the fourth quarter of 2004 and the first quarter of 2005, 3261 and
      4530 new patients, respectively, were started on ART. Of these patients,
      approximately 40% were male and 95% were adults aged > or =13 years. The age
      group data show that women who accessed ART were in general 10 years younger than
      men. Between 84% and 90% of patients were started on ART because of being
      clinically assessed as being in WHO stages III or IV, with the remainder started
      on ART owing to a low CD4 lymphocyte count. The number of tuberculosis (TB)
      patients started on ART was 351 (11% of ART patients) in the fourth quarter of
      2004 and 702 (15% of ART patients, and 16% of registered TB patients) in the
      first quarter of 2005. Twenty-nine pregnant women were referred to ART from
      prevention of mother-to-child transmission programmes in the first quarter of
      2005. Between 56% and 62% of patients were subsistence farmers, housewives or in
      business. Steady progress is being made with national scale-up, although more
      attention needs to be directed to children, pregnant women and patients with TB
      to improve their access to ART.

PMID- 16443245
TI  - Small bowel obstruction secondary to intestinal schistosomiasis.
AB  - Intestinal obstruction caused by chronic schistosomiasis infection is rare, with
      only 12 previously recorded cases in the literature. We report the first recorded
      case presenting to a European hospital. A 36-year-old Caucasian man, who was born
      and lived in the UK, presented with small bowel obstruction. He had visited China
      and Indonesia 8 years previously. At laparotomy, there was an obstructing
      inflammatory mass close to the ileocaecal junction and several small bowel
      strictures. Initially he was thought to have Crohn's disease. However, subsequent
      histology diagnosed intestinal schistosomiasis.

PMID- 16443246
TI  - Ultrasound verification of bladder damage is associated with known biomarkers of
      bladder cancer in adults chronically infected with Schistosoma haematobium in
      Ghana.
AB  - Long-term infection with urinary schistosomiasis has been associated with
      development of bladder cancer. However, bladder cancer is difficult to diagnose
      without invasive measures such as cystoscopy, thus there is little information on
      the epidemiological extent of the problem. Studies have been either case-control
      studies or case examinations in different geographical areas, estimating a
      schistosome-associated bladder cancer incidence of 3-4 cases per 100,000. We have
      used three indicators to examine the potential bladder cancer problem in an adult
      rural population in Ghana endemic for urinary schistosomiasis: (i)
      parasitological positivity; (ii) age prevalence of bladder damage from ultrasound
      scans; and (iii) detection of biomarkers associated with the presence of bladder
      cancer. Biomarkers were BLCA-4 test (urine) and nuclear morphometry or
      quantitative nuclear grading (QNG) of epithelial cells (urine sediment), which
      quantifies DNA ploidy status and nuclear morphometric descriptors, both of which
      can detect the presence of bladder cancer. Our data show an increasing
      association between age, severe bladder abnormalities and the occurrence of these
      biomarkers. Sixty-two of 73 cytopathology Papanicolaou-stained smears were seen
      to have squamous metaplasia. Although further investigations are needed, we
      suggest that schistosome-associated bladder cancer is an important public health
      concern in areas where Schistosoma haematobium is prevalent.

PMID- 16443247
TI  - Consecutive outbreaks of Vibrio cholerae O139 and V. cholerae O1 cholera in a
      fishing village near Karachi, Pakistan.
AB  - In July 2002 and June 2003, cholera outbreaks were detected by a diarrhoea
      surveillance system in a village outside Karachi, Pakistan. Specimens were
      culture confirmed. The first outbreak was caused by Vibrio cholerae O139 (n = 30)
      and the second outbreak by V. cholerae O1 (n = 39). Demographic and clinical
      features of patients were recorded and case-control studies were conducted
      following each outbreak. Clinical information was obtained for 29 of the 30
      patients in the first outbreak, and 2 of the patients in the second outbreak were
      either out of the area or lost to follow-up, leaving 29 and 37 cases in the
      analysis for the first and second outbreak, respectively. Eighteen (49%) of the
      37 V. cholerae O1 patients were under 2 years of age compared with 6 (21%) of the
      29 V. cholerae O139 patients (P = 0.02). Vibrio cholerae O139-infected patients
      were more likely to be febrile (16/29) than those infected with V. cholerae O1
      (2/37; P<0.001). A household contact with cholera was a risk factor in both
      outbreaks; water source was a risk factor in the first outbreak only.
      Geographically, cases were clustered during the first outbreak but not during the
      second. Person-to-person contact and water reservoirs appear to be the main
      transmission routes for cholera in this setting.

PMID- 16443248
TI  - Alteration of the spontaneous systemic autoimmune disease in (NZB x NZW)F1 mice
      by treatment with thimerosal (ethyl mercury).
AB  - Inorganic mercury may aggravate murine systemic autoimmune diseases which are
      either spontaneous (genetically determined) or induced by non-genetic mechanisms.
      Organic mercury species, the dominating form of mercury exposure in the human
      population, have not been examined in this respect. Therefore, ethyl mercury in
      the form of thimerosal, a preservative recently debated as a possible health
      hazard when present in vaccines, was administered in a dose of 0.156-5 mg/L
      drinking water to female (NZB x NZW)F1 (ZBWF1) mice. These mice develop an age
      dependent spontaneous systemic autoimmune disease with high mortality primarily
      due to immune-complex (IC) glomerulonephritis. Five mg thimerosal/L drinking
      water (295 microg Hg/kg body weight (bw)/day) for 7 weeks induced glomerular,
      mesangial and systemic vessel wall IC deposits and antinuclear antibodies (ANA)
      which were not present in the untreated controls. After 22-25 weeks, the higher
      doses of thimerosal had shifted the localization of the spontaneously developing
      renal glomerular IC deposits from the capillary wall position seen in controls to
      the mesangium. The altered localization was associated with less severe
      histological kidney damage, less proteinuria, and reduced mortality. The effect
      was dose-dependent, lower doses having no effect compared with the untreated
      controls. A different effect of thimerosal treatment was induction of renal and
      splenic vessel walls IC deposits. Renal vessel wall deposits occurred at a dose
      of 0.313-5 mg thimerosal/L (18-295 microg Hg/kg bw/day), while splenic vessel
      wall deposits developed also in mice given the lowest dose of thimerosal, 0.156
      mg/L (9 microg Hg/kg bw/day). The latter dose is 3- and 15-fold lower than the
      dose of Hg required to induce vessel wall IC deposits in genetically susceptible
      H-2s mice by HgCl2 and thimerosal, respectively. Further studies on the exact
      conditions needed for induction of systemic IC deposits by low-dose organic
      mercurials in autoimmune-prone individuals, as well as the potential effect of
      these deposits on the vessel walls, are warranted.

PMID- 16443249
TI  - Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice.
AB  - Atrazine is a widely used herbicide applied to corn, sugar and other crops as a
      broad leaf weed inhibitor. Using the Balb/c mouse model, we have determined that
      prenatal/lactational exposure to atrazine alters adult immune function. Pregnant
      Balb/c dams were exposed subcutaneously for 21 days via time release pellets to
      700 microg per day of atrazine beginning between days 10 and 12 of pregnancy.
      Prenatal/Lactational exposure caused no overt physical malformations in the
      offspring and had no effect on the number of litters carried to term or the
      litter size. Upon reaching early adulthood (approximately 3 months of age), the
      state of their immune system was evaluated. There were no changes in body weight
      or in the organ to body weight ratio of the spleen. Additionally, no changes were
      observed in the number of CD8+ T cell, CD4+ T cell, or B220+ B cell
      subpopulations in the spleen. T cell function was assessed by measuring
      proliferation and cytolytic activity after in vitro allogeneic stimulation. Male
      mice which had been prenatally/lactationally exposed to atrazine had an increase
      in both T cell proliferation and cytolytic activity. The humoral immune response
      was assessed after immunization with heat killed Streptococcus pneumoniae (HKSP).
      There was a significant increase in the number of HKSP-specific IgM secreting B
      cells in the spleen of prenatal/lactational exposed male mice. Inasmuch as
      atrazine is a widespread environmental contaminant, this immunopotentiation
      raises concerns that it may potentiate clinical diseases, such as autoimmune
      disease and hypersensitivity, and needs to be carefully monitored and studied.

PMID- 16443250
TI  - Protection from the toxicity of diisopropylfluorophosphate by adeno-associated
      virus expressing acetylcholinesterase.
AB  - Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and
      nerve agents. Their acute toxicity is attributed to inhibition of
      acetylcholinesterase (AChE, EC 3.1.1.7) in nerve synapses. Our goal was to find a
      new therapeutic for protection against OP toxicity. We used a gene therapy
      vector, adeno-associated virus serotype 2 (AAV-2), to deliver murine AChE to AChE
      /- mice that have no endogenous AChE activity. The vector encoded the most
      abundant form of AChE: exons 2, 3, 4, and 6. Two-day old animals, with an
      immature immune system, were injected. AChE delivered intravenously was expressed
      up to 5 months in plasma, liver, heart, and lung, at 5-15% of the level in
      untreated wild-type mice. A few mice formed antibodies, but antibodies did not
      block AChE activity. The plasma AChE was a mixture of dimers and tetramers. AChE
      delivered intramuscularly had 40-fold higher activity levels than in wild-type
      muscle. None of the AChE was collagen-tailed. No retrograde transport through the
      motor neurons to the central nervous system was detected. AChE delivered
      intrastriatally assembled into tetramers. In brain, the AAV-2 vector transduced
      neurons, but not astrocytes and microglia. Vector-treated AChE-/- mice lived
      longer than saline-treated controls. AChE-/- mice were protected from
      diisopropylfluorophosphate-induced respiratory failure when the vector was
      delivered intravenously, but not intrastriatally. Since vector-treated animals
      had no AChE activity in diaphragm muscle, protection from respiratory failure
      came from AChE in other tissues. We conclude that AChE scavenged OP and in this
      way protected the activity of butyrylcholinesterase (BChE, EC 3.1.1.8) in motor
      endplates.

PMID- 16443251
TI  - Estimated cancer risk of dioxins to humans using a bioassay and physiologically
      based pharmacokinetic model.
AB  - The health risk of dioxins and dioxin-like compounds to humans was analyzed
      quantitatively using experimental data and mathematical models. To quantify the
      toxicity of a mixture of three dioxin congeners, we calculated the new relative
      potencies (REPs) for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8
      pentachlorodibenzo-p-dioxin (PeCDD), and 2,3,4,7,8- pentachlorodibenzofuran
      (PeCDF), focusing on their tumor promotion activity. We applied a liver foci
      formation assay to female SD rats after repeated oral administration of dioxins.
      The REP of dioxin for a rat was determined using dioxin concentration and the
      number of the foci in rat liver. A physiologically based pharmacokinetic model
      (PBPK model) was used for interspecies extrapolation targeting on dioxin
      concentration in liver. Toxic dose for human was determined by back-estimation
      with a human PBPK model, assuming that the same concentration in the target
      tissue may cause the same level of effect in rats and humans, and the REP for
      human was determined by the toxic dose obtained. The calculated REPs for TCDD,
      PeCDD, and PeCDF were 1.0, 0.34, and 0.05 for rats, respectively, and the REPs
      for humans were almost the same as those for rats. These values were different
      from the toxic equivalency factors (TEFs) presented previously (Van den Berg, M.,
      Birnbaum, L., Bosveld, A.T.C., Brunstrom, B., Cook, P., Feeley, M., Giesy, J.P.,
      Hanberg, A., Hasegawa, R., Kennedy, S.W., Kubiak, T., Larsen, J.C., Rolaf van
      Leeuwen, F.X., Liem, A.K.D., Nolt, C., Peterson, R.E., Poellinger. L., Safe, S.,
      Schrenk, D., Tillitt, D, Tysklind, M., Younes, M., Waern, F., Zacharewski, T.,
      1998. Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and
      wildlife. Environ. Health Perspect. 106, 775-792). The relative risk of excess
      liver cancer for Japanese people in general was 1.7-6.5 x 10(-7) by TCDD only,
      and 2.9-11 x 10(-7) by the three dioxins at the present level of contamination.

PMID- 16443252
TI  - Feline foamy virus-mediated marker gene transfer: identification of essential
      genetic elements and influence of truncated and chimeric proteins.
AB  - Retroviral vectors derived from foamy or spumaretroviruses are considered
      promising tools for targeted gene delivery and vaccination purposes. In order to
      fully exploit this potential, we identified essential cis-acting sequences on the
      feline foamy virus (FFV) genome by constructing and analyzing a series of FFV
      based replication-deficient vector genomes. Cis-acting sequences essentially
      required for marker gene transfer were found to be localized at two sites on the
      FFV genome: (i) in the 5'-untranslated region and close to the gag ATG and (ii)
      in the central part of the pol gene. The presence of two cis-acting sequences and
      their relative location on the FFV genome are similar but not identical to the
      functionally corresponding elements described for simian and primate foamy
      viruses.

PMID- 16443254
TI  - Trace determination of 1-aminopropanone, a potential marker for wastewater
      contamination by liquid chromatography and atmospheric pressure chemical
      ionization-mass spectrometry.
AB  - 1-Aminopropanone (APR) is a volatile aminoketone of human origin that has been
      identified in raw sewage and surface waters. However, the traditional methodology
      for the determination of APR is extremely complicated and requires a skilled
      chemist to achieve consistent results. This investigation presents a novel and
      simple method for the analysis of APR by direct derivatization in aqueous media.
      APR is synthesized as its hydrochloride and derivatized using mercaptoethanol and
      o-phthalaldehyde. The product of reaction is separated on a 15 cm x 4.6 mm Luna C
      18 column (1 mL/min, 45:55 acetonitrile: Water) and detected using a single
      quadrupole mass spectrometer detector operated in atmospheric pressure chemical
      ionization (APCI) mode. Method detection limits as low as 100 nM were routinely
      obtained with a precision of 1.7%. Recoveries of APR were always found to be
      greater then 88% in surface and wastewater samples fortified at three different
      levels. However, despite the robustness of the method and the fact that APR was
      consistently detected in urine it was not present in a variety surface or
      wastewaters analyzed during the course of the study. These results pose a
      critical question on the use of APR as a tracer for human derived wastewaters.

PMID- 16443253
TI  - Structural characterization of the E2 glycoprotein from Sindbis by lysine
      biotinylation and LC-MS/MS.
AB  - Sindbis is an Alphavirus capable of infecting and replicating in both vertebrate
      and invertebrate hosts. Mature Sindbis virus particles consist of an inner capsid
      surrounded by a host-derived lipid bilayer, which in turn is surrounded by a
      protein shell consisting of the E1 and E2 glycoproteins. While a homolog of the
      E1 glycoprotein has been structurally characterized, the amount of structural
      data on the E2 glycoprotein is considerably less. In this study, the organization
      of the E2 glycoprotein was probed by surface biotinylation of intact virions. The
      virus remained fully infectious, demonstrating that the biotinylation did not
      alter the topology of the proteins involved in infection. Seven sites of
      modification were identified in the E2 glycoprotein (K70, K76, K97, K131, K149,
      K202, and K235), while one site of modification in the E1 glycoprotein (K16) was
      identified, confirming that the E1 protein is almost completely buried in the
      virus structure.

PMID- 16443255
TI  - Aged raw landfill leachate: membrane fractionation, O3 only and O3/H2O2
      oxidation, and molecular size distribution analysis.
AB  - Large molecular refractory organic compounds (i.e., humic substances) were the
      major chemical oxygen demand (COD) components of aged raw landfill leachate. To
      investigate the behaviours of the large molecular refractory organic compounds
      when they were subjected to oxidation with ozone only (O3 only) and ozone
      combined with hydrogen peroxide (O3/H2O2), the aged raw landfill leachate first
      was filtered with 0.8 and 0.45 microm pore size filters in series, then was
      sequentially fractionated with 10,000 MWCO; 5000 MWCO; and 1000 MWCO membranes,
      and four samples were formed: 0.45 microm-10,000 Da; 10,000-5000 Da; 5000-1000
      Da; and < 1000 Da. Mass distribution profiles of COD, 5-day biochemical oxygen
      demand (BOD5), colour and metals in the aged raw leachate were developed through
      mass balance. After membrane fractionation of the aged raw leachate, the metals
      were fractionated with the humic substances. Each fractionated sample as well as
      the aged raw leachate was oxidised with O3 only and O3/H2O2. The H2O2 enhanced
      the reduction of COD and colour; while, the BOD5 after O3 only was always higher
      than that of O3/H2O2. The addition of H2O2 improved the peak reduction of large
      molecules, but the effects of H2O2 on the fractions of 10,000-5000 Da and 5000
      1000 Da were likely insignificant, which is in accordance with the COD results.
      No correlation was found between the BOD5 increase and the area of new peak
      formed after oxidation. However, the BOD5 of each sample after oxidation with O3
      only was the logarithmic function of its total peak area.

PMID- 16443256
TI  - A canopy layer model and its application to Rome.
AB  - An urban canopy layer model based on four energy balance equations at ground
      level and at building level was developed to simulate and describe the urban
      climate and the heat storage in an urban setting. Thermal and radiative
      characteristics of urban and rural surfaces as well as atmospheric parameters
      related to the general synoptic conditions were used as data input. In addition,
      buildings were modelled as parallelepipeds and the hysteresis of materials was
      taken into account. The model provides as output skin temperature of buildings,
      air temperature and humidity within the canopy layer and hence the mean surface
      temperature and the air temperature at 2 m above surface. The latter parameter
      was used for the comparison with in situ temperature observations. The model was
      applied to Rome in radiative summer and winter episodes. The results, which agree
      with observations, show that the Urban Heat Island (UHI) is a nocturnal
      phenomenon, present both in winter (the greatest difference between urban and
      rural temperatures is about 2 degrees C) and summer (the temperature difference
      is about 5 degrees C), mainly resulting from the urban geometry and the thermal
      properties of materials. The anthropogenic heat does not play an important role
      in the UHI development. A monthly nocturnal behaviour of temperature differences
      between urban and surrounding rural areas shows that the maximum mean value of
      4.2 degrees C occurs in August. Moreover, the parks in the city centre, where
      temperatures are lower, define two distinct heat islands, east and west.

PMID- 16443258
TI  - Characterization of osteoblasts derived from bone marrow stromal cells in a
      modified cell culture system.
AB  - Bone marrow is a complex tissue composed of hematopoietic and stromal stem cells
      with the potential to differentiate into adipogenic, fibroblastic, reticular,
      osteogenic and chondrogenic lineages. Identification of differentiation markers
      during transformation of stromal cells into osteoblasts in a time-dependent
      manner may be informative for cell-based tissue engineering. Therefore, we
      investigated the effects of osteogenic medium (OM) on the proliferation and
      differentiation of rat bone marrow stromal cells (BMSCs). BMSCs from adult male
      rat tibia and femur were collected and cultured in alpha-MEM medium with 10%
      fetal bovine serum, penicillin, streptomycin and gentamycin. After three days of
      culture, the medium covering the adherent cells in culture was changed to OM
      containing dexamethasone, Na-beta-glycerophosphate and ascorbic acid. As a
      control, cell culture was also continued in the original medium for the same time
      period. Differentiated osteoblast cells were collected after 7, 10, 14, 21 and 30
      days of culture, fixed with 4% paraformaldehyde and their immunolabelling for
      osteoblast markers osteonectin (ON) and osteocalcin (OC) was assessed using an
      indirect immunoperoxidase technique. Immunolabelling of ON and OC was detectable
      from day 10 of culture, began to increase on day 14, and increased steadily
      through to day 21. Labelling was highest on day 30 and was more intense in cells
      cultured with OM compared to the culture without OM. The control cells cultured
      in the absence of OM produced negligible levels of both markers. In conclusion,
      our culture system facilitated differentiation of BMSCs into osteoblasts
      featuring osteoblast markers, and these cells may be useful in autologous bone
      implant for the treatment of bone wound healing.

PMID- 16443257
TI  - Quality of anticoagulation with unfractionated heparin plus phenprocoumon for the
      prevention of thromboembolic complications in cardioversion for non-valvular
      atrial fibrillation. Sub-analysis from the Anticoagulation in Cardioversion using
      Enoxaparin (ACE) trial.
AB  - INTRODUCTION: Anticoagulation in cardioversion for atrial fibrillation is
      performed using unfractionated heparin and oral anticoagulants. TEE-guided
      cardioversion, after achievement of therapeutic anticoagulation (1-3 days), may
      be an alternative to the traditional procedure (3-week anticoagulation followed
      by cardioversion). The quality of anticoagulation in atrial fibrillation has not
      been investigated in a randomised trial with TEE-guided cardioversion. We
      analysed respective data from the ACE trial on the quality of conventional
      anticoagulation, where most participating centres chose the TEE-guided approach.
      MATERIALS AND METHODS: In a randomised, prospective, multicentre trial, we
      analysed the efficacy of unfractionated heparin plus phenprocoumon in 248
      patients on an intention-to-treat basis. There were 2373 evaluable
      anticoagulation measurements (out of 2925 measurements) and 4 categories of
      anticoagulation quality (under-, target, over- and severe over-anticoagulation).
      Of patients with evaluable measurements, 88% received short-term anticoagulation
      (4 weeks) in TEE-guided cardioversion. RESULTS: The median time to achieve
      therapeutic anticoagulation (aPTT> or =60 and <80 s or INR> or =2 and <3) was 3
      days. Anticoagulation values were out of therapeutic range in 69.5% of
      measurements during 4- or 7-week follow-up, and never within therapeutic range in
      10% of patients. Of the 15 primary endpoints observed (death, thromboembolism and
      major bleeding complications), only 3 were in patients with anticoagulation
      measurements within therapeutic range. CONCLUSIONS: In this study setting, with
      predominance of 4 weeks anticoagulation in TEE-guided cardioversion for atrial
      fibrillation, therapeutic anticoagulation was reached within 3 days using
      conventional anticoagulation. Despite careful dose adjustments, anticoagulation
      was out of therapeutic range in almost 70% of total measurements and 80% of
      primary endpoints.

PMID- 16443259
TI  - Combined PEG liposomal doxorubicin and gemcitabine are active and have acceptable
      toxicity in patients with platinum-refractory and -resistant ovarian cancer after
      previous platinum-taxane therapy: a phase II Austrian AGO study.
AB  - OBJECTIVES: Platinum resistance is a significant problem in patients with ovarian
      cancer. The aim of this phase II study was to define the response rates, the
      progression-free survival and the toxicity profile of the combination of PEG
      liposomal doxorubicin (L-DXR) and gemcitabine (GEM). MATERIAL AND METHODS: Thirty
      one patients with histologically confirmed platinum-refractory or -resistant
      epithelial ovarian cancer were scheduled to receive 6 cycles of L-DXR 30 mg/m(2)
      on day 1 as well as GEM 650 mg/m(2) on days 1 and 8 every 28 days. RESULTS: The
      median number of chemotherapy cycles given was 4. The mean dose intensity for L
      DXR and GEM on day 1 was 96% and 97%, respectively. The mean dose intensity for
      GEM on day 8 was 93%. The overall response rate was 33% (10 of 30 evaluable
      patients; 20% complete responses). The median progression-free survival was 3.8
      months, and the median overall survival was 15.8 months, respectively. Toxicity
      was acceptable. One quarter of patients developed grade 3 or 4 neutropenia, but
      none developed febrile neutropenia. Palmoplantar erythrodysesthesia (PPE) grades
      2 and 3 occurred in 13% and 3% only, respectively, and no grade 4 PPE was
      observed. Grades 1 to 3 stomatitis was found in 58% of patients (10% grade 3).
      CONCLUSION: The combination of L-DXR and GEM is an active and acceptably
      tolerated option in the treatment of patients with platinum-resistant and 
      refractory ovarian cancer. Dose reductions seem advisable in the case of > or
      =grade 2 stomatitis and/or PPE > or =grade 2.

PMID- 16443260
TI  - Malignant acanthosis nigricans, tripe palms and the sign of Leser-Tre'lat, a hint
      to the diagnosis of early stage ovarian cancer: a case report and review of the
      literature.
AB  - BACKGROUND: Malignant acanthosis nigricans is a mucocutaneous eruption associated
      with internal malignancies. Tripe palms refers to a characteristic velvety
      thickening of the palms, with exaggeration of normal skin markings. The sign of
      Leser-Tre'lat is the presence of multiple seborrheic keratoses and scattered skin
      tags caused by a malignancy. We are reporting the first case of ovarian cancer in
      association with three coexisting cutaneous paraneoplastic dermatosis. CASE: A 52
      year-old female presented with skin manifestation consistent with MAN, TP and the
      sign of Leser-Tre'lat. Patient underwent extensive work up and was discovered to
      have stage I, high grade adenocarcinoma of the ovary. Skin manifestations
      gradually recovered after initiation of chemotherapy. CONCLUSION: The presence of
      acanthosis nigricans in conjunction with tripe palms and the sign of Leser
      Tre'lat are highly suggestive of an internal malignancy and necessitate an
      extensive investigation in order to discover the underlying malignancy.

PMID- 16443261
TI  - Effects of a combined treatment with mTOR inhibitor RAD001 and tamoxifen in vitro
      on growth and apoptosis of human cancer cells.
AB  - OBJECTIVE: Interactions between estrogen receptor signaling and the PI3K/Akt
      pathway are present in estrogen-dependent cancer cells. Therapeutical inhibition
      of each of these pathways has been proven to exert antitumoral effects.
      Inhibition of mammalian target of rapamycin (mTOR), a downstream target of Akt,
      is able to restore tamoxifen response in tamoxifen-resistant breast cancer cells.
      Given that Akt and mTOR phosphorylation also is frequently detected in ovarian
      and endometrial cancer, we intended to find out to what extent mTOR inhibitor
      RAD001 (everolimus) and tamoxifen add to each other's effects on growth and
      apoptosis of cancer cell lines derived from these tissues when given
      concomitantly. METHODS: OVCAR-3 and SK-OV-3 ovarian cancer cells, HEC-1A
      endometrial adenocarcinoma cells and MCF-7 breast cancer cells were treated with
      different concentrations of mTOR inhibitor RAD001 alone or in combination with 4
      OH tamoxifen. Relative numbers of viable cells were assessed by means of the
      resazurin-based Cell Titer Blue assay, cellular apoptosis was examined by
      measurement of activated caspases 3 and 7 by means of the luminometric Caspase
      Glo assay. RESULTS: Treatment with RAD001 resulted in growth inhibition of all
      employed cancer cell lines in a dose-dependent manner, and SK-OV-3 ovarian cancer
      cells proved to be most sensitive to this drug. Moreover, we report the
      observation of additive, but not synergistical growth inhibitory effects of a
      combination treatment with RAD001 and 4-OH TAM on SK-OV-3 and OVCAR-3 ovarian
      cancer cells and MCF-7 breast cancer cells in vitro, whereas no such effect was
      observed in HEC-1A endometrial adenocarcinoma cells. Combination treatment with
      both drugs was demonstrated to be superior to single treatment with lower
      concentrations (0.1 and 1 nM) of RAD001 or standard concentrations of 4-OH TAM.
      Furthermore, RAD001 increased the apoptotic effect triggered by high 4-OH TAM
      concentrations in SK-OV-3 ovarian cancer cells. CONCLUSION: Combination treatment
      with RAD001 and 4-OH TAM in vitro exerts an additive antitumoral effect on
      ovarian cancer cells and MCF-7 breast cancer cells. The significance of these
      data in the clinical situation has to be evaluated in further studies.

PMID- 16443263
TI  - Behavioural and hypothalamic molecular effects of the anti-cancer agent cisplatin
      in the rat: A model of chemotherapy-related malaise?
AB  - Many cancer patients receiving chemotherapy experience fatigue, disturbed
      circadian rhythms, anorexia and a variety of dyspeptic symptoms including nausea.
      There is no animal model for this 'chemotherapy-related malaise' so we
      investigated the behavioural and molecular effects of a potent chemotherapeutic
      agent, cisplatin (CP, 6 mg/kg, i.p.) in rats. Dark-phase horizontal locomotor
      activity declined post-CP reaching a nadir on day 3 (P < 0.001), before
      recovering after 7 days. CP's effect was most marked in the late part (05.00
      07.00) of the dark-phase. Food intake reached a nadir (P > 0.001) at 2 days,
      coincident with an increase in gastric contents (cisplatin 9.04+/-0.8 vs. saline
      2.32+/-0.3 g; P < 0.001). No changes occurred in hypothalamic mRNA expression for
      AGRP, NPY, HCRT, CRH, IL-1, IL-6, TNFalpha, ABCG1, SLC6A4, PPIA and HPRT mRNA but
      tryptophan hydroxylase (TPH) mRNA was decreased (47%, P < 0.05) at day 21 post
      CP. This shows that despite marked behavioural effects of cisplatin, only a
      discrete change (TPH) was found in hypothalamic mRNA expression and that occurred
      when the animals' behaviour had recovered. Findings are discussed in relation to
      the neuropharmacology of chemotherapy-induced malaise.

PMID- 16443262
TI  - Maspin expression and localization impact on angiogenesis and prognosis in
      ovarian cancer.
AB  - INTRODUCTION: The goal of this study is to evaluate the relation of maspin
      expression and its cellular localization to markers of angiogenesis in epithelial
      ovarian serous carcinoma (OSC). MATERIALS AND METHODS: We identified 118 patients
      with high-grade advanced stage OSC who were treated at our institution. Clinical
      data were collected, and immunohistochemistry (IHC) with antibodies to VEGF,
      CD34, COX-2, and maspin was performed on paraffin-embedded tumor blocks. CD34
      immunostaining was used to determine microvessel density. The correlation between
      the various molecular markers was assessed using the Chi-square test. Survival
      analysis was computed using the Kaplan-Meier model, and various prognostic
      variables were compared using Cox regression analysis. RESULTS: Maspin expression
      was noted in 81.4% (96/118) of tumors. Expression was localized to the nuclear
      compartment in 21.2% of cases, whereas 60.2% of cases showed evidence of
      cytoplasmic +/- nuclear expression. Tumors that exhibited nuclear maspin
      expression had lower VEGF and COX-2 expression than tumors with negative or
      cytoplasmic expression. Tumors with high nuclear maspin expression had lower mean
      MVD than those with low or negative expression. The median survival based on
      localization of maspin was 1146 days for those with negative tumors, 1803 days
      for those with nuclear maspin, and 637 days for those with cytoplasmic maspin (P
      < 0.001). In a Cox regression analysis, maspin localization was an independent
      prognostic factor. CONCLUSION: Maspin expression and localization seem to play a
      role in ovarian cancer angiogenesis and progression. High nuclear expression was
      associated with reduced markers of angiogenesis and prolonged survival.

PMID- 16443265
TI  - Contraction stress and bond strength to dentinfor compatible and incompatible
      combinations of bonding systems and chemical and light-cured core build-up resin
      composites.
AB  - OBJECTIVE: Recent studies have shown that adhesives containing acidic monomers
      combined with composites can adversely effect the polymerization reaction
      producing low bond strengths. This phenomenon may also occur in making composite
      build-ups, jeopardizing one of the key factors for a successful core build-up
      restoration. The aim of this study was to investigate the contraction stress
      development and bond strength to dentin of core build-up resin composites
      combined with adhesives of various acidities. In addition the hypothesis tested
      was that light irradiation through chemical-cured composites during curing does
      not influence contraction stress or bond strength to dentin. METHODS: The
      chemical-cured (Clearfil Core) and light-cured (Clearfil Photo Core) core build
      up resin composites were combined with two light-cured adhesives, Clearfil SE
      Bond (pH=1.8) and One-Step Bond (pH=4.3) and two dual-cured adhesives, Clearfil
      Photo Bond (pH=2.5) and All-Bond 2 (pH=6.1). Contraction stress development (at
      C=3) was determined for a period of 30 min in a universal testing machine where
      the opposing bonding surfaces were glass and dentin. After the 30 min period, the
      specimens were loaded in tension to determine the bond strength to dentin. To
      test the hypothesis, the combinations of the chemical-cured composites with the
      four bonding systems were also light irradiated for 40s right at the start of
      curing. RESULTS: For all composite-adhesive combinations tested, the adhesion to
      dentin resisted the developing polymerization contraction stresses. Both, dentin
      as a substrate to bond at and the use of adhesives, were showed to play an
      important role in keeping the contraction stresses low. The chemical-cured
      composite (Clearfil Core) combined with the light-cured adhesive SE Bond (pH=1.8)
      showed for both contraction stress and bond strength significant lower values
      than the other combinations. The hypothesis was accepted for combinations of the
      chemical-cured composite with All-Bond 2 and One-Step Bond, but was not supported
      by combinations with Clearfil SE Bond or Clearfil Photo Bond, as a significant
      increase in contraction stress was found. The higher values found for bond
      strength were not significant. SIGNIFICANCE: Besides combinations of chemical
      cured core build-up composites with light or dual-cured adhesives as recommended
      by the manufacturer, also combinations with adhesives of other manufacturers are
      compatible, provided that the pH is higher than approximately 4.3. Chemical-cured
      core build-up composites combined with light-cured adhesives with a pH as low as
      1.8 lead to a significantly lower stress and bond strength compared to other
      combinations. Light irradiation during curing through a combination of a chemical
      cured composite and a low pH adhesive reactivates polymerization.

PMID- 16443264
TI  - Smoking and SF-36 health functioning.
AB  - OBJECTIVE: To examine the association between smoking and general health as
      measured by the Short-Form Health Survey (SF-36) questionnaire. METHODS: Data
      derived are from three cross-sectional surveys conducted in 2000, 2001 and 2002.
      Respondents to the postal surveys were middle-aged employees of the City of
      Helsinki (1799 men and 7171 women, response rate 67%). Smoking status was divided
      into current heavy and moderate smokers, ex-smokers and never smokers. Health
      status was measured by the eight SF-36 subscales and the physical and mental
      component summaries. RESULTS: On the physical subscales, current smokers reported
      poorer health than non-smokers on general health and physical functioning in men.
      On the mental subscales, current smokers had consistently poorer health than non
      smokers. However, often only heavy smokers differed from non-smokers. No
      differences were found between ex-smokers and never smokers on any subscale or
      the component summaries of the SF-36. CONCLUSIONS: Differences between smoking
      categories were found on some physical and all mental subscales of the SF-36. The
      differences were slightly larger among men. As heavy smokers more often report
      limitations with daily activities as well as loss of well-being, these
      impairments potentially provide valuable incentives for non-smoking to be used in
      health education messages and interventions.

PMID- 16443266
TI  - Degradation of porphyran from Porphyra haitanensis and the antioxidant activities
      of the degraded porphyrans with different molecular weight.
AB  - In the present paper, ascorbate and hydrogen peroxide (H2O2) were used to degrade
      porphyran. It was found that porphyran could be degraded by free radical that was
      generated by ascorbate and H2O2 in combination. It was possible to prepare
      desired porphyran products with different molecular weight by adjusting ascorbate
      to H2O2 proportions and their concentrations. The molar ratio of 1 was
      demonstrated more effective than in other ratios. Higher concentrations
      accelerated the degradation. Moreover, results of chemical analysis and FT-IR
      spectra suggested that the main structure of degraded products still remained
      although some changes happened. The degraded and natural porphyrans possessed
      scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical activity and reducing
      power. Higher antioxidant activities were found in both systems when the
      molecular weight was reduced. The results indicated that the antioxidant
      activities were closely related to the molecular weight. The degraded porphyrans
      are potential antioxidant in vitro.

PMID- 16443267
TI  - Some physical and microstructural properties of genipin-crosslinked gelatin
      maltodextrin hydrogels.
AB  - The physical properties and microstructure of gelatin-maltodextrin hydrogels
      fixed with genipin (GP) were investigated as a function of pH (3-7), maltodextrin
      (MD) (0-9%, w/w) and GP (0-10 mM levels), at a constant gelatin (G) concentration
      (10%, w/w). Network strength (elastic modulus, E) and swelling behavior were
      characterized by large deformation testing and by swelling index (SI). In
      general, network strength increased and swelling decreased at higher pH, MD and
      GP levels, except at pH 3, where E was independent of the GP concentration until
      approximately 7.5 mM, above which it declined. Confocal scanning laser microscopy
      (CLSM) images showed phase separation to be suppressed at pH 3, whereas at pH 7,
      separation into a self-similar dispersed phase was apparent. Overall, the
      judicious use of GP to crosslink G was an appropriate means of kinetically
      trapping MD within the gelatin network.

PMID- 16443268
TI  - Osteoprogenitor response to semi-ordered and random nanotopographies.
AB  - In bone tissue engineering, it is desirable to use materials to control the
      differentiation of mesenchymal stem cell populations in order to gain direct bone
      apposition to implant materials. It has been known for a number of years that
      microtopography can alter cell adhesion, proliferation and gene expression. More
      recently, the literature reveals that nanotopography is also of importance. Here,
      the reaction of primary human osteoprogenitor cell populations to
      nanotopographies down to 10 nm in size is considered. The topographies were
      originally produced by colloidal lithography and polymer demixing on silicon and
      then embossed (through an intermediate nickel shim) into polymethylmethacrylate.
      The biological testing considered cell morphology (image analysis of cell
      spreading and scanning electron microscopy), cell cytoskleton and adhesion
      formation (fluorescent staining of actin, tubulin, vimentin and vinculin) and
      then subsequent cell growth and differentiation (fluorescent staining of
      osteocalcin and osteopontin). The results demonstrated that the nanotopographies
      stimulated the osteoprogenitor cell differentiation towards an osteoblastic
      phenotype.

PMID- 16443269
TI  - The effect of the amelogenin fraction of enamel matrix proteins on fibroblast
      mediated collagen matrix reorganization.
AB  - Enamel matrix proteins (EMP), extracted from developing porcine teeth, promote
      not only periodontal regeneration but also cutaneous wound healing presumably via
      the amelogenin fraction. Because it is unclear whether the effect of EMP can be
      ascribed to amelogenins, we compared EMP with recombinant amelogenin in the
      relaxed dermal equivalent (DE) in vitro model for early wound contraction. EMP
      and recombinant porcine amelogenin (rP172) at 1 mg/ml were incorporated into DEs
      composed of human dermal fibroblasts and a type I collagen matrix. The area
      reduction, as a measure of contraction, as well as fibroblast numbers and TGF
      beta1 levels, were quantified over 7 days in culture in the presence of 10%
      foetal bovine serum. Both EMP and recombinant amelogenin increased contraction (p
      < 0.005) and fibroblast numbers (p < 0.005) compared with controls (acetic acid
      vehicle and 1mg/ml porcine serum albumin) and the positive control TGF-beta1
      added at 10 ng/ml. Increased contraction with EMP and recombinant amelogenin was
      most pronounced after the first day of incubation and was associated with
      elevated (p < 0.005) TGF-beta1 levels in conditioned medium. In conclusion, the
      amelogenin component of EMP augmented fibroblast-driven collagen matrix
      remodelling, at least partially, by increasing the endogenous production of TGF
      beta1. These effects of EMP/amelogenin may be beneficial for cutaneous wound
      healing.

PMID- 16443270
TI  - Sustained release of dexamethasone from hydrophilic matrices using PLGA
      nanoparticles for neural drug delivery.
AB  - The release of the anti-inflammatory agent dexamethasone (DEX) from nanoparticles
      of poly(lactic-co-glycolic acid) (PLGA) embedded in alginate hydrogel (HG)
      matrices was investigated. DEX-loaded PLGA nanoparticles were prepared using a
      solvent evaporation technique and were characterized for size, drug loading, and
      in-vitro release. The crosslinking density of the HG was studied and correlated
      with drug release kinetics. The amount of DEX loaded in the nanoparticles was
      estimated as approximately 13 wt%. The typical particle size ranged from 400 to
      600 nm. The in-vitro release of DEX from NPs entrapped in the HG showed that 90%
      of the drug was released over 2 weeks. The impedance of the NP-loaded HG coatings
      on microfabricated neural probes was measured and found to be similar to the
      unmodified and uncoated probes. The in-vivo impedance of chronically implanted
      electrodes loaded with DEX was maintained at its initial level, while that of the
      control electrode increased by 3 times after about 2 weeks after implantation
      until it stabilized at approximately 3 MOmega. This improvement in performance is
      presumably due to the reduced amount of glial inflammation in the immediate
      vicinity of the DEX-modified neural probe.

PMID- 16443271
TI  - Effect of 3-hydroxyhexanoate content in poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) on in vitro growth and differentiation of smooth muscle cells.
AB  - In this paper, comprehensive characteristics including cell attachment, cell
      proliferation status, cell cycle progression and phenotypic changes of smooth
      muscle cells from rabbit aorta (RaSMCs) were studied on poly(3-hydroxybutyrate-co
      3-hydroxyhexanoate) (PHBHHx) containing 0-20% HHx (mol%) in comparison with
      tissue culture plates (TCPs). Results demonstrated that RaSMCs adhered better on
      PHBHHx containing 12% HHx (12%HHx) although they proliferated better on 20%HHx
      containing PHBHHx films (20%HHx). This was explained by the difference in cell
      cycle progression observed using flow cytometry, as it was found that only 20%HHx
      containing polymer could maintain the normal cell cycle evolution as TCPs did
      after 3 d incubation. The highest expression level and typical spindle-like
      distribution of alpha-actin on 20%HHx-containing polymer were characterized as
      the contractile-like phenotype, suggesting that RaSMCs tended to differentiate
      rather than proliferate compared to the cells grown on 12%HHx polymer. Results
      obtained above suggested that 20%HHx was suitable for RaSMCs proliferation,
      leading to its change to contractile phenotype. This study extends the potential
      applications of PHBHHx in SMCs-related graft scaffold fabrication for tissue
      engineering.

PMID- 16443272
TI  - Are myelodysplastic syndromes "cancer"? Unexpected adverse consequences of
      linguistic ambiguity.
AB  - Myelodysplastic syndromes (MDS) are clonal, neoplastic disorders of hematopoietic
      tissue that convey a guarded prognosis, but physicians vary in whether they refer
      to MDS as a "cancer" when discussing the diagnosis with patients. Because of past
      ambiguity about whether MDS is truly a malignancy, confusion about MDS
      terminology is widespread. Additionally, patients who carry one of the dubious
      cancer-specific health insurance policies are usually not eligible for financial
      benefits when they receive a diagnosis of MDS. Likewise, patients with MDS who
      have been led to believe they do not have a form of cancer by their primary
      physician may become upset when seeing another health care provider who does
      refer to MDS in this way. Here, I discuss evidence supporting broader
      consideration of MDS as a form of malignant neoplasia - i.e., cancer - as well as
      some of the relevant practical issues.

PMID- 16443273
TI  - Comparative analyses of two cryptic plasmids from Haemophilus somnus (Histophilus
      somni).
AB  - Haemophilus somnus is an opportunistic bacterial pathogen capable of causing
      pneumonia, septicemia, and other systemic infections in bovines. An H. somnus
      isolate from bovine abortion (strain 649) was found to carry a approximately 1.3
      kb plasmid (pHS649) that contained partial homology to two previously sequenced
      Haemophilus/Histophilus plasmids by BLAST analyses. Sequence analysis of pHS649
      identified a putative RepA protein with 48% similarity to the RepA protein of
      Escherichia coli plasmid pKL1. A approximately 5 kb plasmid (pHS129) from H.
      somnus preputial isolate 129Pt was also sequenced and found to encode two copies
      of a putative RepB protein. Whereas pHS649 stably replicated in E. coli DH5alpha,
      pHS129 did not. Genetic relatedness and possible replication mechanisms of these
      plasmids are described.

PMID- 16443274
TI  - Modeling human exposures to air pollution control (APC) residues released from
      landfills in England and Wales.
AB  - Human exposures to air pollution control (APC) residues released from 6 landfills
      were modeled and assessed. Following a qualitative risk characterisation, direct
      and indirect exposures were quantified. Site-specific air dispersion modeling was
      conducted for PM(10), PCDDs/PCDFs, Pb, Cd, As and Cr(VI) concentrations at the
      closest residential points of exposure for 4 landfill sites accepting, in total,
      75% w/w of the APC residues disposed of in 2000-2001 (UK). Inhalation risks,
      assessed by reference to air quality standards at residential exposure points,
      were assessed as insignificant. Preliminary modeling suggested that indirect
      exposures from PCDDs/PCDFs at the 95th percentile level for the site where APC
      deposition rates were highest could potentially exceed the tolerable daily soil
      intake (TDSI) but this warrants further study given the model limitations. These
      results offer an initial screen of the significance of potential risks from APC
      disposal, which is of value in addressing concerns about the uncertainty of
      potential risks to human health from bulk APC disposal at strategic locations.

PMID- 16443275
TI  - AIDS-related cerebral toxoplasmosis with hyperintense foci on T1-weighted MR
      images: a case report.
AB  - The neuroradiological findings are helpful for the diagnosis of toxoplasmic
      encephalitis. The T1 hypersignal intensity foci on brain magnetic resonance (MR)
      images without contrast enhancement are presented and can be a pathognomonic sign
      of this disease.

PMID- 16443276
TI  - The serological diagnosis of staphylococcal infective endocarditis.
AB  - OBJECTIVES: Establishing the diagnosis of infective endocarditis (IE) can be
      difficult when blood cultures remain sterile or echocardiography is inconclusive.
      Staphylococcus aureus is a common aetiological microorganism in IE and is
      associated with severe valvular destruction and increased mortality. Early
      diagnosis using culture and antibiotic independent tests would be preferable to
      allow prompt antibiotic administration. We have developed and evaluated 2
      serological assays for the rapid identification of a staphylococcal aetiology in
      infective endocarditis. The assays measure IgG against whole cells of S. aureus
      and IgG against lipid S, a novel extracellular antigen released by Gram-positive
      microorganisms. METHODS: Serum was collected from 130 patients with IE and 94
      control patients. IgG against whole cells of S. aureus and against lipid S was
      measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Anti-lipid S IgG
      titres were higher in IE caused by Gram-positive microorganisms than in controls
      (p<0.0001) and higher in staphylococcal IE than in both controls and IE caused by
      other microorganisms (p=0.0003). Anti-whole cell staphylococcal IgG was
      significantly higher in serum from patients with staphylococcal IE than in IE
      caused by other microorganisms and control samples (p<0.0001). CONCLUSION: High
      anti-whole cell IgG titres are predictive of a staphylococcal aetiology in IE.
      Elevated serum anti-lipid S IgG titres are predictive of Gram-positive infection
      compared to controls, very high titres being associated with staphylococcal IE.

PMID- 16443277
TI  - Pharmacology of erectile dysfunction in man.
AB  - Erectile dysfunction (ED) is defined as the consistent or recurrent inability of
      a man to attain and/or maintain a penile erection sufficient for sexual activity
      (2nd International Consultation on Sexual Dysfunction-Paris, June 28th-July 1st,
      2003). Following the discovery and introduction of sildenafil, research on the
      mechanisms underlying penile erection has had an enormous boost and many
      preclinical and clinical papers have been published in the last 5 years. This
      review is structured in order to give the reader an overview of the clinical and
      preclinical data available on the peripheral regulation of and the mediators
      involved in human penile erection. The most widely accepted risk factors for ED
      are discussed. The article is focused on human data, and the safety and
      effectiveness of the 3 commercially available Phosphodiesterase-5 (PDE5)
      inhibitors used to treat ED are also discussed.

PMID- 16443278
TI  - Complement and demyelinating disease: no MAC needed?
AB  - It has long been accepted that the complement system participates in the onset,
      evolution, and exacerbation of demyelinating disease, and it is widely suspected
      that this is accomplished mainly via destruction of nervous tissue by membrane
      attack complex (MAC)-mediated lysis of oligodendrocytes and neurons. However,
      recent studies using mutant mice indicate the MAC may not be so important. For
      example, mice lacking C5 and mice lacking the C5a receptor both develop
      experimental autoimmune encephalomyelitis (EAE) with the same frequency and
      intensity as their wild type counterparts. Also, transgenic mice that express C5a
      exclusively in the central nervous system (CNS) develop EAE that is not
      remarkably different from that in non-transgenic littermates. Since C5 is
      required for formation of the MAC, development of fulminant EAE in the absence of
      this complement protein demonstrates that non-complement-mediated mechanisms of
      CNS damage are operating. Paradoxically, mice lacking C3, mice lacking the C3a
      receptor, and mice lacking the complement receptor type 3 develop attenuated EAE,
      while mice that express C3a exclusively in the CNS develop severe and often
      fulminant EAE. Based on these newer data, we posit that C3-derived biologically
      active fragments, rather than C5 and the MAC, are central players in the
      pathophysiology of complement in EAE.

PMID- 16443279
TI  - Stiffness of normal and pathological erythrocytes studied by means of atomic
      force microscopy.
AB  - During recent years, atomic force microscopy has become a powerful technique for
      studying the mechanical properties (such as stiffness, viscoelasticity, hardness
      and adhesion) of various biological materials. The unique combination of high
      resolution imaging and operation in physiological environment made it useful in
      investigations of cell properties. In this work, the microscope was applied to
      measure the stiffness of human red blood cells (erythrocytes). Erythrocytes were
      attached to the poly-L-lysine-coated glass surface by fixation using 0.5%
      glutaraldehyde for 1 min. Different erythrocyte samples were studied:
      erythrocytes from patients with hemolytic anemias such as hereditary
      spherocytosis and glucose-6-phosphate-dehydrogenase deficiency patients with
      thalassemia, and patients with anisocytosis of various causes. The determined
      Young's modulus was compared with that obtained from measurements of erythrocytes
      from healthy subjects. The results showed that the Young's modulus of
      pathological erythrocytes was higher than in normal cells. Observed differences
      indicate possible changes in the organization of cell cytoskeleton associated
      with various diseases.

PMID- 16443280
TI  - Association between serotonergic candidate genes and specific phenotypes of
      obsessive compulsive disorder.
AB  - BACKGROUND: The successful use of serotonin reuptake inhibitors (SRIs) in
      obsessive-compulsive disorder (OCD) has led to the hypothesis that serotonin
      plays a pivotal role in the pathogenesis of OCD. The purpose of the present study
      was to investigate the role of the serotonin transporter (5-HTT) and serotonin 5
      HT1B and 5-HT2A receptor genes in OCD. METHOD: The distribution of polymorphic
      variants was analyzed in 156 OCD cases and 134 control individuals by means of
      case-control association studies. Potential relevant OCD phenotypes founded on
      age of onset, positive family history for OCD, clinical subtypes, comorbidity and
      symptom severity were stratified according to 5-HTT, 5-HT1B and 5-HT2A genotypes.
      RESULTS: Patients did not show significant differences in genotype distribution
      and allele frequency for polymorphisms investigated relative to controls.
      However, taking in account OCD phenotypes, we found indication towards an
      association of the 5-HTTLPR S-allele with female OCD patients, and the 5-HT2A G
      allele and GG genotype with patients with a positive family history of OCD and an
      early onset of disease. CONCLUSIONS: Our data yields interesting preliminary
      results as regards the genetic underpinnings of OCD phenotypes that warrant
      further discussion and investigation.

PMID- 16443281
TI  - Dispositional optimism and the risk of depressive symptoms during 15 years of
      follow-up: the Zutphen Elderly Study.
AB  - OBJECTIVE: It is unclear whether the personality trait of dispositional optimism,
      defined in terms of generalized positive outcome expectancies, life engagement,
      and a future orientation, has a protective effect on the development of
      depression in community-dwelling elderly men. METHODS: We included 464 men aged
      64 to 84 years (mean 70.8; SD 4.6) with complete data at baseline and at 5 years
      of follow-up in a prospective cohort study with a follow-up period of 15 years.
      In 1985, 1990, 1995 and 2000 dispositional optimism was assessed using a 4-item
      questionnaire, and in 1990, 1995 and 2000 depressive symptoms were assessed by
      the Zung self-rating depression scale (SDS). Logistic regression was used to
      estimate odds ratios for the development of depressive symptoms (i.e., Zung SDS >
      or = 50). RESULTS: The cumulative incidence for depressive symptoms was 44% (n =
      202) after 15 years follow-up. Dispositional optimism predicted for a lower
      cumulative incidence of depressive symptoms with an odds ratio of 0.23 (95%
      confidence interval 0.15-0.36; high vs. low optimism). The protective effect
      remained unaffected after multivariate adjustment for age, self-rated health,
      cardiovascular disease, education, and physical activity. In men free of
      depressive symptoms in 1990, the protective effect of dispositional optimism
      persisted. LIMITATION: The dispositional optimism scale has not been validated
      against the 'Life Orientation Test'. CONCLUSIONS: Dispositional optimism protects
      against the development of depressive symptoms during 15 years of follow-up in
      elderly community-dwelling men.

PMID- 16443282
TI  - Pathological gambling and mood disorders: clinical associations and treatment
      implications.
AB  - BACKGROUND: The rapidly expanding gambling business has resulted in an increasing
      number of gamblers, and the problem is likely to get worse in the future.
      Traditionally, mood and gambling symptoms have been known to overlap. In the
      present review we attempt to examine the diagnostic associations and implications
      for treatment. METHOD: Selected published papers on the frequencies of mood
      disorders among patients who have gambling disorder or gambling disorder among
      patients who have mood disorder have been reviewed. Recently emerging new
      treatment methods for gambling disorder have been reviewed and a brief summary
      has been added. RESULTS: SCID based study results show a close link between
      gambling and mood disorders. The prevalence of manic disorder reaches to
      approximately one fourth of the pathological gambling disorder population. The
      prevalence of depression is much higher, reaching to over half of the population
      in some studies. LIMITATIONS: The studies included in the present paper involve
      inpatients, outpatients, subjects recruited through advertisements and prison
      populations. Thus the data need to be interpreted as such. Standardized
      assessment instruments are not used in all studies. Methodological issues such as
      primary or secondary nature of depression have not been addressed adequately in
      these studies. The findings, however, offer new insights for the assessment and
      treatment of complicated gambling disorder cases. CONCLUSIONS: A high prevalence
      rate of manic and depressive disorders has been recorded among pathological
      gambling disorder patients. A rational treatment approach to each defined subset
      of complicated gambling disorder is discussed.

PMID- 16443283
TI  - Characteristics of high intent suicide attempters admitted to a general hospital.
AB  - BACKGROUND: Suicide intent is a strong predictor of repetition of attempts and
      subsequent suicide. This study aimed to compare socio-demographics, clinical
      factors and method of attempt in high and low intent suicide attempters. METHOD:
      All patients admitted following attempted suicide to a teaching hospital were
      interviewed. Socio-demographic information, details of the attempt and
      psychiatric diagnosis were recorded. Scales for assessing suicide intent,
      lethality, recent life-events and depression were administered. Comparison
      between high intent and low intent groups were done to identify the
      characteristics of patients who had high suicidal intent. RESULTS: The sample
      comprised 203 patients, 84 of whom were classified as high intent attempters
      using the Suicide Intent Scale. The high intent group were significantly more
      likely to be male (p = 0.01), of single marital status (p = 0.04), have a
      psychiatric diagnosis, especially depression (p = 0.001) and use self immolation
      to attempt suicide (p = 0.001). Patients with high intent had significantly
      higher lethality (p = 0.001) and recent stressful life-event scores (p = 0.001).
      CONCLUSIONS: High intent suicide attempts are associated with distinct socio
      demographic profiles and psychiatric morbidity. Routine assessment of intent may
      help to identify individuals with high risk, who can be offered targeted
      interventions.

PMID- 16443284
TI  - Robin sequence: a retrospective review of 115 patients.
AB  - OBJECTIVES: Review a large series of patients with Robin sequence to document the
      incidence of (1) associated syndromic diagnoses; (2) co-morbid conditions; (3)
      frequency and type of operative management for airway compromise and feeding
      difficulties; and (4) possible differences in treatment between syndromic and
      nonsyndromic infants. METHODS: Retrospective case-review of 115 patients with
      Robin sequence managed between 1962 and 2002 at two tertiary-care teaching
      hospitals for evaluation of demographic information, clinical findings, and
      treatment interventions. RESULTS: Fifty-four percent (N=63) of patients were
      nonsyndromic. Syndromic patients included: Stickler syndrome (18%),
      velocardiofacial syndrome (7%), Treacher-Collins (5%), facial and hemifacial
      microsomia (3%), and other defined (3.5%) and undefined (9%) disorders. There was
      no statistical difference between the syndromic and nonsyndromic patients with
      regard to need for operative airway management (Fisher's exact test, p=0.264).
      Forty-two percent of patients required a feeding gastrostomy tube to correct
      feeding difficulties. Patients with a syndromic diagnosis were more likely to be
      developmentally delayed. Fifty-one (44%) patients underwent operative airway
      management: 61% underwent tongue-lip adhesion and 39% underwent tracheotomy.
      Fifteen percent of patients initially had tongue-lip adhesion subsequently
      required tracheotomy. While the preferred treatment for respiratory compromise
      differed between the two institutions, the percentage of patients requiring
      operative intervention was similar. CONCLUSIONS: The pathogenesis of Robin
      sequence is multifactorial and syndromic in nearly half of the patients.
      Operative treatment of respiratory failure was required in 44% of infants; the
      rate was similar in both hospitals. The operative approach differed significantly
      between the institutions, however, based on the philosophy and training of the
      managing surgical specialty. Co-morbid factors such as baseline cardiopulmonary
      and neurologic status did not play a significant role in surgical decision
      making.

PMID- 16443285
TI  - Meaningful silences: how dopamine listens to the ACh pause.
AB  - Mesostriatal dopaminergic neurons (DANs) and striatal cholinergic neurons
      (tonically active neurons, TANs) participate in signalling the behavioural or
      reward-related significance of stimuli in the environment. An antagonistic
      balance between dopamine (DA) and ACh is well known to regulate postsynaptic
      signal integration in the striatum. Recent findings have revealed additional
      presynaptic ACh-DA interactions of previously unappreciated sophistication.
      Striatal ACh acts presynaptically to polarize powerfully how opposing DAN
      activities are transduced into DA release. Furthermore, characteristic reward
      related activities of TANs and DANs are temporally coincident but differently
      variant with reward probability. Reward-related DA signals could therefore be
      governed by the concomitant activity in TANs. This article discusses the dynamic
      implications for DA signalling when these phenomena act in concert. TAN pauses
      might powerfully enhance the contrast, or salience, of DA signals offered by
      reward-related bursts, and even by reward omission-related pauses, in DANs.
      Through such mechanisms, TAN-DAN interactions would be functionally cooperative.

PMID- 16443286
TI  - Dopamine in neurotoxicity and neuroprotection: what do D2 receptors have to do
      with it?
AB  - Accurate control of dopamine levels and/or the resulting dopamine-receptor
      interaction is essential for brain function. Indeed, several human neurological
      and psychiatric disorders are characterized by dysfunctions of the dopaminergic
      system. Dopamine has been reported to exert either protective or toxic effects on
      neurons, yet it is unclear whether these effects are receptor-dependent and, if
      so, which dopamine receptor could be involved. The D(2) dopamine receptor
      occupies a privileged position because its signalling might be neuroprotective in
      human diseases, such as Parkinson's disease, ischaemia and epilepsy. Unravelling
      the role of D(2) receptors in neuronal death and survival might be central to
      understanding the mechanisms that underlie several neuropathologies.

PMID- 16443287
TI  - Intraneuronal trafficking of G-protein-coupled receptors in vivo.
AB  - In vitro studies have widely demonstrated that the abundance and availability of
      G-protein-coupled receptors (GPCRs) at the cell surface is regulated by the
      neuronal environment and is the result of complex intraneuronal trafficking.
      However, this regulation is still poorly understood in vivo. Modulation of
      receptor availability at the neuronal membrane is a key event in the regulation
      of neuronal functions (e.g. neurotransmitter release or neuronal excitability in
      physiological, pathological or therapeutic conditions). We discuss the effects of
      duration of receptor stimulation (acute versus chronic) on the intraneuronal
      trafficking of GPCRs in vivo, and we show that this trafficking might differ
      according to subcellular compartment (soma, dendrites or axon terminals).

PMID- 16443288
TI  - AMPA signalling in nascent glutamatergic synapses: there and not there!
AB  - Nascent glutamatergic synapses are thought to be equipped with only NMDA
      receptors and to mature in a stepwise fashion when AMPA receptors are acquired
      later, through specific patterns of activity. We review recent data suggesting
      that AMPA receptors are in fact present in the nascent synapse but in a labile
      state. The nascent synapse can easily switch between AMPA-signalling and AMPA
      silent states in a manner not requiring activation of NMDA receptors or
      metabotropic glutamate receptors. NMDA receptor activation by correlated
      presynaptic and postsynaptic activity can switch the nascent synapse to a mature,
      more stable state, in which AMPA receptor signalling is modified only through
      conventional plasticity processes. Thus, the AMPA receptor silence of nascent
      glutamatergic synapses depends on the synaptic activation history rather than on
      the nascent state itself.

PMID- 16443290
TI  - NMDA receptor blockers prevents the facilitatory effects of post-training intra
      dorsal hippocampal NMDA and physostigmine on memory retention of passive
      avoidance learning in rats.
AB  - In the present study, the effects of post-training intra-dorsal hippocampal
      (intra-CA1) injection of an N-methyl-D-aspartate (NMDA) receptor agonist and
      competitive or noncompetitive antagonists, on memory retention of passive
      avoidance learning was measured in the presence and absence of physostigmine in
      rats. Intra-CA1 administration of lower doses of the NMDA receptor agonist NMDA
      (10(-5) and 10(-4) microg/rat) did not affect memory retention, although the
      higher doses of the drug (10(-3), 10(-2) and 10(-1) microg/rat) increased memory
      retention. The greatest response was obtained with 10(-1) microg/rat of the drug.
      The different doses of the competitive NMDA receptor antagonist DL-AP5 (1, 3.2
      and 10 microg/rat) and noncompetitive NMDA receptor antagonist MK-801 (0.5, 1 and
      2 microg/rat) decreased memory retention in rats dose dependently. Both
      competitive and noncompetitive NMDA receptor antagonists reduced the effect of
      NMDA (10(-2) microg/rat). In another series of experiments, intra-CA1 injection
      of physostigmine (2, 3 and 4 microg/rat) improved memory retention. Post-training
      co-administration of lower doses of NMDA (10(-5) and 10(-4) microg/rat) and
      physostigmine (1 microg/rat), doses which were ineffective when given alone,
      significantly improved the retention latency. The competitive and noncompetitive
      NMDA receptor antagonists, DL-AP5 and MK-801, decreased the effect of
      physostigmine (2 microg/rat). Atropine decreased memory retention by itself and
      potentiated the response to DL-AP5 and MK-801. In conclusion, it seems that both
      NMDA and cholinergic systems not only play a part in the modulation of memory in
      the dorsal hippocampus of rats but also have demonstrated a complex interaction
      as well.

PMID- 16443289
TI  - Optical probing of neuronal circuit dynamics: genetically encoded versus
      classical fluorescent sensors.
AB  - During the past few decades, optical methods for imaging activity in networks
      composed of thousands of neurons have been developed. These techniques rely
      mainly on organic-chemistry-based dyes as indicators of Ca(2+) and membrane
      potential. However, recently a new generation of probes, genetically encoded
      fluorescent protein sensors, has emerged for use by physiologists studying the
      operation of neuronal circuits. We critically review the development of these new
      probes, and analyze objectives and experimental conditions in which classical
      probes are likely to prevail and where the fluorescent protein sensors will open
      paths to previously unexplored territories of functional neuroimaging.

PMID- 16443291
TI  - Behaviour changes in a transgenic model of Huntington's disease.
AB  - Huntington's disease is an autosomal dominant inherited disorder, caused by an
      expanded polyglutamine region of a protein called huntingtin with unknown
      function. Transgenic mice expressing the N-terminal of huntingtin, containing 82
      glutamines, exhibit a progressive disorder, which resembles to the human disease.
      In this study, we tested the longitudinal behaviour changes in this transgenic
      line in open-field and elevated-plus-maze tests. The motor performance
      deteriorated at 12 weeks of age and the disease progressed as indicated by the
      decreased total distance covered, the decreased mean velocity and the decreased
      exploratory behaviour. The level of anxiety was unchanged in transgenic mice as
      compared with their littermate controls. The motor deterioration was similar to
      that in other Huntington's disease models, while the level of anxiety was
      different. These tests are suitable means of following the progression of the
      disease and useful for studies of the effects of therapeutic interventions.

PMID- 16443292
TI  - Sex-related lateralized effect of emotional content on declarative memory: an
      event related potential study.
AB  - Several studies suggest that emotional arousal can promote memory storage. In
      this study, we evaluated the effects of emotional content on declarative memory,
      utilizing an adaptation of two versions of the same story, with different
      arousing properties (neutral or emotional), which have been already employed in
      experiments involving the enhancing effects of emotions on memory retention. We
      used event related potentials (ERP) to evaluate whether there is a sex-related
      hemispheric lateralization of electrical potentials elicited by the emotional
      content of a story. We compared left and right hemisphere P300 waves, recorded in
      P3 and P4 electrode sites, in response to emotional or neutral stimuli in men and
      women. In the left hemisphere, emotional stimuli elicited a stronger P300 in
      women, compared to men, as indexed by both amplitude and latency measures;
      moreover, the emotional content of the story elicited a stronger P300 in the
      right hemisphere in men than in women. The better memory for the arousal material
      may be related to the differential P300 at encoding. These data indicate that
      both sex and cerebral hemisphere constitute important, interacting influences on
      neural correlates of emotion, and of emotionally influenced memory.

PMID- 16443293
TI  - AT1 receptor antagonism ameliorates acute pancreatitis-associated pulmonary
      injury.
AB  - Acute pancreatitis (AP) is an inflammatory disease characterized by tissue edema,
      necrosis and hemorrhage. The mortality rate associated with this disease is
      particularly high when the inflammation has become systemic. Recently, activation
      of the pancreatic renin-angiotensin system (RAS) was shown to play a role in AP.
      The present study investigated whether administering an AT1 receptor antagonist
      decreases the severity of AP and pancreatitis-induced systemic inflammation,
      particularly pulmonary injury. Rats with AP-associated lung injury were induced
      by multiple doses of caerulein, which was demonstrated in the previous studies.
      Three injections of losartan (200 microg/ kg/h) were given 30 min prior to the
      first injection of caerulein. The results demonstrated that caerulein injections
      resulted in significant increases in pancreatic and pulmonary myeloperoxidase
      (MPO) activities, and losartan treatment attenuates these effects. Lung
      microvascular permeability was also significantly improved by losartan treatment.
      Losartan prevented caerulein-induced pancreatic and pulmonary morphological
      alterations, but not elevations in serum alpha-amylase or pancreas/body weight
      ratio. These data indicate that losartan treatment can attenuate pancreatic and
      lung injury. Thus, the implication is that a blockade of AT1 receptors may have a
      clinical application for the treatment of AP and, perhaps more importantly,
      subsequent pulmonary complications.

PMID- 16443294
TI  - Factor substitution in nursing homes.
AB  - This paper studies factor substitution in one important sector: the nursing home
      industry. Specifically, we measure the extent to which nursing homes substitute
      materials for labor when labor becomes relatively more expensive. From a policy
      perspective, factor substitution in this market is important because materials
      intensive methods of care are associated with greater risks of morbidity and
      mortality among nursing home residents. Studying longitudinal data from 1991 to
      2000 on nearly every nursing home in the United States, we use the method of
      instrumental variables (IV) to address measurement error in nursing home wages.
      The results from the IV models yield evidence of factor substitution: higher
      nursing home wages are associated with greater use of psychoactive drugs and
      lower quality.

PMID- 16443295
TI  - Development of a real-time NASBA assay for the detection of Campylobacter jejuni
      cells.
AB  - The objectives of this study were the development of a real-time NASBA assay for
      the detection of Campylobacter jejuni mRNA and the evaluation of its potential to
      determine the viability of the detected C. jejuni cells. A set of specific
      primers and probes was chosen to amplify the mRNA of the tuf-gene and the GTPase
      gene. Only the tuf-assay was able to detect as low as 10(2) cells per NASBA
      reaction and was specific for Campylobacter. However, as the assay was able to
      detect dead cells, it cannot be used to demonstrate the viability of C. jejuni
      cells. The tuf-gene mRNA is no good viability indicator due to its stability.

PMID- 16443296
TI  - Patent pools and diagnostic testing.
AB  - There is increasing concern that overlapping patents in the field of genetics
      will create a costly and legally complex situation known as a patent thicket,
      which, along with the associated issues of accumulating royalty payments, can act
      as a disincentive for innovation. One potential means of preventing this is for
      the patent holders to enter into a so-called patent pool, such as those
      established in the electronics and telecommunications industries. Precedents for
      these also exist in the field of genetics, notably with the patents pertaining to
      the SARS genome. In this review, we initially address the patent pool concept in
      general and its application in genetics. Following this, we will explore patent
      pools in the diagnostic field in more detail, and examine some existing and novel
      examples of patent pools in genetics.

PMID- 16443297
TI  - Referral rates and trends in radiotherapy as part of primary treatment of cancer
      in South Netherlands, 1988-2002.
AB  - BACKGROUND AND PURPOSE: To study referral rates and time trends in the use of
      primary radiotherapy (RT). PATIENTS AND METHODS: The proportion and number of
      irradiated patients were calculated in a population-based setting among 58,436
      cancer patients diagnosed between 1988 and 2002. RESULTS: The number of patients
      receiving RT within 6 months of diagnosis (RT6mo) increased by about 3.3%
      annually, the proportion of all incident cases that received RT6mo remained
      stable (+/-30%). Only 20% of elderly patients (75+) received RT6mo. The
      proportion of cancer patients that received RT6mo increased markedly between 1988
      1992 and 1998-2002 for patients with prostate cancer (15 and 28%, respectively),
      rectal cancer (33 and 43%) and brain tumours (48 and 67%). The absolute number of
      irradiated breast cancer patients increased 30% between 1988 and 2002. Among
      patients with rectal cancer, a shift occurred from postoperative to preoperative
      RT since 1995. The percentage of irradiated patients with stage I endometrial
      cancer decreased from 47% in 1988-1992 to 15% in 1998-2002. CONCLUSIONS: The
      percentage of cancer patients who received primary RT remained stable throughout
      1988-2002, being consistently lower for older patients. The increased number of
      irradiated patients was due mainly to earlier detection and the ageing of the
      population. To clarify the overall percentage of patients irradiated, population
      based studies on RT given after 6 months since diagnosis are warranted.

PMID- 16443298
TI  - Peptidergic and catecholaminergic synaptic contacts onto nucleus preopticus
      medianus neurons projecting to the subfornical organ in the rat.
AB  - The nucleus preopticus medianus (POMe) is known to be a key site in regulation of
      cardiovascular and body fluid homeostasis. To clarify the regulation mechanism to
      the POMe, the innervation pattern of synapses made by axon terminals
      immunoreactive to beta-endorphin, neuropeptide Y and tyrosine hydroxylase onto
      POMe neurons projecting to the subfornical organ (SFO) was investigated in the
      rat. After injection of a retrograde tracer, wheat germ agglutinin-conjugated
      horseradish peroxidase-colloidal gold complex, into the SFO, many neurons were
      retrogradely labeled in the POMe, more frequently in its dorsal part. Electron
      microscopy of the POMe revealed that beta-endorphin- and tyrosine hydroxylase
      immunoreactive axon terminals formed predominantly axo-somatic synapses, and
      neuropeptide Y-immunoreactive axon terminals formed more axo-dendritic than axo
      somatic synapses with retrogradely labeled neurons. The present localization
      patterns of POMe neurons retrogradely labeled from the SFO and the type of
      synapses of axon terminals immunoreactive to three neurochemical markers on these
      neurons were compared to those of POMe neurons retrogradely labeled from the
      paraventricular hypothalamic nucleus demonstrated in our previous report.

PMID- 16443299
TI  - Survey of the mycobiota of Spanish malting barley and evaluation of the mycotoxin
      producing potential of species of Alternaria, Aspergillus and Fusarium.
AB  - The present work deals with the toxigenic mycobiota occurring in Spanish malting
      barley and the capability for producing mycotoxins by several important toxigenic
      fungi. One hundred and eighty seven samples of malting barley were gathered from
      Spanish breweries before processing. One hundred and fifty kernels per sample
      were surface-sanitized with a 2% sodium hypochlorite solution and incubated on
      three culture media. The most abundant fungi were species of Alternaria,
      Aspergillus, Penicillium and Fusarium, which were present in 93%, 82.3%, 57.8%
      and 27.8% of the samples, respectively. To evaluate their mycotoxin producing
      potential a number of isolates belonging to each genus, except Penicillium, were
      randomly selected and incubated on culture media known to be appropriate for
      production of mycotoxins. Alternariol and alternariol monomethyl ether were
      produced by 26.7% of Alternaria spp. isolates (all belonged to Alternaria
      alternata). All tested isolates of F. verticillioides produced fumonisin B(1)
      (FB(1)) and 61.3% of them produced fumonisin B(2) (FB(2)), whereas FB(1) was
      synthesized by 83.3% and FB(2) by 77.8% of F. proliferatum isolates. Twenty
      percent of the isolates of the Aspergillus flavus/A. parasiticus group had the
      capability to produce aflatoxin B(1) and aflatoxin B(2). Thirty out of 34
      isolates of F. graminearum produced deoxynivalenol and zearalenone whereas the
      other 4 isolates produced nivalenol. Ochratoxin A was detected in 75% and 15% of
      isolates of Aspergillus section Nigri and A. ochraceus, respectively. This is the
      first survey carried out in Spain on the toxigenic mycobiota contaminating
      malting barley in breweries and the mycotoxin producing capacity of several
      species. The information obtained is useful for assessing the risk of mycotoxins
      in beer.

PMID- 16443300
TI  - Isolation of epiphytic yeasts with potential for biocontrol of Aspergillus
      carbonarius and A. niger on grape.
AB  - Antagonistic yeasts were isolated from the epiphytic flora associated with grape
      berries cv. Negroamaro and identified at species level using molecular methods. A
      total of 144 yeast isolates were tested in a preliminary screening on agar to
      select isolates showing a killer activity against Aspergillus carbonarius and A.
      niger, the main species responsible for the accumulation of ochratoxin A in
      grape. Twenty-eight yeast isolates were selected for their inhibitory effects on
      the above fungal species and assayed by an in vitro nutritional competition test
      for their antagonistic capacity towards three selected ochratoxigenic strains.
      Six yeast isolates belonging to five species, namely 2 isolates of Issatchenkia
      orientalis and one each of Metschnikowia pulcherrima, Kluyveromyces
      thermotolerans, Issatchenkia terricola and Candida incommunis, were finally
      selected and screened on wounded grape berries for their ability to inhibit
      infection by ochratoxigenic moulds. With the exception of the K. thermotolerans
      isolate, when inoculated at 10(9) CFU/wound, the other five challenger yeasts
      reduced the A. carbonarius and A. niger colonization on grape berry (P<0.05). In
      particular, the best antagonistic activity was shown by the two I. orientalis
      isolates. Results suggest that antagonist yeasts with the potential to control A.
      carbonarius and A. niger on grape can be found among the microflora associated
      with the berries.

PMID- 16443301
TI  - Effect of water activity on ochratoxin A production by Aspergillus niger
      aggregate species.
AB  - The effect of water activity (a(w)) (0.82-0.99) on growth and ochratoxin A (OTA)
      production by twelve Aspergillus niger aggregate strains, cultured in Czapek
      Yeast Autolysate agar (CYA) and Yeast Extract Sucrose agar (YES), was studied for
      an incubation period of 30 days. The strains were selected to include diverse
      sources, different reported abilities to produce OTA and different ITS-5.8 S rDNA
      Restriction Fragment Length Polymorphism (RFLP) pattern. They were characterized
      by Random Amplification of Polymorphic DNA (RAPD) and ITS-5.8 S rDNA and 28 S
      rDNA (D1/D2) sequencing. Regardless of the a(w) value tested, YES was a better
      culture medium than CYA for OTA production. The a(w) range for OTA production was
      narrower than that for growth. OTA was produced from 0.90, 0.92, 0.94 or 0.96 to
      0.99 a(w) depending on the strain and the culture medium. The molecular study
      differentiated strains into two groups which corresponded to the RFLP types N and
      T although it did not distinguish them by their source of isolation or OTA
      producing abilities. Our results show that A. niger aggregate strains are able to
      grow and produce OTA over a wide a(w) range. These results will lead to a better
      understanding of the contribution of A. niger aggregate in OTA contamination of
      food and feed.

PMID- 16443302
TI  - Phylogenetic analysis of Portuguese bovine viral diarrhoea virus.
AB  - Bovine viral diarrhoea virus (BVDV) infections are an important cause of
      morbidity and mortality worldwide in dairy and beef cattle. To date, little is
      know about BVDV genotypes circulating in Portugal. For this purpose, a fragment
      within the 5'-untranslated region (5'-UTR) from 34 Portuguese field strains of
      BVDV was amplified by RT-PCR, cloned and sequenced. A maximum-likelihood
      phylogenetic analysis revealed that most of viruses, originated from cattle from
      different regions of the country, belong to BVDV type 1 (BVDV-1), genotypes 1b (n
      = 19), 1a (n = 6), 1d (n = 3) and 1e (n = 3); whereas three viruses clustered in
      BVDV type 2 (BVDV-2). The results from this study demonstrate that BVDV-lb is the
      most prevalent genotype and also shows the presence of BVDV-2 in Portugal.

PMID- 16443303
TI  - Efficient inhibition of hepatitis B virus replication by small interfering RNAs
      targeted to the viral X gene in mice.
AB  - The hepatitis B virus (HBV), as a major cause of acute and chronic hepatitis in
      humans, contains a partial double-stranded circular DNA genome of 3.2kb that is
      transcribed into the 3.5-, 2.4-, 2.1-, and 0.7-kb viral transcripts by the host
      RNA polymerase II. The HBV X (HBx) gene is consistently expressed in all four HBV
      viral mRNAs and thus an ideal target for developing viral inhibitors via a gene
      therapeutic approach. In this study, we show that two HBx-specific small
      interfering RNAs (siRNA), HBx1 and HBx3, significantly decrease both viral RNA
      and protein levels, and completely block replication in cultured cells co
      transfected with a siRNA expression plasmid and an HBV replication-competent
      vector. To further confirm these antiviral activities of selected siRNAs in small
      animals, we established acute and chronic HBV mouse models by hydrodynamic
      injection of this plasmid containing the full-length HBV genome. Selected HBx
      specific siRNAs also induced a significant anti-viral effect in living animals.
      Our findings should facilitate the development of an alternative therapeutic
      agent against HBV infection, particularly HBV-derived hepatocellular carcinoma
      (HCC) in which HBx has been known as one of the major pathological factors.

PMID- 16443305
TI  - Do you like the sight or the feel of milk in coffee? Ecology and effortful
      attention in differential acuity and preference for sensed effects of milk
      substitute in vended coffee.
AB  - A rapid method of discrimination scaling was used to measure individuals' acuity
      for levels of a complex stimulus perceived through several sensory modalities at
      once in a familiar context. The stimulus was a replacement for fresh milk used in
      vended coffee. The two experiments reported here compared the performance of
      ratings of the coffee's milkiness and creaminess when assessors were limited to
      the use of visual and/or olfactory cues. Better discrimination by milkiness
      ratings was observed during normal drinking and in a visual-only condition than
      when only oronasal or oral cues were available. Ratings relative to each
      assessor's ideal level of milkiness or creaminess showed diversity between
      assessor-preferred visual and oral characteristics of the milk substitute.
      However, instructing the assessor to attend to a particular aspect of the sample
      did not prevent the use of a better-discriminated characteristic if available to
      the senses. These results showed that the acceptability of a beverage or food
      depends more on the perceptible material than on efforts to direct attention to
      particular aspects.

PMID- 16443304
TI  - The accumulation of deleterious mutations in rice genomes: a hypothesis on the
      cost of domestication.
AB  - The extent of molecular differentiation between domesticated animals or plants
      and their wild relatives is postulated to be small. The availability of the
      complete genome sequences of two subspecies of the Asian rice, Oryza sativa
      (indica and japonica) and their wild relatives have provided an unprecedented
      opportunity to study divergence following domestication. We observed
      significantly more amino acid substitutions during rice domestication than can be
      expected from a comparison among wild species. This excess is disproportionately
      larger for the more radical kinds of amino acid changes (e.g. Cys<-->Tyr). We
      estimate that approximately a quarter of the amino acid differences between rice
      cultivars are deleterious, not accountable by the relaxation of selective
      constraints. This excess is negatively correlated with the rate of recombination,
      suggesting that 'hitchhiking' has occurred. We hypothesize that during
      domestication artificial selection increased the frequency of many deleterious
      mutations.

PMID- 16443307
TI  - Isolation and characterization of a novel small cardioactive peptide-related
      peptide from the brain of Octopus vulgaris.
AB  - A novel small cardioactive peptide (SCP)-related peptide (oct-SCPRP: Ser-Asn-Gly
      Tyr-Leu-Ala-Leu-Pro-Arg-Gln-NH2) was isolated from the brain of the octopus
      (Octopus vulgaris). cDNA encoding this precursor protein was cloned. Oct-SCPRP
      was shown to evoke contraction in the radula protractor muscle, and the precursor
      protein was highly homologous to the SCP family in the Mollusk but did not encode
      a related peptide, SCPB. The expression of oct-SCPRP mRNA was present not only in
      the peripheral nervous system (PNS) which is a motor center for the control of
      feeding, but also in the central nervous system (CNS) which is capable of complex
      analysis, learning, and controls behaviors.

PMID- 16443306
TI  - Modulatory roles of the NPFF system in pain mechanisms at the spinal level.
AB  - The possible roles of the NPFF system in pain processing are summarized from the
      viewpoints of (1) biological activities of NPFF, (2) anatomical distribution of
      NPFF and its receptor(s) and (3) the regulation of NPFF and receptor(s) in animal
      models of pain. NPFF and NPFF analogues were found to have analgesic,
      pronociceptive and morphine modulating activities. Since the isolation of NPFF,
      several other RF-NH2 peptides have been identified and some of them were found to
      have nociceptive or morphine modulating activity. Depending on the
      pharmacological doses and locations of administration, NPFF may exhibit the
      biological activities of other structurally related RF-NH2 peptides thus
      complicating NPFF bioactivity studies and their interpretation. Acid sensing ion
      channels were found to respond to RF-NH2 peptides including NPFF, raising the
      possibility that interaction of NPFF and acid sensing ion channels can modulate
      nociceptive activity. NPFF and NPFF receptor mRNAs are highly expressed and
      localized in the superficial layers of the dorsal cord, the two genes are also in
      dorsal root ganglia though at much lower level. The spinal NPFF system is up
      regulated by peripheral inflammation in the rat. Furthermore,
      immunohistochemically, NPFF receptor 2-protein was demonstrated to be increased
      in the primary afferents in the spinal cord of rats with peripheral inflammation.
      Regulation and localization of spinal NPFF systems, taken together with the
      analgesic bioactivity of intrathecally administered NPFF, strongly suggest
      involvement of spinal NPFF system in pain processing.

PMID- 16443308
TI  - Synthesis of compounds with antiproliferative activity as analogues of prenylated
      natural products existing in Brazilian propolis.
AB  - This work describes the syntheses and antitumoral properties of five prenyl
      compounds from which antiproliferative activities were predicted by using the
      TOPS-MODE approach, a computational method for drug design. The syntheses of 2-(3
      methylbut-2-enyloxy)acetophenone (2), 2-hydroxy-5-(3-methylbut-2
      enyl)acetophenone (3), 2-hydroxy-3-(1,1-dimethylallyl)acetophenone (4), and 5-(3
      methylbut-2-enyl)-2-(3-methylbut-2-enyloxy)acetophenone (5) were realized by O
      prenylation of phenolic compounds with prenyl bromide and by Claisen
      rearrangement, respectively. Reaction of 2-hydroxy-5-(3-methylbut-2
      enyl)acetophenone 3 under Vilsmeier-Haack conditions with phosphoryl chloride and
      N,N-dimethylformamide yielded 6-(3-methylbut-2-enyl)chromone-3-carbaldehyde (6).
      The compounds were tested for their cytotoxicity toward a diverse panel of
      cultured human tumor cell lines. Compound 3 showed significant selective
      cytotoxic activity (IC(50) < 9 microg/ml).

PMID- 16443309
TI  - Dendritic cells transduced with recombinant adenoviruses induce more efficient
      anti-tumor immunity than dendritic cells pulsed with peptide.
AB  - Transduction with recombinant, replication-defective adenovirus (AdV) vectors
      encoding a transgene is an efficient method for gene transfer into murine or
      human dendritic cells (DC). We previously reported that human dendritic cells
      transduced with recombinant adenovirus encoding the CEA gene (AdVCEA) can
      effectively induce antigen-specific cytotoxic T lymphocytes (CTL) in vitro. In
      this study, the efficacy of vaccination using AdVCEA-transduced DC was compared
      with peptide-pulsed DC in terms of the antigen-specific CTL activity and anti
      tumor immunity to MC38/CEA2 in a murine tumor model. AdVCEA-transduced DC
      increased antigen-specific T-cell proliferation, augmented the number of IFN
      gamma secreting T-cells and induced potent CEA-specific CTL capable of lysing
      target cells pulsed with CEA peptide, as well as MC38/CEA2 expressing CEA,
      compared to peptide-pulsed DC. Moreover, vaccination of mice with AdVCEA
      transduced DC induced a potent protective and therapeutic anti-tumor immunity to
      MC38/CEA2 in a subcutaneous model. These data suggest that AdVCEA-transduced DC
      appears to be superior to peptide-pulsed DC for the induction of anti-tumor
      immunity against tumor cells; this occurs through augmentation of the antigen
      specific CTL response and may be used as an efficient DC-based tumor vaccine
      applicable to clinical care.

PMID- 16443310
TI  - The trapezium: a new location for an aneurysmal bone cyst.

PMID- 16443311
TI  - Changed vegetation composition in coniferous forests near to motorways in
      Southern Germany: the effects of traffic-born pollution.
AB  - To estimate the effect of traffic emissions on the vegetation composition of
      coniferous forests near to motorways, three transects of 520 m length were
      studied by analysing vegetation composition, soil parameters and deposition data
      in the Munich-area, Southern Germany. The detected patterns suggest that
      motorways have an impact on the vegetation composition in the neighbourhood of
      roads. Depending on the wind direction, the influences of the motorways reaches
      up to 230 m on downwind side and up to 80 m on upwind side. The vegetation is
      mainly affected by the deposition of nitrogen deriving from fuel combustion and
      by basic substances added to road salt. By monitoring vegetation changes near to
      motorways, it is possible to estimate the areas where harmful alterations of the
      ecosystem can be expected.

PMID- 16443312
TI  - Effective remediation of grossly polluted acidic, and metal-rich, spoil heap
      drainage using a novel, low-cost, permeable reactive barrier in Northumberland,
      UK.
AB  - A permeable reactive barrier (PRB) for remediation of coal spoil heap drainage in
      Northumberland, UK, is described. The drainage has typical chemical
      characteristics of pH<4, [acidity]>1400 mg/L as CaCO3, [Fe]>300 mg/L, [Mn]>165
      mg/L, [Al]>100mg/L and [SO4]>6500 mg/L. During 2 years of operation the PRB has
      typically removed 50% of the iron and 40% of the sulphate from this subsurface
      spoil drainage. Bacterial sulphate reduction appears to be a key process of this
      remediation. Treatment of the effluent from the PRB results in further
      attenuation; overall reductions in iron and sulphate concentrations are 95% and
      67% respectively, and acidity concentration is reduced by an order of magnitude.
      The mechanisms of attenuation of these, and other, contaminants in the drainage
      are discussed. Future research and operational objectives for this novel, low
      cost, treatment system are also outlined.

PMID- 16443313
TI  - Does prenatal care increase access to child immunization? Gender bias among
      children in India.
AB  - Prenatal care appears to serve as a trigger in increasing the chances for access
      to subsequent health care services. Although several previous studies have
      investigated this connection, none have focused specifically on how parents'
      behavior differs before and after learning the gender of their babies.
      Investigating parents' behavioral changes after the child's birth provides a
      quasi-natural experiment with which to test the gender discrimination hypothesis.
      This issue was examined here, using a rich family health survey data set from
      India. We find evidence for the triggering effect of prenatal care on
      immunization only among rural boys, but we find no compelling evidence for this
      effect among other sub-samples. This finding suggests two things, which are not
      mutually exclusive. One is that the information spillover from prenatal care has
      a much larger impact in rural areas, where alternative sources of information are
      scarce, compared with urban areas. The other is that the sex of a child is a
      critical factor in producing different levels of health care behavior in rural
      areas, where sons are favored and more valued than in urban areas.

PMID- 16443314
TI  - Social support and self-rated health revisited: is there a gender difference in
      later life?
AB  - This study examines the physical, behavioral, emotional and social determinants
      of self-rated health among Chinese older persons, and investigates if the effect
      of social support varies by gender. A representative sample of 1589 elderly
      community dwellers in Hong Kong were interviewed using a structured
      questionnaire. Gender difference in the effect of social support was tested by an
      interaction term, 'gender x social support', in a hierarchical regression
      analysis. The frequency of falling ill, the number of chronic illnesses, sleep
      quality, mobility and positive emotions were most important determinants of self
      rated health. The effect of social support was completely redundant when these
      factors were taken into account. The interaction term 'gender x social support'
      was significant and indicated a stronger effect for women, but the effect size
      was negligible (adding only 0.3% to the explained variance). This suggests that
      the effect of social support by and large is gender free. These findings suggest
      a high degree of similarity in the determinants of self-rated health between
      Western and Chinese older populations.

PMID- 16443315
TI  - The neurocircuitry of obsessive-compulsive disorder and disgust.
AB  - Recent evidence from human research has indicated that discrete regions of the
      brain control different basic emotions. Whether the recognition and formulation
      of emotions truly stem from compartmentalized systems or arise from a
      multidimensional framework has yet to be elucidated, however. Disgust is a basic
      emotion that has been hypothesized to constitute an evolutionary function of
      contamination and disease avoidance. Disgust involves the appraisal of objects
      and events for their potential role in contamination, and OCD conceivably
      involves a dysfunction of this appraisal process. Disgust sensitivity has been
      shown to be positively correlated with OCD and to significantly predict
      contamination fear. Likewise, functional imaging studies of OCD patients with
      contamination concerns demonstrate activation of the same neural regions with
      disgust-inducing pictures as symptom relevant stimuli. Therefore, the
      neurocircuits involved in disgust processing may be relevant to OCD and, in
      particular, the contamination subtype. This review focuses on describing what is
      known to date concerning the neurocircuitry of disgust, and its relevance to the
      apparent neurocircuitry of OCD.

PMID- 16443316
TI  - Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of
      immobility tests.
AB  - The present study was undertaken to investigate the effects of aqueous extract of
      Glycyrrhiza glabra L. (Family: Fabaceae), popularly known as liquorice, on
      depression in mice using forced swim test (FST) and tail suspension test (TST).
      The extract of G. glabra (75, 150, and 300 mg/kg) was administered orally for 7
      successive days in separate groups of Swiss young male albino mice. The dose of
      150 mg/kg of the extract significantly reduced the immobility times of mice in
      both FST and TST, without any significant effect on locomotor activity of mice.
      The efficacy of extract was found to be comparable to that of imipramine (15
      mg/kg i.p.) and fluoxetine (20 mg/kg i.p.). Liquorice extract reversed reserpine
      induced extension of immobility period of mice in FST and TST. Sulpiride (50
      mg/kg i.p.; a selective D2 receptor antagonist) and prazosin (62.5 microg/kg
      i.p.; an alpha1-adrenoceptor antagonist) significantly attenuated the extract
      induced antidepressant-like effect in TST. On the other hand, p
      chlorophenylalanine (100 mg/kg i.p.; an inhibitor of serotonin synthesis) did not
      reverse antidepressant-like effect of liquorice extract. This suggests that
      antidepressant-like effect of liquorice extract seems to be mediated by increase
      of brain norepinephrine and dopamine, but not by increase of serotonin. Monoamine
      oxidase inhibiting effect of liquorice may be contributing favorably to the
      antidepressant-like activity. Thus, it is concluded that liquorice extract may
      possess an antidepressant-like effect.

PMID- 16443317
TI  - The frequency of chromosomal abnormalities in patients with reproductive failure.
AB  - OBJECTIVE: To investigate the ratio of chromosomal abnormalities in recurrent
      fetal wastage. STUDY DESIGN: We conducted a study of the cytogenetic data of 645
      couples (1290 patients) with recurrent fetal wastage examined at the Department
      of Medical Biology and Genetics, Trabzon, Turkey. Couples who had first trimester
      miscarriages/abortion, preceded or followed by a second or third trimester fetal
      death/fetal abnormalities were recruited from Obstetrics and Gynecology Clinics
      for cytogenetics analysis. RESULTS: Chromosome abnormalities were found in 25
      (3.86%) patients. The chromosomal abnormalities were structural (3.71%) and
      numerical (0.15%). Polymorphisms of heterochromatin blocks and inv(9) were shown
      in 115 (17.51%) patients. CONCLUSIONS: Chromosome analyses are an important and
      necessary part of the etiological research in couples with recurrent fetal
      wastage.

PMID- 16443318
TI  - Protective effect of vascular endothelial growth factor (VEGF) in frozen-thawed
      granulosa cells is mediated by inhibition of apoptosis.
AB  - OBJECTIVES: This study was conducted to evaluate the involvement of apoptosis in
      the freeze-thaw process and to investigate the anti-apoptotic effect of vascular
      endothelial growth factor (VEGF) in the frozen-thawed granulosa cells. STUDY
      DESIGN: Isolated rat granulosa cells were cultured, frozen-thawed, and were
      cultured for 24h. Cell viabilities (by Trypan blue exclusion test) and apoptotic
      patterns (by Annexin-V/propidium iodide (PI) Double-Staining) were determined at
      each step. Apoptotic cell death was confirmed by following DNA degradation and
      caspase-3 activity. RESULTS: After freeze-thaw process and 24h of culture,
      reductions in the cellular viabilities and increases in the number of cells
      containing degraded DNA were lower in the VEGF pretreated group than in the
      control group (p<0.05). In the VEGF pretreated group, increases in the
      proportions of late apoptotic cells [Annexin-V (+)/PI (+)] were significantly
      lower and caspase-3 expression was prevented immediate after thawing (p<0.05).
      Furthermore, increases in the proportions of early apoptotic cells [Annexin-V
      (+)/PI (-)] and reductions in the proportions of viable cells [Annexin-V (-)/PI (
      )] were significantly lower in the VEGF pretreated group after culture for 24h
      (p<0.05). Of the different doses of VEGF pretreated, 50ng/ml was found to be most
      effective with respect to protecting frozen-thawed granulosa cells from
      cryoinjury. CONCLUSION: Granulosa cell damage induced by cryopreservation is
      mediated, at least in part, by an apoptotic process. Our preliminary results
      suggest that VEGF treatment before freeze-thaw process reduces rat ovarian
      granulosa cell damage by inhibiting apoptosis.

PMID- 16443319
TI  - Obstetric intensive care admissions: a 12-year review in a tertiary care centre.
AB  - OBJECTIVE: To review all pregnant women who required admission to an Intensive
      Care Unit (ICU) during pregnancy, childbirth or puerperium. STUDY DESIGN:
      Retrospective follow-up study in a tertiary care centre in The Netherlands. The
      files of all obstetric ICU admissions over the period 1990-2001 were reviewed.
      RESULTS: Over these 12 years, 142 women required ICU admission (0.76% of all
      deliveries, 0.70% of all adult ICU admissions). The most common reasons for ICU
      admission were (pre)eclampsia (62.0%) and obstetric haemorrhage (18.3%). Twenty
      seven out of 142 women (19.0%) were of non-caucasian origin. The most common
      therapeutic interventions were transfusion of erythrocytes (66.2%), caesarean
      section (50.7%) and artificial ventilation (44.4%). We observed seven maternal
      deaths (4.9%). CONCLUSION: We need better information about high-risk obstetric
      patients in order to prevent severe maternal morbidity and to improve maternal
      care. The high number of non-caucasian women requiring ICU admission indicates
      the need for a study into the role of ethnicity. We have initiated a nationwide
      confidential enquiry into the causes of severe maternal morbidity.

PMID- 16443320
TI  - Influence of spectral heterogeneity of prodan and laurdan solutions on the
      transfer of electronic energy to octadecyl rhodamine B.
AB  - Fluorescence quenching and resonance energy transfer have been studied by steady
      state fluorescence spectroscopy. The experimental and theoretical values for the
      rate constants of the electronic energy transfer (kET) and critical radius (R0)
      were determined for prodan and laurdan as donors and octadecyl rhodamine B as
      acceptor. The spectroscopic data show, that prodan and laurdan in solution create
      an inhomogeneous spectroscopic medium in which multi-channel luminescence
      phenomena take place. This finding indicated that the modified form of the Stern
      Volmer relation should be used for analyzing fluorescence quenching data. Results
      of performed studies point out, that dipole-dipole interaction is responsible for
      the resonance energy transfer from prodan and laurdan to octadecyl rhodamine B.
      The relative quenching efficiencies of both dyes depend on polarity of the medium
      and are higher for more polar solvent (AcN).

PMID- 16443321
TI  - Nephron-sparing surgery for renal cell carcinoma: detailed analysis of
      complications over a 15-year period.
AB  - PURPOSE: To assess the incidence of complications of conservative renal surgery
      for renal cell carcinoma in both elective and imperative indications, and its
      evolution over a 15 year period. PATIENTS AND METHODS: From 1988 to 2003, 127
      patients underwent partial nephrectomy or tumorectomy for renal cell carcinoma in
      our department. INDICATIONs were imperative in 42% (n = 53) and elective in 58%
      (n=74) of cases. Morbidity was retrospectively assessed according to four
      parameters: 1- Period of surgery: A, from 1988 to 1999 and B, from 2000 to 2003.
      2- INDICATION: elective vs. imperative. 3- experience of surgeon: senior vs.
      junior. 4- Nature of complications: minor or major. Comparative analysis was
      conducted using Chi-square and Fischer exact tests. RESULTS: Global incidence of
      complications was 30.7% (n = 39) corresponding to 18.1% minor (n = 23) and 12.6%
      (n = 16) major complications. Results show a moderate decrease of complication
      rate during Period B: 28.1% versus 32.9% during period A (p = 0.69).
      Complications occurred more frequently in imperative indications (49.1%) than in
      elective indications (17.6%) (p = 0.002), mostly regarding major complications
      (respectively 28.3% and 1.4%. (p < 0.001)). Overall re-intervention rate was
      15.7%: 22.6% in imperative and 10.8% in elective indications (p = 0.008). Mean
      length of hospital stay was 14.1 days and significantly longer during period A (p
      = 0.003) and in imperative indications (p = 0.009). CONCLUSION: In our study,
      conservative renal surgery has a significant rate of complications which is
      extremely variable regarding to different parameters. Most discriminating factor
      was indication: in imperative indications, we observed a high rate of major
      complications (28.3%) that we consider acceptable to prevent anephria in clearly
      informed patients. Major complications are exceptional in elective indications.
      Decreased incidence of complications during the later period (B) is modest, and
      the role played by systematic pedicular clampage is discussed. As results
      published in medical literature are difficult to compare, we agree with authors
      who recently proposed to standardize complications data analysis, using a gravity
      scale, in order to provide relevant information to patients about statistical
      risks before surgery.

PMID- 16443323
TI  - Adsorption of copper ions onto microwave stabilized heavy metal sludge.
AB  - Microwave stabilized heavy metal sludge was used as an adsorbent to remove the
      copper ions from aqueous solution. The adsorption characteristics of copper on
      the stabilized-sludge were studied by various models, such as Freundlich and
      Langmuir isotherm equation. Results show that the pH(zpc) of stabilized-sludge
      was at 9.2-9.5. Moreover, the adsorption of copper ions onto the stabilized
      sludge surface was mainly on account of the heterogeneous surface of the
      stabilized-sludge. In the dynamic study, the experimental data was fitted to the
      intraparticle diffusion model, pseudo-first order model and pseudo-second order
      model. However, the experimental data was only well correlated with pseudo-second
      order model with the correlation coefficient>0.995. Furthermore, both Freundlich
      and Langmuir isotherm equations were found to represent the measured adsorption
      data well. From the Langmuir equation, the adsorption capacity increased from 18
      to 28 mg/g as the temperature rose from 15 to 55 degrees C, since this adsorption
      process was an endothermic reaction. After this adsorption process, copper ions
      can be concentrated on and in a small bead and recovery efficiently.

PMID- 16443322
TI  - Estrogen mediated cross talk between the ovary and pituitary somatotrope. Pre
      ovulatory support for reproductive activity.

PMID- 16443325
TI  - A comparison study of cerebral protection using Ginkgo biloba extract and
      Losartan on stroked rats.
AB  - It has been well documented that oxidative stress is involved in stroke.
      Currently, many neuroprotective strategies have been targeted at molecules that
      are able to act as an oxidant to intervene with free-radical mediated apoptosis
      in the ischemic penumbra. In particular, natural products which contain
      antioxidant properties have undoubtedly efficacious for stroke treatment. In the
      current study, therapeutic effects of Ginkgo biloba extract (EGb) against
      cerebral protection in Wistar rats underwent middle cerebral artery occlusion
      (MCAO) was evaluated. A comparison study was conducted by using Losartan, an
      antihypertensive drug. Gene expression levels of pro-apoptotic genes (AT2
      receptor, Fas, Bax and Bcl-xS) have shown to have significant reduction by EGb-
      and Losartan-treated groups as compared to vehicle group. Significant reduction
      of immunoreactivity of protein production of these genes, together with least
      nuclear green fluorescence observed in TUNEL, EGb, as an antioxidant drug, is
      concluded to have potent and promising therapeutic effect for stroke treatment.

PMID- 16443324
TI  - Sorption of copper(II) ion from aqueous solution by Tectona grandis l.f. (teak
      leaves powder).
AB  - Studies on a batch sorption system using Tectona grandis l.f. as adsorbent was
      investigated to remove copper(II) from aqueous solutions. The adsorption
      experiments were performed under various conditions such as different initial
      concentrations, pH, adsorbent dosage and adsorbent particle size. The data showed
      that 0.1 g of Tectona grandis l.f. was found to remove 71.66% of 20 mg/L
      copper(II) from 30 mL aqueous solution in 180 min. The experimental equilibrium
      data were adjusted by the adsorption isotherms from Langmuir and Freundlich
      models and their equilibrium parameters were determined. The best-adjusted model
      to the experimental equilibrium data for Tectona grandis l.f. was the Langmuir
      model. Using the Langmuir model equation, the monolayer sorption capacity of
      Tectona grandis l.f. was evaluated and found to be 95.40 mg/g. The optimum pH
      value was found to be 5.5. The pseudo-first-order and pseudo-second-order kinetic
      models were used to describe the kinetic data. The dynamic data fitted the pseudo
      second-order kinetic model.

PMID- 16443326
TI  - Inhibition of the ERK/MAP kinase pathway attenuates heme oxygenase-1 expression
      and heme-mediated neuronal injury.
AB  - Hemin is an oxidant that accumulates in intracranial hematomas. Its neurotoxicity
      is increased by its breakdown, which is catalyzed by the heme oxygenase (HO)
      enzymes. In this study we tested the hypothesis that inhibiting signaling events
      mediating HO-1 induction would protect cultured cortical neurons from hemin. A
      fivefold increase in HO-1 expression was observed in mixed neuron-astrocyte
      cultures 4h after hemin exposure. This was markedly reduced by the ERK pathway
      inhibitor U0126. The JNK inhibitor SP600125 had a weak but statistically
      significant effect, while the p38 inhibitor SB239063 was ineffective. Hemin
      neurotoxicity, as assessed by LDH release, propidium iodide staining, and
      malondialdehyde assay, was also prevented by U0126 but not by SB239063; SP600125
      had little or no effect. Consistent with reduced iron release, ferritin
      expression was also attenuated by U0126, while cell hemin accumulation was
      increased. These results suggest that targeting the ERK pathway may prevent HO-1
      induction in response to hemin, and reduce neuronal injury.

PMID- 16443327
TI  - Chronic exposure to GSM 1800-MHz microwaves reduces excitatory synaptic activity
      in cultured hippocampal neurons.
AB  - The world wide proliferation of mobile phones raises the concern about the health
      effects of 1800-MHz microwaves on the brain. The present study assesses the
      effects of microwave exposure on the function of cultured hippocampal neurons of
      rats using whole cell patch-clamp analysis combined with immunocytochemistry. We
      showed that chronic exposure (15 min per day for 8 days) to Global System for
      Mobile Communication (GSM) 1800-MHz microwaves at specific absorption rate (SAR)
      of 2.4 W/kg induced a selective decrease in the amplitude of alpha-amino-3
      hydroxy-5-methyl-4-soxazole propionic acid (AMPA) miniature excitatory
      postsynaptic currents (mEPSCs), whereas the frequency of AMPA mEPSCs and the
      amplitude of N-methyl-D-aspartate (NMDA) mEPSCs did not change. Furthermore, the
      GSM microwave treatment decreased the expression of postsynaptic density 95
      (PSD95) in cultured neurons. Our results indicated that 2.4 W/kg GSM 1800-MHz
      microwaves may reduce excitatory synaptic activity and the number of excitatory
      synapses in cultured rat hippocampal neurons.

PMID- 16443328
TI  - Association studies of genetic polymorphism, environmental factors and their
      interaction in ischemic stroke.
AB  - Genetic background plays an important role in susceptibility to ischemic stroke.
      Our aim was to investigate the association of genetic polymorphisms and ischemic
      stroke and to evaluate their interaction with environmental risk factors in the
      Chinese population. Angiotensin-converting enzyme (ACE) gene I/D polymorphism,
      apolipoprotein E (ApoE) gene polymorphism, methylenetetrahydrofolate reductase
      (MTHFR) gene 677C/T polymorphism, and beta fibrinogen (Fgbeta) gene 148C/T
      polymorphism were analyzed in 100 patients and 100 matched controls. The subjects
      were genotyped by polymerase chain reaction (PCR) amplification and denaturing
      high-performance liquid chromatography (DHPLC) analysis. Persons with the Fgbeta
      CT/TT, MTHFR CT/TT, and ACE ID/DD genotypes had an elevated incidence of ischemic
      stroke (OR 3.907, 95% CI, 1.160-13.162, P=0.028). Smokers with the Fgbeta CT/TT
      or APOEepsilon4epsilon3 genotype, as well as individuals with the Fgbeta CT/TT
      genotype who consumed alcohol were more likely to develop a stroke. The data
      indicate that certain unfavorable genotypic combinations act synergistically in
      the development of ischemic stroke in the Chinese population. Synergism was also
      observed between genotype and environmental risk factors. This study may
      facilitate the development of a strategy to effectively prevent ischemic strokes.

PMID- 16443329
TI  - Smoking as a decision among pregnant and non-pregnant women.
AB  - OBJECTIVES: The purpose was to examine values and beliefs related to smoking, and
      to test the validity of a decision model based on the product of the value of
      smoking-related events and states, and the belief that these will occur, (in
      decision research labeled Expected Utility, or EU). METHODS: Over a two-week
      period eighty women, divided into subgroups consisting of pregnant vs. non
      pregnant women, and those intending vs. those not intending to quit smoking,
      performed evaluations of values and beliefs for the two conditions of quitting
      and not quitting smoking. RESULTS: For both pregnant and non-pregnant women
      expected utility of smoking was negative. Of all the four groups pregnant women
      not intending to quit smoking estimated the expected utility of smoking as least
      negative. CONCLUSIONS: A decision analytic approach is applicable to describe the
      addictive behavior of smoking. Values as well as beliefs about smoking should be
      stressed in smoking cessation programs, especially among pregnant women.

PMID- 16443330
TI  - When risk factors combine: the interaction between alcohol and smoking for
      aerodigestive cancer, coronary heart disease, and traffic and fire injury.
AB  - BACKGROUND: Alcohol and tobacco are responsible for a significant amount of
      burden of disease, but some diseases may be a result of the interaction between
      these two risk factors. METHODS: Systematic literature review identified articles
      on the interaction of alcohol and smoking on a number of outcomes related to both
      risk behaviours. RESULTS: The interaction of smoking and alcohol significantly
      increases risk for aerodigestive cancers, and may increase risk for traffic
      injury and fire injury, but there were very few quality studies on injury. The
      indication that the cardioprotective effect of alcohol on coronary heart disease
      is only valid for smokers, but this result is inconclusive because of small
      evidence base. CONCLUSIONS: The interaction between smoking and alcohol
      consumption seems to be responsible for a significant amount of disease.
      Unfortunately, little is known on the mechanisms and details of this interaction
      on disease outcomes. Future studies, especially for coronary heart disease and
      injury outcomes, are warranted.

PMID- 16443331
TI  - Effectiveness of specialist group treatment for smoking cessation vs. one-to-one
      treatment in primary care.
AB  - OBJECTIVE: Using a quasi-experimental design, this paper contributes to an
      important debate about the most effective form of psychological treatment to aid
      smoking cessation: group treatment provided by specialists or one-to-one
      treatment provided in the community by primary care nurses or pharmacists.
      METHODS: Data were routinely collected from 1501 clients of a large London stop
      smoking service that offered both group and one-to-one treatment. RESULTS: A
      quarter (25%) of the clients were continuously abstinent 4 weeks post-quit: 30%
      for those receiving group treatment and 19% for one-to-one (Fisher's exact [2
      sided]<.001). The difference between the specialist and community-based treatment
      remained after all possible confounding factors were controlled for (OR: 2.27,
      p<.001). CONCLUSIONS: In the same service with the same management structure and
      training programme, group treatment offered by the specialist service yielded
      higher success rates than counselling by trained primary care nurses and
      pharmacists.

PMID- 16443332
TI  - What do European badgers (Meles meles) know about the spatial organisation of
      neighbouring groups?
AB  - European badgers (Meles meles) live in groups. Although they can distinguish
      between a member of their own group, a member of a neighbouring group and a
      stranger, their ability to understand that neighbouring individuals belong to
      different groups inhabiting different places, and possibly to build up some
      representation of the spatial organisation of neighbouring groups remains to be
      shown. In this study, we conducted a pilot homing experiment to test such
      ability. Radio-collared badgers were displaced to the home ranges of neighbouring
      groups and their homing performances were compared to those of badgers displaced
      either to the periphery of their own group's home range or beyond the
      neighbouring home ranges. When released in their own home range, badgers homed
      rapidly and efficiently, whereas when released beyond the neighbouring groups'
      home ranges (whatever the distance) they did not home. In contrast, badgers
      released in the home range of a neighbouring group performed some random search
      there, before returning to their setts quite efficiently. These results suggest
      that badgers may consider their neighbours as members of different groups
      inhabiting different places close to their own home range, but their ability to
      build up some spatial representation of neighbourhood relationships could not be
      demonstrated.

PMID- 16443333
TI  - Do drug users in China who frequently receive detoxification treatment change
      their risky drug use practices and sexual behavior?
AB  - BACKGROUND: Relapse rates among treated drug users in China are high. We examined
      the associations between frequency of drug detoxification treatment and HIV
      related risky drug practices and sexual behavior. METHODS: A cross-sectional
      study was conducted among drug users in two Anhui province detoxification centers
      in 2003. RESULTS: A total of 312 drug users were recruited. Seventy-seven percent
      of the subjects had ever received two or more detoxification treatments. The
      median number of detoxification treatments received was three, with an
      interquartile range of two to five treatments. More than 7 in 10 (72%) ever
      injected drugs; 19% shared needles and syringes in the past 30 days; 40% of drug
      users reported having both regular and commercial sex partners in the past year
      and 48% reported having only regular sex partners. Multiple Poisson regression
      analysis documented that the frequency of detoxification treatment was not
      associated with a decrease in drug practice (injection or sharing needles) and in
      unprotected sex. CONCLUSION: Drug users who frequently received detoxification
      treatment did not change their risky drug use practices and sexual behavior.
      Effective behavioral interventions and substitution maintenance treatment should
      become an integral part of detoxification programs in China.

PMID- 16443335
TI  - Human Endogenous Retrovirus (HERV)-R family in primates: Chromosomal location,
      gene expression, and evolution.
AB  - Hitherto, full-length endogenous retrovirus (HERV)-R has been located at human
      chromosome 7q11.2, and mRNA and envelope proteins have been detected in placenta
      and a variety of other cell types. In the present study, using a probe derived
      from the gorilla fosmid library, we detected the paralogous locus (7q31.3) of the
      HERV-R env gene in human chromosome 7q11.2, and also determined the chromosomal
      location in apes and Old World monkeys. The HERV-R gene was not detected in New
      World monkeys or prosimians with FISH and PCR analyses. We determined the
      sequences of the HERV-R env genes obtained from the genomic DNA of primates using
      PCR and sequencing tools. Except for a HERV-R env sequence derived from gorilla
      DNA, the functional domains of putative envelope proteins are conserved,
      suggesting that those domains could have a functional capacity in the primate
      genome. In addition, we investigated the env gene expression of HERV-R in various
      human tissues and cancer cells. An RT-PCR approach indicated that the env gene
      was expressed in several human tissues (brain, prostate, testis, kidney,
      placenta, thymus, and uterus) and cancer cells (RT4, BT-474, MCF7, OVCAR-3, LOX
      IMVI, and AZ521). Taken together, our data could be of great use for
      understanding the evolutionary dynamics of HERV-R through primate radiation as
      well as the implications of its functional role in human tissues and cancers
      cells.

PMID- 16443334
TI  - The testis-specific apoptosis related gene TTL.6 underwent adaptive evolution in
      the lineage leading to humans.
AB  - The TTL.6 gene is a member of the tubulin-tyrosine ligase (TTL) family involved
      in apoptosis and preferentially expressed in the testis. We sequenced the coding
      region and part of the introns of TTL.6 in world wide human populations and five
      representative nonhuman primate species covering great apes, lesser ape and Old
      World monkey. The sequence substitution patterns of TTL.6 in primates
      demonstrated a sharp difference in evolutionary rates among different primate
      lineages. Our results indicated an accelerated evolution of TTL.6 in the human
      lineage, which was caused by Darwinian positive selection. Further analysis on
      sequence variations in human populations demonstrated an excess of derived common
      alleles, which was likely caused by genetic hitchhiking, an implication of recent
      positive selection on TTL.6 in human populations.

PMID- 16443336
TI  - Efficacy of different vasodilators on human umbilical arterial smooth muscle
      under normal and reduced oxygen conditions.
AB  - The ability of the smooth muscle of the human umbilical artery to relax may vary
      under physiological and pathological conditions. We investigated the
      responsiveness of that preparation to relaxation, as well as the influence of
      reduced oxygen condition on these responses. Rings of human umbilical arteries
      from full-term Caesarian deliveries were suspended in modified Krebs-Henseleit
      solutions bubbled with a gas mixture of 95% O2:5% CO2 (normal oxygen condition)
      or 2.5% O2:8% CO2 balanced with N2 (reduced oxygen condition). These rings were
      contracted with potassium chloride, serotonin or the thromboxane A2 mimetic
      U46619, before being exposed to either the nitrovasodilator sodium nitroprusside,
      the potassium channel opener levcromakalim or the calcium channel antagonist
      amlodipine. While sodium nitroprusside elicited relaxation in this blood vessel,
      the maximal relaxation to the nitric oxide donor was significantly smaller than
      that induced by levcromakalim and amlodipine. The nature of the constrictor agent
      used, or changes of oxygen conditions did not significantly affect the relaxation
      profile of this human blood vessel. These data suggest that the smooth muscle of
      the human umbilical artery may be less responsive to vasodilators that act via
      the nitric oxide pathway. Moreover, vascular responses of umbilical arterial
      smooth muscle to relaxing agents do not alter under hypoxic or different
      vasoconstricting conditions.

PMID- 16443338
TI  - Changes in the activity of soluble arylsulphatase during the post-hatch
      development and regression after light reduction of Japanese quail testes and
      epididymides.
AB  - This study demonstrates that specific activity of soluble arylsulphatase (AS)
      during post-hatch development of Japanese quail testes is the highest for testes
      weighing from 20 to 200mg, and then decreases as the weight of testes increases,
      while AS activity per g of wet tissue decreases steadily for testes weighing over
      20 to 30 mg. Total AS activity showed a steady increase with the increasing
      weight of testes. The highest increments in the enzyme activity concerned testes
      weighing up to 30 mg and those weighing from 30 to 150 mg. Mature animals with
      testes weighing from 2 to 4 g showed an equal level of total AS activity. Based
      on this data it is suggested that the changes found in the enzyme activity
      concern mainly arylsulphatase from Sertoli cells. Specific activity of AS in
      epididymides remains low until testes reach a weight of approximately 1g and then
      increases, reaching maximal values for epididymides from the testes of sexually
      mature animals. Testicular and epididymal regression induced by a short
      photoperiod (6L:18D) after 30 days of the experiment increases AS activity in the
      testes and reduces its activity in the epididymides to the values found in the
      early stages of development. Testes and epididymides in the earliest stage of
      post-hatch development are characterized by an elution profile of AS in which the
      form of the enzyme bound to the strong anion exchanger at pH 6.0 is predominant,
      while in mature animals the form of the enzyme unbound to the anion exchanger
      predominates in the testes and epididymides. After 30-day regression of the
      testes and epididymides, the form bound to the anion exchanger did not increase,
      which suggests that the organs do not return exactly to the stage before sexual
      maturity.

PMID- 16443337
TI  - Family stability during childhood and the risk to develop hypertensive diseases
      in pregnancy.
AB  - BACKGROUND: Parental care giving, divorce and death are associated with physical
      health as an adult. AIM: To investigate whether the structure of the nuclear
      family during childhood shows any correlation with the development of
      hypertensive diseases in pregnancy as an adult. STUDY DESIGN: Self-administered
      questionnaires were sent to 2600 women with hypertensive diseases in pregnancy
      and to 1484 controls. SUBJECTS: After confirmation of the diagnosis data from 842
      patients and 623 control women were evaluated. OUTCOME MEASURES: Type, number and
      involvement of different caregivers, parental separation, parental death.
      RESULTS: In both groups parental separation and parental death were found equally
      often. In all age groups during childhood fathers were involved significantly
      less often in care giving when women with hypertensive disorders in pregnancy
      were compared to control women (1st-3rd year 23.4%/17%, <0.0001; 4th-10th year
      25.7%/19.3%, <0.0001; 11th-18th year 30.1%/23.9%, <0.0001). The total number of
      caregivers involved was significantly higher in patients. CONCLUSIONS: The
      quality of parental care giving, i.e. the involvement of fathers and the total
      number of caregivers correlate with the risk to develop HDP. Further research is
      needed to specify underlying mechanisms and the relevant factors of the parent
      child relationship.

PMID- 16443339
TI  - Postprandial lipaemia in menopausal women with metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome (MetS) is associated with an increased
      incidence of coronary heart disease (CHD). Postprandial hypertriglyceridaemia is
      also associated with CHD. The aim of this study was to evaluate the postprandial
      lipaemia after an oral fat tolerance test (OFTT) in women with MetS. METHODS:
      OFTT, was given to 21 menopausal women with MetS (defined by the Adult Treatment
      Panel III) and to 12 healthy menopausal women. Triglyceride (TG) levels were
      measured before and 2, 4, 6 and 8h after the OFTT. The postprandial response was
      quantified by the areas under the curve (AUC) of TG levels. MetS women were
      subdivided according to body mass index (BMI) < or > or =30kg/m(2), and to
      fasting TG levels < or > or =150mg/dl. RESULTS: The response to the OFTT was
      significantly higher in the MetS group compared to healthy [AUC(S.D.), in
      mg/dl/h; 2014(933) versus 732(197), p<0.001]. The subjects with BMI < or > or
      =30kg/m(2) had similar fasting TG levels [157(60)mg/dl versus 158(67) mg/dl] and
      AUC [1975(898) versus 2072(1044), respectively]. The MetS women with TG> or
      =150mg/dl had higher AUC compared to those with TG<150mg/dl [2502(854) versus
      1281(441), p=0.002]. In linear regression analysis, where BMI, high-density
      lipoprotein cholesterol, fasting TG, HOMA-IR and QUICKI were the independent
      variables, only fasting TGs significantly predicted the AUC (coefficient
      B=11.866, p=0.008). CONCLUSIONS: The fasting TG concentration is the main
      determinant of postprandial lipaemia. The obesity state was not an additional
      determinant for exaggerated postprandial response in MetS women. The abnormal
      postprandial lipaemia could be added as an important metabolic disturbance to the
      MetS.

PMID- 16443340
TI  - The plasma glucose lowering action of Hei-Shug-Pian, the fire-processed product
      of the root of Aconitum (Aconitum carmichaeli), in streptozotocin-induced
      diabetic rats.
AB  - The anti-hyperglycemic action of Hei-Shug-Pian, the fire-processed product of the
      root of Aconitum (Aconitum carmichaeli), was investigated in streptozotocin
      induced diabetic (STZ-diabetic) rats. At 120 min following oral administration of
      Hei-Shug-Pian at doses ranging from 12.5 to 50 mg/kg, plasma glucose of STZ
      diabetic rats was found to be decreased in a dose-dependent manner. Under
      treatment conditions wherein plasma glucose was lowered, the uptake of glucose
      into soleus muscle was increased and the incorporation of glucose into glycogen
      of hepatocytes was enhanced. The plasma glucose-lowering effect of Hei-Shug-Pian
      was eliminated by blockade of opioid mu-receptors. Moreover, Hei-Shug-Pian
      treatment failed to lower plasma glucose in opioid mu-receptor knockout diabetic
      mice. The findings obtained in this study support the conclusion that Hei-Shug
      Pian lowers the plasma glucose concentrations of STZ-diabetic rats through
      activation of opioid mu-receptors of peripheral tissues, resulting in enhanced
      glucose utilization.

PMID- 16443341
TI  - Phytochemical and pharmacological study of roots and leaves of Guiera
      senegalensis J.F. Gmel (Combretaceae).
AB  - The chemical composition of total alkaloids from leaves and roots of Guiera
      senegalensis was investigated. Three beta-carboline alkaloids were purified: in
      addition to harman and tetrahydroharman, known in roots and leaves, harmalan
      (dihydroharman) was isolated for the first time from roots of Guiera
      senegalensis. Guieranone A, a naphthyl butenone, was also purified from leaves
      and roots. The in vitro antiplasmodial activity and the cytotoxicity of extracts
      and pure compounds were evaluated. Each total alkaloid extract and beta-carboline
      alkaloids presented an interesting antiplasmodial activity associated with a low
      cytotoxicity. Harmalan was less active than harman and tetrahydroharman.
      Guieranone A showed a strong antiplasmodial activity associated with a high
      cytotoxicity toward human monocytes. Its cytotoxicity was performed against two
      cancer cell lines and normal skin fibroblasts in order to study its anticancer
      potential: guieranone A presented a strong cytotoxicity against each cell
      strains. Finally, we evaluated the potent synergistic antimalarial interaction
      between Guiera senegalensis and two plants commonly associated in traditional
      remedies: Mitragyna inermis and Pavetta crassipes. Three associations evaluated
      were additive. A synergistic effect was shown between total alkaloids extracted
      from leaves of Guiera senegalensis and those of Mitragyna inermis. This result
      justified the traditional use of the plants in combination to treat malaria.

PMID- 16443342
TI  - In vivo anthelmintic activity of ginger against gastrointestinal nematodes of
      sheep.
AB  - This paper describes the anthelmintic activity of Zingiber officinale Roscoe
      (family Zingiberaceae) rhizome, commonly known as ginger, to justify its
      traditional use in veterinary medicine. Crude powder (CP) and crude aqueous
      extract (CAE) of dried ginger (1-3 g/kg) were administered to sheep naturally
      infected with mixed species of gastrointestinal nematodes. Both CP and CAE
      exhibited a dose- and a time-dependent anthelmintic effect with respective
      maximum reduction of 25.6% and 66.6% in eggs per gram (EPG) of faeces on day 10
      of post-treatment. Levamisole (7.5 mg/kg), a standard anthelmintic agent,
      exhibited 99.2% reduction in EPG. This study shows that ginger possesses in vivo
      anthelmintic activity in sheep thus justifying the age-old traditional use of
      this plant in helminth infestation.

PMID- 16443343
TI  - Bright and black blood imaging of the carotid bifurcation at 3.0T.
AB  - PURPOSE: The aim of this study was to evaluate our preliminary experience at 3.0
      T with imaging of the carotid bifurcation in healthy and atherosclerotic
      subjects. Application at 3.0 T is motivated by the signal-to-noise gain for
      improving spatial resolution and reducing signal averaging requirements.
      MATERIALS AND METHODS: We utilized a dual phased array coil and applied 2D, 3D
      time of flight (TOF) and turbo spin echo (TSE) sequences with comparison of two
      lumen signal suppression methods for black blood (BB) TSE imaging including
      double inversion preparation (DIR) and spatial presaturation pulses. The signal
      to-noise ratios (SNR) of healthy carotid vessel walls were compared in 2D and 3D
      BB TSE acquisitions. The bright and black blood multi-contrast exam was
      demonstrated for a complex carotid plaque. RESULTS: Contrast-to-noise (CNR)
      greater than 150 was achieved between the lumen and suppressed background for 3D
      TOF. For BB, both methods provided sufficient lumen signal suppression but slight
      residual flow artifacts remained at the bifurcation level. As expected 3D TSE
      images had higher SNR compared to 2D, but increased motion sensitivity is a
      significant issue for 3D at high field. For multi-contrast imaging of
      atherosclerotic plaque, fibrous, calcified and lipid components were resolved.
      The CNR ratio of fibrous (bright on PDW, T2W) and calcified (dark in T1W, T2W,
      PDW) plaque components was maximal in the T2W images. The 3D TOF angiogram
      indicating a 40% stenosis was complemented by 3D multi-planar reformat of BB
      images that displayed plaque extent. Detection of intimal thickening, the
      earliest change associated with atherosclerotic progression was observed in BB
      PDW images at 3.0 T. CONCLUSIONS: High SNR and CNR images have been demonstrated
      for the healthy and diseased carotid. Improvements in RF coils along with pulse
      sequence optimization, and evaluation of endogenous and exogenous contrast
      mechanisms will further enhance carotid imaging at 3.0T.

PMID- 16443344
TI  - Medullar fat influences texture analysis of trabecular microarchitecture on X-ray
      radiographs.
AB  - Alteration of trabecular architecture is a predictor of fracture risk in
      osteoporosis. Until now, microarchitecture analysis is difficult to evaluate in
      routine clinical practice for osteoporosis. Texture analysis on X-ray images has
      been advocated to be a suitable method to assess microarchitecture in bone
      diseases. The X-ray acquisition conditions have been often taken into
      consideration; however, the influence of anatomical conditions on texture
      parameters has received little interest. Because fat is a well-known problem with
      computed tomography and densitometry, we have designed a cadaver study to compare
      the influence of marrow lipids on numerous texture parameters. Twenty-one human
      distal radii were obtained, radiographed, and analyzed using a software that
      measures: heterogeneity, skeletonized parameters, run-lengths and fractal
      dimensions. Texture parameters were measured before, and after an extensive
      delipidation period lasting 3 weeks. Quality of the radiographs was improved
      after defatting. Delipidation had a very significant effect on measurements:
      afterwards defatting, the images were less blurred, and a better delineation of
      trabeculae and marrow cavities was obtained. This provoked an increase of
      parameters based on the grey level distribution but had no influence on
      parameters describing the reticulated honeycomb microarchitecture of the
      trabeculae (i.e., fractal dimension). Some parameters appeared anisotropy
      sensitive, due to the different constitution and size of the trabeculae. The fat
      content of bone marrow induces noise that can modify some texture parameters. One
      should take into account the fat content of the marrow when using texture
      analysis to compare patients with osteoporosis due to various etiologies.

PMID- 16443345
TI  - Pre-operative combined modality therapy in the management of locally advanced
      rectal cancer.
AB  - AIMS: To review the use of pre-operative combined modality therapy (CMT,
      chemotherapy with radiotherapy) in the management of resectable rectal cancer.
      METHODS: A systematic search was performed on pre-operative CMT and rectal
      cancer. Additional information was retrieved from hand searching the literature
      and from relevant congress proceedings. We addressed the following issues: Phase
      II studies of pre-operative CMT, pre-operative radiotherapy (RT) alone vs pre
      operative CMT, pre-operative vs post-operative CMT, functional outcome and
      pathologic downstaging after CMT, prediction and importance of complete response
      to CMT. RESULTS: Pre-operative CMT results in an average pathological complete
      response (pCR) rate of 18.5% in Phase II studies. Compared with pre-operative RT
      alone, the addition of CT significantly improves tumour response but not overall
      survival while acute toxicity increases and the effect on sphincter preservation
      is at present unclear. Pre-operative CMT has been proven to be superior to post
      operative CMT in a German multicenter randomized trial. The scarce available data
      suggest that the addition of CT might worsen anorectal function compared to pre
      operative RT alone. Although a significant pathological response is
      prognostically favourable, the clinical and imaging tools available at present do
      not allow to accurately predict pCR in clinical complete responders confirming
      the indication for surgery in this subgroup. CONCLUSIONS: Pre-operative CMT
      enhances tumour response and could therefore, have a role in patients with
      possibly invaded resection margins or low lying cancers, although both acute
      toxicity and anorectal function are worse compared to RT alone. The final results
      of ongoing randomized trials will more accurately establish the role of pre
      operative CMT in resectable rectal cancer patients.

PMID- 16443346
TI  - High-density comparative BAC mapping in the black muntjac (Muntiacus crinifrons):
      molecular cytogenetic dissection of the origin of MCR 1p+4 in the X1X2Y1Y2Y3 sex
      chromosome system.
AB  - The black muntjac (Muntiacus crinifrons, 2n = 8[female symbol]/9[male symbol]) is
      a critically endangered mammalian species that is confined to a narrow region of
      southeastern China. Male black muntjacs have an astonishing X1X2Y1Y2Y3 sex
      chromosome system, unparalleled in eutherian mammals, involving approximately
      half of the entire genome. A high-resolution comparative map between the black
      muntjac (M. crinifrons) and the Chinese muntjac (M. reevesi, 2n = 46) has been
      constructed based on the chromosomal localization of 304 clones from a genomic
      BAC (bacterial artificial chromosome) library of the Indian muntjac (M. muntjak
      vaginalis, 2n = 6[female symbol]/7[male symbol]). In addition to validating the
      chromosomal homologies between M. reevesi and M. crinifrons defined previously by
      chromosome painting, the comparative BAC map demonstrates that all tandem fusions
      that have occurred in the karyotypic evolution of M. crinifrons are centromere
      telomere fusions. The map also allows for a more detailed reconstruction of the
      chromosomal rearrangements leading to this unique and complex sex chromosome
      system. Furthermore, we have identified 46 BAC clones that could be used to study
      the molecular evolution of the unique sex chromosomes of the male black muntjacs.

PMID- 16443347
TI  - Neurocognitive and symptom correlates of daily problem-solving skills in
      schizophrenia.
AB  - Functional outcome for individuals with schizophrenia has been associated with
      cognitive impairment. Deficits in attention, memory, speed of information
      processing and problem-solving skills affect independent functioning, vocational
      performance, and interpersonal functioning. This study investigated the
      relationship between neurocognitive functioning, clinical symptoms and daily
      problem-solving skills in seriously and persistently ill persons. Thirty-eight
      inpatients and outpatients were administered a neurocognitive battery for
      attention, working memory, processing speed, perceptual organization, and
      executive functioning; and semi-structured clinical interviews using the BPRS and
      SANS. Estimates of daily problem-solving skills were obtained using the relevant
      factor subscale from the Independent Living Scales (ILS-PB). Daily problem
      solving skills were significantly correlated with negative symptoms, processing
      speed, verbal memory, and working memory scores. A regression model using an
      enter method suggests that working memory and negative symptoms are significant
      predictors of daily problem-solving skills and account for 73.2% of the variance.
      Further analyses demonstrate that daily problem-solving skills and negative
      symptoms were significantly different for inpatients and outpatients and
      significantly correlated with community status. The findings suggest the ILS-PB
      has utility as a proxy measure for assessing real-world functioning in
      schizophrenia.

PMID- 16443348
TI  - Does cognition predict community function only in schizophrenia?: a study of
      schizophrenia patients, bipolar affective disorder patients, and community
      control subjects.
AB  - Cognitive deficits predict functioning in schizophrenia; however, little is known
      as to whether the association is present in other mental disorders. If specific
      cognitive deficits uniquely predict functional impairment in schizophrenia the
      association of select aspects of brain dysfunction with daily living would
      suggest an intervention target and perhaps a means by which to improve the
      functioning of schizophrenia patients. The relationship of cognition and
      functioning was investigated in schizophrenia (n=39), bipolar affective disorder
      (n=27), and nonpsychiatric control (n=38) participants to determine whether the
      associations varied across groups. We examined verbal memory, verbal learning,
      verbal fluency, vigilance, executive functioning, symptomatology, and generalized
      cognitive functioning for associations with social function. Correlational
      analyses revealed particular cognitive domains (e.g., verbal memory) to be
      associated with social functioning in schizophrenia, bipolar, and control
      subjects; however generalized cognitive function and symptomatology were also
      associated with social functioning in patients. Multiple regression analyses
      revealed that in schizophrenia poor verbal memory predicted worse social
      functioning even after the effects of generalized cognitive dysfunction were
      considered. Verbal memory indices failed to account for variance in social
      function in bipolar patients and control subjects after consideration of
      generalized cognitive function. Bipolar patients with worse planning and problem
      solving tended to have worse social functioning. Therefore, unlike schizophrenia
      patients who may fail to process verbally mediated material, bipolar patients'
      difficulty with logical approaches to problems in daily living may have the
      greatest impact on their community function.

PMID- 16443349
TI  - Changes in functioning of rat submandibular salivary gland under streptozotocin
      induced diabetes are associated with alterations of Ca2+ signaling and Ca2+
      transporting pumps.
AB  - Xerostomia and pathological thirst are troublesome complications of diabetes
      mellitus associated with impaired functioning of salivary glands; however, their
      cellular mechanisms are not yet determined. Isolated acinar cells were loaded
      with Ca2+ indicators fura-2/AM for measuring cytosolic Ca2+ concentration
      ([Ca2+]i) or mag-fura-2/AM-inside the endoplasmic reticulum (ER). We found a
      dramatic decrease in pilocarpine-stimulated saliva flow, protein content and
      amylase activity in rats after 6 weeks of diabetes vs. healthy animals. This was
      accompanied with rise in resting [Ca2+]i and increased potency of acetylcholine
      (ACh) and carbachol (CCh) but not norepinephrine (NE) to induce [Ca2+]i
      transients in acinar cells from diabetic animals. However, [Ca2+]i transients
      mediated by Ca2+ release from ER stores (induced by application of either ACh,
      CCh, NE, or ionomycin in Ca2+-free extracellular medium) were decreased under
      diabetes. Application of inositol-1,4,5-trisphosphate led to smaller Ca2+ release
      from ER under the diabetes. Both plasmalemma and ER Ca2+-ATPases activity was
      reduced and the latter showed the increased affinity to ATP under the diabetes.
      We conclude that the diabetes caused impairment of salivary cells functions that,
      on the cellular level, associates with Ca2+ overload, increased Ca2+-mobilizing
      ability of muscarinic but not adrenergic receptors, decreased Ca2+-ATPases
      activity and ER Ca2+ content.

PMID- 16443350
TI  - Molecular chaperone alpha-crystallin prevents detrimental effects of
      neuroinflammation.
AB  - Silver nitrate administration stimulates immune activation, inflammation and
      deterioration in cell function. It is well established that hippocampal and
      cortical tissue are susceptible to degeneration in responses to insult such as
      oxidative stress or infection. This study was designed to investigate the
      prophylactic effect of alpha-crystallin, a major chaperone lens protein
      comprising of alpha-A and alpha-B subunits in inflammation induced mice. Mice
      were divided into three groups (n=6 in each), control, inflammation and alpha
      crystallin treated. Our result shows that alpha-crystallin pretreatment
      effectively diminished systemic inflammation induced glial fibrillary acidic
      protein (GFAP) and nuclear factor kappa B (NFkappaB) expression in the mice
      neocortex, reversed elevated intracellular calcium levels, acetylcholine esterase
      activity and depletion of glucose. Furthermore it also significantly prevented
      nitric oxide (P<0.05) and lipid peroxide production in the plasma, liver,
      neocortex and hippocampus of the inflammation-induced mice. In order to
      demonstrate the direct *OH and nitric oxide radical scavenging ability of alpha
      crystallin, an In vitro experiment using primary astrocyte culture subjected to
      lipopolysaccharide (LPS), a well-known inflammatory stimuli were also carried
      out. This study reiterates that alpha-crystallin therapy may serve as a potent
      pharmacological agent in neuroinflammation.

PMID- 16443351
TI  - Defining the heterochromatin localization and repression domains of SALL1.
AB  - SALL1 has been identified as one of four human homologues of the Drosophila
      region-specific homeotic gene spalt (sal), encoding zinc finger proteins of
      characteristic structure. Mutations of SALL1 on chromosome 16q12.1 cause Townes
      Brocks syndrome (TBS, OMIM 107480). We have shown previously that SALL1 acts as a
      strong transcriptional repressor in mammalian cells when fused to a heterologous
      DNA-binding domain. Here, we report that SALL1 contains two repression domains,
      one located at the extreme N-terminus of the protein and the other in the central
      region. SALL1 fragments with the central repression domain exhibited a punctate
      nuclear distribution pattern at pericentromeric heterochromatin foci in murine
      NIH-3T3 cells, suggesting an association between repression and heterochromatin
      localization. The implications of these findings for the pathogenesis of Townes
      Brocks syndrome are discussed.

PMID- 16443352
TI  - [Role of prescribing doctor in hyponatremic seizures of enuretic children on
      desmopressin].
AB  - Enuresis nocturna is regularly treated by desmopressin, a vasopressin analog. Its
      side effects, notably neurological, are fortunately rare. We comment on 5
      enuretic children on desmopressin who suffered from hyponatremic encephalopathy
      (natremia 115-127, median 117 mmol/l). RESULTS: Side effects appeared at
      therapeutic doses (10-40 mg/d intranasal). An excessive fluid intake at night was
      often noted, leading to a dilutional hyponatremia. This may be due to a lack of
      correct information to the parents. These children presented after a period of
      warning symptoms, such as headache, vomiting and altered consciousness. Parents
      could have sought earlier medical attention if they had been informed about these
      symptoms. CONCLUSION: In the absence of fluid restriction, severe hyponatremia
      can occur in enuretic children on desmopressin. It is therefore mandatory for the
      prescribing doctor to adequately inform patients and parents to limit fluids at
      night when desmopressin is used, and seek medical help quickly if any sign of
      intracranial hypertension appears.

PMID- 16443353
TI  - Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with
      mild allergic asthma.
AB  - Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily
      efficacy and potent anti-inflammatory activity. The aim of the study was to
      compare the effect of ciclesonide and fluticasone propionate on exhaled nitric
      oxide (FENO), pulmonary function, and other parameters used in clinical
      evaluation of patients with mild allergic asthma. The study indicates that
      ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster
      and stronger decrease of FENO in comparison with fluticasone (100 microg twice
      daily). In both groups of patients treated with ciclesonide, the highest decrease
      in FENO levels was observed after 2 weeks of treatment. In the group of patients
      treated with fluticasone, this maximum effect was not observed till 8 weeks. An
      improvement in spirometric indices was observed in all groups studied.
      Statistical differences between the groups were not found; however, there was a
      trend toward higher increase in the group receiving 160 microg of ciclesonide. In
      all groups studied we observed clinical improvement (asthmatic symptoms and
      consumption of rescue medication were reduced), but there were no significant
      differences between these groups. Our results indicate that ciclesonide, compared
      with fluticasone, has stronger anti-inflammatory activity in patients with mild
      allergic asthma.

PMID- 16443354
TI  - Retinoic acid and ascorbic acid act synergistically in inhibiting human breast
      cancer cell proliferation.
AB  - BACKGROUND: Breast cancer is an increasingly common malignancy. Several vitamins
      such as retinoic acid (RA), ascorbic acid (AA), vitamin D and vitamin E are known
      to prevent the development and progression of breast cancer. OBJECTIVE: We sought
      to determine whether RA and AA together (RA+AA) acted synergistically in blocking
      the proliferation of human breast cancer cells. To elucidate the mechanism by
      which RA+AA inhibited breast carcinoma proliferation, we then evaluated the gene
      expression profiles of the treated and untreated cells by radioactive cDNA
      microarray analysis. METHODS: We cultured the human breast cancer cell line MCF-7
      for 3 days with 100 nM RA and/or 1 mM AA, counted the cell numbers and harvested
      the total RNAs for cDNA microarray analysis. RESULTS: RA, AA and RA+AA reduced
      MCF-7 cell proliferation by 20.7%, 23.3% and 75.7% relative to the untreated cell
      proliferation, respectively. The synergistic ratio of RA and AA was 1.72. The MCF
      7 gene expression profiles showed that 29 genes were up-regulated and 38 genes
      were down-regulated after RA+AA treatment. The nature of these genes suggests
      that the mechanism by which RA and AA act synergistically in inhibiting human
      breast cancer cell proliferation may involve the expression of genes that induce
      differentiation and block proliferation, and the up-regulation of antioxidant
      enzymes and proteins involved in apoptosis, cell cycle regulation and DNA repair.
      CONCLUSION: Combined treatment with RA and AA inhibits the proliferation of human
      breast cancer cells by altering their gene expression related to antioxidation
      processes as well as the proliferation inhibitory pathway.

PMID- 16443355
TI  - Inhibition of advanced glycation end product formation on collagen by rutin and
      its metabolites.
AB  - Several lines of evidence suggest that rutin, flavonoid in fruits and vegetables,
      or one of its metabolites may effectively modulate advanced glycation end product
      (AGE) formation. Following ingestion, rutin forms metabolites that include 3,4
      dihydroxyphenylacetic acid (3,4-DHPAA), 3,4-dihydroxytoluene (3,4-DHT), m
      hydroxyphenylacetic acid (m-HPAA), 3-methoxy-4-hydroxyphenylacetic acid
      (homovanillic acid, HVA) and 3,5,7,3',5'-pentahydroxyflavonol (quercetin). We
      studied the effects of rutin and its metabolites on the formation of AGE
      biomarkers such as pentosidine, collagen-linked fluorescence, N(epsilon)
      carboxymethyllysine (CML) adducts, glucose autoxidation and collagen glycation,
      using an in vitro model where collagen I was incubated with glucose. Rutin
      metabolites containing vicinyl dihydroxyl groups, i.e., 3,4-DHT, 3,4-DHPAA and
      quercetin, inhibited the formation of pentosidine and fluorescent adducts,
      glucose autoxidation and glycation of collagen I in a dose-dependent manner,
      whereas non-vicinyl dihydroxyl group-containing metabolites, i.e., HVA and m
      HPAA, were much less effective. All five metabolites of rutin effectively
      inhibited CML formation. In contrast, during the initial stages of glycation and
      fluorescent AGE product accumulation, only vicinyl hydroxyl group-containing
      rutin metabolites were effective. These studies demonstrate that rutin and
      circulating metabolites of rutin can inhibit early glycation product formation,
      including both fluorescent and nonfluorescent AGEs induced by glucose glycation
      of collagen I in vitro. These effects likely contribute to the beneficial health
      effects associated with rutin consumption.

PMID- 16443356
TI  - Increased abundance of labile intracellular zinc during cell proliferation was
      due to increased retention of extracellular zinc in 3T3 cells.
AB  - Platelet-derived growth factor (PDGF)-, epidermal growth factor (EGF)- and
      insulin-like growth factor I (IGF-I)-stimulated cell proliferation in 3T3 cells
      was accompanied by increased abundance of labile intracellular pool of zinc
      (LIPZ). However, the origin and regulation of this cell proliferation-associated
      increase in the abundance of LIPZ are unknown. Cellular zinc homeostasis involves
      zinc transporters and metallothionein. The objectives of this study were to
      determine whether cell proliferation-associated increase in the abundance of LIPZ
      was a result of an increased zinc uptake and to assess the involvement of zinc
      transporters and metallothionein in this cell proliferation-associated increase
      in the abundance of LIPZ in 3T3 fibroblasts. Zinc transporters assessed included
      both zinc importer (Zip1) and zinc exporters (ZnT1, ZnT2 and ZnT4). Growth
      factors increased the abundance of LIPZ while total cellular zinc concentration
      remained unaffected, demonstrating that LIPZ was responsive to the increased
      needs for zinc during growth factor-stimulated cell proliferation. Growth factors
      also increased net zinc retention as indicated by higher 65zinc radioactivity and
      elevated mRNA levels of Zip1, ZnT1 and ZnT4. Although zinc is essential to cell
      proliferation, excessive cellular zinc accumulation causes cytotoxicity.
      Collectively, these observations suggest that increase in the abundance of LIPZ
      during growth factor-stimulated cell proliferation was due to increased net
      retention of extracellular zinc, which was apparently achieved through a
      coordinated up-regulation of the expression of transporters involved in both zinc
      influx and efflux to ensure adequate supply of zinc to sustain cell
      proliferation, yet to prevent potential zinc cytotoxicity in 3T3 cells.

PMID- 16443357
TI  - Mechanisms of action of green tea catechins, with a focus on ischemia-induced
      neurodegeneration.
AB  - Catechins are dietary polyphenolic compounds associated with a wide variety of
      beneficial health effects in vitro, in vivo and clinically. These therapeutic
      properties have long been attributed to the catechins' antioxidant and free
      radical scavenging effects. Emerging evidence has shown that catechins and their
      metabolites have many additional mechanisms of action by affecting numerous
      sites, potentiating endogenous antioxidants and eliciting dual actions during
      oxidative stress, ischemia and inflammation. Catechins have proven to modulate
      apoptosis at various points in the sequence, including altering expression of
      anti- and proapoptotic genes. Their anti-inflammatory effects are activated
      through a variety of different mechanisms, including modulation of nitric oxide
      synthase isoforms. Catechins' actions of attenuating oxidative stress and the
      inflammatory response may, in part, account for their confirmed neuroprotective
      capabilities following cerebral ischemia. The versatility of the mechanisms of
      action of catechins increases their therapeutic potential as interventions for
      numerous clinical disorders. However, more epidemiological and clinical studies
      need to be undertaken for their efficacy to be fully elucidated.

PMID- 16443358
TI  - Modulation of hepatic phase II phenol sulfotransferase and antioxidant status by
      phenolic acids in rats.
AB  - Phenolic acids have significant biological and pharmacological properties and
      some have demonstrated remarkable ability to alter sulfate conjugation. However,
      the modulatory effects of phenolic acids on phenol sulfotransferases (PSTs) in
      vivo have not been described. The present investigation evaluates the role of
      phenolic acid on the expression of PSTs in male Sprague-Dawley rat liver.
      According to the results, gentisic acid, gallic acid and p-coumaric acid in a
      dosage of 100 mg/kg of body weight for 14 consecutive days significantly
      increased P-form PST (PST-P) activity as compared with that of the control rats
      (P<.05), whereas the activity of M-form PST (PST-M) in rats that received gallic
      acid and p-coumaric acid were also significantly (P<.05) higher than in the
      control rats. Reverse transcriptase-polymerase chain reaction results indicated
      that the changes in both PST-P and PST-M mRNA levels by phenolic acids were
      similar to those noted in the enzyme activity levels. The plasma obtained from
      phenolic acid-administered rats had significantly (P<.05) increased oxygen
      radical absorbance capacity (ORAC(ROO*) values than that from control rats. In a
      bioavailability study, following oral administration of gallic acid and p
      coumaric acid, the phenolic acids were detected in the plasma, and the Cmax
      values after 2.0-h administration were 665+/-23 and 550+/-33 nmol/L,
      respectively. There was a significant correlation between the activity of both
      forms of PSTs and the antioxidant capacity of ORAC(ROO*) value by phenolic acids
      (r=.74, P<.05 and r=.77, P<.05). These data suggest that phenolic acids might
      alter sulfate conjugation and antioxidant capacity in living systems.

PMID- 16443359
TI  - Compendium of the antidiabetic effects of supranutritional selenate doses. In
      vivo and in vitro investigations with type II diabetic db/db mice.
AB  - In recent years, a number of investigations on the antidiabetic effects of
      supranutritional selenate doses have been carried out. Selenate (selenium
      oxidation state +VI) was shown to possess regulatory effects on glycolysis,
      gluconeogenesis and fatty acid metabolism, metabolic pathways which are disturbed
      in diabetic disorders. An enhanced phosphorylation of single components of the
      insulin signalling pathway could be shown to be one molecular mechanism
      responsible for the insulinomimetic properties of selenate. In type II diabetic
      animals, a reduction of insulin resistance could be shown as an outcome of
      selenate treatment. The present study with db/db mice was performed to
      investigate the antidiabetic mechanisms of selenate in type II diabetic animals.
      Twenty-one young adult female db/db mice were randomly assigned to three
      experimental groups (selenium deficient=0Se, selenite-treated group=SeIV and
      selenate-treated group=SeVI) with seven animals each. Mice of all groups were fed
      a selenium-deficient diet for 8 weeks. The animals of the groups SeIV and SeVI
      were supplemented with increasing amounts of sodium selenite or sodium selenate
      up to 35% of the LD50 in week 8 in addition to the diet by tube feeding. Selenate
      treatment reduced insulin resistance significantly and reduced the activity of
      liver cytosolic protein tyrosine phosphatases (PTPs) as negative regulators of
      insulin signalling by about 50%. In an in vitro inhibition test selenate
      (oxidation state +VI) per se did not inhibit PTP activity. In this test, however,
      selenium compounds of the oxidation state +IV were found to be the actual
      inhibitors of PTP activity. Selenate administration in vivo further led to
      characteristic changes in the selenium-dependent redox system, which could be
      mimicked in an in vitro assay and provided further evidence for the intermediary
      formation of SeIV metabolites. The expression of peroxisome proliferator
      activated receptor gamma (PPARgamma), another important factor in the context of
      insulin resistance and lipid metabolism, was significantly increased by selenate
      application. In particular, liver gluconeogenesis and lipid metabolism were
      influenced strongly by selenate treatment. In conclusion, our results showed that
      supranutritional selenate doses influenced two important mechanisms involved in
      insulin-resistant diabetes, namely, PTPs and PPARgamma, which, in turn, can be
      assumed as being responsible for the changes in intermediary metabolism, e.g.,
      gluconeogenesis and lipid metabolism. The initiation of these mechanisms thereby
      seems to be coupled to the intermediary formation of the selenium oxidation state
      +IV (selenite state) from selenate.

PMID- 16443360
TI  - Cyanidin attenuates PGE2 production and cyclooxygenase-2 expression in LNCaP
      human prostate cancer cells.
AB  - In the United States, the primary cancer in elderly men is prostate cancer (33%
      of newly diagnosed malignancies), but the prevalence is 75% lower in some
      Mediterranean countries. A possible explanation for the large difference in
      prostate cancer cases is that in Mediterranean countries the diet includes fish,
      olive oil and high amounts of nuts, fruits, vegetables, along with a regular
      intake of wine with meals several times per week. The LNCaP prostate cancer cells
      represent the nonaggressive androgen-dependent cell model that expresses moderate
      levels of cyclooxygenase-2 (COX-2). Epidemiological evidence indicates that
      polyphenolic compounds in diets are protective against cancer, and cyanidin and
      kaempferol are abundant in wine and plants. Therefore, the objective of the
      investigation was to determine the effects of cyanidin and kaempferol on
      prostaglandin E2 (PGE2) and COX-2 protein levels, and if peroxisome proliferator
      activated receptor gamma (PPARgamma) and nuclear factor kappaB (NFkappaB) are
      involved in the expression of COX-2 in prostate cancer cells. Cyanidin and
      kaempferol at 1 microM reduced the level of PGE2 in LNCaP cell cultures and also
      attenuated the effect of arachidonic acid on increasing the amount of PGE2.
      Cyanidin reduced the levels of COX-2 protein in a dose- and time-dependent
      fashion. PPARgamma mRNA levels were lower in cells treated after 24 h with
      kaempferol (0.1 and 1 microM) and cyanidin (1 microM). The reduction of COX-2
      mRNA by kaempferol and cyanidin may be mediated through the actions of NFkappaB
      and PPARgamma as nuclear factors that bind to the COX-2 gene promoter.

PMID- 16443361
TI  - Physical activity alters antioxidant status in exercising elderly subjects.
AB  - Nutritional adequacy and physical activity are two aspects of a health-promoting
      lifestyle. Not much is known about antioxidant nutrient requirements for
      exercising elderly (EE) subjects. The question of whether exercise training
      alters the status of antioxidant vitamins as well as trace elements in elderly
      subjects and fails to balance the age-related increase in oxidative stress is
      addressed in this study. There were 18 EE (68.1+/-3.1 years), 7 sedentary elderly
      (SE; 70.4+/-5.0 years), 17 exercising young (EY; 31.2+/-7.1 years) and 8
      sedentary young (SY; 27.1+/-5.8 years) subjects who completed 7-day food and
      activity records. Each subject's blood was sampled on Day 8. A similar selenium
      (Se) status but a higher erythrocyte glutathione peroxidase (GSH-Px) activity
      were found in EE subjects as compared with EY and SE subjects. Blood oxidized
      glutathione was higher and plasma total thiol was lower in EE subjects as
      compared with EY subjects. Mean vitamin C (167 vs. 106 mg/day), vitamin E (11.7
      vs. 8.3 mg/day) and beta-carotene (4 vs. 2.4 mg/day) intakes were higher in EE
      subjects as compared with EY subjects. However, EE subjects exhibited the lowest
      plasma carotenoid concentrations, especially in beta-carotene, which was not
      related to intakes. Despite high intakes of antioxidant micronutrients, no
      adaptive mechanism able to counteract the increased oxidative stress in aging was
      found in EE subjects. Results on GSH-Px activity illustrate that the nature of
      the regulation of this biomarker of Se status is different in response to
      training and aging. These data also strongly suggest specific antioxidant
      requirements for athletes with advancing age, with a special attention to
      carotenoids.

PMID- 16443362
TI  - Folding and binding: the conformational repertoire of proteins: folding,
      aggregation and structural recognition.

PMID- 16443363
TI  - Vacuum-assisted closure for the treatment of complex breast wounds.
AB  - Complex breast wounds are a constant problem for surgeons. Wound vacuum-assisted
      closure therapy (VAC) has been shown to be effective for a variety of complex
      wounds. Our goal was to evaluate our experience with the (VAC) device in the
      treatment of open breast wounds. We retrospectively identified 18 patients with
      complex breast wounds treated with the VAC. We analyzed the data regarding the
      nature and management of these wounds using the VAC device. Fifteen of 18
      patients were treated effectively using the VAC. Two patients required muscle
      flap coverage. One patient had the VAC dressing discontinued secondary to a
      denial by an insurance company for VAC in the home setting. VAC therapy is an
      effective treatment for complex wounds. Specifically, our experience shows it to
      be effective in the treatment of complex breast wounds. Utilization of VAC
      therapy should be considered for the management of these challenging wounds.

PMID- 16443365
TI  - Characterization of specific noncovalent complexes between guanidinium
      derivatives and single-stranded DNA by MALDI.
AB  - Noncovalently bound complexes between highly basic sites of 12 guanidinium
      compounds and single-stranded DNA were studied using matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry. 6-Aza-2-thiothymine (ATT) was
      used as the matrix in the presence of ammonium citrate, and spectra were recorded
      in the positive ion mode. Detailed control experiments confirmed unambiguously
      the high selectivity and specificity of the guanidinium moiety for phosphate
      groups of DNA. The results verify the binding stoichiometry and show preferential
      binding of hydrophobic binders (pyrene and anthracene guanidinium derivatives) to
      all sequences examined. In addition, we demonstrate that electrostatic
      noncovalent interactions are strengthened with phosphorothioate analogs of DNA.
      These results clearly highlight the structure-directing role of the self
      assembling organic species and strongly emphasize the significance of
      concentration, hydrophobicity, hydrogen-bonding, and pi-pi interactions of the
      artificial receptor in the formation of these noncovalent complexes. Because of
      the ability of DNA-binding compounds to influence gene expression, and therefore
      cell proliferation and differentiation, the interactions described above could be
      important in providing a better understanding of the mechanism of action of these
      noncovalent genetic regulators.

PMID- 16443364
TI  - Influence of crosslinker identity and position on gas-phase dissociation of Lys
      Lys crosslinked peptides.
AB  - A systematic study of the dissociation patterns of crosslinked peptides analyzed
      by tandem mass spectrometry is reported. A series of 11-mer peptides was designed
      around either a polyalanine or polyglycine scaffold with arginine at the C
      terminus. One or two lysine residues were included at various locations within
      the peptides to effect inter- or intra-molecular crosslinking, respectively.
      Crosslinked species were generated with four commonly used amine-specific
      chemical crosslinking reagents: disuccinimidyl suberate (DSS), disuccinimidyl
      tartarate (DST), dithiobis(succinimidylpropionate) (DSP), and disuccinimidyl
      glutarate (DSG). The influence of precursor charge state, location of crosslink,
      and specific crosslinking reagent on the MS/MS dissociation pattern was examined.
      Observed trends in the dissociation patterns obtained for these species will
      allow for improvements to software used in the automated interpretation of
      crosslinked peptide MS/MS data.

PMID- 16443366
TI  - An impulse-driven liquid-droplet deposition interface for combining LC with MALDI
      MS and MS/MS.
AB  - A simple and robust impulse-driven droplet deposition system was developed for
      off-line liquid chromatography matrix-assisted laser desorption ionization mass
      spectrometry (LC-MALDI MS). The system uses a solenoid operated with a pulsed
      voltage power supply to generate impulses that dislodge the hanging droplets from
      the LC outlet directly to a MALDI plate via a momentum transfer process. There is
      no contact between the LC outlet and the collection surface. The system is
      compatible with solvents of varying polarity and viscosity, and accommodates the
      use of hydrophobic and hydrophilic MALDI matrices. MALDI spots are produced on
      line with the separation, and do not require further processing before MS
      analysis. It is shown that high quality MALDI spectra from 5 fmol of pyro-Glu
      fibrinopeptide deposition after LC separation could be obtained using the device,
      indicating that there was no sample loss in the interface. To demonstrate the
      analytical performance of the system as a proteome analysis tool, a range of BSA
      digest concentrations covering about 3 orders of magnitude, from 5 fmol to 1
      pmol, were analyzed by LC-MALDI quadrupole time-of-flight MS, yielding 6 and 57%
      amino acid sequence coverage, respectively. In addition, a complex protein
      mixture of an E. coli cell extract was tryptically digested and analyzed by LC
      MALDI MS, resulting in the detection of a total of 409 unique peptides from 100
      fractions of 15-s intervals.

PMID- 16443367
TI  - Sources of artefacts in the electrospray ionization mass spectra of saturated
      diacylglycerophosphocholines: from condensed phase hydrolysis reactions through
      to gas phase intercluster reactions.
AB  - The mass spectra of diacylglycerophosphocholine phospholipids comprised of
      saturated fatty acids (1,2-dipentanoyl-sn-glycero-3-phosphocholine (D5PC); 1,2
      dihexanoyl-sn-glycero-3-phosphocholine (D6PC), and 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (D14PC)) are sensitive to the electrospray ionization (ESI)
      conditions. When fresh solutions of phospholipid in 10 mM ammonium acetate are
      subjected to ESI, protonated oligomeric clusters, [DxPCn + H]+ (x = 5, 6, and 14)
      are observed in the following different types of mass spectrometers: 3D
      quadrupole ion trap; linear ion trap, and triple quadrupole. The formation of the
      protonated cluster ions is not unique to the ion trap instruments, although they
      tend to be more abundant in these instruments. As the ESI solutions age, new ions
      are observed, which correspond to acid-catalyzed solution phase deacylation
      reactions. The collision induced dissociation fragmentation reactions of the
      oligomer cluster ions exhibit a distinct dependence on the cluster size, with the
      larger clusters (n > 2) simply fragmenting via the loss of lipid monomers. In
      contrast, the fragmentation of the dimeric cluster ion is unique, resulting in a
      number of additional reactions including covalent bond formation via
      intermolecular cluster SN2 reactions and SN2 transfer of a methyl group. The
      nature of the charge has a significant role in the formation of products via
      these intermolecular cluster reactions. Changing the head group to
      phosphoethanolamine "switches off" the SN2 reactions, while changing the cation
      from a proton to either a sodium or a potassium ion, diminishes the
      intermolecular reactions relative to monomer loss. Semi empirical PM3
      calculations on [D6PC2 + H]+ suggest that the SN2 reactions are thermodynamically
      favored over simple monomer loss. These results have important implications in
      the field of lipidomics.

PMID- 16443368
TI  - Photofading of ballpoint dyes studied on paper by LDI and MALDI MS.
AB  - The determination of the age of an ink entry from a questioned document is often
      a major problem and a controversial issue in forensic sciences. Therefore, it is
      important to understand the aging process of the different components found in
      ink. The aim of this work is to characterize the degradation processes of methyl
      violet and ethyl violet, two typical ballpoint dyes by using laser
      desorption/ionization (LDI) and matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry (MS), and to evaluate the possible application of the
      method to forensic examination of documents. The mass spectrometric methods were
      first tested and were found to be adequate for the purpose of this work.
      Moreover, it is possible to analyze the dye from a stroke directly from the paper
      (LDI-MS), so the sample preparation is minimized. The degradation of the dyes
      methyl violet and ethyl violet in strokes from a ballpoint pen was studied under
      laboratory conditions influenced by different factors such as light, wavelength
      of light, heat, and humidity. Then, strokes from the same ballpoint were aged
      naturally in the dark or under the influence of light over one year and then
      analyzed. The results show that the degradation of these dyes strongly depends on
      light fluence. Humidity also increases degradation, which can be explained by the
      basicity of the paper. The influence of heat on the degradation process was found
      to be rather weak. It was also observed that the dyes from the ink strokes did
      not show significant degradation after one year of storage in the dark. In
      conclusion, the storage conditions of a questioned document and the initial
      composition of the dyes in the ink have to be known for correct interpretation of
      the age of an ink entry. Measurements over longer periods of time are necessary
      to follow the degradation of dyes exempt from light exposure. LDI was found
      adequate and very useful for the analysis of ballpoint dyes directly from paper
      without further pretreatment.

PMID- 16443369
TI  - Multiple neutral loss monitoring (MNM): a multiplexed method for post
      translational modification screening.
AB  - Post-translational modifications of proteins are involved in determining the
      activity of proteins and are essential for proper protein function. Current mass
      spectrometric strategies require one to specify a particular type of
      modification, in some cases also a particular charge state of a protein or
      peptide that is to be studied before the actual analysis. Due to these
      requirements, most of the modifications on proteins are not considered in such an
      experiment and, thus, a series of similar analyses need to be performed to ensure
      a more extensive characterization. A novel scan strategy has been developed,
      multiple neutral loss monitoring (MNM), allowing for the comprehensive screening
      of post-translational modifications (PTM) on proteins that fragment as neutral
      losses in a mass spectrometer. MNM method parameters were determined by
      performing product ion scans on a number of modified peptides over a range of
      collision energies, providing neutral loss energy profiles and optimal collision
      energies (OCE) for each modification, supplying valuable information pertaining
      to the fragmentation of these modifications and the necessary parameters that
      would be required to obtain the best analysis. As the optimal collision energy
      was highly dependent on the type of modification and the charge state of the
      peptide, the MNM scan was operated with a collision energy gradient.
      Autocorrelation analyses identified the type of modification, and convolution
      mapping analyses identified the associated peptide. The MNM scan with the new
      collision energy parameters was successfully applied to a mixture of four
      modified peptides in a BSA digest. The implementation of this technique will
      allow for comprehensive screening of all modifications that fragment as neutral
      losses.

PMID- 16443370
TI  - The impact of CD4+CD25+ Treg on tumor specific CD8+ T cell cytotoxicity and
      cancer.
AB  - There is sufficient evidence to suggest that tumor growth elicits specific immune
      responses, including CD8(+) and CD4(+) T cell responses that may delay tumor
      growth and could potentially be harnessed to eradicate cancer. Nevertheless the
      frequent outcome of cancer is lethality associated with uncontrolled growth and
      dissemination of tumor cells. The failure of the immune response may be naturally
      programmed and related to a specific subpopulation of CD4(+)CD25(+) regulatory T
      cells, whose function is to protect us against autoimmunity. Recent
      investigations have shed light on the in vivo behavior and functions of these
      cells. It is becoming evident that a major impact of these cells is on the
      cytolytic action of specific CD8(+) T cells that target the tumor. Inhibition of
      cytotoxicity is dependent on TGF-beta signaling by the effector cells. Thus,
      targeting immune regulation may provide a promising approach to the immune
      therapy of cancer. This approach however could also have unexpected deleterious
      consequences, as surprising new observations indicate that regulatory T cells can
      also delay tumor growth by independent mechanisms that relate to their cross talk
      with the innate immune response to cancer.

PMID- 16443371
TI  - Myogenin-dependent nAChR clustering in aneural myotubes.
AB  - During development of the neuromuscular junction, nerve-derived agrin and the
      cell substrate laminin stimulate postsynaptic nAChR clustering. This clustering
      is dependent on activation of the tyrosine kinase, MuSK, which signals receptor
      clustering via a rapsyn-dependent mechanism. Myogenin is a muscle-specific
      transcription factor that controls myoblast differentiation and nAChR gene
      expression. Here, we used RNA interference to investigate if myogenin is also
      necessary for nAChR clustering. We find that myogenin expression is essential for
      robust nAChR clustering and cannot be compensated by the muscle regulatory
      factors MyoD, myf5, and MRF4. In addition, we show that clustering cannot be
      rescued in myogenin-depleted myotubes by simply overexpressing the essential
      clustering molecules MuSK, rapsyn, and nAChRs. These data suggest that myogenin
      controls the expression of molecules crucial to nAChR clustering in addition to
      its role in regulating nAChR gene expression.

PMID- 16443372
TI  - Transforming growth factor alpha attenuates the functional expression of AMPA
      receptors in cortical GABAergic neurons.
AB  - In the developing neocortex, brain-derived neurotrophic factor (BDNF) exerts a
      trophic activity to increase the expression and channel activity of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor
      subunits. Here, we demonstrate that the epidermal growth factor (EGF) receptor
      (ErbB1) ligands exert the opposite biological activity in cultured neocortical
      neurons. Subchronic stimulation of ErbB1 with transforming growth factor alpha
      (TGFalpha), EGF, or heparin-binding EGF (HB-EGF) down-regulated protein
      expression of the GluR1 AMPA receptor subunit in cultured neocortical neurons. In
      agreement, TGFalpha treatment decreased the Bmax of [3H] AMPA binding and GluR1
      mRNA levels. Immunocytochemistry revealed that the decrease in GluR1 was most
      pronounced in multipolar GABAergic neurons. To examine the physiological
      consequences, we recorded AMPA-evoked currents as well as miniature excitatory
      postsynaptic currents in morphologically identified putative GABAergic neurons in
      culture. Subchronic TGFalpha treatment decreased AMPA-triggered currents as well
      as the amplitude and frequency of miniature excitatory postsynaptic currents. An
      ErbB1 tyrosine kinase inhibitor, PD153035, inhibited the TGFalpha effect.
      Moreover, TGFalpha counteracted the neurotrophic activity of BDNF on AMPA
      receptor expression. Co-application of TGFalpha with BDNF blocked the BDNF
      triggered up-regulation of AMPA receptor expression and currents. These
      observations reveal a negative regulatory activity of the ErbB1 ligand, TGFalpha,
      which reduces the input sensitivity of cortical GABAergic neurons to attenuate
      their inhibitory function.

PMID- 16443374
TI  - Mapping cerebral blood flow during speech production in hereditary ataxia.
AB  - Dysarthria is a significant feature of the dominantly inherited spinocerebellar
      ataxias (SCA), but little is known about the patterns of brain activity
      associated with this disorder of motor speech control. Positron emission
      tomography (PET) was used to study regional cerebral blood flow during speech and
      rest in a group of 24 subjects with hereditary ataxia with mild-to-moderate
      dysarthria. These data were compared to the results obtained from a group of 13
      age-matched, normal speakers. In the ataxic subjects, speech rates during
      scanning were significantly slowed compared to normal speakers. Significant
      reductions in mean regional blood flow were found in the cerebellum but not in
      supratentorial regions in the ataxic subjects. Multiple linear regression was
      used to model speech rate from regional blood flow. Four regions were identified
      as having significant relationships with speech rate in the model: the left
      inferior frontal and transverse temporal regions, and the right inferior
      cerebellar region and caudate nucleus. The relationship between flow and rate was
      positive in the inferior frontal and cerebellar regions and negative in the
      caudate and the transverse temporal region. The ataxic model represents an
      elaboration of the relationship previously reported for normal speakers, likely
      reflecting both the effects of, and compensation for, cerebellar degeneration in
      motor speech control. Although the mean regional blood flow values presented a
      pattern of functional organization for motor speech control at odds with lesion
      data, the performance-based model was in agreement with clinical experience.
      Incorporating performance data in functional image analysis may be more revealing
      of system characteristics than simply examining mean blood flow values.

PMID- 16443373
TI  - Dehydroepiandrosterone sulfate (DHEAS) and risk for mortality among older
      Taiwanese.
AB  - PURPOSE: Studies based on Western populations showed a negative relationship
      between dehydroepiandrosterone sulfate (DHEAS) level and mortality, but no study
      examined this relationship in a non-Western country. We use data from a large,
      nationally representative sample (n = 963) of older Taiwanese to investigate
      whether serum DHEAS, predicts subsequent mortality during a 3-year period (2000
      to 2003) and whether an effect remains after controlling for baseline health
      status. METHODS: Baseline data collection included an individual interview,
      physical examination, and blood sample. A logit model is used to test the
      relationship between DHEAS level and risk for mortality, controlling for age,
      sex, and smoking status. RESULTS: Results show a marginally significant inverse
      relationship between DHEAS level and 3-year mortality risk. Participants with low
      DHEAS levels (<54.5 microg/dL) have 64% greater odds of dying than those with
      higher DHEAS levels (p < 0.06). After adjusting for various indicators of health
      status in 2000, the odds ratio (OR) for low DHEAS level remains substantial (OR =
      1.41), but not statistically significant. CONCLUSIONS: Although the analysis is
      limited by the short follow-up and small number of deaths, results are consistent
      with the notion that DHEAS level has a sizeable effect on mortality.

PMID- 16443375
TI  - Progression of putaminal degeneration in multiple system atrophy: a serial
      diffusion MR study.
AB  - By using diffusion-weighted imaging (DWI), we have recently shown abnormal
      diffusivity in the putamen of patients with the Parkinson variant of multiple
      system atrophy (MSA-P) which also correlated with disease severity, indicating
      the capability of putaminal diffusivity to serve as a marker for disease
      progression. We therefore performed a serial DWI study in 10 patients with MSA-P
      compared to 10 patients with Parkinson's disease (PD) to evaluate the dynamic
      evolution of diffusion properties in the basal ganglia including putamen, caudate
      nucleus and globus pallidum by means of the trace of the diffusion tensor
      (Trace(D)). For comparison, we have also analyzed the frequency and
      semiquantitative grading of MSA-P-related structural changes on conventional MRI
      including putaminal atrophy, lateral hyperintense margination of the putamen and
      putaminal signal hypointensity relative to the globus pallidum on T2 MR images.
      None of the Trace(D) values in the basal ganglia regions in the PD group changed
      significantly at follow-up compared to baseline. In MSA-P, a significant increase
      of the Trace(D) was found in the putamen, which correlated with motor progression
      as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). No
      significant change of any of the abnormal putaminal findings on routine MRI was
      obtained. We suggest that abnormal diffusivity in the putamen is sensitive to
      change over time in MSA-P and correlates with motor progression indicating that
      DWI may serve to monitor disease progression in MSA-P in an objective and
      quantitative manner.

PMID- 16443376
TI  - Auditory motion perception activates visual motion areas in early blind subjects.
AB  - We have previously shown that some visual motion areas can be specifically
      recruited by auditory motion processing in blindfolded sighted subjects [Poirier,
      C., Collignon, O., De Volder, A.G., Renier, L., Vanlierde, A., Tranduy, D.,
      Scheiber, C., 2005. Specific activation of V5 brain area by auditory motion
      processing: an fMRI study. Brain Res. Cogn. Brain Res. 25, 650-658]. The present
      fMRI study investigated whether auditory motion processing may recruit the same
      brain areas in early blind subjects. The task consisted of simultaneously
      determining both the nature of a sound stimulus (pure tone or complex sound) and
      the presence or absence of its movement. When a movement was present, blind
      subjects had to identify its direction. Auditory motion processing, as compared
      to static sound processing, activated the brain network of auditory and visual
      motion processing classically observed in sighted subjects. Accordingly, brain
      areas previously considered as specific to visual motion processing could be
      specifically recruited in blind people by motion stimuli presented through the
      auditory modality. This indicates that the occipital cortex of blind people could
      be organized in a modular way, as in sighted people. The similarity of these
      results with those we previously observed in sighted subjects suggests that
      occipital recruitment in blind people could be mediated by the same anatomical
      connections as in sighted subjects.

PMID- 16443377
TI  - Mu rhythm (de)synchronization and EEG single-trial classification of different
      motor imagery tasks.
AB  - We studied the reactivity of EEG rhythms (mu rhythms) in association with the
      imagination of right hand, left hand, foot, and tongue movement with 60 EEG
      electrodes in nine able-bodied subjects. During hand motor imagery, the hand mu
      rhythm blocked or desynchronized in all subjects, whereas an enhancement of the
      hand area mu rhythm was observed during foot or tongue motor imagery in the
      majority of the subjects. The frequency of the most reactive components was 11.7
      Hz +/- 0.4 (mean +/- SD). While the desynchronized components were broad banded
      and centered at 10.9 Hz +/- 0.9, the synchronized components were narrow banded
      and displayed higher frequencies at 12.0 Hz +/- 1.0. The discrimination between
      the four motor imagery tasks based on classification of single EEG trials
      improved when, in addition to event-related desynchronization (ERD), event
      related synchronization (ERS) patterns were induced in at least one or two tasks.
      This implies that such EEG phenomena may be utilized in a multi-class brain
      computer interface (BCI) operated simply by motor imagery.

PMID- 16443378
TI  - The role of adenosine in chondrocyte death in murine osteoarthritis and in a
      murine chondrocyte cell line.
AB  - OBJECTIVE: To investigate the role of adenosine in chondrocyte death in murine
      osteoarthritis (OA). METHODS: 5'-Nucleotidase (5'NT) generates adenosine. Enzyme
      activity was measured histochemically in normal murine and osteoarthritic STR/ort
      strain tibial cartilage. Adenosine-mediated cell death was investigated in MC615
      chondrocyte cultures. Adenosine receptors (ARs) were assessed by reverse
      transcriptase polymerase chain reaction (RT-PCR). Cellular uptake of [(3)H]
      adenosine was measured with or without the inhibitor, nitrobenzylthioinosine
      (NBTI). Cell death was assessed by cell counting and DNA laddering following
      selective receptor stimulation, or after modulating adenosine metabolism with
      adenosine deaminase (ADA) or adenosine kinase (AK) inhibitors [erythro-9-(2
      hydroxy-3-nonyl)adenine (EHNA) and Iodotubericidin (Itub)], or with homocysteine
      (HC). Markers of apoptosis were assessed by Western blotting. Cell studies were
      validated by incubating normal murine knee joints in a medium containing
      adenosine and metabolic inhibitors. Apoptotic chondrocytes were identified with
      the TUNEL reaction. RESULTS: 5'NT activity in STR/ort tibial cartilage increased
      with development of OA, especially close to OA lesions. Adenosine induced MC615
      cell death in the presence of ADA inhibition (100 microM EHNA), or 1mM HC, or
      both. Adenosine uptake, mediated by NBTI-sensitive adenosine transporters, was
      required for cell death. ARs were expressed (A2b>A2a>A1) but were not involved in
      mediating cell death. Cell death involved the activation of caspase-3 and DNA
      fragmentation and was prevented by inhibiting caspase activity. However, neither
      caspase-8 nor caspase-9 was detected. Adenosine+EHNA induced chondrocyte
      apoptosis in normal murine knee joints. CONCLUSION: Increased adenosine
      production may induce chondrocyte apoptosis and play a role in OA in STR/ort
      mice.

PMID- 16443379
TI  - Investigations in generalized osteoarthritis. Part 1: genetic study of Heberden's
      nodes.
AB  - OBJECTIVE: Until the current molecular genetic investigations, all available data
      concerning the genetic predisposition to Heberden's nodes are based on a single
      investigation by Stecher in the 1940s. There is controversy in the literature
      about the correlation between Heberden's nodes and generalized osteoarthritis
      (GOA). Our own epidemiological and clinical investigations support this
      correlation. Therefore, the question arises as to whether the remarkable
      inheritance described by Stecher is correct and whether Heberden's nodes can
      indeed be used as a genetic marker for GOA. METHODS: From our clinical trial on
      106 patients with Heberden's arthritis, we could identify 88 families from index
      cases. Altogether, we included 931 family members over a maximum of four
      generations. First of all, the genealogical trees of the families were
      established. Subsequently, we examined the patients' hands in respect of
      Heberden's nodes and completed the genealogical trees during home visits.
      RESULTS: In the 88 families analyzed, 152 patients with manifest Heberden's
      arthritis were listed (26 males, 126 females). The genealogical analysis of 156
      descendants (74 males, 82 females) of 93 patients with Heberden's nodes suggests
      autosomal dominant inheritance. In view of the age-related manifestation and age
      pattern of the descendants, we postulate a heterozygous manifestation for women
      (dominant gene action) and only a homozygous manifestation for men (recessive
      gene action). CONCLUSIONS: The genealogic analysis does not contrast with the
      quite remarkable inheritance described by Stecher but rather supports the
      hypothesis that manifestation is dominant in females and recessive in males. From
      our point of view, this heredity does not contradict latest genetic assays which
      show the possibility of genetic defects causing the hereditary osteoarthritis
      (OA).

PMID- 16443380
TI  - Iron(II) triggered conformational changes in Escherichia coli fur upon DNA
      binding: a study using molecular modeling.
AB  - In order to identify the Fur dimerization domain, a three-dimensional structure
      of the ferric uptake regulation protein from Escherichia coli (Fur EC) was
      determined using homology modeling and energy minimization. The Fur monomer
      consists of turn- helix -turn motif on the N-terminal domain, followed by another
      helix-turn-helix-turn motif, and two beta-strands separated by a turn which forms
      the wing. The C-terminal domain, separated by a long coil from the N-terminal,
      and consisting of two anti parallel beta strands, and a turn-helix-turn-helix
      turn motif. Residues in central domain were found to aid the dimer formation,
      residues 45-70 as evident in the calculated distances; this region is rich in
      hydrophobic residues. Most interactions occur between residues Val55, Leu53,
      Gln52, Glu49 and Tyr56 with closest contacts occurring at residues 49-56. These
      residues are part of an alpha-helix (alpha(4)) near the N-terminal. Upon raising
      the Fe(2+) concentration the binding of Fur dimer to DNA was enhanced, this was
      evident when, the Fur EC dimer was docked onto DNA "iron box" (it was found to
      bind the AT-rich region) and upon addition of Fe(2+) the helices near the N
      terminal bound to the major groove of the DNA. Addition of high Fe(2+)
      concentration triggered further conformational changes in the Fur dimer as was
      measured by distances between the two subunits, Fe(2+) mediated the Fur binding
      to DNA by attaching itself to the DNA. At the same time DNA changed conformation
      as was evident in the distortion in the backbone and the shrinking of major
      groove distance from 11.4 to 9.3A. Two major Fe(2+) sites were observed on the C
      terminal domain: site 1, the traditional Zn site, the cavity contains the
      residues Cys92, Cys95, Asp137, Asp141, Arg139, Glu 140, His 145 and His 143 at
      distances range from 1.3 to 2.2A. Site 2 enclave consists of His71, Ile50, Asn72,
      Gly97, Asp105 and Ala109 at very close proximity to Fe(2+). The closest contacts
      between Fur dimer and DNA at the AT-rich region were at residues Ala11, Gly12,
      Leu13, Pro18 and Arg19 mostly hydrophobic residues near the N-terminal domain.
      Close contacts repeated at His87, His88 and Arg112, and a third region near the C
      terminal at Asn137, Arg 139, Glu140, Asn141, His143, Asn141 and His145. Fur dimer
      has three major contact regions with DNA, the first on the N-terminal domain, a
      second smaller region at His87, His88 and Arg112 mediated by Fe(2+) ions, and a
      third region on the C-terminal domain consisting mainly of hydrophobic contacts
      and mediated by Fe(2+) ions at high concentration.

PMID- 16443381
TI  - Intra-adrenal interactions in fish: catecholamine stimulated cortisol release in
      sea bass (Dicentrarchus labrax L.).
AB  - The effect of the catecholamines, adrenaline and noradrenaline, on sea bass
      (Dicentrarchus labrax) and sea bream (Sparus auratus) interrenal cortisol
      production was studied in vitro using a dynamic superfusion system technique.
      Increasing concentrations of catecholamines (10(-6), 10(-8) and 10(-10) M)
      stimulated cortisol production in a dose-dependent manner, in sea bass only. The
      increase in cortisol production stimulated by adrenaline (10(-6) M) and
      noradrenaline (10(-6) M) was inhibited by sotalol (2 x 10(-5) M), but not by
      prazosin suggesting that catecholamines stimulate cortisol release through the
      beta-receptor subtype. To evaluate catecholamine-induced signal transduction in
      head kidney cells, measurements of cAMP production and [H3]myo-inositol
      incorporation were determined in head kidney cell suspensions. Adrenaline and
      noradrenaline (10(-6) M) increased cAMP production, but had no effect on total
      inositol phosphate accumulation. These results indicate that catecholamines
      released from the chromaffin cells within the interrenal tissue may act as a
      paracrine factor to stimulate interrenal steroidogenesis in the sea bass.

PMID- 16443382
TI  - Recovery from an activity-induced metabolic acidosis in the American alligator,
      Alligator mississippiensis.
AB  - The metabolic acidosis resulting from an intense exercise bout is large in
      crocodilians. Here we studied recovery from this pH perturbation in the American
      alligator. Metabolic rate, minute ventilation, arterial pH and gases, and strong
      ion concentration were measured for 10 h after exhaustion to elucidate the
      mechanisms and time course of recovery. Exhaustion resulted in a significant
      increase in lactate, metabolic rate, and ventilation, and a decrease in arterial
      PCO2), pH and bicarbonate. By 15 min after exhaustion, oxygen consumption
      returned to rest though carbon dioxide excretion remained elevated for 30 min.
      Arterial PO2), [Na+], and [K+], increased following exhaustion and recovered by
      30 min post-exercise. Minute ventilation, tidal volume, [Cl-], and respiratory
      exchange ratio returned to resting values by 1 h. The air convection requirement
      for oxygen was elevated between 15 and 60 min of recovery. Breathing frequency
      and pH returned to resting values by 2 h of recovery. Lactate levels remained
      elevated until 6 h post-exercise. Arterial PCO2) and [HCO3-] were depressed until
      8 h post-exercise. Compensation during recovery of acid-base balance was achieved
      by altering ventilation: following the initial metabolic acidosis and titration
      of bicarbonate, a relative hyperventilation prevented a further decrease in pH.

PMID- 16443383
TI  - Prevalence of selected infectious disease agents in cats from Arizona.
AB  - The objective of this study was to use polymerase chain reaction (PCR) assays to
      determine the prevalence of Ehrlichia species, Anaplasma phagocytophilum,
      Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum' and Bartonella
      species from feral and relinquished cats in Phoenix and Nogales, Arizona. DNA
      from one or more of the organisms was amplified from 31 of 112 blood samples
      (27.7%). DNA consistent with Bartonella clarridgeiae 15 (13.4%), Bartonella
      henselae 14 (12.5%), 'Candidatus M haemominutum' 9 (8.0%), and M haemofelis 5
      (4.5%) were detected. DNA of Ehrlichia species, Neorickettsia risticii, or A
      phagocytophilum was not amplified. Failure to amplify DNA of A phagocytophilum
      may relate to the absence of appropriate tick vectors. Failure to amplify
      Ehrlichia species DNA suggests that cats were not exposed, exposed but not
      infected, or infected but the DNA was not detected by the PCR assay used in this
      study. The Bartonella species and hemoplasma results suggest flea control should
      be maintained.

PMID- 16443384
TI  - Estimation of HRV spectrogram using multiple window methods focussing on the high
      frequency power.
AB  - In this paper, the results of different multiple window spectrum analysis methods
      are compared in the estimation of heart rate variability (HRV) power spectra, in
      the high frequency band (HF), around 0.25 Hz, related to respiratory sinus
      arrhythmia (RSA). The evaluation is performed by simulating different spectrum
      shapes and peak frequency locations and calculating the mean squared error of a
      frequency range close around the strongest spectral peak. The results show that
      it is preferable to use the Peak Matched Multiple Windows in most situations, but
      the Welch method and the Sinusoid Multiple Windows can be as reliable in certain
      aspects.

PMID- 16443385
TI  - Geographical patterns of end-stage renal disease incidence and risk factors in
      rural and urban areas of South Carolina.
AB  - To assess the geographical patterns of end-stage renal disease (ESRD) incidence
      and to identify the risk factors on the regional differences, the authors
      conducted an ecological study on incidence of ESRD and related risk factors in
      the 46 counties of South Carolina (SC). Age and gender adjusted, race specific
      incidence rates for each county in SC were calculated for the 11,346 ESRD
      patients of all ages who registered in the United States Renal Data Systems
      Network 6 from 1990 to 1999. County level exposure measures on population
      physician density, hospitalization rates of diabetes and hypertension, per capita
      income, percent college degree, and percent below poverty were evaluated. There
      was a significant increase in mean incidence rates of ESRD from 1990 to 1999 in
      SC (p<0.0001). The incidence rates were consistently higher in rural than in
      urban counties. Population physician density (relative risk (RR) 0.49, 95%
      confidence interval (95%Cl, 0.41-0.58) and rural residence (adjusted RR 1.66,
      95%Cl 1.59-1.74) were significantly associated with ESRD incidence. The strong
      relationship between ESRD and physician density suggests that access to adequate
      treatment of diabetes and hypertension is of paramount importance for ESRD
      prevention, and has important public policy implications.

PMID- 16443386
TI  - In beta-cells, mitochondria integrate and generate metabolic signals controlling
      insulin secretion.
AB  - Pancreatic beta-cells are unique neuroendocrine cells displaying the peculiar
      feature of responding to nutrients, principally glucose, as primary stimulus.
      This requires translation of a metabolic substrate into intracellular messengers
      recognized by the exocytotic machinery. Central to this signal transduction
      mechanism, mitochondria integrate and generate metabolic signals, thereby
      coupling glucose recognition to insulin secretion. In response to a glucose rise,
      nucleotides and metabolites are generated by mitochondria and participate,
      together with cytosolic calcium, to the stimulation of insulin exocytosis. This
      review describes the mitochondrion-dependent pathways of regulated insulin
      secretion. In particular, importance of cataplerotic and anaplerotic processes is
      discussed, with special attention to the mitochondrial enzyme glutamate
      dehydrogenase. Mitochondrial defects, such as mutations and reactive oxygen
      species production, are presented in the context of beta-cell failure in the
      course of type 2 diabetes.

PMID- 16443387
TI  - Evaluation of P53 and BAX gene expression and induction of apoptosis and necrosis
      by the cis-Pt(II) complex of 3-aminoflavone in comparison with cis
      diamminedichloroplatinum(II) (cis-DDP) in human lymphocytes.
AB  - Currently cis-diamminedichloroplatinum(II) (cis-DDP) is one of the most commonly
      applied compounds in chemotherapy of many types of cancer. However, a drawback is
      that its effectiveness presents with many side effects. Therefore, human normal
      lymphocytes were chosen as a model system to study cis-bis(3
      aminoflavone)dichloroplatinum(II) (the cis-Pt(II) complex of 3-aminoflavone) in
      comparison with cis-DDP. We examined the effect of both tested compounds on cell
      viability and induction of apoptosis and necrosis. Trypan blue and acridine
      orange/ethidium bromide staining were carried out, as well as quantitative
      analysis of the apoptotic signal of P53 and BAX induction caused by the cis
      Pt(II) complex of 3-aminoflavone in comparison with cis-DDP. cis-DDP induced a
      decrease of cell viability and led to a higher increase in necrosis and apoptosis
      than did the cis-Pt(II) complex of 3-aminoflavone. Moreover, at the molecular
      level cis-DDP increased P53 and BAX expression in comparison with the other
      tested compound. The cis-Pt(II) complex of 3-aminoflavone showed a weaker
      genotoxic effect in normal lymphocytes in comparison with cis-DDP, which was a
      stronger inducer of apoptosis and necrosis.

PMID- 16443388
TI  - Opposite effect of caveolin-1 in the metabolism of high-density and low-density
      lipoproteins.
AB  - Receptors of the scavenger class B family were reported to be localized in
      caveolae, the cell surface microdomains rich in free cholesterol and
      glycosphyngolipids, which are characterized by the presence of caveolin-1.
      Parenchymal hepatic and hepatoma HepG2 cells express very low levels of caveolin
      1. In the present study, stable transformants of HepG2 cells expressing caveolin
      1 were generated to address the effect of caveolin-1 on receptor activity.
      Compared to normal cells, these cells show higher (125)I-bovine serum albumin
      (BSA) uptake and cholesterol efflux, two indicators of functional caveolae. By
      immunoprecipitation, cell fractionation and confocal analyses, we found that
      caveolin-1 is well colocalized with the cluster of differentiation-36 (CD36) and
      the low-density lipoprotein (LDL) receptor (LDLr) but to a lesser extent with the
      scavenger receptor class B type I (SR-BI) in HepG2 cells expressing caveolin-1.
      However, caveolin-1 expression favors the dimerization of SR-BI. Two clones of
      cells expressing caveolin-1 were investigated for their lipoprotein metabolism
      activity. Compared to normal cells, these cells show a 71-144% increase in (125)I
      LDL degradation. The analysis of the cholesteryl esters (CE)-selective uptake (CE
      association minus protein association) revealed that the expression of caveolin-1
      in HepG2 cells decreases by 59%-73% LDL-CE selective uptake and increases high
      density lipoprotein (HDL)-CE selective uptake by 44%-66%. We conclude that the
      expression of caveolin-1 in HepG2 cells moves the balance of LDL degradation/CE
      selective uptake towards degradation and favors HDL-CE selective uptake. Thus, in
      the normal hepatic parenchymal situation where caveolin-1 is poorly expressed,
      LDL-CE selective uptake is the preferred pathway.

PMID- 16443389
TI  - The use of MRI in the evaluation of myopathy.
AB  - MRI has revolutionized the practice of many branches of medicine. However, within
      the field of Neurology MRI is used almost exclusively to examine the structure of
      portions of the central nervous system. Despite a limited number of objective
      tests, MRI remains an underutilized tool in the examination of the peripheral
      nervous system. This review will briefly discuss the limitations of current
      testing, and then summarize how the physics of MRI helps predict normal and
      abnormal findings in disease affecting skeletal muscle. The cardinal radiologic
      abnormalities affecting muscle (atrophy, hypertrophy, pseudohypertrophy, mass,
      and altered signal intensity) are reviewed. Special attention is given to how MRI
      can be utilized during the evaluation of such disorders. Finally, the roles of
      MRI as a prognostic tool and as a potential endpoint in long-term management of
      myopathy are evaluated.

PMID- 16443390
TI  - Twenty years research in cholinesterase biosensors: from basic research to
      practical applications.
AB  - Over the last decades, cholinesterase (ChE) biosensors have emerged as an ultra
      sensitive and rapid technique for toxicity analysis in environmental monitoring,
      food and quality control. These systems have the potential to complement or
      replace the classical analytical methods by simplifying or eliminating sample
      preparation protocols and making field testing easier and faster with significant
      decrease in costs per analysis. Over the years, engineering of more sensitive ChE
      enzymes, development of more reliable immobilization protocols and progress in
      the area of microelectronics could allow ChE biosensors to be competitive for
      field analysis and extend their applications to multianalyte screening,
      development of small, portable instrumentations for rapid toxicity testing, and
      detectors in chromatographic systems. In this paper, we will review the research
      efforts over the last 20 years in fabricating AChE biosensors and the recent
      trends and challenges encounter once the sensor is used outside research
      laboratory for in situ real sample applications. The review will discuss the
      generations of cholinesterase sensors with their advantages and limitations, the
      existing electrode configurations and fabrication techniques and their
      applications for toxicity monitoring. We will focus on low-cost electrochemical
      sensors and the approaches used for enzyme immobilization. Recent works for
      achieving high sensitivity and selectivity are also discussed.

PMID- 16443392
TI  - What about the carers?: Exploring the experience of caregivers in a chemotherapy
      day hospital setting.
AB  - Interest in the concerns of cancer patients' carers has been growing steadily
      over the last decade reflected in key cancer service policy documents [DOH, 1995.
      A Policy Framework for Commissioning Cancer Services (Calman-Hine Report).
      London, HMSO; DOH, 2002. The NHS Cancer Plan]. Despite this acknowledgement, it
      can be argued that less is known about carers' experience in the cancer treatment
      context. Carers can be defined as someone who shares the experience of cancer
      with the patient. The aim of this study was to explore the lived experience of
      caregivers in a chemotherapy day hospital and how this compared with their
      experience of inpatient care. Using a phenomenological approach, face-to-face
      interviews were conducted with a purposive sample of ten caregivers. Data were
      analysed using Polkinghorne's [1995. Narrative Knowing & the Human Sciences.
      University of New York Press, Albany] two stages of narrative analysis. The
      findings indicated that the caregivers experienced similar transitions to the
      patients with regards to health-illness transition and organisational
      transitions. The caregivers adopted various roles in the day hospital such as
      Companion 'being with' their relative, Protector 'keeping an eye'; Practical
      Caregiver and assuming an Advocate Role. The findings of this study are important
      for cancer nursing practice as health professionals need to acknowledge the role
      of carers in the chemotherapy day hospital setting and facilitate their
      involvement in care.

PMID- 16443391
TI  - Lead levels in blood and saliva in a low-income population of Detroit, Michigan.
AB  - The relationships between blood lead (PbB) and saliva lead (PbSa) concentrations
      and the determinants of PbB and PbSa status in 970 low-income adults in the city
      of Detroit, Michigan were explored. Average PbB and PbSa values in the sample
      population were found to be 2.7+/-0.1 microg/dl and 2.4+/-0.13 microg/l
      (equivalent to 0.24+/-0.13 microg/dl), respectively, and a weak but statistically
      significant association was found between the lead levels in the two types of
      body fluid samples. The average PbB level for men (4.0+/-0.56 microg/dl) was
      higher than that for women (2.7+/-0.11 microg/dl); other significant predictors
      of PbB included age, level of education, being employed, income level, the
      presence of peeling paint on the wall at home and smoking. There was no gender-
      or age-dependent difference in blood saliva values but statistically significant
      correlations were found between PbSa and level of education, employment, income
      level and smoking. Dental caries was severe in this population. Only 0.5% of the
      participants had no clinical signs of caries, over 80% had cavitated carious
      lesions (i.e., lesions that had progressed into dentin), and the number of lost
      teeth and carious lesions averaged 3.4 and 30, respectively. Weak but significant
      associations were found between PbB as well as PbSa and measures of dental caries
      in the study population. The positive associations are believed to be a
      reflection of the fact that the risk factors for dental caries, especially in low
      income populations of the US, overlap extensively with those of lead poisoning
      and may not have a causal significance.

PMID- 16443393
TI  - Utrophin upregulation for treating Duchenne or Becker muscular dystrophy: how
      close are we?
AB  - Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder for which
      there is currently no effective treatment. This disorder is caused by mutations
      or deletions in the gene encoding dystrophin that prevent expression of
      dystrophin at the sarcolemma. A promising pharmacological treatment for DMD aims
      to increase levels of utrophin, a homolog of dystrophin, in muscle fibers of
      affected patients to compensate for the absence of dystrophin. Here, we review
      recent developments in our understanding of the regulatory pathways that govern
      utrophin expression, and highlight studies that have used activators of these
      pathways to alleviate the dystrophic symptoms in DMD animal models. The results
      of these preclinical studies are promising and bring us closer to implementing
      appropriate utrophin-based drug therapies for DMD patients.

PMID- 16443394
TI  - Keratinocytes regain momentum as instigators of cutaneous inflammation.
AB  - The primary role of skin is to serve as a protective coat and epidermal
      keratinocytes are responsible for this barrier function. Besides providing
      structural support, keratinocytes can initiate inflammatory reactions, thereby
      enhancing healing of skin that follows barrier perturbation. In complex diseases
      such as psoriasis, in which both barrier function and cutaneous inflammation are
      dysregulated, it is unclear whether the primary pathogenic disturbance resides in
      keratinocytes or in immunocytes, which are commingled in psoriatic plaques.
      Researchers have turned to animal models of cutaneous inflammation to gain
      insights into the pathogenesis of psoriasis. A recent report in which the
      inducible epidermal deletion of Jun proteins in adult mice triggered inflammatory
      skin lesions and destructive arthritis has shifted momentum towards the
      keratinocyte as a key instigator of cutaneous inflammation. However, because this
      transgenic mouse model mimics only some features of psoriasis, further studies
      are required before the prevailing view of psoriasis as a fundamentally
      immunocyte-driven disease can be replaced by the notion that keratinocytes are
      the primary pathogenic cells in psoriasis.

PMID- 16443395
TI  - Access to modern contraception.
AB  - Access to modern contraception has become a recognized human right, improving the
      health and well-being of women, families and societies worldwide. However,
      contraceptive access remains uneven. Irregular contraceptive supply, limited
      numbers of service delivery points and specific geographic, economic,
      informational, psychosocial and administrative barriers (including medical
      barriers) undermine access in many settings. Widening the range of providers
      enabled to offer contraception can improve contraceptive access, particularly
      where resources are most scarce. International efforts to remove medical barriers
      include the World Health Organization's Medical Eligibility Criteria. Based on
      the best available evidence, these criteria provide guidance for weighing the
      risks and benefits of contraceptive choice among women with specific clinical
      conditions. Clinical job aids can also improve access. More research is needed to
      further elucidate the pathways for expanding contraceptive access. Further
      progress in removing medical barriers will depend on systems for improving
      provider education and promoting evidence-based contraceptive service delivery.

PMID- 16443396
TI  - Transduction of myogenic cells by retargeted dual high-capacity hybrid viral
      vectors: robust dystrophin synthesis in duchenne muscular dystrophy muscle cells.
AB  - Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene
      (DMD), making it amenable to gene- or cell-based therapies. Another possible
      treatment entails the combination of both principles by transplantation of
      autologous myogenic cells after their genetic complementation. This approach
      requires efficient and stable transduction of these cells with recombinant DMD.
      Recently, we generated a dual high-capacity (hc) adenovirus (Ad)-adeno-associated
      virus (AAV) hybrid vector (HV) that can deliver two full-length dystrophin
      encoding modules into target cells. We showed that HV transduction of human cells
      containing AAV Rep proteins leads to the insertion of foreign DNA into the AAVS1
      locus. Here, we improved HV entry into muscle cells from DMD patients. After
      having verified that these cells barely express the coxsackie B virus and Ad
      receptor (CAR), which constitutes the attachment molecule for Ad serotype 5 (Ad5)
      fibers, we equipped dual hcAd/AAV HV particles with Ad serotype 50 fiber domains
      to achieve CAR-independent uptake. These retargeted vectors complemented much
      more efficiently the genetic defect of dystrophin-defective myoblasts and
      myotubes than their isogenic counterparts with conventional Ad5 fibers.
      Importantly, the accumulation of beta-dystroglycan along the membranes of vector
      treated DMD myotubes indicated proper assembly of dystrophin-associated
      glycoprotein complexes.

PMID- 16443397
TI  - Fish mercury bioaccumulation as a function of feeding behavior and hydrological
      cycles of the Rio Negro, Amazon.
AB  - The acidic black waters of the Rio Negro are unimpacted by anthropogenic sources
      and yet, are characterized by fish containing relatively high Hg concentrations.
      Regular annual flooding alters the aquatic environment, thereby affecting fish
      feeding strategies. We studied the impact of annual flooding on fish-Hg
      bioaccumulation. Tucunares (Cychla spp, carnivorous), Peixe-cachorro (Hydrolycus
      scomberoides, carnivorous), Traira (Hoplias malabaricus, carnivorous), Piranha
      branca (Serrasalmus aff. eigenamanni, carnivorous), Piranha-preta (Serrasalmus
      rhombeus, carnivorous), Acara (Acarichthys heckellii, omnivorous), Aracu
      (Leporinus friderici, omnivorous), Orana-preta (Hemiodus unimaculatus,
      omnivorous), Sardinha (Triportheus elongatus, omnivorous), Branquinha
      (Potamorhina latior, detritivorous), Jaraqui-escama-fina (Semaprochilodus
      taeniurus, detritivorous), and Pacu-branco (Myleus torquatus, herbivorous) were
      studied during high (July) and low waters (February) and categorized by body
      mass. Regardless of hydrological period, ranges of total-Hg concentrations were
      higher for carnivorous than for omnivorous, detritivorous and herbivorous
      species. Some species (Traira, Sardinha, Peixe-cachorro, Piranha branca, Piranha
      preta) showed changes in feeding patterns as indicated by an inverse trend of Hg
      bioaccumulation with season. Species with similar trends of Hg bioaccumulation
      showed higher Hg concentrations during the flooded season (Aracu, Pacu branco and
      Orana preta) and some had lower Hg (Acara, Branquinha and Tucunares). Fish Hg
      concentration is species specific and reflects changes in feeding-behavior
      dominance brought by annual inundation.

PMID- 16443398
TI  - Redox kinetics of adriamycin adsorbed on the surface of graphite and mercury
      electrodes.
AB  - Kinetics of the surface redox reactions of adriamycin (doxorubicin hydrochloride)
      adsorbed on paraffin-impregnated graphite electrode (PIGE) and on mercury
      electrode is measured by square-wave voltammetry. In 0.9 mol/L KNO3 buffered to
      pH 4.65, the standard electrode reaction rate constants of the first
      quinone/hydroquinone redox couple (see Scheme 2) on PIGE and mercury are
      k(s1)=49+/-12 s(-1) and k(s1)=147+/-36 s(-1), respectively. Under the same
      conditions, the standard rate constant of the second redox couple on the PIGE is
      smaller than 4 s(-1) and the electron transfer coefficient of the reduction is
      alpha2=0.35.

PMID- 16443399
TI  - Three dimensional transport lattice model for describing action potentials in
      axons stimulated by external electrodes.
AB  - Conditions that stimulate action potentials in one or more nerves is of
      widespread interest. Axon and nerve models are usually based on two dimensional
      pre-specified lumped equivalents that assume where currents will flow. In
      contrast, here we illustrate creation of three dimensional (3D) system models
      with a transport lattice of interconnected local models for external and internal
      electrolyte and axon membrane. The transport lattice solves Laplace's equation in
      the extracellular medium and is coupled to the Hodgkin-Huxley model at local
      membrane sites. These space-filling models incorporate the geometric scale, which
      allows explicit representation of confined axons and external electrodes. The
      present results demonstrate feasibility of the basic approach. These models are
      spatially coarse and approximate, but can be straightforwardly improved. The
      transport lattice system models are modular and multiscale (spatial scales
      ranging from the membrane thickness of 5 nm to the axon segment length of 2 cm).

PMID- 16443400
TI  - Electrocatalytical properties of polymethylferrocenyl dendrimers and their
      applications in biosensing.
AB  - The electrochemical characterization of polymethylferrocenyl dendrimers deposited
      onto a platinum electrode and their applications as hydrogen peroxide and glucose
      sensor are described. The redox dendrimers consist of flexible
      poly(propileneimine) dendrimer cores functionalised with octamethylferrocenyl
      units. Amperometric biosensors for glucose were prepared by immobilization of
      glucose oxidase onto these modified electrodes. The influence of the dendrimer
      generation and the thickness of the dendrimer layer, the effect of the substrate
      concentration, and the interferences and reproducibility on the response of the
      sensors were investigated.

PMID- 16443401
TI  - Normal hypermutation in antibody genes from congenic mice defective for DNA
      polymerase iota.
AB  - Several low fidelity DNA polymerases participate in generating mutations in
      immunoglobulin genes. Polymerase eta is clearly involved in the process by
      causing substitutions of A:T base pairs, whereas polymerase iota has a
      controversial role. Although the frequency of mutations was decreased in the BL2
      cell line deficient for polymerase iota, hypermutation was normal in the 129
      strain of mice, which has a natural nonsense mutation in the Poli gene. It is
      possible that the mice compensated for the defect over time, or that polymerase
      eta substituted in the absence of polymerase iota. To examine polymerase iota in
      a genetically defined background, we backcrossed the 129 nonsense mutation to the
      C57BL/6 strain for six generations. Class switch recombination and hypermutation
      were studied in these mice and in congenic mice doubly deficient for both
      polymerases iota and eta. The absence of both polymerases did not affect
      production of IgG1, indicating that these enzymes are not involved in switch
      recombination. Poli(-/-F6) mice had the same types of nucleotide substitutions in
      variable genes as their C57BL/6 counterparts, and mice doubly deficient for
      polymerases iota and eta had the same mutational spectrum as Polh-/- mice. Thus,
      polymerase iota did not contribute to the mutational spectra, even in the absence
      of polymerase eta.

PMID- 16443402
TI  - Sensory transduction in cough-associated nerves.
AB  - Before a tussive stimulus in the airways can evoke a cough reflex it must first
      cause action potential discharge in cough-associated vagal sensory nerves. This
      is initiated by the stimulus first interacting with the receptors and ion
      channels in the terminal membrane of the sensory fiber in a manner that leads to
      membrane depolarization. If the stimulus-induced membrane depolarization,
      referred to as a generator potential, is of sufficient magnitude, action
      potentials are elicited that are then conducted to the central nervous system. If
      the action potentials are of sufficient number and frequency, a cough is evoked.
      The most common tussive stimuli include mechanical perturbations, anosmotic
      solutions, acidic solutions, and various chemical agents. The mechanisms
      underlying the transduction of most of these tussive stimuli into a generator
      potential are only partially understood. In general terms, chemical stimuli
      interact directly with receptors that are classified as either ligand gated ion
      channels or metabotropic receptors (e.g. G-protein coupled receptors). Ligand
      gated receptors are those in which the receptor protein also serves as the ion
      channel. The metabotropic receptors indirectly modulate the ion channels activity
      via various signal transduction schemes. Mechanical stimuli are thought to
      interact with mechanically gated ion channels, and acid can interact with acid
      sensing ion channels in addition to the capsaicin receptor TRPV1. In this
      overview some of the specific receptors and ion channels involved in the tussive
      stimulus-induced generator potentials in vagal afferent nerve terminals are
      discussed.

PMID- 16443403
TI  - Resting breathing frequency in aquatic mammals: a comparative analysis with
      terrestrial species.
AB  - Several species of aquatic mammals, while resting at the water surface, breathe
      with a low frequency (f). We asked if this was a general characteristic of
      mammals adapted to life in water. Measurements of f were obtained in 42 aquatic
      mammals of 19 species, during resting conditions. Data of additional 10 species
      were available from the literature. The allometric function for aquatic mammals
      was f=33W(-0.42) (f, breaths/min; W, kg; N=29, one data point per species, from
      six mammalian orders). This exponent was significantly different from that of the
      allometric curve of terrestrial mammals (W(-0.25)). The difference between
      aquatic and terrestrial species was small up to about 10kg, and widened with the
      increase in W. Out of several possibilities, it seems that the breath-holding
      response to favour buoyancy at the water surface could have contributed to the
      evolution of the low-f breathing, but a satisfactory explanation for the
      allometric pattern of f is still unavailable. In semi-aquatic mammals the low-f
      pattern observed at the water surface was maintained ashore, with no difference
      in the allometric function. As in the adult, also in the newborn of aquatic
      species f was low, compared to same-size neonates of terrestrial species. Hence,
      the low f has evolved to be part of the genetic makeup of aquatic mammals,
      retained when the animal is ashore, and already expressed at birth.

PMID- 16443404
TI  - Quantitative determination of 20-hydroxyecdysone in methanolic extract of twigs
      from Vitex polygama Cham.
AB  - 20-Hydroxyecdysone (20E) is effective in stimulating protein synthesis,
      therefore, it has been largely used as anabolic agent in several commercial
      formulas. Phytochemical study of methanolic extract of twigs from Vitex polygama,
      used in traditional Brazilian medicine as emenagogue, yielded a large quantity of
      20E. This finding led us to developing and validating a simple and reliable
      method to determine 20E in the surveyed extract. Chromatographic separation of
      20E was achieved on a phenyl-hexyl-based column using reversed elution mode.
      Extract was cleaned-up by solid phase extraction employing C(18) cartridge, and
      an absolute recovery of 97% was acquired. External standard and standard addition
      calibration graphs were obtained and good linearity was accomplished (r>0.999 for
      both curves). The limit of quantification and detection were determined. The
      results for accuracy fell within the -5 to +7% range.

PMID- 16443405
TI  - Reversible inactivation of alkaline phosphatase from Atlantic cod (Gadus morhua)
      in urea.
AB  - Alkaline phosphatase (AP) from Atlantic cod (Gadus morhua) is a zinc and
      magnesium containing homodimer that requires the oligomeric state for activity.
      Its kinetic properties are indicative of cold-adaptation. Here, the effect of
      urea on the structural stability was studied in order to correlate the activity
      with metal content, the microenvironment around tryptophan residues, and events
      at the subunit interface. At the lowest concentrations of urea, the first
      detected alteration in properties was an increase in the activity of the enzyme.
      This was followed by inactivation, and the release of half of the zinc content
      when the amount of urea reached levels of 2 M. Intrinsic tryptophan fluorescence
      and circular dichroism ellipticity changed in the range 2.5 to 8 M urea,
      signaling dimer dissociation, followed by one major monomer unfolding transition
      at 6-8 M urea as indicated by ANS fluorescence and KI fluorescence quenching.
      Gibbs free energy was estimated by the linear extrapolation method using a three
      state model as 8.6 kcal/mol for dimer stability and 11.6 kcal/mol for monomer
      unfolding giving a total of 31.8 kcal/mol. Dimer association had a very small
      ionic contribution. Dimers were stable in relatively high concentration of urea,
      whereas the immediate vicinity around the active site was vulnerable to low
      concentrations of urea. Thus, inactivation did not coincide with dimer
      dissociation, suggesting that the active site is the most dynamic part of the
      molecule and closest related to cold-adaptation of its enzymatic activity.

PMID- 16443406
TI  - Adherence and persistence: impact on outcomes and health care resources.
AB  - Non-adherence to and poor persistence with antiresorptive medication are
      significant problems in preventing adverse consequences of osteoporosis.
      Adherence rates for oral bisphosphonate therapy drop off dramatically during the
      first year of treatment and continue to decline thereafter. Inadequate adherence
      is associated with smaller decreases in rate of bone turnover, smaller bone
      mineral density (BMD) gains, and greater risk of fracture. Measures to improve
      patient adherence include improved physician/patient communication, close
      monitoring, and early intervention in declining adherence. Another approach is
      strengthening of patient commitment through reinforcement of the connection
      between treatment response and quality of life benefits. Use of biochemical
      markers of response or BMD measurements to illustrate response to patients may be
      useful in this regard. Simplification of treatment regimens would also be of
      considerable value in improving adherence and persistence.

PMID- 16443407
TI  - How can we improve our use of oral anticoagulants?

PMID- 16443408
TI  - Mitral regurgitation after myocardial infarction: a review.
AB  - Mitral regurgitation after myocardial infarction is the result of multifactorial
      processes involving local and global left ventricular remodeling. The prevalence
      of mitral regurgitation varies from 11% to 59%. Published studies differ greatly
      in design, inclusion criteria, duration of follow-up, and technique of mitral
      regurgitation assessment. However, they consistently indicate that mitral
      regurgitation after myocardial infarction carries an adverse prognosis with
      increased risk of death and heart failure independently of previously known
      indicators of risk after myocardial infarction. Mitral regurgitation is often
      clinically silent; therefore, it should be systematically evaluated by
      echocardiography. Standard color Doppler imaging is a highly sensitive method to
      detect even mild degrees of ischemic mitral regurgitation. One unique advantage
      of echocardiography is that it accurately quantifies the severity of mitral
      regurgitation by measuring the effective regurgitant orifice area and the
      regurgitant volume using Doppler methodology. Therefore, the evaluation should
      include precise quantification of the degree of mitral regurgitation to best
      appraise the ensuing risk. Current medical options rely chiefly on angiotensin
      converting enzyme-inhibitors and beta-blocker therapy, and surgical approaches
      offer future promise. Both categories of therapeutic approaches should be
      evaluated by randomized controlled trials.

PMID- 16443409
TI  - Selective serotonin reuptake inhibitors and increased bleeding risk: are we
      missing something?
AB  - PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) are first line agents to
      treat clinical depression. Although these medications exhibit a favorable safety
      profile, there are multiple case reports, registries, and uncontrolled studies
      suggesting that use of SSRIs might be associated in the increased risk of
      bleeding events. There is also emerging evidence that these side effects of SSRIs
      are due to blockade of serotonin reuptake in platelets and subsequent platelet
      dysfunction. METHODS: The analysis of evidence linking SSRIs with bleeding
      episodes to define the prevalence, specific clinical characteristics, and
      estimated risk when SSRIs are used in combination with antiplatelet agents or/and
      anticoagulants. RESULTS: There are over 120 MEDLINE-cited peer-reviewed research
      papers and more than 50000 Web pages devoted to SSRI-related bleeding events.
      CONCLUSION: Independently of the brand, use of SSRIs is indeed associated with
      increased bleeding risk. Although such complications are rare, their frequency is
      growing, and physicians should be aware of SSRI-induced hemorrhages, especially
      in patients with hereditary platelet defects, and those treated with antiplatelet
      agents. Prospective studies are urgently needed to determine whether SSRIs will
      yield additional bleeding risks when used long term concomitantly with aspirin or
      clopidogrel.

PMID- 16443411
TI  - Seeing red.

PMID- 16443410
TI  - The Valsalva maneuver: a bedside "biomarker" for heart failure.
AB  - Accurate assessment of volume status remains an important clinical goal in the
      management of patients with heart failure. Although physical examination can
      provide clues to volume status, its sensitivity and reproducibility are limited.
      Other noninvasive methods, such as measurement of natriuretic peptides or the use
      of impedance cardiography, are not well validated. The cardiovascular response to
      the Valsalva maneuver had been proposed as a simple, inexpensive bedside test for
      estimating filling pressures in patients with heart failure. Our objective was to
      summarize and critically evaluate the evidence for the use of the Valsalva
      maneuver in evaluating volume status in patients with heart failure. Studies have
      demonstrated a significant correlation between the cardiovascular response to the
      Valsalva maneuver and invasively measured ventricular filling pressures in
      patients with clinical heart failure. Although often overlooked in clinical
      training and practice, the cardiovascular response to the Valsalva maneuver is a
      potentially useful, noninvasive means of evaluating filling pressures in patients
      with heart failure.

PMID- 16443412
TI  - A ring-shaped eruption.

PMID- 16443413
TI  - Chest pain and a dominant R wave in lead V1 of the electrocardiograph.

PMID- 16443414
TI  - Magnetic resonance imaging of the heart in a patient with hypereosinophilic
      syndrome.

PMID- 16443415
TI  - Blood pressure usually considered normal is associated with an elevated risk of
      cardiovascular disease.
AB  - PURPOSE: Research on the risk of cardiovascular disease among individuals with
      prehypertension (blood pressure 120/80 to 139/89 mm Hg) is incomplete. Additional
      information among individuals with a high risk of cardiovascular disease
      complications may help to focus current and future efforts. SUBJECTS AND METHODS:
      We performed a prospective cohort analysis among 8960 middle-aged adults in the
      Atherosclerosis Risk in Communities (ARIC) study. The exposure variables were
      blood pressure levels: high normal blood pressure, systolic blood pressure 130
      139 mm Hg or diastolic blood pressure 85-89 mm Hg; and normal blood pressure,
      systolic blood pressure 120-129 mm Hg or diastolic blood pressure 80-84 mm Hg.
      The outcome was incident cardiovascular disease defined as fatal/nonfatal
      coronary heart disease, cardiac procedure, silent myocardial infarction, or
      ischemic stroke. Subgroup analysis was performed among blacks, diabetics,
      individuals aged 55-64 years, individuals with renal insufficiency, and among
      individuals with varying levels of low-density lipoprotein (LDL) cholesterol and
      body mass index (BMI). RESULTS: Compared with optimal blood pressure (systolic
      blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg), the relative
      risk (RR) of cardiovascular disease for high normal blood pressure was 2.33 (95%
      confidence interval [CI], 1.85-2.92), and RR for normal blood pressure was 1.81
      (1.47-2.22); among blacks: RR for high normal blood pressure was 3.29 (95% CI,
      1.68-6.45); among diabetics: RR for high normal blood pressure 4.10 (95% CI, 2.26
      7.46); age 55-64 years: RR for high normal blood pressure 2.41 (95% CI, 1.75
      3.30) among individuals with renal insufficiency: RR for high normal blood
      pressure was 1.90 (95% CI, 1.34-2.70); among individuals with BMI >30 kg/m2: RR
      for high normal blood pressure was 3.56 (95% CI, 1.99-6.35); and among
      individuals with LDL >160 mg/dL, RR for high normal blood pressure was 1.85 (95%
      CI, 1.26-2.72). CONCLUSIONS: Individuals with prehypertensive levels of blood
      pressure have an increased risk of developing cardiovascular disease relative to
      those with optimal levels. The association is pronounced among blacks, among
      individuals with diabetes mellitus, and among those with high BMI.

PMID- 16443416
TI  - Safety of expedited anticoagulation in patients undergoing transesophageal
      echocardiographic-guided cardioversion.
AB  - BACKGROUND: In patients undergoing transesophageal echocardiography-guided
      cardioversion, we evaluated the use and safety of an expedited in-hospital
      anticoagulation regimen that incorporates shorter-than-standard durations of
      precardioversion intravenous unfractionated heparin and postcardioversion
      bridging therapy with a low-molecular-weight heparin. METHODS: Adult patients who
      underwent successful transesophageal echocardiography-guided cardioversion for
      atrial fibrillation or atrial flutter between May 2000 and August 2003 were
      classified into 2 groups by duration of intravenous unfractionated heparin
      therapy (<24 h or > or =24 h) before transesophageal echocardiography and
      cardioversion. Safety end points evaluated included all-cause death, stroke or
      other thromboembolic events, and major bleeding complications within 1 month
      after successful cardioversion. RESULTS: The study population of 386 patients
      included 199 (52%) who received expedited intravenous unfractionated heparin (<24
      h; minimum duration, <4 h) and 193 patients (50%) who were discharged on low
      molecular-weight heparin therapy. The adverse event rates at 1-month follow-up
      were not significantly different between the 2 unfractionated heparin patient
      groups, and the rate of stroke among patients dismissed on low-molecular-weight
      heparin was less than 1%. No adverse events occurred among patients who received
      intravenous unfractionated heparin for less than 12 hours and who were dismissed
      on low-molecular-weight heparin bridging therapy. CONCLUSIONS: The use of an
      expedited heparin anticoagulation regimen in patients with atrial fibrillation or
      atrial flutter undergoing transesophageal echocardiography-guided cardioversion
      appears to be safe. Cardioversion can be performed as early as a few hours after
      initiation of intravenous unfractionated heparin, and bridging therapy with a low
      molecular-weight heparin can be used after cardioversion until the international
      normalized ratio is therapeutic.

PMID- 16443417
TI  - Medical versus surgical management of Staphylococcus aureus prosthetic valve
      endocarditis.
AB  - PURPOSE: The study's purpose was to identify prognostic factors associated with
      mortality in Staphylococcus aureus prosthetic valve endocarditis and to determine
      whether these factors influenced decisions to treat medically versus surgically.
      We also analyzed whether there was a subset of patients who were cured with
      medical therapy alone. SUBJECTS AND METHODS: A retrospective review of patients
      with S aureus prosthetic valve endocarditis was performed. Demographic and
      clinical data were collected from existing medical records. Severity of illness
      was classified using American Society of Anesthesiologists (ASA) score. Impact of
      treatment on in-hospital mortality was assessed using multiple logistic
      regression analysis. RESULTS: Fifty-five patients met the Duke criteria for
      definite S aureus prosthetic valve endocarditis. Twenty-three patients were
      treated medically, and 32 patients had surgical intervention. Overall mortality
      was 36% (28% in the surgical group and 48% in the medical group). ASA score IV (P
      < .001) and older age (P = .014) were significant risk factors of mortality.
      Patients with ASA score IV (P = .037) and multiple prosthetic valves (P = .013)
      were less likely to undergo surgery. Medically treated patients were older
      compared with those in the surgical group (median age 66 vs 55 years, P = .04).
      All 4 patients aged less than 50 years in the medically treated group survived.
      CONCLUSION: Mortality was generally higher in the medically treated patients with
      S aureus prosthetic valve endocarditis. Multivariable analysis showed that ASA
      class IV and bioprosthetic valves were independent predictors of mortality. A
      subset of medically treated patients characterized by age less than 50 years, ASA
      score III, and without cardiac, central nervous system, or systemic complications
      were cured without surgical intervention.

PMID- 16443418
TI  - Comparison of two hemofiltration protocols for prevention of contrast-induced
      nephropathy in high-risk patients.
AB  - PURPOSE: Contrast-induced nephropathy is a complication of contrast medium
      administration during diagnostic and interventional procedures, with important
      prognostic relevance. Patients with chronic kidney disease have a higher risk for
      contrast-induced nephropathy and poorer outcome. In patients with chronic kidney
      disease, hemofiltration reduces contrast-induced nephropathy incidence and
      improves long-term survival. We assessed the mechanisms involved in the
      prophylactic effect of hemofiltration and of the most effective hemofiltration
      protocol to prevent contrast-induced nephropathy in patients with chronic kidney
      disease. SUBJECTS AND METHODS: We randomized 92 patients with chronic kidney
      disease (creatinine clearance < or =30 mL/min) to three different prophylactic
      treatments: intravenous hydration with isotonic saline (1 mL x kg x h for 12
      hours before and after contrast exposure, control group; n = 30); intravenous
      hydration for 12 hours before contrast exposure, followed by hemofiltration for
      18 to 24 hours after contrast exposure (post-hemofiltration group; n = 31), and
      hemofiltration performed for 6 hours before and for 18 to 24 hours after contrast
      exposure (pre/post-hemofiltration group; n = 31). The incidence of contrast
      induced nephropathy (>25% increase in creatinine) and the in-hospital clinical
      course were compared in the three groups. RESULTS: Twelve patients (40%) in the
      control group, 8 patients (26%) in the post-hemofiltration group, and 1 patient
      (3%) in the pre/post-hemofiltration group experienced contrast-induced
      nephropathy (P = .0013); hemodialysis was required in 9 (30%), three (10%), and
      zero (0%) patients, respectively (P = .002). In-hospital mortality was 20%, 10%,
      and 0%, respectively (P = .03). CONCLUSIONS: Hemofiltration is an effective
      strategy for contrast-induced nephropathy prevention in patients with chronic
      kidney disease who are undergoing cardiovascular procedures. Pre-hemofiltration
      is required to obtain the full clinical benefit, suggesting that, among different
      mechanisms possibly involved, high-volume controlled hydration before contrast
      media exposure plays a major role.

PMID- 16443419
TI  - Pulmonary embolism as a cause of death in patients who died with cancer.
AB  - Little is known about the frequency of death from pulmonary embolism in patients
      who die with cancer. We investigated this on the basis of data from death
      certificates, as listed by the United States Bureau of the Census in the period
      1980-1998. Among patients with cancer who died over the 19-year period of study,
      pulmonary embolism was the listed cause of death in 0.21% (95% confidence
      interval, [CI] 0.21-0.22%). The frequency of death from pulmonary embolism in
      patients who died with cancer decreased from 0.39% in 1980 to 0.15% in 1998.
      Adjustment of the data for the frailty of the diagnosis of fatal pulmonary
      embolism based on death certificates indicated a likely range of 0.60% to 1.05%
      for the frequency of death from pulmonary embolism among patients who died with
      cancer in the period 1980-1998. In conclusion, with modern diagnostic,
      prophylactic, and therapeutic methods, death from pulmonary embolism in patients
      who died with cancer was 1% or less.

PMID- 16443420
TI  - The uninsured patient.

PMID- 16443421
TI  - What does minor elevation of C-reactive protein signify?
AB  - Reports of the predictive value of minor elevation of serum C-reactive protein
      (CRP) levels (between 3 and 10 mg/L) for atherosclerotic events have generated
      considerable interest, as well as a degree of controversy and confusion. CRP
      concentrations in this range are found in about one third of the American
      population. To better understand the mechanisms underlying minor elevation of
      CRP, we have surveyed its reported associations with a variety of states and
      conditions. It has become clear that even minimal environmental irritants and
      inflammatory stimuli elicit a minor CRP response. Minor CRP elevation has been
      found associated with a number of genetic polymorphisms, with membership in
      different demographic and socioeconomic groups, with a variety of dietary
      patterns and with many medical conditions that are not apparently inflammatory.
      Finally, minor CRP elevation bears negative prognostic implications for many
      conditions, particularly age-related diseases, and predicts mortality in both
      diseased and apparently healthy individuals. In sum, minor CRP elevation is
      associated with a great many diverse conditions, some of which are, or may prove
      to be, causal. Many of these reported associations imply a mild degree of tissue
      stress or injury, suggesting the hypothesis that the presence of distressed
      cells, rather than a resulting inflammatory response, is commonly the stimulus
      for CRP production.

PMID- 16443422
TI  - Current concepts in validity and reliability for psychometric instruments: theory
      and application.
AB  - Validity and reliability relate to the interpretation of scores from psychometric
      instruments (eg, symptom scales, questionnaires, education tests, and observer
      ratings) used in clinical practice, research, education, and administration.
      Emerging paradigms replace prior distinctions of face, content, and criterion
      validity with the unitary concept "construct validity," the degree to which a
      score can be interpreted as representing the intended underlying construct.
      Evidence to support the validity argument is collected from 5 sources: CONTENT:
      Do instrument items completely represent the construct? RESPONSE PROCESS: The
      relationship between the intended construct and the thought processes of subjects
      or observers. INTERNAL STRUCTURE: Acceptable reliability and factor structure.
      RELATIONS TO OTHER VARIABLES: Correlation with scores from another instrument
      assessing the same construct. CONSEQUENCES: Do scores really make a difference?
      Evidence should be sought from a variety of sources to support a given
      interpretation. Reliable scores are necessary, but not sufficient, for valid
      interpretation. Increased attention to the systematic collection of validity
      evidence for scores from psychometric instruments will improve assessments in
      research, patient care, and education.

PMID- 16443423
TI  - Progestins affect mechanism of estrogen-induced C-reactive protein stimulation.
AB  - PURPOSE: To determine whether the mechanisms of C-reactive protein production
      differ depending on the presence or absence of a progestin in the regimen.
      SUBJECTS AND METHODS: We examined data from the Postmenopausal Estrogen Progestin
      Intervention (PEPI) study, a 5-group (3 different combined estrogen-progestin
      regimens, conjugated equine estrogen-only, and placebo) randomized clinical
      trial. This substudy included 221 postmenopausal women assigned to active
      treatment groups who took at least 80% of pills and had stored plasma specimens
      available to assess 12-month changes in estrone, sex hormone binding globulin,
      interleukin (IL)-6, and C-reactive protein levels. RESULTS: All treatments
      resulted in increases in estrone, sex hormone binding globulin, and C-reactive
      protein at 12 months compared with baseline values. In all progestin-containing
      groups, 12-month change in IL-6 was positively correlated with 12-month change in
      C-reactive protein (r between 0.34 and 0.65, each P <.010). By contrast, in the
      conjugated equine estrogen-only group, 12-month change in IL-6 was negatively
      correlated with 12-month change in C-reactive protein (r value -0.31, P = .055).
      In adjusted models predicting 12-month C-reactive protein change, an interaction
      between change in IL-6 and treatment group was highly significant (P=.0008-P
      <.0001) for each of the progestin-containing groups compared with the conjugated
      equine estrogen-only group. In the conjugated equine estrogen-only group, the
      change in C-reactive protein per unit increase in IL-6 was -0.88, whereas in the
      progestin-containing groups it ranged from 1.46 to 2.85 (P <.0001 for each
      comparison with conjugated equine estrogen-only). CONCLUSION: Progestins in
      combination with conjugated equine estrogen potentiate the IL-6 (inflammatory)
      mediated stimulation of C-reactive protein. These findings support the hypothesis
      that progestins plus estrogen, not estrogen alone, generate C-reactive protein
      through an inflammatory mechanism.

PMID- 16443424
TI  - Disparities in the use of primary prevention and defibrillator therapy among
      blacks and women.
AB  - OBJECTIVES: This study determines whether there are racial or gender disparities
      in the use of implantable cardioverter-defibrillator therapy for primary
      prevention of sudden cardiac death. BACKGROUND: Primary prevention of sudden
      death with implantable cardioverter-defibrillator therapy has been shown to
      improve survival for high-risk patients with coronary artery disease and left
      ventricular dysfunction. METHODS: The Center for Medicare and Medicaid Services
      Medicare database from the year 2002 was used to identify patients who were
      potential candidates for implantable cardioverter-defibrillator therapy on the
      basis of a combination of International Classification of Diseases, Ninth
      Revision, Clinical Modification codes that reflected the presence of an ischemic
      cardiomyopathy. This cohort was analyzed to determine which patients received
      implantable cardioverter-defibrillator therapy during the same year. The clinical
      characteristics of the potential implantable cardioverter-defibrillator
      candidates were compared with those who actually received an implantable
      cardioverter-defibrillator. RESULTS: A total 132565 Medicare patients
      hospitalized during 2002 were identified as having an ischemic cardiomyopathy;
      10370 (8%) of these patients underwent implantable cardioverter-defibrillator
      implantation during the same year. The percentage of patients who underwent
      implantable cardioverter-defibrillator implantation was higher for men compared
      with women (10.2% vs 3.5%; P<.001) and whites compared with blacks (8.1 vs 5.4;
      P<.001). After multivariate analysis, age, gender, and race remained independent
      predictors of implantable cardioverter-defibrillator implantation. Women with an
      ischemic cardiomyopathy were 65% less likely to receive implantable cardioverter
      defibrillator therapy compared with men (P<.001), and black patients were 31%
      less likely to receive implantable cardioverter-defibrillator therapy compared
      with patients of other races (P < .001). CONCLUSIONS: Use of implantable
      cardioverter-defibrillator therapy for primary prevention of sudden death among
      the elderly population identified as having an ischemic cardiomyopathy was
      significantly lower among women compared with men, and among blacks compared with
      whites. Further exploration of gender and racial barriers to appropriate
      implantable cardioverter-defibrillator use for primary prevention is needed.

PMID- 16443425
TI  - Does methylphenidate reduce the symptoms of chronic fatigue syndrome?
AB  - PURPOSE: Chronic fatigue syndrome is a clinical entity consisting of prolonged
      and debilitating fatigue in which concentration disturbances are very frequent.
      Until now, no medical treatment has shown any efficacy. The objectives of this
      study were to investigate the short-term effects of methylphenidate, an
      amphetamine derivative, on fatigue, concentration disturbances, and quality of
      life. SUBJECTS AND METHODS: A double-blind randomized placebo-controlled
      crossover study was conducted in 60 patients who fulfilled the 1994 Centers for
      Disease Control criteria for chronic fatigue syndrome and had concentration
      difficulties. Patients were enrolled between March 2003 and March 2004 at the
      outpatient department of a university hospital referral center for chronic
      fatigue syndrome patients. Random assignment to 4 weeks treatment with
      methylphenidate 2 x 10 mg/day, followed by 4 weeks of placebo treatment, or 4
      weeks of placebo treatment, followed by methylphenidate treatment. Fatigue and
      concentration were measured with a Checklist Individual Strength (CIS) and a
      Visual Analogue Scale (VAS). RESULTS: Fatigue scores fell significantly during
      methylphenidate intake in comparison with baseline (mean difference: -0.7, P =
      .010 for VAS; mean difference: -11.8, P <.0001 for CIS) and in comparison with
      placebo (mean difference: -1.0, P = .001 for VAS; mean difference: -9.7, P <.0001
      for CIS). Concentration disturbances, measured with a VAS improved significantly
      under methylphenidate treatment compared with baseline (mean difference: -1.3, P
      <.0001) and compared with placebo (mean difference: -1.1, P <.0001). A clinical
      significant effect (> or =33% improvement or CIS < or =76) on fatigue was
      achieved in 17% of patients, who were considered responders; on concentration in
      22% of patients. CONCLUSIONS: Methylphenidate at a dose of 2 x 10 mg/day is
      significantly better than placebo in relieving fatigue and concentration
      disturbances in a minority of chronic fatigue syndrome patients. Further studies
      are needed to investigate the long-term effects of this treatment.

PMID- 16443426
TI  - Low insulin-like growth factor-II levels predict weight gain in normal weight
      subjects with type 2 diabetes.
AB  - PURPOSE: Insulin-like growth factor (IGF)-I and IGF-II are important in the
      regulation of metabolism and growth. We previously reported in normoglycemic
      individuals of normal weight that low circulating IGF-II predicts future weight
      gain. We subsequently investigated whether such relationships persisted in
      circumstances of type 2 diabetes. METHODS: In 224 subjects with type 2 diabetes
      we assessed the association between baseline IGF-II levels and risk of weight
      gain (>2.0 kg) at the 5-year follow-up. RESULTS: At follow-up, 90 participants
      (40.2%) gained more than 2.0 kg in body weight. For subjects (body mass index
      <26) at baseline, mean IGF-II levels were significantly lower in those who gained
      more than 2 kg in weight than in subjects of stable weight, 454 ng/mL (95%
      confidence interval 349-559) versus 620 ng/mL (534-705) (F=7.4, P=.01). For this
      subgroup low circulating IGF-II at baseline strongly correlated with weight gain
      (Spearman rho=-0.52, P <.001). With increasing weight, the relationship no longer
      prevailed. Logistic regression showed that for body mass index less than 26,
      individuals at baseline for each 100 ng/mL increase in baseline IGF-II there was
      a 47% decreased risk of gaining 2.0 kg or more in weight. Adjustment for
      treatment group did not materially alter this relationship. There was no
      difference in baseline IGF-II by treatment group. There was no difference between
      the group with weight gain and the group with stable weight in those who
      additionally received insulin or sulfonylurea treatment in the 5 years between
      the baseline visit and the follow-up. CONCLUSIONS: In subjects of normal weight
      with type 2 diabetes, baseline IGF-II concentration is inversely related to
      future weight gain, independent of treatment effect, strengthening the putative
      role for IGF-II in regulating fat mass. We propose that IGF-II measurement has
      potential utility in this group for targeting such individuals for early
      intervention.

PMID- 16443427
TI  - Evidence of brain damage after high-altitude climbing by means of magnetic
      resonance imaging.
AB  - PURPOSE: There are only anecdotal and small reports on brain systematic magnetic
      resonance imaging (MRI) studies in mountain climbers. The purpose of our work is
      to study the risk of brain lesions in mountain climbers by means of conventional
      MRI and magnetic resonance spectroscopy (MRS). METHODS: We recruited 35 climbers
      consecutively (12 were professional and 23 were amateur) in 4 expeditions without
      supplementary oxygen: 12 professionals and one amateur went up to Mt. Everest
      (8848 m), 8 amateurs to Mt. Aconcagua (6959 m), 7 amateurs to Mont Blanc (4810
      m), and 7 amateurs to Mt. Kilimanjaro (5895 m). The mean age was 33.8 years
      (range: 22-46). All of them underwent general medical examination, standard blood
      tests, and MRI of the brain after the expeditions. MRI also was carried out in a
      control group of 20 healthy subjects. Single-voxel MR spectroscopy was carried
      out in 14 amateur subjects after the expeditions and in 10 healthy controls. As
      outcome measures, we evaluated changes in the hematocrit value, presence of
      cerebral lesions on MRI, as well as atrophy and dilatation of Virchow-Robin
      spaces, and differences in the metabolite ratios obtained from brain MRS in
      comparison with controls. RESULTS: Only 1 in 13 of the Everest climbers had a
      normal MRI; the amateur showed frontal subcortical lesions, and the remainder had
      cortical atrophy and enlargement of Virchow-Robin spaces but no lesions. Among
      the remaining amateurs, 13 showed symptoms of high-altitude illness, 5 had
      subcortical irreversible lesions, and 10 had innumerable widened Virchow-Robin
      spaces. Conversely, we did not see any lesion in the control group. We found no
      significant differences in the metabolite ratios between climbers and controls.
      CONCLUSIONS: We conclude that there is enough evidence of brain damage after high
      altitude climbing; the amateur climbers seem to be at higher risk of suffering
      brain damage than professional climbers.

PMID- 16443429
TI  - Spontaneous cryptococcal peritonitis in patients with liver cirrhosis.

PMID- 16443430
TI  - Academic general internal medicine: past, present, future.

PMID- 16443428
TI  - Endemically acquired foodborne outbreak of enterotoxin-producing Escherichia coli
      serotype O169:H41.
AB  - PURPOSE: Enterotoxigenic Escherichia coli (ETEC) is traditionally recognized as a
      common cause of traveler's diarrhea, but is becoming a more frequent cause of
      foodborne disease outbreaks in the United States. It is important for public
      health practitioners and clinicians to be aware of ETEC as a domestic cause of
      gastroenteritis. We investigated a foodborne disease outbreak to understand the
      epidemiology of ETEC in this setting. METHODS: We conducted a cohort study of 63
      employees of Company A. A case was defined as an employee who experienced
      diarrhea or vomiting or fever and cramps after eating a catered meal at Company A
      from August 14th-15th. A standardized questionnaire was administered to cases and
      controls. RESULTS: Of 63 employees, 36 met the case definition (Attack Rate =
      57.1%). Diarrhea (94%) and cramps (74%) were common, whereas vomiting was not
      (3%). Mean duration of illness was 2.7 days. Coleslaw at the August 15th lunch
      was significantly associated with illness (Odds ratio = 4.4, 95% CI = 1.1-17).
      Stool specimens were positive for heat-stable enterotoxin-producing E. coli
      O169:H41. Contamination likely occurred at the point of service. CONCLUSIONS:
      This outbreak illustrates the changing epidemiology of enterotoxigenic E. coli
      and the importance for healthcare practitioners to consider ETEC as a potential
      cause of domestically acquired gastroenteritis.

PMID- 16443431
TI  - Rhabdomyolysis caused by an inherited metabolic disease: very long-chain acyl-CoA
      dehydrogenase deficiency.

PMID- 16443432
TI  - Acute pancreatitis in a patient with malnutrition due to major depressive
      disorder.

PMID- 16443433
TI  - Virchow's node and Horner's syndrome.

PMID- 16443434
TI  - A speculation about hypercholesterolemia in congenital analbuminemia.

PMID- 16443435
TI  - Persisting afebrile swelling of the lips and tongue: an unusual case of
      granulomatous glossitis.

PMID- 16443436
TI  - The clinical relevance of inhaled insulin in the diabetic lung.

PMID- 16443439
TI  - Antibiotics should be given only to patients with moderate-to-severe COPD.

PMID- 16443441
TI  - Letter to the editor regarding Davidson et al.

PMID- 16443442
TI  - Cardiovascular abnormalities in hyperthyroidism.

PMID- 16443443
TI  - Resident work hours: critique and caution.

PMID- 16443444
TI  - Fluoride levels in bottled teas.

PMID- 16443445
TI  - Letter regarding APM perspectives.

PMID- 16443447
TI  - Covariation and quantifier polarity: what determines causal attribution in
      vignettes?
AB  - Tests of causal attribution often use verbal vignettes, with covariation
      information provided through statements quantified with natural language
      expressions. The effect of covariation information has typically been taken to
      show that set size information affects attribution. However, recent research
      shows that quantifiers provide information about discourse focus as well as
      covariation information. In the attribution literature, quantifiers are used to
      depict covariation, but they confound quantity and focus. In four experiments, we
      show that focus explains all (Experiment 1) or some (Experiment 2-4) of the
      impact of covariation information on the attributions made, confirming the
      importance of the confound. Attribution experiments using vignettes that present
      covariation information with natural language quantifiers may overestimate the
      impact of set size information, and ignore the impact of quantifier-induced
      focus.

PMID- 16443446
TI  - Reading for repetition and reading for translation: do they involve the same
      processes?
AB  - Theories of translation differ in the role assigned to the reformulation process.
      One view, the "horizontal" approach, considers that translation involves on-line
      searches for matches between linguistic entries in the two languages involved
      [Gerver, D. (1976). Empirical studies of simultaneous interpretation: A review
      and a model. In R. W. Brislin (Ed.), Translation: Applications and research (pp.
      165-207). New York: Gardiner]. The second view, the "vertical" approach, assumes
      that on-line reformulation does not take place while reading: translation
      involves giving lexical expression to the meaning extracted after comprehension
      [Seleskovitch, D. (1976). INTERPRETATION: A psychological approach to
      translating. In R.W. Brislin (Ed.), Translation: Applications and research (pp.
      92-116). New York: Gardner]. In four experiments, translators or bilinguals read
      sentences for repetition or for translation. When participants read for
      translation, on-line and global comprehension was affected by lexical ambiguity
      and memory load (Experiment 1a and 1b). Furthermore, cognate words located at the
      final portion of the sentences facilitated performance (Experiment 2a and 2b).
      However, when participants were asked to understand and repeat the sentences,
      lexical ambiguity and the cognate status of the words did not have any effect.
      This pattern of results provides support for horizontal theories of translation.

PMID- 16443448
TI  - Principled and statistical connections in common sense conception.
AB  - Nominal concepts represent things as tokens of types. We report six experiments
      that investigate the nature of the relations we represent between the type of
      thing something is (e.g. DOG) and its other properties. The experiments provide
      evidence that we represent principled connections between the type of thing
      something is (e.g. DOG) and some of its properties (k-properties; e.g. having
      four legs for dogs), but not other properties (t-properties; e.g. being brown for
      dogs). Principled connections are different from logical, statistical, and causal
      connections. Principled connections, (i) license the expectation that tokens of
      the type will generally possess the k-property, (ii) license explanation of the
      presence of k-properties in tokens of a type by reference to the type of thing it
      is, and (iii) license normative expectations concerning the presence of the k
      property in tokens of the type. The experiments provide evidence for all three of
      these aspects of principled connections. The experiments also demonstrate that
      principled connections must be distinguished from merely strong statistical
      connections. We suggest that principled connections are one of the fundamental
      types of relations (in addition to logical, statistical, and causal relations) in
      terms of which our conceptual knowledge is structured. We argue that principled
      connections reveal a formal mode of understanding and explanation. This mode of
      understanding complements other modes of understanding that have been studied
      within the theory-based approach to conceptual representation. Finally, we
      suggest that kind representations are distinguished from representations of mere
      types by the representation of principled connections to k-properties.

PMID- 16443449
TI  - Cationic and perfluorinated polymeric pseudostationary phases for electrokinetic
      chromatography.
AB  - Separation selectivity in electrokinetic chromatography (EKC) is directly
      affected by the chemistry and solvent characteristics of the pseudostationary
      phase (PSP). The chemical selectivity of micellar PSPs has been previously
      demonstrated to vary significantly between anionic and cationic surfactants as
      well as between hydrocarbon and fluorocarbon surfactants. Polymeric PSPs have
      also been demonstrated to provide unique selectivity. In the current study, four
      cationic polymeric pseudo-stationary phases, two of which have perfluorinated
      pendant groups, are introduced and characterized as PSPs in EKC. Their
      performance and selectivity is compared to conventional micellar PSPs with
      similar structure. The solvation characteristics and selectivity of the four
      polymers most closely resemble those observed for cationic micelles. The polymers
      are all more cohesive and more polar than their hydrocarbon micellar
      counterparts. The fluorocarbon PSPs did show preferential interaction with
      fluorocarbon solutes, were somewhat more cohesive, and were stronger hydrogen
      bond donors. However, the presence of fluorocarbon moieties did not have as
      dramatic an effect on selectivity as was observed and published previously for
      fluorocarbon micelles. This may result from the selectivity being dominated by
      the presence of the cationic head groups or from the fluorocarbon character of
      the pendant groups being moderated by the presence of hydrocarbon functionality
      on the polymer backbones.

PMID- 16443450
TI  - Toward million-fold sensitivity enhancement by sweeping in capillary
      electrophoresis combined with thermal lens microscopic detection using an
      interface chip.
AB  - This paper reports a thermal lens microscope (TLM) detection coupled with
      capillary electrophoresis (CE) by using an interface chip (IFChip) to achieve
      highly sensitive detection with high reproducibility. Fused silica capillaries
      with an inner diameter of 50 microm were directly connected to a microchannel on
      the IFChip. In comparison with an on-capillary detection method in CE-TLM, ca. 10
      fold improvements in the reproducibility for peak height were obtained by using
      IFChips. The detection limit of an azo dye was estimated to be 3.6 x 10(-7)M (100
      ppb), which was above 100-times lower than that of conventional absorbance
      detection. Toward further improvement of the detectability for nonfluorescent
      compounds, on-line sample preconcentration by sweeping was applied to the CE-TLM
      using the IFChip. Due to the sweeping effect, 3900000-fold increase in the
      sensitivity was successfully achieved.

PMID- 16443451
TI  - On-line preconcentration of organic anions in capillary electrophoresis by solid
      phase extraction using latex-coated monolithic stationary phases.
AB  - Quaternary ammonium functionalised polymeric latex particles were coated onto the
      wall of a fused-silica capillary or onto a methacrylate monolithic bed
      synthesised inside the capillary in order to create ion-exchange stationary
      phases of varying ion-exchange capacity. These capillaries were coupled in-line
      to a separation capillary and used for the solid-phase extraction (SPE),
      preconcentration and subsequent separation of organic anions by capillary
      electrophoresis. A transient isotachophoretic gradient was used for the elution
      of bound analytes from the SPE phase using two modes of separation. The first
      comprised a low capacity SPE column combined with a fluoride/octanesulfonate
      discontinuous electrolyte system in which peak compression occurred at the
      isotachophoretic gradient front. The compressed anions were separated
      electrophoretically after elution from the SPE preconcentration phase and
      resolution was achieved by altering the pH of the electrolyte in which the
      separation was performed. In the second approach, a latex-coated monolithic SPE
      preconcentration stationary phase was used in combination with a
      fluoride/perchlorate electrolyte system, which allowed capillary
      electrochromatographic separation to occur behind the isotachophoretic gradient
      front. This method permitted the removal of weakly bound anions from the SPE
      phase, thereby establishing the possibility of sample clean-up. The effect of the
      nature of the strong electrolyte forming the isotachophoretic gradient on the
      separation and also on the preconcentration step was investigated. Capillary
      electrochromatography of inorganic and organic species performed on the latex
      coated monolithic methacrylate column highlighted the presence of mixed-mode
      interactions resulting from the incomplete coverage of latex particles onto the
      monolithic surface. Analyte preconcentration prior to separation resulted in
      compression of the analyte zone by a factor of 300. Improvement in the limit of
      detection of up to 10400 times could be achieved when performing the
      preconcentration step and the presented methods had limits of detection (S/N=3)
      ranging between 1.5 and 12 nM for the organic anions studied.

PMID- 16443452
TI  - Suppression of electroosmotic flow and its application to determination of
      electrophoretic mobilities in a poly(vinylpyrrolidone)-coated capillary.
AB  - A hydrophilic polymer, poly(vinylpyrrolidone) (PVP), was employed for suppressing
      the electroosmotic flow (EOF). A capillary was filled with aqueous PVP solution
      for coating the capillary wall with PVP; the PVP solution was then replaced by a
      migration buffer solution containing no PVP. Three types of PVP with different
      molecular weights were examined. The EOF was suppressed more effectively as the
      molecular weight of PVP increased. The EOF in the coated capillary was
      approximately 10-fold smaller than that of a bare capillary and was constant in
      the pH range of 6-8. The suppressed EOF was stable even when no PVP was added to
      the migration buffer. However, the EOF increased significantly when sodium
      dodecyl sulfate was added into the migration buffer. The method was applied for
      determining the electrophoretic mobilities of inorganic anions that have negative
      electrophoretic mobilities larger than the electroosmotic mobility of the bare
      capillary. A novel method for determining the electrophoretic mobilities was
      proposed based on the linear relationship between electric current and
      electrophoretic mobility. The electrophoretic mobility was proportional to the
      electric current. Therefore, the intercept of the regression equation represents
      the electrophoretic mobility at room temperature. The electrophoretic mobilities
      were in good agreement with the absolute electrophoretic mobilities.

PMID- 16443453
TI  - Analysis of glycoprotein-derived oligosaccharides in glycoproteins detected on
      two-dimensional gel by capillary electrophoresis using on-line concentration
      method.
AB  - Capillary electrophoresis (CE) is an effective tool to analyze carbohydrate
      mixture derived from glycoproteins with high resolution. However, CE has a
      disadvantage that a few nanoliters of a sample solution are injected to a narrow
      capillary. Therefore, we have to prepare a sample solution of high concentration
      for CE analysis. In the present study, we applied head column field-amplified
      sample stacking method to the analysis of N-linked oligosaccharides derived from
      glycoprotein separated by two-dimensional gel electrophoresis. Model studies
      demonstrated that we achieved 60-360 times concentration effect on the analysis
      of carbohydrate chains labeled with 3-aminobenzoic acid (3-AA). The method was
      applied to the analysis of N-linked oligosaccharides from glycoproteins separated
      and detected on PAGE gel. Heterogeneity of alpha1-acid glycoprotein (AGP), i.e.
      glycoforms, was examined by 2D-PAGE and N-linked oligosaccharides were released
      by in-gel digestion with PNGase F. The released oligosaccharides were derivatized
      with 3-AA and analyzed by CE. The results showed that glycoforms having lower pI
      values contained a larger amount of tetra- and tri-antennary oligosaccharides. In
      contrast, glycoforms having higher pI values contained bi-antennary
      oligosaccharides abundantly. The result clearly indicated that the spot of a
      glycoprotein glycoform detected by Coomassie brilliant blue staining on 2D-PAGE
      gel is sufficient for quantitative profiling of oligosaccharides.

PMID- 16443454
TI  - Negative mode sheathless capillary electrophoresis electrospray ionization-mass
      spectrometry for metabolite analysis of prokaryotes.
AB  - Capillary electrophoresis (CE) was coupled to negative mode electrospray
      ionisation-mass spectrometry (MS) for separation and detection of phosphorylated
      and acidic metabolites in extracts of prokaryotes. Unlike previous CE-MS systems
      for metabolite analysis, a sheathless interface was used to improve sensitivity.
      To accomplish this, the separation capillary was modified by creating a porous
      junction near the outlet where the electrospray voltage and cathodic voltage for
      CE were applied. The outlet of the capillary was pulled to a 5 microm inner
      diameter to form an electrospray emitter and had a frit fabricated near the exit
      to prevent clogging. During analysis pressure was applied at the inlet of the
      separation column to create sufficient flow towards the detector. Limits of
      detection for 19 metabolites in full scan mode ranged from 20 nM for ADP ribose
      to 2.5 microM for alpha-ketoglutarate for 40 nL injections. Extracts of
      Escherichia coli, strain DH5-alpha, were analyzed using this system. In full scan
      mode, 118 different metabolites were detected. Tandem mass spectrometry was also
      employed to attempt identification. Reproducible fragmentation of 19 parent peaks
      was found and 10 of these produced spectra that were consistent with
      identification obtained from matching to compounds in the MetaCyc database. These
      results demonstrate the utility of a sensitive CE-MS system for large scale
      metabolite detection in biological samples.

PMID- 16443455
TI  - Preparation of low flow-resistant methacrylate-based monolithic stationary phases
      of different hydrophobicity and the application to rapid reversed-phase liquid
      chromatographic separation of alkylbenzenes at high flow rate and elevated
      temperature.
AB  - Low flow-resistant alkyl methacrylate-based monolithic stationary phases of
      different hydrophobicity were constructed for reversed-phase capillary liquid
      chromatography by thermally initiated radical polymerization of respective
      methacrylate ester monomer with different alkyl chain (C2, C4, C6, C12, C18) and
      ethylene glycol dimethacrylate (EDMA) in a 250 microm i.d. fused silica
      capillary. The hydrophobicity was basically controlled by changing the length
      and/or the density of the alkyl-chain, while the composition and the ratio of
      porogenic solvent were adjusted to obtain highly permeable rigid monoliths with
      adequate column efficiency. Among the prepared monolithic stationary phases, C18
      methacrylate monoliths polymerized from a binary porogenic solvent of isoamyl
      alcohol and 1,4-buthandiol exhibited the most promising performance in terms of
      hydraulic resistance and column efficiency. The pressure drops of 20-cm long
      monolithic columns were below approximately 0.4 MPa at a normal linear velocity
      of 1mm/s (a flow rate of 3 microL/min), and the numbers of theoretical plates for
      alkylbenzenes mostly exceeded 3000 plates/20 cm. The produced monolithic columns
      had good mechanical strength for high pressure and temperature, and could be
      properly operated even at a temperature of 80 degrees C and at a pressure of at
      least 33 MPa. At 80 degrees C, the theoretical plate numbers reached 6000
      plates/20 cm because of the enhanced mass transfer. Due to the novel hydraulic
      resistance and mechanical strength, the separation time could be reduced 120-fold
      simply by raising the flow rate and column temperature.

PMID- 16443456
TI  - Separation of single-stranded DNAs using DNA conjugates having different
      migration properties in capillary electrophoresis.
AB  - A probe-regulated simultaneous separation (PRESS) using capillary electrophoresis
      (CE) was developed for separating single-stranded (ss) DNAs. We synthesized two
      DNA conjugate probes, -(5'-TGTGTGTGT-3')p-AAm(q)- and -(5'-GCCACCAGC-3')m-AAm(n)
      , by copolymerizing 5'-methacryloyl-modified ssDNA with acrylamide (AAm), and
      characterized them in detail. The two probes showed lower electrophoretic
      mobilities than 5'-methacryloyl-modified ssDNAs. Furthermore, -(5'-TGTGTGTGT-3')p
      AAm(q)- showed slightly faster electrophoretic mobility toward the anode than 
      (5'-GCCACCAGC-3')m-AAm(n)- due to its higher molar fraction of negatively-charged
      ssDNA. We successfully separated target ssDNAs having the same chain length by
      using two ssDNA conjugate probes that showed different electrophoretic
      mobilities, although the separation of these ssDNAs was difficult in conventional
      capillary electrophoresis systems.

PMID- 16443457
TI  - Investigation of chiral recognition mechanism on chicken alpha(1)-acid
      glycoprotein using separation system.
AB  - Chicken alpha1-acid glycoprotein (alpha1-AGP) consists of 183 amino acid residues
      and has only one Trp residue at the 26 position. In this study, the Trp26 residue
      was modified with 2-nitrophenylsulfenyl chloride and chiral separation of
      neutral, acidic and basic compounds was examined on chicken alpha1-AGP and Trp
      modified chicken alpha1-AGP columns. Chiral separation of propranolol, alprenolol
      and oxprenolol was lost on the Trp-modified chicken alpha1-AGP column, while
      chlorpheniramine, ketoprofen and benzoin were still enantioseparated on the Trp
      modified chicken alpha1-AGP column despite of lower enantioselectivity than that
      on the chicken alpha1-AGP column. These results suggest that the Trp26 residue
      could be responsible for chiral recognition of these compounds. Competition
      studies using N,N-dimethyl-n-octylamine (DMOA) as a competitor indicated that
      propranolol, alprenolol and oxprenolol competed with DMOA on a single binding
      site near the Trp26 region and that further bindings of chlorpheniramine,
      ketoprofen and benzoin occurred at the secondary binding site in a non
      competitive fashion with DMOA.

PMID- 16443458
TI  - Very high-pressure capillary liquid chromatography assisted by voltage.
AB  - Capillary liquid chromatography at moderately high pressures and capillary
      electrochromatography (CEC) have been combined to drive the mobile phase through
      capillary columns packed with small diameter particles. In a column packed with
      1.5 microm nonporous particles, linear velocities near 3mm/s were observed when
      combining inlet pressures of 690 bar (10,000 psi) and an applied voltage of 25
      kV. Optimum linear velocity for the column was achieved using a pressure-voltage
      combination of 350 bar (5000 psi) and 5 kV. Separation efficiencies at near
      optimum linear velocity agreed with those predicted by the van Deemter equation
      for liquid chromatography. Retention factors were observed to decrease under
      pressure-voltage combination as the voltage was increased; such a behavior has
      been attributed to Joule heating effects.

PMID- 16443459
TI  - On-line precolumn enrichment of bisphenol A using boronate column in microcolumn
      liquid chromatography.
AB  - The application of a boronate precolumn in the trace determination of 4,4'
      isopropylidenediphenol (bisphenol A or BPA) in aqueous solution was investigated
      by microcolumn liquid chromatography (LC). BPA was enriched by a precolumn packed
      with TSK(gel) boronate and it was then injected (back-flushed) into an ODS
      separation column. Comparing to a conventional syringe injection, a better peak
      shape was obtained via the boronate precolumn injection, and the calculated
      theoretical plate number improvement was approximately two folds. The relative
      standard deviations for the retention time, peak area and peak height were 0.12,
      3.0 and 1.8%, respectively. The system is linear (R2>0.99) within the working
      sample concentration and sample-volume ranges, and it presents a detection limit
      of 0.09 microg L(-1)(S/N=3) when a 0.2 mL sample was enriched. Recovery values of
      the proposed method were between 107 and 123%, and this method was applied
      satisfactorily to the determination of BPA in commercially available bottled
      drink samples. The boronate precolumn was proven to produce better sensitivity
      than that of an ODS or C30 precolumn as long as the enrichment of BPA in aqueous
      samples is concerned.

PMID- 16443460
TI  - Sensitive high-performance liquid chromatographic assay for D-amino-acid oxidase
      activity in mammalian tissues using a fluorescent non-natural substrate, 5-fluoro
      D-tryptophan.
AB  - A sensitive assay for D-amino-acid oxidase (DAO) activity in mammalian tissues
      has been established. D-Tryptophan (D-Trp) analogs were tested as substrates for
      DAO, and 5-fluoro-D-tryptophan (D-FTP) was found to be the best substrate. By the
      enzymatic reaction, D-FTP was converted to 5-fluoroindole-3-acetic acid (FIAA), a
      highly fluorescent product, and the product was determined by an RP-HPLC system
      with a fluorescence detector. The detection limit for purified DAO (from hog
      kidney) was 0.25 microU, and the within-day and day-to-day precisions of the
      assays were 4.6% (RSD, n=5), and 13.8% (RSD, 5 days), respectively. By the
      present method, the detailed distribution of DAO activity in the mouse brain was
      determined using individual animals for the first time, and significant
      activities were observed in the cerebellum, medulla oblongata and midbrain.
      Because sensitive DAO assay is frequently required in small tissues or in limited
      tissue regions, the present method is useful for various research studies
      concerning DAO and the related D-amino acids.

PMID- 16443461
TI  - In-needle extraction device designed for gas chromatographic analysis of volatile
      organic compounds.
AB  - A novel in-needle extraction device has been developed for the preconcentration
      of gaseous organic compounds prior to the determination in gas chromatography
      (GC). As the extraction medium, a copolymer of methacrylic acid and ethylene
      glycol dimethacrylate was synthesized. Based on the results in the preliminary
      experiments, the desorption conditions such as desorption temperature and time
      have been optimized along with the evaluation of the extraction efficiency. The
      storage performance of the needle extraction device was also studied. The results
      clearly demonstrated the excellent extraction performance for typical organic
      solvents and also suggested the future possibility such as in the applications
      for the analysis of working environments.

PMID- 16443462
TI  - Low-capacity channel designed for particle separation with controlled electric
      fields and evaluation of involved forces.
AB  - Electric field is one of the suitable physical fields applicable to particle
      separations. Although long rectangular channel is used for particle separation in
      usual electrical field flow fractionation (FFF), a short low-capacity channel can
      replace it if the field is precisely controlled. Several separation principles
      are proposed with this channel. The elution behavior of particles has revealed
      that the gravitational, diffusion, and hydrodynamic lift force (HLF) play
      important roles in the determination of the elution behavior of particles. The
      elution threshold voltage (V(th)) was defined and experimentally determined for
      various system configurations and particles. The electric force no longer
      overcomes the other forces, and particles are taken off the wall, when the
      applied voltage becomes lower than V(th). V(th) values have allowed us not only
      to estimate surface charge density of a particle but also to evaluate the
      hydrodynamic lift force against particle.

PMID- 16443464
TI  - AJO-DO rings in the new year. . . with changes.

PMID- 16443466
TI  - Distal jet versus pendulum appliance.

PMID- 16443467
TI  - Discriminant analysis of indiscriminate data.

PMID- 16443468
TI  - Outcome assessments.

PMID- 16443470
TI  - Transmigration of impacted and displaced maxillary canines: orientation of canine
      to the midpalatine suture.

PMID- 16443472
TI  - Smile esthetics: perception and comparison of treated and untreated smiles.
AB  - INTRODUCTION: Although orthodontic treatment is based primarily on occlusal
      relationships, greater attention is now paid to enhancing dentofacial
      characteristics to produce optimal facial esthetics. The purposes of this study
      were to compare smile esthetics among extraction and nonextraction patients and a
      control group, assess certain dentofacial characteristics in those groups, and
      discuss how these features relate to smile esthetics. METHODS: Panels of
      orthodontists, plastic surgeons, artists, general dentists, dental professionals,
      and parents used a 5-point scale to rate smiling photographs of 25 extraction, 25
      nonextraction, and 25 untreated control subjects. Dentofacial characteristics of
      the 3 groups were obtained from lateral cephalometric analyses, direct biometric
      measurements, and frontal photographs. Smile esthetics and differences among the
      3 groups were subjected to 1-way analysis of variance (ANOVA), and Pearson
      correlation coefficients were calculated to determine the relationship of the
      variables to the esthetic score. RESULTS: The mean esthetic scores for the
      extraction, nonextraction, and control groups were 3.15, 3.12, and 3.26,
      respectively. Visible dentition width relative to the smile width ratio and
      intercanine distance relative to smile width ratio were significantly different
      among the groups, with extraction patients showing a slightly wider dental arch
      relative to the soft tissue (P < .05). There was also a significant difference in
      the U1-SN angle among the groups (P < .05), and this variable showed a strong
      correlation with the esthetic score as did maxillary gingival display (P < .05).
      However, our study groups could not be differentiated in smile esthetics.

PMID- 16443473
TI  - Facial profile preferences of black women before and after orthodontic treatment.
AB  - INTRODUCTION: The purposes of this study were to determine (1) profile
      preferences of black female patients and (2) whether they can recognize their own
      profile images before and after orthodontic treatment. METHODS: Fifteen black
      orthodontists, 15 white orthodontists, and 15 black female patients were asked to
      indicate the images they considered most pleasing and to determine a zone of
      acceptability for 3 black female profiles. Raters used the PERCEPTOMETRICS
      computer program (Health Programs International, Wellesley, Mass). In addition,
      the 15 patients were asked to identify their most accurate pretreatment and
      posttreatment profile images. RESULTS: Analyses of variance showed that the white
      orthodontists preferred flatter profiles than the black women, who in turn
      preferred fuller profiles than the black orthodontists. Significant differences
      in lip position were detected for most pleasing and midpoint of acceptability
      among the 3 groups of judges, with no significant differences in any variables
      measured between treatments in rating the 3 images. No significant differences
      were detected for the magnitude of the zone of acceptability. All 15 black women
      recalled having fuller profiles than they actually did before treatment, but they
      could correctly identify their own profile images after treatment. CONCLUSIONS:
      The results of this study will facilitate the understanding of the physical bases
      of the esthetic judgments of black and white orthodontists and black female
      patients.

PMID- 16443474
TI  - Real-time balanced turbo field echo cine-magnetic resonance imaging evaluation of
      tongue movements during deglutition in subjects with anterior open bite.
AB  - INTRODUCTION: The aim of this study was to evaluate tongue movements in subjects
      with anterior dental open bites during deglutition by using real-time balanced
      turbo field echo cine-magnetic resonance imaging. METHODS: The study included 28
      subjects. Two groups were formed according to the presence of anterior open bite
      (at least 2 mm). The open-bite group (OBG) consisted of 18 patients (14 girls, 4
      boys) with a mean age of 14.5 +/- 2.7 years. The control group (CG) consisted of
      10 patients (5 girls, 5 boys) with a mean age of 14.5 +/- 2.6 years. We evaluated
      deglutition during 3 stages: oral (stage 1), pharyngeal (stage 2), and esophageal
      stage (3). RESULTS: Results indicated that (1) in the OBG, from stage 2 to stage
      3, the anterior portion of the tongue dorsum was elevated [corrected] whereas its
      midportion was lowered [corrected]; (2) in the CG, its posterior portion was
      lowered [corrected] from stage 2 to stage 3; (3) in the CG, the tongue tip was
      positioned more posteriorly [corrected] at stage 2 than at stage 1; (4) in the
      OBG, the tongue tip moved more anteriorly in all stages of deglutition than in
      the CG. CONCLUSIONS: Compensatory tongue functions occur in patients with
      anterior dental open bites. Dynamic MRI is a promising tool for evaluating
      swallowing patterns in these patients.

PMID- 16443475
TI  - A survey of hypodontia in Japanese orthodontic patients.
AB  - INTRODUCTION: The purpose of this retrospective study was to assess the
      prevalence and distribution of hypodontia in the permanent dentition, excluding
      the third molars, in a sample of Japanese orthodontic patients. METHODS:
      Orthopantomograms of 3358 Japanese orthodontic patients (1453 boys and 1905
      girls) between the ages of 5 and 15 years were examined for evidence of
      hypodontia. RESULTS: The prevalence of hypodontia was 8.5% (7.5% for boys, 9.3%
      for girls) with no statistically significant difference between the sexes. The
      average number of missing teeth per child was 2.4 (2.5 for boys, 2.4 for girls).
      Most (76.3%) children with hypodontia were missing either 1 or 2 teeth (77.1% for
      boys, 75.7% for girls). The prevalence of advanced hypodontia was 10.1% (11.0%
      for boys, 9.7% for girls). The most commonly missing teeth were the mandibular
      second premolars, followed by the mandibular and maxillary lateral incisors, and
      the maxillary second premolars; minor differences in the order of prevalence
      existed among groups of children classified by the number of missing teeth.
      Symmetrical hypodontia was predominant, and the most commonly symmetrical
      hypodontia was mandibular second premolar agenesis. No consistent finding was
      obtained as to which jaw had more missing teeth. The distribution of missing
      teeth was similar between the right and left sides of the dental arches in each
      group of children. Anterior tooth agenesis was predominant in children with minor
      hypodontia, and posterior tooth agenesis increased with hypodontia severity.
      CONCLUSIONS: The distinct characteristic of hypodontia in the Japanese population
      compared with other populations was a higher prevalence of both advanced
      hypodontia and mandibular lateral incisor agenesis in children with minor
      hypodontia.

PMID- 16443476
TI  - Changes in mandibular third molar angle and position after unilateral mandibular
      first molar extraction.
AB  - INTRODUCTION: Third molars often become impacted because of lack of space for
      their eruption. Because the third molars play an important role occlusally,
      premolars or second molars are sometimes extracted to create space. First molars
      are seldom extracted to create space, but they are occasionally extracted for
      other reasons, especially caries. The aim of this study was to investigate the
      spontaneous angular and positional changes in mandibular third molars when
      mandibular first molars are extracted. METHODS: The sample consisted of panoramic
      radiographs of 107 patients (age, 18-40 years; mean, 25.69 years) who had
      unilateral mandibular first-molar extractions (because of caries) before age 16.
      Ramus relationship, impaction depth, and angulation of third molars on the
      extraction and nonextraction sides were assessed. A chi-square test was performed
      to compare the differences. RESULTS: The prevalence of third molars at the
      anterior border of the mandibular ramus was significantly greater on the
      extraction side than on the nonextraction side (P < .001). Third molars were
      positioned more occlusally in the mandible on the nonextraction side than on the
      extraction side (P < .001). The prevalence of vertically angulated third molars
      was greater on the extraction side than on the nonextraction side (P < .001).
      CONCLUSIONS: Mandibular first-molar extraction increases the space for mandibular
      third-molar eruption and helps the third molars move into better positions. But
      early extraction can lead to uncontrolled tipping of adjacent teeth into the
      extraction space. Only third-molar angle and position were evaluated in this
      study; problems such as dental asymmetry, premature contacts, and uncontrolled
      tipping should be assessed in the future.

PMID- 16443477
TI  - Relationship between static natural head position and head position measured
      during walking.
AB  - INTRODUCTION: The aim of this project was to determine whether there is a
      statistically significant difference between the means of static and dynamic
      (measured during walking) measurements of head posture. METHODS: The sample
      consisted of 50 subjects, 25 women and 25 men, 20 to 25 years of age. None had a
      history of orthodontic treatment, head or neck injury, or nasal breathing
      problems, and none wore eyeglasses to correct vision. Static measurement of head
      position was recorded by using the self-balance position. Dynamic measurements of
      head position were made with an inclinometer device with the subject walking in a
      relaxed manner for 5 minutes. The data, measured in degrees, were stored in a
      pocket data logger. Recorded static and dynamic head posture data were
      transferred to a computer for analysis. The means of the measurements were
      statistically compared with the t test (alpha = .05). The mean walking head
      position was tipped forward relative to the mean static head position. RESULTS:
      The mean value of static position minus walking head position measurements was
      +4.60 degrees . The differences between the 2 recordings were statistically
      significant (P < .001). CONCLUSIONS: Static and walking head position
      measurements are not interchangeable. Therefore, it might be advisable to use the
      mean dynamic measurement of head position to represent natural head position for
      positioning when taking case records such as lateral and posteroanterior
      cephalograms, clinical extraoral photography, or 3-dimensional imaging.

PMID- 16443479
TI  - The effects of first- and second-order gable bends on forces and moments
      generated by triangular loops.
AB  - INTRODUCTION: Triangular loops are frequently used for space closure. Studies of
      this loop have focused on dimensional and in-plane (second-order) gable-bend
      influences on the generated forces and moments, but there have been no
      investigations into the effects of out-of-plane (first-order) gable bends. Both
      bends are generally needed to accomplish tooth translation. The primary purpose
      of this project was to ascertain whether first- and second-order bend effects
      were uncoupled. METHODS: Ninety triangular loops were divided into 9 groups with
      combinations of 0 degrees and 30 degrees first- and second-order gable bends in
      the anterior and posterior positions. Forces (F(x), F(y), F(z)) and moments
      (M(x), M(y), M(z)) generated along 3 mutually perpendicular axes-x (mesiodistal),
      y (occlusogingival), and z (buccolingual)-were measured, and moment/force ratios
      (M(z)/F(x), M(y)/F(x)) were calculated. Statistical comparisons were made between
      the 9 groups and between activation distances. The Sidak multiple-comparison
      adjustment method was used to control the overall confidence level at 95%.
      RESULTS: It was shown that the magnitude of M(z)/F(x) increased significantly
      with second-order gable bends but did not change with first-order bends. The
      opposite was found for M(y)/F(x). CONCLUSIONS: Thus, in triangular springs, first
      and second-order gable bends produce the desired effects without interfering
      with each other.

PMID- 16443478
TI  - Self-corrective T-loop design for differential space closure.
AB  - INTRODUCTION: The current approach to measuring T-loop force systems in patients
      requiring differential anchorage does not consider active unit angulations and
      steps during space closure. The angulations and steps during movement introduced
      by rotation can considerably modify the force system acting on the teeth.
      METHODS: In this study, geometric modifications were determined during controlled
      tipping of the 6 anterior teeth, where there was no movement of the posterior
      teeth, thus configuring a type A anchorage situation. RESULTS: An optimal beta
      titanium alloy 0.017 x 0.025-in T-loop spring was designed by using a simulation
      performed with LOOP software (dHAL Orthodontic Software, Athens, Greece) to allow
      compensation for anterior unit-position effect on the final force system. The
      force systems produced by this T-loop spring with and without geometric
      correction of the brackets have significant differences that should be considered
      in the segmented arch approach to space closure. CONCLUSIONS: The effects of
      steps, angles, and vertical forces were combined to produce an ideal T-loop
      design that would provide a more determinate force system. The effects and force
      systems are estimates based on simplified locations of the centers of resistance,
      assuming relatively constant behavior of the centers of rotation. These
      simplifications might differ slightly from what happens in vivo. The finite
      element method or an accurate spring tester capable of reproducing the geometric
      corrections should be used to ensure a precise force system.

PMID- 16443480
TI  - Effect of loading mode on bond strength of orthodontic brackets bonded with 2
      systems.
AB  - INTRODUCTION: A new orthodontic bracket bonding method or material invariably
      spawns bond strength studies examining the efficacy of the innovation. The
      primary purpose of this project was to ascertain whether the mode of in-vitro
      bracket debonding used in a study affects the measured bond strength. The
      secondary aim was to compare the bond strengths of 2 different bonding systems.
      METHODS: Flattened stainless steel orthodontic brackets were bonded to flattened
      bovine enamel with a resin composite bonding agent (Transbond XT, 3M Unitek,
      Monrovia, Calif). The enamel was prepared with traditional acid etching and
      priming (37% phosphoric acid gel and Transbond XT Primer, 3M Unitek) or a single
      step method (Transbond Plus, 3M Unitek) that combined etching and priming. Cement
      thickness was kept constant, and bonding was done under controlled temperature
      and humidity. Brackets were debonded in shear-peel, tension, or torsion. RESULTS:
      When tested in shear-peel mode, traditional etching and priming produced a
      stronger bond than the single-step self-etch system. When tested in tension, the
      traditional bond was weaker than the single-step bond, and when tested in
      torsion, the bond strengths were similar. CONCLUSIONS: Bond strength can vary
      depending on the method of testing. Claims of clinical efficacy might not be
      valid.

PMID- 16443481
TI  - Correction of a mandibular lateral incisor-canine transposition.
AB  - Early diagnosis of a transposition can simplify the orthodontic correction. In
      this report, we describe the orthodontic management of a patient with mandibular
      right lateral incisor and canine transposition. Nonextraction therapy was
      performed with removable multibracket appliances. Natural tooth order was
      attained, and a symmetric and functional Class I occlusion was achieved.

PMID- 16443482
TI  - Rapid prototyping: a new method of preparing trays for indirect bonding.
AB  - This article describes a new method of preparing trays for indirect bracket
      bonding. Computer-aided technology is used to design the individualized trays,
      which are then produced with a rapid prototyping procedure. Application in
      clinical practice and the advantages of time savings and accurate bracket
      placement are discussed.

PMID- 16443483
TI  - Litigation, legislation, and ethics. Models and the standard of care.

PMID- 16443488
TI  - Neuropathology of Alzheimer's disease.
AB  - In 1907, Alois Alzheimer described the presence of plaques and neurofibrillary
      tangles in a demented patient. Currently, Alzheimer's disease is known to be the
      most common cause of dementia in elderly patients. In this article, we summarize
      the most important neuropathologic features of Alzheimer's disease, including
      amyloid plaques, neurofibrillary tangles, neuronal loss, synaptic depletion,
      cerebral amyloid angiopathy, Hirano bodies, and granulovacuolar degeneration. We
      also review the history and application of Alzheimer's disease diagnostic
      criteria.

PMID- 16443487
TI  - Pathophysiology of Alzheimer's disease.
AB  - Tremendous progress has been made in understanding the processes of the
      Alzheimer's disease (AD) cascade, laying the groundwork for improvements in
      diagnosis and treatment. Advancement has been made in understanding the genetic
      basis of AD, with identification of causative genes for early-onset familial AD,
      and the role of the polymorphism of the APOE gene in the late-onset form of the
      disease. Understanding cerebral degeneration and accumulation of beta-amyloid has
      generated hopes for discovery of disease-modifying treatments. Progress is needed
      in understanding the mechanisms that link beta-amyloid accumulation and neuronal
      death. The next 5 years will be crucial in this respect.

PMID- 16443489
TI  - Clinical diagnosis and management of Alzheimer's disease.
AB  - The diagnosis of dementia of the Alzheimer's type is defined by criteria from the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and the
      National Institute of Neurologic, Communicative Disorders and Stroke-AD and
      Related Disorders Association. The latter divides diagnosis into definite,
      probable, and possible Alzheimer's disease (AD), with definitive diagnosis
      requiring pathologic confirmation. Both criteria require that other causes of
      dementia are excluded. A diagnosis of AD can be made with reasonably high
      accuracy using a combination of clinical criteria, neuropsychologic testing, and
      conventional CT and MR imaging. There is increasing emphasis on early
      recognition. Although current therapies produce a mild improvement in symptoms,
      there are several disease-modifying therapies on the horizon. This article
      reviews current standards in clinical diagnosis and management.

PMID- 16443490
TI  - A clinical perspective of mild cognitive impairment: what radiologists should
      know.
AB  - Mild cognitive impairment (MCI), a major risk factor for dementia, has an
      amnestic subtype that has a high probability of progressing to Alzheimer's
      disease. The rate of progression may be predicted by the severity of memory
      impairment at baseline, the severity of hippocampal atrophy, and, possibly, the
      presence of an epsilon4 allele of the apolipoprotein E gene. MCI can be diagnosed
      using purely clinical or a combination of clinical and neuropsychologic criteria.
      Treatment trials show no disease-modifying effect. The radiologists' role is to
      determine whether or not the hallmarks of degenerative and vascular disease of
      the brain are present, aiding in the diagnosis of the cause of MCI.

PMID- 16443491
TI  - The role of conventional MR and CT in the work-up of dementia patients.
AB  - Neuroimaging can play an important role in distinguishing one form of dementia
      from another. Advanced imaging techniques continue to provide greater insight
      into the underlying pathologic processes in patients who have dementia.
      Conventional MRI and CT, however, can contribute useful information when
      interpreting radiologists are familiar with the patterns of volume loss and
      signal or density changes that are characteristic of various forms of dementia.

PMID- 16443492
TI  - The role of quantitative structural imaging in the early diagnosis of Alzheimer's
      disease.
AB  - The goal of this article is to review the role of structural neuroimaging in the
      diagnosis of Alzheimer's disease (AD). We present relevant neuroanatomy,
      highlight progress in the domain of AD imaging, and review the clinical
      characteristics of the prodromal phase of AD. We describe the history of the
      diagnostic issue by examining at cross-section and longitudinally the differences
      between patients who have AD and normal controls. We also present how subsequent
      works applied these characteristic traits to the early detection of the prodromal
      disease and to prediction of future decline. The article delineates the
      differences between subjects who have mild cognitive impairment and AD, which
      illustrate the spreading of the pathology with disease progression. The last
      section describes problems encountered in the differential diagnosis.

PMID- 16443493
TI  - Molecular imaging in Alzheimer's disease.
AB  - Molecular imaging represents a new term for a long-standing quest to image
      cellular and molecular processes in vivo. The development of a successful
      molecular imaging approach starts with a well-defined diagnostic question best
      answered using in vivo imaging. A selective target for a particular disease state
      is then identified and a biocompatible probe selective for that target is
      developed. Many of the challenges of finding selective disease targets and probes
      that bind selectively to those targets in vivo are evident in the 25-year history
      of molecular imaging in Alzheimer's disease. This article provides a brief
      overview of molecular imaging in Alzheimer's disease and its potential for early
      diagnosis and treatment development.

PMID- 16443494
TI  - Positron emission tomography diagnosis of Alzheimer's disease.
AB  - Positron emission tomography (PET) imaging of [18F]-2-fluoro-2-deoxy-D-glucose
      (FDG) is accurate in the early detection of Alzheimer's disease (AD) and in the
      differentiation of AD from the other causes of dementia. FDG-PET imaging is
      available widely and performed easily. Different patterns of abnormality with the
      various causes of dementia are well described. Semiquantitative methods of image
      interpretation are available. Medicare covers FDG-PET imaging for the narrow
      indication of differentiation of possible AD from frontotemporal dementia.

PMID- 16443495
TI  - A review of 1H MR spectroscopy findings in Alzheimer's disease.
AB  - Hydrogen-1 MR spectroscopy (MRS) studies demonstrate metabolic differences
      between patients who have Alzheimer's disease (AD) and cognitive normal age
      matched controls. Clinical MRS also shows regional variations in metabolites
      between patients who have AD and those who have other dementias. Single-voxel and
      volumetric standard MRS techniques and automated data processing software are
      available for clinical MR scanners. Improvements in specificity and sensitivity
      of AD diagnosis, using MRS techniques as an adjunct to clinical imaging, are
      under evaluation. Multiparametric data analyses show, however, that metabolite
      changes correlate with in-vitro, postmortem, and metabolic changes and to changes
      in or predictions of cognitive scores.

PMID- 16443496
TI  - Current status of functional MR imaging, perfusion-weighted imaging, and
      diffusion-tensor imaging in Alzheimer's disease diagnosis and research.
AB  - Advanced MR techniques, such as functional MR imaging, perfusion-weighted
      imaging, and diffusion-tensor imaging, offer the capability of detecting early
      functional, hemodynamic, and microstructural alterations in Alzheimer's disease
      before gross anatomic alterations. Most studies of these emerging technologies
      are at the exploratory stage, with the purpose of increasing understanding of the
      underlying disease process and defining cross-sectional differences across
      various subject populations. Assessment of the diagnostic efficacy of these
      technologies in detecting early Alzheimer's disease in its preclinical and
      prodromal stages is ongoing.

PMID- 16443497
TI  - The Alzheimer's disease neuroimaging initiative.
AB  - With increasing life expectancy in developed countries, the incidence of
      Alzheimer's disease (AD) and its socioeconomic impact are growing. Increasing
      knowledge of the mechanisms of AD facilitates the development of treatment
      strategies aimed at slowing down or preventing neuronal death. AD treatment
      trials using clinical outcome measures require long observation times and large
      patient samples. There is increasing evidence that neuroimaging and cerebrospinal
      fluid and blood biomarkers may provide information that may reduce sample sizes
      and observation periods. The Alzheimer's Disease Neuroimaging Initiative will
      help identify clinical, neuroimaging, and biomarker outcome measures that provide
      the highest power for measurement of longitudinal changes and for prediction of
      transitions.

PMID- 16443498
TI  - Physiological and pathological relevance of human uterine LH/hCG receptors.

PMID- 16443499
TI  - Agonistic antibodies directed at the angiotensin II, AT1 receptor in
      preeclampsia.
AB  - Immune mechanisms and circulating mediators may be important in the pathogenesis
      of preeclampsia. We review our findings on agonistic antibodies against the
      angiotensin II (Ang II) receptor (AT1-AA) and their possible role in the
      pathogenesis of this disorder. AT1-AA appear in the course of preeclampsia and
      are largely gone by 6 weeks after delivery. AT1-AA detection relies on a bioassay
      using spontaneously beating neonatal rat cardiomyocytes. Their specificity has
      been documented by other methods, including Western blotting, co-localization,
      and co-immunoprecipitation experiments. AT1-AA induce signaling in vascular cells
      and trophoblasts including transcription factor activation. The signaling results
      in tissue factor production and reactive oxygen species generation, both of which
      have been implicated in preeclampsia. The role of AT1-AA in preeclampsia and
      other severe hypertensive conditions has not yet been proved with certainty.
      However, we believe the findings are compelling and warrant further study.

PMID- 16443500
TI  - Chronic endotoxin exposure causes brain injury in the ovine fetus in the absence
      of hypoxemia.
AB  - OBJECTIVE: Intrauterine infection has been linked to brain injury in human
      infants, although the mechanisms are not fully understood. We recently showed
      that repeated acute exposure of preterm fetal sheep to bacterial endotoxin
      (lipopolysaccharide [LPS]) results in fetal hypoxemia, hypotension, increased
      systemic proinflammatory cytokines, and brain damage, including white matter
      injury. However, it is not clear whether this injury is caused by reduced
      cerebral oxygen delivery or inflammatory pathways independent of hypoxia. The aim
      of the present study was to determine the effects on the fetal brain and placenta
      of a chronic intrauterine inflammatory state, induced by LPS infusion into the
      fetal circulation, a model that did not cause hypoxia. METHODS: At 0.65 of term,
      eight catheterized fetal sheep received intravenous infusions of LPS (5 to 15
      mug) over 5 days; control fetuses received saline. Fetal physiologic responses
      were monitored throughout the infusion. Fetal brain and placental tissues were
      examined histologically 6 days after the conclusion of the infusion. RESULTS: LPS
      infusions did not result in physiologically significant alterations to fetal
      blood gases or mean arterial pressure; however, plasma proinflammatory cytokine
      levels were elevated. Following LPS exposure there was no difference in fetal
      body or brain weights (P >.05); placental weight was reduced (P <.05), consistent
      with reduced placentome cross-sectional area (P <.05). In the cerebral
      hemispheres subcortical white matter injury was present in six LPS-exposed
      fetuses and included axonal damage, microgliosis, oligodendrocyte injury, and
      increased beta amyloid precursor protein (beta-APP) expression. CONCLUSIONS:
      Chronic, systemic exposure of the fetus to LPS resulted in fetal brain damage in
      the absence of hypoxemia or hypotension, although the resulting injury was less
      severe than following repeated acute exposure.

PMID- 16443501
TI  - Leukocyte density and proinflammatory mediator expression in regional human fetal
      membranes and decidua before and during labor at term.
AB  - OBJECTIVES: The region of fetal membranes overlying the cervix, known as the zone
      of altered morphology (ZAM), is considered to be the principle site of membrane
      inflammatory activity and extracellular matrix remodelling. We wished to quantify
      the relative contribution of each area of fetal membranes to the inflammatory
      process of parturition. Specifically, we aimed to quantify and compare (1)
      leukocyte densities in three regions of fetal membranes and decidua before and
      during spontaneous labor at term, and (2) mRNA expression of interleukin (IL)
      1beta, IL-6, IL-8, cyclo-oxygenase type 1 (COX-1), and COX-2 in three regions of
      fetal membranes and decidua before and during spontaneous labor at term. METHODS:
      Biopsies of fetal membranes and decidua were obtained from pregnant women
      delivered by cesarean section at term both before and during spontaneous labor (n
      = 8 both groups). Fetal membranes were sampled from three areas, the ZAM, midzone
      (MZ), and periplacental (PP) regions. Leukocytes were identified by
      immunohistochemistry and their density quantified. Inflammatory mediator
      expression was quantified using TaqMan technology (Applied Biosystems, Foster
      City, CA). RESULTS: There was a significantly greater density of leukocytes in
      (1) the PP region of membranes compared with the ZAM, and (2) the decidua
      compared with amnion, amniotic connective tissue, and chorion. IL-1beta, IL-6,
      and IL-8 mRNA expression was significantly greater in all regions following
      spontaneous labor compared with nonlaboring tissues. There were no regional
      differences in cytokine expression within the fetal membranes. Choriodecidua
      expressed significantly more IL-1beta mRNA than amnion. Amnion expressed more COX
      2 mRNA than choriodecidua. CONCLUSIONS: All regions of fetal membranes and
      decidua contribute to the inflammatory process of human parturition; however,
      their relative contributions differ in magnitude. Although the ZAM may be
      specifically important for membrane rupture, it does not appear to play a key or
      exclusive role in the other inflammatory processes of parturition. When studying
      fetal membranes, it is relevant to identify and define the area sampled for
      consistency and comparison with other studies.

PMID- 16443503
TI  - Effect of chronic maternal methadone therapy on intrapartum fetal heart rate
      patterns.
AB  - OBJECTIVE: Treatment of maternal opioid dependence with methadone is associated
      with a delay in fetal heart rate (FHR) accelerations in nonstress tests. The
      objective of this investigation was to determine the effect of methadone
      maintenance therapy on intrapartum FHR patterns. METHODS: This retrospective
      cohort study compared intrapartum FHR tracings from 56 methadone-treated patients
      > or =36 weeks gestation with a control group of nonsubstance using patients
      matched for maternal age, parity, gestational age, and ethnicity. Blinded FHR
      interpretation included the recording of baseline, variability, accelerations,
      and late or severe variable decelerations. The 8-point FHR scoring system was
      based on the National Institute of Child Health and Human Development Research
      Planning Workshop guidelines. We considered a 25% reduction in the score during
      the latent phase to be significant. RESULTS: The median maintenance dose of
      methadone was 70 mg daily, with a range between 20 mg and 130 mg. Each patient
      tested negative for other substances on urine screening before admission. The
      significantly lower FHR score in the methadone group (mean difference, 1.4; 95%
      confidence interval, 1.1 to 1.7) was attributed to a lower baseline (P <.05),
      less moderate or marked variability (P <.01), and a lower proportion of
      accelerations during the first stage of labor (P <.01). A higher proportion of
      methadone-exposed fetuses had late or severe variable decelerations in the second
      stage (44.2% vs 22.9%; P <.03). Analgesic needs, operative vaginal or cesarean
      delivery rates, and Apgar scores less than 7 at 1 and 5 minutes were not
      significantly different between the two groups. CONCLUSIONS: Chronic maternal
      methadone treatment affects intrapartum FHR patterns by reducing the variability,
      baseline, and proportion of accelerations during the first stage. These subtle
      drug-induced effects do not compromise intrapartum decision-making or immediate
      newborn adjustments.

PMID- 16443502
TI  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha gene
      variations are not associated with gestational diabetes mellitus.
AB  - OBJECTIVE: Epidemiologic, pathophysiologic, and genetic data suggest a close link
      between gestational diabetes mellitus (GDM) and type 2 diabetes. Previous studies
      yielded controversial results on the impact of peroxisome proliferator-activated
      receptor gamma coactivator-1alpha (PGC-1) gene variations on the development of
      type 2 diabetes mellitus. Therefore, we examined two common single nucleotide
      polymorphisms (SNP) of this gene in women with GDM. METHODS: We assessed a total
      of 875 women by oral glucose tolerance testing (OGTT). Two hundred women of this
      population, 100 patients with an abnormal OGTT and 100 normal controls, were
      randomly selected. DNA samples isolated from the blood of the control and study
      groups were analyzed with respect to the SNP Gly482Ser and Thr394Thr of the PGC-1
      gene using polymerase chain reaction (PCR) amplification and restriction
      analysis. Furthermore, a potential interaction between the Gly482Ser and the
      Thr394Thr variant on the risk of GDM was investigated. RESULTS: Women with GDM
      were significantly older (32.2 +/-5.5 years vs 29.7 +/- 6.1 years; P = .005), had
      higher body mass indices (BMI; 28.0 +/- 7.1 kg/m2 vs 25.0 +/- 5.7 kg/m2; P =
      .002) and displayed higher hemoglobin A1c (HbA1c) values (5.6 +/- 0.9 vs 4.9 +/-
      0.5; P <.001). There was no significant difference between the allele
      distribution of the two polymorphisms in women with and without GDM. No
      significant associations between the two polymorphisms and BMI or OGTT values
      were observed. When the different haplotype combinations of the two loci were
      analyzed for the risk of GDM, no significant association could be found.
      CONCLUSION: Based on our data, the Gly482Ser and the Thr394Thr polymorphisms of
      the PGC-1 gene are not associated with the development of GDM.

PMID- 16443504
TI  - Pharmacokinetics of a controlled-release misoprostol vaginal insert at term.
AB  - OBJECTIVE: The objective of this investigation was to report the pharmacokinetic
      properties of misoprostol administered intravaginally to women at term via a
      controlled-release hydrogel polymer insert. METHODS: This open-label, dose
      escalation trial consisted of 31 nulliparous women at term who were treated
      intravaginally in cohorts of six with inserts containing reservoirs from 25
      through 300 microg (7 at 200 microg) of misoprostol. Inserts remained
      intravaginally until the patient went into labor, developed adverse events, or
      completed 24 hours of treatment. Complete data about residual drug in the inserts
      and plasma concentrations of misoprostol acid were gathered for 27 and 25
      patients, respectively. RESULTS: Misoprostol was released at a constant rate
      (5.1% total dose per hour) with the amount absorbed being directly proportional
      to the dose reservoir. For the 25-, 50-, 100-, 200-, and 300-microg reservoir
      doses, the maximum median plasma concentrations were 6.4, 11.3, 21.7, 40.8, and
      74.2 pg/mL, respectively, and the area under the curve until drug removal was 39,
      117, 223, 269, and 477 pg x h/mL. Regardless of dose, the peak plasma
      concentration occurred at approximately 7 hours after insertion and the
      elimination half-life of the misoprostol acid was 0.55 hours (95% confidence
      interval, 0.36 to 1.32 hours). CONCLUSIONS: Misoprostol is released from the
      vaginal insert in a controlled manner and is eliminated rapidly after removal.
      Pharmacokinetic parameters are proportional to the reservoir dose.

PMID- 16443505
TI  - Markers of oxidative stress in placental villi exposed to ethanol.
AB  - OBJECTIVE: Ethanol exposure during pregnancy may result in fetal alcohol syndrome
      (FAS). The mechanism by which this occurs is unknown. Recent studies in several
      organ systems, including the placenta, suggest that oxidative stress is involved.
      In this study we investigated the presence and levels of three oxidative stress
      markers in placental villous tissue exposed to ethanol. METHODS: Villous tissues
      from normal placentas were perfused with Dulbeco's modified Eagle's medium (DMEM)
      with HEPES buffer, sodium bicarbonate, and glucose at pH 7.4. After
      stabilization, 100 mM ethanol was added to the perfusate. After 2 hours of
      perfusion, the tissue was removed, fixed and stained for nitrotyrosine, 4-hydroxy
      2-nonenal (4HNE) and 8-hydroxyguanosine (8-OHDG). Staining within the
      trophoblasts was quantified with densitometry. RESULTS: Nitrotyrosine and 4HNE
      immunostaining was seen in the trophoblasts. 4HNE was also seen in the stroma. In
      contrast, 8-OHDG was seen only in the stroma and endothelial cells in the fetal
      circulation. Ethanol exposure significantly increased nitrotyrosine levels in the
      trophoblasts beyond levels in the control tissue. Nitrotyrosine and 8-OHDG levels
      were also increased in stroma. CONCLUSION: Within the placental villi, markers of
      oxidative stress are present in the trophoblasts and stroma after a short period
      of ethanol exposure. There is an increase in oxidative stress, primarily
      involving the nitric oxide pathway, in the trophoblasts as well as DNA damage in
      the stroma. Lipid peroxidation is not acutely changed in our 2-hour exposure
      window.

PMID- 16443506
TI  - Ovarian dysfunction in peripubertal hyperinsulinemia.
AB  - OBJECTIVE: Increasing evidence suggests that hyperinsulinemia plays an important
      role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the timing
      for the onset of hyperinsulinemia is not clear. The objective of this study was
      to examine the effect of peripubertal hyperinsulinemia on the maturing female
      reproductive axis. METHODS: Hyperinsulinemia was induced in 28-day-old
      peripubertal female rats by infusing insulin (0.04 IU/d) via subcutaneously
      implanted Alzet minipumps (Model #2004; Durect Corp, Cupertino, CA; constant flow
      rate 0.25 muL/h) for 4 weeks. Control animals were administered normal saline.
      Estrus cyclicity was monitored regularly. Upon termination of the experimental
      period, the animals were killed, trunk blood and pituitaries were collected for
      hormone assays, and ovaries were collected for histological and
      immunocytochemical studies. RESULTS: In contrast to the control animals,
      hyperinsulinemic animals had (1) erratic estrus cycles, with prolonged (2 to 3
      days) metestrus-diestrus or diestrus-proestrus stages; (2) significantly (P <.05)
      decreased levels of serum progesterone, and significantly (P <.05) increased
      levels of serum testosterone and dehydroepiandrostene sulfate; (3) prematurely
      luteinized ovarian follicles with prominent thecal and interfollicular stromal
      proliferation; and (4) markedly reduced expression of growth differentiation
      factor-9 (GDF-9) and activin receptors (ActR) I and IB in the ovaries.
      CONCLUSION: Peripubertal hyperinsulinemia in rats causes hormonal and ovarian
      changes similar to those in women with PCOS. Based on these novel findings, we
      speculate that peripubertal hyperinsulinemia may be a risk factor for the
      development of PCOS later in life.

PMID- 16443507
TI  - Luteinizing hormone in premenopausal women may stimulate uterine leiomyomata
      development.
AB  - OBJECTIVE: Human chorionic gonadotropin (hCG) has proliferative effects on
      uterine smooth muscle and leiomyoma tissue in vitro. We hypothesized that
      luteinizing hormone (LH) would have the same effect by activating the LH/hCG
      receptor, and it would follow that premenopausal women with higher basal LH
      levels would be more likely to have leiomyomata. METHODS: Randomly selected
      women, aged 35 to 49 years, from a prepaid health plan were screened for
      leiomyomata with pelvic ultrasound. Urine samples collected during the first or
      last 5 days of the menstrual cycle were analyzed for LH by immunofluorometric
      assay, and concentrations were corrected for creatinine (n = 523). Logistic
      regression and Bayes analyses were used to evaluate the association of LH with
      presence and size of leiomyomata, adjusting for age, and other risk factors.
      RESULTS: Women with higher LH were more likely to have leiomyomata (adjusted odds
      ratios for second and third tertiles were 1.7 and 2.0 compared with lower
      tertile; 95% confidence intervals, 1.0 to 2.7 and 1.2 to 3.4, respectively). The
      association was stronger for large leiomyomata. Bayes analyses designed to
      estimate LH effects on tumor onset separately from tumor growth showed
      significantly accelerated tumor onset but little evidence of effects on tumor
      growth. Age, an independent risk factor for leiomyomata, was not affected by
      inclusion of LH in the logistic models. CONCLUSIONS: As hypothesized, women with
      higher LH were more likely to have leiomyomata, but this did not explain the age
      related increase in leiomyomata during perimenopausal ages. Determining whether
      LH is causal or a marker for susceptibility will require further research.

PMID- 16443508
TI  - Catechol-O-methyltransferase polymorphism is associated with increased uterine
      leiomyoma risk in different ethnic groups.
AB  - OBJECTIVES: Uterine leiomyomas (ULMs) are estrogen-dependent tumors that are more
      common in African American women. The etiology for such ethnic disparity is
      currently unknown. Catechol-O-methyltransferase (COMT) is an essential enzyme in
      estrogen metabolism. In the current study, we investigated the association of the
      functional COMT Val158Met polymorphism with ULM in different ethnic groups. We
      also studied the biologic role of COMT in tumor formation in human and rat
      leiomyoma cell lines and the potential therapeutic utility of COMT inhibitors.
      METHODS: The genotype frequencies of the functional COMT Val158Met polymorphism
      among participants with (186 women) or without (142 women) ULMs were compared, as
      was the differential ethnic distribution of that polymorphism using polymerase
      chain reaction (PCR) and restriction-fragment linkage polymorphism.
      Proliferation, Western blot, and reporter transactivation analyses were applied
      to myometrial and leiomyoma cells representative of different COMT genotypes.
      RESULTS: Women with the high-activity COMT Val/Val genotype are 2.5 times more
      likely to develop ULMs than women with other genotypes (confidence interval,
      1.017 to 6.151; P <.001). The prevalence of this genotype was significantly
      higher in African American women (47%) compared with white (19%) or Hispanic
      (30%) women (P = .003). Myometrial cell lines expressing the Val/Val genotype
      exhibited significantly enhanced responses to estrogen in proliferation and in
      estrogen-responsive element reporter assays. COMT-specific inhibitors reversed
      such a response and induced apoptosis. Myometrial specimens from Val/Val women
      demonstrated distinct estrogen-regulated gene expression that was consistent with
      enhanced proliferation and decreased apoptosis. CONCLUSIONS: The high-activity
      COMT Val/Val genotype is associated with increased risk of ULM. Our results
      provide a possible explanation for the higher prevalence of ULMs among African
      American women and offer a potential new target for nonsurgical treatment using
      COMT inhibitors.

PMID- 16443509
TI  - Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) induces apoptosis
      in ovarian cancer cells.
AB  - OBJECTIVES: Triapine (Vion Pharmaceuticals, New Haven, CT) is a potent
      ribonucleotide reductase inhibitor which exerts its antineoplastic activity by
      inhibiting DNA synthesis and repair. The objectives of this study were: (1) to
      determine whether Triapine has cytotoxic effects on epithelial ovarian cancer
      (EOC) cells; (2) to characterize the apoptotic cascade induced in response to
      this agent; and (3) to determine its utility in combination treatment with
      carboplatin and paclitaxel. METHODS: Five EOC cell lines were treated with
      tenfold dilutions of Triapine (0.1 to 100 microM) for 24 and 48 hours. Cell
      viability was determined by the CellTiter 96 AQueous One Solution Cell
      Proliferation Assay (Promega Corp, Madison, WI) and the morphologic features of
      apoptosis were observed using Hoechst staining. The apoptotic cascade was
      characterized by Western blot analyses. RESULTS: All EOC cell lines treated with
      Triapine showed decreased cell viability in a time- and dose-dependent manner.
      Hoechst staining revealed nuclear shrinkage and chromatin condensation and
      fragmentation, which correlated with the occurrence of apoptosis. Western blots
      demonstrated that Bid activation was one of the initiating signals involved in
      the cascade. In addition, cleavage of XIAP and down-regulation of Akt were
      observed. We also demonstrated that Triapine enhances the cytotoxic effects of
      carboplatin and paclitaxel. CONCLUSIONS: The present findings demonstrate that
      Triapine induces cell death through the induction of apoptosis. The initial
      activation of Bid indicates the involvement of the mitochondrial pathway. The
      demonstration that Triapine is an effective addition to a carboplatin regimen
      suggests the possibility of a new combination therapy for ovarian cancer.

PMID- 16443510
TI  - Dendritic cell immunotherapy for the treatment of neoplastic disease.
AB  - It has long been promised that dendritic cell immunotherapy would revolutionize
      the treatment of neoplastic disease. Now, more than 10 years since the
      publication of the first clinical data, a firmer understanding of immunology and
      dendritic cell biology is beginning to produce interesting clinical results. This
      article reviews the clinical trials that established many of the concepts with
      which today's investigators are achieving improved results, discusses issues in
      dendritic cell immunotherapy that are currently unresolved, and offers a
      perspective on the strategies that the authors believe will be important for the
      design of future vaccine trials, including the use of Toll-like receptor agonists
      as maturation agents, the accessory use of the plasmacytoid dendritic cell
      subset, and the maximization of T-cell help.

PMID- 16443511
TI  - Toward biomarkers for chronic graft-versus-host disease: National Institutes of
      Health consensus development project on criteria for clinical trials in chronic
      graft-versus-host disease: III. Biomarker Working Group Report.
AB  - Biology-based markers that can be used to confirm the diagnosis of chronic graft
      versus-host disease (GVHD) or monitor progression of the disease could help in
      the evaluation of new therapies. Biomarkers have been defined as any
      characteristic that is objectively measured and evaluated as an indicator of a
      normal biologic or pathogenic process, a pharmacologic response to a therapeutic
      intervention, or a surrogate end point intended to substitute for a clinical end
      point. The following applications of biomarkers could be useful in chronic GVHD
      clinical trials or management: (1) predicting response to therapy; (2) measuring
      disease activity and distinguishing irreversible damage from continued disease
      activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing
      chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the
      balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or
      GVT); and (7) serving as a surrogate end point for therapeutic response. Such
      biomarkers can be identified by either hypothesis-driven testing or by high
      throughput discovery-based methods. To date, no validated biomarkers have been
      established for chronic GVHD, although several candidate biomarkers have been
      identified from limited hypothesis-driven studies. Both approaches have merit and
      should be pursued. The consistent treatment and standardized documentation needed
      to support biomarker studies are most likely to be satisfied in prospective
      clinical trials.

PMID- 16443512
TI  - Recommended screening and preventive practices for long-term survivors after
      hematopoietic cell transplantation: joint recommendations of the European Group
      for Blood and Marrow Transplantation, the Center for International Blood and
      Marrow Transplant Research, and the American Society of Blood and Marrow
      Transplantation.
AB  - More than 40000 hematopoietic cell transplants (HCTs) are performed worldwide
      each year. With improvements in transplant technology, larger numbers of
      transplant recipients survive free of the disease for which they were
      transplanted. However, there are late complications that can cause substantial
      morbidity. Many survivors are no longer under the care of transplant centers, and
      many community health care providers may be unfamiliar with health matters
      relevant to HCT. The Center for International Blood and Marrow Transplant
      Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT),
      and American Society for Bone Marrow Transplantation (ASBMT) have developed these
      recommendations to offer care providers suggested screening and prevention
      practices for autologous and allogeneic HCT survivors.

PMID- 16443513
TI  - Skin explant model of human graft-versus-host disease: prediction of clinical
      outcome and correlation with biological risk factors.
AB  - A human skin explant model has been used to predict the clinical outcome and to
      study the immunopathology of human graft-versus-host disease (GVHD). Whether the
      model gives the same predictive effect for GVHD in different hematopoietic stem
      cell transplantation (HSCT) settings has not been assessed. It is also unknown
      whether the skin explant result reflects the known biological risk factors for
      clinical GVHD. In this study, the skin explant model was used to detect graft
      versus-host reactions (GVHR) in vitro for 225 eligible patient/donor pairs. The
      predicted skin GVHR grade was correlated with the outcome of clinical GVHD, as
      well as HLA matching status, sex mismatches, and patient age. In sibling HSCT
      under either myeloablative or reduced-intensity conditioning, a significant
      correlation was observed between the predicted skin GVHR and clinical GVHD (P <
      .001 and P = .033, respectively). In HSCT using unrelated donors, the involvement
      of T-cell depletion led to a sharp increase in false-positive GVHR results, and
      no correlation was observed between the predicted skin GVHR and clinical GVHD.
      The skin GVHR grade correlated significantly with the HLA matching status (HLA
      matched sibling pairs, HLA-matched unrelated pairs, and HLA-unmatched unrelated
      pairs). Furthermore, HLA-matched sibling pairs with a female-to-male sex mismatch
      had a significantly higher overall skin GVHR grade and a higher ratio of high-
      versus low-grade skin GVHR than the sibling pairs with all other sex
      combinations. Patient age was not reflected in the skin explant result. In
      conclusion, the predictive value of the skin explant model for aGVHD varies
      depending on the clinical transplant protocols, such as the type of GVHD
      prophylaxis used. Nevertheless, the skin explant model remains a unique in vitro
      system that provides an in situ histopathologic readout for studying
      alloreactivity and human GVHD. The model has also the potential to aid the
      development of novel prophylaxis and treatment for GVHD.

PMID- 16443514
TI  - Impaired allogeneic activation and T-helper 1 differentiation of human cord blood
      naive CD4 T cells.
AB  - CD4 T cells, particularly those of the T-helper 1 (Th1) subset, are important
      effectors in alloimmune diseases, such as graft-versus-host disease, and in
      controlling infections with intracellular pathogens. Thus, it is plausible that
      impaired neonatal CD4 T-cell immunity might contribute to the low incidence of
      acute graft-versus-host disease after allogeneic transplantation of hematopoietic
      stem cells using cord blood (CB) compared with adult sources of hematopoietic
      stem cells. In support of this hypothesis, we found that CB naive CD4 T cells had
      reduced activation and impaired early Th1 differentiation compared with adult
      peripheral blood naive CD4 T cells after stimulation by allogeneic dendritic
      cells derived from adult monocytes. Early Th1 polarization was dependent on
      interleukin-12 and CD154, and CB CD4 T cell/dendritic cell co-cultures had
      impaired expression of both proteins. CB naive CD4 T cells had low basal levels
      of signal transduction and activation of transcription 4 messenger RNA and
      protein, and, after alloantigen stimulation, reduced interleukin-12-induced
      signal transduction and activation of transcription 4 tyrosine phosphorylation,
      compared with adult peripheral blood naive T cells. Lastly, FoxP3 protein
      expression, a marker for regulatory CD25(high) CD4 T cells, was lower for naive
      CD4 T cells of CB compared with those of adult peripheral blood, which argued
      against increased T-regulatory activity as a mechanism for the decreased Th1
      differentiation of CB CD4 T cells. Together, these intrinsic limitations in T
      cell activation and Th1 differentiation may impair the ability of T cells in CB
      and the neonate to respond to allogeneic or infectious challenges.

PMID- 16443515
TI  - Nonmyeloablative stem cell transplantation is an effective therapy for refractory
      or relapsed hodgkin lymphoma: results of a spanish prospective cooperative
      protocol.
AB  - We report the results of reduced-intensity conditioning allogeneic stem cell
      transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty
      patients with relapsed or refractory HL were homogeneously treated with an RIC
      protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2)
      intravenously) and cyclosporin A and methotrexate as graft-versus-host disease
      (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of
      chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%)
      had experienced treatment failure with a previous autologous stem cell
      transplantation. Twenty patients (50%) were allografted in resistant relapse, and
      38 patients received hematopoietic cells from an HLA-identical sibling. Five
      patients (12%) died from early transplant-related mortality (before day +100
      after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD
      developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31
      evaluable patients. The response rate 3 months after the allo-RIC was 67% (21
      [52%] complete remissions and 6 [15%] partial remissions). Eleven patients
      received donor lymphocyte infusions (DLIs) for disease relapse. The response rate
      after DLI was 54% (3 complete remissions and 3 partial remissions). Overall
      survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/-
      10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse
      prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS
      (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior
      autologous hematopoietic stem cell transplantation, results were especially good
      for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75%
      +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is
      feasible in heavily pretreated HL patients and has an acceptable early transplant
      related mortality. Results are better in patients allografted in sensitive
      disease. Both responses observed after the development of GVHD and DLI may
      suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective
      therapeutic approach for patients who have had treatment failure with a previous
      autologous hematopoietic stem cell transplantation.

PMID- 16443516
TI  - Results of the cord blood transplantation study (COBLT): outcomes of unrelated
      donor umbilical cord blood transplantation in pediatric patients with lysosomal
      and peroxisomal storage diseases.
AB  - The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart,
      Lung, and Blood Institute, is a phase II multicenter study designed to evaluate
      the use of cord blood in allogeneic transplantation. In this report, we evaluated
      the outcomes of cord blood transplantation in 69 patients with lysosomal and
      peroxisomal storage diseases. Patients with mucopolysaccharidoses I to III,
      mucolipidoses (ML) II (n = 36), adrenoleukodystrophy (n = 8), metachromatic
      leukodystrophy (n = 6), Krabbe disease (n = 16), and Tay-Sachs disease (n = 3)
      were enrolled between August 1999 and June 2004. All patients received the same
      preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive
      care. End points included survival, engraftment, GVHD, and toxicity. Sixty-nine
      patients (64% men; 81% white) with a median age of 1.8 years underwent
      transplantation with a median cell dose of 8.7 x 10(7)/kg. One-year survival was
      72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil
      engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of
      25 days. Grade II to IV acute GVHD occurred in 36% of patients. Cord blood donors
      are readily available for rapid transplantation. Cord blood transplantation
      should be considered as frontline therapy for young patients with lysosomal and
      peroxisomal storage diseases.

PMID- 16443517
TI  - Consolidation with high-dose combination alkylating agents with bone marrow
      transplantation significantly improves disease-free survival in hormone
      insensitive metastatic breast cancer in complete remission compared with
      intensive standard-dose chemotherapy alone.
AB  - We conducted this study to determine event-free and overall survival among women
      with hormone-insensitive or hormone-resistant metastatic breast cancer receiving
      consolidation with high-dose chemotherapy (HDC) and hematopoietic support versus
      no further chemotherapy after intensive induction chemotherapy. Eligible patients
      received induction doxorubicin, 5-fluorouracil, and methotrexate (AFM) for 2 to 4
      cycles. Women in complete remission were randomized to immediate HDC with
      cyclophosphamide, cisplatin, and carmustine followed by autologous hematopoietic
      support or to no further therapy. Patients on the observation arm of therapy were
      offered salvage HDC at the time of relapse. Partial responders to AFM were
      offered immediate HDC. A total of 425 patients were enrolled onto the study. The
      median event-free survival for women randomized to induction therapy alone was
      3.8 months, compared with 9.7 months for women who completed HDC (P < .006). Of
      the patients randomized to observation, 5 (10%) of 51 remain event free, compared
      with 13 (26%) of 49 patients who underwent immediate HDC (P = .03). Of women
      converted to a complete response by salvage HDC after a partial response to AFM,
      overall survival was similar to that in women randomized to immediate HDC. Follow
      up is now in excess of 5 years. The 5-year event-free survival is 15% (95%
      confidence interval, 12%-18%), and the 5-year overall survival is 20% (95%
      confidence interval, 17%-25%). Immediate HDC after a complete response to AFM
      produced some durable long-term responses in hormone-insensitive/-resistant
      metastatic breast cancer. Salvage HDC converted 30% of partial responders to
      complete responders with similar survivals. The addition of novel targeted
      therapies to intensive-dose chemotherapy regimens may further improve survival in
      metastatic breast cancer.

PMID- 16443518
TI  - Pretransplantation consolidation chemotherapy decreases leukemia relapse after
      autologous blood and bone marrow transplants for acute myelogenous leukemia in
      first remission.
AB  - Controversy exists over whether pretransplantation consolidation chemotherapy
      affects the outcome of subsequent autotransplantation for acute myelogenous
      leukemia (AML). The current study was undertaken to determine the association
      between previous consolidation and outcome of autotransplantation for AML in
      first remission. Posttransplantation outcomes of 146 patients receiving no
      consolidation were compared with those of 244 patients receiving standard-dose
      (<1 gm/m(2)) and 249 patients receiving high-dose (1-3 gm/m(2)) cytarabine, using
      proportional hazards regression to adjust for differences in prognostic
      variables. One-year transplantation-related mortality was similar among the
      cohorts. Five-year relapse rates were 49% (95% confidence interval CI} = 39%-58%)
      with no consolidation, 35% (95% CI = 29%-42%) with standard-dose cytarabine, and
      40% (95% CI = 33%-48%) with high-dose cytarabine (P = .07). Five-year leukemia
      free survival rates were 39% (95% CI = 30%-47%) with no consolidation, 53% (95%
      CI = 46%-60%) with standard-dose cytarabine, and 48% (95% CI = 40%-56%) with high
      dose cytarabine (P = .03). Similarly, 5-year overall survival was better in those
      patients receiving consolidation: 42% (95% CI = 34%-51%) with no consolidation,
      59% (95% CI = 52%-65%) with standard-dose cytarabine, and 54% (95% CI = 46%-61%)
      with high-dose cytarabine (P = .01). Although most patients received 1 or 2
      cycles of consolidation, the number of courses had no detectable effect on
      transplantation outcome. In multivariate analysis, risks of relapse and treatment
      failure were lower in the patients receiving consolidation, especially among
      those patients receiving blood cell grafts. Outcomes with standard-dose and high
      dose cytarabine were similar. Based on our findings, we recommend that patients
      with AML in first remission receive consolidation before undergoing
      autotransplantation.

PMID- 16443519
TI  - Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor
      allogeneic stem-cell transplantations conditioned with fludarabine and low-dose
      total body irradiation.
AB  - We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease
      (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from
      a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with
      advanced hematologic malignancies, who were poor candidates for a conventional
      myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day 
      2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral
      blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day
      3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered
      from day +100 to day +180 in those patients with indolent malignancies (n = 25),
      and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen
      toxicities and myelosuppression were mild, allowing 75% of patients to have
      entirely outpatient transplantations. One patient (3%) experienced a nonfatal
      graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%,
      respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84).
      Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a
      median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or
      elicited after tumor progression (n = 5). Five patients experienced
      transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related
      multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median
      follow-up of 19 months (range, 2-41 months), the overall survival, progression
      free survival, and disease-free survival rates are 62.5%, 50%, and 40%,
      respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is
      associated with encouraging rates of GVHD control.

PMID- 16443520
TI  - Gastrointestinal graft-versus-host disease in recipients of autologous
      hematopoietic stem cells: incidence, risk factors, and outcome.
AB  - Graft-versus-host disease (GVHD) is seen in skin, intestinal mucosa, and liver
      after autologous stem cell transplantation. We reviewed 681 consecutive patients
      to estimate the probability of gastrointestinal (GI) GVHD, response to treatment,
      risk factors for development, and effect on survival. GI GVHD was defined by
      persistent symptoms, mucosal abnormalities at endoscopy, and histology showing
      apoptotic crypt cells with or without lymphoid infiltrates. The proportion of
      patients with GI GVHD was 90/681 (13%). Nausea and vomiting occurred in 90% and
      diarrhea in 40%. The mean time to developing symptoms was day +15, that to
      histologically proven diagnosis was day +42, and that to starting prednisone
      treatment was day +45 after stem cell infusion. Treatment with a short course of
      prednisone effected durable responses in 79% of patients, and an additional 18%
      responded to a second course of prednisone. A multivariable logistic regression
      model demonstrated that the combined factor of a diagnosis of breast cancer or
      hematologic malignancy and female sex was statistically significantly associated
      with the probability of GI GVHD (P = .003). Survival in patients with GI GVHD was
      not statistically different than that in those without GVHD. We conclude that
      women with breast cancer or hematologic malignancy are more likely to develop GI
      GVHD after autologous transplantation, and that treatment with prednisone was
      effective.

PMID- 16443521
TI  - High-dose weekly AmBisome antifungal prophylaxis in pediatric patients undergoing
      hematopoietic stem cell transplantation: a pharmacokinetic study.
AB  - Disseminated fungal infection causes significant morbidity and mortality in
      children undergoing hematopoietic stem cell transplantation (HSCT). The
      widespread use of prophylactic oral triazoles has limitations of poor absorption,
      interindividual variability in metabolism, and hepatic toxicity. AmBisome
      (amphotericin B liposomal complex) has a better safety profile than the parent
      drug amphotericin B and produces higher plasma and tissue concentrations. We
      hypothesized that once-weekly high-dose AmBisome therapy could provide adequate
      fungal prophylaxis for immunocompromised children undergoing HSCT. We performed a
      pharmacokinetic pilot study to determine whether once-weekly high-dose AmBisome
      administration would result in effective concentrations throughout the dosing
      interval. A total of 14 children (median age, 3 years, 1 month; range, 4.5 months
      9 years, 9 months) undergoing HSCT received once-weekly intravenous AmBisome
      prophylaxis (10 mg/kg as a 2-hour infusion). Blood samples for pharmacokinetic
      measurements were drawn around the first and the fourth weekly doses. The
      concentration of non-lipid-complexed amphotericin in plasma was determined by a
      validated bioassay. Pharmacokinetic parameters after single doses and during
      steady state were calculated using standard noncompartmental methods. AmBisome
      was well tolerated at this dose. Complete pharmacokinetic profiles for weeks 1
      and 4 were obtained in 12 patients. The half-life calculated in this pediatric
      population was shorter on average than reported in adults (45 hours vs 152
      hours). The volume of distribution correlated best with body weight (R(2) = .55),
      and clearance was best predicted by initial serum creatinine level (R(2) = .19).
      Mean (+/- standard deviation) individual plasma trough concentrations were 0.23
      (0.13) mg/L after single doses and 0.47 (0.41) mg/L after multiple doses. Mean
      steady-state area under the curve was higher at week 4 than after a single dose
      (P < .05). Single-dose and steady-state pharmacokinetic profiles were similar in
      8 patients, whereas in 4 patients the week 4 profile showed nonlinear
      elimination. However, plasma concentrations at 7 days (Cmin) were not
      significantly different after the first and fourth doses, suggesting no
      significant accumulation over the course of therapy. Our data show measurable
      amphotericin B plasma concentrations 7 days after high-dose infusion of AmBisome.
      This suggests that once-weekly dosing, as described in this study, may provide
      useful protection against fungal infections.

PMID- 16443522
TI  - Dapsone-induced methemoglobinemia after hematopoietic stem cell transplantation.

PMID- 16443524
TI  - Electrocardiographic changes predicting sudden death in propofol-related infusion
      syndrome.
AB  - BACKGROUND: The occurrence of metabolic acidosis, rhabdomyolysis, hyperkalemia,
      and sudden cardiac death after long-term, high-dose propofol infusion has been
      referred to as propofol infusion syndrome (PRIS). OBJECTIVES: The purpose of this
      study was to explore the ECG abnormalities observed in a patient with PRIS in
      order to identify possible pathophysiologic mechanisms of the syndrome. METHODS:
      ECG changes in the index case were characterized by down-sloping ST-segment
      elevation in precordial leads V1 to V3 (Brugada-like ECG pattern). We
      subsequently assessed the relationship between this ECG pattern and the propofol
      infusion rate, the development of arrhythmias, and the occurrence of sudden death
      in a previously described cohort of 67 head-injured patients, seven of whom had
      been identified as having PRIS. RESULTS: Six of the PRIS patients developed the
      ECG pattern of ST-segment elevation in leads V1 to V3 and died within hours of
      irrecoverable electrical storm. This ECG pattern was the first aberration
      recorded hours before the death of these patients. ECGs that were available for
      30 of 60 unaffected patients exhibited a normal pattern. None of the 60 patients
      developed ventricular arrhythmias. CONCLUSION: Our findings indicate that
      development of an acquired Brugada-like ECG pattern in severely head-injured
      patients is a sign of cardiac electrical instability that predicts imminent
      cardiac death. Future studies will determine whether such an ECG pattern also
      predicts imminent cardiac arrhythmia in other patient populations.

PMID- 16443525
TI  - Toward a prediction of sudden death in propofol-related infusion syndrome.

PMID- 16443526
TI  - Long-term evaluation of atrial fibrillation ablation guided by noninducibility.
AB  - BACKGROUND: Pulmonary vein (PV) isolation and linear lesions are effective in
      eliminating paroxysmal atrial fibrillation (AF), but linear lesions probably are
      not required in all patients. Noninducibility of AF has been shown to be
      associated with freedom from arrhythmia in 87% of patients. OBJECTIVES: The
      purpose of this study was to prospectively evaluate the role of noninducibility
      in guiding a stepwise approach tailored to the patient. METHODS: In 74 patients
      (age 53 +/- 8 years) with paroxysmal AF, PV isolation was performed during
      induced or spontaneous AF. If AF was inducible after PV isolation, one to two
      additional linear lesions were placed at the mitral isthmus and/or left atrial
      roof, with the endpoint of noninducibility of AF or atrial flutter. Inducibility
      (AF/atrial flutter, lasting > or = 10 minutes) was assessed using burst pacing at
      an output of 20 mA down to refractoriness from the coronary sinus and both atrial
      appendages. RESULTS: In 42 patients (57%), PV isolation restored sinus rhythm and
      rendered AF noninducible. In the 32 patients with persistent or inducible AF
      after PV isolation, a single linear lesion achieved noninducibility in 20,
      whereas two linear lesions were required in 12 and resulted in conversion to
      sinus rhythm and noninducibility in 10. Using this stepwise approach, a total of
      69 patients (93%) were rendered noninducible. During follow-up of 18 +/- 4
      months, 67 patients (91%) were free from arrhythmia without antiarrhythmic drugs.
      Repeat procedures were performed in 23 patients: repeat ablation was required to
      consolidate prior targets in 15 patients (20%), and "new" linear lesions, which
      were not predicted by inducibility during the index procedure, were required in 8
      (11%). CONCLUSION: Noninducibility can be used as an endpoint for determining the
      subset of patients with paroxysmal AF who require additional linear lesions after
      PV isolation. This tailored approach is effective in 91% of patients while
      preventing delivery of unnecessary linear lesions.

PMID- 16443527
TI  - Endpoints for ablation of atrial fibrillation.

PMID- 16443528
TI  - Prospective comparison of echocardiographic atrioventricular delay optimization
      methods for cardiac resynchronization therapy.
AB  - BACKGROUND: Atrioventricular (AV) delay optimization can be an important
      determinant of the response to cardiac resynchronization therapy (CRT) in
      patients with medically refractory heart failure and a ventricular conduction
      delay. OBJECTIVES: The purpose of this study was to compare two Doppler
      echocardiographic methods of AV delay optimization after CRT. METHODS: Forty
      consecutive patients (age 59 +/- 12 years) with severe heart failure, New York
      Heart Association class 3.1 +/- 0.4, QRS duration 177 +/- 23 ms, and left
      ventricular ejection fraction 26% +/- 6% referred for CRT were studied using two
      dimensional Doppler echocardiography. In each patient, the acute improvement in
      stroke volume with CRT in response to two methods of AV delay optimization was
      compared. In the first method, the AV delay that produced the largest increase in
      the aortic velocity time integral (VTI) derived from continuous-wave Doppler
      (aortic VTI method) was measured. In the second method, the AV delay that
      optimized the timing of mitral valve closure to occur simultaneously with the
      onset of left ventricular systole was calculated from pulsed Doppler mitral
      waveforms at a short and long AV delay interval (mitral inflow method). RESULTS:
      The optimized AV delay determined by the aortic VTI method resulted in an
      increase in aortic VTI of 19% +/- 13% compared with an increase of 12% +/- 12% by
      the mitral inflow method (P <.001). The optimized AV delay by the aortic VTI
      method was significantly longer than the optimized AV delay calculated from the
      mitral inflow method (119 +/- 34 ms vs 95 +/- 24 ms, P <.001). There was no
      correlation in the AV delay determined by the two methods (r = 0.03). CONCLUSION:
      AV delay optimization by Doppler echocardiography for patients with severe heart
      failure treated with a CRT device yields a greater systolic improvement when
      guided by the aortic VTI method compared with the mitral inflow method.

PMID- 16443529
TI  - Development and testing of an algorithm to detect implantable cardioverter
      defibrillator lead failure.
AB  - BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead failures often
      present as inappropriate shock therapy. An algorithm that can reliably
      discriminate between ventricular tachyarrhythmias and noise due to lead failure
      may prevent patient discomfort and anxiety and avoid device-induced proarrhythmia
      by preventing inappropriate ICD shocks. OBJECTIVES: The goal of this analysis was
      to test an ICD tachycardia detection algorithm that differentiates noise due to
      lead failure from ventricular tachyarrhythmias. METHODS: We tested an algorithm
      that uses a measure of the ventricular intracardiac electrogram baseline to
      discriminate the sinus rhythm isoelectric line from the right ventricular coil
      can (i.e., far-field) electrogram during oversensing of noise caused by a lead
      failure. The baseline measure was defined as the product of the sum (mV) and
      standard deviation (mV) of the voltage samples for a 188-ms window centered on
      each sensed electrogram. If the minimum baseline measure of the last 12 beats was
      <0.35 mV-mV, then the detected rhythm was considered noise due to a lead failure.
      The first ICD-detected episode of lead failure and inappropriate detection from
      24 ICD patients with a pace/sense lead failure and all ventricular arrhythmias
      from 56 ICD patients without a lead failure were selected. The stored data were
      analyzed to determine the sensitivity and specificity of the algorithm to detect
      lead failures. RESULTS: The minimum baseline measure for the 24 lead failure
      episodes (0.28 +/- 0.34 mV-mV) was smaller than the 135 ventricular tachycardia
      (40.8 +/- 43.0 mV-mV, P <.0001) and 55 ventricular fibrillation episodes (19.1 +/
      22.8 mV-mV, P <.05). A minimum baseline <0.35 mV-mV threshold had a sensitivity
      of 83% (20/24) with a 100% (190/190) specificity. CONCLUSION: A baseline measure
      of the far-field electrogram had a high sensitivity and specificity to detect
      lead failure noise compared with ventricular tachycardia or fibrillation.

PMID- 16443530
TI  - Implantable cardioverter-defibrillators are still getting smarter: now a way to
      identify lead failure and prevent resultant inappropriate shocks.

PMID- 16443531
TI  - Predictors of success after selective pulmonary vein isolation of arrhythmogenic
      pulmonary veins for treatment of atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) ablation procedures typically involve
      isolation of all pulmonary veins (PVs) in addition to adjunctive linear lesions,
      yet the need for such an extensive ablation strategy in all patients is unclear.
      OBJECTIVES: The purpose of this study was to identify a subgroup of patients
      undergoing AF ablation with good clinical success after limited PV isolation.
      METHODS: Patients (N = 450) underwent trigger-guided segmental isolation of only
      arrhythmogenic PVs. We compared clinical characteristics of patients who required
      isolation of only one or two PVs to those in whom AF ablation required isolating
      > or = 3 PVs. RESULTS: For the group of patients undergoing isolation of < or = 2
      PVs, AF freedom without antiarrhythmic drug use was achieved in 56 (58%) of 97
      patients, and AF control was achieved in 66 (68%) of 97 patients after a single
      procedure. After additional procedures, 77 (79%) of 97 patients achieved complete
      AF freedom without antiarrhythmic drugs, and 82 (85%) of 97 patients achieved AF
      control. Younger age (odds ratio [OR] 1.05; confidence interval [CI] 1.01,1.09)
      and lack of persistent AF (OR 3.27; CI 1.0, 10.7) were each independent
      predictors of freedom from AF. In patients younger than 50 years with paroxysmal
      AF undergoing isolation of < or = 2 PVs (n = 44), AF freedom without
      antiarrhythmic drugs was achieved in 32 (73%) of 44 after a single ablation
      procedure. CONCLUSION: Targeted PV isolation has a good long-term (18-month)
      success rate in patients younger than 50 years with paroxysmal AF and < or = 2
      PVs triggering AF.

PMID- 16443532
TI  - Endocardial impedance mapping during circumferential pulmonary vein ablation of
      atrial fibrillation differentiates between atrial and venous tissue.
AB  - BACKGROUND: Circumferential pulmonary vein ablation (CPVA) is an effective
      treatment for atrial fibrillation (AF). Accurate left atrial (LA) mapping is
      essential for creating lesions at the LA-pulmonary vein (PV) junction, avoiding
      PV stenosis. OBJECTIVES: The purpose of this study was to establish whether
      endocardial impedance varies within the LA and PVs and whether it is a useful
      tool for mapping and ablation. METHODS: Pilot Phase: Three-dimensional LA maps
      were created using CARTO. Impedance (Z) was measured using a radiofrequency
      generator at multiple points in the LA, PV ostia (PVO), and deep PVs in 79
      patients undergoing their first AF ablation (group 1) and 29 patients undergoing
      repeat CPVA (group 2). Prospective Phase: In an additional 20 patients, using
      pilot phase data, one operator defined catheter tip location as either LA or PVO
      based on CARTO and fluoroscopy. A second operator blinded to CARTO simultaneously
      did the same based on impedance at 15 +/- 4 points per patient. RESULTS: Group 1:
      Z(LA) was 99.4 +/- 9.0 omega. Z(PVO) was higher (109.2 +/- 8.5 omega), rising
      further as the catheter advanced into deep PV (137 omega +/- 18). Z(PVO) differed
      from Z(LA) by 9 +/- 4 omega. Group 2 had a lower Z(LA) and Z(PVO) compared with
      group 1 (P <.05). Impedance monitoring differentiated between LA and PVO, with
      91% specificity and sensitivity, 96% positive predictive value, and 81% negative
      predictive value. At 3-month follow-up, no patients had evidence of PV stenosis
      on magnetic resonance imaging. CONCLUSION: Impedance mapping reliably identifies
      the LA-PV transitional zone, facilitating AF ablation, and its use is associated
      with a low incidence of PV stenosis.

PMID- 16443533
TI  - Myocardial ischemia lowers precordial thump efficacy: an inquiry into mechanisms
      using three-dimensional simulations.
AB  - BACKGROUND: Precordial thump is the first International Liaison Committee on
      Resuscitation-prescribed procedure for advanced life support in witnessed cardiac
      arrest. Success rates vary and, according to clinical evidence, are significantly
      reduced under ischemic conditions. OBJECTIVES: The purpose of this study was to
      elucidate the mechanisms involved in termination of ventricular tachycardia (VT)
      by precordial thump and its decreased rate of success in ischemia using a three
      dimensional realistic model of electrical behavior in the rabbit ventricles.
      METHODS: The electrophysiologic effect of precordial thump was represented by
      recruitment of mechanosensitive channels in the regions affected by precordial
      thump. In normoxia, precordial thump opened cation nonselective stretch-activated
      channels (SAC-NS, reversal potential -20 mV). In ischemia, precordial thump was
      assumed to additionally activate ATP-sensitive K+ (K(ATP)) channels (reversal
      potential -95 mV). Ten randomly selected cases of VT were used, and for each case
      the effect of precordial thump on VT was examined for normoxia and under ischemic
      conditions of varying severity. RESULTS: Precordial thump was found to have a 60%
      success rate in normoxia and 30% in ischemia. Results demonstrate that precordial
      thump-induced SAC-NS opening in normoxia reduced heterogeneity in transmembrane
      potential by partially repolarizing excited tissue and depolarizing resting
      myocardium, potentially causing foci of excitation that eradicate the excitable
      gap, thus facilitating VT termination. Decreased precordial thump efficacy in
      ischemia was caused by recruitment of K(ATP), which diminished the depolarizing
      effect of SAC-NS on resting tissue and caused pronounced action potential
      shortening, thus facilitating establishment of reentry. CONCLUSION: This study
      provides mechanistic insight into precordial thump mechanisms and its reduced
      clinical utility in patients with myocardial ischemia.

PMID- 16443534
TI  - Precordial thump and commotio cordis: the yin and yang of mechanoelectric
      feedback in the heart.

PMID- 16443536
TI  - Ablation of ventricular tachycardia: does anyone have any new ideas?

PMID- 16443535
TI  - Characterization of the infarct substrate and ventricular tachycardia circuits
      with noncontact unipolar mapping in a porcine model of myocardial infarction.
AB  - BACKGROUND: Conventional mapping of ventricular tachycardia (VT) after myocardial
      infarction is limited in patients with hemodynamically untolerated or
      noninducible VT. OBJECTIVES: The purpose of this study was to develop a unique
      strategy using noncontact unipolar mapping to define infarct substrate and VT
      circuits. METHODS: Dynamic substrate mapping (DSM) was performed in seven pigs
      with healed anterior myocardial infarction. This technique defined substrate as
      the intersection of low-voltage areas identified in sinus rhythm and during
      pacing around the infarct. Pacing was also performed within the substrate to
      determine exit sites. RESULTS: Anteroapical transmural scar was identified in all
      animals. A mean of three pacing sites was used for substrate definition. The mean
      area (+/- SD) was 18.4 +/- 8.8 cm2 by DSM and 15.4 +/- 6.9 cm2 by pathology (P
      >.5). A mean of 4.5 sites was paced within substrate. Ten of 18 paced wavefronts
      exited substrate adjacent to the pacing area, seven exited at distant areas, and
      one had two exits. VT was induced in five animals (1.6 morphologies per animal).
      Except for one VT, circuit exit sites were identified at substrate borders on the
      endocardium. VT exit sites were at (n = 6) or near (n = 3) a pacing exit site.
      Electrogram voltages differed significantly between substrate, border, and
      nonsubstrate areas in infarcted animals and in comparison with control animals.
      No substrate was identified in two control animals. CONCLUSION: DSM is a reliable
      method for infarct substrate localization in this model. Pacing within substrate
      can predict VT exit sites and may prove useful for ablation of unmappable VT
      after myocardial infarction.

PMID- 16443537
TI  - Experimental model for paroxysmal atrial fibrillation arising at the pulmonary
      vein-atrial junctions.
AB  - BACKGROUND: The mechanism(s) by which pulmonary veins (PVs) become ectopically
      active and subsequently initiate and sustain atrial fibrillation (AF) remains
      poorly understood. OBJECTIVES: The purpose of this study was to produce an acute
      canine model of paroxysmal AF arising from the PVs. METHODS: In 11 dogs, a
      thoracotomy was performed and a 26-gauge needle with a polyethylene tube attached
      was inserted into a fat pad containing autonomic ganglia at the base of the PV.
      The 11 dogs were divided into two groups: acetylcholine (ACh) 1-10 mM (group I, n
      = 5) or carbachol (CARB) 1-10 mM (group II, n = 6) injected (0.5 mL) into the fat
      pad. RESULTS: Within 2 to 5 minutes after injection of parasympathomimetics into
      the fat pad, a sequence of heart rate slowing, spontaneous premature
      depolarizations, and spontaneous AF was observed in four of 11 dogs. In seven
      dogs, single premature extrastimuli easily induced AF. AF was sustained for an
      average of 10 minutes (ACh) and 38 minutes (CARB), with the shortest AF cycle
      length seen at the PV-atrial junction adjacent to the fat pad (AF cycle length 75
      +/- 41 ms for ACh and 37 +/- 12 ms for CARB). CONCLUSION: Acute autonomic
      remodeling produced by injection of parasympathomimetics into the fat pad
      resulted in spontaneous or easily induced sustained AF with short AF cycle
      length; the most rapid firing rate was observed in the PV and atria adjacent to
      the injected fat pad. These findings resemble paroxysmal AF in patients,
      suggesting that hyperactive autonomic ganglia may be a critical element in
      patients exhibiting focal AF arising from the PV.

PMID- 16443538
TI  - Paroxysmal atrial fibrillation: just a matter of nerves?

PMID- 16443539
TI  - Concealed conduction in nodal dual pathways: depressed conduction, prolonged
      refractoriness, or reset excitability cycle?
AB  - BACKGROUND: Concealed conduction is recognized as a major determinant of
      atrioventricular (AV) nodal filtering properties, but little is known about the
      underlying mechanisms. OBJECTIVES: The purpose of this study was to consistently
      elicit concealed conduction through the AV node and to determine the involvement
      of slow and fast pathways in resultant changes in nodal function. METHODS: The
      concealment zone (nodal effective refractory period minus nodal functional
      refractory period of atrium) was determined in six rabbit heart preparations with
      and without a conditioning cycle (10 ms longer than nodal effective refractory
      period). Nodal function curves were constructed for concealed cycle lengths
      selected within the concealment zone. Experiments were repeated after slow
      pathway ablation. RESULTS: When assessed with a blocked beat alone, a narrow
      concealment zone (22 +/- 12 ms, n = 3) was observed in 50% of the preparations.
      In contrast, when assessed with a blocked beat preceded by a conducted
      conditioning beat, a wider concealment zone (77 +/- 47 ms, n = 6, P <.03) was
      observed in all preparations. Increases in the concealed cycle length resulted in
      graded increases in the nodal effective refractory period and nodal functional
      refractory period and graded rightward shifts of the recovery curve as a whole,
      consistent with resetting of the excitability cycle in the slow and fast
      pathways. These effects were analogous to those expected from a conducted beat.
      Slow pathway ablation widened the concealment zone but failed to alter fast
      pathway resetting. CONCLUSION: Our approach reveals a wide concealment zone
      consistently displayed in all preparations. Concealed conduction acts as a
      resetting mechanism of the excitability cycle in the slow and fast pathways
      similar to that expected from a conducted beat.

PMID- 16443540
TI  - Temporary placement of a defibrillating lead in the treatment of infection and
      ventricular tachycardia.

PMID- 16443541
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy: screening, diagnosis,
      and treatment.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a heart
      muscle disorder characterized pathologically by fatty or fibrofatty replacement
      and electrical instability of the right ventricular myocardium. Clinical
      manifestations include structural and functional malformations (fatty
      infiltration, dilatation, aneurysms) of the right ventricle, ECG abnormalities,
      and presentation with ventricular tachycardias with left bundle branch block
      pattern or sudden death. The disease often is familial with an autosomal
      inheritance. The typical hallmarks of ARVD/C are distributed in the so-called
      "triangle of dysplasia." The functional and morphologic characteristics are
      relevant to clinical imaging approaches such as contrast angiography,
      echocardiography, radionuclide angiography, ultrafast computed tomography, and
      cardiovascular magnetic resonance imaging. Evident forms of the disease are
      straightforward to diagnose based on a series of diagnostic criteria proposed by
      the International Task Force for Cardiomyopathy. However, the diagnosis of early
      and mild forms of the disease often is difficult. Treatment is directed toward
      preventing life-threatening ventricular arrhythmias in which radiofrequency
      ablation and implantable defibrillators play an increasing role. Despite new
      diagnostic and therapeutic approaches in ARVD/C, uncertainties about the etiology
      of the disease, the genetic basis, the appropriate diagnosis and therapy, and the
      clinical course of patients with ARVD/C have resulted in several registries to
      increase our knowledge of this intriguing disease.

PMID- 16443542
TI  - Emerging paradigms of the epidemiology and demographics of sudden cardiac arrest.

PMID- 16443543
TI  - How to interpret electroanatomic maps.

PMID- 16443544
TI  - Voltage-calcium state-space dynamics during initiation of reentry.

PMID- 16443546
TI  - CD4+CD3- cells regulate the organization of lymphoid tissue and T-cell memory for
      antibody responses.
AB  - This review highlights the role of a CD4(+)CD3(-) accessory cell in the
      development of organized lymphoid infrastructures as well as in the development
      of high-affinity antibody responses and T-cell memory. These 2 functions are
      linked in the development of the vertebrate immune system and are effected by the
      constitutive expression of 2 sets of tumor necrosis factor (TNF) family members.
      The expression of lymphotoxin 3 (LT3), LT3, and TNF-3, which are closely linked
      genetically, affects the organization of lymphoid structures into B-cell and T
      cell areas; the dual expression of OX40 ligand (TNFSF4) and CD30 ligand (TNFSF8)
      influences both the survival of T-cells within germinal centers and T-cell
      memory.

PMID- 16443549
TI  - Consensus guideline for diagnosis and treatment of childhood idiopathic
      thrombocytopenic purpura.
AB  - A practice guideline aimed at standardizing the treatment for childhood
      idiopathic thrombocytopenic purpura (ITP) is presented. This consensus guideline
      is based on a survey carried out via a questionnaire prepared by the ITP
      Committee of the Japanese Society of Pediatric Hematology and sent to society
      members. The survey questionnaire included questions on the diagnosis of ITP
      submitted for the purpose of revising the ITP diagnostic guideline prepared in
      1990 by the Research Group for Intractable Hematopoietic Disorders; a revised
      diagnostic guideline also is presented.

PMID- 16443547
TI  - Roles of OX40 in the pathogenesis and the control of diseases.
AB  - OX40 belongs to the tumor necrosis factor receptor superfamily, and its
      expression is restricted to activated T-cells. Ligation of OX40 during T-cell
      dendritic cell interaction is crucial for clonal expansion of antigen-specific T
      cells and generation of T-cell memory. The ligand of OX40 (OX40L) is expressed
      not only on dendritic cells but also on other cell types, such as B-cells,
      vascular endothelial cells, natural killer cells, and mast cells. The
      pathophysiological relevance of this broad distribution needs further
      investigation. In particular, OX40L on vascular endothelial cells may play a role
      in inflammatory vasculitis as well as in atherosclerotic change. Recent studies
      with animal models have indicated the critical involvement of OX40 in the
      pathogenesis of a variety of immunologic abnormalities of inflammatory,
      autoimmune, infectious, allergic, and allotransplantation-related diseases.
      Blockade of OX40-OX40L interaction has been shown to prevent, cure, or ameliorate
      these diseases. In contrast, activation of OX40 is known to break an existing
      state of tolerance in malignancies, leading to a reactivation of antitumor
      immunity. These findings clearly suggest that the OX40/OX40L system is one of the
      most promising targets of immune intervention for treatment of these diseases.

PMID- 16443548
TI  - Immunotherapy targeting 4-1BB and its ligand.
AB  - T-cell activation in the absence of costimulation is futile because T-cells
      deprived of costimulatory signals enter a state of unresponsiveness or anergy.
      The interaction of 4-1BB and 4-1BB ligand (4-1BBL) activates an important
      costimulatory pathway with diverse and important roles in immune regulation.
      Signals relayed through 4-1BB generate strong CD8(+) T-cell responses rather than
      CD4(+) T-cell responses; this action results in cytokine induction and promotes T
      cell survival. In recent years, 4-1BB-mediated immune regulation has gained great
      significance because of the seemingly contradictory dual roles of agonistic anti
      4-1BB in vivo disease models. To date, agonistic 4-1BB monoclonal antibody has
      shown therapeutic potential against a variety of tumors, CD4(+) T-cell-mediated
      autoimmune diseases, and chronic graft-versus-host disease. In addition, blockade
      of 4-1BB/4-1BBL interaction has produced therapeutic effects against
      coxsackievirus-induced myocardial inflammation, herpetic stromal keratitis, and
      graft rejection. We propose that the dual roles of agonistic anti-4-1BB--an
      enhanced effector function and a suppressor function--are mediated by a novel
      CD11c(+)CD8(+) T-cell population.

PMID- 16443550
TI  - An increase in MPC-1- and MPC-1-CD45+ immature myeloma cells in the progressive
      states of bone marrow plasmacytosis: the revised phenotypic classification of
      monoclonal marrow plasmacytosis (MOMP-2005).
AB  - The heterogeneity of bone marrow plasmacytosis is clearly analyzed by multicolor
      staining with anti-CD38 antibody. To date, at least 5 subpopulations of plasma
      cells have been identified in the bone marrow of multiple myeloma (MM) patients
      with regard to the expression of MPC-1, CD49e (VLA-5), and CD45: MPC-1(-)CD49e(
      )CD45(+) proliferative immature cells, MPC-1(-)CD49e(-)CD45(-) immature myeloma
      cells, MPC-1(+)CD49e(-)CD45(-) and MPC-1(+)CD49e(-)CD45(+) intermediate myeloma
      cells, and MPC-1(+)CD49e(+)CD45(+) mature myeloma cells. We performed phenotypic
      analyses in 75 cases of monoclonal bone marrow plasmacytosis, including 46 cases
      of MM and 29 cases of monoclonal gammopathy of undetermined significance (MGUS).
      In 31 cases of progressive MM disease, MPC-1(-) immature and MPC-1(-)CD45(+)
      proliferative immature myeloma cells were significantly increased up to >25% and
      >10%, respectively, of the plasma cell fractions (CD38(++) cells), whereas there
      were no increases in MPC-1(-) or MPC-1(-)CD45(+) proliferative immature myeloma
      cells in 15 cases of stable disease. Interestingly, the proportions of MPC-1(-)
      and MPC-1(-)CD45(+) immature monoclonal plasma cells also increased in the 7
      progressive cases of MGUS. Finally, we present the revised (2005) phenotypic
      classification of monoclonal marrow plasmacytosis (MOMP-2005).

PMID- 16443545
TI  - Tumor necrosis factor/tumor necrosis factor receptor family members that
      positively regulate immunity.
AB  - The interactions between members of the tumor necrosis factor (TNF) family and
      their specific receptors (TNFRs) are influential in controlling cell division,
      life, and death. Recent evidence suggests that these interactions control the
      functionality and longevity of many types of cells involved in immune responses.
      In particular, it has become evident that certain interactions support the clonal
      expansion and survival of T-cells, B-cells, and dendritic cells and thus are
      essential for establishing a robust immune response. This review describes select
      TNF/TNFR family members that principally support activation and survival and
      prevent excessive cell death of T-cells (OX40L/OX40, 4-1BBL/4-1BB, CD30L/CD30,
      LIGHT/HVEM, CD70/CD27, and GITRL/GITR), B-cells (BAFF/BAFFR), and dendritic cells
      (RANKL/RANK). Expression of these ligands and receptors on the cell surface is
      highly regulated, and communication via them occurs during contact between T
      cells and dendritic cells and between T-cells and B-cells. The functional dynamic
      between these TNF/TNFR members is slowly being unraveled, including whether these
      molecules act together or sequentially or control different type of immune
      responses. This review summarizes aspects of these TNF/TNFR interactions that are
      potentially important to immune responses.

PMID- 16443551
TI  - Use of a B-type natriuretic peptide in evaluating the treatment response of a
      relapsed lymphoma with cardiac involvement.
AB  - A 50-year-old woman received a diagnosis of diffuse large B-cell non-Hodgkin's
      lymphoma in 2000 and achieved complete remission. In April 2004, echocardiography
      and computed tomography examinations identified a tumor attached to the tricuspid
      valve and protruding within the right atrium. Bone marrow and lymph node biopsies
      showed a relapse of large cell lymphoma. The patient had a markedly elevated
      level of B-type natriuretic peptide (BNP) but a normal level of cardiac troponin
      I. The follow-up evaluation of the BNP level after chemotherapy showed that it
      had returned to within normal limits, and an echocardiogram showed regression of
      the tumor. Use of the BNP level as a monitor in the treatment of cardiac lymphoma
      has never been reported. This article is the first to report the use of BNP
      monitoring before and after chemotherapy to evaluate a patient with an unusual
      relapsed lymphoma with cardiac involvement.

PMID- 16443552
TI  - Reversible Epstein-Barr virus-negative lymphadenopathy and bone marrow involved
      by Hodgkin's lymphoma in a rheumatoid arthritis patient undergoing long-term
      treatment with low-dose methotrexate: a case report and review of the literature.
AB  - We report a case of spontaneous regression of Epstein-Barr virus (EBV)-negative
      methotrexate-associated lymphadenopathy occurring with Hodgkin's lymphoma in the
      bone marrow of a 48-year-old woman with rheumatoid arthritis. Following 10 years
      of treatment with low-dose methotrexate, the patient developed pancytopenia,
      hypercalcemia, and elevated levels of liver enzymes over the course of 2 months.
      A computed tomography scan of the abdomen revealed splenomegaly and enlarged
      abdominal lymph nodes. A bone marrow biopsy demonstrated cellular marrow with 2
      paratrabecular granuloma-like lesions composed of histiocytes, fibroblasts, small
      lymphocytes, a few plasma cells, and scattered CD30(+)CD15(+) Hodgkin's cells,
      including a classic Reed-Sternberg cell. The results of EBV studies of the bone
      marrow were negative. Within a month from withdrawal of methotrexate treatment,
      the patient's symptoms and the abnormalities in the laboratory results had
      regressed completely. A positron emission tomography scan failed to detect
      lymphadenopathy. Twelve months later, the patient remains free of symptoms.

PMID- 16443553
TI  - A novel perforin gene mutation in a Japanese family with hemophagocytic
      lymphohistiocytosis.
AB  - A 4-month-old girl with clinical features of hemophagocytic lymphohistiocytosis
      (HLH) was successfully treated with immunochemotherapy but died at the age of 1
      year and 3 months, before hematopoietic stem cell transplantation could be
      performed. Her family history showed death during infancy of the eldest sister,
      suggesting a diagnosis of familial HLH (FHL). Direct sequencing of the DNA
      extracted from the patient's spleen tissue obtained at autopsy revealed a novel
      perforin gene mutation: a homozygous 1289G insertion (Asp430 frameshift and
      termination at amino acid residue 457), which has not previously been reported in
      FHL patients.

PMID- 16443554
TI  - A phase II study of VEPA/FEPP chemotherapy for aggressive lymphoma in elderly
      patients: Japan Clinical Oncology Group Study JCOG9203.
AB  - The Lymphoma Study Group (LSG) of the Japan Clinical Oncology Group conducted a
      phase II trial of LSG12 therapy for 45 elderly patients with aggressive lymphoma
      to clarify whether LSG12 reduces severe infection without lowering the complete
      response (CR) rate in comparison with LSG4. LSG12, which consisted of a regimen
      of vincristine, cyclophosphamide, prednisolone, doxorubicin, vindesine,
      etoposide, and procarbazine (VEPA/FEPP), excluded bleomycin and methotrexate of
      LSG4 therapy, reduced the dosages of doxorubicin and cyclophosphamide, and
      increased etoposide and procarbazine dosages instead. Inclusion criteria
      consisted of a patient age of 70 to 75 years, a World Health Organization
      performance status of 0 to 2, and acceptable organ function. The treatment was
      completed in 47% of the patients and terminated early for disease progression in
      20% and for toxicity in 16%. The CR rate was 60% (95% confidence interval [CI],
      44%-74%). The 5-year overall survival (OS) rate was 42% (95% CI, 27%-57%), and
      the median OS time was 4.3 years. Leukopenia of grade 3 to 4 occurred in 98% of
      the patients, and severe infection occurred in 9%. Eight patients with hepatitis
      C virus (HCV) antibody showed no severe hepatic toxicity and had a better CR or
      OS rate than the 37 HCV-negative patients. Although the outcomes of LSG12 met our
      expectations with a reduction in severe infection and equivalent CR and OS
      outcomes compared with LSG4 and CHOP (cyclophosphamide, doxorubicin, vincristine,
      and prednisolone), the possibility of a regimen more beneficial than LSG12 for
      aggressive lymphoma in the elderly patient should be explored because of frequent
      hematologic toxicity and poor compliance in LSG12.

PMID- 16443555
TI  - Intestinal diffuse large B-cell lymphoma associated with celiac disease: a
      Japanese case.
AB  - Intestinal non-Hodgkin's lymphoma (NHL), especially the T-cell type, is well
      known to be associated with celiac disease (CD), an enteropathic disorder with a
      propensity for certain racial and genetic backgrounds. CD is typically
      characterized by gastrointestinal (GI) symptoms, anti-transglutaminase antibodies
      in the sera, and microscopical findings of the intestinal mucosa, which resolve
      with a gluten-free diet (GFD). In Asian populations, including the Japanese, CD
      and the associated NHL have been supposed to be quite rare, and studies
      concerning the frequency of CD or its relationship with NHL are scarce. We
      describe a Japanese middle-aged man with intestinal diffuse large B-cell lymphoma
      associated with CD. Following multi-combined chemotherapy, the patient's lymphoma
      has been in a state of complete response, and his GI symptoms have improved with
      a GFD. This case suggests that the possibility of CD and its association with
      intestinal NHL should be kept in mind, even in Asian populations.

PMID- 16443556
TI  - Adoptive transfer of Epstein-Barr virus-specific cytotoxic T-lymphocytes for the
      treatment of angiocentric lymphomas.
AB  - Angiocentric lymphoma, known as natural killer (NK)/T-cell non-Hodgkin's
      lymphoma, has been reported to be associated with the Epstein-Barr virus (EBV).
      We performed adoptive transfer of EBV-specific polyclonal T-cell lines in 3
      patients with extranodal NK/T-cell lymphoma, nasal type, and evaluated the
      treatment for safety, immunologic reconstitution, and clinical outcomes. The
      tissue samples collected from the 3 patients were confirmed by polymerase chain
      reaction analysis to be EBV positive. In the cases of the first and second
      patients, EBV-transformed B-lymphoblastoid cell lines (LCLs) and T-cell lines
      were generated from peripheral lymphocytes of HLA-matched sibling donors. The
      third patient's T-cell lines were induced with autologous lymphocytes. Polyclonal
      T-cell infusion was carried out after high-dose radiotherapy because active
      relapsed disease remained in all of the patients. The first patient received 4
      weekly infusions of 2 3 10(7) cells/m(2), and the second and third patients
      underwent treatment with 2 cycles of infusions of the same dosage. All T-cell
      lines showed >60% NK activity, cytotoxic T-lymphocyte (CTL) responses of >40%
      against autologous LCLs, and no CTL activity against patient-derived
      lymphoblasts. The level of cytotoxicity increased substantially in all patients
      after cell infusion. The 2 patients who received T-cell therapy twice had
      stabilized disease for more than 3 years. These safe treatments exhibited no
      severe inflammatory response, and no serious toxicity developed during T-cell
      therapy. Our findings demonstrate that adoptively transferred cells may provide
      reconstitution of EBV-specific CTL responses in patients with active relapsed
      angiocentric lymphoma. These results provide a rationale for the immunotherapy of
      angiocentric lymphoma.

PMID- 16443557
TI  - Reduced-intensity conditioning followed by unrelated umbilical cord blood
      transplantation for advanced hematologic malignancies: rapid engraftment in bone
      marrow.
AB  - Reduced-intensity (RI) conditioning followed by cord blood transplantation (CBT)
      is a new treatment modality, but failure to engraft is a major concern. We
      describe 12 patients with advanced hematologic malignancies who underwent RI
      conditioning and CBT with a conditioning regimen consisting of 200 mg/m(2)
      fludarabine (Flu), 50 mg/kg cyclophosphamide (CY), and 3 Gy total body
      irradiation (TBI). Cyclosporin A and/or methotrexate were used for graft-versus
      host disease prophylaxis. Cord blood grafts were not mismatched for more than 2
      serologically defined HLA alleles but were later found by high-resolution DNA
      typing to be mismatched for 2 to 4 alleles in most cases. Short tandem repeat
      analysis of bone marrow cells at day 14 showed complete donor chimerism in 6 of
      the patients and mixed chimerism in 5, indicating rapid engraftment in the bone
      marrow, whereas the remaining patient experienced graft rejection. Neutrophil
      recovery was achieved at a median of day 17 (range, days 11-24) in 10 of the 11
      patients with marrow chimerism at day 14. Of these 10 patients, however,
      transplantation-related mortality within 100 days occurred in 4 patients who
      showed failed platelet recovery and a lack of durable engraftment. Overall
      survival and disease-free survival rates were 41.7% and 33.3%, respectively.
      These results show that CB mismatched at 2 to 4 HLA alleles and transplanted with
      the Flu/CY/3 Gy TBI regimen is able to engraft in the bone marrow as early as day
      14.

PMID- 16443558
TI  - Mycophenolate mofetil is effective and well tolerated in the treatment of
      refractory acute and chronic graft-versus-host disease.
AB  - We enrolled 11 patients with refractory graft-versus-host disease (GVHD) in a
      prospective trial evaluating the efficacy of mycophenolate mofetil (MMF). Four
      (67%) of the 6 patients with acute GVHD and all 5 patients with chronic GVHD
      responded to MMF. Ten (91%) of the 11 patients were able to decrease steroid use
      (median decrease, 86%; range, 25%-100%). After a median follow-up of 18 months
      (range, 1-65 months), 7 patients (64%) remained alive. The adverse events were
      infectious complications (36%), diarrhea (27%), and neutropenia (18%); the only
      patient discontinuing MMF did so because of grade 4 neutropenia. This preliminary
      study suggests that MMF is a well-tolerated agent and has a beneficial effect in
      the treatment of refractory acute and chronic GVHD.

PMID- 16443559
TI  - Influence of radiation dose rate and lung dose on interstitial pneumonitis after
      fractionated total body irradiation: acute parotitis may predict interstitial
      pneumonitis.
AB  - This study evaluated patients for the influence of the dose rate and lung dose of
      fractionated total body irradiation (TBI) in preparation for allogeneic bone
      marrow transplantation (BMT) on the subsequent development of interstitial
      pneumonitis (IP). Sixty-six patients at our institute were treated with TBI
      followed by BMT. All of the patients received a total TBI dose of 12 Gy given in
      6 fractions over 3 days and were divided into 3 groups according to the radiation
      dose rate and lung dose: group A, lung dose of 8 Gy (n = 18); group B, lung dose
      of 12 Gy at 8 cGy/min (n = 25); and group C, lung dose of 12 Gy at 19 cGy/min (n
      = 23). The overall survival rate, the cumulative incidence of relapse, and the
      cumulative incidence of IP were evaluated in relation to various potential
      indicators of future IP. There were no significant differences in survival and
      relapse rates between patient group A and combined groups B and C. Clinically
      significant IP occurred in 13 patients. The cumulative incidence of IP was
      significantly higher in patients who developed acute parotitis as indicated by
      either an elevation in the serum amylase level or parotid pain of grade 1 to 2.
      There was no difference in IP incidence among groups A, B, and C. There was no
      significant difference in IP incidence between lung dose values of 8 Gy (with
      lung shielding) and 12 Gy (without lung shielding) and between dose rate values
      of 8 cGy/min and 19 cGy/ min, at least when TBI was given in 6 fractions. The
      presence of acute parotitis during or just after TBI may be a predictor of IP.

PMID- 16443561
TI  - Salt sensitivity, anxiety, and irritability predict blood pressure increase over
      five years in healthy males.
AB  - Salt sensitivity and psychological factors are thought to be associated with a
      higher risk for the development of hypertension but data on the relation between
      age-related blood pressure increase and salt sensitivity or psychological factors
      are scarce. A total of 31 healthy young males who were previously classified with
      respect to salt sensitivity, mental stress reactivity, trait-anxiety, trait
      anger, and irritability were followed up 4.8 years later by 24 hr ambulatory
      blood pressure monitoring (ABP). Our results showed anxiety and irritability
      correlated significantly with 24-hr ABP 4.8 years later (p < 0.05). The increase
      of diastolic blood pressure over 4.8 years was higher in salt-sensitive than salt
      resistant subjects (p < 0.07). Heart rate and diastolic blood pressure correlated
      significantly with systolic and diastolic 24-hr ABP and blood pressure reactivity
      under mental stress with diastolic 24-hr ABP. A regression analysis that included
      cardiovascular and psychological factors yielded 34% (systolic ABP, p < 0.009)
      and 58% (diastolic ABP, p < 0.0001) of variance. We concluded that anxiety and
      irritability are important predictors of blood pressure increase over time in
      healthy males.

PMID- 16443563
TI  - Blood pressure control in patients with hypertension: a community-based study.
AB  - The objective of own study was to investigate the quality of hypertension
      management in a rural Chinese population. A prospective cross-sectional study was
      conducted in 922 hypertensive patients in a regional community in southern China.
      The average systolic (SBP) and diastolic blood pressure (DBP) was 167.8 +/- 22.5
      mmHg and 94.3 +/- 14.2 mmHg respectively. A total of 823 patients (89.3%)
      patients had a SBP of greater than or equal to 140 mmHg, and 596 (64.6%) had a
      DBP of greater than or equal to 90 mmHg. Fully 568 patients (69.7%) were treated
      with one or two antihypertensive drugs, mostly with calcium channel blockers. In
      patients treated with antihypertensive drugs, the average SBP and DBP were 170.3
      +/- 23.1 mmHg and 96.2 +/- 14.8 mmHg, respectively. Blood pressure was poorly
      controlled in these hypertensive patients. Further studies are required to
      identify the barriers to the effective management of uncontrolled hypertension in
      a rural setting.

PMID- 16443562
TI  - Enhanced angiotensin II-induced activation of Na+, K+-ATPase in the proximal
      tubules of obese Zucker rats.
AB  - Renal angiotensin II (AII) is suggested to play a role in the enhanced sodium
      reabsorption that causes a shift in pressure natriuresis in obesity related
      hypertension; however, the mechanism is not known. Therefore, to assess the
      influence of AII on tubular sodium transport, we determined the effect of AII on
      the Na+, K+-ATPase activity (NKA), an active transporter regulated by the AT1
      receptor activity, in the isolated proximal tubules of lean and obese Zucker
      rats. Also, we determined the levels of the tubular AT1 receptor and associated
      signal transducing G proteins, as the initial signaling components that mediate
      the effects of AII on Na+, K+-ATPase activity. In the isolated proximal tubules,
      AII produced greater stimulation of the NKA activity in obese compared with lean
      rats. Determination of the AT1 receptors by Scatchard analysis of the [125I] Sar
      Ang II binding and Western blot analysis in the basolateral (BLM) and brush
      border membrane (BBM) revealed a modest but significant increase (23%) in the AT1
      receptor number mainly in the BLM of obese compared with lean rats. The AII
      affinity for AT1 receptors, as determined by IC50 values of AII to displace
      [125I] Sar-Ang II binding in BLM and BBM were similar in lean and obese rats.
      Western blot analysis revealed significant increases in Gialpha1, Gialpha2,
      Gialpha3, and Gq/11alpha in BLM and Gialpha1, Gialpha3, and Gq/11alpha in BBM of
      obese as compared with lean rats. The increase in the levels of the AT1 receptor
      and G proteins, mainly in the BLM, may be contributing to the enhanced AII
      induced activation of NKA in the proximal tubules of obese rats. This phenomenon,
      in part, may be responsible for the increased sodium reabsorption and the
      development of hypertension in obese Zucker rats.

PMID- 16443564
TI  - G-protein beta3 subunit gene variant (C825T) is unlikely to have a significant
      influence on serum total cholesterol level in Japanese workers.
AB  - We investigated the association between hypercholesterolemia or serum total
      cholesterol level and the C825T polymorphism in the G-protein ss3 subunit gene in
      Japanese workers using multivariate analysis to control possible confounding
      factors. The study subjects were 1,452 males and 1,169 females selected from
      3,834 males and 2,591 females. Hypercholesterolemia was classified as either a
      total serum cholesterol $5.7 mmol/L (220 mg/dL) or taking lipid-lowering
      medication. The statistical power of the study was estimated as 99.9% based on
      total cholesterol levels of previous significant studies in Caucasians and
      Japanese. The genotype distributions in males with hypercholesterolemia (CC = 78,
      CT = 154, TT = 78) and females (CC = 60, CT = 137, TT = 52) were not
      significantly different from normal males (CC = 280, CT = 595, TT = 267) or
      females (CC = 234, CT = 501, TT = 185). Allele distributions also were not
      significantly different in either sex. Logistic regression analysis of
      hypercholesterolemia data and analysis of variance, t-test and multiple
      regression of serum total cholesterol data demonstrated no significant
      relationship with the C825T genotype. Despite sufficient statistical power, this
      study did not demonstrate a significant influence of C825T on
      hypercholesterolemia or serum total cholesterol level. The targeting of this
      polymorphism therefore is unlikely to be beneficial in preventing
      hypercholesterolemia in the general Japanese population.

PMID- 16443567
TI  - "The orang lives almost next door" the correspondence between John Fulton (New
      Haven) and Willem Verhaart (Java).
AB  - Between 1937 and 1959 John Fulton (1899-1960), Sterling Professor of Physiology
      at Yale University (New Haven) and Willem Verhaart (1889-1983), neuropsychiatrist
      at Batavia Medical School (Java, Dutch East Indies) corresponded on
      neuroanatomical topics. Verhaart had easy access to primate brains in Batavia and
      stayed at Fulton's lab as a Rockefeller fellow (1938-1939), learning techniques
      of surgery and histology of the primate brain in order to apply it in his own
      lab. The correspondence relates of their undertakings in research, the
      preparations for Verhaart's stay in New Haven, the failure of subsequent research
      plans because of World War II, the camp experiences in Asia by Verhaart, the
      period of restoration after the war, helped by Fulton, and the political changes
      (independence) in Indonesia that finally lead to Verhaart's return to the
      Netherlands in 1950, where he became professor of histology and Director of the
      Neurological Institute at Leiden University. The correspondence shows how
      neuroscientists from different parts of the world cooperated. Moreover it is an
      example of the gradual change from a German (like his teacher Winkler) to an
      Anglo-American orientation in medical science that started in the beginning of
      the nineteenth century.

PMID- 16443565
TI  - Comparison of simultaneous measurements of blood pressure by tail-cuff and
      carotid arterial methods in conscious spontaneously hypertensive and Wistar-Kyoto
      rats.
AB  - We determined the validity of systolic blood pressure (SBP) measured by tail-cuff
      blood pressure (TCBP) with direct intra-arterial measurements. In conscious,
      restrained Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), carotid
      artery (CA) BP and TCBP were simultaneously measured. In both WKY and SHR
      strains, highly significant correlations between CABP and TCBP were found and
      Bland-Altman analyses showed no bias when the two methods were compared. The
      limits of agreement between CABP and TCBP in WKY and SHR were wide and
      reproducibility of pressure measurements by either technique was poor, with some
      evidence for strain-dependent differences. Pressure measurements made over short
      time frames, however, showed close agreement between CABP and TCBP. Acetylcholine
      induced reductions in pressure were equivalently detected by tail-cuff and direct
      arterial measurement in both strains but angiotensin II-induced pressure
      elevations were over-estimated by tail-cuff in SHR. Telemetered SBP measurements
      in conscious rats were highly variable in a strain-dependent manner.

PMID- 16443568
TI  - Neuroanatomy in art: Leonardo da Vinci's Senso Comune.

PMID- 16443569
TI  - Neurognostics question: "America's composite photographer".

PMID- 16443570
TI  - Charcot in contemporary literature.
AB  - Charcot and his medical observations remain an enduring topic of scientific study
      in neurology, but he is also the topic of modern literary works. This essay
      examines the depiction of Jean-Martin Charcot (1825-1893) as a character in late
      twentieth-century literature as an index of the contemporary nonmedical literary
      public's interest in neurology and Charcot. It focuses on three contemporary
      works that involve Charcot as a central figure with comparison between primary
      source documents and the rendered context, character development, and plot lines
      of these literary works. The two French novels [Slumbers of Indiscretion and Dr.
      Charcot of the Salpetriere] and one American play [Augustine (Big Hysteria)]
      approach Charcot and neurology with differing levels of historical accuracy. All
      create a figure of authority, each with a different coloration of the balance
      between power and its abuse. Two focus almost exclusively on his work with
      hysteria and inaccurately amplify Charcot's concern with symbolic sexual conflict
      as the origin of hysteria and fictionalize more extensive interactions with Freud
      than historical documents support. The three works demonstrate that Charcot
      retains an enduring fascination with an enigmatic personality, a controversial
      career, and a pivotal role in the development of studies involving the brain and
      behavior. Neurologists should not look to these works as replacements for more
      seriously composed historical studies, but as enrichments anchored in the
      imaginative possibilities of Charcot and his fin de siecle era.

PMID- 16443571
TI  - On the energy cost of mental effort.
AB  - The discovery of the Law of Conservation of Energy in the 1840s had consequences
      for psychological theory. Does the process of thinking involve a novel form of
      energy that is not recognized by physical science? E. L. Youmans (1821-1887)
      argued that "mental operations are dependent upon material changes in the nervous
      system." Kurd Lasswitz (1848-1910) introduced the term "psychophysical energy,"
      based upon the electrical activity of the brain. At the beginning of the
      twentieth century Alfred Lehmann (1858-1921) claimed that intense mental effort
      leads to a net increase in oxygen utilization and regarded this as evidence of a
      specific psychic energy. His views were adopted and extended by Hans Berger (1873
      1941). F. G. Benedict (1870-1957), drawing upon extensive experience with balance
      experiments conducted on humans in large-scale respiration calorimeters,
      concluded that mental effort probably had no effect upon the brain's metabolism.
      Modern approaches to the problem make use of PET imaging, which detects local
      changes in glucose utilization by the brain during cognitive activity.

PMID- 16443573
TI  - A half-century of perpetuating Netter's anatomic error.
AB  - The 1953 drawing by Netter of the thalamus mistakenly placed the dorsolateral
      nucleus on the wrong side of the internal medullary lamina. This error has been
      perpetuated in the best known texts on neuroscience for over fifty years.

PMID- 16443574
TI  - Wilhelminian myelinated fibers-Theodor Kaes, myeloarchitectonics and the asylum
      Hamburg-Friedrichsberg 1890-1910.
AB  - Since the 1890s Theodor Kaes (1852-1913), then alienist at the Hamburg asylum
      Friedrichsberg, began to explore myeloarchitectonics. He was particularly
      interested in dementia paralytica and the fibers of the association system.
      Following Paul Flechsig (1847-1929) and Theodor Meynert (1833-1892), Kaes read
      class and ethnical hierarchies into myelinated fibers and so could "decipher" the
      hierarchical structure of Wilhelminian society in the brain. Since 1908 he was in
      a fierce dispute with Korbinian Brodmann (1868-1918) about the correctness of his
      measurements. The article depicts the life and work of Kaes against the backdrop
      of the development of German neurosciences around 1900.

PMID- 16443575
TI  - NEUROwords: nomenclature on communication between the median and ulnar nerves in
      the hand.

PMID- 16443576
TI  - Augmentative and alternative communication: exploring basic issues.

PMID- 16443577
TI  - Issues in AAC research: how much do we really understand?
AB  - PURPOSE: The purpose of this introductory paper is to provide some overview of
      and background to the issues that were raised at the Augmentative and Alternative
      Research Seminar in conjunction with the First Regional AAC conference on 23
      February 2004. A group of 45 AAC researchers and professionals convened for one
      day to discuss some basic research issues in AAC. This paper highlights themes
      and perspectives that emerged from the research seminar discussions. METHOD:
      Literature reviews and discussion are used to provide a historical perspective on
      some of the issues raised. Two focus areas were identified for the purpose of
      this introductory paper; firstly, terminological issues that arose and secondly
      common themes that emerged during the paper presentations, discussions and/or
      written papers. Terminological issues include a brief description of the field of
      AAC for the benefit of those readers who might not be familiar with the field,
      whereafter the discussion focuses on the use of the term "complex communication
      needs" as referring to individuals who use AAC, the differentiation between
      symbols, signs, symbols sets and systems as well as the terms verbal and
      nonverbal, pre-linguistic and non-symbolic. The common themes throughout the
      papers include a discussion on the importance of context in communication, the
      chicken and egg question (i.e., comprehension and production), issues on
      multimodality, descriptive strategies for understanding interaction, and the use
      of typical interaction as a framework for understanding AAC interaction.
      CONCLUSIONS: In reviewing some of the issues in the field it is apparent that the
      issues we face now and those faced in AAC during earlier years are similar,
      however the need for a stronger database is apparent as the approach towards
      evidence-based practice becomes more prominent. The move to understand the nature
      of complex relationships in interaction is highlighted, for example, the multiple
      associations between environment, comprehension as well as the use of multi-modal
      communication. Whilst it became evident that most of these issues need further
      research in relation to typical interactions, applications to the field of AAC
      are most challenging.

PMID- 16443578
TI  - Speech, language and aided communication: connections and questions in a
      developmental context.
AB  - PURPOSE: This discussion paper focuses on four potential complexities in the
      language development of children with severe congenital speech impairments, who
      use graphic symbols as a primary means of expression. METHOD: Some of the
      literature in relation to language development in aided communication is
      reviewed. RESULTS: Four potentially significant connections are discussed,
      relating to: (i) the features of graphic symbols; (ii) the complexity of multi
      modal communication; (iii) the impact of selection and production on the process
      of developing a language system; and (iv), the connection between development and
      learning. CONCLUSIONS: It is proposed that the connections outlined are of
      fundamental significance in guiding intervention planning and in supporting
      language development in ways that have theoretical coherence.

PMID- 16443580
TI  - Multimodality: a basis for augmentative and alternative communication-
      psycholinguistic, cognitive, and clinical/educational aspects.
AB  - PURPOSE: Message generating is a complex process involving a number of processes,
      including the selection of modes to use. When expressing a message, human
      communicators typically use a combination of modes. This phenomenon is often
      termed multimodality. This article explores the use of models that explain
      multimodality as an explanatory framework for augmentative and alternative
      communication (AAC). METHOD: Multimodality is analysed from a communication,
      psycholinguistic, and cognitive perspective. RESULTS: Theoretical and applied
      topics within AAC can be explained or described within the multimodality
      framework considering iconicity, simultaneous communication, lexical
      organization, and compatibility of communication modes. CONCLUSION: Consideration
      of multimodality is critical to understanding underlying processes in individuals
      who use AAC and individuals who interact with them.

PMID- 16443579
TI  - Comprehension: an overlooked component in augmented language development.
AB  - PURPOSE: Despite the importance of children's receptive skills as a foundation
      for later productive word use, the role of receptive language traditionally has
      received very limited attention since the focus in linguistic development has
      centered on language production. For children with significant developmental
      disabilities and communication impairments, augmented language systems have been
      devised as a tool both for language input and output. The role of both speech and
      symbol comprehension skills is emphasized in this paper. METHOD: Data collected
      from two longitudinal studies of children and youth with severe disabilities and
      limited speech serve as illustrations in this paper. The acquisition and use of
      the System for Augmenting Language (SAL) was studied in home and school settings.
      Communication behaviors of the children and youth and their communication
      partners were observed and language assessment measures were collected. RESULTS:
      Two patterns of symbol learning and achievement--beginning and advanced--were
      observed. Extant speech comprehension skills brought to the augmented language
      learning task impacted the participants' patterns of symbol learning and use.
      CONCLUSIONS: Though often overlooked, the importance of speech and symbol
      comprehension skills were underscored in the studies described. Future areas for
      research are identified.

PMID- 16443581
TI  - Studying interaction between children who do not use symbols in interaction and
      their parents within the family system--methodological challenges.
AB  - PURPOSE: To parents of children with profound multiple disabilities who do not
      use symbols in interaction a successful outcome of dyadic interaction with their
      children consists of shared experiences, mutual joy and understanding. In the
      last two decades interaction intervention for these parents and their children
      has become an issue for research with the aim to identify factors that facilitate
      mutually rewarding parent-child interaction. Interaction patterns between the
      child and his/her caregivers must be studied, assessed and intervened within
      relation to the family system and how it changes over time. The aim of this
      article is to discuss the methodological challenges in studying parent-child
      interaction in the context of the family system. METHOD: Research methods
      designed to handle complexity, multidimensionality, heterogeneity among research
      subjects and small number of participants in the analysis are described.
      CONCLUSIONS: It is concluded that the theories and methods used must guide the
      researcher in how to delimit a manageable number of factors to include in the
      analysis, in how to analyse the interrelationships between the factors, and in
      how to study changes in patterns of factors over time. Prerequisites to meet the
      methodological challenges are that the constructs investigated have a sound
      theoretical base and that longitudinal data are collected.

PMID- 16443582
TI  - Role of tunica albuginea in erection: is it a dynamic or a static role?
AB  - The tunica albuginea (TA) of the penis is claimed to share in erectile mechanism
      by compressing the emissary veins passing through it. Apparently this claim is
      theoretical as no experimental studies could be traced in literature proving this
      concept. We investigated the hypothesis that TA acts as a cover to corpora
      cavernosa (CC) and spongiosa (CS) and does not have an active role in erectile
      mechanism. Penises of 9 dogs were degloved and TA was divided at upper, middle
      and lower 1/3 of the penis. The intracorporal and glans penis (GP) pressures were
      measured in the TA-covered and non-covered parts of CC and CS in the flaccid and
      erectile phases. Sham operation, without performing the TA incisions, was done in
      7 control animals. In the test animals, intracorporal pressure (ICP) in the non
      TA covered corpora and in GP recorded in flaccid phase a mean of 12.2 +/- 0.8
      cmH2O for CC and 11.3 +/- 0.7 cmH2O for the CS and GP, and in the erectile phase
      98.4 +/- 8.6 and 76.2 +/- 9.3 cmH2O, respectively. There was no significant
      difference between covered and non-covered corpora or between test and control
      animals. In conclusion, the TA seems to act as a cover to the corporal tissue.
      Its absence did not change ICP.

PMID- 16443583
TI  - Chromosomal abnormalities in patients with azoospermia in Western Mexico.
AB  - In order to assess the frequency of chromosomal abnormalities in azoospermic
      males from western Mexico, we carried out a retrospective study in 227 patients.
      Forty-three (18.9%) cases with an abnormal karyotype were found. The most
      frequent chromosomal anomaly was 47,XXY, which was identified in 35 subjects
      (15.4%). In six cases (2.6%), structural aberrations were detected: two
      Robertsonian translocations [(45,XY,t(13;22)(p11;p11) and
      (45,XY,t(13;15)(p11;p11)], a Y;autosome translocation
      [46,XY,der(15)t(Y;15)(q12;p11)], and three mosaics [mos45,X/46,X,idic(Y)(q11)].
      In general, these findings are in accordance with those from other surveys and
      confirm that the XXY aneuploidy is the most frequent chromosomal abnormality in
      azoospermic individuals.

PMID- 16443584
TI  - Cytogenetic analyses in infertile men.
AB  - In order to assess the significance of chromosome abnormalities and polymorphic
      chromosomal variants in male infertility, the results of cytogenetic studies of
      90 patients (32 azoospermic and 58 oligozoospermic men) were compared with those
      of 30 control fertile men in Estonia. Total chromosome alterations were revealed
      in 47.8% of infertile men. Major chromosomal abnormalities had a 10-fold increase
      (13.4%) in infertile males (15.6% in azoospermics and 12% in oligozoospermics)
      compared to the control group. In azoospermics, the most prevalent were sex
      chromosomal abnormalities (47,XXY)(12%), whereas a Robertsonian translocation,
      t(13;14) was found in one patient (3.1). In contrast, in the oligospermia group
      the most frequent abnormalities were autosomal (10%), of which 6.9% were
      translocations. Sex chromosomal abnormalities were found very rarely (1.7%).
      Incidence of chromosomal variants was high (38%), but similar in all groups. The
      most frequently observed polymorphisms involved chromosome 9. In conclusion,
      chromosomal abnormalities found with a high frequency in infertile males are a
      major cause of male infertility, and justify the requirement of cytogenetic
      analysis in every infertile man.

PMID- 16443585
TI  - Effect of body weight on testosterone/estradiol ratio in oligozoospermic
      patients.
AB  - To evaluate the effect of body mass on the hormonal and semen profiles of
      subfertile men with oligozoospemia, sperm concentration and reproductive hormone
      levels were compared in two body mass index (BMI) groups: underweight or normal
      weight patients (BMI = 25 kg/m2) vs. overweight or obese patients (BMI > 25
      kg/m2). The mean BMI was 27 +/- 4.6 kg/m2. The testosterone/estradiol ratio was
      significantly reduced in the high BMI group as compared to the low BMI group (17
      +/- 4 vs. 12 +/- 3; p < 0.05). A similar difference was found in the sperm
      concentration (11.2 +/- 3.16 x 10(6)/ml vs. 8.1 +/- 2.6 x 10(6)/ml). A
      nonsignificant difference was found in the LH/FSH ratio (1.41 +/- 0.64 vs. 1.63
      +/- 0.72). We concluded that obesity and the consequent estrogen excess decrease
      the sperm concentration by influencing the hypothalamo-pituitary system.

PMID- 16443587
TI  - Effects of sense tankyrase transfection on smooth muscle cells of corpus
      cavernosum in rat.
AB  - This study was conducted to construct the eukaryotic expression vectors for sense
      tankyrase and to investigate the effects of tankyrase transfection on smooth
      muscle cells of corpus cavernosum in the rat. After the eukaryotic expression
      vectors for sense tankyrase were constructed and identified smooth muscle cells
      of rat corpus cavernosum were transfected with the recombinant plasmids of sense
      tankyrase (pcDNA-TNKS). Levels of DNA and RNA were then evaluated. Measurement of
      telomerase activity was conducted by TRAP-ELISA assay, the length of telomere by
      Southern blot and the growth curve by MTT assay. We have found that the
      eukaryotic expression vectors for sense tankyrase were constructed and the
      recombinant plasmids of sense tankyrase were transfected into smooth muscle cells
      of rat corpus cavernosum successfully; no significant differences in telomerase
      activity were observed between TNKS-transfected cells (SMC-TANKS), zero-load-
      transfected cells (SMC-Zeo), and non-transfected cells (SMC) (P > 0.05). The
      length of telomere in SMC-TANKS was longer than that in SMC-Zeo or SMC (P <
      0.01), and the OD value of TNKS-transfected cell was significantly higher than
      that of the non-transfected cells (P < 0.01). These results suggested that the
      eukaryotic expression vectors for sense tankyrase were constructed successfully,
      which provides the basis for gene therapy. Transfection of recombinant plasmids
      of sense tankyrase helps change the telomerase length of smooth muscle cells of
      corpus cavernosum and extend the cell life span.

PMID- 16443586
TI  - Cordyceps sinensis mycelium induces MA-10 mouse Leydig tumor cell apoptosis by
      activating the caspase-8 pathway and suppressing the NF-kappaB pathway.
AB  - Cordyceps sinensis has been used as nutritious food and medicine in Chinese
      society. CS can inhibit tumor growth and induce tumor cell apoptosis. CS induced
      MA-10 mouse Leydig tumor cell death, but the anti-tumor mechanisms are not fully
      understood. Thus, the aim of this study was to investigate the apoptotic effect
      of CS on MA-10 cells and determine the molecular mechanism. CS (2-10 mg/ml) was
      added to MA-10 cells at different time scales (0-24 h). The condensation of DNA
      chromatin and apoptotic nuclear fragmentation increased in CS-treated MA-10
      cells. Western blot analysis showed that 3 hours of CS treatment caused an
      increase in caspase-3 and -8 expressions only, which provided further evidence
      for the involvement of caspase-3 and -8 in CS-induced MA-10-cell apoptosis. CS
      blocked NF-?B protein expression in a dose-dependent relationship. CS induces MA
      10 cell apoptosis by activating caspase-8-dependent and caspase-9-independent
      pathways and downregulating NF-?B protein expression.

PMID- 16443588
TI  - Combination regimen in the treatment of chronic prostatitis.
AB  - The aim of the study was to report our experiences in the treatment of chronic
      prostatitis using combination regimen including ciprofloxacin, doxazosin,
      allopurinol and biofeedback perineal massage. From May 2003 to April 2004, 7
      patients with NIH Category II-chronic bacterial prostatitis and 7 patients with
      NIH Category IIIA-inflammatory chronic pelvic pain syndrome were treated. The NIH
      Chronic Prostatitis Symptom Index (NIH-CPSI) was scored by the patient before and
      after the treatment, 6 months later. In Category II patients, the bacterial
      eradication rate was 71% after ciprofloxacin treatment during a follow-up of 6
      months. The beneficial response rate to allopurinol, doxazosin and biofeedback
      perineal massage was 50%, 42% and 85%, respectively. In NIH Category IIIA
      patients, the individual beneficial response rate to ciprofloxacin, allopurinol,
      doxazosin and biofeedback perineal massage was 57%, 100%, 71% and 100%,
      respectively. Comparing pre-treatment and post-treatment results of the
      combination regimen, there was a statistically significant improvement in the 3
      domains of pain score, urinary symptoms and quality of life impact of the NIH
      CPSI. Combination regimen including ciprofloxacin, doxazosin allopurinol and
      biofeedback perineal massage in the treatment of chronic prostatitis is a safe
      and effective modality in our limited experience.

PMID- 16443589
TI  - Complications following combined transrectal ultrasound-guided prostate needle
      biopsies and transurethral resection of the prostate.
AB  - In order to evaluate safety and morbidity aspects of additional systematic
      prostate biopsies, we have conducted a retrospective review of patients who had
      undergone transurethral resection of the prostate (TUR-P) combined with
      additional systemic prostate needle biopsies at the Chang Gung Memorial Hospital.
      To this end, the records of 80 men presenting consecutively at our institution
      between February 2001 and January 2004 inclusively were examined. These 80
      individuals included patients experiencing obstructive voiding symptoms and those
      featuring suspicious screening parameters, all of whom were to undergo
      transurethral resection of the prostate for symptomatic benign prostatic
      hyperplasia (BPH), all procedures being performed by a single surgeon. A total of
      20 (25%) specimens were found to be positive for prostate cancer. Cancer was
      detected in the transrectal prostate biopsy specimen of 16 of 57 men (28%) who
      had not undergone a previous prostate biopsy, and for four of 23 (17%) who had
      undergone at least one previous (benign) biopsy. Mild complications associated
      with transurethral prostrate resection, such as hematuria and hemospermia, were
      reported frequently, featuring rates of 10% and 2.5%, respectively; more severe
      complications being noted far less frequently. Fever, usually of a low grade, was
      observed post-operatively for six (7.5%) patients, but a prompt return to normal
      temperature following antibiotic treatment for one day was revealed. Four (5%)
      patients remained admitted to the hospital for a prolonged period following
      surgery. A review of the literature concerning transrectal biopsies and TUR-P has
      shown that surgery-associated complication rates are slightly lower than was the
      case for our study. Additional systematic prostate biopsies for patients
      undergoing TUR-P would appear to be a relatively safe treatment procedure.
      Identification of risk factors for post-surgery complications might further
      improve the safety of the screening procedure.

PMID- 16443590
TI  - Quality of life in men with localized prostate cancer treated by radical
      prostatectomy or radiotherapy.
AB  - Radical prostatectomy and radiotherapy are the most commonly utilized modalities
      for managing patients with localized prostate cancer. Each has effects on quality
      of life that are important in decision making. Long term side effects of these
      treatment modalities include urinary, bowel and sexual dysfunction, and have been
      documented. Comparison of the side effects of these different modalities
      continues to be explored, emphasizing their effects on quality of life (QOL) from
      the patient's viewpoint. Questionnaires were mailed to 224 eligible patients and
      a response was elicited in 161 men (72%). The final number of patients who
      completed all the questionnaires was 151. Of these, 73 (48%) had radical
      prostatectomy and 78 (52%) had radiotherapy. General well being measures
      demonstrated a definite advantage favoring men treated with radical
      prostatectomy. Prostate cancer specific QOL measures were similar among men
      treated with surgery or radiotherapy. Radiotherapy treated men were slightly more
      likely to report bowel-related problems than surgically treated men. Urinary QOL
      measures were no different between treated groups. Surgically treated men
      reported lower level of sexual function than radiotherapy treated men.

PMID- 16443591
TI  - Recovery of spermatozoa after rFSH/hCG treatment, and subsequent ICSI/IVF, in a
      male with testicular atrophy due to severe congenital hypogonadotrophic
      hypogonadism.
AB  - A 47-year old man attending at an in vitro fertilization clinic for infertility
      was diagnosed with congenital idiopathic hypogonadotrophic hypogonadism. No
      palpable testes and no spermatozoa in the ejaculate were found.
      Endocrinologically serum FSH, LH and testosterone was undetectable. A
      retroperitoneal magnetic resonance imaging confirmed the testicular absence.
      rFSH/hCG treatment was initiated. At four months almond-sized testes had
      developed and puncture with testicular sperm extraction (TESE) showed occasional
      immobile spermatozoa. Six months after initiation of treatment occasional mobile
      spermatozoa in semen were successfully used for intracytoplasmic sperm injection
      (ICSI) and one oocyte was fertilized and transferred. After 12 months sperm count
      revealed 10(5) mobile spermatozoa and three oocytes were fertilized. The embryo
      transfers did not result in a clinical pregnancy. As far as we know, this is the
      first time that objectively diagnosed testes atrophy could be successfully
      treated with FSH/hCG.

PMID- 16443592
TI  - Ultrastructural changes on sperm after extracorporeal shock wave lithotripsy in
      patients with distal ureteral stone.
AB  - Theoretically, ESWL can cause several side effects on the male reproductive
      system. We determined here the long-term effects of ESWL on sperm with
      transmission electron microscopy (TEM) in patients with distal ureteral stone.
      Fifteen men with stones in the distal ureter applied to our clinic formed the
      group of study. The other 15 men with renal or upper ureter stones formed the
      group of control. The ESWL sessions, including maximum 19 kW energy level and
      3000 shock waves, were performed with Siemens Lithostar (electromagnetic; Siemens
      Medical Systems, Erlangen, Germany) lithotriptor. We examined the semen samples
      from all patients on the day before and 90 days after ESWL. The semen samples
      were examined with transmission electron microscopy (TEM) to detect
      ultrastructural changes on the day before and 90 days after ESWL. All the
      statistical analyses were realized with SPSS 10.0 (SPSS Inc., Chicago, USA)
      statistical package program. When the control and study groups were compared for
      initial and day 90 sperm concentration and motility, a significant decrease was
      found in the study group. Although there was no important anomaly in the control
      group, we determined some damage on sperm structure in 5 patients (33.3%) who are
      in the study group 3 months after ESWL. It can reduce sperm concentration and
      motility permanently. It can also cause severe ultrastructural defects on sperm
      after a long term period in patients with lower ureteral stone. Therefore, we
      suggest other treatment modalities for young men with distal ureteral stones to
      prevent the development of male infertility.

PMID- 16443593
TI  - Ecological correlates of neglect in infants and toddlers.
AB  - Infants and toddlers are more likely to be victims of neglect than any other form
      of maltreatment. Infants and toddlers are at highest risk of fatality because of
      maltreatment and experience behavioral, social, academic, medical, and cognitive
      consequences of neglect during their most formative years. Within an ecological
      framework, this study examines the correlates of the substantiation of neglect in
      children 0 to 36 months of age. Using an ex post facto design and a random sample
      of 148 child protective services cases, bivariate analysis revealed significant
      differences in families who were substantiated for neglect in the areas of child
      characteristics, home environment, social environment, caregiver, and
      maltreatment situations. Multivariate analysis found children who were
      substantiated for neglect were exposed to greater environmental dangers and had
      caregivers who had poor parenting skills. Implications for practice and future
      research are discussed.

PMID- 16443594
TI  - Islamophobia pre- and post-September 11th, 2001.
AB  - Although much academic research has addressed racism, religious discrimination
      has been largely ignored. The current study investigates levels of self-reported
      racial and religious discrimination in a sample of 222 British Muslims.
      Respondents indicate that following September 11th, 2001, levels of implicit or
      indirect discrimination rose by 82.6% and experiences of overt discrimination by
      76.3%. Thus, the current work demonstrates that major world events may affect not
      only stereotypes of minority groups but also prejudice toward minorities. Results
      suggest that religious affiliation may be a more meaningful predictor of
      prejudice than race or ethnicity. General Health Questionnaire scores indicate
      that 35.6% of participants likely suffered mental health problems, with
      significant associations between problem-indicative scores and reports of
      experiencing a specific abusive incident of September 11th-related abuse by
      respondents. The dearth of empirical work pertaining to religious discrimination
      and its effects is a cause for concern.

PMID- 16443595
TI  - Will words ever harm me?: escalation from verbal to physical abuse in sixth-grade
      classrooms.
AB  - Based on in-depth qualitative interviews, this article gives the opportunity to
      145 sixth graders to tell, in their own words, how they felt and reacted when
      verbally and emotionally abused by their classmates. Content analysis of
      interviews revealed gender differences in students' reactions to verbal
      aggression. Another interesting finding was the differentiation between verbally
      aggressive messages meant to be for fun from those that were not so meant based
      on (1) contextual cues, (2) other peers' reaction, and (3) the malleability of
      the personal features that were the topic of the attack. Observing friendly peers
      were found to play an important role in reducing tension and preventing the
      escalation of violence. However, when the verbally aggressive message targeted a
      permanent physical characteristic or the student's social or ethnic identity,
      then suffering, anger and humiliation legitimized the escalation from verbal to
      physical aggression for students of both genders.

PMID- 16443596
TI  - Increasing honest responding on cognitive distortions in child molesters: the
      bogus pipeline procedure.
AB  - Professionals conclude that child molesters (CMs) hold offense-supportive beliefs
      (or cognitive distortions) from CMs'questionnaire responses. Because
      questionnaires are easily faked, we asked 32 CMs to complete a cognitive
      distortion scale under standard conditions (Time 1). A week later (Time 2), the
      same CMs completed the scale again. This time, approximately one half of CMs were
      attached to a pseudo lie detector (a bogus pipeline), and the rest completed the
      scale again under standard conditions (controls). At Time 1, CMs showed low
      cognitive distortion scores, seeming to indicate that they were faking good. At
      Time 2, bogus pipeline CMs seemed to believe that the apparatus could detect
      lies. However, this did not encourage more distorted belief disclosure compared
      with (a) their own previous scores and (b) controls. Furthermore, the bogus
      pipeline appeared to reduce cognitive distortion endorsements. The results stand
      in marked contrast to the common view that most CMs hold distorted beliefs.

PMID- 16443597
TI  - Psychopathology in women arrested for domestic violence.
AB  - This study examined the prevalence of psychopathology among women arrested for
      violence and whether the experience of intimate partner violence (IPV) was
      associated with Axis I psychopathology. Women who were arrested for domestic
      violence perpetration and court referred to violence intervention programs (N=
      103) completed measures of IPV victimization, perpetration, and psychopathology.
      Results revealed high rates of posttraumatic stress disorder (PTSD), depression,
      generalized anxiety disorder (GAD), panic disorder, substance use disorders,
      borderline personality disorder, and antisocial personality disorder. Violence
      victimization was significantly associated with symptoms of psychopathology.
      Logistic regression analyses showed that sexual and psychological abuse by
      partners were associated with the presence of PTSD, depression, and GAD
      diagnoses. Results highlight the potential importance of the role of violence
      victimization in psychopathology. Results suggest that Axis I and Axis II
      psychopathology should routinely be assessed as part of violence intervention
      programs for women and that intervention programs could be improved by offering
      adjunct or integrated mental health treatment.

PMID- 16443598
TI  - Effect of psychopathy on physical aggression toward gay and heterosexual men.
AB  - The purpose of this investigation was to examine the effect of psychopathy on
      antigay aggression. Participants were 84 heterosexual men who competed in an
      aggression paradigm in which electric shocks were received from and administered
      to a randomly determined fictitious opponent (heterosexual male, gay male) during
      a competitive reaction time task. Aggression was operationalized as shock
      intensities administered to the opponent. Prior to the task, all participants
      completed measures of psychopathy, sexual prejudice, and state anger; viewed a
      male-male erotic video; and reported state anger a second time. After controlling
      for sexual prejudice, analyses revealed that psychopathy significantly predicted
      aggression toward the gay, but not the heterosexual, male confederate.
      Psychopathy was not associated with increases in anger in response to the erotic
      video. These findings indicate that psychopathy is a significant marker for
      antigay violence, though anger experienced in response to homosexuality does not
      seem to underlie this association.

PMID- 16443600
TI  - The lesser-known Mendel: his experiments on Hieracium.

PMID- 16443599
TI  - Associations among cruelty to animals, family conflict, and psychopathic traits
      in childhood.
AB  - Previous research has produced mixed findings on the role of child and family
      factors in the genesis of childhood cruelty. The authors examined the
      relationships of cruelty to animals to a range of child and family factors.
      First, the authors test the idea that cruelty is a callous aggression that will
      be more strongly associated with psychopathic (callous or unemotional, CU) traits
      than general externalizing problems. Second, the authors operationalize family
      problems as open conflict rather than parenting problems as used earlier. Results
      indicated that for both genders, CU traits were associated strongly with cruelty.
      For boys, externalizing problems also added prediction in regression analyses.
      Family conflict was not associated with cruelty for either. These results suggest
      that cruelty to animals may be an early manifestation of the subgroup of children
      developing conduct problems associated with traits of low empathy and callous
      disregard rather than the more common pathway of externalizing problems and
      parenting problems.

PMID- 16443601
TI  - Role of N-terminal familial mutations in prion protein fibrillization and prion
      amyloid propagation in vitro.
AB  - A self-perpetuating conformational conversion of the prion protein (PrP) is
      believed to underlie pathology and transmission of prion diseases. Here we
      explore the effects of N-terminal pathogenic mutations (P102L, P105L, A117V) and
      the residue 129 polymorphism on amyloid fibril formation by the human PrP
      fragment 23-144, an in vitro conversion model that can reproduce certain
      characteristics of prion replication such as strains and species barriers. We
      find that these amino acid substitutions neither affect PrP23-144
      amyloidogenicity nor introduce barriers to cross-seeding of soluble protein.
      However, the polymorphism strongly influences the conformation of the amyloid
      fibrils, as determined by infrared spectroscopy. Intriguingly, unlike
      conformational features governed by the critical amyloidogenic region of PrP23
      144 (residues 138-139), the structural features distinguishing Met-129 and Val
      129 PrP23-144 amyloid fibrils are not transmissible by cross-seeding. While based
      only on in vitro data, these findings provide fundamental insight into the
      mechanism of prion-based conformational transmission, indicating that only
      conformational features controlling seeding specificity (e.g. those in critical
      intermolecular contact sites of amyloid fibrils) are necessarily transmissible by
      cross-seeding; conformational traits in other parts of the PrP molecule may not
      be "heritable" from the amyloid template.

PMID- 16443602
TI  - WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain
      and induce mitochondrial permeabilization.
AB  - The induction of apoptosis by p53 in response to cellular stress is its most
      conserved function and crucial for p53 tumor suppression. We recently reported
      that p53 directly induces oligomerization of the BH1,2,3 effector protein Bak,
      leading to outer mitochondrial membrane permeabilization (OMMP) with release of
      apoptotic activator proteins. One important mechanism by which p53 achieves OMMP
      is by forming an inhibitory complex with the anti-apoptotic BclXL protein. In
      contrast, the p53 complex with the Bcl2 homolog has not been interrogated. Here
      we have undertaken a detailed characterization of the p53-Bcl2 interaction using
      structural, biophysical, and mutational analyses. We have identified the p53 DNA
      binding domain as the binding interface for Bcl2 using solution NMR. The affinity
      of the p53-Bcl2 complex was determined by surface plasmon resonance analysis
      (BIAcore) to have a dominant component KD 535 +/- 24 nm. Moreover, in contrast to
      wild type p53, endogenous missense mutants of p53 are unable to form complexes
      with endogenous Bcl2 in human cancer cells. Functionally, these mutants are all
      completely or strongly compromised in mediating OMMP, as measured by cytochrome c
      release from isolated mitochondria. These data implicate p53-Bcl2 complexes in
      contributing to the direct mitochondrial p53 pathway of apoptosis and further
      support the notion that the DNA binding domain of p53 is a dual function domain,
      mediating both its transactivation function and its direct mitochondrial
      apoptotic function.

PMID- 16443603
TI  - Alzheimer disease-specific conformation of hyperphosphorylated paired helical
      filament-Tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin
      conjugation.
AB  - One of the key pathological hallmarks of Alzheimer disease (AD) is the
      accumulation of paired helical filaments (PHFs) of hyperphosphorylated
      microtubule-associated protein Tau. Tandem mass spectrometry was employed to
      examine PHF-Tau post-translational modifications, in particular protein
      phosphorylation and ubiquitination, to shed light on their role in the early
      stages of Alzheimer disease. PHF-Tau from Alzheimer disease brain was affinity
      purified by MC1 monoclonal antibody to isolate a soluble fraction of PHF-Tau in a
      conformation unique to human AD brain. A large number of phosphorylation sites
      were identified by employing a data-dependent neutral loss algorithm to trigger
      MS3 scans of phosphopeptides. It was found that soluble PHF-Tau is ubiquitinated
      at its microtubule-binding domain at residues Lys-254, Lys-311, and Lys-353,
      suggesting that ubiquitination of PHF-Tau may be an earlier pathological event
      than previously thought and that ubiquitination could play a regulatory role in
      modulating the integrity of microtubules during the course of AD. Tandem mass
      spectrometry data for ubiquitin itself indicate that PHF-Tau is modified by three
      polyubiquitin linkages, at Lys-6, Lys-11, and Lys-48. Relative quantitative
      analysis indicates that Lys-48-linked polyubiquitination is the primary form of
      polyubiquitination with a minor portion of ubiquitin linked at Lys-6 and Lys-11.
      Because modification by Lys-48-linked polyubiquitin chains is known to serve as
      the essential means of targeting proteins for degradation by the ubiquitin
      proteasome system, and it has been reported that modification at Lys-6 inhibits
      ubiquitin-dependent protein degradation, a failure of the ubiquitin-proteasome
      system could play a role in initiating the formation of degradation-resistant PHF
      tangles.

PMID- 16443604
TI  - Synapsin I is a major endogenous substrate for protein L-isoaspartyl
      methyltransferase in mammalian brain.
AB  - The accumulation of potentially deleterious L-isoaspartyl linkages in proteins is
      prevented by the action of protein L-isoaspartyl O-methyltransferase, a widely
      distributed enzyme that is particularly active in mammalian brain.
      Methyltransferase-deficient (knock-out) mice exhibit greatly increased levels of
      isoaspartate and typically succumb to fatal epileptic seizures at 4-10 weeks of
      age. The link between isoaspartate accumulation and the neurological
      abnormalities of these mice is poorly understood. Here, we demonstrate that
      synapsin I from knock-out mice contains 0.9 +/- 0.3 mol of isoaspartate/mol of
      synapsin, whereas the levels in wild-type and heterozygous mice are undetectable.
      Transgenic mice that selectively express methyltransferase only in neurons show
      reduced levels of synapsin damage, and the degree of reduction correlates with
      the phenotype of these mice. Isoaspartate levels in synapsin from the knock-out
      mice are five to seven times greater than those in the average protein from brain
      cytosol or from a synaptic vesicle-enriched fraction. The isoaspartyl sites in
      synapsin from knock-out mice are efficiently repaired in vitro by incubation with
      purified methyltransferase and S-adenosyl-L-methionine. These findings
      demonstrate that synapsin I is a major substrate for the isoaspartyl
      methyltransferase in neurons and suggest that isoaspartate-related alterations in
      the function of presynaptic proteins may contribute to the neurological
      abnormalities of mice deficient in this enzyme.

PMID- 16443606
TI  - Prognostic value of coronary artery calcium screening in asymptomatic smokers and
      non-smokers.
AB  - AIMS: To determine the extent and prognostic significance of coronary artery
      calcium in asymptomatic smokers and non-smokers. Population data are available on
      the prognostic impact of smoking on atherosclerotic imaging measurements of the
      carotid and peripheral arteries. Limited data are available on the impact of
      cigarette smoking on the prognostic value of coronary calcium. METHODS AND
      RESULTS: A referred patient registry of 10,377 asymptomatic individuals (40% were
      current smokers) was followed for death from all-causes at 5 years. Univariable
      and multivariable Cox proportional hazard models were calculated to estimate time
      to all-cause mortality. Cumulative 5-year survival was 96.9 and 98.4% for smokers
      when compared with non-smokers (P < 0.0001). Using a stratified Cox proportional
      hazards survival analysis, survival for non-smokers ranged from 99.7 to 89.6%
      with calcium score of 0-10 and >1000 (P < 0.0001). In comparison, smokers had
      survival rates ranging from 99.5 to 81.4% for calcium score of 0-10 to >1000 (P <
      0.0001). When further evaluating the effect of age on prognosis by coronary
      calcium, there was an additive relationship between age and calcium that was
      exacerbated with smoking, resulting in higher relative risk ratios for older
      smokers with coronary calcium (P < 0.0001). For smokers <50 years of age, a
      calcium score >1000 was associated with a relative risk ratio that was elevated
      8.9-fold (P = 0.029). Thus, resulting in an expected reduction in life expectancy
      of 4.8 years for smokers <50 years of age with a calcium score >400 (P < 0.0001).
      CONCLUSION: The prognostic value of coronary artery calcium scoring was accurate
      in identifying a high-risk cohort of asymptomatic smokers and non-smokers. Young
      smokers with high-risk calcium scores have a four- to nine-fold increased risk of
      dying when compared with similarly aged non-smokers. When prospectively applied,
      evidence of a high-risk calcium score may be useful in educating patients as to
      their expected risk of dying over the next 5 years.

PMID- 16443605
TI  - A tryptophan neutral radical in the oxidized state of versatile peroxidase from
      Pleurotus eryngii: a combined multifrequency EPR and density functional theory
      study.
AB  - Versatile peroxidases are heme enzymes that combine catalytic properties of
      lignin peroxidases and manganese peroxidases, being able to oxidize Mn(2+) as
      well as phenolic and non-phenolic aromatic compounds in the absence of mediators.
      The catalytic process (initiated by hydrogen peroxide) is the same as in
      classical peroxidases, with the involvement of 2 oxidizing equivalents and the
      formation of the so-called Compound I. This latter state contains an oxoferryl
      center and an organic cation radical that can be located on either the porphyrin
      ring or a protein residue. In this study, a radical intermediate in the reaction
      of versatile peroxidase from the ligninolytic fungus Pleurotus eryngii with
      H(2)O(2) has been characterized by multifrequency (9.4 and 94 GHz) EPR and
      assigned to a tryptophan residue. Comparison of experimental data and density
      functional theory theoretical results strongly suggests the assignment to a
      tryptophan neutral radical, excluding the assignment to a tryptophan cation
      radical or a histidine radical. Based on the experimentally determined side chain
      orientation and comparison with a high resolution crystal structure, the
      tryptophan neutral radical can be assigned to Trp(164) as the site involved in
      long-range electron transfer for aromatic substrate oxidation.

PMID- 16443608
TI  - Effects of cardiac resynchronization therapy on disease progression in chronic
      heart failure.
AB  - Despite the alleviation of symptoms and longer survival conferred by
      pharmacological management of chronic congestive heart failure (CHF), this
      progressive syndrome remains associated with high morbidity and premature death.
      A new treatment of CHF should ideally alleviate symptoms, improve functional
      capacity, decrease mortality, and slow or reverse its progression without adding
      risks for the patient that outweighs the benefits. Growing evidence indicates
      that devices implanted to resynchronize ventricular contraction are a beneficial
      adjunct in the treatment of CHF. This review discusses the remodelling process,
      and its clinical and prognostic significance. We also discuss the impact of CRT,
      on remodelling and disease progression with a particular focus on patients with
      asymptomatic or mild heart failure (NYHA Class I-II).

PMID- 16443607
TI  - Effects of nebivolol in elderly heart failure patients with or without systolic
      left ventricular dysfunction: results of the SENIORS echocardiographic substudy.
AB  - AIMS: The SENIORS trial recently demonstrated that nebivolol reduces the
      composite risk of all-cause mortality and cardiovascular hospital admission in
      elderly patients with chronic heart failure and, importantly, that ejection
      fraction does not influence the clinical effects of nebivolol. An
      echocardiographic substudy was designed to evaluate the effects of nebivolol on
      systolic and diastolic left ventricular (LV) function in patients stratified
      according to the presence or absence of systolic LV dysfunction. METHODS AND
      RESULTS: The substudy randomized 112 patients in 29 European centres, of whom 104
      were evaluable for the study; 43 had an ejection fraction (EF) <or=35% and 61 had
      an EF>35%. LV end-systolic volume (ESV), EF, mitral valve E/A ratio, and E-wave
      deceleration time were assessed at baseline and after 12 months. Echocardiograms
      were submitted to a core laboratory to perform quantitative analysis in blinded
      condition. In the group with EF</=35%, nebivolol reduced ESV (adjusted difference
      between treatments 25.8 mL, 95%CI: -46.6; -5.0, P=0.016) and improved EF
      (adjusted difference between treatments 4.6%, 95%CI: 1.3;7.9, P=0.008); no
      changes were observed in the E/A ratio or E-wave deceleration time. In EF>35%
      group, no significant changes in either systolic or diastolic parameters were
      observed. CONCLUSION: In patients with heart failure and advanced systolic LV
      dysfunction, nebivolol reduces ventricular size and improves EF. The absence of
      detectable changes with standard echocardiography in patients with predominant
      diastolic heart failure questions the mechanism of benefit on morbidity/mortality
      in such patients.

PMID- 16443609
TI  - Beta-blockade in heart failure: adding SENIORS to the mix.

PMID- 16443610
TI  - "Catastrophic" pathways to smoking cessation: findings from national survey.
AB  - OBJECTIVE: To assess the extent to which the prevailing model of smoking
      cessation (that smokers typically prepare their attempts to stop smoking in
      advance and that doing so increases their chances of success) is correct. DESIGN:
      Cross sectional household survey. SETTING: England. PARTICIPANTS: 918 smokers who
      reported having made at least one quit attempt and 996 ex-smokers aged 16 and
      over. MAIN OUTCOME MEASURES: Whether the most recent quit attempt was planned in
      advance and whether quit attempts made at least six months before resulted in at
      least six months' abstinence. RESULTS: 48.6% of smokers reported that their most
      recent quit attempt was put into effect immediately the decision to quit was
      made. Unplanned quit attempts were more likely to succeed for at least six
      months: among respondents who had made a quit attempt between six months and five
      years previously the odds of success were 2.6 times higher (95% confidence
      interval 1.9 to 3.6) in unplanned attempts than in planned attempts; in quit
      attempts made 6-12 months previously the corresponding figure was 2.5 (1.4 to
      4.7). The differences remained after controlling for age, sex, and socioeconomic
      group. CONCLUSIONS: A model of the process of change based on "catastrophe
      theory" is proposed, in which smokers have varying levels of motivational
      "tension" to stop and then "triggers" in the environment result in a switch in
      motivational state. If that switch involves immediate renunciation of cigarettes,
      this can signal a more complete transformation than if it involves a plan to quit
      at some future point.

PMID- 16443612
TI  - Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women
      on adjuvant aromatase inhibitors.
AB  - BACKGROUND: Aromatase inhibitors (AI) are increasingly used in early breast
      cancer and there is a growing interest in associated long-term side-effects of
      profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis
      are often managed with vaginal estrogen preparations. These are generally
      perceived to result in minimal systemic absorption of estrogen. We followed serum
      estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels
      in seven postmenopausal women using vaginal estrogen preparations whilst on AIs
      for breast cancer. PATIENTS AND METHODS: Serum was analysed for estradiol, FSH
      and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal
      estradiol. Estradiol was measured on an assay specifically developed for
      measuring low levels in postmenopausal women. RESULTS: Serum estradiol levels
      rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72
      pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority
      (median 16 pmol/l) although significant further rises were seen in two women.
      CONCLUSIONS: The vaginal estradiol tablet Vagifem significantly raises systemic
      estradiol levels, at least in the short term. This reverses the estradiol
      suppression achieved by aromatase inhibitors in women with breast cancer and is
      contraindicated.

PMID- 16443611
TI  - Effect of hepatitis B immunisation in newborn infants of mothers positive for
      hepatitis B surface antigen: systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effects of hepatitis B vaccine and immunoglobulin in
      newborn infants of mothers positive for hepatitis B surface antigen. DESIGN:
      Systematic review and meta-analysis of randomised clinical trials. DATA SOURCES:
      Electronic databases and hand searches. REVIEW METHODS: Randomised clinical
      trials were assessed for methodological quality. Meta-analysis was undertaken on
      three outcomes: the relative risks of hepatitis B occurrence, antibody levels to
      hepatitis B surface antigen, and adverse events. RESULTS: 29 randomised clinical
      trials were identified, five of which were considered high quality. Only three
      trials reported inclusion of mothers negative for hepatitis B e antigen. Compared
      with placebo or no intervention, vaccination reduced the occurrence of hepatitis
      B (relative risk 0.28, 95% confidence interval 0.20 to 0.40; four trials). No
      significant difference in hepatitis B occurrence was found between recombinant
      vaccine and plasma derived vaccine (1.00, 0.71 to 1.42; four trials) and between
      high dose versus low dose vaccine (plasma derived vaccine 0.97, 0.55 to 1.68,
      three trials; recombinant vaccine 0.78, 0.31 to 1.94, one trial). Compared with
      placebo or no intervention, hepatitis B immunoglobulin or the combination of
      plasma derived vaccine and hepatitis B immunoglobulin reduced hepatitis B
      occurrence (immunoglobulin 0.50, 0.41 to 0.60, one trial; vaccine and
      immunoglobulin 0.08, 0.03 to 0.17, three trials). Compared with vaccine alone,
      vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (0.54,
      0.41 to 0.73; 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem
      safe, but few trials reported adverse events. CONCLUSION: Hepatitis B vaccine,
      hepatitis B immunoglobulin, and vaccine plus immunoglobulin prevent hepatitis B
      occurrence in newborn infants of mothers positive for hepatitis B surface
      antigen.

PMID- 16443613
TI  - Glucose and leucine kinetics in idiopathic ketotic hypoglycaemia.
AB  - AIMS: To investigate glucose and leucine kinetics in association with metabolic
      and endocrine investigations in children with ketotic hypoglycaemia (KH) in order
      to elucidate the underlying pathophysiology. METHODS: Prospective interventional
      study using stable isotope tracer in nine children (mean age 4.23 years, range
      0.9-9.8 years; seven males) with KH and 11 controls (mean age 4.57 years, range
      0.16-12.3 years; four males). RESULTS: Plasma insulin levels were significantly
      lower in KH compared to subjects in the non-KH group. Plasma ketone body levels
      were significantly higher in KH than in non-KH. Basal metabolic rate was
      significantly higher in subjects with KH (45.48+/-7.41 v 31.81+/-6.72
      kcal/kg/day) but the respiratory quotients were similar in both groups (KH v non
      KH, 0.84+/-0.05 v 0.8+/-0.04. Leucine oxidation rates were significantly lower in
      children with KH (12.25+/-6.25 v 31.96+/-8.59 micromol/kg/h). Hepatic glucose
      production rates were also significantly lower in KH (3.84+/-0.46 v 6.6+/-0.59
      mg/kg/min). CONCLUSIONS: KH is caused by a failure to sustain hepatic glucose
      production rather than by increased glucose oxidation rates. Energy demand is
      significantly increased, whereas leucine oxidation is reduced.

PMID- 16443614
TI  - Asthma severity and atopy: how clear is the relationship?
AB  - BACKGROUND: The relationship between asthma severity and atopy is complex. Many
      studies have failed to show significant relationships between clinical severity
      or lung function and markers of atopic sensitisation. AIM: To determine whether
      increasing asthma severity is related to atopic sensitisation in a population of
      children with asthma. METHODS: A total of 400 children (7-18 years) with asthma
      were recruited as part of a multicentre study of the genetics of asthma. Detailed
      phenotypic data were collected on all participants. Associations between measures
      of asthma severity and atopic sensitisation were sought using multilevel models
      allowing variation at the individual and family level. RESULTS: Children
      recruited to the study had a range of asthma severities, with just over a third
      having mild persistent asthma. The logarithm of total serum IgE was associated
      with increased asthma severity score, decreased FEV1, increased airways
      obstruction, risk of hospital admission, and inhaled steroid use. Increasing skin
      prick test reactivity to a panel of seven aeroallergens was associated with
      increased risk of hospital admission, use of an inhaled steroid, and airways
      obstruction. The results remained highly significant after corrections for age,
      gender, and birth order. CONCLUSIONS: In children with asthma, increasing atopy
      is associated with increasing asthma severity. However, the relationships between
      asthma severity and skin prick tests, and asthma severity and total serum IgE
      values, appear subtly different.

PMID- 16443615
TI  - A prospective questionnaire assessment of attitudes and experiences of off label
      prescribing among hospital based paediatricians.
AB  - OBJECTIVE: To assess current attitudes of hospital based paediatricians to off
      label prescribing, and the performance of clinical trials in children. DESIGN: A
      prospective, questionnaire based study. SETTING: 257 hospital based consultants
      and specialist registrars in paediatric practice in Scotland during 2003-2004.
      RESULTS: A 25 item questionnaire was sent to 257 hospital based paediatricians
      and 151 (59%) were returned completed. Over 90% of responders were familiar with
      the concept of, and knowingly prescribed, off label drugs; 55% of responders
      stated that such prescribing disadvantaged children, and 47% expressed concerns
      about the efficacy of off label medicines. Although 70% of responders expressed
      concerns about safety, only 17% had observed an adverse event, and 47% a
      treatment failure, while 69% did not obtain informed consent or tell parents they
      were prescribing off label, and 67% did not inform the family's general
      practitioner. Many respondents did not believe it was necessary to carry out
      clinical trials in children for new (46%) or generic (64%) medicines. However,
      52% of respondents stated that they would be willing to undertake clinical
      studies and recruit their own patients (61%) or children (73%) to take part in
      such studies. CONCLUSIONS: Among Scottish paediatricians there is concern about
      off label prescribing, although the majority do not consider it necessary to
      inform parents or GP colleagues. The need for clinical trials in children was
      recognised but there was a less than wholehearted acceptance of the need for such
      studies, at variance with the current drive to promote clinical trials in this
      age group.

PMID- 16443616
TI  - Prognostic predictive values of serum cytochrome c, cytokines, and other
      laboratory measurements in acute encephalopathy with multiple organ failure.
AB  - AIMS: To evaluate the prognostic predictive values of cytochrome c, cytokines,
      and other laboratory measurements in serum collected during neurological onset in
      acute encephalopathy with multiple organ failure. METHODS: In addition to general
      laboratory examinations, the concentrations of cytochrome c (apoptosis marker)
      and cytokines (inflammatory markers) were measured in serum samples collected at
      the initial phase in 29 patients with acute encephalopathy. The obtained values
      were evaluated as predictors for the development of severe encephalopathy.
      RESULTS: Cytochrome c, tumour necrosis factor alpha (TNF-alpha), interleukin 6
      (IL-6), soluble TNF-receptor 1 (sTNF-R1), and aspartate aminotransferase (AST)
      concentrations at the initial phase were high and correlated well with patient
      outcome. High concentrations of serum cytochrome c (>45 ng/ml), sTNF-R1 (>2000
      pg/ml), AST (>58 IU/dl), IL-6 (>60 pg/ml), and TNF-alpha (>15 pg/ml) predicted an
      unfavourable prognosis (sequelae and death) at 93%, 79%, 82%, 77%, and 60%,
      respectively. The specificity of those markers was 100%, 89%, 83%, 100%, and
      100%, respectively. CONCLUSIONS: Serum cytochrome c is the most sensitive and
      specific predictor for the development of severe encephalopathy at the initial
      phase. Results suggest that this marker might be used to guide decisions
      regarding the start of the initial treatment and further intensive care.

PMID- 16443617
TI  - Laser surface modification of Ti--6Al--4V: wear and corrosion characterization in
      simulated biofluid.
AB  - Laser surface melting (LSM) of Ti-6Al-4V is performed in argon to improve its
      properties, such as microstructure, corrosion, and wear for biomedical
      applications. Corrosion behavior is investigated by conducting electrochemical
      polarization experiments in simulated body fluid (Ringer's solution) at 37 C.
      Wear properties are evaluated in Ringer's solution using pin-on-disc apparatus at
      a slow speed. Untreated Ti-6Al-4V contains alpha+beta phase. After laser surface
      melting, it transforms to acicular alpha embedded in the prior beta matrix. Grain
      growth in the range of 65-89 microm with increase in laser power from 800 to 1500
      W due to increase in associated temperature is observed. The hardness of as
      laserprocessed Ti-6Al-4V alloy is more (275-297 HV) than that of the untreated
      alloy (254 HV). Passivation currents are significantly reduced to < 4.3
      microA/cm2 after laser treatment compared to untreated Ti-6Al-4V (approximately
      12 microA/cm2). The wear resistance of laser-treated Ti-6Al-4V in simulated body
      fluid is enhanced compared to that of the untreated one. It is the highest for
      the one that is processed at a laser power of 800 W. Typical micro-cutting
      features of abrasive wear is the prominent mechanism of wear in both untreated
      and as-laser-treated Ti-6Al-4V. Fragmentation of wear debris assisted by
      microcracking was responsible for mass loss during the wear of untreated Ti-6Al
      4V in Ringer's solution.

PMID- 16443619
TI  - Influence of a pre-blended antibiotic (gentamicin sulfate powder) on various
      mechanical, thermal, and physical properties of three acrylic bone cements.
AB  - The aim of this work was to determine an array of mechanical, physical, and
      thermal properties of three pairs of commercially available acrylic bone cement
      brands, with the brands in each pair having the same compositions except that one
      contains 4.22 wt/wt% gentamicin sulfate blended with the powder by the
      manufacturer and the other one does not. The difference between the pairs was in
      the viscosity of the curing cement dough, with one pair of 'low-viscosity', one
      pair of 'medium-viscosity', and one pair of 'high-viscosity' brands being used.
      Thus, the brands studied cover the range of those used in anchoring some total
      joint replacements (TJRs). The properties determined were the strength, modulus,
      and work-to-fracture (all under four-point bending), plane-strain fracture
      toughness, Weibull mean fatigue life (fatigue conditions: 15 MPa; 2 Hz),
      activation energy and frequency factor for the cement polymerization process
      (both determined, using differential scanning calorimetry, at heating rates of 5,
      10, 15, and 20 K min (1)), and the diffusion coefficient for the absorption of
      phosphate-buffered saline at 37 C by the cured cement. For each property
      determined, there was no significant difference in the mean values for the brands
      in each of the pairs. These results indicate that over the range of cement brands
      that are widely used in the anchoring of cemented TJRs, the addition of
      gentamicin sulfate powder does not degrade the properties of the cement, and,
      hence, may not adversely affect the in vivo longevity of the replacement.

PMID- 16443618
TI  - Fibronectin immobilization using water-soluble carbodiimide on poly-L-lactic acid
      for enhancing initial fibroblast attachment.
AB  - The aim of this study is to evaluate the influence of fibronectin immobilization
      on poly-L-lactic acid (PLA) films on the initial attachment of human gingival
      fibroblasts. Carboxylic acid groups are chemically introduced on the PLA films'
      surface by surface hydrolysis with 0.5 M NaOH. The contact angle of PLA surface
      with respect to double-distilled water decreases significantly after NaOH
      hydrolysis. X-ray photoelectron spectroscopy (XPS) also reveals significantly
      higher intensities of C(C=O)/C(C-O) after NaOH hydrolysis. Fibronectin is
      immobilized onto the hydrolyzed PLA surface through a condensation reaction
      between the carboxylic acid groups on the hydrolyzed PLA surface and the amino
      groups of fibronectin using water-soluble carbodiimide. XPS analysis shows that
      the fibronectin-immobilized PLA surface is enriched with nitrogen atoms. The
      immobilization of fibronectin significantly enhances the number of initially
      attached human gingival fibroblasts on the PLA surface. No obvious differences in
      morphology are noted between fibroblasts cultured on native PLA and on
      fibronectin-immobilized PLA. Fibronectin can be immobilized onto the PLA surface
      after NaOH hydrolysis and this is effective in enhancing the initial attachment
      of human gingival fibroblasts.

PMID- 16443620
TI  - Fabrication and characterization of polysulfone-dicalcium silicate composite
      films.
AB  - Polysulfone (PSU) composite films filled with Beta-dicalcium silicate (Beta
      Ca(2)SiO(4)) particles are prepared by the solvent casting-evaporation method.
      The surface morphologies and mechanical properties of the films are determined.
      The bioactivity of the composite films is evaluated by soaking them in simulated
      body fluid (SBF) and the results show that the composites are bioactive as they
      induce the formation of hydroxyapatite (HAp) on the surface of the composite
      films. The measurement of the water contact angles suggests that the
      incorporation of Beta-Ca(2)SiO(4) particles into PSU matrix can improve the
      hydrophilicity of the composite. PSU composite films filled with modified Beta
      dicalcium silicate (Beta-mCa(2)SiO(4)) particles are also prepared after Beta
      Ca(2)SiO(4) particles are treated with dodecyl alcohol through surface
      esterification reactions. The infrared spectra of the Beta-mCa(2)SiO(4) particles
      before and after aging in water indicate that the surface modification is
      reversible. The scanning electron microscope (SEM) images (micrographs) of both
      composites show that the dispersion of inorganic particles in the polymer matrix
      improves after surface modification. The PSU-Beta-mCa(2)SiO(4) composite is still
      bioactive and exhibits the same water contact angle after aging in water as
      compared to that of the PSU-Beta-Ca(2)SiO(4) composite. All these results suggest
      that the incorporation of Beta-Ca(2)SiO(4) particles is a useful method to
      prepare composites with improved bioactivity and hydrophilicity, and the surface
      modification of Beta-Ca(2)SiO(4) particles can improve the dispersion while
      retaining the bioactivity and hydrophilicity.

PMID- 16443622
TI  - Bone augmentation with bioactive glass in three cases of dental implant
      placement.
AB  - This study reports the clinical use of a bioactive bone graft material,
      PerioGlas, in the treatment of dental extraction sites before dental implant
      placement, to effect bone regeneration and to give early fixation to the
      implant.PerioGlas, granules, ranging from 90 to 710 mm, are implanted after tooth
      extraction in three patients; after 6 months bone biopsies were performed in the
      site of the glass implantation and observed under Electron Scanning Microscopy.
      All the granules showed a biodegradation involving precipitation of calcium
      phosphate that worked as a scaffold for osteoblasts colonization. All cases
      examined showed the bioactivity of PerioGlas granules resulting in new bone
      formation and biodegradation of the glass. After a two-year clinical follow-up
      all the implants were successfully loaded and appeared stable.

PMID- 16443621
TI  - Characterization and in vitro bioactivity of zinc-containing bioactive glass and
      glass-ceramics.
AB  - Zinc-containing glass is prepared by the substitution of CaO in 58S bioactive
      glass with 0.5 and 4 wt% ZnO, and glass-ceramics are obtained by heat-treating
      the glass at 1,200 C. The bending strength and in vitro bioactivity of the glass
      and glass-ceramics are evaluated. The results indicate that Zn promotes the
      crystallization of SiO(2) and wollastonite in glass-ceramics, and proper
      crystallization can enhance the bending strength of the glass-ceramic. The in
      vitro results show that ZnO in glass retards the hydroxyapatite (HA) nucleation
      at the initial stage of simulated body fluid (SBF) soaking, but does not affect
      the growth of HA after long periods of soaking, and the ionic products of 58S4Z
      glass can stimulate the proliferation of osteoblast at certain concentrations.
      Osteoblasts attach well on both glass samples and glass-ceramic samples, but the
      high Si ion concentration released from glass samples restrains the proliferation
      of osteoblasts after 3 days of culture. In contrast, osteoblasts show good
      proliferation on glass-ceramic samples, and ZnO in glass-ceramics promotes the
      proliferation rate. The results in this study suggest that the glass and glass
      ceramics with different ZnO content might be used as bioactive bone implant
      materials in different applications.

PMID- 16443623
TI  - Biocompatibility of Beta-tricalcium phosphate root replicas in porcine tooth
      extraction sockets - a correlative histological, ultrastructural, and x-ray
      microanalytical pilot study.
AB  - This investigation studies porcine tissue response in tooth extraction sockets
      treated with root replicas made out of Beta-tricalcium phosphate (Beta-TCP; Beta
      Ca(3)(PO(4))(2)) granules, molded and held together by thermal fusion of a thin
      film of polyglycolic-polylactic acid copolymer. Six left mandibular third
      incisors (n (1)/4 6) of experimental pigs are treated with the root replicas and
      four contralateral incisors are used as nontreated controls (n (1)/4 4). Two
      animals each were killed at 20, 40, and 60 weeks of observation periods. The
      mandibular jaw segments were prepared in toto for light microscopy by resin
      embedding and serial ground sectioning. Additionally, one Beta-TCP-treated socket
      at 60 weeks was thoroughly investigated by correlative light, electron
      microscopic and electron probe X-ray microanalysis to assess the bio
      absorbability and host removal of the replica material from the implant site. The
      extraction wounds of the animals healed satisfactorily with very little
      histologically observable differences in the healing pattern of the test and
      control sites. The Beta-TCP was completely removed from extracellular sites, but
      at 60 weeks, remnants of it were found in the cytoplasm of multinucleated giant
      cells. The root replicas made out of Beta-TCP were biocompatible and
      bioabsorbable. Osseous healing occurred both in the test and control sockets, but
      the healing process was delayed due to the presence of Beta-TCP particles.

PMID- 16443624
TI  - Insulin loaded eudragit L100 microspheres for oral delivery: preliminary in vitro
      studies.
AB  - Eudragit L100 microspheres were prepared using water-in-oil-in water (w/o/w)
      emulsion-solvent evaporation with polysorbate 20 as dispersing agent in the
      internal aqueous phase, and PVA/PVP as stabilizer in the external aqueous phase.
      Smaller internal and external aqueous phases provided higher drug encapsulation.
      The PVA-stabilized microspheres having maximum drug encapsulation (84.5 2.8%)
      released 7% insulin at pH 1.0 in 2 h. In phosphate buffer (pH 7.4), microspheres
      showed an initial burst release of 21% in 1 h with additional 35% release in the
      next 5 h. The smaller the volumes of internal and external aqueous phases, the
      lower the initial burst release. The release of drug from microspheres followed
      Higuchi kinetics. Scanning electron microscopy of PVA stabilized microspheres
      demonstrated spherical particles with smooth surface and laser diffractometry
      revealed a mean particle size (V(m)) of 59.11 30 m.

PMID- 16443625
TI  - Novel amino acid-constructed polyalkenoates for dental glass-ionomer
      restoratives.
AB  - Several methacrylate or acrylate derivatives of natural amino acids were
      synthesized and characterized. Based upon these derivatives, novel amino acid
      constructed polyalkenoic acids were prepared and used to formulate glass-ionomer
      cements (GICs) with Fuji II glass filler. The effects of type of derivatives,
      molar ratio, molecular weight, and powder/liquid ratio were investigated. The
      results show that amino acid-constructed polyalkenoic acids can be formed only
      from amino acid methacrylate derivatives or by copolymerization of methacrylate
      with acrylate derivatives. Strong hydrogen bond interactions failed the polymer
      formation from acrylate derivatives. The cement composed of poly(methacryloyl
      glutamic acid-co-acryloyl beta-alanine) with the molar ratio of 8:2 demonstrated
      the best mechanical strengths along with a workable viscosity. By using the
      powder/liquid ratio of 3.0/1, the experimental cement exhibited a significantly
      higher FS (27.7 MPa), and nearly the same CS (198.5 MPa) and DTS (11.8 MPa), as
      compared to Fuji II (18.9 for FS, 189.1 for CS, and 11.4 MPa for DTS). During
      aging, the cement showed a significant increase in strength over 24 h, followed
      by a slow increase over 6 months.

PMID- 16443626
TI  - Bioactivity and mechanical properties of cellulose/carbonate hydroxyapatite
      composites prepared in situ through mechanochemical reaction.
AB  - Organic-inorganic composites, prepared from bone-bonding bioactive ceramics and
      organic polymers, are useful for novel bone substitutes having mechanical
      properties analogous to natural bone. We synthesized composites from cellulose
      and carbonate hydroxyapatite (CHAp) in situ through mechanochemical reaction.
      They contained B-type CHAp analogous to bone apatite. They showed a bending
      strengths of 10-13 MPa and Young's modulus of 1.5-2.2 GPa. We predicted their
      microstructure by comparing the measured density with the theoretical one.
      Cellulose was assumed to be distributed in the pore of CHAp at low cellulose
      content, and in grain boundaries of CHAp at high cellulose content. The
      composites formed calcium phosphate on their surfaces in simulated body fluid,
      meaning that they have a potential to be bioactive.

PMID- 16443627
TI  - Determination of crystallinity and crystal structure of Hylamer polyethylene
      after in vivo wear.
AB  - Hylamer polyethylene is a crystalline form of polyethylene of 70% crystallinity
      whereas conventional polyethylene (PE) has 50% crystallinity. Crystallinity is
      the percentage by weight of the crystalline phase present in the whole polymer,
      which comprises both amorphous and crystalline phases. Clinical experience has
      shown that Hylamer components used in joint prostheses, if sterilized by gamma
      rays in the presence of oxygen, are easily affected by wear, which leads to
      osteolysis. The authors have analyzed the crystallinity of polyethylene liners
      removed from seven patients who had received Hylamer polyethylene implants
      sterilized by gamma rays in air and had suffered prosthetic loosening, using
      Raman spectroscopy coupled with partial least squares (PLS) analysis. The results
      have been compared to those of two controls who had received Hylamer polyethylene
      implants sterilized by gamma irradiation in a nitrogen atmosphere. The crystal
      structure of wear particles released into the tissues from the Hylamer liners
      sterilized by gamma rays in air is also studied. The materials undergoing two
      different types of sterilization methods show different crystallinity values
      (71.50 vs. 69.43), but the crystallinity do not change according to wear (worn
      and unworn liner region). Both monoclinic and orthorhombic phases are present in
      the liner, while in wear debris prevalently monoclinic crystals are found in both
      types of sterilized liners. Different crystallinity rates can explain different
      wear rates observed in vivo.

PMID- 16443628
TI  - A novel akermanite bioceramic: preparation and characteristics.
AB  - Akermanite (Ca(2)MgSi(2)O(7)) ceramics are prepared by sintering akermanite
      powder compacts at 1370 C for 6 h. The sintering behavior and mechanical
      properties of akermanite ceramics are investigated. The bioactivity of akermanite
      ceramics is evaluated by soaking in simulated body fluid (SBF), and
      hydroxyapatite (HAp) formation on the surface of akermanite ceramics after
      soaking is characterized by X-ray diffraction (XRD), energy dispersive
      spectrometry (EDS), and scanning electron microscopy (SEM). The results show that
      the bending strength of akermanite ceramics can reach 176 MPa, the fracture
      toughness is 1.83 MPa m(1/2), and akermanite ceramics can induce HAp formation on
      their surface when soaked in SBF. Our results indicate that akermanite ceramics
      are bioactive, and possess improved mechanical properties compared with those of
      HAp ceramics and may be used as bioactive implant materials.

PMID- 16443629
TI  - Biocompatibility of poly-DL-lactic acid (PDLLA) for lung tissue engineering.
AB  - This study explores the possibility of growing lung cells on poly-DL-lactic acid
      (PDLLA) scaffolds, with a view to in future engineer pulmonary tissue for human
      implantation. As a first step in this process, the ability of PDLLA to maintain
      the growth of lung epithelium is tested using a robust cell line. Poly-DL-lactic
      acid has been investigated in two forms, as planar discs and as 3-D foams, and it
      has been demonstrated that PDLLA is not only nontoxic to pneumocytes but it also
      actively supports their growth. The initial findings suggest that the material is
      an appropriate matrix for engineering of distal lung tissue.

PMID- 16443630
TI  - Properties of tableted high-amylose corn starch-pectin blend microparticles
      intended for controlled delivery of diclofenac sodium.
AB  - This study reports the properties of tableted microparticles based on high
      amylose corn starch (HACS)-pectin blend polymers as the controlled release system
      for diclofenac sodium (DS). HACS-pectin blend microparticles are prepared through
      a modified process by the spray drying technique, which is a widely used
      microencapsulation technique in the pharmaceutical industry. The mean particle
      size of various formulations of blend microparticles is in the range of 5.8-7.3
      mum. Fourier transform infrared (FTIR) spectroscopy study reveals the absence of
      well-defined interaction between HACS-pectin and polymers-DS. The blend
      microparticles thus prepared were compressed into tablets using the directly
      compressible excipients. A cross-sectional view of the tablet reveals the
      presence of nearly spherical shaped particles in the tablet, suggesting that the
      system chosen is ideal for tableting. In vitro drug release study indicates that
      tableted microparticulate system is found to be suitable for the manipulation of
      release behavior for DS in the gastrointestinal tract. Release mechanism of the
      DS from tableted microparticles is by Fickian diffusion since the value of n
      approaches 0.5.

PMID- 16443631
TI  - Effect of surface treatments on anodic oxide film growth and electrochemical
      properties of tantalum used for biomedical applications.
AB  - Self-expandable nitinol (nickel-titanium) alloys and 316L stainless steel are the
      most commonly used materials in the production of coronary stents. However,
      tantalum (Ta) has already been used to make stents for endovascular surgery and
      may constitute an alternative to other materials because of its better
      electrochemical performance, namely its higher corrosion resistance, as well as
      its radio-opacity. The characterization of wet polished, chemically polished, wet
      polished anodized, and chemically polished anodized Ta electrodes has been
      performed in a 0.15 M NaCl solution (simulated body fluid) using Ucorr = f(t)
      measurements, anodic polarizations, capacity measurements, anodic oxidations, and
      atomic force microscopy (AFM) imaging. Anodic polarization curves have shown that
      the abnormal current density peak with a maximum value around 1.65 V (critical
      applied potential, Uc) disappeared for the anodized electrodes indicating a
      probable relationship between the surface states and the film growth. These
      results are confirmed by capacity measurements. The behavior of wet polished and
      chemically polished electrodes during anodic oxidations seemingly indicated that
      for these particular treatments the film growth is different. The AFM images and
      roughness measurements have shown that chemical polishing produced smoother
      electrodes, a fact probably related to the differences in film growth.

PMID- 16443632
TI  - Polyvinyl alcohol--gelatin patches of salicylic acid: preparation,
      characterization and drug release studies.
AB  - Polyvinyl alcohol-gelatin patches were developed and salicylic acid was
      incorporated at different stages of preparation of the patches. The patches were
      characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray
      diffraction (XRD), differential scanning calorimetry, tensile strength test, and
      scanning electron microscopy. The release patterns of the drug from the patches
      were also studied. The FTIR spectra of the blank patch indicated complete
      esterification of the free carboxylic groups of gelatin. The XRD studies
      indicated a crystalline form of the drug entrapped in the patches. Release of the
      drug from the patches followed Higuchian/Fickian kinetics indicating a diffusion
      controlled release process.

PMID- 16443633
TI  - Enhancing instance-based classification with local density: a new algorithm for
      classifying unbalanced biomedical data.
AB  - MOTIVATION: Classification is an important data mining task in biomedicine. In
      particular, classification on biomedical data often claims the separation of
      pathological and healthy samples with highest discriminatory performance for
      diagnostic issues. Even more important than the overall accuracy is the balance
      of a classifier, particularly if datasets of unbalanced class size are examined.
      RESULTS: We present a novel instance-based classification technique which takes
      both information of different local density of data objects and local cluster
      structures into account. Our method, which adopts the basic ideas of density
      based outlier detection, determines the local point density in the neighborhood
      of an object to be classified and of all clusters in the corresponding region. A
      data object is assigned to that class where it fits best into the local cluster
      structure. The experimental evaluation on biomedical data demonstrates that our
      approach outperforms most popular classification methods. AVAILABILITY: The
      algorithm LCF is available for testing under
      http://biomed.umit.at/upload/lcfx.zip.

PMID- 16443634
TI  - A novel domain suggests a ciliary function for ASPM, a brain size determining
      gene.
AB  - The N-terminal domain of abnormal spindle-like microcephaly-associated protein
      (ASPM) is identified as a member of a novel family of ASH (ASPM, SPD-2, Hydin)
      domains. These domains are present in proteins associated with cilia, flagella,
      the centrosome and the Golgi complex, and in Hydin and OCRL whose deficiencies
      are associated with hydrocephalus and Lowe oculocerebrorenal syndrome,
      respectively. Genes encoding ASH domains thus represent good candidates for
      primary ciliary dyskinesias. ASPM has been proposed to function in neurogenesis
      and to be a major determinant of cerebral cortical size in humans. Support for
      this hypothesis stems from associations between mutations in ASPM and primary
      microcephaly, and from the rapid evolution of ASPM during recent hominid
      evolution. The identification of the ASH domain family instead indicates possible
      roles for ASPM in sperm flagellar or in ependymal cells' cilia. ASPM's rapid
      evolution may thus reflect selective pressures on ciliary function, rather than
      pressures on mitosis during neurogenesis.

PMID- 16443635
TI  - Genomic island identification in Vibrio vulnificus reveals significant genome
      plasticity in this human pathogen.
AB  - Genomic islands (GIs) are large chromosomal regions present in a subset of
      bacterial strains that increase the fitness of the organism under specific
      conditions. We compared the complete genome sequences of two Vibrio vulnificus
      strains YJ016 and CMCP6 and identified 14 regions (ranging in size from 14 to 117
      kb), which had the characteristics of GIs. Bioinformatic analysis of these 14 GI
      regions identified the presence of phage-like integrase genes, aberrant GC
      content and genome signature (dinucleotide frequency) within each GI compared
      with the core genome indicating that these regions were acquired from an
      anomalous source. We examined the distribution of the nine GIs from strain YJ016
      among 27 V. vulnificus isolates and found that most GIs were absent from the
      majority of these isolates. The chromosomal insertion sites of three GIs were
      adjacent to tRNA sites, which contained novel horizontally acquired DNA in all
      six available sequenced Vibrionaceae genomes. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 16443636
TI  - Synthetic biology: challenges ahead.

PMID- 16443637
TI  - HaptenDB: a comprehensive database of haptens, carrier proteins and anti-hapten
      antibodies.
AB  - The key requirement for successful immunochemical assay is the availability of
      antibodies with high specificity and desired affinity. Small molecules, when used
      as haptens, are not immunogenic. However, on conjugating with carrier molecule
      they elicit antibody response. The production of anti-hapten antibodies of
      desired specificity largely depends on the hapten design (preserving greatly the
      chemical structure and spatial conformation of target compound), selection of the
      appropriate carrier protein and the conjugation method. This manuscript describes
      a curated database HaptenDB, where information is collected from published
      literature and web resources. The current version of the database has 2021
      entries for 1087 haptens and 25 carrier proteins, where each entry provides
      comprehensive details about (1) nature of the hapten, (2) 2D and 3D structures of
      haptens, (3) carrier proteins, (4) coupling method, (5) method of anti-hapten
      antibody production, (6) assay method (used for characterization) and (7)
      specificities of antibodies. The current version of HaptenDB covers a wide array
      of haptens including pesticides, herbicides, insecticides, drugs, vitamins,
      steroids, hormones, toxins, dyes, explosives, etc. It provides internal and
      external links to various databases/resources to obtain further information about
      the nature of haptens, carriers and respective antibodies. For structure
      similarity comparison of haptens, the database also integrates tools like JME
      Editor and JMOL for sketching, displaying and manipulating hapten 2D/3D
      structures online. So the database would be of great help in identifying
      functional group(s) in smaller molecules using antibodies as well as for the
      development of immunodiagnostics/therapeutics by providing data and procedures
      available so far for the generation of specific or cross-reactive antibodies.
      AVAILABILITY: HaptenDB is available on http://www.imtech.res.in/raghava/haptendb/
      and http://bioinformatics.uams.edu/raghava/haptendb/ (Mirror site).

PMID- 16443639
TI  - Short-term mortality in hip fracture patients admitted during weekends and
      holidays.
AB  - BACKGROUND: Acute surgical admission during weekends, with reduced staffing
      levels, has been associated with increased risk of mortality, but the effect of
      longer vacation/holiday periods has not been studied. We therefore examined early
      postoperative mortality in hip fracture patients admitted during weekends and
      holiday periods, compared with normal weekdays. METHODS: Prospective, descriptive
      study in 600 consecutive hip fracture patients treated with a well-defined
      multimodal care plan, in a specialized hip fracture unit between September 2002
      and July 2004. Patients were stratified according to admission on a weekday or
      during weekends/holiday periods. RESULTS: were analysed with univariate and
      multivariate analyses. Results. Three hundred and thirty-two patients were
      admitted during weekdays, 118 during weekends and 150 during holiday periods.
      Both 5- and 30-day postoperative mortality were significantly higher in patients
      admitted during holiday periods than during weekends and weekdays, 8.0% vs 2.5%
      and 1.8%, respectively (P=0.01) and 19.3% vs 12.7% and 11.1%, respectively
      (P=0.05). In a multivariate analysis, admission during holiday periods was still
      a significant independent risk factor for both 5-day (4.34, 95% CI 1.74-10.8) and
      30-day mortality (1.84, 95% CI 1.08-3.12). CONCLUSION: Staff reduction during
      holiday periods in units that care for acute surgical patients may adversely
      influence postoperative outcome. This may have important consequences both for
      outcome analysis of interventions and the planning of resource management in
      surgical units.

PMID- 16443638
TI  - The Narcotrend 'depth of anaesthesia' monitor cannot reliably detect
      consciousness during general anaesthesia: an investigation using the isolated
      forearm technique.
AB  - BACKGROUND: During general anaesthesia in the presence of neuromuscular blocking
      drugs clinical criteria cannot detect the presence of consciousness. Various
      'depth of anaesthesia' monitors are available which claim to prevent
      consciousness and/or reduce anaesthetic drug use. This study uses the Narcotrend
      anaesthesia brain monitor to guide anaesthetic administration but at the same
      time checks for the presence of intra-operative consciousness by using the
      'isolated forearm' technique throughout the whole surgical/anaesthetic procedure.
      METHODS: Twelve women presenting for major gynaecological surgery under general
      anaesthesia, which included the use of neuromuscular blocking drugs, had a target
      controlled infusion of propofol adjusted according to the anaesthetic 'stage'
      indicated by a Narcotrend 'Depth of Anaesthesia Monitor'. Throughout surgery the
      isolated forearm technique was used to detect for the presence of consciousness
      at 1 min intervals. RESULTS: Isolated forearm responses to commands occurred in
      all 12 patients at some time during surgery, frequently in the absence of any
      significant changes in the usually monitored clinical variables. Overall, the 12
      patients responded a total of 92 times during surgery. Only 41 (45%) responses
      were associated with an increase in the Narcotrend stage to a level suggesting
      consciousness (above stage C(0)). For the remaining responses, either there was
      no significant increase in the Narcotrend stage (above C(0)) or there was no
      change at all in the Narcotrend stage before, during, or after the patient
      responded to the taped command. CONCLUSIONS: The Narcotrend was unable to
      differentiate reliably between conscious and unconscious patients during general
      anaesthesia when neuromuscular blocking agents were used.

PMID- 16443640
TI  - Treatment with phosphodiesterase inhibitors type III and V: milrinone and
      sildenafil is an effective combination during thromboxane-induced acute pulmonary
      hypertension.
AB  - OBJECTIVES: To evaluate the effects of phosphodiesterase type III and V (PDEIII
      and PDEV) inhibition on pulmonary and systemic haemodynamics in a porcine model
      of acute pulmonary hypertension. METHODS: Twenty-four adult swine were
      anaesthetized with 1 MAC isoflurane and mechanically ventilated with an FI(O(2))
      of 100%. Micromanometer-tipped catheters were placed in the ascending aorta,
      pulmonary artery and right ventricle. Pulmonary flow was measured with a
      perivascular probe using transit time ultrasound. Pulmonary hypertension was
      induced with a continuous infusion of the thromboxane analogue, U46619. The
      animals were then randomized to four groups: Group 1 (n=6) received 50 mg of
      sildenafil (PDEV inhibitor) diluted in water via an orogastric tube; Group 2
      (n=6) received 50 microg kg(-1) of i.v. milrinone (PDEIII inhibitor); Group 3
      (n=6) received sildenafil followed by milrinone; and Group 4 (n=6) received
      placebo via an orogastric tube. RESULTS: Pulmonary hypertension was achieved in
      all animals. Calculated pulmonary vascular resistance decreased by an average of
      36% after sildenafil (P<0.05), 41% after milrinone (P<0.05), and 61% with both
      drugs combined (P<0.05). Systemic vascular resistance decreased by 37% (P<0.05)
      with milrinone alone, and 36% (P<0.05) with milrinone and sildenafil combined but
      it was preserved in the sildenafil group. Cardiac output and right ventricular
      dP/dT were significantly improved after milrinone or both drugs combined, but not
      with sildenafil. CONCLUSION: Milrinone and sildenafil are effective pulmonary
      vasodilators, with independent action and additive effect. Both drugs combined
      achieved a better haemodynamic profile, with greater pulmonary vasodilatation and
      increased contractility but without additional systemic vasodilatation. The
      systemic haemodynamic profile (systemic vasodilation, cardiac output, right
      ventricular dP/dT) is improved with milrinone but not with sildenafil.

PMID- 16443641
TI  - Characterization of acid signaling in rat vagal pulmonary sensory neurons.
AB  - Local tissue acidosis frequently occurs in airway inflammatory and ischemic
      conditions. The effect of physiological/pathophysiological-relevant low pH (7.0
      5.5) on isolated rat vagal pulmonary sensory neurons was investigated using whole
      cell perforated patch-clamp recordings. In voltage-clamp recordings, vagal
      pulmonary sensory neurons exhibited distinct pH sensitivities and different
      phenotypes of inward current in responding to acidic challenge. The current
      evoked by lowering the pH of extracellular solution to 7.0 consisted of only a
      transient, rapidly inactivating component with small amplitude. The amplitude of
      this transient current increased when the proton concentration was elevated. In
      addition, a slow, sustained inward current began to emerge when pH was reduced to
      <6.5. The current-voltage curve indicated that the transient component of acid
      evoked current was carried predominantly by Na+. This transient component was
      dose-dependently inhibited by amiloride, a common blocker of acid-sensing ion
      channels (ASICs), whereas the sustained component was significantly attenuated by
      capsazepine, a selective antagonist of transient receptor potential vanilloid
      receptor subtype-1 (TRPV1). The two components of acid-evoked current also
      displayed distinct recovery kinetics from desensitization. Furthermore, in
      current-clamp recordings, transient extracellular acidification depolarized the
      membrane potential and generated action potentials in these isolated neurons. In
      summary, our results have demonstrated that low pH can stimulate rat vagal
      pulmonary sensory neurons through the activation of both ASICs and TRPV1. The
      relative roles of these two current species depend on the range of pH and vary
      between neurons.

PMID- 16443642
TI  - Inhaled NO restores lung structure in eNOS-deficient mice recovering from
      neonatal hypoxia.
AB  - We have previously shown that neonatal mice deficient in endothelial nitric oxide
      synthase (eNOS-/-) are more susceptible to hypoxic inhibition of alveolar and
      vascular growth. Although eNOS is downregulated, the role of nitric oxide (NO)
      during recovery after neonatal lung injury is poorly understood. We hypothesized
      that lung vascular and alveolar growth would remain impaired in eNOS-/- mice
      during recovery in room air and that NO therapy would augment compensatory lung
      growth in the eNOS-/- mice during recovery. Mice (1 day old) from heterozygous
      (eNOS+/-) parents were placed in hypobaric hypoxia (Fi(O2) = 0.16). After 10
      days, pups were to recovered in room air (HR group) or inhaled NO (10
      parts/million; HiNO group) until 3 wk of age, when lung tissue was collected.
      Morphometric analysis revealed that the eNOS-/- mice in the HR group had
      persistently abnormal lung structure compared with eNOS-sufficient (eNOS+/+) mice
      (increased mean linear intercept and reduced radial alveolar counts, nodal point
      density, and vessel density). Lung morphology of the eNOS+/- was not different
      from eNOS+/+. Inhaled NO after neonatal hypoxia stimulated compensatory lung
      growth in eNOS-/- mice that completely restored normal lung structure. eNOS+/-
      mice (HR group) had a 2.5-fold increase in lung vascular endothelial growth
      factor (VEGFR)-2 protein compared with eNOS+/+ (P < 0.05). eNOS-/- mice (HiNO
      group) had a 66% increase in lung VEGFR-2 protein compared with eNOS-/- (HR
      group; P < 0.01). We conclude that deficiency of eNOS leads to a persistent
      failure of lung growth during recovery from neonatal hypoxia and that, after
      hypoxia, inhaled NO stimulates alveolar and vascular growth in eNOS-/- mice.

PMID- 16443643
TI  - Peroxisome proliferator-activated receptor-gamma inhibits cigarette smoke
      solution-induced mucin production in human airway epithelial (NCI-H292) cells.
AB  - The main etiologic factor for chronic bronchitis is cigarette smoke. Exposure to
      cigarette smoke is reported to induce goblet cell hyperplasia and mucus
      production. Mucin synthesis in airways has been reported to be regulated by the
      EGFR system. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a
      member of the ligand-activated nuclear receptor superfamily. PPAR-gamma is
      implicated in anti-inflammatory responses, but mechanisms underlying these varied
      roles remain ill-defined. Recently, reports have shown that upregulation of
      phosphatase and tensin homolog deleted on chromosome 10 (PTEN) might be one of
      the mechanisms through which PPAR-gamma agonists exert their anti-inflammatory
      actions. However, no data are available on the role of PPAR-gamma in smoke
      induced mucin production. In this study, we investigated the effect of PPAR-gamma
      agonist (rosiglitazone) on smoke-induced mucin production in NCI-H292 cells.
      Exposure to cigarette smoke causes a significant decrease in PTEN expression and
      increases dose-dependent EGFR-specific tyrosine phosphorylation, resulting in
      MUC5AC mucin production in NCI-H292 cells. PPAR-gamma agonists or specific
      inhibitors of phosphoinositide 3-kinase exert inhibition of cigarette smoke
      induced mucin production, with the upregulation of PTEN signaling and
      downregulation of Akt expression. This study demonstrates that PPAR-gamma agonist
      functions as a regulator of epithelial cell inflammation that may result in
      reduction of mucin-producing cells in airway epithelium.

PMID- 16443644
TI  - Differential induction of apoptosis by cigarette smoke extract in primary human
      lung fibroblast strains: implications for emphysema.
AB  - Cigarette smoke is the principal cause of emphysema. Recent attention has focused
      on the loss of alveolar fibroblasts in the development of emphysema. Fibroblasts
      may become damaged by oxidative stress and undergo apoptosis as a result of
      cigarette smoke exposure. Not all smokers develop lung diseases associated with
      tobacco smoke, a fact that may reflect individual variation among human
      fibroblast strains. We hypothesize that fibroblasts from different human beings
      vary in their ability to undergo apoptosis after cigarette smoke exposure. This
      could account for emphysematous changes that occur in the lungs of some but not
      all smokers. Primary human lung fibroblast strains were exposed to cigarette
      smoke extract (CSE) and assessed for viability, morphological changes, and
      mitochondrial transmembrane potential as indicators of apoptosis. We also
      examined the generation of intracellular reactive oxygen species (ROS), 4-hydroxy
      2-nonenal, and changes in glutathione (GSH) and glutathione disulfide (GSSG)
      levels. Each human lung fibroblast strain exhibited a differential sensitivity to
      CSE as judged by changes in mitochondrial membrane potential, viability, ROS
      generation, and glutathione production. Interestingly, the thiol antioxidants N
      acetyl-L-cysteine and GSH eliminated CSE-induced changes in fibroblast morphology
      such as membrane blebbing, nuclear condensation, and cell size and prevented
      alterations in mitochondrial membrane potential and the generation of ROS. These
      findings support the concept that oxidative stress and apoptosis are responsible
      for fibroblast death associated with exposure to tobacco smoke. Variations in the
      sensitivity of fibroblasts to cigarette smoke may account for the fact that only
      some smokers develop emphysema.

PMID- 16443645
TI  - Attenuation of the pulmonary inflammatory response following butylated
      hydroxytoluene treatment of cytosolic phospholipase A2 null mice.
AB  - Administration of butylated hydroxytoluene (BHT) to mice causes lung damage
      characterized by the death of alveolar type I pneumocytes and the proliferation
      and subsequent differentiation of type II cells to replace them. Herein, we
      demonstrate this injury elicits an inflammatory response marked by chemokine
      secretion, alveolar macrophage recruitment, and elevated expression of enzymes in
      the eicosanoid pathway. Cytosolic phospholipase A(2) (cPLA(2)) catalyzes release
      of arachidonic acid from membrane phospholipids to initiate the synthesis of
      prostaglandins and other inflammatory mediators. A role for cPLA(2) in this
      response was examined by determining cPLA(2) expression and enzymatic activity in
      distal respiratory epithelia and macrophages and by assessing the consequences of
      cPLA(2) genetic ablation. BHT-induced lung inflammation, particularly monocyte
      infiltration, was depressed in cPLA(2) null mice. Monocyte chemotactic protein-1
      (MCP-1) content in bronchoalveolar lavage fluid increases after BHT treatment but
      before monocyte influx, suggesting a causative role. Bronchiolar Clara cells
      isolated from cPLA(2) null mice secrete less MCP-1 than Clara cells from wild
      type mice, consistent with the hypothesis that cPLA(2) is required to secrete
      sufficient MCP-1 to induce an inflammatory monocytic response.

PMID- 16443646
TI  - Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway
      primary cultures by small molecules.
AB  - Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in cftr, a
      gene encoding a PKA-regulated Cl(-) channel. The most common mutation results in
      a deletion of phenylalanine at position 508 (DeltaF508-CFTR) that impairs protein
      folding, trafficking, and channel gating in epithelial cells. In the airway,
      these defects alter salt and fluid transport, leading to chronic infection,
      inflammation, and loss of lung function. There are no drugs that specifically
      target mutant CFTR, and optimal treatment of CF may require repair of both the
      folding and gating defects. Here, we describe two classes of novel, potent small
      molecules identified from screening compound libraries that restore the function
      of DeltaF508-CFTR in both recombinant cells and cultures of human bronchial
      epithelia isolated from CF patients. The first class partially corrects the
      trafficking defect by facilitating exit from the endoplasmic reticulum and
      restores DeltaF508-CFTR-mediated Cl(-) transport to more than 10% of that
      observed in non-CF human bronchial epithelial cultures, a level expected to
      result in a clinical benefit in CF patients. The second class of compounds
      potentiates cAMP-mediated gating of DeltaF508-CFTR and achieves single-channel
      activity similar to wild-type CFTR. The CFTR-activating effects of the two
      mechanisms are additive and support the rationale of a drug discovery strategy
      based on rescue of the basic genetic defect responsible for CF.

PMID- 16443647
TI  - ATP hydrolysis stimulates large length fluctuations in single actin filaments.
AB  - Polymerization dynamics of single actin filaments is investigated theoretically
      using a stochastic model that takes into account the hydrolysis of ATP-actin
      subunits, the geometry of actin filament tips, and the lateral interactions
      between the monomers as well as the processes at both ends of the polymer. Exact
      analytical expressions are obtained for the mean growth velocity, for the
      dispersion in the length fluctuations, and the nucleotide composition of the
      actin filaments. It is found that the ATP hydrolysis has a strong effect on
      dynamic properties of single actin filaments. At high concentrations of free
      actin monomers, the mean size of the unhydrolyzed ATP-cap is very large, and the
      dynamics is governed by association/dissociation of ATP-actin subunits. However,
      at low concentrations the size of the cap becomes finite, and the dissociation of
      ADP-actin subunits makes a significant contribution to overall dynamics. Actin
      filament length fluctuations reach a sharp maximum at the boundary between two
      dynamic regimes, and this boundary is always larger than the critical
      concentration for the actin filament's growth at the barbed end, assuming the
      sequential release of phosphate. Random and sequential mechanisms of hydrolysis
      are compared, and it is found that they predict qualitatively similar dynamic
      properties at low and high concentrations of free actin monomers with some
      deviations near the critical concentration. The possibility of attachment and
      detachment of oligomers in actin filament's growth is also discussed. Our
      theoretical approach is successfully applied to analyze the latest experiments on
      the growth and length fluctuations of individual actin filaments.

PMID- 16443648
TI  - Molecular dynamics of surfactant protein C: from single molecule to heptameric
      aggregates.
AB  - Surfactant protein C (SP-C) is a membrane-associated protein essential for normal
      respiration. It has been found that the alpha-helix form of SP-C can undergo,
      under certain conditions, a transformation from an alpha-helix to a beta-strand
      conformation that closely resembles amyloid fibrils, which are possible
      contributors to the pathogenesis of pulmonary alveolar proteinosis. Molecular
      dynamics simulations using the NAMD2 package were performed for systems
      containing from one to seven SP-C molecules to study their behavior in water. The
      results of our simulations show that unfolding of the protein occurs at the amino
      terminal, and despite this unfolding, no transition from alpha-helix to beta
      strand was observed.

PMID- 16443649
TI  - Reactive oxygen species inactivation of surfactant involves structural and
      functional alterations to surfactant proteins SP-B and SP-C.
AB  - Exposing bovine lipid extract surfactant (BLES), a clinical surfactant, to
      reactive oxygen species arising from hypochlorous acid or the Fenton reaction
      resulted in an increase in lipid (conjugated dienes, lipid aldehydes) and protein
      (carbonyls) oxidation products and a reduction in surface activity. Experiments
      where oxidized phospholipids (PL) were mixed with BLES demonstrated that this
      addition hampered BLES biophysical activity. However the effects were only
      moderately greater than with control PL. These results imply a critical role for
      protein oxidation. BLES oxidation by either method resulted in alterations in
      surfactant proteins SP-B and SP-C, as evidenced by altered Coomassie blue and
      silver staining. Western blot analyses showed depressed reactivity with specific
      antibodies. Oxidized SP-C showed decreased palmitoylation. Reconstitution
      experiments employing PL, SP-B, and SP-C isolated from control or oxidized BLES
      demonstrated that protein oxidation was more deleterious than lipid oxidation.
      Furthermore, addition of control SP-B can improve samples containing oxidized SP
      C, but not vice versa. We conclude that surfactant oxidation arising from
      reactive oxygen species generated by air pollution or leukocytes interferes with
      surfactant function through oxidation of surfactant PL and proteins, but that
      protein oxidation, in particular SP-B modification, produces the major
      deleterious effects.

PMID- 16443650
TI  - Conformational change of bacteriorhodopsin quantitatively monitored by
      microcantilever sensors.
AB  - Bacteriorhodopsin proteoliposomes were used as a model system to explore the
      applicability of micromechanical cantilever arrays to detect conformational
      changes in membrane protein patches. The three main results of our study concern:
      1), reliable functionalization of micromechanical cantilever arrays with
      proteoliposomes using ink jet spotting; 2), successful detection of the
      prosthetic retinal removal (bleaching) from the bacteriorhodopsin protein by
      measuring the induced nanomechanical surface stress change; and 3), the
      quantitative response thereof, which depends linearly on the amount of removed
      retinal. Our results show this technique to be a potential tool to measure
      membrane protein-based receptor-ligand interactions and conformational changes.

PMID- 16443651
TI  - Dynamics of the emission spectrum of a single LH2 complex: interplay of slow and
      fast nuclear motions.
AB  - We have studied the relationship between the realizations of static disorder and
      the emission spectra observed for a single LH2 complex. We show that the
      experimentally observed spectral fluctuations reflect realizations of the
      disorder in the B850 ring associated with different degrees of exciton
      delocalization and different effective coupling of the excitons to phonon modes.
      The main spectral features cannot be explained using models with correlated
      disorder associated with elliptical deformations of the ring. A quantitative
      explanation of the measured single-molecule spectra is obtained using the
      modified Redfield theory and a model of the B850 ring with uncorrelated disorder
      of the site energies. The positions and spectral shapes of the main exciton
      components in this model are determined by the disorder-induced shift of exciton
      eigenvalues in combination with phonon-induced effects (i.e., reorganization
      shift and broadening, that increase in proportion to the inverse delocalization
      length of the exciton state). Being dependent on the realization of the disorder,
      these factors produce different forms of the emission profile. In addition, the
      different degree of delocalization and effective couplings to phonons determines
      a different type of excitation dynamics for each of these realizations. We
      demonstrate that experimentally observed quasistable conformational states are
      characterized by excitation energy transfer regimes varying from a coherent
      wavelike motion of a delocalized exciton (with a 100-fs pass over half of the
      ring) to a hopping-type motion of the wavepacket (with a 350-fs jump between
      separated groups of 3-4 molecules) and self-trapped excitations that do not move
      from their localization site.

PMID- 16443652
TI  - Simulation-based methods for interpreting x-ray data from lipid bilayers.
AB  - The fully hydrated liquid crystalline phase of the dimyristoylphosphatidycholine
      lipid bilayer at 30 degrees C was simulated using molecular dynamics with the
      CHARMM potential for five surface areas per lipid (A) in the range 55-65 A(2)
      that brackets the previously determined experimental area 60.6 A(2). The results
      of these simulations are used to develop a new hybrid zero-baseline structural
      model, denoted H2, for the electron density profile, rho(z), for the purpose of
      interpreting x-ray diffraction data. H2 and also the older hybrid baseline model
      were tested by fitting to partial information from the simulation and various
      constraints, both of which correspond to those available experimentally. The A,
      rho(z), and F(q) obtained from the models agree with those calculated directly
      from simulation at each of the five areas, thereby validating this use of the
      models. The new H2 was then applied to experimental dimyristoylphosphatidycholine
      data; it yields A = 60.6 +/- 0.5 A(2), in agreement with the earlier estimate
      obtained using the hybrid baseline model. The electron density profiles also
      compare well, despite considerable differences in the functional forms of the two
      models. Overall, the simulated rho(z) at A = 60.7 A(2) agrees well with
      experiment, demonstrating the accuracy of the CHARMM lipid force field; small
      discrepancies indicate targets for improvements. Lastly, a simulation-based model
      free approach for obtaining A is proposed. It is based on interpolating the area
      that minimizes the difference between the experimental F(q) and simulated F(q)
      evaluated for a range of surface areas. This approach is independent of
      structural models and could be used to determine structural properties of
      bilayers with different lipids, cholesterol, and peptides.

PMID- 16443653
TI  - Laser-driven microsecond temperature cycles analyzed by fluorescence polarization
      microscopy.
AB  - We demonstrate a novel technique to achieve fast thermal cycles of a small sample
      (a few femtoliters). Modulating a continuous near-infrared laser focused on a
      metal film, we can drive the local temperature from 130 to 300 K and back, within
      a few microseconds. By fluorescence microscopy of dyes in a thin glycerol film,
      we record images of the hot spot, calibrate its temperature, and follow its
      variations in real time. The temperature dependence of fluorescence anisotropy,
      due to photophysics and rotational diffusion, gives a steady-state temperature
      calibration between 200 and 350 K. From 200 to 220 K, we monitor temperature more
      accurately by fluorescence autocorrelation, a probe for rotational diffusion.
      Time-resolved measurements of fluorescence anisotropy give heating and cooling
      times of a few microseconds, short enough to supercool pure water. We designed
      our method to repeatedly cycle a single (bio)molecule between ambient and
      cryostat temperatures with microsecond time resolution. Successive measurements
      of a structurally relevant variable will decompose a dynamical process into
      structural snapshots. Such temperature-cycle experiments, which combine a high
      time resolution with long observation times, can thus be expected to yield new
      insights into complex processes such as protein folding.

PMID- 16443654
TI  - Transport numbers in transdermal iontophoresis.
AB  - Parameters determining ionic transport numbers in transdermal iontophoresis have
      been characterized. The transport number of an ion (its ability to carry charge)
      is key to its iontophoretic delivery or extraction across the skin. Using small
      inorganic ions, the roles of molar fraction and mobility of the co- and
      counterions present have been demonstrated. A direct, constant current was
      applied across mammalian skin in vitro. Cations were anodally delivered from
      either simple M(+)Cl(-) solutions (single-ion case, M(+) = sodium, lithium,
      ammonium, potassium), or binary and quaternary mixtures thereof. Transport
      numbers were deduced from ion fluxes. In the single-ion case, maximum cationic
      fluxes directly related to the corresponding ionic aqueous mobilities were found.
      Addition of co-ions decreased the transport numbers of all cations relative to
      the single-ion case, the degree of effect depending upon the molar fraction and
      mobility of the species involved. With chloride as the principal counterion
      competing to carry current across the skin (the in vivo situation), a maximum
      limit on the single or collective cation transport number was 0.6-0.8. Overall,
      these results demonstrate how current flowing across the skin during transdermal
      iontophoresis is distributed between competing ions, and establish simple rules
      with which to optimize transdermal iontophoretic transport.

PMID- 16443655
TI  - Low amounts of sucrose are sufficient to depress the phase transition temperature
      of dry phosphatidylcholine, but not for lyoprotection of liposomes.
AB  - Disaccharides such as sucrose and trehalose play an important role in stabilizing
      cellular structures during dehydration. In fact, most organisms that are able to
      survive desiccation accumulate high concentrations of sugars in their cells. The
      mechanisms involved in the stabilization of cellular membranes in the dry state
      have been investigated using model membranes, such as phosphatidylcholine
      liposomes. It has been proposed that the lyoprotection of liposomes depends on
      the depression of the gel to liquid-crystalline phase transition temperature
      (T(m)) of the dry membranes below ambient and on the prevention of membrane
      fusion by sugar glass formation, because both lead to leakage of soluble content
      from the liposomes. Since fusion is prevented at lower sugar/lipid mass ratios
      than leakage, it has been assumed that more sugar is needed to depress T(m) than
      to prevent fusion. Here, we show that this is not the case. In air-dried egg
      phosphatidylcholine liposomes, T(m) is depressed by >60 degrees C at
      sucrose/lipid mass ratios 10-fold lower than those needed to depress fusion to
      below 20%. In fact, T(m) is significantly reduced at mass ratios where no bulk
      sugar glass phase is detectable by Fourier transform infrared spectroscopy or
      differential scanning calorimetry. A detailed analysis of the interactions of
      sucrose with the P=O, C=O, and choline groups of the lipid and a comparison to
      published data on water binding to phospholipids suggests that T(m) is reduced by
      sucrose through a "water replacement" mechanism. However, the sucrose/lipid mass
      ratios necessary to prevent leakage exceed those necessary to prevent both phase
      transitions and membrane fusion. We hypothesize that kinetic phenomena during
      dehydration and rehydration may be responsible for this discrepancy.

PMID- 16443656
TI  - Kinetics and thermodynamics of type VIII beta-turn formation: a CD, NMR, and
      microsecond explicit molecular dynamics study of the GDNP tetrapeptide.
AB  - We report an experimental and theoretical study on type VIII beta-turn using a
      designed peptide of sequence GDNP. CD and NMR studies reveal that this peptide
      exists in equilibrium between type VIII beta-turn and extended conformations.
      Extensive MD simulations give a description of the free energy landscape of the
      peptide in which we retrieve the same two main conformations suggested by the
      experiments. The free energy difference between the two conformational states is
      very small and the transition between them occurs within a few kT at 300 K on a
      nanosecond timescale. The equilibrium is mainly driven by entropic contribution,
      which favors extended conformations over beta-turns. This confirms other
      theoretical studies showing that beta-turns are marginally stable in water
      solution because of the larger entropy of the extended state unless some
      stabilizing interactions exist. Our observations may be extended to any type of
      beta-turn and have important consequences for protein folding. A comparison of
      our MD and CD results also suggests a possible type VIII beta-turn CD signature
      indicated by one main band at 200 nm, close to that of random coil, and a fairly
      large shoulder at 220 nm. Last, our results clearly show that the XXXP motif can
      only fold into a type VIII beta-turn, which is consistent with its fairly strong
      propensity for this type of turn. This important finding may help for peptide
      design and is in line with recent studies on bioactive elastin peptides.

PMID- 16443657
TI  - The SNARE motif is essential for the formation of syntaxin clusters in the plasma
      membrane.
AB  - In the plasma membrane, syntaxin 1 and syntaxin 4 clusters define sites at which
      secretory granules and caveolae fuse, respectively. It is widely believed that
      lipid phases are mandatory for cluster formation, as cluster integrity depends on
      cholesterol. Here we report that the native lipid environment is not sufficient
      for correct syntaxin 1 clustering and that additional cytoplasmic protein-protein
      interactions, primarily involving the SNARE motif, are required. Apparently no
      specific cofactors are needed because i), clusters form equally well in
      nonneuronal cells, and ii), as revealed by nanoscale subdiffraction resolution
      provided by STED microscopy, the number of clusters directly depends on the
      syntaxin 1 concentration. For syntaxin 4 clustering the N-terminal domain and the
      linker region are also dispensable. Moreover, clustering is specific because in
      both cluster types syntaxins mutually exclude one another at endogenous levels.
      We suggest that the SNARE motifs of syntaxin 1 and 4 mediate specific syntaxin
      clustering by homooligomerization, thereby spatially separating sites for
      different biological activities. Thus, syntaxin clustering represents a mechanism
      of membrane patterning that is based on protein-protein interactions.

PMID- 16443658
TI  - Salting the charged surface: pH and salt dependence of protein G B1 stability.
AB  - This study shows significant effects of protein surface charges on stability and
      these effects are not eliminated by salt screening. The stability for a variant
      of protein G B1 domain was studied in the pH-range of 1.5-11 at low, 0.15 M, and
      2 M salt. The variant has three mutations, T2Q, N8D, and N37D, to guarantee an
      intact covalent chain at all pH values. The stability of the protein shows
      distinct pH dependence with the highest stability close to the isoelectric point.
      The stability is pH-dependent at all three NaCl concentrations, indicating that
      interactions involving charged residues are important at all three conditions. We
      find that 2 M salt stabilizes the protein at low pH (protein net charge is +6 and
      total number of charges is 6) but not at high pH (net charge is <or=-6 and total
      number of charges is >or=18). Furthermore, 0.15 M salt slightly decreases the
      stability of the protein over the pH range. The results show that a net charge of
      the protein is destabilizing and indicate that proteins contain charges for
      reasons other than improved stability. Salt seems to reduce the electrostatic
      contributions to stability under conditions with few total charges, but cannot
      eliminate electrostatic effects in highly charged systems.

PMID- 16443659
TI  - Lignin radicals in the plant cell wall probed by Kerr-gated resonance Raman
      spectroscopy.
AB  - Lignin radicals are crucial intermediates for lignin biosynthesis in the cell
      wall of vascular plants. In this work they were for the first time, to our
      knowledge, selectively observed in wood cell walls by laser-based Kerr-gated
      resonance Raman spectroscopy, and the observations were supported by density
      functional theory prediction of their vibrational properties. For dry wood cells
      a lignin radical Raman band is observed at 1,570 cm(-1) irrespective of species.
      For wet beech cells they were generated in situ and observed at 1,606 cm(-1).
      DFT/B3LYP/6-31+G(d) modeling results support that in beech they are formed from
      syringyl (S) phenolic moieties and in spruce from guaiacyl (G) phenolic moieties.
      The observed lignin radical band is predicted as G is approximately 1,597 cm(-1)
      and S is approximately 1,599 cm(-1), respectively, and is assigned the (Wilson
      notation) nu(8a) phenyl ring mode. The RR band probes lignin radical properties,
      e.g., spin density distribution, and these respond to charge polarization or
      hydrogen bonding to proximate water molecules. These observations can be crucial
      for an understanding of the factors that control cell wall structure during
      biosynthesis of vascular plants and demonstrate the unique potential of RR
      spectroscopy of lignin radicals.

PMID- 16443660
TI  - Force microscopy of nonadherent cells: a comparison of leukemia cell
      deformability.
AB  - Atomic force microscopy (AFM) has become an important tool for quantifying
      mechanical properties of biological materials ranging from single molecules to
      cells and tissues. Current AFM techniques for measuring elastic and viscoelastic
      properties of whole cells are based on indentation of cells firmly adhered to a
      substrate, but these techniques are not appropriate for probing nonadherent
      cells, such as passive human leukocytes, due to a lateral instability of the
      cells under load. Here we present a method for characterizing nonadherent cells
      with AFM by mechanically immobilizing them in microfabricated wells. We apply
      this technique to compare the deformability of human myeloid and lymphoid
      leukemia cells and neutrophils at low deformation rates, and we find that the
      cells are well described by an elastic model based on Hertzian mechanics. Myeloid
      (HL60) cells were measured to be a factor of 18 times stiffer than lymphoid
      (Jurkat) cells and six times stiffer than human neutrophils on average
      (E(infinity) = 855 +/- 670 Pa for HL60 cells, E(infinity) = 48 +/- 35 Pa for
      Jurkat cells, E(infinity) = 156 +/- 87 for neutrophils, mean +/- SD). This work
      demonstrates a simple method for extending AFM mechanical property measurements
      to nonadherent cells and characterizes properties of human leukemia cells that
      may contribute to leukostasis, a complication associated with acute leukemia.

PMID- 16443661
TI  - A coarse-grained model for force-induced protein deformation and kinetics.
AB  - Force-induced changes in protein conformation are thought to be responsible for
      certain cellular responses to mechanical force. Changes in conformation
      subsequently initiate a biochemical response by alterations in, for example,
      binding affinity to another protein or enzymatic activity. Here, a model of
      protein extension under external forcing is created inspired by Kramers' theory
      for reaction rate kinetics in liquids. The protein is assumed to have two
      distinct conformational states: a relaxed state, C(1), preferred in the absence
      of external force, and an extended state, C(2), favored under force application.
      In the context of mechanotransduction, the extended state is a conformation from
      which the protein can initiate signaling. Appearance and persistence of C(2) are
      assumed to lead to transduction of the mechanical signal into a chemical one. The
      protein energy landscape is represented by two harmonic wells of stiffness
      kappa(1) and kappa(2), whose minima correspond to conformations C(1) and C(2).
      First passage time t(f) from C(1) to C(2) is determined from the Fokker-Plank
      equation employing several different approaches found in the literature. These
      various approaches exhibit significant differences in behavior as force
      increases. Although the level of applied force and the energy difference between
      states largely determine equilibrium, the dominant influence on t(f) is the
      height of the transition state. Distortions in the energy landscape due to force
      can also have a significant influence, however, exhibiting a weaker force
      dependence than exponential as previously reported, approaching a nearly constant
      value at a level of force that depends on the ratio kappa(1)/kappa(2). Two model
      systems are used to demonstrate the utility of this approach: a short alpha-helix
      undergoing a transition between two well-defined states and a simple molecular
      motor.

PMID- 16443662
TI  - Diatom adhesive mucilage contains distinct supramolecular assemblies of a single
      modular protein.
AB  - A previous study used atomic force microscopy saw-tooth retraction curves to
      characterize the adhesive mucilage pads of the diatom Toxarium undulatum. The
      major mucilage component consisted of adhesive nanofibers (ANFs) made up of
      modular proteins arranged into cohesive units, each containing a set number of
      modular proteins aligned in parallel. This study shows that T. undulatum adhesive
      mucilage is a biocomposite containing four additional adhesive components,
      including single modular proteins that are likely to be the structural units from
      which the ANFs are assembled. Two further distinct supramolecular assemblies were
      observed to coexist with ANFs (ANFs II and III), along with a continuum of single
      modular proteins through oligomers made up of varying numbers of modular proteins
      arranged in parallel. All components of the adhesive biocomposite produce a
      characteristic force spectrum with the same interpeak distance (35.3 +/- 0.3
      (mean +/- SE) nm), suggesting they are derived from discrete supramolecular
      assemblies of the same modular protein, but they are distinguishable from one
      another based on the rupture force, persistence length, and interpeak force
      measured from their saw-tooth curves.

PMID- 16443663
TI  - Solutes modify a conformational transition in a membrane transport protein.
AB  - The bacterial outer-membrane vitamin B(12) transporter, BtuB, undergoes a
      dramatic order-to-disorder transition in its N-terminal energy-coupling motif
      (Ton box) upon substrate binding. Here, site-directed spin labeling (SDSL) is
      used to show that a range of solutes prevents this conformational change when
      ligand is bound to BtuB, resulting in a more ordered Ton box structure. For each
      solute examined, the data indicate that solutes effectively block this
      conformational transition through an osmotic mechanism. The molecular weight
      dependence of this solute effect has been examined for a series of polyethylene
      glycols, and a sharp molecular weight cutoff is observed. This cutoff indicates
      that solutes are preferentially excluded from a cavity within the protein as well
      as the protein surface. Furthermore, the sensitivity of the conformational change
      to solution osmolality is consistent with a structural model predicted by SDSL.
      When the Ton box is unfolded by detergents or mutations (rather than by ligand
      binding), solutes, such as polyethylene glycols and salts, also induce a more
      structured compacted conformation. These results suggest that conformational
      changes in this class of outer membrane transporters, which involve modest energy
      differences and changes in hydration, may be modulated by a range of solutes,
      including solutes typically used in protein crystallization.

PMID- 16443664
TI  - Troponin T modulates sarcomere length-dependent recruitment of cross-bridges in
      cardiac muscle.
AB  - The heterogenic nature of troponin T (TnT) isoforms in fast skeletal and cardiac
      muscle suggests important functional differences. Dynamic features of rat cardiac
      TnT (cTnT) and rat fast skeletal TnT (fsTnT) reconstituted cardiac muscle
      preparations were captured by fitting the force response of small amplitude
      (0.5%) muscle length changes to the recruitment-distortion model. The recruitment
      of force-bearing cross-bridges (XBs) by increases in muscle length was favored by
      cTnT. The recruitment magnitude was approximately 1.5 times greater for cTnT-
      than for fsTnT-reconstituted muscle fibers. The speed of length-mediated XB
      recruitment (b) in cTnT-reconstituted muscle fiber was 0.50-0.57 times as fast as
      fsTnT-reconstituted muscle fibers (3.05 vs. 5.32 s(-1) at sarcomere length, SL,
      of 1.9 microm and 4.16 vs. 8.36 s(-1) at SL of 2.2 microm). Due to slowing of b
      in cTnT-reconstituted muscle fibers, the frequency of minimum stiffness (f(min))
      was shifted to lower frequencies of muscle length changes (at SL of 1.9 microm,
      0.64 Hz, and 1.16 Hz for cTnT- and fsTnT-reconstituted muscle fibers,
      respectively; at SL of 2.2 microm, 0.79 Hz, and 1.11 Hz for cTnT- and fsTnT
      reconstituted muscle fibers, respectively). Our model simulation of the data
      implicates TnT as a participant in the process by which SL- and XB-regulatory
      unit cooperative interactions activate thin filaments. Our data suggest that the
      amino-acid sequence differences in cTnT may confer a heart-specific regulatory
      role. cTnT may participate in tuning the heart muscle by decreasing the speed of
      XB recruitment so that the heart beats at a rate commensurate with f(min).

PMID- 16443665
TI  - Synthesis of voltage-sensitive optical signals: application to panoramic optical
      mapping.
AB  - Fluorescent photon scattering is known to distort optical recordings of cardiac
      transmembrane potentials; however, this process is not well quantified, hampering
      interpretation of experimental data. This study presents a novel model, which
      accurately synthesizes fluorescent recordings over the irregular geometry of the
      rabbit ventricles. Using the model, the study aims to provide quantification of
      fluorescent signal distortion for different optical characteristics of the
      preparation and of the surrounding medium. A bi-domain representation of
      electrical activity is combined with finite element solutions to the photon
      diffusion equation simulating both the excitation and emission processes, along
      with physically realistic boundary conditions at the epicardium, which allow
      simulation of different experimental setups. We demonstrate that distortion in
      the optical signal as a result of fluorescent photon scattering is truly a three
      dimensional phenomenon and depends critically upon the geometry of the
      preparation, the scattering properties of the tissue, the direction of wavefront
      propagation, and the specifics of the experimental setup. Importantly, we show
      that in an anatomically accurate model of ventricular geometry and fiber
      orientation, the morphology of the optical signal does not provide reliable
      information regarding the intramural direction of wavefront propagation. These
      findings underscore the potential of the new model in interpreting experimental
      data.

PMID- 16443666
TI  - Investigation of drug-drug interaction potential of bortezomib in vivo in female
      Sprague-Dawley rats and in vitro in human liver microsomes.
AB  - Bortezomib (Velcade, PS-341), a dipeptidyl boronic acid, is a first-in-class
      proteasome inhibitor approved in 2003 for the treatment of multiple myeloma. In a
      preclinical toxicology study, bortezomib-treated rats resulted in liver
      enlargement (35%). Ex vivo analyses of the liver samples showed an 18% decrease
      in cytochrome P450 (P450) content, a 60% increase in palmitoyl coenzyme A beta
      oxidation activity, and a 41 and 23% decrease in CYP3A protein expression and
      activity, respectively. Furthermore, liver samples of bortezomib-treated rats had
      little change in CYP2B and CYP4A protein levels and activities. To address the
      likelihood of clinical drug-drug interactions, the P450 inhibition potential of
      bortezomib and its major deboronated metabolites M1 and M2 and their dealkylated
      metabolites M3 and M4 was evaluated in human liver microsomes for the major P450
      isoforms 1A2, 2C9, 2C19, 2D6, and 3A4/5. Bortezomib, M1, and M2 were found to be
      mild inhibitors of CYP2C19 (IC(50) approximately 18.0, 10.0, and 13.2 microM,
      respectively), and M1 was also a mild inhibitor of CYP2C9 (IC(50) approximately
      11.5 microM). However, bortezomib, M1, M2, M3, and M4 did not inhibit other P450s
      (IC(50) values > 30 microM). There also was no time-dependent inhibition of
      CYP3A4/5 by bortezomib or its major metabolites. Based on these results, no major
      P450-mediated clinical drug-drug interactions are anticipated for bortezomib or
      its major metabolites. To our knowledge, this is the first report on P450
      mediated drug-drug interaction potential of proteasome inhibitors or boronic acid
      containing therapeutics.

PMID- 16443668
TI  - The mitogen-activated protein kinase kinase (mek) inhibitor PD98059 elevates
      primary cultured rat hepatocyte glutathione levels independent of inhibiting mek.
AB  - The antioxidant activity of flavonoids, directly through scavenging oxidizing
      species and indirectly through modulating drug-metabolizing enzyme activities, is
      associated with chemopreventive and chemotherapeutic effects. However, little
      published information is available concerning the effect of flavonoids on
      glutathione (GSH) homeostasis. We previously demonstrated that PD98059 (2'-amino
      3'-methoxyflavone), a flavone derivative and selective mitogen-activated protein
      kinase kinase (MEK) 1 inhibitor, enhanced the insulin-mediated increase in GSH
      levels. To determine whether the PD98059-mediated increase in GSH levels was
      associated with MEK inhibition, primary cultured rat hepatocytes were treated
      with PD98059, the MEK inhibitor U0126, which is not a flavone derivative, or
      flavone. PD98059 increased GSH levels in a concentration-dependent manner in
      hepatocytes cultured in the presence or absence of insulin. In contrast, GSH
      levels were not affected by U0126 at concentrations sufficient to inhibit insulin
      mediated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation.
      Flavone, however, markedly increased GSH levels without inhibition of ERK1/2
      phosphorylation. The concentration of GSH in the culture medium was also elevated
      by PD98059 or flavone, suggesting that the cellular GSH elevation could not be
      accounted for by the inhibition of GSH efflux into medium. Interestingly, PD98059
      and flavone increased cellular cysteine levels, which may be responsible for the
      PD98059- and flavone-mediated elevation of GSH levels. These results provide
      evidence that PD98059 and flavone produce dramatic changes in GSH homeostasis in
      hepatocytes, through a mechanism(s) unrelated to MEK inhibition. Moreover, the
      current study implies that flavonoid-induced chemopreventive and chemotherapeutic
      effects may be mediated by regulation of redox state through the stimulation of
      GSH synthesis.

PMID- 16443667
TI  - Identification of human liver cytochrome P450 enzymes responsible for the
      metabolism of lonafarnib (Sarasar).
AB  - Lonafarnib (Sarasar), a farnesyl transferase inhibitor, is currently under
      development for the treatment of solid tumors. Incubation of lonafarnib with
      human liver microsomes resulted in the formation of four oxidative metabolites
      (M1, M2, M3, and M4). Minor to trace levels of these metabolites were detected in
      humans after multiple-dose administration of lonafarnib. Liquid chromatography
      mass spectrometry analyses exhibited a mass to charge ratio (m/z) for the
      (M+H)(+) ion of M1, M2, M3, and M4 at 653, 635, 669, and 653 Th, respectively.
      These metabolites, respectively, resulted from changes of +O, -2H, +2O, and +O
      relative to lonafarnib. Recombinant human CYP3A4 and CYP3A5 exhibited catalytic
      activity with respect to the formation of M1, M2, and M3, whereas CYP2C8
      exhibited catalytic activity with respect to the formation of M4. There was a
      high correlation between the formation of M1, determined in 10 human liver
      microsomal samples, and 6beta-hydroxylation of testosterone catalyzed by CYP3A4/5
      (r = 0.93). The IC(50) values of ketoconazole for inhibition of M1 and M2 were
      0.61 and 0.92 microM, respectively. The formation of M4 by human liver microsomes
      was inhibited 72% by 50 microM quercetin, suggesting that the formation of M4 was
      mediated via CYP2C8. A CYP3A4/5-specific inhibitory monoclonal antibody inhibited
      the formation of M1, M2, and M3 by 85, 75, and 100%, respectively. In conclusion,
      the formation of metabolites M1, M2, and M3 from lonafarnib was mediated via
      CYP3A4 and CYP3A5.

PMID- 16443670
TI  - Laser microdissection and pressure-catapulting technique to study gene expression
      in the reoxygenated myocardium.
AB  - For focal events such as myocardial infarction, it is important to dissect
      infarction-induced biological responses as a function of space with respect to
      the infarct core. Laser microdissection pressure catapulting (LMPC) represents a
      recent variant of laser capture microdissection that enables robot-assisted rapid
      capture of catapulted tissue without direct user contact. This work represents
      the maiden effort to apply laser capture microdissection to study spatially
      resolved biological responses in myocardial infarction. Infarcted areas of the
      surviving ischemic-reperfused murine heart were identified using a standardized
      hematoxylin QS staining procedure. Standard staining techniques fail to preserve
      tissue RNA. Exposure of the tissue to an aqueous medium (typically used during
      standard immunohistochemical staining), with or without RNase inhibitors,
      resulted in a rapid degradation of genes, with approximately 80% loss in the 1st
      h. Tissue elements (1 x 10(4)-4 x 10(6) microm(2)) captured from infarcted and
      noninfarcted sites with micrometer-level surgical precision were collected in a
      chaotropic RNA lysis solution. Isolated RNA was analyzed for quality by
      microfluidics technology and reverse transcribed to generate high-quality cDNA.
      Real-time PCR analysis of the cDNA showed marked (200- and 400-fold,
      respectively) induction of collagen Ia and IIIa at the infarcted site compared
      with the noninfarcted site. This work reports a sophisticated yet rapid approach
      to measurement of relative gene expressions from tissue elements captured from
      spatially resolved microscopic regions in the heart with micrometer-level
      precision.

PMID- 16443669
TI  - Fetal morphine metabolism and clearance are constant during late gestation.
AB  - Fetal metabolism significantly contributes to the clearance of drugs from the
      fetus. To understand how the changes in fetal metabolism expected in late
      gestation alter fetal drug clearance, serial measurements of morphine metabolism
      were made in the fetal baboon over the latter third of gestation. Clearance and
      metabolism were evaluated in the context of fetal growth, onset of labor, and the
      administration of classical enzyme induction agents. Morphine, a probe substrate
      for the enzyme uridine diphosphate glucuronosyltransferase 2B7 (UGT2B7), was
      continuously infused to chronically catheterized fetal baboons while measuring
      morphine, morphine-3-beta-glucuronide, and morphine-6-beta-glucuronide
      concentrations. In some animals, intermittent infusions of the metabolites
      provided estimates of metabolite clearance and, hence, the rate of formation of
      metabolites and metabolic clearance. Overall, metabolic clearance of morphine
      from the fetus was 27 +/- 9.0 ml x min(-1) or 32% of total clearance. This is
      similar to the overall clearance in the adult baboon when standardized to weight.
      No change in any measure of metabolism or clearance of morphine or its
      glucuronide metabolites was found with gestational age, the presence of labor, or
      administration of UGT enzyme induction agents. Interpreting these findings using
      a physiologically based approach suggests that the intrinsic clearance of the
      fetal liver toward morphine is of sufficient magnitude that fetal hepatic
      clearance is flow-limited. The implication of a high intrinsic clearance is for
      significant placento-hepatic first-pass metabolism when drugs are administered to
      the mother. The previously held view of the "inadequacy of perinatal
      glucuronidation" needs to be reconsidered.

PMID- 16443672
TI  - GPI-linked endothelial CD14 contributes to the detection of LPS.
AB  - The inflammatory endothelial response to LPS is critical to the host's surviving
      a gram-negative bacterial infection. In this study we investigated whether human
      endothelial cells express the functional coreceptor for LPS, CD14, and most
      importantly whether it is glycosylphosphatidylinositol (GPI) linked. We also
      examined whether plasma proteins could reconstitute an LPS response in CD14
      inhibited endothelium. RT-PCR- and CD14-specific MAbs demonstrated CD14
      expression on primary human umbilical vein endothelial cells (HUVEC) but not
      passaged HUVEC. The amino acid sequence of endothelial CD14 was 99% homologous to
      CD14 on monocytes. Endothelium responded to relatively low levels of LPS in the
      absence of plasma, and this was entirely dependent on CD14. Removal of GPI-linked
      proteins with phosphatidylinositol-phospholipase C prevented LPS detection and
      subsequent protein synthesis (E-selectin expression). Endothelial CD14 was
      sufficient to initiate functional leukocyte recruitment, an event inhibited by
      blocking its LPS binding epitope and also by removing CD14 from the endothelial
      surface. Plasma proteins restored only approximately 30% of the LPS response in
      CD14-inhibited endothelium. In conclusion, our results strongly support an
      important role for endothelial membrane CD14 in the activation of endothelium for
      leukocyte recruitment.

PMID- 16443671
TI  - Differential effects of saturated and unsaturated fatty acid diets on
      cardiomyocyte apoptosis, adipose distribution, and serum leptin.
AB  - Fatty acids are the primary fuel for the heart and are ligands for peroxisome
      proliferator-activated receptors (PPARs), which regulate the expression of genes
      encoding proteins involved in fatty acid metabolism. Saturated fatty acids,
      particularly palmitate, can be converted to the proapoptotic lipid intermediate
      ceramide. This study assessed cardiac function, expression of PPAR-regulated
      genes, and cardiomyocyte apoptosis in rats after 8 wk on either a low-fat diet
      [normal chow control (NC); 10% fat calories] or high-fat diets composed mainly of
      either saturated (Sat) or unsaturated fatty acids (Unsat) (60% fat calories) (n =
      10/group). The Sat group had lower plasma insulin and leptin concentrations
      compared with the NC or Unsat groups. Cardiac function and mass and body mass
      were not different. Cardiac triglyceride content was increased in the Sat and
      Unsat groups compared with NC (P < 0.05); however, ceramide content was higher in
      the Sat group compared with the Unsat group (2.9 +/- 0.2 vs. 1.4 +/- 0.2 nmol/g;
      P < 0.05), whereas the NC group was intermediate (2.3 +/- 0.3 nmol/g). The number
      of apoptotic myocytes, assessed by terminal deoxynucleotide transferase-mediated
      dUTP nick-end labeling staining, was higher in the Sat group compared with the
      Unsat group (0.28 +/- 0.05 vs. 0.17 +/- 0.04 apoptotic cells/1,000 nuclei; P <
      0.04) and was positively correlated to ceramide content (P < 0.02). Both high-fat
      diets increased the myocardial mRNA expression of the PPAR-regulated genes
      encoding uncoupling protein-3 and pyruvate dehydrogenase kinase-4, but only the
      Sat diet upregulated medium-chain acyl-CoA dehydrogenase. In conclusion, dietary
      fatty acid composition affects cardiac ceramide accumulation, cardiomyocyte
      apoptosis, and expression of PPAR-regulated genes independent of cardiac mass or
      function.

PMID- 16443673
TI  - Inhaled nitric oxide decreases infarction size and improves left ventricular
      function in a murine model of myocardial ischemia-reperfusion injury.
AB  - To learn whether nitric oxide (NO) inhalation can decrease myocardial ischemia
      reperfusion (I/R) injury, we studied a murine model of myocardial infarction
      (MI). Anesthetized mice underwent left anterior descending coronary artery
      ligation for 30, 60, or 120 min followed by reperfusion. Mice breathed NO
      beginning 20 min before reperfusion and continuing thereafter for 24 h. MI size
      and area at risk were measured, and left ventricular (LV) function was evaluated
      using echocardiography and invasive hemodynamic measurements. Inhalation of 40 or
      80 ppm, but not 20 ppm, NO decreased the ratio of MI size to area at risk. NO
      inhalation improved LV systolic function, as assessed by echocardiography 24 h
      after reperfusion, and systolic and diastolic function, as evaluated by
      hemodynamic measurements 72 h after reperfusion. Myocardial neutrophil
      infiltration was reduced in mice breathing NO, and neutrophil depletion prevented
      inhaled NO from reducing myocardial I/R injury. NO inhalation increased arterial
      nitrite levels but did not change myocardial cGMP levels. Breathing 40 or 80 ppm
      NO markedly and significantly decreased MI size and improved LV function after
      ischemia and reperfusion in mice. NO inhalation may represent a novel method to
      salvage myocardium at risk of I/R injury.

PMID- 16443674
TI  - Inhibition of sickle red cell adhesion and vasoocclusion in the microcirculation
      by antioxidants.
AB  - In sickle cell anemia (SCA), inflammatory (i.e., intravascular sickling and
      transient vasoocclusive) events result in chronic endothelial activation. In
      addition to sickling behavior, sickle (SS) red blood cells exhibit abnormal
      interaction with the vascular endothelium, which is considered to have an
      important role in initiation of vasoocclusion. Upregulation of endothelial
      adhesion molecules caused by oxidants (and cytokines) may lead to increased SS
      red cell adhesion. We hypothesize that endothelial activation is indispensable in
      SS red cell adhesion to the endothelium and that antioxidants will have an
      inhibitory effect on this interaction. We examined the effect of selected
      antioxidants in ex vivo mesocecum vasculature, a well-established model that
      allows measurement of hemodynamic parameters and, by intravital microscopy, can
      allow quantification of adhesion. We tested antioxidant enzymes (SOD and
      catalase) and an intravascular SOD mimetic, polynitroxyl albumin (PNA), in the
      presence of platelet-activating factor (PAF); the latter causes endothelial
      oxidant generation and endothelial activation, which characterize SCA. In ex vivo
      preparations, PAF not only induced marked endothelial oxidant generation, it also
      enhanced SS red cell adhesion, resulting in frequent blockage of small-diameter
      venules. The adhesion, inversely related to venular diameter, and vasoocclusion
      were markedly inhibited by antioxidants, resulting in improved hemodynamics. PNA,
      the most effective antioxidant, also abolished SS red cell adhesion in non-PAF
      activated preparations. Thus SS red cell adhesion and related vasoocclusion may
      be ameliorated by antioxidant therapy with a stable and long-acting molecule
      (e.g., PNA).

PMID- 16443675
TI  - Evidence for the involvement of myoendothelial gap junctions in EDHF-mediated
      relaxation in the rat middle cerebral artery.
AB  - The mechanisms underlying endothelium-dependent hyperpolarizing factor (EDHF) in
      the middle cerebral artery (MCA) remain largely unresolved. In particular, very
      little is known regarding the way in which the signal is transmitted from
      endothelium to smooth muscle. The present study tested the hypothesis that direct
      communication via myoendothelial gap junctions contributes to the EDHF response
      in the male rat MCA. EDHF-mediated dilations were elicited in rat MCAs by luminal
      application of ATP or UTP in the presence of Nomega-nitro-L-arginine methyl ester
      and indomethacin. Maximum dilation to luminal ATP (10(-4) M) was reduced
      significantly after incubation with a gap peptide cocktail (9 +/- 4%, n = 6)
      compared with a scrambled gap peptide cocktail (99 +/- 1%, n = 6, P < 0.05). A
      gap peptide cocktail had no effect on amplitude of endothelial cell
      hyperpolarization in response to 3 x 10(-5) M UTP (22 +/- 3 vs. 22 +/- 1 mV, n =
      4), whereas smooth muscle cell hyperpolarization was significantly attenuated (17
      +/- 1 vs. 6 +/- 1 mV, n = 4, P = 0.004). Connexin (Cx) 37 was localized to smooth
      muscle and Cx43 to endothelium, whereas Cx40 was found in endothelium and smooth
      muscle. Electron microscopy revealed the existence of frequent myoendothelial
      junctions. The total number of myoendothelial junctions per 5 microm of MCA
      sectioned was 2.5 +/- 0.5. Our results suggest that myoendothelial communication
      contributes to smooth muscle cell hyperpolarization and EDHF dilation in male rat
      MCA.

PMID- 16443676
TI  - Effects of high-sucrose feeding on insulin resistance and hemodynamic responses
      to insulin in spontaneously hypertensive rats.
AB  - This study was designed to investigate the effects of a sucrose diet on vascular
      and metabolic actions of insulin in spontaneously hypertensive rats (SHR). Male
      SHR were randomized to receive a sucrose or regular chow diet for 4 wk. Age
      matched, chow-fed Wistar-Kyoto (WKY) rats were used as normotensive control. In a
      first series of experiments, the three groups of rats had pulsed Doppler flow
      probes and intravascular catheters implanted to determine blood pressure, heart
      rate, and blood flows. Insulin sensitivity was assessed during a euglycemic
      hyperinsulinemic clamp performed in conscious rats. In a second series of
      experiments, new groups of rats were used to examine glucose transport activity
      in isolated muscles and to determine endothelial nitric oxide synthase (eNOS)
      protein expression in muscles and endothelin content in vascular tissues. Sucrose
      feeding was shown to markedly enhance the pressor response to insulin and its
      hindquarter vasoconstrictor effect when compared with chow-fed SHR. A reduction
      in eNOS protein content in muscle, but no change in vascular endothelin-1
      protein, was noted in sucrose-fed SHR when compared with WKY rats, but these
      changes were not different from those noted in chow-fed SHR. Similar reductions
      in insulin-stimulated glucose transport were observed in soleus muscles from both
      groups of SHR when compared with WKY rats. In extensor digitorum longus muscles,
      a significant reduction in insulin-stimulated glucose transport was only seen in
      sucrose-fed rats when compared with the other two groups. Environmental factors,
      that is, high intake of simple sugars, could possibly potentiate the genetic
      predisposition in SHR to endothelial dysfunction and insulin resistance.

PMID- 16443677
TI  - Gene transfer of extracellular superoxide dismutase protects against vascular
      dysfunction with aging.
AB  - Aging is an independent risk factor for cardiovascular disease, but mechanisms
      leading to vascular dysfunction have not been fully elucidated. Recent studies
      suggest that oxidative stress may increase in blood vessels during aging. Levels
      of superoxide are influenced by the activity of SODs. The goal of this study was
      to examine the effect of extracellular superoxide dismutase (ECSOD) on superoxide
      levels and vascular function in an animal model of aging. Aortas from young (4-8
      mo old) and old (29-31 mo old) Fischer 344 rats were examined in vitro.
      Relaxation of aorta to ACh was impaired in old rats compared with young rats;
      e.g., 3 muM ACh produced 57 +/- 4% (mean +/- SE) and 84 +/- 2% relaxation in old
      and young rats, respectively (P < 0.0001). Three days after gene transfer of
      adenovirus expressing human ECSOD (AdECSOD), the response to ACh was not affected
      in young rats but was improved in old rats. There was no difference in relaxation
      to the endothelium-independent dilator sodium nitroprusside between young, aged,
      and AdECSOD-treated old rats. Superoxide levels (lucigenin-enhanced
      chemiluminescence) were significantly increased in aged rats compared with young
      rats. After gene transfer of ECSOD to aged rats, superoxide levels in aorta were
      similar in old and young rats. Gene transfer of an ECSOD with the heparin-binding
      domain deleted had no effect on vascular function or superoxide levels in old
      rats. These results suggest that 1) vascular dysfunction associated with aging is
      mediated in part by increased levels of superoxide, 2) gene transfer of ECSOD
      reduces vascular superoxide and dysfunction in old rats, and 3) beneficial
      effects of ECSOD in old rats require the heparin-binding domain of ECSOD.

PMID- 16443678
TI  - Evaluation of frequency, type, and function of gap junctions between skeletal
      myoblasts overexpressing connexin43 and cardiomyocytes: relevance to cell
      transplantation.
AB  - Cell transplantation of skeletal myoblasts (SMs) is one possible treatment for
      repairing cardiac tissue after myocardial injury. However, inappropriate
      electrical coupling between grafted SMs and host cardiomyocytes may be
      responsible for the arrhythmias observed in clinical trials of SM
      transplantation. Whether functional gap junctions occur between the two cell
      types remains controversial. We have studied the ability of SMs to electrically
      couple with isolated adult rat cardiomyocytes (CMs) and assessed whether
      connexin43 (Cx43) overexpression enhanced gap junctional conductance (Gj). C2C12
      myoblast lines overexpressing Cx43 were generated by gene transfection and clonal
      selection. CMs were cocultured with either SMs overexpressing Cx43 (CM-SM(Cx43))
      or control SMs (CM-SM(WT)) in vitro. Gj between pairs of SMs and CMs was
      quantified with dual whole cell patch clamping. Formation of Gj occurred between
      22% of CM-SM(WT) pairs (n=73) and 48% of CM-SM(Cx43) pairs (n=71, P<0.001). The
      Gj of CM-SM(Cx43) pairs (29.7+/-4.3 nS, n=21) was greater than that of CM-SM(WT)
      pairs (14.8+/-2.0 nS, n=12, P<0.05). The overexpression of Cx43 in SMs increased
      the formation of electrical communication and the steady-state conductance
      between SMs and CMs. Enhanced gap junctional conductance may be useful to promote
      the integration of transplanted SMs into the myocardium.

PMID- 16443679
TI  - Intracellular targeting of truncated secretory peptides in the mammalian heart
      and brain.
AB  - Secretory polypeptides are vital for nervous system function, sleep,
      reproduction, growth, and metabolism. Ribosomes scanning the 5'-end of mRNA
      usually detect the first AUG site for initiating translation. The nascent
      propeptide chain is then directed via a signal-peptide into the endoplasmic
      reticulum, processed through the Golgi stacks, and packaged into secretory
      vesicles. By expressing prepropeptide-EGFP fusion proteins, we observed unusual
      destinations, mitochondria, nucleus, and cytoplasm, of neuropeptide Y (NPY),
      atrial natriuretic peptide, and growth hormone in living murine cardiac cells and
      hypothalamic slices. Subcellular expression was modulated by Zn++ or mutations of
      N-terminal prohormone sequences but was not due to overexpression in the trans
      Golgi network. Mitochondrial targeting of NPY also occurred without the EGFP tag,
      was enhanced by site-directed mutagenesis of the first AUG initiation site, and
      abolished by mutation of the second AUG. Immunological methods indicated the
      presence of N-terminal truncated NPY in mitochondria. Imaging studies showed
      depolarization of NPY-containing mitochondria. P-SORT software correctly
      predicted the secondary intracellular destinations and suggested such
      destinations for many neuropeptides and peptide hormones known. Thus, mammalian
      cells may retarget secretory peptides from extracellular to intracellular sites
      by skipping the first translation-initiation codon and thereby alter
      mitochondrial function, gene expression, and secretion.

PMID- 16443680
TI  - Development of CD4+ T cells expressing a nominally MHC class I-restricted T cell
      receptor by two different mechanisms.
AB  - Differences in T cell receptor (TCR) signaling initiated by interactions among
      TCRs, coreceptors, and self-peptide-MHC complexes determine the outcome of CD4
      versus CD8 lineage of T cell differentiation. The H-2Ld and Kbm3 alloreactive 2C
      TCR is positively selected by MHC class I Kb and a yet-to-be identified
      nonclassical class I molecule to differentiate into CD8+ T cells. Here we
      describe two mechanisms by which CD4+ 2C T cells can be generated in 2C TCR
      transgenic mice. In the RAG-/- background, development of CD4+ 2C T cells
      requires the expression of both I-Ab and the TAP genes, indicating that both MHC
      class I and II molecules are required for positive selection of these T cells.
      Notably, only some of the 2C+ RAG-/- mice (approximately 30%) develop CD4+ 2C T
      cells, with frequencies in individual mice varying from 0.5% to as high as
      approximately 50%. In the RAG+ background, where endogenous TCRalpha genes are
      rearranged and expressed, CD4+ 2C T cells are generated because these cells
      express the 2C TCR as well as additional TCRs, consisting of the 2C TCRbeta and
      endogenous TCRalpha chains. Similarly, T cells expressing the OT-1 TCR, which is
      nominally MHC class I-restricted, can also develop into CD4+ T cells through the
      same two mechanisms. Thus, expression of two TCRs by a single thymocyte, TCR
      recognition of multiple MHC molecules, and heterogeneity of TCR, coreceptors, and
      peptide-MHC interactions in the thymus all contribute to the outcome of CD4
      versus CD8 lineage development.

PMID- 16443682
TI  - Transposable elements have contributed to thousands of human proteins.
AB  - This is a report of many distant but significant protein sequence relationships
      between human proteins and transposable elements (TEs). The libraries of human
      repeated sequences contain the DNA sequences of many TEs. These were translated
      in all reading frames, ignoring stop codons, and were used as amino acid sequence
      probes to search with BLASTP for similar sequences in a library of 25,193 human
      proteins. The probes show regions of significant amino acid sequence similarity
      to 1,950 different human genes, with an expectation of <10(-3). In comparison
      with previous REPEATMASKER (Institute for Systems Biology, Seattle) studies,
      these probes detect many more TE sequences in more human coding sequences with
      greater length than previous work using DNA sequences. If the criterion is
      opened, very many matches are found occurring on 4,653 different genes after
      correction for the number seen with random amino acid sequence probes. The
      processes that led to these extensive sets of sequence relationships between TEs
      and coding sequences of human genes have been a major source of variation and
      novel genes during evolution. This paper lists the number of sequence
      similarities seen by amino acid sequence comparison, which is surely an
      underestimate of the actual number of significant relationships. It appears that
      many of these are the result of past events of duplication of genes or gene
      regions, rather than a direct result of TE insertion. This report of observable
      relationships leaves to the future the functional implications as well as the
      detection of the events of TE insertion.

PMID- 16443681
TI  - Age-dependent cell death and the role of ATP in hydrogen peroxide-induced
      apoptosis and necrosis.
AB  - Cell death plays a pivotal role in the body to maintain homeostasis during aging.
      Studies have shown that damaged cells, which must be removed from the body,
      accumulate during aging. Decay of the capacity and/or control of cell death
      during aging is widely considered to be involved in some age-dependent diseases.
      We investigated the accumulation of protein carbonyls and the role of cell death
      induced by hydrogen peroxide in human fibroblasts from individuals of various
      ages (17-80 years). The results showed that levels of oxidatively modified
      proteins increased with age, not only in whole-cell lysates but also in
      mitochondrial fractions, and this change correlates with a decline in the
      intracellular ATP level. Exposure of fibroblasts to hydrogen peroxide led to cell
      death by apoptosis and necrosis. Younger (<60 years old) cells were more
      resistant to necrosis induced by hydrogen peroxide than were older cells (>60
      years old), which contained lower levels of free ATP than did younger cells.
      Treatment of cells of all ages with inhibitors of ATP synthesis (oligomycin, 2,4
      dinitrophenol, or 2-deoxyglucose) made them more susceptible to cell death but
      also led to a switch in the death mode from apoptosis to necrosis. Furthermore,
      hydrogen peroxide treatment led to a greater accumulation of several inflammatory
      cytokines (IL-6, IL-7, IL-16, and IL-17) and increased necrosis in older cells.
      These results suggest that age-related decline in the ATP level reduces the
      capacity to induce apoptosis and promotes necrotic inflammation. This switch may
      trigger a number of age-dependent disorders.

PMID- 16443683
TI  - Transcriptome of Salmonella enterica serovar Typhi within macrophages revealed
      through the selective capture of transcribed sequences.
AB  - The cDNA obtained by selective capture of transcribed sequences is a complex
      mixture that can be used in conjunction with microarrays to determine global gene
      expression by a pathogen during infection. We used this method to study genes
      expressed by Salmonella enterica serovar Typhi, the etiological agent of typhoid
      fever, within human macrophages. Global expression profiles of Typhi grown in
      vitro and within macrophages at different time points were obtained and compared.
      Known virulence factors, such as the SPI-1- and SPI-2-encoded type III secretion
      systems, were found to be expressed as predicted during infection by Salmonella,
      which validated our data. Typhi inside macrophages showed increased expression of
      genes encoding resistance to antimicrobial peptides, used the glyoxylate bypass
      for fatty acid utilization, and did not induce the SOS response or the oxidative
      stress response. Genes coding for the flagellar apparatus, chemotaxis, and iron
      transport systems were down-regulated in vivo. Many cDNAs corresponding to genes
      with unknown functions were up-regulated inside human macrophages and will be
      important to consider for future studies to elucidate the intracellular lifestyle
      of this human-specific pathogen. Real-time quantitative PCR was consistent with
      the microarray results. The combined use of selective capture of transcribed
      sequences and microarrays is an effective way to determine the bacterial
      transcriptome in vivo and could be used to investigate transcriptional profiles
      of other bacterial pathogens without the need to recover many nanograms of
      bacterial mRNA from host and without increasing the multiplicity of infection
      beyond what is seen in nature.

PMID- 16443684
TI  - In vivo disruption of TGF-beta signaling by Smad7 leads to premalignant ductal
      lesions in the pancreas.
AB  - TGF-beta has been postulated to play an important role in the development of
      pancreatic cancers. More than 50% of human pancreatic cancers bear mutations of
      Sma- and Mad-related protein (Smad) 4, a critical protein required for TGF-beta
      signaling. To evaluate the in vivo function of TGF-beta in the development of
      pancreatic cancers, we generated a transgenic mouse model with pancreas-specific
      expression of Smad7, a specific inhibitor of TGF-beta signaling. Through the use
      of elastase I promoter, we directed the tissue specific expression of exogenous
      Smad7. Consistently, the exogenous Smad7 was detected only in the pancreas in the
      transgenic mice, and, furthermore, phosphorylation of Smad2 was blocked in the
      pancreatic tissues. At 6 months of age, most transgenic animals developed
      premalignant ductal lesions in the pancreas, with characteristics of pancreatic
      intraepithelial neoplasia (PanIN), a precursor to invasive pancreatic cancers.
      The premalignant lesions of the pancreas were accompanied by accelerated
      proliferation of the ductal epithelium and acinar cells, as well as increased
      fibrosis around the ductal lesions. This study not only demonstrated that in vivo
      inactivation of TGF-beta signaling is implicated in the development of early
      stage of pancreatic cancers, but also provided a promising animal model useful
      for the investigation and intervention of pancreatic cancers in humans.

PMID- 16443685
TI  - Historical contingency and the purported uniqueness of evolutionary innovations.
AB  - Many events in the history of life are thought to be singular, that is, without
      parallels, analogs, or homologs in time and space. These claims imply that
      history is profoundly contingent in that independent origins of life in the
      universe will spawn radically different histories. If, however, most innovations
      arose more than once on Earth, histories would be predictable and replicable at
      the scale of functional roles and directions of adaptive change. Times of origin
      of 23 purportedly unique evolutionary innovations are significantly more ancient
      than the times of first instantiation of 55 innovations that evolved more than
      once, implying that the early phases of life's history were less replicable than
      later phases or that the appearance of singularity results from information loss
      through time. Indirect support for information loss comes from the distribution
      of sizes of clades in which the same minor, geologically recent innovation has
      arisen multiple times. For three repeated molluscan innovations, 28-71% of
      instantiations are represented by clades of five or fewer species. Such small
      clades would be undetectable in the early history of life. Purportedly unique
      innovations either arose from the union and integration of previously independent
      components or belong to classes of functionally similar innovations. Claims of
      singularity are therefore not well supported by the available evidence. Details
      of initial conditions, evolutionary pathways, phenotypes, and timing are
      contingent, but important ecological, functional, and directional aspects of the
      history of life are replicable and predictable.

PMID- 16443686
TI  - Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer:
      implications for therapy.
AB  - The p53 tumor suppressor retains its wild-type conformation and transcriptional
      activity in half of all human tumors, and its activation may offer a therapeutic
      benefit. However, p53 function could be compromised by defective signaling in the
      p53 pathway. Using a small-molecule MDM2 antagonist, nutlin-3, to probe
      downstream p53 signaling we find that the cell-cycle arrest function of the p53
      pathway is preserved in multiple tumor-derived cell lines expressing wild-type
      p53, but many have a reduced ability to undergo p53-dependent apoptosis. Gene
      array analysis revealed attenuated expression of multiple apoptosis-related
      genes. Cancer cells with mdm2 gene amplification were most sensitive to nutlin-3
      in vitro and in vivo, suggesting that MDM2 overexpression may be the only
      abnormality in the p53 pathway of these cells. Nutlin-3 also showed good efficacy
      against tumors with normal MDM2 expression, suggesting that many of the patients
      with wild-type p53 tumors may benefit from antagonists of the p53-MDM2
      interaction.

PMID- 16443688
TI  - Penetration of intact skin by quantum dots with diverse physicochemical
      properties.
AB  - Skin is the largest organ of the body and is a potential route of exposure to
      engineered nanomaterials, but the permeability of the skin to these nanomaterials
      is unknown. We selected commercially available quantum dots (QD) of two
      core/shell sizes and shapes and three different surface coatings to determine if
      QD could penetrate intact skin in a size- or coating-dependent manner. Spherical
      4.6 nm core/shell diameter QD 565 and ellipsoid 12 nm (major axis) by 6 nm (minor
      axis) core/shell diameter QD 655 with neutral (polyethylene glycol), anionic
      (carboxylic acids) or cationic (polyethylene glycol-amine) coatings were
      topically applied to porcine skin in flow-through diffusion cells at an
      occupationally relevant dose for 8 h and 24 h. Confocal microscopy revealed that
      spherical QD 565 of each surface coating penetrated the stratum corneum and
      localized within the epidermal and dermal layers by 8 h. Similarly, polyethylene
      glycol- and polyethylene glycol-amine-coated ellipsoid QD 655 localized within
      the epidermal layers by 8 h. No penetration of carboxylic acid-coated QD 655 was
      evident until 24 h, at which time localization in the epidermal layers was
      observed. This study showed that quantum dots of different sizes, shapes, and
      surface coatings can penetrate intact skin at an occupationally relevant dose
      within the span of an average-length work day. These results suggest that skin is
      surprisingly permeable to nanomaterials with diverse physicochemical properties
      and may serve as a portal of entry for localized, and possibly systemic, exposure
      of humans to QD and other engineered nanoscale materials.

PMID- 16443687
TI  - In situ labeling of immune cells with iron oxide particles: an approach to detect
      organ rejection by cellular MRI.
AB  - In vivo cell tracking by MRI can provide means to observe biological processes
      and monitor cell therapy directly. Immune cells, e.g., macrophages, play crucial
      roles in many pathophysiological processes, including organ rejection,
      inflammation, autoimmune diseases, cancer, atherosclerotic plaque formation,
      numerous neurological disorders, etc. The current gold standard for diagnosing
      and staging rejection after organ transplantation is biopsy, which is not only
      invasive, but also prone to sampling errors. Here, we report a noninvasive
      approach using MRI to detect graft rejection after solid organ transplantation.
      In addition, we present the feasibility of imaging individual macrophages in vivo
      by MRI in a rodent heterotopic working-heart transplantation model using a more
      sensitive contrast agent, the micrometer-sized paramagnetic iron oxide particle,
      as a methodology to detect acute cardiac rejection.

PMID- 16443689
TI  - Oxidative ability and toxicity of n-hexane insoluble fraction of diesel exhaust
      particles.
AB  - Diesel exhaust particles (DEP) are known to induce adverse biological responses
      such as inflammation of the airway. However, the relationship between the
      chemical characteristics of organic compounds adsorbed on DEP and their
      biological effects is not yet fully understood. In this study, the
      dichloromethane-soluble fraction (DMSF) from DEP was fractionated into its n
      hexane-soluble fraction (n-HSF) and n-hexane-insoluble fraction (n-HISF). Using
      these DEP fractions, we designed the present studies to elucidate (1) chemical
      characteristics, (2) biological characteristics, and (3) the relationship between
      the chemical and the biological characteristics of these DEP fractions.
      Dithiothreitol (DTT) assay, Fourier transform-infrared (FT-IR) spectroscopy,
      proton nuclear magnetic resonance (1H-NMR) spectroscopy, and gas chromatography
      mass spectrometry (GC-MS) were used to characterize their chemical properties.
      Heme oxygenase-1 (HO-1) protein expression, viability of rat alveolar type II
      epithelial cell line (SV40T2), and inflammatory cell infiltration into the
      peritoneal cavity of BALB/c mice were evaluated as markers of oxidative stress,
      cytotoxicity, and inflammatory response, respectively. The oxidative ability of
      the DEP fractions was n-HISF > DMSF > n-HSF. IR, 1H-NMR, and GC-MS spectra showed
      that n-HISF was mainly composed of compounds having many functional groups
      related to oxygenation, such as hydroxyl and carbonyl groups. The relative
      strength of HO-1 protein expression, cytotoxicity, and inflammatory responses was
      also n-HISF > DMSF > n-HSF. All of the n-HISF-induced biological activities were
      decreased by reduction with N-acetyl-L-cysteine (NAC). These results suggest that
      n-HISF has high oxidative ability and many functional groups related to
      oxygenation and that this ability strongly contributes to the induction of
      oxidative stress, cytotoxicity, and inflammatory response.

PMID- 16443690
TI  - Regenerative growth is impacted by TCDD: gene expression analysis reveals
      extracellular matrix modulation.
AB  - Adult zebrafish can completely regenerate their caudal fin following amputation.
      This complex process is initiated by the formation of an epithelial wound cap
      over the amputation site by 12 h post amputation (hpa). Once the cap is formed,
      mesenchymal cells proliferate and migrate from sites distal to the wound plane
      and accumulate under the epithelial cap forming the blastemal structure within 48
      hpa. Blastemal cells proliferate and differentiate, replacing the amputated
      tissues, which are populated with angiogenic vessels and innervating nerves
      during the regenerative outgrowth phase which is completed around 14 days post
      amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed
      zebrafish. To identify the molecular pathways that are perturbed by TCDD
      exposure, male zebrafish were ip injected with 50 ng/g TCDD or vehicle and caudal
      fins were amputated. Regenerating fin tissue was collected at 1, 3, and 5 dpa for
      mRNA abundance analysis. Microarray analysis and quantitative real time PCR
      revealed that wound healing and regeneration alone altered the expression of
      nearly 900 genes by at least two-fold between 1 and 5 dpa. TCDD altered the
      abundance of 370 genes at least two-fold. Among these, several known aryl
      hydrocarbon responsive genes were identified in addition to several genes
      involved in extracellular matrix composition and metabolism. The profile of
      misexpressed genes is suggestive of impaired cellular differentiation and
      extracellular matrix composition potentially regulated by Sox9b.

PMID- 16443691
TI  - Liver deformation in Ahr-null mice: evidence for aberrant hepatic perfusion in
      early development.
AB  - Mice harboring mutations in the Ahr locus display a patent ductus venosus and
      smaller livers throughout life. We tested the hypothesis that these hepatic
      aberrations are secondary to a developmental defect in hepatovascular blood flow
      by performing a detailed analysis of hepatic development in wild-type and Ahr-/-
      mice. This study revealed necrotic lesions in the peripheries of Ahr-/- fetal
      livers as early as embryonic day 15.5, with an increasing incidence up to
      postnatal day 1 and resolution by 2 weeks post partum. To visualize perfusion of
      fetal livers, we injected fluorescein isothiocyanate-labeled dextran into the
      cranial artery and monitored hepatic fluorescence by microscopy. The peripheries
      of the median and left lobes displayed decreased perfusion in regions
      corresponding to those regions that displayed necrosis at later developmental
      times. An examination of adult Ahr-/- animals revealed that smaller livers are
      predominantly due to decreased sizes of the left and right lobes, corresponding
      to regions of decreased perfusion and hepatic necrosis observed in fetal livers.
      Histological aberrations in the portal vein also support a model in which
      perfusion is compromised in the Ahr-/- liver. Taken in sum, these results
      indicate that the Ahr locus is required for normal perfusion of the developing
      liver and that disruption of the AHR signaling pathway gives rise to fetal
      hepatic necrosis and consequent liver deformation which persists through adult
      hood.

PMID- 16443692
TI  - Short- and long-term amiodarone treatments regulate Cav3.2 low-voltage-activated
      T-type Ca2+ channel through distinct mechanisms.
AB  - Low-voltage-activated T-type Ca2+ channels have been recognized recently in the
      mechanisms underlying atrial arrhythmias. However, the pharmacological effects of
      amiodarone on the T-type Ca2+ channel remain unclear. We investigated short- and
      long-term effects of amiodarone on the T-type (Cav 3.2) Ca2+ channel. The Cav3.2
      alpha1H subunit derived from human heart was stably transfected into cells [human
      embryonic kidney (HEK)-Cav3.2] cultured with or without 5 muM amiodarone. Patch
      clamp recordings in the conventional whole-cell configuration were used to
      evaluate the actions of amiodarone on the T-type Ca2+ channel current (ICa.T).
      Amiodarone blockade of ICa.T occurred in a dose- and holding potential-dependent
      manner, shifting the activation and the steady-state inactivation curves in the
      hyperpolarization direction, when amiodarone was applied immediately to the bath
      solution. However, when the HEK-Cav3.2 cells were incubated with 5 microM
      amiodarone for 72 h, ICa.T density was significantly decreased by 31.7+/-2.3% for
      control,-93.1+/-4.3 pA/pF (n=8), versus amiodarone,-56.5+/-3.2 pA/pF (n=13),
      P<0.001. After the prolonged administration of amiodarone, the activation and the
      steady-state inactivation curves were shifted in the depolarization direction by 
      7.1 (n=41) and -5.5 mV (n=37), respectively, and current inactivation was
      significantly delayed [time constant (tau): control, 13.3+/-1.1 ms (n=6) versus
      amiodarone, 39.6+/-5.5 ms (n=6) at -30 mV, P<0.001)]. Nevertheless, short-term
      inhibitory effects of amiodarone on the modified T-type Cav3.2 Ca2+ channel
      created by long-term amiodarone treatment were functionally maintained. We
      conclude that amiodarone exerts its short- and long-term inhibitory actions on
      ICa.T via distinct blocking mechanisms.

PMID- 16443695
TI  - Characterization of low phosphorus insensitive mutants reveals a crosstalk
      between low phosphorus-induced determinate root development and the activation of
      genes involved in the adaptation of Arabidopsis to phosphorus deficiency.
AB  - Low phosphorus (P) availability is one of the most limiting factors for plant
      productivity in many natural and agricultural ecosystems. Plants display a wide
      range of adaptive responses to cope with low P stress, which generally serve to
      enhance P availability in the soil and to increase its uptake by roots. In
      Arabidopsis (Arabidopsis thaliana), primary root growth inhibition and increased
      lateral root formation have been reported to occur in response to P limitation.
      To gain knowledge of the genetic mechanisms that regulate root architectural
      responses to P availability, we designed a screen for identifying Arabidopsis
      mutants that fail to arrest primary root growth when grown under low P
      conditions. Eleven low phosphorus insensitive (lpi) mutants that define at least
      four different complementation groups involved in primary root growth responses
      to P availability were identified. The lpi mutants do not show the typical
      determinate developmental program induced by P stress in the primary root. Other
      root developmental aspects of the low P rescue system, including increased root
      hair elongation and anthocyanin accumulation, remained unaltered in lpi mutants.
      In addition to the insensitivity of primary root growth inhibition, when
      subjected to P deprivation, lpi mutants show a reduced induction in the
      expression of several genes involved in the P starvation rescue system (PHOSPHATE
      TRANSPORTER 1 and 2, PURPLE ACID PHOSPHATASE 1, ACID PHOSPHATASE 5, and INDUCED
      BY PHOSPHATE STARVATION 1). Our results provide genetic support for the role of P
      as an important signal for postembryonic root development and root meristem
      maintenance and show a crosstalk in developmental and biochemical responses to P
      deprivation.

PMID- 16443693
TI  - Cinnamate metabolism in ripening fruit. Characterization of a UDP
      glucose:cinnamate glucosyltransferase from strawberry.
AB  - Strawberry (Fragaria x ananassa) fruit accumulate (hydroxy)cinnamoyl glucose
      (Glc) esters, which may serve as the biogenetic precursors of diverse secondary
      metabolites, such as the flavor constituents methyl cinnamate and ethyl
      cinnamate. Here, we report on the isolation of a cDNA encoding a UDP
      Glc:cinnamate glucosyltransferase (Fragaria x ananassa glucosyltransferase 2
      [FaGT2]) from ripe strawberry cv Elsanta that catalyzes the formation of 1-O-acyl
      Glc esters of cinnamic acid, benzoic acid, and their derivatives in vitro.
      Quantitative real-time PCR analysis indicated that FaGT2 transcripts accumulate
      to high levels during strawberry fruit ripening and to lower levels in flowers.
      The levels in fruits positively correlated with the in planta concentration of
      cinnamoyl, p-coumaroyl, and caffeoyl Glc. In the leaf, high amounts of Glc esters
      were detected, but FaGT2 mRNA was not observed. The expression of FaGT2 is
      negatively regulated by auxin, induced by oxidative stress, and by
      hydroxycinnamic acids. Although FaGT2 glucosylates a number of aromatic acids in
      vitro, quantitative analysis in transgenic lines containing an antisense
      construct of FaGT2 under the control of the constitutive 35S cauliflower mosaic
      virus promoter demonstrated that the enzyme is only involved in the formation of
      cinnamoyl Glc and p-coumaroyl Glc during ripening.

PMID- 16443694
TI  - Phytochrome B represses Teosinte Branched1 expression and induces sorghum
      axillary bud outgrowth in response to light signals.
AB  - Light is one of the environmental signals that regulate the development of shoot
      architecture. Molecular mechanisms regulating shoot branching by light signals
      have not been investigated in detail. Analyses of light signaling mutants
      defective in branching provide insight into the molecular events associated with
      the phenomenon. It is well documented that phytochrome B (phyB) mutant plants
      display constitutive shade avoidance responses, including increased plant height
      and enhanced apical dominance. We investigated the phyB-1 mutant sorghum (Sorghum
      bicolor) and analyzed the expression of the sorghum Teosinte Branched1 gene
      (SbTB1), which encodes a putative transcription factor that suppresses bud
      outgrowth, and the sorghum dormancy-associated gene (SbDRM1), a marker of bud
      dormancy. Buds are formed in the leaf axils of phyB-1; however, they enter into
      dormancy soon after their formation. The dormant state of phyB-1 buds is
      confirmed by the high level of expression of the SbDRM1 gene. The level of SbTB1
      mRNA is higher in the buds of phyB-1 compared to wild type, suggesting that phyB
      mediates the growth of axillary shoots in response to light signals in part by
      regulating the mRNA abundance of SbTB1. These results are confirmed by growing
      wild-type seedlings with supplemental far-red light that induces shade avoidance
      responses. We hypothesize that active phyB (Pfr) suppresses the expression of the
      SbTB1 gene, thereby inducing bud outgrowth, whereas environmental conditions that
      inactivate phyB allow increased expression of SbTB1, thereby suppressing bud
      outgrowth.

PMID- 16443696
TI  - GOLD HULL AND INTERNODE2 encodes a primarily multifunctional cinnamyl-alcohol
      dehydrogenase in rice.
AB  - Lignin content and composition are two important agronomic traits for the
      utilization of agricultural residues. Rice (Oryza sativa) gold hull and internode
      phenotype is a classical morphological marker trait that has long been applied to
      breeding and genetics study. In this study, we have cloned the GOLD HULL AND
      INTERNODE2 (GH2) gene in rice using a map-based cloning approach. The result
      shows that the gh2 mutant is a lignin-deficient mutant, and GH2 encodes a
      cinnamyl-alcohol dehydrogenase (CAD). Consistent with this finding, extracts from
      roots, internodes, hulls, and panicles of the gh2 plants exhibited drastically
      reduced CAD activity and undetectable sinapyl alcohol dehydrogenase activity.
      When expressed in Escherichia coli, purified recombinant GH2 was found to exhibit
      strong catalytic ability toward coniferaldehyde and sinapaldehyde, while the
      mutant protein gh2 completely lost the corresponding CAD and sinapyl alcohol
      dehydrogenase activities. Further phenotypic analysis of the gh2 mutant plants
      revealed that the p-hydroxyphenyl, guaiacyl, and sinapyl monomers were reduced in
      almost the same ratio compared to the wild type. Our results suggest GH2 acts as
      a primarily multifunctional CAD to synthesize coniferyl and sinapyl alcohol
      precursors in rice lignin biosynthesis.

PMID- 16443697
TI  - Effects of feeding Spodoptera littoralis on lima bean leaves. III. Membrane
      depolarization and involvement of hydrogen peroxide.
AB  - In response to herbivore (Spodoptera littoralis) attack, lima bean (Phaseolus
      lunatus) leaves produced hydrogen peroxide (H(2)O(2)) in concentrations that were
      higher when compared to mechanically damaged (MD) leaves. Cellular and
      subcellular localization analyses revealed that H(2)O(2) was mainly localized in
      MD and herbivore-wounded (HW) zones and spread throughout the veins and tissues.
      Preferentially, H(2)O(2) was found in cell walls of spongy and mesophyll cells
      facing intercellular spaces, even though confocal laser scanning microscopy
      analyses also revealed the presence of H(2)O(2) in mitochondria/peroxisomes.
      Increased gene and enzyme activations of superoxide dismutase after HW were in
      agreement with confocal laser scanning microscopy data. After MD, additional
      application of H(2)O(2) prompted a transient transmembrane potential (V(m))
      depolarization, with a V(m) depolarization rate that was higher when compared to
      HW leaves. In transgenic soybean (Glycine max) suspension cells expressing the
      Ca(2+)-sensing aequorin system, increasing amounts of added H(2)O(2) correlated
      with a higher cytosolic calcium ([Ca(2+)](cyt)) concentration. In MD and HW
      leaves, H(2)O(2) also triggered the increase of [Ca(2+)](cyt), but MD-elicited
      [Ca(2+)](cyt) increase was more pronounced when compared to HW leaves after
      addition of exogenous H(2)O(2). The results clearly indicate that V(m)
      depolarization caused by HW makes the membrane potential more positive and
      reduces the ability of lima bean leaves to react to signaling molecules.

PMID- 16443699
TI  - Function and characterization of starch synthase I using mutants in rice.
AB  - Four starch synthase I (SSI)-deficient rice (Oryza sativa) mutant lines were
      generated using retrotransposon Tos17 insertion. The mutants exhibited different
      levels of SSI activities and produced significantly lower amounts of SSI protein
      ranging from 0% to 20% of the wild type. The mutant endosperm amylopectin showed
      a decrease in chains with degree of polymerization (DP) 8 to 12 and an increase
      in chains with DP 6 to 7 and DP 16 to 19. The degree of change in amylopectin
      chain-length distribution was positively correlated with the extent of decrease
      in SSI activity in the mutants. The structural changes in the amylopectin
      increased the gelatinization temperature of endosperm starch. Chain-length
      analysis of amylopectin in the SSI band excised from native-polyacrylamide gel
      electrophoresis/SS activity staining gel showed that SSI preferentially
      synthesized DP 7 to 11 chains by elongating DP 4 to 7 short chains of glycogen or
      amylopectin. These results show that SSI distinctly generates DP 8 to 12 chains
      from short DP 6 to 7 chains emerging from the branch point in the A or B(1) chain
      of amylopectin. SSI seemingly functions from the very early through the late
      stage of endosperm development. Yet, the complete absence of SSI, despite being a
      major SS isozyme in the developing endosperm, had no effect on the size and shape
      of seeds and starch granules and the crystallinity of endosperm starch,
      suggesting that other SS enzymes are probably capable of partly compensating SSI
      function. In summary, this study strongly suggested that amylopectin chains are
      synthesized by the coordinated actions of SSI, SSIIa, and SSIIIa isoforms.

PMID- 16443700
TI  - Early empirical glycopeptide therapy for patients with methicillin-resistant
      Staphylococcus aureus bacteraemia: impact on the outcome.
AB  - OBJECTIVES: To evaluate whether appropriate early empirical glycopeptide therapy
      improves outcomes of patients with methicillin-resistant Staphylococcus aureus
      (MRSA) bacteraemia. METHODS: We retrospectively collected the data for all adult
      patients with confirmed MRSA bacteraemia diagnosed and treated at National Taiwan
      University Hospital during the period 1 April 1997-31 March 2001, and followed
      their survival up to three years. The main outcome measures were MRSA-related
      death and all-cause mortality. RESULTS: There were 77 MRSA-related deaths among
      162 patients. There was no statistically significant difference in MRSA-related
      deaths between patients receiving glycopeptides before or within 48 h after blood
      culture (n = 43) (55%, 18/33, non-septic shock group; 90%, 9/10, septic shock
      group) or those whose glycopeptide therapy was begun more than 48 h after blood
      culture (n = 119) (37%, 40/107, non-septic shock group; 83%, 10/12, septic shock
      group) (P = 0.11 and 1.00, respectively). The outcome measure of all-cause
      mortality from 30 days to 3 years yields similar results. Multivariate logistic
      regression analysis and Cox analysis showed that the length of delay (daily
      increment) between blood culture sampling and start of glycopeptide therapy did
      not have a statistically significant impact on MRSA-related death or all-cause 30
      day mortality after adjusting for the effect of other variables [adjusted odds
      ratio 0.99, 95% confidence interval (95% CI) 0.88-1.12; adjusted hazard ratio
      0.87, 95% CI 0.74-1.02, respectively). CONCLUSIONS: The hypothesis that earlier
      empirical use of glycopeptide therapy reduces mortality in patients with hospital
      acquired MRSA bacteraemia was not supported.

PMID- 16443698
TI  - A role for mitochondria in the establishment and maintenance of the maize root
      quiescent center.
AB  - Mitochondria in the oxidizing environment of the maize (Zea mays) root quiescent
      center (QC) are altered in function, but otherwise structurally normal. Compared
      to mitochondria in the adjacent, rapidly dividing cells of the proximal root
      tissues, mitochondria in the QC show marked reductions in the activities of
      tricarboxylic acid cycle enzymes. Pyruvate dehydrogenase activity was not
      detected in the QC. Use of several mitochondrial membrane potential (DeltaPsi(m))
      sensing probes indicated a depolarization of the mitochondrial membrane in the
      QC, which suggests a reduction in the capacity of QC mitochondria to generate ATP
      and NADH. We postulate that modifications of mitochondrial function are central
      to the establishment and maintenance of the QC.

PMID- 16443701
TI  - Inhaled corticosteroids moderate lung function decline in adults with asthma.

PMID- 16443702
TI  - Exercise induced bronchoconstriction in elite athletes: measuring the fall.

PMID- 16443703
TI  - Why does airway inflammation persist after the smoking stops?

PMID- 16443704
TI  - Is EGFR expression important in non-small cell lung cancer?

PMID- 16443705
TI  - Inhaled corticosteroids and decline of lung function in community residents with
      asthma.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) constitute the cornerstone of treatment
      for asthma. Many studies have reported beneficial short term effects of these
      drugs, but there are few data on the long term effects of ICS on the decline in
      forced expiratory volume in 1 second (FEV(1)). This study was undertaken to
      determine whether adults with asthma treated with ICS have a less pronounced
      decline in FEV(1) than those not treated with ICS. METHODS: Two hundred and
      thirty four asthmatic individuals from a longitudinal epidemiological study of
      the general population of Copenhagen, Denmark were divided into two groups; 44
      were treated with ICS and 190 were not treated with ICS. The annual decline in
      FEV(1) was measured over a 10 year follow up period. RESULTS: The decline in
      FEV(1) in the 44 patients receiving ICS was 25 ml/year compared with 51 ml/year
      in the 190 patients not receiving this treatment (p<0.001). The linear regression
      model with ICS as the variable of interest and sex, smoking, and wheezing as
      covariates showed that treatment with ICS was associated with a less steep
      decline in FEV(1) of 18 ml/year (p = 0.01). Adjustment for additional variables
      including age, socioeconomic status, body mass index, mucus hypersecretion, and
      use of other asthma medications did not change these results. CONCLUSIONS:
      Treatment with ICS is associated with a significantly reduced decline in
      ventilatory function.

PMID- 16443706
TI  - Addition of salmeterol to existing treatment in patients with COPD: a 12 month
      study.
AB  - BACKGROUND: This study investigated the addition of salmeterol to existing
      treatment for exacerbations in patients with poorly reversible chronic
      obstructive pulmonary disease (COPD). METHODS: 634 patients aged >40 years with a
      history of COPD exacerbations (including at least two in the previous year) and
      poor reversibility of airflow obstruction (< or =10% predicted forced expiratory
      volume in 1 second) received either salmeterol 50 mug or placebo twice daily from
      a Diskus inhaler for 12 months. The primary outcome was the number of moderate
      and severe exacerbations. RESULTS: The median rate of moderate or severe
      exacerbations in the intent-to-treat (ITT) population was lower in the salmeterol
      group (0.00, range 0.0-9.8, n = 316) than in the placebo group (0.93, range 0.0
      13.0, n = 318), but the difference was not statistically significant (p = 0.27).
      The median rate of exacerbations in the per protocol population (>90% compliance)
      was also found to be lower in the salmeterol group (0.00, range 0.0-5.0, n = 206)
      than in the placebo group (0.93, range 0.0-5.6, n = 195) and did reach
      statistical significance (p = 0.007). For secondary end points, patients
      receiving salmeterol had significant improvement in lung hyperinflation measured
      by inspiratory capacity which was evident at 4 weeks and maintained over 12
      months (p = 0.035), and a significant improvement in health status measured by
      the St George's Respiratory Questionnaire at 12 months (p = 0.002). CONCLUSION:
      Salmeterol has a positive effect on symptoms and health status of patients with
      COPD when added to usual treatment. Exacerbations are only reduced in patients
      who comply with treatment.

PMID- 16443707
TI  - COPD exacerbations .1: Epidemiology.
AB  - The epidemiology of exacerbations of chronic obstructive pulmonary disease (COPD)
      is reviewed with particular reference to the definition, frequency, time course,
      natural history and seasonality, and their relationship with decline in lung
      function, disease severity and mortality. The importance of distinguishing
      between recurrent and relapsed exacerbations is discussed.

PMID- 16443708
TI  - Asthma exacerbations during pregnancy: incidence and association with adverse
      pregnancy outcomes.
AB  - Exacerbations of asthma during pregnancy represent a significant clinical problem
      and may be related to poor pregnancy outcomes. A systematic review of the
      literature was conducted for publications related to exacerbations during
      pregnancy. Four studies with a control group (no asthma) and two groups of women
      with asthma (exacerbation, no exacerbation) were included in meta-analyses using
      fixed effects models. During pregnancy, exacerbations of asthma which require
      medical intervention occur in about 20% of women, with approximately 6% of women
      being admitted to hospital. Exacerbations during pregnancy occur primarily in the
      late second trimester; the major triggers are viral infection and non-adherence
      to inhaled corticosteroid medication. Women who have a severe exacerbation during
      pregnancy are at a significantly increased risk of having a low birth weight baby
      compared with women without asthma. No significant associations between
      exacerbations during pregnancy and preterm delivery or pre-eclampsia were
      identified. Inhaled corticosteroid use may reduce the risk of exacerbations
      during pregnancy. Pregnant women may be less likely to receive oral steroids for
      the emergency management of asthma. The effective management and prevention of
      asthma exacerbations during pregnancy is important for the health of both the
      mother and fetus.

PMID- 16443709
TI  - Late pulmonary artery stump thrombosis with post embolic pulmonary hypertension
      after pneumonectomy.
AB  - Ten years after right pneumonectomy for primary lung cancer, a 51 year old man
      developed a pulmonary artery stump thrombosis which produced microemboli in the
      remaining lung and, in turn, led to chronic pulmonary hypertension. This case
      strongly suggests that prolonged postoperative thromboembolic prophylaxis should
      be considered in patients undergoing right pneumonectomy.

PMID- 16443710
TI  - Increasing paediatric empyema admissions.

PMID- 16443711
TI  - Clinical importance of the Step 3 choice in asthma.

PMID- 16443712
TI  - Repeated tuberculin testing does not induce false positive ELISPOT results.

PMID- 16443714
TI  - An unusual cause of superior vena cava obstruction.

PMID- 16443715
TI  - Measuring impulsivity in adolescents with serious substance and conduct problems.
AB  - Adolescents with substance use and conduct disorders have high rates of
      aggression and attention deficit hyperactivity disorder (ADHD), all of which have
      been characterized in part by impulsivity. Developing measures that capture
      impulsivity behaviorally and correlate with self-reported impulsivity has been
      difficult. One promising behavioral measure, however, is a variant of the
      continuous performance test, the Immediate Memory Test/Delayed Memory Test
      (IMT/DMT). The authors showed significant group differences between adolescents
      in treatment for serious substance and conduct problems and community controls on
      impulsivity measures, both behavioral and self-report, as well as on aggression
      and problem behavior measures. Furthermore, the IMT/DMT correlated significantly
      with self-reported impulsivity. In summary, the IMT/DMT may be an effective
      behavioral measure of impulsivity in adolescents.

PMID- 16443716
TI  - Psychometric properties of the Dominic interactive assessment: a computerized
      self-report for children.
AB  - The reliability and validity of the Dominic Interactive (DI) assessment were
      evaluated. The DI is a computerized self-report measure for children, which
      assesses symptom presence for seven DSM-IV diagnoses. The participants were 322
      children (169 cocaine exposed, 153 non-cocaine exposed) who were recruited at
      birth for a prospective longitudinal study. At 6 years of age, measures of self
      report, parent report, and observational data were collected. Moderate to
      excellent internal consistencies on the DI were found for the total sample as
      well as for subsamples based on cocaine status and gender. Concurrent validity
      correlations between DI scales and the Child Behavior Checklist, Affect in Play
      Scale, a modified Conners's Teachers Rating Scale, and the Parenting Stress Index
      were examined. Significant relationships among scales were more apt to be among
      comparisons that assessed externalizing behaviors. Overall, low correlations were
      obtained, which are comparable to other studies that evaluate agreement between
      child and parent report of behaviors.

PMID- 16443717
TI  - Using self-report assessment methods to explore facets of mindfulness.
AB  - The authors examine the facet structure of mindfulness using five recently
      developed mindfulness questionnaires. Two large samples of undergraduate students
      completed mindfulness questionnaires and measures of other constructs.
      Psychometric properties of the mindfulness questionnaires were examined,
      including internal consistency and convergent and discriminant relationships with
      other variables. Factor analyses of the combined pool of items from the
      mindfulness questionnaires suggested that collectively they contain five clear,
      interpretable facets of mindfulness. Hierarchical confirmatory factor analyses
      suggested that at least four of the identified factors are components of an
      overall mindfulness construct and that the factor structure of mindfulness may
      vary with meditation experience. Mindfulness facets were shown to be
      differentially correlated in expected ways with several other constructs and to
      have incremental validity in the prediction of psychological symptoms. Findings
      suggest that conceptualizing mindfulness as a multifaceted construct is helpful
      in understanding its components and its relationships with other variables.

PMID- 16443718
TI  - California verbal learning test indicators of Malingered Neurocognitive
      Dysfunction: sensitivity and specificity in traumatic brain injury.
AB  - The present study used well-defined traumatic brain injury (TBI) and mixed
      neurological (other than TBI) and psychiatric samples to examine the specificity
      and sensitivity to Malingered Neurocognitive Dysfunction (MND) of four individual
      California Verbal Learning Test (CVLT) variables and eight composite CVLT
      malingering indicators. Participants were 275 traumatic brain injury and 352
      general clinical patients seen for neuropsychological evaluation. The TBI
      patients were assigned to one of five groups using the Slick, Sherman, and
      Iverson (1999) criteria: no incentive, incentive only, suspect, and malingering
      (both Probable MND and Definite MND). Within TBI, persons with the strongest
      evidence for malingering (Probable and Definite) had the most extreme scores.
      Good sensitivity (approximately 50%) in the context of excellent specificity (>
      95%) was found in the TBI samples. Issues related to the appropriate clinical
      application of these data are discussed.

PMID- 16443719
TI  - The Stroop color-word test: influence of age, sex, and education; and normative
      data for a large sample across the adult age range.
AB  - The Stroop Color-Word Test was administered to 1,856 cognitively screened,
      healthy Dutch speaking participants aged 24 to 81 years. The effects of age,
      gender, and education on Stroop test performance were investigated to adequately
      stratify the normative data. The results showed that especially the speed
      dependent Stroop scores (time to complete a subtest), rather than the accuracy
      measures (the errors made per Stroop sub-task), were profoundly affected by the
      demographic variables. In addition to the main effects of the demographic
      variables, an Age Low Level of Education interaction was found for the Error III
      and the Stroop Interference scores. This suggests that executive function, as
      measured by the Stroop test, declines with age and that the decline is more
      pronounced in people with a low level of education. This is consistent with the
      reserve hypothesis of brain aging (i.e., that education generates reserve
      capacity against the damaging effects of aging on brain functions). Normative
      Stroop data were established using both a regression-based and traditional
      approach, and the appropriateness of both methods for generating normative data
      is discussed.

PMID- 16443720
TI  - External correlates of the MMPI-2 content component scales in mental health
      inpatients.
AB  - External correlates of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2)
      Content Component Scales were identified using an inpatient sample of 544 adults.
      The Brief Psychiatric Rating Scale (BPRS) and Symptom Checklist 90-Revised (SCL
      90-R) produced correlates of the Content Component Scales, demonstrating external
      validity with clinician-rated and self-report scales. Relationships between MMPI
      2 Content Component Scales and patient hospital chart variables were also
      examined. Results demonstrated cross-criterion validity in that most MMPI-2
      Content Component Scales correlated with appropriate BPRS dimensions, SCL-90-R
      items, and other patient variables. Discriminant validity of the Content
      Component Scales was also demonstrated. In addition, the finding that similar
      patterns of correlates are produced when the component scales are correlated with
      a self-report measure, as well as clinician ratings and medical chart variables,
      provides converging lines of evidence supporting the construct validity of the
      Content Component Scales.

PMID- 16443721
TI  - An evaluation of the MMPI-2 and MMPI-a true response inconsistency (TRIN) scales.
AB  - The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) and Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2) True Response Inconsistency (TRIN)
      scales are measures of acquiescence and non-acquiescence included among the
      standard validity scales on these instruments. The goals of this study were to
      evaluate the effectiveness of these scales in detecting varying degrees of
      acquiescence and non-acquiescence and to evaluate cutoff scores for clinical use.
      After the removal of invalid protocols from the MMPI-2 and MMPI-A normative
      samples, each normative sample was randomly divided in half. For each measure,
      one half of the normative sample served as a comparison group and the other half
      was modified with increasing degrees (10%, 20%, 30%, 40%, and 50%) of randomly
      inserted true or false responses. The results for a 9.1% base rate of
      acquiescence or non-acquiescence provide support for TRIN cutoff scores at or
      near those presented in the MMPI-A and MMPI-2 manuals.

PMID- 16443722
TI  - Internal consistency reliability of the self-report antisocial process screening
      device.
AB  - The self-report version of the Antisocial Process Screening Device (APSD) has
      become a popular measure for assessing psychopathic features in justice-involved
      adolescents. However, the internal consistency reliability of its component
      scales (Narcissism, Callous-Unemotional, and Impulsivity) has been questioned in
      several studies. This study evaluates the internal consistency reliability of the
      self-report APSD by examining various indices (e.g., Cronbach's alpha, mean
      interitem correlation) across 11 studies. Whereas the Narcissism and Impulsivity
      scales display moderate to good reliability, internal consistency indices for the
      Callous-Unemotional scale are consistently poor across studies. Suggestions are
      made for revisions to this scale that would substantially improve its internal
      consistency reliability.

PMID- 16443723
TI  - In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid
      using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4
      (2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) in
      the rat.
AB  - Plaques in the parenchyma of the brain containing Abeta peptides are one of the
      hallmarks of Alzheimer's disease. These Abeta peptides are produced by the final
      proteolytic cleavage of the amyloid precursor protein by the intramembraneous
      aspartyl protease gamma-secretase. Thus, one approach to lowering levels of Abeta
      has been via the inhibition of the gamma-secretase enzyme. Here, we report a
      novel, bioavailable gamma-secretase inhibitor, N-[cis-4-[(4
      chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1
      trifluoromethanesulfonamide (MRK-560) that displayed oral pharmacokinetics
      suitable for once-a-day dosing. It was able to markedly reduce Abeta in the brain
      and cerebrospinal fluid (CSF) in the rat, with ED(50) values of 6 and 10 mg/kg,
      respectively. Time-course experiments using MRK-560 demonstrated these reductions
      in Abeta could be maintained for 24 h, and comparable temporal reductions in rat
      brain and CSF Abeta(40) further suggested that these two pools of Abeta are
      related. This relationship between the brain and CSF Abeta was maintained when
      MRK-560 was dosed once a day for 2 weeks, and accordingly, when all the data for
      the dose-response curve and time courses were correlated, a strong association
      was observed between the brain and CSF Abeta levels. These results demonstrate
      that MRK-560 is an orally bioavailable gamma-secretase inhibitor with the ability
      to markedly reduce Abeta peptide in the brain and CSF of the rat and confirm the
      utility of the rat for assessing the effects of gamma-secretase inhibitors on
      central nervous system Abeta(40) levels in vivo.

PMID- 16443724
TI  - Best practice in primary care pathology: review 2.
AB  - This second best practice review examines five series of common primary care
      questions in laboratory medicine: (1) laboratory testing for allergy, (2)
      diagnosis and monitoring of menopause, (3) the use of urine cytology, (4) the
      usefulness of the erythrocyte sedimentation rate, and (5) the investigation of
      possible urinary tract infection. The review is presented in a question-answer
      format. The recommendations represent a precis of guidance found using a
      standardised literature search of national and international guidance notes,
      consensus statements, health policy documents, and evidence based medicine
      reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary
      research documents. They are standards but form a guide to be set in the clinical
      context. Most are consensus rather than evidence based. They will be updated
      periodically to take account of new information.

PMID- 16443725
TI  - An approach to endomyocardial biopsy interpretation.
AB  - The endomyocardial biopsy (EMB) remains the gold standard mode of investigation
      for diagnosing many primary and secondary cardiac conditions. Through a
      percutaneous and transvenous route, tissue fragments are generally procured from
      the right ventricular septum, with very few complications. Widespread use of EMB
      followed the development of heart transplantation as a means to follow allograft
      rejection. It has since been useful in helping to diagnose conditions affecting
      the heart, including cardiomyopathies, myocarditis, infiltrative lesions,
      arrhythmias, and drug toxicities. The procedure has also been used as a research
      tool to investigate the natural history of disease and the cardiotoxicity of new
      medications. This review presents an approach to the evaluation of the EMB, which
      is particularly directed towards those who may be asked to interpret such
      biopsies, but are not dedicated cardiovascular pathologists. Through a systematic
      evaluation of the endocardium, myocardium, interstitium, and intramural vessels,
      in the context of a complete clinical history, enough information can be deduced
      to diagnose or exclude specific conditions of clinical value.

PMID- 16443726
TI  - The NHS breast screening programme (pathology) EQA: experience in recent years
      relating to issues involved in individual performance appraisal.
AB  - BACKGROUND: The original role of the National Health Service breast screening
      programme (pathology) external quality assessment (EQA) scheme was educational;
      it aimed to raise standards, reinforce use of common terminology, and assess the
      consistency of pathology reporting of breast disease in the UK. AIMS/METHODS: To
      examine the performance (scores) of pathologists participating in the scheme in
      recent years. The scheme has evolved to help identify poor performers, reliant
      upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint
      strategies were evaluated and implications discussed. RESULTS/CONCLUSIONS:
      Pathologists who joined the scheme improved over time, particularly those who did
      less well initially. There was no obvious association between performance and the
      number of breast cancer cases reported each year. This is not unexpected because
      the EQA does not measure expertise, but was established to demonstrate a common
      level of performance (conformity to consensus) for routine cases, rather than the
      ability to diagnose unusual/difficult cases. A new method of establishing
      cutpoints using interquartile ranges is proposed. The findings also suggest that
      EQA can alter a pathologist's practice: those who leave the scheme (for whatever
      reason) have, on average, marginally lower scores. Consequently, with the
      cutpoint methodology currently used (which is common to several EQA schemes)
      there is the potential for the cutpoint to drift upwards. In future, individuals
      previously deemed competent could subsequently be erroneously labelled as poor
      performers. Due consideration should be given to this issue with future
      development of schemes.

PMID- 16443727
TI  - Impact of a national external quality assessment scheme for breast pathology in
      the UK.
AB  - BACKGROUND: This article presents the results and observed effects of the UK
      National Health Service Breast Screening Programme (NHSBSP) external quality
      assurance scheme in breast histopathology. AIMS/METHODS: The major objectives
      were to monitor and improve the consistency of diagnoses made by pathologists and
      the quality of prognostic information in pathology reports. The scheme is based
      on a twice yearly circulation of 12 cases to over 600 registered participants.
      The level of agreement was generally measured using kappa statistics. RESULTS:
      Four main situations were encountered with respect to diagnostic consistency,
      namely: (1) where consistency is naturally very high-this included diagnosing in
      situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated
      benign lesions; (2) where the level of consistency was low but could be improved
      by making guidelines more detailed and explicit-this included histological
      grading; (3) where consistency could be improved but only by changing the system
      of classification-this included classification of ductal carcinoma in situ; and
      (4) where no improvement in consistency could be achieved-this included
      diagnosing atypical hyperplasia and reporting vascular invasion. Size
      measurements were more consistent for invasive than in situ carcinomas. Even in
      cases where there is a high level of agreement on tumour size, a few widely
      outlying measurements were encountered, for which no explanation is readily
      forthcoming. CONCLUSIONS: These results broadly confirm the robustness of the
      systems of breast disease diagnosis and classification adopted by the NHSBSP, and
      also identify areas where improvement or new approaches are required.

PMID- 16443728
TI  - Platelet volume indices in patients with coronary artery disease and acute
      myocardial infarction: an Indian scenario.
AB  - AIMS: To study platelet volume indices (PVI) in the spectrum of ischaemic heart
      diseases. METHODS: A total of 210 cases were studied; 94 patients had unstable
      angina (UA) or acute myocardial infarction (AMI) diagnosed on the basis of
      history, characteristic electrocardiographic changes, and increased cardiac
      enzyme activities. Seventy patients had stable coronary artery disease (stable
      CAD) or were admitted for a coronary angiography or coronary artery bypass graft
      procedure. The third group comprised 30 age and sex matched healthy controls with
      no history of heart disease and a normal electrocardiogram. RESULTS: All PVI-mean
      platelet volume (MPV), platelet distribution width (PDW), and platelet large cell
      ratio (P-LCR)-were significantly raised in patients with AMI and UA (mean MPV,
      10.43 (SD, 1.03) fL; mean PDW, 13.19 (SD, 2.34) fL; mean P-LCR, 29.4% (SD,
      7.38%)) compared with those with stable CAD (mean MPV, 9.37 (SD, 0.99) fL; mean
      PDW, 11.35 (SD, 1.95) fL; mean P-LCR, 22.55% (SD, 6.65%)) and the control group
      (mean MPV, 9.2 (SD, 0.91) fL; mean PDW, 10.75 (SD, l.42) fL; mean P-LCR, 20.65%
      (SD, 6.14%)). CONCLUSIONS: Larger platelets are haemostatically more active and
      are a risk factor for developing coronary thrombosis, leading to myocardial
      infarction. Patients with larger platelets can easily be identified during
      routine haematological analysis and could possibly benefit from preventive
      treatment. Thus, PVI are an important, simple, effortless, and cost effective
      tool that should be used and explored extensively, especially in countries such
      as India, for predicting the possibility of impending acute events.

PMID- 16443729
TI  - Prognostic value of stage IV neuroblastoma metastatic immunophenotype in the bone
      marrow: preliminary report.
AB  - AIM: To correlate the immunophenotype of metastatic cells in the bone marrow of
      patients with neuroblastoma with early treatment failure. METHODS: The studies
      were performed on bone marrow material obtained from children treated in the
      department of paediatric oncology, haematology, and transplantology, Poznan
      University of Medical Sciences, Poland from 1996 to 2003. Immunocytochemical
      analysis of nervous tissue markers (using the immunomax technique) was performed
      on 108 bone marrow preparations obtained from 36 children diagnosed with
      neuroblastoma (stage IV with bone marrow metastases). The analysis included
      expression of PGP 9.5 protein, substance P, chromogranin A, bombesin, galanin,
      neuropeptide Y (NPY), and vasoactive intestinal peptide in neuroblastoma
      metastatic cells defined by the expression of neurone specific enolase. RESULTS:
      Nineteen relapses occurred within 12 months of the end of treatment. Correlation
      between the various markers studied and early treatment failure, using Fisher's
      exact test, revealed that chromogranin A and NPY are strong indicators of an
      unfavourable prognosis in patients with stage IV neuroblastoma (p < 0.001 and p <
      0.0002, respectively). CONCLUSION: Determination of metastatic cell
      immunophenotypes in bone marrow (particularly chromogranin A and NPY) may help
      establish the short term prognosis in children with neuroblastoma.

PMID- 16443730
TI  - Twenty year review of histopathological findings in enucleated/eviscerated eyes.
AB  - BACKGROUND/AIMS: To evaluate the need for routine histopathological analysis of
      enucleated/eviscerated eyes and changes in indications for eye removal. METHODS:
      Retrospective review of all enucleation/evisceration histopathology reports over
      20 years. Clinical history was correlated with pathological findings. Two 10 year
      periods (1984-93, 1994-2003) were compared to detect changes in indications for
      eye removal. RESULTS: In total, 285 histopathology results were traced from 1984
      to 2003; 161 and 124 were evisceration and enucleation specimens, respectively.
      Glaucoma, malignant melanoma, trauma, and retinal detachment were the most
      frequent diagnoses 1984-1993. Ocular trauma was the most frequent diagnosis 1994
      2003, followed by phthisis bulbi and endophthalmitis. Three cases were diagnosed
      as metastatic carcinoma; all were suspected preoperatively. A fourth case was a
      diagnostic surprise: adenocarcinoma found in an eye removed for pain and
      phthisis. Comparison of two 10 year periods showed a decrease in the number of
      enucleations/eviscerations, perhaps reflecting a decrease in the number of
      specimens sent. A preference for eviscerations was evident over the 20 years.
      CONCLUSION: The number of eyes removed and histologically analysed decreased in
      the period 1994 to 2003, perhaps because of better treatment options, allowing
      globe preservation. There was a significant shift in the diagnosis in the two
      time periods, and a preference for evisceration in both. Only one diagnostic
      surprise was discovered (0.35%). This study does not support the need to send all
      globes/contents for histopathological examination. However, because of the one
      unexpected finding, it is recommended where the examination is incomplete or the
      history of visual loss is unclear.

PMID- 16443731
TI  - An audit of thrombophilia screens: results from the National Pathology Alliance
      benchmarking review.
AB  - AIMS: The National Pathology Alliance benchmarking review has completed six years
      of data collection and analysis of the workload and organisation of haematology
      laboratories in the UK. This study audits national practice of routine
      thrombophilia screening against the current standards, as set out in the British
      committee for standards in haematology (BCSH) guidelines on investigation of
      heritable thrombophilia. METHODS: Each laboratory completed a standard data
      collection questionnaire about the number of routine thrombophilia assays
      performed each year. Information was collected on which thrombophilia tests were
      performed as part of a routine thrombophilia screen. These results were then
      compared against the BCSH guidelines on investigation of heritable thrombophilia.
      RESULTS: Of the 57 National Health Service trusts that submitted data for review
      in 2002/2003, 47 performed a routine thrombophilia screen. Ten laboratories
      complied with the guidelines but 37 laboratories did not. CONCLUSION: There was
      variation in practice in the tests used in routine thrombophilia screens. There
      is evidence that some laboratories deviate from what may be regarded as "evidence
      based practice". The lack of compliance with the guidelines was in general
      associated with the performance of additional tests not recommended in the
      guideline. In a minority of laboratories, a clinically significant diagnosis
      would be missed by the failure to include one or more tests in a thrombophilia
      screen.

PMID- 16443732
TI  - cDNA microarray analysis of cancer associated gene expression profiles in
      malignant peripheral nerve sheath tumours.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumour (MPNST) is a highly
      aggressive malignancy that arises within peripheral nerves, and is associated
      with poor prognosis. Little is known about the underlying biology of MPNST,
      especially the mechanisms involved in cell proliferation, invasion, or escape
      from apoptosis. AIMS: To identify genes differentially expressed in MPNST
      compared with benign tumours, such as neurofibromas and schwannomas, by means of
      cDNA microarray analysis. METHODS: Six MPNST cases and five benign cases (three
      schwannomas and two neurofibromas) were analysed. RESULTS: Six genes (keratin 18,
      survivin, tenascin C, adenosine deaminase, collagen type VIa3, and collagen type
      VIIa1) were significantly upregulated in MPNST, whereas one gene, insulin-like
      growth factor binding protein 6, was downregulated in MPNST. Survivin and
      tenascin C expression was validated by reverse transcription polymerase chain
      reaction. Immunohistochemistry confirmed upregulation of survivin in MPNST at the
      protein level in six of eight cases compared with benign tumours. Tenascin C was
      also expressed at the invasive front and tumorous stroma in all MPNST cases.
      MPNST cells expressed tenascin C in four of nine cases. CONCLUSIONS: Survivin and
      tenascin C may be associated with the malignant potential of MPNST and could be
      considered as potential therapeutic targets.

PMID- 16443733
TI  - Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in
      cutaneous melanoma: a case-control study.
AB  - BACKGROUND: Cutaneous melanoma spreads preferentially through the lymphatic route
      and sentinel lymph node (SLN) status is regarded as the most important predictor
      of survival. AIMS: To evaluate whether tumour lymphangiogenesis and the
      expression of vascular endothelial growth factor C (VEGF-C) is related to the
      risk of SLN metastasis and to clinical outcome in a case-control series of
      patients with melanoma. METHODS: Forty five invasive melanoma specimens (15 cases
      and 30 matched controls) were investigated by immunostaining for the lymphatic
      endothelial marker D2-40 and for VEGF-C. Lymphangiogenesis was measured using
      computer assisted morphometric analysis. RESULTS: Peritumorous lymphatic vessels
      were more numerous, had larger average size, and greater relative area than
      intratumorous lymphatics. The number and area of peritumorous and intratumorous
      lymphatics was significantly higher in melanomas associated with SLN metastasis
      than in non-metastatic melanomas. No significant difference in VEGF-C expression
      by neoplastic cells was shown between metastatic and non-metastatic melanomas.
      Using logistic regression analysis, intratumorous lymphatic vessel (LV) area was
      the most significant predictor of SLN metastasis (p = 0.04). Using multivariate
      analysis, peritumorous LV density was an independent variable affecting overall
      survival, whereas the intratumorous LV area approached significance (p = 0.07).
      CONCLUSIONS: This study provides evidence that the presence of high peritumorous
      and intratumorous lymphatic microvessel density is associated with SLN metastasis
      and shorter survival. The intratumorous lymphatic vessel area is the most
      significant factor predicting SLN metastasis. The tumour associated lymphatic
      network constitutes a potential criterion in the selection of high risk patients
      for complementary treatment and a new target for antimelanoma therapeutic
      strategies.

PMID- 16443734
TI  - Immunohistochemical assessment of hepatitis C virus antigen in cholestatic
      hepatitis after liver transplantation.
AB  - BACKGROUND: Patients with common variable immunodeficiency may exhibit rapidly
      progressive hepatitis when infected with hepatitis C virus (HCV), leading to
      cirrhosis and liver failure. Liver transplantation in these patients may result
      in a cholestatic form of HCV reinfection with exceptionally high virus loads.
      AIMS: To report an immunohistochemical investigation of the pretransplant and
      post-transplant liver of one such patient. METHODS/RESULTS: On
      immunohistochemical staining of frozen sections with anti-HCV core monoclonal
      antibody or fluorescein labelled human polyclonal anti-HCV IgG, no HCV antigens
      were demonstrated in the native cirrhotic liver removed at transplant, despite a
      viral load of 10(6.4) genomes/g. The transplanted liver, collected six weeks post
      transplant, exhibited cholestatic recurrent hepatitis, had an HCV virus load of
      10(10) genomes/g of liver, and revealed HCV antigen in the cytoplasm of most
      hepatocytes, with a pronounced periportal distribution. No virus antigen was
      demonstrable in other cell types. The core antigen was also detected in paraffin
      wax embedded, formaldehyde fixed tissue of this liver after high temperature
      antigen retrieval, but not in the native cirrhotic liver or a selection of HCV
      positive livers collected pretransplant from immunocompetent patients. Attempts
      to delineate the distribution of E1, NS3, and NS4 antigens were unsuccessful
      because monoclonal antibodies to these antigens produced "false positive"
      staining of foci of hepatocytes in the post-transplant livers of HCV seronegative
      patients with cholestasis. CONCLUSION: This case provided an opportunity to study
      the natural development of HCV during acute infection in the absence of an immune
      response, and may help to elucidate the pathogenesis of HCV recurrence in liver
      allografts.

PMID- 16443735
TI  - Caspase activity is downregulated in choriocarcinoma: a cDNA array differential
      expression study.
AB  - BACKGROUND: Placental trophoblast can be considered to be pseudomalignant tissue
      and the pathogenesis of gestational trophoblastic diseases remains to be
      clarified. AIMS: To examine the role of caspases 8 and 10, identified by
      differential expression, on trophoblast tumorigenesis. METHODS: cDNA array
      hybridisation was used to compare gene expression profiles in choriocarcinoma
      cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas,
      followed by confirmation with quantitative real time polymerase chain reaction
      and immunohistochemistry. Caspase 10 and its closely related family member
      caspase 8 were analysed. RESULTS: Downregulation of caspase 10 in choriocarcinoma
      was detected by both Atlastrade mark human cDNA expression array and Atlastrade
      mark human 1.2 array. Caspase 10 mRNA expression was significantly lower in
      hydatidiform mole (p = 0.035) and chorioarcinoma (p = 0.002) compared with normal
      placenta. The caspase 8 and 10 proteins were expressed predominantly in the
      cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower
      expression in choriocarcinomas than other trophoblastic tissues (p < 0.05).
      Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index
      previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick
      end labelling (p = 0.02 and p = 0.04, respectively) and M30 (p < 0.001 and p =
      0.003, respectively) approaches. CONCLUSIONS: These results suggest that the
      downregulation of capases 8 and 10 might contribute to the pathogenesis of
      choriocarcinoma.

PMID- 16443736
TI  - Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells
      induced by Toll-like receptor and ligand interaction.
AB  - BACKGROUND: The Toll-like receptor (TLR) family recognises pathogen associated
      molecular patterns (PAMPs) and plays a pivotal role in the innate immune
      response. Biliary epithelial cells (BECs) lining the intrahepatic bile ducts are
      potentially exposed to bacterial components in bile, and murine BECs possess TLRs
      that recognise PAMPs, resulting in nuclear factor kappaB (NF-kappaB) activation.
      AIMS: To examine the presence of TLRs in human BECs and the influence of
      cytokines and PAMPs on TLR expression and NF-kappaB activation. METHODS: The
      expression of TLR2-5, MD-2, MyD88, and IRAK1 was examined in human liver tissue
      and cultured BECs by immunohistochemistry or reverse transcription polymerase
      chain reaction. The influence of PAMPs (peptidoglycan and lipopolysaccharide) in
      cultured cells preincubated with interferon gamma (IFNgamma) was evaluated by NF
      kappaB activation. RESULTS: TLR2-5, MyD88, and IRAK-1 proteins were detectable in
      BECs of the intrahepatic biliary tree in human liver tissue. TLR2-5, MD-2, MyD88,
      and IRAK-1 mRNA was demonstrated in human cultured BECs. The expression of these
      TLRs was upregulated by IFNgamma, and TLR2 was upregulated by tumour necrosis
      factor alpha. Interleukins 4 and 6 failed to induce TLR upregulation.
      Interestingly, preincubation with IFNgamma synergistically increased the
      upregulation of NF-kappaB induced by PAMPs in cultured BECs. CONCLUSION: These
      results suggest that the TLR family is present in human biliary cells and
      participates in the innate immunity of the intrahepatic biliary tree. Disordered
      regulation of TLRs after intracellular signalling by cytokines and PAMPs may be
      involved in immune mediated biliary diseases.

PMID- 16443737
TI  - Lymphatic vessel density in the neoplastic progression of Barrett's oesophagus to
      adenocarcinoma.
AB  - BACKGROUND: Oesophageal adenocarcinoma is an aggressive neoplasm with poor
      prognosis as a result of early lymph node metastasis. AIMS: To measure lymphatic
      vessel density (LVD) in the neoplastic progression from Barrett's metaplasia to
      adenocarcinoma and determine whether LVD can predict the risk of cancer. In
      addition, to correlate LVD with lymph node metastasis and assess whether LVD
      could be used as a prognostic indicator for outcome or survival. METHODS: LVD and
      microvascular density (MVD) were assessed after immunohistochemical staining of
      vessels in Barrett's metaplasia, dysplasia, and adenocarcinoma tissues and were
      correlated with clinicopathological features. RESULTS: LVD was significantly
      reduced in adenocarcinoma, being half that seen in normal stomach/oesophagus or
      metaplasia/dysplasia. LVD did not correlate with tumour grade, stage, or clinical
      outcome; however, patients who had either lymph node metastasis or invasion of
      tumour cells into peritumorous lymphatic vessels had a significantly worse
      overall survival. MVD was also assessed as a prognostic marker; its increase
      appeared to be linked more with the development of Barrett's metaplasia than
      adenocarcinoma. CONCLUSIONS: The reduction in lymphatic vessel numbers was not
      useful for determining disease outcome in the patient group studied. It is the
      entry of tumour cells into pre-existing peritumorous lymphatic vessels that
      confers a significantly worse overall survival.

PMID- 16443738
TI  - Colocalisation of intraplaque C reactive protein, complement, oxidised low
      density lipoprotein, and macrophages in stable and unstable angina and acute
      myocardial infarction.
AB  - BACKGROUND: C reactive protein (CRP), an important serum marker of
      atherosclerotic vascular disease, has recently been reported to be active inside
      human atherosclerotic plaques. AIMS: To investigate the simultaneous presence of
      macrophages, CRP, membrane attack complex C5b-9 (MAC), and oxidised low density
      lipoprotein (oxLDL) in atherectomy specimens from patients with different
      coronary syndromes. METHODS: In total, 54 patients with stable angina (SA; n =
      21), unstable angina (UA; n = 15), and myocardial infarction (MI; n = 18)
      underwent directional coronary atherectomy for coronary lesions. Cryostat
      sections of atherosclerotic plaques were immunohistochemically stained with
      monoclonal antibodies: anti-CD68 (macrophages), anti-5G4 (CRP), aE11 (MAC), and
      12E7 (oxLDL). Immunopositive areas were evaluated in relation to fibrous and
      neointima tissues, atheroma, and media. Quantitative analysis was performed using
      image cytometry with systematic random sampling (percentage immunopositive/total
      tissue area). RESULTS: Macrophages, CRP, MAC, and oxLDL were simultaneously
      present in a higher proportion of fibrous tissue and atheroma of atherectomy
      specimens from patients with UA and MI compared with SA (p<0.05). Quantitative
      analysis showed significantly higher mean percentages of macrophages in plaques
      from patients with MI (44%) than UA (30%; p<0.01) and SA (20%; p<0.001).
      Significantly higher mean percentages of CRP were also seen in MI (25%) and UA
      (25%) compared with SA (12%; p<0.05). CONCLUSIONS: The presence of CRP,
      complement, and oxLDL in a high proportion of plaque tissue from patients with
      unstable coronary artery disease implies that these surrogate markers have
      important proinflammatory effects inside atherosclerotic plaques. This may
      increase vulnerability to plaque rupture and thrombosis, with subsequent clinical
      sequelae.

PMID- 16443739
TI  - Expression of IGF-I, IGF-II, and IGF-IR in gallbladder carcinoma. A systematic
      analysis including primary and corresponding metastatic tumours.
AB  - AIMS: The insulin-like growth factor (IGF) system has been implicated in tumour
      development and progression. This study was designed to analyse the expression of
      the IGF-I receptor (IGF-IR) and its ligands (IGF-I, IGF-II) in gallbladder
      cancer. METHODS: IGF-I, IGF-II, and IGF-IR immunoreactivity was investigated in
      57 gallbladder carcinomas and corresponding lymph node (n = 11) and hepatic (n =
      7) metastases using a tissue microarray technique and correlated with tumour
      stage, grade, and patient outcome. RESULTS: Cancer tissue allowing a reliable
      evaluation of IGF-I, IGF-II, and IGF-IR was present in 55 of 57 primary tumours
      and 17 of 18 metastases. IGF-I and IGF-II immunoreactivity was seen in 25 and 14
      of the 55 primary tumours, in addition to six and three of the 17 metastases,
      respectively. No associations with tumour stage, grade, or prognosis were
      detected. IGF-IR was expressed in 52 of 55 primary tumours and all 17 metastases.
      IGF-IR staining intensity decreased with tumour cell dedifferentiation. Moreover,
      IGF-IR expression in less than 50% of cancer cells was an independent marker of
      poor prognosis in multivariate analysis (risk ratio, 4.0; 95% confidence
      interval, 1.4 to 11.2; p = 0.01). CONCLUSIONS: The expression of IGF-IR and its
      ligands provides evidence for the existence of an auto/paracrine loop of tumour
      cell stimulation in gallbladder cancer and makes this type of cancer a candidate
      for therapeutic strategies aimed at interfering with the IGF pathway. The
      recognition of IGF-IR as a new independent prognostic biomarker may help to
      identify patients who might benefit from adjuvant treatment.

PMID- 16443740
TI  - Detection of venous invasion in surgical specimens of colorectal carcinoma: the
      efficacy of various types of tissue blocks.
AB  - BACKGROUND: Venous invasion (VI) is an important prognosis predictor after
      colorectal carcinoma (CRC) resection, enabling more accurate staging and
      influencing postoperative management. AIMS: To assess/compare various tissue
      block types (perpendicular, tangential, across mesentery (AM), from major vessels
      or lymph nodes (LNs)) for VI detection in CRC. METHODS: Fifty two CRCs (51
      colectomies, one polypectomy) were studied. Tumours were measured, surface area
      calculated, and colorectum and bowel wall sites recorded. Weigert's staining for
      elastin facilitated VI detection. VI sites, type, and amount were recorded.
      Ratios of relative yield of tissue block types to their frequency were
      calculated. RESULTS: Average numbers of tissue blocks/colectomy specimen were:
      perpendicular, 10.2; tangential, 9.1; AM, 3.3; from major vessels, 2.1. Average
      number of LNs examined was 16.47. VI was detected in 22 tumours. Overall, VI was
      detected in 16 perpendicular, seven tangential, five AM, and two LN blocks. VI
      was detected in eight, two, one, and three tumours in perpendicular, tangential,
      LN, and AM blocks alone, respectively. In seven tumours, VI was identified in
      multiple tissue block types. The average number of blocks obtained was 39.7,
      42.1, and 38 from all tumours, VI positive, and VI negative tumours, respectively
      (p = 0.0497). Efficacy to detect VI was 2.151, 2.088, 1.092, 0.172, and 0 for AM,
      perpendicular, tangential, LN, and mesenteric vessel blocks, respectively.
      CONCLUSIONS: VI was identified most frequently and in eight cases only in
      perpendicular blocks. However, extramural VI was detected in six tumours only in
      blocks cut tangentially, AM, or from harvested LNs. Hence, all these types of
      blocks should be submitted routinely and scanned for VI.

PMID- 16443741
TI  - Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory
      markers in patients with type 2 diabetes and peripheral arterial disease.
AB  - AIMS: To determine whether the G(-174)C interleukin 6 (IL-6) polymorphism
      influences the development of peripheral arterial disease (PAD) in individuals
      with type 2 diabetes. This was investigated by comparing the distribution of G(
      174)C genotypes between patients with type 2 diabetes and PAD (PAD+) and those
      with type 2 diabetes but without PAD (PAD-). Plasma concentrations of IL-6,
      fibrinogen, C reactive protein (CRP), and vascular endothelial growth factor
      (VEGF) were also compared in PAD+ and PAD- patients. METHODS: Blood samples were
      collected from 146 PAD+ and 144 PAD- patients. SfaNI was used to determine the G(
      174)C genotype. Plasma concentrations of IL-6, fibrinogen, CRP, and VEGF were
      measured by an enzyme linked immunosorbent assay. RESULTS: The GG genotype was
      more common in PAD+ patients than in PAD- patients. PAD+ patients also had
      increased mean plasma concentrations of IL-6, fibrinogen, CRP, and VEGF compared
      with PAD- patients. Mean plasma concentrations of IL-6, fibrinogen, and CRP in
      both PAD+ and PAD- patients were higher in those with the GG genotype than in
      those with the GC or CC genotypes. In contrast, mean plasma concentrations of
      VEGF in PAD+ and PAD- patients were not significantly different between those
      with different G(-174)C genotypes. CONCLUSIONS: These results support a model in
      which the GG genotype promotes PAD development among individuals with type 2
      diabetes by inducing increased release of IL-6. Higher concentrations of IL-6
      among those with the GG genotype is associated with increased plasma
      concentrations of fibrinogen and CRP.

PMID- 16443742
TI  - Small bowel infarction in a patient with coeliac disease.
AB  - A 40 year old man was admitted with a four week history of intractable diarrhoea
      and abdominal pain. A clinical diagnosis of inflammatory bowel disease was
      supported by biopsies of colonic mucosa. There was no response to Mesalazine and
      over 12 days the patient became critically ill with diarrhoea, hypovolaemia, and
      peritonism. A laparotomy was performed and 130 cm of infarcted ileum was
      resected. Extensive investigations excluded thrombophilia and echocardiography
      excluded intracardiac thrombus. Postoperatively the patient continued to have
      diarrhoea and he was diagnosed with coeliac disease on the basis of positive
      antiendomysial and antitissue transglutaminase autoantibodies and duodenal
      histology. Although there is no proof that mesenteric infarction occurred as a
      direct consequence of coeliac disease, clinicians should be aware of this
      possibility.

PMID- 16443743
TI  - Usefulness of the MicroSeq 500 16S rDNA bacterial identification system for
      identification of anaerobic Gram positive bacilli isolated from blood cultures.
AB  - Using full 16S ribosomal RNA (rRNA) gene sequencing as the gold standard, 20 non
      duplicating anaerobic Gram positive bacilli isolated from blood cultures were
      analysed by the MicroSeq 500 16S rDNA bacterial identification system. The
      MicroSeq system successfully identified 13 of the 20 isolates. Four and three
      isolates were misidentified at the genus and species level, respectively.
      Although the MicroSeq 500 16S rDNA bacterial identification system is better than
      three commercially available identification systems also evaluated, its database
      needs to be expanded for accurate identification of anaerobic Gram positive
      bacilli.

PMID- 16443744
TI  - Multilocular cystic renal oncocytoma.

PMID- 16443745
TI  - Talc induced pulmonary granulomatosis.

PMID- 16443746
TI  - The hair cycle.

PMID- 16443747
TI  - Wnt signaling: complexity at the surface.
AB  - Wnts are secreted proteins that are essential for a wide array of developmental
      and physiological processes. They signal across the plasma membrane by
      interacting with serpentine receptors of the Frizzled (Fz) family and members of
      the low-density-lipoprotein-related protein (LRP) family. Activation of Fz-LRP
      promotes the stability and nuclear localization of beta-catenin by compromising
      the ability of a multiprotein complex containing axin, adenomatosis polyposis
      coli (APC) and glycogen synthase kinase 3 (GSK3) to target it for degradation and
      block its nuclear import. The Fz-LRP receptor complex probably accomplishes this
      by generating multiple signals in the cytoplasm. These involve activation of
      Dishevelled (Dsh), possibly through trimeric G proteins and LRP-mediated axin
      binding and/or degradation. However, individual Wnts and Fzs can activate both
      beta-catenin-dependent and -independent pathways, and Fz co-receptors such as LRP
      probably provide some of this specificity. Additional, conflicting data concern
      the role of the atypical receptor tyrosine kinase Ryk, which might mediate Wnt
      signaling independently of Fz and/or function as a Fz co-receptor in some cells.

PMID- 16443748
TI  - Detergent-resistant membrane domains but not the proteasome are involved in the
      misfolding of a PrP mutant retained in the endoplasmic reticulum.
AB  - Inherited prion diseases are neurodegenerative pathologies related to genetic
      mutations in the prion protein (PrP) gene, which favour the conversion of PrP(C)
      into a conformationally altered pathogenic form, PrP(Sc). The molecular basis of
      PrP(C)/PrP(Sc) conversion, the intracellular compartment where it occurs and how
      this process leads to neurological dysfunction are not yet known. We have studied
      the intracellular synthesis, degradation and localization of a PrP mutant
      associated with a genetic form of Creutzfeldt-Jakob disease (CJD), PrPT182A, in
      transfected FRT cells. PrPT182A is retained in the endoplasmic reticulum (ER), is
      mainly associated with detergent-resistant microdomains (DRMs) and is partially
      resistant to proteinase K digestion. Although an untranslocated form of this
      mutant is polyubiquitylated and undergoes ER-associated degradation, the
      proteasome is not responsible for the degradation of its misfolded form,
      suggesting that it does not have a role in the pathogenesis of inherited
      diseases. On the contrary, impairment of PrPT182A association with DRMs by
      cholesterol depletion leads to its accumulation in the ER and substantially
      increases its misfolding. These data support the previous hypothesis that DRMs
      are important for the correct folding of PrP and suggest that they might have a
      protective role in pathological scrapie-like conversion of PrP mutants.

PMID- 16443749
TI  - Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal
      tension and mechanosensitive ion channels.
AB  - To understand how cells sense and adapt to mechanical stress, we applied
      tensional forces to magnetic microbeads bound to cell-surface integrin receptors
      and measured changes in bead displacement with sub-micrometer resolution using
      optical microscopy. Cells exhibited four types of mechanical responses: (1) an
      immediate viscoelastic response; (2) early adaptive behavior characterized by
      pulse-to-pulse attenuation in response to oscillatory forces; (3) later adaptive
      cell stiffening with sustained (>15 second) static stresses; and (4) a large
      scale repositioning response with prolonged (>1 minute) stress. Importantly,
      these adaptation responses differed biochemically. The immediate and early
      responses were affected by chemically dissipating cytoskeletal prestress
      (isometric tension), whereas the later adaptive response was not. The
      repositioning response was prevented by inhibiting tension through interference
      with Rho signaling, similar to the case of the immediate and early responses, but
      it was also prevented by blocking mechanosensitive ion channels or by inhibiting
      Src tyrosine kinases. All adaptive responses were suppressed by cooling cells to
      4 degrees C to slow biochemical remodeling. Thus, cells use multiple mechanisms
      to sense and respond to static and dynamic changes in the level of mechanical
      stress applied to integrins.

PMID- 16443750
TI  - Deficiency of centromere-associated protein Slk19 causes premature nuclear
      migration and loss of centromeric elasticity.
AB  - The cohesin complex prevents premature segregation of duplicated chromosomes by
      providing resistance to the pole-ward pull by spindle microtubules. The
      centromeric region (or sister kinetochores) bears the majority of this force and
      undergoes transient separation prior to anaphase, indicative of its elastic
      nature. A cysteine protease, separase, cleaves the cohesin subunit Scc1 and
      dissolves cohesion between sister chromatids, initiating their separation.
      Separase also cleaves the kinetochore protein Slk19 during anaphase. Slk19 has
      been implicated in stabilization of the mitotic spindle and regulation of mitotic
      exit, but it is not known what role it plays at the kinetochores. We show that
      during pre-anaphase arrest, the spindle in slk19Delta cells is excessively
      dynamic and the nuclei move into mother-daughter junction prematurely. As a
      result, the chromatin mass undergoes partial division that requires neither
      anaphase promoting complex (APC) activity nor Scc1 cleavage. Partial division of
      the chromatin mass is accompanied by the loss of the centromeric region's ability
      to resist pole-ward pull by the spindle. Slk19 physically associates with Scc1
      and this association appears necessary for efficient cleavage of Slk19 by
      separase. Our results suggest that Slk19 participates in regulating nuclear
      migration and, in conjunction with cohesin complex, may be involved in the
      maintenance of centromeric tensile strength to resist the pole-ward pull.

PMID- 16443751
TI  - The neuropeptide head activator is a high-affinity ligand for the orphan G
      protein-coupled receptor GPR37.
AB  - The neuropeptide head activator (HA) is a mitogen for mammalian cell lines of
      neuronal or neuroendocrine origin. HA signalling is mediated by a G-protein
      coupled receptor (GPCR). Orphan GPCRs with homology to peptide receptors were
      screened for HA interaction. Electrophysiological recordings in frog oocytes and
      in mammalian cell lines as well as Ca(2+) mobilisation assays revealed nanomolar
      affinities of HA to GPR37. HA signal transduction through GPR37 was mediated by
      an inhibitory G protein and required Ca(2+) influx through a channel of the
      transient receptor potential (TRP) family. It also required activation of Ca(2+)
      dependent calmodulin kinase and phosphoinositide 3-kinase. Respective inhibitors
      blocked HA signalling and HA-induced mitosis in GPR37-expressing cells. HA
      treatment resulted in internalisation of GPR37. Overexpression of GPR37 led to
      aggregate formation, retention of the receptor in the cytoplasm and low survival
      rates of transfected cells, confirming the notion that misfolded GPR37
      contributes to cell death, as observed in Parkinson's disease.

PMID- 16443752
TI  - Dictyostelium myosin-IE is a fast molecular motor involved in phagocytosis.
AB  - Class I myosins are single-headed motor proteins, implicated in various motile
      processes including organelle translocation, ion-channel gating, and cytoskeleton
      reorganization. Here we describe the cellular localization of myosin-IE and its
      role in the phagocytic uptake of solid particles and cells. A complete analysis
      of the kinetic and motor properties of Dictyostelium discoideum myosin-IE was
      achieved by the use of motor domain constructs with artificial lever arms. Class
      I myosins belonging to subclass IC like myosin-IE are thought to be tuned for
      tension maintenance or stress sensing. In contrast to this prediction, our
      results show myosin-IE to be a fast motor. Myosin-IE motor activity is regulated
      by myosin heavy chain phosphorylation, which increases the coupling efficiency
      between the actin and nucleotide binding sites tenfold and the motile activity
      more than fivefold. Changes in the level of free Mg(2+) ions, which are within
      the physiological range, are shown to modulate the motor activity of myosin-IE by
      inhibiting the release of adenosine diphosphate.

PMID- 16443753
TI  - EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture
      of medullary tubule cells through Rho family GTPases.
AB  - Eph receptors and ephrin ligands are membrane-bound cell-cell communication
      molecules with well-defined functions in development, but their expression
      patterns and functions in many adult tissues are still largely unknown. We have
      detected substantial levels of the EphB2 and EphB6 receptors and the ephrin-B1
      ligand in the adult mouse kidney by RT-PCR amplification. Immunolocalization
      experiments revealed that EphB2 is localized in the tubules of the inner and
      outer medulla and EphB6 is in the tubules of the outer medulla and cortex. By
      contrast, ephrin-B1 was detected in tubules throughout the whole nephron.
      Consistent with the overlapping expression of the EphB2 receptor and the ephrin
      B1 ligand in the medulla, EphB2 is tyrosine-phosphorylated, and therefore
      activated, in the kidney. In the outer medulla, however, EphB2 signaling may be
      attenuated by the co-expressed kinase-inactive EphB6 receptor. Interestingly, we
      found that EphB signaling induces RhoA activation and Rac1 inactivation as well
      as cell retraction, enlargement of focal adhesions and prominent stress fibers in
      primary cultures of medullary tubule cells. These results suggest that EphB
      receptor signaling through Rho family GTPases regulates the cytoarchitecture and
      spatial organization of the tubule cells in the adult kidney medulla and,
      therefore, may affect the reabsorption ability of the kidney.

PMID- 16443754
TI  - Phosphatidylinositol 4-kinase is required for endosomal trafficking and
      degradation of the EGF receptor.
AB  - The type II alpha isoform of phosphatidylinositol 4-kinase has recently been
      shown to function in the recruitment of adaptor protein-1 complexes to the trans
      Golgi network. Here we show that phosphatidylinositol 4-kinase IIalpha is also a
      component of highly dynamic membranes of the endosomal system where it
      colocalises with protein markers of the late endosome and with endocytosed
      epidermal growth factor. When phosphatidylinositol 4-kinase IIalpha activity was
      inhibited in vivo using the monoclonal antibody 4C5G or by depression of
      endogenous phosphatidylinositol 4-kinase IIalpha protein levels using RNA
      interference, ligand-bound epidermal growth factor receptor failed to traffic to
      late endosomes and instead accumulated in vesicles in a sub-plasma membrane
      compartment. Furthermore, lysosomal degradation of activated epidermal growth
      factor receptor was dramatically impaired in small inhibitory RNA-treated cells.
      We demonstrate that phosphatidylinositol 4-kinase IIalpha is necessary for the
      correct endocytic traffic and downregulation of activated epidermal growth factor
      receptor.

PMID- 16443756
TI  - The beta 2-adrenergic receptor activates pro-migratory and pro-proliferative
      pathways in dermal fibroblasts via divergent mechanisms.
AB  - Dermal fibroblasts are required for skin wound repair; they migrate into the
      wound bed, proliferate, synthesize extracellular matrix components and contract
      the wound. Although fibroblasts express beta2-adrenergic receptors (beta2-AR) and
      cutaneous keratinocytes can synthesize beta-AR agonists (catecholamines), the
      functional significance of this hormonal mediator network in the skin has not
      been addressed. Emerging studies from our laboratory demonstrate that beta2-AR
      activation modulates keratinocyte migration, essential for wound re
      epithelialization. Here we describe an investigation of the effects of beta2-AR
      activation on the dermal component of wound healing. We examined beta2-AR
      mediated regulation of biological processes in dermal fibroblasts that are
      critical for wound repair: migration, proliferation, contractile ability and
      cytoskeletal conformation. We provide evidence for the activation of at least two
      divergent beta2-AR-mediated signaling pathways in dermal fibroblasts, a Src
      dependent pro-migratory pathway, transduced through the epidermal growth factor
      receptor and extracellular signal-regulated kinase, and a PKA-dependent pro
      proliferative pathway. beta2-AR activation attenuates collagen gel contraction
      and alters the actin cytoskeleton and focal adhesion distribution through PKA
      dependent mechanisms. Our work uncovers a previously unrecognized role for the
      adrenergic hormonal mediator network in the cutaneous wound repair process.
      Exploiting these divergent beta2-AR agonist responses in cutaneous cells may
      generate novel therapeutic approaches for the control of wound healing.

PMID- 16443757
TI  - Adipose overexpression of phosphoenolpyruvate carboxykinase leads to high
      susceptibility to diet-induced insulin resistance and obesity.
AB  - Obesity and insulin resistance are associated with increased serum free fatty
      acids (FFAs). Thus, a reduction in circulating FFAs may increase insulin
      sensitivity. This could be achieved by increasing FFA reesterification in adipose
      tissue. Transgenic mice with increased adipose tissue glyceroneogenesis, caused
      by overexpression of phosphoenolpyruvate carboxykinase (PEPCK), show increased
      FFA reesterification and develop obesity but are insulin sensitive. Here, we
      examined whether these transgenic mice were protected from diet-induced insulin
      resistance. Surprisingly, when fed a high-fat diet for a short period (6 weeks),
      transgenic mice developed severe obesity and were more hyperinsulinemic, glucose
      intolerant, and insulin resistant than controls. The high triglyceride
      accumulation prevented white adipose tissue from buffering the flux of lipids in
      circulation and led to increased serum triglyceride levels and fat deposition in
      liver. Furthermore, circulating leptin and FFA concentrations increased to
      similar levels in transgenic and control mice, while adiponectin levels decreased
      in transgenic mice compared with controls. In addition, transgenic mice showed
      fat accumulation in brown adipose tissue, which decreased uncoupling protein-1
      expression, suggesting that these mice had impaired diet-induced thermogenesis.
      These results indicate that increased PEPCK expression in the presence of high
      fat feeding may have deleterious effects and lead to severe insulin resistance
      and type 2 diabetes.

PMID- 16443755
TI  - Glucocorticoid-induced osteogenesis is negatively regulated by Runx2/Cbfa1 serine
      phosphorylation.
AB  - Glucocorticoid hormones have complex stimulatory and inhibitory effects on
      skeletal metabolism. Endogenous glucocorticoid signaling is required for normal
      bone formation in vivo, and synthetic glucocorticoids, such as dexamethasone,
      promote osteoblastic differentiation in several in vitro model systems. The
      mechanism by which these hormones induce osteogenesis remains poorly understood.
      We demonstrate here that the coordinate action of dexamethasone and the
      osteogenic transcription factor Runx2/Cbfa1 synergistically induces osteocalcin
      and bone sialoprotein gene expression, alkaline phosphatase activity, and
      biological mineral deposition in primary dermal fibroblasts. Dexamethasone
      decreased Runx2 phosphoserine levels, particularly on Ser125, in parallel with
      the upregulation of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1)
      through a glucocorticoid-receptor-mediated mechanism. Inhibition of MKP-1
      abrogated the dexamethasone-induced decrease in Runx2 serine phosphorylation,
      suggesting that glucocorticoids modulate Runx2 phosphorylation via MKP-1.
      Mutation of Ser125 to glutamic acid, mimicking constitutive phosphorylation,
      inhibited Runx2-mediated osteoblastic differentiation, which was not rescued by
      dexamethasone treatment. Conversely, mutation of Ser125 to glycine, mimicking
      constitutive dephosphorylation, markedly increased osteoblastic differentiation,
      which was enhanced by, but did not require, additional dexamethasone
      supplementation. Collectively, these results demonstrate that dexamethasone
      induces osteogenesis, at least in part, by modulating the phosphorylation state
      of a negative-regulatory serine residue (Ser125) on Runx2. This work identifies a
      novel mechanism for glucocorticoid-induced osteogenic differentiation and
      provides insights into the role of Runx2 phosphorylation during skeletal
      development.

PMID- 16443758
TI  - Inhibition of p38MAPK increases adipogenesis from embryonic to adult stages.
AB  - Formation of new adipocytes from precursor cells contributes to adipose tissue
      expansion and obesity. In this study, we asked whether p38 mitogen-activated
      protein kinase (MAPK) pathway regulates normal and pathological adipogenesis. In
      both dietary and genetically (ob/ob) obese mice, adipose tissues displayed a
      marked decrease in p38MAPK activity compared with the same tissues from lean
      mice. Furthermore, p38MAPK activity was significantly higher in preadipocytes
      than in adipocytes, suggesting that p38MAPK activity decreases during adipocyte
      differentiation. In agreement with an inhibitory role of p38MAPK in this process,
      we found that in vitro inhibition of p38MAPK, with the specific inhibitor
      PD169316, increased the expression of adipocyte markers in several cellular
      models, from embryonic to adult stages. Importantly, the expression of adipocyte
      markers was higher in p38MAPKalpha knockout cells than in their wild-type
      counterparts. Phosphorylation of C/EBPbeta, which enhances its transcriptional
      activity, is increased after p38MAPK inhibition. Finally, either inhibition or
      disruption of p38MAPK increased peroxisome proliferator-activated receptor
      (PPAR)gamma expression and transactivation. Rescue of p38MAPK in knockout cells
      reduced PPARgamma activity to the low basal level of wild-type cells. We
      demonstrate here, by using multipronged approaches involving p38 chemical
      inhibitor and p38MAPKalpha knockout cells, that p38MAPK plays a negative role in
      adipogenesis via inhibition of C/EBPbeta and PPARgamma transcriptional
      activities.

PMID- 16443759
TI  - Failure of transplanted bone marrow cells to adopt a pancreatic beta-cell fate.
AB  - Recent studies in normal mice have suggested that transplanted bone marrow cells
      can transdifferentiate into pancreatic beta-cells at relatively high efficiency.
      Herein, adopting the same and alternative approaches to deliver and fate map
      transplanted bone marrow cells in the pancreas of normal as well as diabetic
      mice, we further investigated the potential of bone marrow transplantation as an
      alternative approach for beta-cell replacement. In contrast to previous studies,
      transplanted bone marrow cells expressing green fluorescence protein (GFP) under
      the control of the mouse insulin promoter failed to express GFP in the pancreas
      of normal as well as diabetic mice. Although bone marrow cells expressing GFP
      under the ubiquitously expressed beta-actin promoter efficiently engrafted the
      pancreas of normal and hyperglycemic mice, virtually all expressed CD45 and Mac
      1/Gr-1, demonstrating that they adopt a hematopoietic rather than beta-cell fate,
      a finding further substantiated by the complete absence of GFP(+) cells
      expressing insulin and the beta-cell transcription factors pancreatic duodenal
      homeobox factor-1 and homeodomain protein. Thus, transplanted bone marrow cells
      demonstrated little, if any, capacity to adopt a beta-cell fate.

PMID- 16443760
TI  - MafB: an activator of the glucagon gene expressed in developing islet alpha- and
      beta-cells.
AB  - The large Maf family of basic leucine-zipper-containing transcription factors are
      known regulators of key developmental and functional processes in various cell
      types, including pancreatic islets. Here, we demonstrate that within the adult
      pancreas, MafB is only expressed in islet alpha-cells and contributes to cell
      type-specific expression of the glucagon gene through activation of a conserved
      control element found between nucleotides -77 to -51. MafB was also shown to be
      expressed in developing alpha- and beta-cells as well as in proliferating hormone
      negative cells during pancreatogenesis. In addition, MafB expression is
      maintained in the insulin(+) and glucagon(+) cells remaining in mice lacking
      either the Pax4 or Pax6 developmental regulators, implicating a potentially early
      role for MafB in gene regulation during islet cell development. These results
      indicate that MafB is not only important to islet alpha-cell function but may
      also be involved in regulating genes required in both endocrine alpha- and beta
      cell differentiation.

PMID- 16443761
TI  - CART regulates islet hormone secretion and is expressed in the beta-cells of type
      2 diabetic rats.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic peptide
      widely expressed in the central, peripheral, and enteric nervous systems. CART is
      also expressed in endocrine cells, including beta-cells during rat development
      and delta-cells of adult rats. We examined the effect of CART 55-102 on islet
      hormone secretion, using INS-1(832/13) cells and isolated rat islets. In
      addition, islet CART expression was examined in two rat models of type 2
      diabetes: Goto-Kakizaki (GK) rats and dexamethasone (DEX)-treated rats. At high
      glucose, CART potentiated cAMP-enhanced insulin secretion via the cAMP/protein
      kinase A-dependent pathway. In the absence of cAMP-elevating agents, CART was
      without effect on INS-1 cells but modestly inhibited secretion of insulin,
      glucagon, and somatostatin from isolated islets. CART was markedly upregulated in
      the beta-cells of both diabetes models. Thus, in DEX-treated rats, islet CART
      mRNA expression, and the number of CART-immunoreactive beta-cells were 10-fold
      higher than in control rats. In GK rats, the relative number of CART-expressing
      beta-cells was 30-fold higher than in control rats. We conclude that CART is a
      regulator of islet hormone secretion and that CART is upregulated in the beta
      cells of type 2 diabetic rats.

PMID- 16443762
TI  - Integrin signaling via RGD peptides and anti-beta1 antibodies confers resistance
      to apoptosis in islets of Langerhans.
AB  - Islet transplantation is associated with a high rate of early graft failure
      caused by early immune attack and poor functionality of islets. Apoptosis of
      islet cells appears soon after islet isolation and primarily involves the beta
      cell. The purpose of this study was to determine the effect of ligation to
      extracellular matrix (ECM) proteins on survival of the islets of Langerhans
      following islet isolation. Islets that had been cultured for 24 h on collagen
      type I showed an islet survival of 59.7 +/- 8.7%, while islets that had been
      cultured on collagen type IV and laminin showed an islet survival of 88.6 +/-
      10.3 and 94.3 +/- 5.6%, respectively. Islets that had been pretreated with anti
      beta1 antibodies and argenin-glycin-aspartic acid (RGD) peptides showed a
      decrease in the level of apoptosis by a factor of 2.5 and 3.1, respectively, and
      an increase of phospho-Akt Ser 473 activity by a factor of 3.1 and 2.9,
      respectively, compared with untreated islets. When detached from their natural
      ECM surrounding in the pancreas, islet cells undergo apoptosis, unless islets are
      cultured on collagen IV or laminin or treated with anti-beta1 integrin antibodies
      or RGD peptides to mimic ECM ligation. These results indicate that inhibition of
      anoikis may offer opportunities to improve function and viability of islet cells.

PMID- 16443763
TI  - Akt induces beta-cell proliferation by regulating cyclin D1, cyclin D2, and p21
      levels and cyclin-dependent kinase-4 activity.
AB  - Proliferation is the major component for maintenance of beta-cell mass in adult
      animals. Activation of phosphoinositide 3-kinase/Akt-kinase pathway is a critical
      regulator of beta-cell mass. Pancreatic beta-cell overexpression of
      constitutively active Akt in mice (caAkt(Tg)) resulted in marked expansion of
      beta-cell mass by increase in beta-cell proliferation and size. The current
      studies provide new insights into the molecular mechanisms involved in beta-cell
      proliferation by Akt. Proliferation of beta-cells in caAkt(Tg) was associated
      with increased cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4
      (cdk4) activity. To determine the role of cdk4 in beta-cell proliferation induced
      by Akt, we generated caAkt(Tg) mice that were homozygous, heterozygous, or
      nullizygous for cdk4. The results of these studies showed that deletion of one
      cdk4 allele significantly reduced beta-cell expansion in caAkt(Tg) mice by
      decreased proliferation. CaAkt(Tg) mice deficient in cdk4 developed beta-cell
      failure and diabetes. These experiments suggest that Akt induces beta-cell
      proliferation in a cdk4-dependent manner by regulation of cyclin D1, cyclin D2,
      and p21 levels. These data also indicate that alteration in levels of these cell
      cycle components could affect the maintenance of beta-cell mass in basal states
      and the adaptation of beta-cells to pathological states resulting in diabetes.

PMID- 16443764
TI  - Effects of type 1 diabetes on gray matter density as measured by voxel-based
      morphometry.
AB  - The effects of type 1 diabetes and key metabolic variables on brain structure are
      not well understood. Sensitive methods of assessing brain structure, such as
      voxel-based morphometry (VBM), have not previously been used to investigate
      central nervous system changes in a diabetic population. Using VBM, we compared
      type 1 diabetic patients aged 25-40 years with disease duration of 15-25 years
      and minimal diabetes complications with an age-matched, nondiabetic control
      group. We investigated whether lower than expected gray matter densities were
      present, and if so, whether they were associated with glycemic control and
      history of severe hypoglycemic events. In comparison with control subjects,
      diabetic patients showed lower density of gray matter in several brain regions.
      Moreover, in the patient group, higher HbA(1c) levels and severe hypoglycemic
      events were associated with lower density of gray matter in brain regions
      responsible for language processing and memory. Our study represents the first
      comprehensive study of gray matter density changes in type 1 diabetes and
      suggests that persistent hyperglycemia and acute severe hypoglycemia have an
      impact on brain structure.

PMID- 16443765
TI  - Microvascular disease in type 1 diabetes alters brain activation: a functional
      magnetic resonance imaging study.
AB  - Individuals with type 1 diabetes have mild performance deficits on a range of
      neuropsychological tests compared with nondiabetic control subjects. The
      mechanisms underlying this cognitive deterioration are still poorly understood,
      but chronic hyperglycemia is now emerging as a potential determinant, possibly
      through microvascular changes in the brain. In 24 type 1 diabetic patients, we
      tested at euglycemia and at acute hypoglycemia whether the presence of
      proliferative diabetic retinopathy, as a marker of microvascular disease,
      adversely affects the ability of the brain to respond to standardized
      hypoglycemia, using functional magnetic resonance imaging with a cognitive task.
      Patients with retinopathy, compared with patients without, showed less
      deactivation (hence, an increased response) in the anterior cingulate and the
      orbital frontal gyrus during hypoglycemia compared with euglycemia (P < 0.05).
      Task performance and reaction time were not significantly different for either
      group. We conclude that microvascular damage in the brain of patients with
      retinopathy caused this increased brain response to compensate for functional
      loss.

PMID- 16443766
TI  - ACE inhibitor or angiotensin II receptor antagonist attenuates diabetic
      neuropathy in streptozotocin-induced diabetic rats.
AB  - ACE inhibition and/or blocking of the angiotensin II receptor are recognized as
      first-line treatment for nephropathy and cardiovascular disease in diabetic
      patients. However, little information is available about the potential benefits
      of these drugs on diabetic neuropathy. We examined vascular and neural activity
      in streptozotocin-induced diabetic rats that were treated for 12 weeks with
      enalapril, an ACE inhibitor, or L-158809, an angiotensin II receptor blocker. A
      prevention protocol (group 1) as well as three intervention protocols (treatment
      was initiated after 4, 8, or 12 weeks of diabetes [groups 2, 3, and 4,
      respectively]) were used. Endoneurial blood flow and motor nerve conduction
      velocity (MNCV) were impaired in all groups of untreated diabetic rats. In group
      1, treatment of diabetic rats with enalapril or L-158809 partially prevented the
      diabetes-induced decrease in endoneurial blood flow and MNCV. In groups 2-4,
      intervention with enalapril was more effective in reversing the diabetes-induced
      impairment in endoneurial blood flow and MNCV than L-158809. The superoxide level
      in the aorta and epineurial arterioles of diabetic rats was increased. Treatment
      of diabetic rats with enalapril or L-158809 reduced the superoxide level in the
      aorta in all groups but was less effective in epineurial arterioles.
      Acetylcholine and calcitonin gene-related peptide (CGRP) cause vasodilation in
      epineurial arterioles of the sciatic nerve, which was impaired by diabetes.
      Treatment of diabetic rats (all groups) with enalapril or L-158809 completely
      prevented/reversed the diabetes-induced impairment in CGRP-mediated vascular
      relaxation. Treatment with enalapril or L-158809 was also effective in improving
      impaired acetylcholine-mediated vasodilation, but the efficacy was diminished
      from groups 1 to 4. These studies suggest that ACE inhibitors and/or angiotensin
      II receptor blockers may be effective treatments for diabetes and vascular and
      neural dysfunction. However, the efficacy of these treatments may be dependent on
      when the treatment is initiated.

PMID- 16443767
TI  - Streptozotocin-induced diabetes causes astrocyte death after ischemia and
      reperfusion injury.
AB  - Diabetes exacerbates neuronal cell death induced by cerebral ischemia. One
      contributing factor is enhanced acidosis during ischemia. Astrocytes are
      vulnerable to hypoxia under acidic conditions in vitro and may be targets of
      ischemia under diabetic conditions. The objective of this study was to determine
      whether diabetes would cause damage to astrocytes after an ischemic brain injury
      in vivo. Diabetic and nondiabetic rats were subjected to 5 min of forebrain
      ischemia and followed by 30 min, 6 h, or 1 or 3 days of recovery. The results
      showed that ischemia caused activation of astrocytes in nondiabetic rats. In
      contrast, diabetes caused astrocyte activation in early stage of reperfusion and
      astrocyte death in late stage of reperfusion. Remarkable astrocyte death was
      preceded by increased DNA oxidation. Further studies revealed that increased
      astrocyte damage coincided with enhanced production of free radicals. These data
      suggest that hyperglycemic ischemia worsens outcome in astrocytes, as it does in
      neurons.

PMID- 16443768
TI  - A severe diabetic nephropathy model with early development of nodule-like lesions
      induced by megsin overexpression in RAGE/iNOS transgenic mice.
AB  - Many factors are involved in the pathogenesis of diabetic nephropathy. A single
      gene abnormality may be prerequisite but insufficient to the disease to manifest.
      It is therefore only when a second or sometimes a third damage is associated that
      the consequences of pathogenic phenotypes become evident. We generated the triple
      transgenic mice overexpressing megsin (a novel glomerular-specific serpin), a
      receptor for advanced glycation end products (RAGE), and inducible nitric oxide
      synthase (iNOS). Compared with the single- or two-gene transgenic mice, the
      triple transgenic mice developed, at an early age (16 weeks), severe albuminuria
      and renal damage with all of the characteristics of human diabetic nephropathy
      (i.e., glomerular hypertrophy, diffuse mesangial expansion, inflammatory cell
      infiltration, and interstitial fibrosis). Interestingly, 30-40% of glomeruli
      exhibit nodule-like lesions. Oxidative and carbonyl stress makers (pentosidine,
      N(epsilon)-carboxymethyllysine, and 8-hydroxy-deoxyguanosine) were significantly
      higher in the triple transgenic mice. The iNOS transgenic mice have a diabetes
      phenotype, the renal consequences of which are moot, and the superimposition of
      RAGE leads to more conspicuous manifestations. By additional overexpression of
      megsin, a gene known to be involved in mesangial proliferation and expansion,
      these local consequences become dramatically manifest and approximate those
      observed in human pathology. This multiple hit approach is of interest in
      consideration of the sequential events during development of diabetic
      nephropathy.

PMID- 16443769
TI  - Angiotensin II type 1 receptor blockade improves beta-cell function and glucose
      tolerance in a mouse model of type 2 diabetes.
AB  - We identified an angiotensin-generating system in pancreatic islets and found
      that exogenously administered angiotensin II, after binding to its receptors
      (angiotensin II type 1 receptor [AT1R]), inhibits insulin release in a manner
      associated with decreased islet blood flow and (pro)insulin biosynthesis. The
      present study tested the hypothesis that there is a change in AT1R expression in
      the pancreatic islets of the obesity-induced type 2 diabetes model, the db/db
      mouse, which enables endogenous levels of angiotensin II to impair islet
      function. Islets from 10-week-old db/db and control mice were isolated and
      investigated. In addition, the AT1R antagonist losartan was administered orally
      to 4-week-old db/db mice for an 8-week period. We found that AT1R mRNA was
      upregulated markedly in db/db islets and double immunolabeling confirmed that the
      AT1R was localized to beta-cells. Losartan selectively improved glucose-induced
      insulin release and (pro)insulin biosynthesis in db/db islets. Oral losartan
      treatment delayed the onset of diabetes, and reduced hyperglycemia and glucose
      intolerance in db/db mice, but did not affect the insulin sensitivity of
      peripheral tissues. The present findings indicate that AT1R antagonism improves
      beta-cell function and glucose tolerance in young type 2 diabetic mice. Whether
      islet AT1R activation plays a role in the pathogenesis of human type 2 diabetes
      remains to be determined.

PMID- 16443770
TI  - Genetic architecture of the APM1 gene and its influence on adiponectin plasma
      levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians.
AB  - The associations of the adiponectin (APM1) gene with parameters of the metabolic
      syndrome are inconsistent. We performed a systematic investigation based on fine
      mapped single nucleotide polymorphisms (SNPs) highlighting the genetic
      architecture and their role in modulating adiponectin plasma concentrations in a
      particularly healthy population of 1,727 Caucasians avoiding secondary effects
      from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the
      APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium
      (LD) structure and enabled comprehensive tag SNP selection. We found particularly
      strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in
      the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a
      thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes
      showing significant associations (three P values <0.0001). No significant
      association was found for any SNP with the parameters of the metabolic syndrome.
      We observed a two-block LD structure of APM1 pointing toward at least two
      independent association signals, one including the promoter SNPs and a second
      spanning the relevant exons. Our data on a large number of healthy subjects
      suggest a clear modulation of adiponectin concentrations by variants of APM1,
      which are not merely a concomitant effect in the course of type 2 diabetes or
      coronary artery disease.

PMID- 16443771
TI  - Identification of TUB as a novel candidate gene influencing body weight in
      humans.
AB  - Previously, we identified a locus on 11p influencing obesity in families with
      type 2 diabetes. Based on mouse studies, we selected TUB as a functional
      candidate gene and performed association studies to determine whether this
      controls obesity. We analyzed the genotypes of 13 single nucleotide polymorphisms
      (SNPs) around TUB in 492 unrelated type 2 diabetic patients with known BMI
      values. One SNP (rs1528133) was found to have a significant effect on BMI (1.54
      kg/m(2), P = 0.006). This association was confirmed in a population enriched for
      type 2 diabetes, using 750 individuals who were not selected for type 2 diabetes.
      Two SNPs in linkage disequilibrium with rs1528133 and mapping to the 3' end of
      TUB, rs2272382, and rs2272383 also affected BMI by 1.3 kg/m2 (P = 0.016 and P =
      0.010, respectively). Combined analysis confirmed this association (P = 0.005 and
      P = 0.002, respectively). Moreover, comparing 349 obese subjects (BMI >30
      kg/m(2)) from the combined cohort with 289 normal subjects (BMI <25 kg/m(2))
      revealed that the protective alleles have a lower frequency in obese subjects
      (odds ratio 1.32 [95% CI 1.04-1.67], P = 0.022). Altogether, data from the tubby
      mouse as well as these data suggest that TUB could be an important factor in
      controlling the central regulation of body weight in humans.

PMID- 16443772
TI  - Considerations in the design of hyperinsulinemic-euglycemic clamps in the
      conscious mouse.
AB  - Despite increased use of the hyperinsulinemic-euglycemic clamp to study insulin
      action in mice, the effects of experimental parameters on the results obtained
      have not been addressed. In our studies, we determined the influences of sampling
      sites, fasting duration, and insulin delivery on results obtained from clamps in
      conscious mice. Carotid artery and jugular vein catheters were implanted in
      C57BL/6J mice (n = 6-10/group) fed a normal diet for sampling and infusions.
      After a 5-day recovery period, mice underwent a 120-min clamp (2.5-mU . kg(-1) .
      min(-1) insulin infusion; approximately 120-130 mg/dl glucose) while receiving [3
      (3)H]glucose to determine glucose appearance (endoR(a)) and disappearance (R(d)).
      Sampling large volumes (approximately 100 mul) from the cut tail resulted in
      elevated catecholamines and basal glucose compared with artery sampling.
      Catecholamines were not elevated when taking small samples ( approximately 5 mul)
      from the cut tail. Overnight (18-h) fasting resulted in greater loss of total
      body, lean, and fat masses and hepatic glycogen but resulted in enhanced insulin
      sensitivity compared with 5-h fasting. Compared with a 16-mU/kg insulin prime, a
      300-mU/kg prime resulted in hepatic insulin resistance and slower acquisition of
      steady-state glucose infusion rates (GIR) after a 5-h fast. The steady-state GIR
      was expedited after the 300-mU/kg prime in 18-h-fasted mice. The GIR and R(d)
      rose with increasing insulin infusions (0.8, 2.5, 4, and 20 mU . kg(-1) . min(
      1)), but endoR(a) was fully suppressed with doses higher than 0.8 mU . kg(-1) .
      min(-1). Thus, common variations in experimental factors yield different results
      and should be considered in designing and interpreting clamps.

PMID- 16443773
TI  - Cholinergic involvement in vascular and glucoregulatory actions of insulin in
      rats.
AB  - This study was designed to test the glucose metabolic and vasodilator actions of
      insulin in rats and its relation to cholinergic system-dependent mechanisms. The
      first group of rats had pulsed Doppler flow probes and intravascular catheters
      implanted to determine blood pressure, heart rate, and regional blood flows.
      Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp
      technique carried out in the absence or presence of atropine. The second group of
      rats was used to determine the cholinergic contribution to in vivo insulin
      mediated glucose utilization in individual muscles. Glucose uptake was examined
      by using [(3)H]2-deoxy-D-glucose. Muscarinic cholinergic blockade was found to
      significantly (P = 0.002) reduce insulin sensitivity and to completely abrogate
      the renal (P = 0.008) and hindquarter (P = 0.02) vasodilator responses to
      euglycemic infusion of insulin. A significant reduction in insulin-stimulated in
      vivo glucose uptake was also noted in soleus (P = 0.006), quadriceps (P = 0.03),
      gastrocnemius (P = 0.02), and extensor digitorum longus (EDL) (P = 0.001)
      muscles, when insulin was infused at a rate of 4 mU . kg(-1) . min(-1), whereas
      at the rate of 16 mU . kg(-1) . min(-1), a significant reduction in glucose
      uptake was only observed in EDL (P = 0.03) and quadriceps (P = 0.01) muscles.
      Together, these results demonstrate a potential role for cholinergic involvement
      with physiological insulin actions in glucose clearance and blood flow regulation
      in rats.

PMID- 16443774
TI  - Contrasting insulin sensitivity of endogenous glucose production rate in subjects
      with hepatocyte nuclear factor-1beta and -1alpha mutations.
AB  - Heterozygous mutations in the transcription factors hepatocyte nuclear factor
      (HNF)-1alpha and -1beta result in MODY (maturity-onset diabetes of the young).
      Despite structural similarity between HNF-1alpha and -1beta, HNF-1beta mutation
      carriers have hyperinsulinemia, whereas HNF-1alpha mutation carriers have normal
      or reduced insulin concentrations. We examined whether HNF-1beta mutation
      carriers are insulin resistant. The endogenous glucose production rate and rate
      of glucose uptake were measured with a two-step, low-dose (0.3 mU . kg(-1) . min(
      1)) and high-dose (1.5 mU . kg(-1) . min(-1)) hyperinsulinemic-euglycemic clamp,
      with an infusion of [6,6-(2)H(2)]glucose, in six subjects with HNF-1alpha
      mutations, six subjects with HNF-1beta mutations, and six control subjects,
      matched for age, sex, and BMI. Endogenous glucose production rate was not
      suppressed by low-dose insulin in HNF-1beta subjects but was suppressed by 89% in
      HNF-1alpha subjects (P = 0.004) and 80% in control subjects (P < 0.001). Insulin
      stimulated glucose uptake and suppression of lipolysis were similar in all groups
      at low- and high-dose insulin. Subjects with HNF-1beta mutations have reduced
      insulin sensitivity of endogenous glucose production but normal peripheral
      insulin sensitivity. This is likely to reflect reduced action of HNF-1beta in the
      liver and possibly the kidney. This may be mediated through regulation by HNF
      1beta of the key gluconeogenic enzymes glucose-6-phosphatase or PEPCK.

PMID- 16443776
TI  - SGK1 kinase upregulates GLUT1 activity and plasma membrane expression.
AB  - Phosphatidylinositol 3-kinase (PI3 kinase) inhibition disrupts the ability of
      insulin to stimulate GLUT1 and GLUT4 translocation into the cell membrane and
      thus glucose transport. The effect on GLUT4 but not on GLUT1 is mediated by
      activation of protein kinase B (PKB). The serum- and glucocorticoid-inducible
      kinase SGK1, a further kinase downstream of PI3 kinase, regulates several
      transporters by enhancing their plasma membrane abundance. GLUT1 contains a
      consensus site ((95)Ser) for phosphorylation by SGK1. Thus, the present study
      investigated whether GLUT1 is regulated by the kinase. Tracer-flux studies in
      Xenopus oocytes and HEK-293 cells demonstrated that GLUT1 transport is enhanced
      by constitutively active (S422D)SGK1. The effect requires the kinase catalytical
      activity since the inactive mutant (K127N)SGK1 failed to modulate GLUT1. GLUT1
      stimulation by (S422D)SGK1 is not due to de novo protein synthesis but rather to
      an increase of the transporter's abundance in the plasma membrane. Kinetic
      analysis revealed that SGK1 enhances maximal transport rate without altering
      GLUT1 substrate affinity. These observations suggest that SGK1 regulates GLUT1
      and may contribute to or account for the PI3 kinase-dependent but PKB-independent
      stimulation of GLUT1 by insulin.

PMID- 16443775
TI  - Glucokinase is a critical regulator of ventromedial hypothalamic neuronal
      glucosensing.
AB  - To test the hypothesis that glucokinase is a critical regulator of neuronal
      glucosensing, glucokinase activity was increased, using a glucokinase activator
      drug, or decreased, using RNA interference combined with calcium imaging in
      freshly dissociated ventromedial hypothalamic nucleus (VMN) neurons or primary
      ventromedial hypothalamus (VMH; VMN plus arcuate nucleus) cultures. To assess the
      validity of our approach, we first showed that glucose-induced (0.5-2.5 mmol/l)
      changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations, using
      fura-2 and changes in membrane potential (using a membrane potential-sensitive
      dye), were highly correlated in both glucose-excited and -inhibited neurons.
      Also, glucose-excited neurons increased (half-maximal effective concentration
      [EC(50)] = 0.54 mmol/l) and glucose-inhibited neurons decreased (half-maximal
      inhibitory concentration [IC(50)] = 1.12 mmol/l) [Ca(2+)](i) oscillations to
      incremental changes in glucose from 0.3 to 5 mmol/l. In untreated primary VMH
      neuronal cultures, the expression of glucokinase mRNA and the number of
      demonstrable glucosensing neurons fell spontaneously by half over 12-96 h without
      loss of viable neurons. Transfection of neurons with small interfering
      glucokinase RNA did not affect survival but did reduce glucokinase mRNA by 90% in
      association with loss of all demonstrable glucose-excited neurons and a 99%
      reduction in glucose-inhibited neurons. A pharmacological glucokinase activator
      produced a dose-related increase in [Ca(2+)](i) oscillations in glucose-excited
      neurons (EC(50) = 0.98 mmol/l) and a decrease in glucose-inhibited neurons
      (IC(50) = 0.025 micromol/l) held at 0.5 mmol/l glucose. Together, these data
      support a critical role for glucokinase in neuronal glucosensing.

PMID- 16443777
TI  - MCH-/- mice are resistant to aging-associated increases in body weight and
      insulin resistance.
AB  - Ablation of the hypothalamic peptide, melanin-concentrating hormone (MCH), leads
      to a lean phenotype and resistance to diet-induced obesity. Observation of MCH(-/
      ) mice at older ages suggested that these effects persist in mice >1 year old.
      Leanness secondary to caloric restriction is known to be associated with improved
      glucose tolerance as well as an overall increase in life span. Because the MCH(-/
      ) model represents leanness secondary to increased energy expenditure rather than
      caloric restriction, we were interested in determining whether this model of
      leanness would be associated with beneficial metabolic effects at older ages. To
      assess the effects of MCH ablation over a more prolonged period, we monitored
      male and female MCH(-/-) mice up to 19 months. The lean phenotype of MCH(-/-)
      mice persisted over the duration of the study. At 19 months, MCH(-/-) male and
      female mice weighed 23.4 and 30.8% less than their wild-type counterparts, a
      result of reduced fat mass in MCH(-/-) mice. Aged MCH(-/-) mice exhibited better
      glucose tolerance and were more insulin sensitive compared with wild-type
      controls. Aging-associated decreases in locomotor activity were also attenuated
      in MCH(-/-) mice. We also evaluated two molecules implicated in the
      pathophysiology of aging, p53 and silent inflammatory regulator 2 (Sir2). We
      found that expression of the tumor suppressor protein p53 was higher in MCH(-/-)
      mice at 9 and 19 months of age. In contrast, expression of Sir2 was unchanged. In
      aggregate, these findings suggest that MCH ablation improves the long-term
      outcome for several indicators of the aging process.

PMID- 16443778
TI  - Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide
      attachment protein receptor complex proteins in pancreatic islets of type 2
      diabetic patients.
AB  - Exocytosis of insulin is dependent on the soluble N-ethylmaleimide attachment
      protein receptor (SNARE) complex proteins in the B-cells. We assessed insulin
      release as well as gene and protein expression of SNARE complex protein in
      isolated pancreatic islets of type 2 diabetic patients (n = 4) and nondiabetic
      control subjects (n = 4). In islets from the diabetic patients, insulin responses
      to 8.3 and 16.7 mmol/l glucose were markedly reduced compared with control islets
      (4.7 +/- 0.3 and 8.4 +/- 1.8 vs. 17.5 +/- 0.1 and 24.3 +/- 1.2 microU . islet(-1)
      . h(-1), respectively; P < 0.001). Western blot analysis revealed decreased
      amounts of islet SNARE complex and SNARE-modulating proteins in diabetes:
      syntaxin-1A (21 +/- 5% of control levels), SNAP-25 (12 +/- 4%), VAMP-2 (7 +/-
      4%), nSec1 (Munc 18; 34 +/- 13%), Munc 13-1 (27 +/- 4%), and synaptophysin (64 +/
      7%). Microarray gene chip analysis, confirmed by quantitative PCR, showed that
      gene expression was decreased in diabetes islets: syntaxin-1A (27 +/- 2% of
      control levels), SNAP-25 (31 +/- 7%), VAMP-2 (18 +/- 3%), nSec1 (27 +/- 5%),
      synaptotagmin V (24 +/- 2%), and synaptophysin (12 +/- 2%). In conclusion, these
      data support the view that decreased islet RNA and protein expression of SNARE
      and SNARE-modulating proteins plays a role in impaired insulin secretion in type
      2 diabetic patients. It remains unclear, however, to which extent this defect is
      primary or secondary to, e.g., glucotoxicity.

PMID- 16443779
TI  - In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse:
      pattern and role of cytoplasmic Ca2+ and amplification signals in beta-cells.
AB  - The mechanisms underlying biphasic insulin secretion have not been completely
      elucidated. We compared the pattern of plasma insulin changes during
      hyperglycemic clamps in mice to that of glucose-induced insulin secretion and
      cytosolic calcium concentration ([Ca(2+)](c)) changes in perifused mouse islets.
      Anesthetized mice were infused with glucose to clamp blood glucose at 8.5
      (baseline), 11.1, 16.7, or 30 mmol/l. A first-phase insulin response consistently
      peaked at 1 min, and a slowly ascending second phase occurred at 16.7 and 30
      mmol/l glucose. Glucose-induced insulin secretion in vivo is thus biphasic, with
      a similarly increasing second phase in the mouse as in humans. In vitro, square
      wave stimulation from a baseline of 3 mmol/l glucose induced similar biphasic
      insulin secretion and [Ca(2+)](c) increases, with sustained and flat second
      phases. The glucose dependency (3-30 mmol/l) of both changes was sigmoidal with,
      however, a shift to the right of the relation for insulin secretion compared with
      that for [Ca(2+)](c). The maximum [Ca(2+)](c) increase was achieved by glucose
      concentrations, causing half-maximum insulin secretion. Because this was true for
      both phases, we propose that contrary to current concepts, amplifying signals are
      also implicated in first-phase glucose-induced insulin secretion. To mimic in
      vivo conditions, islets were stimulated with high glucose after being initially
      perifused with 8.5 instead of 3.0 mmol/l glucose. First-phase insulin secretion
      induced by glucose at 11.1, 16.7, and 30 mmol/l was decreased by approximately
      50%, an inhibition that could not be explained by commensurate decreases in
      [Ca(2+)](c) or in the pool of readily releasable granules. Also unexpected was
      the gradually ascending pattern of the second phase, now similar to that in vivo.
      These observations indicated that variations in prestimulatory glucose can
      secondarily affect the magnitude and pattern of subsequent glucose-induced
      insulin secretion.

PMID- 16443780
TI  - Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and
      genetic polymorphisms at its locus (Sgne1).
AB  - C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice
      do not. In this study, we examined whether this differential glucose homeostasis
      was associated with differences of proteolytic activation of pancreatic
      prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin
      between the two strains but a significantly lower glucagon level in B6 mice.
      Pulse-chase analysis of glucagon biosynthesis in isolated pancreatic islets
      revealed that proglucagon was less efficiently processed in B6 mice. Because
      proprotein convertase (PC)2 and its 7B2 helper protein are required for this
      processing, we quantified islet mRNA levels by RT-PCR and protein levels by
      immunoblotting. The levels of proPC2 mRNA were similar between the two strains,
      but B6 protein extracts contained less of the mature PC2. In contrast, 7B2 mRNA
      and protein levels were both significantly lower in B6 pancreas. Sequencing of
      the 7B2 gene promoter and cDNA in the two strains revealed seven single
      nucleotide polymorphisms and one dinucleotide insertion/deletion in the cDNA as
      well as a single nucleotide polymorphism and two insertions/deletions in the
      promoter. Differential expression of 7B2 may contribute to the difference between
      B6 and C3H mice not only in glucagon production and secretion but also in glucose
      tolerance.

PMID- 16443781
TI  - Gestational glucose tolerance and risk of type 2 diabetes in young Pima Indian
      offspring.
AB  - The in utero environment is a powerful risk factor for type 2 diabetes in
      offspring, but little is known about the risk conveyed by nondiabetic gestational
      glucose levels. This issue was explored in 911 nondiabetic Pima Indian mothers
      and 1,436 of their children. Associations were assessed in multivariate models
      between maternal third trimester glucose tolerance and indexes of body
      composition and glycemic control in their children. At parturition, the mothers'
      ages ranged from 14 to 43 years. Offspring were studied at age 0-39 years. An SD
      (1.3 mmol/l) of maternal glucose was associated with 56 g higher birth weight (P
      = 0.0002). This effect persisted when only offspring of normal glucose tolerant
      mothers were examined (57 g, P < 0.0001). In Cox proportional hazards models, the
      adjusted hazard rate ratio for offspring risk of diabetes per SD maternal glucose
      was 1.6 (95% CI 1.3-2.0, P < 0.0001). When only offspring of normal glucose
      tolerant mothers were examined, the risk was reduced but remained significant
      (1.3 [1.04-1.71], P = 0.026). In conclusion, maternal glycemia during pregnancy
      is associated with increased birth weight and risk of diabetes in Pima Indian
      offspring, even when mothers are normal glucose tolerant during pregnancy. Thus,
      prevention of offspring type 2 diabetes may require strategies that focus on
      improving gestational glucose tolerance even within the normal range.

PMID- 16443782
TI  - Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic
      mice.
AB  - Altered cardiac metabolism and function (diabetic cardiomyopathy) has been
      observed in diabetes. We hypothesize that cardiac efficiency, the ratio of
      cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption
      (MVo(2)), is reduced in diabetic hearts. Experiments used ex vivo working hearts
      from control db/+, db/db (type 2 diabetes), and db/+ mice given streptozotocin
      (STZ; type 1 diabetes). PVA and ventricular function were assessed with a 1.4-F
      pressure-volume catheter at low (0.3 mmol/l) and high (1.4 mmol/l) fatty acid
      concentrations with simultaneous measurements of MVo(2). Substrate oxidation and
      mitochondrial respiration were measured in separate experiments. Diabetic hearts
      showed decreased cardiac efficiency, revealed as an 86 and 57% increase in
      unloaded MVo(2) in db/db and STZ-administered hearts, respectively. The slope of
      the PVA-MVo(2) regression line was increased for db/db hearts after elevation of
      fatty acids, suggesting that contractile inefficiency could also contribute to
      the overall reduction in cardiac efficiency. The end-diastolic and end-systolic
      pressure-volume relationships in db/db hearts were shifted to the left with
      elevated end-diastolic pressure, suggesting left ventricular remodeling and/or
      myocardial stiffness. Thus, by means of pressure-volume technology, we have for
      the first time documented decreased cardiac efficiency in diabetic hearts caused
      by oxygen waste for noncontractile purposes.

PMID- 16443783
TI  - Statins prevent dextrose-induced endothelial barrier dysfunction, possibly
      through inhibition of superoxide formation.
AB  - Statins may have favorable effects on endothelial barrier function, possibly
      through reduction of oxidative stress and modulation of expression of vasoactive
      proteins. The permeability of human umbilical endothelial cells in culture to a
      group of fluorescein isothiocyanate dextrans of different molecular weights were
      studied under various experimental conditions. Superoxide anion production was
      measured with an ethidium bromide fluorescence method. Cellular endothelin 1 mRNA
      and endothelin 1 in culture media were measured with Northern blots and enzyme
      immunoassays, respectively. Rosuvastatin (10 nmol/l) normalized the 500 mg/dl
      dextrose-induced permeability changes. Superoxide anion production induced by 500
      mg/dl dextrose was inhibited by therapeutic concentrations of rosuvastatin or
      simvastatin (10 nmol/l), whereas the increased levels of cellular endothelin 1
      mRNA and endothelin 1 in culture media was inhibited by supratherapeutic
      concentrations of statins (> or =0.1 micromol/l). In conclusion, 1) endothelial
      cell barrier dysfunction occurs in cells treated with high concentrations of
      dextrose, 2) statin treatment of endothelial cells normalizes barrier
      permeability, and 3) the favorable effects of statins may be attributed to the
      inhibition of the dextrose-induced increase in superoxide anions, whereas
      inhibition of endothelin expression was observed only at supratherapeutic
      concentrations.

PMID- 16443784
TI  - Loss of endothelial glycocalyx during acute hyperglycemia coincides with
      endothelial dysfunction and coagulation activation in vivo.
AB  - Hyperglycemia is associated with increased susceptibility to atherothrombotic
      stimuli. The glycocalyx, a layer of proteoglycans covering the endothelium, is
      involved in the protective capacity of the vessel wall. We therefore evaluated
      whether hyperglycemia affects the glycocalyx, thereby increasing vascular
      vulnerability. The systemic glycocalyx volume was estimated by comparing the
      distribution volume of a glycocalyx permeable tracer (dextran 40) with that of a
      glycocalyx impermeable tracer (labeled erythrocytes) in 10 healthy male subjects.
      Measurements were performed in random order on five occasions: two control
      measurements, two measurements during normoinsulinemic hyperglycemia with or
      without N-acetylcysteine (NAC) infusion, and one during mannitol infusion.
      Glycocalyx measurements were reproducible (1.7 +/- 0.2 vs. 1.7 +/- 0.3 l).
      Hyperglycemia reduced glycocalyx volume (to 0.8 +/- 0.2 l; P < 0.05), and NAC was
      able to prevent the reduction (1.4 +/- 0.2 l). Mannitol infusion had no effect on
      glycocalyx volume (1.6 +/- 0.1 l). Hyperglycemia resulted in endothelial
      dysfunction, increased plasma hyaluronan levels (from 70 +/- 6 to 112 +/- 16
      ng/ml; P < 0.05) and coagulation activation (prothrombin activation fragment 1 +
      2: from 0.4 +/- 0.1 to 1.1 +/- 0.2 nmol/l; d-dimer: from 0.27 +/- 0.1 to 0.55 +/-
      0.2 g/l; P < 0.05). Taken together, these data indicate a potential role for
      glycocalyx perturbation in mediating vascular dysfunction during hyperglycemia.

PMID- 16443785
TI  - Diabetes enhances mRNA levels of proapoptotic genes and caspase activity, which
      contribute to impaired healing.
AB  - We previously reported that after a bacteria-induced wound in the scalp, type 2
      diabetic (db/db) mice had higher levels of apoptosis of fibroblasts and bone
      lining cells that are critical for healing compared with normoglycemic controls.
      To investigate mechanisms by which this might occur, RNA profiling and caspase
      activity was measured after inoculation of Porphyromonas gingivalis. Diabetes
      caused a more than twofold induction of 71 genes that directly or indirectly
      regulate apoptosis and significantly enhanced caspase-8, -9, and -3 activity. The
      functional significance of diabetes-induced apoptosis was studied by treating
      diabetic mice with a pancaspase inhibitor, z-VAD-fmk (N-benzyloxycarbonyl-Val-Ala
      Asp-fluoromethylketone). Inhibiting apoptosis significantly improved several
      parameters of healing, including fibroblast density, enhanced mRNA levels of
      collagen I and III, and increased matrix formation. Improvements were also noted
      in bone, with an increase in the number of bone-lining cells and new bone
      formation. Thus, diabetes-enhanced apoptosis represents an important mechanism
      through which healing is impaired, and this can be explained, in part, by
      diabetes-increased expression of proapoptotic genes and caspase activity.

PMID- 16443787
TI  - Retinal vessel diameters and risk of impaired fasting glucose or diabetes: the
      Rotterdam study.
AB  - The association between a smaller retinal arteriolar-to-venular ratio (AVR) and
      incident diabetes may be due to arteriolar narrowing, venular dilatation, or
      both. We investigated associations between baseline vessel diameters and incident
      impaired fasting glucose or diabetes in a population-based cohort (aged > or =55
      years). Baseline retinal vessel diameters (1990-1993) were measured on digitized
      images of 2,309 subjects with a normal glucose tolerance test (postload glucose
      <7.8 mmol/l). At follow-up (1997-1999), impaired fasting glucose was defined as
      6.1-7.0 mmol/l and diabetes as > or =7.0 mmol/l and/or antidiabetic medication
      use. Odds ratios (ORs) per SD increase in venular diameters were 1.13 (95% CI
      1.00-1.29) for impaired fasting glucose and 1.09 (0.90-1.33) for diabetes. ORs
      per SD decrease in arteriolar diameters were 1.12 (0.98-1.27) and 1.08 (0.89
      1.31) and per SD decrease in AVR were 1.29 (1.13-1.46) and 1.19 (0.98-1.45).
      After adjustment for cardiovascular risk factors, the associations were unaltered
      for venules and disappeared for arterioles. After stratification on age,
      associations between venular dilatation and impaired fasting glucose (1.23 [1.02
      1.47]) or diabetes (1.18 [0.89-1.56]) were mainly present in participants aged
      <70 years. In conclusion, in our study, the risk of impaired fasting glucose and
      diabetes with AVR was explained by venular dilatation rather than arteriolar
      narrowing, warranting more focus on the causes of this dilatation.

PMID- 16443786
TI  - Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates
      nitric oxide synthesis in vivo by promoting the association of heat shock protein
      90 and endothelial nitric oxide synthase.
AB  - Metformin, one of most commonly used drugs for the treatment of type 2 diabetes,
      improves vascular endothelial functions and reduces cardiovascular events in
      patients with type 2 diabetes, although its mechanisms remain unknown. The
      current study aimed to elucidate how metformin improves endothelial functions.
      Exposure of cultured bovine aortic endothelial cells (BAECs) to clinically
      relevant concentrations of metformin (50-500 micromol/l) dose-dependently
      increased serine-1179 (Ser1179) phosphorylation (equal to human Ser1179) of
      endothelial nitric oxide (NO) synthase (eNOS) as well as its association with
      heat shock protein (hsp)-90, resulting in increased activation of eNOS and NO
      bioactivity (cyclic GMP). These effects of metformin were mimicked or completely
      abrogated by adenoviral overexpression of a constitutively active 5'-AMP
      activated kinase (AMPK) mutant or a kinase-inactive AMPK-alpha, respectively.
      Furthermore, administration of metformin as well as 5-aminoimidazole-4
      carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179
      phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in
      wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that AMPK
      is required for metformin-enhanced eNOS activation in vivo. Finally, incubation
      of BAECs with clinically relevant concentrations of metformin dramatically
      attenuated high-glucose (30 mmol/l)-induced reduction in the association of hsp90
      with eNOS, which resulted in increased NO bioactivity with a reduction in
      overexpression of adhesion molecules and endothelial apoptosis caused by high
      glucose exposure. Taken together, our results indicate that metformin might
      improve vascular endothelial functions in diabetes by increasing AMPK-dependent,
      hsp90-mediated eNOS activation.

PMID- 16443788
TI  - Insulin improves myocardial blood flow in patients with type 2 diabetes and
      coronary artery disease.
AB  - Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until
      now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects
      with coronary artery disease (CAD) has been unknown. We studied the effects of
      insulin on MBF in ischemic regions evaluated by single-photon emission-computed
      tomography and coronary angiography and in nonischemic regions in 43 subjects
      (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was
      measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n =
      43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia
      (n = 26) using positron emission tomography and (15)O-labeled water. MBF was
      significantly attenuated in ischemic regions as compared with in nonischemic
      regions (P < 0.0001) and was increased by insulin as compared with in the fasting
      state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic
      regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine
      infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P
      = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF
      similarly in ischemic and nonischemic regions in type 2 diabetic subjects with
      CAD. Consequently, in addition to its metabolic effects, insulin infusion may
      improve endothelial function and thus increase the threshold for ischemia and
      partly contribute to the beneficial effects found in clinical trials in these
      subjects.

PMID- 16443789
TI  - Effect of pioglitazone on pancreatic beta-cell function and diabetes risk in
      Hispanic women with prior gestational diabetes.
AB  - The Pioglitazone In Prevention Of Diabetes (PIPOD) study was conducted to
      evaluate beta-cell function, insulin resistance, and the incidence of diabetes
      during treatment with pioglitazone in Hispanic women with prior gestational
      diabetes who had completed participation in the Troglitazone In Prevention Of
      Diabetes (TRIPOD) study. Women who completed the TRIPOD study were offered
      participation in the PIPOD study for a planned 3 years of drug treatment and 6
      months of postdrug washout. Oral glucose tolerance tests were performed annually
      on pioglitazone and at the end of the postdrug washout. Intravenous glucose
      tolerance tests (IVGTTs) for assessment of insulin sensitivity and beta-cell
      function were conducted at baseline, after 1 year on pioglitazone, and at the end
      of the postdrug washout. Of 95 women who were not diabetic at the end of the
      TRIPOD study, 89 enrolled in the PIPOD study, 86 completed at least one follow-up
      visit, and 65 completed all study visits, including the postdrug tests.
      Comparison of changes in beta-cell compensation for insulin resistance across the
      TRIPOD and PIPOD studies revealed that pioglitazone stopped the decline in beta
      cell function that occurred during placebo treatment in the TRIPOD study and
      maintained the stability of beta-cell function that had occurred during
      troglitazone treatment in the TRIPOD study. The risk of diabetes, which occurred
      at an average rate of 4.6% per year, was lowest in women with the largest
      reduction in total IVGTT insulin area after 1 year of treatment. The similarity
      of findings between the PIPOD and TRIPOD studies support a class effect of
      thiazolidinedione drugs to enhance insulin sensitivity, reduce insulin secretory
      demands, and preserve pancreatic beta-cell function, all in association with a
      relatively low rate of type 2 diabetes, in Hispanic women with prior gestational
      diabetes.

PMID- 16443790
TI  - Interactions between noncontiguous haplotypes in the adiponectin gene ACDC are
      associated with plasma adiponectin.
AB  - Adiponectin, an adipocyte protein important in insulin sensitization and
      cardioprotection, has a strong genetic component. We hypothesized that variants
      in the adiponectin gene (adipocyte collagen-domain containing [ACDC]) contribute
      to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC
      single nucleotide polymorphisms (SNPs) in 631 non-Hispanic white and 553 African
      American unrelated adolescents in grades 5-12 randomly selected from the
      Princeton School District Study. ACDC SNPs -11,391 (A allele), -10,068 (G
      allele), and +276 (T allele) were associated with higher adiponectin, adjusting
      for sex, puberty stage, BMI Z score, and waist Z score. Contiguous two-SNP
      haplotypes of promoter variants -11,391/-10,068 were significantly associated
      with adiponectin levels in whites and African Americans (P < 0.0001 and 0.03,
      respectively). Extended haplotypes from the promoter through the second intron (
      11,391 to +349) strongly associated with adiponectin in whites (P = 6 x 10(-11))
      and African Americans (P = 0.004), but haplotypes of first intron SNPs -4,521 to 
      657 did not (P > 0.2). Noncontiguous haplotypes or interactions between two-SNP (
      11,391/-10,068) and three-SNP (+45, +276, and +349) haplotypes predicted
      adiponectin better than either region alone. Variants of ACDC are associated with
      adiponectin levels in whites and African Americans. Interactions between
      noncontiguous ACDC haplotypes strongly influence adiponectin levels, suggesting
      nonadditive and potentially cis relationships between these regions.

PMID- 16443791
TI  - Hemostatic markers of endothelial dysfunction and risk of incident type 2
      diabetes: the Framingham Offspring Study.
AB  - Endothelial dysfunction may precede development of type 2 diabetes. We tested the
      hypothesis that elevated levels of hemostatic markers of endothelial dysfunction,
      plasminogen activator inhibitor-1 (PAI-1) antigen, and von Willebrand factor
      (vWF) antigen predicted incident diabetes independent of other diabetes risk
      factors. We followed 2,924 Framingham Offspring subjects (54% women, mean age 54
      years) without diabetes at baseline (defined by treatment, fasting plasma glucose
      > or =7 or 2-h postchallenge glucose > or =11.1 mmol/l) over 7 years for new
      cases of diabetes (treatment or fasting plasma glucose > or =7.0 mmol/l). We used
      a series of regression models to estimate relative risks for diabetes per
      interquartile range (IQR) increase in PAI-1 (IQR 16.8 ng/ml) and vWF (IQR 66.8%
      of control) conditioned on baseline characteristics. Over follow-up, there were
      153 new cases of diabetes. Age- and sex-adjusted relative risks of diabetes were
      1.55 per IQR for PAI-1 (95% CI 1.41-1.70) and 1.49 for vWF (1.21-1.85). These
      effects remained after further adjustment for diabetes risk factors (including
      physical activity; HDL cholesterol, triglyceride, and blood pressure levels;
      smoking; parental history of diabetes; use of alcohol, nonsteroidal anti
      inflammatory drugs, exogenous estrogen, or hypertension therapy; and impaired
      glucose tolerance), waist circumference, homeostasis model assessment of insulin
      resistance, and inflammation (assessed by levels of C-reactive protein): the
      adjusted relative risks were 1.18 per IQR for PAI-1 (1.01-1.37) and 1.39 for vWF
      (1.09-1.77). We conclude that in this community-based sample, plasma markers of
      endothelial dysfunction increased risk of incident diabetes independent of other
      diabetes risk factors including obesity, insulin resistance, and inflammation.

PMID- 16443792
TI  - Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of
      Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1.
AB  - Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), or CD152, is a negative
      regulator of T-cell activation and has been shown to be associated with
      autoimmune diseases. Previous work has demonstrated a defect in the expression of
      this molecule in nonobese diabetic (NOD) mice upon anti-CD3 stimulation in vitro.
      Using a genetic approach we here demonstrate that a novel locus (Ctex) telomeric
      on chromosome 1 together with the Idd3 (Il-2) gene confers optimal CTLA-4
      expression upon CD3 activation of T-cells. Based on these data, we provide a
      model for how gene interaction between Idd3 (IL-2), Ctex, and Idd5.1 (Ctla-4)
      could confer susceptibility to autoimmune diabetes in the NOD mouse.
      Additionally, we showed that the Ctex and the Idd3 regions do not influence
      inducible T-cell costimulator (ICOS) protein expression in NOD mice. Instead, as
      previously shown, higher ICOS levels in NOD mice appear to be controlled by
      gene(s) in the Idd5.1 region, possibly a polymorphism in the Icos gene itself.

PMID- 16443793
TI  - ACDC/adiponectin polymorphisms are associated with severe childhood and adult
      obesity.
AB  - Common single nucleotide polymorphisms (SNPs) in the ACDC adiponectin encoding
      gene have been associated with insulin resistance and type 2 diabetes in several
      populations. Here, we investigate the role of SNPs -11,377C > G, -11,391G > A,
      +45T > G, and +276G > T in 2,579 French Caucasians (1,229 morbidly obese and
      1,350 control subjects). We found an association between severe forms of obesity
      and -11,377C (odds ratio 1.23, P = 0.001) and +276T (1.19, P = 0.006).
      Surprisingly, alternative alleles -11,377G and +276G have been previously
      reported as risk factors for type 2 diabetes. Transmission disequilibrium tests
      showed a trend in overtransmission (56.7%) of a risk haplotype 1((C))-1((G))
      1((T))-2((T)) including -11,377C and +276T in 634 obesity trios (P = 0.097).
      Family-based analysis in 400 trios from the general population indicated
      association between obesity haplotype and higher adiponectin levels, suggesting a
      role of hyperadiponectinemia in weight gain. However, experiments studying the
      putative roles of SNPs -11,377C > G and +276G > T on ACDC functionality were not
      conclusive. In contrast, promoter SNP -11,391G > A was associated with higher
      adiponectin levels in obese children (P = 0.005) and in children from the general
      population (0.00007). In vitro transcriptional assays showed that -11,391A may
      increase ACDC activity. In summary, our study suggests that variations at the
      ACDC/adiponectin gene are associated with risk of severe forms of obesity.
      However, the mechanisms underlying these possible associations are not fully
      understood.

PMID- 16443794
TI  - Quantitative trait loci on chromosome 8q24 for pancreatic beta-cell function and
      7q11 for insulin sensitivity in obese nondiabetic white and black families:
      evidence from genome-wide linkage scans in the NHLBI Hypertension Genetic
      Epidemiology Network (HyperGEN) study.
AB  - Genome-wide linkage scans were carried out using a multipoint variance components
      method in white and black families of the NHLBI Hypertension Genetic Epidemiology
      Network (HyperGEN) study to identify quantitative trait loci (QTLs) for
      pancreatic beta-cell function and insulin sensitivity estimated through the newly
      released nonlinear computer version of homeostasis model assessment 2.
      Participants fasting <8 h, with diagnosed type 2 diabetes, or taking blood
      glucose or blood lipid-lowering medications were excluded. Both phenotypes were
      adjusted separately by race and sex for the effects of age, BMI, and field center
      before linkage scans using 370 microsatellite markers were performed. A total of
      685 white families (1,180 sibpairs) and 773 black families (775 sibpairs) were
      evaluated as well as subsets including 267 obese white families (757 sibpairs)
      and 427 obese black families (599 sibpairs) identified through tree-linkage
      analyses using interacting covariates of age, sex, and BMI. For beta-cell
      function in the obese white families, significant (logarithm of odds [LOD] score
      >3.6) evidence supporting linkages was detected on chromosome 8q24 at D8S1179
      (135 cM, LOD score 4.2, empirical P = 0.002) and at D8S1128 (140 cM, LOD score
      3.7, empirical P = 0.003). In addition, two regions supported linkage for insulin
      sensitivity index in the obese black families on chromosome 7q11 at D7S3046 (79
      cM, LOD score 3.0, empirical P = 0.018) and on chromosome 6q26 at D6S1277 (173
      cM, LOD score 3.0, empirical P = 0.018). Reducing clinical heterogeneity using
      obesity data and improved estimates of beta-cell function and insulin sensitivity
      may have permitted identification of a QTL on chromosome 8q24 for beta-cell
      function in the presence of estimated insulin resistance and a QTL on chromosome
      7q11 for insulin sensitivity. These regions replicate previous reports for type 2
      diabetes-associated traits.

PMID- 16443795
TI  - Analysis of polymorphisms of the interleukin-18 gene in type 1 diabetes and Hardy
      Weinberg equilibrium testing.
AB  - Recently, the interleukin-18 cytokine gene (IL18) was reported to be associated
      with type 1 diabetes. In the present report, we calculated that the reported
      genotypes of the two 5' region/promoter single nucleotide polymorphisms (SNPs), 
      607 (C-->A) (rs1946518) and -137 (G-->C) (rs187238), were not in Hardy-Weinberg
      equilibrium (HWE). We therefore investigated the association of the -607 and -137
      SNPs in a U.K. type 1 diabetic Caucasian case-control collection (1,560 case and
      1,715 control subjects tested at -607 and 4,323 case and 4,610 control subjects
      tested at -137) as well as a type 1 diabetic Caucasian collection comprised of
      families of European ancestry (1,347 families tested at -137 and 1,356 families
      tested at -607). No evidence for association with type 1 diabetes was found,
      including for the -607 A/A and C/A genotypes. To evaluate whether common
      variation elsewhere in the gene was associated with disease susceptibility, we
      analyzed eight IL18 tag SNPs in a type 1 diabetic case-control collection (1,561
      case and 1,721 control subjects). No evidence for association was obtained (P =
      0.11). We conclude that common allelic variation in IL18 is unlikely to
      contribute substantially to type 1 diabetes susceptibility in the populations
      tested and recommend routine application of tests for HWE in population-based
      studies for genetic association.

PMID- 16443796
TI  - Bias in clinical intervention research.
AB  - Research on bias in clinical trials may help identify some of the reasons why
      investigators sometimes reach the wrong conclusions about intervention effects.
      Several quality components for the assessment of bias control have been
      suggested, but although they seem intrinsically valid, empirical evidence is
      needed to evaluate their effects on the extent and direction of bias. This
      narrative review summarizes the findings of methodological studies on the
      influence of bias in clinical trials. A number of methodological studies suggest
      that lack of adequate randomization in published trial reports may be associated
      with more positive estimates of intervention effects. The influence of double
      blinding and follow-up is less clear. Several studies have found a significant
      association between funding sources and pro-industry conclusions. However, the
      methodological studies also show that bias is difficult to detect and appraise.
      The extent of bias in individual trials is unpredictable. A-priori exclusion of
      trials with certain characteristics is not recommended. Appraising bias control
      in individual trials is necessary to avoid making incorrect conclusions about
      intervention effects.

PMID- 16443797
TI  - Cellular phones, cordless phones, and the risks of glioma and meningioma
      (Interphone Study Group, Germany).
AB  - The widespread use of cellular telephones has generated concern about possible
      adverse health effects, particularly brain tumors. In this population-based case
      control study carried out in three regions of Germany, all incident cases of
      glioma and meningioma among patients aged 30-69 years were ascertained during
      2000-2003. Controls matched on age, gender, and region were randomly drawn from
      population registries. In total, 366 glioma cases, 381 meningioma cases, and
      1,494 controls were interviewed. Overall use of a cellular phone was not
      associated with brain tumor risk; the respective odds ratios were 0.98 (95%
      confidence interval (CI): 0.74, 1.29) for glioma and 0.84 (95% CI: 0.62, 1.13)
      for meningioma. Among persons who had used cellular phones for 10 or more years,
      increased risk was found for glioma (odds ratio = 2.20, 95% CI: 0.94, 5.11) but
      not for meningioma (odds ratio = 1.09, 95% CI: 0.35, 3.37). No excess of temporal
      glioma (p = 0.41) or meningioma (p = 0.43) was observed in cellular phone users
      as compared with nonusers. Cordless phone use was not related to either glioma
      risk or meningioma risk. In conclusion, no overall increased risk of glioma or
      meningioma was observed among these cellular phone users; however, for long-term
      cellular phone users, results need to be confirmed before firm conclusions can be
      drawn.

PMID- 16443798
TI  - Coffee consumption and incidence of colorectal cancer in two prospective cohort
      studies of Swedish women and men.
AB  - Investigators have reported an inverse association between coffee consumption and
      risk of colorectal cancer in several case-control studies, but prospective
      studies, most of them involving small numbers of cases, have not supported such a
      relation. In this analysis, the authors prospectively examined the association of
      coffee consumption with colorectal cancer risk among participants from two
      population-based cohort studies: 61,433 women in the Swedish Mammography Cohort
      and 45,306 men in the Cohort of Swedish Men. Information about coffee consumption
      was obtained from food frequency questionnaires in 1987-1990 and 1997 for women
      and in 1997 for men. The authors used Cox proportional hazards modeling for
      cohort-specific multivariate analyses, and results were pooled using random
      effects models. During 1,240,597 person-years of follow-up, 1,279 incident cases
      of colorectal cancer were diagnosed. Coffee consumption was not associated with
      risk of colorectal cancer, colon cancer, or rectal cancer in either women or men.
      For both cohorts combined, the multivariate rate ratio for colorectal cancer for
      each additional cup of coffee per day was 1.00 (95% confidence interval: 0.97,
      1.04). The associations were not modified by colorectal cancer risk factors. The
      findings from these two large prospective cohort studies do not support the
      hypothesis that coffee consumption lowers the risk of colorectal cancer.

PMID- 16443800
TI  - The serum pepsinogen test as a predictor of gastric cancer: the Hisayama study.
AB  - The authors examined whether a serum pepsinogen test (SPT) based on the
      combination of the serum pepsinogen I level and pepsinogen I/II ratio is a good
      predictor of gastric cancer occurrence in a general Japanese population. A total
      of 2,446 subjects aged > or =40 years were classified into negative, positive,
      and strong-positive SPT groups and were followed prospectively for 14 years (1988
      2002). Compared with that for the negative SPT group (26 men, 10 women), gastric
      cancer incidence increased significantly for both men (n = 17; age-adjusted
      hazard ratio = 4.56, 95% confidence interval: 2.42, 8.60) and women (n = 6; age
      adjusted hazard ratio = 5.84, 95% confidence interval: 2.00, 17.11) in the strong
      positive SPT group. It was also significantly higher in the positive SPT group
      for men (n = 23; age-adjusted hazard ratio = 3.91, 95% confidence interval: 2.23,
      6.86). These associations did not attenuate even after adjustment for other
      comprehensive risk factors. Stratified analysis revealed significant associations
      between the SPT and development of intestinal-type gastric cancer as well as of
      cancer in both Helicobacter pylori-negative and -positive subjects. These
      findings suggest that the SPT can serve as a predictor of intestinal-type gastric
      cancer, irrespective of H. pylori infection.

PMID- 16443801
TI  - Racial and ethnic disparities in influenza vaccination coverage among adults
      during the 2004-2005 season.
AB  - During the 2004-2005 influenza season, the supply of vaccine to the United States
      was significantly reduced. In response, the Centers for Disease Control and
      Prevention and the Advisory Committee on Immunization Practices issued interim
      recommendations for prioritizing vaccination. Given trends in racial/ethnic
      disparities in vaccination for influenza, the authors assessed the impact of the
      shortage on those historically less likely to be vaccinated. Using data from the
      Behavioral Risk Factor Surveillance System, they considered vaccination coverage
      among those non-Hispanic Whites, non-Hispanic Blacks, and Hispanics who had
      priority for being vaccinated during the 2004-2005 influenza season. The vaccine
      shortage had a significant negative effect on coverage among adults aged 65 years
      or older across the three racial/ethnic groups. Yet, the magnitude of the
      disparities in coverage did not change significantly from previous seasons. This
      finding may imply similar patterns of vaccine-seeking behavior during shortage
      and nonshortage years. No racial/ethnic differences were seen among adults aged
      18-64 years, which likely reflects the higher percentage of health-care workers
      in this age group. Yearly monitoring of influenza vaccine coverage is important
      to assess the long-term impact of shortages on overall coverage and gaps in
      coverage between racial/ethnic groups.

PMID- 16443802
TI  - Childhood social environment and risk of drug and alcohol abuse in a cohort of
      Danish men born in 1953.
AB  - In a 32-year follow-up study, the authors analyze how social circumstances during
      early life, childhood social participation, and school performance affect the
      risk of being admitted to a hospital or dying from a diagnosis closely related to
      drug or alcohol abuse in young adulthood. A total of 11,376 Danish males born in
      1953, for whom data from birth certificates and conscription board examinations
      had been traced, were followed until 2002 through linkage to the Danish
      Psychiatric, National Patient, and Cause of Death registries. At age 12 years,
      7,877 subjects completed a questionnaire on social participation and school
      performance. During follow-up, 12 percent of these were given a diagnosis
      indicating drug or alcohol abuse. Having a single mother and a working-class
      father were each associated with an increased risk of drug or alcohol abuse in
      adult life. At age 12 years, those who disliked school, scored low on a school
      test, or preferred to visit a youth club during leisure time showed a greater
      risk of adult substance abuse. These associations were slightly attenuated when
      adjusted for educational status at conscription. Deprived social circumstances
      during childhood, poor school performance in early adolescence, and attending a
      youth club seemed to be independent markers of substance abuse in adult life.

PMID- 16443803
TI  - The effect of ozone and PM10 on hospital admissions for pneumonia and chronic
      obstructive pulmonary disease: a national multicity study.
AB  - A case-crossover study was conducted in 36 US cities to evaluate the effect of
      ozone and particulate matter with an aerodynamic diameter of < or =10 microm
      (PM10) on respiratory hospital admissions and to identify which city
      characteristics may explain the heterogeneity in risk estimates. Respiratory
      hospital admissions and air pollution data were obtained for 1986-1999. In a meta
      analysis based on the city-specific regression models, several city
      characteristics were evaluated as effect modifiers. During the warm season, the 2
      day cumulative effect of a 5-ppb increase in ozone was a 0.27% (95% confidence
      interval (CI): 0.08, 0.47) increase in chronic obstructive pulmonary disease
      admissions and a 0.41% (95% CI: 0.26, 0.57) increase in pneumonia admissions.
      Similarly, a 10-microg/m(3) increase in PM10 during the warm season resulted in a
      1.47% (95% CI: 0.93, 2.01) increase in chronic obstructive pulmonary disease at
      lag 1 and a 0.84% (95% CI: 0.50, 1.19) increase in pneumonia at lag 0. Percentage
      of households with central air conditioning reduced the effect of air pollution,
      and variability of summer apparent temperature reduced the effect of ozone on
      chronic obstructive pulmonary disease. The study confirmed, in a large sample of
      cities, that exposure to ozone and PM10 is associated with respiratory hospital
      admissions and provided evidence that the effect of air pollution is modified by
      certain city characteristics.

PMID- 16443804
TI  - Distinguishing the temporal association between women's intravaginal practices
      and risk of human immunodeficiency virus infection: a prospective study of South
      African women.
AB  - Cross-sectional studies have suggested that intravaginal practices, such as
      douching or "dry sex," may increase women's susceptibility to infection with
      human immunodeficiency virus (HIV). The authors examined the temporal nature of
      this association in a cohort of South African women. At enrollment (2001-2002),
      4,089 women were tested for HIV infection. Participants reported their
      intravaginal practices at a 6-month follow-up visit and were followed with repeat
      HIV testing for up to 24 months. Among the 3,570 women who were HIV-negative at
      enrollment, 26% reported some type of intravaginal practice, mostly washing
      inside the vagina with water and/or cloth as part of daily hygiene. During follow
      up, 85 incident HIV infections were observed. Intravaginal practices were
      associated with prevalent HIV at enrollment (adjusted odds ratio = 1.50, 95%
      confidence interval: 1.22, 1.85), but during follow-up there was no association
      between intravaginal practices and incident HIV (adjusted hazard ratio = 1.04,
      95% confidence interval: 0.65, 1.68). These findings may be explained by a
      reversal of the causal sequence assumed for this association, since intravaginal
      practices may be undertaken in response to vaginal infections that occur more
      commonly among HIV-infected women. Intravaginal practices appear unlikely to be a
      cofactor in the male-to-female transmission of HIV in this setting.

PMID- 16443805
TI  - 2005 AHA Guidelines for CPR and ECG: new, but Improved?

PMID- 16443806
TI  - Intra-aortic balloon counterpulsation therapy.

PMID- 16443808
TI  - Use of peripheral venous access devices for obtaining blood samples for
      measurement of activated partial thromboplastin times.

PMID- 16443807
TI  - Update on stress ulcer prophylaxis in critically ill patients.

PMID- 16443809
TI  - Nesiritide: the latest drug for treating heart failure.

PMID- 16443810
TI  - Use of amiodarone to prevent atrial fibrillation after cardiac surgery.

PMID- 16443811
TI  - Dialogue and discourse: are we having the right conversations?

PMID- 16443815
TI  - Ground critical care transport: a lifesaving intervention.

PMID- 16443817
TI  - Patch fluorometry: shedding new light on ion channels.
AB  - Patch fluorometry has emerged as a new approach to the study of the structure
      function relationship in membrane-embedded functional ion channels. Simultaneous
      fluorescent and electrical recordings are achieved from a small number of
      channels in a cell-free membrane patch, yielding high recording sensitivities.
      Further improvement of this approach should permit direct observation of the
      gating motion of a single-channel protein.

PMID- 16443818
TI  - Cryo-EM and single particles.
AB  - Cryoelectronmicroscopy is a method for the imaging of macromolecules in the
      electron microscope. It was originally developed to determine membrane protein
      structures from two-dimensional crystals, but more recently "single-particle"
      techniques have become powerful and popular. Three-dimensional reconstructions
      are obtained from sets of single-particle images by extensive computer
      processing; the methods are being applied to many macromolecular assemblies.

PMID- 16443819
TI  - Strategies for developing therapeutic application of human embryonic stem cells.
AB  - The ongoing debate on human embryonic stem cells (hESC) is fueled by ethical
      concerns but also by the legitimate hope that hESC could one day be used for the
      cure of presently untreatable human diseases. Here we discuss current approaches
      to and constraints upon hESC differentiation and describe their potential
      application in clinical medicine.

PMID- 16443820
TI  - Intrauterine programming of physiological systems: causes and consequences.
AB  - The intrauterine conditions in which the mammalian fetus develops have an
      important role in regulating the function of its physiological systems later in
      life. Changes in the intrauterine availability of nutrients, oxygen, and hormones
      program tissue development and lead to abnormalities in adult cardiovascular and
      metabolic function in several species. The timing, duration, severity, and type
      of insult during development determines the specific physiological outcome.
      Intrauterine programming of physiological systems occurs at the gene, cell,
      tissue, organ, and system levels and causes permanent structural and functional
      changes, which can lead to overt disease, particularly with increasing age.

PMID- 16443821
TI  - Development and regulation of dendritic spine synapses.
AB  - Dendritic spines are small protrusions from neuronal dendrites that form the
      postsynaptic component of most excitatory synapses in the brain. They play
      critical roles in synaptic transmission and plasticity. Recent advances in
      imaging and molecular technologies reveal that spines are complex, dynamic
      structures that contain a dense array of cytoskeletal, transmembrane, and
      scaffolding molecules. Several neurological and psychiatric disorders exhibit
      dendritic spine abnormalities.

PMID- 16443822
TI  - AMPK: a key sensor of fuel and energy status in skeletal muscle.
AB  - Contraction induces marked metabolic changes in muscle, and the AMP-activated
      protein kinase (AMPK) is a good candidate to explain these effects. Recent work
      using a muscle-specific knockout of the upstream kinase, LKB1, has confirmed that
      the LKB1-->AMPK cascade is the signaling pathway responsible for many of these
      effects.

PMID- 16443823
TI  - Ste20-type kinases: evolutionarily conserved regulators of ion transport and cell
      volume.
AB  - Ste20 serine/threonine kinases regulate fundamental cellular processes including
      the cell cycle, apoptosis, and stress responses. Recent studies in Caenorhabditis
      elegans and mammals demonstrate that Ste20 kinases also function in cell volume
      sensing and Cl- transport regulation. Yeast Ste20 initiates a shrinkage activated
      MAPK cascade that regulates organic osmolyte accumulation. Ste20 kinases thus
      play evolutionarily conserved roles in cellular volume sensing and regulation.
      They may also function in systemic osmotic homeostasis and to link cell-cycle
      events with cell volume.

PMID- 16443824
TI  - Calcium-activated potassium channels and the regulation of vascular tone.
AB  - Different calcium signals in the endothelium and smooth muscle target different
      types of Ca2+-sensitive K+ channels to modulate vascular function. These
      differential calcium signals and targets represent multilayered opportunities for
      prevention and/or treatment of vascular dysfunctions.

PMID- 16443825
TI  - Identification of mouse palmitoyl-coenzyme A Delta9-desaturase.
AB  - Stearoyl-coenzyme A desaturase (SCD) catalyzes the desaturation of saturated
      fatty acids to monounsaturated fatty acids in mammalian cells. Currently, there
      are four known enzymatic isoforms (SCD1-SCD4) in the mouse genome. The
      physiological roles for multiple SCD isoforms and their substrate specificities
      are unknown at present. We report here distinct substrate specificities for the
      mouse SCD isoforms. Each SCD isoform was able to complement the ole1 mutation in
      Saccharomyces cerevisiae through heterologous expression of transgenic SCD. Fatty
      acid analysis showed that mouse SCD1, SCD2, and SCD4 desaturate both C18:0 and
      C16:0, whereas mouse SCD3 uses C16:0 but not C18:0. We identify SCD3 as a
      mammalian palmitotyl-CoA Delta9-desaturase, and its existence in mouse helps
      explain distinct physiological roles for each SCD isoform.

PMID- 16443826
TI  - Prediction of the functional class of lipid binding proteins from sequence
      derived properties irrespective of sequence similarity.
AB  - Lipid binding proteins play important roles in signaling, regulation, membrane
      trafficking, immune response, lipid metabolism, and transport. Because of their
      functional and sequence diversity, it is desirable to explore additional methods
      for predicting lipid binding proteins irrespective of sequence similarity. This
      work explores the use of support vector machines (SVMs) as such a method. SVM
      prediction systems are developed using 14,776 lipid binding and 133,441 nonlipid
      binding proteins and are evaluated by an independent set of 6,768 lipid binding
      and 64,761 nonlipid binding proteins. The computed prediction accuracy is 78.9,
      79.5, 82.2, 79.5, 84.4, 76.6, 90.6, 79.0, and 89.9% for lipid degradation, lipid
      metabolism, lipid synthesis, lipid transport, lipid binding, lipopolysaccharide
      biosynthesis, lipoprotein, lipoyl, and all lipid binding proteins, respectively.
      The accuracy for the nonmember proteins of each class is 99.9, 99.2, 99.6, 99.8,
      99.9, 99.8, 98.5, 99.9, and 97.0%, respectively. Comparable accuracies are
      obtained when homologous proteins are considered as one, or by using a different
      SVM kernel function. Our method predicts 86.8% of the 76 lipid binding proteins
      nonhomologous to any protein in the Swiss-Prot database and 89.0% of the 73 known
      lipid binding domains as lipid binding. These findings suggest the usefulness of
      SVMs for facilitating the prediction of lipid binding proteins. Our software can
      be accessed at the SVMProt server (http://jing.cz3.nus.edu.sg/cgi
      bin/svmprot.cgi).

PMID- 16443827
TI  - CpG-C ISS-ODN activation of blood-derived B cells from healthy and chronic
      immunodeficiency virus-infected macaques.
AB  - Cytosine-phosphate-guanine class C (CpG-C) immunostimulatory sequence
      oligodeoxynucleotides (ISS-ODNs) activate human B cells and dendritic cells
      (DCs), properties that suggest potential use as a novel adjuvant to enhance
      vaccine efficacy. After demonstrating that the CpG-C ISS-ODN C274 activates
      macaque DCs, we examined in vitro activation of macaque B cells by C274 as a
      prelude to evaluation of this molecule as an adjuvant in the testing of candidate
      human immunodeficiency virus vaccines in the rhesus macaque-simian
      immunodeficiency virus (SIV) model. C274 induced macaque CD20(+) B cells to
      proliferate more strongly than CD40 ligand or CpG-B ISS-ODN. C274 enhanced B cell
      survival; increased viability was most evident after 3-7 days of culture.
      Increased expression of CD40, CD80, and CD86 by B cells was apparent within 24 h
      of exposure to C274 and persisted for up to 1 week. C274-stimulated, B cell
      enriched and peripheral blood mononuclear cell suspensions from naive and
      immunodeficiency virus-infected monkeys secreted several cytokines [e.g.,
      interleukin (IL)-3, IL-6, IL-12, interferon-alpha] and chemokines [e.g., monocyte
      chemoattractant protein-1/CC chemokine ligand 2 (CCL2), macrophage-inflammatory
      protein-1alpha/CCL3, IL-8/CXC chemokine ligand 8]. In comparison, exposure of
      macaque B cells to SIV had minimal impact on surface phenotype, despite inducing
      cytokine and chemokine production in cells from infected and uninfected animals.
      These observations emphasize the need to identify strategies to optimally boost
      immune function, as immunodeficiency viruses themselves only partially activate B
      cells and DCs. The ability of C274 to stimulate B cells and DCs in healthy and
      infected monkeys suggests its possible use as a broad-acting adjuvant to be
      applied in the rhesus macaque model for the development of preventative and
      therapeutic vaccines.

PMID- 16443829
TI  - Sheep Veterinary Society's concerns about welfare.

PMID- 16443828
TI  - Suppression of MIP-1beta transcription in human T cells is regulated by inducible
      cAMP early repressor (ICER).
AB  - Local production of macrophage inflammatory protein-1beta (MIP-1beta), a beta
      chemokine that blocks human immunodeficiency virus type 1 (HIV-1) entry into CD4+
      CC chemokine receptor 5+ target cells, may be a significant factor in resistance
      to HIV-1 infection and control of local viral spread. The mechanisms governing
      MIP-1beta expression in T cells, however, are not well understood. Our results
      suggest that MIP-1beta RNA expression in T cells is dynamically regulated by
      transcriptional factors of the cyclic adenosine monophosphate (cAMP) responsive
      element (CRE)-binding (CREB)/modulator family. Transient transfection of primary
      human T cells with 5' deletion and site-specific mutants of the human MIP-1beta
      promoter identified an activated protein-1 (AP-1)/CRE-like motif at position -74
      to -65 base pairs, relative to the TATA box as a vital cis-acting element and a
      binding site for inducible cAMP early repressor (ICER). Ectopic expression of
      ICER or induction of endogenous ICER with the cAMP agonists forskolin and
      prostaglandin E2 resulted in the formation of ICER-containing complexes,
      including an ICER:CREB heterodimer to the AP-1/CRE-like site and inhibition of
      MIP-1beta promoter activity. Our data characterize an important binding site for
      the dominant-negative regulator ICER in the MIP-1beta promoter and suggest that
      dynamic changes in the relative levels of ICER and CREB play a crucial role in
      cAMP-mediated attenuation of MIP-1beta transcription in human T cells.

PMID- 16443833
TI  - EU adopts animal welfare action plan.

PMID- 16443835
TI  - Call for immediate test of avian flu contingency plans.

PMID- 16443836
TI  - Patterns and significance of bite wounds in Eurasian otters (Lutra lutra) in
      southern and south-west England.
AB  - Postmortem examinations were carried out on 379 otters found dead in southern and
      south-west England between 1988 and 2003. Most (81 per cent) were road
      casualties, but many had open bite wounds and in some cases these had proved
      fatal. Mortality was strongly seasonal and was positively correlated with night
      length. Although numbers decreased in the summer months, the prevalence of bite
      wounds in adults was highest in late summer. The number of otters examined
      annually and the prevalence of bite wounds increased markedly during the study
      period, and in 2003 more than half the otters of both sexes had recent bite
      wounds. The majority of the bites were considered to have been caused by other
      otters, but some were thought to have been inflicted by American mink (Mustela
      vison). Bites to cubs were mostly caused by domestic dogs. The overall mortality
      due to bite wounds was approximately 10 per cent.

PMID- 16443837
TI  - Transient erythropoietic protoporphyria associated with chronic hepatitis and
      cirrhosis in a cohort of German shepherd dogs.
AB  - Over the course of one year, slight jaundice and ascites suggestive of chronic
      liver disease occurred in 17 German shepherd dogs from one breeding colony. Blood
      analyses, performed twice with a six-month interval, revealed elevated serum
      activities of liver enzymes in 13 dogs. In addition, four young adult German
      shepherd dogs that showed severe ascites, slight jaundice and increased serum
      liver enzyme activities were referred for further evaluation. Because of their
      poor prognosis these four dogs were euthanased. There were no signs of
      photosensitivity. Postmortem examinations revealed macronodular darkened livers,
      which were characterised histopathologically by cirrhosis associated with
      aggregates of brown pigments showing a striking orange birefringence in polarised
      light. Ultrastructurally, the crystalline pigments were typical of
      protoporphyrins. High-performance liquid chromatographic analysis of liver
      samples revealed very high levels of protoporphyrins (mean 9550 nmol/g wet liver,
      reference value 0.41 nmol/g wet liver) and low activities of ferrochelatase (mean
      0.274 mmol/mg protein/hour, reference value 0.684 nmol/mg protein/hour). Twenty
      six months after the onset of the hepatopathies, the clinical condition of the 13
      surviving dogs had improved and their serum liver enzyme activities were normal.
      The clinical histories and pedigree analyses were not in concordance with an
      inherited form of protoporphyria. There was no known history of exposure to toxic
      substances or drugs. The findings are in accordance with a transient
      erythropoietic protoporphyria associated with hepatic complications, presumably
      caused by exposure to a porphyrinogenic, ferrochelatase-inhibitory substance of
      unknown origin.

PMID- 16443838
TI  - Echocardiographic and Doppler echocardiographic findings in 11 wolves (Canis
      lupus).
AB  - Two-dimensional real-time, M-mode and Doppler echocardiographic measurements were
      made in 11 adult wolves (Canis lupus) anaesthetised with an intramuscular
      combination of medetomidine, ketamine, butorphanol and acepromazine followed by
      isoflurane in oxygen. M-mode measurements of the left ventricle, B-mode
      measurements of the left atrium and aorta, systolic indices, and Doppler
      measurements of aortic and pulmonary blood outflow, and of mitral and tricuspid
      blood inflow, were recorded. The values obtained were compared with those
      reported for dogs of similar bodyweight and body type. The diastolic measurements
      of the cardiac chambers and walls were similar to those reported for healthy,
      conscious dogs, but the use of anaesthesia probably resulted in the markedly
      different systolic cardiac measurements, systolic indices and Doppler blood flow
      velocities observed in the wolves. Mild mitral regurgitation, probably due to
      mitral endocardiosis, was observed in one wolf, and trivial functional mitral
      insufficiency was observed in five others.

PMID- 16443839
TI  - Spatial distribution of Culicoides imicola, the main vector of bluetongue virus,
      in Spain.

PMID- 16443840
TI  - Datura stramonium poisoning in horses: a risk factor for colic.

PMID- 16443841
TI  - First autochthonous case of canine ocular Dirofilaria repens infection in
      Germany.

PMID- 16443844
TI  - Ethical issues in the provision of veterinary services.

PMID- 16443846
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16443847
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16443851
TI  - Stem cell technology in equine tendon and ligament injuries.

PMID- 16443849
TI  - Cutaneous blastomycosis in a cat.

PMID- 16443852
TI  - Badger culling and bovine TB.

PMID- 16443853
TI  - Is the E133K allele of VG5Q associated with Klippel-Trenaunay and other
      overgrowth syndromes?
AB  - BACKGROUND: It has been reported that the activating mutation, E133K, in the
      angiogenic factor VG5Q (formally named AGGF1) causes Klippel-Trenaunay Syndrome
      (KTS), a rare vascular disease associated with asymmetric overgrowth. This
      proposal followed from the observation that five out of 130 KTS patients were
      constitutionally heterozygous for VG5Q, E133K. OBJECTIVE: To explore the
      possibility that VG5Q, and specifically E133K, is implicated in other mosaic
      overgrowth syndromes. RESULTS: 24 patients were analysed for this sequence
      change. One patient was constitutionally heterozygous for E133K. Analysis of both
      parents revealed that the patient's mother, who was healthy, also carried E133K.
      An analysis of 275 healthy controls showed that 3.3% (9/275) of the population
      were carriers of E133K. CONCLUSIONS: The findings bring into question the
      assertion that VG5Q, E133K is a mutation and that it causes KTS.

PMID- 16443854
TI  - Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43
      cases.
AB  - BACKGROUND: Costello syndrome (CS) is a rare multiple congenital abnormality
      syndrome, associated with failure to thrive and developmental delay. One of the
      more distinctive features in childhood is the development of facial warts, often
      nasolabial and in other moist body surfaces. Individuals with CS have an
      increased risk of malignancy, suggested to be about 17%. Recently, mutations in
      the HRAS gene on chromosome 11p13.3 have been found to cause CS. METHODS: We
      report here the results of HRAS analysis in 43 individuals with a clinical
      diagnosis of CS. RESULTS: Mutations were found in 37 (86%) of patients. Analysis
      of parental DNA samples was possible in 16 cases for both parents and in three
      cases for one parent, and confirmed the mutations as de novo in all of these
      cases. Three novel mutations (G12C, G12E, and K117R) were found in five cases.
      CONCLUSIONS: These results confirm that CS is caused, in most cases, by
      heterozygous missense mutations in the proto-oncogene HRAS. Analysis of the major
      phenotypic features by mutation suggests a potential correlation between
      malignancy risk and genotype, which is highest for patients with an uncommon
      (G12A) substitution. These results confirm that mutation testing for HRAS is a
      reliable diagnostic test for CS.

PMID- 16443855
TI  - Mutations of the RET gene in isolated and syndromic Hirschsprung's disease in
      human disclose major and modifier alleles at a single locus.
AB  - BACKGROUND: In Hirschsprung's disease (HSCR), a hypomorphic allele of a major
      gene, RET, accounts for most isolated (non-syndromic) cases, along with other
      autosomal susceptibility loci under a multiplicative model. However, some
      syndromic forms of HSCR are monogenic entities, for which the disease causing
      gene is known. OBJECTIVE: To determine whether RET could be considered a modifier
      gene for the enteric phenotype on the background of a monogenic trait. METHODS:
      The syndromic HSCR entities studied were congenital central hypoventilation
      (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene
      mutations, respectively. The RET locus was genotyped in 143 CCHS patients, among
      whom 44 had HSCR, and in 30 MWS patients, among whom 20 had HSCR. The
      distribution of alleles, genotypes, and haplotypes was compared within the
      different groups. To test the interaction in vivo, heterozygous mice were bred
      for a null allele of Phox2b and Ret genes. RESULTS: RET was shown to act as a
      modifier gene for the HSCR phenotype in patients with CCHS but not with MWS. The
      intestine of double heterozygote mice was indistinguishable from their
      littermates. A loss of over 50% of each gene function seemed necessary in the
      mouse model for an enteric phenotype to occur. CONCLUSIONS: In CCHS patients, the
      weak predisposing haplotype of the RET gene can be regarded as a quantitative
      trait, being a risk factor for the HSCR phenotype, while in MWS, for which the
      HSCR penetrance is high, the role of the RET predisposing haplotype is not
      significant. It seems likely that there are both RET dependent and RET
      independent HSCR cases.

PMID- 16443856
TI  - The sepiapterin reductase gene region reveals association in the PARK3 locus:
      analysis of familial and sporadic Parkinson's disease in European populations.
AB  - BACKGROUND: Parkinson's disease is a genetically complex disease with mixed mode
      of inheritance. Recently, a haplotype across the sepiapterin reductase (SPR)
      gene, which is located in the PARK3 linkage region, was shown to modulate age of
      onset of Parkinson's disease in sibships from North America. OBJECTIVE: To make a
      thorough assessment of the SPR gene region in sporadic Parkinson's disease.
      METHODS: A linkage study in 122 European sibship families with five
      microsatellite and 17 single nucleotide polymorphism (SNP) markers in and around
      the SPR gene region, and an association analysis in 340 sporadic cases of
      Parkinson's disease and 680 control subjects from Germany with 40 SNPs. Linkage
      was evaluated by non-parametric linkage scores and genotypic or haplotype
      association was tested by regression analysis, assuming different risk effect
      models. RESULTS: Significant LOD scores between 2 and 3 were obtained at the two
      SPR-flanking markers D2S2110 and D2S1394 and seven SNP markers around the SPR
      gene. We found the previously reported promoter SNP rs1876487 also significantly
      associated with age of onset in our sib pair families (p-value 0.02). One strong
      linkage disequilibrium (LD) block of 45 kb including the entire SPR gene was
      observed. Within this LD block all 14 inter-correlated SNPs were significantly
      associated with Parkinson's disease affection status (p-value 0.004).
      CONCLUSIONS: DNA polymorphisms in a highly intercorrelated LD block, which
      includes the SPR gene, appear to be associated with both sporadic and familial
      Parkinson's disease. This confirms a previous study showing that SPR potentially
      modulates the onset of or risk for Parkinson's disease.

PMID- 16443857
TI  - Subpopulation difference scanning: a strategy for exclusion mapping of
      susceptibility genes.
AB  - BACKGROUND: Association mapping is a common strategy for finding disease-related
      genes in complex disorders. Different association study designs exist, such as
      case-control studies or admixture mapping. METHODS: We propose a strategy,
      subpopulation difference scanning (SDS), to exclude large fractions of the genome
      as locations of genes for complex disorders. This strategy is applicable to genes
      explaining disease incidence differences within founder populations, for example,
      in cardiovascular diseases in Finland. RESULTS: The strategy consists of
      genotyping a set of markers from unrelated individuals sampled from
      subpopulations with differing disease incidence but otherwise as similar as
      possible. When comparing allele or haplotype frequencies between the
      subpopulations, the genomic areas with little difference can be excluded as
      possible locations for genes causing the difference in incidence, and other areas
      therefore targeted with case-control studies. As tests of this strategy, we use
      real and simulated data to show that under realistic assumptions of population
      history and disease risk parameters, the strategy saves efforts of sampling and
      genotyping and most efficiently detects genes of low risk--that is, those most
      difficult to find with other strategies. CONCLUSION: In contrast to admixture
      mapping that uses the mixing of two different populations, the SDS strategy takes
      advantage of drift within highly related subpopulations.

PMID- 16443858
TI  - Improved prandial glucose control with lower risk of hypoglycemia with
      nateglinide than with glibenclamide in patients with maturity-onset diabetes of
      the young type 3.
AB  - OBJECTIVE: To study the effect of the short-acting insulin secretagogue
      nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3),
      which is characterized by a defective insulin response to glucose and
      hypersensitivity to sulfonylureas. RESEARCH DESIGN AND METHODS: We compared the
      acute effect of nateglinide, glibenclamide, and placebo on prandial plasma
      glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with
      MODY3. After an overnight fast, they received on three randomized occasions
      placebo, 1.25 mg glibenclamide, or 30 mg nateglinide before a standard 450-kcal
      test meal and light bicycle exercise for 30 min starting 140 min after the
      ingestion of the first test drug. RESULTS: Insulin peaked earlier after
      nateglinide than after glibenclamide or placebo (median [interquartile range]
      time 70 [50] vs. 110 [20] vs. 110 [30] min, P = 0.0002 and P = 0.0025,
      respectively). Consequently, compared with glibenclamide and placebo, the peak
      plasma glucose (P = 0.031 and P < 0.0001) and incremental glucose areas under
      curve during the first 140 min of the test (P = 0.041 and P < 0.0001) remained
      lower after nateglinide. The improved prandial glucose control with nateglinide
      was achieved with a lower peak insulin concentration than after glibenclamide
      (47.0 [26.0] vs. 80.4 [71.7] mU/l; P = 0.023). Exercise did not induce
      hypoglycemia after nateglinide or placebo, but after glibenclamide six patients
      experienced symptomatic hypoglycemia and three had to interrupt the test.
      CONCLUSIONS: A low dose of nateglinide prevents the acute postprandial rise in
      glucose more efficiently than glibenclamide and with less stimulation of peak
      insulin concentrations and less hypoglycemic symptoms.

PMID- 16443859
TI  - Additive beneficial effects of fenofibrate combined with candesartan in the
      treatment of hypertriglyceridemic hypertensive patients.
AB  - OBJECTIVE: Mechanisms underlying fibric acid and angiotensin II type 1 receptor
      blocker therapies differ. Signaling from peroxisome proliferator-activated
      receptor alpha may cross-talk with the angiotensin II system. We investigated
      vascular and metabolic responses to these therapies either alone or in
      combination in hypertriglyceridemic hypertensive patients. RESEARCH DESIGN AND
      METHODS: This was a randomized, double-blind, placebo-controlled, cross-over
      trial with three treatment arms (each 2 months) and two washout periods (each 2
      months). Forty-four patients were given 200 mg fenofibrate and placebo, 200 mg
      fenofibrate and 16 mg candesartan, or 16 mg candesartan and placebo daily during
      each treatment period. RESULTS: Fenofibrate, combined therapy, or candesartan
      therapy significantly reduced blood pressure. However, combined therapy
      significantly reduced blood pressure more than fenofibrate or candesartan alone
      (P < 0.001 by ANOVA). When compared with candesartan, fenofibrate or combined
      therapy significantly improved the lipoprotein profile. All three treatment arms
      significantly improved flow-mediated dilator response to hyperemia. Combined
      therapy significantly decreased plasma malondialdehyde, high-sensitivity C
      reactive protein, and soluble CD40L levels relative to baseline measurements.
      Importantly, these parameters were changed to a greater extent with combined
      therapy when compared with monotherapy (P < 0.001, P = 0.002, P = 0.050, and P =
      0.032 by ANOVA, respectively). Fenofibrate, combined therapy, and candesartan
      significantly increased plasma adiponectin levels and insulin sensitivity
      relative to baseline measurements. However, the magnitude of these increases were
      not significantly different among the three therapies (P = 0.246 and P = 0.153 by
      ANOVA, respectively). CONCLUSIONS: Fenofibrate combined with candesartan improves
      endothelial function and reduces inflammatory markers to a greater extent than
      monotherapy in hypertriglyceridemic hypertensive patients.

PMID- 16443860
TI  - Effects of intravenous nicorandil before reperfusion for acute myocardial
      infarction in patients with stress hyperglycemia.
AB  - OBJECTIVE: Stress hyperglycemia increases the risk of mortality and poor outcomes
      in patients with acute myocardial infarction (AMI). We aimed to assess effects of
      intravenous nicorandil administered before reperfusion on AMI patients with
      stress hyperglycemia. RESEARCH DESIGN AND METHODS: This study consisted of 158
      consecutive first AMI patients with stress hyperglycemia who underwent
      percutaneous coronary intervention (PCI) within 24 h from the onset. They were
      randomly assigned to receive 12 mg of nicorandil (n = 81) or a placebo (n = 77)
      intravenously just before reperfusion. Stress hyperglycemia was defined as a
      blood glucose level > or =10 mmol/l (180 mg/dl). We examined various aspects of
      epicardial flow and microvascular function as immediate data and major adverse
      cardiac events (MACEs) (coronary heart disease death or unplanned readmission due
      to congestive heart failure) as late-phase data. RESULTS: The incidence of slow
      flow after PCI was lower in the nicorandil group (13.6 vs. 27.3%, P < 0.04). ST
      segment resolution >50% was observed in 70.4 and 53.2% on nicorandil and placebo,
      respectively (P < 0.03). Patients treated with nicorandil had a lower peak
      creatine kinase level (3,137 +/- 2,577 vs. 4,333 +/- 3,608, P < 0.02). Upon
      Kaplan-Meier analysis, 5 years' freedom from MACEs was 86.4% in the nicorandil
      group and 74.0% in the placebo (P < 0.05). CONCLUSIONS: Adjunctive therapy with
      administration of intravenous nicorandil before reperfusion on AMI patients with
      stress hyperglycemia significantly improves epicardial flow and prevents the
      occurrence of severe microvascular reperfusion injury, resulting in better
      outcomes in these patients.

PMID- 16443861
TI  - Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation
      in diabetic women.
AB  - OBJECTIVE: To evaluate the dietary predictors for the markers of systemic
      inflammation and endothelial dysfunction in patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: We examined whether intakes of whole grains and
      dietary fiber were associated with inflammatory indicators among 902 diabetic
      women in the Nurses' Health Study. RESULTS: After adjustment for age, BMI,
      lifestyle, and dietary covariates, intakes of whole grains and bran were both
      associated with significantly decreasing trends of C-reactive protein (CRP) (P
      for trend = 0.03 and 0.007, respectively) and tumor necrosis factor-alpha
      receptor 2 (TNF-R2) (P for trend = 0.017 and 0.06). High intake of cereal fiber
      was also inversely associated with the lower levels of CRP (P for trend = 0.03)
      and TNF-R2 (P for trend = 0.01). The concentrations of CRP and TNF-R2 were 18 and
      8% lower in the highest quintile of cereal fiber as compared with the lowest
      quintile. Dietary glycemic index was positively associated with CRP (P for trend
      = 0.04) and TNF-R2 (P for trend = 0.0008) levels. The concentrations of CRP and
      TNF-R2 were 32 and 11% higher, respectively, in the highest quintile of dietary
      glycemic index as compared with the lowest quintile. CONCLUSIONS: Our data
      indicate that whole grains and a low-glycemic index diet may reduce systemic
      inflammation among women with type 2 diabetes.

PMID- 16443862
TI  - Presence of diabetes risk factors in a large U.S. eighth-grade cohort.
AB  - OBJECTIVE: The study was conducted in 12 middle schools to determine the
      prevalence of diabetes, pre-diabetes, and diabetes risk factors in eighth-grade
      students who were predominantly minority and evaluate the feasibility of
      collecting physical and laboratory data in schools. RESEARCH DESIGN AND METHODS:
      Anthropometric measurements and fasting and 2-h post-glucose load blood draws
      were obtained from approximately 1,740 eighth-grade students. RESULTS: Mean
      recruitment rate was 50% per school, 49% had BMI > or = 85th percentile, 40.5%
      had fasting glucose > or = 100 mg/dl, 0.4% had fasting glucose > or = 126 mg/dl,
      and 2.0% had 2-h glucose > or = 140 mg/dl and 0.1% > or = 200 mg/dl. Mean fasting
      insulin value was 30.1 microU/ml, 36.2% had fasting insulin > or = 30 microU/ml,
      and 2-h mean insulin was 102.1 microU/ml. Fasting and 2-h glucose and insulin
      values increased across BMI percentiles, and fasting glucose was highest in
      Hispanic and Native American students. CONCLUSIONS: There was a high prevalence
      of risk factors for diabetes, including impaired fasting glucose (> or =100
      mg/dl), hyperinsulinism suggestive of insulin resistance (fasting insulin > or =
      30 microU/ml), and BMI > or = 85th percentile. These data suggest that middle
      schools are appropriate targets for population-based efforts to decrease
      overweight and diabetes risk.

PMID- 16443863
TI  - Spectrum and prevalence of atherogenic risk factors in 27,358 children,
      adolescents, and young adults with type 1 diabetes: cross-sectional data from the
      German diabetes documentation and quality management system (DPV).
AB  - OBJECTIVE: The aim of this data analysis was to ascertain the type and prevalence
      rate as well as age and sex distribution of cardiovascular risk factors in type 1
      diabetic patients up to 26 years of age. RESEARCH DESIGN AND METHODS:
      Cardiovascular risk factors such as obesity, hypertension, dyslipidemia, poor
      glycemic control, and smoking were analyzed in 27,358 patients who were divided
      into three groups (prepubertal, pubertal, and adult) using specifically designed
      diabetes software for prospective disease documentation. RESULTS: More than half
      of the patients per age-group had at least one cardiovascular risk factor. Two
      risk factors were age dependently found in 6.2-21.7% and three or four risk
      factors in 0.5-4.7%. Elevated values of HbA(1c), total cholesterol, and BMI were
      found most frequently. Hypertension, smoking, and HDL cholesterol were observed
      more frequently in males, and elevated BMI, total cholesterol, and LDL
      cholesterol more often in females. Although 28.6% of the patients had
      dyslipidemia, merely 0.4% of them received medical treatment, and of the 8.1% of
      the patients with hypertension, only 2.1% of them were given antihypertensive
      medication. CONCLUSIONS: With increasing age, a greater number of patients with
      cardiovascular risk factors were observed. Significant sex differences were seen
      in the majority of risk factors. Despite the high prevalence of risk factors,
      only a small minority of patients received antihypertensive or lipid-lowering
      treatment. Early identification, prevention, and treatment of additional risk
      factors seem to be necessary, particularly in light of the high incidence of
      future cardiovascular disease.

PMID- 16443864
TI  - Prevalence of diabetes and impaired fasting glucose in Korea: Korean National
      Health and Nutrition Survey 2001.
AB  - OBJECTIVE: The purpose of this study was to estimate the prevalence of diabetes
      and impaired fasting glucose (IFG) and their association with risk factors in the
      Korean population. RESEARCH DESIGN AND METHODS: The Korean National Health and
      Nutrition Survey 2001 was a nationally representative survey with a stratified
      multistage sampling design. Data from a comprehensive questionnaire, a physical
      examination, and blood tests were obtained from 5,844 Korean adults (2,513 men
      and 3,331 women) aged >20 years. RESULTS: The age-adjusted prevalence of diabetes
      in this Korean population was 7.6%, and the age-adjusted prevalences of
      previously diagnosed diabetes and newly diagnosed diabetes were 4.4 and 3.3%,
      respectively (fasting plasma glucose > or = 7.0 mmol/l). Overall, these results
      indicate that 8.1% or 1.4 million Korean men and 7.5% or 1.3 million Korean women
      have diabetes. The age-adjusted prevalence of IFG was 23.9%, using the new
      American Diabetes Association criteria (fasting plasma glucose 5.6-6.9 mmol/l).
      Diabetes prevalence increased with age and peaked in the oldest age-group;
      however, IFG prevalence did not show the same trend. Diabetes was found to be
      associated with age, BMI, blood pressure, triglyceride, HDL cholesterol,
      education levels, alcohol consumption, exercise, and a family history of
      diabetes. CONCLUSIONS: This study shows that diabetes and IFG are common in
      Korea, and about one-half of diabetes cases remain undiagnosed. These results
      emphasize the need to develop an urgent public program to improve the detection,
      prevention, and treatment of diabetes.

PMID- 16443865
TI  - Trends in deliveries, prenatal care, and obstetrical complications in women with
      pregestational diabetes: a population-based study in Ontario, Canada, 1996-2001.
AB  - OBJECTIVE: To describe recent trends in the proportion of deliveries in women
      with pregestational diabetes (PGD), their use of services, and diabetes-related
      obstetrical complications. RESEARCH DESIGN AND METHODS: In this population-based
      retrospective cohort study, comprehensive administrative data were used to
      identify all women (with and without PGD) who gave birth in an Ontario, Canada,
      hospital from 1996 to 2001. Data on maternal complications and interventions were
      obtained from hospital discharge records; data on use of prenatal services were
      obtained from fee-for-service claims. RESULTS: The proportion of deliveries in
      women with PGD increased steadily from 0.8% in 1996 to 1.2% in 2001 (P < 0.001).
      In 2001, women with PGD were more likely to be diagnosed with shoulder dystocia
      (adjusted odds ratio 2.00 [95% CI 1.55-2.58]), hypertension (4.13 [3.44-4.96]),
      and preeclampsia/eclampsia (4.44 [3.43-5.73]) and have higher rates of inductions
      (1.69 [1.52-1.88]) and caesarean sections (1.78 [1.60-1.98]) than women without
      PGD. In 2001, 50% of the women with PGD had a visit to a diabetes specialist
      during pregnancy and only 30% of women had claims for a prenatal retinal
      examination. Both of these rates have decreased over the study period.
      CONCLUSIONS: Women with PGD now account for a larger proportion of deliveries.
      These women continue to have higher obstetrical complication and intervention
      rates than women without PGD and many do not receive recommended specialty care
      during pregnancy.

PMID- 16443866
TI  - Understanding exercise beliefs and behaviors in women with gestational diabetes
      mellitus.
AB  - OBJECTIVE: The purpose of this study was to examine the exercise beliefs and
      behaviors of postpartum women who had gestational diabetes mellitus (GDM) during
      a recent pregnancy. RESEARCH DESIGN AND METHODS: Postpartum women with GDM (n =
      28) completed a mail survey assessing their self-reported exercise beliefs
      (advantages, barriers, and important social influences) and behaviors. RESULTS:
      We found that 1) the strongest perceived advantage of exercise during pregnancy
      was controlling blood glucose and postpartum it was controlling weight, 2) the
      most common barrier to exercise during pregnancy was fatigue and postpartum it
      was a lack of time, 3) women's husband/partner most strongly influenced their
      exercise during pregnancy and postpartum, 4) women exercised more during the
      postpartum period than before or during pregnancy, and 5) the number of exercise
      advantages was positively associated with women's pregnancy and postpartum
      exercise behavior. CONCLUSIONS: To increase exercise behavior and reduce the risk
      of type 2 diabetes in women with GDM, researchers and health care professionals
      are encouraged to use women's exercise beliefs, that is, advantages, social
      influences, and perceived barriers to exercise, as a framework for designing
      effective diabetes treatment and prevention programs.

PMID- 16443867
TI  - Comparison of weighted performance measurement and dichotomous thresholds for
      glycemic control in the Veterans Health Administration.
AB  - OBJECTIVE: Quality measures of glycemic control using threshold values do not
      assess incremental quality improvement. We compared health care system
      performance using weighted continuous versus dichotomous measures for glycemic
      control. RESEARCH DESIGN AND METHODS: We performed retrospective cross-sectional
      analysis of chart abstraction data on 37,142 diabetic patients from 141 Veterans
      Health Administration medical centers in 2000-2001. RESULTS: Subjects per
      facility ranged from 163 to 740 (mean 263). Mean overall HbA(1c) (A1C) was 7.58%.
      A continuous measure for glycemic control was calculated based on percentage of
      maximal quality-adjusted life-years saved (QALYsS). Overall mean facility
      performance using the dichotomous measure was 62% <8% A1C (range 48-75%) and 39%
      <7% A1C (21-57%), in comparison with 45% maximal QALYsS (31-60%). Correlation
      between QALYsS and A1C thresholds of <8 (0.848) and <7 (0.838) for facility
      rankings was excellent; correlation between facility level performance using
      thresholds of <8 and 7% was poor (r = 0.13, P = 0.14). Comparison of facility
      rankings between the <7% dichotomous measure and the QALYsS-weighted measure
      showed that 22% changed their ranking by > or =2 deciles with marked changes in
      top and bottom deciles. CONCLUSIONS: Facility rankings vary by threshold or
      continuous methodology. However, because significant numbers of individuals are
      unable to reach "optimal" target goals (thresholds) even in clinical trials with
      extensive exclusion criteria, we propose that a continuous measure assessing
      improvement toward optimal A1C, rather than a pass/fail optimal target, is both a
      fairer assessment clinical practice and a more accurate reflection of population
      health improvement.

PMID- 16443868
TI  - Diabetes reporting as a cause of death: results from the Translating Research
      Into Action for Diabetes (TRIAD) study.
AB  - OBJECTIVE: To determine the frequency of reporting of diabetes on death
      certificates of decedents with known diabetes, define factors associated with
      reporting of diabetes, and describe trends in reporting over time. RESEARCH
      DESIGN AND METHODS: Data were obtained from 11,927 participants with diabetes who
      were enrolled in the Translating Research Into Action for Diabetes study, a
      multicenter prospective observational study of diabetes care in managed care.
      Data on decedents (n = 540) were obtained from the National Death Index. The
      primary dependent variable was the presence of ICD-10 codes for diabetes on the
      death certificate. Covariates included age at death, sex, race/ethnicity,
      education, income, duration of diabetes, type of diabetes, diabetes treatment,
      smoking status, and number of comorbidities. RESULTS: Diabetes was recorded on
      39% of death certificates and as the underlying cause of death for 10% of
      decedents with diabetes. Diabetes was significantly less likely to be reported on
      the death certificates of decedents with diabetes dying of cancer. Predictors of
      recording diabetes anywhere on the death certificate included longer duration of
      diabetes and insulin treatment. Longer duration of diabetes, insulin treatment,
      and fewer comorbidities were associated with recording of diabetes as the
      underlying cause of death. CONCLUSIONS: Diabetes is much more likely to be
      reported on the death certificates of diabetic individuals who die of
      cardiovascular causes. Reporting of diabetes on death certificates has been
      stable over time. Death certificates underestimate the prevalence of diabetes
      among decedents and present a biased picture of the causes of death among people
      with diabetes.

PMID- 16443869
TI  - Increased cancer-related mortality for patients with type 2 diabetes who use
      sulfonylureas or insulin.
AB  - OBJECTIVE: Numerous studies have identified an increased risk of cancer in type 2
      diabetes. We explored the association between antidiabetic therapies and cancer
      related mortality in patients with type 2 diabetes, postulating that agents that
      increase insulin levels might promote cancer. RESEARCH DESIGN AND METHODS: This
      was a population-based cohort study using administrative databases from
      Saskatchewan Health. Cancer-related mortality was compared among inception
      cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox
      regression was used to estimate the hazard ratio (HR) of cancer-related
      mortality, after adjusting for age, sex, insulin use, and chronic disease score.
      All statistical tests were two-sided. RESULTS: We identified 10,309 new users of
      metformin or sulfonylureas with an average follow-up of 5.4 +/- 1.9 years (means
      +/- SD). The mean age for the cohort was 63.4 +/- 13.3 years, and 55% were men.
      Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea
      monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of
      1,443) for subjects who used insulin. After multivariate adjustment, the
      sulfonylurea cohort had greater cancer-related mortality compared with the
      metformin cohort (adjusted HR 1.3 [95% CI 1.1-1.6]; P = 0.012). Insulin use was
      associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5
      2.4; P < 0.0001). CONCLUSIONS: Patients with type 2 diabetes exposed to
      sulfonylureas and exogenous insulin had a significantly increased risk of cancer
      related mortality compared with patients exposed to metformin. It is uncertain
      whether this increased risk is related to a deleterious effect of sulfonylurea
      and insulin or a protective effect of metformin or due to some unmeasured effect
      related to both choice of therapy and cancer risk.

PMID- 16443871
TI  - Cost-effectiveness and net benefit of enhanced treatment of depression for older
      adults with diabetes and depression.
AB  - OBJECTIVE: To determine the incremental cost-effectiveness and net benefit of a
      depression collaborative care program compared with usual care for patients with
      diabetes and depression. RESEARCH DESIGN AND METHODS: This article describes a
      preplanned subgroup analysis of patients with diabetes from the Improving Mood
      Promoting Access to Collaborative (IMPACT) randomized controlled trial. The
      setting for the study included 18 primary care clinics from eight health care
      organizations in five states. A total of 418 of 1,801 patients randomized to the
      IMPACT intervention (n = 204) versus usual care (n = 214) had coexisting
      diabetes. A depression care manager offered education, behavioral activation, and
      a choice of problem-solving treatment or support of antidepressant management by
      the primary care physician. The main outcomes were incremental cost-effectiveness
      and net benefit of the program compared with usual care. RESULTS: Relative to
      usual care, intervention patients experienced 115 (95% CI 72-159) more depression
      free days over 24 months. Total outpatient costs were 25 dollars (95% CI -1,638
      to 1,689) higher during this same period. The incremental cost per depression
      free day was 25 cents (-14 dollars to 15 dollars) and the incremental cost per
      quality-adjusted life year ranged from 198 dollars (144-316) to 397 dollars (287
      641). An incremental net benefit of 1,129 dollars (692-1,572) was found.
      CONCLUSIONS: The IMPACT intervention is a high-value investment for older adults
      with diabetes; it is associated with high clinical benefits at no greater cost
      than usual care.

PMID- 16443870
TI  - The impact of patient preferences on the cost-effectiveness of intensive glucose
      control in older patients with new-onset diabetes.
AB  - OBJECTIVE: Cost-effectiveness analyses have reported that intensive glucose
      control is not cost-effective in older patients with new-onset diabetes. However,
      these analyses have had limited data on patient preferences concerning diabetic
      health states. We examined how the cost- effectiveness of intensive glucose
      control changes with the incorporation of patient preferences. RESEARCH DESIGN
      AND METHODS: We collected health state preferences/utilities from 519 older
      diabetic patients. We incorporated these utilities into an established cost
      effectiveness model of intensive glucose control and compared incremental cost
      effectiveness analyses ratios (ICERs) (cost divided by quality-adjusted life-year
      [QALY]) when using the original and patient-derived utilities for complications
      and treatments. RESULTS: The mean utilities were approximately 0.40 for major
      complications, 0.76 (95% CI 0.74-0.78) for conventional glucose control, 0.77
      (0.75-0.80) for intensive therapy with oral medications, and 0.64 (0.61-0.67) for
      intensive therapy with insulin. Incorporating our patient-derived complication
      utilities alone improved ICERs for intensive glucose control (e.g., patients aged
      60-65 years at diagnosis, 136,000 dollars/QALY-->78,000 dollars/QALY), but
      intensive therapy was still not cost-effective at older ages. When patient
      derived treatment utilities were also incorporated, the cost-effectiveness of
      intensive treatment depended on the method of glucose control. Intensive control
      with insulin generated fewer QALYs than conventional control. However, intensive
      control with oral medications was beneficial on average at all ages and had an
      ICER < or =100,000 dollars to age 70. CONCLUSIONS: The cost-effectiveness of
      intensive glucose control in older patients with new-onset diabetes is highly
      sensitive to assumptions regarding quality of life with treatments. Cost
      effectiveness analyses of diabetes care should consider the sensitivity of
      results to alternative utility assumptions.

PMID- 16443872
TI  - Multicentric, randomized, controlled trial to evaluate blood glucose control by
      the model predictive control algorithm versus routine glucose management
      protocols in intensive care unit patients.
AB  - OBJECTIVE: To evaluate a fully automated algorithm for the establishment of tight
      glycemic control in critically ill patients and to compare the results with
      different routine glucose management protocols of three intensive care units
      (ICUs) across Europe (Graz, Prague, and London). RESEARCH DESIGN AND METHODS:
      Sixty patients undergoing cardiac surgery (age 67 +/- 9 years, BMI 27.7 +/- 4.9
      kg/m2, 17 women) with postsurgery blood glucose levels >120 mg/dl (6.7 mmol/l)
      were investigated in three different ICUs (20 per center). Patients were
      randomized to either blood glucose management (target range 80-110 mg/dl [4.4-6.1
      mmol/l]) by the fully automated model predictive control (MPC) algorithm (n = 30,
      10 per center) or implemented routine glucose management protocols (n = 30, 10
      per center). In all patients, arterial glucose was measured hourly to describe
      the glucose profile until the end of the ICU stay but for a maximum period of 48
      h. RESULTS: Compared with routine protocols, MPC treatment resulted in a
      significantly higher percentage of time within the target glycemic range (%
      median [min-max]: 52 [17-92] vs. 19 [0-71]) over 0-24 h (P < 0.01). Improved
      glycemic control with MPC treatment was confirmed in patients remaining in the
      ICU for 48 h (0-24 h: 50 [17-71] vs. 21 [4-67], P < 0.05, and 24-48 h: 65 [38-96]
      vs. 25 [8-79], P < 0.05, for MPC [n = 16] vs. routine protocol [n = 13],
      respectively). Two hypoglycemic events (<54 mg/dl [3.0 mmol/l]) were observed
      with routine protocol treatment. No hypoglycemic event occurred with MPC.
      CONCLUSIONS: The data suggest that the MPC algorithm is safe and effective in
      controlling glycemia in critically ill postsurgery patients.

PMID- 16443873
TI  - The effect of smoking cessation and subsequent resumption on absorption of
      inhaled insulin.
AB  - OBJECTIVE: To assess the absorption profile of inhaled insulin in healthy,
      actively smoking subjects at baseline, after smoking cessation, and after smoking
      resumption and compare it with nonsmoking subjects. RESEARCH DESIGN AND METHODS:
      Insulin pharmacokinetics and glucodynamics were measured in 20 male smoking
      subjects (10-20 cigarettes/day) and 10 matched nonsmoking subjects after
      receiving inhaled insulin (1 mg) or the approximate subcutaneous insulin
      equivalent (3 units) in a randomized cross-over fashion. All smokers then
      received inhaled insulin 12 h, 3 days, and 7 days into a smoking cessation
      period. They then resumed smoking for 2-3 days before again receiving inhaled
      insulin 1 h after the last cigarette. RESULTS: Before smoking cessation, maximum
      insulin concentration (Cmax) and area under the curve (AUC) for insulin
      concentration time (AUC-Insulin(0-360)) with inhaled insulin were higher, and
      time to Cmax (t(max)) shorter, in smokers than nonsmokers (Cmax 26.8 vs. 9.7
      microU/ml; AUC-Insulin(0-360) 2,583 vs. 1,645 microU x ml(-1) x min(-1); t(max)
      20 vs. 53 min, respectively; all P < 0.05), whereas with subcutaneous insulin,
      systemic exposure was unchanged (AUC-Insulin(0-360) 2,324 vs. 2,269 microU x ml(
      1) x min(-1); P = NS). After smoking cessation, AUC-Insulin(0-360) decreased with
      inhaled insulin by up to 50% within 1 week and approached nonsmoker levels. Cmax
      decreased and t(max) increased relative to baseline but were still not comparable
      with nonsmoker values. Smoking resumption completely reversed the effect of
      smoking cessation. Glucodynamics corroborated the observed findings in insulin
      pharmacokinetics. CONCLUSIONS: Cessation and resumption of smoking greatly
      altered the pharmacokinetics of inhaled insulin. As rapid changes in systemic
      insulin exposure increase hypoglycemia risk, inhaled insulin should not be used
      in people with diabetes who choose to continue smoking. This is consistent with
      recommendations that people with diabetes refrain from smoking altogether.

PMID- 16443874
TI  - Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes.
AB  - OBJECTIVE: Telomeres are DNA sequences necessary for DNA replication, which
      shorten at cell division at a rate related to levels of oxidative stress. Once
      shortened to a critical length, cells are triggered into replicative senescence.
      Type 2 diabetes is associated with oxidative DNA damage, and we hypothesized that
      telomere shortening would characterize type 2 diabetes. RESEARCH DESIGN AND
      METHODS: We studied 21 male type 2 diabetic subjects (mean age 61.2 years, mean
      HbA(1c) 7.9%) selected to limit confounding effects on telomere length and 29
      matched control subjects. Telomere length was measured in peripheral venous
      monocyte and T-cells (naive and memory) by fluorescent in situ hybridization and
      oxidative DNA damage by flow cytometry of oxidized DNA bases. Peripheral insulin
      resistance (homeostasis model assessment) and high-sensitivity C-reactive protein
      (hsCRP) were measured. RESULTS: Mean monocyte telomere length in the diabetic
      group was highly significantly lower than in control subjects (4.0 [1.1] vs. 5.5
      [1.1]; P < 0.0001), without significant differences in lymphocyte telomere
      length. There was a trend toward increased oxidative DNA damage in all diabetes
      cell types examined and a significant inverse relationship between oxidative DNA
      damage and telomere length (r = -0.55; P = 0.018) in the diabetic group. Telomere
      length was unrelated to plasma CRP concentration or insulin resistance.
      CONCLUSIONS: Monocyte telomere shortening in type 2 diabetes could be due to
      increased oxidative DNA damage to monocyte precursors during cell division. This
      data suggests that monocytes adhering to vascular endothelium and entering the
      vessel wall in type 2 diabetes are from a population with shorter telomeres and
      at increased risk of replicative senescence within vascular plaque.

PMID- 16443875
TI  - Testing the accelerator hypothesis: body size, beta-cell function, and age at
      onset of type 1 (autoimmune) diabetes.
AB  - OBJECTIVE: The "accelerator hypothesis" predicts that fatness is associated with
      an earlier age at onset of type 1 diabetes. We tested the hypothesis using data
      from the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS:
      Subjects were 449 youth aged <20 years at diagnosis who had positive results for
      diabetes antibodies measured 3-12 months after diagnosis (mean 7.6 months). The
      relationships between age at diagnosis and fatness were examined using BMI as
      measured at the SEARCH visit and reported birth weight, both expressed as SD
      scores (SDSs). RESULTS: Univariately, BMI SDS was not related to age at
      diagnosis. In multiple linear regression, adjusted for potential confounders, a
      significant interaction was found between BMI SDS and fasting C-peptide (FCP) on
      onset age (P < 0.0001). This interaction remained unchanged after additionally
      controlling for number and titers of diabetes antibodies. An inverse association
      between BMI and age at diagnosis was present only among subjects with FCP levels
      below the median (<0.5 ng/ml) (regression coefficient -7.9, P = 0.003). A
      decrease of 1 SDS in birth weight (639 g) was also associated with an
      approximately 5-month earlier age at diagnosis (P = 0.008), independent of sex,
      race/ethnicity, current BMI, FCP, and number of diabetes antibodies. CONCLUSIONS:
      Increasing BMI is associated with younger age at diagnosis of type 1 diabetes
      only among those U.S. youth with reduced beta-cell function. The intrauterine
      environment may also be an important determinant of age at onset of type 1
      diabetes.

PMID- 16443876
TI  - Periodontal changes in children and adolescents with diabetes: a case-control
      study.
AB  - OBJECTIVE: To evaluate the level of oral disease in children and adolescents with
      diabetes. RESEARCH DESIGN AND METHODS: Dental caries and periodontal disease were
      clinically assessed in 182 children and adolescents (6-18 years of age) with
      diabetes and 160 nondiabetic control subjects. RESULTS: There were no differences
      between case and control subjects with respect to dental caries. Children with
      diabetes had significantly higher plaque and gingival inflammation levels
      compared with control subjects. The number of teeth with evidence of attachment
      loss (the hallmark of periodontal disease) was significantly greater in children
      with diabetes (5.79 +/- 5.34 vs. 1.53 +/- 3.05 in control subjects, unadjusted P
      < 0.001). When controlling for age, sex, ethnicity, gingival bleeding, and
      frequency of dental visits, diabetes remained a highly significant correlate of
      periodontitis, especially in the 12- to 18-year-old subgroup. In the case group,
      BMI was significantly correlated with destruction of connective tissue attachment
      and bone, but duration of diabetes and mean HbA(1c) were not. CONCLUSIONS: Our
      findings suggest that periodontal destruction can start very early in life in
      diabetes and becomes more prominent as children become adolescents. Programs
      designed to promote periodontal disease prevention and treatment should be
      provided to young patients with diabetes.

PMID- 16443877
TI  - Altered D-chiro-inositol urinary clearance in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: Evidence suggests that some actions of insulin are effected by
      inositolphosphoglycan (IPG) mediators. We hypothesize that a deficiency in D
      chiro-inositol (DCI) and/or a DCI-containing IPG (DCI-IPG) may contribute to
      insulin resistance in humans. RESEARCH DESIGN AND METHODS: To assess this
      possibility in polycystic ovary syndrome (PCOS), we determined insulin
      sensitivity (Si by frequently sampled intravenous glucose tolerance test), plasma
      and urinary DCI and myo-inositol (MYO) levels (by gas chromatography/mass
      spectrometry), and the release of insulin and DCI-IPG during the oral glucose
      tolerance test (area under the curve [AUC]) in 23 women with PCOS and 26 normal
      women. RESULTS: Women with PCOS were heavier than control subjects (P = 0.002 for
      BMI), but also had decreased Si (P < 0.001) and increased AUC(insulin) (P <
      0.001) compared with normal women, even when corrected for BMI. The urinary
      clearance of DCI (uCl(DCI)) was increased almost sixfold in PCOS compared with
      normal women (P = 0.001), but not MYO clearance (P = 0.10). uCl(DCI) correlated
      inversely with Si when all women were analyzed together (n = 49, r = -0.50, P <
      0.001) and was one of the three best independent parameters predicting Si.
      Finally, the ratio of AUC(DCI-IPG) to AUC(insulin) was decreased threefold in
      women with PCOS (P < 0.001). CONCLUSIONS: uCl(DCI) is inversely correlated with
      insulin sensitivity in women and is a strong independent predictor of insulin
      resistance in multivariate models. PCOS, which is characterized by insulin
      resistance, is associated with a selective increase in uCl(DCI) and impaired DCI
      IPG release in response to insulin. These findings are consistent with a defect
      in tissue availability or utilization of DCI in PCOS that may contribute to the
      insulin resistance of the syndrome.

PMID- 16443879
TI  - Sexual function and endocrine profile in fertile women with type 1 diabetes.
AB  - OBJECTIVE: Aims of this study were 1) to assess sexual function and endocrine
      profile among fertile type 1 diabetic women during the follicular and luteal
      phases of the menstrual cycle, 2) to compare these results with those obtained
      among healthy fertile women who served as control subjects, and 3) to explore the
      correlations between sexual function and endocrine milieu among patients and
      control subjects during the follicular and luteal phases of the menstrual cycle.
      RESEARCH DESIGN AND METHODS: Fifty fertile women with type 1 diabetes and 47
      healthy control subjects completed a semistructured medical interview and filled
      in self-administered validated instruments to evaluate sexual function,
      depression, and sexual distress. Venous blood samples were drawn to measure
      glycated hemoglobin and an endocrine profile during either the follicular or the
      luteal phase of the menstrual cycle. RESULTS: Type 1 diabetic women had decreased
      sexual function and increased sexual distress compared with control subjects
      during the luteal, but not the follicular, phase of the menstrual cycle. During
      the follicular phase, patients had lower estrogenic basal tone, lower "weak"
      androgen (namely Delta4-androstenedione and dehydroepiandrosterone sulfate)
      production, and lower free-triiodothyronine and free-thyroxine levels compared
      with control subjects. During the luteal phase, total testosterone levels were
      higher in patients than control subjects, while 17beta-estradiol and progesterone
      levels were lower in patients than control subjects. CONCLUSIONS: Among type 1
      diabetic women, sexual function and sexual distress vary according to the phase
      of the menstrual cycle. This finding may have implications on the clinical
      assessment of sexual function in type 1 diabetic women.

PMID- 16443878
TI  - Middle-aged premenopausal women with type 1 diabetes have lower bone mineral
      density and calcaneal quantitative ultrasound than nondiabetic women.
AB  - OBJECTIVE: To determine whether middle-aged premenopausal women with type 1
      diabetes had more self-reported fractures and lower bone mineral density (BMD)
      compared with nondiabetic women. RESEARCH DESIGN AND METHODS: Participants were
      premenopausal women aged 35-55 years with type 1 diabetes (n = 67; 32.2 +/- 5.3
      years duration) and without diabetes (n = 237). Total hip, femoral neck, whole
      body, and spine BMD were measured by dual X-ray absorptiometry. Calcaneal
      broadband ultrasound attenuation (BUA) was assessed with quantitative ultrasound.
      RESULTS: Women with type 1 diabetes were more likely to report a fracture after
      age 20 years compared with nondiabetic women (33.3 vs. 22.6%; age-adjusted odds
      ratio 1.89 [95% CI 1.02-3.49]). Type 1 diabetes was associated with lower total
      hip BMD (0.890 vs. 0.961 g/cm2; P < 0.001), femoral neck BMD (0.797 vs. 0.847
      g/cm2; P = 0.001), whole-body BMD (1.132 vs. 1.165 g/cm2; P < 0.01), and lower
      calcaneal BUA (71.6 vs. 84.9 dB/MHz; P < 0.001) after multivariate adjustment.
      BMD was 3-8% lower in type 1 diabetic compared with control women and calcaneal
      BUA was 15% lower. Spine BMD and biomarkers of bone remodeling were not
      significantly different between groups. In the type 1 diabetic women, reduced
      monofilament detection and blindness were both associated with lower BMD.
      CONCLUSIONS: Lower BMD in premenopausal women with type 1 diabetes may
      substantially increase their risk of developing osteoporosis after menopause.
      Type 1 diabetic women should be targeted for osteoporosis screening and possible
      fracture prevention as they transition through menopause.

PMID- 16443880
TI  - Serum lipids and the progression of nephropathy in type 1 diabetes.
AB  - OBJECTIVE: Dyslipidemia contributes to the progression of microvascular disease
      in diabetes. However, different lipid variables may be important at different
      stages of nephropathy. This study examines the pattern of dyslipidemia associated
      with the progression of nephropathy in patients with type 1 diabetes. RESEARCH
      DESIGN AND METHODS: A total of 152 patients with type 1 diabetes were recruited
      in order to represent various phases of nephropathy. Patients were followed for 8
      9 years, during which time they received standard care. Renal progression was
      defined a priori as a doubling in albumin excretion (in patients with normo- or
      microalbuminuria) or a decline in creatinine clearance (in those with
      macroalbuminuria). A panel of lipid variables was determined and correlated with
      indexes of progression. RESULTS: In patients with normoalbuminuria (n = 66),
      progression was associated with male sex (P < 0.05), borderline albuminuria (P =
      0.02), and LDL-free cholesterol (P = 0.02). In patients with microalbuminuria (n
      = 51), progression was independently associated with triglyceride content of VLDL
      and intermediate-density lipoprotein (both P < 0.05). In patients with
      macroalbuminuria (n = 36), a significant decline in the renal function (>3 ml x
      min(-1) x year(-1)) was independently associated with poor glycemic control,
      hypertension, and LDL size (P < 0.05). When all patients with progressive
      nephropathy were analyzed together, only LDL cholesterol was predictive on
      multivariate analysis (P < 0.05), which masked the importance of triglyceride
      enrichment in microalbuminuria. CONCLUSIONS: Lipid variables are associated with
      progression of diabetic kidney disease, but the relationship is not the same at
      all stages. This finding has implications for the design of renoprotective
      strategies and the interpretation of clinical trials in type 1 diabetes.

PMID- 16443881
TI  - Albumin and fibrinogen synthesis and insulin effect in type 2 diabetic patients
      with normoalbuminuria.
AB  - OBJECTIVE: Insulin stimulates albumin synthesis but inhibits that of fibrinogen
      in both type 1 diabetic and healthy subjects. In type 2 diabetes, fibrinogen
      production is increased both in the postabsorptive state and in response to
      hyperinsulinemia. No data exist on the rate of albumin synthesis and its response
      to insulin in type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured
      fractional synthesis rates (FSRs) and absolute synthesis rates (ASRs) of both
      albumin and fibrinogen in postabsorptive normoalbuminuric type 2 diabetic
      patients at their spontaneous glucose levels (study A), as well as albumin FSR
      and ASR before and after a hyperinsulinemic-euglycemic euaminoacidemic clamp
      (study B), using leucine isotope methods. RESULTS: In postabsorptive type 2
      diabetes (study A), albumin FSR (11.2 +/- 0.9%/day) and albumin ASR (15.4 +/- 1.2
      g/day) were not different from control values (albumin FSR: 9.4 +/- 0.7%/day;
      albumin ASR: 13.8 +/- 1.2 g/day, P > 0.1 for both). In contrast, in the type 2
      diabetic subjects, both fibrinogen FSR (24.9 +/- 2.1%/day) and ASR (2.4 +/- 0.2
      g/day) were greater (P < 0.025 and P < 0.007, respectively) compared with the
      control subjects (FSR: 18.6 +/- 1.51%/day; ASR: 1.6 +/- 0.2 g/day). Worse
      metabolic control in the type 2 diabetic patients was associated with
      hyperfibrinogenemia and increased leucine rate of appearance, whereas neither the
      (increased) fibrinogen ASR nor the (normal) albumin production was affected. In
      study B, after hyperinsulinemia (raised to approximately 860 nmol/l), albumin FSR
      and ASR increased by approximately 25% versus basal (P < 0.04) and to the same
      extent in both type 2 diabetic and control subjects. CONCLUSIONS: In
      normoalbuminuric type 2 diabetic patients, postabsorptive albumin synthesis and
      its response to insulin were normal, whereas fibrinogen synthesis was increased,
      irrespective of metabolic control. Furthermore, in normoalbuminuric type 2
      diabetic patients, a normal insulin sensitivity with respect to albumin
      production but a selective hepatic dysregulation of fibrinogen metabolism were
      present.

PMID- 16443882
TI  - High-sensitivity C-reactive protein and coronary heart disease mortality in
      patients with type 2 diabetes: a 7-year follow-up study.
AB  - OBJECTIVE: To investigate in a follow-up study whether high-sensitivity C
      reactive protein (hs-CRP) predicts coronary heart disease (CHD) events in
      subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: The original study
      population consisted of 1,059 patients with type 2 diabetes (age 45-64 years).
      Mean duration of diabetes was 8 years. CRP values were available from 1,045
      subjects, of whom 878 were free of myocardial infarction (MI) at baseline. CHD
      mortality and the incidence of nonfatal MI were assessed in a 7-year follow-up.
      RESULTS: Altogether, 157 patients died from CHD and 254 had a nonfatal or fatal
      CHD event. Patients with hs-CRP >3 mg/l had a higher risk for CHD death than
      patients with hs-CRP < or =3 mg/l (19.8 and 12.9%, respectively, P = 0.004). In
      Cox regression analysis, patients with high hs-CRP had a relative risk of 1.72
      for CHD death even after the adjustment for confounding factors (P = 0.002).
      Among subjects who were free from MI at baseline, those with a high hs-CRP level
      had relative risks of 1.83 (P = 0.003) and 1.84 (P = 0.004) for CHD death in
      univariate and multivariate analyses, respectively. CONCLUSIONS: In this large
      cohort of type 2 diabetic patients, hs-CRP was an independent risk factor for CHD
      deaths.

PMID- 16443883
TI  - Cardiac autonomic neuropathy predicts cardiovascular morbidity and mortality in
      type 1 diabetic patients with diabetic nephropathy.
AB  - OBJECTIVE: Cardiac autonomic neuropathy (CAN) has been associated with a poor
      prognosis in patients with diabetes. Because CAN is common in patients with
      diabetic nephropathy, we evaluated the predictive value of CAN in type 1 diabetic
      patients with and without diabetic nephropathy. RESEARCH DESIGN AND METHODS: In a
      prospective observational follow-up study, 197 type 1 diabetic patients with
      diabetic nephropathy and a matched group of 191 patients with long-standing type
      1 diabetes and normoalbuminuria were followed for 10.1 years (range 0.0-10.3
      years). At baseline, CAN was assessed by heart rate variation (HRV) during deep
      breathing. HRV was evaluated as a predictor of the primary end point:
      cardiovascular morbidity and mortality. As secondary end points, all-cause
      mortality and the influence of HRV on progression of diabetic nephropathy
      (decline in glomerular filtration rate [GFR]) was evaluated. RESULTS: During the
      follow-up, 79 patients (40%) with nephropathy reached the combined primary end
      point vs. 19 patients (10%) with normoalbuminuria (log-rank test, P < 0.0001).
      The unadjusted hazard ratio (HR) for reaching the primary end point when having
      an abnormal HRV (< or =10 bpm) measured at baseline compared with a normal HRV
      was 7.7 (range 1.9-31.5; P = 0.004) in patients with nephropathy. Similarly in
      the normoalbuminuric patients, the unadjusted HR was 4.4 (1.4-13.6; P = 0.009).
      In patients with nephropathy, abnormal HRV was significantly associated with
      fatal and nonfatal cardiovascular disease after adjustment for cardiovascular
      risk factors. The adjusted HR for reaching the primary end point in a patient
      with nephropathy and an abnormal HRV was 6.4 (1.5-26.3, P = 0.010), as compared
      with a normal HRV. The unadjusted HR for dying when having an abnormal HRV
      compared with a normal HRV was 3.3 (95% CI 1.0-10.7; P = 0.043) in patients with
      diabetic nephropathy. After adjustment for confounding factors, the impact of HRV
      on all-cause mortality in patients with nephropathy was no longer significant (P
      = 0.293). There was no relationship between abnormal HRV and rate of decline in
      GFR. CONCLUSIONS: HRV is an independent risk factor for cardiovascular morbidity
      and mortality in type 1 diabetic patients with nephropathy.

PMID- 16443884
TI  - Neuropathy among the diabetes control and complications trial cohort 8 years
      after trial completion.
AB  - OBJECTIVE: To evaluate the impact of prior intensive diabetes therapy on
      neuropathy among former Diabetes Control and Complications Trial (DCCT)
      participants. RESEARCH DESIGN AND METHODS: At the conclusion of the DCCT,
      subjects in the intensive group were encouraged to maintain intensive therapy,
      and subjects in the conventional group were encouraged to begin intensive
      therapy. Thereafter, we annually assessed neuropathy as part of the Epidemiology
      of Diabetes Intervention and Complications (EDIC) study. Neuropathy was defined
      using the Michigan Neuropathy Screening Instrument (MNSI). We recorded potential
      adverse consequences of neuropathy. RESULTS: At the first EDIC examination, 1,257
      subjects participated in the neuropathy assessment. Consistent with DCCT results,
      the former intensive group showed a lower prevalence of neuropathy than the
      conventional group based on positive questionnaire (1.8 vs. 4.7%; P = 0.003) or
      examination (17.8 vs. 28.0%; P < 0.0001) results. Despite similar levels of
      glycemic control, symptoms and signs of neuropathy remained less prevalent among
      the former intensive group compared with the conventional group. At the beginning
      of the EDIC study, prior intensive therapy reduced the odds of having symptoms
      and signs of neuropathy using MNSI criteria by 64% (P = 0.0044) and 45% (P <
      0.0001), respectively, with similar odds reductions observed for both neuropathic
      symptoms (51%, P < 0.0001) and neuropathic signs (43%, P < 0.0001) across 8 years
      of EDIC follow-up. CONCLUSIONS: The benefits of 6.5 years of intensive therapy on
      neuropathy status extended for at least 8 years beyond the end of the DCCT,
      similar to the findings described for diabetic retinopathy and nephropathy.

PMID- 16443885
TI  - Improving metabolic control leads to better working memory in adults with type 2
      diabetes.
AB  - OBJECTIVE: The goals of this study were to determine whether improvements in
      metabolic control can ameliorate the cognitive dysfunction associated with type 2
      diabetes and evaluate the possibility that such improvements are mediated by
      changes in circulating insulin or insulin resistance. RESEARCH DESIGN AND
      METHODS: This randomized double-blind trial enrolled 145 subjects at 18 centers
      in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy
      received add-on therapy with either rosiglitazone, a thiazolidinedione insulin
      sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24
      using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test,
      and the Cambridge Neuropsychological Test Automated Battery. RESULTS:
      Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after
      24 weeks both treatment groups showed similar significant reductions in FPG (2.1
      2.3 mmol/l). Working memory improved with both rosiglitazone (P < 0.001) and
      glyburide (P = 0.017). Improvement (25-31% reduction in errors) was most evident
      on the Paired Associates Learning Test and was significantly correlated (r =
      0.30) with improved glycemic control as measured by FPG. CONCLUSIONS: Similar and
      statistically significant cognitive improvement was observed with both
      rosiglitazone and glyburide therapy, and the magnitude of this effect was
      correlated with the degree to which FPG improved. These results suggest that a
      cognitive benefit is achievable with pharmacological interventions targeting
      glycemic control.

PMID- 16443886
TI  - Mean blood glucose and biological variation have greater influence on HbA1c
      levels than glucose instability: an analysis of data from the Diabetes Control
      and Complications Trial.
AB  - OBJECTIVE: Mean blood glucose (MBG) over 2-3 months is a strong predictor of
      HbA(1c) (A1C) levels. Glucose instability, the variability of blood glucose
      levels comprising the MBG, and biological variation in A1C (BV) have also been
      suggested as predictors of A1C independent of MBG. To assess the relative
      importance of MBG, BV, and glucose instability on A1C, we analyzed patient data
      from the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND
      METHODS: A glucose profile set and sample for A1C were collected quarterly over
      the course of the DCCT from each participant (n = 1,441). The glucose profile set
      consisted of seven samples, one each drawn before and 90 min after breakfast,
      lunch, and dinner and one before bedtime. MBG and glucose instability (SD of
      blood glucose [SDBG]) were calculated as the arithmetic mean and SD of glucose
      profile set samples for each visit, respectively. A statistical model was
      developed to predict A1C from MBG, SDBG, and BV, adjusted for diabetes duration,
      sex, treatment group, stratum, and race. RESULTS: Data from 32,977 visits were
      available. The overall model was highly statistically significant (log likelihood
      = -41,818.75, likelihood ratio chi2[7] = 7,218.71, P > chi2 = 0.0000). MBG and BV
      had large influences on A1C based on their standardized coefficients. SDBG had
      only 1/14 of the impact of MBG and 1/10 of the impact of BV. CONCLUSIONS: MBG and
      BV have a large influence on A1C, whereas SDBG is relatively unimportant.
      Consideration of BV as well as MBG in the interpretation of A1C may enhance our
      ability to monitor diabetes management and predict complications.

PMID- 16443887
TI  - Impact of differences in fasting glucose and glucose tolerance on the hyperbolic
      relationship between insulin sensitivity and insulin responses.
AB  - OBJECTIVE: To determine whether the hyperbolic relationship between insulin
      sensitivity and the acute insulin response to glucose (AIRg) exists in subjects
      with impaired fasting glucose (IFG) or decreased glucose tolerance. RESEARCH
      DESIGN AND METHODS: We studied 219 healthy subjects (88 male and 131 female
      subjects, aged 26-75 years) with fasting plasma glucose (FPG) <6.11 mmol/l.
      Subjects underwent an intravenous glucose tolerance test to determine the insulin
      sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the
      latter a measure of intravenous glucose tolerance. RESULTS: Si and AIRg were
      inversely related for the entire cohort, and this relationship was not
      significantly different from hyperbolic. The inverse relationship between Si and
      AIRg was not significantly different when compared between groups based on
      fasting glucose (normal fasting glucose [NFG], FPG <5.56 mmol/l vs. IFG, FPG 5.56
      6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was
      left shifted in the IFG compared with NFG group (P < 0.001) and was progressively
      more left shifted with decreasing Kg (P < 0.001), consistent with decreasing beta
      cell function. These changes were not observed for the curves relating Si and
      fasting insulin, suggesting that in the fasting state beta-cell function is
      maintained even in patients with mild IFG. Finally, the disposition index (DI)
      (Si x AIRg) was calculated as a measure of beta-cell function. The DI
      progressively decreased with increasing FPG, even in the group of subjects
      classified as NFG. CONCLUSIONS: The inverse relationship between insulin
      sensitivity and AIRg is consistent with a hyperbola not only in subjects with
      normal glucose tolerance but also with mild IFG or decreased Kg. Based on a
      hyperbolic relationship, a decrease in beta-cell function can be detected as FPG
      increases, even in patients who are normal glucose tolerant.

PMID- 16443888
TI  - Prevalence of diabetes and impaired glucose tolerance in 64-year-old Swedish
      women: experiences of using repeated oral glucose tolerance tests.
AB  - OBJECTIVE: The purpose of this study was to describe the prevalence of diabetes
      and impaired glucose tolerance (IGT) in middle-aged women and to examine the
      variability and practical use of the oral glucose tolerance test (OGTT) in the
      screening for IGT and diabetes. RESEARCH DESIGN AND METHODS: All 64-year-old
      women living in Goteborg, Sweden, were invited to take part in a screening
      examination (n = 4,856). Of these, 82% (n = 3,998) responded and 53% (n = 2,595)
      participated and underwent anthropometric measurements and a 75-g standardized
      OGTT that was repeated within 2 weeks in those not showing normal glucose
      tolerance (NGT). RESULTS: The prevalences of known and new diabetes, IGT at both
      OGTTs, and impaired fasting glucose were 4.7, 4.8, 14.4, and 6.4%, respectively.
      Half of the women with diabetes were previously undiagnosed, and 37% of the
      diagnoses were based on OGTT and diabetes 2-h values at both or one of the two
      examinations. Women with IGT at both OGTTs, in comparison with those with one
      impaired and one normal OGTT, had higher BMI, waist girth, and blood pressure.
      More than 40% of the women showed impaired glucose metabolism. CONCLUSIONS: Among
      these women, the prevalence of undetected diabetes was high and repeated OGTTs
      were needed to identify and not misclassify a considerable proportion of
      patients. The degree of glucose tolerance impairment and the number of abnormal
      OGTTs were directly associated with occurrence of components of the metabolic
      syndrome.

PMID- 16443889
TI  - Association of systemic concentrations of macrophage migration inhibitory factor
      with impaired glucose tolerance and type 2 diabetes: results from the Cooperative
      Health Research in the Region of Augsburg, Survey 4 (KORA S4).
AB  - OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a central cytokine in
      innate immunity. MIF expression can be regulated by glucose and insulin, but data
      on the association with type 2 diabetes are sparse. The aim of this study was to
      test whether MIF is associated with impaired glucose tolerance (IGT) and type 2
      diabetes and whether these associations are independent of metabolic and
      immunological risk factors and to compare the associations of MIF and IGT/type 2
      diabetes with those of C-reactive protein (CRP) and interleukin-6 (IL-6) with
      IGT/type 2 diabetes. RESEARCH DESIGN AND METHODS: The Cooperative Health Research
      in the Region of Augsburg/Kooperative Gesundheitsforschung im Raum Augsburg,
      Survey 4 (KORA S4) is a population-based survey performed in Southern Germany
      (1999-2001). Of 1,653 participants aged 55-74 years, 236 patients with type 2
      diabetes, 242 subjects with IGT, and 244 normoglycemic control subjects matched
      for age and sex were included in this cross-sectional study. Serum concentrations
      of MIF were measured by enzyme-linked immunosorbent assay. RESULTS: Serum MIF
      concentrations are highly increased in individuals with IGT and type 2 diabetes.
      The associations of MIF with IGT and type 2 diabetes were independent of
      classical risk factors and of CRP and IL-6 and were much stronger before and
      after multivariate adjustment than the associations of CRP and IL-6 with IGT and
      type 2 diabetes. CONCLUSIONS: Our data suggest that elevations of systemic MIF
      concentrations precede the onset of type 2 diabetes. This finding may be relevant
      because MIF has been reported to contribute to the development of type 2 diabetes
      related diseases such as atherosclerosis and cancer.

PMID- 16443890
TI  - Clustering of cardiovascular risk factors associated with the insulin resistance
      syndrome: assessment by principal component analysis in young hyperandrogenic
      women.
AB  - OBJECTIVE: Hyperinsulinemia is often associated with several metabolic
      abnormalities and increased blood pressure, which are risk factors for
      cardiovascular disease. It has been hypothesized that insulin resistance may
      underlie all these features. However, recent data suggest that some links between
      insulin resistance and these alterations may be indirect. The aim of our study
      was to further investigate this issue in a sample of young hyperandrogenic women,
      who often show insulin resistance and other metabolic abnormalities typical of
      the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: We tested the
      hypothesis of a single factor underlying these features by principal component
      analysis, which should recognize one component if a single mechanism explains
      this association. The analysis was carried out in a sample of 255 young
      nondiabetic hyperandrogenic women. Variables selected for this analysis included
      the basic features of the insulin resistance syndrome and some endocrine
      parameters related to hyperandrogenism. RESULTS: Principal component analysis
      identified four separate factors, explaining 64.5% of the total variance in the
      data: the first included fasting and postchallenge insulin levels, BMI,
      triglycerides, HDL cholesterol, and uric acid; the second, BMI, blood pressure,
      and serum free testosterone; the third, fasting plasma glucose, postchallenge
      glucose and insulin levels, serum triglycerides, and free testosterone; and the
      fourth, postchallenge plasma insulin, serum free testosterone, and gonadotropin
      releasing hormone agonist-stimulated 17-hydroxyprogesterone. CONCLUSIONS: These
      results support the hypothesis of multiple determinants in the clustering of
      abnormalities in the so-called insulin resistance syndrome.

PMID- 16443891
TI  - Mesenteric fat thickness is an independent determinant of metabolic syndrome and
      identifies subjects with increased carotid intima-media thickness.
AB  - OBJECTIVE: Mesenteric fat, a reflection of visceral adiposity, may play an
      important role in the pathogenesis of metabolic syndrome and cardiovascular
      diseases (CVD). In this study, we examined the independent relationship between
      mesenteric fat thickness and metabolic syndrome and defined its optimal cutoff
      value to identify high-risk subjects for metabolic syndrome and CVD. RESEARCH
      DESIGN AND METHODS: A total of 290 Chinese subjects had an ultrasound examination
      for measurements of thickness of mesenteric, preperitoneal, and subcutaneous fat
      as well as carotid intima-media thickness (IMT). Anthropometric measurements and
      metabolic risk profile were assessed by physical examination and blood taking.
      RESULTS: Twenty (6.9%) subjects had metabolic syndrome according to the National
      Cholesterol Education Panel Adult Treatment Panel III criteria with Asian
      definitions for central obesity (waist circumference >80 cm in women and >90 cm
      in men). Mesenteric fat thickness had significant correlations (P < 0.05) with
      various metabolic variables. On multivariate regression, mesenteric fat thickness
      was an independent determinant of all components of metabolic syndrome after
      adjustment for age, sex, homeostasis model assessment of insulin resistance, and
      other fat deposits. The odds ratio of metabolic syndrome was increased by 1.35
      (95% CI 1.10-1.66)-fold for every 1-mm increase in mesenteric fat thickness. On
      receiver-operating characteristic curve analysis, mesenteric fat thickness of >
      or =10 mm was the optimal cutoff value to identify metabolic syndrome, with
      sensitivity of 70% and specificity of 75%. Subjects with mesenteric fat thickness
      > or =10 mm had higher carotid IMT than those with thickness <10 mm (0.73 +/-
      0.19 vs. 0.64 +/- 0.16 mm, P = 0.001). CONCLUSIONS: Mesenteric fat thickness was
      an independent determinant of metabolic syndrome and identified subjects with
      increased carotid IMT.

PMID- 16443892
TI  - Lifestyle intervention is associated with lower prevalence of urinary
      incontinence: the Diabetes Prevention Program.
AB  - OBJECTIVE: Diabetes is associated with increased urinary incontinence risk.
      Weight loss improves incontinence, but exercise may worsen this condition. We
      examined whether an intensive lifestyle intervention or metformin therapy among
      overweight pre-diabetic women was associated with a lower prevalence of
      incontinence. RESEARCH DESIGN AND METHODS: We analyzed data from the Diabetes
      Prevention Program, a randomized controlled trial in 27 U.S. centers. Of the
      1,957 women included in this analysis, 660 (34%) were randomized to intensive
      lifestyle therapy, 636 (32%) to metformin, and 661 (34%) to placebo with standard
      lifestyle advice. The main outcome measure was incontinence symptoms by frequency
      and type by a validated questionnaire completed at the end-of-trial visit (mean
      2.9 years). RESULTS: The prevalence of total (stress or urge) weekly incontinence
      was lower among women in the intensive lifestyle group (38.3%) than those
      randomized to metformin (48.1%) or placebo (45.7%). This difference was most
      apparent among women with stress incontinence (31.3% for intensive lifestyle
      group vs. 39.7% for metformin vs. 36.7% for placebo, P = 0.006). Changes in
      weight accounted for most of the protective effect of the intensive lifestyle
      intervention on stress incontinence. CONCLUSIONS: Less-frequent urinary
      incontinence may be a powerful motivator for women to choose lifestyle
      modification to prevent diabetes.

PMID- 16443893
TI  - Coronary heart disease risk equivalence in diabetes depends on concomitant risk
      factors.
AB  - OBJECTIVE: Diabetes has been defined as a coronary heart disease (CHD) risk
      equivalent, and more aggressive treatment goals have been proposed for diabetic
      patients. RESEARCH DESIGN AND METHODS: We studied the influence of single and
      multiple risk factors on the 10-year cumulative incidence of fatal and nonfatal
      CHD and cardiovascular disease (CVD) in diabetic and nondiabetic men and women,
      with and without baseline CHD or CVD, in a population (n = 4,549) with a high
      prevalence of diabetes. RESULTS: In both sexes, diabetes increased the risk for
      CHD (hazard ratio 1.99 and 2.93 for men and women, respectively). Diabetic men
      and women had a 10-year cumulative incidence of CHD of 25.9 and 19.1%,
      respectively, compared with 57.4 and 58.4% for nondiabetic men and women with
      previous CHD. The pattern was similar when only fatal events were considered.
      Diabetic individuals with one or two risk factors had a 10-year cumulative
      incidence of CHD that was only 1.4 times higher than that of nondiabetic
      individuals (14%). However, the 10-year incidence of CHD in diabetic subjects
      with multiple risk factors was >40%, and the incidence of fatal CHD was higher in
      these subjects than in nondiabetic subjects with previous CHD. Data for CVD
      showed similar patterns, as did separate analyses by sex. CONCLUSIONS: Our
      results and comparisons with other available data show wide variation in the rate
      of CHD in diabetes, depending on the population and existing risk factors. Most
      individuals had a 10-year cumulative incidence >20%, but only those with multiple
      risk factors had a 10-year cumulative incidence that was equivalent to that of
      patients with CHD. Until more data are available, it may be prudent to consider
      targets based on the entire risk factor profile rather than just the presence of
      diabetes.

PMID- 16443894
TI  - Coffee, caffeine, and risk of type 2 diabetes: a prospective cohort study in
      younger and middle-aged U.S. women.
AB  - OBJECTIVE: High habitual coffee consumption has been associated with a lower risk
      of type 2 diabetes, but data on lower levels of consumption and on different
      types of coffee are sparse. RESEARCH DESIGN AND METHODS: This is a prospective
      cohort study including 88,259 U.S. women of the Nurses' Health Study II aged 26
      46 years without history of diabetes at baseline. Consumption of coffee and other
      caffeine-containing foods and drinks was assessed in 1991, 1995, and 1999. We
      documented 1,263 incident cases of confirmed type 2 diabetes between 1991 and
      2001. RESULTS: After adjustment for potential confounders, the relative risk of
      type 2 diabetes was 0.87 (95% CI 0.73-1.03) for one cup per day, 0.58 (0.49-0.68)
      for two to three cups per day, and 0.53 (0.41-0.68) for four or more cups per day
      compared with nondrinkers (P for trend <0.0001). Associations were similar for
      caffeinated (0.87 [0.83-0.91] for a one-cup increment per day) and decaffeinated
      (0.81 [0.73-0.90]) coffee and for filtered (0.86 [0.82-0.90]) and instant (0.83
      [0.74-0.93]) coffee. Tea consumption was not substantially associated with risk
      of type 2 diabetes (0.88 [0.64-1.23] for four or more versus no cups per day; P
      for trend = 0.81). CONCLUSIONS: These results suggest that moderate consumption
      of both caffeinated and decaffeinated coffee may lower risk of type 2 diabetes in
      younger and middle-aged women. Coffee constituents other than caffeine may affect
      the development of type 2 diabetes.

PMID- 16443895
TI  - The importance of waist circumference in the definition of metabolic syndrome:
      prospective analyses of mortality in men.
AB  - OBJECTIVE: The purpose of this study was to compare the predictive ability of the
      National Cholesterol Education Panel (NCEP), revised NCEP (NCEP-R), and
      International Diabetes Federation (IDF) metabolic syndrome criteria for mortality
      risk, and to examine the effects of waist circumference on mortality within the
      context of these criteria. RESEARCH DESIGN AND METHODS: The sample included
      20,789 white, non-Hispanic men 20-83 years of age from the Aerobics Center
      Longitudinal Study. The main outcome measures were all-cause and cardiovascular
      disease (CVD) mortality over 11.4 years of follow-up. RESULTS: The proportions of
      men with the metabolic syndrome were 19.7, 27, and 30% at baseline, respectively,
      according to NCEP, NCEP-R, and IDF criteria. A total of 632 deaths (213 CVD)
      occurred. The relative risks (RRs) and 95% CIs of all-cause mortality were 1.36
      (1.14-1.62), 1.31 (1.11-1.54), and 1.26 (1.07-1.49) for the NCEP, NCEP-R, and IDF
      definitions, respectively. The corresponding RRs for CVD mortality were 1.79
      (1.35-2.37), 1.67 (1.27-2.19), and 1.67 (1.27-2.20). Additionally, there was a
      significant trend for a higher risk of CVD mortality across waist circumference
      categories (<94, 94-102, and >102 cm) among men with at least two additional
      metabolic syndrome risk factors (P = 0.01). CONCLUSIONS: The prediction of
      mortality with IDF and NCEP metabolic syndrome criteria was comparable in men.
      Waist circumference is a valuable component of metabolic syndrome; however, the
      IDF requirement of an elevated waist circumference warrants caution given that a
      large proportion of men with normal waist circumference have multiple risk
      factors and an increased risk of mortality.

PMID- 16443896
TI  - Risk scores for type 2 diabetes can be applied in some populations but not all.
AB  - OBJECTIVE: Risk scores based on phenotypic characteristics to identify
      individuals at high risk of having undiagnosed diabetes have been developed in
      Caucasian populations. The impact of known risk factors on having undiagnosed
      type 2 diabetes differs between populations from different ethnic origin, and
      risk scores developed in Caucasians may not be applicable to other ethnic groups.
      This study evaluated the performance of one risk score in nine populations of
      diverse ethnic origin. RESEARCH DESIGN AND METHODS: Data provided by centers from
      around the world to the DETECT-2 project were used. The database includes
      population-based surveys with information on at least 500 people without known
      diabetes having a 75-g oral glucose tolerance test. To date, 52 centers have
      contributed data on 190,000 individuals from 34 countries. In this analysis, nine
      cross-sectional studies were selected representing diverse ethnic and regional
      backgrounds. The risk score assessed uses information on age, sex, blood pressure
      treatment, and BMI. RESULTS: This analysis included 29,758 individuals; 1,805
      individuals had undiagnosed diabetes. The performance of the risk score varied
      widely, with sensitivity, specificity, and percentage needing further testing
      ranging between 12 and 57%, 72 and 93%, and 2 and 25%, respectively, with the
      worse performance in non-Caucasian populations. This variation in performance was
      related to differences in the association between prevalence of undiagnosed
      diabetes and components of the risk score. CONCLUSIONS: A typical risk score
      developed in Caucasian populations cannot be applied to other populations of
      diverse ethnic origins.

PMID- 16443897
TI  - Identification of linguistic barriers to diabetes knowledge and glycemic control
      in Chinese Americans with diabetes.

PMID- 16443898
TI  - Diet therapy with diacylglycerol oil delays the progression of renal failure in
      type 2 diabetic patients with nephropathy.

PMID- 16443899
TI  - An epidemiologic profile of children with diabetes in the U.S.

PMID- 16443900
TI  - Hemocue urine albumin point-of-care test shows strong agreement with the results
      obtained with a large nephelometer.

PMID- 16443901
TI  - Association between elevated serum C-reactive protein and triglyceride levels in
      young subjects with type 1 diabetes.

PMID- 16443902
TI  - Glycemia and corrected QT interval prolongation in young type 1 diabetic
      patients: what is the relation?

PMID- 16443903
TI  - Recurrent comas due to secret self-administration of insulin in adolescents with
      type 1 diabetes.

PMID- 16443904
TI  - Insulin resistance and the cluster of abnormalities related to the metabolic
      syndrome are associated with reduced glomerular filtration rate in patients with
      type 2 diabetes.

PMID- 16443905
TI  - Emerging therapies mimicking the effects of amylin and glucagon-like peptide 1.

PMID- 16443906
TI  - Gut and adipocyte peptides.

PMID- 16443907
TI  - Diabetes and coronary risk equivalency: what does it mean?

PMID- 16443908
TI  - Flare-up of serum amylase prior to onset of lethal ketoacidosis in a patient with
      fulminant type 1 diabetes.

PMID- 16443909
TI  - Prevalence of the metabolic syndrome in the elderly population according to IDF,
      WHO, and NCEP definitions and associations with C-reactive protein: the KORA
      Survey 2000.

PMID- 16443910
TI  - Betel nut chewing is independently associated with urinary albumin excretion rate
      in type 2 diabetic patients.

PMID- 16443911
TI  - Effect of multifactorial intervention on diabetic macular edema.

PMID- 16443912
TI  - Evaluation of a diagnostic algorithm for hereditary hemochromatosis in 3,500
      patients with diabetes.

PMID- 16443913
TI  - The -8503 G/A polymorphism of the adiponectin receptor 1 gene is associated with
      insulin sensitivity dependent on adiposity.

PMID- 16443914
TI  - On the weighted-average relationship between plasma glucose and HbA1c.

PMID- 16443915
TI  - Hypoglycemia preceding fatal car collisions.

PMID- 16443916
TI  - Association of serum fetuin-A with insulin resistance in type 2 diabetic and
      nondiabetic subjects.

PMID- 16443917
TI  - Insulin signaling, glucose metabolism, and the angiotensin II signaling system:
      studies in Bartter's/Gitelman's syndromes.

PMID- 16443918
TI  - Endogenous secretory receptor for advanced glycation end product levels are
      inversely associated with HbA1c in type 2 diabetic patients.

PMID- 16443919
TI  - The use of insulin glargine with gestational diabetes mellitus.

PMID- 16443920
TI  - Exenatide (exendin-4)-induced pancreatitis: a case report.

PMID- 16443921
TI  - Bowel dysfunction in Wolfram syndrome.

PMID- 16443923
TI  - Metformin in pregnancy: its time has not yet come.

PMID- 16443922
TI  - Objective evidence for the reversibility of nerve injury in diabetic neuropathic
      cachexia.

PMID- 16443924
TI  - Aspects of the design and analysis of high-dimensional SNP studies for disease
      risk estimation.
AB  - The state of readiness for high-dimensional single nucleotide polymorphism (SNP)
      epidemiologic association studies is described, as background for a discussion of
      statistical aspects of case-control study design and analysis. Specifically, the
      important role that multistage designs can play in the elimination of false
      positive associations and in the control of study costs will be noted. Also, the
      trade-offs associated with using pooled DNA at early design stages for additional
      important cost reductions will be discussed in some detail. An odds ratio
      approach to relating SNP alleles to disease risk using pooled DNA will be
      proposed, in conjunction with a simple empirical variance estimator, based on
      comparisons among log-odds ratio estimators from distinct pairs of case and
      control pools. Simulation studies will be presented to evaluate the moderate
      sample size properties of such multistage designs and estimation procedures. The
      design of an ongoing three-stage study in the Women's Health Initiative to relate
      250,000 SNPs to the risk of coronary heart disease, stroke, and breast cancer
      will provide illustration, and will be used to motivate the choice of simulation
      configurations.

PMID- 16443925
TI  - Altered mammary gland development in male rats exposed to genistein and
      methoxychlor.
AB  - Genistein (GE) is a prevalent phytoestrogen whose presence in human and animal
      foods may affect biological actions of synthetic endocrine active compounds. We
      have previously reported that in utero and lactational exposure to high doses of
      GE or the endocrine active pesticide methoxychlor (MXC) caused mammary epithelial
      proliferation in 21-day-old male rats. Combined exposure to GE and MXC resulted
      in significant feminization of the male mammary glands. The goals of the current
      study were to evaluate mammary responses to GE and MXC at the adult stage and
      investigate relevant mechanisms. Following in utero, lactational exposure
      (through maternal diet), and direct dietary exposure, the inguinal mammary gland
      of male rats (90 days of age) was found to exhibit significant morphological
      alterations in the groups treated with GE and/or MXC compared to the control. GE
      exposure (at 300 and 800 ppm concentrations) caused lobular enlargement and
      epithelial proliferation, whereas MXC exposure (800 ppm) led to ductal elongation
      and lobular enlargement. Combining the two treatments caused prominent
      proliferation of both ducts and alveoli; secretory material was seen in readily
      recognizable alveolar lumens, which are absent in untreated male mammary. We also
      surveyed gene expression in the mammary tissue using a cDNA microarray and
      evaluated relevant protein factors. The results indicated that the treatment
      effects are likely due to interactions between steroid hormone receptor-mediated
      signals and growth factor-driven cellular pathways. The distinctive responses
      associated with the GE+MXC combination were likely linked to enhanced actions of
      insulin-like growth factor 1 and related downstream pathways.

PMID- 16443926
TI  - The apoptotic effect of brucine from the seed of Strychnos nux-vomica on human
      hepatoma cells is mediated via Bcl-2 and Ca2+ involved mitochondrial pathway.
AB  - In an attempt to dissect the mechanism of Strychnos nux-vomica, a commonly used
      Chinese folk medicine in the therapy of liver cancer, the cytotoxic effects of
      four alkaloids in Strychnos nux-vomica, brucine, brucine N-oxide, strychnine, and
      isostrychnine, on human hepatoma cells (HepG2) were screened by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrasolium bromide (MTT) assay. Brucine,
      among the four alkaloids, exhibited the strongest toxic effect, the mechanism of
      which was found to cause HepG2 cell apoptosis, since brucine caused HepG2 cell
      shrinkage, the formation of apoptotic bodies, DNA fragmentation, cell cycle
      arrest, as well as phosphatidylserine externalization, all of which are typical
      characteristics of apoptotic programmed cell death. Brucine-induced HepG2 cell
      apoptosis was caspase dependent, with caspase-3 activated by caspase-9. Brucine
      also caused the proteolytic processing of caspase-9. In addition, brucine caused
      depolarization of the mitochondrial membrane of HepG2 cells, the inhibition of
      which by cyclosporine A completely abrogated the activation of casapses and
      release of cytochrome c in brucine-treated HepG2 cells. These findings suggested
      a pivotal role of mitochondrial membrane depolarization in HepG2 cell apoptosis
      elicited by brucine. Furthermore, brucine induced a rapid and sustained elevation
      of intracellular [Ca2+], which compromised the mitochondrial membrane potential
      and triggered the process of HepG2 cell apoptosis. Finally, Bcl-2 was found to
      predominately control the whole event of cell apoptosis induced by brucine. The
      elevation of [Ca2+]i caused by brucine was also suppressed by overexpression of
      Bcl-2 protein in HepG2 cells. From the facts given above, Ca2+ and Bcl-2 mediated
      mitochondrial pathway were found to be involved in brucine-induced HepG2 cell
      apoptosis.

PMID- 16443928
TI  - Extracellular matrix metalloproteinase inducer (CD147) confers resistance of
      breast cancer cells to Anoikis through inhibition of Bim.
AB  - Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or
      CD147), a member of the immunoglobulin family and a glycoprotein enriched on the
      surface of tumor cells, promotes invasion, metastasis, and growth and survival of
      malignant cells and confers resistance to some chemotherapeutic drugs. However,
      the molecular mechanisms underlying the actions of EMMPRIN are not fully
      understood. In this study we sought to determine whether EMMPRIN contributes to
      the malignant phenotype of breast cancer by inhibiting anoikis, a form of
      apoptosis induced by loss or alteration of cell-cell or cell-matrix anchorage,
      and to explore the signaling pathways involved. We found that in the absence of
      attachment, human breast carcinoma cells expressing high levels of EMMPRIN formed
      less compact aggregates with larger surface area and less fibronectin matrix
      assembly, had higher viability, and were resistant to anoikis. Knockdown of
      EMMPRIN expression by RNA interference (small interfering RNA or short hairpin
      RNA) sensitized cancer cells to anoikis, as demonstrated by activation of caspase
      3, increased DNA fragmentation, and decreased cellular viability. Furthermore, we
      observed that the accumulation of Bim, a proapoptotic BH3-only protein, was
      reduced in EMMPRIN-expressing cells and that silencing of EMMPRIN expression
      elevated Bim protein levels and enhanced cellular sensitivity to anoikis.
      Treatment of cells with a MEK inhibitor (U0126) or proteasome inhibitor
      (epoxomicin) also up-regulated Bim accumulation and rendered cells more sensitive
      to anoikis. These results indicated that expression of EMMPRIN protects cancer
      cells from anoikis and that this effect is mediated at least in part by a MAP
      kinase-dependent reduction of Bim. Because anoikis deficiency is a key feature of
      neoplastic transformation and invasive growth of epithelial cancer cells, our
      study on the role of EMMPRIN in anoikis resistance and the mechanism involved
      underscores the potential of EMMPRIN expression as a prognostic marker and novel
      target for cancer therapy.

PMID- 16443929
TI  - Solution structure of a post-transition state analog of the phosphotransfer
      reaction between the A and B cytoplasmic domains of the mannitol transporter
      IIMannitol of the Escherichia coli phosphotransferase system.
AB  - The solution structure of the post-transition state complex between the isolated
      cytoplasmic A (IIAMtl) and phosphorylated B (phospho-IIBMtl) domains of the
      mannitol transporter of the Escherichia coli phosphotransferase system has been
      solved by NMR. The active site His-554 of IIAMtl was mutated to glutamine to
      block phosphoryl transfer activity, and the active site Cys-384 of IIBMtl
      (residues of IIBMtl are denoted in italic type) was substituted by serine to
      permit the formation of a stable phosphorylated form of IIBMtl. The two
      complementary interaction surfaces are predominantly hydrophobic, and two
      methionines on IIBMtl, Met-388 and Met-393, serve as anchors by interacting with
      two deep pockets on the surface of IIAMtl. With the exception of a salt bridge
      between the conserved Arg-538 of IIAMtl and the phosphoryl group of phospho
      IIBMtl, electrostatic interactions between the two proteins are limited to the
      outer edges of the interface, are few in number, and appear to be weak. This
      accounts for the low affinity of the complex (Kd approximately 3.7 mm), which is
      optimally tuned to the intact biological system in which the A and B domains are
      expressed as a single polypeptide connected by a flexible 21-residue linker. The
      phosphoryl transition state can readily be modeled with no change in protein
      protein orientation and minimal perturbations in both the backbone immediately
      adjacent to His-554 and Cys-384 and the side chains in close proximity to the
      phosphoryl group. Comparison with the previously solved structure of the IIAMtl
      HPr complex reveals how IIAMtl uses the same interaction surface to recognize two
      structurally unrelated proteins and explains the much higher affinity of IIAMtl
      for HPr than IIBMtl.

PMID- 16443930
TI  - siRecords: an extensive database of mammalian siRNAs with efficacy ratings.
AB  - Short interfering RNAs (siRNAs) have been gaining popularity as the gene knock
      down tool of choice by many researchers because of the clean nature of their
      workings as well as the technical simplicity and cost efficiency in their
      applications. We have constructed siRecords, a database of siRNAs experimentally
      tested by researchers with consistent efficacy ratings. This database will help
      siRNA researchers develop more reliable siRNA design rules; in the mean time,
      siRecords will benefit experimental researchers directly by providing them with
      information about the siRNAs that have been experimentally tested against the
      genes of their interest. Currently, more than 4100 carefully annotated siRNA
      sequences obtained from more than 1200 published siRNA studies are hosted in
      siRecords. This database will continue to expand as more experimentally tested
      siRNAs are published. AVAILABILITY: The siRecords database can be accessed at
      http://siRecords.umn.edu/siRecords/

PMID- 16443931
TI  - LC-MS-based method for the qualitative and quantitative analysis of complex lipid
      mixtures.
AB  - A simple and robust LC-MS-based methodology for the investigation of lipid
      mixtures is described, and its application to the analysis of human lipoprotein
      associated lipids is demonstrated. After an optional initial fractionation on
      Silica 60, normal-phase HPLC-MS on a YMC PVA-Sil column is used first for class
      separation, followed by reversed-phase LC-MS or LC-tandem mass spectrometry using
      an Atlantis dC18 capillary column, and/or nanospray MS, to fully characterize the
      individual lipids. The methodology is applied here for the analysis of human
      apolipoprotein B-associated lipids. This approach allows for the determination of
      even low percentages of lipids of each molecular species and showed clear
      differences between lipids associated with apolipoprotein B-100-LDL isolated from
      a normal individual and those associated with a truncated version, apolipoprotein
      B-67-containing lipoproteins, isolated from a homozygote patient with familial
      hypobetalipoproteinemia. The methods described should be easily adaptable to most
      modern MS instrumentation.

PMID- 16443933
TI  - Opportunities needed for educators.

PMID- 16443932
TI  - Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter.
AB  - It has been suggested that the signal transduction initiated by apolipoprotein A
      I (apoA-I) activates key proteins involved in cholesterol efflux. ABCA1 serves as
      a binding partner for apoA-I, but its participation in apoA-I-induced signaling
      remains uncertain. We show that the exposure of human fibroblasts to ABCA1
      ligands (apolipoproteins and amphipathic helical peptides) results in the
      generation of intracellular signals, including activation of the small G-protein
      Cdc42, protein kinases (PAK-1 and p54JNK), and actin polymerization. ApoA-I
      induced signaling was abrogated by glyburide, an inhibitor of the ABC transporter
      family, and in fibroblasts from patients with Tangier disease, which do not
      express ABCA1. Conversely, induction of ABCA1 expression with the liver X
      receptor agonist, T0901317, and the retinoid X receptor agonist, R0264456,
      potentiated apoA-I-induced signaling. Similar effects were observed in HEK293
      cells overexpressing ABCA1-green fluorescent protein (GFP) fusion protein, but
      not ABCA1-GFP (K939M), which fails to hydrolyze ATP, or a nonfunctional ABCA1-GFP
      with a truncated C terminus. We further found that Cdc42 coimmunoprecipitates
      with ABCA1 in ABCA1-GFP-expressing HEK293 cells exposed to apoA-I but not in
      cells expressing ABCA1 mutants. We conclude that ABCA1 transduces signals from
      apoA-I by complexing and activating Cdc42 and downstream kinases and, therefore,
      acts as a full apoA-I receptor.

PMID- 16443934
TI  - Shady shadows.

PMID- 16443935
TI  - Ordering trends in the ER.

PMID- 16443936
TI  - Legal and practice standards implications.

PMID- 16443937
TI  - Osteoarthritis and the Rosenberg method.

PMID- 16443938
TI  - Online education: a survey of faculty and students.
AB  - OBJECTIVE: This study examines faculty and student perspectives related to online
      learning. METHOD: Baccalaureate-degree radiologic technology students and
      graduate nursing students were surveyed to determine their support for online
      education. Additionally, faculty at the same institution who were experienced in
      online teaching were surveyed. RESULTS: The results in this study agreed with
      some aspects from the body of knowledge on online learning.

PMID- 16443939
TI  - Acquiring new technology and surviving environmental pressures.
AB  - CONTEXT: The U.S. health care system faces increased pressures to expand coverage
      to the elderly, the uninsured and the poor, while maintaining costs and quality
      of care. Because of the federal budget deficit and continued fiscal
      uncertainties, resource allocation will become even more scrutinized. OBJECTIVE:
      How does a health care system allocate limited funds and still provide quality
      care using innovative technology? METHOD: This article reviews the literature on
      the acquisition of new technologies from a theoretical perspective, using
      positron emission tomography (PET) as an example. A unified model, including
      concepts from the resource dependency theory (RDT) supplemented with
      organizational survival concepts from the ecological theory, was used to analyze
      resource acquisition for technological innovation and organizational survival. An
      attempt was made to evaluate a hospital's profit maximization, recognition as a
      center of clinical excellence and role as a technological leader of the community
      with respect to acquisition of PET equipment. CONCLUSION: Organizations acquire
      new technology for a variety of reasons that can be explained by RDT and
      ecological theory concepts. In terms of the profit maximization motive, hospitals
      purchase PET equipment to enhance revenue generation. From the clinical
      excellence perspective, organizations seek the best available technology to meet
      the needs of their patients. Finally, hospitals adopt new technology to enhance
      their image as a technological leader.

PMID- 16443940
TI  - Blunt pelvic trauma.

PMID- 16443941
TI  - Osteoporosis in men.

PMID- 16443942
TI  - Contrast agents.

PMID- 16443943
TI  - Descriptive epidemiology of vestibular schwannomas.
AB  - Vestibular schwannomas, commonly termed acoustic neuromas, arise from the
      vestibular branch of the eighth cranial nerve (acoustic nerve) and are benign,
      slow-growing brain tumors that negatively impact patient quality of life. They
      are thought to account for the majority of intracranial nerve sheath tumors. To
      describe incidence rate patterns and trends of primary nerve sheath tumors of the
      brain/CNS and the subset of vestibular schwannomas in two population-based
      incidence registries, data were obtained from 11 Central Brain Tumor Registry of
      the United States (CBTRUS) collaborating state registries and the Los Angeles
      County Cancer Surveillance Program (LACCSP) (1975-1998). Average annual incidence
      rates were tabulated by age, gender, race, year, and region and were age-adjusted
      to the year 2000 U.S. standard population. Multiplicative Poisson regression
      models were used to compare trends in primary nerve sheath tumors of the
      brain/CNS overall and in subgroups, including vestibular schwannomas, controlling
      for age, gender, race, microscopic confirmation, and region. Joinpoint regression
      analysis was used to identify any sharp changes in incidence over time. The
      overall incidence of primary nerve sheath tumors of the brain/CNS was 1.1 per
      100,000 person-years (CBTRUS, 1995-1999 and LACCSP, 1995-1998). The incidence of
      vestibular schwannomas was similar for both data sets: 0.6 per 100,000 person
      years (CBTRUS, 1995-1999) and 0.8 per 100,000 person-years (LACCSP, 1995-1998).
      Moreover, the incidence of primary nerve sheath tumors of the brain/CNS overall
      (CBTRUS, 1985-1999 and LACCSP, 1975-1998) and of vestibular schwannomas (CBTRUS,
      1992-1999 and LACCSP, 1992-1998) increased over time. However, the incidence of
      benign schwannomas in sites other than the acoustic nerve either decreased
      (CBTRUS, 1992-1999) or experienced no significant change (LACCSP, 1992-1998).
      While improvements in diagnosis and reporting may explain some of these trends,
      further consideration of potential etiologic factors may be warranted.

PMID- 16443944
TI  - Diagnostic, treatment, and demographic factors influencing survival in a
      population-based study of adult glioma patients in the San Francisco Bay Area.
AB  - We compare survival estimates for population-based glioma cases by using two
      diagnostic coding schemes, (1) the International Classification of Diseases,
      Oncology, second edition (ICD-O-2) as reported by the Surveillance, Epidemiology,
      and End Results (SEER) program and (2) central neuropathology review diagnosis
      based on the World Health Organization II classification. In addition, among
      review categories, we estimate survival in relation to several patient
      demographic and treatment factors. Eligible cases included adults residing in the
      San Francisco Bay SEER Area with newly diagnosed, histologically confirmed glioma
      during the years 1991-1994 and 1997-1999. The study group included participating
      subjects for whom subsequent central neuropathology review confirmed glioma. We
      determined treatments, vital status, and other factors by using registry,
      interview, medical record, and active follow-up data. Survival differences
      between anaplastic astrocytoma (AA) and astrocytoma were apparent from review
      diagnoses (median months of survival for AA, 13.0 [95% CI, 9.9-19.5], and
      astrocytoma, 101.3 [95% CI lower limit, 42.1; upper limit not yet reached]), but
      not with ICD-O-2 diagnoses reported by SEER (median months of survival for AA,
      16.6 [95% CI, 12.0-20.7], and astrocytoma, not otherwise specified, 17.2 [95% CI,
      10.6-71.6]). This finding emphasizes the need for improvements in coding for
      nonglioblastoma astrocytomas to provide better population survival estimates.
      When review diagnosis was used, younger age and resection (vs. biopsy) were
      statistically significant for all histology groups analyzed by multivariable Cox
      proportional hazard models. Additional statistically significant variables were
      as follows: among 517 glioblastoma patients, radiation treatment and being
      married; among 105 AA patients, inclusion of chemotherapy in the initial
      treatment; and among 106 patients with nonanaplastic oligodendroglial tumors,
      college education. Further consideration of impact of marital status, education,
      and other social factors in glioma survival may be warranted.

PMID- 16443945
TI  - Temporal trends in incidence of primary brain tumors in the United States, 1985
      1999.
AB  - A number of reports have indicated an increasing incidence of primary brain
      tumors over the past few decades. The purpose of this study was to describe
      incidence rate trends in a population-based series of newly diagnosed primary
      nonmalignant and malignant brain and other CNS tumors, contributing five
      additional years to previously published incidence trends. Data for the years
      1985 through 1999 from six collaborating state cancer registries of the Central
      Brain Tumor Registry of the United States were used to determine incidence trends
      in the broad age groups 0-19, 20-64, and >or=65 years, overall and for selected
      histologies. Multiplicative Poisson regression was used to express trends as
      average annual percent change (AAPC). Joinpoint regression was used to identify
      sharp changes in incidence occurring over this period. Overall, incidence
      increased modestly (AAPC, 1.1; 95% CI, 0.8-1.4). When brain lymphomas were
      excluded, this increase remained statistically significant. A sharp change in
      incidence of brain lymphomas from increasing to decreasing over time was
      identified. Specific histologies that were increasing included anaplastic
      astrocytomas in individuals aged >or=65 years, microscopically confirmed gliomas
      in both adult age groups, and microscopically confirmed glioma, not otherwise
      specified (NOS), in children. Increases that were not specific to any population
      subgroup were seen for oligodendrogliomas, ependymomas, meningiomas, and nerve
      sheath tumors. Decreases were noted for astrocytoma, NOS, nonmicroscopically
      confirmed gliomas, and pituitary tumors. Improvements in diagnosis and
      classification are likely reflected in the decreasing trends in unspecified
      glioma subgroups and the accompanying increasing trends in more specific glioma
      subgroups. However, increases in meningiomas and nerve sheath tumors deserve
      further attention.

PMID- 16443946
TI  - Comparison of linear and volumetric criteria in assessing tumor response in adult
      high-grade gliomas.
AB  - The Response Evaluation Criteria in Solid Tumors, or RECIST criteria (one
      dimensional [1D] measurement), are widely used to measure response in tumors, but
      there are few studies evaluating these criteria in brain tumors. We compared
      linear and volumetric measurements in adult high-grade supratentorial enhancing
      gliomas to determine the agreement between measurements, in defining responses
      and in their subsequent relation to survival. We hypothesized that the 1D RECIST
      criteria maybe suitable for response assessment in adult high-grade gliomas.
      Tumor size on MRI scans in 104 patients with high-grade enhancing gliomas treated
      on clinical trial protocols was measured by using 1D (greatest length), 2D (two
      dimensional: product of the two longest perpendicular diameters), 3D (three
      dimensional: product of the longest perpendicular diameters in one plane and the
      longest orthogonal diameter to that plane), enhancing volume (EV), and total
      volume (TV). A total of 388 T1 postgadolinium MRI scans (104 baseline and 284
      follow-up scans) were evaluated. Volumetric analysis (EV and TV) was performed
      with commercially available software. Intraobserver and interobserver
      correlations (rho) were high for all modalities (rho > 0.92 and rho > 0.71,
      respectively). Correlation was excellent (rho > 0.9) among all modalities except
      for 3D (rho < 0.6). Patient response rates ranged from 12% to 26%. Median
      progression-free survival (mPFS) and six-month progression-free survival (6mPFS)
      were not significantly different among the methods (range, 5.3 months to 5.9
      months and 42% to 48%, respectively). Landmark analyses of response at two months
      using linear methods predicted overall survival with hazard ratios of 0.19 to
      0.29 (P < 0.005). These results suggest high concordance among 1D, 2D, TV, and
      EV, but not 3D, methods in assessing enhancing tumor progression and in
      estimating mPFS and 6mPFS in adult brain tumor patients. The tumor response at
      two months assessed by linear methods correlated better with overall survival.
      Thus, linear methods are comparable to volumetric methods, but simpler to
      implement for routine clinical use and for designing clinical trials of brain
      tumors.

PMID- 16443947
TI  - Phase 2 trial of radiation plus high-dose tamoxifen for glioblastoma multiforme:
      RTOG protocol BR-0021.
AB  - Preclinical studies support the concept that inhibition of protein kinase C (PKC)
      by tamoxifen (TAM) should provide both antineoplastic effects and
      radiosensitization. High-dose TAM (80 mg/m2 p.o. daily in divided doses) was
      given with and after conventional radiotherapy (XRT) to inhibit PKC-mediated
      signaling, which is known to be enhanced in glioblastoma (GBM). Seventy-seven
      patients were accrued between December 2000 and December 2001; two were
      ineligible and not included in the efficacy results. Pretreatment characteristics
      of the patients included the following: 52% were less than 60 years of age, 39%
      had a Zubrod score of 0, 70% had minor or no neurological symptoms, and 65% were
      Radiation Therapy Oncology Group-recursive partition analysis (RPA) class III and
      IV. Eighty-six percent of patients achieved acceptable dosing of TAM. Notable
      toxicity included late radiation grade 3 in two patients and thromboembolic
      events in 16 patients (two grade 2, 10 grade 3, three grade 4, and one grade 5),
      for an incidence of 20.8% (which is lower than expected, based on the literature
      for deep vein thrombophlebitis in GBM patients not receiving TAM). Median
      survival time (MST) was 9.7 months as compared (by three different statistical
      methodologies) to the historical GBM control database of 1457 RPA class III, IV,
      and V drug/XRT-treated patients. After controlling for RPA class IV, the MST was
      11.3 months, which compares to the historical RPA control of 11.3 months (P =
      0.37). The results obtained do not exhibit a substantial advance over those of
      previous studies with various XRT/drug doublets, including BCNU. However, as TAM
      does not have significant overlapping toxicities with most other drugs, its
      testing in a combined modality approach with other medications may be justified
      in future clinical trials. Historically, the incidence of thromboembolic events
      in GBM patients is approximately 30%. The lower-than-expected incidence seen here
      has also been observed in other high-dose TAM GBM studies. We speculate that TAM
      inhibited the PKC-mediated phosphorylation of coagulation factors.

PMID- 16443948
TI  - Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor
      prognosis pediatric brain tumors.
AB  - The objective of this study was to assess the efficacy of the VETOPEC regimen, a
      regimen of vincristine and etoposide with escalating doses of cyclophosphamide
      (CPA), in pediatric patients with high-risk brain tumors. Three consecutive
      studies by the Australia and New Zealand Children's Cancer Study Group--VETOPEC
      I, Baby Brain 91, and VETOPEC II--have used a specific chemotherapy regimen of
      vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with
      relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II
      cohort were treated with very high dose CPA with peripheral blood stem cell
      (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors
      treated with these intensive VETOPEC-based protocols to assess the response,
      toxicity, and survival. We also assessed whether the use of very high dose
      chemotherapy with stem cell rescue improved the response rate or affected
      toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based
      protocols. Of the 54 patients evaluable for tumor response, 17 had a complete
      response (CR) and 20 a partial response (PR) to treatment, which yielded an
      overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas,
      56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4
      astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months,
      overall survival for the entire cohort of 71 patients was 32%, with event-free
      survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II
      cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients.
      This regimen produces high response rates in a variety of very poor prognosis
      pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher
      escalation in doses of CPA did not deliver a further improvement in response.
      With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a
      limiting factor. The response rates observed support further development of this
      chemotherapy regimen.

PMID- 16443949
TI  - Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent
      glioblastoma.
AB  - Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong
      immunostimulating activity and drive the immune response toward the Th1 (T helper
      type 1) phenotype. These ODNs have shown promising efficacy in preclinical
      studies when injected locally in several cancer models. We conducted a phase 1
      trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN,
      administered intratumorally by convection-enhanced delivery in patients with
      recurrent glioblastoma. Cohorts of three to six patients were treated with
      escalating doses of CpG-28 (0.5-20 mg), and patients were observed for at least
      four months. Twenty-four patients entered the trial. All patients had previously
      been treated with radiotherapy, and most patients had received one or several
      types of chemotherapy. Median age was 58 years (range, 25-73) and median KPS was
      80% (range, 60%-100%). Adverse effects possibly or probably related to the
      studied drug were moderate and consisted mainly in worsening of neurological
      conditions (four patients), fever above 38 degrees C that disappeared within a
      few days (five patients), and reversible grade 3 lymphopenia (seven patients).
      Only one patient experienced a dose-limiting toxicity. Preliminary evidence of
      activity was suggested by a minor response observed in two patients and an
      overall median survival of 7.2 months. In conclusion, CpG-28 was well tolerated
      at doses up to 20 mg per injection in patients with recurrent glioblastoma. Main
      side effects were limited to transient worsening of neurological condition and
      fever.

PMID- 16443950
TI  - Phase 1 study of erlotinib HCl alone and combined with temozolomide in patients
      with stable or recurrent malignant glioma.
AB  - The purpose of this study was to define the maximum tolerated dose of erlotinib
      and characterize its pharmaco-kinetics and safety profile, alone and with
      temozolomide, with and without enzyme-inducing antiepileptic drugs (EIAEDs), in
      patients with malignant gliomas. Patients with stable or progressive malignant
      primary glioma received erlotinib alone or combined with temozolomide in this
      dose-escalation study. In each treatment group, patients were stratified by
      coadministration of EIAEDs. Erlotinib was started at 100 mg orally once daily as
      a 28-day treatment cycle, with dose escalation by 50 mg/day up to 500 mg/day.
      Temozolomide was administered at 150 mg/m2 for five consecutive days every 28
      days, with dose escalation up to 200 mg/m2 at the second cycle. Eightythree
      patients were evaluated. Rash, fatigue, and diarrhea were the most common adverse
      events and were generally mild to moderate. The recommended phase 2 dose of
      erlotinib is 200 mg/day for patients with glioblastoma multiforme who are not
      receiving an EIAED, 450 mg/day for those receiving temozolomide plus erlotinib
      with an EIAED, and at least 500 mg/day for those receiving erlotinib alone with
      an EIAED. Of the 57 patients evaluable for response, eight had a partial response
      (PR). Six of the 57 patients had a progression-free survival of longer than six
      months, including four patients with a PR. Coadministration of EIAEDs reduced
      exposure to erlotinib as compared with administration of erlotinib alone (33%-71%
      reduction). There was a modest pharmacokinetic interaction between erlotinib and
      temozolomide. The favorable tolerability profile and evidence of antitumor
      activity indicate that further investigation of erlotinib is warranted.

PMID- 16443951
TI  - Atypical teratoid/rhabdoid tumor evolving from an optic pathway ganglioglioma:
      case study.
AB  - We report an atypical teratoid/rhabdoid tumor arising in a ganglioglioma from an
      11-year-old male who had been treated over a nine-year period. A combined
      histologic, immunohistochemical, and molecular genetic analysis confirmed this
      diagnosis. Molecular genetic studies demonstrated a mutation in exon 9 of the
      INI1 gene in the tumor, which was not present in the patient's blood. This report
      is the first to describe progression of a ganglioglioma to atypical
      teratoid/rhabdoid tumor.

PMID- 16443952
TI  - From science to politics: the stem cell debate.

PMID- 16443953
TI  - The impact of genetic information on policy and clinical practice.
AB  - This article discusses genetics-related policy issues that have an impact on
      health care systems, health care providers, and their patients: privacy, mass
      screening, family screening, and knowledge dissemination. Access, cost, and
      ethical implications are important discussant points for each of these genetic
      related policy issues. Embedded in the issue of privacy are concerns of
      insurability, confidentiality, and discrimination. The public health policy
      implications related to mass screening programs include efficacy of the screening
      tests, availability of primary and secondary interventions, access, costs, and
      program evaluation. Policy issues for family screening are similar to mass
      screening, with added concerns about privacy and availability of adequate
      resources, including health care providers and counselors trained in genetics.
      Knowledge dissemination is critical to maintaining currency of clinical
      information and applications of genetic technologies and treatments. As genetic
      information expands, the need for knowledge dissemination will increase. The
      importance of advanced practice nurses' involvement in these policy issues is
      discussed.

PMID- 16443954
TI  - Experiences from the National Institute of Nursing Research: Summer Genetics
      Institute 2004.
AB  - The National Institute of Nursing Research (NINR) Summer Genetics Institute (SGI)
      prepares nurses with training in molecular genetics for use in clinical practice,
      research, and education. Experiences from the SGI 2004 are recounted. More than
      35 genetic experts from National Institutes of Health and surrounding
      universities in Washington, D.C., provided lecture and laboratory experiences.
      The lecture portion of the SGI focused on the molecular aspect of genetics and
      the laboratory component included experiments designed to provide an
      understanding of genetic approaches for diagnostic and research purposes. The SGI
      prepares nurses with the genetic foundation to meet the healthcare challenges of
      the future.

PMID- 16443955
TI  - Leadership and public policy.
AB  - This article outlines some of the key issues that medical science, research, and
      technology raise for society and urges nurses to play a larger role in setting
      public policy to define and regulate their future use and development. It notes
      the unique clinical and academic experiences of nurses that qualify them for this
      task and suggests specific ways these goals can be achieved through the Center
      for Health Policy, Research and Ethics at George Mason University.

PMID- 16443956
TI  - Striving for congruence: the interconnection between values, practice, and
      political action.
AB  - In the current U.S. health care system, both good health and a higher quality of
      health care are more likely to be experienced by those who have access to money,
      power, and privilege. Consequently, serious health disparities exist between the
      rich and poor, White people and people of color, and men and women. The American
      Association of Colleges of Nursing (AACN) has made explicit the values that form
      the cornerstone of professional nursing: altruism, autonomy, human dignity,
      integrity, and social justice. In this article, the authors explore the
      interconnections between values explicated by the AACN and nursing practices and
      policies. The authors draw on work in the field of pain management, cultural
      competency, and harm reduction as exemplars of this interconnection. The authors
      propose that through political action, nurses can strive for congruence between
      their professional values, practice, and policies and subsequently effect change
      and improve health outcomes.

PMID- 16443957
TI  - The health bus: healthcare for marginalized populations.
AB  - The Health Bus, an innovative outreach program, serves the marginalized
      population of a large Canadian city. In this article, a needs
      assessment/evaluation study of its services is discussed. Barriers to mainstream
      healthcare and solutions are examined. This study was qualitative, descriptive,
      and exploratory and surveyed 58 client volunteers of the program through
      semistructured interviews and focus groups. Thematic analysis of data was carried
      out. The Health Bus was found to provide basic healthcare and supplies
      effectively. Clients value respectful treatment, competency of healthcare
      professionals, and accessibility, whereas disrespectful treatments and lack of
      transportation are barriers to mainstream healthcare. A conclusion of this study
      is that Health Bus services should be expanded with clients' input. Mainstream
      institutions need flexibility and a change in attitudes toward the marginalized.

PMID- 16443958
TI  - The influence of a change in medicare reimbursement on the effectiveness of stage
      III or greater decubitus ulcer home health nursing care.
AB  - This study was designed to describe and evaluate the influence of a change in a
      Medicare reimbursement on the effectiveness of home health nursing care for stage
      III or greater decubitus ulcer patients. This health policy originated from the
      Balanced Budget Act (BBA) of 1997 and took its full effect with initiation of the
      Prospective Payment System (PPS) on October 1, 2000. A quantitative quasi
      experimental design used OASIS data from the state of Virginia to evaluate 555
      stage III or greater decubitus ulcer patients, age 65 or older. Comparisons were
      investigated between pre-PPS, 2000, and post-PPS, 2001, outcomes related to
      reported ulcer healing, lengths of stay, and discharge disposition. Results
      demonstrated significant differences for the outcomes studied. In addition,
      sanitation, ulcer healing, and discharge disposition were linked as predictors
      for length of stay. Results demonstrated that PPS has affected nursing care
      effectiveness for stage III or greater decubitus ulcer home health patients.

PMID- 16443959
TI  - The culture of safety.
AB  - A new paradigm is emerging as a result of the Institute of Medicine reports on
      medical errors. The Joint Commission on Accreditation of Healthcare
      Organizations, state licensing boards, academic institutions, and health care
      businesses are considering their missions and goals vis-a-vis a culture of
      patient safety. The author presents three examples that converge to indicate that
      the culture of safety represents a paradigm shift for the education, delivery,
      funding, and evaluation of health and medical care. The system, not the
      individual, must be recognized as the problem; reprimanding the person who
      committed an error is not a solution. Health care delivery systems that reduce
      this potential for error must be created.

PMID- 16443960
TI  - Mid-career opportunity for nurses: learning and growing through a health policy
      internship.
AB  - This article shares the experience and insight gained from a mid-career policy
      internship offered through the National Academy of Social Insurance. The author
      is a nursing doctoral student who interned on veterans' long-term care projects
      with the Health Care Team at the Government Accountability Office in Washington,
      D.C. As the average age of nurses continues to rise and society faces nursing
      shortages, new opportunities and solutions must be considered to keep aging
      nurses in the workforce. A mid-career internship is a very real option that will
      benefit health policy organizations, the nursing community, and aging nurses.

PMID- 16443961
TI  - Transcendent pluralism and the influence of nursing testimony on environmental
      justice legislation.
AB  - Environmental justice is an important issue affecting health disparities. Using
      the framework of transcendent pluralism, this article describes nursing actions
      and research in a legislative coalition for an environmental justice bill. Two
      descriptive studies are conducted: a focus group with six legislative aides and
      an evaluation of a nursing presentation given to 10 Massachusetts state
      legislators. Pretest and posttest results showed a small but significant increase
      in the legislators' disposition toward the bill; the mean score increased from
      5.4 to 5.9 (p = .037). Legislators perceived nurses as lobbying more for nursing
      profession issues than general health issues (score of 6.3 vs. 4.6; p = .009).
      Guidelines for lobbying that emerged from the data are included. The author
      argues that nursing knowledge should play a vital role in public policy and that
      nurses need to broaden their efforts beyond professional issues to the larger
      issues that influence a healthy human society.

PMID- 16443964
TI  - Advanced nursing training in health policy: designing and implementing a new
      program.
AB  - Although the nursing profession has a growing role in the health policy arena,
      the rapidly changing health care environment means that clinicians need a
      sophisticated understanding of health policy. Nurses are assuming leadership
      roles in advocacy, research, analysis, and policy development, implementation,
      and evaluation, contributing to a growing need to educate nurses to specialize in
      health policy research and analysis. This article provides an overview of a new
      master's and doctoral educational program specializing in health policy for
      advanced practice nurses who are culturally diverse and sensitive to issues of
      diversity. The program, currently in its third year of operation at the
      University of California San Francisco, School of Nursing, is addressing the gap
      in nursing education and practice expertise in health policy. The program is
      supported through funding by the Department of Health and Human Services Health
      Resources and Services Administration, Advanced Nurse Training program.

PMID- 16443963
TI  - State policies regarding nursing delegation and medication administration in
      child care settings: a case study.
AB  - Medication administration is an essential component of quality child care, and
      nurses play a central role in assuring high-quality training of child care
      providers. Through key informant interviews and review of public documents, this
      case study explored the development of state statutes and regulations for
      medication administration training of child care providers in the state of
      Connecticut, nursing liability issues related to the definition of this activity,
      and the role of the Connecticut State Board of Examiners for Nursing. This
      article also examines the interpretation of the nursing role within this context
      as delegation versus professional activity and the impact of such designation on
      nursing practice, child care providers' access to medication administration
      training by nurses, and children's health status in child care settings. As a
      result of this case study, the Connecticut State Board of Examiners for Nursing
      revised its policies, demonstrating an exemplar linkage among research, practice,
      and policy.

PMID- 16443965
TI  - Policy perspectives of major nursing organizations. Interview by David M.
      Keepnews.
AB  - Understanding the roles of interest groups is an important element of examining
      policy change. There are a number of interest groups that affect the policy
      environment for nursing and that shape the profession's impact on health policy.
      This article is the first of a series featuring interviews with executive
      directors/chief executive officers of three major nursing organizations, focusing
      on their policy priorities and how these priorities are determined. The three
      organizations featured in this article are the American Nurses Association (ANA),
      the American Association of Colleges of Nursing (AACN) and the National Council
      of State Boards of Nursing (NCSBN).

PMID- 16443966
TI  - Disclosure of medical errors: ethical considerations for the development of a
      facility policy and organizational culture change.
AB  - The Institute of Medicine report, To Err Is Human: Building a Safer Health
      System, has spurred public concern over hospitals' ability to deliver safe care.
      The health care industry continues to struggle to address these concerns. These
      efforts have driven the growing expectation that health care practitioners or
      systems disclose unanticipated outcomes to patients and family members. Although
      the tort system has been cited as an impediment to medical error disclosure, some
      organizations and systems have successfully implemented policies calling for full
      disclosure of errors and unanticipated outcomes. However, most organizations have
      yet to develop policies concerning error disclosure. This article provides an
      overview of error disclosure and a model framework for an error disclosure
      policy. The ethical principle of respect for patient autonomy is emphasized as
      the driving force in developing an institutional disclosure policy and changing
      the organizational culture to one that supports development and implementation of
      such a policy.

PMID- 16443967
TI  - Assessing the policy environment.
AB  - This article proposes a basic framework for assessing the policy environment.
      Environment is a key concept in nursing's much-discussed "metaparadigm," but the
      policy environment is rarely considered. Too often, bedside nurses do not
      recognize the policy dimensions of clinical practice issues. Yet nursing
      assessment involves identifying and appraising aspects of patients' situations
      that are salient to their responses to actual or potential health problems.
      Policy may be such a salient factor, as it shapes the physical aspects of
      patients' surroundings; the relationships possible between practitioners and
      patients; the institutions in which health care is offered; and, on a broader
      scale, the prospects for global survival. This article proposes a question-based
      framework for clinical practice nurses to use in assessing the policy
      environment.

PMID- 16443968
TI  - The Bush Administration's record on nursing issues.
AB  - The article addresses a number of initiatives taken in 2005 by the Bush
      Administration to address nursing issues. Summaries are provided of the
      investments in the Nurse Reinvestment Act, Financial Aid, access issues
      (including expanded community health centers), costs (including medical liability
      reform), information technology and the revised fair labor standards. Finally,
      the author concludes with rationale for complete workforce and workplace system
      redesign and the need for advanced practice nurses to engage in full scope
      practice without artificially imposed boundaries.

PMID- 16443969
TI  - Putting policy theory to work: tobacco control in California.
AB  - Policy theory provides a useful lens for nurses evaluating how problems are
      understood and responded to within the policy arena. This article examines and
      critiques the agenda-setting model offered by John Kingdon. Furthermore, the
      theory is applied to the issue of tobacco control in the state of California,
      suggesting policy solutions and strategies to achieve their placement on the
      policy agenda. Strategies and techniques that may be useful to nurse policy
      champions are elucidated.

PMID- 16443970
TI  - Reading from ratios.

PMID- 16443971
TI  - Developing a new resource on international nurse migration: the international
      centre on nurse migration.
AB  - A new collaborative project on nurse migration was recently launched by the
      International Council of Nurses and the Commission on Graduates of Foreign
      Nursing Schools. This collaboration, the International Centre on Nurse Migration,
      guided by the principles of ethical recruitment and equitable treatment of
      migrating nurses, focuses on promoting, collecting, creating, and disseminating
      data and information on nurse migration; acting as a resource center; tracking
      trends and patterns of global health care workforce migration; analyzing policy;
      generating policy options; advocating for sound policy concerning nurse
      migration; promoting, undertaking, and disseminating research; providing
      consultant and expert advice; and offering continuing education about migration.

PMID- 16443972
TI  - Projections and trends in RN supply: what do they tell us about the nursing
      shortage?
AB  - This article presents an analysis of trends in the supply of RNs. When weighted
      for population growth, the U.S. Department of Health and Human Services' 2002
      projection of future RN shortages indicates a more imminent and stronger decline
      in RN supply than initially presented. Analysis of national RN survey data from
      1977 to 2000 finds recent decreased gains and increased losses from the RN
      license pool, a decline in RNs working or looking for work in nursing, and RN
      supply shifts away from bedside nursing. Policy implications to address these
      trends include regulatory/legislative and incentive approaches aimed at improving
      education and employment.

PMID- 16443973
TI  - Trends in nurse overtime, 1995-2002.
AB  - Nurses and their advocates have expressed concern about increasing use of
      overtime in hospitals, but systematic data on trends in the amount of overtime
      worked by nurses has been lacking. Using data on New York hospitals, we find that
      overtime increased 51% between 1995 and 2002, from 3.9% of total hours to 5.9%.
      Most of the increase occurred after 1997, and the rate of overtime use leveled
      out from 2001 to 2002. Overtime increased more in nongovernment unionized
      hospitals and nonteaching hospitals, but the wide variation in changes in
      overtime suggests there is substantial management discretion in using overtime to
      address fluctuations in census and staffing.

PMID- 16443974
TI  - Nurses' work environment perceptions when employed in states with and without
      mandatory staffing ratios and/or mandatory staffing plans.
AB  - Multiple stakeholders have sought regulatory and nonregulatory strategies to
      address nursing workforce and patient safety concerns. This study examines
      differences in nurses' work environment perceptions. Approximately 4,000 nurses
      employed in 10 states provided their perceptions of key characteristics of their
      work environment using the Individual Workload Perception Scale. Univariate
      statistics were used to characterize mean values of the nurses' work environment
      perceptions by state of employment and whether these perceptions changed if
      employed in states with versus without mandatory staffing ratios and/or mandatory
      staffing plans. This study provides preliminary evidence that mandatory staffing
      plan legislation may be linked with the most positive nurse work environment
      perceptions when compared with implementation of mandatory staffing ratios or no
      workforce regulation. Based on this preliminary observation, further analysis
      comparing the relative benefits and costs of workforce regulation may be
      warranted.

PMID- 16443975
TI  - Impact of California's licensed nurse-patient ratios on unit-level nurse staffing
      and patient outcomes.
AB  - This article presents the first analysis of the impact of mandated minimum
      staffing ratios on nursing hours of care and skill mix in adult medical and
      surgical and definitive-observation units in a convenience sample of 68 acute
      hospitals participating in the California Nursing Outcomes Coalition project.
      Findings, stratified by unit type and hospital size, reveal expected changes as
      hospitals made observable efforts toward regulatory compliance. These data cannot
      affirm compliance with ratios per shift, per unit, at all times; however, they
      give evidence of overall compliance. Assessment of the impacts of the mandated
      ratios on two common indicators of patient care quality, the incidence of patient
      falls and the prevalence of pressure ulcers, did not reveal significant changes
      despite research linking nurse staffing with these measures. These findings
      contribute to understanding unit level impacts of regulatory staffing mandates
      and the preliminary effect of this legislation on core quality of care
      indicators.

PMID- 16443976
TI  - Passing a smoke-free law in a pro-tobacco culture: a multiple streams approach.
AB  - This article describes a case study of the policy development and political
      decision-making process involved in the enactment of Lexington, Kentucky's smoke
      free law. The multiple streams framework is used to analyze the development of
      the law in a seemingly unlikely and challenging political environment. Proponents
      developed a dissemination research plan targeted at policy makers and the public
      to demonstrate the need for a comprehensive law. The existence of a strong
      coalition of health care providers and health care systems including the board of
      health, as well as long-standing tobacco control expertise and a strong legal
      team, were essential ingredients for success. A deliberate strategy to expose the
      tobacco industry was effective in preparing policy makers for the opponents'
      policy arguments. As expected, a hospitality industry association was formed to
      oppose the ordinance, resulting in a legal challenge that delayed enactment of
      the law.

PMID- 16443977
TI  - Adult ambulatory care visits to nurses and physicians: methodological limitations
      of the medical expenditure panel survey data.
AB  - The 1997 Medical Expenditure Panel Survey (MEPS) data report that approximately
      80 million adult ambulatory visits are made to nursing personnel. Adults who
      visit nursing personnel and who visit physicians are similar with regard to sex
      and income. As compared to nursing personnel, physician visits are longer and
      more likely to involve diagnosis or treatment. Older adult visits (ages 65 to 90)
      to nursing personnel are significantly longer than the visits of younger adults.
      As compared to physician visits, nursing personnel visits are significantly more
      likely to be characterized as "other" for all adults and especially for older
      adults. Although these findings suggest important differences between physician
      and nurse ambulatory care visits, the undifferentiated use of the term nurse and
      the significant percentage of uncharacterized visits to nursing personnel signal
      serious deficiencies in the MEPS data in exploring nonphysician ambulatory care.

PMID- 16443978
TI  - A nursing PhD specialty in health policy: University of Massachusetts Boston.
AB  - This article describes the Nursing PhD Program specialty in health policy
      conceived and developed at the University of Massachusetts Boston. The rationale
      for a specialty in health policy is that nurses have valuable knowledge and a
      unique perspective of the health care system. Nurses belong to the largest group
      of health care providers and are the providers that spend the most time with
      patients. The nursing profession has a responsibility to help assure members of
      society have access to safe and effective quality health care. As a group, nurses
      need to be politically savvy to translate their knowledge and perspective to
      benefit society. Nurses need to direct their attention to understanding issues
      and policy arguments and to contribute to policy discussion with reasoned
      arguments and objectivity. The PhD program at the University of Massachusetts
      Boston prepares nurses as policy analysts, researchers, and educators who will
      positively contribute to the health of society.

PMID- 16443979
TI  - Practice patterns and potential solutions to the shortage of providers of older
      adult mental health services.
AB  - Little is known about the contribution of advanced practice nurses (APNs) to the
      mental health care of older adults. This study describes mental health services
      to older adults by APNs compared with primary care physicians, psychiatrists,
      psychologists, and social workers. The study uses a retrospective, cross
      sectional design with a 5% national sample of 1999 Medicare outpatient claims.
      Bivariate statistics and multinomial logit models were used to determine
      differences among these mental health providers. A small proportion of the
      nationally available providers (10.4%) submitted claims for mental health
      services rendered to older adults. APNs, psychiatrists, and primary care
      physicians care for a disproportionate number of rural and poor older adults with
      complex medical/psychiatric needs compared with psychiatrists, psychologists, and
      social workers. APNs seem to be an untapped resource for providing mental health
      services to older adults. Health policy reform is needed to remove barriers to
      meet mental health care needs.

PMID- 16443980
TI  - Policy perspectives of major nursing organizations, part II. Interview by David M
      Keepnews.
AB  - Understanding the roles of interest groups is an important element of examining
      policy change. There are a number of interest groups that affect the policy
      environment for nursing and that shape the profession's impact on health policy.
      This article, the second of a two-part series, presents interviews with executive
      directors and chief executive officers of major nursing organizations about their
      organizations' policy priorities and policy-related activities. Included in this
      article are the American Organization of Nurse Executives, the National League
      for Nursing, Sigma Theta Tau International, and the National Black Nurses
      Association.

PMID- 16443981
TI  - Health policy--a nursing specialty?

PMID- 16443982
TI  - Truck driver hours of service regulations: the collision of policy and public
      health.
AB  - This article examines the policies related to truck driver hours of service
      regulations that affect occupational and public health and safety. The
      interaction of the nature of truck driving, labor practices and deregulation of
      the trucking industry, and the evolution of the current regulations are
      presented. The work of advocacy coalitions and legal action related to this issue
      is described. Possible policy alternatives and recommendations are presented. The
      article supports the position that although federal government regulators attempt
      to promulgate regulations based on current circadian science, the regulations are
      ineffective as stand-alone measures. Labor policies and practices must foster a
      work environment that facilitates sleep and safe driving performance. Advocacy by
      nurses on this issue continue the rich tradition of public health nursing. Nurses
      may benefit from the study of truck driver hours of service regulation as
      recommendations limiting their own hours of service are being considered and
      legislated.

PMID- 16443983
TI  - Nurse and client perceptions of home health wound care effectiveness after a
      change in Medicare reimbursement.
AB  - The purpose of this study was to begin to explore client and nurse perceptions
      related to how a change in a Medicare reimbursement, Prospective Payment System
      (PPS), affects home health care. The target population included home health
      clients with stage III or greater decubitus ulcers, age 65 years or older. Six
      Virginia home health agencies were randomly selected. From those sites, all 39
      charts that met population criteria were accessed and analyzed, and then 16 care
      recipients were purposely selected. In addition, 26 home health nurses with pre-
      and post-PPS experience were purposefully selected. Semistructured, audiotaped
      interviews were conducted, transcribed, and analyzed using thematic content
      analysis. Results demonstrated PPS adaptive behavior and an increase in use of
      education and family caregivers related to wound care. Themes that emerged
      included professional competence, caregiver as key, and sense of support.
      Perceptions emphasize the necessity for resource management, collaboration, and
      patient advocacy.

PMID- 16443984
TI  - Policy predictors of participation in adult tobacco cessation programs.
AB  - This article examines the effect of tobacco cessation treatment factors and
      environmental, structural, and client factors on participation in tobacco
      cessation programs among adults in a tobacco growing state. A pooled time series
      cross-sectional research design was used to analyze the primary and secondary
      data collected at the population level (N = 140 Health Department Service Areas;
      HDSA). Results indicated that for every cessation program added, there would be
      an increase in participation of 4 adults per 10,000 smokers, and for every 1.00
      dollar per capita spent on counteradvertising, there would be an increase in
      participation of 26 adults per 10,000 smokers. Local health departments need to
      initiate or increase counteradvertising, targeting younger adults and HDSAs with
      higher per capita tobacco production; enhance marketing efforts for cessation;
      and increase the number of cessation programs offered by HDSAs to as many as are
      feasible and affordable.

PMID- 16443985
TI  - Policy implications of the relationship of sick leave benefits, individual
      characteristics, and fatigue to employment during radiation therapy for cancer.
AB  - Undergoing a course of radiation therapy for cancer does not preclude the need to
      work during treatment. This study examines the impact of sick leave benefits,
      individual characteristics, and fatigue on employment during radiation therapy.
      The conceptual model of nursing and health policy (CMNHP) and the Piper
      integrated fatigue model (IFM) guided this study. Seventy-seven study
      participants receiving radiation therapy were recruited from one community
      hospital. The study employed a prospective, longitudinal design. Data were
      collected at baseline prior to starting radiation therapy, weekly during
      treatment, and at the 1-month follow-up visit. Only 49% of study participants had
      paid sick leave benefits available at the start of radiation. Age, pain, gender,
      side effects, availability of sick leave benefits, and fatigue were associated
      with work along the trajectory of radiation therapy. Further research addressing
      the impact of paid leave policies on the relation between work and cancer-related
      fatigue is warranted.

PMID- 16443986
TI  - The conceptual model for nursing and health policy revisited.
AB  - A conceptual model of nursing and health policy was proposed by the authors in
      2001. Revisions in the model have been made, and the model has been used to guide
      the evolution of a nursing doctoral program and doctoral dissertation research.
      The revised model provides a framework for analysis and evaluation of public,
      organizational, and professional policies influencing the quality, cost, and
      access to nursing and other health care services, as well as for nursing
      discipline specific and health services research at any one of four interacting
      levels: Level 1--efficacy of nursing practice processes; Level 2--effectiveness
      of nursing practice processes and effectiveness and efficiency of health care
      delivery subsystems; Level 3--equity of access to effective and efficient nursing
      practice processes and efficient nursing practice delivery systems, and equity in
      distribution of costs and burdens of care delivery; Level 4--justice and the
      social changes and market interventions addressing equity.

PMID- 16443987
TI  - North Carolina Center for Nursing health policy fellowship: a strategy for
      developing nursing leaders for the future.
AB  - In the midst of ongoing concern about succession planning to develop the next
      generation of nursing leaders, the profession cannot afford to overlook
      succession planning in regard to the next generation of nurse leaders in health
      policy. This article describes a project of the North Carolina Center for Nursing
      that provides a fellowship in state-level health policy for North Carolina nurses
      who have completed a graduate level health policy course. Policy fellows are
      exposed to health policy analysis through the public policy arena, regulatory and
      administrative arenas, and organizational and institutional arenas. As part of
      this journey, all major state stakeholders in health policy are involved in the
      mentoring process. The North Carolina Center for Nursing Health Policy Fellowship
      is described here as a potential model related to policy initiatives in other
      states.

PMID- 16443988
TI  - Performance evaluation for diversity programs.
AB  - This policy paper addresses the problem of underrepresentation of minorities in
      the health care professions. Projections are that by 2050 minorities will
      represent 49% of the U.S. population. Several notable reports suggest that the
      health care of underrepresented minorities is improved when providers of similar
      ethnic and racial backgrounds provide the care. However, minority representation
      in the health care professions has not kept pace with the increase of minorities
      in the population. A variety of groups (federal, state, private, and health
      professional educational institutions) have provided billions of dollars toward
      increasing the number of underrepresented minority health care providers.
      However, the effectiveness of these programs is not readily evident. Therefore,
      we recommend comprehensive evaluations of programs funded to increase diversity
      in the health professions and the development of a Minority Health Care
      Professionals Center to assume accountability for monitoring programs that
      receive funding to increase the number of underrepresented minority health care
      providers.

PMID- 16443989
TI  - Low-income housing policy and socioeconomic inequalities in women's health: the
      importance of nursing inquiry and intervention.
AB  - Decent, affordable housing is the building block of healthy neighborhoods.
      Housing characteristics not only shape the quality of life in communities but
      also affect individual and family health. The structural and social aspects of
      housing have a significant impact on the health of individuals and populations.
      Early public health nursing pioneers such as Lillian Wald and Jane E. Hitchcock
      understood the adverse impact of substandard housing on population health and
      incorporated advocacy for housing and other social policy reforms as an integral
      aspect of their nursing interventions. Contemporary nursing literature, however,
      is lacking in its critical examination of relationships between housing and
      health. This article presents historical and current issues in low-income housing
      policy, discusses how low-income housing policy has contributed to social
      inequalities in health, and advocates for the importance and inherent value of
      nursing inquiry and intervention in this area.

PMID- 16443990
TI  - Emergency contraception for sexual assault victims: an advocacy coalition
      framework.
AB  - A bill was introduced into the Tennessee legislature in the 2005 session that
      would require emergency departments to offer and dispense emergency contraception
      to sexual assault survivors who are at risk of pregnancy. Several advocacy groups
      collaborated to form the Women's Health Safety Network for the purpose of
      communicating as one voice. The advocacy coalition framework of policy
      development is applied to the political system and is used as a model to discuss
      issues impacting policy development for this particular bill. Key actors,
      proponents, and opponents to this bill are presented along with constraints to
      policy acceptance. The challenge for emergency contraception advocates on a state
      and national level is to keep the focus on public health science, the health and
      well-being of women, and out of the abortion debate.

PMID- 16443991
TI  - Early evidence on California staffing ratios should be interpreted with caution.

PMID- 16443993
TI  - Where is the family in family interventions?

PMID- 16443994
TI  - The "hard spots" of family nursing: connecting across difference and diversity.
AB  - The focus of this discussion is how nurses might more effectively work within the
      "hard spots" of family nursing to connect across difference. Taking a pragmatic
      stance toward knowledge, the practical consequences of ideas and theories
      informing definitions of family and family nursing practice are examined. The
      authors propose that the provision of competent, ethical, and culturally safe
      nursing care could be greatly enhanced by a relational view. In particular it is
      suggested that understanding family as a relational experience, understanding
      nursing and culture as relational processes and conceptualizing difference as a
      basis for connection can provide a foundation for more effectively working across
      differences. Using this relational view the authors outline processes that have
      the potential to foster more equitable, just, and compassionate family nursing
      practice.

PMID- 16443995
TI  - Family identity: black-white interracial family health experience.
AB  - The purpose of this interpretive descriptive study was to describe how eight
      Black-White couples with school-aged children constructed their interracial
      family identity through developmental transitions and interpreted race to their
      children. Within and across-case data analytic strategies were used to identify
      commonalities and variations in how Black men and White women in couple
      relationships formed their family identities over time. Coming together was the
      core theme described by the Black-White couples as they negotiated the process of
      forming a family identity. Four major tasks in the construction of interracial
      family identity emerged: (a) understanding and resolving family of origin chaos
      and turmoil, (b) transcending Black-White racial history, (c) articulating the
      interracial family's racial standpoint, and (d) explaining race to biracial
      children across the developmental stages. The findings guide family nurses in
      promoting family identity formation as a component of family health within the
      nurse-family partnership with Black-White mixed-race families.

PMID- 16443996
TI  - Duality in context: the process of preparedness in communicating with at-risk
      children.
AB  - The goal of this study was to explore the cultural meaning of parent-child
      communication behaviors in inner-city children at risk for common behavioral
      problems. Following participation in a preventive intervention called Insights
      Into Children's Temperament, 40 parents of first and second-grade children were
      interviewed. The data were analyzed using a constant comparative method derived
      from grounded-theory techniques. Findings indicate that a complex communication
      process was used by parents with their at-risk inner-city school-age children.
      The immediacy of safety concerns for the child, the child's temperament, and the
      current parental state informed the choice of communication behaviors chosen by
      the parent. The ultimate goal of communication for these participants was to
      equip their children with tools to assist them to safely navigate their school
      and community environments. Participants also offered several recommendations
      that could be useful for practitioners and researchers to incorporate into their
      work with inner-city families.

PMID- 16443997
TI  - Families discovering asthma in their high-risk infants and toddlers with severe
      persistent disease.
AB  - Interpretive phenomenology was used to discover the earliest experiences of
      families of children younger than 4 years hospitalized for severe persistent
      asthma. The children who were African American or Latino and living in poverty
      were at highest risk of morbidity and mortality. Three families with distinctly
      varied responses to early symptoms were chosen from an investigation of 11
      families for this study. Each gave three home interviews and participated in home
      observations. All families experienced life-changing responses to their
      children's distressed breathing. All had experienced asthma in themselves or
      others that shaped their beliefs and management patterns. Family experiences
      prior to and following diagnosis are discussed. Findings suggest that
      understanding these experiences and respecting families' earliest responses will
      help clarify established family management patterns for severe asthma in infants
      and toddlers and will enhance the ability of providers to guide the care of these
      families and children.

PMID- 16443998
TI  - Family strategies for supporting involvement in meaningful activity by persons
      with dementia.
AB  - Involvement in meaningful activity may be helpful for those with dementia,
      although it is a poorly understood phenomenon among those living in the community
      with family members. An interpretive phenomenological study was conducted with
      eight families to determine how family members support involvement in activity of
      persons with dementia and what it means to families. Repeated individual
      interviews were conducted with the person with dementia and a family member; they
      were asked to tell stories about their usual activities, to consider the impact
      of the dementia on everyday life and what they did to cope with difficulties.
      They were also observed taking part in everyday activities. Analysis revealed
      three strategies used by families to support activity: (a) reducing demands, (b)
      guiding, and (c) accompanying. These strategies allowed families to sustain
      meaning for both the person with dementia and the family itself. Significance for
      practice and ideas for future research are discussed.

PMID- 16443999
TI  - Magnesium profile in autism.
AB  - The aim of the present study was to determine and compare plasma and erythrocyte
      concentrations of magnesium in 12 autistic children (10 boys, 2 girls), 17
      children with other autistic spectrum disorders (14 boys, 3 girls), 5 girls with
      classic Rett syndrome, and 14 normal children (7 boys, 7 girls) of the same age.
      No differences in intracellular Mg were found between controls and pathological
      subjects; however, autistic children and children with other autistic spectrum
      disorders had significantly lower plasma concentrations of Mg than normal
      subjects (p=0.013 and p=0.02, respectively). Although our study population was
      small, we conclude that children with autistic spectrum disorders require special
      dietary management. If these cases are diagnosed at an early stage, they can be
      helped through diet.

PMID- 16444000
TI  - Effects of nutrition on zinc, folic acid, and vitamin B12 levels during
      pregnancy.
AB  - In this article, we report the results of a case control study carried out on 290
      Turkish pregnant women at 5-24 wk of gestation to determine their zinc, folic
      acid, and vitamin B12 levels in relation to their nutritional and socioeconomic
      status. The women were divided into two groups (n=145 each), depending on the
      stage of gestation. Group I consisted of women in the first trimester of
      gestation; those in the second trimester were allocated into group II. Twenty
      five age-matched, healthy nonpregnant women were selected as controls. The
      nutritional status of the subjects was determined by means of a survey. Based on
      this, the women were subdivided into three subgroups: malnourished (PN),
      moderately nourished (MN), and well nourished (WN). Also from the survey, the
      socioeconomic status was classified as good (G) or bad (B). A statistically
      significant decrease on zinc and folic acid was observed in group I women, as
      their socioeconomic status worsened. In group II, zinc decreased only in the PN
      and MN subgroups, p<0.001. The folic acid and vitamin B12 levels did not change
      significantly during the second trimester of gestation in all subgroups.
      Regarding zinc, nutrition, or dietary habits are more relevant than socioeconomic
      status, but poor nutrition affects folic acid levels only during the first
      trimester of gestation.

PMID- 16444001
TI  - Long-term changes in trace elements in patients undergoing chronic hemodialysis.
AB  - Although the connection between aluminum intoxication and dialysis dementia was
      identified in the 1980s, understanding of trace element imbalances in
      hemodialysis patients is as yet incomplete. Recent application of newer
      inductively coupled plasma-mass spectrometry (ICP/MS) techniques has resulted in
      renewed study of this population. We used ICP/MS to evaluate serum concentrations
      of Cu, Se, Zn, Mn, and Ni in a relatively large population of hemodialysis
      patients compared with healthy age-matched controls. Comparisons were also done
      by duration of hemodialysis treatment to see whether length of treatment
      correlates with severity of imbalance. Patients had significantly lower
      concentrations of the three elements Se, Zn, and Mn. Patients had significantly
      higher concentrations of Ni, and there was a positive correlation between
      duration and severity of imbalance for this one element. There was no difference
      in Cu concentrations between patients and controls. Our findings confirm relative
      Ni excess and deficiencies of Se, Zn, and Mn in hemodialysis patients,
      documenting the value of ICP/MS in research work on trace element imbalances as
      well as clinical monitoring of individual patients.

PMID- 16444002
TI  - Correlation of serum trace elements and melatonin levels to radiological,
      biochemical, and histological assessment of degeneration in patients with
      intervertebral disc herniation.
AB  - The aim of our study was to assess the blood concentrations of some trace
      elements and melatonin (MLT) in patients with intervertebral disc herniation
      (IDH) and to investigate the interaction of histological and biochemical
      degeneration findings with aging. The present study was carried out on 13
      subjects (8 women and 5 men) diagnosed with IDH. They were divided into three
      groups according to their ages. Nighttime serum MLT, zinc (Zn), and magnesium
      (Mg) levels were determined in all patients. In addition, computed tomography
      (CT) scan of the brain and magnetic resonance imaging examination of the lumbar
      spine were obtained in this study. The Zn level and Zn/Mg ratio showed a decline
      in patients with IDH with aging, whereas the serum Mg level and tissue
      hydroxyproline content increased. A positive correlation between serum Zn and MLT
      concentrations was found (r=0.104, p=0.734). In addition, there was a positive
      correlation between serum Zn level and Zn/Mg ratio (r=0.835 and p<0.01), and a
      negative correlation between serum Mg level and Zn/Mg ratio (r=-0.571, p<0.05).
      On CT study, both volume percentage of calcified pineal gland and density of
      calcification were found to increase progressively with advancing age. The
      results of semiquantitative evaluation of disc tissues of patients with IDH for
      histological degeneration findings showed that 66.7% of discs treated had slight
      degeneration in younger age group, but 75.0% and 100% of discs had moderate or
      marked degeneration in older age groups. Our data indicated that there is a close
      relationship between MLT and Zn or Mg levels in the serum samples of patients
      with IDH, and the levels of these elements might be affected by the presence of
      degeneration process and serum MLT level, or vice versa.

PMID- 16444003
TI  - Copper, zinc, iron, and manganese accumulation in cattle from asturias (northern
      Spain).
AB  - Monitoring levels of mineral concentrations in animal tissues is important for
      assessing the effect of contamination on animal health and safety of animal
      origin products in human nutrition. This study evaluated the levels of certain
      trace elements (copper, zinc, iron, and manganese) in cattle from an industrial
      and mining region in the north of Spain (Asturias). Samples of 312 animals aged 9
      12 mo were collected from the whole region and analyzed after acid digestion
      using atomic absorption spectrophotometry (AAS). The geometric mean
      concentrations obtained per wet weight for the liver, kidney, muscle, and blood
      were 34.3 mg/kg, 4.04 mg/kg, 1.65 mg/kg, and 0.651 mg/L for copper, respectively,
      and 38.5 mg/kg, 23.0 mg/kg, 47.0 mg/kg, and 2.44 mg/L for zinc, respectively. For
      iron, blood was not analyzed and results were 96.2 mg/kg, 105 mg/kg, and 56.0
      mg/kg for the liver, kidney and muscle, respectively. For manganese, only the
      liver and kidney were analyzed, and the results were 3.11 mg/kg and 1.19 mg/kg,
      respectively. There was no evidence of an accumulation of toxic levels of trace
      metals in Asturian cattle. Females accumulated more iron in the liver (p<0.001,
      F<I->1,310=18.4) and the kidney (p<0.001, F<I->1,310=13.5) and more manganese in
      the liver (p<0.01, F<I->1,310=9.55) than males.

PMID- 16444004
TI  - Effect of selenium supplementation on thyroid hormone levels and selenoenzyme
      activities in growing lambs.
AB  - The aim of the present study was to evaluate the effects of selenium
      supplementation on thyroid hormone metabolism and selenoenzyme activities in
      lambs. Twelve 20-d-old male lambs were assigned to one of two diets: A (0.11 ppm
      Se) and B (supplemented with 0.2 ppm selenium as sodium selenite). Blood samples
      were collected weekly for the determination of T3, T4, and selenium levels. The
      response to thyrotropin-releasing hormone (TRH) challenge was estimated at the
      11th and 20th wk. Animals were slaughtered at wk 20 and tissues were collected
      for enzyme determination. Plasma selenium concentration was significantly higher
      in supplemented lambs (p<0.001). Plasma T3 and T4 levels remained similar in both
      groups. Type I deiodinase activity (ID-I) was decreased in the liver (p<0.05) and
      increased in the pituitary (p<0.01) of supplemented animals. No ID-I activity was
      detected in the thyroid. Pituitary type II deiodinase activity (ID-II) remained
      unchanged. The response to TRH challenge did not differ between the two groups
      for both challenges, but in group B, the second TRH challenge (20th wk) resulted
      in a significantly higher T3 response compared to the first one (11th wk)
      (p<0.05). In conclusion, the lack of effects of Se supplementation on thyroid
      hormone metabolism demonstrates that enzyme activity is homeostatically
      controlled and selenium is incorporated in that order to ensure the maintenance
      of thyroid hormone homeostasis.

PMID- 16444005
TI  - Cystathionine gamma-lyase contributes to selenomethionine detoxification and
      cytosolic glutathione peroxidase biosynthesis in mouse liver.
AB  - We earlier found that seleno-l-methionine (L-SeMet) as a food source of selenium
      (Se) is directly converted to methylselenol (CH3SeH), alpha-ketobutyrate, and
      ammonia by the mouse hepatic cystathionine gamma-lyase. The purpose of this study
      was to clarify the biological role of cystathionine gamma-lyase in Se
      detoxification and cytosolic glutathione peroxidase (cGPx) biosynthesis because
      another metabolic pathway to CH3SeH via seleno-l-cystathionine and seleno-l
      cysteine (l-SeCyH) from l-SeMet has been shown by several enzymatic reactions.
      When mice were treated with either toxic doses of l-SeMet or a Se-deficient diet,
      the cystathionine gamma-lyase activity for l-SeMet was invariable, suggesting
      that this enzyme was effective in both detoxification and biotransformation of
      Se. Concerning Se biotransformation into cGPx, production of H2Se as the possible
      precursor was not observed by the in vitro reaction of the liver cytosol with
      CH3SeH. When l-SeMet was administered at the nutritional dose to mice fed a Se
      deficient diet, levels of both cGPx mRNA and cGPx protein were significantly
      restored. This recovery was not comparatively suppressed by coadministration of
      periodate-oxidized adenosine, an inhibitor of S-adenosylhomocysteinase, where the
      conversion of l-SeMet to l-SeCyH is inhibited. However, the recovery was strongly
      suppressed when propargylglycine, an inhibitor of cystathionine gamma-lyase that
      catalyzes the alpha,gamma-elimination reaction of both l-SeMet and seleno-l
      cystathionine, was treated. These results suggest that cystathionine gamma-lyase
      is a notable enzyme in SeMet metabolism and that CH3SeH produced by the enzymatic
      reaction is utilized for cGPx biosynthesis.

PMID- 16444006
TI  - Microarray analysis of selenium-depleted and selenium-supplemented mice.
AB  - Nutritional selenium deficiency is associated with Keshan disease in humans and
      white muscle disease in ruminant livestock. In this study, mice were fed a
      selenium-deficient diet for three generations. Female mice from the third
      depleted generation of these mice were given water containing either no added
      selenium or 0.1 or 1.0 ppm selenium as sodium selenate; DNA microarrays were used
      to compare gene expression in the muscle from mice fed the selenium diets to that
      from mice remaining on the depleted diet. The most prominent expression increases
      were observed with Ptger2 (a prostaglandin E receptor), Tcrb-V13 (a T-cell
      receptor beta), Tcf-7 (a T-cell transcription factor), and Lck (lymphocyte
      protein tyrosine kinase), and the major consistent decrease was Vav2, an oncogene
      in mice consuming the selenium containing diets.

PMID- 16444007
TI  - Influence of lanthanum on the accumulation of trace elements in chloroplasts of
      cucumber seedling leaves.
AB  - Influence of La3+ on the accumulation of trace elements (75Se, 56 Co, 83 Rb, 48
      V, 95 mTc, and 67Ga) in chloroplasts of cucumber seedling leaves was studied by a
      radioactive multi-tracer technique. At the same time, chloroplast contents of
      different concentrations of La3+ treatment were calculated. It was observed that
      chloroplast contents peaked at 0.02 mM La3+ treatment and that the uptake and
      distribution of these trace elements in chloroplasts of cucumber seedling leaves
      are different under different La3+ treatments. With the increase of lanthanum
      concentrations from 0.002 to 2 mM, the uptake percentages of 75Se, 56 Co, and 83
      Rb presented an obvious increase and then sharply decreased in contrast to the
      non-lanthanum treatment, whereas there appeared a sharp decrease and then
      restored control level in the uptake of 48 V. The other two trace elements,
      namely 95 mTc and 67Ga, were accumulated only in the presence of 0.02 mM La3+.
      The results indicate that lanthanum treatments to growing the cucumber lead to
      the change of trace element uptake in the chloroplasts of leaves, which suggest
      that lanthanum might influence the accumulation of trace elements in chloroplasts
      of cucumber seedling leaves by regulation of various ion transport mechanisms,
      thus affecting the photosystem of leaves.

PMID- 16444008
TI  - On the interaction of vanadium species with meso-2,3-dimercaptosuccinic acid.
AB  - The interaction of the VO2+ cation with meso-2,3-dimercaptosuccinic acid (DMSA)
      was investigated by electron absorption spectroscopy in aqueous solution at
      different pH values. The spectral behavior, complemented with a
      spectrophotometric titration, shows the generation of a [VO(DMSA)2]2- complex in
      which the oxocation interacts with two pairs of deprotonated -SH groups of the
      acid. It was also found that DMSA rapidly reduces VO3- to VO2+, which might be
      chelated by an excess of the acid. DMSA can also produce the partial reduction of
      a V2O5 suspension at pH=5.2. The results of this study suggest that DMSA might be
      a potentially useful detoxification agent for vanadium.

PMID- 16444009
TI  - Iron bioavailability from fortified petit suisse cheese determined by the
      prophylactic-preventive method.
AB  - In this research, we measured the iron bioavailability of ferrous gluconate
      stabilized with glycine (SFG) when it is used to fortify petit suisse cheese
      using the prophylactic-preventive method in rats. Three groups of male, weaned
      rats received a basal diet (control diet; 5.2 ppm Fe), a reference standard diet
      (SO4Fe; 9.2 ppm Fe), and a basal diet using iron-fortified petit suisse cheese as
      the iron source (cheese diet; 8.8 ppm Fe) for 22 d. The iron bioavailability was
      calculated as the ratio between the mass of iron incorporated into hemoglobin and
      the total iron intake per animal during the treatment. These values (BioFe) were
      68% and 72% for SFG and ferrous sulfate, respectively. The value of the Relative
      Biological Value (RBV) was 95% for SFG in petit suisse cheese. These results show
      that according to this method, the iron bioavailability from industrial fortified
      petit suisse cheese can be considered as a high bioavailability rate.

PMID- 16444010
TI  - Expression of a synthetic cholera toxin B subunit in tobacco using ubiquitin
      promoter and bar gene as a selectable marker.
AB  - A protocol has been developed to produce a cholera toxin B subunit (CTB) in
      tobacco tolerant to the herbicide phosphinothricin (PPT) by means of in vitro
      selection. The synthetic CTB subunit gene was altered to modify the codon usage
      to that of tobacco plant genes. The gene was then cloned into a plant expression
      vector and was under the control of the ubiquitin promoter and transformed into
      tobacco plants by Agrobacterium-mediated transformation. Transgenic plantlets
      were selected in a medium supplemented with 5 mg/L PPT. Polymerase chain reaction
      analysis confirmed stable integration of the synthetic CTB gene into a
      chromosomal DNA. A high level of CTB (1.8% of total soluble protein) was
      expressed in transgenic plants, which was 18-fold higher than that under the
      control of the expressed CaMV 35S promoter with native gene. The transgenic
      plants when transferred to a greenhouse proved to be resistant to 2% PPT.

PMID- 16444011
TI  - Fluorogenic LUX primer for quantitation of HIV-1 by real-time RT-PCR.
AB  - Measurement of HIV-1 viral load in plasma is an important marker of disease
      progression and efficacy of antiretroviral therapy. Real-time polymerase chain
      reaction (PCR) offers an opportunity to develop more affordable alternative viral
      load assays. This article reports on the development of a novel real-time reverse
      transcriptase (RT)-PCR assay for quantitation of HIV-1 RNA copies. This assay
      utilizes the LightCycler (version 2) real-time PCR platform and light upon
      extension (LUX) primer for specific detection of amplicons. An external standard
      (ES) for quantitation of viral RNA represents an in vitro transcribed RNA. The
      LUX assay shows a wide linear (R2 = 0.99) dynamic range from 4 x 10(6) to 4 x
      10(2) copies/mL. Analytical sensitivity of the assay is 4 x 10(2) copies/mL of ES
      RNA. Intra- and inter-assay variability of the LUX assay was less than 0.5log(10)
      copies of ES RNA (i.e., no clinically significant variability was found).
      Virology quality assurance (VQA) HIV-1 RNA copy controls were used to validate ES
      and preliminarily evaluate the assay performance. This feasibility study
      demonstrated that the LUX assay is sensitive, reproducible, and compares well to
      the Roche Amplicor tests used for characterization of the RNA copy controls.
      These results suggest further evaluation of the LUX assay using a large cohort of
      well-characterized samples from HIV-1 positive individuals.

PMID- 16444012
TI  - Evaluation of PCR-based methods for isolating flanking regions of genes.
AB  - Several polymerase chain reaction (PCR)-based methods are available for isolation
      of unknown genomic fragments. In the present study, a comparative evaluation of a
      few methods of ligation-mediated PCR methods and a ligation-independent one were
      made by isolating promoter fragment for N-methyltransferase gene involved in the
      caffeine biosynthetic pathway of Coffea canephora. The benefits of tertiary PCR
      and the effects of a 4-base cutting restriction endonuclease on the size of the
      PCR products obtained were demonstrated in one of the ligation-mediated PCR
      methods. The methods adopted in this study differed in the sizes of the 5'
      flanking regions obtained. The efficiencies of various methods used reflect the
      inherent limitations of the PCR-based methods for isolation of unknown flanking
      regions.

PMID- 16444014
TI  - Evaluation of agrobacterium-mediated transformation of Agaricus bisporus using a
      range of promoters linked to hygromycin resistance.
AB  - There is interest in establishing genetic modification technologies for the
      cultivated mushroom Agaricus bisporus, both for improved crop characteristics and
      for molecular pharming. For these methods to be successful, it is necessary to
      establish a set of transformation systems that include robust and reliable
      vectors for gene manipulation. In this article, we report the evaluation of a
      series of promoters for driving expression of the Escherichia coli hph gene
      encoding hygromycin phosphotransferase. This was achieved using the Aspergillus
      nidulans gpdA and the A. bisporus gpdII and trp2 promoters. The Coprinus cinereus
      beta-tubulin promoter gave contrasting results depending on the size of promoter
      used, with a 393-bp region being effective, whereas the longer 453-bp fragment
      failed to yield any hygromycin-resistant transformants. The C. cinereus trp1 and
      the A. bisporus lcc1 promoters both failed to yield transformants. We also show
      that transformation efficiency may be improved by careful selection of both
      appropriate Agrobacterium strains, with AGL-1 yielding more than LBA1126 and by
      the choice of the binary vectors used to mobilize the DNA, with pCAMBIA vectors
      appearing to be more efficient than either pBIN19- or pGREEN-based systems.

PMID- 16444013
TI  - Synthesis of a ricin toxin B subunit-rotavirus VP7 fusion protein in potato.
AB  - A gene encoding the outer capsid glycoprotein (VP7) of simian rotavirus SA11, was
      genetically linked to the amino terminus of the ricin toxin B subunit (RTB)
      isolated from castor-oil plant (Ricinus communis) seeds. To assess fusion protein
      expression in plant cells, the VP7::RTB fusion gene was transferred into potato
      (Solanum tuberosum) cells by Agrobacterium tumefaciens-mediated transformation
      methods and transformed plants regenerated. The fusion gene was detected in
      transformed potato genomic DNA by polymerase chain reaction DNA amplification
      methods. Immunoblot analysis with anti-SA11 antiserum as the primary antibody
      verified the presence of VP7::RTB fusion protein in transformed potato tuber
      tissues. The plant-synthesized fusion protein bound RTB membrane receptors as
      measured by asialofetuin-enzyme-linked immunosorbent assay (ELISA). The ELISA
      results indicated that the VP7::RTB fusion protein was biologically active and
      made up approx 0.03% of total soluble transformed tuber protein. The biosynthesis
      of receptor binding VP7::RTB fusion protein in potato tissues demonstrates the
      feasibility of producing monomeric ricin toxin B subunit adjuvant-virus antigen
      fusion proteins in crop plants for enhanced immunity.

PMID- 16444015
TI  - Nickel resistance in fission yeast associated with the magnesium transport
      system.
AB  - We isolated and characterized a nickel (Ni2+)-resistant mutant (GA1) of
      Schizosaccharomyces pombe. This mutant strain displayed resistance to both Ni2+
      and Zn2+, but not to Cd2+, Co2+, and Cu2+. The growth rate of GA1 increased
      proportionally with increasing Mg2+ concentrations until 50 mM Mg2+. The GA1
      mutation phenotype suggests a defect in Mg2+ uptake. Sequence analysis of the GA1
      open reading frame (ORF) O13779, which is homologous to the prokaryotic and
      eukaryotic CorA Mg2+ transport systems, revealed a point mutation at codon 153
      (ccc to acc) resulting in a Pro153Thr substitution in the N-terminus of the CorA
      domain. Our results provide novel genetic information about Ni2+ resistance in
      fission yeast. Specifically, that reducing Mg2+ influx through the CorA Mg2+
      transport membrane protein confers Ni2+ resistance in S. pombe. We also report
      that Ni2+ ion detoxification of the fission yeast is related to histidine
      metabolism and pH.

PMID- 16444018
TI  - [Estimation of efficiency of complex-method intestinal therapy using Nitella
      flexilis test-object for acute intestinal obstruction of various etiology].
AB  - The aim of our investigation was to define the presence of correlation between
      toxicity of intestinal contents and clinical and laboratory indices in the cases
      of ileus and peritonitis with the use of complex method of enteral therapy.
      Experiments have been carried out on internodal cells of Nitella Flexilis water
      plant. Efficiency of the given method (investigation of toxicity of the
      intestinal content with the use of test-object Nitella Flexilis) has been studied
      in 25 patients, who underwent correction of morpho-functional status of small
      intestine. Results of investigation have shown that changes in toxicity of
      intestinal content reliably reflect the nature and dynamics of the pathobiologic
      processes proceeding in GIS in treated patients suffering from acute intestinal
      impassability. Using the method of correction of morpho-functional status of
      small intestine decreases the role of "Intestinal factor" in formation of
      endogenous intoxication, which in turn results in early normalization of clinical
      and laboratory indices, favored process of early post-operational period,
      decreased rate of lethality and shortened rehabilitation period.

PMID- 16444019
TI  - [Application of air-plasma flow for the correction of microcirculation disorders
      during the treatment of diabetic foot syndrome].
AB  - Analysis of data on the treatment of 100 patients with purulent-necrotic forms of
      diabetic foot syndrome is presented. Patients were divided into two groups. In
      the first group (45 patients) treatment was conducted using traditional methods
      and techniques. In the second group (55 patients) during operation air-plasma
      cutting-coagulation device "Plazon" was used in NO-therapy mode. Nitric monoxide
      is known as multifunctional antioxidant substance, having great value in
      oxidative stress reactions. In the current study it was transported to the wound
      surface by air-flow of "Plazon" device. The condition of microcirculation in
      tissues was studied by computerized laser capillary flow analyzer "LAKK-01". It
      was shown that after removing inflammation in the healed wound, condition
      corresponding to characteristics of undamaged skin takes place in contrast to the
      patients from the group 1, where some asymmetry in the foot tissues
      microcirculation was shown as an evidence of functional and structural
      insufficiency of microcirculation system.

PMID- 16444016
TI  - Mouse models of triplet repeat diseases.
AB  - Triplet repeat expansions were first discovered in 1991 and since then have been
      found to be the mutation underlying a range of neurodegenerative, neuromuscular,
      and cognitive disorders including fragile X syndrome, myotonic dystrophy,
      Friedreich's ataxia, and the polyglutamine disorders that include Huntington's
      disease. The repeats exert their detrimental effects through different molecular
      mechanisms dependent on whether they are located in coding or noncoding regions
      of the gene in question. During the past 10 yr, a wide range of strategies have
      been used to successfully establish mouse models for all of these disorders. This
      review presents an overview of these mouse models, discusses the insights into
      the molecular pathogenesis of these disorders that have been gained from their
      analysis and the strategies that are being used to uncover novel therapeutic
      options.

PMID- 16444020
TI  - [Minimally invasive surgery for the treatment of pancreatic fistulas].
AB  - Results of treatment of 6 patients with pancreatic fistula by US-, radioscopy-,
      and endoscopy-guided formation of transcutaneous pancreatogastric anastomosis are
      presented. The procedure of pancreatogastric anastomosis is described. The causes
      of formation of fistulas were: operations due to pancreatitis - 4 cases, trauma
      of a pancreas -- 1 case, percutaneous drainage of a cyst -- 1 case. By
      application of the given procedure, complete closure of a fistula without
      relapses (maximal term of observation 1 year) was possible. The complications
      linked to performance of transcutaneous manipulation have not been noted.
      Lethality was not observed. It may be assumed, that the developed original
      procedure and using the Ivshin's device for the drainage of cavity formations can
      become a method of a choice in the treatment of patients with non-perishable
      outside pancreatic fistulas. Assessment of the parameters of the quality of life
      has shown that patients were quickly reverted to social and intellectual
      activity.

PMID- 16444017
TI  - Chiral separation principles in chromatographic and electromigration techniques.
AB  - Almost half of the drugs in use today are chiral. It is well established that the
      pharmacological activity is mostly restricted to one of the enantiomers
      (eutomer). There can be qualitative and quantitative differences in the activity
      of the enantiomers. In many cases, the inactive enantiomer (distomer) shows
      unwanted side effects or even toxic effects. Even if the side effects are not
      that drastic, the distomer has to be metabolized and this represents an
      unnecessary burden for the organism. Therefore, the development of methods for
      the separation of enantiomers, both on analytical and preparative scale, has
      become increasingly important. Chromatographic techniques such as thin layer
      chromatography (TLC), gas chromatography (GC), supercritical fluid chromatography
      (SFC), and above all high-performance liquid chromatography (HPLC) have been used
      for enantiomer separation for about two decades. More recently, electromigration
      techniques, such as capillary electrophoresis and capillary
      electrochromatography, have been shown to be powerful alternatives to
      chromatographic methods. This review gives a short overview of different chiral
      separation principles and their application. Several new developments are
      discussed.

PMID- 16444021
TI  - [Strategy of treatment of patients with colorectal cancer with hepatic
      metastases].
AB  - Retrospective study was performed to evaluate the efficacy of combined methods of
      treatment in patients with colorectal cancer with hepatic metastases. 57 patients
      (I group - control) undergone regional chemotherapy (RC) with hepatic arterial or
      intraportal 5Fluorouracil (5FU). From 84 patients 48 (II group) undergone liver
      resection + RC (5FU), 24 (III group) - hepatic arterial embolization +RC (5FU),
      and 12(IV group) with multiple bilobar (<3 cm) metastases- alcoholization of
      metastatic nodules +RC (5FU). Overall 5-year survival for the II group was 14.8%
      without operative or postoperative deaths. The median survival was 19 months
      (range 13-27 months) and 21 months (range 15-26 months) for II and III groups
      respectively, which is not different from the survival rate of patients who
      received only RC. Although, quality of life was much better after combined
      treatment. Resection of colorectal liver metastases followed by regional
      chemotherapy can provide long-term survival in selected patients.

PMID- 16444022
TI  - [The frequency and character of clinical manifestations of androgenization among
      adolescent girls].
AB  - By clinical examination of 700 adolescent girls aged 11-17 high frequency of
      androgen depended manifestations, such as acne, seborrhea, hypertrichosis or
      their combination was detected in prepubertal and pubertal periods (4.7%, 6.8%,
      2.9% and 20.6%, 5.3%, 3.0% correspondingly). Above-mentioned signs developed as a
      result of activation of androgens secretion by adrenal glands and ovaries, which
      are physiological processes during pubertal period. The combination of these
      signs with hirsutism and menstrual disorders may be a manifestation of endocrine-
      reproductive disorders. Results of our data indicate to infirmity, expediency and
      importance of prophylactic examination among adolescent girls. Low rate of
      attendance to medical care among adolescents with clinical manifestations with
      probable endocrine and reproductive disorders indicates to the importance of
      their early diagnosis during adolescence and timely initiation of the treatment.

PMID- 16444023
TI  - Proliferation and apoptosis in ovarian stromal hyperplasia and hyperthecosis.
AB  - The aim of our study was to investigate proliferation and apoptosis in ovarian
      stromal hyperplasia and hyperthecosis in reproductive women with and without
      polycystic ovarian disease. We have studied 104 patients with a histological
      diagnosis of ovarian stromal hyperthecosis and stromal hyperplasia. Paraffin
      sections were stained by hematoxylin-eosin, von Gieson and immunohistochemistry
      for Bcl-2 (anti-apoptotic protein) and Ki-67 antigen (proliferation marker). We
      assessed the number of Bcl-2-positive and Ki-67-positive cells. The patients were
      divided into 4 groups: group 1 -- 33 patients with polycystic ovarian disease and
      coexistent stromal hyperthecosis, group 2 -- 28 patients with polycystic ovarian
      disease and coexistent stromal hyperplasia, group 3 -- 24 patients with ovarian
      stromal hyperthecosis, group 4-19 patients with ovarian stromal hyperplasia. The
      results suggest that in ovarian stromal hyperthecosis coexistent with polycystic
      ovarian disease luteinized stromal cells show high proliferation activity and
      resistance to apoptosis, and internal and external theca cells show resistance to
      apoptosis. In ovarian stromal hyperplasia coexistent with polycystic ovarian
      disease, hyperplastic stromal cells show high proliferation activity and
      resistance to apoptosis. Proliferation activity is also increased in vascular
      endothelial and smooth muscle cells. Internal and external theca cells show
      resistance to apoptosis. In ovarian stromal hyperthecosis without polycystic
      ovarian disease, luteinized stromal cells show high proliferation activity and
      resistance to apoptosis. In ovarian stromal hyperplasia without polycystic
      ovarian disease, hyperplastic stromal cells show high proliferation activity and
      potential susceptibility to apoptosis. Proliferation activity is also increased
      in vascular endothelial and smooth muscle cells. These characteristics of
      proliferation and apoptosis have meaning in pathogenesis of ovarian stromal
      hyperthecosis and stromal hyperplasia with and without polycystic ovarian
      disease.

PMID- 16444024
TI  - [Intrauterine growth retardation in preterm labor and delivery].
AB  - We have done retrospective analysis of pregnancy, labor, delivery and neonatal
      period in 155 women with preterm labor. 78 of them delivered infants with
      intrauterine growth retardation (IUGR) and 77 women delivered immature infants
      compared to gestational age. Morphological changes are most prominent in fetal
      part of placenta, which disturbs blood flow to mother-fetus-placental unit, which
      in turn leads to intrauterine growth retardation and poor neonatal outcome -- in
      78% of cases hypoxic-ischemic CNS disease, in 53% of cases occurs respiratory
      distress syndrome, pathological functional state and immature cerebral structures
      according to EEG. Based on case-control study it was documented, that preterm
      birth is one of the risk factors of IUGR, Odds Ratio is equal to 1.22. Preterm
      birth of any origin occurs in association with placental insufficiency.

PMID- 16444025
TI  - Prevalence and risk factors for Chlamydia trachomatis infection in pregnant
      women.
AB  - The aim of this study was to determine the prevalence and risk factors for
      Chlamydia trachomatis infection in pregnant women. A total of 351 asymptomatic
      pregnant women (first to second trimesters; age range: 15-30 years) were
      examined. The background data related to social and marital status, age,
      anamnestic data were also recorded. Serum samples were tested for IgM antibodies
      specific to Chlamydia trachomatis by an enzyme-linked immunosorbent assay
      (ELISA). In the present study the overall rate of C trachomatis infections in
      pregnant women was 33% including 41 women (38.7%) under 20 years, 39 women
      (36.8%) in age of 21-25, and 26 women (24.5%) in age of 25-30. The age group
      under 20 years exhibited higher risk of infection. There was a significant
      correlation between the Chlamydia trachomatis infection rate and clinical risk
      factors such as rare visits to the gynecologist, pelvic inflammatory disease,
      premature delivery, spontaneous abortions, ectopic pregnancies, C. trachomatis
      positivity, chlamydial cervicitis in anamnesis. The prevalence of asymptomatic C.
      trachomatis infection in pregnant women is 72.6%, therefore, we suggest the
      screening for chlamydial infection of all pregnant women at least once during
      their pregnancy.

PMID- 16444026
TI  - [Characteristics of occlusal plane in patients with class iii malocclusion].
AB  - Occlusive plane of teeth is the line of teeth which connects upper and lower
      teeth. Direction and level of occlusive plane determines normal function of dento
      skeletal system and is very important for facial aesthetics. The aim of our study
      was to determine position of occlusive plane in relation to alveolar bases of
      upper and lower jaws in patients with class III malocclusion, also to analyze
      characteristics of occlusive plane changes during the growth. After analysis of
      the results of our study, we can conclude that during the growth and development
      of facial skeleton occlusive plane of examined patients with class III
      malocclusion rotates counter-clockwise, due to decrease of vertical dimension
      (height) of dento-alveolar segment in lower molar area.

PMID- 16444027
TI  - [Qualitative and quantitative aspects of risk-factors of dentofacial system
      anomalies in children with postural disorders and scoliosis].
AB  - The purpose of the study was to investigate qualitative and quantitative aspects
      of risk-factors of dentofacial system anomalies in children with postural
      disorders and scoliosis. We have examined 600 children at the age of 6-15 with
      postural disorders and scoliosis (study group), also 100 children without
      postural disorders and scoliosis (control group) and 100 practically healthy
      children (children without postural disorders, scoliosis and dentofacial
      anomalies). The spread of dentofacial anomalies in children of the study group
      was 70.2%, in the control group -- 41.0%. For the estimation of the degree of
      association between the disease frequency and certain risk-factors, chi(2)
      indicator has been calculated. In the examined population simultaneous existence
      of several factors prevailed. High frequency of the combination of risk factors
      (simultaneous existence of 5-7 factors in average) was found, which was much more
      frequent (p<0.001) in the contingent of the study and the control groups (3-4
      times) than in the group of practically healthy children.

PMID- 16444029
TI  - [Role of morpho-functional changes of blood lymphocytes in pathogenesis of
      psoriasis and the possibilities for their correction].
AB  - It is well known, that the cells of T-lymphoid population including Th2
      lymphocytes of the skin, as well as circulating cells has the great importance in
      the pathogenesis of psoriasis. The goal of given research was to define the role
      of morpho-functional changes in blood lymphocytes in the pathogenesis of
      psoriasis and the possibilities for their correction. On the background of our
      investigation it could be concluded that in the case of the vulgar form of
      psoriasis in peripheral blood lymphocytes the intensified expression of p-53
      preapoptotic protein results from affecting of NO induced damage of DNA molecule,
      in terms of intensification of oxidative stress in organism, which contributes to
      the activation of apoptosis of peripheral blood lymphocytes and is presented as
      one of the reasons which can cause the degradation of lymphocyte-induced
      apoptosis of keratinocytes. After the course of balneal therapy in "Nunisi" the
      decrease in expression of p-53 lymphocytes has been observed, big lymphocytes are
      predominant ones, with indications of synthetic activity of ultrastructure. This
      effect is conditioned by antioxidative characteristics of waters of "Nunisi"
      which assists to decreasing of the oxidative stress in patient's organism and
      recovers redox state of nitrogen oxide; it contributes to the intensification of
      keratinocytes apoptosis and to the prompt clearance of psoriatic lesion foci in
      epidermis.

PMID- 16444028
TI  - [Dynamics of leukocytes' migration degree in oral cavity and parameters of
      INFgamma and TNFalpha in blood serum of patients suffering from parodontitis on
      the background of treatment with Unimag].
AB  - In the oral cavity of patients with parodontitis before treatment the quantity of
      migrated leukocytes (ML) was increased. Among them number of living cells was
      sharply reduced. In the process of treatment on the background of immune
      modulation with Unimag, the concentration of migrated leukocytes decreases and
      number of living leukocytes increases. The above-mentioned quantitative and
      qualitative parameters of migrated leukocytes were normalized after 1-1.5 months.
      The analogical dynamics has been detected in patients suffering from parodontitis
      and treated with traditional scheme. However, despite reduced concentration of
      migrated leukocytes and increased percentage of living leukocytes' content,
      normalization of the mentioned parameters has not been detected. In the blood
      serum of patients suffering from parodontitis increased concentration of INFgamma
      and TNFalpha have been revealed. In the process of treatment, concentration of
      the mentioned cytokines was decreased, however, in patients treated with Unimag
      on the background of immune modulation, decrease in concentration of INFgamma and
      TNFalpha was much more expressed.

PMID- 16444030
TI  - [Dermatosis in children with diabetes mellitus].
AB  - Many endocrine diseases are accompanied by skin damage. It is induced by initial
      hormonal and metabolic disorders, manifestates at the early stage of the disease
      and represents very important diagnostic sign. Clinical peculiarities of diabetes
      mellitus dermal manifestations in children are presented in this review paper.
      Number of dermatosis are discussed which are mainly due to the disturbances of
      carbohydrate metabolism (skin itching, pioderma, candidosis, xanthochromia,
      eczema, psoriasis, necrobiosis lipoidica, granuloma annulare, xanthomatosis,
      black acanthosis, porphyria). Author suggests that during examination of children
      with different type of dermal pathology, dermatologist must suspect existence of
      diabetes mellitus and should investigate such cases for the presence of this
      disease. In other words, dermatologist can contribute in the early revelation of
      diabetes mellitus in children.

PMID- 16444031
TI  - [Effect of prestarium in patients with chronic heart failure].
AB  - The main active factor in the progression of chronic heart failure (CHF) is a
      renin-angiotensin system (RAS), namely its main hormone angiotensin-II, which
      induces variety effects of given neurohormonal system (vasoconstriction,
      increased arterial pressure, hypertrophy, and fibrosis). It diminishes the role
      of the etiological factor and determines the quality to life and prognosis of the
      disease. Prestarium as an angiotensin-converting enzyme inhibitor significantly
      improved the functional class (FC) and increased the 6 min distance of walking.
      In addition, patients reported a slight improvement of life quality. Prestarium
      consistently improved all major parameters of central hemodynamics, with a
      statistically significant improvement of end systolic volume and LV ejection
      fraction by 3 months. Therefore Prestarium improved the clinical status and
      exerted beneficial effects on LV volumes and LV contractile capability in
      patients with CHF.

PMID- 16444033
TI  - [Clinical and hemodynamic efficiency of dilatrend treatment in patients with
      dilatation cardiomyopathy].
AB  - In present study we describe the clinical case of successful treatment of
      dilatation cardiomyophaty based on dilatrend using. 32 years old patient with
      acute heart failure and rhythm dysfunction was active user of alcohol since 1993.
      At the beginning of treatment 25 mg of dilatrend twice per day was used. The dose
      was increased monthly by 2.5 mg. After 4 months of treatment clinical signs of
      disease were eliminated at the daily dose 50 mg of dilatrend. In order to recover
      from arrhythmia on the seventh month of treatment cardioversion was successfully
      carried out. As it follows from our experience dilatrend is very effective for
      treatment of dilatative cardiomyopathy of alcoholic genesis.

PMID- 16444032
TI  - Lipoprotein profile and endothelial function in patients with subclinical and
      overt hypothyroidism.
AB  - The aim of the present study was to evaluate the lipoprotein profile and
      endothelial function in patients with overt hypothyroidism, SCH and euthyroid
      subjects and to assess the effects of these conditions on endothelial function.
      The TOSHIBA SSH-140-A unit was used to measure brachial artery (BA) diameter and
      blood flow velocity at rest and after occlusion by high pressure cuff. To induce
      FMD we used EDRF release test. BA was occluded by high pressure cuff for 2
      minutes with pressure 50 mmHg higher then systolic blood pressure. 23 SCH (I
      group) women were recruited for study. We compared them with 21 patients with
      overt hypothyroidism (II group). The III group contained 26 euthyroidal women.
      The results of examination have shown that overt hypothyroid patients have
      significantly higher TC, LDLc and TG levels than controls, positively correlated
      with TSH and inversely correlated with FT4 levels. SCH patients have less marked
      changes, but significant positive relationships were found between serum TSH and
      TC and LDLc. It is important as a risk factor for cardiovascular disease. Flow
      mediated, endothelium-dependent vasodilatation was significantly higher in
      control group (10.7+/-0.8%) compared with subjects SHT (6.5+/-0.5%) and patients
      with overt hypothyroidism (5.2+/-0.4%). TSH levels correlated inversely to
      endothelium-dependent dilatation. Thus, FMD, a marker of endothelial function, is
      impaired not only in patients with overt hypothyroidism, but also in subjects
      with SCH.

PMID- 16444034
TI  - [Clinical-epidemiological study of patients with toxic liver diseases].
AB  - To evaluate effects of potentially hepatotoxic factors on the body we have
      studied medical histories of 3382 patients hospitalized at the
      toxicoresuscitation unit of the TSU Clinical Hospital and at the University
      Therapy Clinic of the City Hospital N1 during 2000-2004. It was found out that
      the most common etiologic causes of intoxication are medicines and alcohol. The
      role of chemical substances is also significant. The number of effect of other
      etiologic factors is lower. Intoxications due to potentially hepatotoxic agents
      by years were observed in 68.25%; 68.18%; 80.35%; 75.31%; 64.42% of cases of
      accidental drug-induced intoxication and in 55.00%; 59.32%; 52.03%; 53.33%;
      69.09% of drug-induced suicidal cases and these drugs represented various
      pharmacologic groups. Intoxication with combined drugs occurs mainly in cases of
      suicide. Effect of organic and non-organic substances in accidental intoxications
      and suicidal cases are similar. According to the data of the National Center for
      Diseases Control the number of patients with toxic liver injury during 2000 to
      2004 yy. accounts for 0.42%, 014%, 0.06%, 0.89%, 1.17% of patients discharged
      from Tbilisi hospitals with diagnosis of chronic liver disease and 0.81%; 1.12%;
      1.19%; 1.07%; 1.23% of patients being under the supervision of outpatient clinics
      at the end of the year respectively, this does not reflect actual state based on
      the observed effects of potentially hepatotoxic medicines and chemical substances
      and requires from clinicians to pay more attention to this problem.

PMID- 16444035
TI  - Physical rehabilitation of stroke patients and redox alterations.
AB  - We studied 43 acute stroke patients: 22 patients were randomly assigned to the
      experimental group and 21 patients - to the control group. Experimental group
      patients underwent neuro-muscular electric stimulation (NMES) in addition to
      standard rehabilitation regimen. Pro- and antioxidant activity was evaluated at
      admission and at the end of acute stage: paramagnetic centers of blood
      (ceruloplasmin, Fe(3+) transferrin, Mn(2+), Fe(2+), MetHb, NO, HbNO, FeSNO) were
      investigated by EPR-spectroscopy. We observed excessive formation of promoters of
      free-radical oxidation and inactivation of antioxidative protection system.
      Concentration of free NO was decreased in majority of the patients. Following
      NMES application, we observed normalization of almost every parameter of redox
      system: inactivation of Fe(3+) and Mn(2+) ions, increase of total concentration
      of ceruloplasmin and decrease of its oxidation degree, increase of Fe(3+)
      transferrin level, decrease of MetHb concentration, normalization of free NO.
      These alterations were more prominent compared to the control group patient
      (p<0,05). We conclude, that NMES facilitates restoration of the balance between
      pro- and antioxidative systems and decreases intensity of oxidative stress.

PMID- 16444037
TI  - [Modern management of attention-deficit and hyperactivity syndrome (ADHD) in
      preschool children].
AB  - The aim of the study was to detect the ADHD syndrome in preschool children and
      elaboration of therapeutic recommendations. We have examined 84 patients with
      ADHD syndrome. Their age varies from 6 to 10 years. The first group of patients
      had the history of hypoxic-ischemic encephalopathy, while the second group had no
      perinatal pathology. Common level of intellectual development in the both groups
      of children was normal, which gave them ability to attend usual secondary school
      (IQ approximately equals 85-92). Physical data were normal as well. ADHD syndrome
      was revealed in the both groups of patients. Symptoms discovered in the II group
      of patients indicated to the preexistence of perinatal pathology, which was not
      noticed in the medical record. The incidence and expression of symptoms were more
      prominent in the I group of patients.

PMID- 16444036
TI  - [INF-gamma during respiratory-syncytial induced obstructive respiratory syndrome
      in infection in children under one year of age].
AB  - Lately the connection of Asthma and RSV drew the sufficient attention. The
      recurrent wheezing developed during the RSV in children is particularly frequent
      in the families having history of atopy. The decreased expression of INFgamma may
      play the role in the pathogenesis of RSV infection. The target of our research
      was the study of the rate of INFgamma during various clinical courses of RSV
      infection and definition of its role in the pathogenesis of ARVI. 52 children
      with RSV-associated wheezing have been studied, who had first (32) or recurrent
      episode (20) of bronchial obstruction and whose families had occurrence of atopy.
      52 children with non RSV-associated wheezing (III group) and 10 healthy children
      up to 12 months of age (IV group) were considered as the control groups. Children
      from all four groups were from families with the history of atopy. INFgamma was
      measured by enzyme immunoassay (ELISA). Comparison of two groups of wheezing
      children with RSV infection showed significant reduction of INFgamma level in the
      group of children with recurrent wheezing vs. the group with first episode of
      wheezing. INFgamma levels were significantly higher in the two control groups.
      During the acute respiratory infection induced by RS-virus, which proceeds with
      the obstruction of respiratory tract (wheezing), reduction of INFgamma was noted
      and higher frequency of wheezing episodes is associated with more prominent
      alteration.

PMID- 16444038
TI  - Procalcitonin as the biomarker of inflammation in diagnostics of pediatric
      appendicular peritonitis and for the prognosis of early postoperative
      complications.
AB  - A total of 43 patients up to 15 years, who underwent appendectomy with
      preliminary diagnosis of acute appendicitis have been studied at M. Guramishvili
      Pediatric Clinic in 2004-2005 years. Procalcitonin concentration has been defined
      in patients' blood sera using the immunoluminometric method (LUMITest PCT, BRAHMS
      Diagnostika, Berlin, Germany). Analysis of procalcitonin in different groups of
      patients has shown that increase in procalcitonin correlates with disease
      severity, and maximally increases in case of peritonitis due to acute destructive
      appendicitis. The procalcitonin level can be used to confirm the diagnosis of
      acute appendicitis. It has been suggested that procalcitonin can be used not only
      as diagnostic marker for acute appendicitis but also as a prognostic marker of
      it's complications. Using of procalcitonin in case of acute appendicitis would
      help to carry out timely surgical interventions and predict disease
      complications.

PMID- 16444039
TI  - [Early predictors of neurodevelopmental outcome of neonatal bacterial
      meningitis].
AB  - 154 patients, who were hospitalized in M. Iashvili Children's central hospital in
      1998-2005 were investigated. In 70 cases the diagnosis was neonatal bacterial
      meningitis, in 62 cases -- bacterial sepsis and neonatal meningitis and 22 cases
      patients were in control group with the diagnosis of neonatal bacterial sepsis.
      From base investigation group -132 patients were divided in two group, in which
      patients were united by the starting point of disease from the birth: first group
      included newborns with signs of disease on earlier stage (sings of the disease
      showed up during 24-72 hours from the birth); second group included newborns with
      later signs of disease (after 72 hours from the birth). Our conclusion is-
      outcome of bacterial meningitis depends on the starting point of disease.
      Meningitis which began earlier than 72 hours of life, characterized by severe
      prognosis. Mother's chronic infection diseases and brain injury of newborn are
      predictors of severe complications of neonatal bacterial meningitis. Such
      complications of bacterial meningitis as are: brain abscess, ventriculitis,
      neonatal seizures, coma and neutropenia, become predictors of severe latest
      outcome.

PMID- 16444041
TI  - Importance of correlations of gross motoric functions data and functional
      independence for management of children with motoric disabilities.
AB  - The aim of the rehabilitation therapy is to improve the level of functional
      independence and decrease degree of disability. The optimization of programs of
      rehabilitation means functional improvement of the person, and this approach is a
      basis of effective management. To evaluate the correlation of Gross Motoric
      Function Data and Functional Independence Measure for children with cerebral
      palsy. A total of 397 children with cerebral palsy aged 1 to 12 years at the
      onset of study were observed for up to 3.5 years during the period from 2002 to
      2005. Children were assessed by GMFM-88 (Gross Motor Function Measure), by WeeFIM
      (Functional Independence Measure for Children). Over the course of the study 397
      children had a total of 6875 GMFM assessments, or an average of 17.3 observations
      per child and 1518 -- WeeFIM, or an average of 3.8 observations per child. The
      values of GMFM-88 and WeeFIM are well correlated (p<0.01). At certain stage of
      rehabilitation treatment the rate of improvement of gross motoric function slows
      down and then practically stops. In patients with gross motoric function level IV
      V its value remains especially low, and accordingly there is no improvement of
      functional abilities. This is the main reason of ineffectiveness of
      rehabilitation treatment and necessity of tertiary care preventive measures.

PMID- 16444040
TI  - [Visceral leishmaniasis: clinical and epidemiological features among children and
      adolescents in Georgia].
AB  - The aim of the study was to describe the clinical and epidemiological features of
      children and adolescents with visceral leishmaniasis in Georgia. We performed a
      retrospective analysis of demographic, clinical and laboratory data from children
      and adolescents under age of 18 (n=200) with visceral leishmaniasis admitted to
      the referral center -- Tbilisi S. Virsaladze Institute of Parasitology between
      2000 and 2005. Diagnosis was based on detection of amastigotes in the bone marrow
      punctate. Age ranged from 4 months to 15.9 years, the average age was 2.79+/-0.17
      years. There were 84 girls and 116 boys. 190 cases came from Eastern Georgia (123
      from the capital), 10 cases -- from Western Georgia. The period between
      manifestation of first clinical signs of the disease and admission to the
      referral center varied from 1 week to 1 year (6.8+/-0,6 weeks in average). Main
      clinical and laboratory presentations were splenomegaly and hepatomagaly, anemia,
      pancytopenia (84.5%). Among associated diseases, the most frequent were
      bronchitis and pneumonia (7.0%) and jaundice (3.5%). In all patients glucantime
      was used for treatment. One patient died. Visceral leishmaniasis can be
      considered as an important etiological agent of the fever of unknown origin in
      Georgia, particularly in Eastern Georgia and in children under six. Health care
      workers should be trained for the early recognition and appropriate management of
      visceral leishmaniasis and its complications.

PMID- 16444042
TI  - Pediatric gastroenterological summer school in Tbilisi, Georgia.

PMID- 16444043
TI  - [Pharmacological correction of hyperactivity of renin-angiotensin-aldosterone
      system].
AB  - Reference data on the function of renin-angiotensin-aldosterone system (RAAS) and
      pharmacological correction of its hyperactivity are summarized and analyzed in
      the paper. RAAS plays important role in the development and worsening of
      hypertension, facilitates proliferation of smooth muscle and heart cells. The
      hyperactivity of RAAS promotes the development of cardiovascular complications,
      such as myocardial infarction, stroke, increases cardiovascular mortality and
      morbidity. Pharmacological correction of RAAS hyperactivity decreases
      hypertension, prevents occlusion of heart and blood vessels, provides anti
      ischemic action, vascular and cardiac protection, improves life style, prevents
      cardiovascular mortality, such as fatal stroke, myocardial infarction and sudden
      death. b-blocker inhibitors, angiotensin converting enzyme (ACE) inhibitors,
      angiotensin AT1-receptors blockers are reviewed as first line therapy of
      essential hypertension and congestive heart failure. ACT inhibitors, AT1-
      receptor blockers decrease total cholesterol, LDL, but increase HDL, beta
      blockers decrease HDL. AT1-blockers are alternative drugs for treatment of
      cardiovascular diseases in those cases where ACE inhibitors are contraindicated
      or intolerance exists.

PMID- 16444044
TI  - [Features of regeneration of joint cartilage during osteoarthritis].
AB  - In order to define the features of regeneration of joint cartilage during
      osteoarthritis, morphological study of surgical material, obtained from 50
      patients, has been performed with the help of histological, histochemical and
      morphometric methods. In the joint cartilage, alongside with the alteration,
      there is also the cellular regeneration expressing in the intensive proliferation
      of cartilaginous cells. However, maturing of the regenerated cells proceeds
      defectively and consequently regenerate loses ability to be differentiated in
      hyaline, joint cartilage that specifies the phase of differentiation. Hence, the
      specified process should be qualified as not reparation, but as a pathological
      regeneration. Cartilaginous regenerate is not capable to carry out amortization
      and protective functions of an articulate cartilage and is exposed to secondary
      alteration. The last, in turn, aggravates arthroses changes and causes
      progressing disease.

PMID- 16444045
TI  - [Detection of Chlamydia infection and estimation of immune reactivity in
      sportsmen by blood leukocyte culture method].
AB  - New method of the diagnosis and cultivation of Chlamydia trachomatis using
      peripheral blood leukocyte cultures is worked out and implemented in the clinical
      practice. This method was used for the diagnosis of asymptomatic chlamydial
      infection in sportsmen. Among 48 sportsmen Chlamydia trachomatis was diagnosed in
      28 persons. Morbidity in these sportsmen was significantly higher, than in
      sportsmen without chlamydial infection. Number of macrophage-lymphocyte rosettes
      in leukocyte cultures that reflects immune reactivity of organism was
      significantly low in sportsmen with Chlamydia trachomatis than in the group
      without this infection. Results of our studies showed that leukocyte culture
      method is the most useful and reliable for the detection of latent or
      asymptomatic Chlamydia trachomatis infection. The diagnosis of this infection in
      sportsmen helps to reveal the reason of different clinical symptoms to carry out
      the appropriate regimen of treatment. Microphotographs of Chlamydia trachomatis
      colonies in the blood leukocyte culture and electron microphotographs of
      different stages of chlamydial life cycle in the host cell in vitro are
      presented.

PMID- 16444046
TI  - [Correlations of anthropometric and psychodynamic indexes of accelerant boys and
      girls (georgians) and their comparing with the data of women and men of normal
      physical development].
AB  - Our goal was to determine relations of anthropometric and psychodynamic indexes
      of accelerant women and men (Georgian) and compare them with the data of women
      and men of normal physical development. For this reason we have investigated 100
      accelerants -- 45 girls and 55 boys. On the basis of our study we have shown that
      correlations between subspecies of temperament and anthropometrical signs in
      accelerant women and men are equal or lower among men. From the point of view of
      character form -- these data in women are comparatively high, and correlation of
      intellect and types of mood and anthropometric signs are equal. In comparison
      with the men of normal development, in accelerant men are noticed law
      interconnection between anthropometrical and psychodynamic data except subspecies
      of intellect, which is equal in every case. Connection between the types of mood
      and anthropometric data are moderate (in the limits 0.3-0.4). Men accelerants
      (Georgians) are brachymorphic somatotypes; they are distinguished by phlegmatic
      temperament, introversion, middle logic intellect, conflict -- statistic mood;
      according to the mood they are harmonic-dynamic constitutional types.

PMID- 16444047
TI  - [Plaferon lb as a protector of radioinducible disorder].
AB  - As it is known, p-53-dependent apoptosis is the cause of the radiosensitive
      cells' rapid death during the first ours after gamma-irradiation. It is
      considered, that short time suppression of the function of p-53 may decrease
      injury of normal tissue. The aim of our study was the determination of the
      effectiveness and possible mechanisms of radioprotective features of plaferon LB.
      It was found that plaferon LB provides correction of content and function of
      nitric oxide in hepatocytes during gamma-irradiation and that may be induced by
      its antioxidant capabilities. By the correction of oxidative metabolism plaferon
      LB decreases intensity of postradiation alterations. The restriction of
      intensification of nitric oxide synthesis after irradiation also results in
      decreasing of iNOS expression. Plaferon LB induces reduction of oxidative stress
      in the organism, also provides NO-modulatory activity. Increase of proapoptotic
      activity of p-53 is due to NO-stimulated DNA-dependent protein kinase and p-38
      mitogen activated protein kinase. It may be concluded that during gamma
      irradiation the preliminary influence of plaferon LB provides prevention of
      hyperproduction of nitric oxide and by this way promotes suppression of NO
      inducible activation of p-53-induced apoptosis.

PMID- 16444048
TI  - [Age related changes of physical-chemical parameters of erythrocytes].
AB  - The aim of our study was to investigate age related changes of physical-chemical
      parameters of erythrocytes. It is known that insufficiency of erythrocytes
      antioxidant defence system in newborns is a keystone of peculiarities manifested
      in homeostasis among this group. The excess volume of reactive oxygen determines
      disorders related to the functioning of cation channels that are represented by
      decrease of K(+) ions, moderate hydration of erythrocytes and may cause
      accumulation of intraerythrocyte calcium. Excessive calcium may also cause
      activation of Ca(2+)-dependent erythrocytes' NOS and increase of nitric oxide
      content in newborns' erythrocytes. However, in spite of high NO content, the
      insufficiency of antioxidant system is conductive to intensive formation of
      methaemoglobin in newborns' blood. The other cause of intensive haemolysis of
      erythrocytes in this age group may be also the activation of Ca(2+)-dependent
      mechanism, which contributes to the exposition of phosphatidilserin on the
      surface of the erythrocyte's membrane and elimination of erythrocytes by
      macrophages. The increasing activity of antioxidant enzymes among aged persons
      seems to be a compensatory mechanism against excessively reactive oxygen in old
      age and this process ensures maintenance of intensity of hemolysis within the
      physiological frames.

PMID- 16444049
TI  - Early cardiotoxicity induced by treatment of hematologic malignancies and the
      risk-factors of its manifestation.
AB  - The aim of the study was to determine the incidence of early cardiotoxicity,
      induced by the treatment of Hemoblastosis and its dependence on the summary dose
      of antracyclins and other risk-factors (age, sex, pre-existing cardiac diseases).
      The study revealed that the summary dose of antracyclins is the important risk
      factor of cardiotoxicity development. Cardiotoxicity was evident when applying >
      or =200 mg/m(2) and < or =200 mg/m(2) doses. The age, above 50, and pre-existing
      cardiovascular diseases, play a vital role. The incidence of the above changes
      was significantly higher in female patients than in male ones. Co-existence of
      different risk-factors further complicates the condition; such cases need deeper
      understanding, dynamic monitoring and early correction.

PMID- 16444050
TI  - [Hepaticocholedoch reconstruction by explants and autotransplants].
AB  - Authors have elaborated new method of surgical correction of hepaticocholedoch
      strictures. The experiments were carried out on 25 mongrel dogs of both sexes
      with body weight 15-25 kg. The surgical procedures were done under endotracheal
      ether narcosis. The hepaticocholedoch stricture was induced preliminarily in all
      animals. After the modelling, stricture was cut out, the anatomical integrity of
      the common bile duct was restored by autovein (n=10) and "GORE-TEX" vascular
      prosthesis (n=10). The performed investigations have shown that autovenous
      transplant was subjected to incrustation by bile salts, later on it became
      necrotic. Therefore the autovenous transplant could not be used in biliary
      reconstruction. The results of biliary reconstruction by "GORE-TEX" vascular
      prosthesis were promising. The "GORE-TEX" vascular prosthesis is well adapting
      with bile ducts tissue and do not incrust by bile salts.

PMID- 16444051
TI  - Aspects of aging in georgian traditional medicine.
AB  - The goal of the investigation was studying Georgian medicinal manuscripts of X
      XVIII centuries in order to find out ideas of ancient authors regarding
      peculiarities of healthy lifestyle from the moment of birth till the elderly age.
      Results of analysis of Georgian medieval medicinal manuscripts allow us to
      conclude, that Caucasian longevity is determined not only by genetic, ecological,
      social and hygiene factors, but also by rational diet, proper treatment, remedies
      of plant origin and healthy lifestyle, existing in Caucasian cultural
      anthropology. Original schemes of diets and recipes, based on humoral theory and
      balanced by main characteristics of natural material are described.

PMID- 16444053
TI  - [Humoral mechanisms of autoimmune process against type I collagen in psoriasis].
AB  - Psoriasis represents disease with the involvement autoimmune mechanism against
      type I collagen, and its degree depends on the form of the disease and its
      clinical course. There is direct association between the autoantibody titres
      against type I collagen and the severity of the disease. As developed autoimmune
      process against type I collagen is specific in traditional treatment process, in
      spite of definite clinic effectiveness, without usage of specific factors there
      is no involution in autoimmune process against type I collagen. 134 patients with
      psoriasis have been investigated. 94 of them had vulgar psoriasis, 20 had
      erythrodermal form and 20 had arthropatic form. 50 healthy subjects were included
      in the control group. The age of patients varied from 20 to 70 years. It is
      confirmed that by treatment using miolophid immunomodulation autoantibody against
      type I collagen has decreased and treatment was relatively effective. It should
      be mentioned that despite immunomodulation therapy and achieved effect, there is
      no complete involution of autoimmune process, as in the case of psoriasis
      clinical and biological recovery periods do not coincide and thus after
      discharging from hospital prognosis must be controlled by measuring of
      autoantibody titres.

PMID- 16444052
TI  - [Peculiarities of NO-syntase expression in experimental hypertension caused by
      inhibition during low frequency laser irradiation of cardiovascular system and
      kidneys].
AB  - The aim of our study was the investigation of expression of NO-syntase
      endothelial (eNOS) and inducted (iNOS) forms in cardiovascular system and kidneys
      at experimental hypertension caused by laser irradiation. For investigation of
      experimental model of hypertension the rats of Vister species together with the
      drinking water were administered by L-NAME, NO inhibitor. Rats were divided into
      the following groups: in group I, irradiation with laser was started immediately
      after L-NAME administration, in group II - on the third day, in group III - on
      the 12th day, but in group IV - on the 28th day, respectively. The animals have
      been killed on the 10th day after irradiation. The morphological and
      immunohistochemical studies of heart and blood vessels (coronary arteries, aorta
      and kidney artery) and kidneys have been performed, with determination of eNOS
      and iNOS expression. The obtained results show that at irradiation by laser
      irradiation of low-frequency immediately after administration of L-NAME, eNOS
      expression is kept as in heart and blood vessels as in kidneys then iNOS
      expression is started firstly in myocardium and kidney (II group) and then in all
      studied blood vessels (III group). The mentioned facts prove that the irradiation
      by a laser of low - frequency inhibits eNOS inhibition after L-NAME action that
      must represent the background of antihypertensic effect after laser irradiation.
      Due to the results of study, an irradiation by a laser of low - frequency might
      be used for prevention of hypertension in preclinical stage to avoid the further
      complications, but its using with the aim to relieve the clinical evidences is
      not recommended.

PMID- 16444054
TI  - [Chromosome instability in patients with different forms of cardiomyopathy and
      their relatives].
AB  - Comparative studies on spontaneous and induced by two agents (mytomycin C and
      Nickel chloride) chromosome instability have been conducted in cultured
      lymphocytes derived from patients with hypertrophic and dilated forms of
      cardiomyopathy (HCMP and DCMP) and their relatives compiling a high-risk group to
      develop mentioned pathologies. In patients with HCMP and DCMP, as well as in
      their relatives higher levels of spontaneous chromosome instability were found in
      comparison with the control group (comprising healthy individuals without
      cardiomyopathic anamnesis). Almost all the affected patients and their relatives
      revealed tendency to increased aneuploidy and significant elevation of polyploidy
      when compared with control values. It was demonstrated that nickel chloride
      induced chromosome disorders registered more frequently in lymphocytes of the
      patients and their relatives than in cells of control subjects, but mytomycin C
      did not have such an affect. We assume to explain the similarity of studied
      parameters in patients with cardiomyopathy and their relatives as a consequence
      of identical rearrangements in genome functioning. The revealed analogy should be
      interpreted as a pre-illness condition for the individuals included in the risk
      group.

PMID- 16444055
TI  - [Oxidative stress as common pathological phenomenon and possibilities of its
      correction].
AB  - It was shown that disorders of oxidative metabolism play an important role in the
      pathological processes which develops at subcellular level -- disorder of
      electron transport at ubichinon-oxidoreductase locus of respiratory chain in
      mitochondria. The latter could be discussed as common pathological phenomenon
      determining oxidative stress. It is found that altered synthesis and metabolism
      of nitric oxide plays an important role in the pathogenesis of oxidative stress.
      It has been detected the ways and mechanisms of disorders of NO synthesis and
      conversion. The negative role of widespread and irrational use of antioxidant
      therapy and "universal" antioxidant treatment was characterized.

PMID- 16444057
TI  - Maternal genital bacteria and surface colonization in early neonatal sepsis.
AB  - OBJECTIVE: The study was intended to evaluate the role of maternal genital
      bacteria and baby's surface colonization in early onset neonatal sepsis. METHODS:
      Babies (born in the hospital of Jawaharlal Institute of Postgraduate Medical
      Education and Research) who developed clinical signs of sepsis were studied.
      Swabs were collected for culture from baby's umbilicus, ear, throat in addition
      to gastric aspirate and blood culture. The genital tract of the mother was also
      studied for bacterial colonization. The organisms isolated from the maternal
      genital tract and baby's surface colonization were correlated with those isolated
      from blood culture by calculating Phi correlation coefficient. RESULTS: Esch coli
      was the most common organism isolated from maternal genital tract and surface
      cultures of babies, but Klebseilla-Spp was the most common organism isolated from
      blood. There was a significant correlation between surface colonization of babies
      and maternal genital bacteria, so also was baby's surface culture and blood
      culture. However, correlation between maternal genital bacteria and baby's blood
      culture was not significant. CONCLUSION: Surface colonizing bacteria and not
      maternal genital bacteria are important in early onset neonatal sepsis.

PMID- 16444056
TI  - Neonatal morbidity and placental pathology.
AB  - OBJECTIVE: To investigate the association between gestational age, placental
      pathology and outcome among preterm births. METHODS: Medical records and
      placental pathology results of 165 preterm infants (gestational age pound 34
      weeks) were used to analyze the development of intraventricular hemorrhage (IVH),
      bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus
      arteriosus (PDA) and sepsis, in association with placental findings in the
      gestational age categories of 22-27 (n=71) and 28-33 (n=93) weeks. RESULTS:
      Significant differences were found in placental findings based on gestational age
      and neonatal morbidity. Lower gestational age was associated with increased
      infection-related lesions such as chorionic vasculitis (47.9%, P< 0.001) and
      acute chorioamnionitis (67.6%, P< 0.001). Placental lesions reflecting
      disturbances of fetal-placental blood flow (infarction, chorionic plate thrombi
      and basal perivillous fibrin) were predominantly seen in the 28-33 week
      gestational age category (P< 0.05-0.01). Despite the high prevalence of
      chorioamnionitis (38.8%), no significant association was found between this
      lesion and the tested preterm morbidity after controlling for gestational age.
      Only, villous edema and chorionic vasculitis were identified as independent
      predictors for the development of IVH (49.2%, ORA 2.57, 95% CI 1.01, 6.58 and
      39.3%, ORA1.95, 95% CI 1.01, 4.21, respectively). CONCLUSION: Villous edema and
      chorionic vasculitis are significant risk factors for the development of the IVH
      among neonates born at gestational age pound 34 weeks.

PMID- 16444058
TI  - Severe pneumonia in a remote hilly area: integrated management of childhood
      illness.
AB  - OBJECTIVE: This study aims to profile children with severe pneumonia in the
      perspective of Integrated Management of Childhood Illness (IMCI) strategy in a
      resource-constrained environment. METHODS: 115 consecutive children, aged 2
      months to 10 yr, hospitalized with severe pneumonia were prospectively evaluated
      between May 1997 and June 1998 at a civil hospital in the northern hilly state of
      India. RESULTS: All children had tachypnea and lower chest wall indrawing.
      Grunting was observed in 39.7%, inability to drink in 16.5%, and cyanosis in 1.7%
      cases. Radiological investigation was carried out only in 90 children that
      included abnormal chest radiographs (CXRs) in 76.6% cases. Feeding malpractices,
      vaccination inconsistencies, exposure hazards to smoking, micronutrient as well
      as macronutrient deficiencies, treatment from unqualified practitioners,
      inconsequential involvement of health care workers, predominant burden on mothers
      in the care of sick children, failure to recognize signs and symptoms of
      pneumonia by parents at home, lack of oxygen facilities, problems of
      accessibility and less faith on primary health care services were widely
      prevalent bottlenecks for effective implementation of 3 components of IMCI.
      CONCLUSION: Our study offers practical insights that can be useful in customizing
      IMCI to needs of children with pneumonia in a resource-constrained environment.

PMID- 16444059
TI  - Dehydration and hypernatremia in breast-fed term healthy neonates.
AB  - OBJECTIVE: The aim of the study was to determine the incidence of significant
      weight loss, dehydration, hypernatremia and hyperbilirubinemia in exclusively
      breast-fed term healthy neonates and compare the incidence of these problems in
      the warm and cool months. METHODS: During the study period 496 neonates were
      recruited. RESULTS: 157 neonates (31.6%) had significant weight loss (> 10 %
      cumulative weight loss or per day weight loss > 5%). Clinical dehydration was
      present in 2.2% of neonates. Of these 157 neonates, 31.8% had hypernatremia and
      28 % had hyperbilirubinemia. CONCLUSION: The incidence of the above mentioned
      problems were higher in the warm months but the difference was not statistically
      significant.

PMID- 16444060
TI  - Child survival and safe motherhood program in Rajasthan.
AB  - OBJECTIVE: This study was planned to evaluate the MCH services, particularly
      immunization in rural areas of the poor-performing state of Rajasthan. METHODS: A
      community-based, cross-sectional survey using the WHO 30 cluster technique was
      carried out as a field exercise by participants of 9th Field Epidemiology
      Training Programme (FETP) course by National Institute of Communicable Diseases
      (NICD) in rural areas of Alwar district of Rajasthan. RESULTS: Less than one
      third (28.9%) of children, aged 12-23 months, were fully immunized with BCG, 3
      DPT, 3 OPV and Measles vaccines; around a quarter (26.5%) had not received even a
      single vaccine (non immunized), and little less than half (44.5%) were found
      partially immunized. Around half of the eligible children were vaccinated for BCG
      (55.9%) and Measles (43.6%). Though nearly two-third (66.8%) were covered with
      first dose of DPT and OPV, but about one third of these children dropped out of
      third dose of DPT and OPV for various reasons. National Family Health Survey
      (NFHS) data also had revealed that BCG coverage was 64.3%; measles was 36.2%; and
      coverage by DPT 1, 2, 3 and Polio 1,2 and 3 were 64.4%, 57.0%, 46.6% and 77.5%,
      71.1% and 54.4% respectively in rural areas. The main reasons for drop-out or non
      immunization was "lack of information about the immunization programme" (41.3%).
      Though nearly all (more than 96%) of the children were immunized through
      Government established centers, but immunization cards/documents were made
      available only to 27.6% of children. CONCLUSION: The problem of low coverage and
      high drop-out rate of immunization could be overcome by creating awareness of the
      program and relevance of 2nd and 3rd doses of DPT and polio vaccines. Increasing
      community participation through intensive and extensive health education campaign
      should also be undertaken. Since most of the deliveries were done at home under
      the supervision of untrained midwives, training programme as well as involving
      them in IEC activities should be contemplated.

PMID- 16444061
TI  - Renal function and cardiac angiography.
AB  - OBJECTIVE: To study the effect of non-ionic contrast medium on renal function in
      children with cardiovascular disease. METHODS: Analysis of renal function in 98
      children with cardiovascular disease before and after the use of Iopamidol,
      Iohexol, and Ioversol was done for angiography. Serum creatinine (s-Cre), urinary
      N-acetyl-beta-D-glucosaminase (u-NAG), urinary beta 2-microglobulin (u-BMG), and
      urinary alpha 1-microglobulin (u-AMG) levels were evaluated. RESULTS: Although s
      Cre levels remained unchanged, u-NAG/Cre, u-AMG/Cre and u-BMG/Cre significantly
      increased 12 hours after angiography. Levels of u-NAG/Cre, u-BMG/Cre, and u
      AMG/Cre after angiography were significantly higher in neonates and infants (age<
      12-months, n=32) than in children (age>1-year, n=61), in patients with more than
      5 ml/kg of contrast medium (n=25) than in those with less than 5 ml/kg (n=70) and
      in cyanotic patients (n=13) than in non-cyanotic (n=80) patients. CONCLUSION:
      Transient renal tubular dysfunction occurred in all of these three non-ionic
      contrast mediums. Although renal tubular function was intact on a long-term
      basis, one should be careful of contrast medium-induced nephropathy, especially
      in neonates and infants, in patients receiving more than 5 ml/kg of contrast
      mediums in total, and in patients with cyanotic heart disease in using non-ionic
      contrast mediums.

PMID- 16444062
TI  - Hyperglycemic hyperosmolar nonketotic syndrome.
AB  - Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) was infrequently diagnosed
      till recently. Now it is being diagnosed with increasing frequency in obese
      children with type 2 diabetes mellitus (T2 DM) and its incidence is likely to go
      up, given global increase in incidence of childhood obesity, increased insulin
      resistance, and T2 DM. The syndrome is characterized by severe hyperglycemia, a
      marked increase in serum osmolality and dehydration without accumulation of beta 
      hydroxybutyric or acetoacetic ketoacids. Significant ketogenesis is restrained by
      the ability of the pancreas to secrete small amount of insulin. Prolonged phase
      of osmotic diuresis leads to severe depletion of body water, which excees that of
      sodium, resulting in hypertonic dehydration. These children, usually obese
      adolescents with T2 DM, present with signs of severe dehydration and depressed
      mental status but continue to have increased rather than decreased urine output
      and are at increased risk of developing rhabdomyolysis and malignant
      hyperthermia. Emergency treatment is directed at restoration of the intravascular
      volume, followed by correction of deficits of fluid and electrolyte (Na+, K+,
      Ca++, Mg++, PO4++), hyperglycemia and serum hyperosmolarity, and a thorough
      search for conditions that may lead to this metabolic decompensation and their
      treatment. Use of iso-osomolar isotonic fluid (0.9% saline) until hemodynamic
      stabilization initially, followed by 0.45% saline with insulin infusion at the
      rate of 0.1 units/kg/hour, addition of 5% dextrose in fluids and reduction of
      insulin infusion once the blood glucose is 250 to 300 mg/dl is generally
      recommended. However, evidence-based guidelines about composition and tonicity of
      fluids and electrolyte solutions for early resuscitation and rehydration, the
      rate of infusion-rapid vs slow, and insulin dose-low vs normal, in treatment of
      HHNS in children are awaited. Careful monitoring of glucose levels and ensuring
      adequate hydration in patients 'at risk' of HHNS, including those receiving
      medications that interfere with the secretion or effectiveness of insulin should
      decrease the risk of HHNS.

PMID- 16444063
TI  - Complementary foods associated diarrhea.
AB  - The World Health Organization regards illness due to contaminated food as one of
      the most widespread health problems in the contemporary world. Food safety
      especially in the weaning groups is one of the major concerns that have posed a
      threat to health of the children. Millions of children in the world die each year
      from diarrheal diseases; hundreds of millions suffer from frequent episodes of
      diarrhea and consequent impairment of nutritional status. Contaminated foods play
      a major role in the occurrence of diarrheal diseases. Apart from food
      contamination, transmission of infection occurs by direct contact, highly favored
      by the habits and customs of the people. Improper storage and handling of cooked
      food is equally responsible for food-borne illnesses, as during storage
      especially at ambient temperature (28-38 degrees C) there is the risks of
      multiplication of pathogenic organisms increase. Food safety education is a
      critical prerequisite and is an essential element in control and prevention of
      diarrheal diseases. However, no preventive measures can ever be successful
      without the acute involvement of the caretakers, other family members and the
      community. To sensitize the community in a catalytic manner, health workers,
      community leaders and community volunteers can act as effective change agent, to
      bring about a behavior that can lead to improvement in their real life practices,
      thereby reducing the prevalence of diarrheal episodes in young children. Food
      Safety Education Programs that involve volunteers are cost effective as they can
      be reached to a maximum number of people through limited health personnels, and
      by this, the community can be made responsible for its own health problems.

PMID- 16444064
TI  - Editorial--Growth and its disorders.

PMID- 16444065
TI  - Insulin like growth factors axis and growth disorders.
AB  - The growth hormone-insulin like growth factor (GH-IGF) axis plays a crucial role
      in the regulation of growth. Initially considered to be a mediator of growth
      hormone actions, IGF axis has been established as an independent endocrine system
      with wide array of actions. Recent advances have led to tremendous increase in
      the clinical utility of the IGF axis. IGF-based investigations (IGF1 and IGF
      binding protein 3) are now replacing GH-based investigations for evaluation and
      monitoring of disorders of the GH-IGF axis. IGF therapy has been successfully
      utilized in growth hormone insensitivity syndrome and GHD type 1B. The
      possibility of IGF axis as therapeutic options is being explored in wide variety
      of disorders like hypoxic-ischemic encephalopathy, Alzheimer's disease and
      psoriasis.

PMID- 16444066
TI  - Small for gestation and growth hormone therapy.
AB  - 3 to 10% of neonates are born small for gestation (SGA). This usually occurs
      because of intrauterine growth retardation (IUGR). After birth most SGA infants
      show good catch-up growth and normalize their height and weight. About 10% of
      them continue to remain short (<-2SD) and do not achieve normal adult height,
      resulting in psychosocial problems. The mechanism of short stature in these
      children is poorly understood. Infants who do not show catch-up growth usually
      have an alteration in the GH-IGF-I axis. Diagnostic and management criteria for
      short stature in SGA were ill-defined in the past. Growth hormone (GH) therapy
      for improving height in these children has been approved by the FDA. GH therapy
      leads to growth acceleration and normalization of height during childhood. Long
      term GH treatment normalizes adult height above -2 SDS in 85% children, and 98%
      achieve an adult height within their target height range. GH therapy is safe in
      SGA children, but it is important to monitor for side effects.

PMID- 16444067
TI  - Psychosocial effects of short stature.
AB  - The treatment of children with short stature was revolutionized by the creation
      of recombinant growth hormone therapy. While it cannot be denied that therapy
      adds significant height to children who are growth hormone deficient, such
      treatment is both painful, requiring many injections for years, as well as
      extremely expensive, both for the children's parents as well as for medical
      health care for society. With the indications for growth hormone treatment
      expanding over the years to include children with short stature who are not
      growth hormone deficient, it is important to determine all potential benefits
      beyond the obvious physical effects in order to make efficient cost-benefit
      determinations on appropriate usage of growth hormone therapy. One aspect of
      possible benefits for these children with short stature may be psychological
      features, such as increased overall happiness and self-esteem that is gained with
      increased height. A review and analysis of literature was undertaken in order to
      determine what effect, if any, growth hormone therapy has on short children's
      psychosocial well-being.

PMID- 16444068
TI  - Growth in precocious puberty.
AB  - Growth in precocious puberty is a subject of concern to families and clinicians
      alike. The definition of precocious puberty and the role of obesity in the age of
      onset have also been areas of debate since the Lawson Wilkins Society recommended
      a lowering of the age of onset of precocious puberty in US girls. An
      understanding of growth patterns in normal children with earlier or later onset
      of puberty and the variable rate of progression between individuals with central
      precocious puberty as well as the imprecision in available height prediction
      methods are important in assessing height outcomes in this condition. In the
      absence of randomised controlled trials in this area, only qualified conclusions
      about the effectiveness of interventions can be drawn. In general, it appears
      that height outcome is not compromised in untreated slowly progressive variants
      of central precocious puberty. In rapidly progressing central precocious puberty
      in girls, gonadotrophin releasing hormone agonists (GnRH agonists) appear to
      increase final height by about 5 cm in girls treated before the age of eight, but
      there is no height benefit in those treated after eight years. Scanly data is
      available to assess treatment effects in boys. GnRH agonists appear to be
      relatively safe. The decision to treat central precocious puberty should take
      into account rate of progression of pubertal changes as well as biochemical
      markers and may need to address other factors (for example psychosocial and
      behavioural issues) as well as height outcome.

PMID- 16444070
TI  - Salt wasting disorder in the newborn.
AB  - The clinical presentation of pseudohypoaldosteronism (PHA) mimics congenital
      adrenal hyperplasia (CAH). Poor response of the dehydration and electrolyte
      abnormalities to steroid therapy should make one suspect PHA. The treatment is
      supportive in the form of salt replacement and sodium resonium. We report a case
      of PHA that presented as salt wasting on the second day of life, initially
      appearing like CAH. The baby responded well to sodium resonium and salt
      replacement.

PMID- 16444069
TI  - Growth in congenital adrenal hyperplasia.
AB  - Individuals with congenital adrenal hyperplasia (CAH) are shorter, on an average,
      than the general population. A recent meta analysis of final height in CAH
      indicated that the height deficit is typically 1 to 2 standard deviations below
      the mean in both males and females. Growth in CAH due to 21-hydroxylase
      deficiency is influenced by a number of factors, related both to the underlying
      disease and its treatment. In general, males with the simple virilising form have
      the poorest height prognosis. This relates in part to late diagnosis and
      treatment and the bone age advancement seen in individuals with untreated
      postnatal androgen excess. Obesity in CAH patients also appears to be correlated
      with reduced height potential. Glucocorticoid treatment which is vital for
      cortisol replacement, prevention of adrenal crises and androgen suppression,
      results in growth inhibition when administered in larger doses. Current evidence
      suggests that infancy and peripubertal periods are the time periods where height
      outcome is most sensitive to glucocorticoid dose. More recent estimates of
      physiological cortisol secretion rates indicate that standard cortisol
      replacement schedules may result in overtreatment. In addition, dose titration to
      achieve complete androgen suppression and normalization of 17-hydroxyprogesterone
      is likely to result in overtreatment and consequent growth impairment.
      Optimization of current treatment may lead to further improvements in height
      prognosis. The potential benefits of more complex treatment regimes, using
      aromatase inhibitors and antiandrogens, in combination with a reduced
      glucocorticoid dose remain uncertain.

PMID- 16444071
TI  - Neonatal pseudohypoparathyroidism.
AB  - The case of a neonate is presented who had early onset seizure associated with
      hypocalcemia, hyperphosphatemia, and raised parathyroid hormone. The infant did
      not have any stigmata of pseudohypoparathyroidism. The hypocalcemia was initially
      resistant to calcium therapy, but responded to vitamin D analog therapy. The
      diagnosis of 'neonatal pseudohypoparathyroidism' was entertained; the infant
      remained stable and seizure-free with normal serum biochemistry during 3 months
      of follow-up.

PMID- 16444072
TI  - Wilson's disease presenting as respiratory failure.
AB  - Wilson's disease in an 11-year-old girl with generalized weakness and respiratory
      failure is reported. The child succumbed to severe hypokalemia refractory to
      therapy progressing to acute renal failure and death. This atypical presentation
      and course prompted this clinical brief.

PMID- 16444073
TI  - Hay-wells syndrome of ectodermal dysplasia.

PMID- 16444075
TI  - Display of feeding bottles in advertising renditions.

PMID- 16444074
TI  - Single vs multidrug therapy in enteric fever.

PMID- 16444076
TI  - Carers' perspective in quality of life in epilepsy.

PMID- 16444079
TI  - Is hydrocortisone really better?

PMID- 16444080
TI  - Weaning advice to mothers: a point to ponder over.

PMID- 16444081
TI  - Megaloblastic anemia in a child with central nervous system manifestations.

PMID- 16444083
TI  - Parental history of allergy, maternal serum IgE & cord serum IgE.
AB  - BACKGROUND: Allergic reactions are responsible for much illness, irritation and
      disquiet in the life of the child. Recognition and management of allergy in
      childhood is of great importance to prevent major allergic syndromes. AIM: To
      correlate cord serum IgE with parental history of allergy and maternal serum IgE.
      SETTINGS AND DESIGN: In consultation with the attending gynecologist a survey of
      950 pregnant women from different parts of Mumbai, visiting gynecology clinics
      was carried out. METHOD: 100 pregnant women were randomly recruited for the
      study. Allergic history of both the parents was collected. Blood samples of
      mothers and matched cord blood samples were collected. Total serum IgE levels
      were determined using solid-phase immunoradiometric assay. Total serum IgA from
      each cord blood sample was checked. OBSERVATION & RESULTS: (1) Positive
      correlation was observed between cord serum IgE and matched maternal serum IgE,
      with mothers having history of allergy. (2) There was no relation (P=0.99)
      between cord serum IgE and matched maternal serum IgE, where mothers had no
      history of allergy. (3) A significant elevation in cord serum IgE was found only
      with maternal but not with paternal history of allergy. (4) No elevation was
      found in cord serum IgE (0.5 IU/mL). (6) All cord serum samples had IgA< 0.06
      IU/mL ruling out the possibility of contamination with maternal blood.
      CONCLUSION: The maternal history of allergic disease is associated with an
      elevated cord serum IgE among newborns. Cord serum IgE is a simple, non-invasive
      and convenient test, which can supplement the maternal history to provide more
      discriminative information about the allergic status of the newborn.

PMID- 16444082
TI  - The impact of HIV/AIDS on the quality of life: a cross sectional study in north
      India.
AB  - OBJECTIVE: To determine the impact of Human Deficiency Virus (HIV)/Acquired
      Immunodeficiency Syndrome (AIDS) on the quality of life (QOL) on such patients in
      North India. DESIGN: A cross sectional study. SETTING: Outpatient setting and
      wards, Department of Medicine at a premier tertiary health care center, North
      India. PARTICIPANTS: Sixty-eight consecutive HIV/AIDS patients attending Medicine
      out patient department and/or admitted to the wards of All India Institute of
      Medical Sciences were administered a structured questionnaire by the HIV nurse
      coordinator. QOL was evaluated using the WHOQOL-Bref (Hindi) instrument.
      ANALYSIS: One way Analysis of Variance (ANOVA) was performed to find out
      significant difference between the clinical categories and socio-demographic
      variables on QOL domains. RESULTS: The overall QOL mean score on a scale of 0-100
      was found to be 25.8. Similarly, on the scale of 0-100 the mean scores in the
      four domains of QOL in descending order were social (80.9); psychological (27.5);
      physical (17.7) and environmental domain (11.65). There was a significant
      difference of quality of life in the physical domain between asymptomatic
      patients (14.6) and patients with AIDS (10.43) defining illnesses (p< 0.001) and
      asymptomatic and early symptomatic (12) patients (p=0.014). QOL in the
      psychological domain was significantly poorer in early symptomatic (12.1) (p<
      0.05) and AIDS patients (12.4) (p< 0.006) as compared to asymptomatic individuals
      (14.2). A significant difference in QOL scores in the psychological domain was
      observed with respect to the educational status (p< 0.037) and income of patients
      (p< 0.048). Significantly better QOL scores in the physical (p< 0.040) and
      environmental domain (p< 0.017) were present with respect to the occupation of
      the patients. Patients with family support had better QOL scores in environmental
      domain. CONCLUSIONS: In our study, QOL is associated with education, income,
      occupation, family support and clinical categories of the patients.

PMID- 16444084
TI  - Scorpion sting envenomation presenting with pulmonary edema in adults: a report
      of seven cases from Nepal.
AB  - Scorpion sting is a common problem in villages of Eastern Nepal. The life
      threatening complications of myocarditis and pulmonary edema is known in red
      scorpion in India but not reported in Nepal. This condition requires urgent
      attention and ICU care from few hours to days. Delay in recognition and the
      hypoxemia increase the morbidity and mortality. Illiteracy, ignorance, poverty,
      traditional faith healers trying treatment in remote areas, lack of transport in
      difficult terrains and the non availability of ventilation facility in nearby
      hospital, add to delay in appropriate treatment. Seven young adult patients
      admitted in a span of two years with history of scorpion sting presenting with
      pulmonary edema required ICU care. They were successfully managed with the
      positive pressure ventilation with PEEP, cardiac support with inotropes and fluid
      balance. Magnitude of problem, clinical presentation and management done is
      emphasized.

PMID- 16444085
TI  - Parkinsonism following a honeybee sting.

PMID- 16444086
TI  - Pseudo Meigs' syndrome with benign stromal hyperplasia and elevated CA-125.

PMID- 16444088
TI  - Non haematological effects of iron deficiency - a perspective.
AB  - Iron deficiency is a continuum beginning from lowering of tissue stores to the
      phase of exhausted tissue stores, interference with iron driven biochemical
      reactions in the body, microcytosis, hypochromia, increasing severity of anaemia
      with all its attendant consequences. Iron deficiency anaemia is a very well known
      concept but what is often not appreciated is the effect of broad canvas of iron
      deficiency on various tissues, organs and systems in our body in addition to iron
      deficiency anaemia leading to concept of "Iron deficiency disease". In this
      condition not only tissue delivery of oxygen is compromised but proliferation,
      growth, differentiation, myelinogenesis, immunofunction, energy metabolism,
      absorption and biotransformation are compromised leading to abnormal growth and
      behaviour, mental retardation, reduced cardiac performance and work efficiency,
      infection etc which ultimately leads to the concept that "iron deficiency not
      only breaks the machine but also wrecks the machinery."

PMID- 16444087
TI  - Mania associated with multiple paraphilias.

PMID- 16444089
TI  - [The effect of nasal dilators and local decongestants on the nasal airway].
AB  - OBJECTIVES: We evaluated the effect of external nasal dilator strips and local
      decongestants used either alone or in combination on the nasal airway. SUBJECTS
      AND METHODS: The study included 23 volunteer males (mean age 24.3 years; range 21
      to 36 years) with no complaints of nasal obstruction. Nasal airway dimensions
      were measured by acoustic rhinometry after the following applications: (i) no
      application; (ii) a placebo strip; (iii) a nasal dilator; (iv) a local
      decongestant; (v) a local decongestant followed by a placebo strip; and (vi) a
      local decongestant followed by a nasal dilator. Cross sectional areas (CSA1,
      CSA2, and CSA3) and three equal volumes (V1, V2, and V3) of the first 6 cm of the
      nasal airway were measured and compared with baseline values. RESULTS: After
      applying nasal dilator strips, CSA1 and CSA2 significantly increased by 33% and
      10%, respectively, with a significant increase in V1, whereas increases in V2 and
      V3 did not reach significance. The use of local decongestants was associated with
      significant increases in CSA1, CSA2, and CSA3 by 24%, 25%, and 18%, respectively,
      with a corresponding significant increase in V2 by 20%. Combined use of a local
      decongestant and nasal dilator resulted in significant increases in all areas and
      volumes compared with baseline values. CONCLUSION: Combined use of external nasal
      dilators and local nasal decongestants produces a cumulative effect on cross
      sectional areas and nasal cavity volumes.

PMID- 16444090
TI  - [The effectiveness of fiberoptic endoscopic swallow study and modified barium
      swallow study techniques in diagnosis of dysphagia].
AB  - OBJECTIVES: The purpose of this study was to evaluate the effectiveness of
      fiberoptic endoscopic evaluation of swallowing (FEES) and the modified barium
      swallow test (MBST) in patients with dysphagia. PATIENTS AND METHODS: Eighty
      patients with dysphagia were evaluated in three groups consisting of 27 patients
      with oral, pharyngeal, or esophageal masses; 26 patients with neurogenic
      dysphagia; and 27 patients with no distinct pathology. All the patients underwent
      FEES and MBST to examine elevation of the soft palate, nasal regurgitation,
      pharyngeal residue, penetration, aspiration, and pooling of secretions in the
      pyriform sinus and vallecula. RESULTS: In neurogenic dysphagia, MBST was more
      efficacious in detecting aspiration and pooling in the vallecula (p<0.05).
      Evaluation of the internal anatomy, visualization of masses, and
      laryngopharyngeal sensory discrimination were only possible with the FEES. On the
      other hand, evaluation of the elevation of the larynx and the hyoid, the
      relaxation of the upper esophageal sphincter, and the oral phase of swallowing,
      and the detection of esophageal pathologies were only possible with the MBST.
      CONCLUSION: The leading advantages of the two evaluation techniques seem to lie
      in the detection of aspiration for the FEES, and dynamic evaluation of the oral
      and esophageal phases of swallowing for the MBST.

PMID- 16444092
TI  - [A review of undergraduate ENT training programs in the light of the Core
      Education Program].
AB  - OBJECTIVES: The aim of this report was to evaluate the Core Education Program
      (CEP) and to contribute to the establishment of some national standards for
      undergraduate ENT training programs in medical schools. STUDY DESIGN: The
      documents of the national CEP for medical schools were reviewed. The lists under
      the titles of "Diseases-Condition-Symptoms," "Skills," and "Attitude and
      Behavior" were evaluated from the standpoint of ENT training. RESULTS: Of 396
      items listed under the domain of "Disease-Condition-Symptoms," 25 items were
      found to be related to ENT training. The essential skills to be achieved
      concerning ENT were ear, nose, throat, and neck examinations, ear lavage, nasal
      packing, and the Heimlich maneuver. Skills such as tuning fork tests,
      paracentesis, and measurement of noise were regarded as optional. CONCLUSION: The
      aim of the CEP is to determine the necessary level of knowledge and skills for a
      general practitioner. It should be adopted by all disciplines of medical schools
      and incorporated into education programs. The ENT society, Association, and study
      groups of education should collect feedback from ENT departments and convey all
      this to the CEP Study Group, which convenes every four years to re-evaluate the
      CEP in the light of the feedback received and recent developments in medical
      sciences.

PMID- 16444091
TI  - The effect of exercise on salivary IgA levels and the incidence of upper
      respiratory tract infections in postmenopausal women.
AB  - OBJECTIVES: To examine the patterns of upper respiratory tract infections (URTI)
      in postmenopausal Turkish women and the relationship of moderate aerobic exercise
      with secretion of salivary IgA and episodes of URTI. MATERIALS AND METHODS:
      Ninety healthy, sedentary women at ages 45 to 65 years volunteered to participate
      in a 12-week prospective study. They were randomized to three groups equal in
      number: indoor exercise, outdoor exercise, and no exercise. The exercising women
      were supervised during 30 min indoor treadmill walk or outdoor track walking
      sessions during 5 days/week at 60% of their calculated maximal heart rate. During
      a 12-week exercise program, episodes suggestive of URTI were recorded. Non
      exercising women were followed with weekly telephone calls. The salivary IgA
      levels were measured in all the subjects before and at the end of the study.
      RESULTS: There were significant differences between the exercising and non
      exercising women with respect to the number of URTI episodes and the length of
      URTI symptomatology per episode in favor of exercise. No significant difference
      was found between the indoor and outdoor exercising groups. The salivary IgA
      levels showed no significant differences between the three groups and within each
      group. CONCLUSION: Moderate intensity aerobic exercise is associated with fewer
      episodes of URTI and fewer days of URTI symptomatology per episode in healthy
      postmenopausal Turkish women, but this does not seem to be related to salivary
      IgA concentrations.

PMID- 16444093
TI  - Transoral microlaryngoscopic approach for schwannoma of the larynx.
AB  - Neurogenous tumors of the larynx are extremely rare. We present a 66-year-old
      male patient who underwent surgical excision of schwannoma of the larynx, which
      originated from the left aryepiglottic fold. Excision of the mass was performed
      through an endolaryngeal approach (suspension microlaryngoscopy). In the early
      postoperative period, the patient was breathing comfortably and his swallowing
      and phonation were normal. During a follow-up of three years, no evidence for
      recurrence was detected and he had no complaints of dysphagia, globus sensation,
      dyspnea on exertion, or cough.

PMID- 16444094
TI  - Basaloid squamous cell carcinoma of the larynx: a case report.
AB  - Basaloid squamous cell carcinoma (SCC) is a very rare, high grade, and aggressive
      variant of SCC, with a predilection for the upper aerodigestive system. Treatment
      should include surgery of the primary tumor and dissection of the cervical lymph
      nodes, followed by radiotherapy. We present a 50-year-old man with basaloid SCC
      of the supraglottic larynx, which was initially misdiagnosed as SCC. Supraglottic
      laryngectomy with bilateral radical neck dissection was performed, and
      radiotherapy was applied postoperatively. During a follow-up of 26 months, no
      evidence for recurrence was found. Basaloid SCC should be considered in the
      differential diagnosis of upper aerodigestive system malignancies because it has
      a distinct prognostic significance compared to conventional SCC.

PMID- 16444095
TI  - [Pulsatile tinnitus as the presenting symptom of dural arteriovenous fistula in
      two cases].
AB  - Pulsatile tinnitus associated with normal otoscopic findings may present as the
      only sign of a potentially life-threatening serious disease such as a dural
      arteriovenous fistula (dAVF) of the transverse or sigmoid sinus. If left
      untreated, dAVFs may lead to focal neurologic symptoms, intracranial
      hypertension, or hemorrhage, and finally to death. We report two cases of dAVF
      presenting with pulsatile tinnitus. Following diagnosis, both patients underwent
      transarterial embolization, after which their symptoms resolved.

PMID- 16444096
TI  - Metastatic pheochromocytoma of the thoracic spinal extradural space. Case report
      and review of the literature.
AB  - In this case report, a thoracic extradural metastatic pheochromocytoma without
      bony invasion, is presented. The disease which has been identified with its
      symptoms, bio-chemical features, radiological appearance, histological diagnosis
      has been discussed in comparison with malignant pheochromocytoma metastases in
      the literature. The origin of this tumor is the adrenal glands. Our review of the
      literature shows that tumor has primary metastasis in bony structures of the
      spine and then demonstrates secondary intraspinal invasion. This is the first
      case report of an epidural metastasis from malignant pheochromocytoma without a
      bony invasion.

PMID- 16444097
TI  - Successful treatment with defibrotide for sinusoidal obstruction syndrome after
      hematopoietic stem cell transplantation.
AB  - Sinusoidal obstruction syndrome (SOS) (formerly known as hepatic veno-occlusive
      disease (VOD)) is a life-threatening complication subsequent to hematopoietic
      stem cell transplantation. However, no completely satisfactory strategies for the
      treatment of SOS have been established yet. Defibrotide is a single-stranded
      polydeoxyribonucleotide with anti-thrombotic, anti-ischemic, anti-inflammatory
      and thrombolytic properties, but without systemic anticoagulant effects, and some
      encouraging results have been reported in western countries. We treated four
      patients with defibrotide for SOS, since there seemed to be no possibility to
      cure the patients with conventionally available treatments in Japan. All patients
      showed evidence of multiple organ failure at the start of the treatment.
      Defibrotide was administered intravenously in normal saline in four divided doses
      for 14 to 27 days. Three patients (75%) responded to the therapy, while one died
      of SOS and cytomegalovirus infection despite intensive therapy. None of the
      patients suffered from significant adverse effects such as severe hemorrhage.
      This is the first report dealing with the treatment with defibrotide of Japanese
      patients with SOS. Because defibrotide is considered to be promising for the
      treatment of SOS, it is important to start a phase II study as soon as possible.

PMID- 16444099
TI  - Is hyperbaric oxygen therapy effective for the management of chronic wounds?

PMID- 16444100
TI  - It's the way you ask that matters: comparison of data relating to prevalence of
      incontinence aid use from two surveys of people with multiple sclerosis.
AB  - The method used for data collection and research affects the outcomes and must be
      carefully considered when planning studies and when evaluating study results.
      This article presents the profound differences in outcomes generated by anonymous
      questionnaire vs face-to-face interviews. In this limited study regarding the use
      of incontinence aids among individuals with multiple sclerosis, the prevalence
      rates generated by questionnaire were 3 times the rates generated by interviews.
      Possible reasons for this discrepancy are addressed, and implications for
      research and for practice are identified.

PMID- 16444101
TI  - Get the LEAD out: noninvasive assessment for lower extremity arterial disease
      using ankle brachial index and toe brachial index measurements.
AB  - Lower extremity arterial disease affects approximately one third of individuals
      66 years of age and older and has a high risk for nonhealing wounds, infection,
      and limb loss. Much wound care is given by or under the direction of nurses.
      Therefore, the assessment and management of these patients presents many
      opportunities and challenges. Assessment is the cornerstone of effective care,
      but traditional methods of lower extremity arterial assessment, such as pulse
      palpation and pain history, are insufficient to determine the presence and extent
      of ischemia. Recently published national guidelines for assessment and management
      of patients with lower extremity wounds have recommended using noninvasive tests
      such as the ankle brachial index and toe brachial index to rule out lower
      extremity arterial disease, which complicates wound healing. However, the ankle
      brachial index can be falsely elevated in patients with diabetes and renal
      failure because of calcification of the arteries, which causes them to be
      incompressible. In these situations, it has been advised to obtain a toe pressure
      or toe brachial index because digital arteries are usually less affected by
      calcification. There is a paucity of data about the knowledge of principles and
      performance of the ankle brachial index/toe brachial index by nurses,
      particularly in the United States, using pocket-sized portable Doppler equipment.
      Therefore, the purpose of this article is to provide an overview and synthesis of
      relevant studies and published expert opinion regarding noninvasive arterial
      assessment using ankle brachial and toe brachial indexes as a basis for
      developing protocols for performing the tests and identifying gaps in research
      where further investigation is needed.

PMID- 16444102
TI  - Evidence-based nursing care management for the pregnant woman with an ostomy.
AB  - Pregnancy presents many problems without working through additional problems in
      coping with an ostomy. Yet many women with an ostomy do get pregnant and do
      deliver healthy babies. Evidence-based nursing is of the utmost importance, as
      there is little published information on this topic. Because of the scarcity of
      pregnant subjects within the ostomy category, most studies, by necessity, select
      a purposive subject base. Therefore, other information sources regarding nursing
      management of the pregnant woman with an ostomy take on considerably more
      importance. This article explores other forms of evidence that can be used in
      managing the care of pregnant ostomy patients and specifically how nurses can
      integrate various sources of information in designing an evidence-based nursing
      care plan. Nonpharmacologic forms of relaxation therapy, easily used by nurses,
      such as mindfulness-based stress reduction, guided imagery, and hypnosis, are
      also identified as some ways nurses can relieve anxiety and experiential stress
      associated with pregnancy in women who have an ostomy.

PMID- 16444104
TI  - Diet strategies used by women to manage fecal incontinence.
AB  - Fecal incontinence occurs in community-living women who are elderly, as well as
      younger women, particularly after vaginal childbirth. Little is known about how
      women manage fecal incontinence in their everyday lives. Ten women who had fecal
      incontinence for at least 1 year participated in an audio-taped interview in a
      phenomenological study. Diet modification was identified as a key strategy for
      managing fecal incontinence. Various food types were avoided, restricted, or used
      as remedies. The meanings that the women applied to the diet strategies for
      managing fecal incontinence had 4 themes: restricting diet and eating patterns,
      eating and dealing with the consequences, treating fecal incontinence with foods
      and fluids, and lacking therapeutic guidance regarding diet modifications for
      fecal incontinence. The results of this study suggest that the continence nurse
      specialist recognize the important role and meaning of diet as a self-care
      strategy for women with fecal incontinence and address diet in their assessment
      and management recommendations.

PMID- 16444107
TI  - A cognitive therapy approach to promote continence.
AB  - Both urinary and fecal incontinence are frequently occurring problems with costly
      consequences - physically, emotionally, and economically. General self-management
      strategies to promote continence, as well as behavioral and medical
      interventions, are often advocated. In this article, strategies based on a
      cognitive model are directed toward 2 overall goals: managing cognitions that are
      largely outside the individual's control while altering those within the
      individual's control, and improving management of continence with cognitive
      techniques. This approach expands and supports the behavioral and medical
      approaches to continence care. Nurses can use this comprehensive approach to
      increase the likelihood of positive continence outcomes.

PMID- 16444108
TI  - The psychometric testing of a urinary incontinence nursing assessment instrument.
AB  - OBJECTIVE: This study was conducted to examine the psychometric properties of the
      Capital Health Authority (CHA) Screening Tool. DESIGN: A correlational design was
      used to evaluate the interrater reliability and concurrent validity of the CHA
      Tool. Alpha coefficients were calculated as measures of internal consistency.
      SETTING AND SUBJECTS: Psychometric testing employed convenience sampling to
      select 12 nurses who work in homecare or geriatric assessment unit settings, and
      23 homecare recipients who were experiencing incontinence. INSTRUMENTS: The
      Stress Urge Incontinence Instrument and Urodynamic Patient Questionnaire were the
      criterion measures for concurrent validity of the CHA Assessment Tool. METHODS:
      Interrater reliability testing involved examination of nurse participants'
      ratings of the same 4 videotaped scenarios of a client reporting differential
      symptoms of incontinence. Concurrent validity was estimated after the
      administration of the CHA Tool and the Stress Urge Incontinence Instrument and
      Urodynamic Patient Questionnaire to homecare clients by the researcher. RESULTS:
      Correlational analyses revealed good validity and reliability of the urge (r =
      .81, p < .01, Cronbach's alpha = .83) and stress subscales (r = .78, p < .01,
      Cronbach's alpha = .66) of the CHA Tool. CONCLUSIONS: This research provides
      support for a short assessment tool that will benefit individuals experiencing
      urinary incontinence, their caregivers, and society through improved continence
      management. The appropriate management of urinary incontinence symptoms could
      prevent long-term care admissions.

PMID- 16444109
TI  - Pyoderma gangrenosum and leg ulcers associated with vasculitis: importance of
      addressing the underlying disease process when treating inflammatory wounds.

PMID- 16444115
TI  - Trust the process-but have one!

PMID- 16444116
TI  - An important perspective on the case manager's role.

PMID- 16444119
TI  - Workflow technology: the new frontier. How to overcome the barriers and join the
      future.
AB  - Hospitals are catching up to the business world in the introduction of technology
      systems that support professional practice and workflow. The field of case
      management is highly complex and interrelates with diverse groups in diverse
      locations. The last few years have seen the introduction of Workflow Technology
      Tools, which can improve the quality and efficiency of discharge planning by the
      case manager. Despite the availability of these wonderful new programs, many case
      managers are hesitant to adopt the new technology and workflow. For a myriad of
      reasons, a computer-based workflow system can seem like a brick wall. This
      article discusses, from a practitioner's point of view, how professionals can
      gain confidence and skill to get around the brick wall and join the future.

PMID- 16444117
TI  - Case managers' roles and functions: Commission for Case Manager Certification's
      2004 Research, Part I.
AB  - The Commission for Case Manager Certification (CCMC) conducted its third case
      managers' role and functions study in 2004. The purpose of this research was to
      validate the currency and relevancy of the certified case manager examination.
      The results of this study are shared in 2 parts of an article. Part I discusses
      the process the CCMC used for the development of the Case Manager's Role and
      Functions Survey Instrument (CMRFSI). The research leads to the identification of
      6 new essential functions and 6 new knowledge areas, which describe case
      management practice. These findings were based on the survey of a large national
      sample of practicing case managers. Part II continues the analysis of the survey
      results and focuses on identifying the empirical activity and knowledge domains
      of case management practice, using factor analysis. It also discusses the
      similarities and differences found among various subgroups of case managers who
      were compared on the basis of certain demographic variables. In addition, it
      summarizes future changes in the field of case management as perceived by those
      who participated in the study.

PMID- 16444121
TI  - Role transition from caregiver to case manager--Part II.
AB  - This two-part article explores the process of role transition as it pertains to
      nurses moving from roles of caregivers to roles of case managers. Part 1 of the
      article presented a theoretical model that demonstrated the interplay of
      significant factors in the process of role transition and discussed how this
      model could be used to examine nurses' experience of this transition. Part 2
      presents findings from a qualitative study involving interview and focus group
      data contributed by nurses who have made the transition from caregiver to case
      manager. Data point to specific tensions experienced by these nurses, which are
      associated with time-task orientation, interactions and relationships, business
      culture and objectives, and self-image and professional identity. Recommendations
      for preparing and supporting nurses through this role are also offered.

PMID- 16444122
TI  - Managing employee health and productivity after mass disasters: Preparing,
      recognizing, and responding to posttraumatic stress and other health issues--Part
      II.

PMID- 16444123
TI  - Recent medical management trends.

PMID- 16444125
TI  - Traumatic brain injury case study.

PMID- 16444126
TI  - Deriving cost savings while enhancing quality of care through effective case
      management in the acute care facility.

PMID- 16444127
TI  - The art and science of being a self-employed medical case manager.

PMID- 16444128
TI  - Monitoring patients' intake.

PMID- 16444136
TI  - Pioglitazone/metformin (Actoplus met).

PMID- 16444137
TI  - A new indication for gamma hydroxybutyrate (Xyrem) in narcolepsy.

PMID- 16444141
TI  - The early history of Pediatric - Endocrinology.

PMID- 16444152
TI  - Thyroid hormone biosynthesis - the importance of the sodium/iodide symporter
      (NIS).

PMID- 16444153
TI  - Congenital hypothyroidism and iodine status in Turkey: a comparison between the
      data obtained from an epidemiological study in school-aged children and neonatal
      screening for congenital hypothyroidism in Turkey.
AB  - BACKGROUND: Congenital hypothyroidism and endemic iodine deficiency are the most
      common cause of mental retardation. However in both cases retardation is of
      nonpreventable nature. OBJECTIVE: The aim of the study was to investigate whether
      epidemiological study in school-aged children or neonatal screening of congenital
      hypothyroidism (CH) was useful to assess iodine status and monitor the preventive
      measures of iodine deficiency disorders (IDD). SUBJECTS: To study the
      epidemiology, 1046 school children, aged 8 to 12 years from 23 primary schools in
      rural and urban areas from three cities in Turkey were included. Neonatal
      screening for congenital hypothyroidism (CH) was carried in. METHODS: Goiter and
      thyroid volume were assessed by palpation and ultrasound, respectively. Thyroid
      stimulating hormone (TSH), total thyroxine (T4), and urinary iodine excretion
      (UIE) were measured. Neonatal screening for CH was adjusted according to the
      guidelines of Pediatric Endocrinology of the European Society for Pediatric
      Endocrinology. RESULTS: There was no significant difference between the median
      TSH in school-aged children and the cities of Bolu and Duzce (p>0.05). Median TSH
      of Zonguldak was significantly different from the median TSH of Bolu (p=0.046)
      and Duzce (p=0.028). There was no significant difference between the median T4
      levels of Bolu and Duzce (p>0.05). The median T4 of Zonguldak showed a
      significant difference from the median T4 value of Bolu (p=0.018), but an
      insignificant difference from the median T4 of Duzce (p>0.05). The overall goiter
      prevalence in 1046 children was 52%. In two years, 18606 newborns were screened.
      With a cut-off point at TSH >20 microm U/ml, the recall rate was 1.6% and the
      incidence of CH 1/2326. There was 26.7% children with TSH >5 microm U/ml. Both
      data of the epidemiological study in school-aged children and neonatal screening
      for CH indicated that the West Black Sea Region is affected by mild to moderate
      iodine deficiency. CONCLUSION: the implementation of neonatal screening for
      congenital hypothyroidism using TSH measurement has many advantages. It can
      detect congenital hypothyroidism and transient primary hypothyroidism, and can
      also be used for monitoring tools of preventive measures of IDD. Countries, such
      as Turkey, which has not begun national screening for CH yet, should make
      implementation of neonatal screening for CH using primary TSH measurement a
      political priority.

PMID- 16444154
TI  - Consequences of iodine deficiency and preventive measures.
AB  - Iodine Deficiency Disorders (IDD) can be prevented by an adequate intake of
      iodine in the population. Monitoring and evaluation are the most important phases
      of an IDD control program. The consequences of iodine deficiency are goiter and
      subclinical/clinical hypothyroidism in pregnancy. The deficiency is an important
      risk factor for brain damage and motor-mental development in the fetus, the
      neonate and in the child. In order to assess IDD, control programs should be
      developed, followed up and evaluated. The recommended methods of assessing status
      are; assessment of the goiter rate, measurement of urinary iodine concentration,
      determination of thyroid hormone levels and of thyroglobulin. Although adequate
      technology exists, elimination programs for IDD have not been successful until
      recent years. The most important issue at present is the long-term sustainability
      of salt iodization programmes. Alternative strategies are also needed for
      iodization in areas where iodized salt will not be available in the foreseeable
      future.

PMID- 16444156
TI  - Neonatal thyroid screening: methods-efficiency-failures.
AB  - Newborn screening for congenital hypothyroidism (CH) is one of the major
      achievements of preventive medicine, as the condition occurs frequently (1/4000
      newborns) and results in brain damage if not detected and treated in the first
      few days of life. Measurement of T4 and/or TSH in dried blood spots collected on
      the second through fifth days of life are the most widely used methods in
      screening programs for CH currently. Some children with the disease may be missd
      in any screening program, however, owing to factors related to the disease itself
      and the methods employed in its detection, as well as factors ascribed to the
      element of human error, ie screening errors. The methods employed in newborn
      screening programs for CH, their efficiency in disease detecetion, and biological
      factors as well as screening errors leading to missed cases are discussed.

PMID- 16444155
TI  - Thyroid function in pregnancy - maternal-fetal relationship in health and
      disease.
AB  - The article reviews the changes in maternal and fetal thyroid function during
      pregnancy. During the first trimester the fetus is dependant on maternal
      thyroxine and later on the direct supply of iodine from the mother for its own
      thyroxine production. The placental deiodinase metabolism provides the fetus with
      additional iodine and protects the fetus from excessive iodothyronine transfer
      and enables the development of its own hypothalamic pituitary thyroid axis.
      Maternal and fetal hypothyroxinemia can lead to irreversible CNS damage. In
      autoimmune thyroid diseases immunoglobulins and goitrogenic drugs can cross the
      placenta and affect the fetal thyroid. Therefore, careful monitoring of maternal
      iodine supply, even in areas with mild to moderate iodine deficiency as well as
      iodine FT4 before and during pregnancy, and avoidance of unnecessary goitrogenic
      drugs is mandatory for optimal fetal growth and development. In cases where fetal
      hypothyroidism is diagnosed, intraamniotic T4 treatment is suggested.

PMID- 16444157
TI  - Congenital hypothyroidism clinical aspects and late consequences.
AB  - Congenital hypothyroidism (CH) is the commonest treatable cause of mental
      retardation. The prevelance is 1/3000 - 1/4000 live births worldwide. The
      importance of CH is that, the longer the diagnosis of CH is delayed, the higher
      the risk of mental retardation and neurologic sequale; such as poor motor
      coordination, ataxia, spastic diplegia, muscular hypotonia, strabismus, learning
      disability and diminished attention span. The most common cause of permenant CH
      is thyroid dysgenesis (85-90%) in which the transcription factors TTF1,TTF2 and
      PAX8 would appear to be obvious candidate genes in the aetiology. Especially
      cardiac defects and some other birth defects are described in patients with CH.
      Inborn errors of thyroid hormonogenesis are responsible for 10-15% of CH cases
      and usually have autosomal recessive inheritance, consistent with a single gene
      mutation. Transient CH is very common in prematures with an estimate of 10% of CH
      babies identified on newborn screening, or 1 in 40,000 neonates. CH neonates are
      usually symptom-free and the most encountered symptoms are prolonged jaundice,
      large fontanelles and umbilical hernia. In general, the extent of clinical
      findings depends on the cause, severity and duration of hypothyroidism. An
      elevated TSH>20 microm Iu/L and a decreased concentration of T4 confirms the
      diagnosis of CH. Infants with permanant abnormalities of thyroid function mostly
      have a serum TSH concentration > 50 microm Iu/L. Ultrasonography, thyroid
      scintigraphy, bone x ray of the knee and serum thyroglobulin concentration are
      the other essentials after diagnosis to clarify the status of the thyroid and the
      severity of hypothyroidism. The higher doses of 10- 15 microm g/kg/day and the
      commencement of treatment before 2 weeks gave rise to better long term outcome of
      CH patients. In the follow up of the patients noncompliance is the most important
      problem and serum freeT4 or T4 and TSH should be obtained at each visit to adjust
      the doses of L-thyroxine. Still a small number of patients with severe
      hypothyroidism in utero or reflected by clinical signs and symptoms extremely low
      T4 levels and delayed bone age may have intellectual deficits despite normal
      intelligence.

PMID- 16444158
TI  - Thyroid Hormone Resistance in children.
AB  - Thyroid Hormone Resistance (RTH) is characterized by the diminished response of
      thyroid hormone-responsive tissues in varying degrees in association with
      elevated serum levels of total and free T4 and T3 and inappropriately normal or
      elevated TSH levels. In almost all cases it is due to different mutations in only
      one allele of the thyroid hormone receptor beta gene which blocks the action of
      normal allele thus producing dominantly inherited RTH. In RTH, varying degrees of
      target tissue responsiveness result in a heterogenous clinical presentation.
      Resistance in the thyrotrophs and the peripheral tissues is assessed by the
      evaluation of TSH secretion and changes in peripheral markers of thyroid hormone
      action after administration of L-T3, respectively. The treatment decision depends
      on the individual characteristics of each patient. Patients with hypothyroid and
      hyperthyroid symptoms may require treatment with thyroid hormone and with agents
      such as beta blockers, antithyroid drugs and thyroid hormone analogues.

PMID- 16444159
TI  - Pendred syndrome.
AB  - Pendred Syndrome, first described in 1896, is phenotypically characterized as the
      coexistence of sensorineural deafness and enlarged goiter with elevated iodine
      discharge after perchlorate administration. In 1996 the syndrome was mapped to
      chromosome 7 and the following year, the responsible gene was cloned and
      mutations were identified. The gene, pds, codes for a 780 amino acid protein,
      pendrin, which functions as an ion transporter. Located on the apical membrane of
      thyrocytes, it appears to be responsible for the transport of iodide out of the
      cell into the colloid where iodination of thyroglobulin occurs, catalyzed by the
      enzyme thyroid peroxidase. In the absence of the transporter, apical iodide
      transport is defective and thus organification of iodide is defective, the
      hallmark of Pendred Syndrome. However, organification is only partially
      deficient, even in the complete absence of pendrin, suggesting that other, as yet
      undefined, mechanisms exist that can partially compensate for lack of the
      protein. The pathophysiology of the hearing loss associated with Pendred syndrome
      is less well understood. Animal studies suggest that abnormal transporter
      function may cause abnormal endolymphatic pressure or composition and this
      results in secondary degeneration of sensory cells and in structural changes of
      the inner ear. This mechanism, although yet to be proven, suggests the intriguing
      possibility that early diagnosis and intervention could perhaps prevent at least
      some of the hearing loss.

PMID- 16444160
TI  - Hashimoto's Thyroiditis.
AB  - Hashimoto's Thyroiditis (HT) is the most common cause of thyroid diseases in
      children and adolescents and it is also the most common cause of acquired
      hypothyroidism with or without goiter. The linkage between HT and some HLA genes
      has been reported and a genetic predisposition to thyroid autoimmunity is
      suggested by observations in twins. There is no direct evidence that infections
      cause HT in humans, while iodine and iodine containing drugs can precipitate HT
      in susceptible populations. There is an infiltration of lymphocytes and plasma
      cells between the follicles followed by their atrophy. The clinical course is
      variable and spontaneous remission may occur in adolescence. Goiter, menstrual
      disorders, short stature, constipation, nervousness and exophthalmos have been
      reported as the most recurrent clinical features of HT. Nevertheless we studied
      33 patients with HT, 22 girls and 11 boys aged 4.9-19 years and most of them were
      euthyroid clinically. Hashimoto thyroiditis is often associated with type 1
      diabetes and other autoimmune disorders such as coeliac disease, type 2 and type
      3 polyglandular autoimmune disorders. Girls with Turner syndrome may develop HT.
      Patients with HT have positive antibodies to thyroglobulin and/or to
      thyroperoxidase in blood. Thyroid function could be normal or abnormal (overt
      hypothyroidism, subclinical hypothyroidism and hyperthyroidism). Abnormal
      ultrasound patterns may be present in patients with HT disease as diffuse
      hypoechogenicity and pseudonodules. L-thyroxine therapy is indicated in HT with
      hypothyroidism, but periodic re-evaluations are required because HT could be a
      self-limited disorder in some cases.

PMID- 16444161
TI  - The management of hyperthyroidism in children with emphasis on the use of
      radioactive iodine.
AB  - Graves' disease is the most common form of hyperthyroidism in childhood. Current
      treatment options include antithyroid medications, surgery, and radioactive
      iodine. Medical therapy is generally associated with long-term remission rates of
      less than 25% and a small risk of serious adverse reactions that include hepatic
      failure and bone marrow suppression. Total thyroidectomy is associated with very
      high cure rates and a small risk of hypoparathyroidism and recurrent laryngeal
      nerve damage. When radioactive iodine is used at appropriate doses, there is a
      very high cure rate without increased risks of thyroid cancer or genetic damage.
      Because of the theoretical risk of thyroid cancer after thyroid irradiation in
      individuals less than 20 years of age, relatively high doses of radioactive
      iodine should be administered to minimize residual thyroid tissue.

PMID- 16444162
TI  - Ophthalmic complications in juvenile Graves' Disease - clinic and therapeutic
      approaches.
AB  - Graves' Disease (GD) is the most common cause of juvenile thyrotoxicosis in
      children and adolescents. Regarding its treatment, there are wide differences
      between individual physicians' regimes and those of physicians in different
      countries. While Antithyroid Drugs (ATDs) remain the initial treatment of choice
      in almost all the medical centers in Europe, with surgery used mainly to deal
      with antithyroid failures, there is increasing interest, especially in US, in the
      use of radioiodine. Although there are data reporting no significant increase in
      thyroid neoplasia or gonadal injury in older children and adults receiving
      outpatient doses of radioiodine, endocrinologists and parents continue to shy
      away from this therapy, especially in Europe, in young children. Nor is there any
      increase in congenital abnormalities in the offspring of the adults. Thyroid Eye
      Disease (TED) is one of the most common manifestations of GD, the pathophysiology
      of which is not very well understood. However, studies by several investigators
      have begun to shed light on the many complex factors contributing to the
      development of ocular symptoms in TED. Thyroid ophthalmopathy in juvenile GD is
      more common but less severe and more likely to remit completely. Steroids and
      decompression surgery will very rarely be needed in early childhood. It has to be
      kept in mind that prolonged prednisone administration, which should be used in
      some severe cases of TED, is associated with weight gain, immune suppression and
      growth failure in children. Recent studies have shown successful therapy with the
      long-acting somatostatin analogues (SM-a), octreotide and lanreotide in adult
      patients with active TED. The rationale of this therapy is based on recent
      studies in which somatostatin receptors have been identified within the orbital
      tissues in TED, both in vitro and in vivo. We recently had the opportunity to
      treat 3 adolescents with moderately severe TED with SM-a. All had increased
      clinical activity scores (CAS) and were euthyroid on ATD at the time of
      initiation of treatment. They received 20 mg octreotide (sandostatin- LAR) i.m.
      one injection every 30 days for 4 months. Their ophthalmopathies improved
      substantially and CAS decreased in all the patients. In view of the encouraging
      therapeutic results in these 3 pediatric patients, SM-a may prove to be a
      valuable treatment in juvenile ophthalmopathy and a good alternative to
      corticosteroids. The results using SM-a in the treatment of TED seem promising,
      but studies with larger numbers of patients are needed before we reach any final
      conclusions.

PMID- 16444163
TI  - Differentiated thyroid cancer in childhood: pathology, diagnosis, therapy.
AB  - The incidence of thyroid cancer in childhood amounts to approximately
      0,5/100.000/year. However, after exposure to ionizing irradiation, the incidence
      may increase more than 20 fold. In children, lymph node metastases of
      differentiated thyroid cancer are frequent (more than 50%); distant metastases
      mainly to the lung are seen in 20-30%. The method of choice for the primary
      diagnosis of thyroid cancer today is ultrasonography with 7,5 - 10 MHz probes,
      accompanied by fine-needle aspiration biopsy. Differentiated thyroid cancer has
      to be treated with a multidisciplinary approach comprising total thyroidectomy
      and lymph node dissection, post-operative radioiodine treatment and TSH
      suppression by levothyroxine. The long-term results of this treatment approach
      are generally good with 10-year survival rates of 95% and higher. The treatment
      of children with disseminated pulmonary metastases however, may be complicated
      due to the increased risk of the induction of pulmonary fibrosis by radioiodine.

PMID- 16444164
TI  - Imaging of the normal and affected thyroid in children with emphasis on
      sonography.
AB  - In the past 15 years sonography (US) has become the most important imaging
      modality for the study of the thyroid gland. Thyroid pathologies are classifiable
      into congenital, diffuse and nodular diseases. US easily assesses congenital
      conditions such as agenesis or dysgenesis of the gland, although it may fail in
      demonstrating an ectopic gland. In diffuse diseases (Graves' disease and
      Hashimoto's disease) is a useful tool in assessing and subsequently monitoring
      the course of the disease. In thyroid nodular diseases, US main role is to
      localize nodules, to differentiate solid from cystic and partially cystic
      structures, and to look for other clinically unknown nodules in the gland.
      However it can be difficult to determine with US alone whether a nodule is benign
      or malignant.

PMID- 16444165
TI  - Interactions between the thyroid hormones and the hormones of the growth hormone
      axis.
AB  - The normal secretion and action of the thyroid hormones and the hormones of the
      GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent.
      Their interactions often differ in man from animal studies in rodents and sheep.
      Thus neonates with congenital hypothyroidism are of normal length in humans but
      IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I
      secretion and action depends on an euthyroid state. Present knowledge on the
      interactions between the two axes is reviewed in states of hypo- and
      hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as
      the relationship between IGF-I and thyroid cancer. Emphasis is given to data in
      children and aspects of linear growth and skeletal maturation.

PMID- 16444166
TI  - Drugs and thyroid interaction.
AB  - Compounds that effect thyroid function and their mechanisms of action are
      discussed in this review. Drug effects on laboratory test results should always
      be considered when interpreting laboratory results. Careful monitoring is
      required to identify and correct potential drug interactions.

PMID- 16444167
TI  - Recent advances in thyroid research: selective thyroid hormone receptor
      modulators (STRMs).
AB  - Compounds have been designed and tested exhibiting some of the beneficial effects
      of thyroid hormones, such as lowering of cholesterol and weight reduction,
      without the adverse thyroid hormone action on heart rate. Progress has also been
      made in attempting to treat hyperthyroidism by synthesizing antagonists that
      block thyroid hormone action, at the level of the thyroid hormone receptor or of
      the thyrotropin receptor. Clinical trials are still awaited, however, to verify
      whether these potentially promising agents will indeed prove to be of clinical
      therapeutic value.

PMID- 16444169
TI  - Adiponectin, an adipocyte-derived hepatic insulin sensitizer regulation during
      development.
AB  - A large body of clinical data, supported by genetic and pharmacological evidence,
      has demonstrated potent insulin-sensitizing effects of the adipocyte-derived
      secretory factor adiponectin. In adults, plasma adiponectin is generally
      negatively correlated with BMI and positively correlated with systemic insulin
      sensitivity. Only a limited number of studies have been performed in newborns,
      children and adolescents. Here we summarize the results from these recent
      findings in younger cohorts and discuss these results in context of the much
      vaster literature on adiponectin levels in lean, obese and diabetic adults.

PMID- 16444171
TI  - Insulin and human obesity.
AB  - The prevalence of obesity among modern communities increases dramatically and
      trends to achieve the characteristics of an epidemic. Obesity is the result of a
      sedentary life style and increased food intake, which characterises western
      communities. Obesity is closely related to insulin resistance and
      hyperinsulinemia and the very frequent combination of obesity and NIDDM is
      characterised as "Diabesity". The behaviour of man in seeking food and the amount
      of food consumption is a complicated situation, which is regulated by the CNS and
      especially in the arcuate nucleus of the hypothalamus. A repertoire of
      neurohormonal actions, generated in peripheral tissues and integrated in the CNS,
      encompasses many peptides with orexigenic and anorexigenic actions. Two main
      hormones, insulin and leptin, accomplish the fine-tuning of these peptides action
      at the critical level of body weight and energy control. The high prevalence of
      insulin resistance and hyperinsulinemia in obesity indicates a causative
      relationship between these two situations. It seems likely that insulin
      resistance in muscle cells is the prime "defect" which renders individuals
      vulnerable to obesity. The high prevalence of insulin resistance, about 25%,
      among otherwise healthy subjects indicates that this genetically determined
      "defect" may be the result of an evolutionary selection which rendered mankind
      capable of surviving during long periods of famine, in his long journey from the
      hunter-gatherer period of his life to the present time of plenty.

PMID- 16444170
TI  - Ghrelin: from a GH-secretagogue to the regulation of food intake, sleep and
      anxiety.
AB  - Grhelin is an endogenous ligand for the growth hormone secretagogue receptor from
      the stomach. It is a 28-aminoacid peptide of which the serine 3 residue is n
      octanoylated. Ghrelin strongly stimulates GH secretion in vivo as well as in
      vitro. This endogenous ligand promotes the production of orexigenic neuropeptides
      (NPY and AgRP) in the hypothalamic arcuate nuclei and activates the neurons that
      produce these orexigenic peptides, resulting in an increase in feeding and body
      weight. Ghrelin has other significant actions, including control of acid
      secretion, influences on sleep and on the regulation of anxiety.

PMID- 16444172
TI  - Increasing incidence of childhood obesity.
AB  - Childhood obesity is a nutritional, metabolic and endocrine disease; all of these
      factors have genetic components. Attractive for writers and painters, it has been
      found to be a medical risk. Childhood obesity had been neglected until about 30
      years ago. A series of cross-sectional and longitudinal studies performed in many
      countries using mainly BMI values as determinant of overweight have shown that
      there is an overall fast rise in overweight in many populations, usually starting
      around age 7. In certain populations and ethnic groups the rise and degree of
      obesity are especially high, such as the Hispano-Black and Native Americans and
      European countries. School children in the US, Greece, Ireland and Portugal are
      more overweight than those in 12 other countries. In addition to genetic factors,
      rapid changes in life style (more energy intake and less energy output) are the
      major factors causing childhood obesity. In recent years it has been recognized
      as a fast increasing public health problem.

PMID- 16444173
TI  - Prevalence and trends of obesity in children and adults of South Europe.
AB  - Obesity is an epidemic phenomenon in both developed and developing societies. In
      the majority of South European countries, obesity prevalence is high among
      children and adolescents while, in adults, epidemic proportions are found in
      Greece, Portugal and the Southern areas of Spain and Italy, with particular
      prevalence of abdominal obesity. Secular trends also show increasing rates during
      the last 20 years mostly among young children and among males in adulthood. In
      some countries such as Spain and Greece, nutrition transition contributed largely
      to the increase of obesity prevalence. Other particular predisposing factors are
      sedentary behaviours, variations of socio-economic status and probably the warm
      climate. Genetic factors could also play a role. Preventive and treatment
      strategies are urgently needed to stop the obesity epidemic in children of
      Southern European countries.

PMID- 16444174
TI  - Do obese children become obese adults: childhood predictors of adult disease.
AB  - Obesity is a multifactorial disorder influenced by genetic, behavioral,
      environmental and cultural factors. The prevalence of overweight and obesity in
      young people is increasing rapidly in both the developed and developing world and
      are considered today as a global epidemic. Recent studies show that obesity in
      adult life is heralded at birth and factors such as birth weight, adiposity
      rebound, socioeconomic status, early maturation and genetic predisposition may
      have a significant effect on the propensity to develop obesity in adulthood.
      Avoidance of accelerated weight gain in children should be investigated as a toll
      of adult obesity prevention.

PMID- 16444175
TI  - Prevalence of overweight and obesity among children and adolescents in
      Thessaloniki-Greece and Kayseri-Turkey.
AB  - The aim of this study was to investigate the prevalence of overweight and obesity
      among children and adolescents in the city of Thessaloniki, Greece and in the
      Kayseri area of Turkey and compare the results. For this purpose, data concerning
      the weight and height of 2458 Greek school children aged 6-17 years (1226 6-10
      years, 1232 11-17 years) and 3703 Turks (1032 6-10 years, 2671 11-17 years) were
      collected. BMI was calculated. The prevalence of overweight Greek schoolchildren
      was 22.2% while that of Turks was 10.6%. The obesity prevalence was 4.1% and
      1.6%, respectively (total overweight and obese children 26.3% and 12.2%,
      respectively). In the analyses, the estimations of the prevalence of overweight
      and obesity are based on the international BMI percentile curves and cut-off
      points in subjects aged 2-18 years recently established. A significant gender
      difference was found, males being more overweight and obese compared to females.
      Finally, the prevalences for both Greeks and Turks were higher in children when
      compared to adolescents. In conclusion, Greece (as represented by the
      Thessaloniki area) has one of the highest prevalences of overweight
      schoolchildren recorded in Europe while Turkey (as represented by Kayseri area)
      one of the lowest recorded among developed and developing countries. Differences
      in lifestyle and socioeconomic status in the two regions are most probably
      responsible for these results.

PMID- 16444176
TI  - Obesity and gonadal function of women.
AB  - Excessive visceral adiposity is associated with metabolic and reproductive
      abnormalities. Adipose tissue is an active endocrine gland and participates in
      multiple mechanisms in the reproductive function of women. The nature of the
      complex interaction of obesity with the female reproductive function remains a
      challenge. Several links have been implicated in the gonadal dysfunction of obese
      women, like insulin resistance and hyperinsulinemia, via which ovarian androgen
      production is stimulated resulting in hyperandrogenemia, increased peripheral
      aromatization of androgens to estrogens, altered gonadotrophin secretion,
      decreased sex hormone binding globulin, decreased GH and IGFBPs, increased leptin
      levels and altered neuroregulation of the hypothalamic-pituitary-gonadal axis.
      The impact of obesity in these mechanisms and their influence on female
      reproductive function are discussed in this article.

PMID- 16444177
TI  - The prevention of obesity in children.
AB  - A dramatic increase in the prevalence of overweight and obesity among children in
      Europe has occurred in the last twenty years, especially the last ten years. The
      number of overweight children is increasing in the EU by at least 400,000 every
      year, of which 85,000 are obese. Prevention of further cases is a priority, but
      the evidence base for child obesity prevention is limited in scope and provides
      only a few general observations. Prevention will probably require policies that
      affect not only the family and the school but also affect the wider social
      context, such as controls on marketing to children and improved safety in the
      built environment. Scientists and physicians can help to influence policy makers
      through their professional organisations.

PMID- 16444178
TI  - Cardiac autonomic nervous system activity in obesity.
AB  - The development of obesity is caused by a disturbance of energy balance, with
      energy intake exceeding energy expenditure. As the autonomic nervous system (ANS)
      has a role in the regulation of both these variables, it has become a major focus
      of investigation in the fields of obesity pathogenesis. The enhanced cardiac
      sympathetic drive shown in most of the studies in obese persons might be due to
      an increase in their levels of circulating insulin. The role of leptin needs
      further investigation with studies in humans. There is a blunted response of the
      cardiac sympathetic nervous system (SNS) activity in obese subjects after
      consumption of a carbohydrate-rich meal as well as after insulin administration.
      This might be due to insulin resistance. It is speculated that increased SNS
      activity in obesity may contribute to the development of hypertension in
      genetically susceptible individuals. It is also speculated that the increase in
      cardiac SNS activity under fasting conditions in obesity may be associated with
      high cardiovascular morbidity and mortality.

PMID- 16444179
TI  - Growth in disorders of adrenal hyperfunction.
AB  - This article reviews how growth is affected in disorders of adrenal
      hyperfunction. Growth is disturbed by adrenal hypersecretion of androgens or
      cortisol. Adrenal androgens, when in excess, lead to advanced linear growth and
      skeletal maturation, and prolonged hypercortisolemia leads to the suppression of
      growth hormone (GH) secretion and inhibition of somatomedin C and other growth
      factor effects on their target tissues. In virilizing adrenal tumors height is
      increased at diagnosis, but after surgical cure the final height is usually in
      the normal range. In congenital adrenal hyperplasia height is usually compromised
      by advanced skeletal maturation or by suppressed growth, particularly in the
      first years of life, due to excess glucocorticoid treatment. The final height is
      reduced in both clinical forms (salt wasting and simple virilizing) and sexes in
      patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
      Growth impairment is also the hallmark of Cushing syndrome of whatever etiology
      when it occurs in children and growing adolescents, and the final height of these
      patients, even after surgical cure, remains compromised. This is apparently due
      to direct or indirect growth impairment by the hypercortisolism during the
      disease, followed by inadequate catch-up growth. Although it seems that GH
      treatment might be beneficial for improving final height both in patients with
      congenital adrenal hyperplasia who have poor height predictions and in patients
      with Cushing disease and GH deficiency, a larger number of studies is needed to
      confirm this suggestion.

PMID- 16444180
TI  - Effect of growth hormone (GH) on the immune system.
AB  - A growing body of evidence indicates a bi-directional relationship between the
      neuroendocrine system and immune functions. It is well known that lymphoid organs
      such the thymus, the spleen and peripheral blood produce growth hormone (GH) and
      GH receptor is expressed on different subpopulations of lymphocytes. Many in
      vitro and in animal studies demonstrate an important role of GH in
      immunoregulation. GH stimulates T and B cells proliferation and immunoglobulin
      synthesis, enhances the maturation of myeloid progenitor cells and is also able
      to modulate cytokine response. However, in humans GH deficiency (GHD) is not
      usually associated with immunodeficiency and only minor abnormalities of immune
      function have been reported, as compared to those observed in GHD animals. It is
      possible that in humans the GH produced locally in the immune system compensates
      for the lack of endocrine GH. In this review the main actions of GH on the immune
      system in vitro, in animal models and in humans are summarized.

PMID- 16444181
TI  - Acromegaly - evolving strategies.
AB  - Growth hormone (GH)-cell adenomas are benign pituitary tumors which present with
      chronic high GH output. Hereditary GH-cell adenomas are rare and include MEN I,
      McCune Albright Syndrome, Carney complex and familial acromegaly. Most of the
      tumors causing acromegaly are sporadic. Acromegaly is a disfiguring and disabling
      disease and, if untreated, life expectancy is reduced by a decade. Elevated GH
      levels, hypertension and heart disease are major negative survival determinants
      in these patients. Current treatments for acromegaly attempt to control the
      disease by reducing growth hormone secretion from the tumor either by surgery,
      radiotherapy or medical therapy. The choice of therapy depends on age, general
      health, the severity and complications of the disease and dangers associated with
      each treatment. Assessment of disease activity in patients with acromegaly
      following treatment is a problem because no sensitive clinical parameters are
      available and there is no well-defined clinical endpoint that defines cure. Cure
      in acromegaly has been defined therefore as normalization of biochemical
      parameters. A consensus publication recommended biochemical cure be considered as
      nadir GH of less than 1 microm g/L after OGTT and a normal circulating IGF-I. In
      optimizing the control of acromegaly new therapeutic strategies are evolving
      (growth hormone receptor antagonist - pegvisomant, potent dopamine agonists,
      universal somatostatin receptor ligands, chimeric molecules). The aim of the
      evolving therapeutic strategies is to produce a normal life expectancy in
      patients with acromegaly.

PMID- 16444182
TI  - Consequences of an intracranial germ cell-tumor in a young adolescent.
AB  - Germ cell tumors (GCTs) are relatively rare tumors, which arise in patients of
      all ages. They are most common in the first and second decades of life with a
      male predominance. The most frequent tumors arise in the pineal and suprasellar
      region. The long-term consequences of these tumors have not been very well
      characterized, as few series with a limited number of patients have reported on
      the neuro-endocrine development and quality of life of these young people. In
      this communication we present a male patient who was diagnosed clinically in 1998
      at the age of 17 years to have a GCT and subsequently treated with radiotherapy.
      Today, 6 years after the initial diagnosis his neuro-endocrine and neuro
      cognitive outcomes are quite good, while his quality of life is poor mainly due
      to many psychological problems that he experiences in his every day life.
      However, it has to be noted that 6 years is insufficient follow-up to assess late
      post radiation effects.

PMID- 16444183
TI  - Multiple pituitary hormone deficiency (MPHD) associated with normal height,
      absent puberty and obesity.
AB  - We present a 22-year old girl with MPHD and a normal pituitary imaging (MRI) who
      grew to normal size without GH. She was very obese. At age 19 years replacement
      therapy with hydrocortisone, L-thyroxine and sex steroids was started. Despite
      severe growth hormone deficiency according to the provocative tests and decreased
      IGF I level our patient grew normally. On follow up at age 22 she is 174cm tall.

PMID- 16444184
TI  - Differentiated thyroid carcinoma in children and adolescents: clinical course and
      therapeutic approach.
AB  - Thyroid carcinoma is an uncommon malignancy in the first two decades of life. It
      presents as a solitary thyroid nodule, multinodular goiter or as a long standing
      painless neck mass or both. Pediatric patients with thyroid carcinoma tend to
      present with more advanced disease than adults and have higher recurrence rates.
      The majority of all thyroid carcinomas in children and adolescents are of the
      papillary type. Surgery is the initial treatment, but the optimal surgical
      management is controversial. Ablation therapy with radioactive iodine, in order
      to destroy any thyroid remnant, and thyroxin therapy follow surgery. The
      prognosis even in cases with distant metastases is relatively good. Follow up
      should be performed at regular intervals and includes clinical examination,
      measurement of serum thyroglobulin levels, whole body scintigraphy and neck
      ultrasonography. As follow up is life long the care of these patients should be
      passed on to an adult endocrinologist. The consequences in adult patients with a
      history of childhood thyroid carcinoma should be evaluated.

PMID- 16444185
TI  - Thyroid associated ophthalmopathy: pediatric and endocrine aspects.
AB  - Childhood Graves' ophthalmopathy (GO) is a rare event: incidence rates (cases per
      100,000 population per year) are in the age groups 5-9, 10-14 and 15-19 years for
      females 3.5, 1.8 and 3.3 respectively, and for males 0, 1.7 and 0. The severity
      of childhood GO appears to be less than that of adulthood GO, presumably
      explained by the lower prevalence of smoking in children. IGF-I stimulates
      collagen synthesis and glucosaminoglycan production by orbital fibroblasts. Serum
      concentrations of free and total IGF-I and IGF-2 and of the three IGF-binding
      proteins in GO patients are similar to those of the controls. Increased IGF
      levels in retrobulbar tissues may thus represent autocrine or paracrine activity
      in theory susceptible to reduction by somatostatin analogues. Whereas orbital
      octreoscans are useful in the assesment of disease activity of GO, the efficacy
      of somatostatin analogues in the treatment of GO is rather modest - possibly
      related to their almost absent affinity for sst 1 and sst 4 receptors. The new
      compound SOM 230 might be much more effective in this respect.

PMID- 16444186
TI  - Somatostatin in diabetic retinopathy.
AB  - Diabetic retinopathy is a leading cause of legal blindness in the adult
      population (30-70 year olds). The anatomical changes that occur in the retina
      during the course of disease are well defined in the literature but the causes
      are not yet fully understood. Laser photocoagulation of the retina and vitrectomy
      are currently used to treat diabetic retinopathy but the procedures are invasive
      and provide only temporary protection. The use of long-acting analogues of the
      naturally occurring peptide, somatostatin, has been considered by some a
      promising therapeutic option for retinopathy over the last decade. Experimental
      evidence supports its use in diabetic retinopathy but further clinical evidence,
      from larger treatment groups of longer trial duration, is required. Improved
      analogues with increased selectivity and modified bi-specific analogues are
      currently emerging and may help to make the use of somatostatin analogues a more
      realistic option in the treatment of diabetic retinopathy.

PMID- 16444187
TI  - The role of growth hormone in the pathogenesis of diabetic kidney disease.
AB  - At present, diabetic kidney disease affects about 15-20% of all Type 1 diabetic
      patients and 20-40% of all patients with Type 2 diabetes. Preclinical research
      performed over the past decade has suggested growth hormone (GH) and insulin-like
      growth factors (IGFs) to be involved in the pathogenesis of diabetic kidney
      disease. Data obtained in knock-out (KO) mice with GH receptor (GHR)/GH binding
      protein (GHBP) gene-disruption have shown that these animals are protected
      against diabetes-induced renal changes. Further, diabetic mice treated with
      either a longacting somatostatin analogue or a specific GHR antagonist (GHRA)
      showed normalization of the diabetes-associated renal hypertrophy and glomerular
      enlargement and most importantly also a lowering effect on the diabetes-induced
      rise in urinary albumin excretion (UAE), a marker of renal damage. Based on these
      experimental data future studies are warranted to characterize the clinical
      potential of GH-inhibitors (e.g. GHRAs) as drugs for the treatment of diabetic
      renal complications.

PMID- 16444188
TI  - Hypoglycemia in childhood: long-term effects.
AB  - Glucose is the main cerebral fuel throughout life. Inadequate cerebral glucose
      supply, due to recurrent episodes of severe hypoglycemia during the neonatal
      period or infancy, when the brain is still developing, lead to serious long-term
      neurological impairments, ranging from mild neurocognitive dysfunction to severe
      mental retardation, epilepsy, microcephaly or even hemiparesis or aphasia.
      Moreover, in the most common form of severe recurrent hypoglycemia of infancy due
      to hyperinsulinism, not only abnormalities in neurocognitive function, but also
      the later development of diabetes mellitus are observed. Furthermore, recurrent
      hypoglycemia, supervening as a side-effect of intensified insulin treatment in
      young diabetic children, may also induce mild neurocognitive dysfunction and,
      specifically, memory deficits that predispose these children to new hypoglycemic
      episodes and hypoglycemia unawareness. In conclusion, prompt and meticulous
      management of hypoglycemia and its prevention during the neonatal period, infancy
      and childhood constitute the main goal of physicians taking care of these
      patients in order to ascertain a long-standing quality of life devoid of long
      term sequelae.

PMID- 16444189
TI  - The use of continuous subcutaneous insulin infusion (CSII) as the treatment of
      choice in children and adolescents with type 1 diabetes.
AB  - Continuous subcutaneous insulin infusion (CSII) by external pumps is shown in
      several clinical trials to be a safe and effective treatment modality for
      patients with T1D. The present prospective observational study evaluated the
      efficacy and safety of CSII in children and adolescents treated in a routine
      clinical setting. 186 patients using CSII from 3 to 30 months were included in
      the analysis. A significant decrease of GlyHbA1c was observed after 3 months (p <
      0.005) and was sustained throughout the study with a mean all over reduction of
      0.7%. Events of ketoacidosis and severe hypoglycemia amounted to 0.027 and 0.014
      per patient-year, respectively. Routine use of CSII in children and adolescents
      with T1D is effective in improving metabolic control and associated with a very
      low incidence of ketoacidosis or severe hypoglycemia.

PMID- 16444190
TI  - Genetic variation and health; towards individualized medicine.
AB  - BACKGROUND: Pediatric endocrine diseases and their adult consequences depend on
      interactions of environmental exposure factors with the genetic makeup of the
      individual. Much has been learned over the past two decades about the genetic
      component in cases of monogenic (Mendelian) disorders due to drastic disruption
      of a single gene. The majority of children consulting a pediatric
      endocrinologist, however, suffer from conditions not attributable to a single
      gene. The nature and mechanisms of more subtle alterations at multiple different
      genes that are responsible for the genetic component of most human morbidity and
      mortality is now only beginning to be elucidated, largely thanks to the vast
      amount of information that is becoming available through the human genome effort.
      OVERVIEW: The purpose of this review is to describe 1. the nature of the
      information on health-related human variation that is coming our of the genome
      effort; 2. how this variation can affect biology; 3. which research approaches
      show promise in linking DNA variation to disease; 4. how this variation is
      organized in genomic blocks of linkage disequilibrium; and 5. how this knowledge
      may, in the future, allow clinicians to individualize management of a specific
      patient according to his/her genetic makeup.

PMID- 16444191
TI  - Histopathological criteria for additional treatment after endoscopic mucosal
      resection for esophageal cancer: analysis of 464 surgically resected cases.
AB  - No previous reports on lymph-node metastasis (LNM) from superficial squamous cell
      carcinoma of the esophagus have proposed definite criteria for additional
      treatment after endoscopic mucosal resection (EMR). We investigated the
      association between histopathological factors and LNM in 464 consecutive patients
      with superficial squamous cell carcinoma of the esophagus who had undergone a
      radical esophagectomy with lymph-node dissection (14 'M1' lesions:
      intraepithelial tumors, 36 'M2' lesions: tumors invading the lamina propria, 50
      'M3' lesions: tumors in contact with or invading the muscularis mucosa, 32 'SM1'
      lesions: tumors invading the most superficial 1/3 of the submucosa and 332
      'SM2/3' lesions: tumors invading deeper than SM1 level). Histopathological
      factors including invasion depth, size, lymphatic invasion (LY), venous invasion,
      tumor differentiation, growth pattern, degree of nuclear atypia and histological
      grade were assessed for their association with LNM in 82 M3 or SM1 lesions to
      determine which patients need additional treatment after EMR. LNM was found in
      0.0, 5.6, 18.0, 53.1 and 53.9% of the M1, M2, M3, SM1 and SM2/3 lesions,
      respectively. A univariate analysis showed that each of the following
      histopathological factors had a significant influence on LNM: invasion depth (M3
      vs SM1), LY, venous invasion and histological grade. Invasion depth and LY were
      significantly associated with LNM in a multivariate analysis. Four out of 38
      patients (10.3%) with M3 lesions without LY had LNM, whereas five out of 12
      patients (41.7%) with M3 lesions and LY had LNM. Only patients with M1/2 lesions
      are good candidates for EMR. Invading the muscularis mucosa (M3) is a high-risk
      condition for LNM the same as submucosal invasion, but M3 lesions without LY can
      be followed up after EMR without any additional treatment.

PMID- 16444192
TI  - Atypical reactive proliferation of endocervix: a common lesion associated with
      endometrial carcinoma and likely related to prior endometrial sampling.
AB  - We describe a common, but hitherto not well described, reactive change of the
      endocervical surface epithelium, commonly seen in association with endometrial
      carcinoma, and which we term 'atypical reactive proliferation'. This lesion,
      especially when florid, has the potential to be misinterpreted as a manifestation
      of a stage 2A endometrial cancer (endocervical glandular involvement). We
      examined the cervical sections in 80 consecutive hysterectomy specimens of
      endometrial cancer. In 22 cases (27.5%), there was cervical involvement by tumour
      and these cases were excluded from further analysis. Of the remaining cases,
      atypical reactive proliferation involved the endocervical surface in 40 of 58
      (69%) cases, although the degree of abnormality varied widely between individual
      cases. Histological features characteristic of atypical reactive proliferation
      (not all features were present in each case) included nuclear stratification and
      multilayering with short micropapillary processes, squamoid change, hobnail cells
      and mild cytological atypia. Other features present in some cases were surface
      erosion, clearing of the cytoplasm, fibrin deposition, an inflammatory cell
      infiltrate and fibrosis of the subepithelial tissue. In 20 control cases,
      comprising hysterectomy specimens for benign conditions, similar changes were not
      seen. Vimentin immunohistochemistry was undertaken in eight cases in which
      atypical reactive proliferation was particularly florid. Five cases were
      completely negative and three exhibited very focal positivity. Atypical reactive
      proliferation involving the endocervical surface is commonly seen in association
      with endometrial cancer and has the potential to be misinterpreted as
      endocervical involvement by tumour. Although this could represent a reactive
      change associated with the presence of an endometrial cancer, we feel atypical
      reactive proliferation is most likely a reactive/reparative response to recent
      endometrial biopsy or curettage. The vimentin-negative immunophenotype may be of
      value in cases where the uterine carcinoma is endometrioid in type as these
      neoplasms are generally vimentin positive.

PMID- 16444193
TI  - Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ
      hybridization in the HER2 testing algorithm.
AB  - Assessment of human epidermal growth factor receptor-2 status is standard
      practice in women with breast cancer. Most laboratories use immunohistochemistry
      as a screening test, with equivocal results confirmed by fluorescence in-situ
      hybridization (FISH). Chromogenic in-situ hybridization (CISH) is a relatively
      new method for detection of gene amplification using a peroxidase reaction, which
      can be viewed using a standard light microscope. This study was undertaken to
      validate CISH as a method for assessing human epidermal growth factor receptor-2
      gene amplification. The gene amplification status of human epidermal growth
      factor receptor-2 immunohistochemistry negative (0/1+, n = 69; Group 1),
      immunohistochemistry positive (3+, n = 50; Group 2) and equivocal tumor samples
      (2+, n = 135; Group 3) was evaluated by FISH and CISH, and the concordance
      between FISH and CISH results calculated. In Group 1, 67/69 cases did not show
      amplification by CISH and 69/69 showed no amplification by FISH. Two cases were
      discordant; therefore, fluorescence/CISH concordance was 97%. In Group 2, 46/50
      cases were amplified by FISH and 47/50 cases were amplified by CISH; three cases
      were not amplified by either method (immunohistochemistry false-positives). Only
      one case showed discordant FISH and CISH results, making the fluorescence/CISH
      concordance 98%. In Group 3, 89/135 cases were not amplified and 37/135 were
      amplified by both methods. Nine cases were discordant, giving a fluorescence/CISH
      concordance of 93%. The discordant cases were those with very low or borderline
      amplification with FISH. The high level of concordance between FISH and CISH seen
      in this study suggests that CISH may be a viable alternative to FISH for use in
      the human epidermal growth factor receptor-2 testing algorithm.

PMID- 16444195
TI  - Special care dentistry.

PMID- 16444194
TI  - AIDS and non-AIDS diffuse large B-cell lymphomas express different antigen
      profiles.
AB  - Based on gene expression profiling, diffuse large B-cell lymphomas arising in
      immunocompetent patients can be divided into germinal center and activated B-cell
      types. Since little is known about acquired immunodeficiency syndrome associated
      diffuse large B-cell lymphomas, we tested whether the protein expression of
      germinal center and activated B-cell markers differed between acquired
      immunodeficiency syndrome (AIDS) vs non-AIDS diffuse large B-cell lymphomas. We
      immunohistochemically stained tissue microarrays of 39 de novo diffuse large B
      cell lymphomas: 12 AIDS associated and 27 non-AIDS, with germinal center (BCL6,
      CD10, CyclinH) and activated B-cell markers (MUM1, CD138, PAK1, CD44, BCL2). We
      scored each case for percent positive cells (0-19%=0; 20-49%=1; 50-100%=2). The
      activated B-cell and germinal center summation scores of each case were used as
      (x, y) coordinate data points to construct two-dimensional contour-frequency
      plots. The contour plot of non-AIDS diffuse large B-cell lymphomas showed two
      distinct clusters: a cluster with a high germinal center phenotype (cluster 1)
      and a cluster with a high activated B-cell phenotype (cluster 3). In contrast,
      the AIDS-related diffuse large B-cell lymphomas formed a single aggregate
      (cluster 2) (P=0.02, Fisher exact test). When the contour plots of the AIDS
      related and the non-AIDS cases were superimposed, cluster 2 of the AIDS cases
      expressed an intermediate germinal center/activated B-cell phenotype compared to
      clusters 1 and 3 of the non-AIDS diffuse large B-cell lymphomas. Our results
      confirm that non-AIDS diffuse large B-cell lymphomas segregate into two groups
      with either germinal center or activated B-cell phenotype. We report the new
      finding that the AIDS status of the patient predicts the immunophenotype of the
      diffuse large B-cell lymphomas.

PMID- 16444196
TI  - Check your UDAs.

PMID- 16444197
TI  - Ozone slayers.

PMID- 16444199
TI  - Da iawn!

PMID- 16444200
TI  - A catalyst for change.

PMID- 16444201
TI  - Difficulty with samples.

PMID- 16444202
TI  - Formation of salts.

PMID- 16444203
TI  - Oral insecticidation.

PMID- 16444204
TI  - An epistemological approach.

PMID- 16444205
TI  - Protecting staff and patients.

PMID- 16444206
TI  - Brainstorming.

PMID- 16444207
TI  - Nicotine, smoke and patches.

PMID- 16444221
TI  - Academic dentistry--where is everybody?
AB  - If someone had told us, when we were undergraduates, that there was a career
      which allowed you the time, and gave you the support, to pursue and research the
      things about your profession which most interested you, we would have been
      intrigued. If we had then been informed that there was paid employment which
      encouraged you to travel extensively abroad, talking about your work, and also
      gave you the brightest young minds in the country to engage with, teach and learn
      from, we would have thought this job sounded very tempting. If we had then been
      told that it also provided secretaries and administrators to help you do your
      job, and was carried out in a non-hierarchical, collegiate environment where
      equality and diversity are valued--we would have jumped at the chance! And did!
      Because what is described above is the life of a clinical academic. Although all
      the above are part of the role of the academic, there is also immense value and
      joy to be obtained through scholarship, education and teaching, which are
      sometimes forgotten because so much of our time and energy is directed to dealing
      with our patients' problems, while wrestling with the intricacies of new
      contracts, clinical governance, evidence based practice, and so forth.

PMID- 16444222
TI  - Oral medicine--update for the dental practitioner orofacial pain.
AB  - This series provides an overview of current thinking in the more relevant areas
      of oral medicine for primary care practitioners, written by the authors while
      they were holding the Presidencies of the European Association for Oral Medicine
      and the British Society for Oral Medicine, respectively. A book containing
      additional material will be published. The series gives the detail necessary to
      assist the primary dental clinical team caring for patients with oral complaints
      that may be seen in general dental practice. Space precludes inclusion of
      illustrations of uncommon or rare disorders, or discussion of disorders affecting
      the hard tissues. Approaching the subject mainly by the symptomatic approach--as
      it largely relates to the presenting complaint--was considered to be a more
      helpful approach for GDPs rather than taking a diagnostic category approach. The
      clinical aspects of the relevant disorders are discussed, including a brief
      overview of the aetiology, detail on the clinical features and how the diagnosis
      is made. Guidance on management and when to refer is also provided, along with
      relevant websites which offer further detail.

PMID- 16444223
TI  - Tobacco cessation activities of UK dentists in primary care: signs of
      improvement.
AB  - OBJECTIVE: To investigate attitudes and opinions of the members of the British
      Dental Association towards implementing tobacco cessation strategies in dental
      practices. DESIGN AND METHOD: Questions about tobacco and tobacco cessation were
      asked on the September 2002 BDA Omnibus survey. The survey was sent out to a
      random sample of 1,500 BDA members, excluding retired members, overseas members
      and students. After two reminder circulations, 870 completed questionnaires were
      received, giving a response rate of 58%. RESULTS: The survey results revealed
      good awareness amongst respondents of the health risks of tobacco. One fifth of
      respondents said that patients had asked them for advice on tobacco cessation.
      The majority (64%) of respondents stated that they gave advice on tobacco
      cessation 'fairly regularly' or 'always' (whether asked or not) and 37% of
      respondents recommended over-the-counter nicotine replacement therapy. Overall,
      68% of respondents agreed that offering patients advice about tobacco cessation
      was the duty of every dentist. The most common barriers to a successful tobacco
      cessation campaign were perceived to be the amount of time required, lack of
      reimbursement, lack of training, lack of patient education materials and lack of
      knowledge of available referral resources. Nearly all respondents (92%) said that
      their practice was a completely smoke-free environment, and 66% of respondents
      had never used tobacco. The majority of respondents displayed patient education
      materials in their practice waiting/reception areas less than 60% of the time,
      and nearly a quarter (23%) never had them available. The survey revealed that
      most respondents did not feel particularly well prepared to assist patients in
      quitting tobacco, but 70% of respondents said they would be willing to cooperate
      with a campaign to inform all tobacco using patients about the advantages of
      tobacco cessation. Respondents felt that leaflets for patients, staff training
      and posters in the practice would contribute to the success of the campaign.
      CONCLUSION: Members of the dental team are very willing to implement tobacco
      cessation strategies in the dental practice. Most dentists feel that promotion of
      tobacco cessation is an important part of the duty of a dentist, but they feel
      inadequately prepared to deliver such advice. The major barriers to delivering
      successful tobacco cessation campaigns are the amount of time required, lack of
      reimbursement, lack of training, lack of patient education materials and lack of
      knowledge of available referral resources. The majority of dentists have received
      no training in tobacco cessation strategies. They feel that staff training and
      free availability of more patient education materials (leaflets, posters, etc)
      would help promote the success of such a campaign.

PMID- 16444230
TI  - Patients' and sleeping partners' experience of treatment for sleep-related
      breathing disorders with a mandibular repositioning splint.
AB  - AIM: To determine in detail the complications associated with the use of
      mandibular repositioning splints (MRS) to treat sleep-related breathing
      disorders. METHOD: This prospective cross-sectional cohort study audits the
      management with mandibular repositioning splints of 121 patients suffering from
      sleep-related breathing disorders. Investigation of patients' and sleeping
      partners' perspectives on treatment was undertaken with the use of a
      questionnaire based study. RESULTS: Sixty-eight per cent of respondents reported
      that they were compliant with treatment; various side effects were reported of
      which excess salivation was the most common. Investigation of sleeping partners'
      perspectives revealed that 70% felt that their partners' snoring was improved and
      47% felt that their partner's breathing pauses during sleep were reduced. Sixty
      four per cent of the sleeping partners also reported that their own sleep pattern
      had improved since their partner's treatment. CONCLUSION: Mandibular
      repositioning splints used in the manner described by this paper are demonstrated
      to have a good compliance rate, provide successful treatment and exhibit only
      minor, reversible side effects.

PMID- 16444231
TI  - An investigation into the practice of tongue piercing in the South West of
      England.
AB  - OBJECTIVE: To investigate the prevalence and range of complications following
      tongue piercing. METHODS: A survey of individuals with tongue piercings
      ('piercees') and tongue piercers was undertaken in the South West of England. One
      hundred and twenty-three piercees completed a self-administered questionnaire and
      22 piercers took part in an interviewer-led questionnaire. RESULTS: The mean age
      of an individual having a tongue piercing was 19 years old. Almost all the
      subjects reported problems following piercing; early problems were mainly due to
      tissue trauma, whereas later, ingestion of jewellery and tooth fracture were
      common events. A minority (7%) of piercees required the advice of a healthcare
      professional following tongue piercing. The majority of piercers reported
      adequate cross-infection measures and enquired about their clients' health prior
      to piercing. However, only one piercer was aware of the risk of bacterial
      endocarditis following tongue piercing. Most of the piercers reported that they
      would advise their clients to attend an Accident and Emergency department if a
      serious complication ensued. CONCLUSION: Tongue piercing may be associated with
      significant short-term and long-term morbidity, including tooth damage. Although
      the majority of piercers interviewed reported adequate cross-infection controls,
      knowledge of the medical risks associated with tongue piercing varied widely.

PMID- 16444246
TI  - Organ, organelle, organism.

PMID- 16444243
TI  - Relief after the wave.

PMID- 16444248
TI  - Ciliary proteins and exencephaly.

PMID- 16444249
TI  - Anthrax target in macrophages unveiled.

PMID- 16444250
TI  - Defense and counterdefense in the plant world.

PMID- 16444251
TI  - Expressing physiology.

PMID- 16444252
TI  - The rise and fall of the ape Y chromosome?

PMID- 16444255
TI  - Evidence for an instructive mechanism of de novo methylation in cancer cells.
AB  - DNA methylation has a role in the regulation of gene expression during normal
      mammalian development but can also mediate epigenetic silencing of CpG island
      genes in cancer and other diseases. Many individual genes (including tumor
      suppressors) have been shown to undergo de novo methylation in specific tumor
      types, but the biological logic inherent in this process is not understood. To
      decipher this mechanism, we have adopted a new approach for detecting CpG island
      DNA methylation that can be used together with microarray technology. Genome-wide
      analysis by this technique demonstrated that tumor-specific methylated genes
      belong to distinct functional categories, have common sequence motifs in their
      promoters and are found in clusters on chromosomes. In addition, many are already
      repressed in normal cells. These results are consistent with the hypothesis that
      cancer-related de novo methylation may come about through an instructive
      mechanism.

PMID- 16444257
TI  - Langerhans cells arise from monocytes in vivo.
AB  - Langerhans cells (LCs) are the only dendritic cells of the epidermis and
      constitute the first immunological barrier against pathogens and environmental
      insults. The factors regulating LC homeostasis remain elusive and the direct
      circulating LC precursor has not yet been identified in vivo. Here we report an
      absence of LCs in mice deficient in the receptor for colony-stimulating factor 1
      (CSF-1) in steady-state conditions. Using bone marrow chimeric mice, we have
      established that CSF-1 receptor-deficient hematopoietic precursors failed to
      reconstitute the LC pool in inflamed skin. Furthermore, monocytes with high
      expression of the monocyte marker Gr-1 (also called Ly-6c/G) were specifically
      recruited to the inflamed skin, proliferated locally and differentiated into LCs.
      These results identify Gr-1(hi) monocytes as the direct precursors for LCs in
      vivo and establish the importance of the CSF-1 receptor in this process.

PMID- 16444258
TI  - Particularities of the vasculature can promote the organ specificity of
      autoimmune attack.
AB  - How certain autoimmune diseases target specific organs remains obscure. In the
      'K/BxN' arthritis model, autoantibodies to a ubiquitous antigen elicit joint
      restricted pathology. Here we have used intravital imaging to demonstrate that
      transfer of arthritogenic antibodies caused macromolecular vasopermeability
      localized to sites destined to develop arthritis, augmenting its severity.
      Vasopermeability depended on mast cells, neutrophils and FcgammaRIII but not
      complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant
      FcRgamma-expressing cells in an organ distant from the joint were required.
      Histamine and serotonin were critical, and systemic administration of these
      vasoactive amines recapitulated the joint localization of immune complex
      triggered vasopermeability. We propose that regionally distinct vascular
      properties 'interface' with immune effector pathways to foster organ-specific
      autoimmune damage, perhaps explaining why arthritis accompanies many human
      infectious and autoimmune disorders.

PMID- 16444259
TI  - The Birc1e cytosolic pattern-recognition receptor contributes to the detection
      and control of Legionella pneumophila infection.
AB  - Baculovirus inhibitor of apoptosis repeat-containing 1 (Birc1) proteins have
      homology to several germline-encoded receptors of the innate immune system.
      However, their function in immune surveillance is not clear. Here we describe a
      Birc1e-dependent signaling pathway that restricted replication of the
      intracellular pathogen Legionella pneumophila in mouse macrophages. Translocation
      of bacterial products into host-cell cytosol was essential for Birc1e-mediated
      control of bacterial replication. Caspase-1 was required for Birc1e-dependent
      antibacterial responses ex vivo in macrophages and in a mouse model of
      Legionnaires' disease. The interleukin 1beta converting enzyme-protease
      activating factor was necessary for L. pneumophila growth restriction, but
      interleukin 1beta was not required. These results establish Birc1e as a
      nucleotide-binding oligomerization-leucine-rich repeat protein involved in the
      detection and control of intracellular L. pneumophila.

PMID- 16444260
TI  - T cells use two directionally distinct pathways for cytokine secretion.
AB  - Activated T helper cells produce many cytokines, some of which are secreted
      through the immunological synapse toward the antigen-presenting cell. Here we
      have used immunocytochemistry, live-cell imaging and a surface-mediated secretion
      assay to show that there are two cytokine export pathways in T helper cells. Some
      cytokines, including interleukin 2 and interferon-gamma, were secreted into the
      synapse, whereas others, including tumor necrosis factor and the chemokine CCL3
      (MIP-1alpha), were released multidirectionally. Each secretion pathway was
      associated with different trafficking proteins, indicating that they are
      molecularly distinct processes. These data suggest that T helper cells release
      some cytokines into the immunological synapse to impart specific communication
      and others multidirectionally to promote inflammation and to establish chemokine
      gradients.

PMID- 16444261
TI  - Tuning the erosion rate of artificial protein hydrogels through control of
      network topology.
AB  - Erosion behaviour governs the use of physical hydrogels in biomedical
      applications ranging from controlled release to cell encapsulation. Genetically
      engineered protein hydrogels offer unique means of controlling the erosion rate
      by engineering their amino acid sequences and network topology. Here, we show
      that the erosion rate of such materials can be tuned by harnessing selective
      molecular recognition, discrete aggregation number and orientational
      discrimination of coiled-coil protein domains. Hydrogels formed from a triblock
      artificial protein bearing dissimilar helical coiled-coil end domains (P and A)
      erode more than one hundredfold slower than hydrogels formed from those bearing
      the same end domains (either P or A). The reduced erosion rate is a consequence
      of the fact that looped chains are suppressed because P and A tend not to
      associate with each other. Thus, the erosion rate can be tuned over several
      orders of magnitude in artificial protein hydrogels, opening the door to diverse
      biomedical applications.

PMID- 16444263
TI  - Hierarchically structured transparent hybrid membranes by in situ growth of
      mesostructured organosilica in host polymer.
AB  - The elaborate performances characterizing natural materials result from
      functional hierarchical constructions at scales ranging from nanometres to
      millimetres, each construction allowing the material to fit the physical or
      chemical demands occurring at these different levels. Hierarchically structured
      materials start to demonstrate a high input in numerous promising applied domains
      such as sensors, catalysis, optics, fuel cells, smart biologic and cosmetic
      vectors. In particular, hierarchical hybrid materials permit the accommodation of
      a maximum of elementary functions in a small volume, thereby optimizing
      complementary possibilities and properties between inorganic and organic
      components. The reported strategies combine sol-gel chemistry, self-assembly
      routes using templates that tune the material's architecture and texture with the
      use of larger inorganic, organic or biological templates such as latex,
      organogelator-derived fibres, nanolithographic techniques or controlled phase
      separation. We propose an approach to forming transparent hierarchical hybrid
      functionalized membranes using in situ generation of mesostructured hybrid phases
      inside a non-porogenic hydrophobic polymeric host matrix. We demonstrate that the
      control of the multiple affinities existing between organic and inorganic
      components allows us to design the length-scale partitioning of hybrid
      nanomaterials with tuned functionalities and desirable size organization from
      angstrom to centimetre. After functionalization of the mesoporous hybrid silica
      component, the resulting membranes have good ionic conductivity offering
      interesting perspectives for the design of solid electrolytes, fuel cells and
      other ion-transport microdevices.

PMID- 16444262
TI  - An X-ray computed tomography imaging agent based on long-circulating bismuth
      sulphide nanoparticles.
AB  - Nanomaterials have become increasingly important in the development of new
      molecular probes for in vivo imaging, both experimentally and clinically.
      Nanoparticulate imaging probes have included semiconductor quantum dots, magnetic
      and magnetofluorescent nanoparticles, gold nanoparticles and nanoshells, among
      others. However, the use of nanomaterials for one of the most common imaging
      techniques, computed tomography (CT), has remained unexplored. Current CT
      contrast agents are based on small iodinated molecules. They are effective in
      absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have
      rather limited their microvascular and targeting performance. Here we propose the
      use of a polymer-coated Bi(2)S(3) nanoparticle preparation as an injectable CT
      imaging agent. This preparation demonstrates excellent stability at high
      concentrations (0.25 M Bi(3+)), high X-ray absorption (fivefold better than
      iodine), very long circulation times (>2 h) in vivo and an efficacy/safety
      profile comparable to or better than iodinated imaging agents. We show the
      utility of these polymer-coated Bi(2)S(3) nanoparticles for enhanced in vivo
      imaging of the vasculature, the liver and lymph nodes in mice. These
      nanoparticles and their bioconjugates are expected to become an important adjunct
      to in vivo imaging of molecular targets and pathological conditions.

PMID- 16444264
TI  - Autoimmunity and tumor immunity induced by immune responses to mutations in self.
AB  - Little is known about the consequences of immune recognition of mutated gene
      products, despite their potential relevance to autoimmunity and tumor immunity.
      To identify mutations that induce immunity, here we have developed a systematic
      approach in which combinatorial DNA libraries encoding large numbers of random
      mutations in two syngeneic tyrosinase-related proteins are used to immunize black
      mice. We show that the libraries of mutated DNA induce autoimmune
      hypopigmentation and tumor immunity through cross-recognition of nonmutated gene
      products. Truncations are present in all immunogenic clones and are sufficient to
      elicit immunity to self, triggering recognition of normally silent epitopes.
      Immunity is further enhanced by specific amino acid substitutions that promote T
      helper cell responses. Thus, presentation of a vast repertoire of antigen
      variants to the immune system can enhance the generation of adaptive immune
      responses to self.

PMID- 16444265
TI  - A novel dendritic cell subset involved in tumor immunosurveillance.
AB  - The interferon (IFN)-gamma-induced TRAIL effector mechanism is a vital component
      of cancer immunosurveillance by natural killer (NK) cells in mice. Here we show
      that the main source of IFN-gamma is not the conventional NK cell but a subset of
      B220(+)Ly6C(-) dendritic cells, which are atypical insofar as they express NK
      cell-surface molecules. Upon contact with a variety of tumor cells that are
      poorly recognized by NK cells, B220(+)NK1.1(+) dendritic cells secrete high
      levels of IFN-gamma and mediate TRAIL-dependent lysis of tumor cells. Adoptive
      transfer of these IFN-producing killer dendritic cells (IKDCs) into tumor-bearing
      Rag2(-/-)Il2rg(-/-) mice prevented tumor outgrowth, whereas transfer of
      conventional NK cells did not. In conclusion, we identified IKDCs as pivotal
      sensors and effectors of the innate antitumor immune response.

PMID- 16444266
TI  - Interferon-producing killer dendritic cells provide a link between innate and
      adaptive immunity.
AB  - Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central
      components of innate and adaptive immune responses. We describe here a third DC
      lineage, termed interferon-producing killer DCs (IKDCs), distinct from
      conventional DCs and plasmacytoid DCs and with the molecular expression profile
      of both NK cells and DCs. They produce substantial amounts of type I interferons
      (IFN) and interleukin (IL)-12 or IFN-gamma, depending on activation stimuli. Upon
      stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)
      9, IKDCs kill typical NK target cells using NK-activating receptors. Their
      cytolytic capacity subsequently diminishes, associated with the loss of NKG2D
      receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity
      is lost, DC-like antigen-presenting activity is gained, associated with
      upregulation of surface major histocompatibility complex class II (MHC II) and
      costimulatory molecules, which formally distinguish them from classical NK cells.
      In vivo, splenic IKDCs preferentially show NK function and, upon systemic
      infection, migrate to lymph nodes, where they primarily show antigen-presenting
      cell activity. By virtue of their capacity to kill target cells, followed by
      antigen presentation, IKDCs provide a link between innate and adaptive immunity.

PMID- 16444267
TI  - Systemic delivery of morpholino oligonucleotide restores dystrophin expression
      bodywide and improves dystrophic pathology.
AB  - For the majority of Duchenne muscular dystrophy (DMD) mutations, antisense
      oligonucleotide (AON)-mediated exon skipping has the potential to restore a
      functional protein. Here we show that weekly intravenous injections of morpholino
      phosphorodiamidate (morpholino) AONs induce expression of functional levels of
      dystrophin in body-wide skeletal muscles of the dystrophic mdx mouse, with
      resulting improvement in muscle function. Although the level of dystrophin
      expression achieved varies considerably between muscles, antisense therapy may
      provide a realistic hope for the treatment of a majority of individuals with DMD.

PMID- 16444268
TI  - Neurotrophins mediate human embryonic stem cell survival.
AB  - Growth of human embryonic stem (hES) cells as a pluripotent population requires a
      balance between survival, proliferation and self-renewal signals. Here we
      demonstrate that hES cells express receptors of the tropomyosin-related kinase
      (TRK) family, which mediate antiapoptotic signals. We show that three TRK
      ligands, brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4,
      are survival factors for hES cells. Addition of neurotrophins to hES cell
      cultures effects a 36-fold improvement in their clonal survival. hES cell
      cultures maintained in medium containing neurotrophins remain diploid and retain
      full developmental potency. In the presence of neurotrophins, TRK receptors in
      hES cells are phosphorylated; TRK receptor inhibition leads to hES cell
      apoptosis. The survival activity of neurotrophins in hES cells is mediated by the
      phosphatidylinositol-3-kinase pathway but not the mitogen-activated protein
      kinase pathway. Neurotrophins improve hES cell survival and may facilitate their
      manipulation and the development of high-throughput screens to identify factors
      responsible for hES cell differentiation.

PMID- 16444269
TI  - Identification and immunotherapeutic targeting of antigens induced by
      chemotherapy.
AB  - Cancer cells differ from normal cells in their response to chemotherapy. We
      exploited this dissimilarity by identifying and targeting tumor-specific, cell
      surface proteins whose expression is induced by the chemotherapeutic irinotecan
      (CPT-11; Camptosar). A cytotoxin-armed antibody reactive with one of these drug
      induced surface proteins, the LY6D/E48 antigen, originally identified as the
      target of a monoclonal antibody reactive with squamous cell carcinomas, caused
      complete regression of colorectal tumor xenografts in mice treated with CPT-11,
      whereas either agent alone was less effective. These results suggest that a
      positive therapeutic index may be generated for other drug combinations by
      immunotherapeutic targeting of chemotherapy-induced antigens.

PMID- 16444270
TI  - Variable channel expression in identified single and electrically coupled neurons
      in different animals.
AB  - It is often assumed that all neurons of the same cell type have identical
      intrinsic properties, both within an animal and between animals. We exploited the
      large size and small number of unambiguously identifiable neurons in the crab
      stomatogastric ganglion to test this assumption at the level of channel mRNA
      expression and membrane currents (measured in voltage-clamp experiments). In
      lateral pyloric (LP) neurons, we saw strong correlations between measured current
      and the abundance of Shal and BK-KCa mRNAs (encoding the Shal-family voltage
      gated potassium channel and large-conductance calcium-activated potassium
      channel, respectively). We also saw two- to fourfold interanimal variability for
      three potassium currents and their mRNA expression. Measurements of channel
      expression in the two electrically coupled pyloric dilator (PD) neurons showed
      significant interanimal variability, but copy numbers for IH (encoding the
      hyperpolarization-activated, inward-current channel) and Shal mRNA in the two PD
      neurons from the same crab were similar, suggesting that the regulation of some
      currents may be shared in electrically coupled neurons.

PMID- 16444271
TI  - Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis
      vulgaris.
AB  - Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of
      keratinization and one of the most frequent single-gene disorders in humans. The
      most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy
      English schoolchildren. We have identified homozygous or compound heterozygous
      mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of
      moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these
      mutations are semidominant; heterozygotes show a very mild phenotype with
      incomplete penetrance. The mutations show a combined allele frequency of
      approximately 4% in populations of European ancestry, explaining the high
      incidence of ichthyosis vulgaris. Profilaggrin is the major protein of
      keratohyalin granules in the epidermis. During terminal differentiation, it is
      cleaved into multiple filaggrin peptides that aggregate keratin filaments. The
      resultant matrix is cross-linked to form a major component of the cornified cell
      envelope. We find that loss or reduction of this major structural protein leads
      to varying degrees of impaired keratinization.

PMID- 16444272
TI  - Dominance relationships between self-incompatibility alleles controlled by DNA
      methylation.
AB  - In crucifers, the pollen S-determinant gene, SP11, is sporophytically expressed
      in the anther tapetum, and the pollen self-incompatibility phenotype is
      determined by the dominance relationships between the two S-haplotypes it
      carries. We report here that 5' promoter sequences of recessive SP11 alleles are
      specifically methylated in the tapetum before the initiation of SP11
      transcription. These results suggest that tissue-specific monoallelic de novo DNA
      methylation is involved in determining the dominance interactions that determine
      the cruciferous self-incompatibility phenotype.

PMID- 16444275
TI  - Allogeneic bone marrow transplantation in a child with severe aplastic anemia and
      hemophilia A.

PMID- 16444274
TI  - Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic
      aneurysm/aortic dissection and patent ductus arteriosus.
AB  - We have recently described two kindreds presenting thoracic aortic aneurysm
      and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the
      disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is
      caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region
      of the smooth muscle myosin heavy chain, a specific contractile protein of smooth
      muscle cells (SMC). All individuals bearing the heterozygous mutations, even if
      asymptomatic, showed marked aortic stiffness. Examination of pathological aortas
      showed large areas of medial degeneration with very low SMC content. Abnormal
      immunological recognition of SM-MHC and the colocalization of wild-type and
      mutant rod proteins in SMC, in conjunction with differences in their
      coimmunoprecipitation capacities, strongly suggest a dominant-negative effect.
      Human MYH11 gene mutations provide the first example of a direct change in a
      specific SMC protein leading to an inherited arterial disease.

PMID- 16444277
TI  - Adefovir therapy for lamivudine escape and hepatitis B virus reactivation after
      reduced intensity conditioning allogeneic stem cell transplantation.

PMID- 16444276
TI  - Conversion of the severe to the moderate disease phenotype with donor leukocyte
      microchimerism in canine leukocyte adhesion deficiency.
AB  - Leukocyte adhesion deficiency-1 (LAD-1), a genetic immunodeficiency disease
      characterized by life-threatening bacterial infections, results from the
      defective adherence and migration of leukocytes due to mutations in the leukocyte
      integrin CD18 molecule. Canine LAD (CLAD) represents the canine homologue of the
      severe phenotype of LAD-1 in children. In previous studies we demonstrated that
      non-myeloablative stem cell transplantation from matched littermates resulted in
      mixed donor-host chimerism and reversal of the disease phenotype in CLAD. In this
      study, we describe two CLAD dogs with less than 2% donor leukocyte chimerism
      following non-myeloablative transplant. Both dogs are alive more than 24 months
      after transplant with an attenuated CLAD phenotype resembling the moderate
      deficiency phenotype of LAD. The improvement in the CLAD phenotype with very low
      levels of donor CD18(+) leukocytes correlated with the preferential egress of the
      CD18(+) neutrophils into extravascular sites. The clinical response with very low
      levels of donor CD18(+) leukocytes in CLAD supports using this model for testing
      gene therapy strategies since the low levels of gene-corrected hematopoietic
      cells expected with hematopoietic gene therapy would likely have a therapeutic
      effect in CLAD.

PMID- 16444278
TI  - Urinary reactivation of polyoma BK virus but not adenovirus in paediatric and
      adolescent patients after haematopoietic stem cell transplantation.

PMID- 16444279
TI  - A comparison of an anti-CD25 immunotoxin, Ontak and anti-CD25 microbeads for
      their ability to deplete alloreactive T cells in vitro.
AB  - Ex vivo depletion of alloreactive CD25(+) T cells from a stem cell transplant
      (SCT) can reduce the incidence of graft-versus-host disease (GVHD) while
      preserving antimicrobial and perhaps antileukemia activity. However, the most
      effective methods for allodepleting T cells prior to transplant have not been
      determined. In this study, we have compared three agents that deplete CD25(+)
      activated, alloreactive T cells. These included Ontak (Denileukin Diftitox), an
      IL-2 fusion toxin, anti-CD25 microbeads (MACS), an anti-CD25 immunotoxin (IT) and
      a combination of the IT and MACS. Peripheral blood mononuclear cells (PBMCs)
      activated in a primary mixed lymphocyte reaction (MLR) were allodepleted using
      optimal amounts of each agent, and the cells were then analyzed by flow
      cytometry. The treated cells were examined both for remaining alloreactivity and
      for the preservation of third party reactivity by testing them in a secondary
      MLR. Our data demonstrate that both the anti-CD25 IT and the anti-CD25 MACS were
      equally effective in depleting CD4(+)CD25(+) cells and in sparing T cells that
      were reactive with third party cells. The anti-CD25 IT was, however, superior in
      depleting alloreactive CD8(+)CD25(+) cells. In contrast, Ontak did not eliminate
      alloreactive cells and the Ontak-treated cells retained significant reactivity
      against the original stimulator cells.

PMID- 16444280
TI  - Increased intensity of acute graft-versus-host disease after reduced-intensity
      bone marrow transplantation compared to conventional transplantation from an HLA
      matched sibling in children.
AB  - Eight children underwent reduced-intensity stem cell transplantation (RIST) from
      an HLA-matched sibling. They received a fludarabine-melphalan based preparative
      regimen. Stem cell source was bone marrow, and GVHD prophylaxis consisted of
      cyclosporine A alone. Acute GVHD grade II-IV and grade III-IV were observed in
      four (50%) and three (37.5%), respectively, out of these eight patients. This
      incidence was significantly higher than that after conventional bone marrow
      transplantation, without severe tissue damage, in the same setting of stem cell
      source and GVHD prophylaxis. Although the number of patients is small, our
      results suggest that incidence of acute GVHD after RIST for children is
      significant. It should be remembered that RIST for children does not seem to be
      an easy transplant procedure from the viewpoint of acute GVHD, although RIST is
      less toxic.

PMID- 16444281
TI  - Guillain-Barre syndrome associated with rapid immune reconstitution following
      allogeneic hematopoietic stem cell transplantation.

PMID- 16444282
TI  - Ideal rather than actual body weight should be used to calculate cell dose in
      allogeneic hematopoietic stem cell transplantation.
AB  - Whether the CD34+ and CD3+ cell doses in allogeneic HSCT should be estimated
      using actual (ABW) or ideal (IBW) body weight has never been definitively
      determined. We have shown that CD34+ cell doses based upon IBW are better
      predictive of engraftment after autologous and allogeneic HSCT. Sixty-three
      patients undergoing reduced-intensity HSCT after a uniform preparative regimen
      were evaluated to determine the effect of cell dose. ABW and IBW were 45-147 kg
      (median 79) and 52-85 kg (median 67) respectively. The ABW-IBW difference was 
      24% to +133% (median +16%); nine patients were >5% underweight and 41 were >5%
      overweight. The CD34+ cell dose (10(6)/kg) was 1.4-11.8 (median 5) by IBW and 1.2
      9.3 (median 4.5) by ABW. The CD3+ cell dose (10(8)/kg) was 0.9-14.9 (median 3) by
      IBW and 0.7-19.7 (median 2.7) by ABW. While CD34+ and CD3+ cell doses based upon
      IBW were found to affect transplant-related mortality, and disease-free and
      overall survival significantly, those based on ABW were either not predictive of
      outcome or the differences were of borderline significance. We suggest using IBW
      rather than ABW to calculate cell doses for HSCT; for statistical analyses and
      for clinical practice if a specific cell dose is being targeted.

PMID- 16444283
TI  - Elevated serum insulin-like growth factor binding protein-2 is associated with a
      high relapse risk after hematopoietic stem cell transplantation in childhood AML.
AB  - Insulin-like growth factor binding protein (IGFBP)-2 has mitogenic effects in
      normal and neoplastic cells. The purpose of this study is to examine the
      diagnostic and prognostic significance of elevated IGFBP-2 levels in children
      with AML after hematopoietic stem cell transplantation (HSCT) at relapse and
      continuous complete remission (CCR). In 27 children with AML (mean age 13.6+/-5.3
      years; patients in remission n=15 with relapse n=12) serum parameters of IGFBP-2,
      IGFBP-3, IGF-I and IGF-II were analyzed up to 18 months after HSCT by RIA. AML
      patients with evidence of relapse demonstrated a continuous increase of IGFBP-2
      levels during the follow-up. At day 100 after HSCT, IGFBP-2 concentrations were
      significantly higher in patients with relapse than in children without relapse
      (7.4+/-4.0 standard deviation score (SDS) vs 3.9+/-1.7 SDS; P=0.01). Serum IGFBP
      2 was identified as an independent factor for the prediction of relapse.
      Furthermore, the probability of relapse-free survival (RFS) in patients with
      IGFBP-2 >4.5 SDS at day 100 after HSCT was 31% compared to patients with IGFBP-2
      <4.5 SDS was 72% (P=0.004). Patients with IGFBP-2 concentration up to 4.5 SDS
      more likely developed a relapse and had a poorer outcome. Identification of these
      patients allows a more individualized and aggressive adjuvant treatment and
      follow-up.

PMID- 16444284
TI  - Preservation of ovarian function by ovarian shielding when undergoing total body
      irradiation for hematopoietic stem cell transplantation: a report of two
      successful cases.
AB  - The purpose of this study was to evaluate the possibility of preserving ovarian
      function by ovarian shielding to reduce the irradiation dose in total body
      irradiation (TBI). The subjects in the study were females aged less than 40
      years, who were undergoing allogeneic hematopoietic stem cell transplantation
      using a TBI-based regimen and who desired to have children after transplantation.
      For ovarian shielding, abdominal computed tomography (CT) and skin marking were
      performed in both the supine and prone positions, prior to the TBI. A pair of
      columnar blocks was placed just above the patient's body. Thus far three patients
      have been treated. The serum estradiol level decreased to an undetectable level
      (<8.5 pg/ml) after transplantation and the follicle-stimulating hormone (FSH)
      level increased above 90 mIU/ml in all patients and they became amenorrheic.
      However, regular menstruation recovered in patients no. 1 and 2 about 800 and 370
      days after transplantation, respectively, with a decrease in the serum FSH level.
      Menstruation did not recover in patient no. 3, and serum estradiol was
      transiently detected above 20 pg/ml. The preservation of ovarian function was
      made possible by ovarian shielding. However, a longer follow-up is needed to know
      if normal pregnancy and delivery can occur.

PMID- 16444285
TI  - Will a reduced-toxicity conditioning regimen improve the results of stem cell
      transplantation in metabolic disease?

PMID- 16444273
TI  - A SNP in the ABCC11 gene is the determinant of human earwax type.
AB  - Human earwax consists of wet and dry types. Dry earwax is frequent in East
      Asians, whereas wet earwax is common in other populations. Here we show that a
      SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination
      of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet
      type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of
      Asian ancestry. A functional assay demonstrated that cells with allele A show a
      lower excretory activity for cGMP than those with allele G. The allele A
      frequency shows a north-south and east-west downward geographical gradient;
      worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype
      is retained among various ethnic populations. These suggest that the allele A
      arose in northeast Asia and thereafter spread through the world. The 538G --> A
      SNP is the first example of DNA polymorphism determining a visible genetic trait.

PMID- 16444286
TI  - Allogeneic and autologous transplantation for haematological diseases, solid
      tumours and immune disorders: definitions and current practice in Europe.
AB  - The Accreditation Subcommittee of the EBMT regularly publishes special reports on
      current practice of haemopoietic stem cell transplantation for haematological
      diseases, solid tumours and immune disorders in Europe. Major changes have
      occurred since the first report was published in 1996. Haemopoietic stem cell
      transplantation today includes grafting with allogeneic and autologous stem cells
      derived from bone marrow, peripheral blood and cord blood. With reduced intensity
      conditioning regimens in allogeneic transplantation, the age limit has increased,
      permitting the inclusion of older patients. New indications have emerged such as
      autoimmune disorders and AL amyloidosis for autologous, and solid tumours for
      allogeneic transplants. The introduction of alternative therapies has challenged
      well-established indications such as imatinib for chronic myeloid leukaemia. An
      updated report with revised tables and operating definitions is presented here.

PMID- 16444287
TI  - Activation of nicotinic ACh receptors with alpha4 subunits induces adenosine
      release at the rat carotid body.
AB  - The effect of ACh on the release of adenosine was studied in rat whole carotid
      bodies, and the nicotinic ACh receptors involved in the stimulation of this
      release were characterized. ACh and nicotinic ACh receptor agonists, cytisine,
      DMPP and nicotine, caused a concentration-dependent increase in adenosine
      production during normoxia, with nicotine being more potent and efficient in
      stimulating adenosine release from rat CB than cytisine and DMPP. D-Tubocurarine,
      mecamylamine, DHbetaE and alpha-bungarotoxin, nicotinic ACh receptor antagonists,
      caused a concentration-dependent reduction in the release of adenosine evoked by
      hypoxia. The rank order of potency for nicotinic ACh receptor antagonists that
      inhibit adenosine release was DHbetaE>mecamylamine>D-tubocurarine>alpha
      bungarotoxin. The effect of the endogenous agonist, ACh, which was mimicked by
      nicotine, was antagonized by DHbetaE, a selective nicotinic receptor antagonist.
      The ecto-5'-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release
      of adenosine from CB evoked by nicotine. Taken together, these data indicate that
      ACh induced the production of adenosine, mainly from extracellular ATP catabolism
      at the CB through a mechanism that involves the activation of nicotinic receptors
      with alpha4 and beta2 receptor subunits.

PMID- 16444288
TI  - Red wine alcohol promotes quercetin absorption and directs its metabolism towards
      isorhamnetin and tamarixetin in rat intestine in vitro.
AB  - Moderate consumption of red wine has been associated with beneficial effects on
      human health, and this has been attributed to the flavonoid content. Factors that
      influence the bioavailability of this group of polyphenolic compounds are
      therefore important. Using the rat cannulated everted jejunal sac technique, we
      have investigated the effect of alcohol on the intestinal absorption of quercetin
      and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole
      or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37
      degrees C, after which the mucosa was removed and processed for HPLC analysis.
      Tissues exposed to red wine had significantly higher amounts of both quercetin (x
      3; P < 0.001) and quercetin-3-O-glucoside (x 1.5; P < 0.01) associated with them,
      compared with sacs incubated in the dealcoholised equivalent. In addition, both
      tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to
      the whole wine, were significantly elevated approximately two fold (P < 0.05; P <
      0.01, respectively). Similar results were obtained when sacs were incubated in
      Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside
      with or without alcohol, and, although effects on the apparent absorption of Q
      and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O
      glucuronide and I were significantly increased by the presence of alcohol (P <
      0.01 and P < 0.001, respectively). It is therefore plausible that the moderate
      alcohol content of red wine contributes to its beneficial health effects in
      humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside
      and by channelling their metabolism towards O-methylation to yield compounds (T
      and I), which have potential protective effects against cancer and cardiovascular
      diseases.

PMID- 16444289
TI  - Vanilloid VR1 receptor is involved in rimonabant-induced neuroprotection.
AB  - Recently, a potential neuroprotective effect of rimonabant, independent of the
      CB1 receptor interaction, has been proposed. In the present study, the role of
      transient receptor potential channel vanilloid subfamily member 1, named VR1, on
      neuroprotective effect of rimonabant, on global cerebral ischemia in gerbils, was
      investigated. Rimonabant (0.05-3 mg kg-1), given i.p. 5 min after recirculation,
      dose dependently antagonized the ischemia-induced decrease in
      electroencephalographic (EEG) total spectral power and restored relative
      frequency band distribution 7 days after ischemia. Rimonabant (0.125-0.5 mg kg-1)
      fully prevented ischemia-induced hyperlocomotion 1 day after ischemia and memory
      impairment evaluated in a passive avoidance task, 3 days after ischemia. At 7
      days after ischemia, the survival of pyramidal cells, in the CA1 subfield, was
      respectively 91 and 96%, in the animals given rimonabant 0.25 and 0.5 mg kg-1,
      compared to the vehicle group. Higher doses were not protective. The protection
      induced by rimonabant followed a bell-shaped curve, the maximal active doses
      being 0.25 and 0.5 mg kg-1. Capsazepine (0.01 mg kg-1), a selective VR1 vanilloid
      receptor antagonist, completely reversed rimonabant-induced neuroprotective
      effects against EEG flattening, memory impairment and CA1 hippocampal neuronal
      loss. These findings suggest that VR1 vanilloid receptors are involved in
      rimonabant's neuroprotection even if other mechanisms can contribute to this
      effect.

PMID- 16444290
TI  - Allosteric modulation, thermodynamics and binding to wild-type and mutant (T277A)
      adenosine A1 receptors of LUF5831, a novel nonadenosine-like agonist.
AB  - The interaction of a new nonribose ligand (LUF5831) with the human adenosine A1
      receptor was investigated in the present study. Radioligand binding experiments
      were performed in the absence and presence of diverse allosteric modulators on
      both wild-type (wt) and mutant (T277A) adenosine A1 receptors. Thermodynamic data
      were obtained by performing these assays at different temperatures. In addition,
      cyclic adenosine monophosphate (cAMP) assays were performed. The presence of
      allosteric modulators had diverse effects on the affinity of LUF5831, N6
      cyclopentyladenosine (CPA), a full agonist, and 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX), an inverse agonist/antagonist, for the adenosine A1
      receptor. PD81,723, for example, increased the affinity of CPA, while the
      affinity of LUF5831 was decreased. However, the affinity of DPCPX was decreased
      even more. In addition, LUF5831 was shown to have an affinity for the mutant
      (T277A) adenosine A1 receptor (Ki=122+/-22 nM), whereas CPA's affinity was
      negligible. The results of temperature-dependent binding assays showed that the
      binding of LUF5831 was entropy driven, in between the behaviour of CPA binding to
      the high- and low-affinity states of the receptor, respectively. The inhibition
      of the forskolin-induced production of cAMP through activation of the wt
      adenosine A1 receptor showed that LUF5831 had a submaximal effect (37+/-1%) in
      comparison to CPA (66+/-5%). On the mutant receptor, however, neither CPA nor
      LUF5831 inhibited cAMP production. This study indicates that the nonribose
      ligand, LUF5831, is a partial agonist for the adenosine A1 receptor.

PMID- 16444291
TI  - Pharmacological characterization of muscarinic receptor subtypes mediating
      vasoconstriction of human umbilical vein.
AB  - The present study attempted to pharmacologically characterize the muscarinic
      receptor subtypes mediating contraction of human umbilical vein (HUV).HUV rings
      were mounted in organ baths and concentration-response curves were constructed
      for acetylcholine (ACh) (pEC50: 6.16+/-0.04; maximum response 80.00+/-1.98% of
      the responses induced by serotonin 10 microM). The absence of endothelium did not
      modify the contractile responses of ACh in this tissue. The role of
      cholinesterases was evaluated: neither neostigmine (acetylcholinesterase
      inhibitor) nor iso-OMPA (butyrylcholinesterase inhibitor) modified ACh responses.
      When both enzymes were simultaneously inhibited, a significantly but little
      potentiation was observed (control: pEC50 6.33+/-0.03; double inhibition: pEC50
      6.57+/-0.05). Atropine, nonselective muscarinic receptors antagonist, inhibited
      ACh-induced contraction (pKB 9.67). The muscarinic receptors antagonists
      pirenzepine (M1), methoctramine (M2) and pFHHSiD (M3) also antagonized responses
      to ACh. The affinity values estimated for these antagonists against responses
      evoked by ACh were 7.58, 6.78 and 7.94, respectively. On the other hand, PD
      102807 (M4 selective muscarinic receptors antagonist) was ineffective against ACh
      induced contraction.In presence of a blocking concentration of pirenzepine,
      pFHHSiFD produced an additional antagonism activity on ACh-induced responses. The
      M1 muscarinic receptors agonist McN-A-343 produced similar maximum but less
      potent responses than ACh in HUV. The calculated pA2 for pirenzepine against McN
      A-343 induced responses was 8.54. In conclusion, the data obtained in this study
      demonstrate the role of M1 muscarinic receptor subtypes and suggest the
      involvement of M3 muscarinic receptor subtypes in ACh-induced vasoconstriction in
      HUV rings. In addition, the vasomotor activity evoked by ACh does not seem to be
      modulated by endothelial factors, and their enzymatic degradation appears to have
      little functional relevance in this tissue.

PMID- 16444292
TI  - Genomic disorders: molecular mechanisms for rearrangements and conveyed
      phenotypes.
AB  - Rearrangements of our genome can be responsible for inherited as well as sporadic
      traits. The analyses of chromosome breakpoints in the proximal short arm of
      Chromosome 17 (17p) reveal nonallelic homologous recombination (NAHR) as a major
      mechanism for recurrent rearrangements whereas nonhomologous end-joining (NHEJ)
      can be responsible for many of the nonrecurrent rearrangements. Genome
      architectural features consisting of low-copy repeats (LCRs), or segmental
      duplications, can stimulate and mediate NAHR, and there are hotspots for the
      crossovers within the LCRs. Rearrangements introduce variation into our genome
      for selection to act upon and as such serve an evolutionary function analogous to
      base pair changes. Genomic rearrangements may cause Mendelian diseases, produce
      complex traits such as behaviors, or represent benign polymorphic changes. The
      mechanisms by which rearrangements convey phenotypes are diverse and include gene
      dosage, gene interruption, generation of a fusion gene, position effects,
      unmasking of recessive coding region mutations (single nucleotide polymorphisms,
      SNPs, in coding DNA) or other functional SNPs, and perhaps by effects on
      transvection.

PMID- 16444293
TI  - Altered renal tubular expression of the complement inhibitor Crry permits
      complement activation after ischemia/reperfusion.
AB  - Ischemia/reperfusion (I/R) of several organs results in complement activation,
      but the kidney is unique in that activation after I/R occurs only via the
      alternative pathway. We hypothesized that selective activation of this pathway
      after renal I/R could occur either because of a loss of complement inhibition or
      from increased local synthesis of complement factors. We examined the
      relationship between renal complement activation after I/R and the levels and
      localization of intrinsic membrane complement inhibitors. We found that loss of
      polarity of complement receptor 1-related protein y (Crry) in the tubular
      epithelium preceded activation of the alternative pathway along the basolateral
      aspect of the tubular cells. Heterozygous gene-targeted mice that expressed lower
      amounts of Crry were more sensitive to ischemic injury. Furthermore, inhibition
      of Crry expressed by proximal tubular epithelial cells in vitro resulted in
      alternative pathway-mediated injury to the cells. Thus, altered expression of a
      complement inhibitor within the tubular epithelium appears to be a critical
      factor permitting activation of the alternative pathway of complement after I/R.
      Increased C3 mRNA and decreased factor H mRNA were also detected in the outer
      medulla after I/R, suggesting that altered synthesis of these factors might
      further contribute to complement activation in this location.

PMID- 16444294
TI  - X-ray scattering of non-crystalline biological systems using synchrotron
      radiation.
AB  - This tutorial review gives an overview of the progress in the study of non
      crystalline systems by X-ray scattering and closely related imaging techniques,
      made possible by advances in synchrotron radiation sources and instrumentation. A
      brief introduction to the techniques is followed by the presentation of a variety
      of recent applications to problems in fundamental and applied research in
      biochemistry and biophysics and food and pharmaceutical technology.

PMID- 16444295
TI  - Electrophoretic NMR studies of polymer and surfactant systems.
AB  - The aim of this tutorial review is to introduce to a broader readership the
      emerging technique of electrophoretic NMR (eNMR). The "electrophoretic" element
      of the technique refers to the fact that charged particles are induced to flow by
      the application of an electric field. This flow is measured using pulsed-gradient
      spin-echo NMR (PGSE-NMR). The great potential of this experimental approach is
      the fact that NMR is chemically selective and non-invasive. eNMR, especially when
      combined with the more established PGSE-NMR experiment, may therefore be used to
      quantify the structure of multi-component systems via the dynamics and charge of
      each species within a complex mixture. Accordingly, eNMR is likely to be of great
      significance for colloid scientists, biologists, technologists and formulation
      scientists.

PMID- 16444296
TI  - Azide rearrangements in electron-deficient systems.
AB  - The azide group has a diverse and extensive role in organic chemistry, reflected
      in the power of azide anion as a strong nucleophile, the role of organic azides
      as excellent substrates for cycloaddition reactions, the uses of azides as
      precursors of amines and nitrenes, and azide rearrangements known as the Curtius
      and Schmidt reactions. In recent years the scope of the Schmidt reaction has
      begun to be explored in depth, so that it now represents an important reaction in
      synthetic chemistry. This tutorial review analyses and summarises key recent
      developments in the field of Schmidt reactions.

PMID- 16444297
TI  - Hypercarbons in polyhedral structures.
AB  - Though carbon is mostly tetravalent and tetracoordinated, there are several
      examples where the coordination number exceeds four. Structural varieties that
      exhibit hypercarbons in polyhedral structures such as polyhedral carboranes,
      sandwich complexes, encapsulated polyhedral structures and novel planar aromatic
      systems with atoms embedded in the middle are reviewed here. The structural
      variety anticipated with hypercoordinate carbon among carboranes is large as
      there are many modes of condensation that could lead to large number of new
      patterns. The relative stabilities of positional isomers of polyhedral
      carboranes, sandwich structures, and endohedral carboranes are briefly described.
      The mno rule accounts for the variety of structural patterns. Wheel-shaped and
      planar hypercoordinated molecules are recent theoretical developments in this
      area.

PMID- 16444298
TI  - Charge on the move: how electron-transfer dynamics depend on molecular
      conformation.
AB  - This tutorial review illustrates the many facets whereby the molecular
      conformation helps to control the rates of through-bond electron transfer. A
      brief introduction to Marcus theory is given, highlighting the importance of the
      coupling element and the super-exchange mechanism, before considering the reasons
      why the coupling element might depend on the molecular geometry. The methods
      currently available for determination of both the coupling element and the
      geometry are reviewed and various examples are given for systems where the
      structure controls the degree of electronic coupling along the molecular axis.
      The role of the "bridge" connecting the donor and acceptor is emphasized.

PMID- 16444299
TI  - Power ultrasound in organic synthesis: moving cavitational chemistry from
      academia to innovative and large-scale applications.
AB  - Ultrasound, an efficient and virtually innocuous means of activation in synthetic
      chemistry, has been employed for decades with varied success. Not only can this
      high-energy input enhance mechanical effects in heterogeneous processes, but it
      is also known to induce new reactivities leading to the formation of unexpected
      chemical species. What makes sonochemistry unique is the remarkable phenomenon of
      cavitation, currently the subject of intense research which has already yielded
      thought-provoking results. This critical review is aimed at discussing the
      present status of cavitational chemistry and some of the underlying phenomena,
      and to highlight some recent applications and trends in organic sonochemistry,
      especially in combination with other sustainable technologies. (151 references.).

PMID- 16444300
TI  - Paraganglioma of the cerebellopontine angle. Case presentation and pathological
      considerations.
AB  - Paragangliomas (glomus tumors) arise from the extra-adrenal neuroendocrine
      system. They are benign but locally aggressive tumors, causing bone destruction
      and compression related symptoms. We present a case of paraganglioma of the
      cerebellopontine angle. Emphasis on possible difficulties in clinical, imaging or
      pathological identification, and surgical removal is done. To the best of our
      knowledge, only one more case was reported arising in the cerebellopontine angle.

PMID- 16444301
TI  - The follow-up of the efficacy of antiviral therapy at patients with chronic
      hepatitis C.
AB  - Hepatitis C virus infection can cause progressive liver injury and lead to
      fibrosis and eventually cirrhosis. Peginterferon alfa-2a represents a significant
      advance in the treatment of patients with chronic hepatitis C. The aim of the
      study was to investigate the efficacy, safety and tolerability of the therapy
      with Peginterferon alfa-2a plus Ribavirin in patients with chronic hepatitis C.
      The study was made on a number of 37 patients with chronic hepatitis C, admitted
      in Medical Clinic no. 1, Emergency County Hospital Craiova. The diagnosis of
      chronic hepatitis was established by means of clinical, biological and
      morphological investigations. Patients received 180 mug subcutaneously of
      Pegasys, once weekly, along with either 1000 or 1200 mg/day of Copegus, depending
      on their weight, for 48 weeks, with 24 weeks of treatment -- free follow-up. We
      evaluated: sustained virological response, histological response and adverse
      events. All patients were monitored using blood tests, control of viremia and
      liver functional tests. Analysis viral response revealed that 11 patients
      (29.72%) achieved sustained virological response. Histological response was
      obtained in 20 cases (54.05%) with chronic hepatitis C. The adverse events for
      Pegasys and Copegus combination therapy were reported in 21 cases (56.72%).
      Antiviral therapy had positive effect on subjective symptoms in almost half of
      patients included in our study. An improvement of liver functional tests was
      noted in the most cases. A third of patients who received Peginterferon alfa-2a
      plus Ribavirin had sustained virological response. Histological response was
      noted both at patients with sustained virological response and with unsustained
      virological response. The side effects of the antiviral treatment are frequent
      and the severe ones, which require dose reduction, are present at a low number of
      patients.

PMID- 16444302
TI  - Cytokines levels in prostate adenocarcinomas.
AB  - In this research, we determined the levels of IL-2, IL-6 and TNF-alpha at 60
      patients with prostate adenocarcinomas situated in II, III and IV stages. The
      method used was ELISA quantitative. We observed that the IL-2 levels were normal
      in II stage, and the levels of IL-6 and TNF-alpha were lightly increased. In III
      and IV stages of prostate cancer the levels of IL-2 were very low and the levels
      of IL-6 and TNF-alpha were very increased. The high levels of pro-inflammatory
      cytokines are correlated with diseases evolution. The decrease of IL-2 levels in
      advanced prostate cancer goes to the decrease of immune response in prostate
      cancer.

PMID- 16444303
TI  - Histiocytic sarcoma associated with Hodgkin's disease.
AB  - Histiocytic sarcoma is a rare malignant neoplasm. It is well-known the
      association of Langerhans' cell histiocytosis with Hodgkin's disease but only few
      cases of histiocytic sarcoma associated with Hodgkin's disease was reported. We
      present the case of 20-years-old female patient with Hodgkin's disease with a
      sternal tumor mass which was diagnosed as histiocytic sarcoma. The diagnostic was
      established immunohistochemically, using a large battery of antibodies (S-100, CD
      68, CD 34, CD 15, CD 30, Vim, NFAP) and by electron microscopy which revealed the
      lack of the Birbeck granules in the malignant proliferated histiocytes.

PMID- 16444304
TI  - Analysis of stress and displacements of phalanx bone with the finite element
      method.
AB  - In this paper analyze of phalanx bone supposed at compression, torsion and
      bending is made. We know that the bones are one of the most important natural
      composite materials. The finite element method offers the possibility for the
      study of the stress and the displacements which appears in different
      solicitations cases. We realized that the most solicited parts of the bone which
      will be the next broken parts, so the fracture are the once from the meeting of
      the bone's body with its hand. The observations made by studying 74 cases of
      fractures caused by torsion and compression and also made by the testing of 23
      phalanx bones confirm these conclusions.

PMID- 16444305
TI  - Correlations between the colic branches of the mesenteric arteries and the
      vascular territories of the colon.
AB  - The study, done on 100 corpses from the dissection rooms of anatomy laboratory,
      hinted the morphological variability of the colic arteries and their territories.
      Morphological variability of the colic branches derived from the mesenteric
      arteries (superior right colic artery -- 98%; middle right colic artery -- 88%;
      inferior right colic artery -- 100%; middle colic artery - 36%; superior left
      colic artery -- 100%; middle left colic artery -- 50%; inferior left colic artery
      -- 100%) allows us to give out a morphogenetic supposition related their
      ramification and number. Analyze of the results guide us to a tentative of
      setting down the vascular territories of the colon. In the beginning were
      established the territories of the mesenteric arteries (superior and inferior)
      and after that, were marked the subterritories for each colic artery.
      Establishing the vascular territories of the colic arteries have not only
      anatomical importance but also a surgical one, been known the difficult
      postoperatory colon's revitalization.

PMID- 16444306
TI  - Morphoclinical study of intracerebral haemorrhage with intraventricular
      extension.
AB  - AIMS: The study is an integrated assessment of clinical, image and morphological
      parameters in severe intracerebral haemorrhages (ICH) complicated with
      intraventricular extension (IVE). MATERIAL AND METHODS: The studied group had 93
      cases of patients with ICH and IVE who were hospitalized in the Emergency County
      Hospital of Craiova and died during hospitalization. The parameters evaluated
      were clinical (relation with the seasons, age, sex, arterial blood pressure, the
      motor deficit, degree of coma, Glasgow score at admission and medical care) and
      morphological (the sites of the intraparenchymal haematoma and IVE, the size of
      the intraparenchymal haematoma, the presence of the mass effect, perilesional
      oedema and subarachnoid effusion). The latter were assessed on CT films and
      during autopsy. RESULTS: The presence of IVE as a complication of ICH showed a
      predilection for cold seasons, especially autumn. From the 93 studied cases 51
      were men and 42, women. 52.6% of the patients were in the fifth and sixth life
      decade. Almost 80% of the patients had IIIrd stage arterial hypertension at
      admission, over 80% motor deficits and almost 60% Glasgow scores lower than 6.
      The ventricular effusion involved at least one of the lateral ventricles. The
      hematomas had huge dimensions as compared to hosting encephalic structures, in
      lobar sites involving more than one lobe. Other risk factors as mass effect and
      perilesional oedema were constantly present. CONCLUSIONS: The association of IVE
      with other independent risk factors such as hypertension, low Glasgow scores
      volume of intraventricular bleeding, dimensions of haemorrhagic foci, presence of
      mass effect and perilesional oedema results in the death of patient despite any
      sustained therapeutic intervention.

PMID- 16444307
TI  - Electronic microscopic evaluation of the Beta insular cells in type 2 diabetes.
AB  - In this work it has been done an electronic microscopic evaluation of the intra
      cytoplasmic organelle devices of the pancreatic beta insular cells in the type 2
      diabetes mellitus (insulin independent). The motivation of this study is the
      lesions noticed within another study, photonic microscopic, reason why we have
      considered it important to show up as well the interest modifications of the
      constitutive organelles of the beta insular cells.

PMID- 16444308
TI  - Tumoral stroma of salivary pleomorphic adenoma -- histopathological,
      histochemical and immunohistochemical study.
AB  - The aims of our paper were to establish the main histopathological, histochemical
      and immunohistochemical aspects of tumoral stroma from salivary pleomorphic
      adenomas. For this purpose we investigated 103 cases by the classical
      histopathological technique with paraffin embedding and staining with Hematoxylin
      Eosin (HE), Hematoxylin-Eosin-Safranin (HES), trichromic Masson, trichromic
      Goldner Szeckelly, orcein and Periodic Acid Schiff-Blue Alcian (PAS-AA).
      Immunohistochemically, they were investigated for AE1-AE3, MNF116, CK8, EMA,
      vimentin, alpha-actin calponin, S-100, GFAP, collagen IV, and PCNA. The results
      of our study suggest the key role of neoplastic myoepithelial cell in the
      achievement of diverse morphological aspects of stroma in such neoplasms.

PMID- 16444309
TI  - The role of histological examination for prognostic evaluation and therapeutic
      algorithm in urinary bladder tumors.
AB  - Pathological examination plays a major role in order to determine the prognostic
      and therapy of patients with urinary bladder tumors after a prior transurethral
      resection. The prognostic factors are studied to identify the risk of recurrence
      and tumoral progression of patients with superficial urothelial tumors and for
      appreciate the metastatic potential and response to therapy for patients with
      invasive carcinoma.

PMID- 16444311
TI  - Giant keratoacanthoma of the hand.
AB  - Giant keratoacanthoma (KA) is a very rare tumor which benefits of surgical
      treatment. We present a case of 61-years-old man with a giant keratoacanthoma
      situated on the dorsum of the right hand. The diagnosis is established by routine
      histopathologic examination.

PMID- 16444310
TI  - Uncommon pattern in soft tissues epithelioid sarcoma.
AB  - Epithelioid sarcoma (ES) is a rare tumor, but extremely versatile, simulating
      easily both clinically and morphologically multiple benign lesions as granulomas
      and malignant tumors as achromic melanomas or carcinomas. Especially the
      histological aspects are suggesting for an epithelial tumor. The atypical
      biological behavior of tumor is conferred by: a propensity for lymph nodes
      metastases, large dimensions of tumor, unusual localizations. AIM: To report some
      peculiar histological and immunophenotypic aspects in soft parts epithelioid
      sarcoma. MATERIALS AND METHODS: We analyzed retrospectively three cases of
      epithelioid sarcomas with unusual clinico-morphological (large dimensions),
      histopathological (absence of necrosis) and immunohistochemical (IHC) patterns
      selected from 200 consecutive soft parts malignant tumors of "Victor Babes"
      National Institute Bucharest files. For the immunohistochemical (IHC) staining,
      the following antibodies were used: vimentin, EMA, cytokeratins (KL1, CK19), S
      100 protein, CD68, p53 protein, vascular markers (CD31, CD34, FVIII-related
      antigen), HMB45, MELAN A. RESULTS: The tumors had unusually large dimensions, the
      absence of necrosis, a vaguely alveolar pattern; the IHC staining showed a strong
      positivity of S-100 protein, a variable expression of cytokeratins KL1 and CK19,
      in association to a scarce positivity for EMA, zonal positivity for CD34 and
      diffuse reaction for vimentin. CONCLUSION: The immunophenotype of ES may have a
      large variability and the correlation to clinico-morphological aspects is
      necessary for a good diagnostic assessment.

PMID- 16444312
TI  - Pseudo-tumoral lesions of the cervix.
AB  - Pseudo-tumoral lesions of the cervix implies some reactive, non-neoplastic
      changes (metaplasia, hyperplasia, inflammation) that, occasionally, are wrong
      interpreted as precancerous or malign lesions. Even some can present
      architectural or cytological abnormal aspects, these are different from the one
      noted in carcinomas or the precursor lesions of carcinomas. Them recognition is
      indispensable in order to avoid the diagnose errors and the super evaluation of
      these benign lesions.

PMID- 16444313
TI  - Study of cerebral vascular structures in hypertensive intracerebral haemorrhage.
AB  - AIMS: The study was performed in order to assess the alterations of extra
      parenchymal and intraparenchymal vascular structures in 82 hypertensive patients
      suspected of primary intraparenchymal hematoma, which died and were autopsied in
      order to confirm the diagnosis. MATERIAL AND METHODS: The studied material
      consisted of nervous tissue situated near and distant from the haemorrhagic
      lesion. The specimens of nervous tissue were processed by the classical
      histological technique and stained with the usual stainings and with
      immunohistochemical stains for basement membranes and endothelial cells. RESULTS:
      Extra-parenchymal arteries showed classic lesions of atherosclerosis.
      Atheromatous lesions were of all types, even the extension towards the media
      being encountered a complication with thrombosis. At the level of the
      intraparenchymal blood vessels, the spectrum of the lesions due to arterial
      hypertension included all steps of vascular wall degeneration, from hypertrophy
      of smooth muscle layer to complete hyalinization of arterial wall, but with a
      focal irregular distribution, not related with the proximity of haemorrhagic
      focus. High arterial blood pressure also influenced the capillary walls which
      showed focal or circumferential thickening due to the densification of the type
      IV collagen material from the basement membrane structure. The CD34
      immunostaining showed that endothelial cells kept their structural integrity.
      CONCLUSIONS: The sequence of degenerative lesions of the cerebral vascular wall
      culminates with the hyalinization of excessive fibrillar material form arteriolar
      wall or from basement membranes. Hyalin material is weakening the wall resistance
      to the stress determined by the high values of blood pressure in hypertension,
      and, correlated with a minimal resistance of the surrounding cerebral parenchyma,
      can explain why the cerebral parenchyma is the only tissue in which blood
      pressure variations can determinate vascular rupture and cerebral haemorrhage.
      The more adequate term for describing the vascular wall changes seems to be
      sclerosis (arteriolar and even capillary) with hyalinosis.

PMID- 16444317
TI  - [Current and future prospects in haemostasis].
AB  - Solving the human genome and new technical tools are nowadays rapidly increasing
      the knowledge of haemostasis. This includes the identification of novel genes,
      the understanding of complex phenotypes as thromboembolic disorders, the
      scientific exploration of the involved proteins by means of crystal structure,
      protein-protein-interactions and protein expression profiles as well as the
      development of new and more selectively acting anticoagulant drugs. The impact of
      haemostasis proteins in fields beyond haemostasis such as wound healing,
      angiogenesis, inflammation, immune system, and tumour growth is becoming more
      evident. Patients will profit from these developments by individualised
      prevention and therapy regimens, including future approaches of regenerative
      medicine as stem cell and gene therapy.

PMID- 16444316
TI  - [50 years GTH -- expectations, progress, disappointments. A personal
      perspective].
AB  - The Deutsche Arbeitsgemeinschaft fur Blutgerinnungsforschung (DAB) (German
      Working Party on Blood Coagulation) was founded in 1956 by a few German
      specialists in haemostasis. In 1982, the DAB was replaced by the Society on
      Thrombosis and Haemostasis (GTH), which was multinational, with emphasis on
      German speaking countries. Since I started in this field there was steady
      progress in the diagnosis and treatment of haemorrhagic and thrombotic disorders.
      Milestones were the production of effective and safe factor VIII and IX
      concentrates for haemophilia treatment, the diagnosis of venous thromboembolic
      disorders by non-invasive methods, the definition of thrombophilic states by
      laboratory methods and the diagnosis and treatment of immune coagulopathies. In
      other fields, progress was less impressive. During the last decades attempts have
      been made to optimize and standardize diagnosis and treatment in the thrombosis
      and haemostasis field (evidence based medicine). Despite guidelines and consensus
      statements the clinical problems in individual patients are still frequent and
      considerable. Therefore, physicians with a special expertise in the field of
      thrombosis and haemostasis are needed.

PMID- 16444318
TI  - [The management of patients with heparin-induced thrombocytopenia].
AB  - Heparin-induced thrombocytopenia is a strong risk factor for the development of
      arterial and venous thromboembolic events. In patients clinically suspected for
      HIT, immediate cessation of heparin treatment and continuation of anticoagulant
      treatment using alternative anticoagulants is mandatory in order to minimize the
      risk of thrombotic events. Alternative anticoagulants that have been successfully
      used in HIT include the direct acting thrombin inhibitors hirudin, bivalirudin
      and argatroban, and the heparinoid orgaran. In addition, there is growing
      evidence that the synthetic pentasaccharide fondaparinux is usable for the
      treatment of HIT patients. This short review summarizes the strategies of
      alternate anticoagulant treatment in HIT patients and also describes long-term
      treatment of HIT patients.

PMID- 16444319
TI  - [Global tests of haemostasis].
AB  - Global tests of haemostasis represent several reaction steps in the physiologic
      process of clotting. The proportion of plasma or whole blood in the test mixture
      of a global test is significantly higher than in clotting factor tests.
      Accordingly, the influence of preanalytical variables is strong, e.g. underlying
      diseases or drug effects. Strict adherence to preanalytical requirements is of
      utmost importance. Apart form the standardized reporting of the thromboplastin
      time (prothrombin time) as International Normalized Ratio (INR), results are
      generally not comparable when generated by using different reagents or
      instrumentation. Multiple potential influencing factors have to be considered
      when interpreting the results. Only laboratory requests precisely derived from
      the clinical situation can yield clinically relevant conclusions.

PMID- 16444320
TI  - Quantification of coagulation factors and inhibitors. Still a special task.
AB  - This is a very short review on quantitative coagulation factor assays for the
      beginner. For systematic training several excellent textbooks in German language
      are available. Quantitative functional assays of coagulation factors and of
      physiological inhibitor proteins are based on the principle of parallel-line or
      slope ratio bioassays. With the modern analyzers the test procedure follows the
      example of clinical chemistry: a single test plasma dilution read from an actual
      calibration curve, regular internal and external quality control. If there are
      unexpected results or a suspicion of haemophilia we recommend to repeat the assay
      with three different pre-dilutions of the test plasma. The resulting potency
      estimates should not deviate by more than 10-15% from their average. Otherwise
      the assay is invalid and requires further investigation (e.g. search for
      inhibitors). Special problems may complicate diagnostic activities. As an example
      discrepancies between factor VIII one-stage clotting and chromogenic assays are
      discussed.

PMID- 16444321
TI  - Primary haemostasis and its assessment by laboratory tests.
AB  - Platelets constantly patrol the inner surface of blood vessels searching leaks to
      be sealed, in order to prevent blood loss. When they detect a vessel injury their
      action can be divided into three phases. ADHESION: The platelets adhere to the
      injured blood vessel wall via their receptors glycoprotein (GP) Ib and integrin
      alpha2bbeta3 (GPIIb/IIIa) mediated by the ligands von Willebrand factor (VWF),
      fibrinogen and others. AGGREGATION: Platelets stick to each other through
      fibrinogen bridging integrin alpha2bbeta3 (GPIIb/IIIa) on adjacent platelets.
      SECRETION: During activation the content of platelet granules is released by
      exocytosis, thus augmenting and propagating formation of a haemostatic plug or
      thrombus. Laboratory tests mimic one or several aspects of these three phases to
      obtain reliable data on a patients platelet function. In this overview assays,
      test principles, and pitfalls are presented.

PMID- 16444322
TI  - Idiopathic venous thrombosis. Long-term anticoagulation therapy? Yes.
AB  - Idiopathic venous thromboembolism has been shown to be associated with a high
      frequency of recurrence. Therefore, the most important aim of long-term treatment
      is secondary prevention. It has also been shown that long-term anticoagulation
      with vitamin K antagonists can impressively reduce the rate of recurrence.
      However, this effect was only maintained during anticoagulation and disappeared
      after cessation of anticoagulant therapy. Unfortunately, the individual risk of
      recurrence is not predictable. Therefore, longterm anticoagulation appears
      beneficial across all subgroups of patients suffering from venous
      thromboembolism, regardless of the presence of thrombophilia or other burden of
      the disease. Despite the increasing body of evidence regarding the advantages of
      long-term anticoagulation, bleeding complications may limit the net clinical
      benefit of this strategy. Thus, the development of anticoagulants having a low
      potential for adverse reactions and providing similar beneficial antithrombotic
      effects to vitamin K antagonists will enhance the readiness for their wide spread
      use and life long administration.

PMID- 16444323
TI  - Idiopathic venous thrombosis. Long-term anticoagulant therapy? No.
AB  - Venous thrombosis is a chronic disease with a recurrence rate of approximately
      30% within 5-8 years. The optimal duration of secondary thromboprophylaxis in
      these patients entails balancing the risk of recurrence against the risk of
      treatment-associated bleeding. There is agreement that patients with a first
      idiopathic venous thrombosis should receive vitamin K antagonists for at least 3
      6 months. Convincing trials showing a clinical benefit in terms of morbidity or
      mortality with respect to expansion of anticoagulation beyond 6 months are
      lacking. Nevertheless, some subgroups of patients with venous thrombosis may
      benefit from indefinite anticoagulation. Thus, patients with antithrombin
      deficiency, combined or homozygous defects, more than one unprovoked episode of
      thrombosis, the lupus anticoagulant or high factor VIII plasma levels are good
      candidates for long-term prevention.

PMID- 16444324
TI  - [Inhibition of platelet aggregation for the secondary prevention after ACS: when
      clopidogrel instead of ASA, when clopidogrel and ASA?].
AB  - Long-term inhibition of platelet aggregation is essential for the secondary
      prevention after acute coronary syndromes (ACS). Inhibition of platelet
      aggregation with acetylsalicylic acid (ASA) has been established as a safe and
      effective therapy in this indication already end of the eighties in the preceding
      century. A decade later, with the introduction of the thieno-pyridines, combined
      platelet aggregation inhibition became possible. This opened the door for new
      treatment strategies in interventional cardiology. The first substance,
      ticlopidine was more or less replaced by the newer substance clopidogrel, which
      has improved pharmacological properties and less side effects. Low dose ASA (75
      mg/d) is still regarded as the standard therapy for secondary prevention after
      ACS. However, large clinical trials established clopidogrel as at least as
      effective and safe as ASA in this indication. Following PCI with bare metal stent
      implantation, a combined therapy of ASA and clopidogrel should be given for at
      least 4 weeks. After ACS with non-ST-elevation myocardial infarction the combined
      therapy with ASA and clopidogrel gives a better outcome than ASA alone. Recently
      published clinical trials show superiority of this strategy in patients with ST
      elevation myocardial infarction, too. If a combined long-term platelet
      aggregation inhibition with ASA and clopidogrel will be safe and more effective
      for secondary prevention is discussed.

PMID- 16444325
TI  - Thrombophilia and pregnancy complications.
AB  - Venous thromboembolism is the leading cause of pregnancy-associated morbidity and
      mortality. Women with thrombophilia have an increased risk of VTE in pregnancy
      and puerperium. In individuals with hereditary thrombosis risk factors a relative
      risk of pregnancy associated VTE ranging from 3.4 to 15.2 has been found. Women
      with previous VTE have an approximately 3.5-fold increased risk of recurrent VTE
      during pregnancy compared to non-pregnant periods. Data on the association of
      thrombophilia and pregnancy loss and pre-eclampsia are conflicting. Besides an
      established association with antiphospholipid antibodies, available data suggest
      associations for antithrombin deficiency, hyper-homo-cysteinemia, factor V
      Leiden, prothrombin G20210A variation and protein S-deficiency. A contribution of
      thrombophilia to the risk of pre-eclampsia is less well established. A limited
      number of prospective studies did not reveal an increased risk of pregnancy
      complications in unselected women with thrombosis risk factors. Data of only one
      controlled trial on the prevention of pregnancy loss with low molecular weight
      heparin (LMWH) are available, which revealed a strikingly positive effect.
      Thrombophilia screening might be justified in women with pregnancy loss and
      treatment with LMWH might be considered in those with pregnancy loss and
      thrombophilia. Further prospective studies and controlled interventional trials
      are urgently needed.

PMID- 16444326
TI  - [Pregnancy-associated venous thromboembolic disease: prediction, prevention, and
      therapy].
AB  - Thromboembolic disease remains a leading cause of maternal mortality during
      pregnancy and the puerperium. Rational and risk-adapted administration of heparin
      prophylaxis depends on 1. the identification of those women who have an increased
      risk of thrombosis and 2. the accurate quantification of this risk. In women
      without prior thrombosis, the presence of a heterozygous factor V Leiden or
      heterozygous G20210A mutation in the prothrombin gene is associated with a
      pregnancy-associated thrombotic risk of approximately 1 in 400. Thus, in pregnant
      carriers of either one of these mutations the risk of venous thromboembolism is
      low. Therefore, no heparin prophylaxis is recommended. A combination of the two
      genetic risk factors can increase the risk to a modest level of 1 in 25. In women
      with a single episode of prior thrombosis associated with a transient risk
      factor, e.g. surgery or trauma, and no additional genetic risk factor, the
      probability of a pregnancy-associated thrombosis appears also to be low. However,
      data are sparse and conflicting. In contrast, in women with a prior idiopathic
      venous thrombosis who carry an additional hereditary risk factor or who have a
      positive family history of thrombosis, a high risk (>10%) can be expected
      supporting the indication for active antepartum and postpartum heparin
      prophylaxis. Despite the remarkable progress in risk stratification, the absolute
      magnitude of risk and the optimal management in many cases is an issue of ongoing
      debate.

PMID- 16444327
TI  - Thrombocytopenia during pregnancy. Importance, diagnosis and management.
AB  - Thrombocytopenia is observed in 6 to 15% of pregnant women at the end of
      pregnancy, and is usually moderate. Gestational thrombocytopenia (defined as a
      mild thrombocytopenia, occurring during the 3 rd trimester with spontaneous
      resolution postpartum and no neonatal thrombocytopenia) is the most common cause
      of thrombocytopenia during pregnancy but a low platelet can also be associated
      with several diseases, either pregnancy specific or not, such as preeclampsia,
      HELLP syndrome, or idiopathic thrombocytopenic purpura (ITP). The differential
      diagnosis between ITP and gestational thrombocytopenia is clinically important
      with regard to the fetus, due to the risk of neonatal thrombocytopenia. However,
      this differential diagnosis is very difficult during pregnancy. Thrombocytopenia
      which need to be investigated are the following: thrombocytopenia known before
      pregnancy, thrombocytopenia occurring during the 1(st) and 2(nd) trimester,
      platelet count <75 G/l in the 3(rd) trimester or thrombocytopenia in case of
      pregnancy with complications. Investigations have to be discussed in function of
      history and clinical examination, gestational age and severity of
      thrombocytopenia. No treatment is required in case of gestational
      thrombocytopenia. There are few data to distinguish management of ITP between
      pregnant and non-pregnant women but management is different because of the
      potential adverse effects of the treatment for the woman and/or the fetus, the
      requirement for a good hemostasis at delivery and the risk of neonatal
      hemorrhage. One important problem is that it is not possible to predict the risk
      of neonatal thrombocytopenia in babies born from women with ITP.

PMID- 16444328
TI  - [The mandatory public record of clinical trials].

PMID- 16444330
TI  - [Can children with inguinal hernia be operated by a general surgeon?].

PMID- 16444329
TI  - [Is clear the role of anticoagulation in pulmonary hypertension?].

PMID- 16444331
TI  - [Diagnosis of urinary tract infections].

PMID- 16444333
TI  - [Mesenteric ischemia caused by embolism in atrial fibrillation].

PMID- 16444336
TI  - [Effectiveness of anorectal manometry using the balloon method to identify the
      inhibitory recto-anal reflex for diagnosis of Hirschsprung's disease].
AB  - OBJECTIVE: To evaluate results of anorectal manometry performed with equipment
      made in Brazil for the screening of Hirschsprung's disease in children with
      chronic constipation. METHODS: Results of 372 anorectal manometries performed
      consecutively in children with chronic constipation were evaluated. The equipment
      (Proctosystem Viotti) has two channels for pressure registration by the balloon
      method and is connected to a computer using specific software. Absence of the
      inhibitory recto-anal reflex was considered suggestive of Hirschsprung's disease
      and diagnosis was confirmed by traditional diagnostic methods. RESULTS: Absence
      of the inhibitory recto-anal reflex was found in 14 (3.8%) of the 372 anorectal
      manometry examinations. Diagnosis of Hirschsprung disease was confirmed in 9 out
      of 14 patients by characterization of aganglionosis upon rectal biopsy. In the
      other 5 patients, rectal biopsy was not performed in view of a satisfactory
      evolution with the clinical treatment for constipation. In 4 out of the 5
      patients the inhibitory recto-anal reflex was demonstrated with a second
      anorectal manometry examination. CONCLUSIONS: The equipment used for anorectal
      manometry presented a satisfactory performance. Diagnosis of Hirschsprung disease
      was discarded in 86.5% of the patients with chronic constipation because the
      inhibitory recto-anal reflex was detected. Manometric evaluation also made
      possible the identification of a small group of patients in which more than half
      had Hirschsprung's disease.

PMID- 16444337
TI  - [Assessment of mortality and specific index in acute renal failure].
AB  - A variety of systems of risk factor stratification have been studied to predict
      the outcome in acute renal failure (ARF). OBJECTIVES: Assess and compare
      mortality and the Acute Tubular Necrosis Individual Severity Score (ATN-ISS) in
      patients with AFR treated in a university hospital. METHODS: A prospective
      analysis was made of 103 patients with a diagnosis of intrinsic ARF admitted to
      the Hospital das Clinicas da Faculdade de Medicina de Botucatu, UNESP. Patients
      were followed up until recovery of renal function or death. The Score ATN-ISS was
      recorded during the first hours of the assessment by a nephrologist. Results were
      reported as median or mean +/- SD, with statistical significance of p < 0.05.
      RESULTS: Fifty-one percent of patients were male with a mean age of 58 +/- 36
      years. Forty-four percent died in the hospital. Mortality was higher in patients
      from the surgical wards (52.7%) and in patients who were treated with dialysis
      (63.8%). The score ATN-ISS showed a good confidence level, with high
      discriminatory power (area under the curve of 0.95) and good accuracy.
      CONCLUSIONS: Mortality in this study was comparable to that found in literature.
      The ATN-ISS was shown to be a prognostic index with a high confidence level that
      could be routinely applied by nephrologists to patients with AFR.

PMID- 16444338
TI  - [Evaluation of the efficacy of intravenous iron III-hydroxide saccharate for
      treating adult patients with iron deficiency anemia].
AB  - OBJECTIVE: To evaluate the efficacy of intravenous iron III-hydroxide saccharate
      for treating adult patients with iron deficiency anemia lacking satisfactory
      response to oral iron therapy. METHODS: Between January 2003 and January 2004, 25
      patients with iron deficiency anemia who presented intolerance or inadequate
      response to iron oral therapy, or hemoglobin level < 7 g/dl were studied. The
      main laboratory tests performed were: complete blood cell count, reticulocyte
      count, serum iron, total iron-binding capacity, serum ferritin. Patients received
      a weekly dose of 200 mg of iron diluted in 250 mL of 0.9% sodium chloride
      solution administered intravenously for 30 minutes. Treatment continued until a
      hemoglobin level = 12 g/dL for women and = 13 g/dL for men were obtained or until
      full administration of the total dose of parenteral iron recommended for each
      patient. RESULTS: Median age of the patients studied was 45 years (ages ranging
      from 31 to 70). Nineteen out of 25 patients (76%) were women. The most common
      cause of iron deficiency anemia was abnormal uterine bleeding observed in 68% of
      the female patients (13 out of 19) and partial gastrectomy observed in 67% of the
      male patients (4 out of 6). Seventeen (68%) patients were included in this study
      because they did not respond to oral iron therapy, 24% (6 out of 25) showed
      intolerance to oral iron and 8% (2 out of 25) presented hemoglobin level < 7
      g/dl. Correction of anemia was obtained in 12 out of 19 female patients (63%) and
      in 5 out of 6 male patients (83%). The mean hemoglobin and ferritin values were
      8.09 g/dl and 4.20 ng/ml (pre-treatment) and 12.42 g/dl and 87.78 ng/ml (post
      treatment) (p < 0.001), respectively. The average increase of hemoglobin was 3.74
      g/dl, ranging from 1.30 to 7.60 g/dl. None of the patients received blood
      transfusion during or after the intravenous iron treatment. CONCLUSION: The use
      of intravenous iron III-hydroxide saccharate is an efficacious and safe option in
      the treatment of adult patients with iron deficiency anemia lacking satisfactory
      response to oral iron therapy. This option of treatment should be considered
      mainly for patients with severe anemia in order to obtain rapid increase of the
      hemoglobin level and avoid blood transfusion.

PMID- 16444340
TI  - [Constipation in postmenopausal women].
AB  - OBJECTIVES: To investigate the prevalence and factors associated with
      constipation in postmenopausal women and evaluate the level of agreement between
      different diagnostic criteria. METHODS: A cross-sectional study was conducted
      with 100 postmenopausal women more than 45 old. The Rome II criteria, stool
      frequency per week and patient self-evaluation were the diagnostic criteria
      applied. Social demographic and clinical characteristics with their descriptive
      analysis were assessed. Subsequently, kappa (e) statistics was used to assess the
      level of agreement between diagnostic criteria. The association between
      constipation and its possible determinants was studied by bivariate and
      multivariate analyses, using the prevalence ratio (PR). The confidence interval
      was set at 95% (95% CI). RESULTS: The mean age of participants was 58.9+/-5.9
      years (range, 46-76 years). The prevalence of constipation was 47%, 37% and 26%,
      according to patient self-evaluation, the Rome II criteria and < 3 bowel
      movements per week, respectively. The best agreement found was between patient
      self-evaluation and the Rome II criteria (k: 0.63; 95% CI: 0.48-0.78). After
      multivariate analysis, the history of perianal surgery (PR: 2.69; 95% CI: 1.03
      7.01), according to the Rome II criteria; the presence of hemorrhoids, according
      to stool frequency (PR: 2.53; 95% CI: 1.16-5.51) and patient self-evaluation (PR:
      1.78; 95% CI: 1.01-3.15) were associated with constipation. CONCLUSIONS:
      Prevalence of constipation in postmenopausal women was high. Agreement between
      diagnostic criteria ranged from moderate to good. History of perianal surgery and
      presence of hemorrhoids were associated with constipation.

PMID- 16444339
TI  - [Well differentiated localized prostate carcinoma: prognostic relevance of
      tertiary Gleason pattern 4 and tumor volume].
AB  - INTRODUCTION: Early introduction of adjuvant radiation or hormone therapy after
      radical prostatectomy has been advocated in recent literature aiming to improve
      survival rates in high risk prostate cancer. Traditional prognostic parameters
      such as serum PSA, Gleason score and clinical stage have been used to identify
      these cases however accuracy is far from ideal. Recently, tumor volume and
      presence and percentage of a tertiary less differentiated Gleason pattern have
      been considered better indicators of prostate cancer behavior. The purpose of
      this study was to evaluate the importance of presence and percentage of a Gleason
      pattern 4 and of tumor volume in the outcome of patients treated for well
      differentiated prostate adenocarcinoma. METHODS: Seventy seven patients submitted
      to radical prostatectomy for well-differentiated prostate carcinoma, Gleason
      score 6 or less, and followed up for at least 5 years were selected. Thirty seven
      experienced biochemical recurrence while 40 did not. The percentage of Gleason
      pattern 4, the percentage of the gland involvement (considered as "tumor
      volume"), capsular invasion and extraprostatic extension were submitted to
      univariate and multivariate analyses for the evaluation of possible associations
      with biochemical recurrence. RESULTS: Tumor volume was the most important
      parameter to predict biochemical recurrence by univariate and multivariate
      analysis. The median of tumor volume was 25.0% for patients who suffered
      recurrence, and 11.5% for those with no recurrence (p=0.003). The percentage of
      Gleason pattern 4 was predictive of recurrence in univariate analysis only. The
      median percentage of Gleason pattern 4 was 7.5% for patients without recurrence
      and 19.0% for those who presented recurrence (p=0.046). CONCLUSION: Tumor volume
      is very objective, easy to evaluate and the most important parameter to predict
      biochemical recurrence in well-differentiated adenocarcinoma of the prostate. On
      the other hand, presence and percentage of a tertiary less differentiated Gleason
      pattern correlated with systemic relapse. Both parameters should be included in
      future studies to evaluate the role of adjuvant therapy in high risk prostate
      cancer.

PMID- 16444341
TI  - [Asthma related knowledge among parents of asthmatic children at the moment of
      admission to a specialized service].
AB  - OBJECTIVE: To assess asthma related knowledge among parents of asthmatic children
      at the moment of admission to a specialized service. METHODS: This was a
      descriptive study. Parents of 93 asthmatic children (aged from 29-18 yr) were
      interviewed, at the moment of admission to the Pediatric Pulmonary Outpatient
      Service of a university hospital, using a questionnaire to assess their asthma
      related knowledge. The assessment focused on understanding of the nature,
      prognosis and treatment of asthma. Only the data from parents of 87 children aged
      from 29 days to 10 years were analyzed. RESULTS: Upon self-assessment, 93.1% of
      the parents considered their asthma related knowledge insufficient and 88.5%
      showed interest in obtaining more information. With regard to understanding of
      the nature, prognosis and treatment of asthma, 96.6% of the parents did not know
      the role of airway inflammation on synthesis of symptoms and 51.7% believed in a
      cure for the disease. Among the parents whose children use a home nebulizer,
      80.6% used it incorrectly; all of the parents whose children use spray without a
      spacer were not familiar with the correct inhalation technique; 65.5% of the
      parents were unaware of the importance of environmental control. Presence of
      allergic sources and of smokers was found in 77.0% and 68.9% of families
      respectively. CONCLUSIONS: This study shows an insufficient asthma related
      knowledge among parents of asthmatic children at the moment of admission to a
      specialized service, characterized by ignorance about the nature and prognosis of
      the disease, inadequate technique to use inhaled drugs and unawareness of home
      environmental control.

PMID- 16444342
TI  - [Exploratory study of an emergency unit in Salvador, Bahia, Brazil].
AB  - OBJECTIVE: Analysis of patient care variables in an emergency unit that applies
      care protocols. METHODS:  SUBJECTS: Patients admitted to the emergency unit of
      the Sao Rafael Hospital in Salvador, Bahia, Brazil, between July 1, 2000 and May
      31, 2001. Study of the variables: age, gender, origin (city, district), admission
      date and hour, medical specialty, patient's disease (coded by ICDM-10), destiny
      (discharge, observation and discharge, observation and hospital admission),
      length of stay. RESULTS: 35.4% of the patients were under 14 years old. 86.11% of
      the admissions took place from 08:00 am to 10:59 pm. 78.96% of all patients were
      discharged after consultation. 17.86% required observation. Of these, 10.37% were
      discharged and 7.49% were admitted to the hospital. Length of stay was on the
      average of 282.9 (+/- 242.54) min. The ICDM-10 "R" group had a higher frequency,
      (29.5%). The three main causes for emergency unit admissions were fever, diarrhea
      and dyspnea. 12% of those who came from a distance of up to 5 km required
      observation and 5.8% needed hospital admission. 20.23% of those that came from a
      distance farther than 15 km required observation and 12.63% needed hospital
      admission. CONCLUSIONS: The majority of patients cared for in this emergency unit
      required low complexity care and the number increases when patients come to the
      hospital from a shorter distance.

PMID- 16444343
TI  - [Endocrine oncology: from research to the clinic a new/old stage for the
      performance of the endocrinologist].

PMID- 16444344
TI  - ["So, are we going to treat cancer now?"].

PMID- 16444345
TI  - [Pituitary tumorigenesis].
AB  - Pituitary adenomas, almost invariably adenomas, account for 10% to 15% of all
      intracranial neoplasms and are incidentally detected in up to 27% of non selected
      autopsies. They are morphologically classified as microadenomas (diameter < 1 cm)
      or macroadenomas, which can be enclosed, invasive and/or expansive. Functionally,
      they are classified as secreting adenomas (PRL, GH, ACTH, TSH, LH, and FSH, and
      those co-secreting two or more hormones), and clinically non secreting or "non
      functioning" tumors. Diagnosis is based on the hypersecretion phenotype
      (acromegaly, Cushing, etc), and on mass effect of macroadenomas leading to
      neurological disturbances, mainly visual complaints and headache. Pituitary
      tumorigenesis mechanisms include those of primary hypothalamic versus pituitary
      origin, the latter is supported by evidence of pituitary adenoma monoclonality,
      as well as the absence of hyperplastic tissue surrounding the surgically removed
      tumor, and the relative independence of tumor hypothalamic control. Nevertheless,
      a permissive role of the hypothalamus on tumor progression is also postulated.
      Several molecular mechanisms involved in pituitary tumorigenesis have been
      unraveled including oncogenes, tumor suppressor genes and growth factors involved
      in neoplastic development, and will be described in this review.

PMID- 16444346
TI  - Etiologic aspects and management of acromegaly.
AB  - Acromegaly is a systemic disease with various etiologies. It can occur as a
      sporadic or, more rarely, as a familial disease. Numerous complications such as
      endocrine, cardiovascular, respiratory, metabolic, osteoarticular and neoplastic
      disturbances occur and must be taken into account when establishing a therapeutic
      strategy. For this reason, the decision as to a treatment modality of acromegaly
      must be followed by a thorough evaluation of the patient and once the diagnosis
      of complications is settled, adequate treatment should be instituted. Follow up
      of the patients requires periodical re-assessment of complications status.

PMID- 16444347
TI  - [Dopamine-agonist resistant prolactinomas: diagnosis and management].
AB  - Prolactinomas are the more prevalent functioning pituitary tumors, and dopamine
      agonist drugs (DA) are the main therapeutic option for patients harboring such
      tumors. Bromocriptine (BRC) resistance, defined as failure to normalize prolactin
      (PRL) and/or to shrink the tumor is reported in 5 to 18% of the patients treated
      with this drug, the first DA widely used. Cabergoline (CBG) can bring PRL to
      normalization and reduce tumor size in up to 86% and 92% of the patients,
      respectively. Even with this newer DA, a subset of patients does not respond to
      therapy and are truly resistant. The mechanisms for resistance are not yet fully
      clarified, so the treatment for the resistant prolactinoma is still a challenge.
      Transsphenoidal surgery associated or not to radiotherapy is an important tool,
      but PRL may not normalize, mainly in macroprolactinomas. Treatment with sex
      steroids or ovulation induction can solve the hypogonadism or infertility, when
      the tumor growth is under control. New drugs as anti-estrogens, new DA, specific
      analogs for somatostatin receptor subtypes, chimeric molecules associating
      dopamine and somatostatin effect, and PRL antagonists are under investigation and
      can be future alternatives for DA resistance.

PMID- 16444349
TI  - [Glycoprotein-secreting pituitary adenomas: pathogenesis, diagnosis and
      treatment].
AB  - The glycoprotein-secreting pituitary adenomas comprise two distinctive clinical
      and pathological entities, the gonadotroph and the thyrotroph cell pituitary
      adenomas. Although they can be grouped together for producing hormones and/or
      subunits that are glycoproteins, these tumors originate from distinctive cell
      types (gonadotrophes and thyrotrophes) that are only remotely related.
      Gonadotroph cell adenomas are among the commonest types of pituitary adenomas,
      corresponding to the majority of the so-called "nonfunctioning" or clinically
      silent adenomas, while thyrotroph cell adenomas are extremely rare and usually
      present with hyperthyroidism due to inappropriate TSH secretion. In this article,
      we review the literature covering epidemiological, pathological, pathogenetic,
      clinical, diagnostic and therapeutic aspects of gonadotroph and thyrotroph cell
      adenomas. Greater emphasis was given to the growing field of molecular
      pathogenesis of pituitary tumors in general, and a special effort was made to
      contrast molecular alterations found in these tumors with other tumor types. On
      the practical side, the authors extensive experience for more than two decades in
      the diagnosis and management of these tumors at the Neuroendocrine Unit
      (Endocrinology Division, Unifesp) was used to balance the extensive literature on
      this subject.

PMID- 16444348
TI  - [Pituitary incidentalomas].
AB  - Clinically unsuspected pituitary lesions are demonstrated by magnetic resonance
      imaging in approximately 10% of the general adult population, characterizing the
      so-called pituitary incidentalomas. Their natural history is not yet completely
      established. Despite being typically small (<10 mm in the greatest diameter) and
      clinically silent, some pituitary incidentalomas may be hormonally active or
      cause mass effects by compressing neighboring structures. Furthermore, a minority
      of these lesions, particularly those greater than 10 mm (macroincidentalomas) may
      grow over time; hence, longterm follow-up is necessary. Therapeutic interventions
      are indicated for lesions that are hormonally active (use of dopamine agonists or
      transsphenoidal resection) or for those that cause mass effects or increase in
      size during the follow-up (transsphenoidal resection). Significant suprasellar
      extension or hypopituitarism may be additional indications for surgical treatment
      even in the absence of chiasm compression.

PMID- 16444350
TI  - [Nonpituitary tumors of the sellar region].
AB  - The pituitary gland, sella turcica and the parasellar region can be involved by a
      wide variety of lesions, including benign and malignant neoplasms as well as a
      wide variety of non neoplastic tumor-like lesions. Clinical and radiological
      aspects could help in the differential diagnosis of these lesions. Nevertheless,
      in many cases only the histopathological analysis could establish the definitive
      diagnosis. In this paper, we review the nonpituitary tumors of the sellar region
      emphasizing the associated hormonal disturbances.

PMID- 16444351
TI  - [Pathogenesis of differentiated thyroid cancer (papillary and follicular)].
AB  - Differentiated thyroid cancers (papillary--PTC and follicular--FTC) are the most
      common endocrine malignancies. The recent progresses in the understanding of PTC
      and FTC pathogenesis are summarized in this review. In PTC, a single mutation of
      BRAF (the gene for the B-type Raf kinase) (V600E) is responsible for the disease
      in 40-50% of patients, especially in older people and is associated with a poorer
      clinicopathological outcome. Due to these characteristics, its use as a specific
      diagnostic and prognostic marker for PTC in cytological specimens is being
      implemented. Another important cause of PTC is rearrangements of the RET tyrosine
      kinase receptor (RET/PTC), which represent a recombination of the promoter and N
      terminal domain of a partner gene with the C-terminal region of the RET gene,
      resulting in a chimeric gene with a protein product containing a constitutively
      activated RET tyrosine kinase, responsible for 20-30% patients, specially the
      younger or after radiation. The pathogenesis of FTC is less understood. A
      chromosomal translocation between the transcription factor PAX8 and the
      peroxisome proliferator-activated receptorgamma (PPARgamma) occurs in 30-50% of
      patients; however, the presence of PAX8-PPARgamma is also demonstrated in
      follicular adenomas. Therefore, there is no complete evidence that PAX8-PPARgamma
      is the cause of FTC. Another finding in FTC is mutations on the RAS gene, which
      excludes PAX8-PPARgamma rearrangements. Several genes, as TRgamma, PTEN, PKAR1A,
      DDIT3, ARG2, ITM1 and C1orf24--some discovered by techniques of differential gene
      expression--, have been recently implicated in the pathogenesis of FTC.

PMID- 16444352
TI  - [Differentiated thyroid carcinoma: initial evaluation and follow-up].
AB  - Thyroid carcinoma accounts for roughly 1% of all new malignant diseases. Of
      these, at least 94% are differentiated thyroid carcinoma (DTC), either papillary
      thyroid carcinoma or follicular thyroid carcinoma. Patients with DTC are usually
      considered as having a good prognosis, 80% of patients are cured, 20% will
      develop loco-regional recurrence and 5-10% distant metastasis. However, the
      disease may have an aggressive course in some patients. The identification of
      these patients has a major impact in the clinical management of DTC. Several
      prognostic factors and classification will be addressed, as well the most useful
      tests for patients follow-up.

PMID- 16444353
TI  - [Poorly differentiated thyroid carcinomas: new therapeutic considerations].
AB  - For most differentiated thyroid carcinomas, as papillary and follicular
      carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant
      ablation, treatment with thyroid hormones to suppress TSH levels will reduce the
      growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation
      therapy will either cure or control the disease. Thyroid carcinomas are
      considered poorly differentiated when they start to lose such functions as iodine
      uptake and thyrotropin-dependence for growth and production of thyroid proteins
      like NIS, thyroglobulin and desiodases. One of the greatest challenges in the
      management of patients with follicular cell-derived thyroid cancer is the
      treatment of tumors that progressed despite surgery, (131)I and T4 suppression of
      TSH. With the better knowledge of the abnormal molecular signaling in thyroid
      cancer cells, actually known targeted cancer therapies, directed against
      molecules involved in neoplastic transformation, are being used. As the critical
      molecular requirements for tumor initiation, maintenance and progression are
      identified, combination therapies with targeted agents acting on each of them
      will improve the treatment of poorly differentiated thyroid carcinoma.

PMID- 16444354
TI  - [Anaplastic thyroid carcinoma].
AB  - Well-differentiated thyroid carcinoma (TC), as papillary and follicular
      carcinoma, usually follows a relatively benign course after total thyroidectomy
      and thyroid remnant ablation with 131I. In contrast, anaplastic TC or
      undifferentiated TC, also derived from the thyroid follicular epithelium, refers
      to one of the more aggressive human malignancies, which have lost most or all
      characteristics of the tissue from which it originated. Rapid tumor growth
      presages early mortality unless combined therapy is aggressively pursued.
      Definitive curative approach does not exist for most patients. The best approach
      is still aggressive surgery combined with the associated use of new
      chemotherapies associated with local external beam radiotherapy.

PMID- 16444355
TI  - [Multiple endocrine neoplasia type 2].
AB  - The term multiple endocrine neoplasia (MEN) was introduced by Steiner et al. in
      1968 to describe disorders that include a combination of endocrine tumors. The
      Wermer syndrome was designed as MEN 1 and the Sipple syndrome as MEN 2. Sizemore
      et al. (1974) completed that the MEN 2 category included 2 subgroups: patients
      with medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid disease
      and a normal appearance (MEN 2A) and other without parathyroid disease but with
      mucosal neuromas and mesodermal abnormalities (MEN 2B). MTC is usually the first
      tumor diagnosed. The diagnosis of MTC has several implications: disease extent
      should be evaluated, pheochromocytoma and hyperparathyroidism should be screened
      and whether the MTC is sporadic or hereditary should be determined by a direct
      analysis of the RET proto-oncogene. Here, the pathological characteristics,
      genetic abnormalities, and clinical features of MEN 2 are discussed. The
      diagnostic and therapeutic approaches used to patients with clinical disease and
      carriers identified through familiar screening are also described. Progresses
      related especially to genetic screening and earlier intervention have permitted
      an improvement in the long-term outcome. However, treatment for disseminated
      disease is still ineffective.

PMID- 16444356
TI  - [Multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical and molecular
      diagnosis and treatment of the associated disturbances].
AB  - Multiple endocrine neoplasia (MEN) syndromes include types 1 (MEN 1) and 2 (MEN
      2), von Hippel-Lindau syndrome, neurofibromatosis type 1 and Carney complex.
      These are complex genetic syndromes caused by activation or inactivation of
      different types of genes known to be involved in the regulation of cell
      proliferation. In this review we will discuss the clinical manifestations and
      management of the MEN 1 syndrome as well as the genetic screening of potential
      MEN 1 gene carriers. MEN 1 is a hereditary syndrome, transmitted in an autosomic
      dominant fashion and caused by an inactivating mutation of the MEN 1 gene,
      characterized by the development of primary hyperparathyroidism, islet cell
      tumors and pituitary adenomas. In addition, these patients can present with
      cutaneous manifestations such as angiofibromas and collagenomas, and can develop
      other neoplastic manifestations including carcinoids, thyroid tumors, adrenal
      adenomas, lipomas, pheochromocytomas and meningiomas. The MEN 1 gene encodes a
      peptide which is a tumor suppressor gene called menin. Several studies have
      demonstrated its importance in regulation of cell proliferation and have
      confirmed its role in the pathogenesis of the MEN 1 syndrome. The discovery of
      the MEN 1 gene and the genetic analysis of MEN 1 patients have resulted in
      earlier diagnosis and treatment of asymptomatic carriers which can potentially
      result in a longer survival of these patients. Further investigation of the
      function and signaling pathways of the menin protein will hopefully offer
      therapeutic alternatives to patients with malignant progression of MEN 1-related
      tumors and also result in improved survival.

PMID- 16444357
TI  - [Treatment of childhood adrenocortical tumor].
AB  - Adrenocortical tumors (ACT) in children are uncommon. However, the incidence of
      these tumors in Parana is 15 times higher than that worldwide. A germline
      mutation, R337H TP53, present in more than 95% of our patients, is probably the
      reason for the higher incidence in our state. A hundred twenty-five patients were
      treated in the period of 1966 to 2003. Surgery is the only curative treatment. In
      our experience, disease stage I, absence of spillage during surgery and absence
      of intravenous thrombus are associated with better survival rates. Preliminary
      data with the combination of etoposide, doxorubicin, cisplatin, and mitotane have
      shown that in some patients a complete remission is observed both of the tumor
      and metastasis. Side effects due to these drugs are common and adrenal
      insufficiency may occur. Glucocorticoid and mineralocorticoid reposition should
      be done with 2 to 3 times the physiological doses.

PMID- 16444358
TI  - [Molecular mechanisms involved in adrenocortical tumorigenesis].
AB  - The adrenocortical tumorigenesis is a complex process, which involves multiple
      genetic changes. A better knowledge on the mechanisms involved in tumor
      development would enable an early identification of malignant disease and also
      lead to the development of new treatment strategies. Although in the recent years
      a large amount of data was produced, the exact mechanisms that lead to
      adrenocortical tumor development remains poorly understood. Most of the studies
      produced were based on the candidate-gene strategy, which has its own
      limitations. A genome-wide approach, such as microarrays, will surely shed some
      light into the mechanisms responsible for adrenocortical tumorigenesis. In this
      review, we summarize the most recent data available on this complex process.

PMID- 16444359
TI  - [Prevalence of adrenal incidentaloma at computed tomography (chest and abdominal)
      in a general hospital in Brazil].
AB  - OBJECTIVE: To prospectively determine the prevalence of incidental adrenal
      lesions at computed tomography (CT) at an University Hospital in Brazil. PATIENTS
      AND METHOD: A cross-sectional prospective study was performed to evaluate 3,382
      consecutive patients with no known adrenal disease or malignancies who underwent
      chest and abdominal CT scans over a ten-month period. The cases of adrenal
      incidentaloma were defined by the presence of any change in gland contour, size
      or density. Kappa values were calculated, evaluating the intra and inter-observer
      agreement. RESULTS: One hundred and one incidental adrenal masses were
      identified, corresponding to 83 cases and a prevalence of 2.5% (CI 95%: 1.0%
      3.2%). Male patients presented a higher prevalence of incidentaloma than female
      (3.3% vs. 1.5%; p= 0.01). There was a significant association between older age
      and higher frequency of incidentaloma. Kappa of 0.76 and 0.83 (good and excellent
      agreement, respectively), were obtained in evaluating the intra and inter
      observer agreements. CONCLUSIONS: The prevalence of adrenal incidentaloma
      detected by CT was similar to that of various published retrospective clinical
      series. The two factors that independently influenced the distribution of
      incidentalomas were older age and being male.

PMID- 16444360
TI  - [Granulosa-stromal tumor of the ovary: a case of mixed germ cell-cord stromal
      tumor of the ovary with endocrinological considerations].
AB  - Granulosa-stromal tumors comprise 5 to 8% of all primary ovarian neoplasms. The
      first clinical manifestation is precocious puberty in most prepuberal patients.
      We report a case of mixed germ cell-cord stromal tumor of ovary in a 7.2 years
      old girl, who presented with isosexual pseudo-precocious puberty of progressive
      outcome. Serum testosterone, estradiol and 17alphaOH-progesterone levels were
      increased. Abdominal-pelvic ultrasound revealed a right ovarian mass. Unilateral
      salpingo-oophorectomy was performed with complete resection of the tumor. The
      patient is well 7 years after surgery with normal pubertal and growth development
      and no signs of tumor relapse. We review the clinical manifestations of ovarian
      tumors, classification and staging of sex cord-stromal tumors, follow-up, tumor
      markers, treatment and prognosis.

PMID- 16444361
TI  - [Endocrine tumors associated to protein Gsalpha/Gi2alpha mutations].
AB  - Many oncogenic mutations promote tumor growth by inducing autonomous activity of
      proteins that normally transmit proliferative signal initiated by extracellular
      factors. G proteins are a family of guanine nucleotide binding proteins, which
      are structurally homologous and widely distributed in eukaryotic cells. They are
      composed of three different subunits (alpha, beta e gamma). The alpha subunit,
      which contains the guanine nucleotide-binding site, is unique to each G protein.
      The G proteins couple an array of seven transmembrane receptors at the cell
      surface with a variety of intracellular effectors, which produce second messenger
      molecules. A subset of endocrine tumors, such as GH- or ACTH-secreting pituitary
      adenomas, functioning thyroid adenomas, adrenocortical and gonadal tumors were
      associated with somatic activating mutations in the highly conserved codons of
      the Gs (Arg201 and Gln227) and Gi (Arg179 and Gln205) proteins. These findings
      indicated that the G proteins play a role as oncogenes, contributing with the
      human endocrine tumorigenesis.

PMID- 16444362
TI  - [Octreotide + bilateral adrenalectomy in the management of ACTH-producing
      carcinoid tumors].
AB  - Cushing's syndrome (CS) due to ectopic ACTH secretion has a high morbidity and
      mortality. Thus, rapid treatment of ectopic CS is mandatory. Carcinoid tumors
      associated with ectopic ACTH (CTu-ACTH) syndrome represent a more severe clinical
      picture, due to the carcinoid symptoms that worsen the hypercortisolism state.
      Management of patients with CTu-ACTH should include the control of
      hypercortisolism, as well as the carcinoid disturbance. We report 3 patients (2F,
      1M) with CTu-ACTH (2 pancreatic, 1 occult) who presented with clinical
      manifestations of CS (n= 3) and carcinoid syndrome (2): 2 were initially
      investigated for CS and 1 carcinoid syndrome. In all hypokalemia, hypertension
      and diabetes mellitus were associated with severe hypercortisolism and high ACTH
      levels. Administration of octreotide-LAR reduced ACTH levels from 230,000 to
      30,000 pg/ml in patient 1, and controlled symptoms of carcinoid syndrome and
      neoplasic lesions in patient 2; treatment with subcutaneous octreotide in patient
      3 controlled carcinoid syndrome and partially reduced symptoms of
      hypercortisolism. All 3 patients were submitted to bilateral adrenalectomy to
      control CS. Our data show that combined anti-neoplastic therapy may contribute to
      the stabilization and/or definitive control of CTu-ACTH.

PMID- 16444363
TI  - [Molecular biology in the prostate neoplasia].
AB  - Prostate cancer (PC) is one of the main causes of disease and death and
      represents the second cause of death among men in Brazil. Benign prostate
      hyperplasia is a progressive and prevalent disease. It is estimated that men
      present around 50% and 90% of histological evidences of prostate hyperplasia at
      50 and 80 years, respectively. While the pathogenesis of prostate neoplasias has
      been closely related to androgen and their specific nuclear receptor, the
      molecular mechanisms of cell growth, differentiation and apoptosis processes are
      still not clearly established. Co-activators and co-repressors could also
      contribute to prostate carcinogenesis by their binding to nuclear receptors or by
      interacting with the transcriptional machinery in order to increase the
      transcription of target genes. AR and type 2 5alpha reductase polymorphisms seem
      to be associated to the risk for PC. In addition, apoptosis and cellular cycle
      regulator genes, as well as growth factors, have been reported to be associated
      with the prostate tumorigenesis. Therefore, changes on the gene expression of
      normal tissue may be associated to the development of malign phenotype and these
      genes could be regarded as candidates of prognosis markers. The number of these
      genes increases every day but the present data needs further studies and
      correlation with the disease progression.

PMID- 16444364
TI  - [Polycystic ovary syndrome associated neoplasms].
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women on
      reproductive age. PCOS is characterized by the presence of anovulation,
      infertility and hyperandrogenism and is associated with obesity and insulin
      resistance. A major risk for neoplasms of the reproductive tract, like
      endometrial, breast and ovary cancer seems to be related to PCOS. While several
      studies have shown an increased risk for endometrial hyperplasia and cancer in
      PCOS patients, the variability of the selection criteria for PCOS has been
      recognized as a potential bias for these data. PCOS women also present clinical
      characteristics that are related to risk factors for breast cancer and some
      epidemiological evidences have been described on this issue. However, until now,
      a clear association between the presence of PCOS and breast carcinoma has yet not
      been found. Finally, high local steroid and growth factor concentrations are
      considered risk factors for ovary carcinoma, and are frequently observed in PCOS
      women. In turn, few studies have addressed the possibility of a link between PCOS
      and ovarian cancer and the results are conflicting but suggest that this
      association is unlikely.

PMID- 16444366
TI  - [Hypercalcemia of malignancy: clinical features, diagnosis and treatment].
AB  - Hypercalcemia associated with malignancies is reported in up to 20 to 30% of
      patients with cancer during the course of the disease, and points to a poor
      prognosis. Symptoms related to the central nervous system, as progressive mental
      impairment, stupor and coma, predominate. Alterations in kidney function (water
      concentrating defect leading to polyuria) and gastrointestinal tract (anorexia,
      nausea, vomiting) corroborate to dehydration and a further increase in serum
      calcium. Cancer-induced hypercalcemia may be classified as: 1) local osteolytic
      hypercalcemia (LOH), due to marked increase in osteoclastic bone resorption in
      areas surrounding the malignant cells within the marrow space; 2) humoral
      hypercalcemia of malignancy, caused by the secretion of parathyroid hormone
      related protein (PTHrP) by the malignant tumor; 3) ectopic hyperparathyroidism;
      4) 1,25(OH)2 D-secreting tumors. Adequate control of hypercalcemia is necessary
      to give the patient time to respond to anti-cancer therapy. Volume expansion with
      saline will correct dehydration, improve glomerular filtration and increase
      urinary calcium excretion, which may be further stimulated by loop diuretics.
      Intravenous bisphosphonates are the most effective agents to control
      hypercalcemia, as they block osteoclastic osteolysis and also have antitumoral
      effects, decreasing bone metastases. New approaches to control the skeletal
      manifestations of malignancies are anti-PTHrP and anti-RANKL antibodies,
      osteoprotegerin, and also proteasome inhibitors in the case of multiple myeloma.

PMID- 16444365
TI  - [Parathyroid carcinoma].
AB  - Parathyroid carcinoma is a rare condition, comprising less than 1% of the cases
      of primary hyperparathyroidism (PHP). Nonetheless, due to its aggressiveness, and
      having prognosis dependent on the precocity of diagnosis and radical therapeutic
      approach, it is paramount that the clinical suspicion be made before surgery.
      Clinical presentation is typical of severe PHP, with a parathyroid tumor >1.5 cm,
      usually palpable. The pathologic features sometimes are difficult to
      characterize. Our experience with this condition (from 1983 to 2004) includes 7
      cases, all symptomatic, hypercalcemic syndrome and bone disease present in most
      of them. In 6/7 the tumor was palpable, and in all the biochemical profile was
      compatible with severe PHP. Three patients died of complications of
      hypercalcemia. Recent findings point to a mutation on the gene HRPT2 as the
      molecular base for the development of this kind of tumor. The therapeutic
      approach is surgical and should include ipsilateral thyroidectomy and cervical
      exploration in order to find possible local metastasis. Post-surgical
      complications (mainly hypocalcemia) are proportional to the pre-existing
      metabolic alterations. The long-term prognosis depends upon the precocity of
      diagnosis, surgical success and control of hypercalcemia. New therapeutic
      approaches, based on bisphosphonates and calcimimetic drugs, as well as the
      possibility of genetic diagnosis, tend to ameliorate the prognosis of this severe
      affection.

PMID- 16444367
TI  - [Endocrine sequelae after radiotherapy in childhood and adolescence].
AB  - Radiotherapy may result in endocrine abnormalities, osteoporosis, obesity and
      neurological sequelae in patients treated for cancer. In the hypothalamo
      pituitary area, GH deficiency is the most frequent complication. The frequency,
      delay of appearance and severity of GH deficiency depend most on the dose
      delivered during cranial irradiation but variables as age at treatment and
      fractionation schedule may play an important role as well. Other hypothalamo
      pituitary dysfunctions are also dose-dependent. Low dose cranial irradiation may
      induce precocious or early puberty, while high doses are related to gonadotropin
      deficiency. Endocrine complications due to extracranial irradiation such as
      gonadal or thyroid abnormalities are described. In spite of normal GH secretion,
      linear growth may be impaired by bone lesions secondary to craniospinal or total
      body irradiation. Results on final height have been optimized by better
      indicators of GH therapy associated with adequate treatment of early or
      precocious puberty. The purpose of this review is to explore the late endocrine
      sequelae of radiotherapy.

PMID- 16444368
TI  - [GH/IGF-1 and cancer: what's new in this association].
AB  - Evidence from in vitro and animal studies suggests that members of the insulin
      like growth factors (IGFs) system, including IGF-I, IGF-II, the IGF-I receptor
      (IGF-IR), and the IGF-binding proteins (IGFBPs) play a central role in the
      development and progression of cancer. More specifically, IGFs may promote cell
      cycle progression and inhibition of apoptosis either by directly associating with
      other growth factors or indirectly by interacting with other molecular systems,
      which have an established role in carcinogenesis and cancer promotion. In
      addition, a growing number of epidemiologic studies suggest that increased serum
      levels of IGFs and/or altered levels of their binding proteins are associated
      with increased risk for developing several malignancies. This review aims to
      summarize and to show the role of IGF system in tumor regulation, a revision of
      epidemiologic studies and the risk of neoplasia in patients (with or without
      personal history of previous neoplasia) who received growth hormone (rhGH). It is
      important to emphasize that the clinical use of rhGH, in the indications
      internationally approved, is secure, and there are not evidences, at this moment,
      of the association with neoplasias development.

PMID- 16444369
TI  - [Acromegaly and thyroid disease: prevalence of thyroid cancer].
AB  - The relationship between cancer and acromegaly has been subject of study for many
      years. From a case of differentiated thyroid carcinoma in one of our acromegalic
      patients, we reviewed a series of 100 acromegalics and found two others cases of
      thyroid cancer, which are described in this work. From that point, we have got
      data from the literature about this last association and its possible
      pathogenesis. The prevalence of thyroid disease is increased among acromegalic
      patients, mainly due to nodular goiter. This association will be discussed, as
      well as the relation between insulin-like growth factor-I and cancer, in an
      effort to have a better understanding of its meaning for our cases. We concluded
      that it would be prudent to do periodic ultrasonographic evaluation of
      acromegalic patients, follow by fine needle aspiration biopsies of suspect
      nodules.

PMID- 16444370
TI  - Carcinoid syndrome: diagnosis and medical management.
AB  - Gastro-intestinal carcinoids are slow growing tumors arising from
      enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what
      combination of bioactive substances is secreted. Midgut carcinoid can present
      with the carcinoid syndrome in the presence of liver metastases. Its most typical
      clinical manifestations include cutaneous flushing and diarrhea. A nonspecific
      biochemical tumor marker for carcinoid tumors is serum chromogranin A and a
      specific marker for the carcinoid syndrome is the increased urinary excretion of
      5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid
      tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic
      US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging,
      selective abdominal angiography, 111In-pentetreotide scintigraphy (and
      intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG)
      scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET).
      Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs,
      interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)
      embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation
      of liver metastases, cryosurgery of liver metastases, occasionally liver
      transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and
      occasionally chemotherapy.

PMID- 16444371
TI  - [Increase the disabsorptive component: possible remedial procedure for failure
      after Roux-en-Y gastric bypass].

PMID- 16444372
TI  - [Gastric bypass Roux-en-Y gastrojejunostomy--conversion to distal
      gastrojejunoileostomy for weight loss failure--experience in 41 patients].
AB  - BACKGROUND: Surgery is the only effective treatment for morbid obesity. Gastric
      bypass could fail in up to 10% of the patients (excess weight loss under 50%).
      AIMS: To evaluate the weight loss determined by reoperation performing
      disabsortive variation of gastric bypass. PATIENTS AND METHODS: The records of 41
      patients, in whom 32 were submitted to reoperation by one of three surgical
      techniques (Fobi, Brolin, distal gastrojejunoileal bypass) which consisted in
      increasing the disabsortive length of intestinal limb. RESULTS: The patients
      submitted to distal gastrojejunoileal bypass showed the best results (69.7%).
      CONCLUSION: The distal gastric bypass as a revisional procedure could be done in
      selected cases with the aim to improve the weight loss. It is advisable to refer
      these patients to selected centers (known as center of excellence) with
      experience in this area of bariatric surgery, in order to perform a very close
      follow-up.

PMID- 16444373
TI  - [Bone mineral density evaluation in inflammatory bowel disease patients].
AB  - BACKGROUND: Inflammatory bowel disease patients have shown greater reduction of
      the bone mineral density compared to healthy people. AIM: To evaluate the bone
      mineral density in a population of patients with inflammatory bowel disease.
      METHODS: Ninety patients from 20 to 50 years old, of the Inflammatory Bowel
      Disease Ambulatory of the Gastroenterology Service of the Clinics Hospital,
      Curitiba, PR, Brazil, were selected for the evaluation. From those, 76 completed
      all the stages of the evaluation. The densitometry was made from lumbar column
      and right femur with a dual-energy x-ray absorptiometry (Hologyc QDR 1000/W)
      device. RESULTS: The inflammatory bowel disease patients had a significant
      reduction of the bone mineral density in all the evaluated parts, femur neck,
      total femur and lumbar column. The analysed variables, disease activity index,
      usage of corticoids, the lack of physical activities, the index body mass and
      previous surgeries did not have influence in the results. CONCLUSION: Reduced
      bone mineral density was founded in inflammatory bowel disease patients of the
      Clinics Hospital, mainly in the Crohn's disease patients, as described in
      literature. None analyzed variables had significant correlation to the bone
      mineral density.

PMID- 16444374
TI  - [The impact of intra operative ultrasound in metastases liver surgery].
AB  - BACKGROUND: Twenty-five to 50% of the patients with hepatic metastases are
      potential candidates for curative surgery. Intraoperative ultrasound has been
      employed to guide the surgery. AIM: To evaluate this method in liver surgeries
      and compare it to other imaging methods. PATIENTS AND METHODS: Thirty-five
      patients (20 females, with median age of 56 years) with hepatic metastases were
      prospectively studied between February 2001 and July 2003. Patients had as
      primary tumors: colorectal cancer (24), neuroendocrine tumors (3), renal cell
      carcinoma (2), melanoma (2), others (4). Each patient was submitted to at least:
      computed tomography (30), ultrasonography (14) and magnetic resonance imaging
      (8). Intraoperative ultrasound was performed in all patients in order to detect
      liver nodules. The number and location of liver lesions were compared to
      preoperative results. RESULTS: Intraoperative ultrasound was useful in 23 (65.6%)
      of the 35 surgeries and changed the planned surgical strategy in 9 (25.7%). There
      was a statistical significant correlation between the mean number of nodules
      identified by ultrasonography, computed tomography, magnetic resonance imaging
      and intraoperative ultrasound. We found no statistical difference between
      magnetic resonance imaging and intraoperative ultrasound in identifying hepatic
      nodules. Fifty-five nodules were submitted to histological evaluation, the gold
      standard method and 52/55 (94.5%) were identified by intraoperative ultrasound.
      Intraoperative ultrasound identified 91.6% of the smaller than 1.5 cm lesions,
      ultrasonography identified 15.0% of them, computed tomography 33.3% and magnetic
      resonance imaging 66.6%. CONCLUSIONS: Intraoperative ultrasound is crucial in the
      evaluation and decision making in hepatic surgery. Intraoperative ultrasound
      presents the highest sensibility in the detection of hepatic nodules compared to
      other imaging methods, especially for small lesions.

PMID- 16444375
TI  - [Esophageal motor disorders in cirrhotic patients with esophageal varices non
      submitted to endoscopic treatment].
AB  - BACKGROUND: The hepatic cirrhosis has as one of the main morbid-mortality causes,
      the portal hypertension with the development of esophageal varices, the
      possibility of a digestive hemorrhage and worsening of hepatic insufficiency. It
      is important to identify causal predictive or aggravating factors and if possible
      to prevent them. In the last years, it has been observed the association of
      esophageal motor disorders and gastro-esophageal reflux in cirrhotic patients
      with esophageal varices. AIMS: To study the prevalence of the esophageal motility
      disorders and among them, the ineffective esophageal motility, in patients with
      hepatic cirrhosis and esophageal varices, without previous endoscopic therapeutic
      and the predictive factors. METHODS: Prospectively, it has been evaluate 74
      patients suffering from liver cirrhosis and esophagic varices, without previous
      endoscopic treatment. All of them were submitted to a clinical protocol,
      esophageal manometry and 55 patients also held the ambulatory esophageal pHmetry.
      RESULTS: Esophageal motility disorders have been found in 44 patients (60%). The
      most prevalent was the ineffective esophageal motility, observed in 28%. The
      abnormal reflux disease was diagnosed through the pHmetry in 35% of the patients.
      There were no correlation between the manometrical abnormality in general and the
      ineffective esophageal motility in particular and the esophageal or
      gastroesophageal reflux disease symptoms, the abnormal reflux, the disease
      seriousness, the ascites presence and the gauge of the varices. CONCLUSIONS: The
      majority of cirrhotic patients with non-treated esophageal varices present
      esophageal motor disorders. No predictive factor was found. The clinical
      relevance of these findings need more researches in the scope to define the real
      meaning of theses abnormalities.

PMID- 16444376
TI  - High serum laminin and type IV collagen levels in schistosomiasis mansoni.
AB  - BACKGROUND: Fibrosis is the process of excessive deposition of collagen and other
      extra cellular matrix components and large amounts of these components have been
      shown in periovular schistosomal granulomas, especially in the liver. Laminin and
      type IV collagen have been investigated in various hepatic disorders but their
      accuracy in fibrosis detection and in the evaluation of its progression in
      schistosomiasis have not been fully explained. AIM: To measure the serum levels
      of two markers of fibrosis, laminin and type IV collagen in schistosomiasis.
      PATIENTS AND METHODS: Sixty-four patients with different clinical forms of
      schistosomiasis mansoni: intestinal (group I), hepatointestinal (group II),
      compensated (group III) and decompensated hepatosplenic (group IV) and 18 healthy
      volunteers were included. RESULTS: Serum type IV collagen and laminin levels were
      significantly increased in patients compared to controls. At about clinical
      forms, serum type IV collagen was increased in groups II and IV, compared to
      controls and was significantly higher in group IV than in group I. Serum laminin
      was significantly increased in groups II, III and IV and was significantly higher
      in group IV than in group II. Serum type IV collagen was closely correlated with
      serum laminin in groups II and IV. CONCLUSIONS: Connective tissue marker levels
      did not correlate with periportal thickness. In schistosomiasis mansoni there is
      an increase of type IV collagen and laminin levels at the initial stage of the
      disease, as well as in advanced forms. We also suggest that these markers may be
      a useful predictor of disease progression.

PMID- 16444377
TI  - [Importance of the tridimensional ultrasound in the anorectal evaluation].
AB  - BACKGROUND: Anorectal endosonography is actually the main image exam to evaluate
      some anorectal diseases. AIM: To show the three-dimensional endosonography
      importance in the anal canal anatomic evaluation and the anorectal diseases
      diagnosis. METHODS: Seventy four anorectal ultrasound were performed, 23 normal
      individuals (13 women) and 51 patients (33 women) with benign and malignant
      diseases. All the patients were examined with a 3-D equipment with 360 degrees
      transducer. Normal individuals were evaluated in midline sagittal plane
      concerning to the length of the anal canal, the internal anal sphincter, the
      external anal sphincter and the anatomic defect in the anterior quadrant.
      RESULTS: There were no differences in the anal canal and the internal anal
      sphincter length between men and women. Otherwise, the external anal sphincter
      length is longer in men and the anatomic defect is longer in women. In those with
      anorectal diseases, 11 sphincter injuries, 8 anal fistulas, 7 abscess, 1
      perirectal endometriosis, 1 pre-sacral cyst, 3 anal canal and 10 rectal malignant
      neoplasias were diagnosed. The surgical findings confirmed the ultrasound
      diagnosis in all the patients. CONCLUSION: Three-dimensional endosonography
      demonstrated the anatomic differences between male and female anal canal,
      justifying the larger incidence of pelvic floor disorders in female patients. It
      was possible to diagnose the anorectal diseases, in multi-plane, with high
      spatial resolution, adding also important informations about the therapeutic
      decision. Such characteristics become it similar to nuclear magnetic resonance
      with intra-rectal coil, with the advantages to be easier, quicker, low cost and
      better tolerated.

PMID- 16444379
TI  - Echo-endoscopy versus endoscopic retrograde cholangiography for the diagnosis of
      choledocholithiasis: the influence of the size of the stone and diameter of the
      common bile duct.
AB  - BACKGROUND: Endoscopic retrograde cholangiography is highly accurate in
      diagnosing choledocholithiasis, but it is the most invasive of the available
      methods. Endoscopic ultrasonography is a very accurate test for the diagnosis of
      choledocholithiasis with a risk of complications similar to that of upper
      gastrointestinal endoscopy. AIM: To compare the accuracy of endoscopic
      ultrasonography and endoscopic retrograde cholangiography in the diagnosis of
      common bile duct stones before laparoscopic cholecystectomy and to analyze
      endoscopic ultrasound results according to stone size and common bile duct
      diameter. PATIENTS AND METHODS: Two hundred and fifteen patients with symptomatic
      gallstones were admitted for laparoscopic cholecystectomy. Sixty-eight of them
      (31.7%) had a dilated common bile duct and/or hepatic biochemical parameter
      abnormalities. They were submitted to endoscopic ultrasonography and endoscopic
      retrograde cholangiography. Sphincterotomy and sweeping of the common bile duct
      were performed if endoscopic ultrasonography or endoscopic retrograde
      cholangiography were considered positive for choledocholithiasis. After
      sphincterotomy and common bile duct clearance the largest stone was retrieved for
      measurement. Endoscopic or surgical explorations of the common bile duct were
      considered the gold-standard methods for the diagnosis of choledocholithiasis.
      RESULTS: All 68 patients were submitted to laparoscopic cholecystectomy with
      intraoperative cholangiography with confirmation of the presence of gallstones.
      Endoscopic ultrasonography was a more sensitivity test than endoscopic retrograde
      cholangiography (97% vs. 67%) for the detection of choledocholithiasis. When
      stones >4.0 mm were analyzed, endoscopic ultrasonography and endoscopic
      retrograde cholangiography presented similar results (96% vs. 90%). Neither the
      size of the stone nor the common bile duct diameter had influence on endoscopic
      ultrasonographic performance. CONCLUSIONS: For a group of patients with an
      intermediate or moderate risk with respect to the likelihood of having common
      bile duct stones, endoscopic ultrasonography is a better test for the diagnosis
      of choledocholithiasis when compared to endoscopic retrograde cholangiography
      mainly for small-sized calculi.

PMID- 16444378
TI  - [Does the criterium of positivity for the immunohistochemical analysis of p53 in
      the confirmation of Barrett's dysplasia make any difference?].
AB  - BACKGROUND: Barrett's esophagus is the most serious complication of the
      gastroesophageal reflux disease and presents a malignant potential. The
      expression of the tumoral marker p53 increases with the dysplasia-adenocarcinoma
      sequence. AIMS: To evaluate the p53 expression in Barrett's esophagus with or
      without dysplasia according to the two positive immunostaining criteria.
      MATERIALS AND METHODS: The material was constituted by endoscopic biopsy
      specimens from 42 patients with Barrett's esophagus. Section of formalin-fixed
      and paraffin-embedded biopsies were stained with hematoxylin-eosin, PAS-alcian
      blue and evaluated the p53 immunohistochemical expression. Two p53 immunostaining
      criteria were utilized: 1. The staining of, at least, half of the nuclei, and 2.
      The staining of any nucleus. The diagnosis of dysplasia was confirmed by the
      agreement between three pathologists. RESULTS: The total number of tissue
      specimens was 229, with an average of 5.4 specimens per patient. Dysplasia, with
      agreement for all pathologists examining the same set of slides, was detected in
      six (14.3%) cases. According to the two different p53 immunostaining criteria,
      the protein was detected in non-dysplastic Barrett's metaplasia, respectively, in
      5 (13.9%) and 14 (38.9%) patients. Specifically in the six dysplastic cases, p53
      was detected, according to the immunostaining criteria, in one (16.7%) and four
      (66.7%) cases, respectively. CONCLUSIONS: In this group, p53 immunohistochemical
      expression, regardless of positive criteria take into account, was not useful for
      detecting dysplasia in Barrett's esophagus.

PMID- 16444380
TI  - [Common bile duct ligation as a model of hepatopulmonary syndrome and oxidative
      stress].
AB  - BACKGROUND: The hepatopulmonary syndrome is characterized by hepatic dysfunction
      and presence of dilated pulmonary vessels, with alterations in air diffusion that
      can be demonstrated in the experimental model of common bile duct ligation. AIM:
      To evaluate the oxidative stress in pulmonary tissue of cirrhotic rats with
      common bile duct ligation. MATERIAL/METHODS: We used 12 male Wistar rats weighing
      between 200-300 g divided in two groups: control (Co = 6) and cirrhotic (Ci = 6).
      We evaluated aminotransferases, arterial gasometry, lipoperoxidation and
      chemoluminescence), and antioxidant enzymatic activity with superoxide dismutase.
      The tissues analyzed for hepatopulmonary syndrome were cirrhotic liver and lung.
      RESULTS: The animals with common bile duct ligation showed alterations in the
      following aminotransferases: aspartate aminotransferase, Co = 105.3 +/- 43/Ci =
      500.5 +/- 90.3, alanine aminotransferase, Co = 78.75 +/- 37.7/Ci = 162.75 +/-
      35.4, and alkaline phosphatase, Co = 160 +/- 20.45/Ci = 373 +/- 45.44. The
      lipoperoxidation and the antioxidant response had significant differences between
      the groups when evaluated in lung (lipoperoxidation) Co = 0.87 +/- 0.3/Ci = 2.01
      +/- 0.9, chemoluminescence Co = 16008.41 +/- 1171.45/Ci = 20250.36 +/- 827.82
      superoxide dismutase Co = 6.66 +/- 1.34/Ci = 16.06 +/- 2.67. CONCLUSIONS: Our
      results suggest that in this experimental model of cirrhosis using common bile
      duct ligation, there is an increase in lipoperoxidation in pulmonary tissue as
      well as an increase in superoxide dismutase's antioxidant activity, suggesting a
      pulmonary injury caused by secondary biliary cirrhosis.

PMID- 16444381
TI  - Chloroquine for the maintenance of remission of autoimmune hepatitis: results of
      a pilot study.
AB  - BACKGROUND: Due to the risks related to long-term treatment with prednisone and
      azathioprine, most clinicians try to withdraw these drugs when patients with
      autoimmune hepatitis are in remission. However, there is a high probability of
      relapse, and most patients end up receiving maintenance treatment. AIM: To
      evaluate the safety and efficacy of maintenance treatment with chloroquine in the
      prevention of autoimmune hepatitis relapses. METHODS: Classical treatment was
      stopped after achievement of biochemical and histological remission of autoimmune
      hepatitis. Chloroquine diphosphate, 250 mg daily, was given for at least 12
      months or until the occurrence of relapses defined by levels of aminotransferases
      at least twice the upper normal values. RESULTS: Fourteen patients were
      consecutively treated and compared with 18 historical controls. There was a 6.49
      (1.38-30.30) greater chance of relapse in the historical controls when compared
      with patients treated with chloroquine (72.2% x 23.5%; 0.031). CONCLUSIONS: The
      group treated with chloroquine had a lower frequency of relapses. Chloroquine was
      safe in patients with autoimmune hepatitis and hepatic cirrhosis without
      decompensation, on 250 mg daily up to 2 years. These preliminary results provide
      a basis for upcoming controlled studies comparing chloroquine with placebo or for
      maintenance treatment with prednisone and/or azathioprine for the prevention of
      autoimmune hepatitis relapses.

PMID- 16444383
TI  - The huge burden of minor symptoms: the case of migraine headaches.

PMID- 16444382
TI  - Trimethoprim-sulfamethoxazole versus norfloxacin in the prophylaxis of
      spontaneous bacterial peritonitis in cirrhosis.
AB  - BACKGROUND: The prognosis of patients with chronic liver disease and spontaneous
      bacterial peritonitis is poor, being of great importance its prevention. AIM: To
      compare the effectiveness of trimethoprim-sulfamethoxazole versus norfloxacin for
      prevention of spontaneous bacterial peritonitis in patients with cirrhosis and
      ascites. PATIENTS AND METHODS: Fifty seven patients with cirrhosis and ascites
      were evaluated between March 1999 and March 2001. All of them had a previous
      episode of spontaneous bacterial peritonitis or had ascitic fluid protein
      concentration < or = 1 g/dL and/or serum bilirubin > or = 2.5 mg/dL. The patients
      were randomly assigned to receive either 800/160 mg/day of trimethoprim
      sulfamethoxazole 5 days a week or 400 mg of norfloxacin daily. The mean time of
      observation was 163 days for the norfloxacin group and 182 days for the
      trimethoprim-sulfamethoxazole group. In the statistical analysis, differences
      were considered significant at the level of 0.05. RESULTS: According to the
      inclusion criteria, 32 patients (56%) were treated with norfloxacin and 25 (44%)
      with trimethoprim-sulfamethoxazole. Spontaneous bacterial peritonitis occurred in
      three patients receiving norfloxacin (9.4%) and in four patients receiving
      trimethoprim-sulfamethoxazole (16.0%). Extraperitoneal infections occurred in 10
      patients receiving norfloxacin (31.3%) and in 6 patients receiving trimethoprim
      sulfamethoxazole (24.0%). Death occurred in seven patients (21.9%) who received
      norfloxacin and in five (20.0%) who received trimethoprim-sulfamethoxazole. Side
      effects occurred only in the trimethoprim-sulfamethoxazole group. CONCLUSION: In
      spite of the reduced number of patients and time of observation, trimethoprim
      sulfamethoxazole and norfloxacin were equally effective in spontaneous bacterial
      peritonitis prophylaxis, suggesting that trimethoprim-sulfamethoxazole is a valid
      alternative to norfloxacin.

PMID- 16444384
TI  - The role of serum and urinary urea in the evaluation of enteral protein intake in
      adequate and small-for-gestational-age very low birth weight infants.
AB  - CONTEXT AND OBJECTIVE: Very low birth weight (VLBW) infants have special
      nutritional needs. There is a current tendency to individualize their protein
      needs. The objective of this study was to determine the suitability of serum and
      urinary urea as indicators for protein intake in adequate-for-gestational-age
      (AGA) and small-for-gestational-age (SGA) VLBW infants. DESIGN AND SETTING:
      Prospective study in the nursery attached to the Maternity Ward of the "Prof.
      Pedro de Alcantara" Children's Institute, Hospital das Clinicas, Department of
      Pediatrics, Faculdade de Medicina da Universidade de Sao Paulo, Brazil. METHODS:
      Seventy-two VLBW infants (mean protein intake = 3.7 mg/kg/day) were enrolled in a
      prospective cohort study in two groups: AGA (n = 34) and SGA (n = 38). Blood
      samples, six-hour urine (6hUr) collections and urine sample tests (STUr) were
      obtained for urea and creatinine assays at three and five weeks of life.
      STATISTICAL ANALYSIS: Student's t test, Pearson correlation and linear regression
      (p < 0.05). RESULTS: There were no differences between groups for serum urea,
      6hUr and STUr, or between two assessments within each group. Serum urea
      correlated with 6hUr in both AGA and SGA, and to STUr in SGA; 6hUr correlated
      with STUr in both AGA and SGA. There was no correlation between protein intake
      and serum or urine urea. CONCLUSIONS: Serum and urinary urea did not reflect
      protein intake when mean intakes of 3.7 g/kg/day were used. Sample tests of
      urinary urea can be as reliable as urea from urine collected over longer periods.

PMID- 16444386
TI  - Fine-needle aspiration biopsy for breast lesions: a comparison between two
      devices for obtaining cytological samples.
AB  - CONTEXT AND OBJECTIVE: Fine-needle aspiration biopsy has been accepted worldwide
      for breast lesions. However, some questions remain, including the appropriateness
      of the puncture method. The objective of this work was to compare aspirates
      obtained by the auto-vacuum device and by the syringe pistol holder. DESIGN AND
      SETTING: Randomized trial for validation of diagnostic method, at Hospital das
      Clinicas da Universidade Federal de Goias and Hospital Araujo Jorge, Goiania.
      METHODS: 351 patients presenting breast lumps underwent fine-needle aspiration
      biopsy, either with the auto-vacuum device or the syringe pistol holder. A single
      cytopathologist analyzed all of the cytology slides. The rates of insufficient
      material, cellularity, cell distortion and background hemorrhage were evaluated.
      RESULTS: The percentages of insufficient material were 16% and 22% (p = 0.18),
      for the auto-vacuum and pistol aspirates, respectively. Good cellularity was seen
      in 34% of auto-vacuum and 29% of pistol samples (p = 0.4). Cell distortion was
      seen in 31 and 26 cases, respectively (p = 0.7). Background hemorrhage occurred
      in 63 (35%) and 54 cases (31%) (p = 0.2), for auto-vacuum and pistol. The
      sensitivity was 88% and 86%; specificity 99% and 100%, positive predictive value
      96% and 100%, negative predictive value 96% and 95% and total accuracy 76% and
      75% for the auto-vacuum and pistol, respectively. CONCLUSION: The results
      obtained from the two fine-needle aspiration biopsy methods were equivalent.
      Therefore, the auto-vacuum device is a good option for obtaining aspirates for
      cytology.

PMID- 16444385
TI  - Liposomal daunorubicin and dexamethasone as a treatment for multiple myeloma--the
      DD Protocol.
AB  - CONTEXT AND OBJECTIVE: Liposomal daunorubicin has been used to treat
      hematological malignancies, including multiple myeloma (MM). The goal was to
      evaluate efficacy, side-effects and toxicity of liposomal daunorubicin and
      dexamethasone ("DD Protocol"). DESIGN AND SETTING: Prospective study at Sirio
      Libanes, Sao Camilo, Brasil and Alemao Oswaldo Cruz hospitals. METHODS: Twenty
      consecutive patients with active MM received four cycles of liposomal
      daunorubicin intravenously for two hours (25-30 mg/m(2)/day) on three consecutive
      days per month, with oral dexamethasone (10 mg every six hours) on four
      consecutive days three times a month. RESULTS: The male/female ratio was 1:1 and
      median age 60. Nine patients were stage IIA, ten IIIA and one IIIB. The median
      from diagnosis to starting DD was 13 months. All patients received four cycles,
      except one. Fifteen had already received chemotherapy before DD. Responses of >
      50% reduction in serum monoclonal paraprotein were observed in six patients after
      first cycle (30%), six after second (30%) and four after third (20%), while four
      (20%) did not obtain this. Initially, 17 patients (85%) had anemia: 12 (70%)
      achieved correction. Progressive disease was observed in three patients (15%),
      while one had minimal response, four (20%) partial and 12 (60%) complete.
      Hematological toxicity was acceptable: three patients (15%) had neutrophils <
      1,000/mm(3); none had thrombocytopenia. Gastrointestinal toxicity was mild:
      nausea (10%), anorexia (15%) and no vomiting. CONCLUSIONS: This treatment has
      mild toxicity and good response rate. It may therefore be feasible before
      autologous bone marrow transplantation.

PMID- 16444387
TI  - High prevalence of malnutrition among patients with solid non-hematological
      tumors as found by using skinfold and circumference measurements.
AB  - CONTEXT AND OBJECTIVE: Malnutrition in cancer patients has many causes.
      Nutritional status is usually assessed from weight/height indices. These present
      limitations for the nutritional assessment of cancer patients: their weights
      include tumor mass, and lean mass changes are not reflected in weight/height
      indices. The objective was to evaluate differences between two anthropometric
      methods and compare deficits, in non-hematological tumor patients and
      hematological disease patients. DESIGN AND SETTING: Cross-sectional study at
      Instituto de Oncologia Pediatrica, Universidade Federal de Sao Paulo. METHODS:
      Children and adolescents were evaluated between March 1998 and January 2000.
      Traditional anthropometric measurements were obtained in the first month of
      treatment (induction therapy), by weight-for-height (W/H) using z-scores index
      for children and body mass index (BMI) for adolescents. Body composition
      evaluations consisted of specific anthropometric measurements: triceps skinfold
      thickness (TSFT), mid-upper arm circumference (MUAC) and arm muscle circumference
      (AMC). Data were analyzed to compare nutritional assessment methods for
      diagnosing malnutrition prevalence. The chi-squared test was used for comparative
      analyses between tumor patients and hematological disease patients. RESULTS:
      Analysis was done on 127 patients with complete data. Higher percentages of
      deficits were found among tumor patients, by W/H z-scores or BMI and by MUAC and
      AMC. Higher percentages of deficits were shown by TSFT (40.2%) and MUAC (35.4%)
      than by W/H z-scores or BMI (18.9%). CONCLUSION: Non-hematological tumor patients
      presented higher malnutrition prevalence than did hematological disease patients.
      Body composition measurements by TSFT and MUAC detected more patients with
      malnutrition than did W/H or BMI.

PMID- 16444388
TI  - Enzyme-linked immunosorbent assay (ELISA) immunoassaying versus microscopy:
      advantages and drawbacks for diagnosing giardiasis.
AB  - CONTEXT AND OBJECTIVE: Giardiasis is common in Brazil. For laboratory diagnosis,
      the method most utilized is microscopic examination of fecal samples, but the
      immunoenzymatic method is also available. The aim of this work was to verify the
      advantages and drawbacks of immunoassaying versus microscopy for diagnosing
      Giardia lamblia, when a single fecal sample is analyzed. DESIGN AND SETTING:
      Prospective, double-blind study at the parasitology laboratory of Faculdade de
      Medicina da Fundacao ABC. METHODS: Samples were prepared according to the
      traditional sedimentation (Hoffman, Pons and Janer) and Faust methods. Results
      were deemed positive when Giardia lamblia was found by one or both methods. The
      Prospect ELISA kit was used for detecting Giardia lamblia-specific antigen, in
      accordance with the manufacturer's instructions. Results were expressed on a
      visual scale as negative or positive (+, ++, +++ or ++++). RESULTS: The ELISA
      test was positive even when a significant proportion of corresponding samples
      examined by microscopy were negative. This trend was statistically significant (p
      < 0.001). The overall concordance of results between the ELISA test and
      microscopic examination of single samples was only moderate (0.50 by kappa test).
      CONCLUSION: The ELISA test is useful when just searching for Giardia lamblia,
      because of its high sensitivity. For daily practice, we recommend microscopy,
      which is much cheaper and can also detect other parasites. The low positivity of
      single samples in this method can be overcome by using three samples, as
      recommended by most authors.

PMID- 16444389
TI  - Pregnancy-associated venous thromboembolism in combined heterozygous factor V
      Leiden and prothrombin G20210A mutations.
AB  - CONTEXT: Pregnancy and puerperium raise the risk of thromboembolic events, and
      these risks are increased in women who are carriers of thrombophilia factors.
      Prothrombin (FII) G20210A and factor V Leiden heterozygous mutations are
      associated with moderate risk of thrombosis. The association of these
      thrombophilic conditions is very rare in pregnancy, and the real risk of
      thrombosis is unknown. CASE REPORT: We describe a case of a pregnant woman who
      was found to be carrier of heterozygous factor V Leiden and prothrombin (FII)
      G20210A mutations. Five years before pregnancy she had had an episode of
      extensive deep venous thrombosis in the ileofemoral region, while using hormonal
      contraceptives. Anticardiolipin antibody (ACA), lupus anticoagulant and
      deficiencies of protein C, protein S and antithrombin III were evaluated by means
      of enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time
      (dRVVT), coagulometric and chromogenic methods. Deoxyribonucleic acid (DNA) was
      amplified using the polymerase chain reaction (PCR) to study the factor V Leiden
      and G20210A mutations in the prothrombin gene and C677T mutation in the methylene
      tetrahydrofolate reductase (MTHFR) gene. In the sixth week of her first
      pregnancy, she developed another episode of deep venous thrombosis in the
      femoropopliteal veins of the right leg. She was treated with low-molecular weight
      heparin (nadroparin) until parturition (0.3 ml or 2,850 UI/day). The pregnancy
      evolved without any significant obstetric morbidity. The patient delivered a
      healthy baby by cesarean section. During the puerperium, she used prophylactic
      doses of nadroparin for (0.3 ml or 2,850 UI/day) six weeks and had no
      complications. We suggest that women who have an association of thrombophilia
      factors and a prior episode of venous thromboembolism must have antepartum
      anticoagulation management using unfractioned or low-molecular weight heparin and
      postpartum management using low-molecular weight heparin or oral anticoagulants.
      Anticoagulation is recommended during pregnancy because the real magnitude of the
      risk of major and life-threatening thromboembolic events in these women is
      unknown.

PMID- 16444390
TI  - Purtscher-like retinopathy associated with acute pancreatitis.
AB  - CONTEXT: Purtscher-like retinopathy with bilateral loss of vision is a rare and
      severe complication that may follow acute pancreatitis. CASE REPORT: The case of
      a 35-year-old patient with acute alcoholic pancreatitis who developed sudden loss
      of visual acuity is described. The ophthalmoscopic examination revealed diffuse
      retinal whitening of the posterior pole with confluent cotton-wool spots.
      Fluorescein angiogram showed retinal arteriolar occlusion. The findings were
      compatible with Purtscher-like retinopathy. Computed tomography of the abdomen
      demonstrated enlarged liver and pancreas with edema and inflammation. The
      pathogenesis of this form of retinopathy still remains uncertain and there is no
      specific treatment available.

PMID- 16444391
TI  - A familial case of cleidocranial dysostosis presenting upper limb ischemia.
AB  - CONTEXT: Upper limb ischemia is not as common as lower limb ischemia but may
      cause severe impairment or disability if it is misdiagnosed. CASE REPORT: A case
      of a woman with cleidocranial dysostosis resulting in upper right limb ischemia
      is presented. This uncommon condition is an exceedingly rare cause of vascular
      compression that gives rise to thrombosis of the axillary-subclavian arteries.
      Only two cases have previously been reported.

PMID- 16444392
TI  - Pattern of prolactin secretion after administration of gonadotropin-releasing
      hormone agonist at the preovulatory phase of intrauterine insemination cycles.
AB  - CONTEXT AND OBJECTIVE: Administration of a gonadotropin-releasing hormone (GnRH)
      agonist at the preovulatory phase is an option for triggering ovulation in
      assisted reproductive technology cycles. The aim of this work was to investigate
      the pattern of prolactin secretion after the administration of a single dose of
      GnRH-agonist at the preovulatory phase. DESIGN AND SETTING: Descriptive study at
      a tertiary referral center. PARTICIPANTS: Fifteen normally ovulating patients
      undergoing ovarian stimulation for intrauterine insemination were studied.
      METHODS: Ovarian stimulation was carried out using human menopausal gonadotropin
      (intramuscular 75 IU daily). When at least one follicle reached 17 mm (observed
      echographically), 0.5 mg of buserelin acetate was administered. Blood samples
      were taken to determine prolactin concentrations, at the time of agonist
      injection and 4, 8, 12, 24 and 48 hours later. RESULTS: A statistically
      significant increase in serum levels of prolactin was observed 4, 8 and 12 hours
      after GnRH-agonist administration, with a peak at 8 hours. CONCLUSION: The
      administration of a single dose of GnRH-agonist at the preovulatory phase in
      patients undergoing ovarian stimulation performed with human menopausal
      gonadotropin causes a significant increase in serum prolactin levels.

PMID- 16444393
TI  - Preliminary results from minimally invasive video-assisted thyroidectomy.
AB  - CONTEXT AND OBJECTIVE: Minimally invasive video-assisted gasless thyroidectomy
      (MIVAT) has mainly been described in Italy and has been demonstrated to be a safe
      procedure with additional advantages regarding cosmetic results and postoperative
      outcome. The aim of this work is to analyze our preliminary results from
      minimally invasive video-assisted thyroidectomy. DESIGN AND SETTING:
      Retrospective study at the Head and Neck Surgery Service of Hospital Ana Costa,
      Santos. METHODS: Twelve patients underwent hemithyroidectomy and another three
      underwent total thyroidectomy by means of minimally invasive video-assisted
      thyroidectomy between June and September 2004. Gender, age, goiter volume, major
      diameter of the dominant nodule, duration of surgery, pain complaints during the
      first postoperative day, length of hospital stay, cosmetic result and
      complications were retrospectively analyzed. RESULTS: All the patients were
      women, with median age of 34. The median goiter volume was 16.5 ml, and the
      median major diameter of the nodule was 2.3 cm. Ten patients reported mild pain
      at the surgical site. The median scar size was 2.0 cm and all patients considered
      the cosmetic results excellent. The median duration of surgery was 55 minutes,
      all patients were discharged on the first postoperative day, and there were no
      complications. CONCLUSIONS: The outcome from minimally invasive video-assisted
      thyroidectomy is good in terms of cosmetic results, analgesia and postoperative
      recovery. The scar is shorter than in the conventional procedure.

PMID- 16444395
TI  - Nursing research in Latin America: 1988-1998.
AB  - The purpose of this article is to provide an overview of nursing research in
      Latin America during the decade from 1988 to 1998. Data from the bi-annual Pan
      American Colloquia in Nursing Research from 1988 to 1998 were subject to
      secondary analysis. Findings indicate that most of the research emanated from
      Brazil, the only country with a doctoral program in nursing in the 1990's.
      Research topics included: public health issues, clinical studies (usually of
      adults), nursing care studies of process, therapeutic communication, and
      administrative issues such as standards of care and quality. The most common
      design was descriptive quantitative, although there were several qualitative
      studies. The analysis provides directions for future research and indicates areas
      of concern, especially the need for theory based nursing research.

PMID- 16444396
TI  - [Significance of teaching the Nursing Process for the faculty].
AB  - This paper aimed to analyze the significance of teaching the Nursing Process (NP)
      for faculty, through the Representational Theory of Significance. Ten professors
      from Guanajuato University participated in the investigation. Data were collected
      through semi-structured interview and questionnaire. The analysis was done from
      the perspective of the mentioned theory. All faculty members know, teach and
      apply the NP. They also refer to the importance of its teaching and practice by
      professionals. In conclusion, regarding the significance of the nursing process,
      faculty members tend to recognize it as a scientific method and an important
      instrument in professional nursing activities; as for the meaning of teaching the
      nursing process, it is considered as a well-founded, indispensable and modern
      instruction for the discipline, as long as it covers the five stages it consists
      of.

PMID- 16444397
TI  - [Nursing care planning: proposal for a software prototype].
AB  - This study aims to develop a software prototype to help hospital nurses plan
      nursing care, and carry out nursing interventions and all documentation in a
      computerized way. The methodology is based on the life cycle of system
      development, particularly the prototype concept, involving two phases: definition
      and development. The definition phase began with the planning stage, followed by
      the definition and analysis of requirements for the construction, and culminated
      with the specification of the software requirements. The development phase
      translated the group of requirements into a computerized model, structured in 10
      modules, regarding the nursing care system process. The performance of this
      innovative resource in the different stages of the nursing care system process
      will be analyzed in future studies.

PMID- 16444398
TI  - [Patients' coping strategies during radiotherapy].
AB  - Cancer is a disease that entails inquiries and a wide range of problems for
      persons going through this experience, inevitably leading to stress, which is
      part of human life. There are different ways of adapting to a situation to cope
      with the stress. What makes a difference in this context are the coping
      strategies, defined as a process used to control the demands of the relationship
      between individual and environment, to be elaborated by the individual. In this
      study, we tried to identify the forms used to cope with the disease and
      treatment. This is a qualitative study, using Collective Subject Discourse
      Analysis and the theoretical framework of coping. Sixteen radiotherapy patients
      were interviewed as part of a convenience sample. When faced with cancer and
      radiotherapy, the patients elaborated coping strategies that were based on
      emotion as well as on the problem.

PMID- 16444399
TI  - [The act of taking care in the dying process from the perspective of women with
      cancer: a phenomenological attitude].
AB  - The trajectory of this study was focused on understanding the meaning of taking
      care of women with cancer, without any possibilities of cure, through their
      perspective. With this proposal, we chose to carry out a qualitative survey,
      according to a phenomenological approach, based on these directive questions:
      "Tell me how I can take care of you. How would you like to be taken care of?" The
      descriptions evidenced the ontological unifications that were analyzed and
      interpreted according to Martin Heidegger's reference framework. These
      unifications made it possible to reveal ways for the act of taking care in the
      dying process that go beyond technical-scientific knowledge, because taking care
      also involves empathy, listening, patience, zeal, pain control and autonomy.
      Based on these women's point of view, we could reach the sense of being a person
      with cancer in the dying process, not as something finished, but as a person with
      possibilities, in spite of facing the factual situation of living with the
      existential end.

PMID- 16444401
TI  - [Information received by parents during children's hospitalization].
AB  - This study aimed to find out how parents perceive the information they received
      from nurses during the hospital stay of their children and identify what
      information nurses indicate they supply to the parents. We carried out a
      descriptive-exploratory study with a quantitative approach at the pediatric
      internment units of a teaching hospital in the city of Sao Paulo, interviewing 50
      parents whose children were hospitalized and 12 nurses working at these units.
      The results showed that parents were not completely satisfied with the
      information received from the nurses during the children's stay in hospital. The
      nurses mainly provided information to the parents about rules and routines,
      rights and obligations, reasons for procedures and parents' participation in care
      for the child. Parents asked the nurses information about the duration of their
      child;s hospitalization, progression of the disease, medication and treatment.

PMID- 16444400
TI  - [Humanized birth according to obstetric nurses involved in birth care].
AB  - This qualitative study aimed at identifying how obstetrical nurses perceive the
      humanization of delivery care, as well as evidencing, based on their discourse,
      the actions they develop during the birth process and factors that complicate the
      implementation of this care. Study participants were 16 nurses from a maternity
      in the interior of Sao Paulo, Brazil. Following the Collective Subject Discourse
      framework, data were collected by using semistructured interviews that were
      recorded, transcribed and organized for tabulation and analysis. The results show
      that, according to these nurses, the humanization process happened as a political
      strategy for improving care and rescuing normal birth. They believe there is a
      need to change the paradigm for the process to be concretized. These results also
      showed that nurses are more integrated with humanized birth as a process, and not
      as an event.

PMID- 16444402
TI  - [Trying to maintain the equilibrium to serve their demands and take care of
      hospitalized children: the family experience].
AB  - The purposes of this qualitative study were to understand the meaning of the
      interactions experienced by the family during a child's hospitalization, identify
      the family's demands and construct a theoretical model representing this
      experience. Symbolic Interactionism was adopted as a theoretical and Grounded
      Theory as a methodological reference framework. Data were collected by means of
      observation and interviews with five families of children hospitalized due to
      acute disease with a good prognosis. The analysis identified two interactive
      phenomena: losing control of the functioning, which expresses the situations
      experienced by the families, which generate demands; and seeking a new
      functioning rhythm, which shows the strategies the family undertakes to take care
      of the hospitalized child and maintain its functioning. The identification of the
      central category and the construction of the Theoretical Model represent the
      meaning of the experience for families during the hospitalization of one of their
      children.

PMID- 16444403
TI  - [Family vulnerability: concept development].
AB  - This study aimed to develop the concept of family vulnerability. Data were
      collected through Qualitative Concept Analysis, which involves two phases. In the
      first, theoretical phase, data from literature were used for identification of
      the theoretical attributes of the concept. In the second, field phase, data were
      collected by means of observations and interviews with twelve families going
      through the experience of a child's disease and hospitalization. Symbolic
      Interactionism was used as a theoretical framework, which supported Grounded
      Theory, applied to guide data collection and analysis in the field phase. As a
      result of phase II, a theoretical model was built, whose central category defines
      family vulnerability as FEELING THREATENED IN THEIR AUTONOMY, due to the
      interactions between family members, illness and health team. The comparison
      between the two analyses allowed for a theoretical proposition of family
      vulnerability and advances in terms of theoretical knowledge on family nursing.

PMID- 16444404
TI  - [Family and eating disorders: representations among nursing staff at a mental
      health university hospital].
AB  - This qualitative and descriptive study takes the family of patients with eating
      disorders as a starting point. We aimed to contextualize this theme and
      apprehend, from the reports of interviewed professionals, their representations
      about the family of these patients and its influence on the genesis and
      development of the illness. Data showed that, at first, the family is represented
      as a primary social group which is always expecting certain behaviors and which,
      as a formative element, participates in the origin of the disorder. Subsequently,
      the family theme appears to be more directed to understanding the family as an
      element that maintains the eating disorder, in which the not very defined limits
      among its members disturb the relationship, often evidencing an alteration in the
      hierarchy: the parents start to be controlled by their child.

PMID- 16444405
TI  - [Repercussion of child malnutrition in the family].
AB  - Children's nutritional condition reflects both their food consumption and health
      condition. These factors depend on the food available at home, salubriousness,
      the environment and the care the child receives. This qualitative study presents
      perceptions and feelings in order to understand how families live with the
      problem of child malnutrition. Data were collected through semistructured
      interviews and observations, involving 10 mothers of undernourished children in
      the suburbs of Fortaleza-Ceara, Brazil. The transcriptions of their discourse
      revealed the theme categories unemployment and food insecurity. The synthesis of
      the categories under analysis evidenced that the hunger problem is characteristic
      by the family's insecurity. Thus, they search for support options, such as health
      centers, relatives, church and community. There is a need to prioritize
      preventive work, through public health policies, aimed at measures related to the
      real world of health promotion.

PMID- 16444406
TI  - [Home Care--configurating the care model and joining different interests/needs in
      the care sector].
AB  - This study aims to analyze a private Home Care service from the perspective of
      the formation of the Care Model. Focus groups and semistructured interviews were
      chosen as instruments for data collection. Interviews were held among middle
      level nursing workers and service coordinators. Empiric data were organized by
      means of the Collective Subject Discourse methodology. It was disclosed that the
      recognition of the constituent elements of the care model among the social agents
      involved in the project is essential to negotiate, unite and instrumentalize the
      possibility to attend different interests. Another factor that stood out was the
      power of Home Care to be a tool for reviewing the health/illness/care process
      concept and, thus, for promoting the incorporation of values that lead to
      behavioral changes, moving towards a care model that is committed to the
      establishment of a welcoming relation, characterized by commitment and
      responsibility for the health of clients.

PMID- 16444407
TI  - [The professional self and hetero image among public health nurses: a study of
      social representations].
AB  - The object of this study is the professional image constructed by public health
      nurses and the objective is to describe and analyze the professional images
      present in the representations of nurses who deliver direct care to this
      clientele. The theoretical-methodological reference framework adopted was Social
      Representations Theory. A qualitative study was developed in Petropolis-Rio de
      Janeiro/Brazil, through in-depth interviews with 30 nurses. Alceste 4.5 software
      was used for the lexical analysis. The results reveal the existence of a
      professional self-image with three groups of meanings: being a reference for the
      team, the non-specific image and the image of plaster; and a professional hetero
      image with four groups of meanings: administrator, invisible, positive image and
      superposition. The study of the professional image reflects the construction of
      the nurse's identity in itself and emphasizes Social Representations Theory as a
      useful tool for nursing research development.

PMID- 16444408
TI  - [The nurse as an action tool in care for the aged].
AB  - This study approaches nursing care as related to the aged. The studied situation
      involved health care needs of hospitalized persons, using the following central
      question: which is the meaning of nurses' actions when attending hospitalized
      aged patients without expectation of recovery and when technology is no longer
      that important? We aimed to reflect about hospitalized elders' needs in nursing
      reality. Comprehensive Sociology was used as a theoretical-methodological
      framework. The study was carried out at an Intensive Care Service of a Municipal
      Hospital in the city of Rio de Janeiro-Brazil. The subjects were nurses who
      attend hospitalized aged persons without any expectation of recovery, who were
      approached through a phenomenological interview. Through a comprehensive
      analysis, we identified care by being together, providing at the same time
      physical comfort and well-being to cope with the situation as typical of nursing
      actions. This study indicates some contributions for nursing care, assistance,
      teaching and research, aimed at strengthening nurses' attitude as an action tool
      in care for aged patients.

PMID- 16444409
TI  - [Family Health Program: the construction of a new care model].
AB  - The Family Health Program (FHP) arises as a new strategy for health care and
      reorganization of the care model. Based on these presuppositions, this article
      aims to reflect on the potentialities and contradictions of the FHP in the care
      model change process. The study adopts a descriptive-reflexive methodology and
      presents two themes, based on literature: historical revision of health policies
      in Brazil and FHP and the care model change process. The analysis made it
      possible to perceive work in teams and with families as a progress in the FHP.
      However, there is a need for a broader perspective in the formation of
      professionals to work with the new proposal, as well as to implant the teams.

PMID- 16444410
TI  - Moving in the right direction: first step in writing for publication in nursing.
AB  - Current trends suggest that the dissemination of nursing knowledge and published
      papers in high quality journals bring further development in the
      professionalization of nursing. There is limited understanding of the factors
      that enable nurses' writing for publication, but an educational programme on
      publications skills development at all levels of nursing could act as a catalyst
      in this process of change. Nursing leaderships not only account for the
      responsibility to contribute to the nursing knowledge base through publications,
      but also to prepare future nurses in the same arena. The aims of the paper are to
      examine some issues regarding nursing publications, postgraduate nurses in
      particular, and suggest book reviews as a framework for the professional
      development of nurses in how to write for publication.

PMID- 16444411
TI  - Lutzomyia longipalpis and the eco-epidemiology of American visceral
      leishmaniasis, with particular reference to Brazil: a review.
AB  - An historical review is given of American visceral leishmaniasis (AVL), with
      particular reference to the eco-epidemiology of the disease in Brazil. Following
      the first records of AVL in this country, in 1934, the sandfly Lutzomyia
      longipalpis (Lutz and Neiva, 1912) was incriminated as the principal vector. It
      is now generally accepted, however, that there exist a number of cryptic species
      under the name of Lu. longipalpis s.l. and that variations in the quantity of the
      vasodilatory peptide maxadilan in the saliva of flies from different populations
      of Lu. longipalpis s.l., may account for the variable clinical manifestations of
      AVL seen in different geographic regions. Distribution of AVL has been shown to
      extend throughout most of South and Central America, with the domestic dog
      serving as the principal reservoir of infection for man. However, while one
      hypothesis suggests that the causative parasite is Leishmania infantum, imported
      from Europe with the Portuguese and Spanish colonists, the demonstration of a
      high rate of benign, inapparent infection in foxes in Amazonian Brazil raised an
      opposing suggestion that the parasite is indigenous to the Americas. Recent
      reports of similar infections in native marsupials, and possibly rodents, tend to
      support this view, particularly as Lu. longipalpis is primordially a silvatic
      sandfly. Although effective control measures in foci of the disease will diminish
      the number of canine and human infections, the presence of such an enzootic in a
      variety of native animals will render the total eradication of AVL unlikely.

PMID- 16444412
TI  - Ticks, ivermectin, and experimental Chagas disease.
AB  - Following an infestation of dogticks in kennels housing dogs used for long-term
      studies of the pathogenesis of Chagas disease, we examined the effect of
      ivermectin treatment on the dogs, ticks, trypanosome parasites, and also on
      triatomine vectors of Chagas disease. Ivermectin treatment was highly effective
      in eliminating the ticks, but showed no apparent effect on the dogs nor on their
      trypanosome infection. Triatominae fed on the dogs soon after ivermectin
      treatment showed high mortality, but this effect quickly declined for bugs fed at
      successive intervals after treatment. In conclusion, although ivermectin
      treatment may have a transient effect on peridomestic populations of Triatominae,
      it is not the treatment of choice for this situation. The study also showed that
      although the dogticks could become infected with Trypanosoma cruzi, this only
      occurred when feeding on dogs in the acute phase of infection, and there was no
      evidence of subsequent parasite development in the ticks.

PMID- 16444413
TI  - Detection of dengue virus serotype 3 by reverse transcription-polymerase chain
      reaction in Aedes aegypti (Diptera, Culicidae) captured in Manaus, Amazonas.
AB  - The detection of dengue virus serotypes from Aedes aegypti in Manaus, state of
      Amazonas was carried out using the reverse transcription-polymerase chain
      reaction technique. Fourteen pools out 82 (17.1%) were positive for DENV3,
      providing a minimal infection rate of 2.1% of all analyzed infected female
      specimens of three different areas of the city.

PMID- 16444414
TI  - Detection of Rickettsia rickettsii in the tick Amblyomma cajennense in a new
      Brazilian spotted fever-endemic area in the state of Minas Gerais.
AB  - The present study evaluated rickettsial infection in Amblyomma spp. ticks
      collected in a farm in Coronel Pacheco, a Brazilian spotted fever (BSF) endemic
      area. A total of 78 A. cajennense and 78 A. dubitatum free-living adult ticks
      were collected and tested by polymerase chain reaction (PCR) targeting a fragment
      of the rickettsial gene gltA. Only one pool of three A. cajennense ticks showed
      the expected product by PCR. This pool was further tested by PCR using sets of
      primers targeting the rickettsial genes gltA, ompA, and ompB. All reactions
      yielded the expected bands that by sequencing, showed 100% identity to the
      corresponding sequences of the Rickettsia rickettsii gene fragments gltA (1063
      bp), ompA (457-bp), and ompB (720-bp). The minimal infection rate of R. rickettii
      in the A. cajennense population was 1.28% (at least one infected tick within 78
      ticks). The present study showed molecular evidence for the presence of R.
      rickettsii in A. cajennense from a BSF-endemic area in Coronel Pacheco, state of
      Minas Gerais. Although R. rickettsii has been previously reported infecting A.
      cajennense ticks in Brazil and other Latin American countries, the present study
      performed the first molecular characterization of R. rickettsii from the tick A.
      cajennense.

PMID- 16444415
TI  - Parvovirus B19 infections in state of Rio de Janeiro, Brazil: 526 sera analyzed
      by IgM-enzyme-linked immunosorbent assay and polymerase chain reaction.
AB  - In this study were analyzed 526 sera; the patients aged from two days to 65 years
      old presenting exanthema, which was the most frequent symptom observed, besides
      fever, adenomegaly, and arthralgia. These sera were negative by enzyme-linked
      immunosorbent assay (IgM-ELISA) for either rubella (495), toxoplasma (41),
      cytomegalovirus (12), measles (40), dengue (56), and they were submitted to
      nested polymerase chain reaction (PCR) for B19 DNA and commercial IgM-ELISA for
      B19. In 39 abortion cases, IgM or DNA were not detected, therefore they were not
      took into account for analysis. Specific DNA and IgM were detected respectively
      in 71 (14.5%) and IgM in 62 (12.7%) sera from 487 sera analyzed. IgM and DNA were
      simultaneously detected in 43 (8.8%), while agreement among the results by PCR
      and IgM-ELISA was observed in 440 (90.4%). The sera were collected from January
      1999 to December 2000, most of them in 1999 (325), during winter and spring. The
      major number of clinical cases was observed in the age group from one to ten
      years old. IgM or DNA were detected in 23 from 51 municipal districts of the
      state of Rio de Janeiro, where the samples were collected.

PMID- 16444416
TI  - Antibodies to Rickettsia rickettsii, Rickettsia typhi, Coxiella burnetii,
      Bartonella henselae, Bartonella quintana, and Ehrlichia chaffeensis among healthy
      population in Minas Gerais, Brazil.
AB  - Rickettsial diseases except those belonging to spotted fever group rickettsioses
      are poorly studied in South America particularly in Brazil where few
      epidemiological reports have been published. We describe a serosurvey for
      Rickettsia rickettsii, R. typhi, Coxiella burnetii, Bartonella henselae, B.
      quintana, and Ehrlichia chaffeensis in 437 healthy people from a Brazilian rural
      community. The serum samples were tested by indirected micro-immunoflourescence
      technique and a cutoff titer of 1:64 was used. The seroprevalence rates for R.
      rickettsii, R. typhi, C. burnetii, B. henselae, B. quintana, and E. chaffeensis
      were respectively 1.6% (7 samples); 1.1% (5 samples); 3.9% (17 samples); 13.7%
      (60 samples); 12.8% (56 samples), and 10.5% (46 samples). Frequent multiple/cross
      reactivity was observed in this study. Age over 40 years old, urban profession,
      and rural residence were significantly associated with some but not all
      infections rate. Low seropositivity rates for R. rickettsii, R. typhi, and C.
      burnetii contrasted with higher rates of seropositivity for B. quintana, B.
      henselae, and E. chaffeensis. These results show that all tested rickettsial
      species or antigenically closely related possible exist in this particular
      region.

PMID- 16444417
TI  - Shared and non-shared antigens from three different extracts of the metacestode
      of Echinococcus granulosus.
AB  - Hydatid cyst fluid (HCF), somatic antigens (S-Ag) and excretory-secretory
      products (ES-Ag) of Echinococcus granulosus protoscoleces are used as the main
      antigenic sources for immunodiagnosis of human and dog echinococcosis. In order
      to determine their non-shared as well as their shared antigenic components, these
      extracts were studied by ELISA-inhibition and immunoblot-inhibition. Assays were
      carried out using homologous rabbit polyclonal antisera, human sera from
      individuals with surgically confirmed hydatidosis, and sera from dogs naturally
      infected with E. granulosus. High levels of cross-reactivity were observed for
      all antigenic extracts, but especially for ES-Ag and S-Ag. Canine antibodies
      evidenced lesser avidity for their specific antigens than antibodies from human
      origin. The major antigenic components shared by HCF, S-Ag, and ES-Ag have
      apparent molecular masses of 4-6, 20-24, 52, 80, and 100-104 kDa, including
      doublets of 41/45, 54/57, and 65/68 kDa. Non-shared polypeptides of each
      antigenic extract of E. granulosus were identified, having apparent masses of 108
      and 78 kDa for HCF, of 124, 94, 83, and 75 kDa for S-Ag, and of 89, 66, 42, 39,
      37, and 35 kDa for ES-Ag.

PMID- 16444418
TI  - A genotyping study of human immunodeficiency virus type-1 drug resistance in a
      small Brazilian municipality.
AB  - In Brazil, surveillance studies on antiretroviral drug resistance among drug
      naive and treatment-experienced patients have focused primarily on patients
      living in large urban centers. As the epidemic spreads towards small
      municipalities and the innermost parts of the country, it will be essential to
      monitor the prevalence of antiretroviral drug resistance in these areas. We
      report the first survey on the prevalence of antiretroviral drug resistance in a
      small Brazilian municipality. Between July 1999 and March 2005, 72 adult human
      immunodeficiency virus type-1(HIV-1)-infected patients received care at the
      Municipal HIV/AIDS Program of the small, southeastern municipality of Miracema,
      state of Rio de Janeiro. A genotyping study of antiretroviral drug resistance was
      performed in 54 patients. Among 27 samples from treatment-experienced patients, 9
      (33.3%) harbored strains with reduced drug susceptibility. Among these, 6 had
      reduced susceptibility to reverse transcriptase (RT) inhibitors and 3 to both RT
      and protease inhibitors. No primary antiretroviral drug resistance was recorded
      among 27 drug-naive subjects. The relatively low prevalence of resistance
      mutations in the Miracema cohort argues against the concern that resource-poor
      settings should not implement widespread accessibility to standard of care
      antiretroviral combinations due to the possibility of sub-optimal adherence
      leading to the emergence and spread of drug-resistant strains.

PMID- 16444419
TI  - Clinical and pathological importance of vacA allele heterogeneity and cagA status
      in peptic ulcer disease in patients from North Brazil.
AB  - We have examined the prevalence of gene cagA and vacA alleles in 129 patients, 69
      with gastritis and 60 with peptic ulcer diseases from North Brazil and their
      relation with histopathological data. vacA and cagA genotype were determined by
      polymerase chain reaction. Hematoxylin-eosin staining was used for histological
      diagnosis. 96.6% of the patients were colonized by Helicobacter pylori strains
      harboring single vacA genotype (nont-mixed infection). Among them, 11.8% had
      subtype s1a, 67.8% had subtype s1b, and 17% subtype s2. In regard to the middle
      region analysis, m1 alleles were found in 75.4% and m2 in 21.2% of patients. The
      cagA gene was detected in 78% patients infected with H. pylori and was associated
      with the s1-m1 vacA genotype. The H. pylori strains, vacA s1b m1/cagA-positive,
      were associated with increased risk of peptic ulcer disease and higher amounts of
      lymphocytic and neutrophilic infiltrates and the presence of intestinal
      metaplasia. These findings show that cagA and vacA genotyping may have clinical
      relevance in Brazil.

PMID- 16444420
TI  - Evaluation of the natural killer cytotoxicity and the levels of cytokines in rats
      with type I diabetes mellitus.
AB  - Type I diabetes mellitus (insulin-dependent DM = IDDM) is a chronic disease
      characterized by specific destruction of pancreatic beta cells, resulting in an
      absolute lack of insulin. Immune mechanisms, genetic susceptibility, and
      environmental factors are all implicated in the pathogenesis of Type 1 diabetes.
      This study was aimed at determining the efficiency of cytokines, natural killer
      (NK) cells in the pathophysiology of IDDM. Therefore, we evaluated the plasma
      levels of cytokines by specific enzyme-linked immunosorbent assay (ELISA) and the
      cytotoxicity activity of NK cells by anti-candididal index in rats with type I
      diabetes. We found that the cytotoxicity activity of NK cells in IDDM groups
      significantly decreased compared to the control groups. The levels of interferon
      gamma (IFN-gamma) in IDDM groups were slightly higher than in healthy controls.
      These results indicate that the changes of T H1 type cytokines such as IFN-gamma
      and NK cell activity can play a role in the etiology of IDDM. The data may
      provide new strategies for the treatment of IDDM.

PMID- 16444421
TI  - Studies in a co-infection murine model of Plasmodium chabaudi chabaudi and
      Leishmania infantum: interferon-gamma and interleukin-4 mRNA expression.
AB  - This work aimed to study the T helper type 1/2 (Th1/Th2) cytokine profile in a co
      infection murine model of Plasmodium chabaudi chabaudi and Leishmania infantum.
      Expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was analyzed,
      in spleen and liver of C57BL/6 mice, by reverse transcriptase-polymerase chain
      reaction. High levels of IFN-gamma expression did not prevent the progression of
      Leishmania in co-infected mice and Leishmania infection did not interfere with
      the Th1/Th2 switch necessary for Plasmodium control. The presence of IL-4 at day
      28 in co-infected mice, essential for Plasmodium elimination, was probably a key
      factor on the exacerbation of the Leishmania infection.

PMID- 16444422
TI  - Effect of food on immature development, consumption rate, and relative growth
      rate of Toxorhynchites splendens (Diptera: Culicidae), a predator of container
      breeding mosquitoes.
AB  - Food utilization by the larvae of Toxorhynchites splendens (Wiedemann) was
      studied in the laboratory by offering larvae of Aedes aegypti Linnaeus, Anopheles
      stephensi (Liston), and Culex quinquefasciatus (Say). Quantitative analyses of
      data indicated that immature development was significantly faster with increase
      in food availability. The regression analysis showed that the degrees of the
      relationship between immature duration (Id) and food availability were higher
      when offered early instars of prey (first and second instars) than late instars.
      Consumption rate (Cr) of the predator increased with increase in food
      availability and this relationship was highly significant when larvae of An.
      stephensi were offered as food. Consumption rate to food level decreased with
      increase in the age class of the prey. There was a significant negative
      correlation between Id and Cr. This aspect helps to increase population turnover
      of T. splendens in a shorter period when the prey is abundant. Conversely, the
      predator compensated the loss in daily food intake at low food level by extending
      Id thereby attains the minimum threshold pupal weight for adult emergence. There
      was an increase in the relative growth rate (RGR) of the predator when An.
      stephensi was offered as prey and this was related to the high protein content of
      the prey per body weight. There was a positive correlation between Cr and RGR.
      This adaptive life characteristic strategy of this predator is useful for mass
      rearing for large scale field release programmes in the control of container
      breeding mosquitoes is discussed.

PMID- 16444423
TI  - Basic biology of Pneumocystis carinii: a mini review.
AB  - Basic aspects of cell biology of Pneumocystis carinii are reviewed with major
      emphasis on its life cycle and the structural organization of the trophozoites
      and cyst forms. Initially considered as a protozoan it is now established that
      Pneumocystis belongs to the Fungi Kingdom. Its life cycle includes two basic
      forms: (a) trophozoites, which are haploid cells that divide by binary fission
      and may conjugate with each other forming an early procyst and (b) cysts where
      division takes place through a meiotic process with the formation of eight nuclei
      followed by cytoplasmic delimitation and formation of intracystic bodies which
      are subsequently released and transformed into trophozoites. Basic aspects of the
      structure of the two developmental stages of P. carinii are reviewed.

PMID- 16444424
TI  - Analysis of antenal sensilla patterns of Rhodnius prolixus from Colombia and
      Venezuela.
AB  - Antennal sensilla patterns were used to analyze population variation of domestic
      Rhodnius prolixus from six departments and states representing three
      biogeographical regions of Colombia and Venezuela. Discriminant analysis of the
      patterns of mechanoreceptors and of three types of chemoreceptors on the pedicel
      and flagellar segments showed clear differentiation between R. prolixus
      populations east and west of the Andean Cordillera. The distribution of thick and
      thin-walled trichoids on the second flagellar segment also showed correlation
      with latitude, but this was not seen in the patterns of other sensilla. The
      results of the sensilla patterns appear to be reflecting biogeographic features
      or population isolation rather than characters associated with different habitats
      and lend support to the idea that domestic R. prolixus originated in the eastern
      region of the Andes.

PMID- 16444425
TI  - Morphobiological aspects of Rhodnius brethesi Matta, 1919 (Hemiptera:Reduviidae)
      from the Upper and Middle Negro River, Amazon region of Brazil: I - scanning
      electron microscopy.
AB  - The occurrence of autochthonous cases of Chagas disease in the Amazon region of
      Brazil over recent decades has motivated an intensification of studies in this
      area. Different species of triatomines have been identified, and ten of these
      have be proven to be carriers of the parasite Trypanosoma cruzi or " cruzi-like "
      parasites. Studies conducted in the municipalities of Santa Isabel do Rio Negro
      and Barcelos, located on the Upper and Middle of the Negro River, microregion of
      Negro River, state of Amazonas have confirmed not only that Rhodnius brethesi is
      present in the palm tree Leopoldinia piassaba, but also that this insect was
      recognized by palm fiber collectors. A morphological study of eyes, inter-ocular
      and inter-ocellar regions, antennae, buccula, labrum, rostrum, stridulatory
      sulcus and feet, including the apex of the tibia, spongy fossette and ctenidium
      was conducted by scanning electron microscopy. The buccula and the stridulatory
      sulcus presented notable differences in specimens of different genera and also of
      different species. These data make it possible to suggest that the details
      presented in these structures can be included as diagnostic characteristics to be
      used in new dichotomous keys, thereby contributing towards studies of taxonomy
      and systematics and furnishing backing for comparative analysis of specimens
      collected from different localities.

PMID- 16444426
TI  - Candida colonization in intensive care unit patients' urine.
AB  - The objective of this study was to identify possible predisposing factors for
      candiduria in intensive care unit (ICU) patients from Hospital das Clinicas,
      Universidade Federal de Goias, Goiania, Brazil, during one year. Urine samples
      from 153 ICU patients were obtained by catheterization on admission day and every
      seven days. Data such as sex, age, antifungal therapy, and variables as
      antibiotics, underlying diseases or comorbid conditions and stay in the hospital,
      were collected from patients who had at least one urine culture that yielded >
      10(3) yeast colonies/ml. Candiduria was recovered in 68 patients and the
      commonest predisposing factors were antibiotic therapy (100%) and indwelling
      urinary catheter (92.6%). The percentage of Candida spp. isolation increased
      during the extended periods in which patients remained in the ICU. C. albicans
      was isolated in 69.1%, and the other species non-albicans as C. glabrata, C.
      kefyr, C. parapsilosis, C. famata, C. guilliermondii, C. krusei, and C.
      tropicalis were isolated in lower percentage. The high frequency of candiduria
      and the possible predisposing factors found in ICU patients show that candiduria
      surveillance should be performed to help reducing nosocomial infections.

PMID- 16444427
TI  - Pitfalls in warfarin therapy.

PMID- 16444428
TI  - The association between fibrinogen, von Willebrand Factor, antithrombin III, and
      D-dimer levels and survival outcome by 36 months from ovarian cancer.
AB  - Thirty-five patients diagnosed to have ovarian cancer (early FIGO stage I/II n =
      11, advanced FIGO stage III/IV, n = 24) were evaluated for hemostatic parameters
      relating to survival outcome by 36 months of disease. Systemic plasminogen
      activators and inhibitors were evaluated and we found no significant association
      with survival outcome and eventually only fibrinogen, von Willebrand Factor
      (vWF), antithrombin III (ATIII), and D-dimer levels were determined for their
      association with disease outcome by 12 months, 24 months, and 36 months. Twenty
      four patients succumbed to the disease by 36 months (early n = 2, advanced n =
      22). The 11 surviving patients (advanced n = 3, including one deceased at 52
      months) is still living past 36 months and 82 months at the time of analysis.
      Elevated fibrinogen, vWF, and D-dimer together with reduced ATIII levels were
      found to be associated with poor survival outcome by 12 months of disease.
      Moreover, elevated vWF and D-dimer with reduced ATIII levels was strongly
      implicated with poor survival outcome by 36 months from ovarian cancer. The
      overall survival rate at 36 months from ovarian cancer was 31.4%. It is therefore
      suggested that fibrinogen, vWF, ATIII, and D-dimer levels be used together as
      prognostic markers for disease outcome especially in patients with advanced
      ovarian cancer within 36 months of disease. An expanded study is required to
      confirm these findings.

PMID- 16444429
TI  - The effect of anthracycline-based (epirubicin) adjuvant chemotherapy on plasma
      TAFI and PAI-1 levels in operable breast cancer.
AB  - An increased incidence of thromboembolic events has been described in women
      receiving systemic chemotherapy for breast cancer. The effect of anthracycline
      based adjuvant chemotherapy regimens on fibrinolytic system markers of
      plasminogen activator inhibitor-1 (PAI-1) and thrombin activitable fibrinolysis
      inhibitor (TAFI) was investigated in patients with operable breast cancer. Twenty
      four patients with operable breast cancer (median age, 54.5 years; range, 37-72
      years) enrolled in our study. Stage I-II and stage IIIA cases received EC
      (Epirubicin 90 mg/m(2)/d1, I.V. and cyclophosphamide 600 mg/m(2)/d1, I.V.) and
      FEC (5-fluorouracil 500 mg/m(2)/d1, I.V., epirubicin 100 mg/m(2)/d1, I.V., and
      cyclophosphamide 500 mg/m(2)/d1, I.V.) as an adjuvant chemotherapy regimen,
      respectively. Each group consisted of 12 patients. Blood samples were obtained at
      baseline and just before the third cycle of EC and fourth cycle of FEC
      chemotherapy regimens. Plasma TAFI antigen and PAI-1 levels did not disclose any
      statistical difference between basal and postchemotherapy levels within each
      group and between two groups. Although postchemotherapy D-dimer levels were
      statistically higher in the FEC group than in the EC group, results in both
      groups were within normal ranges. More studies concerning the role of
      fibrinolytic system in breast cancer patients receiving chemotherapy, probably
      including cases with advanced stage and with different chemotherapy regimens and
      dose intensities, are needed.

PMID- 16444430
TI  - Hypercoagulopathy in stroke patients with nonvalvular atrial fibrillation:
      hematologic and cardiologic investigations.
AB  - The coagulation system is activated and coagulation activation markers are
      elevated in acute ischemic stroke with nonvalvular atrial fibrillation (NVAF).
      The etiology, severity, and prognosis of the ischemic stroke might be estimated
      with the level of the activation of the coagulation system. In this study,
      prothrombin F1+2 (F1+2), D-dimer, and fibrinogen levels were measured in patients
      with acute ischemic stroke with and without NVAF, and stroke severity was
      compared with these hemostatic parameters. Of 55 patients, 29 had sinus rhythm
      (group I), 26 had NVAF (group II); 20 healthy subjects (group III) were included
      in the study. Subtypes of cerebral infarction were classified. The patients
      underwent stroke severity, electrocardiography, echocardiography, cranial
      computed tomography, cervical duplex ultrasonography, and hemostatic parameter
      studies. In group II, F1+2 level (2.83+/-0.89) was significantly higher than in
      group I (2.33+/-0.80) and III (1.94+/-0.64) (p values: group I-II, 0.036; groups
      II-III, 0.001; groups I-III, 0.104). In group III, fibrinogen level (251.64+/
      60.96) was significantly lower than that in groups I (347.97+/-111.49) and II
      (364.04+/-86.20) (p=0.001). D-dimer was not significantly different between
      groups. In group I, lacunar syndrome (LACS), and in group II, partial and total
      anterior circulation syndrome (PACS+TACS) were more common (p=0.013, p=0.001,
      respectively). In group II, Scandinavian Stroke Scale scores were lower than
      those in group I (group I=45.2+/-14, group II=35.4+/-18.9, p=0.02). In
      conclusion, activation of coagulation, demonstrated by increment F1+2, is more
      abundant in the stroke patients with NVAF than in the stroke patients with sinus
      rhythm. Our results also showed that activation of the hemostatic system might be
      related to stroke subtype and stroke severity. It is suggested that the oral
      anticoagulation treatment as prophylaxis is important in the prevention of stroke
      in patients with NVAF.

PMID- 16444431
TI  - In vitro simulation of therapeutic thrombolysis with microtiter plate clot-lysis
      assay.
AB  - Only limited comparable data are available on the clot lysis power of the
      clinically used plasminogen activators (PA). Here the PA were used at different
      clinically relevant concentrations, and the lysis of the microclots was
      determined. A microclot lysis assay was used to study thrombolysis by urokinase,
      tissue-PA (t-PA), streptokinase, plasminogen-streptokinase activator complex
      (PSAC), reteplase, or tenecteplase. The clot turbidity served as a tool to
      determine clot mass: 100 microL fresh microclots were incubated with 25 microL PA
      in 6% bovine serum albumin (BSA)-phosphate-buffered saline (PBS) and 100 microL
      BSA-PBS or pooled normal human plasma; that is, the PA were in the liquid
      supernatant of a plasma clot and were not entrapped in the clot, an assay system
      comparable to normal physiology. The turbidity was determined after 0 to 5 hours
      (37 degrees C) by a microtiter plate reader. The lysable clot turbidity (clot
      mass) was expressed in percent of 100% lysable clot control. The clot lysis
      activity is 100% minus the clot mass in percent. The effective doses at 50%
      (ED(50)) of lysis of fresh clots after 4 hours (37 degrees C) with 6% BSA or
      pooled normal human plasma in the clot-supernatant were urokinase 128 or 180
      IU/mL; t-PA 0.3 or 0.2 microg/mL; streptokinase 215 or 1371 IU/mL; PSAC 60 or 91
      U/mL; reteplase 664 or 996 U/mL; tenecteplase 0.2 or 0.2 microg/mL. The presence
      of a plasma thrombus with plasma supernatant increases the activity of t-PA
      approximately 20-fold and that of tenecteplase approximately 400-fold after 4
      hours (37 degrees C), when compared to urokinase; in contrast, the lytic activity
      induced by reteplase decreases; i.e., the plasmin generated by reteplase is
      hampered on its lytic action against a thrombus. When comparing the clot
      lysability of microclots of 29 different donors, the only correlation (r > 0.6)
      was that between u-PA and t-PA. The lysability of individual clots by PA can be
      measured with the present routine-suited technique. It is suggested that
      different thrombolytic agents or concentrations thereof would have a different
      clinical outcome in different individuals.

PMID- 16444432
TI  - Third trimester maternal plasma total fibronectin levels in pregnancy-induced
      hypertension: results of a tertiary center.
AB  - The aim of this study was to evaluate maternal plasma total fibronectin values in
      pregnancy-associated hypertension in women in the third trimester of pregnancy. A
      total of 125 pregnant women at the 24th week of gestation participated in this
      study. Nonpregnant normotensive women were included as control group (n = 30).
      Plasma samples for fibronectin were obtained at the 24th, 28th, and 32nd weeks of
      gestation from all pregnant patients. From this cohort, 10 patients met the
      criteria for the diagnosis of gestational hypertension and 15 women met the
      stringent requirements of preeclampsia, whereas 100 patients were normotensive
      later in gestation. Plasma total fibronectin levels were determined by radial
      immunodiffusion technique. Data were analyzed using the SPSS program. The mean
      plasma fibronectin levels of the pregnant women in whom gestational hypertension
      and preeclampsia developed were significantly higher at the 24th, 28th, and 32nd
      weeks in comparison to normotensive pregnant women (p < 0.001). However,
      throughout the period from the 24th to 32nd weeks of pregnancy, plasma total
      fibronectin levels did not exhibit a significant change in normotensive pregnant
      patients or in patients with preeclampsia and gestational hypertension. There was
      also no correlation between plasma fibronectin levels and gestational age, mean
      arterial pressure, birth weight, and 5-minute Apgar scores in all groups (p <
      0.05). The elevated maternal plasma fibronectin level over 40 mg/dL is capable of
      predicting preeclampsia with a sensitivity of 73% and a specificity of 92%. These
      results suggest that serial plasma fibronectin measurements before 24 weeks' of
      gestation may be helpful in the early detection of preeclampsia in normotensive
      gravid women who are destined to become clinically preeclamptic.

PMID- 16444433
TI  - Antiphospholipid-mediated thrombosis: interplay between anticardiolipin
      antibodies and vascular cells.
AB  - The antiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy
      morbidity in the presence of antiphospholipid autoantibodies (aPL). aPL are a
      heterogeneous family of autoantibodies with diverse cross-reactivities whose
      origin and role have not been fully elucidated. Many of the autoantibodies
      associated with APS are directed against phospholipid-binding plasma proteins,
      such as beta2-GPI and prothrombin, or phospholipid-protein complexes. The
      mechanisms by which aPL cause thrombosis are not completely understood. There is
      no unique mechanism able to explain all symptoms associated with the presence of
      aPL. Different theories have been proposed, including the effect of aPL on
      endothelial cells, monocytes, and platelets. aPL are able to recognize, injure,
      or activate cultured vascular endothelial cells. Cultured endothelial cells
      incubated with aPL express increased levels of cell adhesion molecules and tissue
      factor (TF), an effect mediated by beta2-GPI, and may promote inflammation and
      thrombosis. Overexpression of TF has been also shown in monocytes in vitro and ex
      vivo. TF is the major initiator of coagulation in vivo; thus, its dysregulation
      may be one of the most important contributors to thrombosis. Effects of aPL upon
      platelets are not completely elucidated. aPL bind anionic phospholipid but they
      are normally in the inner side of cell membranes. When platelets are activated by
      different agonists, anionic phospholipids are exposed. There is some evidence
      showing that activated platelets are present in aPL-positive patients. Increased
      levels of beta-thrombomodulin, and microvesicle formation seem to support this
      hypothesis. Activated platelets may contribute to thrombosis by persistent
      exposure of a procoagulant surface.

PMID- 16444435
TI  - The effects of rosiglitazone treatment on the fibrinolytic system in patients
      with type 2 diabetes mellitus.
AB  - Patients with type 2 diabetes mellitus (DM) are at risk for the development of
      cardiovascular diseases, which can in part be explained by disturbances in the
      hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on
      the fibrinolytic system and insulin sensitivity in patients with type 2 DM were
      assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were
      enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue
      plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1)
      levels were measured. Insulin resistance was calculated by hoemostasis model
      assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day,
      for 12 weeks) in addition coexistent medication, and baseline tests were
      repeated. There was no difference between mean t-PA levels of the two groups. PAI
      1 levels were higher in diabetic patients than control subjects (p < 0.01).
      Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p <
      0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference
      in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was
      no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in
      diabetics. Insulin sensitivity significantly improved after the addition of
      rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low
      dose treatment with rosiglitazone in type 2 diabetic patients has no effects on
      the fibrinolytic system, although it improves insulin sensitivity.

PMID- 16444434
TI  - Effect of various genetic polymorphisms on the incidence and outcome of severe
      sepsis.
AB  - Several genetic polymorphisms have been identified in patients with sepsis and
      severe sepsis, such as the tumor necrosis factor-alpha (TNF-alpha) and TNF-beta
      genes, the interleukin-1 (IL-1) family, the IL-6, the IL-10, the CD-14, the Toll
      like receptors, plasminogen activator inhibitor type 1, and the factor V 1691G-A
      mutations. In this study, the relationship between the TNF-alpha 308G/A, the IL-6
      174 G/C, the PAI-1, the FVL, the EPCR, and the Cathepsin G (Ars 125 Ser)
      polymorphisms and the development and outcome of sepsis in pediatric patients was
      studied. TNF-alpha 308 G/A, PAI-1 4G/4G, and EPCR mutations influence the risk of
      severe sepsis in children. IL-6 174 G/C, FVL, and Cathepsin G (Ars 125 Ser) did
      not influence the incidence and mortality of severe sepsis.

PMID- 16444436
TI  - Evaluation of a rapid automated assay for analysis of von Willebrand ristocetin
      cofactor activity.
AB  - A commercially available turbidometric assay has been evaluated for the
      measurement of von Willebrand factor ristocetin cofactor activity (VWF:RCo). The
      assay is simple, rapid, and can be cost-effectively performed on automated
      coagulation analyzers. This study's aim is to illustrate the performance of the
      automated VWF:RCo assay and its capacity to identify patients with von Willebrand
      disease (VWD). By direct comparison with a conventional VWF:RCo assay, performed
      on an aggregometer, the concordance between the two assays was 96%. With minor
      modifications, the automated assay showed a detection level of 0.03 kIU/L with
      linearity to 2.00 kIU/L. The imprecision of the automated assay was reduced
      compared to the conventional assay procedure with CV of 6.8% at the 1.00 kIU/L
      level and 8.6% at the 0.30 kIU/L level. The automated VWF:RCo assay was also
      suitable as a screening test to detect VWD in patients investigated for the cause
      of an increased bleeding tendency. In this situation the automated VWF:RCo assay
      was tested simultaneously with an automated immunoassay for von Willebrand
      antigen. Receiver operating curves for the diagnosis of VWD showed a greater area
      under the curve for the automated VWF:RCo assay compared to the immunoassay, 0.98
      vs. 0.94, although the difference did not reach significance. In conclusion, the
      modified automated VWF:RCo assay shows better precision, lower detection limit,
      is faster to perform with a lower cost per test compared to the conventional
      aggregometer based VWF:RCo activity method and is an alternative to an antigen
      immunoassay as a screening test for VWD.

PMID- 16444437
TI  - The increase of blood anticardiolipin antibody depends on the underlying etiology
      in cerebral ischemia.
AB  - Although anticardiolipin antibody (aCL) has been suggested to be a potent risk
      factor for thrombosis and atherosclerosis in multiple arterial beds, conflicting
      results exist between aCL and cerebral ischemia in the general stroke population.
      To elucidate if this discrepancy relates to the heterogeneity of underlying
      etiologies, the blood beta(2)-glycoprotein I dependent-aCL in 432 Taiwanese
      adults was examined. The associated cerebral ischemia in these patients was
      classified into five subtypes according to the cause of cerebral ischemia. The
      results were compared with those in 100 healthy controls. A definite increase of
      aCL-IgG isotype was found in 41 patients (9.35%) and four controls (4.0%). The
      relative risk was 2.52. The frequency of increased aCL-IgG was 12.2%, 12.8%,
      8.8%, 3.9%, and 3.5% in patients with large-artery atherosclerotic disease,
      stroke of unknown etiology, small-artery occlusive disease, cardioembolism, and
      stroke of other known etiology, respectively. Only patients with large-artery
      atherosclerotic disease (p<0.025) and stroke of unknown etiology (p<0.05) had
      higher frequencies of increased aCL than those in control subjects. The
      frequencies of abnormal results of activated partial thromboplastin time,
      antinuclear factor, Coombs' test, and venereal disease research laboratory were
      2.84%, 1.22%, 1.02%, and 1.34% in these 41 patients, respectively. Accordingly,
      aCL-IgG selectively increases in patients with large-artery atherosclerosis and
      stroke of unknown etiology, reflecting selective activation of humoral immunity
      for aCL in the pathogenesis of cerebral ischemia.

PMID- 16444438
TI  - Difficulties in the mutation analysis of plasminogen gene: a study in two
      patients with ligneous conjunctivitis.
AB  - The absence or very low levels of plasminogen cause a rare disabling disease
      called ligneous conjunctivitis, characterized by the growth of fibrin-rich
      pseudomembranes in the conjunctiva and on other mucosal surfaces. Several
      mutations have been detected in the plasminogen gene of patients affected with
      ligneous conjunctivitis. The human plasminogen gene, located on chromosome 6, has
      a marked homology with the genes belonging to the plasminogen-apo(a) family, and
      with a number of pseudogenes and plasminogen-like genes located on chromosome 2.
      This work describes a series of nucleotide variations related to genes other than
      the plasminogen one, found during the genetic characterization of plasminogen
      defect in two unrelated patients with ligneous conjunctivitis. The results of
      automated sequences of each exon and intron-exon boundaries were compared with
      those of the human plasminogen gene from the NCBI gene bank. In particular, a co
      amplified gene on chromosome 2 mimicking a 14 bp deletion in exon 5 of the
      plasminogen gene was identified by sequencing two different bands obtained from a
      long run of the PCR exon 5 product in NuSieve agarose gel, and by PstI
      restriction enzyme analysis of the same amplicons. Moreover, 21 single nucleotide
      exchanges due to plasminogen-like genes co-amplification were observed, namely
      one in exon 1, two in exon 4, three in exons 3, 5 and 16, four in exon 13, and
      five in exon 17. In conclusion, these data confirm the difficulty of plasminogen
      genetic analysis and may help researchers to better identify the true plasminogen
      gene mutations causing molecular defects.

PMID- 16444439
TI  - Extreme thrombocytosis: what are the etiologies?
AB  - Increase platelet count or thrombocytosis, defined as a platelet count greater
      than or equal to 350 x 10(9)/L, is a common hematologic aberration seen in
      complete blood cell count. Several etiologies are documented for thrombocytosis.
      Extreme thrombocytosis, defined as a platelet count greater than or equal to
      1,000 x 10(9)/L, is rarely seen in general practice. There are limited data on
      the etiology of this abnormality. Here, a retrospective investigation for the
      etiology of severe thrombocytosis was performed. Of the 3 included reports, 535
      cases with extreme thrombocytosis were investigated for their etiologies. The 2
      defined etiologies are secondary thrombocytosis (66.6%) and clonal
      thrombocytosis. Of those cases with clonal thrombocytosis, 93.8% had
      myeloproliferative disorders, and 6.2% had essential thrombocytosis. Concerning
      bleeding and vaso-occlusive complications, all cases had these complications. In
      this study, 7.9% of the cases with secondary thrombocytosis experienced bleeding
      and vaso-occlusive complications, while 17.1% of the cases with clonal
      thrombocytosis did.

PMID- 16444440
TI  - Spontaneous renal subcapsular hematoma in an anticoagulated patient.
AB  - This is a case report of spontaneous subcapsular renal hematoma in an
      anticoagulated patient who was without excessive hypocoagulability and who was
      hemodynamically stable. Active bleeding was ruled out and a conservative
      treatment of discontinuing anticoagulant therapy was chosen. The patient was
      observed expectantly with serial abdominal computed tomography and abdominal
      ultrasound during her stay in the hospital. When diminution of the hematoma was
      detected, oral anticoagulation was resumed.

PMID- 16444441
TI  - PIA1/A2 polymorphism of the platelet glycoprotein receptor IIb/IIIIa and its
      correlation with myocardial infarction: an appraisal.
AB  - Platelet glycoprotein (GP) IIb/IIIa is a membrane receptor for fibrinogen and von
      Willebrand factor. There is considerable controversy regarding the clinical role
      of the GPIIb/IIIa PIA1/A2 as a risk factor for myocardial infarction. A summative
      analysis is performed on the recent previous reports on the GPIIb/IIIa PIA1/A2
      and its correlation to myocardial infarction. The metanalysis was performed to
      assess the correlation between the pattern of GPIIb/IIIa PIA1/A2 polymorphism and
      myocardial infarction. From 7 available case-control reports, 553 patients and
      1,059 controls are evaluated. The overall frequencies of PIA2 allele for the
      patients and controls are 0.249 and 0.221, respectively. According to this study,
      49.4% of subjects with PIA2 allele have myocardial infarction while 39.5% of
      subjects without PIA2 allele have cerebrovascular disease. From overall risk
      estimation, the subjects with PIA2 alleles have a 1.1 times higher risk to have
      myocardial infarction. According to this analysis, it is proposed that the
      pattern of GPIIb/IIIa PIA1/A2 polymorphism does not represent a useful marker of
      increased risk for myocardial infarction. In addition, the lack of association
      between the pattern of GPIIb/IIIa PIA1/A2 polymorphism and ethnicity of the
      patients was demonstrated in this study.

PMID- 16444442
TI  - Re-treatment of chronic idiopathic thrombocytopenic purpura with rituximab:
      literature review.
AB  - The aim of this literature review was to identify from published reports, the
      characteristics and response to rituximab of nine patients with chronic
      idiopathic thrombocytopenic purpura who had been re-treated after responding to
      an initial course of therapy. The female/male ratio of re-treated patients was
      eight, suggesting selection or their suitability for treatment because the
      female/male ratio of 95 initially treated patients in all published reports
      between December 1998 and June 2003 was 2. Almost three times as many females
      responded to the first course of rituximab. All second responses, where recorded,
      were complete despite two previous partial responses and one minor response. The
      duration of the second response was at least as durable and more so than the
      first. Of the nine re-treated patients, the two failures had not undergone
      splenectomy, yet had achieved a complete response to the first course. All four
      patients who had previously responded to intravenous immunoglobulin responded to
      both the initial and subsequent course of rituximab. The influence of prior
      splenectomy, response to intravenous immunoglobulin, and distinctive patterns of
      time course until platelet response suggest that there might be different
      mechanisms of response to rituximab.

PMID- 16444443
TI  - Warfarin-induced skin necrosis: a case report.
AB  - Warfarin-induced skin necrosis is an unusual complication of anticoagulation
      therapy associated with high morbidity. A patient is presented who had protein C
      deficiency and in whom this complication developed twice within a short time as a
      result of delayed diagnosis. Early recognition of this syndrome has important
      implications in the treatment of such patients and may reduce the severity of
      complications.

PMID- 16444444
TI  - Myocardial infarction and deep venous thrombosis in a young patient with Behcet
      disease.
AB  - Behcet disease (BD) is a chronic relapsing systemic vasculitic disorder affecting
      the arteries, veins, and vessels of any size. Vascular lesions in BD usually
      represent an occlusive nature suggesting a hypercoagulable/ prothrombotic state.
      Coronary arteries are rarely involved in BD. In this report, a 27-year-old male
      patient in whom myocardial infarction developed secondary to coronary arterial
      thrombosis together with deep venous thrombosis was presented. This is a review
      of the pathologic hemostasis and the prothrombotic state of BD.

PMID- 16444445
TI  - Middle cerebral arterial thrombosis in a patient with hypofibrinogenemia, 5 days
      after rFVIIa and FFP infusion.
AB  - A 13-year-old female patient is presented who had hypofibrinogenemia diagnosed as
      von Willebrand disease at 5 years of age at another hospital. She was admitted to
      the department of pediatric hematology with a severe headache, vomiting, and
      progressive right flaccid hemiplegia and lethargy. Contrast-enhanced computed
      tomography scan showed subdural hematoma in posterior parietal region of the
      brain and impending cerebellar herniation. She was given fresh-frozen plasma
      (FFP) and then activated factor VII (rFVIIa), 80 microg/kg was infused for
      replacement of von Willebrand factor. The subdural hematoma was emergently
      drained. The results of coagulation tests before infusion of FFP and rFVIIa
      revealed hypofibrinogenemia, and FFP was given every 48 hours. The patient
      recovered dramatically in a few days. Five days after rFVIIa infusion, a magnetic
      resonance angiography-proven right middle cerebral arterial thrombosis developed.
      It is an interesting point of discussion whether the middle cerebral arterial
      thrombosis was provoked as a consequence of rFVIIa and FFP infusion.

PMID- 16444446
TI  - Recombinant activated factor VII combined with desmopressin in preventing
      bleeding from dental extraction in a patient with Glanzmann's thrombasthenia.
AB  - The case of a 41-year-old woman with Glanzmann's thrombasthenia who underwent
      double dental extraction is presented. In the past, treatments with desmopressin
      (DDAVP) and tranexamic acid had often unsuccessful efficacy to stop or decrease
      bleeding. After ineffective DDAVP administration, the removal was performed
      successfully with recombinant activated factor VII (rFVIIa) infusion. rFVIIa
      infusion after DDAVP administration could be useful in patients with Glanzmann's
      thrombasthenia in which DDAVP and tranexamic acid weren't always effective.

PMID- 16444447
TI  - The glycoprotein IIIa PL(A1/A2) polymorphism--a defect responsible for the sticky
      platelet syndrome?

PMID- 16444448
TI  - Sustained response to anti-CD20 monoclonal antibody in severe acute primary
      immune thrombocytopenic purpura: report of one adult case.

PMID- 16444449
TI  - G-CSF enhances cellular fibrinolysis.

PMID- 16444450
TI  - Time course of rapid C-reactive protein reduction by pravastatin in patients with
      stable angina.
AB  - The evidence has indicated that rapid reduction of inflammatory marker, such as C
      reactive protein (CRP) could be achieved by administration of a statin. However,
      limited information is available in evaluating the short-term time course of CRP
      reduction in patients with coronary artery disease by use of a statin. Forty-two
      patients with stable angina were randomly assigned to 20 mg/d or 40 mg/d group of
      pravastatin. Blood samples were drawn at days 0, 1, and 14 for measuring lipid
      profile, CRP levels, and hepatic enzymes in all patients. The results showed that
      both doses of pravastatin induced significant reductions in median CRP levels and
      in mean CRP levels, respectively, at day 1 (20% in the 20 mg/d group and 17.6% in
      the 40 mg/d group; 15% in the 20 mg/d group and 10% in the 40 mg/d group) as well
      as at day 14 (28.6% in the 20 mg/d group and 33.3% in the 40 mg/d group; 25% in
      the 20 mg/d group and 22.8% in the 40 mg/d group) compared with baseline data
      without a dose-dependent manner. In addition, no changes were found at day 1
      regarding lipid profile; however, both doses of pravastatin induced significant
      reductions in total cholesterol (TC, 22% and 30%), and low-density lipoprotein
      (LDL) cholesterol (30% and 40%) compared with baseline at 14 days. The higher
      dose of pravastatin resulted in significantly greater reductions in TC and LDL
      cholesterol compared with the 20 mg/d dose (p = 0.05, p = 0.01, respectively). A
      less significant reduction was observed in triglycerides level (16% and 24%)
      compared with TC and LDL cholesterol. There was no significant difference in mean
      high-density lipoprotein (HDL) cholesterol levels compared with baseline in both
      groups. These data suggested that a common daily dose of pravastatin resulted in
      rapid reduction of CRP within 24 hours and of lipid profile within 2 weeks, and
      the benefit to the vascular endothelium might occur quickly by reduction of CRP
      levels, which may be clinically important for patients in a high-risk subgroup,
      such as acute coronary artery disease.

PMID- 16444451
TI  - Homocysteine level and coronary artery disease.
AB  - Atherosclerosis, and its most common manifestation, coronary artery disease
      (CAD), are rather common causes of morbidity and mortality worldwide. Recognition
      of its various risk factors is important to planning effective preventive
      measures. After the homocysteine theory was presented in 1969, attention has been
      directed toward the serum homocysteine level as a coronary artery disease risk
      factor. The authors aimed to assess the relationship between hyperhomocysteinemia
      and CAD in an Iranian population. In a case control study, 197 individuals (male:
      123 [62.4%]) who were scheduled for coronary angiography were selected. Venous
      samples were taken from the patients in fasting state before angiography. Data
      about age, sex, risk factors (eg, hypertension, diabetes, smoking,
      hyperlipidemia, obesity) were obtained from prepared questionnaires. Homocysteine
      levels in patients were measured by ELISA method. A homocysteine level above 15
      mumol/liter was considered high. Angiography reports and homocysteine levels were
      analyzed by independent sample t test, one-way ANOVA, multiple linear regression,
      and stratified analysis. In comparison with the patients with normal angiography
      reports (32.5%), patients with abnormal angiography reports (67.5%) had increased
      levels of homocysteine (p = 0.001). About 28.1% of patients with normal
      angiography reports had hyperhomocysteinemia. After further evaluation, linear
      correlations were detected between the numbers of involved vessels and
      homocysteine level (p = 0.000). Multiple linear regression analysis of data
      detected that in individuals without any risk factors, the relationship was
      stronger and more meaningful (p = 0.000). These data show that
      hyperhomocysteinemia is related to CAD as an independent risk factor. In
      individuals without any risk factors a linear correlation between homocysteine
      level and numbers of coronary artery involvement was present. If this equation is
      confirmed prospectively in other studies, the level of plasma homocysteine may he
      used as a noninvasive way of predicting the number of diseased coronary arteries.

PMID- 16444452
TI  - Increased urinary albumin excretion rates can be a marker of coexisting coronary
      artery disease in patients with peripheral arterial disease.
AB  - Coexisting coronary artery disease (CAD) is an important cause of morbidity and
      mortality in patients with peripheral arterial disease (PAD). Clinical evaluation
      and noninvasive tests have some important limitations for the detection of CAD in
      patients with PAD. The purpose of this study was to investigate whether urinary
      albumin excretion (UAE) was a sign of atherosclerotic involvement of coronary
      arteries in patients with PAD. Our study consisted of 65 consecutive patients (56
      men, 9 women, mean age; 59.7+/-7.9 years) with PAD who underwent coronary
      angiography. Urinary albumin excretion was measured in 24-hour urine samples by
      immunoprecipitation technique. PAD was defined as the presence of > or =50%
      stenotic lesions in at least 1 of the iliac, femoral, popliteal, tibialis
      anterior, tibialis posterior, or peroneal arteries. CAD was defined as > or =25%
      diameter stenosis in at least 1 coronary artery. Patients without any coronary
      lesions were accepted as having normal coronaries. Age, sex, distributions of
      coronary risk factors, and UAE rates were compared between patients with and
      without CAD. Mean UAE was 17.9+/-15.6 mg/day in the total population. Thirty
      seven percent of patients had CAD, and 63% had no coronary lesion. UAE rates were
      22.33+/-18.74 and 15.32+/-13.01 mg/day in patients with CAD and those with normal
      coronary arteries, respectively (p = 0.021). Microalbuminuria was detected in 25%
      in patients with CAD and 12% in those without coronary artery lesions (p =
      0.184). The difference was not statistically significant. The distributions of
      other risk factors and sex were not different between the 2 groups. These data
      suggest that in patients with PAD, urinary albumin excretion rates may be used to
      determine those with a high probability of CAD. Further studies are required to
      decide whether this noninvasive testing is appropriate in detecting high-risk
      patients.

PMID- 16444453
TI  - Current role of laser angioplasty of restenotic coronary stents.
AB  - Treatment of in-stent restenosis (ISR) with conventional percutaneous
      transluminal coronary angioplasty (PTCA) causes significant recurrent neointimal
      tissue growth in 30-85%. Therefore, laser ablation of intrastent neointimal
      hyperplasia before balloon dilation can be an attractive alternative. However,
      the long-term outcomes of such treatment have not been studied thoroughly enough.
      This prospective case-control study evaluated angiographic and clinical outcomes
      of PTCA alone and a combination of excimer laser coronary angioplasty (ELCA) and
      adjunct PTCA in 125 patients with ISR. ELCA was performed before balloon dilation
      in 67 patients, PTCA alone was performed in 58 patients. Basic demographic and
      clinical data were comparable in both groups. Lesions included in ELCA group were
      longer (17.1+/-9.9 vs 13.6+/-9.1 mm; p = 0.034), more complex (36.5% type C
      stenoses vs 14.3%; p = 0.006), and more frequently had reduced distal blood flow
      (TIMI <3: 18.9% vs 4.8%; p = 0.025) compared to lesions in the PTCA group.
      Immediate angiographic results of PTCA and ELCA + PTCA appeared to be comparable.
      PTCA alone was successful in 57 patients (98.3%), ELCA + PTCA, in 66 patients
      (98.5%). The rates of hospital complications were comparable (3.0% in ELCA group
      vs 8.6% in PTCA group). The 1-year follow-up showed that the rates of major
      adverse cardiac events (MACE) were comparable in the 2 groups (37.3% in ELCA
      group vs 46.6% in PTCA group). The rates of target vessel revascularization (TVR)
      within 1 year after the intervention were also similar in the 2 groups (32.8% vs
      34.5%). The data mean that ELCA in patients with complex ISR is efficient and
      safe. Despite a higher complexity of lesions in the ELCA group, no increase in
      the rate of complications was registered.

PMID- 16444454
TI  - Molecular viscosity in the normal left coronary arterial tree. Is it related to
      atherosclerosis?
AB  - The purpose of this study is to elucidate, probably for the first time, the
      distribution of molecular viscosity in the entire left coronary artery (LCA)
      tree. The governing mass, momentum, and energy flow equations were solved by
      using a previously validated 3-dimensional numerical (finite-element analysis)
      code. High-molecular-viscosity regions occur at bifurcations in regions opposite
      the flow dividers, which are anatomic sites predisposed for atherosclerotic
      development. Furthermore, high-molecular-viscosity values appear in the proximal
      regions of the LCA tree, where atherosclerosis frequently occurs. The effect of
      blood flow resistance, due to increased blood viscosity, gives rise to increased
      contact time between the atherogenic particles of the blood and the endothelium,
      probably promoting atherosclerosis. Observations suggest that, whole viscosity
      distribution within the coronary artery tree may represent a risk factor for the
      resulting atherosclerosis. This distribution can become a possible tool for the
      location of atherosclerotic lesions.

PMID- 16444455
TI  - Comparison of oscillometric and intraarterial systolic and diastolic blood
      pressures in lean, overweight, and obese patients.
AB  - To assess the effect of obesity on blood pressure measurement the authors
      obtained simultaneous oscillometric and intraarterial systolic and diastolic
      blood pressures on 188 lean, overweight, class I/II obese, and class III obese
      subjects. Oscillometric arm cuff/bladder size was selected in accordance with
      standard guidelines. Oscillometry significantly underestimated systolic and
      significantly overestimated diastolic blood pressures in each of the 4 weight
      groups studied. The differences between oscillometric and intraarterial systolic
      and diastolic pressures were not significantly different among lean, overweight,
      class I/II obese, and class III obese subjects. Thus, obesity per se does not
      influence the accuracy of blood pressure measurement. However, oscillometric
      blood pressure measurement is associated with significant error when compared to
      intraarterial blood pressure.

PMID- 16444456
TI  - Hypertension, antihypertensive therapy, and erectile dysfunction.
AB  - Erectile dysfunction represents a common problem in the male hypertensive
      population. Both erectile dysfunction and hypertension share common
      pathophysiologic pathways such as atherosclerosis and endothelial dysfunction.
      Furthermore, traditional cardiovascular risk factors affect both conditions.
      Notably, several antihypertensive medications seem to adversely affect erectile
      function whereas others may exert neutral or even favorable effects. Thus, the
      regular and meticulous clinical evaluation of hypertensive patients, as well as
      individualization of anti-hypertensive therapy, are important steps in the
      effective management of such patients. In addition, the administration of
      phosphodiesterase-5 inhibitors or apomorphine has excellent efficacy and safety
      profile in hypertensive patients irrespective of taking or not taking
      antihypertensive medications.

PMID- 16444457
TI  - A study on the safety, efficacy, and efficiency of sulodexide compared with
      acenocoumarol in secondary prophylaxis in patients with deep venous thrombosis.
AB  - This study was carried out to study the safety and efficacy of a fixed dosage of
      sulodexide compared to adjusted dosages (INR) of acenocoumarol as secondary
      prophylaxis in patients with deep vein thrombosis (DVT) in lower limbs. An
      economic evaluation based on the criteria of use in normal clinical practice was
      also performed. One hundred and fifty patients of both sexes were included, all
      over 18 years of age and diagnosed with proximal DVT of the lower limbs by color
      echo-Doppler, and with clinical evolution of less than 1 month. The patients were
      initially treated with low-molecular-weight heparin (LMWH) and urokinase in
      accordance with the established protocol. They were then randomized to continue
      treatment with acenocoumarol and INR adjustments every 30 days, or with
      sulodexide. Treatment was extended for 3 months with monthly follow-up visits and
      a final visit at 3 months posttreatment. No differences between the groups were
      detected concerning demographic or basal characteristics in clinical evolution or
      adverse reactions. In the group treated with sulodexide, no major/minor
      hemorrhagic complications were detected. On the other hand, in the acenocoumarol
      group, 1 major hemorrhage and 9 minor hemorrhages were produced (13.3%), reaching
      statistical difference in relation to the sulodexide group (p = 0.014; CI from
      95% of 4.7% to 19.4%). Regarding the economic impact, treatment costs with
      sulodexide are much less than those with acenocoumarol, the data confirmed by the
      sensitivity analyses performed. The results prove the efficacy, safety, and
      efficiency of sulodexide as a secondary prophylaxis in thromboembolic disease,
      avoiding hemorrhagic risks and the monitoring of patients, and providing
      significant savings to the health system.

PMID- 16444459
TI  - A prospective, case-control study of tobacco dependence in thromboangiitis
      obliterans (Buerger's Disease).
AB  - Thromboangiitis obliterans (TAO) is often cited as an extreme phenotype of
      vasculopathy and tobacco dependence. Although tobacco exposure is essential to
      progression of arterial ischemia in TAO, expert opinion differs regarding the
      degree of tobacco dependence in this population. The authors designed a
      prospective, case-control study to test the hypothesis that subjects with TAO
      have a greater degree of tobacco dependence than control subjects with coronary
      atherosclerosis (coronary artery disease [CAD]) do. Subjects with TAO (n = 218,
      confirmed by angiography, biopsy, or noninvasive arterial testing) or CAD (n =
      343, diagnosed by coronary angiography) were mailed a standardized questionnaire
      regarding tobacco use, to which 103 and 273 responded, respectively. The degree
      of tobacco dependence in each group was ascertained by several methods, including
      the Fagerstrom Test for Nicotine Dependence Questionnaire. The TAO group was
      younger at index date (year of first diagnosis for TAO patients, year of
      percutaneous transluminal coronary angioplasty [PTCA] for CAD patients) (TAO
      37.6+/-9.0 vs CAD 43.3+/-4.9 yr, p < 0.0001), but the groups did not differ in
      age at first tobacco exposure (TAO 16.7+/-3.1 vs CAD 17.3+/-4.2 yr, p = 0.67),
      current tobacco use at time of survey (TAO 54% vs CAD 46%, p = 0.17), or
      Fagerstrom score (TAO 4.7+/-2.3 vs CAD 5.1+/-2.3, p = 0.24). Kaplan-Meier curves
      showed no significant difference in time to topping tobacco use after first
      diagnosis (p = 0.076). TAO subjects smoked fewer cigarettes per day than CAD
      subjects (TAO 22.3+/-10.7 vs CAD 27.7+/-15.3 cigarettes/day, p = 0.003). Among
      current smokers (n = 170), TAO subjects also smoked fewer cigarettes/day (20.2+/
      8.2 vs 24.6+/-12.7, p = 0.03), and were more likely to have made a serious
      attempt to stop (97% vs 90%, p = 0.03). In contrast to case reports of extreme
      tobacco dependence in the TAO population, the degree of tobacco dependence in
      subjects with TAO is similar to that in subjects with CAD.

PMID- 16444458
TI  - Short-term lipid-lowering treatment with atorvastatin improves renal function but
      not renal blood flow indices in patients with peripheral arterial disease.
AB  - Some studies have suggested that lipid lowering with statins exerts favorable
      effects on the progression of chronic kidney disease. Therefore, the authors
      assessed the effects of short-term atorvastatin treatment on biochemical markers
      of renal function and evaluated duplex indices of renal blood flow (RBF) in
      patients with peripheral arterial disease. Hyperlipidemic claudicants (n = 18),
      aged 44-85 years, were treated for 8 weeks with 20 mg/day atorvastatin. Blood
      tests at baseline and after 8 weeks included serum fasting lipids, creatinine,
      urate, and cystatin C (a sensitive indicator of renal function) levels. RBF was
      also assessed (n = 9) by measuring pulsatile and resistance duplex indices. As
      expected, there was a significant improvement in total cholesterol, low-density
      lipoprotein cholesterol, and triglycerides. There was also a significant (p <
      0.0001) fall in serum creatinine from 89 (58-125) to 79 micromol/L (54-119) and
      an increase in calculated creatinine clearance (CrCl) from 72 (40-129) to 80
      mL/minute (47-138; p < 0.0001). Serum cystatin C values decreased significantly
      (p = 0.0002) from 1.04 (0.57-1.56) to 0.90 mg/L (0.47-1.47). There were no
      detectable changes in the RBF duplex indices. Treatment of stable claudicants
      with atorvastatin for 8 weeks was associated with improved renal function (as
      assessed by serum creatinine, cystatin C, and calculated CrCl) without changes in
      RBF. Further studies are required to identify the mechanisms involved in this
      phenomenon.

PMID- 16444460
TI  - Recurrent thrombosis in patients with deep vein thrombosis and/or venous
      thromboembolism associated with anticardiolipin antibodies.
AB  - Anticardiolipin antibodies represent one of the main hypercoagulation states
      associated with venous thromboembolism. The aim of this work was to evaluate
      symptomatic recurrent thrombosis in patients with anticardiolipin antibodies and
      deep vein thrombosis of the lower limbs with or without thromboembolism. Sixty
      patients who suffered from deep vein thrombosis were observed for a 5-year
      period, whether they had anticardiolipin antibodies or not. The group was made up
      of 34 females and 26 males with ages ranging from 13 to 73 years. All were
      diagnosed with deep vein thrombosis by means of phlebography and were tested for
      anticardiolipin antibodies by use of the ELISA method. The symptomatic signs of
      recurrent thrombosis were evaluated during this period. In total, 56.6% of the
      group were considered above normal for anticardiolipin antibodies, 25% positive,
      another 31.6% borderline, and 43.4% negative. Patients were tested positive when
      the anticardiolipin antibody count was >15 units/mL, borderline between 10 and 15
      units/mL, and normal when <10 units/mL. The method of relative risk was used for
      statistical analysis of the results. Four positive patients, 1 borderline, and 1
      normal patient had recurrent events of thrombosis. In the statistical analysis
      the relative risk for recurrent thrombosis in the positive patients was 6.0; CI
      95%; 1.2 to 29.5. In conclusion patients with deep vein thrombosis who are
      positive for anticardiolipin antibodies present a higher risk of recurrent
      thrombosis.

PMID- 16444461
TI  - Visceral fat obesity contributes to the tortuosity of the thoracic aorta on chest
      radiograph in poststroke Japanese patients.
AB  - Tortuosity of the thoracic aorta on chest radiographs is characteristic of
      atherosclerotic disease. Aging and hypertension are associated with the
      tortuosity, but little is known about the influence of other atherosclerotic risk
      factors on this abnormality. The purpose of this study was to examine which
      atherosclerotic risk factors are determinants for tortuosity of the thoracic
      aorta. Forty-five poststroke Japanese patients (31 men and 14 women, age range 41
      78 years and mean 60.5+/-8.6) were studied. The distance factor, ie, the ratio of
      meandering vessel length to the straight-line distance between its end points,
      was used to measure arterial tortuosity. The hospital records were reviewed for
      clinical and biochemical variables. Tortuosity of the thoracic aorta had a
      significant positive relationship with body mass index (BMI) (r = 0.397, p <
      0.01), waist circumference (r = 0.360, p < 0.05), and the cardiothoracic ratio
      (CTR) (r = 0.526, p < 0.001), and a significant negative relationship with ankle
      brachial pressure index (ABPI) (r = -0.360, p < 0.05). Stepwise regression
      analysis showed that waist circumference and CTR were independently correlated
      with increased tortuosity, whereas ABPI was negatively correlated with it. These
      results suggest that visceral fat obesity is a novel contributor to tortuosity of
      the thoracic aorta, which may be as shortening of the distance between aortic
      tethering points due to elevation of the diaphragm by excessive intraabdominal
      fat and as a consequence of aortic elongation due to arteriosclerosis caused by
      obesity-related metabolic disorders.

PMID- 16444462
TI  - Does p-wave dispersion predict the atrial fibrillation occurrence after direct
      current shock therapy?
AB  - Supraventricular tachycardia attacks, including atrial fibrillation (AF), occur
      after both external and internal cardioversions. These attacks of atrial
      fibrillation after direct-current (DC) shock may be related to hemodynamic
      impairment, thromboembolic events, or enhanced electrical instability of the
      ventricular and atrial myocardium, especially in predisposed patients. In this
      study, the authors aimed to show the importance of P-wave dispersion (PWD), which
      lead the atrium to fibrillate, in predicting post-DC shock AF after external
      cardioversion. Thus physicians may be able to choose the patients with high risk
      for AF occurrence and apply some other therapeutic modalities to those patients.
      The authors identified 18 patients in whom an AF attack was induced by urgent or
      elective cardioversion for a ventricular tachycardia attack and compared these
      patients with a control group composed of 40 patients without AF in regard to
      some clinical, echocardiographic, and electrocardiographic parameters. Left
      atrial diameters were greater (4.3+/-0.3 vs 3.5+/-0.5 cm, p = 0.001), left
      ventricular ejection fractions (LVEF) were lower (45.2+/-8.2 vs 54.9+/-7.5, p =
      0.001), the energy needed for successful cardioversion was higher (166.6+/-59.4
      vs 80.8+/-51.6 J, p = 0.001), and P max (135.2+/-7.4 vs 118.7+/-10.5 ms, p =
      0.001) and PWD (53.8+/-12.2 vs 23.8+/-9.5 ms, p = 0.001) values were higher in
      patients with AF when compared to those without AF. Thus, the patients with
      higher PWD values had a greater risk for development of AF after a DC shock.

PMID- 16444463
TI  - The prostacyclin analog, treprostinil sodium, provides symptom relief in severe
      Buerger's disease--a case report and review of literature.
AB  - Buerger's disease (thromboangiitis obliterans or TAO) is a clinical syndrome
      characterized by the development of segmental thrombotic occlusions of the medium
      and small arteries. The primary treatment for Buerger's disease is cessation of
      cigarette smoking. In patients whose disease progresses despite smoking
      cessation, therapeutic options are limited. Revascularization is rarely indicated
      and usually not successful because of the diffuse and distal distribution of the
      disease. Prostacyclin, or PGI2, and its analogs have been proposed as
      pharmacotherapy for Buerger's disease and studied in Europe. The authors review
      the prostacyclin literature in the treatment of Buerger's disease and present a
      case report of a patient with progressive Buerger's disease and the use of
      treprostinil sodium (Remodulin). This case report experience suggests hat
      subcutaneous treprostinil therapy could be clinically useful in Buerger's disease
      that does not improve with smoking cessation, particularly in the presence of
      critical limb ischemia where other therapeutic options have failed.

PMID- 16444464
TI  - Recurrent tuberculous pseudoaneurysm of the descending thoracic aorta--a case
      report.
AB  - Tuberculous pseudoaneurysm of the aorta is a rare disease that is uniformly fatal
      if not treated properly. The authors present a case of a recurrent tuberculous
      false aneurysm of the descending thoracic aorta that was treated surgically with
      excision and primary repair of the lesion. To their knowledge, this is the first
      reported case of recurrent disease after a successful surgical treatment.

PMID- 16444465
TI  - Occupation-related vascular disorders of the upper extremity--two case reports.
AB  - Hypothenar hammer (HH) syndrome and vibration-induced white finger (VWF) syndrome
      are the main occupation-related vascular diseases of the upper extremity. The
      clinical presentation is similar to that of Raynaud's phenomenon. The
      characteristic history will lead to the appropriate diagnosis being confirmed by
      angiographic features in HH and by functional tests in VWF. While in HH the
      underlying cause, which is mostly thought to be an aneurysm of the ulnar artery,
      might be cured surgically, in VWF only medical treatment offers relief from the
      symptoms. The knowledge of these entities is necessary to suspect such disorders
      so that further exposure to risk factors like repetitive hypothenar trauma or
      work with vibrating hand-held tools can be avoided, which is of great importance
      for the overall prognosis of these patients.

PMID- 16444466
TI  - Bilateral external iliac artery catheter-induced vasospasm during angiography--a
      case report.
AB  - The occurrence of catheter-induced vasospasm of small-caliber arteries during
      cardiac angiography is well documented. In contrast, little documentation of
      catheter-induced vasospasm in large-caliber arteries exists. This case presents
      reproducible catheter-induced vasospasm with bilateral asymptomatic occlusion of
      the femoral and iliac arteries.

PMID- 16444467
TI  - Severe left ventricular dysfunction in left atrial myxoma--report of 2 cases.
AB  - We report 2 patients with left atrial (LA) myxoma with associated severe left
      ventricular (LV) dysfunction. Both presented with progressive effort intolerance
      without a history suggestive of acute coronary event. LA myxoma was diagnosed by
      transthoracic echocardiography, which also detected severe systolic dysfunction
      and LV dilatation. Regional wall motion abnormality and thinning were absent.
      Coronary angiograms also showed no occlusive disease, but distal ectasia was seen
      in 1 patient. Metabolic and endocrine causes of reversible LV dysfunction were
      excluded. Cardiac function improved following surgery for myxoma in 1 patient. LV
      dysfunction, thus far, has not been directly attributed to myxoma. Coronary
      embolization leading to myocardial infarction and coexisting coronary
      atherosclerosis are the recognized methods by which LV dysfunction manifests in
      myxoma. Our report suggests the possibility of reversible severe global LV
      dysfunction due to cardiodepressant effect of myxoma through as yet unclear
      mechanisms.

PMID- 16444468
TI  - Recurrent aortic angiosarcoma--a case report and review of the literature.
AB  - Primary aortic tumors are rare; only 86 cases of primary aortic angiosarcoma have
      been reported since its first description in 1873. The diagnosis of aortic
      angiosarcoma is usually confirmed by postoperative pathologic examination or
      postmortem study. The authors present a case of primary aortic angiosarcoma with
      postresection recurrence.

PMID- 16444495
TI  - Transobturator tape, bladder perforation, and paravaginal defect: a case report.
AB  - Transobturator midurethral slings (TOT) have been shown to have less risk of
      vascular and visceral injury than tension-free midurethral slings. Routine
      cystoscopy has therefore not been felt to be necessary. A case of bladder
      perforation unrecognized at the time of TOT placement is presented. Findings at
      sling removal suggested that a clinically nonapparent paravaginal defect may have
      been instrumental in the injury. Consideration should be given to routine
      cystoscopy at the time of transobturator sling placement.

PMID- 16444469
TI  - Recurrent peripheral arterial embolism from metastatic lung choriocarcinoma--a
      case report.
AB  - A patient with choriocarcinoma, most likely of ovarian origin, with lung
      metastasis is presented. The disease manifested itself by recurrent embolism into
      the peripheral arteries. Literature on this topic is reviewed.

PMID- 16444515
TI  - A model for the human cornea: constitutive formulation and numerical analysis.
AB  - Abstract The human cornea (the external lens of the eye) has the macroscopic
      structure of a thin shell, originated by the organization of collagen lamellae
      parallel to the middle surface of the shell. The lamellae, composed of bundles of
      collagen fibrils, are responsible for the experimentally observed anisotropy of
      the cornea. Anomalies in the fibril structure may explain the changes in the
      mechanical behavior of the tissue observed in pathologies such as keratoconus. We
      employ a fiber-matrix constitutive model and propose a numerical model for the
      human cornea that is able to account for its mechanical behavior in healthy
      conditions or in the presence of keratoconus under increasing values of the
      intraocular pressure. The ability of our model to reproduce the behavior of the
      human cornea opens a promising perspective for the numerical simulation of
      refractive surgery.

PMID- 16444517
TI  - Recoverin as a cancer-retina antigen.
AB  - In photoreceptor cells the Ca(2+) -binding protein recoverin controls
      phosphorylation of the visual receptor rhodopsin by inhibiting rhodopsin kinase
      (GRK-1). It can also serve as a paraneoplastic antigen in the development of
      retinal degeneration in some patients with cancer. The aberrant expression of
      recoverin in cancer cells and the presence of autoantibodies against recoverin
      are essential for the occurrence of cancer-associated retinopathy, which finally
      results in the apoptosis of photoreceptor cells. Noteworthy in cancer patients,
      the aberrant recoverin expression and the appearance of autoantibodies against
      recoverin are more frequent than paraneoplastic syndromes. We suggest the term
      "cancer-retina antigens" for this kind of proteins like recoverin that are solely
      expressed in retina and tumor tissues and evoke antibodies and/or T cells in
      patients with cancer. The rare development of a paraneoplastic syndrome is
      possibly caused by this immune response and probably depends on further events
      allowing to overcome the blood-retina barrier and the immune privileged status of
      the retina. It is still unknown whether aberrantly expressed recoverin could have
      a specific function in cancer cells, though it is suggested that it can be
      functionally associated with G-protein-coupled receptor kinases. This paper
      reviews the present knowledge on paraneoplastic syndromes associated with the
      aberrant expression of recoverin. A possible application of recoverin as a
      potential target for immunotherapy of cancer is discussed.

PMID- 16444539
TI  - Glycerophosphate as a phosphorus source in a defined medium for Pichia pastoris
      fermentation.
AB  - Pichia pastoris has emerged as a commercially important yeast for the production
      of a vast majority of recombinant therapeutic proteins and vaccines. The organism
      can be grown to very high cell densities using a defined basal salts media (BSM).
      However, BSM contains bi-cation or tri-cation phosphate, which precipitates out
      of the medium at pH above 5.5, although the optimal fermentation pH of most
      recombinant protein fermentation varies between 5.5 and 7.0. In this article, the
      application of glycerophosphates was investigated as a substitute phosphate
      source in an effort to eliminate precipitation. The solubility of BSM containing
      sodium or potassium glycerophosphates was examined before and after autoclaving
      at various pHs. Sodium glycerophosphate was found stable at autoclave temperature
      but formed complexes with coexisting magnesium and calcium ions that were
      insoluble above pH 7.0. Medium where sodium glycerophosphate was autoclaved
      separately and then added to the growth medium did not produce any precipitate up
      to pH 10.5. The performance of P. pastoris fermentations expressing alpha
      galactosidase and ovine interferon-tau using a glycerolphosphate-based medium was
      found to be comparable to a conventional BSM. The results from this work
      demonstrate that sodium glycerophosphate can be assimilated by the P. pastoris
      strains and can be employed as a reliable phosphorus source for both cell growth
      and recombinant protein production.

PMID- 16444562
TI  - Prognostic analysis of clinicopathologic factors in 49 patients with diffuse
      malignant peritoneal mesothelioma treated with cytoreductive surgery and
      intraperitoneal hyperthermic perfusion.
AB  - BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a subset of
      peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic
      analysis in a cohort of DMPM patients treated homogeneously by cytoreductive
      surgery and intraperitoneal hyperthermic perfusion (IPHP). METHODS: Forty-nine
      DMPM patients who underwent 52 consecutive procedures were enrolled onto the
      study. Cytoreductive surgery was performed according to the peritonectomy
      technique, and the IPHP was performed with cisplatin plus doxorubicin or
      cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic
      variables (previous surgical score, age, sex, performance status, previous
      systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction,
      IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers
      [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix
      metalloproteinase 9]) with overall and progression-free survival. RESULTS: The
      mean age was 52 years (range, 22-74 years). The mean follow-up was 20.3 months
      (range, 1-89 months). Regarding the biological markers, the rates of
      immunoreactivity of epidermal growth factor receptor, p16, matrix
      metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%,
      respectively. The strongest factors influencing overall survival were
      completeness of cytoreduction and MC, whereas those for progression-free survival
      were performance status and MC. No biological markers were shown to be of
      prognostic value. CONCLUSIONS: Completeness of cytoreduction, performance status,
      and MC seem to be the best determinants of outcome. These data warrant
      confirmation by a further prospective formal trial. No biological markers
      presented a significant correlation with the outcome. The overexpression of
      epidermal growth factor receptor, matrix metalloproteinase 2, and matrix
      metalloproteinase 9 and absent or reduced expression of p16 might be related to
      the underlining tumor kinetics of DMPM and warrant further investigation with
      other methods.

PMID- 16444580
TI  - Glioma: what is the role of c-Myc, hsp90 and telomerase?
AB  - The continuous advancements in cancer research have contributed to the
      overwhelming evidence of the presence of telomerase in primary and secondary
      tumours together with hsp90 and c-Myc. This review will discuss the important
      role of telomerase together with hsp90 and c-Myc within the initiation and
      progression of gliomas. Also it will review the differential expression of these
      genes in the different grades of gliomas and the possibility of new treatments
      targeting these specific genes.

PMID- 16444581
TI  - Inhibition of adenosine kinase by phosphonate and bisphosphonate derivatives.
AB  - The enzyme adenosine kinase (AK) plays a central role in regulating the
      intracellular and interstitial concentration of the purine nucleoside adenosine
      (Ado). In view of the beneficial effects of Ado in protecting tissues from
      ischemia and other stresses, there is much interest in developing AK inhibitors,
      which can regulate Ado concentration in a site- and event-specific manner. The
      catalytic activity of AK from different sources is dependent upon the presence of
      activators such as phosphate (Pi). In this work we describe several new
      phosphorylated compounds which either activate or inhibit AK. The compounds
      acetyl phosphate, carbamoyl phosphate, dihydroxyacetone phosphate and
      imidodiphosphate were found to stimulate AK activity in a dose-dependent manner
      comparable to that seen with Pi. In contrast, a number of phosphonate and
      bisphosphonate derivatives, which included clodronate and etidronate, were found
      to inhibit the activity of purified AK in the presence of Pi. These AK inhibitors
      (viz. clodronate, etidronate, phosphonoacetic acid, 2-carboxyethylphosphonic
      acid, N-(phosphonomethyl)-glycine and N-(phosphonomethyl)iminodiacetic acid), at
      concentrations at which they inhibited AK, were also shown to inhibit the uptake
      of (3)H-adenosine and its incorporation into macromolecules in cultured mammalian
      cells, indicating that they were also inhibiting AK in intact cells. The drug
      concentrations at which these effects were observed showed limited toxicity to
      the cultured cells, indicating that these effects are not caused by cellular
      toxicity. These results indicate that the enzyme AK provides an additional
      cellular target for the clinically widely used bisphosphonates and related
      compounds, which could possibly be exploited for a new therapeutic application.
      Our structure-activity studies on different AK activators and inhibitors also
      indicate that all of the AK activating compounds have a higher partial positive
      charge (delta(+)) on the central phosphorous atom in comparison to the
      inhibitors. This information should prove helpful in the design and synthesis of
      more potent inhibitors of AK.

PMID- 16444582
TI  - Seven day oral supplementation with Cardax (disodium disuccinate astaxanthin)
      provides significant cardioprotection and reduces oxidative stress in rats.
AB  - In the current study, the improved oral bioavailability of a synthetic
      astaxanthin derivative (Cardax; disodium disuccinate astaxanthin) was utilized to
      evaluate its potential effects as a cardioprotective agent after 7-day subchronic
      oral administration as a feed supplement to Sprague-Dawley rats. Animals received
      one of two concentrations of Cardax in feed (0.1 and 0.4%; approximately 125 and
      500 mg/kg/day, respectively) or control feed without drug for 7 days prior to the
      infarct study carried out on day 8. Thirty minutes of occlusion of the left
      anterior descending (LAD) coronary artery was followed by 2 h of reperfusion
      prior to sacrifice, a regimen which resulted in a mean infarct size (IS) as a
      percentage (%) of the area at risk (AAR; IS/AAR,%) of 61 +/- 1.8%. The AAR was
      quantified by Patent blue dye injection, and IS was determined by
      triphenyltetrazolium chloride (TTC) staining. Cardax at 0.1 and 0.4% in feed for
      7 days resulted in a significant mean reduction in IS/AAR,% to 45 +/- 2.0% (26%
      salvage) and 39 +/- 1.5% (36% salvage), respectively. Myocardial levels of free
      astaxanthin achieved after 7-day supplementation at each of the two
      concentrations (400 +/- 65 nM and 1634 +/- 90 nM, respectively) demonstrated
      excellent solid-tissue target organ loading after oral supplementation. Parallel
      trends in reduction of plasma levels of multiple lipid peroxidation products with
      disodium disuccinate astaxanthin supplementation were observed, consistent with
      the documented in vitro antioxidant mechanism of action. These results extend the
      potential utility of this compound for cardioprotection to the elective human
      cardiovascular patient population, for which 7-day oral pre-treatment (as with
      statins) provides significant reductions in induced periprocedural infarct size.

PMID- 16444583
TI  - Expression and characterization of wild-type TFPI and the [P151L]TFPI mutant in
      insect cells.
AB  - Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type serine
      proteinase inhibitor that plays a central role in the extrinsic pathway of blood
      coagulation. In earlier studies we could identify the [P151L]TFPI mutant, and we
      could also demonstrate that heterozygous carriers of this mutant show a nine-fold
      increased risk for deep venous thrombosis (DVT). To express greater amounts of
      both proteins and to enable their characterization, we expressed wild-type TFPI
      as well as [P151L]TFPI in High Five insect cells with expression rates of up to
      215 ng/ml for wild-type TFPI and 214 ng/ml for [P151L]TFPI. The specific
      inhibitory activities for the recombinant proteins were determined as 11.3 and
      11.5 mU/ng, respectively. Both proteins were detected via Western blot analysis
      and ELISA. The recombinant proteins' inhibitory activities were characterized by
      a chromogenic assay and by the determination of a modified activated
      thromboplastin time (aPTT) in which both of them proved to be inhibitorily
      active. We also examined both recombinant proteins' binding properties to
      glycoproteins, glycosaminoglycans, lipoproteins and tissue factor. Our results
      show that we have developed an efficient model system for the recombinant
      expression of inhibitorily active wild-type TFPI as well as [P151L]TFPI in insect
      cells, and we were able to characterize both proteins' inhibitory properties by
      determination of their influence on the aPTT and also their binding properties.
      Although both recombinant proteins did not show a significant difference in their
      effect on the aPTT, their binding properties differed significantly between the
      wild type and mutant protein.

PMID- 16444585
TI  - Inhibitory effects of Azadirachta indica on DMBA-induced skin carcinogenesis in
      Balb/c mice.
AB  - Male Balb/c mice were divided into four groups on the basis of their respective
      treatments wherein mice of Group I served as controls. For induction of skin
      tumors, mice of Group II and IV were injected sub-cutaneously with 7,12
      dimethylbenz(a)anthracene (DMBA). Mice of Group III and IV were administered
      aqueous Azadirachta indica leaf extract (AAILE) thrice a week throughout the
      experiment. After 14 weeks of the first DMBA injection, Group II and IV mice
      developed tumors. In the tumor-bearing mice that received AAILE (Group IV), a
      significant reduction in mean tumor burden and tumor volume was observed. The
      tumors were confirmed to be papillomas and interestingly, the extent of hyper
      chromatia was observed to be much more in skin tumors of Group II mice vis a vis
      the mice receiving AAILE. An increase in the extent of lipid peroxidation was
      observed in tumorous tissue of Group IV when compared to that of Group II mice.
      Glutathione (GSH) content and the activities of GSH-based antioxidant enzymes
      viz. glutathione peroxidase (GPx) and glutathione reductase (GR) increased
      significantly in the skin tissues of all the groups of mice when compared to
      control counterparts. Catalase activity was found to decrease significantly in
      the skin of mice, which received AAILE treatment only (Group III). Activity of
      super-oxide dismutase (SOD) decreased significantly in all the tumorous tissues
      (Group II and IV mice). In light of the above observations, the role of AAILE in
      inhibition of DMBA-induced skin carcinogenesis is discussed in the present study.

PMID- 16444584
TI  - Protective effects of ginkgo biloba against acetaminophen-induced toxicity in
      mice.
AB  - BACKGROUND: The analgesic acetaminophen (AAP) causes a potentially fatal, hepatic
      centrilobular necrosis when taken in overdose. It was reported that these toxic
      effects of AAP are due to oxidative reactions that take place during its
      metabolism. OBJECTIVE: In this study, we aimed to investigate the possible
      beneficial effect of Ginkgo biloba (EGb), an antioxidant agent, against AAP
      toxicity in mice. METHODS: Balb/c mice were injected i.p. with: (1) vehicle,
      control (C) group; (2) a single dose of 50 mg/kg Ginkgo biloba extract, EGb
      group; (3) a single dose of 900 mg/kg i.p. acetaminophen, AAP group, and (4) EGb,
      in a dose of 50 mg/kg after AAP injection, AAP + EGb group. Serum ALT, AST, and
      tumor necrosis factor-alpha (TNF-alpha) levels in blood and glutathione (GSH),
      malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and collagen
      contents in liver tissues were measured. Formation of reactive oxygen species in
      hepatic tissue samples was monitored by using chemiluminescence (CL) technique
      with luminol and lusigenin probe. Tissues were also examined microscopically.
      RESULTS: ALT, AST levels, and TNF-alpha were increased significantly (p < 0.001)
      after AAP treatment, and reduced with EGb. Acetaminophen caused a significant (p
      < 0.05-0.001) decrease in GSH levels while MDA levels and MPO activity were
      increased (p < 0.001) in liver tissues. These changes were reversed by EGb
      treatment. Furthermore, luminol and lusigenin CL levels in the AAP group
      increased dramatically compared to control and reduced by EGb treatment (p <
      0.01). CONCLUSION: Our results implicate that AAP causes oxidative damage in
      hepatic tissues and Ginkgo biloba extract, by its antioxidant effects protects
      the tissues. Therefore, its therapeutic role as a "tissue injury-limiting agent"
      must be further elucidated in drug-induced oxidative damage.

PMID- 16444586
TI  - Sterol carrier protein-2 expression alters sphingolipid metabolism in transfected
      mouse L-cell fibroblasts.
AB  - The influence of sterol carrier protein-2 (SCP-2) on the cellular metabolism of
      sphingolipids was examined in control mouse L-cells and stably transfected clones
      expressing the protein SCP-2. Three approaches were used to examine for
      differences; (1) compositional analysis of endogenous sphingolipid classes, (2)
      metabolism of NBD-ceramide, and (3) live cell labelling via endocytic uptake of
      BODIPY-sphingomyelin. SCP-2 over expression significantly altered the endogenous
      levels of both neutral and acidic sphingolipid classes. Among the neutral
      sphingolipids, expression of SCP-2 induced a 1.7-fold increase in the level of
      lactosylceramide (LacCer, p < 0.05) and a similar fold decrease in the level of
      the higher-order neutral glycosylceramides (p < 0.05). Among the acidic
      sphingolipids, SCP-2 resulted in a 5.2-fold decrease in the endogenous plasma
      membrane level of ganglioside GM1 (p < 0.03). Incubation of both control and
      transfected cell lines with NBD-ceramide resulted in the rapid establishment of a
      steady-state distribution of NBD-labelled sphingomyelin (NBD-SM) and
      glucosylceramide (NBD-GlcCer). In the SCP-2 expressing clones the conversion of
      NBD-Cer to NBD-GlcCer was 30% lower during incubation periods between 5 and 30
      min (p < 0.025). Inspection of the cells by fluorescence microscopy after
      incubation with BODIPY labelled sphingomyelin (BODIPY-SM) revealed similar
      punctuated patterns with no distinguishable differences between the cell types.
      These results imply that SCP-2 plays a role in modulating enzymatic steps
      involved in metabolism of sphingolipid homeostasis.

PMID- 16444588
TI  - Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor
      activation and nitric oxide production.
AB  - Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has
      a beneficial effect on the cardiovascular system during stress conditions, but
      the defence mechanism is still unclear. The present study was designed to
      investigate the central (CB1) and the peripheral (CB2) cannabinoid receptor
      expression in neonatal cardiomyoctes and possible function in the
      cardioprotection of THC from hypoxia. Pre-treatment of cardiomyocytes that were
      grown in vitro with 0.1 - 10 microM THC for 24 h prevented hypoxia-induced
      lactate dehydrogenase (LDH) leakage and preserved the morphological distribution
      of alpha-sarcomeric actin. The antagonist for the CB2 (10 microM), but not CB1
      receptor antagonist (10 microM) abolished the protective effect of THC. In
      agreement with these results using RT-PCR, it was shown that neonatal cardiac
      cells express CB2, but not CB1 receptors. Involvement of NO in the signal
      transduction pathway activated by THC through CB2 was examined. It was found that
      THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via
      CB2 receptors. L-NAME (NOS inhibitor, 100 microM) prevented the cardioprotection
      provided by THC. Taken together, our findings suggest that THC protects cardiac
      cells against hypoxia via CB2 receptor activation by induction of NO production.
      An NO mechanism occurs also in the classical pre-conditioning process; therefore,
      THC probably pre-trains the cardiomyocytes to hypoxic conditions.

PMID- 16444587
TI  - Effect of Triphala on oxidative stress and on cell-mediated immune response
      against noise stress in rats.
AB  - Stress is one of the basic factors in the etiology of number of diseases. The
      present study was aimed to investigate the effect of Triphala (Terminalia
      chebula, Terminalia belerica and Emblica officinalis) on noise-stress induced
      alterations in the antioxidant status and on the cell-mediated immune response in
      Wistar strain male albino rats. Noise-stress employed in this study was 100 dB
      for 4 h/d/15 days and Triphala was used at a dose of 1 g/kg/b.w/48 days. Eight
      different groups of rats namely, non-immunized: control, Triphala, noise-stress,
      Triphala with noise-stress, and corresponding immunized groups were used. Sheep
      red blood cells (5 x 10(9) cells/ml) were used to immunize the animals.
      Biochemical indicators of oxidative stress namely lipid peroxidation,
      antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
      (GPx), ascorbic acid in plasma and tissues (thymus and spleen) and SOD, GPx and
      corticosterone level in plasma were estimated. Cell-mediated immune response
      namely foot pad thickness (FPT) and leukocyte migration inhibition (LMI) test
      were performed only in immunized groups. Results showed that noise-stress
      significantly increased the lipid peroxidation and corticosterone level with
      concomitant depletion of antioxidants in plasma and tissues of both non-immunized
      and immunized rats. Noise-stress significantly suppressed the cell-mediated
      immune response by decreased FPT with an enhanced LMI test. The supplementation
      with Triphala prevents the noise-stress induced changes in the antioxidant as
      well as cell-mediated immune response in rats. This study concludes that Triphala
      restores the noise-stress induced changes may be due to its antioxidant
      properties.

PMID- 16444589
TI  - Shiga toxin exposure modulates intestinal brush border membrane functional
      proteins in rabbit ileum.
AB  - The activities of lactase, sucrase and alkaline phosphatase (AP) were studied in
      intestinal brush border membranes of control and toxin-treated rabbits. Purified
      Shiga toxin (Stx) exposure to ileal mucosa inhibited activities of brush border
      enzymes by 50%. Kinetic analysis revealed that the observed decrease in BBM
      enzyme activities was due to reduced V(max) with no change in the affinity
      constants of the systems. The observed changes in enzyme activities were
      corroborated by Western Blot analysis of lactase, sucrase and AP. The mRNA levels
      encoding sucrase and lactase proteins in control and Shiga toxin-treated rabbit
      ileum did not show any change in the rabbit ileum. Histopathological analysis
      showed short, blunt villi with increased number of inflammatory cells in the
      lamina propria and extrusion of cells in to the lumen of Stx-treated rabbit
      ileum. The present findings suggest that Shiga toxin act by inhibiting protein
      synthesis of these brush border functional proteins beyond their transcriptional
      level and by the direct damage to intestinal epithelium, which could be
      implicated in the pathogenesis of diarrhea.

PMID- 16444591
TI  - Melatonin increases NMDA receptor subunits 2A and 2B concentrations in rat
      hippocampus.
AB  - We investigated that the effects of melatonin on N-methyl-D: -aspartat receptor
      (NMDAR) subunits 2A and 2B concentrations and on markers of oxidative stress in
      hippocampus of rats treated with melatonin for 4 weeks. Animals were divided into
      four groups according to their melatonin doses (control group (C), n = 7; 5 mg/kg
      group (M5), n = 7; 10 mg/kg group (M10), n = 8; 20 mg/kg group (M20), n = 8) and
      received the melatonin as intraperitoneal injection. After 4 weeks of treatment,
      electrophoretic examination was done using sodium dodecyl sulfate/polyacrilamide
      gel electrophoresis (SDS-PAGE) and Western blotting in hippocampal homogenates of
      different groups. Malondialdehyde (MDA), an end product of lipid peroxidation,
      was assayed in all groups. There were significant increases in both NMDAR 2A; 5
      mg/kg group (n = 3, p < 0.05), 10 mg/kg group (n = 3, p < 0.05), 20 mg/kg group
      (n = 3, p < 0.05) and NMDAR 2B expressions; 5 mg group (n = 3, p < 0.05), 10 mg
      group (n = 3, p < 0.05), 20 mg group (n = 3, p < 0.05), compared to the control
      group. No significant difference in MDA concentrations was found between groups.
      The present study clearly demonstrates that melatonin alters hippocampal NMDAR
      subunit concentrations in a dose-dependent manner without causing lipid
      peroxidation.

PMID- 16444590
TI  - Upregulation of the alpha1-adrenoceptor-induced phosphoinositide and inotropic
      response in hypothyroid rat heart.
AB  - In this study, we examined changes in the biochemical and inotropic events of the
      alpha(1)-adrenoceptor signaling pathway in hypothyroid rat hearts. Hypothyroidism
      was induced by treating experimental animals with 0.05% 6-n-propyl-2-thiouracil
      (PTU) in drinking water for 7 weeks. A significant decrease of beta- and an
      increase in alpha(1)-adrenoceptor density as well as an increase in the basal
      activity of the phosphoinositide (4,5) bisphosphate hydrolyzing phospholipase C
      was observed in sarcolemmal membranes purified from hypothyroid hearts as
      compared to age-matched euthyroid controls. Following stimulation with 10 microM
      phenylephrine (in the presence of 10 microM atenolol), the increase of
      contractile parameters over baseline values was significantly higher in hypo-
      than euthyroid hearts, while the opposite occurred under beta-stimulation with
      0.1 microM isoproterenol. Interestingly, the increase in phenylephrine-mediated
      positive inotropy was accompanied by a significant increase in the sarcolemmal
      phospholipase C activity and in the inositol 1,4,5-trisphosphate content in
      hypothyroid as compared to euthyroid controls. Our results suggest that cardiac
      alpha(1)-adrenoceptor and its associated phosphoinositide signaling pathway may
      act as a reserve for catecholamine inotropic response in hypothyroidism, where
      the beta-adrenoceptors are compromised.

PMID- 16444592
TI  - Functional changes in bladder tissue from type III collagen-deficient mice.
AB  - OBJECTIVE: Collagen fibers impart tensile strength and transfer tension from
      bladder smooth muscle cells. We have previously shown that fibrotic bladders are
      characterized by an increased type III:type I collagen ratio. To determine the
      effect of decreased type III collagen on bladder function, type III collagen
      deficient mice (COL3A1) were studied physiologically. METHODS: Bladders from wild
      type (+/+) and heterozygous (+/-) COL3A1 mice were biochemically characterized to
      determine total collagen (hydroxyproline analysis) and collagen subtype
      concentration (cyanogen bromide digestion and ELISA). Alterations in collagen
      fiber diameter were assessed by electron microscopy. Bladder muscle strips were
      used to assess physiologic function. RESULTS: Hydroxyproline content decreased in
      heterozygous bladders, which had 50% less type III collagen. Wild-type bladders
      had a biphasic distribution of collagen fiber sizes, whereas heterozygous bladder
      collagen fibers spanned a broad range. Physiologically, there were no differences
      in contractile responses between wild-type and heterozygotes when stimulated with
      ATP, carbachol or KCl, indicating normal contraction via purinergic and
      muscarinic receptors, and in response to direct membrane depolarization. In
      contrast, tension generation in heterozygotes was decreased after field
      stimulation (FS), indicating decreased synaptic transmission. Length-tension
      studies showed that the heterozygote muscle strips generated less tension per
      unit length, indicating that they were more compliant than wild-type controls.
      CONCLUSIONS: Critical levels of type III collagen appear to be a requirement for
      normal bladder tension development and contraction. Our data show that a decrease
      in the type III:type I collagen ratio, and altered fiber size, results in a more
      compliant bladder with altered neurotransmitter function.

PMID- 16444593
TI  - Interrelations between oxidative stress and calcineurin in the attenuation of
      cardiac apoptosis by eugenol.
AB  - In view of the known involvement of oxidative stress and calcineurin (Ca(2+)
      calmodulin dependent protein phosphatase) in beta-Adrenergic stimulated events,
      we examined the influence of eugenol (an antioxidant generally regarded as safe
      by the Food and Agricultural Organization of the United Nations) on isoproterenol
      induced apoptosis in neonatal cardiomyocytes. In comparison to unstimulated
      controls, cardiomyocytes stimulated with 50 microM isoproterenol for 48 h
      demonstrated (a) increased intracellular Ca(2+) levels (b) oxidative stress
      involving enhanced reactive oxygen species, decreased GSH/GSSG ratio, enhanced
      lipid peroxidation, increased activities of superoxide dismutase and glutathione
      peroxidase (c) apoptosis, evidenced by increased number of annexin V/TUNEL
      positive cells, enhanced membrane fluidity, decreased mitochondrial membrane
      potential, increased activities of caspase 3 and 9 along with (d) increased
      calcineurin activity. Pre-incubation of cardiomyocytes with 100 microM eugenol
      for 1 h, followed by isoproterenol treatment for 48 h, led to reversal of
      enhanced intracellular Ca(2+) levels, oxidative stress, calcineurin activation
      and apoptosis caused by isoproterenol. In addition, similar treatment of
      cardiomyocytes with 10 nM FK506, a calcineurin inhibitor, could also attenuate
      isoproterenol-induced apoptosis. These results indicate the beneficial effects of
      eugenol in preventing cardiomyocyte apoptosis.

PMID- 16444594
TI  - Influence of selenium (antioxidant) on gliclazide induced hypoglycaemia/anti
      hyperglycaemia in normal/alloxan-induced diabetic rats.
AB  - Oxidative stress is involved in diabetes mellitus and its complications. Since
      diabetes is a stress-related disorder, supplementation with antioxidants may
      improve the condition. The purpose of this study is to know the effect of oral
      administration of selenium on blood glucose and its influence on gliclazide
      induced hypoglycaemia/antihyperglycaemia in normal and alloxan-induced diabetic
      rats. Albino rats of either sex were divided into three groups of six each. Group
      I/II/III were treated with selenium 1/2 TD (0.9 microg/200 g rat)/TD (1.8
      microg/200 g rat)/2TD (3.6 microg/200 g rat), respectively. Later group II was
      treated with gliclazide TD (1.44 mg/200 g rat)/selenium TD + gliclazide TD with a
      washout period of 1 week between the treatments. Diabetes was induced by alloxan
      monohydrate 100 mg/kg body weight i.p. A group of six rats showing fasting blood
      glucose levels ranging from 175-250 mg/dl were selected for the study. Rats were
      treated with selenium TD, gliclazide TD and selenium TD + gliclazide TD with a
      washout period of 1 week between the treatments. Selenium 1/2 TD and TD produced
      hypoglycaemia while 2TD produced hyperglycaemia. The combination of selenium TD
      with gliclazide TD, significantly enhanced the glucose lowering effect of
      gliclazide in normal and diabetic rats.

PMID- 16444595
TI  - Metallothionein-3 and neuronal nitric oxide synthase levels in brains from the
      Tg2576 mouse model of Alzheimer's disease.
AB  - Using antiserum against the recombinant isoform 3 of mouse brain metallothionein
      (MT3), the amount of MT3 protein was determined in whole brain homogenates from
      the Tg2576 transgenic mouse model of Alzheimer's Disease. Twenty-two month old
      transgenic positive mice showed a 27% decrease of MT3 normalized to the total
      protein in the extracts compared to same age, control transgenic negative mice.
      Metallothioneins bind seven molar equivalents of divalent metal ions per mole of
      protein so metal levels also were measured in these whole brain extracts using
      inductively coupled plasma atomic absorption (ICP-AA) spectrometry. No
      significant difference was observed for any metal assayed. Because neuronal
      nitric oxide synthase (nNOS) is involved in neurodegenerative disease and nitric
      oxide specifically interacts with MT3, the concentration and total nNOS activity
      also were evaluated. The transgenic positive mice showed a decrease of 28% in
      nNOS protein compared to the same age transgenic negative mice. Normalized to the
      amount of nNOS protein, total NOS activity was higher in the transgenic positive
      mice. These data showed that protein levels of both MT3 and nNOS were reduced in
      transgenic positive mice that show many characteristics of Alzheimer's Disease.
      In vitro studies suggested that MT3 was not a likely candidate for directly
      affecting nNOS activity in the brain.

PMID- 16444596
TI  - Synergistic interactions of ferulic acid with ascorbic acid: its cardioprotective
      role during isoproterenol induced myocardial infarction in rats.
AB  - Studies on the lipid peroxidation and antioxidant changes and their significance
      during myocardial injury have provided a new insight into the pathogenesis of
      heart disease. The heart failure subsequent to myocardial infarction may be
      associated with an antioxidant deficit as well as increased myocardial oxidative
      stress. The present study was designed to evaluate the effect of the combination
      of ferulic acid and ascorbic acid on antioxidant defense system and lipid
      peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats.
      Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2
      days resulted in a marked elevation in lipid peroxidation, serum marker enzymes
      (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous
      antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination
      of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body
      weight/day) orally for 6 days, significantly attenuated these changes when
      compared to the individual treatment groups. Histopathological observations were
      also in correlation with the biochemical parameters. Thus, ferulic acid and
      ascorbic acid significantly counteracted the pronounced oxidative stress effect
      of ISO by the inhibition of lipid peroxidation, restoration of antioxidant
      status, and myocardial marker enzymes levels. In conclusion, these findings
      indicate the synergistic protective effect of ferulic acid and ascorbic acid on
      lipid peroxidation and antioxidant defense system during ISO-induced myocardial
      infarction and associated oxidative stress in rats.

PMID- 16444597
TI  - Adverse effects of free fatty acid associated with increased oxidative stress in
      postischemic isolated rat hearts.
AB  - The mechanisms of the adverse effects of free fatty acids on the ischemic
      reperfused myocardium are not fully understood. Long-chain fatty acids, including
      palmitate, uncouple oxidative phosphorylation and should therefore promote the
      formation of oxygen-derived free radicals, with consequent adverse effects.
      Conversely, the antianginal agent trimetazidine (TMZ), known to inhibit cardiac
      fatty acid oxidation, could hypothetically lessen the formation of reactive
      oxygen species (ROS) and thus improve reperfusion mechanical function. Isolated
      perfused rat hearts underwent 30 min of total global ischemia followed by 30 min
      of reperfusion. Hearts were perfused with glucose 5.5 mmol/l or palmitate 1.5
      mmol/l with or without TMZ (100 micromol/l). Ascorbyl free radical (AFR) release
      during perfusion periods was measured by electron spin resonance as a marker of
      oxidative stress. Post-ischemic recovery in the palmitate group of heart was
      lower than in the glucose group with a marked rise in diastolic tension and
      reduction in left ventricular developed pressure (Glucose: 85 +/- 11 mmHg;
      Palmitate: 10 +/- 6 mmHg; p < 0.001). TMZ decreased diastolic tension in both
      glucose- and in palmitate-perfused hearts. Release of AFR within the first minute
      of reperfusion was greater in palmitate-perfused hearts and in hearts perfused
      with either substrate, this marker of oxidative stress was decreased by TMZ
      (expressed in arbitrary units/ml; respectively: 8.49 +/- 1.24 vs. 1.06 +/- 0.70 p
      < 0.05; 12.47 +/- 2.49 vs. 3.37 +/- 1.29 p < 0.05). Palmitate increased the
      formation of ROS and reperfusion contracture. TMZ, a potential inhibitor of
      palmitate-induced mitochondrial uncoupling, decreased the formation of free
      radicals and improved postischemic mechanical dysfunction. The novel conclusion
      is that adverse effects of fatty acids on ischemic-reperfusion injury may be
      mediated, at least in part, by oxygen-derived free radicals.

PMID- 16444598
TI  - Leptin blockade attenuates sodium excretion in saline-loaded normotensive rats.
AB  - Previous investigations in normotensive animals have demonstrated a marked
      natriuretic and diuretic response following the acute administration of
      supraphysiologic doses of synthetic leptin. However, the importance of endogenous
      leptin in the regulation of renal sodium and water balance is not yet defined.
      This study examined the hemodynamic and renal excretory effects of circulating
      leptin blockade with a specific polyclonal antibody in groups of normotensive,
      chronically saline-loaded Sprague-Dawley rats. In the experimental group (n =
      10), leptin antibody significantly decreased urinary sodium excretion and urinary
      flow by approximately 30% compared to the control rats (n = 10). Mean arterial
      pressure remained unchanged. Collectively, these results are interpreted to
      suggest that leptin is an important renal sodium-regulating factor under
      conditions of mild sodium and volume expansion.

PMID- 16444600
TI  - Kinetic characterization of Zinc transport process and its inhibition by Cadmium
      in isolated rat renal basolateral membrane vesicles: in vitro and in vivo
      studies.
AB  - We firstly characterized zinc uptake phenomenon across basolateral membrane
      vesicles (BLMVs) isolated from normal rat kidney. The process was found to be
      time, temperature, and substrate concentration dependent, and displayed
      saturability. Zn(2+) uptake was competitively inhibited in the presence of 2 mM
      Cd with Ki of 3.9 mM. Zinc uptake was also inhibited in the presence of
      sulfhydryl reacting compound suggesting involvement of [-]SH groups in the
      transport process. Further, to elucidate the effect of in vivo Cd on zinc
      transport in BLMVs, Cd nephrotoxicity was induced by subcutaneous administration
      of CdCl(2) at dose of 0.6 mg/kg/d for 5 days in a week for 12 weeks. An indolent
      renal failure developed in Cd exposed rats was accompanied with a significantly
      high urinary excretion of Cd(2+), Zn(2+) and proteins. The histopathology and
      electron microscopy of kidneys of Cd exposed rats documented changes of proximal
      tubular degeneration. Notably, Cd content in renal cortex of Cd exposed rats was
      215 microg/g tissue that was higher than the critical concentration of Cd in
      kidneys which was associated with significantly higher Zn and metallothionein
      (MT) contents. Zinc uptake in BLMVs isolated from kidneys of Cd exposed rats was
      significantly reduced. Further, kinetic studies revealed that decrease in zinc
      uptake synchronized with decrease in maximal velocity (V(max)) and increase in
      affinity constant which is suggestive of decreased number of active zinc
      transporters. Furthermore, conformational modulation of Zn transporter in BLM was
      further supported by observed variation in transition temperature for zinc
      transport in BLMVs isolated from Cd-exposed kidney.

PMID- 16444599
TI  - tNOX, an alternative target to COX-2 to explain the anticancer activities of non
      steroidal anti-inflammatory drugs (NSAIDS).
AB  - Our work has identified a cancer-specific, cell surface and growth-related quinol
      oxidase with both NADH oxidase and protein disulfide-thiol interchange
      activities, a member of the ECTO-NOX protein family designated tNOX. We provide
      evidence for tNOX as an alternative drug target to COX-2 to explain the
      anticancer activity of COX inhibitors. Non-steroidal anti-inflammatory drugs
      (NSAIDS), piroxicam, aspirin, ibuprofen, naproxen and celecoxib all specifically
      inhibited tNOX activity of HeLa (human cervical carcinoma) and BT-20 (human
      mammary carcinoma) cells (IC(50) in the nanomolar range) without effect on ECTO
      NOX activities of non-cancer MCF-10A mammary epithelial cells. With cancer cells,
      rofecoxib was less effective and two NSAIDS selective for COX-1 were without
      effect in inhibiting NOX activity. The IC(50) for inhibition of tNOX activity of
      HeLa cells and the IC(50) for inhibition of growth of HeLa cells in culture were
      closely correlated. The findings provide evidence for a new drug target to
      account for anticancer effects of NSAIDS that occur independent of COX-2.

PMID- 16444601
TI  - De-differentiation of primary human hepatocytes depends on the composition of
      specialized liver basement membrane.
AB  - Basement membrane (BM) is a highly specialized extracellular matrix (ECM), which
      is associated with epithelia and endothelia. BM provide epithelia with structural
      support and also regulate cell behavior. The liver contains a unique ECM within
      the space of Disse, which consists of basement membrane constituents as well as
      fibrillar ECM molecules. Changes in composition of this ECM are considered
      detrimental for viability of hepatocytes during progression of liver disease.
      Mouse tumor-derived BM preparations, such as Matrigel, which are commonly used as
      a model for BM in vitro, differ significantly in their composition from liver BM
      present in vivo. In order to gain further insights into the role of BM in the
      regulation of hepatocyte behavior in health and disease, we generated a liver
      derived basement membrane matrix (LBLM). LBLM allowed investigation of BM
      hepatocyte interactions in vitro. Here we report a novel approach of generating a
      liver-derived basement membrane matrix by separate isolation of type IV collagen,
      laminin, nidogen, and heparan sulfate proteoglycans, and subsequent
      reconstitution into a matrix-like gel. Adhesion of primary human hepatocytes to
      LBLM was increased and the rate of de-differentiation was decreased compared to
      hepatocyte cultivation on Matrigel or type I collagen matrix. Primary human
      hepatocytes maintained their differentiated epithelial phenotype on LBLM isolated
      from normal human livers for more than 21 days, whereas they de-differentiated
      rapidly on LBLM isolated from cirrhotic human livers. Normal human LBLM contains
      a unique isoform composition of type IV collagen, namely alpha1 (IV), alpha2(IV),
      alpha4(IV), and alpha6(IV) chains, whereas cirrhotic LBLM contains only
      alpha1(IV) and alpha2(IV) isoforms, albeit present in increased amounts. These
      findings suggest that the composition of liver basement membrane is important for
      the maintenance of hepatocyte viability and provide anti-de-differentiation
      clues.

PMID- 16444604
TI  - An uncontrolled trial of rituximab for antibody associated paraneoplastic
      neurological syndromes.
AB  - Anti-CD20 monoclonal antibody (rituximab) is effectively used in the treatment of
      B-cell lymphomas. Recent reports in the literature suggest that antibody
      associated autoimmune disorders may respond to rituximab. We therefore treated
      nine patients with anti-Hu or anti-Yo associated paraneoplastic neurological
      syndromes (PNS) with a maximum of four monthly IV infusions of rituximab
      (375mg/m(2)). In this uncontrolled, unblinded trial of rituximab, three patients
      improved > or =1 point on the Rankin Scale (RS). One patient with limbic
      encephalitis improved dramatically (RS from 5 to 1). Further studies of rituximab
      in autoantibody associated PNS are warranted.

PMID- 16444605
TI  - William Osler (1849-1919).

PMID- 16444602
TI  - Involvement of Rho-kinase in experimental vascular endothelial dysfunction.
AB  - The present study has been designed to investigate the effect of fasudil (Rho
      kinase inhibitor) in diabetes mellitus (DM) and hyperhomocyteinemia (HHcy)
      induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg(-1),
      i.v., once only) and methionine (1.7% w/w, p.o., daily for 4 weeks) were
      administered to rats to produce DM (serum glucose >140 mg dl(-1)) and HHcy (serum
      homocysteine >10 microM) respectively. VED was assessed using isolated aortic
      ring, electron microscopy of thoracic aorta, and serum concentration of
      nitrite/nitrate. Serum thiobarbituric acid reactive substances (TBARS)
      concentration was estimated to assess oxidative stress. Atorvastatin has been
      employed in the present study as standard agent to improve vascular endothelial
      dysfunction. Fasudil (15 mg kg(-1) and 30 mg kg(-1), p.o., daily) and
      atorvastatin (30 mg kg(-1), p.o., daily) treatments significantly attenuated
      increase in serum glucose and homocysteine but their concentrations remained
      markedly higher than sham control value. Fasudil and atorvastatin treatments
      markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine induced
      endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining,
      (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum
      TBARS. It may be concluded that fasudil prevented DM and HHcy-induced VED
      partially by decreasing serum glucose and homocysteine concentration due to
      inhibition of Rho-kinase. Moreover, inhibition of Rho-kinase by fasudil and
      consequent prevention of oxidative stress may have directly improved VED in
      diabetic and hyperhomocysteinemic rats. The Rho-kinase appears to be a pivotal
      target site involved in DM and HHcy-induced VED.

PMID- 16444619
TI  - Stent implantation for the unprotected left main coronary artery. The long-term
      outcome of 62 patients.
AB  - INTRODUCTION: Stent implantation for the unprotected left main coronary artery
      (ULMCA) is regarded as controversial and coronary heart disease with LMCA
      stenosis still remains a basic indication for bypass surgery. Although there is
      no doubt that the risk of stent implantation for LMCA lesions is low, there are
      still limited data on long-term outcomes. There have been no reports so far
      answering the question whether ULMCA stenting ensures adequate coronary blood
      flow in the vessel. AIM: Assessment of the effect of LMCA flow restoration with
      stenting on the coronary flow reserve assessed by an exercise test, as well as on
      left ventricular function and angina in patients followed for 12 months after the
      procedure. METHODS: The study population included 62 patients (17 women and 45
      men) aged 61.4+/-11.1 (35-84 years) who underwent coronary angioplasty with
      elective ULMCA stenting. In all patients, serial echocardiography (before and 1,
      3, 6, and 12 months after the procedure) and the exercise test according to the
      Bruce protocol (1, 3, 6, 12 months after the procedure) were carried out. Routine
      coronary angiography was performed 3 to 6 months after the procedure. Fifty-nine
      patients (95.2%) survived a 12-month period. In 24 (38.7%) patients major adverse
      cardiac events (MACE) occurred. In-stent restenosis was observed in 13 patients;
      in 11 of them repeated PCI was performed and 2 of them underwent CABG. One
      patient after repeated PCI required CABG. RESULTS: Severity of angina, evaluated
      according to the CCS scale, decreased significantly in the 12-month follow-up
      period as compared with the preprocedural period (p <0.00001). The mean baseline
      left ventricular ejection fraction was 51.6+/-12.5%. It increased to 53.8+/-12.8%
      (p <0.02) at 6 months and remained at this level at 12 months. The mean exercise
      test time was 7.0+/-3.4 minutes in the first month after ULMCA stenting, and in
      the sixth and the twelfth month of follow-up it increased to 7.6+/-3.4 minutes (p
      <0.002) and 7.8+/-3.2 minutes (p <0.05), respectively. The metabolic equivalent
      task (MET) value did not change significantly during the observation period.
      CONCLUSIONS: Restoration of the physiological blood flow in the unprotected left
      main coronary artery with stent implantation is associated with a significant
      reduction of angina, significant improvement of the left ventricular systolic
      function and preservation of exercise capacity in long-term follow-up.

PMID- 16444621
TI  - ST segment elevation in lead aVR and coronary artery lesions in patients with
      acute coronary syndrome.
AB  - INTRODUCTION: Recently, the prognostic value of ST segment elevation in lead aVR
      in acute coronary syndrome (ACS) and its relationship with significant stenosis
      of the left main coronary artery (LMCAS) and three-vessel disease have been
      highlighted. AIM: Analysis of the relationship between ST segment elevation
      observed in aVR lead and angiographic severity of coronary artery disease in
      patients with ACS. METHODS: The study involved 134 patients with ACS, including
      54 subjects with ST elevation in aVR (group A) and 80 patients without elevation
      of ST in the same lead (group B), aged 33-78 years, mean 59.9+/-9.7 years. The
      severity of coronary artery disease was compared between the two groups. The
      logistic regression model was used for the analysis of factors affecting ST
      segment in aVR, as well as LMCAS and three-vessel disease probability. RESULTS:
      In patients with ST elevation in aVR, three-vessel disease prevalence was two
      times higher (61.1% vs 35.0%; p <0.01), and LMCAS - three times higher (55.6% vs
      17.5%; p <0.000001) than in those without ST elevation in aVR. Factors
      independently associated with ST elevation in aVR were LMCAS (OR 6.1; 95% CI 2.62
      14.23; p <0.00005), ST segment elevation in V1 (OR 3.03; 95% CI 1.34-6.86; p
      <0.01) and diabetes (OR 2.89; 95% CI 1.17-7.15; p <0.05). The predictors of LMCAS
      were three-vessel disease and ST elevation in aVR, while the predictors of three
      vessel disease were: LMCAS, diabetes, male gender and history of myocardial
      infarction. CONCLUSIONS: Elevation of the ST segment in aVR in the setting of
      acute coronary syndrome identifies patients with severe coronary artery disease.
      Only left main coronary artery disease, however, remains independently associated
      with ST segment elevation in aVR. Three-vessel disease and the left main coronary
      artery stenosis equivalent are not independent predictors of ST segment elevation
      in aVR of standard electrocardiograms recorded in patients with acute coronary
      syndrome.

PMID- 16444623
TI  - Did favourable trends in food consumption observed in the 1984-2001 period
      contribute to the decrease in cardiovascular mortality? - Pol-MONICA Warsaw
      Project.
AB  - AIM: To compare food consumption trends (1984-2001) with cardiovascular mortality
      trends (1984-2002) in an adult population of right-bank Warsaw residents and
      establish the delay between dietary changes and mortality reduction. METHODS:
      Cardiovascular mortality rates for the 1984-2002 period, calculated based on the
      Central Statistical Office data and the results of individual evaluation of
      nutrition patterns in 4 independent Pol-MONICA cross-sectional studies (1984,
      1988, 1993 and 2001) were analysed. RESULTS: The cardiovascular mortality rate in
      right-bank Warsaw inhabitants tended to increase until 1991, and then a decline
      was observed -- in 2002 in comparison to 1991 the mortality rate in both genders
      decreased by over 50%. From 1984 to 2001 a significant decrease in the following
      dietary factors was found: total energy intake, dietary cholesterol, and Keys
      score reflecting atherogenicity of the diet and animal fats. In contrast trends
      of vegetable fats intake increased. The favourable changes in the dietary habits
      of Warsaw inhabitants were correlated with the reduction of cardiovascular
      mortality (R2 within the range of 0.35-0.95), and the strongest relationship
      between these facts occurred after 7 years. CONCLUSIONS: A positive tendency
      observed with respect to nutrition patterns of right-bank Warsaw inhabitants
      contributed to the reduction of cardiovascular mortality.

PMID- 16444625
TI  - Selective ablation or isolation of all pulmonary veins in atrial fibrillation --
      when and for whom?
AB  - INTRODUCTION: Targeted treatment of atrial fibrillation (AF) involves
      circumferential isolation of all pulmonary veins (PV) or isolation of electrical
      connections within their ostia. Only in some cases are the real localisation and
      number of triggering foci, the anatomy of venous ostia as well as the form of AF
      (paroxysmal, persistent, chronic, primary or secondary) taken into consideration.
      AIM: To compare the results of selective electrical isolation (1-3 PV ostia or
      ablation of a single focus in other veins or atrium) versus isolation of all
      pulmonary veins. METHODS: RF ablation was performed in eighty patients (51 men,
      29 women) with symptomatic, drug-refractory AF. Fifty-nine patients had
      paroxysmal AF (PAF), 16 persistent (AFpers), and 5 chronic AF (AFchro). Selective
      ablation was carried out in those patients who had detectable AF triggers during
      sinus rhythm -- supraventricular extrasystolic beats (SVEB) of 1 to 3
      morphologies (group I). Extended ablation -- isolation of all 4-5 PV -- was
      performed in patients with multiple SVEB morphologies and heterogeneous
      electrical connections within all PV (group II). Group I consisted of 60 patients
      (22 females) aged 46+/-14 years, whereas group II comprised 20 patients (7
      females) aged 52+/-13 years. In 24 patients (18 from group I and 6 from group II)
      with concomitant typical atrial flutter, an ablation line in the cavo-tricuspid
      isthmus was also performed. Long-term results were assessed 17+/-15.6 (4-105)
      months after the procedure based on routine ECG, ambulatory 24-hour ECG
      monitoring, clinical evaluation and regular phone calls. In patients with PAF,
      left atrial diameter <4.2 cm and evidence of successful ablation, antiarrhythmic
      agents were withheld. In patients with AFpers and AFchro, antiarrhythmic drugs
      were discontinued 3 to 6 months after successful ablation. RESULTS: Complete
      procedural success was achieved in 61 (76%) patients, and significant clinical
      improvement was observed in another 9 (11%) patients. Effective ablation
      significantly improved quality of life. In group I the procedure was entirely
      successful or a marked improvement was reported (single, transient palpitation
      episodes and/or atrial tachyarrhythmias lasting up to 30 seconds) in 54 (90%)
      patients. Among 48 (80%) patients with complete success, 25 (42%) did not receive
      any antiarrhythmic drugs during follow-up, 12 (20%) with arterial hypertension
      received beta-blockers, and 11 (18%) continued beta-blocker + class I
      antiarrhythmic drug. In another 6 (10%) patients a significant clinical
      improvement in arrhythmia control was observed. In Group II the procedure was
      fully effective or a significant improvement was observed in 16 (80%) patients.
      Among 13 (65%) patients with complete success, 5 (25%) did not require any
      antiarrhythmic drugs, 4 (20%) who had hypertension continued beta-blockers, and
      another 4 (20%) continued beta-blocker + I class antiarrhythmic drug. A
      significant clinical improvement of arrhythmia control was observed in another 3
      (15%) patients. CONCLUSIONS: In patients with a limited number of triggering foci
      and limited AF substrate, selective ablation effectively eliminates AF with a low
      risk of complications. Detailed electrophysiological assessment (standard ECG, 12
      lead Holter ECG monitoring and endocardial mapping) allows precise identification
      of this group of patients. In patients with chronic and persistent AF benefits
      occur with some delay which is associated with a delayed reversal of atrial
      remodelling.

PMID- 16444627
TI  - The relationship between T-wave polarity and clinical as well as angiographic
      findings in the early stage of acute myocardial infarction.
AB  - BACKGROUND: Restoration of a positive T-wave in the chronic stage of myocardial
      infarction (MI) is usually seen in patients with a non-Q-wave (non-transmural)
      MI, where a viable tissue is present. The causes and significance of a positive T
      wave in the early phase of acute MI are not clear. AIM: To investigate
      angiographic and clinical characteristics of patients with a positive T-wave in
      the early stage of acute MI. METHODS: We evaluated the clinical and angiographic
      data in relation to T-wave polarity in 188 patients with acute MI. Coronary risk
      factors, pre-infarction angina, CK-MB level, left ventricular ejection fraction
      and angiographic findings were analysed. Death, cardiogenic shock, ventricular
      tachycardia/fibrillation and high-degree atrioventricular block were regarded as
      in-hospital complications. All electrocardiograms were divided into two groups,
      according to the shape of the T-wave, as exhibiting a positive T-wave or negative
      T-wave. RESULTS: A positive T-wave was present in 30 (15.9%) patients. None of
      the patients with a positive T-wave had three-vessel disease compared with 21.5%
      of patients with a negative T-wave (p <0.04). In-hospital complication rates were
      similar in both groups. CONCLUSIONS: Patients with a positive T-wave in the early
      phase of acute MI have significantly less frequently three-vessel disease than
      patients with a negative T-wave.

PMID- 16444629
TI  - The influence of low-dose atorvastatin on lipid levels and endothelial vascular
      function in patients with significant coronary artery stenosis.
AB  - BACKGROUND: Hyperlipidaemia is a well-established risk factor of the progression
      of coronary artery disease (CAD). Statins such as atorvastatin, as lipid-lowering
      agents, can not only normalise serum lipid levels, but also may improve
      endothelial function, reduce vascular inflammation and enhance plaque stability.
      AIM: To evaluate the efficacy of a low-dose atorvastatin regimen (10 mg daily) in
      patients with CAD. METHODS: Seventy-nine patients with stable angina of II or III
      functional class and angiographically significant stenosis of coronary arteries
      (>70%) entered a 12-week treatment period with atorvastatin 10 mg/day. Lipid
      profile, which included total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and
      triglycerides (TG) were assessed at baseline and after treatment at week 12. In
      addition, flow-mediated vasodilatation (FMD) and nitrate-induced dilation (NID)
      of the brachial artery were measured before and after treatment. RESULTS: Among
      79 patients included in the study, in 54 (68%) the target TC value <5.0 mmol/l,
      and in 51 (65%) the LDL-C level <3.0 mmol/l were achieved. Atorvastatin decreased
      TC level by 31% (p<0.01), LDL-C level by 35% (p<0.01), TG level by 23% (p<0.01)
      and increased HDL-C level by 8% (p<0.01). FMD was increased by 61 % (p<0.01) and
      normalised in 88% of patients after 3-month therapy of atorvastatin. NID was
      increased by 16% (p<0.05). CONCLUSION: Low-dose treatment with atorvastatin (10
      mg daily) is effective in reducing blood lipids and is associated with the
      improvement of endothelial function in patients with CAD.

PMID- 16444631
TI  - The significance of cardiac surgery scars in adult patients with congenital heart
      disease.
AB  - BACKGROUND: Scars resulting from heart surgery mark patients for life, yet their
      effect on patients' well-being is unknown. AIM: To determine what spheres of life
      may be affected by surgical chest scarring. METHODS: A preliminary questionnaire
      asked 10 random patients at our adult congenital heart disease clinic to describe
      personal consequences (if any) of having a cardiac surgery scar. Results provided
      the basis to design another questionnaire which asked specific questions and
      attempted to rate the effect of scars on identified areas of concern. RESULTS:
      One hundred consecutive patients attending the clinic (53 males) aged 18 to 50
      (mean 27 years) participated. Sixty percent reported that the scar affected them
      less now than in adolescence. The body was perceived as disfigured by 58%. The
      scar was concealed by 48% of patients. Attention to the scar made 19% of patients
      feel negative, 58% neutral and 23% positive. Chest scarring was associated with
      decreased self-esteem in 20% and decreased self-confidence in 18% of patients.
      Patients reported less effect of chest scarring on their choice of career,
      success in life, friendships, sexual relationships and choice of recreation.
      Sixty-one percent reported a positive effect on appreciation of health.
      CONCLUSION: Scars resulting from heart surgery may have a considerable effect on
      patients' body image and several aspects of everyday life.

PMID- 16444633
TI  - [Recurrent restenosis in patient with single vessel coronary artery disease].
AB  - We present a patient with a single-vessel coronary artery disease, who during 5.5
      years underwent 6 coronary intervention procedures -- 3 stent implantations
      including one drug eluting stent -- TAXUS, 2 balloon coronary angioplasty
      procedures and CABG. The choice of the optimal therapeutic method in patients
      with single-vessel coronary artery disease is discussed.

PMID- 16444635
TI  - [Myocardial bridging of the left anterior descending coronary artery and
      dobutamine-induced left ventricular outflow tract gradient -- a case report].
AB  - We present a case of a 47-year-old patient with arterial hypertension and
      progressive ST segment changes with a T wave inversion during 2 years of
      observation. Coronary angiography showed myocardial bridging of LAD and no
      significant coronary artery stenosis. During subsequent two last years the
      patient was repeatedly hospitalised due to chest pain. During the last
      hospitalisation a dobutamine stress testing was performed which provoked an
      increased left ventricular outflow tract gradient. This finding may be attributed
      to an early phase of hypertrophic cardiomyopathy, or dobutamine specific
      phenomenon.

PMID- 16444636
TI  - [Normal coronary angiogram in patient with diagnosis of acute coronary syndrome
      with ST segment elevation. Was it possible to recognise acute pulmonary embolism
      earlier?].
AB  - A case of a 48 year old male scheduled for early invasive treatment of acute
      coronary syndrome with ST segment elevation is presented. Clinical suspicion of
      acute pulmonary embolism was undertaken because of normal coronary angiogram and
      was confirmed by pulmonary angiography. Differential diagnosis based on medical
      history, electrocardiogram and laboratory findings was discussed.

PMID- 16444637
TI  - [Acute myocardial infarction in a young patient with a primary antiphospholipid
      syndrome -- a case report].
AB  - A case of a 34 year old woman with antiphospholipid syndrome, admitted to our
      hospital due to acute myocardial infarction, is presented. She had a history of
      deep vein thrombosis, two miscarriages and ischaemic stroke. The patient
      underwent successful primary coronary angioplasty and was discharged home.
      Factors predisposing to arterial thrombosis and treatment options are discussed.

PMID- 16444638
TI  - [Rupture of the sinus of Valsalva aneurysm complicated by infective endocarditis 
      - diagnosis difficulties].
AB  - Aneurysm of the sinus of Valsalva is a rare congenital heart disease. It
      constitutes about 0.14%-1.5% of congenital heart surgery cases. Aneurysm of the
      sinus of Valsalva can be asymptomatic for many years. Only rupture of the sinus
      of Valsalva aneurysm leads to hemodynamic disturbances which in turn causes rapid
      deterioration of patient clinical condition. Some of the congenital heart
      diseases can be complicated by of infective endocarditis. This case report
      concerns the rupture of the sinus of Valsalva aneurysm in a 45 year old woman,
      which caused infective endocarditis on the tricuspid valve, which has been
      initially diagnosed as a complication of congenital heart disease in the form of
      the intraventricular defect.

PMID- 16444639
TI  - [Stress and low level of social support as a psychosocial risk factor of
      cardiovascular diseases].

PMID- 16444640
TI  - [Atrial fibrillation, heart failure and QT interval prolongation -- diastolic and
      therapeutic difficulties].
AB  - A case of a 51-year old female with persistent atrial fibrillation, decompensated
      heart failure and polymorphic ventricular tachycardia due to acquired long QT
      syndrome is presented. Difficulties in monitoring QT interval and factors
      associated with torsades de points are discussed.

PMID- 16444642
TI  - [Severe pulmonary hypertension caused by untreated mitral stenosis. It still
      happens in the XXI century].
AB  - We present a case of a 58 years old patient with extremely severe mitral
      stenosis. Several years ago she denied surgical treatment despite qualification
      by cardiologists. At present hospitalisation mitral valve area was calculated as
      0.5 cm(2) with systolic right ventricular systolic pressure of 125 mmHg. Right
      ventricle was hypertrophied and extremely enlarged as well as both atria.
      Surprisingly she was still in sinus rhythm and had no thrombi in the left atrium.
      Patient died before scheduled surgery because of cardiac decompensation and renal
      insufficiency.

PMID- 16444643
TI  - [Ablation of incisional right atrial tachycardia with critical region between
      surgical scar and crista terminalis in a patient with corrected transposition of
      great arteries after correction of Fallot-like pentalogy, Ebstein-like tricuspid
      valve anomaly and WPW syndrome].
AB  - In a 14 year old boy with corrected transposition of great arteries after
      correction of Fallot-like pentalogy, Ebstein-like tricuspid valve anomaly and WPW
      syndrome that was treated surgically, atrial tachycardia (AT) 260-280 ms was
      diagnosed and ablated. Due to earlier therapy it was impossible to insert
      catheters through femoral veins, and a subclavian and carotid veins access was
      used. The arrhythmia was a peri-incisional right AT. The isthmus was diagnosed
      with the use of entrainment pacing between a scar near VCI and the surgical
      incision along crista terminalis. Application in that region terminated AT and it
      was not inducible after the procedure.

PMID- 16444644
TI  - [Heart transplantation for the treatment of aortic dissection and concomitant
      advanced coronary arteriosclerosis].

PMID- 16444645
TI  - [Can beta-blockers become first-line therapy in chronic heart failure?].

PMID- 16444646
TI  - [The FIELD study raises questions on the role of fibrates in the cardiovascular
      prevention in diabetes].

PMID- 16444649
TI  - [Combined splint-packings in septoplastik and surgery of the inferior turbinate].

PMID- 16444650
TI  - [Comparison of two application forms for isotonic sodium-chloride solution in
      postoperative sinus-surgery wound care].
AB  - BACKGROUND: The recommended postoperative care after sinus-surgery is based on
      gentle removal of crusts, the regular moistening of the endonasal mucosa, and the
      application of ointments. The efficacy and the compliance of two different
      methods of mucosal irrigation are described in a patients series. METHODS: In a
      randomised study 50 patients who had undergone endoscopic sinus-surgery, 24
      patients using a nasal spray and 20 patients using manual irrigation were
      reviewed. The endonasal degree of obstruction was videotaped at four different
      locations (nasal floor, middle meatus, maxillary sinus ostium, ethmoidal system)
      on two different examinations. RESULTS: The only significantly reduced grade of
      obstruction was found in the ethmoidal system in the group using nasal spray. The
      results in the other locations showed no difference comparing both irrigation
      methods. The acception rate was higher in the group of nasal spray users.
      CONCLUSIONS: Nasal spray seems to be superior to manual irrigation in regard to
      postoperative wound conditioning, handling, and hygienic aspects.

PMID- 16444651
TI  - [Modern anesthesiologic concepts supporting paranasal sinus surgery].
AB  - BACKGROUND: Optimal vision is essential for successful endonasal sinus surgery.
      Beside topical vasoconstriction general anaesthesia can contribute to reduce
      intraoperative bleeding. METHODS AND RESULTS: For many years deliberate
      hypotension was used to prevent intraoperative bleeding. The intentional
      reduction of systolic blood pressure to 50-60 mm Hg was achieved by the use of
      Sodium Nitroprusside alone or in combination with other vasoactive agents.
      However, intraoperative bleeding is not affected by this technique unless the
      systolic blood pressure falls below 60 mm Hg which can cause serious side effects
      for the patient. Recently, there is growing evidence that not only systolic blood
      pressure but also a low heart rate (< 60 beats per minute) can minimize surgical
      bleeding. With the introduction of total intravenous anaesthesia (TIVA) by the
      use of Propofol and Remifentanyl an anaesthetic technique has been established
      which fulfils the haemodynamic requirements in endonasal sinus surgery in many
      regards. The inhibiting effects on the cardiovascular system of these drugs alone
      can lead to a reduced bleeding. TIVA allows the reduction of the systolic blood
      pressure to 60 mm Hg as well as the heart rate below 60 beats per minute. If
      necessary it can be supported by vasoactive agents of which betablockers have a
      theoretical advantage. CONCLUSION: For general anaesthesia in endonasal sinus
      surgery Sodium Nitroprusside is no longer recommended. Instead a TIVA using
      Propofol and Remifentanil should be used.

PMID- 16444652
TI  - [Endonasal measurement of mucociliary clearance at various locations in the nose:
      a new diagnostic tool for nasal function?].
AB  - INTRODUCTION: Mucociliary clearance is one of the major functions of the nasal
      epithelium. Limited information on the physiology or malfunction could up to now
      only be obtained by experimental investigations in vitro with cytological
      measurements of ciliary beat frequency or with extensive, time-consuming in-vivo
      tests. METHODS: We developed a new technique, which measures the transport
      capacity at various locations at the mucosa in the nose of a sitting patient with
      a short (30 sec) video-endoscopic examination. The velocity of a 500 microm TiO2
      microsphere as inert marker, which is placed on the mucosa region of interest, is
      measured by a vector-analytic calculation in mm/min. RESULTS: : We validated this
      technique in 20 subjects with measurements on the floor of the nose. The inter
      individual variance and variable transport speed at different locations as known
      from the literature could be confirmed. CONCLUSIONS: This technique allows for
      the first time to measure the mucociliary clearance at various locations inside
      the nose of a patient in a short and easy to perform procedure, which up to now
      necessitated extensive or experimental set-ups. Besides the establishment of a
      register of mucociliary clearance at various anatomical localisations inside the
      nose (olfactory epithelium, conchae, surrounding of the ostiae etc.), we intend
      to verify if this technique can be used as a new diagnostic tool to obtain a
      deeper insight into some pathologic alterations or uncharacteristic symptoms
      ("post-nasal-drip") or drug-effects in the nose and in the tracheo-bronchial
      system.

PMID- 16444654
TI  - [Evaluation of a new lid implant for rehabilitation of the paralyzed eye].
AB  - BACKGROUND: Since 1999 the platinum chain is being used as implant to correct
      lagophthalmos, which promises, due to its flexibility, lower postoperative
      complications. The lack of mandatory results reported in the literature, prompted
      us to survey all surgeons using the platinum chain in order to learn of the
      complications they had experienced. METHODS: A questionnaire was sent to 30
      surgeons to survey results and complications associated with the implantation of
      the platinum chain to treat lagophthalmos. Complications like contouring,
      migration and extrusion of the implant occurred. RESULTS: Complications observed
      were bulging of the implant in 12 cases (5,7 %), 4 migrations of the implant (1,9
      %), in 7 cases a frank extrusion (3,3 %), a ptosis of the upper eyelid in 8 cases
      (3,8 %), a corneal astigmatism in 3 cases (1,4 %) and in one case an infection of
      the upper eyelid (0,5 %). In 2 cases (0,9 %) the patients lamented a mechanical
      irritation of the upper eyelid. CONCLUSION: Implantation of eyelid weights is a
      straightforward and reversible procedure for the surgical therapy of
      lagophthalmos. Through the use of the platinum chain as implant the postoperative
      complications are to be regarded as small in total. With that the effectiveness
      of the procedure can be increased compared to rigid gold implants.

PMID- 16444653
TI  - [Treatment of sensorineural hearing loss in acute viral otitis media with
      intratympanic dexamethasone and hyaluronic acid in comparison with intravenous
      therapy].
AB  - BACKGROUND: Intratympanic dexamethasone with hyaluronic acid has shown to be an
      effective treatment of the inner ear damage in sudden hearing loss and Meniere's
      disease. It is not known yet if the same applies to the toxic inner ear damage in
      acute viral otitis media. PATIENTS: Retrospectively, 26 patients who suffered
      from acute viral otitis media with sensorineural hearing loss were examined with
      regard to the improvement of their inner ear hearing loss. Twelve patients were
      treated with intravenous therapy only, consisting of hydroxyethyl starch,
      pentoxifylline and prednisolone. Fourteen patients additionally received
      intratympanic injections, consisting of dexamethasone and hyaluronic acid once
      acute inflammatory changes subsided. The inner ear hearing loss was evaluated by
      means of standard bone-conduction audiometry. RESULTS: Neither local nor systemic
      side effects of the intratympanic injections occurred. During treatment no
      significant difference in the improvement of bone-conduction thresholds in any
      frequency was seen between the two groups. CONCLUSIONS: Intratympanic injections
      of dexamethasone with hyaluronic acid do not result in any additional benefit on
      the sensorineural hearing loss in acute viral otitis media compared to
      intravenous therapy alone. A reason might be the post inflammatory changes of the
      round window membrane or the toxic nature of the acute viral infection affecting
      the inner ear.

PMID- 16444655
TI  - [Infected parotid cyst as a cause of facial palsy].
AB  - BACKGROUND: Inflammatory processes are a rare cause of peripheral facial palsy.
      In most cases even massive infection does not lead to a loss of facial nerve
      function. In the literature, only 8 cases of facial paralysis associated with
      parotid cyst have been described. PATIENT AND RESULTS: We present a case of
      facial palsy caused by an inflamed cyst of the parotid gland. The patient was
      operated on with the diagnosis malignant parotid tumor. The pathological report
      showed a squamous epithelial cyst, massive lymphocytic infiltration. CONCLUSIONS:
      As a rule the combination parotid gland lesion and facial palsy is a sign of
      malignancy, clinicians should be aware that, on rare occasions, facial nerve
      dysfunction may result from benign parotid gland disease.

PMID- 16444656
TI  - [Middle-ear adenoma].
AB  - In our case we present a 47-year old female patient, who had a history of one
      year of right-sided recurrent ear pain without any signs of ear-infections. A
      computer tomography (CT) imaging was carried out. At the mid-modiolar level, the
      axial CT-scan showed a small contrast-enhancing density in the middle ear space.
      She refused further investigation until the ear-pain increased and slight hearing
      loss was present. Again, six months later a CT-scan was performed, and the
      hyperdense tissue formation engaged the entire middle ear cleft of the right
      temporal bone. Typical of MEA, no osteolytic signs were present; the skull-base
      was intact, the air-cell system of the temporal bone showed no osteolysis or
      deficiency. In the case presented here, we show a MEA which has filled the middle
      ear with fluid retention in the mastoid with absent destruction of any structure
      clinically resulting in ear pain and slight conductive hearing loss. These
      lesions are contrast-enhancing on CT and on magnetic resonance imaging (MRI) have
      brain-like signal intensity T2-weighted images. In this case, the lesion was
      exenterated.

PMID- 16444657
TI  - [Patient with antithrombotic medication. Which do bleedings or preoperative?].
AB  - Antithrombotic medication can be performed by means of heparins (non-fractionated
      heparin, low molecular heparins) or the pentasaccharide Fondaparinux as well as
      with oral vitamin K antagonists. The use of a low molecular heparin is initially
      recommended for the sake of practicability and safety in case of patients
      suffering from deep venous thrombosis of the leg and pelvis with subsequent long
      term oral medication using a vitamin K antagonist (Marcumar) for anticoagulation.
      The most frequent indications for long-term anticoagulation are deep leg and
      pelvis thromboses, pulmonary embolism with atrial fibrillation, artificial
      prosthetic valves and open oval foramen with ischaemic cerebral infarction. In
      case of patients with chronic atrial fibrillation it is expedient to initiate
      permanent anticoagulation according to a risk score. For the purpose of
      controlling oral anticoagulation it is recommended to employ the INR value in
      place of Quick's value because these data are better comparable. In case of
      atherothrombotic diseases secondary prevention will always indicate
      administration of a thrombocyte aggregation inhibitor. In such cases
      acetylsalicylic acid is recommended as the standard preparation.

PMID- 16444659
TI  - Botanical therapies in chronic fatigue.
AB  - Chronic fatigue often occurs in aging and in various neurological, psychiatric
      and systemic diseases. The available therapies in modern medicine are limited.
      The exploration of potential alternative therapies from traditional medicine is
      reviewed, as there are several botanicals with experimental evidence of efficacy
      based on animal models and clinical studies.

PMID- 16444660
TI  - Anxiolytic effects of a combination of Melissa officinalis and Valeriana
      officinalis during laboratory induced stress.
AB  - OBJECTIVE: Melissa officinalis (lemon balm) and Valeriana officinalis (valerian)
      have been used both traditionally and contemporaneously as mild sedatives,
      anxiolytics and hypnotics. Recent research has suggested that both may attenuate
      laboratory induced stress. As the two herbs are most often sold in combination
      with each other the current study assessed the anxiolytic properties of such a
      combination during laboratory-induced stress. METHODS: In this double-blind,
      placebo-controlled, randomized, balanced cross-over experiment, 24 healthy
      volunteers received three separate single doses (600 mg, 1200 mg, 1800 mg) of a
      standardized product containing M. officinalis and V. officinalis extracts, plus
      a placebo, on separate days separated by a 7 day wash out period. Modulation of
      mood and anxiety were assessed during pre-dose and 1 h, 3 h and 6 h post-dose
      completions of a 20 min version of the Defined Intensity Stressor Simulation
      (DISS) battery. Cognitive performance on the four concurrent tasks of the battery
      was also assessed. RESULTS: The results showed that the 600 mg dose of the
      combination ameliorated the negative effects of the DISS on ratings of anxiety.
      However, the highest dose (1800 mg) showed an increase in anxiety that was less
      marked but which reached significance during one testing session. In addition,
      all three doses led to decrements in performance on the Stroop task module within
      the battery, and the two lower doses led to decrements on the overall score
      generated on the DISS battery. CONCLUSIONS: These results suggest that a
      combination of Melissa officinalis and Valeriana officinalis possesses anxiolytic
      properties that deserve further investigation.

PMID- 16444661
TI  - Evaluation of anticancer activity of the alkaloid fraction of Alstonia scholaris
      (Sapthaparna) in vitro and in vivo.
AB  - The anticancer effect of various doses of an alkaloid fraction of Sapthaparna,
      Alstonia scholaris (ASERS), was studied in vitro in cultured human neoplastic
      cell lines (HeLa, HepG(2), HL60, KB and MCF-7) and in Ehrlich ascites carcinoma
      bearing mice. Treatment of HeLa cells with 25 microg/mL ASERS resulted in a time
      dependent increase in the antineoplastic activity and the greatest activity was
      observed when the cells were exposed to ASERS for 24 h. However, exposure of
      cells to ASERS for 4 h resulted in 25% viable cells and hence this time interval
      was considered to be the optimum time for treatment and further studies were
      carried out using this time. Treatment of various cells with ASERS resulted in a
      concentration dependent decline in the viable cells and a nadir was reached at
      200 microg/mL in all the cell lines studied. The IC50 was found to be 5.53, 25,
      11.16, 10 and 29.76 microg/mL for HeLa, HePG2, HL60, KB and MCF-7 cells,
      respectively. Similarly, administration of ASERS, once daily for 9 consecutive
      days to the tumor bearing mice caused a dose dependent remission of the tumor up
      to 240 mg/kg body weight, where the greatest antitumor effect was observed. Since
      240 mg/kg ASERS showed toxic manifestations, the next lower dose of 210 mg/kg was
      considered as the best effective dose, in which 20% of the animals survived up to
      120 days post-tumor-cell inoculation as against no survivors in the saline
      treated control group. The ASERS treatment resulted in a dose dependent elevation
      in the median survival time (MST) and the average survival time (AST) up to 240
      mg/kg ASERS and declined thereafter. The surviving animals were healthy and
      disease free. The effect of ASERS was better than cyclophosphamide, which was
      used as a positive control, where all the animals succumbed to death by 40 days
      and the MST and AST were 19.5 and 18.3 days, respectively. The effective dose of
      210 mg of ASERS was 3/10 of the LD50 dose, which increased the MST and AST up to
      54 and 49.5 days, respectively.

PMID- 16444662
TI  - Protective effect of selected flavonoids on in vitro daunorubicin-induced
      cardiotoxicity.
AB  - Flavonoids are an ubiquitous group of polyphenolic substances with varied
      chemical structures present in foods of plant origin and act as free radical
      scavenging and chelating agents with a variety of biological activities. Using a
      model of spontaneously beating, cultured adult rat cardiomyocytes, this study
      examined the cardioprotective role of quercetin, naringenin, pycnogenol and a
      model antioxidant, trolox, against daunorubicin-induced toxicity. Cardiomyocyte
      protection was assessed by MTT test and extracellular lactate dehydrogenase
      detection. Protection of cardiomyocytes was concentration/dose dependent for
      quercetin > naringenin > pycnogenol > trolox. Quercetin (10(-4)-10(-6) mol/L)
      after 24 h of co-incubation with daunorubicin significantly increased the
      cardiomyocyte survival in all tested concentrations (p < 0.001). The
      cytoprotective effect of naringenin (10(-4)-10(-6) mol/L) was similar to those of
      quercetin (p < 0.001 and p < 0.01, respectively). Pycnogenol was the least
      effective of the flavonoids studied. On the other hand, all tested flavonoids had
      significantly better protective effects than trolox. The leakage of lactate
      dehydrogenase induced by daunorubicin was also prevented by the studied compounds
      and was in accordance with their cytoprotective activity.

PMID- 16444663
TI  - An in vitro study of the protective effect of the flavonoid silydianin against
      reactive oxygen species.
AB  - The inhibitory effect of silydianin, an active constituent of Silybium marianum,
      on the in vitro production and release of oxidative products has been examined.
      Polymorphonuclear neutrophils (PMNs) play a primary role in the initiation and
      propagation of inflammatory responses. Their apoptosis is a major mechanism
      associated with the resolution of inflammatory reactions. Neutrophils were
      assessed for caspase-3 activity, the rst step in the execution phase of
      apoptosis. When cells were cultured with 100 microM silydianin for 24 h, caspase
      3 was activated. Induction of apoptosis by silydianin was accompanied by a
      decrease in luminol-enhanced chemiluminescence as well as superoxide radical (O2*
      ) release in freshly isolated cells and lipid peroxidation in mouse spleen
      microsomes. No significant effect of silydianin on PMN hydrogen peroxide
      production evaluated by a flow cytometric dichlorofluorescin oxidation assay was
      found. Such results indicate a possible antiinflammatory activity for silydianin,
      which regulates caspase-3 activation, affects cell membranes and acts as a free
      radical scavenger.

PMID- 16444664
TI  - Mangifera indica L. extract (Vimang) inhibits 2-deoxyribose damage induced by Fe
      (III) plus ascorbate.
AB  - Vimang is an aqueous extract of selected species of Mangifera indica L, used in
      Cuba as a nutritional antioxidant supplement. Many in vitro and in vivo models of
      oxidative stress have been used to elucidate the antioxidant mechanisms of this
      extract. To further characterize the mechanism of Vimang action, its effect on
      the degradation of 2-deoxyribose induced by Fe (III)-EDTA plus ascorbate or plus
      hypoxanthine/xanthine oxidase was studied. Vimang was shown to be a potent
      inhibitor of 2-deoxyribose degradation mediated by Fe (III)-EDTA plus ascorbate
      or superoxide (O2-). The results revealed that Vimang, at concentrations higher
      than 50 microM mangiferin equivalent, was equally effective in preventing
      degradation of both 15 mM and 1.5 mM 2-deoxyribose. At a fixed Fe (III)
      concentration, increasing the concentration of ligands (either EDTA or citrate)
      caused a significant reduction in the protective effects of Vimang. When
      ascorbate was replaced by O2- (formed by hypoxanthine and xanthine oxidase) the
      protective efficiency of Vimang was also inversely related to EDTA concentration.
      The results strongly indicate that Vimang does not block 2-deoxyribose
      degradation by simply trapping *OH radicals. Rather, Vimang seems to act as an
      antioxidant by complexing iron ions, rendering them inactive or poorly active in
      the Fenton reaction.

PMID- 16444665
TI  - Green tea (Camellia sinensis) extract ameliorates endotoxin induced sickness
      behavior and liver damage in rats.
AB  - Immune activation, either by cytokines or endotoxin, elicits a constellation of
      nonspecific symptoms such as weakness, malaise, listlessness, fatigue, adipsia,
      anorexia, depression and anxiety collectively termed as sickness behavior.
      Further, endotoxin administration in animals has been implicated in the
      pathogenesis of many types of liver disease. Green tea, a common household drink,
      is rich in antioxidant polyphenols demonstrating inhibitory effects on cytokine
      production. The present study was designed to investigate the effect of chronic
      treatment of green tea extract (GTE) on lipopolysaccharide (LPS)-induced sickness
      behavior and liver damage in rats. The hypothesis was tested through the analysis
      of LPS-induced behavioral changes in rats, in plus maze and open field paradigms.
      Other parameters such as feeding and water consumption, weight loss and organ
      weight index were also estimated. Liver function tests were conducted to
      investigate the effect of GTE supplementation on LPS-induced hepatic dysfunction.
      The results of the study demonstrated that GTE significantly attenuated LPS
      induced sickness behavior as well as hepatic damage either by its antioxidant
      activity or by inhibiting LPS induced cytokine production in rats.

PMID- 16444666
TI  - The antioxidant activity of a triterpenoid glycoside isolated from the berries of
      Hedera colchica: 3-O-(beta-D-glucopyranosyl)-hederagenin.
AB  - The antioxidant activity of a triterpenoid glycoside [3-O-(beta-D-glucopyranosyl)
      hederagenin; OGH] isolated from the berries of Hedera colchica, an ivy species
      endemic in Georgia, was investigated. The antioxidant properties of OGH were
      evaluated using different antioxidant assays: 1,1-diphenyl-2-picryl-hydrazyl free
      radical (DPPH.) scavenging, total antioxidant activity, reducing power,
      superoxide anion radical (O2*-)) scavenging, hydrogen peroxide (H2O2) scavenging
      and metal chelating activities. The total antioxidant activity was measured
      according to the ferric thiocyanate method. alpha-Tocopherol and trolox, a water
      soluble analogue of tocopherol, were used as reference antioxidant compounds. At
      a 30 microg/mL concentration, the inhibitory effects of OGH on the peroxidation
      of linoleic acid emulsion was found to be 95.3%, whereas alpha-tocopherol and
      trolox exhibited 88.8% and 86.2% inhibition of peroxidation in the system,
      respectively. In addition, OGH had effective DPPH. scavenging, superoxide anion
      radical scavenging, hydrogen peroxide scavenging, total reducing power and metal
      chelation of ferrous ions activities. These various antioxidant activities were
      compared with alpha-tocopherol and trolox.

PMID- 16444667
TI  - Effects of extracts and tannins from Arbutus unedo leaves on rat platelet
      aggregation.
AB  - Many cardiovascular diseases such as arterial hypertension are associated with an
      increase in blood platelet activity. Arbutus unedo (Ericaceae) is a medicinal
      plant reputed to treat arterial hypertension, so the present study was undertaken
      in order to determine the antiaggregant effect. The crude aqueous extract showed
      an inhibition of thrombin-induced platelet aggregation (IC50 = 1.8 +/- 0.09 g/L,
      n = 10). The subsequent extraction of Arbutus unedo leaves by successive solvents
      showed that the methanol and ethyl acetate extracts accounted for most of the
      antiaggregant activity (IC50 = 0.7 +/- 0.08, n = 9; 0.6 +/- 0.05; n = 9,
      respectively). The tannins isolated from the methanol extract exhibited a strong
      antiplatelet effect (% of inhibition = 75.3 +/- 1.4, n = 8) and may be the major
      chemical compounds responsible for this action. Our results support the
      traditional use of this plant in the preventive or therapeutic treatment of
      platelet aggregation linked to arterial hypertension.

PMID- 16444668
TI  - Effect of Withania somnifera root extract on reserpine-induced orofacial
      dyskinesia and cognitive dysfunction.
AB  - Tardive dyskinesia is one of the major side effects of long-term neuroleptic
      treatment. The pathophysiology of this disabling and commonly irreversible
      movement disorder is still obscure. Vacuous chewing movements in rats are widely
      accepted as an animal model of tardive dyskinesia. Oxidative stress and products
      of lipid peroxidation are implicated in the pathophysiology of tardive
      dyskinesia. Repeated treatment with reserpine (1.0 mg/kg) on alternate days for a
      period of 5 days (days 1, 3 and 5) significantly induced vacuous chewing
      movements and tongue protrusions in rats. Chronic treatment with Withania
      somnifera root extract (Ws) for a period of 4 weeks to reserpine treated animals
      significantly and dose dependently (50 and 100 mg/kg) reduced the reserpine
      induced vacuous chewing movements and tongue protrusions. Reserpine treated
      animals also showed poor retention of memory in the elevated plus maze task
      paradigm. Chronic Ws administration significantly reversed reserpine-induced
      retention deficits. Biochemical analysis revealed that chronic reserpine
      treatment significantly induced lipid peroxidation and decreased the glutathione
      (GSH) levels in the brains of rats. Chronic reserpine treated rats showed
      decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD) and
      catalase. Chronic administration of Ws root extract dose dependently (50 and 100
      mg/kg) and significantly reduced the lipid peroxidation and restored the
      decreased glutathione levels by chronic reserpine treatment. It also
      significantly reversed the reserpine-induced decrease in brain SOD and catalase
      levels in rats. The major findings of the present study indicate that oxidative
      stress might play an important role in the pathophysiology of reserpine-induced
      abnormal oral movements. In conclusion, Withania somnifera root extract could be
      a useful drug for the treatment of drug-induced dyskinesia.

PMID- 16444669
TI  - Echinacea extracts modulate the pattern of chemokine and cytokine secretion in
      rhinovirus-infected and uninfected epithelial cells.
AB  - Extracts of Echinacea purpurea are among the most widely used herbal medicines
      throughout Europe and North America for the prevention or treatment of common
      cold, coughs, bronchitis and other upper respiratory infections. Popular
      preparations include expressed juice from the aerial parts of the plant (which
      contain polysaccharides) and alcoholic tinctures from roots (containing caffeic
      acid derivatives and alkylamides). Since immune modulation has been reported for
      similar extracts, cytokine antibody arrays were used to investigate the changes
      in the pro-inflammatory cytokines and chemokines released from a cultured line of
      human bronchial epithelial cells exposed to Rhinovirus 14 and two different
      chemically characterized Echinacea extracts. Virus infection stimulated the
      release of at least 31 cytokine-related molecules, including several important
      chemokines known to attract inflammatory cells. Most of these effects were
      reversed by simultaneous exposure to either of the two Echinacea extracts,
      although the patterns of response were different for the two extracts. These
      results could explain the antiinflammatory properties of Echinacea extracts.
      Furthermore, a number of these cytokines were stimulated by the same Echinacea
      preparations in uninfected cells. These observations therefore provide support
      for the alleged beneficial uses of Echinacea extracts.

PMID- 16444670
TI  - Antibacterial activity of components from Lomatium californicum.
AB  - The isolation, characterization and bioactivity testing of compounds from
      Lomatium californicum (Nutt.) are described. Ethyl acetate and hexane extracts of
      the roots of L. californicum were subjected to vacuum liquid chromatography
      (VLC), flash column chromatography (FCC) and separation by normal- and reverse
      phase high-performance liquid chromatography (HPLC). Six compounds were isolated
      successfully and characterized by 1D and 2D nuclear magnetic resonance (NMR)
      experimentation. The bioactivity of the known compounds (+)-falcarindiol,
      coniferyl ferulate, ferulic acid and (Z)-ligustilide were confirmed against the
      Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. The known
      compounds senkyunolide I and trans-neocnidilide were also isolated but in too
      small a quantity for similar testing.

PMID- 16444671
TI  - Effects of two Prunella species on lymphocyte proliferation and nitric oxide
      production.
AB  - Water extracts of Prunella vulgaris and P. laciniata have been investigated for
      their immunomodulatory and antiinflammatory activities concerning their effect on
      the mitogenic response of murine splenocytes and nitric oxide production by
      murine peritoneal macrophages in vitro. It was found that both extracts
      stimulated the proliferation of T-lymphocytes and suppressed NO production in
      lipopolysaccharide-stimulated macrophages dose dependently without any
      cytotoxicity.

PMID- 16444672
TI  - Isolation of the active compound in Mauria heterophylla, a Peruvian plant with
      antibacterial activity.
AB  - A fraction from the ethanol extract of the Peruvian medicinal plant Mauria
      heterophylla (Anacardiaceae) showed antibacterial activity against Escherichia
      coli 35992, Staphylococcus aureus 20213 and Pseudomonas aeruginosa 15442. Further
      fractionation led to the isolation and characterization of ethyl gallate as the
      antibacterial active compound.

PMID- 16444673
TI  - Antibacterial activity of plant extracts from azuki beans (Vigna angularis) in
      vitro.
AB  - This study was undertaken to examine the antimicrobial property of azuki beans
      (Vigna angularis). The water extracts of green, black and red colored azuki beans
      showed antibacterial effects against Staphylococcus aureus, Aeromonas hydrophila
      and Vibrio parahaemolyticus. In contrast, the extract of white azuki beans showed
      no inhibition towards any of the microorganisms examined. The extracts of colored
      azuki beans contained larger amounts of polyphenols including proanthocyanidins
      than the extracts of white azuki beans. The counts of S. aureus cells, inoculated
      in the medium containing the extracts of colored azuki beans, were significantly
      reduced in comparison with those of control and white azuki beans after 24 h (p <
      0.05). These results suggest that polyphenols including proanthocyanidins in
      colored azuki beans may be responsible for their antibacterial activity.

PMID- 16444674
TI  - Bves, a member of the Popeye domain-containing gene family.
AB  - Bves was discovered through subtractive screens designed to identify heart
      enriched transcripts. Bves is a transmembrane protein that possesses a highly
      conserved structure among species of the animal kingdom. Various approaches have
      been used to elucidate the expression pattern of Bves mRNA and protein as well as
      its function in developing and mature organisms. Emerging evidence indicates that
      this protein is present in muscle and epithelia of developing embryos and the
      adult. In vitro functional studies predict a role in cell-cell interaction and/or
      adhesion. In vivo analysis of protein function is very limited at present, but
      recent work in Xenopus supports the importance of Bves in epithelial integrity.
      Presented in this review is a compilation of published findings concerning Bves
      gene and protein characteristics, expression patterns in embryos and cells, and
      functional significance as determined thus far. Presently, the literature
      supports a hypothesis that Bves is essential to the junctional architecture of
      muscle and epithelial cell types. Although there remain aspects of Bves
      structure, expression, and function that are not completely resolved, now is an
      appropriate time to summarize current knowledge about this protein, the remaining
      questions, and what its potential role in development might be. This review will
      serve as a departure point for others who become interested in the study of this
      highly conserved protein.

PMID- 16444675
TI  - Evaluation of semi-quantitative scoring system for metaiodobenzylguanidine (mIBG)
      scans in patients with relapsed neuroblastoma.
AB  - BACKGROUND: The purpose of this study was to determine the accuracy of two semi
      quantitative scoring systems to assess response to (131)I-metaiodobenzylguanidine
      (mIBG) therapy in recurrent neuroblastoma. PROCEDURES: Diagnostic mIBG scan pairs
      (n = 57) were collected for patients who underwent (131)I-mIBG therapy for
      relapsed neuroblastoma. Two scoring systems were designated: Method 1, which
      divided the body into nine segments to view osteomedullary lesions with an
      additional tenth segment to assess soft tissue involvement; and Method 2, which
      divided the body into seven segments without a corresponding compartment for soft
      tissue involvement. Four nuclear medicine physicians independently assigned
      extension and intensity scores utilizing both methods, and separately recorded
      their impression of whether the post-therapy scan had improved, not changed, or
      worsened. Inter- and intra-observer concordance and correlation with overall
      response and progression-free survival (PFS) were performed. RESULTS: Method 1
      produced the highest inter-observer concordance and was used to calculate the
      relative extension scores (post-therapy score divided by pre-therapy score),
      which correlated significantly with overall response. Patients who achieved
      complete response (CR) or partial response (PR) (n = 21) had lower relative
      extension scores, compared to those without response (P < 0.001). The readers'
      overall impression associated highly (P < 0.001) with the relative extension
      scores though results were less quantitative. Concordance was higher if initial
      scores were >5. Relative extension score did not predict PFS. CONCLUSION: Semi
      quantitative scoring of mIBG scans provides a more reliable method of assessing
      response in patients with relapsed neuroblastoma than qualitative impression. The
      reproducibility and high inter-observer concordance makes mIBG score an important
      component of overall response criteria in patients with recurrent neuroblastoma.

PMID- 16444677
TI  - Successful treatment of refractory chronic disseminated candidiasis after
      prolonged administration of caspofungin in a child with acute myeloid leukemia.
AB  - This report documents the clinical activity of caspofungin in a 13-year-old girl
      with acute myeloid leukemia (AML) and chronic disseminated candidiasis (CDC),
      refractory to amphotericin B and fluconazole. Caspofungin was started at 50 mg/d
      resulting in a temporary response. With no further clinical improvement and
      radiological progress after 2 months of therapy, the dose of caspofungin was
      increased to 100 mg/d, leading to a sustained clinical response. Therapy was
      given for a total of 12 months and had no attributable adverse effects. This
      approach resulted in successful treatment of refractory CDC with caspofungin.

PMID- 16444678
TI  - Intraocular Langerhans cell histiocytosis in a neonate resulting in bilateral
      loss of vision.
AB  - Intraocular involvement in Langerhans cell histiocytosis (LCH) is rare. We
      describe the case of a neonate with congenital disseminated LCH involving skin,
      liver, spleen, and intraocular structures including uvea and retina. Early and
      aggressive treatment according to the LCH-II treatment protocol was administered
      and resulted in remission of the disease. However, despite close follow-up and
      additional local treatment, involvement of intraocular structures resulted in
      severe long-term ophthalmological sequelae including complete bilateral loss of
      vision.

PMID- 16444679
TI  - A digital micro-mirror device-based system for the microfabrication of complex,
      spatially patterned tissue engineering scaffolds.
AB  - Our ability to create precise, pre-designed, spatially patterned biochemical and
      physical microenvironments inside polymer scaffolds could provide a powerful tool
      in studying progenitor cell behavior and differentiation under biomimetic, three
      dimensional (3D) culture conditions. We have developed a simple and fast, layer
      by-layer microstereolithography system consisting of an ultra-violet light
      source, a digital micro-mirror masking device, and a conventional computer
      projector, that allows fabrication of complex internal features along with
      precise spatial distribution of biological factors inside a single scaffold.
      Photo-crosslinkable poly(ethylene glycol) diacrylates were used as the scaffold
      material, and murine bone marrow-derived cells were successfully encapsulated or
      seeded on fibronectin-functionalized scaffolds. Fluorescently-labeled polystyrene
      microparticles were used to show the capability of this system to create
      scaffolds with complex internal architectures and spatial patterns. We
      demonstrate that precisely controlled pore size and shapes can be easily
      fabricated using a simple, computer-aided process. Our results further indicate
      that multi-layered scaffolds with spatially distributed factors in the same layer
      or across different layers can be efficiently manufactured using this technique.
      These microfabricated scaffolds are conducive for osteogenic differentiation of
      marrow-derived stem cells, as indicated by efficient matrix mineralization.

PMID- 16444680
TI  - Simultaneous determination of 109 pesticides in unpolished rice by a combination
      of gel permeation chromatography and Florisil column purification, and gas
      chromatography/mass spectrometry.
AB  - A multi-residue method is described for the simultaneous analysis of 109
      pesticides with different properties in unpolished rice. The range covers
      organophosphorus, organochlorine, carbamate, and synthetic pyrethroid pesticides.
      The pesticides were extracted from the sample using ethyl acetate. Most higher
      molecular weight components such as lipids in the co-extractives were removed by
      gel permeation chromatography (GPC) with a Bio-bead SX-3 column. A Florisil
      column with ethyl acetate/hexane as the eluting solvents was used for further
      cleanup. The pesticides were finally simultaneously determined by gas
      chromatography/mass spectrometry (GC/MS) in selective ion monitoring (SIM) mode.
      The average recoveries for most pesticides (spiked level 0.02, 0.1 and 1
      microg/g) ranged from 70% to 110%, the relative standard deviation (RSD) was
      below 20% in every case, and the limit of detection (LOD) varied from 1 to 20
      ng/g.

PMID- 16444681
TI  - A new approach for evaluating carryover and its influence on quantitation in high
      performance liquid chromatography and tandem mass spectrometry assay.
AB  - In a high-performance liquid chromatography (HPLC)-based analytical method,
      carryover denotes one type of systematic error that is derived from a preceding
      sample and introduced into the next sample. For typical bioanalytical method
      development, a significant amount of time and resources are spent on reducing
      carryover for some analytes. In this paper, the statistical characteristics of
      carryover were analyzed based on the experimental results. The relative carryover
      (RC), defined as the peak area ratio of a blank sample to the preceding sample,
      was constant for the analyte and independent of the concentration of the
      preceding sample. The influence of carryover on the quantitation of the next
      injected sample or the 'following' sample was proportional to the concentration
      ratio of two consecutive samples and the relative carryover. Based on these
      experiments and analyses, the influence of carryover on the quantitation of
      unknown samples in an HPLC assay can be evaluated by the estimated carryover
      influence (ECI), which is the product of the relative carryover and the
      concentration ratio. This new approach provides a quantitative estimation for the
      influence of carryover on the quantitation of the unknown sample, and removes the
      limit put on the dynamic range of the assay by the current criterion of
      carryover. In general, if the relative standard deviation (RSD) of a validated
      bioanalytical method is less than 10%, the carryover will not have a significant
      effect on the accuracy of the assay when the estimated carryover influence is
      less than 5%.

PMID- 16444682
TI  - Enterococcus faecalis-mediated biomineralized biofilm formation on root canal
      dentine in vitro.
AB  - Enterococcus faecalis is the most predominant bacteria in teeth with failed root
      canal therapy and is found to survive harsh conditions prevailing in the root
      canals of endodontically treated teeth. This study aims to investigate the
      interaction between E. faecalis and root canal dentine substrate. Towards this
      end, tooth specimens were prepared and divided into two groups. The tooth
      specimens in group 1 were incubated with E. faecalis for periods of 2-, 4-, and 6
      week intervals and the chemical composition of the biofilm was determined using X
      ray diffraction and Fourier transform infrared (FTIR) spectroscopy. The tooth
      specimens in group 2 were incubated with E. faecalis for a period of 6 weeks and
      the topography and ultrastructure of the biofilm were examined using scanning
      electron microscopy (SEM), light microscopy, and laser confocal scanning
      microscopy. The sediments formed from the bacterial interaction on the dentine
      (in group 1) were also examined by SEM and FTIR. These experiments highlighted
      different stages in the interaction of E. faecalis with root canal dentine.
      Further, a bacterial-induced apatite reprecipitation on mature biofilm was also
      observed. This ability of E. faecalis to form such calcified biofilm on root
      canal dentine may be a factor that contributes to their persistence after
      endodontic treatment.

PMID- 16444683
TI  - Influence of plaque biofilm removal on reestablishment of the biocompatibility of
      contaminated titanium surfaces.
AB  - The aim of the present study was to evaluate the influence of plaque biofilm
      removal on the mitochondrial activity of human SaOs-2 osteoblasts grown on
      titanium surfaces. Volunteers wore acrylic splints with structured titanium discs
      for 72 h to build up plaque biofilms (n = 30). Specimens were randomly
      instrumented using either (1) an ultrasonic system at two power settings (EMS1,
      EMS2) + chlorhexidine (CHX), or (2) plastic curettes + CHX. Untreated (NC, n =
      10) and sterile (C, n = 10) titanium discs served as controls. Specimens were
      incubated with SaOs-2 cells for 6 days. Treatment time (T), residual plaque
      biofilm (RPB)/clean implant surface areas (%), mitochondrial cell activity (MA)
      (counts/second), and cell morphology (SEM) were assessed. Statistical analysis
      revealed the following mean scores (+/-SD): RPB areas: P (58.5 +/- 4.9) > EMS1
      (38.4 +/- 4.1) > EMS2 (28.3 +/- 2.0); T: PC (292 +/- 30) = EMS1 (244 +/- 24) >
      EMS2 (199 +/- 25); MA: C (1.544.661 +/- 203.442) > PC (597.559 +/- 566.984) =
      EMS2 (389.875 +/- 409.300) = EMS1 (356.653 +/- 293.863; n.s.) > NC (138.676 +/-
      86.666). In NC and PC groups, cells were predominantly rounded in shape. However,
      in the EMS groups, some cells had started to spread, showing complete
      cytoplasmatic extensions of the cell body on the titanium surface. A monolayer of
      flattened cells was generally observed in the C group. Within the limits of the
      present study, it was concluded that MA seemed to be impaired by the presence of
      RPB areas. However, its removal alone might not be the crucial step in the
      reestablishment of the biocompatibility of titanium surfaces.

PMID- 16444684
TI  - Poly(D,L-lactic acid) coated 45S5 Bioglass-based scaffolds: processing and
      characterization.
AB  - A comparative investigation has been carried out on the mechanical properties and
      bioactivity of Bioglass-based foams, before and after applying a poly(D,L-lactic
      acid) (PDLLA) coating layer on the foam struts. It was found that the bioactivity
      of foams upon immersion in simulated body fluid (SBF) was maintained in the PDLLA
      coated foams; however, the transformation kinetics in SBF of the crystalline
      phase (Na(2)Ca(2)Si(3)O(9)) in the foam struts to an amorphous calcium phosphate
      phase was retarded by PDLLA coating. The compressive and three-point bending
      strengths of the Bioglass-based foams were slightly improved by the PDLLA
      coating, and the work-of-fracture of the foams was considerably enhanced, as
      indicated by stress-strain curves. Immersion in SBF for 4 weeks led to a large
      decrease of the mechanical strength of as-sintered foams decreased (from 0.3 to
      0.03 MPa), because of the transformation of the crystalline phase to an amorphous
      calcium phosphate. On the other hand, the mechanical strength was well-maintained
      in PDLLA-coated foams after immersion in SBF for 8 weeks. This behavior was
      attributed to the in-situ formation of a nanocomposite PDLLA/calcium phosphate
      film on the strut surfaces upon immersion in SBF.

PMID- 16444685
TI  - Tandem electrospray mass spectrometric studies of proton and sodium ion adducts
      of neutral peptides with modified N- and C-termini: synthetic model peptides and
      microheterogeneous peptaibol antibiotics.
AB  - The fragmentations of [M+H]+ and [M+Na]+ adducts of neutral peptides with blocked
      N- and C-termini have been investigated using electrospray ion trap mass
      spectrometry. The N-termini of these synthetically designed peptides are blocked
      with a tertiarybutyloxycarbonyl (Boc) group, and the C-termini are esterified.
      These peptides do not possess side chains that are capable of complexation and
      hence the backbone amide units are the sole sites of protonation and metallation.
      The cleavage patterns of the protonated peptides are strikingly different from
      those of sodium ion adducts. While the loss of the N-terminal blocking group
      occurs quite readily in the case of MS/MS of [M+Na]+, the cleavage of the C
      terminal methoxy group seems to be a facile process in the case of MS/MS of
      [M+H]+ * Fragmentation of the protonated adducts yields only bn ions, while yn
      and a(n) ions are predominantly formed from the fragmentation of sodium ion
      adducts. The a(n) ions arising from the fragmentation of [M+Na](+) lack the N
      terminal Boc group (and are here termed a(n)* ions). MS/MS of [M+Na]+ species
      also yields b(n) ions of substantially lower intensities that lack the N-terminal
      Boc group (b(n)*). A similar distinction between the fragmentation patterns of
      proton and sodium ion adducts is observed in the case of peptides possessing an N
      terminal acetyl group. An example of the fragmentation of the H+ and Na+ adducts
      of a naturally occurring peptaibol from a Trichoderma species confirms that
      fragmentation of these two ionized species yields complementary information,
      useful in sequencing natural peptides. Inspection of the isotopic pattern of b(n)
      ions derived from [M+H]+ adducts of peptaibols provided insights into the
      sequences of microheterogeneous samples. This study reveals that the combined use
      of protonated and sodium ion adducts should prove useful in de novo sequencing of
      peptides, particularly of naturally occurring neutral peptides with modified N-
      and C-termini, for example, peptaibols.

PMID- 16444686
TI  - Feasibility of static secondary ion mass spectrometry to study physicochemical
      interactions between organic components and silver in thermographic systems.
AB  - Chemical engineering of high-technology products requires elucidation of
      intermolecular interactions in complex materials. As part of an extensive study
      on thermographic systems, static secondary ion mass spectrometry (S-SIMS) was
      used to probe the physicochemical behaviour of active compounds, such as
      different tone modifiers and stabilisers, on silver. In particular, the
      feasibility of detecting adsorption and/or binding of individual additives and
      mixtures to silver was examined. Substrates prepared by sputter coating silver on
      silicon wafers were exposed to solutions of the studied compounds in 2-butanone.
      The signal intensities measured with S-SIMS for the ad-layers showed
      reproducibility to within 10%. Radical ions containing silver such as [M-H+Ag]+ *
      were used as evidence for the formation of bonds in the solid. Also the [M
      H+2Ag]+ ions could be assigned to chemisorbed species while [M+Ag]+ ions could be
      formed by adduct ionisation of molecules with co-ejected Ag+ ions. The signal
      intensities of [M-H+Ag]+ * and [M-H+2Ag]+ ions were used to monitor the
      adsorption quantitatively as a function of time.

PMID- 16444687
TI  - Citric acid traps to replace sulphuric acid in the ammonia diffusion of dilute
      water samples for 15N analysis.
AB  - The analysis of 15N in aqueous samples requires the concentration of dissolved
      nitrogen (N) into a small volume that can be analysed by mass spectrometry. This
      is conveniently achieved by the NH3 diffusion technique, where NH4+ is captured
      on small acidified filters enclosed in PTFE. NO3- can be analysed the same way by
      reducing it to NH4+ with Devarda's alloy. H2SO4 is commonly used for the
      acidification of the filters. During combustion, however, this acid leads to the
      production of SO2 and elemental sulphur, which both have detrimental effects on
      the mass spectrometer. We propose here to replace H2SO4 with citric acid because
      it is combusted completely to CO2 and H2O in the elemental analyser before
      entering the mass spectrometer. Citric acid was found to give comparable results
      in terms of N recovery and 15N values, both for NH4+ and for NO3- samples. Blank
      samples revealed that N contamination was slightly lower using citric instead of
      sulphuric acid as acidifier of the glass filters. NH4+ samples first concentrated
      over cation-exchange columns were strongly acidic and several methods were tested
      to raise the pH for the subsequent diffusion. These samples gave incomplete N
      recoveries, but this problem was independent of the acid used on the filters and
      of the final pH of the sample. Complete recovery was achieved only by increasing
      the volume of the eluate from the columns. Citric acid can thus generally be
      recommended instead of H2SO4 for ammonia diffusion.

PMID- 16444688
TI  - Short-term changes in carbon isotope composition of soluble carbohydrates and
      starch: from canopy leaves to the root system.
AB  - Changes in the 13C discrimination of current leaf photosynthesis might have
      profound impacts on root respiratory substrates. Therefore, the aim of this study
      was (1) to refine a method for the isolation of root and leaf starch and soluble
      sugars (neutral fraction) for stable carbon isotope analysis and (2) to assess
      the short-term temporal variability of the C isotope composition (delta13C) of
      starch and of the neutral fraction of beech roots and leaves at different canopy
      heights. An existing method for isolating starch for stable C isotope analysis
      based on enzymatic hydrolysis was modified to account for the low starch content
      of the samples. This was achieved by removing the enzyme (alpha-amylase) by
      ultrafiltration after the hydrolysis, resulting in very low carbon blanks. The
      neutral fraction was separated from organic acids and cations by ion-exchange
      chromatography. An anion-exchange resin in the [HCO3]--form was chosen that
      ensured high precision of C blanks. Beech leaves at 5, 10 and 20 m above the
      forest floor as well as roots were sampled six times during a day/night cycle in
      July 2003. Delta13C values of bulk material, starch and the neutral fraction
      increased from the lower to the higher canopy with mean differences between 5 and
      20 m of 3.8, 3.4 and 2.7 per thousand for the delta13C values of starch, neutral
      fraction and bulk foliage, respectively. The delta13C value of foliar starch
      increased from the morning to the afternoon and decreased during the night, but
      diurnal differences (up to 3.1 per thousand) were only statistically significant
      for leaves sampled at 5 and 10 m height. In roots, no diurnal variation in the
      delta13C of starch was observed during the short time frame of one day and the
      delta13C of the neutral fraction did not differ between samples taken at 16:30
      and 22:00. Calculated delta13C values of starch, which was mobilised during the
      night, were more positive than the total starch (all sampling times pooled) in
      leaves. Furthermore, the delta13C values of mobilised starch were approximately 5
      per thousand more positive than that of the mobilised neutral fraction. Hence,
      the delta13C of potential sources for export from canopy leaves to roots varied
      considerably in their C isotope composition.

PMID- 16444691
TI  - SCAI leaders see exciting future for interventional cardiology.

PMID- 16444689
TI  - Regulation of calcium homeostasis by S100RVP, an androgen-regulated S100 protein
      in the rat ventral prostate.
AB  - BACKGROUND: S100RVP was previously identified as an androgen-response gene in the
      rat ventral prostate (RVP). Characterization of S100RVP is important for
      elucidating the function of S100 proteins in androgen action. METHODS: The
      expression and subcellular localization of S100RVP were determined by Northern
      blot, in situ hybridization, and fluorescent microscopy. Calcium overlay and
      calcium ionophore sensitivity assays were performed to investigate the calcium
      binding and function of S100RVP. RESULTS: S100RVP is abundantly expressed in the
      RVP epithelial cells. A green fluorescent protein(GFP)-S100RVP fusion protein is
      present in both the cytoplasm and nucleus of transfected cells. A GST-S100RVP
      fusion protein bound calcium in vitro at levels similar to known S100 proteins.
      Furthermore, GFP-S100RVP transfected LNCaP and PC3 cells exhibited reduced
      sensitivity to calcium ionophore-induced cell death, but not to UV-induced cell
      death. CONCLUSION: The results of this study argue for a role of S100RVP in
      calcium homeostasis in the prostate.

PMID- 16444692
TI  - Complications of laser dermatologic surgery.
AB  - BACKGROUND AND OBJECTIVE: Innovations in lasers, light and radiofrequency devices
      have allowed for improved therapeutic efficacy and safety and the ability to
      treat patients with an ever-increasing number of medical and aesthetic
      indications. Safety remains a primary concern and the timely communication of
      complications and their management is vital to insure that treatments be as safe
      as possible. The purpose of this report on the Proceedings of the First
      International Laser Surgery Morbidity Meeting is to provide laser experts the
      opportunity to present and discuss complications that their patients have
      experienced and how they were successfully managed. METHODS: Laser experts were
      invited to present complications of laser, light, and radiofrequency treatments
      that their patients have experienced and to discuss the potential mechanisms
      leading to the complications their management and final outcomes. RESULTS:
      Nineteen unique cases are presented and the clinical management of each case
      discussed. Eighteen sets of pre- and post-operative photos are presented.
      CONCLUSION: This report shows that even experts, with extensive experience using
      light-based therapies, can and do have patients who develop complications. Sound
      clinical judgment, and knowing how to avoid complications and their timely post
      operative management, is essential to insure optimal therapeutic outcome.

PMID- 16444693
TI  - The effects of pulse dye laser double-pass treatment intervals on depth of vessel
      coagulation.
AB  - BACKGROUND AND OBJECTIVE: Multi-pass treatments with pulse dye lasers (PDLs) are
      avoided due to perceived side effects. Proper multi-pass techniques allow for
      deeper vascular injury. New extended PDLs allow use of multi-pass procedures.
      This study evaluates how the time between pulses, inter-pulse interval [IPI]
      affect extent of vascular treatment. STUDY DESIGN/MATERIALS AND METHODS: Sixteen
      subjects were exposed to a series of exposures on normal skin to determine depth
      of injury for various IPI. Subjects were exposed to single pass, and 4 double
      pass intervals. Tests included exposures at 0.5 milliseconds, 2-7 j/cm(2).
      Exposures included one and two passes, IPI of 1, 10, 30, and 60 seconds; 5 and 30
      minutes. Treatments were done with PhotoGenica V-Star (595-nm), SmartCool air
      cooling. Biopsies were taken: single pass and double pass purpuric thresholds;
      and at 7 j/cm(2) to determine depth of vascular coagulation. RESULTS: Histology
      revealed increased vascular coagulation depth at purpura threshold for intervals
      of 1, 10, 30, and 60 seconds between passes compared to single pass treatment,
      and a significant monotonic increase in depth of vascular injury at 7 j/cm(2)
      with increasing IPI. CONCLUSIONS: The use of multiple passes increases depth of
      vascular injury, which may increase the efficacy of treatment without significant
      increase in purpura or risk of scarring for treatments at purpura threshold. At
      purpura threshold, the depth of vascular injury increases with increasing IPI up
      to 60 seconds. Above purpura threshold, there is a monotonic increase in depth of
      vascular injury for IPI up to 30 minutes. These observations suggest multi-pass
      treatment methods may be beneficial when employed with PDLs.

PMID- 16444694
TI  - The role of laser fluence in cell viability, proliferation, and membrane
      integrity of wounded human skin fibroblasts following helium-neon laser
      irradiation.
AB  - BACKGROUND: In medicine, lasers have been used predominantly for applications,
      which are broadly termed low level laser therapy (LLLT), phototherapy or
      photobiomodulation. This study aimed to establish cellular responses to Helium
      Neon (632.8 nm) laser irradiation using different laser fluences (0.5, 2.5, 5,
      10, and 16 J/cm(2)) with a single exposure on 2 consecutive days on normal and
      wounded human skin fibroblasts. MATERIALS AND METHODS: Changes in normal and
      wounded fibroblast cell morphology were evaluated by light microscopy. Changes
      following laser irradiation were evaluated by assessing the mitochondrial
      activity using adenosine triphosphate (ATP) luminescence, cell proliferation
      using neutral red and an alkaline phosphatase (ALP) activity assay, membrane
      integrity using lactate dehydrogenase (LDH), and percentage cytotoxicity and DNA
      damage using the Comet assay. RESULTS: Morphologically, wounded cells exposed to
      5 J/cm(2) migrate rapidly across the wound margin indicating a stimulatory or
      positive influence of phototherapy. A dose of 5 J/cm(2) has a stimulatory
      influence on wounded fibroblasts with an increase in cell proliferation and cell
      viability without adversely increasing the amount of cellular and molecular
      damage. Higher doses (10 and 16 J/cm(2)) were characterized by a decrease in cell
      viability and cell proliferation with a significant amount of damage to the cell
      membrane and DNA. CONCLUSIONS: Results show that 5 J/cm(2) stimulates
      mitochondrial activity, which leads to normalization of cell function and
      ultimately stimulates cell proliferation and migration of wounded fibroblasts to
      accelerate wound closure. Laser irradiation can modify cellular processes in a
      dose or fluence (J/cm(2)) dependent manner.

PMID- 16444695
TI  - Bactericidal effects of diode laser on Streptococcus mutans after irradiation
      through different thickness of dentin.
AB  - BACKGROUND AND OBJECTIVES: A reliable method to eradicate the bacteria of
      residual carious dentin has not yet been developed. The aim of this study was to
      evaluate the antibacterial effect of a diode laser on Streptococcus mutans
      through different thickness (500, 1,000, and 2,000 microm) of human dentin. The
      thermal effect of laser irradiation was also investigated. STUDY DESIGN/MATERIALS
      AND METHODS: Dentin specimens were inoculated with 2 microl of S. mutans on one
      side and irradiated by a diode laser on the other side with a power output
      ranging from 0.5 to 7 W. The laser tip was swept with the whole irradiation area
      of 7 mm x 3 mm at a speed of about 10 mm/second with a total irradiation time of
      30 seconds. Cooling with distilled water (30 ml/minute) was applied
      simultaneously during laser irradiation. After laser irradiation, the bacteria
      was removed from the dentin surfaces and cultured for 48 hours at 37 degrees C
      anaerobically to assess the colony forming units (CFU) per ml. The morphology of
      the lased bacteria and the temperature rise during laser irradiation were
      observed by scanning electron microscope (SEM) and measured by thermocouple,
      respectively. RESULTS: The results revealed that 7 W of laser power could kill
      97.7% of CFU through 500 microm thickness of dentin. However, the bactericidal
      efficiency was significantly reduced as the dentin thickness was increased. The
      morphological changes of lased bacteria ranged from less affected such as loss of
      their wall bands and existence of minicells to more severely degenerated, such as
      disintegration and fusion of cells with pores on the cell wall. Only the dentin
      specimens with a thickness of 500 microm exhibited a temperature rise greater
      than 5.5 degrees C after receiving 5 or 7 W of laser irradiation. CONCLUSIONS: A
      diode laser can eliminate the Streptococcus mutans of the residual carious dentin
      without inducing high pulpal temperature rise when the remaining dentin thickness
      is greater than 1 mm.

PMID- 16444696
TI  - Laser resection technique and results of multiple lung metastasectomies using a
      new 1,318 nm Nd:YAG laser system.
AB  - BACKGROUND AND OBJECTIVES: Advantages of a new 1,318 nm Nd:YAG laser based on
      multiple lung metastasectomies are shown. STUDY DESIGN/MATERIALS AND METHODS:
      Ninety-three percent of 328 patients with metastases (8/patient, range 1-124) had
      precision laser resections (lobectomy-rate reduced to 7%); this laser delivers 20
      kW/cm(2) 1,318 nm power densities with 400 microm fibers, and a focussing
      handpiece. Absorption in water is tenfold higher. RESULTS AND CONCLUSIONS:
      Between 1/1996 and 12/2003 in 328 patients (164 males/females, 61 years) 3,267
      nodules were removed. Pathologic examination revealed 2,546 metastases (range 3
      80 mm) from kidney (n = 112), colorectal (n = 91), and breast cancers (n = 35).
      In 85% of patients where the complete resection was achieved the 5-year survival
      was 41%. For remaining 15% (incomplete resection) the 5-year survival was 7%.
      Five-year survival for patients with 10 (and more) metastases was 28%, for
      patients with 20 (and more) was 26%. No 30-day mortality was observed.
      CONCLUSION: This new laser system facilitates any kind of parenchymal lung
      resection in lobe-sparing manner and in case of complete resection improves
      significantly the survival.

PMID- 16444697
TI  - Transcranial application of low-energy laser irradiation improves neurological
      deficits in rats following acute stroke.
AB  - BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) has been shown to have
      beneficial effects on ischemic skeletal and heart muscles tissues. The aim of the
      present study was to approve the effectiveness of LLLT treatment at different
      locations on the brain in acute stroked rats. STUDY DESIGN/MATERIALS AND METHODS:
      Stroke was induced in 169 rats that were divided into four groups: control non
      laser and three laser-treated groups where laser was employed ipsilateral,
      contralateral, and both to the side of the induced stroke. Rats were tested for
      neurological function. RESULTS: In all three laser-treated groups, a marked and
      significant improvement in neurological deficits was evident at 14, 21, and 28
      days post stroke relative to the non-treated group. CONCLUSIONS: These
      observations suggest that LLLT applied at different locations in the skull and in
      a rather delayed-phase post stroke effectively improves neurological function
      after acute stroke in rats.

PMID- 16444699
TI  - Theoretical study on structures and stabilities of [H,Ge,C,N].
AB  - Theoretical investigations are performed for the first time on the simplest
      hydrogenated germanium cyanide [H,Ge,C,N], whose analogs [H,C(2),N] and
      [H,Si,C,N] have been detected in space and laboratory, respectively. The detailed
      potential energy surfaces in both singlet and triplet states are constructed at
      the CCSD(T)/6-311+G(3df,2p)//B3LYP/6-31G(d)+ZPVE level, including 18 minimum
      isomers and 26 interconversion transition states. The former three low-lying and
      kinetically stabilized isomers are HGeCN (1)1 (0.0 kcal/mol), HGeNC (1)2 (5.1
      kcal/mol), and cyclic cCHNGe(1)7 (11.1 kcal/mol). In addition, five isomers HCNGe
      (1)3 (33.8), HNCGe (1)5 (29.8), cNHCGe (1)8 (37.9), HGeCN (3)1 (30.1), and HNCGe
      (3)5 (26.5) each have considerable barriers, despite their high energies. Future
      laboratory characterization and astrophysical detection of the eight [H,Ge,C,N]
      isomers, especially the former three low-lying species (1)1, (1)2, and (1)7, are
      highly recommended. The accurate spectroscopic data at the QCISD/6-311G(d,p)
      level are provided. For some species, the CBS-QB3 calculations are also
      performed. Wherever possible, comparisons with the analogous [H,C(2),N] and
      [H,Si,C,N] are made on the structural, energetic, and bonding properties.

PMID- 16444700
TI  - On the suitability of strictly localized orbitals for hybrid QM/MM calculations.
AB  - In the QM/MM method we have developed (LSCF/MM), the QM and the MM parts are held
      together by means of strictly localized bonding orbitals (SLBOs). Generally these
      SLBOs are derived from localized bond orbitals (LBOs) that undergo tails
      deletion, resulting in a nonpredictable change of their properties. An
      alternative set of SLBOs is provided by the extremely localized molecular
      orbitals (ELMOs) approach, where the orbitals are rigorously localized on some
      prefixed atoms without tails on the other atoms of the molecule. A comparative
      study of SLBOs arising from various localization schemes and ELMOs is presented
      to test the reliability and the transferability of these functions within the
      Local Self-Consistent Field (LSCF) framework. Two types of chemical bonds were
      considered: C--C and C--O single bonds. The localized functions are obtained on
      the ethane and the methanol molecules, and are tested on beta-alanine and diethyl
      ether molecules. Moreover, the various protonation forms of beta-alanine have
      been investigated to illustrate how well the polarity variation of the chemical
      bond can be handled throughout a chemical process. At last, rotation energy
      profiles around C--C and C--O bonds are reproduced for butane and fluoromethanol.
      Energetic, geometric, as well as electronic factors all indicate that ELMO
      functions are much more transferable from one molecule to another, leading to
      results closer to the usual SCF reference than any other calculations involving
      any other localized orbitals. When the shape of the orbital is the most important
      factor then ELMO functions will perform as well as any other localized orbital.

PMID- 16444701
TI  - Newt orthologue of Growth arrest-specific 6 (NvGas6) is implicated in stress
      response during newt forelimb regeneration.
AB  - Red-spotted newts are capable of regenerating various structures and organs
      through the process of epimorphic regeneration. Receptor tyrosine kinases (RTKs)
      and their ligands are important for normal cellular development and physiology
      but most have not yet been characterised during regeneration. We have isolated a
      newt orthologue of Growth arrest-specific 6 (NvGas6), and examined its expression
      during forelimb regeneration and within a blastema cell line (B1H1). During limb
      regeneration, NvGas6 expression increases upon amputation, peaks during maximal
      blastema cell proliferation, and is subsequently downregulated during
      redifferentiation. Transcripts are localised to the wound epithelium and distal
      mesenchymal cells during dedifferentiation and proliferative phases, and
      scattered within redifferentiating tissues during later stages. In B1H1 cultures,
      NvGas6 is upregulated under reduced serum conditions and myogenesis. Treatment
      with mimosine and colchicine or exposure to heat shock or anoxia results in
      upregulation of NvGas6 expression. Taken together, our findings suggest that
      during regeneration, NvGas6 expression may be upregulated in response to cellular
      stress.

PMID- 16444702
TI  - Hybrid density functional theory for pi-stacking interactions: application to
      benzenes, pyridines, and DNA bases.
AB  - The suitability of a hybrid density functional to qualitatively reproduce
      geometric and energetic details of parallel pi-stacked aromatic complexes is
      presented. The hybrid functional includes an ad hoc mixture of half the exact
      (HF) exchange with half of the uniform electron gas exchange, plus Lee, Yang, and
      Parr's expression for correlation energy. This functional, in combination with
      polarized, diffuse basis sets, gives a binding energy for the parallel-displaced
      benzene dimer in good agreement with the best available high-level calculations
      reported in the literature, and qualitatively reproduces the local MP2 potential
      energy surface of the parallel-displaced benzene dimer. This method was further
      critically compared to high-level calculations recently reported in the
      literature for a range of pi-stacked complexes, including monosubstituted benzene
      benzene dimers, along with DNA and RNA bases, and generally agrees with MP2
      and/or CCSD(T) results to within +/-2 kJ mol(-1). We also show that the resulting
      BH&H binding energy is closely related to the electron density in the
      intermolecular region. The net result is that the BH&H functional, presumably due
      to fortuitous cancellation of errors, provides a pragmatic, computationally
      efficient quantum mechanical tool for the study of large pi-stacked systems such
      as DNA.

PMID- 16444703
TI  - Methylation of RAS association domain family protein 1A as a biomarker of lung
      cancer.
AB  - BACKGROUND: Promoter hypermethylation is an important mechanism for silencing
      tumor-suppressor genes in cancer and a promising tool for development of
      molecular biomarkers. This study aimed to determine the prevalence of RAS
      association domain family protein 1A (RASSF1A) promoter hypermethylation in
      bronchial aspirates of patients with suspected lung cancer and to test whether
      this type of methylation assay could be used as a diagnostic adjunct to
      conventional cytology. METHODS: Two hundred three bronchial aspirates from
      patients with suspected lung cancer were analyzed for RASSF1A hypermethylation by
      using a sensitive quantitative methylation-specific polymerase chain reaction
      (QMSP). RESULTS: RASSF1A hypermethylation was found in 88% (35 of 40), 28% (31 of
      111), and 100% (6 of 6) of bronchial aspirates collected from patients diagnosed
      with small cell lung cancer, nonsmall cell lung cancer, and combined small cell
      lung cancer, respectively. No hypermethylation was detected in patients diagnosed
      with nonneoplastic lung disease (0 of 46). Depending on histologic subtype, up to
      82% of cases presenting with a negative histology showed a positive methylation
      assay. CONCLUSIONS: The QMSP analysis of RASSF1A hypermethylation enabled a
      highly specific distinction between patients diagnosed with lung cancer and those
      with nonneoplastic lung disease. These results suggested that a QMSP assay is a
      promising molecular tool for diagnosis of primary lung cancer.

PMID- 16444704
TI  - Numerical distribution of lymphoid nodules in the human sigmoid colon,
      rectosigmoidal junction, rectum, and anal canal.
AB  - There is little information on the numerical distribution of lymphoid nodules
      (LN) in distal segments of the human large bowel. A novel approach was therefore
      developed to assess the number of LN in the sigmoid colon, the rectosigmoid
      segment, the rectum, and the anal canal in humans. The distal large bowel from
      five cadavers was selected for quantitative study. The number of LN was scored
      macroscopically from the proximal sigmoid colon to the distal anal canal. A
      numerical distribution, previously unreported, consisting of two circular bands
      of LN was observed in each of the five cadavers. One band was located 3 cm
      proximal from the pectinate line and the other was located at the rectosigmoid
      segment. Significantly more LN occurred 3-5 cm proximal to the pectinate line
      compared to areas distal or proximal to this band of LN. This band of LN has not
      been reported previously in humans.

PMID- 16444706
TI  - The irreversible decline in anatomical confidence amongst surgical trainees: fact
      or fiction.

PMID- 16444707
TI  - Predicting the redox state and secondary structure of cysteine residues in
      proteins using NMR chemical shifts.
AB  - We report 2D cluster analyses of 1Halpha, 1HN, 13Calpha, and 13C' versus 13Cbeta
      NMR chemical shifts (CSs) that can be used to predict the redox state and
      secondary structure of cysteine residues in proteins. A database of cysteine
      1Halpha, 1Hbeta2, 1Hbeta3, 1HN, 13Calpha, 13Cbeta, 13C', and 15NH CSs as a
      function of secondary structure and redox state was constructed from
      BioMagResBank entries. One-dimensional statistical analysis showed that cysteine
      1Halpha, 1HN, 13Calpha, 13C', and 15NH CSs reflected the secondary structure, and
      that cysteine Cbeta CS is extremely sensitive to the redox state. In contrast,
      cysteine 1Hbeta CS was not correlated with its redox state or secondary
      structure. Two-dimensional cluster analysis revealed that 2D Calpha/Cbeta,
      C'/Cbeta, HNu/Cbeta, and Halpha/Cbeta clusters were helpful in distinguishing
      both the redox state and secondary structure of cysteine residues. Based on these
      results, we derived rules using a score matrix to predict the redox state and
      secondary structure of cysteines using their CSs. The score matrix predicts the
      redox state and secondary structure of cysteine residues in proteins with
      approximately 90% accuracy. This suggests that the redox state and secondary
      structure of cysteine residues in peptides and proteins can be obtained from
      their CSs without recourse to nuclear Overhauser effect measurements.

PMID- 16444709
TI  - Microvascular and epithelial permeability measurements in laboratory animals.
AB  - Disruption of the mucosal permeability barrier is an acute life-threatening
      consequence of intestinal transplantation. The major aim of organ preservation
      techniques is to maintain the mucosal barrier and its function. Thus, assessment
      of microvascular and epithelial permeability is an important tool to determine
      the efficacy of therapeutic interventions. The use of murine models is
      particularly advantageous, as numerous immunological approaches (e.g., monoclonal
      antibodies) and genetically modified animal strains have been developed. Large
      animal models are also useful because they allow online detection of mucosal
      permeability changes. In this review, we summarize the available methodologies
      for measuring microvascular and epithelial permeability in the intestines of
      laboratory animals. We describe the advantages of various photometric and
      intravital microscopic methods for the assessment of microvascular permeability.
      Techniques that determine the inward and outward direction of mucosal
      permeability changes (including radioenzymatic, fluorimetric, and intravital
      microscopy methods) are also discussed.

PMID- 16444710
TI  - Is there a role for microsurgery in the prevention of arm lymphedema secondary to
      breast cancer treatment?
AB  - The secondary lymphedema of the upper limb (post-mastectomy lymphedema) has an
      incidence, in patients who underwent axillary lymphadenectomy for breast cancer,
      between 5 to 25%, up to 40% after radiotherapic treatment. We studied 50 patients
      treated for breast cancer. The patients were divided in two groups of 25 each,
      comparable for age, sex, pathology and treatment and followed up to 5 years after
      operation for breast. One group of 25 patients was controlled only clinically
      (physical examination, water volumetry) at 1-3-6 months and 1-3-5 years from
      breast cancer treatment. The other group of 25 patients was followed also by
      lymphatic scintigraphy performed pre-operatively and after 1-3-6 months and 1-3-5
      years from operation. In the first group, followed only clinically, lymphedema
      appeared in 9 patients after a period variable from 1 week to 2 years, with
      highest incidence between 3 and 6 months. In the second group of 25 patients, the
      preventive therapeutic protocol allowed to have a clinically evident arm
      lymphedema only in 2 patients. The comparison of the two groups of 25 patients
      proved a statistically significant difference in the appearance of arm secondary
      lymphedema (p = 0.01, using Fisher's exact test). The diagnostic and therapeutic
      preventive procedures allow to reduce the incidence rate of lymphedema
      significantly, in comparison with patients who did not undergo this protocol of
      prevention.

PMID- 16444711
TI  - Learning microsurgical suturing and knotting techniques: comparative data.
AB  - Correctly performed surgical sutures are the basis of surgical safety. This
      retrospective survey was conducted among participants (n = 263) taking graduate
      and postgraduate courses between 2000-2004. Placement of sutures, time to perform
      knotting, safety of knots, and quality of knot stability were tested. None of the
      students had been previously instructed in microsurgical techniques. At the
      beginning of the training program, 90-95% of participants damaged the suturing
      thread at several places. By the end of the course, knotting times significantly
      decreased in both groups. Graduates decreased their time from 6.8 +/- 2.34 min to
      3.28 +/- 0.71 min (mean +/- standard error of the mean), and postgraduates
      decreased their time from 5.02 +/- 3.25 min to 1.54 +/- 0.54 min (mean +/-
      standard error of the mean). In our opinion, "mass training" to teach the basics
      of microsurgery is not a good approach. Instead, individual training should be
      provided, as tutors offer invaluable advice, and adjust almost each stitch and
      knot during teaching sessions.

PMID- 16444713
TI  - Regulatory dendritic cells modulate immune responses via induction of T-cell
      apoptotic death.
AB  - We describe a regulatory lymphoid dendritic cell (LDC) population propagated from
      mouse liver nonparenchymal cells (NPC) in IL-3 and anti-CD40 monoclonal antibody
      that are phenotypically mature, and induce T-cell hyporesponsiveness by promoting
      T-cell apoptotic death, which is partially caspase-dependent, but is unlikely to
      be mediated by soluble factor(s). In vivo administration of liver LDC
      significantly prolonged the survival of vascularized cardiac allografts in an
      alloantigen-specific manner. This is associated with enhanced T-cell death in
      secondary lymphoid organs.

PMID- 16444712
TI  - Tbx1 is regulated by forkhead proteins in the secondary heart field.
AB  - Transcriptional regulation in a tissue-specific and quantitative manner is
      essential for developmental events, including those involved in cardiovascular
      morphogenesis. Tbx1 is a T-box-containing transcription factor that is
      responsible for many of the defects observed in 22q11 deletion syndrome in
      humans. Tbx1 is expressed in the secondary heart field (SHF) and is essential for
      cardiac outflow tract (OFT) development. We previously reported that Tbx1 is
      regulated by sonic hedgehog by means of forkhead (Fox) transcription factors in
      the head mesenchyme and pharyngeal endoderm, but how it is regulated in the SHF
      is unknown. Here, we show that Tbx1 expression in the SHF is regulated by Fox
      proteins through a combination of two evolutionarily conserved Fox binding sites
      in a dose-dependent manner. Cell fate analysis using the Tbx1 enhancer suggests
      that SHF-derived Tbx1-expressing cells contribute extensively to the right
      ventricular myocardium as well as the OFT during early development and ultimately
      give rise to the right ventricular infundibulum, pulmonary trunk, and pulmonary
      valves. These results suggest that Fox proteins are involved in most, if not all,
      Tbx1 expression domains and that Tbx1 marks a subset of SHF-derived cells,
      particularly those that uniquely contribute to the right-sided outflow tract and
      proximal pulmonary artery.

PMID- 16444714
TI  - Distribution of peripheral blood cells in mice after splenectomy or
      autotransplantation.
AB  - Our aim was to compare the distribution changes of peripheral leukocytes and
      erythrocytes in splenectomized and spleen-autotransplanted BALB/c female mice (n
      = 96), 2 and 8 months after surgery. In total, there were eight groups of
      animals: splenectomy, autotransplantation, sham, and untreated controls at both
      time points. We used the spleen-apron method of Furka et al. (Khirurgiia (Mosk)
      1989;9:125-127), inserting five spleen chips into the greater omentum, for
      autotransplantation. Quantitative and qualitative blood cell counts and the
      phagocytic activity of cells (stimulated with zymosan) were determined. In
      splenectomized animals, the number of neutrophils significantly increased 8
      months after surgery. The greatest phagocytic activity of neutrophils, however,
      was observed in autotransplanted animals of the same age. In splenectomized
      animals, erythrocyte volumes were significantly higher in the second
      postoperative month, but normalized by the eighth month. In conclusion, spleen
      autotransplantation has some beneficial effects, including clearing erythrocytes
      and preserving the phagocytic activity of neutrophils in peripheral blood.

PMID- 16444715
TI  - Allogeneic acute rejection on fetal small-bowel graft: role of gangliosides.
AB  - In previous work, it was shown that gangliosides (Gang) have an inhibitory effect
      on lymphocyte proliferation as well as on delayed-type hypersensitivity response
      and mixed lymphocyte reaction. Therefore, we decided to examine the effect of
      gangliosides in acute allorejection after fetal intestinal transplantation. We
      used two female C57BL/6 mice on pregnancy day 19 as a source of fetal intestine.
      All animals were anesthetized with ketamine (70 mg/kg) and xylazine (10 mg/kg),
      intramuscularly. We harvested intestinal segments of 1 cm to transplant into
      BALB/c and C57BL/6 mice (male, weighing around 20 g) used as recipients. They
      were divided into groups of six animals each: isogeneic and allogeneic without
      treatment, or treated with tacrolimus 1 mg/kg/day, or gangliosides 3 and 9
      mg/kg/day, during 7 days posttransplantation, intramuscularly. On postoperative
      day 7, intestinal grafts were collected and fixed in 10% formalin solution. Using
      an anesthetic overdose as euthanasia, we removed the intestinal grafts. Tissue
      samples were stained with hematoxylin-eosin for histological analysis regarding
      grafts development (D) and rejection (R) aspects. Data were analyzed by the
      Kruskal-Wallis test, considering P < or = 0.05 as significant. In the isogeneic
      and tacrolimus groups, we observed a very good degree of development (D = 9 +/-
      0.5; D = 9 +/- 0.4, respectively), but a severe degree of rejection (R = 15 +/-
      1.3) and a low degree of development (D = 1 +/- 0.8) in animals without
      treatment. The ganglioside groups showed D = 5 +/- 1.6 and R = 13 +/- 3.3, and D
      = 7 +/- 2.9 and R = 9 +/- 1.9, for the 3-mg and 9-mg groups, respectively. There
      was a statistically significant difference between the ganglioside groups and
      allogeneic groups without treatment. Based on the above data, we conclude that
      avascular fetal intestine transplantation is a good experimental model for
      studying immunological events, and that gangliosides only partially modulate the
      allorejection response, allowing intestinal development, mainly at the highest
      ganglioside dose. Maybe immunomodulation would be better observed by using
      isolated types of gangliosides or association with other immunosuppressive drugs.

PMID- 16444716
TI  - Esophagus reconstruction with free jejunal transfer.
AB  - Following pharyngolaryngectomy, reconstruction is one of the most challenging
      surgical procedures. Here we review our own experiences using a microvascularly
      transferred free jejunal graft. This method was performed in 22 patients (19 male
      and 3 female, aged 40-63 years). Seven patients underwent neoadjuvant chemo
      radiotherapy. Eighteen patients had immediate reconstruction after
      pharyngolaryngectomy, and 4 patients had delayed reconstruction because of
      complications from previous surgeries (2 stenoses, and 2 recurrent cancers). The
      duration of surgery ranged from 5-9 h (mean, 6.3 h), and the ischemic time of the
      graft was 70-125 min (mean, 88 min). This method has several advantages: it is a
      one-step operation; the graft is covered by self-cleaning mucosa; the development
      of fistulas and stenoses is rare; and the technique provides good swallowing.
      Owing to its good blood supply, this reconstructive method can also be used in
      previously irradiated areas.

PMID- 16444718
TI  - Training protocol for feline renal transplantation, using rat vascular
      anastomosis.
AB  - Renal transplantation (RTx) has been a potential treatment for renal failure in
      pet cats. We developed a training protocol for the microsurgical skills required
      for feline RTx using rat vessels, which are the same size as the feline renal
      artery and vein. Using interrupted sutures, the transected abdominal aorta was
      reestablished in an end-to-end fashion. Venous anastomosis was performed with a
      continuous running suture in an end-to-side fashion between the portal vein and
      inferior vena cava. In the arterial anastomotic model, technical errors were
      checked by postoperative hemorrhaging. Those failures in the venous anastomotic
      model, technical errors were confirmed by the rat's death. Histological
      examinations of the epithelialization at the anastomotic site were evaluated in
      both groups. After training, nine cases of feline RTx were performed safely,
      using an adequate microsurgical technique.

PMID- 16444719
TI  - Immune regulatory activity of liver-derived dendritic cells generated in vivo.
AB  - Hepatic tolerance is demonstrated by spontaneous acceptance of liver allografts
      in mice. Hepatic dendritic cells (DC) play a crucial role in determining immunity
      or tolerance. In this study, we adopted an approach to transfect gene(s) into the
      mouse liver by tail-vein injection of plasmid-carrying genes. Transfection with
      GM-CSF expanded liver CD11c+ myeloid DC (LMDC), while liver B220+CD11c- lymphoid
      DC (LLDC) were expanded after transfection of IL-3 and CD40L. Flow analysis
      revealed that these liver DC subsets were phenotypically mature following
      overnight culture. However, in contrast to LMDC, LLDC induced hyporesponsiveness
      in allogeneic T-cells, with suppressed secretion of both IL-2 and IFN-gamma, and
      prolonged cardiac allograft survival. This immune regulatory DC population in the
      liver may play a role in modulating T-cell immunity in the liver.

PMID- 16444720
TI  - Heme oxygenase 1 expression in postischemic reperfusion liver damage: effect of L
      arginine.
AB  - Ischemia/reperfusion (I/R) injury is a multifactorial process that affects liver
      function after transplantation and resectional surgery. Alterations in hepatic
      microcirculation and decreased hepatic flow can cause local hypoxia and
      consequently liver damage, which is worsened by reperfusion. The aim of this
      study was to evaluate if treatment with L-arginine improved hepatic function in
      rats with I/R injury. Animals were treated with L-arginine, ischemized for 30
      min, and reperfused for 3 h. Plasmatic levels of GOT, GPT, lipid hydroperoxides
      (LOOH), and total thiol groups (RSH) were evaluated. In addition, we analyzed
      hepatic LOOH and RSH levels, DNA fragmentation, heme oxygenase 1 (HO-1)
      expression, and histological modifications. Our results demonstrate a significant
      improvement in hepatic function of I/R rats compared to the control group.
      Treatment with L-arginine increased the expression of HO-1. These data suggest
      that L-arginine could be useful in preventing oxidative damage during hepatic
      surgery.

PMID- 16444721
TI  - Hemorheological follow-up after splenectomy and spleen autotransplantation in
      mice.
AB  - We previously reported on a spleen autotransplantation model in mice, with spleen
      function studies at 6 weeks. The present study was undertaken to investigate long
      term hemorheological functions. A/J and BALB/c inbred mice were divided into four
      groups: control, sham surgery (SH), splenectomy (SE), and spleen
      autotransplantation (AU). Hematological and hemorheological parameters were
      determined. Leukocyte counts in the SE and AU groups were significantly higher
      than in controls, while hematocrit levels were markedly lower. Mean erythrocyte
      volume did not change significantly. Platelet counts in the AU group were
      significantly lower, and red blood cell deformability was significantly worse in
      the SE group. The AU group also had increased cell transit time, but it was less
      than that in the SE group. The SE group showed the highest fibrinogen levels. We
      conclude that there are some consistent differences in hematological parameters
      between splenectomy and spleen autotransplantation. These data suggest that
      spleen autotransplantation may partially restore hemorheological functions
      following splenectomy.

PMID- 16444722
TI  - Brief communication: unusual finding at Pueblo Bonito: multiple cases of
      hyperostosis frontalis interna.
AB  - Hyperostosis frontalis interna (HFI) is a disease characterized by excess bone
      growth on the internal lamina of the frontal bone and, occasionally, other
      cranial bones. Although the disease is fairly common in modern populations, its
      etiology is poorly understood. Hyperostosis frontalis interna has been identified
      in antiquity, primarily in the Old World, but with a much lower frequency than in
      modern groups. The purpose of the present study is to report multiple cases of
      HFI at Pueblo Bonito (Chaco Canyon, New Mexico). Twelve out of 37 adults with
      observable frontal bones exhibited HFI, ranging from mild to severe, including 11
      females and one male. This is the first published case report of HFI in
      archaeological remains from the New World having a frequency comparable with
      modern groups. Most archaeological cases of HFI are isolated, so comparative data
      for multiple cases at one site are rare. The results of this study emphasize the
      importance of looking for HFI in archaeological remains, although it is rarely
      observed. Possible genetic and environmental factors for the high frequency of
      HFI at Chaco Canyon are considered, but additional research is needed to discover
      the etiology and to better understand why HFI sometimes occurs at modern
      frequencies in ancient populations.

PMID- 16444723
TI  - Intestinal ischemic preconditioning in rats and NF-kappaB activation.
AB  - Cold preservation prior to small-bowel transplantation can moderate tissue
      injury, although it is unable to protect the bowel graft from acute reperfusion
      injury. One method to reduce oxidative stress is ischemic preconditioning (IPC).
      The limited data regarding IPC of the bowel encouraged us to investigate the key
      factor in this process, i.e., the activation of nuclear factor-kappa binding (NF
      kB) in bowel tissue. The intestine was preconditioned by various cycles of IPC on
      rats. Activation of NF-kB was detected by a chemiluminescence-based ELISA method.
      Our findings showed that NF-kB level was elevated significantly 30 min after IPC.
      One hour following IPC, NF-kB decreased to control level; 2 h after IPC, the
      level significantly increased again. These changes were independent of the number
      of IPC cycles. Our experiments with various IPC cycles revealed that even a very
      short IPC cycle was able to activate the IPC cascade in small-bowel tissue.

PMID- 16444724
TI  - Murine fetal small-intestine grafts: morphometric and immunohistochemical
      evaluation.
AB  - We investigated histopathological changes following murine fetal intestinal
      transplantation. Fetal intestine, obtained from a pregnant C57BL/6 mouse, was
      transplanted into BALB/c and C57Bl/6 mice. Recipients were divided into three
      groups: isogeneic, and allogeneic treated with 3 mg/kg/day gangliosides (Allo-a)
      or 9 mg/kg/day (Allo-b). One week after transplant, all grafts showed good
      viability, confirmed by cellular mitosis in the mucosa and a well-defined propria
      muscular layer. Isogeneic grafts showed a thicker muscular layer than in the Allo
      a (P = 0.02) and Allo-b (P = 0.004) groups. There was no difference in number of
      mitotic cells among groups. Goblet cells were significantly reduced in allografts
      treated with 3 mg gangliosides (P = 0.013) or 9 mg gangliosides (P = 0.002)
      compared to isografts. Villi height was similar in all studied groups. There was
      no difference in positivity of the enteric nervous system among groups. Atrophy
      was more common in the allogeneic groups, suggesting that isografts had better
      development than allografts treated with gangliosides. (

PMID- 16444725
TI  - Use of nonpenetrating vascular closure staples in feline renal transplantation.
AB  - Renal transplantation is a potential treatment for irreversible renal failure in
      pet cats. Our aim is to reduce warm ischemic time by using nonpenetrating
      vascular closure staples (VCS), thereby improving graft survival. Experimental
      cats were divided into the VCS group (n = 4; autotransplantation) or suture group
      (n = 6; allotransplantation). The renal artery was anastomosed with the external
      iliac artery in an end-to-end fashion, and the renal vein was attached to the
      external iliac vein in an end-to-side fashion. Warm ischemic time as well as
      arterial and venous anastomotic times were measured. Cats in the suture group
      were administrated cyclosporine and prednisolone orally after transplantation.
      Ischemic and anastomotic times in the VCS group were significantly reduced
      compared with the suture group. Two of 6 allografts had a ureteral anastomotic
      stricture, and 4 allografts were rejected. Histological findings of autografts
      showed normal structure. In conclusion, VCS staples were useful in feline renal
      transplantation.

PMID- 16444726
TI  - Measurement of erythrocyte deformability and methodological adaptation for small
      animal microsurgical models.
AB  - Measuring erythrocyte deformability with bulk filtrometers is common, but there
      are problems with standardization and sample quantity in small laboratory
      animals. In this study, blood was drawn from mice, rats, and dogs, and then
      erythrocyte suspensions at 1-5% hematocrit were prepared. Bulk filtrometers with
      a 5- or 3-microm pore-diameter filter were used to determine the initial relative
      filtration rate (IRFR) and relative cell transit time (RCTT). Hematological
      composition was also tested. In all species, the highest IRFR values occurred at
      1% hematocrit, and the lowest values at 5%. In mice and rats, RCTT values were
      lowest at 1% and highest at 5% using a 5-microm filter, whereas in dogs, RCTT was
      elevated at 1-2%. Using a 3-microm filter, each species showed the same phenomena
      under 3%. RCTT values may become distorted above a certain cell-size/pore-size
      ratio. In mice and rats, 1% suspension is applicable for bulk filtrometry, but
      only using 5-microm filters.

PMID- 16444727
TI  - Paleodemography of a medieval population in Japan: analysis of human skeletal
      remains from the Yuigahama-minami site.
AB  - The purpose of this study is to obtain demographic data regarding the medieval
      population buried at the Yuigahama-minami site in Kamakura, Japan, and to detect
      a secular trend in the life expectancy of Japanese population over the last
      several thousand years. The Yuigahama-minami skeletal sample consists of 260
      individuals, including 98 subadults (under 20 years old) and 162 adults. A
      Yuigahama-minami abridged life-table analysis yielded a life expectancy at birth
      (e0) of 24.0 years for both sexes, a life expectancy at age 15 years (e15) of
      15.8 years for males, and an e15 of 18.0 years for females. The reliability of
      the estimated e0 was confirmed by analysis of the juvenility index. Demographic
      profiles comparing the Yuigahama-minami series with other skeletal series
      indicated that both the survivorship curve and life expectancy of the Yuigahama
      minami sample are similar to those of the Mesolithic-Neolithic Jomon population,
      but are far lower than those of the early modern Edo population. These
      comparisons strongly suggest that life expectancy changed little over the
      thousands of years between the Mesolithic-Neolithic Jomon and medieval periods,
      but then improved remarkably during the few hundred years between the medieval
      period and early modern Edo period. The short-lived tendency of the Yuigahama
      minami sample does not contradict the archaeological hypothesis of unsanitary
      living conditions in medieval Kamakura. This is the first investigation to
      address the demographic features of a medieval population in Japan, and will help
      refine our understanding of long-term trends in the demographic profiles of
      inhabitants of Japan.

PMID- 16444728
TI  - Early African Diaspora in colonial Campeche, Mexico: strontium isotopic evidence.
AB  - Construction activities around Campeche's central park led to the discovery of an
      early colonial church and an associated burial ground, in use from the mid-16th
      century AD to the late 17th century. Remains of some individuals revealed dental
      mutilations characteristic of West Africa. Analyses of strontium isotopes of
      dental enamel from these individuals yielded unusually high (87)Sr/(86)Sr ratios,
      inconsistent with an origin in Mesoamerica, but consistent with an origin in West
      Africa in terrain underlain by the West Africa Craton, perhaps near the port of
      Elmina, a principal source of slaves for the New World during the 16th century.
      These individuals likely represent some of the earliest representatives of the
      African Diaspora in the Americas.

PMID- 16444729
TI  - Influence of cranial deformation on facial morphology among prehistoric South
      Central Andean populations.
AB  - Calculating biodistances among South American populations using cranial
      measurements is often hindered, as many available skeletal collections exhibit
      deformation. Acknowledging vault modifications, researchers have sought
      measurements in other regions which are unaffected by deformation. In the 1970s,
      a set of 10 "relatively" unaffected facial measurements was identified in
      Argentinean crania that later became the basis of numerous South American
      biodistance studies. These measurements include: minimum frontal breadth,
      bizygomatic breadth, orbit height, orbit breadth, palate breath, palate length,
      upper facial height, basion-prosthion length, nasal height, and nasal breadth.
      Palate length was excluded from the present analysis due to considerable
      measurement error. The suitability of these measurements in populations other
      than Argentineans has not been rigorously tested. Using a sample of 350
      prehistoric crania from the Museo Arqueologico San Miguel de Azapa (MASMA, Arica,
      Chile), this project tested the hypothesis that these measurements are unaffected
      by either annular or tabular deformation. Results obtained from MANOVA analysis
      indicate this hypothesis cannot be fully supported. Among males, only 3 of the 9
      measurements are unaffected by either form of deformation (palate breadth, basion
      prosthion length, and nasal breadth), while analysis of females indicates that 4
      of the 9 measurements remain unaltered (minimum frontal breadth, orbit breadth,
      basion-prosthion length, and nasal breadth). Additionally, analogous to the
      vault, facial measurements display patterns consistent with the deformation
      applied. Two implications can be drawn from this research: 1) previous studies
      using these measurements must be interpreted cautiously, and 2) researchers using
      these measurements must explicitly test their suitability in each population.

PMID- 16444730
TI  - Dominance and reproductive rates in captive female olive baboons, Papio anubis.
AB  - The reproductive cycles of 23 captive olive baboons were studied over two
      successive parturitions. Interbirth intervals of 450 days were reduced by 60% in
      comparison to wild baboons, and consisted of 145 days of postpartum amenorrhea,
      3.5 cycles, and a gestation of 185 days. Dominance rank was found to be one
      significant factor affecting female fertility. Low-ranking females had longer
      total intervals between successive births and, in particular, they experienced a
      longer delay to conception once they had resumed sexual cycles. Mothers of
      infants who were heavy for age resumed cycling more quickly and had fewer cycles
      before a subsequent conception. Mothers best able to sustain rapid early infant
      growth were those of high dominance rank and of high body mass; these females had
      more rapid reproductive rates. As female energy intake was unrelated to
      dominance, we suggest that social stresses are important suppressors of the
      hormonal and lactational competence of subordinate females.

PMID- 16444732
TI  - New strepsirrhine primate from the late Eocene of Peninsular Thailand (Krabi
      Basin).
AB  - In this paper, we describe the newly discovered lower jaw of a primate from the
      late Eocene Krabi coal mine (Bang Mark pit) of Peninsular Thailand. We performed
      microtomographic examinations at the European Synchrotron Radiation Facility
      (ESRF, Grenoble, France) to analyze different morphological aspects of the jaw
      and teeth. Although partially preserved, this fossil mandible reveals a set of
      distinctive dental traits (e.g., double-rooted P(2) and molarized P(4)) that
      allow us to describe a new stepsirrhine adapiform: Muangthanhinius siami, new
      genus and species. This taxon is somewhat atypical among Paleogene adapiforms,
      and more specialized than the sivaladapid adapiforms (hoanghoniines) that existed
      in Asia in the same epoch. In fact, Muangthanhinius shows a degree of dental
      specialization approximating that of some modern strepsirrhine lemuriforms,
      although it lacks the highly specialized anterior dentition characterizing this
      living primate group (canine + incisors forming a very procumbent toothcomb). In
      contrast, Muangthanhinius exhibits a large canine deeply anchored within the
      dentary that probably protruded high above the toothrow. Finally, despite the
      development of a molarized P(4) as in Miocene sivaladapid sivaladapines,
      Muangthanhinius differs in molar morphology from this group, and the position of
      this new taxon within the Adapiformes remains indeterminate. Clarification of its
      phylogenetic position will require more morphological evidence than is currently
      available.

PMID- 16444733
TI  - Intestinal parasite infections and fecal steroid levels in wild chimpanzees.
AB  - Immune-endocrine interactions have been evaluated much less frequently in
      nonhuman primates, and this may be due, in part, to logistical and ethical
      concerns regarding trapping and sampling of endangered species, especially apes.
      Using noninvasive fecal collection methods, the present study evaluates possible
      relationships between fecal steroid levels and gastrointestinal parasite
      infections in the Ngogo chimpanzee community in Kibale National Park, Uganda.
      Because both testosterone and cortisol exhibit immunosuppressive effects in vitro
      and in other animal models, it was hypothesized that both testosterone and
      cortisol would be positively associated with gastrointestinal parasite infections
      in these animals. When placed in a mixed model simultaneously, both testosterone
      (F = 4.98, df = 1, P = 0.033) and cortisol (F = 5.94, df = 1, P = 0.020) were
      positively associated with total (helminth and protozoan) parasite richness (the
      number of unique intestinal parasite species recovered from hosts' fecal
      samples). It is possible that androgens and corticoids alter the ability of a
      host to mount an effective immune response against concomitant infection with
      multiple parasitic species. The utility of fecal samples for assessing immune
      endocrine interactions is discussed.

PMID- 16444734
TI  - Intercusp relationships of the permanent maxillary first and second molars in
      American whites.
AB  - Much of a human molar's morphology is concentrated on its occlusal surface. In
      view of embryologists' recent attention on the determination of crown morphology
      by enamel knots that initiate cusp formation, we were interested in the
      arrangement of cusp apices in the definitive tooth. Computer-assisted image
      analysis was used to measure intercusp distances and angles on permanent
      maxillary M1 and M2 in a sample of 160 contemporary North American whites. The
      intent was to generate normative data and to compare the size and variability
      gradients from M1 to M2. There is little sexual dimorphism in intercusp distances
      or angles, even though the conventional mesiodistal (MD) and buccolingual (BL)
      crown size is 2.0% and 4.0% larger in males, respectively, in these same teeth.
      Dimensions decreased in size and increased in variability from M1 to M2, but
      differentially. Cusps of the trigon were more stable between teeth, especially
      the paracone-protocone relationship. Principal components analysis on the six M1
      distances disclosed only one eigenvalue above 1.0, indicating that overall crown
      size itself is the paramount controlling factor in this tooth that almost
      invariably exhibits a hypocone. In contrast, four components were extracted from
      among the 12 angular cusp relationships in M1. These axes of variation may prove
      useful in studies of intergroup differences. A shape difference occurs in M2,
      depending on whether the hypocone is present; when absent, the metacone is moved
      lingually, creating more of an isosceles arrangement for the cusps of the trigon.
      Statistically, correlations are low between occlusal intercusp relationships and
      conventional crown diameters measured at the margins of the crowns that form
      later. Weak statistical dependence between cusp relationships and traditional MD
      and BL diameters suggest that separate stage- and location-specific molecular
      signals control these different parts (and different stages) of crown formation.

PMID- 16444735
TI  - Comparative analysis of mRNA and protein expression of Popdc1 (Bves) during early
      development in the chick embryo.
AB  - The isolation of the Popeye gene family was based on its preferential expression
      in striated muscle tissue. Recently, a monoclonal antibody against chick Popdc1
      (also known as Bves) became available and was used in this study to comparatively
      analyze the expression pattern of Popdc1 at both the protein and mRNA level
      during early chick embryogenesis. Using whole-mount immunohistochemistry,
      expression in the heart was first observed at Hamburger and Hamilton (HH) stage
      10 in the presumptive left ventricular segment. Cardiac expression was confined
      to differentiated cardiac myocytes, and undifferentiated myocytes at the anterior
      and posterior pole showed little expression. After looping, the outer curvature
      myocardium showed prominent Popdc1 staining, whereas the inner curvature was
      unlabeled. Despite previous reports, Popdc1 protein was not detectable at any
      time point in the proepicardium, epicardium, or the smooth muscle layer of the
      coronary vessels. Whole-mount in situ hybridization using a full-length Popdc1
      probe detected novel expression domains, which have not been described
      previously. Popdc1 mRNA was found in Hensen's node at HH stage 4, and by HH stage
      5+, expression became asymmetric. In addition, Popdc1 mRNA was found in
      pharyngeal endoderm and in the notochordal plate. Subsequently, beginning at HH
      stage 9, Popdc1 mRNA expression was found in the cardiac mesoderm and expression
      was maintained in the heart in a pattern very similar to the one observed by
      antibody staining.

PMID- 16444736
TI  - Experimental hypoxia and embryonic angiogenesis.
AB  - We examined the role of hypoxia and HIF factors in embryonic angiogenesis and
      correlated the degree of hypoxia with the level of HIF and VEGF expression and
      blood vessel formation. Quail eggs were incubated in normoxic and hypoxic (16%
      O(2)) conditions. Tissue hypoxia marker, pimonidazol hydrochloride, was applied
      in vivo for 1 hr and detected in sections with Hypoxyprobe-1 Ab. VEGF and HIF
      expression was detected by in situ hybridization. HIF-1alpha protein was detected
      in sections and by Western blot. Endothelial cells were visualized with QH-1
      antibody. Hypoxic regions were detected even in normoxic control embryos, mainly
      in brain, neural tube, branchial arches, limb primordia, and mesonephros. The
      expression patterns of HIF-1alpha and HIF-1beta factors followed, in general, the
      Hypoxyprobe-1 marked regions. HIF-2alpha was predominantly expressed in
      endothelial cells. Diffuse VEGF expression was detected in hypoxic areas of
      neural tube, myocardium, digestive tube, and most prominently in mesonephros.
      Growing capillaries were directed to areas of VEGF positivity. Hypoxic regions in
      hypoxic embryos were larger and stained more intensely. VEGF and HIF-1 factors
      were proportionately elevated in Hypoxyprobe-1 marked regions without being
      expressed at new sites and were followed by increased angiogenesis. Our results
      demonstrate that normal embryonic vascular development involves the HIF-VEGF
      regulatory cascade. Experimentally increasing the level of hypoxia to a moderate
      level resulted in over-expression of HIF-1 factors and VEGF followed by an
      increase in the density of developing vessels. These data indicate that embryonic
      angiogenesis is responsive to environmental oxygen tension and, therefore, is not
      entirely genetically controlled.

PMID- 16444737
TI  - Covalently immobilized enzyme gradients within three-dimensional porous
      scaffolds.
AB  - Horseradish peroxide (HRP) was covalently coupled to three-dimensional (3D) silk
      fibroin scaffolds using water-soluble carbodiimide. Stable, bilaterally
      symmetrical immobilized HRP gradient patterns were generated within 3D silk
      fibroin scaffolds using the principles of diffusion. Gradients of immobilized HRP
      activity were controlled using variables of volume and concentration of HRP
      solution activated by the carbodiimide. The method developed can be extended to
      immobilize a variety of proteins and small molecules on several types of porous,
      interconnected materials. This technique of patterning enzymes and proteins in a
      gradient manner offers new options in the field of chemotaxis, tissue
      engineering, and biosensors.

PMID- 16444738
TI  - Intrinsic disorder is a key characteristic in partners that bind 14-3-3 proteins.
AB  - Proteins named 14-3-3 can bind more than 200 different proteins, mostly (but not
      exclusively) when they are at a phosphorylated state. These partner proteins are
      involved in different cellular processes, such as cell signaling, transcription
      factors, cellular morphology, and metabolism; this suggests pleiotropic
      functionality for 14-3-3 proteins. Recent efforts to establish a rational
      classification of 14-3-3 binding partners showed neither structural nor
      functional relatedness in this group of proteins. Using three natural predictors
      of disorder in proteins, and the structural available information, we show that
      >90% of 14-3-3 protein partners contain disordered regions. This percentage is
      significantly high when compared with recent studies on cell signaling and cancer
      related proteins or RNA chaperons. More important, almost all 14-3-3-binding
      sites are inside disordered regions, this reinforcing the importance of
      structural disorder in this class of proteins. We also propose that a disorder-to
      order transition occurs in the binding of 14-3-3 proteins with their partners. We
      discuss the consequences of the latter for consensus binding sequences,
      specificity, affinity, and thermodynamic control.

PMID- 16444739
TI  - On the influence of oxygen and cell concentration in an SFPR whole cell
      biocatalytic Baeyer-Villiger oxidation process.
AB  - Efficient whole cell biotransformations, in particular microbial whole cell
      Baeyer-Villiger oxidation with molecular oxygen, demand comprehension and
      optimization of the process details involved. Optimal provision of oxygen and
      control of bioprocess parameters are pivotal for their success. The interrelation
      of cell density and oxygen supply in an in situ substrate feeding and product
      removal (SFPR) whole cell Baeyer-Villiger oxidation process was investigated in
      detail. Both parameters were optimized with respect to practical considerations.
      The outcome of this study supports a schematic process model, allows estimation
      of optimum process conditions and exploration of its limits.

PMID- 16444740
TI  - Two types of transmembrane homomeric interactions in the integrin receptor family
      are evolutionarily conserved.
AB  - Integrins are heterodimers, but recent in vitro and in vivo experiments suggest
      that they are also able to associate through their transmembrane domains to form
      homomeric interactions. Two fundamental questions are the biological relevance of
      these aggregates and their form of interaction in the membrane domain. Although
      in vitro experiments have shown the involvement of a GxxxG-like motif, several
      crosslinking in vivo data are consistent with an almost opposite form of
      interaction between the transmembrane alpha-helices. In the present work, we have
      explored these two questions using molecular dynamics simulations for all
      available integrin types. We have tested the hypothesis that homomeric
      interactions are evolutionary conserved, and essential for the cell, using
      conservative substitutions to filter out nonnative interactions. Our results show
      that two models, one involving a GxxxG-like motif (model I) and an almost
      opposite form of interaction (model II) are conserved across all alpha and beta
      integrin types, both in homodimers and homotrimers, with different specificities.
      No conserved interaction was found for homotetramers. Our results are completely
      independent from experimental data, both during molecular dynamics simulations
      and in the selection of the correct models. We rationalize previous seemingly
      conflicting findings regarding the nature of integrin interhelical homomeric
      interactions.

PMID- 16444741
TI  - Protein instability during HIC: describing the effects of mobile phase conditions
      on instability and chromatographic retention.
AB  - Hydrophobic interaction chromatography (HIC) is known to be potentially
      denaturing to proteins, but the effects of mobile phase conditions on
      chromatographic behavior are not well understood. In this study, we apply a model
      describing the effects of secondary protein unfolding equilibrium on
      chromatographic behavior, including the effects of salt concentration on both
      stability and adsorption. We use alpha-lactalbumin as a model protein that in the
      presence and absence of calcium, allows evaluation of adsorption parameters for
      folded and unfolded species independently. The HIC adsorption equilibrium under
      linear binding conditions and solution phase protein stability have been obtained
      from a combination of literature and new experiments. The effect of salt
      concentration on protein stability and the rate constant for unfolding on the
      chromatographic surface have been determined by fitting the model to isocratic
      chromatography data under marginally stable conditions. The model successfully
      describes the effects of added calcium and ammonium sulfate. The results
      demonstrate the importance of considering the effects on stability of mobile
      phase modifiers when applying HIC to marginally stable

PMID- 16444742
TI  - Laser-scanning lithography (LSL) for the soft lithographic patterning of cell
      adhesive self-assembled monolayers.
AB  - We report the development of laser-scanning lithography (LSL), which employs a
      laser-scanning confocal microscope to pattern photoresists that can be utilized,
      for example, in the fabrication of masters for use in soft lithography. This
      convenient technique provides even exposure across the entire view field and
      facilitates accurate alignment of successive photoresist exposures. Features on
      the scale of 3 microm have been achieved to date with a 10x objective (NA 0.45).
      Virtual masks, instructions for laser irradiation, were drawn using the Region of
      Interest (ROI) function of a Zeiss LSM 510 microscope. These regions were then
      exposed to a 458 nm argon laser for 32 micros (0.9 mW/microm(2)). Differential
      interference contrast (DIC) imaging was utilized with a non-destructive 514 nm
      argon laser as an immediate quality check of each exposure, to align successive
      exposures, and to reduce chromatic aberration between imaging and exposure.
      Developed masters were replica-molded with poly(dimethylsiloxane) (PDMS); these
      masters were then utilized for microcontact printing of cell-adhesive self
      assembled monolayers (SAMs) to demonstrate the utility of this process. Initial
      studies confirmed that human dermal fibroblast adhesion and spreading were
      limited to cell-adhesive SAM areas. LSL is a rapid, flexible, and readily
      available technique that will accelerate master design and preparation; moreover,
      it can be applied to additional forms of photolithography and photopolymerization
      for studies in cell biology, biomaterials design and evaluation, materials
      science, and surface chemistry.

PMID- 16444743
TI  - Probabilistic reporting of EUS-FNA cytology: Toward improved communication and
      better clinical decisions.
AB  - BACKGROUND: The objectives of this study were to determine threshold
      probabilities needed to perform endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) and those needed to treat patients suspected of having
      malignancy and then to compare these thresholds to the pre- and posttest
      probabilities of malignancy associated with benign, atypical, suspicious, and
      malignant diagnoses. The goal was to aid endoscopists in making appropriate
      clinical decisions based on both quantitative and qualitative approaches.
      METHODS: The study included 633 consecutive patients. A decision tree was
      constructed to estimate the "treatment" threshold. Using treatment threshold and
      likelihood ratios, the authors determined the "no-test-test" and "test-treatment"
      thresholds. Pretest probability was compared with no-test-test and test-treatment
      thresholds, and the post-EUS-FNA probability of malignancy for each diagnostic
      category with the treatment threshold. Results were stratified by lesion site,
      lesion size, and cytopathologist. RESULTS: EUS-FNA has a wide range of pretest
      probabilities within which it could be performed (0.06-0.98). The posttest
      probabilities for malignancy, 0.99 (95% confidence interval [CI], 0.967-0.996)
      and 0.09 (95% CI, 0.057-0.126), after a positive or a negative result,
      respectively, were significantly different from the treatment threshold but not
      those of suspicious, 0.92 (95% CI, 0.767-0.994) diagnosis. The posttest
      probability of atypical diagnosis, 0.60 (95% CI, 0.407-0.772), was not
      significantly different from that of pretest probability. Results did not vary by
      lesion size, organ site, or cytopathologist. CONCLUSION: The authors demonstrated
      the uncertainty associated with EUS-FNA diagnostic categories and used the
      threshold approach to qualify quantitatively the decision to perform EUS-FNA and
      the decision to treat patients suspected of having malignancy.

PMID- 16444744
TI  - Inhibition of human telomerase reverse transcriptase by nonsteroidal
      antiinflammatory drugs in colon carcinoma.
AB  - BACKGROUND: Telomerase activation, which is observed in most human cancers, plays
      an important role in carcinogenesis. Human telomerase reverse transcriptase
      (hTERT) is a subunit of telomerase that is essential for telomerase activity. The
      aim of the study was to investigate whether nonsteroidal antiinflammatory drugs
      (NSAIDs) inhibit telomerase activity and hTERT. METHODS: Four colon carcinoma
      cell lines, HT-29, COLO205, CRL-2134, and SW1116, were used in the experiments.
      Polymerase chain reaction-based telomeric repeat amplification (TRAP) enzyme
      linked immunosorbent assay (ELISA) was used to measure telomerase activity in the
      cells after treatment with aspirin, indomethacin, or SC-236 (a specific
      cyclooxygenase-2 [COX-2] inhibitor). Expression of hTERT mRNA and protein was
      detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western
      blotting, respectively. The dual luciferase reporter assay was performed to
      identify the potential cis-response elements to NSAIDs in the promoter region of
      hTERT. RESULTS: Aspirin, indomethacin, and SC-236 inhibited telomerase activity
      in HT-29, COLO205, and CRL-2134 cell lines, but not in the SW1116 cell line.
      NSAIDs inhibited hTERT mRNA and protein expression through suppression of hTERT
      transcriptional activity. The hTERT promoter fragment -145 to -330 basepairs (bp)
      upstream of the ATG starting site was sufficient to respond to the NSAID-induced
      inhibitory effect and the inhibition was COX-2-independent. CONCLUSION: NSAIDs
      inhibit telomerase activity at hTERT transcriptional, mRNA, and protein levels in
      colon carcinoma cells. The hTERT promoter fragment -145 to -330 bp may be the cis
      response element to NSAIDs.

PMID- 16444745
TI  - His239Arg SNP of HRAD9 is associated with lung adenocarcinoma.
AB  - BACKGROUND: It was previously reported that a functional human (h) Rad9 protein
      accumulated in the nuclei of non-small cell lung carcinoma (NSCLC) cells. Those
      experiments, however, did not examine whether the hRad9 gene was mutated in those
      cells. The sequence of the HRAD9 gene in NSCLC cells was investigated. METHODS:
      The sequence of the HRAD9 was examined in tumor and peripheral normal lung
      tissues obtained from 50 lung adenocarcinoma patients during surgery. The
      expression of its mRNA using reverse transcription polymerase chain reaction (RT
      PCR) was also examined. RESULTS: No sequence alterations were detected in the
      HRAD9 gene, which was found to be normally transcribed in surgically resected
      lung carcinoma cells. However, in eight (16.0%) cases a single nucleotide
      polymorphism (SNP) was observed at the second position of codon 239 (His/Arg
      heterozygous variant) of the gene. This frequency was significantly higher than
      that found in the normal population. CONCLUSIONS: Whereas the capacity to produce
      a functional hRad9 protein was intact in lung adenocarcinoma cells, a
      nonsynonymous SNP of HRAD9 was detected that might be associated with the
      development of lung adenocarcinoma.

PMID- 16444747
TI  - Disease-free and overall survival after pathologic complete disease remission of
      cytologically proven inflammatory breast carcinoma axillary lymph node metastases
      after primary systemic chemotherapy.
AB  - BACKGROUND: Breast carcinoma axillary lymph node (ALN) pathologic complete
      response (pCR) after primary chemotherapy is associated with significantly higher
      recurrence-free survival (RFS) and overall survival (OS) rates. The purpose of
      the current study was to determine long-term outcome in patients achieving a pCR
      of cytologically proven inflammatory breast carcinoma ALN metastases after
      primary chemotherapy. METHODS: Patients with cytologically documented ALN
      metastases from inflammatory breast carcinoma were treated in three prospective
      primary chemotherapy trials. After surgery, patients were subdivided into those
      patients with and those patients without residual ALN carcinoma. Survival was
      calculated using the Kaplan-Meier method. RESULTS: Of 175 patients treated, 61
      had cytologically confirmed ALN metastases. Fourteen patients (23%) achieved a
      pCR of the ALNs after primary chemotherapy. The 5-year OS and RFS rates were
      found to be improved in those patients achieving a pCR of the ALNs (82.5% [95%
      confidence interval (95% CI), 62.8-100%] and 78.6% [95%CI, 59.8-100%],
      respectively, vs. 37.1% [95%CI, 25.4-54.2%] and 25.4% [95%CI, 15.5-41.5%],
      respectively) (P = 0.01 [for OS] and P = 0.001 [for RFS]). Combination
      anthracycline and taxane-based primary chemotherapy resulted in significantly
      more patients achieving an ALN pCR (45% vs. 16%; P = 0.01). CONCLUSIONS: pCR of
      ALN metastases is associated with an excellent prognosis in patients with
      inflammatory breast carcinoma. The rates of ALN pCR are nearly 50% in patients
      with inflammatory breast carcinoma who are treated with anthracyclines and weekly
      paclitaxel before surgery. However, those patients with residual ALN disease at
      the time of surgery greatly require the introduction of novel therapeutic
      strategies.

PMID- 16444746
TI  - Valproate enhances imatinib-induced growth arrest and apoptosis in chronic
      myeloid leukemia cells.
AB  - BACKGROUND: The objective of this study was to evaluate the ability of the
      clinically available histone deacetylase (HDAC) inhibitor valproate to enhance
      the cytotoxicity of the Bcr-Abl inhibitor imatinib in imatinib-resistant cell
      lines. METHODS: Interactions between imatinib, and valproate have been examined
      in imatinib-sensitive and -resistant chronic myeloid leukemia (CML)cell lines
      (K562, KCL-22, CML-T1) and in bone marrow mononuclear cells (MNCs) derived from
      imatinib-resistant CML patients. RESULTS: In imatinib-sensitive cell lines,
      cotreatment with imatinib 0.5 muM and valproate 5 microM for 48 hours potently
      enhanced imatinib-induced growth arrest and apoptosis. In resistant cell lines
      and in primary MNCs derived from imatinib-rsistant patients, valproate restored
      sensitivity to the cytotoxic effects of imatinib. Coexposure of cells to
      valproate and imatinib was associated with repression of several genes involved
      in Bcr-Abl transformation. In particular, the combination valproate-imatinib
      downregulated the expression of Bcr-Abl and the antiapoptotic protein Bcl-2,
      which is particularly overexpressed in imatinib-resistant clones. CONCLUSIONS:
      Data from this study suggested that administration of the clinically available
      HDAC inhibitor valproate may be a powerful strategy to enhance cytotoxic effects
      of imatinib in those patient resistant to imatinib or in which complete
      cytogenetic remission has been not reached.

PMID- 16444748
TI  - Implications for clinical staging of metastatic cutaneous squamous carcinoma of
      the head and neck based on a multicenter study of treatment outcomes.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the head and neck is a
      common cancer that has the potential to metastasize to lymph nodes in the parotid
      gland and neck. Previous studies have highlighted limitations with the current
      TNM staging system for metastatic skin carcinoma. The aim of this study was to
      test a new staging system that may provide better discrimination between patient
      groups. METHODS: A retrospective multicenter study was conducted on 322 patients
      from three Australian and three North American institutions. All had metastatic
      cutaneous SCC involving the parotid gland and/or neck and all were treated for
      cure with a minimum followup time of 2 years. These patients were restaged using
      a newly proposed system that separated parotid disease (P stage) from neck
      disease (N stage) and included subgroups of P and N stage. Metastases involved
      the parotid in 260 patients (149 P1; 78 P2; 33 P3) and 43 of these had clinical
      neck disease also (22 N1; 21 N2). Neck metastases alone occurred in 62 patients
      (26 N1; 36 N2). Ninety percent of patients were treated surgically and 267 of 322
      received radiotherapy. RESULTS: Neck nodes were pathologically involved in 32% of
      patients with parotid metastases. Disease recurred in 105 (33%) of the 322
      patients, involving the parotid in 42, neck in 33, and distant sites in 30.
      Parotid recurrence did not vary significantly with P stage. Disease-specific
      survival was 74% at 5 years. Survival was significantly worse for patients with
      advanced P stage: 69% survival at 5 years compared with 82% for those with early
      P stage (P = 0.02) and for those with both parotid and neck node involvement
      pathologically: 61% survival compared with 79% for those with parotid disease
      alone (P = 0.027). Both univariate and multivariate analysis confirmed these
      findings. Clinical neck involvement among patients with parotid metastases did
      not significantly worsen survival (P = 0.1). CONCLUSIONS: This study, which
      included a mixed cohort of patients from six different institutions, provides
      further information about the clinical behavior of metastatic cutaneous SCC of
      the head and neck. The hypothesis that separation of parotid and neck disease in
      a new staging system is supported by the results. The benefit of having subgroups
      of P and N stage is uncertain, but it is likely to identify patients with
      unfavorable characteristics that may benefit from further research.

PMID- 16444750
TI  - Interaction between mammalian glyceraldehyde-3-phosphate dehydrogenase and L
      lactate dehydrogenase from heart and muscle.
AB  - The exceptionally high protein concentration in living cells can favor functional
      protein-protein interactions that can be difficult to detect with purified
      proteins. In this study we describe specific interactions between mammalian D
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and L-lactate dehydrogenase
      (LDH) isozymes from heart and muscle. We use poly(ethylene-glycol) (PEG)-induced
      coprecipitation and native agarose electrophoresis as two independent methods
      uniquely suited to mimic some of the conditions that can favor protein-protein
      interaction in living cells. We found that GAPDH interacts with heart or muscle
      isozymes of LDH with approximately one-to-one stoichiometry. The interaction is
      specific; GAPDH shows interaction with two LDH isozymes that have very different
      net charge and solubility in PEG solution, while no interaction is observed with
      GAPDH from other species, other NAD(H) dehydrogenases, or other proteins that
      have very similar net charge and molecular mass. Analytical ultracentrifugation
      showed that the LDH and GAPDH complex is insoluble in PEG solution. The
      interaction is abolished by saturation with NADH, but not by saturation with
      NAD(+) in correlation with GAPDH solubility in PEG solution. The crystal
      structures show that GAPDH and LDH isozymes share complementary size, shape, and
      electric potential surrounding the active sites. The presented results suggest
      that GAPDH and LDH have a functional interaction that can affect NAD(+)/NADH
      metabolism and glycolysis in living cells.

PMID- 16444749
TI  - Molecular classification of mucoepidermoid carcinomas-prognostic significance of
      the MECT1-MAML2 fusion oncogene.
AB  - Mucoepidermoid carcinomas (MECs) of the salivary and bronchial glands are
      characterized by a recurrent t(11;19)(q21;p13) translocation resulting in a MECT1
      MAML2 fusion in which the CREB-binding domain of the CREB coactivator MECT1 (also
      known as CRTC1, TORC1 or WAMTP1) is fused to the transactivation domain of the
      Notch coactivator MAML2. To gain further insights into the molecular pathogenesis
      of MECs, we cytogenetically and molecularly characterized a series of 29 MECs. A
      t(11;19) and/or an MECT1-MAML2 fusion was detected in more than 55% of the
      tumors. Several cases with cryptic rearrangements that resulted in gene fusions
      were detected. In fusion-negative MECs, the most common aberration was a single
      or multiple trisomies. Western blot and immunohistochemical studies demonstrated
      that the MECT1-MAML2 fusion protein was expressed in all MEC-specific cell types.
      In addition, cotransfection experiments showed that the fusion protein
      colocalized with CREB in homogeneously distributed nuclear granules. Analyses of
      potential downstream targets of the fusion revealed differential expression of
      the cAMP/CREB (FLT1 and NR4A2) and Notch (HES1 and HES5) target genes in fusion
      positive and fusion-negative MECs. Moreover, clinical follow-up studies revealed
      that fusion-positive patients had a significantly lower risk of local recurrence,
      metastases, or tumor-related death compared to fusion-negative patients (P =
      0.0012). When considering tumor-related deaths only, the estimated median
      survival for fusion-positive patients was greater than 10 years compared to 1.6
      years for fusion-negative patients. These findings suggest that molecularly
      classifying MECs on the basis of an MECT1-MAML2 fusion is histopathologically and
      clinically relevant and that the fusion is a useful marker in predicting the
      biological behavior of MECs.

PMID- 16444751
TI  - Native-specific stabilization of flavodoxin by the FMN cofactor: structural and
      thermodynamical explanation.
AB  - Flavodoxins are useful models to investigate protein/cofactor interactions. The
      binding energy of the apoflavodoxin-FMN complex is high and therefore the
      holoflavodoxin is expected to be more stable than the apoprotein. This
      expectation has been challenged by reports on the stability of Desulfovibrio
      desulfuricans flavodoxin indicating that FMN binds to the unfolded polypeptide
      with similar affinity as to the native state, thus causing no net effect on
      protein stability. In previous work, we have analyzed in detail the stability of
      the apoflavodoxin from Anabaena PCC 7119 and the energetics of its functional
      complex with FMN. Here, we use the Anabaena holoprotein to directly investigate
      the contribution of the bound cofactor to protein stability through a detailed
      analysis of the chemical and thermal denaturation equilibria. Our data clearly
      shows that FMN binding largely stabilizes the protein towards both chemical and
      thermal denaturation, and that the stabilization observed at 25 degrees C in low
      ionic strength conditions is precisely the one expected if full release of the
      cofactor takes place upon flavodoxin unfolding. On the other hand, the binding of
      FMN to the native polypeptide is shown to simplify the thermal unfolding so that,
      while apoflavodoxin follows a three-state mechanism, the holoprotein unfolds in a
      two-state fashion. Comparison of the X-ray structure of native apoflavodoxin with
      the phi-structure of the thermal intermediate indicates that the increase in
      cooperativity driven by the cofactor originates in its preferential binding to
      the native state, which is a consequence of the disorganization in the
      intermediate of the FMN binding loops and of an adjacent longer loop.

PMID- 16444752
TI  - Enzymatic hydrolysis of polysaccharide-rich particulate organic waste.
AB  - Hydrolysis of organic particulates in rapid fermentative processes can be
      inhibited. The volatile fatty acids (VFA) released during fermentation reduce pH.
      Whether VFA or the drop in pH inhibits hydrolysis is unclear. The effects of pH
      and acetate on the enzymatic hydrolysis of a potato sample that contains both
      carbohydrate and protein were studied at fixed pH (5-9) in the presence/absence
      of 20 g/L of acetate. Experimental results showed that the effects of pH and
      acetate on the hydrolysis of carbohydrate differed from those on the hydrolysis
      of protein. Numerous kinetic models fitted the hydrolysis data obtained during
      the first 40 h of hydrolysis when inhibitory effects were insignificant. The Chen
      Hashimoto model was used herein to fit the hydrolysis data obtained during 144 h
      of reaction. Also, the non-competitive inhibition model of three inhibitors
      (H(+), OH(-), total/undissociated/dissociated acetate) successfully described the
      inhibition of the hydrolysis of both carbohydrate and protein.

PMID- 16444753
TI  - Lymphatic microsurgery for the treatment of lymphedema.
AB  - One of the main problems of microsurgery for lymphedema consists of the
      discrepancy between the excellent technical possibilities and the subsequently
      insufficient reduction of the lymphoedematous tissue fibrosis and sclerosis.
      Appropriate treatment based on pathologic study and surgical outcome have not
      been adequately documented. Over the past 25 years, more than 1000 patients with
      peripheral lymphedema have been treated with microsurgical techniques. Derivative
      lymphatic micro-vascular procedures has today its most exemplary application in
      multiple lymphatic-venous anastomoses (LVA). For those cases where a venous
      disease is associated to more or less latent or manifest lymphostatic pathology
      of such severity to contraindicate a lymphatic-venous shunt, reconstructive
      lymphatic microsurgery techniques have been developed (autologous venous grafts
      or lymphatic-venous-Iymphatic-plasty - LVLA). Objective assessment was undertaken
      by water volumetry and lymphoscintigraphy. Subjective improvement was noted in
      87% of patients. Objectively, volume changes showed a significant improvement in
      83%, with an average reduction of 67% of the excess volume. Of those patients
      followed-up, 85% have been able to discontinue the use of conservative measures,
      with an average follow-up of more than 7 years and average reduction in excess
      volume of 69%. There was a 87% reduction in the incidence of cellulitis after
      microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the
      treatment of peripheral lymphedema and should be the therapy of choice in
      patients who are not sufficiently responsive to nonsurgical treatment. Improved
      results can be expected with operations performed earlier at the very first
      stages of lymphedema.

PMID- 16444754
TI  - Characterization of supersaturated lidocaine/polyacrylate pressure sensitive
      adhesive systems: thermal analysis and FT-IR.
AB  - Supersaturated and crystallized lidocaine (LC)/pressure sensitive adhesive (PSA)
      systems have been studied by differential scanning calorimetry (DSC) and FT-IR
      with the objective of characterizing the thermodynamic states and compatibility
      of the two-component systems. Analysis of the phase behavior of LC/DT2287 systems
      indicates that LC and DT2287 are thermodynamically miscible within the
      composition range containing less than approximately 20% w/w LC, beyond which LC
      may crystallize from the blends forming a separated crystalline phase. The
      composition dependence of the glass transition temperature (T(g)) was used to
      characterize the physical and thermodynamic states of the supersaturated systems.
      The Fox, Gordon-Taylor, Kwei, Kovacs, and Brekner, Schneider and Cantow (BSC)
      equations were employed to conduct the analysis. It was found that the PSA in the
      supersaturated LC/PSA systems underwent significant entropic relaxation upon
      mixing. LC in the miscible systems is absorbed into and swells the polymer
      network of the PSA, thereby exhibiting reduced molecular mobility, while the PSA
      attains significant molecular conformation relaxation and entropy increase. It
      was also found that LC molecules extensively participate in molecular relaxation
      of the PSA throughout the composition range studied. The molecular mobility of LC
      is inhibited as the volume fraction of DT2287 increases, suggesting that the PSA
      molecular network reduces the molecular mobility of LC by closely involving LC
      molecules in its relaxation, and thereby may enhancing the physical stability of
      the systems. No strong intermolecular interactions between the two components
      were found based upon the results of T(g)-composition analysis, and was confirmed
      by FT-IR studies. This indicates that the analysis based on the BSC equation
      provides more precise characterization of polymer systems than the T(g) 
      composition analysis based on other equations cited.

PMID- 16444755
TI  - Pharmaceutical co-crystals.
AB  - Crystal engineering has evolved in such a manner that it is now synonymous with
      the paradigm of supramolecular synthesis, that is, it invokes self-assembly of
      existing molecules to generate a wide range of new solid forms without the need
      to break or form covalent bonds. This review addresses how crystal engineering
      has been applied to active pharmaceutical ingredients, API's, with emphasis upon
      how pharmaceutical co-crystals, a long known but little explored alternative to
      the four traditionally known forms of API, can be generated in a rational
      fashion. Case studies on Carbamazepine (CBZ) and Piracetam are presented which
      illustrate the relative ease with which pharmaceutical co-crystals can be
      prepared and their diversity in terms of composition and physical properties.

PMID- 16444756
TI  - The alpha-to-beta conformational transition of Alzheimer's Abeta-(1-42) peptide
      in aqueous media is reversible: a step by step conformational analysis suggests
      the location of beta conformation seeding.
AB  - Current views of the role of beta-amyloid (Abeta) peptide fibrils range from
      regarding them as the cause of Alzheimer's pathology to having a protective
      function. In the last few years, it has also been suggested that soluble
      oligomers might be the most important toxic species. In all cases, the study of
      the conformational properties of Abeta peptides in soluble form constitutes a
      basic approach to the design of molecules with "antiamyloid" activity. We have
      experimentally investigated the conformational path that can lead the Abeta-(1
      42) peptide from the native state, which is represented by an alpha helix
      embedded in the membrane, to the final state in the amyloid fibrils, which is
      characterized by beta-sheet structures. The conformational steps were monitored
      by using CD and NMR spectroscopy in media of varying polarities. This was
      achieved by changing the composition of water and hexafluoroisopropanol (HFIP).
      In the presence of HFIP, beta conformations can be observed in solutions that
      have very high water content (up to 99 % water; v/v). These can be turned back to
      alpha helices simply by adding the appropriate amount of HFIP. The transition of
      Abeta-(1-42) from alpha to beta conformations occurs when the amount of water is
      higher than 80 % (v/v). The NMR structure solved in HFIP/H2O with high water
      content showed that, on going from very apolar to polar environments, the long N
      terminal helix is essentially retained, whereas the shorter C-terminal helix is
      lost. The complete conformational path was investigated in detail with the aid of
      molecular-dynamics simulations in explicit solvent, which led to the localization
      of residues that might seed beta conformations. The structures obtained might
      help to find regions that are more affected by environmental conditions in vivo.
      This could in turn aid the design of molecules able to inhibit fibril deposition
      or revert oligomerization processes.

PMID- 16444757
TI  - A CD14 domain with lipopolysaccharide-binding and -neutralizing activity.
AB  - The interaction of lipopolysaccharide with CD14 plays a key role in signaling
      that activates an early defense against pathogens but also contributes to the
      development of sepsis and septic shock. Here we have mapped the entire 356-amino
      acid protein with synthetic 20-amino-acid peptides and have identified a new
      lipopolysaccharide-binding domain with a strong LPS-neutralizing activity.
      Moreover, analysis of the structure-activity relationship of this peptide, which
      corresponds to amino acids 81-100 of human CD14, revealed that leucines 87, 91,
      and 94 are essential for these activities. The functional relevance of these
      residues was confirmed by cellular expression of mutant CD14 proteins that are no
      longer able to bind LPS. Furthermore, the peptide provided a basis for the
      generation of highly soluble analogues with stronger lipopolysaccharide
      neutralizing activity.

PMID- 16444758
TI  - C-terminal modifications of a protein by UAG-encoded incorporation of puromycin
      during in vitro protein synthesis in the absence of release factor 1.
AB  - Deactivation of release factor 1 by polyclonal antibodies in an in vitro
      translation system, which was used to express the esterase gene, led to the
      reversible elimination of naturally occurring termination. This technique allowed
      the antibiotic puromycin to be used as an acceptor substrate for the peptidyl
      residue in the peptidyl-transferase reaction. This resulted in more than 80 %
      yield of protein with C-terminally incorporated puromycin. pCpPuromycin that was
      either conjugated with the Cy3 fluorophor or biotin by N4 alkylation of cytosine,
      also acted as an acceptor substrate for the peptidyl-transferase reaction and was
      incorporated into the protein C terminus. The resulting conjugates possessed Cy3
      specific fluorescence and affinity to streptavidin-coated surfaces, respectively.
      This left the enzymatic activity of the reporter protein unaffected. It was also
      shown that extension of puromycin on its 5'-hydroxyl end by up to ten
      deoxyoligonucleotides also allowed conjugation with the C terminus of in vitro
      translated protein when RF1-dependent termination was suppressed. However, the
      conjugation yield decreased upon addition of more than six nucleotides.

PMID- 16444759
TI  - Unexpected oxidation of a depsipeptide substrate analogue in crystalline
      isopenicillin N synthase.
AB  - Isopenicillin N synthase (IPNS) is a non-heme iron(ii)-dependent oxidase that is
      central to penicillin biosynthesis. Herein, we report mechanistic studies of the
      IPNS reaction in the crystalline state, using the substrate analogue delta-(L
      alpha-aminoadipoyl)-(3R)-methyl-L-cysteine D-alpha-hydroxyisovaleryl ester
      (AmCOV) to probe the early stages of the catalytic cycle. The X-ray crystal
      structure of the anaerobic IPNS:Fe(II):AmCOV complex was solved to 1.40 A
      resolution, and it reveals several subtle differences in the active site relative
      to the complex of the enzyme with its natural substrate. The crystalline
      IPNS:Fe(II):AmCOV complex was then exposed to oxygen gas at high pressure; this
      brought about reaction to give what appears to be a hydroxymethyl/ene-thiol
      product. A mechanism for this reaction is proposed. These results offer further
      insight into the delicate interplay of steric and electronic effects in the IPNS
      active site and the mechanistic intricacies of this remarkable enzyme.

PMID- 16444761
TI  - Glucokinase mutations in young children with hyperglycemia.
AB  - BACKGROUND: The etiology of mild hyperglycemia without ketoacidosis in young
      children is often unknown. Maturity onset diabetes of youth (MODY) is a form of
      diabetes mellitus (DM) characterized by fasting hyperglycemia without evidence
      for autoimmune destruction of beta-cells. METHODS: We genetically analyzed four
      families of young children with fasting hyperglycemia with family histories of
      diabetes for mutations in the genes for hepatocyte nuclear factor 4 alpha
      (HNF4alpha), glucokinase (GCK), and hepatocyte nuclear factor 1 alpha
      (HNF1alpha), the genes responsible for MODY1, MODY2, and MODY3, respectively.
      RESULTS: We identified mutations in GCK (Gly258Asp, Arg303Trp, and Arg191Gln) in
      three of the four families. Molecular genetic characterization in these children
      clarified the etiology and prognosis of the hyperglycemia and allowed
      discontinuation of insulin therapy in one family. CONCLUSIONS: We conclude that
      molecular evaluation for MODY in children with mild fasting hyperglycemia without
      ketosis with family histories of diabetes can provide important prognostic
      information to guide therapy and exclude preclinical type 1 diabetes mellitus.

PMID- 16444762
TI  - Consumption costs and earnings during added years of life - a reply to Nyman.

PMID- 16444764
TI  - Emotional distress: the sixth vital sign--future directions in cancer care.

PMID- 16444763
TI  - Metformin delays the manifestation of diabetes and vascular dysfunction in Goto
      Kakizaki rats by reduction of mitochondrial oxidative stress.
AB  - BACKGROUND AND AIM: This study was undertaken to test the hypothesis that
      hyperglycaemia induces the generation of reactive oxygen species (ROS) by
      mitochondria and that the oxidative stress thereby exerted is diminished by
      treatment with metformin. As a parameter of mitochondrial ROS formation, the
      activity of mitochondrial aconitase activity was determined using Goto-Kakizaki
      (GK) rats as model of type 2 diabetes. METHODS: In parallel with the development
      of diabetes (glucose, insulin), the generation of oxidative stress was determined
      in aortic tissue, heart and kidney of GK rats by measurement of lipid peroxides,
      oxidized proteins (carbonyl activity) and mitochondrial aconitase activity.
      Vascular activity was determined in aortae by measuring the endothelium-dependent
      vasodilatation in response to acetylcholine, and vasoconstriction in response to
      phenylephrine. RESULTS: At the age of 12-14 weeks, blood glucose levels rose
      dramatically from 7.5 up to 16.2 mM, indicating the manifestation of an overt
      diabetes. In addition, the glucose tolerance was impaired. The increase in blood
      glucose was not accompanied by changes in plasma insulin. Whereas the lipid
      peroxides in plasma only showed a tendency to increase, the amount of oxidized
      proteins (carbonyl moieties) increased from 4.6 to 10.9 micromol/mg protein (2.4
      fold). In addition, the lipid peroxides in tissue were increased. Mitochondrial
      aconitase activity was reduced in the aorta and kidney, but not in the heart of
      diabetic animals. Treatment with metformin nearly normalized the hyperglycaemia
      and prevented the rise in carbonyl, tissue lipid peroxides and the fall in
      aconitase activity. Whereas the endothelium-dependent vasodilatation was not
      affected by the diabetes, the reaction of aortae in response to phenylephrine was
      strongly enhanced, changes which were prevented by treatment with metformin.
      CONCLUSIONS: These observations provide in vivo evidence that the generation of
      ROS plays an important role in the onset of diabetes and the development of
      vascular dysfunction in GK rats with type 2 diabetes.

PMID- 16444765
TI  - Lipid peroxidation in liver tissue of ovariectomized and pinealectomized rats:
      effect of estradiol and progesterone supplementation.
AB  - The present study aimed to determine the effect of estradiol-progesterone
      supplementation and pinealectomy on lipid peroxidation of liver tissue in
      ovariectomized rats. The study was carried out on 36 adult Sprague-Dawley female
      rats, which weighed 200-250 g. The rats were divided into 6 groups: Group 1: Sham
      Ovariectomy (Sham-Ovx), Group 2: Ovariectomy (Ovx), Group 3: Ovx + Estradiol
      Progesterone supplementation (Ovx + H), Group 4: Sham Pinealectomy and Ovx (Sham
      Pnx -Ovx), Group 5: Ovx -Pnx, Group 6: Ovx -Pnx + H. Malondialdehyde (MDA),
      reduced form of glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were
      determined in liver tissue of rats. The highest MDA levels and the lowest GSH-Px
      levels were determined in the ovariectomized-pinealectomized group, whereas the
      lowest MDA was in the Sham-Ovx group, and the highest GSH-Px levels were found in
      the Sham-Ovx and Ovx + Hormone supplemented group. Furthermore, the highest GSH
      levels were in group 1 and lowest levels were in group 5. The findings of this
      study demonstrate that ovariectomy led to lipid peroxidation in liver tissues of
      rats. Pinealectomy in addition to ovariectomy, increases lipid peroxidation, but,
      estradiol and progesterone supplementations to the ovariectomized-pinealectomized
      rats protect against lipid peroxidation to a significant extent.

PMID- 16444766
TI  - A novel missense mutation in ADRB3 increases risk for type 2 diabetes in a
      Mexican American family.
AB  - BACKGROUND: The human beta3-adrenergic receptor gene (ADRB3) has been
      investigated as a candidate gene for diabetes-related traits in many studies.
      However, the results have been inconsistent so it is unclear whether variation in
      ADRB3 is a risk factor for type 2 diabetes. We have identified a novel missense
      mutation of ADRB3 in a single large pedigree of the San Antonio Family
      Diabetes/Gallbladder Study (SAFDGS) that is located in the first transmembrane
      domain at amino acid 62 (Ile62Met). The aim of this study was to investigate the
      association of this mutation in the SAFDGS with risk for diabetes. METHODS:
      Variance components-based statistical methods were used to determine association
      of this mutation with diabetes traits in the SAFDGS. The ADRB3 gene was also
      resequenced to identify all variants present in this pedigree. RESULTS:
      Significant association was observed for the Ile62Met mutation and type 2
      diabetes (p = 0.01, relative risk 2.3), an earlier age of onset (p = 0.01) and 2
      h glucose measures (p = 0.006) in the single pedigree. Average age and body mass
      index do not differ between the two genotypic groups. In a recent genome-wide
      linkage analysis of SAFDGS, we observed suggestive linkage of diabetes to this
      region at marker D8S1477 (2pt LOD of 2.55). The variance attributed to Ile62Met
      accounted for nearly all of the family-specific LOD score. CONCLUSIONS: These
      results suggest that this variant in ADRB3 is influencing diabetes risk in this
      Mexican American family and supports a role for alterations of the beta3
      adrenergic receptor in the pathogenesis of type 2 diabetes.

PMID- 16444767
TI  - Protective effect of cerebrocrast on rat brain ischaemia induced by occlusion of
      both common carotid arteries.
AB  - Diabetes mellitus is accompanied by several cardiovascular complications
      including atherosclerosis, cerebral ischaemia and stroke. We examined the
      neuroprotective effect of a 1,4-dihydropyridine derivative cerebrocrast (C, a new
      antidiabetic agent, synthesized in the Latvian Institute of Organic Synthesis) on
      the level of ATP in the brain, and on changes of the EEG and ECG, as well as
      blood pressure parameters in anaesthetized Wistar male rats before and during 10
      min occlusion of both common carotid arteries. Cerebrocrast was administered i.v.
      at doses of 1.0 and 10 microg/kg in the v. femoralis 20 min prior to ischaemia.
      After 10-min ischaemia animals were decapitated and the brain was immediately
      frozen in liquid nitrogen and subsequently used for analysis of changes of ATP
      contention. Cerebrocrast, administered at doses of 1.0 and 10 microg/kg 20 min
      prior to occlusion of both common carotid arteries, completely prevented a fall
      in the ATP content of brain compared with the control rats. In control rats the
      content of ATP in brain during ischaemia decreased from 2.77 +/- 0.22 (basal
      level) to 1.74 +/- 0.20 micromol/g as a result of ischaemia. By administration of
      cerebrocrast 20 min before occlusion of the arteries, the content of ATP in the
      brain remained at the level of preischaemia (1.0 microg/kg C + ischaemia 2.82 +/-
      0.36; 10 microg/kg C + ischaemia 2.42 +/- 0.22 micromol/g). Analysis of EEG
      parameters both before and during 10 min of occlusion showed that at a C dose of
      1.0 microg/kg before occlusion produced a regular alpha rhythm during ischaemia
      and prevented cerebral bioelectric activity from significant changes. The
      depression of basal rhythm was observed at a C dose of 10 microg/kg during
      ischaemia in two rats out of six as well as an increase in the ECG ST segment
      above the isoelectric line. Blood pressure was decreased by about 10-20 mm Hg. We
      propose that pretreatment of rats with cerebrocrast at doses of 1.0 or 10
      microg/kg 20 min prior to ischaemia can prevent ischaemic damage of rat brain,
      maintain necessary energy consumption, promote ATP production in brain cells, and
      prevent significant changes in EEG and ECG parameters. These properties are
      important in diabetes mellitus and its evoked cardiovascular complications as
      stroke, ischaemia, etc.

PMID- 16444768
TI  - Miniaturization of microwave-assisted carbohydrate functionalization to create
      oligosaccharide microarrays.

PMID- 16444769
TI  - Convergent glycopeptide synthesis by traceless Staudinger ligation and enzymatic
      coupling.

PMID- 16444770
TI  - Monitoring chemical reactions by using ion-channel-forming peptides.

PMID- 16444771
TI  - 'Hy's law,' the 'Rezulin Rule,' and other predictors of severe drug-induced
      hepatotoxicity: putting risk-benefit into perspective.

PMID- 16444772
TI  - Dopamine challenge tests as an indicator of psychological traits.
AB  - After discussing some introductory considerations about the value of challenge
      tests in general for discriminating personality dimensions which are considered
      extrapolations of psychopathological diseases, the present paper outlines the
      matter of responsivity to agonistic and antagonistic dopaminergic drugs or drugs
      of different mechanisms of action in the dopaminergic system, and elucidates that
      different hormones elicited by dopaminergic substances (prolactin, growth
      hormone) may indicate personality related differences in susceptibility of
      different brain areas. A further point was to demonstrate not only the well known
      relationship of dopaminergic hyperactivity with reward seeking and motivational
      factors associated with extraversion and novelty seeking, but also the
      relationship of dopaminergic hypofunction with the personality dimension of
      depression which had already been reported in studies on animals and psychiatric
      patients. A final point was to demonstrate that besides size of hormone responses
      additional parameters like time of response onset and initial prolactin increase
      can be used as biochemical indicators for identifying certain personality types,
      like highly depressive neurotic persons characterized by lower and later dopamine
      responses as compared to low depressives, and extraverted sensation-seeking types
      responding by an initial prolactin peak as opposed to low sensation seekers.

PMID- 16444773
TI  - Signalling pathways evoked by alpha1-adrenoceptors in human melanoma cells.
AB  - The biological effects of catecholamines in mammalian pigment cells are poorly
      understood, but in poikilothermic vertebrates they regulate the translocation of
      pigment granules. We have previously demonstrated in SK-Mel 23-human melanoma
      cells the presence of low affinity alpha(1)-adrenoceptors, which mediate a
      decrease in cell proliferation and increase in tyrosinase activity, with no
      change of tyrosinase expression. In this report, we investigated the signalling
      pathways involved in these responses. Calcium mobilization in response to
      phenylephrine (PHE), an alpha(1)-adrenergic agonist, was investigated by confocal
      microscopy, and no change of fluorescence during the treatment was observed,
      suggesting that calcium is not involved in the signalling pathway activated by
      alpha(1)-adrenoceptors in SK-Mel 23 cells. cAMP levels, determined by enzyme
      immunoassay, were significantly increased by PHE (10(-5)-10(-4)M), that could be
      blocked by the alpha(1)-adrenergic antagonist benoxathian (10(-5)-10(-4)M).
      Several biological assays were then performed with PHE, for 72 h, in the absence
      or presence of various signalling pathway inhibitors, in an attempt to determine
      the intracellular messengers involved in the responses of proliferation and
      tyrosinase activity. Our results suggest the participation of p38 and ERKs in PHE
      induced decrease of proliferation, and possibly also of cAMP and protein kinase
      A. Regarding PHE-induced increase of tyrosinase activity, it is suggested that
      the following signalling components are involved: cAMP/PKA, PKC, PI3K, p38 and
      ERKs.

PMID- 16444774
TI  - Enantioselective synthesis of 2-aryl cyclopentanones by asymmetric epoxidation
      and epoxide rearrangement.

PMID- 16444775
TI  - Polymer therapeutics: concepts and applications.
AB  - Polymer therapeutics encompass polymer-protein conjugates, drug-polymer
      conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein
      conjugates with improved stability and pharmacokinetic properties have been
      developed, for example, by anchoring enzymes or biologically relevant proteins to
      polyethylene glycol components (PEGylation). Several polymer-protein conjugates
      have received market approval, for example the PEGylated form of adenosine
      deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular
      weight polymers through a cleavable linker is an effective method for improving
      the therapeutic index of clinically established agents, and the first candidates
      have been evaluated in clinical trials, including, N-(2
      hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel,
      and platinum(II) complexes. Another class of polymer therapeutics are drug
      delivery systems based on well-defined multivalent and dendritic polymers. These
      include polyanionic polymers for the inhibition of virus attachment, polycationic
      complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures
      for the encapsulation of drugs. In this Review an overview of polymer
      therapeutics is presented with a focus on concepts and examples that characterize
      the salient features of the drug-delivery systems.

PMID- 16444778
TI  - Effects of sulfonylureas on mitochondrial ATP-sensitive K+ channels in cardiac
      myocytes: implications for sulfonylurea controversy.
AB  - BACKGROUND: Mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel plays a key
      role in cardioprotection. Hence, a sulfonylurea that does not block mitoK(ATP)
      channels would be desirable to avoid damage to the heart. Accordingly, we
      examined the effects of sulfonylureas on the mitoK(ATP) channel and mitochondrial
      Ca(2+) overload. METHODS: Flavoprotein fluorescence in rabbit ventricular
      myocytes was measured to assay mitoK(ATP) channel activity. The mitochondrial
      Ca(2+) concentration was measured by loading cells with rhod-2. RESULTS: The
      mitoK(ATP) channel opener diazoxide (100 microM) reversibly increased
      flavoprotein oxidation to 31.8 +/- 4.3% (n = 5) of the maximum value induced by
      2,4-dinitrophenol. Glimepiride (10 microM) alone did not oxidize the
      flavoprotein, and the oxidative effect of diazoxide was unaffected by glimepiride
      (35.4 +/- 3.2%, n = 5). Similarly, the diazoxide-induced flavoprotein oxidation
      was unaffected both by gliclazide (10 microM) and by tolbutamide (100 microM).
      Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and
      the intensity of rhod-2 fluorescence increased to 197.4 +/- 7.2% of baseline (n =
      11). Treatment with diazoxide significantly reduced the ouabain-induced
      mitochondrial Ca(2+) overload (149.6 +/- 5.1%, n = 11, p < 0.05 versus ouabain
      alone), and the effect was antagonized by the mitoK(ATP) channel blocker 5
      hydroxydecanoate (189.8 +/- 27.8%, n = 5) and glibenclamide (193.1 +/- 7.7%, n =
      8). On the contrary, cardioprotective effect of diazoxide was not abolished by
      glimepiride (141.8 +/- 7.8%, n = 6), gliclazide (139.0 +/- 9.4%, n = 5), and
      tolbutamide (141.1 +/- 4.5%, n = 7). CONCLUSIONS: Our results indicate that
      glimepiride, gliclazide, and tolbutamide have no effect on mitoK(ATP) channel,
      and do not abolish the cardioprotective effects of diazoxide. Therefore, these
      sulfonylureas, unlike glibenclamide, do not interfere with the cellular pathways
      that confer cardioprotection.

PMID- 16444779
TI  - Propionate inhibits glucose-induced insulin secretion in isolated rat pancreatic
      islets.
AB  - Dietary fibers, probably by generating short chain fatty acids (SCFA) through
      enterobacterial fermentation, have a beneficial effect on the control of glycemia
      in patients with peripheral insulin resistance. We studied the effect of
      propionate on glucose-induced insulin secretion in isolated rat pancreatic
      islets. Evidence is presented that propionate, one of the major SCFA produced in
      the gut, inhibits insulin secretion induced by high glucose concentrations (11.1
      and 16.7 mM) in incubated and perfused pancreatic islets. This short chain fatty
      acid reduces [U-(14)C]-glucose decarboxylation and raises the conversion of
      glucose to lactate. Propionate causes a significant decrease of both [1-(14)C]-
      (84%) and [2-(14)C]-pyruvate (49%) decarboxylation. These findings indicate
      pyruvate dehydrogenase as the major site for the propionate effect. These
      observations led us to postulate that the reduction in glucose oxidation and the
      consequent decrease in the ATP/ADP ratio may be the major mechanism for the lower
      insulin secretion to glucose stimulus induced by propionate.

PMID- 16444780
TI  - An allosterically regulated molecular shuttle.

PMID- 16444781
TI  - The chlorination of the [Al13]- cluster and the stepwise formation of its
      intermediate products, [Al11]-, [Al9]-, and [Al7]-: a model reaction for the
      oxidation of metals?

PMID- 16444783
TI  - Formation of heteroatom active sites in zeolites by hydrolysis and inversion.

PMID- 16444782
TI  - Abasic-site-containing oligodeoxynucleotides as aptamers for riboflavin.

PMID- 16444784
TI  - Emission enhancement by formation of aggregates in hybrid chromophoric surfactant
      amphiphile/silica nanocomposites.

PMID- 16444786
TI  - Enhanced collective electron transport by CdSe quantum dots confined in the
      poly(4-vinylpyridine) nanodomains of a poly(styrene-b-4-vinylpyridine) diblock
      copolymer thin film.

PMID- 16444785
TI  - Artemisone--a highly active antimalarial drug of the artemisinin class.

PMID- 16444787
TI  - Synthesis of functionalized cyclopentenes through catalytic asymmetric [3+2]
      cycloadditions of allenes with enones.

PMID- 16444788
TI  - Amino acid derived macrocycles--an area driven by synthesis or application?
AB  - The synthesis, structure, and physical properties of macrocycles have fascinated
      chemists for many years. Their inherent properties make them useful in areas as
      diverse as ion transport across membranes, development of new antibiotics, and
      catalysis. In this Review, the authors examine the chemistry of macrocycles
      containing non-peptidic amino acid derived molecules; the analysis is discussed
      in terms of function, rather than structure or synthesis. It is revealed that the
      diverse and imaginative structures created by synthetic chemists are not being
      fully exploited in application-driven endeavors.

PMID- 16444789
TI  - A chiral [2]catenane precursor of the antiarthritic gold(I) drug auranofin.

PMID- 16444790
TI  - Guest exchange in single crystals of van der Waals nanocapsules.

PMID- 16444791
TI  - Rigid-rod metallosupramolecular polymers of dendronized diazadibenzoperylene
      dyes.

PMID- 16444792
TI  - Selective carbonylation of dimethyl ether to methyl acetate catalyzed by acidic
      zeolites.

PMID- 16444793
TI  - Enantiomerically enriched allylglycine derivatives through the catalytic
      asymmetric allylation of iminoesters and iminophosphonates with allylsilanes.

PMID- 16444794
TI  - Microwave-promoted rhodium-catalyzed arylation of heterocycles through C--H bond
      activation.

PMID- 16444795
TI  - Mirtazapine naturalistic depression study (in Sweden)--MINDS(S): clinical
      efficacy and safety.
AB  - OBJECTIVE: To study how implementation of a naturalistic trial design for
      mirtazapine treatment in major depressive disorder for six (up to 12) months
      could be used and evaluated by means of clinical efficacy and safety. METHOD: An
      open-labelled, prospective, multicenter, non-comparative trial was conducted
      during a 2-year period in patients with major depression according to DSM-IV
      treated in psychiatric departments and primary care in Sweden. Minimal inclusion
      and exclusion criteria were used in order to diminish the potential patient
      selection bias. Maximum flexibility of the dosage of mirtazapine was allowed, and
      clinical assessments included MADRS, CGI, vital signs and spontaneous reporting
      of adverse events. RESULTS: 192 patients were found eligible and enrolled in the
      study. A significant improvement in depressive symptoms according to MADRS and
      CGI was observed including particularly marked sleep improvement early in the
      treatment. Slight increases in body weight and BMI were observed. The
      investigational drug was well tolerated overall. CONCLUSION: The clinical
      efficacy and safety of mirtazapine found in this naturalistic setting is in line
      with previously reported data on mirtazapine in traditional controlled clinical
      trials. The results confirm that the naturalistic study design facilitated
      conduct of the trial. The authors suggest that this type of study design should
      also be applied to other antidepressant drugs that are frequently prescribed in
      the general population.

PMID- 16444796
TI  - Development of the Vaccine Analytic Unit's research agenda for investigating
      potential adverse events associated with anthrax vaccine adsorbed.
AB  - PURPOSE: In 2002, the Centers for Disease Control and Prevention established the
      Vaccine Analytic Unit (VAU) in collaboration with the Department of Defense
      (DoD). The focus of this report is to describe the process by which the VAU's
      anthrax vaccine safety research plan was developed following a comprehensive
      review of these topics. METHODS: Public health literature, surveillance data, and
      clinical sources were reviewed to create a list of adverse events hypothesized to
      be potentially related to anthrax vaccine adsorbed (AVA). From this list, a
      consensus process was used to select 11 important research topics. Adverse event
      background papers were written for each of these topics, addressing predetermined
      criteria. These were independently reviewed and ranked by a National Vaccine
      Advisory Committee (NVAC) workgroup. The adverse events included in the final
      priority list will be the subject of observational or other post marketing
      surveillance studies using the Defense Medical Surveillance System (DMSS)
      database. RESULTS: A review of various information sources identified over 100
      potential adverse events. The review process recommended 11 topics as potentially
      warranting further study. The NVAC workgroup identified the following adverse
      event topics for study: arthritis, optic neuritis, and Stevens-Johnson
      syndrome/Toxic epidermal necrolysis. Two additional topics (systemic lupus
      erythematosus (SLE) and multiple, near-concurrent military vaccinations) were
      added in response to emerging public health and military concerns. CONCLUSIONS:
      The experience described, while specific for establishing the VAU's research
      agenda for the safety of the current anthrax vaccine, may be useful and adapted
      for research planning in other areas of public health research.

PMID- 16444797
TI  - Electron ionization induced mass spectral study of new isomeric 2-o- (m- and p
      )nitrobenzylthio-5-piperidinomethyl(morpholinomethyl)uracils and 1,2-di-o-(m- and
      p-)nitrobenzyl-5-piperidinomethyl(morpholinomethyl)-2-thiouracils.

PMID- 16444798
TI  - Accelerated on-column lysine derivatization and cysteine methylation by imidazole
      reaction in a deuterated environment for enhanced product ion analysis.
AB  - The combination of separation techniques and mass spectrometry (MS) for peptide
      investigation allows superior sensitivity of detection and richer fragmentation
      data than available by direct MS analysis of a complex mixture. In this regard,
      liquid chromatography (LC) coupled to electrospray ionization (ESI) and matrix
      assisted laser desorption/ionization (MALDI) MS have evolved as versatile
      analytical tools in proteomics. Very often, however, the product ion mass
      spectrum is either incomplete or overfilled with ions, thus making sequence
      analysis difficult. Here we report overall ion intensity improvement of C
      terminal lysine-containing peptides from Lys-C digest by on-column derivatization
      of lysines with 2-methoxy-4,5-dihydro-1H-imidazole. The method is simple, fast
      and exhibits 100% efficiency of the reaction. Additionally, post-source decay
      carried out on derivatized peptides gave rise almost exclusively to y-series ion
      formation, at 100% sequence coverage and high intensity. The novelty of the
      method resides in the side reaction of this derivatization process, namely the
      methylation of cysteines. This facilitates the estimation of the disulfide bridge
      position in a protein and the fragmentation of cysteine-containing peptide
      fragments. Additionally, by using this derivatization procedure, the loss of
      peptides, their degradation and/or oxidation, usually occurring in digest
      alkylation procedures, is greatly minimized. The new on-column derivatization
      protocol is designed to be carried out on C18 Spin Tubes or Cleanup C18 Pipette
      Tips. We observed that use of buffered D2O solvent prevented unwanted oxidation
      and degradation reactions with respect to the stationary phase. This may be due
      to the fact that a deuteron is less polar than a proton, and thus the bonded
      silica stationary phase saturated with deuterons does not affect the reaction
      between epsilon-amino or cysteine thiol groups and 2-methoxy-4,5-dihydro-1H
      imidazole. Complete tagging of the peptides by on-column reaction could be
      obtained when using D2O, as compared to water-based reaction. Methylation of
      cysteine residues was enhanced when beta-mercaptoethanol was added in the
      reactant solution.

PMID- 16444799
TI  - Electrospray ionization tandem mass spectrometric analysis of fragmentation
      patterns of dithiocarbamate derivatives.

PMID- 16444800
TI  - Monitoring enzyme-catalyzed production of glucosamine-6P by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry: a new enzymatic assay for
      glucosamine-6P synthase.
AB  - A matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS) method for quantification of D-glucosamine-6P (GlcN-6P) that allows
      the kinetic study of glucosamine-6P synthase (Glms) is presented. The present
      report describes the optimization of the different steps of a new enzymatic assay
      for Glms based on in situ N-acetylation of GlcN-6P and MALDI-TOFMS analysis using
      N-(13C2)acetylglucosamine-6P as internal standard. Since no isotopically
      substituted GlcN-6P was available, the N-(13C2)acetyl derivative, easily obtained
      from (13C4)-acetic anhydride, was used as internal standard. Validation of the
      assay was achieved by measuring the fructose-6P Michaelis constant, in full
      agreement with reported values, and by studying the inhibition properties of
      arabinose-5P oxime.

PMID- 16444801
TI  - Three Bs for the brain.

PMID- 16444802
TI  - NSAIDs side effects.

PMID- 16444803
TI  - "Bad" cholesterol: very low is better--and safe.

PMID- 16444805
TI  - I cam across a report in my medical records that said I had severe diastolic
      dysfunction. What does that mean and what should I do about it?

PMID- 16444804
TI  - Blood pressure drugs prevent headaches.

PMID- 16444806
TI  - What's the difference between stable and unstable plaque? Is there any way I can
      find out whether the plaque in my arteries is unstable?

PMID- 16444807
TI  - Coffee may reduce risk of liver cancer.

PMID- 16444808
TI  - Bone transplants. Many options for repair.

PMID- 16444809
TI  - I'm taking Zocor to help lower my cholesterol. The directions say to take it at
      night. My friend takes Lipitor, but doesn't have to take it at night. Why the
      difference?

PMID- 16444810
TI  - Incidence and outcomes of acute lung injury.

PMID- 16444811
TI  - Low HDL cholesterol levels.

PMID- 16444812
TI  - Low HDL cholesterol levels.

PMID- 16444813
TI  - Low HDL cholesterol levels.

PMID- 16444814
TI  - Immunocytochemical evidence that most sensory neurons of the rat molar pulp
      express receptors for both glial cell line-derived neurotrophic factor and nerve
      growth factor.
AB  - Most pulpal afferent neurons have cytochemical features in common with the class
      of nociceptors that express neuropeptides and respond to NGF, while very few bind
      the plant lectin IB4, a widely used marker for the class of nociceptors that
      respond to the GDNF family of neurotrophic factors. The present study was
      undertaken to determine whether the GDNF receptor, GFRalpha-1, is expressed by
      pulpal afferents, and, further, to determine whether tooth injury evokes changes
      in expression of the GDNF and NGF receptors among pulpal afferents. The tracer,
      fluoro-gold (FG), was applied to shallow cavities in dentin of first and second
      maxillary molars. After 4 weeks, the molars of one side received a test injury
      consisting of a deeper cavity that exposed pulp horns. Animals were perfusion
      fixed 2 days later, and sections of the trigeminal ganglia were double
      immunostained with combinations of antibodies against GFRalpha-1, and TrkA. Under
      control conditions, GFRalpha-1 immunostaining was observed in 72% of neurons that
      projected to the molar pulp, TrkA in 78%, and immunostaining for both receptors
      was observed in 65% of pulpal afferents. Tooth injury evoked up-regulation of
      GFRalpha-1 expression (to 93%) and a slight down-regulation of TrkA expression
      (67%) among tooth afferents, while there was no discernable change in the
      proportion of pulpal afferents that expressed both TrkA and GFRalpha-1 (to 61%).

PMID- 16444815
TI  - Is glycine effective against elevated blood pressure?
AB  - PURPOSE OF REVIEW: Glycine, a non-essential amino acid, has been found to protect
      against oxidative stress in several pathological situations, and it is required
      for the biosynthesis of structural proteins such as elastin. As hypertension is a
      disease in which free radicals and large vessel elasticity are involved, this
      article will examine the possible mechanisms by which glycine may protect against
      high blood pressure. RECENT FINDINGS: The addition of glycine to the diet reduces
      high blood pressure in a rat model of the metabolic syndrome. Also, glycine
      supplemented to the low protein diet of rat dams during pregnancy has a
      beneficial effect on blood pressure in their offspring. The mechanism by which
      glycine decreases high blood pressure can be attributed to its participation in
      the reduction of the generation of free radicals, increasing the availability of
      nitric oxide. In addition, as glycine is required for a number of critical
      metabolic pathways, such as the synthesis of the structural proteins collagen and
      elastin, the perturbation of these leads to impaired elastin formation in the
      aorta. This involves changes in the aorta's elastic properties, which would
      contribute to the development of hypertension. SUMMARY: The use of glycine to
      lower high blood pressure could have a significant clinical impact in patients
      with the metabolic syndrome and with limited resources. On the other hand, more
      studies are needed to explore the beneficial effect of glycine in other models of
      hypertension and to investigate possible side-effects of treatment with glycine.

PMID- 16444816
TI  - Taurine supplementation and diabetes mellitus.
AB  - PURPOSE OF REVIEW: Taurine is a semi-essential sulphur amino acid derived from
      methionine and cysteine metabolism. It has been evaluated either in experimental
      or clinical type 1 and 2 diabetes mellitus and insulin resistance. One form of
      experiment has included the possibility that perinatal taurine administration
      could prevent diabetes mellitus and/or insulin resistance. RECENT FINDINGS:
      Experimental data suggest strongly that taurine could have beneficial effects in
      type 1 diabetes mellitus, and could generally reduce organ lipid peroxidation and
      plasma lipids. Interestingly, retina, lens and nerves seem to respond better to
      taurine than other organs such as kidneys. It has been shown in some experimental
      models that in type 2 diabetes mellitus and insulin resistance there is
      alteration in taurine homeostasis. Taurine could prevent the onset of diabetes
      mellitus in NOD mice and postnatal taurine modifies the glucose-loading curves in
      adults. However, the clinical studies are too small and too short to have any
      real significance. SUMMARY: Further experimental and clinical studies are
      required to evaluate taurine's possible therapeutic potential. Careful attention
      has to be paid in the selection of animal species, in standardization of taurine
      concentrations and patient selection. Moreover, care must also be given to the
      metabolic state, presence of complications, duration of supplementations and
      selection of the right end-points.

PMID- 16444817
TI  - Synthesis and absorption of intestinal microbial lysine in humans and non
      ruminant animals and impact on human estimated average requirement of dietary
      lysine.
AB  - PURPOSE OF REVIEW: While there are reports on the nature of synthesis and
      absorption of intestinal microbial lysine in humans and non-ruminant animals,
      there are few efforts to quantify microbial amino acid absorption in human
      subjects. We review the available information on the synthesis of microbial
      lysine and the quantification of its absorption and utilization by the human host
      and monogastric model animals. In addition, we explore the impact of microbial
      lysine on the current estimated average requirement of dietary lysine. RECENT
      FINDINGS: It is still uncertain whether microbial amino acids are absorbed
      primarily from the small or the large intestine in humans. In the pig, the
      majority of microbial lysine is absorbed in the small intestine. It appears that
      microbial lysine contribution is responsive to the nutritional status of the
      host. Estimates for microbial lysine contribution in adult humans on adequate or
      low protein diets range from 12 to 68 mg/kg per day. It is unlikely that these
      estimates represent net values because of methodological concerns related to the
      15N tracer methodology used. SUMMARY: We conclude that microbial lysine
      contributes to the lysine homeostasis in humans and other non-ruminant mammals.
      Microbial lysine utilization by the host is a continuous process and occurs both
      with low, adequate, and high protein intakes, and under protein-free and low
      lysine dietary conditions in growing and adult individuals. We also conclude that
      the estimated average lysine requirement for humans already considers lysine
      contributed by the intestinal microbiota.

PMID- 16444818
TI  - Influence of proteasome inhibitors on apoptosis.
AB  - PURPOSE OF REVIEW: Proteasome inhibitors are a novel class of drugs that alter
      normal cellular control of apoptosis. As such, they are being investigated as
      novel therapies to alter uncontrolled cellular proliferation and treat cancers.
      This review explores new information about how the proteasome regulates apoptosis
      and how proteasome inhibitors can be exploited as anti-tumor drugs. RECENT
      FINDINGS: Proteasome inhibitors block the activation of nuclear factor kappa B in
      a number of cell systems, as well as altering apoptotic regulatory proteins and
      intracellular signals that influence the fate of the cell. These effects are true
      for many tumor cell lines. The US Food and Drug Administration-approved
      proteasome inhibitor bortezomib blocks erroneous cell proliferation and induces
      apoptosis in many tumor models. SUMMARY: Proteasome inhibitors have demonstrated
      promise in vitro, and as a result clinical trials have begun to investigate these
      agents as therapy for numerous human cancers. Furthermore, newer agents are being
      designed to inhibit the proteasome system and exert further anti-tumor activity.

PMID- 16444819
TI  - Integration of amino acid metabolism during intense lactation.
AB  - PURPOSE OF REVIEW: This review focuses on research from the author's laboratory
      and that of N.L. Trottier concerning protein and amino acid metabolism during
      intense lactation, a physiological state characterized by high rates of the net
      transfer of amino acids from physiological reserves in skeletal muscle to the
      mammary gland. These studies have broader interest for our understanding of the
      supply and distribution of amino acids towards key processes. RECENT FINDINGS:
      The synthesis of milk protein occurs at a distinct anatomical location, such that
      arterio-venous differences may be employed to identify all amino acid inputs into
      the mammary gland. These approaches can be used to determine the relative
      contributions to the mammary amino acid supply of systemic amino acid
      availability, transport system regulation and blood flow. Milk protein synthesis
      is partly reliant on the mobilization of endogenously stored protein in skeletal
      muscle, and our ability to modulate the size of physiological protein reserves
      and their rate of mobilization in an experimental context can be used to clarify
      the regulatory events that underlie the access to and eventual depletion of
      skeletal muscle protein. SUMMARY: Massive rates of milk production are achieved
      by increased mammary blood flow and amino acid extraction. Muscle protein
      mobilization is a key resource in the overall amino acid supply, and the absolute
      size of the protein reserve at parturition is a key factor in supporting
      lactation. The progressive depletion of muscle may ultimately provide
      insufficient substrate to support this process.

PMID- 16444820
TI  - Bibliography. Current world literature. Protein and amino acid metabolism.

PMID- 16444821
TI  - Cardiopulmonary health effects of air pollution: is a mechanism emerging?

PMID- 16444822
TI  - Herpesvirus-associated pulmonary hypertension?

PMID- 16444823
TI  - Self assessment exercises in emergency medicine. Question 2. Post-coital
      contraception.

PMID- 16444824
TI  - Self assessment exercises in emergency medicine. Question 3. Exertional heat
      illness.

PMID- 16444825
TI  - Self assessment exercises in emergency medicine. Question 4. Spontaneous
      pneumothorax secondary to a rupture of subpleural bleb.

PMID- 16444826
TI  - Self assessment exercises in emergency medicine. Question 5. Head and neck burns
      with evidence of airway involvement.

PMID- 16444829
TI  - Good bacteria for GI disorders.

PMID- 16444830
TI  - Relief is at hand for carpal tunnel syndrome.

PMID- 16444832
TI  - Taking control of dizziness.

PMID- 16444833
TI  - Controversial new recommendations to prevent SIDS.

PMID- 16444831
TI  - Heart failure: early treatment is key.

PMID- 16444834
TI  - Child safety. Giving epinephrine for serious allergic reactions in school
      settings.

PMID- 16444835
TI  - Is Gatorade a good alternative for treating diarrhea?

PMID- 16444836
TI  - Anxiety disorders. Taking control of persistent worries, fears and phobias.

PMID- 16444837
TI  - Woodward v. Commissioner of Social Security.

PMID- 16444838
TI  - MSMA looks ahead to active 2006 legislative session.

PMID- 16444839
TI  - Reflections on 2005 & a preview of 2006.

PMID- 16444840
TI  - The article of Torregrosa JV et al. is virtually identical to the previous
      publication of Arlen DJ et al.

PMID- 16444841
TI  - Bibliography. Current world literature. Cystic fibrosis.

PMID- 16444842
TI  - KSF post outlines.

PMID- 16444843
TI  - Practical ethics. Does weight matter?

PMID- 16444844
TI  - Bugs behaving badly. Antibiotics are aging, and bacteria are learning to fight
      them off.

PMID- 16444846
TI  - Too slow for cancer.

PMID- 16444845
TI  - Want to help? Just say 'whoa'.

PMID- 16444847
TI  - Pathophysiology and management of fever.
AB  - The febrile response is a complex physiologic reaction to disease involving a
      cytokine-mediated rise in body temperature, generation of acute-phase reactants,
      and activation of numerous endocrinologic and immunologic systems. Understanding
      the basic mechanisms underlying this phenomenon helps to formulate rational
      approaches to treatment and interventions. In this article, the authors review
      the basic pathophysiology of fever, its contributing etiologies, and management
      approaches based on current evidence.

PMID- 16444848
TI  - Pathophysiology and management of fever--we know less than we should.

PMID- 16444849
TI  - Domestic violence against women with cancer: examples and review of the
      literature.
AB  - Over a recent 3-month period in our oncology practice, we became aware of
      multiple patients reporting domestic abuse. We present three selected cases,
      review the literature on domestic violence, and explore issues of diagnosis and
      management in a cancer population. Domestic violence against cancer patients may
      be more common than initially appreciated, and further awareness and research are
      indicated.

PMID- 16444850
TI  - Cancer patients and domestic violence: providing safety and support.

PMID- 16444851
TI  - Measuring the maintenance of daily life activities using the functional living
      index-emesis (FLIE) in patients receiving moderately emetogenic chemotherapy.
AB  - Healthcare providers believe they have a positive impact on controlling
      chemotherapy-induced nausea and vomiting (CINV), yet patients still consider CINV
      to be one of the most distressing side effects of chemotherapy. The effect of
      CINV on daily activities has been measured using the Functional Living Index
      Emesis (FLIE) scale, a validated, nausea- and vomiting-specific, patient-reported
      outcome instrument comprising nine items in each of two domains. This research
      explores the potential correlation between reducing CINV and improved quality of
      life. In clinical trials, patients completed the FLIE questionnaires 24 and 96
      hours after receiving moderately emetogenic chemotherapy and antiemetic therapy
      using a serotonin receptor antagonist (ondansetron, dolasetron, or palonosetron).
      Significantly more patients given palonosetron had FLIE scores that reflected
      lessened impact of nausea on daily life during the acute period (0-24 hours) and
      of nausea/vomiting during both the acute and delayed periods (days 2-4). These
      findings strongly suggest that better antiemetic prevention allows patients to
      maintain their functional status for up to 5 days after chemotherapy.

PMID- 16444852
TI  - How to use antidepressants and anticonvulsants as adjuvant analgesics in the
      treatment of neuropathic cancer pain.

PMID- 16444853
TI  - Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism.
AB  - We investigated the efficacy and safety of extended enoxaparin monotherapy in
      symptomatic patients with acute pulmonary embolism (PE). We randomized 40
      patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for
      10-18 days, and then 1.5mg/kg once daily until day 90) (n = 20) or to enoxaparin
      1.0 mg/kg twice daily as a bridge to warfarin with a target international
      normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin
      overlapping with warfarin for at least 4 days) (n = 20). All patients underwent
      echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing
      to identify patients with an increased likelihood of adverse clinical outcomes.
      The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and
      bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we
      used repeated measure analysis of variance (ANOVA) to investigate differences in
      anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients' mean age was 52 +/
      17 years; the most common comorbidities were obesity (58%), hypertension (30%),
      concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated
      cardiac Tnl >0.1 mg/l and 11 (28%) had moderate or severe right ventricular
      dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a
      continuous infusion of 100 mg alteplase prior to randomization. During a 90-day
      follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic
      distal DVT; one from the warfarin group had recurrent symptomatic PE (p = 1.0).
      None of the study patients had major hemorrhage; two warfarin group patients had
      minor bleeding compared with none in the enoxaparin monotherapy group (p = 0.49).
      Repeated measure ANOVA did not reveal significant differences in anti-Xa levels
      over time (p = 0.217). In patients with acute symptomatic PE, extended enoxaparin
      monotherapy is feasible and warrants further investigation in a large clinical
      trial.

PMID- 16444854
TI  - The association between smoking and the prevalence of intermittent claudication.
AB  - The objective of this study was to investigate the association between smoking
      and the prevalence of intermittent claudication (IC). Between 1995 and 1997, all
      residents aged 20 years or older in Nord-Trondelag County, Norway, were invited
      to take part in the Nord-Trondelag Health Study (Helseundersokelsen i Nord
      Trondelag: HUNT 2). A total of 19748 participants aged 40-69 years attended.
      Responses to 12 questions on IC (including a Norwegian translation of the
      Edinburgh Claudication Questionnaire) had been previously tested against the
      ankle-brachial pressure index (ABPI < 0.9), and an algorithm of the best test
      properties was used to identify people with IC. Using logistic regression
      analysis we computed age-adjusted prevalence odds ratios (OR) for the association
      between smoking and IC. Both current (ORmen = 3.8, confidence interval (CI) 2.1
      6.7, ORwomen = 2.2, CI 1.4-3.4) and former smokers (ORmen = 1.7, CI 0.9-3.2,
      ORwomen = 1.7, CI 1.1-2.7) had a higher prevalence of IC compared with those who
      had never smoked, and individuals who had stopped smoking more than 20 years
      previously had a substantially lower prevalence of IC (ORmen = 0.2, CI 0.1-0.5,
      ORwomen = 0.4, CI 0.2-0.8) than current smokers. We found no association between
      passive smoking and IC in either men or women. Current and previous smoking
      habits were positively associated with the prevalence of IC, and smoking
      cessation was negatively associated in men and women. Passive smoking was not
      associated with IC in this study.

PMID- 16444855
TI  - A pilot study of L-arginine supplementation on functional capacity in peripheral
      arterial disease.
AB  - Peripheral arterial disease (PAD) impairs walking capacity and is often
      associated with a profound endothelial vasodilator dysfunction, characterized by
      reduced bioactivity and/or synthesis of endothelium-derived nitric oxide (NO).
      Previous studies have suggested that dietary supplementation of L-arginine, the
      precursor of NO, improves endothelium-dependent vasodilation, limb blood flow and
      walking distance. However, these studies have been small, and have used large
      intravenous doses of L-arginine. The optimal dose of L-arginine has not been
      determined. Accordingly, this pilot study was conducted to establish the lowest
      effective oral dose of L-arginine to improve walking distance in preparation for
      the definitive study. Patients with PAD and intermittent claudication (n = 80)
      participated in this study. Eligibility criteria included: (1) ankle-brachial
      index (ABI) at rest < or = 0.90; (2) post-exercise reduction in ABI > or = 25%;
      and (3) difference in absolute claudication distance of < or = 25% between two
      consecutive treadmill tests. Treadmill testing was performed using the Skinner
      Gardner protocol and community-based walking was assessed using the walking
      impairment questionnaire. Patients were randomly assigned to oral doses of 0, 3,
      6 or 9 g of L-arginine daily in three divided doses for 12 weeks. Treadmill
      testing was performed prior to administration of the study drug and again after
      12 weeks of treatment. The study drug was well tolerated, with no significant
      adverse effects of L-arginine therapy. The safety laboratory studies were
      unremarkable, except for a statistically significant reduction in hematocrit in
      the L-arginine-treated groups. There was no significant difference observed in
      absolute claudication distance between the groups. However, a trend was observed
      for a greater increase in walking distance in the group treated with 3 g L
      arginine daily, and there was a trend for an improvement in walking speed in
      patients treated with L-arginine. This pilot study provided data for safety, for
      power calculation and for dosing for the larger definitive trial that is now
      underway.

PMID- 16444856
TI  - Vascular compliance versus flow-mediated vasodilation: correlation with
      cardiovascular risk factors.
AB  - Cardiovascular risk factors are associated with impaired endothelium dependent
      vasodilation and reduced vascular compliance. In this study, the correlation with
      cardiovascular risk factor score of two common techniques for assessing vascular
      function was compared. Risk factors and vascular function were evaluated in a
      study population of 122 people with peripheral arterial disease (PAD) or with
      risk factors for PAD (73 men and 49 women; mean age 69 years). A risk factor
      score was determined using Framingham criteria. Vascular compliance was assessed
      by pulse waveform analysis and simultaneous blood pressure measurement. Flow
      mediated vasodilation of the brachial artery was measured using duplex
      ultrasonography. Participants with a high risk factor score had significantly
      reduced vascular compliance of large and small vessels. By contrast, the
      difference in flow-mediated vasodilation between those with a high or low risk
      factor score did not reach statistical significance. There was a significant
      negative correlation between vascular compliance and risk factor score. There was
      a similar trend between flow-mediated vasodilation and risk factor score, but
      this did not reach statistical significance. A measure of vascular compliance was
      more significantly correlated with cardiovascular risk factor score than was a
      measure of flow-mediated vasodilation in the study population. Neither technique
      provided values that were highly correlated with risk factor burden. Although
      flow-mediated vasodilation is a preferred research tool for assessing vascular
      function, technical limitations and biological variability may reduce its
      clinical application in assessing individual cardiovascular risk.

PMID- 16444857
TI  - Effects of local gene transfer of VEGF on neointima formation after balloon
      injury in hypercholesterolemic rabbits.
AB  - Enhancement of the generation of nitric oxide (NO) and vascular endothelial
      growth factor (VEGF) are suggested to prevent restenosis after angioplasty.
      Accordingly, we tested whether the local delivery of L-arginine (L-Arg), a
      substrate for NO generation and the VEGF gene, alone or in combination, can
      influence neointima formation in hypercholesterolemic rabbits. Balloon injury of
      the iliac arteries was performed in 24 New Zealand White rabbits fed a 1%
      cholesterol diet for 3 weeks followed by a local infusion of: (1) pSG5VEGF165
      plasmid alone (1000 microg); (2) pSG5VEGF165 (1000 microg) with L-Arg (800mg);
      (3) L-Arg (800mg) alone; and (4) L-Arg (800 mg) with naked pSVbeta-gal plasmid
      (1000 microg). The animals were kept on the hypercholesterolemic diets for a
      further 28 days, when vessels were taken for morphometric analysis and
      immunocytochemistry. Endogenous rabbit VEGF concentration in the plasma increased
      significantly at 7 days after injury (17.06 +/- 1.57 vs 23.01 +/- 1.9 pg/ml; p <
      0.02) and remained elevated for up to 28 days (28.46 +/- 5.24; p < 0.01). Injured
      arteries exhibited strong immunocytochemical staining for rabbit VEGF. Rabbits
      that received a VEGF gene transfer revealed more prominent neointima formation,
      whereas treatment with L-Arg was associated with significantly less intimal
      thickness (p < 0.05). Local transfer of the VEGF gene does not inhibit neointima
      formation in hypercholesterolemic rabbits. Our results suggest that VEGF gene
      therapy applied locally in atherosclerotic arteries may not be beneficial.

PMID- 16444858
TI  - Mechanisms of Raynaud's disease.
AB  - Raynaud's phenomenon is due to transient cessation of blood flow to the digits of
      the hands or feet. An attack of Raynaud's phenomenon is classically manifested as
      triphasic color changes. The white phase is due to excessive vasoconstriction and
      cessation of regional blood flow. This phase is followed by a cyanotic phase, as
      the residual blood in the finger desaturates. The red phase is due to hyperemia
      as the attack subsides and blood flow is restored. An attack is frequently
      associated with pain and/or paresthesia due to sensory nerve ischemia. Variants
      of Raynaud's phenomenon include acrocyanosis and primary livedo reticularis, each
      of which is associated with reduced skin blood flow, exacerbated by cold or
      emotional upset. Raynaud's phenomenon in the absence of other disorders is
      primary Raynaud's phenomenon, or Raynaud's disease. The mechanisms of Raynaud's
      disease include increased activation of the sympathetic nerves, in response to
      cold or emotion; an impaired habituation of the cardiovascular response to stress
      may contribute. In addition, there appears to be a local fault, which is likely
      multifactorial. This local fault is due to an alteration in vascular function
      rather than vascular structure. The alteration in vascular function may be
      related to increased sensitivity to cold of the adrenergic receptors on the
      digital artery vascular smooth muscle. In some cases, locally released or
      systemically circulating vasoconstrictors may participate, including endothelin,
      5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of
      nitric oxide, possibly due to increased oxidative stress, may be involved in some
      cases. These recent pathophysiological insights may lead to new therapeutic
      options.

PMID- 16444859
TI  - Atheromatous embolization.
AB  - Atheromatous embolization is a multisystem disease complicating advanced
      atherosclerosis. It occurs most often as a complication of angiography, an
      endovascular procedure or cardiovascular surgery. Atheromatous embolization can
      present in a subtle manner where it is often under-recognized, or with
      catastrophic results including myocardial infarction, strake or acute renal
      failure. It may mimic other disease processes and often goes underdiagnosed and
      undertreated. A high clinical suspicion is the key to diagnosis. Atheromatous
      embolization results in significant morbidity and mortality; therefore, early
      recognition followed by aggressive management may help to prevent end-organ
      damage and improve overall clinical outcomes. Management strategies should
      include risk factor modification, prevention of further insults by discontinuing
      or avoiding predisposing factors, supportive treatment and interventional or
      surgical approaches to remove the atheroembolic source. Atheromatous embolization
      is expected to increase as our population ages and the epidemics of diabetes
      mellitus and obesity increase.

PMID- 16444860
TI  - Images in vascular medicine. Iatrogenic thoracic inlet syndrome.

PMID- 16444861
TI  - Images in vascular medicine. Aortic graft pseudo-pseudoaneurysms.

PMID- 16444862
TI  - ADMA: an emerging cardiovascular risk factor.

PMID- 16444863
TI  - Endogenous production of nitric oxide synthase inhibitors.
AB  - Numerous reports have indicated that the plasma concentration of endogenously
      produced inhibitors of nitric oxide synthase are elevated in human disease
      states. In this review we discuss recent advances in our understanding of the
      enzymes responsible for the synthesis of these inhibitors.

PMID- 16444864
TI  - ADMA: its role in vascular disease.
AB  - Endothelium-derived nitric oxide (NO) is the most potent endogenous vasodilator
      and, by virtue of its anti-inflammatory and anti-thrombotic effects, it is an
      endogenous anti-atherogenic agent. Accordingly, impairment of NO synthesis or
      bioactivity may increase the risk of vascular disease. Asymmetric
      dimethylarginine (ADMA) is an endogenous inhibitor of the NO synthase pathway.
      Plasma levels of ADMA are increased in patients with vascular disease, or with
      risk factors for vascular disease. Preclinical and clinical studies indicate that
      ADMA may mediate the adverse effects of traditional risk factors on endothelial
      vasodilator function. By impairing endothelial function, ADMA may contribute to
      pulmonary or systemic hypertension, as well as to vascular disease. Several drugs
      known to treat cardiovascular disease also reduce plasma ADMA levels, such as
      angiotensin receptor antagonists, converting enzyme inhibitors, and insulin
      sensitizing agents. Plasma ADMA may be a common mediator of endothelial
      dysfunction induced by vascular risk factors. Insights into the mechanisms by
      which plasma ADMA is regulated may lead to new therapeutic knowledge.

PMID- 16444865
TI  - Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from
      prospective clinical trials.
AB  - Evidence has accumulated that asymmetric dimethylarginine (ADMA) is an endogenous
      competitive inhibitor of nitric oxide (NO) synthase. ADMA inhibits vascular NO
      production at concentrations found in pathophysiological conditions; it also
      causes local vasoconstriction when infused intra-arterially. ADMA is increased in
      the plasma of humans with hypercholesterolemia, atherosclerosis, hypertension,
      chronic renal failure, chronic heart failure, and other clinical conditions.
      Increased ADMA levels are associated with reduced NO synthesis as assessed by
      impaired endothelium-dependent vasodilation or reduced NO metabolite levels. In
      several prospective and cross-sectional studies, ADMA has evolved as a marker of
      cardiovascular risk. Moreover, prospective clinical studies have suggested that
      it may play a role as a novel cardiovascular risk factor. Zoccali and coworkers
      were the first to show that elevated ADMA is associated with a three-fold
      increased risk of future severe cardiovascular events and mortality in patients
      undergoing hemodialysis. Valkonen and coworkers demonstrated in a nested case
      control study that elevated ADMA was associated with a four-fold increased risk
      for acute coronary events in clinically healthy, nonsmoking men. In patients with
      stable angina pectoris, preinterventional ADMA indicates the risk of developing
      restenosis or severe clinical events after coronary intervention. Furthermore, in
      humans with no underlying cardiovascular disease who are undergoing intensive
      care unit treatment, ADMA is a marker of the mortality risk. A number of
      additional prospective clinical trials are currently under way in diverse patient
      populations, among them individuals with congestive heart failure, cardiac
      transplantation patients, and patients with pulmonary hypertension. In summary,
      an increasing number of prospective clinical trials have shown that the
      association between elevated ADMA levels and major cardiovascular events and
      total mortality is robust and extends to diverse patient populations. However, we
      need to define more clearly in the future who will profit from ADMA
      determination, in order to use this novel risk marker as a more specific
      diagnostic tool.

PMID- 16444866
TI  - ADMA and hyperhomocysteinemia.
AB  - Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Like
      many other cardiovascular risk factors, hyperhomocysteinemia produces endothelial
      dysfunction due to impaired bioavailability of endothelium-derived nitric oxide
      (NO). The molecular mechanisms responsible for decreased NO bioavailability in
      hyperhomocysteinemia are incompletely understood, but emerging evidence suggests
      that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase,
      may be a key mediator. Homocysteine is produced during the synthesis of ADMA and
      can alter ADMA metabolism by inhibiting dimethylarginine dimethylaminohydrolase
      (DDAH). Several animal and clinical studies have demonstrated a strong
      association between plasma total homocysteine, plasma ADMA, and endothelial
      dysfunction. These observations suggest a model in which elevation of ADMA may be
      a unifying mechanism for endothelial dysfunction during hyperhomocysteinemia. The
      recent development of transgenic mice with altered ADMA metabolism should provide
      further mechanistic insights into the role of ADMA in hyperhomocysteinemia.

PMID- 16444867
TI  - Insulin resistance: potential role of the endogenous nitric oxide synthase
      inhibitor ADMA.
AB  - The insulin resistance syndrome (IRS) is considered to be a new target of risk
      reduction therapy. The IRS is a cluster of closely associated and interdependent
      abnormalities and clinical outcomes that occur more commonly in insulin
      resistant/hyperinsulinemic individuals. This syndrome predisposes individuals to
      type 2 diabetes, cardiovascular diseases, essential hypertension, certain forms
      of cancer, polycystic ovary syndrome, nonalcoholic fatty liver disease, and sleep
      apnea. In patients at high risk for cardiovascular diseases, endothelial
      dysfunction is observed in morphologically intact vessels even before the onset
      of clinically manifest vascular disease. Indeed, there are several lines of
      evidence that indicate that endothelial function is compromised in situations
      where there is reduced sensitivity to endogenous insulin. It is well established
      that a decreased bioavailability of nitric oxide (NO) contributes to endothelial
      dysfunction. Furthermore, NO may modulate insulin sensitivity. Activation of NO
      synthase (NOS) augments blood flow to insulin-sensitive tissues (i.e. skeletal
      muscle, liver, adipose tissue), and its activity is impaired in insulin
      resistance. Inhibition of NOS reduces the microvascular delivery of nutrients and
      blunts insulin-stimulated glucose uptake in skeletal muscle. Furthermore,
      induction of hypertension by administration of the NOS inhibitor NG-monomethyl-L
      arginine is also associated with insulin resistance in rats. Increased levels of
      asymmetric dimethylarginine (ADMA) are associated with endothelial vasodilator
      dysfunction and increased risk of cardiovascular diseases. An intriguing
      relationship exists between insulin resistance and ADMA. Plasma levels of ADMA
      are positively correlated with insulin resistance in nondiabetic, normotensive
      people. New basic research insights that provide possible mechanisms underlying
      the development of insulin resistance in the setting of impaired NO
      bioavailability will be discussed.

PMID- 16444868
TI  - DDAH gene and cardiovascular risk.
AB  - The crucial role of nitric oxide (NO) for normal endothelial function is well
      known. In many conditions associated with increased risk of cardiovascular
      diseases such as hypercholesterolemia, hypertension, abdominal obesity, diabetes
      and smoking, NO biosynthesis is dysregulated, leading to endothelial dysfunction.
      The growing evidence from animal and human studies indicates that endogenous
      inhibitors of endothelial NO synthase such as asymmetric dimethylarginine (ADMA)
      and NG-monomethyl-L-arginine (L-NMMA) are associated with the endothelial
      dysfunction and potentially regulate NO synthase. The major route of elimination
      of ADMA is metabolism by the enzymes dimethylarginine dimethylaminohydrolase-1
      and -2 (DDAH). In our recent study 16 men with either low or high plasma ADMA
      concentrations were screened to identify DDAH polymorphisms that could
      potentially be associated with increased susceptibility to cardiovascular
      diseases. In that study a novel functional mutation of DDAH-1 was identified; the
      mutation carriers had a significantly elevated risk for cardiovascular disease
      and a tendency to develop hypertension. These results confirmed the clinical role
      of DDAH enzymes in ADMA metabolism. Furthermore, it is possible that more common
      variants of DDAH genes contribute more widely to increased cardiovascular risk.

PMID- 16444870
TI  - Spotlight on endothelial progenitor cell inhibitors: short review.
AB  - Endothelial progenitor cells (EPCs) are bone-marrow-derived cells that enter the
      systemic circulation to replace defective or injured mature endothelial cells.
      EPCs also contribute to neovascularization and limit the progression of
      atherosclerosis. Patients with reduced EPC levels or dysfunctional EPCs are at
      increased risk for coronary artery disease. Drug-mediated improvement of the
      mobilization, differentiation, function and homing of EPCs to sites of ischemia
      or injured endothelium may therefore be a promising novel therapeutic approach
      for various cardiovascular diseases. On the other hand, endogenous inhibitors of
      EPCs could also be valuable drug targets. The identification of EPC inhibitors
      and the development of novel drugs that can efficiently regulate production or
      elimination of these molecules may also be a promising approach for the future
      treatment of atherosclerosis. In the present review we summarize potential
      endogenous and exogenous inhibitors of EPCs, such as oxidized low-density
      lipoproteins, angiotensin II, glucose, cigarette smoke and others. Whenever
      possible, we also describe the underlying molecular events. Drug-induced
      mobilization and improvement of EPC function, as well as reduction of EPC
      inhibitors, is likely to enhance endothelial function and reduce atherosclerotic
      processes.

PMID- 16444869
TI  - Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA).
AB  - Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor
      asymmetric dimethylarginine (ADMA) are found in various clinical settings,
      including renal failure, coronary heart disease, hypertension, diabetes and pre
      eclampsia. In healthy people acute infusion of ADMA promotes vascular
      dysfunction, and in mice chronic infusion of ADMA promotes progression of
      atherosclerosis. Thus, ADMA may not only be a marker but also an active player in
      cardiovascular disease, which makes it a potential target for therapeutic
      interventions. This review provides a summary and critical discussion of the
      presently available data concerning the effects on plasma ADMA levels of
      cardiovascular drugs, hypoglycemic agents, hormone replacement therapy,
      antioxidants, and vitamin supplementation. We assess the evidence that the
      beneficial effects of drug therapies on vascular function can be attributed to
      modification of ADMA levels. To develop more specific ADMA-lowering therapies,
      mechanisms leading to elevation of plasma ADMA concentrations in cardiovascular
      disease need to be better understood. ADMA is formed endogenously by degradation
      of proteins containing arginine residues that have been methylated by S
      adenosylmethionine-dependent methyltransferases (PRMTs). There are two major
      routes of elimination: renal excretion and enzymatic degradation by the
      dimethylarginine dimethylaminohydrolases (DDAH-1 and -2). Oxidative stress
      causing upregulation of PRMT expression and/or attenuation of DDAH activity has
      been suggested as a mechanism and possible drug target in clinical conditions
      associated with elevation of ADMA. As impairment of DDAH activity or capacity is
      associated with substantial increases in plasma ADMA concentrations, DDAH is
      likely to emerge as a prime target for specific therapeutic interventions.

PMID- 16444871
TI  - Asymmetric dimethylarginine (ADMA) accelerates cell senescence.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide
      synthase and its accumulation has been associated with cardiovascular disease. We
      aimed to investigate the role of ADMA in endothelial cell senescence. Endothelial
      cells were cultured until the tenth passage. ADMA was replaced every 48 hours
      starting at the fourth passage. ADMA significantly accelerated senescence
      associated beta-galactosidase activity. Additionally, the shortening of telomere
      length was significantly speeded up and telomerase activity was significantly
      reduced. This effect was associated with an increase of oxidative stress: both
      allantoin, a marker of oxygen free radical generation, and intracellular reactive
      oxygen species increased significantly after ADMA treatment compared with
      control, whereas nitric oxide synthesis decreased. Furthermore, ADMA-increased
      oxidative stress was accompanied by a decrease in the activity of
      dimethylarginine dimethylaminohydrolase, the enzyme that degrades ADMA, which
      could be prevented by the antioxidant pyrrolidine dithiocarbamate. Exogenous ADMA
      also stimulated secretion of monocyte chemotactic protein-1 and interleukin-8. Co
      incubation with the methyltransferase inhibitor S-adenosylhomocysteine abolished
      the effects of ADMA. These data suggest that ADMA accelerates senescence,
      probably via increased oxygen radical formation by inhibiting nitric oxide
      elaboration. This study provides evidence that modest changes of intracellular
      ADMA levels are associated with significant effects on slowing down endothelial
      senescence.

PMID- 16444872
TI  - ADMA metabolism and clearance.
AB  - The plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous
      inhibitor of nitric oxide synthase, is the resultant of many processes at
      cellular and organ levels. Post-translational methylation of arginine residues of
      proteins plays a crucial role in the regulation of their functions, which include
      processes such as transcription, translation and RNA splicing. Because protein
      methylation is irreversible, the methylation signal can be turned off only by
      proteolysis of the entire protein. Consequently, most methylated proteins have
      high turnover rates. Free ADMA, which is formed during proteolysis, is actively
      degraded by the intracellular enzyme dimethylarginine dimethylaminohydrolase
      (DDAH). Some ADMA escapes degradation and leaves the cell via cationic amino acid
      transporters. These transporters also mediate uptake of ADMA by neighboring cells
      or distant organs, thereby facilitating active interorgan transport. Clearance of
      ADMA from the plasma occurs in small part by urinary excretion, but the bulk of
      ADMA is degraded by intracellular DDAH, after uptake from the circulation. This
      review discusses the various processes involved in ADMA metabolism: protein
      methylation, proteolysis of methylated proteins, metabolism by DDAH, and
      interorgan transport. In addition, the role of the kidney and the liver in the
      clearance of ADMA is highlighted.

PMID- 16444873
TI  - Arginine metabolism in vascular biology and disease.
AB  - Arginine metabolism plays a major role in cardiovascular physiology and
      pathophysiology, largely via nitric oxide (NO)-dependent processes. It is
      becoming increasingly apparent, however, that arginine metabolic enzymes other
      than the NO synthases can also play important roles via both NO-dependent and 
      independent processes. There are three sources of arginine in vivo and at least
      five mammalian enzymes or enzyme families that utilize arginine as substrate.
      Changes in arginine availability or in production of the different end products
      of the various arginine metabolic pathways can have distinct and profound
      physiologic consequences. However, our knowledge regarding the complex interplay
      between these pathways at the level of the whole body, specific tissues, and even
      individual cells, is incomplete. This review will highlight recent findings in
      this area that may suggest additional avenues of investigation that will allow a
      fuller understanding of cardiovascular physiology in health and disease.

PMID- 16444874
TI  - Quantification of ADMA: analytical approaches.
AB  - Methylated L-arginine analogs are involved in nitric oxide synthase activity
      regulation. Methods based on high-performance liquid chromatography with
      fluorescence, capillary electrophoresis, or ion exchange chromatography with
      absorbance detection were first applied for the quantitative determination of N
      monomethyl-L-arginine (NMMA), asymmetric dimethylarginine (ADMA) and symmetric
      dimethylarginine (SDMA) in human blood and urine. These assays revealed elevated
      circulating levels of ADMA in various diseases and gave accumulating evidence of
      the usefulness of ADMA as a cardiovascular risk factor. However, the methods used
      are hampered by the fact that NMMA, ADMA and SDMA can be distinguished from L
      arginine only by means of chromatographic separation. This has promoted the
      development of alternatives that involve mass spectrometry (MS) technology.
      Today, various MS-based approaches such as liquid chromatography (LC)-MS, LC
      MS/MS, gas chromatography (GC)-MS, and GC-MS/MS are available. L-arginine and its
      analogs have been subjected to LC-MS analysis with and without further
      derivatization to their o-phthaldialdehyde derivatives. For these methods,
      labelled L-arginine was used as the internal standard. The first MS-based method
      that distinguishes NMMA, ADMA, SDMA and L-arginine by mass-to-charge (m/z)-ratio
      has been reported by Tsikas et al. This GC-MS approach has been further improved
      by Albsmeier et al by introducing labelled ADMA as an internal standard. As an
      alternative to existing methods, a commercially available ELISA kit has recently
      been developed and validated.

PMID- 16444876
TI  - Institute's vital role stressed.
AB  - IHEEM is emphasising the importance of its activities that support the design,
      construction, maintenance and operation of healthcare buildings. This article
      conveys messages that the Institute is delivering to Government and senior
      executives in the health sector.

PMID- 16444875
TI  - ADMA and oxidative stress may relate to the progression of renal disease:
      rationale and design of the VIVALDI study.
AB  - The renin angiotensin system has been shown to be involved in the pathogenesis of
      vascular and renal sequelae of diabetes mellitus. In type 2 diabetes mellitus,
      angiotensin receptor blockers have been shown to exert clinical benefit by
      reducing the progression of diabetic nephropathy. They also improve endothelium
      mediated vascular function. The latter effect is partly due to the reduction of
      angiotensin II-associated oxidative stress. Moreover, small clinical studies have
      shown that treatment with angiotensin receptor blockers also reduces the
      circulating levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor
      of nitric oxide (NO) synthase. In the VIVALDI trial, the ability of the
      angiotensin receptor blocker telmisartan to reduce the progression of diabetic
      nephropathy (associated with proteinuria) in comparison with valsartan in more
      than 800 patients with type 2 diabetes during 1 year of treatment is being
      studied. In order to gain more detailed insight into the potential
      pathomechanisms associated with this effect, further end-points have been
      defined. Among these are the circulating levels of ADMA and the urinary excretion
      rate of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha). The former is an
      endogenous inhibitor of NO-mediated vascular function(s) and a prospectively
      determined marker of major cardiovascular events and mortality; the latter is a
      lipid peroxidation product resulting from the nonenzymatic peroxidation of
      arachidonic acid, which exerts detrimental vascular effects similar to those of
      thromboxane A2. Urinary 8-iso-PGF2alpha has been shown in clinical studies to be
      an independent marker of cardiovascular disease. Highlighting the effects of
      telmisartan on ADMA and 8-iso-PGF levels in such a large cohort of diabetic
      patients will enhance our understanding of the roles of dysfunctional NO
      metabolism and redox mechanisms in the pathogenesis of end-organ damage and its
      prevention by pharmacotherapy with angiotensin receptor blockers.

PMID- 16444877
TI  - Striving to be 'envy of the world'.
AB  - IHEEM's Healthcare Estates Conference, held at Harrogate in November 2005,
      clearly underlined how architects, designers, constructors, engineers, and estate
      and facility managers need to work cohesively to ensure healthcare premises are
      fully safe and fit for function - both now and in the long term. Nicholas
      Marshall and Jason Rayfield report.

PMID- 16444879
TI  - NHS core principles must be protected.
AB  - Jason Rayfield explores the implications of the increasing use of private sector
      funding, risk management, competition principles and expertise for NHS healthcare
      delivery.

PMID- 16444878
TI  - EMF issues must be fully managed.
AB  - Commanding increased attention are issues relating to electromagnetic fields
      (EMFs) in the workplace and a new EC Directive. Technical report by Dr Didier
      Bozec DUT (France) BSc (Hons) PhD MIEE MIEEE MIHEEM, laboratory manager, York EMC
      Services; and Dr Mark Tyndall MPhys (Hons) PhD, engineer, York EMC Services.

PMID- 16444880
TI  - Reflecting on theatre explosion danger.
AB  - Risk of explosion and fire in operating theatres used to be significant. For this
      Health Estate Journal 'Then and now' feature, Mike Arrowsmith BSc (Hons) CEng
      FIMechE FIHEEM, technical editor, provides commentary on an article which was
      published in December 1945 in the second issue of The Hospital Engineer, a
      publication then taking the form of a newsletter--of The Institution of Hospital
      Engineers. The 1945 article was formed from a short paper read at an Institution
      branch meeting, and a slightly amended version of the article text follows the
      commentary.

PMID- 16444881
TI  - P21 lays foundations for improvement.
AB  - By fostering teamwork and promoting transparent and efficient ways of working,
      the ProCure2l scheme is helping to change the healthcare environment for the
      better, according to Mike Douglas, director and chairman and Amrit Naru,
      healthcare team leader, Netts Architects.

PMID- 16444882
TI  - Creativity essential in lighting design.
AB  - Laura Bayliss, lighting designer with BDP Lighting, questions the quantitative
      approach to lighting for healthcare - and makes the case for creative lighting
      design. This article was originally published in the Institution of Lighting
      Engineers' The Lighting Journal in summer 2005, after winning the ILE-sponsored
      "Best Written Paper" in the 2005 Young Lighters Awards.

PMID- 16444883
TI  - On track.

PMID- 16444885
TI  - Mobilizing materials management.

PMID- 16444884
TI  - Progress on a work in progress.

PMID- 16444886
TI  - Out with the old, in with the new.

PMID- 16444887
TI  - Shred City.

PMID- 16444888
TI  - Predictive analytics and the new world of retail healthcare.

PMID- 16444889
TI  - Making the first call count.

PMID- 16444890
TI  - Identity and access management: the starting point for a RHIO.

PMID- 16444891
TI  - Neonatal outcomes with different betamethasone dosing regimens: a comparison.
AB  - OBJECTIVE: To determine any differences in neonatal outcomes when dosing
      betamethasone every 12 hours vs. 24 hoursfor anticipated preterm delivery. STUDY
      DESIGN: A retrospective review of births at <36 weeks' gestation from January 1,
      1996, to July 1, January 1, 1996, to July 1, 2000. Maternal and neonatal charts
      were reviewed. The deliveries were separated into 3 groups: those not receiving
      antenatal corticosteroids, those who received betamethasone 12 hours apart and
      those who received 24-hour dosing. Demographic, obstetric and neonatal variables
      were compared between the groups. RESULTS: There were 909 deliveries analyzed.
      With the 2 betamethasone groups, a significant difference was found for more
      maternal antibiotic use (90.4% vs. 83.6%, p=0.03), venous cord blood gas pH (7.31
      vs. 7.32, p=0.04) and neonatal surfactant use (39.8% vs. 25.5%, p = 0.001) in the
      12-hour group as compared to the 24-hour group. For all other outcomes there was
      no difference. CONCLUSION: Outcomes using a 12-hour dosing schedule of
      betamethasone were similar to those using a 24-hour regimen in this retrospective
      review. Twelvehour dosing could be considered an alternative way to deliver
      antenatal corticosteroids.

PMID- 16444892
TI  - Excessive uterine contractions: effect on the incidence of preterm delivery in
      twin gestation.
AB  - OBJECTIVE: To evaluate the effect of uterine contractions on the incidence of
      preterm delivery within 7 and 14 days in twin pregnancies. STUDY DESIGN: Study
      patients were identified from a large database composed of women receiving
      outpatient surveillance with home uterine contraction monitoring. We included
      tracings collected on a routine or acute basis from twin pregnancies without
      cerclage at 24.0-36.0 weeks. Tracings from patients with indicated delivery were
      excluded. Fisher's exact and Pearson's X2 tests were used. RESULTS: Datafrom
      2,423 patients who recorded 8,291 acute tracings and 12,649 routine tracings were
      analyzed. Preterm delivery within 7 days followed 1.4% of routine vs. 6.6% of
      acute tracings (p < 0.001). Preterm delivery within 14 days followed 5.1% of
      routine vs. 16.8% of acute tracings (p < 0.001). CONCLUSION: Preterm uterine
      contractions affect pregnancy prolongation and outcome in twin pregnancies
      utilizing outpatient surveillance. Evaluation of patients exhibiting elevated
      preterm uterine contractions is warranted.

PMID- 16444894
TI  - Mastalgia: a review of management.
AB  - Mastalgia affects up to two-thirds of women at some time during their
      reproductive lives. It is usually benign, but thefear of underlying breast cancer
      is why many women present for evaluation. Mastalgia can be associated with
      premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and,
      rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie
      syndrome, present as mastalgia. A thorough clinical evaluation is required to
      assess the cause. The majority of women can be reassured after a clinical
      evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast
      support; a low-fat, high-carbohydrate diet; and topical nonsteroidal
      antiinflammatory agents are reasonable first-line treatments. Hormonal agents,
      such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in
      the treatment of mastalgia. Side effects, however, limit their extensive use.
      Danazol is the only FDA-approved hormonal treatment and is best used in cyclic
      form to limit the adverse effects. Lisuride maleate is a new agent recently
      studied for the treatment of mastalgia. Initial data on this medication are
      encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic
      mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of
      cases.

PMID- 16444893
TI  - Diagnostic imaging in uterine incisional necrosis/dehiscence complicating
      cesarean section.
AB  - OBJECTIVE: To review the diagnostic imaging studies in patients with surgically
      proven uterine incisional necrosis/dehiscence complicating cesarean section and
      to compare these studies with the findings at surgery. STUDY DESIGN: Over a 6
      year period, the records of 7 patients with imaging studies prior to surgery for
      uterine incisional necrosis/dehiscence complicating cesarean delivery were
      reviewed and compared with the findings at surgery. RESULTS: Four cases underwent
      computed tomography (CT) and sonography, 1 underwent CT only, and 2 underwent
      sonography only. Abnormal findings included abdominal free fluid in 4, pleural
      effusions in 3, dilated bowel in 3, possible bladder flap hematoma in 2 and
      single instances of liver abscess and retained products of conception. In no
      cases were all the studies normal, and necrosis/dehiscence was not demonstrated
      in any patient. CONCLUSION: Abdominal free fluid, bowel distension, pleural
      effusion and bladder flap hematoma seen on CT or sonogram in the postcesarean
      context suggest the possibility of uterine incisional necrosis/dehiscence.
      Magnetic resonance imaging (MRI) might then be indicated since MRI may be
      superior to CT in evaluating complications at the incisional site because of its
      multiplanar capability and greater degree of soft tissue contrast.

PMID- 16444895
TI  - Risk of bladder injury during vaginal hysterectomy in women with a previous
      cesarean section.
AB  - OBJECTIVE: To determine the risk of bladder injury during vaginal hysterectomy in
      women with a previous cesarean section. STUDY DESIGN: Analysis of selected
      studies found through a MEDLINE search from 1980 to 2003. RESULTS: Four
      comparative studies (women with or without a previous cesarean section) were
      selected and analyzed. Risk of bladder injury was significantly increased in only
      1 study. Analysis of cumulative data did not find a significant difference (8 of
      430 [1.86%] vs. 11 of 1,227 [0.89%], p = 0.12). CONCLUSION: The risk of bladder
      injury during vaginal hysterectomy does not seem to be increased in women with a
      previous cesarean section.

PMID- 16444896
TI  - Oral ovulation induction agents combined with low-dose gonadotropin injections
      and intrauterine insemination: cost- and clinical effectiveness.
AB  - OBJECTIVE: To compare the efficacy and cost-effectiveness of different induction
      protocols involving gonadotropins with intrauterine insemination (IUI). STUDY
      DESIGN: We performed a retrospective chart review of 648 IUI cycles. Some
      patients had gonadotropin injections alone before human chorionic gonadotropin
      (hCG) and IUI (human menopausal gonadotropin protocol); others were given oral
      medications, then gonadotropins before hCG and IUI (combination protocol).
      Outcomes included pregnancy rates, multiple birth rates, endometrial thickness,
      number of ovarian follicles, injection days, ampules of gonadotropins and cost.
      RESULTS: The combination protocol was more cost-effective. In first cycles,
      pregnancy rates, multiple birth rates, number of large follicles produced and
      cancellation rates were similar. The combination group had fewer days of
      injections and fewer ampules used. When all cycles were analyzed, the multiple
      birth rate was lower in the combination group. Comparing the different oral
      medications in the combination protocols, letrozole yielded higher pregnancy
      rates than tamoxifen or clomiphene. Multiple birth rates were similar for all
      oral medications. CONCLUSION: Combination protocols are less costly and equally
      effective, with potentially fewer multiple births than with gonadotropins alone.
      Letrozole may be more effective than clomiphene and tamoxifen in a combination
      protocol.

PMID- 16444897
TI  - Maternal mortality in the U.S. Department of Defense, 1993-1998.
AB  - OBJECTIVE: To determine the maternal mortality ratio (MMR) in Department of
      Defense medical facilities from 1993 to 1998. STUDY DESIGN: We conducted a
      retrospective review of birth data from military medical facilities using the
      Standard Inpatient Data Records from 1993 through 1998. The total number of live
      births and dispositions due to maternal death were obtained. RESULTS: Twenty-two
      maternal deaths occurred in the study time out of 398,107 live births, for an MMR
      of 5.5 per 100,000 live births. The ratiosfor the service branches were: Army
      7.0, Navy 5.3 and Air Force 3.6. The leading cause of death was embolic disease.
      CONCLUSION: The military MMR is closer to the Healthy People 2010 goal of 3.3
      than is the national ratio, 13.2. Improved reporting of cases, patient education
      and treating high-risk conditions may help further decrease pregnancy-related
      mortality.

PMID- 16444898
TI  - Intractable hiccups as an unusual presentation of a uterine leiomyoma: a case
      report.
AB  - BACKGROUND: Hiccups, or singultus, are an abrupt, intense contraction of the
      inspiratory muscles accompanied by closure of the glottis and are experienced by
      most people. people. CASE: A 41-year-old woman with a large uterine myoma
      presented with recurrent and intractable hiccup boutsfor 1 year. The hiccups
      resolved spontaneously after hysterectomy. CONCLUSION: A uterine leiomyoma,
      especially the subserosal type, might become a possible etiology of hiccups when
      large enough to cause irritation of the vagus or phrenic nerve.

PMID- 16444899
TI  - Interaction between emotion and memory: importance of mammillary bodies damage in
      a mouse model of the alcoholic Korsakoff syndrome.
AB  - Chronic alcohol consumption (CAC) can lead to the Korsakoff syndrome (KS), a
      memory deficiency attributed to diencephalic damage and/or to medial temporal or
      cortical related dysfunction. The etiology of KS remains unclear. Most animal
      models of KS involve thiamine-deficient diets associated with pyrithiamine
      treatment. Here we present a mouse model of CAC-induced KS. We demonstrate that
      CAC-generated retrieval memory deficits in working/ episodic memory tasks,
      together with a reduction of fear reactivity, result from damage to the
      mammillary bodies (MB). Experimental lesions of MB in non-alcoholic mice produced
      the same memory and emotional impairments. Drugs having anxiogenic-like
      properties counteract such impairments produced by CAC or by MB lesions. We
      suggest (a) that MB are the essential components of a brain network underlying
      emotional processes, which would be critically important in the retrieval
      processes involved in working/ episodic memory tasks, and (b) that failure to
      maintain emotional arousal due to MB damage can be a main factor of CAC-induced
      memory deficits. Overall, our animal model fits well with general
      neuropsychological and anatomic impairments observed in KS.

PMID- 16444900
TI  - Memory effects of benzodiazepines: memory stages and types versus binding-site
      subtypes.
AB  - Benzodiazepines are well established as inhibitory modulators of memory
      processing. This effect is especially prominent when applied before the
      acquisition phase of a memory task. This minireview concentrates on the putative
      subtype selectivity of the acquisition-impairing action of benzodiazepines.
      Namely, recent genetic studies and standard behavioral tests employing subtype
      selective ligands pointed to the predominant involvement of two subtypes of
      benzodiazepine binding sites in memory modulation. Explicit memory learning seems
      to be affected through the GABAA receptors containing the alpha1 and alpha5
      subunits, whereas the effects on procedural memory can be mainly mediated by the
      alpha1 subunit. The pervading involvement of the alpha1 subunit in memory
      modulation is not at all unexpected because this subunit is the major subtype,
      present in 60% of all GABAA receptors. On the other hand, the role of alpha5
      subunits, mainly expressed in the hippocampus, in modulating distinct forms of
      memory gives promise of selective pharmacological coping with certain memory
      deficit states.

PMID- 16444901
TI  - Genetic mouse models of Alzheimer's disease.
AB  - In the current minireview, we focus on genetic mouse models of Alzheimer's
      disease (AD). Because various excellent, up-to-date reviews, special issues, and
      reliable websites are already dedicated to the genetics of Alzheimer's disease in
      general and of animal models in particular, this review is not meant to be
      comprehensive. Rather, we aim to steer the Alzheimer's novice through the recent
      mouse literature on AD. Special attention will be paid to genetic models that
      have been tested behaviorally.

PMID- 16444902
TI  - The role of insulin, insulin growth factor, and insulin-degrading enzyme in brain
      aging and Alzheimer's disease.
AB  - Most brain insulin comes from the pancreas and is taken up by the brain by what
      appears to be a receptor-based carrier. Type 2 diabetes animal models associated
      with insulin resistance show reduced insulin brain uptake and content. Recent
      data point to changes in the insulin receptor cascade in obesity-related insulin
      resistance, suggesting that brain insulin receptors also become less sensitive to
      insulin, which could reduce synaptic plasticity. Insulin transport to the brain
      is reduced in aging and in some animal models of type 2 diabetes; brain insulin
      resistance may be present as well. Studies examining the effect of the
      hyperinsulinic clamp or intranasal insulin on cognitive function have found a
      small but consistent improvement in memory and changes in brain neuroelectric
      parameters in evoked brain potentials consistent with improved attention or
      memory processing. These effects appear to be due to raised brain insulin levels.
      Peripheral levels of Insulin Growth Factor-1 (IGF-I) are associated with glucose
      regulation and influence glucose disposal. There is some indication that reduced
      sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and
      diabetes, decreases the clearance of Abeta amyloid. Such a decrease involves the
      insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF
      I may modulate brain levels of insulin degrading enzyme, which would also lead to
      an accumulation of Abeta amyloid.

PMID- 16444903
TI  - Erythropoietin improves place learning in an 8-arm radial maze in fimbria-fornix
      transected rats.
AB  - Systemically administered human recombinant erythropoietin (EPO) may have the
      potential to reduce the cognitive and behavioral symptoms of mechanical brain
      injury. In a series of studies, we address this possibility. We previously found
      that EPO given to fimbria-fornix transected rats at the moment of injury could
      substantially improve the posttraumatic acquisition of an allocentric place
      learning task when such a task is administered in a water maze. Due to the
      clinical importance of such results, it is important to scrutinize whether the
      therapeutic effect of EPO is specific to the experimental setup of our original
      experiments or generalizes across test situations. Consequently, here we studied
      the effects of similarly administered EPO in fimbria-fornix transected and
      control operated rats, respectively, evaluating the posttraumatic
      behavioral/cognitive abilities in an allocentric place learning task administered
      in an 8-arm radial maze. The administration of EPO to the hippocampally injured
      rats was associated with a virtually complete elimination of the otherwise severe
      behavioral impairment caused by fimbria-fornix transection. In contrast, EPO had
      no detectable effect on the task acquisition of non-lesioned animals. The results
      of the present study confirm our previous demonstration of EPO's ability to
      reduce or eliminate the behavioral/cognitive consequences of mechanical injury to
      the hippocampus, while adding the important observation that such a therapeutic
      effect is not restricted to the specific experimental setup previously studied.

PMID- 16444904
TI  - Response to novelty correlates with learning rate in a Go/No-go task in Gottingen
      minipigs.
AB  - Novelty-seeking and harm-avoidance personality traits influence Go/No-go (GNG)
      learning in humans. Animal studies have also indicated a link between response to
      novelty and spatial discrimination learning. In the present study, we test the
      hypothesis that learning rate in a GNG task correlates with the behavioral
      response of Gottingen minipigs to novelty. In a group of 12 minipigs of mixed
      genders, response to novelty was measured by numbers of contacts with a novel
      object, and the total duration of exploration of the novel object. These
      parameters were correlated to individual learning rate in a GNG task. The number
      of sessions to reach criterion in the GNG task correlated significantly with the
      number of contacts to a novel object (r = 0.70, p = 0.03), but not with the
      duration of object exploration (r = 0.29, p = 0.41). Thus, pigs with a low
      behavioral response to novelty learned the GNG task faster than did pigs with a
      strong behavioral response to novelty, indicated by the tendency to approach
      novel objects. We hypothesize that the critical factor in this relation is
      difference in emotional reactivity rather than difference in motivation for
      exploration. In conclusion, in addition to 'cognitive' ability, 'temperamental'
      factors are likely to influence learning in individual pigs.

PMID- 16444905
TI  - Twice-daily dosing of loracarbef 15 mg/kg versus 30 mg/kg in the treatment of
      children with acute sinusitis.
AB  - Loracarbef is an oral synthetic beta-lactam antibiotic of the carbacephem class.
      The aim of this study was to compare the efficacy and safety of loracarbef 15
      mg/kg versus 30 mg/kg in children with acute sinusitis. A randomized, parallel
      group, clinical study was conducted. Fifty-eight children aged 5-12 years with
      acute sinusitis were divided into two groups, which received either loracarbef 15
      mg/kg/day or 30 mg/kg/day orally, divided in two doses for 10 days. Clinical
      examination, anterior rhinoscopy and sinus radiographs were performed at the
      beginning of treatment. Clinical evaluation was repeated in a second session, 0-2
      days after the final dose, and in a third session, 30 days after the beginning of
      the treatment. Sinus X-rays were repeated selectively in the second session and
      in all patients in the third session. Nineteen of 29 (65.5%) patients in the 15
      mg/kg/day group and 26 of 29 (89.6%) in the 30 mg/kg/day group were characterized
      as completely or clinically cured at the end of the study. In conclusion, a
      statistically significant difference between the two treatment groups was shown
      with better results in the 30 mg/kg group. Despite the slight difference in
      adverse events between the two groups (with fewer adverse events in the 15 mg/kg
      group), we recommend that if loracarbef is chosen as initial therapy in acute
      sinusitis, a regimen of 30 mg/kg/day in two doses is followed.

PMID- 16444906
TI  - Improvement of otitis media with effusion after treatment of asthma with
      leukotriene antagonists in children with co-existing disease.
AB  - Otitis media with effusion (OME) is a common pediatric disease and there is great
      controversy concerning its management. Mechanical, medical and surgical
      treatments have not proven adequate in resolving the disease and serve mainly to
      manage complications. Leukotriene inhibitors are new drugs that have been
      approved recently for the treatment of asthma in children. The aim of this study
      was to evaluate the impact of leukotriene inhibitor therapy for asthma on the
      clinical course of OME in children with co-existing disease. Fifty children with
      bilateral OME and asthma, divided equally into two groups, were studied. The
      children in the first group were treated with budesonide and terbutaline inhalers
      together with the leukotriene inhibitor montelukast, whereas the children in the
      second group were treated with the inhalers alone. Duration of treatment was 30
      days. Pneumatic otoscopy, tympanometry and pure-tone audiometry were performed at
      the beginning and at the end of treatment. Fifteen (60%) of the children
      receiving inhalers and montelukast and nine (36%) of those receiving only
      inhalers were found free of OME after 30 days of therapy. Thus, it may be
      concluded that a statistically significant beneficial effect on the clinical
      course of OME resulted from the addition of montelukast to the treatment of
      children with co-existing asthma and OME. Given that no medication has been shown
      to be effective in OME therapy, further investigation of the possible effects of
      leukotriene inhibitors is warranted.

PMID- 16444907
TI  - Is itraconazole the treatment of choice in Microsporum canis tinea capitis?
AB  - Mycotic scalp infection caused by Microsporum canis is the most dominant cause of
      tinea capitis in Greece. Griseofulvin has been the gold standard for the
      treatment of tinea capitis, but it is unavailable in our country. In this study,
      we evaluated 111 children with M. canis tinea capitis that were treated with
      itraconazole. Eighty-one of them were treated with itraconazole capsule pulse
      therapy (group A) and 30 (group B) were treated with oral suspension administered
      in continuous regimen. Twenty-one patients, all from group A, were lost to follow
      up, probably due to the length of this regimen. In all patients that made up the
      study protocol, complete cure was achieved within seven pulses for group A and 12
      weeks for group B. No significant side effects to lead to the cessation of
      therapy were recorded. Laboratory investigations were performed in 32 randomly
      chosen patients and were within normal ranges. The response to therapy did not
      appear to depend upon the formulation administered (capsules versus suspension).
      Using the pulse regimen, we also believe that it is necessary to individualize
      the number of pulses administered according to the clinical response. In
      conclusion, itraconazole proved safe and effective in our study, providing an
      ideal alternative to griseofulvin.

PMID- 16444908
TI  - Objective biophysical findings in patients with sensitive skin.
AB  - The term sensitive skin has been used to describe a clinical phenomenon of
      hyperreactivity of the human skin, which develops exaggerated reactions when
      exposed to external factors. The aim of this study was to determine objective
      biophysical findings in patients with sensitive skin compared to those
      individuals with nonsensitive skin. Thirty-two patients with sensitive skin and
      30 healthy volunteers with nonsensitive skin were studied. The testing methods
      included in vivo and in vitro tests: epicutaneous testing (Patch tests);
      measurement of sebum and hydration of the skin; alkali resistance test; stinging
      test with lactic acid; reaction to aqueous solution of methyl nicotinate 0.5%,
      1.4% and acetyl-b-methylcholine chloride 1:1000; pH measurement; dermographism;
      and measurement of total and specific IgE. Significant results were observed in
      the measurement of sebum (p < 0.01) and hydration (p < 0.05) of the skin, in the
      alkali resistance test (p < 0.05), in the vascular reaction to methyl nicotinate
      (p < 0.01) and to acetyl-b-methylcholine chloride (p < 0.01) and in the skin
      response to allergens of the European standard (p < 0.01) and cosmetic series (p
      < 0.05). In addition, the subjective findings of stinging test produced
      significant results (p < 0.001) as was anticipated. Patients with sensitive skin
      possess very dry skin with low fatness, which leads to a disturbance of the
      protective skin barrier function. They also present a hyperreaction of the skin
      blood vessels, increased transcutaneous penetration of water-soluble chemicals,
      enhanced immune responsiveness, significant decrease of alkali resistance and a
      heightened neurosensory stimulation.

PMID- 16444909
TI  - Psychiatric factors in patients with sensitive skin.
AB  - The term sensitive skin has been used to describe a clinical phenomenon of skin
      hyperreactivity induced after exposure to different external factors. The
      diagnosis is mainly based on patient's self-assessment because of the lack of
      objective clinical signs of the disease. The aim of this study was to investigate
      psychiatric factors in patients with sensitive skin and to estimate the possible
      need for psychological intervention to these patients. Thirty-seven patients with
      sensitive skin and 38 individuals with nonsensitive skin were studied. The
      psychometric instruments used were the Symptom Checklist-90 (SCL-90) and the
      Delusions-Symptoms-States Inventory/states of Anxiety and Depression (DSSI/sAD).
      Statistically significant differences in subjects with sensitive skin compared to
      those with nonsensitive skin were observed in the SCL-90 subscales of
      somatization, phobic anxiety, hostility, interpersonal sensitivity and the
      DSSI/sAD subscale of anxiety. Our findings suggest that somatization, anxiety,
      phobic anxiety, hostility and interpersonal sensitivity symptoms may be
      associated with hypersensitivity of human skin. Psychological factors should be
      taken into consideration in the treatment of patients with sensitive skin.

PMID- 16444910
TI  - A comparison of the effects of D-003 and policosanol (5 and 10 mg/day) in
      patients with type II hypercholesterolemia: a randomized, double-blinded study.
AB  - The main goal of hypercholesterolemia management for coronary prevention is to
      reduce serum low-density lipoprotein cholesterol (LDL-C) levels. D-003 is a
      mixture of high molecular weight aliphatic acids purified from sugarcane wax,
      while policosanol is a cholesterol-lowering drug purified from the same source,
      consisting in a mixture of higher aliphatic alcohols. No previous comparative
      study of both drugs in humans has been reported. This randomized, double-blind
      study compares the efficacy and tolerability of D-003 and policosanol (5 and 10
      mg/day) in patients with type II hypercholesterolemia. After a baseline period,
      100 patients were randomized to D-003 or policosanol both at 5 mg/day and 10
      mg/day, for 8 weeks. D-003 and policosanol 5 mg/day reduced (p < 0.0001) LDL-C by
      26.9% and 20.9%, respectively. These reductions increased with 10 mg/day (35.1%
      for D-003, 25.1% for policosanol. The reductions of LDL-C achieved with D-003 5
      mg/day and 10 mg/day were greater (p < 0.05 and p < 0.001, respectively) than
      with policosanol. The frequency of patients treated with D-003 (5 mg/day)
      reaching LDL-C reductions > or = 15% (22/25, 88%) was greater (p < 0.01) than
      with policosanol (5 mg/day) (19/25, 76%), and the same was true for D-003 10
      mg/day (25/25, 100%) and policosanol (22/25, 88%; p < 0.01). D-003 and
      policosanol (5 mg/day) also lowered (p < 0.001) total cholesterol (TC) (16.2% and
      13.5%, respectively), and increased high-density lipoprotein cholesterol (HDL-C)
      by 15.3% (D-003) and 6.7% (policosanol). At 10 mg/day, D-003 and policosanol
      reduced (p < 0.001) TC (21.3% and 16.0%, respectively), while HDL-C was increased
      by 17.3% and 9.8%, respectively, D-003 being more effective than policosanol.
      Treatments did not affect triglycerides. Both drugs were well tolerated, with D
      003 tolerated as well as policosanol. Three patients discontinued the study, none
      due to adverse events (AEs). Seven patients (three from the D-003 group and four
      from the policosanol group) experienced mild AEs. In conclusion, D-003 (5 and 10
      mg/day) administered to patients with type II hypercholesterolemia was more
      effective than policosanol in lowering LDL-C and TC, and in increasing HDL-C. D
      003 could be useful for treating type II hypercholesterolemia, but this subject
      deserves further clinical research.

PMID- 16444911
TI  - Abdominal aortic aneurysms: what we don't seek we won't find.

PMID- 16444912
TI  - Should we screen for abdominal aortic aneurysms?
AB  - Ultrasonography can screen for abdominal aortic aneurysms (AAAs) safely, cheaply,
      and accurately. Once detected, an AAA can be monitored and repaired before it is
      likely to rupture. The US Preventive Services Task Force recently recommended a
      one-time screening for AAAs by ultrasonography for men age 65 to 75 years who
      have ever smoked. We should consider expanding the recommendations to include
      others at risk.

PMID- 16444913
TI  - What is osteopenia, and what should be done about it?

PMID- 16444914
TI  - In rebuttal: Osteopenia is a useful diagnosis.

PMID- 16444915
TI  - How should we advise patients about the contraceptive patch, given the FDA
      warning?

PMID- 16444916
TI  - The clinical picture. Severe chest pain in a 32-year-old man.

PMID- 16444917
TI  - Familial hypercholesterolemia: a challenge of diagnosis and therapy.
AB  - People with familial hypercholesterolemia (FH) have dramatically high levels of
      low-density lipoprotein cholesterol (LDL-C), which can lead to accelerated
      atherosclerosis and, if untreated, early cardiovascular death. Although the
      heterozygous form of FH is often unrecognized, detecting it early can enable risk
      reduction before premature coronary heart disease occurs.

PMID- 16444918
TI  - Diabetes insipidus: diagnosis and treatment of a complex disease.
AB  - Diabetes insipidus, characterized by excretion of copious volumes of dilute
      urine, can be life-threatening if not properly diagnosed and managed. It can be
      caused by two fundamentally different defects: inadequate or impaired secretion
      of antidiuretic hormone (ADH) from the posterior pituitary gland (neurogenic or
      central diabetes insipidus) or impaired or insufficient renal response to ADH
      (nephrogenic diabetes insipidus). The distinction is essential for effective
      treatment.

PMID- 16444919
TI  - Contrast-induced nephropathy: how it develops, how to prevent it.
AB  - No current treatment can reverse or ameliorate contrast-induced nephropathy once
      it occurs, but prophylaxis is possible. Many preventive measures have failed to
      show benefits in well-designed, prospective, randomized, double-blinded trials.
      This review will focus only on the prophylactic strategies that have possible or
      proven value.

PMID- 16444920
TI  - Multiple sclerosis: advances in understanding, diagnosing, and treating the
      underlying disease.
AB  - Recent advances in our understanding of the diagnosis, imaging, pathology, and
      clinical monitoring of multiple sclerosis (MS) have significantly increased our
      ability to successfully treat this often perplexing neurologic disorder. Magnetic
      resonance imaging (MRI) is now integral to the diagnostic process. Treatment of
      MS can be considered as three parallel pathways: treatment of relapses, symptom
      management, and long-term prevention of tissue injury.

PMID- 16444921
TI  - [Angiotensin-converting enzyme inhibition and cardiovascular prevention: more
      than twenty years of clinical success].
AB  - Angiotensin-converting enzyme (ACE) inhibitors are widely used for the treatment
      of cardiovascular disease since they improve blood pressure control in patients
      with hypertension and prolong survival in patients with acute myocardial
      infarction, asymptomatic left ventricular dysfunction and congestive heart
      failure. Most of the information about the therapeutic role of ACE-inhibitors has
      been achieved during the last 20 years since the publication of some pivotal
      trials mostly involving the use of ACE-inhibitors like captopril and enalapril.
      In particular the treatment with enalapril has considerably improved the clinical
      outcome of patients with either mild-to-moderate (SOLVD studies) or severe
      (CONSENSUS trial) congestive heart failure. The benefit of ACE-inhibitors in
      patients with congestive heart failure has also involved a remarkable reduction
      in the rate of hospitalization, thus contributing to improve the pharmaco
      economic approach to the disease. Most of the beneficial effect of ACE-inhibitors
      in clinical practice is dependent on their capacity of inhibiting the renin
      angiotensin system, although some recent trials have supported a primary role for
      such drugs (in particular enalapril) in the prevention of atrial fibrillation.
      After more than 25 years from their discovery, ACE-inhibitors must be again
      considered among the first-line treatment in many patients with cardiovascular
      disease.

PMID- 16444922
TI  - [Atrial fibrillation and cardioversion: role of transesophageal
      echocardiography].
AB  - The most common cardiac arrhythmia is atrial fibrillation (AF). Echocardiography
      has been an important tool in the evaluation of patients with AF. Transesophageal
      echocardiography (TEE) offers excellent visualization of the atria and accurate
      identification or exclusion of atrial thrombi. Patients undergoing cardioversion
      are treated conventionally with therapeutic anticoagulation for 3 weeks before
      and 4 weeks after cardioversion to decrease the risk of thromboembolism. A TEE
      guided strategy has been proposed as an alternative that may lower stroke and
      bleeding events. Patients without atrial thrombus by TEE are cardioverted on
      achievement of therapeutic anticoagulation, whereas cardioversion is delayed in
      patients with any thrombus. The two management strategies comparably lower the
      patient's embolic risk when the guidelines are properly followed. The TEE-guided
      approach offers the advantage of simplified anticoagulation management and may
      lower the incidence of bleeding complications.

PMID- 16444923
TI  - [Economic impact of cardiac resynchronization therapy in patients with heart
      failure. Available evidence and evaluation of the CRT-Eucomed model for analysis
      of cost-effectiveness].
AB  - Several clinical trials show that cardiac resynchronization therapy (CRT) in
      patients with moderate-severe heart failure increases survival, improves quality
      of life and reduces hospital admissions. The high cost of this new technology,
      incurred by health organizations at the moment of the implant, requires to assess
      whether its use is economically rational for the Italian Health Service. The
      paper summarizes evidences of the impact of CRT on the use of hospital resources
      and on quality of life, and presents a model to calculate incremental costs per
      quality adjusted life years (QALYs) gained in patients with moderate-severe heart
      failure treated with optimal medical therapy. The model is based on efficacy data
      drawn from clinical trials and on other information concerning the Italian
      context collected and validated by a team of experts from Assobiomedica and the
      Italian Federation of Cardiology. The model estimates that the incremental cost
      per QALY gained attributable to CRT is Euro 63,225 if all effects (years of life
      gained, increased quality of life and reduction of hospital costs) are censored
      at the end of the first year after the implant and Euro 21,720 if all effects are
      censored at the end of the third year. Cost-effectiveness of CRT is thus strongly
      dependent upon the duration of its effects: longer benefits of the therapy
      compensate initial costs and thus make the technology more cost-effective. In
      order to get better estimates of the economic profile of CRT it is required to
      collect more precise data from routine practice on survival, quality of life and
      hospital resources. The model presented can be easily adapted to take into
      account new evidence and to calculate cost per QALY gained in regional and local
      contexts.

PMID- 16444924
TI  - [Impact of reperfusion strategies on in-hospital outcome in ST-elevation
      myocardial infarction in a context of interhospital network: data from the
      prospective VENERE registry (VENEto acute myocardial infarction REgistry].
AB  - BACKGROUND: Primary angioplasty (pPCI) is the most effective reperfusion
      treatment of acute ST-elevation myocardial infarction (STEMI), but logistic- and
      organization-related problems could affect the outcome. The aim of this study was
      to investigate the in-hospital outcome according to reperfusion strategy in the
      Veneto Region cardiology network. METHODS: A treatment protocol, aimed to treat
      patients with high-risk STEMI by pPCI on-site or after transport, was developed
      and shared by the majority of cardiology departments in the Veneto Region. Data
      of all consecutive patients with STEMI were prospectively recorded during a 6
      month period. RESULTS: 999 patients with symptom onset < 12 hours were admitted
      to the 28 participating hospitals: 860 were treated on-site and 139 were
      transferred from the admitting hospital to an interventional center for PCI.
      Overall, 82% of patients were treated with reperfusion therapy. Ten patients died
      immediately before any treatment could be initiated. In 170 patients who did not
      receive any reperfusion treatment, in 302 patients who received fibrinolysis (and
      eventually rescue PCI) and in 517 patients sent to pPCI, the following in
      hospital outcome was observed respectively: mortality rate 10, 6.95 and 6.57%;
      reinfarction rate 0.6, 1 and 0.4%; incidence of stroke 1.7, 1.4 and 0.9%; the
      need for urgent revascularization procedure 6.5, 10 and 2.3%. After adjustment
      for confounding variables, the in-hospital occurrence of the combined events was
      significantly lower in patients treated with pP-CI (odds ratio 0.33, confidence
      interval 0.20-0.53, p < 0.01) as well as a trend for a reduced in-hospital
      mortality was observed (odds ratio 0.51, confidence interval 0.26-1.03, p =
      0.06). CONCLUSIONS: In the VENERE registry, patients treated with pPCI had a
      better in-hospital outcome as compared to those treated with fibrinolytic
      strategy.

PMID- 16444925
TI  - [Outpatient medical and nurse management program in patients with chronic heart
      failure in a large territorial area in Piedmont. Four years of follow-up].
AB  - BACKGROUND: Chronic heart failure is the leading cause of hospitalization and
      readmissions. In the last years many strategies based on the interaction of multi
      competence programs have been evaluated to improve its management. METHODS: We
      evaluated the feasibility of an outpatient management program for patients with
      chronic hearth failure jointly treated by hospital, territorial cardiologists,
      nurses and primary physicians in a large area of Piedmont. Between January 2001
      and January 2005, 122 consecutive patients (26.2% female, mean age 66 +/- 11
      years) with chronic heart failure were enrolled in the study. Etiology was:
      coronary heart disease 40.2%, dilated cardiomyopathy 18%, hypertension 18%,
      unknown 14%, valvular heart disease 4.9%, other 4.9%. Cardiologists were expected
      to assess etiology, to perform instrumental examinations and titration of beta
      blockers; nurses to reinforce patient education to monitor adherence to
      pharmacological and dietary therapy. Patients were subsequently followed by
      primary physicians. The endpoints were to compare: 1) hospitalization and
      emergency department admissions in the 12 months before the first evaluation and
      every year after referral; 2) Minnesota questionnaire, NYHA functional class,
      pharmacological therapies at the referral time and at the end of follow-up.
      RESULTS: One hundred and fifteen patients were followed for 47 +/- 1.5 months
      (5.6% drop out). Thirty-four patients died (29.5%), 11 non-cardiac causes, 14
      congestive heart failure, 6 sudden cardiac death, 3 cardiac transplantation.
      Ejection fraction improved from 31 +/- 10 to 36 +/- 12%. Emergency department
      admissions and hospitalizations decreased from 54 and 56 respectively in the year
      before the first evaluation to 14 and 21 per year (p < 0.001). NYHA classes I-II
      improved from 65.5 to 87.7% and NYHA classes III-IV were reduced from 34.5 to
      12.3%. The Minnesota score decreased from 25 to 21.9. Patients treated with ACE
      inhibitors + angiotensin II receptor blocker therapy increased from 91 to 96%,
      beta-blockers from 35.2 to 69%, potassium sparing drugs increased from 54 to 64%.
      CONCLUSIONS: Our study showed that a medical and nurse outpatient management
      program for patients with chronic heart failure, also in a large urban and
      country area, decrease number of hospitalizations and improve functional class
      and adherence to medical therapy. These results kept constant over time in the
      subsequent 4 years.

PMID- 16444926
TI  - [Persistent left superior vena cava. Follow the yellow brick road...].

PMID- 16444927
TI  - Retropubic nerve and seminal sparing radical prostatectomy for recurrent bladder
      neck-prostatic urethra strictures.
AB  - OBJECTIVES: To verify if nerve and seminal sparing radical prostatectomy could
      represent surgical solution for iatrogenic bladder neck prostatic urethra
      contracture without external sphincter involvement. MATERIAL AND METHODS: At our
      institution 4 patients have been submitted to nerve and seminal sparing radical
      prostatectomy for recurrent bladder neck-prostatic urethra contracture following
      TURP for middle size adenoma. In all cases bladder neck was reconstructed and a
      20F silicon catheter was left in place for two weeks to stint the vesico-urethral
      anastomosis. RESULTS: In all cases no significant perioperative complications
      were experienced. A normal voiding urethrogram preceded removal of the catheter
      14 days postoperatively. Urinary continence was recovered by all of the patients.
      Uroflowmetry was persistently normal at periodic controls. With a mean follow-up
      of 36.3 months, no patient complained of symptomatic recurrence of urinary
      obstruction. In three previously potent patients, sexual activity with
      satisfactory intercourse was maintained. CONCLUSION: Even though our experience
      is very limited in terms of number of patients and length of follow-up, we think
      that nerve and seminal sparing radical prostatectomy, because of the limited risk
      of major complications and the good result in terms of preservation of both
      urinary continence and erectile function, can be a reasonable solution for
      iatrogenic bladder neck-prostatic contracture after prostatic surgery for BPH.

PMID- 16444928
TI  - A more effective TR systematic biopsy of the prostate associated with power
      doppler ultrasonography (PDU): technical and morphological aspects.
AB  - OBJECTIVES: It is by now ascertained how PDU improves the effectiveness of
      systematic biopsy of the prostate. We have attempted to find better technical and
      imaging methods to optimise results. MATERIAL AND METHODS: We associated echo
      biopsy with PDU on 131 patients. 64 patients (48.85%) showed prostate Ca. Their
      age was between 53 and 84 (av. 71.7) with PSA ranging from 1.14 and 59.7 (r.
      9.,55 +/- 11.99 ng/ml). We then tried to locate in each sector areas of altered
      vascularization. RESULTS: In 34 cases (53.12%) we found hypo/hyper/iso reflecting
      areas surrounded by numerous vessels and crossed by one or more vascular branches
      (usually 2-3). In 8 cases (12.5%) we found hypo/hyper vascular echogenic
      virtually avascular, i.e. only a small perforating or surrounding branch. In 13
      cases (20%) we found an aspecific and often widespread hyper-vascularization not
      associated to echographically atypical areas, bilateral in 4 cases. In 9 cases
      (14%) we did not find evident vascular alterations during PDU. Through the
      correlation of power Doppler ultrasonography images with histology we noticed
      that the area of altered vascularization was positive to Ca in 38 patients
      (59.37%) whereas the same was not true in 5 patients (7.8%), and finally in 21
      patients (32.8%) the echo-doppler results (12 hypervascular and 9 "normal") was
      too aspecific to allow any kind of histomorphologic correlation. DISCUSSION:
      There are no pathognomonic patterns detectable through PDU for prostate Ca;
      although in the light of the above data it is safe to assume the existence of PDU
      detectable vascular alterations that in a good number of cases are not always
      neoplastic but prostatic disease which often coincide (about 60%) with cancer.
      The association of systematic biopsy and PDU helps highlight these areas thereby
      considerably improving diagnoses.

PMID- 16444929
TI  - Penile Doppler ultrasound assessment of the cavernous arteries.
AB  - OBJECTIVE: To evaluate the possible relationship between the basal and dynamic
      diameter of the cavernous arteries and altered peak diastolic (PDV) and systolic
      values (PSV) in patients undergoing penile Doppler ultrasound for differential
      diagnosis of erectile dysfunction (ED). MATERIALS AND METHODS: From December 2003
      to December 2004 we examined 132 consecutive patients suffering from erectile
      dysfunction and 30 controls. All patients underwent penile Doppler ultrasound in
      basal and dynamic conditions and all the examinations were performed by
      measurements of the cavernous arteries diameters in basal and dynamic conditions.
      RESULTS: In the 30 healthy controls the mean cavernous arteries diameter was 0.82
      mm (range 0.6-1.3 mm) on the right and 0.8 mm (range 0.5-1.25 mm) in basal
      conditions vs 1.30 mm (range 0.9-1.6 mm) on the right and 1.25 on the left (range
      0.9 -1.60 mm) in dynamic conditions after injection of 10 microg. In the 132
      patients with a diagnosis of organic ED, the mean diameter was 0.70 mm (range 0.3
      1.3 mm) on the right and 0.76 mm (range 0.3-1.24) on the left in basal conditions
      vs 1.21 mm (range 0.8-1.93 mm) on the right and 1.24 mm (range 0.9-1.66 mm) on
      the left in dynamic conditions after injection of 10 microg. CONCLUSION: In our
      experience, assessment of the cavernous arteries in basal and dynamic conditions
      provides important additional data. Altered basal and dynamic values are
      predictive of anomalous PDV and PSV findings.

PMID- 16444931
TI  - Could the sextant prostate biopsy be replaced by transurethral resection?
AB  - AIM OF THE STUDY: We studied patients with elevated serum levels of prostate
      specific antigen (PSA) and low urinary tract symptoms (LUTS) aiming to determine
      whether histological examination after transurethral resection of the prostate
      (TURP) could detect prostate cancer (PC) missed by previous routine transrectal
      ultrasound (TRUS) guided sextant prostate biopsies. MATERIALS AND METHODS: We
      considered 98 consecutive men with serum tPSA level from 4 to 12 ng/mL who were
      submitted to TRUS-guided sextant biopsies. RESULTS: PC was detected in 28 (28.6%)
      cases at first biopsy. Of the 70 patients who were not proven to have PC, 49
      underwent TURP for severe LUTS. The median volume of resected tissue was 14.2 g
      (11.0-19.4 g). PC was detected in 12 (24.5%) specimens of resected tissue after
      TURPF PC lesions diagnosed after TURP were located mainly in the TZ, with cancer
      volume not more than 0.108 cm3. In 21 patients with negative first biopsy who did
      not underwent TURP was prescribed a conservative treatment and follow-up. In 7 of
      those patients elevated serum PSA levels were revealed during the follow-up. A
      second sextant TRUS-guided biopsy demonstrated PC in 4 patients. The remaining
      patients showed no significant increase in their serum PSA level and are still
      observed in present days. CONCLUSIONS: The sensitivity of routine sextant TRUS
      guided biopsy of the prostate is not high enough and the detection of cancer is
      not warranted using this standard procedure. TURP can detect cancers in TZ of the
      prostate, when performed for treating LUTS in patients with negative prostate
      biopsy. In patients who did not need TURP: only in 4 out of 21 patients with a
      negative first biopsy a repeat biopsy demonstrated PC. In conclusion TURP is
      recommended for all the patients with enlarged prostate, negative prostate biopsy
      and severe LUTS after unsuccessful conservative treatment.

PMID- 16444930
TI  - Testosterone supplementation in hypogonadal men: our personal experience.
AB  - INTRODUCTION AND OBJECTIVES: Around thirty years of age, we assist to a
      physiological, progressive and slow involution of the testicular function
      accompanied by a fall of the plasmatic levels of testosterone. Rarely
      hypogonadism is manifest in so young age with signs and symptoms, unless it is
      subsequent to severe events. After 50 years of age, it can present with a series
      of aspects that negatively influence the physical and sexual efficiency. The aim
      of this study is to prove if the replacement therapy with testosterone is able to
      restore a physiological gonadal function, without incurring in unpleasant side
      effects to prostate, liver and cardiac muscle. MATERIAL AND METHODS: We report
      our experience on 123 patients over 60 years of age (mean age 71) and 12 patients
      over 30 (mean age 37). These last ones were submitted to andrologic assessment
      after genital trauma. Both groups of patients have reached our observation from
      December 2000 to June 2003 for important asthenia and decrease of libido
      associated with impairment of secondary sexual characters and erectile deficit of
      various degrees. Respectively 76 and 12 patients did not show contraindications
      for testosterone therapy and they began injections with testosterone for at least
      6 months. RESULTS AND CONCLUSIONS: Although compliance to testosterone treatment
      has not been equal in the time in all the subjects, undesirable effects are not
      highlighted. All the patients have reported complete or partial recovery of
      physical efficiency and improvement of sexual life, evaluated by means of IIEF
      scale and ADAM-AMS questionnaires. The replacement pharmacological treatment with
      testosterone improves the physical and sexual performance of the adult patient
      affected by symptomatic hypogonadism.

PMID- 16444932
TI  - Cystic dysplasia of the rete testis associated to cryptorchidism: a case report.
AB  - A case of cystic dysplasia of the rete testis (CDRT) is reported. Nine months
      after right orchidopexy, a 10-year-old boy presented a palpable mass in the
      ipsilateral hemi-scrotum. Preoperative ultrasound showed a cystic lesion
      involving almost the whole testis. Radical orchidectomy was performed and at
      gross examination a hilar multiloculated cystic lesion was confirmed; microscopic
      examination showed cystic spaces lined by benign appearing monostratified
      epithelium with atrophy of the surrounding testicular parenchyma. These findings
      were consistent with the diagnosis of cystic dysplasia of the rete testis.
      Immunohistochemical investigation evidenced a pattern similar to that of a normal
      rete testis. Renal ultrasound and DTPA scintigraphy performed after pathological
      diagnosis documented the absence of the ipsilateral kidney. CDRT is a rare cause
      of scrotal swelling in the pediatric patient. When diagnosis is suspected, based
      on clinical and sonographic findings, conservative surgery may be considered.

PMID- 16444933
TI  - A case of medullary sponge kidney (Cacchi-Ricci disease) mimicking a renal mass.
AB  - Medullary sponge kidney (MSK) is an uncommon benign congenital disorder,
      generally asymptomatic. In symptomatic patients the diagnosis is usually made by
      excretory urography performed in the most frequent complications such as renal
      stones, urinary tract infections and haematuria. Excretory urography can be very
      characteristic, showing cystic collections of ectatic collecting ducts like
      "bunches of grapes" or "bouquet of flowers". When haematuria represents the only
      symptom, and radiographic findings are not characteristic of MSK, the
      differential diagnosis with a renal tumor can be very difficult. We report a case
      of MSK that underwent nephrectomy since clinical and radiological features
      mimicked a renal tumor.

PMID- 16444934
TI  - Incidence and treatment of complications in nephron sparing surgery.
AB  - Conservative renal surgery (enucleation or segmentary resection) has become the
      gold standard treatment for small and peripheral malignant kidney lesions or in
      cases of reduced renal function or bilateral lesions. The aim of this study is to
      evaluate the incidence and treatment of complications of this technique in our
      experience. MATERIALS AND METHODS: Between March 1997 and March 2005, 159
      patients aged from 23 to 77 years (median 66 years) underwent conservative renal
      surgery. In 123 patients the indication was elective and in 36 imperative. In 92
      patients lesions were located in the upper pole, 41 in the lower pole and 24 were
      meso-renal . Two patients suffered from von Hippel-Lindau (VHL) disease and
      therefore presented multicentric lesions. Mean lesion diameter was 3 cm ( range 1
      to 9 cm). Retroperitoneal access with flank incision was the approach used in all
      patients. In 124 patients the technique consisted of enucleation with hypothermia
      from contact with sterile ice. Time to ischaemia was between 12 - 40 minutes. The
      collecting system was opened in 23 patients. RESULTS: Twelve cases of
      perioperative complications were encountered in this group of patients. Major
      complications were: two massive hemorrhage, two arteriovenous fistula, one lesion
      of the ureter, five cases of acute kidney failure. The two massive bleedings
      occurred within the first eight hours after surgery and necessitated surgical
      intervention to check a bleeding perinephric vessel. The arteriovenous fistulas,
      which occurred on the seventh and tenth postoperative day, were treated with
      selective percutaneous sclero-embolisation. The five acute kidney failures
      involved patients with functional or anatomical solitary kidney. No patient
      required dialysis in the post-operative period. Ureter lesion characterised the
      post-operative course of one solitary kidney patient affected by voluminous
      angiomyolipoma. Anuria and urine emission from drainage lead to exploratory
      lumbotomy which evidenced an iatrogenic lesion of the lumbar ureter that was
      treated with termino-terminal anastomosis. No other major complications were
      noted, with the exception of delay in intestinal canalization occurring in a 74
      year old patient, and a wound infection in a patient with previous renal abscess
      associated to infundibular lithiasis and caliceal exclusion. There were no
      postoperative deaths. CONCLUSIONS: Conservative renal surgery is a valid
      alternative to radical surgery. In our study, as already reported in literature,
      surgical complications were slight in incidence and conservatively treatable.
      Therefore, nephron sparing surgery (NSS) can be performed with safety and maximum
      preservation of renal function.

PMID- 16444935
TI  - Percutaneous therapy of low stage and grade urothelial neoplasia: long-term
      follow up.
AB  - Nephroureterectomy with the excision of the ipsilateral ureteral orifice and
      bladder cuff has been considered the standard treatment of the urinary upper
      transitional cell carcinoma. With the advent of sophisticated techniques for the
      endo-urologic management of many benign urologic diseases of the upper tract,
      there has been growing enthusiasm for the application of these same techniques in
      the management of upper tract TCC, which is also supported by recent advances in
      the development of small calibre telescopes with improved optics and the
      development of small calibre adjunctive instruments and laser fibers. A large
      number of cases published in the literature has confirmed the safety and efficacy
      of percutaneous treatment in selected patients with upper tract TCC of low grade
      and stage. Between 1997 and 2005 we treated 62 pts (37 pelvic transitional cell
      carcinoma and 25 ureteral). 4 pts (5 renal units: 4 T1G2 and 1 TaG1) underwent
      percutaneous resection for a tumor in a solitary kidney (2 cases), one case for
      bilateral neoplasm, and in the other case the lesion was unilateral with chronic
      renal failure. After preoperative evaluation, (excretory urography, computerized
      tomography and ureteroscopy with biopsy to confirm the low stage and grade of the
      lesion) the tumor was resected using an Amplatz sheat of 26-30 Fr and a 24 Fr
      resectoscope to keep a low intra-caliceal pressure. The tumor base was biopsied
      and fulgurated After 48 h, contrastography to assure integrity of the urinary
      system was performed and Mitomycin C was infused over 24 h. Second-look
      nephroscopy with multiple biopsies was performed in all cases 7 days later and 8
      Ch nephrostomy was placed. If the biopsies resulted negative the patient was
      submitted to 6 weekly endocavitary instillation of BCG through the nephrostomy
      tube. All pts at a mean follow up of 71 months were tumor free. One patient
      presented a bladder relapse after 83 months. No complication of percutaneous
      resection was observed. The endocavitary instillations were well tolerated. In
      our experience the percutaneous approach is safe and useful in neoplastic lesions
      of low grade and stage and should be considered as first line therapy in selected
      patients. Adjuvant topical therapy appears efficacious and some complications may
      be avoided by maintaining low intracavitary pressures during administration.

PMID- 16444936
TI  - Conservative treatment of high grade superficial bladder tumours.
AB  - AIM OF THE STUDY: To review our previous experience in the treatment of high
      grade superficial bladder tumour. MATERIAL AND METHODS: Data from 71 consecutive
      patients (12 women and 59 men) with high grade (G3) superficial (Ta-T1) bladder
      tumour were considered. After endoscopic treatment 31 patients received
      intravesical immunotherapy with Bacillus Calmette Guerin (BCG), 14 patients were
      treated with a combined scheme of intravesical chemotherapy and immunotherapy and
      respectively 3 patients and one patient with intravesical chemotherapy with
      mitomycin (MMC) or epirubicin (EPI) alone. A group of 16 patients received no
      further treatment after TUR and other 6 patients was treated with systemic
      chemotherapy or radiotherapy. Patients were followed up with urine cytology and
      cystoscopy every three months, renal sonography every six months and intravenous
      pyelography every 2 years or in the case of positive cytology associated with
      negative cystoscopy. RESULTS: Out of 16 patients treated with TUR alone 11
      recurred (69%) BCG was initiated in 31 patients and 12 out of them suffered
      recurrences (42%), whereas 7 out of 14 patients who had combined epirubicin/BCG
      therapy developed recurrences (50%). Out of 19 patients who recurred after
      treatment with BCG alone or combined with epirubicin, five underwent immediate
      cystectomy and other five delayed cystectomy after a second course of
      intravesical therapy. In the latter group higher pathological stages were
      observed. We were not able to identify any factor predictive of recurrence after
      BCG treatment: sex (M 16/40 vs F 3/5 p = 0.35), stage (Ta 1/6 vs T1 18/39 p =
      0.11), associated carcinoma in situ (CIS) (No CIS 1/8 vs CIS 18/37 p = 0.11),
      multifocal (single 13/31 vs multiple 6/14 p = 1.00), age (66.8 +/- 7.8 vs 62.9 +/
      11.9 years p = 0.19) and number of previous recurrences (0.42 +/- 0.90 vs 1.31
      +/- 2.16 p = 0.06). Under chemotherapy (MMC or EPI) all 4 treated patients
      suffered recurrences (100%). Out of all recurrent patients after conservative
      treatment of an high grade superficial bladder tumours, seven presented tumours
      with a low grade histology (downgrading). In all but one of these patients an
      high grade tumour recurred within 30 months. CONCLUSIONS: The adoption of a
      correct strategy of intravesical metaphylaxis with BCG allows to spare cistectomy
      in up to 60% of the patients with high grade superficial bladder carcinoma and
      the optimisation of treatment protocols will lead to even more effective results.
      However this tumour still demands the highest level of attention in the follow up
      and in the case of recurrence primary conservative treatment with BCG should be
      promptly converted to radical surgical treatment considering that the development
      of less invasive surgical procedures has reduced the impact on the patient's
      quality of life

PMID- 16444937
TI  - Prospective comprehensive assessment of sexual function after retropubic non
      nerve sparing radical prostatectomy for localized prostate cancer.
AB  - OBJECTIVES: This prospective study was undertaken to assess sexual function
      according to a multidisciplinary comprehensive approach in patients with
      localized prostate cancer who were treated with radical prostatectomy. MATERIALS
      AND METHODS: Patients with localized prostate cancer scheduled to undergo
      retropubic radical non nerve sparing prostatectomy participated to the study.
      International Index of Erectile Function (IIEF) and Self-rating Depression Scale
      (SDS) questionnaires were administered and patients were interviewed by a
      psychologist about their sexual function before and 1 month and 3 months after
      surgery and underwent nocturnal penile tumescence (NPT) monitoring for 3 nights
      before and 3 months after radical prostatectomy. After surgery patients were
      offered sexual counselling and were encouraged to experiment with oral treatment
      for erectile dysfunction. At 24 month follow up patients were interviewed asking
      for information PSA value, continence and sexual status. RESULTS: At basal IIEF
      score showed erectile dysfunction at various degree in 40%, SDS score
      demonstrated a mild depression in 10% and NPT tests showed a number or erectile
      episodes less than 3 in 30%, a total time of erection less than 60 minutes in 43%
      and a degree of rigidity less than 70% in 66%. IIEF scores were inversely related
      to SDS scores (r = -0.43, p < 0.012) and SDS scores were inversely related to
      time of erection at NPT (r = -0.44, p = 0.016). The mean basal IIEF score was
      significantly higher than the 1-month IIEF (p = 0.000) and 3-month IIEF score (p
      = 0.001) and the mean basal SDS score was significantly higher than the 3-month
      SDS score (p = 0.011). The mean degree of erections (p = 0.000), total time of
      erection (p = 0.004) and degree of erection (p = 0.003) at basal were
      significantly higher than at 3-month follow up. At 24 month follow up five
      patients replied that they were not able to achieve any erection (group A), 4
      were able to achieve an erection only after intracorporeal injection of
      prostaglandins (group B), 3 were able to achieve erection after oral treatment
      with sildenafil and only one stated to be able to achieve spontaneously an
      erection sufficient to sexual intercourse (group C). The mean values of basal
      IIEF and SDS score at basal and the degree of erection at basal were not
      significantly different in the three groups whereas the mean number of erections
      and the mean total time of erection at basal NPT tests were significantly higher
      in group C than in group A and B. CONCLUSION: Severe erectile dysfunction was
      observed in most patients after retropubic radical non nerve sparing
      prostatectomy, but 50% of candidates for radical treatment presents with abnormal
      erectile function before surgery when appropriately studied. Patients who will
      recover erectile function could be identified by NPT test before surgery.
      Depression associated with the fear for intervention is related with erectile
      dysfunction measured by IIEF scores before surgery, but depression index scores
      improve after surgery showing that the role of depression in the maintenance of
      erectile dysfunction is marginal. Sexual counselling and oral treatment
      facilitate recovery after surgery in patients with optimal erectile function
      before treatment.

PMID- 16444938
TI  - Vaginal repair of vesico-vaginal fistulas: our experience.
AB  - Vesico-vaginal fistula repair is feasible both with abdominal and vaginal
      approach. We report our experience in vaginal repair of 34 vesico vaginal
      fistulas. Twenty-eight out of 34 fistulas have been treated by vaginal repair
      (82.3%) (in 2 cases after an attempt of endoscopic repair), 4/34 (11.8%) by
      abdominal repair and 4/34 (11.8%) by endoscopic repair with good outcome in 2
      cases. In 96% of fistulas treated by vaginal repair (27/28) we obtained a
      complete recovery; in one patient we observed fistula recurrence after 2 months
      from the operation. Four patients were treated by abdominal approach: in two
      complex patients with vesico-uretero-vaginal fistula, the repair was associated
      with entero-cystoplasty and ureteral reimplantation; in one case of huge fistula
      following cesarean section (7 cm) a vesical flap was used; in one case we
      repaired a recurrent fistula in orthotopic ileal neobladder: A good outcome was
      achieved in all cases. Vaginal approach is less aggressive, well accepted by
      patients and can lead to lower legal issues. Abdominal surgery is mandatory in
      complex situations, when the fistula is big (> 4 cm) or when ureteral orifices
      are involved.

PMID- 16444939
TI  - [The epiglottis, a glosso-laryngeal structure: an anatomic study of its
      innervation].
AB  - The epiglottis is known as a laryngeal structure. The authors studied the
      innervation of epiglottis using the Sihler method on six human epiglottises.
      Innervation of the epiglottis depended on the rami from the vagus,
      glossopharyngeal and hypoglossal nerves. By its innervation, epiglottis seems to
      be a glosso-laryngeal structure, as is confirmed by embryology, histology and
      clinical applications.

PMID- 16444940
TI  - [Supracondylar process and supratrochlearforamen of the humerus: a case report
      and a review of the literature].
AB  - The authors present a case where the main variants of the humerus were associated
      on the same specimen: the supracondylar process and the supratrochlear foramen.
      The supracondylar process, a bony prominence situated on the anteromedial surface
      of the humerus in the vicinity of the medial epicondyle, could be at the origin
      of ulnar or median nerve and brachial artery compression syndromes, especially
      when associated with Struthers' ligament. MATERIAL AND METHOD: The anatomic
      specimen was discovered accidentally during a larger study aimed at establishing
      a current norma anatomica and morphometry of the humerus. The supracondylar
      process and the supratrochlear foramen were morphologically and morphometrically
      analyzed. RESULTS AND DISCUSSION: The supracondylar process was situated on the
      anteromedial surface of a left humerus, roughly 5 cm above the medial epicondyle.
      It was 12.4 mm in length, mediodistally directed. The supratrochlear foramen was
      situated above the lateral part of the humeral trochlea, just adjacent to the
      middle branch of trifurcation of the anterior border of the humerus. It was ovoid
      in shape with the long axis transversally (6.3/3.7 mm). CONCLUSIONS: Presentation
      of such variants contributes to increasing the anatomical data capital and might
      be important for diagnosis of peripheral neurovascular compression syndromes.

PMID- 16444941
TI  - [The mesorectum: an anatomical entity that is difficult to evaluate with MRI].
AB  - The preoperative assessement by magnetic resonance imaging (MRI) of mesorectum
      involvement could improve the treatment strategy for patients with rectal cancer.
      However, the anatomical definition of the mesorectum remains controversial and
      consequently the accurracy of its analysis by preoperative imaging workup is
      still unsatisfactory. The aims of this study were to define the mesorectum
      anatomically and to assess whether it could be evaluated accurately by MRI. Total
      mesorectal excision was performed in 37 patients with rectal cancer. The
      mesorectum was inked for anatomical analysis, which was performed before and
      after fixation in formalin. The mesorectal thickness was measured anteriorly,
      posteriorly and laterally. Mesorectal involvement was defined by the shortest
      distance from the outermost part of the tumour to the lateral mesorectal margin.
      The anatomical measures were compared to those evaluated by preoperative MRI. In
      middle rectum, the anatomical analysis showed that the maximal mesorectal
      thickness was 60 and 20 mm posteriorly and anteriorly, respectively. In low
      rectum, the mesorectum was very thin and its maximal thickness was less than 10
      mm anteriorly and posteriorly in all cases. The mesorectal involvement was less
      than 2 mm in 23% of cases. In terms of mesorectal involvement, there was good
      agreement between anatomical analysis and MRI for middle rectum. In contrast, the
      agreement was fair for low rectum. This anatomical analysis could explain the
      poor performance of MRI in the assessement of mesorectum involvement in low
      rectum.

PMID- 16444942
TI  - [Anatomic study and advantages of the free rectus abdominis flap for head and
      neck reconstruction].
AB  - INTRODUCTION: The main goal of using the free flap is to be able to carry out
      extensive surgical resection resulting in good functional outcome. The aims of
      this study were to define the best area for free rectus abdominis harvest and to
      assess its value in head and neck reconstruction. MATERIAL AND METHODS: Twenty
      rectus abdominis flaps were studied in ten fresh cadavers. A review of the
      literature of the free rectus abdominis flap in head and neck reconstruction
      yielded the main recipient sites and complications (flap necrosis and
      postoperative abdominal hernia). A reconstruction was performed after near total
      glossectomy. RESULTS: With seven perforators and four cutaneous branches of
      intercostal nerves, the paraumbilical region is the best area to harvest this
      flap. The rectus abdominis free flap seems to be adapted for near total
      glossectomy reconstruction. Previous studies reported that this flap was
      essentially used for oropharynx and skull base reconstruction. The main
      complications are flap necrosis (4%) and abdominal hernia (3%). CONCLUSION: The
      paraumbilical rectus abdominis free flap is reliable and easy to use with a two
      team approach in head and neck reconstruction with moderate donor site morbidity.
      It is useful for reconstruction of large defects of the oropharynx and skull
      base. Sensory-motor reinnervation superiority for deglutition in tongue
      reconstruction still needs to be evaluated.

PMID- 16444943
TI  - [Duplication of the inferior vena cava: anatomical dissection and clinical
      implications].
AB  - The duplication of the inferior vena cava is often incidentally discovered during
      radiological studies. The presence of this anomaly can be mistaken for
      retroperitoneal adenopathy. Its knowledge allows to avoid hemorrhagic
      complications during retroperitoneal surgery. An anatomical dissection of a
      duplication of the inferior vena cava is presented. Embryogenesis and variations
      are described. Radiological and clinical implications are discussed.

PMID- 16444944
TI  - [The human body and the computer as pedagogic tools for anatomy: review of the
      literature].
AB  - Since the first dissections, the human body has been the main tool for the
      teaching of anatomy in medical courses. For the last 30 years, university anatomy
      laboratory dissection has been brought into question and the total hours of
      anatomy teaching have decreased. In parallel, new technologies have progressed
      and become more competitive and more attractive than dissection. The aim of this
      review of the literature was to evaluate the use of the human body as a pedagogic
      tool compared to today's computer tools. Twenty comparative studies were
      reviewed. Their analysis showed that the human body remains the main tool in
      anatomy teaching even if anatomic demonstration (prosection) can replace
      dissection, and that the computer tools were complementary but not a substitute
      to dissection.

PMID- 16444945
TI  - [From bench to bedside: should we believe in the efficacy of stem cells in
      cerebral ischaemia?].
AB  - Stroke is the third cause of mortality and the leading cause of morbidity in
      industrialized countries. At the present time, ischaemic stroke is treated at the
      acute phase by thrombolysis with a recombinant of the tissular-plasminogen
      activator, which must be administered within the first 3 hours. Cell therapy,
      while using the self-renewal and differentiation potentials of stem cells, brings
      new hope for the long-term care of ischaemic stroke. Animal studies show that
      stem cells improve functional deficit without reduction of infarct volume and
      with very rare differentiation of the stem cell. These experimental studies
      suggest that stem cells would support cerebral plasticity via growth factor
      production and stimulation of endogenous mechanisms of local repair. Assessment
      of effectiveness and safety in the use of stem cells in cerebral ischaemia still
      require thorough investigation before clinical trials in humans can be developed.

PMID- 16444946
TI  - [Representation of animals in the paintings of Albert Anker (1831-1910)].
AB  - Albert Anker broke with the old tradition to become a veterinarian and studied to
      be a painter at Paris. He lived from 1831-1910 and is one of the best known
      painters of Switzerland. His work consists of rough outlines, drawings,
      watercolours and numerous oil paintings (more than 800) in all fields of
      painting. In particularAlbert Anker gained great esteem with his numerous
      portraits and interpretations of the rural daily life (genre painting). Rarely
      pictorial representations of animals are to be found on his paintings in opposite
      to people. Especially these animals don't feature the fidelity of the details
      which is so typically for Albert Anker. Three examples demonstrate this lack and
      in what it consist of. An attempt will be made to explain the cause of this
      phenomenon.

PMID- 16444947
TI  - [The veterinary pharmacopoeia of Peter Bodmer, blacksmith and cattle doctor in
      Darligen 1836].
AB  - The manuscript entitled "My pharmacopoeia Peter Bodmer in Darligen--1836"
      [Arzeneybuch mein Peter Bodmer in Darligen pro. 1836] contains a collection of a
      total of 227 remedies for the treatment of cattle, horses, pigs and human beings.
      The author Peter Bodmer was born on 15 November 1811 in Darligen on the shores of
      Lake Thun and worked as a smith and a cattle doctor. The manuscript cannot offer
      a full overview of the therapeutic possibilities in veterinary medicine at that
      time. The remedies mainly describe the peroral dispensing of herbal preparations.
      The use of medicinal plants, however, would only partially measure up to modern
      phytotherapy. Bodmer's manuscript provides a certain insight into the traditional
      herbal folk remedies used on animals and humans in the rural Bernese Oberland at
      that time.

PMID- 16444948
TI  - [Veterinarians of Waadt confronted with the "war of cows"].
AB  - During spring 1966 the veterinary practitioners of the canton Waadt were
      confronted with the illegal import of bovine semen and cattle from France. The
      Societe Vaudoise des Veterinaires wrote an "open letter" to the former Federal
      Councillor Schaffner. This letter achieved a partially liberalization of the
      importation of bovine semen of foreign breeds.

PMID- 16444949
TI  - [Renaissance of equine dentistery, an abandoned discipline, which one tries to
      recover].
AB  - The author illustrates by the study of ancient texts the interest shown for
      equine dentistry since the age of times. The first detailed studies on the
      technique go back to the 17th century. The 19th and the beginning of the 20th
      centuries were fertile in instrumental as well as technical discoveries; it was
      the time of creativity, and he quotes authors like Gunther father and son, Frick,
      Goubaux and Barrier, Merllat, Cadiot, and Colyer with his enormous work on animal
      dentistry published in 1936. During and right after the 2nd World War, it is the
      time of desertion, with only one exception, Erwin Becker, who out of Berlin gives
      an extraordinary prestige to the dentistry. The beginning of the revival seems to
      go back to 1975-1980. At this point of time, non veterinarian "dentists" breach
      in, the moust famous being Dale Jeffrey, who opens a school, creates an academy
      and publishes a newspaper. The author reviews all the existing teaching method. A
      new professions is born, the dental technician, one hurdle remains how to
      integrate it within the world of the veterinarians? The author presents the
      British example, the best regulated. He also shows how the French National
      Veterinary Schools have restored the teaching of dentistry. The author regrets
      that the Medias glorify the dental technicians under the pompous and improper
      trade name "equine dentists", to the detriment of the veterinarians.

PMID- 16444950
TI  - What comes next? Scientists are now grapping with a major setback to stem cell
      research.

PMID- 16444951
TI  - Help for hackers. New guidelines say which drugs really kill a cough.

PMID- 16444952
TI  - Lights. Camera. Robert action!

PMID- 16444953
TI  - Let's talk Turkey.

PMID- 16444954
TI  - [Pathogenesis and infections in patients with defects in neutrophil functions].

PMID- 16444955
TI  - [Pathophysiologic roles of activated neutrophils in infections].

PMID- 16444956
TI  - [Immune system modulation by herpesvirus infection].

PMID- 16444957
TI  - [Significance of the stool occult blood test in patients with thrombotic disease
      under treatment with low dose aspirin].
AB  - We encountered lower gastrointestinal bleeding in 16 patients taking a low dose
      of aspirin and examined the effect of low aspirin dose on the stool occult blood
      test in 49 thrombotic patients (mean: 76.7 +/- 9.6 years old) including 39 with
      cerebral infarction, 8 with ischemic heart disease and 2 with atrial
      fibrillation. The mean aspirin dosage was 81 mg/day over a period of 6-288 weeks
      (mean: 86.4 +/- 66.9 weeks). Positive occult blood test was seen in 16/49
      (32.7%). Severe lower gastrointestinal bleeding was observed in one case (2%)
      with colon diverticulosis. Aspirin dosage per patient was significantly higher
      (p<0.01) in the occult blood test positive group (60.1 +/- 47.2 g) than in the
      occult blood test negative group (42.6 +/- 32.8 g). The positive ratio of occult
      blood test was significantly higher (p<0.01) in the aspirin and antithrombotic
      drugs-taking group (8/5; positive/negative) than in the aspirin-taking group
      (8/28; p/n), whereas it was not significant between the aspirin taking-group and
      aspirin not taking-group. The odds ratio between aspirin and antithrombotic drugs
      (warfarin, beraprost, cilostazol or ticlopidine)-taking group and the aspirin
      taking group was 3.47 (p<0.05). A low dose of aspirin was associated with a
      positive occult blood test. Aspirin should be carefully administered when patient
      has a diverticle or is taking other antithrombotic drugs.

PMID- 16444958
TI  - [Immunosuppressive therapy for adult aplastic anemia in a single institution
      study].
AB  - We evaluated the efficacy and long-term outcomes of immunosuppressive therapy
      (IST) in 50 adult patients with aplastic anemia at a single institution. Twenty
      one patients who had not responded to the first course of IST or relapsed after
      the initial response to IST were retreated with the second course of IST with
      antithymocyte globulin. The response and relapse rate of the initial IST were
      76.7% and 23.3%, respectively. The response rate of salvage IST was 61.9%.
      Overall survival at 10 years was 84.0%. Failure-free survival at 10 years was
      62.0%. Clonal or malignant diseases developed in 2 patients. Early deaths due to
      bleeding or infection were observed only in elderly patients. We conclude that
      most patients with aplastic anemia treated with IST show hematologic improvement
      and excellent long-term survival.

PMID- 16444960
TI  - [Long-term remission in an acute monoblastic leukemia patient with down syndrome
      after cord blood transplantation].
AB  - A 4-year-old boy with Down syndrome (DS) was diagnosed as having acute
      monoblastic leukemia (AML-M5a). Leukemic cells were CD33+, CD56+ and CD4+, with
      t(9;11) on cytogenetic analysis and MLL gene rearrangement. After 2 courses of
      induction therapy using an AML 99-Down protocol failed to obtain complete
      remission, the patient received cord blood transplantation from an HLA-matched
      donor (CBT) following a conditioning regimen comprising total body irradiation
      and cyclophosphamide. Only cyclosporin A was used for graft-versus-host disease
      prophylaxis. Stem cell transplantation may not be indicated for AML patient with
      DS in first remission, who display a high rate of life-threatening and fatal
      toxicity on therapy. This patient remained well controlled in complete remission
      for 4 years, representing a rare case of DS with chemotherapy-resistant AML
      successfully treated with a CBT.

PMID- 16444959
TI  - [Effective combination therapy of bortezomib and dexamethasone for two patients
      with refractory multiple myeloma].
AB  - We describe 2 cases of conventional therapy-resistant multiple myeloma (MM) that
      responded to bortezomib and dexamethasone therapy. Case 1: A 62-year-old woman
      with MM (IgG, kappa-type, stage IIIA) resistant to DMVM-IFN (dexamethasone,
      ranimustine, vincristine, melphalan, interferon-a), VAD (vincristine,
      doxorubicin, dexamethasone), high-dose melphalan with autologous peripheral blood
      stem cell transplantation (PBSCT) and thalidomide, received 2 courses of
      bortezomib treatment. In the first course, bortezomib alone was administered and
      then in the second course bortezomib was given in combination with dexamethasone.
      The patient's serum IgG level decreased from 8040 to 1020 mg/dl and the level of
      plasma cells in bone marrow was 1.2% after the treatments. Adverse reactions
      including rash, anemia, and thrombocytopenia occurred in the first course;
      however, they were milder in the second course combined with dexamethasone. Case
      2: A 43-year-old man with MM (IgD, gamma-type, stage IIA) resistant to
      conventional and high-dose chemotherapy with PBSCT as well as thalidomide
      therapy, received treatment with bortezomib alone and then in combination with
      dexamethasone. His serum IgD level decreased from 2140 to 623 mg/dl. He suffered
      adverse reactions such as fatigue, anemia, and thrombocytopenia in the first
      course, which were relieved in the second course. These results indicate that the
      combination of bortezomib and dexamethasone is effective in the treatment of
      refractory MM and that dexamethasone can reduce the adverse reactions of
      bortezomib.

PMID- 16444962
TI  - [Serum CA125 level associated with disease activity in a patient with follicular
      lymphoma].
AB  - We encountered a case of follicular lymphoma in a patient with high levels of
      serum CA125. On examination, abdominal lymph node swelling and hepatosplenomegaly
      were observed. The CA125 level decreased during treatment and was normalized at
      complete remission. An immunohistochemical assay of the lymphoma cells, however,
      failed to demonstrate any CA125. Several reports have described that CA125 might
      be produced by mesothelial cells in response to cytokines released by the
      lymphoma cells, and increased levels of CA125 have been significantly associated
      with abdominal involvement. It is possible that CA125 will become a useful marker
      in the observation of the progression of malignant lymphoma in the abdomen.

PMID- 16444961
TI  - [Successful treatment with drainage of hematoma and chemotherapy in a case of
      Burkitt leukemia presenting with subdural hematoma].
AB  - A 53-year-old male was admitted because of pancytopenia and chronic subdural
      hematoma. Bone marrow was hypercellular with 97% blasts, which expressed CD10,
      CD19, CD20, and immunoglobulin mu and gamma chains on the cell surface and had
      chromosomal abnormalities including t(8 ; 22)(q24 ; q11). The patient was
      diagnosed as having Burkitt leukemia. Because hemiplegia and disturbance of
      consciousness developed rapidly, the patient was treated with an emergency
      drainage operation followed by Hyper-CVAD therapy and achieved a sustained
      complete remission. Dural infiltration of leukemic cells as well as
      thrombocytopenia was implicated in the pathogenesis of the subdural hematoma,
      which contained numerous blasts.

PMID- 16444963
TI  - [Molecular mechanisms of autoimmune hemolytic anemia].

PMID- 16444964
TI  - [Paroxysmal nocturnal hemoglobinuria: mechanism of clonal expansion].

PMID- 16444965
TI  - [Immunosuppressive therapy of refractory anemia--clinical trials of cyclosporin A
      therapy in Japan].

PMID- 16444966
TI  - [Primary chronic myelofibrosis in the Japanese population].

PMID- 16444967
TI  - [Progress of the ATLL study: an overview].

PMID- 16444968
TI  - [Trial of front-line intensive chemotherapy followed by peripheral blood stem
      cell transplantation in high-intermediate and high risk non-Hodgkin's lymphoma
      patients].
AB  - High-intermediate (HI)- and high (H)-risk non-Hodgkin lymphoma was treated with
      front-line intensive chemotherapy followed by autologous peripheral blood stem
      cell transplantation (auto-PBSCT). Twenty-eight cases were enrolled after
      obtaining informed consent, from November, 1998 to October, 2003. Initial
      treatment was 2 or 3 cycles of CHOP-V regimen, followed by three high-dose
      therapy, one each of cyclophosphamide, methotrexate and etoposide. The final high
      dose therapy was a combination of ranimustine, ifosphamide and etoposide, which
      was followed by auto-PBSCT. Patients with a bulky mass received involved-field
      radiation therapy (IF-RT) after auto-PBSCT. Complete remission (CR) was achieved
      in 16 cases (57%) and partial remission (PR) in 9 cases (32%), after auto-PBSCT
      The final responses after IF-RT were CR in 20 cases (71%) and PR in 5 cases
      (18%). Overall survival of cases with 2 cycles of CHOP-V regimen was 56% after a
      median observation time of 30 months, compared with 82% in cases with 3 cycles (p
      = 0.0732). The results suggested that the reduction of tumor size with the
      initial CHOP-V treatment was most important. In all cases, progression-free
      survival was 64% and the overall survival was 74% after a median observation time
      of 30 months, which showed a good outcome compared with that of HI- and H-risk
      group defined by the age-adjusted international prognostic index reported by
      Shipp et al.

PMID- 16444969
TI  - [Successful treatment of refractory mantle cell lymphoma with irinotecan].
AB  - A 59-year-old man presented in January 2003 with generalized lymphadenopathy. An
      inguinal lymph node biopsy showed mantle cell lymphoma (MCL). After four courses
      of Rituximab-CHOP therapy were administered, complete response (CR) was achieved.
      However, in August 2003, he presented with neck lymphadenopathy and was found to
      have relapsed. Several salvage therapies (ESHAP, Hyper-CVAD/MTX-ara-C) were
      administered, but CR was not achieved. After two courses of single-agent
      chemotherapy with CPT-11 (40 mg/m2) were administered on days 1, 2, 3, 8, 9, and
      10, CR was achieved. Several studies reveal that the long-term prognosis for MCL
      with conventional therapy is poor. This report describes CPT-11 therapy for MCL
      and provides evidence that CPT-11 is another therapeutic option in refractory
      cases of MCL.

PMID- 16444970
TI  - [Successful treatment with oral ribavirin of adenovirus-associated hemophagocytic
      syndrome in a stem cell transplantation recipient].
AB  - A 51-year-old woman with severe aplastic anemia underwent allogeneic peripheral
      blood stem cell transplantation using blood stem cells from an HLA-identical
      sibling. Adenovirus type 11 hemorrhagic cystitis developed and progressed to
      nephritis and hemophagocytic syndrome. Oral ribavirin was effective not only for
      the hemorrhagic cystitis and nephritis but also for the hemophagocytic syndrome.
      Since therapeutic strategies for adenovirus infection after hematopoietic stem
      cell transplantation have not been established, we present our case and discuss
      the therapeutic approach.

PMID- 16444971
TI  - [Renal insufficiency caused by leukemic cell infiltration in Sezary syndrome].
AB  - A 77-year-old woman was admitted to our hospital because of pneumonia and heart
      failure in July 2002. She had been diagnosed as having with Sezary syndrome in
      1993, and had been treated with a combination of prednisolone, methotrexate, and
      cyclosporin A with subsequent stable disease but persistent generalized
      erythroderma. On admission, the white blood count was 23.9 X 10(9)/L with 28%
      Sezary cells, and serum creatinine levels were within normal limits. One month
      after admission, the pneumonia and heart failure improved remarkably with
      antibiotics and diuretics. However, at the same time, her renal function
      deteriorated with increasingly high serum creatinine levels. She died of anuria
      in September, 2002. An autopsy showed marked perivascular and peritubular
      infiltration of abnormal lymphocytes with degenerative nephrotubuli in the
      kidneys. This patient may be the first reported case of Sezary syndrome with
      renal failure caused by leukemic infiltration.

PMID- 16444972
TI  - [Myelodysplastic syndrome with der (1;7) transformed from aplastic anemia 42
      years after onset].
AB  - A 51-year-old man had been diagnosed with severe aplastic anemia (AA) at the age
      of 9 years. He was treated with occasional transfusions for the next 35 years.
      Following initiation of cyclosporin A (CsA), the patient became transfusion
      independent at 44-years-old. Anemia improved after cessation of CsA and no
      therapy was required for the next 5 years. However, severe pancytopenia suddenly
      developed at the age of 51. Bone marrow aspiration revealed myelodysplastic
      syndrome (MDS) with der (1;7). The ineffectiveness of CsA for MDS led to resumed
      dependence on transfusion. This case suggests that the appearance of MDS clones
      might have contributed to transient hematological improvement. Bone marrow
      aspiration should be considered in patients with AA if unexpected hematological
      improvement appears.

PMID- 16444973
TI  - [Protease inhibitors].

PMID- 16444974
TI  - [Quantitative detection of Vibrio vulnificus in seafood].
AB  - To quantify the number of Vibrio vulnificus in shellfish, we compared the most
      probable number (MPN) combined with a culture (MPN-culture) or polymerase-chain
      reaction (PCR) assay (MPN-PCR) to a quantitative PCR assay. Enrichment in
      alkaline peptone water by MPN was conducted at 25 and 35 degrees C. Enrichment at
      35 degrees C was superior or similar to enrichment at 25 degrees C in over 65% of
      samples by MPNculture and in more than 75% of samples by MPN-PCR assay. V.
      vulnificus was more easily isolated on chromogenic agar medium during culture,
      MPN-PCR assay was superior or similar to MPNculture in over 90% of samples by
      enrichment at 25 degrees C and to over 88% of samples by enrichment at 35 degrees
      C. The number of V. vulnificus by quantitative PCR assay was similar to that of
      MPN-PCR assay in 6 of 8 samples but not from MPNculture. V. vulnificus
      contamination was frequently detected in samples from Kyushu Island.

PMID- 16444975
TI  - [Usefulness of interferon-gamma-based diagnosis of Mycobacterium tuberculosis
      infection in childhood tuberculosis].
AB  - We studied the usefulness of interferon-gamma measurement reagent QuantiFERON-TB
      2 G (QFT-2G), used to diagnose tubercle bacilli infections, as an indicator both
      for diagnosing primary tuberculosis (PTB) and for assessing therapeutic amorg
      pediatric Tuberculosis Outpatent cases effectiveness. Five cases showing typical
      PTB findings, such as cavitation, swollen lymph nodes, and nodular shadows at the
      pulmonary hilum, and diagnosed as tubercle bacillus infections, all showed
      positive reactions to QFT-2G, and in 3 asymptomatic cases without abnormalities
      detected in diagnostic imaging but QFT-2G-positive, one developed tuberculosis
      (TB) later. Among 12 patients who gave negative reactions to QFT-2G at their
      first visit and during observation from 6 months to 1 year, no TB occurrences was
      seen. Patients who were vaccinated for BCG and were tuberculin-positive showed
      negative reactions to QFT-2G, confirming that QFT-2G is not affected by BCG. One
      case of nontuberculous acid-fast bacilli in which Mycobacterium avium was
      detected was QFT-2G-negative. In 1 case, QFT-2G decreased as the patient's
      conditiorl improved. Without being influenced by BCG vaccination, QFT-2G
      demonstrated its usefulness in primary TB cases both for diagnosis and for
      assessing treatment effectiveness. Our results strougly suggested that QFT-2G is
      a potentially powerful tool with wide applications in diagnosis and assessment of
      treatment effectiveness in primary TB, even when bacterial elimination is low and
      diagnosis is difficult.

PMID- 16444976
TI  - [Usefulness of parenteral colistin in treating of lower respiratory infection due
      to multidrug-resistant Pseudomonas aeruginosa].
AB  - We report a case of cystic fibrosis in a 19-year-old woman who suffered from
      frequent exacerbations of lower respiratory infection due to multidrug-resistant
      Pseudomonas aeruginosa and who was successfully treated with parenteral colistin.
      Multidrug-resistant Pseudomonas aeruginosa isolated from sputum had become
      resistant to all parenteral antibiotics commercially available in Japan. She did
      not show clinical improvement despite treatment with several different
      combinations of available antibiotics. We therefore obtained parenteral colistin
      from a pharmacy outside Japan. She responded well to parenteral colistin without
      apparent side effects such as serious nephrotoxicity or neurotoxicity. Colistin
      is therefore an important alternative antibiotic for treating multidrug-resistant
      Pseudomonas aeruginosa and its use should be considered in severe infection. We
      hope that parenteral colistin will become available in Japan in the near future.

PMID- 16444977
TI  - [Two cases of pulmonary aspergillosis successfully treated with combinated
      micafungin and itraconazole therapy].
AB  - We report 2 cases of pulmonary aspergillosis treated successfully by combining
      micafungin and traconazole. Case 1: A 51-year-old man with hemoptysis and dyspnea
      on effort treated for pulmonary tuberculosis and aspergillosis was found on chest
      CT on admission to have a fungus ball in the left upper lobe and increasing
      consolidation around the cavity of both lung fields. Bronchoscopy proved positive
      for aspergillus PCR in bronchial lavage. He was diagnosed with chronic
      necrotizing pulmonary aspergillosis, based on clinical and radiological findings
      and the positive reaction for aspergillus PCR. He was treated with micafungin
      alone at first, this proved ineffective, so itraconazole was added, resulting in
      improvement. Case 2: A 24-year-old woman with stabilized Hodgkin's disease
      (mixed). She had suffered from a cough and back pain, and chest CT showed
      increasing consolidation inside and around a giant bulla. She was diagnosed with
      chronic necrotizing pulmonary aspergillosis, based on isolation for Aspergillus
      sp. in sputum culture and a positive reaction for Aspergillus antigen in
      bronchial lavage and Aspergillus antibody in serum. She was treated with the
      combined micafungin and itraconazole, which rapidly improved symptoms and
      radiological findings. Pulmonary aspergillosis therapy is often difficult,
      because delivery of the drug to the infection site is limited and drug tolerance
      is poor. We found that combination micafungin and itraconazole therapy is
      tolerable and effective in these cases.

PMID- 16444978
TI  - [Autopsy case of pulmonary aspergillosis soon after convalescence from pulmonary
      tuberculosis].
AB  - A 70-year-old man with liver cirrhosis and previous gastrectomy admitted for
      fever, coughing, and bloody sputum soon after convalescing from pulmonary
      tuberculosis had a peripheral white blood cell count of 9,900/microL, C-reactive
      protein of 14.1mg/dL, serum albumin of 2.0g/dL, and serum positive for
      antiaspergillus and beta-D glucan antibodies. Chest radiography showed thickening
      of the walls of the large residual cavities with previous tuberculosis lesions
      and infiltrates around them. On day 2 of hospitalization, Aspergillus fumigatus
      without other bacillus was detected in sputum culture taken on admission. Despite
      immediate treatment with intravenous micafungin and oral itraconazole and
      improved brief initial improvement, his general condition abruptly deteriorated
      into frequent massive hemoptysis and he developed of shock, respiratory failure,
      and severe malnutrition, dying 30 days later. Autopsy findings showed pulmonary
      aspergillosis in and around the large cavities and on the other side of the
      lungs. Pulmonary aspergillosis without hematological malignanciy and
      immunosuppression can thus be abruptly severe and fatal due to malnourishment
      stemming from pre-existing conditions such as chronic hepatitis despite prompt,
      ordinarily adequate medical treatment.

PMID- 16444979
TI  - [Roles of immunity in the pathology of inflammatory bowed disease].

PMID- 16444980
TI  - [Molecular mechanisms of oxidative stress response and implications in diseases].

PMID- 16444981
TI  - [Superoxide anion and reactive oxygen species and redox regulation in the liver].

PMID- 16444982
TI  - [A case of alcoholic liver cirrhosis with pyogenic spondlitis and iliopsoas
      abscess].

PMID- 16444983
TI  - [A case of diffuse gastritis and duodenitis associated with ulcerative colitis].

PMID- 16444984
TI  - [A case of intrahepatic bile duct adenoma].

PMID- 16444985
TI  - [A case of mucin-producing cystic duct cancer protruding into the common bile
      duct].

PMID- 16444986
TI  - [A case of resected pancreatic metastasis from renal cell carcinoma 26 years
      after right nephrectomy].

PMID- 16444987
TI  - [A case report of autoimmune pancreatitis with abnormal elevation of CA19-9 and
      patholocal findings].

PMID- 16444988
TI  - Depiction of residual emboli following pulmonary embolism with thrombotic
      scintigraphy.
AB  - BACKGROUND: In the treatment of pulmonary embolism (PE), the presence of residual
      emboli is known to seriously affect the recurrence and prognosis. We attempted to
      depict the residual emboli in the subacute stage of PE using indium-111-oxine
      labeled platelet scintigraphy (In-plt). METHODS: In-plt was performed on 22
      patients with PE who showed an improvement according to lung perfusion
      scintigraphy. Their accumulation was assessed along with the blood coagulation
      ability measured on the same day. In addition, radioisotope venography (RI-veno)
      was performed simultaneously with In-plt to measure the circulatory findings in
      the lower limb for comparison. All patients received systemic heparin during the
      acute stage and received warfarin at the time of testing. RESULTS: Accumulation
      of In-pit was observed in 7 patients (32%), and positive signals were found in
      the lower limbs or pelvic cavity in all cases. Two patients were suspected of
      having poor lower limb circulation from their RI-veno findings, and these
      findings were largely consistent with the areas of In-plt accumulation.
      DISCUSSION: Some emboli persist after extensive anti-coagulation therapy. The use
      of In-pit is effective in determining the therapeutic measures and assessing the
      prognosis as this method allows us to clearly depict the existence of such
      emboli.

PMID- 16444989
TI  - The relationship between coronary artery calcification detected by non-gated
      multi-detector CT in patients with suspected ischemic heart disease and
      myocardial ischemia detected by thallium exercise stress testing.
AB  - OBJECTIVE: To examine whether we could predict myocardial ischemia when coronary
      artery calcification is detected by non-gated multidetector CT in patients with
      suspected ischemic heart disease. METHODS: Eighty-three patients suspected of
      having ischemic heart disease (55 men, 28 women; age range 36-83 years; mean age
      68 years) underwent multidetector CT and T1-201 single photon emission computed
      tomography. Prediction of myocardial ischemia by coronary arterial calcification
      detected on CT was evaluated by comparing the coronary artery territories that
      showed calcification with the area of myocardial ischemia determined by SPECT.
      The sensitivity, specificity, positive predictive value, and negative predictive
      value of multidetector CT for predicting myocardial ischemia were calculated.
      Coronary angiography was also examined and compared with multidetector CT. Risk
      factors, including hypertension, smoking, hyperlipidemia, diabetes, and family
      history, were compared for evidence of coronary artery calcification detected by
      multidetector CT and myocardial ischemia detected by thallium nuclear scans.
      RESULTS: For analysis by patients, the sensitivity, specificity, positive
      predictive value, and negative predictive value of coronary artery calcification
      for myocardial ischemia detection were 65, 63, 56, and 71%, respectively.
      Similarly, for analysis by coronary arterial territories, those values were 56,
      77, 41 and 86%, respectively. Coronary stenosis on CAG was also related to the
      ischemia determined by SPECT and calcification on multidetector CT. Ischemia was
      better influenced by risk factors than was coronary arterial calcification.
      CONCLUSIONS: For analysis by coronary arterial territories, the specificity and
      negative predictive value of coronary arterial calcification seen by
      multidetector CT are relatively high.

PMID- 16444990
TI  - Distinct different intra-tumor distribution of FDG between early phase and late
      phase in mouse fibrosarcoma.
AB  - An early image of intra-tumor distribution of 14C-labeled fluorodeoxy glucose
      (14C-FDG) was compared with a late image of 18F-labeled FDG (18F-FDG) using mouse
      fibrosarcoma. Heterogeneous intra-tumor distribution of 14C-FDG was observed 1
      minute post injection of the tracer, whereas relatively homogeneous distribution
      of 18F-FDG was seen 30 minutes later. 14C-FDG was particularly taken up in the
      peripheral part of the tumor immediately after the tracer injection. A gradual
      and significant increase in 18F-FDG accumulation with time was seen in the
      central part of tumor, which indicated an enhancement of anaerobic glycolysis. An
      initial uptake of 18F-FDG was also compared with distribution of 14C
      iodoantipyrine and 14C-thymidine uptake. Intratumoral distribution of initial
      uptake of 18F-FDG showed almost the same regional distribution of 14C
      iodoantipyrine. A similar distribution of 14C-thymidine as the initial uptake of
      18F-FDG was also observed. These results indicated that a high initial FDG uptake
      area seemed to be highly proliferative. A significant difference in the
      intratumoral distribution of FDG between early phase and late phase seemed to be
      related to heterogeneous biological characteristics of tumor cells.

PMID- 16444991
TI  - PET evaluation of fatty tumors in the extremity: possibility of using the
      standardized uptake value (SUV) to differentiate benign tumors from liposarcoma.
AB  - OBJECTIVE: The relative utility of various preoperative diagnostic imaging
      modalities, including PET (utilizing FDG and FMT), CT, and MR imaging, for
      evaluation of lipoma and liposarcoma, especially well-differentiated liposarcoma,
      was investigated. METHODS: Imaging findings in 32 patients with
      histopathologically documented lipoma, including one with fibrolipoma and one
      with angiolipoma, and 25 patients with liposarcomas whose subtypes included 10
      well-differentiated, 10 myxoid, and 5 other types were reviewed retrospectively.
      Pre-operative imaging included FDG-PET (n = 44), FMT-PET (n = 21), CT (n = 25),
      and MR imaging (n = 53). RESULTS: Statistically significant imaging features of
      MR images favoring a diagnosis of liposarcoma involved lesions containing less
      than 75% fat (p < 0.001) as well as the presence of septa (p < 0.001). As
      compared with well-differentiated liposarcoma, benign lesions were differentiated
      significantly only by the presence of septa (p < 0.001), which also provided
      significant differentiation on CT (p < 0.05). The mean SUVs for malignant tumors
      were significantly higher than those for benign lesions in both FDG- and FMT-PET
      analyses (p < 0.0001, p = 0.0011, respectively). By using a cut-off value for FDG
      and FMT-PET set at 0.81 and 1.0 respectively, which provided the highest
      accuracy, benign lesions were differentiated significantly from liposarcomas (p <
      0.001, and p < 0.02). Furthermore, benign tumors and the three subtypes of
      liposarcoma were divided significantly into four biological grades by FDG- and
      FMT-accumulation rates (rho = 0.793, p < 0.0001; and rho = 0.745, p = 0.0009,
      respectively). A cut-off value of 0.81 for FDG-PET provided significant
      differentiation between benign lesions and well-differentiated liposarcoma (p <
      0.01). CONCLUSIONS: The presence of septa on MR images differentiated lipomas
      from liposarcoma, even well-differentiated type. PET analysis, especially FDG
      PET, quantitatively provided not only the differentiation but also the metabolic
      separation among subtypes of liposarcoma. Interpretation of the visual diagnostic
      modalities requires extensive experience and carries a risk of ignoring a
      critical portion of malignancy. PET metabolic imaging may be an objective and
      useful modality for evaluating adipose tissue tumors preoperatively.

PMID- 16444992
TI  - Sentinel lymphoscintigraphy in patients with breast cancer undergoing excisional
      biopsy.
AB  - Some small tumors of the breast cannot be diagnosed by needle biopsy, and an
      excisional biopsy is occasionally needed for the diagnosis. Sentinel node
      navigation surgery is frequently suitable for patients with such small breast
      cancers. The purpose of this study was to compare sentinel lymphoscintigrams in
      breast cancer patients who had previously undergone excisional biopsy with
      sentinel lymphoscintigrams in patients undergoing no excisional biopsy. We also
      investigated the possibility of clinical application of the sentinel node
      navigation procedure in the former group of patients. METHODS: Sentinel
      lymphoscintigrams of 43 patients with breast cancer undergoing excisional biopsy
      were compared to those of 116 patients without excisional biopsy.
      Lymphoscintigrams were obtained by using intradermal and/or subdermal injections
      of technetium-99m labeled phytate at 2 points on each side of the dermal incision
      in patients after excisional biopsy. Injections were performed at 2 points of the
      skin over the tumor in the patients who had not undergone excisional biopsy.
      RESULTS: Axillary lymph nodes were visualized in 42 of 43 patients undergoing
      excisional biopsy (98%) and in 115 of 116 patients without excisional biopsy
      (99%). The number of visualized axillary nodes was 1 to 5 (mean +/- SD = 2.1 +/-
      1.0) and 1 to 5 (mean +/- SD = 1.9 +/- 1.0) in the two groups, respectively. No
      significant difference was determined between the two groups. Parasternal lymph
      nodes were depicted in 3 patients after excisional biopsy who had the tumor in
      the outer half of the breast, in contrast to 4 without excisional biopsy who had
      the tumor in the inner half. Intramammary hot spots were observed in 5 patients
      after excisional biopsy and in 2 without excisional biopsy. Lymphatic vessels
      were observed in 23 patients (53%) who had the excisional biopsy, and in 37 (32%)
      who did not have the biopsy. The former figure was significantly higher than the
      latter (p < 0.02). CONCLUSION: Sentinel node navigation surgery for axillary
      nodes was shown to be possible in patients undergoing excisional biopsy. However,
      the visualization of parasternal nodes, intramammary hot spots and lymphatic
      vessels tended to increase in number, and care must be exercised in the
      management of these patients.

PMID- 16444993
TI  - Correlation of amino-acid uptake using methionine PET and histological
      classifications in various gliomas.
AB  - OBJECTIVE: The uptake of L-methyl-11C-methionine (MET) by gliomas is greater than
      that by intact tissue, making methionine very useful for evaluation of tumor
      extent. If the degree of malignancy of brain tumors can be evaluated by MET-PET,
      the usefulness of MET-PET as a means of diagnosing brain tumors will increase.
      METHODS: We performed this study on 67 glioma patients between 3 and 69 years of
      age (36 males and 31 females). Tumors included diffuse astrocytoma, anaplastic
      astrocytoma, glioblastoma, ependymoma, oligodendroglioma, medulloblastoma,
      dysembryoplastic neuroepithelial tumor, choroid plexus papilloma, central
      neurocytoma, optic glioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma,
      and ganglioglioma. Tumor activity and degree of malignancy were evaluated using
      Ki-67LI (LI: labeling index) and Kaplan-Meier survival curves. The correlations
      between methionine uptake and tumor proliferation (tumor versus contralateral
      gray matter ratio (T/N) and Ki-67LI) were determined for the group of all
      subjects. The existence of significant correlations between T/N and Ki-67LI and
      between SUV and Ki-67LI was determined for astrocytic tumors. Receiver operating
      characteristics (ROC) analysis of T/N and standardized uptake value (SUV) was
      performed for the group of astrocytic tumors. We also determined the ROC cut-off
      levels to ensure high accuracy of the analysis. RESULTS: For the 67 cases of
      glioma, the degree of accumulation was variable. Ki-67LI differed significantly
      between the high-grade group and low-grade group at T/N levels between 1.5 and
      1.8 on analysis using tumor proliferative potential (p = 0.019-0.031). The
      prognosis differed significantly between the high-grade and low-grade groups when
      T/N was in the range of 1.6-1.8 (p = 0.028-0.032). The accuracy thus calculated
      was highest (85.7%) when T/N was 1.5 as determined by ROC analysis. CONCLUSIONS:
      When analysis was confined to cases of astrocytic tumor, a correlation was noted
      between methionine accumulation and Ki-67LI. For the astrocytic tumors, T/N ratio
      seemed to be more useful as a diagnostic indicator than SUV. The cut-off level of
      T/N ratio for distinction between high-grade and low-grade astrocytoma appears to
      lie between 1.5 and 1.6.

PMID- 16444994
TI  - Evaluation of tumor FDG transport and metabolism in primary central nervous
      system lymphoma using [18F]fluorodeoxyglucose (FDG) positron emission tomography
      (PET) kinetic analysis.
AB  - OBJECTIVE: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET) has been used as a promising tool to diagnose primary central nervous
      system lymphoma (PCNSL) because the tumor shows very high FDG accumulation, no
      data exist evaluating the extent of tumor FDG transport and metabolism. The aim
      of this study was to evaluate the feasibility of FDG-PET kinetic analysis in
      measurement of uptake parameters of FDG in the lymphoma tissues and in the
      assessment of treatment effects in patients with PCNSL. METHODS: Dynamic FDG-PET
      examination was performed in 7 histologically proven PCNSL patients before and
      after methotrexate-based chemotherapy. RESULTS: Before the chemotherapy, the
      highest CMRglc in the tumor for all 7 patients was 79.4 +/- 27.2 micromol/100
      g/min. This value was significantly higher than that observed in the normal
      cortex in 14 control patients (44.3 +/- 6.0 micromol/100 g/min, p < 0.001). The
      phosphorylation (k3) activity was also significantly higher in the tumor (0.093
      +/- 0.026 min(-1)) compared with the normal cortex (0.064 +/- 0.014 min(-1), p <
      0.05). On the other hand, the transporter (K1) activity in the tumor (0.079 +/-
      0.016 ml/min) was similar to that observed in the normal cortex (0.082 +/- 0.012
      ml/min). The chemotherapy significantly reduced the volume of the tumor in 6 of 7
      patients and the highest CMRglc in the tumor examined 18.0 +/- 5.5 days after the
      chemotherapy (34.0 +/- 21.8 micromol/100 g/min) was significantly lower than that
      observed before the chemotherapy (p < 0.01). This reduction in FDG uptake was
      concomitant with a significant reduction in both the K1 and k3 values (p < 0.05).
      The reduction in the k3 value after the chemotherapy was marked in 6 of 7
      patients in whom the tumor responded to the first chemotherapy. CONCLUSIONS:
      Dynamic image acquisition can separate regional FDG uptake into FDG transport and
      phosphorylation activity in the lymphoma tissues. Tumor FDG uptake was
      significantly higher with accelerated phosphorylation activity compared with that
      observed in the normal cortex.

PMID- 16444995
TI  - The impact of FDG-PET in the management of patients with salivary gland
      malignancy.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of FDG-PET in the
      management of patients with salivary gland malignancy. PATIENTS AND METHODS: We
      performed 45 FDG PET studies in 31 patients with salivary malignant tumors, using
      PET (33 studies) and PET/CT (12 studies). Patients comprised 21 males and 10
      females with a mean age of 69 y (range 38-89). Nineteen patients had a single
      study, ten patients had 2 and two patients had 3 studies. Twelve studies were
      performed for initial staging and 33 studies for restaging. Four patients of the
      initial staging group were restaged with PET after therapy. Histology consisted
      of 8 adenocarcinomas, 8 squamous cell carcinomas, 4 adenoid cystic carcinomas, 4
      carcinoma ex pleomorphic adenomas, 2 mucoepidermoid carcinomas, 2 poorly
      differentiated carcinomas, 1 salivary duct carcinoma, 1 lymphoepithelial
      carcinoma and 1 melanoma. PET findings were reviewed with the clinical and
      radiologic findings and the impact of PET on staging and patient management was
      determined. RESULTS: In the initial staging group, all 12 primary lesions (100%)
      showed positive FDG uptake (5 squamous cell carcinomas, 2 adenocarcinomas, 2
      poorly differentiated carcinomas, 1 carcinoma ex pleomorphic adenoma, 1 salivary
      duct carcinoma, 1 lymphoepithelial carcinoma). Three patients (25%) had FDG
      positive distant disease (liver, bone, lymph nodes); surgery was canceled and
      therapy changed to chemoradiation. One patient (9%) with no FDG uptake in the
      neck nodes avoided a planned neck dissection. In the restaging group (33 studies
      in 23 patients), 5 patients (22%) had FDG positive distant disease, which changed
      the treatment from surgery to chemoradiation or other. A second primary lesion
      was detected in one patient (4%). One patient (4%) with clinically suspected
      recurrence was able to avoid other invasive procedures because of the negative
      PET. Overall, FDG PET resulted in a major change in management in 11 of 31
      patients (35%). CONCLUSION: This study shows that FDG PET has a significant
      impact on the management of patients with salivary malignant tumors in both the
      initial staging and restaging.

PMID- 16444996
TI  - The relationship between bone mineral density and immobilization duration in
      hemiplegic limbs.
AB  - OBJECTIVE: Prolonged immobilization in stroke is known to result in
      hypercalciuria, hypercalcemia, accelerated bone resorption, and osteoporosis.
      Furthermore, bone mineral loss accelerated with increasing duration of
      hemiplegia. Although stroke is a common disease that causes sudden
      immobilization, relatively few investigations of bone metabolism in stroke have
      been reported. The aim of this study was to investigate the changes in bone
      mineral density of the forearms and legs related to duration of hemiplegia
      induced immobilization after stroke. METHODS: Forty-one hemiplegic patients with
      stroke were evaluated. The patients' age, gender and duration of hemiplegia
      induced immobilization were recorded. The measurements of bone mineral density
      (BMD) in all patients were evaluated with DEXA using the Norland apparatus. The
      BMD values (g/cm2) were determined by measurements made in the lumbar vertebrae,
      both forearm and legs (femoral neck and trochanter). RESULTS: We found that bone
      mineral density was decreased in the affected extremities relative to the intact
      contralateral side on measurements by dual energy x-ray absorptiometry in bones
      such as forearm, femoral neck and trochanter. There was a significant difference
      between bone mineral density of paretic and nonparetic forearms and legs. Bone
      mineral density of the upper limbs was lower than that of the lower limbs. There
      was a negative correlation between duration of hemiplegia and BMD values.
      CONCLUSIONS: Bone mineral loss may be related to the duration of hemiplegia
      induced immobilization. Bone mineral loss is accelerated when the duration of
      hemiplegia is prolonged.

PMID- 16444997
TI  - Evaluation of [11C]SA5845 and [11C]SA4503 for imaging of sigma receptors in
      tumors by animal PET.
AB  - Sigma receptors are expressed in a wide variety of tumor cell lines, and are
      expressed in proliferating cells. A radioligand for the visualization of sigma
      receptors could be useful for selective detection of primary tumors and their
      metastases, and for non-invasive assessment of tumor proliferative status. To
      this end we evaluated two sigma receptor ligands, [11C]SA5845 and [11C]SA4503. In
      an in vitro study, AH109A hepatoma showed moderate densities of sigma1 and sigma2
      receptors, and VX-2 carcinoma showed a high density of sigma2 receptors: Bmax
      (fmol/mg protein) for sigma1 vs. sigma2, 1,700 vs. 1,200 for AH109A hepatoma and
      800 vs. 10,000 for VX-2 carcinoma. In a cell growth assay in vitro, neither
      SA5845 nor SA4503 (<10 microM) showed any inhibitory effect on proliferation of
      the AH109A hepatoma cells. In rats, the uptake of [11C]SA5845 and [11C]SA4503 in
      AH109A tissues was accumulated over the first 60 minutes; however, the uptake of
      both tracers increased by co-injection with haloperidol as a sigma receptor
      ligand. On the other hand, in the PET studies of rabbits, the uptake of
      [11C]SA5845 in the VX-2 carcinoma was relatively higher than that of [11C]SA4503,
      because of a much higher density of sigma2 receptors compared to sigma1 receptors
      in the VX-2 tissue, and the uptake of both tracers in the VX-2 tissue was
      decreased by carrier-loading and pre-treatment with haloperidol ([11C]SA5845, 53%
      and 26%, respectively; [11C]SA4503, 41% and 22%, respectively at 30 minutes after
      injection). Therefore, [11C]SA5845 and [11C]SA4503 may be potential ligands for
      PET imaging of sigma receptor-rich tumors.

PMID- 16444998
TI  - Comparison of myocardial blood flow induced by adenosine triphosphate and
      dipyridamole in patients with coronary artery disease.
AB  - Myocardial perfusion imaging with adenosine triphosphate (ATP) has been used
      increasingly to diagnose coronary artery disease (CAD) and assess risk for this
      disease. This study compared absolute myocardial blood flow (MBF) and myocardial
      flow reserve index (MFR) with ATP and dipyridamole (DIP) in patients with CAD.
      MBF was quantified by 15O-H2O PET in 21 patients with CAD (17 male, 4 female),
      aged 55 to 81 years. MBF was measured at rest, during intravenous injection of
      ATP (0.16 mg/kg/min), and again after DIP infusion (0.56 mg/kg). Regions of
      interest were drawn in nonischemic and ischemic segments based on findings from
      thallium-201 (201T1) scintigraphy and coronary angiography (CAG). Absolute MBF
      values and indexes of MFR were calculated in nonischemic and ischemic segments.
      Intravenous injection of ATP and DIP significantly increased MBF in nonischemic
      (2.4 +/- 0.9 and 2.1 +/- 0.8 ml/g/min, respectively; p < 0.01, for both) and in
      ischemic segments (1.3 +/- 0.4 and 1.5 +/- 0.4 ml/g/min, respectively; p < 0.01,
      for both). There was a significant difference in MBF values between ATP and DIP
      in nonischemic segments (p < 0.05), which was not observed in ischemic segments.
      In nonischemic segments, ATP produced higher MFR than DIP (2.1 +/- 0.8 and 1.8 +/
      0.7, respectively; p < 0.05), while no significant difference was observed in
      ischemic segments (1.5 +/- 0.6 and 1.7 +/- 0.3, respectively). ATP produced a
      greater hyperemia than DIP between the ischemic and nonischemic myocardium in
      patients with CAD. ATP is as effective as DIP for the diagnosis of CAD.

PMID- 16444999
TI  - Oblique view of preoperative lymphoscintigraphy improves detection of sentinel
      lymph nodes in esophageal cancer.
AB  - Because sentinel lymph nodes (SLNs) of esophageal cancer can be widely located
      between the neck and the upper abdomen, lymphoscintigraphy plays an important
      role in their detection, but some modifications are required to clearly visualize
      their locations. Recently, we applied the stereoscopic imaging method by adding
      the 10-degree oblique view to the conventional lymphoscintigraphy for SLNs, so
      that we could better determine SLN locations on the basis of depth information.
      In this report, we describe a case in which the oblique view of the
      lymphoscintigram contributed to improving the visualization of a mediastinal SLN
      of esophageal cancer. Evaluation of the patient's chest CT image validated the
      notion that gamma rays from SLN are less absorbed by the surrounding soft tissues
      and the sternum in acquisition from the oblique view than from the true anterior
      view. The additional oblique view of the lymphoscintigram is useful for
      evaluation of the SLNs of esophageal cancer.

PMID- 16445000
TI  - Usefulness of FDG-PET imaging for the radiotherapy treatment planning of
      pyothorax-associated lymphoma.
AB  - Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the
      pleural cavity after a long-standing history of chronic pyothorax (CP). F-18
      fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is a useful
      modality for determination of disease extent of various malignant tumors,
      including malignant lymphoma, but there have been no reports describing the
      usefulness of FDG-PET imaging in PAL. Here we report a case of PAL that relapsed
      after chemotherapy and was successfully treated by radiotherapy. FDG-PET imaging
      revealed that the tumor was localized to a soft-tissue attenuation mass behind
      the CP cavity in the right thorax, but did not infiltrate the CP cavity. A total
      dose of 40 Gy was administered to the area that included the PET-positive lesion,
      instead of including the entire CP cavity in the radiation field. Although
      computed tomography (CT) showed a residual mass, no FDG uptake was indicated by
      FDG-PET imaging performed just after the end of radiotherapy, and additional
      irradiation was not performed. No sign of relapse was found by FDG-PET imaging 3
      months later. FDG-PET imaging was useful for both the planning of radiotherapy
      and assessing the treatment response of PAL.

PMID- 16445001
TI  - Extraskeletal osteosarcoma: extensive tumor thrombus on fused PET-CT images.
AB  - A 30-year-old woman developed extraskeletal osteosarcoma in the right buttock and
      thigh. Radiographs and unenhanced computed tomography (CT) showed a large,
      multilobulated mass accompanied by mineralized matrix. Contrast-enhanced CT and
      magnetic resonance (MR) images showed extensive tumor thrombus in the right
      internal- and external iliac veins. Co-registered positron emission tomography
      (PET) and CT images showed abnormal F-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake
      in the tumor thrombus. PET study in our patient provided information concerning
      disease extent and viability of tumor thrombus.

PMID- 16445002
TI  - Tc-99m(V)-DMSA in wound infection after closure of an ileostomy.
AB  - We present a 71-year-old man who underwent closure of an ileostomy and had a
      fever seven days post surgery. Both Tc-99m(V)-dimercaptosuccinic acid (DMSA) and
      gallium-67 citrate scans showed increased tracer accumulation in the right lower
      quadrant of the abdomen. Tc-99m(V)-DMSA scintigraphy can be a rapid alternative
      tool in the detection of wound infection in patients after ileostomy closure.

PMID- 16445003
TI  - The incidence of recurrence and hypothyroidism after radioiodine treatment in
      patients with hyperthyroidism in Trakya, a mild iodine deficiency area, during
      the period 1991-2003.
AB  - OBJECTIVE: The purpose of this retrospective study was to evaluate the incidence
      of recurrence and the success of radioiodine treatment (RIT) in the Trakya region
      of Turkey, an area with mild iodine deficiency, and to compare the effect of dose
      regimen selection (fixed (FD) or calculated dose (CD)) on treatment success.
      MATERIAL AND METHODS: The study sample included 148 patients (40 male, median age
      50) treated with radioiodine between the years 1991-2003. Patients were
      categorized into three diagnostic groups: Graves' disease (GD) (n = 65), solitary
      toxic adenoma (TA) (n = 29), and toxic multinodular hyperthyroidism (TMH) (n =
      54), and each divided into two subgroups according to treatment method; the first
      group was treated with a FD of 370 MBq (10 mCi), and the second with CD. RESULTS:
      The largest group was GD (44%), followed by TMH (36%). Median duration of follow
      up was 28 months (range 6-147). FD was given to 52.7% of all patients and CD was
      given to 47.3%. There was a partial difference in the dose regimen between all
      groups, but did not reach statistically significant levels (FD vs. CD: 65%-35%;
      38%-62%; 46%-54%; GD, TA, TMH respectively, p > 0.05). Total cure rate in FD and
      CD was 46 (59%) and 37 (52.9%), respectively. The rates of hypothyroidism for GD,
      TA, and TMH groups were 28 (43.1%), 6 (20.7%) and 16 (29.6%), respectively. The
      incidence of hypothyroidism did not vary significantly between any groups (p >
      0.05). At the end of the follow-up period, a total of 104 patients (70.3%) were
      treated successfully. There was no significant difference in the cure rate
      between any groups (p > 0.05). CONCLUSIONS: The treatment success in all groups
      and subgroups did not differ significantly between FD and CD. Our lower cure rate
      than in previous studies may be related to iodine deficiency. Higher doses of
      radioiodine may be required to increase final treatment success in endemic goiter
      areas. If this true, dosimetry and calculated dose regimen would be required in
      all groups of patients instead of an FD concept. However, our findings should be
      verified in larger series of patients, with longer follow-up period, and urinary
      iodine concentration measurements.

PMID- 16445004
TI  - [Influence of tendencies toward depression, neurosis and psychosomatic disorders
      on oral symptoms].
AB  - This study revealed that the tendencies towards depression, neurosis, and
      psychosomatic disorders have effects on oral symptoms. The total number of
      subjects was 102. The subjects were divided into two groups using the SDS (Self
      rating Depression Scale): a control group of 66 subjects with an SDS value of
      less than 40, and a group of 36 subjects having depression tendencies with an SDS
      value of over 50. Most of the subjects in the depression tendency group showed
      symptoms of neurosis and psychosomatic disorders as well. The two groups were
      compared on the basis of their psychological characteristics, dosages of medicine
      taken, esthesis of mouth dryness, glossalgia, salivary flow rate, oral
      wettability, existence of dental cavities, and condition of the oral mucosa. No
      xerostomia at the mucobuccal fold was observed in the depression tendency group.
      However, there was an evident decrease of the resting salivary flow rate and the
      wettability of proglossis. It is considered that such a decrease resulted in an
      increase in the symptoms derived from xerostomia or esthesis of mouth dryness.
      The number of conservable but untreated dental cavities in the depression
      tendency group was larger than that in the control group with a significant
      difference, suggesting that both oral self-care and dental care management tended
      to be inadequate in the depression tendency group.

PMID- 16445005
TI  - [Investigation for bone fixation effect of thin HA coated layer on Ti implants].
AB  - In 1995, the author reported the development of unique cementless total hip
      joints applying hydroxyapatite (HA) flame coating onto a porous titanium surface
      which is arc-sprayed with pure titanium material in argon gas at atmospheric
      pressure. The surface roughness of the porous layer was 360 microm Rmax, and the
      layer was more resistant to blast erosion than the conventional low pressure
      plasma sprayed porous layers. The thickness of the HA layer was between 20 and 40
      microns considering the balance of bone conduction effect of HA and the risk of
      mechanical detachment of the layers from the porous titanium. Short-term animal
      tests showed excellent results. At that time a specific question was raised as to
      whether or not the coated HA layers would remain in the living bone for a long
      time. The results obtained from observation of retrieved specimens show that the
      thickness of the HA coating layer is sufficient for new bone formation after
      implantation, and HA would be absorbed in the body within a few years, after
      contributing to the new bone formation.

PMID- 16445006
TI  - Curing behavior of a nanocomposite as a function of polymerization procedure.
AB  - The purpose of this study was to analyze the curing behavior of a nanocomposite
      by assessing in real time the degree of cure at depths of 2 mm and 6 mm. The
      variation of hardness with depth, shrinkage stress, and curing time until
      gelation with 16 curing regimes was further investigated using one halogen and
      three LED curing units. In the present study, it was shown that the soft-start
      polymerization concept is still valid, even with high-power LED curing units. A
      soft cure polymerization resulted in reduced shrinkage stress while
      simultaneously keeping the degree of cure and mechanical properties constant. For
      all tested curing unit types, a short polymerization duration (10 seconds) was
      insufficient to cure the nanocomposite in deeper layers--since the variation of
      hardness with depth showed a discontinuity between the layers, thus accounting
      for a decreased hardness of up to 30%.

PMID- 16445007
TI  - Novel bulk carbon nanotube materials for implant by spark plasma sintering.
AB  - Novel, bulk multiwall carbon nanotubes (MWCNTs) sintered with polycarbosilane
      (PCS) as a binder agent were fabricated by spark plasma sintering (SPS), and
      their microstructure and properties were investigated. Sintering was done with 20
      60 MPa pressure at 1200 degrees C. SEM and TEM observations showed that the
      nanosized tube microstructure was preserved even after sintering, and tubes
      adhered to each other with the nanosized nodules of SiC pyrolyzed form PCS as
      revealed by X-ray diffraction. Bulk density and Vickers hardness were found to
      increase, whereas the specific surface area decreased, as PCS content and
      sintering pressure increased. Through animal experiments, the inflammatory
      reaction of CNTs/PCS material was found to be slightly increased with increasing
      PCS content. In conclusion, sintered CNTs had physical and mechanical properties
      close to bone, and their good biocompatibility based on tissue response served to
      pave their way as a suitable implant material in the future.

PMID- 16445009
TI  - Water durability of resin bond to precious metal alloys using adhesive resins
      containing adhesion promoting monomers.
AB  - Adhesive resins for precious metals were prepared by adding an adhesion promoting
      monomer to MMA-PMMA/TBBO resin. Precious metal alloys bonded by the adhesive
      resin were thermocycled 0, 1,000, 2,000, or 4,000 times in water between 4 and 60
      degrees C, and tensile bond strengths were measured. Debonded metal surfaces
      after the tensile test were analyzed based on an area of cohesive failure. Three
      way ANOVA revealed that all the three parameters--adherend, adhesive monomer, and
      number of thermal cycles--exhibited a significant influence on bond strength.
      Bond strength significantly decreased with increasing number of thermal cycles
      except for resin with 9,10-epithiodecyl 4-vinylbenzoate (EP8VB) to Au alloy. Mean
      bond strength of adhesive resin with 9,10-epithiodecyl methacrylate (EP8MA),
      EP8VB, or 3,4-epithiobutyl 2,2-bis(methacryloyloxymethyl)propionate (EP2BMA)
      exceeded 22 MPa after 4,000 thermal cycles. Analysis of debonded surfaces
      revealed the applicability of EP8MA, EP8VB, and EP2BMA as an adhesive monomer
      component of adhesive resin formulations.

PMID- 16445008
TI  - Effect of texture of polishing particle on the surface roughness of a cobalt
      chromium alloy using a centrifugal shooting type polishing machine.
AB  - In a previous report, we investigated the influence of the shooting angle of
      polishing particle on the surface roughness of a cobalt-chromium (Co-Cr) alloy
      using a centrifugal shooting type polishing machine. In the present work, we
      examined the effects of the texture of polishing particle and polishing time on
      the surface roughness of Co-Cr alloy cast specimens. Nine different textures of
      polishing particle were investigated with respect to core material and particle
      abrasiveness: three different elastic body cores (core A, hard chloroprene
      rubber; core B, soft chloroprene rubber; core C, natural rubber) and three
      different green carborundum powders as abrasives (#800, #3000, and #6000).
      Polishing was performed under a fixed shooting angle of 30 degrees for six
      different polishing times (1, 2, 3, 5, 7, and 10 minutes). Surface roughness (Ra,
      Sm) and cutting depth on the polished surface were measured after each polishing
      stage. Surface roughness was significantly improved within three minutes,
      particularly using a polishing particle with rough carborundum powder (#800 or
      #3000) and a heavy core (core A or core B). Cutting depth increased in proportion
      to polishing time and roughness of carborundum powder, and was least with core C.
      These results suggested that a polishing particle composed of core B and #3000
      carborundum paste was superior for the intermediate polishing of a Co-Cr alloy,
      and that polishing time should be limited to within three minutes.

PMID- 16445010
TI  - Mechanism by which porous structure is formed on the surface of gold alloy
      containing only Cu as base metal.
AB  - Gold alloys with Cu contents of 10 mass%, 20%, and 30% were used for
      morphological observation of porous surface structures after heating at 800
      degrees C in air followed by pickling with acid solution. With increasing Cu
      content in the gold alloy, the internal oxidation zone became well-developed in
      the alloy matrix. The mechanism by which a porous structure was formed on the
      surface of a gold alloy containing only Cu as a base metal was thought to be as
      follows: Cu2O which formed along the grain boundaries acted as a diffusion path,
      permitting the penetration of O2- into the inner alloy matrix, and thereby
      resulting in internal oxidation occurring predominantly along the grain
      boundaries.

PMID- 16445011
TI  - Advantages of TOF-SIMS analysis of hydroxyapatite and fluorapatite in comparison
      with XRD, HR-TEM and FT-IR.
AB  - The chemical analysis of hydroxyapatite and fluorapatite was carried out using
      time-of-flight secondary ion mass spectrometry (TOF-SIMS). Hydroxyapatite and
      fluorapatite were synthesized at 80 +/- 1 degrees C and pH 7.4 +/- 0.2.
      Fluorapatite was better crystallized, with its (300) reflection shifted to a
      slightly higher angle. High-resolution transmission electron microscopy clearly
      revealed a typical, regular hexagonal cross section perpendicular to the c-axis
      for fluorapatite and a flattened hexagonal cross section for hydroxyapatite. FT
      IR spectra of fluorapatite confirmed the absence of OH absorption peak--which was
      seen in hydroxyapatite at about 3570 cm(-1). TOF-SIMS mass spectra showed a peak
      at 40 amu due to calcium. In addition, a peak at 19 amu due to fluorine could be
      clearly seen, although the intensities of PO, PO2, and PO3 were very low. It was
      confirmed that TOF-SIMS clearly showed the differences between positive and
      negative mass spectra of hydroxyapatite and fluorapatite, especially for F-. We
      concluded that TOF-SIMS exhibited distinct advantages compared with other methods
      of analysis.

PMID- 16445012
TI  - Fabrication of hydroxyapatite block from gypsum block based on (NH4)2HPO4
      treatment.
AB  - The aim of this study was to evaluate the feasibility of fabricating low
      crystalline, porous apatite block using set gypsum as a precursor based on the
      fact that apatite is thermodynamically more stable than gypsum. When the set
      gypsum was immersed in 1 mol/L diammonium hydrogen phosphate aqueous solution at
      100 degrees C, it transformed to low-crystalline porous apatite retaining its
      original shape. The transformation reaction caused a release of sulfate ions due
      to an ion exchange with phosphate ions, thus leading to a decrease in the pH of
      the solution. Then, due to decreased pH, dicalcium phosphate anhydrous--which has
      similar thermodynamic stability at lower pH--was also produced as a by-product.
      Apatite formed in the present method was low-crystalline, porous B-type carbonate
      apatite that contained approximately 0.5 wt% CO3, even though no carbonate
      sources--except carbon dioxide from air--were added to the reaction system. We
      concluded therefore that this is a useful bone filler fabrication method since B
      type carbonate apatite is the biological apatite contained in bone.

PMID- 16445013
TI  - Comparison of the occluding ability of dentinal tubules with different morphology
      between calcium phosphate precipitation method and potassium oxalate treatment.
AB  - The aim of this study was to evaluate the occluding ability of calcium phosphate
      precipitation (CPP) method and potassium oxalate treatment when each method was
      applied to dentin disks with different surface morphology. Occluding ability was
      observed by scanning electron microscopy. Irrespective of the diameter of the
      dentinal tubules, the CPP method showed a consistent occluding ability for
      dentinal tubules at the dentin surface, and that the depths of the precipitate
      formed in the dentinal tubules by CPP method were not significantly different. In
      contrast, the occluding ability of potassium oxalate treatment was reduced with
      increasing diameter of the dentinal tubules. However, the reduction of the
      occluding ability of potassium oxalate treatment was more markedly affected by
      the demineralization of dentin surface. Since the CPP method showed a consistent
      occluding ability irrespective of the diameter of the dentinal tubules, it is
      suggested that the CPP method would be a useful means for treating dentin
      hypersensitivity.

PMID- 16445014
TI  - Bonding properties of heat-polymerized denture base resin to Ti-6Al-7Nb alloy.
AB  - The purpose of this study was to evaluate the shear bonding strength and leakage
      of heat-polymerized denture base resin to titanium-aluminum-niobium (Ti-6Al-7Nb)
      and cobalt-chromium (Co-Cr) castings using four adhesive systems; three adhesive
      primers (Metal Primer II, Metal Link, MR. Bond) and one heat-polymerized adhesive
      resin containing 4-META (Metadent). The resin tab was heat-polymerized directly
      with or without the primer. Shear bonding strengths and dye penetration distances
      were determined before and after 10,000 times of thermocycling. The results were
      analyzed with three-way ANOVA and Tukey's comparison (p<0.05). Thermocycling
      significantly decreased bonding strength and promoted dye penetration. However,
      with the application of adhesive systems, post-thermocycling bond strength was
      significantly improved and dye penetration was inhibited. The bonding strength of
      Ti-6Al-7Nb was significantly smaller than that of Co-Cr, but the difference was
      marginal. These results suggested that the examined adhesive systems
      significantly improved the bonding efficiency of heat-polymerized resin to Ti-6Al
      7Nb and Co-Cr alloys.

PMID- 16445015
TI  - New surface modification of titanium implant with phospho-amino acid.
AB  - The purpose of this study was to investigate a new biochemical surface
      modification technique for titanium implants using phospho-amino acid. Pure
      titanium disks were pretreated with 10 N HCl and ultrapure water at room
      temperature for 30 minutes respectively. Then these disks were modified with
      either L-threonine (Thr) or O-phospho-L-threonine (P-Thr) at 37 degrees C for 12
      hours. X-ray photoelectron spectroscopy (XPS) chemically analyzed the modified
      surfaces. It was revealed that the N 1s peak which originated from Thr was not
      detected in the wide-scan spectrum of Thr-modified surface, whereas three peaks
      of N 1s, P 2s, and P 2p which originated from P-Thr were detected in the wide
      scan spectrum of P-Thr-modified surface. Moreover, the P 2p peak of P-Thr which
      reacted with the surface significantly shifted to a lower binding energy (p <
      0.05). Based on the results of this study, it was concluded that P-Thr chemically
      bonded to the titanium surface treated with HCl.

PMID- 16445016
TI  - Mechanical strength and microstructure of laser-welded Ti-6Al-7Nb alloy castings.
AB  - Mechanical properties of laser-welded castings of Ti-6Al-7Nb alloy, CP Ti, and Co
      Cr alloy were investigated and compared to the unwelded castings using a tensile
      test. Dumbbell-shaped specimens were cut at the center, and two halves of the
      specimens were welded with an Nd:YAG laser welding machine at 220 or 260 V of
      laser voltage. The mechanical strength of 260 V groups was higher than that of
      220 V groups for Ti-6Al-7Nb and Co-Cr alloys except for CP Ti. All 260 V laser
      welded castings of Ti-6Al-7Nb alloy and CP Ti, which fractured outside the welded
      joints, exhibited ductile characteristics, while all laser-welded Co-Cr alloy
      castings, which fractured within the welded joints, showed brittle
      characteristics. This study proved that the mechanical strength of laser-welded
      Ti-6Al-7Nb alloy and CP Ti castings was as high as that of unwelded castings,
      while the mechanical properties of laser-welded alloy joints were influenced by
      microstructural changes.

PMID- 16445017
TI  - Joint properties of cast Fe-Pt magnetic alloy laser-welded to Co-Cr alloy.
AB  - This study investigated the joint properties of Fe-Pt alloy laser-welded to Co-Cr
      alloy. Cast plates (0.5 x 3.0 x 10 mm) were prepared with Fe-Pt and Co-Cr alloys.
      Fe-Pt plates were butted against Co-Cr plates and laser-welded using Nd:YAG
      laser. Control and homogeneously welded specimens were also prepared. Laser
      welding was performed with and without argon shielding. Tensile testing was
      conducted, and both fracture force (Ff: N) and elongation (El: %) were recorded.
      There were no differences in the Ff value between the specimens with and without
      argon shielding for the welded Fe-Pt/Co-Cr. Lower Ff value of the welded specimen
      was obtained in the order of Fe-Pt alloy < Fe-Pt/Co-Cr < Co-Cr alloy. The results
      indicated that Fe-Pt welded to Co-Cr had Ff values between the values of
      homogeneously welded Fe-Pt and Co-Cr alloys. Argon shielding, on the other hand,
      had no effect on the weld strength between Fe-Pt and Co-Cr alloys.

PMID- 16445018
TI  - Development of self-setting Te-Cp/alpha-TCP cement for pulpotomy.
AB  - As an alternative to calcium hydroxide used as a direct capping agent, calcium
      phosphate cement that consisted of tetracalcium phosphate and alpha-tricalcium
      phosphate (Te-CP/alpha-TCP) at different molar ratios was developed with a one
      step method, in which heating was performed only one time. Alkalinity could be
      adjusted easily by changing the Te-CP/alpha-TCP ratio, whereby the mixing ratio
      of simple chemicals such as calcium carbonate and dicalcium phosphate dihydrate
      was changed. When mixed with a solution of 1 mol/L sodium dihydrogen phosphate,
      the cement set forming carbonate-containing apatite in revised, simulated body
      fluid (R-SBF)--which served to mimic the tissue fluid in dental pulp. The pH of
      the solution never exceeded 8.0 in the presence of the set cement even after
      about one month of storage. In contrast, with calcium hydroxide, the pH of R-SBF
      reached almost 12.0 on day 1 and remained at that value till the end of
      immersion. These findings clearly suggested that with Te-CP/alpha-TCP cement, its
      alkalinity would never exceed that of calcium hydroxide and that it would provide
      a mildly alkaline environment.

PMID- 16445019
TI  - In vitro study of DP-bioglass paste for treatment of dentin hypersensitivity.
AB  - Sealing of exposed dentinal tubules is generally considered the most effective
      strategy to treat dentin hypersensitivity. On this account, we fabricated a DP
      bioglass paste that created a homogeneous blockage on open dentinal tubules and
      formed a deep precipitate within dentinal tubules. DP-bioglass paste was prepared
      by mixing 20% to 60% phosphoric acid and DP-bioglass to treat dentin surfaces.
      CO2 laser irradiation was used to melt the DP-bioglass paste. The results
      demonstrated that 30% phosphoric acid was the optimum concentration to produce
      homogeneous occlusion on exposed dentinal tubules and 60 microm of sealing depth.
      CO2 laser irradiation could melt the DP-bioglass paste and create about 10 microm
      of sealing depth. Moreover, temperature rise during CO2 laser irradiation was
      only 4.86 +/- 0.47 degrees C. The results presented in this work suggested that
      DP-bioglass paste could produce considerable sealing depth in dentinal tubules
      with the potential of prolonging the therapeutic effect efficaciously.

PMID- 16445020
TI  - Immobilization of octadecyl ammonium chloride on the surface of titanium and its
      effect on microbial colonization in vitro.
AB  - The aim of our study was twofold: to immobilize an organosilicon quaternary
      ammonium salt (3-(trimethoxysilyl)-propyldimethyl-octadecyl ammonium chloride, Si
      QAC) on the surface of pure titanium and to investigate the antimicrobial
      activity of Si-QAC-immobilized titanium against microbial adherence and biofilm
      formation. The results of ToF-SIMS analysis of Si-QAC-titanium suggested the
      possibility of immobilizing Si-QAC on titanium surface through Ti-O-Si coupling,
      and that Si-QAC treatment significantly reduced both the adherence and
      colonization of Candida albicans and Streptococcus mutans isolates. The
      antimicrobial activity was achieved through at least two mechanisms: the first
      was attributed to the octadecyl alkyl chain which inhibited initial adherence,
      and the second was attributed to the quaternary ammonium salt which killed
      initial adherent cells as well as retarded or inhibited subsequent microbial
      growth. Further, thermocycling did not significantly reduce the antimicrobial
      activity of Si-QAC-titanium, and no significant cytotoxicity of Si-QAC-titanium
      was observed in either cell viability test or proinflammatory cytokine production
      test using human gingival fibroblasts. These results, taken together, favorably
      suggested that Si-QAC treatment would be a helpful means to inhibit dental plaque
      or denture plaque formation.

PMID- 16445021
TI  - Bond strength between four luting systems and enamel modified with phosphoric
      acid.
AB  - The purpose of this study was to investigate the effect of phosphoric acid
      etching on the bond strength between enamel and three luting materials employing
      self-etching primer (PanaviaF2.0, Linkmax, and Multibond). A luting material
      without self-etching primer (Super-Bond) was used as a control. Two etching
      agents (K-etchant and Red Activator) were prepared. The surfaces of bovine enamel
      were ground, etched with either K-etchant or Red Activator, and then bonded to a
      stainless steel rod. Tensile bond strengths were determined following 24-hour
      immersion in water. Without etching, all of the luting materials showed the same
      statistical bond strength. When K-etchant was applied, the bond strengths of
      PanaviaF2.0, Linkmax, Multibond, and Super-Bond were significantly greater than
      that of non-etched control. No significant differences were found between K
      etchant and Red Activator. Strongest bonds were obtained for Super-Bond in
      conjunction with K-etchant (23.6 +/- 6.3 MPa) or Red Activator (21.0 +/- 6.5
      MPa), whereby the values were statistically comparable.

PMID- 16445022
TI  - Biocompatibility of apatite-coated titanium mesh prepared by hydrothermal
      electrochemical method.
AB  - The hydrothermal-electrochemical method is best suited for producing homogeneous
      apatite coatings on electro-conductive materials with complicated shape, such as
      the mesh. This study was undertaken to examine the effect of the apatite coating
      prepared by this coating method on cell adhesion, proliferation, and
      differentiation of MC3T3-E1 cells in culture. The cells attached and spread well
      on the electrochemically deposited apatite on titanium mesh. The number of cells
      that adhered on the deposited apatite on titanium mesh was much greater than that
      on the surface without coating, and that it also depended on the morphology of
      apatites. When alkaline phosphatase activity as well as collagen and osteocalcin
      of the extracellular matrix were measured, the electrochemically apatite-coated
      titanium mesh showed higher measurement values than the titanium mesh without
      coating. These results suggested that the apatite-coated titanium mesh prepared
      by hydrothermal-electrochemical method has excellent biocompatibility.

PMID- 16445023
TI  - Effectiveness of an Er:YAG laser in etching the enamel surface for orthodontic
      bracket retention.
AB  - The purpose of this study was to test the effectiveness of an Er:YAG laser in
      etching the enamel surface for orthodontic treatment. Bovine incisors were either
      acid-etched or laser-treated. An orthodontic bracket was attached on each treated
      surface using one-step dentin adhesive and self-curing resin. Tensile bond
      strength was then evaluated. In addition, the surface morphology of specimens
      treated with phosphoric acid/laser and self-etching primer, as well as the cross
      section of enamel-primer-resin interfaces, were observed. One-Up Bond F-treated
      specimens after Er:YAG laser ablation showed statistically similar tensile bond
      strength (9.9 +/- 1.3 MPa) to that of phosphoric acid-etched specimens (11.8 +/-
      1.7 MPa). Surface roughness and thickness of the enamel-primer-resin interfaces
      did not much affect the tensile bond strength of the tested specimens. In
      conclusion, Er:YAG laser ablation achieved clinically acceptable level of tensile
      bond strength when used with One-Up Bond F.

PMID- 16445024
TI  - Application of direct laminate veneer for enamel protection during orthodontic
      treatment: an in vivo evaluation.
AB  - The aims of this study were to examine the enamel protective effect of a direct
      laminate veneer against acidic conditions, measure the amount of fluoride
      released from the veneer and which was taken up by the enamel, as well as
      evaluate the usefulness of the veneer for orthodontic treatment. First, a veneer
      was applied to rabbit incisors. Then, apart from using profile measurement
      microscope and electron probe microanalyzer to measure the roughness and fluoride
      concentration in the enamel of veneer-covered tooth surface, those of the
      uncovered adjacent tooth surface were measured too. It was found that the veneer
      protected the enamel surface from acidic conditions. Furthermore, fluoride ions
      were taken up by both the uncovered adjacent enamel area as well as by the
      covered area. These findings suggested that covering the enamel surface with a
      direct laminate veneer before bracket bonding might be a valuable means of tooth
      protection and caries prevention.

PMID- 16445025
TI  - Corrosion characteristics of alpha-Ti and Ti2Cu composing Ti-Cu alloys.
AB  - A series of binary Ti-Cu alloys containing 5-20 mass% Cu was prepared, and the
      corrosion behavior of alpha-Ti and Ti2Cu composing the Ti-Cu alloys were examined
      based on the anodic polarization curves and released ions in 0.9% NaCl and 1%
      lactic acid solutions. In both solutions, the Ti-Cu alloys showed the same anodic
      polarization curves as titanium in the condition below 1.4 V. However,
      precipitation of Ti2Cu contributed to a small increase in current densitiy in the
      transpassive region beyond 1.4 V. The amount of Cu ions released from Ti2Cu was
      0.260 and 1.003 (microg/cm2/7 days) in 0.9% NaCl and 1% lactic acid solutions
      respectively. Although these values were larger than those from alpha-Ti (0.0379
      +/- 0.0041 and 0.0962 +/- 0.0327 (microg/cm2/7days) in NaCl and lactic acid
      solutions respectively), they were not greater than those from type 4 gold alloy
      under the same conditions.

PMID- 16445026
TI  - Micro-shear bond strength of five single-step adhesives to dentin.
AB  - The micro-shear bond strengths (MSBSs) of five single-step self-etch adhesives
      (Adper Prompt L-Pop [APL], AQ Bond plus [AQP], OBF-2 [OB2], Reactmer Bond [RB],
      and Xeno III [XIII]) were compared with that of a two-step self-etch adhesive,
      Clearfil SE Bond [SE]. The adhesives were applied on dentin surfaces, according
      to manufacturers' instructions, for bonding of resin composite to dentin. After
      24 hours, a micro-shear bond test was carried out and the data were analyzed by
      one-way ANOVA and Bonferroni test (p<0.05). The mean MSBSs in MPa were APL: 22.8,
      AQP: 37.4, OB2: 34.7, RB: 28.3, XIII: 30.3, and SE: 47.2. Among the single-step
      adhesives, the MSBS of AQP and OB2 were significantly higher than APL (p<0.05).
      In conclusion, the single-step adhesives used in this study, apart from AQP,
      produced significantly lower MSBS than the two-step adhesive (p<0.05).

PMID- 16445027
TI  - The use of bioabsorbable implants as orthodontic anchorage in dogs.
AB  - The purpose of this study was to investigate the possibility of using a
      bioabsorbable implant as orthodontic anchorage. The implant under investigation
      in this study was a miniscrew, 2.0 mm x 8.0 mm, made from poly-L-lactic acid
      (PLLA; molecular weight: 200,000), a bioabsorbable bone-bonding material. The
      implants were placed in the mandibles of eight male beagle dogs. After
      implantation, traction was immediately applied to the third premolar (P3) using
      the implant as anchorage. After the completion of each study period (three and
      six months) following installation, tensile test, histological examination, and
      molecular weight measurement were performed. The results suggested that the
      bioabsorbable implant evaluated had favorable biocompatibility and strength, and
      that it showed promising potential for use in orthodontic treatment.

PMID- 16445028
TI  - Effect of radiation light characteristics on surface hardness of paint-on resin
      for shade modification.
AB  - The purpose of this study was to investigate the effect of radiation light
      characteristics--of different types of clinical light-curing unit--on
      polymerization efficiency, as determined by the surface hardness of light-cured
      paint-on resins. Four shades of paint-on resin for shade modification of
      restorative resins were used. Materials were cured using one laboratory and three
      clinical light-curing units with different light sources, namely tungsten
      halogen, LED, plasma arc, and xenon flash lamps. Knoop hardness measurements were
      taken at both the top and bottom surfaces of the specimens to assess the
      mechanical properties and degree of polymerization. Both LED and plasma arc light
      units caused significantly poorer surface hardness than the halogen and
      laboratory xenon lights. In addition, the transparent shade was more sensitive to
      surface hardness than other chromatic shades. Our results indicated that the
      polymerization efficiency of paint-on resin was significantly influenced by the
      radiation light characteristics of clinical light-curing units.

PMID- 16445029
TI  - Effect of acidic primers on bonding three magnetic steel alloys with tri-n
      butylborane initiated methacrylic resin.
AB  - The purpose of this study was to evaluate the effect of acidic primers on bonding
      magnetic steel alloys. Three alloys (XM27, 447J1, and AUM20) were primed with one
      of the following materials: Acryl Bond, Estenia Opaque Primer, Eye Sight Opaque
      Primer, M. L. Primer, or Super-Bond liquid. The specimens were bonded with a tri
      n-butylborane initiated resin, and bond strength was determined both before and
      after thermocycling in water. Unprimed specimen was considered as the control.
      Average bond strength varied from 0 to 45.3 MPa for the XM27 alloy, 0.3 to 43.6
      MPa for the 447J1 alloy, and 0.5 to 41.1 MPa for the AUM20 alloy. Of the five
      primers, Estenia Opaque Primer exhibited better adhesive performance than the
      other materials regardless of the type of steel alloy. It can be concluded that
      the use of the Estenia Opaque Primer, which contains an adhesive monomer (10
      methacryloyloxydecyl dihydrogen phosphate; MDP), is recommended for bonding the
      three magnetic steel alloys with TBB-initiated resin.

PMID- 16445030
TI  - Hardness and Young's modulus of transparent dentin associated with aging and
      carious disease.
AB  - This study investigated the changes in hardness and Young's modulus of the
      transparent layer of dentin associated with aging and the carious process.
      Eighteen extracted human molars with or without coronal caries were used in this
      study. The normal teeth were divided into two groups by age, and the carious
      teeth were divided into two groups of active or arrested caries. After polishing
      the specimens parallel to the long axis of the tooth, both hardness and Young's
      modulus were measured using a nanoindentation tester. The hardness and Young's
      modulus of the transparent layer in aged dentin were higher than the other
      portions of aged dentin. The transparent layer under carious lesions had a
      significantly lower hardness than the underlying normal dentin, whereas its
      Young's modulus was not significantly reduced. The hardness and Young's modulus
      of the transparent layer in active carious lesions were lower than those in
      arrested carious lesions.

PMID- 16445031
TI  - Effect of metal conditioner application on bond strength of luting cements to a
      noble metal.
AB  - The purpose of this study was to evaluate the adhesive performance of luting
      cements to a noble metal alloy treated with metal conditioners. Cast disk
      specimens made of a noble metal alloy were gritblasted with alumina followed by
      no treatment or priming with two different types of metal conditioner. A mold was
      placed on the metal surface and filled with luting cement. Ten samples per test
      group were stored in 37 degrees C distilled water for 24 hours, then shear tested
      at a cross-head speed of 1.0 mm/minute. ANOVA and Tukey's HSD tests (alpha=0.05)
      were done. The mean bond strength of resin-modified glass ionomer cement
      increased significantly with metal conditioner application compared to the
      controls, indicating the efficacy of the tested metal conditioners in improving
      bond strength. Based on the results of this study, it seemed to be a useful
      method to incorporate a functional monomer into resin cements so as to improve
      the bond strength to a noble metal alloy.

PMID- 16445032
TI  - Measurement of masticatory movement by a new jaw tracking system using a home
      digital camcorder.
AB  - The aim of this study was to confirm the precision of our simple and inexpensive
      jaw tracking system which combined the use of a digital camcorder and a motion
      capture software developed lately. A marker was attached to the mandibular
      incisors of the subject, and a mirror was assembled beside the subject's face to
      detect antero-posterior movement during chewing. Jaw movements, including the
      mirror images, were recorded by a digital camcorder. The movements were traced by
      a motion capture software and translated into 3D data using original handmade
      software. To confirm the beneficial performance of our system in measuring
      masticatory movement, the masticatory movements of five subjects were
      simultaneously recorded together with a conventional jaw tracking system.
      Trajectories obtained from both systems were similar, and the correlation
      coefficient values by simple regression analysis between both trajectories were
      0.9 or higher for all subjects. It was confirmed that our system could record
      masticatory movement with sufficient precision equivalent to that of a
      conventional jaw tracking system.

PMID- 16445033
TI  - Mechanical properties and bond strength of silicone-based resilient denture
      liners.
AB  - To evaluate the ease of manipulation and durability of 11 commercially available
      silicone-based resilient denture liners, extrusion force, hardness, weight
      change, and bond strength were determined. Extrusion force from the cartridge of
      each material ranged from 0.25 to 1.26 MPa at an extrusion rate of 1 cm/min.
      Durometer hardness, after set materials were stored in distilled water at 37
      degrees C for one day, ranged from A5.9 to A47.7, and after four weeks their
      values increased by 4.0 to 275%. Bond strength ranged from 1.01 to 2.88 MPa after
      set materials were stored in distilled water at 37 degrees C for one day, but
      decreased to 0.59 to 1.99 MPa after 10,000 thermal cycles. These results
      suggested that except for one material, the rest of the evaluated materials
      exhibited good handling properties--for example, mixing and spreading of material
      can be done easily. However, some materials exhibited inadequate durability for
      clinical service, because hardness increased during storage and/or bond strength
      decreased after thermal cycling.

PMID- 16445034
TI  - [Application of laparoscopic technologies in the treatment of peritonitis, caused
      by duodenal ulcer perforation].
AB  - Results of treatment of 105 patients suffering peritonitis, caused by duodenal
      ulcer perforation, using laparoscopic technologies were studied up. In terms up
      to 6 hours from the perforation occurrence 68 (64.8%) patients were admitted to
      the hospital, from 6 to 12 hours--23 (21.9%), from 12 to 24 hours--14 (13.3%).
      Local peritonitis was diagnosed in 12 (11.4%) patients, extended one--in 71
      (67.6%), general--in 22 (21%). Serous peritoneal exudate was revealed in 65
      (61.9%) observations, serofibrinous one--in 27 (25.7%), fibrinopurulent--in 13
      (12.4%). The peritoneal cavity sanation, depending on the inflammation character
      and extension, was performed using from 1 to 91 of antiseptic solution and
      assistance of irrigation-aspiration system. Necessity to perform conversion have
      occurred in 3 (2.8%) patients in presence of intestinal paresis, necessitating
      the intestinal intubation performance. In 7 (6.7%) patients, admitted to hospital
      in terms later than 12 hours from the ulcer perforation moment, in 12-24 hours
      after laparoscopic operation performance the elective videolaparoscopic sanation
      of peritoneal cavity was done.

PMID- 16445035
TI  - [The choice of tactics in the treatment of nonspecific ulcerative colitis].
AB  - Taking into account high probability of occurrence of the colonic mucosa
      morphological atypia in nonspecific ulcerative colitis, the methods of
      trustworthy diagnosis of dysplasia determine the choice of the treatment tactics
      as well as the operative intervention volume. The methods of chromocolonoscopy
      and photodynamical diagnosis of nonspecific ulcerative colitis are presented,
      their role in the treatment of patients tactic and considering the operative
      intervention volume was determined.

PMID- 16445036
TI  - [Assessment of nutritional status in patients, operated on the colon].
AB  - In 54 patients, operated on the colon, the indexes of nutritive status - body
      mass index, the shoulder circumference, the circulating albumin level and the
      leukocytes count - were estimated on the third and the tenth postoperative day.
      On the third day after the operation the lowering of these indexes was noted in
      the patients. Postoperative disorders of nutrition after colonic interventions
      have multifactorial mechanism of pathogenesis and need complex approach for their
      correction.

PMID- 16445037
TI  - [Application of octrestatin in the treatment of patients with acute
      pancreatitis].
AB  - The influence of preparation Octrestatin, manufactured by Russian company "Pharm
      Synthesis", on activity of amylase in the blood and urine in dynamic among 38
      operated persons and 79 patients with an acute pancreatitis, who were not
      operated, was analyzed. There was established high efficacy of Octrestatin
      application as an inhibitor of pancreatic secretion, possible faster
      normalization of the amylase activity in the blood and urine, and prophylaxis of
      the wave-like course of the disease also.

PMID- 16445038
TI  - [Aortopexy in the surgical treatment of tracheomalacia in children].
AB  - Aortopexy was performed in 55 patients for respiratory ways obstruction of
      various origin. There were estimated immediate and late follow-up results of
      aortopexy application, solely or in conjunction with tracheoplasty in 11
      patients, ageing from 1 mo to 5 years, performed for tracheomalacia, which
      included idiopathic, associated with esophageal atresia and tracheoesophageal
      fistula forms. Local tracheomalacia was revealed in 8 patients, diffuse--in 3. In
      6 observations aortopexy was conducted only, in 5 - aortopexy in conjunction with
      tracheoplasty using pericardial or fasciopleural flaps. In presence of esophageal
      disease concominantly its segmental resection of cicatricially changed portion
      was performed, as well as the recurrent tracheoesophageal fistula division and
      suturing. Generally, positive result in immediate and late follow-up period was
      noted in all the patients. In 3 patients there was revealed incomplete
      stabilization of trachea with the membranous portion of the wall expulsion up to
      1/2 of lumen and persistence of nonsignificant respiratory symptoms, caused by
      presence of gastro-esophageal reflux. The results obtained witness, that
      aortopexy constitutes an effective method of surgical treatment of respiratory
      ways obstruction, caused by tracheomalacia. The presence of diffuse
      tracheomalacia needs additional tracheoplasty to the aortopexy performance.

PMID- 16445039
TI  - [Method of suturing of the soft tissues wound].
AB  - Method of the wound suturing, guaranteeing the plain distribution of pressure
      toward the soft tissues displaced and maximal usage of their elastic properties,
      was proposed. II-figure sutures were placed on the both edges of the wound, from
      the beginning--on the flaps base, then--on the middle and at last--on the edges.
      On the wound there were placed interrupted, continuous and other cosmetic kinds
      of sutures, permitting to distribute the load while approximating the wound edges
      along all the flaps surface, to eliminate the tension from the proper cutaneous
      suture for creating favorable conditions for the cosmetic cicatrix formation. The
      method was applied in 15 patients with vast defect of soft tissues in
      maxillofacial region. There were closed the irregular form defects owing from 10
      to 50 cm2.

PMID- 16445040
TI  - [The prolonged intraarterial medicinal therapy of the destructive forms of
      diabetic foot syndrome].
AB  - The results of surgical treatment of 76 patients. suffering diabetes mellitus
      with purulent--necrotic affection of the foot. were analyzed. In 48 of them the
      selective prolonged intraarterial medicinal therapy was conducted. The efficacy
      of durable application of intraarterial desaggregant and antibacterial therapy
      was substantiated, permitting to perform predominantly "small" operation on the
      foot and to save its supportive function in 96% of observations.

PMID- 16445041
TI  - [The place and the meaning of cerebrospinal anaesthesia in modern surgical
      practice].
AB  - The modern views concerning application of cerebrospinal anaesthesia in surgical
      practice were presented. Although last 15 years many new preparations for general
      anaesthesia have appeared on the pharmaceutical market of Ukraine, but the
      cerebrospinal anaesthesia did not lose its actuality. While performing
      cerebrospinal anaesthesia the one-use instruments are applied. It constitute
      significant factor of the hepatitis and AIDS prophylaxis. Surgeons have had
      acknowledged in the cerebrospinal anaesthesia security and safety. There were
      analyzed the results of the cerebrospinal anaesthesia application in more than
      6200 patients for the 7-year period of work of the clinical hospital surgical
      departments. It was proved, that cerebrospinal anaesthesia constitutes secure,
      safe, simple and not expensive method of anaesthesia.

PMID- 16445042
TI  - [The reasons of the recurrence of polynodous euthyroid goiter].
AB  - The results of surgical treatment of 150 patients with polynodous euthyroid
      goiter were studied. There was shown the influence of various factors on the
      disease recurrence frequency.

PMID- 16445043
TI  - [Possibilities of investigation of the tissues extracts using method of the laser
      correlative spectroscopy in differential diagnosis of the thyroid gland cancer
      and chronic autoimmune thyroiditis].
AB  - The results of investigation of the intraoperatively excised tissues extracts
      using method of the laser correlative spectroscopy were analyzed. Application of
      laser correlative spectroscopy permit to differentiate the thyroid gland cancer
      and chronic autoimmune thyroiditis in 82% of observations.

PMID- 16445044
TI  - [The choice of operative intervention in combined treatment of malignant tumors
      of the adrenal glands].
AB  - Comparative efficacy of various kinds of surgical treatment for malignant tumors
      of adrenal glands (MTAG) was studied. Traumaticity of various kinds of operations
      was estimated. There were operated on 318 patients, suffering MTAG: in 280-
      primary interventions were performed and in 38--reoperations. An optimal surgical
      intervention constitutes the adrenal gland excision en bloc with the tumor and
      performance of systemic lymph nodes dissection (LND) of paranephral, paraaortal
      (left--sided) and paracaval (right-sided) collectors. Adrenalectomy (AE) with LND
      of retroperitoneal space is the operation of choice in the MTAG treatment.
      Performance of AE with the tumor excision en bloc with LND, foreseeing high
      efficacy of the treatment, is possible in I-II stages of tumor only, when its
      malignant character could not be confirmed pre- or intraoperatively.

PMID- 16445045
TI  - [The brain dislocation and its significance in surgical treatment of patients
      with glioma of supratentorial localization].
AB  - Results of surgical treatment of patients with glioma of supratentorial
      localization were analyzed. The diagnosis, prophylaxis and treatment methods
      optimization was done, basing on prognostication of postoperative dislocation
      complications (DC). The DC frequency in surgical treatment of patients, suffering
      glioma of a big brain hemispheres, their role in the postoperative mortality
      structure were determined. Prognostic power of several factors, influencing the
      risk of the postoperative DC occurrence, was established. Basing on clinico
      statistical prognostication, the clinico-diagnostic standards and algorrhythms of
      prophylactic and curative measures were elaborated and introduced into
      neurooncological practice for patients, suffering glioma of supratentorial
      localization, and directed on minimization of risk of the DC occurrence, caused
      by oedema of brain, hematological and liquorocirculation disorders. Introduction
      of diagnostic and prophylactic algorrhythms, standards of treatment have promoted
      improvement of the patients treatment results, postoperative mortality lowering
      in 2,17 times.

PMID- 16445046
TI  - [Transplantation of the muscular perforant flaps for restoration of tissues
      defects in the extremities].
AB  - There was summarized the experience of surgical treatment of 9 patients with the
      soft tissues defects of various etiology, localization and size, in whom
      microsurgical autotransplantation of the perforant flaps was performed on
      thoracospinal and medial gastrocnemial arteries. Peculiarities of preparation and
      mobilization of perforating vessels, securing the motor nerves branches, were
      presented. The perforant flaps advantages are: their small thickness, plasticity,
      mobility and minimal complications in the donor's zone. The perforant flaps
      advantages secure the wider diapason of their usage comparing with conventional
      composed complexes of tissues.

PMID- 16445047
TI  - [Peculiarities of the microsurgical discectomy for hernia of the low-lumbar
      vertebral column].
AB  - There were analyzed the results of observation in 642 patients with hernia of low
      lumbar vertebral column, who were examined and operated on using microdiscectomy
      in the Department of endoscopic and laser spinal neurosurgery of Institute of
      Neurosurgery of Academy of Medical Sciences of Ukraine. There were delineated the
      indications for the methods of treatment, their efficacy was estimated, the
      immediate and late follow-up results of treatment were studied up. In one year
      after the medial hernia correction the persistent elimination of radicular
      compression syndrome was achieved in 86.5% of observations, after paramedian one-
      in 88.7% and postero-lateral--in 95.7%.

PMID- 16445048
TI  - [The models of hepatic insufficiency and encephalopathy in animals].
AB  - The majority of the investigation methods of biochemical, morphological and
      metabolic disorders in hepatic insufficiency and encephalopathy occurrence are
      inadequate in use in clinical conditions because their invasiveness frequently
      creates dangerous situations to the patient life and health. That's why, to
      characterize the mechanisms, constituting the hepatic and cerebral damages base,
      for testing of a new medicinal preparations, aprobation of a new theoretical and
      clinical hypotheses, the models of an acute and chronic hepatic insufficiency are
      applied on the animals, permitting to unify the age, genetic peculiarities and
      physiological parameters of the individuals involved in experiments, the
      pathology character, its severity and longevity. Homogeneity of these indexes
      permits to estimate molecular, structural and functional disorders, laying in the
      base of pathological process. We have analyzed the experimental models of hepatic
      insufficiency, basing on the hepatotoxins usage--acetaminophen (paracetamol),
      carbon tetrachloride, thioacetamide, D-galactosamine, concanavalin A,
      lipopolysaccharides. Every existing pharmacological model of hepatic
      insufficiency and encephalopathy for animals owes its own advantages and faults.
      The choice of a model depends on tasks of the investigation and of the animal
      species, involved in the procedures.

PMID- 16445049
TI  - [Intraperitoneal rupture of the bladder, simulating the perforative
      gastroduodenal ulcer symptoms].

PMID- 16445050
TI  - [Tuberculous lesion of the spleen].

PMID- 16445051
TI  - [Main principles of antibiotic prophylaxis and antibacterial therapy in abdominal
      surgery].
AB  - The principles of antibioticoprophylaxis and antibacterial therapy in abdominal
      surgery were expounded. There are adduced the most frequently revealed pathogenic
      microorganisms, inducing intraabdominal infection, the ways of lowering of the
      antibacterial therapy expenses, new approaches to application of immunocorrection
      and directed transport of antibiotics in surgery as well as empirical and
      etiotropic treatment, basing on the taking account of the spread and
      antibioticosensitivity of pathogenic microorganisms of nosocomial infections.
      There was shown, that concentration of interleucin-1beta and tumor necrosis
      factor-alpha in the blood serum is connected with the severity of patient state.
      Significant rising of this cytokines concentration constitutes the trustworthy
      criterion of the ineffective therapy and mortality risk. The influence of
      microorganisms and some antibiotics on induction of interferons was studied.
      Amoxicyllin, polymixin, vancomycin, cephalosporins and fluconazol are the most
      active inductors of gamma-interferon. Maximal efficacy of antibacterial therapy
      is possible only if an adequate surgical intervention was performed.

PMID- 16445052
TI  - [Possibilities of application of palliative cryodestruction for the treatment of
      patients with nonresectable local recurrence of rectal cancer].
AB  - The cancer recti local recurrence is nonresectable in 50-70% of observations, it
      is treated using irradiation or chemo-irradiation therapy, which improve the
      patients quality of life and guarantee the 12-13 mo survival mediana. In
      subsequent progressing disease cryosurgical method of treatment is applied. The
      results of it application in 22 patients are presented. The survival mediana had
      constituted 12 mo, the period of time before subsequent progression of the
      disease--6 mo. The patients quality of life improvement due to the bleeding
      stoppage, the tumor destruction, the pain elimination achievement was proved by
      the ECOG scale changes.

PMID- 16445053
TI  - [The prognostic factors of the colonic cancer occurrence in nonspecific
      ulcerative colitis].
AB  - The prognostic factors of the colonic cancer occurrence in nonspecific ulcerative
      colitis were determined. Photodynamical diagnosis of the colonic mucosa
      affection, immunohistochemical determination of proliferation and apoptosis
      markers were applied in the investigation. The statistic-probability pattern of
      the malignization processes dynamics was elaborated. Algorhythm of the colonic
      cancer and nonspecific ulcerative colitis prognostication and diagnosis was
      proposed.

PMID- 16445054
TI  - [Peculiarities of course of postoperative peritonitis].
AB  - Retrospective analysis of severity of the postoperative peritonitis clinical
      course was conducted in 69 patients. There were identified two forms: classical
      and atypic. There was established, that for classical clinical form the presence
      of the pain syndromes characteristic as well as of the peritoneal irritation
      symptoms, and for the atypic one--the sepsis occurrence.

PMID- 16445055
TI  - [An acute necrotic pancreatitis as a complication of cystic pancreatic tumor].
AB  - The peculiarities of the cystic pancreatic tumor morphogenesis were studied up.
      Possibility and probability of the anastomosis existence between mucinous cystic
      tumor and pancreatic duct with its secondary mucinous dilatation were confirmed,
      causing the complications occurrence, an acute pancreatitis in particular.
      Selecting the surgical tactic in mucinous cystic tumor it is necessary to take
      into account the probability of the intraductal malignization foci formation,
      what precludes application of extended pancreatic resection using adjuvant
      chemotherapy and the postoperative serological control conduction.

PMID- 16445056
TI  - [Metabolic disorders after performance of total pancreatectomy].
AB  - The literature data concerning metabolic disorders after performance of total
      pancreatectomy and the results of analysis of this intervention, done in 2003
      2004 yrs in 4 patients are presented.

PMID- 16445057
TI  - [Clinical significance of K-RAS and cytokeratine 20 markers in diagnosis of
      lymphogenic metastasis of pancreatic cancer].
AB  - Aim of the work is to estimate the role of the metastases molecular signs (MMS)
      in paraaortal lymphatic nodes, revealed using combined molecular-biological
      method with application of K-RAS markers and cytokeratine 20 (CK20) for the
      survival prognostication in the pancreatic head cancer patients after performing
      pancreatoduodenal resection. Actuarial index of general survival of the patients
      with MMS in paraaortal lymphatic nodes was trustworthy lower than in patients
      without such a signs. The two-year survival index in patients without MMS was
      60%, the survival mediana--32 mo. Any of the patients with MMS did not survive
      two years, the survival mediana was 13 mo.

PMID- 16445058
TI  - [Experience of utilization of laparoscopic stand in central district hospital].
AB  - The experience of application of laparoscopic operations in conditions of central
      hospital of district in 2003-2004 yrs was summarized. There were analyzed the
      results of application of laparoscopic technologies in 116 patients. In 90 of
      them the intervention was performed for various clinical forms of cholelithiasis,
      in 26--for other surgical diseases of abdominal cavity organs. The performance of
      laparoscopic operations have promoted the reduction of the treatment duration in
      surgical stationary and shortage of the temporary disablement period.

PMID- 16445059
TI  - [Clinical and ultrasonographic diagnosis of angiodysplasia].
AB  - Diagnosis and treatment of the inborn angiodysplasia constitutes the complex
      problem of vascular surgery. Of the multiple causes, conditioned by such the
      state of the issue, it is necessary to stress such as unsatisfactory knowledge of
      physician, the absence of strict diagnostic criterions, the attempts of the
      pathology elimination by specialists of various disciplines. The aim of the
      investigation was to determine the principal clinical and ultrasonographic
      criterions, permitting to reveal vascular malformation rapidly and objectively,
      to differentiate its type, the spreading, to characterize hemodynamical
      disorders.

PMID- 16445060
TI  - [The severity of varicose vein disease of the lower extremities in various degree
      of the connective tissue dysplasia syndrome].
AB  - There were examined 80 patients with varicose disease of the lower extremities
      veins (VDLEV) using elaborated phenotypic cart, the Bayton scale, ECG,
      echocardiography and ultrasonic triplex phleboscanning. There were defined 24
      markers of the connective tissue dysplasia, mostly characteristic for VDLEV.
      Correlation was established between the phenotypic signs number, the severity of
      clinical course and the rate of occurrence of the venous diseases complications.
      Moderate and severe clinical course of VDLEV is associated with various
      phenotypic markers of the connective tissue dysplasia.

PMID- 16445061
TI  - [Endoscopic recanalization of the respiratory ways as the stage of radical
      surgical treatment of tracheal and bronchial stenosis of tumoral origin].
AB  - The experience of the laser and electrocoagulational recanalization conduction of
      the respiratory ways stenosis portions in 118 patients with respiratory organs
      tumors was summarized. There was established the probability of the
      recanalization application for tumoral and cicatricial tracheobronchial stenosis.
      The advantages of various bronchoplastic operations application after performance
      of endoscopic recanalization of tracheobronchial tree were noted. After
      performance of endoscopic recanalization of respiratory ways all the patients are
      alive.

PMID- 16445062
TI  - [Using ultrasound investigation in differential diagnosis of adrenal malignant
      tumors].
AB  - Possibilities of ultrasound investigation (USI) application for differential
      diagnosis of the suprarenal glands tumors (SGT) were studied. USI was conducted
      in 169 patients with SGT, including 95 with malignant tumors of suprarenal glands
      (MTSG) and 64--with benign SGT. USI constitutes the main method of screening,
      permitting to reveal SGT in 90.5% of patients. Diagnostic criterions of MTSG
      were: diameter of tumor exceeding 10.1 cm, incorrect form, irregular edges,
      presence of invasion, lymphadenopathy, regional and remote metastases. In 45.3%
      of observations it was possible to establish the MTSG diagnosis, using USI.

PMID- 16445063
TI  - [Correction of the glicemia level in elderly and senile patients with diabetes
      mellitus, operated for purulent-necrotic foot lesion].
AB  - Basing on the analysis of surgical treatment experience of 685 elderly and senile
      patients with diabetes mellitus, suffering purulent-necrotic affection of foot,
      the authors admit possibility of the insulinotherapy abolition before the
      operation in patients with for the first time diagnosed diabetes type II or in
      those, who before hospitalization received preparations in tablets, while the
      signs of intoxication are absent (extended purulent process, humid gangrene) and
      initial level of glycemia no more than 10 mmol/l.

PMID- 16445065
TI  - [Surgical treatment of the abdominal aorta atherosclerotic aneurysm after
      performance of gastric subtotal resection for cancer].

PMID- 16445064
TI  - [Actinomycosis of the peritoneal and retroperitoneal space].

PMID- 16445066
TI  - [The treatment of isolated esophageal wound].

PMID- 16445067
TI  - [The rare purulent-septic complication of the bladder foreign body].

PMID- 16445068
TI  - [Penetrating wound of the small pelvis in a child].

PMID- 16445069
TI  - [Expediency of combined gastrectomy for gastric cancer].

PMID- 16445070
TI  - Asthma in adolescence.

PMID- 16445071
TI  - Young people, social support and help-seeking.
AB  - This paper contributes to understanding of young people's help-seeking behaviour.
      A conceptual framework is proposed that seeks to integrate differing sources of
      influence and their implications for policy and programme development. Data was
      collected by means of an international literature review followed by a purposive
      international survey of expert informants. Findings suggest that it is important
      to distinguish between individual and structural determinants of young people's
      help-seeking behaviour. Policy and programme influences also impact upon the
      demand for help and the supply of social support that is available. It is
      important to focus on the normative needs of young people as well as specific
      health needs and problems. Creating trust, rethinking adult attitudes toward
      young people, and reducing the stigma associated with seeking help are key to
      promoting help-seeking behaviour. Many young people are hindered from seeking
      help, or are not offered help because of social exclusion, violence, poverty,
      prejudice (including homophobia) and gender inequalities. Future actions to
      promote help-seeking and enhance social support must consider these structural
      barriers, making special efforts to reach and work with excluded populations.

PMID- 16445072
TI  - Measles seroprevalence of an adolescent population vaccinated with a single dose
      of measles vaccine before their first birthday.
AB  - This study determined the age-specific measles seroprevalence of an adolescent
      population in Ankara vaccinated with a single dose of measles vaccine before
      their first birthday. The study sample included 440 adolescents (227 female, 213
      male) aged 9-16 years admitted to the Adolescent Outpatient Clinic of Hacettepe
      University Faculty of Medicine. For each participant, a questionnaire was
      completed and measles specific IgG antibodies screened quantitatively by the
      enzyme linked immunosorbent assay. Of the 440 subjects screened for measles
      antibodies, 114 (25.9 %) were seronegative. Measles seronegativity according to
      sex and age groups were, 32.6, 24.7, 13.3% in females and 29.5, 30.1, 6.3% in
      males in the age groups of 9-11, 12-14, 15-16 years, respectively. In countries
      where the two dose vaccination schedule against measles has not been incorporated
      to the national immunization program, the adolescent health maintenance visit at
      age 11-12 years should serve as an opportunity to evaluate vaccination status and
      administer MMR vaccine to all adolescents who have not received two doses at the
      recommended ages.

PMID- 16445073
TI  - An innovation in drug prevention programs for adolescents: the Hong Kong Astro
      project.
AB  - Recent approaches to drug prevention have turned to focus on comprehensive
      strategies that target early risk factors and that strengthen protective factors
      in adolescence. OBJECTIVE: To develop a drug prevention program that is evidence
      based and conceptually sound for the Chinese community. STUDY GROUP: The "Astro"
      project was designed for high-risk youths in Hong Kong and consisted of three
      psychosocial primary prevention programs conducted in structured group sessions.
      METHODS: A three-year longitudinal study and control group comparisons are
      integrated in this project for the program evaluation. RESULTS AND CONCLUSIONS:
      The findings showed that the experimental group, after participating in the
      programs, was generally better than the control group in terms of social skills,
      knowledge of drugs, refusal skills, attitudes towards drugs, and the behavioral
      intention to avoid drug abuse. It suggests that this program could function well
      as a drug prevention program.

PMID- 16445074
TI  - Effects of the holding technique for restraint of aggression in children in
      residential care.
AB  - The purpose of the present study was to further understanding of the therapeutic
      value of the holding technique for children who exhibit extreme uncontrolled
      behavior. The data collection in this study was from reports on the use of the
      holding technique and a questionnaire based on the RAF (regulation, assessment,
      follow-up) Method, which includes three subscales of a Teacher's Report Form
      questionnaire (TRF): Social Problems, Aggressive Behavior and Anxious/Depression.
      The RAF questionnaires were administered to 91 children in a residential care
      facility of which 51 underwent holding. The questionnaires were administered
      twice with an intervening period of one year indicating no improvement in the
      indices examined, including aggressive behavior, but suicide attempts in children
      who were held declined.

PMID- 16445075
TI  - Verbal abuse, gender and well-being at school.
AB  - The purpose was to assess the prevalence of students' experience of verbal abuse
      and its effects on school satisfaction and well-being from a gender perspective.
      Attention was paid to age differences. METHODS: The study population consisted of
      all students in grades 6 and 8 in a Swedish city. A total of 1,006 students, ages
      12-15, completed a self-administered questionnaire (response rate 84 percent).
      RESULTS: Boys reported experiencing insults and threats to a greater extent,
      whereas girls more frequently experienced sexualized name-calling, specifically
      "whore". Both genders reported boys as perpetrators of verbal abuse most often.
      Further, girls generally reported lower levels of school satisfaction and well
      being, while verbal abuse had a negative effect on the well-being of both
      genders. CONCLUSIONS: Verbal abuse between students is a predominantly masculine
      practice, more pronounced among older students. It impacts negatively on the
      school satisfaction and well-being of both girls and boys and does not have to be
      frequent, repeated, or combined with other kinds of harassment to have this
      effect.

PMID- 16445076
TI  - Gender differed factors affecting male condom use. A population-based study of 18
      year-old Swedish adolescents.
AB  - Despite preventive measures promoting the condom as a good barrier method and a
      good preventive measure for STIs, teenage abortions and STIs are increasing in
      our society. OBJECTIVE: The aim of this study was to explore which male factors
      are associated with non-condom use and also which female factors are associated
      with non-condom use among their sexual partners. STUDY GROUP: A population-based
      study, among all 18-year old girls and boys in four cities in northern Sweden.
      METHOD: The participants answered a questionnaire regarding their social
      lifestyle, psychological-, and sexual health. The associations between the
      independent variables and the dependent variable (non-condom use) were
      investigated by multivariate logistic regression analysis. RESULTS: Four
      significant (p<0.05) male variables associated with non-condom use were
      identified: living with partner during the weekends, feeling depressed, being a
      party smoker, and girl partner taking oral contraceptives. Two significant
      (p<0.05) female variables were associated with non-condom: using oral
      contraceptives and feeling forced into sex. Having TV and movie watching as
      favourite free time activity was identified as a significant protective female
      variable associated with condom use. CONCLUSION: The study found several male and
      female factors associated with non-condom use, where the usage of oral
      contraception was the strongest indicator for non-condom use. The study showed a
      gender difference in the variables associated with condom use and the results
      have been suggested as useful in future preventive measures promoting condom
      usage.

PMID- 16445077
TI  - Have you been sexually harassed in school? What female high school students
      regard as harassment.
AB  - The aim of the study was to explore what behaviors experienced from peers and
      school staff at school are acknowledged as sexual harassment, and perceived as
      problematic, by female high school students, and what other factors may be
      relevant. Analyses were performed of responses (to 540 questionnaires) in an
      anonymous self-report mail survey from a random sample of female Swedish high
      school students (59% response rate). Exposure to relevant behaviors, of varying
      levels of severity, alone, does not explain the acknowledgment of harassment.
      Many students were subjected to many of the potentially offensive behaviors
      without labeling them as sexual harassment, despite the fact that they saw many
      of them as problematic. Further, viewing the relevant behaviors as problems in
      one's school did not necessarily lead to acknowledging that sexual harassment in
      general was a problem. However, the behaviors seen as problems were less likely
      to be dismissed as sexual harassment than personal experiences. This was
      especially true of the most common behaviors, namely verbal ones. The results
      demonstrate female students' reluctance to label incidents as sexual harassment,
      despite the fact that actual behaviors are perceived as environmental problems.
      Potentially offensive sex-related behaviors become normalized in the school
      environment and are difficult to address, when little support is provided by
      schools.

PMID- 16445078
TI  - Environmental fate of the antifouling compound zinc pyrithione in seawater.
AB  - To perform a thorough risk assessment of the new antifouling compound zinc
      pyrithione (ZnPT2), additional information regarding the fate of the compound is
      needed. The present study examined the recovery and transchelation of ZnPT2 in
      controlled laboratory experiments, photodegradation experiments, and a fate study
      in a large-scale field experiment. Chemical analyses were performed using a newly
      developed method for simultaneous analyses of ZnPT2 and copper pyrithione
      (CuPT2). Furthermore, two antifouling paints containing ZnPT2 were examined for
      the fate of leaching biocide. Naturally occurring ligands and metals in seawater
      influence the stability of ZnPT2. The presence of free Cu2+, which is present
      naturally in the seawater or is released from copper-containing paints, results
      in a partial transchelation of ZnPT2 into CuPT2. A complete transchelation of
      ZnPT2 into CuPT2 was observed when Cu2+ was present at an equimolar concentration
      in the absence of interfering ligands. When ZnPT2 was leached from antifouling
      paints containing both ZnPT2 and Cu2O, CuPT2 was found, with no trace of ZnPT2.
      Photodegradation was low in natural waters and absent from 1 m or more below the
      surface. The results show that ZnPT2 has a low persistence in seawater when
      leached from antifouling paints. However, the more stable and toxic
      transchelation product CuPT2 is formed, which has the potential to accumulate in
      the sediments and, therefore, should be included in both chemical analysis and
      risk assessment of ZPT2.

PMID- 16445079
TI  - Experimental and modeling investigation of metal release from metal-spiked
      sediments.
AB  - In sediments that contain iron monosulfide, cadmium, nickel, lead, zinc, and
      silver(I) form insoluble metal sulfides that lower the metal ion activity in the
      sediment-pore water system, thereby reducing toxicity. However, metal sulfides
      are susceptible to oxidation by molecular oxygen resulting in metal
      solubilization. To better understand the sources and sinks of metal sulfides in
      sediments, iron monsulfide-rich freshwater sediments were spiked with cadmium,
      nickel, lead, zinc, or silver(I) and placed into cylindrical cores with an
      overlying layer of oxygen-saturated water. Measurements of the dissolved metal
      concentration in the overlying water were made as a function of time and the
      vertical profiles of acid-volatile sulfide (AVS) and simultaneously extracted
      metal (SEM) were measured after 150 d. A one-dimensional reactive and transport
      model has been employed to help elucidate processes controlling the fate of
      metals in sediments. The model incorporates metal-sulfide formation, metal
      sulfide oxidation, and metal partitioning onto sediment organic carbon and iron
      oxyhydroxide to simulate the vertical transport of metals throughout the sediment
      core.

PMID- 16445080
TI  - Slow desorption behavior of one highly resistant aromatic amine in Lake Macatawa,
      Michigan, USA, sediment.
AB  - The desorption behavior of benzidine from Lake Macatawa (Holland, MI, USA)
      sediment was investigated in this study using batch solvent extraction method.
      Seven solvents were tested as the extracting reagents: Deionized water (DI),
      calcium chloride in DI (CaCl2), sodium hydroxide in DI (NaOH), acetonitrile
      (ACN), a mixture of acetonitrile and ammonium acetate in DI (ACN-NH4OAc),
      methanol (MeOH), and hydrochloric acid in DI (HCl). These solvents are proposed
      to react with sediment-associated benzidine by different mechanisms (e.g., cation
      exchange, hydrophobic partitioning, and covalent binding). Three sets of sorption
      isotherm experiments were conducted separately in these seven solvents with a 7
      d, three-week, and two-month contact time. The results demonstrated nonlinear
      isotherms with Freundlich 1/n values varying from 0.25 to 0.52. The desorption
      behavior of benzidine in the solvents was evaluated after the sorption of
      benzidine onto the sediment with same contact times of 7 d, three weeks, and two
      months. A two-stage model subsequently was applied to simulate the experimental
      data. The rapidly desorbing rate constants were on the order of one to two per
      day for ACN, ACN-NH4OAc, and NaOH solvents, and the slowly desorbing rate
      constants were on the order of 10(-5) to 10(-4)/d. Sequential desorption
      experiment demonstrated low total extraction efficiency of less than 40%. Both
      the observed sorption and desorption phenomena suggested that hysteresis and/or
      mass-transfer limited diffusion may result in the slow desorption behavior
      observed in this study.

PMID- 16445081
TI  - Biochemical responses of the aquatic higher plant Lemna gibba to a mixture of
      copper and 1,2-dihydroxyanthraquinone: synergistic toxicity via reactive oxygen
      species.
AB  - Metals and polycyclic aromatic hydrocarbons (PAHs) are known to be toxic to
      plants. Because metals and PAHs often are cocontaminants in the environment,
      plants can be subjected to damage caused by their combined effects. We recently
      found that copper and an oxygenated PAH (1,2-dihydroxyanthraquinone [1,2-dhATQ])
      synergistically are toxic to plants. This synergistic toxicity was linked
      indirectly to production of reactive oxygen species (ROS). In this study, plant
      growth, chlorophyll pigments, protein accumulation, and ROS production were
      chosen as endpoints to assess the mechanism of toxicity of copper and 1,2-dhATQ
      to Lemna gibba in more detail. Because copper and PAHs can generate ROS, we
      assayed for specific antioxidant enzymes: Superoxide dismutase (SOD), glutathione
      reductase (GR), and ascorbate peroxidase (APX). Copper treatment at a
      concentration that did not cause growth inhibition resulted in upregulation of Mn
      SOD, Cu-Zn SOD, and APX. At a level that moderately was toxic to plants, 1,2
      dhATQ did not alter significantly the levels of these antioxidant enzymes.
      However, a synergistically toxic mixture of copper plus 1,2-dhATQ upregulated Cu
      Zn SOD, Mn SOD, and GR, although APX activity was downregulated. When plants were
      treated with the ROS scavenger dimethyl thiourea (DMTU), enhanced toxicity and
      formation of ROS caused by the mixture both were diminished substantially.
      However, 1,2-dhATQ toxicity was not affected significantly by DMTU. Based on this
      study, the toxicity caused by the mixture of copper plus 1,2-dhATQ directly can
      be connected to elevated levels of ROS.

PMID- 16445083
TI  - Measuring sulfide accumulation in diffusive gradients in thin films by means of
      purge and trap followed by ion-selective electrode.
AB  - A procedure for measuring in situ sulfide concentrations by coupling diffusive
      gradients in thin films (DGT) to solid-state ion-selective electrodes (ISE) is
      described and evaluated. Laboratory tests were performed to evaluate the coupling
      of these techniques, and these results were compared to the previously used
      methods of computer imaging densitometry (CID) and methylene blue. An average
      elution efficiency of 89%, as detected by ISE, was determined for a series of
      solutions containing amounts of sulfide ranging from 0.009 to 2.50 micromol. The
      validity of the standard mass-transfer equation for sulfide accumulation by DGT
      probes and subsequent detection by ISE was tested by measuring the mass of
      sulfide collected over time and with respect to varying diffusive gel
      thicknesses. Regressions of the sulfide mass accumulation versus the independent
      variables of time and inverse diffusive thickness proved to be linear. The use of
      DGT coupled to ISE provides a preconcentration method for sulfide that improves
      the detection limit (DL) over other techniques. This alternative method provides
      quantitative measurements of DGT-captured sulfide from solutions with a detection
      limit of at least 0.1 micromol/L for a 24-h deployment. The DGT technique also
      provides potential advantages in understanding sulfide speciation over existing
      methods.

PMID- 16445082
TI  - Degradation of chloropicrin in the presence of zero-valent iron.
AB  - Halonitromethanes (HNMs) are a class of halogenated disinfection byproducts
      formed upon the addition of chlorine to water containing organic matter. Batch
      experiments were performed to investigate the reaction pathways and kinetics of
      three HNMs (chloropicrin or trichloronitromethane [TCNM], dichloronitromethane
      [DCNM], and chloronitromethane [CNM]) with zero-valent iron (Fe0). All three
      compounds reacted rapidly in the presence of Fe0 (1.8-4.4 g/L) with methylamine
      (MA) as the final product. The geometric surface area-normalized rate constants
      decreased with decreasing halogenation: TCNM (301 L/[h-m2]) > DCNM (153 L/(h-m2))
      > CNM (45.9 L/[h-m2]). Nitromethane, an intermediate species, rapidly reacted to
      form MA (302 L/[h-m2]). These reactions all experienced some degree of mass
      transfer limitation (9-73%). The average carbon and chlorine mass balances for
      TCNM were >85%, indicating that the major reaction products were recovered. The
      degradation of TCNM and DCNM proceeded via the parallel reaction pathways of
      hydrogenolysis and alpha-elimination. For TCNM, 60.7 +/- 8.7% of reaction
      proceeded via hydrogenolysis and 39.3 +/- 6.4% via alpha-elimination. Knowledge
      of HNM reaction pathways and kinetics in the presence of Fe0 may be useful for
      predicting the fate of these compounds in drinking water distribution systems
      containing cast or ductile iron pipe and for developing treatment systems for HNM
      removal from water.

PMID- 16445084
TI  - A universal assay for vitellogenin in fish mucus and plasma.
AB  - Expression of vitellogenin (VTG) in male fish has become a widely used biomarker
      of exposure to environmental estrogens. Vitellogenin is usually measured in blood
      by immunoassays that require species-specific antibodies. In this paper, we
      describe a universal assay that is based on the high-molecular weight and
      extensive phosphoserine content of all VTGs. Plasma and mucosal proteins from
      Pimephales promelas and Fundulus heteroclitus and mucosal proteins from Gambusia
      holbrooki were separated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, stained with a commercially available fluropore dye (Pro-Q
      Diamond), and visualized by ultraviolet transillumination. The method allowed
      sensitive detection of VTG in females and estradiol-treated males in all species
      tested. Quantitative analysis indicated that the phosphoprotein assay is at least
      as sensitive as antibody-based methods but is universal, offering the advantage
      of VTG measurement in multiple species.

PMID- 16445085
TI  - Polychlorinated biphenyl 126 affects expression of genes involved in stress
      immune interaction in primary cultures of rainbow trout anterior kidney cells.
AB  - Stress and immune function are linked in all vertebrates, including teleost fish.
      Polychlorinated biphenyls (PCBs) are immunotoxic and impair the ability of fish
      to respond to additional stressors. In this study, we investigated the effects of
      PCB126 on stress and immune function and the interaction of these systems in fish
      using primary cultures of rainbow trout anterior kidney cells as a model. Gene
      expression levels of cytochrome P4501A (CYP1A), interleukin-1beta (IL-1beta), and
      glucocorticoid receptor (GR) were measured by real-time quantitative polymerase
      chain reaction. These genes play important roles in detoxification and immune and
      stress homeostasis, respectively. Incubation with PCB126 led to increased IL
      1beta expression between 30 min and 2 h of exposure, with expression back to
      basal levels after 6 h. Lipopolysaccharide (LPS) incubation evoked normal IL
      1beta responses after 2 and 24 h PCB incubation. Gene expression levels of GR and
      CYP1A increased in a time- and dose-dependent manner, reaching a plateau after 12
      h of incubation. Preincubation with cortisol resulted in decreased IL-1beta
      expression, increased expression of CYP1A and GR, and was accompanied by an
      abolished PCB responsiveness after more than 4 h of cortisol incubation. We
      conclude that PCB126 exposure is not "stressful," as increased cortisol levels
      would result in depressed IL-1beta expression. Incubation with PCB126 evokes a
      transient stimulation rather than permanent damage of the immune system, as LPS
      stimulation resulted in increased IL-1beta expression after PCB incubation.
      Prolonged cortisol preincubation, resembling a chronic stress paradigm,
      negatively affects the immune responsiveness of the cells as well as their
      capacity for toxicant metabolization.

PMID- 16445086
TI  - Behavioral response of Corophium volutator relative to experimental conditions,
      physical and chemical disturbances.
AB  - The preference/avoidance behavioral response of a widely used amphipod in
      toxicity tests, Corophium volutator, was investigated in relation to the presence
      of anthropogenic physical or chemical materials in sediments. Exposure
      conditions, including the density of amphipods, the depth of sediments, amount of
      overlying water, and exposure time, were examined for their influence on
      amphipods' preference for field sediments and avoidance of coarse sand. It was
      shown that these variables did not affect the response; thus, conditions similar
      to published standard toxicity tests were chosen. A gradient of sediments spiked
      with potential habitat disturbances that can be found on a beach or in
      contaminated sediments, such as those in harbors, were tested. These substances
      included sand, seaweed, burned wood, coal, crankcase oil, and diesel oil. To
      enhance the interpretation of results and decrease the variability observed when
      tests were conducted at different times over the summer, exposures were performed
      over a gradient of spike material in reference sediments. We conclude that
      physical obstacles added to reference sediments lead to less correlation with the
      behavioral response than observed with chemical interferences. Amphipods'
      behavior ranked harbor sediments similarly to previous studies concerning the
      health of intertidal mussels collected in proximity to the sediments sites. For
      five sites, preference of reference sediments was observed until the level of
      polycyclic aromatic hydrocarbons in diluted harbor sediments reached the Canadian
      Council of Ministers of the Environment sediment quality guidelines.

PMID- 16445087
TI  - Extracellular signal-regulated kinase-signaling-dependent G2/M arrest and cell
      death in murine macrophages by cadmium.
AB  - Cadmium is a nonessential heavy metal and a well-known persistent environmental
      pollutant. It causes a variety of toxic effects, including immunotoxicity. The
      exact mechanism of its cellular effects still is unclear. Cell-cycle regulation
      is an important factor that modulates cell death; however, cadmium-mediated cell
      cycle arrest leading to cell death in murine macrophages has not been
      investigated. Cadmium at 20 microM induced both apoptotic and necrotic death in
      murine macrophage (J774A.1) cultures at 24 h. Cadmium at 20 microM triggered re
      entry of G0/G1 to the next phase and increased the number of cells in the G2/M
      phase at 24 h. Phosphorylation of extracellular signal-regulated kinase (ERK)
      correlated with the cyclin-dependent kinase inhibitor p21WAF1/CIP1 induction.
      Inhibition of ERK activation by PD98059 resulted in G0/G1 arrest and partially
      released the cadmium-mediated G2/M arrest. Inhibition of ERK phosphorylation by
      PD98059 strongly attenuated cadmium-induced necrotic cell death, but did not
      prevent caspase-3 activation and DNA fragmentation. Necrosis rather than
      apoptosis was caused by cadmium-induced ERK signaling in J774A.1 cells. A
      scavenger of reactive oxygen species (ROS), N-acetylcystein, decreased cadmium
      induced ERK activation and necrotic cell death, suggesting that cadmium induces
      the ROS-ERK-p21WAF1/CIP1 signaling pathway, leading to G2/M arrest and cell
      death. These findings may be important in further understanding the cellular
      mechanisms of cadmium toxicity to provide information to assess objectively risk
      for this metal.

PMID- 16445088
TI  - Subchronic effects of methylmercury on plasma and organ biochemistries in great
      egret nestlings.
AB  - In recent years, high concentrations of mercury have been found in wading birds
      in Florida, USA. Great egret (Ardea alba) chicks (2 weeks old) were dosed orally
      daily with the equivalent of 0, 0.5, or 5 microg/g Hg as methylmercury chloride
      in the diet for up to 12 weeks. Weakness of the legs or paralysis occurred in all
      high-dosed birds. Geometric mean blood Hg concentrations were 0.17, 10.3, and
      78.5 microg/g (wet wt), respectively. Mercury concentrations for organs (microg/g
      wet wt), including brain (0.22, 3.4, and 35, respectively), liver (0.34, 15.1,
      138, respectively), and kidney (0.28, 8.1, and 120, respectively), increased in a
      dose-dependent manner. Total glutathione (GSH) peroxidase activity was
      significantly lower in the plasma, brain, liver, and kidney of the high-dosed
      group. Plasma aspartate aminotransferase activity increased with mercury
      treatment, whereas lactate dehydrogenase activity decreased. Four other plasma
      chemistries were decreased significantly in the high-dosed group and included
      uric acid, total protein, albumin, and inorganic phosphorus. Lipid peroxidation
      increased in liver (low and high dose) and brain (high dose). Tissue changes in
      concentrations of reduced thiols included decreased total thiols and protein
      bound thiols in liver, decreased protein-bound thiols in kidney, and increased
      GSH in kidney and brain. Activities of GSH S-transferase and oxidized glutathione
      reductase increased in liver. In kidney, GSH S-transferase and glucose-6
      phosphate dehydrogenase activities increased with mercury dose. These findings,
      including apparent compensatory changes, are compared to other Hg studies where
      oxidative stress was reported in egrets, herons, and diving ducks in the field
      and mallards in the laboratory.

PMID- 16445089
TI  - 4-nonylphenol-induced toxicity and apoptosis in Hydra attenuata.
AB  - Effects of 4-nonylphenol (4-NP) on the morphology and survival of the cnidarian
      Hydra attenuata were studied under acute exposure conditions. The lethal
      concentration value inducing 50% mortality after 96 h was 97.5 +/- 20 microg/L,
      whereas the lethal concentration value inducing 10% mortality after 96 h was 64
      +/- 25.5 microg/L. The no-observed-effect concentration based on morphological
      criteria was less than 25 microg/L. Hydra was one of the most sensitive
      freshwater invertebrate species behind the amphipod Hyalella azteca. Toxicity
      effects appeared rapidly and did not evolve substantially between 24 and 96 h of
      exposure. Induction of apoptosis was registered during the first hour of exposure
      to 4-NP at lethal concentrations, indicating rapid effects of the chemical.
      Abnormal increase of apoptosis may explain the acute toxicity of 4-NP in hydra.
      Results show that hydra viability is affected in the short term at 4-NP
      concentrations normally found in contaminated sites, but not at those
      concentrations reflecting lower levels of environmental contamination.

PMID- 16445090
TI  - Gene expression in caged fish as a first-tier indicator of contaminant exposure
      in streams.
AB  - The development of sensitive, biologically based indicators of contaminant
      exposure (i.e., biomarkers) is an ongoing topic of research. These indicators
      have been proposed as a first-tier method of identifying contaminant exposure.
      The primary objective of this research was to implement a biomarker-based method
      of exposure assessment using caged fish and real-time reverse-transcriptase
      polymerase chain reaction (rtRT-PCR) measurements of gene expression. Primers
      were developed for the CYPIA, metallothionein, and vitellogenin genes in rainbow
      trout (Oncorhynchyus mykiss), cutbow trout (Oncorhynchyus clarkii x mykiss), and
      Atlantic salmon (Salmo salar). Each of these genes has been shown to respond
      specifically to planar aromatic compounds, heavy metals, and environmental
      estrogens, respectively. Juvenile fish were placed in cages and exposed in situ
      at reference and contaminated sites on the Cache la Poudre River (CO, USA), the
      Arkansas River (CO, USA), the St. John River (NB, Canada), and two urban creeks
      near Dayton (OH, USA). Quantitative gene expression was determined using rtRT
      PCR. Biomarker expression profiles were obtained that demonstrated differences in
      CYPIA, metallothionein, and vitellogenin mRNA production unique to each site,
      indicating that specific types of compounds were bioavailable and present in
      sufficient concentrations to elicit transcriptional responses in the organism.
      These findings support the use of a biomarker-based approach to exposure
      identification and assessment.

PMID- 16445091
TI  - Trace metals, stable isotope ratios, and trophic relations in seabirds from the
      North Pacific Ocean.
AB  - Trace elements including mercury, cadmium, selenium, and stable nitrogen isotope
      ratios (sigma15N) were measured in tissues of Pacific seabirds. Two species of
      albatross (Diomedea immutabilis, Diomedea nigripes), four species of shearwaters
      (Puffinus bulleri, Puffinus carneipes, Puffinus griseus, Puffinus tenuirostris),
      northern fulmar (Fulmarus glacialis), and horned puffin (Fratercula corniculata)
      were collected opportunistically by an experimental fishery in the North Pacific
      Ocean. Two species each of petrels (Oceanodroma leucorhoa, Oceanodroma furcata)
      and auklets (Ptychoramphus aleuticus, Cerorhinca monocerata) were collected at
      breeding colonies on the north coast of British Columbia, Canada. Concentrations
      of toxic trace metals varied considerably among the pelagic nonbreeders; highest
      concentrations consistently were in D. nigripes (e.g., Hg), 70-fold greater than
      F. corniculata (e.g., Cd), eightfold greater than P. tenuirostris (e.g., Se), and
      fourfold greater than F. corniculata. Most essential trace elements varied little
      among species, consistent with physiological regulation. Values for sigma15N
      correlated positively with hepatic Se (r = 0.771, p = 0.025) and negatively with
      Co (r = 0.817, p = 0.013). Among the four breeding species, there were
      significant positive associations for sigma15N in muscle and hepatic Se (r =
      0.822, p = 0.002), Hg (r = 0.744, p = 0.0001), and Cd (r = 0.589, p = 0.003).
      Differences in time scales integrated by sigma15N versus trace metals in tissues
      probably reduced the apparent associations between trace-metal exposure and diet.

PMID- 16445092
TI  - Reproductive success and contaminants in tree swallows (Tachycineta bicolor)
      breeding at a wastewater treatment plant.
AB  - The uptake and effects of contaminants were measured in the insectivorous tree
      swallow (Tachycineta bicolor) at a wastewater treatment site. The study examined
      reproductive, immunological, and growth endpoints in tree swallows exposed to
      chlorinated hydrocarbon contaminants and to 4-nonylphenol in wastewater lagoons
      at the Iona Wastewater Treatment Plant, Vancouver (BC, Canada). Clutch size was
      significantly lower in tree swallows breeding at Iona Island in 2000 and 2001
      compared to the reference site. In 2000, fledging success was significantly lower
      and mean mass of nestling livers was significantly higher in the tree swallows
      breeding at the Iona Island Wastewater Treatment Plant. Additional factors that
      may influence reproductive success, such as parental provisioning and diet
      composition, did not differ significantly between sites. Levels of 4-nonylphenol
      detected in sediment and insects were elevated at the Iona Island Wastewater
      Treatment Plant (2000: lagoon sediment 82,000 ng/g dry wt, insects 310 ng/g wet
      wt; 2001: lagoon sediment 383,900 ng/g dry wt, insects 156 ng/g wet wt) compared
      to the reference site (2000: pond sediment 1,100 ng/g dry wt, insects not
      sampled; 2001: pond sediment 642 ng/g dry wt, insects 98 ng/g wet wt). These
      results indicate that tree swallows might be a useful indicator species for
      exposure to 4-nonylphenol at wastewater treatment sites: however, further work is
      necessary to determine the extent of uptake and effects of 4-nonylphenol in
      riparian insectivorous birds.

PMID- 16445093
TI  - Effect of temperature on toxicity of a natural pyrethrin pesticide to green anole
      lizards (Anolis carolinensis).
AB  - Metabolic rates of reptiles vary with body temperature; therefore, the
      sensitivity of reptiles to a particular dose level of a pesticide might be
      expected to vary as well. The purpose of the present study was twofold: To
      evaluate the effects of temperature on the toxicity to green anole lizards
      (Anolis carolinensis) of a single concentration of a natural pyrethrin pesticide
      via percutaneous exposure, and to compare the effects of temperature (20 vs 35
      degrees C) on the toxicity of different concentrations of pyrethrins to green
      anoles. When lizards were exposed to a solution that contained 300 mg/L of
      pyrethrins, the mortality of lizards maintained at 15 and 20 degrees C was
      significantly higher (p < 0.01) than the mortality of lizards maintained at 35
      and 38 degrees C. In addition, the median lethal concentrations of pyrethrins for
      lizards maintained at 20 and 35 degrees C were 77.6 and greater than 300 mg/L,
      respectively. Therefore, temperature clearly influenced the sensitivity of
      lizards to pyrethrin pesticides.

PMID- 16445094
TI  - A comparison of the lethal and sublethal toxicity of organic chemical mixtures to
      the fathead minnow (Pimephales promelas).
AB  - The joint toxic effects of known binary and multiple organic chemical mixtures to
      the fathead minnow (Pimephales promelas) were defined at both the 96-h 50% lethal
      effect concentration (LC50) and sublethal (32-d growth) response levels for
      toxicants with a narcosis I, narcosis II, or uncoupler of oxidative
      phosphoralation mode of toxic action. Experiments were designed to define the
      degree of additive joint toxicity for mixtures of specific xenobiotics that are
      believed to act through a similar or different primary mode of toxic action. Our
      results support the general conclusion that concentration addition is expected
      for the joint toxicity of similarly acting toxicants. When chemicals were thought
      to act by a dissimilar mechanism, the combined effects we observed at both of the
      response levels tested were less than predicted by concentration addition, but
      usually more toxic than that predicted by the independent action/response
      addition model. It was demonstrated in multichemical mixtures that several
      toxicants can act together in a nearly additive fashion to produce effects even
      when they are present at concentrations below their individual no-observed-effect
      concentration. Concentration-response relationships for test chemicals at both
      the lethal and sublethal responses were defined for each of the three modes of
      toxic action studied. When normalized for potency, it was observed that one
      relationship could be defined to predict lethality to juvenile fathead minnows
      when exposed to individual chemicals with either a narcosis I, narcosis II, or
      uncoupler mode of toxic action. These sublethal relationships were similar for
      the narcosis I and narcosis II test chemicals, but a steeper response was
      observed for tests conducted with uncouplers.

PMID- 16445095
TI  - Polychlorinated biphenyls and toxaphene in preferred prey fish of coastal
      southeastern U.S. bottlenose dolphins (Tursiops truncatus).
AB  - Legacy organochlorine (OC) contaminants continue to pose a potential risk to
      ecological and human health in coastal aquatic ecosystems of the southeastern
      United States. Polychlorinated biphenyls (PCBs) and toxaphene (TOX) were analyzed
      by gas chromatography with electron capture detection and negative chemical
      ionization mass spectrometry in 77 composites of four inshore fish species
      commonly preyed upon by bottlenose dolphins (Tursiops truncatus) from estuaries
      near Savannah, Georgia (SAV), Brunswick, Georgia (BRN), and Jacksonville, Florida
      (JAX), USA. Whereas seasonal and species-specific differences were minimal,
      differences among mean total PCB concentrations (sigmaPCBs) by estuary (42.0 +/-
      48.3, 1.59 +/- 1.24, and 0.281 +/- 0.075 microg/g lipid for BRN, JAX, and SAV,
      respectively) were highly significant. This estuary-specific trend also held true
      for mean total toxaphene concentrations (sigmaTOX): 49 +/- 100 (BRN), 1.2 +/-
      0.52 (JAX), and 0.40 +/- 0.19 microg/g lipid (SAV). Congener profiles of PCBs
      also were found to be significantly different among estuaries, with BRN and (to a
      lesser extent) JAX samples enriched with highly chlorinated homologs associated
      with Aroclor 1268, a legacy OC linked to a historical point source in Brunswick.
      The observed spatial heterogeneity in OC concentrations and PCB congener profiles
      suggests that contaminated fish from Brunswick pose the greatest risk to
      ecological and human health via biomagnification and seafood consumption; highly
      chlorinated PCBs (and possibly toxaphene) are transported in a southerly,
      alongshore direction; and the uniqueness of Aroclor 1268 underscores its utility
      as a signature proxy in future regional ecotoxicological studies.

PMID- 16445096
TI  - Effects of selected biocides used in the disinfection of cooling towers on
      toxicity and bioaccumulation in Artemia larvae.
AB  - This paper reports the acute toxicity of three biocides used in the disinfection
      of cooling towers, tetrakis(hydroxymethyl) phosphonium chloride (THPC),
      trichloroisocyanuric acid (TCIC), and sodium bromide (NaBr), on Artemia larvae,
      their effect on the phototactic response of this organism, and the potential of
      bioaccumulation in this species. The 24-h median lethal concentration (LC50)
      values for these biocides with respect to 24-, 48-, and 72-h-old Artemia,
      determined by static bioassays, showed the following rank order of toxicity: THPC
      < TCIC < NaBr. An age-dependent increase in sensitivity was seen for each
      compound. All three biocides reduced the phototactic response of 24-h-old Artemia
      larvae in 24-h static bioassays; the median inhibitory concentration ratios
      obtained were 30 to 40 times lower than their respective 24-h LC50 values. The
      results suggest that phototaxis bioassays could provide the speed and simplicity
      required for screening many potential pollutants for harmful effects. The
      bioconcentration factors obtained for Artemia larvae exposed to 10% LC50 for 168
      h in renewal assays were 93.75, 1.67, and 0.23 for THPC, TCIC, and NaBr,
      respectively. This shows these biocides pose no bioaccumulation risk in this
      organism, although the value of 93.75 obtained for THPC is close to the threshold
      above which such a risk is considered to exist.

PMID- 16445097
TI  - Light as a confounding factor for toxicity assessment of complex contaminated
      sediments.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are contaminants often found in
      sediments. Their relevant contribution to toxic effects induced by environmental
      samples has been demonstrated using effect-directed analysis (EDA). Toxicity of
      PAHs previously has been reported to depend on light conditions. The aim of this
      study was to analyze the influence of simulated sunlight, in comparison to
      standard algal growth light, on the toxicity of samples, in which PAHs were
      identified as major toxicants using EDA. Additionally, toxicity of identified
      toxicants and mixtures of these compounds were assessed. It can be shown that the
      samples, the PAH compounds, and the created mixtures exhibit photoenhanced
      toxicity. The combined effects of the mixtures can be predicted using the model
      of concentration addition. This is surprising because different modes of action
      have been reported to contribute to phototoxicity of the identified toxicants.
      For the confirmation step in EDA, the toxicity assessment under simulated
      sunlight reveals that less of the samples' toxicity can be explained by the
      identified compounds, compared to the assessment conducted under standard growth
      light. Finally, the relevance of light conditions in the toxicity assessment is
      demonstrated for eight out of 13 transect samples of sediment extracts from river
      Elbe, Germany.

PMID- 16445098
TI  - Air-vegetation partitioning of polychlorinated biphenyls near a point source.
AB  - We investigated polychlorinated biphenyl (PCB) emissions to the environment from
      a waste treatment and transfer facility over the course of three years. We show
      that the facility, which undertakes PCB waste consolidation and maintains a low
      yield incinerator for products such as light ballasts, acted as a point source
      for the spatial distribution of PCBs in vegetation. Concurrent air and vegetation
      sampling was performed to study the relationship between air-vegetation
      partitioning and the octanol-air partition coefficient (KOA). We show evidence of
      equilibrium partitioning for lower-chlorinated congeners (log KOA between 7 and
      8.5), kinetically limited deposition on plants for intermediate congeners (log
      KOA between 8.5 and 11), and particle-bound deposition for congeners with high
      log KOA values (> 11), consistent with the McLachlan partitioning model. From
      spring to autumn, heavier congeners become much more concentrated in samples
      farther away from the facility, possibly because of higher temperatures, which
      enhance dispersal of these congeners. Multivariate principal components analysis
      showed that PCB composition in vegetation near the emission source most closely
      resembled the Aroclor mixtures processed by the treatment facility.

PMID- 16445099
TI  - Spatial, temporal, and dietary determinants of organic contaminants in nestling
      tree swallows in Point Pelee National Park, Ontario, Canada.
AB  - Point Pelee National Park of Canada in southwestern Ontario, an important
      migratory route and vital breeding area for many birds, has localized areas of
      organochlorine (OC) pesticide contamination from agricultural production during
      the 1950s and 1960s. During 2001 and 2002, we investigated movement of persistent
      contaminants through the food web with the insectivorous tree swallow
      (Tachycineta bicolor) as a sentinel. The a priori site classifications,
      contaminated or reference, were based on soil residues of
      dichlorodiphenyltrichloroethane (DDT) and its breakdown products (sigmaDDT),
      dieldrin, and other OC pesticides. In 2001, all nestling tissue samples were
      pooled by site, and residue levels did not reflect the soil contaminant status.
      To improve sampling accuracy in 2002, tissue residues were determined from birds
      in individual nests. This showed OC pesticides to be higher in samples from
      contaminated sites compared with reference sites (p = 0.031). Polychlorinated
      biphenyls (PCBs), which were not detected in soil samples, were present in the
      nestlings and were not related to site of origin (p = 0.422). In 2002, dietary
      samples were collected from nestlings and identified to taxon, and representative
      insects collected from nesting sites were analyzed for PCBs and other OCs.
      Consumption of terrestrial prey was positively correlated with tissue residues of
      sigmaDDT (p = 0.006), whereas PCBs came from aquatic prey, Hexagenia mayflies (p
      = 0.003). Dietary details proved valuable in this study of contaminant transfer
      in insectivorous vertebrates.

PMID- 16445100
TI  - Improved empirical models describing hormesis.
AB  - During the past two decades, the phenomenon of hormesis has gained increased
      recognition. To promote research in hormesis, a sound statistical quantification
      of important parameters, such as the level and significance of the increase in
      response and the range of concentration where it occurs, is strongly needed.
      Here, we present an improved statistical model to describe hormetic dose-response
      curves and test for the presence of hormesis. Using the delta method and freely
      available software, any percentage effect dose or concentration can be derived
      with its associated standard errors. Likewise, the maximal response can be
      extracted and the growth stimulation calculated. The new model was tested on
      macrophyte data from multiple-species experiments and on laboratory data of Lemna
      minor. For the 51 curves tested, significant hormesis was detected in 18 curves,
      and for another 17 curves, the hormesis model described that data better than the
      logistic model did. The increase in response ranged from 5 to 109%. The growth
      stimulation occurred at an average dose somewhere between zero and concentrations
      corresponding to approximately 20 to 25% of the median effective concentration
      (EC50). Testing the same data with the hormesis model proposed by Brain and
      Cousens in 1989, we found no significant hormesis. Consequently, the new model is
      shown to be far more robust than previous models, both in terms of variation in
      data and in terms of describing hormetic effects ranging from small effects of a
      10% increase in response up to effects of an almost 100% increase in response.

PMID- 16445102
TI  - MA redux: will private plans come back to capitation?

PMID- 16445101
TI  - Comparative sediment quality guideline performance for predicting sediment
      toxicity in southern California, USA.
AB  - Several types of sediment quality guidelines (SQGs) are used by multiple agencies
      in southern California (USA) to interpret sediment chemistry data, yet little
      information is available to identify the best approaches to use. The objective of
      this study was to evaluate the predictive ability of five SQGs to predict the
      presence and absence of sediment toxicity in coastal southern California: the
      effects range-median quotient (ERMq), consensus moderate effect concentration
      (consensus MEC), mean sediment quality guideline quotient (SQGQ1), apparent
      effects threshold (AET), and equilibrium partitioning (EqP) for organics. Large
      differences in predictive ability among the SQGs were obtained when each approach
      was applied to the same southern California data set. Sediment quality guidelines
      that performed well in identifying nontoxic samples were not necessarily the best
      predictors of toxicity. In general, the mean ERMq, SQGQ1q, and consensus MECq
      approaches had a better overall predictive ability than the AET and EqP for
      organics approaches. In addition to evaluating the predictive ability of SQGs
      addressing chemical mixtures, the effect of an individual SQG value (DDT) was
      also evaluated for the mean ERMq with and without DDT. The mean ERMq without DDT
      had a better ability to predict toxic samples than the mean ERMq with DDT.
      Similarities in discriminatory ability between different approaches, variations
      in accuracy among SQG values for some chemicals, and the presence of complex
      mixtures of contaminants in most samples underscore the need to apply SQGs in
      combination, such as the mean quotient. Management objectives and SQG predictive
      ability using regional data should be determined beforehand so that the most
      appropriate SQG approach and critical values can be identified for specific
      applications.

PMID- 16445103
TI  - Health plan data reveal insights into PMPM rates, utilization trends.

PMID- 16445104
TI  - Do disease management programs really save money?

PMID- 16445105
TI  - Find untapped savings by adopting higher generic prescribing patterns.

PMID- 16445107
TI  - Transform your organization into a five-star service provider.

PMID- 16445106
TI  - Six sigma: it's real, it's datadriven, and it's here.

PMID- 16445108
TI  - GP commissioning 'bribe' will 'sink' policy before it begins.

PMID- 16445109
TI  - Soaring energy costs hit trusts.

PMID- 16445110
TI  - The year ahead. Vive la resolution.

PMID- 16445111
TI  - On listening to patients.

PMID- 16445112
TI  - Barometer. PCTs Dec 2005.

PMID- 16445113
TI  - Incapacity benefit. Back to basics.
AB  - Long periods on incapacity benefits lead to declining health and greater cost to
      the NHS. Possible moves to cut numbers on benefits include moving people who
      could be treated in other ways off urghery waiting sercvices.

PMID- 16445114
TI  - Editorial overview: safety of drugs can never be absolute.

PMID- 16445115
TI  - Computational toxicology: heading toward more relevance in drug discovery and
      development.
AB  - Computational tools for predicting toxicity have been envisioned to have the
      potential to broadly impact the attrition rate of compounds in early research and
      development, and prove successful in predicting adverse drug reactions (ADRs) in
      patients enrolled in clinical trials, and particularly prior to the marketing of
      drugs. The impact of such tools to date, however, has been modest and relatively
      narrow in scope. It is important to note that advances within medical science and
      newer approaches in clinical development will require predictive toxicology
      applications to be viable, and therefore efforts must be directed into making
      these tools relevant to the goal of preventing undesired toxicity in patients. In
      this Editorial Opinion, the current status of computational toxicology within
      industry is reviewed and areas in which advances can be made are highlighted.
      While predicting the potential of a compound to induce specific ADRs continues to
      be a formidable task, the field of computational biology is now heading in a
      direction more relevant to human disease and adverse outcomes.

PMID- 16445116
TI  - Drug withdrawals and the lessons within.
AB  - Drug withdrawals over recent decades have triggered changes in the way that drug
      targets and screening programs are researched and designed. In the cases having
      the greatest impact, the reason for withdrawal was the reversible interaction of
      a drug or its metabolite with a single receptor, ion channel or enzyme (primary
      or secondary pharmacology). Once this interaction is identified, screens can be
      established and validated. When the mechanism is complex (eg, organ toxicity),
      however, such screens are difficult to implement and usually examine only the
      initial step, leading to considerable problems in extrapolation and risk
      definition. This review classifies drugs withdrawn from the US market over the
      last 25 years by their reasons for withdrawal, and examines how drug discovery
      programs have been modified in response to these events.

PMID- 16445117
TI  - Screening for reactive intermediates and toxicity assessment in drug discovery.
AB  - Moving forward in the 21st century, toxicity remains a significant cause for
      failures during drug development, and limited correlations exist between
      preclinical in vitro cellular toxicity and/or in vivo animal toxicity models, and
      human toxicity. This is due, in part, to the fact that drug candidates generally
      target multiple tissues rather than single organs, and result in a series of
      inter-related biochemical events. Drug-induced toxicities, such as idiosyncratic
      drug reactions, represent a serious complication of drug therapy that needs to be
      addressed at the drug discovery stage. Many robust toxicity screening methods,
      however, have been developed, and are described in the literature. Although
      biochemical mechanisms of drug-induced toxicities are complex, by combining these
      screening methods into a panel of assays, a risk assessment profile/decision
      making guide can be obtained for each drug candidate. The panel of assays covered
      by this review broadly includes in silico prediction of reactive intermediates,
      detection and structural characterization of reactive intermediates, covalent
      binding of reactive intermediates to macromolecules, and the impact of reactive
      intermediates on cellular functions. Current and future strategies for the proper
      sequencing of these assays in a drug discovery environment are also discussed.

PMID- 16445118
TI  - The impact of recent innovations in the use of liquid chromatography-mass
      spectrometry in support of drug metabolism studies: are we all the way there yet?
AB  - Absorption, distribution, metabolism, excretion and toxicology (ADMET) studies
      are widely used in drug discovery and development to help obtain the optimal
      balance of properties necessary to convert lead compounds into drugs that are
      safe and effective for human use. Drug discovery efforts have been aimed at
      identifying and addressing metabolism issues at the earliest possible stage, by
      developing and applying innovative liquid chromatography-mass spectrometry (LC
      MS)-based techniques and instrumentation, which are both faster and more accurate
      than prior techniques. Such new approaches are demonstrating considerable
      potential to improve the overall safety profile of drug candidates throughout the
      drug discovery and development process. These emerging techniques streamline and
      accelerate the process by eliminating potentially harmful candidates earlier and
      improving the safety of new drugs. In the area of drug metabolism, for example,
      revolutionary changes have been achieved by the combination of LC-MS with
      innovative instrumentation such as triple quadrupoles, ion traps and time-of
      flight mass spectrometry. In turn, most ADMET studies have come to rely on LC-MS
      for the analysis of an ever-increasing workload of potential candidates. This
      article provides a discussion on the importance of LC-MS in supporting drug
      metabolism studies, and highlights the relative merits of current applications
      for LC-MS in drug metabolism testing and analysis. These applications include in
      vitro and in vivo testing, pharmacokinetic profiling, chiral separations, stable
      isotope labeling, metabolic activation testing, metabolite characterization and
      radiolabeled-drug testing.

PMID- 16445119
TI  - Informed toxicity assessment in drug discovery: systems-based toxicology.
AB  - Technological advances in the biological, chemical and in silico sciences have
      transformed many scientific disciplines, including toxicology. A vast new palate
      of toxicity testing tools is now available to investigators, enabling the
      generation of enormous amounts of data using only small amounts of test sample
      and at relatively low cost. In addition to these tools, the pharmaceutical
      industry has an urgent need for toxicity testing earlier in the process, based on
      the recognition that safety issues are the single largest cause of drug candidate
      attrition from development portfolios and the marketplace. However, along with
      the opportunity provided by new testing tools comes the dilemma of deciding which
      tools to use and, equally as important, when and why to use them. It may well be
      unwise to apply a new toxicity test or screening system simply because one can,
      as both false positive and false negative outcomes can quickly negate the value
      of a toxicity test system and may even have a net negative impact on drug
      discovery productivity. This can be true even of test systems that are considered
      to be 'validated' in the traditional sense. How then is an investigator or drug
      discovery organization to decide which of the new tools to use, and when to use
      them? Proposed herein is a strategy for identifying high-value toxicity testing
      systems and strategies based on program knowledge and informed decision-making.
      The decision to apply a certain toxicity testing system in this strategy is
      informed by knowledge of the pharmacological target, the chemical features of
      molecules active at the pharmacological target, and existing public domain or
      institutional learning. This 'fit-for-purpose' approach limits non-targeted or
      'uninformed' toxicity screening to only those few test systems with high
      specificity, strong outcome concordance and molecular relevance to frequently
      encountered toxicity risks (eg, genotoxicity). Additional toxicity testing and
      screening is then conducted to address specific known or potential toxicity
      risks, based on existing knowledge of the target pharmacology and secondary
      pharmacology or chemical attributes with known or suspect risk, and by active
      'interrogation' of both the target and active chemical moieties during the drug
      discovery process. This model for toxicity testing decision-making is illustrated
      by two case studies from recent experience.

PMID- 16445120
TI  - The state-of-the-art in predictive toxicogenomics.
AB  - Predictive toxicogenomics, ie, the acquisition of advanced knowledge of the
      safety profile of a compound using genomic biomarkers, is a technology that
      provides much optimism for improving early drug discovery decisions.
      Toxicogenomics creates an opportunity to shift attrition to earlier stages in
      drug development to a point where course-corrective action can be taken with
      relatively lower financial costs, thus improving the efficiency of the drug
      development process. This review will survey the current state-of-the-art in
      toxicogenomics for predicting toxicity, both in vivo and in vitro, with emphasis
      on the use of classification algorithms and the importance of toxicogenomic
      databases for biomarker discovery and validation.

PMID- 16445121
TI  - Integration of genomic and metabonomic data in systems biology--are we 'there'
      yet?
AB  - The measurement of genes, proteins and metabolites has gained increasing
      acceptance as a means by which to study the response of an organism to stimuli,
      whether they are environmental, genetic, pharmacological, toxicological, etc.
      Typically referred to as genomics, proteomics, and metabonomics or metabolomics,
      respectively, these methods as independent entities have undoubtedly provided new
      biological insight that was not attainable a decade ago. Not surprisingly,
      scientists continue to push the boundaries to extract knowledge from data, and it
      is currently recognized that the full realization of these technologies is
      limited by a lack of tools to enable data integration. Integration of these 'omic
      datasets, or integromics, is desirable as it links the individual biological
      elements together to provide a more complete understanding of dynamic biological
      processes. Accordingly, in addition to developing new data analysis methods to
      extract further details from each of the high-content datasets individually,
      effort is also being expended to create or improve statistical methods,
      databases, annotations and pathway mapping to maximize our learning. There are
      several recent examples, in both mammalian and non-mammalian systems, in which
      genes, proteins and/or metabolites have been integrated using either biology- or
      data-driven strategies. Herein, key findings are reviewed, gaps in our current
      tools and technologies are identified and illustrated, and perspective is
      provided on the potential of integromics in biological research.

PMID- 16445122
TI  - The complexities inherent in attempts to decrease drug clearance by blocking
      sites of CYP-mediated metabolism.
AB  - Oxidative metabolism by the cytochromes P450 (CYPs) is the most common metabolic
      pathway of drug clearance. Medicinal chemists in drug discovery often synthesize
      analogs of lead molecules to reduce clearance due to metabolism. One method
      generally used when attempting to reduce CYP metabolism is to identify the site
      of modification to 'block' it. Substituting fluorine in the place of hydrogen at
      metabolically labile positions, for example, is a common approach, although
      deuterium can also be considered here for simplicity. In this case, the rate of
      metabolism via a specific pathway is attenuated, but the rate of overall
      substrate consumption or overall clearance is not significantly altered, due to a
      compensatory increase in the rate of formation of an alternate metabolite. The
      concepts and evidence behind this phenomenon as it relates to complexities in
      blocking metabolic clearance are presented herein.

PMID- 16445123
TI  - Bringing primary cells to mainstream drug development and drug testing.
AB  - Although cell-based screening is already an essential tool in drug discovery, the
      cell models currently available are fast becoming inadequate. The use of
      transformed cells as models in almost every step of the discovery pipeline needs
      to be substituted with more relevant, disease-oriented models, and the use of
      patient-derived primary cells should logically become the next best strategy. In
      the past the use of such cells has been restricted by their scarcity and
      difficulty in manipulation and general handling; however, recent advances in
      isolation and growth, as well as assay miniaturization, transfection efficiency
      and assay sensitivity, have enabled their use in the mainstream of drug
      discovery. This review explores some of these enabling technologies, as well as
      some of the most critical uses of primary cells that may dramatically alter the
      landscape of drug discovery and drug testing.

PMID- 16445124
TI  - Drug development and hormesis: changing conceptual understanding of the dose
      response creates new challenges and opportunities for more effective drugs.
AB  - This review proposes that the emerging acceptance of the hormetic dose-response
      model in toxicology and pharmacology has the potential to significantly change
      important aspects of drug development. Two situations where the hormesis concept
      may affect drug development are considered: one in which low-dose stimulation may
      represent an adverse/unwanted effect (eg, stimulation of tumor cell proliferation
      by antitumor drugs), the other in which low-dose stimulation defines the
      therapeutic zone (ie, a beneficial or intended effect; eg, cognition enhancement
      in Alzheimer's disease treatment). Examples are used to demonstrate that the
      hormetic dose-response model has implications for the definition of an ideal
      candidate for a therapeutic agent, as well as implications for study designs
      needed to assess the quantitative features of the dose-response relationship.

PMID- 16445125
TI  - Landscape of current toxicity databases and database standards.
AB  - Having readily available historical information for modeling toxicity has become
      important throughout the various stages of research and development. The high
      cost of late-phase attrition and recent international regulatory legislations
      have made even more acute the need to be able to mine the fragmented data and
      information available across diverse databases. In addition, the general trend to
      accelerate regulatory processes globally makes the effective use of existing data
      an imperative. To achieve efficient screening, develop profiles and gain the
      ability to cross reference, databases must be interoperated to allow data
      exchange and integration. Several database standards and controlled vocabulary
      initiatives have been used in the development of toxicity data models to
      transform the current landscape. This review describes the major databases of
      toxicological information now available, and provides a simple example of
      standardization that demonstrates the benefits of a toxicity database containing
      such qualified data.

PMID- 16445126
TI  - [Antibody response to Ascaris lumbricoides among the children population in the
      Usti Region].
AB  - A group of 156 children aged between 10 and 12 years were screened for IgG and
      IgE antibodies to Ascaris lumbricoides. The study subjects were 64 children of
      Romany origin and 92 children from the majority population. IgG antibodies to
      Ascaris lumbricoides were detected in 112 (71.8%) children. No difference in the
      prevalence of IgG antibodies was found between Romany children and those from the
      majority population. As many as 34.1% of the study subjects had IgE antibodies to
      Ascaris lumbricoides, again with no difference between the two ethnic groups.
      Children with IgG antibodies to Ascaris lumbricoides had significantly higher
      total IgE levels compared to those who had tested IgG negative. To demonstrate
      induction of a non-specific IgE response was one of the study objectives. The
      high prevalence rates of IgG and IgE antibodies to Ascaris lumbricoides are
      suggestive of a high frequency of cross- and non-specific reactions. Possible
      effect of cross-reactivity to other antigens on the specific IgG and IgE antibody
      response to Ascaris lumbricoides is discussed.

PMID- 16445127
TI  - [Biological characteristics of Plesiomonas shigelloides strains of human and
      animal origin].
AB  - We focused on serotyping and biological characteristics of Plesiomonas
      shigelloides strains potentially associated with virulence. Thirteen strains
      isolated from humans (H) and 14 strains of animal origin (A) were tested. The
      most frequent serotype among H strains was 040:H6 while 066:H3 predominated among
      A strains. All of the H strains and 92.8% of A strains were hydrophobic. H
      isolates showed lower motility (30.1 mm) compared to A isolates (46.8 mm). As
      many as 76.9% and 71.4% of H and A strains, respectively, produced beta
      hemolysis. Both H and A strains exhibited low biofilm production on a glass
      surface. No significant differences were found between H and A strains in lipase
      production and histidine decarboxylase production. The zones of bacterial growth
      inhibition in response to oxidative stress were on average 26.6 mm and 28.1 mm
      for H and A strains, respectively. None of the strains tested produced
      unsubstituted short-chain acyl homoserine lactones. Our results showed that
      tested Plesiomonas shigelloides strains produced multiple potential virulence
      factors that may play a role in the pathogenesis of infections caused by this
      agent.

PMID- 16445129
TI  - [Foams as disinfectant carriers].
AB  - The article deals with surfactants capable of forming an aerodispersive system,
      foam, under specific conditions as described below. Characteristics of
      surfactants usable as foaming agents are specified. Attention is paid to
      detergency and detergent effects of foams, wetting process, dispersion formation,
      stabilization of foams and stabilizers. Rheological properties of foams, more
      precisely volume increase and stability, are described. Methods for disinfection
      efficacy testing of foaming agents are presented. Advantages and disadvantages of
      using foams for disinfection are summarized: it is concluded that the use of
      foams in disinfection is universally advantageous and means a great advance in
      disinfection technology.

PMID- 16445128
TI  - [Mortality of drug users. Summary of cohort study results].
AB  - AIMS: The cohort study aimed to find the level of mortality among different
      groups (cohorts) of drug users and compare it with the mortality rate of the
      general population. At the same time, the study focused on differences in
      mortality levels according to gender and type of drug used. METHODS: A
      retrospective cohort mortality study was conducted. In 1997-2002, 4 defined
      groups of drug users were followed. These included two cohorts of hospitalized
      persons for drug-related behavioral disorders (12,207 and 2,824 persons), cohort
      of injecting drug users with reported viral hepatitis (3,037 persons) and
      substitution treatment clients (704 persons). FINDINGS: Direct standardized
      mortality rate reached 16-33 per 1000 person-years of follow-up, depending on the
      cohort. In all cohorts, mortality was higher among men than women. In the follow
      up period, mortality observed a consecutive decrease. The level of mortality
      among drug users was 8-11 times higher compared to general population. The
      highest mortality was observed for polyvalent and opiate users, relatively lowest
      for stimulants users. CONCLUSIONS: The level of mortality of drug users in the
      Czech Republic is comparable to mortality in other European countries; compared
      to other cohorts, the mortality level in CR is relatively lower. The study proved
      differences in mortality levels by cohorts; further research should focus on the
      impact of treatment on the mortality levels.

PMID- 16445130
TI  - [Memories of a cholera epidemic. Part 2].

PMID- 16445131
TI  - [Whipple's disease/Morbus Whipple. Main symptoms: fever, lymphadenopathy,
      arthralgia, weight loss, chronic diarrhea].

PMID- 16445132
TI  - [What is your diagnosis? Rectus sheath hematoma].

PMID- 16445133
TI  - [Disease and therapy in Thomas Mann].

PMID- 16445134
TI  - [Doctors in the work of Thomas Mann].

PMID- 16445135
TI  - [Thomas Mann as patient].

PMID- 16445136
TI  - [Thomas Mann's fascination of death from a physicians's view].

PMID- 16445138
TI  - Second opinions on the prevention of caesarean sections.

PMID- 16445137
TI  - Medical manpower: poorer countries are being exploited.

PMID- 16445139
TI  - Avian influenza and the risk to human health.

PMID- 16445140
TI  - Asthma control and management: a patient's perspective.
AB  - Irish asthma guidelines, published in 2000, are based on the Global Initiative
      for Asthma (GINA) international asthma management guidelines and provide
      recommendations for optimal asthma management and control. Using the same
      methodology as employed in the Asthma Insights and Reality in Europe (AIRE)
      survey, which assessed whether specific goals of asthma management based on GINA
      were being realised, 400 patients with current asthma in Ireland were interviewed
      in the Asthma Insights and Reality in Ireland (AIRI) survey to determine their
      healthcare utilisation, symptom severity, activity limitations and level of
      asthma control. Of those surveyed, acute services were utilised by a significant
      number of respondents. Over the previous year, 27% had either an emergency visit
      to the hospital or their general practitioner (GP) and 7% were hospitalised for
      asthma. In terms of asthma control, 19% experienced sleep disturbance at least
      once a week, 29% missed work or school and 37% of respondents experienced
      symptoms during physical activity over the previous 4-week period. Based on these
      findings, the level of asthma control and asthma management in Ireland falls
      short of recommended national and international asthma guidelines.

PMID- 16445142
TI  - Lymphocytic meningitis: incidence, causes and outcomes over five years.
AB  - Over a five-year period 114 cases of lymphocytic meningitis were admitted to a
      general hospital. Case notes were reviewed to determine incidence, causes and
      outcomes and to identify what clinical features, cerebrospinal fluid (CSF)
      parameters or other tests were useful in elucidating a cause. Of 114 patients
      with lymphocytic meningitis 44 had viral meningitis, six viral encephalitis, and
      seven had other infective meningo-encephalitis. Seven patients had carcinomatous
      meningitis, nine had an autoimmune/inflammatory process, thirteen had a
      demyelinating central nervous system (CNS) disorder, and two had an inflammatory
      neuropathy. In 26 patients no diagnosis was reached. Six of these showed clear
      steroid responsiveness. Overall lymphocytic meningitis had a good prognosis.
      Clinical and CSF characteristics were important in diagnosis and prognosis.
      Recommendations on management of these cases are presented.

PMID- 16445141
TI  - Heart transplant candidates: factors influencing waiting list mortality.
AB  - Cardiac transplantation is a successful treatment for end-stage heart disease.
      However the number of potential candidates is significantly greater then number
      of suitable organ donors. We reviewed the characteristics of new transplant
      candidates presenting for assessment for cardiac transplantation to the Irish
      Heart & Lung Transplant programme over a one year period. Of 44 patients referred
      for assessment, 24 (54.5%) were listed for cardiac transplantation. Six have died
      while awaiting transplantation, seven have been transplanted and eleven remain on
      the active transplant list. The six month survival rate on the transplant waiting
      list is 74%. Although the Irish system of organ donation has traditionally
      provided high organ donation rates in comparison with other countries, the demand
      for suitable heart donors exceeds supply. Newer methods of promoting and
      facilitating organ donation may prove beneficial in improving the number of
      donations and addressing the long waiting time for cardiac transplantation.

PMID- 16445143
TI  - Knowledge of statistical methods and their implications for clinical practice: a
      survey of paediatricians.
AB  - Improvements in computer software have contributed to an increase in the use of
      multivariate statistical analyses e.g. multipLe regression in recent times. Our
      aim was to assess the familiarity with, and understanding of these complex
      statistical methods among Irish paediatricians. Questionnaires were sent to all
      paediatric specialist registrars (SpRs) and consultants in the Republic of
      Ireland. The questionnaire detailed information about clinical practice, and
      contained a short quiz on statistical methods. 137 questionnaires were
      distributed, and 62 (45.6%) were returned. Eighty four percent of respondents
      aimed to read journals weekly but only 46.7% managed to. The commonest journals
      used were; Archives of Disease in Childhood (93%), Pediatrics (53%), British
      Medical Journal (46%) and Journal of Paediatrics (45%). 28 of 61 (45.9%) of
      respondents have had further training in statistics. Only 19% felt they had a
      clear understanding of regression. Fifty-eight of 62 respondents (93.5%)
      completed the short test. The average score was 5.1/10. Sixty seven percent of
      questions on basics were answered correctly, 37.9% of questions on application of
      tests were answered correctly and 25.8% of questions on regression were answered
      correctly. Only 3.4% answered all questions on regression correctly. The overall
      knowledge of advanced statistical methods was poor. There is a poor overall
      understanding of the concept of regression, despite its increasingly common use.

PMID- 16445144
TI  - Tonsillectomy--cold dissection vs. hot dissection: a prospective study.
AB  - Throughout the years, investigators and surgeons have developed new techniques
      for tonsillectomy aiming to lessen the postoperative morbidity and complications
      of tonsillectomy. It is generally accepted that the ideal method should decrease
      operative time, blood loss, postoperative haemorrhage and morbidity. To compare
      the technique and post-operative morbidity of two different tonsillectomy
      methods: cold dissection and bipolar electrodissection. A prospective study
      including a total of 545 children (Age: 3-16 yrs) undergoing tonsillectomy at The
      Children's University Hospital in Dublin, Ireland, from January 2003 to December
      2003. The incidence of primary, secondary haemorrhage and postoperative pain was
      compared between both techniques. The overall rate of haemorrhage was 3.6% (20
      patients) this included primary haemorrhage in 0.3% (2 patients) and secondary
      haemorrhage in 3.3% (18 patents). Primary haemorrhage occurred only in the
      electrodissection technique. As regards to secondary haemorrhage it was higher in
      the electrodissection technique 2.3% (12 patients) compared to 1% (6 patients) of
      the cold dissection technique. Patients rated pain to be more severe in the
      electrodissection technique compared to the cold dissection technique. Cold
      dissection tonsillectomy technique is still considered to be a safe and effective
      method with less posoperative morbidity complications as evidenced from our
      study.

PMID- 16445145
TI  - Gastric electrical stimulation: a report of two cases.
AB  - Gastroparesis refractory to prokinetic agents poses a major challenge to the
      physician and patient, alike. In the past 5 years, electrical methods to treat
      gastroparesis have emerged from animal and human experiments to a potentially
      valuable tool in clinical gastroenterology. One of these methods, known as
      gastric electrical stimulation (GES), is being increasingly used in specialized
      centres worldwide, but had never been tried in Ireland. We describe here our
      experience with the first two implantations of gastric neurostimulators performed
      in Ireland and the outcome with these 2 patients. Our results at 6 months show
      reduction in symptoms and improvement in quality of life, which is encouraging
      and should prompt further evaluation of GES for patients with gastroparesis
      refractory to medical therapy.

PMID- 16445146
TI  - Genetic conditions in the Irish Roma gypsy population.
AB  - Roma gypsy represent a new Irish ethnic minority population with a distinct
      cultural and racial heritage. There is a strong Roma tradition of consanguinity,
      which can increase the likelihood of having a child affected by an autosomal
      recessive disorder. We describe 6 patients from the Roma community who had
      presented with 4 different autosomal recessive conditions not previously seen in
      the Irish population, Chronic Granulomatous Disease, HMSN-Russe, and two multiple
      malformation syndromes.

PMID- 16445148
TI  - Etiology of zygomatic fractures.
AB  - We report on the etiology of zygomatic fractures in an Irish population. More
      than half of these injuries are related to interpersonal assault. Treatment of
      these injuries places a considerable burden on the health service.

PMID- 16445147
TI  - The use of hand held mobile phones by drivers.
AB  - The use of mobile phones by drivers has been shown to be associated with an
      increased risk of motor vehicle crashes. The aim of this study was to identify
      the use of hand held mobiles phones by drivers in Ireland. Their use was
      investigated by a direct observation survey of drivers. The study showed that
      3.6% of drivers were using hand held mobile phones while driving. This rate is
      high compared to other studies. Van drivers were three times more likely than
      other drivers to use a mobile phone whilst driving. Legislation needs to be
      introduced to ban their use and thereby reduce the risk of crashes.

PMID- 16445149
TI  - Transient renal failure in twins with maternal Cox-1/Cox-2 use in pregnancy.

PMID- 16445150
TI  - Night eating syndrome and Gotu Kola.

PMID- 16445151
TI  - Accuracy of admitting diagnosis in acute surgical patients by non consultant
      hospital doctors.

PMID- 16445152
TI  - Anti-microbial stewardship for urinary tract infection.

PMID- 16445153
TI  - Antimicrobial resistance in E.coli associated with urinary tract infection in the
      west of Ireland.
AB  - BACKGROUND: Knowledge of antimicrobial resistance patterns in E. coli, the
      predominant pathogen associated with urinary tract infection (UTI) is important
      as a guide in selecting empirical antimicrobial therapy AIMS: To describe the
      antimicrobial susceptibility of E. coli associated with UTI in a region in the
      West of Ireland. METHODS: A collection of 934 E. coli isolates associated with
      UTI were tested for susceptibility to a panel of antimicrobial agents by the disc
      diffusion method of the National Committee for Clinical Laboratory Standards.
      RESULTS: More than 50% of E. coli were resistant to ampicillin, more than 40%
      resistant to sulphonamide and more than 30% resistant to trimethoprim. From 7.9%
      (community) to 12.5% (hospital) are resistant to co-amoxiclav with approximately
      20% of isolates of intermediate susceptibility. In general practice most E. coli
      remain susceptible to nitrofurantoin (96.7%), nalidixic acid (93.9%) and
      ciprofloxacin (94.7%). For all agents rates of resistance were higher in hospital
      as compared with general practice isolates. Three isolates with the phenotype of
      Extended Spectrum Beta-lactamase (ESBL) resistance were detected. CONCLUSIONS:
      Ampicillin/amoxicillin are not suitable for empiric therapy of UTI in general
      practice or hospital patients in this region. There is doubt as to the role of
      trimethorpim or co-trimoxazole for empiric therapy of UTI. Nitrofurantoin,
      nalidixic acid and ciprofloxacin are active against the great majority of UTI
      associated E. coli.

PMID- 16445154
TI  - Changes in outcome following surgery for colorectal cancer: one surgeon's
      experience.
AB  - BACKGROUND: Colorectal cancer (CRC) has the second highest mortality rate of all
      cancers in Ireland. Developments in imaging, surgical technique, and
      perioperative care in the last two decades have altered management. AIMS: To
      determine whether outcome following surgery for CRC in the mid-west has changed
      over a 22-year period. METHODS: Four hundred and twenty-two patients were divided
      into two time periods: Group A (1980-1991, n = 203) and Group B (1992-2002, n =
      219) and demographic, inpatient, and survival data were reviewed. RESULTS: The
      mean age was 67 years, 59% were male. Group B patients had less advanced disease
      at presentation (Dukes' stage D 14% vs 22%, p < 0.05), fewer perioperative
      complications (13% vs 23%, p < 0.05), and fewer local recurrences (6.8% vs 11.8%,
      p < 0.05) than Group A. No difference in 30-day mortality rate or survival was
      detected. CONCLUSIONS: Although perioperative CRC management has improved,
      methods of earlier diagnosis and improvements in adjuvant therapy should be
      explored to improve survival.

PMID- 16445155
TI  - Factors associated with self-reported depression and self-esteem among school
      going adolescents from a geographically defined region in Ireland.
AB  - BACKGROUND: Recent reviews indicate that mental health problems in the young are
      increasing. AIMS: To measure the prevalence of, and risk factors associated with,
      depression and low self-esteem among Irish post-primary students. METHOD: 1,428
      students, randomly selected from a sample of post-primary schools, were given an
      anonymised questionnaire. Analyses included bivariate and multivariate logistic
      regression. RESULTS: Questionnaires were completed by 992 (69.9%) respondents.
      206 (20.8%) had a high depression score. Being from a single parent family (OR
      2.8, 95% CI 1.5-5.4, p<0.001); having low self esteem (OR 13.44 95% CI 8.9-20.3,
      p<0.001); being female (OR, 3.7, 95% CI 2.5-5.6 p<0.001) and having a low fitness
      level (OR 1.8, 95% CI 1.2-2.8 p<0.006) were independently associated with a high
      depression score. CONCLUSIONS: The level of self-reported depression was high
      among these respondents and risk factors identified include having low self
      esteem, being female, being from a single parent family and having a low fitness
      level.

PMID- 16445156
TI  - Non-orthopaedic paediatric trauma in a regional hospital.
AB  - BACKGROUND: In the Republic of Ireland there are no paediatric surgeons outside
      Dublin. Most paediatric trauma is managed in general hospitals by general or
      orthopaedic surgeons. AIM: In this study we audited our experience with
      paediatric trauma in a regional setting. METHODS: We carried out a retrospective
      review of all non-orthopaedic paediatric trauma patients admitted to our
      institution over a two-year period.The method of injury, management and outcome
      were recorded and the TRISS (revised trauma injury severity score) method was
      used to calculate the probability of survival. RESULTS: One hundred and fifty
      four paediatric patients were admitted following trauma. Falls, RTAs and burns
      were the commonest reasons for admission. Twenty nine of these patients (19%)
      required surgical procedures. There were no unexpected deaths. CONCLUSION: The
      majority of paediatric trauma admissions were for minor injuries. A number of
      seriously injured children were successfully treated with no unexpected deaths.

PMID- 16445157
TI  - Increasing rates and changing patterns of hospital admissions for patients with
      inflammatory bowel disease in Ireland: 1996-2001.
AB  - BACKGROUND: The inflammatory bowel diseases require frequent hospital visits. The
      literature suggests that the incidence of IBD may be increasing. AIM: To
      investigate the pattern of admissions of patients with inflammatory bowel disease
      (IBD) to hospital over a five-year period (between 1996 and 2001). METHODS: We
      obtained national data regarding admission rates for patients with IBD from the
      Economic and Social Research Institute (ESRI) during the years 1996 and 2001.
      Local data were gathered from the Hospital In-Patient Enquiry (HIPE) scheme for
      the same years. RESULTS: Over this five-year period, there has been a substantial
      increase in the rate of admission with IBD (58% for Crohn's disease and 25% for
      ulcerative colitis), in particular in the number of day-case admissions for
      patients with Crohn's disease (125%). There has been little change in the number
      of patients undergoing surgery for their disease (Crohn's disease; 24% vs 20% and
      Ulcerative colitis; 17% vs 16.6%) and in the length of hospital stay. CONCLUSION:
      Despite an increase in the rate of admission with IBD, there has been little
      change in the rates of surgical intervention and length of stay. The most
      dramatic increase was seen in the day-case admissions for patients with Crohn's
      disease and may reflect the use of anti-TNFalpha (infliximab) in the treatment of
      this disease.

PMID- 16445158
TI  - Cardiac rehabilitation services in Ireland: the impact of a coordinated national
      development strategy.
AB  - BACKGROUND: The national Cardiovascular Health Strategy including specific plans
      for cardiac rehabilitation was launched in Ireland in 1999. A survey of cardiac
      rehabilitation services was conducted in 2003 to evaluate progress on service
      provision. AIM: To establish levels of service provision, service formats and
      geographic distribution of cardiac rehabilitation services in 2003 and compare
      them with the status pre-Strategy (1998). METHOD: All hospitals in Ireland (n =
      39) admitting cardiac patients to a coronary or intensive care unit were surveyed
      by postal questionnaire. RESULTS: All hospitals provided information and all
      reported providing Phase I cardiac rehabilitation. Seventy-seven per cent (30 of
      39) provided Phase III rehabilitation in 2003 (i.e. outpatient cardiac
      rehabilitation services) compared with 29% (12 of 41) in 1998. Of those hospitals
      currently without programmes, 78% (seven of nine) had plans in place for
      programme establishment. All programmes had trained cardiac rehabilitation
      coordinators, multidisciplinary teams and multiple components as recommended in
      the Strategy. In 82% of hospitals, intervention was provided at Phase II
      (immediate post-discharge period) while 26% of hospitals provided intervention at
      Phase IV (long-term maintenance period). CONCLUSIONS: There have been substantial
      achievements towards the Cardiovascular Health Strategy target of providing
      cardiac rehabilitation services for all relevant hospitals in Ireland over the
      past five years. Service provision of cardiac rehabilitation can benefit from
      collective efforts made across centres to encourage the prioritisation of cardiac
      rehabilitation in national health policy initiatives.

PMID- 16445159
TI  - Laparoscopic adrenalectomy, an initial experience of fifteen cases.
AB  - BACKGROUND: Laparoscopic adrenalectomy is an attractive alternative to open
      surgery, but making the transition can be difficult. AIM: To evaluate the initial
      experience of a general surgical team at a single institution at making the
      transition. METHODS: The details of 15 patients undergoing laparoscopic
      adrenalectomy were prospectively recorded over a 21-month period. RESULTS:
      Fifteen glands were removed from fifteen patients. Nine of these were left-sided.
      The mean gland size was 3.4 cm. Pathology included six non-functioning adenomas,
      four Conn's syndrome, two Cushing's syndrome and three phaeochromocytomas. Mean
      operating time was 74 minutes (range 31-172 minutes), with one conversion to open
      procedure. There were no morbidities and no mortality. CONCLUSION: Our initial
      experience demonstrates this approach to be the ideal technique for removal of
      benign adrenal tumours with significant advantages for the patient.

PMID- 16445160
TI  - Intracapsular fractures of the femoral neck in younger patients.
AB  - BACKGROUND: Most femoral neck fractures in younger patients have a different
      mechanism, treatment, and prognosis from those in elderly patients. AIMS: To
      evaluate the results of internal fixation of femoral neck fractures in patients
      aged between 20 and 60 years, and to determine reasons for failure. PATIENTS AND
      METHODS: Thirty three patients aged between 20 and 60 years who sustained a
      femoral neck fracture between 1995 and 2000 were reviewed. This represents 5.6%
      of the total femoral neck fractures admitted to the unit during this period.
      RESULTS: In 26 patients (78.8%) the fracture resulted from higher energy trauma.
      Of 23 patients with displaced fractures four patients (17.4%) developed avascular
      necrosis and one patient (4.3%) developed non-union. Factors influencing outcome
      were mechanism of injury, pre-operative fracture displacement, adequacy of
      fracture reduction and delay in surgery. CONCLUSION: Our study emphasises the
      importance of timely surgery and adequate reduction of displaced femoral neck
      fractures in younger patients.

PMID- 16445162
TI  - Recent alcohol intake and suicidality--a neuropsychological perspective.
AB  - BACKGROUND: Alcohol use disorders and suicidal behaviours are among the most
      prevalent and damaging of all psychiatric phenomena in Ireland and worldwide.
      Furthermore, alcohol use both chronic and acute has long been identified as a
      potent riskfactor for suicidal behaviour. AIMS: In this paper, the authors review
      the observational and experimental evidence for the acute neuropsychological
      effects of alcohol intake on suicidal ideation and behaviour. METHODS: A
      selective review of the literature was conducted, using the PubMed database.
      Search terms employed included 'alcohol', 'suicide', 'binge' and 'acute alcohol
      intake'. RESULTS: Cognitive mechanisms implicated include alcohol-induced
      deficits in attention-allocation, prospective cognition, autobiographical memory
      and disinhibition. Emotional mechanisms include alcohol-induced dysphoria,
      depression and aggression. CONCLUSIONS: This paper serves to highlight the
      importance of identifying and tackling acute alcohol intake and binge drinking as
      a risk factor for suicidal behaviour.

PMID- 16445161
TI  - Olfactory function in people with genetic risk of dementia.
AB  - BACKGROUND: Screening for sensorial impairment is a secondary objective in the
      context of neurodegenerative diseases, including dementias. For example,
      olfactory dysfunction is among the first signs of Alzheimer's disease. There has
      been no study of olfactory function in Irish subjects at risk of dementia. AIM:
      To investigate olfactory function in non-demented Irish persons, who carry
      genetic risk factors for dementia. METHODS: Thirty-eight Irish adult subjects,
      who are at risk of dementia, were recruited. Cognitive performance and olfactory
      function were assessed and apolipoprotein E (APOE) genotype determined. RESULTS:
      Three and six subjects had a Mini Mental State Examination (MMSE) and Brief Smell
      Identification Test (B-SIT) score, respectively, outside the normal range. While
      five out of the fifteen epsilon-4 allele positive subjects had B-SIT scores
      outside the normal range, only one out of the twenty-three epsilon-4 allele
      negative subjects had; the difference in this frequency was significant
      (P=0.025). There was no significant difference (P=0.266) in the frequency of
      abnormal MMSE scores between epsilon-4 allele groups. CONCLUSION: Further
      investigation is required to explore the reasons for the higher prevalence of
      olfactory dysfunction in epsilon-4 allele positive subjects.

PMID- 16445164
TI  - A case of Resistance to Thyroid Hormone without mutation in the thyroid hormone
      receptor beta.
AB  - BACKGROUND: Resistance to Thyroid Hormone (RTH) is a condition caused by tissue
      hyposensitivity to the effects of circulating thyroid hormone, and may be
      misdiagnosed as hyperthyroidism. AIMS: We report the first case of RTH in an
      Irish patient highlighting the clinical features and the pathophysiological
      mechanism underlying the characteristic laboratory abnormalities found in the
      condition. METHODS: We describe an isolated case of RTH initially misdiagnosed as
      hyperthyroidism, and detail the investigations which ultimately led to the
      correct diagnosis. Genetic screening of the thyroid hormone receptor beta gene
      was performed. RESULTS: Thyroid function tests including T3 suppression test and
      TRH-stimulation test suggested a diagnosis of RTH. Genetic testing failed to
      demonstrate a mutation in the thyroid hormone receptor. CONCLUSION: RTH is a rare
      inherited condition that may be misdiagnosed as hyperthyroidism. The case we
      describe most likely results from a de novo mutation in an as yet undiscovered
      gene. RTH should be considered in patients with elevated thyroid hormone levels
      and normal TSH so that unnecessary and potentially harmful treatment can be
      avoided.

PMID- 16445163
TI  - Maternal brain death--an Irish perspective.
AB  - BACKGROUND: Brainstem death is a concept used in cases in which life-support
      equipment obscures the conventional cardiopulmonary criteria of death. Brainstem
      death during pregnancy is an occasional and tragic occurrence. AIMS: To
      considerthe ethical, legal and medical issues raised by maternal brainstem death.
      METHODS: Medline and Embase search. RESULTS: The death of the mother mandates
      consideration of whether continuing maternal organ supportive measures in an
      attempt to attain foetal viability is appropriate, or whether it constitutes
      futile care. There is no theoretical limit to the duration of time for which
      maternal somatic function may be sustained. However, successful prolongation of
      maternal somatic function in pregnancies of less than 16 weeks gestation has not
      been reported to date. There is no legal imperative to continue maternal somatic
      support where there is little likelihood of a successful foetal outcome.
      CONCLUSION: The difficult issues raised by maternal brainstem death mandates a
      consensus building approach to decision making in this context.

PMID- 16445165
TI  - Irish Neonatal Mortality statistics 2002.

PMID- 16445166
TI  - Using HIPE data as a research and planning tool.

PMID- 16445169
TI  - Quantitative systems analysis as a strategic planning approach for metropolitan
      water service providers.
AB  - Sydney Water selected life cycle assessment (LCA) to inform a review of its
      overall strategic planning document: WaterPlan 21. This assessment covered the
      entire business and has enabled ecological sustainability to be assessed in terms
      of quantitative indicators. The LCA was performed by firstly examining a base
      case which would eventuate if Sydney Water maintained its current operations with
      only the modifications, augmentations and upgrades planned for implementation
      between now and 2021. We then performed a number of scenario analyses to examine
      the benefits of additional demand management, energy efficiency, energy
      generation, supply augmentation and effluent quality initiatives. The results
      indicated significant improvements are available and that some of these measures
      are more desirable than others. We also examined a scenario for the alternative
      delivery of water and wastewater services in new urban areas. This showed
      quantitatively that, since connecting new fringe suburbs to the existing system
      requires significant expenditure on energy for pumping, major improvements in the
      sustainability of water and wastewater systems can be achieved by using
      localised, water-saving alternatives.

PMID- 16445168
TI  - Integrated urban water cycle management: the UrbanCycle model.
AB  - Integrated urban water cycle management presents a new framework in which
      solutions to the provision of urban water services can be sought. It enables new
      and innovative solutions currently constrained by the existing urban water
      paradigm to be implemented. This paper introduces the UrbanCycle model. The model
      is being developed in response to the growing and changing needs of the water
      management sector and in light of the need for tools to evaluate integrated
      watercycle management approaches. The key concepts underpinning the UrbanCycle
      model are the adoption of continuous simulation, hierarchical network modelling,
      and the careful management of computational complexity. The paper reports on the
      integration of modelling capabilities across the allotment, and subdivision
      scales, enabling the interactions between these scales to be explored. A case
      study illustrates the impacts of various mitigation measures possible under an
      integrated water management framework. The temporal distribution of runoff into
      ephemeral streams from a residential allotment in Western Sydney is evaluated and
      linked to the geomorphic and ecological regimes in receiving waters.

PMID- 16445170
TI  - Applications of Artificial Neural Networks in integrated water management:
      fiction or future?
AB  - An Artificial Neural Network (ANN) is nowadays recognized as a very promising
      tool for relating input data to output data. It is said that the possibilities of
      artificial neural networks are unlimited. Here we focus on the potential role of
      neural networks in integrated water management. An Artificial Neural Network
      (ANN) is a mathematical methodology which describes relations between cause
      (input data) and effects (output data) irrespective of the process laying behind
      and without the need for making assumptions considering the nature of the
      relations. The applications are widespread and vary from optimization of
      measuring networks, operational water management, prediction of drinking water
      consumption, on-line steering of wastewater treatment plants and sewage systems,
      up to more specific applications such as establishing a relationship between the
      observed erosion of groyne field sediments and the characteristics of passing
      vessels on the river Rhine. Especially where processes are complex, neural
      networks can open new possibilities for understanding and modelling these kinds
      of complex processes. Besides explaining the method of ANN this paper shows
      different applications. Three examples have been worked out in more detail. An
      intelligent monitoring system is shown for the on-line prediction of water
      consumption, ANN are successfully used for sludge cost monitoring and optimizing
      wastewater treatment and the usage of ANN is shown in optimizing and monitoring
      water quality measuring networks. An ANN appears to be a multiuse and powerful
      tool for modelling complex processes.

PMID- 16445171
TI  - An integrated approach for solving urban water and wastewater crises in the
      Arabian Gulf States.
AB  - Various environmental and economic aspects of urban water and wastewater crises
      in a number of the Arabian Gulf States are discussed. An integrated approach,
      which considers simultaneously the problems of urban waters (shortage of water
      supply and problems associated with urban drainage) and those in connection with
      wastewater (i.e. environmental impact) is proposed. The feasible link between the
      main factors affecting these problems and the anticipated results encourage the
      implementation of the proposed approach. The conclusions suggest immediate
      municipal legislation.

PMID- 16445172
TI  - Analysis and evaluation of methodologies to assess technical urban water systems.
AB  - The paper reports on the methodology and findings of a recent project on behalf
      of the Austrian Federal Ministry of Agriculture, Forestry, Environment and Water
      Management. The Ministry is seeking procedures for combining ecological and
      economic criteria to assess which technical urban water alternatives shall
      receive funding. To this end the current decision making process (DMP) for
      implementing urban water alternatives in Austria has been analyzed and compared
      with the situation elsewhere, e.g. in Sweden. The DMP entails specific
      requirements on assessment, whence the most common decision aid methodologies,
      ranging from LCA-based to multi-criteria methods, have been described and
      evaluated from an environmental, economic, legal and practical point of view,
      turning out recommendations to the Ministry. Their main points are: First the DMP
      should be kept as simple as possible in order to make it transparent. Second the
      aggregation of different criteria groups should and can be avoided. Therefore the
      stakeholders should not be allowed to make trade-offs. Finally clear objectives
      need to be stated.

PMID- 16445173
TI  - Analysis of scenarios for wastewater and urban drainage systems in Brazil based
      on an integrated modeling approach.
AB  - Brazil is currently facing widespread problems in the urban environment
      associated with inadequate wastewater and urban drainage systems, particularly
      for low-income communities. These problems are promoted by the rapid and often
      unplanned urbanization process in developing cities and are compounded by a lack
      of funding, absence of planning, ineffective institutional arrangements, and
      inappropriate policies to provide the framework for integrated wastewater and
      stormwater management. Because planning for the provision of wastewater and urban
      drainage systems is a complex task, an integrated-modeling approach is proposed
      to provide a practical methodology for sanitation and urban drainage planning in
      Brazilian cities. In the model development, as well as technical aspects, other
      aspects related to institutional, financial, socio-economic, environmental and
      public health issues were also taken into account.

PMID- 16445174
TI  - Blueprint for a greener city: growth need not cost the earth.
AB  - The current human use of global natural resources exceeds the long-term
      sustainable capacity of the planet. New and more sustainable ways of building
      cities and providing urban water services are needed. The Australian city of
      Sydney is expected to grow by more than 1 million people over the next 30 years.
      Water use from the Hawkesbury-Nepean River system already exceeds system
      capacity. Current proposals to allocate a greater proportion of low flows to meet
      environmental flow needs will limit urban water allocations and require the
      development of more efficient water and sewerage systems for new and existing
      urban development. This paper presents a hypothetical case study of how water
      supply and sewerage services might be provided for an additional 1 million people
      over a 25-year period. It compares traditional service provision with alternative
      scenarios incorporating water conservation measures, rainwater harvesting and
      water reuse. The paper presents both economic and environmental comparisons. The
      economic comparisons include valuations of environmental externalities in the
      form of environmental levies. It shows that the extra capital costs of water
      conservation, alternative water sources and water reuse scenarios are offset by
      operating savings and environmental benefits. Ecological footprints are reduced
      because of lower water diversions, discharges, energy use and CO2 emissions. The
      paper also discusses the implication of alternative infrastructure ownership and
      water pricing arrangements, and the opportunities to create incentives for
      additional investment in water conservation and reuse projects.

PMID- 16445175
TI  - Optimization of Suzhou Creek Rehabilitation Project Stage I.
AB  - Suzhou Creek is a seriously polluted tidal river in Shanghai, China. With the
      development of Shanghai, there is more and more concern over the "blackness and
      stink" phenomenon of Suzhou Creek. Suzhou Creek Rehabilitation Project was
      launched in 1998, and the planning investment of the Project Stage I was 8.65
      billion yuan (about 1.05 billion US dollars). It is important to predict the
      effectiveness of the project and to optimize it. In this study, the USEPA's WASP
      model is employed to establish a water quality model of Suzhou Creek by using
      data from the Third Trial Low Flow Augmentation on Suzhou Creek in 1999 and other
      monitoring results. Based on this, Suzhou Creek Rehabilitation Project Stage I is
      optimized and adjusted, so the actual investment of the Project Stage I is
      reduced to 6.99 billion yuan. By implementing the Project Stage I, the targets of
      Stage I have been met, the "blackness and stink" phenomenon of the mainstream was
      eliminated by the end of 2000, and the ecological system was improved step by
      step.

PMID- 16445176
TI  - Restoration of fish passage: development and results of a master plan established
      for the Ruhr River Basin.
AB  - According to the central aim of the European Water Framework Directive, the
      protection and sustained management of the aquatic ecological system, the
      ecological condition of a specific type of water, will be the primary parameter
      in future. Aiming at good ecological status in surface water bodies, population
      diversity and abundance of fish and macroinvertebrates is decisive. Free passage
      in river systems, to allow the natural migration of fish and all other aquatic
      organisms, is a prerequisite. To achieve this for the Ruhr River Basin a study
      has been commissioned in order to develop a master plan for river continuum
      restoration. Sustainable development aimed at promoting biodiversity in the
      surface water body system is a key objective. This project is complemented by
      investigations of the sediment--which is the nursery of the fish--in the rivers
      to identify river sections or tributaries which obviously provide a suitable
      habitat for the successful reproduction of big Salmonidae. The master plan
      illustrates the inherent problems of projects aimed at the restoration of fish
      passage in water bodies which are strongly affected by anthropogenic
      modifications. The results obtained may as well be transferred to other
      catchments with similar use patterns.

PMID- 16445177
TI  - River contract in Wallonia (Belgium) and its application for water management in
      the Sourou valley (Burkina Faso).
AB  - Inspired by the experience of a river contract in Wallonia (Belgium) since 1990,
      the implementation of a first river contract has been initiated in a West African
      country, Burkina Faso. This application is not limited to a simple transposition
      of the Walloon model. The Burkina context calls for adaptation to the local
      environmental and socio-economical realities with an adequate partnership
      management. The importance of the mobilization around this project of
      institutional partners, as well as local collectivities, agricultural producers
      and water users in general reveals the great expectations of the actors
      concerning this new tool of water participative management. But will the latter
      be equal to the task? A first assessment has been drawn up one year after the
      launch. During the first year of the project, a participative diagnostic was
      implemented but the understanding of basic notions of water management such as
      'river' (not translatable in the local language), 'watershed', 'contract' were
      not obvious. After the identification of functions and uses of water in the
      basin, an environmental survey was started. This approach allows study with the
      river committees of the priority actions to be developed as a first project of
      restoration of the gallery forest alongside the stream to fight against
      desertification. This project of integrated and participative management of water
      at sub-basin level is a concrete example of solidarity and exchange know-how
      between North and South in the context of a sustainable development.

PMID- 16445178
TI  - Participatory planning in river catchments, an innovative toolkit tested in
      Southern Africa and North West England.
AB  - The European Union Water Framework Directive (WFD) offers an unparalleled
      opportunity for improving river basin management. Active participation is
      essential for its delivery. "End-of-pipe" solutions will not deliver the
      improvements needed to achieve its ambitious goals. This research tested
      DesignWays, a toolkit for participatory planning, as a mechanism for maximizing
      the long-term social and environmental benefits of such stakeholder and community
      participation. It examined the emerging role of "planning for sustainability" in
      the context of river catchments. Sustainable management of water requires
      integration, and recognition of interconnections between systems at different
      levels of scale. This is an endeavour in which systems thinking provides useful
      tools. The development of DesignWays was a conscious attempt to embed 'new
      paradigm' living systems metaphors into a practical planning tool. This paper
      begins with a description of DesignWays and its development in Southern Africa.
      An outline of the context of the action research in North-West England is
      followed by a description of the stages of the process, with highlights of the
      outcomes. This research had two major outcomes: a contribution to theory through
      an in-depth exploration of the theoretical basis of participatory, ecologically
      informed design; and a contribution to practice through investigating DesignWays'
      potential to meet key challenges of the WFD. This research points to the
      importance of understanding participatory planning as a societal process, aiming
      to make the process engaging and meaningful. It has pointed to the need to see
      participatory planning and education for sustainability as an integrated process.
      It demonstrated the benefits of an iterative process in which planning at the
      landscape level of scale informs, and is informed by, work at the site level. It
      has shown that an approach consistent with a living systems paradigm can
      contribute to the development of more integrated, ecologically sound plans.

PMID- 16445179
TI  - Dynamic changes in environment condition and microbial community structure in
      trench and flat seabed sediments of Tokyo Bay, Japan.
AB  - Dynamic changes in the chemical environment in the bottom of overlying water and
      microbial community structure in trench and flat seabed sediments were evaluated
      during summer and autumn in Tokyo Bay, Japan, to elucidate the response of
      microbial community changes as a consequence of dredging activity. Quinone
      profile analysis was performed to evaluate the changes in microbial community
      structure in the sediments. Bottom shape and location of each station affected
      the chemical environment of the overlying water. The trench bottom shape had
      longer anoxic conditions than the flat bottom shape. Nitrogen and phosphorus
      concentrations affected the microbial density in the sediment. During anoxic
      conditions, the ubiquinone/menaquinone ratio (UQ/MK) was less than unity and
      increased with rising dissolved oxygen (DO) concentrations. The dominant quinone
      species in the trench and flat seabed sediments were MK with 6 and 7 isoprene
      units (MK-6 and MK-7) and UQ with 8 and 9 isoprene units (UQ-8 and UQ-9). MK-6
      and UQ-8 containing bacteria might have a great influence on the sulfur cycle of
      the aquatic ecosystem. While, MK-7 and UQ-9 containing bacteria correlated with
      the deposition of phototropic bacteria cells onto the seabed sediment. The trench
      bottom shape contained higher concentrations of MK-6, MK-7, UQ-8 and UQ-9,
      especially during summer.

PMID- 16445180
TI  - Effect of different water management strategies on water and contaminant fluxes
      in Doncaster, United Kingdom.
AB  - In Europe, large volumes of public water supply come from urban aquifers and so
      efficient urban water management and decision tools are essential to maintain
      quality of life both in terms of health, personal freedom and environment. In the
      United Kingdom, this issue gained increased importance with the last year's low
      volumes of groundwater replenishment that resulted in increased water shortages
      all over the country. An urban water volume and quality model (UVQ) was applied
      to a suburb of Doncaster (United Kingdom) to assess the current water supply
      system and to compare it with new potential scenarios of water management. The
      initial results show considerable changes in both water and solute fluxes for
      some scenarios and rather limited changes for others. Changing impermeable roads
      and paved areas to permeable areas, for example, would lead to higher
      infiltration rates that may be welcome from a water resources viewpoint but less
      so from a water quality point of view due to high concentrations of heavy metals.
      The biggest impact on water quality and quantity leaving the system through
      sewer, storm water and infiltration system was clearly obtained by re-using grey
      water from kitchen, bathroom and laundry for irrigation and toilet flush. The
      testing of this strategy led to lower volumes and higher concentrations of
      sewerage, a considerable decrease in water consumption and an increase in
      groundwater recharge. The scenarios were tested neither in terms of costs nor
      social acceptance for either water supplier or user.

PMID- 16445181
TI  - Runoff quality and pollution loadings from a tropical urban catchment.
AB  - Runoff quality draining from 17.14 km2 urban catchment in Johor Bahru, Malaysia,
      was analysed. The land-use consists of residential (30.3%), agricultural (27.3%),
      open space (27.9%), industrial (8.1%) and commercial (6.4%) areas. Three storm
      events were sampled in detail. These storms produced stormflow between 0.84 mm
      and 27.82 mm, and peakflow from 2.19 m3/s to 42.36 m3/s. Water quality showed
      marked variation during storms especially for TSS, BOD and COD with maximum
      concentrations of 778 mg/l, 135 mg/l and 358 mg/l, respectively. Concentrations
      of TOC, DOC, NH3-N, Fe and level of colour were also high. In general, the river
      quality is badly polluted and falls in Class V based on the Malaysian Interim
      National Water Quality Standards. Event Mean Concentrations (EMC) for various
      parameters varied considerably between storms. The largest storm produced higher
      EMC for TSS, NO3-N and SS whereas the smaller storms tend to register higher EMC
      for BOD, COD, NH3-N, TOC, Ca, K, Mg, Fe and Zn. Such variations could be
      explained in terms of pollutant availability and the effects of flushing and
      dilution. Based on a three-month average recurrence interval (ARI) of rainfall,
      the estimated event loadings (ton/ha) of TSS, BOD, COD, TOC, NH3-N and NO3-N were
      0.055, 0.016, 0.012, 0.039, 0.010, 0.0007 and 0.0002, respectively. Heavy metals
      present in trace quantities. Storms with 3 months ARI could capture about 70% of
      the total annual loads of major pollutants.

PMID- 16445182
TI  - Effluent standards for developing countries: combining the technology- and water
      quality-based approach.
AB  - It is a challenge for developing countries to realize socio-economical
      development without impairing water resources in an unacceptable way. A possible
      means for controlling water pollution is through defining, applying and enforcing
      effluent standards for wastewater discharges. However, in many developing
      countries the definition of effluent standards is still poor. They are either too
      stringent because they are based on standards from developed countries, or too
      relaxed and therefore they do not guarantee the safe intended uses of water. In
      order to define an approach for setting effluent standards that suits the needs
      and means of developing counties, water quality management practices in the USA,
      the EU, the New Independent States (NIS) and the Philippines were analyzed and
      compared. Four criteria (protection of the environment, technical viability,
      economic feasibility and institutional capacity requirements) were used to assess
      the suitability of these practices for developing countries. It is concluded that
      a combined approach that is based on best available technology not entailing
      excessive costs and environmental quality standards is the best way to define
      effluent standards that restrict water pollution against affordable costs.

PMID- 16445183
TI  - Inactivation of algal blooms in eutrophic water of drinking water supplies with
      the photocatalysis of TiO2 thin film on hollow glass beads.
AB  - Photocatalytic inactivation of algae, Anabaena, Microcystis, and Melosira, was
      carried out with TiO2-coated Pyrex hollow glass beads under the illumination of
      UV light (370 nm wavelength). After being irradiated with UV light in the
      presence of the TiO2-coated Pyrex glass beads, Anabaena and Microcystis, known as
      typical cyanobacteria, lost their photosynthetic activity, and the string of
      Anabaena cells and the colonies of Microcystis cells were completely separated
      into individual spherical ones. In the case of Melosira, which is a typical
      diatom, however, somewhat lower photocatalytic inactivation efficiency was
      obtained, which was believed to be due to the presence of the inorganic siliceous
      wall surrounding the cells of Melosira. The TiO2-coated hollow glass beads could
      successfully be employed for the practical application in a eutrophicated river
      under sunlight. More than 50% of the chlorophyll-a concentration could be reduced
      by the action of TiO2 photocatalysis.

PMID- 16445184
TI  - Assessing the cost of groundwater pollution: the case of diffuse agricultural
      pollution in the Upper Rhine valley aquifer.
AB  - This paper presents an assessment of the costs of diffuse groundwater pollution
      by nitrates and pesticides for the industrial and the drinking water sectors in
      the Upper Rhine valley, France. Pollution costs which occurred between 1988 and
      2002 are described and assessed using the avoidance cost method. Geo-statistical
      methods (kriging) are then used to construct three scenarios of nitrate
      concentration evolution. The economic consequences of each scenario are then
      assessed. The estimates obtained are compared with the results of a contingent
      valuation study carried out in the same study area ten years earlier.

PMID- 16445185
TI  - Nitrogen fluxes on catchment scale: the influence of hydrological aspects.
AB  - In two catchment areas with altogether eight subcatchments characterising
      different site-specific situations the interaction between anthropogenic
      activities (e.g. agriculture, nutrition and waste water management), nitrogen
      emissions and in stream loads as well as concentrations were studied in detail.
      Groundwater is the most important pathway for nitrogen inputs into surface
      waters. Denitrification in the soil/subsurface/groundwater system controls the
      amount of this input to a high extent. Key factors influencing this process are
      organic carbon availability, geology, precipitation and groundwater recharge
      rates as well as residence time in groundwater. The MONERIS emission model is a
      useful tool to quantify these relationships on (sub-)catchment scale. Areas where
      concentrations in groundwater (e.g. nitrate) tend to be higher due to little
      dilution with water and might be problematic in respect to limit values for
      drinking water, are much less relevant in respect to the loads transported to
      river systems and receiving seas, than regions with high precipitation. In cases
      with high water availability mainly high loads transported downstream and finally
      to the receiving sea are a considerable problem. Within a region mainly areas
      close to river systems contribute to nitrogen discharges to the river system
      because of the short residence times of the groundwater from these areas and-
      related to this--a lower influence of denitrification in the groundwater.

PMID- 16445186
TI  - Estimations of municipal point source pollution in the context of river basin
      management.
AB  - Integrated presentation of total emissions on catchment scale is prerequisite for
      many tasks in integrated management of point and diffuse sources of pollution.
      This paper will focus on emissions of nutrients from municipal point sources.
      Based on calculations of discharges of N, P from households into wastewater and
      on the detailed evaluation of data from 76 municipal wastewater treatments
      plants, this paper presents ranges of specific loads of inhabitants and
      population equivalents in the raw wastewater. In addition data of these treatment
      plants have been evaluated in respect of the treatment efficiency for nitrogen
      and phosphorus (average reduction rates) dependent on the design characteristic
      (with or without nitrification, denitrification or enhanced phosphorus removal).
      The results of the investigation show that the specific N and P loads from
      households in Austria lie within the range 1.6-2.0 g P/(inhabitant.d) and 11- 13
      g N/(inhabitant.d). The specific contribution of industries to municipal
      wastewater varies between 0.3 and 2.0 gP/(pe.d) and 0 and 13 g N/(pe.d) with
      average values of 1.3 g P/(pe.d) and 6.5 g N/(population equivalent (pe)/d). As
      average values for municipal wastewater (contributions from household and
      industry) this leads to specific influent loads of 1.5 g P/(pe.d) and 8.8 g
      N/(pe.d). Average treatment efficiencies of treatment plants are for instance 50%
      nitrogen removal in treatment plants with nitrification and 80% in treatment
      plants with nitrification/denitrification. For phosphorus a removal of about 85%
      can be expected where the treatment plant was designed for enhanced phosphorus
      removal. Finally a method for load estimations based on standard values as
      mentioned above was tested for the estimation of emission from municipal point
      sources of selected regions.

PMID- 16445187
TI  - Combined sewer overflow emissions to bathing waters in Portugal. How to reduce in
      densely urbanised areas?
AB  - The current proposal for a revised European Directive concerning the quality of
      bathing water significantly increases the demands for the control of wet-weather
      discharges. A densely urbanised combined catchment was modelled for a 19-year
      long rainfall series in order to assess the current situation and to evaluate the
      benefits of potential solutions. Storage and advanced physical-chemical treatment
      of stormwater in the STP may significantly contribute for the reduction of the
      overflow volumes but reductions of the spill frequency under 2.5 spill days per
      bathing season are hardly obtained. This study reveals the severe strains that
      the local rainfall pattern may place on the control of the frequency of wet
      weather discharges, pointing to serious technical, social and economical
      implications, at the local and at the national level, if the current proposal for
      a revised European Directive on Bathing Water is enforced.

PMID- 16445188
TI  - Monitor-based evaluation of pollutant load from urban stormwater runoff in
      Beijing.
AB  - As a major pollutant source to urban receiving waters, the non-point source
      pollution from urban runoff needs to be well studied and effectively controlled.
      Based on monitoring data from urban runoff pollutant sources, this article
      describes a systematic estimation of total pollutant loads from the urban areas
      of Beijing. A numerical model was developed to quantify main pollutant loads of
      urban runoff in Beijing. A sub-procedure is involved in this method, in which the
      flush process influences both the quantity and quality of stormwater runoff. A
      statistics-based method was applied in computing the annual pollutant load as an
      output of the runoff. The proportions of pollutant from point-source and non
      point sources were compared. This provides a scientific basis for proper
      environmental input assessment of urban stormwater pollution to receiving waters,
      improvement of infrastructure performance, implementation of urban stormwater
      management, and utilization of stormwater.

PMID- 16445189
TI  - Catchment-scale fluorescence water quality determination.
AB  - Chemical water quality determinants and river water fluorescence were determined
      on the River Tyne, northeast England. Statistically significant relationships
      between nitrate (r = 0.87), phosphate (r = 0.80), ammonia (r = 0.70), biochemical
      oxygen demand (BOD) (r = 0.85) and dissolved oxygen (r = -0.65) and tryptophan
      like fluorescence intensity were observed. The strongest correlations are between
      tryptophan-like intensity and nitrate and phosphate, which in the Tyne catchment
      derive predominantly from point and diffuse source sewage inputs. The correlation
      between BOD and the tryptophan-like fluorescence intensity suggests that this
      fluorescence centre is related to the bioavailable or fluorescence intensity and
      ammonia concentration and dissolved oxygen. The weaker correlation with ammonia
      is due to good ammonia treatment within the wastewater treatment plants within
      the catchment, and that with dissolved oxygen due to the natural aeration of the
      river such that this is not a good indicator of water quality. Mean annual
      tryptophan-like fluorescence intensity, measured by both bench and portable
      spectrometers, agrees well with the General Water Quality Assessment as
      determined by the England and Wales environmental regulators, the Environment
      Agency.

PMID- 16445190
TI  - Quantification of sewer exfiltration using the anti-epileptic drug carbamazepine
      as marker species for wastewater.
AB  - The anti-epileptic drug carbamazepine was used as marker species in wastewater to
      identify and quantify sewer exfiltration. In several studies carbamazepine turned
      out to be hardly removed in wastewater treatment and not or just slightly
      attenuated during bank infiltration. Concentrations in wastewater are generally
      1000 times higher than the limit of quantification. In contrast to many other
      marker species a "young" drug as carbamazepine is discharged to the environment
      only by wastewater. The results from this study carried out in Linz, Austria
      indicate an average exfiltration rate, expressed as percentage of the dry weather
      flow that is lost on the city-wide scale, of 1%. This rate is lower than sewage
      losses reported in most other studies which attempted to quantify exfiltration on
      the basis of groundwater pollution. However, it was also possible to identify one
      area with significant higher sewage losses.

PMID- 16445191
TI  - Biomonitoring of polycyclic aromatic hydrocarbons on hepatocellular carcinoma
      cell line.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are not easily degradable and exist as
      persistent contaminants in water environments. In this study we collected surface
      sediments and water samples from five different ports around Seto Inland Sea
      during October 2003 to April 2004. Fifteen PAHs were detected by gas
      chromatography/mass spectrometer (GC-MS). Expression of CYP1A enzymes was
      measured by a biochemical activation of 7-ethoxy resorufin ortho-deethylase
      (EROD). Total water PAHs ranged from 2.5 ng/l to 132 ng/l, while sediment PAHs
      ranged from 296.3 ng/g to 3992.9 ng/g, which indicate low to high level of PAH
      pollution. Selected isomer ratios (fluoranthene/pyrene to phenanthrene/anthracene
      and, total molecular weight of 202/total molecular weight 202-278), and detected
      PAHs suggested that the origin of pollution could mostly be pyrogenic. The
      highest total sediment PAHs were observed at the Uno Port while the lowest were
      at the New Okayama Port. EROD activity implied that PAH extracted from sediment
      samples affected on CYP1A enzymes expression on the human hepatocellular
      carcinoma cell line in a short exposure time (12 hours). Relatively EROD activity
      showed good correlation between PAH concentration and CYP1A expression for
      sediment samples. The highest EROD values were observed for sediment samples at a
      dose of 5 ppm. In contrast water samples were at the low induction level even
      under the highest exposure concentration (50 ppm), except in Mizushima Port.
      Biomonitoring of water environments by EROD activity could be a necessary tool
      for understanding the effects of PAHs on living organisms at the base of cell
      defense.

PMID- 16445192
TI  - Quantification of dioxin in the sieved fraction of river sediment.
AB  - Dioxin pollution of aquatic sediments has been one of the important environmental
      problems in Japan. Grain size distribution and organic constituents may play
      important roles in dioxins contents in sediments, which have not been well
      investigated. This paper aims to quantify dioxins (PCDDs/Fs and co-PCBs) in
      sieved surface sediment fractions obtained from Kizu and Sumiyoshi Rivers in
      Osaka, Japan. The samples were prepared and analyzed following the 'Manual of the
      Survey and Measurement of Dioxins in Sediment' (Environment Agency of Japan,
      2000). The results showed that TEQ concentrations of dioxins increased with
      decreasing grain size in sediment fractions. Sediment fractions with less than 20
      microm grain size showed the highest dioxin contents. Dioxins with five and six
      chlorine atoms dominated other congeners in less than 20 microm fractions. The
      dioxin TEQ concentrations increased with total organic carbon (TOC), total carbon
      (TC), ignition loss (IL), total sulphur and nitrogen contents in the sediment
      fractions. Thus, reporting dioxin contents in sediments without considering grain
      size distribution may be erroneous, and conventional sedimentation and separation
      techniques might not be useful for treating contaminated sediments. This
      information can be useful for effective remediation of dioxin-contaminated
      sediments.

PMID- 16445193
TI  - Development of communication networks and water quality early warning detection
      systems at drinking water utilities in the Ohio River Valley Basin.
AB  - Source water quality is of major concern to all drinking water utilities. The
      accidental introduction of contaminants to their source water is a constant
      threat to utilities withdrawing water from navigable or industrialized rivers.
      The events of 11 September, 2001 in the United States have heightened concern for
      drinking water utility security as their source water and finished water may be
      targets for terrorist acts. Efforts are underway in several parts of the United
      States to strengthen early warning capabilities. This paper will focus on those
      efforts in the Ohio River Valley Basin.

PMID- 16445194
TI  - Challenges in the implementation of the Water Framework Directive: case study of
      the alpine river Drau, Austria.
AB  - The paper explores a methodology for the definition of ecological water quality
      indicators on the basis of a case study on an alpine river in Austria. Further,
      it discusses a particular interpretation of the combined approach introduced in
      the European Union Water Framework Directive that allows violating emission
      regulations if cost-effective.

PMID- 16445195
TI  - Taxing for stormwater drainage systems.
AB  - This article evaluates the possibility of creating a tax for urban drainage in
      order to make the system self-financing. Average costs of implementation and
      maintenance of the services were used to individualize the charges and definition
      of the tax. The conventional drainage system was evaluated along with a source
      control alternative, water detention in tanks on the lot. The magnitude of the
      values being charged varies in function of the impermeable surface and the
      density of the urban area. Preserving creeks in natural conditions and using
      source control approach, are all options with the advantages of lower investment
      and smaller burden for the users.

PMID- 16445196
TI  - Development of a high-efficiency H2 feeder for bioremediation.
AB  - An electrochemical dissolved hydrogen feeder equipped with a multi-cathode system
      and a high-rate recirculation pump was developed in order to examine its
      feasibility for bioremediation. Results showed that the feeding efficiency was
      remarkably higher than that in former studies. The reason for the enhanced
      hydrogen dissolution rate was thought to be due to the large cathode area by
      applying multiple granular activated carbon electrodes resulting in low current
      density. Two mass balance equations were formulated and applied to analyze the
      performance of the apparatus theoretically. The hydrogen dissolution rate
      calculated from the equations was in fairly good agreement with observed results.
      It was suggested that the electrochemical H2 feeder would be a competitive
      alternative as a hydrogen feeding method for bioremediation.

PMID- 16445197
TI  - Reduction of bromate in groundwater with an ex situ suspended growth bioreactor.
AB  - A potential remediation technique for groundwater contaminated by bromate has
      been investigated, utilising biological bromate reduction to bromide by
      augmentation of indigenous microbial populations. This technique, involving
      addition of a carbon source to contaminated groundwater, is being developed as an
      ex-situ methodology analogous to commercial denitrification systems, but may also
      have in-situ applications. Trials have focussed on a laboratory-scale anaerobic
      suspended growth chemostat system, investigating glucose addition to real
      groundwater supplies. Steady states for a range of glucose and bromate
      concentrations demonstrated bromate reduction up to 700 microgl(-1) (50% of 1400
      microgl(-1) influent) with glucose excess (above 52 mgl(-1)), but specific
      reduction rates (up to 2.83 micromol Br.g dry wt(-1) hr(-1) for 1400 microgl(-1)
      bromate influent) were low compared to denitrification (up to 305 micromol N g
      dry wt(-1) hr(-1)). More recent enrichment trials have demonstrated reduction of
      32 mgl(-1) bromate within a 40 hour residence time with specific reduction rates
      of up to 160.48 micromol Br.g dry wt(-1) hr(-1), suggesting the presence of high
      rate bromate reducing bacterial strains.

PMID- 16445198
TI  - Integration and application of the Rainfall Runoff Library.
AB  - The Rainfall Runoff Library (RRL) provides a convenient platform for implementing
      environment modelling components such as rainfall runoff models, calibration
      tools, and objective functions. A rainfall-runoff model widely known and used in
      South Korea, TANK, is added to the RRL, and used along with the models AWBM and
      SIMHYD to reproduce the historical time series of daily and monthly runoff at the
      Soyanggang Dam and Youngcheon Dam catchments located in South Korea. The features
      of the RRL allow for an easy comparison of different models in a standardised and
      common framework. Three optimisation methods (Genetic algorithm, Rosenbrock
      method and Shuffled Complex Evolution algorithm) were applied to calibrate the
      model parameters using three different objective functions. The applicability of
      each model to these catchments is discussed based on the resulting statistics.

PMID- 16445199
TI  - Development of an integrated analysis procedure for three-ways layout field
      surveys data in lakes.
AB  - Lake water quality systems are extremely complex and every lake is characterized
      by many complicated interactions between biological, chemical and physical
      variables. One of the most important tasks of lake mechanism analysis is to
      examine the relations among important water quality variables and to describe
      such complicated relationships quantitatively, simply and practically. Lake Biwa
      was chosen as a target lake, where a periodic water quality investigation was
      conducted every month from 1979 at 50 sampling sites. The objective of this study
      is to establish an application procedure of three-ways layout data and to present
      a vision including its practical result, expecting that this vision may also
      provide a direction for further research. The results showed that (1) cluster
      analysis following the three-ways layout ANOVA method is very effective in
      presenting water quality variation, (2) correlation analysis of water quality
      indices in each effect of parameters and their interaction between two items
      verifies that their relationships in parameters are different due to different
      mechanisms. (3) An integrated analysis procedure was derived, potentially
      describing those data in forms which convey their important characteristics and
      reveal their significant relationship. The same approach of this analysis
      procedure could be possibly applied for other water quality indices in other
      lakes.

PMID- 16445200
TI  - One question: credit or debit? As health savings accounts gain in popularity,
      insurers and the financial services industry want to bank the cash.
AB  - The Blue Cross and Blue Shield Association has a new sideline-banking. By
      chartering its own bank, the Blues is joining other insurers that have moved into
      financial services to adapt to the changes being wrought by health savings
      accounts. And other insurers have been faster to make the move. The Blues "is
      certainly late to the game" of banking, says analyst Katy Henrickson, left.

PMID- 16445201
TI  - No end in sight. Healthcare tab hits record level, share of economy.

PMID- 16445202
TI  - MedPAC puts on the pressure. Panel wants hospitals to shift from capital
      spending.

PMID- 16445203
TI  - Tenet wades through legal mess. $215 million settlement reached; jury
      deliberates.

PMID- 16445204
TI  - Gentiva poised for growth. Healthfield deal puts company in hospice business.

PMID- 16445205
TI  - Safer, but more expensive. Adding more nurses saves lives but costs more money.

PMID- 16445206
TI  - U.S. emergency care gets C-. 80% of states receive poor or near-failing grades.

PMID- 16445207
TI  - Vendors seen as likely winners. Whoever buys Guidant, devicemakers get more
      clout.

PMID- 16445208
TI  - Ky. relaxed CON plans in limbo. Hospitals oppose changes, fearing surge in
      building.

PMID- 16445209
TI  - Heart to heart in Columbia. S.C. town gets a second cardiac hospital.

PMID- 16445210
TI  - Lost in the doughnut hole. The drug benefit's woes will worsen as seniors
      discover shortcomings.

PMID- 16445211
TI  - Driven to distress. Medical groups fret over expected billing challenges as more
      companies steer employees to consumer-driven health plants.

PMID- 16445212
TI  - Less is more. Too many frivolous pop-up alerts discourage docs from e
      prescribing: article.

PMID- 16445213
TI  - Hard(ly) wired. CPOE systems still a rarity at U.S. hospitals.

PMID- 16445214
TI  - Don't call it a fat farm.

PMID- 16445215
TI  - Mind the protection gap.

PMID- 16445216
TI  - Desperate for improvement.

PMID- 16445217
TI  - The state we're in.

PMID- 16445218
TI  - Important business.

PMID- 16445219
TI  - Keeping out the cold.

PMID- 16445220
TI  - Ask the experts. Non-medical prescribing.

PMID- 16445221
TI  - Getting to grips with general hospital care.
AB  - How can general hospitals ensure that, in accordance with Department of Health
      guidance, the needs of older patients are met? This article describes how one
      trust developed its approach to patient-centred care

PMID- 16445223
TI  - Student learning in care homes.
AB  - This article explores the use of nursing homes as practice placements for pre
      registration nursing students. Although initially disappointed that they had not
      been allocated to acute hospital settings, students changed their views as they
      became more familiar with the learning environment

PMID- 16445222
TI  - Safety issues surrounding the use of bedrails.
AB  - A spot-check on a general medical ward suggested that the use of bedrails was
      excessive and triggered an exploration of best practice

PMID- 16445225
TI  - Promoting adequate nutrition: using artificial feeding.
AB  - An earlier article in this series (Holman et al 2005a) identified that in some
      circumstances the decision is made to administer artificial feeding. Here, Cheryl
      Holman, Sally Roberts and Maggie Nicol describe the reasons why artificial
      feeding may be necessary in older people and how it can be administered.

PMID- 16445224
TI  - Suicide among older people.
AB  - Overall, the number of people who kill themselves across all ages is falling but
      suicide rates among older people remain comparatively high. This article
      considers possible risk factors and suggests ways of reducing and containing
      potential harm. It also explores ways of responding when prevention of suicide
      fails.

PMID- 16445226
TI  - Top team at Chelsea.

PMID- 16445227
TI  - Lives richly lived.

PMID- 16445228
TI  - [Malaria in Moscow in 2000-2004].
AB  - Malaria was eradicated on the territory of Moscow in 1960; its imported cases
      mainly from the countries of Asia and Africa and sporadic cases secondary to the
      imported ones were recorded during the following 40 years. Mass migration of the
      population (businessmen, seasonal workers, etc.) from the endemic CIS countries
      in the late 1990s, particularly to the Moscow Region, increased cases of tertian
      malaria, resulting from the transmission of the infection by the mosquitoes
      Anopheles. A total of 793 cases of malaria, including 27 parasitic carriers, were
      recorded from 2000 to 2004. The proportion of Muscovites was 24.1% of the total
      cases of malaria in 2002 and increased up to 50% in 2004. The causative agents of
      tertian malaria (Plasmodium vivax) were detected in 74.8% of the total number of
      cases. The ongoing importation of malaria from Tadjikistan and Azerbaijan, the
      late establishment of final diagnosis, the shortage of antimalarial drugs make
      the malaria situation worse in Moscow, which requires that antiepidemic measures
      should be intensified in the coming 3 years.

PMID- 16445229
TI  - ["New and recurring" helminthiasis as a potential factor of socioepidemic
      complications in Russia].

PMID- 16445230
TI  - [Impact of effect of natural disasters on the circulation of causative agents of
      parasitic diseases].
AB  - The southern region is marked by a high incidence of parasitic diseases and a
      significant contamination of environmental objects with the eggs and cysts of
      their pathogens. Background examinations revealed the greatest soil contamination
      with helminthic eggs in the Temryuksky District of the Krasnodar Territory and in
      the towns of Vladikavkaz and Digora of the Republic of North Ossetia (Alania).
      The least contamination was found in Rostov-on-Don and the towns of the south
      western area of the Krasnodar Territory. The eggs of Toxocara and astamination.
      There is an increase in the proportion of soil positive tests from 26.6 to 50.0,
      with the high (up to 82.0-100.0%) viability of eggs and a rise in the intensive
      index of their content per kg of soil (from 2.7 to 4.7-11.0). Toxocara eggs were
      mainly detected. The established high proportion of seropositive persons (10.7
      18.0%) among the local population is an additional verification of the wide
      circulation of Toxocara eggs in nature. By the helminthic egg contamination
      index, the soils of localities of the south of Russia are qualified as those of
      moderate epidemic hazard. The floods accompanied by the increased
      helminthological contamination of the upper soil layer may lead to a higher human
      risk for contamination with helminthic diseases.

PMID- 16445231
TI  - [The carnivorous fungi hyphomycetes are natural regulators of the size of animal
      parasitic nematodes].
AB  - The carnivorous fungi hyphomycetes are natural enemies of soil nematodes.
      Laboratory tests examining the effect of the effective strain Duddingtonia
      flagrans T-89 on equine strongyle larvae have indicated that their size can be
      reduced 5-48-fold under the action of the fungus. Using helminth-infected mice as
      an example has ascertained that when the animals are fed a biopreparation, the
      chlamydial spores of the carnivorous fungus D. flagrans remain viable and
      continue their development in the excrements. The dead nematodes show cell
      structural impairments in all tissues and organs, which may be associated with
      the action of the substances contained in the cell envelope of the fungus.

PMID- 16445232
TI  - [Analysis of a complex of biochemical parameters of hepatic functions in
      opisthorchiasis].
AB  - A complex of biochemical parameters of hepatic functions was analyzed in 170
      patients with chronic opisthorchiasis and in 90 apparently healthy dwellers from
      a region wherein opisthorchiasis is endemic. The activity of aspartate
      aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline
      phosphatase, alpha-amylase, and choline esterase and the serum concentrations of
      bilirubin, cholesterol, and glucose were studied. A correlation analysis
      indicated that prolonged Opisthorchis invasion rearranged the system of
      interactions of the biochemical parameters of the functions of the liver and
      pancreas. The auxiliary ("local") standards obtained from a study of a group of
      apparently healthy dwellers from an opisthorchiasis-endemic region may be use to
      consider the results of individual examinations of patients with chronic
      opisthorchiasis in order to correct the processes of treatment and
      rehabilitation.

PMID- 16445233
TI  - [The implication of trichomoniasis and giardiasis in the development of
      inflammatory diseases of small pelvic organs].

PMID- 16445234
TI  - [Choosing the threshold level in the detecting of antibodies to the causative
      agents of Ixodes tick-borne borreliosis by lanthanide immonofluorescence assay].
AB  - The paper describes the algorithm of choice of the threshold level of
      fluorescence, which identifies the positive and negative results of lanthanide
      immunofluorescence assay when IgM and IgG antibodies to the causative agents of
      Ixodes tick-borne borreliosis are detected in the sera of patients. The
      diagnostic specificity index of the method in detecting antibodies of both types
      was 95.3% for the chosen value. According to the time of sampling, the diagnostic
      sensitivity indices for IgM and IgG antibodies were 10.4 to 40.9% and 3.3 to
      18.2%, respectively.

PMID- 16445235
TI  - [Ixodes tick-borne borreliosis with erythema nodosum].
AB  - Ixodes tick-borne borrelioses (ITBB) is a group of natural-and-focal
      transmissible infections caused by Borrelia burgdorferi and characterized by
      multiple organ dysfunctions and a chronic progressive course. The pathognomonic
      marker of an acute period of the disease is migratory erythema at the site of
      tick suction. There may be other skin symptoms: rash on the face, urticaria,
      transient pointed and minor eruptions. Diagnosis presents some certain
      difficulties in these cases. The paper gives a description of rare eruptions in
      ITBB.

PMID- 16445236
TI  - [Vectors of Crimean-Congo hemorrhagic fever virus in the Stavropol Territory].

PMID- 16445237
TI  - [Ixodidae ticks in Bishkek].
AB  - The fauna of Ixodidae ticks was studied in Bishkek in 1998-2004. The city is
      situated in the center of the Chuisk valley, at the foot of the Kirghiz ridge, at
      the boundary of a submountain-plain-arid region and a plain-piedmont-semiarid one
      with steppe fragments. The ticks were gathered on a flag from small mammalians
      caught by Gero traps, from birds, domestic and agricultural animals. A total of
      648 animals of 13 species were examined. The bites of ticks were registered in 98
      persons in the city. A total of 1085 ticks of all developmental phases were
      gathered. The faunal complex of Ixodidae ticks was represented by the following
      species: Ixodes persulcatus Sch (domination index (DI) = 0.45), Haemaphysalis
      punctata Can. Et Fanz (DI = 21.93), Haemaphysalis erinacei Paves (DI = 1.0),
      Dermacentor marginatus Sulter (DI = 0.27), Rhipicephaluspumilio Sch. (DI = 0.84),
      Rhipicephalus sanguineus Latr. (DI = 0.56), Rhipicephalus turanicus Pom (DI =
      74.85), Hyalomma anatolicum Koch (DI = 0.87). The regional and climatic
      conditions of Bishkek and the presence of profeeders in the private sector
      (domestic and agricultural animals, synanthropic rodents, and birds) favor the
      existence of the R. turanicus population. The mosaic pattern of a cultural region
      in the center of the city permits small populations of several species of ticks
      to exist.

PMID- 16445238
TI  - [Design of a Russian sample of the antifascioliasis antihelminthic
      triclabendazole and evaluation of its therapeutic efficiency].

PMID- 16445239
TI  - [Toxicity of some benzothiazole and benzoxazole derivatives having an
      anthelminthic action].

PMID- 16445240
TI  - [The world's first experience of mass treatment for helminthiases in children in
      Cambodia].

PMID- 16445241
TI  - [Experience with insecticidal aerosols used to protect children's health centers
      from attacks of bloodsucking two-winged insects in the environs of Tyumen (2003
      2004)].
AB  - Field trials of an aerosolic regulated dispersity generator used to protect the
      areas of children's health centers (CHC) from bloodsucking two-winged insects
      were performed within the framework of the Tumen Administration's program on
      human protection from tick-borne encephalitis in the 2003 season. The
      technological parameters of the generator's operation and the organizational and
      tactical points of aerosolic treatments were worked on during these trials. The
      latter demonstrated the high efficiency of the use of insecticidal aerosols for
      the protection of CHC areas. The elaborated scheme of measures permitted large
      scale aerosolic treatments in an area of more than 12,000 m2, by protecting 15
      CHCs from attacking of bloodsucking insects. The obtained positive results may be
      used by specialists in other regions of Siberia.

PMID- 16445242
TI  - [Reflection of the problem of pediculosis and its prevention in verbal folk art
      (according to the materials available in Russian verbal folk art)].
AB  - The paper analyzes different forms of oral folk art, dealing with the problem of
      lice and pediculosis, which were collected by V.I. Dal and given in his two
      volume collected works "Proverbs of the Russian people".

PMID- 16445243
TI  - [To the detection of the trematode mesocercariae Alaria alata in the blood of
      domestic dogs and cats].
AB  - Blood samples taken from 2128 domestic dogs and 543 cats in Moscow and the Moscow
      Region were studied by the concentration method using distilled water. The
      studies revealed the infestation with the mesocercariae Alaria alata in 1.9% of
      the dogs and in 1.I1% of the cats. A method was first developed for the life-time
      diagnosis of alariasis in definitive and reserve hosts.

PMID- 16445244
TI  - A new detection algorithm (NDA) based on fuzzy cellular neural networks for white
      blood cell detection.
AB  - White blood cell detection is one of the most basic and key steps in the
      automatic recognition system of white blood cells in microscopic blood images.
      Its accuracy and stability greatly affect the operating speed and recognition
      accuracy of the whole system. But there are only a few methods available for cell
      detection or segmentation due to the complexity of the microscopic images. This
      paper focuses on this issue. Based on the detailed analysis of the existing two
      methods--threshold segmentation followed by mathematical morphology (TSMM), and
      the fuzzy logic method--a new detection algorithm (NDA) based on fuzzy cellular
      neural networks is proposed. NDA combines the advantages of TSMM and the fuzzy
      logic method, and overcomes their drawbacks. With NDA, we can detect almost all
      white blood cells, and the contour of each detected cell is nearly complete. Its
      adaptability is strong and the running speed is expected to be comparatively high
      due to the easy hardware implementation of FCN. Experimental results show good
      performance.

PMID- 16445245
TI  - Combining rate-adaptive cardiac pacing algorithms via multiagent negotiation.
AB  - Simulating and controlling physiological phenomena are notoriously complex tasks
      to tackle and require accurate models of the phenomena of interest. Currently,
      most physiological processes are described by a set of partial models capturing
      specific aspects of the phenomena, and usually their composition does not produce
      effective comprehensive models. A current open issue is thus the development of
      techniques able to effectively describe a phenomenon starting from partial
      models. This is particularly relevant for heart rate regulation modeling where a
      large number of heterogeneous partial models exists. In this paper we make the
      original proposal of adopting a multiagent paradigm, called anthropic agency, to
      provide a powerful and flexible tool for combining partial models of heart rate
      regulation for adaptive cardiac pacing applications. The partial models are
      embedded in autonomous computational entities, called agents, that cooperatively
      negotiate in order to smooth their conflicts on the values of the variables
      forming the global model the multiagent system provides. We experimentally
      evaluate our approach and we analyze its properties.

PMID- 16445246
TI  - TMABoost: an integrated system for comprehensive management of tissue microarray
      data.
AB  - In the last decade, high-throughput technologies such as DNA and tissue
      microarrays (TMAs) have become a means of large-scale investigation of gene
      expression, providing a plethora of new biomedical data in a relatively short
      time. Data collection and organization are critical aspects in this process to
      ensure the quality and reliability of future data interpretation. In this work,
      we propose a comprehensive approach to handle TMA data with the aim of supporting
      and promoting biomarker development. We describe a web-based system for the
      complete management of tissue microarray data in the field of pathology. The
      system has been in use since June, 2003. Our approach includes automatic
      localization and identification of tissue microarray samples, and quantitative
      image analysis that allows high-throughput screening of TMAs by ensuring
      nonsubjective measures and novel prognosis associations. In this paper, we
      present the architecture and the components of this system.

PMID- 16445247
TI  - Intelligent inferencing and haptic simulation for Chinese acupuncture learning
      and training.
AB  - This paper presents an intelligent virtual environment for Chinese acupuncture
      learning and training using state-of-the-art virtual reality technology. It is
      the first step toward developing a comprehensive virtual human model for studying
      Chinese medicine. Students can learn and practice acupuncture in the proposed 3-D
      interactive virtual environment that supports a force feedback interface for
      needle insertion. Thus, students not only "see" but also "touch" the virtual
      patient. With high performance computers, highly informative and flexible
      visualization of acupuncture points of various related meridian and collateral
      can be highlighted to guide the students during training. A computer-based expert
      system using our newly proposed intelligent fuzzy petri net is designed and
      implemented to train the students to treat different diseases using acupuncture.
      Such an intelligent virtual reality system can provide an interesting and
      effective learning environment for Chinese acupuncture.

PMID- 16445248
TI  - Visual positioning of previously defined ROIs on microscopic slides.
AB  - In microscopy, regions of interest are usually much smaller than the whole slide
      area. Various microscopy related medical applications, such as telepathology and
      computer aided diagnosis, are liable to benefit greatly from microscope auto
      positioning on previously defined regions of interest. In this paper, we present
      a method for image-based auto positioning on a microscope slide. The method is
      based on localization of a microscopic query image using a previously acquired
      slide map. It uses geometric hashing, a highly efficient technique drawn from the
      object recognition field. The algorithm exhibits high tolerance to possible
      variations in visual appearance due to slide rotations, scaling and illumination
      changes. Experimental results indicate high reliability of the algorithm.

PMID- 16445249
TI  - A meta-analysis of the training effectiveness of virtual reality surgical
      simulators.
AB  - The increasing use of virtual reality (VR) simulators in surgical training makes
      it imperative that definitive studies be performed to assess their training
      effectiveness. Indeed, in this paper we report the meta-analysis of the efficacy
      of virtual reality simulators in: 1) the transference of skills from the
      simulator training environment to the operating room, and 2) their ability to
      discriminate between the experience levels of their users. The task completion
      time and the error score were the two study outcomes collated and analyzed in
      this meta-analysis. Sixteen studies were identified from a computer-based
      literature search (1996-2004). The meta-analysis of the random effects model
      (because of the heterogeneity of the data) revealed that training on virtual
      reality simulators did lessen the time taken to complete a given surgical task as
      well as clearly differentiate between the experienced and the novice trainees.
      Meta-analytic studies such as the one reported here would be very helpful in the
      planning and setting up of surgical training programs and for the establishment
      of reference 'learning curves' for a specific simulator and surgical task. If any
      such programs already exist, they can then indicate the improvements to be made
      in the simulator used, such as providing for more variety in their case scenarios
      based on the state and/or rate of learning of the trainee.

PMID- 16445250
TI  - Computer-aided kidney segmentation on abdominal CT images.
AB  - In this paper, an effective model-based approach for computer-aided kidney
      segmentation of abdominal CT images with anatomic structure consideration is
      presented. This automatic segmentation system is expected to assist physicians in
      both clinical diagnosis and educational training. The proposed method is a coarse
      to fine segmentation approach divided into two stages. First, the candidate
      kidney region is extracted according to the statistical geometric location of
      kidney within the abdomen. This approach is applicable to images of different
      sizes by using the relative distance of the kidney region to the spine. The
      second stage identifies the kidney by a series of image processing operations.
      The main elements of the proposed system are: 1) the location of the spine is
      used as the landmark for coordinate references; 2) elliptic candidate kidney
      region extraction with progressive positioning on the consecutive CT images; 3)
      novel directional model for a more reliable kidney region seed point
      identification; and 4) adaptive region growing controlled by the properties of
      image homogeneity. In addition, in order to provide different views for the
      physicians, we have implemented a visualization tool that will automatically show
      the renal contour through the method of second-order neighborhood edge detection.
      We considered segmentation of kidney regions from CT scans that contain
      pathologies in clinical practice. The results of a series of tests on 358 images
      from 30 patients indicate an average correlation coefficient of up to 88% between
      automatic and manual segmentation.

PMID- 16445251
TI  - The design of an Internet-based system to maintain home monitoring adherence by
      lung transplant recipients.
AB  - Regimen adherence is a key factor in the success of home monitoring of lung
      transplant recipients. Patients generally adhere satisfactorily with home
      spirometry in the short-term, but adherence tends to decline over time.
      Telehealth and Internet technology provide new methods to address this issue. The
      unique contribution of the Adherence Enhancement Internet Program (AEIP) is the
      integration of multiple adherence enhancement strategies operating in a unified
      approach to the adherence problem, while meshing all user groups to facilitate
      interactions. This Internet-based program focused on promoting subject specific
      strategies was developed to maintain the initial high levels of adherence beyond
      the first year post transplant. The program provides more immediate subject
      feedback related to home monitoring data, reminders from the patient's health
      care providers, educational material, and guidance in dealing with subject
      specific barriers to maintaining adherence. It also simplifies communication
      between patients and health care providers, and supports providers in certain
      patient care tasks. A feasibility trial involving 12 lung transplant recipients
      demonstrated that subjects were able to use the AEIP with little training, found
      it acceptable, and were generally enthusiastic regarding it as a tool to maintain
      or enhance adherence.

PMID- 16445252
TI  - Wavelet-based low-delay ECG compression algorithm for continuous ECG
      transmission.
AB  - The delay performance of compression algorithms is particularly important when
      time-critical data transmission is required. In this paper, we propose a wavelet
      based electrocardiogram (ECG) compression algorithm with a low delay property for
      instantaneous, continuous ECG transmission suitable for telecardiology
      applications over a wireless network. The proposed algorithm reduces the frame
      size as much as possible to achieve a low delay, while maintaining reconstructed
      signal quality. To attain both low delay and high quality, it employs waveform
      partitioning, adaptive frame size adjustment, wavelet compression, flexible bit
      allocation, and header compression. The performances of the proposed algorithm in
      terms of reconstructed signal quality, processing delay, and error resilience
      were evaluated using the Massachusetts Institute of Technology University and
      Beth Israel Hospital (MIT-BIH) and Creighton University Ventricular
      Tachyarrhythmia (CU) databases and a code division multiple access-based
      simulation model with mobile channel noise.

PMID- 16445253
TI  - A support vector machines classifier to assess the severity of idiopathic
      scoliosis from surface topography.
AB  - A support vector machines (SVM) classifier was used to assess the severity of
      idiopathic scoliosis (IS) based on surface topographic images of human backs.
      Scoliosis is a condition that involves abnormal lateral curvature and rotation of
      the spine that usually causes noticeable trunk deformities. Based on the
      hypothesis that combining surface topography and clinical data using a SVM would
      produce better assessment results, we conducted a study using a dataset of 111 IS
      patients. Twelve surface and clinical indicators were obtained for each patient.
      The result of testing on the dataset showed that the system achieved 69-85%
      accuracy in testing. It outperformed a linear discriminant function classifier
      and a decision tree classifier on the dataset.

PMID- 16445254
TI  - A model for the measurement of patient activity in a hospital suite.
AB  - At the time of hospitalization, it is essential to evaluate the general health
      status of a patient and to follow up the trends during therapy. Our work is
      focused on a set of tools for the measurement of patient activity. In this paper,
      we propose a few indicators of the patient activities of daily living, such as
      mobility, agitation, repartitions of stays, and displacements. As a result of
      this work, a diagnostic system was developed that could lead to a deeper
      knowledge of human activity rhythms in normal situations.

PMID- 16445255
TI  - Aggregating automatically extracted regulatory pathway relations.
AB  - Automatic tools to extract information from biomedical texts are needed to help
      researchers leverage the vast and increasing body of biomedical literature. While
      several biomedical relation extraction systems have been created and tested,
      little work has been done to meaningfully organize the extracted relations.
      Organizational processes should consolidate multiple references to the same
      objects over various levels of granularity, connect those references to other
      resources, and capture contextual information. We propose a feature decomposition
      approach to relation aggregation to support a five-level aggregation framework.
      Our BioAggregate tagger uses this approach to identify key features in extracted
      relation name strings. We show encouraging feature assignment accuracy and report
      substantial consolidation in a network of extracted relations.

PMID- 16445256
TI  - A support method for the contextual interpretation of biomechanical data.
AB  - In the clinical field, biomechanical data provided by advanced technical devices
      are still underexploited. Data analysis usually consists of extracting attributes
      or computing synthetic values from temporal data and exploiting them by means of
      a monovariable statistical method. This article proposes a method to support
      clinicians, especially those in orthopedics, in the contextual interpretation of
      biomechanical data. We propose to characterize temporal biomechanical data by
      means of fuzzy space-time windows and to induce fuzzy decision trees to map the
      biomechanical and clinical data related to patients. Then, we present a method
      for objectively explaining a given clinical characteristic of a particular
      patient; this method is derived using the fuzzy rule base generated from the
      trees and a satisfiability measure. We have applied our method to real data in
      order to provide an objective explanation of the subjective self-evaluation of
      the functional status of patients with a shoulder prosthesis, and evaluate it by
      means of the stratified tenfold cross validation method. The mean explanation
      rate--which corresponds to the mean proportion of the patients belonging to test
      sets whose functional state is explained by the proposed method--exceeds 80% for
      more than half of the decision trees, and exceeds 70% for 94% of the trees. By
      supporting clinicians during the biomechanical data interpretation process, our
      method helps them take the objective biomechanical measurements in the medical
      practice into account, particularly in orthopedics. It can also make subjective
      evaluations more objective by mapping subjective and objective data.

PMID- 16445257
TI  - Activity classification using realistic data from wearable sensors.
AB  - Automatic classification of everyday activities can be used for promotion of
      health-enhancing physical activities and a healthier lifestyle. In this paper,
      methods used for classification of everyday activities like walking, running, and
      cycling are described. The aim of the study was to find out how to recognize
      activities, which sensors are useful and what kind of signal processing and
      classification is required. A large and realistic data library of sensor data was
      collected. Sixteen test persons took part in the data collection, resulting in
      approximately 31 h of annotated, 35-channel data recorded in an everyday
      environment. The test persons carried a set of wearable sensors while performing
      several activities during the 2-h measurement session. Classification results of
      three classifiers are shown: custom decision tree, automatically generated
      decision tree, and artificial neural network. The classification accuracies using
      leave-one-subject-out cross validation range from 58 to 97% for custom decision
      tree classifier, from 56 to 97% for automatically generated decision tree, and
      from 22 to 96% for artificial neural network. Total classification accuracy is 82
      % for custom decision tree classifier, 86% for automatically generated decision
      tree, and 82% for artificial neural network.

PMID- 16445258
TI  - Hybrid retinal image registration.
AB  - This work studies retinal image registration in the context of the National
      Institutes of Health (NIH) Early Treatment Diabetic Retinopathy Study (ETDRS)
      standard. The ETDRS imaging protocol specifies seven fields of each retina and
      presents three major challenges for the image registration task. First, small
      overlaps between adjacent fields lead to inadequate landmark points for feature
      based methods. Second, the non-uniform contrast/intensity distributions due to
      imperfect data acquisition will deteriorate the performance of area-based
      techniques. Third, high-resolution images contain large homogeneous
      nonvascular/texureless regions that weaken the capabilities of both feature-based
      and area-based techniques. In this work, we propose a hybrid retinal image
      registration approach for ETDRS images that effectively combines both area-based
      and feature-based methods. Four major steps are involved. First, the vascular
      tree is extracted by using an efficient local entropy-based thresholding
      technique. Next, zeroth-order translation is estimated by maximizing mutual
      information based on the binary image pair (area-based). Then image quality
      assessment regarding the ETDRS field definition is performed based on the
      translation model. If the image pair is accepted, higher-order transformations
      will be involved. Specifically, we use two types of features, landmark points and
      sampling points, for affine/quadratic model estimation. Three empirical
      conditions are derived experimentally to control the algorithm progress, so that
      we can achieve the lowest registration error and the highest success rate.
      Simulation results on 504 pairs of ETDRS images show the effectiveness and
      robustness of the proposed algorithm.

PMID- 16445259
TI  - Artificial intelligence techniques for monitoring dangerous infections.
AB  - The monitoring and detection of nosocomial infections is a very important problem
      arising in hospitals. A hospital-acquired or nosocomial infection is a disease
      that develops after admission into the hospital and it is the consequence of a
      treatment, not necessarily a surgical one, performed by the medical staff.
      Nosocomial infections are dangerous because they are caused by bacteria which
      have dangerous (critical) resistance to antibiotics. This problem is very serious
      all over the world. In Italy, almost 5-8% of the patients admitted into hospitals
      develop this kind of infection. In order to reduce this figure, policies for
      controlling infections should be adopted by medical practitioners. In order to
      support them in this complex task, we have developed a system, called MERCURIO,
      capable of managing different aspects of the problem. The objectives of this
      system are the validation of microbiological data and the creation of a real time
      epidemiological information system. The system is useful for laboratory
      physicians, because it supports them in the execution of the microbiological
      analyses; for clinicians, because it supports them in the definition of the
      prophylaxis, of the most suitable antibi-otic therapy and in monitoring patients'
      infections; and for epidemiologists, because it allows them to identify outbreaks
      and to study infection dynamics. In order to achieve these objectives, we have
      adopted expert system and data mining techniques. We have also integrated a
      statistical module that monitors the diffusion of nosocomial infections over time
      in the hospital, and that strictly interacts with the knowledge based module.
      Data mining techniques have been used for improving the system knowledge base.
      The knowledge discovery process is not antithetic, but complementary to the one
      based on manual knowledge elicitation. In order to verify the reliability of the
      tasks performed by MERCURIO and the usefulness of the knowledge discovery
      approach, we performed a test based on a dataset of real infection events. In the
      validation task MERCURIO achieved an accuracy of 98.5%, a sensitivity of 98.5%
      and a specificity of 99%. In the therapy suggestion task, MERCURIO achieved very
      high accuracy and specificity as well. The executed test provided many insights
      to experts, too (we discovered some of their mistakes). The knowledge discovery
      approach was very effective in validating part of the MERCURIO knowledge base,
      and also in extending it with new validation rules, confirmed by interviewed
      microbiologists and specific to the hospital laboratory under consideration.

PMID- 16445260
TI  - Implementation of a real-time human movement classifier using a triaxial
      accelerometer for ambulatory monitoring.
AB  - The real-time monitoring of human movement can provide valuable information
      regarding an individual's degree of functional ability and general level of
      activity. This paper presents the implementation of a real-time classification
      system for the types of human movement associated with the data acquired from a
      single, waist-mounted triaxial accelerometer unit. The major advance proposed by
      the system is to perform the vast majority of signal processing onboard the
      wearable unit using embedded intelligence. In this way, the system distinguishes
      between periods of activity and rest, recognizes the postural orientation of the
      wearer, detects events such as walking and falls, and provides an estimation of
      metabolic energy expenditure. A laboratory-based trial involving six subjects was
      undertaken, with results indicating an overall accuracy of 90.8% across a series
      of 12 tasks (283 tests) involving a variety of movements related to normal daily
      activities. Distinction between activity and rest was performed without error;
      recognition of postural orientation was carried out with 94.1% accuracy,
      classification of walking was achieved with less certainty (83.3% accuracy), and
      detection of possible falls was made with 95.6% accuracy. Results demonstrate the
      feasibility of implementing an accelerometry-based, real-time movement classifier
      using embedded intelligence.

PMID- 16445261
TI  - Incorporating the sense of smell into patient and haptic surgical simulators.
AB  - It is widely recognized that the sense of smell plays an important role in the
      field of medicine. The sense of smell not only assists the physician in the
      diagnosis of certain disorders, but it also plays a surgical role as well.
      Historically, learning this skill was mostly contingent upon some level of
      clinical exposure to medically related odors. The advent of computerized scent
      production devices could change this. This article proposes a surgical simulation
      model that incorporates olfactory technologies into existing patient and haptic
      surgical simulators. If incorporated into virtual educational settings such as
      these, computerized scent production devices could be used not only as a novel
      way to enhance the virtual experience, but also as a way for medical students to
      begin to recognize the important role that the sense of smell plays during both
      diagnosis and surgery.

PMID- 16445262
TI  - Tracking of left ventricular long axis from real-time three-dimensional
      echocardiography using optical flow techniques.
AB  - Two-dimensional echocardiography (2DE) is routinely used in clinical practice to
      measure left ventricular (LV) mass, dimensions, and function. The reliability of
      these measurements is highly dependent on the ability to obtain nonforeshortened
      long axis (LA) images of the left ventricle from transthoracic apical acoustic
      windows. Real time three-dimensional echocardiography (RT3DE) is a novel imaging
      technique that allows the acquisition of dynamic pyramidal data structures
      encompassing the entire ventricle and could potentially overcome the effects of
      LA foreshortening. Accordingly, the aim of this paper was to develop a nearly
      automated method based on optical flow techniques for the measurement of the left
      ventricular (LV) LA throughout the cardiac cycle from RT3DE data. The LV LA
      measurements obtained with the automated technique has been compared with LA
      measurements derived from manual selection of the LA from a volumetric display of
      RT3DE data. High correlation (r = .99, SEE = 1.8%, y = .94x + 5.3), no
      significant bias (-0.18 mm), and narrow limits of agreement (SD: 1.91 mm) were
      found. The comparison between the LA length derived from 2DE and RT3DE data
      showed significant underestimation of the 2DE based measurements. In conclusion,
      this study proves that RT3DE data overcome the effects of foreshortening and
      indicates that the method we propose allows fast and accurate quantification of
      LA length throughout the cardiac cycle.

PMID- 16445263
TI  - Quality assessment of ECG compression techniques using a wavelet-based diagnostic
      measure.
AB  - Electrocardiograph (ECG) compression techniques are gaining momentum due to the
      huge database requirements and wide band communication channels needed to
      maintain high quality ECG transmission. Advances in computer software and
      hardware enable the birth of new techniques in ECG compression, aiming at high
      compression rates. In general, most of the introduced ECG compression techniques
      depend on their evaluation performance on either inaccurate measures or measures
      targeting random behavior of error. In this paper, a new wavelet-based quality
      measure is proposed. A new wavelet-based quality measure is proposed. The new
      approach is based on decomposing the segment of interest into frequency bands
      where a weighted score is given to the band depending on its dynamic range and
      its diagnostic significance. A performance evaluation of the measure is conducted
      quantitatively and qualitatively. Comparative results with existing quality
      measures show that the new measure is insensitive to error variation, is
      accurate, and correlates very well with subjective tests.

PMID- 16445265
TI  - Piecewise parametric interpolation for temporal compression of multijoint
      movement trajectories.
AB  - Computer animation of sign language used by deaf individuals has been produced
      from 51 time-varying trajectories of the fingertips, the centers of rotation of
      the joints of the hands and arms, and facial landmarks. These trajectories are
      sampled at 1/5th the National Television Systems Committee (NTSC) video frame
      rate and interpolated using piecewise sequences of cubic Bezier splines. The
      resulting trajectories are used to control sparse, stick figure animations of
      sign language resulting in considerable spatiotemporal compression with
      intelligibility in the range of 90%. This method introduces an additional 5:1
      compression in the temporal domain that has not been previously exploited, and is
      potentially useful in sign language telecommunication, multimedia presentations,
      and gesture recognition.

PMID- 16445264
TI  - Impact of monitoring technology in assisted living: outcome pilot.
AB  - This paper describes a study designed to assess the acceptance and some
      psychosocial impacts of monitoring technology in assisted living. Monitoring
      systems were installed in 22 assisted living units to track the activities of
      daily living (ADLs) and key alert conditions of residents (15 of whom were
      nonmemory care residents). Activity reports and alert notifications were sent to
      professional caregivers who provided care to residents participating in the
      study. Diagnostic use of the monitoring data was assessed. Nonmemory care
      residents were surveyed and assessed using the Satisfaction With Life Scale
      (SWLS) instrument. Pre- and post-installation SWLS scores were compared. Older
      adult participants accepted monitoring. The results suggest that monitoring
      technologies could provide care coordination tools that are accepted by residents
      and may have a positive impact on their quality of life.

PMID- 16445266
TI  - Research training grants awared to help fight AIDS and tuberculosis.

PMID- 16445267
TI  - Executive function testing to diagnose, subtype dementias.

PMID- 16445268
TI  - Who should care for patients with HIV/AIDS?

PMID- 16445269
TI  - Initial evaluation of vertigo.
AB  - Benign paroxysmal positional vertigo, acute vestibular neuronitis, and Meniere's
      disease cause most cases of vertigo; however, family physicians must consider
      other causes including cerebrovascular disease, migraine, psychological disease,
      perilymphatic fistulas, multiple sclerosis, and intracranial neoplasms. Once it
      is determined that a patient has vertigo, the next task is to determine whether
      the patient has a peripheral or central cause of vertigo. Knowing the typical
      clinical presentations of the various causes of vertigo aids in making this
      distinction. The history (i.e., timing and duration of symptoms, provoking
      factors, associated signs and symptoms) and physical examination (especially of
      the head and neck and neurologic systems, as well as special tests such as the
      Dix-Hallpike maneuver) provide important clues to the diagnosis. Associated
      neurologic signs and symptoms, such as nystagmus that does not lessen when the
      patient focuses, point to central (and often more serious) causes of vertigo,
      which require further work-up with selected laboratory and radiologic studies
      such as magnetic resonance imaging.

PMID- 16445270
TI  - Information from your family doctor. Vertigo: what you should know.

PMID- 16445271
TI  - Nutritional assessment and counseling for prevention and treatment of
      cardiovascular disease.
AB  - Physicians face several barriers to counseling their patients about nutrition,
      including conflicting evidence of the benefit of counseling, limited training and
      understanding of the topic, and imperfect and varied guidelines to follow.
      Because cardiovascular disease remains the leading cause of death in
      industrialized nations, family physicians should provide more than pharmacologic
      interventions. They must identify the patient's dietary habits and attitudes and
      provide appropriate counseling. Tools are available to help, and a seven-step
      approach to nutritional therapy for the dyslipidemic patient may be useful. These
      steps include recommending increased intake of plant proteins; increased intake
      of omega-3 fatty acids; modification of the types of oils used in food
      preparation; decreased intake of saturated and trans-fatty acids; increased
      intake of whole grains and dietary fiber (especially soluble fiber) and decreased
      intake of refined grains; modification of alcohol intake, if needed; and regular
      exercise. Recommendations should be accompanied by patient information handouts
      presenting acceptable substitutions for currently identified detrimental food
      choices.

PMID- 16445272
TI  - Information from your family doctor. Keeping your heart healthy through good
      nutrition and exercise.

PMID- 16445273
TI  - Preventive counseling, screening, and therapy for the patient with newly
      diagnosed HIV infection.
AB  - The epidemic of human immunodeficiency virus (HIV) continues, and the infection
      is converting into a treatable chronic disease; therefore, it is increasingly
      important for family physicians to be current with and comfortable in providing
      basic care to patients infected with HIV. Important aspects of counseling and
      patient education include stabilization of psychosocial issues and prevention of
      HIV transmission through behavior change counseling. Reporting HIV and acquired
      immunodeficiency syndrome (AIDS) is mandatory in most states, whereas partner
      notification laws vary from state to state. Baseline evaluation includes
      screening for comorbid conditions such as viral hepatitis, syphilis, and
      tuberculosis, as well as common HIV-related manifestations such as recurrent
      candidal infections and thrombocytopenia. Baseline testing includes CD4+ T
      lymphocyte cell counts and HIV viral RNA levels to assess HIV disease stage, and
      numerous studies to screen for opportunistic infections. Initial preventive
      interventions include patient education to reduce exposure to infections,
      treatment of comorbid conditions such as human papillomavirus-related dysplasia,
      and vaccinations such as for pneumococcus and hepatitis B. Prophylaxis against
      opportunistic pathogens is recommended when CD4+ cell counts fall below 200 cells
      per mm3. Lastly, the indications for antiretroviral therapy include symptomatic
      patients or those with AIDS, and pre-AIDS patients with CD4+ cell counts of 200
      to 350 cells per mm3 or HIV RNA above 55,000 to 100,000 copies per mL.

PMID- 16445275
TI  - Treating adult women with suspected UTI.

PMID- 16445274
TI  - Hyperkalemia.
AB  - Hyperkalemia is a potentially life-threatening metabolic problem caused by
      inability of the kidneys to excrete potassium, impairment of the mechanisms that
      move potassium from the circulation into the cells, or a combination of these
      factors. Acute episodes of hyperkalemia commonly are triggered by the
      introduction of a medication affecting potassium homeostasis; illness or
      dehydration also can be triggers. In patients with diabetic nephropathy,
      hyperkalemia may be caused by the syndrome of hyporeninemic hypoaldosteronism.
      The presence of typical electrocardiographic changes or a rapid rise in serum
      potassium indicates that hyperkalemia is potentially life threatening. Urine
      potassium, creatinine, and osmolarity should be obtained as a first step in
      determining the cause of hyperkalemia, which directs long-term treatment.
      Intravenous calcium is effective in reversing electrocardiographic changes and
      reducing the risk of arrhythmias but does not lower serum potassium. Serum
      potassium levels can be lowered acutely by using intravenous insulin and glucose,
      nebulized beta2 agonists, or both. Sodium polystyrene therapy, sometimes with
      intravenous furosemide and saline, is then initiated to lower total body
      potassium levels.

PMID- 16445276
TI  - An itch that must be scratched.

PMID- 16445277
TI  - Impact of naturally occurring variants of HCV protease on the binding of
      different classes of protease inhibitors.
AB  - HCV drug discovery efforts have largely focused on genotype 1 virus due to its
      prevalence and relatively poor response to current therapy. However, patients
      infected with genotype 2 and 3 viruses account for a significant number of cases
      and would also benefit from new therapies. In vitro studies using two chemically
      distinct protease inhibitors with clinical potential showed that one, VX-950, was
      equally active on proteases from all three genotypes, whereas the other, BILN
      2061, was significantly less active on genotype 2 and 3 proteases. Naturally
      occurring variation near the inhibitor binding site was identified based on
      sequence alignment of the protease region from genotype 1-3 sequences.
      Substitution of amino acids in genotype 1 based on genotype 2 and 3 has revealed
      residues which impact binding of BILN 2061. Substitution of residues 78-80,
      together with 122 and 132, accounted for most of the reduced sensitivity of
      genotype 2. The most critical position affecting inhibitor binding to genotype 3
      protease was 168. Substitution of residues at positions 168, 123, and 132 fully
      accounted for the reduced sensitivity of genotype 3. Comparative studies of BILN
      2061 and a closely related nonmacrocycle inhibitor suggested that the rigidity of
      BILN 2061, while conferring greater potency against genotype 1, rendered it more
      sensitive to variations near the binding site. Free energy perturbation analysis
      confirmed the experimental observations. The identification of naturally
      occurring variations which can affect inhibitor binding is an important step in
      the design of broad-spectrum, second generation protease inhibitors.

PMID- 16445278
TI  - Presence of a putative vesicular inositol 1,4,5-trisphosphate-sensitive
      nucleoplasmic Ca2+ store.
AB  - The inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are widely localized in both
      the heterochromatin and euchromatin regions. We found recently the presence of
      nucleoplasmic complexes that are composed of phospholipids, IP(3)R/Ca(2+)
      channels, and Ca(2+) storage protein chromogranin B (CGB). Close examination and
      3D image reconstruction of these complexes revealed numerous vesicular structures
      with an average diameter of approximately 50 nm that are primarily interspersed
      between the heterochromatins. IP(3) rapidly released Ca(2+) from these
      structures, but other inositol phosphates, inositol 1,4-bisphosphate, inositol
      1,3,4-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate, failed to release
      Ca(2+). Addition of heparin or IP(3)R antibody blocked the IP(3)-induced Ca(2+)
      releases, indicating the release of Ca(2+) through the IP(3)R/Ca(2+) channels.
      Given the presence of the IP(3)R/Ca(2+) channels and Ca(2+) storage protein CGB
      in these vesicular structures, we postulate that these vesicles are the IP(3)
      sensitive nucleoplasmic Ca(2+) stores. Abundance of the vesicular Ca(2+) stores
      between the heterochromatins appeared to imply critical roles these vesicular
      Ca(2+) stores play in controlling the Ca(2+) concentrations of the chromosomes.

PMID- 16445279
TI  - Dependence of diffusional mobility of integral inner nuclear membrane proteins on
      A-type lamins.
AB  - Integral proteins of the nuclear envelope inner membrane have been proposed to
      reach their sites by diffusion after their co-translational insertion in the
      rough endoplasmic reticulum. They are then retained in the inner nuclear membrane
      by binding to nuclear structures. One such structure is the nuclear lamina, an
      intermediate filament meshwork composed of A-type and B-type lamin proteins.
      Emerin, MAN1, and LBR are three integral inner nuclear membrane proteins. We
      expressed these proteins fused to green fluorescent protein in embryonic
      fibroblasts from wild-type mice and Lmna -/- mice, which lack A-type lamins. We
      then studied the diffusional mobilities of emerin, MAN1, and LBR using
      fluorescence recovery after photobleaching. We show that emerin and MAN1, but not
      LBR, are more mobile in the inner nuclear membrane of cells from Lmna -/- mice
      than in cells from wild-type mice. In cells from Lmna -/- mice expressing
      exogenous lamin A, the protein mobilities were similar to those in cells from
      wild-type mice. This supports a model where emerin and MAN1 are at least partly
      retained in the inner nuclear membrane by binding to A-type lamins, while LBR
      depends on other binding partners for its retention.

PMID- 16445280
TI  - Effects of a distal mutation on active site chemistry.
AB  - Previous studies of Escherichia coli dihydrofolate reductase (ecDHFR) have
      demonstrated that residue G121, which is 19 A from the catalytic center, is
      involved in catalysis, and long distance dynamical motions were implied.
      Specifically, the ecDHFR mutant G121V has been extensively studied by various
      experimental and theoretical tools, and the mutation's effect on kinetic,
      structural, and dynamical features of the enzyme has been explored. This work
      examined the effect of this mutation on the physical nature of the catalyzed
      hydride transfer step by means of intrinsic kinetic isotope effects (KIEs), their
      temperature dependence, and activation parameters as described previously for
      wild type ecDHFR [Sikorski, R. S., et al. (2004) J. Am. Chem. Soc. 126, 4778
      4779]. The temperature dependence of initial velocities was used to estimate
      activation parameters. Isotope effects on the preexponential Arrhenius factors,
      and the activation energy, could be rationalized by an environmentally coupled
      hydrogen tunneling model, similar to the one used for the wild-type enzyme. Yet,
      in contrast to that in the wild type, fluctuations of the donor-acceptor distance
      were now required. Secondary (2 degrees ) KIEs were also measured for both H- and
      D-transfer, and as in the case of the wild-type enzyme, no coupled motion was
      detected. Despite these similarities, the reduced rates, the slightly inflated
      primary (1 degrees ) KIEs, and their temperature dependence, together with
      relatively deflated 2 degrees KIEs, indicate that the potential surface
      prearrangement was not as ideal as for the wild-type enzyme. These findings
      support theoretical studies suggesting that the G121V mutation led to a different
      conformational ensemble of reactive states and less effective rearrangement of
      the potential surface but has an only weak effect on H-tunneling.

PMID- 16445282
TI  - Sequence dependence of the stability of RNA hairpin molecules with six nucleotide
      loops.
AB  - Thermodynamic parameters are reported for hairpin formation in 1 M NaCl by RNA
      sequence of the types GCGXUAAUYCGC and GGUXUAAUYACC with Watson-Crick loop
      closure, where XY is the set of 10 possible mismatch base pairs. A nearest
      neighbor analysis of the data indicates the free energy of loop formation at 37
      degrees C varies from 3.1 to 5.1 kcal/mol. These results agree with the model
      previously developed [Vecenie, C. J., and Serra, M. J. (2004) Biochemistry 43,
      11813] to predict the stability of RNA hairpin loops: DeltaG degrees (37L(n) =
      DeltaG degrees (37i(n) + DeltaG degrees (37MM) - 0.8 (if first mismatch is GA or
      UU) - 0.8 (if first mismatch is GG and loop is closed on the 5' side by a
      purine). Here, DeltaG degrees (37i(n) is the free energy for initiating a loop of
      n nucleotides, and DeltaG degrees (37MM) is the free energy for the interaction
      of the first mismatch with the closing base pair. Thermodynamic parameters are
      also reported for hairpin formation in 1 M NaCl by RNA sequence of the types
      GACGXUAAUYUGUC and GGUXUAAUYGCC with GU base pair closure, where XY is the set of
      10 possible mismatch base pairs. A nearest-neighbor analysis of the data
      indicates the free energy of loop formation at 37 degrees C varies from 3.6 to
      5.3 kcal/mol. These results allow the development of a model for predicting the
      stability of hairpin loops closed by GU base pairs. DeltaG degrees (37L(n)
      (kcal/mol) = DeltaG degrees (37i(n) - 0.8 (if the first mismatch is GA) - 0.8 (if
      the first mismatch is GG and the loop is closed on the 5' side by a purine). Note
      that for these hairpins, the stability of the loops does not depend on DeltaG
      degrees (37MM). For hairpin loops closed by GU base pairs, the DeltaG degrees
      (37i(n) values, when n = 4, 5, 6, 7, and 8, are 4.9, 5.0, 4.6, 5.0, and 4.8
      kcal/mol, respectively. The model gives good agreement when tested against six
      naturally occurring hairpin sequences. Thermodynamic values for terminal
      mismatches adjacent to GC, GU, and UG base pairs are also reported.

PMID- 16445281
TI  - Exploring the recognition of quadruplex DNA by an engineered Cys2-His2 zinc
      finger protein.
AB  - We have recently described an engineered zinc finger protein (Gq1) that binds
      with high specificity to the intramolecular G-quadruplex formed by the human
      telomeric sequence 5'-(GGTTAG)(5)-3', and that inhibits the activity of the
      enzyme telomerase in vitro. Here we report site-directed mutagenesis,
      biophysical, and molecular modeling studies that provide new insights into
      quadruplex recognition by the zinc finger scaffold. We show that any one finger
      of Gq1 can be replaced with the corresponding finger of Zif268, without
      significant loss of quadruplex affinity or quadruplex versus duplex
      discrimination. Replacement of two fingers, with one being finger 2, of Gq1 by
      Zif268 results in significant impairment of quadruplex recognition and loss of
      discrimination. Molecular modeling suggests that the zinc fingers of Gq1 can bind
      to the human parallel-stranded quadruplex structure in a stable arrangement,
      whereas Zif268-quadruplex models show significantly weaker binding energy.
      Modeling also suggests that an important role of the key protein finger residues
      in the Gq1-quadruplex complex is to maintain Gq1 in an optimum conformation for
      quadruplex recognition.

PMID- 16445283
TI  - Comparison of penetratin and other homeodomain-derived cell-penetrating peptides:
      interaction in a membrane-mimicking environment and cellular uptake efficiency.
AB  - Antennapedia and other homeoproteins have the unique ability to efficiently
      translocate across biological membranes, a property that is mediated by the third
      helix of the homeodomain. To analyze the effects of sequence divergence in the
      homeodomain, we have compared the cellular uptake efficiencies and interaction
      properties in a membrane-mimicking environment of four peptides corresponding to
      the third helix sequence of Antennapedia, Engrailed-2, HoxA-13, and Knotted-1.
      NMR studies revealed that these peptides adopt helical conformations in SDS
      micelles. Their localization with respect to the micelle was investigated using
      Mn(2+) as a paramagnetic probe. Peptides are positioned parallel to the micelle
      surface, but subtle differences in the depth of immersion were observed. Using a
      recently developed method for quantification of CPP cellular uptake based on
      MALDI-TOF mass spectrometry, all of these peptides were found to translocate into
      cells but with large differences in their uptake efficiencies. The peptide with
      the highest uptake efficiency was found to be the least deeply inserted within
      the micelle, indicating that electrostatic surface interactions may be a major
      determinant for membrane translocation. A new cell-penetrating peptide derived
      from Knotted-1 homeodomain with improved uptake properties compared to penetratin
      is introduced here.

PMID- 16445284
TI  - Global effects of the energetics of coenzyme binding: NADPH controls the protein
      interaction properties of human cytochrome P450 reductase.
AB  - The thermodynamics of coenzyme binding to human cytochrome P450 reductase (CPR)
      and its isolated FAD-binding domain have been studied by isothermal titration
      calorimetry. Binding of 2',5'-ADP, NADP(+), and H(4)NADP, an isosteric NADPH
      analogue, is described in terms of the dissociation binding constant (K(d)), the
      enthalpy (DeltaH(B)) and entropy (TDeltaS(B)) of binding, and the heat capacity
      change (DeltaC(p)). This systematic approach allowed the effect of coenzyme redox
      state on binding to CPR to be determined. The recognition and stability of the
      coenzyme-CPR complex are largely determined by interaction with the adenosine
      moiety (K(d2)(')(,5)(')(-ADP) = 76 nM), regardless of the redox state of the
      nicotinamide moiety. Similar heat capacity change (DeltaC(p)) values for 2',5'
      ADP (-210 cal mol(-)(1) K(-)(1)), NADP(+) (-230 cal mol(-)(1) K(-)(1)), and
      H(4)NADP (-220 cal mol(-)(1) K(-)(1)) indicate no significant contribution from
      the nicotinamide moiety to the binding interaction surface. The coenzyme binding
      stoichiometry to CPR is 1:1. This result validates a recently proposed one-site
      kinetic model [Daff, S. (2004) Biochemistry 43, 3929-3932] as opposed to a two
      site model previously suggested by us [Gutierrez, A., Lian, L.-Y., Wolf, C. R.,
      Scrutton, N. S., and Roberts, C. G. K. (2001) Biochemistry 40, 1964-1975].
      Calorimetric studies in which binding of 2',5'-ADP to CPR (TDeltaS(B) = -13400 +/
      200 cal mol(-)(1), 35 degrees C) was compared with binding of the same ligand to
      the isolated FAD-binding domain (TDeltaS(B) = -11200 +/- 300 cal mol(-)(1), 35
      degrees C) indicate that the number of accessible conformational substates of the
      protein increases upon 2',5'-ADP binding in the presence of the FMN-binding
      domain. This pattern was consistently observed along the temperature range that
      was studied (5-35 degrees C). This contribution of coenzyme binding energy to
      domain dynamics in CPR agrees with conclusions from previous temperature-jump
      studies [Gutierrez, A., Paine, M., Wolf, C. R., Scrutton, N. S., and Roberts, G.
      C. K. (2002) Biochemistry 41, 4626-4637]. A combination of calorimetry and
      stopped-flow spectrophotometry kinetics experiments showed that this linkage
      between coenzyme binding energetics and diffusional domain motion impinges
      directly on the molecular recognition of cytochrome c by CPR. Single-turnover
      reduction of cytochrome c by CPR (k(max) = 15 s(-)(1), K(d) = 37 microM) is
      critically coupled to coenzyme binding through ligand-induced motions that enable
      the FMN-binding domain to overcome a kinetically unproductive conformation. This
      is remarkable since the FMN-binding domain is not directly involved in coenzyme
      binding, the NADP(H) binding site being fully contained in the FAD-binding
      domain. Sequential rapid mixing measurements indicate that harnessing of coenzyme
      binding energy to the formation of a kinetically productive CPR-cytochrome c
      complex is a highly synchronized event. The inferred half-time for the decay of
      this productive conformation (tau(50)) is 330 +/- 70 ms only. Previously proposed
      structural and kinetic models are discussed in light of these findings.

PMID- 16445286
TI  - Spectral, kinetic, and thermodynamic properties of Cu(I) and Cu(II) binding by
      methanobactin from Methylosinus trichosporium OB3b.
AB  - To examine the potential role of methanobactin (mb) as the extracellular
      component of a copper acquisition system in Methylosinus trichosporium OB3b, the
      metal binding properties of mb were examined. Spectral (UV-visible, fluorescence,
      and circular dichroism), kinetic, and thermodynamic data suggested copper
      coordination changes at different Cu(II):mb ratios. Mb appeared to initially bind
      Cu(II) as a homodimer with a comparatively high copper affinity at Cu(II):mb
      ratios below 0.2, with a binding constant (K) greater than that of EDTA (log K =
      18.8) and an approximate DeltaG degrees of -47 kcal/mol. At Cu(II):mb ratios
      between 0.2 and 0.45, the K dropped to (2.6 +/- 0.46) x 10(8) with a DeltaG
      degrees of -11.46 kcal/mol followed by another K of (1.40 +/- 0.21) x 10(6) and a
      DeltaG degrees of -8.38 kcal/mol at Cu(II):mb ratios of 0.45-0.85. The kinetic
      and spectral changes also suggested Cu(II) was initially coordinated to the 4
      thiocarbonyl-5-hydroxy imidazolate (THI) and possibly Tyr, followed by reduction
      to Cu(I), and then coordination of Cu(I) to 4-hydroxy-5-thiocarbonyl imidazolate
      (HTI) resulting in the final coordination of Cu(I) by THI and HTI. The rate
      constant (k(obsI)) of binding of Cu(II) to THI exceeded that of the stopped flow
      apparatus that was used, i.e., >640 s(-)(1), whereas the coordination of copper
      to HTI showed a 6-8 ms lag time followed by a k(obsII) of 121 +/- 9 s(-)(1). Mb
      also solubilized and bound Cu(I) with a k(obsI) to THI of >640 s(-)(1), but with
      a slower rate constant to HTI (k(obsII) = 8.27 +/- 0.16 s(-)(1)), and appeared to
      initially bind Cu(I) as a monomer.

PMID- 16445285
TI  - Kinetics of anesthetic-induced conformational transitions in a four-alpha-helix
      bundle protein.
AB  - Inhaled anesthetics are thought to alter the conformational states of Cys-loop
      ligand-gated ion channels (LGICs) by binding within discrete cavities that are
      lined by portions of four alpha-helical transmembrane domains. Because Cys-loop
      LGICs are complex molecules that are notoriously difficult to express and purify,
      scaled-down models have been used to better understand the basic molecular
      mechanisms of anesthetic action. In this study, stopped-flow fluorescence
      spectroscopy was used to define the kinetics with which inhaled anesthetics
      interact with (Aalpha(2)-L1M/L38M)(2), a four-alpha-helix bundle protein that was
      designed to model anesthetic binding sites on Cys-loop LGICs. Stopped-flow
      fluorescence traces obtained upon mixing (Aalpha(2)-L1M/L38M)(2) with halothane
      revealed immediate, fast, and slow components of quenching. The immediate
      component, which occurred within the mixing time of the spectrofluorimeter, was
      attributed to direct quenching of tryptophan fluorescence upon halothane binding
      to (Aalpha(2)-L1M/L38M)(2). This was followed by a biexponential fluorescence
      decay containing fast and slow components, reflecting anesthetic-induced
      conformational transitions. Fluorescence traces obtained in studies using
      sevoflurane, isoflurane, and desflurane, which poorly quench tryptophan
      fluorescence, did not contain the immediate component. However, these anesthetics
      did produce the fast and slow components, indicating that they also alter the
      conformation of (Aalpha(2)-L1M/L38M)(2). Cyclopropane, an anesthetic that acts
      with unusually low potency on Cys-loop LGICs, acted with low apparent potency on
      (Aalpha(2)-L1M/L38M)(2). These results suggest that four-alpha-helix bundle
      proteins may be useful models of in vivo sites of action that allow the use of a
      wide range of techniques to better understand how anesthetic binding leads to
      changes in protein structure and function.

PMID- 16445287
TI  - Red pool chlorophylls of photosystem I of the cyanobacterium Thermosynechococcus
      elongatus: a single-molecule study.
AB  - Photosystem I reaction centers of the cyanobacterium Thermosynechococcus
      elongatus have been investigated using single-molecule spectroscopy. Single
      molecule fluorescence emission spectra reveal a new fluorescence band located at
      745 nm. Fluorescence polarization spectroscopy and fluorescence autocorrelation
      analysis show that only a few chlorophylls are responsible for the photoemission
      from the Photosystem I trimer at low temperature. Intersystem crossing parameters
      of the red pool chlorophylls have been determined via fluorescence
      autocorrelation measurements. The triplet yield of the red chlorophylls is
      strongly reduced in comparison to chlorophyll a in solution. Strong quenching of
      the triplet state indicates that the red chlorophylls are located in close
      contact to carotenoids.

PMID- 16445288
TI  - Role of the C-terminal region of the B component of Methylosinus trichosporium
      OB3b methane monooxygenase in the regulation of oxygen activation.
AB  - The effects of the C-terminal region of the B component (MMOB) of soluble methane
      monooxygenase (sMMO) from Methylosinus trichosporium OB3b on steady-state
      turnover, the transient kinetics of the reaction cycle, and the properties of the
      sMMO hydroxylase (MMOH) active site diiron cluster have been explored. MMOB is
      known to have many profound effects on the rate and specificity of sMMO. Past
      studies have revealed specific roles for the well-folded core structure of MMOB
      as well as the disordered N-terminal region. Here, it is shown that the
      disordered C-terminal region of MMOB also performs critical roles in the
      regulation of catalysis. Deletion mutants of MMOB missing 5, 8, and 13 C-terminal
      residues cause progressive decreases in the maximum steady-state turnover number,
      as well as lower apparent rate constants for formation of the key reaction cycle
      intermediate, compound Q. It is shown that this latter effect is actually due to
      a decrease in the rate constant for formation of an earlier intermediate,
      probably the hydroperoxo species, compound P. Moreover, the deletions result in
      substantial uncoupling at or before the P intermediate. It is proposed that this
      is due to competition between slow H(2)O(2) release from one of the intermediates
      and the reaction that carries this intermediate on to the next step in the cycle,
      which is slowed by the mutation. Electron paramagnetic resonance (EPR) studies of
      the hydroxylase component (MMOH) in the mixed valent state suggest that
      complexation with the mutant MMOBs alters the electronic properties of the diiron
      cluster in a manner distinct from that observed when wild-type MMOB is used.
      Active site structural changes are also suggested by a substantial decrease in
      the deuterium kinetic isotope effect for the reaction of Q with methane thought
      to be associated with a decrease in quantum tunneling in the C-H bond breaking
      reaction. Thus, the surface interactions between MMOH and MMOB that affect
      substrate oxidation and its regulation appear to require the complete MMOB C
      terminal region for proper function.

PMID- 16445289
TI  - A reinvestigation of the secondary structure of functionally active vSGLT, the
      vibrio sodium/galactose cotransporter.
AB  - The bacterial Na(+)/galactose cotransporter vSGLT of Vibrio parahaemolyticus is a
      member of the sodium:solute symporter family (SSS). Previous studies using
      electron microscopy have shown that vSGLT is a monomeric protein. Computational
      and experimental topological analyses have consistently indicated that this
      protein possesses 14 transmembrane alpha-helices. Our previous study using
      attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR)
      to quantitate secondary structure content had indicated, in contrast, an alpha
      helical content of only 35%, too little to be consistent with the 14-span model
      [le Coutre, J., et al. (2002) Biochemistry 41, 8082-6]. ATR-FTIR had also
      indicated that upon binding of Na(+) and d-galactose, the alpha-helical content
      increased to 53%. Here we revisit the vSGLT secondary structural distribution
      using an alternative approach, ultraviolet circular dichroism spectropolarimetry
      (CD), which is highly accurate in determining the alpha-helical content of a
      protein in solution. CD spectra were obtained from actively functional, soluble
      vSGLT and, as an internal check, from a fusion protein of vSGLT and the beta
      barrel green fluorescent protein (GFP). Far-UV CD of vSGLT indicates a
      predominating 85% alpha-helical content, and an absence of beta-strands. Far-UV
      CD of the vSGLT-GFP fusion corroborates this profile, indicating an equivalent
      alpha-helical content, and a beta-strand content consistent with the GFP
      contribution. No detectable substrate-induced macroscopic changes in secondary
      structure are apparent in the far UV. In the near UV, increases in positive CD
      intensity occur in a stepwise manner with added substrates, implying changing
      environments of aromatic amino acid residues. CD thus confirms the current 14
      transmembrane span model of vSGLT and reveals distinct substrate-induced
      conformational changes. The high percentage of alpha-helical structure found
      requires, when considered in the context of membrane topology, that nearly a
      third of the total alpha-helical fraction lies in extramembrane domains, which
      distinguishes this cotransporter from the unrelated lactose and glycerol 3
      phosphate transporters.

PMID- 16445290
TI  - Resonance Raman study of Bacillus subtilis NO synthase-like protein: similarities
      and differences with mammalian NO synthases.
AB  - Bacterial NO synthase (NOS)-like proteins such as that from Bacillus subtilis
      (bsNOS) share a high degree of structural homology with the oxygenase domain of
      mammalian NOSs (mNOSs), but biochemical studies have yet failed to establish that
      they are specifically capable of producing NO. To better understand the actual
      function and role of bacterial NOSs, the structure and environment of bsNOS heme
      were examined with resonance Raman (RR) and ATR-FTIR spectroscopies. We analyzed
      the structural effects of l-arginine (Arg) and tetrahydrobiopterin (H(4)B)
      binding on several key complexes (ferric, ferrous, ferrous-CO, and ferric-NO) and
      characterized the bonding properties of the proximal cysteine ligand. While our
      study fully confirms the similarity between bsNOS and mNOS heme pocket
      structures, our results also highlight important differences. (i) Contrary to
      other NOSs, resting native ferric bsNOS exhibits an exclusive five-coordinate
      high-spin iron status. (ii) The nu(Fe)(-)(CO) and nu(CO) mode frequencies of the
      bsNOS Fe(II)CO complexes indicate a weaker electrostatic interaction between Arg
      and CO. (iii) bsNOS is characterized by a stronger Fe-S bond (nu(Fe)(-)(S) = 342
      cm(-)(1)), a lower nu(4) frequency, and a negative shift in the nu(Fe)(
      )(CO)/nu(CO) correlation. (iv) The effects of H(4)B on bsNOS heme structure are
      minor compared to the ones reported on mNOS. These results suggest distinct
      distal heme environments between mNOS and bsNOS, greater electron-donation
      properties of bsNOS cysteine proximal ligand, and the absence of a significant
      influence of H(4)B on bsNOS heme properties. These subtle structural differences
      may reflect changes in the chemistry and physiological role of bacterial NOSs.

PMID- 16445291
TI  - Nonphotochemical quenching of chlorophyll fluorescence in Chlamydomonas
      reinhardtii.
AB  - Unlike plants, Chlamydomonas reinhardtii shows a restricted ability to develop
      nonphotochemical quenching upon illumination. Most of this limited quenching is
      due to state transitions instead of DeltapH-driven high-energy state quenching,
      qE. The latter could only be observed when the ability of the cells to perform
      photosynthesis was impaired, either by lowering temperature to approximately 0
      degrees C or in mutants lacking RubisCO activity. Two main features were
      identified that account for the low level of qE in Chlamydomonas. On one hand,
      the electrochemical proton gradient generated upon illumination is apparently not
      sufficient to promote fluorescence quenching. On the other hand, the capacity to
      transduce the presence of a DeltapH into a quenching response is also
      intrinsically decreased in this alga, when compared to plants. The possible
      mechanism leading to these differences is discussed.

PMID- 16445292
TI  - A novel protein kinase CK2 substrate indicates CK2 is not directly stimulated by
      polyamines in vivo.
AB  - The activity of the protein kinase (CK2) is enhanced in vitro by the binding of
      polyamines to the CK2beta regulatory subunit. The overexpression of ornithine
      decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, also
      elevates CK2 kinase activity in primary keratinocytes and tissues of K6/ODC
      transgenic mice. In an effort to better characterize the mechanisms by which
      polyamines may affect CK2 in vivo, we constructed a transfectable CK2 substrate
      cDNA consisting of the enhanced green fluorescence protein appended with a
      canonical CK2 phosphorylation sequence (EGFP-S). In contrast to unmodified EGFP,
      the EGFP-S protein was extensively phosphorylated by CK2, and this
      phosphorylation was stimulated by the polyamine spermine in a dose-dependent
      manner. The in vivo phosphorylation of EGFP-S was examined in cell lines which
      inducibly express either wild-type CK2 holoenzyme or a CK2 holoenzyme which
      contains activating mutations in the polyamine-binding region of its CK2beta
      regulatory subunit. Neither the overexpression of ODC in either cell line nor the
      mutation of the CK2beta subunit conferred an increase in CK2 kinase activity as
      measured by the in vivo phosphorylation of EGFP-S. Rather, our data indicate that
      polyamines increase total CK2 kinase activity through increases in steady-state
      levels of both CK2alpha and CK2beta subunits. The overexpression of ODC resulted
      in a 3-fold increase in steady-state levels of both exogenous and endogenous CK2
      transcripts but did not increase the half-life of wild-type or mutated CK2
      protein. These data suggest that the regulation of intracellular CK2 by the
      polyamines may occur through mechanisms distinct from the direct stimulation of
      CK2 by polyamines in vitro as previously described.

PMID- 16445293
TI  - Alpha-RgIA: a novel conotoxin that specifically and potently blocks the
      alpha9alpha10 nAChR.
AB  - The alpha9 and alpha10 nicotinic acetylcholine receptor (nAChR) subunits assemble
      to form the alpha9alpha10 nAChR subtype. This receptor is believed to mediate
      cholinergic synaptic transmission between efferent olivocochlear fibers and the
      hair cells of the cochlea. In addition alpha9 and/or alpha10 expression has been
      described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes, and
      the pars tuberalis of the pituitary. Specific antagonists that selectively block
      the alpha9alpha10 channel could be valuable tools for elucidating its role in
      these diverse tissues. This study describes a novel alpha-conotoxin from the
      Western Atlantic species Conus regius, alpha-conotoxin RgIA (alpha-RgIA), that is
      a subtype specific blocker of the alpha9alpha10 nAChR. alpha-RgIA belongs to the
      alpha4/3 subfamily of the alpha-conotoxin family; sequence and subtype
      specificity comparisons between alpha-RgIA and previously characterized alpha4/3
      toxins indicate that the amino acids in the C-terminal half of alpha-RgIA are
      responsible for its preferential inhibition of the alpha9alpha10 nAChR subtype.

PMID- 16445294
TI  - Bimodal loop-loop interactions increase the affinity of RNA aptamers for HIV-1
      RNA structures.
AB  - Multiple loop-loop interactions between adjacent RNA hairpins regulate gene
      expression in different organisms. To demonstrate that such natural interactions
      could be mimicked for generating RNA ligands that are able to recognize
      simultaneously at least two structured RNA targets, a double kissing complex
      model was designed. The target consisted of two HIV-1 transactivating responsive
      (TAR) RNA variants, BRU and MAL, connected by a non-nucleotidic linker. The
      double ligand was generated by combining the corresponding hairpin aptamers,
      R06BRU and R06MAL, identified previously by in vitro selection [Duconge, F., and
      Toulme, J. J (1999) RNA 5, 1605-1614]. The resulting interaction was analyzed by
      thermal denaturation monitored by UV spectroscopy, electrophoretic mobility shift
      assays (EMSAs), and surface plasmon resonance (SPR) experiments. The bimodal
      complex was characterized by a binding equilibrium constant increased by at least
      1 order of magnitude compared to that of the complexes between the individual
      parent hairpins. This resulted from a slower dissociation rate. We then made use
      of such a strategy for targeting two structured functional motifs of the folded
      5' untranslated region (5'UTR) of HIV-1. Two bivalent RNA ligands were designed
      that targeted simultaneously the TAR and dimerization initiation site (DIS)
      hairpins or the TAR and poly(A) ones. The results show that these ligands also
      displayed enhanced affinity for their target compared to the individual
      molecules. The work reported here suggests that bimodal structured RNA ligands
      might provide a way of increasing the affinity of aptamers for folded RNA
      targets.

PMID- 16445295
TI  - Post-translational modifications of human thrombin-activatable fibrinolysis
      inhibitor (TAFI): evidence for a large shift in the isoelectric point and reduced
      solubility upon activation.
AB  - Thrombin-activable fibrinolysis inhibitor (TAFI) is distinct from pancreatic
      procarboxypeptidase B in several ways. The enzymatic activity of TAFIa is
      unstable and decays with a half-life of a few minutes. During this study, we
      observed that (i) the isoelectric point (pI) of TAFI shifts dramatically from pH
      5 toward pH 8 upon activation and (ii) TAFIa is significantly less soluble than
      TAFI. The structural bases for these observations were investigated by
      characterizing all post-translational modifications, including attached glycans
      and disulfide connectivity. The analyses revealed that all five potential N
      glycosylation sites were utilized including Asn22, Asn51, Asn63, Asn86 (located
      in the activation peptide), and Asn219 (located in the catalytic domain). Asn219
      was also found in an unglycosylated variant. Four of the glycans, Asn51, Asn63,
      Asn86, and Asn219 displayed microheterogeneity, while the glycan attached to
      Asn22 appeared to be homogeneous. In addition, bisecting GlcNAc attached to the
      trimannose core was detected, suggesting an origin other than the liver.
      Monosaccharide composition and LC-MS/MS analyses did not produce evidence for O
      glycosylation. TAFI contains eight cysteine residues, of which two, Cys69 and
      Cys383, are not involved in disulfides and contain free sulfhydryl groups. The
      remaining six cystines form disulfides, including Cys156-Cys169, Cys228-Cys252,
      and Cys243-Cys257. This pattern is homologous to pancreatic procarboxypeptidase
      B, and it is therefore unlikely that permutations in the cysteine connectivity
      are responsible for the enzymatic instability. LC-MS/MS analyses covering more
      than 90% of the TAFI amino acid sequence revealed no additional modifications.
      When these results are taken together, they suggest that the inherent instability
      of TAFIa is not caused by post-translational modifications. However, after
      activation, TAFIa loses 80% of the attached glycans, generating a large shift in
      pI and a propensity to precipitate. These changes are likely to significantly
      affect the properties of TAFIa as compared to TAFI.

PMID- 16445299
TI  - Bayesian methods for evidence synthesis in cost-effectiveness analysis.
AB  - Recently, health systems internationally have begun to use cost-effectiveness
      research as formal inputs into decisions about which interventions and programmes
      should be funded from collective resources. This process has raised some
      important methodological questions for this area of research. This paper
      considers one set of issues related to the synthesis of effectiveness evidence
      for use in decision-analytic cost-effectiveness (CE) models, namely the need for
      the synthesis of all sources of available evidence, although these may not 'fit
      neatly' into a CE model. Commonly encountered problems include the absence of
      head-to-head trial evidence comparing all options under comparison, the presence
      of multiple endpoints from trials and different follow-up periods. Full evidence
      synthesis for CE analysis also needs to consider treatment effects between
      patient subpopulations and the use of nonrandomised evidence. Bayesian
      statistical methods represent a valuable set of analytical tools to utilise
      indirect evidence and can make a powerful contribution to the decision-analytic
      approach to CE analysis. This paper provides a worked example and a general
      overview of these methods with particular emphasis on their use in economic
      evaluation.

PMID- 16445301
TI  - Too important to ignore: informal caregivers and other significant others.

PMID- 16445300
TI  - Costs of irritable bowel syndrome in the UK and US.
AB  - Irritable bowel syndrome (IBS) is one of the most common functional
      gastrointestinal disorders, with an estimated prevalence rate in the general
      population of 10-15% in industrialised countries. Although IBS is not a life
      threatening disease, it contributes significantly to a large segment of
      healthcare resource consumption. This review provides an overview of studies
      addressing the direct and indirect costs of IBS in the US and the UK. A
      systematic literature search was conducted in MEDLINE and the Cochrane library;
      additionally, all reference lists covering the years from 1960 to May 2004 were
      scanned. Twenty-four publications for the US and the UK, published between 1991
      and 2003, were identified: 6 were excluded, 18 were included. Data for the UK, US
      and UK + US were reported in 5, 11 and 2 publications, respectively. Total direct
      cost estimates per patient per year ranged from US 348 dollars to US 8750 dollars
      (calculated for year 2002). The average number of days off work per year because
      of IBS was between 8.5 and 21.6; indirect costs ranged from US 355 dollars to US
      3344 dollars. The total costs and cost components of IBS are influenced by
      several factors: features of the investigated patient group (age, limitation to
      healthcare seekers or all IBS patients, comorbidity, severity of symptoms),
      database used, method of data collection (retrospective or prospective, varying
      cost components, time-point of data collection in relation to index-date of IBS
      diagnosis, method of cost calculation [incidence or prevalence based]) and
      different healthcare systems in the US and the UK. These factors led to the
      incomparability of published data, thus no comprehensive picture can be drawn of
      the total costs related to IBS in the UK and US. Data underline the magnitude of
      the economic impact of IBS in the UK and US, which is increased by a factor of
      1.1-6.0, compared with matched non-IBS control groups. IBS contributes both
      direct and indirect costs to the total healthcare bill. Further studies should
      take influencial factors into account and report related data carefully in order
      to provide useful and comparable published cost data. Additionally, further
      research on the cost effectiveness of diagnostic procedures and therapies in IBS
      is required to define strategies to help IBS patients improve their quality of
      life and reduce related costs.

PMID- 16445302
TI  - Incorporating carer effects into economic evaluation.
AB  - BACKGROUND: Despite great interest in the development of methods used in the
      economic evaluation of health technologies, the effects of carer costs and
      quality of life (QOL) on the cost effectiveness of treatments has not been widely
      explored. Yet carer effects are clearly evident in the literature and relevant to
      the perspective of many published economic evaluations. OBJECTIVE: To examine
      whether patient QOL is associated with carer time and carer QOL. METHODS: We used
      two datasets to investigate carer effects. Firstly, we used 40,312 cases from the
      Health Outcomes Data Repository (HODaR) to assess the relationship between
      patient utility, using the EuroQoL (EQ)-5D, and the number of days care needed
      from friends and relatives. The stability of the relationship across patient
      subgroups was assessed by replicating the analysis in ten disease groups.
      Secondly, we used 64 cases from a study of patients with Alzheimer's disease and
      their primary carer. These data allowed us to estimate the relationships between
      patient and carer utility, using the EQ-5D, and patient utility and carer burden
      using the Community Dementia Quality of Life Profile (CDQLP). RESULTS: For carer
      time, a linear model showed that each 0.1-point reduction in patient utility was
      associated with a 2.5-day increase in carer time over a 6-week period. A more
      general model, based on EQ-5D domain scores, was better specified and showed that
      decreased functioning within each domain is associated with increased carer time.
      Problems with self-care and usual activities have the greatest impact on carer
      time. These models do not appear to be stable across different disease groups.
      For carer utility, the relationships between carer and patient utility have low
      explanatory power and are poorly specified. A clearer relationship is shown
      between carer burden and utility, such that when sociodemographic covariates are
      introduced, the relationship reaches conventional levels of statistical
      significance (p < 0.05). CONCLUSIONS: The preliminary work described here shows
      that improving patient QOL may reduce the need for carer time and improve carer
      QOL. Incorporating such effects into economic evaluations will change cost-per
      QALY estimates, with the size of reduction dependent on the domains of health
      affected by treatment. Clinical studies need to capture carer data so that we can
      better understand these effects, and how they impact on economic evaluation.

PMID- 16445303
TI  - Interstitial Cystitis: Cost, treatment and co-morbidities in an employed
      population.
AB  - INTRODUCTION: Recent literature indicates that interstitial cystitis (IC) may
      affect 20% of women and a smaller proportion of men, although many individuals
      with IC may be misdiagnosed or remain undiagnosed. Factors that can contribute to
      the cost of IC include medical and drug utilisation related to treatment and
      diagnosis of IC and associated conditions (e.g. depression), as well as employee
      work loss. This study assesses the direct medical cost and indirect cost of work
      loss for IC patients in the first year after diagnosis, and evaluates IC
      treatment patterns and prevalence of co-morbidities. METHODS: Data for patients
      under the age of 65 years with at least one diagnosis of IC (n = 749) were drawn
      from a de-identified, administrative database of approximately 2 million
      beneficiaries that included medical, drug and disability claims for 1999-2002. A
      2 : 1 matched control sample of patients without an IC diagnosis (non-IC sample)
      was randomly selected based on patient characteristics. Indirect costs were
      calculated from a subgroup of 152 IC patients (plus their matched controls) who
      had disability information available. Costs incurred in the first year after IC
      diagnosis and co-morbidities were compared between IC patients and the non-IC
      sample, with the difference in costs defined as 'excess costs' of IC patients.
      Treatment patterns were profiled in the 2 months following initial diagnosis of
      IC. Descriptive statistics are presented. A multivariate two-part model was
      applied to estimate the IC direct medical cost, indirect cost and total cost to
      adjust for observed patient demographics and co-morbidities. Statistical
      significance was evaluated by the bootstrap method. RESULTS: The average IC
      patient had 130% higher direct costs (p < 0.05) and the average IC employee
      patient had 84% higher indirect costs than the average non-IC control individual.
      IC patients also had a higher diagnostic prevalence of prostatitis (relative risk
      [RR] = 40.0), endometriosis (RR = 7.4), vulvodynia (RR = 6.9), chronic pelvic
      pain (RR = 5.8) and urinary tract infections (RR = 5.1) [all p < 0.05]. IC
      patients were also more likely to report depression (RR = 2.8) and anxiety (RR =
      4.5 ) than non-IC controls (all p < 0.05). Seventeen percent of IC patients
      received pentosan polysulfate therapy, the only US FDA-approved oral drug therapy
      indicated for treating IC, within the first 2 months after diagnosis. Of these
      patients, 69% received at least one 'other' drug from the non-approved oral
      medications studied. Approximately one-third of IC patients received only 'other'
      drug therapies, and almost half of IC patients received no drug treatment within
      the first 2 months after the initial diagnosis. CONCLUSIONS: IC is a costly
      disease associated with co-morbidities. Following diagnosis, patients with IC are
      commonly untreated or treated with non-approved drug therapies. It is possible
      that more accurate diagnosis and earlier and more appropriate treatment of IC
      would lead to better management (or even prevention) of co-morbidities and reduce
      healthcare costs, and this should be investigated in future studies.

PMID- 16445304
TI  - Evaluation of the cost effectiveness of sirolimus versus tacrolimus for
      immunosuppression following renal transplantation in the UK.
AB  - INTRODUCTION: Immunosuppressive therapy is required to prevent graft rejection.
      Calcineurin inhibitors such as tacrolimus are paradoxically toxic to the kidney,
      whereas sirolimus (rapamycin; Rapamune) is not generally associated with the
      nephrotoxicity of CNIs. The purpose of this study was to evaluate the relative
      cost utility of sirolimus versus tacrolimus for the primary prevention of graft
      rejection in renal transplant recipients in the UK. METHODS: A stochastic
      simulation model was constructed using clinical trial and observational data
      comparing the two treatments. Time duration was up to 20 years. Costs were from a
      UK NHS perspective, valued at 2003 prices and discounted at 6%. Benefits were
      discounted at 1.5%. Simulated events included patient and graft survival,
      haemodialysis, peritoneal dialysis, re-transplants and acute rejection. Costs
      were summed for events and various maintenance therapies. Utility was
      differentially accredited depending upon survival and using the alternative renal
      replacement therapies. Outcome was predicted using post-transplant creatinine
      levels up to 3 years. Extensive statistical economic and sensitivity analyses
      were undertaken. RESULTS: Over the 10-year horizon, sirolimus gained 0.72 years
      (discounted) of functioning graft over tacrolimus, resulting in an incremental
      cost per year of functioning graft that was dominant. Over a 20-year time
      horizon, the cost effectiveness of sirolimus over tacrolimus further improved
      with an average discounted gain in years of a functioning graft of 1.8 years,
      resulting in an incremental cost-utility ratio that was also dominant. The number
      of haemodialysis events was 48,243 for sirolimus recipients versus 127,829 for
      those receiving tacrolimus and peritoneal dialysis events 40,872 versus 105,249,
      respectively. Similar values were obtained when real-life observational data on
      tacrolimus use in Cardiff, Wales were entered into the model. Using data from
      Cardiff, sirolimus remained dominant over tacrolimus under all scenarios.
      CONCLUSION: Our study suggests that sirolimus may be more cost effective than
      tacrolimus for the primary prevention of graft rejection in renal transplant
      recipients in the UK. Sirolimus was economically 'dominant' under almost all
      scenarios investigated. This finding was robust using statistical economic
      analysis and univariate sensitivity analysis.

PMID- 16445307
TI  - Eating disorders in the male athlete.
AB  - Eating disorders do occur in male athletes. They are less prominent than in
      female athletes, and therefore in danger of being missed. The high-risk sports
      fall into the same categories as with females: aesthetic sports, sports in which
      low body fat is advantageous, such as cross-country and marathon running, and
      sports in which there is a need to "make weight", including wrestling and horse
      racing. Athletic involvement may foster the development of an eating disorder.
      Some male athletes, in their preoccupation with body image, will abuse anabolic
      steroids. While sports participation may contribute to the aetiology of an eating
      disorder, the converse is also true. Exercise may be used as therapy for some
      cases of eating disorder. In order to adequately treat eating disorders in the
      male athlete, it is first essential to identify cases. Psychoeducation of
      athletes, their families, coaches and trainers is an important first step.
      Counselling an athlete to pursue a sport appropriate to his body type, or to
      leave his sport behind altogether (an unpopular recommendation from a coach's
      perspective) can be important to treatment. Treatment of co-morbid psychiatric
      conditions is essential. Treatment can be structured using a biopsychosocial
      approach, and all appropriate modalities of therapy, including individual, family
      and group, as well as psychopharmacotherapy, where appropriate, should be
      applied.

PMID- 16445306
TI  - Economic evaluation of rivastigmine in patients with Parkinson's disease
      dementia.
AB  - BACKGROUND: The positive results of a randomised clinical trial of rivastigmine
      in patients with dementia associated with Parkinson's disease have been published
      recently. Patient-level healthcare utilisation data were also collected, and this
      report is the economic evaluation based on these data. OBJECTIVE: To determine
      the cost effectiveness of rivastigmine 3-12 mg/day in patients in whom mild to
      moderate dementia developed at least 2 years after they received a clinical
      diagnosis of Parkinson's disease. METHODS: A cost-effectiveness analysis was
      performed by applying Canadian and UK cost weights (year 2004 values) to
      healthcare utilisation data collected prospectively during a randomised, double
      blind, multinational, 24-week trial of rivastigmine 3-12 mg/day (n = 362) versus
      placebo (n = 179). Patients were > or =50 years of age, had a Mini-Mental State
      Examination (MMSE) score of between 20 and 24 and had contact with a responsible
      caregiver at least 3 days a week.Quality-adjusted survival time, transformed from
      MMSE scores, was the measure of effectiveness. Caregiver costs included paid and
      unpaid time, and direct costs included concomitant medications, outpatient care,
      hospitalisations, long-term care and study medications. Analysis was conducted
      from a societal perspective with a time horizon of 24 weeks. RESULTS: Consistent
      with the improvement in clinical outcomes, there was an observed increase in
      quality-adjusted survival time in the rivastigmine arm of 2.81 quality-adjusted
      life-days (two-sided p-value 0.13 [90% CI -0.243, 5.86]). Using Canadian price
      weights, there was an observed increase in cost in the rivastigmine arm of Can
      55.76 dollars(two-sided p-value 0.98 [90% CI -3431, 3543]), with a resulting
      incremental cost-effectiveness ratio of Can 7429 dollars per QALY. Using UK price
      weights, there was an observed decrease in cost in the rivastigmine arm of pound
      26.18 (two-sided p-value 0.99 [90% CI -2407, 2355]). CONCLUSION: Although no
      between-treatment differences in cost were seen, the small sample size, highly
      variable cost distributions and short time horizon prevent us from making strong
      conclusions with regard to the effect of rivastigmine on total costs and, by
      inference, on cost effectiveness.

PMID- 16445305
TI  - Cost effectiveness of bemiparin sodium versus unfractionated heparin and oral
      anticoagulants in the acute and long-term treatment of deep vein thrombosis.
AB  - INTRODUCTION: Low-molecular-weight heparins (LMWHs) are at least as effective and
      well tolerated as unfractionated heparin (UFH) in the treatment of deep vein
      thrombosis (DVT), offering easier administration and obviating the need for
      anticoagulant monitoring, but have a higher acquisition cost than UFH. OBJECTIVE:
      To quantify the potential economic impact of two regimens of subcutaneous
      bemiparin 115 IU/kg/day for 7-10 days (plus oral anticoagulants [OAC] or followed
      by long-term bemiparin 3500IU) versus dose-adjusted intravenous UFH for 7 days
      plus OAC for 3 months in the acute and long-term treatment of DVT. The
      representative patient was a 62-year-old, 77 kg male with proximal DVT of the
      lower limbs. METHODS: A cost-effectiveness analysis was performed using a
      decision-tree modelling approach. The results were expressed in terms of costs
      (euro, 2002 values) and incremental cost effectiveness. The treatment costs
      (hospital stay, physician services, drug administration) and costs incurred due
      to complications (pulmonary embolism, recurrent DVT, bleeding events,
      thrombocytopenia and deaths) during the 3-month study period were considered for
      the primary analysis. Life expectancy and QALYs were considered for the secondary
      analysis. The study was performed in the setting of the Spanish National Health
      System. RESULTS: Bemiparin plus OAC or long-term bemiparin for 3 months provided
      net cost savings of euro 769 and euro 908 per patient, respectively, compared
      with UFH plus OAC (UFH plus OAC euro 4128 vs bemiparin plus OAC euro 3359 vs long
      term bemiparin euro 3220). Bemiparin plus OAC and long-term bemiparin for 3
      months were calculated to avoid 27 and 7 additional VTE events, respectively, per
      1000 patients treated. Bemiparin plus OAC or long-term bemiparin increased
      quality-adjusted life expectancy by approximately 1.72 and 0.74 years,
      respectively, compared with UFH plus OAC. The univariate sensitivity analysis
      supported the cost effectiveness of bemiparin in all the ranges tested for
      complications and costs. CONCLUSIONS: Our model suggests that bemiparin plus OAC
      or long-term bemiparin for 3 months may be dominant strategies over UFH plus OAC
      in the treatment of DVT from the Spanish National Health System perspective,
      offering better outcomes and cost savings. Long-term bemiparin may be a cost
      neutral alternative to bemiparin plus OAC.

PMID- 16445308
TI  - Non-traumatic bicycle injuries : a review of the literature.
AB  - Bicycle riding is a popular form of recreation, fitness and transportation in
      many areas of the world. Traumatic injuries associated with bicycle riding have
      been documented and intervention strategies have been successful. This has not
      been the case for non-traumatic injuries. The prevalence of non-traumatic bicycle
      injuries can be as high as 85%. The most common sites for non-traumatic cycling
      related injuries include the knee, neck/shoulder, hands, buttock and perineum.
      Two categories of injuries that may have the greatest impact on disability
      include ulnar and median nerve palsy, and erectile dysfunction. Injury prevention
      strategies have been proposed to reduce non-traumatic injuries but these
      strategies remain untested.

PMID- 16445309
TI  - A review of physical activity patterns in pregnant women and their relationship
      to psychological health.
AB  - Regular physical activity contributes positively to physical and psychological
      health. Adverse consequences of inactivity may be an especially important problem
      among pregnant women. Up to 60% are inactive during pregnancy. This review found
      consistent evidence that physical activity is reduced during pregnancy; however,
      few investigators have sought to quantify physical activity patterns among
      pregnant women using well validated measures. Some of the barriers to physical
      activity during pregnancy, such as depression, anxiety and fatigue, have been
      shown to be attenuated by regular exercise performed by non-pregnant samples.
      There is a need to better understand the relationships between these factors and
      physical activity during pregnancy. Available retrospective and prospective
      results suggest that both leisure time and work-related physical activities are
      decreased across pregnancy. Intensity and duration decrease both during pregnancy
      compared with pre-pregnancy and in the third trimester compared with the first.
      There is a need for well designed longitudinal investigations that document
      pregnancy-related changes in physical activity at frequent intervals during
      pregnancy using validated and more precise measures of physical activity.
      Reductions in physical activity and a worsening mood are common during pregnancy.
      If the relationship between physical inactivity and mood disturbances is indeed
      observed and maintained during pregnancy, then decreases in physical activity in
      the third trimester would be expected to result in a worsening mood. In recent
      years, increased attention has been paid to antenatal mood disturbances, and this
      research has yielded a host of important findings. Prior correlational and
      experimental research with non-pregnant samples has demonstrated a consistent
      relationship between physical inactivity and mood disturbances. Whether this
      relationship occurs among pregnant women and/or is maintained as women progress
      during pregnancy is uncertain. Prior investigations have revealed that there is
      higher rate of mood disturbance during pregnancy than following pregnancy but
      little is known about the mechanisms that cause these mood disturbances. It is
      important to better understand changes in mood with pregnancy because mood
      disturbances can have major negative consequences for a pregnant woman. The major
      adverse consequences of depression among pregnant women are largely the same as
      those of non-pregnant individuals. Only six investigations have quantified the
      relationship between changes in physical activity and changes in mood during
      pregnancy. The available evidence suggests that inactivity is associated with
      worse mood. Additional research into this topic is warranted due to the limited
      number of published papers and the design and methodology limitations of these
      investigations.

PMID- 16445311
TI  - Possible stimuli for strength and power adaptation : acute metabolic responses.
AB  - The metabolic response to resistance exercise, in particular lactic acid or
      lactate, has a marked influence upon the muscular environment, which may enhance
      the training stimulus (e.g. motor unit activation, hormones or muscle damage) and
      thereby contribute to strength and power adaptation. Hypertrophy schemes have
      resulted in greater lactate responses (%) than neuronal and dynamic power
      schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors
      such as age, sex, training experience and nutrition may also influence the
      lactate responses to resistance exercise and thereafter, muscular adaptation.
      Although the importance of the mechanical and hormonal stimulus to strength and
      power adaptation is well recognised, the contribution of the metabolic stimulus
      is largely unknown. Relatively few studies for example, have examined metabolic
      change across neuronal and dynamic power schemes, and not withstanding the fact
      that those mechanisms underpinning muscular adaptation, in relation to the
      metabolic stimulus, remain highly speculative. Inconsistent findings and
      methodological limitations within research (e.g. programme design, sampling
      period, number of samples) make interpretation further difficult. We contend that
      strength and power research needs to investigate those metabolic mechanisms
      likely to contribute to weight-training adaptation. Further research is also
      needed to examine the metabolic responses to different loading schemes, as well
      as interactions across age, sex and training status, so our understanding of how
      to optimise strength and power development is improved.

PMID- 16445312
TI  - Parental correlates of physical activity in children and early adolescents.
AB  - This article is intended to unite the existing research on parental influences on
      children's physical activity behaviours in order to establish direction for
      future research and improve existing child physical activity intervention
      programmes. A comprehensive, 34-study review of parental correlates of child
      physical activity was conducted and six variables were examined. There were
      significant correlations found between parental support and child physical
      activity level. Results for an association between parental and child physical
      activity levels, however, were mixed. There were not enough studies to draw
      conclusions about single-parent families, family socioeconomic status and
      ethnicity. Finally, there were some weak inter- and intra-generational sex
      correlations, but these results were mostly inconclusive. Possible mechanisms,
      including parental support, modelling, shared activities, societal differences by
      generation, minority groups and genetics are discussed, and recommendations are
      made on translating experimental results into tangible intervention efforts
      essential for disease prevention through increased physical activity.

PMID- 16445313
TI  - Limb salvage following laser-assisted angioplasty for critical limb ischemia:
      results of the LACI multicenter trial.
AB  - PURPOSE: To evaluate the effectiveness of laser-assisted angioplasty for patients
      with critical limb ischemia (CLI) who were poor candidates for surgical
      revascularization. METHODS: A prospective registry at 14 sites in the US and
      Germany enrolled 145 patients with 155 critically ischemic limbs; the patients
      were poor candidates for bypass surgery owing to inadequate target vessel or
      saphenous vein, prohibitive cardiac disease, or significant comorbidities (ASA
      class 4). Additional comorbid risk factors included diabetes in 66%, hypertension
      in 83%, previous stroke in 21%, and myocardial infarction in 23%. Endovascular
      treatment included guidewire traversal and excimer laser angioplasty followed by
      balloon angioplasty with optional stenting. RESULTS: Occlusions were present in
      92% of limbs. A mean of 2.7+/-1.4 lesions were treated per limb; the total median
      treatment length was 11 cm (mean 16.2, range 0.2-123). Stents were implanted in
      45% of limbs. Procedural success, defined as <50% residual stenosis in all
      treated lesions, was seen in 86% of limbs. At 6-month follow-up, limb salvage was
      achieved in 110 (92%) of 119 surviving patients or 118 (93%) 127 limbs.
      CONCLUSION: Excimer laser-assisted angioplasty for CLI offers high technical
      success and limb salvage rates in patients unfit for traditional surgical
      revascularization.

PMID- 16445314
TI  - Endovascular cryotherapy accentuates the accumulation of the fibrillar collagen
      types I and III after percutaneous transluminal angioplasty in pigs.
AB  - PURPOSE: To investigate the effect of endovascular cryotherapy (Cryo) on the
      density of collagen types I (CI) and III (CIII), which are involved in the
      dynamic modulation of extracellular matrix (ECM) after percutaneous transluminal
      angioplasty (PTA). METHODS: Twenty-one juvenile farm swine and 10 miniswine
      underwent PTA of the femoral arteries with and without Cryo (-50 degrees C for 2
      minutes). Quantitative angiography, histomorphometry, and quantification of CI
      and CIII were performed at 1 week (n=7), 1 month (n=7), 3 months (n=7), and 6
      months (n=10). RESULTS: PTA decreased the minimal luminal diameter (MLD) (range
      3.48+/-0.18 to 4.2+/-0.39 mm) compared to baseline values (range 3.67+/-0.15 to
      4.59+/-0.23 mm), but the application of Cryo maintained the MLDs at preprocedural
      levels (range 3.88+/-0.31 to 4.58+/-0.21 mm). At the time of sacrifice, the MLDs
      were similar in PTA and Cryo-treated arteries, but the external elastic lamina
      was significantly greater after Cryo application (range 10.17+/-0.54 to 14.34+/
      0.76 mm2) than after PTA (range 8.69+/-0.70 to 11.77+/-0.73 mm2, p<0.05). Cryo
      did not alter the luminal area or prevent neointimal growth. A time-dependent
      increase of both CI and CIII was observed as early as 1 week after PTA, peaking
      at 3 months, and declining thereafter. Cryo accentuated this increase at all time
      points. CONCLUSION: The application of Cryo accentuates the accumulation of CI
      and CIII in PTA-treated femoral arteries. This effect may be of clinical
      relevance in the stabilization of peripheral atherosclerotic plaque.

PMID- 16445310
TI  - The roles of exercise-induced immune system disturbances in the pathology of heat
      stroke : the dual pathway model of heat stroke.
AB  - Heat stroke is a life-threatening condition that can be fatal if not
      appropriately managed. Although heat stroke has been recognised as a medical
      condition for centuries, a universally accepted definition of heat stroke is
      lacking and the pathology of heat stroke is not fully understood. Information
      derived from autopsy reports and the clinical presentation of patients with heat
      stroke indicates that hyperthermia, septicaemia, central nervous system
      impairment and cardiovascular failure play important roles in the pathology of
      heat stroke. The current models of heat stroke advocate that heat stroke is
      triggered by hyperthermia but is driven by endotoxaemia. Endotoxaemia triggers
      the systemic inflammatory response, which can lead to systemic coagulation and
      haemorrhage, necrosis, cell death and multi-organ failure. However, the current
      heat stroke models cannot fully explain the discrepancies in high core
      temperature (Tc) as a trigger of heat stroke within and between individuals.
      Research on the concept of critical Tc as a limitation to endurance exercise
      implies that a high Tc may function as a signal to trigger the protective
      mechanisms against heat stroke. Athletes undergoing a period of intense training
      are subjected to a variety of immune and gastrointestinal (GI) disturbances. The
      immune disturbances include the suppression of immune cells and their functions,
      suppression of cell-mediated immunity, translocation of lipopolysaccharide (LPS),
      suppression of anti-LPS antibodies, increased macrophage activity due to muscle
      tissue damage, and increased concentration of circulating inflammatory and
      pyrogenic cytokines. Common symptoms of exercise-induced GI disturbances include
      diarrhoea, vomiting, gastrointestinal bleeding, and cramps, which may increase
      gut-related LPS translocation. This article discusses the current evidence that
      supports the argument that these exercise-induced immune and GI disturbances may
      contribute to the development of endotoxaemia and heat stroke. When endotoxaemia
      can be tolerated or prevented, continuing exercise and heat exposure will elevate
      Tc to a higher level (>42 degrees C), where heat stroke may occur through the
      direct thermal effects of heat on organ tissues and cells. We also discuss the
      evidence suggesting that heat stroke may occur through endotoxaemia (heat
      sepsis), the primary pathway of heat stroke, or hyperthermia, the secondary
      pathway of heat stroke. The existence of these two pathways of heat stroke and
      the contribution of exercise-induced immune and GI disturbances in the primary
      pathway of heat stroke are illustrated in the dual pathway model of heat stroke.
      This model of heat stroke suggests that prolonged intense exercise suppresses
      anti-LPS mechanisms, and promotes inflammatory and pyrogenic activities in the
      pathway of heat stroke.

PMID- 16445315
TI  - Aneurysm sac re-expansion after thrombolysis.
AB  - PURPOSE: To present a case of delayed abdominal aortic aneurysm (AAA) re
      expansion after thrombolysis for endograft limb occlusion. CASE REPORT: A 68-year
      old man underwent AAA exclusion with an AneuRx stent-graft in 1999. Five years
      later, he developed right limb thrombosis of the endograft. He underwent right
      limb thrombolysis and AngioJet thrombectomy. The patient experienced abdominal
      and back pain during the procedure, and the aneurysm sac, which had remained
      reduced in size for several years, acutely re-expanded. The patient was managed
      conservatively. The fluid that accumulated in the sac was reabsorbed, and the AAA
      returned to its previous dimensions at 1-month follow-up. CONCLUSION: Symptomatic
      re-expansion of the aneurysm sac after AngioJet rheolytic thrombectomy may occur
      when the graft is stripped of neointima by the "power-pulse" spray of lytic
      agent, allowing serum to seep into the sac. Based on this experience, we advise
      caution when delivering thrombolytics using the AngioJet "power-pulse" spray mode
      in patients with a thrombosed stent-graft.

PMID- 16445316
TI  - Aortocaval fistula after stent-graft repair.
AB  - PURPOSE: To report an aortocaval fistula after stent-graft repair and the
      feasibility of interventional treatment. CASE REPORT: A 78-year-old man with a 61
      mm infrarenal aortic aneurysm (AA) was treated successfully with a Zenith
      bifurcated stent-graft. Three years later, the patient presented with
      deteriorating renal function and acute bronchial obstruction. Computed tomography
      showed an aortic diameter increased to 90 mm, dilatation of the inferior vena
      cava, and a distal type I endoleak. The patient's condition quickly deteriorated,
      and emergent imaging found a fistula with brisk flow between the aneurysm sac and
      the left iliac vein within a distal type I endoleak. During emergency
      endovascular repair, iliac extensions were implanted in the right common iliac
      artery and left external iliac artery. The left hypogastric artery was coil
      embolized to exclude flow into the aneurysm sac. After positioning the
      extensions, cardiac function improved, and the fistula was no longer palpable.
      The cardiac indices and renal function normalized, and he was discharged 20 days
      after admission. CONCLUSION: Aortocaval fistulas are a rare complication of AA
      stent-graft repair and may be successfully treated by interventional means.

PMID- 16445318
TI  - Pediatric penetrating renal artery trauma: stent-graft treatment with 2-year
      follow-up.
AB  - PURPOSE: To report the 2-year follow-up of a pediatric patient who underwent
      stent-graft repair for penetrating renal artery trauma. CASE REPORT: An 11-year
      old boy presented with a single anterior abdominal stab wound. He was
      normotensive (110/70 mmHg) but tachycardic (120 bpm). A focused abdominal
      sonogram for trauma revealed significant free intraperitoneal fluid. He underwent
      an urgent laparotomy, during which a minor liver injury was repaired. A large,
      nonpulsatile, non-expanding, left-sided retroperitoneal hematoma was identified
      but not explored. The boy remained hemodynamically unstable, so diagnostic
      angiography was performed. A single left proximal renal artery perforation was
      found. The lesion was treated with a 6x17-mm balloon-expandable stent-graft.
      Completion angiography demonstrated an excellent proximal and distal seal,
      without evidence of extravasation. The patient's condition stabilized, and he
      recovered completely. Serial renal duplex scans up to 2 years have documented
      normal renal artery blood flow and no migration of the stent-graft; the kidneys
      are equal in size. The serum creatinine level remains normal. CONCLUSION: In
      appropriately selected patients, transcatheter stent-graft placement is a
      promising new kidney salvage modality to treat renal artery injury in children.
      Serious concern remains regarding the placement of covered stents in the
      pediatric population, as the long-term durability and the adaptability of growing
      arteries to renal stents are not known.

PMID- 16445317
TI  - Procedural and clinical outcomes with catheter-based plaque excision in critical
      limb ischemia.
AB  - PURPOSE: To examine the safety and efficacy of catheter-based plaque excision as
      an alternative therapy to surgery, conventional angioplasty, and/or stenting in
      high-risk patients with critical limb ischemia (CLI). METHODS: Between August
      2003 and August 2004, a prospective evaluation was conducted of consecutive
      patients with CLI (Rutherford category>or=5) who were treated with endovascular
      plaque excision at 7 institutions. This study enrolled 69 patients (37 women;
      mean age 70+/-12 years, range 43-93) with CLI involving 76 limbs. Clinical
      outcomes were prospectively followed for 6 months. The primary endpoint was major
      adverse events (death, myocardial infarction, unplanned amputation, or repeat
      target vessel revascularization) at 30 days. Visible healing of ulcerated tissue,
      avoidance of any amputation, and performance of less extensive amputation than
      initially planned were also assessed. RESULTS: Procedural success was achieved in
      99% of cases. Major adverse events occurred in 1% of patients at 30 days and 23%
      at 6 months. The target lesion revascularization rate was 4%, and there were no
      unplanned limb amputations. Amputation was less extensive than initially planned
      or avoided altogether in 92% of patients at 30 days and 82% at 6 months.
      CONCLUSION: Catheter-based plaque excision is a safe and effective
      revascularization method for patients with CLI. These findings support further
      study of this modality as a singular or adjunctive endovascular therapy for limb
      salvage in CLI.

PMID- 16445319
TI  - Balloon dilation of a narrow distal aorta during bifurcated endograft placement:
      a reminder of the value of standard angioplasty techniques for increasing EVAR
      applicability.

PMID- 16445320
TI  - Arterial puncture site management after percutaneous transluminal procedures
      using a hemostatic wound dressing (Clo-Sur P.A.D.) versus conventional manual
      compression: a randomized controlled trial.
AB  - PURPOSE: To investigate the efficacy and safety of a novel hemostatic wound
      dressing designed for rapid hemostasis at arterial puncture sites. METHODS: Over
      a 15-month period, 209 consecutive patients were randomized to conventional
      manual compression (n=105) or the use of the Clo-Sur P.A.D. hemostatic device
      (n=104) after removal of the sheath. Puncture-related and device-related
      complications, time to hemostasis, time to ambulation, and patient and physician
      discomfort were recorded. RESULTS: In 209 patients, 21 (10.0%) puncture-related
      complications were observed, including 11 (5.3%) pseudoaneurysms, 9 (4.3%)
      hematomas, and 1 (0.5%) major bleeding complication. There was no significant
      difference (p=0.36) in complications between the hemostatic device (9/104, 8.7%)
      and the conventional group (12/105, 11.4%). In the hemostatic device group
      compared to the conventional group, respectively, the average time to hemostasis
      (13.6 versus 20.3 minutes; p<0.001), time to ambulation (6.5 versus 17.4 hours,
      p<0.001), patient discomfort (VAS 2.1 versus 4.7, p<0.001), and physician
      discomfort (VAS 3.8 versus 5.2, p<0.001) were significantly lower. Twenty (19%)
      sheath removals in the hemostatic device group were classified as a technical
      failure of the device. CONCLUSION: The use of this hemostatic wound dressing for
      arterial access site management after percutaneous vascular procedures
      significantly reduced the time to hemostasis, enabled early mobilization, and
      reduced patient discomfort without increasing the risk for complications compared
      to conventional manual compression. A high rate of technical failures, however,
      warrants further improvement before routine use can be recommended.

PMID- 16445321
TI  - Peripheral arterial procedures and postinterventional prophylaxis.

PMID- 16445322
TI  - Serum S-100B protein levels during and after successful carotid artery stenting
      or carotid endarterectomy.
AB  - PURPOSE: To characterize the course of S-100B serum levels, a reliable marker for
      cellular brain damage, in patients undergoing carotid artery stenting (CAS) or
      endarterectomy (CEA) for carotid artery stenosis compared to control groups
      undergoing hemithyroidectomy (HT) or coronary angiography (CA). METHODS: Forty
      six consecutive patients scheduled for revascularization of internal carotid
      artery (ICA) stenosis were included in the study. Fourteen patients (11 men;
      median age 70 years, interquartile range [IQR] 63-74) were selected for treatment
      with CAS, while CEA was performed in 31 patients (24 men; median age 68 years,
      IQR 54-78) during the same time period. Fourteen consecutive patients (8 men;
      median age 60 years, IQR 48-70) undergoing CA for suspected coronary heart
      disease and 14 patients (10 women; median age 36 years, IQR 26-54) undergoing HT
      for a single thyroid nodule served as controls. RESULTS: All procedures were
      completed successfully. During ICA clamping in CEA patients without postoperative
      neurological deficits, median S-100B serum levels transiently increased from 0.04
      to 0.26 ng/mL (p<0.01) and returned to baseline levels after declamping. Median S
      100B serum levels of CAS patients without neurological impairment remained at
      baseline values. No increase in S-100B levels occurred in either control group.
      Three CEA patients who suffered from neurological deficits (1 transient ischemic
      attack and 1 major stroke) showed sustained elevation of S-100B serum levels 6
      hours after extubation. CONCLUSION: In patients without neurological
      complications, CEA but not CAS was associated with a transient increase in the S
      100B serum levels. Results indicate that the increase in S-100B does not
      originate from extracerebral sources, but rather appears to represent an
      impairment of the blood-brain barrier integrity or subtle brain cell damage
      probably due to hypoperfusion during clamping. Sustained elevation of S-100B
      serum levels corresponded to the development of postoperative neurological
      deficits.

PMID- 16445323
TI  - Embolic protection filters for carotid stenting: differences in flow obstruction
      depending on filter construction.
AB  - PURPOSE: To investigate the pressure gradient and degree of flow reduction
      associated with embolus protection filters for carotid stenting in an in vitro
      experiment. METHODS: Three filter devices with a perforated membrane design and
      one wire mesh type filter were tested. At a pressure of 70 mmHg, the flow
      reduction and pressure gradient were measured in a 5-mm tube using blood
      mimicking fluid. RESULTS: The pressure gradient in the wire mesh filter was
      1.65+/-0.49 mmHg (95% CI 1.32 to 1.86). The mean pressure gradient in the
      perforated membrane filters was 6.88+/-2.62 mmHg (95% CI 6.22 to 7.55, p<0.0001).
      There was also a significant correlation between pressure gradient and flow
      reduction (r=-0.77, p<0.01). CONCLUSION: Embolic protection filters cause a
      pressure gradient and obstruct blood flow. This effect is marked in perforated
      membrane filters and almost absent in the wire mesh filter.

PMID- 16445324
TI  - Movement and dislocation of modular stent-grafts due to pulsatile flow and the
      pressure difference between the stent-graft and the aneurysm sac.
AB  - PURPOSE: To investigate the stability and movement of modular aortic stent-grafts
      subjected to oscillating forces from pulsatile blood flow, with particular
      reference to the thoracic aorta. METHODS: Analytical mathematical modeling was
      used to understand the forces on modular grafts. In a benchtop experiment, a
      transparent acrylic box was filled with water to mimic an aneurysm. Two stent
      grafts were placed inside the box in a nested, arched configuration where one
      component was partly inside the other. A pump produced a pulsatile approximately
      5-L/min flow of water through the stent-grafts at a mean inlet pressure of
      approximately 100 mmHg (approximately 13,330 Pa), with systolic and diastolic
      pressures of approximately 130 and approximately 80 mmHg, respectively (pulse
      pressure 50 mmHg). The movement of the 2 modular stent-grafts was observed.
      RESULTS: The curved stent-graft system oscillated transversely when there was
      zero mean pressure difference between the stent-graft and the aneurysm. As the
      mean pressure difference was increased, this transverse graft movement was damped
      and then disappeared. A relatively large pressure difference caused the stent
      graft to inflate and become sturdier. In terms of stability, the analytical
      mathematical model for a 30-mm-diameter Zenith modular stent-graft curved through
      90 degrees (with the ends of the graft fixed in place) showed that the modular
      components will separate at a pressure difference of 0 mmHg for 1 stent segment
      overlap (20 mm) and at an average 59 mmHg pressure difference for 2 stent
      overlaps, but the device would not separate at a pressure difference of 90 mmHg
      for 3 stent overlaps. CONCLUSION: Transverse cyclic movement of the curved stent
      graft system with pulsation indicates a pressurized sac. When the pressure
      difference is large and there is a blood-tight seal between the aneurysm and the
      stent-graft, then the transverse movement of the stent-graft is minimal, but the
      risk for modular separation is highest. Curved thoracic endografts are subject to
      forces that may cause migration or separation, the latter being more likely if
      the seal between the graft and the sac is blood tight, if the blood pressure is
      high, and if the diameter of the graft is small and the sac large. Operators
      should plan for maximum overlap of modular components when treating large or long
      thoracic aneurysms.

PMID- 16445326
TI  - A double-barrel stent-graft for endovascular repair of the aortic arch.
AB  - PURPOSE: To extend the role of endovascular aneurysm repair in the presence of
      angulation and dilatation of the distal arch that compromise the proximal
      implantation site. CASE REPORT: A 70-year-old man with an asymptomatic 7-cm
      thoracic aortic aneurysm was treated with a TAG stent-graft. However, attempts to
      gain secure hemostatic implantation of the endograft resulted in inadvertent
      coverage of the subclavian and left carotid arteries. Flow to the left carotid
      artery was re-established by transcarotid insertion of a self-expanding covered
      stent alongside the primary stent-graft. CONCLUSION: This technique may have a
      role as an intended part of endovascular repair when there is no suitable
      implantation site in the descending thoracic aorta.

PMID- 16445325
TI  - In vitro evaluation of current thoracic aortic stent-grafts for real-time MR
      guided placement.
AB  - PURPOSE: To systematically evaluate the magnetic resonance imaging (MRI)
      characteristics of current thoracic aortic stent-graft devices before, during,
      and after in vitro deployment as a step toward real-time MRI-guided stent
      placement. METHODS: Six stent-graft devices used for thoracic aortic repair were
      examined in a dedicated phantom model using a 1.5-T MRI scanner. First, the
      delivery systems with the mounted stent-graft were examined using real-time fast
      imaging with steady-state precession (TrueFISP) with Cartesian and radial k-space
      filling. TrueFISP imaging was subsequently used for real-time monitoring of stent
      graft expansion. The deployed stent-grafts were then examined in a water bath
      containing gadolinium (1:40) with high-resolution T1-weighted 3D fast low-angle
      shot (FLASH) sequences. The images were analyzed for artifacts, radiofrequency
      caging effects, and device visualization quality. RESULTS: Three delivery systems
      with mounted stent-grafts did not contain ferromagnetic elements and were well
      visualized. Imaging with radial k-space filling showed fewer artifacts than
      Cartesian imaging. Movement of the delivery system and stent-graft expansion of
      these devices were successfully demonstrated at a rate of up to 6 frames per
      second. Evaluation of the expanded stent-grafts revealed only minor
      susceptibility artifacts without relevant signal attenuation in the stent-graft
      lumen for 5 nitinol-based stent-grafts. Only a stainless steel-based stent-graft
      was associated with severe artifacts, thwarting visualization of its lumen or
      surroundings. CONCLUSION: The present study shows that 3 nitinol-based thoracic
      stent-graft devices are potentially suited for real-time MRI-guided placement
      with respect to both the delivery system and the stent-graft itself. These
      observations provide the basis for the evaluation of MRI-guided stent-graft
      placement in vivo.

PMID- 16445327
TI  - In vitro analysis of modular aortic stent-graft failure.
AB  - PURPOSE: To investigate the theoretical forces involved in and the nature of
      fixation between the modular components of a variety of aortic stent-grafts.
      METHODS: An in vitro study of 6 aortic stent-grafts was performed using a
      tensometer. The modular stent-graft components were distracted until the iliac
      limb was completely separated from the main body. Tests were repeated at least 6
      times for each stent-graft. RESULTS: The maximum pullout force was 36.0 N using
      the Fortron stent-graft, which resulted in stent-graft disintegration. The
      maximum median forces of the other stent-grafts were 23.7 N (19.9-31.2) for the
      Aorfix, 7.3 N (6.9-7.6) for the AneuRx, 7.0 N (6.8-7.1) for the Zenith BiFab, 5.4
      N (5.0-6.5) for the Talent, and 2.4 N (2.2-2.4) for the Vanguard II CONCLUSION:
      The results of this in vitro study suggest that current forms of iliac limb
      fixation in modular aortic stent-grafts are adequate provided the components are
      deployed with sufficient overlap. However, for many of the stent-grafts tested,
      the safety margin was small.

PMID- 16445328
TI  - Three-dimensional visualization of suprarenal aortic stent-grafts: evaluation of
      migration in midterm follow-up.
AB  - PURPOSE: To investigate the midterm results of transrenal fixation of abdominal
      aortic stent-grafts with regard to device migration and encroachment of stent
      wires on the renal and visceral branches. METHODS: Imaging data from 18 patients
      (15 men; mean age 75 years, range 63-84) undergoing transrenal stent-graft
      fixation for abdominal aortic aneurysm (AAA) were included in the study. Computed
      tomographic angiographic data acquired within 1 week of stent-graft implantation
      were compared to the latest follow-up images. Postprocessing methods generated 3
      dimensional (3D) maximum intensity projections (MIP) and virtual intravascular
      endoscopy (VIE) for evaluation of the relationship between suprarenal stents and
      aortic branches. Aortic neck angulation was measured in each patient for
      correlation with the incidence of stent migration. RESULTS: The mean follow-up
      period was 40 months. 3D image visualizations showed that the stent-graft moved
      caudally in all patients (range 2.6-14.2 mm), with migration (>10 mm) observed in
      4 (22%) patients. Corresponding VIE images documented changes in stent wire
      encroachment on the aortic branch ostia in 11 patients, including the number and
      position of crossing stent wires. There was no close relationship between aortic
      neck angulation and stent migration. CONCLUSION: The current study demonstrated
      that migration occurs at midterm follow-up in transrenally deployed stent-grafts.
      3D images were valuable for the assessment of stent migration, as well as its
      relationship with aortic branch ostia. Long-term follow-up of transrenal fixation
      deserves to be investigated, especially after observing stent migration relative
      to aortic ostial encroachment.

PMID- 16445329
TI  - Paradoxical effects of aurintricarboxylic acid and RG-13577: acute thrombosis and
      in-stent stenosis in a passive-coated stent.
AB  - PURPOSE: To investigate if a platelet inhibitor (aurintricarboxylic acid [ATA])
      and a heparin-mimicking antagonist (RG-13577) of basic fibroblast growth factor 2
      (bFGF2) could be combined as a stable compound and attached to conventional bare
      metal stents to hinder thrombus formation and inflammatory reactions of stenting.
      METHODS: Fifteen domestic pigs were stented with RG-13577/ATA-coated (n=6), ATA
      coated (n=12), and bare metal stents (n=12) in the left anterior descending (LAD)
      and left circumflex (LCX) coronary arteries. All surviving pigs were evaluated
      with contrast angiography and intravascular ultrasonography (IVUS) after 4 weeks.
      Histological analysis of the stented arteries was performed after hematoxylin
      eosin staining. Tissue factor (TF) staining and scanning electron microscopy
      (SEM) were performed in animals with acute stent thrombosis. RESULTS: Five of the
      6 animals receiving an RG-13577/ATA-coated stent experienced acute stent
      thrombosis, while no adverse events occurred in the animals of the other 2
      groups. Follow-up angiography did not show significant in-stent stenosis in
      either bare or ATA-coated stents. However, histomorphometry revealed larger
      neointimal area (3.54+/-0.69 mm2 versus 1.82+/-0.27 mm2, p<0.05) and outward
      plaque area (1.56+/-0.34 mm2 versus 0.61+/-0.12 mm2, p<0.05) in ATA-coated
      stents. Three-dimensional IVUS analysis showed analogous results, with
      significantly larger neointimal volume and outward plaque volume in ATA-coated
      stents. There was a slight increase in TF staining around the stent struts, while
      SEM showed increased platelet adhesion and activity in RG-13577/ATA-coated stents
      versus the ATA-coated and bare metal stents. CONCLUSION: RG-13577/ATA-coated
      stents lead to acute stent thrombosis. The ATA coating alone did not lead to
      acute events, but resulted in higher neointimal hyperplasia and expansive
      remodeling. These results underline the importance of preclinical studies before
      using new coated stents in human arteries.

PMID- 16445331
TI  - Effectiveness of continuous passive motion and conventional physical therapy
      after total knee arthroplasty: a randomized clinical trial.
AB  - BACKGROUND AND PURPOSE: This randomized clinical trial was conducted to compare
      the effectiveness of 3 in-hospital rehabilitation programs with and without
      continuous passive motion (CPM) for range of motion (ROM) in knee flexion and
      knee extension, functional ability, and length of stay after primary total knee
      arthroplasty (TKA). SUBJECTS: Eighty-one subjects who underwent TKA for a
      diagnosis of osteoarthritis were recruited. METHODS: All subjects were randomly
      assigned to 1 of 3 groups immediately after TKA: a control group, which received
      conventional physical therapy intervention only; experimental group 1, which
      received conventional physical therapy and 35 minutes of CPM applications daily;
      and experimental group 2, which received conventional physical therapy and 2
      hours of CPM applications daily. All subjects were evaluated once before TKA and
      at discharge. The primary outcome measure was active ROM in knee flexion at
      discharge. Active ROM in knee extension, Timed "Up & Go" Test results, Western
      Ontario and McMaster Universities Osteoarthritis Index questionnaire scores, and
      length of stay were the secondary outcome measures. RESULTS: The characteristics
      of and outcome measurements for the subjects in the 3 groups were similar at
      baseline. No significant difference among the 3 groups was demonstrated in
      primary or secondary outcomes at discharge. DISCUSSION AND CONCLUSION: The
      results of this study do not support the addition of CPM applications to
      conventional physical therapy in rehabilitation programs after primary TKA, as
      applied in this clinical trial, because they did not further reduce knee
      impairments or disability or reduce the length of the hospital stay.

PMID- 16445332
TI  - Effects of long-term gait training using visual cues in an individual with
      Parkinson disease.
AB  - BACKGROUND AND PURPOSE: In an attempt to improve the gait of people with
      Parkinson disease (PD), researchers have examined the effect of visual cues
      placed on the floor. These studies typically have used a single session of
      training with such cues and have not examined the long-term carryover of such
      training. In the present study, therefore, gait was analyzed during uncued, cued,
      and retention phases, each lasting 1 month. SUBJECT: A 78-year-old woman who had
      been diagnosed with PD 12 years previously (Hoehn and Yahr classification of
      disability, stage III) volunteered for the study. METHODS: During the initial
      uncued gait phase, the subject was required to walk a distance of 10 m as many
      times as she could in 30 minutes, 3 times per week for 4 weeks. During the 4-week
      cued gait phase, visual cues were placed on the floor along the 10-m walkway. The
      cues were initially 110% of the uncued step length and were later increased to
      120%. Following this cued gait phase, the subject's gait was recorded
      periodically for 1 month without cues available. Step length, gait speed, and 2
      dimensional lower-limb kinematics were compared within and across the 3
      experimental phases. Celeration lines were calculated for the initial uncued
      phase and then extrapolated across the cued training and uncued retention phases.
      Binomial tests were used to analyze the significance of changes from the initial
      phase of the experiment. RESULTS: Step length (0.53-0.56 m) and gait speed (0.77
      0.82 m x s(-1)) were essentially unchanged during uncued gait training after the
      first day; however, during the cued gait phase, gait speed improved, from 0.87 m
      x s(-1) to 1.13 m x s(-1), as step length was increased with visual cues.
      Improvements in step length (0.68 m) and gait speed (1.08 m x s(-1)) were still
      evident 1 month following the removal of the cues. Analyses of angle-angle
      diagrams and phase-plane portraits revealed that training with visual cues
      increased hip and knee range of motion and engendered more stable motor control
      of the lower limb. DISCUSSION AND CONCLUSION: In contrast to previous studies in
      which the benefits of visual cueing were relatively short-lived, in this study, 1
      month of gait training with visual cues was successful in establishing a lasting
      improvement in gait speed and step length while increasing the stability of the
      underlying motor control system.

PMID- 16445333
TI  - Developing a short form of the Berg Balance Scale for people with stroke.
AB  - BACKGROUND AND PURPOSE: To improve the utility of the Berg Balance Scale (BBS),
      the aim of this study was to develop a short form of the BBS (SFBBS) that was
      psychometrically similar (including test reliability, validity, and
      responsiveness) to the original BBS for people with stroke. SUBJECTS AND METHODS:
      A total of 226 subjects with stroke participated in this prospective study at 14
      days after their stroke; 167 of these subjects also were examined at 90 days
      after their stroke. The BBS, Barthel Index, and Fugl-Meyer Motor Test were
      administered at these 2 time points. By reducing the number of tested items by
      more than half the number of items in the original BBS (ie, making 4-, 5-, 6-,
      and 7-item tests) and simplifying the scoring system of the original BBS (ie,
      collapsing the 5-level scale into a 3-level scale [BBS-3P]), we generated a total
      of 8 SFBBSs. RESULTS: The distributions of scores for all 8 SFBBSs were
      acceptable but featured notable floor effects. The 4-item BBS, 5-item BBS, 5-item
      BBS-3P, and 7-item BBS-3P demonstrated good reliability. The subjects' scores on
      the 6-item BBS, 6-item BBS-3P, 7-item BBS, and 7-item BBS-3P showed excellent
      agreement with those on the original BBS. The 6-item BBS-3P and 7-item BBS-3P
      exhibited great responsiveness. Only the 7-item BBS-3P demonstrated both
      satisfactory and psychometric properties similar to those of the original BBS.
      DISCUSSION AND CONCLUSION: The 7-item BBS-3P was found to be psychometrically
      similar to the original BBS. The 7-item BBS-3P, compared with the original BBS,
      is simpler and faster to complete in either a clinical or a research setting and
      is recommended.

PMID- 16445334
TI  - Reliability and validity of arm volume measurements for assessment of lymphedema.
AB  - BACKGROUND AND PURPOSE: Arm lymphedema following breast cancer surgery is a
      continuing problem. In this study, we assessed the reliability and validity of
      circumferential measurements and water displacement for measuring upper-limb
      volume. SUBJECTS: Participants included subjects who had had breast cancer
      surgery, including axillary dissection--19 with and 22 without a diagnosis of arm
      lymphedema--and 25 control subjects. METHODS: Two raters measured each subject by
      using circumferential tape measurements at specified distances from the
      fingertips and in relation to anatomic landmarks and by using water displacement.
      Interrater reliability was calculated by analysis of variance and multilevel
      modeling. Volumes from circumferential measurements were compared with those from
      water displacement by use of means and correlation coefficients, respectively.
      The standard error of measurement, minimum detectable change (MDC), and limits of
      agreement (LOA) for volumes also were calculated. RESULTS: Arm volumes obtained
      with these methods had high reliability. Compared with volumes from water
      displacement, volumes from circumferential measurements had high validity,
      although these volumes were slightly larger. Expected differences between
      subjects with and without clinical lymphedema following breast cancer were found.
      The MDC of volumes or the error associated with a single measure for data based
      on anatomic landmarks was lower than that based on distance from fingertips. The
      mean LOA with water displacement were lower for data based on anatomic landmarks
      than for data based on distance from fingertips. DISCUSSION AND CONCLUSION:
      Volumes calculated from anatomic landmarks are reliable, valid, and more accurate
      than those obtained from circumferential measurements based on distance from
      fingertips.

PMID- 16445335
TI  - Characteristics of foot movement in Tai Chi exercise.
AB  - BACKGROUND AND PURPOSE: The concept of proper foot movement is always emphasized
      in practicing Tai Chi (TC). The purposes of this study were to describe the foot
      movement characteristics of TC and to compare duration of single- and double-limb
      support time during TC and during walking. SUBJECTS: Sixteen experienced TC
      practitioners participated in the study. METHODS: The participants' performance
      of a whole set of 42-form TC movements was recorded with 2 cameras. A motion
      analysis system was used to identify the supporting and stepping characteristics
      of the foot during the practice. RESULTS: Seven foot support patterns and 6 step
      directions were identified. The results revealed that, compared with normal
      walking, TC movement had more double-limb support and less single-limb support in
      terms of total duration. The duration of each support pattern was longer, and
      movement from one pattern to the next was slow. The duration of each step
      direction was short, and changes of direction were frequent. DISCUSSION AND
      CONCLUSION: Support patterns changed slowly, and, combined with various step
      directions, they were found to be better than those of walking in simulating the
      gait challenges that may be encountered in daily activities.

PMID- 16445336
TI  - A faculty's experience in changing instructional methods in a professional
      physical therapist education program.
AB  - BACKGROUND AND PURPOSE: In response to the demands of a changing practice
      environment, many physical therapist educators have incorporated problem-based
      learning methods into their teaching. The purpose of this study was to describe a
      physical therapist program faculty's experience in transitioning from traditional
      instruction to problem-based instructional methods. SUBJECTS AND METHODS: Face-to
      face, semistructured interviews followed by a focus group were conducted with 7
      faculty members, guided by questions about factors that influenced instructors'
      experience of changing instructional methods. RESULTS: Nine themes described the
      faculty's experience: perception of need for teaching change, personal knowledge
      of problem-based learning, decision-making process, peer support, partial
      adoption, values related to teaching and learning, significant response from the
      community, administrative support, and perceived barriers to incorporation of
      problem-based methods. DISCUSSION AND CONCLUSION: The findings are consistent
      with literature describing change: change is a process, the process of change
      must accommodate individual change, a network of peer support is necessary, and
      the change process requires leadership and support from administrators within and
      outside of the group.

PMID- 16445337
TI  - Effects of repetitive shortwave diathermy for reducing synovitis in patients with
      knee osteoarthritis: an ultrasonographic study.
AB  - BACKGROUND AND PURPOSE: Shortwave (SW) diathermy can be used to improve vascular
      circulation and reduce inflammation and pain for patients with osteoarthritis.
      However, reduction in synovial inflammation has never been explored. The purpose
      of this study was to investigate whether repetitive SW diathermy, using
      ultrasonographic examination, could reduce synovitis in patients with knee
      osteoarthritis. SUBJECTS AND METHODS: Thirty subjects with 44 osteoarthritic
      knees participated in this study. Eleven subjects received SW, and 10 subjects
      received SW and nonsteroidal anti-inflammatory drugs. Nine subjects received no
      treatment and served as a control group. Synovial sac thickness superior, medial,
      and lateral to the patella was measured using ultrasonography. The sum of these 3
      measurements was taken as the total synovial sac thickness. Subjects in the
      treatment groups underwent ultrasonographic examination before and after 10, 20,
      and 30 treatments, whereas control subjects underwent ultrasonographic
      examination before the experiment and then once every 2 or 3 weeks for a total of
      3 follow-up measurements. RESULTS: After 10 SW diathermy treatments, the total
      synovial sac thickness in both treatment groups was significantly less than the
      initial thickness, and the synovial sac continued to become significantly thinner
      with 20 sessions of treatment. These observations were not made in the control
      subjects. DISCUSSION AND CONCLUSION: The results indicate that SW diathermy in
      patients with knee osteoarthritis can significantly reduce both synovial
      thickness and knee pain. Such reductions of synovial sac thickness and pain index
      continue over treatment sessions.

PMID- 16445338
TI  - Comparing 2 versions of the Chedoke Arm and Hand Activity Inventory with the
      Action Research Arm Test.
AB  - BACKGROUND AND PURPOSE: The Chedoke Arm and Hand Activity Inventory (CAHAI) is a
      new, validated upper-limb measure that uses a 7-point quantitative scale in order
      to assess functional recovery of the arm and hand after a stroke. The purposes of
      this study were: (1) to determine whether the longitudinal validity of scores on
      2 versions of a new upper-limb measure, the CAHAI (CAHAI-9 and CAHAI-13), was
      greater than that of scores on the Action Research Arm Test (ARAT) and (2) to
      determine whether the cross-sectional and longitudinal validity of the CAHAI-13
      scores was greater than that of the CAHAI-9 scores. SUBJECTS: One hundred five
      people with upper-limb dysfunction following a stroke were stratified into 2
      impairment groups (mild to moderate and severe), which were expected to change by
      different amounts. METHODS: The CAHAI-13 and ARAT were administered twice (time
      between assessments varied from 2 to 6 weeks). Receiver operating characteristic
      curves, Pearson product moment coefficient of correlation, and regression
      analyses were used. RESULTS: Receiver operating characteristic curve areas (CAHAI
      13=0.86, CAHAI-9=0.82, ARAT=0.72) were significantly greater for the CAHAI
      versions. Scores on both CAHAI versions had identical levels of cross-sectional
      validity. DISCUSSION AND CONCLUSION: Both CAHAI versions demonstrated more
      sensitivity to change than the ARAT. It remains unclear whether the CAHAI-9
      provides precise estimates of CAHAI-13 scores at the individual level.

PMID- 16445339
TI  - Differential diagnosis and treatment in a patient with posterior upper thoracic
      pain.
AB  - BACKGROUND AND PURPOSE: Determining the source of a patient's pain in the upper
      thoracic region can be difficult. Costovertebral (CV) and costotransverse (CT)
      joint hypomobility and active trigger points (TrPs) are possible sources of upper
      thoracic pain. This case report describes the clinical decision-making process
      for a patient with posterior upper thoracic pain. CASE DESCRIPTION: The patient
      had a 4-month history of pain; limited cervical, trunk, and shoulder active range
      of motion; limited and painful mobility of the right CV/CT joints of ribs 3
      through 6; and periscapular TrPs. Interventions included CV/CT joint
      mobilizations, TrP release, and flexibility and postural exercises. OUTCOMES: The
      patient reported intermittent mild discomfort after 7 physical therapy sessions.
      Examination findings were normal, and he was able to resume all preinjury
      activities. DISCUSSION: This case suggests that CV/CT mobilizations and active
      TrP release may have been beneficial in reducing pain and restoring function in
      this patient.

PMID- 16445340
TI  - Training of balance under single- and dual-task conditions in older adults with
      balance impairment.
AB  - BACKGROUND AND PURPOSE: Traditionally, rehabilitation programs emphasize training
      balance under single-task conditions to improve balance and reduce risk for
      falls. The purpose of this case report is to describe 3 balance training
      approaches in older adults with impaired balance. CASE DESCRIPTIONS: Three
      patients were randomly assigned to 1 of 3 interventions: (1) single-task balance
      training, (2) dual-task training under a fixed-priority instructional set, and
      (3) dual-task training under a variable-priority instructional set. OUTCOMES: The
      patients who received balance training under dual-task conditions showed dual
      task training benefits; these training benefits were maintained for 3 months. The
      patient who received variable-priority training showed improvement on novel dual
      tasks. DISCUSSION: Older adults may be able to improve their balance under dual
      task conditions only following specific types of balance training. This case
      report gives insight on how this intervention might be combined with more
      traditional physical therapy intervention.

PMID- 16445341
TI  - Prologue to "Rehabilitation Medicine Summit: Building Research Capacity-
      executive summary".

PMID- 16445344
TI  - The Proteomics Identifications Database (PRIDE) and the ProteomExchange
      Consortium: making proteomics data accessible.

PMID- 16445342
TI  - Rehabilitation Medicine Summit: Building Research Capacity--executive summary.
AB  - The general objective of the Rehabilitation Medicine Summit: Building Research
      Capacity was to advance and promote research in medical rehabilitation by making
      recommendations to expand research capacity. The 5 elements of research capacity
      that guided the discussions were: (1) researchers, (2) research environment,
      infrastructure, and culture, (3) funding, (4) partnerships, and (5) metrics. The
      [approximately] 100 participants included representatives of professional
      organizations, consumer groups, academic departments, researchers, governmental
      funding agencies, and the private sector. The small-group discussions and plenary
      sessions generated an array of problems, possible solutions, and recommended
      actions. A post-Summit, multi-organizational initiative is called to pursue the
      agendas outlined in this report.

PMID- 16445346
TI  - Proteome Society meeting. October 19, 2005, MA, USA.

PMID- 16445347
TI  - Electrophoresis in 2005: 22nd Annual Meeting of the American Electrophoresis
      Society. October 30-November 4, 2005, OH, USA.

PMID- 16445348
TI  - Role of proteomics in translational research in cervical cancer.
AB  - Cervical cancer is one of the leading causes of cancer morbidity and mortality in
      women worldwide. More than 98% of cases are related to a human papillomavirus
      (HPV) infection. Infection with specific subtypes of HPV has been strongly
      implicated in cervical carcinogenesis. The identification and functional
      verification of host proteins associated with HPV E6 and E7 oncoproteins may
      provide useful information for understanding cervical carcinogenesis and the
      development of cervical cancer-specific markers. In addition, proteomic profiling
      of altered proteins by anticancer drugs on cervical cancer cells may contribute
      to providing the fundamental resources for investigation of disease-specific
      target proteins, elucidation of the novel mechanisms of action and development of
      new drugs. The advent of proteomics has provided the hope of discovering novel
      biological markers for use in the screening, early diagnosis and prediction of
      response to therapy. This review describes the studies where profiles of protein
      expression in cervical cancer have been generated.

PMID- 16445349
TI  - ELISA microarray technology as a high-throughput system for cancer biomarker
      validation.
AB  - A large gap currently exists between the ability to discover potential biomarkers
      and the ability to assess the real value of these proteins for cancer screening.
      One major challenge in biomarker validation is the inherent variability in
      biomarker levels. This variability stems from the diversity across the human
      population and the considerable molecular heterogeneity between individual
      tumors, even those that originate from a single tissue. An additional challenge
      with cancer screening is that most cancers are rare in the general population,
      meaning that assay specificity must be very high. Otherwise, the number of false
      positives will be much greater than the number of true positives. Due to these
      challenges associated with biomarker validation, it is necessary to analyze
      thousands of samples in order to obtain a clear idea of the utility of a
      screening assay. Enzyme-linked immunosorbent assay (ELISA) microarray technology
      can simultaneously quantify levels of multiple proteins and, thus, has the
      potential to accelerate validation of protein biomarkers for clinical use. This
      review will discuss current ELISA microarray technology and potential advances
      that could help to achieve the reproducibility and throughput that are required
      to evaluate cancer biomarkers.

PMID- 16445350
TI  - 2D gel blood serum biomarkers reveal differential clinical proteomics of the
      neurodegenerative diseases.
AB  - This review addresses the challenges of neuroproteomics and recent progress in
      biomarkers and tests for neurodegenerative diseases, including Alzheimer's
      disease, Parkinson's disease and amyotrophic lateral sclerosis. The review will
      discuss how the application of quantitative 2D gel electrophoresis, combined with
      appropriate single-variable and multivariate biostatistics, allows for selection
      of disease-specific serum biomarkers. It will also address how the use of large
      cohorts of specifically targeted patient blood serum samples and complimentary
      age-matched controls, in parallel with the use of selected panels of these
      biomarkers, are being applied to the development of blood tests to specifically
      address unmet pressing needs in the differential diagnosis of these diseases, and
      to provide potential avenues for mechanism-based drug targeting and treatment
      monitoring. While exploring recent findings in this area, the review discusses
      differences in critical pathways of immune/inflammation and amyloid formation
      between Parkinson's disease and amyotrophic lateral sclerosis, as well as
      discernable synergistic relationships between these pathways that are revealed by
      this approach. The potential for pathway measurement in blood tests for
      differential diagnosis, disease burden and therapeutic monitoring is also
      outlined.

PMID- 16445351
TI  - Discovery of regulatory molecular events and biomarkers using 2D capillary
      chromatography and mass spectrometry.
AB  - An important component of proteomic research is the high-throughput discovery of
      novel proteins and protein-protein interactions that control molecular events
      that contribute to critical cellular functions and human disease. The
      interactions of proteins are essential for cellular functions. Identifying
      perturbation of normal cellular protein interactions is vital for understanding
      the disease process and intervening to control the disease. A second area of
      proteomics research is the discovery of proteins that will serve as biomarkers
      for the early detection, diagnosis and drug treatment response for specific
      diseases. These studies have been referred to as clinical proteomics. To discover
      biomarkers, proteomics research employs the quantitative comparison of peptide
      and protein expression in body fluids and tissues from diseased individuals
      (case) versus normal individuals (control). Methods that couple 2D capillary
      liquid chromatography (LC) and tandem mass spectrometry (MS/MS) analysis have
      greatly facilitated this discovery science. Coupling 2D-LC/MS/MS analysis with
      automated genome-assisted spectra interpretation allows a direct, high-throughput
      and high-sensitivity identification of thousands of individual proteins from
      complex biological samples. The systematic comparison of experimental conditions
      and controls allows protein function or disease states to be modeled. This review
      discusses the different purification and quantification strategies that have been
      developed and used in combination with 2D-LC/MS/MS and computational analysis to
      examine regulatory protein networks and clinical samples.

PMID- 16445352
TI  - Delineating signal transduction pathways in smooth muscle through focused
      proteomics.
AB  - This review will outline examples of the authors' focused proteomics approaches
      to studying signal transduction pathways in smooth muscle. By focusing the use of
      traditional proteomics techniques with hypothesis-driven selection methods, this
      approach efficiently addresses the identification of novel elements in a signal
      transduction pathway of interest. However, focused proteomics serves only as a
      starting point in the investigation of novel signaling proteins. While focused
      proteomics studies can suggest the involvement and general biochemical function
      of a protein in a signaling pathway, these findings must be further investigated
      and validated. Through the integrated use of focused proteomics with
      complementary approaches such as genetics, biochemistry and cell physiology, a
      complete and detailed mechanism of signal transduction can be determined.

PMID- 16445354
TI  - Protein turnover on the scale of the proteome.
AB  - Protein turnover is a neglected dimension in postgenomic studies, defining the
      dynamics of changes in protein expression and forging a link between
      transcriptome, proteome and metabolome. Recent advances in postgenomic
      technologies have led to the development of new proteomic techniques to measure
      protein turnover on a proteome-wide scale. These methods are driven by stable
      isotope metabolic labeling of cells in culture or in intact animals. This review
      considers the merits and difficulties of different methods that allow access to
      proteome dynamics.

PMID- 16445353
TI  - Proteomics of the human malaria parasite Plasmodium falciparum.
AB  - The lethal species of malaria parasite, Plasmodium falciparum, continues to exact
      a huge toll of mortality and morbidity, particularly in sub-Saharan Africa.
      Completion of the genome sequence of this organism and advances in proteomics and
      mass spectrometry have opened up unprecedented opportunities for understanding
      the complex biology of this parasite and how it responds to drug challenge and
      other interventions. This review describes recent progress that has been made in
      applying proteomics technology to this important pathogen and provides a look
      forward to likely future developments.

PMID- 16445355
TI  - Protein chips for high-throughput doping screening in athletes.
AB  - Sport and doping are a contradiction in terms, however, doping abuse in sports
      has been a serious problem for many years. The systematic screening of every
      athlete for all prohibited drugs should be an indispensable feature of the
      Olympic Games. The gas chromatography mass spectrometry method is reserved as a
      reference method, but is limited by its low throughput. The advent of protein
      chip technology may enable the screening of all athletes for any illegal use of
      drugs.

PMID- 16445356
TI  - Highbrow proteasome in high-throughput technology.
AB  - Proteasome is a major protease of the ubiquitin-proteasome pathway involved in
      the regulation of practically all intracellular biochemical processes. The enzyme
      core is created by a heteromultimer of complex architecture built with multiple
      subunits arranged into a tube-like structure. The multiple active sites of
      diverse peptidase specificity are hidden inside the tube. Access to the interior
      is guarded by a gate formed by the N-termini of specialized subunits and by the
      attachment of additional multisubunit protein complexes controlling the enzymatic
      capabilities of the core. Proteasome, due to its Byzantine molecular architecture
      and equally sophisticated enzymatic mechanism, is by itself a fascinating
      biophysical object. Recently, the position of the protease advanced from an
      academically remarkable protein processor to a providential anticancer drug
      target and futuristic nanomachine. Proteomics studies actively shape our current
      understanding of the protease and direct the future applications of the
      proteasome in medicine.

PMID- 16445357
TI  - Effects of post-electrophoretic analysis on variance in gel-based proteomics.
AB  - 2D electrophoresis (2DE) is a prominent separation method for complex proteomes.
      Although recent advances have increased the utility of this method in
      quantitative proteomics studies, many sources of variance still exist. This
      review discusses the post-electrophoretic sources of variance in current 2DE
      analysis. The essential improvements in protein visualization and software
      algorithms that have made 2DE a leading quantitative proteomics method are
      briefly reviewed. A number of shortcomings in the post-electrophoretic analysis
      of 2DE data that require further attention are highlighted. Topics discussed
      include protein visualization and image acquisition, internal standards and
      normalization methods, background subtraction algorithms, normality of
      distribution, and the need for standardized tests for the evaluation of 2DE
      analysis software packages.

PMID- 16445358
TI  - Recent developments in ion-trap mass spectrometry and related technologies.
AB  - Due to their versatility, quadrupole ion traps have become popular mass
      spectrometers in the growing field of proteomics. High sensitivity, user
      friendliness and low cost are the key features that have contributed to the
      success of the technology. However, mass measurement accuracy, resolution and
      mass range are still not comparable to the analytical performances obtained on
      other mass spectrometers. In the past 5 years, researchers have tried to overcome
      these drawbacks, focusing their attention on two different aspects of ion-trap
      mass spectrometry, development of novel types of ion traps and manipulation of
      the gas-phase ion chemistry, in order to obtain alternative techniques for tandem
      mass spectrometry analysis. In the field of trapping devices, improvements in
      instrumental design have led to the linear ion trap, digital ion trap and
      orbitrap. Activation methods based on electrons, chemically produced by an anion
      or from irradiation with an electron beam, have demonstrated their utility in
      providing complementary sequence information for improving confidence in protein
      identification.

PMID- 16445359
TI  - Surface-assisted laser desorption/ionization mass spectrometry.
AB  - Laser desorption/ionization mass spectrometry (MS) is rapidly growing in
      popularity as an analytical characterization method in several fields. The
      technique shot to prominence using matrix-assisted desorption/ionization for
      large biomolecules (>700 Da), such as proteins, peptides and nucleic acids.
      However, because the matrix, which consists of small organic molecules, is also
      ionized, the technique is of limited use in the low-molecular-mass range (<700
      Da). Recent advances in surface science have facilitated the development of
      matrix-free laser desorption/ionization MS approaches, which are referred to here
      as surface-assisted laser desorption/ionization (SALDI) MS. In contrast to
      traditional matrix-assisted techniques, the materials used for SALDI-MS are not
      ionized, which expands the usefulness of this technique to small-molecule
      analyses. This review discusses the current status of SALDI-MS as a standard
      analytical technique, with an emphasis on potential applications in proteomics.

PMID- 16445360
TI  - Attentional demands and daily functioning among community-dwelling elders.
AB  - Everyday life is full of numerous demands for attention that can affect the
      ability to function. For elders, examples of these attentional demands include
      negotiating public transportation and driving, sensory losses, and physical
      discomforts and worries that make it harder to concentrate and complete tasks.
      The purpose of this study was to examine the relation between attentional demands
      and the ability to manage daily activities requiring concentration for 54
      community-dwelling elders (34 women, 20 men). As theorized, attentional demands
      correlated (r = -.58) significantly with daily functioning: Elders with more
      attentional demands perceived themselves as having greater difficulty managing
      tasks requiring concentration. Attentional demands accounted for a significant
      proportion of variance in functioning (12%), even after partialling out the
      effects of depressive symptoms and health. Findings support the theorized
      relation between attentional demands and daily functioning, as well as nursing
      interventions aimed at decreasing attentional demands to promote effective
      functioning for elders.

PMID- 16445361
TI  - A comparison of pharmacological tobacco cessation relapse rates.
AB  - Tobacco use is the nation's leading preventable cause of chronic illness and
      injury; it takes the lives of 450,000 of our citizens each year. Currently, there
      are numerous treatment programs and pharmacological aids that may be obtained
      with a prescription or purchased over the counter at your local drugstore. The
      purpose of this study was to compare differences in tobacco cessation relapse
      rates of military personnel at the 1-, 3-, and 6-month intervals among 4
      categories of pharmacological and cognitive regimens used at an outpatient naval
      treatment facility. A nonprobability convenience sampling plan was used to obtain
      (a) 10 patient-participant Freedom From Smoking (FFS) course records that
      utilized Zyban and Nicotine Replacement Therapy, (b) 10 patient-participant FFS
      course records that utilized Zyban only, (c) 10 patient-participant FFS course
      records that utilized Nicotine Replacement Therapy only, and (d) 10 patient
      participant FFS course records that utilized Nicotine Replacement Therapy and
      nicotine gum (as needed). Findings revealed no significant difference between
      relapse and associated pharmacological treatment program. There was, however, a
      moderate increased cessation effort in Program 4 (nicotine replacement patch and
      nicotine gum). Results also demonstrated no significant difference between
      demographic variables and relapse cohorts. A significant positive relation
      between length of smoking and packs smoked per day was revealed, however.

PMID- 16445362
TI  - A computer-assisted instructional program for teaching portion size versus
      serving size.
AB  - Obesity is becoming an increasingly important community health threat, accounting
      for more than 300,000 deaths per year in the United States. The cumulative
      economic impact of obesity and overeating is enormous. Factors contributing to
      the problem include eating food away from home, consuming large or excessive
      quantities of soft drinks and snack foods, and large portion sizes.
      Discriminating between portion and serving sizes and determining the appropriate
      number of serving sizes to consume on a daily basis are key to maintaining a
      healthy diet. The purpose of this project was to create a computer-assisted
      instructional tool delineating serving size from portion size. The tool can be
      used by health care professionals to provide direct instruction to individuals or
      as part of a group approach to healthy eating.

PMID- 16445363
TI  - Screening for depression among pregnant and postpartum women.
AB  - The purpose of this study was to examine the screening of depression among
      pregnant and postpartum participants in a community-based program. This cross
      sectional study used archival data from 98 women participating in a community
      based visiting nurse program in a midwestern U.S. city. Depression screening was
      accomplished using the Center for Epidemiologic Studies Depression scale (CES-D)
      and Edinburgh Postnatal Depression scale (EPDS); both instruments ask respondents
      to answer questions regarding their mood during the past week. The CES-D
      identified more pregnant and postpartum women as depressed than did the EPDS. A
      standard regression analysis using previous pregnancies, history of depression,
      married versus nonmarried, presence of support, and breast-feeding as predictor
      variables did not produce statistically significant findings for predicting
      depression among the pregnant and postpartum women in this study. This finding
      underscores the value of brief depression screening instruments for nurses
      working with pregnant and postpartum women.

PMID- 16445364
TI  - Living with diabetes: perceptions of Hispanic migrant farmworkers.
AB  - This study1 focuses on Hispanic migrant farmworkers and their perceptions of
      living with diabetes. A phenomenological design was utilized with a sample of 12
      participants recruited from 2 local migrant health centers. The interview guide
      was based on questions from Kleinman's Explanatory Model. Data were explored with
      regard to etiology, onset of symptoms, pathophysiology, and course of illness.
      Six themes emerged from the analysis: usualness of diabetes, causes of diabetes,
      symptoms prior to the diagnosis of diabetes, understanding the chronicity of
      diabetes, impact of diabetes on daily life, and fear of long-term complications
      related to diabetes. Based on the analysis of the interviews, the individuals'
      explanations of this chronic disease are compiled within their own perceptions
      and cultural beliefs. The results of this study can be utilized by providers to
      adapt their health care and education methods to better meet the needs of this
      mobile population. In the Hispanic migrant farmworker population, further
      research is needed to explore the long-term impact of living with diabetes on a
      daily basis.

PMID- 16445367
TI  - Integrating novel agents into the curative treatment of head and neck cancer.

PMID- 16445369
TI  - Gemcitabine and carboplatin: is this the best combination for non-small cell lung
      cancer?
AB  - Approximately 30-40% of non-small cell lung cancer patients will present with
      metastatic disease, and its associated poor prognosis. Chemotherapy has an
      established palliative role within late-stage disease, but is also being used
      increasingly in the neoadjuvant and adjuvant settings. Platinum-based
      chemotherapy has been shown to produce definite improvements in efficacy and
      quality of life in non-small cell lung cancer patients, and is now the standard
      of care. Carboplatin has similar biochemical properties to those of cisplatin.
      However, carboplatin has much less renal, otologic, neurologic and upper
      gastrointestinal toxicities than cisplatin, and treatment can be conveniently
      delivered in an out-patient setting. Furthermore, platinum combinations with
      third-generation cytotoxics have shown additional gains in survival rates.
      Gemcitabine and carboplatin is a well-tolerated regime. Recent meta- and cost
      analyses have discovered that gemcitabine-based regimes may have an advantage
      over other third-generation agent platinum combinations. This article reviews the
      evidence demonstrating that gemcitabine-carboplatin is effective, convenient and
      cost effective.

PMID- 16445371
TI  - BRCA1-associated complexes: new targets to overcome breast cancer radiation
      resistance.
AB  - Since BRCA1 was cloned a decade ago, significant progress has been made in
      defining its biochemical and biological functions, as well as its role in breast
      and ovarian cancers. BRCA1 has been implicated in many cellular processes,
      including DNA repair, cell cycle checkpoint control, protein ubiquitination and
      chromatin remodeling. This review examines the role(s) of BRCA1 in mediating
      these cellular processes, and discusses its potential involvement in the
      resistance of breast cancer to radiation-based therapies. Finally, the
      possibility that BRCA1-associated proteins may serve as new targets for breast
      cancer radiation therapy is explored. The activation or inactivation of these
      BRCA1-associated proteins may modify both the risk of developing cancers in BRCA1
      mutation carriers and the efficacy of breast cancer therapy, including radiation.

PMID- 16445370
TI  - Protein kinase Calpha and epsilon small-molecule targeted therapeutics: a new
      roadmap to two Holy Grails in drug discovery?
AB  - Protein kinase (PK)Calpha and epsilon are rational targets for cancer therapy.
      However, targeted experimental therapeutics that inhibit PKCalpha or epsilon are
      unavailable. The authors established recently that covalent modification of an
      active-site cysteine in human PKCepsilon, Cys452, by small molecules, for example
      2-mercaptoethanolamine, is necessary and sufficient to render PKCepsilon kinase
      dead. Cys452 is conserved in only eleven human protein kinase genes, including
      PKCalpha. Therefore, the design of small molecules that bind PKC active sites
      with an electrophile substituent positioned proximal to the Cys452 side chain may
      lead to targeted therapeutics that selectively inhibit PKCepsilon, PKCalpha or
      other PKC isozymes.

PMID- 16445372
TI  - Cost-effective treatment options in first-line therapy for advanced breast cancer
      in Japan.
AB  - Concern regarding the economic aspect of cancer care has been increasing in the
      face of mounting healthcare expenditure in Japan. The need, not only for
      effective, but also for efficient treatment options in breast cancer care have
      been recognized in a broader context. In clinical practice, treatment options in
      first-line therapy for advanced breast cancer have become similar to those in
      Western countries in the past 5 to 10 years in the context of so-called 'evidence
      based medicine' employing clinical evidence; whereas evidence of cost
      effectiveness has been less acknowledged. Limited economic evidence suggests that
      current Japanese practice in first-line hormonal therapy is cost-effective.
      However, the efficiency of other options, such as chemotherapy, remains unknown.
      The expanding use of an expensive molecular-targeting agent, trastuzumab, has
      great implications for a treatment algorithm for breast cancer as well as for
      cost-effectiveness of care. Trastuzumab, of which use in first-line therapy was
      not found to be cost-effective in Western countries, is expected to be used for a
      number of HER2-overexpressing primary breast cancers in Japan. The extension of
      indication of this single agent would increase national healthcare expenditure by
      0.1%. The authors believe explicit discussion on value for money of new expensive
      drugs would be unavoidable, not only among health policy makers, but also leading
      breast cancer specialists in Japan in the near future.

PMID- 16445373
TI  - Optimizing locoregional control and survival for women with breast cancer: a
      review of current developments in postmastectomy radiotherapy.
AB  - For women who opt for mastectomy as primary surgery in breast cancer, indications
      for adjuvant radiotherapy are also being redefined in light of evidence
      demonstrating that postmastectomy radiotherapy (PMRT), when given in conjunction
      with systemic therapy, improves, not only locoregional control, but also
      survival. However, in certain settings, particularly in patients wih intermediate
      risk disease, and in some patients treated with neoadjuvant chemotherapy, the
      role of PMRT remains controversial. Here, the authors review modern data
      pertaining to the benefits and risks of PMRT and discuss controversies related to
      the indications for PMRT, focusing on patients with T1-2 breast cancer with 0-3
      positive nodes and patients treated with neoadjuvant chemotherapy. They also
      summarize key issues related to the integration of PMRT with other treatment
      modalities.

PMID- 16445374
TI  - MYCN deregulation as a potential target for novel therapies in rhabdomyosarcoma.
AB  - Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Treatment
      requires a multimodality approach combining chemotherapy with surgery and
      radiotherapy. Although overall outcomes have improved considerably, the outlook
      for patients with high-risk disease, particularly the alveolar subtype, remains
      bleak and there is a clear need for new chemotherapeutic strategies. This review
      focuses on the possibilities for interventions targeting myc myelocytomatosis
      viral related oncogene, neuroblastoma derived (MYCN). The importance of aberrant
      expression of this oncogene is well established in neuroblastoma and recent data
      indicate that MYCN deregulation also occurs in up to a quarter of alveolar
      subtype cases. A range of possible approaches to target MYCN is discussed,
      including nucleic acid-based and immunotherapy strategies.

PMID- 16445375
TI  - The role of high-dose therapy and autologous stem cell transplantation for
      pediatric bone and soft tissue sarcomas.
AB  - The prognosis for children with bone and soft tissue sarcomas has significantly
      improved since the advent of effective multiagent chemotherapy, aggressive
      surgery for local disease and more precise delivery of radiotherapy doses.
      However, in a small proportion of patients that present with high-risk disease,
      long-term outcome has not substantially increased, with disease-free survival
      rates still in the order of 20-30%. It is therefore clear that novel therapies
      are needed for children with these tumors. Based on the highly chemosensitive
      nature of the majority of pediatric sarcomas, several small studies have been
      conducted to investigate the potential role of high-dose chemotherapy followed by
      hematopoietic stem cell reconstitution. This review will provide an overview of
      the current literature concerning the use of high-dose therapy with stem cell
      transplantation for the three main pediatric sarcomas--Ewing sarcoma,
      rhabdomyosarcoma and osteosarcoma.

PMID- 16445376
TI  - Surgical options and outcomes in bone sarcoma.
AB  - Bone sarcomas are challenging to treat. The primary goal of treatment is local
      control of the disease while, if possible, achieving salvage of the limb and its
      function. There is no ideal method of reconstruction in limb-salvage surgery but
      the choice of the method of reconstruction should be individualized based upon
      many factors including the patient's age, the extent and location of the tumor,
      the wishes of the patient, and the availability of surgical facilities and
      expertise, as well as the cost of the procedure. In this review, the authors
      explore the advantages and disadvantages of the different methods of limb
      reconstruction. The surgical management of bone sarcomas is a real challenge to
      the orthopedic surgeon, owing to the diversity of sites in which tumors arise,
      combined with the extension of the tumor into adjacent soft tissues and their
      proximity, in many cases, to major neurovascular structures. There have been
      dramatic improvements in survival for patients with osteosarcoma and Ewing's
      sarcoma in the past 30 years owing to increasing effectiveness of chemotherapy.
      This, along with developments in imaging techniques (magnetic resonance imaging
      in particular) has led to earlier diagnosis and more accurate preoperative
      staging. Whilst traditional treatment for bone tumors used to be amputation,
      advances in surgical techniques have made limb-salvage procedures a valid
      alternative method of treatment to amputation in 80-85% of patients with primary
      bone sarcomas.

PMID- 16445377
TI  - Wilms' tumor: past, present and (possibly) future.
AB  - Wilms' tumor is one of the successes of pediatric oncology, with an overall cure
      rate of over 85%, using relatively simple therapies. This excellent outcome has
      been the result of collaborative efforts among surgeons, pediatricians,
      pathologists and radiation oncologists. The results that have been achieved in
      children with Wilms' tumors support the strong value of the multidisciplinary
      team approach to cancer. The two largest cooperative groups that have studied the
      optimum treatment for Wilms' tumor are the National Wilms' Tumor Study group in
      North America and the International Society of Pediatric Oncology, involving
      European and other countries. The National Wilms' Tumor Study group recommends
      primary surgery before any adjuvant treatment, whereas the International Society
      of Pediatric Oncology trials are based on the use of preoperative chemotherapy.
      The debate on primary chemotherapy versus primary nephrectomy appears to have
      been overcome, in the sense that the advantages and disadvantages of these two
      diverse methods have emerged from large and well-performed clinical trials, and
      comparably low doses of anthracyclines and radiotherapy are now used. Challenges
      remain in identifying novel molecular, histological and clinical risk factors for
      stratification of treatment intensity. This could allow a safe reduction in
      therapy for patients known to have an excellent chance of cure with the current
      therapy, while identifying, at diagnosis, the minority of children at risk of
      relapse, who will necessitate more aggressive treatments. Another positive factor
      is the substantial progress that has been made in the cure for recurrent
      patients, with long-term survivals shifting from 30 to almost 60% in more
      recently treated patients with intensive-dose chemotherapy regimens. The
      combination of lower relapses and higher salvage rates translated into
      significantly improved overall survival for Wilms' tumor patients as a whole.
      This review covers current concepts on treatment strategies for Wilms' tumor,
      with an overview of the results and achievements of the important clinical
      trials.

PMID- 16445378
TI  - Stepping-stones to the further advancement of androgen-deprivation therapy for
      prostate cancer.
AB  - Androgen-deprivation therapy has remained the critical therapeutic option for
      patients with advanced prostate cancer for over 60 years. Patients with poorly
      differentiated prostate cancer have low dihydrotestosterone levels in the
      prostate. After androgen-deprivation therapy, dihydrotestosterone levels in the
      prostate remain at approximately 25% of the level measured before therapy. The
      addition of a nonsteroidal anti-androgen to luteinizing hormone-releasing hormone
      analog or surgical castration significantly reduces the risk of all causes of
      death by 8%, which translates into a small, but significant, improvement in the 5
      year survival of 2.9% over castration alone. The biologically aggressive prostate
      cancer cells may have an androgen receptor with heightened sensitivity to low
      dihydrotestosterone levels from the early stage of androgen-dependent disease. It
      is necessary to consider the androgen environment and the status of the androgen
      receptor in the prostate in order to improve the clinical efficacy of androgen
      deprivation therapy and the quality of life of patients.

PMID- 16445379
TI  - Radical radiotherapy for urinary bladder cancer: treatment outcomes.
AB  - The exact value of radiotherapy in the treatment of muscle-invasive bladder
      cancer is difficult to establish, as most studies exploring this issue are
      retrospective with different procedures for selecting patients for treatment, as
      well as varying treatment strategies. An estimate of the 5-year overall survival
      rate following radiotherapy is approximately 35% in consecutive-selected patients
      and approximately 25% in negative-selected patients.

PMID- 16445380
TI  - Combining surgery and chemotherapy for invasive bladder cancer: current and
      future directions.
AB  - More than 13,000 patients died from invasive bladder cancer in 2005 alone.
      Radical cystectomy is the most commonly prescribed treatment for patients with
      muscle-invasive bladder cancer, or for those with a nonmuscle-invasive disease
      that is refractory to intravesical therapy. Despite advances in surgical
      technique and improved understanding of the role of pelvic lymphadenectomy, 5
      year survival probabilities suggest that improvements in treatment are necessary.
      The maturation of several randomized clinical trials on perioperative
      chemotherapy, and particularly neoadjuvant chemotherapy, clearly suggest that an
      integrated treatment program of systemic chemotherapy and definitive locoregional
      therapy may improve the outcome for bladder cancer patients. The next frontier is
      the molecular characterization of this spectrum of diseases that make up invasive
      bladder cancer and targeted therapeutics. Prospective validation of molecular
      markers and evaluation of novel therapeutic agents, alone or in combination with
      established cytotoxic agents, provide hope of better outcomes for bladder cancer
      patients.

PMID- 16445381
TI  - Significance of gene expression analysis of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) describes a family of epithelial tumors arising from
      within the kidney. Each subtype of RCC presents a unique clinical picture with
      varied tumor biology, patient prognosis and response to treatment. Gene
      expression profiling offers the ability to analyze thousands of candidate genes
      in high-throughput arrays and has led to a greater knowledge of the molecular
      genetics of RCC. This powerful technology can identify RCC subtypes,
      recapitulating and refining the current histological classifications. Gene
      expression data also promise to advance current staging systems and improve
      prognostic information for patients and clinicians. Understanding the genetic
      signature of RCC tumors will allow for sophisticated application of systemic and
      targeted therapies, improving patient response and minimizing unnecessary
      exposure of patients to treatment toxicities. This article reviews the
      significance of gene expression analysis in the understanding of tumor biology
      and RCC treatment.

PMID- 16445382
TI  - A proprotein convertase-inhibiting serpin with an endoplasmic reticulum targeting
      signal from Branchiostoma lanceolatum, a close relative of vertebrates.
AB  - Lancelets are considered to take a key position in the evolution of lineages
      leading to vertebrates. Herein, a serpin from the lancelet Branchiostoma
      lanceolatum, Bl-Spn1, was identified that inhibits the PCs (proprotein
      convertases) PC1/3 and furin. The inhibitor forms SDS-stable complexes with
      either of its targets. Analysis of the inhibitor/furin reaction products by mass
      spectroscopy assigns the enzyme's cleavage position C-terminally to Met-Met-Lys
      Arg downward arrow in the reactive site loop of Spn1, in concordance with the
      classical recognition/cleavage site of the principal vertebrate PCs. The
      inhibitor is equipped with a canonical ER (endoplasmic reticulum) retrieval
      signal, Lys-Asp-Glu-Leu (KDEL), marking the inhibitor as a guardian of the
      cellular secretory routes. Deletion of the ER retrieval signal results in the
      export of the inhibitor into the medium of transfected COS-7 cells, consistent
      with the assigned intracellular location. These results identify Bl-Spn1 as the
      first serpin that may inhibit PC1/3-like subtilases at their natural sites of
      action. Phylogenetic comparisons support a concept implying a general role for ER
      residing serpins in the surveillance of subtilase-like enzymes along the
      constitutive and regulated secretory pathways of metazoans including a role in
      the defence of intruders that turn PCs to their propagation.

PMID- 16445383
TI  - Temperature-dependences of the kinetics of reactions of papain and actinidin with
      a series of reactivity probes differing in key molecular recognition features.
AB  - The temperature-dependences of the second-order rate constants (k) of the
      reactions of the catalytic site thiol groups of two cysteine peptidases papain
      (EC 3.4.22.2) and actinidin (EC 3.4.22.14) with a series of seven 2-pyridyl
      disulphide reactivity probes (R-S-S-2-Py, in which R provides variation in
      recognition features) were determined at pH 6.7 at temperatures in the range 4-30
      degrees C by stopped-flow methodology and were used to calculate values of
      DeltaS++, DeltaH++ and DeltaG++. The marked changes in DeltaS++ from negative to
      positive in the papain reactions consequent on provision of increase in the
      opportunities for key non-covalent recognition interactions may implicate
      microsite desolvation in binding site-catalytic site signalling to provide a
      catalytically relevant transition state. The substantially different behaviour of
      actinidin including apparent masking of changes in DeltaH++ by an endothermic
      conformational change suggests a difference in mechanism involving kinetically
      significant conformational change.

PMID- 16445384
TI  - Characterization of the amino acid response element within the human sodium
      coupled neutral amino acid transporter 2 (SNAT2) System A transporter gene.
AB  - The neutral amino acid transport activity, System A, is enhanced by amino acid
      limitation of mammalian cells. Of the three gene products that encode System A
      activity, the one that exhibits this regulation is SNAT2 (sodium-coupled neutral
      amino acid transporter 2). Fibroblasts that are deficient in the amino acid
      response pathway exhibited little or no induction of SNAT2 mRNA. Synthesis of
      SNAT2 mRNA increased within 1-2 h after amino acid removal from HepG2 human
      hepatoma cells. The amino acid responsive SNAT2 genomic element that mediates the
      regulation has been localized to the first intron. Increased binding of selected
      members of the ATF (activating transcription factor) and C/EBP (CCAAT/enhancer
      binding protein) families to the intronic enhancer was established both in vitro
      and in vivo. In contrast, there was no significant association of these factors
      with the SNAT2 promoter. Expression of exogenous individual ATF and C/EBP
      proteins documented that specific family members are associated with either
      activation or repression of SNAT2 transcription. Chromatin immunoprecipitation
      analysis established in vivo that amino acid deprivation led to increased RNA
      polymerase II recruitment to the SNAT2 promoter.

PMID- 16445385
TI  - The epidermal growth factor receptor (EGFR)-S442F mutant displays increased
      affinity for neuregulin-2beta and agonist-independent coupling with downstream
      signalling events.
AB  - The EGFR (epidermal growth factor receptor; ErbB1) is frequently the subject of
      genetic changes in human tumours which contribute to the malignant phenotype by
      altering EGFR signalling. Examples of such genetic changes include
      overexpression, extracellular domain deletions and point mutations, and small
      deletions in the tyrosine kinase domain. We hypothesized that a point mutation in
      one of the EGFR ligand-binding domains would increase the affinity of EGFR for
      NRG2beta (neuregulin-2beta), which is not a potent stimulus of signalling by EGFR
      Wt (wild-type EGFR). This mutation would permit NRG2beta stimulation of EGFR
      signalling in settings in which NRG2beta does not normally do so. To test this
      hypothesis, we have generated and evaluated various EGFR alleles containing
      mutations at Val441 and Ser442. NRG2beta is a much more potent stimulus of the
      EGFR-S442F mutant than of EGFR-Wt. Furthermore, the affinity of NRG2beta for the
      EGFR-S442F mutant is greater than the affinity of NRG2beta for EGFR-Wt. Finally,
      the EGFR-S442F mutant constitutively suppresses apoptosis via phosphoinositide 3
      kinase and Akt signalling but is not highly tyrosine phosphorylated in the
      absence of ligand. These results suggest that mutations in the EGFR ligand
      binding domain in tumours may permit potent stimulation of EGFR signalling by
      ligands that are not normally potent EGFR agonists, thereby providing for a novel
      mechanism by which EGFR signalling may be deregulated. These results also suggest
      that novel EGFR mutations and signalling activities may be responsible for
      deregulated EGFR signalling in tumour cells.

PMID- 16445386
TI  - Two languages, one developing brain: event-related potentials to words in
      bilingual toddlers.
AB  - Infant bilingualism offers a unique opportunity to study the relative effects of
      language experience and maturation on brain development, with each child serving
      as his or her own control. Event-related potentials (ERPs) to words were examined
      in 19- to 22-month-old English-Spanish bilingual toddlers. The children's
      dominant vs. nondominant languages elicited different patterns of neural activity
      in the lateral asymmetry of an early positive component (P100), and the latencies
      and distributions of ERP differences to known vs. unknown words from 200-400 and
      400-600 ms. ERP effects also differed for 'high' and 'low' vocabulary groups
      based on total conceptual vocabulary scores. The results indicate that the
      organization of language-relevant brain activity is linked to experience with
      language rather than brain maturation.

PMID- 16445387
TI  - A shift from diffuse to focal cortical activity with development.
AB  - Recent imaging studies have suggested that developmental changes may parallel
      aspects of adult learning in cortical activation becoming less diffuse and more
      focal over time. However, while adult learning studies examine changes within
      subjects, developmental findings have been based on cross-sectional samples and
      even comparisons across studies. Here, we used functional MRI in children to test
      directly for shifts in cortical activity during performance of a cognitive
      control task, in a combined longitudinal and cross-sectional study. Our
      longitudinal findings, relative to our cross-sectional ones, show attenuated
      activation in dorsolateral prefrontal cortical areas, paralleled by increased
      focal activation in ventral prefrontal regions related to task performance.

PMID- 16445388
TI  - Does human functional brain organization shift from diffuse to focal with
      development?

PMID- 16445389
TI  - Brain development during puberty: state of the science.

PMID- 16445390
TI  - The interplay of learning and development in shaping neural organization.

PMID- 16445391
TI  - A shift from diffuse to focal cortical activity with development: the authors'
      reply.

PMID- 16445392
TI  - Why girls say 'holded' more than boys.
AB  - Women are better than men at verbal memory tasks, such as remembering word lists.
      These tasks depend on declarative memory. The declarative/procedural model of
      language, which posits that the lexicon of stored words is part of declarative
      memory, while grammatical composition of complex forms depends on procedural
      memory, predicts a female superiority in aspects of lexical memory. Other
      neurocognitive models of language have not made this prediction. Here we examine
      the prediction in past-tense over-regularizations (e.g. holded) produced by
      children. We expected that girls would remember irregular past-tense forms (held)
      better than boys, and thus would over-regularize less. To our surprise, girls
      over-regularized far more than boys. We investigated potential explanations for
      this sex difference. Analyses showed that in girls but not boys, over
      regularization rates correlated with measures of the number of similar-sounding
      regulars (folded, molded). This sex difference in phonological neighborhood
      effects is taken to suggest that girls tend to produce over-regularizations in
      associative lexical memory, generalizing over stored neighboring regulars, while
      boys are more likely to depend upon rule-governed affixation (hold+-ed). The
      finding is consistent with the hypothesis that, likely due to their superior
      lexical abilities, females tend to retrieve from memory complex forms (walked)
      that men generally compose with the grammatical system (walk+-ed). The results
      suggest that sex may be an important factor in the acquisition and computation of
      language.

PMID- 16445393
TI  - Toddler subtraction with large sets: further evidence for an analog-magnitude
      representation of number.
AB  - Two experiments were conducted to test the hypothesis that toddlers have access
      to an analog-magnitude number representation that supports numerical reasoning
      about relatively large numbers. Three-year-olds were presented with subtraction
      problems in which initial set size and proportions subtracted were systematically
      varied. Two sets of cookies were presented and then covered. The experimenter
      visibly subtracted cookies from the hidden sets, and the children were asked to
      choose which of the resulting sets had more. In Experiment 1, performance was
      above chance when high proportions of objects (3 versus 6) were subtracted from
      large sets (of 9) and for the subset of older participants (older than 3 years, 5
      months; n = 15), performance was also above chance when high proportions (10
      versus 20) were subtracted from the very large sets (of 30). In Experiment 2,
      which was conducted exclusively with older 3-year-olds and incorporated an
      important methodological control, the pattern of results for the subtraction
      tasks was replicated. In both experiments, success on the tasks was not related
      to counting ability. The results of these experiments support the hypothesis that
      young children have access to an analog-magnitude system for representing large
      approximate quantities, as performance on these subtraction tasks showed a
      Weber's Law signature, and was independent of conventional number knowledge.

PMID- 16445394
TI  - Young children make scale errors when playing with dolls.
AB  - Prior research (DeLoache, Uttal & Rosengren, 2004) has documented that 18- to 30
      month-olds occasionally make scale errors: they attempt to fit their bodies into
      or onto miniature objects (e.g. a chair) that are far too small for them. The
      current study explores whether scale errors are limited to actions that directly
      involve the child's body. We investigated whether children would also make scale
      errors with a doll and objects that were much too small for the doll (e.g. a
      chair, a bed). Many participants did try to fit the doll into or onto the
      miniature objects. Thus, the previously documented phenomenon of scale errors
      extends to situations in which the relevant size difference is between two
      objects. This finding supports the view that scale errors occur when visual
      information about object size fails to influence the decision to act on an
      object. The results are discussed in terms of the use of visual information for
      the planning and control of actions.

PMID- 16445395
TI  - Preference for consonance over dissonance by hearing newborns of deaf parents and
      of hearing parents.
AB  - Behavioral preferences for consonance over dissonance were tested in hearing
      infants of deaf parents and in hearing infants of hearing parents when they were
      2 days old. Using a modified visual-fixation-based, auditory-preference
      procedure, I found that both 2-day-old infants of deaf parents and those of
      hearing parents looked longer at a visual stimulus when looking produced the
      original version of a Mozart minuet as opposed to a version altered to contain
      many dissonant intervals. The relative magnitude of such preference did not
      significantly differ whether their parents were deaf or hearing. Infants prefer
      consonance over dissonance, and the preference is present from birth and is not
      dependent on any specific prenatal or early postnatal experience.

PMID- 16445396
TI  - Event-related potential (ERP) indices of infants' recognition of familiar and
      unfamiliar objects in two and three dimensions.
AB  - We measured infants' recognition of familiar and unfamiliar 3-D objects and their
      2-D representations using event-related potentials (ERPs). Infants differentiated
      familiar from unfamiliar objects when viewing them in both two and three
      dimensions. However, differentiation between the familiar and novel objects
      occurred more quickly when infants viewed the object in 3-D than when they viewed
      2-D representations. The results are discussed with respect to infants'
      recognition abilities and their understanding of real objects and
      representations. This is the first study using 3-D objects in conjunction with
      ERPs in infants, and it introduces an interesting new methodology for assessing
      infants' electrophysiological responses to real objects.

PMID- 16445397
TI  - How fantasy benefits young children's understanding of pretense.
AB  - Sobel and Lillard (2001) demonstrated that 4-year-olds' understanding of the role
      that the mind plays in pretending improved when children were asked questions in
      a fantasy context. The present study investigated whether this fantasy effect was
      motivated by children recognizing that fantasy contains violations of real-world
      causal structure. In Experiment 1, 4-year-olds were shown a fantasy character
      engaged in ordinary actions or actions that violated causal knowledge. Children
      were more likely to say that a troll doll who was acting like but ignorant of the
      character was not pretending to be that character when read the violation story.
      Experiment 2 suggested that this difference was not caused by a greater interest
      in the violation story. Experiment 3 demonstrated a similar difference for
      characters engaged in social and functional violations that were possible in the
      real world. These data are consistent with the hypothesis that preschoolers use
      actions and appearance more than mental states to make judgments about pretense,
      but that those judgments can be influenced by the context in which the questions
      are presented.

PMID- 16445398
TI  - Germs and angels: the role of testimony in young children's ontology.
AB  - In three experiments, children's reliance on other people's testimony as compared
      to their own, first-hand experience was assessed in the domain of ontology.
      Children ranging from 4 to 8 years were asked to judge whether five different
      types of entity exist: real entities (e.g. cats, trees) whose existence is
      evident to everyone; scientific entities (e.g. germs, oxygen) that are normally
      invisible but whose existence is generally presupposed in everyday discourse;
      endorsed beings (e.g. the Tooth Fairy, Santa Claus) whose existence is typically
      endorsed in discourse with young children; equivocal beings (e.g. monsters,
      witches) whose existence is not typically endorsed in discourse with young
      children; and impossible entities (e.g. flying pigs, barking cats) that nobody
      believes in. Children make a broad dichotomy between entities and beings that
      they claim to exist (real entities; scientific entities; and endorsed beings) and
      those whose existence they deny (equivocal beings and impossible entities). They
      also make a more fine-grained distinction among the invisible entities that they
      claim to exist. Thus, they assert the existence of scientific entities such as
      germs with more confidence than that of endorsed beings such as Santa Claus. The
      findings confirm that children's ontological claims extend beyond their first
      hand encounters with instances of a given category. Children readily believe in
      entities that they cannot see for themselves but have been told about. Their
      confidence in the existence of those entities appears to vary with the pattern of
      testimony that they receive.

PMID- 16445399
TI  - Object boundaries influence toddlers' performance in a search task.
AB  - Previous research has shown that young children have difficulty searching for a
      hidden object whose location depends on the position of a partly visible physical
      barrier. Across four experiments, we tested whether children's search errors are
      affected by two variables that influence adults' object-directed attention:
      object boundaries and proximity relations. Toddlers searched for a car that
      rolled down a ramp behind an occluding panel and stopped on contact with a
      barrier. The car's location on each trial depended on the placement of the
      barrier behind one of two doors in the panel. In Experiment 1, when a part of the
      car (a pompom on an antenna) was visible at the same distance from the object as
      the barrier wall in past research, search performance was above chance but below
      ceiling. In Experiments 2 and 3, when the visible part was close to the hidden
      body of the car and could be seen through one of two windows in the doors of the
      occluding panel, performance was near ceiling. In Experiment 4, when only the
      barrier was visible through one of the same windows, performance was at chance.
      Toddlers' search for a hidden object therefore is affected by the proximity of a
      visible part of the object, though not by the proximity of a separate visible
      landmark. These findings suggest a parallel between the object representations of
      young children and those of adults, whose attention is directed to objects and
      spreads in a gradient-like fashion within an object.

PMID- 16445400
TI  - The development of landmark and beacon use in young children: evidence from a
      touchscreen search task.
AB  - Children ages 2, 3 and 4 years participated in a novel hide-and-seek search task
      presented on a touchscreen monitor. On beacon trials, the target hiding place
      could be located using a beacon cue, but on landmark trials, searching required
      the use of a nearby landmark cue. In Experiment 1, 2-year-olds performed less
      accurately than older children on landmark trials but performed equivalently on
      beacon trials. In Experiment 2, the number of items on the screen was reduced and
      2-year-olds' performance improved. Use of the landmark transformation technique
      in Experiment 3 revealed that older children formed a more precise landmark
      target spatial relationship than 2-year-olds. Experiment 4 showed that the
      transformation itself was not responsible for the youngest participants'
      decreased accuracy in Experiment 3. Overall, beacons were utilized effectively by
      all participants, but the use of landmark cues is refined between the ages of 2
      and 4.

PMID- 16445401
TI  - "Free-floating" desmosomes in lipoid proteinosis: an inherent defect in
      keratinocyte adhesion?
AB  - The classic features of lipoid proteinosis - beadlike papules and hoarseness -
      result from the accumulation of hyaline material in the mucocutaneous dermis.
      However, the characteristic manifestation in children - erosive, crusted lesions
      that lead to scarring - is rarely discussed and poorly understood. Lipoid
      proteinosis results from mutations in extracellular matrix protein 1, but the
      function of this protein is largely unknown. We performed ultrastructural studies
      on lesional epidermis, cultured monolayer keratinocytes, and raft keratinocyte
      cultures from blistering lesions of a child with lipoid proteinosis. All sections
      showed the dissociation of relatively intact desmosomes from keratinocytes, with
      desmosomes that were "free-floating" in the intercellular spaces or attached by
      thin strands to the cell membrane. These changes were present in serial sections
      of both tissue and cultured keratinocytes, suggesting this observation to be an
      inherent feature of keratinocytes devoid of extracellular matrix protein 1,
      rather than an artifact. Although additional patients should be studied, the
      diminished appearance of the inner dense plaque - the region of attachment of
      keratin intermediate filaments to desmosomal proteins - provides preliminary
      evidence that extracellular matrix protein 1 may participate in attaching keratin
      intermediate filaments to desmosomal region protein(s).

PMID- 16445402
TI  - Plexiform fibrohistiocytic tumor in three children.
AB  - Plexiform fibrohistiocytic tumor is a very rare fibrohistiocytic tumor of
      intermediate malignancy. It can occur at any age but is more prevalent in
      children and in young adults. Here we present the clinicopathologic findings of
      three girls with this tumor. The patients were 8 months, 14 months, and 7 years
      of age. They each presented with a solitary, nontender, subcutaneous nodule or
      plaque. Light microscopy and immunohistochemical study findings were compatible
      with plexiform fibrohistiocytic tumor. We also review the previously published
      cases in the English-language literature.

PMID- 16445403
TI  - The epidemiology of childhood alopecia areata in China: a study of 226 patients.
AB  - To study the clinical and epidemiologic profile of childhood alopecia areata, we
      performed a survey in which a total of 226 childhood patients less than 16 years
      old were enrolled. Statistical analysis and heritability were performed using EPI
      INFO 6.0, SPSS10.0, and the Falconer method. The median age of onset was 10
      years. The majority of patients (84.96%) presented with limited alopecia. The
      male : female ratio was 1.4:1. Boys appeared to have more severe involvement. The
      earlier the age of onset, the greater the severity of the disease. Sixty-seven
      patients (29.65%) had previous episodes of alopecia areata. Greater severity and
      longer duration were seen in the relapsing patients than in the primary patients.
      Six patients (2.65%) had an associated disease. A positive family history was
      reported in 25 patients (11.06%). The prevalence figures for alopecia areata in
      first-, second-, and third-degree relatives of the probands were 2.87%, 0.40%,
      and 0.13%, respectively. The heritabilities of AA in first-, second-, and third
      degree relatives were 51.20%, 46.25%, and 25.65%, respectively. It can be
      speculated that the effect of genetic factors is important in the occurrence of
      this disease.

PMID- 16445404
TI  - Dermatitis under soccer shin guards: allergy or contact irritant reaction?
AB  - We report a retrospective analysis of eight children aged 9 to 16 years who were
      evaluated for a persistent or recurrent dermatitis that appeared under soccer
      shin guards. To examine the possibility of contact allergy, all had 51 standard
      epicutaneous (patch) tests applied and three or four additional tests comprised
      of pieces of the shin guard components. Tests were read at 48 and 120 hours and
      all were negative in each subject. Irritant contact dermatitis, not allergy, was
      the cause of dermatitis in these subjects. It was postulated that sweating and
      friction contributed to the irritancy.

PMID- 16445405
TI  - Pityriasis lichenoides and idiopathic thrombocytopenic purpura in a young girl.
AB  - Pityriasis lichenoides is an inflammatory skin disorder characterized by
      erythematous, desquamative papules and plaques. An acute form, pityriasis
      lichenoides et varioliformis acuta, and a chronic form, pityriasis lichenoides
      chronica, represent the two ends of the spectrum of this disorder. Most commonly
      seen in children and young adults, its etiology is unknown. We describe a young
      patient with concurrent pityriasis lichenoides and idiopathic thrombocytopenia
      purpura, a previously unreported association.

PMID- 16445406
TI  - The value of MRI in a patient with occult spinal dysraphism.
AB  - We describe an infant girl who was referred to us because of a lumbosacral
      swelling. She was also found to have two nonblanching, erythematous macules, one
      at the cervical level and one at the lumbosacral level. Occult spinal dysraphism
      was demonstrated by magnetic resonance imaging.

PMID- 16445407
TI  - Encephalocraniocutaneous lipomatosis: clinical spectrum of systemic involvement.
AB  - Encephalocraniocutaneous lipomatosis is a rare neurocutaneous syndrome with
      involvement of ectomesodermal tissues. Unilateral lipomatous hamartomas of the
      scalp and eyes are the hallmarks of this disorder. Associated findings are
      extremely variable, ranging from minor abnormalities to severe, debilitating
      disease. We report two unrelated Brazilian patients with encephalocraniocutaneous
      lipomatosis, one presenting with the full-blown spectrum of cutaneous, ocular,
      and central nervous system manifestations, and the other with minor
      extracutaneous manifestations after a 5-year follow-up period.

PMID- 16445408
TI  - Erythromelanosis follicularis faciei et colli associated with keratosis pilaris
      in two brothers.
AB  - Erythromelanosis follicularis faciei et colli is characterized by well-demarcated
      erythema, hyperpigmentation, and follicular papules. Since the original
      description, it has seldom been reported in the literature. We present two
      adolescent brothers who had this disorder associated with keratosis pilaris on
      the shoulders and the extensor surfaces of the arms. Dermatologic examination
      found brown-red pigmentation, erythema, and follicular papules on both maxillary,
      preauricular regions, and the cheeks. The lesions of the older brother were more
      prominent. Histopathologic examination of skin biopsy specimens taken from both
      brothers revealed hyperpigmentation of the basal layer, follicular plugging,
      dermal vascular dilatation and congestion, and perivascular inflammatory
      infiltration. We suggest that the coexistence of these two conditions in brothers
      implies a genetic inheritance and a possible relationship between the disorders.

PMID- 16445410
TI  - Transient aquagenic palmar hyperwrinkling: the first instance reported in a young
      boy.
AB  - Transient reactive papulotranslucent acrokeratoderma is a rare palmoplantar
      keratoderma seen predominantly in adolescent and young adult women. Clinically it
      is characterized by translucent white papules generally involving the palmar
      surfaces after exposure to water. The typical "hands-in-the-bucket" sign, which
      is not clearly visible until the hand is submerged in water, is indispensable for
      the diagnosis. Histologic examination shows a mild orthokeratotic hyperkeratosis
      and dilated eccrine ducts. We propose the term "transient aquagenic palmar
      hyperwrinkling" to describe this condition. Until now, a total of 12 patients
      have been reported in the literature, all female, with an age of onset from 9 to
      33 years. We present the first reported instance of this condition in a young
      boy.

PMID- 16445409
TI  - Disseminated hyperkeratotic and granulomatous nodules in a child with fatal
      Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis is a rare and potentially fatal syndrome
      associated with a variety of genetic, malignant, autoimmune, or infectious
      conditions. The importance of cutaneous presentations of this syndrome has only
      recently been brought forward. We report the first case of Epstein-Barr-virus
      associated hemophagocytic lymphohistiocytosis presenting with papulonodular and
      granulomatous skin lesions. A girl of African origin developed several
      umbilicated papules on her extremities and face at the age of 18 months. She was
      born in Germany, had never visited Africa, and was otherwise healthy. Over the
      next 5 months the lesions progressed in size and number and became
      hyperkeratotic. Histopathologic analysis of early lesions revealed a superficial
      lympho- and plasmacellular dermatitis with some features of panniculitis. Later
      biopsy specimens from nodular lesions showed the formation of tuberculoid
      granulomas in the deep dermis. At the age of 23 months she became severely ill,
      rapidly developing high fever, hepatosplenomegaly, icterus, pancytopenia, and
      ascites. On the basis of bone marrow and lymph node biopsies, the diagnosis of
      hemophagocytic lymphohistiocytosis was established. However, this phenomenon
      could not be detected in any of the skin specimens. An active Epstein-Barr virus
      infection was diagnosed by polymerase chain reaction in blood, lymphoid tissue,
      and skin. Despite chemotherapy with etoposide and cortisone, the girl expired 14
      days after clinical onset of her systemic disease.

PMID- 16445411
TI  - Infantile Crohn disease presenting with diarrhea and pyoderma gangrenosum.
AB  - Cutaneous erosions and ulcerations in the diaper area are common in infancy and
      usually result from local irritation. We describe an infant with chronic diarrhea
      and failure to thrive who developed extensive ulcerations in the inguinal folds
      and perineum that were initially thought to be exclusively caused by local
      irritation. A cutaneous examination found signs consistent with those of pyoderma
      gangrenosum, leading to a diagnosis of infantile Crohn disease. Cutaneous signs
      can lead to the diagnosis of an underlying systemic disease in infants with
      chronic diarrhea and rash. Prompt diagnosis is especially important in infantile
      Crohn disease, since many infants require surgical resection of affected bowel,
      and 60% die from disease complications. This article reports a rare instance of
      an infant who developed pyoderma gangrenosum due to Crohn disease and reviews
      cutaneous signs of systemic disease in infants presenting with chronic diarrhea
      and rash.

PMID- 16445412
TI  - Cutaneous Crohn disease in a child.
AB  - Cutaneous Crohn disease refers to granulomatous skin manifestations not
      contiguous with gastrointestinal affected areas. It is a very rare condition,
      especially in children, and is easily misdiagnosed when characteristic
      gastrointestinal symptoms are absent. We report a 10-year-old Caucasian girl with
      a 6-month history of erythematous, firm tumescence of the left labium majus
      pudendi and moist vegetations circumscribing the anal ostium. Histologic analysis
      of skin biopsy specimens from both types of lesions showed a characteristic
      granulomatous noncaseating infiltrate throughout the dermis. Endoscopic
      examination and a colon biopsy specimen showed chronic granulomatous inflammation
      consistent with Crohn disease. Treatment with prednisolone 20 mg daily,
      metronidazole 250 mg three times daily, topical corticosteroids, and mupirocin
      ointment produced marked improvement of the vulvar edema, whereas the perianal
      lesion had a relapsing course. Early recognition of extra-intestinal
      manifestations of Crohn disease, which are extremely rare in children, may be
      difficult. Coexistence of contiguous and noncontiguous lesions, representing the
      very first signs of the disease, are further peculiarities in our patient.

PMID- 16445413
TI  - Juvenile xanthogranuloma of the finger.
AB  - We present an unusual instance of juvenile xanthogranuloma occurring in the hand.
      A 23-month-old girl had a mass on the radial aspect of the right third finger at
      the distal interphalangeal joint that extended to the collateral ligament. The
      lesion was histologically diagnosed as a juvenile xanthogranuloma after resection
      of the mass. Juvenile xanthogranuloma is uncommon in the hand, and only three
      patients with this condition occurring in the digits have been reported in the
      English language literature. The clinical presentation, diagnosis, and treatment
      are discussed.

PMID- 16445414
TI  - A midline cyst containing clear fluid in an infant and review of management.
AB  - A 3-month-old healthy girl had a cyst present from birth, located in the midline,
      in the area of the anterior fontanel. A magnetic resonance imaging was performed
      at age 7 months, which did not show communication between the cyst and the
      central nervous system. At a subsequent examination, while the cyst was being
      probed, it broke and expressed clear fluid. The cyst was subsequently removed
      surgically and was found histopathologically to be an epidermal inclusion cyst
      without communication with the central nervous system. Epidermal inclusion cysts
      very rarely occur on the midline in the area of the anterior fontanel, and none
      have been reported to contain clear fluid. Their proper management requires
      focused clinical assessment, noninvasive imaging, and consideration of surgical
      removal, in particular, if they communicate with the intracranial space.

PMID- 16445415
TI  - One-year survey of cutaneous lesions in 1000 consecutive Iranian newborns.
AB  - Our objective was to study skin disorders in neonates within the first 48 hours
      of life in Ahvaz, Iran. One thousand consecutive neonates were examined in a
      descriptional prospective cohort study for 1 year (2002-03). The rate of skin
      disorders and their relationship to age of gestation and sex were calculated and
      analyzed using the computerized program SPSS version 10 and chi-squared test
      (chi2). Our findings were Mongolian spots (71.3%), Epstein pearls (70.2%),
      sebaceous hyperplasia (43.7%), salmon patch (26.2%), hypertrichosis (25.7%),
      erythema toxicum (11.1%), milia (7.5%), desquamation (1.9%), hemangioma (1.3%),
      and miliaria (1.3%). The most frequent skin disorders were Mongolian spots,
      Epstein pearls, and sebaceous hyperplasia. Differences between our study findings
      and those of others may be based on racial differences and study method.

PMID- 16445416
TI  - An epidemic airborne disease caused by the oak processionary caterpillar.
AB  - The oak processionary caterpillar (Thaumetopoea processionea Lepidoptera) is
      found in several European countries. It usually lives in oak forests or on single
      standing oak trees. The larva of from the 3rd to 6th developmental stage (instar)
      develops poisonous hair (setae), filled with an urticating toxin that may lead to
      serious dermatitis, conjunctivitis, and pulmonary affection (summarized as
      lepidopterism) on contact with the setae. In June 2004 more than 40 people
      including young children developed symptoms of lepidopterism after resting within
      20 m of an infested oak tree. Only a few people had touched the caterpillars. All
      those with clinical symptoms of lepidopterism could be treated as outpatients,
      but several needed systemic steroids because of the severity of their complaints.
      Lepidopterism, an airborne disease caused by the setae of the processionary
      caterpillar, is a growing public health problem because of the increasing numbers
      of outbreaks.

PMID- 16445417
TI  - Etanercept for psoriasis in the pediatric population: experience in nine
      patients.
AB  - Psoriasis commonly affects children and adolescents, and the need for safe,
      effective therapy is a special consideration in the pediatric population. In
      recent years, the use of targeted immunomodulatory biologic agents has been
      increasingly studied for the treatment of psoriasis. Of these, etanercept, a
      tumor necrosis factor-alpha antagonist, has been approved for the treatment of
      psoriasis and psoriatic arthritis in adults, and while it is approved for use in
      juvenile rheumatoid arthritis, formal studies are needed to demonstrate its
      safety and efficacy for childhood psoriasis. We present our preliminary
      experience of treating nine pediatric patients with generalized, recalcitrant
      psoriasis with etanercept therapy.

PMID- 16445418
TI  - Clearance of generalized papular umbilicated granuloma annulare in a child with
      bath PUVA therapy.
AB  - Papular umbilicated granuloma annulare is usually localized and is relatively
      asymptomatic. The generalized condition is rarely reported in children and tends
      to respond less well to treatment than the localized form. We report the first
      instance of generalized papular umbilicated granuloma annulare in an 11-year-old
      boy, which cleared following bath psoralen plus ultraviolet A therapy.

PMID- 16445419
TI  - Successful treatment of laryngeal stenosis in laryngo-onycho-cutaneous syndrome
      with topical mitomycin C.
AB  - Laryngo-onycho-cutaneous syndrome is a very rare entity found in Punjabi
      families. It affects the skin, nails, and larynx. Laryngeal involvement may cause
      lethal airway obstruction, and has in the past proved very difficult to treat.
      Mitomycin C is an antibiotic that acts as an alkylating agent, inhibiting DNA
      synthesis. It reduces fibroblast proliferation, and has previously been used to
      treat choanal atresia and laryngeal stenosis. We report an 18-year-old man with
      complete transglottic laryngeal stenosis secondary to laryngo-onycho-cutaneous
      syndrome. An airway was established by dissection with a bougie and sickle knife,
      and was initially maintained by the upper limb of a Montgomery T-tube. Laryngeal
      granulation tissue present on removal of the T-tube was treated with topical
      mitomycin C (2 mg/mL) applied for 4 minutes on two occasions with an interval of
      1 month. A year later, the airway remained patent, with no granulation tissue.

PMID- 16445420
TI  - Cutaneous leishmaniasis: three children with Leishmania major successfully
      treated with itraconazole.
AB  - We report the rare instance of four family members with numerous cutaneous
      lesions of Leishmania major contracted while on holiday in Algeria. Treatment was
      successful with oral itraconazole for the children and intralesional sodium
      stibogluconate for the mother. Cutaneous leishmaniasis should be considered in
      those with apparently sterile plaques returning from endemic areas. These results
      suggest that itraconazole, which is ideally suited for use in children, is an
      effective monotherapy for L. major.

PMID- 16445421
TI  - What syndrome is this? KID syndrome (keratitis, ichthyosis, deafness).

PMID- 16445422
TI  - Large plantar mass in a newborn.

PMID- 16445423
TI  - Mosaicism in genetic skin disorders.

PMID- 16445425
TI  - Congenital skin lesions presenting as morphea in a 4-year-old.

PMID- 16445426
TI  - Bilateral xanthelasma palpebrarum on both eyelids in a 9-year-old boy.

PMID- 16445427
TI  - Actinic prurigo in an Albanian girl.

PMID- 16445428
TI  - Verrucous epidermal nevus with unusual features.

PMID- 16445429
TI  - Nevoid basal cell carcinoma syndrome in an adolescent boy.

PMID- 16445430
TI  - Benign cephalic histiocytosis preceding the development of insulin-dependent
      diabetes mellitus.

PMID- 16445431
TI  - Atopic dermatitis and nutritional rickets: an exercise in parental counseling.

PMID- 16445432
TI  - XXXVII Nordic Ophthalmological Congress, 2006.

PMID- 16445433
TI  - Age-related maculopathy and the impact of blue light hazard.
AB  - The pathogenesis of age-related maculopathy (ARM), the most common cause of
      visual loss after the age of 60 years, is indeed a complicated scenario that
      involves a variety of hereditary and environmental factors. The pathological
      cellular and molecular events underlying retinal photochemical light damage,
      including photoreceptor apoptosis, have been analysed in experimental animal
      models. Studies of age-related alterations of the retina and photoreceptors, the
      accumulation of lipofuscin in retinal pigment epithelium (RPE) cells, and the
      formation of drusen have greatly contributed to our knowledge. A new concept of
      an inflammatory response to drusen has emerged, suggesting immunogenic and
      systemic reactions in Bruch's membrane and the subretinal space. Oxidative stress
      and free radical damage also impact on the photoreceptors and RPE cells in the
      ageing eye. Based on the photoelectric effect, a fundamental concept in quantum
      physics, the consequences of high-energy irradiation have been analysed in animal
      models and cell culture. Short-wavelength radiation (rhodopsin spectrum), and the
      blue light hazard (excitation peak 440 nm), have been shown to have a major
      impact on photoreceptor and RPE function, inducing photochemical damage and
      apoptotic cell death. Following cataract surgery, there is a dramatic change in
      ocular transmittance. In aphakic or pseudophakic eyes (with clear intraocular
      lenses), high-energy (blue) and ultraviolet-A radiation strikes the retina.
      Epidemiological data indicate a significantly increased 5-year incidence of late
      ARM in non-phakic eyes compared with phakic eyes. In recent years, putative
      prophylactic measures against ARM have emerged. The implantation of 'yellow'
      intraocular lenses (IOLs) that absorb high-energy blue radiation is, from a
      theoretical point of view, the most rational approach, and, from a practical
      point of view, is easy to accomplish. With increasing age, RPE cells accumulate
      lipofuscin (chromophore A2E). It is noteworthy that the yellow IOL not only
      protects A2E-laden human RPE cells from blue light (peak 430 nm) damage, but also
      alleviates the detrimental effects of green (peak 550 nm) and white light. A
      prophylactic treatment using antioxidants is aimed at counteracting oxidative
      stress and free radical cellular damage. The Age-Related Eye Disease Study
      (AREDS), a randomized clinical trial, showed a significantly lower incidence of
      late ARM in a cohort of patients with drusen maculopathy treated with high doses
      of antioxidants than in a placebo group. In recent years, considerable progress
      in retinal research has been achieved, creating a platform for the search for new
      prophylactic and therapeutic measures to alleviate or prevent photoreceptor and
      RPE degeneration in ARM.

PMID- 16445434
TI  - Visual prognosis after panretinal photocoagulation for proliferative diabetic
      retinopathy.
AB  - INTRODUCTION: Proliferative diabetic retinopathy is treated with panretinal
      photocoagulation, which improves the visual prognosis in this complication
      considerably. The visual acuity (VA) and grade of retinopathy before treatment
      are known indicators of the visual prognosis after treatment, but the prognostic
      value of other clinical background and treatment parameters is unknown. METHODS:
      The study reports predictors for visual outcome identified among retrospective
      clinical background data and treatment parameters from 4422 panretinal
      photocoagulation sessions for proliferative diabetic retinopathy in 1013 eyes of
      601 patients performed at the Department of Ophthalmology, Arhus University
      Hospital between 1985 and 2002. RESULTS: High pretreatment VA and low age were
      strong positive predictors of post-treatment VA (p < 0.0001). However, diabetes
      type, diabetes duration and calendar year of treatment showed no influence on
      post-treatment VA (p = 0.7829, 0.1782, and 0.3747, respectively). The visual
      prognosis was inversely related to the number of treatment sessions (p = 0.0259)
      and the number of vitrectomies (OR = 2.66 [1.24; 5.69], p = 0.0117, for more than
      two operations). However, the visual prognosis was unrelated to any of the other
      parameters studied. CONCLUSIONS: Pretreatment VA, age and the number of
      panretinal photocoagulation treatment sessions and vitrectomies necessary to halt
      the disease are indicators of the visual prognosis after panretinal laser
      photocoagulation for proliferative diabetic retinopathy.

PMID- 16445435
TI  - Laser photocoagulation for retinopathy of prematurity: structural and functional
      outcome.
AB  - BACKGROUND: To report the structural and refractive outcome after laser
      photocoagulation for retinopathy of prematurity (ROP). METHODS: Nineteen
      consecutive patients who had undergone photocoagulation for ROP between 1997 and
      2002 at our clinic were examined for this non-comparative, consecutive,
      interventional, retrospective case series. A total of 37 eyes received either
      transscleral or transpupillary laser treatment. Data consisted of grade of ROP
      pre- and postoperatively, birth weight, perioperative and postoperative
      complications and refraction. Based on indirect ophthalmoscopy, independent
      observers graded the extent of ROP and determined the postoperative refraction by
      retinoscopy. RESULTS: A total of 97% of all eyes responded to laser treatment
      with regression of ROP. Only one eye out of 37 progressed to stage IV B despite
      photocoagulation and therefore an encircling procedure was performed. After
      further progression a vitrectomy was carried out. Perioperative complications
      included haemorrhages in 22% that resorbed spontaneously and cataract formation
      in one eye (3%). Postoperative refractive errors at mean ages of 23 +/- 12 months
      and 45 +/- 14 months were evaluated in 15/19 patients (79%). The spherical
      equivalents ranged between -8 D and +6 D at the first examination and between -12
      D and +7 D at the second examination. In all only 14% of the refracted eyes were
      myopic. CONCLUSIONS: Photocoagulation for ROP in our patients resulted in
      regression of threshold ROP. In addition, the analyses of the refractive outcomes
      demonstrated a predominance of hypermetropia in our patients.

PMID- 16445436
TI  - Retinal function following transpupillary thermotherapy for occult choroidal
      neovascularization in age-related macular degeneration: a short-term study by
      focal electroretinography.
AB  - PURPOSE: To assess short-term changes in macular function after transpupillary
      thermotherapy (TTT) in patients with occult subfoveal choroidal
      neovascularization (CNV) secondary to age-related macular degeneration (AMD),
      using focal electroretinography (FERG). METHODS: Twenty-five patients with occult
      subfoveal CNV due to AMD were treated with TTT delivered using an infrared (810
      nm) diode laser (spot size 3.0 mm, laser power 400-600 mW, duration 60 seconds).
      All patients were clinically evaluated before, 1 and 6 weeks after treatment.
      Snellen visual acuity (VA) was measured at each visit. Fluorescein angiography
      (FA) was performed at baseline and 6 weeks after TTT. Focal ERGs were recorded in
      all patients immediately before and 1 week after TTT in response to an 18-degree
      diameter, 41 Hz flickering spot (630 nm) centred on the fovea, presented on a
      steady background in Maxwellian view. A subgroup of 12 patients was also re
      tested by FERG at 6-weeks post-TTT. RESULTS: No significant changes in mean FERG
      amplitude and phase were observed across the different recording sessions before
      and after TTT. One week after TTT, four patients had significant (> 2 SD from
      baseline variability) increases in FERG amplitude and/or phase advances, one had
      a decrease in amplitude and four had phase delays, compared to baseline. The
      remaining 15 patients had stable FERGs. Six weeks after TTT, four patients had
      significant increases in FERG amplitude and/or phase advances, four had decreases
      in amplitude and/or phase delays, and four had stable FERGs, compared to
      baseline. Improvement in FERG parameters after TTT was always associated with an
      improvement in VA and a decrease in exudation. Patients with post-TTT FERG
      deterioration had stable or deteriorated clinical pictures. At either 1 or 6
      weeks post-TTT, the FERG amplitude increase was inversely correlated (p < 0.05)
      with the baseline FERG amplitude and VA. CONCLUSIONS: Three major conclusions can
      be drawn: in a short-term follow-up, TTT was not found to be associated with
      significant changes in macular function; FERG improvement was associated with VA
      improvement, and the increase in FERG amplitude was greatest in patients with the
      worst baseline acuity.

PMID- 16445437
TI  - Visual impairment in Finnish Usher syndrome type III.
AB  - PURPOSE: To evaluate visual impairment in Finnish Usher syndrome type 3 (USH3)
      and compare this with visual impairment in Usher syndrome types 1b (USH1b) and 2a
      (USH2a). METHODS: We carried out a retrospective study of 28 Finnish USH3
      patients, 24 Dutch USH2a patients and 17 Dutch USH1b patients. Cross-sectional
      regression analyses of the functional acuity score (FAS), functional field score
      (FFS*) and functional vision score (FVS*) related to age were performed for all
      patients. The FFS* and FVS* were calculated using the isoptre V-4 test target
      instead of the usual III-4 target. Statistical tests relating to regression lines
      and Student's t-test were used to compare between USH3 patients and the other
      genetic subtypes of Usher syndrome. RESULTS: Cross-sectional analyses revealed
      significant deterioration in the FAS (1.3% per year), FFS* (1.4% per year) and
      FVS* (1.8% per year) with advancing age in the USH3 patient group. At a given age
      the USH3 patients showed significantly poorer visual field function than the
      USH2a patients. CONCLUSIONS: The rate of deterioration in visual function in
      Finnish USH3 patients was fairly similar to that in Dutch USH1b or USH2a
      patients. At a given age, visual field impairment in USH3 patients was similar to
      that in USH1b patients but poorer than in USH2a patients.

PMID- 16445438
TI  - An isotonic preparation of 1 mg/ml indocyanine green is not toxic to
      hyperconfluent ARPE19 cells, even after prolonged exposure.
AB  - PURPOSE: To investigate the in vitro toxicity of indocyanine green and
      infracyanine green (ICG) to cultured ARPE19 cells, in particular with respect to
      the concentration and time dependence of this toxicity. METHODS: ARPE19 cells
      were grown for at least 1 week past confluence (hyperconfluent cells) before
      being subjected to challenge with ICG. Cell survival was tested with the MTT
      assay. RESULTS: When applied in isotonic solutions, ICG in all concentrations
      (below 5 mg/ml) and at all exposure times tested (2 mins-2 hours) was found not
      to affect the survival of ARPE19 cells. ARPE19 cultures older than 30 days were
      more resistant to a 5 mg/ml hypotonic ICG solution than younger cultures.
      CONCLUSION: When toxicity of ICG was tested in hyperconfluent ARPE19 cultures,
      these cells were found to be more resistant to the dye than has been previously
      reported for more immature ARPE19 cells.

PMID- 16445439
TI  - PaCE: a technique to avoid subretinal fluid drainage in retinal detachment
      surgery.
AB  - PURPOSE: Subretinal fluid (SRF) drainage and thus the potential complications of
      this procedure during scleral buckling can be avoided by inducing SRF absorption
      preoperatively. The technique described in this series is named PaCE (Pneumatic
      Cryo Explant). METHODS: A total of 22 eyes of 22 patients with primary bullous
      rhegmatogenous retinal detachment (RRD) were included in this prospective non
      comparative case trial. All satisfied specific inclusion criteria similar to
      those used in previous pneumatic retinopexy (PR) studies. Under direct
      visualization, 0.3 ml C3F8 100% was injected into the vitreous cavity through the
      pars plana. Postoperative posturing was encouraged. Retinopexy with either
      cryotherapy or laser was performed, combined with scleral buckling (SB) when the
      SRF was absorbed. Avoidance of SRF drainage and persistent reattachment of the
      retina at the end of the 12-month follow-up was considered a successful outcome.
      A change in vision by one line (logMAR) was considered significant. RESULTS:
      Resolution of SRF before retinopexy and the SB procedure was achieved in 20 of 22
      eyes (90.9%) and hence SRF drainage was not required. Visual improvement was
      achieved in 95% of cases. One eye (4.5%) lost vision due to a total RD after gas
      injection (further surgery was not carried out). CONCLUSION: PaCE should be
      considered in any suitable case of primary RRD where SRF drainage is deemed
      necessary. The potential complications associated with this procedure are
      relatively less serious and it does not compromise the viability of subsequent
      procedures.

PMID- 16445440
TI  - Effects of intraperitoneal vitamin E, melatonin and aprotinin on leptin
      expression in the guinea pig eye during experimental uveitis.
AB  - PURPOSE: To observe ultrastructural changes and leptin expression in the guinea
      pig eye during experimental uveitis (EU) and the effects of vitamin E, melatonin
      and aprotinin on leptin expression. METHODS: Thirty male guinea pigs were
      randomly classified into five groups. Group 1 was the control group. Groups 2, 3,
      4 and 5 received intravitreal injections of bovine serum albumin (BSA) to induce
      EU. At the same time on the third day, groups 3 (EU + vitamin E), 4 (EU +
      melatonin) and 5 (EU + aprotinin) received intraperitoneal vitamin E (150 mg/kg),
      melatonin (10 mg/kg) and aprotinin (20,000 IU/kg), respectively. On the sixth
      day, histopathological and clinical scoring of inflammation were performed, and
      leptin expression was investigated in the retina, choroid, sclera, episclera and
      cornea, and compared. RESULTS: There was a remarkable increase in leptin
      expression in the retina, choroid, sclera and episclera in the EU group. Leptin
      expression in the treatment groups was similar to that in the control group. At
      light and electron microscopic levels, ganglion cells were oedematous and inner
      plexiform layer thickness had increased in the EU group retinas. Oedema was
      decreased in the treatment groups. Comparison of the EU and treatment groups
      revealed significant differences histopathologically and clinically. CONCLUSION:
      Experimental uveitis causes an increase in leptin expression in the retina,
      choroid, sclera and episclera of guinea pigs. Vitamin E, melatonin and aprotinin
      inhibit this increase. Leptin seems to be closely related to ocular inflammation.

PMID- 16445441
TI  - The pathogenesis of optic disc splinter haemorrhages: a new hypothesis.
AB  - PURPOSE: To describe a hypothesized relationship between optic disc haemorrhages
      (ODHs) and primary vascular dysregulation (PVD). METHODS: Observational case
      report of a patient with classical PVD and five bilateral recurrent ODHs RESULTS:
      The ODHs were superotemporal in the right eye and inferotemporal in the left; the
      eyes were otherwise normal. Intraocular pressure (IOP) never exceeded 17 mmHg.
      Visual fields were normal. Increased blood flow resistivity, a reduced blood flow
      of the extraocular vessels, a low systemic blood pressure, a cold-induced flow
      stop of the nailfold capillaries, and elevated endothelin-1 plasma levels were
      found, all confirming the diagnosis of vascular dysregulation. CONCLUSIONS: Optic
      disc haemorrhages may be due to a disturbed blood-retina barrier rather than to a
      mechanical rupture of the vessel. This barrier dysfunction may occur in the
      context of PVD.

PMID- 16445442
TI  - Cardiovascular risk factors and events in glaucoma patients with peripapillary
      focal arteriolar narrowing.
AB  - PURPOSE: To evaluate cardiovascular risk factors and events in glaucoma patients
      with and without peripapillary focal arteriolar narrowing of retinal vessels.
      METHODS: We examined the fundus photographs of 325 consecutive glaucoma patients
      for evidence of focal arteriolar narrowing of retinal vessels adjacent to the
      optic disc. Cases and controls were matched for age, race, sex and mean deviation
      on Humphrey visual field. Medical information regarding cardiovascular risk
      factors and events was collected from patients' primary care physicians, and this
      information was confirmed by questionnaires sent to the patients themselves.
      RESULTS: A total of 58 pairs of cases and controls were matched. The prevalence
      of hypertension and diabetes was exactly equal in both groups, 65.5% and 27.6%,
      respectively. Similarly, the prevalences of myocardial infarction, cardiac
      surgery, angioplasty, family history of heart disease and smoking were nearly
      identical in both groups. There was no significant difference in the prevalence
      of strokes or transient ischaemic attacks. The prevalence of hypercholesterolemia
      and mortality was greater in the case group (mean differences of 8.6, p = 0.42
      and 5.2, p = 0.25, respectively), however, these differences were not
      statistically significant. CONCLUSION: There is no significant relationship
      between peripapillary focal arteriolar narrowing of retinal vessels and
      cardiovascular risk factors or events in patients with glaucoma. Proximal
      narrowing does not appear to be a marker of systemic vascular disease.

PMID- 16445443
TI  - A multicentre, retrospective study of resource utilization and costs associated
      with glaucoma management in France and Sweden.
AB  - PURPOSE: To assess resource utilization and costs associated with glaucoma
      management in France and Sweden. METHODS: A total of 267 patient records (121 in
      France, 146 in Sweden) with diagnoses of primary open-angle glaucoma (POAG) and
      ocular hypertension (OH), treated medically, were reviewed for a 2-year period
      (beginning during 1997-99) for relevant clinical and resource utilization data.
      Economic data were applied to estimate treatment costs. RESULTS: The annual cost
      of treating glaucoma was estimated at SEK5305 (531 euro )/patient in Sweden and
      390 euro/patient in France. In both countries, medication costs comprised about
      half of the total costs. Surgical procedures and hospitalizations represented
      greater proportions of total cost in France (7.0% and 9.6%, respectively) than in
      Sweden (3.7% and 0.6%, respectively). CONCLUSION: Medication costs represent a
      high proportion of total treatment costs. These findings highlight the relative
      importance of medical therapy and of assessing the cost-effectiveness of
      medications in glaucoma.

PMID- 16445444
TI  - Socioeconomic differences in glaucoma patients' knowledge, need for information
      and expectations of treatments.
AB  - PURPOSE: To study the specific items for which socioeconomic differences in
      glaucoma patients' knowledge, need for information and expectations of treatments
      exist, with the aim of developing a patient education programme. METHODS: A total
      of 44 randomly selected ophthalmologists assigned 166 consecutive outpatient
      glaucoma patients to complete a questionnaire that had been systematically
      developed based on focus group interviews, suggestions from several experts and a
      pilot test. Topics included knowledge about glaucoma and its treatment, need for
      information and expectations of treatment. Educational level was used as a
      measure for socioeconomic status. Logistic regression analysis was conducted to
      adjust for age, sex and duration of glaucoma. RESULTS: After adjusting for age,
      sex and duration of glaucoma, knowledge of glaucoma and its treatment was found
      to be positively correlated with socioeconomic status. Items on knowledge with
      socioeconomic differences concerned risk factors, pathophysiology and
      consequences of glaucoma, as well as effects and adverse effects of treatments.
      The lowest socioeconomic group demonstrated more need for information on public
      assistance and practical aspects of glaucoma and more often expected that
      glaucoma damage could be repaired. CONCLUSION: Important socioeconomic
      differences in knowledge, need for information and expectations of treatment
      exist in glaucoma patients. Patient education should focus on every glaucoma
      patient, but better information for the lower socioeconomic groups about specific
      items mentioned in this study might reduce the negative effects of low
      socioeconomic status on visual impairment.

PMID- 16445445
TI  - Colour vision and retinal nerve fibre layer photography in patients with an
      Acrysof Natural intraocular lens.
AB  - PURPOSE: To study colour vision and retinal nerve fibre layer (RNFL) photographs
      in patients with an Acrysof Natural intraocular lens (IOL). METHODS: We carried
      out a randomized double-blind study. An Acrysof Natural IOL (model SN60AT) was
      implanted in 25 eyes of 19 patients and an Acrysof IOL (model SA60AT) was
      implanted in 27 eyes of 18 control patients. The patients returned for colour
      vision tests and fundus photography 1-6 months after the surgery. RESULTS:
      Standard pseudoisochromatic plates, part 2, were correctly interpreted and the
      Farnsworth-Munsell 100-hue test (FM 100) total and individual box scores were
      normal in all IOL eyes. In the FM 100 hue test there were no significant
      differences in the results of the total error scores or the error scores of the
      individual boxes between the eyes with Acrysof Natural and those with Acrysof
      lenses. The yellow coloration of the Acrysof Natural IOL did not affect the
      visibility of the RNFL in photographs. CONCLUSIONS: The Acrysof Natural IOL did
      not affect colour vision in the tested patients, even in the blue region of the
      spectrum, and can be implanted in patients who need to have normal colour vision
      for the purposes of their occupation. The Acrysof Natural IOL does not interfere
      with RNFL photography and can also be used in patients with glaucoma.

PMID- 16445446
TI  - Visual outcomes with the yellow intraocular lens.
AB  - PURPOSE: To compare postoperative best distance visual acuity (VA), contrast
      sensitivity and colour perception with the blue light-filtering AcrySof Natural
      (SN60AT) and AcrySof single-piece (SA60AT) intraocular lenses (IOLs). METHODS:
      This was a prospective, randomized, comparative, interventional study comparing
      postoperative performance between the SN60 and SA60 IOLs. There were nine
      patients (nine eyes) in the SN60 group and 10 patients (10 eyes) in the SA60
      group. All patients were operated using phacoemulsification. Postoperative VA
      (Snellen chart), contrast sensitivity (Pelli-Robson contrast sensitivity chart)
      and colour perception (Farnsworth-Munsell D-15 panel test) were measured at 1, 3
      and 6 months postoperatively. RESULTS: Postoperative best corrected VA after 6
      months was 20/20 or better in 89% of SN60 eyes and 100% of SA60 eyes.
      Postoperative contrast sensitivity scores improved significantly in both groups
      under both photopic and mesopic conditions. There were no statistically
      significant differences in contrast sensitivity scores between the SN60 and SA60
      groups at any of the postoperative evaluation time-points. Postoperative colour
      perception improved significantly in both the SN60 and SA60 groups, and there
      were no statistically significant differences in colour perception performance
      between the two groups. CONCLUSION: The blue light-filtering AcrySof Natural
      (SN60) IOL has postoperative visual performance comparable with that of the
      AcrySof single-piece (SA60) IOL.

PMID- 16445447
TI  - Redilatation with intracameral mydriatics in phacoemulsification surgery.
AB  - PURPOSE: To determine whether intracameral mydriatics can redilate pupils that
      contract during phacoemulsification cataract surgery. METHODS: A total of 80
      patients were included in this prospective, randomized, double-blind study
      performed at Ornskoldsviks Hospital Eye Clinic. Of these, 60 patients had 0.6
      microg/ml of epinephrine added to the balanced salt solution (BSS) used for
      irrigation and 20 patients did not. The patients in each group were randomized
      and given either an intracameral mydriatics (ICM) solution or placebo
      intracamerally after phacoemulsification and cortex cleaning. The pupil size was
      registered preoperatively, after cortex cleaning, 30 seconds after study
      injection, 2 mins after study injection and the day after surgery. RESULTS: No
      clinically relevant differences were found preoperatively. In the epinephrine
      material a significantly longer operation time (p = 0.023) and more procedures
      requiring Vision Blue and Kelman-type tip in the placebo group might indicate
      diversity in the grade of cataract. There was a greater degree of contraction in
      the absence of epinephrine in the irrigation solution (2.3 +/- 1.0 mm in the ICM
      group and 3.2 +/- 0.7 mm in the placebo group) compared to in the presence of
      epinephrine. With no epinephrine ICM significantly redilated the pupils at 30
      seconds (p < or = 0.001) as well as at 2 mins (p = 0.015). CONCLUSION: We have
      shown that in cases with an intraoperative pupil contraction, ICM is effective in
      redilating the pupil. Insufficient adrenergic stimulation of the pupil dilator
      appears to be a major factor causing intraoperative pupil contraction during
      phacoemulsification cataract surgery.

PMID- 16445448
TI  - Limbal anaesthesia versus topical anaesthesia for clear corneal
      phacoemulsification.
AB  - PURPOSE: To compare the safety and clinical efficacy provided by limbal
      anaesthesia with topical anaesthesia in cataract surgery. METHODS: A total of 117
      consecutive patients undergoing routine cataract surgery were randomly assigned
      to receive limbal or topical anaesthesia. Limbal anaesthesia was administered
      with a cellulose ophthalmic sponge soaked in preservative-free lidocaine
      hydrochloride 4% applied to the temporal perilimbal area for 45 seconds
      immediately before surgery. For topical anaesthesia lidocaine 4% was instilled in
      each patient at 10-min intervals four times before surgery. We studied phaco
      time, perioperative pain, visual outcome and intraoperative complications. The
      level of intraoperative pain was scored on a scale of 1-10, where 1 = no pain and
      10 = severe pain. RESULTS: 55 patients (91.6%) in the topical group and 54
      patients (94.7%) in the limbal group tolerated the procedure well, giving pain
      scores of 1-3, with no statistical difference. No patients in either group
      required supplemental anaesthesia and no intraoperative complications were
      recorded. No eyes had epithelial defects at the end of surgery or at
      postoperative check-ups. CONCLUSION: Limbal anaesthesia in cataract surgery is
      safe and the two anaesthesia techniques do not present differences in the degree
      of analgesia achieved.

PMID- 16445450
TI  - Slit-scan tomography evaluation of the anterior chamber and corneal
      configurations at different ages.
AB  - PURPOSE: To evaluate the aqueous humour and corneal volumes, their correlations
      to age, sex and refractive status, and their changes with age. METHODS: A total
      of 153 eyes of 153 healthy volunteers and 58 eyes of 58 patients planned for
      cataract surgery were examined with Orbscan II slit-scan tomography and the
      autorefractometer-keratometer. In 16 eyes of 16 volunteers, the same examinations
      were performed twice with a 4-year interval. Anterior chamber volumes were
      calculated with a 3-dimensional mapping method, corneal volumes were calculated,
      and multiple refraction and corneal/anterior chamber configuration variables were
      registered. RESULTS: The aqueous humour volume is inversely correlated to the age
      of the individual (r = - 0.22, p = 0.001), with an average decrease of 1.4 +/-
      2.6 microl per year on longitudinal follow-up (p = 0.042). Specifically, the
      posterior part of the anterior chamber undergoes a pronounced reduction in volume
      with time, whereas the volume of the anterior part increases slightly with time.
      Increasing steepness and peripheral thinning of the cornea (p = 0.034), and a
      reduction in corneal volume (p = 0.037) were also seen with increasing age. Males
      had less steeply curved corneas and higher aqueous humour volumes than females.
      CONCLUSION: The anterior segment of the eye undergoes continuous alterations with
      age, which differ significantly between the genders. These normal differences and
      alterations may be of importance in the planning of refractive procedures, and in
      the evaluation of disease processes.

PMID- 16445449
TI  - Monoamine receptors in human corneal epithelium and endothelium.
AB  - PURPOSE: Monoamine receptors are found throughout the body. Reports about the
      presence of monoamine receptors in the human cornea are inconsistent. METHODS:
      Immunohistochemistry, immunofluorescence and immunoblotting were used to localize
      monoamine receptor sites on human corneal epithelium and endothelium. RESULTS:
      Antibodies to alpha-1, beta-1 and beta-2 adrenergic receptors and to D1-like and
      5HT-7 receptors were bound in corneal epithelium. Antibodies to alpha-1, alpha
      2A, beta-1 and beta-2 adrenergic receptors and to 5HT-7 receptors were bound in
      corneal endothelium. CONCLUSIONS: Our data demonstrate the presence of several
      monoamine receptors in the human cornea. These receptors may play a role in the
      regulation of fluid transport or corneal homeostasis.

PMID- 16445451
TI  - One medial triangular Tutoplast sling as a frontalis suspension for adult
      myogenic blepharoptosis.
AB  - PURPOSE: The treatment of choice for medium to severe blepharoptosis with minimal
      or no levator function is frontalis suspension with a sling, using a rectangular
      or rhomboid sling placement technique. We describe the short-term, follow-up
      results of frontalis suspension surgery for adult myogenic blepharoptosis using
      Tutoplast, a commercially available fascia lata allograft. METHODS: We conducted
      a consecutive, interventional case study. All adult (>25 years of age) patients
      operated for non-traumatic myogenic ptosis during a 1-year period were included.
      All underwent frontalis suspension using one medial triangular Tutoplast sling.
      Success was judged according to lid position and complications. RESULTS:
      Successful surgical results were judged by lid level, lid symmetry and lid
      contour. During a mean follow-up of 9 months, the success rate was 91% in all
      three criteria and 100% in at least two out of three. No major complications were
      observed. The most prevalent minor complication was the need for lubrication
      treatment in 26% of the operated patients. CONCLUSION: The use of Tutoplast for
      frontalis suspension in cases of adult myogenic ptosis is safe and has a high
      success rate in the early postoperative period. Further large-scale studies are
      necessary to ascertain the longterm results and the applicability of this
      material to other indications.

PMID- 16445452
TI  - The locus of fixation in strabismic amblyopia changes with increasing effort of
      recognition as assessed by scanning laser ophthalmoscope.
AB  - PURPOSE: We performed a qualitative assessment of fixation behaviour in relation
      to the fovea in patients with strabismic amblyopia. METHODS: The fixation of 25
      patients with strabismic amblyopia was examined using a scanning laser
      ophthalmoscope (SLO). A digital frame grabber board was programmed to scan onto
      the patient's retina single solid black discs of 5, 10 and 15 degrees in diameter
      and Landolt Cs in different orientations and corresponding to a visual acuity
      (VA) of 0.01-0.2 in European decimals. The relative position of the fovea was
      video-recorded. Fifty video fields per second were plotted as x/y (fixational
      positions in relation to the fovea) and x/t (motion over time) graphs. RESULTS:
      Three main groups of patients were seen. Group 1 (n = 6), with a VA of < 0.1,
      showed a grossly eccentric and unstable locus of fixation independent of
      size/type of test stimulus used. Group 2 (n = 15), with VA of 0.1-0.8, initially
      used an eccentric retinal area for fixation that, however, shifted to the fovea
      with decreasing size and increasing detail of the target for fixation. Group 3 (n
      = 4), with VA of 0.3-0.8, had stable central fixation throughout. CONCLUSIONS: We
      speculate that the reduced VA associated with strabismic amblyopia is due to a
      defective motor control of fixation that can be modulated by recognitional
      effort.

PMID- 16445453
TI  - Caruncular lesions in Denmark 1978-2002: a histopathological study with
      correlation to clinical referral diagnosis.
AB  - PURPOSE: To carry out a retrospective clinicopathological evaluation of
      caruncular lesions. METHODS: Data were collected from all surgically removed and
      histopathologically evaluated caruncular lesions registered by Danish pathology
      departments during the 25-year period 1978-2002. RESULTS: A total of 574
      caruncular lesions were identified. The number of caruncular lesions increased
      significantly during the 25-year period. This was due to an increase in the
      number of benign lesions, whereas the number of premalignant and malignant
      lesions remained constant. A total of 550 (96%) of the lesions were benign.
      Naevus (n = 248, 43%) and papilloma (n = 131, 23%) were the most common
      neoplasms. Premalignant lesions (n = 10, 1.7%) were dominated by primary acquired
      melanosis (PAM) with atypia and epithelial dysplasia. Malignant lesions
      constituted a total of 14 neoplasms (2.4%), with basal cell carcinoma (n = 4,
      0.7%) and lymphoma (n = 4, 0.7%) being the most frequent. The preoperative
      clinical diagnosis was correct in 286 (50%) of cases. CONCLUSION: Caruncular
      lesions are predominately benign but the lesions are rare and diverse, making
      clinical diagnosis difficult. Referral of excised lesions for pathological
      examination is recommended.

PMID- 16445454
TI  - Differential diagnosis of anterior chamber cysts with ultrasound biomicroscopy:
      ciliary body medulloepithelioma.
AB  - PURPOSE: To describe a case with motile cyst in the anterior chamber in the right
      eye of a 7-year-old boy. METHODS: The right eye's visual acuity was 20/50.
      Intraocular pressure was 59 mmHg. Slit-lamp examination showed prominent rubeosis
      iridis and a grey-white mass floating freely in the anterior chamber. Ultrasound
      biomicroscopy revealed a cystic mass in the anterior chamber. A diagnostic
      cyclectomy with removal of the anterior chamber cyst was performed.
      Histopathology of the anterior chamber lesion showed an intact cyst composed of
      medullary epithelial cells. Medulloepithelioma with malignant criteria was
      diagnosed and the eye was enucleated. RESULTS: Pathology demonstrated an
      medulloepithelioma with a few mitotic figures and nuclear pleomorphisms within
      the ciliary body. The patient was followed for 8 months without any metastasis in
      the orbit or elsewhere. CONCLUSION: Intraocular medulloepithelioma is a rare
      embryonic benign or malignant neoplasm typically diagnosed in the first decade of
      life as a ciliary body mass. A dislodged, free-floating anterior chamber cyst
      associated with neovascular glaucoma is typical of medulloepithelioma in
      children. This unique presentation should be differentiated from congenital iris
      epithelial, post-traumatic, epithelial, parasitic and neoplastic cysts.
      Ultrasound biomicroscopy is useful for analysing the structure of the anterior
      segment mass. Ciliary body medulloepithelioma is characterized by echogenic mass
      heterogeneity and an irregular surface containing multiple cystic cavities. Lack
      of glial differentiation may predict a better clinical outcome in primary
      neuroectodermal brain tumours.

PMID- 16445455
TI  - Achiasmia and unilateral optic nerve hypoplasia in an otherwise healthy infant.
AB  - An 18-month-old white boy, observed by his parents at 1-2 months age to have poor
      visual attentiveness and nystagmus, underwent an ophthalmological evaluation. The
      patient also underwent unsedated 5-channel flash visual evoked potentials (VEP)
      and sedated electroretinogram (ERG) testing as well as magnetic resonance imaging
      (MRI) of the brain and orbits. The VEP in response to monocular stimulation
      demonstrated occipital asymmetry and was clearly suggestive of crossed asymmetry
      and also showed right optic nerve hypoplasia. The MRI and fundoscopic
      examinations supported the findings of achiasmia and probable optic nerve
      hypoplasia. The patient also had decreased Teller card visual acuity, nystagmus
      and a variable right esotropia. Neurological examination was normal. The
      ophthalmological and MRI findings in this 18-month-old male patient support the
      diagnosis of isolated non-decussating retinal-fugal fibre syndrome as well as
      hypoplasia of the optic nerve.

PMID- 16445456
TI  - Acute retrobulbar optic neuropathy due to rupture of an anterior communicating
      artery aneurysm.
AB  - PURPOSE: The vast majority of ruptured aneurysms of the anterior communicating
      artery typically present with subarachnoid haemorrhage. Isolated visual
      complaints are very uncommon in this setting. We present an unusual case of a
      patient with an acute retrobulbar optic neuropathy, secondary to a ruptured
      anterior communicating artery aneurysm. DESIGN: Observational case report.
      METHODS: A 29-year-old woman was assessed for an acute, isolated unilateral optic
      neuropathy of unknown origin. Although an initial encephalic MRI was believed to
      be normal, an underlying ruptured anterior communicating artery aneurysm was
      eventually diagnosed when the patient became stuporous because of intracranial
      bleeding. CONCLUSIONS: Occurrence of an acute retrobulbar optic neuropathy may be
      the initial isolated sign related to a ruptured anterior communicating artery
      aneurysm, prompting an appropriate neuroradiological assessment.

PMID- 16445457
TI  - Optical coherence tomography of a giant, traumatic tear in the retinal pigment
      epithelium.

PMID- 16445458
TI  - Comparison of the efficacy of olopatadine hydrochloride 0.1% ophthalmic solution
      and artificial tears in seasonal allergic conjunctivitis.

PMID- 16445459
TI  - Should patients choose their own eyedrops?

PMID- 16445460
TI  - Frequency and predicting factors of surgical complications in cataract surgery
      performed under topical anaesthesia.

PMID- 16445462
TI  - Duration of facedown positioning after macular hole surgery: a comparison between
      1 week and 3 days.

PMID- 16445463
TI  - The presence of Propionibacterium spp. in the vitreous fluid of uveitis patients
      with sarcoidosis.

PMID- 16445475
TI  - Patients with severe mental illness: a most difficult-to-treat patient
      population. Proceedings of a conference on clinical and social psychiatry, 23-27
      September 2003, Zurich, Switzerland.

PMID- 16445476
TI  - Psychiatric services for people with severe mental illness across western Europe:
      what can be generalized from current knowledge about differences in provision,
      costs and outcomes of mental health care?
AB  - OBJECTIVE: To report recent findings regarding differences in the provision, cost
      and outcomes of mental health care in Europe, and to examine to what extent these
      studies can provide a basis for improvement of mental health services and use of
      findings across countries. METHOD: Findings from a number of studies describing
      mental health care in different European countries and comparing provision of
      care across countries are reported. RESULTS: The development of systems of mental
      health care in western Europe is characterized by a common trend towards
      deinstitutionalization, less in-patient treatment and improvement of community
      services. Variability between national mental healthcare systems is still
      substantial. At the individual patient level the variability of psychiatric
      service systems results in different patterns of service use and service costs.
      However, these differences are not reflected in outcome differences in a coherent
      way. CONCLUSION: It is conceivable that the principal targets of mental
      healthcare reform can be achieved along several pathways taking into account
      economic, political and sociocultural variation between countries. Differences
      between mental healthcare systems appear to affect service provision and costs.
      However, the impact of such differences on patient outcomes may be less marked.
      The empirical evidence is limited and further studies are required.

PMID- 16445477
TI  - Severe mental illness across cultures.
AB  - OBJECTIVE: International studies have shown that the outcome of illnesses like
      schizophrenia vary across cultures. The good outcome in developing countries
      depends upon a number of factors. METHOD: Using both primary and secondary
      sources, existing literature was reviewed. Using terms severe mental illness,
      culture and schizophrenia, Medline, Psychinfo and Embase were searched. Further
      searches were conducted using secondary searches. RESULTS: The impact of culture
      and its components on the individual and their families influences compliance,
      engagement with services and expectations of treatment. Cultures also impact upon
      identity and explanatory models of individuals. CONCLUSION: Severe mental illness
      is as likely to be affected by culture as other illnesses. Clinicians need to use
      multi-model assessment and management techniques.

PMID- 16445478
TI  - Heavy use of acute in-patient psychiatric services: the challenge to translate a
      utilization pattern into service provision.
AB  - OBJECTIVE: There is an inequality in resource utilization among acute psychiatric
      in-patients. About 20-30% of them absorb 60-80% of the total resources allocated
      to this form of treatment. This study intends to summarize findings related to
      heavy in-patient service use and to illustrate them by means of utilization data
      for acute psychiatric wards. METHOD: Longitudinal assessment of consecutive acute
      in-patients hospitalized for the first time. Analysis of individual utilization
      patterns by using latent class cluster analysis. RESULTS: Four groups with
      different utilization patterns were found all including heavy service users. In
      most cases heavy service use was temporary and could only be poorly predicted.
      CONCLUSION: Specific preventive interventions to contain heavy service use seem
      to be out of reach for the majority of high utilizing patients. However, services
      that have proven effective in reducing admissions to in-patient treatment and
      length of stay may nevertheless help to reduce heavy service use.

PMID- 16445479
TI  - De-constructing home-based care for mental illness: can one identify the
      effective ingredients?
AB  - OBJECTIVE: Home-based care for severe mental illness has been the focus of
      intense research over the last 30 years and has produced mixed results.
      Replications of Assertive Community Treatment (ACT) in Europe have consistently
      failed to find these differences and various explanations have been advanced for
      this. METHOD: Studies were compared in context of health care, and then
      identifying and rating the components of the differing teams rather than simply
      their designation. Cluster analysis was used for the identification of common
      service characteristics and regression analysis to test for correlation with
      reduction in hospitalization. RESULTS: The nature of the control service may
      significantly explain the international variation in results. Six regularly
      occurring features of experimental services were identified from the examination
      of the components - smaller case loads, regularly visiting at home, a high
      percentage of contacts at home, responsibility for health and social care,
      multidisciplinary teams and a psychiatrist integrated in the team. Two of these,
      regularly visiting at home and responsibility for health and social care, are
      significantly associated with a reduction in hospitalization. CONCLUSIONS: It is
      premature to define an optimal configuration for home based care services. The
      need for introducing differing components of such care will depend on what is
      currently available locally. Where regular home visiting to psychotic patients
      plus a broad service model incorporating health and social care objectives are
      provided, major reductions in in-patient care are not currently to be anticipated
      by service re-configurations.

PMID- 16445480
TI  - Intervention effects of supplying homeless individuals with permanent housing: a
      3-year prospective study.
AB  - OBJECTIVE: To describe the intervention effects of supplying homeless individuals
      with permanent housing. METHOD: In a prospective study, 109 male and 20 female
      homeless individuals were assessed at baseline and at 1- and 3-year follow-up
      concerning mental illness (SCID-I), psychopathology, global assessment of
      functioning, emotional lability and alcohol consumption. RESULTS: A high
      proportion (86%) of the individuals was able to maintain or improve stability of
      housing. Only minor changes were observed concerning mental illness and global
      functioning. Extensive alcohol consumption and high psychopathology increased the
      risk of losing the stable housing. CONCLUSION: The placement of homeless
      individuals in board and care homes or community housing after social counselling
      seems to be a necessary measure to remedy homelessness. However, supplying more
      permanent housing is not sufficient to decisively improve mental health status.

PMID- 16445481
TI  - The relationship between mental illness severity and stigma.
AB  - OBJECTIVE: To investigate influencing factors for lay perception of mental
      illness severity and their effects on the stigma of mental illness. METHOD:
      Selective review including attitude surveys assessing social distance towards
      different diagnostic labels, and attitudes towards treatment professions,
      treatment strategies, and psychopharmacotherapy. RESULTS: Lays differentiate in
      their attitudes towards people with mental illness according to the given
      diagnostic label, the involved treatment professions or institutions, the applied
      treatment methods, and the perceived psychosocial disability. CONCLUSION: Beside
      perceived treatment intensity and diagnostic label, the perception of social
      disability of mentally ill people accounts for a differentiated stigma. The
      question arises how anti-stigma-programmes can include the topic of social
      disability into their messages without risking to strengthen the stigma of mental
      illness.

PMID- 16445482
TI  - Determinants of quality of life in people with severe mental illness.
AB  - OBJECTIVE: The objective of this article was to review some methodological issues
      in this field and give an overview of empirical research findings with a special
      focus on factors associated with or affecting subjective quality of life in
      people with a severe mental illness. METHOD: A selective review of relevant
      scientific literature on quality of life in severe mental illness was conducted.
      RESULTS: Subjective quality of life in people with a severe mental illness is
      only to a lesser extent related to external life conditions. Major determinants
      are psychopathology, especially symptoms of depression and anxiety, and aspects
      of the social network. Personality related factors such as self-esteem are also
      influential. Comparative studies have further shown that patients in community
      care settings have a better subjective quality of life than patients in hospital
      settings. CONCLUSION: Efforts to improve subjective quality of life in people
      with severe mental illness should include a careful monitoring of depressive and
      anxiety symptoms, and pay particular attention to assessment of and interventions
      against unmet needs. Further, such interventions should stress a strengthening of
      the social support of the clients. It is also important to pay attention to
      mediators of changes in subjective quality of life such as self-esteem, mastery,
      autonomy, and self-efficacy.

PMID- 16445483
TI  - Do mental health professionals stigmatize their patients?
AB  - OBJECTIVE: Assessing stereotypes towards people with mental illness among mental
      health professionals, comparing their view to the Swiss general population and
      analysing the influence of demographic factors, profession and work place
      variables (type of ward, employment time and professional experience). METHOD:
      Conducting a representative telephone survey (n = 1073). Factor analysis was used
      to achieve one-dimensional scales, which were analysed by regression analysis.
      RESULTS: Most positive depictions were regarded as less characterizing people
      with mental illness, whereas most negative descriptions were viewed as more
      typing these people. Compared with the Swiss general population, mental health
      professionals have not consistently less negative or more positive stereotypes
      against mentally ill people. Of the 22 stereotypes five factors were detected:
      'social disturbance', 'dangerousness', 'normal healthy', 'skills' and 'sympathy'.
      Stereotypes about people with mental illness are influenced by the professional
      background and if at all only slightly affected by gender, age, ward type,
      participation rate of the hospital, weekly working hours or years of professional
      experience. CONCLUSION: Mental health professionals must improve their attitudes
      towards people with mental illness. Different ways, e.g. improving their
      professional education or their quality of professional contacts by regular
      supervision to prevent burn-out, are discussed.

PMID- 16445484
TI  - Family burden and social network in schizophrenia vs. physical diseases:
      preliminary results from an Italian national study.
AB  - OBJECTIVE: To compare burden and social network in families of patients with
      schizophrenia or physical diseases. METHOD: A total of 709 relatives of patients
      with schizophrenia and 646 relatives of patients with physical diseases were
      recruited in 169 specialized units located in 30 randomly selected Italian
      geographical areas. RESULTS: In both groups, the consequences of caregiving most
      frequently reported as present were constraints in social activities, negative
      effects on family life and a feeling of loss. Objective burden was similar in the
      two groups, while subjective burden was higher in schizophrenia. Social support
      was lower among relatives of patients with schizophrenia than among those of the
      other group. CONCLUSION: These results highlight the need to provide families of
      those with long-term diseases with supportive interventions, aiming to: i) manage
      relatives' psychological reactions to patient's illness; ii) provide information
      on patient's disease; iii) reinforce relatives' social network, especially in the
      case of schizophrenia.

PMID- 16445485
TI  - Severe mental illness in depression.
AB  - OBJECTIVE: The study aimed to evaluate the outcome from in-patient treatment in
      major depressive disorders (MDD) and its impact on the patients' 1 year outcome
      under the present routine care conditions. METHOD: The reported data stem from a
      multicentric follow-up study on the course and outcome of patients with MDD.
      Patients enrolled in the study had their first or multiple psychiatric
      hospitalization and fulfilled the ICD-10 criteria for a depressive disorder.
      During in-patient treatment patients were standardized assessed in 2-weekly
      intervals, with yearly follow-up evaluations after discharge. RESULTS: The
      analyses revealed that the elimination of depressive symptoms and a return to
      premorbid levels of functioning is a rarity in the in-patient treatment of MDD.
      Moreover, the analyses revealed that the achieved level of response during in
      patient treatment clearly determines the patients state 1 year after discharge
      from in-patient treatment. CONCLUSION: Considering that persisting depressive
      symptoms are associated with a range of unfavourable outcomes, the present data
      point to a serious problem in the treatment of MDD and the urgent need to further
      optimize antidepressive treatment strategies.

PMID- 16445486
TI  - The therapeutic relationship in psychiatric settings.
AB  - OBJECTIVE: To discuss the current climate of research on the therapeutic
      relationship (TR) in mainstream psychiatric settings. METHOD: Consideration of
      theoretical frameworks, quantitative and qualitative research methods, along with
      potentials for interventions. RESULTS: Most of the concepts and methods used to
      investigate the TR in conventional psychiatric settings have been imported from
      psychotherapy and, despite significant differences between the two, there is
      little specific research. A distinction is suggested between therapeutic
      relationships and patient-clinician interactions. Relationships predict outcome
      and may be assessed with operationalized methods. Specific communicative skills
      may be helpful in the treatment of particular illnesses. The feasibility and
      effectiveness of potential interventions in the TR have rarely been studied.
      CONCLUSION: Specific conceptual and methodological work is required to develop a
      better understanding of TRs in psychiatric settings. Further research should
      include intervention studies and might support a stronger emphasis on TRs in
      training and supervision.

PMID- 16445488
TI  - The Australian experience of deinstitutionalization: interaction of Australian
      culture with the development and reform of its mental health services.
AB  - OBJECTIVE: To describe the Australian experience of deinstitutionalization of the
      Australian National Mental Health Strategy in the context of the history of
      mental health services in Australia, and of Australian culture. METHOD: The
      development of Australian Mental Health Services is described with reference to
      developments in both psychiatric intervention research and Australian culture.
      The effects and achievements of national mental health reforms are described and
      critically examined. RESULTS: The relationship in Australia between the
      development of mental health services and the development of Australian society
      includes the stories of colonization, gold rush, suppression of indigenous
      peoples' rights, incarceration of mentally ill people, and incompatible state
      service systems. Mental health services required reform to provide consistent
      services and support for full citizenship and rights for such individuals who are
      still on the margins of society. Recent national developments in service models
      and service system research have been driven by the Australian National Mental
      Health Strategy. The translation of national policy into state/territory mental
      health service systems has led to a 'natural' experiment between states.
      Differing funding and implementation strategies between states have developed
      services with particular strengths and limitations. CONCLUSION: The effects of
      competition for limited resources between core mental health service delivery and
      the shift to a population-based public health approach (to prevention of mental
      illness and promotion of mental health), leaves our services vulnerable to doing
      neither particularly well. The recent loss of momentum of these reforms, due to
      failure of governments to continue to drive and fund them adequately, is causing
      the erosion of their considerable achievements.

PMID- 16445487
TI  - Early detection and treatment of schizophrenia: how early?
AB  - OBJECTIVE: Whereas early detection and therapy of schizophrenic psychoses until
      some time ago concentrated on frank schizophrenia, during the last years some
      centres have also started to treat patients even before a clear diagnosis could
      be established. This paper attempts to discuss if and when this is justified in
      the light of recent research. METHOD: Mini review of literature. RESULTS: The
      rationale for early detection and treatment of schizophrenia is based on several
      observations: diagnosis and treatment of schizophrenia are often seriously
      delayed. Consequences of the disease are severe already in the early undiagnosed
      phase of the disorder and early treatment seems to improve the course of the
      disease. It can therefore be stated quite safely that patients should be treated
      as early as possible. However, the question of how early has not been
      sufficiently answered up to now. CONCLUSION: We are at the moment in an ethical
      dilemma between either diagnosing and treating this disorder too late or too
      early. The only way and prerequisite for solving this dilemma is a more reliable
      identification of individuals at risk and the beginning disease process.

PMID- 16445489
TI  - Evaluating a community-based mental health service focusing on severe mental
      illness. The Verona experience.
AB  - OBJECTIVE: To describe the development of a community-based mental health
      service, the patterns of care provided by this new service established in 1978
      and its costs. METHOD: The South-Verona Psychiatric Case Register, the South
      Verona Outcome Project and studies designed to assess costs provided process and
      outcome data. RESULTS: This paper summarizes descriptive statistics as well as
      the results of some evaluative studies conducted over the last 25 years in
      Verona, Italy. It reports patterns of care provided over the years by this new,
      comprehensive community-based service, targeted to the severely mentally ill but
      available also to all other residents in the area who need mental health care.
      CONCLUSION: Developing community-based mental health care requires a series of
      coordinated actions that need to be pursued over a long period of time. Service
      evaluation, including costs assessment, is an important part of this exercise.

PMID- 16445490
TI  - Social psychiatry and public mental health: present situation and future
      objectives. Time for rethinking and renaissance?
AB  - OBJECTIVE: To describe the social psychiatric challenges of modern psychiatry in
      European societies in the light of recent psychiatric research evidence and to
      show how these challenges could be conceptualized. METHOD: Reviewing aggregate
      morbidity and mortality data from the WHO European Health for All Database, and
      summarizing consultations and fact-finding missions to many European countries
      during the authors engagement as WHO Regional Advisor for Mental health from 1998
      to 2004. RESULTS: Societal change in Europe is leading to stress and mental ill
      health for its populations. The consequence is a dramatic increase in burden due
      to mental illness and stress-related morbidity and mortality. CONCLUSION: A re
      thought and re-conceptualized social and societal psychiatry with focus on public
      mental health must have a renaissance. Innovative efforts are of crucial and
      imperative importance seeing mental health in the light of recent experience and
      science as probably the most important public health issue.

PMID- 16445491
TI  - The chronic psychiatric patient: problems, promises and perspectives, past,
      present and future.
AB  - OBJECTIVE: To present an overview of the issues involving the severely and
      chronically mentally ill over the past 50 years and summarize new research that
      may aid them. METHOD: To present the problems that have faced and will face this
      population, the promises that have been made about and to them, and assess how
      well we fulfilled our promises and handled the problems. RESULTS: We have made
      some but not enough progress in solving the problems facing the severely and
      chronic mentally ill in the past and at present, but the future holds more hope
      if recent solid, practical, economically feasible mental health services research
      is translated through policy and practice into better patient care. CONCLUSION:
      As pessimistic as we often are about the plight of the chronic mentally ill,
      their future can be better if recent research is implemented.

PMID- 16445492
TI  - Who decides what evidence is? Developing a multiple perspectives paradigm in
      mental health.
AB  - OBJECTIVE: To compare different perspectives on evidence in relation to mental
      health care. METHOD: The method and materials constitute a selective literature
      review comparing key elements of evidence-based medicine and evidence-based
      policy with perspectives on evidence from users, carers and professionals. The
      aim was to develop an argument concerning these comparisons. RESULTS: What
      constitutes evidence from the perspectives of different stakeholders is a field
      of contestation. CONCLUSION: It is timely for a multiple perspective paradigm on
      evidence in science to be developed and this paper initiates this process in
      relation to mental health care.

PMID- 16445493
TI  - Needs of people with severe mental illness.
AB  - OBJECTIVE: This study reviews conceptual and methodological issues of needs for
      care among people with severe mental illness (SMI) and presents data on their
      prevalence, correlates and consequences for mental health care. METHOD: Focus is
      on the definition of the concept of need as what people can benefit from and its
      measurement by means of two instruments, the Needs for Care Assessment (NCA) and
      the Camberwell Assessment of Needs (CAN). RESULTS: The prevalence of needs among
      patients with SMI varies between 4 and 10, which appears to be rather unrelated
      to gender, age or education, but not to severity of symptoms, diagnosis or
      treatment setting. Important is the perspective of the beholder: patient and
      professional differ significantly from each other in the assessment of number of
      needs and their adequate fulfillment. One of two to four needs are unmet, in
      particular in the area of psychological distress, daily activities, social
      contacts and psychotic symptoms. Prevalence of unmet needs seems to be related to
      the system of mental health care and to socioeconomic circumstances as well: the
      less integrated and continuous care and the poorer the life situation, the more
      unmet needs. CONCLUSION: Unmet needs are a strong predictor of less favourable
      health perceptions and a lower quality of life. Needs are to a certain extent
      changeable, and thus amenable by treatment or mental health interventions. The
      prevalence of (un)met needs should be an outcome criterion for the evaluation of
      mental health service systems and for cross-cultural comparison.

PMID- 16445494
TI  - Childhood molluscum contagiosum.

PMID- 16445495
TI  - Tinea capitis in eastern Nepal.
AB  - BACKGROUND: Tinea capitis is an increasing public health concern throughout the
      world. The clinical types and etiological agents vary from time to time and place
      to place. This study was undertaken to identify the etiological agents and to
      determine the clinico-etiological correlation of tinea capitis in eastern Nepal.
      METHODS: Sixty-nine clinically diagnosed cases of tinea capitis were enrolled in
      this study. Hair roots and skin scrapings were collected from each patient and
      subjected to microscopy and culture for identification of fungal hyphae and
      spores. RESULTS: Tinea capitis accounted for 4.6% of all dermatophyte infections:
      68.1% occurred in patients below the age of 11 years with a male to female ratio
      of 1 : 1.9. "Gray patch" was the most common clinical type (52.2%), followed by
      "black dot" (17.4%), seborrhoeic dermatitis (13%), alopecia areata (11.6%) and
      pustular (4.3%). Direct microscopy of hair was positive in 62.3% of patients.
      Culture positivity was found in 56.7% of patients. Common isolated organisms were
      Trichophyton violaceum (48.71%), T. mentagrophytes (15.38%), T. tonsurans
      (12.82%), Microsporum canis (7.69%), T. rubrum and M. gypseum (5.12% each), and
      M. audouinii and M. nanum (2.56% each). CONCLUSIONS: Trichophyton violaceum was
      the most common pathogen of tinea capitis. The clinical manifestations were
      variable and "gray patch" was the most common clinical presentation in this part
      of the world.

PMID- 16445496
TI  - Epidemiology of pemphigus in south-western Iran: a 10-year retrospective study
      (1991-2000).
AB  - BACKGROUND: Pemphigus is a disease demonstrating an uneven geographic
      distribution. This is the first epidemiologic study of pemphigus in Iran.
      METHODS: Data were collected from the files of all newly registered patients with
      pemphigus at the sole dermatologic referral center for south-western Iran located
      in the city of Shiraz, during the period 1991-2000. The data were analyzed with
      regard to age, sex, subtypes of pemphigus, clinical presentation, and season of
      onset. RESULTS: The results showed that the mean incidence of the disease for the
      overall population in Shiraz was 0.67/10(5)/year. The male to female ratio was 1
      : 1.33. The mean age at onset of the disease was 38 years (range, 12-93 years).
      The disease was most common in the third to fifth decades (62.1% of the overall
      patients). Pemphigus vulgaris was the most commonly encountered type, followed by
      pemphigus foliaceus (87.7% and 9%, respectively). The first manifestations of the
      illness most often occurred during winter (30.8% of the patients). CONCLUSIONS:
      The results reveal a high incidence of pemphigus vulgaris in south-western Iran
      compared with that encountered in other countries. Our patients also had a
      relatively young age at onset and a female predominance.

PMID- 16445497
TI  - Efficacy of autologous transplantation of noncultured epidermal suspension in two
      different dilutions in the treatment of vitiligo.
AB  - BACKGROUND: Previous reports have shown the effectiveness of a basal layer cell
      suspension in the treatment of stable vitiligo; however, there has been no
      mention in the literature until now of the optimal number of melanocytes required
      in an autologous noncultured epidermal suspension for transplantation to obtain
      early and acceptable results. METHODS: In this randomized prospective study, we
      compared the efficacy of two different dilutions to determine the optimum density
      of melanocytes required for transplantation to achieve early and cosmetically
      acceptable results. We enrolled 20 patients with stable vitiligo with a body
      surface area involvement of< 10%. RESULTS: Fifty per cent of patients in Group A
      (where the recipient area transplanted was approximately three times the size of
      the donor area, and the density of melanocytes transplanted per square millimeter
      was approximately 231.60+/- 27.03) showed marked (> 75%), 20% moderate, 10% mild,
      and 20% minimal repigmentation (or no response). In Group B (where the recipient
      area was increased to five-fold the donor area), none of the patients showed
      marked, 10% showed moderate, 20% showed mild, and 70% showed either minimal or no
      repigmentation. The density of melanocytes transplanted in this group was
      154.90+/- 27.65/mm(2). The extent of repigmentation was significantly greater (P<
      0.05) in Group A than in Group B, and the density of melanocytes in the
      suspension was also significantly greater (P< 0.01) in Group A than in Group B.
      CONCLUSION: We contend that the minimum number of melanocytes required to produce
      satisfactory repigmentation is probably in the range of 210-250/mm(2).

PMID- 16445498
TI  - Correlates of health-related quality of life in women with severe facial
      blemishes.
AB  - BACKGROUND: Facial appearance plays a large role in self-perception and
      interaction with others. Visible facial skin lesions are a common condition.
      Purpose This study assessed factors associated with health-related quality of
      life (HRQOL) in women with visible facial skin lesions. METHODS: The study
      included 73 women with one or more of the following conditions: acne, dermatosis
      papulosis, hypopigmentation, lentigenes, melasma, rosacea, vascular
      proliferations and other facial scars. The Skindex-16 was used as a measure of
      HRQOL. Fear of negative evaluation (FNE) was assessed to determine whether self
      perception characteristics relate to HRQOL. RESULTS: There were strong
      correlations in both bivariate and multivariate analyses among increased FNE,
      heightened perception of QOL without the facial condition and lower overall HRQOL
      (P< 0.05 and P< 0.01, respectively). There were no differences in HRQOL by type
      of facial condition, as well as no effects of the area covered by the condition
      on HRQOL. Interestingly, women not using foundations represented only 10% of the
      study population and had better HRQOL than women who did use foundations.
      CONCLUSIONS: Severe facial blemishes of any cause have a significant impact on
      women's QOL, and the effect of these lesions is mediated in part by psychological
      characteristics related to self-perception and self-presentation.

PMID- 16445499
TI  - Leishmaniasis recidiva cutis due to Leishmania (Viannia) panamensis in
      subtropical Ecuador: isoenzymatic characterization.
AB  - BACKGROUND: Information regarding leishmaniasis recidiva cutis (LRC), a clinical
      variant of cutaneous leishmaniasis, in the New World is scarce. LRC is
      characterized by slowly progressing lesion(s) that appear after a variable period
      of time, from months to years, in or around the scar of an apparently clinically
      healed sore. PATIENTS AND METHODS: Six patients are reported who presented with
      crusted, papular lesions located on the edge of a healed scar, with a mean of
      18.2 months of slowly progressive evolution. The isolated strains of Leishmania
      parasites were characterized by enzyme electrophoresis. Eleven enzyme systems
      were assayed. Skin biopsies from the active border of the lesions were taken for
      histopathology. RESULTS: Tissue sections showed a granulomatous,
      lymphohistiocytic, dermal infiltrate containing Langhans' giant cells. The
      anamnestic data, together with the clinical and histopathologic findings, support
      the diagnosis of LRC. The isoenzyme profile of Leishmania parasites isolated from
      five of the six patients identified them as Leishmania (Viannia) panamensis.
      CONCLUSIONS: These findings are the first reported evidence of LRC within the
      clinical spectrum of American tegumentary leishmaniasis in Ecuador, and of its
      causative agent. The existence of LRC has future implications for both disease
      treatment and vaccine development.

PMID- 16445500
TI  - Primary cutaneous coccidiodomycosis: case report and review of the literature.
AB  - BACKGROUND: Coccidiodomycosis is a systemic infection caused by Coccidioides
      immitis, a dimorphic fungus endemic in the south of the USA and the north of
      Mexico. The disease usually affects the lungs. Primary cutaneous infection is
      extremely rare. We present a report of a patient with primary cutaneous infection
      located on the nose. To our knowledge, such a presentation has never previously
      been reported in the literature. OBSERVATIONS: The patient had a 3-cm-diameter
      elevated nodule with a verrucous aspect located on the tip of her nose. The
      histopathologic features of the lesion were consistent with coccidioidomycosis.
      CONCLUSIONS: To our knowledge, this is the first report of primary cutaneous
      coccidioidomycosis located on the tip of nose.

PMID- 16445501
TI  - Cutaneous protothecosis: report of a third Brazilian case.
AB  - The present report describes a case of cutaneous protothecosis caused by
      Prototheca wickerhamii in a nonimmunocompromised Brazilian female. Dermatological
      examination revealed a 15-cm diffusely infiltrated eczema-like plaque recovered
      with many pustule-like lesions on the right forearm. We emphasize the mycological
      and pathological aspects of this infection that can lead to misdiagnosis. The
      patient was successfully treated with itraconazole.

PMID- 16445502
TI  - Hairy elbows syndrome.

PMID- 16445503
TI  - Psoriasiform cutaneous leishmaniasis.

PMID- 16445505
TI  - A new gastrointestinal finding in Proteus syndrome: report of a case of multiple
      colonic hemangiomas.
AB  - A patient with Proteus syndrome presented with lower gastrointestinal bleeding
      due to multiple colonic hemangiomas, a finding which has not been described
      previously in this syndrome. The patient was a 20-year-old man with features
      fulfilling the diagnostic criteria for Proteus syndrome. He fulfilled both
      general criteria (mosaic distribution of the lesions, progressive course and
      sporadic occurrence) and specific criteria (including epidermal nevus,
      disproportionate overgrowth of limbs and vascular malformations). Fiberoptic
      colonoscopy revealed multiple hemangiomas, 0.5-1 cm in diameter, on the left side
      of the colon. Some gastrointestinal complications have been reported in patients
      with Proteus syndrome, including rectal polyps, colonic lipomatosis, atrophy of
      the intestinal villi and intestinal affection with fatty wall thickening but, as
      far as we are aware, colonic hemangiomas have not previously been reported in
      this syndrome.

PMID- 16445504
TI  - Neonatal eosinophilic pustulosis.
AB  - A pre-term, 7-week-old male infant presented with a recurrent pustular eruption
      involving his face and scalp with associated peripheral blood eosinophilia. Skin
      biopsy revealed spongiosis with numerous dermal and epidermal eosinophils without
      predominant follicular involvement. Immunohistology showed deposition of
      eosinophil granule major basic protein and eosinophil derived neurotoxin in the
      dermis and epidermis. He responded to conservative management. We discuss the
      differential diagnosis of neonatal eosinophilic pustular eruptions and suggest
      the term 'neonatal eosinophilic pustulosis' to best describe our case.

PMID- 16445506
TI  - Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two disease
      entities in the same patient: case report and review of the literature.
AB  - BACKGROUND: Much controversy has existed with regard to the relationship between
      Kimura's disease and angiolymphoid hyperplasia with eosinophilia. They were
      initially thought to represent the same disease spectrum, but it has now been
      widely accepted that they are two separate disease entities. To our knowledge,
      there have been no reports to date describing a case of both Kimura's disease and
      angiolymphoid hyperplasia with eosinophilia coexisting in the same patient.
      METHODS: We describe a patient presenting initially with a right postauricular
      subcutaneous swelling and subsequently developing multiple erythematous facial
      papules and nodules. The medical literature is reviewed. RESULTS: Clinical
      features of the right postauricular subcutaneous swelling and multiple
      erythematous facial papules/nodules suggest Kimura's disease in the former and
      angiolymphoid hyperplasia with eosinophilia in the latter. Histopathological
      examinations of these lesions helped to confirm the diagnosis of Kimura's disease
      and angiolymphoid hyperplasia with eosinophilia, respectively. CONCLUSIONS:
      Kimura's disease and angiolymphoid hyperplasia with eosinophilia can coexist in
      the same patient. Coexistence of the two types of lesions in one patient may also
      be considered evidence that Kimura's disease and angiolymphoid hyperplasia with
      eosinophilia form a spectrum in one disease.

PMID- 16445507
TI  - Eccrine porocarcinoma arising in two African American patients: distinct
      presentations both treated with Mohs micrographic surgery.
AB  - Abstract Background Eccrine porocarcinoma (EPC) is a rare, malignant adnexal
      tumor that has been reported only three times specifically in African American
      individuals. Diagnosis and treatment of EPC is important, given the 20% local
      recurrence and regional metastatic rates. However, no standard of care has been
      developed to guide effective treatment. Methods We report two distinct clinical
      presentations of EPC, both in African Americans, and discuss a review of the
      literature. Results The neoplasms were successfully removed from both patients by
      Mohs micrographic surgery. Conclusions These two cases illustrate that EPC can
      have a variety of presentations and can occur in African Americans. Although
      there is no standard of care for treating EPC, Mohs is becoming a common
      technique of removing these lesions.

PMID- 16445508
TI  - Successful treatment of vulvar Bowen's disease with topical imiquimod 5% cream.

PMID- 16445509
TI  - Clinical efficacy and safety of oral terbinafine in fungal mycetoma.
AB  - OBJECTIVES: An open-label study was performed to assess the efficacy and safety
      of terbinafine in the treatment of eumycetoma. METHODS: Single-center, open-label
      study, including 27 patients with signs and symptoms of eumycetoma which had
      developed within 5 years and was confirmed by mycological examination. The
      intention-to-treat population (n=23) received 500 mg of terbinafine bid for 24-48
      weeks. Efficacy evaluations included clinical signs and symptoms (e.g. sinuses
      open or closed, degree of tumefaction, and emission of grains either present or
      absent); mycological examinations from Week 24 onwards; and investigators'
      overall assessment of efficacy (cure, improved since baseline, unchanged since
      baseline, or deterioration since baseline). Safety evaluations included
      monitoring of adverse events, laboratory assessments, vital signs and physical
      examinations. RESULTS: Good clinical improvement was seen in patients who
      completed the study (n=20). Tumefaction was absent or improved in 80% of
      patients; sinuses were closed in 50% of patients, and grain emissions were absent
      in 65% of patients. Of the 16 patients who had repeat mycological assessment,
      four (25%) were mycologically cured. In the investigators' overall opinion at the
      end of the study, five (25%) were cured and 11 (55%) were clinically improved.
      The majority of adverse events reported were mild to moderate, and consistent
      with the known tolerability profile of terbinafine. CONCLUSION: High-dose
      terbinafine (1,000 mg/day) is well tolerated and clinically effective in patients
      with eumycetoma, a difficult-to-treat subcutaneous mycoses.

PMID- 16445510
TI  - Leg ulcer in a patient associated with hydroxyurea therapy.
AB  - Hydroxyurea is a hydroxylated derivate of urea commonly used in the treatment of
      various hematologic disorders. Cutaneous side-effects such as alopecia, diffuse
      hyperpigmentation, scaling, poikiloderma, atrophy of the skin and subcutaneous
      tissues or nail changes can develop after long-term treatment with hydroxyurea.
      Painful leg ulcers in association with hydroxyurea have only rarely been
      reported. We present a report of a 52-year-old patient with essential
      thrombocythemia suffering from painful leg ulcers 3 years after starting therapy
      with hydroxyurea. We decided to treat the leg ulcers following a modern phase
      adapted wound-healing strategy and continued hydroxyurea therapy until complete
      healing of the ulcers. In conclusion, cutaneous ulceration of the leg is one
      adverse effect in patients with essential thrombocythemia during hydroxyurea
      therapy. Healing does not necessarily require discontinuation of the drug.
      Therefore, therapists should first optimize a conservative and systematic wound
      healing strategy. If these interventions fail, discontinuation of hydroxyurea
      therapy is advisable.

PMID- 16445511
TI  - Skin disease in mummies.

PMID- 16445512
TI  - Lepra vaccine: misinterpreted myth.

PMID- 16445513
TI  - Recovery of anaerobic bacteria from a case of dissecting cellulitis.

PMID- 16445514
TI  - Papular sarcoidosis limited to the knees: a clue for systemic sarcoidosis.

PMID- 16445515
TI  - Familial pemphigus vulgaris: two siblings with unusual localized variant.

PMID- 16445516
TI  - Nail findings in pemphigus vulgaris.

PMID- 16445519
TI  - Effects of KUR-1246, a selective uterine relaxant, on transplacental passage and
      transmigration to milk.
AB  - AIM: To evaluate the safety of KUR-1246 as a tocolytic agent, we determined the
      effects of its constant infusion on efficacy, transplacental passage, and
      transmigration to milk in pregnant or puerperal animals and compared them to the
      effects of ritodrine hydrochloride. METHODS: A balloon method was used to
      evaluate the inhibitory effects of KUR-1246 constant infusion on spontaneous
      uterine motility in pregnant rats. We also measured transplacental passage and
      transmigration to milk of KUR-1246 in pregnant and/or puerperal animals. KUR-1246
      and ritodrine hydrochloride concentrations were quantified using a liquid
      chromatography-tandem mass spectrometry method. RESULTS: Constant infusion of KUR
      1246 and ritodrine hydrochloride clearly inhibited spontaneous uterine motility
      in vivo. The ED50 value for KUR-1246 was 1.1 mg/kg/min, a potency which was
      approximately 40-fold greater than that of ritodrine hydrochloride.
      Transplacental passage (proportions of fetal plasma/maternal plasma) of KUR-1246
      in pregnant rats and/or guinea pigs were approximately one-half to one-third of
      that of ritodrine hydrochloride. Transmigration of KUR-1246 to milk in puerperal
      rats disappeared by 48 h after injection. CONCLUSIONS: KUR-1246 is a promising
      drug for the treatment of preterm labor in obstetric practice because it is as
      efficacious as currently used agents yet less likely to produce direct effects on
      the fetus.

PMID- 16445520
TI  - Changes in plasma levels of hepatocyte growth factor and its associated factors
      during pregnancy.
AB  - AIM: Hepatocyte growth factor (HGF) was originally identified as a factor that
      stimulates the mitogenesis of hepatocyte, and also plays a role in maintaining
      pregnancy. We conducted this study to evaluate the changes in plasma
      concentrations of HGF and its associated factors during normal pregnancy.
      METHODS: Blood specimens were obtained from 14 healthy non-pregnant and 175
      healthy pregnant and post-partum women (189 women in all). The women's plasma
      concentrations of total HGF, active HGF, active HGF activator (HGFA), HGF
      activator inhibitor type 1 (HAI-1) and HGF activator inhibitor type 2 (HAI-2)
      were determined by enzyme-linked immunosorbent assay. RESULTS: The levels of
      active HGF and HGF activator were significantly lower in pregnant women compared
      with those of non-pregnant women. The level of plasma HAI-1 significantly
      increased as pregnancy progressed, while it fell post-partum. Also, there were no
      differences in the concentrations of total HGF and HAI-2 in non-pregnant and
      pregnant women. CONCLUSION: A high concentration of HAI-1 during pregnancy may
      decrease the plasma level of active HGFA. This may in turn inhibit the activation
      of the precursor form of HGF, leading to a decrease in the level of plasma active
      HGF.

PMID- 16445521
TI  - Influence of alpha-tumor necrosis factor and beta-interleukin-1 on production of
      angiogenetic factors and thymidine phosphorylase activity in immortalized human
      decidual fibroblasts in vitro.
AB  - AIM: The aim of the present study was to investigate regulatory mechanisms of
      angiogenesis in the decidua using immortalized human decidual fibroblasts.
      METHODS: A sample of decidual fibroblasts was taken from a woman in early
      pregnancy. A cell line, DE-1, was established by infecting the decidual
      fibroblasts with the simian virus 40 large T antigen. Using this cell line, the
      ability to produce vascular endothelial growth factor (VEGF), basic fibroblast
      growth factor (bFGF), beta-transforming growth factor (TGF-beta), and thymidine
      phosphorylase (TP) activity was investigated using immunohistochemistry, and the
      influences of beta-interleukin-1 (IL-1beta) and alpha-tumor necrosis factor (TNF
      alpha) on these angiogenetic factors was investigated using enzyme-linked
      immunosorbent assays. Furthermore, the effects of TNF-alpha on proliferative
      capacity and apoptosis induction in DE-1 were studied. RESULTS: It was
      demonstrated that DE-1 produced all of these angiogenetic factors. The production
      of VEGF, bFGF and TGF-beta respectively was enhanced by both IL-1beta and TNF
      alpha. TP activity was increased by TNF-alpha, but no increase was observed as a
      result of IL-1beta. It was shown that TNF-alpha suppressed the proliferation of
      DE-1 cells and significantly increased the percentage of apoptotic cells.
      CONCLUSION: It is suggested that IL-1beta and TNF-alpha stimulate decidual
      fibroblasts to up-regulate angiogenesis in the human decidua.

PMID- 16445522
TI  - Natural nutrient mixture effectively reduces collagen matrix contraction driven
      by human uterine smooth muscle cells.
AB  - AIM: Abnormal uterine myometrial contractility causes preterm delivery,
      contributing to perinatal morbidity and mortality. Disturbances in hormonal
      regulation and inflammation-related processes have been attributed a role in the
      pathophysiological mechanisms of uterine contractility. We investigated the
      effects of natural nutrients on uterine tissue contractility in vitro. METHODS:
      We used an in vitro model of collagen I gel contraction driven by embedded
      cultured human uterine smooth muscle cells (SMC). The effects of tested compounds
      were evaluated using their capacity to affect gel contraction (measured by
      reduction in gel area during 24-h incubation in serum free medium). Cellular
      expression of matrix metalloproteinases (MMP) was followed by gel zymography.
      RESULTS: Collagen gel contraction driven by uterine SMC was significantly
      stimulated by potassium chloride, pituitary hormone oxytocin and by inflammatory
      cytokine alpha-tumor necrosis factor (TNF-alpha). Accelerated gel contraction was
      accompanied by elevated secretion of MMP-2 and MMP-9 into cell culture media.
      Among a variety of purified bioflavonoids and polyphenol-enriched plant extracts
      tested for their ability to counteract uterine SMC-dependent collagen gel
      contraction, the strongest effects were demonstrated by epigallocatechin gallate
      and green tea leaf extract, respectively. The addition of ascorbic acid and the
      amino acids lysine, arginine, cysteine and proline to green tea extract further
      increased its effectiveness. A reduction in gel contraction correlated with
      decreased MMP expression. CONCLUSION: Based on these findings, we found that
      nutrients can effectively counteract uterine myometrial contraction and MMP
      activity in vitro, suggesting that pathophysiological mechanisms of abnormal
      uterine myometrial contractility can be counteracted by a combination of
      naturally occurring nutrients. These mechanisms might involve extracellular
      matrix remodeling.

PMID- 16445523
TI  - Total peroxyl radical-trapping ability and anti-oxidant vitamins of the umbilical
      venous plasma and the placenta in pre-eclampsia.
AB  - AIM: Our purpose was to investigate lipid peroxide levels, total peroxyl radical
      trapping anti-oxidative parameter (TRAP) values, and anti-oxidant vitamin levels
      in umbilical venous plasma and placental tissues, and to evaluate their roles in
      the pathophysiology of pre-eclampsia. METHODS: Samples of umbilical venous plasma
      and placental tissue homogenates were obtained from 23 normal and 18 pre
      eclamptic women at between 33 and 40 weeks' gestation. The enzyme-linked
      immunosorbent assay method was used to assay alpha-tumor necrosis factor (TNF
      alpha), and lipid peroxide levels were measured by thiobarbituric acid reaction.
      The TRAP values were measured using the modified Wayner's method. Ascorbic acid,
      retinol alpha-tocopherol and gamma-tocopherol were measured by high performance
      liquid chromatography. RESULTS: Levels of TNF-alpha in placental tissue
      homogenates of women with pre-eclampsia were significantly higher than those of
      women with normal pregnancy (21.4 +/- 3.39 v. 10.3 +/- 1.06 pg/mL, P < 0.05).
      Lipid peroxide levels in umbilical venous plasma and placental tissue homogenates
      of women with pre-eclampsia were significantly higher than those of women with
      normal pregnancy (10.3 +/- 1.1 v. 5.85 +/- 0.53, P < 0.01, 5.14 +/- 0.40 v. 3.99
      +/- 0.33 nmol/mg protein, P < 0.05, respectively). The TRAP values in umbilical
      venous plasma and placental tissue homogenates of women with pre-eclampsia were
      significantly lower than those of women with normal pregnancy (0.39 +/- 0.02 v.
      0.45 +/- 0.02, P < 0.05, 0.27 +/- 0.02 v. 0.34 +/- 0.03 mM, P < 0.05,
      respectively). Ascorbic acid levels in umbilical venous plasma and placental
      tissue homogenates of women with pre-eclampsia were significantly lower than
      those of women with normal pregnancy (325.4 +/- 50.4 v. 543 +/- 73.8, P < 0.05,
      219.0 +/- 21.0 v. 333.3 +/- 32.6 nmol/mL, P < 0.05, respectively). CONCLUSIONS:
      The above results suggest that increased oxidative stress in the placenta is
      involved in the pathophysiology of pre-eclampsia, and ascorbic acid may act as an
      important preventative factor in the development of pre-eclampsia.

PMID- 16445524
TI  - Real-time 3-D echocardiographic evaluation of the fetal heart using instantaneous
      volume-rendered display.
AB  - AIM: Using new real-time 3-D fetal echocardiography with instantaneous volume
      rendered display, we evaluated the heart anatomy of a number of normal fetuses
      during pregnancy. METHODS: Eighteen normal fetuses in 17 pregnancies (16
      singletons and one twin) at 18-38 weeks' gestation were studied using a
      transabdominal real-time 3-D ultrasound machine. This machine proved capable of
      providing continuous 3-D sonographic images every 0.05 and 0.035 s without the
      need for an external workstation or other additional, costly equipment. For each
      patient, the fetal heart was first monitored using conventional 2-D
      echocardiography and was monitored again within 10 min using real-time 3-D
      echocardiography. RESULTS: Consecutive real-time 3-D images showing a four
      chamber view, long-axis view, short-axis view, and right ventricular outflow
      tract view were obtained in 100%, 66.6%, 38.8%, and 22.2% of fetuses in the
      study, respectively. Morphological changes to each atrium or ventricle could be
      observed clearly and in detail throughout the cardiac cycle. The opening and
      closing of each valve were clearly visible. Moreover, these observations could be
      made from any direction. CONCLUSIONS: Real-time 3-D echocardiography provides a
      novel means for evaluation of the fetal heart in 3-D in real time in the second
      and third trimester of pregnancy. Real-time 3-D echocardiography may be an
      important modality in future fetal cardiac research and in evaluation of
      congenital heart disease in the fetus.

PMID- 16445525
TI  - Giant hemangioma of the fetal neck, mimicking a teratoma.
AB  - We present a case involving a giant hemangioma of the fetal neck, prenatal
      diagnosis of which was a teratoma. A 32-year-old pregnant woman was referred to
      our hospital at 31 weeks' gestation owing to a giant solid mass of the fetal neck
      and excessive amniotic fluid. The mass seemed to be occupying the neck almost
      entirely, extending to the nasopharyngeal cavity, the mandible, the surface of
      the left orbit and the left shoulder. Based on sonographic and magnetic resonance
      imaging (MRI) findings, diagnosis of a giant teratoma was made. Cesarean section
      was performed at 35.5 weeks' gestation, and a female infant weighing 2826 g was
      delivered. Purpurae were observed on the neck of the infant, and the tumor turned
      out to be a hemangioma. Postnatal MRI findings, in which the tumor's signal
      intensity differed from that of the prenatal findings, were quite compatible with
      the diagnosis of a typical hemangioma. Laser and corticosteroid treatment
      successfully decreased the volume of the mass. Although it may not always be
      possible to make a prenatal differential diagnosis between a hemangioma and a
      teratoma in the neck of the fetus, serial ultrasound and MRI examination are
      mandatory to evaluate the prognosis and to plan suitable treatment. Moreover,
      possible postnatal changes to the tumor characteristics have to be taken into
      consideration when evaluating the findings of prenatal diagnostic imaging.

PMID- 16445526
TI  - Complications and myoma recurrence after laparoscopic uterine artery occlusion
      for symptomatic myomas.
AB  - AIM: To determine the frequency and severity of complications and the recurrence
      of fibroids as a result of laparoscopic occlusion of the uterine artery (LOUA) in
      women with symptomatic fibroids. METHODS: One hundred and fourteen women with
      symptomatic fibroids were treated using ultrasonically activated shears, clips or
      electrosurgery. A retrospective evaluation of the complications and recurrence
      rate was carried out. For each patient, the analysis took place at least 3 months
      after the procedure was performed. Each complication was categorized using the
      complication classifications developed by the Czech Society of Gynecologic
      Endoscopy and a modified set of the classifications of the American College of
      Obstetricians and Gynecologists. All adverse events that occurred during the
      follow-up period were included, in addition to those that occurred after the 3
      months minimum interval. RESULTS: A total of eight women (7.1%, 95% confidence
      intervals [CI], 3.3-14.4) experienced complications; one of these women had two
      complications, resulting in a total of nine adverse events. There were no
      intraoperative complications and no permanent injuries. Two women required
      supracervical hysterectomy and myomectomy, respectively, as a result of fibroid
      necrosis. One patient had an undiagnosed endometrial stromal sarcoma after 12
      months of LOUA. The rate of fibroid recurrence was 9.0% (10 patients). The
      recurrence-free survival interval rate (no clinical failure, no recurrence) at
      23.6 months (median) follow-up was 88.3% (CI 84.9-93.5). CONCLUSION: The rate of
      complications and fibroid recurrence was low in patients undergoing LOUA.

PMID- 16445527
TI  - Is there a correlation between vaginal chlamydia infection and cervical smear
      abnormalities? A community-based study in the Al-Ain district, United Arab
      Emirates.
AB  - AIM: The purpose of this study was to determine the correlation between vaginal
      chlamydia infection and cervical abnormalities. The data on the prevalence of
      chlamydia infection and cervical abnormalities have been presented elsewhere and
      in this article we provide the results of a correlation analysis. METHODS: In
      this cross-sectional, community-based survey, women attending primary and
      secondary care in the Al-Ain medical district, United Arab Emirates, were offered
      cervical screening using the Papanicolaou smear, and chlamydia testing. A total
      of 793 women underwent cervical screening and 728 were tested for chlamydia. A
      commercially available kit was used to determine the prevalence of chlamydia. The
      correlation between cervical abnormalities and chlamydia infection was tested
      using the chi-squared test or Fisher's exact test, as appropriate. RESULTS: The
      prevalence of abnormal smears was 1.51% (95% confidence interval [CI], 0.66-2.4).
      Twelve subjects had abnormal smears, including smears showing atypical squamous
      cells of undetermined significance. The prevalence of chlamydia infection in this
      population was 2.5% (95% CI, 1.2-3.3). Statistical analysis showed no association
      (chi2 0.6, P = 0.4) between the prevalence of chlamydia infection and cervical
      abnormalities. CONCLUSION: Although there have been earlier reports of an
      association between vaginal chlamydia and cervical abnormalities, our study does
      not provide evidence to support this association.

PMID- 16445528
TI  - Intrapartum late deceleration develops more frequently in pre-eclamptic women
      with severe proteinuria.
AB  - AIM: Our purpose was to investigate the effect of proteinuria associated with pre
      eclampsia on intrapartum fetal heart rate patterns. METHODS: A retrospective
      study was performed involving 79 pregnant women with pre-eclampsia and 19
      pregnant women with gestational hypertension (GH). Pre-eclampsia was then
      classified into two groups according to the degree of proteinuria (> or = or < 3
      + dipstick), which was classified as severe urinary protein (UP; n = 35) and mild
      UP (n = 44) at delivery. Intrapartum fetal heart rate (FHR) monitoring was
      classified as either no deceleration, moderate variable deceleration, severe
      variable deceleration (sVD), prolonged deceleration (PD), occasional deceleration
      or recurrent late deceleration (rLD). We evaluated the prevalence of non
      reassuring FHR (sVD, PD or rLD), the prevalence of intrauterine growth
      restriction (IUGR), and cord blood gas status in the three groups. The prevalence
      of non-reassuring FHR and cord blood gas status of these three groups was also
      compared with their prevalence in 65 women with low-risk pregnancies. Multiple
      logistic regression analysis was performed to determine the association between
      rLD and maternal-fetal parameters. RESULTS: Levels of systolic and diastolic
      blood pressure were similar among the three groups. Severe UP was diagnosed
      significantly earlier, was associated with significantly lower gestational age,
      and infants with lighter birth weight (P < 0.05) compared with GH and mild UP.
      The prevalence of IUGR in severe UP was higher than in GH (54%v. 21%, P < 0.05);
      however, no differences were found in the prevalence of IUGR between mild and
      severe UP (43%v. 54%, P = 0.33). The prevalence of non-reassuring FHR in GH was
      not statistically significant in the low-risk pregnancies (5%v. 9%, P = 0.58). In
      mild and severe UP, the non-reassuring FHRs were more predominant (30% and 43%,
      respectively) than in low-risk pregnancies and GH (P < 0.05). The rLD was more
      common in the group with severe UP and accounted for 40% of all FHR patterns.
      There was no difference in the incidence of low pH among the groups. However,
      fetuses in pregnancies involving severe UP were significantly hypoxemic when
      compared with others. Multiple logistic regression analysis showed that worsening
      proteinuria (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.4-12.9) and
      IUGR (OR, 3.8; 95% CI, 1.2-11.5) increased the risk of rLD. Rates of preterm
      birth at less than 32 weeks (OR, 0.7; 95% CI, 0.2-2.5) and severe hypertension
      (OR, 0.5; 95% CI, 0.2-1.3) were not significant. CONCLUSION: In pre-eclampsia,
      the presence of severe proteinuria is associated with an increased likelihood of
      rLD.

PMID- 16445529
TI  - Accurate preoperative diagnosis and laparoscopic removal of the cavitated non
      communicated uterine horn for obstructive Mullerian anomalies.
AB  - Obstructive Mullerian anomalies cause severe dysmenorrhea following menarche as a
      result of disturbed menstrual outflow. Therefore, surgical management such as
      extirpation of the obstructive uterine horn is required for treatment of these
      patients. It is necessary to have a detailed understanding of the pathological
      conditions of the pelvic organs and urinary system prior to surgery. We report
      three cases of reproductive, nulligravid patients diagnosed as having obstructive
      Mullerian anomalies. Preoperative accurate diagnosis was obtained by magnetic
      resonance imaging (MRI) and 3-D computed tomography (CT) angiography.
      Laparoscopic resection of the rudimentary uterine horn was performed safely and
      completely, and resolved all problems. MRI and 3-D CT angiography are useful
      tools for diagnosing complex Mullerian anomalies, and operative laparoscopy may
      be an alternative treatment for these cases.

PMID- 16445530
TI  - Increase in serum concentrations of inhibin in early onset pre-eclampsia with
      intrauterine growth restriction.
AB  - AIM: Recently, it has been hypothesized that reduced placental blood flow in
      early pregnancy causes changes in endothelial function, leading to pre-eclampsia.
      To clarify this clinically, we assessed serum concentrations of inhibin and uric
      acid in pre-eclamptic women compared with those of normotensive pregnant women.
      METHODS: One hundred and forty normotensive pregnant women (at 20-41 weeks'
      gestation) and 50 women with pre-eclampsia (at 24-41 weeks' gestation) were the
      study subjects. Pre-eclamptic women were classified according to the new criteria
      for pregnancy-induced hypertension produced by the Japanese Society of Obstetrics
      and Gynecology (JSOG). Serum concentrations of uric acid and inhibin were
      measured enzymatically and by radioimmunoassay, respectively. RESULTS: Serum
      concentrations of inhibin and uric acid in the pre-eclamptic women were
      significantly higher than in gestational age-matched normotensive pregnant women.
      There were significant correlations among inhibin and uric acid, blood pressure
      and birth weight. According to JSOG criteria, of the 50 pre-eclamptic women, 18
      were early onset (EO), including 16 cases complicated by intrauterine growth
      restriction (IUGR), and 32 cases were late onset, including 12 cases complicated
      by IUGR. In the patients with EO and IUGR, serum concentrations of inhibin, but
      not uric acid, were significantly elevated as compared with those of the other
      pre-eclamptic women. CONCLUSION: The results suggest that an increase in the
      serum concentration of inhibin seen in EO pre-eclampsia, together with IUGR,
      might be a cause of reduced placental blood flow.

PMID- 16445531
TI  - Bilateral pleural endometriosis.
AB  - The patient was a 40-year-old woman with a 1-year history of catamenial chest
      pain and a recent bilateral hemothorax. She underwent a left thoracotomy for
      surgical pleurodesis, and a pleural biopsy. Subsequently, she had a hysterectomy
      in conjunction with an oophorectomy. The pathologic investigation of the pleura
      revealed an endometrial implant. The postoperative course was uneventful with no
      recurrence of hemothorax and chest pain during the first 6 months and at the
      patient's follow-up. This is a very rare case of a patient with thoracic
      endometriosis presenting with bilateral hemothorax.

PMID- 16445532
TI  - Prenatal diagnosis of bilateral diaphragmatic hernia by fetal sonography.
AB  - This report describes a case of prenatally diagnosed bilateral diaphragmatic
      hernia. At 22 weeks' gestation, ultrasound revealed a cystic structure behind the
      fetus's heart on the axial image at the level of the cardiac four-chamber view.
      This suggested a left-sided congenital diaphragmatic hernia with herniation of
      the stomach into the left hemithorax. However, the left-to-right midline shift of
      the heart was minimal, which is not typical of left-sided congenital
      diaphragmatic hernia. Throughout the 30th week of gestation, the right and left
      branches of the pulmonary artery were hypoplastic compared with the values in
      normal fetuses of the same gestational age. The presumptive diagnosis was
      bilateral congenital diaphragmatic hernia. A female newborn weighing 2900 g was
      delivered at 37 weeks' gestation, and she died at 7 h of age. An autopsy revealed
      large defects on both sides of the diaphragm. In conclusion, prenatal diagnosis
      of bilateral diaphragmatic hernia is possible with fetal sonography.

PMID- 16445533
TI  - Parathyroid hormone-related protein as a potential tumor marker: a case report of
      ovarian clear cell carcinoma.
AB  - Hypercalcemia is one of the important paraneoplastic syndromes, mostly occurring
      in patients with advanced cancer. Clear cell carcinoma is known to be one of the
      most common histological subtypes of ovarian tumor associated with hypercalcemia.
      We present a case of ovarian clear cell carcinoma with hypercalcemia caused by
      elevated serum parathyroid hormone-related protein (PTHrP). PTHrP mRNA and
      protein were detected by reverse transcription-polymerase chain reaction and
      immunohistochemical analysis in the primary and metastasis lesions. Serum calcium
      and PTHrP levels returned to normal after antihypercalcemic treatment and a
      radical operation, but they elevated along with the recurrence. Because tumor
      markers such as carcinoembryonic antigen, carbohydrate antigen (CA)125 and CA19-9
      were unstable owing to the patient's liver cirrhosis and were not reliable data
      for management, serum calcium and PTHrP levels are shown to have been a potential
      indicator of the recurrence in this case.

PMID- 16445534
TI  - Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in
      patients with advanced epithelial ovarian cancer who are inadequate for optimum
      primary surgery.
AB  - AIM: This study was performed to evaluate the efficacy of neoadjuvant
      chemotherapy (NAC) with paclitaxel and cisplatin in patients with advanced
      epithelial ovarian cancer who were inadequate for primary optimal surgery.
      METHODS: Patients with histologically confirmed epithelial ovarian cancer at
      International Federation of Gynecology and Obstetrics stages IIIc/IV that was
      unresectable according to computed tomography findings were eligible for this
      study. Three cycles of paclitaxel plus cisplatin NAC were administered and the
      response was evaluated. Patients were then selected for interval debulking
      surgery or three cycles of additional chemotherapy with the same regimen
      according to the resectability and response. Interval debulking surgery followed
      by second-line chemotherapy was applied to patients with no response to NAC.
      During the same period, patients who did not agree to the protocol were treated
      by the conventional method of tumor debulking surgery followed by adjuvant
      chemotherapy, and served as the control group. A comparison of both groups of
      patients was carried out. RESULTS: A total of 40 patients were involved in the
      study. All patients were evaluable. Eighteen patients underwent NAC and 22
      patients were treated by conventional therapy. Optimal debulking was possible in
      14 patients (77.8%) in the NAC group and in 10 patients (45.5%) in the
      conventional therapy group (P = 0.04). The mean estimated blood loss was 620 cc
      (range: 300-1500 cc) in the NAC group and 1061 cc (range: 300-3500 cc) in the
      conventional therapy group (P = 0.04). However, no significant differences were
      found in the disease-free and overall survival rates between the two groups (P =
      0.48 and P = 0.61, respectively). CONCLUSION: NAC provided a higher rate of
      optimum cytoreduction and equivalent survival with less invasive surgery and
      reduced morbidity compared with conventional therapy in patients with advanced
      epithelial ovarian cancer inadequate for primary optimum surgery. Therefore, NAC
      may be a valuable alternative treatment for these patients.

PMID- 16445535
TI  - Comparison of maternal-fetal outcomes in gestational diabetes and lesser degrees
      of glucose intolerance.
AB  - AIM: To determine the relationships between maternal and fetal outcomes and
      gestational diabetes mellitus (GDM), impaired fasting glucose (IFG) and impaired
      glucose tolerance (IGT), respectively. METHODS: A retrospective cohort study
      design was used with 149 patients with abnormal oral glucose tolerance test
      (OGTT) and 149 normal patients. Statistical analysis used was the chi-squared
      test, Fisher's exact test or the Student's t-test, as appropriate. P < 0.05 was
      considered significant. RESULTS: The level of hyperglycemia according to the OGTT
      (World Health Organization criteria) was associated with pre-eclampsia,
      polyhydramnios and macrosomia in GDM patients. There was no increase in the
      complications of preterm labor and premature rupture of membranes, despite the
      increased risk of polyhydramnios. Although treated with insulin, macrosomia still
      occurred in patients with GDM, but there was no shoulder dystocia as there was an
      increase in the incidence of cesarean section (CS). The IGT group was not
      associated with adverse fetal or maternal outcomes, but there was an increase in
      intervention and the incidence of CS. The IFG group was associated with a
      significantly increased risk of pre-eclampsia and macrosomia. These findings
      challenge the concept of IFG being a lesser pathology than GDM. Further
      prospective studies with a larger number of patients are needed to ascertain the
      significance of these findings. CONCLUSION: There was an increased risk of pre
      eclampsia and macrosomia in both the GDM and IFG patients, but IGT was not
      associated with adverse fetal or maternal outcomes.

PMID- 16445537
TI  - Comments on perinatal management of cervicoisthmic pregnancy.

PMID- 16445538
TI  - A 'perfect storm' in developing countries: economic growth and the alcohol
      industry.

PMID- 16445539
TI  - Medications to treat heavy drinking: are we there yet?

PMID- 16445540
TI  - Alcohol and the so-called prevention paradox: how does it look today?

PMID- 16445541
TI  - Comments on Skog (2006): the prevention paradox always looked to me like a
      sleight of hand.

PMID- 16445542
TI  - Issues for further reflections: comments on Skog (2006).

PMID- 16445543
TI  - Understanding the prevention paradox: drinkers and drinking. A comment on Skog
      (2006).

PMID- 16445544
TI  - Many important alcohol problems are widely dispersed: comment on Skog (2006).

PMID- 16445545
TI  - The dangerousness of drugs.

PMID- 16445546
TI  - Conversation with M. Douglas Anglin.

PMID- 16445547
TI  - Substance abuse and dependence in prisoners: a systematic review.
AB  - AIMS: To review studies of the prevalence of substance abuse and dependence in
      prisoners on reception into custody. DESIGN AND METHOD: A systematic review of
      studies measuring the prevalence of drug and alcohol abuse and dependence in male
      and female prisoners on reception into prison was conducted. Only studies using
      standardized diagnostic criteria were included. Relevant information, such as
      mean age, gender and type of prisoner, was recorded for eligible studies. The
      prevalence estimates were compared with those from large cross-sectional studies
      of prevalence in prison populations. FINDINGS: Thirteen studies with a total of
      7563 prisoners met the review criteria. There was substantial heterogeneity among
      the studies. The estimates of prevalence for alcohol abuse and dependence in male
      prisoners ranged from 18 to 30% and 10 to 24% in female prisoners. The prevalence
      estimates of drug abuse and dependence varied from 10 to 48% in male prisoners
      and 30 to 60% in female prisoners. CONCLUSIONS: The prevalence of substance abuse
      and dependence, although highly variable, is typically many orders of magnitude
      higher in prisoners than the general population, particularly for women with drug
      problems. This highlights the need for screening for substance abuse and
      dependence at reception into prison, effective treatment while in custody, and
      follow-up on release. Specialist addiction services for prisoners have the
      potential to make a considerable impact.

PMID- 16445548
TI  - A meta-analysis of voucher-based reinforcement therapy for substance use
      disorders.
AB  - AIMS: To systematically investigate the effectiveness of voucher-based
      reinforcement therapy for the treatment of substance use disorders. METHODS:
      Effect sizes and 95% confidence intervals were calculated for studies published
      between January 1991 and March 2004 that utilized voucher-based reinforcement
      therapy (VBRT) or related monetary-based incentives to treat substance use
      disorders (SUDs). FINDINGS: Thirty studies involved interventions targeting
      abstinence from drug use using experimental designs where effects on treatment
      outcome could be attributed to the VBRT intervention. The estimated average
      effect size (r) for those studies was 0.32 (95% CI 0.26-0.38). Analyses of
      variables thought to moderate VBRT effect sizes revealed that more immediate
      voucher delivery and greater monetary value of the voucher were associated with
      larger effect sizes. Additional studies were identified wherein VBRT was used to
      target clinic attendance (n = 6) or medication compliance (n = 4). VBRT studies
      targeting attendance produced average effect sizes of 0.15 (95% CI 0.02-0.28),
      while those that targeted medication compliance produced an average effect of
      0.32 (95% CI 0.15-0.47). No significant moderators were identified for these 10
      studies. CONCLUSIONS: Overall, VBRT generated significantly better outcomes than
      did control treatments. These results further support the efficacy of VBRT,
      quantify the magnitude of its effects, identify significant moderators and
      suggest potential directions for future research.

PMID- 16445549
TI  - Ethyl sulphate: a direct ethanol metabolite reflecting recent alcohol
      consumption.
AB  - BACKGROUND: Ethyl sulphate (EtS), a direct ethanol metabolite, appears to offer
      potential as a biomarker for recent alcohol consumption. Although its window of
      assessment is similar to that of ethyl glucuronide (EtG), there are differences
      between the two markers in their pathways for formation and degradation. AIMS:
      (a) To assess the excretion of EtS compared to EtG and ethanol in drinking
      experiments with healthy volunteers, and (b) to elucidate the possibility of
      using the two metabolites for monitoring abstinence in substance use disorder
      patients during rehabilitation treatment. DESIGN, SETTING, PARTICIPANTS: (a) Nine
      drinking experiments were performed by six healthy volunteers (two females, four
      males), with a mean age of 34.1 years (20-62), average oral intake of 0.2 g/kg
      ethanol (0.1-0.61), and having 74 spot urine samples. (b) Thirty-six substance
      abuse patients (mean age 41.9 years, 20-59; 22 males, 14 females) in a
      rehabilitation programme after withdrawal, producing 98 urine samples. Ethyl
      glucuronide and ethyl sulphate were measured using liquid chromatography tandem
      mass spectrometry (LC-MS/MS) using d5-EtG and d5-EtS, respectively, as an
      internal standard. FINDINGS: (a) VOLUNTEERS: EtG and EtS were detectable for up
      to 36 hours and reached the limits of determination in urine at 20.6 hours and
      21.2 hours (median), respectively, after ethanol intake. EtG-100 (standardized to
      a creatinine of 100 mg/dl) reached its maximum level at 2.8 hours and EtS-100 at
      2.1 hours (median) after the beginning of the experiment. Of the ethanol
      ingested, 0.022% was excreted as EtS in one volunteer. Eight samples were
      positive for EtS only and six for EtG only. Spearman's rank correlation
      coefficients of 0.84 (P < 0.0001) between EtG and EtS and 0.87 (P < 0.0001)
      between EtG-100 and EtS-100 were found. (b) PATIENTS: of the 98 urine samples
      evaluated, 27 were positive for EtS and of these only 20 were also positive for
      EtG. Spearman's rank correlation coefficients of 0.84 (P < 0.0001) between EtG
      and EtS and 0.82 (P < 0.0001) between EtG-100 and EtS-100 were found.
      CONCLUSIONS: The data from patients and volunteers suggest that the direct
      ethanol metabolite ethyl sulphate has the potential to serve as a biomarker of
      recent ethanol intake. Because EtG and EtS are formed via different pathways they
      might be used conjointly, thereby increasing sensitivity.

PMID- 16445551
TI  - Enforcing the minimum drinking age: state, local and agency characteristics
      associated with compliance checks and Cops in Shops programs.
AB  - AIMS: To identify state, local and organizational characteristics associated with
      local law enforcement agencies' implementation of two dramatically different
      approaches to enforcement of underage drinking laws: compliance checks and Cops
      in Shops programs. Compliance checks use underage decoys to attempt to purchase
      alcohol from retail merchants, while Cops in Shops programs deploy undercover law
      enforcement officers in alcohol outlets to detect and cite persons under the age
      of 21 who attempt to purchase alcohol. DESIGN: Cross-sectional telephone
      interview conducted as part of the Tobacco Enforcement Study (TES), which
      examined enforcement of laws related to youth access to tobacco. SETTING: Data
      were collected in 1999 among law enforcement agencies in all 50 states of the
      United States. PARTICIPANTS: Representatives of city police departments,
      departments of public safety, sheriffs or county police were included (n = 920
      local agencies). MEASUREMENTS: Alcohol compliance checks and Cops in Shops
      programs were the primary outcomes. Covariates included state level policies
      (e.g. beer tax), agency resources (e.g. number of sworn officers) and community
      demographics (e.g. college dormitory population). FINDINGS: Local enforcement
      agencies were more likely to perform alcohol compliance checks than to have a
      Cops in Shops program (73.9% compared to 41.1% in cities > 25 000 and 55.7%
      compared to 23.9% in cities < or = 25 000). Conducting compliance checks for
      tobacco age-of-sale laws was positively associated with alcohol compliance checks
      and Cops in Shops (OR 3.30, P < 0.001; OR 1.84, P = 0.001, respectively). Having
      a Drug Abuse Resistance Education (DARE) officer was negatively related to
      conducting compliance checks (OR 0.67, P = 0.03). Special community policing
      units were associated with departments having Cops in Shops programs (OR 1.80, P
      = 0.006). CONCLUSIONS: This study used a nationally representative sample of
      communities to better understand state and local factors that shape local law
      enforcement agencies' use of two distinct approaches to underage drinking
      enforcement. The strong link observed between tobacco and alcohol compliance
      checks may indicate a culture within some law enforcement agencies supporting
      strict enforcement of age-of-sale laws.

PMID- 16445550
TI  - Rates and predictors of relapse after natural and treated remission from alcohol
      use disorders.
AB  - AIMS: This study examined the rates and predictors of 3-year remission, and
      subsequent 16-year relapse, among initially untreated individuals with alcohol
      use disorders who did not obtain help or who participated in treatment and/or
      Alcoholics Anonymous in the first year after recognizing their need for help.
      DESIGN AND MEASURES: A sample of individuals (n = 461) who initiated help-seeking
      was surveyed at baseline and 1 year, 3 years, 8 years and 16 years later.
      Participants provided information on their life history of drinking, alcohol
      related functioning and life context and coping. FINDINGS: Compared to
      individuals who obtained help, those who did not were less likely to achieve 3
      year remission and subsequently were more likely to relapse. Less alcohol
      consumption and fewer drinking problems, more self-efficacy and less reliance on
      avoidance coping at baseline predicted 3-year remission; this was especially true
      of individuals who remitted without help. Among individuals who were remitted at
      3 years, those who consumed more alcohol but were less likely to see their
      drinking as a significant problem, had less self-efficacy, and relied more on
      avoidance coping, were more likely to relapse by 16 years. These findings held
      for individuals who initially obtained help and for those who did not.
      CONCLUSIONS: Natural remission may be followed by a high likelihood of relapse;
      thus, preventive interventions may be indicated to forestall future alcohol
      problems among individuals who cut down temporarily on drinking on their own.

PMID- 16445552
TI  - Trends in alcohol-related harms and offences in a liberalized alcohol
      environment.
AB  - AIM: To assess alcohol-related harms and offences in New Zealand from 1990 to
      2003, a period of alcohol policy liberalization, that included the lowering of
      the purchase age from 20 to 18 years in 1999. DESIGN, SETTING AND PARTICIPANTS:
      Time trend analyses were carried out on routinely collected data for prosecutions
      for driving with excess alcohol; alcohol-involved vehicle crashes (all and fatal)
      and prosecutions for disorder offences. These were carried out separately for
      those aged 14-15, 16-17, 18-19, 20-24 and 25 years and over. MEASUREMENTS: Rates
      of: prosecutions for driving with excess alcohol (1990-2003); rates of alcohol-
      involved vehicle crashes (all and fatal) (1990-2003); and rates of prosecutions
      for disorder offences (1994-2003). FINDINGS: Effects of alcohol policy
      liberalization: positive trends were found in the rates of prosecutions for
      disorder in the 16-17, 18-19, 20-24 and 25 + age groups; with 18-19-year-olds and
      16-17-year-olds having the largest rates and largest positive trend in rates. For
      16-17-year-olds, there was a positive trend in the rates of prosecutions for
      excess breath alcohol. Negative trends in rates were found for alcohol-related
      crashes (all and fatal) among all age groups. Negative trends for those over 16
      17 years were found for prosecutions for driving with excess breath alcohol (this
      was prior to the lowering of the purchase age). Effects of lowering the minimum
      purchase age: the lowering of minimum purchase age coincided with an increase in
      the trend of alcohol-related crashes for 18-19-year-olds; the next largest
      increase was among the 20-24-year-olds (all other age groups also increased but
      at a much lower rate). A similar result was found for driving with excess alcohol
      for those aged 18-19 (and those aged 20-24 years). An increase in the rates of
      prosecutions for disorder offences occurred for the 14-15-year-old group
      following the lowering of the purchase age. CONCLUSION: The liberalization of
      alcohol throughout the 1990s may have influenced younger people more, as
      reflected in increases in their disorder offences and drink driving. The lowering
      of the minimum purchase age may have led to an increase in drink-driving among
      the 18-19-year-olds (those directly affected by the change in purchase age).

PMID- 16445553
TI  - Economic and cultural correlates of cannabis use among mid-adolescents in 31
      countries.
AB  - AIMS: To examine cannabis use among mid-adolescents in 31 countries and
      associations with per-capita personal consumer expenditure (PCE), unemployment,
      peer factors and national rates of cannabis use in 1999. DESIGN, PARTICIPANTS AND
      MEASUREMENT: Nationally representative, self-report, classroom survey with 22 223
      male and 24 900 female 15-year-olds. Country characteristics were derived from
      publicly available economic databases and previously conducted cross-national
      surveys on substance use. FINDINGS: Cannabis use appears to be normative among
      mid-adolescents in North America and several countries in Europe. The life-time
      prevalence of cannabis use was 26% among males and 15% among females and was
      lowest for males and females in the former Yugoslav Republic (TFYR) of Macedonia:
      2.5% and to 2.5%, respectively; and highest for males in Switzerland (49.1%) and
      in Greenland for females (47.0%). The highest prevalence of frequent cannabis use
      (more than 40 times in life-time) was seen in Canada for males (14.2%) and in the
      United States for females (5.5%). Overall, life-time prevalence and frequent use
      are associated with PCE, perceived availability of cannabis (peer culture) and
      the presence of communities of older cannabis users (drug climate). CONCLUSIONS:
      As PCE increases, cannabis use may be expected to increase and gender differences
      decrease. Cross-national comparable policy measures should be developed and
      evaluated to examine which harm reduction strategies are most effective.

PMID- 16445554
TI  - Prevalence of HIV, hepatitis C and syphilis among injecting drug users in Russia:
      a multi-city study.
AB  - OBJECTIVES: To estimate the prevalence of HIV, hepatitis C virus (HCV) and
      syphilis in injecting drug users (IDUs) in Russia. METHODS: Unlinked anonymous
      cross-sectional survey of 1473 IDUs recruited from non-treatment settings in
      Moscow, Volgograd and Barnaul (Siberia), with oral fluid sample collection for
      HIV, HCV antibody (anti-HIV, anti-HCV) and syphilis testing. RESULTS: Prevalence
      of antibody to HIV was 14% in Moscow, 3% in Volgograd and 9% in Barnaul. HCV
      prevalence was 67% in Moscow, 70% in Volgograd and 54% in Barnaul. Prevalence of
      positive syphilis serology was 8% in Moscow, 20% in Volgograd and 6% in Barnaul.
      Half of those HIV positive and a third of those HCV positive were unaware of
      their positive status. Common risk factors associated with HIV and HCV infection
      across the cities included both direct and indirect sharing of injecting
      equipment and injection of home-produced drugs. Among environmental risk factors,
      we found increased odds of anti-HIV associated with being in prison in Moscow,
      and some association between official registration as a drug user and anti-HIV
      and anti-HCV. No associations were found between sexual risk behaviours and anti
      HIV in any city. CONCLUSIONS: HIV prevalence among IDUs was markedly higher than
      city routine surveillance data suggests and at potentially critical levels in
      terms of HIV prevention in two cities. HCV prevalence was high in all cities.
      Syphilis prevalence highlights the potential for sexual risk and sexual HIV
      transmission. Despite large-scale testing programmes, knowledge of positive
      status was poor. The scaling-up of harm reduction for IDUs in Russia, including
      sexual risk reduction, is an urgent priority.

PMID- 16445556
TI  - Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy
      comparison study.
AB  - AIMS: To evaluate the efficacy and safety of methadone versus buprenorphine
      treatment in pregnant opioid-dependent women. DESIGN: Randomized, double-dummy,
      double-blind, flexible-dosing comparison study. SETTING: Addiction Clinic at the
      Medical University of Vienna, Austria. PARTICIPANTS: Eighteen women were assigned
      randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during
      weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six
      in the methadone and eight in the buprenorphine group). INTERVENTION: Sublingual
      buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day),
      with matched placebos. MEASUREMENTS: Mothers: retention in treatment, urine
      toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence
      syndrome (NAS) in severity and duration. FINDINGS: There was somewhat greater
      retention in the buprenorphine group but significantly lowered use of additional
      opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of
      NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine
      groups (mean 72 hours after last medication); 43% did not require NAS-treatment
      with short treatment duration in both groups (mean 5 days). CONCLUSION: This
      preliminary study had limited power to detect differences but the trends observed
      suggest this kind of research is practicable and that further studies are
      warranted.

PMID- 16445555
TI  - A comparison of contingency management and cognitive-behavioral approaches for
      stimulant-dependent individuals.
AB  - AIMS: Previous research has reported that both contingency management (CM) and
      cognitive-behavioral therapy (CBT) are efficacious interventions for the
      treatment of stimulant abusers. The present study sought to directly compare the
      effectiveness of (CM) and (CBT) alone and in combination in reducing stimulant
      use. DESIGN: Randomized clinical trial. PARTICIPANTS: Stimulant-dependent
      individuals (n = 171). INTERVENTION: CM, CBT or combined CM and CBT, 16-week
      treatment conditions. CM condition participants received vouchers for stimulant
      free urine samples. CBT condition participants attended three 90-minute group
      sessions each week. MEASUREMENTS: Participants were interviewed at baseline and
      weeks 17, 26 and 52. Measures included psychiatric disorders and alcohol and drug
      use and concomitant social problems. FINDINGS: CM procedures produced better
      retention and lower rates of stimulant use during the study period. Self-reported
      stimulant use was reduced from baseline levels at all follow-up points for all
      groups and urinalysis data did not differ between groups at follow-up. While CM
      produced robust evidence of efficacy during treatment application, CBT produced
      comparable longer-term outcomes. There was no evidence of an additive effect when
      the two treatments were combined. CONCLUSIONS: This study suggests that CM is an
      efficacious treatment for reducing stimulant use and is superior during treatment
      to a CBT approach. CM is useful in engaging substance abusers, retaining them in
      treatment and helping them achieve abstinence from stimulant use. CBT also
      reduces drug use from baseline levels and produces comparable outcomes on all
      measures at follow-up.

PMID- 16445557
TI  - Prediction of adolescent smoking from family and social risk factors at 5 years,
      and maternal smoking in pregnancy and at 5 and 14 years.
AB  - AIMS: This study examines associations between maternal smoking and family,
      social or child risk factors when the child is aged 5 and adolescent smoking. The
      influence of mothers who smoke in pregnancy or continue to smoke at 14 years was
      also examined. DESIGN: The Mater-University of Queensland Study of Pregnancy is a
      prospective cohort study. PARTICIPANTS: Participants included 8556 women enrolled
      between 1981 and 1984 at their first antenatal visit. Completed questionnaires
      were obtained for 7223 offspring, comprising the study birth cohort. Of the 7223
      eligible children a total of 4541 had information on both maternal smoking when
      the child was aged 5 years and adolescent smoking at 14 years. MEASUREMENTS:
      Measures included maternal smoking during pregnancy and when the child was aged 5
      and 14 years, child smoking at 14 years, maternal alcohol use, child behaviour
      problems and social and demographic variables. FINDINGS: Adolescent smoking was
      predicted by a risk score at 5 years involving maternal smoking and alcohol use,
      non-married status, having a partner who had ever been arrested, having four or
      more children in the household, and child aggression at 5 years. Continued
      maternal smoking from 5 to 14 years was associated strongly with adolescent
      smoking. There was also evidence that smoking in late pregnancy may exert an
      independent effect on adolescent smoking. CONCLUSIONS: The results suggest the
      possibility of a direct effect of prenatal smoking on adolescent smoking and
      highlight a set of environmental risk factors in the development of adolescent
      smoking. These risk factors may be used as early warning signs that intervention
      may be needed, and given the similarities with risk factors for other adverse
      childhood outcomes, the benefits of early intervention may extend beyond smoking
      to other problem behaviours. The possibility of being able to predict other
      disorders, because of these associations, also warrants further investigation.

PMID- 16445559
TI  - Early-onset alcoholism: a separate or unique predictor of delay discounting?
      Comment on Dom et al. (2006).

PMID- 16445558
TI  - What came first? Comment on Dom et al. (2006).

PMID- 16445561
TI  - Comments on Rossow & Romelsjo (2006). Dispelling illusions about the prevention
      paradox.

PMID- 16445562
TI  - Comments on Rossow & Romelsjo (2006). The prevention paradox.

PMID- 16445565
TI  - Gene-environment interactions, neuronal dysfunction and pathological plasticity
      in Huntington's disease.
AB  - Huntington's disease (HD) is a fatal autosomal dominant disorder in which there
      is progressive neurodegeneration producing motor, cognitive and psychiatric
      symptoms. The dynamic mutation that causes the disease is common to numerous
      other brain disorders, which may share similar pathogenic mechanisms. Much
      progress has been made in the past decade in understanding how a trinucleotide
      (CAG) repeat expansion, encoding an expanded polyglutamine tract in the
      huntingtin protein, induces dysfunction at molecular and cellular levels. The
      present review integrates various lines of experimental evidence in an attempt to
      move towards a unifying mechanistic framework, which may explain the pathogenesis
      of HD, from molecular through to neuronal network and behavioural levels. Recent
      evidence, using transgenic mouse models, also suggests that environmental factors
      can modify the onset and progression of HD. The effects of specific environmental
      manipulations are discussed in the context of gene-environment interactions and
      experience-dependent plasticity in the healthy and diseased brain, particularly
      the cerebral cortex.

PMID- 16445566
TI  - Effects of intravenous ABT-870 (iron (III)-hydroxide oligosaccharide) on mean
      arterial pressure and heart rate in the anaesthetized beagle: comparison with
      other iron-containing haematinic agents.
AB  - Iron-deficiency anaemia, a complication of end-stage renal disease (ESRD), is
      often treated with parenteral iron therapies that have been shown to produce dose
      limiting hypotension in patients. ABT-870 (iron-(III)-hydroxide-oligosaccharide)
      is comprised of elemental iron complexed with oligosaccharide, a composition that
      we hypothesised would allow the hypotensive effects of parenteral iron therapy to
      be overcome, thus allowing a rapid rate of infusion to be well tolerated. Mean
      arterial pressure (MAP) and heart rate (HR) were monitored in anaesthetized dogs
      following the infusion of ABT-870 and iron sucrose administered at doses of 7.1
      and 21.3 mg/kg using a rapid 30 s infusion. ABT-870 and iron sucrose were also
      monitored at doses of 7.1, 21.3 and 50 mg/kg administered over a 10 min period.
      Sodium ferric gluconate complex (SFGC) was administered in an identical fashion
      at doses of 12.5 and 31.2 mg/kg. A 30 s rapid infusion of ABT-870 at doses of 7.1
      and 14.3 mg/kg or a 10 min infusion of ABT-870 at doses of 7.1 and 21.3 mg/kg
      produced little effect on MAP and HR. Infusion of the highest dose of ABT-870 (50
      mg/kg) produced no consistent hypotension, but did produce an increase in HR
      (maximal increase 35 +/- 9 b.p.m.), an effect that lasted only 15 min. A 30 s
      rapid infusion of iron sucrose at 7.1 mg/kg produced modest increases in MAP and
      HR (5 +/- 1 mmHg and 5 +/- 2 b.p.m., respectively). However, rapid infusion of
      iron sucrose at 14.3 mg/kg produced hypotension (to -8 +/- 1 mmHg below baseline)
      and exerted variable, biphasic effects on HR ranging from -16 to +50 b.p.m.
      Although 10 min infusion of iron sucrose at 7.1 mg/kg exerted little effect on
      MAP and HR, at doses of 21.3 and 50 mg/kg iron sucrose elicited a profound dose
      dependent decrease in MAP (-34 +/- 11 and -83 +/- 5 mmHg, respectively) and a
      pronounced increase in HR ranging from 32 to 49 b.p.m. above baseline. A 10 min
      infusion of SFGC at doses of 12.5 and 31.2 mg/kg produced a dose-dependent
      decrease in MAP (-28 +/- 18 and -67 +/- 12 mmHg below baseline) and a marked
      increase in HR (26 +/- 11 and 94 +/- 15 b.p.m. above baseline). In conclusion,
      unlike iron sucrose and SFGC, high doses of ABT-870 failed to exert consistent
      hypotensive effects. These data demonstrate that ABT-870 may have a substantial
      therapeutic window and considerable clinical potential for iron-replacement
      therapy.

PMID- 16445567
TI  - Cysteinyl leukotrienes and leukotriene B mediate vasoconstriction to arginine
      vasopressin in rat basilar artery.
AB  - Arginine vasopressin (AVP) has been reported to be involved in the development of
      cerebral vasospasm after haemorrhage and cerebral oedema following ischaemia.
      Endogenously produced 5-lipoxygenase metabolites are able to contract isolated
      endothelium-preserved arterial strips and modulate vascular permeability. The
      present study addresses the role of 5-lipoxygenase and its products, namely
      cysteinyl leukotrienes (CysLTs) and leukotriene (LT) B4, in the contraction
      induced by AVP in rat basilar artery. Contractile responses to LTD4, LTC4, LTB4
      or AVP were assessed in spiral preparations of rat endothelium-intact basilar
      artery. Contractions to AVP were determined in the absence or presence of 5
      lipoxygenase inhibitors or CysLT1 or BLT receptor antagonists. Contractile
      responses to leukotrienes and AVP are expressed as a percentage of the
      contraction induced by 80 mmol/L KCl. Leukotriene D4, LTC4 and LTB4 acted as
      vasoconstrictor agents in rat basilar artery, causing contractions (all at
      concentrations of 1 micromol/L) of 42 +/- 13, 54 +/- 15 and 25 +/- 6% of the
      response to 80 mmol/L KCl, respectively. A concentration-response curve was
      constructed for AVP over the range 1 pmol/L to 10 nmol/L and an EC50 value of
      0.19 +/- 0.02 nmol/L (n = 30) was determined. The presence of the 5-lipoxygenase
      inhibitors ZM 230487 (10 nmol/L and 0.1 and 1 micromol/L) and AA 861 (1, 3, 10,
      and 30 micromol/L), the CysLT1 receptor antagonist MK 571 (3, 10 and 30
      micromol/L) or the BLT receptor antagonists CP 105696 and LY 255283 (3, 10 and 30
      micromol/L for both) in the organ bath significantly attenuated the contractions
      induced by AVP in rat basilar artery (P < 0.05). The experimental results of the
      present study provide the first evidence for the involvement of CysLTs and LTB4
      in the in vitro constriction induced by AVP in rat basilar artery. In the context
      of previously reported involvement of AVP in the development of cerebral
      vasospasm and oedema, the present study draws attention to the potential role
      played by the 5-lipoxygenase pathway in these pathological processes.

PMID- 16445568
TI  - Acute digoxin loading reduces ABCA8A mRNA expression in the mouse liver.
AB  - Human ABCA8, a new member of the ATP binding cassette (ABC) transporter family,
      transports certain lipophilic drugs, such as digoxin. To investigate the roles of
      this transporter, we cloned a mouse homologue of ABCA8, from a mouse heart cDNA
      library, named ABCA8a. The deduced mouse ABCA8a protein is 66% identical with
      that of human ABCA8 and possesses features common to the ABC superfamily. It was
      found that ABCA8a was mainly expressed in the liver and heart, similar to human
      ABCA8. We further evaluated the effect of acute digoxin (a substrate for ABCA8)
      intoxication on the mRNA expression of ABCA8 using northern blotting with a 3'
      non-coding region as a probe to avoid cross-hybridization with other ABCA genes.
      Following acute digoxin infusion, the mRNA expression of ABCA8 was significantly
      reduced in the liver 12-24 h after injection (14.7% of vehicle treatment), but
      not in the heart and kidney. Real-time quantitative polymerase chain reaction
      analysis confirmed the reduction in ABCA8a mRNA. Similar reductions in ABCA5,
      ABCA7, ABCA8b and ABCA9 mRNA were also observed. A comparable amount of digitoxin
      did not affect ABCA8a mRNA expression in the liver. The results suggest that
      ABCA8 may play a role in digoxin metabolism in the liver.

PMID- 16445569
TI  - Inhibition of mitogen-activated protein kinase kinase enhances apoptosis induced
      by arsenic trioxide in human breast cancer MCF-7 cells.
AB  - Arsenic trioxide (As2O3) has recently been used to treat acute promyelocytic
      leukaemia and has activity in vitro against several solid tumour cell lines where
      the induction of differentiation and apoptosis are the prime effects. The
      mechanism of As2O3-induced cell death has yet to be clarified, especially in
      solid cancers. In the present study, the human breast cancer cell line MCF-7 was
      examined as a cellular model for As2O3 treatment. The involvement of
      extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase
      (JNK) was investigated in As2O3-induced cell death. 3. It was found that As2O3
      activates the prosurvival mitogen-activated protein kinase kinase (MEK)/ERK
      pathway in MCF-7 cells, which, conversely, may compromise the efficacy of As2O3.
      Hence, a combination treatment of As2O3 and MEK inhibitors was investigated to
      determine whether this treatment could lead to enhanced growth inhibition and
      apoptosis in MCF-7 cells. 4. Inhibition of MEK/ERK with the pharmacological
      inhibitors U0126 (10 micromol/L) or PD98059 (20 micromol/L) together with As2O3
      (2 and 5 micromol/L) resulted in a significant enhancement of growth inhibition
      in breast cancer MCF-7 cells as determined by the 3-(4,5-dimethyl-2 thiazoyl)-2,5
      diphenyl-2H-tetrazolium bromide assay and [Methyl-3H]-thymidine incorporation.
      Furthermore, the results demonstrated that combined treatment with As2O3 and the
      MEK1/2 inhibitor U0126 could augment breast cancer MCF-7 cell apoptosis
      approximately twofold compared with the effects of the two drugs alone, as
      determined by Hoechst 33258 or annexin V/propidium iodide (PI) staining and flow
      cytometry. 5. In addition, As2O3 activated p38 in a dose-dependent manner, but
      had no effect on JNK1/2. Treatment with a p38 inhibitor did not prevent As2O3
      induced apoptosis. 6. In conclusion, the results of the present study showed that
      enhanced apoptosis is detected in breast cancer MCF-7 cells in the presence of
      As2O3 and an MEK inhibitor, which may be a new promising adjuvant to current
      breast cancer treatments.

PMID- 16445570
TI  - Effects of trans-resveratrol on hypertension-induced cardiac hypertrophy using
      the partially nephrectomized rat model.
AB  - trans-Resveratrol (resveratrol) has been shown to have beneficial effects on the
      cardiovascular system in a number of studies. It is, however, unclear whether
      this naturally occurring compound can protect against cardiac hypertrophy. The
      aim of the present study was to investigate the effects of resveratrol on cardiac
      hypertrophy in vivo and the potential underlying mechanisms involving endothelin
      (ET), angiotensin (Ang) II and nitric oxide (NO) in partially nephrectomized
      rats. Animal models bearing cardiac hypertrophy were replicated in male Sprague
      Dawley rats following partial nephrectomy (PNX). Resveratrol (10 or 50 mg/kg) was
      administered to rats by gavage for 4 weeks. Simultaneous PNX and sham operation
      controls were simultaneously established in the present study. The systolic blood
      pressure (SBP) of rats was measured at baseline and, along with heart weight,
      after 4 weeks treatment. Serum ET-1, AngII and NO concentrations were determined.
      In the present study, it was shown that, compared with rats in the sham-operated
      group, rats in the PNX group had significantly higher SBP (154.1 +/- 22.7 mmHg),
      heart weight (1.69 +/- 0.24 g) and serum ET-1 (125.70 +/- 26.27 pg/mL) and AngII
      serum concentrations (743.63 +/- 86.50 pg/mL), whereas serum NO concentrations
      were lower (21.1 +/- 6.9 micromol/L; all P < 0.05). These values in the sham
      control group were 114 +/- 10 mmHg, 1.28 +/- 0.13 g, 52.44 +/- 21.85 pg/mL, 528.7
      +/- 158.5 pg/mL and 53.21 +/- 23.87 micromol/L, respectively. After 4 weeks
      treatment with 50 mg/kg resveratrol, SBP, heart weight and ET-1 and AngII
      concentrations had decreased to 135.4 +/- 15.8 mmHg, 1.39 +/- 0.15 g, 97.11 +/-
      26.74 pg/mL and 629.64 +/- 116.18 pg/mL, respectively. However, the serum NO
      concentration had increased to 40.1 +/- 14.6 micromol/L. These values were
      significantly different from those obtained for the PNX group. In conclusion,
      trans-resveratrol appears to be able to protect against the increase in SBP and
      subsequent cardiac hypertrophy in vivo and the mechanisms responsible may
      involve, at least in part, modulation of NO, AngII and ET-1 production.

PMID- 16445571
TI  - Enhanced sympathetic control of renal function in rats congenic for the
      hypertension-related region on chromosome 1.
AB  - Recent studies suggest that a quantitative trait locus (QTL) for blood pressure
      (BP) on rat chromosome 1 is associated with exaggerated sympathetic nervous
      activity. The aim of the present study was to examine whether this QTL can affect
      BP by altering sympathetic control of renal function. Male stroke-prone
      spontaneously hypertensive rats of Izumo origin (SHRSP/Izm), Wistar-Kyoto rats
      (WKY/Izm) and rats from a WKY/Izm congenic strain that contains an SHRSP/Izm
      chromosomal segment between D1Wox29 and D1Arb21 (WKYpch1.0) were used. Clearance
      and micropuncture experiments were performed in anaesthetized rats after acute
      unilateral renal denervation (DN). Mean BP in sham-operated WKYpch1.0 was
      significantly higher than that in WKY/Izm. The DN procedure elicited a greater
      reduction in renal noradrenaline levels in SHRSP/Izm and WKYpch1.0 than in
      WKY/Izm. In both SHRSP/Izm and WKYpch1.0, DN decreased renal vascular resistance
      and filtration fraction, whereas it increased renal blood flow and urinary and
      fractional excretion of sodium. Unilateral renal denervation did not affect these
      parameters in WKY/Izm. Unilateral renal denervation decreased the
      tubuloglomerular feedback (TGF) responsiveness only in SHRSP/Izm, whereas it
      increased the non-perfused early proximal flow rate in SHRSP/Izm and WKYpch1.0.
      The results of the present study indicate that the renal sympathetic nervous
      system exerts enhanced tonic control of the renal vasculature and tubular
      function in SHRSP/Izm and WKYpch1.0, but not in WKY/Izm. Neural impact on the TGF
      response in WKYpch1.0 is indiscernible. Thus, a gene or genes in the QTL may
      influence BP, at least in part, through renal vasoconstriction and sodium
      retention mediated by the enhanced activity of the renal sympathetic nerves.

PMID- 16445572
TI  - Cardiac mitochondrial alterations induced by insulin deficiency and
      hyperinsulinaemia in rats: targeting membrane homeostasis with trimetazidine.
AB  - The present study investigated the ability of trimetazidine (TMZ) to maintain
      cardiac mitochondrial function during the development of insulin deficiency and
      hyperinsulinaemia. The anti-ischaemic drug TMZ is known to increase phospholipid
      synthesis in cardiac membranes and to have a cardioprotective effect. Insulin
      deficiency was obtained by streptozotocin injection and hyperinsulinaemia was
      achieved via a fructose diet. Trimetazidine was incorporated into the diet (7.8
      mg/day) and mitochondrial function was evaluated in skinned cardiac fibres.
      Insulin deficiency decreased mitochondrial affinity for ADP and the index of
      creatine kinase functional activity. This last alteration was partially prevented
      by TMZ treatment. Insulin deficiency strongly decreased n-3 polyunsaturated fatty
      acids, especially the docosahexaenoic acid (DHA) content, in cardiac and
      mitochondrial membranes, inducing a strong increase in the n-6/n-3 ratio.
      Trimetazidine treatment limited the increase in the n-6/n-3 ratio and prevented
      the decrease in DHA content in mitochondrial membranes. Insulin deficiency
      decreased glutamate- and palmitoylcarnitine-supported respiration.
      Hyperinsulinaemia affected neither mitochondrial affinity for ADP nor the index
      of creatine kinase functional activity. Hyperinsulinaemia slightly and
      significantly affected mitochondrial fatty acid composition, by a small increase
      the n-6/n-3 ratio. Trimetazidine did not modify membrane-bound mitochondrial
      function but increased the n-6/n-3 ratio. Moreover, hyperinsulinaemia decreased
      glutamate-supported respiration. In conclusion, modification of membrane
      homeostasis with TMZ partially prevented the alterations in fatty acid
      composition and function in cardiac mitochondria induced by insulin deficiency.
      Three months of hyperinsulinaemia did not modify membrane-bound mitochondrial
      function and had only slight effects on fatty acid composition.

PMID- 16445573
TI  - Feitai, a Chinese herbal medicine, reduces transforming growth factor-beta1 and
      monocyte chemoattractant protein-1 expression in bleomycin-induced lung fibrosis
      in mice.
AB  - Feitai, a Chinese medicine formulation, has been shown to protect against lung
      fibrosis induced by bleomycin (BLM). In the present study, we investigated the
      effect of Feitai on transforming growth factor (TGF)-beta1 and monocyte
      chemoattractant protein-1 (MCP-1), which play important roles in the pathogenesis
      of BLM-induced lung fibrosis. The results demonstrated that Feitai could
      significantly attenuate BLM-induced acute lung inflammation and subsequent lung
      fibrosis. Meanwhile, the expression of MCP-1 and TGF-beta1 mRNA in the lungs
      increased in the BLM-treated group compared with the saline-instilled control
      group and Feitai treatment significantly decreased cytokine expression in BLM
      treated mice. In addition, Feitai diminished the accumulation of MCP-1- and TGF
      beta1-positive cells in lung tissues at the time of peak mRNA levels. In summary,
      the results of the present study indicate that treatment with Feitai ameliorates
      BLM-induced lung fibrosis, at least in part via the inhibition of MCP-1 and TGF
      beta1 expression.

PMID- 16445574
TI  - BAY 41-2272, a potent activator of soluble guanylyl cyclase, stimulates calcium
      elevation and calcium-activated potassium current in pituitary GH cells.
AB  - The effects of BAY 41-2272, a nitric oxide-independent activator of soluble
      guanylyl cyclase, on Ca2+ signalling and ion currents were investigated in
      pituitary GH3 cells. Intracellular Ca2+ concentrations ([Ca2+]i) in these cells
      were increased by BAY 41-2272. Removing extracellular Ca2+ abolished the BAY 41
      2272-induced increase in [Ca2+]i. After [Ca2+]i was elevated by BAY 41-2272 (300
      nmol/L), subsequent application of 1-benzyl-3-(5'-hydroxymethyl-2'-furyl)
      indazole (YC-1; 1 micromol/L) did not increase [Ca2+]i further. In whole-cell
      recordings, BAY 41-2272 reversibly stimulated Ca2+-activated K+ current
      (I(K(Ca))) with an EC50 of 225 +/- 8 nmol/L. At 3 micromol/L, BAY 41-2272
      slightly and significantly decreased L-type Ca2+ current. In the cell-attached
      configuration, BAY 41-2272 (300 nmol/L) enhanced the activity of large
      conductance Ca2+-activated K+ (BK(Ca)) channels. After BK(Ca) channel activity
      was stimulated by spermine NONOate (30 micromol/L) or YC-1 (10 micromol/L) in
      cell-attached patches, subsequent application of BAY 41-2272 (300 nmol/L) further
      increased the channel open probability. In the inside-out configuration, BAY 41
      2272 applied to the intracellular surface of excised patches enhanced BK(Ca)
      channel activity. Unlike 1 micromol/L paxilline, 1H-[1,2,4]oxadiazolol-[4,3a]
      quinoxalin-1-one (ODQ; 10 micromol/L) or heme (10 micromol/L) had no effect on
      BAY 41-2272-stimulated channel activity. BAY 41-2272 caused no shift in the
      activation curve of BK(Ca) channels; however, it did increase the Ca2+
      sensitivity of these channels. At 300 nmol/L, BAY 41-2272 reduced the firing rate
      of spontaneous action potentials stimulated by thyrotropin-releasing hormone (10
      micromol/L). The BK(Ca) channel activity was also enhanced by 300 nmol/L BAY 41
      2272 in neuroblastoma IMR-32 cells. Therefore, the BAY 41-2272-induced increase
      in [Ca2+]i is primarily explained by an increase in Ca2+ influx. The BAY 41-2272
      mediated simulation of IK(Ca) may result from direct activation of BKCa channels
      and indirectly as a result of elevated [Ca2+]i.

PMID- 16445576
TI  - Inhibitory effects of glucosamine on lipopolysaccharide-induced activation in
      microglial cells.
AB  - The aim of the present study was to investigate the effects of glucosamine on
      lipopolysaccharide (LPS)-induced cellular activation in microglia and to evaluate
      the inhibitory mechanisms involved. Lipopolysaccharide (100 ng/mL) was used for
      the activation of primary cultured rat microglial or BV2 microglial cells.
      Changes in intracellular Ca2+ levels and outward K+ currents were measured using
      fura-2/AM and whole-cell patch-clamp methods, respectively. Lipopolysaccharide
      induced expression of tumour necrosis factor (TNF)-alpha mRNA was analysed by
      reverse transcription-polymerase chain reaction. Lipopolysaccharide transformed
      cell morphology into an amoeboid shape in vitro and induced microglial activation
      in vivo, as measured by immunohistochemical staining, but glucosamine inhibited
      this activation. Glucosamine also inhibited LPS-induced Ca2+ influx, outward K+
      currents and TNF-alpha mRNA expression, which are typically representative of
      microglial activation. 4. The results suggest that the inhibitory mechanisms of
      glucosamine on LPS-induced microglial activation include inhibition of Ca2+
      influx and outward K+ currents, as well as downregulation of the microglial
      activator gene TNF-alpha.

PMID- 16445575
TI  - The neuroprotective agent sipatrigine blocks multiple cardiac ion channels and
      causes triangulation of the ventricular action potential.
AB  - Sipatrigine (BW 619C89), a blocker of neuronal Na+ and Ca2+ channels that is
      structurally related to lamotrigine, has been shown to be neuroprotective in
      models of cortical ischaemia. Although associated with cardiovascular effects in
      animal models in vivo, there is no published information concerning the effects
      of sipatrigine on cardiac ion currents and action potentials (AP). The aim of the
      present study was to examine the effects of sipatrigine on the delayed rectifier
      currents (I(Kr) and I(Ks)), the inward rectifier current (I(K1)), the L-type Ca2+
      current (I(Ca,L)) and the fast Na+ current (I(Na)), as well as on AP duration at
      30% (APD30) and 90% (APD90) repolarization, in guinea-pig isolated ventricular
      myocytes. Each of the currents was inhibited by sipatrigine, demonstrating the
      drug to be a relatively broad-spectrum blocker of cation channels in the heart.
      However, sipatrigine was a comparatively more potent inhibitor of I(Kr) (IC50 =
      0.85 micromol/L) and I(Ks) (IC50 = 0.92 micromol/L) than of I(K1) (IC50 = 5.3
      micromol/L), I(Ca,L) (IC50 = 6.0 micromol/L) and I(Na) (IC50 = 25.5 micromol/L).
      Consistent with block of I(Kr), I(Ks) and I(K1), sipatrigine (1-30 micromol/L)
      produced a concentration-dependent prolongation of APD90. Although lower
      concentrations of sipatrigine (< or = 3 micromol/L) caused APD(30) prolongation,
      higher concentrations (> or = 10 micromol/L) shortened APD30, consistent with an
      involvement of I(Ca,L) blockade. The contrasting effects of sipatrigine on APD30
      and APD90 at higher concentrations resulted in a marked concentration-dependent
      triangulation of the AP. 5. The results of the present study demonstrate that
      sipatrigine, at concentrations previously shown to be neuroprotective in vitro,
      modulates cardiac K+, Ca2+ and Na+ currents and repolarization of the cardiac
      ventricular action potential.

PMID- 16445577
TI  - Beneficial effect of laserpitin, a coumarin compound from Angelica keiskei, on
      lipid metabolism in stroke-prone spontaneously hypertensive rats.
AB  - Recently, we found that 4-hydroxyderricin, one of the major chalcones in Angelica
      keiskei extract (an ethyl acetate extract from the yellow liquid of stems),
      suppressed increases in systolic blood pressure and reduced both serum very low
      density lipoprotein levels and liver triglyceride content in stroke-prone
      spontaneously hypertensive rats (SHRSP). In the present study, we have isolated
      laserpitin, a characteristic coumarin, from the A. keiskei extract and examined
      the effect of dietary laserpitin on blood pressure and lipid metabolism in SHRSP.
      Six-week-old male SHRSP were fed diets containing 0.1% laserpitin for 7 weeks
      with free access to the diet and water. Bodyweight gain was reduced by dietary
      laserpitin after 4 weeks through to 7 weeks without any significant change in
      daily food intake. Serum total cholesterol, phospholipid and apolipoprotein (apo)
      E levels were significantly increased, which was due to significant increases in
      cholesterol, phospholipid and apoE contents in the low- and high-density
      lipoprotein (LDL and HDL, respectively) fractions. These results suggest that
      dietary laserpitin increases serum apoE-HDL levels. In the liver, significant
      decreases in relative liver weight and triglyceride content were found after
      treatment with laserpitin for 7 weeks. An investigation of hepatic mRNA
      expression of proteins involved in lipid metabolism indicated that a significant
      decrease in hepatic triglyceride lipase may be responsible for the increase in
      serum HDL levels and also indicated that a marked decrease in adipocyte
      determination and differentiation factor 1 may be responsible, at least in part,
      for the decrease in hepatic triglyceride content. In conclusion, dietary
      laserpitin produces increases in serum HDL levels, especially apoE-HDL, and
      decreases in the hepatic triglyceride content in SHRSP.

PMID- 16445578
TI  - Differential induction of adrenomedullin, interleukins and tumour necrosis factor
      alpha by lipopolysaccharide in rat tissues in vivo.
AB  - The aim of the present study was to determine the temporal changes in tissue
      adrenomedullin (AM) and cytokine contents and cytokine and preproAM mRNA levels
      in the kidney, liver, adrenal gland and spleen of lipopolysaccharide (LPS)
      treated rats. Rats were injected with LPS (10 mg/kg, i.p.). Radioimmunoassay and
      solution hybridization-RNase protection assays were used to follow the changes in
      AM and its mRNA levels, respectively; ELISA and reverse transcription-polymerase
      chain reaction were used to follow the changes in cytokines and their mRNA
      levels, respectively. In the kidney, the preproAM mRNA levels were increased 1
      and 3 h after LPS treatment, whereas AM levels were decreased at 3 h. Interleukin
      (IL)-6 and IL-1beta levels were increased at 3 and 6 h, respectively. The
      preproAM mRNA levels were elevated in the liver 3 h after LPS injection.
      Concentrations of tumour necrosis factor (TNF)-alpha and IL-1beta were increased
      at l and 6 h, respectively. There were no changes in the levels of either
      preproAM mRNA or AM in the adrenal gland and the spleen. In the spleen, TNF-alpha
      levels were elevated at 1 and 3 h after LPS injection and IL-1beta was elevated
      at 1 and 6 h after LPS injection, whereas in the adrenal gland IL-1beta was
      elevated at 6 h after injection. The mRNA levels of the three cytokines were
      elevated at all three time intervals examined in the kidney, liver, adrenal gland
      and spleen, with the exception that TNF-alpha mRNA was not elevated in the
      adrenal gland at 6 h after LPS injection and IL-1beta mRNA was not elevated in
      the spleen at 3 and 6 h. The plasma concentrations of TNF-alpha were increased at
      1 and 3 h after LPS injection, whereas plasma concentration of IL-1beta and IL-6
      were elevated at 3 and 6 h for both. The present results suggest that the
      biosynthesis and secretion of AM may be differentially regulated in various
      tissues of rats injected with LPS and that AM may interact with cytokines during
      inflammation.

PMID- 16445579
TI  - Increased responsiveness to 5-hydroxytryptamine after antigenic challenge is
      inhibited by nifedipine and niflumic acid in rat trachea in vitro.
AB  - Antigenic challenge often induces hyperreactivity in asthmatic airway, although
      the precise mechanism(s) underlying this increased responsiveness is not entirely
      known. Tracheae obtained from ovalbumin (OVA)-sensitized saline- or OVA
      challenged rats were placed in 10 mL bath chambers for isometric recording of 5
      hydroxytryptamine (5-HT)-induced contractions. 5-Hydroxytryptamine induced a
      stronger contraction compared with control in antigen-challenged trachea under
      normal or Ca2+-free conditions. In tracheae pretreated with the L-type Ca2+
      channel blocker nifedipine (10(-6) mol/L) or the Ca2+-activated Cl- channel
      blocker niflumic acid (10(-4) mol/L), this hyperresponsiveness was not developed
      in either normal or Ca2+-free medium. The increased contractile response to 5-HT
      in allergic rat isolated trachea may be related to a greater ionic (Ca2+ and Cl-)
      channel involvement.

PMID- 16445580
TI  - Hypoxia-reoxygenation-induced apoptosis in cultured neonatal rat cardiomyocyets
      and the protective effect of prostaglandin E.
AB  - The aim of the present study was to investigate the effect of prostaglandin (PG)
      E1 on hypoxia/re-oxygenation (H/R) apoptosis and the expression of bcl-2 and bax
      in cultured neonatal rat cardiomyocytes. The H/R model was made using the first
      generation of cultured neonatal rat cardiomyocytes. Hypoxia/re-oxygenation
      apoptosis was studied by electron microscopy and agarose gel electrophoresis. The
      percentage of apoptotic cells was measured by terminal deoxyribonucleotidyl
      transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL). The expression
      of bcl-2 and bax was detected by in situ hybridization and immunohistochemical
      staining. Most cells of the H/R group tested by electron microscopy showed
      cytoplasmic concentration, nuclear chromatin condensation and margination.
      Prostaglandin E1 (5, 15 and 45 microg/L) relieved the injury. The results of DNA
      electrophoresis in the H/R group showed a typical DNA ladder and the DNA ladder
      decreased gradually corresponding with increasing doses of PGE1. The TUNEL
      staining showed that the total number of apoptotic cells in the H/R group was
      much more than that in the PGE1 (45 microg/L) group. The results of in situ
      hybridization and immunohistochemical staining showed that the bcl-2 content in
      the H/R group was lower than that in the control group; bax content showed the
      reverse. Compared with the H/R group, bcl-2 content was significantly higher in
      the PGE1 (5, 15 and 45 microg/L) groups. However, bax content in the PGE1 (5, 15
      and 45 microg/L) groups was significantly lower than that in the H/R group. 6. In
      conclusion, H/R injury can induce cardiomyocyte apoptosis. Prostaglandin E1
      obviously has anti-apoptotic effects on cardiomyocytes and the mechanisms
      probably involve the inhibition of bax expression and increased expression of bcl
      2.

PMID- 16445581
TI  - Bradykinin B2 receptor antagonism attenuates inflammation, mast cell infiltration
      and fibrosis in remote myocardium after infarction in rats.
AB  - Bradykinin may interfere with myocardial remodelling by promoting inflammation
      and mast cell activation or, alternatively, by counteracting angiotensin II
      dependent collagen accumulation. The aim of the present study was to investigate
      the role of bradykinin B2 receptor antagonism in inflammatory and mast cell
      infiltration, fibroplasia and fibrosis accumulation following myocardial
      infarction (MI). Myocardial infarction was produced by the ligature of the left
      coronary artery in male Wistar rats that were 10 weeks of age. Immediately after
      MI, rats received the B2 receptor antagonist Hoe140 (0.5 microg/kg per min, s.c.)
      or saline over a period of 3 days, 1 week or 4 weeks, constituting three separate
      groups and their respective controls. Coronal myocardial tissue sections
      underwent haematoxylin and eosin, Giemsa and picrosirius red staining, as well as
      immunohistochemistry for alpha-smooth muscle actin (SMA). Morphometric studies
      were undertaken in three different myocardial regions: MI, remote non-infarcted
      subendocardium (non-MI SE) and remote non-infarcted interventricular septum (non
      MI IVS). The MI size was comparable between Hoe140-treated groups and their
      respective controls (day 3: 42 +/- 4%, n = 8, vs 43 +/- 3%, n = 6; week 1: 37 +/-
      5%, n = 5, vs 39 +/- 2%, n = 5; week 4: 35 +/- 3%, n = 9, vs 36 +/- 3%, n = 7).
      At day 3, Hoe140 treatment reduced inflammatory cell reaction within the MI (585
      +/- 59 vs 995 +/- 170 cells/mm2; P = 0.02), non-MI SE (77 +/- 12 vs 214 +/- 57
      cells/mm2; P = 0.02) and non-MI IVS (93 +/- 16 vs 135 +/- 14 cells/mm2; P = 0.03)
      regions. Mast cells were reduced within the non-MI IVS region (0.8 +/- 0.1 vs 2.5
      +/- 0.4 cells/mm2; P = 0.006), but not within the MI region. In non-MI SE, mast
      cells were rarely found. At week 1, Hoe140 treatment reduced alpha-SMA-positive
      myofibroblast infiltration within the MI (2535 +/- 383 vs 5636 +/- 968 cells/mm2;
      P = 0.01) and non-MI SE (222 +/- 33 vs 597 +/- 162 cells/mm2; P = 0.03) regions.
      In the non-MI IVS region, alpha-SMA-positive myofibroblasts were rarely found. At
      week 4, Hoe140 treatment reduced collagen volume fraction within the MI (37 +/- 4
      vs 53 +/- 4%; P = 0.03), non-MI SE (1.3 +/- 0.2 vs 2.6 +/- 0.3%; P = 0.001) and
      non-MI IVS (1.1 +/- 0.2 vs 1.8 +/- 0.2%; P = 0.01) regions. Bradykinin promotes
      inflammation, fibroplasia and fibrosis after MI. Mast cells may have a role in
      fibrosis deposition through a bradykinin-related mechanism.

PMID- 16445582
TI  - Vasodilator actions of the endothelium-derived relaxing factor L-S
      nitrosocysteine in anaesthetized rats are markedly diminished by peroxynitrite.
AB  - The aim of the present study was to assess the effects of the potent oxidant and
      nitrating agent peroxynitrite on the haemodynamic actions of the endothelium
      derived S-nitrosothiol L-S-nitrosocysteine. The haemodynamic actions of L-S
      nitrosocysteine (12.5-100 nmol/kg, i.v.) were determined in pentobarbital
      anaesthetized rats before and after the induction of tachyphylaxis to
      peroxynitrite achieved by giving 10 intravenous injections of a 10 micromol/kg
      dose. L-S-Nitrosocysteine elicited dose-dependent reductions in mean arterial
      blood pressure and in hindquarter and mesenteric vascular resistance. The L-S
      nitrosocysteine-induced responses were substantially attenuated after
      administration of peroxynitrite. We have reported previously that nitric oxide
      mediated vasodilation is not diminished after the induction of tachyphylaxis to
      peroxynitrite. Taken together, these findings support the concept that
      peroxynitrite reduces the vasodilator actions of L-S-nitrosocysteine via
      oxidation and/or nitration of putative membrane-bound S-nitrosothiol recognition
      sites.

PMID- 16445583
TI  - Neurological Effects of White Spirit: Contribution of Animal Studies during a 30
      Year Period*.
AB  - Numerous studies have suggested that long-term occupational exposure to white
      spirit may cause chronic toxic encephalopathy (WHO 1996). This review summarizes
      the chronic nervous system effects of white spirit in animal studies during a 30
      year period. First, routine histopathology was consistently unable to reveal
      adverse peripheral or central nervous system effects after inhalation of white
      spirit. Second, neurobehavioural studies in animals showed no adverse effect
      after inhalation of white spirit with a high content of aromatics in contrast to
      what was found with products with a low content. Third, white spirit with a high
      content of aromatics induced adverse neurochemical changes at inhalation of 400
      ppm and possibly already at 100 ppm. In the studied parameters, white spirit with
      a low content of aromatics showed no clear adverse neurochemical effects at
      inhalation of 400 ppm, but the neurophysiological tests showed adverse effects at
      this level. Fourth, neurophysiological methods may be more sensitive than
      histopathological, neurobehavioural and neurochemical methods. Overall, white
      spirit with a high and a low content of aromatics showed no overt difference in
      long-term effects in animals, taking all studied end-points into account. The
      differences in sensitivity of the test methods should be taken into consideration
      if new toxicological studies are conducted on this type of solvents.

PMID- 16445584
TI  - The endocannabinoid system: current pharmacological research and therapeutic
      possibilities.
AB  - In the relatively short period of time since the discovery of cannabinoid
      receptors and their endogenous ligands, the endocannabinoids, an intensive
      research effort has resulted in the identification of agents that affect all
      aspects of the endocannabinoid system. The cannabinoid(1) receptor antagonist
      rimonabant is in phase III clinical trials for the treatment of obesity and as an
      aid to smoking cessation, and cannabinoid(2) receptor agonists are promising in
      animal models of inflammatory and neuropathic pain. In the present MiniReview,
      the endocannabinoid system is described from a pharmacological perspective. The
      main topics covered are: the mechanism of action of cannabinoid(2) receptor
      agonists; identification of the endocannabinoid(s) involved in retrograde
      signalling; the elusive mechanism(s) of endocannabinoid uptake; therapeutic
      possibilities for fatty acid amide hydrolase inhibitors; and the cyclooxygenase-2
      and lipoxygenase-derived biologically active metabolites of the endocannabinoids.

PMID- 16445585
TI  - Hepatoprotection of D-galactosamine-induced toxicity in mice by purified
      fractions from Garcinia kola seeds.
AB  - The hepatoprotective effect of a biflavonoid complex, kolaviron, and its
      fractions from Garcinia kola seeds, together with the possible mechanisms
      involved was investigated in mice intoxicated with a single dose of D
      galactosamine (GalNH(2)). Likewise, the ability of vitamin E to attenuate the
      toxicity was examined. Kolaviron, was separated by thin-layer chromatographic
      technique into three fractions; Fraction I, Fraction II and Fraction III with RF
      values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron,
      fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days
      before challenge with a single dose of GalNH(2) (800 mg/ kg) significantly
      (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by
      67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH(2)-only intoxicated
      mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH(2)
      induced increase in the activities of these enzymes. In addition, pretreatment
      with kolaviron and fraction II significantly (P<0.05) decreased the activity of
      microsomal gamma-glutamyl transferase (gamma-GT) by 42% and 46%, respectively.
      Administration of kolaviron to GalNH(2)-intoxicated mice also restored glucose-6
      phosphatase to level that was comparable to the control (P<0.05). These extracts
      except fraction III prevented the accumulation of serum and microsomal lipid
      peroxidation products, and also prevented the depletion of reduced glutathione
      (GSH) levels in the liver of GalNH(2)-intoxicated mice. Kolaviron, fraction I and
      fraction II at a dose of 100 mg/kg caused an induction of glutathione-S
      transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT)
      activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH(2)-induced
      toxicity was essentially prevented as indicated by a liver histopathologic study
      of liver slices from mice pretreated with kolaviron, fraction I and fraction II.
      This study shows that treatment with kolaviron, fraction I and fraction II
      (purified fractions from Garcinia kola) appeared to enhance the recovery from
      GalNH(2)-induced hepatotoxicity, and that the fractions I and II may therefore be
      responsible for the observed antihepatotoxic effect of kolaviron. This protection
      may be due to the ability of these extracts to induce the expression of phase II
      drug metabolizing enzymes.

PMID- 16445586
TI  - Functional characterization of serotonin receptor subtypes in human duodenal
      secretion.
AB  - Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the
      sensitivity for 5-HT might be altered in dyspeptic patients infected with
      Helicobacter pylori. The purpose of the present study was to characterize the 5
      HT-induced electrogenic ion transport in the duodenum of dyspeptic patients with
      or without Helicobacter pylori infection, and to determine the 5-HT receptor
      subtypes functionally involved. Biopsies from the second part of duodenum were
      obtained from 43 dyspeptic patients during routine endoscopy. Biopsies were
      mounted in modified Ussing chambers with air suction for measurements of short
      circuit current by a previously validated technique. Short-circuit current was
      measured before and after application of graded cumulative doses of 5-HT and a
      single dose of bumetanide (an inhibitor of chloride/bicarbonate transport), or
      one of the selective 5-HT receptor antagonists: ketanserin, ondansetron, or SB
      204070 (1-butyl-4 piperidinmethyl-8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5
      carboxylate HCl). Histological examination was performed on duodenal biopsies.
      Helicobacter urease testing and histological examination determined Helicobacter
      pylori infection. 5-HT induced a dose-dependent and bumetanide-sensitive short
      circuit current, which was independent of the presence of Helicobacter pylori
      infection. All the three 5-HT receptor antagonists failed to significantly effect
      basal and 5-HT-induced short-circuit current. Our results indicate that in human
      duodenum 1) 5-HT is a potent stimulator of bumetanide-sensitive secretion, 2) the
      serotonergic receptor subtype, which acts as the main mediator of 5-HT-induced
      secretion is different from the 5-HT(2), 5-HT(3), and the 5-HT(4) subtype and, 3)
      the sensitivity to 5-HT is not altered by Helicobacter pylori infection.

PMID- 16445587
TI  - Investigation of the effect of hyperbaric oxygen on experimental cyclosporine
      nephrotoxicity.
AB  - Hyperbaric oxygen interacts with drugs which patients use concurrently with
      hyperbaric oxygen treatment, which may cause in potentiation or inhibition of
      both therapeutic and toxic effects. We examined the effect of hyperbaric oxygen
      therapy on experimental cyclosporine A nephrotoxicity. The study comprised four
      groups of rats: a control group, a cyclosporine A group (25 mg/kg/day
      intraperitoneally for four days), a hyperbaric oxygen group (60 min. every day
      for four days at 2.5 atmospheric pressure), and a cyclosporine A+hyperbaric
      oxygen group (CsA 25 mg/kg/day intraperitoneally for four days+hyperbaric oxygen
      for 60 min. every day for four days at 2.5 atmospheric pressure). Hyperbaric
      oxygen did not alter biochemical parameters. Cyclosporine A increased serum urea
      and serum creatinine levels and decreased creatinine clearance. In the
      cyclosporine A+hyperbaric oxygen group serum urea level increased more than in
      the cyclosporine A group. Cyclosporine A increased tubular epithelial cell
      apoptosis and necrosis score values. The numbers of apoptotic cells in proximal
      tubule epithelial cells in the cyclosporine A+hyperbaric oxygen group were
      significantly higher than those of the cyclosporine A group. We recommend that
      renal functions of the patients receiving cyclosporine A should be monitored
      during hyperbaric oxygen therapy.

PMID- 16445588
TI  - Effect of chromium picolinate on modified forced swimming test in diabetic rats:
      involvement of serotonergic pathways and potassium channels.
AB  - Depression occurs frequently in patients with diabetes mellitus. Chromium
      picolinate, an essential trace element is recommended for diabetes and also has
      been reported to benefit depression, but its mechanism is still debated. To
      investigate the mechanism, we studied its effects on serum insulin, serum glucose
      and on modified forced swimming test, a behavioural paradigm for depression in
      rats. The study involving co-administration of sub-active doses of glimepiride, a
      K(+) channel blocker and chromium picolinate on blood glucose levels and modified
      forced swimming test was also performed to probe any role of K(+) channels in its
      antidiabetic and antidepressants effects. Streptozotocin (55 mg/kg,
      intraperitoneally) was injected in rats to induce diabetes (Type 1). After a
      week, chromium picolinate (8 microg/ml in drinking water) was administered for 4
      weeks. Normal rats received similar drug treatment. The sub-active doses of
      chromium picolinate (4 microg/ml in drinking water) and glimeperide (2.5 mg/kg,
      orally) were co-administered and their effects on modified forced swimming test
      and on glucose levels were measured. Chromium picolinate (8 microg/ml in drinking
      water) produced hypoglycaemia in diabetic and normal rats. It had no effects on
      the streptozotocin-induced reduction in insulin levels. Chromium picolinate (8
      microg/ml in drinking water) increased swimming with subsequent decrease in
      immobility. The sub-active doses of chromium picolinate and glimeperide showed
      significant additive effects in modified forced swimming test and reduction in
      serum glucose concentrations, though statistically insignificant. In conclusion
      chromium picolinate shows antidepressant action on modified forced swimming test
      affecting only swimming that suggests serotonergic pathways involvement. The
      additive effects on swimming in modified forced swimming test and reduction in
      serum glucose levels shows involvement of K(+) channels in antidiabetic and
      antidepressant actions of chromium picolinate.

PMID- 16445589
TI  - Dual effect of flurbiprofen on cell proliferation and agonist-induced Ca(2+)
      movement in human osteosarcoma cells.
AB  - In human MG63 osteosarcoma cells, the effect of flurbiprofen on intracellular
      Ca(2+) concentrations ([Ca(2+)](i)) and proliferation was explored. The
      proliferation was enhanced by 20-120 microM flurbiprofen, and was decreased by
      140-200 microM flurbiprofen. The effect of flurbiprofen on the increases in
      cytosolic free Ca(2+) levels ([Ca(2+)](i)) induced by ATP, bradykinin, histamine
      and thapsigargin (an inhibitor of the endoplasmic reticulum Ca(2+) ATPase), was
      examined. In cell preincubated with 20 or 80 microM flurbiprofen, the [Ca(2+)](i)
      increases induced by all agonists were attenuated. In the presence of 20 microM
      flurbiprofen, the decreased [Ca(2+)](i) responses with the agonists were
      attributed to a defective Ca(2+) influx because this decrease was unobserved in
      agonists-induced [Ca(2+)](i) increases in the absence of extracellular Ca(2+). In
      the presence of 80 microM flurbiprofen, both the Ca(2+) influx component and the
      Ca(2+) releasing (from organelles) component were defective. These results
      suggest that flurbiprofen could alter proliferation and inhibit [Ca(2+)](i)
      increases.

PMID- 16445590
TI  - Effects of methylated derivatives of Luteolin isolated from Cyperus alopecuroides
      in rat H4IIE hepatoma cells*.
AB  - Polyphenols are ubiquitous substances in human diet. Their antioxidative,
      antiinflammatory and antiviral effects are of interest for human health, and
      polyphenols such as luteolin are used at high concentrations in food supplements.
      Luteolin is metabolized to glucuronides, but also to methylated derivatives. For
      example, O-methylation of the catechol group mediated by the catechol-O-methyl
      transferase, is an important step in flavonoid metabolism. The aim of this
      project was to determine the effect of O-methylation on antioxidative capacity
      and cytotoxicity of luteolin in H4IIE rat hepatoma cells. Therefore we analyzed
      the effects of luteolin 5,3'-dimethylether, isolated from the flowers of foxtail
      flatsedge (Cyperus alopecuroides) and luteolin 5,7,3',4'-tetramethylether
      compared to the non-methylated flavonoid luteolin. The antioxidative potential of
      luteolin was lowered by methylation, an effect that seems to be mediated by
      masking of the catechol moiety in the B ring. The cytotoxic potential of luteolin
      5,3'-dimethylether is comparable to luteolin, but the tetramethylether showed no
      cytotoxic effect. The cytotoxic effect of luteolin but not luteolin 5,3'
      dimethylether was mediated via apoptosis (caspase-3 activation). We conclude that
      the O-methylation of luteolin led to a decreased radical-scavenging activity and
      to a reduction in the apoptotic potential of the flavonoid.

PMID- 16445591
TI  - Effect of sodium bicarbonate in rats acutely poisoned with dichlorvos.
AB  - The development of effective antidotes against organophosphates such as
      dichlorvos has been a persistent challenge over the past decades. Therapy of
      organophosphate poisoning is based on the administration of atropine and oxime as
      standard antidotes. The present study was undertaken to evaluate the ability of
      sodium bicarbonate to improve protective effects of standard antidotes in rats
      poisoned with dichlorvos. The aim of this experiment was to establish the
      correlation between protective effects and biochemical parameters relevant for
      acid-base status. In order to examine the protective effect of both standard
      antidotes and their combinations, groups of experimental animals were poisoned
      subcutaneously with increasing doses of dichlorvos. Immediately thereafter, rats
      were treated with atropine 10 mg/kg intramuscularly, oximes 10 mg/kg
      intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally. These
      antidotes were administered either as single doses or in combinations. In the
      biochemical part of the experiments, rats were poisoned with dichlorvos 1.3
      LD(50) (10.64 mg/kg) subcutaneously and immediately thereafter treated with
      atropine 10 mg/kg intramuscularly, oximes (trimedoxime or obidoxime) 10 mg/kg
      intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally either as
      single doses or in combinations. Parameters relevant for acid-base status were
      measured 10 minutes after the administration of antidotes. The results of our
      study indicate that addition of sodium bicarbonate to standard antidotes
      significantly improves protective effects of atropine, obidoxime and trimedoxime.
      Correlation between protection and biochemical outcome is clearly evident when
      sodium bicarbonate is being added to atropine.

PMID- 16445592
TI  - Effects of premedication medicines on the formation of the CYP3A4-dependent
      metabolite of ropivacaine, 2', 6'-Pipecoloxylidide, on human liver microsomes in
      vitro.
AB  - Ropivacaine is a relatively new amide-type local anaesthetic, mainly used for
      surgery and postoperative pain relief. In this study we have investigated the
      interaction between the CYP3A4 metabolite of ropivacaine, 2',6'-pipecoloxylidide
      (PPX), and premedication with, i.e., psychotropic and antianxiety agents
      (diazepam, midazolam), hypnotics (thiamylal), local anaesthetics (lidocaine),
      depolarizing muscular relaxants (vecuronium), antihypertensive (clonidine) and
      H(2)-receptor antagonist (cimetidine) using human liver microsomes in vitro. The
      effects of the interaction between PPX and premedications were examined using a
      human liver microsomal preparation in vitro. The concentrations of ropivacaine
      and PPX were determined by HPLC with UV detection. The apparent Michaelis-Menten
      constant (Km) and the maximal velocity of total metabolic formation (V(max)) of
      PPX, the main metabolite of ropivacaine in human liver microsomes, were 17.7
      (microM, mean) and 711 (nmol/min./mg protein, mean), respectively. Five
      premedications (diazepam, lidocaine, cimetidine, vecuronium and clonidine) did
      not inhibit ropivacaine metabolism in human liver microsomes at concentrations
      within the therapeutic range. However, midazolam and thiamylal weakly inhibited
      ropivacaine metabolism in competitive manner (IC(50) 7.8 microM and 250 microM,
      respectively). The results show lack of interaction between ropivacaine and seven
      premedication medicines within the therapeutic range of ropivacaine using human
      liver microsomes in vitro.

PMID- 16445593
TI  - Efficacy of immediate and subsequent therapies against soman-induced seizures and
      lethality in rats.
AB  - The purpose of the present study was to examine the efficacy of a triple
      combination of drugs with adequate anticonvulsant effects and a dual combination
      with inadequate anticonvulsant effects followed by adjunct therapy. The results
      showed that combined intramuscular injections of HI-6 (42 mg/kg), atropine (14
      mg/kg), and avizafone (3 mg/kg) administered 1, 16, and 31 min. after exposure to
      a soman dose of 4 x LD(50) completely terminated seizures with a moderate
      mortality rate (25%). When the soman dose was lowered to 3 x LD(50) the
      anticonvulsant effect was complete, and no rats died within 24 hr. Rats
      challenged with 5 x LD(50) of soman all died within 10 min. Without avizafone in
      the combination, seizures induced by 3 or 4 x LD(50) of soman could not be
      terminated unless an adjunct therapy consisting of procyclidine (6 mg/kg),
      diazepam (10 mg/kg), and pentobarbital (30 kg/kg) was given, and the mortality
      rate was comparatively high (78%). Administration of the adjunct therapy alone 6
      16 min. after 4 x LD(50) of soman stopped the seizure activity, but all the rats
      died within 24 hr. Marked neuropathology was found in the piriform cortex and
      amygdala, whereas the hippocampal CA1 field was effectively protected when both
      the triple combination and the dual combination plus adjuncts had stopped
      seizures 35-55 min. after onset. It is concluded that termination of soman
      induced seizures at an early stage (<20 min.) is crucial to avoid neuronal
      pathology.

PMID- 16445594
TI  - Protective effect of green tea extract and tea polyphenols against FK506-induced
      cytotoxicity in renal cells.
AB  - The nephrotoxicity induced by the immunosuppressive drug FK506 (tacrolimus or
      fujimycin), limits its usefulness in widespread application, and the underlying
      mechanism has not been completely understood. The primary targets of FK506 in the
      kidney are the proximal tubular epithelial cells. In this study, the protection
      of green tea extract against FK506-induced cell death of LLC-PK1 cells was
      investigated. FK506 caused a significant decrease in survival of the cells, but
      the addition of green tea extract reduced this effect in a dose-dependent manner.
      Treatment of the cells with 50 microM (41.1 microg/ml) FK506 induced a
      significant increase in annexin V-positive/propidium iodide-negative cells from
      2.68 to 14.5%, whereas the addition of 6.25, 12.5, and 25 microg/ml of green tea
      extract caused a significant protective effect in apoptotic cells from 14.5 to
      6.51, 3.20 and 3.02%, respectively. The effect of five different constituent tea
      polyphenols was also examined. Epigallocatechin-gallate and epigallocatechin
      significantly reduced FK506-induced cytotoxicity but epicatechin and catechin had
      no effect on cell viability. Furthermore, changes in cytochrome c release and
      caspase activation, which characterize apoptosis, were studied. Epigallocatechin
      gallate and epigallocatechin suppressed a significant release of cytochrome c and
      activation of caspase-3 in FK506-treated LLC-PK1 cells.

PMID- 16445595
TI  - Inhibitory effect of 5-fluorouracil on cytochrome P450 2C9 activity in cancer
      patients.
AB  - Drug interactions have been reported between 5-fluorouracil and cytochrome P450
      2C9 (CYP2C9) substrates, S-warfarin and phenytoin. This study was performed to
      determine the influence of 5-fluorouracil on cytochrome P450 2C9 (CYP2C9)
      activity in colorectal cancer patients (n=17) receiving 5-fluorouracil. Losartan
      was used as a marker to assess CYP2C9 activity. Losartan and its CYP2C9 dependent
      metabolite, E-3174, were determined in urine. The ratios of urinary losartan/E
      3174 before and after the 5-fluorouracil treatment were compared for each
      patient. Genotyping was performed to detect the CYP2C9*2 and CYP2C9*3. At the end
      of the first cycle of 5-fluorouracil, losartan/E-3174 ratio was increased by
      28.0% compared to the pre-treatment values (P=0.15). In five patients recruited
      for phenotyping after three 5-fluorouracil cycles, the metabolic ratio was
      increased significantly by 5.3 times (P=0.03). The results suggest that in most
      patients 5-fluorouracil inhibited CYP2C9 activity. This inhibition was more
      pronounced when the total administered dose increased. This finding may help
      explain the mechanism of interaction between 5-fluorouracil and CYP2C9
      substrates.

PMID- 16445596
TI  - Multi-modal and tissue-differentiated experimental pain assessment:
      reproducibility of a new concept for assessment of analgesics.
AB  - Experimental pain models for assessment of analgesic effect needs to be
      reproducible, valid and responding in a uniform way to changes in pain level. The
      pain system differs in various tissue types and analgesics may have different
      effects in different tissues. This study assessed the reproducibility of an
      experimental model using mechanical, thermal and electrical stimulations. Pain
      was evoked in three tissues: Skin, muscle and viscera. Pain was evoked and
      assessed in 24 healthy volunteers. The experiment was repeated three times with
      30 min. intervals and twice with a weekly interval. Systematic bias, intra-class
      correlation (ICC) and coefficient of variation (CV) and valid sample sizes for
      analgesic testing were assessed. The model proved to be feasible. Most tests were
      unbiased, showing stable means except for the mechanical and thermal stimulation
      in viscera, which showed decreasing pain thresholds when the tests were repeated
      with 30 min. intervals. Generally the pain tests showed relatively high CV (mean
      71%, range 8-145%). The pain tests showed high ICC's (>0.80) when repeated on the
      same day. When the tests were repeated with an interval of one week, ICC was
      smaller (mean 0.79 range 0.49-0.96). This means that these tests are useful for
      analgesic testing recruiting useful sample sizes in a crossover (mean 31 range 2
      84) and a parallel study (mean 59 range 3-164) design. Application of this
      experimental pain model in a cross-over study design with appropriate base-line
      recordings offers a unique opportunity of revealing analgesic effects on pain
      arising from different tissues.

PMID- 16445597
TI  - Drug-related visits to a district hospital emergency room.
AB  - The role of adverse drug reactions (ADRs) as a cause of hospital visits varies
      depending on the type of hospitals. Our aim was to determine the incidence of
      drug-related emergency department visits to a district hospital, and to identify
      the drugs and patient groups involved. All patient visits to the emergency
      department of a Finnish district hospital were evaluated prospectively for 6
      months. The physician on duty and a clinical pharmacologist selected all possibly
      drug-related visits for further scrutinising. The causality assessment (drug
      related or not) was judged according to WHO criteria, based on the patients'
      files, including laboratory and other data. Of the 7113 evaluated visits, 167
      (2.3%) were "certainly" or "probably" drug-related; 102 (1.4% of all) were
      related to ADRs and 65 (0.9%) to intentional overdoses. The most common ADRs were
      gastrointestinal symptoms (n=17) caused by antibiotics, opioids, nonsteroidal
      antiinflammatory or cytostatic drugs. The International Classification of Disease
      (ICD-10) codes on patients' files were insensitive to disclose ADRs. The ADR
      patients were older (mean age 57 years) than the intentional overdose patients
      (38 years; P<0.001). Males predominated in the intentional overdose group (38
      males, 27 females) but not in the ADR patients. The majority of intentional
      overdoses was caused by psychotropics. The ADRs lead to hospitalisation in a
      higher frequency (51%) than did the intentional overdoses (35%). In conclusion,
      the incidence of "certainly" or "probably" drug-related visits to the district
      hospital emergency room was relatively low. The ICH-10 codes on patients' files
      were found to be insensitive to disclose the ADRs, even when they lead to
      hospital admission, casting doubts on the usefulness of ICH codes alone in ADR
      evaluation.

PMID- 16445598
TI  - Pain perception after subcutaneous injections of media containing different
      buffers.
AB  - Several hormones are administered by daily subcutaneous injections. Pain caused
      by subcutaneous injection is an unpleasant condition, which can limit patient
      compliance. The objective of the present study was to evaluate the perception of
      pain by subcutaneous injection of two different and commercially available
      solutions for dispensing recombinant human growth hormone. The solutions are
      characterised by pH, conservation, and buffer. Isotonic saline was used as
      reference solution. Fifty-four healthy volunteers (mean age (+/-S.E.M.): 35.5+/
      1.1 years) were recruited to the double-blind, randomised study. All injections
      were performed pairwise (right and left thigh) in one day by the same experienced
      nurse. Perception of pain was evaluated by the volunteers immediately after
      injection and 2 min. after injection into the thigh of three formulations, which
      differed with respect to pH and buffers (histidine, citrate and saline,
      respectively). Significantly more participants (38/54) found than the citrate
      buffer caused more pain than the histidine buffer immediately after injection
      (P=0.002). Histidine buffer did not cause more pain than saline (P=0.996). After
      2 min., there was no difference between the histidine and the citrate buffer
      (P=1.00), nor between the histidine buffer and saline (P=1.00). In summary, the
      solution-containing citrate as buffer caused more pain after subcutaneous
      injection than the solution with histidine as buffer. Considering patient
      compliance, it seems advisable to employ histidine-buffered solution rather than
      citrate-buffered solution for dispensing recombinant human growth hormone by
      daily subcutaneous injections.

PMID- 16445599
TI  - Accidental ten times overdose administration of recombinant human erythropoietin
      (rh-EPO) up to 318,000 units a day in acute myocardial infarction: report of two
      cases.
AB  - The cytokine erythropoietin protects the heart from ischaemic injury, in part by
      preventing apoptosis. But appropriate dose of erythropoietin for the protection
      of injured heart has not been studied. While we were researching the cardiac
      protective effects of erythropoietin in acute myocardial infarction, we
      experienced two cases of accidental nearly ten times overdose administration of
      erythropoietin up to 318,000 units instead of 33,000 units on the second day of
      three scheduled days of treatment. So a total of 384,000 units of erythropoietin
      were administered during three days. In case 1, the ALT level soared up to 386
      U/l on the second day of administration and decreased slowly. It was back to
      normal state 3 months later. The AST level increased slowly up to 391 U/l and
      normalized 3 months later. Haemoglobin level was elevated up to 15.7 g/dl (14.7
      g/dl at admission) and, 3 months later, normalized to 14.8 g/dl. In case 2, the
      ALT level was elevated up to 98 U/l on the second day of administration and
      decreased slowly. Three months later, the ALT level was normalized. The AST level
      also increased slowly up to 71 U/l and normalized 3 months later. Haemoglobin
      level was elevated up to 15.6 g/dl (13.8 g/dl at admission) and, 3 months later,
      normalized to 13.6 g/dl. In these two cases reported, these patients, even after
      massive overdose, tolerated it relatively well and the only side-effects we found
      were elevated liver enzyme and haemoglobin levels.

PMID- 16445600
TI  - Contrasting changes in phase I and phase II metabolism of acetaminophen in male
      mice pretreated with carbon tetrachloride.
AB  - Effect of carbon tetrachloride (CCl(4)) pretreatment on the biotransformation and
      elimination of acetaminophen were examined in male mice. A 24 hr initial dose of
      CCl(4) (0.05 ml/kg, intraperitioneally) reduced the induction of hepatotoxicity
      resulting from acetaminophen treatment (350 mg/kg, intraperitoneally) as
      determined by changes in serum alanine and aspartate aminotransferase, and
      sorbitol dehydrogenase activities. Acetaminophen and the major metabolites in
      plasma were monitored for 12 hr following acetaminophen treatment. CCl(4)
      pretreatment decreased the plasma concentrations of acetaminophen-cysteine and
      acetaminophen-mercapturate, but acetaminophen-glucuronide and acetaminophen
      sulfate were increased significantly. The elimination of the parent drug from
      plasma was not affected by CCl(4). In urine collected for 24 hr, the
      concentrations of acetaminophen-sulfate and acetaminophen-glucuronide were
      increased by 84% and 33%, respectively, whilst acetaminophen-cysteine and
      acetaminophen-mercapturate were reduced to approximately one third of control.
      Expression of cytochrome P450 (CYP) isozymes was determined using antibodies of
      2E1 and 1A2 as probes. CYP2E1 and 1A2 expressions were decreased significantly by
      CCl(4). Likewise, CCl(4) treatment reduced the microsomal p-nitrophenol
      hydroxylase and p-nitroanisole O-demethylase activities to less than one third of
      control. The results indicate that, although CCl(4) reduces the generation of
      thioether conjugates of acetaminophen by decreasing the CYP activities,
      inhibition of the oxidative metabolism of acetaminophen is counterbalanced by the
      enhancement of conjugate formation via the glucuronide and sulfate pathways,
      resulting in elimination of the drug at a rate equivalent to that in normal mice.
      It is suggested that liver injury in patients may not warrant a mandatory
      reduction of drug doses extensively inactivated via phase II reactions.

PMID- 16445601
TI  - Pretreatment with tamoxifen does not change acute epirubicin cardiotoxicity in
      rats.

PMID- 16445602
TI  - Difficult clinical decisions in gynecological oncology: identifying priorities
      for future clinical research.
AB  - This study investigates the acceptability and feasibility of conducting
      randomized controlled trials (RCTs) in gynecological oncology by ascertaining the
      views of the Australian Society of Gynaecologic Oncologists (ASGO) about
      important clinical questions in this field, current treatment preferences, and
      willingness to participate in trials to address these questions. Members of ASGO
      received a mailed survey. Thirty-one gyneoncologists participated in this study
      (79% response fraction). There was considerable support for an RCT (81%; 95%
      confidence interval [CI], 63-93%) to compare sentinel node biopsy with total
      groin dissection for women with vulval cancer. This clinical question was also
      rated as "extremely" or "very" important by 91% (95% CI, 74-98%) of respondents,
      who also indicated high levels of individual equipoise. Another priority for
      research involved the use of second-line chemotherapy for women who have rising
      CA125 titers. This clinical question was rated as extremely or very important by
      71% (95% CI, 52-86%), exhibited high levels of individual equipoise, with 74%
      (95% CI, 55-88%) of respondents willing to participate in an RCT to address this
      issue. The conduct of surveys of representative groups of clinicians provides
      useful empirical data to focus clinical research efforts where they are most
      likely to be successful based on equipoise, feasibility, and clinical interest.

PMID- 16445603
TI  - Ovarian cancer in pregnancy: a clinicopathologic analysis of 22 cases and review
      of the literature.
AB  - The aim of this study was to summarize our experience of ovarian cancer diagnosed
      during pregnancy, to review the literature concerned, and to discuss the
      rationale for therapy. Twenty-two patients of ovarian malignancies complicating
      pregnancy were treated at Peking Union Medical College Hospital between 1985 and
      2003. Data on treatment and follow-up were reviewed, and their outcomes were
      analyzed by survival analysis. The incidence of ovarian carcinoma complicating
      pregnancy in the series was 0.073/1000 pregnancies. Nine (40.9%) were found with
      ovarian malignant germ cell tumors, six (27.3%) with low malignant potential
      tumors, five (22.7%) with invasive epithelial tumors, and two (9.1%) with sex
      cord stromal tumors. Sixteen (72.7%) of the patients were diagnosed in stage I
      and had achieved complete remission. Four of the five in advanced stage died.
      Ascites presenting at diagnosis implies advanced disease and gloomy prognosis.
      The mean follow-up was 47.8 months. The prognosis was significantly related with
      stage and histologic type (P < 0.05). Thirteen healthy live babies were recorded
      in this group, and one premature newborn died of respiratory distress syndrome.
      The clinical characters and prognosis of ovarian cancers complicating pregnancy
      are similar to those of nonpregnant, reproductive-age women. Management depends
      on histology of the tumor, stage of the tumor, and the term of the pregnancy. In
      most of cases, conservative surgical treatment could be performed with adequate
      staging and debulking equal to the treatment of nonpregnant women. Chemotherapy
      is not contraindicated during the second or third trimester, but the choice of
      couple must be considered.

PMID- 16445604
TI  - Gonadotropins and ovarian carcinogenesis: a new era of basic research and its
      clinical implications.
AB  - The possible relationship between gonadotropins and ovarian carcinoma development
      has received much attention, and in recent years, great progress has been made in
      basic and epidemiologic research about this issue. Gonadotropins sensitivity in
      the ovarian surface epithelium (OSE) and in a subset of ovarian carcinomas has
      been established in vivo and in vitro. Gonadotropins have been shown to induce
      various biologic actions in the OSE and ovarian carcinoma cells, such as changes
      in cell proliferation, apoptosis, cell adhesion, and chemosensitivity. These
      basic studies strongly suggest that gonadotropins are involved in the development
      and progression of ovarian carcinoma. In contrast, although earlier studies
      showed a significant risk of infertility therapy for ovarian carcinoma
      development, subsequent studies reported only slightly increased or no
      significant increased risk of gonadotropin stimulation and/or assisted
      reproductive technologies for ovarian carcinoma development. Therefore, the
      association between ovarian stimulation and ovarian carcinoma remains
      controversial. Nevertheless, since development of ovarian carcinoma in infertile
      women during infertility treatment is a serious concern for gynecologists, this
      review also covers important points for clinical practice, especially the issue
      of early detection of ovarian carcinoma.

PMID- 16445605
TI  - Primary peritoneal carcinoma: experience with cytoreductive surgery and
      combination chemotherapy.
AB  - The objective of this study was to review the clinical outcome and prognosis of
      patients with primary peritoneal carcinoma (PPC) treated with cytoreductive
      surgery and combination chemotherapy. We retrospectively reviewed the charts of
      27 patients with histologically confirmed PPC, treated between March 1990 and
      February 2004 at Asan Medical Center, South Korea. The review included
      demographic data, pathologic findings, treatments, and outcomes. The mean age of
      the 27 patients was 57.5 +/- 7.2 years, and the rate of optimal cytoreduction was
      70.4%. Seven patients had stage IIIB, 17 had stage IIIC, and 3 had stage IV; all
      patients received adjuvant chemotherapy. There were 4 patients with progressive
      disease, 5 partial responders, and 15 complete responders; the remaining 3
      patients were nonevaluable. At the time of the review, 10 patients were alive
      without evidence of disease, 3 were alive with disease, and 14 had died from
      disease. The median overall survival time was 41 months, and the overall 5-year
      survival rate was 18.1%. Patients who had optimal cytoreduction had a longer
      median survival (42 months) than those who had suboptimal cytoreduction (10
      months; P < 0.05). Combination chemotherapy after optimal cytoreductive surgery
      may be effective in the treatment of patients with PPC.

PMID- 16445606
TI  - A 10-year review of primary fallopian tube cancer at a community hospital: a high
      association of synchronous and metachronous cancers.
AB  - Primary fallopian tube carcinomas (PFTC) are rare gynecological tumors
      infrequently diagnosed prior to operative intervention. A retrospective review
      was performed to characterize the distribution and clinicopathologic significance
      of these tumors. Identification of PFTC was achieved through a review of the
      tumor registry and medical record ICD-9 codes at a community teaching hospital. A
      total of 1.5% of all gynecological cancers were PFTC. Most patients were presumed
      to have ovarian cancer. Ultrasound had the highest sensitivity (82%) for
      preoperative diagnosis. Surgical exploration was needed for definitive diagnosis
      in all patients. Optimal debulking was predictive of survival and of a negative
      second-look laparotomy (P < 0.05). Twenty-five percent of patients had a
      metachronous cancer diagnosed prior to their fallopian tube cancer, and 22% had a
      synchronous gynecological malignancy diagnosed at the time of surgical
      exploration. The response rate to platinum-based chemotherapy was 78%. The 5-year
      survival rate was 87%, and the overall survival rate was 75%. The median follow
      up was 38 months. This report details the diagnostic and therapeutic experience
      of patients with PFTC and describes the occurrence of synchronous and
      metachronous gynecological cancers.

PMID- 16445607
TI  - Sampling the omentum in ovarian neoplasia: when one block is enough.
AB  - Infracolic omentectomy should be performed on all patients as part of the
      surgical management of suspected ovarian neoplasia to allow accurate pathologic
      staging. Unlike the primary ovarian lesion, no guidelines exist as to how the
      pathologist should sample the omentum. We retrospectively examined pathology
      reports from 692 cases of primary ovarian neoplasia and demonstrated a high
      positive predictive value for omenta described as macroscopically involved
      (98.4%). We propose a system of sampling omenta in which block taking is
      minimized in cases where the ovary appears benign and the omentum normal or where
      the ovary appears malignant and correspondingly the omentum appears involved.
      Thorough sampling should be focused on those cases where the ovary appears
      malignant or borderline and the accompanying omentum normal. This will allow a
      reduction in departmental workload without a reduction in quality of pathologic
      staging.

PMID- 16445608
TI  - A decreasing incidence of ovarian carcinoma in Israel.
AB  - The aim of the present study was to assess the incidence trend of invasive
      epithelial ovarian carcinoma in Israel. We assessed the incidence rate of
      invasive epithelial ovarian cancer in Israeli Jewish women during the 10-year
      period from 1993 to 2002 based on data obtained from the population-based Israel
      National Cancer Registry. There was a gradual significant decrease in the
      incidence of ovarian cancer from 9.64 in 1993 to 6.55 in 2002. The decrease in
      incidence was evident in all ethnic groups except those born in Asia and in all
      the age groups older than 35 years. The decrease in incidence of ovarian
      carcinoma is gratifying, but its reason remains obscure.

PMID- 16445609
TI  - Comparison of diagnostic usefulness of predictive models in preliminary
      differentiation of adnexal masses.
AB  - The purpose of this study was to compare prognostic models evaluating the
      probability of an ovarian cancer occurrence based on a number of clinical and
      ultrasonographic data in women with adnexal masses. A total of 686 women with
      adnexal masses underwent the examinations between 1994 and 2002. The recorded
      parameters included: age, menopausal status, body mass index, the grayscale and
      Doppler ultrasonographic examination, and selected markers concentration levels.
      In order to find the best combination of features, which significantly influences
      the probability of malignancy, stepwise logistic regression analysis, as well as
      artificial neural network, was used. The diagnostic efficiency of received models
      was estimated and compared using receiver-operating characteristics (ROC) curve.
      The results indicate that 431 and 255 patients had a benign and malignant ovarian
      tumor, respectively. Application of stepwise logistic regression analysis
      revealed statistically significant importance of eight features. The sensitivity
      and specificity for the received model were 65.71% and 77.59%, respectively.
      Three-layer perceptron network shows 13 features as significant predictors of
      malignancy. The network gave a sensitivity of 85.7% and specificity of 93.1%.
      Comparison of area under ROC curve for received models was 0.9679 vs 0.9716.
      Prognostic values of the analyzed neural model are not optimal but seem to
      surpass logistic regression model in terms of the predictive possibilities.

PMID- 16445610
TI  - Paclitaxel-platinum combination chemotherapy for advanced or recurrent ovarian
      clear cell adenocarcinoma: a multicenter trial.
AB  - The therapeutic effect of a combination of paclitaxel (PTX) and platinum (PLT) in
      ovarian clear cell adenocarcinoma (CC) patients with measurable disease has yet
      to be elucidated. In this study, we used retrospective review to evaluate the
      results of treatment with a combination of PTX and PLT in CC patients with
      measurable disease. A total of 28 patients with measurable residual CC (15 cases
      with primary disease, 13 cases with recurrent disease) treated with combination
      PTX-PLT chemotherapy was identified through medical records from ten
      institutions. Clinical response to chemotherapy was evaluated using Response
      Evaluation Criteria in Solid Tumors criteria. Of the 28 cases, 8 of 15 patients
      with primary disease (53.3%) and 3 of 13 patients with recurrent disease (23.1%)
      responded to PTX-PLT chemotherapy. The response rate for cases with late
      recurrent disease (>12 months) was 20% (1/5), whereas the rate was 25% (2/8) for
      cases with early recurrent (<12 months) or refractory disease. Our results
      indicate that the combination of PTX and PLT may have greater efficacy against CC
      than conventional PLT-based chemotherapy that does not include PTX.

PMID- 16445611
TI  - Phase I/II study of tandem cycles of high-dose chemotherapy followed by
      autologous hematopoietic stem cell support in women with advanced ovarian cancer.
AB  - The objectives of this study were to investigate the tolerability of a novel high
      dose chemotherapy (HDC) regimen with peripheral blood progenitor cell (PBPC)
      support in patients with pretreated advanced ovarian cancer and to determine the
      maximum-tolerated dose (MTD) of topotecan in this setting. Advanced ovarian
      cancer patients previously treated with platinum-based first-line therapy were
      enrolled. After PBPC mobilization and harvesting, patients received three
      consecutive cycles of HDC with PBPC support. Cycle 1 was carboplatin area under
      the concentration curve 20 and paclitaxel 250 mg/m(2). Cycle 2 was topotecan
      starting at 5 mg/m(2), dose escalated in 2 mg/m(2) increments, and etoposide 600
      mg/m(2). Cycle 3 was thiotepa 500 mg/m(2). After each cycle, PBPCs were infused.
      Granulocyte colony stimulating factor (5 microg/kg/day) was administered until
      neutrophil recovery occurred. Seventeen patients were enrolled; all were safety
      evaluable. The most common nonhematologic toxicity was grade 3 mucositis (44%).
      Engraftment of PBPCs was successful in all patients after each cycle, and no
      treatment-related deaths occurred. Of 14 patients with measurable disease, 5
      (36%) had complete responses, 2 (14%) had partial responses, and 4 (29%) had
      stable disease. The median progression-free and overall survivals were 7 and 18
      months, respectively. The MTD of topotecan was not reached. The tolerability and
      activity of this regimen in patients with advanced ovarian cancer warrant further
      investigation.

PMID- 16445612
TI  - Phase II study of the combination of pegylated liposomal doxorubicin and
      topotecan in platinum-resistant ovarian cancer.
AB  - The combination of liposomal doxorubicin and topotecan was evaluated in a phase
      II study in patients with platinum-resistant ovarian cancer. Twenty-seven
      patients received liposomal doxorubicin (30 mg/m(2)) infused at day 1, followed
      by topotecan (1 mg/m(2)) infusion daily for 5 days. Cycles were repeated every 21
      days. This combination regimen showed an overall response rate of 28%. Median
      time to progression was 30 weeks, with a median overall survival of 40 weeks.
      Grade 3/4 neutropenia was shown in 70% of patients and grade 3/4 thrombopenia in
      41% of patients. Neutropenic fever was reported in 11% of patients. After
      reviewing the first 12 patients, the internal review board decided to administer
      topotecan at a dose of 0.75 mg/m(2) and liposomal doxorubicin at 40 mg/m(2) for
      the remainder of the study. However, this adjustment did not lead to reduction in
      bone marrow toxicity nor to an improvement in dose intensity. Palmar-plantar
      erythrodysesthesia and mucositis were more reported in the second cohort but
      usually mild. The combination of liposomal doxorubicin and topotecan demonstrates
      favorable response data in platinum-resistant ovarian cancer. However,
      substantial bone marrow toxicity limits further clinical use.

PMID- 16445613
TI  - A multicenter phase II study of the cryptophycin analog LY355703 in patients with
      platinum-resistant ovarian cancer.
AB  - LY355703 is a synthetic product structurally related to the cryptophycin family
      isolated from the blue-green algae, which exerts a potent destabilization of
      microtubules during mitosis. This study was performed to determine the activity
      of LY355703 in patients with platinum-resistant advanced ovarian cancer and to
      characterize its toxicity profile. Twenty-six patients were enrolled in this
      study. Resistant disease was defined as a platinum-free interval of <6 months
      from primary treatment or rechallenge. LY355703 (1.5 mg/m(2)) was administered
      intravenously on days 1 and 8, every 3 weeks, infused over 2 h. From 24 patients
      evaluable for response, three partial responses (12.5%) and seven disease
      stabilizations were registered (29.2%), for an overall clinical benefit of 41.7%.
      Fourteen patients (58.3%) experienced a progression of the disease during
      treatment. Among the 25 patients evaluable for toxicity, two episodes of grade 3
      anemia (8%); one, grade 3 thrombocytopenia (4%); one, grade 4 elevation of
      creatinine (4%); and one, grade 3 hyperbilirubinemia (4%) were reported. LY355703
      has a modest activity in patients with platinum-resistant advanced ovarian
      cancer. Nevertheless, the considerable rate of disease stabilization in the
      absence of serious adverse events in this poor-prognosis study population
      suggests that this novel cryptophycin may deserve further investigation in this
      setting.

PMID- 16445614
TI  - Efficacy and tolerability of the ifosfamide-epirubicin combination in relapsed
      ovarian cancer.
AB  - A retrospective study evaluating the efficacy and tolerability of epirubicin
      ifosfamide (EI) in patients with relapsed advanced ovarian cancer (ROC) after
      prior chemotherapy was conducted. A total of 93 patients received epirubicin (50
      mg/m(2), day 1), ifosfamide (1500 or 2500 mg/m(2), days 1-3), and mesna monthly.
      Thirty-five percent had received one line of chemotherapy (platinum 100%, taxanes
      8%); 38%, two lines; and 27%, more than two lines. Fifty-three percent received
      2500 mg/m(2)/day ifosfamide and 47% received 1500 mg/m(2)/day ifosfamide.
      Ifosfamide was administered by continuous infusion in 12 patients. Mean number of
      courses was 4 (1-12). Grade 4 toxicity was 69% neutropenia and 12%
      thrombocytopenia. Three patients on high-dose ifosfamide as a short infusion had
      central nervous system dysfunction resulting in death. There were 84 assessable
      patients: 7 (8%), complete responses; 13 (15%), partial responses; and 20 (24%),
      stable disease. Median time to progression was 5 months (3 days to 36 months).
      The EI combination appears to be effective in ROC. However, toxicity with high
      dose ifosfamide administered by short infusion is not acceptable. Tolerability
      can be improved using ifosfamide at 1500 mg/m(2) by continuous infusion. The
      combination of ifosfamide with newer anthracycline agents such as liposomal
      doxorubicin may be an alternative and needs further evaluation for use after
      first-line taxane-based chemotherapy.

PMID- 16445615
TI  - Correlation of serum and ascitic IL-12 levels with second-look laparotomy results
      and disease progression in advanced epithelial ovarian cancer patients.
AB  - Forty-two consecutive patients with advanced epithelial ovarian cancer who
      underwent primary surgical treatment were evaluated. The control group comprised
      21 patients who had undergone surgery associated with benign pathologies. Forty
      one patients had stage III disease except one who had stage IV. Optimal debulking
      (<1 cm) was performed in all the patients who subsequently received chemotherapy.
      Based on the results of the second-look laparotomy and follow-up, the patients
      were divided into three groups: the first group had negative second-look
      laparotomy or no evidence of disease during follow-up (n= 21), the second group
      had positive second-look laparotomy or progressive disease (n= 21), and the third
      was the control group (n= 21). Interleukin-12 (IL-12) levels were measured in
      preoperative serum and intraoperative ascites samples for all the patients. The
      mean serum IL-12 levels (+/-SD) in serum (S) and ascites (A) were as follows: in
      the first group, S: 108.44 +/- 76.40 pg/mL and A: 330.93 +/- 125.25 pg/mL; in the
      second group, S: 51.80 +/- 40.95 pg/mL and A: 206.89 +/- 113.47 pg/mL; and in the
      control group, S: 36.55 +/- 33.16 pg/mL and A: 93.62 +/- 73.07 pg/mL (P= 0.01).
      In the patients with advanced ovarian cancer, IL-12 levels in serum and ascites
      were higher compared to the levels of the controls. Also, there was an inverse
      relationship between initial serum and ascitic IL-12 levels and disease
      progression.

PMID- 16445616
TI  - Impact of initial surgical access on staging and survival of patients with stage
      I ovarian cancer.
AB  - The aim of this study was to compare staging by laparoscopy and laparotomy, and
      to compare survival in patients with laparoscopy versus laparotomy as the first
      surgical access. We conducted a retrospective analysis of patients with stage I
      ovarian cancer treated surgically between 1985 and 2001, and we included those
      patients with stage I epithelial cancer for whom follow-up data were available.
      For each patient, we recorded whether initial surgical staging was by laparoscopy
      or by laparotomy, the procedures done at initial staging surgery, and the
      outcomes. The data were evaluated by analysis of variance, Chi-square test or
      Fisher's exact test, logistic regression, Cox model, and log-rank test, using
      SPSS 7.5 and STATA. Initial staging was by laparoscopy in 34 patients, laparotomy
      in 114 patients, and laparoscopy converted to laparotomy in 30 patients. In the
      laparotomy group, patient age was significantly greater and tumor size
      significantly larger, as compared to the laparoscopy group. Staging after first
      surgery was often inadequate; most notably para-aortic lymph node dissection was
      done in 0% of laparoscopy patients, 18% of laparotomy patients, and 33% of
      conversion patients. Restaging surgery has been indicated in 88% of laparoscopy
      patients, 48% of laparotomy patients, and 46% of conversion ones. After a mean
      follow-up of 40 months, survival rates were not significantly different among the
      three patient groups. No deleterious influence of laparoscopy as first surgical
      access was detected by univariate or multivariate analysis. Despite of inaccurate
      radicality and staging during initial laparoscopy, this study found no harmful
      influence of laparoscopy as first initial access on outcomes of patients with
      stage I ovarian cancer.

PMID- 16445617
TI  - A pilot study of three-cycle consolidation chemotherapy with paclitaxel and
      platinum in epithelial ovarian cancer patients with clinical complete response
      after paclitaxel and platinum chemotherapy.
AB  - The aim of this study is to evaluate the efficacy of three additional cycles of
      paclitaxel and platinum chemotherapy in epithelial ovarian cancer patients with
      clinical complete response (CR). Patients with histologically confirmed
      epithelial ovarian cancer stages II-IV with clinical CR after primary surgery and
      six cycles of chemotherapy with paclitaxel/platinum entered into the study. Three
      cycles of paclitaxel/platinum (cisplatin, carboplatin) were administered as a
      consolidation chemotherapy only in patients who agreed to the informed consent.
      Patients without further treatment served as controls. A total of 81 patients
      entered into the study. According to the informed consent, 42 patients were
      treated by the consolidation chemotherapy, and 39 patients were followed up
      without further treatment. The median actuarial disease-free survival for the
      patients with and without consolidation chemotherapy was 25.0 months and 26.0
      months, respectively (P= 0.80). The median overall survival is not reached. World
      Health Organization grade 3-4 toxicities in the consolidation arm were increased
      but showed no significant differences statistically. Although the sample size is
      small and not randomized, these results suggest that three cycles of
      consolidation chemotherapy with paclitaxel/platinum might not provide a favorable
      outcome in patients with a clinical CR.

PMID- 16445618
TI  - Malignant mixed mullerian tumors of the ovary: experience with cytoreductive
      surgery and platinum-based combination chemotherapy.
AB  - This study reviews the clinical outcome and prognosis of patients with malignant
      mixed mullerian tumors (MMMTs) of the ovary treated with optimal cytoreductive
      surgery, leaving no residual disease, and platinum-based chemotherapy. Ten
      patients diagnosed with MMMT of the ovary after complete surgical staging from
      February 1993 to February 2004 at Asan Medical Center in Korea were studied
      retrospectively. All ten patients were treated with optimal cytoreductive
      surgery, leaving no gross residual disease. Seven patients received
      ifosfamide/cisplatin chemotherapy, and the remaining three patients received
      other platinum-based combination chemotherapy. Demographic data, pathologic
      findings, treatments, and survival time were reviewed. Of the ten patients, two
      were scored at FIGO stage IIC, seven were at stage IIIC, and one was at stage IV.
      The median survival time of all ten patients was 46 months. The overall survival
      rate was 60.0% at 1 year, 40.0% at 2 years, and 20.0% at 5 years. Platinum-based
      combination chemotherapy after optimal cytoreductive surgery may be effective in
      the treatment of ovarian MMMT.

PMID- 16445619
TI  - Primary malignant mesodermal ovarian sarcomas.
AB  - Primary malignant mesodermal ovarian sarcomas are rare tumors and have a poor
      prognosis. The disease is usually diagnosed at a late stage and 5-year survivals
      are uncommon. Most patients are treated with debulking surgery followed by
      adjuvant chemotherapy. We report ten patients treated at a single institution.
      All patients underwent surgery and 90% received adjuvant chemotherapy. The median
      survival was 20 months, and only one patient survived beyond 5 years. Newer
      treatment strategies are urgently needed in the management of this disease.

PMID- 16445620
TI  - Growth regulation and transcriptional activities of estrogen and progesterone in
      human endometrial cancer cells.
AB  - Estrogen-stimulated growth of the malignant human endometrium can be balanced by
      the differentiating properties of progesterone. To study the molecular basis
      behind this, gene expression profiling was performed using complementary DNA
      microarray analysis. In this study, the human endometrial cancer cell lines ECC-1
      and PRAB-36 were used as models. The ECC-1 cell line, which expresses high levels
      of estrogen receptor alpha and is stimulated in growth by estrogens, was used to
      study estrogen regulation of gene expression. The Ishikawa sub-cell line PRAB-36,
      expressing both PRA and PRB, progesterone receptor isoforms, and inhibited in
      growth by progestagens, was used to study progesterone regulation of gene
      expression. Using these two well-differentiated human endometrial cancer cell
      lines, 148 estrogen- and 148 progesterone-regulated genes were identified. After
      functional classification, the estrogen- and progesterone-regulated genes could
      be categorized in different biologically relevant groups. Within the group of
      "cell growth and/or maintenance," 81 genes were clustered, from which a number of
      genes could be involved in arranging the cross talk that exists between estrogen
      and progesterone signaling. On the basis of analysis of the current findings, it
      is hypothesized that cross talk between estrogen and progestagen signaling does
      not occur by counterregulation of single genes, but rather at the level of
      differential regulation of different genes within the same functional families.

PMID- 16445621
TI  - Hormonal function after ovarian transposition to the abdominal subcutaneous fat
      tissue.
AB  - We previously reported a new technique for ovarian transposition to the abdominal
      subcutaneous fat tissue (OTAFT) following hysterectomy. The purpose of this study
      is to assess the hormonal function after OTAFT. From 1993 to 2000, OTAFT was
      performed in 27 patients (group A). Forty-two women underwent hysterectomy and
      retained ovaries without transposition (group B). In 19 cases, bilateral
      oophorectomy with hysterectomy was performed, and they received a hormone
      replacement therapy (HRT) (group C). Serum follicle-stimulating hormone (FSH)
      level of patients was monitored every 2-12 months, and the time of menopause
      (defined as FSH >40 mIU/mL two times consecutively) was determined in groups A
      and B. After a median follow-up of 65 months, cumulative ovarian survival did not
      show significant difference between group A and group B (HR = 0.52, 95% CI = 0.17
      1.16; P= 0.10). In patients who were 40 years old or younger, ovarian function
      declined significantly in group A compared to group B (HR = 0.29, 95% CI = 0.02
      0.91; P= 0.04). However, FSH level of postmenopausal patients in group A was not
      different from FSH level of patients in group C, but FSH level of postmenopausal
      patients in group B was significantly higher than FSH level of patients in group
      C (P= 0.002). Although the procedure of OTAFT may somewhat affect the ovarian
      function, the transposed ovary in postmenopausal women presumably still secrete a
      small amount of estrogen which is equivalent to an estrogen level by HRT.

PMID- 16445622
TI  - An analysis of surgical versus chemotherapeutic intervention for the management
      of intestinal obstruction in advanced ovarian cancer.
AB  - The objective of this study was to compare the treatment outcomes of surgical
      versus chemotherapeutic interventions for the management of intestinal
      obstruction secondary to metastatic epithelial ovarian cancer. A retrospective
      analysis of 39 patients with epithelial ovarian cancer who had 98 events of
      intestinal obstruction was performed. A medical records review of patients
      treated for advanced ovarian cancer from 1973 to 2003 was conducted. Time from
      treatment to obstruction, complications, and predictors of outcome were analyzed.
      Mean time from diagnosis of cancer to first obstruction was 38 months (range, 7
      234 months). Of 39 patients with obstruction, 5% were stage I, 2% stage II, 85%
      stage III, and 8% stage IV. Prior to first obstruction, the median number of
      prior surgeries was 2 and chemotherapy regimens 3. Sites of the 98 events of
      obstruction were small intestine, 79 (81%); large intestine, 8 (8%); and combined
      small and large intestines, 11 (11%). The mean time to re-obstruction was 6.4
      months (0-24) for chemotherapy, 5.1 months (0-40) for surgery, and 1.9 months (0
      15) for supportive care. The mean hospital stays were 7 days (2-10) for
      chemotherapy, 18 days (3-50) for surgery, and 7 days (0-20) for supportive care.
      There were 4 major complications in the chemotherapy patients, 11 in the surgical
      patients, and 2 in the supportive only patients. The only significant factor
      predictive of > or =6 month obstruction-free period was prior response to
      platinum-based chemotherapy. Of the 13 patients with a response to
      chemotherapeutic or surgical treatment, 46% had an initial response to platinum
      based chemotherapy, while 27% of 22 patients who re-obstructed in <6 months were
      platinum sensitive. In this retrospective analysis of selected patients, surgery
      and chemotherapy were found to have similar outcomes. The surgical approach had
      higher morbidity. The best predictor of either treatment's effectiveness is tumor
      sensitivity to platinum-based chemotherapeutic agents (P= 0.168).

PMID- 16445623
TI  - Ethnicity is a factor to be considered before dose planning in ovarian cancer
      patients to be treated with topotecan.
AB  - The objective of this study was to determine the efficacy and toxicity of
      topotecan in Chinese patients with ovarian cancer. A retrospective analysis on
      recurrent ovarian cancer patients receiving topotecan 1.25 mg/m(2) daily for 5
      consecutive days on a 21-day cycle from 1997 to 2002 was conducted. The patients
      included were all treated with at least two cycles of topotecan. The patient
      characteristics were compared in relation to their toxicity profile and their
      response to treatment. Response was evaluated by physical findings, imaging
      techniques, and serum CA125 level. A total of 60 patients were included in the
      study. All patients were evaluable for response and toxicities. A total of 361
      cycles were given (median, 5 per patient; range 2-15). The major toxicity was
      neutropenia, which was grade 4 in 45.0% of the patients and 10.2% of the cycles.
      Age was the only covariate predicting the occurrence of grade 4 neutropenia
      (logistic regression P= 0.046, CI 1.01-1.12). Neutropenic fever occurred in 8.3%
      of the patients. Eighteen (30%) patients were required to delay their
      chemotherapy and 11 (18.3%) required dose reduction. Nonhematologic toxicities
      were mild. The overall response rate was 21.6%, with eight (13.3%) complete
      responses and five (8.3%) partial responses. The median duration of response and
      median time to progression were 11 and 5 months, respectively. The median
      survival was 14 months. Topotecan 1.25 mg/m(2) in a five-times-daily schedule was
      well tolerated in a cohort of Chinese patients. Myelotoxicity was the most
      important side effect in our study, but the incidence is much lower than that
      reported in other studies. Age was an independent factor predicting the
      occurrence of grade 4 neutropenia.

PMID- 16445624
TI  - Malignant transformation of ovarian mature cystic teratoma.
AB  - There have been few studies concerning the clinical pathology of malignant
      transformation arising in ovarian mature cystic teratoma (MCT). Thus, the
      objective of this study is to determine clinicopathologic factors affecting
      survival in this rare tumor. From November 1992 to December 2002, 11 patients
      with malignant transformation arising in ovarian MCT were treated at Department
      of Obstetrics and Gynecology in Chonnam National University Hospital. Demographic
      characteristics, symptoms, signs, stage, mode of therapy, and results of follow
      up were reviewed retrospectively. There were 11 cases of the malignant
      transformation of ovarian MCT out of 637 cases of MCT (1.7%). The average age was
      50.6 years. Histologically, 7 out of the 11 cases were squamous cell carcinoma
      (63.7%). There were no specific clinical symptoms, but palpable abdominal mass
      was the most frequent complaint (five cases, 45.4%). As for the stage of disease,
      eight cases were in stage IA (72.7%), and the other three cases were in stage IC,
      IIB, and IIC, respectively. All the patients had surgery, and seven of them had
      adjuvant chemotherapy and two had adjuvant chemoradiation. All the patients in
      stage I survived until the period of follow-up, and their average survival time
      was 31.8 months. One patient in stage IIC died of intestinal obstruction within 9
      months from the surgery. The mechanism of the malignant transformation arising in
      ovarian MCT is not clear, but considering the fact that 80% of MCTs are diagnosed
      during the reproductive age, malignant transformation seems to be related to the
      long-term presence of nonremoved MCT in the abdomen. Accordingly, it is
      considered helpful for preventing and early detection of the malignant
      transformation to have regular ovary examination through pelvic ultrasonogram
      during the reproductive age.

PMID- 16445625
TI  - Tissue microarray analysis of EGFR and erbB2 copy number changes in ovarian
      tumors.
AB  - The objective of this study was to assess the implication of copy number changes
      of epidermal growth factor receptor (EGFR) and erbB2 genes in the etiology and
      progression of ovarian tumors. In our study, we used the highly reliable method
      of fluorescent in situ hybridization, applied on tissue microarray, containing
      1006 ovarian tumors from different malignancy, histologic type and grade, and
      tumor stage, in order to analyze the correlations between gene copy number
      changes and tumor phenotype. We established copy number changes of erbB2 in
      15.30% of malignant ovarian tumors-8.16% amplifications and 7.14% gains. The
      frequency of EGFR copy number changes was 10.67%-3.65% amplifications and 7.02%
      gains. EGFR gains occurred with approximately the same frequency in malignant
      (7.02%), low malignant potential (8.33%), and benign (7.19%) ovarian tumors.
      ErbB2 amplification was associated with clear cell type of ovarian cancer (P <
      0.04). No amplification of EGFR and erbB2 genes was established in tumors with
      low malignant potency and in benign tumors. Regarding cancer phenotype, there was
      no statistically significant association between erbB2 copy number changes and
      histologic grade as well as tumor stage of ovarian cancer. EGFR gains are early
      events in ovarian tumorigenesis. Our results showed similar frequencies of EGFR
      gains in different grade tumors, while EGFR amplification increased from grades 1
      to 2 to 3.

PMID- 16445626
TI  - p63 expression in epithelial ovarian tumors.
AB  - Ovarian cancer is a highly lethal disease and its underlying biology is poorly
      understood. The p63 is a homologue gene of the tumor suppressor p53. p63 appears
      to be important for the development and differentiation of reproductive
      epithelium and interacts with p53 in human tumorigenesis. This study presents the
      immunoexpression of the p63 in benign and malignant epithelial ovarian tumors. We
      evaluated the p63 immunoexpression in 91 ovarian benign cystadenomas (29 mucinous
      and 62 serous) and in 29 ovarian malignant tumors (3 mucinous borderline, 3
      serous borderline, 17 serous carcinomas, 2 endometrioid, 2 undifferentiated, 1
      mucinous, and 1 clear-cell carcinoma) using a monoclonal antibody clone 4A4
      (1:200), which recognizes all p63 variants. The tumors were considered p63
      positive if 5% or more cells presented nuclear immunostaining. We observed 85.7%
      of positivity in benign tumors, 50% in borderline tumors, and 8.7% in invasive
      ovarian cancer (P < .0001). The benign serous cystadenomas were positive in 91.9%
      of cases and benign mucinous cystadenomas in 72.4% (P= .02). These data suggests
      an important role of p63 in the control of ovarian epithelium behavior. The p63
      may be involved in the development of benign and malignant epithelial ovarian
      tumors.

PMID- 16445627
TI  - Procaspase-3 enhances the in vitro effect of cytosine deaminase-thymidine kinase
      disuicide gene therapy on human ovarian cancer.
AB  - Because the efficacy of genetic prodrug activation therapy (GPAT) using herpes
      simplex virus thymidine kinase (tk)/ganciclovir (GCV) or Escherichia coli
      cytosine deaminase (cd)/5-fluorocytosine (5-FC) is not satisfied in early
      clinical trials and the mechanism of both the GPATs have been shown to lead to
      the activation of cell apoptotic pathway, we hypothesized that coexpression of
      procaspase-3, a central downstream executioner of apoptotic pathways, with cd-tk
      gene leads to enhanced cell death in ovarian cancer cells in vitro. Following
      transfection with the vectors encoding cd and tk, 5-FC and GCV treatments lead to
      greater cell death in procaspase-3-expressing clones of 3AO (3AO-caspase-3) than
      control cells (3AO-pcDNA3), as well as more rapid activation of caspase-3 and
      more rapid cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP).
      There is a greater degree of cell apoptotic rate in the procaspase-3-expressing
      clones than in control cells following the treatment with cd-tk/5-FC + GCV, and
      apoptosis is the main cell death form. None of these effects is seen following
      transfection with a control vector that does not encode tk and cd (pBTdel-279).
      The results strongly suggest that coexpression of procaspase-3 may lead to a
      significant enhancement of the efficacy of cd-tk/5-FC + GCV, and this strategy
      would be a novel and promising approach for the treatment of ovarian cancer.

PMID- 16445628
TI  - Induction of G1 arrest and differentiation in MDA-MB-231 breast cancer cell by
      boehmeriasin A, a novel compound from plant.
AB  - Boehmeriasin A is a new phenanthroquinolizidine alkaloid recently isolated from
      the Boehmeria siamensis Craib (Urticaceae). In vitro biological activity assay
      demonstrated that this novel compound has wide-range, strong antitumor activity.
      This study is aimed to determine the effects of boehmeriasin A on breast cancer
      cell (MDA-MB-231 cell line). Proliferation assay and fluorescence activated cell
      sorter (FACS) showed that cell growth inhibition and G1 phase arrest of cell
      cycle were caused by boehmeriasin A. The concentrations resulting in total and
      50% growth inhibition are 0.007 and 0.0035 microg/mL, respectively. Exposed in
      0.007 microg/mL boehmeriasin A for 12 h, the G1 phase cell percent increased from
      44.8% pre-drug treatment to 66.3%. Consistent with G1 arrest and cell growth
      inhibition, cyclin E2 and cyclin D1 messenger RNA expression in the cell was down
      regulated with drug treatment. Then, few apoptotic cells were detected, and most
      other cells underwent differentiation, which is characterized by specific changes
      in cell morphology, lots of lipid droplet accumulation, and increasing expression
      of adipocyte differentiation-related protein. The result first demonstrates that
      boehmeriasin A potently inhibits the proliferation of breast cancer cell MDA-MB
      231 via the G1 phase cell cycle arrest and differentiation induction, and as
      such, may be considered as candidate chemotherapeutic and/or chemopreventive
      agent for breast cancer.

PMID- 16445629
TI  - Gonadotropins mediate DNA synthesis and protection from spontaneous cell death in
      human ovarian surface epithelium.
AB  - Gonadotropins have been implicated in the development of epithelial ovarian
      cancers. These tumors are derived from ovarian surface epithelium (OSE). The
      purpose of this study was to determine the effects of these hormones on DNA
      synthesis and spontaneous cell death in primary cultures of OSE and three
      immortalized OSE cultures. Primary cultures of OSE cells were generated from the
      ovaries of women with benign disease. The effects of follicle-stimulating hormone
      (FSH) and luteinizing hormone (LH) on DNA synthesis and cell death were
      determined using [(3)H]thymidine incorporation and JAM assays. Significant
      inductions of DNA synthesis were demonstrated with LH in 4/12 (33%) primary
      cultures of OSE and 2/3 OSE cell lines and with FSH in 4/11 (36%) primary
      cultures of OSE and 2/3 OSE cell lines. A significant protection from cell death
      was also observed in the presence of FSH in 2/4 primary cultures of OSE and 1/3
      OSE cell lines and in the presence of LH in 1/4 primary cultures of OSE and 2/3
      OSE cell lines. The results indicate that while gonadotropins have the potential
      to induce cell proliferation and protect from cell death in OSE cells in vitro,
      their effects are variable in OSE cells from different women.

PMID- 16445630
TI  - Discordant genetic changes in ovarian and endometrial endometrioid carcinomas: a
      potential pitfall in molecular diagnosis.
AB  - Endometrioid carcinoma simultaneously involving ovaries as well as the uterine
      corpus may present a diagnostic dilemma because of the difficulty in determining
      whether the lesions are separate primary tumors or metastases. It has been
      reported that the detection of clonality using microsatellite markers may be
      useful in solving this dilemma. To determine the usefulness of this technique, we
      compared the genetic alterations in microsatellite markers present in matched
      pairs of ovarian tumors from 12 patients. The study includes four ovarian cancer
      FIGO stage I and eight stage III/IV patients, and four patients also with
      independent endometrial carcinoma of the uterus. DNA from paraffin-embedded
      tissue was extracted and amplified using a multiplex polymerase chain reaction,
      after which the status of microsatellite instability and loss of heterozygosity
      in four microsatellite loci (BAT25, BAT26, D17S250, and D5S346) were determined.
      In the four patients with stage I ovarian cancer, four microsatellite markers
      were identical in one patient and three were identical in the remaining three
      patients. In high-stage patients, three markers were identical in at least 4/8
      cases. In three of four patients with uterine involvement, three of the four
      markers were identical in the uterine tumor and one of the corresponding ovarian
      tumors. These results suggest that genetic discordance does not indicate
      independent origin or metastasis of the tumor but instead a progression of
      genetic changes at separate sites probably due to the marked genetic instability
      existing in these tumors. Because of these discordant genetic changes, great
      caution should be taken when distinguishing between primary and metastatic tumors
      on the basis of microsatellite markers.

PMID- 16445631
TI  - Prophylactic salpingo-oophorectomy in 51 women with familial breast-ovarian
      cancer: importance of fallopian tube dysplasia.
AB  - We report our findings on 51 patients with a familial breast and/or ovarian
      cancer risk who underwent prophylactic bilateral salpingo-oophorectomy (pBSO).
      Patients undergoing a pBSO between January 1, 1997, and December 31, 2003, at the
      University Hospitals Leuven were reviewed retrospectively. Out of 51 patients, 37
      (72.5%) underwent genetic testing, while the 14 others (27.5%) underwent pBSO on
      the sole basis of a positive family history only. BRCA1 mutation was found in 35%
      of the tested group, while 30% were BRCA2 carriers. Mean age at intervention was
      45.3 years; 33 patients were premenopausal. In 44 patients (86%), the pBSO was
      performed laparoscopically, and in seven patients we decided laparotomy because
      of technical reasons. In four patients hysterectomy was performed.
      Histopathologically, the presence of epithelial dysplasia was observed in two
      patients (dysplasia of the fallopian tube in a BRCA2 patient; discrete focal
      atypia of tubal and ovarian epithelium in a patient with a negative BRCA1/BRCA2
      mutation analysis). Peritoneal cytology specimens (n= 28) were all negative.
      Laparoscopic pBSO is well tolerated. Concomitant hysterectomy should be
      considered, given the observed fallopian tube dysplasia and the possibility of a
      tubal remnant after pBSO.

PMID- 16445632
TI  - CA19-9 may have clinical significance in mature cystic teratomas of the ovary.
AB  - The objective of this study was to evaluate size, bilaterality, histopathologic
      origin, and the serum levels of some tumor markers in patients with mature cystic
      teratomas (MCTs) of the ovary. Retrospective study of 80 patients operated at
      Department of Obstetrics and Gynecology, Gulhane Military Medical Academy,
      Turkey, between the years 1998 and 2003 was performed. The mean age was 33.1 +/-
      11.3 years (median 34; range 15-69). The mean tumor diameter was 7.2 +/- 4.5 cm
      (median 5; range 3-20). The mean serum CA19-9 level was 101.2 +/- 179.7 IU/mL
      (range 1-841, normal value < 37), the mean serum CA125 level was 32.0 +/- 37.8
      U/mL (range 2.2-205, normal value < 35), the mean carcino-embryogenic antigen
      (CEA) level was 1.46 +/- 1.20 ng/mL (range 0.2-4.8, normal value 3.4), and the
      mean serum alpha-fetoprotein (AFP) level was 2.7 +/- 3.0 ng/mL (range 0.1-10.5,
      normal value <8.1). The elevated rate of CA19-9, CA125, CEA, and AFP was 38.8%
      (31/80), 25% (18/72), 9.1% (4/44), and 8.7% (4/46), respectively. The
      bilaterality rate was 27.5% (22/80). Patients with an elevated serum CA19-9 level
      showed significantly higher bilaterality rate (51.6% versus 12.2%, P < 0.05) than
      the patients with low levels. Likelihood ratio for bilaterality was 2.8 for CA19
      9 and 4.6 for CA125. Bilateral teratomas showed a significantly higher rate of
      ectodermal component than the unilateral ones (100% versus 74.3%, P < 0.05).
      Ovarian MCTs were diagnosed especially during the reproductive period. CA19-9 may
      be the only important marker in the diagnosis of MCTs. Elevated levels of CA19-9
      and CA125 may be an indicator of bilaterality. Since levels of CA19-9 and CA125
      may be elevated in both benign and malignant conditions, interpretation of these
      findings must be made in light of the clinical condition of the patient.

PMID- 16445633
TI  - Progression-free interval in ovarian cancer and predictive value of an ex vivo
      chemoresponse assay.
AB  - The study objective was to determine the effectiveness of a phenotypic
      chemoresponse assay in predicting response to chemotherapy measured by
      progression-free interval (PFI) in a retrospective series of ovarian cancer
      patients whose tumor specimens had been tested with the ChemoFx assay. A
      statistically significant correlation between assay prediction of response and
      PFI was observed in 256 cases with an exact or partial match between drug(s)
      assayed and received. In 135 cases with an exact match, the hazard ratio for
      progression of the resistant group was 2.9 (confidence interval [CI]: 1.4-6.3; P
      < 0.01) compared to the sensitive group and 1.7 (CI: 1.2-2.5) for the
      intermediate compared to the sensitive group. The median PFI for patients treated
      with drugs assayed as resistant was 9 months, 14 months for those with drugs
      assayed as intermediately sensitive, and PFI had not been achieved for those with
      drugs assayed as sensitive. These data indicate that the ChemoFx assay is
      predictive of PFI in ovarian cancer. As the majority of ovarian cancers display
      different degrees of response to different chemotherapy agents ex vivo, the
      incorporation of assay information into treatment selection has the potential to
      improve clinical outcomes in ovarian cancer patients.

PMID- 16445634
TI  - Analysis of gene expression patterns of ovarian cancer cell lines with different
      metastatic potentials.
AB  - The objective of this study was to investigate the key genetic changes and
      molecular mechanisms in the process of invasion and metastasis of human
      epithelial ovarian cancers. The in vitro invasion assay was used to further
      testify that the human epithelial ovarian cancer cell line SKOV3.ip1 is more
      invasive and metastatic compared with its parental line SKOV3. A total of 17,000
      human genome complementary DNA microarrays were used to compare the gene
      expression patterns of the two cell lines. Reverse transcription-polymerase chain
      reactions and Western blotting were performed to validate the results of the
      microarray. Totally, 1557 twofold differentially expressed genes were screened
      out by 17,000 human genome complementary DNA microarrays between the two cell
      lines, including some important genes such as, nm23, c-erbB-2, and other unknown
      genes or expressed sequence tags with remarkable fold changes. The results of the
      microarray experiment were further confirmed by reverse transcription-polymerase
      chain reactions and Western blotting of the nm23-H2 gene. SKOV3.ip1 is more
      invasive and metastatic than its parental line. The invasion and metastasis
      mechanism of epithelial ovarian cancer is a very complex process in which many
      important genes like nm23, c-erbB-2, as well as other unknown genes or expressed
      sequence tags were involved.

PMID- 16445636
TI  - The antiobesity drug Orlistat induces cytotoxic effects, suppresses Her-2/neu
      (erbB-2) oncogene overexpression, and synergistically interacts with trastuzumab
      (Herceptin) in chemoresistant ovarian cancer cells.

PMID- 16445635
TI  - Methylation of the insulin-like growth factor binding protein-3 gene and
      prognosis of epithelial ovarian cancer.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGFBP
      family, which regulates the mitogenic and antiapoptotic effects of insulin-like
      growth factors. Hypermethylation of the IGFBP-3 promoter has been found to
      suppress its expression. To evaluate the role of IGFBP-3 in ovarian cancer
      progression, we examined the survival of 235 consecutively selected epithelial
      ovarian cancer patients in association with IGFBP-3 promoter methylation and
      IGFBP-3 expression in tumor tissue. IGFBP-3 promoter methylation was analyzed
      using methylation-specific polymerase chain reaction. Cytosol protein was
      extracted and measured using a bicinchoninic acid assay; IGFBP-3 was measured by
      enzyme linked immunosorbent assay. Promoter methylation of the IGFBP-3 gene was
      detected in 44% (104/235) of patients. IGFBP-3 promoter methylation was
      associated with disease progression and death after adjusting for clinical and
      pathologic variables. The association was more evident in patients with early
      stage disease: RR = 2.87 (95% CI: 0.78-10.63) for disease progression and RR =
      3.94 (95% CI: 0.91-15.78) for death. Tissue levels of IGFBP-3 did not differ by
      methylation status but were inversely associated with disease stage and residual
      tumor size. These results suggest that IGFBP-3 promoter methylation may be a
      useful prognostic marker for disease progression and death in early-stage ovarian
      cancer.

PMID- 16445637
TI  - Preclinical in vivo activity of a combination gemcitabine/liposomal doxorubicin
      against cisplatin-resistant human ovarian cancer (A2780/CDDP).
AB  - Both gemcitabine and liposomal doxorubicin are antineoplastic drugs with clinical
      activity in platinum-refractory ovarian cancer. The purpose of this study was to
      evaluate the antitumor activity of a combination gemcitabine/liposomal
      doxorubicin administered to athymic mice bearing cisplatin-resistant human
      ovarian cancer (A2780/CDDP) xenografts. Emphasis was on the use of very low doses
      of each drug and of different dosing schedules. Data obtained showed that
      combined treatment with 80 mg/kg gemcitabine and 15 mg/kg liposomal doxorubicin
      produced a significant enhancement of antitumor activity compared with
      monotherapy at the same doses of these agents. Noteworthy is the fact that the
      majority of xenograft-bearing animals receiving the combination therapy
      demonstrated a complete tumor regression at the end of the study. A similar trend
      was observed when doses of both drugs were reduced to 20 mg/kg gemcitabine and to
      6 mg/kg liposomal doxorubicin. Again, three out of ten mice receiving the
      combination were tumor free at the end of the study. No significant differences
      were observed in antitumor activity when comparing the simultaneous vs the
      consecutive dosing schedule. Remarkably, no additive toxicity was observed in any
      experimental trials. These data encourage clinical trials to prove the advantages
      of this combination treatment with respect to the single-agent chemotherapy in
      platinum-refractory ovarian cancer patients.

PMID- 16445638
TI  - Irregularly shaped inclusion cysts display increased expression of Ki67, Fas, Fas
      ligand, and procaspase-3 but relatively little active caspase-3.
AB  - Human ovarian cancers are thought to arise from sequestered ovarian surface
      epithelial (OSE) cells that line the wall of inclusion cysts. Nevertheless, the
      early events toward neoplasia are not well understood. In this study,
      immunoreactivity for apoptotic proteins in human OSE of control and tumor ovarian
      sections was examined. Ki67, a marker for cell proliferation, was generally
      absent in the flat-to-cuboidal OSE cells on the ovarian surface and in regularly
      shaped inclusion cysts. Fas, Fas ligand, and caspase-3, components of the
      apoptotic pathway, were also largely absent. Ki67, Fas, Fas ligand, and
      procaspase-3 expression, though not active caspase-3 expression, was more
      frequently observed in epithelial cells lining irregularly shaped inclusion
      cysts, particularly in the columnar and Mullerian-like OSE cell types that
      resembled ovarian tumor OSE cells. Immunoreactivity for these factors as well as
      active caspase-3 was found frequently in ovarian tumors. We postulate that the
      appearance of the Fas system and its related proteins in sequestered columnar OSE
      cells of irregularly shaped inclusion cysts may contribute to balance cell growth
      with cell death, although little active caspase-3 expression was observed.
      Further studies are required to identify whether inhibition of apoptosis in
      inclusion cysts is an early event in ovarian carcinogenesis.

PMID- 16445639
TI  - Neopterin as an indicator of immune activation and prognosis in patients with
      gynecological malignancies.
AB  - Malignant tumors may contribute to host response that involves both the adaptive
      and innate immune systems. Among other biochemical indicators of systemic immune
      and inflammatory activity, activation of macrophages by interferon-gamma induces
      a marked increase in the production of neopterin. Neopterin production by
      activated macrophages is also associated with tryptophan degradation. In addition
      to tumors of other primary locations, increased urinary and serum neopterin
      concentrations have been reported in patients with gynecological cancers,
      including epithelial ovarian carcinoma, cervical carcinoma, endometrial
      carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign
      neoplasms or precancerous disorders. Increased neopterin concentrations have been
      associated with poor prognosis. Elevated levels of neopterin have also been
      observed in the tumor microenvironment. Systemic (urinary or serum) or local
      (ascitic fluid) neopterin concentrations increased after therapeutic
      administration of cytokines. Elevated neopterin concentrations have been
      associated with anemia of chronic disease and increased urinary zinc loss in
      patients with gynecological malignancy. Elevated neopterin has also been
      connected with depressed function of peripheral blood lymphocytes and a decrease
      in CD4+ T-cell numbers.

PMID- 16445640
TI  - Should punch biopsies be used when high-grade disease is suspected at initial
      colposcopic assessment? A prospective study.
AB  - The reliability and applicability of colposcopically directed cervical punch
      biopsy was assessed in a sample of 170 paired punch and large loop excision of
      cervical transformation zone (LLETZ) specimens obtained from previously untreated
      women who had been selected for treatment on the basis of cytology and/or
      colposcopic findings and in whom the entire cervical transformation zone was
      visible. A single punch biopsy was taken immediately before the LLETZ, and all
      the specimens were reviewed by a single pathologist. Nine (5.3%) punch biopsies
      were inadequate. In terms of whether or not there was cervical intraepithelial
      neoplasia (CIN), the chance-corrected kappa analysis rated overall agreement as
      poor (kappa = 0.21, 95% confidence limits 0.02-0.39), whereas in terms of
      histologic grade, it was fair to moderate (kappa = 0.32, 95% confidence limits
      0.23-0.42). Punch biopsy tended to underestimate the disease. The sensitivity and
      specificity of colposcopically directed punch biopsy for the detection of high
      grade CIN was 74% and 91%, respectively, with positive- and negative predictive
      values of 97% and 48%, respectively. Two microinvasive and two intraepithelial
      glandular lesions were missed on punch biopsy. Punch biopsy should be avoided
      when high-grade disease is suspected.

PMID- 16445641
TI  - A cytohistologic study of atypical glandular cells detected in cervical smears
      during cervical screening tests in Iran.
AB  - Atypical glandular cells (AGC) often cause diagnostic uncertainty in
      cervicovaginal smears. To determine the incidence of significant pathologies
      associated with AGC on Papanicolaou test, AGC smears were correlated with
      subsequent biopsy diagnoses. A retrospective review of archives of our cytology
      files for cervicovaginal smears diagnosed as AGC from April 1998 to March 2001
      was performed. In 9390 cervicovaginal smears, AGC were reported in 76 (0.81%)
      cases, with histologic follow-up in 42 patients (55.3%). Twenty-two patients
      (52.4%) had preneoplastic or neoplastic, squamous, or glandular lesions on
      histologic examination. Among them were cervical intraepithelial neoplasia, basal
      cell abnormality of undetermined significance, cervical adenocarcinoma,
      endometrial hyperplasia or adenocarcinoma, vaginal adenocarcinoma, endocervical
      glandular dysplasia, metastatic breast carcinoma, and simple nonvillous
      trophoblastic tissue. Therefore, presence of AGC in cervical smears may exhibit a
      spectrum of findings, ranging from benign/reactive changes to squamous or
      glandular premalignancy or malignancy. A majority of these lesions are squamous
      dysplasia, and a significant number of patients had glandular malignancy. The
      results of the current study underline the importance of follow-up for patients
      with the diagnosis of AGC. To our knowledge, this is the first report in Iran
      showing the significance of AGC diagnosis.

PMID- 16445642
TI  - Role of human papillomavirus DNA testing in management of women with atypical
      squamous cells of undetermined significance.
AB  - To find the sensitivity, specificity, and positive and negative predictive values
      of the high-risk group human papillomavirus (HPV) DNA testing as a triage tool to
      detect high-grade squamous intraepithelial lesions (HSILs, ie, cervical
      intraepithelial neoplasia [CIN] 2 or worse) in women with a cytologic smear
      showing atypical squamous cells of undetermined significance (ASC-US). All new
      cases with cytologic smears showing ASC-US that presented in King Chulalongkorn
      Memorial Hospital from January 2003 to November 2003, excluding known cases of
      HSILs and pregnancies, were enrolled. Cervical cell samplings were done by
      cervical cytobrush technique and tested for high-risk group HPV with the Hybrid
      Capture 2 (HC2) test. All participants were examined under a colposcope. Then
      cervicographs were taken before colposcopic-directed cervical biopsies were done.
      Of the 90 ASC-US cases enrolled, the pathologic results were normal in 30.0%,
      squamous metaplasia in 16.7%, CIN 1 in 37.8%, CIN 2 in 1.1%, CIN 3 in 11.1%, and
      microinvasive cervical carcinoma in 3.3%. The prevalence of HSILs and the
      prevalence of high-risk HPV detection were 15.6% and 38.9%, respectively. Using
      pathologic results from cervical biopsy as the gold standard, the HC2 has the
      sensitivity, specificity, and positive and negative predictive values of 85.7%,
      69.7%, 34.3%, and 96.4%, respectively, to detect HSILs. High-risk group HPV
      detection can be used as an additional triage test to detect HSILs in women
      having ASC-US with high sensitivity and negative predictive value.

PMID- 16445643
TI  - Human papillomavirus and cervical cancer from a prospective study in Khon Kaen,
      Northeast Thailand.
AB  - The risk of developing carcinoma of the cervix in women infected with human
      papillomavirus (HPV) was estimated in a nested case-control analysis of 33
      cancers (invasive and in situ) and 113 controls, matched by age and sex, from an
      ongoing cohort study of lifestyle and cancer in a rural population of Northeast
      Thailand. Oncogenic HPV types were present in 10.8% of control women and in 31/33
      of the carcinoma cases, corresponding to an odds ratio of 130.6 (95% CI 11.7
      1457.0). There was no significant difference in risk between prevalent cancer
      cases (diagnosed less than 3 months after HPV testing) and incident cases
      (diagnosed an average of 2.1 years later). HPV 16 and 18 were the most prevalent
      oncogenic HPV types present. The results confirm that some two of three of
      cervical cancer cases in this population of Northeast Thailand are caused by HPV
      16 and 18.

PMID- 16445644
TI  - Development of anticancer gene vaccine interact with human papillomavirus
      oncoprotein inhibition.
AB  - Adeno-associated virus (AAV) Rep 78 protein is known to inhibit the promoter site
      of several oncogenes and viral genes, including the human papillomavirus (HPV)
      type 16 E6 transforming genes. The biochemical studies of Rep 78 have been
      reported, but the effects of Rep 78 gene-mediated inhibition of HPV 16 E6
      promoter activity on the various human cervical carcinoma cells have not been
      characterized. pEGFP-N1 vector, cloned by AAV-mediated Rep 78, is transfected
      into cervical carcinoma cells. Transfection efficiency of Rep 78 was
      approximately 30-60% different. Messenger RNA (mRNA) and protein expression of
      Rep 78 gene was significantly higher on day 1 of the transfection of Rep 78 DNA
      in CaSki cells, and DNA level of HPV 16 E6 was decreased on day 1 of the
      transfection. The growth of CaSki cervical cancer cells was only 10-15% inhibited
      by Rep 78, and the other cervical cells, HeLa, HeLaS3, HT3, and QGU, were
      unaffected by Rep 78 transfection. In spite of the high efficiency of Rep 78 gene
      transformation and expression rate, we could not show the significant growth
      inhibition in various cervical cancer cell lines. Taken together, long-term
      expression of Rep 78 strategy might be needed for cervical carcinoma gene therapy
      using AAV vector.

PMID- 16445645
TI  - Phase II study of the American Brachytherapy Society guidelines for the use of
      high-dose rate brachytherapy in the treatment of cervical carcinoma: is 45-50.4
      Gy radiochemotherapy plus 31.8 Gy in six fractions high-dose rate brachytherapy
      tolerable?
AB  - In 2000, the American Brachytherapy Society (ABS) published incompletely
      evaluated guidelines for curative chemoradiation and high-dose rate (HDR)
      brachytherapy for cervical cancer: our aim was to assess guideline tolerability
      in an Asian population. From 2000, all stage I-IVA cervical carcinoma patients
      were treated following ABS guidelines. Early disease (FIGO stage I/II <4 cm)
      received 45 Gy whole-pelvis external-beam radiation (EBRT) at 1.8 Gy/fraction,
      while advanced-stage disease received 50.4 Gy: no central shielding was used. All
      patients were planned to receive chemotherapy during EBRT, cisplatin 40 mg/m(2)
      weekly. All patients received 31.8-Gy HDR brachytherapy (six fractions of 5.3
      Gy/fraction) to point A via three-channel applicators. Radiotherapy was completed
      within 8 weeks. Toxicity scoring used Common Toxicity Criteria. Nineteen of 21
      (90.4%) patients (8 early, 13 advanced stage) received planned radiation, and
      85.7% received planned chemotherapy. Median follow-up was 24 months (range 9-50
      months). Three-year overall survival (S) was 79.1% and disease-free survival
      (DFS) was 64.8%. S/DFS for early and advanced stage was 85.7%/85.7% and
      73.3%/47.1%, respectively. Complete response (CR) was achieved by 85.7% of
      patients, partial response 14.3%. For those in CR, there were no local failures.
      Acute cystitis occurred in 23.8%, proctitis 4.8%, and gastroenteritis 47.6%. Late
      cystitis occurred in 9.5%, gastroenteritis 4.8%, and genitourinary fistula (in
      the presence of progressive disease) 4.8%. No grade 3/4 treatment-related
      toxicity occurred. The ABS guidelines were well tolerated and efficacious in our
      study, although longer follow-up is required. Further studies are warranted to
      validate safety and efficacy of the recommendations.

PMID- 16445646
TI  - Unilateral groin and pelvic irradiation for unilaterally node-positive women with
      vulval carcinoma.
AB  - It is essential that any patient with resected vulval cancer and significant
      nodal disease receive optimal adjuvant treatment with radiation. Adequate
      radiotherapy for such patients with unilateral positive groin nodes has not been
      defined. Whether both groins and pelvic sidewalls should be irradiated or only
      the affected (node positive) side remains unclear. From our registry, we
      identified all patients with primary, previously untreated squamous cell
      carcinoma of the vulva undergoing bilateral inguinofemoral lymphadenectomy
      (superficial and deep nodes) and having unilaterally positive groin nodes treated
      with unilateral groin and pelvic radiotherapy (44 Gy in 22 fractions). Clinical
      and pathologic records were reviewed to identify the anatomical site and timing
      of recurrences in these patients and determine whether unilateral groin and
      pelvic irradiation was sufficient for disease control on the node-negative side.
      From 1983 to 2002, 20 patients with unilateral positive nodes treated with
      unilateral groin and pelvic irradiation were identified. Nineteen patients were
      classed as having FIGO stage III disease and one as FIGO stage IV due to
      involvement of the rectal mucosa. There were nine patients with disease
      recurrences in this group (45%). The disease-free interval ranged from 4 to 31
      months (median time to recurrence, 9 months). All nine patients had local or
      regional failures, the most common site being the ipsilateral groin (six of nine
      patients). One patient was also found to have distant metastases. There were no
      recurrences noted in the contralateral (nonirradiated) groin or pelvic sidewall.
      Recurrence was generally fatal. Eight of the nine patients subsequently died of
      their disease. The ninth patient died of another cause. There was a high
      incidence of regional failure after unilateral groin and pelvic radiotherapy, but
      there were no recurrences on the nonirradiated, node-negative side. Although a
      small series, we speculate that there is no apparent disadvantage to
      administering unilateral adjuvant radiotherapy for unilaterally positive groin
      nodes and encourage further studies in order to more confidently determine
      whether the tendency observed in our center holds true.

PMID- 16445647
TI  - Vaginal stenosis in patients treated with radiotherapy for carcinoma of the
      cervix.
AB  - The aim of our study was to determine the incidence, timing, and severity of
      vaginal stenosis in patients with carcinoma of the cervix who had received pelvic
      and/or vaginal radiotherapy as part of their treatment. We also sought to
      determine if there were any predisposing factors for the development of stenosis.
      A retrospective chart review was undertaken for all the patients diagnosed with
      carcinoma of the cervix between January 1, 1990, and December 31, 2000 and
      treated with pelvic and/or vaginal radiation at Westmead Hospital. Since January
      1, 1990, data regarding vaginal stenosis has been prospectively recorded on all
      the patients. Data collected included patient demographics, stage of disease,
      treatments administered, and incidence, timing, and severity of vaginal stenosis.
      One hundred and eighty-eight patients were treated. Mean age was 58.6 years.
      Thirteen percent of patients had stage IB disease, 45% had stage II disease,
      39.5% had stage III disease, and 1.5% had stage IV disease. One hundred and
      seventy-nine patients returned for follow-up, and data regarding vaginal toxicity
      were available in 98%. Twenty-seven percent had grade 1 toxicity (partial
      stenosis or shortening but not complete occlusion), and 11% had grade 2 (complete
      occlusion). Stenosis of any grade was noted at a mean of 9.6 months and median of
      7.5 months (range, 26 days-5.6 years) from completion of treatment. The only
      prognostic factor associated with increased risk of stenosis was age greater than
      50 years (odds ratio 2.26). Vaginal stenosis is a common complication of pelvic
      and vaginal radiotherapy, occurring in 38% of patients. Stenosis occurs most
      often in the first year after treatment. Patients over the age of 50 are most at
      risk.

PMID- 16445648
TI  - Long-standing complications after treatment for cancer of the uterine cervix-
      clinical significance of medical examination at 5 years after treatment.
AB  - The purpose of this study is to investigate the side effect in patients who
      survived for more than 5 years after initial treatment for invasive cervical
      cancer. Between January 1984 and December 1997, 341 patients underwent primary
      treatment for invasive cervical cancer. One hundred nine patients who underwent
      medical examinations at 5 years after primary treatment were reviewed. The
      patients were divided into three groups: radical surgery alone (group A),
      radiotherapy alone (group B), and radical surgery with postoperative radiotherapy
      (group C). Dysuria was seen in 8%, and positive catheterized urine culture was
      noted in about 20% of groups A and C. Hydronephrosis was seen in 2% and 9% of
      groups A and B, respectively. Colitis or ulcer detected by proctosigmoidoscopy
      was noted in 15%, 50%, and 43% of groups A, B, and C, respectively, frequently
      observed in radiotherapy group (P= 0.0029). Lymphocyst was still present in 6% of
      group A, and leg edema was noted in 14%, 6%, and 15% of groups A, B, and C,
      respectively. Long-standing abnormal findings including urinary and bowel
      complications were presented in this study. Periodic physical examination after
      treatment should be performed because complications existed over a long time.

PMID- 16445649
TI  - Tirapazamine plus cisplatin in advanced or recurrent carcinoma of the uterine
      cervix: a Southwest Oncology Group study.
AB  - The objective of this study was to determine objective response and overall
      survival (OS) and progression-free survival (PFS) following cisplatin plus
      tirapazamine treatment in eligible consenting patients with metastatic or
      recurrent squamous or adenosquamous carcinoma of the cervix. Treatment consisted
      of intravenous tirapazamine, 260 mg/m(2), followed by cisplatin, 75 mg/m(2),
      every 21 days for six cycles. Of 56 registered cases, 52 were evaluable for
      toxicity. There were six grade 4 toxicities (anemia [three], dyspnea [one],
      neutropenia/granulocytopenia [one], and dehydration [one]). Fifty-three patients
      were evaluable for response, OS, and PFS. The 6-month OS rate was 56.6% (95% CI
      43.3-69.9%). The objective response rate was 32.1% (4 complete [2 confirmed and 2
      unconfirmed] and 13 partial [8 confirmed and 5 unconfirmed]). Higher response
      rates (16/34 [47.1%] vs 1/19 [5.3%], P= 0.0018) were observed in patients who had
      not previously received radiation-sensitizing chemotherapy, as were OS and PFS
      (13.9 vs 4.0 months, P < 0.0001; 5.3 vs 1.8 months, P= 0.01). The OS was
      considered too low to warrant further testing in this disease setting. Despite
      this, tirapazamine plus cisplatin was active in patients who had not received
      cisplatin previously. Prior use of radiosensitizing chemotherapy impacted
      response and survival significantly and should be considered in future clinical
      trials.

PMID- 16445650
TI  - Oxygenated and reoxygenated tumors show better local control in radiation therapy
      for cervical cancer.
AB  - The presence of hypoxic cells is one of the major factors affecting resistance
      against radiation therapy. In the clinical setting, little information exists as
      to the relationship between intratumoral oxygen partial pressure (pO(2)) and
      outcome. This study involved 30 consecutive patients with cervical cancer, who
      were treated with a combination of external and high-dose rate intracavitary
      irradiation. The pO(2) was measured before radiation therapy and at 9 Gy, using a
      needle-type polarographic oxygen electrode. The mean intratumoral pO(2) before
      radiation therapy was 17.3 +/- 10.8 mm Hg. The 3-year local control rates of
      patients with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg before radiation therapy
      were 52% and 100%, respectively, representing a significant difference (P=
      0.035). At 9 Gy, mean intratumoral pO(2) was 23.6 +/- 9.1 mm Hg, a significant
      increase compared to the value before radiation therapy (P= 0.006). The 3-year
      local control rates of tumors with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg at 9
      Gy were 35% and 93%, respectively, representing a significant difference (P=
      0.001). The significantly better local control for oxygenated tumors at 9 Gy as
      well as before radiation therapy indicated that the oxygen effect and
      reoxygenation by radiation played an important role in local control in radiation
      therapy for cervical cancer.

PMID- 16445651
TI  - Routine computerized tomography scanning, groin ultrasound with or without fine
      needle aspiration cytology in the surgical management of primary squamous cell
      carcinoma of the vulva.
AB  - We set out to study whether computerized tomography (CT) scanning of the vulva
      and the groin and groin ultrasound scanning (USS) alone or with fine needle
      aspiration cytology (FNAC) (USS/FNAC) influenced or could influence the surgical
      management of primary squamous cell carcinoma of the vulva (SCCaV). Forty-four
      patients underwent surgery for primary SCCaV following radiologic imaging by one
      or more modalities. Patient details included the clinical assessment of the
      carcinoma, radiologic findings, the operation performed, and whether the decision
      regarding the type and extent of surgery for the vulval carcinoma and, in
      particular, for the groin node dissection was or could be influenced by the
      radiologic findings. The age range was 38-87 years, with a median of 74 years. A
      total of 75 groin dissections were performed. Twenty-five of the 44 patients
      (56.8%) did not have groin node metastasis, 14 had unilateral metastasis (31.8%),
      and 5 (11.4%) had bilateral metastasis. All cases with histologically proven
      nodal status were analyzed to compare the preoperative imaging status with the
      histology. The calculated sensitivity, specificity, negative predictive value,
      and positive predictive value for CT were 58%, 75%, 75%, and 58%, for USS alone
      87%, 69%, 94%, and 48%, and for USS-guided FNAC-80%, 100%, 93%, and 100%,
      respectively. There was no patient in whom surgical planning for the vulval
      carcinoma or the groin nodes was or could be altered by the CT findings. The data
      do not support the routine use of CT scanning in patients with primary SCCaV,
      either in assessment of the primary vulval carcinoma or in detecting groin nodal
      metastases. For the groin nodes, USS/FNAC is superior to CT in assessing disease
      status. In contrast to CT, USS/FNAC may have a useful clinical role in the
      management of the groin nodes in vulval carcinoma.

PMID- 16445652
TI  - Detection of chromosomal aberrations by fluorescence in situ hybridization in
      cervicovaginal biopsies from women exposed to diethylstilbestrol in utero.
AB  - Epidemiologic studies have associated estrogens with human neoplasms such as
      those in the endometrium, cervix, vagina, breast, and liver. Perinatal exposure
      to natural (17beta-estradiol [17beta-E(2)]) and synthetic (diethylstilbestrol
      [DES]) estrogens induces neoplastic changes in humans and rodents. Previous
      studies demonstrated that neonatal 17beta-E(2) treatment of mice results in
      increased nuclear DNA content of cervicovaginal epithelium that precedes
      histologically evident neoplasia. In order to determine whether this effect was
      associated with chromosomal changes in humans, the frequencies of trisomy of
      chromosomes 1, 7, 11, and 17 were evaluated by the fluorescence in situ
      hybridization (FISH) technique in cervicovaginal tissue from 19 DES-exposed and
      19 control women. The trisomic frequencies were significantly elevated in 4 of
      the 19 (21%) DES-exposed patients. One patient presented with trisomy of
      chromosomes 1, 7, and 11, while trisomy of chromosome 7 was observed in one
      patient. There were two patients with trisomy of chromosome 1. Trisomy of
      chromosomes 1, 7, 11, and 17 was not observed in the cervicovaginal tissue taken
      from control patients. These data suggest that DES-induced chromosomal trisomy
      may be an early event in the development of cervicovaginal neoplasia in humans.

PMID- 16445653
TI  - HER-2 codon 655 polymorphism in cervical carcinogenesis.
AB  - HER-2 codon 655 polymorphism together with human papillomavirus (HPV) types were
      examined in a total of 279 cervical smear samples. Forty-nine patients with high
      grade squamous intraepithelial lesion had higher frequency of high-risk HPV than
      167 patients with low-grade squamous intraepithelial lesion and 63 controls.
      There was no statistical difference in the frequencies of HER-2 Ile/Ile, Ile/Val,
      and Val/Val genotypes between squamous intraepithelial lesions (SILs) and
      controls. When the Ile/Ile genotype was compared to the Ile/Val + Val/Val
      genotypes, there was also no statistical difference in the genotype prevalence
      between SILs and controls either in 91 or 188 patients with or without high-risk
      HPV, respectively. These results suggest that the HER-2 polymorphism at codon 655
      in cervical cell samples is unlikely to be associated with HPV status and the
      onset of cervical cancer in a Japanese population.

PMID- 16445654
TI  - HOXB homeobox gene expression in cervical carcinoma.
AB  - The homeobox (HOX) genes are a family of transcription factors that bind to
      specific DNA sequences in target genes regulating gene expression. Thirty-nine
      HOX genes have been mapped in four conserved clusters: A, B, C, and D; they act
      as master genes regulating the identity of body segments along the
      anteroposterior axis of the embryo. The role played by HOX genes in adult cell
      differentiation is unclear to date, but growing evidence suggests that they may
      play an important role in the development of cancer. To study the role played by
      HOX genes in cervical cancer, in the present work, we analyzed the expression of
      HOXB genes and the localization of their transcripts in human cervical tissues.
      Reverse transcription-polymerase chain reaction analysis and nonradioactive RNA
      in situ hybridization were used to detect HOXB expression in 11 normal cervical
      tissues and 17 cervical carcinomas. It was determined that HOXB1, B3, B5, B6, B7,
      B8, and B9 genes are expressed in normal adult cervical epithelium and squamous
      cervical carcinomas. Interestingly, HOXB2, HOXB4, and HOXB13 gene expression was
      found only in tumor tissues. Our findings suggest that the new expression of
      HOXB2, HOXB4, and B13 genes is involved in cervical cancer.

PMID- 16445655
TI  - Evidence of human papillomavirus infection, enhanced phosphorylation of
      retinoblastoma protein, and decreased apoptosis in sarcomatoid squamous cell
      carcinoma of uterine cervix.
AB  - Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix, characterized
      by biphasic components of sarcomatoid and squamous neoplastic cells, is a rare
      entity with uncertain pathogenesis. To date, less than 20 cases have been
      mentioned. Although the rarity of this diagnosis makes it difficult to draw firm
      conclusions from limited data, it does seem that SSCC is an aggressive tumor. In
      this study, we present a 31-year-old patient with abnormal vaginal bleeding. The
      diagnosis of SSCC was confirmed through pathologic examinations from hysterectomy
      specimen. Its epithelial origin was demonstrated by immunohistochemical studies.
      The expression of p53, HER2/neu, and c-kit was not enhanced in this tumor.
      Importantly, it was human papillomavirus type 16, positive by polymerase chain
      reaction and in situ hybridization studies. Enhanced immunostaining for phospho
      retinoblastoma protein and decreased apoptosis compared with the squamous cell
      carcinoma counterpart were observed. This report characterizes the first
      description of molecular features in SSCC that may account for its aggressive
      behavior.

PMID- 16445656
TI  - Suppression of telomerase activity and arrest at G1 phase in human cervical
      cancer HeLa cells by all-trans retinoic acid.
AB  - Of all neoplasms found in women, cervical cancer has the third highest incidence
      and causes the fourth most deaths. All-trans retinoic acid (ATRA) may be with
      chemopreventive potential on cervical cancer, but the mechanisms underlying is
      not clear. To investigate the mechanisms, human cervical cancer HeLa cells were
      treated with ATRA for 1, 2, 3, or 4 days in vitro. We found that ATRA inhibited
      the growth of HeLa cells in a dose-dependent manner at the concentrations from
      0.3 to 9.6 mumol/L. Flow cytometric analysis showed that HeLa cells were arrested
      at G0/G1 phase by ATRA, and the aneuploidy was found when cells were treated for
      4 days, which is the first report that ATRA causes aneuploid cycle in HeLa cells.
      The expression of human telomerase catalytic subunit messenger RNA was decreased
      remarkably by ATRA. These findings suggested that the inhibition of telomerase
      activity and arrest of cells at G0/G1 phase might be the key steps through which
      ATRA inhibits the proliferation of HeLa cells. Our results provide a possible
      mechanistic explanation for the growth inhibitory effect of ATRA on HeLa cells.
      Therefore, retinoids may have therapeutic potential to complement current
      treatments of cervical cancers.

PMID- 16445657
TI  - Overexpression of p16 INK4a as an indicator for human papillomavirus oncogenic
      activity in cervical squamous neoplasia.
AB  - Overexpression of p16(INK4a) has been observed when retinoblastoma protein is
      inactivated by high-risk human papillomavirus (HPV) oncoprotein E7. We
      investigated overexpression of p16(INK4a) and HPV infection in cervical squamous
      neoplasia to evaluate the oncogenic potential among various HPV subtypes. The
      high-risk HPV was detected by PCR in 69.8% (37/53), 97.5% (39/40), 91.7% (44/48),
      and 100% (16/16) of cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, and
      squamous cell carcinoma (SCC), respectively. The p16(INK4a) overexpression was
      investigated immunohistochemically using a p16(INK4a)-specific monoclonal
      antibody (clone E6H4). In high-risk HPV positive cases, 32.4% (12/37) of CIN1,
      82.1% (32/39) of CIN2, 93.2% (41/44) of CIN3, and all (16/16) SCC showed
      p16(INK4a) overexpression. The incidence of p16(INK4a) overexpression was
      significantly different between CIN1 and CIN2, suggesting that the disorder of
      cell cycle regulation by HPV frequently occurred from CIN2. As for CIN1 cases,
      p16(INK4a) overexpression was observed more frequently in HPV16 and HPV52 than in
      HPV51 and HPV35. Using p16(INK4a) as a bio marker of HPV oncogenic activity, we
      demonstrate that the level of pRb dysfunction by high-risk HPV varied from
      subtypes and was getting more frequent from CIN2.

PMID- 16445658
TI  - Pelvic floor dysfunction and radical hysterectomy.
AB  - Although the survival outcome for treated, early-stage, node-negative cervical
      cancer is excellent, the operation of radical hysterectomy conveys major
      morbidity, particularly with respect to bladder and bowel function. There may be
      some degree of spontaneous recovery, but a significant proportion of
      postoperative women will have to live with the disabling effects of surgery for
      decades, and few seek help for their distress. As such, quality of life issues
      have become highly relevant in the management of this disease, and attention has
      turned to reducing morbidity, especially to the pelvic viscera. This review
      presents an overview of the surgical mechanisms presumed to be responsible for
      pelvic floor denervation and describes subsequent bladder and bowel dysfunction,
      together with future possibilities for minimizing morbidity, including less
      radical, more individual surgery, and nerve-sparing techniques.

PMID- 16445659
TI  - Pelvic exenteration without external urinary or fecal diversion in gynecological
      cancer patients.
AB  - In 1993, the authors introduced an orthotopic bladder replacement technique in
      the treatment of gynecological cancer patients. In this series, they report their
      long-term experience with orthotopic urinary reconstruction in case of primary-
      and radiotherapy-treated recurrent gynecological malignancies. Between 1993 and
      2003, in 29 patients orthotopic ileocecal ascending colon reservoirs (Budapest
      pouch) were created. Twenty-one of the 29 patients received radiotherapy prior to
      their operation. In 12 out of these 29 cases, the fecal stream was reconstructed
      with the use of low rectal anastomosis. Two patients (6.9%) died in the
      perioperative period. Orthotopic reconstruction of the lower urinary system was
      successful in 77% of the cases. Success rate was 68% in the irradiated cohort of
      patients. All orthotopic bladder replacement patients voided voluntarily at the
      time of their follow-up, without the need of self-catheterization, and 23.5% of
      them complained of some degree of daytime incontinence and 47% of nighttime
      incontinence. Low rectal anastomosis reconstruction of the fecal stream was
      successful in all but one case. Our present experience demonstrated that anterior
      and total supralevator pelvic exenteration in patients with gynecological
      malignancies is feasible with orthotopic reconstruction of the lower urinary
      tract.

PMID- 16445660
TI  - Urodynamic study on postsurgical bladder function in cervical cancer treated with
      systematic nerve-sparing radical hysterectomy.
AB  - The objective of this study was to assess the postsurgical bladder function by
      urodynamic study in patients with cervical cancer treated with nerve-sparing
      radical hysterectomy. A total of 27 consecutive patients were included in the
      study. Of the 27 patients, autonomic nerves had been completely preserved at
      least on one side in 22 patients (group A), and autonomic nerves could not be
      successfully preserved in five patients (group B). In group A, there was no
      significant difference in compliance at the moment of strong desire to void,
      maximum flow rate, and residual urine volume between before the operation and at
      12 months after the operation. However, abdominal pressure at maximum flow had
      significantly increased in patients of group B than of group A. Detrusor
      contraction pressure at maximum flow had significantly decreased in patients of
      group B than of group A. Bladder sensation was diminished in three cases (60%) of
      group B but preserved in all the patients of group A. Although it is still
      preliminary, our surgical technique described in this report is thought to be
      effective for preservation of bladder function. For further evaluation of the
      efficacy of nerve-sparing radical hysterectomy in terms of quality of life and
      survival of patients, a prospective randomized trial needs to be performed.

PMID- 16445661
TI  - How can we predict ureteral obstruction after gynecological surgery? The changes
      in Doppler resistive index and plasma creatinine and magnesium concentrations
      after surgical, unilateral ureteral obstruction in a rabbit model.
AB  - The aim of this study is to evaluate the changes in Doppler resistive index (RI)
      and plasma creatinine and magnesium concentrations after unilateral ureteral
      obstruction in a rabbit model. Fourteen adult female rabbits were used in this
      study. In seven rabbits, the left ureter was ligated with silk suture, and the
      control group was sham operated. Before surgery and on the second and seventh
      days after surgery, blood samples were obtained to measure plasma creatinine and
      magnesium concentrations. Doppler RIs of both kidneys were also measured before
      surgery and on the second and seventh days after the surgical procedure. With
      regard to magnesium levels, there was a significant within-subjects sessions
      difference [F(2, 20) = 15.21, P= 0.001] indicating a decrease through sessions.
      Magnesium concentrations decreased significantly at the postoperative second and
      seventh days compared to preoperative baseline levels (P= 0.003 and P= 0.001,
      respectively). Multifactorial analysis of variance was applied for each session
      separately with laterality, and groups as factors. The Doppler RI and the
      creatinine level did not show any significant differences or interactions for all
      sessions (P > 0.05). The decreasing plasma magnesium concentration after surgery
      may indicate ureteral injury; however, Doppler studies and creatinine levels may
      not be useful as well.

PMID- 16445662
TI  - Routine follow-up after treatment for a gynecological cancer: a survey of
      practice.
AB  - The objective of this study was to determine current practice with regards to
      follow-up after gynecological malignancy. A questionnaire survey of all lead
      clinicians in gynecological cancer centers in England was done. The most common
      duration of routine follow-up was 5 years for all of the main gynecological
      cancers (ovarian, endometrial, vulval, and cervical). The most common follow-up
      patterns were three monthly for 2 years then six monthly for 3 years after
      ovarian cancer; three monthly for the first year, four monthly for the second
      year, six monthly for the third year then annually for 1 year after endometrial
      cancer; three monthly for the first year, four monthly for the second year, six
      monthly for the third and fourth years, then annually for 1 year after vulval
      cancer; three monthly for the first year, four monthly for the second year, six
      monthly for the third and fourth years, then annually for 1 year after cervical
      cancer. The test for CA125 was routinely performed by 67% of cancer networks to
      detect recurrence after ovarian cancer. Routine follow-up after gynecological
      cancer continues to be standard practice, despite limited evidence to support its
      use. Prospective research is needed to determine best practice.

PMID- 16445663
TI  - Preoperative and intraoperative assessment of myometrial invasion and histologic
      grade in endometrial cancer: role of magnetic resonance imaging and frozen
      section.
AB  - The objective of this study was to determine the value of myometrial invasion by
      magnetic resonance imaging (MRI), histologic typing and grading by endometrial
      biopsy, and the intraoperative evaluation of both parameters by frozen section in
      the evaluation of endometrial cancer. The preoperative and intraoperative records
      of 180 patients with endometrial cancer were used to compare the preoperative
      endometrial biopsy, the myometrial invasion by MRI, and the intraoperative frozen
      sections, with the final histopathologic findings. The preoperative endometrial
      biopsy gave us the tumor histologic type and grade. MRI gave us the depth of
      myometrial invasion. The evaluation of intraoperative frozen sections gave us the
      tumor histologic type, the tumor grade, and also the myometrial invasion.
      Patients were classified as low risk (grade 1 and 2, and myometrial invasion
      <50%) and high risk (grade 3 or myometrial invasion >50%). Standard statistical
      calculations were used. Evaluation of the tumor grade by preoperative biopsy has
      a sensitivity and a specificity of 75% and 95%, respectively. Evaluation of the
      tumor grade by intraoperative biopsy has a sensitivity and a specificity of 40%
      and 98%, respectively. Evaluation of the depth of myometrial invasion with MRI
      has a sensitivity and a specificity of 79% and 82%, respectively. Evaluation of
      the depth of myometrial invasion with intraoperative frozen sections has a
      sensitivity and a specificity of 74% and 95%, respectively. Evaluation of all
      four of the parameters together has a sensitivity and a specificity of 80% and
      82%, respectively with a kappa of 0.621. In our opinion, the combination of
      preoperative biopsy and intraoperative frozen section is the best way to decide
      whether a lymphadenectomy is necessary with a low rate of understaging patients.
      MRI would have a fringe benefit in these patients.

PMID- 16445664
TI  - Clear cell adenocarcinoma of the endometrium is a biologically distinct entity
      from endometrioid adenocarcinoma.
AB  - Clear cell adenocarcinoma (CCA) of the endometrium has a poor prognosis, although
      the biologic features of this rare tumor are not clear. In this study, we
      analyzed the expression of biologic markers relating to carcinogenesis, tumor
      growth, and progression. Thirteen cases of CCA were compared with cases of
      endometrioid adenocarcinoma (EMA) of the endometrium. Immunohistochemical
      staining for p53; Ki-67; cyclins A, D1, and E; E-cadherin; progesterone receptor
      (PR)-A and PR-B; P-glycoprotein; MLH1; and MSH2 was performed. Labeling indices
      of p53, Ki-67, and cyclins A, D1, and E in CCA were 46.4 +/- 24.3%, 52.1 +/-
      20.5%, 37.9 +/- 21.4%, 12.3 +/- 27.9%, and 8.2 +/- 22.9%, respectively. E
      cadherin was expressed in only 1 case (7.7%) of CCA, as compared to 39 cases
      (61.0%) of EMA. No CCAs were positive for PR-A and PR-B. P-glycoprotein was
      detected in seven cases (53.8%). Loss of either MLH1 or MSH2 expression occurred
      in eight cases (61.5%). High-level expression of p53, cyclin A, and P
      glycoprotein, and low-level or no expression of cyclin E, E-cadherin, PR-A, and
      PR-B was observed in CCA compared with EMA. The mechanism of cell-cycle
      regulation in endometrial CCA is different from that in EMA and may influence its
      malignant potential. Endometrial CCA is a distinct entity from EMA.

PMID- 16445665
TI  - Aggressive angiomyxoma of the female pelvis and perineum: a case series.
AB  - Aggressive angiomyxoma (AA) was first described in 1983, and fewer than 150 cases
      have been reported in the world medical literature. These tumors are benign,
      locally infiltrative mesenchymal neoplasms with a predilection for the female
      pelvis and perineum and a tendency to recur. The size of AAs at presentation
      varies considerably; however, these tumors often achieve large dimensions before
      becoming clinically symptomatic. Surgical excision remains the mainstay of
      treatment, but whether clear, tumor-free surgical margins are necessary is
      controversial. We report a cohort of six patients treated surgically during the
      past 20 years for primary or recurrent AA. Treatment, surgical margin status,
      estrogen and progesterone receptor status, and outcomes are reviewed.

PMID- 16445666
TI  - Expression of cyclin H in normal and cancerous endometrium, its correlation with
      other cyclins, and association with clinicopathologic parameters.
AB  - Cyclins are known as regulatory proteins in cell cycle. Cyclin H is a part of
      cyclin H/Cdk7/Mat1 complex, which is necessary for cellular proliferation. This
      study was designed to investigate the correlation of cyclin H expression with
      tumorigenesis of the endometrium and clinicopathologic variables.
      Immunohistochemical staining using labeled streptavidin-biotin complex was
      performed on formalin-fixed, paraffin-embedded endometrial tissues of the
      proliferative, hyperplastic, and carcinomatous types. Immunostaining for cyclins
      A, B1, D1, D3, E, H, and cyclin dependent kinase 2 were evaluated. The expression
      of cyclins A, D1, D3, and H in hyperplasia was significantly more frequent than
      those of proliferative phase and less than those of endometrioid adenocarcinoma.
      The expression of cyclin H was correlated with lymphvascular space invasion and
      clinical stage in carcinoma but not with myometrial invasion, lymph node
      metastasis, and menopause status. The expression of cyclin H could be involved in
      the transformation of the endometrium into malignancy and might be a marker for
      more proliferative and malignant features. It might be one of the biomarkers for
      determining proliferative activity in endometrial hyperplasia and endometrioid
      adenocarcinoma.

PMID- 16445667
TI  - Sensitivity to cisplatin determined by the histoculture drug response assay and
      clinical response of endometrial cancer.
AB  - This study investigated the value of the in vitro histoculture drug response
      assay (HDRA) for predicting the efficacy of chemotherapy in patients with
      endometrial cancer. Specimens were obtained from 115 patients with endometrial
      cancer treated at Keio University Hospital between 1994 and 2002. Tumor fragments
      were cultured on collagen sponge gel with cisplatin for 7 days, and cell
      viability was assessed. The cutoff value of the 50% inhibitory concentration of
      cisplatin was set at 23 microg/mL. Sensitivity of stage III or IV disease to
      chemotherapy was investigated, and differences of 5-year progression-free
      survival between patients with sensitive and resistant tumors were evaluated by
      the Kaplan-Meier method. Tumors were evaluable in 93.0% of patients (107/115).
      Among 38 patients in stages III or IV, 23 received chemotherapy containing
      cisplatin. Seven sensitive tumors did not recur, while recurrence/progression
      occurred within 6 months in 8/16 patients with tumors showing low sensitivity.
      Among stages III and IV patients, there was a significant difference of 5-year
      progression-free survival (P < 0.05) between those with tumors showing high or
      low sensitivity. Accordingly, the HDRA may predict the efficacy of chemotherapy
      for endometrial cancer.

PMID- 16445668
TI  - Expression and amplification of HER-2/neu oncogene in uterine carcinosarcomas: a
      marker for potential molecularly targeted treatment?
AB  - Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the
      poor effect of chemotherapy and radiotherapy represents an insidious problem for
      patients with metastatic or unresectable disease, and indeed, new therapeutic
      approaches are clearly required to improve survival of uterine carcinosarcoma
      patients. The HER-2 oncogene, located on chromosome 17, encodes for a tyrosine
      kinase growth factor receptor. We analyzed HER-2/neu overexpression by
      immunohistochemistry in 28 uterine carcinosarcomas. HER-2/neu amplification with
      fluorescence in situ hybridization (FISH) was tested in positive cases. The
      expression of HER-2/neu was correlated with disease-free interval and survival
      (Kaplan-Meier estimates). We observed HER-2/neu overexpression in nine cases
      (32.1%) and HER-2/neu amplification in all the four HER-2/neu 3+ score positive
      cases tested by FISH. HER-2/neu expression was not correlated with clinical
      outcome. Patients with disease limited to the uterus (stages I-II) displayed a
      significantly better disease-free survival (P= 0.004) and actuarial survival (P=
      0.01). Demonstration of HER-2/neu overexpression and amplification in uterine
      carcinosarcoma may represent the first rationale step for further investigations.
      Hence, the results of this analysis may support the challenge of a new
      therapeutic approach, which could test the role of anti-HER-2 (trastuzumab) in
      patients with advanced or metastatic uterine carcinosarcoma.

PMID- 16445669
TI  - Clinical significance of N-acetyl-L-aspartate resonance in ovarian mucinous
      cystadenoma.
AB  - Magnetic resonance spectroscopy (MRS) provides a noninvasive measurement of the
      biochemistry of living tissue. We report spectroscopy analysis of a 26-year-old
      woman affected by right ovarian lesion diagnosed as mucinous cystadenoma. MRS was
      performed by the point-resolved spectroscopy technique with a long echo time (TE)
      (136 msec). MRS measurements were performed on the two distinct component of the
      right ovarian tumor. The classification of metabolite peaks area in this study
      was performed according to the technique described by Okada et al. The features
      of proton MRS studies are discussed. As well as strongly elevated lactate and N
      acetyl-L-aspartate signals, the tumor spectrum showed lipid resonances. Proton
      MRS imaging may be helpful for the investigation of the underlying
      pathophysiology of ovarian mucinous cystadenomas.

PMID- 16445670
TI  - Ovarian endometrioid carcinoma with diffuse pigmented peritoneal keratin
      granulomas: a case report and review of the literature.
AB  - The presence of keratin granulomas in peritoneal cavity associated with ovarian
      endometrioid carcinoma, which might be related to leakage from the ovarian tumor,
      is rarely reported. Its clinical significance has not yet been well investigated.
      We report a case presenting with intermittent abdominal pain after an acute
      episode 1 month before a complex adnexal tumor was noted. Comprehensive
      cytoreductive surgery was performed. The ovarian tumor was an endometrioid
      adenocarcinoma with squamous differentiation. There were diffuse brownish flecks
      over the omental surface and pelvic peritoneum, which contained fragments of
      degenerated squamous cells, keratin, and numerous foreign body giant cells.
      Extensive multiple sections were examined for these implants. DNA flow cytometry
      and various immunostaining studies (HER-2/neu, p53, CK-7, and cytokeratin
      [AE1/AE3]) were performed. Since viable epithelial cells in the implants could be
      differentially identified against mesothelial or granulomatous components by CK-7
      staining and DNA aneuploidy was demonstrated on primary ovarian tumor, four
      courses of chemotherapy were administered. The patient has been free of disease
      for 18 months since diagnosis.

PMID- 16445671
TI  - Metastatic Hurthle cell carcinoma in the abdomen masquerading as a primary
      ovarian tumor: a case report.
AB  - Hurthle cell carcinoma, a variant of follicular carcinoma of the thyroid, has
      been regarded as an aggressive type of differentiated thyroid cancer. It is
      diagnosed histologically and regarded as a carcinoma by the presence of vascular
      invasion or capsular invasion. In this case report, a patient with a history of
      thyroid Hurthle cell carcinoma presented with what seemingly appeared to be a
      pelvic mass of gynecological origin, with a raised risk-of-malignancy index of
      567. She underwent a laparotomy which revealed the presence of multiple masses in
      the form of nodules and lumps attached to her small bowel, sigmoid colon,
      omentum, and infracolic region, without the involvement of her pelvic organs or
      para-aortic lymph nodes. At frozen section, the masses were reported to be high
      grade metastatic tumor, possibly a melanoma, unlikely to be a female genital
      tract tumor. These masses were resected along with a 15-cm section of small bowel
      and analyzed. They were diagnosed to be secondary lesions of Hurthle cell
      carcinoma of the thyroid. Hurthle cell carcinoma of the thyroid has not been
      known to be associated with the elevation of CA125 nor has it been known to
      metastasize to the small bowel and sigmoid colon.

PMID- 16445672
TI  - Carcinosarcoma arising from atypical endometriosis in a cesarean section scar.
AB  - Malignant change of endometriosis in a cesarean scar (CS) is rare. We report a
      case of carcinosarcoma arising from atypical endometriosis in a CS scar, which
      was successfully treated with complete excision of the lesion and repair of the
      abdominal wall defect with autologous skin-muscle flap graft. A 41-year-old woman
      presented with a recurrent endometriosis in a CS scar. Within 16 years it changed
      from benign to atypical endometriosis and finally to carcinosarcoma after three
      operations. Complete excision of the tumor was performed, with a big defect of
      abdominal wall successfully repaired by autologous pedicle skin-muscle graft. The
      diagnosis of carcinosarcoma arising from atypical endometriosis was confirmed
      histologically. The lesion recurred 6 months after the fourth operation. She died
      of disease 15 months after the fourth operation. This case demonstrated that long
      standing recurrent scar endometriosis could undergo malignant changes and should
      be made aware. The primary treatment is complete surgical excision.

PMID- 16445673
TI  - A case of Sertoli-Leydig cell tumor in a postmenopausal woman.
AB  - Sertoli-Leydig cell tumor belongs to the group of sex cord-stromal tumors of the
      ovary. These neoplasms account for less than 0.5% of all ovarian tumors and are
      more often encountered in young women between the ages of 20 and 30 years who
      usually become virilized. We described an unusual case of Sertoli-Leydig cell
      tumor in a postmenopausal women who presented with a solid right pelvic mass, a
      large amount of ascites, and laboratory tests revealing an elevated CA125, all
      suggesting a pelvic malignancy. Although five similar cases of postmenopausal
      women with Sertoli-Leydig cell tumor of ovary have been reported in the
      literature, we believe that this is an useful addition to the literature.

PMID- 16445674
TI  - Large-cell neuroendocrine carcinoma of the cervix associated with cervical-type
      invasive adenocarcinoma: a report of case and discussion of histogenesis.
AB  - A case of cervical large-cell neuroendocrine carcinoma with mucinous-type
      cervical adenocarcinoma component adjacent to it is presented, and its
      histopathogenesis and clinical course are discussed under the light of the
      literature.

PMID- 16445675
TI  - Metastatic uterine leiomyosarcoma coexisting with papillary carcinoma of the
      thyroid gland.
AB  - Metastatic leiomyosarcoma to the thyroid gland has rarely been described. We
      report a 54-year-old postmenopausal woman with uterine leiomyosarcoma, who
      presented with a single "cold" nodule in the right thyroid lobe 3 months after
      hysterectomy. The lesion was identified as a papillary thyroid carcinoma. In a
      separate area of the thyroid, a 1.2-mm area of a malignant mesenchymal neoplasm
      with morphologic and immunohistochemical features of leiomyosarcoma existed.
      Seven months after thyroidectomy the patient developed micronodular lung disease
      visible on successive chest computed tomography scans, consistent with metastatic
      disease from the primary uterine leiomyosarcoma that showed very good and
      prolonged response to chemotherapy. The thyroid papillary carcinoma was likely
      the recipient of an early and possibly the first metastasis of the patient's
      uterine leiomyosarcoma. This is the first report of metastatic leiomyosarcoma
      coexisting with a primary thyroid carcinoma and supports the possibility of a
      common pathway connecting thyroid gland neoplasms and sarcomas.

PMID- 16445676
TI  - Uterine lipoma and coincidental cervical cancer: a case report.
AB  - Pure lipoma of the uterus is a rare clinical event, and only a few cases have
      been reported in the literature. Clinical symptoms and physical signs are similar
      to those found in leiomyomas. The histogenesis of these lesions is still unclear.
      However, adipose metaplasia of stromal cells or smooth muscle cells of leiomyoma
      were accepted hypothesis that explain histogenesis of lipomas of uterus. We
      report the case of a 55-year-old woman with pure uterine lipoma and coincidental
      cancer of uterine cervix.

PMID- 16445677
TI  - Use of prolene mesh in surgical treatment of tissue defects after radical
      inguinal and pelvic lymph node dissection in vulvar cancer--a brief report.
AB  - Surgery is still the procedure of choice in treatment of advanced vulvar cancer.
      Radical vulvar surgery is often associated with severe vulvar and inguinal skin
      and fat-tissue deficits resulting from wide "butterfly" shape resection. Primary
      closure of large vulvar and inguinal defects is hampered by lack of tissue. The
      study presents the case of using prolene mesh in filling up the tissue defects
      over femoral vein and artery after radical excision of enlarged inguinal
      superficial, femoral, and pelvic nodes to prevent vessels in hiatus saphenus. It
      is the first report describing the use of prolene mesh in such a procedure.

PMID- 16445678
TI  - Perioperative morbidity and mortality of gynecological oncologic surgery in
      elderly women.
AB  - The study compares the perioperative morbidity and mortality rates of elderly (>
      or =70 years) and younger (< 70 years) patients. The study cohort consisted of
      171 women undergoing explorative laparotomy due to uterine or ovarian cancer.
      Clinical data included patients' age, comorbidities, chronic use of medications,
      body mass index (kg/m(2)), past and current surgical procedures, surgical FIGO
      stage, histologic type and number of dissected lymph nodes, optimal versus
      nonoptimal debulking, occurrence of perioperative complications, and
      postoperative hospital stay (days). Participants were divided to 108 (63.2%)
      patients with uterine cancer and 63 (36.8%) patients with ovarian cancer. Women
      having uterine cancer were further subdivided to those <70 years of age (72
      women, 66.7%) and those > or =70 years of age (36 women, 33.3%). Women with
      ovarian cancer were subdivided to those <70 years of age (48 women, 76.2%) and
      those > or =70 years of age (15 women, 23.8%). Excluding the occurrence of
      postoperative ileus and poorly controlled hypertension in the elderly subgroup of
      women with uterine cancer, the rate of early postoperative complications was
      similar between the two subgroups. Chronological age by itself should not be a
      contraindication for the treatment of elderly women with gynecological malignancy
      since it is a poor predicting factor for perioperative morbidity.

PMID- 16445679
TI  - Systematic nerve-sparing radical hysterectomy technique.

PMID- 16445682
TI  - The ins and outs of CD1 molecules: bringing lipids under immunological
      surveillance.
AB  - An emerging area of investigation is the role of lipids as immunological
      antigens. CD1 glycoproteins comprise a family of molecules that are specialized
      for presenting lipids, glycolipids and lipopeptides to T lymphocytes. Variations
      in the cytoplasmic tail sequences of CD1 isoforms lead to differential
      association with adaptor proteins and consequently divergent routes of
      intracellular trafficking, resulting in surveillance of distinct cellular sites
      for binding lipid antigens. CD1 molecules efficiently gain access to lipids from
      intracellular microbial pathogens in endosomal compartments, and the trafficking
      and lipid-binding specialization of CD1 isoforms may correlate with the endosomal
      segregation of structurally distinct lipids. Endosomal trafficking is also
      critical for CD1d molecules to load antigenic self-lipids that are presented to
      autoreactive CD1d-restricted natural killer (NK)T cells and is required for the
      positive selection of these unique T cells. Recent studies reveal a key role for
      accessory proteins that facilitate the uptake of lipid antigens by CD1 molecules.
      These include lysosomal lipid-transfer proteins, such as the saposins, and
      apolipoprotein E, the major serum factor that binds and delivers extracellular
      lipids to antigen-presenting cells. These advances in understanding the CD1 lipid
      antigen presentation system raise new considerations about the role of the immune
      response in lipid-related diseases.

PMID- 16445683
TI  - Integrin trafficking and the control of cell migration.
AB  - In the late 1980s and early 1990s, the observation that certain integrin
      heterodimers are continually internalized from the plasma membrane into endosomal
      compartments and subsequently recycled back to the cell surface indicated that
      the endocytic and recycling pathways have the potential to exert minute-to-minute
      control over integrin function. This insight has prompted others to study the
      regulation of integrin trafficking in more detail. This review aims to summarize
      the findings of studies revealing the molecular mechanisms controlling integrin
      traffic, particularly those providing indications as to how these processes
      contribute to cell migration and tumour cell invasiveness.

PMID- 16445684
TI  - Function and mechanism of action of Dictyostelium Nramp1 (Slc11a1) in bacterial
      infection.
AB  - Dictyostelium amoebae are professional phagocytes, which ingest bacteria as the
      principal source of food. We have cloned the Dictyostelium homologue of human
      natural resistance-associated membrane protein 1 (Nramp1) [solute carrier family
      11 member 1 (Slc11a1)], an endo-lysosomal membrane protein that confers on
      macrophages resistance to infection by a variety of intracellular bacteria and
      protozoa. The Dictyostelium Nramp1 gene encodes a protein of 53 kDa with 11
      putative transmembrane domains. The Nramp1 gene is transcribed during the growth
      phase and downregulated to barely detectable levels upon starvation. To gain
      insights into their intracellular localization, we fused Nramp1 or the vatB
      subunit of the V-H(+)ATPase with green fluorescent protein and expressed in
      cells. Green fluorescent protein-vatB was inserted in membranes of all acidic
      compartments and the contractile vacuole network and decorated macropinosomes and
      phagosomes. Green fluorescent protein-Nramp1 decorated macropinosomes and
      phagosomes, in addition to intracellular vesicular compartments positive for
      endosomal SNARE protein Vti1 or vacuolin, a marker of the exocytic pathway.
      Nramp1 disruption generated mutants that were more permissive hosts than wild
      type cells for intracellular growth of Legionella pneumophila and Micobacterium
      avium. Nramp1 overexpression protected cells from L. pneumophila infection.
      Evidence is provided that Nramp1 transports metal cations out of the
      phagolysosome in an ATP-dependent process and that L. pneumophila and M. avium
      use different mechanisms to neutralize Nramp1 activity.

PMID- 16445685
TI  - The mechanism of Salmonella entry determines the vacuolar environment and
      intracellular gene expression.
AB  - Macrophages are an important intracellular niche for Salmonella particularly for
      systemic infection. The interaction of Salmonella with these cells is mediated by
      two type III secretion systems (TTSS), encoded on Salmonella pathogenicity
      islands 1 and 2 (SPI1, SPI2), which mediate distinct phases of the pathogen-host
      cell interaction. The SPI1 TTSS mediates invasion whereas the SPI2 TTSS is
      required for intramacrophage survival. Importantly, however, Salmonella can enter
      macrophages by either SPI1-dependent invasion or host cell-mediated phagocytosis.
      Here, we investigated how the mechanism of internalization affects the
      intracellular environment and TTSS gene expression. Intracellular bacterial
      survival depended on the method of entry, because complement-opsonized and SPI1
      induced Salmonella initiated replication within 8 h whereas immunoglobulin G
      (IgG)-opsonized and non-opsonized Salmonella were initially killed. Analysis of
      vacuolar pH showed that acidification of the Salmonella-containing vacuole
      occurred more rapidly for non-opsonized or SPI1-induced Salmonella compared with
      IgG-opsonized or complement-opsonized Salmonella. Finally, quantitative
      polymerase chain reaction was used to compare the transcriptional profiles of
      selected SPI1 and SPI2 regulon genes. We found that the magnitude of SPI2 gene
      induction depended on the mechanism of internalization. Unexpectedly, SPI1 genes,
      which are rapidly downregulated following SPI1-mediated invasion, were induced
      intracellularly following phagocytic uptake. These results reveal another level
      of complexity in pathogen-macrophage interactions.

PMID- 16445686
TI  - Recycling to the plasma membrane is delayed in EHD1 knockout mice.
AB  - EHD1 is a member of the EHD family that contains four mammalian homologs. Among
      the invertebrate orthologs are a single Drosophila and Caenorhabditis elegans
      proteins and two plant members. They all contain three modules, a N-terminal
      domain that contains nucleotide-binding motifs, a central coiled-coil domain
      involved in oligomerization and a C-terminal region that harbors the EH domain.
      Studies in C. elegans and EHD1 depletion by RNA interference in human cells have
      demonstrated that it regulates recycling of membrane proteins. We addressed the
      physiological role of EHD1 through its inactivation in the mouse. Ehd1 knockout
      mice were indistinguishable from normal mice, had a normal life span and showed
      no histological abnormalities. Analysis of transferrin uptake in Ehd1(-/-)
      embryonic fibroblasts demonstrated delayed recycling to the plasma membrane with
      accumulation of transferrin in the endocytic recycling compartment. Our results
      corroborate the established role of EHD1 in the exit of membrane proteins from
      recycling endosomes in vivo in a mouse model.

PMID- 16445687
TI  - Dynamics of MAL2 during glycosylphosphatidylinositol-anchored protein
      transcytotic transport to the apical surface of hepatoma HepG2 cells.
AB  - Delivery of glycosylphosphatidylinositol (GPI)-anchored proteins to the apical
      surface takes place by transcytosis in hepatocytes and also probably in
      epithelial Madin-Darby canine cells. The integral protein MAL2 was demonstrated
      to be essential for basolateral-to-apical transcytosis in hepatoma HepG2 cells.
      Reduction of endogenous MAL2 levels impedes cargo delivery to the apical
      membrane, but, paradoxically, cargo does not accumulate in the subapical
      compartment where MAL2 predominantly resides but in distant endosome elements. To
      understand how transcytosis can be apparently mediated at a distance, we have
      analyzed the dynamics of machinery and cargo by live-cell imaging of MAL2 and
      transcytosing CD59, a GPI-anchored protein, in HepG2 cells. MAL2 was revealed as
      being a highly dynamic protein. Soon after basolateral endocytosis of CD59, a
      fraction of MAL2 redistributed into peripheral vesicular clusters that
      concentrated CD59 and that were accessible to transferrin (Tf) receptor, a
      basolateral recycling protein. Following Tf receptor segregation, the clusters
      fused in a MAL2(+)globular structure and moved toward the apical surface for CD59
      delivery. All these processes were impaired in cells with reduced MAL2 content.
      Other GPI-anchored proteins examined behave similarly. As MAL2 is expressed by
      many types of epithelia, the sorting events described herein are probably of
      quite general utility.

PMID- 16445688
TI  - Targeting of proteins of the striatin family to dendritic spines: role of the
      coiled-coil domain.
AB  - Striatin, SG2NA and zinedin, the three mammalian members of the striatin family
      are multimodular WD-repeat, calmodulin and calveolin-binding proteins. These
      scaffolding proteins, involved in both signaling and trafficking, are highly
      expressed in neurons. Using ultrastructural immunolabeling, we showed that, in
      Purkinje cells and hippocampal neurons, SG2NA is confined to the somatodendritic
      compartment with the highest density in dendritic spines. In cultured hippocampal
      neurons, SG2NA is also highly concentrated in dendritic spines. By expressing
      truncated forms of HA-tagged SG2NAbeta, we demonstrated that the coiled-coil
      domain plays an essential role in the targeting of SG2NA within spines.
      Furthermore, co-immunoprecipitation experiments indicate that this coiled-coil
      domain is also crucial for the homo- and hetero-oligomerization of these
      proteins. Thus, oligomerization of the striatin family proteins is probably an
      obligatory step for their routing to the dendritic spines, and hetero
      oligomerization explains why all these proteins are often co-expressed in the
      neurons of the rat brain and spinal cord.

PMID- 16445689
TI  - Physical factors that affect the number and size of Golgi cisternae.
AB  - Despite continual membrane reorganization in the Golgi complex, the number of
      cisternae in a Golgi stack is a stable parameter. The cisternal number is
      conserved within any given cell line and also after Golgi reassembly, e.g.
      following brefeldin-A-induced disruption. However, the factors that determine the
      cisternal number in a single Golgi stack remain to be fully determined. We
      propose a simple mechanical model of the Golgi stack and present a theoretical
      analysis of different physical factors that may affect the number of cisternae in
      a Golgi stack. The model takes into account the Golgi membrane bending
      elasticity, which is related to the membrane curvature, and the adhesion, which
      holds the cisternae together. The analysis shows that the equilibrium
      configuration of the Golgi stack can be regarded as a balance between these two
      effects - the adhesion, which tends to increase the number of cisternae, is
      opposed by the membrane resistance to bending, which does not favor highly curved
      cisternal rims. The adhesion strength that is needed to hold together a typical
      stack is calculated. In addition, the model is used to analyze changes in the
      cisternal numbers as a controlled traffic wave enters a Golgi stack and increases
      the amount of the membrane in that stack.

PMID- 16445690
TI  - Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age
      associated pathologies.
AB  - Human epidemiological studies point to an association of hypocatalasemia and an
      increased risk of age-related disease. Unfortunately, the cellular and molecular
      manifestations of hypocatalasemia are only poorly understood. In this analysis,
      we have extensively characterized hypocatalasemic human fibroblasts and report
      that they amass hydrogen peroxide and are oxidatively damaged. Protein and DNA
      alike are affected, as are functioning and biogenesis of peroxisomes - the
      subcellular organelles which normally house catalase. Despite these pathologies
      and their relative inability to grow, the cells do not appear to be intrinsically
      senescent. With the goal of restoring oxidative balance and perhaps reversing
      some of the accumulated damage to critical cellular components, we transduced
      hypocatalasemic fibroblasts with a form of catalase specifically designed to
      efficiently traffic to peroxisomes. We show the strategy is extremely effective,
      with dramatic reductions seen in cellular hydrogen peroxide levels. Future
      longitudinal studies aimed at examining the effects of a more continuous and long
      term protein therapy may now commence.

PMID- 16445692
TI  - Amino acids, arginase and nitric oxide in vascular health.
AB  - 1. Nitric oxide (NO) plays a fundamental role in the vasculature because of its
      diverse influence in vascular protection, including its well-reported
      antiproliferative, anti-inflammatory, antithrombotic and vasodilator effects. In
      many vascular disease states, NO production is reduced as a result of endothelial
      dysfunction, in part caused by a decrease in substrate (L-arginine) availability.
      2. The role of L-arginine and other amino acids important in nitrogen balance has
      been re-examined in the context of their effects on vascular health. The
      metabolism of L-arginine is complex because it is involved in a plethora of other
      pathways, such as urea, creatine and agmatine production. L-Arginine
      supplementation in patients with vascular disease is well reported to benefit
      patients therapeutically because of its effect on both NO-dependent and 
      independent mechanisms. 3. L-Arginine availability depends on the flux of other
      amino acids in the body, including L-glutamine, L-glutamate, L-ornithine, L
      citrulline and L-lysine. The role of L-methionine and homocystine and their
      effect on NO also play an influential role in the body. 4. Recent data suggest
      that the key enzyme involved in the L-arginine-urea cycle, arginase, is
      coexpressed in NO-producing cells in the vasculature. In the present review, we
      examine the potential role of arginase as a therapeutic target for vascular
      health.

PMID- 16445693
TI  - Relative contribution of the prenatal versus postnatal period on development of
      hypertension and growth rate of the spontaneously hypertensive rat.
AB  - 1. To determine the relative roles of the prenatal and postnatal (preweaning)
      environment on the development of blood pressure and growth rate in the
      spontaneously hypertensive rat (SHR) of the Okamoto strain, we used combined
      embryo transfer and cross-fostering techniques between SHR and normotensive
      Wistar-Kyoto (WKY) rats to produce offspring whose development was examined
      during the first 20 weeks of life. 2. We measured litter sizes, bodyweights and
      tail-cuff blood pressures in offspring at 4, 8, 12 and 20 weeks of age. We also
      recorded heart, kidney and adrenal weights at 20 weeks of age, when the study
      concluded. 3. We found that both the in utero and postnatal environments provided
      by the SHR mother could significantly affect WKY rat offspring growth rates, but
      blood pressure was unaffected in this strain. In SHR offspring, the SHR maternal
      in utero and suckling period both contributed to the rate of blood pressure
      development in the SHR, but not the final blood pressure of offspring at 20 weeks
      of age. This effect was greater for male than female offspring. Organ weights
      were largely unaffected by the perinatal environment in either strain. 4. We
      conclude that although the SHR maternal in utero and immediate postnatal
      environment both contribute to the rate of blood pressure development in the SHR,
      they do not appear to contribute to the final blood pressure of offspring at
      maturity. The SHR maternal environment also alters growth rate that may, in turn,
      underlie these effects on SHR blood pressure development, particularly in males.

PMID- 16445694
TI  - Pharmacological evaluation of membrane-moderated transdermal system of glipizide.
AB  - 1. Membrane-moderated transdermal systems of glipizide were prepared using drug
      containing carbopol gel (drug reservoir) and ethyl cellulose, as well as Eudragit
      RS-100, Eudragit RL-100 (Rohm Pharma, Darmstadt, Germany) and ethylene vinyl
      acetate (EVA; 2, 9 and 19% vinyl acetate content) rate-controlling membranes, and
      were subsequently evaluated in vitro (drug content and drug permeation studies)
      and in vivo (acute and long-term hypoglycaemic activity, effect on glucose
      tolerance, biochemical and histopathological studies, skin irritation test and
      pharmacokinetic studies in mice). 2. The drug content of the systems was found to
      be more than 99%. Variations in drug permeation patterns were observed among the
      formulations containing different rate-controlling membranes. 3. The system with
      the EVA (19% vinyl acetate) rate-controlling membrane was selected for in vivo
      experiments. This transdermal system produced better improvement with respect to
      hypoglycaemic activity, glucose tolerance and tested biochemical,
      histopathological and pharmacokinetic parameters all compared with oral
      administration and exhibited negligible skin irritation. 4. The transdermal
      system successfully prevented severe hypoglycaemia in the initial hours and it
      was also effective for chronic application.

PMID- 16445695
TI  - Increase of insulin secretion by ginsenoside Rh2 to lower plasma glucose in
      Wistar rats.
AB  - 1. The aim of the present study was to clarify the role of ginsenoside Rh2 as the
      active compound in Panax ginseng root for lowering plasma glucose in animals. 2.
      Plasma glucose was assessed using the glucose oxidase method. Changes in the
      levels of insulin and C-peptide in plasma were measured by ELISA using
      commercially available kits. 3. After intravenous injection into fasting Wistar
      rats for 60 min, ginsenoside Rh2 (0.1-1.0 mg/kg) decreased plasma glucose in a
      dose-dependent manner. In parallel with the decrease in plasma glucose, increases
      in plasma insulin levels, as well as plasma C-peptide, were observed in rats
      receiving the same treatment. These effects of Rh2 were reversed by atropine (0.1
      1.0 mg/kg), but not affected by the ganglionic nicotinic antagonists pentolinium
      or hexamethonium (both at 7.5 mg/kg). 4. Disruption of synaptically available
      acetylcholine (ACh) using an inhibitor of choline uptake (hemicholinium-3; 1-10
      microg/kg) or an inhibitor of vesicular ACh transport (vesamicol; 1.5-3.5 mg/kg)
      abolished the actions of Rh2. In addition, physostigmine (0.1-0.5 mg/kg), at a
      concentration sufficient to inhibit acetylcholinesterase, enhanced the actions of
      the ginsenoside Rh2. Thus, mediation of the effects of Rh2 to enhance insulin
      secretion by ACh released from nerve terminals can be considered. 5. Blockade of
      the increase in plasma insulin and the plasma glucose-lowering action of Rh2 by 4
      diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP; 5-10 microg/kg) indicates
      the participation of muscarinic M(3) receptors. Increases in plasma C-peptide
      level induced by Rh2 were also sensitive to 4-DAMP. 6. The results of the present
      study suggest that ginsenoside Rh2 has the ability to increase insulin secretion
      as a result of the release of ACh from nerve terminals that then stimulates
      muscarinic M(3) receptors in pancreatic cells. This finding shows the mechanism
      for the plasma glucose-lowering action of ginsenoside Rh2, that is one of the
      major principles contained in P. ginseng root. Thus, ginsenoside Rh2 may be
      applied as an adjuvant for the management of diabetes.

PMID- 16445696
TI  - N-acetylcysteine abrogates acute lung injury induced by endotoxin.
AB  - 1. Acute lung injury (ALI) or acute respiratory distress syndrome is a serious
      clinical problem with high mortality. N-Acetylcysteine (NAC) is an anti-oxidant
      and a free radical scavenger. It has been reported recently that NAC ameliorates
      organ damage induced by endotoxin (lipopolysaccharide; LPS) in conscious rats.
      The present study was designed to evaluate the effects of NAC on LPS-induced ALI
      and other changes in anaesthetized rats. 2. Sprague-Dawley rats were
      anaesthetized with pentobarbital (40 mg/kg, i.p.). Endotracheal intubation was
      performed to provide artificial ventilation. Arterial pressure and heart rate
      were monitored. The extent of ALI was evaluated with the lung weight
      (LW)/bodyweight ratio, LW gain, exhaled nitric oxide (NO) and protein
      concentration in bronchoalveolar lavage (PCBAL). Haematocrit, white blood cells,
      plasma nitrate/nitrite, methyl guanidine (MG), tumour necrosis factor (TNF)-alpha
      and interleukin (IL)-1b were measured. Pathological changes in the lung were
      examined and evaluated. 3. Endotoxaemia was produced by injection of 10 mg/kg,
      i.v., LPS (Escherichia coli). Animals were randomly divided into three groups. In
      the vehicle group, rats received an i.v. drip of physiological saline solution
      (PSS) at a rate of 0.3 mL/h. The LPS group received an i.v. drip of PSS for 1 h,
      followed by LPS (10 mg/kg by slow blous injection, i.v., over 1-2 min). Rats in
      the LPS + NAC group received NAC by i.v. drip at a rate of 150 mg/kg per h (0.3
      mL/h) for 60 min starting 10 min before LPS administration (10 mg/kg by slow
      blous injection, i.v., over 1-2 min). Each group was observed for a period of 6
      h. 4. N-Acetylcysteine treatment improved the LPS-induced hypotension and
      leukocytopenia. It also reduced the extent of ALI, as evidenced by reductions in
      LW changes, exhaled NO, PCBAL and lung pathology. In addition, NAC diminished the
      LPS-induced increases in nitrate/nitrite, MG, TNF-a and IL-1b. 5. In another
      series of experiments, LPS increased the mortality rate compared with the vehicle
      group (i.v. drip of PSS at a rate of 0.3 mL/h) during a 6 h observation period. N
      Acetylcysteine, given 10 min prior to LPS, significantly increased the survival
      rate. 6. The results of the present study suggest that NAC exerts a protective
      effect on the LPS-induced ALI. The mechanisms of action may be mediated through
      the reduction of the production of NO, free radicals and pro-inflammatory
      cytokines.

PMID- 16445697
TI  - Identification of differentially expressed genes induced by angiotensin II in rat
      cardiac fibroblasts.
AB  - 1. Cardiac fibroblasts play an important regulatory role in cardiac remodelling
      by undergoing proliferation, differentiation and upregulating various gene
      products, including some cytokines and extracellular matrix (ECM) proteins. A
      highly potent mediator of cardiac remodelling is angiotensin (Ang) II. 2. In the
      present study, the suppression subtractive hybridization method was used to
      identify differentially expressed cDNAs in adult rat cardiac fibroblasts induced
      by AngII. 3. Following mRNA isolation of non-stimulated and AngII-stimulated
      cells, cDNAs of both populations were prepared and subtracted by suppression
      polymerase chain reaction. Sequencing of the partially enriched cDNAs identified
      36 genes differentially expressed, including ECM proteins (pro-alpha(1) collagen
      type III, fibronectin), structural protein (spectrin), enzyme (GTP-specific
      succinyl-CoA synthetase), transcriptional regulators (glucocorticoid-induced
      leucine zipper, inhibitor of DNA binding 3) and proteins involved in cell
      division control (cdc2) or cell signalling (insulin-like growth factor binding
      protein-3, mutant p53-binding protein, grp75, CGI-121, protein phosphatase type
      2A, tspan-2 and Sam68). 4. The diversity of genes identified in the present study
      further emphasises the central role of AngII in the regulation of cardiac
      remodelling.

PMID- 16445698
TI  - Mechanism of increased alpha-adrenoceptor-mediated contraction in small
      resistance arteries of rats with heart failure.
AB  - 1. Alterations in a(1)-adrenoceptor signalling that result in enhanced
      contraction in resistance arteries in heart failure are not well characterized.
      To clarify whether this enhanced constriction is due to Ca(2+)-dependent or 
      independent effects, we measured the phenylephrine-induced changes in [Ca(2+)](i)
      in the presence of a Rho kinase inhibitor or an inositol 1,4,5-trisphosphate
      (IP(3)) receptor inhibitor. 2. Heart failure was induced in rats by ligation of
      the left coronary artery. Changes in the internal diameter of pressurized small
      femoral arteries were examined using videomicroscopy. Phenylephrine concentration
      response curves, constructed in the presence of the Rho kinase inhibitor Y27632
      (0.3 micromol/L) or the IP(3) receptor inhibitor xestospongin C (0.3 micromol/L),
      were compared in heart failure rats and sham-operated (control) rats; fura-2
      Ca(2+) signals were measured in the arteries of both groups. 3. The heart :
      bodyweight ratio, lung : bodyweight ratio, left ventricular end-diastolic
      pressure and plasma B-type natriuretic peptide were significantly higher in heart
      failure rats compared with control rats. Phenylephrine-induced contractile
      responses and increases in [Ca(2+)](i) were significantly greater in arteries
      from heart failure rats compared with arteries from control rats. At 0.3
      micromol/L, Y27632 selectively inhibited phenylephrine-induced constrictions of
      heart failure arteries, but had no effect on the increase in [Ca(2+)](i). 4.
      Immunohistochemical staining for Rho kinase was greater in heart failure rats
      compared with control rats. 5. The degree of inhibition of both the phenylephrine
      induced constriction and the increase in [Ca(2+)](i) by xestospongin C (0.3
      micromol/L) was greater in arteries from heart failure rats than in those from
      control rats. 6. The increased contractile response to phenylephrine in arteries
      of heart failure rats results from IP(3)-dependent increases in [Ca(2+)](i) and
      from an enhanced Ca(2+) sensitivity via a Rho kinase-dependent mechanism.

PMID- 16445699
TI  - Effects of N-acetyl-L-cysteine on renal haemodynamics and function in early
      ischaemia-reperfusion injury in rats.
AB  - 1. Renal ischaemia-reperfusion (IR) severely compromises kidney function and has
      been shown to cause persistent abnormalities in intrarenal blood flow. The aim of
      the present study was to examine whether N-acetyl-L-cysteine (NAC), a thiol
      containing anti-oxidant, improves renal haemodynamics and function during early
      reperfusion in rats subjected to renal IR. 2. Male Sprague-Dawley rats were
      divided into groups receiving either isotonic saline (IR-Saline; n = 8) or NAC
      (IR-NAC; n = 8) prior to (200 mg/kg, i.p., 24 and 12 h before acute
      experimentation) and during acute renal clearance experiments (bolus 150 mg/kg
      followed by a continuous infusion of 43 mg/kg per h, i.v.). During acute
      experimentation, thiobutabarbital-anaesthetized rats were subjected to a right
      sided nephrectomy, followed by left kidney IR (40 min renal artery occlusion).
      Left kidney function and blood flow and intrarenal cortical and outer medullary
      perfusion measured by laser-Doppler flowmetry was analysed at baseline, during
      ischaemia and for 80 min of reperfusion. 3. Renal IR produced an approximate 85%
      reduction in glomerular filtration rate (GFR) and a pronounced increase in
      fractional urinary sodium excretion, throughout reperfusion, with no
      statistically significant differences between groups. 4. During reperfusion,
      total renal blood flow and cortical and outer medullary perfusion rapidly
      returned to levels not significantly different from baseline in both groups. The
      relative increase in renal vascular resistance in response to IR was more
      pronounced in NAC-treated rats compared with saline-treated animals (P < 0.05).
      5. In conclusion, treatment with NAC did not improve kidney function during the
      first 80 min after renal IR. In addition, the marked reduction in GFR following
      reperfusion was not associated with any detectable abnormalities in intrarenal
      perfusion.

PMID- 16445700
TI  - Expression and functional activity of breast cancer resistance protein (BCRP,
      ABCG2) transporter in the human choriocarcinoma cell line BeWo.
AB  - 1. Breast cancer resistance protein (BCRP, ABCG2) is a drug efflux transporter
      that is believed to affect the drug disposition of several drugs and xenobiotics.
      In the present study, we evaluated the localization and functional expression of
      BCRP in the human choriocarcinoma cell line BeWo, an in vitro model of the human
      trophoblast, and compared it with the expression of P-glycoprotein (MDR1, ABCB1)
      as the most widely studied placental transporter. In addition, the expression of
      BCRP at the mRNA level was compared with that of MDR1 in the human term placenta.
      2. Western blotting analysis revealed high endogenous expression of BCRP protein
      in BeWo cells. Using indirect immunofluorescence microscopy, we found that the
      BCRP transporter appears to be localized predominantly at the apical plasma
      membrane. Functional studies showed a significant effect of the BCRP inhibitors
      GF120918 (5 micromol/L) and Ko143 (1 micromol/L) on mitoxantrone accumulation
      and, thus, confirmed efflux activity of BCRP in BeWo cells. 3. Using absolute
      mRNA quantification with real-time reverse transcription-polymerase chain
      reaction, we found high expression of BCRP in BeWo cells, whereas no transcript
      of MDR1 (P-glycoprotein), the most extensively studied drug transporter, was
      detected. 4. In the human placenta, BCRP was localized predominantly in the
      syncytiotrophoblast layer; however, immunopositivity for the BXP-21 antibody was
      also observed in fetal vessels of the chorionic villi. The number of BCRP
      transcripts in the human term placenta was found to be more than 10-fold higher
      compared with the expression of MDR1. 5. In conclusion, we suggest that BeWo
      cells could serve as a suitable in vitro model to study trans-trophoblast
      transport of BCRP substrates and that placental BCRP can play an important role
      in preventing the accumulation of potentially toxic xenobiotics in the
      trophoblast cells.

PMID- 16445701
TI  - Effect of heparin on activation of platelet function in patients during
      radiofrequency catheter ablation.
AB  - 1. Thromboembolism occurs in 0.4-2.0% of patients undergoing radiofrequency
      catheter ablation (RFCA). Some studies have shown that treatment with heparin
      inhibits the activation of coagulation and fibrinolysis. No study has directly
      measured the activation of platelet aggregation to investigate the effect of
      heparin on platelet function. The purpose of the present study was to observe the
      inhibitory effect of heparin on platelet activity in patients undergoing RFCA. 2.
      Sixty-two patients with supraventricular tachycardia were observed and divided
      into a heparin-treatment group and a control group. Changes in platelet
      aggregability (PAG) and thromboxane B(2) (TXB(2)) in the blood samples of all
      patients at different times (before, after electrophysiological study,
      immediately after and 10 and 30 min after the RFCA procedure) were observed. 3.
      No indication of clinically symptomatic thromboembolism and no major differences
      in baseline characteristics and procedure were apparent in either group. The
      levels of PAG and TXB(2) were all clearly increased after the
      electrophysiological study (all P < 0.05). Immediately after RFCA, PAG and TXB(2)
      levels were significantly increased in both groups and remained elevated 30 min
      after the procedure (all P < 0.05). In the heparin-treatment group, the increases
      in PAG (54.69 +/- 3.24%) and TXB(2) (29.01 +/- 1.84%) caused by RFCA were lower
      than changes observed in the control group (70.92 +/- 3.45 and 44.70 +/- 3.28%,
      respectively; both P < 0.01). Moreover, treatment with heparin normalized the
      elevated level of PAG 30 min after RFCA more clearly. 4. The results of the
      present study suggest that intravenous heparin treatment during the operation
      inhibits the activation of platelets induced by RFCA.

PMID- 16445702
TI  - An aldosterone-related system in the ventrolateral medulla oblongata of
      spontaneously hypertensive and Wistar-Kyoto rats.
AB  - 1. The actions of aldosterone include mediation of vasoconstriction, vascular
      fibrosis, endothelial dysfunction and sodium retention. These actions can
      contribute to hypertension. Recent studies implicate an abnormal aldosterone
      hormonal system in the brain in hypertension. However, the study of central
      aldosterone actions is still in its infancy, as the exact location and abundance
      of its components in the brain are uncertain. 2. We aimed to detect components of
      the aldosterone cascade in the regions of the ventrolateral medulla oblongata
      (VLM)-containing neurons that regulate blood pressure and to see whether there
      are quantitative differences in these components between the spontaneously
      hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat models. Tissues
      from four regions of the brainstem, namely, the rostral and caudal ventrolateral
      medulla (RVLM and CVLM, respectively), rostral pressor area and caudal pressor
      area, were examined. We measured mRNA expression of aldosterone synthase,
      mineralocorticoid receptor (MR1), 12-lipoxygenase (12-LO), serum- and
      glucocorticoid- inducible kinase and K-ras in male rats. Gene expression levels
      were measured using real-time reverse transcription-polymerase chain reaction. 3.
      We detected all aldosterone components in all regions of the VLM. The K-ras
      levels were not significantly different in any of the regions. Expression of MR1
      mRNA was lower in the RVLM of SHR (n = 5) compared with WKY rats (n = 5; t =
      4.590; P = 0.002) and 12-LO mRNA levels were lower in the CVLM in SHR (n = 6)
      compared with WKY rats (n = 7; P = 0.04). Thus, we have shown for the first time
      that components of the aldosterone cascade are present in the VLM. Our results
      suggest that there may be a differential gene expression profile in the brainstem
      for genetic hypertension.

PMID- 16445703
TI  - Effects of a single, short intravenous dose of acetyl-L-carnitine on pattern
      reversal visual-evoked potentials in cirrhotic patients with hepatic
      encephalopathy.
AB  - 1. In animals and in cultured neurons, L-carnitine and acetyl-L-carnitine (ALCAR)
      have been shown to counteract some of the toxic effects of ammonia. In order to
      detect similar properties in humans, we studied neuronal function after ALCAR
      administration in cirrhotics with hepatic encephalopathy (HE). 2. Eighteen
      cirrhotic patients with persistent HE and hyperammonaemia were investigated in
      the present study and six subjects with a prior transient ischaemic attack were
      used as controls. 3. The prominent positive component that occurs approximately
      100 msec after the pattern reversal (P100) latencies of visual-evoked potentials
      were used to evaluate neuronal function. At first, the P100 latency was measured
      in six cirrhotic patients with HE and in the six controls before the
      administration of 0.5 g ALCAR in 50 mL isotonic saline (infusion rate 10 mL/min)
      and 15, 30, 60 and 90 min later. 4. A significant reduction in P100 latencies was
      identified 30 min after ALCAR infusion in HE patients, whereas no differences
      were observed in controls. 5. Thereafter, the P100 latency was evaluated in the
      12 other cirrhotic patients with HE only before and 30 min after ALCAR infusion.
      The mean of the P100 latencies measured in these subjects was significantly
      shorter after ALCAR infusion compared with values obtained before ALCAR
      administration (mean (+/-SD) 130.78 +/- 5.50 vs 136.08 +/- 6.45 msec,
      respectively; P = 0.0013). 6. The present study suggests that a single
      intravenous dose of ALCAR may transiently improve neuronal function in cirrhotic
      patients with persistent HE and hyperammonaemia.

PMID- 16445704
TI  - Prostacyclin causes splenic dilation and haematological change in dogs.
AB  - 1. The effect of vasodilators on spleen volume and the blood storage function is
      not yet well elucidated. To this end, in the present study the effects of
      prostacyclin, a potent vasodilator, on splenic diameter and blood cell
      concentrations in arterial and splenic venous blood were evaluated in
      anaesthetized dogs. 2. The main splenic artery and vein were dissected for
      measurement of splenic arterial blood flow and intra-arterial administration and
      for sampling of splenic venous blood, respectively. The diameter of the spleen
      was measured continuously by sonomicrometry. Counts of white blood cells (WBC),
      red blood cells (RBC) and platelets in blood sampling from the aorta and splenic
      vein were estimated by an automatic blood cell counter. 3. Bolus injections of
      prostacyclin (1-100 ng/kg) into the splenic artery produced dose-dependent
      increases in splenic arterial blood flow and splenic diameter associated with
      significant decreases in splenic venous concentrations of WBC, RBC and platelets.
      When splenic blood flow was kept constant, similar changes in splenic diameter
      and blood cell counts were observed with prostacyclin injection. 4. Splenic
      dilation and haematological changes induced by prostacyclin were relatively more
      potent than those induced by prostaglandin E(2), acetylcholine, nitroglycerin or
      isoproterenol when doses producing a comparable increase in splenic blood flow
      were compared. 5. Infusion of prostacyclin (100 ng/kg per min) into the splenic
      artery caused a marked increase in splenic diameter, with immediate reductions in
      splenic venous concentrations of WBC, RBC and platelets, followed by significant
      reductions in these cell counts in the general circulation. 6. These results
      indicate that prostacyclin produces potent and flow-independent splenic dilation
      that may contribute to a decrease in circulating blood cell concentrations.

PMID- 16445705
TI  - Activities of aqueous extracts of Mallotus oppositifolium on Shigella dysenteriae
      A1-induced diarrhoea in rats.
AB  - 1. Mallotus oppositifolium is reported to possess medicinal properties and is
      traditionally used in Cameroon for the treatment of diarrhoea. In the present
      study, we have evaluated the acute toxicity, in vitro antibacterial and in vivo
      antidiarrhoeal effects of an aqueous extract of these plant leaves. 2. Shigella
      dysenteriae A(1) (Sd1)-induced diarrhoeal rats were obtained by oral
      administration of increasing densities of the Sd1 strain isolated from bloody
      diarrhoea occurring in East Cameroon. When diarrhoea appeared, rats were treated
      for 5 consecutive days with 120, 240 or 360 mg/kg extract or norfloxacin (5.7
      mg/kg). The weight and frequencies of faeces, as well as the number of Sd1, were
      assessed during the treatment period and the death rate was recorded. 3. The M.
      oppositifolium extract was not toxic. In vitro, the minimal inhibitory and
      minimal bactericidal concentrations of the extracts were 1,172 and 9,375
      microg/mL, respectively. In vivo, 12 x 10(8) Sd1 provoked diarrhoea within 24 h,
      which was characterized by soft or liquid stools, that were moulded, smooth and
      mucus or blood coated. Diarrhoea went along with an increase in faeces weight and
      frequency (P < 0.001 by the 3rd day), as well as an increase in the bacterial
      population to a maximum on the 2nd day after infection (P < 0.05). The death rate
      was 67% by day 6. 4. Whereas norfloxacin significantly (P < 0.01) reduced Sd1
      growth, M. oppositifolium extracts (240 and 360 mg/kg) restored bacterial growth
      to its initial density and no deaths were recorded. There was a significant (P <
      0.05) reduction in stools weight and frequency with 240 mg/kg extract. 5. The
      results suggest that M. oppositifolium leaves could be a therapeutic alternative
      for bacterial aetiological diarrhoea in Central Africa, where multidrug supply
      and access to modern health centres are public health problems.

PMID- 16445706
TI  - Melatonin reduces urinary excretion of N-acetyl-beta-D-glucosaminidase, albumin
      and renal oxidative markers in diabetic rats.
AB  - 1. Increased oxidative stress has an important role in the pathogenesis of
      diabetic nephropathy. The aim of the present study was to evaluate diabetic
      nephropathy by determining markers of oxidative stress and the urinary excretion
      of N-acetyl-beta-D-glucosaminidase (NAG), albumin and to investigate the possible
      protective effects of in vivo melatonin on renal tubular oxidative damage in
      diabetic rats. 2. Twenty-six rats were randomly divided into three groups: (i)
      group I, control, non-diabetic rats (n = 9); (ii) group II, untreated diabetic
      rats (n = 8); and (iii) group III, melatonin-treated diabetic rats (n = 9). In
      groups II and III, diabetes developed 3 days after administration of a single
      dose of streptozotocin (35 mg/kg, i.p.). Thereafter, whereas the rats in group II
      received no treatment, rats in group III began to receive 10 mg/kg per day, i.p.,
      melatonin for 8 weeks. Malondialdehyde (MDA), an index of lipid peroxidation, NAG
      and microalbumin in the urine, markers of renal tubular damage, were the
      parameters used for oxidative stress-induced renal injury. Superoxide dismutase
      (SOD), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) activities were
      determined to evaluate changes in the anti-oxidant status of kidney tissue. 3. In
      untreated diabetic rats, urinary NAG, albumin and renal MDA levels were markedly
      increased compared with control rats (P < 0.0001). However, these parameters were
      reduced in diabetic rats by melatonin treatment (P < 0.0001). Urinary excretion
      of NAG was positively correlated with the microalbuminuria and renal MDA levels
      (r = 0.8; P < 0.0001). The SOD and XO activities in the untreated diabetic group
      were found to be significantly higher than those of the control group (P <
      0.0001). Superoxide dismutase and XO activities decreased in melatonin-treated
      rats compared with untreated diabetic rats (P < 0.002 and P < 0.023,
      respectively). However, the decrease did reach levels seen in control rats. There
      were no significant differences in GSH-Px activity between the three groups. 4.
      Therefore, on the basis of these data, we suggest that urinary NAG, albumin
      excretion, XO activity and MDA levels are more valuable parameters showing the
      degree of renal tubular injury than classical markers of oxidative stress,
      including SOD and GSH-Px, in diabetic rat kidneys. Melatonin has an ameliorating
      effect on oxidative stress-induced renal tubular damage via its anti-oxidant
      properties. Thus, it may be suggested that urinary NAG excretion and
      microalbuminuria may be important markers showing the degree of renal changes and
      the success of long-term treatment of renal impairment with melatonin.

PMID- 16445707
TI  - Gender disparity of streptozotocin-induced intrinsic contractile dysfunction in
      murine ventricular myocytes: role of chronic activation of Akt.
AB  - 1. Clinical, epidemiological and experimental evidence suggests a 'female
      advantage' in the progression of cardiovascular diseases, including diabetic
      cardiomyopathy. It is speculated that this 'gender bias' may be due to gender
      related differences in sex hormones and intrinsic myocardial contractile
      properties. 2. The present study was designed to examine the impact of diabetes
      and gender on cardiac contractile function and activation of the cardiac survival
      signalling molecule Akt. Short-term (2 weeks) diabetes was induced in adult mice
      of both genders with streptozotocin (STZ). Mechanical and intracellular Ca(2+)
      properties of isolated ventricular myocytes were evaluated using an IonOptix
      MyoCam system (IonOptix Corporation, Milton, MA, USA). Total and phosphorylated
      Akt were evaluated using western blot analysis. 3. Female mouse myocytes
      displayed smaller peak shortening (PS) amplitude and maximal velocity of
      shortening/relengthening (+/-dL/dt), longer time to PS and time to 90%
      relengthening compared with male counterparts. Diabetes significantly reduced PS,
      +/-dL/dt, prolonged TR(90), delayed intracellular Ca(2+) clearing and reduced
      sarcoplasmic reticulum (SR) Ca(2+) release in male mouse myocytes. All these
      abnormalities, with the exception of SR Ca(2+), release were masked by the female
      gender. 4. The negative staircase of PS with increased stimulus frequency (from
      0.1 to 5.0 Hz) and protein carbonyl damage were comparable among all animal
      groups. 5. Female gender and diabetes independently enhanced phosphorylation of
      Akt without affecting total Akt expression. Interestingly, STZ-induced short-term
      diabetes failed to elicit additional phosphorylation of Akt in female hearts. 6.
      In summary, the present data revealed that STZ induced impaired cardiac
      contractile function and altered intracellular Ca(2+) handling in males, but not
      females, partially due to intrinsic mechanical differences and Akt activation
      status between genders.

PMID- 16445708
TI  - Activity of Cecropia lyratiloba extract on contractility of cardiac and smooth
      muscles in Wistar rats.
AB  - 1. Brazilian forests show high diversity of medicinal plants and several are used
      in folk medicine for the treatment of hypertension and asthma. The aim of the
      present study was to investigate the effects of a methanol extract (ME) of
      Cecropia lyratiloba and its flavonoid fraction (FF) on the contractility of
      cardiac, vascular and tracheal smooth muscles. 2. Twitches of rat papillary
      muscles were obtained with electrical stimulation and were recorded before and
      after exposure to increasing concentrations of ME and FF. 3. Cardiac depression
      was induced by FF. At 500 microg/mL FF, the amplitude of twitches was reduced to
      56.7 +/- 5.1% of control values (P < 0.05). 4. The contractile response to a
      single concentration of adrenaline (10 micromol/L) was measured before and after
      exposure to ME and FF in rat aorta rings with intact endothelium. Both ME and FF
      inhibited adrenaline-induced contractions of the aorta in a concentration
      dependent manner. Adrenaline-induced contractions were reduced to 46.4 +/- 9.9
      and 34.2 +/- 6.9% (P < 0.05) of control in the presence of 500 microg/mL ME and
      FF, respectively. 5. The flavonoids isolated from FF, namely isoorientin and a
      mixture of orientin and isovitexin, were also tested in the aorta. These
      flavonoid do not seem to be responsible for the vasorelaxant effects of ME and
      FF. 6. No changes were observed in acetylcholine-precontracted trachea when
      exposed to ME or FF. 7. Endothelium-dependent vasodilation induced by FF is
      likely to be mediated by the release of nitric oxide because vascular relaxation
      was abolished in the presence of N(omega)-nitro-L-arginine methyl ester, an
      inhibitor of nitric oxide synthase. 8. In conclusion, vascular relaxation induced
      by ME and FF could explain the traditional use of the extract of C. lyratiloba
      for treatment of arterial hypertension.

PMID- 16445709
TI  - Activation of L-arginine transport in undialysed chronic renal failure and
      continuous ambulatory peritoneal dialysis patients.
AB  - 1. Treatment with haemodialysis and continuous ambulatory peritoneal dialysis
      (CAPD) presents different pathophysiological profiles and it has been suggested
      that clinical outcome in chronic renal failure may depend on the mode of
      dialysis. The transport of L-arginine, a precursor of nitric oxide, into blood
      cells is increased in uraemic patients on haemodialysis. The present study was
      designed to investigate L-arginine transport into red blood cells (RBC) in
      uraemic patients not yet on dialysis and on CAPD therapy. 2. Eleven uraemic
      patients not yet on dialysis and 17 on CAPD were included in the study. L
      Arginine transport into RBC and plasma and RBC amino acid profiles were analysed
      in these sets of patients. 3. L-Arginine transport via system y(+), but not
      y(+)L, into RBC, was significantly increased in undialysed uraemic patients (459
      +/- 40 micromol/L per cell per h) and CAPD patients (539 +/- 61 micromol/L per
      cell per h) compared with controls (251 +/- 39 micromol/L per cell per h). High
      pressure liquid chromatography measurements demonstrated low levels of plasma L
      arginine in uraemic patients both on CAPD (54 +/- 3 micromol/L) and not yet on
      dialysis (80 +/- 6 micromol/L) compared with control subjects (146 +/- 14
      micromol/L). 4. Our findings provide the first evidence that uraemic patients not
      yet on dialysis and on CAPD present with an activation of L-arginine transport
      via system y(+) into RBC associated with reduced plasma levels of L-arginine.

PMID- 16445710
TI  - Protective effects of L-carnitine on myoglobinuric acute renal failure in rats.
AB  - 1. Muscle injury (rhabdomyolysis) is one of the causes of acute renal failure
      (ARF). Iron, free radicals and nitric oxide (NO) play a critical role in the
      pathogenesis of glycerol-induced myoglobinuric ARF. L-Carnitine is an anti
      oxidant and prevents the accumulation of end-products of lipid peroxidation.
      Therefore, the aim of the present study was to investigate the effects of L
      carnitine on myoglobinuric ARF induced by intramuscular (i.m.) hypertonic
      glycerol injection. 2. Sprague-Dawley rats were divided into three groups. Rats
      in group 1 (n = 8) were given saline, whereas those in groups 2 (n = 10) and 3 (n
      = 10) were injected with glycerol (10 mL/kg, i.m.). Concomitant with and 24 h
      after glycerol injection, L-carnitine (200 mg/kg, i.p.) was administered to group
      3 rats. Forty-eight hours after glycerol injection, blood samples and kidney
      tissues were taken from anaesthetised rats. 3. Plasma creatine kinase (CK)
      activity, urea, creatinine and NO levels, as well as kidney tissue superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activity
      and malondialdehyde (MDA) and glutathione (GSH) levels, were determined. In the
      kidney tissue, histopathological changes and iron accumulation in the tubular
      epithelium were also investigated. 4. Glycerol treatment caused severe ARF: a
      marked renal oxidative stress, significantly increased CK activity, urea and
      creatinine levels and decreased plasma NO levels. Histopathological findings in
      group 2 rats confirmed that there was renal impairment by cast formation and
      tubular necrosis and a marked increase in iron accumulation in the tubular
      epithelium. All these factors were significantly improved by L-carnitine
      supplementation. 5. These results may indicate that L-carnitine treatment
      protects against functional, biochemical and morphological damage and iron
      accumulation in glycerol-induced myoglobinuric ARF in rats. In this model, the
      protective effect of L-carnitine treatment may provide a new insight into the
      treatment of rhabdomyolysis-related ARF.

PMID- 16445711
TI  - Meta-analysis of the differences in the time to onset of action between
      rocuronium and vecuronium.
AB  - 1. The aim of the present study was to conduct a meta-analysis of the magnitude
      of differences in the onset of action (T(max)) between rocuronium and vecuronium.
      2. A search was made in PubMed, EMBASE Drugs and Pharmacology, Cochrane
      Controlled Trials Register and Cochrane Database on Systematic Reviews. Studies
      comparing the T(max) at the adductor policies between rocuronium and vecuronium
      administered as an intravenous bolus were included in the study. Twenty-nine
      effect sizes obtained from 21 studies were included. 3. The result of the meta
      analysis of differences was -57.9 s (95% confidence interval -71.4 to -44.3 s),
      favouring rocuronium over vecuronium. The smallest difference in T(max) between
      these neuromuscular-blocking agents was observed in children (-19.1 s). The
      difference in T(max) between rocuronium and vecuronium in female patients was 
      38.7 s. The difference in T(max) between rocuronium and vecuronium measured by
      electromyography was approximately 50% shorter than that determined by
      acceleromyography or mechanomyography. In a subanalysis between rocuronium 600
      mg/kg versus vecuronium 100 mg/kg, the difference in T(max) between them was very
      similar to that obtained in the general meta-analysis. 4. According to
      subanalyses of patient age and sex, drug dose and neuromuscular monitoring
      systems, the T(max) of rocuronium was approximately 20-70 s faster than that of
      vecuronium.

PMID- 16445712
TI  - Early activation of internal medial smooth muscle cells in the rabbit aorta after
      mechanical injury: relationship with intimal thickening and pharmacological
      applications.
AB  - 1. Smooth muscle cells (SMC) participate in both inflammatory and
      dedifferentiation processes during atherosclerosis, as well as during mechanical
      injury following angioplasty. In the latter, we studied medial SMC
      differentiation and inflammation processes implicated early after de
      endothelialization in relation to mechanical stresses. We hypothesized that
      activation of a subpopulation of SMC within the media plays a crucial role in the
      early phase of neointimal formation. 2. For this purpose, we used a rabbit model
      of balloon injury to study activation and differentiation of medial SMC in the
      early time after denudation and just before neointima thickening. Inflammation
      was evaluated by the expression of vascular cell adhesion molecule (VCAM)-1,
      integrin alpha4beta1 and nuclear factor (NF)-kB. Myosin isoforms and 2P1A2
      antigen, a membrane protein expressed by rabbit dedifferentiated SMC, were used
      as markers of differentiation. 3. On day 2 after de-endothelialization, VCAM-1,
      alpha4beta1 and NF-kB were coexpressed by a well-defined subpopulation of SMC of
      the internal part of the media, in the vicinity of the blood stream. At the same
      time, the majority of SMC throughout the media expressed non-muscle myosin heavy
      chain-B (nm-MHC-B) and 2P1A2 antigen. On day 7, when intimal thickening appeared,
      SMC of the media were no longer activated, whereas some intimal SMC expressed the
      activation markers. Thus, after de-endothelialization, early dedifferentiation
      occurs in most of the medial SMC, whereas activation concerned only a
      subpopulation of SMC located in the internal media. Using the T-type voltage
      operated calcium channel blocker mibefradil (0.1-1 micromol/L) in SMC culture, we
      showed that this agent exhibited an antiproliferative effect in a dose-dependent
      manner only on undifferentiated cells. 4. In conclusion, the results suggest that
      the activated SMC represent cells that are potentially able to migrate and
      participate in the intimal thickening process. Thus, the medial SMC inflammatory
      process, without any contribution of inflammatory cells, may represent a major
      mechanism underlying the development of intimal thickening following mechanical
      stress. In humans, inhibition of T-type calcium channels may be a tool to prevent
      the early proliferation step leading to neointimal formation.

PMID- 16445713
TI  - Genes, calcium and modifying factors in hypertrophic cardiomyopathy.
AB  - 1. Familial hypertrophic cardiomyopathy (FHC) is a primary disorder of the
      myocardium characterized by remarkable diversity in clinical presentations,
      ranging from no symptoms to severe heart failure and sudden cardiac death. 2.
      Over the past 15 years, at least 11 genes have been identified, defects of which
      cause FHC. Most of these genes encode proteins that comprise the basic
      contractile unit of the heart (i.e. the sarcomere). 3. Genetic studies are now
      beginning to have a major impact on the diagnosis in FHC, as well as in guiding
      treatment and preventative strategies. Although much is known about which genes
      cause disease, relatively little is known about the molecular steps leading from
      the gene defect to the clinical phenotype and what factors modify the expression
      of the mutant genes. 4. Concurrent studies in cell culture and animal models of
      FHC are now beginning to shed light on the signalling pathways involved in FHC
      and the role of both environmental and genetic modifying factors. Calcium
      dysregulation appears to be important in the pathogenesis of FHC. 5.
      Understanding these basic molecular mechanisms will ultimately improve our
      knowledge of the basic biology of heart muscle function and will therefore
      provide new avenues for diagnosis and treatment not only for FHC, but also for a
      range of human cardiovascular diseases.

PMID- 16445714
TI  - Reactive oxygen species in cardiac signalling: from mitochondria to plasma
      membrane ion channels.
AB  - 1. Reactive oxygen species (ROS) have been considered deleterious to cell
      function and there is good evidence to suggest that they play a role in the
      pathophysiology of a number of cardiac disease states. However, ROS are also now
      being recognized as important regulators of cell function by altering the redox
      state of proteins. 2. Possible sources of production of ROS in cardiac myocytes
      are the mitochondria and nicotinamide adenine dinucleotide phosphate-oxidase. The
      generation of ROS and anti-oxidant defence mechanisms in the heart are discussed.
      3. The evidence for a role for ROS in the development of disease states, such as
      atherosclerosis, ischaemia, cardiac hypertrophy and hypertension, is presented.
      It is now recognized that cardiac ion channel function is regulated by ROS.
      Implications with respect to cardiac arrhythmia are discussed.

PMID- 16445715
TI  - Convergence of glucose- and fatty acid-induced abnormal myocardial excitation
      contraction coupling and insulin signalling.
AB  - 1. Myocardial insulin resistance and abnormal Ca(2+) regulation are hallmarks of
      hypertrophic and diabetic hearts, but deprivation of energetic substrates does
      not tell the whole story. Is there a link between the aetiology of these
      dysfunctions? 2. Diabetic cardiomyopathy is defined as phenotypic changes in the
      heart muscle cell independent of associated coronary vascular disease. The
      cellular consequences of diabetes on excitation-contraction (E-C) coupling and
      insulin signalling are presented in various models of diabetes in order to set
      the stage for exploring the pathogenesis of heart disease. 3. Excess glucose or
      fatty acids can lead to augmented flux through the hexosamine biosynthesis
      pathway (HBP). The formation of uridine 5 cent-diphosphate-hexosamines has been
      shown to be involved in abnormal E-C coupling and myocardial insulin resistance.
      4. There is growing evidence that O-linked glycosylation (downstream of HBP) may
      regulate the function of cytosolic and nuclear proteins in a dynamic manner,
      similar to phosphorylation and perhaps involving reciprocal or synergistic
      modification of serine/threonine sites. 5. This review focuses on the question of
      whether there is a role for HBP and dynamic O-linked glycosylation in the
      development of myocardial insulin resistance and abnormal E-C coupling. The
      emerging concept that O-linked glycosylation is a regulatory, post-translational
      modification of cytosolic/nuclear proteins that interacts with phosphorylation in
      the heart is explored.

PMID- 16445716
TI  - Cardiac hypertrophy, substrate utilization and metabolic remodelling: cause or
      effect?
AB  - 1. Metabolic remodelling in the heart occurs in response to chronically altered
      workload and substrate availability. Recently, the importance of the metabolic
      remodelling processes inherent in the hypertrophic growth response (whether
      primary or secondary) has been recognized. 2. Altered energy demand, shifts in
      substrate utilization and increased oxidative stress are observed in the
      hypertrophic heart. Both a shift away from carbohydrate usage (i.e. insulin
      resistance) and a shift to carbohydrate usage (i.e. pressure loading) are
      associated with disturbed cardiomyocyte Ca(2+) homeostasis and the development of
      cardiac hypertrophy. 3. A change in the balance of myocardial usage of fatty acid
      and glucose substrates must entail a degree of cellular oxidative stress.
      Increased throughput of any substrate will necessarily involve a regional
      imbalance between reactive oxygen species (ROS) production and breakdown. 4. In
      addition to a number of enzyme generators of ROS at various intracellular
      locations, the heart also contains a number of endogenous anti-oxidants, to
      restrict steady state ROS levels. The balance between ROS generation and their
      elimination by endogenous anti-oxidant mechanisms plays a critical role in
      preserving cardiac function; inappropriate levels of myocardial ROS likely
      precipitate impairment of myocardial function and abnormalities in cardiac
      structure. 5. Although different metabolic adaptations are associated with
      hypertrophic responses of contrasting aetiology, there is accumulating evidence
      that the joint insults of increased production of ROS and disturbed Ca(2+)
      handling in the cardiomyocyte comprise the primary lesion. These molecular
      signals operate together in a feed-forward mode and have the capacity to inflict
      substantial functional and structural damage on the hypertrophic myocardium.

PMID- 16445717
TI  - Introduction. Staphylococcal infections--whatever next?

PMID- 16445718
TI  - The importance of the development of antibiotic resistance in Staphylococcus
      aureus.
AB  - Hospital- and community-acquired Staphylococcus aureus infections pose a
      substantial burden in terms of morbidity, mortality and health care costs. The
      introduction of new antibiotics to counter this pathogen has frequently been
      closely followed by the emergence of resistant strains. Most significantly, S.
      aureus isolates resistant to beta-lactams have become common, and many of these
      are also resistant to beta-lactamase-resistant penicillins. The rapid spread of
      methicillin-resistant S. aureus (MRSA) clones across the world often results in
      hospital outbreaks, but implementation of appropriate control measures usually
      reduces prevalence to sporadic levels. However, the recent emergence of MRSA
      infections in the community, affecting patients with no established risk factors
      for MRSA acquisition, is likely to impact significantly on future strategies for
      control of nosocomial MRSA. In contrast to other antibiotic classes, S. aureus
      resistance to glycopeptides did not emerge until nearly 40 years after their
      clinical introduction, and as a result this drug class has remained the mainstay
      of treatment for MRSA infections. However, a number of vancomycin-intermediate S.
      aureus isolates have emerged worldwide and four fully resistant S. aureus
      isolates have been reported in the USA. This raises the concern that the current
      first-line treatment for MRSA infection may become ineffective in an increasing
      proportion of cases in the near future. New classes of antibiotic are urgently
      needed to treat infections with this growing population of multidrug-resistant S.
      aureus, and the recently introduced oxazolidinone linezolid and the cyclic
      lipopeptide daptomycin are welcome additions to the ever-narrowing range of
      therapies effective against this pathogen.

PMID- 16445719
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: current
      perspectives.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become a worldwide
      problem, although its prevalence varies considerably among countries. The
      epidemiology of MRSA is now changing; infections are no longer confined to the
      hospital setting, but also appear in healthy community-dwelling individuals
      without established risk factors for the acquisition of MRSA. Reported prevalence
      rates of community-acquired MRSA (CA-MRSA) vary widely among studies-largely
      because of the different definitions employed and different settings in which the
      studies have been performed. At present, molecular epidemiological definitions,
      based on staphylococcal cassette chromosome mec (SCCmec) typing and phylogenetic
      analyses of the MRSA isolates, are considered the most reliable means by which to
      distinguish between hospital-acquired MRSA (HA-MRSA) and CA-MRSA. CA-MRSA has
      been isolated predominantly from skin and soft tissue infections, such as
      abscesses, cellulitis, folliculitis and impetigo. Although CA-MRSA infections are
      usually mild, they may also be severe, and can result in hospitalisation and even
      death. CA-MRSA strains differ from the major pandemic clones of MRSA that account
      for the majority of epidemic HA-MRSA strains. Differences are found in SCCmec
      types, bacterial growth rate, and the distribution of antibiotic resistance genes
      and toxin genes. Mathematical models have shown that CA-MRSA has a high potential
      to become endemic in the community, and this will impact significantly on the
      control of MRSA in the hospital setting. Well-designed, community-based studies
      with adequate risk factor analysis are required to further elucidate the
      epidemiology of CA-MRSA and to improve strategies to control MRSA in both the
      community and hospital settings.

PMID- 16445720
TI  - The emergence of vancomycin-intermediate and vancomycin-resistant Staphylococcus
      aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is well-recognised as a major
      cause of infection in the health care setting but, even more worryingly, is now
      emerging in the community. The glycopeptides-notably vancomycin-have
      traditionally been the mainstay of treatment of MRSA but overuse has led to the
      emergence of vancomycin-intermediate and vancomycin-resistant MRSA (VISA and
      VRSA, respectively). Although the mechanisms underlying vancomycin resistance are
      not yet fully understood, changes to the bacterial cell wall-the site of action
      of the glycopeptides-are believed to be key. Recent evidence also supports the
      transfer of genetic material among bacteria as contributing to the development of
      VRSA. Based on the cases identified to date, risk factors for the development of
      VRSA may include older age, compromised blood flow to the lower limbs, and the
      presence of chronic ulcers. The true extent of the problem, however, remains to
      be determined-it is likely that many cases of VISA and VRSA infection go
      undetected because of suboptimal screening programmes and possible limitations of
      automated and non-automated detection methods. Effective screening directed at
      those patients considered to be most at risk should therefore be a priority. Not
      surprisingly, the spread of MRSA from the hospital to the community setting,
      coupled with the emergence of VISA and VRSA, has become a major cause of concern
      among clinicians and microbiologists. The treatment options available for these
      infections are now severely compromised and thus new classes of antimicrobial
      agents effective against MRSA, VISA and VRSA are urgently required.

PMID- 16445721
TI  - The efficacy and safety of daptomycin: first in a new class of antibiotics for
      Gram-positive bacteria.
AB  - In the face of increasing resistance to currently available antibiotics, there is
      a continued interest in the development of new drugs to treat Gram-positive
      infections. One such agent is the cyclic lipopeptide daptomycin-licensed in the
      USA for treatment of Gram-positive complicated skin and skin structure infections
      (cSSSIs) in 2003 and currently awaiting European approval for a similar
      indication (complicated skin and soft tissue infections). Daptomycin exerts its
      rapid bactericidal effect through insertion into and subsequent depolarisation of
      the bacterial cell membrane, a mode of action unlike that of any other available
      antibiotic. This novel mechanism of action makes the development of cross
      resistance between daptomycin and other antibiotic classes unlikely. Daptomycin
      is highly active in vitro against a range of Gram-positive pathogens, including
      both susceptible and multidrug-resistant staphylococci and enterococci.
      Bactericidal activity has also been demonstrated against both growing and
      stationary-phase organisms, suggesting potential utility in the treatment of deep
      seated infections. Two pivotal clinical studies comparing daptomycin 4 mg/kg per
      day intravenously with vancomycin or oxacillin-class antibiotics demonstrated the
      efficacy of daptomycin for treatment of cSSSIs. Daptomycin was well tolerated,
      with most adverse events considered to be unrelated to study medication, of mild
      to-moderate intensity, and with a frequency and distribution similar to those
      associated with comparator antibiotics. The favourable clinical profile and low
      potential for development of resistance combine to make daptomycin a promising
      alternative to current agents for treatment of Gram-positive bacterial
      infections.

PMID- 16445723
TI  - Quantitative evaluation of left ventricle performance from two dimensional echo
      images.
AB  - OBJECTIVES: We sought to quantify the left ventricle systolic dysfunction by a
      geometric index from two-dimensional (2D) echocardiography by implementing an
      automated fuzzy logic edge detection algorithm for the segmentation. BACKGROUND:
      The coronary injuries have repercussions on the left ventricle producing changes
      on wall contractility, the shape of the cavity, and as a whole changes on the
      ventricular function. METHODS: 2D echocardiogram and M-mode recordings were
      performed over the control group and those with the dysfunctions. From 2D
      recordings, individual frames were extracted for at least five cardiac cycles and
      then segmentation of left ventricle was done by automated fuzzy systems. In each
      frame, the volumes are measured and a geometric index, eccentricity ratio (ER),
      was derived. The endocardial fractional shortening (FS), midwall fractional
      shortening (mFS), and the relative wall thickness (RWT) were also measured in
      each case. RESULTS: Depressed value of endocardial FS (20.39 +/- 5.43 vs 34.28 +/
      9.36, P = 0.0046), mFS (33 +/- 8.3 vs 52.5 +/- 11.7, P = 0.0047), and the RWT
      (0.337 +/- 0.096 vs 0.525 +/- 0.119, P = 0.0002) was observed with dysfunction.
      ER measured at end-diastole (2.86 +/- 0.703 vs 4.14 +/- 0.38) and end-systole
      (3.14 +/- 0.79 vs 5.48 +/- 0.74) was found to be decreased in the dysfunction
      group and more significant at the end-systole (P = 0.00017 vs 6.6E-06).
      CONCLUSION: This work concludes that the regional and global left ventricle
      systolic dysfunction can be assessed by the ER measured at end-diastole and end
      systole from 2D echocardiogram and may contribute to the high rate of
      cardiovascular disorders.

PMID- 16445724
TI  - Using transthoracic two-dimensional echocardiography to guide the placement of
      coronary sinus catheters: a randomized study.
AB  - OBJECTIVE: To assess the value of transthoracic echocardiography (TTE) as an
      image guide in placing a coronary sinus catheter into the coronary sinus.
      METHODS: Sixty consecutive patients undergoing electrophysiologic study were
      randomized to TTE (30 patients, "TTE group") or x-ray fluoroscopy (30 patients,
      "x-ray group") as an image guide to assist in the placement of a coronary sinus
      catheter. RESULTS: The success rate of placing the coronary sinus catheter was
      96.7% in TTE group and 100% in x-ray group (P > 0.05). The procedure duration was
      5.8 +/- 5.7 minutes in TTE group and 5.9 +/- 3.3 minutes in x-ray group (P >
      0.05), The x-ray exposure time was 0.15 +/- 0 minute in TTE group and 4.2 +/- 2.8
      minutes in x-ray group (P < 0.0001). CONCLUSION: Using TTE as an image guide,
      coronary sinus cannulation is feasible and as rapid as standard x-ray
      fluoroscopy, without the radiation risk.

PMID- 16445725
TI  - Use of the ejection fraction-velocity ratio in the hemodynamic assessment of
      aortic bioprosthetic valves.
AB  - BACKGROUND: A new echocardiographic severity index of aortic valve stenosis has
      been recently introduced: the ejection fraction-velocity ratio (EFVR), which is a
      simple ratio ejection fraction/4Vmax2. This nonflow corrected index demonstrated
      an excellent accuracy in quantifying the effective orifice area (EOA) in native
      aortic valves. There is no information about the reliability of EFVR in assessing
      aortic EOA in patients with bioprostheses. METHODS: In 141 consecutive patients
      with aortic bioprostheses (85 males, mean age 74 +/- 9 years), EOA was calculated
      by both continuity equation (CE) and EFVR. RESULTS: The correlation between CE
      and EFVR was highly significant (r = 0.88; P < 0.0001). The area under the
      receiver operating characteristic (ROC) curve was 0.97 (considering a positive
      case CE < 1.0 cm2, best cutoff of EFVR was <1.06). Using CE as gold standard and
      a cutoff of 1.0 for both indexes, EFVR showed good sensitivity (80%) and
      specificity (98%). Also in a subgroup of 46 patients with moderate or severe
      mitral regurgitation, the EFVR had a good diagnostic accuracy (sensitivity 89%,
      specificity 97%). In 91 patients with ejection fraction < or = 50%, the EFVR
      confirmed good sensitivity (79%) and specificity (97%). CONCLUSIONS: The EFVR, a
      simple and not time-consuming index, demonstrated a good diagnostic accuracy in
      assessing EOA also in patients with aortic bioprostheses. The presence of
      moderate to severe mitral regurgitation or left ventricular dysfunction does not
      reduce significantly the reliability of this new index. The EFVR can be taken
      into consideration in the clinical practice, at least when CE measurements are
      technically difficult.

PMID- 16445726
TI  - Collagen fiber morphology determines echogenicity of myocardial scar:
      implications for image interpretation.
AB  - Fibrous tissue appears as echo dense areas on conventional ultrasound images;
      however, the determinants of such echo brightness have not been assessed. We
      demonstrated previously, using 600-MHz ultrasound images, that collagen fiber
      morphology determines echo brightness. In the current study, we tested the
      hypothesis that collagen fiber morphology also determines echogenicity of
      myocardial scar at the lower transducer frequencies used in conventional
      ultrasound. We examined both the infarcted and noninfarcted regions of rat hearts
      1 and 3 weeks after permanent coronary artery occlusion. Ultrasound images
      obtained from excised hearts were digitized to quantify echocardiographic
      brightness. The hearts were then sectioned, stained with picrosirius red, and
      examined with polarized light microscopy. We found that myocardial scar tissue
      appeared either hyperechoic or normoechoic depending on collagen fiber
      morphology. Specifically, the hyperechoic areas corresponded to the 3-week-old
      infarcted regions containing thick collagen fibers that appeared predominantly
      orange when viewed with polarized light. In contrast, normoechoic areas
      corresponded to the 1-week-old infarcted regions containing thin collagen fibers
      that appeared predominantly green and also to noninfarcted myocardium. We
      conclude that the echogenicity of tissue early after infarction is similar to
      that found in normal, noninfarcted myocardium, thus compromising the ability of
      echocardiography to distinguish between these two states based on echotexture.

PMID- 16445727
TI  - Stroke volume and mitral annular velocities: insights from uremic patients with
      significant valvular regurgitation.
AB  - OBJECTIVE: This study investigates the change in new diastolic indices in uremic
      patients who undergo regular hemodialysis (H/D). MATERIALS AND METHODS: We
      studied uremic patients receiving regular H/D. All patients were sinus rhythm
      before H/D. They had normal left ventricular systolic performance without
      regional wall motion abnormality. Patients were separated into two groups
      according to whether they had significant aortic or mitral regurgitation (AR or
      MR) or not. They received complete transthoracic echocardiographic examinations.
      Stroke volume (SV) was calculated as the product of the time-velocity integral
      (TVI) and cross-sectional area of aortic annulus. Flow propagation velocity (FPV)
      was measured by color M-mode echocardiography in apical four-chamber view. Mitral
      annulus tissue Doppler velocities--peak systolic (Sa), early diastolic, and late
      diastolic--were measured from septal and lateral wall. All these parameters were
      obtained immediately before and after H/D. Paired data were compared. RESULT: H/D
      amount was strongly correlated with the change of SV. After H/D, the reduction of
      SV in patients without AR or MR (control group) was obvious but it was not
      significant in patients with significant AR or MR (study group). There were
      significant differences in mitral inflow velocities, FPV, and mitral annular
      velocities (except septal Sa) in the control group. In the study group,
      predialytic and postdialytic parameters of new diastolic indexes had no
      statistical difference. CONCLUSION: New echocardiographic indexes of uremic
      patients with significant AR or MR were relatively preload-independent. The
      phenomenon was possibly related to insignificant change of SV after H/D.

PMID- 16445728
TI  - Tissue Doppler echocardiography reveals insufficient contractile reserve
      recruitment during effort in subjects with mitral valve prolapse and those with
      thick mitral valve.
AB  - OBJECTIVE: To assess by tissue Doppler echocardiography (TDE), the tissue
      velocities, both at rest and after exercise stress testing, in subjects with
      mitral valve prolapse (MVP) and those with thick mitral valve (TMV). METHODS:
      Twenty individuals with typical MVP, 30 with TMV, and 30 healthy controls were
      enrolled. TDE was performed at the basal-inferior wall and the parameters
      evaluated were the S, Em, and Am velocities, as well as the Em/Am ratio. RESULTS:
      The mean S-wave at rest was higher in subjects with MVP compared to that of the
      TMV (P < 0.01) and the control groups (P = 0.00005), whereas after exercise it
      was higher in the control group compared to either MVP (P = 0.013) or TMV group
      (P = 0.00002). The mean Em wave at rest was higher in the control individuals
      both at rest (P = 0.007 compared with MVP group and P = 0.013 compared with TMV
      group), and after exercise (P = 0.0002 and 0.0009, respectively). The Am wave in
      the MVP group was higher compared with TMV and control subjects at rest (P =
      0.022 and 0.00001, respectively) but it was not after exercise (P = ns for both
      comparisons). The Em/Am ratio of the control group at rest was higher than that
      of the MVP (P = 0.0000) and TMV (P = 0.00028) groups. However, after exercise, it
      was higher only when compared with the MVP group (P = 0.016). CONCLUSIONS:
      Subjects with MVP and those with TMV exhibit a less effective contractile
      response to exercise compared to healthy individuals. Some degree of diastolic
      dysfunction, particularly after exercise, was also detected in the individuals
      with MVP.

PMID- 16445729
TI  - Tissue Doppler evaluation of intraventricular asynchrony in isolated left bundle
      branch block.
AB  - BACKGROUND: The aim of this study was to evaluate normal subjects with isolated
      left bundle branch block (LBBB) using tissue Doppler imaging (TDI) for the
      presence of intraventricular asynchrony. METHODS AND RESULTS: For this purpose,
      23 subjects with isolated LBBB were compared with age-matched asymptomatic
      healthy subjects without LBBB with respect to global ejection fraction (EF) and
      isovolumic contraction time (ICTm) in separate left ventricular segments. TDI
      evaluation revealed prolongation of the ICTm in all of the segments in the LBBB
      group. Moreover, the ICTm differed significantly in each segment in the LBBB
      group. The ICTm in the lateral segments were shown to be longer compared to the
      anteroseptal segments. CONCLUSION: Our results indicate the presence of
      intraventricular asynchrony in isolated LBBB. This fact may play a role in the
      decreased global EF and increased cardiac mortality in patients with isolated
      LBBB.

PMID- 16445730
TI  - Assessment of left atrial appendage by live three-dimensional echocardiography:
      early experience and comparison with transesophageal echocardiography.
AB  - BACKGROUND: Live Three-Dimensional Echocardiography (L3D, Sonos 7500, Philips)
      has the potential to visualize all cardiac structures including left atrial
      appendage (LAA). We tested the feasibility of evaluating LAA by L3D and compared
      the findings to transthoracic echocardiography (2D) and in a subset of patients
      with transesophageal echocardiography (TEE). METHODS: L3D images were obtained in
      204 consecutive patients referred for routine 2D or TEE. We performed wide-angled
      acquisitions from parasternal and apical views. TomTec system (4D Cardio-view, RT
      1.2) was used to visualize LAA from multiple vantage points. RESULTS: LAA was
      adequately visualized by L3D in 139 of 204 (68.1%) patients. L3D visualization
      was dependent on image quality, suboptimal in 100 and diagnostic in 104 patients.
      Overall, LAA was visualized in 93 (45.5%) patients by 2D compared to 139 (68.1%)
      by L3D (P < 0.0001). In 100 patients with suboptimal image quality by L3D, LAA
      visualization was 16% by 2D and 35% by L3D, whereas in 104 patients with
      diagnostic images, LAA was visualized in 77 (74%) by 2D and in all 104 (100%)
      patients by L3D (P < 0.0001). In 37 patients referred for transesophageal
      echocardiography (TEE), live three-dimensional echocardiography (L3D) visualized
      left atrial appendage (LAA) in 34 patients with diagnostic image quality. Eight
      patients with LAA thrombi on TEE had thrombi detected by L3D as well. All
      patients with LAA thrombus had enlarged LA by both 2D and TEE. CONCLUSIONS: L3D
      is a promising technique in evaluation of LAA with and without thrombi. In
      patients with good quality transthoracic images L3D may be used as a screening
      tool in assessment of LAA.

PMID- 16445731
TI  - Nonatherosclerotic ostial stenosis of left main coronary artery:
      echocardiographic assessment and follow-up after surgical treatment.

PMID- 16445732
TI  - Unusual pulmonary venous flow profile in a patient with mitral valve perforation
      secondary to bacterial endocarditis.
AB  - Pulmonary venous flow patterns have been well described in the literature to
      assess severity of mitral regurgitation (MR) and the degree of diastolic
      dysfunction. We report a case of posterior mitral leaflet perforation due to
      bacterial endocarditis causing an alteration of pulmonary venous flow, not
      previously described in the literature. This pulmonary venous flow pattern is
      unique in that it reflects dynamic changes in left atrial pressure in the
      background of severe MR.

PMID- 16445733
TI  - Echocardiographic diagnosis of a case with giant right atrial aneurysm.
AB  - Right atrial aneurysm (RAA) is a very rare anomaly. Rarer still is its
      association with atrial septal defect (ASD). We reported a case of a 42-year-old
      woman with giant RRA and secundum type ASD detected by means of transthoracic
      echocardiography.

PMID- 16445734
TI  - Continuous murmur due to a mediastinal tumor.
AB  - Despite the lengthy differential diagnosis of causes of cardiac murmurs, the
      association of a mediastinal mass and a continuous murmur is very rare. We report
      herein a case of a mediastinal tumor and continuous murmur where transthoracic
      echocardiography provided clear differential diagnosis and demonstrated the cause
      of murmur.

PMID- 16445735
TI  - Primary cardiac non-Hodgkin's lymphoma diagnosed by transthoracic
      echocardiography.
AB  - Primary cardiac lymphomas are extremely rare and can be diagnosed by
      echocardiography. We present the case of a 79-year-old man with an intracardiac
      mass, shown to be an aggressive large B-cell lymphoma by mediastinal aspiration,
      who had rapid regression of the tumor following one cycle of chemotherapy.

PMID- 16445736
TI  - The usefulness of Doppler myocardial imaging in the study of the athlete's heart
      and in the differential diagnosis between physiological and pathological
      ventricular hypertrophy.
AB  - Athlete's heart is a cardiac adaptation to long-term, intensive training, which
      includes changes as increased ventricular cavity diameters, wall thickness and
      mass, produced with a degree consistent with sports activities and exercise
      programs. The Doppler myocardial imaging (DMI) permits characterization of the
      velocities of each ventricular myocardial segment by placing the sample volume at
      the center of the cardiac muscle. Even if the standard two-dimensional (2D)
      echocardiography represents an irreplaceable method in the evaluation of cardiac
      adaptations to physical exercise, the data currently available suggests the
      usefulness of DMI in the assessment of the myocardial systolic and diastolic
      functions of the athlete's heart. In particular, an athlete's left ventricular
      hypertrophy is characterized by a "supernormal" DMI pattern, with increased
      myocardial early-diastolic velocity. Therefore, DMI analysis in the trained
      subject has demonstrated interesting prospective for: (1) the differential
      diagnosis from pathological, both, left and right ventricular hypertrophy; (2)
      the prediction of cardiac performance during physical effort; (3) the evaluation
      of the biventricular interaction; (4) the analysis of the myocardial adaptations
      to various training protocols; and (5) the early identification of specific
      genotypes associated with cardiomyopathies. On this ground, a combined use of
      standard 2D echo and DMI may be taken into account for a valid noninvasive and
      easy-repeatable evaluation of both physiological and pathological ventricular
      hypertrophies.

PMID- 16445737
TI  - Definitive diagnosis of descending thoracic aortic dissection by real time/live
      three-dimensional transthoracic echocardiography.
AB  - We describe a patient with descending thoracic aortic dissection in whom three-
      dimensional transthoracic echocardiography was able to clearly visualize the
      dissection flap en face as a sheet of tissue, as well as demonstrate a large
      communication between the true and false lumen in three dimensions, enabling a
      definitive diagnosis of dissection.

PMID- 16445738
TI  - Transthoracic echocardiographic visualization of a right coronary to left
      anterior descending artery collateral.

PMID- 16445739
TI  - Fungal ball blocking the aortic valve.

PMID- 16445740
TI  - Trepopnea in a patient with cardiac tumor.

PMID- 16445741
TI  - Dynamic systolic left ventricular gradients: differential diagnosis and
      management.

PMID- 16445742
TI  - Atrial stunning masquerading as restrictive Doppler flow pattern: a case of
      mitral inflow "pseudorestriction".

PMID- 16445743
TI  - Extracellular and cellular mechanisms sustaining metal tolerance in
      ectomycorrhizal fungi.
AB  - This review focuses on recent evidence that identifies potential extracellular
      and cellular mechanisms that may be involved in the tolerance of ectomycorrhizal
      fungi to excess metals in their environment. It appears likely that mechanisms
      described in the nonmycorrhizal fungal species are used in the ectomycorrhizal
      fungi as well. These include mechanisms that reduce uptake of metals into the
      cytosol by extracellular chelation through extruded ligands and binding onto cell
      wall components. Intracellular chelation of metals in the cytosol by a range of
      ligands (glutathione, metallothioneins), or increased efflux from the cytosol out
      of the cell or into sequestering compartments are also key mechanisms conferring
      tolerance. Free-radical scavenging capacities through the activity of superoxide
      dismutase or production of glutathione add another line of defence against the
      toxic effect of metals.

PMID- 16445744
TI  - Homology effects in Neurospora crassa.
AB  - It has become clear in the past few years that eukaryotic organisms possess
      different genetic systems to counter viruses, transposons and other repeated
      elements such as transgenes that could otherwise accumulate in the genome. In
      addition to serving as a model organism for genetic, biochemical and molecular
      studies, Neurospora crassa has proved to be a paradigm for the study of gene
      silencing mechanisms. Indeed, its genome can be protected from expansion of
      selfish nucleic acids by a variety of mechanisms that inactivate duplicated
      sequences. Studies of these mechanisms have made a fundamental contribution to
      the understanding of the gene-silencing field.

PMID- 16445746
TI  - Pathfinders and trailblazers: a prokaryotic targeting system for transport of
      folded proteins.
AB  - The twin-arginine (Tat) protein translocase is a highly unusual protein transport
      machine that is dedicated to the movement of folded proteins across the bacterial
      cytoplasmic membrane. Proteins are targeted to the Tat pathway by means of N
      terminal signal peptides harbouring a distinctive twin-arginine motif. In this
      minireview, we describe our current knowledge of the Tat system, paying
      particular attention to the function of the TatA protein and to the often
      overlooked step of signal peptide cleavage.

PMID- 16445745
TI  - Re-examining the role and random nature of phase variation.
AB  - Phase variation in bacteria is often considered a random process that has evolved
      to facilitate immune evasion in a host. Here, alternative biological roles for
      this process are presented and discussed, incorporating recent studies on
      nonpathogenic and commensal bacterial species. Furthermore, the integration of
      phase variation into bacterial regulatory networks and the relevance of this for
      considering phase variation as a random process are reviewed. Novel approaches
      are needed to study phase variation and its biological roles, but the insights
      obtained can contribute significantly to our understanding of the dynamic
      behaviour of bacterial populations and their interactions with the environment.

PMID- 16445747
TI  - Promoters and their regulation in Ustilago maydis and other phytopathogenic
      fungi.
AB  - The lifestyle of phytopathogenic fungi is strongly determined by their
      environment. This implies that mechanisms providing for versatile gene regulation
      in response to external signals or during host associations exist. In Ustilago
      maydis, central players of pathogenic development are the high mobility group box
      protein Prf1 that binds to the pheromone response element and the homeodomain
      transcription factor b, which recognizes an hsg-like consensus motif known from
      yeast Mata1-Matalpha2 DNA binding. Transcription of prf1 is influenced by
      multiple inputs and this is reflected by its modular promoter structure. Analysis
      of the U. maydis mig promoters provides a link to transcriptional regulation
      during biotrophic growth. Furthermore, recognition of repeated GATA sequences as
      well as of triplet motifs by transcription factors with binuclear Zn(II)(2)Cys(6)
      DNA-binding domains appears to mediate diverse transcriptional responses relevant
      for phytopathogenic fungi. Although present studies shed some light on the
      complexity of transcriptional processes operating in phytopathogenic fungi,
      further investigation of promoter structures including the involvement of
      ubiquitous promoter elements is needed. Confronted with increasing genome-wide
      analysis, knowledge of promoter structures not only allows predicting
      transcriptional regulation, but might also advance our understanding of
      transcriptional networks.

PMID- 16445748
TI  - Analysis of antibiotic resistance gene expression in Pseudomonas aeruginosa by
      quantitative real-time-PCR.
AB  - In Pseudomonas aeruginosa many of the clinically relevant resistance mechanisms
      result from changes in gene expression as exemplified by the Mex drug efflux
      pumps, the AmpC beta-lactamase and the carbapenem-specific porin OprD. We used
      quantitative real-time-PCR to analyze the expression of these genes in
      susceptible and antibiotic-resistant laboratory and clinical strains. In nalB
      mutants, which overexpress OprM, we observed a four- to eightfold increase in the
      expression of mexA, mexB, and oprM genes. MexX and mexY genes were induced eight
      to 12 times in the presence of 2 mg L(-1) tetracycline. The mexC/oprJ and
      mexE/oprN gene expression levels were increased 30- to 250-fold and 100- to 760
      fold in nfxB and nfxC mutants, respectively. We further found that in defined
      laboratory strains expression levels of ampC and oprD genes paralleled beta
      lactamase activity and OprD protein levels, respectively. Our data support the
      use of quantitative real-time-PCR chain reaction for the analysis of the
      antimicrobial resistance gene expression in P. aeruginosa.

PMID- 16445749
TI  - Food commensal microbes as a potentially important avenue in transmitting
      antibiotic resistance genes.
AB  - The rapid emergence of antibiotic-resistant (ART) pathogens is a major threat to
      public health. While the surfacing of ART food-borne pathogens is alarming, the
      magnitude of the antibiotic resistance (AR) gene pool in food-borne commensal
      microbes is yet to be revealed. Incidence of ART commensals in selected retail
      food products was examined in this study. The presence of 10(2)-10(7) CFU of ART
      bacteria per gram of foods in many samples, particularly in ready-to-eat,
      'healthy' food items, indicates that the ART bacteria are abundant in the food
      chain. AR-encoding genes were detected in ART isolates, and Streptococcus
      thermophilus was found to be a major host for AR genes in cheese microbiota.
      Lactococcus lactis and Leuconostoc sp. isolates were also found carrying AR
      genes. The data indicate that food could be an important avenue for ART bacterial
      evolution and dissemination. AR-encoding plasmids from several food-borne
      commensals were transmitted to Streptococcus mutans via natural gene
      transformation under laboratory conditions, suggesting the possible transfer of
      AR genes from food commensals to human residential bacteria via horizontal gene
      transfer.

PMID- 16445750
TI  - Identification of Mycobacterium species by comparative analysis of the dnaA gene.
AB  - For the establishment of a diagnostic tool for mycobacterial species, a part of
      the dnaA gene was amplified and sequenced from clinically relevant 27
      mycobacterial species as well as 49 clinical isolates. Sequence variability in
      the amplified segment of the dnaA gene allowed the differentiation of all species
      except for Mycobacterium tuberculosis, Mycobacterium africanum and Mycobacterium
      microti, which had identical sequences. Partial sequences of dnaA from clinical
      isolates belonging to three frequently isolated species revealed a very high
      intraspecies similarity, with a range of 96.0-100%. Based on the dnaA sequences,
      a species-specific primer set for Mycobacterium kansasii and Mycobacterium gastri
      was successfully designed for a simple loop-mediated isothermal amplification
      method. These results demonstrate that the variable sequences in the dnaA gene
      were species specific and were sufficient for the development of an accurate and
      rapid diagnosis of Mycobacterium species.

PMID- 16445751
TI  - Light accelerates the splicing of srh1 homologue gene transcripts in aerial
      mycelia of Trichoderma viride.
AB  - The expression of the Tvsrh1 gene encoding conidial hydrophobin was investigated
      during the development of surface-cultivated Trichoderma viride mycelia under
      different illumination regimes. Three transcripts of the whole gene amplified
      from the total mRNA were found with lengths of 400, 323 and 272 bp. The 400-bp
      transcript was slowly converted to the shorter forms in the dark. Light-pulse
      dramatically increased the rate of conversion, and a permanent illumination of
      mycelia was most efficient in this process. The sequencing of transcripts
      revealed that the 400 bp transcript contains two introns, whereas the
      intermediate one contains only one intron located distally from the 5'-end. The
      shortest transcript was without introns. The sum of all transcripts remained
      almost unchanged in the dark and increased upon the light pulse but decreased
      during development under permanent illumination. The appearance of conidia
      coincided with the complete conversion of the transcripts. The results showed
      that the splicing of the two introns was not random but sequential, and that it
      did not follow the cotranscriptional mechanism. Furthermore, they suggested that
      mRNA processing could represent another regulation level of gene expression by
      light during the photo-induced conidiation in T. viride.

PMID- 16445752
TI  - sucAB and sucCD are mutually essential genes in Escherichia coli.
AB  - sucAB and sucCD of Escherichia coli encode enzymes that generate succinyl-CoA
      from 2-oxoglutarate and succinate, respectively. Their mutual essentiality was
      studied. sucAB and sucCD could be deleted individually, but not simultaneously.
      The mutual essentiality of sucAB and sucCD was further confirmed by the
      conditional expression of sucABCD, sucAB, and sucCD under the control of a P(BAD)
      in E. coli MG1655, E. coli MG1655 (DeltasucCD), and E. coli MG1655 (DeltasucAB),
      respectively. These strains grew well in Luria-Bertani medium containing 0.1%
      arabinose, but not in the absence of arabinose unless the medium was supplemented
      with succinyl-CoA. Our results indicate that either sucAB or sucCD is enough to
      produce succinyl-CoA that is essential for cell viability.

PMID- 16445753
TI  - Detection of Tuber melanosporum DNA in soil.
AB  - Our objectives were (i) to develop a molecular method to detect mycelia of Tuber
      melanosporum (black truffle) in soil and (ii) to test for mycelial distribution
      around two truffle-bearing Quercus ilex trees in a truffle orchard. Isolation of
      total DNA from soil was performed, followed by PCR amplification with T.
      melanosporum-specific primers and restriction analysis. To address the detection
      sensitivity level, soil samples were inoculated with known amounts of gleba of T.
      melanosporum. The detection limit was >/=11.4 mug of hyphae g(-1) of soil.
      Mycelium was detected primarily within the area defined by the truffle burn and
      within the top 35 cm of the soil in all directions from the trees.

PMID- 16445754
TI  - The bacterium Paenibacillus validus stimulates growth of the arbuscular
      mycorrhizal fungus Glomus intraradices up to the formation of fertile spores.
AB  - Two isolates of Paenibacillus validus (DSM ID617 and ID618) stimulated growth of
      the arbuscular mycorrhizal fungus Glomus intraradices Sy167 up to the formation
      of fertile spores, which recolonize carrot roots. Thus, the fungus was capable of
      completing its life cycle in the absence of plant roots, but relied instead on
      the simultaneous growth of bacteria. The supernatant of a mixed batch culture of
      the two P. validus isolates contained raffinose and another, unidentified
      trisaccharide. Among the oligosaccharides tested, raffinose was most effective in
      stimulating hyphal mass formation on plates but could not promote growth to
      produce fertile spores. A suppressive subtractive hybridization library followed
      by reverse Northern analyses indicated that several genes with products involved
      in signal transduction are differentially expressed in G. intraradices SY 167
      when grown in coculture with P. validus (DSM 3037). The present investigation,
      while likely representing a significant step forward in understanding the
      arbuscular mycorrhizal fungus symbioses, also confirms that its optimal
      establishing and functioning might rely on many, as yet unidentified factors.

PMID- 16445755
TI  - Establishment of a genotyping scheme for Coxiella burnetii.
AB  - Coxiella burnetii is the causative agent of Q fever. The bacterium is highly
      infectious and is classified as a category B biological weapon. The tools of
      molecular biology are of utmost importance in a rapid and unambiguous
      identification of C. burnetii in naturally occurring Q fever outbreaks, or in
      cases of a deliberate release of the infectious agent. In this work, development
      of a multiple locus variable number tandem repeats (VNTR) analysis (MLVA) for the
      characterization of C. burnetii is described. Sixteen C. burnetii isolates and
      five passage history/laboratory variants were characterized. The VNTR markers
      revealed many polymorphisms resulting in nine unique MLVA types that cluster into
      five different clusters. This proves that the MLVA system is highly
      discriminatory. The selected VNTR markers were stable. The MLVA method developed
      in this report is a promising tool for the characterization of C. burnetii
      isolates and their epidemiological study.

PMID- 16445756
TI  - Deinococcus mumbaiensis sp. nov., a radiation-resistant pleomorphic bacterium
      isolated from Mumbai, India.
AB  - A radiation-resistant, Gram-negative and pleomorphic bacterium (CON-1) was
      isolated from a contaminated tryptone glucose yeast extract agar plate in the
      laboratory. It was red pigmented, nonmotile, nonsporulating, and aerobic, and
      contained MK-8 as respiratory quinone. The cell wall of this bacterium contained
      ornithine. The major fatty acids were C16:0, C16:1, C17:0, C18:1 and iso C18:0.
      The DNA of CON-1 had a G+C content of 70 mol%. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that CON-1 exhibited a maximum similarity (94.72%)
      with Deinococcus grandis. Based on the genotypic, phenotypic and chemotaxonomic
      characteristics, the bacterium CON-1 was identified as a new species of the genus
      Deinococcus, for which the name Deinococcus mumbaiensis sp. nov. is proposed. The
      type strain of D. mumbaiensis is CON-1 (MTCC 7297(T)=DSM 17424(T)).

PMID- 16445757
TI  - The widespread occurrence of the enterohemolysin gene ehlyA among environmental
      strains of Escherichia coli.
AB  - The putative virulence factor enterohemolysin, encoded by the ehlyA gene, has
      been closely associated with the pathogenic enterohemorrhagic Escherichia coli
      (EHEC) group. Escherichia coli isolates from effluents from seven geographically
      dispersed municipal wastewater treatment plants were screened for the presence of
      enterohemolysin. A total of 338 E. coli isolates were found to express the ehlyA
      gene. However, none of the isolates contained the toxin-encoding genes (stxA or
      stxB) associated with EHEC. Two of the 338 isolates possessed the virulence
      factor intimin, encoded by the eae gene. These findings suggest that the ehlyA
      gene may be widely distributed among non-EHEC isolates in the environment.

PMID- 16445758
TI  - Characterization of the chromosomal class A beta-lactamase CKO from Citrobacter
      koseri.
AB  - The gene bla(CKO) encoding the chromosomal class A beta-lactamase of Citrobacter
      koseri was cloned and sequenced. CKO was found to display only 41% identity with
      SED-1 from Citrobacter sedlakii and 36% with CdiA from Citrobacter amalonaticus
      (formerly Citrobacter diversus). No transcriptional regulator was found upstream
      from bla(CKO). Silent and missense mutations were detected in four bla(CKO) genes
      amplified from different C. koseri clinical isolates, but the CKO variants
      displayed identical biochemical behaviours. A bla(CKO)-specific polymerase chain
      reaction confirmed that bla(CKO) is present only in C. koseri and therefore
      represents an interesting tool with which to differentiate C. koseri from the
      other Citrobacter spp.

PMID- 16445759
TI  - Interaction analysis of the AAA ATPase TAA43 by the bacterial two-hybrid system.
AB  - The TAA43 ATPase of Thermoplasma acidophilum, an archaeal member of the AAA
      protein family, is known to have an atypical oligomeric state and a nonspecific
      association with high-molecular-weight protein complexes. We assessed the in vivo
      binding pattern of TAA43 using the bacterial two-hybrid system. We found 36
      positive isolates interacting with TAA43. Our analysis showed that TAA43
      interacts preferentially with nonribosomal proteins containing ribosomal domains
      and regions involved in RNA metabolism.

PMID- 16445760
TI  - Allelic exchange and site-directed mutagenesis probe the contribution of ActA
      amino-acid variability to phosphorylation and virulence-associated phenotypes
      among Listeria monocytogenes strains.
AB  - To test the hypothesis that actA allelic variation contributes to virulence
      differences among Listeria monocytogenes strains, cell-to-cell spread and
      intracellular ActA phosphorylation patterns were characterized for 14 wild-type
      isolates and selected isogenic mutants. Our data show that (i) while actA allelic
      variation is not responsible for enhanced cell-to-cell spread observed in
      epidemic clone I strains, actA allelic variation may contribute to reduced plaque
      size observed in some isolates, (ii) actA sequence alone determines
      phosphorylation-dependent ActA banding patterns, and (iii) sequence variation at
      the positively selected ActA residue 498 does not contribute to ActA
      phosphorylation patterns or to differences in cell-to-cell spread.

PMID- 16445761
TI  - Novel architecture of family-9 glycoside hydrolases identified in cellulosomal
      enzymes of Acetivibrio cellulolyticus and Clostridium thermocellum.
AB  - We have sequenced a new gene, cel9B, encoding a family-9 cellulase from a
      cellulosome-producing bacterium, Acetivibrio cellulolyticus. The gene includes a
      signal peptide, a family-9 glycoside hydrolases (GH9) catalytic module, two
      family-3 carbohydrate-binding modules (CBM3c-CBM3b tandem dyad) and a C-terminal
      dockerin module. An identical modular arrangement exists in two putative GH9
      genes from the draft sequence of the Clostridium thermocellum genome. The three
      homologous CBM3b modules from A. cellulolyticus and C. thermocellum were
      overexpressed, but, surprisingly, none bound cellulosic substrates. The results
      raise fundamental questions concerning the possible role(s) of the newly
      described CBMs. Phylogenetic analysis and preliminary site-directed mutagenesis
      studies suggest that the catalytic module and the CBM3 dyad are distinctive in
      their sequences and are proposed to constitute a new GH9 architectural theme.

PMID- 16445762
TI  - A new species of Pythium with ornamented oogonia: morphology, taxonomy, internal
      transcribed spacer region of its ribosomal RNA, and its comparison with related
      species.
AB  - Pythium spiculum sp. nov. was isolated from soil samples taken in a vineyard in
      the Burgundian region of France and from different locations in Spain and
      Portugal. The oomycete has spiny oogonia and does not sporulate readily. It
      resembles Pythium mamillatum Meurs, but has its own distinguishing
      characteristics. It also exhibits sickle-shaped as well as spherical appressoria
      which at times are associated with sex organs like those found in Pythium
      abappressorium Paulitz and Pythium contiguanum Paul. Sequencing of the internal
      transcribed spacer region of its nuclear ribosomal DNA and a close look at its
      morphological characters have now enabled us to describe it as a new species. The
      internal transcribed spacer region of its rRNA gene sequence is comprised of 945
      bases. This oomycete is closely related to the members that form ornamented or
      spiny oogonia like Pythiummamillatum, Pythium spinosum and Pythium irregulare but
      also with those producing smooth-walled oogonia like Pythium paroecandrum,
      Pythium sylvaticum and Pythium cylindrosporum. Taxonomic description of this new
      species, its comparison with related oomycetes, the sequence of the internal
      transcribed spacer region of its rRNA gene and the phylogenetic tree, are given
      here.

PMID- 16445763
TI  - Acid phosphatase production by Aspergillus niger N402A in continuous flow
      culture.
AB  - The production of acid phosphatases (E.C.3.1.3.2, ACPs) by Aspergillus niger
      N402A is regulated by specific growth rate, as well as phosphate availability and
      pH, as demonstrated by studies in continuous flow culture. Specific ACP activity
      was highest when A. niger was grown at pH 6.3 (64+/-8 U g(-1)) or pH 2.8 (99+/-11
      U g(-1)), at a dilution rate of 0.07 h(-1) and phosphate concentrations below
      0.46 mM. ACP production was growth correlated for specific growth rates between
      0.07 and 0.13 h(-1). Four different ACPs, including two phytases, were produced
      by A. niger N402A. The ACP and the phytase with maximal activities at pH 5.5 were
      differentially expressed at different culture pH values, with greater production
      at low pH.

PMID- 16445766
TI  - Reduction of immunosuppression for transplant-associated skin cancer: expert
      consensus survey.
AB  - BACKGROUND: Reduction of immunosuppression is considered a reasonable adjuvant
      therapeutic strategy in solid-organ transplant recipients experiencing multiple
      or high-risk skin cancers. However, the literature provides no guidance about
      what threshold of cancer development would warrant initiation of reduction of
      immunosuppression. OBJECTIVES: To develop expert consensus guidelines for
      initiation of reduction of transplant-associated immunosuppression for solid
      organ transplant recipients with severe skin cancer. METHODS: An expert consensus
      panel was convened by the International Transplant Skin Cancer Collaborative and
      Skin Care for Organ Transplant Patients Europe Reduction of Immunosuppression
      Task Force. Thirteen hypothetical patient scenarios with graduated morbidity and
      mortality risks were presented and mean and mode expert opinions about
      appropriate level of reduction of systemic immunosuppression (mild, moderate,
      severe) were generated. RESULTS: Mild reduction of transplant-associated
      immunosuppression was considered warranted once multiple skin cancers per year
      developed or with individual high-risk skin cancers. Moderate reduction was
      considered appropriate when patients experienced > 25 skin cancers per year or
      for skin cancers with a 10% 3-year risk of mortality. Severe reduction was
      considered warranted only for life-threatening skin cancers. CONCLUSIONS:
      Reduction of immunosuppression is considered a reasonable adjuvant management
      strategy for transplant recipients with numerous or life-threatening skin
      cancers. Proposed guidelines are presented for the graduated reduction of
      immunosuppression coincident with the increasing skin cancer risks.

PMID- 16445767
TI  - Investigation of keratinocyte regulation of collagen I synthesis by dermal
      fibroblasts in a simple in vitro model.
AB  - BACKGROUND: Hypertrophic scarring and skin graft contracture are major causes of
      morbidity after burn injuries. A prominent feature is excessive fibroplasia with
      accumulation of increased fibrillar collagen relative to normal scar tissue. The
      application of split-thickness skin grafts or cultured epithelial autografts to
      burn wounds is known to reduce scarring and contraction. OBJECTIVES: To
      investigate further how the keratinocyte influences underlying fibroblast
      behaviour by examining the influence of keratinocytes on fibroblast collagen
      synthesis, using a new assay for collagen synthesis never previously applied to
      skin cell biology. METHODS: We investigated the influence of the keratinocyte on
      fibroblast synthesis of type I collagen using an immunoassay for the
      aminoterminal propeptide of type I collagen (P1NP) in conditioned medium from
      monocultures and cocultures of keratinocytes and fibroblasts over 14 days. The
      importance of the physical presence of the keratinocyte was investigated by
      comparing cocultures of keratinocytes and fibroblasts against fibroblast
      monocultures with keratinocyte-conditioned medium. Pharmacological agents known
      to promote fibroblast proliferation [basic fibroblast growth factor (bFGF)],
      keratinocyte proliferation [insulin-like growth factor (IGF)-1], modify scarring
      in vivo[tumour necrosis factor (TNF)-alpha] or modify collagen biochemistry
      [putrescine, estrone, estradiol and beta-aminopropionitrile (beta-APN)] were then
      investigated for their effect on collagen synthesis in fibroblasts and in
      keratinocyte/fibroblast cocultures. RESULTS: Keratinocytes in coculture with
      fibroblasts, and keratinocyte-conditioned medium, both reduced fibroblast P1NP
      synthesis. Of the pharmacological agents investigated, bFGF, IGF-1, TNF-alpha and
      beta-APN all increased collagen synthesis both in monocultures of fibroblasts and
      in cocultures of keratinocytes and fibroblasts. CONCLUSIONS: Fibroblast collagen
      synthesis appears to be downregulated by keratinocyte-derived cytokines.
      Fibroblast growth factors and proinflammatory cytokines appear to be able
      partially to overcome this downregulation and to increase collagen synthesis.

PMID- 16445768
TI  - Tob is a potential marker gene for the basal layer of the epidermis and is stably
      expressed in human primary keratinocytes.
AB  - BACKGROUND: Epidermis consists of multiple layers, from the proliferating basal
      layer to terminal differentiated cornified layers, and these layers are defined
      by differentiation status. Tob gene product is known to be a member of the BTG
      antiproliferative protein family. We investigated the expression pattern of Tob
      gene product to understand the possible role in differentiation of keratinocytes
      and epidermis. OBJECTIVES: In this study, we examined the expression of Tob gene
      product in the primary cultured human keratinocytes and in the in vivo epidermis.
      METHODS: The expression of Tob gene product was assessed by Western blotting
      analysis. Cellular localization of Tob was detected using the green fluorescent
      protein-tagged Tob cDNA expression construct. In vivo expression of Tob gene
      product in the epidermis was determined by immunohistochemistry with paraffin
      sections. RESULTS: Tob family members are degraded by the ubiquitine-proteasome
      system triggered by the growth signal. Tob is stably and abundantly expressed in
      primary cultured human keratinocytes. Furthermore, the expression of Tob in the
      keratinocytes persists during the differentiation induced by calcium; however, it
      was not detected in primary cultured fibroblasts. Also, the subcellular
      localization of Tob is mainly in the cellular membrane in the primary human
      keratinocytes. We evaluated Tob expression in normal skin, oral mucosa and
      different diseases, such as psoriasis, X-linked ichthyosis and squamous cell
      carcinoma (SCC). Using immunohistochemical analysis, we observed that Tob was
      selectively expressed in the basal layer of X-linked ichythyosis and the
      hyperproliferative basal layer of psoriasis and oral mucosa as well as in normal
      epidermis. In SCC, the expression of Tob gene product was relatively decreased.
      CONCLUSIONS: Tob is stably expressed in primary human keratinocytes and it is
      specifically expressed in the basal layer of in vivo epidermis.

PMID- 16445769
TI  - Possible role of Fas/Fas ligand-mediated apoptosis in the pathogenesis of fixed
      drug eruption.
AB  - BACKGROUND: Although epidermal and dermal T cells play roles in the pathogenesis
      of fixed drug eruption (FDE), not much is known about keratinocyte death and its
      precise mechanism in FDE. OBJECTIVES: Our aim is to elucidate the mechanism that
      underlies keratinocyte death in FDE, that is, the role of apoptosis and its
      signalling pathway. METHODS: We first examined the involvement of apoptosis in
      the active FDE lesions by terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labelling (TUNEL) assay and
      immunohistochemical analysis of caspase-3. We then examined the expressions of
      Fas and Fas ligand (FasL) to deduce the possible upstream signalling pathway of
      apoptosis, if apoptosis were involved. We finally characterized the infiltrated T
      cell subpopulations in the active FDE lesions. RESULTS: In the active FDE
      lesions, TUNEL positivity was strongly observed in the basal keratinocytes, and
      also weakly observed in the upper dermal infiltrates as well as in a few
      keratinocytes in the granular layer. The distribution of TUNEL-positive cells was
      similar to that of the strong staining of active capase-3. Fas was found mainly
      in the keratinocytes and some infiltrated dermal cells, whereas FasL was
      identified predominantly in the intraepidermal and dermal infiltrated cells and
      in some basal keratinocytes. Overlapping expression of Fas and FasL was
      accompanied by apoptosis in the FDE lesions. Many of the infiltrated mononuclear
      cells were CD8+. Perforin was rarely observed in the FDE lesions. CONCLUSIONS:
      These findings suggest that apoptosis of the keratinocyte is highly likely to be
      involved in the pathogenesis of FDE, and this cytotoxicity might be predominantly
      mediated by the FasL of the infiltrating CD8+ T cells, possibly also playing an
      inflammatory role.

PMID- 16445770
TI  - A method to induce stable atopic dermatitis-like symptoms in NC/Nga mice housed
      with skin-lesioned mice.
AB  - BACKGROUND: Itching is a characteristic symptom in various forms of dermatosis,
      especially atopic dermatitis; consequently it is a major diagnostic criterion.
      All features are similar to events seen in patients, hence NC/Nga mice are
      considered to be a suitable model of human atopic dermatitis. However, there were
      data spreads in commencing time and the degree of skin lesions in NC/Nga mice.
      OBJECTIVES: In the present study, we attempted to improve experimental conditions
      to induce stable skin lesions and to establish a more appropriate method. Methods
      NC/Nga mice were kept together with skin-lesioned mice during the experiment
      period (mixed-NC mice). The dermatitis scores of face, ears and rostral back were
      assessed. Scratching behaviour was measured using an apparatus, MicroAct
      (Neuroscience, Tokyo, Japan). Transepidermal water loss (TEWL) and serum total
      IgE levels were also measured. To observe the presence of mites, the skin of the
      rostral backs of the mixed-NC mice was stripped using cellulose tape. We also
      investigated the effects of fipronil (Wako, Osaka, Japan), an acaricidal
      compound, on skin lesions and scratching behaviour of these mixed-NC mice.
      RESULTS: In mixed-NC mice, skin lesions appeared from 2 weeks, worsened gradually
      and reached peak levels of a dermatitis score in 8 weeks. Scratching behaviour
      increased significantly from day 3. TEWL also increased from day 3, but total IgE
      increased from day 7. Mites were observed on the rostral backs of mixed-NC mice
      from day 3, and all mice had these mites on day 28. Giving pretreatment with
      fipronil (Wako), the skin lesions and scratching behaviour of mixed-NC mice was
      significantly suppressed. CONCLUSIONS: The findings of the present study suggest
      that the method of being kept together with skin-lesioned mice can induce stable
      skin lesions and scratching behaviour at an early stage, without skin lesions.
      This method could help investigate a more stable evaluation of the effects on
      symptoms of atopic dermatitis, and mechanisms of the itching. It was considered
      that parasitism of mites, not allergic reactions, was the pathogenesis of skin
      lesions and scratching behaviour in mixed-NC mice.

PMID- 16445771
TI  - Three-point checklist of dermoscopy: an open internet study.
AB  - BACKGROUND: In a pilot study, the three-point checklist of dermoscopy has been
      shown to represent a valid and reproducible tool with high sensitivity for the
      diagnosis of skin cancer in the hands of a small group of nonexperts. OBJECTIVES:
      To re-evaluate these preliminary results in a large number of observers
      independently from their profession and expertise in dermoscopy. METHODS: The
      study was conducted via the internet to provide worldwide access for
      participants. After a short web-based tutorial, the participants evaluated
      dermoscopic images of 165 (116 benign and 49 malignant) skin lesions (15 training
      and 150 test lesions). For each lesion participants scored the presence of the
      three-point checklist criteria (asymmetry, atypical network and blue-white
      structures). Kappa values, odds ratios, sensitivity, specificity and likelihood
      ratios were estimated. RESULTS: Overall, 150 participants joined the study. The
      three-point checklist showed good interobserver reproducibility (kappa value:
      0.53). Sensitivity for skin cancer (melanoma and basal cell carcinoma) was 91.0%
      and this value remained basically uninfluenced by the observers' professional
      profile. Only 20 participants lacking any experience in dermoscopy performed
      significantly more poorly, but the sensitivity was still remarkably high (86.7%)
      when considering that they were untrained novices in dermoscopy. The specificity
      was 71.9% and was significantly influenced by the profession, with dermatologists
      performing best. CONCLUSIONS: Our study confirms that the three-point checklist
      is a feasible, simple, accurate and reproducible skin cancer screening tool.

PMID- 16445772
TI  - Multiple senile lentigos of the face, a skin ageing pattern resulting from a life
      excess of intermittent sun exposure in dark-skinned caucasians: a case-control
      study.
AB  - BACKGROUND: Different patterns of skin ageing can be described depending on the
      predominant lesions, i.e. wrinkles, laxity, atrophy, senile lentigos (SLs), etc.
      They may correspond to different epidemiological contexts. OBJECTIVES: To
      identify and assess the epidemiological factors for a skin ageing pattern
      characterized by a high density of SLs on the face, or 'lentigo ageing pattern'
      (LAP). METHODS: An age- and sex-matched case-control study was conducted in
      individuals aged between 60 and 80 years, comparing cases (n = 118) with a very
      high number of SLs on the face for their age, and controls (n = 118) with no or
      very few SLs for their age. The cases and controls were recruited in two
      hospitals. RESULTS: In univariate and multivariate analysis, LAP was associated
      with skin types III and IV, with frequent sunburns, and with the part of the
      lifetime cumulative sun exposure which was received during vacations. Conversely,
      there was no link with the occupational and everyday exposures and the total
      cumulative exposure. LAP was associated with multiple solar lentigos of the upper
      back. No relationship was found with postmenopausal hormonal therapy, number of
      naevi, or freckles. CONCLUSIONS: Different epidemiological factors may account
      for the different skin ageing patterns. LAP seems to develop preferentially in
      dark-skinned caucasians who have repeatedly received intermittent and intense sun
      irradiations throughout their life, and have often developed solar lentigos on
      the upper back earlier in life, whereas the 'prominent wrinkling' pattern is
      known to affect light-skinned people and smokers with a life excess of continuous
      exposure.

PMID- 16445773
TI  - The presence of dominant T-cell clones in peripheral blood of patients with
      collagen vascular disorders: a prospective study of 97 cases.
AB  - BACKGROUND: T-lymphocyte dysfunction has been seldom investigated in collagen
      vascular disorders. The search for dominant T-cell clones has been scarcely
      reported, although the presence of such clones might be expected in disorders
      showing immune responses directed against a variety of autoantigens. OBJECTIVES:
      We conducted a systematic search for dominant T-cell clones in peripheral blood
      in patients with collagen vascular disorders. Patients and methods Ninety-seven
      patients with collagen vascular disorders were studied (7 cutaneous and 38
      systemic lupus erythematosus; 8 multiple morphea; 12 regional scleroderma; 32
      systemic sclerosis of the CREST type). A dominant T-cell clone was searched for
      in peripheral blood by polymerase chain reaction targeting the T-cell receptor
      gamma chain followed by a size analysis of amplified fragments. Peripheral blood
      from patients with nonlymphocyte-dependent disorders and matched by age and sex
      was assessed in the same conditions. Results in both groups were compared using
      nonparametric statistical tests. RESULTS: Overall, a circulating dominant T-cell
      clone was found in 52% of patients compared with 16.9% in controls. More
      precisely, such a dominant clone was present in 43% and 37% of cutaneous and
      systemic lupus erythematosus, respectively, in 75% of multiple morphea, 75% of
      regional scleroderma and 60% of CREST syndrome patients. The percentages in all
      subsets of patients were significantly higher than in the control group.
      CONCLUSIONS: The presence of a dominant T-cell clone in peripheral blood is
      significantly more frequent in collagen vascular disorders than in controls,
      especially in patients with scleroderma, whatever the clinical subset, which
      suggests T-cell involvement in the immune response dysfunction in these diseases
      classically characterized by disturbances of B lymphocytes. The relevance of such
      a dominant clone regarding diagnosis, pathomechanisms, long-term outcome and
      visceral prognosis of these diseases as well as therapeutic decisions remains to
      be evaluated.

PMID- 16445774
TI  - Mutation analysis in Irish families with glomuvenous malformations.
AB  - BACKGROUND: Glomuvenous malformations (GVMs) are rare bluish lesions that can
      affect the skin and mucosal surfaces. They represent defects in vasculogenesis.
      Lesions can occur sporadically or in an autosomal dominant mode of inheritance.
      Recent studies have shown that mutations in the glomulin gene (GLMN) on
      chromosome 1p21-22 are responsible for familial GVMs. OBJECTIVES: To search for
      mutations in GLMN in Irish families with GVMs. METHODS: We identified four Irish
      families with GVMs and confirmed linkage to chromosome 1p21-22 in these cases. We
      sequenced the glomulin gene in all affected and unaffected members of the
      families. Results Linkage analysis showed that affected individuals from the
      families shared a common haplotype. Mutation analysis revealed a delAAGAA
      mutation in exon 3 of the glomulin gene in all four families with GVMs.
      CONCLUSIONS: We confirm that mutations in the glomulin gene are responsible for
      GVMs and suggest a founder Irish mutation in the glomulin gene in four Irish
      families.

PMID- 16445775
TI  - Conventional histology vs. three-dimensional histology in lentigo maligna
      melanoma.
AB  - BACKGROUND: Conventional surgery for lentigo maligna melanoma (LMM) is based on
      normal histological evaluation. However, such evaluation leaves diagnostic gaps.
      In contrast, complete three-dimensional (3D) histology of excision margins
      permits accurate detection of continuously spreading tumour strands like those of
      LMM. These can be specifically excised in tumour-positive areas with smaller
      excision margins, and better cosmesis and function. To date there have been no
      controlled studies of micrographic surgery of LMM. OBJECTIVES: Clinical
      parameters and surgical strategies influencing the prognosis of patients with LMM
      were evaluated in a prospective study of melanoma patients in the Department of
      Dermatology of the University of Tubingen (1980-99). METHODS: The 292 LMMs
      comprised 7.4% of 3960 primary stage I and II melanomas treated during this
      period. One hundred and thirty-six patients in this group (46.6%) underwent
      surgery on the basis of 3D histology. RESULTS: The geometric mean excision
      margins were significantly smaller in the 3D histology group (P < 0.0001).
      Patients with micrographic surgery had fewer recurrences. Multivariate analysis
      of clinical, histological and surgical variables was carried out, and tumour
      thickness and 3D histology proved to be independent, significant factors for the
      prognosis of recurrence-free survival (relative risk, RR 2.08, P < 0.0001 and RR
      2.11, P = 0.0037, respectively). There were no melanoma-related deaths in the 3D
      histology group. All 16 melanoma-related deaths were observed among the 156
      patients of the conventional histology group (10.3%). CONCLUSIONS: Excision of
      LMM using 3D histology resulted in a twofold lower probability of recurrence and
      twofold smaller excision margins. 3D histology is a valuable diagnostic tool and
      can be used in the management of LMM because of the latter's pattern of
      continuous tumour spread.

PMID- 16445776
TI  - Programmed cell death of keratinocytes in infliximab-treated plaque-type
      psoriasis.
AB  - BACKGROUND: Tumour necrosis factor (TNF)-alpha blockade using infliximab, a
      chimeric anti-TNF-alpha antibody, is an effective treatment for plaque-type
      psoriasis, inducing remission in about 80% of patients. OBJECTIVES: To examine
      infliximab-induced programmed cell death (PCD) of keratinocytes in psoriatic
      plaques on serial skin biopsy samples. METHODS: Five patients with moderate to
      severe plaque-type psoriasis received infliximab infusions intravenously (5 mg
      kg(-1)) at weeks 0, 2 and 6. Biopsies of nonlesional and lesional skin (days 0,
      5, 14 and 21) were obtained. Conventional microscopy was used to examine the
      morphology of the psoriatic keratinocytes. In situ detection of apoptosis was
      performed by electron microscopy and by immunohistochemical staining with anti
      p53 and anti-caspase-3 antibodies. Results Infusion of infliximab induced a
      clinical response in all five patients with psoriasis, with a mean Psoriasis Area
      and Severity Index improvement of 24.8% already at day 5. This was accompanied by
      significant histopathological changes in the skin biopsy samples after infliximab
      treatment. Light and electron microscopic evaluation revealed apoptosis-like
      morphological changes in lesional keratinocytes, i.e. nuclear condensation,
      chromatin fragmentation and cytoplasmic vesiculation, visible already after the
      first infusion. These damaged keratinocytes stained positively for p53, but not
      for active caspase-3. CONCLUSIONS: The effects of infliximab in psoriasis extend
      beyond merely anti-inflammatory actions, and may include caspase-independent PCD
      of lesional keratinocytes. The PCD of keratinocytes may be an important mechanism
      that could explain at least in part the rapid and sustained therapeutic effect of
      infliximab in psoriasis.

PMID- 16445778
TI  - Melanomas in renal transplant recipients.
AB  - BACKGROUND: It is well documented that renal transplant recipients are at
      increased risk of developing skin cancers, in particular squamous cell
      carcinomas. Less extensively reviewed in the literature is the increased
      incidence of malignant melanoma. We have reviewed 10 patients in the Oxford renal
      transplant population who developed 12 melanomas following transplantation.
      OBJECTIVES: To determine the incidence and characteristics of melanoma in renal
      transplant recipients. METHODS: We reviewed the case notes and pathology of all
      patients who developed melanoma within the Oxford Renal Transplant Unit. The
      clinical details were recorded including date of transplant, immunosuppressive
      therapy, interval between transplant and melanoma, site of occurrence, history of
      sun exposure, type of clinician diagnosing the melanoma, history of other skin
      malignancies and outcome. From the histopathology we documented various
      prognostic factors. RESULTS: Ten patients developed 12 melanomas (one patient had
      three melanomas) from a population of 1874 transplanted patients. The total
      number of transplant years was 11 942.2. The incidence of melanoma in our
      population was 12 per 11 942.2 transplant years, which is approximately 8 times
      greater than the standardized rate for this region. We found that the mean
      interval between transplant and melanoma was approximately 11 years (median 8.5).
      A dermatologist was the diagnosing clinician in at least 67% of cases. Melanomas
      occurred on the trunk in the majority of cases (58%), followed by the upper limb
      (25%). All patients apart from one are alive with no recurrence of their
      melanoma. One patient died as a result of metastatic melanoma. The mean follow-up
      period following melanoma was 3.7 years. In all patients apart from the patient
      who died, the melanomas were < 1 mm Breslow thickness. That patient's melanoma
      was 4.5 mm thick. There was no precursor naevus in eight of the 12 melanomas. In
      two there was a precursor dysplastic naevus. In the cases in vertical growth
      phase the tumour-infiltrating lymphocyte response was absent in four cases and
      nonbrisk in one patient. CONCLUSIONS: In the Oxford transplant population studied
      melanomas occurred at approximately 8 times the rate in the general population.
      This is the highest rate reported in the literature. The patients had a better
      outcome than reported previously. This may be due to detection at a relatively
      early stage. Renal transplant recipients attend dedicated dermatology clinics in
      Oxford, which may have contributed to the early diagnosis and good outcome.

PMID- 16445777
TI  - Polymorphisms within the CTLA4 gene are associated with infant atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is one of the most common childhood disorders.
      It can have a significant impact on the physical and psychological well-being of
      affected individuals. Although environmental triggers are important, AD also has
      a strong genetic component. Identifying genes associated with AD may help to
      understand better the basis of this disorder and its relationship with other
      allergic disorders such as asthma. OBJECTIVES: Polymorphisms in the gene encoding
      the inhibitory CTLA4 receptor, an important regulator of T cells, are associated
      with asthma as well as autoimmune disorders. We have now tested whether
      polymorphisms in the CTLA4 gene are also associated with early childhood AD.
      METHODS: A family-based cohort of 112 children and their parents was recruited
      from Western Sydney, Australia. All children were seen by a paediatric
      dermatologist and presented with AD within the first 3 years of life. Using the
      transmission disequilibrium test, individual and haplotypic associations with the
      +49 and CT60 polymorphisms in exon 1 and the 3' nontranslated DNA of the CTLA4
      gene were tested. RESULTS: Single tests of association revealed significant
      association of the +49(A) [P = 0.037, odds ratio (OR) 1.59, 95% confidence
      interval (CI) 1-2.55] and borderline significance of the CT60(A) alleles (P =
      0.055, OR 1.51, 95% CI 1-2.38). Significant association of the +49(A)/CT60(A)
      haplotype was detected (P = 0.002, OR 1.78, 95% CI 1.2-2.65). CONCLUSIONS:
      Polymorphisms within the gene encoding CTLA4 were associated with early onset
      infant AD. This is in agreement with findings from asthmatic cohorts, suggesting
      that the +49(A)/CT60(A) haplotype is a genetic risk factor common to asthma and
      AD.

PMID- 16445779
TI  - Clinical, dermoscopy and histological correlation study of melanotic
      pigmentations in excision scars of melanocytic tumours.
AB  - BACKGROUND: Melanotic pigmentations in scars consecutive to the excision of
      melanocytic tumours can be secondary to a reactive phenomenon related to the scar
      tissue or to a recurrence of the melanocytic lesion excised in the first case.
      Recurrent naevi may sometimes adopt unusual features that make them difficult to
      differentiate from a melanoma. OBJECTIVES: To describe the clinical, dermoscopic
      and histological features of melanotic pigmentations in scars consecutive to the
      excision of melanocytic tumours, and to correlate the histological diagnosis with
      the dermoscopic features. METHODS: This was a prospective cohort study using
      macrophotography, dermoscopy and histopathological study. Ninety-five melanotic
      pigmentations (77 patients) in scars secondary to the excision of melanocytic
      tumours were prospectively collected in the Department of Dermatology at the
      Instituto Valenciano de Oncologia in Valencia, Spain. Histopathological study was
      performed in 57 scars. RESULTS: Thirteen dermoscopic structures were identified.
      Four criteria allowed a differentiation between reactive and specific melanocytic
      pigmentations. Presence of globules and presence of heterogeneous pigmentation
      were features associated with specific melanocytic pigmentations (P < 0.0001).
      Presence of a regular network and presence of streaks were more frequently found
      in reactive pigmentations (P = 0.023 and 0.026, respectively). CONCLUSIONS:
      Dermoscopic examination of melanotic pigmentations in excision scars of
      melanocytic tumours provides useful information about the origin of that
      pigmentation. Based on such information, recurrent naevi can be differentiated
      from reactive pigmentations in most cases. Excision and histopathological
      diagnosis continue to be imperative in some cases of recurrent naevi with
      atypical clinical features.

PMID- 16445780
TI  - Distinct phenotypic changes between the superficial and deep component of giant
      congenital melanocytic naevi: a rationale for curettage.
AB  - BACKGROUND: Giant congenital melanocytic naevi (GCMN) convey a 14-fold increased
      melanoma risk. In contrast, medium congenital melanocytic naevi (MCMN) are rarely
      associated with malignant transformation. Management of patients with GCMN is
      challenging and there is no consensus on the most appropriate strategy for
      treating these patients. OBJECTIVES: To provide a rationale for performing
      curettage of GCMN in the neonatal period in order to reduce the risk of malignant
      transformation to melanoma. METHODS: Twenty-six infants with GCMN who underwent
      biopsies before excisional surgery (n = 7) or curettage (n = 19) during the past
      14 years (Academic Hospital, Vrije Universiteit Brussel) and 10 MCMN patients who
      underwent excision biopsies (Radboud University Nijmegen Medical Centre) were
      included in this study. Using these biopsies, we performed genetic and detailed
      immunohistochemical evaluations of changes that are associated with malignant
      transformation. Variables of interest included melanoma-associated BRAF
      mutations, proliferative activity, vascularity, cellular context and
      extracellular matrix architecture. RESULTS: GCMN and MCMN did not show oncogenic
      BRAF mutation and displayed similar features with respect to the amount of
      nonmelanocytic cells within the naevus and matrix architecture. Naevus cells in
      the superficial component of the GCMN, however, were more proliferative, and this
      component was more vascular compared with its deep component and with MCMN. In
      this study, none of the 19 newborn patients who underwent curettage developed a
      melanoma within a mean follow-up time of 7 years. CONCLUSIONS: The data presented
      here support the idea that curettage of GCMN in neonates has the potential for
      lowering the risk of developing cutaneous melanoma by not only obtaining an
      important numerical reduction of naevus cells but also removing the 'active'
      melanocytes.

PMID- 16445781
TI  - The occurrence of residual or recurrent squamous cell carcinomas in organ
      transplant recipients after curettage and electrodesiccation.
AB  - BACKGROUND: Organ transplant recipients frequently develop multiple squamous cell
      carcinomas (SCCs). Surgical excision and Mohs micrographic surgery are frequently
      used treatments for these carcinomas; however, curettage and electrodesiccation
      are a useful alternative in these patients. OBJECTIVES: To evaluate the efficacy
      of curettage and electrodesiccation for the treatment of appropriately selected
      low-risk SCCs in organ transplant recipients at different sites. METHODS: Between
      April 1989 and December 2004, 211 SCCs in 48 organ transplant recipients were
      treated by curettage and electrodesiccation. Only histologically confirmed SCCs
      were considered in this study. The charts of these patients were retrospectively
      reviewed and checked for the rate of residual or recurrent SCCs. The occurrence
      of residual or recurrent SCCs at different locations after treatment of SCCs with
      curettage and electrodesiccation was estimated with Kaplan-Meier survival
      analysis. RESULTS: The mean follow-up time after curettage and electrodesiccation
      of the individual SCCs was 50 months (median 41; range 3-186). In total, 13
      residual or recurrent SCCs were observed in 10 patients. The overall rate of
      residual or recurrent SCCs was 6%, with 7% for SCCs on the dorsum of the hands or
      fingers, 11% for SCCs on the head and neck, 0% for the forearms, and 5% for the
      remaining nonsun-exposed areas (shoulder, legs). No major clinical or cosmetic
      adverse events were registered after treatment. CONCLUSIONS: In organ transplant
      recipients with many SCCs curettage and electrodesiccation can be a safe therapy
      for appropriately selected low-risk SCCs, with an acceptable cure rate.

PMID- 16445782
TI  - A population-based study of skin cancer incidence and prevalence in renal
      transplant recipients.
AB  - BACKGROUND: Cancers occurring following solid organ transplantation are a rapidly
      growing public health concern. Defining the extent of the problem has been
      limited by surveillance systems with incomplete registration of cases and the
      paucity of reliable national incidence data. OBJECTIVES: To determine the
      incidence of all cancers following renal transplantation and to make a detailed
      examination of trends and patterns associated with postrenal transplant skin
      cancers. METHODS: Integration of data from the national renal transplant database
      and the national cancer registry in Ireland enabled accurate determination of the
      number of renal transplant recipients (RTRs) with skin cancers and other
      malignancies in the time period 1 January 1994 to 31 December 2001. RESULTS: We
      demonstrated a biphasic increase in skin cancer incidence following renal
      transplantation, determined by the age at transplantation. There was a steady
      increase in risk for older RTRs (age 50+ years) from year 2 post-transplant,
      whereas the increased risk in younger RTRs (age < 50 years) occurred later but
      much more significantly, reaching 200 times the risk for an age-matched
      nontransplanted population by year 6 post-transplant. The number of nonmelanoma
      skin cancers (NMSCs) registered in RTRs accounted for 1% of all NMSCs registered
      nationally over the study period. The standardized incidence rates for invasive
      NMSC (33-fold increase) and in situ carcinoma of the skin (65-fold increase) were
      significantly increased (P < 0.05). The risk for invasive squamous cell carcinoma
      (SCC) was increased 82-fold compared with the nontransplanted population. Male
      RTRs were at particular risk of invasive SCC at sun-exposed sites such as the
      scalp and the external ear. Risk of malignant melanoma and Kaposi sarcoma were
      also increased relative to the nontransplanted population. CONCLUSIONS: This
      comprehensive national study illustrates how rates of skin cancer in Irish RTRs
      have influenced the national incidence of skin cancer. The high incidence of SCC,
      basal cell carcinoma and Bowen's disease in the early post-transplant period for
      older patients and the cumulative risk in younger patients with increased
      duration of transplantation highlight the importance of implementing early and
      continued cancer surveillance regimens post-transplant.

PMID- 16445783
TI  - The course of eczema in children aged 5-7 years and its relation to atopy:
      differences between boys and girls.
AB  - BACKGROUND: The role of atopy in the pathophysiology of eczema is still under
      debate. The concept and analyses of the nonatopic and atopic subtypes of eczema
      have gained increasing interest in recent studies. The course of these subtypes
      and differences between boys and girls have not been investigated so far.
      OBJECTIVES: To examine the course of nonatopic and atopic eczema in preschool
      children from Germany with regard to sex. METHODS: Repeated cross-sectional
      studies were performed in 5-7-year-old preschool children from Germany between
      1994 and 2000. Individuals with eczema were identified by a dermatological
      examination. In addition to a questionnaire, skin prick tests and analyses of
      serum IgE antibodies against seven and five environmental allergens,
      respectively, were performed. Atopy was defined by sensitization to at least one
      of five common aeroallergens (birch, grass and mugwort pollen, house dust mites,
      cat dander). In part of the study population investigations of spare time
      behaviour and skin function were carried out (including stratum corneum hydration
      and skin surface pH). RESULTS: A total of 2693 girls and 2783 boys underwent a
      full dermatological examination of the skin and determination of sensitization.
      Among the girls, 8.7% demonstrated eczema clinically at the day of investigation
      in contrast to 6.1% of the boys. In girls, early onset eczema (< 2 years of age)
      was strongly related to atopy at age 5-7 years [odds ratio (OR) 3.7; 95%
      confidence interval (CI) 2.7-5.1], whereas late-onset eczema (> or = 2 years of
      age) was not (OR 1.0; 95% CI 0.7-1.5). Boys were more often atopic at the age of
      5-7 years than girls (28.3% vs. 20.6%), and early and late-onset eczema were
      related to atopy without such a difference (OR 2.8, 95% CI 2.0-4.0; OR 1.9, 95%
      CI 1.3-2.8, respectively). The excess of current eczema in 5-7-year-old girls
      compared with boys was related to the nonatopic type. The higher susceptibility
      of girls in that age group to develop eczema was reflected by the skin
      physiological examination: even girls without eczema had significantly higher
      skin surface pH and lower stratum corneum hydration than boys. Additionally,
      questionnaire data revealed that girls more often than boys predominantly played
      indoors, which was associated with more eczema. CONCLUSIONS: Atopy and eczema
      develop differently in boys and girls. Boys are more often atopic, whereas girls
      suffer significantly more often from eczema without relation to atopy. The
      nonatopic type of eczema in preschool girls is noticed predominantly after their
      second birthday. Genetic and lifestyle factors may contribute to this difference.

PMID- 16445784
TI  - Effect of childhood eczema and asthma on parental sleep and well-being: a
      prospective comparative study.
AB  - BACKGROUND: The psychological impact of childhood atopic eczema on parents and
      carers is poorly quantified. Objectives To compare the impact of caring for a
      child with atopic eczema vs. asthma on parents' sleep and well-being. METHODS:
      Ninety-two parents of 55 children who had moderate to severe atopic eczema or
      asthma took part in this prospective, questionnaire-based study. It was conducted
      at regional eczema and asthma outpatient clinics within a U.K. tertiary
      paediatric hospital. The main outcome measures were the number and duration of
      parents' sleep disturbances, as well as their anxiety and depression scores.
      RESULTS: Mothers caring for children with atopic eczema lost a median of 39 min
      of sleep per night and fathers lost 45 min sleep per night. This compared with a
      median of 0 min sleep lost by parents who had children with asthma (P < 0.001).
      These differences were independent of the age of the children, and whether the
      child came from a single-parent or two-parent family. There was a direct
      correlation between the severity of sleep disturbance and the level of maternal
      anxiety (rho = 0.58; P = 0.002) and depression (rho = 0.73; P < 0.001), as well
      as the level of paternal anxiety (rho = 0.59; P = 0.01). CONCLUSIONS: Compared
      with looking after a child with chronic asthma, caring for a child with chronic
      atopic eczema was associated with greater parental sleep disturbances. Disruption
      to parental sleep correlated with anxiety levels and, in the case of mothers,
      depression scores.

PMID- 16445785
TI  - Efficacy of 8-methoxypsoralen vs. 5-methoxypsoralen plus ultraviolet A therapy in
      patients with mycosis fungoides.
AB  - BACKGROUND: Psoralen plus ultraviolet (UV) A (PUVA) is the standard treatment for
      early stage mycosis fungoides (MF). When 8-methoxypsoralen (8-MOP) is used in
      PUVA therapy, it often produces intolerance reactions such as nausea, vomiting
      and headache. OBJECTIVES: To investigate whether 5-methoxypsoralen (5-MOP) is a
      safe and effective alternative to 8-MOP in PUVA therapy for MF. METHODS: A
      retrospective database search and chart review was done to identify patients with
      MF who received PUVA with either 5-MOP or 8-MOP as initial monotherapy at our
      institution. Between 1990 and 2004, 14 patients [seven men and seven women; mean
      age 70 years, range 51-82; National Cancer Institute disease stages IA (n = 6)
      and IB (n = 8)] received 5-MOP, and 24 patients [21 men and three women; mean age
      58 years, range 28-89; disease stages IA (n = 11), IB (n = 12) and IIB (n = 1)]
      received 8-MOP. RESULTS: Twelve of 14 patients (86%) in the 5-MOP group and 22 of
      24 (92%) in the 8-MOP group had a complete response to PUVA. These two subgroups
      of complete responders did not differ significantly in terms of PUVA therapy
      duration, number of treatments or cumulative UVA dose. They also did not differ
      significantly in terms of relapse-free rate [8% (one of 12) vs. 23% (five of 22)]
      or time to relapse [17 months (range 4-31) vs. 14 months (range 4-33)]. Moreover,
      PUVA maintenance therapy with either 5-MOP or 8-MOP in a subset of patients [26%
      (nine of 34)] did not affect long-term relapse-free status either. CONCLUSIONS: 5
      MOP and 8-MOP have comparable therapeutic efficacy when used in PUVA therapy for
      MF.

PMID- 16445786
TI  - Conjoint analysis: a novel, rigorous tool for determining patient preferences for
      topical antibiotic treatment for acne. A randomised controlled trial.
AB  - BACKGROUND: Acne vulgaris is an extremely common skin disorder that can be
      treated effectively with drugs that are currently available. Poor compliance,
      however, is a major factor in the high failure rates seen in acne treatment.
      Compliance might be enhanced by considering patient preferences for acne
      medications. Conjoint analysis is well suited for the study of patient
      preferences in healthcare, but is novel to the field of dermatology. OBJECTIVES:
      The study aimed to determine and compare patient preferences for four topical
      antibiotics used for 1 week, once or twice daily, to treat acne vulgaris.
      METHODS: A randomised, phase IV, single-centre, cross-over study was performed
      using conjoint analysis and a traditional patient questionnaire. Over 4 weeks,
      the patients used each of four topical antibiotics for 1 week: erythromycin/zinc
      solution, clindamycin phosphate lotion, benzoyl peroxide (BP)/erythromycin gel
      (each applied twice daily) and clindamycin phosphate gel (applied once daily).
      The conjoint analysis examined five different attributes of acne medications:
      form, storage, product life once opened, method of application and regimen (each
      with two or three possible options). From 108 possible permutations of the five
      attributes, 16 hypothetical medications were selected at random and described on
      printed cards. Pre- and post-treatment, the patients ranked the cards in order of
      preference and rated each hypothetical product based on their likelihood to use
      it. For each patient, product 'utilities' were then calculated by multiple
      regression. The patients also completed a patient acceptability questionnaire, by
      which they rated the product acceptability after 1 week of treatment with each of
      the four topical antibiotics. The patients later ranked the medications in order
      of preference after using all four treatments. Adverse events were recorded in
      diary cards to assess tolerability. RESULTS: Of 67 patients recruited, 64 used
      all four medications and completed the study. The conjoint analysis found that a
      gel formulation, room temperature storage, product life of up to 18 months once
      opened, application with fingers and once-daily regimen were the options ranked
      first for the five product attributes. According to the ranking order (out of
      108) for the combination of attributes representing the four study medications,
      clindamycin phosphate gel had the highest rankings (6 and 1 pre- and post
      treatment, respectively) and BP/erythromycin gel had the lowest rankings (93 and
      70 pre- and post-treatment). The rankings of clindamycin phosphate lotion and
      erythromycin/zinc solution worsened from pre- to post-treatment, indicating a
      shift in patient preference after they experienced products 'in-use' during the
      study. Based on the questionnaire, clindamycin phosphate gel was liked best by
      the highest proportion of patients (33%). In terms of overall satisfaction, the
      order of preference was: (i) clindamycin phosphate gel, (ii) clindamycin
      phosphate lotion, (iii) BP/erythromycin gel and (iv) erythromycin/zinc solution.
      Adverse events related to medication occurred most frequently with
      erythromycin/zinc solution and BP/erythromycin gel. Clindamycin phosphate gel was
      the only product not associated with any episodes resulting in a change of
      medication or dose. CONCLUSIONS: Conjoint analysis provided a convenient,
      reliable tool for assessing patient preferences for topical antibiotics used to
      treat acne. The patients clearly preferred a gel formulation that could be
      applied with the fingers once daily and stored at room temperature for as long as
      18 months. One product (clindamycin phosphate gel) combined all five of the
      preferred attributes, a preference confirmed by the simulated product rankings.
      These findings of the conjoint analysis are consistent with the safety profiles
      and the results of the traditional questionnaire.

PMID- 16445787
TI  - Levocetirizine in the treatment of chronic idiopathic urticaria: a randomized,
      double-blind, placebo-controlled study.
AB  - BACKGROUND: Chronic urticaria is a common skin condition. It is frequently a
      disabling disease because of the persistence of clinical symptoms, the
      unpredictable course and its negative influence on the quality of life.
      OBJECTIVES: To determine whether levocetirizine is efficacious in the treatment
      of chronic idiopathic urticaria. METHODS: A randomized, double-blind, placebo
      controlled study was conducted in 106 patients with a diagnosis of chronic
      idiopathic urticaria. A 1-week single blind placebo run-in period (baseline) was
      followed by a 6-week double blind active treatment period. The patients were
      randomized to receive one of the following treatments once daily: (a) oral
      levocetirizine 5 mg, or (b) oral placebo. The study ended after another 1-week
      single blind placebo washout period. RESULTS: The evaluable population consisted
      of 100 patients. Levocetirizine administered once daily is effective and well
      tolerated in the treatment of the symptoms of chronic idiopathic urticaria and in
      improving the patient's quality of life. Levocetirizine was superior to placebo
      in reducing the mean total symptoms score as well as individual symptoms, the
      number of daily episodes and the number of weals, the overall severity of
      symptoms and the quality of life. The significant beneficial effects of
      levocetirizine lasted only during the active trial, while at follow-up there was
      a significant worsening of all the variables evaluated in this study, after the
      end of the active trial (week 7). CONCLUSIONS: A global assessment indicates that
      levocetirizine 5 mg once daily is an effective agent in patients with chronic
      idiopathic urticaria, as its action provides a rapid and satisfactory control of
      the symptoms and measures of subjective disease, although this is limited to the
      duration of treatment.

PMID- 16445788
TI  - Melanoma screening clinics: are we detecting more melanomas or reassuring the
      worried well?
AB  - BACKGROUND: Melanoma screening clinics (MSCs) have been set up in the U.K. to
      help allay public anxiety about potential skin cancers, and to permit the early
      detection of thin melanomas, thus improving prognosis. Public health campaigns
      have led to increased awareness of melanoma and increased numbers of referrals to
      MSCs. OBJECTIVES: To determine whether the MSC has had an impact on the number
      and thickness of melanomas detected over the past 8 years. METHODS: Data was
      analysed retrospectively for all patients attending the MSC since it was set up
      in 1997, until the end of 2004. We categorized patients with melanoma according
      to Breslow thickness, examined trends in referral to the clinic and analysed
      changes in the proportion of patients with a new diagnosis of melanoma. RESULTS:
      There were 15 970 patients who attended for screening; 403 primary invasive
      melanomas were detected, and 190 in situ melanomas. The number of new patients
      seen each year increased by over 230%, although the proportion of patients with
      melanoma detected declined. The Breslow thickness did not change over time.
      CONCLUSIONS: Our experience suggests that public awareness has increased and that
      the general practitioner threshold for referral has fallen but there has been no
      reduction in the thickness of those melanomas diagnosed.

PMID- 16445789
TI  - Hereditary angio-oedema with normal C1 inhibitor in a family with affected women
      and men.
AB  - Recurrent angio-oedema is a sign of various acquired and inherited disease
      entities, including hereditary angio-oedema types I and II that result from a
      genetic deficiency of C1 inhibitor, and a recently described type of dominantly
      inherited angio-oedema, which does not show a deficiency of C1 inhibitor. Until
      now, this new type of hereditary angio-oedema, designated as hereditary angio
      oedema type III, has been assumed to be a disorder specific to females. We now
      describe a four-generation family with dominantly inherited angio-oedema and
      normal C1 inhibitor in which, in contrast to all previous observations, not only
      five female but also three male family members were clinically affected. One male
      patient was mainly affected following the intake of angiotensin-converting enzyme
      inhibitors. Our current observation leads to new considerations about the
      classification of hereditary angio-oedema with normal C1 inhibitor. Either
      hereditary angio-oedema with normal C1 inhibitor can be an entity affecting
      females predominantly, but not exclusively; in that case, men appear to have a
      much reduced chance of clinical manifestations. Alternatively, our present
      observation of hereditary angio-oedema with normal C1 inhibitor affecting both
      sexes may represent a new disease entity, presumably with a different underlying
      defect.

PMID- 16445790
TI  - Preimplantation genetic diagnosis of skin fragility-ectodermal dysplasia
      syndrome.
AB  - Skin fragility-ectodermal dysplasia syndrome is an autosomal recessive disorder
      caused by loss-of-function mutations in the desmosomal protein, plakophilin 1.
      Clinically, there may be considerable morbidity from extensive skin erosions and
      painful fissures on the palms and soles. In the absence of any specific
      treatment, prenatal diagnosis is an option for couples at reproductive risk of
      recurrence. In 2000, we developed and applied a single cell nested polymerase
      chain reaction protocol to test one couple for compound heterozygous plakophilin
      1 gene mutations by preimplantation genetic diagnosis (PGD). Although pregnancy
      was established, an unrelated trisomy 22 led to a spontaneous abortion. However,
      eight embryos of known genetic status were cryopreserved at that stage, and we
      planned to undertake subsequent frozen embryo replacement cycles that might lead
      to the birth of an unaffected child in this family. Embryo cryopreservation was
      carried out in June 2000 using standard protocols in a three-step freezing
      procedure. Four embryos were thawed in March 2003, one of which was viable and
      was used in a frozen embryo replacement cycle, but pregnancy did not occur. The
      remaining four embryos were thawed in February 2004, two of which were viable
      (both carriers of the paternal mutation) and these were used in a second frozen
      embryo replacement cycle, and a singleton pregnancy was established. The child's
      plakophilin 1 genotype was assessed by direct nucleotide sequencing across the
      site of both potential mutations. Following two frozen embryo replacement cycles,
      and almost 4 years after the initial embryo biopsy and mutation analysis, a
      pregnancy was achieved that progressed to term with the birth of a healthy baby
      girl. Nucleotide sequencing of cord blood DNA, taken immediately after delivery,
      showed that the child was a heterozygous carrier of the paternal mutation but not
      of the maternal mutation. This case demonstrates the value of embryo
      cryopreservation, which can increase the number of embryo replacement procedures
      and hence the cumulative pregnancy rate per retrieval cycle. Moreover, this is
      the first report of successful full-term pregnancy and birth of a healthy baby
      following exclusion of a severe genodermatosis by PGD. The successful outcome of
      PGD in this case illustrates what is technically possible for couples at risk of
      recurrence of a severe inherited skin disease.

PMID- 16445792
TI  - Medulloblastoma metastasizing to the skin.

PMID- 16445791
TI  - Expression of bone morphogenetic protein-7 in human scalp skin and hair
      follicles.

PMID- 16445793
TI  - Rapidly progressive classic Kaposi sarcoma in an adolescent: response to
      interferon alfa therapy and biological correlates.

PMID- 16445794
TI  - Omeprazole-induced dermatomyositis.

PMID- 16445795
TI  - Routine, rapid, noninvasive diagnosis of viral skin exanthems.

PMID- 16445798
TI  - Thalidomide, semen distribution, teratogenicity... and cost.

PMID- 16445796
TI  - Reactive intravascular histiocytosis associated with tonsillitis.

PMID- 16445799
TI  - Thin primary melanoma: are we all treating it the same?

PMID- 16445800
TI  - Complete resolution of dermatitis herpetiformis with the Atkins' diet.

PMID- 16445801
TI  - Photocarcinogenic risk of narrowband ultraviolet B (TL-01) phototherapy: early
      follow-up data.

PMID- 16445802
TI  - Fumaric acid esters in psoriasis.

PMID- 16445803
TI  - Amicrobial pustulosis with antinuclear antibodies and rheumatoid factor.

PMID- 16445804
TI  - Occupational photoallergic contact dermatitis in a pharmaceutical worker
      manufacturing carprofen, a canine nonsteroidal anti-inflammatory drug.

PMID- 16445805
TI  - Reply to 'Digital dermoscopy analysis and internet-based program for
      discrimination of pigmented skin lesion dermoscopic images'.

PMID- 16445807
TI  - Human papillomavirus in melanoma.

PMID- 16445808
TI  - Congenital candidal onychomycoses: effective cure with ciclopirox olamine 8% nail
      lacquer.

PMID- 16445811
TI  - Emerging viral diseases and infectious disease risks.
AB  - New pathogens and antimicrobial-resistant forms of older pathogens continue to
      emerge, some with the potential for rapid, global spread and high morbidity and
      mortality. Pathogens can emerge either through introduction into a new population
      or when the interaction with the vector changes; emergence is also influenced by
      microbiological adaptation and change, global travel patterns, domestic and wild
      animal contact and other variants in human ecology and behaviour. Quick, decisive
      action to detect and control novel pathogens, and thereby contain outbreaks and
      prevent further transmission, is frequently hampered by incomplete or inadequate
      data about a new or re-emerging pathogen. Three examples of pathogens that are
      current causes for human health concern are avian influenza, West Nile virus
      (WNV) and the severe acute respiratory syndrome (SARS) coronavirus. Pathogens
      directly or indirectly transmitted by aerosolized droplets, such as avian
      influenza and SARS, pose considerable containment challenges. Rapid screening
      tests for other newly described pathogens such as WNV require time for
      development and may be <100% reliable. The importance of vigilance in the
      detection and control of newly recognized infectious threats cannot be
      overstressed. The presence of infectious agents in the blood supply could again
      have a significant impact on the safe use of both blood and blood-derived
      products in the care of patients with haemophilia, as did the human
      immunodeficiency virus in the 1980s. Emerging pathogens will continue to be a
      reality requiring the collaborative efforts of public health and individual
      healthcare providers worldwide to contain outbreaks and prevent transmission.

PMID- 16445812
TI  - Variant Creutzfeldt-Jakob disease: risk of transmission by blood transfusion and
      blood therapies.
AB  - In the last decade, a new variant of the human prion disease Creutzfeldt-Jakob
      disease (now known as variant CJD or vCJD) was identified and causally linked to
      dietary exposure to bovine spongiform encephalopathy (BSE) during the 1980s and
      early 1990s. Preliminary studies in animal models suggest that prions can be
      transmitted by blood. Based on two recent reports of iatrogenic vCJD transmission
      by blood transfusion in humans, a Department of Health-sponsored risk assessment
      warned that recipients of plasma therapies are now at risk of contracting vCJD
      from potentially infected donors. It is believed that all the population may be
      susceptible to vCJD infection, although clinical cases have so far occurred only
      in methionine homozygotes at codon 129 in the human prion protein gene. A non
      invasive blood-based diagnostic assay is urgently needed. Because the incubation
      period may be upwards of 40 years and there is no reliable screening test, it is
      currently unknown how many people may be in an asymptomatic phase of vCJD
      infection in the UK. However, there remains a distinct possibility that some
      infected patients may never develop clinical symptoms but will remain
      asymptomatic carriers who can potentially transmit the disease to other
      individuals. Therefore, screening of infectious individuals will be a critical
      component for individuals who rely on blood transfusions and/or blood therapies.
      In the absence of screening tests or effective therapies to treat this disease, a
      formidable worldwide public health challenge lies ahead to prevent new
      infections, accurately assess infection rates and treat infected patients.

PMID- 16445813
TI  - Clinical implications of emerging pathogens in haemophilia: the variant
      Creutzfeldt-Jakob disease experience.
AB  - The impact of variant Creutzfeldt-Jakob disease (vCJD) on the clinical practice
      of haemophilia in the UK is coloured by the haemophilia community's experience of
      hepatitis C virus and human immunodeficiency virus (HIV) transmission via plasma
      derived therapies in the 1980s, when the delay in recognizing and acting on the
      potential risks cost many patients their lives and left others to manage another
      chronic disease. This crisis prompted organisations such as the United Kingdom
      Haemophilia Centre Doctors' Organisation to advocate for the introduction of
      haemophilia therapies that would not be susceptible to contamination with blood
      borne pathogens. After the identification of vCJD in 1996, a number of public
      health measures were taken in response to a government-sponsored vCJD risk
      assessment, and following reports of transfusion-transmission of vCJD, additional
      guidelines have been developed to prevent person-to-person transmission, some of
      which may impact the quality and availability of medical and surgical care.
      Variant CJD has had a significant negative effect on the UK haemophilia
      community, shaking patient confidence in the therapies they have received over
      the last 21 years, affecting the quality of care and creating the risk of
      stigmatizing the community as it was in the 1980s. As with HIV and vCJD, emerging
      blood-borne infectious agents will likely affect blood and blood-derived
      therapies well before we become aware of its presence. As a result, only
      therapies with the lowest level of risk should be used for care of patients with
      haemophilia.

PMID- 16445814
TI  - The physician's role in selecting a factor replacement therapy.
AB  - Over the past 20 years, transmissions of human immunodeficiency virus (HIV),
      hepatitis B virus or hepatitis C virus have been virtually eliminated from plasma
      derived or recombinant therapy in the USA, a record that can be largely
      attributed to the use of effective screening and inactivation technologies for
      known pathogens. The next significant threat will likely come from the emergence
      of a new, blood-borne infectious disease, perhaps one transmitted by a non-lipid
      enveloped virus or prion, for which current inactivation methods are ineffective.
      Following the HIV crisis of the 1980s, government, patient advocacy groups,
      medical and scientific communities and the manufacturers of clotting therapies
      can learn from the past and approach potential threats from emerging pathogens in
      a proactive and productive manner. For clinicians, this includes actively
      engaging patients in a dialogue about all the factors that may influence their
      choice of clotting factor therapies, including emerging pathogens, patient
      convenience, consistency and reliability of supply, relative cost/benefit ratios,
      reimbursement issues (where applicable), patient preference and brand loyalty. It
      is our obligation as healthcare providers to understand potential risks and help
      make proactive decisions with our patients, decisions that often must be made in
      an environment of scientific uncertainty. Threats from infectious agents that
      were once deemed theoretical can, and often do, ultimately become real, with
      serious implications for morbidity and mortality.

PMID- 16445816
TI  - Immunohistochemical characterization of glomerular inflammatory cells and
      expression of adhesion molecules in anti-glomerular basement membrane (anti-GBM)
      glomerulonephritis induced in WKY rats with monoclonal anti-GBM antibodies of
      different subclasses.
AB  - According to previous report, adhesion of CD8-positive cells and macrophages to
      glomerular endotherial cells through the lymphocyte function-associated antigen-1
      (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway is crucial for the
      initiation and subsequent progression of anti-glomerular basement membrane (anti
      GBM) antibody-induced glomerulonephritis (anti-GBM nephritis) in WKY rats. In the
      present study glomerular inflammatory cell infiltration and LFA-1/ICAM-1
      expression were examined in anti-GBM nephritis induced in WKY rats with
      monoclonal anti-GBM antibodies of different subclasses: IgG1, IgG2a, and IgG2b.
      The IgG2a and IgG2b subclasses induced significant proteinuria from day 3 as
      compared with the IgG1 subclass. Glomerular infiltration of macrophages and CD8
      positive cells after administration of IgG2a and IgG2b subclass antibodies was
      significantly elevated compared to that for the IgG1 subclass. The intensity of
      glomerular ICAM-1 immunostaining by the IgG2a and IgG2b subclass antibodies
      tended to be stronger than that by the IgG1 subclass. Glomerular LFA-1-positive
      cell infiltration by the IgG2a and IgG2b subclasses was significantly higher than
      that of the IgG1 subclass. These results demonstrate that monoclonal antibodies
      belonging to the IgG2a and IgG2b subclasses strongly induce glomerular
      infiltration of inflammatory cells and expression of adhesion molecules in rat
      anti-GBM nephritis.

PMID- 16445817
TI  - Immunohistochemical study of the expression of adhesion molecules in ovarian
      serous neoplasms.
AB  - To clarify possible roles of adhesion molecules including E-cadherin, beta- and
      gamma-catenin, CD44s, CD44v6, CD56, and CD99 in ovarian serous neoplasms, an
      immunohistochemical study was undertaken for 23 benign, 40 borderline, and 95
      malignant ovarian serous neoplasms using tissue microarray (TMA). Significantly
      reduced expression of E-cadherin, and overexpression of CD44s, CD56, and CD99
      were more frequently observed in adenocarcinomas than in benign and borderline
      tumors. Expression of CD44v6 and nuclear beta- and gamma-catenin were detected
      only in borderline tumors and adenocarcinomas. Reduced expression of E-cadherin
      was also correlated with high tumor grade (P=0.03), presence of peritoneal
      seeding (P=0.03), and low overall survival rate (P=0.02). Overexpression of CD44s
      was significantly associated with high tumor grade (P=0.04), advanced stage
      (P=0.03), and low overall survival rate (P=0.02). CD56 was increasingly expressed
      in the case of advanced stage (P=0.005) and peritoneal seeding (P=0.001). Nuclear
      staining for gamma-catenin was correlated with tumor progression (P=0.004) and
      advanced International Federation of Gynecology and Obstetrics (FIGO) stage
      (P=0.02). Only CD44s expression and stage were correlated with overall survival
      in multivariate study. These results suggest that although E-cadherin, CD44s,
      CD56, and nuclear gamma-catenin immuno-expression seem to be useful prognostic
      markers for serous neoplasm of the ovary, CD44s expression and FIGO stage are
      independent prognostic factors.

PMID- 16445818
TI  - Pancreatic, hepatic, splenic, and mesenteric mucinous cystic neoplasms (MCN) are
      lumped together as extra ovarian MCN.
AB  - Mucinous cystic neoplasms (MCN) of the pancreas are mucin-producing cystic tumors
      with an ovarian-like stroma (OLS). In the present study MCN were obtained from 27
      patients. These MCN were derived from 22 pancreas, three livers, spleen, and
      mesentery. MCN in various organs have common clinicopathological profiles, being
      unilocular or multilocular cystic tumors, with a fibrous capsule and lined by
      mucin-secreting epithelium associated with an underlying subepithelial OLS. The
      OLS showed strong positivity for alpha-smooth muscle actin (alpha-SMA) and
      vimentin and weak, focal positivity for desmin. Both estrogen receptors and
      progesterone receptors were expressed in the nuclei of OLS cells. In addition, 20
      ovarian MCN and 13 normal ovaries were studied with particular attention to the
      stroma. The stroma of ovarian MCN was strongly immunopositive for alpha-SMA and
      vimentin and focally positive for desmin, whereas normal ovarian stroma was
      immunonegative for both alpha-SMA and desmin. The OLS of MCN mentioned here was
      similar to the septa of ovarian MCN but not to ovarian stroma. In conclusion, MCN
      in various organs should be lumped together as 'extra ovarian' MCN. The OLS was
      identified on the basis of myofibroblastic proliferation both in response to
      neoplastic development and dependent on hormones.

PMID- 16445819
TI  - Primary adenoid squamous cell carcinoma of the oral cavity.
AB  - Adenoid squamous cell carcinoma (ASCC) is an uncommon but well-recognized variant
      of squamous cell carcinoma that was first described by Lever in 1947. ASCC has
      been reported to originate in the sun-exposed skin of the head and neck and in
      other sites. An additional case of ASCC is reported here. The patient was a 64
      year-old Japanese woman who requested examination of a reddish lesion on the left
      floor of the mouth. The biopsy material was diagnosed as squamous cell carcinoma.
      Clinical examination showed a well-circumscribed, 20 x 10 mm-sized lesion, which
      was categorized as cT2cN0cm 0. Tumor resection was therefore performed.
      Histologically, most parts of the lesion were conventional squamous cell
      carcinoma in situ, but the invasive part consisted of ASCC with gland-like or
      reticular appearance. The latter part was negative for mucin staining.
      Immunohistochemically, this lesion was positive for pancytokeratin, high
      molecular-weight keratin, cytokeratin (CK) 7/8, CK19, E-cadherin and p53, but
      negative for vimentin, CK20, and S-100 protein. The Ki-67 labeling index was
      50.3% in the ASCC part and 34.5% in the carcinoma in situ part. These findings
      and a review of the literature indicate that a gland-like feature of ASCC is
      associated with the loss of cell adhesion in the center of the cancer nests, and
      it can be confirmed simply by mucin staining to be neither an adenosquamous
      carcinoma nor ductal involvement of conventional squamous cell carcinoma.

PMID- 16445820
TI  - Mixed medullary and follicular cell carcinoma of the thyroid with lymph node
      metastasis in a 7-year-old child.
AB  - A 7-year-old boy presented with midline swelling in the neck. On fine-needle
      aspiration cytology it was diagnosed as papillary carcinoma of the thyroid. The
      patient underwent total thyroidectomy. Histopathological examination,
      immunohistochemistry and electron microscopy revealed the presence of two
      intermingled components: medullary carcinoma and papillary carcinoma. One of the
      submandibular lymph nodes had metastasis of both the components. The case was
      diagnosed as 'mixed medullary and follicular cell carcinoma' with papillary
      carcinoma pattern and lymph node metastasis. Mixed medullary and follicular cell
      carcinoma with intermingling of medullary and papillary carcinoma components is a
      rare tumor. In adults, only eight such cases with lymph node metastasis have been
      published. To the best of the authors' knowledge no pediatric case has previously
      been reported in the English-language literature.

PMID- 16445822
TI  - Female adnexal tumor of probable wolffian origin: morphological,
      immunohistochemical, and ultrastructural study with c-kit gene analysis.
AB  - Female adnexal tumors of probable wolffian origin (FATWO) are rare neoplasms
      believed to originate from mesonephric (wolffian) remnants. Rarity and variable
      location of FATWO make the diagnosis difficult. Although most cases follow a
      benign clinical course, approximately 10% of them either recur or metastasize and
      are thought to be resistant to chemoradiation therapy. In 2004, imatinib therapy,
      a tyrosine kinase inhibitor known to be effective against gastrointestinal
      stromal tumors, was reported to be effective also in a case of KIT-positive
      FATWO. However, c-kit gene mutations in FATWO have never been studied. Herein is
      reported the case of a 50-year-old Japanese woman with FATWO arising in the right
      paratubal site. The tumor had typical characteristics of FATWO in both morphology
      and immunohistochemistry. KIT protein was diffusely and weakly expressed, but DNA
      analysis revealed no mutational change in exon 9 or 11 of the c-kit gene. It is
      believed that accumulation of such genetic data of FATWO are essential from a
      therapeutic standpoint, although the present case had no mutation. In addition,
      the cytological features of this rare tumor are presented, which have not been
      described previously.

PMID- 16445821
TI  - Myxoid variant of adrenocortical carcinoma: report of a unique case.
AB  - Myxoid variant of adrenocortical carcinomas (ACC) are rare, there being only 11
      cases in the literature to date. Reported herein are the findings of a case,
      which in contrast to all previously reported myxoid ACC, was devoid of typical
      non-myxoid areas. The patient was a 61-year-old man in whom a left adrenal mass
      was detected during investigation of Cushing's syndrome. The adrenal was replaced
      by malignant cells and expanses of myxoid material. The cells were positive for
      melan-A, synaptophysin, vimentin and alpha-inhibin. The ultrastructural features
      of the cells were typical of adrenal cortical differentiation. The differential
      diagnosis of myxoid ACC includes extraskeletal myxoid chondrosarcoma, chordoma,
      myxoid adenocarcinoma, myxoma, lipomatous tumors, nerve sheath tumors, smooth
      muscle tumors, gastrointestinal stromal tumor and other sarcomas. The presence of
      myxoid material in a retroperitoneal lesion raises a broad differential diagnosis
      in which myxoid adrenocortical neoplasms should be included. Clinicoradiological
      correlation may be helpful, but special stains, immunohistochemistry and
      ultrastructural examination may be necessary to establish the diagnosis.

PMID- 16445823
TI  - Early recurrence of dense deposit disease with marked endocapillary proliferation
      after renal transplantation.
AB  - Dense deposit disease (DDD), also known as type II membranoproliferative
      glomerulonephritis (MPGN), is characterized by the presence of continuous
      intramembranous dense deposits. At present, the histogenesis of DDD is not well
      known. Reported herein are two cases of early recurrence of DDD in renal
      allografts, with marked endocapillary proliferation. In case 1 the first
      allograft biopsy revealed electron-dense deposits mainly in the subendothelial
      and mesangial areas along with subepithelial humps, but a continuous
      intramembranous deposition was not obvious. In the sequential biopsy, the
      deposits were more often seen in the intramembranous area and finally formed a
      continuous osmiophilic substance, which is a characteristic feature of DDD. In
      case 2, continuous intramembranous deposition already coexisted with
      endocapillary proliferation at the first biopsy. In both cases, endocapillary
      proliferation was alleviated slightly as time progressed. The present report
      suggests that endocapillary proliferative glomerulonephritis is the earliest
      lesion in some cases of DDD. Detailed review of a clinical history and a
      subsequent follow-up biopsy should be done to distinguish these lesions from
      other types of endocapillary proliferative glomerulonephritis.

PMID- 16445824
TI  - T-cell lymphoblastic lymphoma presenting as an intra-muscular mass.

PMID- 16445825
TI  - Unusual abdominal manifestations of catastrophic antiphospholipid syndrome.

PMID- 16445826
TI  - Towards targeted therapy for infant acute lymphoblastic leukaemia.
AB  - Despite the greatly improved treatment regimes for childhood acute lymphoblastic
      leukaemia (ALL) in general, resulting in long-term survival in approximately 80%
      of cases, current therapies still fail in >50% of ALL cases diagnosed within the
      first year of life (i.e. in infants). Therefore, more adequate treatment
      strategies are urgently needed to also improve the prognosis for these very young
      patients with ALL. Here we review the current acquaintance with the biology of
      infant ALL and describe how this knowledge may lead to innovative therapeutic
      approaches.

PMID- 16445827
TI  - Obtaining consent for chemotherapy.

PMID- 16445828
TI  - cFLIP expression correlates with tumour progression and patient outcome in non
      Hodgkin lymphomas of low grade of malignancy.
AB  - The present study investigated whether the expression of cellular Fas-associated
      death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein
      (cFLIP) conveys prognostic information in non-Hodgkin lymphomas (NHLs). cFLIP
      expression was quantified by immunohistochemistry and immunofluorescence in
      biopsy specimens from 86 NHL patients for whom clinical information was
      available. NHL malignancy was graded as high/intermediate or low according to the
      World Health Organization Classification of Lymphoid Neoplasms. cFLIP was
      positive in 23 of 45 high-/intermediate-grade NHLs and in 25 of 41 low-grade
      NHLs. Negative expression of cFLIP was associated with the presence of apoptotic
      cells in the tumour mass, regardless of the histotype and of the malignancy
      grade. In NHLs positive for cFLIP, 11 of 23 (48%) high-/intermediate-grade cases
      and 18 of 25 (72%) low-grade cases showed a bad outcome. In NHLs negative for
      cFLIP, only four of 22 (18%) high-/intermediate-grade patients and 12 of 16 (75%)
      low-grade patients achieved complete remission. All these correlations were
      statistically significant. The correlation of cFLIP expression with clinical
      outcome was independent of therapy, whether or not it included anti-CD20 antibody
      (Rituximab). The present findings strongly indicate that cFLIP is a reliable
      predictor of tumour progression and clinical prognosis in NHLs of low grade of
      malignancy.

PMID- 16445829
TI  - Analysis of immunoglobulin V genes suggests cutaneous marginal zone B-cell
      lymphomas recognise similar antigens.
AB  - Extranodal marginal zone B-cell lymphomas (EMZL) are thought to develop from
      reactive infiltrates that represent immune responses to external or auto
      antigens. Except for gastric EMZL, the antigenic triggers of EMZL development are
      mostly unknown, although a subset of cutaneous EMZL have been associated with
      Borrelia burgdorferi infections. To further evaluate whether a common antigen may
      be promoting the development of cutaneous EMZL, the immunoglobulin heavy chain
      variable (V(H)) genes from eight USA cases were sequenced and analysed. All used
      V(H)3 family gene segments, with 2/8 using the same V3-30 segment, 2/8 using the
      closely related V3-30.3 or V3-33 segments, 6/8 containing mutations and 2/7
      showing evidence of ongoing mutation. Many of the complimentarity-determining
      region 3s (CDR3s) also showed similarities in length and displayed conserved
      amino acid motifs in the non-templated areas between the diversity and joining
      segments. The use of similar V(H) gene segments and conserved CDR3 amino acid
      motifs suggests that some of these cutaneous EMZL may bind the same or similar
      antigen via their surface immunoglobulin receptor. Analysis of the somatic
      mutations present in many of the V(H) genes was also consistent with antigen
      directly stimulating the growth of cutaneous EMZL.

PMID- 16445830
TI  - Treatment for myeloid leukaemia of Down syndrome: population-based experience in
      the UK and results from the Medical Research Council AML 10 and AML 12 trials.
AB  - Down syndrome (DS) children are at an increased risk of developing myelodysplasia
      and acute myeloid leukaemia (AML). We retrospectively analysed the population
      based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from
      the UK National Registry of Childhood Tumours and experience in the Medical
      Research Council (MRC) AML 10 and AML 12 trials, which enrolled 46 children with
      ML-DS from 1988 to 2002. Eight per cent of UK children with AML had DS, but DS
      children comprised only 5% of children registered in MRC trials. The unique
      clinical characteristics of ML-DS were confirmed. Overall survival (OS) of ML-DS
      at 5 years increased from 47% in UK children diagnosed from 1988 to 1995 to 75%
      in children diagnosed from 1996 to 2002. OS for DS children registered in AML 10
      and AML 12 was 74% in 5 years and improved from AML 10 to AML 12 (56% vs. 83%)
      There was no significant difference in OS between DS and non-DS children (OS: 74%
      vs. 62%, P = 0.4) in the trials, but this result masked a significant increase in
      early death amongst DS children, with a significant reduction in mortality later
      on. Relapse was significantly reduced (3% vs. 39%, P = 0.0003), leading to the
      improved disease-free survival (83% vs. 56%, P = 0.02). Given the increased
      number of early treatment-related deaths, future treatment protocols should aim
      to reduce chemotherapy dosage or intensity whilst maintaining low rates of
      resistant and recurrent disease.

PMID- 16445831
TI  - A systematic review of phase-II trials of thalidomide monotherapy in patients
      with relapsed or refractory multiple myeloma.
AB  - The activity of thalidomide in relapsed or refractory multiple myeloma is widely
      accepted but not yet demonstrated in a randomised-controlled trial. A systematic
      review of the published clinical trials of these patients could reduce the
      possible bias of single phase-II studies. A systematic search identified 42
      communications reporting on 1674 patients. Thirty-two trials used an escalating
      dosing regimen and four a fixed dose regimen (one dose with 50 mg/d, three doses
      with 200 mg/d). The target dose in the dose escalating trials was 800 mg/d in 17
      trials, 400-600 mg/d in 10 and 200 mg/d in one trial. The intention-to-treat
      population for efficacy was 1629 patients with a median age of 62 years. The
      complete and partial (>50% reduction in monoclonal protein) response rate was
      29.4% (95%-confidence interval, 27-32%). The rates for minor responses or stable
      disease were 13.8% (12-16%) and 11.0% (9-13%). Progressive disease was reported
      in 9.9% (8-11%). The median overall survival from all trials was reported at 14
      months. Severe adverse events (grade III-IV) included somnolence 11%,
      constipation 16%, neuropathy 6%, rash 3%, thrombo-embolism 3%, cardiac 2%. In
      conclusion, thalidomide monotherapy achieved complete and partial responses in
      29.4% of patients with relapsed or refractory multiple myeloma.

PMID- 16445832
TI  - Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of
      registered cases in Japan.
AB  - This report presents a retrospective study of 26 Japanese children with recurrent
      anaplastic large cell lymphoma. The first relapses were documented at a median of
      10.5 months after the initial diagnosis. Twenty-four patients achieved a second
      remission. After a median follow-up period of 47 months, 18 patients are still
      alive: 15 patients are in second complete remission (CR), three patients are in
      third CR or later. The 5 year overall and relapse-free survival rates were 61 +/-
      12% and 51 +/- 12% respectively. The patients who received allogeneic
      haematopoietic stem cell transplantation during second CR showed a superior
      outcome to other patients.

PMID- 16445833
TI  - A randomised control trial of patient self-management of oral anticoagulation
      compared with patient self-testing.
AB  - Several studies suggest that patient self-management (PSM) may improve the
      quality of oral anticoagulation therapy as measured by time spent within the
      international normalised ratio (INR) target range. We performed a prospective
      randomised control trial to determine whether the improvement in quality of
      treatment afforded by PSM is greater than that achieved by patient self-testing
      (PST) alone. A total of 104 of 800 eligible patients aged 22-88 years (median =
      59.8), attending our hospital anticoagulant clinic and receiving long-term
      warfarin for >8 months agreed to participate. Patients were randomised to PSM (n
      = 55) or PST (n = 49). Both groups measured their INR using the CoaguChek S every
      2 weeks or more frequently if required, for a period of 6 months. Seventy-seven
      of 104 (74%) patients completed the study (PSM = 41 and PST = 36). The 'drop out'
      rates for both groups were similar. There was no significant difference between
      the percentage time in target therapeutic range for PSM (69.9%) and PST (71.8%).
      Both groups combined showed a significant improvement over the previous 6 months
      (71.0% vs. 62.5%; P = 0.04). Changes in time within the therapeutic range in
      individual patients (+5.86) also showed a significant difference. The quality of
      warfarin control in both PST and PSM may be superior to that achieved by
      conventional management in a specialised hospital anticoagulation clinic.

PMID- 16445835
TI  - Correction of severe anaemia using immuno-regulated gene therapy is achieved by
      restoring the early erythroblast compartment.
AB  - Patients with chronic renal failure usually require exogenous erythropoietin
      (epo) to alleviate anaemia resulting from inadequate epo production by the
      kidneys. We have recently shown that severe anaemia in genetically manipulated
      epo-deficient mice (EpoTAg) can be corrected by adoptively transferred epo
      producing lymphocytes. The aim of this study was to investigate the precise
      effects of human epo administration by this route on erythropoietic development
      in epo-deficient mice. The erythroblast compartments of untreated and treated
      EpoTAg mice were analysed in comparison with wild-type mice. The early
      erythroblast population was reduced in the bone marrow of epo-deficient mice,
      whilst the number of erythroid colony-forming units (CFU-E) was not significantly
      compromised. This paucity in marrow early erythroblasts was restored to normal
      values in treated mutant mice. In addition, the early erythroblast population was
      expanded in the spleens of treated animals. These findings show that the early
      erythroblasts are important targets of epo and that epo corrects anaemia of epo
      deficient mice by restoring marrow function and splenic erythropoiesis.

PMID- 16445834
TI  - Poor correlation of supratherapeutic international normalised ratio and vitamin K
      dependent procoagulant factor levels during warfarin therapy.
AB  - Patients with a supratherapeutic international normalised ratio (ST-INR) are at
      risk for bleeding. ST-INR is corrected by withholding warfarin therapy and often
      by supplementing vitamin K or providing vitamin K-dependent factors; the exact
      therapeutic decision is based on the extent of the prolonged INR. Currently, ST
      INRs are frequently observed in clinical practice due to the use of sensitive
      recombinant tissue thromboplastin reagents and automation. However, there are
      scant data correlating an ST-INR with various vitamin K-dependent factors. This
      prospective cohort study, set in a large tertiary care teaching hospital for the
      University of Texas Southwestern Medical Center at Dallas, defined the
      relationship between ST-INR (>5.0) and measured vitamin K-dependent procoagulant
      factors. Prothrombin time, INR and vitamin K-dependent factors II, VII, IX and X
      were measured in 78 patients with an INR > 5.0 (ST-INR) who were on warfarin
      therapy for more than 2 months. There was no significant relationship between the
      ST-INR and levels of important vitamin K-dependent factors II and X. These data
      support the recent guidelines that the management of an INR > 5.0 should be
      driven by the clinical determinants rather than specific INR values per se.

PMID- 16445836
TI  - Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating,
      G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.
AB  - Natural products are still an untapped source of promising lead compounds for the
      generation of antineoplastic drugs. Here, we investigated for the first time the
      antiproliferative and apoptotic effects of highly purified oxindole alkaloids,
      namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F
      (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American
      Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the
      five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia
      cells. Furthermore, the antiproliferative effect of the most potent alkaloids
      pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis.
      After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2
      sublines with tetracycline-regulated expression of bcl-2, p16ink4A or
      constitutively expressing the cowpox virus protein crm-A were used for further
      studies of the apoptosis-inducing properties of these alkaloids. Neither
      overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by
      tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced
      apoptosis. Our results show the strong apoptotic effects of pteropodine and
      uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for
      further studies in xenograft models.

PMID- 16445837
TI  - Cellular folate vitamer distribution during and after correction of vitamin B12
      deficiency: a case for the methylfolate trap.
AB  - Haematological sequellae of vitamin B12 deficiency are attributed to disturbed
      DNA synthesis, but vitamin B12 itself plays no role in DNA biosynthesis. A
      proposed explanation for this is the methylfolate trap hypothesis. This
      hypothesis states that B12 deficiency impairs overall folate metabolism because 5
      methyltetrahydrofolate (5MTHF) becomes metabolically trapped. This trap results
      from the fact that 5MTHF can neither be metabolised via the methionine synthase
      pathway, nor can it be reconverted to its precursor, methylenetetrahydrofolate.
      Other manifestations of the methylfolate trap include cellular folate loss
      because of shorter 5MTHF polyglutamate chains and global hypomethylation. The
      methylfolate trap has never been demonstrated in humans. We describe a patient
      with B12 deficiency who was homozygous for the common methylenetetrahydrofolate
      reductase (MTHFR) C677T mutation. We analysed red blood cell (RBC) folate
      vitamers and global DNA methylation by liquid chromatography (LC) in combination
      with tandem mass spectrometry, and 5MTHF polyglutamate length by LC
      electrochemical detection. Compared to post-B12 supplementation values,
      homocysteine was higher (52.9 micromol/l vs. 16.8 micromol/l), RBC folate was
      lower (268.92 nmol/l vs. 501.2 nmol/l), the 5MTHF fraction of RBC folate was much
      higher (94.5% vs. 67.4%), polyglutamate chain length was shorter (more tetra- and
      pentaglutamates), and global DNA methylation was 22% lower. This is the first
      time that virtually all features of the methylfolate trap hypothesis have been
      demonstrated in a human with vitamin B12 deficiency.

PMID- 16445838
TI  - Myeloid lineage-selective growth of revertant cells in Fanconi anaemia.
AB  - Fanconi anaemia (FA) is a genetically heterogeneous chromosome instability
      syndrome characterised by bone marrow failure and congenital anomalies. Although
      an increasing number of reports suggest that reversion mosaicism noted in
      peripheral blood lymphocytes (PBLs) is associated with mild haematopoietic
      failure in FA, myeloid cells are rarely directly examined. We here report a
      patient with prolonged mild pancytopenia in whom proliferation of revertant cells
      was detected in mature myeloid cells but not in PBLs. While this patient had
      inherited heterozygous mutations, 2546delC and 3720-3724del, in the major FA gene
      FANCA, Epstein-Barr virus-immortalised lymphoblastoid cells from the patient had
      2546C > T instead of 2546delC, resulting in expression of a functional missense
      protein. As the identical reversion was detected in polymorphonuclear
      granulocytes and mononuclear phagocytes, sustained haematopoiesis in the patient
      can be attributed to a selective growth advantage of revertant myeloid cells. It
      is noteworthy that such a myeloid lineage-selective mosaicism is overlooked in
      routine examination of PBLs. Recognition of this status will expand the role of
      reversion mosaicism in the pathophysiology of FA.

PMID- 16445839
TI  - Increased levels of soluble flt-3 ligand in serum and long-term bone marrow
      culture supernatants in patients with chronic idiopathic neutropenia.
AB  - The levels of serum and long-term bone marrow culture supernatant soluble flt-3
      ligand (sFL) were determined in 54 patients with chronic idiopathic neutropenia
      (CIN) and 16 normal controls. Both serum and supernatant sFL levels were
      significantly increased in the patients compared with controls. Individual sFL
      values inversely correlated with the number of circulating neutrophils and the
      proportion of bone marrow CD34+ cells. Supernatant sFL values positively
      correlated with the levels of supernatant G-CSF. These findings suggest that the
      impaired myelopoiesis in CIN patients is accompanied by a compensatory mechanism
      attempting to increase the neutrophil production at the myeloid progenitor cell
      level.

PMID- 16445840
TI  - Thalassaemia-like carriers not linked to the beta-globin gene cluster.
AB  - This study describes the largest series reported to date, of individuals
      belonging to unrelated families carrying a beta-thalassaemia-like phenotype in
      whom the beta-globin gene was found to be structurally intact by sequence
      analysis. This genetic determinant appears haematologically heterogeneous,
      displaying either a silent beta-thalassaemia-like phenotype or a typical beta
      thalassaemia carrier-like phenotype in different families. Compound
      heterozygosity for both beta-thalassaemia-like determinant and typical beta
      thalassaemia allele resulted either in thalassaemia intermedia or thalassaemia
      major. By linkage analysis both the silent and the typical beta-like determinants
      were found not to be linked to the beta-globin cluster. Sequence analysis of the
      hypersensitive site cores of locus control region and of the genes coding for the
      transcription factors erythroid Kruppel-like factor and nuclear factor (erythroid
      derived 2) were normal. beta-globin mRNA levels determined by real-time
      polymerase chain reaction were reduced in both types of beta-like carriers. These
      results indicate the existence of causative genetic determinants not yet
      molecularly defined, but most likely, resulting from either the reduction or loss
      of function of a gene coding for unknown transcriptional regulator(s) of the beta
      globin gene. The knowledge of these rare beta-thalassaemia-like determinants have
      implications for clinical and, especially, prenatal diagnosis of beta
      thalassaemia.

PMID- 16445841
TI  - Absence of Chlamydia psittaci in ocular adnexal lymphoma from Japanese patients.

PMID- 16445842
TI  - Inconsistencies in the association between the JAK2(V617F) mutation and PRV-1
      over-expression among the chronic myeloproliferative diseases.

PMID- 16445844
TI  - Does a negative direct antiglobulin test exclude warm autoimmune haemolytic
      anaemia? A prospective study of 504 cases.

PMID- 16445845
TI  - In meta-analysis itraconazole is superior to fluconazole for prophylaxis of
      systemic fungal infection in the treatment of haematological malignancy.

PMID- 16445847
TI  - Mediterranean stomatocytosis/macrothrombocytopenia: update from Adelaide,
      Australia.

PMID- 16445853
TI  - Involvement of organic anion transporters in the efflux of uremic toxins across
      the blood-brain barrier.
AB  - Renal failure causes multiple physiological changes involving CNS dysfunction. In
      cases of uremia, there is close correlation between plasma levels of uremic
      toxins [e.g. 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), hippurate (HA)
      and indoleacetate (IA)] and the degree of uremic encephalopathy, suggesting that
      uremic toxins are involved in uremic encephalopathy. In order to evaluate the
      relevance of uremic toxins to CNS dysfunction, we investigated directional
      transport of uremic toxins across the blood-brain barrier (BBB) using in vivo
      integration plot analysis and the brain efflux index method. We observed
      saturable efflux transport of [(3)H]CMPF, [(14)C]HA and [(3)H]IA, which was
      inhibited by probenecid. For all uremic toxins evaluated, apparent efflux
      clearance across the BBB was greater than apparent influx clearance, suggesting
      that these toxins are predominantly transported from the brain to blood across
      the BBB. Saturable efflux transport of [(3)H]CMPF, [(14)C]HA and [(3)H]IA was
      completely inhibited by benzylpenicillin, which is a substrate of rat organic
      anion transporter 3 (rOat3). Taurocholate and digoxin, which are common
      substrates of rat organic anion transporting polypeptide (rOatp), partially
      inhibited the efflux of [(3)H]CMPF. Transport experiments using a Xenopus laevis
      oocyte expression system revealed that CMPF, HA and IA are substrates of rOat3,
      and that CMPF (but not HA or IA) is a substrate of rOap2. These results suggest
      that rOat3 mediates brain-to-blood transport of uremic toxins, and that rOatp2 is
      involved in efflux of CMPF. Thus, conditions typical of uremia can cause
      inhibition of brain-to-blood transport involving rOat3 and/or rOatp2, leading to
      accumulation of endogenous metabolites and drugs in the brain.

PMID- 16445852
TI  - Expression of arginine decarboxylase in brain regions and neuronal cells.
AB  - After our initial report of a mammalian gene for arginine decarboxylase, an
      enzyme for the synthesis of agmatine from arginine, we have determined the
      regional expression of ADC in rat. We have analyzed the expression of ADC in rat
      brain regions by activity, protein and mRNA levels, and the regulation of
      expression in neuronal cells by RNA interference. In rat brain, ADC was widely
      expressed in major brain regions, with a substantial amount in hypothalamus,
      followed by cortex, and with least amounts in locus coeruleus and medulla. ADC
      mRNA was detected in primary astrocytes and C6 glioma cells. While no ADC message
      was detected in fresh neurons (3 days old), significant message appeared in
      differentiated neurons (3 weeks old). PC12 cells, treated with nerve growth
      factor, had higher ADC mRNA compared with naive cells. The siRNA mixture directed
      towards the N-terminal regions of ADC cDNA down-regulated the levels of mRNA and
      protein in cultured neurons/C6 glioma cells and these cells produced lower
      agmatine. Thus, this study demonstrates that ADC message is expressed in rat
      brain regions, that it is regulated in neuronal cells and that the down
      regulation of ADC activity by specific siRNA leads to lower agmatine production.

PMID- 16445854
TI  - Ectopic expression of tyrosine hydroxylase in the pigmented epithelium rescues
      the retinal abnormalities and visual function common in albinos in the absence of
      melanin.
AB  - Albino mammals have profound retinal abnormalities, including photoreceptor
      deficits and misrouted hemispheric pathways into the brain, demonstrating that
      melanin or its precursors are required for normal retinal development.
      Tyrosinase, the primary enzyme in melanin synthesis commonly mutated in albinism,
      oxidizes l-tyrosine to l-dopaquinone using l-3,4-dihydroxyphenylalanine (L-DOPA)
      as an intermediate product. L-DOPA is known to signal cell cycle exit during
      retinal development and plays an important role in the regulation of retinal
      development. Here, we have mimicked L-DOPA production by ectopically expressing
      tyrosine hydroxylase in mouse albino retinal pigment epithelium cells. Tyrosine
      hydroxylase can only oxidize l-tyrosine to L-DOPA without further progression
      towards melanin. The resulting transgenic animals remain phenotypically albino,
      but their visual abnormalities are corrected, with normal photoreceptor numbers
      and hemispheric pathways and improved visual function, assessed by an increase of
      spatial acuity. Our results demonstrate definitively that only early melanin
      precursors, L-DOPA or its metabolic derivatives, are vital in the appropriate
      development of mammalian retinae. They further highlight the value of
      substituting independent but biochemically related enzymes to overcome
      developmental abnormalities.

PMID- 16445855
TI  - Roles and practices of general practitioners and psychiatrists in management of
      depression in the community.
AB  - BACKGROUND: Little is known about depressed patients' profiles and how they are
      managed. The aim of the study is to compare GPs and psychiatrists for 1 degrees)
      sociodemographic and clinical profile of their patients considered as depressed 2
      degrees) patterns of care provision. METHODS: The study design is an
      observational cross-sectional study on a random sample of GPs and psychiatrists
      working in France. Consecutive inclusion of patients seen in consultation
      considered as depressed by the physician. GPs enrolled 6,104 and psychiatrists
      1,433 patients. DATA COLLECTED: sociodemographics, psychiatric profile,
      environmental risk factors of depression and treatment. All clinical data were
      collected by participating physicians; there was no direct independent clinical
      assessment of patients to check the diagnosis of depressive disorder. RESULTS:
      Compared to patients identified as depressed by GPs, those identified by
      psychiatrists were younger, more often urban (10.5% v 5.4% - OR = 2.4), educated
      (42.4% v 25.4% - OR = 3.9), met DSM-IV criteria for depression (94.6% v 85.6% -
      OR = 2.9), had been hospitalized for depression (26.1% v 15.6% - OR = 2.0) and
      were younger at onset of depressive problems (all adjusted p < .001). No
      difference was found for psychiatric and somatic comorbidity, suicide attempt and
      severity of current depression. Compared to GPs, psychiatrists more often
      prescribed tricyclics and very novel antidepressants (7.8% v 2.3% OR = 5.0 and
      6.8% v 3.0% OR = 3.8) with longer duration of antidepressant treatment. GPs'
      patients received more "non-conventional" treatment (8.8% v 2.4% OR = 0.3) and
      less psychotherapy (72.2% v 89.1% OR = 3.1) (all adjusted p < .001). CONCLUSION:
      Differences between patients mainly concerned educational level and area of
      residence with few differences regarding clinical profile. Differences between
      practices of GPs and psychiatrists appear to reflect more the organization of the
      French care system than the competence of providers.

PMID- 16445856
TI  - Correlation between the presence of neutralizing antibodies against porcine
      circovirus 2 (PCV2) and protection against replication of the virus and
      development of PCV2-associated disease.
AB  - BACKGROUND: In a previous study, it was demonstrated that high replication of
      Porcine circovirus 2 (PCV2) in a gnotobiotic pig was correlated with the absence
      of PCV2-neutralizing antibodies. The aim of the present study was to investigate
      if this correlation could also be found in SPF pigs in which PMWS was
      experimentally reproduced and in naturally PMWS-affected pigs. RESULTS: When
      looking at the total anti-PCV2 antibody titres, PMWS-affected and healthy animals
      seroconverted at the same time point, and titres in PMWS-affected animals were
      only slightly lower compared to those in healthy animals. In healthy animals, the
      evolution of PCV2-neutralizing antibodies coincided with that of total
      antibodies. In PMWS-affected animals, neutralizing antibodies could either not be
      found (sera from field studies) or were detected in low titres between 7 and 14
      DPI only (sera from experimentally inoculated SPF pigs). Differences were also
      found in the evolution of specific antibody isotypes titres against PCV2. In
      healthy pigs, IgM antibodies persisted until the end of the study, whereas in
      PMWS-affected pigs they quickly decreased or remained present at low titres. The
      mean titres of other antibody isotypes (IgG1, IgG2 and IgA), were slightly lower
      in PMWS-affected pigs compared to their healthy group mates at the end of each
      study. CONCLUSION: This study describes important differences in the development
      of the humoral immune response between pigs that get subclinically infected with
      PCV2 and pigs that experience a high level of PCV2-replication which in 3 of 4
      experiments led to the development of PMWS. These observations may contribute to
      a better understanding of the pathogenesis of a PCV2-infection.

PMID- 16445857
TI  - S. pneumoniae transmission according to inclusion in conjugate vaccines: Bayesian
      analysis of a longitudinal follow-up in schools.
AB  - BACKGROUND: Recent trends of pneumococcal colonization in the United States,
      following the introduction of conjugate vaccination, indicate that non-vaccine
      serotypes tend to replace vaccine serotypes. The eventual extent of this
      replacement is however unknown and depends on serotype-specific carriage and
      transmission characteristics. METHODS: Here, some of these characteristics were
      estimated for vaccine and non-vaccine serotypes from the follow-up of 4,488
      schoolchildren in France in 2000. A Bayesian approach using Markov chain Monte
      Carlo data augmentation techniques was used for estimation. RESULTS: Vaccine and
      non-vaccine serotypes were found to have similar characteristics: the mean
      duration of carriage was 23 days (95% credible interval (CI): 21, 25 days) for
      vaccine serotypes and 22 days (95% CI: 20, 24 days) for non-vaccine serotypes;
      within a school of size 100, the Secondary Attack Rate was 1.1% (95% CI: 1.0%,
      1.2%) for both vaccine and non-vaccine serotypes. CONCLUSION: This study supports
      that, in 3-6 years old children, no competitive advantage exists for vaccine
      serotypes compared to non-vaccine serotypes. This is an argument in favour of
      important serotype replacement. It would be important to validate the result for
      infants, who are known to be the main reservoir in maintaining transmission.
      Overall reduction in pathogenicity should also be taken into account in
      forecasting the future burden of pneumococcal colonization in vaccinated
      populations.

PMID- 16445859
TI  - Stable silencing of SNAP-25 in PC12 cells by RNA interference.
AB  - BACKGROUND: SNAP-25 is a synaptic protein known to be involved in exocytosis of
      synaptic vesicles in neurons and of large dense-core vesicles in neuroendocrine
      cells. Its role in exocytosis has been studied in SNAP-25 knockout mice, in lysed
      synaptosomes lacking functional SNAP-25 and in cells after treatment with
      botulinum toxins A or E that specifically cleave SNAP-25. These studies have
      shown that SNAP-25 appears to be required for most but not all evoked secretion.
      In order to further study the role of SNAP-25 in catecholamine secretion from
      PC12 cells we have used the recently developed technique of RNA interference to
      generate PC12 cell lines with virtually undetectable levels of SNAP-25. RNA
      interference is the sequence-specific silencing or knockdown of gene expression
      triggered by the introduction of double-stranded RNA into a cell. RNA
      interference can be elicited in mammalian cells in a number of ways, one of which
      is by the expression of small hairpin RNAs from a transfected plasmid. Selection
      of stably transfected cell lines expressing a small hairpin RNA allows one-time
      characterization of the degree and specificity of gene silencing and affords a
      continuing source of well-characterized knockdown cells for experimentation.
      RESULTS: A PC12 cell line stably transfected with a plasmid expressing an shRNA
      targeting SNAP-25 has been established. This SNAP-25 knockdown cell line has
      barely detectable levels of SNAP-25, but normal levels of other synaptic
      proteins. Catecholamine secretion elicited by depolarization of the SNAP-25
      knockdown cells was reduced to 37% of control. CONCLUSION: Knockdown of SNAP-25
      in PC12 cells reduces but does not eliminate evoked secretion of catecholamines.
      Transient expression of human SNAP-25 in the knockdown cells rescues the deficit
      in catecholamine secretion.

PMID- 16445858
TI  - Identification of mitogen-activated protein kinase docking sites in enzymes that
      metabolize phosphatidylinositols and inositol phosphates.
AB  - BACKGROUND: Reversible interactions between the components of cellular signaling
      pathways allow for the formation and dissociation of multimolecular complexes
      with spatial and temporal resolution and, thus, are an important means of
      integrating multiple signals into a coordinated cellular response. Several
      mechanisms that underlie these interactions have been identified, including the
      recognition of specific docking sites, termed a D-domain and FXFP motif, on
      proteins that bind mitogen-activated protein kinases (MAPKs). We recently found
      that phosphatidylinositol-specific phospholipase C-gamma1 (PLC-gamma1) directly
      binds to extracellular signal-regulated kinase 2 (ERK2), a MAPK, via a D-domain
      dependent mechanism. In addition, we identified D-domain sequences in several
      other PLC isozymes. In the present studies we sought to determine whether MAPK
      docking sequences could be recognized in other enzymes that metabolize
      phosphatidylinositols (PIs), as well as in enzymes that metabolize inositol
      phosphates (IPs). RESULTS: We found that several, but not all, of these enzymes
      contain identifiable D-domain sequences. Further, we found a high degree of
      conservation of these sequences and their location in human and mouse proteins;
      notable exceptions were PI 3-kinase C2-gamma, PI 4-kinase type IIbeta, and
      inositol polyphosphate 1-phosphatase. CONCLUSION: The results indicate that there
      may be extensive crosstalk between MAPK signaling and signaling pathways that are
      regulated by cellular levels of PIs or IPs.

PMID- 16445861
TI  - Y chromosome microdeletions in infertile men with idiopathic oligo- or
      azoospermia.
AB  - About 30-40% of male infertility is due to unknown reasons. Genetic contributions
      to the disruption of spermatogenesis are suggested and amongst the genetic
      factors studied, Y chromosome microdeletions represent the most common one.
      Screening for microdeletions in AZFa, b and c region of Y chromosome showed a big
      variation among different studies. The purpose of this study was to investigate
      the prevalence of such deletions in Saudi men. A total of 257 patients with
      idiopathic oligo- or azoospermia were screened for Y chromosome microdeletions by
      19 markers in AZF region. Ten (3.9%) patients had chromosomal rearrangements, six
      of them showed sex chromosome abnormalities and four patients had apparently
      balanced autosomal rearrangements. Eight of the remaining 247 patients (3.2%)
      with a normal karyotype and no known causes of impaired spermatogenesis had Y
      chromosome microdeletions. Among these, six patients had deletions in AZFc
      region, one case had a deletion in AZFb and another had both AZFa and AZFc
      deletions.In conclusion, our study shows that Y chromosome microdeletions are low
      in our population. We also report for the first time a case with unique point
      deletions of AZFa and AZFc regions. The lower frequency of deletions in our study
      suggest that other genetic, epigenetic, nutritional and local factors may be
      responsible for idiopathic oligo- or azoospermia in the Saudi population.

PMID- 16445860
TI  - Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses and
      syphilis infections among blood donors at the Muhimbili National Hospital in Dar
      es Salaam, Tanzania.
AB  - BACKGROUND: According to the latest Tanzanian National AIDS Control Programme
      (NACP) report a total of 147,271 individuals donated blood during the year 2002.
      However, blood safety remains an issue of major concern in transfusion medicine
      in Tanzania where national blood transfusion services and policies, appropriate
      infrastructure, trained personnel and financial resources are inadequate. Most of
      the donated blood is screened for HIV alone. METHODS: We determined among blood
      donors at Muhimbili National Hospital (MNH), the seroprevalence of human
      immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface
      antigen (HBsAg) and syphilis by donor type, sex and age and to determine
      association, if any, in the occurrence of the pathogens. The sample included 1599
      consecutive donors, 1424(89.1%) males and 175 (10.9%) females, who donated blood
      between April 2004 and May, 2005. Most of them 1125 (70.4%) were replacement
      donors and a few 474 (29.6%) voluntary donors. Their age (in years) ranged from
      16 to 69, and most (72.2%) were between 20-39 years. RESULTS: Two hundred and
      fifty four (15.9%) of the donated blood had serological evidence of infection
      with at least one pathogen and 28 (1.8%) had multiple infections. The current
      seroprevalence of HIV, HBsAg, HCV and syphilis among blood donors at MNH in Dar
      es Salaam was found to be 3.8%, 8.8%, 1.5% and 4.7%, respectively. Respective
      seroprevalences among HIV seronegative blood donors were 8.7% for HBV, 1.6% for
      HCV and 4.6% for syphilis. The differences in the prevalence of HIV and syphilis
      infections between replacement and voluntary donors were statistically
      significant (P < 0.05). Syphilis was the only infection that occurred more
      frequently among HIV infected (12.1%) than non-infected (4.6%) blood donors (P <
      0.05), and whose prevalence increased with age (X2 = 58.5 df = 5, P < 0.001).
      There were no significant sex differences in the occurrence of pathogens.
      Finally, there were significant associations in the occurrence of HBsAg and
      syphilis (OR = 2.2, 95% CI 1.1.-4.2) and HIV and syphilis (OR = 2.2, 95% CI 1.0
      5.3). CONCLUSION: The high (15.9%) seroprevalence of blood-borne infections in
      blood donated at MNH calls for routine screening of blood donors for HBV, HCV,
      HIV and syphilis and for strict selection criteria of donors, with emphasis on
      getting young voluntary donors and for establishment of strict guidelines for
      blood transfusions.

PMID- 16445862
TI  - Intrathecal long-term gene expression by self-complementary adeno-associated
      virus type 1 suitable for chronic pain studies in rats.
AB  - BACKGROUND: Intrathecal (IT) gene transfer is an attractive approach for
      targeting spinal mechanisms of nociception but the duration of gene expression
      achieved by reported methods is short (up to two weeks) impairing their utility
      in the chronic pain setting. The overall goal of this study was to develop IT
      gene transfer yielding true long-term transgene expression defined as > or = 3 mo
      following a single vector administration. We defined "IT" administration as
      atraumatic injection into the lumbar cerebrospinal fluid (CSF) modeling a lumbar
      puncture. Our studies focused on recombinant adeno-associated virus (rAAV), one
      of the most promising vector types for clinical use. RESULTS: Conventional single
      stranded rAAV2 vectors performed poorly after IT delivery in rats. Pseudotyping
      of rAAV with capsids of serotypes 1, 3, and 5 was tested alone or in combination
      with a modification of the inverted terminal repeat. The former alters vector
      tropism and the latter allows packaging of self-complementary rAAV (sc-rAAV)
      vectors. Combining both types of modification led to the identification of sc
      rAAV2/l as a vector that performed superiorly in the IT space. IT delivery of 3 x
      10e9 sc-rAAV2/l particles per animal led to stable expression of enhanced green
      fluorescent protein (EGFP) for > or = 3 mo detectable by Western blotting,
      quantitative PCR, and in a blinded study by confocal microscopy. Expression was
      strongest in the cauda equina and the lower sections of the spinal cord and only
      minimal in the forebrain. Microscopic examination of the SC fixed in situ with
      intact nerve roots and meninges revealed strong EGFP fluorescence in the nerve
      roots. CONCLUSION: sc-rAAVl mediates stable IT transgene expression for > or = 3
      mo. Our findings support the underlying hypothesis that IT target cells for gene
      transfer lack the machinery for efficient conversion of the single-stranded rAAV
      genome into double-stranded DNA and favor uptake of serotype 1 vectors over 2.
      Experiments presented here will provide a rational basis for utilizing IT rAAV
      gene transfer in basic and translational studies on chronic pain.

PMID- 16445863
TI  - RNAi dependent epigenetic marks on a geminivirus promoter.
AB  - Nicotiana benthamiana plants were stably transformed with an intron-spliced dsRNA
      producing construct cognate to bidirectional promoter of African cassava mosaic
      geminivirus (ACMV) DNA A. Transgenic lines expressed multiple siRNAs species upon
      ACMV infection. The de novo DNA methylation and an increased proportion of
      histone H3 Lysine-9 methylation (H3K9) at intergenic region (IGR) of ACMV DNA A
      were observed.

PMID- 16445864
TI  - Intercellular adhesion molecule-1 expression in human endometrium: implications
      for long term progestin only contraception.
AB  - BACKGROUND: Neutrophils infiltrate the endometrium pre-menstrually and after long
      term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils
      involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1).
      Previous studies observed that ICAM-1 was immunolocalized to the endothelium of
      endometrial specimens across the menstrual cycle, but disagreed as to whether
      extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies
      across the menstrual cycle. METHODS: Endometrial biopsies were obtained from
      women across the menstrual cycle and from those on LTPOC treatment (either Mirena
      or Norplant). The biopsies were formalin-fixed and paraffin-embedded with
      subsequent immunohistochemical staining for ICAM-1. RESULTS: The current study
      found prominent ICAM-1 staining in the endometrial endothelium that was of
      equivalent intensity in different blood vessel types irrespective of the
      steroidal or inflammatory endometrial milieu across the menstrual cycle and
      during LTPOC therapy. Unlike the endothelial cells, the glands were negative and
      the stromal cells were weakly positive for ICAM immunostaining. CONCLUSION: The
      results of the current study suggest that altered expression of ICAM-1 by
      endothelial cells does not account for the influx of neutrophils into the
      premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may
      depend on altered expression of neutrophil chemoattractants.

PMID- 16445865
TI  - Use of carbon-13 as a population marker for Anopheles arabiensis in a sterile
      insect technique (SIT) context.
AB  - BACKGROUND: Monitoring of sterile to wild insect ratios in field populations can
      be useful to follow the progress in genetic control programmes such as the
      Sterile Insect Technique (SIT). Of the numerous methods for marking insects most
      are not suitable for use in mass rearing and mass release. Suitable ones include
      dye marking, genetic marking and chemical marking. METHODS: The feasibility of
      using the stable isotope of carbon, 13C, as a potential chemical marker for
      Anopheles arabiensis was evaluated in the laboratory. Labeled-13C glucose was
      incorporated into the larval diet in a powder or liquid form. The contribution of
      adult sugar feeding to the total mosquito carbon pool and the metabolically
      active carbon pool was determined by tracing the decline of the enrichment of the
      adult male mosquito as it switched from a labeled larval diet to an unlabeled
      adult diet. This decline in the adult was monitored by destructive sampling of
      the whole mosquito and analyzed using isotope ratio mass spectrometry. RESULTS: A
      two-pool model was used to describe the decline of the 13C-enrichment of adult
      mosquitoes. The proportion of the total adult carbon pool derived from the adult
      sugar diet over the life span of mosquitoes was determined and the ratio of
      structural carbon, with a low turnover rate to metabolically active non
      structural carbon was assessed. The uptake and turnover of sugar in the
      metabolically active fraction suggests that after 3 days >70% of the active
      fraction carbon is derived from sugar feeding (increasing to >90% by day 7),
      indicating the high resource demand of male mosquitoes. CONCLUSION: It was
      possible to "fix" the isotopic label in adult An. arabiensis and to detect the
      label at an appropriate concentration up to 21 days post-emergence. The optimum
      labeling treatment would cost around 250 US$ per million mosquitoes. Stable
      isotope marking may thus aid research on the fate of released insects besides
      other population-based ecological studies.

PMID- 16445866
TI  - Tissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose
      administered through intramuscular delivery.
AB  - In order to assess a new strategy of DNA vaccine for a more complete
      understanding of its action in immune response, it is important to determine the
      in vivo biodistribution fate and antigen expression. In previous studies, our
      group focused on the prophylactic and therapeutic use of a plasmid DNA encoding
      the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an
      efficient immune response induction as well as protection against virulent M.
      tuberculosis challenge. In the present study, we examined in vivo tissue
      distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration
      and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several
      tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body.
      The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65
      message for at least 15 days in muscle or liver tissue from immunized mice. We
      also analyzed the methylation status and integration of the injected plasmid DNA
      into the host cellular genome. The bacterial methylation pattern persisted for at
      least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in
      mammalian tissue, and Southern blot analysis showed that plasmid DNA was not
      integrated. These results have important implications for the use of DNA-Hsp65
      vaccine in a clinical setting and open new perspectives for DNA vaccines and new
      considerations about the inoculation site and delivery system.

PMID- 16445867
TI  - Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX
      2) inhibitors.
AB  - BACKGROUND: Epidemiologic and laboratory investigations suggest that nonsteroidal
      anti-inflammatory drugs (NSAIDs) have chemopreventive effects against breast
      cancer due to their activity against cyclooxygenase-2 (COX-2), the rate-limiting
      enzyme of the prostaglandin cascade. METHODS: We conducted a case control study
      of breast cancer designed to compare effects of selective and non-selective COX-2
      inhibitors. A total of 323 incident breast cancer patients were ascertained from
      the James Cancer Hospital, Columbus, Ohio, during 2003-2004 and compared with 649
      cancer free controls matched to the cases at a 2:1 ratio on age, race, and county
      of residence. Data on the past and current use of prescription and over the
      counter medications and breast cancer risk factors were ascertained using a
      standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were
      quantified by calculating odds ratios (OR) and 95% confidence intervals. RESULTS:
      Results showed significant risk reductions for selective COX-2 inhibitors as a
      group (OR = 0.29, 95% CI = 0.14-0.59), regular aspirin (OR = 0.49, 95% CI = 0.26
      0.94), and ibuprofen or naproxen (0.36, 95% CI = 0.18-0.72). Acetaminophen, a
      compound with negligible COX-2 activity and low dose aspirin (81 mg) produced no
      significant change in the risk of breast cancer. CONCLUSION: Selective COX-2
      inhibitors (celecoxib and rofecoxib) were only recently approved for use in 1999,
      and rofecoxib (Vioxx) was withdrawn from the marketplace in 2004. Nevertheless,
      even in the short window of exposure to these compounds, the selective COX-2
      inhibitors produced a significant (71%) reduction in the risk of breast cancer,
      underscoring their strong potential for breast cancer chemoprevention.

PMID- 16445869
TI  - [Populational alteration of cells in the intestinal intraepithelial layer and
      morphological changes of the intestinal wall elicited by Toxocara vitulorum
      infection in buffalo calves (Bubalus bubalis)].
AB  - To understand the development of the inflammatory responses in the wall of the
      gut, during the process of expulsion of the parasites from the host, samples of
      tissues were removed from the small intestines from four groups of naturally
      infected buffalo calves with Toxocara vitulorum during the beginning of the
      infection, at the peak of egg output, during the period of expulsion and post
      expulsion of the worms, as well as from uninfected calves. Cells (mast cells,
      eosinophils, intraepithelial lymphocytes - IEL and goblet cells) present in the
      epithelial layer (intraepithelial) of the small intestine were counted. In the
      duodenum, jejunum and ileum, the population of mast cells, eosinophils and
      lymphocytes increased significantly during the peak of the infection. Goblet cell
      numbers increased also during the beginning and at the peak of the infection. The
      decline of the number of these cells occurred during the periods of expulsion of
      the worms reaching to uninfected control counts at the post-expulsion period
      indicating a role of these cells in the process of expulsion of T. vitulorum by
      the buffalo calves. The layers of the intestinal wall (villus, crypt, submucosa
      and muscular) were also measured. Morphological examinations showed a significant
      vilar atrophy, particularly in the duodenum during the beginning, peak and during
      the period of expulsion of the worms, but smooth muscle hypertrophy or other
      alteration was not observed in any period of the infection.

PMID- 16445868
TI  - Protein kinases associated with the yeast phosphoproteome.
AB  - BACKGROUND: Protein phosphorylation is an extremely important mechanism of
      cellular regulation. A large-scale study of phosphoproteins in a whole-cell
      lysate of Saccharomyces cerevisiae has previously identified 383 phosphorylation
      sites in 216 peptide sequences. However, the protein kinases responsible for the
      phosphorylation of the identified proteins have not previously been assigned.
      RESULTS: We used Predikin in combination with other bioinformatic tools, to
      predict which of 116 unique protein kinases in yeast phosphorylates each
      experimentally determined site in the phosphoproteome. The prediction was based
      on the match between the phosphorylated 7-residue sequence and the predicted
      substrate specificity of each kinase, with the highest weight applied to the
      residues or positions that contribute most to the substrate specificity. We
      estimated the reliability of the predictions by performing a parallel prediction
      on phosphopeptides for which the kinase has been experimentally determined.
      CONCLUSION: The results reveal that the functions of the protein kinases and
      their predicted phosphoprotein substrates are often correlated, for example in
      endocytosis, cytokinesis, transcription, replication, carbohydrate metabolism and
      stress response. The predictions link phosphoproteins of unknown function with
      protein kinases with known functions and vice versa, suggesting functions for the
      uncharacterized proteins. The study indicates that the phosphoproteins and the
      associated protein kinases represented in our dataset have housekeeping cellular
      roles; certain kinases are not represented because they may only be activated
      during specific cellular responses. Our results demonstrate the utility of our
      previously reported protein kinase substrate prediction approach (Predikin) as a
      tool for establishing links between kinases and phosphoproteins that can
      subsequently be tested experimentally.

PMID- 16445870
TI  - [Seasonal distribution of gill parasites in fishes from fee-fishing at Guariba,
      Sao Paulo State, Brazil].
AB  - This study was accomplished with the objective of knowing the seasonal
      distribution of the main species of parasites causes of branchial damages to the
      fish from fee-fishing at Guariba, State of Sao Paulo. This city is situated at 21
      degrees 15'22'' S, 48 degrees 18'58'' W, in altitude 595 meters. This research
      was conducted between April, 1997 to March, 1999. From 408 fishes examined, 29.1%
      of them were infested by the protozoans e metazoans. Leporinus macrocephalus
      showed the highest parasitism by Trichodina sp., although Piaractus mesopotamicus
      and Cyprinus carpio were also parasited. Piscinoodinium pillulare infestation
      were found in L. macrocephalus, P. mesopotamicus, C. carpio e Colossoma
      macropomum. Monogenetics metazoan have largely been observed in L. macrocephalus,
      P. mesopotamicus, C. carpio, C. macropomum e cross-bred tambacu. The incidence of
      this parasite was elevated in the summer for L. macrocephalus, spring for P.
      mesopotamicus and C. macropomum, and both seasons for cross-bred tambacu. Lernaea
      cyprinacea copepodes were observed in L. macrocephalus, P. mesopotamicus, C.
      carpio and cross- breeding tambacu, in spite of the fact that C. carpio has
      demonstrated high parasitism of adult form. The fish L. macrocephalus, P.
      mesopotamicus and C. carpio were sponged intensely by Dolops carvalhoi, in
      situation of high population density. Piaractus mesopotamicus was considered the
      species more parasited by myxosporideos, that were also observed in L.
      macrocephalus and cross-breeding tambacu.

PMID- 16445871
TI  - [Parasitism of Hoplias malabaricus (Bloch, 1794) (Characiformes, Erythrinidae) by
      Quadrigyrus machadoi Fabio, 1983 (Eoacanthocephala, Quadrigyridae) at a pond,
      Aguai, State of Sao Paulo, Brazil].
AB  - The parasitism of trahira, Hoplias malabaricus, by the acanthocephalan
      Quadrigyrus machadoi was studied. Fish were collected at a pond located on
      Palmeiras Farm (21 degrees 59'19''S, 47 degrees 12'04''W), municipal district of
      Aguai, Sao Paulo, Brazil, during the period of January, 2002 to May, 2003. Among
      the 64 specimens analyzed, 56 (prevalence=87.5%) were infected with three to 573
      specimens of Quadrigyrus machadoi (mean intensity=119.0+/- 120.6 and mean
      abundance=104.1+/-119.4). Most of the parasites were found in the mesenterium as
      cystacanths. Some fish contained adult female parasites in the intestine, but
      gravid females were not verified. Parasite indices were analyzed in relation to
      the biological parameters of sex and standard length of the trahira, as well as
      with regard to the dry and the rainy periods defined for the area. No differences
      in parasite indices between sexes were found. The smaller specimens were the most
      extensively infected and had higher intensities of infection than fish of greater
      lengths. No seasonal variations in prevalence, mean intensity of infection and
      mean abundance values were found. The health of the fish was not influenced by
      the presence of parasites, as shown by the relative condition factor.

PMID- 16445872
TI  - [Community ecology of metazoan parasites of Cyphocharax gilbert (Quoy e Gaimard,
      1824) (Characiformes: Curimatidae) from Guandu river, State of Rio de Janeiro,
      Brazil].
AB  - Sixty specimens of Sairu Cyphocharax gilbert (Quoy and Gaimard, 1824) from River
      Guandu, (22 degrees 48'32'S, 43 degrees 37'35''"W), State of Rio de Janeiro,
      Brazil were studied for their metazoan parasites during May 2004 and February
      2005. A total of seven species of metazoan parasites were collected and
      identified: Sphinctero- diplostomum musculosum (metacercariae), Diplostomum (A.)
      compactum (metacercariae), Zonocotyloides haroltravassosi, Cosmoxynemoides
      aguirrei, Travnema araujoi, Raphidascaris sp. (larval) and Placobdella sp.
      Sphincterodiplostomum musculosum (Diplostomidae) founded in the eyes, was the
      more prevalent (40%) with highest mean intensity value (11.2). The nematodes C.
      aguirrei and T. araujoi (Pharyngodonidae) showed prevalence higher than 10%. Only
      S. musculosum showed significant correlation between the host total length and
      the parasite abundance. The parasite species richness showed a mean value of 0.9
      + 0.88 (0-3). The evaluation of the effect of host sex on parasite prevalence and
      abundance not showed significant results. The metazoan parasite community of C.
      gilbert is characterized by the low species diversity and for dominance of
      species with low values of prevalence.

PMID- 16445873
TI  - Metazoan parasites of Conorhynchos conirostris (Valenciennes, 1840) an endemic
      siluriform fish of the Sao Francisco basin, Brazil.
AB  - Specimens of Conorhynchos conirostris (Valenciennes, 1840) (Osteichthyes:
      Siluriformes) were collected from the upper Sao Francisco River (18 degrees
      12'32''S, 45 degrees 15'41''W) in the municipality of Tres Marias, Minas Gerais,
      Brazil, to investigate their parasitofauna. Of the 24 pira fish collected, 8 were
      male (33.3%) and 16 were female (66.7%). Of this total, 12 were parasitized
      (50%). Nine species of parasites were found: Helobdella sp., Creptotrema
      creptotrema Travassos, Artigas & Pereira, 1928; Palaeocryptogonimus claviformis
      Szidat, 1954; metacercariae of Clinostomum sp. and of Austrodiplostomum compactum
      (Lutz 1928); Procamallanus (Spirocamallanus) sp. (young specimen); larvae of
      Anisakidae and Rhabdochona sp.; and Neoechinorhynchus sp. (young specimen).
      Helobdella sp. had the highest prevalence, followed by C. creptotrema (most
      abundant) and P. claviformis. Creptotrema creptotrema was dominant species in the
      parasite community of C. conirostris. There was no influence of the host size and
      sex on the prevalence and abundance of parasites, with P. claviformis being found
      only in male hosts. With the exception of Procamallanus (Spirocamallanus) sp.,
      this was the first record of these parasites in C. conirostris.

PMID- 16445874
TI  - [Space-temporal distribution of Boophilus microplus (Acari: Ixodidae) ticks
      analyzed by geoprocessing in the municipality of Seropedica, state of Rio de
      Janeiro, Brazil].
AB  - The Geo-Environmental System of the Federal University of Rio de Janeiro was used
      with the objective of analyzing the space-temporal distribution of Boophilus
      microplus ticks in the municipality of Seropedica in different types of pasture,
      breeding and animal density. Geo-environmental variables, climatic parameters,
      type of pasture, breeding and animal densities were evaluated and the results
      were signed. The pasture areas were categorized as very favorable, favorable,
      little favorable and unfavorable to the development of B. microplus. The lowest
      favorable rates occurred in the summer and the highest favorable rates occurred
      in the winter. In the summer, 100% of the areas were unfavorable with animal
      densities from 1.1 to 1.4 animal unit per hectare (AUH), native pastures and
      resistant animals. On the other hand, with susceptible animals, keeping the same
      conditions, the areas were classified as little favorable. Favorability was
      similar for animal densities from 0.5 to 1.4 AUH and was higher for animal
      densities from 1.5 to 1.9 AUH. In the winter, the areas were unfavorable with
      similar rates when resistant animals, with densities < 0.5AUH, native and mixed
      pastures were used. However, the area of occurrence of ticks was enlarged when
      cultivated pastures were used. Keeping the same conditions, but using susceptible
      animals, the favorability rate changed to little favorable for native and mixed
      pastures, expanding to favorable in cultivated pastures. The methodology used
      allowed the identification and the quantification of areas of occurrence of B.
      microplus, as well as its temporal distribution and the effects of animal
      density, breeding and pasture variations.

PMID- 16445875
TI  - Haemogregarine parasites (Apicomplexa: Hepatozoidae) in Caiman crocodilus yacare
      (Crocodilia: Alligatoridae) from Pantanal, Corumba, MS, Brazil.
AB  - Haemogregarines were recorded in caimans Caiman crocodilus yacare from Pantanal.
      This study was carried out in seasonal ponds at the Miranda- Abobral subregion of
      Pantanal, State of Mato Grosso do Sul, western Brazil, from 1998 to 1999. Smears
      from 28 caimans were examined and 20 (71.4%) presented infection by a
      haemogregarine. Infections were observed in 11 males and 9 females. Morphological
      and morphometric observations suggest that the parasite forms found in this work
      are Hepatozoon caimani.

PMID- 16445882
TI  - Importance of physical vs. chemical interactions in surface shear rheology.
AB  - The stability of adsorbed protein layers against deformation has in literature
      been attributed to the formation of a continuous gel-like network. This
      hypothesis is mostly based on measurements of the increase of the surface shear
      elasticity with time. For several proteins this increase has been attributed to
      the formation of intermolecular disulfide bridges between adsorbed proteins.
      However, according to an alternative model the shear elasticity results from the
      low mobility of the densely packed proteins. To contribute to this discussion,
      the actual role of disulfide bridges in interfacial layers is studied. Ovalbumin
      was thiolated with S-acetylmercaptosuccinic anhydride (S-AMSA), followed by
      removal of the acetylblock on the sulphur atom, resulting in respectively blocked
      (SX) and deblocked (SH) ovalbumin variants. This allows comparison of proteins
      with identical amino acid sequence and similar globular packing and charge
      distribution, but different chemical reactivity. The presence and reactivity of
      the introduced, deblocked sulfhydryl groups were confirmed using the sulfhydryl
      disulfide exchange index (SEI). Despite the reactivity of the introduced
      sulfhydryl groups measured in solution, no increase in the surface shear
      elasticity could be detected with increasing reactivity. This indicates that
      physical rather than chemical interactions determine the surface shear behaviour.
      Further experiments were performed in bulk solution to study the conditions
      needed to induce covalent aggregate formation. From these studies it was found
      that mere concentration of proteins (to 200 mg/mL, equivalent to a surface
      concentration of around 2 mg/m(2)) is not sufficient to induce significant
      aggregation to form a continuous network. In view of these results, it was
      concluded that the adsorbed layer should not be considered a gelled network of
      aggregated material (in analogy with three-dimensional gels formed from heating
      protein solutions). Rather, it would appear that the adsorbed proteins form a
      highly packed system of proteins with net-repulsive interactions.

PMID- 16445881
TI  - Decrease of type IV collagen and TIMP-1 serum levels after splenectomy in
      patients with schistosomiasis mansoni.
AB  - The role of the spleen in the process of liver fibrosis in schistosomiasis still
      needs clarification. The aim of this study was to assess the effect of
      splenectomy on serum levels of two markers of fibrosis, type IV collagen and TIMP
      1, in patients with schistosomiasis mansoni. Twenty-four patients with
      hepatosplenic schistosomiasis mansoni participated in the study. Type IV collagen
      and TIMP-1 serum levels were measured preoperatively, and after 2 (POD-1) and 60
      days (POD-2) of spleen removal. Before splenectomy, both type IV collagen and
      TIMP-1 serum levels were elevated in the majority of patients. After splenectomy,
      the levels of type IV collagen showed a significant decrease in relation to the
      preoperative values both in POD-1 (median pre-splenectomy: 143.7 ng/ml versus
      77.01 ng/ml; p=0.04) and POD-2 (103.3 ng/ml; p=0.015). Serum levels of TIMP-1
      also showed a significant decrease in relation to the preoperative values both in
      POD-1 (pre-splenectomy: 585.9 ng/ml versus 196.4 ng/ml; p=0.008) and POD-2 (97.4
      ng/ml; p<0.001). There was no difference between POD-1 and POD-2 values for each
      serum marker. In conclusion, splenectomy in schistosomotic patients was
      associated with a decrease in serum markers of fibrosis levels, which persisted
      for at least 60 days. These results suggest that the spleen may play a role in
      the extra cellular matrix production, and therefore may contribute to liver
      fibrosis in schistosomiasis mansoni.

PMID- 16445883
TI  - Reduced transglutaminase-catalyzed protein aggregation is observed in the
      presence of creatine using sedimentation velocity.
AB  - Transglutaminases (TGases) are enzymes that catalyze covalent isopeptide
      crosslinks between reactive lysine and glutamine residues in proteins. Higher
      than normal local concentrations of TGase have been correlated with increased
      protein aggregation in vivo. These insoluble protein aggregates are the hallmark
      of several neurodegenerative diseases, including Alzheimer's, Parkinson's, and
      Huntington's diseases, although each aggregating protein involved is disease
      specific. Because TGase is implicated in protein aggregation, there is evidence
      that its regulation may retard disease progression. Here we report on a laser
      light transmission technique as an in vitro tool to gauge the efficacy of
      creatine, a candidate inhibitor, to regulate aggregation. Sedimentation
      velocities of protein-coated particles in TGase-containing water-glycerol
      solutions were tracked with different levels of creatine. Sedimentation
      velocities were converted to apparent aggregate sizes using Stoke's law of
      sedimentation. The results indicated that creatine promoted up to a 20% reduction
      in protein aggregation in vitro. This technique may prove to be useful in
      identifying other functional TGase inhibitors.

PMID- 16445884
TI  - A reassessment of semiquantitative analytical procedures for DNA methylation:
      comparison of bisulfite- and HpaII polymerase-chain-reaction-based methods.
AB  - Two techniques in particular are used to study site-specific DNA methylation:
      genomic sequencing after bisulfite modification and polymerase chain reaction
      after digestion by a methylation-sensitive endonuclease (usually HpaII). Only the
      former methodology assesses the methylation status of all the cytosine residues
      in the DNA sequence, but it is so complex and time consuming that the latter
      procedure, though limited to the restriction sites recognized by the
      endonuclease(s) used, is often preferred at least for a first analysis. In this
      work we investigate differences between these two techniques in the assessment of
      DNA methylation and offer some suggestions on how to avoid uncorrected results.
      Although there is substantial accordance in the results obtained using these
      different techniques, we observed a general overestimate for methylation levels
      above 30% and a general underestimate for methylation levels below this value
      using the HpaII/PCR technique in the study of methylation of the 5'-flanking
      region of the mouse myogenin gene in cultured muscle cells and mouse tissues.

PMID- 16445885
TI  - Cloning and characterization of a lupeol synthase involved in the synthesis of
      epicuticular wax crystals on stem and hypocotyl surfaces of Ricinus communis.
AB  - Pentacyclic triterpenoids are a large group of secondary metabolites found in
      many different plant species, either as glycoside conjugates or as aglycones. The
      latter in many cases accumulate to high amounts in the cuticular wax and hence at
      the surface of plant organs. In the present work, the cuticle-specific formation
      of triterpenoids was investigated in Ricinus communis stems, combining analytical
      and molecular genetic methods. Two phenotypes of castor bean could be
      distinguished based on the glaucous or glossy appearance of the surfaces of all
      stem portions including the hypocotyls, and were due to the presence or absence
      of thread-shaped epicuticular wax crystals, respectively. Comparative studies
      showed that these crystals are formed by the triperpenoid lupeol, present in high
      amounts on all stem surfaces. On the hypocotyl portion of stems, lupeol was found
      to accumulate rapidly during early development of the surface (10-15 days after
      emergence). Mature hypocotyls of glossy individuals were covered with 12.5
      microg/cm2 of wax containing approximately 1% of lupeol, whereas the glaucous
      phenotype had a wax load of 51.9 microg/cm2 with 56% of lupeol. Two oxidosqualene
      cyclases from castor bean were cloned, functionally expressed in yeast, and
      characterized as a cycloartenol synthase (RcCAS) and a lupeol synthase (RcLUS).
      Phylogenetic analyses revealed that RcLUS is similar to two clades of known
      lupeol synthases, but also exhibits some similarities with beta-amyrin synthases.
      Both the organ-specific expression of RcLUS and the expression pattern during
      hypocotyl development exactly matched the accumulation of cuticular lupeol in
      castor bean. In contrast, RcCAS was constitutively expressed in all organs at
      various times. We conclude that the RcLUS enzyme is responsible for formation of
      the cuticular lupeol, and thus for the characteristic surface properties of R.
      communis stems.

PMID- 16445886
TI  - Lanosterol biosynthesis in plants.
AB  - Plants biosynthesize sterols from cycloartenol using a pathway distinct from the
      animal and fungal route through lanosterol. Described herein are genome-mining
      experiments revealing that Arabidopsis encodes, in addition to cycloartenol
      synthase, an accurate lanosterol synthase (LSS)--the first example of lanosterol
      synthases cloned from a plant. The coexistence of cycloartenol synthase and
      lanosterol synthase implies specific roles for both cyclopropyl and conventional
      sterols in plants. Phylogenetic reconstructions reveal that lanosterol synthases
      are broadly distributed in eudicots but evolved independently from those in
      animals and fungi. Novel catalytic motifs establish that plant lanosterol
      synthases comprise a third catalytically distinct class of lanosterol synthase.

PMID- 16445887
TI  - Fragile self-esteem and affective instability in posttraumatic stress disorder.
AB  - Temporal fluctuations in self-esteem and affect are prominent features of several
      clinical conditions (e.g., depression), but there is an absence of empirical work
      examining their role in posttraumatic stress disorder (PTSD). Individuals who
      experience large fluctuations in self-evaluations and affect are considered more
      vulnerable to psychopathology than individuals able to adequately modulate their
      self-image and emotional responses. We examined the relevance of self-esteem and
      affective instability to PTSD. Veterans with and without PTSD completed 14 daily
      ratings of self-esteem, positive affect, negative affect, and gratitude. Compared
      to veterans without PTSD, veterans with PTSD exhibited more temporal fluctuations
      in self-esteem, negative affect, and gratitude, with a smaller effect for
      positive affect. For all veterans, self-esteem and negative affective instability
      was associated with diminished well-being. Except for self-esteem instability,
      most findings were substantially reduced after accounting for variance
      attributable to PTSD diagnoses and mean intensity levels over the 14-day
      monitoring period. These data suggest self-esteem instability is important in
      understanding the lives of veterans with and without PTSD.

PMID- 16445888
TI  - On the feeling of doing: dysphoria and the implicit modulation of authorship
      ascription.
AB  - The experience of authorship arises when we feel that observed effects (e.g., the
      onset of a light) are caused by our own actions (e.g., pushing a switch). This
      study tested whether dysphoric persons' authorship ascription can be modulated
      implicitly in a situation in which the exclusivity of the cause of effects is
      ambiguous. In line with the idea that depressed individuals' self-schemata
      include general views of uncontrollability, in a subliminal priming task we
      observed that dysphoric (compared with nondysphoric) participants experienced
      lower authorship of action effects when the self-concept was primed. Priming the
      potential effects of an action just prior to their occurrence, however, increased
      experiences of authorship in all participants and eliminated the effect of self
      concept priming on dysphoric participants' authorship experiences. These findings
      suggest that the human mental system seizes on a match between primed and actual
      action effect to establish a sense of authorship, even in a state of depression
      when persons have weak self-views of causing behavioral outcomes.

PMID- 16445889
TI  - Cortical expressions of inhibition of return.
AB  - Inhibition of return (IOR) is a phenomenon that has been thought to be closely
      associated with attention mechanisms. In particular, it might arise from the
      operation of an attentional mechanism that facilitates visual search by
      inhibiting both covert attention and eye movements from returning to recently
      inspected locations. Although IOR has received a great deal of research interest,
      and mechanisms involving sensory, perceptual, and motor consequences have been
      proposed, no consensus has yet been reached regarding the stages of information
      processing at which IOR operates. In the present study, we utilized event-related
      potential (ERP) measures of visual and motor processes to investigate the
      processing changes underlying IOR. In three experiments, involving localization,
      detection, or Go-NoGo discrimination, participants were required to make manual
      responses to target stimuli. In each of these experiments, IOR was associated
      with a slowing of premotor processes as indicated by a modulation of the onset of
      the target-locked lateralized readiness potential (LRP). However, the duration of
      motor processes was not affected (response-locked LRP latency). Consistent with a
      perceptual locus of IOR, the amplitudes of the occipital ERP peaks were reduced
      for targets at cued locations relative to those at uncued locations. These and
      earlier results together provide considerable support for a model in which
      salience mechanisms that guide attention orienting are also affected by IOR, in
      that processing a stimulus at a location results in a lowering of its salience
      for future processing, making orienting to that location, and responding to
      targets presented there, more time consuming.

PMID- 16445890
TI  - Role of V1a vasopressin receptors in the control of aggression in Syrian
      hamsters.
AB  - The present study investigated the hypothesis that social isolation increases
      aggression by increasing the number of V1a vasopressin receptors in the anterior
      hypothalamus (AH). Male hamsters were randomly assigned to a group that was
      allowed to interact with a small nonaggressive hamster three times each week for
      3 weeks (socially experienced) or to a group that did not interact socially with
      other hamsters (social isolates). On the final day of the experiment, hamsters in
      both groups were placed in a neutral arena with a small, nonaggressive intruder,
      and agonistic behavior was scored for 10 min. In social isolates, the duration of
      aggression and the number of attacks were significantly greater than in socially
      experienced hamsters. There were no significant between-group differences in the
      latency to the onset of aggression, the number of flank marks or in the duration
      of defensive/submissive, social or nonsocial behavior. The amount of V1a receptor
      binding was significantly greater in the AH, the paraventricular nucleus of the
      hypothalamus and the lateral hypothalamus in the social isolates than in the
      socially experienced hamsters. The amount of V1a receptor binding was
      significantly greater in the central amygdala of socially experienced hamsters
      than in socially isolated hamsters. Serum concentrations of testosterone were
      significantly higher in the socially experienced hamsters than in social
      isolates. These data support the hypothesis that social isolation increases
      aggression by increasing the number of V1a vasopressin receptors in the AH.

PMID- 16445891
TI  - Artificial N-functionalized UDP-glucosamine analogues as modified substrates for
      N-acetylglucosaminyl transferases.
AB  - Analogues of UDP-GlcNAc modified at the 2-acetamido group of the GlcNAc moiety
      were prepared in order to study their role in the mechanism of N
      acetylglucosaminyl transferase mediated glycosylation reactions. The structural
      analogues with N-formyl-, N-propionyl-, N-butyryl- and N-isobutyryl-groups were
      synthesized, utilizing the morpholidate coupling method starting from d
      glucosaminyl-1-phosphate after selective N-acylation of its amino group with the
      appropriate N-acyloxysuccinimide esters as well as a chlorinated formylformiate.

PMID- 16445892
TI  - Screening for hetero-transglycosylating activities in extracts from nasturtium
      (Tropaeolum majus).
AB  - Using combinations of different polysaccharides as glycosyl donors and of
      oligosaccharides fluorescently labeled by sulforhodamine (SR) as glycosyl
      acceptors, we screened for the presence of transglycosylating activities in
      extracts from nasturtium (Tropaeolum majus). Besides xyloglucan
      endotransglycosylase/hydrolase (XTH/XET, EC 2.4.1.207) activity, which transfers
      xyloglucanosyl residues from xyloglucan (XG) to XG-derived oligosaccharides
      (XGOs), a glycosyl transfer from XG to SR-labeled cellooligosaccharides and
      laminarioligosaccharides has been detected. The XGOs also served as acceptors for
      the glycosyl transfer from soluble cellulose derivatives carboxymethyl cellulose
      and hydroxyethylcellulose. The effectivity of these polysaccharides as glycosyl
      donors for transfer to XG-derived octasaccharide [1-3H]XXLGol decreased in the
      order XG > HEC > CMC. Isoelectric focusing in polyacrylamide gels showed that
      bands corresponding to hetero-transglycosylase activities coincided with zones
      corresponding to XTH/XET. These results can be explained as due either to
      substrate non-specificity of certain isoenzymes of XTH/XET or to existence of
      enzymes catalyzing a hetero-transfer, that is the formation of covalent linkages
      between different types of carbohydrate polymers.

PMID- 16445893
TI  - Degradation of high-molecular-weight hyaluronan by hydrogen peroxide in the
      presence of cupric ions.
AB  - Dynamic viscosity (eta) of the high-molecular-weight hyaluronan (HA) solution was
      measured by a Brookfield rotational viscometer equipped with a Teflon cup and
      spindle of coaxial cylindrical geometry. The decrease of eta of the HA solution,
      indicating degradation of the biopolymer, was induced by a system containing H2O2
      alone or H2O2 plus CuCl2. The reaction system H2O2 plus CuCl2 as investigated by
      EPR spin-trapping technique revealed the formation of a four-line EPR signal
      characteristic of a *DMPO-OH spin adduct. Thus, hydroxyl radicals are implicated
      in degradation of high-molecular-weight HA by the system containing H2O2 and
      CuCl2.

PMID- 16445894
TI  - Structural elucidation of the core-lipid A backbone from the lipopolysaccharide
      of Acinetobacter radioresistens S13, an organic solvent tolerant Gram-negative
      bacterium.
AB  - The structure of the core oligosaccharide of the lipopolysaccharide from an
      organic solvent tolerant Gram-negative bacterium, Acinetobacter radioresistens
      S13, was investigated by chemical analysis, NMR spectroscopy and MALDI-TOF mass
      spectrometry. All the experiments were performed on the oligosaccharides obtained
      either by alkaline degradation or mild acid hydrolysis. The data showed the
      presence of two novel oligosaccharide molecules containing a trisaccharide of 3
      deoxy-D-manno-octulopyranosonic acid in the inner core region and a glucose rich
      outer core whose structure is the following: [structure: see text] R=H in the
      main oligosaccharide and beta-Glc in the minor product. The bacterium was grown
      on aromatic (phenol and benzoic acid) and nonaromatic carbon sources and the core
      oligosaccharide resulted to occur always with this novel structure.

PMID- 16445895
TI  - Additive effects in the modeling of oligosaccharides with MM3 at high dielectric
      constants: an approach to the 'multiple minimum problem'.
AB  - The production of an adiabatic map for a di- or trisaccharide requires the
      generation of many relaxed maps, ideally 59,049 for a disaccharide or 4,782,969
      for a trisaccharide composed by hexose residues, due to a combination of
      exocyclic angle torsions. As the production of this amount of maps is usually
      ruled out for time considerations, different approaches were exploited. When
      working at low dielectric constants, starting points originated in cooperative
      hydrogen bonds through the rings are usually sufficient to produce an adiabatic
      map, but at higher dielectric constants those circuits are meaningless, and many
      low-energy conformers appear in each energy well. Herein, different conformations
      of four disaccharides (beta-4-linked mannobiose, and three galactobioses, linked
      alpha-(1-->3), alpha-(1-->4), and beta-(1-->4)) and one trisaccharide (beta-4
      linked mannotriose) were minimized using mm3 at epsilon = 80, and the difference
      in energy produced by changes in torsional angles was recorded. A remarkable
      additive effect was found to occur when the exocyclics were gathered in groupings
      of two or three neighboring angles. Thus, in most cases, each grouping can be
      studied separately, and the minimum energy conformers can be predicted without
      the need of resorting to thousands of calculations. In some cases where two
      protons of different groups show steric interactions in some specific
      conformations, small deviations of the additivity were encountered. Anyway, a
      complex system with many variables can be transformed in one with many fewer
      variables, thus simplifying further studies. An attempt to calculate the same
      effect at epsilon = 3 shows that hydrogen bonding and electrostatic interactions
      make impossible to find those additive effects, thus precluding its utilization
      at such low dielectric constants.

PMID- 16445896
TI  - Blocking intrahepatic deletion of activated CD8+ T cells by an altered peptide
      ligand.
AB  - BACKGROUND: Activated CD8(+) T cells are retained by the healthy liver where the
      majority undergo apoptosis. The intrahepatic apoptosis of activated CD8(+) T
      cells is enhanced by the presence of SIINFEKL peptide. It is of great interest to
      identify strategies for maintaining intrahepatic T cell number and function in
      the presence of SIINFEKL peptides. AIM: Our aim was to test if low affinity
      peptides can block SIINFEKL peptide induced T cell deletion. METHODS: We used an
      in vivo model of intrahepatic CD8(+) T cell deletion with peptides of different
      affinities. RESULTS AND DISCUSSION: We show that the intrahepatic deletion of
      CD8(+) T cells by SIINFEKL peptide results in loss of in vivo cytotoxic T
      lymphocyte function. In contrast we show that a low affinity peptide (G4) does
      not result in intrahepatic deletion of CD8(+) T cells. High concentrations G4
      peptide can however block intrahepatic deletion of activated CD8(+) T cells, and
      prevent loss of in vivo cytotoxicity due to SIINFEKL peptide. This is the first
      demonstration of blocking of SIINFEKL peptide induced CD8(+) T cell deletion in
      the liver, with enhancement of in vivo cytotoxicity.

PMID- 16445897
TI  - Acute liver damage induced by 2-nitropropane in rats: effect of diphenyl
      diselenide on antioxidant defenses.
AB  - The effect of post-treatment with diphenyl diselenide on liver damage induced by
      2-nitropropane (2-NP) was examined in male rats. Rats were pre-treated with a
      single dose of 2-NP (100 mg/kg body weight dissolved in canola oil). Afterward,
      the animals were post-treated with a dose of diphenyl diselenide (10, 50 or 100
      micromol/kg). The parameters that indicate tissue damage such as liver
      histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), gamma-glutamyl transferase (GGT), urea and creatinine were determined.
      Since the liver damage induced by 2-NP is related to oxidative damage, lipid
      peroxidation, superoxide dismutase (SOD), catalase (CAT) and ascorbic acid level
      were also evaluated. Diphenyl diselenide (50 and 100 micromol/kg) effectively
      restored the increase of ALT and AST activities and urea level when compared to
      the 2-NP group. At the higher dose, diphenyl diselenide decreased GGT activity.
      Treatment with diphenyl diselenide, at all doses, effectively ameliorated the
      increase of hepatic and renal lipid peroxidation when compared to 2-NP group. 2
      NP reduced CAT activity and neither alter SOD activity nor ascorbic acid level.
      This study points out the involvement of CAT activity in 2-NP-induced acute liver
      damage and suggests that the post-treatment with diphenyl diselenide was
      effective in restoring the hepatic damage induced by 2-NP.

PMID- 16445898
TI  - Nitrite reduces the effects of HOCl on unsaturated phosphatidylcholines--a MALDI
      TOF MS study.
AB  - The concentration of nitrite (NO2-) increases under inflammatory conditions.
      However, the physiological role of nitrite is so far controversial discussed: it
      was reported that effects of HOCl (an important inflammation mediator) on
      phospholipids (PL) may be enhanced but also reduced in the presence of nitrite.
      In this paper a simple model system was used: unsaturated phosphatidylcholine
      (PC) vesicles were treated with HOCl in the presence of varying NaNO2
      concentrations and the yield of reaction products was determined by MALDI-TOF MS:
      the extent of chlorohydrin generation was significantly reduced in the presence
      of NaNO2 because HOCl is consumed by the oxidation of NO2- to NO3-. Similar
      results were obtained when HOCl was generated by the myeloperoxidase
      (MPO)/H2O2/Cl- system or the experiments were carried out in the presence of a
      simple peptide. It is concluded that the transient products of the reaction
      between HOCl and NO2- do not have a sufficient reactivity to modify PL.

PMID- 16445899
TI  - Ethnicity affects the distribution of delta-aminolevulinic acid dehydratase
      (ALAD) genetic variants.
AB  - BACKGROUND: delta-Aminolevulinic acid dehydratase (ALAD) catalyzes the second
      step of heme synthesis. The ALAD gene shows a polymorphism (G-to-C transversion
      at position 177) leading to 2 alleles (ALAD1 and ALAD2) and 3 phenotypes (ALAD 1
      1, ALAD 1-2 and ALAD 2-2). This polymorphism has been shown to affect lead
      toxicity and the risk of meningioma. In addition, there is little evidence
      showing interethnic differences in the distribution this polymorphism, especially
      in heterogeneous populations such as the present-day Brazilian population. We
      examined the distribution of genetic variants of the G177C ALAD polymorphism in
      black and white Brazilians. METHODS: We studied 115 subjects self-reported as
      black and 119 subjects as white (total N=234; 135 men and 99 women; age range: 18
      60 years). Genomic DNA was extracted from venous blood and the genotypes for the
      ALAD polymorphism were determined by PCR followed by RFLP digestion and gel
      electrophoresis. RESULTS: We found a notable interethnic disparity in the
      distribution of G177C ALAD genotypes and alleles. The ALAD2 allele was more
      common in whites (12%) than in blacks (4%) (P<0.05). Correspondingly, the
      heterozygote (ALAD 1-2) or homozygote variant (ALAD 2-2) genotypes for this
      polymorphism were more common in whites than in blacks (P<0.05). CONCLUSIONS: The
      significant interethnic differences in the distribution of G177C ALAD variants
      found in the Brazilian population is consistent with differences previously
      reported in other countries. These findings may help us understand the
      interethnic disparities in susceptibility to lead toxicity and brain tumors.

PMID- 16445900
TI  - The influence of HIV infection on the correlation between plasma concentrations
      of monocyte chemoattractant protein-1 and carotid atherosclerosis.
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in
      atherosclerosis and it has been recently proposed as a surrogate biomarker of
      long-term clinical outcomes in patients with acute myocardial infarction. Little
      is known of the factors that may influence plasma MCP-1 concentrations. METHODS:
      We studied 384 healthy volunteers and 226 HIV-infected patients as a model of
      chronic inflammatory condition that predisposes to sub-clinical atherosclerosis.
      RESULTS: In healthy participants there were significant associations between
      plasma MCP-1 concentration and age, smoking status, and serum triglyceride
      concentrations that were not observed in the HIV-infected patients. The plasma
      concentration of MCP-1 was significantly associated with the polymorphism at
      position -2518 of the MCP-1 gene and, in patients, with the carotid artery intima
      media thickness. There were also significant correlations indicating a close
      association between MCP-1 and HIV disease activity. However, in a multiple
      regression model, only age, the MCP-1 genotype and smoking status showed
      significant, and independent, associations with plasma MCP-1 concentrations.
      CONCLUSION: Plasma MCP-1 concentration is genetically determined and associated
      with age and smoking habit and it also correlates with subclinical
      atherosclerosis in HIV-infected patients.

PMID- 16445902
TI  - A sensitive ELISA for serum ornithine carbamoyltransferase utilizing the
      enhancement of immunoreactivity at alkaline pH.
AB  - BACKGROUND: We developed a new enzyme-linked immunosorbent assay (ELISA) for
      ornithine carbamoyltransferase (OCT) and evaluated its usefulness. METHODS:
      Recombinant human OCT expressed in E. coli was used as an antigen to obtain the
      monoclonal antibodies for this assay. RESULTS: The reactivity of the antibodies
      to native OCT as well as recombinant OCT was enhanced at alkaline pH (8.5-10),
      and the assay's sensitivity was markedly improved. The antibodies react
      identically with native and recombinant OCT at pH 9.4. The dilution test showed a
      good linearity between dilution ratios and the concentrations. Different
      concentrations of OCT added were recovered on average at 90.4%. There was a good
      correlation between OCT protein levels in the ELISA and OCT enzyme activities
      (r=0.987, p<0.0001). A significant difference in the serum level of OCT was
      observed between chronic hepatitis patients (110.7+/-80 ng/ml) and healthy
      subjects (34.4+/-20.7 ng/ml) (p<0.0001). The serum levels of OCT between sexes
      differed significantly in the healthy subjects (p<0.0001). CONCLUSIONS: Our newly
      established ELISA for OCT using monoclonal antibodies is sensitive enough for
      clinical application.

PMID- 16445901
TI  - Detoxification of formate by formate dehydrogenase-loaded erythrocytes and
      carbicarb in folate-deficient methanol-intoxicated rats.
AB  - BACKGROUND: Formic acid is a toxic metabolite responsible for the metabolic
      acidosis in methanol poisoning. Formate dehydrogenase (EC 1.2.1.2) converts
      formate into CO2 in the presence of NAD. We examined the in vitro and in vivo
      efficiency of formate dehydrogenase-loaded carrier erythrocytes along with
      carbicarb in eliminating the formate in methanol-intoxicated folate-deficient
      rats. METHOD: Formate dehydrogenase-loaded erythrocytes were prepared by
      hypotonic dialysis method. Carbicarb (carb) (equimolar solution of sodium
      carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Folate
      depletion was induced by methotrexate (MTX) treatment. Experimental design
      consisted of 8 groups: saline control, methanol control, MTX control, ELE
      control, MTX-methanol control, MTX-methanol-carb, MTX-methanol-carb-ELE, and MTX
      MeOH-ELE group. Male Wistar rats treated with MTX (0.3 mg/kg) for a week were
      injected (i.p.) with methanol (4 g/kg). Twelve hours later, the carbicarb
      solution was infused, and then a formate dehydrogenase-loaded erythrocytes
      suspension (40% hematocrit) was infused (i.v.) in bolus. Blood samples were
      collected every hour for 4 h from the cannulated left jugular vein. Blood
      methanol and formate were estimated respectively with HPLC and fluorimetric
      assay. Blood pH, blood pO2, pCO2 and bicarbonate were also measured. RESULTS:
      There was marked elimination of formate in selected groups. CONCLUSION: Formate
      dehydrogenase-loaded erythrocytes, along with carbicarb, facilitates removal of
      formate, in methanol poisoning.

PMID- 16445903
TI  - Nucleosome regulator Xhmgb3 is required for cell proliferation of the eye and
      brain as a downstream target of Xenopus rax/Rx1.
AB  - Rax/Rx is a paired-type homeodomain-containing transcription factor that is
      essential for cell proliferation in the developing eye and brain. The molecular
      mechanisms that regulate cell proliferation by rax, however, are largely unknown.
      Here, we identify the high mobility group B3 gene (hmgb3) as a downstream target
      of Xenopus rax (Xrax/XRx1). Overexpression of Xhmgb3 results in an increase in
      eye and brain sizes due to promoted cell proliferation, while morpholino-oligo
      mediated knock down of Xhmgb3 reduces eye and brain sizes. In addition, ChIP
      assays showed that Xhmgb3 is recruited around the promoter region of c-myc to
      enhance c-myc transcription. We also found that XOptx2 requires rax for its
      initial expression. Furthermore, we show that Xhmgb3 and XOptx2 are required for
      retinal development mainly at different developmental stages. Our findings reveal
      a novel aspect of progenitor cell proliferation during embryonic central nervous
      system (CNS) development.

PMID- 16445904
TI  - Atrophin contributes to the negative regulation of epidermal growth factor
      receptor signaling in Drosophila.
AB  - Dentato-rubral and pallido-luysian atrophy (DRPLA) is a dominant, progressive
      neurodegenerative disease caused by the expansion of polyglutamine repeats within
      the human Atrophin-1 protein. Drosophila Atrophin and its human orthologue are
      thought to function as transcriptional co-repressors. Here, we report that
      Drosophila Atrophin participates in the negative regulation of Epidermal Growth
      Factor Receptor (EGFR) signaling both in the wing and the eye imaginal discs. In
      the wing pouch, Atrophin loss of function clones induces cell autonomous
      expression of the EGFR target gene Delta, and the formation of extra vein tissue,
      while overexpression of Atrophin inhibits EGFR-dependent vein formation. In the
      eye, Atrophin cooperates with other negative regulators of the EGFR signaling to
      prevent the differentiation of surplus photoreceptor cells and to repress Delta
      expression. Overexpression of Atrophin in the eye reduces the EGFR-dependent
      recruitment of cone cells. In both the eye and wing, epistasis tests show that
      Atrophin acts downstream or in parallel to the MAP kinase rolled to modulate EGFR
      signaling outputs. We show that Atrophin genetically cooperates with the nuclear
      repressor Yan to inhibit the EGFR signaling activity. Finally, we have found that
      expression of pathogenic or normal forms of human Atrophin-1 in the wing promotes
      wing vein differentiation and acts as dominant negative proteins inhibiting
      endogenous fly Atrophin activity.

PMID- 16445905
TI  - Expression and regulation of antioxidant enzymes in the developing limb support a
      function of ROS in interdigital cell death.
AB  - Vertebrate limb development is a well-studied model of apoptosis; however, little
      is known about the intracellular molecules involved in activating the cell death
      machinery. We have shown that high levels of reactive oxygen species (ROS) are
      present in the interdigital 'necrotic' tissue of mouse autopod, and that
      antioxidants can reduce cell death. Here, we determined the expression pattern of
      several antioxidant enzymes in order to establish their role in defining the
      areas with high ROS levels. We found that the genes encoding the superoxide
      dismutases and catalase are expressed in autopod, but they are downregulated in
      the interdigital regions at the time ROS levels increased and cell death was
      first detected. The possible role of superoxide and/or peroxide in activating
      cell death is supported by the protective effect of a superoxide
      dismutase/catalase mimetic. Interestingly, we found that peroxidase activity and
      glutathione peroxidase-4 gene (Gpx4) expression were restricted to the non
      apoptotic tissue (e.g., digits) of the developing autopod. Induction of cell
      death with retinoic acid caused an increase in ROS and decrease in peroxidase
      activity. Even more inhibition of glutathione peroxidase activity leads to cell
      death in the digits, suggesting that a decrease in antioxidant activity, likely
      due to Gpx4, caused an increase in ROS levels, thus triggering apoptosis.

PMID- 16445906
TI  - Dioxins: an overview.
AB  - This review article summarizes what is known about human health following
      exposure to dioxins. It is meant primarily for health professionals but was also
      written with the general public in mind. The need for such an article became
      apparent to the authors following media inquiries at the time the then Ukraine
      presidential candidate Victor Yushchenko was deliberately poisoned with the most
      toxic dioxin, tetrachlorodibenzodioxin or TCDD.

PMID- 16445907
TI  - dextro- and levo-morphine attenuate opioid delta and kappa receptor agonist
      produced analgesia in mu-opioid receptor knockout mice.
AB  - We have demonstrated that the antianalgesia induced by dextro-morphine and levo
      morphine is not mediated by the stimulation of mu-opioid receptors in male CD-1
      mice. We now report that the dextro-morphine and levo-morphine attenuated
      antinociception produced by delta-opioid receptor agonist deltorphin II and kappa
      opioid receptor agonist U50,488H given spinally in the male mu-opioid receptor
      knockout mice. The tail-flick response was used for the antinociceptive test.
      Intrathecal injection of levo-morphine (3 nmol) markedly inhibited the tail-flick
      response in wild type, partially in heterozygous, but not in homozygous mu-opioid
      receptor knockout mice. Intrathecal pretreatment with dextro-morphine (33 fmol)
      or levo-morphine (0.3 nmol) for 45 min also attenuated levo-morphine-produced
      antinociception in wide type mice. Intrathecal pretreatment with dextro-morphine
      (33 fmol) or levo-morphine (0.3 nmol) for 45 min attenuated the tail-flick
      inhibition produced by deltorphin II (12.8 nmol) and U50,488H (123.3 nmol) in
      wide type, heterozygous and homozygous mu-opioid receptor knockout mice. The
      findings provide additional evidence that mu-opioid receptors are not involved in
      the antianalgesia induced by dextro-morphine and levo-morphine.

PMID- 16445908
TI  - Cytokeratin profile in mucoepidermoid carcinoma is not related to its
      histological grading of malignancy.
AB  - The objective of this experiment was to determine the relationship between the
      expression of cytokeratins (CKs) and histologic grading in MEC. Eleven cases of
      MEC were selected and graded as low, intermediate and high-grade tumors. The
      expression of CKs 7, 8, 10, 13 and 14 was assessed immunohistochemically using
      streptavidin-biotin complex method. The results showed that the studied CKs were
      expressed in most cases of MEC, independently of histologic grading. Nonetheless,
      low-grade tumors demonstrated intense staining of CK 7 and 8; additionally, CK 10
      and 13 were more pronounced in this grade. The immunoexpression was variable
      according to cellular type and organization pattern of the tumor. Mucous cells
      were positive for CK 7 and 8; epidermoid cells were stained for CK 10, 13 and 14;
      CK 7, 8, 10 and 14 were observed in intermediate cells, and CK 7 was occasionally
      seen in clear cells. Cystic structures and duct-like elements in MEC were
      positive for CK 7 and 8, whereas solid nests showed positivity for all CKs. These
      results suggest that expression profile of these proteins does not reflect the
      biological behavior of MCE, however, it guides the detection of cellular types
      and differential diagnosis from other salivary gland tumors.

PMID- 16445909
TI  - HIV-1 Nef protects human-monocyte-derived macrophages from HIV-1-induced
      apoptosis.
AB  - HIV-1 Nef is the regulatory protein expressed earliest and most abundantly in the
      infection cycle. Its expression has been correlated with a plethora of effects
      detectable either in producer, target, and bystander cells, as well as in the
      viral particles. Even if the relationship between Nef expression and apoptosis
      has been already matter of investigation in infected lymphocytes, whose
      resistance to HIV infection is however limited to few days, this remains to be
      investigated in cells that in vivo well resist the HIV cytopathic effect. In such
      an instance, we were interested in establishing whether Nef influences the
      apoptotic processes in primary human-monocyte-derived macrophages (MDM). High
      efficiency HIV-1 infection of MDM allowed us to establish that virus-expressed
      Nef strongly counteracts the HIV-1-induced apoptosis. The Nef mutant analysis
      suggested that this effect relies on the interaction with different protein
      partners and cell compartments. We also observed that the Nef protection to the
      HIV-1-induced apoptosis correlated with the hyper-phosphorylation and consequent
      inactivation of the pro-apoptotic Bad protein. On the basis of these results, we
      propose the Nef anti-apoptotic effect as a relevant part of the mechanism of the
      in vivo establishment of the HIV macrophage reservoirs.

PMID- 16445910
TI  - A cell-free biochemical complementation assay reveals complex and redundant
      cytosolic requirements for LRP endocytosis.
AB  - The low density lipoprotein receptor-related protein (LRP) binds multiple,
      distinct ligands and participates in constitutive endocytosis and signal
      transduction. Using an in vitro reconstitution system and a new biochemical
      complementation assay, we have explored the limiting cytosolic requirements for
      endocytosis of LRP from isolated plasma membranes. We find that clathrin, AP2 and
      dynamin do not support efficient LRP uptake and that additional factors present
      in a 30% ammonium sulfate supernatant fraction of bovine brain cytosol (AS supt)
      are required. Fractionation of the AS supt revealed that multiple and redundant
      factors are required to support LRP endocytosis. Among these, we identified
      Hsc70, synaptojanin1 and CRMP-2 by mass spectrometry. Our data suggest that LRP,
      which bears several distinct endocytic motifs in its cytoplasmic domain, may use
      multiple pathways for endocytosis in vitro.

PMID- 16445911
TI  - Neuropilins in neoplasms: expression, regulation, and function.
AB  - Neuropilins (NRP) are membranous receptors capable of binding two disparate
      ligands, class 3 semaphorins (SEMA) and vascular endothelial growth factors
      (VEGF), and regulating two diverse systems, neuronal guidance and angiogenesis.
      The neuropilin genes, NRP1 and NRP2, share similar protein structure, but differ
      in their expression patterns, regulation, and ligand-binding specificities. NRPs
      vary in their expression patterns; for example, endothelial cells express both
      NRP1 and NRP2, lymphatic endothelial cells predominantly express NRP2, and
      epidermal cells predominantly express NRP1. NRP expression can be differentially
      regulated by transcription factors, e.g. prox-1 induces NRP2 while suppressing
      NRP1, or by growth factors, e.g. epidermal growth factor (EGF) induces NRP1 but
      not NRP2. Nearly all tumor cells express NRP1, NRP2, or both. Carcinomas express
      NRP1, whereas neuronal tumors and melanomas predominantly express NRP2. SEMAs
      play a role in neoplasms as angiogenesis inhibitors. For example, SEMA3F, which
      binds specifically to NRP2, inhibits tumor angiogenesis and metastasis.
      Metastatic tumor cells lose SEMA3F expression during progression. Therefore,
      SEMA3F may have therapeutic potential. This article focuses on the role of NRPs
      and SEMAs in tumor progression and angiogenesis.

PMID- 16445912
TI  - Exogenous antenatal glucocorticoid treatment reduces susceptibility for
      hippocampal kindled and maximal electroconvulsive seizures in infant rats.
AB  - Dexamethasone (DEX) and betamethasone (BETA) are synthetic glucocorticoids used
      clinically to reduce morbidity and mortality in infants at risk of premature
      birth. While their main role is to facilitate lung development, their effect on
      the developing nervous system and seizure susceptibility is unclear. The present
      study tested the hypothesis that antenatal DEX or BETA treatment would alter
      seizure thresholds and spread of epileptiform activity in the brains of infant
      offspring. Pregnant dams received once daily injections with DEX, BETA, or
      vehicle on gestation days 15 to 18. Physical appearance, litter size, and weight
      of the pups were assessed postnatally. Seizure thresholds were determined on
      postnatal day 14 using electroconvulsive shock delivered through ear clips (i.e.,
      generalized seizure) or kindling stimulation of the left hippocampus through
      indwelling electrodes (i.e., partial seizure). The rate of acquisition of kindled
      seizures was determined on postnatal days 14 and 15. Pups from dams treated with
      DEX and BETA were growth restricted. Antenatal BETA treatment increased seizure
      threshold for both models. Antenatal DEX treatment increased kindling threshold,
      but not electroconvulsive shock threshold. Kindling rate was unaffected by either
      antenatal treatment. In summary, repeated glucocorticoid treatments had adverse
      effects on weight, skin and litter size, raised seizure thresholds, and reduced
      seizure vulnerability. Although these effects are seemingly desirable with
      respect to seizure susceptibility, they suggest that the functional organization
      of the nervous system is altered with antenatal synthetic glucocorticoid
      treatment.

PMID- 16445913
TI  - Progesterone administration modulates AQP4 expression and edema after traumatic
      brain injury in male rats.
AB  - This study investigates whether progesterone administration regulates AQP4 and
      GFAP expression in rats with bilateral contusion injuries of the medial frontal
      cortex. Male rats were given 0 or 16 mg/kg injections of progesterone at 1, 6,
      24, and 48 h post-injury. Brains were extracted at 24 h or 72 h post-injury and
      assayed for cerebral edema and AQP4 and GFAP expression using Western blot
      analysis. Progesterone treatments reduced brain water content significantly in
      the brain-injured groups. There was no significant change in AQP4 expression 24 h
      after progesterone treatment compared to lesion + vehicle animals. However,
      progesterone significantly reduced AQP4 expression at 72 h post-injury in the
      tissue bounded by the lateral ventricles and the peri-contusion areas compared to
      lesion+ vehicle rats, but increased AQP4 expression in the tissue surrounding the
      third ventricle. Also progesterone effects on GFAP expression varied according to
      brain region. Our results can be taken to show that the expression of AQP4
      protein after TBI is time-dependent, region-specific, and possibly implicated in
      the formation and resolution of TBI-induced cerebral edema.

PMID- 16445914
TI  - The dingo non-long terminal repeat retrotransposons from the genome of the
      hookworm, Ancylostoma caninum.
AB  - Members of the retrotransposable element (RTE) clade of non-long terminal repeat
      (LTR) retrotransposon are widely distributed among eukaryote taxa, with
      representatives known from Caenorhabditis elegans, mammals, mosquitoes,
      schistosomes, and other taxa. An RTE retrotransposon has not, however, been
      characterized in detail from a parasitic nematode. Here, we characterize two
      discrete copies of an RTE-like non-LTR retrotransposon from the genome of the dog
      hookworm, Ancylostoma caninum. The elements were named dingo-1 and dingo-2. The
      full-length dingo-1 and dingo-2 elements were 3421 and 3171bp in length,
      respectively. They exhibited 54% nucleotide sequence identity to one another
      across their entire length and 40%/58% amino-acid sequence identity/similarity
      across their open reading frames. dingo-1 and dingo-2 exhibited hallmark
      structures and sequences of non-LTR retrotransposons of the RTE family including
      a single open reading frame encoding apurinic-apyrimidinic endonuclease (EN) and
      reverse transcriptase (RT), in that order. Phylogenetic analyses targeting the RT
      and the EN domains both confirmed that dingo-1 and dingo-2 were members of the
      RTE clade and that they were closely related to RTE-1 from C. elegans, to BDDF
      from Bos taurus and to SR2 from Schistosoma mansoni. Dot blot hybridization
      indicated that as many as 100-1000 copies of dingo-1 reside within the genome of
      A. caninum, while detection by RT-PCR of transcripts encoding dingo-like elements
      suggested that dingo-1 and -2 may be retrotranspositionally active within the
      genome of A. caninum. The dingo elements are the first retrotransposons to be
      characterized from a hookworm genome.

PMID- 16445915
TI  - Nuclear envelope localization of human UNC84A does not require nuclear lamins.
AB  - The SUN proteins are a conserved family of proteins in eukaryotes. Human UNC84A
      (Sun1) is a homolog of Caenorhabditis elegans UNC-84, a protein involved in
      nuclear anchorage and migration. We have analyzed targeting of UNC84A to the
      nuclear envelope (NE) and show that the N-terminal 300 amino acids are crucial
      for efficient NE localization of UNC84A whereas the conserved C-terminal SUN
      domain is not required. Furthermore, we demonstrate by combining RNA interference
      with immunofluorescence and fluorescence recovery after photobleaching analysis
      that localization and anchoring of UNC84A is not dependent on the lamin proteins,
      in contrast to what had been observed for C. elegans UNC-84.

PMID- 16445916
TI  - Finger-assisted stretching technique for cesarean section.
AB  - OBJECTIVE: To compare the perioperative outcomes of two cesarean section methods,
      the finger-assisted stretching technique (FAST), based on a modified Joel-Cohen
      method, with the traditional technique. METHODS: A retrospective review of the
      records of 416 women who underwent cesarean sections at Guro Hospital, Seoul,
      Korea, between May 1993 and December 2001 was performed. Of the 416 women, 283
      underwent cesarean sections with FAST and 133 with the traditional technique.
      RESULTS: Operative time was significantly shorter with FAST (15.3 vs. 42.6 min,
      P<.05), and FAST was associated with lower blood loss (601 vs. 928 mL, P<.05) and
      shorter hospital stay (3.7 vs. 6.5 days, P<.05). There were no significant
      differences in wound infection, voiding difficulty, and postoperative adhesions
      between the two methods. CONCLUSION: These results suggest that FAST may be the
      better technique.

PMID- 16445917
TI  - Apolipoprotein E genotype and statins affect CRP levels through independent and
      different mechanisms: AGES-Reykjavik Study.
AB  - OBJECTIVE: C-reactive protein (CRP), an inflammatory marker, was linked to
      coronary heart disease (CHD) in the Reykjavik study cohort. Recent genetic
      studies have shown that the apolipoprotein E (APOE) epsilon4 allele is associated
      with lower CRP levels. Statin treatment has also been shown to lower CRP levels.
      In the Age Gene/Environment Susceptibility (AGES)-Reykjavik Study, we examined
      the association of APOE genotypes with CRP accounting for the effect of statin
      treatment, previous CHD and a mid-life measurement of erythrocyte sedimentation
      rate (ESR), an inflammatory marker associated with risk in this cohort. METHODS
      AND RESULTS: The first 2296 participants (mean age 76+/-6 years, 42% men) in the
      AGES-Reykjavik Study were genotyped for APOE CRP concentration was measured with
      a high sensitivity method. A general linear model was used to evaluate the
      association of APOE genotype to CRP levels. The frequencies of the APOE alleles
      are epsilon2=0.06, epsilon3=0.78 and epsilon4=0.16. CRP levels ranged from 0.2 to
      56.6 mg/L, median 1.9 mg/L. Participants carrying one or two epsilon4 alleles
      have significantly lower CRP levels than non-carriers and this effect was
      observed in a dose-dependent manner. This trend is the same in users and non
      users of statin treatment. CONCLUSIONS: This study suggests that the contribution
      of the epsilon4 allele towards lowering CRP levels is independent and may be by a
      different mechanism than how statins affect inflammation.

PMID- 16445918
TI  - Analysis of the flow field induced by the sessile peritrichous ciliate
      Opercularia asymmetrica.
AB  - The feeding mechanism of the sessile protozoon Opercularia asymmetrica
      (Oligohymenophorea, Peritrichia) relies on the cilia beat generating a flow field
      that convectively transports suspended particles and dissolved substances to the
      oral cavity of the organism. By use of optical micro-flow measurement and
      theoretical methods the flow environment of two neighbouring peritrichous ciliate
      cells is studied. Both, yeast cells (Saccharomyces cerevisiae) and artificial
      flow tracers are used for the visualisation of the flow field. Artificial tracers
      are rejected by the protozoa and deviate from the fluid path lines, while yeast
      cells follow the flow almost perfectly. This is shown through a dimensional
      analysis of the involved hydrodynamic forces on the tracers. The measured flow
      field exhibits maximum velocities of 25 microm/s at around 20 microm distance
      ahead of an individual ciliate. The flow field extends 200 microm from the
      location of the ciliate. A nicking motion of the protozoon is observed and found
      not to obey any periodic law. Multiples of protozoa exhibit most commonly an
      alternating cilia beat regime generating a non-stationary flow field. It can be
      shown through theoretical methods that fluid exchange is enhanced in this
      alternating regime compared to a flow field generated by a single ciliate. Fluid
      exchange depends on the distance of the ciliates from each other and on the
      alteration frequency of the cilia beat. The comparison of an analytical Stokes'
      flow solution with the observed fluid flow serves to determine the force required
      to maintain the flow field against viscous dissipation. The force magnitude is in
      the order of magnitude of 10-100 pN.

PMID- 16445919
TI  - Novel solid-phase extraction method to separate 4-desmethyl-, 4-monomethyl-, and
      4,4'-dimethylsterols in vegetable oils.
AB  - Conventional methods for sterol fractions separation by TLC have some drawbacks
      such as low recovery and time consuming. A new solid-phase extraction (SPE)
      method was developed with stepwise elution by increasing the polarity of solvents
      mixture: n-hexane and diethyl ether. This method was applied to separate sterol
      fractions of hazelnut and virgin olive oils, and our results were compared with
      those of TLC method. The recovery of spiked authentic sample of 4
      desmethylsterols in oil was higher with the SPE method (94%) compared with the
      TLC method (62%). The amount of 4,4'-dimethylsterols and 4-desmethylsterols
      separated with SPE in both hazelnut and virgin olive oil samples were at least
      75% and 35%, respectively, higher than that of TLC. Generally, both methods
      obtained similar results for 4-monomethylsterols of the two oils. This new SPE
      method to separate phytosterol fractions was less time consuming, simpler and can
      be used instead of preparative TLC to detect adulteration of virgin olive oil
      with hazelnut oil.

PMID- 16445920
TI  - Optimization of silylation using N-methyl-N-(trimethylsilyl)-trifluoroacetamide,
      N,O-bis-(trimethylsilyl)-trifluoroacetamide and N-(tert-butyldimethylsilyl)-N
      methyltrifluoroacetamide for the determination of the estrogens estrone and
      17alpha-ethinylestradiol by gas chromatography-mass spectrometry.
AB  - This paper reports an improved silylation procedure for simultaneous
      determination of the steroid hormones 17alpha-ethinylestradiol (EE2) and estrone
      (E1) using gas chromatography-mass spectrometry (GC-MS). This follows a re
      assessment of some of the popular silylation procedures using N-methyl-N
      trimethylsilyltrifluoroacetamide (MSTFA), N-O-bis-(trimethylsilyl)
      trifluoroacetamide (BSTFA) and N-(tert-butyldimethylsilyl)-N
      methyltrifluoroacetamide (MTBSTFA), which lead to the formation of trimethylsilyl
      (TMS) and tert-butyldimethylsilyl (TBS) derivatives. Silylation of EE2 using
      MSTFA or BSTFA+1% TMCS in ethyl acetate, acetonitrile and dichloromethane
      solvents produced multiple peaks corresponding to TMS-E1, and 3-mono-TMS-EE2
      and/or 3,17-di-TMS-EE2 in variable proportions depending on the solvent used.
      When pyridine or dimethyl formamide solvents were used in the silylation of EE2
      under the same reaction conditions, only 3,17-di-TMS-EE2 derivative was formed.
      Derivatization using MTBSTFA reagents using ethyl acetate, acetonitrile,
      dichloromethane, pyridine and dimethyl formamide resulted in almost 100%
      conversion of mono-TBS-EE2 to the TBS-E1. Therefore, typical methods used in some
      previous GC-MS determinations of E1 and EE2 in environmental water and/or
      sediment samples are subject to speculation. However, we can confirm that any of
      the TMS reagents can be used with either pyridine or dimethyl formamide under
      suitable reaction conditions.

PMID- 16445921
TI  - Analytical scale purification of zirconia colloidal suspension using field
      programmed sedimentation field flow fractionation.
AB  - Sedimentation field flow fractionation was used to obtain purified fractions from
      a polydispersed zirconia colloidal suspension in the potential purpose of optical
      material hybrid coating. The zirconia particle size ranged from 50/70 nm to 1000
      nm. It exhibited a log-Gaussian particle size distribution (in mass or volume)
      and a 115% polydispersity index (P.I.). Time dependent eluted fractions of the
      original zirconia colloidal suspension were collected. The particle size
      distribution of each fraction was determined with scanning electron microscopy
      and Coulter sub-micron particle sizer (CSPS). These orthogonal techniques
      generated similar data. From fraction average elution times and granulometry
      measurements, it was shown that zirconia colloids are eluted according to the
      Brownian elution mode. The four collected fractions have a Gaussian like
      distribution and respective average size and polydispersity index of 153 nm (P.I.
      = 34.7%); 188 nm (P.I. = 27.9%); 228 nm (P.I. = 22.6%), and 276 nm (P.I. =
      22.3%). These data demonstrate the strong size selectivity of SdFFF operated with
      programmed field of exponential profile for sorting particles in the sub-micron
      range. Using this technique, the analytical production of zirconia of given
      average size and reduced polydispersity is possible.

PMID- 16445922
TI  - Estimation of aroma glycosides of nutmeg and their changes during radiation
      processing.
AB  - Glycosidically bound volatile compounds of nutmeg were identified as glyco
      conjugates of p-cymene-7-ol, eugenol, methoxyeugenol and alpha-terpineol. Using
      phenyl-beta-glucoside as external standard the contents of these glycosidic
      precursors were estimated based on the measurement of TLC spot density on a
      densitometer. p-Cymene-7-ol rutinoside was the major aroma glycoside (3.15 mg/100
      g), followed by glucosides of methoxyeugenol (0.61 mg/100 g), eugenol (0.50
      mg/100 g) and alpha-terpineol (0.51 mg/100 g). A dose-dependent breakdown of
      these glycosidic precursors was observed during gamma-radiation processing. Among
      the four glycosides, alpha-terpineol glucoside was the most sensitive to
      radiation while p-cymene-7-ol rutinoside was the least sensitive. A reduction in
      the content of total glycosides by almost 50% was noted at a dose of 5kGy.
      Partitioning of aroma glycoside into n-butanol from aqueous extracts was found to
      result in rapid isolation of aroma glycosides, avoiding time consuming pre
      purification on Amberlite XAD-2 column. A routine method based on extraction into
      n-butanol and subsequent quantification of post-irradiation changes in aroma
      glycosides on a TLC plate using a densitometer is proposed.

PMID- 16445923
TI  - Preparation of a new doubly tethered chiral stationary phase based on (+)-(18
      crown-6)-2,3,11,12-tetracarboxylic acid and its application.
AB  - A new doubly tethered chiral stationary phase (CSP) based on (+)-(18-crown-6)
      2,3,11,12-tetracarboxylic acid was prepared by attaching the second tethering
      group to silica gel through a carbon atom of the first tethering group of the
      corresponding singly tethered CSP, which was previously developed in our
      laboratory. The new doubly tethered CSP was applied successfully to the
      resolution of various racemic alpha-amino acids, amines and amino alcohols
      containing a primary amino group. In most cases, the chiral recognition
      efficiency of the new doubly tethered CSP was superior to that of the
      corresponding singly tethered one in the resolution of alpha-amino acids, amines
      and amino alcohols. In the resolution of some racemic primary amino compounds,
      the new doubly tethered and the corresponding singly tethered CSPs were
      complementary with each other. The chiral resolution behaviors on the new doubly
      tethered CSP were examined with the variation of the type and content of organic
      and acidic modifiers in aqueous mobile phase and the column temperature. The
      chiral resolution behaviors on the new doubly tethered CSP were generally quite
      similar to those on the corresponding singly tethered CSP. The stability of the
      new doubly tethered CSP was greater than that of the corresponding singly
      tethered CSP.

PMID- 16445924
TI  - Planar chromatographic analysis and quantification of short-lived radioactive
      metabolites from microdialysis fractions.
AB  - A sensitive radiochromatographic method for the quantitative determination of
      compounds labelled with short-lived beta-emitting radionuclides in
      microdialysates is described. The method is well suited for microdialysis (MD)
      samples, which have small volumes and low concentrations of compounds. An 18F
      labelled (beta+; T(1/2)=109.8 min) radiopharmaceutical, (1R,2S)-4
      [18F]fluorometaraminol (FMR), was injected intravenously into rats, and
      microdialysis fractions were then collected from the blood at 15 min intervals.
      Fractions were analyzed for FMR and its radioactive metabolites by planar
      chromatography combined with digital photostimulated luminescence
      autoradiography. The lowest detectable 18F-radioactivity was 0.24 Bq/application
      and the limit of quantification was 0.31 Bq/application with 4-16 h exposure. The
      method was found to be highly sensitive and linear in the range of 0.1 Bq-2 kBq.
      This method thus allows the quantification of beta-emitting radiopharmaceuticals
      in sequential microdialysis fractions with good time-resolution.

PMID- 16445925
TI  - Normal-phase chiral liquid chromatography-mass spectrometry of non-UV-active
      compounds: applications for pharmaceutically relevant racemates.
AB  - Mixtures of hexane-like ethoxynonafluorobutane with alcohols were used as MS
      friendly mobile phases for separation and efficient detection of non-UV-active
      enantiomers and diastereomers using normal-phase HPLC-APCI-MS. Racemic muscone,
      camphorsulfonamide, camphorsultam, BOC-protected 1-(3-aminopropyl)-2-pipecoline
      and diastereomeric 2-methylhexanoyl camphorsultams were resolved on Chiralpak AS
      and AD and achiral Luna CN columns. The responses of UV and APCI-MS detectors
      were compared under separation conditions studied, with MS detection achieving
      lowest detectable quantity in the range of 0.5-2 ng per chromatographic peak. The
      absolute configuration of crystalline derivatives of racemic 2-methylhexanoic
      acid with (S)-(-)-2,10-camphorsultam was determined by X-ray analysis after their
      automatic purification by preparative LC-MS. The technique described can be used
      to purify and determine the absolute stereochemistry of compounds of unknown
      structure which contain free carboxy group and lack sufficient UV absorbance.

PMID- 16445926
TI  - Multimilligram enantioresolution of low-solubility xanthonolignoids on
      polysaccharide chiral stationary phases using a solid-phase injection system.
AB  - Kielcorins are xanthonolignoids with protein kinase C inhibition and antitumor
      activities. Four racemates were enantioresolved at a multimilligram scale on tris
      3,5-dimethylphenylcarbamate amylose phase using polar organic conditions as
      mobile phase. The low-solubility of these compounds conditioned the injection
      amount and consequently the productivity. A solid-phase injection system was
      developed to increase the production rate of the semipreparative process. The
      effects of the racemates and the related enantiomers on the in vitro growth of
      human breast cancer cell line MCF-7 were compared. Differences in their growth
      inhibitory activity were observed.

PMID- 16445927
TI  - Multiresidue liquid chromatography tandem mass spectrometry determination of 52
      non gas chromatography-amenable pesticides and metabolites in different food
      commodities.
AB  - A multiresidue method is developed for the screening, quantification and
      confirmation of 43 pesticides, belonging to different chemical families of
      insecticides, acaricides, fungicides, herbicides and plant growth regulators, and
      9 pesticide metabolites in four fruit and vegetable matrices. Pesticide residues
      are extracted from the samples with MeOH:H2O (80:20, v/v) 0.1% HCOOH, and then a
      cleanup step using OASIS HLB SPE cartridges is applied. The SPE eluate is
      concentrated and the final volume adjusted to 1 mL with MeOH:H2O (10:90, v/v)
      before injection into LC-MS/MS. Analyses are performed using electrospray
      ionization (ESI) and triple quadrupole (QqQ) analyzer. The method has been
      validated based on the SANCO European Guidelines for representative samples that
      were chosen to study the influence of different matrices: high water content
      (tomato), high acidic content (lemon), high sugar content (raisin) and high
      lipidic content (avocado). Special attention has been given to minimize the
      degradation of some pesticides into their metabolites and the losses observed in
      the evaporation step. Under the optimized conditions, the recoveries were, with a
      few exceptions, in the range 70-110% with satisfactory precision (CV < or = 15%).
      The quantification of analytes was carried out using the most sensitive
      transition for every compound and by "matrix-matched" standards calibration. The
      method can be used for the accurate determination of 52 pesticides and
      metabolites in one single determination step at the 0.01 mg/kg level.
      Confirmation of residues detected in samples is performed by an independent
      injection into the LC-MS/MS system by acquiring additional MS/MS transitions to
      that used for quantification. The acquisition of the highest number of available
      transitions is suggested for unequivocal confirmation of the analyte.

PMID- 16445928
TI  - Electrokinetic migration across artificial liquid membranes. New concept for
      rapid sample preparation of biological fluids.
AB  - Basic drug substances were transported across a thin artificial organic liquid
      membrane by the application of 300 V d.c. From a 300 microl aqueous donor
      compartment (containing 10 mM HCl), the drugs migrated through a 200 microm
      artificial liquid membrane of 2-nitrophenyl octyl ether immobilized in the pores
      of a polypropylene hollow fiber, and into a 30 microl aqueous acceptor solution
      of 10 mM HCl inside the lumen of the hollow fiber. The transport was forced by an
      electrical potential difference sustained over the liquid membrane, resulting in
      electrokinetic migration of drug substances from the donor compartment to the
      acceptor solution. Within 5 min of operation at 300 V, pethidine, nortriptyline,
      methadone, haloperidol, and loperamide were extracted with recoveries in the
      range 70-79%, which corresponded to enrichments in the range 7.0-7.9. The
      chemical composition of the organic liquid membrane strongly affected the
      permeability, and may serve as an efficient tool for controlling the transport
      selectivity. Water samples, human plasma, and human urine were successfully
      processed, and in light of the present report, electrokinetic migration across
      thin artificial liquid membranes may be an interesting tool for future isolation
      within chemical analysis.

PMID- 16445929
TI  - Application of dual counter-current chromatography for rapid sample preparation
      of N-methylcarbamate pesticides in vegetable oil and citrus fruit.
AB  - Dual counter-current chromatography (dual CCC) has been successfully applied to
      rapid sample preparation for the simultaneous determination of residual carbaryl,
      fenobucarb and methomyl in vegetable oil and citrus fruit. The citrus fruit
      samples were extracted with n-hexane solution containing stable isotopically
      labeled internal standards (methomyl-d3, fenobucarb-d3 and carbaryl-d9), and
      applied to dual CCC using a two-phase solvent system of n-hexane-acetonitrile to
      purify the carbamate pesticides from aliphatic sample matrix. The coiled column
      was rotated at 420 rpm, the lower mobile phase was introduced through the head
      toward the tail, and the upper mobile phase in the opposite direction. Due to the
      high partition efficiency of dual CCC, the lower phase fraction collected from 2
      to 5 min after injection could be subjected to flow-injection tandem mass
      spectrometry directly after concentration. Repetitive sample injection can be
      performed at high reproducibility without a risk of contamination from the
      compounds retained in the column.

PMID- 16445930
TI  - A stability indicating assay method for cefuroxime axetil and its application to
      analysis of tablets exposed to accelerated stability test conditions.
AB  - Cefuroxime axetil is the esterified form of cefuroxime, injectable second
      generation cephalosporine antibiotic that can be given orally. Stereo and
      structural isomers of cefuroxime axetil (CA), anti-cefuroxime axetil (ACA) and
      Delta(3)-cefuroxime axetil (DCA), can be present in cefuroxime dosage forms as
      the process related impurities as well as possible degradation product. Sensitive
      and precise reversed-phase high-performance liquid chromatography (RP-HPLC)
      method was developed and validated for the determination of cefuroxime axetil in
      the presence of its degradation products in solid dosage forms. The RSD values
      for cefuroxime axetil, anti-cefuroxime axetil and Delta(3)-cefuroxime axetil of
      1.80, 1.99 and 2.48%, respectively, indicated a good precision of the RP-HPLC
      method. Developed RP-HPLC method was sensitive with LOD = 0.08 microg mL(-1) and
      LOQ = 0.60 microg mL(-1) for anti-cefuroxime axetil and LOD = 0.06 microg mL(-1)
      and LOQ = 0.45 microg mL(-1) for Delta(3)-cefuroxime axetil. Holding studies were
      carried out on Ceroxim tablets, according to ICH regulation at 30 degrees C/60%
      relative humidity (RH) and 40 degrees C/75% RH for 1, 2, 3 and 6 months. The
      review data from the stability studies conducted, show the significant content
      change of Delta(3)-cefuroxime axetil.

PMID- 16445931
TI  - Development of a polar-embedded stationary phase with unique properties.
AB  - This paper describes a new polar-embedded stationary phase that contains an
      internal sulfonamide functional group coupled with an ether linkage. The
      synthesis involves functionalization of spherical silica particles with ligands
      prepared in a multi-step synthesis. The resulting material contains 16.5% carbon,
      corresponding to a ligand coverage of 2.4mumol/m(2). Chromatographic evaluations
      indicates that the new stationary phase exhibits lower polarity than any other
      polar-embedded packings investigated, with additional features such as low
      silanol activity, excellent compatibility with 100% aqueous mobile phases, higher
      shape selectivity for polycyclic aromatic hydrocarbons, and strong affinity to
      nitro-containing compounds.

PMID- 16445932
TI  - Concentration of hydrogen nanobubbles in electrolyzed water.
AB  - The hydrogen concentration of solutions supersaturated with hydrogen comprising
      dissolved hydrogen and hydrogen bubbles obtained through water electrolysis was
      studied. The rate of decrease in concentration of hydrogen nanobubble diameter
      below 600 nm and dissolved hydrogen with elapsed time after electrolysis was
      seemed to be independent of ionic strength and ion type and storage temperature.
      The concentration of hydrogen nanobubbles (mol dm(-3)) in electrolyzed water
      decreases with ionic strength, while the total hydrogen concentration remains
      roughly constant. The hydrogen nanobubble concentration increases in accordance
      with the nature of ions existing in solution in the following order I- < Br- < Cl
      and K+ < Li+ < Na+. It is shown that the ratio of hydrogen nanobubble
      concentration to total hydrogen concentration of hydrogen in a catholyte strongly
      depends on the ratio in the supersaturated hydrogen solution near the electrode
      surface.

PMID- 16445933
TI  - Kinetic estimation of the adsorbate distribution on the surface from adsorbed
      amounts.
AB  - A phenomenological multilayer adsorption model for a well-dispersed, homogeneous,
      nonporous adsorbent and a molecular adsorbate is presented. The model provides
      explicit kinetic expressions associating the adsorbed amounts to the fraction of
      the surface occupied and reduces to the first- and second-order adsorption models
      for special cases. Parameters of the model are a pair of true rate constants
      related to the adsorbate-adsorbent and adsorbate-surface adsorbate affinities. A
      general graphical procedure and analytical equations for special cases are
      provided to estimate the rate constants from kinetic adsorption data. Data from
      the adsorption of sodium stearate onto alpha-alumina from water were used to test
      the model. The predicted values of the rate constants suggested that the stearate
      was distributed homogeneously on the alumina surface and essentially adsorbed as
      a monolayer before starting to form the second layer.

PMID- 16445934
TI  - Study of properties of modified silicones at solid-liquid interface: fabric
      silicone interactions.
AB  - Silicones are special reagents that impart desired surface properties such as
      softness, bounciness and antiwrinkle properties to fabrics and related materials.
      Although these finishing processes have been practiced routinely, very little is
      known about the mechanisms involved in modification so that they could be
      improved. The current study was undertaken to develop basic understanding of the
      mechanisms responsible for surface modification of fibers using silicones. PDMS
      based amino silicone emulsions, quaternized to various degrees using dimethyl
      sulphate, were used in the present study. The electrokinetic properties of the
      modified silicones were studied as a function of pH. It was expected that the
      silicone emulsions would show a steady positive zeta potential throughout the pH
      range due to the quaternization by dimethyl sulphate. Surprisingly, a sudden drop
      in the zeta potential was observed around pH 8 with the samples turning hazy in
      the pH range of 8-10. Turbidimetric studies also showed a sudden increase in the
      turbidity in the pH range 8-10 where commercial processes also encounter
      problems. It was concluded that the emulsions were destabilized at pH 8-10 thus
      rendering them ineffective for surface treatment. In order to identify reason for
      the improvement in fabric properties, fiber structure was monitored using atomic
      force microscopy. It was observed that the treated fibers were far smoother,
      relaxed and uniform as compared to the untreated fibers. Thus the morphology of
      the fabric is modified in a specific way by treatment with specialty silicones.

PMID- 16445935
TI  - Application to immunoassays of the fusion protein between protein ZZ and enhanced
      green fluorescent protein.
AB  - Enhanced green fluorescent protein (EGFP) from Aequorea victoria was fused to the
      C terminal region of protein ZZ, an artificial synthetic IgG Fc fragment binding
      protein derived from tandem repeats of the B domain of protein A. The ZZ-EGFP
      fusion protein was expressed in Escherichia coli with a His(6) tag and purified
      in high yield by one-step Ni(2+) chelating affinity chromatography. It was then
      used in the immunoblot analysis of GST and TNFalpha as well as in
      immunofluorescent assays of 293T cells transfected with IRF3, an interferon
      regulatory factor which localized in cytoplasm without virus infection. The
      fusion protein also performed effectively in FACS analysis of surface integrin
      beta3 subunit on 293 T cells. The chimeric protein bound various antibodies from
      different animal sources, directed against a variety of proteins. Thus, ZZ-EGFP
      showed broad promise in potential immunological applications.

PMID- 16445936
TI  - The effects of Calliphora vomitoria Tachykinin-I and the FMRFamide-related
      peptide Perisulfakinin on female Phormia regina crop contractions, in vitro.
AB  - The dipteran crop is an elaborate diverticulation of the foregut that serves as
      an important food reservoir and feeding regulator. Peptidergic innervation has
      been associated with the crop of the blow fly Phormia regina and myotropic
      neuropeptides have been previously demonstrated to affect crop contraction rates,
      in vitro. The blow fly peptide, callitachykinin-1 was found to increase the rate
      of contractions and alter the contractile morphology of the P. regina crop, in
      vitro. The cockroach peptide perisulfakinin, however, had no measurable affect on
      crop contractions.

PMID- 16445937
TI  - Prevalence and seasonality of Ascogregarina culicis (Apicomplexa: Lecudinidae) in
      natural populations of Aedes aegypti (Diptera: Culicidae) from temperate
      Argentina.
AB  - Ascogregarina infections from South America were recently documented in Brazil
      and Argentina. The aim of this study was to report our recent findings on the
      prevalence and seasonality of Ascogregarina culicis in Aedes aegypti adults from
      temperate Argentina. Between December 2003 and May 2005, 391 females of Ae.
      aegypti were captured in two areas of Greater Buenos Aires. Overall prevalence of
      A. culicis was 21.2% (83/391), and a significant difference was observed between
      both areas (28.4% vs. 8%). Infected Ae. aegypti were found from November to May,
      with highest values in March (24-37%). Parasite prevalence and host abundance
      showed similar seasonal patterns. Our observations suggest a widespread
      infestation of A. culicis among Ae. aegypti populations from temperate Argentina.

PMID- 16445938
TI  - Partial replacement of cardiac troponin I with a non-phosphorylatable mutant at
      serines 43/45 attenuates the contractile dysfunction associated with PKCepsilon
      phosphorylation.
AB  - We have previously reported a transgenic mouse that over-expresses constitutively
      active PKCepsilon in the myocardium and exhibits a steady progression to heart
      failure. Associated with the decline in function was an increased phosphorylation
      of sarcomeric proteins including cardiac troponin I (cTnI). To determine whether
      PKCepsilon phosphorylation of cTnI is sufficient to induce cardiac maladaptation,
      we have generated a double transgenic mouse (DbTG) that expresses constitutively
      active PKCepsilon and cTnI harboring non-phosphorylatable mutations in the
      putative PKC phosphorylation sites (S43A, S45A). We compared the hemodynamic and
      biochemical properties of the hearts from the DbTG mice to the non-transgenic and
      single transgenic lines at both 3 and 12 months of age. While no significant
      differences in LV function were noted in 3-month groups, the depression of
      function in the PKCepsilon mice was attenuated in the double transgenic mice at
      12 months. The improvement in cardiac function was correlated with decreased beta
      myosin heavy chain and ANF mRNA expression in the 12m DbTG mice. The extent of
      cTnI phosphorylation was determined using a novel one-dimensional, non
      equilibrium isoelectric focusing technique. At 3 months the migration of cTnI
      phospho-species was different in the PKCepsilon mice and to a lesser degree in
      the DbTG compared to all other groups. At 12 months additional phospho-species
      were observed in both the PKCepsilon and DbTG samples, along with an overall
      shift in the distribution of phospho-species in all groups due to age. These
      results suggest that phosphorylation of cTnI by PKCepsilon is associated with
      contractile dysfunction and partial replacement of serines 43/45 improves cardiac
      performance. Therefore, we conclude that phosphorylation of cTnI at Ser 43 and 45
      may contribute to the progression of failure.

PMID- 16445939
TI  - The dimerization mechanism of LIS1 and its implication for proteins containing
      the LisH motif.
AB  - Miller-Dieker lissencephaly, or "smooth-brain" is a debilitating genetic
      developmental syndrome of the cerebral cortex, and is linked to mutations in the
      Lis1 gene. The LIS1 protein contains a so-called LisH motif at the N terminus,
      followed by a coiled-coil region and a seven WD-40 repeat forming beta-propeller
      structure. In vivo and in vitro, LIS1 is a dimer, and the dimerization is
      mediated by the N-terminal fragment and is essential for the protein's biological
      function. The recently determined crystal structure of the murine LIS1 N-terminal
      fragment encompassing residues 1-86 (N-LIS1) revealed that the LisH motif forms a
      tightly associated homodimer with a four-helix antiparallel bundle core, while
      the parallel coiled-coil situated downstream is stabilized by three canonical
      heptad repeats. This homodimer is uniquely asymmetric because of a distinct kink
      in one of the helices. Because the LisH motif is widespread among many proteins,
      some of which are implicated in human diseases, we investigated in detail the
      mechanism of N-LIS1 dimerization. We found that dimerization is dependent on both
      the LisH motif and the residues downstream of it, including the first few turns
      of the helix. We also have found that the coiled-coil does not contribute to
      dimerization, but instead is very labile and can adopt both supercoiled and
      helical conformations. These observations suggest that the presence of the LisH
      motif alone is not sufficient for high-affinity homodimerization and that other
      structural elements are likely to play an important role in this large family of
      proteins. The observed lability of the coiled-coil fragment in LIS1 is most
      likely of functional importance.

PMID- 16445940
TI  - Molecular determinants for substrate specificity of the ligand-binding protein
      OpuAC from Bacillus subtilis for the compatible solutes glycine betaine and
      proline betaine.
AB  - Compatible solutes play a decisive role in the defense of microorganisms against
      changes in temperature and increases in osmolarity in their natural habitats. In
      Bacillus subtilis, the substrate-binding protein (SBP)-dependent ABC-transporter
      OpuA serves for the uptake of the compatible solutes glycine betaine (GB) and
      proline betaine (PB). Here, we report the determinants of compatible solute
      binding by OpuAC, the SBP of the OpuA transporter, by equilibrium binding studies
      and X-ray crystallography. The affinity of OpuAC/GB and OpuAC/PB complexes were
      analyzed by intrinsic tryptophan fluorescence and the K(D) values were determined
      to be 17(+/-1)microM for GB and 295(+/-27)microM for PB, respectively. The
      structures of OpuAC in complex with GB or PB were solved at 2.0 A and 2.8 A,
      respectively, and show an SBP-typical class II fold. The ligand-binding pocket is
      formed by three tryptophan residues arranged in a prism-like geometry suitable to
      coordinate the positive charge of the trimethyl ammonium group of GB and the
      dimethyl ammonium group of PB by cation-pi interactions and by hydrogen bonds
      with the carboxylate moiety of the ligand. Structural differences between the
      OpuAC/GB and OpuAC/PB complexes occur within the ligand-binding pocket as well as
      across the domain-domain interface. These differences provide a structural
      framework to explain the drastic differences in affinity of the OpuAC/GB and
      OpuAC/PB complexes. A sequence comparison with putative SBP specific for
      compatible solutes reveals the presence of three distinct families for which the
      crystal structure of OpuAC might serve as a suitable template to predict the
      structures of these putative compatible solute-binding proteins.

PMID- 16445941
TI  - A focused antibody library for improved hapten recognition.
AB  - The topography of the antigen-binding site as well as the number and the
      positioning of the antigen contact residues are strongly correlated with the size
      of the antigen with which the antibody interacts. On the basis of these
      considerations, we have designed a focused scFv repertoire biased for haptens,
      designated the cavity library. The hapten-specific scFv, FITC8, was used as a
      scaffold for library construction. FITC8, like other hapten binders, displays a
      characteristic cavity in its paratope into which the hapten binds. In five of the
      six complementarity-determining regions, diversity-carrying residues were
      selected rationally on the basis of a model structure of FITC8 and on known
      antibody structure-function relationships, resulting in variation of 11 centrally
      located, cavity-lining residues. L3 was allowed to carry a more complex type of
      diversity. In addition, length variation was introduced into H2, as longer
      versions of this loop have been shown to correlate with increased hapten binding.
      The library was screened, using phage display, against a panel of five different
      haptens, yielding diverse and highly specific binders to four of the antigens.
      Parallel selections were performed with a library having diversity spread onto a
      greater area, including more peripherally located residues. This resulted in the
      isolation of binders, which, in contrast to the clones selected from the cavity
      library, were not able to bind to the soluble hapten in the absence of the
      carrier protein. Thus, we have shown that by focusing diversity to the hotspots
      of interaction a library with improved hapten-binding ability can be created. The
      study supports the notion that it is possible to create antibody libraries that
      are biased for the recognition of antigens of pre-defined size.

PMID- 16445942
TI  - Hippocampal volume in aging combat veterans with and without post-traumatic
      stress disorder: relation to risk and resilience factors.
AB  - OBJECTIVE: To examine whether there are post-traumatic stress disorder (PTSD)
      related differences in hippocampal volume in middle-aged and elderly veterans and
      to examine the relationship of neuroendocrine activity, memory performance, and
      measures of risk and resilience for PTSD to hippocampal volume in this cohort.
      METHODS: Seventeen veterans with chronic PTSD and 16 veterans without chronic
      PTSD received an MRI scan followed by neuroendocrine assessment (24-h urinary
      cortisol excretion and the lysozyme IC(50-DEX), a measure of glucocorticoid
      receptor (GR) responsiveness), and cognitive testing. RESULTS: Veterans with PTSD
      did not differ from those without PTSD in hippocampal volume, but they did show
      significantly lower urinary cortisol levels, and poorer memory performance on the
      Wechsler Logical Memory test and Digit Span test. Smaller left hippocampal
      volumes were observed in veterans who developed PTSD in response to their first
      reported traumatic exposure, compared to veterans who had first experienced a
      traumatic event to which they did not develop PTSD, prior to experiencing a
      subsequent event that led to PTSD. In contrast, the two neuroendocrine measures
      were associated with risk factors related to early trauma exposure. CONCLUSION:
      Although hippocampal volume was not found to differ between subjects with and
      without PTSD, smaller hippocampal volumes in PTSD may be associated with specific
      risk and resilience factors. These may be distinct from vulnerability markers
      associated with increased responsiveness to glucocorticoids and/or other
      neuroendocrine measures that have been observed in combat-related PTSD.

PMID- 16445943
TI  - Could steroids mask the diagnosis of cerebrotendinous xanthomatosis?
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of
      bile acid synthesis, caused by impaired hydroxylation of cholesterol side chains
      due to deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1),
      leading to accumulation of cholestanol and cholesterol in brain and other
      tissues. Elevated plasma cholestanol serves as a key marker for the clinical
      diagnosis of CTX. In the present report we describe a young man with CTX who was
      on high dose steroids for a misdiagnosed chronic inflammatory demyelinating
      polyneuropathy (CIDP) and had normal level of serum cholestanol. When steroids
      were discontinued, markedly elevated serum cholestanol was measured concomitant
      with marked clinical worsening. This observation may imply that steroids can
      lower plasma cholestanol, possibly by directly inducing residual CYP27A1 activity
      or by inducing alternative pathways for cholestanol elimination.

PMID- 16445944
TI  - The sources of thermal energy exchange accompanying microbial catabolism.
AB  - Calculations are made of thermal energy exchanges from catabolic reactions in the
      aqueous state, using thermodynamic properties at 0.001 M, indicated by subscript
      "(B)". Heats of reaction are calculated as
      DeltarHB,298.15o'=DeltarXB,298.15o'+DeltarQab,B,298.15o' (1), or as
      DeltarHB,298.15o'=DeltarGB,298.15o'+TDeltarSB,298.15o' (2), where
      DeltarXo'B,298.15 and DeltarGo'B,298.15 represent non-thermal, chemical energy
      converted into thermal energy during a reaction and where
      DeltarQab,B,298.15o'andTDeltarSB,298.15o' represent the exchange of absorbed
      thermal energy as reactants become converted into products. Percentages are
      tabulated of the thermal energy exchanges contributed to DeltarHB,298.15o' by
      DeltarXB,298.15o' and DeltarQab,B,298.15o', and by DeltarGB,298.15o' and
      TDeltarSB,298.15o'. Aerobically, for substrates not containing nitrogen, the
      value of DeltarXB,298.15o' averages 4.21% more negative than that of
      DeltarGB,298.15o'. For substrates containing nitrogen this average drops to
      1.80%. For substances not containing nitrogen, the thermal energy contributed by
      DeltarQab,B,298.15o' to DeltarHB,298.15o' averages 2.21%, whereas that
      contributed by TDeltarSB,298.15o' averages -1.95%. The difference is 4.16%, which
      is close to the average value of 4.21% that DeltarXB,298.15o' is more negative
      than DeltarGB,298.15o'. This observation indicates that the difference between
      DeltarXB,298.15o' and DeltarGB,298.15o' is due almost entirely to the manner in
      which exchanges in absorbed thermal energies are measured or calculated for the
      reaction systems studied. The same applies to the oxidation of substances
      containing nitrogen. Here, the thermal energy contributed to DeltarHB,298.15o' by
      DeltarQab,B,298.15o' averages 5.32%, whereas that contributed by
      TDeltarSB,298.15o' averages 3.50%. The difference between them is 1.82%, which is
      close to the average value of 1.80% that DeltarXB,298.15o' is more negative than
      DeltarGB,298.15o'. Anaerobically, for the processes tested fewer inferences could
      be drawn. The values of DeltarGB,298.15o' are much more negative than those of
      DeltarXB,298.15o' in three examples out of five and widely variable, quite the
      opposite of the data on the aerobic processes. One anaerobic DeltarXB,298.15o'
      value is positive, indicating that something other than the total free energy
      change must be driving this particular process.

PMID- 16445945
TI  - Sustainable ecosystem management using optimal control theory: part 2 (stochastic
      systems).
AB  - Sustainable development of ecosystems through external ecosystem management is
      assuming importance for the environmentalists. To that effect, previous work by
      the authors looked at the option of manipulating population dynamics of the
      species in an ecosystem to achieve sustainability. Fisher information is used as
      the quantifying measure of sustainability and optimal control theory is used to
      derive the control profiles. However, that work considered only deterministic
      systems. Uncertainty being prevalent in all systems, particularly in natural
      systems, this paper extends that work to analyse uncertain systems. Predator-prey
      models are used to model the species populations and different control
      philosophies are compared. Ito mean reverting process is used to model the
      stochastic process, and stochastic maximum principle is used to derive the
      control profiles. The results for the objective of FI variance minimization
      qualitatively agree with those for the deterministic system, while the results
      for the FI maximization objective differ. It is observed that the instability
      associated with the FI maximization objective for deterministic systems is
      absorbed by the noise introduced by the uncertainty. Quantitatively, it is
      observed that the degree of uncertainty, along with its presence, is also
      important to identify the most appropriate management strategy.

PMID- 16445946
TI  - Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer
      applications.
AB  - Can drinking several cups of green tea a day keep the doctor away? This certainly
      seems so, given the popularity of this practice in East Asian culture and the
      increased interest in green tea in the Western world. Several epidemiological
      studies have shown beneficial effects of green tea in cancer, cardiovascular, and
      neurological diseases. The health benefits associated with green tea consumption
      have also been corroborated in animal studies of cancer chemoprevention,
      hypercholesterolemia, artherosclerosis, Parkinson's disease, Alzheimer's disease,
      and other aging-related disorders. However, the use of green tea as a cancer
      chemopreventive or for other health benefits has been confounded by the low oral
      bioavailability of its active polyphenolic catechins, particularly
      epigallocatechin-3-gallate (EGCG), the most active catechin. This review
      summarizes the purported beneficial effects of green tea and EGCG in various
      animal models of human diseases. Dose-related differences in the effects of EGCG
      in cancer versus neurodegenerative and cardiovascular diseases, as well as
      discrepancies between doses used in in vitro studies and achievable plasma
      understanding of the in vivo effects of green tea catechins in humans, before the
      use of green tea is widely adopted as health-promoting measure.

PMID- 16445947
TI  - Epigallocatechin gallate reduces hypoxia-induced apoptosis in human hepatoma
      cells.
AB  - Cell detachment from extracellular matrix is closely related to induction of
      apoptosis. Epigallocatechin gallate (EGCG) has been shown to have antioxidant
      effect and to protect hypoxia-induced damage. We investigated whether EGCG
      reduced hypoxia-induced apoptosis and cell detachment in HepG2 cells. EGCG
      prevented cell death by hypoxia (0.5% O2) in a dose-dependent manner (hypoxic
      cell viability, 54.67%). RT-PCR and caspase3 activity assay showed that the
      hypoxia-induced cell death was caused by apoptosis increasing mRNA level of BAX,
      CASP3, and caspase3 activity. EGCG reduced increase of these mRNA and caspase3
      activity. Western blot analysis and immunocytochemistry showed that EGCG
      increased cell adhesion proteins including E-cadherin (CDH1), tumor-associated
      calcium signal transducer 1 (TACSTD1), and protein tyrosine kinase 2 (PTK2)
      decreased by hypoxia. Hypoxia-induced apoptosis in HepG2 cells, and EGCG
      contributed to the HepG2 cell survival by attenuating the apoptosis.

PMID- 16445948
TI  - Cardiovascular oxidative stress is reduced by an ACE inhibitor in a rat model of
      streptozotocin-induced diabetes.
AB  - Blockade of the renin-angiotensin system (RAS) reduces cardiovascular morbidity
      and mortality in diabetic patients. Ang II-mediated generation of reactive oxygen
      species (ROS) has been suggested to be involved in several diabetic
      complications. We investigated whether the inhibition of Ang II production with
      an ACE inhibitor (ACEi) reduces oxidative stress and limits structural
      cardiovascular remodeling in a rat model of streptozotocin (STZ)-induced
      diabetes. Diabetic rats were treated for 7 weeks with an ACEi (lisinopril, 5
      mg/kg/d), an antioxidant (N-acetyl-l-cysteine (NAC), 0.5 g/kg/d) and their
      combination. At sacrifice, ROS in the myocardium and thoracic aorta, LV myocyte
      number and size and aorta morphology were determined by quantitative histological
      methods. Superoxide and hydroxyl radical content, detected by dihydroethidium
      (DHE) and 8-hydroxydeoxyguanosine (8-OHdG), were 6.7 and 4.5-fold, respectively,
      higher in diabetic myocardium than in non-diabetic controls (p<0.001). The amount
      of superoxide was 5-fold higher in the thoracic aorta of diabetic rats compared
      to controls (p<0.001). Diabetes caused a modest increase in myocyte volume (+13%,
      p<0.01), a reduction of LV myocyte number (-43%, p<0.001), an accumulation of
      collagen around coronary arterioles (1.9-fold increase, p<0.01) and a decrease in
      arterial elastin/collagen ratio (-63%, p<0.001) compared to controls. Treatment
      with the ACEi attenuated ROS formation and prevented phenotypic changes in the
      heart (cardiomyocyte hypertrophy, perivascular fibrosis) and in the aorta of
      diabetic rats to the same extent as NAC. The absence of an additive effect,
      suggests a common mechanism of action, through the reduction of oxidative stress.

PMID- 16445949
TI  - Inhibition of telomerase activity and induction of apoptosis by curcumin in K-562
      cells.
AB  - Telomerase, a reverse transcriptase that maintains telomere length, is highly
      activated in tumor cells and practically absent in somatic cells and hence
      considered a potential marker for tumorigenesis. A connection between telomerase
      activity and resistance to apoptosis has been established. Telomerase, therefore,
      has been proposed to represent a novel and potentially selective target for
      cancer therapy. Several synthetic compounds have been developed in recent years
      with a view to inhibit telomerase activity with telomere shortening below a
      critical length resulting in apoptosis. Such compounds are always highly toxic.
      Many plant-derived products act through the induction of apoptosis as a mechanism
      to suppress carcinogenesis. Curcumin, a phenolic compound isolated from the
      rhizome of the plant Curcuma longa Linn., has been reported to possess anti
      tumor, apoptotic and anti-angiogenic properties. Apoptosis has emerged as the
      major mechanism by which anti-tumor agents eliminate pre-neoplastic cells or
      cells progressed to malignancy. The present study was undertaken to examine the
      mechanism of curcumin-induced apoptosis in human leukemia cell line K-562 with
      particular emphasis on the role of curcumin on telomerase activity. Induction of
      apoptosis by curcumin is initiated by the release of cytochrome c from
      mitochondria into the cytosol, and evidenced by the increase in DNA content in
      the sub-G1 region as obtained from FACS analysis. Apoptosis is mediated by the
      activation of caspases 3 and 8, up-regulation of the apoptotic gene bax with
      concomitant down-regulation of the anti-apoptotic gene bcl-2. Using TRAP assay it
      has been observed that curcumin inhibits telomerase activity in a dose and time
      dependent manner, the inhibition being due to suppression of translocation of
      telomerase reverse transcriptase (TERT), a catalytic subunit, from cytosol to
      nucleus. Most significantly, the inhibition of telomerase activity by curcumin
      correlates with several parameters of apoptosis. The results suggest that
      telomerase status plays an important role in the induction of apoptosis in K-562
      cells by curcumin.

PMID- 16445950
TI  - The acetylcholinesterase inhibitor, Donepezil, regulates a Th2 bias in
      Alzheimer's disease patients.
AB  - The increased pro-inflammatory cytokine production was previously observed in
      Alzheimer's disease (AD). We sought to explore whether acetylcholinesterase
      inhibitor (AChEI) therapy ameliorates clinical symptoms in AD through down
      regulation of inflammation. Expression and release of monocyte chemotactic
      protein-1 (MCP-1), a positive regulator of Th2 differentiation, and interleukin
      (IL)-4, an anti-inflammatory cytokine from peripheral blood mononuclear cells
      (PBMC) in AD patients, were investigated. PBMC were purified from AD patients at
      time of enrollment (T0) and after 1 month of treatment with AChEI (T1) and from
      healthy controls (HC). Supernatants were analyzed for cytokine levels by ELISA
      methods. mRNA expression were determined by RT-PCR. Expression and production of
      MCP-1 and IL-4 were significantly increased in AD subjects under therapy with the
      AChEI Donepezil, compared to the same AD patients at time of enrollment (P <
      0.001). Our data suggest another possible explanation for the ability of
      Donepezil [diethyl(3,5-di-ter-butyl-4-hydroxybenzyl)phosphonate] to delay the
      progression of AD; in fact, Donepezil may modulate MCP-1 and IL-4 production,
      which may reflect a general shift towards type Th0/Th2 cytokines which could be
      protective in AD disease. The different amounts of MCP-1 and IL-4 observed might
      reflect the different states of activation and/or responsiveness of PBMC, that in
      AD patients could be kept in an activated state by pro-inflammatory cytokines.

PMID- 16445951
TI  - A twin study of the effects of energy density and palatability on energy intake
      of individual foods.
AB  - The relative effects of energy density and palatability on energy intake, and
      whether there are familial influences on these effects, are not known. We
      investigated this issue in 7 pairs of healthy, male monozygotic twins (mean+/-SD
      age 26.3+/-8.6 years, BMI 23.7+/-3.2 kg/m(2)) in a clinical study involving
      covert ad libitum feeding of high-fat (HF, approximately 40%) and low-fat (LF,
      approximately 20%) diets in two 9-day phases. Diets were matched for average
      energy density, protein, fiber, and initial reported taste pleasantness, but
      these factors varied among the individual foods. Relationships between energy
      density, palatability, and energy intake were explored using regression and path
      analyses. Food energy density was positively associated with average taste
      pleasantness (r=0.46, P=0.03) independent of fat content, while energy intake
      from individual foods was positively associated with both energy density (r=0.56,
      P=0.007) and taste pleasantness (r=0.73, P<0.0001). In path analysis, both energy
      density and taste pleasantness directly influenced energy intake, and energy
      density also indirectly influenced energy intake by influencing taste
      pleasantness. In addition, there were significant within-twin pair similarities
      for the energy density-taste pleasantness and energy density-energy intake
      relationships (P<0.03) with the result that some twin pairs but not others
      identified foods high in energy density as more pleasant tasting and consumed
      relatively more energy from them compared to foods low in energy density. These
      results suggest that there are familial influences on the extent to which high
      energy density foods are preferred and contribute to total energy intake.

PMID- 16445952
TI  - Gluconic acid: an antifungal agent produced by Pseudomonas species in biological
      control of take-all.
AB  - Pseudomonas strain AN5 (Ps. str. AN5), a non-fluorescent Australian bacterial
      isolate, is an effective biological control (biocontrol) agent of the take-all
      disease of wheat caused by the fungus Gaeumannomyces graminis var. tritici (Ggt).
      Ps. str. AN5 controls Ggt by producing an antifungal compound which was purified
      by thin layer and column chromatography, and identified by NMR and mass
      spectroscopic analysis to be d-gluconic acid. Commercially bought pure gluconic
      acid strongly inhibited Ggt. Two different transposon mutants of Ps. str. AN5
      which had lost take-all biocontrol did not produce d-gluconic acid. Gluconic acid
      production was restored, along with take-all biocontrol, when one of these
      transposon mutants was complemented with the corresponding open reading frame
      from wild-type genomic DNA. Gluconic acid was detected in the rhizosphere of
      wheat roots treated with the wild-type Ps. str. AN5, but not in untreated wheat
      or wheat treated with a transposon mutant strain which had lost biocontrol. The
      antifungal compounds phenazine-1-carboxylic acid and 2,4-diacetylphloroglucinol,
      produced by other Pseudomonads and previously shown to be effective in
      suppressing the take-all disease, were not detected in Ps. str. AN5 extracts.
      These results suggest that d-gluconic acid is the most significant antifungal
      agent produced by Ps. str. AN5 in biocontrol of take-all on wheat roots.

PMID- 16445953
TI  - Membrane-bound geranylgeranyl diphosphate phosphatases: purification and
      characterization from Croton stellatopilosus leaves.
AB  - Geranylgeranyl diphosphate phosphatase is an enzyme catalyzing the
      dephosphorylation of geranylgeranyl diphosphate (GGPP) to form geranylgeraniol
      (GGOH). The enzyme activity of GGPP phosphatase was detected in leaves of Croton
      stellatopilosus, a Thai medicinal plant containing plaunotol, a commercial anti
      peptic acyclic diterpenoid. Enzymological studies of GGPP phosphatase in C.
      stellatopilosis leaves revealed that the enzyme is a membrane-bound protein that
      could be removed from 20,000g pellet by 0.1% Triton X-100 without significant
      loss of enzyme activity. The solubilized enzyme preparation was separated into
      two activity peaks, PI and PII, by BioGel A gel filtration chromatography. PI and
      PII were both partially purified and characterized. PI appeared to be a
      tetrameric enzyme with its native molecular mass of 232kDa and subunit size of
      58kDa, whereas PII was a monomeric enzyme with a molecular mass of 30-34kDa. Both
      phosphatases utilized GGPP as the preferred substrate over farnesyl and geranyl
      diphosphates. The apparent K(m) values for GGPP of PI and PII appeared to be 0.2
      and 0.1mM, respectively. Both activities were Mg(2+) independent and exhibited
      slightly acidic pH optima, 6.0-6.5 for PI and 6.5-7.0 for PII. The catalytic
      activities of PII was strongly inhibited by 1.0mM of Zn(2+), Mn(2+) and Co(2+),
      whereas that of PI was not affected. Both enzyme preparations were very stable
      upon storage at -20 degrees C for 45 days without significant loss of phosphatase
      activity. The presence of GGPP phosphatase enzymes in C. stellatopilosus is
      consistent with its putative involvement in the biosynthetic pathway of plaunotol
      although whether PI or PII is the actual enzyme involved in the pathway remains
      to be clarified.

PMID- 16445954
TI  - Discrete polymorphisms due to disruptive selection on a continuous trait--I: the
      one-locus case.
AB  - We have investigated, numerically and analytically, long-term evolution under
      frequency-dependent disruptive selection of a continuous trait varying in a
      finite range and controlled by one diploid mendelian locus. We found that
      evolution converges towards a unique long-term equilibrium where only two extreme
      phenotypes are present with frequencies identical to those of the mixed strategy
      that would be the unique ESS of the game defined by the basic fitness function of
      the model. As long as this precise phenotypic composition is preserved, any
      genetic configuration of the polymorphism is equally acceptable (selectively
      neutral) at the equilibrium. Thus the number of alleles and their dominance
      pattern may vary considerably among different equilibrium populations. If genetic
      expression of the trait is variable but the amount of variability is genetically
      modifiable, disruptive selection, acting on such modifiers, produces a steady
      increase of expression variability before the equilibrium is attained. In this
      case a population at the long-term equilibrium might even be genetically
      monomorphic, with the phenotypic dimorphism resulting from purely random
      individual variation.

PMID- 16445955
TI  - SCORPION2: a database for structure-function analysis of scorpion toxins.
AB  - Scorpion toxins are important experimental tools for characterization of vast
      array of ion channels and serve as scaffolds for drug design. General public
      database entries contain limited annotation whereby rich structure-function
      information from mutation studies is typically not available. SCORPION2 contains
      more than 800 records of native and mutant toxin sequences enriched with binding
      affinity and toxicity information, 624 three-dimensional structures and some 500
      references. SCORPION2 has a set of search and prediction tools that allow users
      to extract and perform specific queries: text searches of scorpion toxin records,
      sequence similarity search, extraction of sequences, visualization of scorpion
      toxin structures, analysis of toxic activity, and functional annotation of
      previously uncharacterized scorpion toxins. The SCORPION2 database is available
      at http://sdmc.i2r.a-star.edu.sg/scorpion/.

PMID- 16445956
TI  - Novel pathway of human immunodeficiency virus type 1 uptake and release in
      astrocytes.
AB  - Astrocytes persistently infected with HIV-1 can transmit virus to CD4+ cells,
      suggesting that astrocytes may be a source of viral persistence and dissemination
      in the brain. In the present study, we investigated the fate of HIV-1 upon
      infection of astrocytes. HIV-1 was observed in vesicle-like structures. Unspliced
      genomic RNA and extrachromosomal HIV-1 DNA were detected in astrocytes, with
      levels declining over time. The extrachromosomal viral DNA was not de novo
      reverse transcribed in astrocytes but most likely the products of intravirion
      reverse transcription present in the virus inoculum. Integrated HIV-1 DNA was not
      detected in assays sensitive to detect 2 integrated copies of provirus. However,
      the majority of astrocyte cultures released infectious virus that could be
      transmitted to CD4+ cells. Our findings suggest a novel pathway of HIV-1 uptake
      and release in astrocytes that does not necessarily require virus replication,
      which may contribute to persistence and spread of HIV-1 in the brain.

PMID- 16445958
TI  - Characterization of Maguari orthobunyavirus mutants suggests the nonstructural
      protein NSm is not essential for growth in tissue culture.
AB  - Maguari virus (MAGV; genus Orthobunyavirus, family Bunyaviridae) contains a
      tripartite negative-sense RNA genome. Like all orthobunyaviruses, the medium (M)
      genome segment encodes a precursor polyprotein (NH(2)-Gn-NSm-Gc-COOH) for the two
      virion glycoproteins Gn and Gc and a nonstructural protein NSm. The nucleotide
      sequences of the M segment of wild-type (wt) MAGV, of a temperature-sensitive
      (ts) mutant, and of two non-ts revertants, R1 and R2, that show electrophoretic
      mobility differences in their Gc proteins were determined. Twelve amino acid
      differences (2 in Gn, 10 in Gc) were observed between wt and ts MAGV, of which 9
      were maintained in R1 and R2. The M RNA segments of R1 and R2 contained internal
      deletions, resulting in the removal of the N-terminal 239 residues of Gc (R1) or
      the C-terminal two thirds of NSm and the N-terminal 431 amino acids of Gc (R2).
      The sequence data were consistent with analyses of the virion RNAs and virion
      glycoproteins. These results suggest that neither the N-terminal domain of Gc nor
      an intact NSm protein is required for the replication of MAGV in tissue culture.

PMID- 16445957
TI  - Inhibition of measles virus minireplicon-encoded reporter gene expression by V
      protein.
AB  - Measles virus V protein is a Cys-rich polypeptide that is dispensable for virus
      propagation in continuous cell lines, but necessary for efficient viral
      replication in animals. Those functions modulating virus propagation in vivo are
      not understood completely, although V protein is known to interfere with the host
      interferon response and control of viral gene expression. The ability to modulate
      gene expression was investigated further with a minireplicon transient expression
      system in which V protein was found to repress reporter activity. Two regions of
      the polypeptide contributed to this repressive effect including the carboxy
      terminus and a region conserved in morbillivirus V proteins located between amino
      acids 110-131, whereas domains known to mediate the interaction between V and the
      nucleocapsid (N) protein were not essential. Accumulation of encapsidated
      minigenome in transfected cells was inhibited by V protein suggesting that it
      acted as a repressor of genome replication thereby limiting availability of
      template for reporter gene mRNA transcription.

PMID- 16445959
TI  - Stimulus factors affecting illusory rebound motion.
AB  - Stimulus attributes that influence a recently reported illusion called "illusory
      rebound motion" (IRM; [Hsieh, P.-J., Caplovitz, G. P., & Tse, P. U. (2005).
      Illusory rebound motion and the motion continuity heuristic. Vision Research, 45,
      2972-2985.]) are described. When a bar alternates between two different colors,
      IRM can be observed to traverse the bar as if the color were shooting back and
      forth like the opening and closing of a zipper, even though each color appears in
      fact all at once. Here, we tested IRM over dynamic squares or disks defined by
      random dot or checkerboard textures to show that (1) IRM can be perceived in the
      absence of first-order motion-energy (or when the direction of net first-order
      motion-energy is ambiguous); (2) the direction of IRM is multistable and can
      change spontaneously or be changed volitionally; and (3) the perceived frequency
      of IRM is affected by several factors such as the contours of the stimulus,
      stimulus texture, and motion-energy.

PMID- 16445960
TI  - Saccadic selectivity in complex visual search displays.
AB  - Visual search is a fundamental and routine task of everyday life. Studying visual
      search promises to shed light on the basic attentional mechanisms that facilitate
      visual processing. To investigate visual attention during search processes,
      numerous studies measured the selectivity of observers' saccadic eye movements
      for local display features. These experiments almost entirely relied on simple,
      artificial displays with discrete search items and features. The present study
      employed complex search displays and targets to examine task-driven (top-down)
      visual guidance by low-level features under more natural conditions. Significant
      guidance by local intensity, contrast, spatial frequency, and orientation was
      found, and its properties such as magnitude and resolution were analyzed across
      dimensions. Moreover, feature-ratio effects were detected, which correspond to
      distractor-ratio effects in simple search displays. These results point out the
      limitations of current purely stimulus-driven (bottom-up) models of attention
      during scene perception.

PMID- 16445961
TI  - Proprioceptive role for palisade endings in extraocular muscles: evidence from
      the Jendrassik Maneuver.
AB  - A proprioceptive hypothesis for the control of eye movements has been recently
      proposed based on neuroanatomical tracing studies. It has been suggested that the
      non-twitch motoneurons could be involved in modulating the gain of sensory
      feedback from the eye muscles analogous to the gamma (gamma) motoneurons which
      control the gain of proprioceptive feedback in skeletal muscles. We conducted
      behavioral and psychophysical experiments to test the above hypothesis using the
      Jendrassik Maneuver (JM) to alter the activity of gamma motoneurons. It was
      hypothesized that the JM would alter the proprioceptive feedback from the eye
      muscles which would result in misregistration of eye position and mislocalization
      of targets. In the first experiment, vergence eye movements and pointing
      responses were examined. Data showed that the JM affected the localization
      responses but not the actual eye position. Perceptual judgments were tested in
      the second experiment, and the results showed that targets were perceived as
      farther when the afferent feedback was altered by the JM. Overall, the results
      from the two experiments showed that eye position was perceived as more divergent
      with the JM, but the actual eye movements were not affected. We tested this
      further in Experiment 3 by examining the effect of JM on the amplitude and
      velocity of saccadic eye movements. As expected, there were no significant
      differences in saccadic parameters between the control and experimental
      conditions. Overall, the present study provides novel insight into the mechanism
      which may be involved in the use of sensory feedback from the eye muscles. Data
      from the first two experiments support the hypothesis that the JM alters the
      registered eye position, as evidenced by the localization errors. We propose that
      the altered eye position signal is due to the effect of the JM which changes the
      gain of the sensory feedback from the eye muscles, possibly via the activity of
      non-twitch motoneurons.

PMID- 16445962
TI  - Recent progress in understanding of the levels, trends, fate and effects of BFRs
      in the environment.

PMID- 16445963
TI  - Role of plant activity and contaminant speciation in aquatic plant assimilation
      of 2,4,5-trichlorophenol.
AB  - Aquatic plants uptake, transform and sequester organic contaminants and are used
      as a bioremediation strategy for the removal of pollutants from wastewaters. A
      better understanding of factors affecting rate of uptake of contaminants by
      aquatic plants is needed to improve engineered systems for removal of pollutants
      from wastewaters. This work focused on delineating sorption to plant surfaces and
      understanding effects of plant metabolic activity, inhibition, and media pH on
      the uptake of the ionizable contaminant 2,4,5-trichlorophenol (TCP) by aquatic
      plant Lemna minor. During L. minor exposure to TCP (0.5-13.9 mg l(-1)), a range
      of plant metabolic activities was measured using oxygen production rate (0-18.4
      micromol h(-1)). A positive correlation was shown between contaminant uptake rate
      and plant activity. Contaminant uptake was examined at a range of media pH values
      (6-9) and uptake rates were linearly correlated to fraction of contaminant in
      protonated form. These results demonstrated a link between plant activity and
      uptake of contaminant by plants and stress the importance of incorporating plant
      metabolic activity and contaminant speciation in development of natural and
      engineered phytoremediation systems. This research also indicates that aquatic
      plants can actively accumulate trace-organic contaminants and may ultimately
      serve as a sink for these materials in the natural environment.

PMID- 16445964
TI  - Polybrominated diphenyl ethers (PBDEs) in mussels from selected French coastal
      sites: 1981-2003.
AB  - The present study focused on the retrospective analysis of PBDEs in archived blue
      mussel (Mytilus edulis or Mytilus galloprovincialis) samples collected over the
      past 22 years (1981-2003) from coastal areas of France. We have found that PBDE
      levels in mussels from the English Channel increased markedly from 1981 to 1991
      1995, doubling approximately every 5-6 years followed by a levelling off and a
      possible beginning of a decrease. The rate of the decline of hexa- and hepta-BDE
      congeners was more rapid than the decline of tetra- and penta-BDEs in these
      mussel samples. The difference in the course of time of lower and higher
      brominated PBDE concentrations suggests that the congener profile in the mussel
      samples changes over time. The increase in PBDE concentrations in the mussel
      samples contrasts with a concomitant constant decrease of chlorobiphenyls (CBs)
      in the same set of samples. However, pulse inputs of both groups of organohalogen
      compounds were determined for the mussel samples collected at the mouth of the
      Seine estuary and were probably related to riverine inundations and a flushing
      out of the deposited sediments from the internal estuary into the bay of the
      River Seine, as well as considerable dredging activities taking place during same
      years. In France, the highest PBDE concentrations were determined in the mussels
      from the English Channel, more precisely in the bay of the Seine, and the
      regional differences in PBDE levels were mainly connected to the difference in
      anthropogenic urban and industrial environmental pressures. Published data
      comparing PBDE levels in mussels have shown significant differences in
      concentrations between North/South America and Europe. This observation further
      confirms that the PBDE levels in the North American environment are higher than
      in Europe. However, the data used for this comparison of mussel contamination by
      PBDEs is still relatively sparse.

PMID- 16445965
TI  - Enzymatic degradation of anthracene, dibenzothiophene and pyrene by manganese
      peroxidase in media containing acetone.
AB  - The high hydrophobicity of polycyclic aromatic hydrocarbons (PAHs) greatly hamper
      their degradation in liquid media. The use of an organic solvent can assist the
      degradative action of ligninolytic enzymes from white rot fungi. The enzymatic
      action of the enzyme manganese peroxidase (MnP) in media containing a miscible
      organic solvent, acetone (36% v/v), was evaluated as a feasible system for the in
      vitro degradation of three PAHs: anthracene, dibenzothiophene and pyrene. These
      compounds were degraded to a large extent after a short period of time (7, 24 and
      24h, respectively), at conditions maximizing the MnP-oxidative system. The
      initial amount of enzyme present in the reaction medium was determinant for the
      kinetics of the process. The order of degradability, in terms of degradation
      rates was as follows: anthracene>dibenzothiophene>pyrene. The intermediate
      compounds were determined using gas chromatography-mass spectrometry and the
      degradation mechanisms were proposed. Anthracene was degraded to phthalic acid. A
      ring cleavage product of the oxidation of dibenzothiophene, 4-methoxybenzoic
      acid, was also observed.

PMID- 16445966
TI  - Kinematics of vertical climbing in lorises and Cheirogaleus medius.
AB  - The type of climbing exhibited by apes and atelines is argued to have been
      important in the evolution of specialized locomotion, such as suspensory
      locomotion and bipedalism. However, little is known about the mechanics of
      climbing in primates. Previous work shows that Asian apes and atelines use larger
      joint excursions and longer strides than African apes and the Japanese macaque,
      respectively. This study expands knowledge of climbing mechanics by providing the
      first quantitative kinematic data for vertical climbing in four prosimian
      species: three lorisid species (Loris tardigradus, Nycticebus coucang, and
      Nycticebus pygmaeus) that share with apes and atelines morphological traits
      arguably related to climbing, and a more generalized quadruped, Cheirogaleus
      medius. Subjects were videotaped as they climbed up a wooden pole. Kinematic
      values, such as step length and limb excursions, were calculated and compared
      between species. The results of this study show that lorises, like Asian apes and
      spider monkeys, use relatively larger joint excursions and longer steps than does
      C. medius during climbing. These data lend further support to the idea that some
      primate species (e.g., lorises, atelines, and apes) are more specialized
      kinematically and morphologically for climbing than others. Pilot data suggest
      that such kinematic differences in climbing style across broad phylogenetic
      groups may relate to the energetics of climbing. Such data may be important for
      understanding the morphological and kinematic adaptations to climbing exhibited
      by some primates.

PMID- 16445967
TI  - Age-related changes in lamin A/C expression in the osteoarticular system:
      laminopathies as a potential new aging mechanism.
AB  - BACKGROUND: Mutations in lamin A/C have been described as associated to severe
      changes in bone and joints. In this study we hypothesize that the expression of
      lamin A/C may play a role in the pathogenesis of age-related diseases in the
      osteoarticular system. METHODOLOGY: C57BL/6 young and old mice (4 months; n=10
      and 24 months; n=10) were sacrificed. Limbs were isolated for histopathological
      and Western blot analysis. The proportion of cells (osteoblasts and chondrocytes)
      positive for lamin A/C was quantified by immunohistochemistry. Lamin B1 was used
      as control. Finally, lamin A/C expression in bone marrow cells was quantified by
      Western blot. RESULTS: A significant reduction in lamin A/C was found in
      osteoblasts of old as compared to young mice (42% versus 76%, p<0.001).
      Interestingly, lamin A/C but not lamin B1 expression was found in bone matrix
      with higher levels in young bone. Additionally, a significant reduction in the
      number of lamin A/C expressing chondrocytes was seen in old mice as compared to
      young mice (32% versus 84%, p<0.001). Finally, a reduction in lamin A/C
      expression was found in bone marrow cells obtained from old mice as compared to
      young mice. CONCLUSION: This is the first assessment of the age-related changes
      in lamin A/C expression in the osteoarticular system. We conclude that with aging
      there is a reduction in lamin A/C expression which could have a significance on
      osteoarticular cells function and viability.

PMID- 16445968
TI  - Type II versus Type III nerve-sparing radical hysterectomy: comparison of lower
      urinary tract dysfunctions.
AB  - OBJECTIVES: According to our previous experience, Type III Nerve-sparing Radical
      hysterectomy (NSRH) for cervical cancer presented an acceptable urologic
      morbidity, without compromising radicality. The aim of this study was to compare
      Type NSRH with other types of RH in terms of incidence of early bladder
      dysfunctions and perioperative complications. METHODS: One hundred and ten
      patients with cervical cancer were submitted to Type II RH (group 1), Type III
      NSRH (group 2) and Type III RH (group 3). We assessed the postoperative early
      bladder function and complications. The follow-up period was 3 months. RESULTS:
      Group 1 had a significantly shorter duration of the surgery, minor mean blood
      loss and shorter mean length of postoperative stay when compared to groups 2 and
      3. No intraoperative complications were reported in either of the groups. The
      groups did not differ significantly in terms of GIII/IV morbidity (group 1 = 10%,
      group 2 = 10% and group 3 = 15%, chi(2), P value: 0.65). Not even they differed
      in terms of urologic GI-IV morbidity (group 1 = 13%, group 2 = 15% and group 3 =
      10%, chi(2), P value = 0.88). Groups 1 and 2 presented a prompt recover of
      bladder function, significantly different from that of group 3. There was a
      significant difference between the groups regarding the number of patients
      discharged with self-catheterism (group 1 = 0; group 2 and group 3 = 11; chi(2),
      P value << 0.05). CONCLUSIONS: The Type III NSRH seems to be comparable to Type
      II RH and superior to Type III RH in terms of early bladder dysfunctions.

PMID- 16445969
TI  - A study to evaluate the use of CA125 in ovarian cancer follow-up: A change in
      practice led by patient preference.
AB  - OBJECTIVES: To evaluate the use of CA125 in the follow-up of women with
      epithelial ovarian cancer in the Cambridge Gynaecologic Oncology Centre. To
      institute changes depending on patients' preferences. METHODS: A patient
      questionnaire was developed on follow-up, CA125 estimation and patient education
      in epithelial ovarian cancer and CA125. Initially, 100 patients were evaluated,
      and a change in practice was instituted. This was re-evaluated using the same
      patient population. RESULTS: 22/22 patients in clinic, and 68/78 patients who
      received the questionnaire by post, completed and returned it (n = 90). 81%
      wanted CA125 results available at clinic follow-up visits, with 82% willing to
      have the blood test done at their GP surgery before attending outpatients. CA125
      follow-up practice was changed accordingly. This change was re-evaluated. A
      second questionnaire was sent to 35 surviving patients from the first cohort.
      31/35 (90%) responses were received. Five patients were either no longer on
      follow-up, being > or =5 years from completing their original treatment or were
      being monitored elsewhere, leaving an 87% response rate (26/30). 92.3% felt that
      having CA125 results available in clinic had enhanced the quality of their follow
      up. Patient education and basic understanding of CA125 also improved, with 88.5%
      aware of its role. CONCLUSIONS: The availability of CA125 results when patients
      attend for routine follow-up has improved their overall management in our
      clinics. It has reduced patient and physician anxiety and unsatisfactory out-of
      clinic telephone communication. We recommend this change of practice to all
      Gynaecologic Oncology Centres engaged in active routine follow-up of their
      patients with epithelial ovarian cancer.

PMID- 16445971
TI  - Religious attendance and the health behaviors of Texas adults.
AB  - OBJECTIVE: The purpose of this study is to test whether religious involvement is
      associated with a broad range of health behaviors. METHOD: We employ data from
      the 2004 Survey of Texas Adults, a statewide probability sample of 1504 Texas
      adults. Using these data, we estimate a series of logistic regression models to
      assess the net effects of religious attendance on 12 health behaviors. RESULTS:
      Our results show that regular religious attendance (especially weekly attendance)
      is associated with a wide range of healthy behaviors, including preventive care
      use, vitamin use, infrequent bar attendance, seatbelt use, walking, strenuous
      exercise, sound sleep quality, never smoking, and moderate drinking. CONCLUSION:
      If religious involvement is associated with healthy behaviors, additional studies
      are needed to account for these associations. Future research might also consider
      health behaviors other than drinking and smoking as potential mechanisms through
      which religious involvement might benefit health and prolong life.

PMID- 16445970
TI  - Memantine increases cardiovascular but not behavioral effects of cocaine in
      methadone-maintained humans.
AB  - Previous work has suggested that maintenance on the noncompetitive N-methyl-d
      aspartate (NMDA) antagonist, memantine, increased the subjective effects of
      smoked cocaine in experienced cocaine users. To determine whether this phenomenon
      occurs in opioid-dependent individuals, eight (seven male, one female) methadone
      maintained cocaine smokers participated in a 47-day inpatient and outpatient
      study to assess the effects of memantine on smoked cocaine self-administration,
      subjective effects, and cardiovascular responses. The participants were
      maintained on memantine (0 mg and 20 mg daily) for 7-10 days prior to laboratory
      testing, using a double-blind crossover design. Under each medication condition
      during inpatient phases, participants smoked a sample dose of cocaine base (0,
      12, 25, and 50 mg) once, and were subsequently given five choice opportunities,
      14 min apart, to self-administer that dose of cocaine or receive a merchandise
      voucher (US 5.00 dollars). Each cocaine dose was tested twice under each
      medication condition, and the order of medication condition and cocaine dose were
      varied systematically. Memantine maintenance did not alter the subjective or
      reinforcing effects of cocaine. Several cardiovascular responses, however,
      including peak and initial diastolic pressures following cocaine, were
      significantly greater during memantine maintenance, although these elevations
      were not clinically significant. Taken together, these findings corroborate
      earlier data suggesting that this dose of memantine will not be helpful in the
      pharmacotherapy of cocaine abuse.

PMID- 16445972
TI  - The relationship of neuronal activity within the sensori-motor region of the
      subthalamic nucleus to speech.
AB  - Microelectrode recordings of human sensori-motor subthalamic neuronal activity
      during spoken sentence and syllable-repetition tasks provided an opportunity to
      evaluate the relationship between changes in neuronal activities and specific
      aspects of these vocal behaviors. Observed patterns of neuronal activity included
      a build up of activity in anticipation of the start of the utterance, a marked
      reduction in activity associated with the start of the utterance, and a burst of
      activity during the course of the sentence between the noun phrase and the verb
      phrase. Overall, changes of neuronal activity were more robust for the sentence
      repetition task. These data suggest that the basal ganglia play a role in
      generating meaningful speech utterances, which may parallel its role in complex
      sequential limb movements. It is possible that the basal ganglia play a role in
      generating the syntactical structure of language.

PMID- 16445973
TI  - The transition to increased automaticity during finger sequence learning in adult
      males who stutter.
AB  - The present study compared the automaticity levels of persons who stutter (PWS)
      and persons who do not stutter (PNS) on a practiced finger sequencing task under
      dual task conditions. Automaticity was defined as the amount of attention
      required for task performance. Twelve PWS and 12 control subjects practiced
      finger tapping sequences under single and then dual task conditions. Control
      subjects performed the sequencing task significantly faster and less variably
      under single versus dual task conditions while PWS' performance was consistently
      slow and variable (comparable to the dual task performance of control subjects)
      under both conditions. Control subjects were significantly more accurate on a
      colour recognition distracter task than PWS under dual task conditions. These
      results suggested that control subjects transitioned to quick, accurate and
      increasingly automatic performance on the sequencing task after practice, while
      PWS did not. Because most stuttering treatment programs for adults include
      practice and automatization of new motor speech skills, findings of this finger
      sequencing study and future studies of speech sequence learning may have
      important implications for how to maximize stuttering treatment effectiveness.
      EDUCATIONAL OBJECTIVES: As a result of this activity, the participant will be
      able to: (1) Define automaticity and explain the importance of dual task
      paradigms to investigate automaticity; (2) Relate the proposed relationship
      between motor learning and automaticity as stated by the authors; (3) Summarize
      the reviewed literature concerning the performance of PWS on dual tasks; and (4)
      Explain why the ability to transition to automaticity during motor learning may
      have important clinical implications for stuttering treatment effectiveness.

PMID- 16445974
TI  - Real-time reverse transcription PCR and the detection of occult disease in
      colorectal cancer.
AB  - Molecular diagnostics offers the promise of accurately matching patient with
      treatment, and a resultant significant effect on improved disease outcome. More
      specifically, the real-time reverse transcription polymerase chain reaction (qRT
      PCR), with its combination of conceptual simplicity and technical utility, has
      the potential to become a valuable analytical tool for the detection of mRNA
      targets from tissue biopsies and body fluids. Its potential is particularly
      promising in cancer patients, both as a prognostic assay and for monitoring
      response to therapy. Colorectal cancer provides an instructive paradigm for this
      potential as well as the problems associated with its use as a clinical assay.
      Currently, histopathological staging, which provides a static description of the
      anatomical extent of tumour spread within a surgical specimen, defines patient
      prognosis. The detection of lymph node (LN) metastasis constitutes the most
      important prognostic factor in colorectal cancer and as the primary indicator of
      systemic disease spread, LN status determines the choice of postoperative
      adjuvant chemotherapy. However, its limitations are emphasised by the
      considerable prognostic heterogeneity of patients within a given tumour stage:
      not all patients with LN-negative cancers are cured and not all patients with LN
      positive tumours die from their disease. This has resulted in a search for more
      accurate staging protocols and has seen the introduction of the concept of
      "molecular staging", the incorporation of molecular parameters into clinical
      tumour staging. Quantification of disease-associated mRNA is one such parameter
      that utilises the qRT-PCR assay's potential for generating quantitative results.
      These are not only more informative than qualitative data, but contribute to
      assay standardisation and quality management. This review provides an assessment
      of the practical value to the clinician of RT-PCR-based molecular diagnostics. It
      points out reasons for the many contradictory results encountered in the
      literature and concludes that there is an urgent need for standardisation at
      every level, starting with pre-assay sample acquisition and template preparation,
      assay protocols and post-assay analysis.

PMID- 16445975
TI  - Over-expression of p53/BAK in aseptic loosening after total hip replacement.
AB  - Particle-induced osteolysis is a major cause of aseptic loosening after total
      joint replacement. The possible induction of apoptosis has not been addressed in
      great detail. Thus far, it has been shown that ceramic and polyethylene particles
      can induce apoptosis of macrophages in vitro. The purpose of this study was to
      test the hypothesis that wears debris generated from total hip arthroplasty could
      induce cellular damage and apoptosis in vivo. We therefore determined by
      immunohistochemical methods if increased expression of p53, an important
      transcription factor, and BAK and Bcl-2, two important regulators of apoptosis,
      can be found in interface membranes and capsules of hips with aseptically loose
      implants. Strongly positive immunohistochemical staining for p53 and BAK was
      found in peri-implant tissues from patients with aseptic hip implant loosening.
      Differentiation of various cell types showed that macrophages stained positive
      for p53 in all capsule and interface specimens. p53 was frequently detected in
      giant cells. Positive staining of BAK in macrophages and giant cells was seen in
      all specimens. Some positive reactions were observed in fibroblasts, only two of
      19 cases stained for p53 and three cases for BAK within synovial cells. Positive
      macrophages and giant cells were localized around polyethylene particles. While T
      lymphocytes showed a regular BAK-staining, the other leukocytes were negative.
      Statistical analyses showed significant positive correlations (p < 0.001) between
      the presence of polyethylene and metal debris and the expression of BAK and p53.
      Polyethylene particles were surrounded by more positive macrophages and giant
      cells than were metal particles, indicating that polyethylene debris may be a
      stronger inductor of cell cycle arrest and apoptosis than metal debris. In this
      study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and
      interface membranes of patients with aseptic hip implant loosening has been
      demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a
      novel therapeutic target to prevent particle-induced osteolysis.

PMID- 16445976
TI  - Peptide-surface modification of poly(caprolactone) with laminin-derived sequences
      for adipose-derived stem cell applications.
AB  - Human adipose tissue has been recognized as a source of adult stem cells for
      tissue engineering applications such as bone, cartilage, and soft tissue repair.
      For the success of these tissue-engineering approaches, a cell delivery vehicle
      such as a hydrogel or scaffold is required to position the stem cells at the site
      of need. Surface modification techniques have been instrumental in the
      development of scaffolds that promote cell-surface interactions. In this study,
      poly(caprolactone) (PCL), surfaces were modified in order to promote the
      attachment and proliferation of adipose-derived stem cells (ASCs). RGD, YIGSR,
      and IKVAV peptide sequences derived from the extracellular matrix protein laminin
      were each covalently attached to an aminated polymer surface using carbodiimide
      chemistry. The surface was characterized using scanning electron microscopy
      (SEM), goniometry and X-ray photoelectron spectroscopy (XPS). The attachment and
      proliferation of ASCs was assessed on the different peptide-treated surfaces. XPS
      analysis confirmed the presence of the peptide sequences on the surface of the
      polymer as indicated by the increase in the nitrogen/carbon ratio on the surface
      of the polymer. Among all peptide sequences tested, IKVAV-treated surfaces had a
      significantly greater number of ASCs bound 2 and 3 days after cell seeding. SEM
      confirmed differences in the morphology of the cells attached to the three
      peptide-treated surfaces. These results indicate that IKVAV is a suitable peptide
      sequence for use in surface modification techniques aimed at improving the
      attachment of ASCs to a tissue-engineered scaffold.

PMID- 16445977
TI  - ATP autocrine/paracrine signaling induces calcium oscillations and NFAT
      activation in human mesenchymal stem cells.
AB  - Human bone marrow-derived mesenchymal stem cells (hMSCs) have the potential to
      differentiate into several types of cells. Calcium ions (Ca(2+)) play an
      important role in the differentiation and proliferation of hMSCs. We have
      demonstrated that spontaneous [Ca(2+)](i) oscillations occur without agonist
      stimulation in hMSCs. However, the precise mechanism of its generation remains
      unclear. In this study, we investigated the mechanism and role of spontaneous
      [Ca(2+)](i) oscillations in hMSCs and found that IP(3)-induced Ca(2+) release is
      essential for spontaneous [Ca(2+)](i) oscillations. We also found that an ATP
      autocrine/paracrine signaling pathway is involved in the oscillations. In this
      pathway, an ATP is secreted via a hemi-gap-junction channel; it stimulates the
      P(2)Y(1) receptors, resulting in the activation of PLC-beta to produce IP(3). We
      were able to pharmacologically block this pathway, and thereby to completely halt
      the [Ca(2+)](i) oscillations. Furthermore, we found that [Ca(2+)](i) oscillations
      were associated with NFAT translocation into the nucleus in undifferentiated
      hMSCs. Once the ATP autocrine/paracrine signaling pathway was blocked, it was not
      possible to detect the nuclear translocation of NFAT, indicating that the
      activation of NFAT is closely linked to [Ca(2+)](i) oscillations. As the hMSCs
      differentiated to adipocytes, the [Ca(2+)](i) oscillations disappeared and the
      translocation of NFAT ceased. These results provide new insight into the
      molecular and physiological mechanism of [Ca(2+)](i) oscillations in
      undifferentiated hMSCs.

PMID- 16445978
TI  - Mathematical modeling of calcium homeostasis in yeast cells.
AB  - In this study, based on currently available experimental observations on protein
      level, we constructed a mathematical model to describe calcium homeostasis in
      normally growing yeast cells (Saccharomyces cerevisiae). Simulation results show
      that tightly controlled low cytosolic calcium ion level can be a natural result
      under the general mechanism of gene expression feedback control. The calmodulin
      (a sensor protein) behavior in our model cell agrees well with relevant
      observations in real cells. Moreover, our model can qualitatively reproduce the
      experimentally observed response curve of real yeast cell responding to step-like
      disturbance in extracellular calcium ion concentration. Further investigations
      show that the feedback control mechanism in our model is as robust as it is in
      real cells.

PMID- 16445980
TI  - Sequence and analysis of the 46.6-kb plasmid pA1 from Sphingomonas sp. A1 that
      corresponds to the typical IncP-1beta plasmid backbone without any accessory
      gene.
AB  - Sphingomonas sp. A1 (strain A1) is capable of directly incorporating
      macromolecules (e.g., alginate) through the specialized import system--"super
      channel." Here, we report the complete DNA sequence and genetic organization of
      plasmid pA1 from strain A1. Nucleotide sequence analysis revealed that pA1
      comprises 46,557 bp encoding 49 open reading frames (ORFs) with 65% G+C content
      and abundant GCCG/CGGC motifs. Many predicted pA1 ORFs showed high similarity to
      pA81 ORFs; pA81 is supposedly a self-transmissible promiscuous incompatibility
      (Inc) group P-1beta plasmid. Unlike any reported IncP-1 plasmids, pA1 contains no
      inserted mobile genetic elements. The genetic organization and predicted pA1 ORFs
      showed greater similarity to the IncP-1beta plasmid backbone than to the IncP
      1alpha plasmid backbone. pA1 contains restriction site-associated repeat
      sequences typical of the IncP-1beta but absent in the IncP-1alpha and delta
      subgroups. Thus, the overall pA1 structure corresponds to that of the typical
      IncP-1beta plasmids. Phylogenetic analysis of the replication-associated proteins
      suggested that pA1 may have diverged later along with the two IncP-1beta plasmids
      -pA81 and pB4. The 2.4-kb duplicates of stable inheritance genes klcAB and korC
      in pA1 possibly resulted from insertion and/or recombination events via the
      repeat sequences flanking these duplicates.

PMID- 16445979
TI  - Successful treatment of primary refractory anemia with a combination regimen of
      all-trans retinoic acid, calcitriol, and androgen.
AB  - We investigated the efficacy and safety of a combination regimen in 63 patients
      with primary refractory anemia (RA). The daily treatment protocol comprised all
      trans retinoic acid (ATRA) (30 mg/m(2)), calcitriol (0.1 microg/m(2)), and
      androgen (stanozolol 3mg/m(2), or danazol 300 mg/m(2)) in three separate doses
      for eight consecutive weeks. Hematologic improvement was observed in 43 (68.3%)
      patients. The treatment administered was generally well tolerated, with no severe
      regimen-related toxicity. The overall survival rates at 3 and 5 years were 68.72%
      and 53.18%, respectively. These results indicate that this combination regimen is
      an effective and well-tolerated treatment for patients with RA.

PMID- 16445981
TI  - RNA metabolism and dysmyelination in schizophrenia.
AB  - Decreased expression of a subset of oligodendrocyte and myelin-related genes is
      the most consistent finding among gene expression studies of postmortem brain
      tissue from subjects with schizophrenia (SCZ), although heritable variants have
      yet to be found that can explain the bulk of this data. However, expression of
      the glial gene Quaking (QKI), encoding an RNA binding (RBP) essential for
      myelination, was recently found to be decreased in SCZ brain. Both
      oligodendrocyte/myelin related genes, and other RBPs that are known or predicted
      to be targets of QKI, are also decreased in SCZ. Two different quaking mutant
      mice share some pathological features in common with SCZ, including decreased
      expression of myelin-related genes and dysmyelination, without gross destruction
      of white matter. Therefore, although these mice are not a model of SCZ per se,
      understanding the similarities and differences in gene expression between brains
      from these mice and subjects with SCZ could help parse out distinct genetic
      pathways underlying SCZ.

PMID- 16445982
TI  - Organochlorine compounds and stable isotopes indicate bottlenose dolphin
      subpopulation structure around the Iberian Peninsula.
AB  - Isotopic signatures and organochlorine pollutant loads of organisms reflect the
      characteristics of the waters in which they live and feed. To investigate
      population structure of bottlenose dolphins around the Iberian Peninsula we
      determined delta(13)C and delta(15)N in the skin and organochlorine (OC) levels
      in the blubber of stranded bottlenose dolphins inhabiting the Mediterranean
      (Catalonia, Valencia and Balearic Islands) and adjacent Atlantic waters (Huelva
      and Portugal). OC levels were high in all regions, reflecting the predatory
      habits of the species, its coastal distribution and the existence of intense
      agricultural and industrial activity throughout the region. PCB congeners showed
      a gradient from the relatively more chlorinated forms to those that are less so,
      and followed a northeast to northwest direction across the Iberian Peninsula.
      This suggests that PCB inputs are more recent in the temperate latitudes of the
      eastern Atlantic Ocean than in the western Mediterranean Sea. Comparatively, OC
      ratios and isotopic signatures proved to be more efficient ways of discriminating
      groups than did raw OC concentrations. Significant differences in delta(13)C and
      in PCB congener profiles indicate that dolphins from the Atlantic and the
      Mediterranean do not intermingle. In addition, the two Atlantic groups differed
      in delta(15)N signature, tDDT concentration, DDT/PCB ratio and the PCB congener
      profile, which also suggests some degree of isolation between them. In the
      Mediterranean, dolphins from Catalonia and Valencia were indistinguishable,
      suggesting a common distribution area. However, dolphins from the Balearic
      Islands differed from those of the Peninsula in their DDT/PCB ratio and from all
      the other sample groups in their PCB congener profiles, which supports the
      hypothesis that the deep waters between the Islands and the Peninsula represent
      an effective barrier for the species.

PMID- 16445984
TI  - Comparison of etiology and resistance in respiratory isolates of AIDS patients
      vs. non-AIDS patients in South Sudan and Kenya.

PMID- 16445985
TI  - Noninvasive imaging of atherosclerotic vessels by MRI for clinical assessment of
      the effectiveness of therapy.
AB  - Atherosclerosis and its thrombotic complications are the major cause of morbidity
      and mortality in the industrialized countries. Despite advances in our
      understanding of the mechanisms of pathogenesis and new treatment modalities, the
      absence of an adequate noninvasive method for early detection limits prevention
      or treatment of patients with various degrees and localizations of
      atherothrombotic disease. The ideal clinical imaging modality for atherosclerosis
      should be safe, inexpensive, noninvasive or minimally invasive, accurate, and
      reproducible, thus allowing longitudinal studies in the same patients.
      Additionally, the results should correlate with the extent of atherosclerotic
      disease and have high predictive values for clinical events. In vivo, high
      resolution magnetic resonance imaging (MRI) has recently emerged as one of the
      most promising techniques for the noninvasive study of atherothrombotic disease
      in several vascular beds such as the aorta, the carotid arteries, and the
      coronary arteries. Most importantly MRI can be used to characterize plaque
      composition as it allows the discrimination of lipid core, fibrosis,
      calcification, and intra-plaque hemorrhage deposits. MRI findings have been
      extensively validated against pathology in ex vivo studies of carotid, aortic,
      and coronary artery specimens obtained at autopsy and using experimental models
      of atherosclerosis. In vivo MRI of carotid arteries of patients referred for
      endarterectomy has shown a high correlation with pathology and with previous ex
      vivo results. A recent study in patients with plaques in the thoracic aorta
      showed that compared with transesophageal echocardiography plaque composition and
      size are more accurately characterized and measured using in vivo MRI. The
      composition of the plaque rather than the degree of stenosis determines the
      patient outcome. Therefore, a reliable noninvasive imaging tool able to detect
      early atherosclerotic disease in the various regions and identify the plaque
      composition is clinically desirable. MRI has potential in the detection arterial
      thrombi and in the definition of thrombus age. MRI has been used to monitor
      plaque progression and regression in several animal model of atherosclerosis and
      more recently in human. Advances in diagnosis prosper when they march hand-in
      hand with advances in treatment. We stand at the threshold of accurate
      noninvasive assessment of atherosclerosis. Thus, MRI opens new strategies ranging
      from screening of high-risk patients for early detection and treatment as well as
      monitoring the target areas for pharmacological intervention.

PMID- 16445986
TI  - Ceramides in insulin resistance and lipotoxicity.
AB  - Obesity predisposes individuals to the development of insulin resistance in
      skeletal muscle and the liver, and researchers have recently proposed two
      mechanisms by which excess adiposity antagonizes insulin action in peripheral
      tissues. First, when adipocytes exceed their storage capacity, fat begins to
      accumulate in tissues not suited for lipid storage, leading to the formation of
      specific metabolites that inhibit insulin signal transduction. Second, obesity
      triggers a chronic inflammatory state, and cytokines released from either
      adipocytes or from macrophages infiltrating adipose tissue antagonize insulin
      action. The sphingolipid ceramide is a putative intermediate linking both excess
      nutrients (i.e. saturated fatty acids) and inflammatory cytokines (e.g. tumor
      necrosis factor-alpha, TNFalpha) to the induction of insulin resistance.
      Moreover, ceramide has been shown to be toxic in a variety of different cell
      types (e.g. pancreatic beta-cells, cardiomyocytes, etc.), and review of the
      literature reveals putative roles for the sphingolipid in the damage of cells and
      tissues which accompany diabetes, hypertension, cardiac failure, atherosclerosis,
      etc. In this review, I will evaluate the contribution of ceramides in the
      development of insulin resistance and the complications associated with metabolic
      diseases.

PMID- 16445987
TI  - A device for the electrophysiological recording of peripheral nerves in response
      to stretch.
AB  - The functional consequences of nervous tissue subjected to mechanical loads are
      of vital importance in successful clinical outcomes and in tissue engineered
      applications. In this paper, we developed a new ex vivo device that permitted the
      recording of nerve action potentials while the nerve was subjected to elongation.
      Experimental results showed guinea pig nerves to possess an inherent tolerance to
      mild stretch. The mean elongation at which the compound action potential (CAP)
      amplitude began to decrease was found to be 8.3 +/- 0.56%. The CAP response to
      stretch was immediate beyond this threshold. After 17.5 +/- 0.74% elongation, the
      CAP levels decreased to approximately 50% of its uninjured values. When allowed
      to relax, the CAP recovered almost completely within minutes. Based on the
      temporal scale of the CAP response and the presence of oxygen during testing, we
      conclude that the initial mechanism to CAP degradation cannot be ischemia. Since
      it is inherently difficult to study mechanical damage independent of hemodynamic
      factors in vivo, the developed model could be used to further elucidate the
      injury mechanisms of stretch-induced trauma. The design of the ex vivo chamber
      will also permit the administration and assessment of pharmacological agents on
      electrical conduction in various deformation conditions.

PMID- 16445988
TI  - Towards a proper estimation of phase synchronization from time series.
AB  - In experimental synchronization studies a continuous phase variable is commonly
      estimated from a scalar time series by means of its representation on the complex
      plane. The aim is to obtain a pair of functions [A(t), phi(t)] defining its
      instantaneous amplitude and phase, respectively. However, any arbitrary pair of
      functions cannot be considered as the amplitude and the phase of the real
      observable. Here, we point out some criteria that the pair [A(t), phi(t)] must
      observe to unambiguously define the instantaneous amplitude and phase of the
      observed signal. In this work, we illustrate how the complex representation may
      fail if the signal possesses a multi-component or a broadband spectra. We also
      point out a practical procedure to test whether a signal, not displaying a single
      oscillation at a unique frequency, has a narrow-band behavior. Implications for
      the study of phase interdependencies are illustrated and discussed. Phase
      dynamics estimated from electric brain activities recorded from an epileptic
      patient are also discussed.

PMID- 16445989
TI  - Association of psychosis with suicidality in pediatric bipolar I, II and bipolar
      NOS patients.
AB  - BACKGROUND: Psychosis in pediatric mood disorder patients may be related to
      suicidal ideation. Bipolar (BP) adolescents are at high risk of completed
      suicide. We examined whether pediatric BP patients with psychosis have a higher
      prevalence of suicidality than non-psychotic BP patients. Based on previous
      findings in adult BP patients, we predicted that pediatric BP patients with
      psychotic symptoms would have higher prevalence of suicidality, higher occurrence
      of lifetime psychiatric hospitalizations and worse current Global Assessment of
      Functioning Scale (GAF) scores compared to non-psychotic BP patients. METHODS: We
      studied 43 BP children and adolescents (mean age +/- S.D = 11.2 +/- 2.8 y, range
      = 8-17) who did (n = 17) or did not have (n = 26) a lifetime history of psychotic
      symptoms. Indicators of suicidality (thoughts of death and suicidal ideation,
      plans, and attempts), psychiatric diagnoses, psychotic symptoms, psychiatric
      hospitalizations and GAF scores were assessed with the K-SADS-PL interview.
      LIMITATIONS: Small sample size, cross-sectional study and exclusion of substance
      abuse comorbidity. RESULTS: Pediatric BP patients with a lifetime history of
      psychotic symptoms compared to BP patients without psychosis were more likely to
      have thoughts of death (100% versus 69.2%, p = 0.01), suicidal ideation (94.1%
      versus 42.3%, p = 0.001) and suicidal plans (64.7% versus 15.4%, p = 0.002).
      Occurrence of psychiatric hospitalization was higher in psychotic BP patients
      compared to non-psychotic BP patients (82.4% versus 46.2%, p = 0.018).
      CONCLUSIONS: Psychotic symptoms in pediatric BP patients are associated with
      suicidal ideation and plans, and psychiatric hospitalizations. Psychotic symptoms
      are a risk factor for suicidality amongst pediatric BP patients.

PMID- 16445990
TI  - Single, intense prenatal stress decreases emotionality and enhances learning
      performance in the adolescent rat offspring: interaction with a brief, daily
      maternal separation.
AB  - Perinatal manipulations can lead to neurobehavioural changes in the progeny. In
      this study we investigated, in adolescent male rat offspring, the consequences of
      a single, intense prenatal stress induced by a 120 min-maternal immobilization at
      gestational day 16, and of a daily, brief maternal separation from postnatal day
      2 until 21, on: unconditioned fear/anxiety-like behaviour in open field and in
      elevated plus-maze; learning performance in the "Can test", a non-aversive
      spatial and tactile/visual task; corticosterone plasma levels under basal and
      stress-induced conditions. Our results indicate that both prenatal stress and
      maternal separation procedures decrease emotionality and enhance learning
      performance. Maternal separation potentiates prenatal stress-induced effects in
      enhancing learning performance. Both basal and stress-induced corticosterone
      plasma levels are reduced following prenatal stress, maternal separation and the
      combination of two procedures. These findings suggest that a single, intense
      prenatal stress can enhance the adaptive stress-related responses in the progeny,
      probably due to the involvement of maternal factors. The synergistic effect of
      prenatal stress and maternal separation on learning performance may be due to a
      further damping of hypothalamic-pituitary-adrenal axis response in the progeny
      that better cope with the task administered.

PMID- 16445991
TI  - Cerebral processing of food-related stimuli: effects of fasting and gender.
AB  - To maintain nutritional homeostasis, external food-related stimuli have to be
      evaluated in relation to the internal states of hunger or satiety. To examine the
      neural circuitry responsible for integration of internal and external
      determinants of human eating behaviour, brain responses to visual and complex
      gustatory food-related stimuli were measured using functional magnetic resonance
      imaging in 18 healthy non-smokers (10 women, 8 men). Each individual was studied
      on two occasions, the order of which was counterbalanced; after eating as usual
      and after 24 h fasting. Raised plasma free fatty acids and lower insulin and
      leptin concentrations confirmed that participants fasted as requested. When
      fasted, participants reported more hunger, nervousness and worse mood and rated
      the visual (but not gustatory) food-related stimuli as more pleasant. The effect
      of fasting on hunger was stronger in women than in men. No circuitry was
      identified as differentially responsive in fasting compared to satiety to both
      visual and gustatory food-related stimuli. The left insula response to the
      gustatory stimuli was stronger during fasting. The inferior occipito-temporal
      response to visual food-related stimuli also tended to be stronger during
      fasting. The responses in the occipito-temporal cortex to visual and in the
      insula to gustatory stimuli were stronger in women than in men. There was no
      interaction between gender and fasting. In conclusion, food reactivity in
      modality-specific sensory cortical areas is modulated by internal motivational
      states. The stronger reactivity to external food-related stimuli in women may be
      explored as a marker of gender-related susceptibility to eating disorders.

PMID- 16445992
TI  - Comparison of activity of individual pyramidal tract neurons during balancing,
      locomotion, and scratching.
AB  - Neuronal mechanisms of the spinal cord, brainstem, and cerebellum play a key role
      in the control of complex automatic motor behaviors-postural corrections,
      stepping, and scratching, whereas the role of the motor cortex is less clear. To
      assess this role, we recorded fore and hind limb-related pyramidal tract neurons
      (PTNs) in the cat during postural corrections and during locomotion; hind limb
      PTNs were also tested during scratching. The activity of nearly all PTNs was
      modulated in the rhythm of each of these motor patterns. The discharge frequency,
      averaged over the PTN population, was similar in different motor tasks, whereas
      the degree of frequency modulation was larger during locomotion. In individual
      PTNs, a correlation between analogous discharge characteristics (frequency or its
      modulation) in different tasks was very low, suggesting that input signals to
      PTNs in these tasks have a substantially different origin. In about a half of
      PTNs, their activity in different tasks was timed to the analogous
      (flexor/extensor) parts of the cycle, suggesting that these PTNs perform similar
      functions in these tasks (e.g., control of the value of muscle activity). In
      another half of PTNs, their activity was timed to opposite parts of the cycle in
      different tasks. These PTNs seem to perform different motor functions in
      different tasks, or their targets are active in different parts of the cycle in
      these tasks, or their effects are not directly related to the control of motor
      output (e.g., they modulate transmission of afferent signals).

PMID- 16445993
TI  - Memory reactivation, dissociated from behavioural expression, decreases ERK
      phosphorylation in the rat prefrontal cortex and amygdala.
AB  - The involvement of MAPK pathways in retrieval was investigated in a situation
      where reactivation of memory was dissociated from its behavioural expression. In
      rats trained in a brightness avoidance discrimination task, exposure to the
      discriminative stimulus had behavioural and molecular consequences: a
      facilitation of the retention performance and a decrease in ERK phosphorylation
      in the prefrontal cortex and amygdala, but not in the hippocampus. These results
      indicate that reactivation processes engage a down-regulation of ERK, possibly
      related to increases in glucocorticoids, in the amygdala and prefrontal cortex
      already known to be involved in emotional retrieval.

PMID- 16445994
TI  - Arsenic exposure alters hepatic arsenic species composition and stress-mediated
      gene expression in the common killifish (Fundulus heteroclitus).
AB  - In the present paper, we examine how arsenic species accumulate in fish liver and
      explore the hypothesis that sublethal arsenic concentrations in fish hepatic
      tissue interfere with stress-mediated gene expression. We exposed killifish
      (Fundulus heteroclitus) to 787 or 0 microg/L arsenic in tank water for 2 weeks.
      Arsenic exposure elevated total liver arsenic from 3.4 microg/g wet weight
      (control fish) to 9.6 microg/g wet weight, and resulted in a higher relative
      proportion of toxic (e.g. monomethylarsenous acid, dimethylarsenous acid, arsenic
      V) versus benign (arsenobetaine) arsenic species in this tissue. Following the
      exposure period, arsenic-treated and control fish were then subjected to a stress
      protocol: confinement and mechanical chasing for 15 min every 3 h. Liver tissue
      and blood were sampled from fish not exposed to the stressor at time 0, and at 8,
      12, 24 and 40 h following the first stressor. Concentrations of the stress
      hormone cortisol increased significantly, and glucocorticoid receptor mRNA levels
      increased and then decreased in both groups, but patterns were nearly identical
      between arsenic pre-treated and arsenic untreated fish. Prior arsenic exposure
      prevented the stress-induced increases in stress-responsive LDH-B mRNA levels and
      enzyme activity observed in fish that had not been exposed to arsenic. However,
      in another stress-responsive gene, PEPCK, arsenic did not interfere with the
      stress-induced increase in gene expression, suggesting that the effects of
      arsenic on stress-mediated gene expression are complex and may involve regulatory
      pathways that differ between these two genes.

PMID- 16445995
TI  - Interactions of chromogranin A-derived vasostatins and monolayers of
      phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine.
AB  - Vasostatin-I (CgA1-76) is a naturally occurring and biologically active N
      terminal peptide derived from chromogranin A (CgA), produced and secreted at high
      concentrations by neuroendocrine tissues and also from a range of neuroendocrine
      tumors. This study aims to examine the hypothesis that in the absence of
      classical protein receptors CgA1-76 may, like its two derived peptides CgA1-40
      and CgA47-66, perturb the lipid microenvironment of other membrane receptors, as
      a basis for the largely inhibitory activities of these CgA peptides. The nature
      of the interactions between phospholipids and vasostatin-derived fragments was
      studied in the Langmuir film balance apparatus at 37 degrees C. The synthetic
      peptides CgA1-40 and CgA47-66 and a recombinant fragment (VS-I) containing
      vasostatin-I (Ser-Thr-Ala-CgA1-78) were compared for their effects on monolayers
      of phosphatidylcholine and phosphatidylethanolamine from pig brain and defined
      species of phosphatidylserine. Marked differences in surface pressure-area
      isotherms and phase-transition plateaus were apparent with the three classes of
      phospholipids on VS-I, CgA1-40 and CgA47-66 in physiological buffer or pure
      water. The results indicate that VS-I and CgA47-66 at 5-10 nM concentrations may
      engage in electrostatic as well as hydrophobic interactions with membrane
      relevant phospholipids at physiological conditions, VS-I in particular enhancing
      the fluidity of saturated species of phosphatidylserine.

PMID- 16445996
TI  - Identification and characterization of the variants of metastasis-associated
      protein 1 generated following alternative splicing.
AB  - The metastasis-associated gene 1 (mta1) was identified initially in rat highly
      metastatic cancer cell lines and found to be a component of the nucleosome
      remodeling and histone deacetylase (NuRD) complex. The gene for mouse mta1 was
      screened and its genomic structure was determined. It consists of 21 exons
      spanning 40 kb of genomic DNA. The full-length mouse Mta1 cDNA contained a 2145
      nucleotide open reading frame encoding 715 amino acids. In addition to the full
      length cDNA, several alternative splicing variants were found. Some differences
      in the splicing variants found were observed among various mouse organs and cells
      examined by the semi-quantitative reverse transcriptase polymerase chain reaction
      (RT-PCR). The cDNAs of the splicing variants were inserted into green fluorescent
      protein (GFP) expression vector and the subcellular localization of the GFP-Mta1
      fusion proteins were analyzed. Knowledge of the Mta1 gene expression pattern will
      be useful in better understanding its functional diversity.

PMID- 16445997
TI  - Altered subcellular distribution of IRS-1 and IRS-3 is associated with defective
      Akt activation and GLUT4 translocation in insulin-resistant old rat adipocytes.
AB  - Insulin receptor signal transduction depends on the precise intracellular
      localization of signalling molecules. This study examines the
      compartmentalization and the insulin-induced translocation and tyrosine
      phosphorylation of insulin receptor substrates (IRS-1 and IRS-3) in epididymal
      white adipose tissue from adult and insulin-resistant old rats. We found that
      insulin induces the translocation of IRS-1 from plasma membrane (PM) and light
      microsomes (LM) to cytosol, whereas IRS-3 translocates from PM to LM and cytosol
      upon insulin stimulation. Old rat adipocytes are characterized by higher relative
      levels of IRS proteins, under basal conditions, in those fractions where they are
      intended to translocate in response to insulin and exhibit a higher
      phosphotyrosine content of IRS-1 and -3 in basal conditions and a lower maximal
      phosphorylation in response to insulin. Furthermore, old rat adipocytes are also
      characterized by a reduced ability of insulin to stimulate both, Akt/PKB activity
      and translocation of GLUT4 to the PM. We conclude that the lower stimulation of
      downstream insulin signalling involved in glucose metabolism in old rat
      adipocytes may be explained, at least in part, by the altered subcellular
      distribution of IRS-1 and -3 proteins. In addition, our data suggest that the
      mechanism of turning on/off insulin receptor-mediated signal is impaired with
      aging.

PMID- 16445998
TI  - Competitive bioreactor hens on the horizon.
AB  - The hen has long held promise as a low-cost, high-yield bioreactor for the
      production of human biopharmaceuticals in egg whites using genetic engineering.
      Two separate reports have recently appeared indicating the production of
      substantial levels of human monoclonal and single chain antibodies (>3 mg and
      >150 mg, respectively) in eggs of transgenic hens. These promising findings
      indicate that the hen is close to becoming a competitive manufacturing platform
      for the production of human biopharmaceuticals.

PMID- 16446000
TI  - Non-NMDA and NMDA receptors are involved in suprathreshold excitation of network
      of frog tectal neurons by a single retinal ganglion cell.
AB  - NMDA receptors play an important functional role in the neuron excitability and
      plasticity. The conditions and consequences of their activation are of interest
      for many neuroscientists. This investigation was designed to explore an
      activation of the NMDA receptors of frog tectal neurons in vivo by a burst of
      spikes of individual retinotectal fiber. We show that: (1) the NMDA receptors of
      tectal neurons can be activated by an intense burst discharge of an individual
      ganglion cell (likely darkness detector) at physiological conditions. (2)
      Activation of the NMDA receptors is achieved, primarily, due to temporal
      summation and frequency facilitation of the fast non-NMDA synaptic potentials.
      However, it is very likely that spatial summation of the fast retinotectal
      synaptic potentials with excitatory synaptic potentials of recurrent connections
      contributes to elicit the NMDA response. (3) The activation of NMDA receptors
      causes a higher level of activity of tectal neuron network. The suprathreshold
      excitation of efferent tectal neurons is characteristic for this level.
      Therefore, the burst discharge of only single retinal ganglion cell can activate
      the tectobulbospinal tract and lead to the motor reaction.

PMID- 16445999
TI  - Influence of connective tissue diseases on the expression of radiation side
      effects: a systematic review.
AB  - BACKGROUND AND PURPOSE: Patient related co-factors may increase the risk of
      radiation morbidity. Connective tissue diseases (CTD) are among the co
      morbidities that are relatively well studied and have been shown to be of
      potential clinical relevance for radiotherapy. The aim of this systematic review
      is to quantify the contribution of CTD to the risk of radiation related side
      effects. PATIENTS AND METHODS: Relevant publications reporting the outcome of
      radiotherapy in patients with CTD were retrieved according to a standardized
      query and evaluated for their methodology and quality of reporting, using defined
      quality criteria. A quantitative estimate of the relative risk of developing side
      effects in patients with CTD was derived from the observed proportions of
      responders in patients with or without CTD. Risk estimates were synthesized
      across studies. RESULTS: Eight studies which include data of 9-209 patients who
      had CTD and were treated with radiotherapy were identified and reviewed. Three of
      these studies included data suited for further quantitative analysis. The test of
      the uni-directional hypothesis that patients with CTD had an increased risk of
      late effects after radiotherapy reached statistical significance, the one-tailed
      P-value being 0.03. The pooled relative risk was 2.0 with 95% confidence interval
      (0.99, 4.1). CONCLUSIONS: CTD is associated with an increased risk of late
      radiation induced normal tissue reaction. The literature published to date
      provides some support for this assertion although most of the reports are plagued
      by methodological weaknesses, thus calling for a large coordinated study.

PMID- 16446001
TI  - Thermostabilization of Bacillus amyloliquefaciens alpha-amylase by chemical cross
      linking.
AB  - Chemical cross-linking of a mesophilic alpha-amylase from Bacillus
      amyloliquefaciens (BAA) was carried out. Intra-molecular cross-links between
      lysine residues upon treatment of the enzyme with ethylene glycol bis(succinic
      acid N-hydroxy succinimide ester) resulted in enhancement of thermostability as
      indicated by irreversible thermoinactivation experiments. Enhancement of
      thermostability coincided with a dramatic protection against aggregation,
      combined with a decrease in surface hydrophobicity. Deamidation, another
      important mechanism of irreversible thermoinactivation, was also diminished upon
      modification. While no significant changes in the kinetic parameters are evident,
      rigidification of the protein structure is suggested by circular dichroism (CD)
      and fluorescence studies.

PMID- 16446002
TI  - Purification and characterisation of an intracellular enzyme with beta
      glucosidase and beta-galactosidase activity from the thermophilic fungus
      Talaromyces thermophilus CBS 236.58.
AB  - An intracellular beta-glycoside hydrolase with beta-glucosidase and beta
      galactosidase activity, designated beta-glucosidase BGL1, was isolated to
      apparent homogeneity from the thermophilic ascomycete Talaromyces thermophilus
      CBS 236.58. The monomeric enzyme has a molecular mass of 50 kDa (SDS-PAGE) and an
      isoelectric point of 4.5-4.6. The enzyme is active with both glucosides such as
      cellobiose and galactosides including lactose; based on the catalytic
      efficiencies determined glucosides are the preferred substrates. beta
      Galactosidase activity of BGL1 is activated by various mono and divalent cations
      including Na+, K+ and Mg2+, and it is moderately inhibited by its reaction
      products glucose and galactose. Its pH optimum for the hydrolysis of galactosides
      is in the range of 5.5-6.0, and its optimum temperature was found to be 50
      degrees C (15 min assay). In addition to its hydrolytic activity, BGL1 shows a
      significant transferase activity which results in the formation of galacto
      oligosaccharides. These have recently attracted interest because of possible
      applications in food industry. The highest yields of oligosaccharides was
      approximately 20% when using 38 gl(-1) lactose as the starting material.

PMID- 16446003
TI  - Culture of skin cells in 3D rather than 2D improves their ability to survive
      exposure to cytotoxic agents.
AB  - In this study, we asked the question of whether cells in 3D culture cope more
      effectively with cytotoxic agents than cells in 2D. The sensitivities of human
      skin cells (keratinocytes, dermal fibroblasts and endothelial cells) to oxidative
      stress (hydrogen peroxide) and to a potentially toxic heavy metal (silver) when
      cultured under 2D and 3D conditions were investigated. The results show a marked
      resistance of cells to a given dose of hydrogen peroxide or silver nitrate
      causing a 50% loss of viability in 3D cultures, when compared to the same cells
      grown in 2D. There was also an improvement in the ability of cells to withstand
      both stresses when cells were in co-culture rather than in mono-culture. Foetal
      calf serum was found to have a mild protective effect in 2D culture but this was
      not extended to findings in 3D culture. This study suggests that dermatotoxicity
      testing using 3D co-cultures might be more likely to reflect true physiological
      responses to xenobiotic materials than existing models that rely on 2D mono
      cultures.

PMID- 16446004
TI  - Transglutaminase-catalyzed site-specific glycosidation of catalase with aminated
      dextran.
AB  - An enzymatic approach, based on a transglutaminase-catalyzed coupling reaction,
      was investigated to modify bovine liver catalase with an end-group aminated
      dextran derivative. We demonstrated that catalase activity increased after
      enzymatic glycosidation and that the conjugate was 3.8-fold more stable to
      thermal inactivation at 55 degrees C and 2-fold more resistant to proteolytic
      degradation by trypsin. Moreover, the transglutaminase-mediated modification also
      improved the pharmacokinetics behavior of catalase, increasing 2.5-fold its
      plasma half-life time and reducing 3-fold the total clearance after its i.v.
      administration in rats.

PMID- 16446005
TI  - A novel deletion in the LTR region of a Greek small ruminant lentivirus may be
      associated with low pathogenicity.
AB  - Greek small ruminant lentivirus (SRLV) strains remain relatively uncharacterized
      at the molecular level, despite the fact that lentiviral diseases of small
      ruminants are known to be widespread in the country. In the present study, we
      investigated the sequence diversity of the LTR region in Greek SRLV strains from
      sheep with and without disease symptoms, since sequence differences within this
      genomic area have been shown to lead to SRLVs with distinct replication rates.
      The AP-4 and AML (vis) motifs and the TATA-box were highly conserved among Greek
      strains, whereas the two AP-1 sites exhibited some substitutions. Pairwise
      comparisons with reference strains revealed that Greek LTR sequences were closer
      to the ovine strains (25.7% average divergence) rather than the caprine strain
      CAEV (59.1% average divergence). The most striking difference observed between
      the two groups of animals was a 13-14 nucleotide deletion in the strains obtained
      from the asymptomatic sheep. The deletion was located within the R region of LTR,
      which was also found to be much less homologous (39.6% average divergence) than
      the U3 and U5. Taken together, our data suggest that the R region of LTR may be
      involved in virus transcriptional activation. Furthermore, a specific deletion
      within this region may, at least in part, be associated with low pathogenicity of
      some SRLV strains.

PMID- 16446006
TI  - Modulated release metoprolol succinate formulation based on ionic interactions:
      in vivo proof of concept.
AB  - A modulated release, multiunit oral drug delivery technology using a system based
      on ionic interactions of anions of salts with quaternary ammonium ions of the
      ammoniomethacrylate polymer is described. The system consisted of a drug layered,
      EUDRAGIT NE-coated salt core which was further coated with EUDRAGIT RS. The
      relative effects of different anions on the polymer permeability have been
      investigated by studying their influence on the in vitro drug release. A
      prototype formulation of metoprolol succinate using this technology was developed
      and the drug release from the formulation was adjusted to have a release profile
      which would match the circadian rhythm i.e. a higher amount of drug would be
      available after an initial lower release (accelerated type of release). The
      formulation was tested in vivo in 12 healthy human volunteers in an open label,
      randomized, two-treatment, two-period, single dose crossover bio-study with
      reference formulation Beloc-zok. The in vivo release demonstrated that compared
      to the reference, a higher amount of drug was available in the plasma from the
      7th hour onwards. A higher AUC of the drug was also observed compared to the
      reference formulation. An in vitro-in vivo correlation was attempted to identify
      a bio-relevant in vitro dissolution medium for the formulation.

PMID- 16446007
TI  - Effect of PLC on functional parameters and oxidative profile in type 2 diabetes
      associated PAD.
AB  - OBJECTIVE: To investigate the effects of propionyl l-carnitine (PLC) on clinical
      and functional parameters, and markers of the overall oxidation state in patients
      with peripheral arterial disease (PAD) associated with non-insulin-dependent
      diabetes mellitus (NIDDM). DESIGN AND SETTING: Randomised, double-blind, clinical
      trial, conducted in the Unit of Medical Angiology of the University of Catania.
      PATIENTS AND INTERVENTIONS: Seventy-four patients with NIDDM-associated PAD were
      treated with PLC (2 g/day) or placebo for 12 months. MAIN OUTCOME MEASURES:
      Ankle/brachial index (ABI) and the distance of pain-free walking were evaluated
      at baseline, 6 and 12 months. Malondialdehyde, 4-hydroxynonenal, oxidation time
      of low-density lipoproteins, and nitrite/nitrate ratio were measured as indices
      of the overall oxidation profiles at baseline and 12 months. RESULTS: In the PLC
      group, ABI progressively increased (0.78, 0.83, and 0.88 at 0, 6 and 12 months,
      respectively). The distance of pain-free walking also improved (366.4, 441.9 and
      519.8 m, respectively). In the placebo group, these parameters were relatively
      unchanged. Significant improvements in all parameters of the oxidative profile
      were seen in the PLC-treated group, with only minor variations observed in the
      placebo group. CONCLUSIONS: These results suggest that adjunct therapy with PLC
      may be warranted in type 2 diabetes-associated PAD.

PMID- 16446008
TI  - Cervicofacial necrotizing fasciitis.
AB  - Cervical necrotizing fasciitis is a fast spreading acute soft tissue
      inflammation. Death can occur within 12-24 h. Early identification and treatment
      is needed. We report the case of a 75 year old woman with diabetes and high
      cholesterol, adipositas who developed cervical necrotizing fasciitis of
      odotongenic origin with massive subcutaneous air collection and first sign of
      septicaemia. Surgical treatment with debridement and drainage in combination with
      intravenous broadbased antibiotics as well as daily irrigation of the wound with
      iodine solution (Betaisodona) and metronidazol (local antibiotic treatment) was
      performed. The patient recovered completely. Surgical debridement combined with
      broad-spectrum of antibiotics showed satisfying result for the management of
      cervical necrotizing fasciitis of dentogenous origin.

PMID- 16446009
TI  - Enhancement of serum lipoprotein lipase mass levels by intensive insulin therapy.
AB  - We previously reported that lipoprotein lipase mass level in preheparin serum
      (preheparin LPL mass) was significantly lower in type 2 diabetes mellitus
      compared to healthy subjects and increased by conventional insulin therapy using
      NPH (intermediate-acting) insulin. The aim of this study was to investigate the
      effects of intensive insulin therapy on preheparin LPL mass. Thirty-two subjects
      (total group) with type 2 diabetes receiving treatment by NPH insulin injection
      twice a day in the morning and evening were switched to basal bolus insulin (BBI)
      therapy (fast-acting insulin after each meal and NPH insulin before bedtime). In
      14 subjects, the total daily insulin dose was not change after switching to BBI
      therapy (iso-dose group). After 3 months of BBI therapy, preheparin LPL mass
      increased significantly from 47 to 56 ng/ml in total group. Glycosylated
      hemoglobin and serum triglyceride levels decreased significantly, and high
      density lipoprotein-cholesterol increased significantly. Low-density lipoprotein
      levels did not changed but increase in size was suggested by PAG disc
      electrophoresis. Similar changes were observed in the iso-dose group. These
      results suggest that BBI therapy enhances preheparin LPL mass, accompanied by
      antiatherogenic changes in glucose and lipid metabolism.

PMID- 16446010
TI  - Genomics of microRNA.
AB  - Discovered just over a decade ago, microRNA (miRNA) is now recognized as one of
      the major regulatory gene families in eukaryotic cells. Hundreds of miRNAs have
      been found in animals, plants and viruses, and there are certainly more to come.
      Through specific base-pairing with mRNAs, these tiny approximately 22-nt RNAs
      induce mRNA degradation or translational repression, or both. Because a miRNA can
      target numerous mRNAs, often in combination with other miRNAs, miRNAs operate
      highly complex regulatory networks. In this article, we summarize the current
      status of miRNA gene mining and miRNA expression profiling. We also review up-to
      date knowledge of miRNA gene structure and the biogenesis mechanism. Our focus is
      on animal miRNAs.

PMID- 16446011
TI  - Synthesis and receptor binding studies of 3-substituted piperazine derivatives.
AB  - In order to find novel receptor ligands various substituents were introduced into
      the side chain in position 3 of the piperazine 5. During nucleophilic
      substitution of the hydroxy group of 5 aziridinium ions were formed, resulting in
      rearranged 1,4-diazepanes and piperazines as side products. 1,2-anellated
      piperazines 15, 18 and 19 were prepared by hydrogenation of the alpha,beta
      unsaturated ester 13 and by condensation of the primary amine 16b with
      formaldehyde, respectively. Receptor binding studies with radioligands revealed
      that the phenylacetamide 17b interacts with moderate affinity (K(i) = 181 nM) and
      considerable selectivity with sigma(1) receptors.

PMID- 16446013
TI  - Novel vaccines for the treatment of chronic HBV infection based on mycobacterial
      heat shock protein 70.
AB  - Immunogenic peptide-based vaccines can raise significant cellular immune
      responses. Although cytotoxic T lymphocytes (CTL) peptide epitopes are generally
      poor immunogens, heat shock protein 70 from Mycobacterium tuberculosis (TBhsp70)
      can overcome this problem since it is a potent adjuvant that links innate and
      adaptive immune responses. Our goal is to use TBhsp70 as an adjuvant for
      development of therapeutic vaccines for chronic Hepatitis B virus infection
      (HBV). To this end, we genetically fused the HBV core 18-27 peptide (HBcAg((18
      27))) as a CTL epitope to the C-terminus of TBhsp70 and expressed the resulting
      protein in methylotropic yeast Pichia pastoris GS115. At the same time, the
      TBhsp70-HBcAg((18-27)) peptide complex was reconstituted in vitro. We
      investigated whether TBhsp70-peptide complex and TBhsp70-peptide fusion protein
      could generate antigen specific CTL responses in vitro. Dendritic cells (DC) from
      HLA-A2(+) chronic HBV infection and healthy control pulsed with two vaccines were
      studied phenotypically by FACS analyses and functionally by cytokine release, and
      HBV-specific CTL response. Our results demonstrate that two vaccines can activate
      DC of chronic HBV infection and healthy control by upregulation CD40 and CD86,
      high production of IL-12p70 and TNF-alpha. Furthermore, autologous T cells with
      DC stimulated by two vaccines can produce IFN-gamma and generate HBV-specific CTL
      response. However, capacity for CTL response and cytokines production from HBV
      infections remained inferior to that of healthy controls. Thus, the strategy of
      utilizing TBhsp70 may provide a novel design for the development of prophylactic
      and therapeutic vaccines.

PMID- 16446012
TI  - Strong systemic and mucosal immune responses to surface-modified PLGA
      microspheres containing recombinant hepatitis B antigen administered
      intranasally.
AB  - Surface-modified DL-lactide/glycolide copolymer (PLGA) microspheres with chitosan
      (CS) were developed for nasal immunization using recombinant Hepatitis B (HBsAg)
      surface protein for the induction of humoral, cellular and mucosal immunity.
      Modified PLGA microspheres were characterized in vitro for their size, shape,
      entrapment efficiency and zeta potential. The nasal clearance rate was evaluated
      by gamma scintigraphy in rabbits. The antigen integrity, in vitro release and its
      stability at 37 degrees C were also evaluated. The designed cationic microspheres
      possessed 27.2 mV zeta potential and an average size less than 10 microm with
      antigen loading efficiency of 80+/-5%. However, zeta potential of unmodified PLGA
      microspheres was measured to be negative (-8.7 mV). The modified PLGA
      microspheres showed the lowest nasal clearance rate when compared with unmodified
      PLGA microspheres and lactose powder. The antigen integrity was retained intact
      in encapsulated form as well as on release. The immune-stimulating activity was
      studied by measuring anti-HBsAg titre, secretory IgA level in serum, vaginal,
      nasal and salivary secretions (mucosal secretions) and cytokine level
      (interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)) in spleen homogenates
      following nasal administration of modified PLGA microspheres in Balb/c mice and
      compared with alum-HBsAg vaccine injected subcutaneously. The serum anti-HBsAg
      titre obtained after nasal administration of modified PLGA microspheres was
      comparable with titre recorded after alum-HBsAg was administered subcutaneously.
      Moreover, alum-HBsAg vaccine did not elicit sIgA in mucosal secretions as it was
      induced and measured in the case of nasal administration of modified PLGA
      microspheres. Similarly, there was no cellular response (cytokine level) in case
      of alum-HBsAg vaccine. Modified PLGA microspheres (cationic microspheres) thus
      produced humoral (both systemic and mucosal) and cellular immune responses upon
      nasal administration. These data demonstrate high potential of modified PLGA
      microspheres for their use as a carrier adjuvant for nasal subunit vaccines.

PMID- 16446014
TI  - Immunity and correlates of protection for rotavirus vaccines.
AB  - Rotaviruses are the most common cause of severe, dehydrating diarrhea in children
      worldwide. The tremendous global incidence of rotavirus gastroenteritis,
      especially in developing countries, emphasizes the need for vaccines to prevent
      associated morbidity and mortality. However, immunity to rotavirus is not
      completely understood. At this time, total serum RV IgA, measured shortly after
      infection, appears to be the best marker of protection against rotavirus. This
      review describes the current understanding of rotavirus immunity, including
      mechanisms of protection against rotavirus from selected animal models, and
      correlates of protection associated with natural infection or vaccination from
      humans.

PMID- 16446015
TI  - Enhanced mucosal immunogenicity of prion protein following fusion with B subunit
      of Escherichia coli heat-labile enterotoxin.
AB  - Mucosal vaccine against prion protein (PrP), a major component of prions, is
      urgently awaited since the oral transmission of prions from cattle to humans is
      highly suspected. In the present study, we produced recombinant bovine and mouse
      PrPs fused with or without the B subunit of Escherichia coli heat-labile
      enterotoxin (LTB) and intranasally immunized mice with these fused proteins.
      Fusion with LTB markedly enhanced the mucosal immunogenicity of bovine PrP,
      producing a marked increase in specific IgG and IgA titer in serum. Mouse PrP
      also showed slightly increased immunogenicity following fusion with LTB. These
      results demonstrate that LTB-fused PrPs might be potential candidates for
      protective mucosal prion vaccines.

PMID- 16446016
TI  - DNA vaccines co-expressing GP5 and M proteins of porcine reproductive and
      respiratory syndrome virus (PRRSV) display enhanced immunogenicity.
AB  - The two major membrane-associated proteins of porcine reproductive and
      respiratory syndrome virus (PRRSV), GP5 and M (encoded by ORF5 and ORF6 genes,
      respectively), are associated as disulfide-linked heterodimers (GP5/M) in the
      virus particle. In the present study, three different DNA vaccine constructs,
      expressing GP5 alone (pCI-ORF5), M alone (pCI-ORF6) or GP5 and M proteins
      simultaneously (pCI-ORF5/ORF6), were constructed. In vitro, the co-expressed GP5
      and M proteins could form heterodimeric complexes in transfected cells and
      heterodimerization altered the subcellular localization of GP5. The
      immunogenicities of these DNA vaccine constructs were firstly investigated in a
      mouse model. Mice inoculated with pCI-ORF5/ORF6 developed PRRSV-specific
      neutralizing antibodies at 6 and 8 weeks after primary immunization. However,
      only some mice developed low levels of neutralizing antibodies in groups
      immunized with pCI-ORF5 or pCI-ORF6. The highest lymphocyte proliferation
      responses were also observed in mice immunized with pCI-ORF5/ORF6. Interestingly,
      significantly enhanced GP5-specific ELISA antibody could be detected in mice
      immunized with pCI-ORF5/ORF6 compared to mice immunized with pCI-ORF5. The
      immunogenicities of pCI-ORF5/ORF6 were further evaluated in piglets (the natural
      host) and all immunized piglets developed neutralizing antibodies at 10 weeks
      after primary immunization, whereas there was no detectable neutralizing
      antibodies in piglets immunized with pCI-ORF5. These results indicate that the
      formation of GP5/M heterodimers may be involved in post-translational
      modification and transport of GP5 and may play an important role in immune
      responses against PRRSV infection. More importantly, co-expression of GP5 and M
      protein in heterodimers can significantly improve the potency of DNA vaccination
      and could be used as a strategy to develop a new generation of vaccines against
      PRRSV.

PMID- 16446018
TI  - Gesture standardization increases the reproducibility of 3D kinematic
      measurements of the knee joint.
AB  - BACKGROUND: The literature on the 3D kinematics of the knee suggests that the
      gesture accomplished during kinematic assessment might play a significant role in
      the values measured. The purpose of this study is to demonstrate that a
      standardized gesture leads to an increased reproducibility in 3D kinematic
      measurements of the knee. METHODS: Seventeen healthy male subjects performed
      series of knee-bends in standardized and unconstrained conditions while their
      left knee's 3D kinematics were recorded using an optical motion-recording system.
      Standardized knee-bends were performed in a specially designed structure
      stabilizing the shoulders, pelvis and feet. Coefficient of multiple correlation
      were calculated for the ascent and the descent phases of the knee-bends for the
      tibial rotation and abduction/adduction components of the knee movement.
      FINDINGS: Comparisons between coefficient of multiple correlation of the
      different gesture conditions showed a statistically significant increase in
      reproducibility for the tibial rotation during the standardized knee-bends.
      INTERPRETATION: It appears that gesture standardization is an interesting option
      to consider for precise kinematic assessment of the living human knee.

PMID- 16446017
TI  - Vaccination of mice against intestinal Trichinella spiralis infections by oral
      administration of antigens microencapsulated in methacrilic acid copolymers.
AB  - BALB/c and NIH mice have been successfully vaccinated against the intestinal
      nematode Trichinella spiralis by oral administration of crude larval extracts
      (CLE) and excretory-secretory (ES) products derived from first stage T. spiralis
      larvae (L1) encapsulated in microcapsules made of copolymers of the metacrylic
      acid (Eudragit L100). Oral vaccination stimulated the secretion of IFN-gamma and
      inhibited the secretion of IL-4 in spleen and mesenteric lymph nodes (MLN) of
      BALB/c mice. In vaccinated mice the proportion of CD4+ cells increased (p<0.05)
      in Peyer's patches (PP) and decreased (p<0.05) in spleen whereas the proportion
      of CD19+ cells decreased (p<0.05) in both PP and spleen, with regard to
      unvaccinated controls. No variation was evident for the proportion of CD8+ cells.
      Oral vaccination elevated the antigen-specific serum IgG1 and IgA (p<0.05) as
      well as the antigen-specific IgA response in MLN (p<0.05). It is concluded that
      this way of vaccination induced a concurrent Th1/ Th2 local and systemic
      responses that are protective and at the same time they may help balancing the
      strong Th2 response triggered by helminth infections.

PMID- 16446019
TI  - An MRI investigation of intervertebral disc deformation in response to torsion.
AB  - BACKGROUND: The nucleus pulposus deforms towards an area of least compression in
      response to offset loading, however, there is a lack of data reporting the
      deformation patterns of nuclear material in rotated positions of the lumbar
      spine. Our purpose was to assess a novel methodology using MRI to track nuclear
      deformation in response to flexion and extension positions, and the combined
      positions of flexion with left rotation and extension with left rotation, at L1-2
      and L4-5. METHODS: Three asymptomatic female subjects, mean age 27 years,
      underwent T2 weighted MRI sequences in flexed, extended, and left rotated
      positions combined with flexion and extension. A pixel profile technique was
      employed to determine direction and magnitude of nuclear deformation. RESULTS: In
      5 of 6 discs examined, deformation of the nucleus occurred anteriorly in
      extension and posteriorly in flexion. Left rotation resulted in migration of
      nuclear material to the right in 9 of 12 discs. Of the three discs that
      demonstrated a right nuclear migration, two occurred at L4-5 and one at L1-2.
      INTERPRETATION: This methodology demonstrated that nucleus pulposus deformation
      can be measured reliably in various positions achieved within the confines of the
      MRI. The consistent migration of nuclear material following sagittal plane
      movement and the less consistent response to rotation positions suggest other
      asymmetrical loading on the intervertebral disc may accompany rotation.

PMID- 16446020
TI  - High carbon monoxide concentrations during the rainy season in Campo Grande, in
      central Brazil.
AB  - This work describes an event of unusually large mixing ratios of carbon monoxide,
      CO, observed during a typical rainy season time period in central Brazil, when
      concentrations are expected to be at low levels. CO measurements were performed
      in Campo Grande (20.02 degrees S; 54.5 degrees W), from July 2001 to October
      2002, covering entire periods of the dry and wet seasons. From January to June,
      average CO was 131 parts per billion by volume (ppbv). During November/December,
      average CO is about 180 ppbv. On November 13, 521.9 and 565.6 ppbv were observed.
      It is shown that for this special event, in which there was practically no fire
      activity at or near the site, air parcels reaching the site were enriched with
      fire products from regions much further north, near the equatorial region, where
      the fire activity is delayed in time, compared to central Brazil.

PMID- 16446021
TI  - Mild memory impairment in healthy older adults is distinct from normal aging.
AB  - Mild memory impairment was detected in 28% of a sample of healthy community
      dwelling older adults using the delayed recall trial of a word list learning
      task. Statistical analysis revealed that individuals with memory impairment also
      demonstrated relative deficits on other measures of memory, and tests of
      executive function, processing speed and global cognition, as measured by the
      CERAD and CogState batteries and CANTAB paired associate learning task. These
      relative deficits cannot be explained by age-related changes, education,
      intelligence, mood, health-related factors, or the individuals' ApoEepsilon4
      status. Memory-impaired individuals (n = 30) did not recognize the extent of
      their memory and cognitive difficulties beyond the general complaints expressed
      by normal elderly (n = 77) within the study and their apparent difficulties did
      not appear to impact on their participation in life activities. These findings
      suggest it is unlikely that the memory and cognitive difficulties demonstrated by
      individuals with mild memory impairment reflect normal aging. Rather it is
      possible that such impairment may signal early neurodegenerative processes worthy
      of further investigation.

PMID- 16446022
TI  - The 'hard problem' and the quantum physicists. Part 1: the first generation.
AB  - All four of the most important figures in the early twentieth-century development
      of quantum physics-Niels Bohr, Erwin Schroedinger, Werner Heisenberg and Wolfgang
      Pauli-had strong interests in the traditional mind-brain, or 'hard,' problem.
      This paper reviews their approach to this problem, showing the influence of
      Bohr's complementarity thesis, the significance of Schroedinger's small book,
      'What is life?,' the updated Platonism of Heisenberg and, perhaps most
      interesting of all, the interaction of Carl Jung and Wolfgang Pauli in the
      latter's search for a unification of mind and matter.

PMID- 16446023
TI  - Interpreting event-related brain potential (ERP) distributions: implications of
      baseline potentials and variability with application to amplitude normalization
      by vector scaling.
AB  - Recent proposals regarding the purpose and validity of amplitude normalization by
      vector scaling including mitigation of baseline and noise problems in between
      condition difference analyses are critically evaluated. In so doing, we elaborate
      on some of the points raised in regarding baselines and noise, especially as
      these impact amplitude normalization by vector scaling and discuss the motivation
      for measuring event-related brain potential (ERP) amplitudes relative to a pre
      stimulus baseline and the implications of this for certain (but not all)
      inferences. Throughout, our focus is on the logic of interpreting ERP
      measurements with an emphasis on the importance of specific assumptions and
      consideration of what conclusions are and are not supported.

PMID- 16446024
TI  - Conservative management of preterm premature rupture of membranes between 18 and
      23 weeks of gestation--maternal and neonatal outcome.
AB  - OBJECTIVE: To evaluate the maternal and neonatal outcome of pregnancies after
      preterm premature rupture of membranes (PPROM) between 18 and 23 weeks of
      gestation. STUDY DESIGN: We performed a retrospective analysis of all deliveries
      at the University of Miami/Jackson Memorial Hospital after PPROM between 18 and
      23 weeks of gestation from January 1997 to December 1999. All patients who
      delivered within 12 h of rupture of membranes were excluded. We further analyzed
      the data by dividing the patients into three groups based on the gestational age
      at which PPROM occurred as follows: (1) 18-19 weeks, (2) 20-21 weeks and (3) 22
      23 weeks. For statistical analysis we combined two groups 18-19 weeks and 20-21
      weeks. RESULTS: A total of 66 singleton pregnancies were included in our study.
      Median overall latency period until delivery was 62 h (range 12-654) with
      significantly prolonged latency at 22-23 weeks gestation in comparison to earlier
      gestation. Maternal complications were chorioamnionitis (n=19), placental
      abruption (n=3), retained placenta (n=6) and postpartum hemorrhage (n=5). Twenty
      fetuses were born alive (none between 18 and 19 weeks, 2 between 20 and 21 weeks
      and 18 between 22 and 23 weeks). These infants remained in the nursery between 1
      and 555 days (median 106 days). A total of 12 infants were discharged home alive
      (1 between 20 and 21 weeks, 11 between 22 and 23 weeks). All surviving infants
      suffered at least one major neonatal complication. CONCLUSION: Conservative
      management of PPROM prior to 21 weeks of gestation was associated with very poor
      pregnancy outcome in our study. Although survival improved significantly after 22
      weeks, all infants suffered major neonatal morbidity.

PMID- 16446025
TI  - Atosiban and nifedipine in acute tocolysis: a comparative study.
AB  - OBJECTIVE: The objective was to compare the effectiveness, efficacy, and safety
      of atosiban and nifedipine in preventing or delaying premature labor. DESIGN: An
      interventional, randomized, controlled trial of 63 women experiencing preterm
      labor varying from 24 to 35 completed weeks of gestation. The women were
      randomized to receive either atosiban intravenously (group I, n=31), or
      nifedipine orally (group II, n=32). RESULTS: There were no significant
      differences in effectiveness and efficacy of tocolysis between the two groups.
      Women with a history of preterm labor responded significantly better to atosiban
      than those with no such history. Those at 28 weeks or less responded
      significantly better to nifedipine, while those at more than 28 weeks' gestation
      showed an equal response in the two groups. Nifedipine achieved uterine
      quiescence in a significantly shorter time than atosiban. The maternal side
      effects were higher with nifedipine. Neonatal complications were comparable in
      both groups. CONCLUSIONS: Both drugs are equally effective and efficacious in
      acute tocolysis. Subgrouping of patients according to gestational age and history
      of preterm labor may be applied in selecting the line of treatment. The maternal
      side effects were higher with nifedipine.

PMID- 16446026
TI  - Early pre-eclampsia: what proportion of women qualify for expectant management
      and if not, why not?
AB  - OBJECTIVE: To determine what proportion of women with early pre-eclampsia qualify
      for expectant management and the magnitude of factors excluding this approach.
      STUDY DESIGN: A prospective case series with continuous data capture over one
      year at a tertiary referral centre. All women (n=169) with singleton pregnancies,
      presenting with early (> or =20 and <34 weeks' gestation) pre-eclampsia, were
      admitted, stabilised and evaluated. Major maternal or fetal complications at this
      stage were indications for delivery. However, when the pregnancy was otherwise
      stable, expectant management was commenced if the gestation was >or =24 weeks.
      Termination was offered from 20 to 23 weeks' gestation. RESULTS: Of the 169 women
      admitted, 82 (48.5%) were managed expectantly and 87 (51.5%) delivered after
      stabilisation and evaluation. Early fetal distress (32%) and major maternal
      complications (28%) were the most frequent reasons preventing expectant
      management. Ascites (18%) and HELLP syndrome (13%) ranked highest amongst the
      maternal complications. CONCLUSIONS: In this study, almost half of the women
      presenting with early onset pre-eclampsia qualified for expectant management.
      Early fetal distress was the most frequent reason preventing expectant
      management.

PMID- 16446027
TI  - Physiological volume regulation by spermatozoa.
AB  - Maturing spermatozoa passing through the epididymis experience increasing
      osmolality in the luminal environment and mature cells are stored in fluids hyper
      osmotic to serum. When ejaculated into the female tract, they encounter a hypo
      osmotic challenge which initiates the process of regulatory volume decrease
      (RVD). Defects in RVD result in hindrance of mucus penetration in man and failure
      of utero-tubal passage in mice. Epididymal sperm from the mouse and cynomolgus
      monkey and ejaculated sperm from man and monkey have been isolated and dispersed
      in media with osmolalities mimicking those of uterine fluid or cervical mucus.
      The effects of specific and broad-spectrum ion channel blockers indicate the
      involvement of separate K+ and Cl- channels as well as organic osmolytes in
      physiological sperm RVD, with mechanisms developed during epididymal maturation.
      Western blotting and immuno-cytochemistry identify and localise some of these
      channels which play a crucial role in fertilisation in vivo and could be targets
      for post-testicular contraception.

PMID- 16446028
TI  - Olfactory threshold increase in trigeminal neuralgia after balloon compression.
AB  - Idiopathic trigeminal neuralgia (ITN) is a well-known disease often treated with
      neurosurgical procedures, which may produce sensorial abnormalities, such as
      numbness, dysesthesia and taste complaints. We studied 12 patients that underwent
      this technique, in order to verify pain, gustative and olfactory thresholds
      abnormalities, with a follow-up of 120 days. We compared the patients with a
      matched control group of 12 patients. Our results found a significant difference
      in the olfactory threshold at the immediate post-operative period (p=0.048). We
      concluded that injured trigeminal fibers are probably associated with the
      increase in the olfactory threshold after the surgery, supporting the sensorial
      interaction theory.

PMID- 16446029
TI  - Activation of the hedgehog pathway in a subset of lung cancers.
AB  - Activation of the hedgehog pathway is reported in lung cancer, but its frequency
      remains unknown. We examine activation of this pathway in lung cancers by in situ
      hybridization and immunohistochemstry, and find that less than 10% of the tumors
      have elevated hedgehog target gene expression. We further identify a cell line
      NCI-H209 and two primary tumors with no detectable Su(Fu), a negative regulator
      of the pathway. Ectopic expression of Su(Fu) in NCI-H209 cells down-regulates
      hedgehog target gene expression and leads to inhibition of cell proliferation.
      These data indicate that activation of the hedgehog pathway is activated through
      Shh over-expression or Su(Fu) inactivation in only a subset of lung cancers.

PMID- 16446030
TI  - Expression of aquaporin-9 immunoreactivity by catecholaminergic amacrine cells in
      the rat retina.
AB  - Aquaporins are involved in the maintenance of ionic and osmotic balance in the
      central nervous system and in the eye. Whereas the expression of aquaporin-9
      immunoreactivity in the brain has been described for catecholaminergic neurons
      and glial cells, the expression of aquaporin-9 in the neural retina is unclear.
      We examined the distribution of aquaporin-1 and -9 immunoreactivities in retinas
      of the rat. Aquaporin-9 immunoreactivity was expressed exclusively by tyrosine
      hydroxylase (TH) positive amacrine cells, while aquaporin-1 immunoreactivity was
      expressed by photoreceptor cells and by TH negative amacrine cells. The staining
      pattern of aquaporin-9 did not change up to 4 weeks after pressure-induced
      transient retinal ischemia. It is concluded that catecholaminergic, putatively
      dopaminergic, amacrine cells of the retina express aquaporin-9.

PMID- 16446031
TI  - Temporal course of emotional negativity bias: an ERP study.
AB  - There is considerable evidence that people are especially sensitive to
      emotionally negative materials. However, the temporal course of the negativity
      bias is still unclear. To address this issue, we observed the changes of P2, late
      positive components (LPC) and lateralized readiness potential (LRP) under
      positive, negative and neutral conditions, with International Affective Picture
      System (IAPS) pictures as emotional stimuli. We found that the amplitude of P2 in
      the negative block was significantly larger than that in the positive block,
      indicating that the attentional negativity bias occured very early in emotion
      perception. The LPC amplitude evoked by negative pictures was larger than that by
      positive and neutral pictures, suggesting that the negativity bias also occurred
      in a later evaluation stage of emotion processing. The response-locked LRP
      interval was shortest in the block of negative pictures, indicating that the
      negative contents elicited a reaction priming effect. Above all, this research
      showed that emotional negativity bias could occur in several temporal stages
      distinguished by attention, evaluation and reaction readiness periods.

PMID- 16446032
TI  - Racial distinction of the unknown facial identity recognition mechanism by event
      related fMRI.
AB  - A body of evidence exists indicating that the function of the fusiform area of
      the face is selectively involved in the perception of faces, and in particular,
      in perceiving racial differences. In the present study, we investigated the
      neural substrates of the face-selective region (the fusiform face area, FFA) in
      the ventral occipital-temporal cortex and examined their role in case of same
      racial face recognition by employing event-related fMRI. Twelve healthy subjects
      (Oriental-Koreans) performed the familiarity judgment tasks while they were being
      presented with familiar and unknown faces of Oriental-Koreans and Caucasian
      Americans. The results indicate that there are significant differences in
      perceiving unfamiliar faces between Oriental-Koreans and Caucasian-Americans in
      the FFA, whereas no significant difference was found between familiar Oriental
      Korean and Caucasian-American faces in the same area. This suggests that an
      effect of same-race superiority exists when the perceived identity is only
      unfamiliar. The neural responses to Oriental-Koreans versus Caucasian-Americans
      in Oriental-Korean subjects likely reflect cultural evaluations of social groups
      as modified by individual experience.

PMID- 16446033
TI  - Interpretation of 'energy-filtered electron-diffracted beam holography' by R.A.
      Herring.
AB  - A straightforward application of the theoretical framework presented by Verbeeck
      et al. [Ultramicroscopy 102 (2005) 239] is presented to explain the energy
      filtered electron-diffracted beam holography experiments published by Herring
      [Ultramicroscopy 104 (2005) 261]. It is shown that the theory is in agreement
      with all experimental findings, which leads to the interpretation that the
      experiments are mainly measuring the angular coherence of the source image rather
      than exposing details on the coherence properties of inelastic scattering. A
      change in experimental parameters is proposed, which could result in interesting
      information about the coherence in an inelastic scattering process.

PMID- 16446034
TI  - Canine visceral leishmaniosis: a comparative analysis of the EIE-leishmaniose
      visceral-canina-Bio-Manguinhos and the IFI-leishmaniose-visceral-canina-Bio
      Manguinhos kits.
AB  - This study evaluated the performance of the EIE-leishmaniose-visceral-canina-Bio
      Manguinhos (EIE-LVC) kit and to compare it with that of the IFI-leishmaniose
      visceral-canina-Bio-Manguinhos (IFI-LVC) kit. Four groups of dogs were studied:
      group 1 (G1), dogs with clinical signs indicative of CVL and testing positive for
      the parasite (n = 25); group 2 (G2), dogs with only a presumed diagnosis of CVL
      (n = 62); group 3 (G3), dogs that had never lived in an area where CVL is endemic
      and never received a blood transfusion (n = 16); group 4 (G4), dogs carrying
      other parasites: such as babesiosis (n = 4), ehrlichiosis (n = 6) and demodicosis
      (n = 1). G1 and G3 were used for the calculation of sensitivity and specificity,
      respectively. The EIE-LVC showed a sensitivity of 72% (IC 95%: 50.4-87.1%) and a
      specificity of 87.5% (IC 95%: 60.4-97.8%). The value of the kappa index was 0.975
      (CI 95%: 0.926-1.024), which represents an excellent fit. For IFI-LVC, the
      sensitivity was 68.0% (CI 95%: 46.4-84.3%) and the specificity 87.5% (CI 95%:
      60.4-97.8%). When the tests were conducted in parallel, sensitivity was 92.0% (CI
      95%: 72.5-98.6%) and specificity 75.0% (CI 95%: 47.4-91.7%). However, when
      conducted consecutively, the tests showed a sensitivity of 48.0% (CI 95%: 28.3
      68.2%) and a specificity of 100.0% (CI 95%: 75.9-99.4%). The analysis of
      clinically suspected dogs using IFI-LVC and EIE-LVC kits in parallel, revealed
      that 26/62 animals were positive. Cross-reaction was observed in a dog with
      demodicosis. These results lead to the following conclusions: (1) the performance
      of the EIE-LVC kit is not statistically different from the IFI-LVC and (2) the
      kits must be used in parallel if higher sensitivity is required, reducing the
      number of false-negative results.

PMID- 16446036
TI  - Long saphenous venous cutdown revisited.

PMID- 16446035
TI  - The use of Integra in necrotizing fasciitis.

PMID- 16446037
TI  - Primary visual cortex neurons that contribute to resolve the aperture problem.
AB  - It is traditional to believe that neurons in primary visual cortex are sensitive
      only or principally to stimulation within a spatially restricted receptive field
      (classical receptive field). It follows from this that they should only be
      capable of encoding the direction of stimulus movement orthogonal to the local
      contour, since this is the only information available in their classical
      receptive field "aperture." This direction is not necessarily the same as the
      motion of the entire object, as the direction cue within an aperture is ambiguous
      to the global direction of motion, which can only be derived by integrating with
      unambiguous components of the object. Recent results, however, show that primary
      visual cortex neurons can integrate spatially and temporally distributed cues
      outside the classical receptive field, and so we reexamined whether primary
      visual cortex neurons suffer the "aperture problem." With the stimulation of an
      optimally oriented bar drifting across the classical receptive field in different
      global directions, here we show that a subpopulation of primary visual cortex
      neurons (25/81) recorded from anesthetized and paralyzed marmosets is capable of
      integrating informative unambiguous direction cues presented by the bar ends,
      well outside their classical receptive fields, to encode global motion direction.
      Although the stimuli within the classical receptive field were identical, their
      directional responses were significantly modulated according to the global
      direction of stimulus movement. Hence, some primary visual cortex neurons are not
      local motion energy filters, but may encode signals that contribute directly to
      global motion processing.

PMID- 16446038
TI  - Cross-reinnervation changes the expression patterns of the monocarboxylate
      transporters 1 and 4: An experimental study in slow and fast rat skeletal muscle.
AB  - The monocarboxylate transporters 1 and 4 are expressed in brain as well as in
      skeletal muscle and play important roles in the energy metabolism of both
      tissues. In brain, monocarboxylate transporter 1 occurs in astrocytes,
      ependymocytes, and endothelial cells while monocarboxylate transporter 4 appears
      to be restricted to astrocytes. In muscle, monocarboxylate transporter 1 is
      enriched in oxidative muscle fibers whereas monocarboxylate transporter 4 is
      expressed in all fibers, with the lowest levels in oxidative fiber types. The
      mechanisms regulating monocarboxylate transporter 1 and monocarboxylate
      transporter 4 expression are not known. We hypothesized that the expression of
      these transporters would be sensitive to long term changes in metabolic activity
      level. This hypothesis can be tested in rat skeletal muscle, where permanent
      changes in activity level can be induced by cross-reinnervation. We transplanted
      motor axons originally innervating the fast-twitch extensor digitorum longus
      muscle to the slow-twitch soleus muscle and vice versa. Four months later,
      microscopic analysis revealed transformation of muscle fiber types in the cross
      reinnervated muscles. Western blot analysis showed that monocarboxylate
      transporter 1 was increased by 140% in extensor digitorum longus muscle and
      decreased by 30% in soleus muscle after cross-reinnervation. In contrast, cross
      reinnervation induced a 62% decrease of monocarboxylate transporter 4 in extensor
      digitorum longus muscle and a 1300% increase in soleus muscle. Our findings show
      that cross-reinnervation causes pronounced changes in the expression levels of
      monocarboxylate transporter 1 and monocarboxylate transporter 4, probably as a
      direct consequence of the new pattern of nerve impulses. The data indicate that
      the mode of innervation dictates the expression of monocarboxylate transporter
      proteins in the target cells and that the change in monocarboxylate transporter
      isoform profile is an integral part of the muscle fiber transformation that
      occurs after cross-reinnervation. Our findings support the hypothesis that the
      expression of monocarboxylate transporter 1 and monocarboxylate transporter 4 in
      excitable tissues is regulated by activity.

PMID- 16446039
TI  - Effects of bee venom peptidergic components on rat pain-related behaviors and
      inflammation.
AB  - To identify the active components of honeybee venom in production of inflammation
      and pain-related behaviors, five major peptidergic subfractions were separated,
      purified and identified from the whole honeybee venom. Among them, four active
      peptidergic components were characterized as apamin, mast-cell degranulating
      peptide (MCDP), phospholipase A(2) (PLA(2))-related peptide and melittin,
      respectively. All five subfractions were effective in production of local
      inflammatory responses (paw edema) in rats although the efficacies were
      different. Among the five identified subfractions, only MCDP, PLA(2)-related
      peptide and melittin were able to produce ongoing pain-related behaviors shown as
      paw flinches, while only apamin and melittin were potent to produce both thermal
      and mechanical hypersensitivity. As shown in our previous report, melittin was
      the most potent polypeptide in production of local inflammation as well as
      ongoing pain and hypersensitivity. To further explore the peripheral mechanisms
      underlying melittin-induced nociception and hypersensitivity, a single dose of
      capsazepine, a blocker of thermal nociceptor transient receptor potential
      vanilloid receptor 1, was treated s.c. prior to or after melittin administration.
      The results showed that both pre- and post-treatment of capsazepine could
      significantly prevent and suppress the melittin-induced ongoing nociceptive
      responses and thermal hypersensitivity, but were without influencing mechanical
      hypersensitivity. The present results suggest that the naturally occurring
      peptidergic substances of the whole honeybee venom have various pharmacological
      potencies to produce local inflammation, nociception and pain hypersensitivity in
      mammals, and among the five identified reverse-phase high pressure liquid
      chromatography subfractions (four polypeptides), melittin, a polypeptide
      occupying over 50% of the whole honeybee venom, plays a central role in
      production of local inflammation, nociception and hyperalgesia or allodynia
      following the experimental honeybee's sting. Peripheral transient receptor
      potential vanilloid receptor 1 is likely to be involved in melittin-produced
      ongoing pain and heat hyperalgesia, but not mechanical hyperalgesia, in rats.

PMID- 16446040
TI  - GABA-induced calcium signaling in cultured enteric neurons is reinforced by
      activation of cholinergic pathways.
AB  - GABA is an important inhibitory transmitter in the CNS. In the enteric nervous
      system, however, both excitatory and inhibitory actions have been reported. Here,
      we investigated the effects of GABA on the intracellular Ca2+ concentration of
      guinea-pig myenteric neurons (at 35 degrees C) using Fura-2-AM. Neurons were
      identified by 75 mM K+ depolarization (5 s), which evoked a transient
      intracellular Ca2+ concentration increase. GABA (10 s) induced a dose dependent
      (5 nM-1 microM) transient intracellular Ca2+ concentration rise in the majority
      of neurons (500 nM GABA: 251+/-17 nM, n=232/289). Interestingly, the response to
      5 microM GABA (n=18) lasted several minutes and did not fully recover. GABA
      response amplitudes were significantly (P<0.001) reduced by GABAA and GABAB
      receptor antagonists (10 microM) bicuculline and phaclofen. The GABAA agonist
      isoguvacine (10 microM) and GABAB agonist baclofen (10 microM) induced similar
      responses as 50 nM GABA, while the GABAC agonist cis-4-aminocrotonic acid (CACA)
      (10 microM) only elicited small responses in a minority of neurons. Removal of
      extracellular Ca2+ abolished all responses while depletion of intracellular Ca2+
      stores by thapsigargin (5 microM) did not alter the responses to 500 nM GABA
      (n=13), but reduction of Ca2+ influx through voltage-dependent Ca2+ channels did.
      The nicotinic antagonist hexamethonium (100 microM) also reduced GABA responses
      by almost 70% suggesting that GABA stimulates cholinergic pathways, while the
      purinergic receptor blocker pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid
      (PPADS) and the 5-HT3 receptor blocker ondansetron only had minor effects.
      CONCLUSION: GABA elicits transient intracellular Ca2+ concentration responses in
      the majority of myenteric neurons through activation of GABAA and GABAB receptors
      and much of the response can be attributed to facilitation of ACh release. Thus
      GABA may act mainly as a modulator that sets the state of excitability of the
      enteric nerve network. A concentration of 5 microM GABA, although frequently used
      in pharmacological experiments, seems to cause a detrimental response reminiscent
      of the neurotoxic effects glutamate has in the CNS.

PMID- 16446041
TI  - Characterization of neurons that express preprotachykinin B in the dorsal horn of
      the rat spinal cord.
AB  - Although it is established that neurokinin B is expressed by some neurons in
      laminae I-III of the rat spinal dorsal horn, little is known about the
      proportions of cells in these laminae that express neurokinin B, or whether these
      are excitatory or inhibitory neurons. Neurokinin B is derived from
      preprotachykinin B, and we have used an antibody against preprotachykinin B to
      address these issues. We found that preprotachykinin B-immunoreactive neurons
      were present throughout laminae I-III, constituting 10-11% of the neuronal
      population in laminae I-II, and 4% of that in lamina III. They formed a prominent
      band in the ventral half of lamina II (where they made up 16% of the population)
      and the dorsalmost part of lamina III. The great majority (99%) of
      preprotachykinin B-immunoreactive axonal boutons contained the vesicular
      glutamate transporter 2, while none contained glutamic acid decarboxylase. Since
      most of these boutons are likely to be derived from local preprotachykinin B
      expressing cells, these observations suggest that most of the latter are
      excitatory interneurons. Although 9% of preprotachykinin B-labeled axonal
      varicosities were substance P-immunoreactive, none contained calcitonin gene
      related peptide, which is consistent with reports that neurokinin B is not
      expressed by primary afferent axons. Many of the preprotachykinin B
      immunoreactive cells contained compounds that are present in putative excitatory
      neurons in laminae I-III: calbindin (84%), protein kinase Cgamma (76%) or
      somatostatin (31%). However, there was little or no overlap between
      preprotachykinin B and three other markers associated with excitatory neurons in
      these laminae: the mu opioid receptor MOR-1, the neurokinin 1 receptor and
      neurotensin. These results suggest that neurokinin B is expressed by specific
      populations of excitatory neurons in the superficial dorsal horn. By examining
      expression of Fos protein in response to intraplantar injection of formaldehyde
      we provide evidence that many of the preprotachykinin B cells in lamina I and the
      outer part of lamina II respond to noxious stimulation.

PMID- 16446042
TI  - Acute implantation of an avulsed lumbosacral ventral root into the rat conus
      medullaris promotes neuroprotection and graft reinnervation by autonomic and
      motor neurons.
AB  - Trauma to the conus medullaris and cauda equina may result in autonomic, sensory,
      and motor dysfunctions. We have previously developed a rat model of cauda equina
      injury, where a lumbosacral ventral root avulsion resulted in a progressive and
      parallel death of motoneurons and preganglionic parasympathetic neurons, which
      are important for i.e. bladder control. Here, we report that an acute
      implantation of an avulsed ventral root into the rat conus medullaris protects
      preganglionic parasympathetic neurons and motoneurons from cell death as well as
      promotes axonal regeneration into the implanted root at 6 weeks post
      implantation. Implantation resulted in survival of 44+/-4% of preganglionic
      parasympathetic neurons and 44+/-4% of motoneurons compared with 22% of
      preganglionic parasympathetic neurons and 16% of motoneurons after avulsion
      alone. Retrograde labeling from the implanted root at 6 weeks showed that 53+/
      13% of surviving preganglionic parasympathetic neurons and 64+/-14% of surviving
      motoneurons reinnervated the graft. Implantation prevented injury-induced atrophy
      of preganglionic parasympathetic neurons and reduced atrophy of motoneurons.
      Light and electron microscopic studies of the implanted ventral roots
      demonstrated a large number of both myelinated axons (79+/-13% of the number of
      myelinated axons in corresponding control ventral roots) and unmyelinated axons.
      Although the diameter of myelinated axons in the implanted roots was
      significantly smaller than that of control roots, the degree of myelination was
      appropriate for the axonal size, suggesting normal conduction properties. Our
      results show that preganglionic parasympathetic neurons have the same ability as
      motoneurons to survive and reinnervate implanted roots, a prerequisite for
      successful therapeutic strategies for autonomic control in selected patients with
      acute conus medullaris and cauda equina injuries.

PMID- 16446043
TI  - Working memory and acquisition of implicit knowledge by imagery training, without
      actual task performance.
AB  - This study investigated acquisition of a mirror-reading skill via imagery
      training, without the actual performance of a mirror-reading task. In experiment
      I, healthy volunteers simulated writing on an imaginary, transparent screen
      placed at eye level, which could be read by an experimenter facing the subject.
      Performance of this irrelevant motor task required the subject to imagine the
      letters inverted, as if seen in a mirror from their own point of view (imagery
      training). A second group performed the same imagery training interspersed with a
      complex, secondary spelling and counting task. A third, control, group simply
      wrote the words as they would normally appear from their own point of view. After
      training with 300 words, all subjects were tested in a mirror-reading task using
      60 non-words, constructed according to acceptable letter combinations of the
      Portuguese language. Compared with control subjects, those exposed to imagery
      training, including those who switched between imagery and the complex task,
      exhibited shorter reading times in the mirror-reading task. Experiment II
      employed a 2 x 3 design, including two training conditions (imagery and actual
      mirror-reading) and three competing task conditions (a spelling and counting
      switching task, a visual working memory concurrent task, and no concurrent task).
      Training sessions were interspersed with mirror-reading testing sessions for non
      words, allowing evaluation of the mirror-reading acquisition process during
      training. The subjects exposed to imagery training acquired the mirror-reading
      skill as quickly as those exposed to the actual mirror-reading task. Further,
      performance of concurrent tasks together with actual mirror-reading training
      severely disrupted mirror-reading skill acquisition; this interference effect was
      not seen in subjects exposed to imagery training and performance of the switching
      and the concurrent tasks. These results unequivocally show that acquisition of
      implicit skills by top-down imagery training is at least as efficient as bottom
      up acquisition.

PMID- 16446044
TI  - Incapacitated rape and alcohol use: a prospective analysis.
AB  - This study examined timing of alcohol-related sexual assaults (incapacitated
      rape) in relation to both alcohol consumption and alcohol-related negative
      consequences. The sample was drawn from a randomly selected pool of college
      students across three campuses (n=1238) followed over a three year time period.
      91% of students never experienced an incapacitated rape, 2% reported an
      incapacitated rape prior to the first assessment point (n=30), and 6% reported
      one over the course of the study (n=76). Results indicated that incapacitated
      rape was associated with higher alcohol use and more negative consequences in the
      years prior to the assault. Incapacitated rape was also associated with higher
      alcohol use and more negative consequences during the year in which the rape took
      place and subsequent years, with highest rates measured for the year of the rape.
      These results suggest alcohol use can function as both risk factor and
      consequence of sexual victimization.

PMID- 16446045
TI  - Substance use among emergency room patients: Is self-report preferable to
      biochemical markers?
AB  - AIM OF STUDY: To explore the validity of self-reported substance use among
      emergency room populations and the processes of sample selection bias, to
      establish their influence on the prevalence rates found. METHODS: Self-reported
      alcohol and illicit drug use of patients in the emergency room is compared with
      results from an alcohol breath analyser and urine toxicology. RESULTS: Variations
      in reported substance use occur when comparing self-report measures with alcohol
      breath analyser results and urine toxicology. Self-reported alcohol use was found
      among 7.5% of the patients compared with 4.7% based on alcohol breath analysers.
      Illicit drug use was reported by 9.0% of the patients whereas urine toxicology
      resulted in 30% patients positive for illicit drug use. Patients that voluntarily
      participate in the study differ from those that do not participate. Patients who
      refuse an alcohol breath analyser report slightly more alcohol use prior to the
      injury (difference not significant), and patients who provide a urine sample
      report more illicit drug use prior to the injury compared to those that refuse.
      DISCUSSION: Differences in prevalence rates can be explained partly by the
      measurements used and partly by sample selection bias. Self-reported alcohol use
      and self-reported illicit drug use are preferable to the "gold standard" when
      used among emergency room patients, because both measures provide more accurate
      information on the actual use. Sample selection bias also influences the
      prevalence rates.

PMID- 16446046
TI  - Gender differences in predictors of drinking behavior in adolescents.
AB  - This study explored the differences in the risk factors associated with alcohol
      use, problem drinking, and related consequences between male and female high
      school students in eastern Taiwan. A total of 771 10th grade students, including
      327 boys (42.4%) and 444 girls (57.6%), from four randomly selected high schools
      in eastern Taiwan were included in the survey. Multiple logistic regression
      analyses were performed. In conclusion, paternal drinking was found to be an
      important factor for the development of alcohol use in adolescent boys but had
      less impact on girls when compared with maternal drinking. Peer norms and peer
      relationships had greater effects on drinking behavior in female than in male
      adolescents. Alcohol use appeared to be much more closely related to family
      relationships in female than in male adolescents. In adolescent boys, deviant
      self-image was the real factor causing problem drinking. Therefore, preventive
      intervention for boys should focus on managing psychological distress and
      strengthening positive self-image, while correcting peer drinking norms, learning
      of drinking refusal self-efficacy, establishing friendships without drinking, and
      positive parent-child communication should be enhanced for girls.

PMID- 16446047
TI  - Pathophysiological impact of transcellular metabolism for the induction of
      clinical aspirin resistance.

PMID- 16446048
TI  - Possible role of potassium channel, big K in etiology of schizophrenia.
AB  - Schizophrenia (SZ), a common severe mental disorder, affecting about 1% of the
      world population. However, the etiology of SZ is still largely unknown. It is
      believed that molecules that are in an association with the etiology and
      pathology of SZ are neurotransmitters including dopamine, 5-HT and gamma
      aminobutyric acid (GABA). But several lines of evidences indicate that potassium
      large conductance calcium-activated channel, known as BK channel, is likely to be
      included. BK channel belongs to a group of ion channels that plays an important
      role in regulating neuronal excitability and transmitter releasing. Its
      involvement in SZ emerges as a great interest. For example, commonly used
      neuroleptics, in clinical therapeutic concentrations, alter calcium-activated
      potassium conductance in central neurons. Diazoxide, a potassium channel
      opener/activator, showed a significant superiority over haloperidol alone in the
      treatment of positive and general psychopathology symptoms in SZ. Additionally,
      estrogen, which regulates the activity of BK channel, modulates dopaminergic D2
      receptor and has an antipsychotic-like effect. Therefore, we hypothesize that BK
      channel may play a role in SZ and those agents, which can target either BK
      channel functions or its expression may contribute to the therapeutic actions of
      SZ treatment.

PMID- 16446050
TI  - Are there distinct lymphatic flow patterns in the Breast?

PMID- 16446049
TI  - Stress-induced change of mitochondria membrane potential regulated by genomic and
      non-genomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD.
AB  - Posttraumatic stress disorder (PTSD) is a common psychiatric disorder often
      accompanied by morphologic changes in the hippocampus. Brain imaging studies have
      demonstrated a strong relationship between PTSD and a reduction in the volume of
      the hippocampus; however, the mechanisms that cause such atrophy are not well
      understood. In an attempt to expand our knowledge of these mechanisms, our theory
      has focused on the role of mitochondria in cell death, which may be associated
      with atrophy of the hippocampus. In addition to their function in respiration,
      mitochondria play an important role in the regulation of cytochrome c, an
      apoptotic signaling element. Normally, cytochrome c resides in the intermembrane
      space of mitochondria, where membrane potential exists-negative inside of about
      180-200mV. In response to a variety of apoptotic stimuli, mitochondria membrane
      potential can be changed by genomic and non-genomic cortisol action. For the non
      genomic action, stress increases cortisol levels, which activates the
      glucocorticoid receptor (GR). Stress-activated GR directly binds to mitochondrial
      membranes to regulate membrane potential. The GR will also produce a genomic
      action, in which GR, in interacting with several other molecules (such as heat
      shock proteins 90/70/40, etc.), translocates into the nucleus of the cell, where
      it binds to DNA and exerts transcriptional action. As one of the downstream
      modulaters of GR activation, Bax can be up regulated and translocated to the
      mitochondria, where it binds to modulator of apoptosis-1 (MAP-1), a mitochondrial
      effector of BAX to cause change Deltapsi. These non-genomic and genomic cortisol
      induced changes of the mitochondrial membrane potential can result in the release
      of cytochrome c from the mitochondria to the cytoplasm where the cytochrome c
      promotes of the action of caspases which leads to apoptosis. Therefore, we
      hypothesis that stress-induced changes of mitochondrial membrane potential are
      regulated by non-genomic and genomic actions of cortisol in hippocampal neurons.
      Understanding the molecular mechanism for stress-induced cell death in the
      hippocampus may shed a new light on developing a mitochondrial membrane potential
      related therapeutic drug and/or diagnostic tool for PTSD.

PMID- 16446051
TI  - Stem cell origin theory of the inguinal hernia.

PMID- 16446053
TI  - Therapeutic significance of ectophosphatase inhibitors in reversal of multi-drug
      resistance.

PMID- 16446052
TI  - Use of anti-thrombotic agents during chemotherapy for epithelial ovarian cancer.
AB  - The association between malignancy and venous thrombotic events is well
      established. However, arterial thrombosis among cancer patients is extremely
      rarely reported. There are several mechanisms of arterial thrombosis or embolism
      in malignancy. Important mechanisms in arterial thrombogenesis are shear stress
      induced platelet aggregation and platelet-derived microparticles. Both of these
      are induced by major abdominal surgery. A major abdominopelvic surgery followed
      by adjuvant platinum-based combined chemotherapy is routinely performed for
      epithelial ovarian cancer which is the leading cause of death among all
      gynecologic malignancies. These patients have a greater risk of arterial
      thrombosis at the postoperative period. If the affected arteries are relatively
      larger, clinical findings will be evident due to limb ischemia or fatal organ
      infarctions. However, thrombosis of the small arteries disturbs the tissue
      circulation which is extremely important for the chemotherapeutic agents to reach
      the residual tumor cells. When the thrombosis of small arteries is prevented,
      these drugs will reach all of the residual macroscopic or microscopic tumoral
      tissues and so the prognosis of the patients may be improved. Therefore, we
      hypothesize that anti-platelet therapy with aspirin is needed to be initiated
      during the postoperative period of epithelial ovarian cancer patients and be
      continued as long as chemotherapy goes on. Such an approach might have a role in
      optimizing the oncological prognosis of these patients via increasing the
      effectiveness of cytotoxic therapy since some of the recurrences may be caused by
      some microscopic tumor foci which were not affected by cytotoxic drugs because of
      subclinical small arterial thromboses.

PMID- 16446054
TI  - Preservation of HER2/neu gene during evolution: possible physiological role and
      survival advantages.

PMID- 16446055
TI  - A technique for adaptive image-guided helical tomotherapy for lung cancer.
AB  - PURPOSE: The gross tumor volume (GTV) for many lung cancer patients can decrease
      during the course of radiation therapy. As the tumor reduces in size during
      treatment, the margin added around the GTV effectively becomes larger, which can
      result in the excessive irradiation of normal lung tissue. The specific goal of
      this study is to evaluate the feasibility of using image-guided adaptive
      radiation therapy to adjust the planning target volume weekly based on the
      previous week's CT image sets that were used for image-guided patient setup.
      METHODS AND MATERIALS: Megavoltage computed tomography (MVCT) images of the GTV
      were acquired daily on a helical tomotherapy system. These images were used to
      position the patient and to measure reduction in GTV volume. A planning study was
      conducted to determine the amount of lung-sparing that could have been achieved
      if adaptive therapy had been used. Treatment plans were created in which the
      target volumes were reduced after tumor reduction was measured. RESULTS: A total
      of 158 MVCT imaging sessions were performed on 7 lung patients. The GTV was
      reduced by 60-80% during the course of treatment. The tumor reduction in the
      first 60 days of treatment can be modeled using the second-order polynomial R =
      0.0002t(2) - 0.0219t + 1.0, where R is the percent reduction in GTV, and t is the
      number of elapsed days. Based on these treatment planning studies, the absolute
      volume of ipsilateral lung receiving 20 Gy can be reduced between 17% and 23%
      (21% mean) by adapting the treatment delivery. The benefits of adaptive therapy
      are the greatest for tumor volumes > or =25 cm3 and are directly dependent on GTV
      reduction during treatment. CONCLUSIONS: Megavoltage CT-based image guidance can
      be used to position lung cancer patients daily. This has the potential to
      decrease margins associated with daily setup error. Furthermore, the adaptive
      therapy technique described in this article can decrease the volume of healthy
      lung tissue receiving above 20 Gy. However, further study is needed to determine
      whether adaptive therapy could result in the underdosing of microscopic
      extension.

PMID- 16446056
TI  - Whole-brain radiotherapy with or without efaproxiral for the treatment of brain
      metastases: Determinants of response and its prognostic value for subsequent
      survival.
AB  - PURPOSE: To determine the prognostic factors for radiographic response and its
      prognostic value for subsequent survival in patients undergoing whole-brain
      radiotherapy (WBRT) for brain metastases. METHODS AND MATERIALS: Five hundred
      fifteen eligible patients were randomized in a phase III trial evaluating WBRT
      and supplemental oxygen with or without efaproxiral, an allosteric modifier of
      hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor
      oxygenation, potentially increasing tumor radiosensitivity. Brain images were
      obtained at baseline and at scheduled follow-up visits after WBRT. Landmark
      analysis was used to assess the ability of response at selected time points to
      predict subsequent survival. Logistic regression was used to assess determinants
      of response at 3 months. RESULTS: Treatment arm, Karnofsky Performance Status,
      presence or absence of liver metastases, and primary site were all determinants
      of response at the 3-month follow-up visit, with patients in the efaproxiral arm
      experiencing a 67% greater odds of response at this visit (p = 0.02). Response at
      3 and 6 months was a significant prognostic factor for longer subsequent
      survival. CONCLUSIONS: The 3-month scan is a valuable prognostic factor for
      subsequent survival in patients with brain metastases treated with WBRT. Patients
      in the efaproxiral arm had a higher response rate at 3 and 6 months than those in
      the control arm.

PMID- 16446057
TI  - Cause-specific mortality in long-term survivors of breast cancer: A 25-year
      follow-up study.
AB  - PURPOSE: To assess long-term cause-specific mortality in breast cancer patients.
      PATIENTS AND METHODS: We studied mortality in 7425 patients treated for early
      breast cancer between 1970 and 1986. Follow-up was 94% complete until January
      2000. Treatment-specific mortality was evaluated by calculating standardized
      mortality ratios (SMRs) based on comparison with general population rates and by
      using Cox proportional hazards regression. RESULTS: After a median follow-up of
      13.8 years, 4160 deaths were observed, of which 76% were due to breast cancer.
      Second malignancies showed a slightly increased SMR of 1.2 (95% confidence
      interval [CI], 1.0-1.3). Radiotherapy (RT) as compared with surgery was
      associated with a 1.7-fold (95% CI, 1.2-2.5) increased mortality from
      cardiovascular disease (CVD). After postlumpectomy RT, no increased mortality
      from CVD was observed (hazard ratio, 1.0; 95% CI, 0.5-1.9). Postmastectomy RT
      administered before 1979 and between 1979 and 1986 was associated with a 2-fold
      (95% CI, 1.2-3.4) and 1.5-fold (95% CI, 0.9-2.7) increase, respectively. Patients
      treated before age 45 experienced a higher SMR (2.0) for both solid tumors (95%
      CI, 1.6-2.7) and CVD (95% CI, 1.3-3.1). CONCLUSION: Currently, a large population
      of breast cancer survivors is at increased risk of death from CVDs and second
      cancers, especially when treated with RT at a young age. Patients irradiated
      after 1979 experience low (postmastectomy RT) or no (postlumpectomy RT) excess
      mortality from CVD.

PMID- 16446058
TI  - Prospective multicenter study of combined treatment with chemotherapy and
      radiotherapy in breast cancer women with the rare clinical scenario of
      ipsilateral supraclavicular node recurrence without distant metastases.
AB  - PURPOSE: To evaluate the role of chemotherapy combined with curative radiotherapy
      in breast cancer patients who presented with recurrent ipsilateral
      supraclavicular lymph node metastases (ISLM) without "nonregional disease," we
      designed an observational study performed prospectively. PATIENTS AND METHODS:
      Forty-four consecutive patients with ISLM from breast cancer as part of recurrent
      regional disease without distant metastases were included in this study. All
      patients received chemotherapy with doxorubicin-based schema or paclitaxel for
      six courses and curative radiotherapy (60 Gy/30 fractions of 2 Gy/5 days a week).
      An "involved field" radiation was delivered during the interval between the third
      and fourth chemotherapy course; hormonal therapy was given based on receptor
      status. RESULTS: The rate of overall clinical response after chemotherapy and
      radiotherapy was 94.9%. Median time to progression and overall survival were 28
      and 40 months, respectively; the 5-year actuarial overall survival and disease
      free survival rates were 35% (95% confidence interval, 19-51) and 20% (95%
      confidence interval, 6-34), respectively. CONCLUSION: A curative course of
      intravenous chemotherapy and radical irradiation is feasible in patients with
      ISLM. All patients presenting recurrence in supraclavicular nodes should be
      treated with definitive locoregional treatments and systemic therapy because the
      outcomes are better than might be historically assumed.

PMID- 16446059
TI  - Transposon-derived repeats in the human genome and 5-methylcytosine-associated
      mutations in adjacent genes.
AB  - Transposon-derived repeats (TDR) represent approximately 50% of the human genome.
      A transposon suppression system has been proposed to explain why transposon
      derived repeats (TDR) seldom cause mutations in humans. If this system is based
      on DNA methylation, a correlation might exist between amount of TDR adjacent to
      genes and frequency of coding sequence mutations due to m5C deaminations. To test
      this hypothesis we selected 385 genes based on availability of accurate
      information on their genome structure and mutation patterns (at least 10
      mutations described in the Human Gene Mutation Database (HGMD)). The CENSOR
      program was used to estimate amount and class of TDR for the gene region and an
      arbitrarily selected 1 KB from each end. We assumed all C --> T transitions to be
      possible 5-methylcytosine-associated mutations (MAM) and calculated the number
      and proportion of MAM in the 385 genes. If there is a strong correlation between
      methylation of certain CpX dinuclecotides and TDR we might be able to detect it
      despite limitations of available data for this analysis. We found statistically
      significant correlations between: i) TDR and number of MAM in genes (r = 0.118, p
      = 0.02), ii) SINE-TDR and proportion of CpG --> TpG (r = 0.11, p = 0.03); limited
      to MIR elements only (r = 0.14, p = 0.006), and iii) LINE-TDR and proportion of
      CpT --> TpT (r = 0.166, p = 0.04). The group of genes with no TDR had a
      statistically significant lower proportion of MAM (184/479, 0.38 vs. 6466/14524,
      0.46; p = 0.009) with differences noted for CpA --> TpA (35/479, 0.073 vs.
      1380/11474; p = 0.003). In addition, CpT --> TpT were least common in genes with
      no TDR (8/479, 0.017), intermediate in genes with TDR in genomic sequence but not
      mRNA (337/11474, 0.029) and most common in genes with TDR within mature mRNA
      (121/3050, 0.040; p for trend = 0.003). Our data suggest that TDR adjacent to
      genes may sometimes influence methylation of cytosines in coding sequences to a
      degree that it affects mutation patterns. These observations should be followed
      up with further database analysis and biochemical studies.

PMID- 16446060
TI  - Bid, a BH3-only multi-functional molecule, is at the cross road of life and
      death.
AB  - Bid, BH3-interacting domain death agonist, was initially cloned based in its
      ability to interact with both Bcl-2 and Bax. Bid contains only the BH3 domain,
      which is required for its interaction with the Bcl-2 family proteins and for its
      pro-death activity. Bid is susceptible to proteolytic cleavage by caspases,
      calpains, Granzyme B and cathepsins. Bid is important to cell death mediated by
      these proteases and thus is the sentinel to protease-mediated death signals.
      Protease-cleaved Bid is able to induce multiple mitochondrial dysfunctions,
      including the release of the inter-membrane space proteins, cristae
      reorganization, depolarization, permeability transition and generation of
      reactive oxygen species. Thus Bid is the molecular linker bridging various
      peripheral death pathways to the central mitochondria pathway. Recent studies
      further indicate that Bid may be more than just a killer molecule. Deletion of
      Bid inhibits carcinogenesis in the liver, although this genetic alteration
      promotes tumorigenesis in the myeloid cells. This is likely related to the
      function of Bid to promote cell cycle progression into S phase. Bid could be also
      involved in the maintenance of genomic stability by engaging at mitosis
      checkpoint. These novel findings indicate that this BH3-only Bcl-2 family protein
      has a diverse array of functions that are important to both the life and death of
      the cell.

PMID- 16446061
TI  - Presence of antibodies to non-structural proteins of foot-and-mouth disease virus
      in repeatedly vaccinated cattle.
AB  - For the purpose of removing infected animals by detecting humoral immune
      responses to non-structural proteins of the foot-and-mouth disease (FMD) virus,
      antibodies induced by contaminated residual non-structural proteins contained in
      less pure FMD vaccine can be problematic for serological screening. The aim of
      the present study was to measure the possible presence of antibodies against
      these non-structural proteins in repeatedly vaccinated calves and beef cattle.
      Five imported FMD vaccines were examined using two commercial ELISA kits, UBI
      FMDV NS EIA and Ceditest FMDV-NS, for serological testing. After five doses of
      vaccination, the serum of one calf tested positive, and two vaccines induced a
      significant increase in anti-3ABC antibodies in calves. This finding demonstrated
      that a positive reaction to non-structural proteins due to impurities in the FMD
      vaccine was detectable using commercial tests. A low percentage of field sera
      sampled from beef cattle in Kinmen also tested positive, but the key factor
      resulting in the positive reactions could not be positively identified based on
      our data.

PMID- 16446063
TI  - Study of the critical points of HPMC hydrophilic matrices for controlled drug
      delivery.
AB  - The knowledge of the percolation thresholds of a system results in a clear
      improvement of the design of controlled release dosage forms such as inert
      matrices. Despite hydrophilic matrices are one of the most used controlled
      delivery systems in the world, but actuality, the mechanisms of drug release from
      these systems continue to be a matter of debate nowadays. The objective of the
      present paper is to apply the percolation theory to study the release and
      hydration rate of hydrophilic matrices. Matrix tablets have been prepared using
      KCl as a drug model and HPMC K4M as matrix-forming material, employing five
      different excipient/drug particle size ratios (ranging from 0.42 to 2.33). The
      formulations studied containing a drug loading in the range of 20-90% (w/w).
      Dissolution studies were carried out using the paddle method and the water uptake
      measurements were performed using a modified Enslin apparatus. In order to
      estimate the percolation threshold, the behaviour of the kinetic parameters with
      respect to the volumetric fraction of each component at time zero, was studied.
      The percolation theory has been applied for the first time to the study of matrix
      type controlled delivery systems. The application of this theory allowed to
      explain changes in the release and hydration kinetics of these matrices. The
      critical points observed in dissolution and water uptake studies can be
      attributed to the excipient percolation threshold, being this threshold one of
      the main factors governing the gel layer formation and consequently, the drug
      release control from hydrophilic matrices.

PMID- 16446062
TI  - The effect of oestrogen on cytokine and antioxidant levels in male to female
      transsexual patients.
AB  - OBJECTIVE: Whilst hormone replacement therapy (HRT) can be beneficial, it can be
      associated with deep venous thrombosis (DVT) and stroke. As male to female
      transsexuals take much higher doses of oestrogen than women on HRT, they provide
      a unique opportunity to study the long-term effects of oestrogen in a group of
      relatively young individuals who are largely free of established vascular
      disease. METHODS: Thirty-eight male to female gender patients were enrolled into
      the study. Of these, 25 were receiving oestrogen treatment and 13 who were not on
      treatment served as a control group. Serum levels of cholesterol, HDL,
      triglycerides, Interleukin 6 (IL-6), nitric oxide (NO), glutathione, and
      superoxide dismutase (SOD) were measured in all patients. RESULTS: The results
      showed that compared to the control group, patients on oestrogen had
      significantly raised levels of NO (32.1+/-14.3 versus 20.3+/-10.0, P<0.05) and
      reduced levels of IL-6 (0.75+/-0.6 versus 1.37+/-0.7, P<0.05) and SOD (13.2+/-3.0
      versus 24.0+/-10.0, P<0.05). These changes were not accompanied by any
      significant change in plasma lipid levels. CONCLUSION: It would appear that the
      very high levels of oestrogen taken by the gender patients produce similar
      beneficial effects to those seen in women on HRT. However, in this patient group
      it appears that these changes are independent of changes in cholesterol,
      triglyceride, and HLD.

PMID- 16446064
TI  - A fibrin encapsulated liposomes-in-chitosan matrix (FLCM) for delivering water
      soluble drugs. Influences of the surface properties of liposomes and the
      crosslinked fibrin network.
AB  - A depot drug delivery system, fibrin encapsulated liposome-in-chitosan matrix
      (FLCM), has been developed to deliver a water-soluble drug which is configured by
      a porous chitosan matrix containing a bovine fibrin network encapsulated
      different surface properties of liposomes. Quinacrine (QR), a water-soluble, low
      molecular weight fluorescent marker, is used as a model drug to evaluate the
      delivery characteristics of the system. The SEM photographs show that the fibrin
      network adheres to the surfaces and pores of the chitosan matrix of a FLCM
      system. The QR release periods of the FLCM are sustained for about four times
      longer than those of QR encapsulated into the liposomes. However, the QR release
      periods and profiles of the FLCM are influenced by the surface properties of
      liposomes. The release of QR from FLCM is sustained for 9 days for neutral
      liposomes and only 5 days for PEG modified liposomes (PEG-liposome). After
      crosslinking the fibrin network of the FLCM with 0.5% of glutaldehyde, the
      release of QR is further sustained for 17 days with good linear profiles (e.g.,
      13 days) and with 50% of reduced burst release compared with those of without
      crosslinking, indicating that the stability of the fibrin network plays an
      important role on QR release of the system. More interestingly, the release
      periods and profiles of QR of the FLCM system are highly similar to those of
      Tirofiban, low-molecular weight of a water-soluble clinical cardiovascular drug,
      although the study has been done by human platelet poor plasma instead of bovine
      fibrinogen as a source of fibrin network. It suggests that the QR is a suitable
      model for investigating the drug delivery behaviors for water-soluble, low
      molecular weight drugs of the FLCM. In conclusion, with QR as a model drug, FLCM
      with crosslinked fibrin network can effectively sustain the release of QR for 17
      days but the release profiles are influenced by the surface properties of
      encapsulated liposomes. This study suggests that FLCM may have the potential as a
      depot drug delivery system for water-soluble drugs.

PMID- 16446065
TI  - CNS activity of Calotropis gigantea roots.
AB  - Alcoholic extract of peeled roots of Calotropis gigantea R.Br. (Asclepiadaceae)
      was tested orally in albino rats at the dose level of 250 and 500 mg/kg
      bodyweight for CNS activity. Prominent analgesic activity was observed in Eddy's
      hot plate method and acetic acid induced writhings. The paw licking time was
      delayed and the numbers of writhings were greatly reduced. Significant
      anticonvulsant activity was seen as there was a delay in the onset of
      pentylenetetrazole induced convulsions as well as decrease in its severity. The
      extract treated rats spent more time in the open arm of EPM showing its
      antianxiety activity. There was a decrease in the locomotor activity. The fall
      off time (motor coordination) was also decreased. A potentiation in the
      pentobarbitone-induced sleep due to the sedative effect of the extract was
      observed. No mortality was seen upto the dose of 1 g/kg. These results show the
      analgesic, anticonvulsant, anxiolytic and sedative effect of the extract.

PMID- 16446066
TI  - In vivo efficacy of different extracts of Edelweiss (Leontopodium alpinum Cass.)
      in animal models.
AB  - Dichloromethane, methanolic and CO(2) extracts of the aerial parts and roots of
      Edelweiss (Leontopodium alpinum Cass.) were investigated for their anti
      inflammatory and analgesic effects after oral administration. The highest
      activity in rat's paw edema assay was found for the lipophilic extracts of the
      aerial plant parts (dose 200 mg/kg), exhibiting a swelling reduction of 72%
      (CO(2)-extract) and 80% (DCM-extract), respectively. Histological evaluation of
      the treated paws showed a significant reduction of the inflammatory response in
      the pre-treated specimens. On the contrary in the acetic acid-induced writhing
      test the dichloromethane extract of the root extract exhibited more pronounced
      analgesic effects than the extracts of the aerial parts, suggesting a different
      pattern of active compounds. As far as gastrointestinal effects are concerned,
      oral administration of aerial parts (hDCM 200 mg/kg) to mice induces a highly
      significant inhibition in gastrointestinal propulsion probably related to the
      presence of so far unknown compounds. Moreover, the antioxidant capacity of some
      extracts was studied in order to establish a possible correlation with anti
      inflammatory properties.

PMID- 16446067
TI  - Inhibition of morphine tolerance by processed Aconiti tuber is mediated by kappa
      opioid receptors.
AB  - Previously, we found that processed Aconiti tuber (PAT) could inhibit morphine
      tolerance in mice. In the present study, we investigated mechanisms underlying
      this effect. Mice received subcutaneous (s.c.) morphine (10 mg/kg) and oral PAT
      at a subanalgesic dose (0.3 g/kg), once a day for 12 days. Additional PAT-treated
      groups received morphine and PAT, at 120 min after pretreatment with s.c.
      clocinnamox mesylate (C-CAM) (0.5 mg/kg), or nor-binaltorphimine (nor-BNI) (5
      mg/kg). The antinociceptive effect was assessed with the tail pressure test, at
      60 min after the daily s.c. morphine injections were given. In the placebo
      treated group, repeated morphine injections caused morphine tolerance, and
      morphine antinociception was abolished by day 6, whereas in PAT-treated groups,
      significant antinociception was maintained until day 12, suggesting that PAT
      inhibited morphine tolerance, thereby sustaining morphine antinociception. C-CAM,
      a selective mu-opioid receptor (MOR) antagonist, blocked morphine antinociception
      whereas nor-BNI, a selective kappa-opioid receptor (KOR) antagonist, did not.
      However, both C-CAM and nor-BNI could block the antinociception maintained by the
      morphine-PAT combination. Results of the study suggested that chronic treatment
      with PAT at a subanalgesic dose maintained MOR-mediated morphine antinociception
      by attenuating development of morphine tolerance, and that this tolerance
      attenuating effect of PAT was mediated by KOR.

PMID- 16446069
TI  - Therapeutic experience of recurrent myoepithelial carcinoma by superselective
      intra-arterial chemotherapy infused high-dose CDDP.
AB  - Myoepithelial carcinoma is one of several new entities added to the updated
      classification of salivary gland tumors by the WHO in 1991. This tumor most
      frequently occurs in parotid gland. This is the first report presenting the tumor
      in floor of the mouth. It is a rare and prognostic poor cancer. Especially, there
      was not good therapy for recurrent cases. We treated the patient with repeated
      recurrences three times and presented in bilateral parapharyngeal space to
      skullbase in this time. We targeted function preservation and complete cure. In
      order to accomplish the both objections he received the superselective intra
      arterial chemotherapy infused high-dose CDDP with radiation. We confirmed tumor
      free in FDG-PET in 2 months after the treatment. Now, we cannot detect any
      recurrence in 7 months after the treatment and he can eat anything and
      communicate anybody as before treated. We should follow-up him carefully.

PMID- 16446071
TI  - Acute myocardial ischemia after aortic valve replacement: a comprehensive
      diagnostic evaluation using dynamic multislice spiral computed tomography.
AB  - We describe the case of a 72-year-old man presenting with endocarditis and
      clinical signs of acute myocardial ischemia after biological aortic valve
      replacement. A comprehensive cardiac dynamic multislice spiral computed
      tomography demonstrated: (1) an endocarditic vegetation of the aortic valve; (2)
      a subvalvular leakage feeding a paravalvular pseudoaneurysm based on an aortic
      root abscess with subsequent compromise of the systolic blood flow in the left
      main coronary artery and the resulting myocardial perfusion deficit.

PMID- 16446072
TI  - Coronary artery bypass graft (CABG) patency: assessment with high-resolution
      submillimeter 16-slice multidetector-row computed tomography (MDCT) versus
      coronary angiography.
AB  - PURPOSE: To investigate the ability of 16-slice multidetector-row computed
      tomography (MDCT) to visualize coronary artery bypass graft (CABG) patency and to
      detect bypass stenoses. MATERIALS AND METHODS: Thirty-two patients with 94 grafts
      (20 mammary artery grafts, 74 venous grafts) were investigated by 16-slice MDCT
      using a scan protocol with 12 x 0.75 mm slice collimation (pitch 0.3), 420 ms
      rotation time and simultaneous electrocardiogram (ECG)-registration. One hundred
      milliliters iodinated contrast agent were injected with a delay according to the
      individually determined contrast agent transit time. Patients with heart rates
      above 60 bpm received oral beta-blockade. Cross-sectional images with a slice
      width of 1.0 mm (0.5 mm increment) were reconstructed using an ECG-gated half
      scan reconstruction or a multisegment reconstruction algorithm depending on the
      heart rate. Bypass grafts were evaluated concerning patency and presence of
      stenoses > or = 50% diameter reduction on cross-sectional images, multiplanar
      reformations and maximum intensity projections by two independent observers.
      Results were compared to coronary bypass angiography. RESULTS: Sixteen-slice MDCT
      results were compared to those of invasive coronary angiography concerning
      absence or presence of bypass graft occlusion or relevant stenosis > or = 50%
      lumen reduction. Coronary CT angiography (CTA) permitted detection of bypass
      occlusion with 100% sensitivity (28/28) and 98% specificity (64/65). Seventy
      eight percent (observer 1) and 84% (observer 2) of all patent grafts were found
      to be evaluable concerning presence or absence of stenosis. In 34 of 40 (observer
      1) and 38 of 43 (observer 2) bypass grafts, high-grade stenoses were correctly
      ruled out (specificity 85% versus 88%, sensitivity 80% and 82%). Yet, if all
      patients with either unevaluable grafts/graft anastomosis or relevant graft
      stenosis were excluded, only 8/32 patients (25%) had fully diagnostic "negative"
      graft-CTA. According to Kappa statistics, agreement between the observers was 1.0
      and 0.93 concerning occlusion and relevant stenosis, respectively. CONCLUSION:
      Sixteen-slice coronary CTA with sub-millimeter spatial resolution and
      premedication with oral beta-blockade permits non-invasive assessment of coronary
      artery bypass grafts with decreasing numbers of unevaluable graft segments.
      However, patient-based analysis reveals that only a relatively small number of
      patients ("negative" and completely evaluable graft-CTA) truly profits from
      noninvasive work-up and could be spared invasive angiography.

PMID- 16446070
TI  - Sarcopenia in the Caenorhabditis elegans pharynx correlates with muscle
      contraction rate over lifespan.
AB  - In muscles, sarcopenia, the loss of muscle mass, is the major cause of aging
      related functional decline and frailty. Several factors are correlated with
      sarcopenia during aging, including contraction-related cellular injury, oxidative
      stress, endocrine changes and reduced regenerative potential. However the
      involvement of these factors has not been experimentally investigated. Here, we
      report that contraction-related injury may significantly promote the progression
      of sarcopenia in the pharynx of the nematode, Caenorhabditis elegans, a model of
      aging in non-regenerative tissues. Both functional and structural declines in the
      pharynx during aging were significantly delayed in mutants with reduced muscle
      contraction rates. We also examined the role of bacteria in pharynx muscle
      decline during aging, as previous studies reported that antimicrobial treatments
      could extend C. elegans lifespan. Although microbial infection may have enhanced
      functional decline in the pharynx during aging, it was not the sole cause of
      decreased pumping rates in old animals. This study identifies contraction-related
      injury as a factor affecting the initiation and progression of sarcopenia during
      aging. Further, characterization of the specific types of damage induced by
      muscle contraction will be helpful for understanding the underlying causes of
      sarcopenia.

PMID- 16446074
TI  - Nuclear receptor and target gene mRNA abundance in duodenum and colon of dogs
      with chronic enteropathies.
AB  - Nuclear receptors (NR), such as constitutive androstane receptor (CAR), pregnane
      X receptor (PXR) and peroxisome proliferator-associated receptors alpha and gamma
      (PPARalpha, PPARgamma) are mediators of inflammation and may be involved in
      inflammatory bowel disease (IBD) and food responsive diarrhea (FRD) of dogs. The
      present study compared mRNA abundance of NR and NR target genes [multi drug
      resistance gene-1 (MDR1), multiple drug-resistance-associated proteins (MRD2,
      MRD3), cytochrome P450 (CYP3A12), phenol-sulfating phenol sulfotransferase
      (SULT1A1) and glutathione-S-transferase (GST A3-3)] in biopsies obtained from
      duodenum and colon of dogs with IBD and FRD and healthy control dogs (CON; n=7
      per group). Upon first presentation of dogs, mRNA levels of PPARalpha, PPARgamma,
      CAR, PXR and RXRalpha in duodenum as well as PPARgamma, CAR, PXR and RXRalpha in
      colon were not different among groups (P>0.10). Although mRNA abundance of
      PPARalpha in colon of dogs with FRD was similar in both IBD and CON (P>0.10),
      PPARalpha mRNA abundance was higher in IBD than CON (P<0.05). Levels of mRNA of
      MDR1 in duodenum were higher in FRD than IBD (P<0.05) or CON (P<0.001). Compared
      with CON, abundances of mRNA for MRP2, CYP3A12 and SULT1A1 were higher in both
      FRD and IBD than CON (P<0.05). Differences in mRNA levels of PPARalpha and MRP2
      in colon and MDR1, MRP2, CYP3A12 and SULT1A1 in duodenum may be indicative for
      enteropathy in FRD and (or) IBD dogs relative to healthy dogs. More importantly,
      increased expression of MDR1 in FRD relative to IBD in duodenum may be a useful
      diagnostic marker to distinguish dogs with FRD from dogs with IBD.

PMID- 16446073
TI  - Expression cloning screen for modifiers of amyloid precursor protein shedding.
AB  - Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory
      step in the generation of the amyloid beta peptide (Abeta), which is thought to
      provoke the pathogenesis of Alzheimer's disease. To better understand the
      cellular processes that regulate ectodomain shedding of APP we used human
      embryonic kidney 293 cells and applied a sib-selection expression cloning
      approach. In addition to a known activator of APP shedding -- protein kinase A --
      the following cDNAs were identified: the endocytic proteins endophilin A1 and A3,
      the metabotropic glutamate receptor 3 (mGluR3), palmitoyl-protein thioesterase 1
      (PPT1), Numb-like and the kinase MEKK2. Endophilins A1 and A3, as well as mGluR3
      activated APP shedding relatively specifically. They had little or no effect on
      the shedding of the unrelated membrane proteins TNF receptor 2 and P-selectin
      glycoprotein ligand-1. In contrast, MEKK2 and PKA also increased shedding of TNF
      receptor 2, suggesting that these kinases contribute to a general program
      regulating ectodomain shedding. The strongest activator of APP shedding,
      endophilin A3, reduced the rate of APP endocytosis and specifically increased APP
      shedding by the protease alpha-secretase, as measured in an antibody uptake assay
      and by immunoblot analysis. This suggests that endophilin A3 is a novel modulator
      of APP trafficking affecting access of APP to alpha-secretase. In summary, this
      study shows that expression cloning is a suitable way to identify proteins
      controlling ectodomain shedding of membrane proteins.

PMID- 16446075
TI  - In vitro effect of zinc and cadmium on acetylcholinesterase and ectonucleotidase
      activities in zebrafish (Danio rerio) brain.
AB  - Zinc and cadmium are environmental contaminants that induce a wide range of
      effects on CNS. Here we tested the in vitro effect of these metals on
      acetylcholinesterase (AChE) and ectonucleotidase (NTPDase and ecto-5'
      nucleotidase) activities in zebrafish brain. Both zinc and cadmium treatments did
      not alter significantly the zebrafish brain AChE activity. ATP hydrolysis
      presented a significant increase at 1 mM zinc (17%) and the AMPase activity had a
      dose-dependent increase at 0.5 and 1 mM zinc exposure (188% and 199%). After
      cadmium treatment, ATPase activity was significantly increased (53% and 48%) at
      0.5 and 1 mM, respectively. Cadmium, in the range 0.25-1 mM, inhibited ADP
      hydrolysis in a dose-dependent manner (13.4-69%). Ecto-5'-nucleotidase activity
      was only inhibited (38%) in the presence of 1 mM cadmium. It is possible to
      suggest that changes on NTPDase and ecto-5'-nucleotidase activities can be an
      important mechanism involved in neurotoxic effects promoted by zinc and cadmium.

PMID- 16446076
TI  - U18666A-mediated apoptosis in cultured murine cortical neurons: role of caspases,
      calpains and kinases.
AB  - Studies have suggested that cholesterol imbalance in the brain might be related
      to the development of neurological disorders such as Alzheimer's disease and
      Niemann-Pick disease type C. Previously, we have reported that U18666A, a
      cholesterol transport-inhibiting agent, leads to apoptosis and intracellular
      cholesterol accumulation in primary cortical neurons. In this study, we examined
      the effects of U18666A-mediated neuronal apoptosis, and found that chronic
      exposure to U18666A led to the activation of caspases and calpains and
      hyperphosphorylation of tau. Tau hyperphosphorylation is regulated by several
      kinases that phosphorylate specific sites of tau in vitro. Surprisingly, the
      kinase activity of cyclin-dependent kinase 5 decreased in U18666A-treated
      cortical neurons whereas its protein level remained unchanged. The amount of
      glycogen synthase kinase 3 and mitogen-activated protein kinases were found to
      decrease in their phosphorylated states by Western blot analysis. Gene
      transcription was further studied using microarray analysis. Genes encoding for
      kinases and phosphatases were differentially expressed with most up-regulated and
      some down-regulated in expression upon U18666A treatment. The activation of
      cysteine proteases and cholesterol accumulation with tauopathies may provide
      clues to the cellular mechanism of the inhibition of cholesterol transport
      mediated cell death in neurodegenerative diseases.

PMID- 16446077
TI  - Preparation and characterization of liposomes-in-alginate (LIA) for protein
      delivery system.
AB  - This paper describes the preparation and characterization of a novel drug
      delivery system for protein, liposomes-in-alginate (LIA) of biodegradable
      polymers, which is conceived from a combination of the polymer and the lipid
      based delivery systems. LIA were prepared by first entrapping bovine serum
      albumin (BSA), a model protein within multivesicular liposomes (MVLs) by double
      emulsification process, which are then encapsulated within alginate hydrogel
      microcapsule, with untrapped BSA which are added during preparation of MVLs.
      Factors impacting encapsulation efficiency of MVLs are investigated and release
      of protein from the microcapsules in vitro is studied. At the same time,
      characterization of MVLs, microcapsules encapsulated protein formulation and
      integrality analyse of BSA in microcapsules are also studied, with the aim of
      improving the entrapment efficiency and prolonging release time. It is found that
      encapsulation efficiency and size of MVLs are affected by the composition and
      fabrication parameters of LIA. The data also show LIA have high encapsulation
      efficiency (up to 95%), little chemical change in drug caused by the formulation
      process, narrow particle size distribution and spherical particle morphology.
      Drug release assays conducted in vitro indicates that these formulations provide
      sustained release of encapsulated drug over a period, about 2 weeks.

PMID- 16446078
TI  - Glial cells in synaptic plasticity.
AB  - Plasticity of synaptic transmission is believed to be the cellular basis for
      learning and memory, and depends upon different pre- and post-synaptic neuronal
      mechanisms. Recently, however, an increasing number of studies have implicated a
      third element in plasticity; the perisynaptic glial cell. Originally glial cells
      were thought to be important for metabolic maintenance and support of the nervous
      system. However, work in the past decade has clearly demonstrated active
      involvement of glia in stability and overall nervous system function as well as
      synaptic plasticity. Through specific modulation of glial cell function, a wide
      variety of roles for glia in synaptic plasticity have been uncovered.
      Furthermore, interesting circumstantial evidence suggests a glial involvement in
      multiple other types of plasticity. We will discuss recent advances in neuron
      glial interactions that take place during synaptic plasticity and explore
      different plasticity phenomena in which glial cells may be involved.

PMID- 16446079
TI  - Troglitazone induction of COX-2 expression is dependent on ERK activation in
      keratinocytes.
AB  - Cyclooxygenase-2 (COX-2) plays an important role in tumorigenesis of several
      tissues, including skin. We report here that troglitazone, a thiazolidinedione
      class of antidiabetic drug, induced COX-2 expression at both the protein and mRNA
      levels and increased production of prostaglandin E2 (PGE2) in cultured
      keratinocytes. Troglitazone-induced COX-2 expression in keratinocytes was likely
      peroxisome proliferator-activated receptor gamma (PPARgamma)-independent.
      Troglitazone treatment of these cells also resulted in a sustained increase in
      phosphorylation of ERK. We show that induction of COX-2 by troglitazone was
      almost completely inhibited by specific inhibitors of ERK activation. These data
      suggest that troglitazone is capable of inducing COX-2 expression through an ERK
      dependent mechanism in mouse skin keratinocytes.

PMID- 16446080
TI  - Humidity influences exercise capacity in subjects with exercise-induced
      bronchoconstriction (EIB).
AB  - RATIONALE: Exercise-induced bronchoconstriction (EIB) increases in cold and dry
      air and decreases in humid air in subjects with asthma. Few reports have reported
      on the effect of humid environment upon exercise capacity in subjects with EIB.
      OBJECTIVE: The primary aim of the present study was to examine the effect of
      changing the humidity of the environmental air upon exercise capacity measured by
      peak oxygen uptake (V O2 peak), peak ventilation (V Epeak) and peak running speed
      (V peak) and secondarily to assess the influence of environmental humidity upon
      EIB in subjects suffering from EIB. METHODS: Twenty subjects (10-45 years old,
      male/female:13/7) with diagnosed EIB performed exercise testing under
      standardised, regular environmental conditions, 20.2 degrees C (+/- 1.1) and 40%
      (+/- 3.3) relative humidity [mean (+/- SD)], and under standardised humid
      environmental conditions; 19.9 degrees C (+/- 1.0) and 95% (+/- 1.7) relative
      humidity in random order on separate days. Lung function was measured before and
      1, 3, 6, 10 and 15 min after exercise. Heart rate (HR), oxygen uptake (V O2),
      respiratory gas exchange ratio (RER), breathing frequency (BF) and minute
      ventilation (V E) were measured during exercise. RESULTS: V O2 peak and V peak
      increased significantly from 40% to 95% relative humidity of the environmental
      air, 4.5% and 5.9%, respectively (P = 0.001). HRpeak increased significantly in
      the humid environment, while BF(peak) decreased significantly. RERpeak and V
      Epeak did not change significantly. Post-exercise reduction in FEV1 (DeltaFEV1)
      and FEF50 (forced expiratory flow at 50% of FVC) (DeltaFEF50) significantly
      decreased after exercise in a humid environment as compared to regular
      conditions, DeltaFEV1: 12% (7,17) vs. 24% (19,29) [mean (95% confidence
      intervals)], respectively, DeltaFEF50: 20% (12,29) vs. 38% (30,46), respectively
      (P < 0.001). CONCLUSION: Exercise capacity (V O2 peak and V peak) markedly
      improved during exercise in humid air in subjects with EIB, whereas EIB was
      reduced to the half.

PMID- 16446081
TI  - 12-year change in prevalence of respiratory symptoms in elderly Chinese living in
      Hong Kong.
AB  - Respiratory diseases may cause considerable disability in the elderly because of
      their limited respiratory reserve related to aging. This study aimed to assess
      the time trend of respiratory symptoms and common chronic respiratory diseases in
      the elderly Chinese living in Hong Kong. Two questionnaire surveys were conducted
      in 1991-1992 and 2003-2004. Subjects aged > or = 70 years were invited to
      complete a respiratory questionnaire. A total of 2032 (999 male) and 1524 (698
      male) subjects completed the questionnaire surveys in 1991 and 2003,
      respectively. The response rates were 60% in 1991 and 78% in 2003. The prevalence
      of most respiratory symptoms increased over time after adjusting the data for
      age, sex, social status and smoking habits. Comparing the symptoms between 1991
      and 2003, wheeze over the past 12 months increased from 7.5 to 12.1% (adjusted OR
      2.00, 95% CI 1.54-2.61) and morning chest tightness from 4.2 to 8.8% (adjusted OR
      2.48, 95% CI 1.79-3.43). The prevalence of self-reported physician-diagnosed
      emphysema increased over time (2.4-3.1%, adjusted OR 1.78, 95% CI 1.12-2.86), but
      there was no change for asthma (5.1% in 1991 and 5.8% in 2003) or chronic
      bronchitis (6.7% in 1991 and 7.7% in 2003). The prevalence of respiratory
      symptoms has increased over the past 12 years and this may be related to
      environmental factors especially increasing air pollution in Hong Kong.

PMID- 16446083
TI  - Chemical and mineralogical evaluation of slag products derived from the
      pyrolysis/melting treatment of MSW.
AB  - This paper provides the results of studies on the characteristics of novel
      material derived from pyrolysis/melting treatment of municipal solid waste in
      Japan. Slag products from pyrolysis/melting plants were sampled for the purpose
      of detailed phase analysis and characterization of heavy metal-containing phases
      using optical microscopy, electron probe microanalysis (EPMA), XRF and XRD. The
      study revealed that the slag material contains glass (over 95%), oxide and
      silicate minerals (spinel, melilite, pseudowollastonite), as well as individual
      metallic inclusions as the major constituents. A distinct chemical diversity was
      discovered in the interstitial glass in terms of silica content defined as low
      and high silica glass end members. Elevated concentrations of Zn, Cr, Cu, Pb and
      Ba were recorded in the bulk composition. Cu, Pb and Ba behave as incompatible
      elements since they have been markedly characterized as part of polymetallic
      alloys and insignificantly sulfides in the form of spherical metallic inclusions
      associated with tracer amounts of other elements such as Sb, Sn, Ni, Zn, Al, P
      and Si. In contrast, an appreciable amount of Zn is retained by zinc-rich end
      members of spinel and partially by melilite and silica glass. Chromium exhibits
      similar behavior, and is considerably held by Cr-rich spinel. The intense
      incorporation of Zn and Cr into spinel indicates the very effective enrichment of
      these two elements into phases more environmentally resistant than glass. There
      was no evidence, however, that Cu and Pb enter into the structure of the
      crystalline silicates or oxides that may lead to their easier leachability upon
      exposure to the environment.

PMID- 16446082
TI  - Induction of enhanced methane oxidation in compost: temperature and moisture
      response.
AB  - Landfilling is one of the most common ways of municipal solid waste disposal.
      Degradation of organic waste produces CH(4) and other landfill gases that
      significantly contribute to global warming. However, before entering the
      atmosphere, part of the produced CH(4) can be oxidised while passing through the
      landfill cover. In the present study, the oxidation rate of CH(4) was studied
      with various types of compost as possible landfill cover. The influence of
      incubation time, moisture content and temperature on the CH(4) oxidation capacity
      of different types of compost was examined. It was observed that the influence of
      moisture content and temperature on methane oxidation is time-dependent. Maximum
      oxidation rates were observed at moisture contents ranging from 45% to 110% (dry
      weight basis), while the optimum temperature ranged from 15 to 30 degrees C.

PMID- 16446084
TI  - Intraoperative sentinel lymph node examination by frozen section,
      immunohistochemistry and imprint cytology during breast surgery--a prospective
      study.
AB  - The aim of this study was to compare the sensitivity of intraoperative frozen
      section with hematoxyllin-eosin (H&E) staining, immunohistochemistry (IHC) or
      imprint cytology (IC) in the analysis of sentinel node (SN) in breast cancer.
      Towards this end, a prospective study of 102 patients undergoing mastectomy or
      sector resection with SN biopsy was conducted. Frozen sections of SN with H&E,
      IHC staining and IC had sensitivities of 73.5%, 75.5% and 51.0%, respectively.
      The combination of H&E and IHC raised the overall sensitivity to 83.7%.
      Macrometastases (>2 mm) were detected in 100% of the cases with H&E, 92.6% with
      IHC and 81.5% with IC; and micrometastases (2 mm) in 35.0%, 45.0% and 5.0%,
      respectively. The combination of H&E and IHC staining raised the sensitivity to
      55.0%. Frozen-section analysis with H&E staining showed high sensitivity in
      detecting macrometastases but not micrometastases. The sensitivity for detection
      of micrometastases was not substantially increased by the use of intraoperative
      IHC. Imprint cytology did not provide any additional information.

PMID- 16446085
TI  - Effect of polysaccharide extracted from Glaciecola polaris on the protection of
      mouse macrophages from oxidative injury.
AB  - The effect of the protein-bound polysaccharide extracted from Glaciecola polaris
      (PSG) was investigated in vitro in the protection of oxidatively-injured mouse
      macrophages stressed by tert-butyl hydroperoxide (tbOOH) or by oxidatively
      modified low-density lipoprotein (Ox-LDL). The results showed that PSG treatments
      to protect the macrophages from oxidative injury was effective and the macrophage
      colony-stimulating factor (M-CSF) exhibited some similar effects. It was
      speculated that both M-CSF and PSG could protect macrophages from oxidative
      injury. The results suggested that the effects of PSG were associated with its
      capability of inducing M-CSF expression.

PMID- 16446086
TI  - Synthesis and evaluation of NO-release from symmetrically substituted furoxans.
AB  - A series of symmetrically substituted dibenzoyl furoxans were synthesized and
      investigated for their potential to release nitric oxide, which plays a key role
      in the nervous and cardiovascular systems. Cysteine was employed to promote
      nitric oxide release from furoxan via the formation of an S-nitrosothiol
      intermediate. Transition metal ion-mediated S-nitrosocysteine decomposition
      liberates nitric oxide that, in aqueous aerobic solutions, is converted to
      reactive nitrogen oxide species. The percent nitric oxide released was quantified
      colorimetrically by the Griess reagent system.

PMID- 16446087
TI  - Design and structure-activity relationship of heterocyclic analogs of 4-amino-3
      benzimidazol-2-ylhydroquinolin-2-ones as inhibitors of receptor tyrosine kinases.
AB  - Herein are described a series of novel heterocyclic analogs of the 4-amino-3
      benzimidazol-2-ylhydroquinolin-2-one scaffold. These compounds are potent
      inhibitors of receptor tyrosine kinases and exhibit favorable pharmacokinetic
      profiles. The synthesis and SAR of these compounds are described.

PMID- 16446089
TI  - Synthesis and antibacterial activity of 6-O-heteroarylcarbamoyl-11,12
      lactoketolides.
AB  - A new series of erythromycin A derivatives, the 6-O-heteroarylcarbamoyl-11,12
      lactoketolides, with activity against macrolide-resistant streptococci, are
      described. Structurally, these macrolide antibiotics are characterized by a
      heteroaryl side chain attached to the macrolactone core through a carbamate
      linkage at the C6 position, as well as 11,12-gamma-lactone and 3-keto
      functionalities. The synthesis and antibacterial activity of this new series of
      ketolides are discussed.

PMID- 16446088
TI  - Synthesis and transdermal penetration-enhancing activity of carbonic and carbamic
      acid esters--comparison with transkarbam 12.
AB  - Transkarbam 12 (T12) is a novel transdermal penetration enhancer with high
      activity. Its polar head group is formed by carbamic acid salt that is unstable
      in acidic environment and releases CO(2). To find out whether this property
      influences its high activity, two series of compounds with CO(2) stronger bound
      in the polar head have been prepared-carbonic and carbamic acid esters. The
      carbamate salt in the polar head was found to be essential for the enhancing
      activity and its decomposition in an acidic environment suggested relating to the
      mode of action of T12.

PMID- 16446090
TI  - Synthesis and biological evaluation of 1-(2,4,5-trisubstituted phenyl)-3-(5
      cyanopyrazin-2-yl)ureas as potent Chk1 kinase inhibitors.
AB  - Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4
      dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea in the checkpoint kinase 1 (Chk1)
      enzyme, we modified R4, and to a lesser extent, R2, and R5 of the phenyl ring,
      and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity
      less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best
      overall results in the cellular assays as it abrogated doxorubicin-induced cell
      cycle arrest (IC50=1.7 microM) and enhanced doxorubicin cytotoxicity (IC50=0.44
      microM) while displaying no single agent activity.

PMID- 16446091
TI  - Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of
      cathepsin S. Part 3: heterocyclic P3.
AB  - A series of N(alpha)-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were
      identified as potent, selective, and noncovalent inhibitors of cathepsin S.
      Structure-activity relationships including strategies for modulating the
      selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are
      discussed. A X-ray structure of compound 3 bound to the active site of cathepsin
      S is also reported.

PMID- 16446092
TI  - Benzoxazole benzenesulfonamides as allosteric inhibitors of fructose-1,6
      bisphosphatase.
AB  - A series of novel benzoxazole benzenesulfonamides was synthesized as inhibitors
      of fructose-1,6-bisphosphatase (FBPase-1). Extensive SAR studies led to a potent
      inhibitor, 53, with an IC(50) of 0.57microM. Compound 17 exhibited excellent
      bioavailability and a good pharmacokinetic profile in rats.

PMID- 16446093
TI  - Deficits in time-to-boundary measures of postural control with chronic ankle
      instability.
AB  - Our purpose was to examine postural control in single leg stance in subjects with
      and without unilateral chronic ankle instability (CAI) using traditional center
      of pressure (COP)-based and time-to-boundary (TTB) measures. Fifteen physically
      active females with self-reported unilateral chronic ankle instability (CAI) and
      nine healthy female controls performed three 10-s trials of eyes open single limb
      quiet standing on a force plate on both their legs. The traditional measures were
      mean COP velocity, standard deviation of COP, range of COP, and percent of
      available range utilized. The TTB measures were absolute minimum TTB, mean of the
      minimum TTB samples, and standard deviation of the minimum TTB samples. All
      measures were calculated in both the mediolateral (ML) and anteroposterior (AP)
      directions. A 2x2 group (CAI, control) by side (involved, uninvolved) design was
      utilized. The CAI group had significantly lower scores for five of the six TTB
      measures compared to the control group, however only one (AP COP velocity) of the
      eight traditional measures was different between groups. The TTB measures appear
      to detect postural control deficits related to CAI that traditional measures do
      not.

PMID- 16446094
TI  - Evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism
      and the risk of ischaemic stroke.
AB  - Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with
      increased incidence of stroke in some populations, although contradictory results
      have been reported. The aim of this study was to determine the allelic frequency
      and the genotypic distribution for ACE gene polymorphism in Turkish patients with
      ischemic stroke compared to appropriate healthy controls and to correlate the
      genetic findings with stoke type. One hundred and eight patients with ischemic
      stroke versus 79 healthy controls were studied for the presence of ACE gene
      polymorphism detected by PCR. Genotypes were defined as DD, II and ID according
      to the presence of the D (deletion) and I (insertion) alleles. There was no
      statistically significant difference in either the genotypic distribution or
      allelic frequency between the patients versus healthy controls (chi2 = 0.105; df
      = 1; p = 0.430). There was also no significant difference for ACE genotype
      distribution and allelic frequency within the stroke group classified according
      to Bamford criteria (chi2 = 4.827; df = 3; p = 0.185). Our data supports lack of
      association between DD genotype and/or D allele and ischemic stroke or subtypes
      of ischaemic stroke in the Turkish population.

PMID- 16446095
TI  - Aneurysms in children: review of 15 years experience.
AB  - INTRODUCTION: Intracranial aneurysms in children are rare. The location, size,
      age, and presentation in the young are markedly different from that of adults.
      The 15-year experience of the senior author in southern California is presented.
      METHODS: All paediatric patients treated for cerebral aneurysm over a 15-year
      period were identified. Intraoperative and postoperative data were collected
      retrospectively from the medical records. The need for additional surgery as well
      as the incidence of complications including death, hemiparesis, seizures, memory
      disturbances, and the need for subsequent cerebrospinal fluid (CSF) diversion
      were identified. RESULTS: Fifty children were identified (54 lesions).
      Subarachnoid haemorrhage was the most common mode of presentation with the
      average Hunt-Hess grade being I-II. The locations of the lesions were middle
      cerebral (10), internal carotid (8), anterior communicating (7), posterior
      cerebral (6), posterior communicating (5), pericallosal (4), anterior cerebral
      (3), choroidal (3), posterior inferior cerebellar (3), basilar (2), vertebral (2)
      and frontopolar (1) arteries. Clinical vasospasm was encountered in eight of our
      patients, but no cases were observed in those younger than nine years. Long-term
      outcome was excellent in 22 cases, good in 20 and poor in nine, with one death
      and two patients lost to follow-up. CONCLUSION: Analysis of our data suggested a
      predilection for the posterior circulation compared to adults, larger size, more
      complex architecture, and a decreased incidence of clinical vasospasm in the
      younger age group. This series and a review of the literature suggest that
      aneurysmal disease in children may be distinct from that of adults.

PMID- 16446096
TI  - Synthetic melanin is a model for soluble natural eumelanin in UVA-photosensitised
      superoxide production.
AB  - Studies to UV-irradiate natural eumelanins in vitro have used insoluble pigment
      obtained by acid hydrolysis, which lacks melanoprotein. Eumelanin synthesised in
      the presence of a protein is not insoluble, and the insoluble form of melanin
      from acid hydrolysis may not have the same physicochemical properties as the
      natural pigment synthesised in vivo in the melanosome. Here we investigated
      radical production by three natural eumelanins exposed to solar levels of UVA;
      sepia melanin from Sepia officinalis, and eumelanins isolated from Oriental human
      and domestic cat hair. UVA irradiation of sepia melanin in solution at pH 4.5 in
      the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) gave
      hydroperoxyl and hydroxyl radical-adducts, maximal at 0.6-2.5 mg/ml melanin
      concentrations. Hydroperoxyl radical production was relatively low in acetate
      buffer, but detected in aqueous suspensions of sepia melanin. Hair eumelanins
      were photoreactive with hydroperoxyl radical-adduct production at low
      concentrations (0.1-0.4 mg/ml melanin). Synthetic pigment after synthesis
      undergoes photo-oxidation (producing superoxide) at low concentrations (0.3
      mg/ml) and its oxidation increases the photoreactivity at higher melanin
      concentrations. These findings may be physiologically relevant to the properties
      and function of eumelanin in vivo when it is at low concentration (found in a
      small proportion of Caucasian melanocytes), and suggest that synthetic melanin
      has the potential for the basis of a model for natural eumelanin.

PMID- 16446097
TI  - Inactivation of methicillin-resistant Staphylococcus aureus (MRSA) by liposome
      delivered photosensitising agents.
AB  - The uptake of two photosensitising agents (hematoporphyrin and chlorophyll a) by
      a highly pathogenic bacterium, namely methicillin-resistant Staphylococcus aureus
      (MRSA), has been studied by using unilamellar liposomes of different size,
      fluidity and electric charge as carriers. Optimal results are obtained by using
      hematoporphyrin embedded in fluid cationic vesicles composed by the monocationic
      lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate
      (DOTAP), which yield an endocellular concentration of photosensitiser much higher
      than that obtained by incubation of the cells with the free porphyrin, yet
      promote a tighter binding and a more efficient photoinactivation of MRSA.
      Apparently, the photosensitiser is successfully transferred from the liposome to
      the bacterial cells when the presence of the tetrapyrrolic derivative does not
      appreciably perturb the native three-dimensional organisation of the lipid
      vesicle, such as it occurs with hematoporphyrin. On the other hand, chlorophyll,
      which causes a marked structural alteration of the DOTAP vesicles as shown by
      electron microscopy and fluorescence anisotropy measurements, does not show any
      detectable photocytotoxicity toward MRSA, contrary to what observed for the free
      dye.

PMID- 16446098
TI  - Dominulin A and B: two new antibacterial peptides identified on the cuticle and
      in the venom of the social paper wasp Polistes dominulus using MALDI-TOF, MALDI
      TOF/TOF, and ESI-ion trap.
AB  - Two new antibacterial peptides, denominated as Dominulin A and B, have been found
      on the cuticle and in the venom of females of the social paper wasp Polistes
      dominulus. The amino acidic sequence of the two peptides, determined by mass
      spectrometry, is INWKKIAE VGGKIL SSL for Dominulin A (MW = 1854 Da) and
      INWKKIAEIGKQVL SAL (MW = 1909 Da) for Dominulin B. Their presence on the cuticle
      was confirmed using MALDI-TOF by means of micro-extractions and direct analyses
      on body parts. The presence in the venom and the primary structure of the
      dominulins suggest their classification in the mastoparans, a class of peptides
      found in the venom of other Aculeate hymenoptera. Their antimicrobial action
      against Gram+ and Gram- bacteria fits in the range of the best natural
      antimicrobial peptides. Dominulins can represent an important defense of the
      colony of Polistes dominulus against microbial pathogens.

PMID- 16446099
TI  - Improving the quality of the ion beam exiting a quadrupole ion guide.
AB  - The effect of fringing fields on the divergence of the ion beam exiting an RF
      quadrupole ion guide was studied using a computer simulation. It was shown that
      reducing the strength of the RF field towards the ion guide exit reduces ion beam
      divergence. Further improvement was demonstrated when creating a DC gradient
      towards the exit. The results of the numerical simulation were verified
      experimentally using a time-of-flight (TOF) mass analyzer with orthogonal
      acceleration. Decreasing the ion beam divergence resulted in considerably
      improved mass resolution of the instrument.

PMID- 16446100
TI  - Exosomes are released by cultured cortical neurones.
AB  - Accumulating evidence shows that several cell types have the capacity to secrete
      membrane proteins by incorporating them into exosomes, which are small lipid
      vesicles derived from the intralumenal membranes of multivesicular bodies (MVBs)
      of the endocytic pathway. Exosomes are expelled in the extracellular space upon
      fusion of the MVB with the plasma membrane. Exosomal release is a way of
      secreting membrane proteins meant to be discarded, or to be passed on to other
      cells. Here, we demonstrate, using primary cortical cultures, that neurones and
      astrocytes can secrete exosomes. We find that exosomes released by cortical
      neurones contain the L1 cell adhesion molecule, the GPI-anchored prion protein,
      and the GluR2/3 but not the NR1 subunits of glutamate receptors. We also show
      that exosomal release is regulated by depolarisation. Our observation suggests
      that exosomes may have a regulatory function at synapses and could also allow
      intercellular exchange of membrane proteins within the brain.

PMID- 16446101
TI  - Brain-specific factors in combination with mutant huntingtin induce gene-specific
      transcriptional dysregulation.
AB  - Mutant huntingtin lowered steady-state levels of DARPP-32 mRNA in the brain but
      not kidney of R6 transgenic HD mice by repressing transcription from one of two
      promoters. The activity of DARPP-32 promoter deletion constructs were lower in
      the presence of mutant huntingtin in immortalized striatal cell lines but no
      difference in transcription factor binding to the promoter was detected. The
      activity of CMV, TK and HPRT promoters was also affected by mutant huntingtin in
      these cell lines. Transient transfection experiments demonstrated that short-term
      expression of mutant huntingtin exerted a cell- and promoter-specific
      transcriptional repression. In in vitro experiments, transcription of the CMV
      promoter was reduced in the presence of striatal proteins and mutant huntingtin.
      It is likely that select combinations of trans-acting factors, co-activators and
      components of the Pol II holoenzyme acting in concert provide the basis for both
      the gene- and tissue-specific effects of mutant huntingtin.

PMID- 16446102
TI  - Checking the conformational stability of cystatin C and its L68Q variant by
      molecular dynamics studies: why is the L68Q variant amyloidogenic?
AB  - Human L68Q cystatin C is one of the known human amyloidogenic proteins. In its
      native state it is a monomer with alpha/beta structure. Experimental evidence
      suggests that L68Q variant associates into dimeric intermediates and that the
      dimers subsequently self-assemble to form amyloid deposits and insoluble fibrils.
      Details of the pathway of L68Q mutant amyloid formation are unclear; however,
      different experimental approaches with resolutions at molecular level have
      provided some clues. Probably, the stability and flexibility of monomeric L68Q
      variant play essential roles in the early steps of amyloid formation; thus, it is
      necessary to characterize early conformational changes of L68Q cystatin C
      monomers. In this paper, we demonstrate the possibility that the differences
      between the monomeric forms of wild-type (wt) cystatin C and its L68Q variant are
      responsible for higher tendency of the L68Q cystatin C amyloidogenesis. We
      started our studies with the simulations of wt and L68Q cystatin C monomers.
      Nanosecond time scale molecular dynamics simulations at 308K were performed using
      AMBER7.0 program. The results show that the structure of the L68Q monomer was
      changed, relative to the wt cystatin C structure. The results support earlier
      speculation that the L68Q point mutation would easily lead to dimer formation.

PMID- 16446103
TI  - Optic nerve atrophy and retinal nerve fibre layer thinning following optic
      neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy.
AB  - Magnetic resonance imaging (MRI) measures of brain atrophy are often considered
      to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited.
      Optic neuritis is a common manifestation of MS and results in optic nerve
      atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of
      detecting axonal loss following optic neuritis. We hypothesise that if the optic
      nerve atrophy that develops following optic neuritis is contributed to by axonal
      loss, it will correlate with thinning of the RNFL. Twenty-five patients were
      studied at least 1 year after a single unilateral attack of optic neuritis
      without recurrence, with a selection bias towards incomplete recovery. They had
      MR quantification of optic nerve cross-sectional area and optic nerve lesion
      length, as well as optical coherence tomography (OCT) measurement of mean RNFL
      thickness and macular volume, quantitative visual testing, and visual evoked
      potentials (VEPs). Fifteen controls were also studied. Significant optic nerve
      atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33%
      versus controls), and macular volume loss occurred in patients' affected eyes
      when compared with patients' unaffected eyes and healthy controls. The optic
      nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual
      acuity, visual field mean deviation, and whole field VEP amplitude but not
      latency. These findings suggest that axonal loss contributes to optic nerve
      atrophy following a single attack of optic neuritis. By inference, axonal loss
      due to other post-inflammatory brain lesions is likely to contribute to the
      global MRI measure of brain atrophy in multiple sclerosis.

PMID- 16446104
TI  - Event-related functional near-infrared spectroscopy (fNIRS): are the measurements
      reliable?
AB  - The purpose of the present study was to investigate the retest reliability of
      event-related functional near-infrared spectroscopy (fNIRS). Therefore, isolated
      functional activation was evoked in the occipital cortex by a periodic
      checkerboard stimulation. During a 52-channel fNIRS recording, 12 subjects
      underwent 60 trials of visual stimulation in two sessions. The retest interval
      was set to 3 weeks. Linear correlations of the contrast t values supplemented by
      scatter plots, channel-wise intraclass correlation coefficients (ICC) as well as
      reproducibility indices for the quantity of activated channels (RQUANTITY) and
      the location (ROVERLAP) of the detected activation were calculated. The results
      at the group level showed good reliability in terms of the single measure ICCs
      (up to 0.84) and excellent reproducibility quantified by RQUANTITY and ROVERLAP
      (up to 96% of the quantity and the location were reproducible), whereas the
      results at the single subjects' level were mediocre. Furthermore, the reliability
      assessed by single measurement ICCs improved if regarded at a cluster level.

PMID- 16446105
TI  - Phylogeny of the tungara frog genus Engystomops (= Physalaemus pustulosus species
      group; Anura: Leptodactylidae).
AB  - We present a phylogeny of the Neotropical genus Engystomops (= Physalaemus
      pustulosus species group) based on sequences of approximately 2.4 kb of mtDNA,
      (12S rRNA, valine-tRNA, and 16S rRNA) and propose a phylogenetic nomenclature.
      The phylogeny includes all described taxa and two unnamed species. All analyses
      indicate that Engystomops is monophyletic and contains two basal allopatric
      clades. Clade I (Edentulus) includes E. pustulosus and the Amazonian E. petersi +
      E. cf. freibergi. Clade II (Duovox) includes all species distributed in W Ecuador
      and NW Peru. Brevivox, a clade of small-sized species is strongly supported
      within Duovox. Populations of Engystomops pustulosus fall into two well-supported
      clades, each of which occupies two disjunct portions of the species range.
      Overall, our phylogeny is congruent with most previous hypotheses. This study is
      among the few published species-level phylogenies of Neotropical amphibians
      derived from molecular datasets. A review of the proportion of new species
      detected by similar studies suggests that the increasing use of molecular
      techniques will lead to the discovery of a vast number of species of Neotropical
      amphibians.

PMID- 16446106
TI  - Complete nucleotide sequence of the mitochondrial genome of a Malagasy poison
      frog Mantella madagascariensis: evolutionary implications on mitochondrial
      genomes of higher anuran groups.
AB  - We determined the complete nucleotide sequence of the mitochondrial (mt) genome
      of a Malagasy poison frog, Mantella madagascariensis (family Mantellidae), and
      partial sequences of two Mantella (M. baroni and M. bernhardi) and two additional
      mantellid species (Boophis madagascariensis and Mantidactylus cf. ulcerosus). The
      M. madagascariensis genome was shown to be the largest (23kbp) of all vertebrate
      mtDNAs investigated so far. Furthermore, the following unique features were
      revealed: (1) the positions of some genes and gene regions were rearranged
      compared to mitochondrial genomes typical for vertebrates and other anuran
      groups, (2) two distinct genes and a pseudogene corresponding to transfer RNA
      gene for methionine (tRNA-Met) were encoded, and (3) two control regions with
      very high sequence homology were present. These features were shared by the two
      other Mantella species but not the other mantellid species, indicating dynamic
      genome reorganization in a common ancestor linage before divergence of the
      Mantella genus. The reorganization pathway could be explained by a model of gene
      duplication and deletion. Duplication and deletion events also seem to have been
      responsible for concerted sequence evolution of the control regions in Mantella
      mt genomes. It is also suggested that the pseudo tRNA-Met gene sustained for a
      long time in Mantella mt genomes possibly functions as a punctuation marker for
      NADH dehydrogenase subunit (ND) 2 mRNA processing. Phylogenetic analyses
      employing a large sequence data set of mt genes supported the monophyly of
      Mantellidae and Rhacophoridae and other recent phylogenetic views for ranoid
      frogs. The resultant phylogenetic relationship also suggested parallel occurrence
      of two tRNA-Met genes, duplicated control regions, and ND5 gene translocation in
      independent ranoid lineages.

PMID- 16446108
TI  - The pain self-efficacy questionnaire: Taking pain into account.
AB  - Self-efficacy beliefs in people with chronic pain have been assessed either by
      reference to confidence in ability to perform specific tasks or to confidence in
      performing more generalised constructs like coping with pain. Both approaches
      reflect aspects of the original conceptualisations of self-efficacy and both have
      proved useful, but it is noteworthy that confidence in performing activities in
      the context of pain is rarely addressed. An important element in the original
      formulations of self-efficacy referred to persistence in the face of obstacles
      and aversive experiences. In this context, self-efficacy beliefs for people
      experiencing chronic pain might be expected to incorporate not just the
      expectation that a person could perform a particular behaviour or task, but also
      their confidence in being able to do it despite their pain. This aspect of the
      self-efficacy construct has been included in a measure for people with chronic
      pain, the Pain Self-Efficacy Questionnaire (PSEQ). The accumulated evidence from
      a number of published studies and a confirmatory analysis with a large cohort of
      heterogeneous chronic pain patients attending a pain management program provide
      support for the PSEQ's original psychometric properties developed with a sample
      of chronic low back pain patients. The importance of taking the context of pain
      into account in the assessment of self-efficacy beliefs in pain populations and
      the ways in which this measure can be used to improve the assessment of people
      experiencing chronic pain, before and after treatment, are examined.

PMID- 16446107
TI  - Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in association
      with severe iron overload, and one with sideroblastic anemia and severe iron
      overload.
AB  - Mutations in aminolevulinate synthase 2 (ALAS2) are usually associated with
      sideroblastic anemia and iron overload. The objective of this study was to
      determine if "mild" mutations in ALAS2 might increase the severity of primary
      iron overload. Direct sequencing of the ALAS2 gene was performed on 24 subjects
      with primary hemochromatosis and one subject with sideroblastic anemia with
      severe iron overload. We identified a novel mutation P520L (c. 1559 C --> T) in
      ALAS2 in three subjects. Two had severe iron overload and no anemia: one also had
      HFE C282Y homozygosity, and the other was wildtype for HFE and other iron-related
      genes. The third subject had sideroblastic anemia with iron overload, and was
      hemizygous for both P520L and R560H (c. 1679 G --> A) mutations in ALAS2. The
      P520L mutation was found at a frequency of 0.0013 (741 alleles) in white control
      subjects, but was not found in 158 alleles from black control subjects. The
      proline in this position is highly conserved across species from humans to
      zebrafish. However, genotype/phenotype studies of the families demonstrate that
      the P520L mutation alone has no iron-associated phenotype, but it may act as a
      modifier of iron overload in the presence of mutations in HFE or other
      uncharacterized hemochromatosis genes. Thus, ALAS2 mutations might contribute to
      more severe iron loading in persons with primary hemochromatosis.

PMID- 16446109
TI  - Discrimination of cerebral ischemic states using bispectrum analysis of EEG and
      artificial neural network.
AB  - No doubt a noninvasive technique for detection of cerebral ischemic extent,
      before the formation of the focus, is extremely valuable. This paper presents a
      new approach to early evaluate the degree of ischemic injury by combining
      bispectrum estimation of electroencephalograms (EEGs) with artificial neural
      network (ANN). The graded ischemic injuries in 24 Sprague-Dawley (SD) rats were
      induced for different periods of 8, 18, 30 min by infusing physiological saline
      along the left blood stream, based on the model for rat ischemic cerebral injury
      described in this paper. Four channels of EEG were collected in each rat at
      scheduled time of ischemia. The maximum bicoherence index and the weighted center
      of bispectrum (WCOB) were extracted from the EEGs and were used as input feature
      vector of a four-layer (12-7-2-1) ANN for prediction. Training and testing the
      ANN used the 'leave one out' strategy. The levels of ischemic injury were
      verified and classified by observing the ischemic area by conventional
      hematoxylin and eosin (HE) staining and the heat shock protein (HSP70) test. The
      proposed method was able to correctly detect ischemic extent in average accuracy
      of 91.67% of the cases. The results show that this scheme can be expected to
      diagnose ischemic cerebral injury in its earlier phases.

PMID- 16446110
TI  - VIM deep brain stimulation does not improve pre-existing restless legs syndrome
      in patients with essential tremor.
AB  - The neuroanatomic substrate for restless legs syndrome (RLS) is not known. We
      implanted deep brain stimulators into the ventralis intermedius nucleus (VIM) of
      the thalamus in nine subjects for essential tremor (ET) whom all concurrently had
      RLS. Although the VIM DBS improved tremor, none of the subjects felt there was
      any meaningful effect on their RLS symptoms. The VIM thalamus, which is involved
      in ET and Parkinson's disease, does not seem to be primarily involved in RLS.

PMID- 16446111
TI  - Pathways of disulfide bond formation in Escherichia coli.
AB  - Disulfide bond formation is required for the correct folding of many secreted
      proteins. Cells possess protein-folding catalysts to ensure that the correct
      pairs of cysteine residues are joined during the folding process. These enzymatic
      systems are located in the endoplasmic reticulum of eukaryotes or in the
      periplasm of Gram-negative bacteria. This review focuses on the pathways of
      disulfide bond formation and isomerization in bacteria, taking Escherichia coli
      as a model.

PMID- 16446112
TI  - What the patient wore, and why ...
AB  - This study set out to compare the wearing habits and attitudes of patients today
      with those, featured in a study by Cross, fitted prior to 1949. Information was
      sought in the present time regarding the age, occupation and sex of the wearers
      in 10 different categories of lens types currently available. The views of the
      patients were also sought regarding the comfort, distance vision, close vision,
      convenience and how the present lenses met their expectations. Motivation to wear
      contact lenses was also compared between the two studies. Results show a
      considerable change in the age of wearers both at the time of fitting and at the
      time of the studies, occupations of the wearers, and wearing modalities. Most of
      all it highlights the huge amount of choice available to the modern wearer, not
      only in lens types and materials, but also in the location and type of practice
      fitting lenses now at very much lower costs. Wearing times tend to have dropped
      since 1949 but through choice rather than necessity.

PMID- 16446113
TI  - Infectious diseases - a global challenge.
AB  - Infectious diseases represent a continuous and increasing threat to human health
      and welfare. Due to emerging diseases, increasing resistances, international
      travelling, and the risk of bioterroristic attacks, infectious diseases concern
      the whole world and can only be combated by internationally coordinated and
      interdisciplinary approaches. When assessing the worldwide publication activities
      on infectious diseases in the years 1994-2004 accessible via the ISI Science
      Citation Index Expanded, an overall increase by 24% can be monitored.
      Furthermore, it becomes evident that highest research priorities are given to
      HIV/AIDS, hepatitis C, tuberculosis, respiratory infections, and sepsis. Ten
      countries - including the USA, the UK, France, Germany, and Japan - contributed
      to more than 80% of these publications; nation-specific research priorities
      focusing on the current problems in the respective country can be estimated.
      Countries with the highest disease burdens are still not given the opportunity to
      contribute adequately to the scientific field. Based on our data, relatively
      increasing publication activities include those on respiratory infections,
      tuberculosis, malaria, hepatitis, and sepsis, whereas decreasing activities were
      determined for AIDS, diarrhoea, meningitis, schistosomiasis, and other diseases.
      Accordingly, the prevalence of many infectious diseases occurring in tropical
      countries is not clearly reflected in the worldwide publication activities.

PMID- 16446114
TI  - Leishmania proteins derived from recombinant DNA: current status and next steps.
AB  - The parasite Leishmania is a major cause of disease worldwide. In the past 15
      years, many groups have analysed DNA-derived proteins from Leishmania. Large
      amounts of data obtained by these groups can be collated to direct future
      research into Leishmania and to find novel immunological mechanisms and
      information about its metabolism. International coordination will increase both
      the basic knowledge about Leishmania and the capacity to apply this knowledge to
      combat leishmaniases.

PMID- 16446115
TI  - The conundrum of CD40 function: host protection or disease promotion?
AB  - T cells regulate the immune responses to pathogens and autoantigens. The immune
      responses are tolerizing or anti-inflammatory against autoantigens but are
      inflammatory against pathogens and allografts. Such contradictory immune
      responses have been attributed to two counteracting effector cell types or to two
      counterregulatory sets of molecules: cell-surface expressed or secreted. By
      contrast, recent reports suggest that CD40, a co-stimulatory molecule on antigen
      presenting cells, is a crucial controller of these counteractive immune
      responses, and emphasize reciprocal inhibition as an essential feature of
      biological responses. The molecular mechanism of such reciprocity in CD40
      functions is the basis of immunotherapy in many diseases.

PMID- 16446117
TI  - Further thoughts on where we stand on the autoimmunity hypothesis of Chagas
      disease.

PMID- 16446116
TI  - Toxoplasmosis: beyond animals to humans.
AB  - The parasitic zoonosis toxoplasmosis, which was poorly understood before the
      advent of the HIV epidemic, has become a major clinical problem worldwide. Humans
      acquire toxoplasmosis from cats, from consuming raw or undercooked meat and from
      vertical transmission to the foetus through the placenta during pregnancy.
      Studies of the unique environmental factors in various communities indicate the
      important roles that eating habits and culture have on the transmission of this
      infection. The socioepidemiological aspects of toxoplasmosis are thought to be
      important contributing factors for the spread of this disease. Preventative
      measures should consider the cultures and beliefs of people in various
      communities more than solving poverty and giving orthodox health education.

PMID- 16446118
TI  - An Australian network to support the understanding and control of parasites.
AB  - The Australian Research Council (ARC) and the National Health and Medical
      Research Council (NHMRC) Research Network for Parasitology will focus and
      coordinate the fundamental, strategic and applied parasitology research in
      Australia. It will raise the standing of Australia in the field, assist in the
      community understanding of parasitology, and maintain and improve the capacity of
      Australia to keep its stock, crops, wildlife and people free from disease. On an
      international scale, the ARC/NHMRC Network will work with other countries to
      develop new technologies for the detection and control of parasites.

PMID- 16446119
TI  - Unusual features in eyelid myoclonia with absences: a patient with mild mental
      retardation and background slowing on electroencephalography.
AB  - "Eyelid myoclonia with and without absences" has been incorporated into the new
      ILAE diagnostic scheme as a type of epileptic seizure with etiologic,
      therapeutic, and prognostic implications. Eyelid myoclonia with absences (EMA) is
      characterized by eyelid myoclonia and absences provoked mainly by eye closure and
      photosensivity. EMA can be a part of idiopathic, symptomatic, or probably
      symptomatic epileptic syndromes. EMA is the defining seizure symptom that
      differentiates the idiopathic reflex epileptic syndrome Jeavons syndrome from
      eyelid myoclonia with absences. Jeavons syndrome is characterized by unique
      clinical and electroencephalographic features and often genetic clustering. EMA
      is easily diagnosed by clinical manifestations and properly conducted
      electroencephalography. However, it is often misdiagnosed as tics or other types
      of epileptic seizures and syndromes, particularly in patients with mental
      retardation, behavioral disturbances, and atypical electroencephalographic
      findings. We describe a 19-year-old woman with EMA who remained undiagnosed for
      many years. She was mildly mentally retarded and her electroencephalogram showed
      slow background activity, which are unusual findings in Jeavons syndrome.

PMID- 16446120
TI  - The importance of parental expectations of cognitive improvement for their
      children with epilepsy prior to starting the ketogenic diet.
AB  - Although the success rates and complications of various treatment options for
      children with intractable epilepsy have been described, the actual expectations
      of parents for these treatments are less clear. Since 1998, parents at our
      institution have written their goals in a letter before starting their children
      on the ketogenic diet. One hundred consecutive letters were evaluated. The most
      common first goal was seizure improvement, second was anticonvulsant reduction,
      and third was cognitive improvement. Ninety percent requested improvement in
      cognition or alertness. These expectations were either met or exceeded at 6
      months in 52-60% of children. Achieving or surpassing parental expectations for
      cognitive improvement correlated with longer diet duration (P=0.04), but meeting
      goals for seizure or anticonvulsant reduction did not. Cognitive improvement
      (P<0.001) and >90% seizure reduction (P=0.04) at 6 months positively correlated
      with longer eventual diet duration. Expectations for cognitive improvement need
      to be discussed prior to beginning the ketogenic diet.

PMID- 16446121
TI  - Erectile dysfunction associated with pregabalin add-on treatment in patients with
      partial seizures: five case reports.
AB  - Sexual dysfunction has been reported in both men and women with epilepsy.
      Associated factors are diverse but include, among others, antiepileptic drugs. We
      present the cases of 5 men who reported mild to moderate erectile dysfunction or
      impotence for the first time when treated with the new antiepileptic drug
      pregabalin as add-on therapy.

PMID- 16446122
TI  - Spatiotemporal expression of zebrafish keratin 18 during early embryogenesis and
      the establishment of a keratin 18:RFP transgenic line.
AB  - Zebrafish cytokeratin 18 (K18) is one of the type I keratin genes expressed the
      earliest after amputation of the zebrafish fin, but its spatiotemporal expression
      during early development is unclear. Whole-mount in situ hybridization revealed
      that k18 was a maternally inherited gene and that its expression is restricted to
      the single layer of enveloping cells on the surface of embryos during the
      gastrula stage. At later stages, K18 expression was detected in the epithelial
      cells, pronephric duct, digestive tract, dorsal aorta, and fins. By using
      microinjection, we generated the transgenic line Tg(k18(2.9):RFP), which carries
      an upstream 2.9-kb segment of k18 gene fused with a red fluorescent protein (RFP)
      reporter. The spatiotemporal distributions of red fluorescent signal of
      Tg(k18(2.9):RFP) line correlated well with endogenous k18 transcripts detected by
      whole-mount in situ hybridization, indicating that this line is capable of
      recapitulating endogenous k18 expression patterns. We noticed that the red
      fluorescence appeared strongly in the dorsal, pectoral, pelvic, anal, and caudal
      fins when transgenic fish became adults. Interestingly, we also found that when
      F1 female from the Tg(k18(2.9):RFP) line were mated with wild-type males, 100%
      (326/326) of F2 offspring expressed red fluorescence at the one-cell stage. In
      contrast, when F1 male from the Tg(k18(2.9):RFP) line were mated with wild-type
      females, only 49.8% (138/277) of F2 embryos exhibited red fluorescence. On the
      basis of these findings, we suggest that the transcript of zebrafish K18 is
      inherited as a maternal effect. We believe that Tg(k18(2.9):RFP) fish should be
      an excellent experimental animal for studying the zygotic regulatory mechanism of
      k18.

PMID- 16446124
TI  - Repair of thymine glycol by hNth1 and hNeil1 is modulated by base pairing and cis
      trans epimerization.
AB  - Oxidation of thymine yields 5,6-dihydroxy-5,6-dihydrothymine (thymine glycol. Tg)
      which, as cis 5S,6R and 5R,6S 2'-deoxyribonucleoside diastereoisomers (dTg1,
      dTg2), are in equilibrium with their trans 5S,6S and 5R,6R epimers. The
      stereoselective excision of Tg from DNA by the mammalian orthologs of E. coli DNA
      N-glycosylase/AP lyases Nth and Nei was reported using substrates in which Tg
      opposed adenine. Since we showed that Tg is the major product of oxidation of 5
      methylcytosine, we asked if the opposing purine influenced stereospecific
      enzymatic excision. The human ortholog hNth1 released Tg2 much more rapidly than
      Tg1 regardless of the opposing purine. In contrast, hNeil1 released Tg non
      stereoselectively, but the rate of excision was much greater when Tg opposed
      guanine. Remarkably, the kinetics of excision of Tg by hNth1 and hNeil1 were
      biphasic, describing a double exponential curve which yielded two rate constants.
      We suggest that the greater rate constant describes the rate of enzymatic
      excision of Tg. The smaller rate constant represents the equilibrium constant for
      the cis and trans epimerization of dTg1 and dTg2 in high molecular weight DNA.
      Thus, only one of the epimers of dTg1 and dTg2 are enzymatically processed but it
      is not yet known whether it is cis or trans. Thus, base excision repair of Tg in
      mammals is mediated by at least two DNA N-glycosylase/AP lyases which are
      affected by the nature of the diastereoisomer of dTg, the rate of cis-trans
      epimerization of each diastereoisomer, and the nature of the opposing purine.

PMID- 16446123
TI  - Eph receptors and their ephrin ligands are expressed in developing mouse
      pancreas.
AB  - Pancreas development involves branching morphogenesis concomitantly to
      differentiation of endocrine, exocrine and ductal cell types from a single
      population of pancreatic precursors. These processes depend on many signals and
      factors that also control development of the central nervous system. In the
      latter, Eph receptors and their class-A (GPI-anchored) and class-B
      (transmembrane) ephrin ligands control cell migration and axon-pathfinding, help
      establish regional patterns and act as labels for cell positioning. This raised
      the question as to whether and where Ephs and ephrins are expressed during
      pancreas development. Here we have identified the Eph and ephrin genes that are
      expressed in mouse embryonic pancreas, as detected by RT-PCR analysis. In situ
      hybridization experiments showed that Ephs and ephrins are mainly expressed in
      the burgeoning structures of the epithelium which differentiate into exocrine
      acini. Binding experiments on whole pancreas demonstrated the presence of
      functional Eph receptors. They showed that EphBs are expressed by the pancreatic
      epithelium at embryonic day (e) 12.5 and that, from e14.5 on, Ephs of both
      classes are expressed by the pancreatic epithelium and then become restricted to
      developing acini. We conclude that specific members of the Eph/ephrin family are
      expressed in embryonic pancreas according to a dynamic temporal and regional
      pattern.

PMID- 16446125
TI  - Local control of pulmonary blood flow and lung structure in reptiles:
      implications for ventilation perfusion matching.
AB  - Lung structure of reptiles is very diverse ranging from single chambered lungs
      with a simple structure to more complex and multi-chambered lungs. Increased
      structural complexity resulted from the evolution of smaller gas exchange units
      and larger surface area, which increases the pulmonary diffusive capacity for
      O(2). However, increased structural complexity probably also increases the
      possibilities for ventilation-perfusion (V /Q ) heterogeneity, which exerts
      significant constraints on gas exchange. In most reptiles, the ventricle is
      anatomically and functionally undivided so blood pressures are equal in the
      systemic and pulmonary circulations. In these species, blood flow distribution
      between pulmonary and systemic circulations are primarily determined by pulmonary
      and systemic vascular resistances. Thus, increased pulmonary resistance lowers
      pulmonary blood flow through increasing cardiac right-to-left shunt decreasing
      systemic oxygen levels. It has been proposed that local mechanisms regulating
      pulmonary blood flow are more pronounced in reptiles with complex lungs as they
      are more prone to V /Q heterogeneity. However, local control of pulmonary blood
      flow has also been suggested to primarily exist when hearts are functionally
      divided because altered pulmonary vascular resistance does not affect cardiac
      shunt patterns. Data suggest that, while there seems to be a general trend of
      increased local regulation of pulmonary blood flow in species with structurally
      complex lungs and divided hearts, it is also possible that other factors, such as
      breathing pattern, have been important for the evolutionary development of local
      regulatory mechanisms in the lungs.

PMID- 16446126
TI  - Expiratory muscles modulate negative expiratory pressure-induced flow during
      muscular exercise.
AB  - The recruitment of expiratory muscles during exercise might be altered by the
      application of negative expiratory pressure (NEP) inducing a feature of
      expiratory flow limitation (EFL) called muscle EFL. To check this hypothesis EFL
      and expiratory muscle EMG (ExpEMG) were measured at rest and during exercise in
      eight healthy subjects. Six subjects performed isocapnic hyperventilation. At
      5hPa NEP, 5/8 subjects had EFL during exercise. This limitation disappeared when
      NEP value was increased and did not appear during isocapnic hyperventilation.
      During exercise, in limited subjects, ExpEMG was significantly reduced during
      expiration with NEP as compared to control. Gastric pressure measured in a
      limited subject increased during expiration but less with NEP than without it,
      while this pressure measured in another, non-limited, subject decreased. An
      inhibitory reflex due to negative pressure could be responsible for muscle EFL by
      reducing expiratory muscle activity. The response to NEP during exercise should
      be interpreted with caution.

PMID- 16446127
TI  - Developmental plasticity of ventilatory control in zebrafish, Danio rerio.
AB  - To determine whether development of ventilatory control in zebrafish (Danio
      rerio) exhibits plasticity, embryos were exposed to hypoxia, hyperoxia or
      hypercapnia for the first 7 days post-fertilization. Their acute reflex breathing
      responses to ventilatory stimuli (hypoxia, hypercapnia and external cyanide) were
      assessed when they had reached maturity (3 months or older). Zebrafish reared
      under hyperoxic conditions exhibited significantly higher breathing frequencies
      at rest (283+/-27min(-1) versus 212+/-16min(-1) in control fish); breathing
      frequency was unaffected in adult fish subjected to hyperoxia for 7 days. The
      respiratory responses of fish reared in hyperoxic water to acute hypoxia,
      hypercapnia or external cyanide were blunted (hypoxia, cyanide) or eliminated
      (hypercapnia). Adult fish exposed for 7 days to hyperoxia showed no change in
      acute responses to these stimuli. The respiratory responses to acute hypoxia,
      hypercapnia or external cyanide of fish reared under hypoxic or hypercapnic
      conditions were similar to those in fish reared under normal conditions. A subset
      of all fish examined exhibited episodic breathing; an analysis of breathing
      patterns demonstrated that fish reared under hypercapnic conditions had an
      increased tendency to display episodic breathing. The results of this study
      reveal that there is flexibility in the design and functioning of the embryonic
      or larval respiratory system in zebrafish.

PMID- 16446128
TI  - Dried blood spot liquid chromatography assay for therapeutic drug monitoring of
      metformin.
AB  - The use of blood spot collection cards is a simple way to obtain specimens for
      analysis of drugs for the purpose of therapeutic drug monitoring, assessing
      adherence to medications and preventing toxicity in routine clinical setting. We
      describe the development and validation of a microanalytical technique for the
      determination of metformin from dried blood spots. The method is based on
      reversed phase high-performance liquid chromatography with ultraviolet detection.
      Drug recovery in the developed method was found to be more than 84%. The limits
      of detection and quantification were calculated to be to be 90 and 150 ng/ml,
      respectively. The intraday and interday precision (measured by CV%) was always
      less than 9%. The accuracy (measured by relative error, %) was always less than
      12%. Stability analysis showed that metformin is stable for at least 2 months
      when stored at -70 degrees C. The small volume of blood required (10 microL),
      combined with the simplicity of the analytical technique makes this a useful
      procedure for monitoring metformin concentrations in routine clinical settings.
      The method is currently being applied to the analysis of blood spots taken from
      diabetic patients to assess adherence to medications and relationship between
      metformin level and metabolic control of diabetes.

PMID- 16446129
TI  - High-performance liquid chromatography spectrometric analysis of trans
      resveratrol in rat plasma.
AB  - A HPLC method for determination of trans-resveratrol concentrations in rat plasma
      was developed. Plasma samples were treated with acetonitrile to deposit proteins.
      The analysis used a Hypersil ODS(2) C(18) column (5 microm, 4.6 mm x 250 mm) and
      methanol/distilled water as the mobile phase (flow-rate=1 mL/min). The UV
      detection wavelength was 303 nm, and chlorzoxazone was used as the internal
      standard. The calibration curve was linear over the range of 0.02-40 microg/mL
      with a correlation coefficient of 0.9997. This concentration range corresponds
      well with the plasma concentrations of resveratrol in pharmacokinetic studies.
      There was 98.7%, 91.3% and 84.4% recovery from 0.02, 0.4 and 40 microg/mL plasma
      samples respectively. The R.S.D. of intra- and inter-day assay variations were
      all less than 12%. This HPLC assay is a quick, precise and reliable method for
      the analysis of resveratrol in pharmacokinetic studies.

PMID- 16446130
TI  - Protein conformation determines the sensibility to high pressure treatment of
      infectious scrapie prions.
AB  - Application of high pressure can be used for gentle pasteurizing of food,
      minimizing undesirable alterations such as vitamin losses and changes in taste
      and color. In addition, pressure has become a useful tool for investigating
      structural changes in proteins. Treatments of proteins with high pressure can
      reveal conformations that are not obtainable by other physical variables like
      temperature, since pressure favors structural transitions accompanied with
      smaller volumes. Here, we discuss both the potential use of high pressure to
      inactivate infectious TSE material and the application of this thermodynamic
      parameter for the investigation of prion folding. This review summarizes our
      findings on the effects of pressure on the structure of native infectious scrapie
      prions in hamster brain homogenates and on the structure of infectious prion rods
      isolated from diseased hamsters brains. Native prions were found to be pressure
      sensitive, whereas isolated prions revealed an extreme pressure-resistant
      structure. The discussion will be focused on the different pressure behavior of
      these prion isoforms, which points out differences in the protein structure that
      have not been taken into consideration before.

PMID- 16446131
TI  - Folding studies of two hydrostatic pressure sensitive proteins.
AB  - High hydrostatic pressure combined with various spectroscopies is a powerful
      technique to study protein folding. An ideal model system for protein folding
      studies should have the following characteristics. (1) The protein should be
      sensitive to pressure, so that the protein can be unfolded under mild pressure.
      (2) The folding process of the protein should be easily modulated by several
      chemical or physical factors. (3) The folding process should be easily monitored
      by some spectroscopic parameters. Here, we summarized the pressure induced
      folding studies of two proteins isolated from spinach photosystem II, namely the
      23-kDa and the 33-kDa protein. They have all the characteristics mention above
      and might be an ideal model protein system for pressure studies.

PMID- 16446132
TI  - Pressure and temperature as tools for investigating the role of individual non
      covalent interactions in enzymatic reactions Sulfolobus solfataricus
      carboxypeptidase as a model enzyme.
AB  - Sulfolobus solfataricus carboxypeptidase, (CPSso), is a heat- and pressure
      resistant zinc-metalloprotease. Thanks to its properties, it is an ideal tool for
      investigating the role of non-covalent interactions in substrate binding. It has
      a broad substrate specificity as it can cleave any N-blocked amino acid (except
      for N-blocked proline). Its catalytic and kinetic mechanisms are well understood,
      and the hydrolytic reaction is easily detectable spectrophotometrically. Here, we
      report investigations on the pressure- and temperature-dependence of the kinetic
      parameters (turnover number and Michaelis constant) of CPSso using several
      benzoyl- and 3-(2-furyl)acryloyl-amino acids as substrates. This approach enabled
      us to study these parameters in terms of individual rate constants and establish
      that the release of the free amino acid is the rate-limiting step, making it
      possible to dissect the individual non-covalent interactions participating in
      substrate binding. In keeping with molecular docking experiments performed on the
      3D model of CPSso available to date, our results show that both hydrophobic and
      energetic interactions (i.e., stacking and van der Waals) are mainly involved,
      but their contribution varies strongly, probably due to changes in the
      conformational state of the enzyme.

PMID- 16446133
TI  - The ups and downs of BDNF in Rett syndrome.
AB  - Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder, which
      is primarily caused by mutations in the gene encoding methyl-CpG binding protein
      2 (MeCP2). A number of MeCP2 target genes have been identified, including the
      neurotrophic factor BDNF; however, the functional relevance of these targets has
      not been established. In this issue of Neuron, Chang et al. provide the first in
      vivo evidence for a functional interaction between BDNF and MeCP2.

PMID- 16446134
TI  - Think globally, act locally: local translation and synapse formation in cultured
      Aplysia neurons.
AB  - Synapse formation is initiated by cell-cell contact between appropriate pre- and
      postsynaptic cells and is followed by recruitment of protein complexes in both
      pre- and postsynaptic compartments. In this issue of Neuron, Lyles et al. show
      that in cultured Aplysia neurons, clustering of an mRNA at nascent synapses is
      not only induced by the recognition between synaptic partners, but is also
      required for further synaptic development and maintenance.

PMID- 16446135
TI  - "Runx"ing towards sensory differentiation.
AB  - Somatosensory stimuli are encoded by molecularly and anatomically diverse classes
      of dorsal root ganglia (DRG) neurons. In this issue of Neuron, three papers
      demonstrate that the Runx transcription factors, Runx1 and Runx3, respectively
      regulate the molecular identities and spinal terminations of TrkA+ nociceptive
      neurons and TrkC+ proprioceptive neurons. These findings emphasize the importance
      of intrinsic genetic programs in generating the diversity of DRG neurons and
      specifying the circuits into which they incorporate.

PMID- 16446136
TI  - A flashing line can warp your mind.
AB  - Keeping pace with a constantly changing world requires the ability to make
      predictions about the future on a variety of timescales. A very basic example of
      this is the ability to predict the future location of a moving object in the
      brief time that it takes to perceive and respond to that object. In this issue of
      Neuron, experiments by Sundberg, Fallah, and Reynolds reveal a potential neural
      substrate for making short-range predictions about motion in visual area V4.

PMID- 16446137
TI  - Melanopsin: another way of signaling light.
AB  - A subset of melanopsin-expressing retinal ganglion cells has been identified to
      be directly photosensitive (pRGCs), modulating a range of behavioral and
      physiological responses to light. Recent expression studies of melanopsin have
      provided compelling evidence that melanopsin is the photopigment of the pRGCs.
      However, the mechanism by which melanopsin transduces light information remains
      an open question. This review discusses the signaling pathways that may underlie
      melanopsin-dependent phototransduction in native pRGCs, as well as the many
      exciting challenges ahead.

PMID- 16446138
TI  - The disease progression of Mecp2 mutant mice is affected by the level of BDNF
      expression.
AB  - Mutations in the MECP2 gene cause Rett syndrome (RTT). Bdnf is a MeCP2 target
      gene; however, its role in RTT pathogenesis is unknown. We examined Bdnf
      conditional mutant mice for RTT-relevant pathologies and observed that loss of
      BDNF caused smaller brain size, smaller CA2 neurons, smaller glomerulus size, and
      a characteristic hindlimb-clasping phenotype. BDNF protein level was reduced in
      Mecp2 mutant mice, and deletion of Bdnf in Mecp2 mutants caused an earlier onset
      of RTT-like symptoms. To assess whether this interaction was functional and
      potentially therapeutically relevant, we increased BDNF expression in the Mecp2
      mutant brain with a conditional Bdnf transgene. BDNF overexpression extended the
      lifespan, rescued a locomotor defect, and reversed an electrophysiological
      deficit observed in Mecp2 mutants. Our results provide in vivo evidence for a
      functional interaction between Mecp2 and Bdnf and demonstrate the physiological
      significance of altered BDNF expression/signaling in RTT disease progression.

PMID- 16446139
TI  - Synapse formation and mRNA localization in cultured Aplysia neurons.
AB  - mRNA localization and regulated translation provide a means of spatially
      restricting gene expression within neurons during axon guidance and long-term
      synaptic plasticity. Here we show that synapse formation specifically alters the
      localization of the mRNA encoding sensorin, a peptide neurotransmitter with
      neurotrophin-like properties. In isolated Aplysia sensory neurons, which do not
      form chemical synapses, sensorin mRNA is diffusely distributed throughout distal
      neurites. Upon contact with a target motor neuron, sensorin mRNA rapidly
      concentrates at synapses. This redistribution only occurs in the presence of a
      target motor neuron and parallels the distribution of sensorin protein. Reduction
      of sensorin mRNA, but not protein, with dsRNA inhibits synapse formation. Our
      results indicate that synapse formation can alter mRNA localization within
      individual neurons. They further suggest that translation of a specific localized
      mRNA, encoding the neuropeptide sensorin, is required for synapse formation
      between sensory and motor neurons.

PMID- 16446140
TI  - Strong single-fiber sensory inputs to olfactory cortex: implications for
      olfactory coding.
AB  - Olfactory information is first encoded in a combinatorial fashion by olfactory
      bulb glomeruli, which individually represent distinct chemical features of odors.
      This information is then transmitted to piriform (olfactory) cortex, via axons of
      olfactory bulb mitral and tufted (M/T) cells, where it is presumed to form the
      odor percept. However, mechanisms governing the integration of sensory
      information in mammalian olfactory cortex are unclear. Here we show that single
      M/T cells can make powerful connections with cortical pyramidal cells, and
      coincident input from few M/T cells is sufficient to elicit spike output. These
      findings suggest that odor coding is broad and distributed in olfactory cortex.

PMID- 16446141
TI  - Runx1 determines nociceptive sensory neuron phenotype and is required for thermal
      and neuropathic pain.
AB  - In mammals, the perception of pain is initiated by the transduction of noxious
      stimuli through specialized ion channels and receptors expressed by nociceptive
      sensory neurons. The molecular mechanisms responsible for the specification of
      distinct sensory modality are, however, largely unknown. We show here that Runx1,
      a Runt domain transcription factor, is expressed in most nociceptors during
      embryonic development but in adult mice, becomes restricted to nociceptors marked
      by expression of the neurotrophin receptor Ret. In these neurons, Runx1 regulates
      the expression of many ion channels and receptors, including TRP class thermal
      receptors, Na+-gated, ATP-gated, and H+-gated channels, the opioid receptor MOR,
      and Mrgpr class G protein coupled receptors. Runx1 also controls the lamina
      specific innervation pattern of nociceptive afferents in the spinal cord.
      Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic
      pain. Thus, Runx1 coordinates the phenotype of a large cohort of nociceptors, a
      finding with implications for pain therapy.

PMID- 16446142
TI  - A role for Runx transcription factor signaling in dorsal root ganglion sensory
      neuron diversification.
AB  - Subpopulations of sensory neurons in the dorsal root ganglion (DRG) can be
      characterized on the basis of sensory modalities that convey distinct peripheral
      stimuli, but the molecular mechanisms that underlie sensory neuronal
      diversification remain unclear. Here, we have used genetic manipulations in the
      mouse embryo to examine how Runx transcription factor signaling controls the
      acquisition of distinct DRG neuronal subtype identities. Runx3 acts to diversify
      an Ngn1-independent neuronal cohort by promoting the differentiation of
      proprioceptive sensory neurons through erosion of TrkB expression in prospective
      TrkC+ sensory neurons. In contrast, Runx1 controls neuronal diversification
      within Ngn1-dependent TrkA+ neurons by repression of neuropeptide CGRP expression
      and controlling the fine pattern of laminar termination in the dorsal spinal
      cord. Together, our findings suggest that Runx transcription factor signaling
      plays a key role in sensory neuron diversification.

PMID- 16446143
TI  - Graded activity of transcription factor Runx3 specifies the laminar termination
      pattern of sensory axons in the developing spinal cord.
AB  - Different functional classes of dorsal root ganglion sensory neurons project
      their axons to distinct target zones within the developing spinal cord. To
      explore the mechanisms that link sensory neuron subtype identity and axonal
      projection pattern, we analyzed the roles of Runx and ETS transcription factors
      in the laminar targeting of sensory afferents. Gain- and loss-of-function studies
      in chick embryos reveal that the status of Runx3 expression is a major
      determinant of the dorso-ventral position of termination of proprioceptive and
      cutaneous sensory axons. In addition, the level of expression and/or activity of
      Runx3 in individual proprioceptive sensory neurons appears to specify whether
      their axons terminate in intermediate or ventral regions. Our findings suggest
      that the selectivity of Runx3 expression, and its level of activity, control
      sensory afferent targeting in the developing spinal cord.

PMID- 16446144
TI  - Neuromodulation of Na+ channel slow inactivation via cAMP-dependent protein
      kinase and protein kinase C.
AB  - Neurotransmitters modulate sodium channel availability through activation of G
      protein-coupled receptors, cAMP-dependent protein kinase (PKA), and protein
      kinase C (PKC). Voltage-dependent slow inactivation also controls sodium channel
      availability, synaptic integration, and neuronal firing. Here we show by analysis
      of sodium channel mutants that neuromodulation via PKA and PKC enhances intrinsic
      slow inactivation of sodium channels, making them unavailable for activation.
      Mutations in the S6 segment in domain III (N1466A,D) either enhance or block slow
      inactivation, implicating S6 segments in the molecular pathway for slow
      inactivation. Modulation of N1466A channels by PKC or PKA is increased, whereas
      modulation of N1466D is nearly completely blocked. These results demonstrate that
      neuromodulation by PKA and PKC is caused by their enhancement of intrinsic slow
      inactivation gating. Modulation of slow inactivation by neurotransmitters acting
      through G protein-coupled receptors, PKA, and PKC is a flexible mechanism of
      cellular plasticity controlling the firing behavior of central neurons.

PMID- 16446145
TI  - Thalamic burst mode and inattention in the awake LGNd.
AB  - Awake mammals are often inattentive in familiar environments, but must still
      respond appropriately to relevant visual stimulation. Such "inattentive vision"
      has received little study, perhaps due to difficulties in controlling eye
      position in this state. In rabbits, eye position is exceedingly stable in both
      alert and inattentive states. Here, we exploit this stability to examine temporal
      filtering of visual information in LGNd neurons as rabbits alternate between EEG
      defined states. Within a single second of shifting from alert to an inattentive
      state, both peak temporal frequency and bandwidth were sharply reduced, and burst
      frequency increased dramatically. However, spatial dimensions of receptive field
      centers showed no significant state dependence. We conclude that extremely rapid
      and significant changes in temporal filtering and bursting occur in the LGNd as
      awake subjects shift between alert and inattentive states.

PMID- 16446146
TI  - Object selectivity of local field potentials and spikes in the macaque inferior
      temporal cortex.
AB  - Local field potentials (LFPs) arise largely from dendritic activity over large
      brain regions and thus provide a measure of the input to and local processing
      within an area. We characterized LFPs and their relationship to spikes (multi and
      single unit) in monkey inferior temporal cortex (IT). LFP responses in IT to
      complex objects showed strong selectivity at 44% of the sites and tolerance to
      retinal position and size. The LFP preferences were poorly predicted by the spike
      preferences at the same site but were better explained by averaging spikes within
      approximately 3 mm. A comparison of separate sites suggests that selectivity is
      similar on a scale of approximately 800 microm for spikes and approximately 5 mm
      for LFPs. These observations imply that inputs to IT neurons convey selectivity
      for complex shapes and that such input may have an underlying organization
      spanning several millimeters.

PMID- 16446147
TI  - A motion-dependent distortion of retinotopy in area V4.
AB  - When one element in an apparent motion sequence differs in color from the others,
      it is perceived as shifted along the motion trajectory. We examined whether V4
      neurons encode the physical or perceived location of this "flashed" element by
      recording neuronal responses while monkeys viewed these stimuli. The retinotopic
      locus of V4 activity evoked by the flashed element shifted along the motion
      trajectory. The magnitude of the shift is consistent with the perceptual shift in
      humans viewing identical stimuli. This retinotopic distortion depended on the
      presence of a flashed element but was observed for both color-selective and non
      color-selective neurons. The distortion was undiminished when the flashed element
      terminated the sequence, a condition that reduced the perceptual shift in humans.
      These findings are consistent with a Bayesian model of localization in which
      perceived location is derived from position signals optimally integrated across
      visual areas.

PMID- 16446148
TI  - The hippocampus supports both the recollection and the familiarity components of
      recognition memory.
AB  - The receiver operating characteristic (ROC) has been used to investigate the
      component processes of recognition memory. Some studies with this technique have
      been taken to indicate that the hippocampus selectively supports the process of
      recollection, whereas adjacent cortex in the parahippocampal gyrus supports the
      process of familiarity. We analyzed ROC data from young adults, memory-impaired
      patients with limited hippocampal lesions, and age-matched controls. The shape of
      the ROC changed in similar ways from asymmetric to symmetric, as a function of
      the strength of memory (strong to weak) in both the young adults and the
      patients. Moreover, once overall memory strength was similar, the shape of the
      patient ROC was asymmetric and matched the control ROC. These results suggest
      that the component processes that determine the shape of the ROC are operative in
      the absence of the hippocampus, and they argue against the idea that the
      hippocampus selectively supports the recollection process.

PMID- 16446150
TI  - Solving the puzzle of deliberate self-harm: the experiential avoidance model.
AB  - Despite increasing attention to the phenomenon of deliberate self-harm (DSH), the
      literature currently lacks a unifying, evidence-based, theoretical framework
      within which to understand the factors that control this behavior. The purpose of
      the present paper is to outline such a framework-the Experiential Avoidance Model
      (EAM) of DSH. The EAM poses that DSH is primarily maintained by negative
      reinforcement in the form of escape from, or avoidance of, unwanted emotional
      experiences. Literature on factors that may lead to experiential avoidance is
      reviewed, along with the mounting empirical evidence that DSH functions to help
      the individual escape from unwanted emotional experiences. The EAM integrates a
      variety of research on emotions, experiential avoidance, and DSH within a
      clinically useful framework that sparks novel research directions.

PMID- 16446149
TI  - Dissociable codes of odor quality and odorant structure in human piriform cortex.
AB  - The relationship between odorant structure and odor quality has been a focus of
      olfactory research for 100 years, although no systematic correlations are yet
      apparent. Animal studies suggest that topographical representations of odorant
      structure in olfactory bulb form the perceptual basis of odor quality. Whether
      central olfactory regions are similarly organized is unclear. Using an olfactory
      version of fMRI cross-adaptation, we measured neural responses in primary
      olfactory (piriform) cortex as subjects smelled pairs of odorants systematically
      differing in quality and molecular functional group (as one critical attribute of
      odorant structure). Our results indicate a double dissociation in piriform
      cortex, whereby posterior regions encode quality (but not structure) and anterior
      regions encode structure (but not quality). The presence of structure-based codes
      suggests fidelity of sensory information arising from olfactory bulb. In turn,
      quality-based codes are independent of any simple structural configuration,
      implying that synthetic mechanisms may underlie our experience of smell.

PMID- 16446151
TI  - Anhedonia and emotional numbing in combat veterans with PTSD.
AB  - We explored relationships between anhedonia and posttraumatic stress disorder
      (PTSD) symptom clusters, including their role in predicting psychiatric
      comorbidity. Our measure of anhedonia was derived from an examination of the
      latent structure of the Beck Depression Inventory. We found evidence for a two
      factor solution, leading to anhedonia and undifferentiated, global depressive
      symptoms scales. In primary analyses, anhedonia had a unique positive
      relationship with PTSD's emotional numbing symptoms and minimal relationships
      with other PTSD symptoms. Upon examining the incremental validity of appetitive
      functioning (i.e., anhedonia, emotional numbing) over and above aversive
      functioning (i.e., re-experiencing, avoidance, and hyper-arousal PTSD symptoms)
      variables, greater emotional numbing increased the likelihood of being diagnosed
      with a major depressive disorder, and greater anhedonia increased the likelihood
      of being diagnosed with additional anxiety disorders and to a lesser extent,
      psychotic disorders. Results were consistent with research on the distinction of
      appetitive and aversive functioning, providing insight into the nature of PTSD.

PMID- 16446152
TI  - Expansion and redifferentiation of adult human pancreatic islet cells.
AB  - Beta-cell replacement represents the ultimate cure for type 1 diabetes, however
      it is limited by availability of organ donors. Adult human islets are difficult
      to propagate in culture, and efforts to expand them result in dedifferentiation.
      Here we describe conditions for expansion of adult human islet cells, as well as
      a way for their redifferentiation. Most cells in islets isolated from human
      pancreata were induced to replicate within the first week of culture in expansion
      medium. Cells were propagated for 16 population doublings, without a change in
      replication rate or noticeable cell mortality, representing an expansion of over
      65,000-fold. Replication was accompanied by a decrease in expression of key beta
      cell genes. Shift of the cells to differentiation medium containing betacellulin
      resulted in redifferentiation, as manifested by restoration of beta-cell gene
      expression and insulin content. These methods may allow transplantation of
      functional islet cells from single donors into multiple recipients.

PMID- 16446153
TI  - Direct interaction of Bcl-2 proteins with tubulin.
AB  - A direct interaction between tubulin and several pro-apoptotic and anti-apoptotic
      members of the Bcl-2 family has been demonstrated by effects on the assembly of
      microtubules from pure rat brain tubulin. Bcl-2, Bid, and Bad inhibit assembly
      sub-stoichiometrically, whereas peptides from Bak and Bax promote tubulin
      polymerization at near stoichiometric concentrations. These opposite effects on
      microtubule assembly are mutually antagonistic. The BH3 homology domains, common
      to all members of the family, are involved in the interaction with tubulin but do
      not themselves affect polymerization. Pelleting experiments with paclitaxel
      stabilized microtubules show that Bak is associated with the microtubule pellet,
      whereas Bid remains primarily with the unpolymerized fraction. These interactions
      require the presence of the anionic C-termini of alpha- and beta-tubulin as they
      do not occur with tubulin S in which the C-termini have been removed. While in no
      way ruling out other pathways, such direct associations are the simplest
      potential regulatory mechanism for apoptosis resulting from disturbances in
      microtubule or tubulin function.

PMID- 16446154
TI  - Decreased mortality in a rat model of acute postinfarction heart failure.
AB  - INTRODUCTION: The rat model of postinfarction heart failure (HF) has been very
      valuable in experimental cardiology. One disadvantage of this model is the very
      high acute mortality (70-80%). The aim of this study was to evaluate whether
      measures of intensive cardiac care applied to rats with acute myocardial
      infarction (MI) would reduce mortality. METHODS: Male Sprague-Dawley rats
      weighing approximately 300 g were used. The animals were randomized into two
      groups. The intensive care group (IC) n=20 and conventional care group (CC) n=20.
      Experimental MI was induced by ligation of the left coronary artery producing
      large anterolateral MI. Animals in the IC group received isoflurane anesthesia
      and respiratory support postoperatively. The heart rhythm was monitored
      continuously and ventricular arrhythmias were treated with amiodarone and
      cardioversion. RESULTS: Mortality rate within 24 h was 4/20 (20%) in the IC group
      and 14/20 (70%) in the CC group (p<0.01). This represents a 3.5-fold reduction in
      acute mortality rate. CONCLUSIONS: The use of amiodarone, respiratory support,
      isoflurane gas anesthesia, and electrical cardioversion of malignant arrhythmias
      are simple and effective measures to reduce mortality in rats with acute MI and
      HF. Improving survival rates increases cost-efficiency and ethical acceptance of
      this important experimental HF model.

PMID- 16446155
TI  - Erythromycin block of the HERG K+ channel: accessibility to F656 and Y652.
AB  - The HERG potassium channel might have a non-canonical drug binding site, distinct
      from the channel's inner cavity, that could be responsible for elements of closed
      state pharmacological inhibition of the channel. The macrolide antibiotic
      erythromycin is a drug that may block unconventionally because of its size. Here
      we used whole-cell patch-clamp recording at 37 degrees C from heterologously
      expressed HERG channels in a mammalian cell line to show that erythromycin either
      produces a rapid open-state-dependent HERG channel inhibition, or components of
      both open-state-dependent and closed-state-dependent inhibition. Alanine
      substitution of HERG's canonical determinants of blockade revealed that Y652 was
      not important as a molecular determinant of blockade, and that mutation of F656
      resulted in only weak attenuation of inhibition. In computer models of the
      channel, erythromycin could make several direct contacts with F656, but not with
      Y652, in the open-state model, and erythromycin was unable to fit into a closed
      state channel model.

PMID- 16446156
TI  - Opposite effects of alternative TZF spliced variants on androgen receptor.
AB  - We previously demonstrated that testicular zinc-finger protein (TZF) was a
      corepressor of the androgen receptor (AR). In the present study, we further
      showed that TZF-L, an alternative spliced variant of TZF, enhanced
      transactivation function of AR. Deletion analysis of TZF-L revealed that its N
      terminus, which almost corresponded to that of TZF, but not its C-terminus was
      able to interact with AR. Additional analysis suggested that TZF and TZF-L were
      able to form both homodimers and heterodimers. TZF-L inhibited the homodimer
      formation of TZF and the intranuclear dot formation of TZF. We propose that in
      the unique regulation system of AR-mediated transactivation, two spliced isoforms
      of TZF act as coactivator and corepressor, respectively.

PMID- 16446157
TI  - Comparison of computational algorithms applied on transthoracic impedance
      waveforms to predict head-up tilt table testing outcome.
AB  - The goal of the present study was to develop and evaluate new algorithms for the
      prediction of the outcome of a head-upright tilt test (HUTT). Using transthoracic
      impedance and its first derivative, we attempted to determine if indexes computed
      on these waveforms could detect a positive outcome to a 70 degrees -45min HUTT
      with reliable sensitivity and specificity. The methods were evaluated
      retrospectively in a group of 70 patients and validated prospectively in a group
      of 59 patients. The best detector obtained used a neural network. It compares
      very favorably with published results for other syncope detectors.

PMID- 16446158
TI  - Fetal heart rate monitoring based on independent component analysis.
AB  - In this paper, an algorithm based on independent component analysis (ICA) for
      extracting the fetal heart rate (FHR) from maternal abdominal electrodes is
      presented. Three abdominal ECG channels are used to extract the FHR in three
      steps: first preprocessing procedures such as DC cancellation and low-pass
      filtering are applied to remove noise. Then the algorithm for multiple unknown
      source extraction (AMUSE) algorithm is fed to extract the sources from the
      observation signals include fetal ECG (FECG). Finally, FHR is extracted from
      FECG. The method is shown to be capable of completely revealing FECG R-peaks from
      observation leads even with a SNR=-200dB using semi-synthetic data.

PMID- 16446159
TI  - Independent component analysis for synthetic aperture magnetometry in
      magnetocardiography.
AB  - We propose independent component analysis (ICA) as a pre-process for synthetic
      aperture magnetometry (SAM) in magnetocardiogram. SAM is a very useful method for
      source current imaging. However, SAM cannot separate one source from the others
      when there are time-correlated multi-sources, especially for successively active
      sources. The proposed method compensates the intrinsic drawback of SAM with ICA,
      which is feasible for 3-D imaging of the myocardial current distribution of
      specific temporal features. By using our method, we successfully localized an
      accessory pathway of a patient suffering from the WPW syndrome.

PMID- 16446160
TI  - Using functional data analysis to summarise and interpret lactate curves.
AB  - John Tukey used the term exploratory data analysis (EDA) to describe a philosophy
      for analyzing data where graphical and numerical summaries are used to uncover
      interesting structures. The applied statistician today has a much more
      sophisticated set of methods to use when applying the EDA philosophy. One such
      collection of methods is functional data analysis (FDA), which was used to
      explore the structure of lactate curves. A principal components analysis and
      plots of the second derivatives provide new intuitive endurance markers which
      correlates highly with other numerical summaries of lactate curves that have been
      suggested in the literature.

PMID- 16446161
TI  - Detection of gastric dysrhythmia using WT and ANN in diabetic gastroparesis
      patients.
AB  - Gastric myoelectrical activity can be measured by a noninvasive technique called
      electrogastrography where surface electrodes are placed on the epigastric area of
      the abdomen. The electrogastrogram (EGG) signal is by nature a nonstationary
      signal in terms of its frequency, amplitude and wave shape. Unlike the other
      methods discrete wavelet analysis (DWT) was designed for nonstationary signals.
      For automatic assessment of EGG, we used artificial neural networks (ANNs) that
      have been widely employed in pattern recognition due to their great potential of
      high performance, flexibility, robust fault tolerance, cost-effective
      functionality and capability for real-time applications. So we developed a new
      method for classification of EGG based on DWT and ANN.

PMID- 16446162
TI  - Human electroencephalograms seen as fractal time series: mathematical analysis
      and visualization.
AB  - The paper presents a novel technique of nonlinear spectral analysis, which has
      been used for processing encephalograms of humans. This technique is based on the
      concept of generalized entropy of a given probability distribution, known as the
      Renyi entropy that allows defining the set of generalized fractal dimensions of
      encephalogram (EEG) and determining fractal spectra of encephalographic signals.
      Unlike the Fourier spectra, the spectra of fractal dimensions contain information
      of both frequency and amplitude characteristics of EEG and can be used together
      with well-accepted techniques of EEG analysis as an enhancement of the latter.
      Powered by volume visualization of the brain activity, the method provides new
      clues for understanding the mental processes in humans.

PMID- 16446163
TI  - Conditional volatility properties of sleep-disordered breathing.
AB  - The present paper investigates the conditional volatility properties of apneic
      electrocardiogram (ECG) sequences taken from the Physionet apnea database using a
      set of GARCH models. We discuss the theoretical justification of this approach in
      the light of the recent developments in heart rate volatility studies. The
      findings support the value of the Integrated GARCH(1,1) specification in fitting
      apneic ECG segments implying the presence of shocks to conditional volatility
      that persist over time. The ARCH(1) model was found superior in fitting normal
      ECG recordings. These findings provide an important indication to future research
      that GARCH models can be employed in the development of an apnea screening tool
      to be used in clinical settings.

PMID- 16446164
TI  - Degree prediction of malignancy in brain glioma using support vector machines.
AB  - The degree of malignancy in brain glioma needs to be assessed by MRI findings and
      clinical data before operations. There have been previous attempts to solve this
      problem with a fuzzy rule extraction algorithm based on fuzzy min-max neural
      networks. We utilize support vector machines with floating search method to
      select relevant features and to predict the degree of malignancy. Computation
      results show that the feature subset selected by our techniques can yield better
      classification performance. In contrast with the base line method, which
      generated two rules and obtained 83.21% accuracy on the whole data set, our
      method generates one rule to yield 88.21% accuracy.

PMID- 16446166
TI  - Complexity and function of cytokine responses in experimental infection by
      Echinococcus granulosus.
AB  - Cytokines are important in the regulation of the immune system and are secreted
      by a variety of cells in response to self and non-self stimuli. Communication
      within cells, in the same or distant anatomical sites, occurs via cytokines which
      determine the quality and intensity of inflammatory and adaptive immune
      responses. Infection by helminths is characterized by a dominant secretion of
      type-2 cytokines; IL-4, IL-5, IL-10 (among others), which down-regulates the
      induction and functions of type-1 cytokines. The molecular mechanisms involved in
      the polarization of type-2 responses and their biological significance in
      helminthic infections are unknown, and probably depends on each host-parasite
      system. Understanding these issues may contribute to immune therapy against
      parasitic infections. Here we summarize our data obtained in Echinococcus
      granulosus experimental infection regarding type-2 cytokine induction and its
      putative role in the host-parasite interaction. Results suggest that induction of
      cytokine responses at different stages of infection is complex and depends on
      several parameters. In addition, they support the hypothesis that early IL-10,
      secreted by B cells in response to non-proteic antigens, may favour parasite
      survival and the establishment of a polarized type-2 cytokine response.

PMID- 16446167
TI  - Naked DNA immunization as an approach to target the generic tumor antigen
      survivin induces humoral and cellular immune responses in mice.
AB  - Survivin, a 16.5 kDa tumor associated antigen, is the smallest member of the
      inhibitor of apoptosis family that is abundantly expressed during development but
      essentially absent in normal adult tissues. Interestingly, survivin expression is
      up-regulated in virtually all types of cancers studied, as well as in vascular
      endothelial cells during tumor associated angiogenesis. Survivin links apoptosis
      to cell cycle progression and plays a pivotal role in regulation of cell
      proliferation. These characteristics make survivin a potentially promising
      generic target for cancer immunotherapy. Hence, a genetic immunization strategy
      to induce tumor-specific immune responses against human survivin in a pre
      clinical animal model was developed. In initial studies, BALB/c mice were
      immunized by intramuscular injection with DNA coding for human survivin
      (pcDNA3.1/hSurv). In addition, a construct encoding a secreted version of
      survivin (pSecTag2B/hSurv) was designed. A plasmid coding for murine granulocyte
      macrophage colony-stimulating factor (GM-CSF) was co-injected in both cases as a
      molecular adjuvant. Expression of survivin following transfection in mouse cells
      was corroborated. Humoral responses against human survivin were detected in mice
      sera using two immunization protocols (injections at 2- or 3-week intervals). The
      humoral response was markedly improved by secretion of survivin and co-expression
      of GM-CSF. The predominant antibody subclass detected in responsive mice was
      IgG2a, suggesting that a Th1-CD4+ cellular response had been induced.
      Furthermore, DNA immunization with survivin encoding vectors generated an
      effective CD8+ T cell response measured as an increase of cytotoxic Interferon
      gamma (IFN-gamma) secreting CD8+ T cells. In conclusion, intramuscular genetic
      immunization of mice with human survivin encoding plasmids induced a survivin
      specific humoral as well as cellular immune response in recipient mice. Secretion
      of survivin and co-injection of GM-CSF as a genetic adjuvant appear to be more
      important in generating an humoral than a cellular immune response.

PMID- 16446168
TI  - Immunization with antigen-pulsed dendritic cells significantly improves the
      immune response to weak self-antigens.
AB  - Dendritic cells (DCs) are the only professional antigen-presenting cells endowed
      with the ability to stimulate naive T cells and initiate a primary immune
      response. For this reason, DC-based immunization has been shown to be highly
      effective in eliciting CTL responses to viruses and tumor-associated antigens.
      Here we report on the use of DC immunization to enhance the B cell-mediated
      humoral immune response to highly conserved proteins and the application of this
      approach to the generation of monoclonal antibodies (mAbs) against these
      proteins. To illustrate the technique we describe the production of mAbs to class
      II transactivator (CIITA), the major histocompatibility complex (MHC) CIITA, a
      difficult immunogen owing to its high degree of identity among species. We show
      that mice immunized with a combination of an intravenous injection of DCs pulsed
      with recombinant fragments of CIITA followed by intraperitoneal injection of the
      antigen in incomplete Freund's adjuvant induced a detectable antibody response
      against CIITA, while sera from mice immunized using the traditional method (i.e.
      intraperitoneal immunization with 50mug of protein in complete Freund's adjuvant)
      gave an almost undetectable response. Furthermore, a total of four fusion
      experiments demonstrate that immunization with Ag-pulsed DCs is necessary for the
      efficient generation of hybridomas and a good yield of mAbs specific for the
      recombinant and the native endogenous CIITA protein. Conversely, four independent
      fusions carried out with splenocytes from mice immunized using the traditional
      method failed to produce anti-CIITA hybridomas. We propose that immunization with
      antigen-loaded DCs should be the method of preference when attempting to raise
      mAbs against weak self-immunogens.

PMID- 16446169
TI  - Neutrophils regulate the expression of cytokines, chemokines and nitric oxide
      synthase/nitric oxide in mice injected with Bothrops atrox venom.
AB  - Bothrops atrox crude venom injected intraperitoneal (i.p.) into BALB/c mice
      induced local afflux of inflammatory cells, one neutrophil-rich peak after 6h and
      another macrophage-rich peak after 48 h. A similar pattern of local cell afflux
      plus edema, Delta lesions of some skeletal muscle cells, and hemorrhage were
      observed in mice intramuscular (i.m.) injected with the venom. Measurement of
      serum cytokines in neutrophil-depleted (by anti-mouse rat monoclonal antibody
      (mAb) RB6-8C5) and non-depleted BALB/c mice was performed by ELISA. With the
      exception of IL-1beta (78 pg/ml), higher levels of IL-6 (1348 pg/ml), MIP-1beta
      (437 pg/ml) and MIP-2 (904 pg/ml) were observed in neutrophil-depleted mice, in
      comparison to the values found in non-neutrophil depleted mice: IL-1beta (437
      pg/ml), IL-6 (750 pg/ml), MIP-1beta (165 pg/ml) and MIP-2 (90 pg/ml). TNF-alpha
      was not detected. NO was detected (18 microM) 24h after venom injection in
      neutrophil-depleted mice. RT-PCR using representative primers detected expression
      of mRNA in cells from BALB/c mice injected with B. atrox venom: (a) for IL-1beta,
      IL-6, inducible nitric oxide synthase (iNOS), CXCR2, MIP-2 and RANTES in cells
      from mice that were neutrophil-depleted or not; (b) for CCR1, CCR5 and MIP-1beta
      in cells from neutrophil-depleted mice; (c) for MIP-1alpha in cells from non
      neutrophil-depleted mice; (d) TNF-alpha and TGF-beta were not detected in either
      of the mice. These results indicate that neutrophils play a role in regulating
      the production of some cytokines and chemokines as well as locally expressed or
      liberated iNOS/NO in tissues injected with B. atrox crude venom.

PMID- 16446170
TI  - Modulation of T cell function by TCR/pMHC binding kinetics.
AB  - The interaction between the T cell receptor (TCR) and the peptide-MHC complex
      (pMHC) at the interface between the T cell and the antigen presenting cell (APC)
      is the main event controlling the specificity of antigen recognition by T cells.
      It is thought that TCR/pMHC binding kinetics are critical for the selection of
      the T cell repertoire in the thymus, as well as the activation of mature T cells
      in the periphery. One of the binding parameters that conditions T cell activation
      by pMHC ligands is the half-life of the TCR/pMHC interaction. This kinetic
      parameter is highly significant for the regulation of T cell activation and
      therefore determines the capacity of T cells to respond against pathogen- and
      tumor-derived antigens, avoiding self-reactivity. Several studies support the
      notion that T cells are activated only by TCR/pMHC interactions that are above a
      threshold of half-life. pMHC complexes that bind TCRs with half-lives below that
      threshold behave as null or antagonistic ligands. However, since prolonged half
      lives can also impair T cell activation, there seems to be a ceiling for the
      TCR/pMHC half life that leads to efficient activation of T cells. According to
      these observations, efficient T cell activation would require an optimal half
      life of TCR/pMHC interaction. These kinetic restrictions for T cell activation
      are important to generate a protective adaptive immune response minimizing cross
      reactivity against self-constituents. The nature of the TCR/pMHC interaction
      defines in the thymus whether a thymocyte develops into a mature T cell or is
      eliminated by apoptosis. In addition, the kinetics of TCR/pMHC binding can
      determine the type of response shown by mature T cells in the periphery. Although
      several studies have focused on the modulation of T cell function by the affinity
      of the TCR/pMHC interaction, the binding kinetics rules governing T cell
      activation remain poorly understood. Here we review recent data and propose a new
      model for the regulation of T cell function by TCR/pMHC binding kinetics.

PMID- 16446171
TI  - Evaluation of Brucella abortus DNA vaccine by expression of Cu-Zn superoxide
      dismutase antigen fused to IL-2.
AB  - The Cu-Zn superoxide dismutase (SOD) antigen of Brucella abortus was previously
      identified to be a T cell antigen which induces both proliferation of and gamma
      interferon (IFN-gamma) secretion by T cells from infected mice. In an earlier
      study, we demonstrated that intramuscular injection of mice with a plasmid DNA
      carrying the gene for SOD leads to the development of significant protection
      against B. abortus challenge. It has been reported that the antigen-specific
      immune responses generated by a DNA vaccine can be enhanced by co-delivery of
      certain cytokine genes. In this study, we evaluated the effect of delivering IL-2
      on the efficacy of SOD DNA vaccine by generating a plasmid (pSecTag-SOD-IL2) that
      codes for a secretory fusion protein of SOD and IL-2. Another plasmid (pSecTag
      SOD) that codes for only SOD as a secretory protein was used for comparison.
      BALB/c mice injected intramuscularly with pSecTag-SOD or pSecTag-SOD-IL2, but not
      the control plasmid pSecTag, developed SOD-specific antibody and T cell immune
      responses. Upon in vitro stimulation with recombinant SOD (rSOD) antigen, T cells
      from mice immunized with pSecTag-SOD-IL2, in comparison with those from mice
      immunized with pSecTag-SOD, exhibited a lower proliferation response but produced
      significantly higher concentrations of IFN-gamma. Both DNA vaccines, however,
      induced similar levels of SOD-specific antibodies and cytotoxic T cell response.
      Although mice immunized with pSecTag-SOD-IL2 showed increased resistance to
      challenge with B. abortus virulent strain 2308, this increase was not
      statistically significant from that of pSecTag-SOD vaccinated mice. These results
      suggest that a SOD DNA vaccine fused to IL2 did not improve protection efficacy.

PMID- 16446172
TI  - Could single-nucleotide polymorphisms (SNPs) affecting the tumour necrosis factor
      promoter be considered as part of rheumatoid arthritis evolution?
AB  - Tumour necrosis factor (TNF), a cytokine mainly produced by macrophages, is
      associated with a broad spectrum of biological effects, mainly associated with
      the host defense against microbes. The TNF gene is located on chromosome six
      within the major histocompatibility complex (MHC). Rheumatoid arthritis (RA) is a
      systemic autoimmune disease where TNF plays a central role in its etiology and
      pathogenesis. Written medical evidence of RA can be traced at least as far back
      as the 17th century, while human paleopathological studies appear to show the
      presence of RA prior to this period. The fact that RA has experienced an
      increment both in severity and mortality could be explained by many causes,
      particularly the crucial role of the immune system. Single-nucleotide
      polymorphisms (SNPs) are the most common genetic variations and occur at a
      frequency of approximately 1 in 1000 bp throughout the genome. The -308 TNF SNP
      is a mutation that affects the promoter region of the TNF gene. It defines the
      TNF1 and TNF2 alleles, determining low and high levels of TNF expression,
      respectively. The presence of the TNF2 allele has also been linked to increased
      susceptibility to and severity in a variety of autoimmune and inflammatory
      disorders, including RA, systemic lupus erythematosus, and ankylosing
      spondylitis. Studies on the functional significance of -308 SNP have detected
      higher levels of TNF production by cells from TNF2-carrying individuals than
      cells from TNF1 individuals. This difference does not appear to be due to other
      genes lying within the MHC region. Since the presence of the TNF2 allele may
      increase the host's resistance to local infection, by increasing local production
      of TNF at the infection site, we may suggest that such a mutation has emerged as
      a selective advantage to carriers of the TNF2 allele. This hypothesis may prove
      itself by observing the high incidence of tuberculosis and other infectious
      processes in those patients treated with anti-TNF therapy. Since the human
      lifespan has increased, the persistence of the TNF2 allele at high frequency in
      the population now confers what appears to be a marked survival disadvantage. As
      a result of the disregulation of the immune system, the genetically-predisposed
      host expresses larger amounts of TNF, leading to chronic inflammatory processes
      and autoimmune diseases, currently more prevalent. We suggest that RA, a
      relatively new and increasingly frequent disease, is favored by the presence of
      the -308 TNF promoter polymorphism, responsible for increased TNF production.

PMID- 16446173
TI  - Glucocorticoid receptor beta in acute and chronic inflammatory conditions:
      clinical implications.
AB  - Glucocorticoids (GC) are hormones with a wide variety of actions, including
      profound anti-inflammatory/immunosuppressive effects. Their actions are mediated
      by an intracellular receptor called the glucocorticoid receptor (GCR). The
      classical GCR that mediates the hormone response is called GCR alpha. Recently
      however, many GCR isotypes have been described. A defective GC action has been
      proposed as an etio-pathogenic mechanism for the development of
      inflammatory/autoimmune diseases. Inadequate GC actions may have multiple causes
      such as: defective hypothalamic-pituitary-adrenal axis function, GC export from
      cells, hormone metabolization into inactive compounds and modifications of the GC
      receptor, among others. In 1995, a dominant negative effect of a GC receptor
      isotype termed beta was described; starting a still unsolved controversy about
      the role of GCR beta as an inducer of GC resistance in certain pathological
      conditions. The present article will review the data about a possible role for
      GCR beta in the development of GC resistance in inflammatory diseases. This
      review will especially focus on the role of the GCR beta in rheumatoid arthritis
      and in septic shock as examples of a chronic inflammatory disease and an acute
      systemic inflammatory condition. Original data supporting possible
      hyperexpression of GCR beta in both conditions will be shown.

PMID- 16446174
TI  - Immunization with Schistosoma mansoni 22.6 kDa antigen induces partial protection
      against experimental infection in a recombinant protein form but not as DNA
      vaccine.
AB  - Schistosomiasis is a major public health problem that affects mainly developing
      countries. There are 200 million people worldwide infected with schistosomes
      resulting in more than 250,000 deaths per year. Although schistosomicidal drugs
      exist, the advent of an efficacious vaccine remains the most potentially powerful
      means for controlling this disease. In this study we isolated a cDNA clone
      encoding the Schistosoma mansoni lung-stage Sm22.6 protein, which is 100% and 79%
      identical with the 22.6 kDa adult worm tegument antigen of S. mansoni and S.
      japonicum, respectively. Further, we produced recombinant (r) Sm22.6 and
      constructed an Sm22.6 DNA vaccine. Western blot analysis confirmed the identity
      of purified MBP-Sm22.6 fusion protein using anti-MBP (maltose binding protein)
      and anti-rSm22.6 antibodies. Additionally, C57BL/6 mice were immunized and
      specific anti-Sm22.6 IgG responses were produced when both vaccination strategies
      were used. Importantly, only rSm22.6 vaccine provided levels of protection
      against challenge infection (34.5%). Mice immunized with rSm22.6 induced
      production of IgG1 and IgG2a and synthesis of IFN-gamma and IL-4 in cultured
      mouse splenocytes. Finally, rSm22.6 vaccination induced a Th0 type of immune
      response and protective immunity that suggests Sm22.6 as a potential candidate to
      compose an anti-schistosome vaccine.

PMID- 16446175
TI  - In vivo and in vitro effect of killed Propionibacterium acnes and its purified
      soluble polysaccharide on mouse bone marrow stem cells and dendritic cell
      differentiation.
AB  - Among the effects exerted by Propionibacterium acnes, a most relevant one is its
      capacity to modulate the Th1/Th2 cellular immune response. This effect depends on
      the induction and activation of antigen presenting cells, mainly dendritic cells
      (DCs), whose number is increased in the peripheral blood of animals treated with
      this bacterium. A soluble P. acnes polysaccharide (PS) extract also acts on DCs,
      modulating a Th1 immune response. These data led us to investigate the role of P.
      acnes and its soluble PS on murine bone marrow (BM) DCs. Bone marrow cells were
      analyzed by flow cytometry, showing an increase of stem cells and DCs in P. acnes
      or PS-treated animals. Culturing in the presence of granulocyte monocyte colony
      stimulating factor (GM-CSF) increased the in vitro differentiation and maturation
      of these cells into BM-derived DCs (CD11c+ and MHC class II+). Maturation of DCs
      was determined by increased CD80 and CD86 expression, IL-4 and IL-12 production,
      reduction in phagocytic capacity and increase in the antigen presenting ability
      to primed or naive T lymphocytes. These data indicate that P. acnes as well as
      its PS can modulate BM stem cells, originating mature DCs, which are important
      mainly at the initial antigen contact.

PMID- 16446176
TI  - Parasite cysteine proteinase interactions with alpha 2-macroglobulin or
      kininogens: differential pathways modulating inflammation and innate immunity in
      infection by pathogenic trypanosomatids.
AB  - Plasma extravasation is a common endothelium response to tissue injury provoked
      by pathogens. Herein I will review studies showing that host proteinase
      inhibitors (e.g., alpha2-macroglobulin (alpha2M) or kininogens) interact with
      protozoan cysteine proteinases (CPs) in extravascular infection sites, linking
      inflammation to innate immunity by different mechanisms. Using human monocytes as
      antigen presenting cells, we first demonstrated that alpha2M entrapment of
      cruzipain, a Trypanosoma cruzi CP, reduced the activation threshold of cruzipain
      specific CD4 T cells due to facilitated uptake of alpha2M-cruzipain complexes by
      the multiscavenger receptor (CD91). More recently, studies of the mechanisms
      underlying inflammation elicited by T. cruzi revealed that kininogens, once bound
      to glycosaminoglycans, are not able to efficiently inactivate cruzipain via their
      inhibitory cystatin-like domains. Instead, we found that cruzipain readily
      processes surface-bound kininogens, liberating bioactive kinins. Acting as
      paracrine hormones, kinins vigorously activate host cells through bradykinin (BK)
      receptors, thus stimulating endocytic uptake of the pathogen. Rather than
      unilaterally enhancing parasite infectivity, the liberated kinins activate innate
      immunity by potently stimulating dendritic cell maturation via the BK B2
      receptor. The discovery of chagasin, a novel family of endogenous inhibitors
      expressed by trypanosomatids, is likely another regulatory player involved in the
      dynamics of the inflammatory response.

PMID- 16446177
TI  - The role of regulatory T lymphocytes in the induced immune response mediated by
      biological vaccines.
AB  - Immunotherapy has become a novel therapeutic alternative for various kinds of
      tumours. Recently, we have finalized the first phase I clinical study in Chile
      for the treatment of advanced malignant melanoma, using dendritic cells (DCs)
      loaded with allogeneic melanoma cell lysate. This study included 20 patients and
      the obtained results, pioneer in Latin America, showed that DC-based
      immunotherapy is innocuous, even provided in combination with IL-2. In addition,
      immunological responses were detected in 50% of the treated patients,
      establishing a positive correlation between the delayed type hypersensitivity
      (DTH) reaction, which indicates induction of in vivo immunological memory, and
      patients surviving. Nevertheless, objective clinical responses in vaccinated
      patients are still insufficient. Only sporadic objective metastasis regressions
      have been registered and an important proportion of the treated patients did not
      respond, or their responses were weak. Several strategies have been described to
      be used by tumours to escape from the immune response. Actually, we have
      demonstrated that IL-10 inhibits antigen presentation in melanoma, reducing
      tumour sensitivity to melanoma-specific cytotoxic T lymphocytes (CTLs).
      Regulation of the immunological response by inhibitory cells could be another
      possible cause of clinical unresponsiveness. Lately, the existence of
      subpopulations of regulatory T lymphocytes (RTL) able to limit the immune
      response in a specific form has been established, specially inhibiting the
      proliferation and activity of CD4+ and CD8+ effector T lymphocytes. These
      cellular subpopulations, mostly CD4+/CD25+/Foxp3+ T lymphocytes (Treg) of thymic
      origin, or TR1 lymphocytes able to release IL-10, and tumour growth factor beta
      (TGF-beta) producing TH3 lymphocytes, would be accumulated in the body during
      tumour growth, inhibiting the immune response. In relation to RTL and cancer,
      evidence indicates that Treg cell numbers are increased in blood and other
      tissues in different types of cancer. Additionally, it has been demonstrated that
      in patients with refractory metastatic melanoma, the adoptive transference of
      anti-tumour CD8+ T lymphocytes after non-myeloablative chemotherapy was able to
      induce important tumour regressions that would be due to elimination of RTL
      populations. Additionally, chemotherapeutical drugs like decarbazine, besides
      their effect on tumour proliferation, also have an immunosuppressive effect on T
      lymphocyte populations, as well as on accumulated RTL. In this article, a novel
      strategy for the study of RTL is proposed, including potential therapeutic
      innovations, which is being pioneered in current clinical trials.

PMID- 16446178
TI  - An evaluation of information available on the internet regarding minimally
      invasive hip arthroplasty.
AB  - The Internet is a popular source of information regarding health care especially
      when seeking advice on new and less invasive surgical techniques. We evaluated
      150 Web sites (3 search engines) for authorship and quality of information
      regarding minimally invasive hip arthroplasty. The results revealed that 45% were
      authored by a hospital/university, 26% were news stories, 25% were private
      medical groups, and 6% were orthopedic industry Web sites. Forty-five percent
      offered the opportunity to make an appointment, 41% described the surgical
      technique, and only 15% explained eligibility. Thirteen percent described the
      risks, whereas 9% made reference to peer-reviewed publications. More than 91%
      made specific claims regarding the advantages of minimally invasive surgery. Our
      study suggests the information on the Internet regarding minimally invasive total
      hip arthroplasty is misleading and of poor quality.

PMID- 16446180
TI  - Lateral unicompartmental knee arthroplasty: survivorship and technical
      considerations at an average follow-up of 12.4 years.
AB  - Successful medial unicompartmental knee arthroplasty is becoming standard;
      however, the "screw-home" mechanism, internal femoral rotation on a fixed tibia
      as the knee is fully extended, should be taken into account with lateral
      compartment arthroplasty. Twenty-nine consecutive lateral unicompartmental
      arthroplasties were performed with our unique tibial component positioning in 10
      degrees to 15 degrees of internal rotation to compensate for the "screw-home"
      mechanism. The Hospital for Special Surgery knee score and serial radiographs
      were used in the evaluation of each patient. The mean duration of follow-up was
      12.4 years with no revisions. The HSS score was excellent or good in all knees.
      The average postoperative femoral-tibial alignment was 5 degrees of valgus, and
      the average posterior tibial slope was 6 degrees . Lateral unicompartmental
      arthroplasty can provide excellent long-term results with modified positioning of
      the tibial component.

PMID- 16446181
TI  - The practical limitations of resurfacing hip arthroplasty.
AB  - Resurfacing hip arthroplasty has recently experienced a resurgence in popularity,
      associated with an unprecedented amount of coverage in the media. This article
      assesses what proportion of a consecutive series of young adults presenting for
      total hip arthroplasty would have been suitable for resurfacing arthroplasty.
      Retrospective review of the preoperative radiographs was performed, with
      templating for the resurfacing prostheses. The hips were divided into those
      appropriate and those inappropriate for the procedure, and those in whom the
      procedure would be technically challenging. Sixty-one hips in 57 patients were
      reviewed, with ages ranging from 17 to 49 years. Twenty-eight hips were assessed
      as suitable, 26 as unsuitable, and 7 as technically challenging. Reasons for
      unsuitability included collapse and/or cystic degeneration of the femoral head.

PMID- 16446179
TI  - Mobility and perceived function after total knee arthroplasty.
AB  - Mobility using the timed up and go (TUG) and perceived pain, stiffness, and
      physical function (Western Ontario McMaster Universities Osteoarthritis Index)
      were documented after total knee arthroplasty (TKA). The relationships between
      mobility and perceived function are limited post-TKA. The first purpose of this
      study was to determine and compare the TUG test between individuals (n = 11) post
      TKA and age-sex-related controls (n = 11). The second purpose of this study was
      to explore the relationships between mobility and self-reported function post
      TKA. The TKA group was 28% (P < .05) slower in completing the TUG compared with
      controls and reported difficulty in attempting challenging tasks. The TUG was
      moderately related to the physical function (0.63) dimension of the Western
      Ontario and McMaster Universities Osteoarthritis Index, as well as the aggregate
      Western Ontario and McMaster Universities Osteoarthritis Index score (0.59).

PMID- 16446182
TI  - Perioperative autotransfusion in total hip and knee arthroplasty.
AB  - We assessed the OrthoPAT Orthopedic Perioperative Autotransfusion System (Zimmer
      Inc, Warsaw, Ind) in reducing the need for allogeneic blood in hip or knee
      arthroplasty. Patients (N = 398) were divided into 5 cohorts: unilateral primary
      hip (n = 131), unilateral revision hip (n = 38), unilateral primary knee (n =
      179), unilateral revision knee (n = 26), and bilateral primary knee (n = 24).
      Primary or revision hip arthroplasties with no preoperative autologous blood
      donation, knee arthroplasties with no preoperative autologous blood donation, and
      unilateral primary hip arthroplasties were 2.7, 2.3, and 2 times less likely (P <
      .05), respectively, to use allogeneic blood with OrthoPAT. We conclude that
      OrthoPAT use significantly reduced the risk of receiving allogeneic blood
      transfusions in defined patient subsets.

PMID- 16446184
TI  - Predictive risk factors for stiff knees in total knee arthroplasty.
AB  - Retrospective review of 1216 primary total knee arthroplasties (TKAs) to evaluate
      incidence and predictors of arthrofibrosis, defined as flexion less than 90
      degrees 1 year post-TKA. Incidence of stiffness post-TKA was 3.7% (45/1216). A
      matched case-control study was then conducted to identify predictive factors for
      this outcome. Preoperative flexion and intraoperative flexion were predictive of
      ultimate postoperative flexion (P = .001 and P = .039, respectively). There was
      no correlation between postoperative stiffness and specific medical
      comorbidities, including diabetes. Preoperative and postoperative relative
      decreased patellar height and stiffness postoperative were significantly
      correlated (P = .001). Although stiffness post-TKA is multifactorial, careful
      attention to surgical exposure, restoring gap kinematics, minimizing surgical
      trauma to the patellar ligament/extensor mechanism, appropriate implant
      selection, and physiotherapy combined with a well-motivated patient may all serve
      to reduce the incidence of stiffness post-TKA.

PMID- 16446185
TI  - Intramedullary total femoral replacement for salvage of the compromised femur
      associated with hip and knee arthroplasty.
AB  - Severely compromised femora because of prosthetic loosening, osteolysis, or
      periprosthetic fracture around total hip and knee arthroplasties are increasing.
      Two approaches that create an intramedullary total femoral (IMTF) replacement are
      reported. Twenty-three IMTF replacements in 22 patients were performed at 2
      institutions. Seven revision total knee arthroplasties with a stemmed component
      were linked to a well-fixed hip stem with a custom intramedullary sleeve. Sixteen
      IMTF replacements involved revision of both hip and knee arthroplasties which
      were connected via an intercalary segment with morse taper junctions. Follow-up
      averaged 36 months. Complications included 2 dislocations, 2 deep infections, and
      2 knee revisions for tibial loosening. Advantages over conventional total femoral
      replacement or ORIF include less dissection, maintenance of soft tissue
      attachments, and immediate component stability to allow for early mobilization.

PMID- 16446183
TI  - Flexibility in administration of fondaparinux for prevention of symptomatic
      venous thromboembolism in orthopaedic surgery.
AB  - Venous thromboembolism (VTE) is a common complication of total joint
      arthroplasty. Fondaparinux VTE prophylaxis is currently begun 6 to 8 hours after
      surgery. Flexible dosing may reduce bleeding risk and allow easier use by
      starting the morning after surgery instead of staggered hours on the surgery day.
      This study examined flexible timing of the first dose of fondaparinux. Whether
      the first dose was administered 8 +/- 2 hours after surgery or the morning after
      surgery, no significant difference was observed in incidence of symptomatic VTE
      (2.0% and 1.9%, respectively, P = .89). Major and minor bleeding events were
      similar between groups (1.2% and 0.7% [P = .19], and 1.4% and 2.0% [P = .31],
      respectively). Delaying initiation of fondaparinux prophylaxis provides an option
      after total joint arthroplasty with preserved efficacy and safety.

PMID- 16446186
TI  - Anterior trochanteric slide osteotomy for primary total hip arthroplasty. Review
      of nonunion and complications.
AB  - The radiographic results of 73 anterior trochanteric slide osteotomies were
      retrospectively reviewed at an average of 36 months after primary hip
      arthroplasty to determine the incidence of nonunion of the trochanter and
      complications related to trochanteric hardware. In each case, the trochanter was
      retracted anteriorly, with the gluteus medius and vastus lateralis muscle
      insertions left intact. Reattachment was performed with 2 monofilament wires or
      cables passed through the lesser trochanter in each case. Ninety-two percent of
      the trochanters healed; nonunion was associated with anterior displacement of the
      trochanteric fragment with external rotation of the femur. The incidence of
      repeat surgery for hardware-related problems was 28%. Although the slide
      osteotomy prevented proximal migration of the trochanteric fragment, the
      incidence of hardware complications was too high to justify the routine use of
      this approach in primary hip arthroplasty.

PMID- 16446187
TI  - The use of a hydroxyapatite-coated primary stem in revision total hip
      arthroplasty.
AB  - Proximal ingrowth of femoral components in total hip arthroplasty (THA) is
      desirable because it minimizes proximal stress shielding associated with distal
      ingrowth stems and maximizes bone stock. This is a retrospective evaluation of
      initial results of revision THA using a proximally hydroxyapatite-coated femoral
      stem nominally designed for primary use. Patients requiring femoral stem revision
      were included if they had sufficient femoral bone stock to support a proximally
      fixed prosthesis (n = 33). This represents 53% of the femoral revisions performed
      during the period of the study. The average follow-up was 5 years (range 48-88
      months). The mean Harris hip and Oxford hip scores were 86.5 and 25.2,
      respectively. Radiographically, 100% of the stems demonstrated bone ingrowth
      fixation. These results are superior to previous reports of primary cementless
      stems for revision THA. The use of a cementless nonmodular implant provides a
      viable option in some patients undergoing revision THA.

PMID- 16446188
TI  - Revision total hip arthroplasty for large medial (protrusio) defects with a rim
      fit cementless acetabular component.
AB  - Seventeen patients (19 hips) with protrusio acetabuli resulting from a failed
      total hip arthroplasty, large medial bone defect, and an intact bony rim were
      treated with an oversized cementless acetabular component and medial morcelized
      allograft. An average of 55% of the revision component was not supported by host
      bone. At an average follow-up of 2.8 (range 2-6) years, none of the acetabular
      components required revision for loosening. The average cup position
      preoperatively was 10.5 mm medial to Kohler's line and postoperatively was 6.8 mm
      lateral to Kohler's line. Despite very large medial defects, reconstructions with
      this technique remained stable.

PMID- 16446189
TI  - Uncemented rotating-platform total knee arthroplasty: a 4-year to 12-year follow
      up.
AB  - One hundred nine primary uncemented, rotating-platform, low-contact stress total
      knee arthroplasties in 85 patients were reviewed 4 to 12 years after the
      operation as a prospective study on consecutive cases. All patients were followed
      up annually with subjective questionnaires and radiological assessment. At the
      time of final review, 69 patients with 87 rotating-platform total knee
      arthroplasties were still alive. All were reviewed at the final follow-up using
      the American Knee Society Score (clinical and radiological). The average knee
      score was 86.42, and the average functional score was 65.1. No evidence of
      radiological loosening was observed in any patient. One knee was revised because
      of medial collateral ligament laxity. The 10-year survival rate was 99.08%.

PMID- 16446191
TI  - A prospective comparison of cement restrictor migration in primary total hip
      arthroplasty.
AB  - Pressurization techniques are used to improve the cement/bone interface at hip
      arthroplasty. Ultra-high-molecular-weight polyethylene (UHMWPE) cement
      restrictors leave particulate debris at insertion; biodegradable restrictors may
      therefore be preferable. We compared the migration behavior of 2 such cement
      restrictors. A prospective randomized study with 16 patients per group using
      either a UHMWPE or a biodegradable restrictor was performed. Comparison of
      intraoperative measurements and postoperative radiographs determined restrictor
      migration. Mean migration was 3.0 vs 0.5 cm (biodegradable vs UHMWPE, Mann
      Whitney U test, P < .002); median, 2.9 vs 0.4; SD, 1.8 vs 0.4; and range, 0.6 to
      6.4 vs 0 to 1.2. Our study found that the biodegradable restrictor allowed
      significantly more migration than the UHMWPE restrictor. Although there are
      theoretical advantages in avoiding UHMWPE restrictors, the current biodegradable
      alternative is actually inferior and its use cannot be endorsed.

PMID- 16446190
TI  - Failure of a "screw-in" acetabular component: ten-year results, survivorship
      analysis, and the prediction of failure.
AB  - The Rotalok screw-in threaded acetabular component was prospectively reviewed
      with 10-year clinical and radiological follow-up for 60 patients. Nine patients
      died and 5 were lost to follow-up. Clinically, 28 patients were pain-free, 13 had
      mild pain, and 3 had moderate pain. Thirteen patients underwent revision for
      loosening and 3 required revision but were unfit. Superior migration, angular
      migration, and zone lucency were measured radiologically. Cumulative survival was
      70.75% with revision surgery as the end point and 60% with combined clinical
      failure and revision as the end point. Angular migration of 3 degrees or more was
      a significant predictor of clinical failure and revision (P < .0001), with 5
      degrees being very highly predictive with a sensitivity of 0.72 and a specificity
      of 1.00. Revision was associated with younger patients (P = .03) and autograft
      use without screw stabilization (P = .024). The high failure rate of the Rotalok
      necessitates careful clinical and radiological follow-up, with asymptomatic
      radiological angular migration often the first predictor of failure.

PMID- 16446193
TI  - The relative cost of cemented and uncemented total hip arthroplasties.
AB  - The use of uncemented femoral stems in primary total hip arthroplasty (THA) has
      been slow to develop in the UK because of the lack of encouraging published long
      term follow-up data, the continued success of the cemented primary THA, and the
      perceived excessive relative cost of the uncemented THA. In this article, we
      argue that the total costs of 3 "proven" uncemented stems are comparable with
      commonly used cemented femoral components, when all necessary materials are taken
      into consideration. In addition, we will also discuss other potential benefits
      and drawbacks for considering the use of uncemented stems.

PMID- 16446194
TI  - Predictions on preserving bone mass in knee arthroplasty with bisphosphonates.
AB  - Using a computational model of bone adaptation, we investigated the long-term
      ability of bisphosphonates to minimize proximal bone loss that is associated with
      stress shielding in the tibia after long-stemmed total knee arthroplasty (TKA).
      When invoking bisphosphonate effects, the remodeling activity was suppressed, and
      the resorption size was reduced. Compared with the untreated simulation,
      bisphosphonate slowed the rate of bone loss after TKA (42% reduction in bone loss
      at 1 year). Activating the drug 3 months before the surgery reversed bone loss
      associated with the reduction in such activities as walking, but it did not
      provide any substantial benefit in the long-term. Late bisphosphonate treatment
      did not reverse the bone loss that occurred 3.5 years after TKA, although it
      preserved 3% of bone normally lost without treatment.

PMID- 16446192
TI  - Osteolysis of the greater trochanter: a result of bone anchors used for abductor
      reattachment at total hip arthroplasty.
AB  - Although bone anchors can help to repair soft tissues to bone, they are not
      without potential problems. A group of 214 consecutive total hip arthroplasties
      performed through a direct lateral approach using bone anchors for abductor
      mechanism repair was evaluated at 8 to 12 (mean 10.2) years. Complications
      included anchor migration from the bone in 18 (8.4%) patients, a unique pattern
      of symptomatic progressive osteolysis involving the lateral aspect of the greater
      trochanter in 8 (3.7%) patients, and pathological fracture of the greater
      trochanter in 1 (0.5%) patient. Three patients (1.4%) with trochanteric
      osteolysis required surgical intervention including removal of the anchors,
      debridement and reattachment of the abductor mechanism and repair of a
      pathological fracture. Considering these complications, as well as the
      significant cost, bone anchors are not recommended for abductor mechanism repair
      when using the direct lateral approach for total hip arthroplasty.

PMID- 16446195
TI  - Acetabular revision surgery with the LOR cup: three to 8 years' follow-up.
AB  - A retrospective review was conducted to evaluate the mid-term results of the
      Langsovalen Revisionspfanne oblong revision cup. From July 1995 to March 2000, 41
      acetabular revision surgeries were performed for aseptic loosening of the
      acetabular cup. The acetabular defects were classified as type 2A to 3B,
      according to Paprosky's criteria. Morselized bone grafts were used in 19 cases
      (45.2%) to fill cavitary defects. The mean postoperative follow-up was 63.5
      months (range, 40-99 months). Clinical assessment at follow-up showed a
      significantly improved mean Harris Hip Score from 46 points preoperatively to
      82.2 points postoperatively, whereas the x-ray examination did not show any sign
      of loosening of the cups. Data analysis showed that significantly better results
      were correlated with restoring the hip rotation center and reducing leg length
      discrepancy.

PMID- 16446197
TI  - Changes of the biochemical markers of bone turnover and periprosthetic bone
      remodeling after cemented hip arthroplasty.
AB  - Do periprosthetic bone loss and postoperative levels of the biochemical markers
      of bone turnover correlate? The femoral bone mineral density of 53 patients was
      measured by dual-energy x-ray absorptiometry 1 week and 2, 4, 6, and 12 months
      after cemented total hip arthroplasty (THA). Biochemical markers of bone turnover
      were assayed preoperatively and 3, 8, 16, and 24 weeks post-THA. Greatest bone
      loss was detected in the calcar region (region of interest 7), on average, 16%
      after 1 year. A marker of bone resorption, C-terminal telopeptides of type I
      collagen, increased 21% 3 weeks after THA. A significant correlation between
      periprosthetic bone loss in region of interest 7 after 1 year and type I collagen
      at 3 weeks was seen (r = -0.42, P = .003). Data suggest that periprosthetic bone
      loss is induced by an early postoperative high activity of osteoclasts.
      Counteracting this osteoclast activity with a limited and timely postoperative
      antiresorptive treatment may be concluded for clinical application.

PMID- 16446196
TI  - The effect of surface finish and of vertical ribs on the stability of a cemented
      femoral stem: an in vitro stair climbing test.
AB  - The search for improved femoral fixation in cemented total hip arthroplasty is
      ongoing. Two design variables, surface finish and stem contour, were evaluated.
      Sixteen titanium femoral stems of one design were cemented into fiberglass
      femora. One half of the components had a polished surface and the rest had a
      roughened finish. Within each group, 4 stems had vertically oriented ribs on the
      proximal portion and 4 did not. Micromotion was measured in a stair climbing
      simulator with loading to a joint reaction force of 200 kg for 6 million cycles.
      Micromotion increased throughout the course of the experiment. Stems with a
      polished surface had significantly higher micromotion. Although stems with ribs
      had less micromotion compared with those without ribs, this difference was not
      statistically significant.

PMID- 16446198
TI  - A new device for a V-shaped subtrochanteric osteotomy combined with total hip
      arthroplasty.
AB  - Subtrochanteric femoral shortening and a corrective osteotomy are considered to
      be an integral part of total hip arthroplasty for a completely dislocated hip or
      a severe deformity of the proximal femur. A precise subtrochanteric osteotomy is
      mandatory to achieve good results for such cases. We herein describe a new simple
      device for accurately performing precise subtrochanteric V-shaped osteotomy.

PMID- 16446199
TI  - "Floating total knee": ipsilateral periprosthetic fractures of the distal femur
      and proximal tibia after total knee arthroplasty.
AB  - Currently, there are more than 300000 primary total knee arthroplasty (TKA)
      performed annually in the United States. It is estimated that 0.3% to 2.5% of
      these patients will sustain a periprosthetic fracture in association with a TKA
      [Haidukewych GJ, Jacofsky DJ, Hanssen AD. Treatment of periprosthetic fractures
      around a total knee arthroplasty. J Knee Surg 2003;16:111]. The first report of a
      periprosthetic fracture involving a TKA occurred in 1977 [Callaghan JJ.
      Periprosthetic fractures of the acetabulum during and following total hip
      arthroplasty. Instr Course Lect 1998;47:231]. The majority of periprosthetic
      fractures associated with a TKA are distal femoral fractures [Berry D.
      EPIDEMIOLOGY: hip and knee. In: Callaghan J, Duncan C, editors. Periprosthetic
      fractures after major joint replacement. Philadelphia: WB Saunders; 1999. p.
      183]. Periprosthetic tibial fractures are rare and usually involve the medial
      tibial plateau in the presence of a loose component [Rand JA, Coventry MB. Stress
      fractures after total knee arthroplasty. J Bone Joint Surg Am 1980;62:226,
      Hanssen AD, Stuart MJ]. Treatment of periprosthetic tibial fractures. Clin Orthop
      2000; p. 91]. The following case report describes the management of simultaneous
      ipsilateral distal femoral and proximal tibial periprosthetic fractures
      associated with a TKA. The patient was informed that data concerning the case
      would be submitted for publication. To our knowledge, this "floating total knee"
      injury has not been previously reported.

PMID- 16446200
TI  - Cement venogram--a risk of satisfactory cement pressurization.
AB  - Longevity of cemented femoral components is dependent upon many factors. It is
      certainly related to the cementing technique. A dilemma exists between adequate
      cement pressurization and risk of embolic events. A cementation pressure above
      bleeding pressure, to allow optimum cement bone interdigitation but not high
      enough to produce embolic or cardiorespiratory events, is the ideal situation. We
      present a case where cement pressurization resulted in the appearance of a cement
      venogram on the routine postoperative x-ray.

PMID- 16446202
TI  - Prophylaxis for the thromboembolic disease--recommendations from the American
      College of Chest Physicians--are they appropriate for orthopaedic surgery?

PMID- 16446201
TI  - Fractures of cementless thin-walled cups.
AB  - Cementless threaded cups are commonly used in total hip arthroplasty. A method to
      match the elasticity of the cup to that of natural bone is reducing the wall
      thickness of the implant. Despite good results with this philosophy of
      implantation, we recently observed 3 cases of implant fractures after the
      implantation of such thin-walled cups called "Bicon." We performed a thorough
      analysis of 1 of these cases including a histological examination and a technical
      failure analysis (including scanning electron microscopy) to establish the
      chronology and cause of the failure. Multiple fractures of the thin-walled metal
      back cup were determined to be caused by fatigue. We have concluded that due to
      the specific material and design parameters of this cup, under adverse
      circumstances such as the lack of primary or secondary osteointegration, there is
      a risk of failure due to fatigue.

PMID- 16446204
TI  - Why compare mental health care in European capitals?

PMID- 16446205
TI  - Mental health care in Belgrade--challenges and solutions.
AB  - AIM: To describe principles and characteristics of mental health care in
      Belgrade. METHOD: Based on existing data, service provision, number of
      professionals working in services, funding arrangements, pathways intocare,
      user/carer involvement and specific issues are reported. RESULTS: Disastrous
      events in the country and the region caused an increase of mental and behavioral
      disorders for 13.5% in the last few years, thus making them the second largest
      public health problem (after cerebro-vascular diseases). The overall morbidity
      and mortality are on the rise. Intense acute and chronic stress, as well as the
      accumulated traumas caused significant psychological sequelae, especially to
      vulnerable people. DISCUSSION: Whilst various issues of mental health care in
      Belgrade overlap with those in other European capitals, there are also some
      specific problems and features. Due to prolonged adversities, the health system
      has deteriorated and is facing specific challenges. However, the transformation
      of mental health services has been initiated, with a lot of positive movements,
      such as preparation of the National policy for mental health care as well as the
      Law for protection of mentally ill individuals.

PMID- 16446206
TI  - Mental health care in Berlin.
AB  - AIM: To provide information on the mental health care system in Berlin, Germany.
      METHOD: Using available data we report on the spectrum of mental health care
      services provided in Berlin, the number of professionals working in these
      sectors, funding arrangements, pathways into care, and user/carer involvement.
      RESULTS: The health care system in Berlin consists of a network of inpatient,
      outpatient, ancillary, and rehabilitative facilities, all of which are meant to
      work in a synergistic fashion. However, although the individual treatment options
      are generally well-planned, there is still a lack of co-ordination between them.
      Currently, the entire network is threatened by cuts in state funding for
      ancillary and rehabilitative services, by further reductions in the number of
      hospital beds, and by insurance company cuts in prescription drug budgets, such
      as those used for atypical antipsychotics in outpatient care. DISCUSSION: Despite
      many similarities with the situation in other European capitals, the system of
      mental health care in Berlin suffers from a variety of problems related to co
      ordination and costs that are unique to the German capital.

PMID- 16446207
TI  - Mental health care in London.
AB  - AIM: To describe principles and characteristics of mental health care in London.
      METHOD: Based on existing data, service provision, number of professionals
      working in services, funding arrangements, pathways into care, user/carer
      involvement and specific issues are reported. RESULTS: London experiences high
      levels of need and use of mental health services compared to England as a whole.
      Inpatient and compulsory admissions are considerably higher than the national
      average. Despite having more psychiatric beds and mental health staff, London has
      higher bed occupancy rates and staffing shortages. At the same time there is a
      trend away from institutionalised care to care in the community. CONCLUSION:
      Mental health services in the UK are undergoing considerable reform. These
      changes will not remove the greater need for mental health services in the
      capital, but national policy and funding lends support to cross-agency and pan
      London work to tackle some of the problems characteristic of mental health in
      London. Whilst various issues of mental health care in London overlap with those
      in other European capitals, there also are some specific problems and features.

PMID- 16446208
TI  - Mental health care in Madrid.
AB  - AIM: To describe principles and characteristics of mental health care in Madrid.
      METHOD: Based on existing data, service provision, number of professionals
      working in services, funding arrangements, pathways into care, user/carer
      involvement and specific issues are reported. RESULTS: In Madrid, mental health
      services are organized into 11 zones/areas, divided into 36 districts, where
      there is a mental health outpatient service with a multi-disciplinary team. Home
      treatment and psychosocial rehabilitation services have been developed.
      Specialist programmes exist for vulnerable client groups, including Children and
      Adolescents, Addiction/Alcohol and Older People. The Madrid Mental Health Plan
      (2003-2008) is regarded as the key driver in implementing service improvement and
      increased mental health and well-being in Madrid. It has a meant global budget
      increase of more than 10% for mental health services. Results of the first 2
      years are: an increase in mental health staff employed (17%), four new
      hospitalization units, 50% increase in places for children and adolescents Day
      Hospitals, 62 new beds in long care residential units, development of specific
      programmes for the homeless and gender-based violence, a significant investment
      in information systems (450 new computers) and development of best practice and
      operational guidelines. Mental health system was put to the test with Madrid's
      March 11th terrorist attack. A Special Mental Health Plan for Affected people was
      developed. DISCUSSION: Unlike some European countries, public mental health
      service is the main heath care provider. There are no voluntary agencies
      bcollaborating with mental health care. Continuity of care and coordination
      between all mental health resources is essential in service delivery. Increased
      demand of care for minor psychiatric disorders, children and adolescent mental
      health care, and implementation of rehabilitation and residential facilities for
      chronic patients are outstanding challenges similar to those in other European
      capitals. Overall, the mental health system had successfully coped with last
      year's increased care demand after March 11th terrorist attack in Madrid.

PMID- 16446209
TI  - Mental health care in Paris.
AB  - AIM: Characterised by its population density, cultural and ethnic diversity,
      familial fragmentation and high levels of HIV/AIDS, crime and homelessness, Paris
      poses specific problems with regard to mental healthcare. METHODS:
      Epidemiological studies show high rates of generalised anxiety and drug and
      alcohol abuse and dependence, greater use of psychoactive medication and, at the
      same time, apprehension about looking after mentally ill family members at home.
      RESULTS: Although the Greater Paris area has a much higher density of GPs and
      specialists than the national mean, there are considerable variations within the
      region itself, with the central area having up to four times as many GPs or
      psychiatrists as the outer suburbs. On the other hand, although the number of
      mental health medical acts and the number of people receiving mental health care
      have been rising dramatically over the last 15 years, Paris has considerably less
      adult psychiatry beds and day care places per head of population than the rest of
      France. DISCUSSION: Current planning targets include a more equitable
      distribution of mental health care service provision for the rapidly evolving
      urban population, early prevention of psycho-affective disorders, suicide and
      drug and alcohol misuse and the creation of low threshold services for
      adolescents in difficulty.

PMID- 16446210
TI  - Mental health care in Prague.
AB  - AIM: To describe principles and characteristics of mental health care in Prague.
      METHOD: Based on existing data, service provision, number of professionals
      working in services, funding arrangements, pathways into care, user/carer
      involvement and specific issues are reported. RESULTS: Mental health care in
      Prague has a special position in the Czech Republic. Prague has the longest
      tradition of psychiatric treatment including the German Psychiatric Department of
      the Charles University. The density of services is higher, there are more
      extrainstitutional facilities and acute beds are located in general hospitals.
      DISCUSSION: Whilst various issues of mental health care in Prague overlap with
      those in other European capitals, there also are some specific problems and
      features. After substantial political changes in early 90s, the prevailing
      institutional model of psychiatric care has started to be changed according to
      the Concept of Psychiatric Care prepared by the Czech Psychiatric Association and
      approved by the Ministry of Health. However, stigma connected with mental
      disturbances is still present and there are not enough financial resources and
      will to put these plans rapidly into the practice.

PMID- 16446211
TI  - Mental health care in Rome.
AB  - AIM: To describe principles and characteristics of mental health care in Rome.
      METHOD: Based on existing data, service provision, number of professionals
      working in services, funding arrangements, pathways to care, user/carer
      involvement and specific issues are reported. RESULTS: After the Italian
      psychiatric reform of 1978, an extensive network of community-based services has
      been set up in Rome providing prevention, care and rehabilitation in mental
      health. A number of small public acute/emergency inpatient units inside general
      hospitals was created (median length of stay in 2002 = 8 days) to accomplish the
      shift from a hospital-based to a community-based psychiatric system of care. Some
      private structures provide inpatient assistance for less acute conditions (median
      length of stay in 2002 = 28 days), whilst the large Roman psychiatric hospital
      was closed in 1999. DISCUSSION: Whilst various issues of mental health care in
      Rome overlap with those in other European capitals, there also are some specific
      problems and features. During the last two decades, the mental health system in
      Rome has been successfully converted to a community-based one. Present issues
      concern a qualitative approach, with an increasing need to foresee adequate
      evaluation, especially considering mental health patients' satisfaction with
      services and economic outcomes.

PMID- 16446212
TI  - Connecting capitals.

PMID- 16446213
TI  - Acute antibody-mediated rejection of cardiac transplants.
AB  - Under the direction of the International Society for Heart and Lung
      Transplantation, a multidisciplinary review of the cardiac biopsy grading system
      was undertaken in 2004, with task forces examining the areas of histopathology of
      rejection, clinical issues, and research. An important new area addressed by the
      Immunopathology Task Force sub-committee was the clinical and diagnostic criteria
      for antibody-mediated rejection. This article is a companion paper to the revised
      working formulation for the standardization of nomenclature in the diagnosis of
      heart rejection and reviews the published literature documenting the serologic
      and morphologic evidence that antibody-mediated rejection is clinically
      significant and associated with graft loss, accelerated transplant-associated
      coronary artery disease, and death. This article also provides a more in-depth
      analysis of antibody-mediated rejection developed by the Immunopathology Task
      Force for revision of the 1990 working formulation for the standardization of
      nomenclature in the diagnosis of heart rejection.

PMID- 16446214
TI  - Bolivia 6,000 m: achieving new heights after heart transplantation.

PMID- 16446216
TI  - First clinical experience with an automatic control system for rotary blood pumps
      during ergometry and right-heart catheterization.
AB  - BACKGROUND: At present, most clinically implanted rotary blood pumps are operated
      at constant speed and adjusted by the physician. It is generally assumed that an
      adaptation of pump speed to the patient's physiologic requirements would be
      beneficial. The data provided in this paper, based on hemodynamic and spirometric
      data during exercise in which a pre-load-sensitive control was used, lend
      quantitative support to this assumption. METHODS: An automatic speed control was
      developed and implemented with Matlab on a dSpace controller board. The system
      uses pump speed, pump power, and pump flow as its only input signals. It was
      connected to the clinical hardware of the DeBakey VAD System. The control is pre
      load-sensitive and uses an expert system to detect excessive unloading and
      eventual suction. This system was used to quantify the cardiovascular reaction of
      patients to both automatically controlled and constant pump speed. A sub-group of
      5 patients underwent bicycle ergometry with Swan-Ganz catheterization and
      spiroergometry. RESULTS: The automatic, closed-loop speed control showed robust
      and stable performance. It provided an increase in pump flow (+0.94 +/- 0.5
      liters/min, p < 0.05) compared with constant-speed mode in response to physical
      activity. Pulmonary arterial (PAP) and capillary wedge pressure (PCWP) clearly
      decreased (-7.4 +/- 4.1 mm Hg for PAP and -8.3 +/- 4.2 mm Hg for PCWP, p < 0.05),
      and venous oxygen saturation moderately increased (+5.2%). CONCLUSION: An
      automatic speed-control system for rotary blood pumps was developed and
      demonstrated by spiroergometry to be appropriately responsive to physiologic
      demand.

PMID- 16446215
TI  - Peri-operative renal function and outcome after orthotopic heart transplantation.
AB  - BACKGROUND: Renal insufficiency is an established risk factor in patients
      undergoing cardiovascular surgery. We sought to evaluate the relationship between
      renal function and outcomes after orthotopic heart transplantation (OHT).
      METHODS: We conducted a retrospective review of 622 adults who underwent 628
      consecutive OHTs between 1994 and 2001 at our institution. The recipients were
      divided into either normal (Group 1) or impaired (Group 2) pre-operative renal
      function. Impaired renal function was defined as creatinine clearance (CrCl) < 40
      ml/min (Cockroft-Gault formula). Meanwhile, patients in Group 1 (normal) were
      defined by CrCl > or = 40 ml/min. The primary end points of the study were early
      and late mortality. The secondary end point included post-operative renal failure
      defined by the requirement of dialysis or renal allograft in the early post
      operative period. The Kaplan-Meier method was used to determine actuarial
      survival. RESULTS: Early mortality was 7% (38/531) in Group 1 and 17% (16/96) in
      Group 2 (p = 0.002). Similarly, the death rate per 100 patient-years was 4.8 and
      8.1 for the groups, respectively (p = 0.03). Nine percent of patients in Group 1
      required post-operative dialysis (49/531), whereas 32% of recipients in Group 2
      required this intervention (31/96) (p < 0.001). Early mortality was 41% for
      patients requiring post-operative dialysis and 3% for those not requiring such
      intervention (p < 0.001). Early mortality after post-operative dialysis was 41%
      (20/49) in Group 1 and 42% (13/31) in Group 2 (p = 0.2). CONCLUSIONS: CrCl < 40
      ml/min is a useful marker for increased post-operative renal failure and
      mortality. Recipients who require post-operative dialysis have greatly increased
      mortality regardless of pre-operative CrCl. Dialysis in patients after heart
      transplantation carries a prohibitive risk. Dialysis as a bridge to renal
      transplantation may reduce this high mortality rate.

PMID- 16446217
TI  - Brain natriuretic peptide is produced both by cardiomyocytes and cells
      infiltrating the heart in patients with severe heart failure supported by a left
      ventricular assist device.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) is a cardiac neurohormone synthesized
      in cardiac ventricles as a result of increased wall stress. Left ventricular
      assist device (LVAD) support in patients with end-stage heart failure results in
      reduced wall stress and therefore may change BNP levels in the heart. METHODS:
      BNP plasma levels were measured in 17 patients with end-stage HF before LVAD
      implantation and at 1 week, 1 month, and 3 months after LVAD support. BNP
      messenger RNA (mRNA) expression in cardiac biopsy specimens of 27 patients before
      and after LVAD support was determined by quantitative polymerase chain reaction.
      Immunohistochemistry (IHC) and IHC-double staining was used in biopsy specimens
      from 32 patients before and after LVAD support to localize the BNP protein
      expression in the heart. RESULTS: BNP plasma levels significantly decreased from
      1,872 +/- 1,098 pg/ml before implantation to 117 +/- 91 pg/ml at 3 months after
      LVAD implantation. This decrease in plasma levels was accompanied by a
      significant decrease in mRNA expression (relative quantity) in the heart. IHC and
      IHC-double staining showed BNP immunoreactivity in the cardiomyocytes,
      endothelial cells, infiltrating T cells, and macrophages. CONCLUSIONS: The
      significant decrease in serum BNP concentration after LVAD support coincides with
      a decrease in BNP mRNA and protein expression in the heart. BNP is produced in
      the left ventricle not only by cardiomyocytes but also by endothelial cells, T
      cells, and macrophages. Unloading of the left ventricle by a LVAD results in
      decreased BNP expression in the heart and plasma and may play an important role
      in the reverse remodeling process of the heart.

PMID- 16446218
TI  - Clinical performance with the Levitronix Centrimag short-term ventricular assist
      device.
AB  - BACKGROUND: The Levitronix ventricular assist device (VAD) is a centrifugal pump
      designed for extracorporeal support and that operates without mechanical bearings
      or seals. The rotor is magnetically levitated so that rotation is achieved
      without friction or wear, which seems to minimize blood trauma and mechanical
      failure. The aim of this study is to report our early results with the Levitronix
      Centrimag device. METHODS: Between June 2003 and April 2005, 18 patients (pts)
      were supported using the Levitronix at our institution. Fourteen were male. Mean
      age was 40.3 +/- 18.3 (range 8 to 64) years. Indications for support at
      implantation were: post-cardiotomy cardiogenic shock in 12 cases (Group A), and
      bridge to decision regarding long-term ventricular support in 6 cases (Group B).
      RESULTS: Mean support time was 14.2 +/- 15.2 days for all patients (range 1 to 64
      days). Operative (30-day) mortality was 50% (9 pts). Six pts were in Group A and
      3 pts were in Group B. Overall, 6 pts (33%) were discharged home and are
      presently alive and well (mean follow-up 13 months, range 5 to 17 months).
      Bleeding requiring re-operation occurred in 8 cases (44%), cerebral
      thromboembolism in 1 and pulmonary embolism in 1. There were no device failures.
      CONCLUSIONS: The Levitronix functioned well and proved to be useful in patients
      with extremely poor prognosis previously considered non-suitable for a long-term
      assist device. The device was technically easy to implant and manage. There was
      no device dysfunction and complications were acceptable or consistent with other
      devices. Survival to explant or a definitive procedure (VAD or transplantation)
      was encouraging.

PMID- 16446219
TI  - Coronary vasomotor response to the selective B1-kinin-receptor agonist Des-Arg9
      bradykinin in humans.
AB  - OBJECTIVES: The aim of the present study was to assess the effects of selective
      B1-receptor stimulation with des-Arg9-bradykinin on coronary vasomotion in
      transplanted and non-transplanted patients. BACKGROUND: Bradykinin B1-receptors
      have been identified on endothelial and smooth muscle cells in human coronary
      arteries in vitro; however, their physiologic role in the coronary circulation is
      unknown. METHODS: Twelve heart transplant patients were compared with 10 control
      subjects at 3.2 +/- 2.2 months after surgery. Coronary flow velocity was measured
      using guide-wire Doppler. The diameter of 3 epicardial segments of the left
      coronary artery and coronary blood flow were assessed at baseline, immediately
      after infusions of increasing doses of des-arginine(Arg9)-bradykinin at estimated
      coronary blood concentrations of 5.4 x 10(-9), 5.4 x 10(-8), 5.4 x 10(-7) and 1.6
      x 10(-6) mol/liter, and of acetylcholine at 10(-8), 10(-7) and 10(-6) mol/liter).
      RESULTS: Des-Arg9-bradykinin induced a similar decrease in all measured
      epicardial diameters in both groups and no change in coronary blood flow.
      Vasoconstriction was significant only at the 2 highest concentrations: -6 +/- 9%
      (p < 0.01) and -7 +/- 11% (p < 0.01) in control subjects, and -8 +/- 8% (p <
      0.001) and -9 +/- 11% (p < 0.001) in heart transplant patients. Acetylcholine
      induced significant epicardial vasodilation in control subjects and
      vasoconstriction in transplant patients. The presence of allograft rejection did
      not modify the responses to des-Arg9-bradykinin with regard to both conductance
      and resistance vessels. CONCLUSIONS: Kinin B1-receptors exist and can be
      stimulated in humans. The vasoconstrictive action on epicardial coronary arteries
      of des-Arg(9)-bradykinin in humans argues for a predominant action of B1-receptor
      stimulation at the level of smooth muscle cells.

PMID- 16446220
TI  - Leukocyte suppression is associated with improved clinical outcomes in children's
      status after orthotopic heart transplantation.
AB  - BACKGROUND: Leukocyte suppression is a sequela of immunosuppressive therapy after
      orthotopic heart transplantation and may result in discontinuation of anti
      proliferative agents. Clinical outcomes in this patient population have not been
      well delineated. METHODS: This study was a retrospective review of children who
      underwent orthotopic heart transplantation at our institution from 1986 to 2003.
      Leukocyte suppression was defined as a white blood cell count <5,000, prompting
      the withdrawal of anti-proliferative agents. The population was divided into 2
      groups, leukosuppressed (LS) and non-leukosuppressed (NLS), and their clinical
      outcomes were compared. RESULTS: The study included 109 patients, of which 44
      (40%) became leukosuppressed. The 2 groups were similar regarding demographic
      data and initial management. The LS Group had a significantly decreased incidence
      of rejection, being 7 times less likely to have recurrent rejection (p = 0.001).
      The median time to rejection was 0.8 +/- 0.6 years for the NLS Group, whereas the
      median time to rejection was not yet reached at 17 years for the LS Group. The LS
      Group also tended toward a decreased incidence of retransplantation or death (p =
      0.06). The organ "half-life" in the NLS Group was 7.5 years vs 12.5 years in the
      LS Group. There was no difference between the 2 groups in regards to other
      adverse effects of immunosuppression. CONCLUSIONS: Children who have undergone
      orthotopic heart transplantation and subsequently become leukosuppressed have a
      lower incidence of rejection and a tendency toward less organ loss than children
      who do not become leukosuppressed, without having an increased incidence of
      adverse side effects.

PMID- 16446221
TI  - Modulation of natural killer (NK) receptors on NK (CD3-/CD56+), T (CD3+/CD56-)
      and NKT-like (CD3+/CD56+) cells after heart transplantation.
AB  - BACKGROUND: After undergoing heart transplantation and the subsequent compulsive
      immunosuppressive treatments, patients are at risk of rejection episodes,
      infectious complications or cancer development. Thus, it is probable that the
      various subsets of peripheral cytotoxic lymphocytes are modulated in such
      patients. This area of study can now be investigated by examining the numerous
      recently described natural killer (NK)-cell-related surface receptors. METHODS: A
      prospective cohort of 60 heart transplant recipients and 60 controls was studied.
      The partitioning of lymphocyte subsets, especially NK (CD3-/CD56+), T (CD3+/CD56
      ) and NKT-like (CD3+/CD56+) cells, was compared in both groups using multi
      parametric flow cytometry. Moreover, expression of a series of seven NK-related
      receptors was compared on the three subsets defined by CD56 expression. RESULTS:
      A significant increase in NK-cell levels was observed in transplanted patients,
      as compared with controls, whereas T and NKT-like cells were in similar
      proportions in both groups. Two NK-related receptors showed significantly
      different levels of expression in heart transplant recipients: the cytotoxic
      effector, CD244, which was in a significantly increased proportion on T and NKT
      like cells; and the activating receptor, CD161, which was expressed significantly
      less on NK and NKT-like cells, but more on T cells. CONCLUSIONS: These findings
      indicate that cytotoxic NK-related cells, increased in proportion, also display
      increased levels of activity-associated markers in heart transplant recipients.
      Viral infection or the immunosuppressive regimen could be responsible for the
      modulation of regulatory receptors on NK and NKT-like cells in heart transplant
      recipients.

PMID- 16446222
TI  - Vascular endothelial growth factor C-induced collateral formation in a model of
      myocardial ischemia.
AB  - BACKGROUND: Besides being a known lymphangiogenic activator, vascular endothelial
      growth factor (VEGF)-C may express angiogenic potential by proteolytic cleavage
      and activation of endothelial cells. We assessed myocardial collateral formation
      and functional changes after adenovirus-mediated VEGF-C gene transfer in an
      ischemic porcine model. METHODS: Fifteen Landrace piglets underwent Ameroid
      induced gradual occlusion of the left circumflex artery (LCx) and consequent
      progressive myocardial ischemia. Three weeks after Ameroid placement, the animals
      underwent gated 99mTc SPECT during rest and stress, in vivo angiography and 18FDG
      PET. Pigs were randomized to intramyocardial injections of adenoviruses encoding
      vascular endothelial growth factor (VEGF-C; n = 7) or control beta-galactosidase
      (LacZ; n = 5). Four weeks later, the examinations were repeated and histology was
      analyzed. RESULTS: Angiography showed significant progression of LCx stenosis in
      both groups during the treatment period. Left ventricular wall thickening (LVWT)
      at the LCx area in gated 99mTc SPECT remained unchanged in the VEGF-C group,
      indicating that VEGF-C prevented progression of myocardial ischemia, whereas LVWT
      deteriorated in the LacZ group (p = 0.042). Semi-quantitative assessment of 18FDG
      PET suggests more reduction in ischemia in the adVEGF-C group than in controls (p
      = 0.052). Angiography showed significant clustering of collaterals in the adVEGF
      C gene transfer area compared that in LacZ (p = 0.004). von Willebrand factor
      staining revealed a significantly (p = 0.03) greater number of microvessels in
      the adVEGF-C-treated myocardium. CONCLUSIONS: This appears to be the first large
      animal study in which, during progressive ischemia, functional and metabolic
      benefits of intramyocardial VEGF-C gene transfer were apparent. VEGF-C-induced
      collateral formation occurred at the site of gene transfer. The angiogenic
      potency of VEGF-C deserves further study as a therapeutic option.

PMID- 16446223
TI  - Tissue Doppler imaging in patients with advanced heart failure: relation to
      functional class and prognosis.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) provides rapid assessment of systolic
      and diastolic myocardial function. However, the added value of TDI to standard
      Doppler echocardiographic measurements in predicting symptoms and outcome of
      advanced heart failure remains unknown. METHODS: The study cohort comprised 45
      patients with congestive heart failure, defined as New York Heart Association
      functional class III and IV, who were referred to our department for evaluation
      for heart transplantation. Twenty healthy subjects were the controls.
      Conventional echo Doppler was used to assess left ventricular (LV) ejection
      fraction, peak velocities of transmitral early and late diastolic LV filling, the
      ratio of transmitral early to late LV filling velocity, and E-deceleration time.
      TDI measurements recorded at the mitral annulus included systolic velocity, early
      and late diastolic velocities, and the ratio of early to late diastolic velocity.
      The ratio of transmitral early LV filling velocity to early diastolic TDI
      velocity of the mitral annulus (E/E') was calculated. All patients were followed
      for cardiac-related death and hospitalization for heart failure. RESULTS:
      Patients with functional class IV had a significantly higher E/E' ratio than did
      patients with functional class III (12.9 +/- 2.8 vs 8.3 +/- 1.7, p < 0.001) and
      the controls (5.4 +/- 1.3, p < 0.001). Except for transmitral late filling
      velocity, all conventional echo Doppler parameters and TDI variables
      significantly correlated with functional class. On multivariate stepwise
      analysis, however, the E/E' ratio was the only independent predictor of
      functional class (p = 0.003). E/E' also correlated with cardiac mortality and
      hospitalization. CONCLUSION: Conventional Doppler indices and TDI parameters
      correlated with functional class in patients with advanced heart failure. The
      E/E' ratio, which probably reflects high LV end-diastolic pressure, was the best
      measure for differentiating patients with functional class III and IV, and it
      also correlated with cardiac mortality and hospitalization for worsening heart
      failure, thereby providing additional value to standard echocardiographic
      measures.

PMID- 16446225
TI  - Health-related quality-of-life determinants in lung transplantation.
AB  - BACKGROUND: In light of recent reviews, we examined the effect of individual and
      clinical factors, associated with lung transplantation (LTx), on health-related
      quality of life (HRQL). METHODS: HRQL was measured cross-sectionally on 34
      candidates and 71 lung transplant recipients, using the Short Form 36-item
      questionnaire (SF-36), of the Medical Outcomes Study. Multivariate analysis was
      used to model each of the 8 SF-36 health domains as a function of individual
      determinants associated with LTx. The original model included: transplant status;
      age; gender; time since LTx; forced expiratory volume in 1 second (% predicted);
      type of LTx received; lung disease; whether within 1 month of the interview the
      participant was hospitalized; days in hospital (LOS); and whether infection or
      rejection occurred. Final models were chosen using a statistical cutoff of alpha
      < or = 0.10 to remain in the model. RESULTS: After adjusting for important
      predictors, lung transplantation was positively associated with all domains (p <
      0.005). Although time since transplantation negatively influenced the physical-
      and social-related domains (p < 0.05), the effect was small. Clinically
      meaningful effects on physical HRQL domains were observed with disease (p <
      0.01), type of transplant received (p < 0.05) and hospital stay (p < 0.05).
      Gender played a role in mental health (p < 0.05). CONCLUSIONS: Clinical events
      leading to hospitalization limit some HRQL domains. Different factors influence
      the physical, social and mental health domains, and thus future studies should
      focus on domain-specific variables to optimize HRQL. The HRQL benefit conferred
      from LTx renders it a worthwhile option for end-stage lung disease patients with
      important physical limitations.

PMID- 16446226
TI  - Statin-associated QTc interval shortening as prognostic indicator in heart
      transplant recipients.
AB  - Statin treatment promotes survival after cardiac transplantation by reducing
      cholesterol levels, allograft rejection, and transplant coronary artery disease.
      Analysis of data from 114 heart transplant recipients (including 86 treated with
      statins for < or =1 year post-transplantation) revealed that statins were
      associated with shortened corrected QT intervals (QTc), reduced low-density
      lipoprotein cholesterol, and reduced transplant coronary artery disease incidence
      at 1 year and improved survival at 5 years. Statin-associated QTc shortening thus
      appears to be a favorable prognostic sign after transplantation.

PMID- 16446227
TI  - Disseminated acanthamoebiasis after lung transplantation.
AB  - Protozoan infections in organ transplant recipients are rare. We report a fatal
      case of disseminated acanthamoebiasis in a bilateral lung transplant recipient
      that presented with cutaneous lesions, respiratory failure, and seizures.
      Acanthamoeba infection may be identified in transplant recipients with exposure
      to water who develop non-healing cutaneous ulcers with granulomatous
      inflammation. Cutaneous lesions are the initial manifestation of infection and a
      harbinger of dissemination. Early institution of combination anti-microbial
      therapy is therefore necessary for effective treatment and prevention of lethal
      spread to the central nervous system.

PMID- 16446224
TI  - A comparative study of cardiac preservation with Celsior or University of
      Wisconsin solution with or without prior administration of cardioplegia.
AB  - BACKGROUND: We have previously reported the cardiac functional and metabolic
      benefits of administration of extracellular-type cardioplegia before preservation
      with University of Wisconsin solution. Celsior solution was designed to be used
      both as an arresting solution and a storage solution for heart transplantation.
      The objective of the present study is to compare cardiac function of hearts
      arrested and preserved with Celsior solution to hearts arrested with cardioplegia
      followed by preservation with UW solution. METHODS: Rabbit hearts were divided
      into 4 groups: in the Celsior group, hearts were arrested and preserved with
      Celsior solution; in the C-Celsior group, hearts were arrested by an
      extracellular-type cardioplegia and preserved with Celsior solution; in the UW
      group, hearts were arrested and stored in University of Wisconsin solution; and,
      in the C-UW group, hearts were arrested with extracellular-type cardioplegia and
      stored in University of Wisconsin solution. After 6 hours of preservation,
      cardiac function was measured using modified Frank-Starling curves in the
      isolated blood-perfused working heart. RESULTS: Cardiac function in the Celsior
      group was inferior to that in both the C-UW group and UW group. The C-Celsior
      group demonstrated inferior cardiac function compared with the Celsior group (p <
      0.01), whereas no significant difference was observed between the C-UW and UW
      groups. CONCLUSIONS: Celsior solution did not surpass UW solution regardless of
      the use of cardioplegia. Further studies are required to develop optimal solution
      for use as both an arresting solution and a storage solution.

PMID- 16446228
TI  - Reversible sirolimus-associated pneumonitis after heart transplantation.
AB  - Sirolimus (rapamycin) and everolimus are immunosuppressive agents that inhibit
      cardiac allograft vasculopathy. Sirolimus has been widely used in renal
      transplantation, and its use in heart transplantation is increasing. Sirolimus
      associated pneumonitis has been described in renal transplant patients. Two cases
      of sirolimus-associated pneumonitis have been reported after cardiac
      transplantation. Only 1 case has been described in detail, and this had a fatal
      outcome. Here, we present a case of sirolimus-associated interstitial pneumonitis
      in a cardiac transplant recipient that resolved completely with withdrawal of the
      drug and treatment with corticosteroids.

PMID- 16446229
TI  - Orthotopic retransplantation in heterotopic transplant recipients: 3 case
      reports.
AB  - We report 3 patients who initially underwent heterotopic transplantation due to a
      size mismatch but then later underwent orthotopic retransplantation because of
      heart failure. In each case, the heterotopic graft was left in place, the native
      heart was removed, and the new allograft was placed orthotopically. This
      technique resulted in reduced postoperative morbidity and excellent long-term
      outcomes.

PMID- 16446230
TI  - Recovery from hemorrhagic pulmonary damage by combined use of a left ventricular
      assist system and right ventricular assist system and extracorporeal membrane
      oxygenation.
AB  - A 13-year-old boy developed cardiogenic shock secondary to end-stage dilated
      cardiomyopathy and extracorporeal life support (ECLS) was initiated. However,
      pulmonary hemorrhage occurred due to severe pulmonary hypertension. He underwent
      implantation of a left ventricular assist system (LVAS) and right ventricular
      assist system (RVAS) plus extracorporeal membrane oxygenation (ECMO) shunting
      between the right and left atrium. Pulmonary damage was resolved and RVAS-ECMO
      was terminated after 8 days of support.

PMID- 16446231
TI  - Permanent use of a ventricle assist device for dilated cardiomyopathy in
      Friedreich's ataxia.
AB  - A patient with Friedreich's ataxia was hospitalized due to dilated cardiomyopathy
      and heart failure. We received informed consent from the patient and his family
      for implantation of an implantable ventricular assist device (VAD) as permanent
      support. At the one-year follow-up examination, the neuromuscular symptoms had
      progressed no further, and he had no VAD systemic failure and complications. This
      is the first case report of VAD implantation in a Friedreich's ataxia patient.

PMID- 16446232
TI  - Intraperitoneal HeartMate left ventricular assist device placement after
      endovascular repair of an abdominal aortic aneurysm.
AB  - The presence of an abdominal aortic aneurysm (AAA) can be a contraindication to
      placement of a HeartMate left ventricular assist device (LVAD) for end-stage
      heart failure. We describe a 65-year-old patient who underwent endovascular
      repair of an AAA before placement of a LVAD as destination therapy for end-stage
      heart failure. This case is the first report of endovascular AAA repair before
      VAD placement. It not only demonstrates the utility of endovascular AAA repair in
      patients with undue co-morbidities, but also that the presence of an AAA should
      not be a contraindication to LVAD placement, if corrected.

PMID- 16446233
TI  - Pressure-volume analysis during axial flow ventricular assist device support.

PMID- 16446234
TI  - Radiation therapy-related cardiovascular disease.

PMID- 16446235
TI  - Concomitant post-transplantation lymphoproliferative disease and therapy-related
      myelodysplastic syndrome after lung transplantation.

PMID- 16446237
TI  - Diversity in care.

PMID- 16446238
TI  - JCAHO'S National Patient Safety Goals 2006.
AB  - The Joint Commission of Accreditation of Healthcare Organizations released their
      first set of National Patient Safety Goals in 2002, which became effective in
      January 2003. This original set of goals is reviewed and a new set published
      every year. This article provides a review of the 2006 National Patient Safety
      Goals with an emphasis on perioperative/perianesthesia implications.

PMID- 16446239
TI  - Brown recluse spider bites: a case report.
AB  - The brown recluse spider is found more commonly in the Southeast and the Central
      Midwest. Its bite is not common because it is a shy spider that only bites if
      cornered. A severe bite may necrose a large area that requires skin grafting;
      systemic reactions rarely occur. This article discusses the brown recluse spider
      and presents a case study of a patient with two spider bites that did require
      extensive grafting.

PMID- 16446240
TI  - Peripheral nerve blocks: understanding the nurse's role.
AB  - This article describes the nursing care and management of patients during and
      after administration of peripheral nerve blocks. We review recommendations for
      patient monitoring, as well as the risks and complications associated with
      anesthetic agents. Several upper and lower extremity blocks, including the Bier
      block, are described. The nursing role in the use of the peripheral nerve
      stimulator is also explained. Throughout the discussion, nursing responsibilities
      are emphasized.

PMID- 16446242
TI  - Volunteering for disaster nursing: one nurse's story. Interview by Maureen
      Iacono.

PMID- 16446241
TI  - Temperature measurement in the phase I PACU.
AB  - Perioperative hypothermia remains a common occurrence in the Phase I PACU.
      Identification of and appropriate intervention for this complication is of prime
      importance in the prevention of adverse outcomes. This article provides an
      overview of perioperative hypothermia and offers a summary of the most common
      methods used to measure body temperature.

PMID- 16446243
TI  - Meeting national standards: taking a deep breath?

PMID- 16446244
TI  - One small step today, one giant leap into yesterday.

PMID- 16446245
TI  - Lidocaine iontophoresis for dermal procedure analgesia.

PMID- 16446246
TI  - Stroke is no joke.

PMID- 16446250
TI  - Trends in tobacco use.
AB  - The use of tobacco can be traced back to ancient times. Its popularity grew
      exponentially during the twentieth century, surging during wartime and with the
      advent of mass media. The tobacco industry in the United States has been under
      constant legal pressure during the past 40 years. Despite the well-known and
      continually increasing morbidity and mortality related to smoking, it continues
      to be a prominent feature in worldwide culture and health.

PMID- 16446247
TI  - Exploring qualitative research for perianesthesia nurses.

PMID- 16446251
TI  - Financial burden of tobacco use: an employer's perspective.
AB  - To assist in determining whether employer-sponsored smoking cessation programs
      can be justified on cost-effectiveness grounds, a review was performed to examine
      the costs imposed on employers by smoking and the extent to which employers can
      recover those costs through successful smoking cessation programs. The magnitude
      of the costs (or cost savings) imposed by employee tobacco use depends on
      workplace factors, including medical coverage (before and after retirement),
      disability and life insurance benefits, level of exposure to workplace pollutants
      associated with smoking-related diseases, employee turnover rate, current smoke
      free area policy, smoking breaks policy, cost of providing smoking areas, and
      type of retirement pension plan.

PMID- 16446252
TI  - The impact of tobacco use and secondhand smoke on hospitality workers.
AB  - Tobacco use has a substantial impact on hospitality industry employees because of
      the disproportionate prevalence of smoking among these workers and because of the
      high levels of secondhand smoke to which they are exposed. The severity of this
      impact is evidenced by the high mortality rates observed among hospitality
      industry workers from diseases related to tobacco smoke exposure. Several states
      and localities have begun to enact laws to protect these workers from secondhand
      smoke exposure. Such policies seem to be effective in reducing exposure and
      improving health among these workers without causing any adverse impact on
      business. Occupational clinicians can play a significant role in protecting the
      health of hospitality workers by supporting laws to create smoke-free workplaces,
      including bars and restaurants, and promoting smoking cessation in these
      worksites.

PMID- 16446253
TI  - Tobacco and law enforcement officers.
AB  - The literature on the prevalence of health hazards faced by law enforcement
      officers indicates that they are at high risk for several morbid diseases and
      conditions, particularly cardiovascular disease and cancer. To mitigate these
      risks, quitting smoking is of the utmost importance. This article focuses on
      reducing tobacco consumption by law enforcement officers in New York.

PMID- 16446254
TI  - Tobacco and the health care industry.
AB  - The 1964 US Surgeon General's report was the first from the medical profession to
      document tobacco as a cause of cancers and other serious illnesses. Over the next
      40 years, numerous health care groups have worked to decrease tobacco use and
      lower the associated morbidity and mortality. Registered nurses are the largest
      group of health care providers and have one of the highest rates of smoking among
      health care professionals. As such, registered nurses are an important population
      to target and treat for nicotine addiction. Hospital-based tobacco control
      programs can provide nurses and other health care professionals with convenient
      on-site treatment. The chronic care model provides a useful framework for
      enhancing tobacco control activities and improving outcomes.

PMID- 16446255
TI  - Tobacco and the movie industry.
AB  - Despite the tobacco industry's voluntary restrictions and its agreement with the
      state attorneys general prohibiting direct and indirect cigarette marketing to
      youth and paid product placement, tobacco use remains prevalent in movies.
      Extensive research provides strong and consistent evidence that smoking in the
      movies promotes smoking. This article summarizes the evidence on the nature and
      effect of smoking in the movies on adolescents (and others) and proposes several
      solutions to reduce adolescent exposure to movie smoking and subsequent smoking.

PMID- 16446256
TI  - Current tobacco control policy trends in the United States.
AB  - This article takes a snap-shot view of current tobacco control laws and where the
      nation is headed. Smoke-free workplace laws are highlighted, and the New York
      campaign experience is explained briefly. The article also creates a view into
      current trends in tobacco excise taxes; youth access laws, US Food and Drug
      Administration regulations of tobacco, tobacco control program funding, and other
      regulatory efforts in municipalities, individual states, and the nation as a
      whole.

PMID- 16446257
TI  - Current trends in international tobacco control.
AB  - The tobacco control policy tools developed in a few rich countries in the 1970s,
      1980s, and 1990s are currently being implemented widely in many poorer countries,
      thanks in part to the astonishing success of the Framework Convention on Tobacco
      Control (FCTC). With smoking rates already high in most of the Third World,
      however, the projections for the twenty-first century are grim: up to 1 billion
      tobacco-caused deaths, which raises the issue of what more can be done,
      particularly to help people who already are addicted to nicotine. Only massive
      and effective smoking cessation programs could reduce this death toll
      significantly, at least in the short-term. Tobacco control's existing tools, if
      widely applied, likely will reduce premature deaths significantly but can be
      expected to leave unacceptably high levels of tobacco-related mortality. This
      finding has sparked fierce discussions among anti-tobacco activists about the
      role of harm reduction in curbing death and disease. This article discusses
      whether harm reduction is possible with the tobacco industry subject to a largely
      unregulated environment for tobacco products.

PMID- 16446258
TI  - Tobacco and carcinogens in the workplace.
AB  - Workplace exposures to carcinogens long have been associated with cancers, and
      corrective measures to limit exposures have resulted in reductions in such
      cancers and improved worker health. Some exposures are currently of historical
      interest, and many current or past exposures are associated with conflicting
      evidence as to causality. We present a brief overview of the effects of exposure
      to asbestos, tobacco, and other known carcinogens.

PMID- 16446260
TI  - Pulmonary and cardiovascular consequences of smoking.
AB  - The extensive worldwide disease burden attributable to tobacco smoking is
      reviewed, with particular attention to the epidemiologic and clinical aspects,
      molecular and cellular mechanisms, and pathophysiology of a variety of smoking
      related pulmonary diseases, and the epidemiology and clinical presentation of
      smoking-related atherosclerotic disease as it affects the cardiovascular system
      cerebral circulation, the aorta, and the peripheral arterial tree.

PMID- 16446259
TI  - Respiratory health consequences of environmental tobacco smoke.
AB  - Over the last several decades there has been a growing interest in examining the
      health consequences of environmental tobacco smoke (ETS). As a result of a wide
      body of research, ETS is now considered an unacceptable and entirely preventable
      public health hazard, and public policy increasingly discourages the presence of
      tobacco smoke in the public domain. This article provides an overview of the
      composition of ETS and the major diseases and disorders strongly linked to ETS,
      emphasizing the effects of ETS on pulmonary function, asthma, and lung cancer.

PMID- 16446261
TI  - Smoking and systemic disease.
AB  - Cigarette smoking is associated with a number of adverse health effects,
      including well-established links to cardiopulmonary disease and several cancers.
      Some of the other important systemic diseases associated with smoking are the
      subjects of this article, such as diabetes mellitus and insulin resistance, and
      thyroid diseases. Also reviewed here is the impact of smoking on male and female
      infertility, on selected dermatologic conditions, and on gastrointestinal
      diseases including peptic ulcer and inflammatory bowel diseases.

PMID- 16446262
TI  - Tobacco and HIV.
AB  - The risks to an HIV-infected person who smokes are dramatically amplified
      compared with the general population. Smoking has been shown to be an independent
      risk factor for non-AIDS-related mortality in patients who have HIV, even in
      patients who receive highly active antiretroviral therapy. It has been
      independently associated with lower scores for quality-of-life indices, such as
      general health perception, physical functioning, bodily pain, energy, and
      cognitive functioning. Over time, considering the significant pathology elicited
      by tobacco, it is hoped that smoking cessation will help reduce the risks of lung
      disease, heart disease, and neoplastic conditions in patients who have HIV and
      increase their general sense of well-being.

PMID- 16446265
TI  - Understanding the multidimensional nature of health promotion for older adults
      through the application of a conceptual framework.
AB  - Over the next three decades, the proportion of Americans over age 65 will grow to
      exceed 25 percent of the population. Although research has shown that health
      promotion and disease prevention interventions for older adults can lead to
      positive health outcomes, our understanding of the effects of health promotion on
      the health and well-being of older people could be improved through the
      development and use of a conceptual framework. This article presents a conceptual
      model for understanding the determinants and consequences of engaging in health
      promotion activities for older adults, describes how to use the model to estimate
      the impact of health promotion programs on a variety of individual- and community
      level outcomes, and then applies the model to two different health promotion
      programs for older persons: REACH II and the Senior Wellness Program.

PMID- 16446263
TI  - Routine PHQ-9 depression screening in home health care: depression, prevalence,
      clinical and treatment characteristics and screening implementation.
AB  - This study aimed to examine: the prevalence and correlates of depression among
      adults age 65 and over on admission to diverse home health care programs; nurse
      compliance with routine screening using the PHQ-9; and concordance between the
      number of depressed individuals identified by the PHQ-9 and Medicare-mandated
      nursing assessment following targeted nurse training in identifying depression
      among the elderly using a standard diagnostic screen. Data are drawn from routine
      screening of 9,178 patients (a 77% screening compliance rate). Of all patients
      screened, 782 (8.5%) met criteria for probable major depression and 148 (1.6%)
      for mild depression. Concordance between nurse identified depression via PHQ-9
      and OASIS depression assessment improved over that reported in previous studies.
      Findings suggest that the use of a routine screening tool for depression can be
      implemented with minimal in-house training and improves detection of depression
      among older adults with significant physical and functional impairment.

PMID- 16446264
TI  - Evaluating best practices for social model programs for adults with Alzheimer's
      disease in South Carolina.
AB  - Our study has two objectives. First, we reviewed the literature, and identified
      best practices for social model day programs providing care for adults with
      Alzheimer's disease (AD). Second, in-depth telephone interviews were conducted
      with directors in all social model day programs (n = 21) dedicated to serving
      adults with AD in South Carolina to compare practices to those identified.
      Programs implemented many best practices, despite their rural location and small
      size. All programs assessed clients' activity preferences, and reassessed
      activity effectiveness regularly. Most programs provided volunteers and staff
      with AD-focused training. Many programs incorporated innovative programming such
      as intergenerational activities. Most programs were offered in a setting not
      designed for adult day services; thus many programs did not provide suggested
      environmental features such as extra lighting or walking paths. Most programs
      evaluated activities from caregivers' perspectives. All programs provided support
      for caregivers. Practice and policy recommendations are described.

PMID- 16446266
TI  - Impact of the Medicare interim payment system on length of use in home care among
      patients with Medicare-only payment source.
AB  - Using data from the 1996 and 2000 National Home and Hospice Care Surveys (N =
      2,455), we examined length of use in home care among patients with Medicare-only
      payment source before and during the Medicare interim payment system (IPS).
      Logistic regression analyses revealed that patients were 2.9 times more likely to
      be discharged within 60 days during IPS than before IPS. The impact of Medicare
      IPS on length of use in home care among patients with Medicare only was stronger
      than what the existing literature indicates, which combines Medicare patients
      with multiple payment sources and patients with Medicare-only together.

PMID- 16446267
TI  - Assuring quality care: exploring strategies of Medicaid E&D Waiver providers.
AB  - Implementing quality assurance (QA) programs in unregulated non-institutional
      settings remains a challenge for home- and community-based service providers. A
      sample of 65 Elderly and Disabled (E&D) Waiver providers were presented with
      eight problem scenarios commonly found in homecare services. Each of the
      respondents was able to identify strategies they would use to recognize and
      address each problem. Findings suggest providers currently use multiple
      mechanisms as part of their overall QA program. Discussion focuses on the
      strengths of using multiple approaches and on increasing provider awareness of
      complementary QA strategies and reducing the reliance on staff report as a major
      QA strategy.

PMID- 16446268
TI  - Interdisciplinary educational approaches to promote team-based geriatrics and
      palliative care.
AB  - Despite the increasing public demand for enhanced care of older patients and
      those with life-threatening illness, health professionals have had limited formal
      education in geriatrics and palliative care. Furthermore, formal education in
      interdisciplinary team training is limited. In order to remedy this situation,
      proactive interventions are being undertaken so that education and training in
      palliative care is being embedded within the training of physicians, nurses,
      social workers, as well as other associated health team members. This article
      discusses various educational approaches to interdisciplinary team-based
      geriatric and palliative care, highlighting the interdisciplinary didactic and
      clinical educational opportunities offered by an Interprofessional Palliative
      Care Fellowship Program, as well as an Associated Health Training Program at the
      Geriatrics Research, Education, and Clinical Center, Bronx Veteran's Medical
      Center. The article further describes the educational initiatives in palliative
      care offered through the Veteran's Integrated Service Network (VISN). Innovative
      educational strategies are discussed within the context of the existing
      literature on interdisciplinary health care team training.

PMID- 16446269
TI  - Effects of a geriatrics interdisciplinary experience on learners' knowledge and
      attitudes.
AB  - This study examines the impact of an interdisciplinary training program on
      knowledge and attitudes of learners from four health care programs: medicine,
      pharmacy, social work, and nursing. Sixty-two learners participated in a 4-day
      educational program (one day each week for 4 weeks) focusing on interdisciplinary
      geriatric care. After completing the program, learner scores improved on a
      knowledge test and two attitudinal subscales, and they reported a positive
      training experience. A short-term interdisciplinary educational intervention can
      have an impact on learners' knowledge of and attitudes toward older adults, and
      improve their understanding and confidence in participating in an
      interdisciplinary collaborative care team.

PMID- 16446270
TI  - Teaching interdisciplinary geriatrics ambulatory care: a case study.
AB  - Interdisciplinary health care training is advocated by numerous government and
      philanthropic organizations. Educators in the health professions are increasingly
      offering training in interdisciplinary health care in a variety of contexts,
      including ambulatory settings. This paper describes a three-year program to teach
      skills in interdisciplinary care to learners from internal medicine, social work,
      pharmacy, and nursing in a geriatrics clinic at a major academic institution in
      the United States. Framed in a critical review of existing evidence for the
      effectiveness of interdisciplinary training and health care and expert
      recommendations, specific recommendations are made to educators interested in
      interdisciplinary training in ambulatory settings.

PMID- 16446271
TI  - Medical student and senior participants' perceptions of a mentoring program
      designed to enhance geriatric medical education.
AB  - In 2000, the Senior Mentor Program was implemented as an innovative,
      instructional method in the University of South Carolina's medical school
      curriculum designed to enhance and strengthen student training in geriatrics.
      This study qualitatively analyzed second- year medical students' and senior
      participants' perceptions of and attitudes towards the Senior Mentor Program as
      an effective learning modality. A total of 36 second-year students from two
      consecutive classes (2002-2003) and 42 senior mentors at USC's School of Medicine
      participated in five and seven separate focus group interviews, respectively. The
      group discussions were transcribed and a content analysis performed using NVivo.
      The coding scheme and analyses were driven by the data collected and recurrent
      themes were examined across all focus groups. Overall, student and senior mentor
      participants viewed the program positively. Thematic comparisons by participant
      type indicate a shared view that the mentoring relationship has a far-reaching,
      educational, professional, and personal impact. Both students and seniors agreed
      that myths and stereotypes about aging were dispelled and students indicated that
      a close, caring relationship with an older person will change they way they
      practice. A longitudinal mentoring program that pairs students with community
      dwelling seniors can be a valuable addition to traditional geriatric curricular
      activities designed to increase students' skills and compassion for caring for
      older adults.

PMID- 16446272
TI  - The educational impact of a computer-based training tutorial on dementia in long
      term care for licensed practice nursing students.
AB  - The purpose of this study was to examine whether training with a multimedia
      tutorial would have an impact on LPN students' knowledge of dementia care,
      attitudes toward dementia care, and self-efficacy ratings. A total of 38 nursing
      students participated. Pre-post comparisons of outcome measures revealed
      significant improvements in knowledge, attitudes, and self-efficacy ratings.
      Results of post-training satisfaction and usability questionnaires indicate that
      participants found the tutorials easy to understand and easy to use. These data
      support the effectiveness of the dementia tutorial and the use of computer-based
      training in educating our long-term care workforce.

PMID- 16446273
TI  - Prescribing exercise for older adults: A needs assessment comparing primary care
      physicians, nurse practitioners, and physician assistants.
AB  - To inform the development of educational programming designed to teach providers
      appropriate methods of exercise prescription for older adults, the authors
      conducted a survey of 177 physicians, physician assistants, and nurse
      practitioners (39% response rate). The survey was designed to better understand
      the prevalence of exercise prescriptions, attitudes, barriers, and educational
      needs of primary care practitioners toward older adults. Forty-seven percent of
      primary care providers report not prescribing exercise for older adults; 85% of
      the sample report having no formal training in exercise prescription.
      Practitioner attitudes were positive toward exercise, but were not predictive of
      their exercise prescribing behavior, which indicates that education efforts aimed
      at changing attitudes as a way of increasing exercise-prescribing behaviors would
      not be sufficient. In order to facilitate and reinforce practice changes to
      increase exercise-prescribing behaviors of primary care providers, results
      suggest the need for specific skill training on how to write an exercise
      prescription and motivate older adults to follow these prescriptions.

PMID- 16446275
TI  - Digital Mammography: An Update.
AB  - Mammography remains important for early detection and diagnosis of malignant
      breast diseases. In recent years, digital imaging technology has been able to
      address the challenges inherent in film-screen mammography and improve many
      aspects of care. Promising techniques include needle biopsies guided by digital
      mammography, computer-assisted diagnosis, tomosynthesis, contrast-enhanced
      mammography and scintimammography. Although it is unlikely that digital
      mammography will revolutionize how breast cancer is treated, it continues to
      enhance and help provide timely and accurate detection and diagnosis.

PMID- 16446276
TI  - Thermodynamics of RNA-RNA binding.
AB  - BACKGROUND: Reliable prediction of RNA-RNA binding energies is crucial, e.g. for
      the understanding on RNAi, microRNA-mRNA binding and antisense interactions. The
      thermodynamics of such RNA-RNA interactions can be understood as the sum of two
      energy contributions: (1) the energy necessary to 'open' the binding site and (2)
      the energy gained from hybridization. METHODS: We present an extension of the
      standard partition function approach to RNA secondary structures that computes
      the probabilities Pu[i, j] that a sequence interval [i, j] is unpaired. RESULTS:
      Comparison with experimental data shows that Pu[i, j] can be applied as a
      significant determinant of local target site accessibility for RNA interference
      (RNAi). Furthermore, these quantities can be used to rigorously determine binding
      free energies of short oligomers to large mRNA targets. The resource consumption
      is comparable with a single partition function computation for the large target
      molecule. We can show that RNAi efficiency correlates well with the binding
      energies of siRNAs to their respective mRNA target. AVAILABILITY: RNAup will be
      distributed as part of the Vienna RNA Package, www.tbi.univie.ac.at/~ivo/RNA/

PMID- 16446277
TI  - AMiGA: the arthropodan mitochondrial genomes accessible database.
AB  - The Arthropodan Mitochondrial Genomes Accessible database (AMiGA) is a relational
      database developed to help in managing access to the increasing amount of data
      arising from developments in arthropodan mitochondrial genomics (136
      mitochondrial genomes as of September 2005). The strengths of AMiGA include (1) a
      more accessible and up-to-date database containing a more comprehensive set of
      mitochondrial genomes for this phylum, (2) the provision of flexible search
      options for retrieving detailed information such as bibliographical data, genomic
      graphics, FASTA sequences and taxonomical status, (3) the possibility of enhanced
      comparative analyses by multiple alignment of single or concatenated sets of
      genes, (4) more accurate and updated information resulting from a specific
      curation process called AMiGA Notes and (5) the possibility of including
      unpublished sequences in a password-restricted area for comparative analysis with
      the other sequences stored in the database. AVAILABILITY:
      http://amiga.cbmeg.unicamp.br CONTACT: lessinger@amiga.cbmeg.unicamp.br
      SUPPLEMENTARY INFORMATION: Detailed information, including an illustrated
      tutorial, is available from the above URL.

PMID- 16446278
TI  - Discovering motif pairs at interaction sites from protein sequences on a proteome
      wide scale.
AB  - MOTIVATION: Protein-protein interaction, mediated by protein interaction sites,
      is intrinsic to many functional processes in the cell. In this paper, we propose
      a novel method to discover patterns in protein interaction sites. We observed
      from protein interaction networks that there exist a kind of significant
      substructures called interacting protein group pairs, which exhibit an all-versus
      all interaction between the two protein-sets in such a pair. The full-interaction
      between the pair indicates a common interaction mechanism shared by the proteins
      in the pair, which can be referred as an interaction type. Motif pairs at the
      interaction sites of the protein group pairs can be used to represent such
      interaction type, with each motif derived from the sequences of a protein group
      by standard motif discovery algorithms. The systematic discovery of all pairs of
      interacting protein groups from large protein interaction networks is a
      computationally challenging problem. By a careful and sophisticated problem
      transformation, the problem is solved using efficient algorithms for mining
      frequent patterns, a problem extensively studied in data mining. RESULTS: We
      found 5349 pairs of interacting protein groups from a yeast interaction dataset.
      The expected value of sequence identity within the groups is only 7.48%,
      indicating non-homology within these protein groups. We derived 5343 motif pairs
      from these group pairs, represented in the form of blocks. Comparing our motifs
      with domains in the BLOCKS and PRINTS databases, we found that our blocks could
      be mapped to an average of 3.08 correlated blocks in these two databases. The
      mapped blocks occur 4221 out of total 6794 domains (protein groups) in these two
      databases. Comparing our motif pairs with iPfam consisting of 3045 interacting
      domain pairs derived from PDB, we found 47 matches occurring in 105 distinct PDB
      complexes. Comparing with another putative domain interaction database InterDom,
      we found 203 matches. AVAILABILITY: http://research.i2r.a
      star.edu.sg/BindingMotifPairs/resources. SUPPLEMENTARY INFORMATION:
      http://research.i2r.a-star.edu.sg/BindingMotifPairs and Bioinformatics online.

PMID- 16446279
TI  - Capturing expert knowledge with argumentation: a case study in bioinformatics.
AB  - MOTIVATION: The output of a bioinformatic tool such as BLAST must usually be
      interpreted by an expert before reliable conclusions can be drawn. This may be
      based upon the expert's experience, additional data and statistical analysis.
      Often the process is laborious, goes unrecorded and may be biased. Argumentation
      is an established technique for reasoning about situations where absolute truth
      or precise probability is impossible to determine. RESULTS: We demonstrate the
      application of argumentation to 3D-PSSM, a protein structure prediction tool. The
      expert's interpretation of results is represented as an argumentation framework.
      Given a 3D-PSSM result, an automated procedure constructs arguments for and
      against the conclusion that the result is a good predictor of protein structure.
      In addition to capturing the unique expertise of the author of 3D-PSSM for
      distribution to users, an improvement in recall of 5-10 percentage points is
      achieved. This technique can be applied to a wide range of bioinformatic tools.
      AVAILABILITY: Example public server and benchmarking data are available at
      http://www.sbg.bio.ic.ac.uk/~brj03/argumentation/paper/. Source code available on
      request.

PMID- 16446280
TI  - Physical work environment risk factors for long term sickness absence:
      prospective findings among a cohort of 5357 employees in Denmark.
AB  - OBJECTIVES: To examine the effects of physical work environment on long term
      sickness absence and to investigate interaction between physical and psychosocial
      risk factors. DESIGN AND SETTING: Prospective cohort study of long term sickness
      absence among employees in Denmark. PARTICIPANTS: 5357 employees interviewed in
      2000 about their physical work environment, and various covariates were followed
      for 18 months in a national sickness absence register. Outcome measurements Cox
      regression analysis was performed to assess risk estimates for physical risk
      factors in the work environment and onset of long term sickness absence, defined
      as receiving sickness absence compensation for eight consecutive weeks or more.
      RESULTS: 348 participants (6.9%) developed long term sickness absence during
      follow-up. Of these, 194 (55.7%) were women and 154 (44.3%) were men. For both
      female and male employees, risk of onset of long term sickness absence was
      increased by extreme bending or twisting of the neck or back, working mainly
      standing or squatting, lifting or carrying loads, and pushing or pulling loads.
      Significant interactions were found for three combinations of physical and
      psychosocial work environment risk factors among female employees (P<0.05).
      CONCLUSION: Uncomfortable working positions, lifting or carrying loads, and
      pushing or pulling loads increased the risk of onset of long term sickness
      absence. The study shows a potential for reducing long term sickness absence
      through modifying work postures straining the neck and back, reducing the risk of
      work done standing or walking, and reducing the risk associated with handling
      loads. Dealing with psychosocial stressors simultaneously may improve physical
      intervention efforts further for female employees.

PMID- 16446282
TI  - A diet-induced mouse model for glutaric aciduria type I.
AB  - In the autosomal recessive human disease, glutaric aciduria type I (GA-1),
      glutaryl-CoA dehydrogenase (GCDH) deficiency disrupts the mitochondrial
      catabolism of lysine and tryptophan. Affected individuals accumulate glutaric
      acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in the serum and often suffer acute
      striatal injury in childhood. Prior attempts to produce selective striatal
      vulnerability in an animal model have been unsuccessful. We hypothesized that
      acute striatal injury may be induced in GCDH-deficient (Gcdh-/-) mice by elevated
      dietary protein and lysine. Here, we show that high protein diets are lethal to 4
      week-old and 8-week-old Gcdh-/- mice within 2-3 days and 7-8 days, respectively.
      High lysine alone resulted in vasogenic oedema and blood-brain barrier breakdown
      within the striatum, associated with serum and tissue GA accumulation, neuronal
      loss, haemorrhage, paralysis, seizures and death in 75% of 4-week-old Gcdh-/-
      mice after 3-12 days. In contrast, most 8-week-old Gcdh-/- mice survived on high
      lysine, but developed white matter lesions, reactive astrocytes and neuronal loss
      after 6 weeks. Thus, the Gcdh-/- mouse exposed to high protein or lysine may be a
      useful model of human GA-1 including developmentally dependent striatal
      vulnerability.

PMID- 16446281
TI  - Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective
      analysis.
AB  - Experimental prolonged febrile seizures (FS) lead to structural and molecular
      changes that promote hippocampal hyperexcitability and reduce seizure threshold
      to further convulsants. However, whether these seizures provoke later-onset
      epilepsy, as has been suspected in humans, has remained unclear. Previously,
      intermittent EEGs with behavioural observations for motor seizures failed to
      demonstrate spontaneous seizures in adult rats subjected to experimental
      prolonged FS during infancy. Because limbic seizures may be behaviourally subtle,
      here we determined the presence of spontaneous limbic seizures using chronic
      video monitoring with concurrent hippocampal and cortical EEGs, in adult rats
      (starting around 3 months of age) that had sustained experimental FS on postnatal
      day 10. These subjects were compared with groups that had undergone hyperthermia
      but in whom seizures had been prevented (hyperthermic controls), as well as with
      normothermic controls. Only events that fulfilled both EEG and behavioural
      criteria, i.e. electro-clinical events, were considered spontaneous seizures.
      EEGs (over 400 recorded hours) were normal in all normothermic and hyperthermic
      control rats, and none of these animals developed spontaneous seizures. In
      contrast, prolonged early-life FS evoked spontaneous electro-clinical seizures in
      6 out of 17 experimental rats (35.2%). These seizures consisted of sudden
      freezing (altered consciousness) and typical limbic automatisms that were coupled
      with polyspike/sharp-wave trains with increasing amplitude and slowing frequency
      on EEG. In addition, interictal epileptiform discharges were recorded in 15
      (88.2%) of the experimental FS group and in none of the controls. The large
      majority of hippocampally-recorded seizures were heralded by diminished amplitude
      of cortical EEG, that commenced half a minute prior to the hippocampal ictus and
      persisted after seizure termination. This suggests a substantial perturbation of
      normal cortical neuronal activity by these limbic spontaneous seizures. In
      summary, prolonged experimental FS lead to later-onset limbic (temporal lobe)
      epilepsy in a significant proportion of rats, and to interictal epileptifom EEG
      abnormalities in most others, and thus represent a model that may be useful to
      study the relationship between FS and human temporal lobe epilepsy.

PMID- 16446283
TI  - Does gastrostomy tube feeding in children with cerebral palsy increase the risk
      of respiratory morbidity?
AB  - BACKGROUND: Children with severe neurological impairment may have significant
      oral motor dysfunction and are at increased risk of nutritional deficiencies,
      poor growth, and aspiration pneumonia. Gastrostomy tube feeding is increasingly
      being used for nutritional support in these children. AIM: To examine the
      occurrence of respiratory morbidity before and after gastrostomy feeding tube
      insertion in children with severe neurological disabilities. METHODS: This study
      was nested in a longitudinal, prospective, uncontrolled, multicentre cohort study
      designed to investigate the outcomes of gastrostomy tube feeding in 57 children
      with severe neurological disabilities. Parents completed a questionnaire prior to
      (visit 1) and 6 and 12 months (visits 2 and 3) following the gastrostomy,
      detailing number of chest infections requiring antibiotics and/or hospital
      admission. RESULTS: Mean number of chest infections requiring antibiotics was 1.8
      on visit 1 and 0.9 on visit 3. Hospital admissions for chest infections fell
      significantly from 0.5 to 0.09. CONCLUSION: This study provides no evidence for
      an increase in respiratory morbidity following insertion of a feeding gastrostomy
      in children with cerebral palsy.

PMID- 16446284
TI  - A comparative study on the anatomy and development of different shapes of domatia
      in Cinnamomum camphora (Lauraceae).
AB  - BACKGROUND AND AIMS: Domatia are small organs usually found in the axils of major
      veins on the underside of leaves and, although they have received wide attention
      from ecologists, few detailed reports exist on their anatomy or development. This
      study is focused on the domatia of Cinnamomum camphora (Lauraceae) and is the
      first comparative study on the anatomy and development of the different shapes of
      domatia within a single plant. METHODS: Four types of domatia in C. camphora
      leaves were observed on paraffin sections under a microscope. KEY RESULTS: The
      domatia consisted of six histological parts: the upper epidermis, the upper
      mesophyll tissue, spongy tissue, the lower mesophyll tissue, the tissue filling
      the rim opening, and the lower epidermis. They differed from the non-domatial
      lamina mainly in the cell structure of the upper and lower mesophyll tissue and
      the rim tissue. Differences in domatium shapes were mainly associated with
      differences in the structure of the upper mesophyll and in the number and size of
      the rim tissue cells. Differences in the development of domatium types were
      observed in terms of initiation timing, differentiation of the upper mesophyll
      cells and degree of rim tissue development. CONCLUSIONS: In domatia, active
      anticlinal division in the lower mesophyll cells, as compared with the upper
      mesophyll cells, was coordinated with dynamic growth of rim tissue cells and
      resulted in cavity formation. The anatomical or developmental differences among
      the four types of domatia were related to the positions of the domatia within a
      leaf. In terms of the ecological implications, the major anatomical difference
      between the domatia used by herbivorous and carnivorous mites was in the
      development of the rim tissue.

PMID- 16446285
TI  - The genetic diversity of two brazilian vellozia (velloziaceae) with different
      patterns of spatial distribution and pollination biology.
AB  - BACKGROUND AND AIMS: The genetic structure and variability of two species of
      Vellozia (Velloziaceae) with restricted distribution in high-altitude quartzitic
      fields in south-eastern Brazil were studied. Vellozia epidendroides is short,
      grows on pebbly or sandy soil, and is pollinated by bees. Vellozia leptopetala is
      arborescent, grows on rock outcrops, and is pollinated by bees and hummingbirds.
      Both are self-incompatible and have a short, massive flowering strategy. The
      study aimed to associate differences in their genetic diversity and structure
      with their microhabitat distribution and pollination ecology. METHODS: Leaves
      from 106 and 139 plants of V. epidendroides and V. leptopetala, respectively,
      were collected from five patches of each species and prepared for electrophoretic
      analyses. KEY RESULTS: Five enzyme systems could be reliably scored for both
      species. Vellozia epidendroides showed 100 % of the loci polymorphic for almost
      all patches. The average number of alleles per locus ranged between 2.2 and 2.4
      among patches. The Wright's fixation index (F) for this species was 0.226. A
      significant (p) value indicates that there is a reasonable genetic divergence
      among patches. Vellozia leptopetala presented 47.5 % of polymorphic loci. All
      levels of P, A, A(p) and of heterozygosities were lower than those of V.
      epidendroides. Vellozia leptopetala showed high inbreeding within patches.
      CONCLUSIONS: The relatively high values of genetic diversity indices found for V.
      epidendroides may be associated with its large and widespread populations. On the
      other hand, the low values of genetic diversity found for V. leptopetala may be
      related to physical isolation on outcrops and intensive foraging by territorial
      hummingbirds, which may hinder gene flow among patches, aggravated by the very
      restricted seed dispersal characteristic of the genus, that facilitates sibling
      mating. It is important to stress the need to preserve the specific habitats of
      these species of Vellozia, in particular those of V. leptopetala that has lower
      genetic diversity and is restricted to rock outcrop environments.

PMID- 16446288
TI  - Phases of dormancy in Yam tubers (Dioscorea rotundata).
AB  - BACKGROUND AND AIMS: The control of dormancy in yam (Disocorea spp.) tubers is
      poorly understood and attempts to shorten the long dormant period (i.e. cause
      tubers to sprout or germinate much earlier) have been unsuccessful. The aim of
      this study was to identify and define the phases of dormancy in Dioscorea
      rotundata tubers, and to produce a framework within which dormancy can be more
      effectively studied. METHODS: Plants of 'TDr 131' derived from tissue culture
      were grown in a glasshouse simulating temperature and photoperiod at Ibadan (7
      degrees N), Nigeria to produce tubers. Tubers were sampled on four occasions: 30
      d before shoot senescence (149 days after planting, DAP), at shoot senescence
      (179 DAP), and twice during storage at a constant 25 degrees C (269 and 326 DAP).
      The development of the apical shoot bud was described from tissue sections. In
      addition, the responsiveness of shoot apical bud development to plant growth
      regulators (gibberellic acid, 2-chloroethanol and thiourea) applied to excised
      tuber sections was also examined 6 and 12 d after treatment. KEY RESULTS AND
      CONCLUSIONS: Three phases of tuber dormancy are proposed: Phase I, from tuber
      initiation to the appearance of the tuber germinating meristem; Phase II, from
      the tuber germinating meristem to initiation of foliar primordium; and Phase III,
      from foliar primordium to appearance of the shoot bud on the surface of the
      tuber. Phase I is the longest phase (approx. 220 d in 'TDr 131'), is not affected
      by PGRs and is proposed to be an endo-dormant phase. Phases II and III are
      shorter (<70 d in total), are influenced by PGRs and environmental conditions,
      and are therefore endo-/eco-dormant phases. To manipulate dormancy to allow off
      season planting and more than one generation per year requires that the duration
      of Phase I is shortened.

PMID- 16446289
TI  - Proteome analysis of human hair shaft: from protein identification to
      posttranslational modification.
AB  - The human hair proteome was investigated using two-dimensional LC-MS/MS. Among
      the 343 identified proteins, 70 were detected in high relative abundance,
      including keratin intermediate filament proteins, largely extractable with
      denaturants. Over 300 proteins were found to constitute the insoluble complex
      formed by transglutaminase cross-linking. The intracellular distribution of
      identified proteins is wide from cytoplasm to nucleus, mitochondria, ribosome,
      and plasma membrane. These results help rationalize ultrastructural features
      visible in the mature hair. Keratins and several substrates for transglutaminase
      were found to be posttranslationally modified by methylation and dimethylation.
      Evidence for ubiquitination of hair proteins was also obtained.

PMID- 16446291
TI  - Genetic structure and evolutionary history of a diploid hybrid pine Pinus densata
      inferred from the nucleotide variation at seven gene loci.
AB  - Although homoploid hybridization is increasingly recognized as an important
      phenomenon in plant evolution, its evolutionary genetic mechanisms are poorly
      documented and understood. Pinus densata, a pine native to the Tibetan Plateau,
      represents a good example of a homoploid hybrid speciation facilitated by
      adaptation to extreme environment and ecological isolation from the parents. Its
      ecologically and reproductively stabilized nature offers excellent opportunity
      for studying genetic processes associated with hybrid speciation. In this study,
      we investigated the levels and patterns of nucleotide variation in P. densata and
      its putative parents. Haplotype composition, gene genealogies, and the levels and
      patterns of nucleotide variation gave further support to the hybrid nature of P.
      densata. Allelic history, as revealed by our data, suggests the ancient nature of
      the hybrid preceding elevation of the Tibetan Plateau. We detected more
      deviations from neutrality in P. densata than in the parental species. Thus, at
      least some of the evolutionary forces that have shaped the genetic variation in
      P. densata are likely to be different from those acting upon parental species. We
      speculate that when populations of P. densata invaded new territories, they had
      elevated rates of response to selection in order to develop traits that help them
      to survive and adapt in the new environments.

PMID- 16446287
TI  - Effects of Neotyphodium fungi on Lolium multiflorum seed germination in relation
      to water availability.
AB  - BACKGROUND AND AIMS: Temperate endophyte-infected (Neotyphodium sp.) grasses have
      been shown to exhibit an ecological advantage over endophyte-uninfected grasses
      under abiotic stressful conditions. It is predicted that endophyte-infected plant
      populations will display higher rates of germination and proportion of germinated
      seeds under limiting water conditions. METHODS: The hydrotime regression model
      was used to describe the effect of Neotyphodium endophyte on seed germination of
      Lolium multiflorum at different water potentials. Additionally, seed mortality
      after water stress exposure was estimated in endophyte-infected and -uninfected
      seeds. KEY RESULTS: Endophyte infection inhibited seed germination at all water
      potentials. The hydrotime model described satisfactorily the germination
      responses, and revealed that endophyte-free seeds exhibited higher rates of and
      final percentage germination, probably due to a lower base water potential
      compared with endophyte-infected seeds. However, Neotyphodium endophyte conferred
      a higher rate of survival in those seeds that remained ungerminated when exposed
      to highly water stress conditions. CONCLUSIONS: Changes produced by Neotyphodium
      endophyte in L. multiflorum seeds might affect fitness in particular ecological
      scenarios. For example, the presence of the endophyte may curtail seed
      germination when water is limiting, reducing the risk of seedling death.
      Conversely, endophyte-free seeds would display an enhanced germination, ensuring
      a more rapid seedling establishment if later water conditions do not restrict
      plant growth.

PMID- 16446286
TI  - Citrate transporters play a critical role in aluminium-stimulated citrate efflux
      in rice bean (Vigna umbellata) roots.
AB  - BACKGROUND AND AIMS: Aluminium (Al) stimulates the efflux of citrate from apices
      of rice bean (Vigna umbellata) roots. This response is delayed at least 3 h when
      roots are exposed to 50 microm Al, indicating that some inducible processes
      leading to citrate efflux are involved. The physiological bases responsible for
      the delayed response were examined here. METHODS: The effects of several
      antagonists of anion channels and citrate carriers, and of the protein synthesis
      inhibitor, cycloheximide (CHM) on Al-stimulated citrate efflux and/or citrate
      content were examined by high-pressure liquid chromatography (HPLC) or an
      enzymatic method. KEY RESULTS: Both anion channel inhibitors and citrate carrier
      inhibitors can inhibit Al-stimulated citrate efflux, with anthracene-9-carboxylic
      acid (A-9-C, an anion channel inhibitor) and phenylisothiocyanate (PI, a citrate
      carrier inhibitor) the most effective inhibitors. A 6 h pulse of 50 microm Al
      induced a significant increase of citrate content in root apices and release of
      citrate. However, the increase in citrate content preceded the efflux.
      Furthermore, the release of citrate stimulated by the pulse treatment was
      inhibited by both A-9-C and PI, indicating the importance of the citrate carrier
      on the mitochondrial membrane and the anion channel on the plasma membrane for
      the Al-stimulated citrate efflux. CHM (20 microm) also significantly inhibited Al
      stimulated citrate efflux, confirming that de novo protein synthesis is required
      for Al-stimulated citrate efflux. CONCLUSIONS: These results indicate that the
      activation of genes possibly encoding citrate transporters plays a critical role
      in Al-stimulated citrate efflux.

PMID- 16446290
TI  - Methylmercury impairs components of the cholinergic system in captive mink
      (Mustela vison).
AB  - The effects of methylmercury (MeHg) on components of the cholinergic system were
      evaluated in captive mink (Mustela vison). Cholinergic parameters were measured
      in brain regions (occipital cortex, cerebellum, brain stem, basal ganglia) and
      blood (whole blood, plasma, serum) following an 89-day exposure to MeHg at
      dietary concentrations of 0, 0.1, 0.5, 1, and 2 ppm (n = 12 animals per
      treatment). There were no effects of MeHg on brain choline acetyltransferase,
      acetylcholine, and choline transporter. However, significantly higher densities
      of muscarinic cholinergic receptors, as assessed by 3H-quinuclidinyl benzilate
      binding, were measured in the occipital cortex (30.2 and 39.0% higher in the 1
      and 2 ppm groups, respectively), basal ganglia (67.5 and 69.1% higher in the 0.5
      and 1 ppm groups, respectively), and brain stem (64.4% higher in the 0.5 ppm
      group), compared to nonexposed controls. The calculated positive relationship
      between MeHg exposure and muscarinic cholinergic receptor levels in this dosing
      study were consistent with observations in wild mink. There were no MeHg-related
      effects on blood cholinesterase (ChE) activity, but ChE activity was
      significantly higher in the occipital cortex (17.0% in the 1 ppm group) and basal
      ganglia (34.1% in the 0.5 ppm group), compared to nonexposed controls. The
      parallel increases in muscarinic cholinergic receptor levels and ChE activity
      following MeHg exposure highlight the autoregulatory nature of cholinergic
      neurotransmission. In conclusion, these laboratory data support findings from
      wild mink and demonstrate that ecologically relevant exposures to MeHg (i.e., 0.5
      ppm in diet) have the potential to alter the cholinergic system in specific brain
      regions.

PMID- 16446292
TI  - Epilepsy among the homeless: prevalence and characteristics.
AB  - Homelessness is associated with several risk factors for epileptic seizures.
      Epilepsy is a stigmatizing condition, which can lead to problematic social
      adjustment and competence. We found a markedly higher prevalence of seizures
      among the homeless than that estimated in the general population, with a large
      majority of non-alcoholic etiology. Unexpected proportion of subject taking
      treatment and compliance rate call for reflection on the optimal management of
      epilepsy in this population.

PMID- 16446294
TI  - Necessary steps for a modern scientific journal.

PMID- 16446293
TI  - Acceptance of killing and homicide rates in nineteen nations.
AB  - BACKGROUND: International variation in homicide rates may be attributable to
      cultural differences in acceptance of moral justifications for killing. The aim
      of this study is to investigate the relationships between measures of attitudes
      towards the justification of killing and homicide rates in diverse international
      populations. METHODS: Four studies assessed variations in acceptance of killing
      among adults and young people in nineteen nations and four areas in the USA.
      Study 1 (1996-1997) assessed adult attitudes in Brazil, Chile, Costa Rica, Spain,
      and Venezuela with personal interviews in major cities. Study 2 (1999-2001)
      assessed attitudes among high school students in Denmark, Finland, Malta, Mexico,
      Netherlands, Slovenia, Sweden, Taiwan, and the UK with paper surveys administered
      in classrooms. Study 3 (2001) used telephone interviews to measure the equivalent
      attitudes among the US samples nationally and from regions in Texas. Study 4
      (2002-2003) used paper surveys in classrooms to measure attitudes among high
      school students in Armenia, Belarus, Georgia, and the Russian Federation.
      RESULTS: The acceptance of killing varied significantly among genders and
      national/regional groups. The mean attitude scores in the four studies combined
      were significantly correlated with national/regional homicide rates and the
      amount of variance explained was similar to that for social inequality (GINI).
      Together the attitude scores and GINI explained 65% of the variance in homicide
      rates. CONCLUSION: This study provides evidence that variations in attitudes
      toward the justification of killing may be related to international differences
      in homicide rates.

PMID- 16446296
TI  - Trust and the sociology of the professions.

PMID- 16446295
TI  - Cardiovascular disease: putting transition in perspective.

PMID- 16446297
TI  - Trust relations in health care--the new agenda.

PMID- 16446300
TI  - Socioeconomic status and health behaviour patterns through adolescence: results
      from a prospective cohort study in Norway.
AB  - BACKGROUND: In this paper, we investigate cross-sectional and prospective
      relationships between various socioeconomic indicators and different health
      behaviours among boys and girls at ages 13-21, and whether socioeconomic status
      (SES) is related to changes in health behaviour over time. METHODS: The study is
      based on a 10-year, two-generation prospective cohort study of health and
      lifestyle factors among a sample of Norwegian adolescents and their parents. Data
      presented here were collected at the ages of 13 (baseline), 15, 18 and 21.
      Parental and adolescent reports of socioeconomic factors were assessed along with
      a number of health-enhancing and health-compromising behaviours, both as single
      behaviours and as part of health behaviour indices. RESULTS: Relatively few
      significant relationships are observed between parental occupation and
      adolescents' reported health behaviour when the latter is analysed as single
      behaviours. A significant, but weak, social gradient in health-enhancing
      behaviour is observed when measuring health behaviour as composite indices rather
      than single forms of behaviour. This is apparent both when applying parental SES
      variables or adolescents' own educational aspirations as proxy measures of their
      socioeconomic status. CONCLUSION: Future investigations of the presence of a
      social gradient in adolescent health behaviour should focus on composite measures
      of health behaviour. Further research is needed on potential mediating mechanisms
      behind the SES-health behaviour relationships in youth.

PMID- 16446299
TI  - The sociodemographic patterning of health in Estonia, Latvia, Lithuania and
      Finland.
AB  - BACKGROUND: Public health problems in the Baltic countries are typical of Eastern
      European transition economies. A common assumption is that the economic
      transition has been particularly difficult for previously disadvantaged groups,
      and comparative research on the health differences between sociodemographic
      groups in the Baltic countries is therefore needed. This study compared
      associations of health with gender, age, education, level of urbanization and
      marital status in three Baltic countries and Finland. METHODS: The data were
      gathered from cross-sectional postal surveys conducted in 1994, 1996, 1998 and
      2000 on adult populations (aged 20-64 years) in Estonia (n = 5052), Latvia (n =
      4290), Lithuania (n = 7945) and Finland (n = 12796). Three self-reported health
      indicators were used: (i) perceived health, (ii) diagnosed diseases and (iii)
      symptoms. RESULTS: The prevalence of less-than-good perceived health (average,
      rather poor or poor) was higher in the Baltic countries (men 66-56%, women 68
      64%) than in Finland (men 35%, women 31%). The odds ratios (with 95% confidence
      intervals) of less-than-good perceived health among the low educated compared to
      the highly educated in Estonia, Latvia, Lithuania and Finland were 2.03 (1.49
      2.77), 2.00 (1.45-2.76), 2.27 (1.78-2.89) and 1.89 (1.61-2.20) among men, and
      3.32 (2.43-4.55), 2.77 (2.04-3.77), 2.07 (1.61-2.66) and 1.89 (1.63-2.20) among
      women, respectively. Diseases and symptoms were also more common among the lower
      educated men and women in all four countries. However, urbanization and marital
      status were not consistently related to the health indicators. CONCLUSIONS: The
      Baltic countries share a similar sociodemographic patterning of health with most
      European countries, i.e. the lower educated have worse health. The methodological
      considerations of this study point out, however, that further research is needed
      to support public health policies aimed at the most vulnerable population groups.

PMID- 16446301
TI  - Relation between the socioeconomic status of the family and primary allergy
      prevention in infant feeding in Hajdu-Bihar County, Hungary.
AB  - BACKGROUND: The relationship between socioeconomic status and preventive care is
      an important issue in public health practice in Hungary. Our aim was to
      investigate the association between the socioeconomic status and the present
      practice of primary allergy prevention in infant feeding in Hajdu-Bihar County,
      Hungary. METHODS: A questionnaire-based cross-sectional survey was performed
      among 3076 infants aged 0-6 months. We studied how socioeconomic status, type of
      settlement, allergic background of the family and skin symptoms indicative for
      allergy were related to primary allergy prevention in infant feeding. Prevalence
      odds ratios (ORs) were calculated by multiple logistic regression. RESULTS:
      Independent determinants of breast feeding were age [OR corresponding to one
      month change 0.74; 95% confidence interval (CI) 0.70-0.77], the female gender (OR
      1.24; 95% CI 1.06-1.46), the socioeconomic status of the family (OR comparing the
      worst with the best category 0.63; 95% CI 0.43-0.93), and birth weight (OR
      comparing <1500 g to >2500 g category 0.17; 95% CI 0.07-0.41). Among
      supplementary nutrient users independent determinants of the use of hydrolysed
      infant formulae were the socioeconomic status (OR comparing the worst with the
      best category 0.06; 95% CI 0.01-0.27), the type of settlement (OR comparing
      village with town 0.48; 95% CI 0.28-0.80), history of allergy in the family (OR
      2.30; 95% CI 1.28-4.11), and skin symptoms indicative of allergy (OR 3.46; 95% CI
      1.96-6.14). CONCLUSION: Socioeconomic status is related to the implementation of
      primary allergy prevention in infant feeding.

PMID- 16446302
TI  - Neighbourhood non-employment and daily smoking: a population-based study of women
      and men in Sweden.
AB  - BACKGROUND: To examine whether neighbourhood non-employment is associated with
      daily smoking after adjustment for individual characteristics, such as employment
      status. METHODS: Cross-sectional study of a simple, random sample of 31,164 women
      and men aged 25-64, representative of the entire population in Sweden. Data were
      collected from the years 1993-2000. The individual variables included age, sex,
      employment status, occupation and housing tenure. Logistic regression was used in
      the analysis with neighbourhood non-employment rates measured at small area
      market statistics level. RESULTS: There was a significant association between
      neighbourhood non-employment rates and daily smoking for both women and men.
      After adjustment for employment status and housing tenure the odds ratios of
      daily smoking were 1.39 (95% CI = 1.22-1.58) for women and 1.41 (95% CI = 1.23
      1.61) for men living in neighbourhoods with the highest non-employment rates. The
      individual variables of unemployment, low occupational level and renting were
      associated with daily smoking. CONCLUSION: Neighbourhood non-employment is
      associated with daily smoking. Smoking prevention in primary health care should
      address both individuals and neighbourhoods.

PMID- 16446304
TI  - Oxidative stress in mouse brain exposed to lead.
AB  - This study was carried out to investigate effects of developmental Pb-exposure on
      antioxidant enzyme activities of mice brain. BALB dams were exposed to 600 p.p.m.
      of Pb-acetate in drinking water during pregnancy and lactation. Pb-exposure
      presented significant increase of plasma and brain Pb and 5-aminolevulinic acid
      (ALA) concentrations of weaned pups. In Pb-exposed 21-day-old pups, activities of
      superoxide dismutase, glutathione peroxidase (GSH-Px) and glutathione reductase
      (GSH-Re) decreased significantly in hypothalamus, corpora quadrigemina and corpus
      striatum compared with Na-exposed pups. Regarding 70-day-old pups, Pb-exposure
      had different effects on antioxidant enzymes of the three brain regions. The
      activities of GSH-Px and GSH-Re in corpora quadrigemina and GSH-Re in
      hypothalamus of Pb-exposure group did not decrease significantly. That meant that
      the lead employed might make occurrence of long-term effect on the antioxidant
      enzymes possible. The result also implied a correlation between ALA and oxidative
      stress in mice brain. Based on these results, it seemed that oxidative stress
      because of decreased antioxidant function, induced by significant accumulation of
      ALA, might be the main mechanism involved in mice brain neurotoxicity induced by
      developmental Pb-exposure.

PMID- 16446303
TI  - Does qualitative synthesis of anecdotal evidence with that from scientific
      research help in understanding public health issues: a review of low MMR uptake.
AB  - STUDY OBJECTIVE: To explore the professional and parental factors underlying low
      MMR uptake by qualitative synthesis of evidence from technical and non-technical
      anecdotal literature. METHODS: An intensive investigation of literature covering
      research, press, online, E groups and grey literature was carried out using
      devised search strategies. Key themes were identified from both the research and
      anecdotal evidence, which were merged to form common themes. RESULTS: The review
      of technical literature identified media scare and inadequate information from
      health professionals as the main reasons for non-uptake of MMR. The non-technical
      anecdotal evidence showed that professionals' belief in parental right to choose,
      target payments and fear of autism were the major factors. CONCLUSIONS: Anecdotal
      evidence may contribute to evidence-based public health practice, especially in
      widely debated public health issues.

PMID- 16446305
TI  - Mixed models and empirical bayes estimation for retrospective exposure assessment
      of dust exposures in Canadian sawmills.
AB  - OBJECTIVES: Data on job histories is commonly available from study subjects and
      worksites, therefore jobs are often used for assigning exposures in historical
      epidemiological studies. Exposure estimates are often derived by offering jobs as
      fixed effects in statistical models. An alternative approach would be to offer
      job as a random effect to obtain empirical Bayes estimates of exposure. This
      approach is more efficient since it weights exposure estimates according to the
      within-job and between-job variability and the number of measurements for each
      job. We assess three models for predicting historical dust exposures of sawmill
      workers. METHODS: Models were developed using 407 inhalable dust measurements
      collected from 58 jobs in four sawmills. The first model incorporated all
      variables as fixed effects; the second added a random term to account for
      correlation within workers; and the third offered random terms for worker, job
      and mill (hierarchical model). Empirical Bayes estimates were used to calculate
      job-specific exposures from the hierarchical model. RESULTS: The fixed effects
      and random worker mixed models performed nearly identically because there was low
      within-worker correlation (r = 0.26). The Bayesian exposure predictions from the
      hierarchical model were slightly more correlated with the observed mill-job
      arithmetic means than those from the models where jobs were fixed effects (0.74
      versus 0.70). CONCLUSIONS: While we observed no large differences in exposure
      estimates by treating job as a fixed or random effect, treating job as a random
      effect allowed for job-specific coefficients to be estimated for every job while
      borrowing strength in the presence of sparse data by assuming that the job means
      are normally distributed around the group mean. In addition, empirical Bayes job
      estimates can be used for a posteriori job grouping. The use of this method for
      retrospective exposure assessment should continue to be examined.

PMID- 16446307
TI  - Acquisition of the wobble modification in mitochondrial tRNALeu(CUN) bearing the
      G12300A mutation suppresses the MELAS molecular defect.
AB  - The A3243G mutation in the mitochondrial gene for human mitochondrial (mt)
      tRNA(Leu(UUR)), responsible for decoding of UUR codons, is associated with
      mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
      (MELAS). We previously demonstrated that this mutation causes defects in 5
      taurinomethyluridine (taum(5)U) modification at the anticodon first (wobble)
      position of the mutant mt tRNA(Leu(UUR)), leading to a UUG decoding deficiency
      and entraining severe respiratory defects. In addition, we previously identified
      a heteroplasmic mutation, G12300A, in the other mt leucine tRNA gene, mt
      tRNA(Leu(CUN)), which functions as a suppressor of the A3243G respiratory defect
      in cybrid cells containing A3243G mutant mtDNA. Although the G12300A mutation
      converts the anticodon sequence of mt tRNA(Leu(CUN)) from UAG to UAA, this tRNA
      carrying an unmodified wobble uridine still cannot decode the UUG codon. Mass
      spectrometric analysis of the suppressor mt tRNA(Leu(CUN)) carrying the G12300A
      mutation from the phenotypically revertant cells revealed that the wobble uridine
      acquires de novo taum(5)U modification. In vitro translation confirmed the
      functionality of the suppressor tRNA for decoding UUG codons. These results
      demonstrate that the acquisition of the wobble modification in another
      isoacceptor tRNA is critical for suppressing the MELAS mutation, and they
      highlight the primary role of the UUG decoding deficiency in the molecular
      pathogenesis of MELAS syndrome.

PMID- 16446308
TI  - Genomic and functional profiling of duplicated chromosome 15 cell lines reveal
      regulatory alterations in UBE3A-associated ubiquitin-proteasome pathway
      processes.
AB  - Autism is a complex neurodevelopmental disorder having both genetic and
      epigenetic etiological elements. Isodicentric chromosome 15 (Idic15),
      characterized by duplications of the multi-disorder critical region of 15q11-q14,
      is a relatively common cytogenetic event. When the duplication involves
      maternally derived content, this abnormality is strongly correlated with autism
      disorder. However, the mechanistic links between Idic15 and autism are ill
      defined. To gain insight into the potential role of these duplications, we
      performed a comprehensive, genomics-based characterization of an in vitro model
      system consisting of lymphoblast cell lines derived from individuals with both
      autism and Idic15. Array-based comparative genomic hybridization using commercial
      single nucleotide polymorphism arrays was conducted and found to be capable of
      sub-classifying Idic15 samples by virtue of the lengths of the duplicated
      chromosomal region. In further analysis, whole-genome expression profiling
      revealed that 112 transcripts were significantly dysregulated in samples
      harboring duplications. Paramount among changing genes was ubiquitin protein
      ligase E3A (UBE3A; 15q11-q13), which was found to be nearly 1.5-2.0-fold up
      regulated in duplicated samples at both the RNA and protein levels. Other key
      findings from gene expression analysis included two down-regulated genes, APP and
      SUMO1, with well-characterized roles in the process of apoptosis. We further
      demonstrate in this lymphoblast model that the gene-dosage directed increases in
      UBE3A levels can lead to dysregulation of the process of ubiquitination in
      response to genotoxic insult. This study provides insight into the direct and
      indirect effects of copy number gains in chromosome 15 and provides a framework
      for the study of these effects in neuronal systems.

PMID- 16446310
TI  - A role for Brca1 in chromosome end maintenance.
AB  - The role of BRCA1 in breast and ovarian tumor suppression has been primarily
      ascribed to the maintenance of genome integrity. BRCA1 interacts with components
      of the non-homologous end-joining pathway previously shown to play a role in
      telomere maintenance in yeast. Here, we provide evidence that links Brca1 with
      telomere integrity. Brca1(-/-) T-cells display telomere dysfunction in both loss
      of telomere repeats as well as defective telomere capping. Loss of Brca1
      synergizes with p53 deficiency in the onset and frequency of tumorigenesis.
      Karyotyping of tBrca1(-/-)p53(-/-) thymic lymphomas revealed the presence of
      telomere dysfunction accompanied by clonal chromosomal translocations. The
      telomere dysfunction phenotype in Brca1-deficient cells suggests that loss of
      telomere integrity might contribute to chromosome end dysfunction and permit the
      formation of potentially oncogenic translocations.

PMID- 16446309
TI  - Development and characterization of a hypomorphic Smith-Lemli-Opitz syndrome
      mouse model and efficacy of simvastatin therapy.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a genetic syndrome caused by mutations in
      the 3beta-hydroxysterol Delta(7)-reductase gene (DHCR7). SLOS patients have
      decreased cholesterol and increased 7-dehydrocholesterol (7-DHC) levels. Dietary
      cholesterol supplementation improves systemic biochemical abnormalities; however,
      because of the blood-brain barrier, the central nervous system (CNS) is not
      treated. Simvastatin therapy has been proposed as a means to treat the CNS. Mice
      homozygous for a null disruption of Dhcr7, Dhcr7(Delta3-5/Delta3-5), die soon
      after birth, thus they cannot be used to study postnatal development or therapy.
      To circumvent this problem, we produced a hypomorphic SLOS mouse model by
      introducing a mutation corresponding to DHCR7(T93M). Both Dhcr7(T93M/T93M) and
      Dhcr7(Delta3-5/T93M) mice are viable. Phenotypic findings in Dhcr7(T93M/Delta3-5)
      mice include CNS ventricular dilatation and two to three syndactyly.
      Biochemically, both Dhcr7(T93M/T93M) and Dhcr7(T93M/Delta3-5) mice have elevated
      tissue 7-DHC levels; however, the biochemical defect improved with age. This has
      not been observed in human patients, and is due to elevated Dhcr7 expression in
      mouse tissues. Dietary cholesterol therapy improved sterol profiles in
      peripheral, but not CNS tissues. However, treatment of Dhcr7(T93M/Delta3-5) mice
      with simvastatin decreased 7-DHC levels in both peripheral and brain tissues.
      Expression of Dhcr7 increased in Dhcr7(T93M/Delta3-5) tissues after simvastatin
      therapy, consistent with the hypothesis that simvastatin therapy improves the
      biochemical phenotype by increasing the expression of a Dhcr7 allele with
      residual enzymatic activity. We conclude that simvastatin treatment is
      efficacious in improving the SLOS-associated sterol abnormality found in the
      brain, and thus has the potential to be an effective therapeutic intervention for
      behavioral and learning problems associated with SLOS.

PMID- 16446311
TI  - Isolation and characterization of a novel peroxidase gene ZPO-C whose expression
      and function are closely associated with lignification during tracheary element
      differentiation.
AB  - In an attempt to elucidate the regulatory mechanism of vessel lignification, we
      isolated ZPO-C, a novel peroxidase gene of Zinnia elegans that is expressed
      specifically in differentiating tracheary elements (TEs). The ZPO-C transcript
      was shown to accumulate transiently at the time of secondary wall thickening of
      TEs in xylogenic culture of Zinnia cells. In situ hybridization indicated
      specific accumulation of the ZPO-C transcript in immature vessels in Zinnia
      seedlings. Immunohistochemical analysis using anti-ZPO-C antibody showed that the
      ZPO-C protein is abundant in TEs, especially at their secondary walls. For
      enzymatic characterization of ZPO-C, 6 x His-tagged ZPO-C was produced in tobacco
      cultured cells and purified. The ZPO-C:6 x His protein had a peroxidase activity
      preferring sinapyl alcohol as well as coniferyl alcohol as a substrate, with a
      narrow pH optimum around 5.25. The peroxidase activity required calcium ion and
      was elevated by increasing Ca2+ concentration in the range of 0-10 mM. An
      Arabidopsis homolog of ZPO-C, At5g51890, was examined for expression patterns
      with transgenic plants carrying a yellow fluorescent protein (YFP) gene under the
      control of the At5g51890 promoter. The YFP fluorescence localization demonstrated
      vessel-specific expression of At5g51890 in the Arabidopsis roots. Taken
      collectively, our results strongly suggest that ZPO-C and its homologs play an
      important role in lignification of secondary cell walls in differentiating TEs.

PMID- 16446312
TI  - Isolation of cDNAs for R2R3-MYB, bHLH and WDR transcriptional regulators and
      identification of c and ca mutations conferring white flowers in the Japanese
      morning glory.
AB  - The transcriptional regulators for anthocyanin biosynthesis include members of
      proteins containing an R2R3-MYB domain, a bHLH (basic helix-loop-helix) domain
      and conserved WD40 repeats (WDRs). Spacial and temporal expression of the
      structural genes encoding the enzymes for anthocyanin biosynthesis is thought to
      be determined by combinations of the R2R3-MYB, bHLH and WDR factors and their
      interactions. While the wild-type Japanese morning glory (Ipomoea nil) exhibits
      blue flowers with colored stems and dark-brown seeds, the c mutants display white
      flowers with red stems and colored seeds, and the ca mutants exhibit white
      flowers with green stems and ivory seeds. Here, we characterize the tissue
      specific expression of three MYB genes, three bHLH genes and two WDR genes in I.
      nil. We also show that the recessive c-1 and ca alleles are frameshift mutations
      caused by a 2 bp deletion and 7 bp insertions in the genes for the R2R3-MYB and
      WDR transcriptional regulators designated as InMYB1 and InWDR1, respectively. In
      addition to defects in flower, stem and seed pigmentations, the ca mutants were
      found to show reduced trichome formation in seeds but to produce leaf and stem
      trichomes and root hairs normally. Except for the gene for chalcone synthase E in
      the ca mutant, all structural genes tested were coordinately reduced in both c-1
      and ca mutant flower limbs. However, slight but significant expression of the
      genes for chalcone synthase D, chalcone isomerase and flavanone 3-hydroxylase in
      the pathway for flavonol biosynthesis was detectable in c-1 and ca mutants,
      whereas no such residual expression could be observed in other genes involved in
      the later anthocyanin biosynthesis pathway. The biological roles of the C-1 and
      Ca genes in I. nil epidermal traits and their evolutionary implications are also
      discussed.

PMID- 16446313
TI  - Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled
      trial.
AB  - In chronic obstructive pulmonary disease (COPD), the sympathetic nervous system,
      as well as the renin-angiotensin system, is activated with possible negative
      systemic effects on skeletal muscles. Angiotensin II type-1 receptor blockers
      inhibit the sympathetic and renin-angiotensin systems and might improve skeletal
      and respiratory muscle strength in patients in whom these systems are activated.
      The effects of the angiotensin receptor blocker irbesartan given over 4 months
      was evaluated in 60 patients with COPD and a forced expiratory volume in one
      second of <50% of the predicted value and without obvious cardiovascular disease
      that would necessitate the administration of an angiotensin-converting enzyme
      inhibitor or an angiotensin receptor blocker. Irbesartan was well tolerated, but
      did not exert a significant effect on the primary end-point maximum inspiratory
      pressure. Spirometric results were not affected, but total lung capacity was
      reduced. Irbesartan led to a significant decrease in haematocrit (46.4+/-3.6 to
      43.9+/-4.3% versus 47.5+/-2.4 to 48.7+/-3.0% with placebo). In conclusion,
      respiratory muscle strength in chronic obstructive pulmonary disease patients was
      not influenced by angiotensin II receptor blockade. However, the changes in
      haematocrit and total lung capacity following irbesartan raise the possibility
      that well-known cardiovascular drugs can produce unanticipated beneficial effects
      in chronic obstructive pulmonary disease patients.

PMID- 16446314
TI  - Alveolar nitric oxide versus measures of peripheral airway dysfunction in severe
      asthma.
AB  - Alveolar nitric oxide (NO) is a measure of peripheral airway inflammation in
      asthma, potentially associated with disease severity. The relationship between
      alveolar NO and physiological tests of peripheral airway (dys)function has not
      been investigated. The present authors hypothesised that peripheral airway
      inflammation and dysfunction are inter-related and associated with asthma
      severity. Alveolar NO was compared between 17 patients with mild-to-moderate
      asthma and 14 patients with severe asthma and related to total lung capacity
      (TLC), residual volume (RV)/TLC, thoracic gas volume (FRC), slope of the single
      breath nitrogen washout curve (dN2), closing capacity (CC)/TLC and fall in forced
      vital capacity at the provocative concentration of methacholine causing a 20%
      fall in forced expiratory volume in one second. In patients with severe asthma,
      strong correlations were found between alveolar NO and RV/TLC % pred, FRC % pred,
      dN2, and CC/TLC. Patients with oral steroid-dependent asthma had higher alveolar
      NO levels (2.7 ppb) compared with the other patients with severe (0.6 ppb) and
      mild-to-moderate asthma (0.3 ppb). The present authors conclude that alveolar
      nitric oxide is closely related to parameters of peripheral airway dysfunction in
      patients with severe asthma, and that oral steroid-dependent asthmatics have more
      peripheral airway disease than nonsteroid-dependent asthmatics. This suggests
      that patients on chronic oral steroid treatment have more extensive disease and
      require additional anti-inflammatory treatment to better target the peripheral
      airways.

PMID- 16446315
TI  - Noninvasive detection of expiratory flow limitation in COPD patients during nasal
      CPAP.
AB  - The difference between mean inspiratory and expiratory respiratory reactance
      (delta(rs)) measured with forced oscillation technique (FOT) at 5 Hz allows the
      detection of expiratory flow limitation (EFL) in chronic obstructive pulmonary
      disease (COPD) patients breathing spontaneously. This aim of this study was to
      evaluate whether this approach can be applied to COPD patients during noninvasive
      pressure support. Delta(rs) was measured in seven COPD patients subjected to
      nasal continuous positive airway pressure (CPAP) at 0, 4, 8 and 12 cmH2O in
      sitting and supine positions. Simultaneous recording of oesophageal pressure and
      the Mead and Whittenberger (M-W) method provided a reference for scoring each
      breath as flow-limited (FL), non-flow-limited (NFL) or indeterminate (I). For
      each patient, six consecutive breaths were analysed for each posture and CPAP
      level. According to M-W scoring, 47 breaths were FL, 166 NFL and 51 I. EFL
      scoring using FOT coincided with M-W in 94.8% of the breaths. In the four
      patients who were FL in at least one condition, delta(rs) was reduced with
      increasing CPAP. These data suggest that the forced oscillation technique may be
      useful in chronic obstructive pulmonary disease patients on nasal pressure
      support by identifying continuous positive airway pressure levels that support
      breathing without increasing lung volume, which in turn increase the work of
      breathing and reduce muscle effectiveness and efficiency.

PMID- 16446316
TI  - Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment.
AB  - The role of inhaled corticosteroids in the management of chronic obstructive
      pulmonary disease (COPD) remains controversial. The purpose of this study was to
      evaluate whether sputum eosinophilia (defined as eosinophils > or = 3%) predicts
      clinical benefit from inhaled corticosteroid treatment in patients with smoking
      related clinically stable moderate-to-severe COPD. Forty consecutive patients
      with effort dyspnoea (mean age 67 yrs; 52 pack-yr smoking history; post
      bronchodilator forced expiratory volume in one second (FEV1) <60% predicted,
      consistent with moderate-to-severe smoking-related chronic airflow limitation)
      were enrolled. Subjects were treated with inhaled placebo followed by inhaled
      budesonide (Pulmicort Turbuhaler 1,600 microg.day(-1)), each given for 4 weeks.
      While the treatment was single-blind (subject level), sputum cell counts before
      and after treatment interventions were double-blind, thus removing bias. Outcome
      variables included spirometry, quality-of-life assessment and 6-min walk test.
      Sputum eosinophilia was present in 38% of subjects. In these, budesonide
      treatment normalised the eosinophil counts and, in comparison to placebo
      treatment, resulted in clinically significant improvement in the dyspnoea domain
      of the disease-specific chronic respiratory questionnaire (0.8 versus 0.3) and a
      small but statistically significant improvement in post-bronchodilator spirometry
      (FEV1 100 mL versus 0 mL; p<0.05). In conclusion, sputum eosinophilia predicts
      short-term clinical benefit from high-dose inhaled corticosteroid treatment in
      patients with stable moderate-to-severe chronic obstructive pulmonary disease.

PMID- 16446317
TI  - The role of dose size in a chemotherapy regimen (ProMECE-CytaBOM) for the first
      line treatment of large B-cell lymphomas: a randomized trial by the Gruppo
      Italiano Studio Linfomi (GISL).
AB  - BACKGROUND: It is still unclear the actual contribute of dose intensity (DI),
      dose size (DS) and dose density (DD) in the conventional chemotherapy of large, B
      cell non-Hodgkin lymphomas. METHODS: A prospective, randomized trial compared the
      cyclic schedule of ProMECE-CytaBOM chemotherapy (cyc-PC, 6 cycles) with a
      modified version of it, which administered the same drugs sequentially (seq-PC),
      with the same planned cumulative DI and an 83% DD, within the same time frame
      (113 days), but with three times higher DS of all the drugs except vincristine.
      RESULTS: Fifty-six patients received cyc-PC and 52 seq-PC. The actual mean
      cumulative DI was 0.79 +/- 0.15 with cyc-PC, 0.78 +/- 0.17 with seq-PC. Response
      was complete in 59% and 52%, partial in 20% and 21%, null in 5% and 6%,
      respectively. There were four toxic deaths (two per arm). Relapses occurred in
      36% and 37%, respectively. Toxicity was similar in both arms. Overall, failure
      free, progression-free and disease-free survival (median follow-up: 54 months)
      were statistically indifferent. CONCLUSIONS: The very similar DI actually
      delivered in both arm seems to be the main common determinant of the indifferent
      results recorded. Increasing DS--at least within the limits clinically attainable
      without stem cell rescue--does not improve results.

PMID- 16446318
TI  - Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer.
AB  - BACKGROUND: High-dose chemotherapy in the adjuvant treatment of breast cancer has
      been abandoned by many. PATIENTS AND METHODS: 885 patients with stage III primary
      breast cancer and four or more axillary lymph node metastases were randomised to
      receive either five courses of FEC (fluorouracil, epirubicin and
      cyclophosphamide) followed by radiation therapy and tamoxifen, or the same
      treatment but with high-dose alkylating chemotherapy (cyclophosphamide, thiotepa
      and carboplatin) replacing the fifth course of FEC. Of these patients, 621 had
      HER2/neu-negative disease, as determined by immunohistochemistry and chromogenic
      in situ hybridisation. RESULTS: At a median follow-up of 84 months, a trend for a
      better relapse-free survival was observed in the high-dose arm: (hazard ratio
      (HR) 0.84, P = 0.076, two-sided). The 621 patients with HER2/neu-negative disease
      benefited from high-dose therapy, while patients with HER2/neu-positive disease
      did not (test for interaction, P = 0.006). There was a marked relapse-free
      survival benefit for patients with HER2/neu-negative disease (71.5% versus 59.1%,
      5 years after randomisation; HR 0.68, P = 0.002) and also a survival benefit
      (78.2% versus 71.0% at 5 years; HR 0.72, P = 0.02). CONCLUSIONS: The findings
      from this subgroup analysis provide additional evidence that HER2/neu-positive
      breast cancer is relatively resistant to alkylating agents. For HER2/neu-negative
      tumours, however, high-dose chemotherapy should remain the subject of clinical
      studies.

PMID- 16446319
TI  - Spermatogonial stem cells: questions, models and perspectives.
AB  - This review looks into the phylogeny of spermatogonial stem cells and describes
      their basic biological features. We are focusing on species-specific differences
      of spermatogonial stem cell physiology. We propose revised models for the clonal
      expansion of spermatogonia and for the potential existence of true stem cells and
      progenitors in primates but not in rodents. We create a new model for the species
      specific arrangements of spermatogenic stages which may depend on the variable
      clonal expansion patterns. We also provide a brief overview of germ cell
      transplantation as a powerful tool for basic research and its potential use in a
      clinical setting.

PMID- 16446321
TI  - Angiogenesis inhibitors and hypertension: an emerging issue.

PMID- 16446320
TI  - Pregnancy among patients with chronic myeloid leukemia treated with imatinib.
AB  - PURPOSE: Imatinib has potential teratogenicity in animals, but the effect of
      exposure to imatinib during conception and pregnancy in humans is not known.
      PATIENTS AND METHODS: The records of all patients with chronic myeloid leukemia
      (CML) treated with imatinib were reviewed. We report the experience on 19
      pregnancies involving 18 patients (10 females and eight males) who conceived
      while receiving imatinib for the treatment of CML. RESULTS: All female patients
      discontinued therapy immediately on recognition of pregnancy. Three pregnancies
      (involving two female patients and one male patient) ended in spontaneous
      abortion, and one patient had an elective abortion. All other pregnancies were
      uneventful. Two of the 16 babies had minor abnormalities at or shortly after
      birth (hypospadias in one baby and rotation of small intestine in one baby) that
      were surgically repaired. All babies have continued normal growth and
      development. Among female patients who interrupted therapy, five of nine in
      complete hematologic remission (CHR) at the time of treatment interruption
      eventually lost CHR, and six experienced an increase in Philadelphia chromosome
      positive metaphases. At a median of 18 months after resuming therapy with
      imatinib, eight patients had a cytogenetic response (complete in three patients).
      CONCLUSION: Although there is no evidence that a brief exposure to imatinib
      during conception and pregnancy adversely affects the developing fetus, most
      patients lose their response after treatment interruption. Patients receiving
      imatinib should be advised to practice adequate contraception.

PMID- 16446323
TI  - Mechanisms of hypertension associated with BAY 43-9006.
AB  - PURPOSE: BAY 43-9006 (sorafenib) is an inhibitor of Raf kinase, the vascular
      endothelial growth factor (VEGF) receptor-2, and angiogenesis in tumor
      xenografts. The current study investigated the incidence, severity, and mechanism
      of blood pressure (BP) elevation in patients treated with BAY 43-9006. PATIENTS
      AND METHODS: Twenty patients received BAY 43-9006 400 mg orally twice daily. BP
      and heart rate were measured at baseline and then every 3 weeks for 18 weeks.
      VEGF, catecholamines, endothelin I, urotensin II, renin, and aldosterone were
      measured at baseline and after 3 weeks of therapy. We assessed vascular stiffness
      at baseline, after 3 to 6 weeks of therapy, and again after 9 to 10 months of
      therapy. RESULTS: Fifteen (75%) of 20 patients experienced an increase of > or =
      10 mmHg in systolic BP (SBP), and 12 (60%) of 20 patients experienced an increase
      of > or = 20 mmHg in SBP compared with their baseline value, with a mean change
      of 20.6 mmHg (P < .0001) after 3 weeks of therapy. There were no statistically
      significant changes in humoral factors, although there was a statistically
      significant inverse relationship between decreases in catecholamines and
      increases in SBP, suggesting a secondary response to BP elevation. Measures of
      vascular stiffness increased significantly during the period of observation.
      CONCLUSION: Treatment with BAY 43-9006 is associated with a significant and
      sustained increase in BP. The lack of significant change in circulating factors
      suggests that these humoral factors had little role in the increase in BP.

PMID- 16446322
TI  - Short-term treatment-related symptoms and quality of life: results from an
      international randomized phase III study of cisplatin with or without raltitrexed
      in patients with malignant pleural mesothelioma: an EORTC Lung-Cancer Group and
      National Cancer Institute, Canada, Intergroup Study.
AB  - PURPOSE: For malignant pleural mesothelioma (MPM) patients with a poor prognosis,
      maintaining health-related quality of life (HRQOL) is important. This article
      compares the impact on HRQOL of first-line treatment with cisplatin versus
      raltitrexed and cisplatin. PATIENTS AND METHODS: Patients with histologically
      proven unresectable MPM, not pretreated with chemotherapy were randomly assigned
      to receive cisplatin 80 mg/m2 intravenously on day 1, with or without preceding
      infusion of raltitrexed 3 mg/m2. HRQOL was assessed with the European
      Organisation for Research and Treatment of Cancer Core Quality of Life
      Questionnaire C30 (EORTC QLQ-C30) and EORTC Lung Cancer Module (QLQ-LC13) tools.
      Assessments were conducted at baseline, immediately before every treatment cycle,
      at the end of treatment, and every six weeks for 12 months. RESULTS: Two hundred
      fifty patients were randomly assigned, 80% were male with a median age of 58
      years, WHO performance status 0, 1, and 2, in 25%, 62%, and 13% of cases. The
      clinical results found raltitrexed and cisplatin to be superior to cisplatin with
      regard to overall survival (P = .048). The global HRQOL scale was comparable at
      baseline on both treatment arms (P = .848); at no point was any significant
      difference apparent on this end point. Both treatments led to an improvement,
      over time, in dyspnoea. This effect is an important clinically meaningful
      reduction from baseline in the cisplatin/raltitrexed arm. However, the majority
      of scales of the EORTC QLQ-C30 or LC13 showed stabilization of HRQOL with few
      clinically significant differences between the treatment arms. CONCLUSION: This
      study provides important information about the HRQOL of chemotherapy-treated MPM
      patients.

PMID- 16446324
TI  - First case of an AIDS patient with systemic mast cell disease associated with
      FIP1-positive eosinophilia treated with imatinib mesylate therapy.

PMID- 16446325
TI  - Consolidation for ovarian cancer in remission.

PMID- 16446326
TI  - Don't throw out the baby with the bathwater: on optimizing cure and reducing
      toxicity in Hodgkin's lymphoma.

PMID- 16446327
TI  - Preoperative chemotherapy and split-course radiation therapy for patients with
      localized soft tissue sarcomas: home run, base hit, or strike out?

PMID- 16446328
TI  - Cefixime allows greater dose escalation of oral irinotecan: a phase I study in
      pediatric patients with refractory solid tumors.
AB  - PURPOSE: Irinotecan is active against a variety of malignancies; however, severe
      diarrhea limits its usefulness. In our phase I study, the intravenous formulation
      of irinotecan was administered orally daily for 5 days for 2 consecutive weeks
      (repeated every 21 days) to children with refractory solid tumors. Our objectives
      were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and
      pharmacokinetics of oral irinotecan and to evaluate whether coadministration of
      cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout
      the course) ameliorates irinotecan-induced diarrhea. PATIENTS AND METHODS: In
      separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m2/d without
      cefixime and then from 45 to 60 and 75 mg/m2/d with cefixime. RESULTS: Without
      cefixime, diarrhea was dose limiting at irinotecan 45 mg/m2/d. Myelotoxicity was
      not significant at any dose. The MTD was 40 mg/m2/d without cefixime but 60
      mg/m2/d with cefixime. Systemic exposure to SN-38 at the MTD was significantly
      higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5
      ng x h/mL; standard deviation [SD], 6.8 ng x h/mL v 10.4 ng x h/mL; SD, 4.3 ng x
      h/mL, respectively; P = .030). CONCLUSION: Cefixime administered with oral
      irinotecan is well tolerated in children and allows greater dose escalation of
      irinotecan. Because diarrhea is a major adverse effect of both intravenous and
      oral irinotecan, further evaluation of the use of cefixime to ameliorate this
      adverse effect is warranted.

PMID- 16446330
TI  - Randomized study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian
      Cancer Study Group comparing quality of life in patients with ovarian cancer
      treated with cisplatin/paclitaxel versus carboplatin/paclitaxel.
AB  - PURPOSE: The objective of this study was to compare the quality of life (QoL) of
      ovarian cancer patients treated with paclitaxel/carboplatin (TC) versus
      paclitaxel/cisplatin (PT) and to determine the impact of treatment toxicity on
      the various QoL domains. PATIENTS AND METHODS: In this phase III trial, 798
      patients with ovarian cancer stages IIB-IV were randomly assigned to receive TC
      or PT. The primary end point was progression-free survival; secondary end points
      included toxicity, QoL, and response to treatment. Patients completed the
      European Organisation for Research and Treatment of Cancer QLQ-C30 before
      treatment, within 3 days before the second and the fourth chemotherapy cycle, and
      3 weeks after completion of chemotherapy. RESULTS: Previously reported data
      showed that patients undergoing TC or PT did not differ in progression-free
      survival and overall survival. However, the TC arm was superior, indicating a
      better overall QoL compared with the PT arm. Controlling for toxicity and age, a
      significant treatment by assessment time interaction was found for four QoL
      functioning scales and three symptoms scales. Patients in the TC arm showed
      better means scores after treatment on overall QoL (P = .012), physical
      functioning (P = .012), role functioning (P = .005), and cognitive functioning (P
      = .024), compared with the PT arm. Concerning symptom experience, patients
      undergoing TC showed less nausea and vomiting (P < .001), less appetite loss (P <
      .001), and less fatigue (P = .033) after completion of treatment compared with
      patients undergoing PT. CONCLUSION: The TC regimen achieved better QoL outcomes
      compared with the PT regimen. Thus, clinicians may consider replacing cisplatin
      with carboplatin when treating ovarian cancer patients with chemotherapy.

PMID- 16446329
TI  - Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine
      monoclonal antibody in patients with epithelial ovarian cancer after a surgically
      defined complete remission.
AB  - PURPOSE: This was a multinational, open-label, randomized phase III trial
      comparing yttrium-90-labeled murine HMFG1 (90Y-muHMFG1) plus standard treatment
      versus standard treatment alone in patients with epithelial ovarian cancer (EOC)
      who had attained a complete clinical remission after cytoreductive surgery and
      platinum-based chemotherapy. PATIENTS AND METHODS: In total, 844 International
      Federation of Gynecology and Obstetrics stage Ic to IV patients were initially
      screened, of whom 447 patients with a negative second-look laparoscopy (SLL) were
      randomly assigned to receive either a single dose of 90Y-muHMFG1 plus standard
      treatment (224 patients) or standard treatment alone (223 patients). Patients in
      the active treatment arm received a single intraperitoneal dose of 25 mg of 90Y
      muHMFG1 (target dose 666 MBq/m2). The primary end point was length of survival;
      secondary end points included time to relapse and safety. The study had an 80%
      power to detect a 15% change in survival. RESULTS: After a median follow-up of
      3.5 years (range, 1 to 6 years), 70 patients had died in the active treatment arm
      compared with 61 patients in the control arm. Cox proportional hazards analysis
      of survival demonstrated no difference between treatment arms. In the study drug
      arm, 104 patients experienced relapse compared with 98 patients in the standard
      treatment arm. No difference in time to relapse was observed between the two
      study arms. Active therapy was associated with occasional grade 3 or 4
      thrombocytopenia and neutropenia and grade 1 or 2 GI symptoms, abdominal
      discomfort, arthralgia, and myalgia. CONCLUSION A single IP administration of 90Y
      muHMFG1 to patients with EOC who had a negative SLL after primary therapy did not
      extend survival or time to relapse.

PMID- 16446331
TI  - Randomized double-blind trial of estrogen replacement therapy versus placebo in
      stage I or II endometrial cancer: a Gynecologic Oncology Group Study.
AB  - PURPOSE: To determine the effect of estrogen replacement therapy (ERT) on
      recurrence rate and survival in women who have undergone surgery for stage I or
      II endometrial cancer. PATIENTS AND METHODS: After surgery, eligible patients
      were allocated to therapy with ERT or placebo after undergoing hysterectomy with
      or without pelvic and aortic nodal sampling. Planned duration of hormonal versus
      placebo treatment was 3 years, with an additional 2 years of follow-up. RESULTS:
      The median follow-up time for all 1,236 eligible and assessable patients was 35.7
      months. Stage, grade, histologic subtype, and percentage of patients receiving
      adjuvant therapy were similarly distributed between the groups. The median age at
      diagnosis for the 618 patients randomly assigned to ERT was 57 years (range, 26
      to 91 years). Two hundred fifty-one patients (41.1%) were compliant with ERT for
      the entire treatment period. Disease recurrence was experienced in 14 patients
      (2.3%). Eight patients (1.3%) developed a new malignancy. There were 26 deaths
      (4.2%), and five deaths (0.8%) were a result of endometrial cancer. The median
      age at diagnosis for the 618 patients in the placebo group was 57 years (range,
      30 to 88 years). Twelve patients (1.9%) experienced disease recurrence. Ten
      patients (1.6%) developed a new malignancy. There were 9 deaths (3.1%) in the
      placebo group, and four deaths (0.6%) were a result of endometrial cancer.
      CONCLUSION: Although this incomplete study cannot conclusively refute or support
      the safety of exogenous estrogen with regard to risk of endometrial recurrence,
      it is noteworthy that the absolute recurrence rate (2.1%) and the incidence of
      new malignancy were low.

PMID- 16446333
TI  - Combined-modality therapy versus radiotherapy alone for treatment of early-stage
      Hodgkin's disease: cure balanced against complications.
AB  - PURPOSE: The treatment of early-stage Hodgkin's disease (HD) has evolved from
      radiotherapy alone (RT) to combined-modality therapy (CMT) because of concerns
      about late adverse effects from high-dose subtotal nodal irradiation (STNI).
      However, there is little information regarding the long-term results of CMT
      programs that substantially reduce the dose and extent of radiation. In addition,
      lowering the total radiation dose may reduce the complication rate without
      compromising cure. This retrospective study compares the long-term results of
      STNI with CMT using modestly reduced RT dose in the treatment of early-stage HD.
      PATIENTS AND METHODS: Between 1982 and 2002, 111 patients with stage IA and IIA
      HD were treated definitively with RT (mean dose, 37.9 Gy); 70 patients were
      treated with CMT with low-dose involved-field radiotherapy (LDIFRT; mean dose,
      25.5 Gy). Median follow-up was 11.7 years for RT patients and 8.1 years for the
      CMT group. RESULTS: There was a trend toward improved 20-year overall survival
      with CMT (83% v 70%; P = .405). No second cancers were observed in the CMT group;
      in the RT group the actuarial frequency of a second cancer was 16% at 20 years.
      There was no difference in the frequency of cardiac complications (9% v 6%, RT v
      CMT). CONCLUSION: In this retrospective review, CMT with LDIFRT was effective in
      curing early-stage HD and was not associated with an increase in second
      malignancies. For RT alone, a moderate dose seemed to reduce cardiac
      complications but did not lessen second malignancies compared with higher doses
      used historically.

PMID- 16446334
TI  - Phase II study of neoadjuvant chemotherapy and radiation therapy in the
      management of high-risk, high-grade, soft tissue sarcomas of the extremities and
      body wall: Radiation Therapy Oncology Group Trial 9514.
AB  - PURPOSE: On the basis of a positive reported single-institution pilot study, the
      Radiation Therapy Oncology Group initiated phase II trial 9514 to evaluate its
      neoadjuvant regimen in a multi-institutional Intergroup setting. PATIENTS AND
      METHODS: Eligibility included a high-grade soft tissue sarcoma > or = 8 cm in
      diameter of the extremities and body wall. Patients received three cycles of
      neoadjuvant chemotherapy (CT; modified mesna, doxorubicin, ifosfamide, and
      dacarbazine [MAID]), interdigitated preoperative radiation therapy (RT; 44 Gy
      administered in split courses), and three cycles of postoperative CT (modified
      MAID). RESULTS: Sixty-six patients were enrolled, of whom 64 were analyzed.
      Seventy-nine percent of patients completed their preoperative CT and 59%
      completed all planned CT. Three patients (5%) experienced fatal grade 5
      toxicities (myelodysplasias, two patients; infection, one patient). Another 53
      patients (83%) experienced grade 4 toxicities; 78% experienced grade 4
      hematologic toxicity and 19% experienced grade 4 nonhematologic toxicity. Sixty
      one patients underwent surgery. Fifty-eight of these were R0 resections, of which
      five were amputations. There were three R1 resections. The estimated 3-year rate
      for local-regional failure is 17.6% if amputation is considered a failure and
      10.1% if not. Estimated 3-year rates for disease-free, distant-disease-free, and
      overall survival are 56.6%, 64.5%, and 75.1%, respectively. CONCLUSION: This
      combined-modality treatment can be delivered successfully in a multi
      institutional setting. Efficacy results are consistent with previous single
      institution results.

PMID- 16446332
TI  - [18F]fluorodeoxyglucose positron emission tomography is more sensitive than
      skeletal scintigraphy for detecting bone metastasis in endemic nasopharyngeal
      carcinoma at initial staging.
AB  - PURPOSE: Bone metastasis occurs frequently in patients with endemic
      nasopharyngeal carcinoma (NPC). The main objective of this study is to evaluate
      positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose
      ([18F]FDG) and conventional skeletal scintigraphy (SS) for detecting bone
      metastasis at initial staging. Auxiliary objectives are to identify risk factors
      for bone metastasis and features associated with poor survival in patients with
      bone metastasis. PATIENTS AND METHODS: Patients with endemic NPC before
      initiation of treatment were enrolled. PET and SS were performed at initial
      staging and compared using McNemar's paired-sample test. Bone metastasis was
      considered to be present if there was any reliable evidence identified within 1
      year after primary diagnosis. Multiple logistic regression and Cox's proportional
      hazards models were used for auxiliary objectives. RESULTS: Thirty (15%) of 202
      eligible patients were found to have bone metastasis. [18F]FDG PET was found to
      be more sensitive than SS in the patient-based analysis (P = .006) and in the
      region-based analysis at the spine (P = .001). Advanced N stage was the only
      significant risk factor (P < .0001), and the coexistence of hepatic metastasis
      was a prognosticator of poor survival (P = .017). The survival was not
      significantly better for patients with bone metastasis undetected at primary
      staging than for those with initially detectable bone metastasis (P = .620).
      CONCLUSION: [18F]FDG PET is more sensitive than SS for detecting bone metastasis
      in endemic NPC at initial staging, whereas SS can be considered as supplementary
      in this setting.

PMID- 16446335
TI  - Impacting quality of life for patients with advanced cancer with a structured
      multidisciplinary intervention: a randomized controlled trial.
AB  - PURPOSE: The primary goal of this study was to evaluate the feasibility and
      effectiveness of a structured, multidisciplinary intervention targeted to
      maintain the overall quality of life (QOL), which is more comprehensive than
      psychosocial distress, of patients undergoing radiation therapy for advanced
      stage cancer. PATIENTS AND METHODS: Radiation therapy patients with advanced
      cancer and an estimated 5-year survival rate of 0% to 50% were randomly assigned
      to either an eight-session structured multidisciplinary intervention arm or a
      standard care arm. The eight 90-minute sessions addressed the five domains of QOL
      including cognitive, physical, emotional, spiritual, and social functioning. The
      primary end point of maintaining overall QOL was assessed by a single-item linear
      analog scale (Linear Analog Scale of Assessment or modified Spitzer Uniscale).
      QOL was assessed at baseline, week 4 (end of multidisciplinary intervention),
      week 8, and week 27. RESULTS: Of the 103 participants, overall QOL at week 4 was
      maintained by the patients in the intervention (n = 49), whereas QOL at week 4
      significantly decreased for patients in the control group (n = 54). This change
      reflected a 3-point increase from baseline in the intervention group and a 9
      point decrease from baseline in the control group (P = .009). Intervention
      participants maintained their QOL, and controls gradually returned to baseline by
      the end of the 6-month follow-up period. CONCLUSION: Although intervention
      participants maintained and actually improved their QOL during radiation therapy,
      control participants experienced a significant decrease in their QOL. Thus, a
      structured multidisciplinary intervention can help maintain or even improve QOL
      in patients with advanced cancer who are undergoing cancer treatment.

PMID- 16446337
TI  - Increased toxicity with gefitinib, capecitabine, and radiation therapy in
      pancreatic and rectal cancer: phase I trial results.
AB  - PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been
      associated with aggressive tumor phenotypes, chemotherapy, and radiation
      resistance, as well as poor survival in preclinical and clinical models. The EGFR
      inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in
      preclinical models, including pancreatic and colorectal cancer. We initiated two
      phase I trials assessing the combination of gefitinib, capecitabine, and
      radiation in patients with localized pancreatic and rectal cancer. PATIENTS AND
      METHODS: Patients with pathologically confirmed adenocarcinoma of the pancreas
      and rectum were eligible. Pretreatment staging included computed tomography,
      endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of
      external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and
      gefitinib were administered throughout the radiation course. Following
      completion, patients were restaged and considered for resection. Primary end
      points included determination of dose-limiting toxicity (DLT) and a phase II
      dose; secondary end points included determination of non-DLTs and preliminary
      radiographic and pathologic response rates. RESULTS: Ten patients were entered in
      the pancreatic study and six in the rectal study. DLT was seen in six of 10
      patients in the pancreatic study and two of six patients in the rectal study. The
      primary DLT in both studies was diarrhea. Two patients developed arterial
      thrombi. CONCLUSION: The combination of gefitinib, capecitabine, and radiation in
      pancreatic and rectal cancer patients resulted in significant toxicity. A
      recommended phase II dose was not determined in either of our studies. Further
      investigation with this combination should be approached with caution.

PMID- 16446336
TI  - Randomized phase II study of neoadjuvant combined-modality chemoradiation for
      distal rectal cancer: Radiation Therapy Oncology Group Trial 0012.
AB  - PURPOSE: To evaluate the rate of pathologic complete response and toxicity of
      neoadjuvant chemoradiation for advanced T3/T4 distal rectal cancers in a
      randomized phase II study PATIENTS AND METHODS: Patients with clinical T3/T4
      distal rectal cancers were randomly assigned in a phase II study to receive
      combined neoadjuvant chemoradiotherapy followed by surgical resection. Patients
      were randomly assigned to receive continuous venous infusion (CVI) fluorouracil
      (FU) 225 mg/m2 per day, 7 days per week, plus pelvic hyperfractionated radiation
      55.2 to 60 Gy at 1.2 Gy bid (arm 1) or CVI FU 225 mg/m2 per day Monday to Friday,
      120 hours per week plus irinotecan 50 mg/m2 once weekly for 4 weeks plus pelvic
      radiation therapy 50.4 to 54 Gy at 1.8 Gy per day (arm 2). Surgery was performed
      4 to 10 weeks after completion of neoadjuvant therapy. The primary end point of
      this study was pathologic complete response (pCR). Secondary end points included
      acute and late normal tissue morbidity. RESULTS: A total of 106 patients were
      entered onto the study, with 103 assessable for response. The overall
      resectability rate was 93%. The median time to surgery was 7 weeks. Tumor
      downstaging was observed in 78% of patients in both arms. The pCR rate for all
      assessable patients was 26% in each arm. For patients who had surgery, the pCR
      rate was also the same (28%) in both arms. Acute and late toxicity was also
      similar. Grade 3 and 4 acute hematologic and nonhematologic toxicity occurred in
      13% and 38% in arm 1 and 12% and 45% in arm 2, respectively. CONCLUSION: Although
      the overall complete response rate and toxicity seems similar in both arms, this
      is the first multi-institutional study to establish a relatively high (28%) pCR
      rate after neoadjuvant therapy.

PMID- 16446339
TI  - Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation
      and total mesorectal excision in magnetic resonance imaging-defined poor-risk
      rectal cancer.
AB  - PURPOSE: To evaluate neoadjuvant capecitabine/oxaliplatin before
      chemoradiotherapy (CRT) and total mesorectal excision (TME) in newly diagnosed
      patients with magnetic resonance imaging (MRI) -defined poor-risk rectal cancer.
      PATIENTS AND METHODS: MRI criteria for poor-risk rectal cancer were tumors within
      1 mm of mesorectal fascia (ie, circumferential resection margin threatened), T3
      tumors at or below levators, tumors extending > or = 5 mm into perirectal fat, T4
      tumors, and T1-4N2 tumors. Patients received 12 weeks of neoadjuvant
      capecitabine/oxaliplatin followed by concomitant capecitabine and radiotherapy.
      TME was planned 6 weeks after CRT. Postoperatively, patients received another 12
      weeks of capecitabine. RESULTS: Between November 2001 and August 2004, 77
      eligible patients were recruited. After neoadjuvant capecitabine/oxaliplatin, the
      radiologic response rate was 88%. In addition, 86% of patients had symptomatic
      responses in a median of 32 days (ie, just over one cycle of
      capecitabine/oxaliplatin). After CRT, the tumor response rate was increased to
      97%. Three patients remained inoperable. Sixty-seven patients proceeded to TME,
      and all but one patient had R0 resection. Pathologic complete response was
      observed in 16 patients (24%; 95% CI, 14% to 36%), and in an additional 32
      patients (48%), only microscopic tumor foci were found on surgical specimens.
      Four deaths occurred during neoadjuvant capecitabine/oxaliplatin therapy as a
      result of pulmonary embolism, ischemic heart disease, sudden death with history
      of chest pain, and neutropenic colitis. CONCLUSION: Capecitabine/oxaliplatin
      before synchronous CRT and TME results in substantial tumor regression, rapid
      symptomatic response, and achievement of R0 resection.

PMID- 16446340
TI  - Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone
      mineral density in premenopausal patients depending on menstrual status.
AB  - PURPOSE: Adjuvant chemotherapy followed by tamoxifen is a standard treatment
      option for women with intermediate or high-risk hormone receptor-positive breast
      cancer. Premenopausal women treated with chemotherapy often develop early
      menopause and thus, enter a period of accelerated bone loss. We conducted a
      prospective study of the effect of sequential adjuvant therapy with chemotherapy
      followed by tamoxifen on bone mineral density (BMD) in premenopausal patients.
      PATIENTS AND METHODS: One hundred eleven premenopausal women with early breast
      cancer were treated with adjuvant chemotherapy. Patients with hormone receptor
      positive tumors went on to tamoxifen 6 months after the beginning of the
      chemotherapy (tamoxifen group), while those with hormone receptor-negative tumors
      received no further therapy (control group). The effect of tamoxifen and
      menstrual status on BMD was studied. RESULTS: Tamoxifen treatment and menopausal
      status correlated significantly with the changes in lumbar spine BMD (P < .0001).
      A significant bone loss was noted in those tamoxifen-treated patients who
      continued to menstruate after chemotherapy. At 3 years of follow-up, menstruating
      patients on tamoxifen had lost -4.6% of their baseline BMD values, while a modest
      gain of +0.6% was noted in the control group. In contrast, bone loss was reduced
      among tamoxifen-treated women as compared with controls in patients who developed
      chemotherapy-induced early menopause. In amenorrheic patients, the lumbar spine
      BMD values decreased -6.8% in tamoxifen users and -9.5% in the controls,
      respectively. CONCLUSION: We conclude that tamoxifen usage was associated with
      bone loss in patients who continued to menstruate after adjuvant chemotherapy. On
      the contrary, tamoxifen decreased bone loss in those women who developed
      chemotherapy-induced amenorrhea.

PMID- 16446338
TI  - Multicenter phase II trial of S-1 plus cisplatin in patients with untreated
      advanced gastric or gastroesophageal junction adenocarcinoma.
AB  - PURPOSE: S-1 plus cisplatin is considered highly active in Japanese gastric
      cancer patients. We conducted a phase II multi-institutional trial, in the West,
      in patients with untreated advanced gastric or gastroesophageal junction
      adenocarcinoma to evaluate activity and safety of this combination. METHODS:
      Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at
      25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients
      with histologic proof of gastric or gastroesophageal junction adenocarcinoma with
      a Karnofsky performance status (KPS) of > or = 70% and near-normal organ function
      were eligible. All patients provided a written informed consent. To observe a 45%
      confirmed overall response rate (ORR), 41 assessable patients were needed.
      RESULTS: All 47 patients were assessed for safety and survival, and 41 patients
      were assessed for ORR. The median age was 56 years and median KPS was 80%. The
      median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI,
      35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71%
      of patients were alive, with a median survival time of 10.9 months. Frequent
      grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting
      (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile
      neutropenia (2%) were uncommon. There was one (2%) treatment-related death.
      CONCLUSION: S-1 plus cisplatin is active against gastric cancer and has a
      favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus
      fluorouracil plus cisplatin currently is accruing patients.

PMID- 16446341
TI  - Adding gemcitabine to paclitaxel/carboplatin combination increases survival in
      advanced non-small-cell lung cancer: results of a phase II-III study.
AB  - PURPOSE: Paclitaxel/carboplatin (PC) is one of the reference combinations in the
      treatment of non-small-cell lung cancer (NSCLC). No triplet novel agent
      combination has until now shown superiority over a two-drug combination for
      advanced NSCLC. We therefore conducted a clinical trial to test if
      paclitaxel/carboplatin/gemcitabine (PCG) increases overall survival (OS) and
      response rate (RR) over PC. METHODS: Stage IIIB patients not suitable for radical
      radiation treatment and stage IV chemotherapy-naive patients with measurable
      disease and performance status of 0 to 2 were randomly assigned to PC arm
      (paclitaxel 200 mg/m2 and carboplatin area under the concentration-time curve 6
      day 1/q21 days) or the PCG arm (paclitaxel 200 mg/m(2) and carboplatin area under
      the concentration-time curve 6 day 1, and gemcitabine 1,000 mg/m2 days 1 and 8
      every 21 days). RESULTS: A total of 324 patients were randomly assigned to the
      two arms. The RR for PC arm and PCG arm were 20.2% and 43.6% [corrected] (P <
      .0001). The median time to the progression was 5.1 months in the PC group and 7.6
      months in the PCG group (P = .012; hazard ratio [HR] 1.34; 95% CI: 1.06 to 1.72).
      Median OS was 8.3 months and 10.8 months (P = .032; HR 1.309; 95% CI: 1.03 to
      1.67) in favor of the PCG arm. One-year survival was 34% (PC arm) and 45% (PCG
      arm; P = .032). Only hematologic toxicity (neutropenia, thrombocytopenia, and
      anemia) was significantly increased in the PCG arm and the experimental arm
      required more platelet and red blood cell transfusions, and more granulocyte
      colony-stimulating factor usage. No toxic/early deaths were observed. CONCLUSION:
      The PCG regimen offers a significant survival advantage over PC in advanced
      NSCLC, making PCG a treatment option for advanced NSCLC patients.

PMID- 16446344
TI  - Sharing BRCA1/2 test results with first-degree relatives: factors predicting who
      women tell.
AB  - PURPOSE: Patient communication with relatives about cancer genetic test results
      is the primary means for alerting those who may benefit from identification of
      hereditary risk. This study identifies factors predicting patterns of disclosure
      of BRCA1/2 test results to first-degree relatives (FDRs) among women tested in a
      clinical protocol. PATIENTS AND METHODS: A total of 273 women completed a family
      communication measure 4 months after BRCA1/2 result disclosure. chi2 analyses and
      logistic regression models identified factors predicting sharing of the test
      result. RESULTS: Most FDRs were informed of the participant's test result by 4
      months; female relatives were more likely to be informed than males. Tested women
      conveyed inconclusive results (variant or negative without known familial
      mutation) less frequently to their sisters than conclusive (positive/true
      negative) results (P = .03). Twenty-three percent of participants did not inform
      their father. Informing brothers was more likely when BRCA1/2 was inherited
      through paternal lineage (P = .04), but 29% of brothers were not informed. Women
      older than age 40 were less likely to share their result with their parents (P =
      .03) than were women < or = 40. Children's ages influenced communication to
      offspring; most children were told. CONCLUSION: Demographic, health-, and test
      related factors predicted genetic test result communication to FDRs. Additional
      research investigating the full spectrum of discussion within families and
      motives for incomplete sharing of genetic test results with relatives may suggest
      strategies for providers and targeted educational interventions for patients to
      enhance family communication.

PMID- 16446343
TI  - Prognostic value of International Neuroblastoma Pathology Classification in
      localized resectable peripheral neuroblastic tumors: a histopathologic study of
      localized neuroblastoma European Study Group 94.01 Trial and Protocol.
AB  - PURPOSE: To assess the prognostic value of clinical, biologic, and morphologic
      data in peripheral neuroblastic tumors, International Neuroblastoma Staging
      System (INSS) stages 2A and 2B MYCN nonamplified, a multinational protocol
      entitled Localized Neuroblastoma European Study Group trial 94.01, with a trial
      of surgery as the only treatment, was initiated in 1995. We present the
      prognostic value of the revised International Neuroblastoma Pathology
      Classification (INPC) applied to the patients included in this protocol until its
      closure in 1999. MATERIALS AND METHODS: A total of 120 neuroblastic tumors from
      trial patients were reviewed by the European International Society of Pediatric
      Oncology neuroblastoma pathology panel and assigned to a favorable or unfavorable
      prognostic category according to the INPC guidelines. Overall survival and
      relapse-free survival (RFS) were estimated by the Kaplan-Meier method and
      compared by the log-rank test. RESULTS: A total of 115 of 120 patients were
      assessable and were assigned to the favorable (90 patients; 78.3%) or unfavorable
      (25 patients; 21.7%) category. The 60-month survival rate was 97.7% in favorable
      patients compared with 73.8% in unfavorable patients (P = .0002). RFS analysis
      showed a 60-month relapse rate of 13.4% and 32% in favorable and unfavorable
      patients (P < .025), respectively. Statistical analysis demonstrated a
      significant association of unfavorable INPC category and high lactate
      dehydrogenase level (P < .045). CONCLUSION: This European study shows for the
      first time that the INPC prognostic categorization has a significant impact on
      outcome prediction in INSS stage 2 localized peripheral neuroblastic tumors.

PMID- 16446342
TI  - Randomized phase II trial comparing nitroglycerin plus vinorelbine and cisplatin
      with vinorelbine and cisplatin alone in previously untreated stage IIIB/IV non
      small-cell lung cancer.
AB  - PURPOSE: To investigate the efficacy and safety of nitroglycerin plus vinorelbine
      and cisplatin in patients with previously untreated stage IIIB/IV non-small-cell
      lung cancer (NSCLC) as the experimental arm for the next phase III trial.
      PATIENTS AND METHODS: One hundred twenty patients with stage IIIB/IV NSCLC were
      randomly assigned to vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2
      on day 1, with transdermally applied nitroglycerin (25 mg/patient daily for 5
      days; arm A) or with placebo patch (arm B) every 3 weeks for a maximum of four
      cycles in a double-blind and controlled trial. Primary efficacy end points were
      the best confirmed response rate and time to disease progression (TTP). RESULTS:
      The response rate in arm A (72%; 43 of 60 patients) was significantly higher than
      that for patients in arm B (42%; 25 of 60 patients; P < .001). Median TTP in arm
      A was longer than that in arm B (327 v 185 days). No severe adverse effect was
      recognized for either arm. The rate of grade 1 to 2 headache in arm A (30%; 18 of
      60 patients) was significantly higher than that in arm B (2%; one of 60 patients;
      P < .001, chi(2) test). CONCLUSION: Use of nitroglycerin combined with
      vinorelbine and cisplatin may improve overall response and TTP in patients with
      stage IIIB/IV NSCLC. The arm A regimen is being evaluated in a large phase III
      trial.

PMID- 16446345
TI  - Optimal selection of individuals for BRCA mutation testing: a comparison of
      available methods.
AB  - PURPOSE: Several methods have been described that estimate the likelihood that a
      family history of cancer is a result of a mutation in the BRCA1 or BRCA2 genes.
      We examined the performance of six different methods with the aim of identifying
      an optimal strategy for selecting individuals for mutation testing in clinical
      practice. PATIENTS AND METHODS: Two hundred fifty-seven families who had
      completed BRCA1 and BRCA2 mutation screening were assessed by six models
      representing the major methodologies used to assess the likelihood of a
      pathogenic mutation. The performance of each method as a selection criterion was
      compared with the result of mutation testing to produce sensitivity, specificity,
      and receiver operating curve data. The impact of incorporating breast cancer
      pathology data in the assessment was also analyzed. RESULTS: The highest accuracy
      was achieved by the Bayesian probabilistic model (BRCAPRO). The formal
      probabilistic methods were significantly more accurate than clinical scoring
      methods. The methods were further improved by the incorporation of information on
      breast cancer pathology (tumor grade and estrogen receptor/progesterone receptor
      status). The resulting combined probability figure was highly accurate when
      selecting individuals for BRCA1 testing. Some BRCA2 mutation carriers were missed
      by all of the models examined. CONCLUSION: Formal probabilistic models provide
      significantly greater accuracy in the selection of families for gene testing than
      the use of clinical criteria or scoring methods. The accuracy is further enhanced
      by incorporating information on the pathology of breast cancers occurring in the
      families.

PMID- 16446346
TI  - Discussing bad news in the outpatient oncology clinic: rethinking current
      communication guidelines.

PMID- 16446347
TI  - Patient consent in the era of de-identified research databases.

PMID- 16446348
TI  - Molecular forecasting of breast cancer: time to move forward with clinical
      testing.

PMID- 16446349
TI  - The association between cognitive ability measured at ages 18-20 and mortality
      during 30 years of follow-up--a prospective observational study among Swedish
      males born 1949-51.
AB  - OBJECTIVES: An association between childhood cognitive ability measured with IQ
      tests and mortality has been reported recently. It is not clear from those
      studies if the relative risk is increased only among those in the lower end of
      the IQ score scale or if there is graded increase in mortality from the lowest to
      the highest. This study aims to investigate the association between cognitive
      ability measured at age 18-20 and mortality during a 30 year period of follow-up.
      METHODS: Data on cognitive ability was collected from 49,323 men, born in 1949
      51, who were conscripted for compulsory military training in 1969/70. Data on
      mortality were obtained from the Causes of Death register 1971-2000. RESULTS:
      Cognitive ability was a strong predictor of all-cause mortality, cardiovascular
      disease (CVD)-mortality, mortality from violent causes, and alcohol-related
      mortality. A striking finding was a pronounced gradient in mortality risk across
      all IQ score groups. Adjustment for adult socioeconomic position attenuated the
      increased risk somewhat [for all-cause mortality: crude hazard ratio (HR) 1.16
      (1.13-1.19), adjusted HR 1.12 (1.09-1.15)]. CONCLUSION: IQ test score measured in
      late adolescence (only males) was a significant predictor of all-cause, as well
      as cause-specific (CVD and injuries), mortality during 30 years of follow-up. The
      risk increased from high to low IQ test score results for all outcomes.

PMID- 16446350
TI  - Non-communicable diseases in low-income and middle-income countries: a debate?

PMID- 16446351
TI  - Preventing chronic disease: a priority for global health.

PMID- 16446352
TI  - Bayesian perspectives for epidemiological research: I. Foundations and basic
      methods.
AB  - One misconception (of many) about Bayesian analyses is that prior distributions
      introduce assumptions that are more questionable than assumptions made by
      frequentist methods; yet the assumptions in priors can be more reasonable than
      the assumptions implicit in standard frequentist models. Another misconception is
      that Bayesian methods are computationally difficult and require special software.
      But perfectly adequate Bayesian analyses can be carried out with common software
      for frequentist analysis. Under a wide range of priors, the accuracy of these
      approximations is just as good as the frequentist accuracy of the software--and
      more than adequate for the inaccurate observational studies found in health and
      social sciences. An easy way to do Bayesian analyses is via inverse-variance
      (information) weighted averaging of the prior with the frequentist estimate. A
      more general method expresses the prior distributions in the form of prior data
      or 'data equivalents', which are then entered in the analysis as a new data
      stratum. That form reveals the strength of the prior judgements being introduced
      and may lead to tempering of those judgements. It is argued that a criterion for
      scientific acceptability of a prior distribution is that it be expressible as
      prior data, so that the strength of prior assumptions can be gauged by how much
      data they represent.

PMID- 16446354
TI  - Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death
      requires RIP1/TRAF2-mediated JNK1 activation.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation-induced necrosis has been
      implicated in several pathophysiological conditions. Although mitochondrial
      dysfunction and apoptosis-inducing factor translocation from the mitochondria to
      the nucleus have been suggested to play very important roles in PARP-1-mediated
      cell death, the signaling events downstream of PARP-1 activation in initiating
      mitochondria dysfunction are not clear. Here we used the DNA alkylating agent N
      methyl-N'-nitro-N-nitrosoguanidine, a potent PARP-1 activator, to study PARP-1
      activation-mediated cell death. We found, based on genetic knockouts and
      pharmacological inhibition, that c-Jun N-terminal kinase (JNK), especially JNK1,
      but not the other groups of mitogen-activated protein kinase, is required for
      PARP-1-induced mitochondrial dysfunction, apoptosis-inducing factor
      translocation, and subsequent cell death. We reveal that receptor-interacting
      protein 1 (RIP1) and tumor necrosis factor receptor-associated factor 2 (TRAF2),
      are upstream of JNK in PARP-1 hyperactivated cells, because PARP-1-induced JNK
      activation was attenuated in RIP1-/- and TRAF2-/- mouse embryonic fibroblast
      cells. Consistently, knockouts of RIP1 and TRAF2 caused a resistance to PARP-1
      induced cell death. Therefore, our study uncovers that RIP1, TRAF2, and JNK
      comprise a pathway to mediate the signaling from PARP-1 overactivation to
      mitochondrial dysfunction.

PMID- 16446353
TI  - Height at age 18 years is a strong predictor of attained education later in life:
      cohort study of over 950,000 Swedish men.
AB  - BACKGROUND: Adult body height has been related to socioeconomic position in cross
      sectional studies. Intelligence, shared family factors, and non-familial
      circumstances may contribute to associations between height and attained
      education, but their relative importance has been difficult to resolve. METHODS:
      A nation-wide record-linkage cohort study of over 950 000 Swedish men born 1950
      75 followed with respect to attained education for up to 27 years after
      measurement of height at age 18 (baseline). The association between height and
      attained education in later life was investigated by logistic regression
      modelling with adjustment for age, geography, parental socioeconomic position,
      and cognitive ability. Shared family factors were accounted for in analyses of
      full-brother-pairs using conditional logistic regression. RESULTS: The odds ratio
      (OR) for attaining higher education 7-27 years after baseline was 1.10 [95%
      confidence interval (95% CI) 1.09-1.10] in fully adjusted models per 5 cm
      increase in height. Men taller than 194 cm were two to three times more likely to
      obtain a higher education as compared with men shorter than 165 cm. The
      association remained within brother-pairs, OR 1.08 (95% CI 1.07-1.10), suggesting
      that non-familial factors contribute to the association between height and
      education attainment. A significant interaction (P < 0.0001) was found between
      year of birth, height, and attained education, showing slightly weaker
      associations among later birth cohorts. CONCLUSIONS: The strong positive
      association between height and educational achievement remaining after adjustment
      for year of birth, parental socioeconomic position, other shared family factors,
      and cognitive ability may reflect educational discrimination based on height
      although residual confounding cannot be ruled out.

PMID- 16446355
TI  - Regulation of G protein-coupled receptor trafficking by inefficient plasma
      membrane expression: molecular basis of an evolved strategy.
AB  - Despite the prevalence of G protein-coupled receptors as transducers of signals
      from hormones, neurotransmitters, odorants, and light, little is known about
      mechanisms that regulate their plasma membrane expression (PME), although
      misfolded receptors are recognized and retained by a cellular quality control
      system (QCS). Convergent evolution of the gonadotropin-releasing hormone (GnRH)
      receptor (GnRHR) progressively decreases inositol phosphate production in
      response to agonist, validated as a measure of PME of receptor. A pharmacological
      chaperone that optimizes folding also increases PME of human, but not of rat or
      mouse, GnRHR because a higher percentage of human GnRHRs are misfolded structures
      due to their failure to form an apparent sulfhydryl bridge, and they are retained
      by the QCS. Bridge formation is increased by deleting (primate-specific) Lys191.
      In rat or mouse GnRHR that lacks Lys191, the bridge is non-essential and receptor
      is efficiently routed to the plasma membrane. Addition of Lys191 alone to the rat
      sequence did not diminish PME, indicating that other changes are required for its
      effects. A strategy, based on identification of amino acids that both 1) co
      evolved with the Lys191 and 2) were thermodynamically unfavorable substitutions,
      identified motifs in multiple domains of the human receptor that control the
      destabilizing influence of Lys191 on a particular Cys bridge, resulting in
      diminished PME. The data show a novel and underappreciated means of
      posttranslational control of a G protein-coupled receptor by altering its
      interaction with the QCS and provide a biochemical explanation of the basis of
      disease-causing mutations of this receptor.

PMID- 16446356
TI  - The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity
      in mice.
AB  - The farnesoid X receptor (FXR) is a bile acid (BA)-activated nuclear receptor
      that plays a major role in the regulation of BA and lipid metabolism. Recently,
      several studies have suggested a potential role of FXR in the control of hepatic
      carbohydrate metabolism, but its contribution to the maintenance of peripheral
      glucose homeostasis remains to be established. FXR-deficient mice display
      decreased adipose tissue mass, lower serum leptin concentrations, and elevated
      plasma free fatty acid levels. Glucose and insulin tolerance tests revealed that
      FXR deficiency is associated with impaired glucose tolerance and insulin
      resistance. Moreover, whole-body glucose disposal during a hyperinsulinemic
      euglycemic clamp is decreased in FXR-deficient mice. In parallel, FXR deficiency
      alters distal insulin signaling, as reflected by decreased insulin-dependent Akt
      phosphorylation in both white adipose tissue and skeletal muscle. Whereas FXR is
      not expressed in skeletal muscle, it was detected at a low level in white adipose
      tissue in vivo and induced during adipocyte differentiation in vitro. Moreover,
      mouse embryonic fibroblasts derived from FXR-deficient mice displayed impaired
      adipocyte differentiation, identifying a direct role for FXR in adipocyte
      function. Treatment of differentiated 3T3-L1 adipocytes with the FXR-specific
      synthetic agonist GW4064 enhanced insulin signaling and insulin-stimulated
      glucose uptake. Finally, treatment with GW4064 improved insulin resistance in
      genetically obese ob/ob mice in vivo. Although the underlying molecular
      mechanisms remain to be unraveled, these results clearly identify a novel role of
      FXR in the regulation of peripheral insulin sensitivity and adipocyte function.
      This unexpected function of FXR opens new perspectives for the treatment of type
      2 diabetes.

PMID- 16446357
TI  - TAK1 is a component of the Epstein-Barr virus LMP1 complex and is essential for
      activation of JNK but not of NF-kappaB.
AB  - Epstein-Barr virus latent membrane protein 1 (LMP1) activates NF-kappaB and c-Jun
      N-terminal kinase (JNK), which is essential for LMP1 oncogenic activity. Genetic
      analysis has revealed that tumor necrosis factor receptor-associated factor 6
      (TRAF6) is an indispensable intermediate of LMP1 signaling leading to activation
      of both NF-kappaB and JNK. However, the mechanism by which LMP1 engages TRAF6 for
      activation of NF-kappaB and JNK is not well understood. Here we demonstrate that
      TAK1 mitogen-activated protein kinase kinase kinase and TAK1-binding protein 2
      (TAB2), together with TRAF6, are recruited to LMP1 through its N-terminal
      transmembrane region. The C-terminal cytoplasmic region of LMP1 facilitates the
      assembly of this complex and enhances activation of JNK. In contrast, IkappaB
      kinase gamma is recruited through the C-terminal cytoplasmic region and this is
      essential for activation of NF-kappaB. Furthermore, we found that ablation of
      TAK1 resulted in the loss of LMP1-induced activation of JNK but not of NF-kappaB.
      These results suggest that an LMP1-associated complex containing TRAF6, TAB2, and
      TAK1 plays an essential role in the activation of JNK. However, TAK1 is not an
      exclusive intermediate for NF-kappaB activation in LMP1 signaling.

PMID- 16446358
TI  - The DNA binding activity of MutL is required for methyl-directed mismatch repair
      in Escherichia coli.
AB  - The DNA binding properties of the mismatch repair protein MutL and their
      importance in the repair process have been controversial for nearly two decades.
      We have addressed this issue using a point mutant of MutL (MutL-R266E). The
      biochemical and genetic data suggest that DNA binding by MutL is required for dam
      methylation-directed mismatch repair. We demonstrate that purified MutL-R266E
      retains wild-type biochemical properties that do not depend on DNA binding, such
      as basal ATP hydrolysis in the absence of DNA and the ability to interact with
      other mismatch repair proteins. However, purified MutL-R266E binds DNA poorly in
      vitro as compared with MutL, and consistent with this observation, its DNA
      dependent biochemical activities, like DNA-stimulated ATP hydrolysis and helicase
      II stimulation, are severely compromised. In addition, there is a modest effect
      on stimulation of MutH-catalyzed nicking. Finally, genetic assays show that MutL
      R266E has a strong mutator phenotype, demonstrating that the mutant is unable to
      function in dam methylation-directed mismatch repair in vivo.

PMID- 16446359
TI  - The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum
      associated degradation pathway to mediate down-regulation of major
      histocompatibility complex class I proteins.
AB  - Ubiquitin E3 ligases are important cellular components for endoplasmic reticulum
      (ER)-associated degradation due to their role in substrate-specific
      ubiquitination, which is required for retrotranslocation (dislocation) of most
      unwanted proteins from the ER to the cytosol for proteasome degradation. However,
      our understanding of the molecular mechanisms of how E3 ligases confer substrate
      specific recognition, and their role in substrate retrotranslocation is limited
      especially in mammalian cells. mK3 is a type III ER membrane protein encoded by
      murine gamma herpesvirus 68. As conferred by its N-terminal RING-CH domain, mK3
      has E3 ubiquitin ligase activity. In its role as an immune evasion protein, mK3
      specifically targets nascent major histocompatibility complex class I heavy
      chains (HC) for rapid degradation. The mechanism by which mK3 extracts HC from
      the ER membrane into the cytosol for proteasome-mediated degradation is unknown.
      Evidence is presented here that HC down-regulation by mK3 is dependent on the p97
      AAA-ATPase. By contrast, the kK5 protein of Kaposi's sarcoma-associated
      herpesvirus is p97-independent despite the fact that it is highly homologous to
      mK3. mK3 protein was also found in physical association with Derlin1, an ER
      protein recently implicated in the retrotranslocation of HC by immune evasion
      protein US11, but not US2, of human cytomegalovirus. The mechanistic implications
      of these findings are discussed.

PMID- 16446364
TI  - 20S proteasomes have the potential to keep substrates in store for continual
      degradation.
AB  - The 20S core of the proteasome, which together with the regulatory particle plays
      a major role in the degradation of proteins in eukaryotic cells, is traversed by
      an internal system of cavities, namely two antechambers and one central
      proteolytic chamber. Little is known about the mechanisms underlying substrate
      binding and translocation of polypeptide chains into the interior of 20S
      proteasomes. Specifically, the role of the antechambers is not fully understood,
      and the number of substrate molecules sequestered within the internal cavities at
      any one time is unknown. Here we have shown that by applying both electron
      microscopy and tandem mass spectrometry (MS) approaches to this multisubunit
      complex we obtain precise information regarding the stoichiometry and location of
      substrates within the three chambers. The dissociation pattern in tandem MS
      allows us to conclude that a maximum of three green fluorescent protein and four
      cytochrome c substrate molecules are bound within the cavities. Our results also
      show that >95% of the population of proteasome molecules contain the maximum
      number of partially folded substrates. Moreover, we deduce that one green
      fluorescent protein or two cytochrome c molecules must reside within the central
      proteolytic chamber while the remaining substrate molecules occupy, singly, both
      antechambers. The results imply therefore an additional role for 20S proteasomes
      in the storage of substrates prior to their degradation, specifically in cases
      where translocation rates are slower than proteolysis. More generally, the
      ability to locate relatively small protein ligands sequestered within the 28
      subunit core particle highlights the tremendous potential of tandem MS for
      deciphering substrate binding within large macromolecular assemblies.

PMID- 16446360
TI  - Identification of Mcm2 phosphorylation sites by S-phase-regulating kinases.
AB  - Minichromosome maintenance 2-7 proteins play a pivotal role in replication of the
      genome in eukaryotic organisms. Upon entry into S-phase several subunits of the
      MCM hexameric complex are phosphorylated. It is thought that phosphorylation
      activates the intrinsic MCM DNA helicase activity, thus allowing formation of
      active replication forks. Cdc7, Cdk2, and ataxia telangiectasia and Rad3-related
      kinases regulate S-phase entry and S-phase progression and are known to
      phosphorylate the Mcm2 subunit. In this work, by in vitro kinase reactions and
      mass spectrometry analysis of the products, we have mapped phosphorylation sites
      in the N terminus of Mcm2 by Cdc7, Cdk2, Cdk1, and CK2. We found that Cdc7
      phosphorylates Mcm2 in at least three different sites, one of which corresponds
      to a site also reported to be phosphorylated by ataxia telangiectasia and Rad3
      related. Three serine/proline sites were identified for Cdk2 and Cdk1, and a
      unique site was phosphorylated by CK2. We raised specific anti-phosphopeptide
      antibodies and found that all the sites identified in vitro are also
      phosphorylated in cells. Importantly, although all the Cdc7-dependent Mcm2
      phosphosites fluctuate during the cell cycle with kinetics similar to Cdc7 kinase
      activity and Cdc7 protein levels, phosphorylation of Mcm2 in the putative cyclin
      dependent kinase (Cdk) consensus sites is constant during the cell cycle.
      Furthermore, our analysis indicates that the majority of the Mcm2 isoforms
      phosphorylated by Cdc7 are not stably associated with chromatin. This study forms
      the basis for understanding how MCM functions are regulated by multiple kinases
      within the cell cycle and in response to external perturbations.

PMID- 16446361
TI  - Dual role for transactivator protein C in activation of mom promoter of
      bacteriophage Mu.
AB  - Transactivator C protein of bacteriophage Mu activates the mom gene of the phage
      by an unusual mechanism. DNA binding by C to its site results in unwinding of the
      neighboring sequences, realigning the out-of-phase promoter elements to
      facilitate RNA polymerase (RNAP) binding. High level stimulation of a C
      independent constitutive promoter mutant (where RNAP is already bound) by the
      transactivator suggested an additional mechanism of transcription activation at a
      step after RNAP recruitment. In this study, we have investigated the various
      steps of promoter-polymerase interactions during transcription initiation by
      using both the promoter mutant and a positive control (pc) mutant of C protein.
      The transactivator does not influence formation of the open complex or its
      stability after facilitating the RNAP binding. However, at a subsequent step, the
      protein exerts an important role, enhancing the promoter clearance by increasing
      the productive RNAP.promoter complex. The pc mutant of the transactivator C is
      compromised at this step, supporting the additional downstream role for C in mom
      transcription activation. We suggest that this unusual multistep activation of
      Pmom has evolved to ensure irreversibility of the switch during the late lytic
      cycle of the phage.

PMID- 16446363
TI  - Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core
      dependent nuclear delocalization of cyclin B1.
AB  - Some hepatitis C virus (HCV) proteins, including core protein, deregulate the
      cell cycle of infected cells, thereby playing an important role in the viral
      pathogenesis of HCC. Thus far, there are only few studies that have deeply
      investigated in depth the effects of the HCV core protein expression on the
      progression through the G1/S and G2/M phases of the cell cycle. To shed light on
      the molecular mechanisms by which the HCV core protein modulates cell
      proliferation, we have examined its effects on cell cycle in hepatocarcinoma
      cells. We show here that HCV core protein perturbs progression through both the
      G1/S and the G2/M phases, by modulating the expression and the activity of
      several cell cycle regulatory proteins. In particular, our data provided evidence
      that core-dependent deregulation of the G1/S phase and its related cyclin-CDK
      complexes depends upon the ERK1/2 pathway. On the other hand, the viral protein
      also increases the activity of the cyclin B1-CDK1 complex via the p38 MAPK and
      JNK pathways. Moreover, we show that HCV core protein promotes nuclear import of
      cyclin B1, which is affected by the inhibition of both the p38 and the RNA
      dependent protein kinase (PKR) activities. The important role of p38 MAPK in
      regulating G2/M phase transition has been previously documented. It is becoming
      clear that PKR has an important role in regulating both the G1/S and the G2/M
      phase, in which it induces M phase arrest. Based on our model, we now show, for
      the first time, that HCV core expression leads to deregulation of the mitotic
      checkpoint via a p38/PKR-dependent pathway.

PMID- 16446362
TI  - Cyclic GMP-dependent protein kinase Ialpha inhibits thrombin receptor-mediated
      calcium mobilization in vascular smooth muscle cells.
AB  - Vascular smooth muscle contractile state is regulated by intracellular calcium
      levels. Nitric oxide causes vascular relaxation by stimulating production of
      cyclic GMP, which activates type I cGMP-dependent protein kinase (PKGI) in
      vascular smooth muscle cells (VSMC), inhibiting agonist-induced intracellular
      Ca2+ mobilization ([Ca2+]i). The relative roles of the two PKGI isozymes,
      PKGIalpha and PKGIbeta, in cyclic GMP-mediated inhibition of [Ca2+]i in VSMCs are
      unclear. Here we have investigated the ability of PKGI isoforms to inhibit
      [Ca2+]i in response to VSMC activation. Stable Chinese hamster ovary cell lines
      expressing PKGIalpha or PKGIbeta were created, and the ability of PKGI isoforms
      to inhibit [Ca2+]i in response to thrombin receptor stimulation was examined. In
      Chinese hamster ovary cells stably expressing PKGIalpha or PKGIbeta, 8-Br-cGMP
      activation suppressed [Ca2+]i by thrombin receptor activation peptide (TRAP) by
      98 +/- 1 versus 42 +/- 5%, respectively (p <0.002). Immunoblotting studies of
      cultured human VSMC cells from multiple sites using PKGIalpha- and PKGIbeta
      specific antibodies showed PKGIalpha is the predominant VSMC PKGI isoform.
      [Ca2+]i following thrombin receptor stimulation was examined in the absence or
      presence of cyclic GMP in human coronary VSMC cells (Co403). 8-Br-cGMP
      significantly inhibited TRAP-induced [Ca2+]i in Co403, causing a 4-fold increase
      in the EC50 for [Ca2+]i. In the absence of 8-Br-cGMP, suppression of PKGIalpha
      levels by RNA interference (RNAi) led to a significantly greater TRAP-stimulated
      rise in [Ca2+]i as compared with control RNAi-treated Co403 cells. In the
      presence of 8-Br-cGMP, the suppression of PKGIalpha expression by RNAi led to the
      complete loss of cGMP-mediated inhibition of [Ca2+]i. Adenoviral overexpression
      of PKGIbeta in Co403 cells was unable to alter TRAP-stimulated Ca2+ mobilization
      either before or after suppression of PKGIalpha expression by RNAi. These results
      support that PKGIalpha is the principal cGMP-dependent protein kinase isoform
      mediating inhibition of VSMC activation by the nitric oxide/cyclic GMP pathway.

PMID- 16446365
TI  - Targeted knockdown of G protein subunits selectively prevents receptor-mediated
      modulation of effectors and reveals complex changes in non-targeted signaling
      proteins.
AB  - Heterotrimeric G protein signaling specificity has been attributed to select
      combinations of Galpha, beta, and gamma subunits, their interactions with other
      signaling proteins, and their localization in the cell. With few exceptions, the
      G protein subunit combinations that exist in vivo and the significance of these
      specific combinations are largely unknown. We have begun to approach these
      problems in HeLa cells by: 1) determining the concentrations of Galpha and Gbeta
      subunits; 2) examining receptor-dependent activities of two effector systems
      (adenylyl cyclase and phospholipase Cbeta); and 3) systematically silencing each
      of the Galpha and Gbeta subunits by using small interfering RNA while quantifying
      resultant changes in effector function and the concentrations of other relevant
      proteins in the network. HeLa cells express equimolar amounts of total Galpha and
      Gbeta subunits. The most prevalent Galpha proteins were one member of each Galpha
      subfamily (Galpha(s), Galpha(i3), Galpha(11), and Galpha(13)). We substantially
      abrogated expression of most of the Galpha and Gbeta proteins expressed in these
      cells, singly and some in combinations. As expected, agonist-dependent activation
      of adenylyl cyclase or phospholipase Cbeta was specifically eliminated following
      the silencing of Galpha(s) or Galpha(q/11), respectively. We also confirmed that
      Gbeta subunits are necessary for stable accumulation of Galpha proteins in vivo.
      Gbeta subunits demonstrated little isoform specificity for receptor-dependent
      modulation of effector activity. We observed compensatory changes in G protein
      accumulation following silencing of individual genes, as well as an apparent
      reciprocal relationship between the expression of certain Galpha(q) and Galpha(i)
      subfamily members. These findings provide a foundation for understanding the
      mechanisms that regulate the adaptability and remarkable resilience of G protein
      signaling networks.

PMID- 16446367
TI  - Structure and activation mechanism of the Drosophila initiator caspase Dronc.
AB  - Activation of an initiator caspase is essential to the execution of apoptosis.
      The molecular mechanisms by which initiator caspases are activated remain poorly
      understood. Here we demonstrate that the autocatalytic cleavage of Dronc, an
      important initiator caspase in Drosophila, results in a drastic enhancement of
      its catalytic activity in vitro. The autocleaved Dronc forms a homodimer, whereas
      the uncleaved Dronc zymogen exists exclusively as a monomer. Thus the
      autocatalytic cleavage in Dronc induces its stable dimerization, which presumably
      allows the two adjacent monomers to mutually stabilize their active sites,
      leading to activation. Crystal structure of a prodomain-deleted Dronc zymogen,
      determined at 2.5 A resolution, reveals an unproductive conformation at the
      active site, which is consistent with the observation that the zymogen remains
      catalytically inactive. This study revealed insights into mechanism of Dronc
      activation, and in conjunction with other observations, suggests diverse
      mechanisms for the activation of initiator caspases.

PMID- 16446366
TI  - Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation.
AB  - Wnt signaling plays pivotal roles in the regulation of embryogenesis and cancer
      development. Xenopus Dapper (Dpr) was identified as an interacting protein for
      Dishevelled (Dvl), a Wnt signaling mediator, and modulates Wnt signaling.
      However, it is largely unclear how Dpr regulates Wnt signaling. Here, we present
      evidence that human Dpr1, the ortholog of Xenopus Dpr, inhibits Wnt signaling. We
      have identified the regions responsible for the Dpr-Dvl interaction in both
      proteins and found that the interaction interface is formed between the DEP
      (Dishevelled, Egl-10, and pleckstrin) domain of Dvl and the central and the C
      terminal regions of Dpr1. The inhibitory function of human Dpr1 requires both its
      N and C terminus. Overexpression of the C-terminal region corresponding to the
      last 225 amino acids of Dpr1, in contrast to wild-type Dpr1, enhances Wnt
      signaling, suggesting a dominant negative function of this region. Furthermore,
      we have shown that Dpr1 induces Dvl degradation via a lysosome inhibitor
      sensitive and proteasome inhibitor-insensitive mechanism. Knockdown of Dpr1 by
      RNA interference up-regulates endogenous Dvl2 protein. Taken together, our data
      indicate that the inhibitory activity of Dpr on Wnt signaling is conserved from
      Xenopus to human and that Dpr1 antagonizes Wnt signaling by inducing Dvl
      degradation.

PMID- 16446368
TI  - Regions of the catalytic alpha subunit of Na,K-ATPase important for functional
      interactions with FXYD 2.
AB  - The gamma modulator (FXYD 2) is a member of the FXYD family of single
      transmembrane proteins that modulate the kinetic behavior of Na,K-ATPase. This
      study concerns the identification of regions in the alpha subunit that are
      important for its functional interaction with gamma. An important effect of gamma
      is to increase K+ antagonism of cytoplasmic Na+ activation apparent as an
      increase in KNa' at high [K+]. We show that although gamma associates with
      alpha1, alpha2, and alpha3 isoforms, it increases the KNa' of alpha1 and alpha3
      but not alpha2. Accordingly, chimeras of alpha1 and alpha2 were used to identify
      regions of alpha critical for the increased KNa'. As with alpha1 and alpha2, all
      chimeras associate with gamma. Kinetic analysis of alpha2front/alpha1back
      chimeras indicate that the C-terminal (Lys907-Tyr1018) region of alpha1, which
      includes transmembrane (TM)9 close to gamma, is important for the increase in
      KNa'. However, similar experiments with alpha1front/alpha2back chimeras indicate
      a modulatory role of the loop between TMs 7 and 8. Thus, as long as the alpha1
      L7/8 loop is present, replacement of TM9 of alpha1 with that of alpha2 does not
      abrogate the gamma effect on KNa'. In contrast, as long as TM9 is that of alpha1,
      replacement of L7/8 of alpha1 with that of alpha2 does not abolish the effect. It
      is suggested that structural association of the TM regions of alpha and FXYD 2 is
      not the sole determinant of this effect of FXYD on KNa' but is subject to long
      range modulation by the extramembranous L7/8 loop of alpha.

PMID- 16446369
TI  - GPX2, a direct target of p63, inhibits oxidative stress-induced apoptosis in a
      p53-dependent manner.
AB  - The p53 family consists of p53, p63, and p73, each of which has multiple isoforms
      due to transcription at two separate promoters and alternative splicing. Although
      p53 is a bona fide tumor suppressor, p63 appears to have a Janus-faced function
      as a tumor suppressor and an oncogene. To address the two opposing functions of
      p63, we analyzed its target genes. Here, we found that GPX2, which encodes a
      glutathione peroxidase, is up-regulated by p63 but not p53. Accordingly, a unique
      responsive element was found in the promoter of the GPX2 gene that can be
      activated and bound by p63 but not p53. We also found that upon overexpression,
      GPX2 alleviates the apoptotic response of MCF7 cells to oxidative stresses.
      Interestingly, the protective function of GPX2 is p53 dependent. Likewise, we
      showed that a deficiency in GPX2 renders MCF7 cells susceptible to oxidative
      stress-induced apoptosis. Given that the deltaN isoform of p63 is frequently
      overexpressed in tumor cells, the observations here provide an insight into the
      mechanism by which some isoforms of p63 serve as a pro-survival factor by up
      regulating GPX2 to reduce the p53-dependent oxidative stress-induced apoptotic
      response.

PMID- 16446375
TI  - OXA-type carbapenemases.
AB  - In recent years, the number of class D beta-lactamases with carbapenem
      hydrolysing properties has increased substantially. Based on amino acid sequence
      identities, these class D or OXA-type carbapenemases are divided into eight
      distantly related groups, and they are only remotely related to other class D
      beta-lactamases. A putative ancestor to one of the plasmid-encoded OXA-type
      carbapenemases has been found. OXA-type carbapenemases are not integrated into
      integrons as gene cassettes like many class D oxacillinases, but most of the OXA
      type carbapenemases are instead encoded by chromosomal genes. Some of these OXA
      type carbapenemases are widely dispersed in Pseudomonas aeruginosa and especially
      in Acinetobacter baumannii. Although most of the OXA-type carbapenemases show
      only weak carbapenemase activity, carbapenem resistance may result from a
      combined action an OXA-type carbapenemase and a secondary resistance mechanism
      such as porin deficiencies or overexpressed efflux pumps. This article reviews
      the phylogeny and the genetic environments of the encoding genes and kinetic
      properties of the OXA-type carbapenemases.

PMID- 16446373
TI  - Resistance to a polyquaternium-1 lens care solution and isoelectric points of
      Pseudomonas aeruginosa strains.
AB  - OBJECTIVES: The aim of this study was to correlate the cell surface
      hydrophobicity and charge of various strains of Pseudomonas aeruginosa with their
      resistance to a polyquaternium-1 lens care solution. METHODS: The 11 P.
      aeruginosa strains included were isolated from eyes, contact lenses, lens cases
      and lens care solutions. Cell surface hydrophobicities were determined from water
      contact angle measurements and surface charges were measured as a function of pH
      using particulate micro-electrophoresis. RESULTS: Strains resistant to
      polyquaternium-1 had an isoelectric point (IEP; pH where the bacterial zeta
      potential is zero) ranging from 4.0 to 5.5, whereas susceptible strains were more
      negatively charged than resistant strains and had an IEP between 1.3 and 1.9.
      Water contact angles ranged from hydrophilic (34 degrees) to hydrophobic (124
      degrees), without showing a relation with antimicrobial resistance. CONCLUSIONS:
      Results suggest that electrostatic repulsion between cationic molecules on the
      cell surface and quaternary ammonium compounds impedes the antimicrobial entering
      the cell.

PMID- 16446371
TI  - PS-341 (bortezomib) induces lysosomal cathepsin B release and a caspase-2
      dependent mitochondrial permeabilization and apoptosis in human pancreatic cancer
      cells.
AB  - PS-341 (bortezomib) is a potent and reversible proteosome inhibitor that
      functions to degrade intracellular polyubiquitinated proteins. PS-341 induces
      apoptosis and has shown broad antitumor activity with selectivity for transformed
      cells. We studied the effect of PS-341 on lysosomal and mitochondrial
      permeabilization, including the role of caspase-2 activation in apoptosis
      induction in the BxPC-3 human pancreatic carcinoma cell line. PS-341 induced a
      dose-dependent apoptosis in association with reactive oxygen species generation
      and cleavage of caspase-2 to its 33- and 14-kDa fragments. PS-341 disrupted
      lysosomes with redistribution of cathepsin B to the cytosol, as shown using
      fluorescence confocal microscopy, that was blocked by the free radical scavenger
      tiron but not by a caspase-2 inhibitor (benzyloxycarbonyl (Z)-VDVAD-fluoromethyl
      ketone (FMK)). PS-341-induced caspase-2 activation was attenuated by a selective
      pharmacological inhibitor of cathepsin B (R-3032), suggesting that cathepsin B
      release occurs upstream of caspase-2. PS-341-induced mitochondrial depolarization
      was attenuated by Z-VDVAD-FMK, tiron, and an inhibitor of the mitochondrial
      permeability transition pore (bongkrekic acid). Regulation of mitochondrial
      permeability by caspase-2 was confirmed using caspase-2 small interfering RNA. PS
      341-induced cytochrome c release and phosphatidylserine externalization were
      attenuated by Z-VDVAD-FMK and partially by R-3032. PS-341 activated the BH3-only
      proteins Bik and Bim and down-regulated Bcl-2 and Bcl-xL mRNA and protein
      expression. Taken together, PS-341 induces lysosomal cathepsin B redistribution
      upstream of caspase-2. Caspase-2 activation regulates PS-341-induced
      mitochondrial depolarization and apoptosis, suggesting that caspase-2 can serve
      as a link between lysosomal and mitochondrial permeabilization.

PMID- 16446372
TI  - Aryl hydrocarbon receptor modulation of tumor necrosis factor-alpha-induced
      apoptosis and lysosomal disruption in a hepatoma model that is caspase-8
      independent.
AB  - Recent studies suggest that the aryl hydrocarbon receptor (AhR) modulates
      susceptibilities to some pro-apoptotic agents. AhR-containing murine hepatoma
      1c1c7 cultures underwent apoptosis following exposure to tumor necrosis factor
      alpha (TNFalpha) + cycloheximide (CHX). In contrast, Tao cells, an AhR-deficient
      variant of the 1c1c7 line, were refractory to this treatment. AhR sense/antisense
      transfection studies demonstrated that AhR contents influenced susceptibility to
      the pro-apoptotic effects of TNFalpha + CHX. 1c1c7 cells and all variants
      expressed comparable amounts of TNF receptor-1 and TRADD. However, no cell line
      expressed FADD, and consequently pro-caspase-8 was not activated. AhR content did
      not influence JNK and NF-kappaB activation. However, Bid and pro-caspase-9, -3,
      and -12 processing occurred only in AhR-containing cells. Analyses of cathepsin B
      and D activities in digitonin-permeabilized cultures and the monitoring of
      cathepsin B/D co-localization with Lamp-1 indicated that TNFalpha + CHX disrupted
      late endosomes/lysosomes in only AhR-containing cells. Stabilization of acidic
      organelles with 3-O-methylsphingomyelin inhibited TNFalpha + CHX-induced
      apoptosis. The cathepsin D inhibitor pepstatin A suppressed in vitro cleavage of
      Bid by 1c1c7 lysosomal extracts. It also delayed the induction of apoptosis and
      partially prevented Bid cleavage and the activation of pro-caspases-3/7 in
      cultures treated with TNFalpha + CHX. Similar suppressive effects occurred in
      cultures transfected with murine Bid antisense oligonucleotides. These studies
      showed that in cells where pro-caspase-8 is not activated, TNFalpha + CHX can
      initiate apoptosis through lysosomal disruption. Released proteases such as
      cathepsin D trigger the apoptotic program by activating Bid. Furthermore, in the
      absence of exogenous ligand, the AhR modulates lysosomal disruption/permeability.

PMID- 16446374
TI  - Comparative study on the efficacy of AmBisome and Fungizone in a mouse model of
      pulmonary aspergillosis.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy and tissue
      concentration of AmBisome and Fungizone in murine pulmonary aspergillosis, and to
      investigate the localization of AmBisome at the infection site. METHODS: Mice
      were infected intratracheally with Aspergillus fumigatus. A single dose of each
      of the antifungals was administered intravenously 4 h after infection. The
      efficacy of the antifungal treatment was assessed by the pulmonary fungal burden
      at 20 h post-treatment and the survival time over 1 month. The pulmonary
      amphotericin B (AMB) concentration was measured until 48 h after administration.
      The distribution of AmBisome in the lung was evaluated using rhodamine-labelled
      AmBisome and an anti-AMB antibody. RESULTS: AmBisome at a dose of > or =1 mg/kg
      significantly prolonged the survival time of infected mice compared with the
      control group. At the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater
      efficacy than 1 mg/kg Fungizone in terms of increasing survival and reducing the
      fungal burden. The pulmonary AMB concentration of 10 mg/kg AmBisome was higher
      than that of 1 mg/kg Fungizone. Tissue distribution analysis showed that AmBisome
      was localized at the infection site in the lung, and this might explain the
      potent in vivo efficacy in this infection model. CONCLUSIONS: AmBisome is
      localized at the infection site in the lung and consequently may fully exhibit
      its in vivo activity. The efficacy of AmBisome is superior to that of Fungizone
      against pulmonary aspergillosis.

PMID- 16446370
TI  - DNA damage-induced expression of p53 suppresses mitotic checkpoint kinase hMps1:
      the lack of this suppression in p53MUT cells contributes to apoptosis.
AB  - DNA damage induced by the topoisomerase I inhibitor irinotecan (CPT-11) triggers
      in p53(WT) colorectal carcinoma cells a long term cell cycle arrest and in p53MUT
      cells a transient arrest followed by apoptosis (Magrini, R., Bhonde, M. R.,
      Hanski, M. L., Notter, M., Scherubl, H., Boland, C. R., Zeitz, M., and Hanski, C.
      (2002) Int. J. Cancer 101, 23-31; Bhonde, M. R., Hanski, M. L., Notter, M.,
      Gillissen, B. F., Daniel, P. T., Zeitz, M., and Hanski, C. (2006) Oncogene 25,
      165-175). The mechanism of the p53-independent apoptosis still remains largely
      unclear. Here we used five p53WT and five p53MUT established colon carcinoma cell
      lines to identify gene expression alterations associated with apoptosis in p53MUT
      cells after treatment with SN-38, the irinotecan metabolite. After treatment, 16
      mitosis-related genes were found to be expressed at least 2-fold stronger in the
      apoptosis-executing p53MUT cells than in the cell cycle-arrested p53WT cells by
      oligonucleotide microarray analysis. One of the genes whose strong post-treatment
      expression was associated with apoptosis was the mitotic checkpoint kinase hMps1
      (human ortholog of the yeast monopolar spindle 1 kinase). hMps1 mRNA and protein
      expression were suppressed by the treatment-induced and by the exogenous
      adenovirus-coded p53 protein. The direct suppression of hMps1 on RNA level or
      inhibition of its activity by a dominant-negative hMps1 partly suppressed
      apoptosis. Together, these data indicate that the high expression of mitotic
      genes in p53MUT cells after SN-38 treatment contributes to DNA damage-induced
      apoptosis, whereas their suppression in p53WT cells acts as a safeguard mechanism
      preventing mitosis initiation and the subsequent apoptosis. hMps1 kinase is one
      of the mitotic checkpoint proteins whose expression after DNA damage in p53MUT
      cells activates the checkpoint and contributes to apoptosis.

PMID- 16446376
TI  - Efficacy and safety of twice-daily pharmacokinetically enhanced
      amoxicillin/clavulanate (2000/125 mg) in the treatment of adults with community
      acquired pneumonia in a country with a high prevalence of penicillin-resistant
      Streptococcus pneumoniae.
AB  - OBJECTIVES: This randomized, double-blind, non-inferiority trial evaluated the
      efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate
      2000/125 mg twice daily versus amoxicillin/clavulanate 875/125 mg three times
      daily, both given orally for 7 or 10 days, in the treatment of adults with
      community-acquired pneumonia in Spain, a country with a high prevalence of
      penicillin-resistant Streptococcus pneumoniae. PATIENTS AND METHODS: Following
      2:1 randomization, 566 patients (intent-to-treat population) received either
      amoxicillin/clavulanate 2000/125 mg (n = 374) or amoxicillin/clavulanate 875/125
      mg (n = 192). RESULTS: Among the patients who did not deviate from the protocol
      (clinical per-protocol population), clinical success at day 21-28 post-therapy
      (test of cure; primary efficacy endpoint) was 92.4% (266/288) for
      amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for
      amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence
      interval, -4.4, 6.6). Bacteriological success at test of cure in the bacteriology
      per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125
      mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment
      difference 4.8; 95% confidence interval, -6.6, 16.2). At test of cure,
      amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically
      effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC > or = 2
      mg/L) isolates (including three amoxicillin non-susceptible strains) and
      amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one
      amoxicillin non-susceptible strain). CONCLUSIONS: Both treatment regimens were
      well tolerated. Amoxicillin/clavulanate 2000/125 mg was at least as effective
      clinically and as safe as amoxicillin/clavulanate 875/125 mg in the treatment of
      community-acquired pneumonia in adults in a country with a high prevalence of
      penicillin-resistant S. pneumoniae and has a more convenient twice daily
      posology.

PMID- 16446377
TI  - Antiretroviral activity and safety of lopinavir/ritonavir in protease inhibitor
      experienced HIV-infected children with severe-moderate immunodeficiency.

PMID- 16446380
TI  - Essential role of the T cell-specific adapter protein in the activation of LCK in
      peripheral T cells.
AB  - T cell-specific adapter protein (TSAd) is a SRC-homology-2 (SH2) domain
      containing intracellular signaling molecule that is required for T cell antigen
      receptor (TCR)-induced cytokine synthesis in T cells. How TSAd functions in TCR
      signal transduction is not clear. Previous work has suggested a nuclear role for
      this adapter. However, other evidence suggests that TSAd also functions in the
      cytoplasm. Using T cells from TSAd-deficient mice, we now show that the major
      role of TSAd in the cytoplasm is in activation of the LCK protein tyrosine kinase
      at the outset of TCR signal transduction. Consequently, TSAd regulates several
      downstream signaling events, including intracellular calcium mobilization and
      activation of the Ras-extracellular signal-regulated kinase signaling pathway.
      TSAd regulates LCK activity directly through physical interaction with LCK SH3
      and SH2 domains. These studies reveal TSAd as a positive regulator of proximal
      TCR signal transduction and provide important new information on the mechanism of
      TCR-induced LCK activation.

PMID- 16446378
TI  - Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate
      joint inflammation in mouse collagen-induced arthritis.
AB  - Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the
      synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2
      in RA has been well studied, how much PGI2 contributes to RA is little known. To
      examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the
      DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP
      deficient (IP-/-) mice exhibited significant reduction in arthritic scores
      compared with wild-type (WT) mice, despite anti-collagen antibody production and
      complement activation similar to WT mice. IP-/- mice also showed significant
      reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in
      arthritic paws. Consistently, the addition of an IP agonist to cultured synovial
      fibroblasts significantly enhanced IL-6 production and induced expression of
      other arthritis-related genes. On the other hand, loss or inhibition of each PGE
      receptor subtype alone did not affect elicitation of inflammation in CIA.
      However, a partial but significant suppression of CIA was achieved by the
      combined inhibition of EP2 and EP4. Our results show significant roles of both
      PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that
      inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA
      symptoms.

PMID- 16446379
TI  - B cell-deficient NOD.H-2h4 mice have CD4+CD25+ T regulatory cells that inhibit
      the development of spontaneous autoimmune thyroiditis.
AB  - Wild-type (WT) NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT)
      when given 0.05% NaI in their drinking water, whereas B cell-deficient NOD.H-2h4
      mice are SAT resistant. To test the hypothesis that resistance of B cell
      deficient mice to SAT was due to the activity of regulatory CD4+CD25+ T (T reg)
      cells activated if autoantigen was initially presented on non-B cells, CD25+ T
      reg cells were transiently depleted in vivo using anti-CD25. B cell-deficient
      NOD.H-2h4 mice given three weekly injections of anti-CD25 developed SAT 8 wk
      after NaI water. Thyroid lesions were similar to those in WT mice except there
      were no B cells in thyroid infiltrates. WT and B cell-deficient mice had similar
      numbers of CD4+CD25+Foxp3+ cells. Mice with transgenic nitrophenyl-specific B
      cells unable to secrete immunoglobulin were also resistant to SAT, and transient
      depletion of T reg cells resulted in severe SAT with both T and B cells in
      thyroid infiltrates. T reg cells that inhibit SAT were eliminated by day 3
      thymectomy, indicating they belong to the subset of naturally occurring T reg
      cells. However, T reg cell depletion did not increase SAT severity in WT mice,
      suggesting that T reg cells may be nonfunctional when effector T cells are
      activated; i.e., by autoantigen-presenting B cells.

PMID- 16446381
TI  - A checkpoint for autoreactivity in human IgM+ memory B cell development.
AB  - Autoantibodies are removed from the repertoire at two checkpoints during B cell
      development in the bone marrow and the periphery. Despite these checkpoints, up
      to 20% of the antibodies expressed by mature naive B cells in healthy humans show
      low levels of self-reactivity. To determine whether self-reactive antibodies are
      also part of the antigen-experienced memory B cell compartment, we analyzed
      recombinant antibodies cloned from single circulating human IgM+ memory B cells.
      Cells expressing antibodies specific for individual bacterial polysaccharides
      were expanded in the IgM+ memory compartment. In contrast, B cells expressing
      self-reactive and broadly bacterially reactive antibodies were removed from the
      repertoire in the transition from naive to IgM+ memory B cell. Selection against
      self-reactive antibodies was implemented before the onset of somatic
      hypermutation. We conclude that a third checkpoint selects against self
      reactivity during IgM+ memory B cell development in humans.

PMID- 16446382
TI  - All is not Toll: new pathways in DNA recognition.
AB  - Immunological defense depends on the ability of the innate immune system to
      recognize invading microbes as foreign and thus eliminate them. The Toll-like
      receptors (TLRs) help detect foreign invaders by sensing various pathogen
      associated molecules, including microbial RNA and DNA. At present, it is unclear
      whether and how the immune system distinguishes between microbial and self
      nucleic acids, as host-derived RNA and DNA also stimulate TLRs. In addition,
      recent studies have revealed the existence of TLR-independent pathways that are
      activated in response to microbial and host nucleic acids.

PMID- 16446385
TI  - Insulin resistance in preeclampsia.

PMID- 16446386
TI  - Preeclampsia in lean normotensive normotolerant pregnant women can be predicted
      by simple insulin sensitivity indexes.
AB  - Certain similarities between preeclampsia and insulin resistance syndrome suggest
      a possible link between the 2 diseases. The aim of our study was to evaluate 3
      insulin sensitivity (IS) indexes (fasting homeostasis model assessment IS
      [ISHOMA], quantitative insulin sensitivity check index [ISQUICKI], and oral
      glucose IS [OGIS]) early and late in pregnancy in a large number of normotensive
      pregnant women with a normal glucose tolerance and to test the ability of these
      indexes to predict the risk of subsequent preeclampsia. In all, 829 pregnant
      women were tested with a 75-g, 2-hour oral glucose load in 2 periods of
      pregnancy: early (16 to 20 weeks) and late (26 to 30 weeks). In early and late
      pregnancy, respectively, IS(HOMA) was 1.23+/-0.05 and 1.44+/-0.05 (P<0.01),
      IS(QUICKI) was 0.40+/-0.002 and 0.38+/-0.002 (P<0.01), and OGIS was 457+/-2.4 mL
      min(-1) m(-2) and 445+/-2.2 (P<0.001), all confirming the reduction in insulin
      sensitivity during pregnancy. Preeclampsia developed in 6.4% of the pregnant
      women and correlated positively with the 75th centile of IS(HOMA) (P=0.001), with
      a sensitivity of 79% in the early and 83% in the late period and a specificity of
      97% in both. IS(QUICKI) <25th centile was also related with preeclampsia
      (P=0.001), with a sensitivity of 85% in the early and 88% in the late period and
      a specificity of 97% in both. Judging from our findings, ISHOMA and ISQUICKI are
      simple tests that can pinpoint impaired insulin sensitivity early in the
      pregnancy. Given their high sensitivity and specificity, these indexes could be
      useful in predicting the development of preeclampsia in early pregnancy, before
      the disease become clinically evident.

PMID- 16446384
TI  - Electrophysiological characterization and modeling of the structure activity
      relationship of the human concentrative nucleoside transporter 3 (hCNT3).
AB  - We characterized the electrophysiology, kinetics, and quantitative structure
      activity relationship (QSAR) of the human concentrative nucleoside transporter 3
      (hCNT3) expressed in Xenopus laevis oocytes by measuring substrate-induced inward
      currents using a two-microelectrode voltage-clamp system. At membrane potentials
      between -30 and -150 mV, sodium activation of gemcitabine transport was
      sigmoidal, with a K0.5 of 8.5+/-0.3 mM for Na+ and a Hill coefficient of 2.2+/
      0.25 independent of membrane potential. We measured the Imax and K0.5 for
      substrate at -50 mV for the nucleoside analog drugs gemcitabine (638+/-58 nA,
      59.7+/-17.5 microM), ribavirin (546+/-37 nA, 61.0+/-13.2 microM), AZT (420+/-4
      nA, 310+/-9 microM), and 3-deazauridine (506+/-30 nA, 50.8+/-9.90 microM). K0.5
      and Imax for substrate were dependent on membrane potential (both increasing as
      the membrane became more hyperpolarized) for all four drugs. hCNT3 also exhibited
      pre-steady-state currents. The quantitative structure-activity relationship
      (QSAR) was examined using comparative molecular field analysis and comparative
      molecular similarity indices analysis of the inward currents induced by 27
      nucleoside analogs with substitutions at both the ribose and the nucleobase. Two
      statistically significant QSAR models identified electrostatic interaction as the
      major force in hCNT3 transport and attributed a critical role to the 3'-hydroxyl
      position of hCNT3 substrates. Steric hindrance at the 3-position and positive
      charge at the 5-position of the pyrimidine ring were favorable for transport. Two
      hCNT3 pharmacophore models revealed the minimal features required for hCNT3
      transport as two hydrogen bond acceptors at 3'-OH and 5'-O and the hydrophobic
      center occupied by the base ring.

PMID- 16446387
TI  - Prehypertension, diabetes, and cardiovascular disease risk in a population-based
      sample: the Strong Heart Study.
AB  - There are few data about the impact of the recently-defined category of
      prehypertension (systolic blood pressure 120 to 139 mm Hg or diastolic blood
      pressure 80 to 89 mm Hg) on cardiovascular disease incidence. It is also unknown
      whether this association differs between individuals with or without diabetes. A
      total of 2629 Strong Heart Study participants free from hypertension and
      cardiovascular disease at baseline examination were followed for 12 years to
      observe incident cardiovascular disease. Approximately 42% of the 2629
      participants had diabetes. We assessed the prevalence of prehypertension and the
      hazard ratios of incident cardiovascular disease associated with prehypertension.
      Prehypertension was more prevalent in diabetic than nondiabetic participants
      (59.4% versus 48.2%, P<0.001 adjusted for age). Compared with nondiabetic
      participants with normal blood pressure, the hazard ratios of cardiovascular
      disease were 3.70 (95% confidence interval: 2.66, 5.15) for those with both
      prehypertension and diabetes, 1.80 (1.28, 2.54) for those with prehypertension
      alone and 2.90 (2.03, 4.16) for those with diabetes alone. Impaired glucose
      tolerance or impaired fasting glucose also greatly increased the cardiovascular
      disease risk in prehypertensive people. Clinical investigation of more aggressive
      interventions, such as drug treatment for blood pressure control for
      prehypertensive individuals with impaired fasting glucose, impaired glucose
      tolerance, or diabetes is warranted.

PMID- 16446391
TI  - Activating mutation of the renal epithelial chloride channel ClC-Kb predisposing
      to hypertension.

PMID- 16446383
TI  - Block of C/EBP alpha function by phosphorylation in acute myeloid leukemia with
      FLT3 activating mutations.
AB  - Mutations constitutively activating FLT3 kinase are detected in approximately 30%
      of acute myelogenous leukemia (AML) patients and affect downstream pathways such
      as extracellular signal-regulated kinase (ERK)1/2. We found that activation of
      FLT3 in human AML inhibits CCAAT/enhancer binding protein alpha (C/EBPalpha)
      function by ERK1/2-mediated phosphorylation, which may explain the
      differentiation block of leukemic blasts. In MV4;11 cells, pharmacological
      inhibition of either FLT3 or MEK1 leads to granulocytic differentiation.
      Differentiation of MV4;11 cells was also observed when C/EBPalpha mutated at
      serine 21 to alanine (S21A) was stably expressed. In contrast, there was no
      effect when serine 21 was mutated to aspartate (S21D), which mimics
      phosphorylation of C/EBPalpha. Thus, our results suggest that therapies targeting
      the MEK/ERK cascade or development of protein therapies based on transduction of
      constitutively active C/EBPalpha may prove effective in treatment of FLT3 mutant
      leukemias resistant to the FLT3 inhibitor therapies.

PMID- 16446388
TI  - Early phenotypic changes in hypertension: a role for the autonomic nervous system
      and heredity.

PMID- 16446389
TI  - Sympathetic activity and cardiovascular risk factors in young men in the low,
      normal, and high blood pressure ranges.
AB  - We hypothesized that resting blood pressure is related to sympathetic activity in
      young men who are unaware of their blood pressure status in high, normal, and low
      ranges and that there is a relationship between sympathetic activity and coronary
      risk factors. Forty-three healthy, young men from the 1st [group 1, 106/52+/-2/2
      mm Hg (+/-SEM), n=15], 50th (group 2, 129/79+/-2/1 mm Hg, n=15), and 98th to 99th
      percentile (group 3, 166/97+/-3/1 mm Hg, n=13) at a blood pressure screening were
      studied with intraarterial blood pressure, heart rate, and arterial plasma
      catecholamine responses to a mental, cold pressor, and orthostatic stress test.
      At baseline, group 3 had significant higher blood pressure (137/74+/-3/2 mm Hg)
      than group 2 (126/66+/-3/2 mm Hg; P<0.01) and group 1 (116/62+/-2/1 mm Hg;
      P<0.001). Group 1 had lower systolic blood pressure than group 2 (P=0.007).
      Baseline epinephrine and norepinephrine showed a clear positive linear trend
      (P<0.05), with the lowest values being in group 1 and highest in group 3. High
      density lipoprotein was negatively related to epinephrine (r=-0.387; P=0.010).
      Mental stress was the only test that showed significant differences in
      cardiovascular and sympathetic responses among the groups, where group 3 had a
      more pronounced response in systolic and diastolic blood pressure and heart rate
      compared with group 1 (P<0.001) and group 2 (P<0.01). Furthermore, we found
      significant positive linear trends for Deltacatecholamines during mental stress
      across the groups (Deltaepinephrine P=0.001 and Deltanorepinephrine P=0.026,
      ANOVA). We conclude that resting blood pressure reflects both variation in
      resting arterial catecholamines and variation in cardiovascular and sympathetic
      responses specifically to mental stress.

PMID- 16446392
TI  - Individualized therapy for hypertension.

PMID- 16446393
TI  - Evidence supporting a functional role for intracellular renin in the brain.
AB  - The brain renin-angiotensin system is implicated in the regulation of blood
      pressure (BP) and fluid homeostasis. Recent studies reveal that 2 forms of renin
      are expressed in the brain of rodents and humans: secreted prorenin and a
      nonsecreted intracellular form of active renin (icREN). Although the
      intracellular action of renin has long been postulated, no data supporting its
      role in BP regulation has been reported. Therefore, we directly evaluated whether
      this form of renin has physiological implications for BP regulation by
      characterizing transgenic mice expressing human icREN driven by the glial
      fibrillary acidic protein (GFAP) promoter and comparing it with similar mice
      expressing the secreted form of renin. GFAP-icREN mice express hREN primarily in
      the brain and at the same level of expression as GFAP-secreted prorenin. Unlike
      the secreted form, which can be detected in cerebrospinal fluid, no human renin
      could be detected in the cerebrospinal fluid of GFAP-icREN mice. GFAP-icREN mice
      were then bred with transgenic mice expressing human angiotensinogen, also driven
      by the GFAP promoter. Double-transgenic mice expressing either the intracellular
      renin (2.0+/-0.12 mL/10 g/day) or secreted renin (2.8+/-0.3 mL/10 g/day)
      exhibited an increase in drinking volume compared with nontransgenic littermates
      (1.5+/-0.1 mL/10 g/day). Both models exhibited an increase in mean arterial
      pressure (137+/-5 and 133+/-8 mm Hg, respectively) compared with control
      littermates (115+/-3 mm Hg), which could be rapidly reduced after ICV injection
      of losartan. These data support the concept of an intracellular form of renin in
      the brain, which may provoke functional changes in fluid homeostasis and BP
      regulation.

PMID- 16446394
TI  - Chlorthalidone: has it always been the best thiazide-type diuretic?

PMID- 16446395
TI  - Approaches to establishing angiotensin II as a neurotransmitter revisited.

PMID- 16446400
TI  - Blood pressure reactivity to psychological stress and coronary calcification in
      the Coronary Artery Risk Development in Young Adults Study.
AB  - A longstanding hypothesis is that individuals who exhibit large increases in
      blood pressure during psychological stress are at risk for atherosclerosis. We
      tested whether blood pressure changes during psychological stress predict
      subsequent coronary calcification (CaC) in young healthy adults. We evaluated
      2816 healthy black and white women, 20 to 35 years of age, from the Coronary
      Artery Risk Development in Young Adults Study, who were not using medication for
      hypertension or diabetes in 1987-1988. Participants completed video game and star
      tracing tasks while their blood pressure was recorded. Thirteen years later (2000
      2001), they completed computed tomography measures of CaC. Overall 9.3% (261 of
      2816) had CaC present at follow-up. Each 10 mm Hg change in systolic blood
      pressure during the video game was associated with a 24% increased odds of having
      CaC at follow-up (unadjusted odds ratio, 1.24; 95% CI, 1.06 to 1.46; P=0.008).
      This association persisted after adjustment for age, race, sex, education,
      smoking, alcohol, family history of myocardial infarction, smoking, daily alcohol
      consumption, body mass index, and resting or baseline blood pressure (odds ratio,
      1.31; 95% CI, 1.08 to 1.58; P=0.006). Blood pressure changes during the star
      tracing task were not associated with subsequent CaC. Blood pressure changes
      during a video game predicted the presence of CaC 13 years later. To our
      knowledge, this is the first study that reports blood pressure reactivity to a
      stressor being related to calcification in the coronary arteries. Blood pressure
      reactivity may provide useful prognostic information about future risk beyond
      standard risk factors.

PMID- 16446398
TI  - Carotid and aortic stiffness: determinants of discrepancies.
AB  - Several studies have shown that aortic stiffness was an independent predictor for
      cardiovascular events. However, data are less consistent concerning carotid
      stiffness. We analyzed the determinants of the discrepancies between aortic and
      carotid stiffness in different populations with contrasting cardiovascular risk
      factors: 94 healthy normotensives (NT), 243 nondiabetic hypertensives (HT), and
      126 patients with hypertension and type 2 diabetes (T2D). Aortic stiffness was
      measured with carotid-femoral pulse wave velocity. Common carotid stiffness was
      determined from the relative stroke change in diameter (measured with a high
      resolution echotracking system) and carotid pulse pressure (measured with
      applanation tonometry) and was expressed in the same dimensions as pulse wave
      velocity (m/s). We identified the various factors explaining the discrepancies
      between aortic and carotid stiffness by multivariate analysis of the residuals of
      the correlation between aortic and carotid stiffness. The strength of the
      correlation between aortic and carotid stiffness became weaker as the number of
      cardiovascular risk factors increased (NT, r2=0.41; HT, r2=0.16; and T2D,
      r2=0.11), whereas we observed the opposite for the discrepancies (residuals)
      between aortic and carotid stiffness, of which an increasing part was explained
      (11% in NT, 22% in HT, and 45% in T2D) primarily by aging. In conclusion,
      although carotid-femoral pulse wave velocity and carotid stiffness provided
      similar information on the impact of aging on large artery stiffness in normal
      subjects, this was not the case for high blood pressure and/or diabetes. In these
      cases, the aorta stiffened more than the carotid artery with age and other
      cardiovascular risk factors.

PMID- 16446397
TI  - Central role for the cardiotonic steroid marinobufagenin in the pathogenesis of
      experimental uremic cardiomyopathy.
AB  - Patients with chronic renal failure develop a "uremic" cardiomyopathy
      characterized by diastolic dysfunction, cardiac hypertrophy, and systemic oxidant
      stress. Patients with chronic renal failure are also known to have increases in
      the circulating concentrations of the cardiotonic steroid marinobufagenin (MBG).
      On this background, we hypothesized that elevations in circulating MBG may be
      involved in the cardiomyopathy. First, we observed that administration of MBG (10
      microg/kg per day) for 4 weeks caused comparable increases in plasma MBG as
      partial nephrectomy at 4 weeks. MBG infusion caused increases in conscious blood
      pressure, cardiac weight, and the time constant for left ventricular relaxation
      similar to partial nephrectomy. Decreases in the expression of the cardiac
      sarcoplasmic reticulum ATPase, cardiac fibrosis, and systemic oxidant stress were
      observed with both MBG infusion and partial nephrectomy. Next, rats were actively
      immunized against a MBG-BSA conjugate or BSA control, and partial nephrectomy was
      subsequently performed. Immunization against MBG attenuated the cardiac
      hypertrophy, impairment of diastolic function, cardiac fibrosis, and systemic
      oxidant stress seen with partial nephrectomy without a significant effect on
      conscious blood pressure. These data suggest that the increased concentrations of
      MBG are important in the cardiac disease and oxidant stress state seen with renal
      failure.

PMID- 16446399
TI  - Chronic antioxidant supplementation impairs coronary endothelial function and
      myocardial perfusion in normal pigs.
AB  - Experimental studies have shown the beneficial effects of antioxidant
      supplementation on endothelial function in the presence of increased endogenous
      oxidative stress, whereas limited data are available under normal conditions. The
      present study tested the hypothesis that in normal pigs long-term antioxidants
      would have deleterious effects on the cardiovascular system. Normal domestic pigs
      (V, n=6) were studied 12 weeks after dietary supplementation with vitamin E (100
      IU/kg per day) and vitamin C (1 g/day) and compared with normal controls (C,
      n=7). Myocardial perfusion and permeability index were evaluated by electron beam
      computed tomography after intravenous adenosine and dobutamine. Coronary
      endothelial function was evaluated in vitro by organ chamber and coronary tissue
      studied by immunoblotting and staining. Myocardial perfusion response was lower
      in V than in C after adenosine (10.1+/-4.5 versus 53.4+/-5.2%; P<0.01) and
      dobutamine (V, 78.4+/-8.1; C, 193.0+/-39.0%; P<0.05). The permeability index
      increased in V after adenosine (48.8+/-5.1%) and dobutamine (59.9+/-13.6%) and
      did not change in C. Coronary vasodilation to bradykinin and substance P was
      lower in V than in C. Moreover, in V, coronary nitrotyrosine and superoxide
      content was significantly higher than in C. The groups had similar total monomer
      expression of endothelial nitric oxide synthase, whereas the dimerized form,
      reflecting coupled enzyme, was lower in V. These findings suggest that long-term
      experimental antioxidant vitamin supplementation in normal pigs impairs
      myocardial perfusion and coronary endothelial function via an increased level of
      oxidative stress in the arterial wall, which may be partly related to the
      uncoupling of endothelial nitric oxide synthase and/or the direct prooxidant
      effect of vitamin radicals.

PMID- 16446402
TI  - Evidence that hydrogen sulfide is a genotoxic agent.
AB  - Hydrogen sulfide (H2S) produced by commensal sulfate-reducing bacteria, which are
      often members of normal colonic microbiota, represents an environmental insult to
      the intestinal epithelium potentially contributing to chronic intestinal
      disorders that are dependent on gene-environment interactions. For example,
      epidemiologic studies reveal either persistent sulfate-reducing bacteria
      colonization or H2S in the gut or feces of patients suffering from ulcerative
      colitis and colorectal cancer. However, a mechanistic model that explains the
      connection between H2S and ulcerative colitis or colorectal cancer development
      has not been completely formulated. In this study, we examined the chronic
      cytotoxicity of sulfide using a microplate assay and genotoxicity using the
      single-cell gel electrophoresis (SCGE; comet assay) in Chinese hamster ovary
      (CHO) and HT29-Cl.16E cells. Sulfide showed chronic cytotoxicity in CHO cells
      with a %C1/2 of 368.57 micromol/L. Sulfide was not genotoxic in the standard SCGE
      assay. However, in a modified SCGE assay in which DNA repair was inhibited, a
      marked genotoxic effect was observed. A sulfide concentration as low as 250
      micromol/L (similar to that found in human colon) caused significant genomic DNA
      damage. The HT29-Cl.16E colonocyte cell line also exhibited increased genomic DNA
      damage as a function of Na2S concentration when DNA repair was inhibited,
      although these cells were less sensitive to sulfide than CHO cells. These data
      indicate that given a predisposing genetic background that compromises DNA
      repair, H2S may lead to genomic instability or the cumulative mutations found in
      adenomatous polyps leading to colorectal cancer.

PMID- 16446396
TI  - Enhanced vasoreactivity and its response to antihypertensive therapy in
      hypertensive elderly women.
AB  - Several previous studies have demonstrated sex differences in cardiovascular
      autonomic control in healthy young women, but little is known about the
      regulation of blood pressure in hypertensive elderly women, who have the greatest
      risk of adverse cardiovascular events. Therefore, we examined sex differences in
      physiological responses to upright tilt in 21 healthy (13 men and 8 women), 22
      controlled hypertensive (10 men and 12 women), and 18 uncontrolled hypertensive
      (9 men and 9 women) elderly men and women. Of these, 19 normotensives, 18
      controlled hypertensives, and 14 uncontrolled hypertensives completed 6 months of
      observation or pharmacological therapy for uncontrolled hypertension. All of the
      subjects underwent continuous monitoring of cardiac (RR) interval (ECG), finger
      arterial pressure (photoplethysmography), and stroke volume (transthoracic
      impedance) and periodic measurements of forearm blood flow (venous occlusion
      plethysmography) while resting supine and during a graded head-up tilt. Blood
      pressure and RR-interval power spectra were computed. Baroreflex gain was
      estimated by the cross-spectral and sequence methods. In contrast to other
      groups, elderly hypertensive women increased systemic vascular resistance during
      tilt. This response was associated with greater low-frequency systolic pressure
      variability, a presumed marker of sympathetic vascular control. After 6 months of
      successful antihypertensive therapy, women showed attenuation of the systemic
      vascular resistance response and a reduction in low-frequency systolic blood
      pressure variability to levels similar to men and normotensive controls. These
      results highlight the beneficial effects of antihypertensive therapy on the
      systemic vasculature, particularly for elderly women in whom enhanced
      vasoreactivity may contribute to excessive cardiovascular morbidity and
      mortality.

PMID- 16446403
TI  - Ubiquitination of p53 at multiple sites in the DNA-binding domain.
AB  - The tumor suppressor p53 is negatively regulated by the ubiquitin ligase MDM2.
      The MDM2 recognition site is at the NH2-terminal region of p53, but the positions
      of the actual ubiquitination acceptor sites are less well defined. Lysine
      residues at the COOH-terminal region of p53 are implicated as sites for
      ubiquitination and other post-translational modifications. Unexpectedly, we found
      that substitution of the COOH-terminal lysine residues did not diminish MDM2
      mediated ubiquitination. Ubiquitination was not abolished even after the entire
      COOH-terminal regulatory region was removed. Using a method involving in vitro
      proteolytic cleavage at specific sites after ubiquitination, we found that p53
      was ubiquitinated at the NH2-terminal portion of the protein. The lysine residue
      within the transactivation domain is probably not essential for ubiquitination,
      as substitution with an arginine did not affect MDM2 binding or ubiquitination.
      In contrast, several conserved lysine residues in the DNA-binding domain are
      critical for p53 ubiquitination. Removal of the DNA-binding domain reduced
      ubiquitination and increased the stability of p53. These data provide evidence
      that in addition to the COOH-terminal residues, p53 may also be ubiquitinated at
      sites in the DNA-binding domain.

PMID- 16446401
TI  - Epigenetic heterogeneity of high-grade prostatic intraepithelial neoplasia: clues
      for clonal progression in prostate carcinogenesis.
AB  - High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor
      of prostate adenocarcinoma, but the frequency and timing of epigenetic changes
      found in prostate carcinogenesis has not been extensively documented. Thus, the
      promoters of three genes (APC, GSTP1, and RARbeta2) involved in prostate
      carcinogenesis were tested by quantitative methylation-specific PCR in tissue DNA
      from 30 prostate carcinomas, 128 high-grade PIN lesions, and 30 normal prostate
      tissue samples dissected from 30 radical prostatectomy specimens using laser
      capture microdissection. The percentage of methylated alleles (PMA) was
      calculated for each gene, and hierarchical cluster analysis was used to define
      the degree of similarity of epigenetic alterations among the various samples. We
      found that PMA values of APC and RARbeta2 were higher than those of GSTP1 in all
      three types of tissue samples and median PMA values for all three genes were
      higher in prostate cancer. By cluster analysis, 26 of 30 prostate carcinomas and
      82 of 128 high-grade PIN lesions were grouped in the "high methylation" branch,
      whereas 24 of 30 normal prostate tissue samples were allocated in the "low
      methylation" branch. Although high-grade PIN lesions are epigenetically more
      similar to prostate carcinoma than to normal prostate tissue, paired prostate
      carcinoma and high-grade PIN lesions did not always segregate together. We
      concluded that APC and RARbeta2 hypermethylation is frequent in normal prostate
      tissue and the progressive enrichment in cells carrying methylated alleles
      observed in high-grade PIN and prostate carcinoma is consistent with clonal
      progression. Because GSTP1 promoter methylation is mainly observed in prostate
      carcinoma and some high-grade PIN lesions, it represents an important marker for
      the transition of in situ to invasive neoplasia.

PMID- 16446404
TI  - Heregulins implicated in cellular functions other than receptor activation.
AB  - Heregulins (HRG) are known as soluble secreted growth factors that, on binding
      and activating ErbB3 and ErbB4 cell surface receptors, are involved in cell
      proliferation, metastasis, survival, and differentiation in normal and malignant
      tissues. Previous studies have shown that some HRG1 splice variants are
      translocated to the nucleus. By investigating the subcellular localization of
      HRGalpha(1-241), nuclear translocation and accumulation in nuclear dot-like
      structures was shown in breast cancer cells. This subcellular distribution
      pattern depends on the presence of at least one of two nuclear localization
      sequences and on two domains on the HRG construct that were found to be necessary
      for nuclear dot formation. Focusing on the nuclear function of HRG, a mammary
      gland cDNA library was screened with the mature form of HRGalpha in a yeast two
      hybrid system, and coimmunoprecipitation of endogenous HRG was done. The data
      reveal positive interactions of HRGalpha(1-241) with nuclear factors implicated
      in different biological functions, including transcriptional control as
      exemplified by interaction with the transcriptional repressor histone deacetylase
      2. In addition, HRGalpha(1-241) showed transcriptional repression activity in a
      reporter gene assay. Furthermore, a potential of HRG proteins to form homodimers
      was reported and the HRG sequence responsible for dimerization was identified.
      These observations strongly support the notion that HRG1 splice variants have
      multifunctional properties, including previously unknown regulatory functions
      within the nucleus that are different from the activation of ErbB receptor
      signaling.

PMID- 16446405
TI  - A constitutively active Lck kinase promotes cell proliferation and resistance to
      apoptosis through signal transducer and activator of transcription 5b activation.
AB  - Lck is a Src family protein tyrosine kinase and is expressed predominantly in T
      cells. Aberrant expression or activation of Lck kinase has been reported in both
      lymphoid and nonlymphoid malignancies. However, the mechanisms underlying Lck
      mediated oncogenesis remain largely unclear. In this report, we establish a
      tetracycline-inducible system to study the biochemical and biological effects of
      a constitutively active Lck mutant with a point mutation at the negative
      regulatory tyrosine. Expression of the active Lck kinase induces both tyrosine
      phosphorylation and DNA-binding activity of signal transducer and activator of
      transcription 5b (STAT5b), a STAT family member activated in a variety of tumor
      cells. The active Lck kinase interacts with STAT5b in cells, suggesting that Lck
      may directly phosphorylate STAT5b. Expression of the constitutively active Lck
      mutant in interleukin-3 (IL-3)-dependent BaF3 cells promotes cell proliferation.
      In addition, the active Lck kinase protects BaF3 cells from IL-3 withdrawal
      induced apoptotic death and leads to IL-3-independent growth. These transforming
      properties of the oncogenic Lck kinase can be further augmented by expression of
      exogenous wild-type STAT5b but attenuated by a dominant-negative form of STAT5b.
      All together, our results suggest the potential involvement of STAT5b in Lck
      mediated cellular transformation.

PMID- 16446406
TI  - Messenger RNAs under differential translational control in Ki-ras-transformed
      cells.
AB  - Microarrays have been used extensively to identify differential gene expression
      at the level of transcriptional control in oncogenesis. However, increasing
      evidence indicates that changes in translational control are critical to
      oncogenic transformation. This study identifies mRNA transcripts that are
      differentially regulated, primarily at the level of translation, in the
      immortalized human embryonic prostate epithelial cell line 267B1 and the v-Ki-ras
      transformed counterpart by comparing total mRNA to polysome-bound mRNA by using
      Affymetrix oligonucleotide microarrays. Among the transcripts that were
      identified were those encoding proteins involved in DNA replication, cell cycle
      control, cell-to-cell interactions, electron transport, G protein signaling, and
      translation. Many of these proteins are known to contribute to oncogenesis or
      have the potential to contribute to oncogenesis. Differential expression of RNA
      binding proteins and the presence of highly conserved motifs in the 5' and 3'
      untranslated regions of the mRNAs are consistent with multiple pathways and
      mechanisms governing the changes in translational control. Although Alu sequences
      were found to be associated with increased translation in transformed cells, an
      evolutionarily conserved motif was identified in the 3' untranslated regions of
      ephrinB1, calreticulin, integrin alpha3, and mucin3B that was associated with
      decreased polysome association in 267B1/Ki-ras.

PMID- 16446407
TI  - What can neuroscience contribute to ethics?

PMID- 16446408
TI  - On the difficulty of neurosurgical end of life decisions.
AB  - OBJECTIVE: To analyse the process of end of life decisions in a neurosurgical
      environment. METHODS: All 113 neurosurgical patients, who were subject to so
      called end of life decisions within a one year period were prospectively enrolled
      in a computerised data bank. Decision pathways according to patient and physician
      related parameters were assessed. RESULTS: Leading primary diagnoses of the
      patients were traumatic brain injury and intracranial haemorrhage. Forty-five
      patients had undergone an emergency neurosurgical operation prior to end of life
      decision, N = 69 were conservatively treated, which included intracranial
      pressure recording, or they were not offered neurosurgical care because of futile
      prognosis. N = 111 died after a median of two (zero to nine) days. Two, in whom
      the end of life decisions were revised, survived. Clear decisions to terminate
      further treatment were made by a senior staff member on call being informed by
      the senior resident on call (27.4%), difficult decisions on the basis of
      extensive round discussions (71.7%), and very difficult decision by an
      interdisciplinary ethical consult (0.9%). Decisions were further substantiated by
      electrophysiological examinations in N = 59. CONCLUSION: End of life decisions
      are to be considered standard situations for neurosurgeons. These decisions may
      reach a high rate of "positive" prediction, if substantiated by
      electrophysiological examinations as well as on the grounds of clinical
      experience and respect for the assumed will of the patient. The fact that
      patients may survive following revision of an end of life decision underlines the
      necessity for repeated reassessment of these decisions. Ethical training for
      neurosurgeons is to be encouraged.

PMID- 16446409
TI  - Neuroscience of decision making and informed consent: an investigation in
      neuroethics.
AB  - Progress in neuroscience will allow us to reveal the neuronal correlates of
      psychological processes involved in ethically relevant notions such as informed
      consent. Informed consent involves decision making, the psychological and neural
      processes of which have been investigated extensively in neuroscience. The
      neuroscience of decision making may be able to contribute to an ethics of
      informed consent by providing empirical and thus descriptive criteria. Since,
      however, descriptive criteria must be distinguished from normative criteria, the
      neuroscience of decision making cannot replace the ethics of informed consent.
      Instead, the neuroscience of decision making could complement the current ethics,
      resulting in what can be called neuroethics of informed consent. It is concluded
      that current progress in the neurosciences could complement and change the way in
      which we approach ethical problems in neuropsychiatry.

PMID- 16446410
TI  - Psychopharmacology and memory.
AB  - Psychotropic and other drugs can alter brain mechanisms regulating the formation,
      storage, and retrieval of different types of memory. These include "off label"
      uses of existing drugs and new drugs designed specifically to target the neural
      bases of memory. This paper discusses the use of beta-adrenergic antagonists to
      prevent or erase non-conscious pathological emotional memories in the amygdala.
      It also discusses the use of novel psychopharmacological agents to enhance long
      term semantic and short term working memory by altering storage and retrieval
      mechanisms in the hippocampus and prefrontal cortex. Although intervention in the
      brain to alter memory as therapy or enhancement holds considerable promise, the
      long term effects of experimental drugs on the brain and memory are not known.
      More studies are needed to adequately assess the potential benefits and risks of
      these interventions.

PMID- 16446411
TI  - Cyborgs and moral identity.
AB  - Neuroscience and technological medicine in general increasingly faces us with the
      imminent reality of cyborgs-integrated part human and part machine complexes. If
      my brain functions in a way that is supported by and exploits intelligent
      technology both external and implantable, then how should I be treated and what
      is my moral status-am I a machine or am I a person? I explore a number of
      scenarios where the balance between human and humanoid machine shifts, and ask
      questions about the moral status of the individuals concerned. The position taken
      is very much in accordance with the Aristotelian idea that our moral behaviour is
      of a piece with our social and personal skills and forms a reactive and
      reflective component of those skills.

PMID- 16446412
TI  - Animal rights, animal minds, and human mindreading.
AB  - Do non-human animals have rights? The answer to this question depends on whether
      animals have morally relevant mental properties. Mindreading is the human
      activity of ascribing mental states to other organisms. Current knowledge about
      the evolution and cognitive structure of mindreading indicates that human
      ascriptions of mental states to non-human animals are very inaccurate. The
      accuracy of human mindreading can be improved with the help of scientific studies
      of animal minds. However, the scientific studies do not by themselves solve the
      problem of how to map psychological similarities (and differences) between humans
      and animals onto a distinction between morally relevant and morally irrelevant
      mental properties. The current limitations of human mindreading-whether
      scientifically aided or not-have practical consequences for the rational
      justification of claims about which rights (if any) non-human animals should be
      accorded.

PMID- 16446413
TI  - When psychiatry and bioethics disagree about patient decision making capacity
      (DMC).
AB  - The terms "competency" and "decision making capacity" (DMC) are often used
      interchangeably in the medical setting. Although competency is a legal
      determination made by judges, "competency" assessments are frequently requested
      of psychiatrists who are called to consult on hospitalised patients who refuse
      medical treatment. In these situations, the bioethicist is called to consult
      frequently as well, sometimes as a second opinion or "tie breaker". The
      psychiatric determination of competence, while a clinical phenomenon, is based
      primarily in legalism and can be quite different from the bioethics approach.
      This discrepancy highlights the difficulties that arise when a patient is found
      to be "competent" by psychiatry but lacking in DMC by bioethics. Using a case,
      this dilemma is explored and guidance for reconciling the opinions of two
      distinct clinical specialties is offered.

PMID- 16446414
TI  - Mental disorder ethics: theory and empirical investigation.
AB  - Mental disorders and their care present unusual problems within biomedical
      ethics. The disorders themselves invite an ethical critique, as does society's
      attitude to them; researching the diagnosis and treatment of mental disorders
      also presents special ethical issues. The current high profile of mental disorder
      ethics, emphasised by recent political and legal developments, makes this a field
      of research that is not only important but also highly topical. For these
      reasons, the Wellcome Trust's biomedical ethics programme convened a meeting,
      "Investigating Ethics and Mental Disorders", in order to review some current
      research, and to stimulate topics and methods of future research in the field.
      The meeting was attended by policy makers, regulators, research funders, and
      researchers, including social scientists, psychiatrists, psychologists, lawyers,
      philosophers, criminologists, and others. As well as aiming to inspire a stronger
      research endeavour, the meeting also sought to stimulate an improved
      understanding of the methods and interactions that can contribute to "empirical
      ethics" generally. This paper reports on the meeting by describing contributions
      from individual speakers and discussion sections of the meeting. At the end we
      describe and discuss the conclusions of the meeting. As a result, the text is
      referenced less than would normally be expected in a review. Also, in summarising
      contributions from named presenters at the meeting it is possible that we have
      created inaccuracies; however, the definitive version of each paper, as provided
      directly by the presenter, is available at
      http://www.wellcome.ac.uk/doc.WTX025116.html.

PMID- 16446415
TI  - Medicating the mind: a Kantian analysis of overprescribing psychoactive drugs.
AB  - Psychoactive drugs are being prescribed to millions of Americans at an increasing
      rate. In many cases these drugs are necessary in order to overcome debilitating
      emotional problems. Yet in other instances, these drugs are used to supplant, not
      supplement, interpersonal therapy. The process of overcoming emotional obstacles
      by introspection and the attainment of self knowledge is gradually being eroded
      via the gratuitous use of psychoactive medication in order to rapidly attain a
      release from the common problems that life inevitably presents us with. In this
      paper, I argue that Kant's formula of humanity, which maintains that persons
      ought never to treat others or themselves soley as a means to an end, proscribes
      this. Moreover, Kant argues that we have an imperfect duty of self development,
      and I argue that we fail to adhere to such a duty whenever we seek to evade the
      process of introspection and self knowledge in favour of the expedient results
      that drugs may provide us with as we attempt to overcome the emotional hurdles in
      our lives.

PMID- 16446416
TI  - Stimulating debate: ethics in a multidisciplinary functional neurosurgery
      committee.
AB  - Multidisciplinary healthcare committees meet regularly to discuss patients'
      candidacy for emerging functional neurosurgical procedures, such as Deep Brain
      Stimulation (DBS). Through debate and discussion around the surgical candidacy of
      particular patients, functional neurosurgery programs begin to mold practice and
      policy supported both by scientific evidence and clear value choices. These
      neurosurgical decisions have special considerations not found in non-neurologic
      committees. The professional time used to resolve these conflicts provides
      opportunities for the emergence of careful, ethical practices simultaneous with
      the expansion of therapy applications.

PMID- 16446417
TI  - The promise and predicament of cosmetic neurology.

PMID- 16446419
TI  - Nursing, obedience, and complicity with eugenics: a contextual interpretation of
      nursing morality at the turn of the twentieth century.
AB  - This paper uses Margaret Urban Walker's "expressive collaborative" method of
      moral inquiry to examine and illustrate the morality of nurses in Great Britain
      from around 1860 to 1915, as well as nursing complicity in one of the first
      eugenic policies. The authors aim to focus on how context shapes and limits
      morality and agency in nurses and contributes to a better understanding of
      debates in nursing ethics both in the past and present.

PMID- 16446418
TI  - Does informed consent exempt Japanese doctors from reporting therapeutic deaths?
AB  - The Japanese Medical Act section 21 states that doctors must report unnatural
      deaths to the police, even though the term "unnatural death" is not defined by
      law. However, many doctors are reluctant to report potential therapeutic deaths
      (PTDs). The Japanese Society of Legal Medicine has submitted guidelines for
      unnatural death, including PTD. These define a PTD as an unexpected death, the
      cause of which is unknown, but which is potentially related to medical practice.
      Such deaths are "reportable" to the coroner in the UK. In this study, we
      addressed the question of whether physicians would report each of eight
      hypothetical PTDs. Although the clinical societies (the Japan Society of Internal
      Medicine and the Japan Surgical Society) declare that doctors must report deaths
      due to gross negligence, 60% of the participants said that they would not report
      gross negligence involving an overdose in cases where they had obtained informed
      consent or had provided an explanation after the death occurred. This can be
      accounted for by the mistaken belief on the part of the participants that
      obtaining informed consent exempts Japanese physicians from the duty of reporting
      PTDs. The attitude of Japanese physicians is caused by the death investigation
      system, which is designed to discover whether a crime has been committed rather
      than focusing on the cause of death. Accordingly, the Japanese Government has
      decided to commission a pilot study from an independent organisation in which
      medical specialists will investigate PTDs in order to prevent deaths occurring as
      a result of gross negligence.

PMID- 16446420
TI  - Immortalized keratinocyte lines derived from human embryonic stem cells.
AB  - Cells of the human embryonic stem (hES) cell line H9, when cultured in the form
      of embryoid bodies, give rise to cells with markers of the keratinocyte of
      stratified squamous epithelia. Keratinocytes also form in nodules produced in
      scid mice by injected H9 cells; the hES-derived keratinocytes could be recovered
      in culture, where their colonies underwent a peculiar form of fragmentation.
      Whether formed from embryoid bodies or in nodules, hES-derived keratinocytes
      differed from postnatal keratinocytes in their much lower proliferative potential
      in culture; isolated single keratinocytes could not be expanded into mass
      cultures. Although their growth was not improved by transduction with the hTERT
      gene, these keratinocytes were immortalized by transduction with the E6E7 genes
      of HPV16. Clonally derived lines isolated from E6E7-transduced keratinocytes
      continued to express markers of the keratinocyte lineage, but the frequency with
      which they terminally differentiated was reduced compared with keratinocytes
      cultured from postnatal human epidermis. If other hES-derived somatic cell types
      also prove to be restricted in growth potential, not identical to the
      corresponding postnatal cell types, and to require immortalization for clonal
      isolation and expansion, these properties will have to be considered in planning
      their therapeutic use.

PMID- 16446421
TI  - WNK3 bypasses the tonicity requirement for K-Cl cotransporter activation via a
      phosphatase-dependent pathway.
AB  - SLC12A cation/Cl- cotransporters are mutated in human disease, are targets of
      diuretics, and are collectively involved in the regulation of cell volume,
      neuronal excitability, and blood pressure. This gene family has two major
      branches with different physiological functions and inverse regulation: K-Cl
      cotransporters (KCC1-KCC4) mediate cellular Cl- efflux, are inhibited by
      phosphorylation, and are activated by dephosphorylation; Na-(K)-Cl cotransporters
      (NCC and NKCC1/2) mediate cellular Cl- influx and are activated by
      phosphorylation. A single kinase/phosphatase pathway is thought to coordinate the
      activities of these cotransporters in a given cell; however, the mechanisms
      involved are as yet unknown. We previously demonstrated that WNK3, a paralog of
      serine-threonine kinases mutated in hereditary hypertension, is coexpressed with
      several cation/Cl- cotransporters and regulates their activity. Here, we show
      that WNK3 completely prevents the cell swelling-induced activation of KCC1-KCC4
      in Xenopus oocytes. In contrast, catalytically inactive WNK3 abolishes the cell
      shrinkage-induced inhibition of KCC1-KCC4, resulting in a >100-fold stimulation
      of K-Cl cotransport during conditions in which transport is normally inactive.
      This activation is completely abolished by calyculin A and cyclosporine A,
      inhibitors of protein phosphatase 1 and 2B, respectively. Wild-type WNK3
      activates Na-(K)-Cl cotransporters by increasing their phosphorylation, and
      catalytically inactive kinase inhibits Na-(K)-Cl cotransporters by decreasing
      their phosphorylation, such that our data suggest that WNK3 is a crucial
      component of the kinase/phosphatase signaling pathway that coordinately regulates
      the Cl- influx and efflux branches of the SLC12A cotransporter family.

PMID- 16446422
TI  - Manipulating phospholipids for crystallization of a membrane transport protein.
AB  - Crystallization is a major bottleneck to obtaining x-ray structures of membrane
      proteins. By applying an established crystallization protocol for the lactose
      permease (LacY) of Escherichia coli, a systematic study of the effect of
      phospholipids (PL) on crystallization of LacY was undertaken. We observe three
      different crystal forms that diffract to increasingly better resolution in a
      manner that correlates with the concentration of copurified PL. Consistently,
      progressive addition of E. coli PL to delipidated LacY leads to different crystal
      forms. Tetragonal crystals are obtained with improved diffraction quality for a
      stable mutant by carefully adjusting PL content. Furthermore, crystals of good
      quality from wild-type LacY, a particularly difficult protein, were also obtained
      by using same approach. Thus, it is likely that manipulation of PL is a good
      strategy for predominantly hydrophobic membrane proteins like LacY.

PMID- 16446423
TI  - Differential involvement of the hippocampus, anterior cingulate cortex, and
      basolateral amygdala in memory for context and footshock.
AB  - Extensive evidence from contextual fear conditioning experiments suggests that
      the hippocampus is involved in processing memory for contextual information.
      Evidence also suggests that the rostral anterior cingulate cortex (rACC) may be
      selectively involved in memory for nociceptive stimulation. In contrast, many
      findings indicate that the basolateral amygdala (BLA) is more broadly involved in
      modulating the consolidation of different kinds of information. To investigate
      further the differential involvement of these brain regions in memory
      consolidation, the present experiments used a modified inhibitory avoidance
      training procedure that took place on 2 sequential days to separate context
      training from footshock training. Male Sprague-Dawley rats were implanted with
      unilateral cannulae aimed at the (i) hippocampus, (ii) rACC, or (iii) BLA, and
      given infusions of the muscarinic cholinergic agonist oxotremorine (OXO)
      immediately after either context training (day 1) or footshock training in that
      context (day 2). OXO enhanced retention when infused into the hippocampus after
      context, but not footshock, training. Conversely, OXO infusions enhanced memory
      when administered into the rACC immediately after footshock, but not context,
      training. Lastly, intra-BLA OXO infusions enhanced retention when administered
      after either context or footshock training. These findings are consistent with
      evidence that the hippocampus and rACC play selective roles in memory for
      specific components of training experiences. Additionally, they provide further
      evidence that the BLA is more liberally involved in modulating memory
      consolidation for various aspects of emotionally arousing experiences.

PMID- 16446424
TI  - Activation of phosphatidylinositol 3-kinase signaling by a mutant thyroid hormone
      beta receptor.
AB  - Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B
      signaling pathway has been associated with multiple human cancers. Recently we
      showed that AKT is activated in both the thyroid and metastatic lesions of a
      mouse model of follicular thyroid carcinoma [thyroid hormone beta receptor
      (TRbeta)(PV/PV) mice]. This TRbeta(PV/PV) mouse harbors a knock-in mutant TRbeta
      gene (TRbetaPV mutant) that spontaneously develops thyroid cancer and distant
      metastasis similar to human follicular thyroid cancer. Here we show that in
      thyroid tumors, PV mutant bound significantly more to the PI3K-regulatory subunit
      p85alpha, resulting in a greater increase in the kinase activity than did TRbeta1
      in wild-type mice. By GST pull-down assays, the ligand-binding domain of TR was
      identified as the interaction site with p85alpha. By confocal fluorescence
      microscopy, p85alpha was shown to colocalize with TRbeta1 or PV mainly in the
      nuclear compartment of cultured tumor cells from TRbeta(PV/PV) mice, but
      cytoplasmic p85alpha/PV or p85alpha/TRbeta1 complexes were also detectable.
      Further biochemical analysis revealed that the activation of the PI3K-AKT
      mammalian target of the rapamycin-p70(S6K) pathway was observed in both the
      cytoplasmic and nuclear compartments, whereas the activation of the PI3K-integrin
      linked kinase-matrix metalloproteinase 2 pathway was detected mainly in the
      extranuclear compartments. These results suggest that PV, via the activation of
      p85alpha, could act to affect PI3K downstream signaling in both the nuclear and
      extranuclear compartments, thereby contributing to thyroid carcinogenesis.
      Importantly, the present study unveils a mechanism by which a mutant TR acts to
      activate PI3K activity via protein-protein interactions.

PMID- 16446425
TI  - Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli
      infection but not to ischemia-reperfusion injury.
AB  - Diverse functions have been reported for lipocalin 2. To investigate these
      functions in vivo, we generated gene-targeted lipocalin 2-deficient mice (Lcn2-/-
      mice). In vitro studies have suggested that lipocalin 2 is important for cellular
      apoptosis induced by IL-3 withdrawal, and for the induction of kidney
      differentiation during embryogenesis. Analysis of Lcn2-/- mice showed normal cell
      death upon IL-3 withdrawal and normal kidney development. However, we found that
      Lcn2-/- mice exhibited an increased susceptibility to bacterial infections, in
      keeping with the proposed function of lipocalin 2 in iron sequestration.
      Neutrophils isolated from Lcn2-/- mice showed significantly less bacteriostatic
      activity compared with WT controls. The bacteriostatic property of the WT
      neutrophils was abolished by the addition of exogenous iron, indicating that the
      main function of lipocalin 2 in the antibacterial innate immune response is to
      limit this essential element. Another important function ascribed to lipocalin 2
      has been its protective role against kidney ischemia-reperfusion injury. We
      analyzed Lcn2-/- mice using a mouse model for severe renal failure and could not
      detect any significant differences compared with their WT littermates.

PMID- 16446426
TI  - Activation of anti-hepatitis C virus responses via Toll-like receptor 7.
AB  - IFN-alpha is used to suppress the replication of hepatitis C virus (HCV) in
      chronically infected patients with partial success. Here we present evidence
      showing that a ligand of Toll-like receptor 7 (TLR7) can induce anti-HCV immunity
      not only by IFN induction, but also through an IFN-independent mechanism. Human
      hepatocyte line Huh-7 carrying an HCV replicon expressed TLR7, and activation of
      the receptor induced several antiviral genes including IFN regulatory factor-7.
      Inhibitors of the enzyme inosine monophosphate dehydrogenase augmented both IFN
      dependent and -independent antiviral effect. Prolonged exposure of Huh-7 cells to
      a TLR7 ligand [SM360320 (9-benzyl-8-hydroxy-2-(2-methoxyethoxy)adenine)], alone
      or in combination with an inosine monophosphate dehydrogenase inhibitor, reduced
      HCV levels dose dependently. Immunohistochemical analysis of livers shows that
      TLR7 is expressed in hepatocytes of normal or HCV-infected people. Because TLR7
      agonists can impede HCV infection both via type I IFN and independently of IFN,
      they may be considered as an alternative treatment of chronic HCV infection,
      especially in IFN-alpha-resistant patients.

PMID- 16446427
TI  - Integrins regulate VE-cadherin and catenins: dependence of this regulation on
      Src, but not on Ras.
AB  - Adhesions of cells to extracellular matrix and adjacent cells are mediated by
      integrins and VE-cadherin, respectively. Although these adhesion processes play
      crucial roles in vascular cell migration and angiogenesis, it remains unclear as
      to how they are coordinated to regulate cellular functions. We report here that
      integrin engagement by treating bovine endothelial aortic cell monolayers with
      beads coated with fibronectin (Fn) led to disruption of the VE-cadherin
      containing adherens junctions. This disruption was accompanied by increases of
      tyrosine phosphorylation of beta-catenin, gamma-catenin, and p120ctn, as well as
      the dissociation of alpha-catenin and gamma-catenin from VE-cadherin. We applied
      a membrane-targeted Src reporter based on the fluorescence resonance energy
      transfer technique to visualize the dynamic Src activation at subcellular levels
      in live cells. The integrin engagement induced by Fn-coated beads caused the
      activation of Src around the beads and at adherens junctions, which are
      subsequently disrupted. The inhibition of Src with PP1 blocked the effects of
      integrin engagement on adherens junctions. Although Ras can also modulate
      adherens junctions, the resulting patterns of phosphorylation and association of
      junction proteins were distinct from those induced by integrin engagement. The
      inhibition of Ras by RasN17 did not rescue the disruption of adherens junctions
      induced by integrin engagement or by Src activation. Integrin engagement by Fn
      coated beads also induced a significant alteration of cortical actin filaments at
      adherens junctions. The results indicate that integrin engagement disrupts VE
      cadherin-containing adherens junctions via the activation of Src, but not Ras,
      possibly as a result of modulation of the actin network.

PMID- 16446428
TI  - Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced
      conformational change.
AB  - The E3 ubiquitin (Ub) ligase Itch is a critical regulator of T helper 2 (Th2)
      cytokine production through its ability to induce Ub-dependent JunB degradation.
      After T cell receptor engagement, Itch undergoes JNK1-mediated phosphorylation
      that greatly enhances its enzymatic activity. To investigate how phosphorylation
      activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites
      within Itch as S199, S232, and T222, which are located within a Pro-rich region.
      Phosphorylation of these sites is necessary and sufficient for disrupting an
      inhibitory interaction between the WW domain of Itch and its catalytic HECT
      (Homologous to E6-AP C Terminus) domain and induces a conformational change that
      greatly enhances the catalytic activity of Itch, a HECT E3 ligase found to be
      directly activated upon its phosphorylation.

PMID- 16446429
TI  - The diacylglycerol-binding protein alpha1-chimaerin regulates dendritic
      morphology.
AB  - The morphological and functional differentiation of neuronal dendrites is
      controlled through transcriptional programs and cell-cell signaling. Synaptic
      activity is thought to play an important role in the maturation of dendritic
      arbors, but the signaling pathways that couple neuronal activity and
      morphological changes in dendrites are not well understood. We explored the
      function of alpha1-chimaerin, a neuronal diacylglycerol-binding protein with a
      Rho GTPase-activating protein domain that inactivates Rac1. We find that
      stimulation of phospholipase Cbeta-coupled cell surface receptors recruits alpha1
      chimaerin to the plasma membrane of cultured hippocampal neurons. We further show
      that alpha1-chimaerin protein levels are controlled by synaptic activity and that
      increased alpha1-chimaerin expression results in the pruning of dendritic spines
      and branches. This pruning activity requires both the diacylglycerol-binding and
      Rac GTPase-activating protein activity of alpha1-chimaerin. Suppression of alpha1
      chimaerin expression resulted in increased process growth from the dendritic
      shaft and from spine heads. Our data suggest that alpha1-chimaerin is an activity
      regulated Rho GTPase regulator that is activated by phospholipase Cbeta-coupled
      cell surface receptors and contributes to pruning of dendritic arbors.

PMID- 16446430
TI  - Regulation of blood flow in activated human brain by cytosolic NADH/NAD+ ratio.
AB  - It has been known for more than a century that increases in neuronal activity in
      the brain are reliably accompanied by changes in local blood flow. More recently
      it has been appreciated that these blood flow increases are accompanied by
      increases in glycolysis that are much greater than the increases in oxidative
      phosphorylation. It has been proposed by us and others that this activity-induced
      increase in glycolysis mediates the increase in blood flow by mechanisms linked
      through the near-equilibrium relationship between cytosolic NADH/NAD+ and the
      lactate/pyruvate ratios. Here we show in awake human subjects that by transiently
      raising blood pyruvate concentration during local increases in functional brain
      activity, a maneuver designed to reduce the cytosolic NADH/NAD+ ratio, the
      expected blood flow response measured with positron-emission tomography is
      significantly attenuated. This result provides critical additional support for
      the hypothesis that, like in anesthetized rodents, the cytosolic NADH/NAD+ ratio
      of awake human subjects links activity-induced increases in glycolysis to
      signaling pathways for the regulation of blood flow.

PMID- 16446431
TI  - RNAs induced by Epstein-Barr virus nuclear antigen 2 in lymphoblastoid cell
      lines.
AB  - Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) association with RBP-Jkappa is
      essential for regulation of virus and cell gene transcription and B lymphocyte
      transformation into infinitely proliferating lymphoblastoid cells (LCLs). To
      identify EBNA2-regulated cell genes in LCLs, an EBV recombinant that expresses
      EBNA2 with its C terminus fused in frame to a 4-hydroxytamoxifen (4HT)-dependent
      mutant estrogen receptor (E2HTF) was used to transform primary B lymphocytes to
      LCLs. In the presence of 4HT, E2HTF expression level and effects on the LMP1
      promoter in transfected BJAB lymphoblasts were similar to EBNA2. In 4HT
      supplemented medium, E2HTF EBV recombinant infected LCLs were also similar to
      EBNA2 LCLs in outgrowth but required higher serum and a restricted range of cell
      concentrations for consistent growth. In medium without 4HT, E2HTF localized to
      the cytoplasm, c-myc levels substantially decreased within 6 h, cells stopped
      growing, and levels of other EBNAs and LMP1 remained stable for 24 h. Over this
      24-h period, 30 cell RNAs decreased 2-fold, and 51 other RNAs decreased 1.5-fold.
      These RNAs encode proteins important in cell adhesion or signaling,
      transcription, RNA processing, cell-cycle regulation, and survival. Real-time RT
      PCR confirmed EBNA2-dependent expression of eight RNAs.

PMID- 16446432
TI  - Subunit-subunit interactions are critical for proton sensitivity of ROMK:
      evidence in support of an intermolecular gating mechanism.
AB  - The tetrameric K channel ROMK provides an important pathway for K secretion by
      the mammalian kidney, and the gating of this channel is highly sensitive to
      changes in cytosolic pH. Although charge-charge interactions have been implicated
      in pH sensing by this K channel tetramer, the molecular mechanism linking pH
      sensing and the gating of ion channels is poorly understood. The x-ray crystal
      structure KirBac1.1, a prokaryotic ortholog of ROMK, has suggested that channel
      gating involves intermolecular interactions of the N- and C-terminal domains of
      adjacent subunits. Here we studied channel gating behavior to changes in pH using
      giant patch clamping of Xenopus laevis oocytes expressing WT or mutant ROMK, and
      we present evidence that no single charged residue provides the pH sensor.
      Instead, we show that N-C- and C-C-terminal subunit-subunit interactions form
      salt bridges, which function to stabilize ROMK in the open state and which are
      modified by protons. We identify a highly conserved C-C-terminal arginine
      glutamate (R-E) ion pair that forms an intermolecular salt bridge and responds to
      changes in proton concentration. Our results support the intermolecular model for
      pH gating of inward rectifier K channels.

PMID- 16446433
TI  - Polyproline II conformation is one of many local conformational states and is not
      an overall conformation of unfolded peptides and proteins.
AB  - The alanine-based peptide Ac-XX(A)7OO-NH2, referred to as XAO (where X, A, and O
      denote diaminobutyric acid, alanine, and ornithine, respectively), has recently
      been proposed to possess a well defined polyproline II (P(II)) conformation at
      low temperatures. Based on the results of extensive NMR and CD investigations
      combined with theoretical calculations, reported here, we present evidence that,
      on the contrary, this peptide does not have any significant amount of organized
      P(II) structure but exists in an ensemble of conformations with a distorted bend
      in the N- and C-terminal regions. The conformational ensemble was obtained by
      molecular dynamics/simulated annealing calculations using the amber suite of
      programs with time-averaged distance and dihedral-angle restraints obtained from
      rotating-frame nuclear Overhauser effect (ROE) volumes and vicinal coupling
      constants 3J(HN Eta alpha), respectively. The computed ensemble-averaged radius
      of gyration Rg (7.4 +/- 1.0) A is in excellent agreement with that measured by
      small-angle x-ray scattering (SAXS) whereas, if the XAO peptide were in the P(II)
      conformation, Rg would be 11.6 A. Depending on the pH, peptide concentration, and
      temperature, the CD spectra of XAO do or do not possess the maximum with positive
      ellipticity in the 217-nm region, which is characteristic of the P(II) structure,
      reflecting a shifting conformational equilibrium rather than an all-or-none
      transition. The "P(II) conformation" should, therefore, be considered as one of
      the accessible conformational states of individual amino acid residues in
      peptides and proteins rather than as a structure of most of the chain in the
      early stage of folding.

PMID- 16446435
TI  - Illusory motion in Enigma: a psychophysical investigation.
AB  - Experiments to determine the optimum conditions for perceiving illusory motion in
      Engima-like patterns have also demonstrated that the illusory motion is not the
      result of unintended motion of the image on the retina due to microsaccades or
      accommodative changes in the lens of the eye but instead has a cortical origin.
      The perceived illusory activity is believed to be a consequence of neural signals
      emanating from high-contrast bars and edges in the image that emit randomly
      fluctuating signals, as expected from spiking cortical neurons. These
      fluctuations may induce illusory motion in the channels by a mechanism similar to
      that responsible for the Omega effect, in which sequences of random patterns of
      black dots presented in an annular channel produce the perception of illusory
      rotation of these dots within the annulus.

PMID- 16446434
TI  - The role of neuregulin-ErbB4 interactions on the proliferation and organization
      of cells in the subventricular zone.
AB  - Coordinated regulation of neuronal progenitor differentiation in the
      subventricular zone (SVZ) is a fundamental feature of adult neurogenesis.
      However, the molecular control of this process remains mostly undeciphered. Here,
      we investigate the role of neuregulins (NRGs) in this process and show that a NRG
      receptor, ErbB4, is primarily expressed by polysialylated neural cell adhesion
      molecule immature neuroblasts but is also detected in a subset of GFAP+
      astroglial cells, ependymal cells, and Dlx2+ precursors in the SVZ. Of the NRG
      ligands, both NRG1 and -2 are expressed by immature polysialylated neural cell
      adhesion molecule neuroblasts in the SVZ. NRG2 is also expressed by some of the
      GFAP+ putative stem cells lining the ventricles. Infusion of exogenous NRG1 leads
      to rapid aggregation of Dlx2+ cells in the SVZ and affects the initiation and
      maintenance of organized neuroblast migration from the SVZ toward the olfactory
      bulb. In contrast, the infusion of NRG2 increased the number of Sox2 and GFAP+
      precursors in the SVZ. An outcome of this NRG2 effect is an increase in the
      number of newly generated migrating neuroblasts in the rostral migratory stream
      and GABAergic interneurons in the olfactory bulb. The analysis of conditional
      null mice that lack NRG receptor, ErbB4, in the nervous system revealed that the
      observed activities of NRG2 require ErbB4 activation. These results indicate that
      different NRG ligands affect distinct populations of differentiating neural
      precursors in the neurogenic regions of the mature forebrain. Furthermore, these
      studies identify NRG2 as a factor capable of promoting SVZ proliferation, leading
      to the formation of new neurons in vivo.

PMID- 16446436
TI  - Potent diarrheagenic mechanism mediated by the cooperative action of three
      enteropathogenic Escherichia coli-injected effector proteins.
AB  - Enteropathogenic Escherichia coli (EPEC) induces a severe watery diarrhea
      responsible for several hundred thousand infant deaths each year by a process
      correlated with the loss (effacement) of absorptive microvilli. Effacement is
      linked to the locus of enterocyte effacement pathogenicity island that encodes an
      "injection system," "effector" proteins, and the Intimin outer membrane protein.
      Here, we reveal that effacement (i) is a two-step process, (ii) requires the
      cooperative action of three injected effectors (Map, EspF, and Tir) as well as
      Intimin, and (iii) leads to the retention, not release (into the extracellular
      milieu), of the detached microvillar material. We also discover that EPEC rapidly
      inactivates the sodium-d-glucose cotransporter (SGLT-1) by multiple mechanisms.
      Indeed, the finding that one mechanism occurs more rapidly than microvilli
      effacement provides a plausible explanation for the rapid onset of severe watery
      diarrhea, given the crucial role of SGLT-1 in the daily uptake of approximately 6
      liters of fluids from the normal intestine. The importance of SGLT-1 in the
      disease process is supported by severe EPEC diarrheal cases being refractory to
      oral rehydration therapy (dependent on SGLT-1 function). Moreover, the
      identification of effector activities that alter microvilli structure and SGLT-1
      function provides new tools for studying the underlying regulatory processes.

PMID- 16446437
TI  - Abeta and tau form soluble complexes that may promote self aggregation of both
      into the insoluble forms observed in Alzheimer's disease.
AB  - To date, there is no reasonable explanation as to why plaques and tangles
      simultaneously accumulate in Alzheimer's disease (AD). We demonstrate here by
      Western blotting and ELISA that a stable complex can form between tau and amyloid
      beta protein (Abeta). This complex enhances tau phosphorylation by GSK3beta, but
      the phosphorylation then promotes dissociation of the complex. We have localized
      the sites of this interaction by using peptide membrane arrays. Abeta binds to
      multiple tau peptides, especially those in exons 7 and 9. This binding is sharply
      reduced or abolished by phosphorylation of specific serine and threonine
      residues. Conversely, tau binds to multiple Abeta peptides in the mid to C
      terminal regions of Abeta. This binding is also significantly decreased by
      GSK3beta phosphorylation of tau. We used surface plasmon resonance to determine
      the binding affinity of Abeta for tau and found it to be in the low nanomolar
      range and almost 1,000-fold higher than tau for itself. In soluble extracts from
      AD and control brain tissue, we detected Abeta bound to tau in ELISAs. We also
      found by double immunostaining of AD brain tissue that phosphorylated tau and
      Abeta form separate insoluble complexes within the same neurons and their
      processes. We hypothesize that in AD, an initial step in the pathogenesis may be
      the intracellular binding of soluble Abeta to soluble nonphosphorylated tau, thus
      promoting tau phosphorylation and Abeta nucleation. Blocking the sites where
      Abeta initially binds to tau might arrest the simultaneous formation of plaques
      and tangles in AD.

PMID- 16446438
TI  - Nod1-dependent control of tumor growth.
AB  - Nod1, a cytosolic protein that senses meso-diaminopimelic acid-containing ligands
      derived from peptidoglycan, plays a role in host responses to invasive bacteria.
      Here we describe a function for Nod1, whereby it controls tumor formation. Cell
      lines derived from the human breast cancer epithelial cell line MCF-7 were used
      in a severe combined immune deficiency (SCID) mouse xenograft model to
      characterize a pathway linking Nod1 to the growth of estrogen-sensitive tumors.
      In MCF-7 cells, the absence of Nod1 correlates with tumor growth, an increased
      sensitivity to estrogen-induced cell proliferation, and a failure to undergo Nod1
      dependent apoptosis. Conversely, overexpression of Nod1 in MCF-7 cells results in
      inhibition of estrogen-dependent tumor growth and reduction of estrogen-induced
      proliferative responses in vitro.

PMID- 16446440
TI  - Profile of George Oster.

PMID- 16446441
TI  - Imaging hair cell transduction at the speed of sound: dynamic behavior of
      mammalian stereocilia.
AB  - The cochlea contains two types of sensory cells, the inner and outer hair cells.
      Sound-evoked deflection of outer hair cell stereocilia leads to fast force
      production that will enhance auditory sensitivity up to 1,000-fold. In contrast,
      inner hair cells are thought to have a purely receptive function. Deflection of
      their stereocilia produces receptor potentials, transmitter release, and action
      potentials in the auditory nerve. Here, we describe a method for rapid confocal
      imaging. The method was used to image stereocilia during simultaneous sound
      stimulation in an in vitro preparation of the guinea pig cochlea. We show that
      inner hair cell stereocilia move because they interact with the fluid surrounding
      the hair bundles, but stereocilia deflection occurs at a different phase of the
      stimulus than is generally expected. In outer hair cells, stereocilia deflections
      were approximately 1/3 of the reticular lamina displacement. Smaller deflections
      were found in inner hair cells. The ratio between stereocilia deflection and
      reticular lamina displacement is important for auditory function, because it
      determines the stimulus applied to transduction channels. The low ratio measured
      here suggests that amplification of hair-bundle movements may be necessary in
      vivo to preserve transduction fidelity at low stimulus levels. In the case of the
      inner hair cells, this finding would represent a departure from traditional views
      on their function.

PMID- 16446439
TI  - Atomic structure and nonhomologous end-joining function of the polymerase
      component of bacterial DNA ligase D.
AB  - DNA ligase D (LigD) is a large polyfunctional protein that participates in a
      recently discovered pathway of nonhomologous end-joining in bacteria. LigD
      consists of an ATP-dependent ligase domain fused to a polymerase domain (Pol) and
      a phosphoesterase module. The Pol activity is remarkable for its dependence on
      manganese, its ability to perform templated and nontemplated primer extension
      reactions, and its preference for adding ribonucleotides to blunt DNA ends. Here
      we report the 1.5-A crystal structure of the Pol domain of Pseudomonas LigD and
      its complexes with manganese and ATP/dATP substrates, which reveal a minimized
      polymerase with a two-metal mechanism and a fold similar to that of archaeal DNA
      primase. Mutational analysis highlights the functionally relevant atomic contacts
      in the active site. Although distinct nucleoside conformations and contacts for
      ATP versus dATP are observed in the cocrystals, the functional analysis suggests
      that the ATP-binding mode is the productive conformation for dNMP and rNMP
      incorporation. We find that a mutation of Mycobacterium LigD that uniquely
      ablates the polymerase activity results in increased fidelity of blunt-end double
      strand break repair in vivo by virtue of eliminating nucleotide insertions at the
      recombination junctions. Thus, LigD Pol is a direct catalyst of mutagenic
      nonhomologous end-joining in vivo. Our studies underscore a previously
      uncharacterized role for the primase-like polymerase family in DNA repair.

PMID- 16446442
TI  - Suppression of gross chromosomal rearrangements by yKu70-yKu80 heterodimer
      through DNA damage checkpoints.
AB  - The inactivation of either subunit of the Ku70-Ku80 heterodimer, which functions
      in nonhomologous end-joining and telomere maintenance, generates severe defects
      such as sensitivity to DNA damage, telomere shortening, and increased gross
      chromosomal rearrangements (GCRs) that are frequently observed in many cancers.
      To understand the mechanism of Ku as a genome gatekeeper, we overexpressed the
      yKu70-yKu80 heterodimer and monitored the formation of GCRs. Ku overexpression
      suppressed the formation of either spontaneously generated GCRs or those induced
      by treatments with different DNA damaging agents. Interestingly, this suppression
      depended on Ku's interaction with DNA damage checkpoints and not through
      nonhomologous end-joining. We also demonstrate that the inactivation of
      telomerase inhibitor, Pif1 along with Ku overexpression or the overexpression of
      Pif1 in either yku70 or yku80 strains arrested the cell cycle at S phase in a DNA
      damage checkpoint-dependent fashion. Lastly, Ku overexpression causes cell growth
      delay, which depends on intact Rad27. In summary, the results presented here
      suggest that Ku functions as a genomic gatekeeper through its crosstalk with DNA
      damage checkpoints.

PMID- 16446443
TI  - Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma
      cruzi proline racemase.
AB  - Amino acid racemases catalyze the stereoinversion of the chiral C alpha to
      produce the d-enantiomers that participate in biological processes, such as cell
      wall construction in prokaryotes. Within this large protein family, bacterial
      proline racemases have been extensively studied as a model of enzymes acting with
      a pyridoxal-phosphate-independent mechanism. Here we report the crystal structure
      of the proline racemase from the human parasite Trypanosoma cruzi (TcPRACA), a
      secreted enzyme that triggers host B cell polyclonal activation, which prevents
      specific humoral immune responses and is crucial for parasite evasion and fate.
      The enzyme is a homodimer, with each monomer folded in two symmetric alpha/beta
      subunits separated by a deep crevice. The structure of TcPRACA in complex with a
      transition-state analog, pyrrole-2-carboxylic acid, reveals the presence of one
      reaction center per monomer, with two Cys residues optimally located to perform
      acid/base catalysis through a carbanion stabilization mechanism. Mutation of the
      catalytic Cys residues abolishes the enzymatic activity but preserves the
      mitogenic properties of the protein. In contrast, inhibitor binding promotes the
      closure of the interdomain crevice and completely abrogates B cell proliferation,
      suggesting that the mitogenic properties of TcPRACA depend on the exposure of
      transient epitopes in the ligand-free enzyme.

PMID- 16446445
TI  - First molecular and biochemical analysis of in vivo affinity maturation in an
      ectothermic vertebrate.
AB  - The cartilaginous fish are the oldest phylogenetic group in which Igs have been
      found. Sharks produce a unique Ig isotype, IgNAR, a heavy-chain homodimer that
      does not associate with light chains. Instead, the variable (V) regions of IgNAR
      bind antigen as soluble single domains. Our group has shown that IgNAR plays an
      integral part in the humoral response of nurse sharks (Ginglymostoma cirratum)
      upon antigen challenge. Here, we generated phage-displayed libraries of IgNAR V
      regions from an immunized animal and found a family of clones derived from the
      same rearrangement event but differentially mutated during expansion. Because of
      the cluster organization of shark Ig genes and the paucicopy nature of IgNAR, we
      were able to construct the putative ancestor of this family. By studying
      mutations in the context of clone affinities, we found evidence that affinity
      maturation occurs for this isotype. Subsequently, we were able to identify
      mutations important in the affinity improvement of this family. Because the
      family clones were all obtained after immunization, they provide insight into the
      in vivo maturation mechanisms, in general, and for single-domain antibody
      fragments.

PMID- 16446444
TI  - Chlamydia trachomatis polymorphic membrane protein D is a species-common pan
      neutralizing antigen.
AB  - Infections caused by the obligate intracellular pathogen Chlamydia trachomatis
      have a marked impact on human health. C. trachomatis serovariants are the leading
      cause of bacterial sexually transmitted disease and infectious preventable
      blindness. Despite decades of effort, there is no practical vaccine against C.
      trachomatis diseases. Here we report that all C. trachomatis reference serotypes
      responsible for sexually transmitted disease and blinding trachoma synthesize a
      highly conserved surface-exposed antigen termed polymorphic membrane protein D
      (PmpD). We show that Ab specific to PmpD are neutralizing in vitro. We also
      present evidence that Ab against serovariable-neutralizing targets, such as the
      major outer membrane protein, block PmpD neutralization. This finding suggests
      that a decoy-like immune evasion strategy may be active in vivo whereby
      immunodominant type-specific surface antigens block the neutralizing ability of
      species-common PmpD Ab. Collectively, these results show that PmpD is a
      previously uncharacterized C. trachomatis species-common pan-neutralizing target.
      Moreover, a vaccine protocol using recombinant PmpD to elicit neutralizing Ab in
      the absence of immunodominant type-specific Ab might be highly efficacious and
      surpass the level of protection achieved through natural immunity.

PMID- 16446446
TI  - Insight into autoproteolytic activation from the structure of cephalosporin
      acylase: a protein with two proteolytic chemistries.
AB  - Cephalosporin acylase (CA), a member of the N-terminal nucleophile hydrolase
      family, is activated through sequential primary and secondary autoproteolytic
      reactions with the release of a pro segment. We have determined crystal
      structures of four CA mutants. Two mutants are trapped after the primary
      cleavage, and the other two undergo secondary cleavage slowly. These structures
      provide a look at pro-segment conformation during activation in N-terminal
      nucleophile hydrolases. The highly strained helical pro segment of precursor is
      transformed into a relaxed loop in the intermediates, suggesting that the
      relaxation of structural constraints drives the primary cleavage reaction. The
      secondary autoproteolytic step has been proposed to be intermolecular. However,
      our analysis provides evidence that CA is processed in two sequential steps of
      intramolecular autoproteolysis involving two distinct residues in the active
      site, the first a serine and the second a glutamate.

PMID- 16446447
TI  - Interaction of MEQ protein and C-terminal-binding protein is critical for
      induction of lymphomas by Marek's disease virus.
AB  - Marek's disease virus (MDV) is an oncogenic herpesvirus that induces fatal T cell
      lymphomas in chickens. With more than 20 billion doses of vaccine used annually,
      vaccination constitutes the cornerstone of Marek's disease control. Despite the
      success of vaccination, evolution of virulence among MDV strains continues to
      threaten the effectiveness of the current Marek's disease vaccines. MDV-encoded
      protein MEQ (MDV EcoRI Q) probably acts as a transcription factor and is
      considered to be the major MDV oncoprotein. MEQ sequence shows a Pro-Leu-Asp-Leu
      Ser (PLDLS) motif known to bind C-terminal-binding protein (CtBP), a highly
      conserved cellular transcriptional corepressor with roles in the regulation of
      development, proliferation, and apoptosis. Here we show that MEQ can physically
      and functionally interact with CtBP through this motif and that this interaction
      is critical for oncogenesis because mutations in the CtBP-interaction domain
      completely abolished oncogenicity. This direct role for MEQ-CtBP interaction in
      MDV oncogenicity highlights the convergent evolution of molecular mechanisms of
      neoplastic transformation by herpesviruses because Epstein-Barr virus
      oncoproteins EBNA 3A and 3C also interact with CtBP. We also demonstrate that the
      nononcogenic MDV generated by mutagenesis of the CtBP-interaction domain of MEQ
      has the potential to be an improved vaccine against virulent MDV infection.
      Engineering MDV with precisely defined attenuating mutations, therefore,
      represents an effective strategy for generating new vaccines against this major
      poultry disease.

PMID- 16446448
TI  - The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase.
AB  - Endogenously formed reactive oxygen species continuously damage cellular
      constituents including DNA. These challenges, coupled with exogenous exposure to
      agents that generate reactive oxygen species, are both associated with normal
      aging processes and linked to cardiovascular disease, cancer, cataract formation,
      and fatty liver disease. Although not all of these diseases have been
      definitively shown to originate from mutations in nuclear DNA or mitochondrial
      DNA, repair of oxidized, saturated, and ring-fragmented bases via the base
      excision repair pathway is known to be critical for maintaining genomic
      stability. One enzyme that initiates base excision repair of ring-fragmented
      purines and some saturated pyrimidines is NEIL1, a mammalian homolog to
      Escherichia coli endonuclease VIII. To investigate the organismal consequences of
      a deficiency in NEIL1, a knockout mouse model was created. In the absence of
      exogenous oxidative stress, neil1 knockout (neil1-/-) and heterozygotic (neil1+/
      ) mice develop severe obesity, dyslipidemia, and fatty liver disease and also
      have a tendency to develop hyperinsulinemia. In humans, this combination of
      clinical manifestations, including hypertension, is known as the metabolic
      syndrome and is estimated to affect >40 million people in the United States.
      Additionally, mitochondrial DNA from neil1-/- mice show increased levels of
      steady-state DNA damage and deletions relative to wild-type controls. These data
      suggest an important role for NEIL1 in the prevention of the diseases associated
      with the metabolic syndrome.

PMID- 16446449
TI  - Determination of the geometric structure of the metal site in a blue copper
      protein by paramagnetic NMR.
AB  - The biological function of metalloproteins is closely tied to the geometric and
      electronic structures of the metal sites. Here, we show that the geometric
      structure of the metal site of a metalloprotein in solution can be determined
      from experimentally measured electron-nuclear spin-spin interactions obtained by
      NMR. Thus, the geometric metal site structure of plastocyanin from Anabaena
      variabilis was determined by including the paramagnetic relaxation enhancement of
      protons close to the copper site as restraints in a conventional NMR structure
      determination, together with the distribution of the unpaired electron onto the
      ligand atoms. Also, the interproton distances (nuclear Overhauser enhancements)
      and dihedral angles (scalar nuclear spin-spin couplings) normally used in NMR
      structure determinations were included as restraints. The structure calculations
      were carried out with the program X-PLOR and a module that takes into account the
      specific characteristics of the paramagnetic restraints. A well defined metal
      site structure was obtained with the structural characteristics of the blue
      copper site, including a distorted tetrahedral geometry, a short Cu-Cys S gamma
      bond, and a long Cu-Met S delta bond. Overall, the agreement of the obtained
      metal site structure of Anabaena variabilis plastocyanin with those of other
      plastocyanins obtained by x-ray crystallography confirms the reliability of the
      approach.

PMID- 16446450
TI  - Weighting of experimental evidence in macromolecular structure determination.
AB  - The determination of macromolecular structures requires weighting of experimental
      evidence relative to prior physical information. Although it can critically
      affect the quality of the calculated structures, experimental data are routinely
      weighted on an empirical basis. At present, cross-validation is the most rigorous
      method to determine the best weight. We describe a general method to adaptively
      weight experimental data in the course of structure calculation. It is further
      shown that the necessity to define weights for the data can be completely
      alleviated. We demonstrate the method on a structure calculation from NMR data
      and find that the resulting structures are optimal in terms of accuracy and
      structural quality. Our method is devoid of the bias imposed by an empirical
      choice of the weight and has some advantages over estimating the weight by cross
      validation.

PMID- 16446451
TI  - In vivo imaging of juxtaglomerular neuron turnover in the mouse olfactory bulb.
AB  - As a consequence of adult neurogenesis, the olfactory bulb (OB) receives a
      continuous influx of newborn neurons well into adulthood. However, their rates of
      generation and turnover, the factors controlling their survival, and how newborn
      neurons intercalate into adult circuits are largely unknown. To visualize the
      dynamics of adult neurogenesis, we produced a line of transgenic mice expressing
      GFP in approximately 70% of juxtaglomerular neurons (JGNs), a population that
      undergoes adult neurogenesis. Using in vivo two-photon microscopy, time-lapse
      analysis of identified JGN cell bodies revealed a neuronal turnover rate of
      approximately 3% of this population per month. Although new neurons appeared and
      older ones disappeared, the overall number of JGNs remained constant. This
      approach provides a dynamic view of the actual appearance and disappearance of
      newborn neurons in the vertebrate central nervous system, and provides an
      experimental substrate for functional analysis of adult neurogenesis.

PMID- 16446452
TI  - A method for determining the dependence of calcium oscillations on inositol
      trisphosphate oscillations.
AB  - In some cell types, oscillations in the concentration of free intracellular
      calcium ([Ca2+]) are accompanied by oscillations in the concentration of inositol
      1,4,5-trisphosphate ([IP3]). However, in most cell types it is still an open
      question as to whether oscillations in [IP3] are necessary for Ca2+ oscillations
      in vivo, or whether they merely follow passively. Using a wide range of models,
      we show that the response to an artificially applied pulse of IP3 can be used to
      distinguish between these two cases. Hence, we show that muscarinic receptor
      mediated, long-period Ca2+ oscillations in pancreatic acinar cells depend on
      [IP3] oscillations, whereas short-period Ca2+ oscillations in airway smooth
      muscle do not.

PMID- 16446454
TI  - F-box-like domain in the polerovirus protein P0 is required for silencing
      suppressor function.
AB  - Plants employ small RNA-mediated posttranscriptional gene silencing as a virus
      defense mechanism. In response, plant viruses encode proteins that can suppress
      RNA silencing, but the mode of action of most such proteins is poorly understood.
      Here, we show that the silencing suppressor protein P0 of two Arabidopsis
      infecting poleroviruses interacts by means of a conserved minimal F-box motif
      with Arabidopsis thaliana orthologs of S-phase kinase-related protein 1 (SKP1), a
      component of the SCF family of ubiquitin E3 ligases. Point mutations in the F-box
      like motif abolished the P0-SKP1 ortholog interaction, diminished virus
      pathogenicity, and inhibited the silencing suppressor activity of P0. Knockdown
      of expression of a SKP1 ortholog in Nicotiana benthamiana rendered the plants
      resistant to polerovirus infection. Together, the results support a model in
      which P0 acts as an F-box protein that targets an essential component of the host
      posttranscriptional gene silencing machinery.

PMID- 16446453
TI  - Selection of biocatalysts for chemical synthesis.
AB  - To determine whether microbial chemosensors can be used to find new or better
      biocatalysts, we constructed Escherichia coli hosts that recognize the product of
      a biocatalytic conversion through the transcriptional activator NahR and respond
      by expression of a lacZ or tetA reporter gene. Equipped with a benzaldehyde
      dehydrogenase (XylC from Pseudomonas putida), the lacZ-based host responded to
      the oxidation of benzaldehyde and 2-hydroxybenzaldehyde to the corresponding
      benzoic acids by forming blue colonies, whereas XylC- cells did not. Similarly,
      the tetA-based host was able to grow under selective conditions only when
      equipped with XylC, enabling selection of biocatalytically active cells in
      inactive populations at frequencies as low as 10(-6).

PMID- 16446455
TI  - Odorant responses of olfactory sensory neurons expressing the odorant receptor
      MOR23: a patch clamp analysis in gene-targeted mice.
AB  - A glomerulus in the mammalian olfactory bulb receives axonal inputs from
      olfactory sensory neurons (OSNs) that express the same odorant receptor (OR).
      Glomeruli are generally thought to represent functional units of olfactory
      coding, but there are no data on the electrophysiological properties of OSNs that
      express the same endogenous OR. Here, using patch clamp recordings in an intact
      epithelial preparation, we directly measured the transduction currents and
      receptor potentials from the dendritic knobs of mouse OSNs that express the
      odorant receptor MOR23 along with the green fluorescent protein. All of the 53
      cells examined responded to lyral, a known ligand for MOR23. There were profound
      differences in response kinetics, particularly in the deactivation phase. The
      cells were very sensitive to lyral, with some cells responding to as little as 10
      nM. The dynamic range was unexpectedly broad, with threshold and saturation in
      individual cells often covering three log units of lyral concentration. The
      potential causes and biological significance of this cellular heterogeneity are
      discussed. Patch clamp recording from OSNs that express a defined OR provides a
      powerful approach to investigate the sensory inputs to individual glomeruli.

PMID- 16446456
TI  - A fast response mechanism for insulin storage in crystals may involve kink
      generation by association of 2D clusters.
AB  - Crystals that are likely rhombohedral of Zn-insulin hexamers form in the islets
      of Langerhans in the pancreases of many mammals. The suggested functions of
      crystal formation is to protect the insulin from proteases and increase the
      degree of conversion of soluble proinsulin. To accomplish these ends, crystal
      growth should be fast and adaptable to rate fluctuations in the conversion
      reaction. Zn-insulin crystals grow layer by layer. Each layer spreads by the
      attachment of molecules to kinks located at the layers' edges, also called steps.
      The kinks are thought to be generated either by thermal fluctuations, as
      postulated by Gibbs, or by 1D nucleation of new crystalline rows. The kink
      density determines the rate at which steps advance, and these two kink-generation
      mechanisms lead to weak near-linear responses of the growth rate to concentration
      variations. We demonstrate for the crystallization of Zn-insulin a mechanism of
      kink generation whereby 2D clusters of several insulin molecules preformed on the
      terraces between steps associate to the steps. This mechanism results in several
      fold-higher kink density, a faster rate of crystallization, and a high
      sensitivity of the kinetics to small increases of the solute concentration. If
      the found mechanism operates during insulin crystallization in vivo, it could be
      a part of the biological regulation of insulin production and function. For other
      crystallizing materials in biological and nonbiological systems, this mechanism
      provides an understanding of the often seen nonlinear acceleration of the
      kinetics.

PMID- 16446457
TI  - Abscisic acid-dependent multisite phosphorylation regulates the activity of a
      transcription activator AREB1.
AB  - bZIP-type transcription factors AREBs/ABFs bind an abscisic acid (ABA)-responsive
      cis-acting element named ABRE and transactivate downstream gene expression in
      Arabidopsis. Because AREB1 overexpression could not induce downstream gene
      expression, activation of AREB1 requires ABA-dependent posttranscriptional
      modification. We confirmed that ABA activated 42-kDa kinase activity, which, in
      turn, phosphorylated Ser/Thr residues of R-X-X-S/T sites in the conserved regions
      of AREB1. Amino acid substitutions of R-X-X-S/T sites to Ala suppressed
      transactivation activity, and multiple substitution of these sites resulted in
      almost complete suppression of transactivation activity in transient assays. In
      contrast, substitution of the Ser/Thr residues to Asp resulted in high
      transactivation activity without exogenous ABA application. A phosphorylated,
      transcriptionally active form was achieved by substitution of Ser/Thr in all
      conserved R-X-X-S/T sites to Asp. Transgenic plants overexpressing the
      phosphorylated active form of AREB1 expressed many ABA-inducible genes, such as
      RD29B, without ABA treatment. These results indicate that the ABA-dependent
      multisite phosphorylation of AREB1 regulates its own activation in plants.

PMID- 16446458
TI  - Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical
      properties of cells.
AB  - We show that actin filaments, shortened to physiological lengths by gelsolin and
      cross-linked with recombinant human filamins (FLNs), exhibit dynamic elastic
      properties similar to those reported for live cells. To achieve elasticity values
      of comparable magnitude to those of cells, the in vitro network must be subjected
      to external prestress, which directly controls network elasticity. A molecular
      requirement for the strain-related behavior at physiological conditions is a
      flexible hinge found in FLNa and some FLNb molecules. Basic physical properties
      of the in vitro filamin-F-actin network replicate the essential mechanical
      properties of living cells. This physical behavior could accommodate passive
      deformation and internal organelle trafficking at low strains yet resist
      externally or internally generated high shear forces.

PMID- 16446461
TI  - Legislating prevention.

PMID- 16446460
TI  - Chemosensing in Escherichia coli: two regimes of two-state receptors.
AB  - The chemotaxis network in Escherichia coli is remarkable for its sensitivity to
      small relative changes in the concentrations of multiple chemical signals. We
      present a model for signal integration by mixed clusters of interacting two-state
      chemoreceptors. Our model results compare favorably to the results obtained by
      Sourjik and Berg with in vivo fluorescence resonance energy transfer.
      Importantly, we identify two distinct regimes of behavior, depending on the
      relative energies of the two states of the receptors. In regime I, coupling of
      receptors leads to high sensitivity, while in regime II, coupling of receptors
      leads to high cooperativity, i.e., high Hill coefficient. For homogeneous
      receptors, we predict an observable transition between regime I and regime II
      with increasing receptor methylation or amidation.

PMID- 16446462
TI  - Dire need for medical officers of health.

PMID- 16446459
TI  - Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency.
AB  - Age-related accumulation of cellular damage and death has been linked to
      oxidative stress. Calorie restriction (CR) is the most robust, nongenetic
      intervention that increases lifespan and reduces the rate of aging in a variety
      of species. Mechanisms responsible for the antiaging effects of CR remain
      uncertain, but reduction of oxidative stress within mitochondria remains a major
      focus of research. CR is hypothesized to decrease mitochondrial electron flow and
      proton leaks to attenuate damage caused by reactive oxygen species. We have
      focused our research on a related, but different, antiaging mechanism of CR.
      Specifically, using both in vivo and in vitro analyses, we report that CR reduces
      oxidative stress at the same time that it stimulates the proliferation of
      mitochondria through a peroxisome proliferation-activated receptor coactivator 1
      alpha signaling pathway. Moreover, mitochondria under CR conditions show less
      oxygen consumption, reduce membrane potential, and generate less reactive oxygen
      species than controls, but remarkably they are able to maintain their critical
      ATP production. In effect, CR can induce a peroxisome proliferation-activated
      receptor coactivator 1 alpha-dependent increase in mitochondria capable of
      efficient and balanced bioenergetics to reduce oxidative stress and attenuate age
      dependent endogenous oxidative damage.

PMID- 16446463
TI  - Provinces lure physicians from one another.

PMID- 16446465
TI  - Wait-time benchmarks fall short.

PMID- 16446467
TI  - A broader context for maternal mortality.

PMID- 16446468
TI  - The role of the Coombs test in evaluating hemolysis in adults.

PMID- 16446469
TI  - Is waist-to-hip ratio a better marker of cardiovascular risk than body mass
      index?

PMID- 16446470
TI  - A smouldering epidemic.

PMID- 16446471
TI  - An elderly man with sudden-onset shortness of breath and hydropneumothorax.

PMID- 16446472
TI  - Prevalence of lower-extremity amputation among patients with diabetes mellitus:
      is height a factor?
AB  - BACKGROUND: Taller diabetic patients are at higher risk of peripheral sensory
      loss than shorter diabetic patients and thus may be at increased risk of lower
      extremity ulcers and amputation. In a large telephone survey, the prevalence of
      lower-extremity amputation among patients with diabetes mellitus was determined
      and the association between height and lower-extremity amputation evaluated.
      METHODS: Of 256,036 patients identified from hospital and clinic databases who
      had a diagnosis of diabetes and were seen at those institutions between 1995 and
      1998, 128,572 were randomly selected to be interviewed by telephone between 1995
      and 2002. Of the 93,484 patients who agreed to be interviewed, 386 were excluded
      (age < 18 years); this left 93,116 diabetec patients (42,970 men and 50,146
      women) for inclusion in the study. RESULTS: Of the 93,116 patients interviewed,
      3259 (3.5%) had type 1 diabetes. Lower-extremity amputation was performed in 1.7%
      and 0.8% of the patients with type 1 and type 2 diabetes, respectively. The
      prevalence of amputation did not differ significantly between men and women with
      type 1 diabetes but was significantly higher among men than among women with type
      2 diabetes (0.9% v. 0.7%). Height (every 10-cm increment) was significantly
      associated with lower-extremity amputation (adjusted odds ratio [OR] 1.16, 95%
      confidence interval [CI] 1.03-1.32). In a subgroup of 9295 patients for whom data
      on fasting plasma glucose levels and dyslipidemia were available, and after
      additional adjustment for these 2 variables, body height remained an independent
      predictor of lower-extremity amputation (adjusted OR for every 10 cm of height
      1.79, 95% CI 1.14-2.82). INTERPRETATION: Height is an independent predictor of
      lower-extremity amputation among patients with type 1 and type 2 diabetes
      mellitus.

PMID- 16446473
TI  - Utilization and outcomes of HbA1c testing: a population-based study.

PMID- 16446474
TI  - The Canadian Diabetes Association guidelines: putting the evidence first.

PMID- 16446476
TI  - On bias and transparency in the development of influential recommendations.

PMID- 16446477
TI  - Assessing and scaling the knowledge pyramid: the good-guideline guide.

PMID- 16446480
TI  - Determining optimal catheterization rates.

PMID- 16446481
TI  - Treponema pallidum macrolide resistance in BC.

PMID- 16446482
TI  - Measuring frailty in geriatric patients.

PMID- 16446483
TI  - Ethics and investment funds.

PMID- 16446478
TI  - Epigenetics and human disease: translating basic biology into clinical
      applications.
AB  - Epigenetics refers to the study of heritable changes in gene expression that
      occur without a change in DNA sequence. Research has shown that epigenetic
      mechanisms provide an "extra" layer of transcriptional control that regulates how
      genes are expressed. These mechanisms are critical components in the normal
      development and growth of cells. Epigenetic abnormalities have been found to be
      causative factors in cancer, genetic disorders and pediatric syndromes as well as
      contributing factors in autoimmune diseases and aging. In this review, we examine
      the basic principles of epigenetic mechanisms and their contribution to human
      health as well as the clinical consequences of epigenetic errors. In addition, we
      address the use of epigenetic pathways in new approaches to diagnosis and
      targeted treatments across the clinical spectrum.

PMID- 16446484
TI  - Ethics and investment funds.

PMID- 16446485
TI  - Controlled-release opioids and alcohol.

PMID- 16446487
TI  - Targeting apoptosis with dietary bioactive agents.
AB  - Apoptosis, a form of programmed cell death, is a pivotal defense against the
      occurrence of cancer and is essential to metazoans in maintaining tissue
      homeostasis. Apoptosis exhibits a distinctive phenotype and involves elimination
      of potentially deleterious cells. Many diseases have been associated with
      aberrantly regulated apoptotic cell death, ultimately leading to inhibition of
      apoptosis and propagation of diseases such as cancer. Elucidation of the critical
      events associated with carcinogenesis provides the opportunity for dietary
      intervention to prevent cancer development through induction of apoptosis,
      particularly by bioactive agents or functional foods. Diet is a significant
      environmental factor in the overall cancer process and can exacerbate or
      interfere with carcinogenesis. Apoptosis occurs primarily through two well
      recognized pathways in cells, including the intrinsic, or mitochondrial-mediated,
      effector mechanism and the extrinsic, or death receptor-mediated, effector
      mechanism. In addition to diet's effects on protein expression and function,
      evidence is also accumulating that a large number of dietary food components can
      exert effects on the human genome, either directly or indirectly, to modulate
      gene expression. In fact, many diet-related genes are involved in carcinogenesis
      as well as apoptosis, and thus are ultimately molecular targets for dietary
      chemoprevention. There are multiple steps within pathways in which dietary
      components can alter gene expression and phenotypes of cells and thus influence
      cancer outcomes (nutritional transcriptomic effect). Thus, apoptosis is an
      emerging therapeutic target of bioactive agents of diet. In this review, the
      process of apoptosis is discussed and the potential mechanistic interaction of
      bioactive agents, as components of functional foods, is explored within the
      context of apoptosis.

PMID- 16446488
TI  - Gastrointestinal inflammation: a central component of mucosal defense and repair.
AB  - The mucosal layer of the gastrointestinal (GI) tract is able to resist digestion
      by the endogenous substances that we secrete to digest foodstuffs. So-called
      "mucosal defense" is multi-factorial and can be modulated by a wide range of
      substances, many of which are classically regarded as inflammatory mediators.
      Damage to the GI mucosa, and its subsequent repair, are also modulated by various
      inflammatory mediators. In this article, we provide a review of some of the key
      inflammatory mediators that modulate GI mucosal defense, injury, and repair.
      Among the mediators discussed are nitric oxide, polyamines, the eicosanoids
      (prostaglandins and lipoxins), protease-activated receptors, and cytokines. Many
      of these endogenous factors, or the enzymes involved in their synthesis, are
      considered potential therapeutic targets for the treatment of diseases of the
      digestive tract that are characterized by inflammation and ulceration.

PMID- 16446489
TI  - Metallothionein and liver cell regeneration.
AB  - Hepatocytes in adults are in a nonproliferative state but they have high capacity
      to regenerate within few hours after an injury. After partial hepatectomy or
      chemical injury, hepatocytes undergo a synchronized multistep process consisting
      of priming/initiation, proliferation, and termination. These distinct steps are
      essential for restoring the structure and functions of liver. The mechanisms
      involved in each of these steps of regeneration are well documented from various
      laboratories and are described in several reviews. We briefly describe these
      steps and the involvement of various cytokines and growth factors for cell
      regeneration in this short review. Liver cell regeneration may also involve stem
      cell proliferation. The regenerating cells require large amounts of zinc within a
      short time, and this requirement is met by induction of a zinc and copper binding
      protein, metallothionein (MT), during the priming step, soon after an injury.
      There are several reports on the transfer of zinc from MT to various
      metalloenzymes and transcription factors. Genetically modified mouse models have
      been used to study the involvement of interleukin (IL)-6 and tumor necrosis
      factor (TNF)-alpha in cell regeneration. The use of an MT-knockout mouse has
      enabled us to investigate the specific role of MT in liver regeneration after
      partial hepatectomy, chemical injury, and fibrosis. Several studies have
      suggested a defective liver regeneration after an injury in MT-knockout mice.
      There is cumulative evidence that indicates an essential role for MT in liver
      cell regeneration.

PMID- 16446490
TI  - Store-operated Ca2+ channel in renal microcirculation and glomeruli.
AB  - Store-operated Ca2+ channel (SOC) is defined as a channel that opens in response
      to depletion of the internal Ca2+ stores. During the last decade, many
      investigators have made a great effort to identify and characterize SOC, and to
      evaluate its physiologic function and pathophysiologic relevance in a variety of
      cell lines, primary cultures, and native tissues. To date, accumulating evidence
      has demonstrated that SOC is an essential Ca2+ entry mechanism in vascular smooth
      muscle cells of renal microvasculature and glomerular mesangial cells, both of
      which tightly control glomerular hemodynamics and filtration. Store-operated
      Ca2+, combined with other types of Ca2+ entry channels, constitutes a profile of
      Ca2+ changes in response to physiologic vasoconstrictors and, thereby, regulates
      renal microcirculation and mesangial function. In addition, SOC is associated
      with altered Ca2+ signaling occurring in diseased kidneys, such as diabetic
      nephropathy. Although the gating mechanism and molecular identity of SOC are
      still enigmatic and may be cell-type and tissue specific, data from several
      independent groups suggest that protein kinase C plays an important role in SOC
      activation and that certain isoforms of canonical transient receptor potential
      (TRPC) proteins are candidates of SOC in renal microvessels and mesangial cells.

PMID- 16446492
TI  - Fourier transform infrared spectroscopic analysis of the intact zona pellucida of
      the mammalian egg: changes in the secondary structure of bovine zona pellucida
      proteins during fertilization.
AB  - The zona pellucida is the acellular transparent envelope surrounding the
      mammalian oocyte. An analysis of the changes in the structures of zona pellucida
      proteins is essential for understanding the molecular mechanisms underlying the
      important physiological roles of the zona during fertilization and
      preimplantation. The hardening of the zona caused by the structural changes
      during fertilization is generally accepted to be responsible for blocking
      polyspermy. In this study, we analyzed changes in the secondary structure of the
      zona during fertilization by Fourier transform infrared (FTIR) spectroscopy and
      transmission electron microscopy. The predominance of beta-sheet structure in
      porcine ovarian egg zona proteins in water was ascertained using FTIR spectra.
      Alpha-helix structure was also present. The attenuated total reflection (ATR)
      FTIR spectrum of intact, unsolubilized porcine zonae pellucidae from ovarian eggs
      indicated that the zona proteins in the native zona pellucida also have beta
      structure as the main constituent. Attenuated total reflection-FTIR spectroscopy
      of intact bovine zona pellucida obtained from ovarian and fertilized eggs at the
      blastocyst stage revealed that the beta-structure content increased during
      fertilization. Furthermore, a reduction of the thickness of the zona during
      fertilization was observed using transmission electron microscopy. Therefore, the
      change in the zona architecture that causes hardening of the zona during
      fertilization is accompanied by changes in the secondary structure of the zona
      proteins.

PMID- 16446491
TI  - eNOS function and dysfunction in the penis.
AB  - Endothelial nitric oxide (NO) synthase (eNOS) has an indispensable role in the
      erectile response. In the penis, eNOS activity and endothelial NO bioavailability
      are regulated by multiple post-translational molecular mechanisms, such as eNOS
      phosphorylation, eNOS interaction with regulatory proteins and contractile
      pathways, and actions of reactive oxygen species (ROS). These mechanisms regulate
      eNOS-mediated responses under physiologic circumstances and provide various
      mechanisms whereby endothelial NO availability may be altered in states of
      vasculogenic erectile dysfunction (ED). In view of the recent advances in the
      field of eNOS function in the penis and its role in penile erection, the emphasis
      in this review is placed on the mechanisms regulating eNOS activity and its
      interaction with the RhoA/Rho-kinase pathway in the physiology of penile erection
      and the pathophysiology of ED.

PMID- 16446493
TI  - Cardiac cytochrome-c oxidase deficiency occurs during late postnatal development
      in progeny of copper-deficient rats.
AB  - Although cytochrome-c oxidase (CCO) is a copper-dependent enzyme, the effect of
      maternal copper deficiency on the expression of CCO activity during postnatal
      development of the neonatal rat heart has not been investigated extensively.
      Here, we show that CCO activity in heart mitochondria isolated from neonates of
      copper-deficient dams did not exhibit significant reductions until postnatal days
      (PND) 15 and 21. In addition, immunoblot analysis indicated that the CCO subunit
      (Cox-1) was reduced on postnatal Days 10 and 21, and that Cox-4 was reduced on
      PND 21 in heart mitochondria of the neonates from copper-deficient dams. These
      findings indicate that the impairment of CCO activity in neonatal heart by
      maternal copper deficiency occurs late in the postnatal heart development.
      Furthermore, the concurrent reductions in Cox-1 and Cox-4 suggest that the
      impaired CCO activity reflects a CCO deficiency in heart mitochondria. CCO
      activity and Cox-1 in heart mitochondria were not fully restored by 6 weeks of
      postweaning copper repletion in the pups of copper-deficient dams. This indicates
      that prolonged maternal intake of moderately low dietary copper produces CCO
      deficiency in cardiac mitochondria of neonates during late postnatal heart
      development, after terminal differentiation of cardiomyocytes occurs. The
      resistance of CCO deficiency to repair by dietary copper supplementation may be
      related to the relatively slow turnover of the affected mitochondria in the
      terminally differentiated heart.

PMID- 16446495
TI  - Redox state and O2*- production in neutrophils of Crohn's disease patients.
AB  - The aim of this in vitro study was to evaluate the intracellular redox state and
      respiratory burst (RB) in neutrophils of patients with Crohn's disease (CD). The
      intracellular redox state and RB in neutrophils was assessed by the superoxide
      anion (O2*-) production induced in these cells after stimulation by various
      factors related to the molecular mechanisms that, if altered, may be responsible
      for an abnormal immune response. This can, in part, cause the onset of
      inflammation and tissue damage seen in CD. This study demonstrated a decreased
      glutathione/glutathione disulfide (GSH/GSSG) ratio index of an increased
      oxidative state in CD patient neutrophils. Moreover, our findings showed a
      decrease in tumor necrosis factor (TNF-alpha)- or phorbol 12-myristate 13-acetate
      (PMA)-induced O2*- production in CD patient neutrophils adherent to fibronectin
      as compared with controls. A decreased adhesion was also demonstrated. For this
      reason, the involvement of altered mechanisms of protein kinase C (PKC) and beta
      integrin activation in CD patient neutrophils is suggested. These data also
      showed that the harmful effects of TNF-alpha cannot be caused by excessive
      reactive oxygen species (ROS) production induced by neutrophils. Decreased cell
      viability after a prolonged time of adhesion (20 hrs) was also measured in CD
      patient neutrophils. The findings of this study demonstrate, for the first time,
      that granulocyte-macrophage colony-stimulating factor (GM-CSF), a compound
      recently used in CD therapy, is able to activate the RB for a prolonged time both
      in control and CD patient neutrophils. Increased viability of CD patient
      neutrophils caused by GM-CSF stimulation was also observed. In conclusion, our
      results indicate that decreased O2*- production and adhesion, caused, in part, by
      an anomalous response to TNF-alpha, together with low GSH level and low cell
      viability, may be responsible for the defective neutrophil function found in CD
      patients. This can contribute to the chronic inflammation and relapses that
      characterize this pathology. A possible role of GM-CSF in inducing O2*-
      production and in restoring the defensive role of neutrophils in CD patients is
      suggested.

PMID- 16446494
TI  - Cyclooxygenase products stimulate carbon monoxide production by piglet cerebral
      microvessels.
AB  - Products of arachidonic acid (AA) metabolism by cyclooxygenase (Cox) are
      important in regulation of neonatal cerebral circulation. The brain and cerebral
      microvessels also express heme oxygenase (HO) that metabolizes heme to carbon
      monoxide (CO), biliverdin, and iron. The purpose of this study in newborn pig
      cerebral microvessels was to address the hypothesis that Cox products affect HO
      activity and HO products affect Cox activity. AA (2.0-20 microM) increased
      prostaglandin E2 (PGE2) measured by radioimmunoassay (RIA) and also CO measured
      by gas chromatography/mass spectrometry (GC/MS). Further, 10(-4) M indomethacin,
      which inhibited Cox, reduced both AA and heme-induced CO production. Conversely,
      neither exogenous 2 x 10(-6) M heme, which markedly increased CO production, nor
      the inhibitor of HO, chromium mesoporphyrin, altered PGE2 synthesis. Because AA
      metabolism by Cox generates both prostanoids and superoxides, we determined the
      effects of the predominant prostanoid and superoxide on CO production. Although
      PGE2 caused a small increase in CO production, xanthine oxidase plus
      hypoxanthine, which produces superoxide, strongly stimulated the production of CO
      by cerebral microvessels. This increase was mildly attenuated by catalase. These
      data suggest that Cox-catalyzed AA metabolites, most likely superoxide and/or a
      subsequent reactive oxygen species, increase cerebrovascular CO production. This
      increase seems to be caused, at least in part, by the elevation of HO-2 catalytic
      activity. Conversely, Cox activity is not affected by HO-catalyzed heme
      metabolites. These data suggest that some cerebrovascular functions attributable
      to Cox activity could be mediated by CO.

PMID- 16446496
TI  - Renal thrombotic microangiopathy in a genetic model of hypertension in mice.
AB  - Our goal was to develop a model of accelerated hypertension with renal
      microangiopathy. Transgenic mice that are hypertensive because of overexpression
      of human renin (R+ mice) and human angiotensin (A+ mice) genes were studied. To
      increase arterial pressure to levels comparable to those that may be seen in
      malignant hypertension, high salt was added to the diet and/or the nitric oxide
      synthase inhibitor, N(omega)-nitro-L-arginine methylester (L-NAME), was added to
      the drinking water. Renal lesions, decline in renal function, and proteinuria
      developed within 10 weeks in R+/A+ mice given both L-NAME and a high-salt diet,
      and within 24 weeks in mice given either L-NAME or a high-salt diet. Renal
      morphology showed features of severe thrombotic microangiopathy, with extensive
      vascular and glomerular lesions in all R+/A+ mice on high salt, L-NAME, or high
      salt plus L-NAME. Vascular lesions included fibrin thrombi and onion skinning of
      the vessel walls, whereas glomerular lesions included segmental sclerosis,
      mesangiolysis, fibrin thrombi within glomerular capillaries, and double-contour
      formation of glomerular capillary walls. Renal morphology was normal in control
      mice fed high salt and/or L-NAME. No R+/A+ mice fed a normal diet developed
      vascular lesions, whereas a few mice developed mild focal glomerular lesions. In
      summary, these studies characterize vascular and glomerular lesions in R+/A+ mice
      fed high salt, L-NAME, or both high salt and L-NAME, and provide a murine model
      of malignant hypertension with renal thrombotic microangiopathy.

PMID- 16446497
TI  - DNA aptamers that bind to PrP(C) and not PrP(Sc) show sequence and structure
      specificity.
AB  - DNA aptamers were selected against recombinant human (rhu) cellular prion protein
      (PrP(C)) 23-231 by systematic evolution of ligands via a systematic evolution of
      ligands by exponential (SELEX) enrichment procedure using lateral flow
      chromatography. The SELEX procedure was performed with an aptamer library
      consisting of a randomized 40-nucleotide core flanked by 28-mer primer-binding
      sites that, theoretically, represented approximately 10(24) distinct nucleic acid
      species. Sixty nanograms of rhuPrP(C)23-231 immobilized in the center of a
      lateral flow device was used as the target molecule for SELEX. At the end of 6
      iterations of SELEX, 13 distinct candidate aptamers were identified, of which, 3
      aptamers represented 32%, 8%, and 5% of the sequences respectively. Eight
      aptamers, including the three most frequently occurring candidates, were selected
      for further evaluation. Selected aptamers bound to rhuPrP(C)23-231 at 10(-6) M to
      10(-8) M concentrations. Two of the eight aptamers bound at higher concentrations
      to rhuPrP(C)90-231. Theoretical thermodynamic modeling of selected aptamer
      sequences identified several common motifs among the selected aptamers that could
      play a role in PrP binding. Binding affinity to rhuPrP(C)23-231 was both aptamer
      sequence and structure dependent. Further, selected aptamers bound to mammalian
      PrPs derived from brain of healthy sheep, calf, piglet, and deer, and to PrP(C)
      expressed in mouse neuroblastoma cells. None of the aptamers bound to proteinase
      K-digested scrapie-infected mouse neuroblastoma cells or untreated PrP-null
      cells, which further confirmed the PrP(C) specificity of the aptamers. In
      summary, we enriched and selected DNA aptamers that bind specifically to
      rhuPrP(C) and mammalian PrP(C) with varying affinities and can be applied to
      biological samples for PrP(C) enrichment and as diagnostic tools in double ligand
      assay systems.

PMID- 16446498
TI  - Resibufogenin corrects hypertension in a rat model of human preeclampsia.
AB  - The study of the pathogenesis of preeclampsia has been hampered by a relative
      dearth of animal models. We developed a rat model of preeclampsia in which the
      excretion of a circulating inhibitor of Na/K ATPase, marinobufagenin (MBG), is
      elevated. These animals develop hypertension, proteinuria, and intrauterine
      growth restriction. The administration of a congener of MBG, resibufogenin (RBG),
      reduces blood pressure to normal in these animals, as is the case when given to
      pregnant animals rendered hypertensive by the administration of MBG. Studies of
      Na/K ATPase inhibition by MBG and RBG reveal that these agents are equally
      effective as inhibitors of the enzyme.

PMID- 16446499
TI  - Suspected myotoxicity of edible wild mushrooms.
AB  - Recently, the widely consumed yellow tricholoma Tricholoma flavovirens caused
      delayed rhabdomyolysis and fatalities in humans in France and Poland and
      triggered elevated plasma creatine kinase activities in mice. Furthermore, the
      highly appreciated king boletus (Boletus edulis) caused similar responses in
      experimental mice. Because of this, it was hypothesized that other fungi could
      also contain chemical compounds that would cause similar myotoxic effects. To
      test the suspected myotoxicity of other wild mushrooms consumed by tradition, 86
      mice were exposed for 5 days to 3, 6, or 9 g/kg body mass/day of edible mushrooms
      representing diverse genera (Russula spp, Cantharellus cibarius, Albatrellus
      ovinus, and Leccinium versipelle) mixed with regular laboratory rodent diet. The
      plasma creatine kinase activity increased with all studied mushroom species at 9
      g/kg body mass/day, whereas the histologic appearance of muscle and liver samples
      was unaffected. The results support the hypothesis that the previously observed
      toxic effects are not specific to T. flavovirens, but probably represent an
      unspecific response requiring individual sensitivity and a significant amount of
      ingested mushroom to manifest itself.

PMID- 16446500
TI  - The 59th Symposium of the Society of General Physiologists. Na,K-ATPase and
      related cation pumps: structures, mechanisms, and diseases.

PMID- 16446501
TI  - Functions of stretch activation in heart muscle.

PMID- 16446502
TI  - Activation dependence of stretch activation in mouse skinned myocardium:
      implications for ventricular function.
AB  - Recent evidence suggests that ventricular ejection is partly powered by a delayed
      development of force, i.e., stretch activation, in regions of the ventricular
      wall due to stretch resulting from torsional twist of the ventricle around the
      apex-to-base axis. Given the potential importance of stretch activation in
      cardiac function, we characterized the stretch activation response and its Ca2+
      dependence in murine skinned myocardium at 22 degrees C in solutions of varying
      Ca2+ concentrations. Stretch activation was induced by suddenly imposing a
      stretch of 0.5-2.5% of initial length to the isometrically contracting muscle and
      then holding the muscle at the new length. The force response to stretch was
      multiphasic: force initially increased in proportion to the amount of stretch,
      reached a peak, and then declined to a minimum before redeveloping to a new
      steady level. This last phase of the response is the delayed force characteristic
      of myocardial stretch activation and is presumably due to increased attachment of
      cross-bridges as a consequence of stretch. The amplitude and rate of stretch
      activation varied with Ca2+ concentration and more specifically with the level of
      isometric force prior to the stretch. Since myocardial force is regulated both by
      Ca2+ binding to troponin-C and cross-bridge binding to thin filaments, we
      explored the role of cross-bridge binding in the stretch activation response
      using NEM-S1, a strong-binding, non-force-generating derivative of myosin
      subfragment 1. NEM-S1 treatment at submaximal Ca2+-activated isometric forces
      significantly accelerated the rate of the stretch activation response and reduced
      its amplitude. These data show that the rate and amplitude of myocardial stretch
      activation vary with the level of activation and that stretch activation involves
      cooperative binding of cross-bridges to the thin filament. Such a mechanism would
      contribute to increased systolic ejection in response to increased delivery of
      activator Ca2+ during excitation-contraction coupling.

PMID- 16446503
TI  - Different transport mechanisms in plant and human AMT/Rh-type ammonium
      transporters.
AB  - The conserved family of AMT/Rh proteins facilitates ammonium transport across
      animal, plant, and microbial membranes. A bacterial homologue, AmtB, forms a
      channel-like structure and appears to function as an NH3 gas channel. To evaluate
      the function of eukaryotic homologues, the human RhCG glycoprotein and the tomato
      plant ammonium transporter LeAMT1;2 were expressed and compared in Xenopus
      oocytes and yeast. RhCG mediated the electroneutral transport of methylammonium
      (MeA), which saturated with Km = 3.8 mM at pHo 7.5. Uptake was strongly favored
      by increasing the pHo and was inhibited by ammonium. Ammonium induced rapid
      cytosolic alkalinization in RhCG-expressing oocytes. Additionally, RhCG
      expression was associated with an alkali-cation conductance, which was not
      significantly permeable to NH4+ and was apparently uncoupled from the ammonium
      transport. In contrast, expression of the homologous LeAMT1;2 induced pHo
      independent MeA+ uptake and specific NH4+ and MeA+ currents that were distinct
      from endogenous currents. The different mechanisms of transport, including the
      RhCG-associated alkali-cation conductance, were verified by heterologous
      expression in appropriate yeast strains. Thus, homologous AMT/Rh-type proteins
      function in a distinct manner; while LeAMT1;2 carries specifically NH4+, or
      cotransports NH3/H+, RhCG mediates electroneutral NH3 transport.

PMID- 16446504
TI  - Identification of a disulfide bridge linking the fourth and the seventh
      extracellular loops of the Na+/glucose cotransporter.
AB  - The Na+/glucose cotransporter (SGLT1) is an archetype for the SLC5 family, which
      is comprised of Na+-coupled transporters for sugars, myo-inositol, choline, and
      organic anions. Application of the reducing agent dithriothreitol (DTT, 10 mM) to
      oocytes expressing human SGLT1 affects the protein's presteady-state currents.
      Integration of these currents at different membrane potentials (Vm) produces a Q
      V curve, whose form was shifted by +25 mV due to DTT. The role of the 15
      endogenous cysteine residues was investigated by expressing SGLT1 constructs,
      each bearing a single mutation for an individual cysteine, in Xenopus oocytes,
      using two-microelectrode voltage-clamp electrophysiology and fluorescent
      labeling. 12 of the 15 mutants were functional and could be separated into three
      distinct groups based on the effect of the mutation on the Q-V curve: four
      mutants did not perturb the transferred charge, six mutants shifted the Q-V curve
      towards negative potentials, and two mutants (C255A and C511A) produced a shift
      in the positive direction that was identical to the shift produced by DTT on the
      wild-type (wt) SGLT1. The double mutant C(255,511)A confirms that the effects of
      each single mutant on the Q-V curve were not additive. With respect to wt SGLT1,
      the apparent affinities for alpha-methylglucose (alphaMG) were increased in a
      similar manner for the single mutants C255A and C511A, the double mutant
      C(255,511)A as well as for wt SGLT1 treated with DTT. When exposed to a maleimide
      based fluorescent probe, wt SGLT1 was not significantly labeled but mutants C255A
      and C511A could be clearly labeled, indicating an accessible cysteine residue.
      These residues are presumed to be C511 and C255, respectively, as the double
      mutant C(255,511)A could not be labeled. These results strongly support the
      hypothesis that C255 and C511 form a disulfide bridge in human SGLT1 and that
      this disulfide bridge is involved in the conformational change of the free
      carrier.

PMID- 16446506
TI  - Distinct populations of HCN pacemaker channels produce voltage-dependent and
      voltage-independent currents.
AB  - Hyperpolarization-activated HCN pacemaker channels are critical for the
      generation of spontaneous activity and the regulation of excitability in the
      heart and in many types of neurons. These channels produce both a voltage
      dependent current (I(h)) and a voltage-independent current (I(inst) or VIC). In
      this study, we explored the molecular basis of the voltage-independent current.
      We found that for the spHCN isoform, VIC averaged approximately 4% of the maximum
      HCN conductance that could be activated by hyperpolarization. Cyclic AMP
      increased the voltage-independent current in spHCN to approximately 8% of
      maximum. In HCN2, VIC was approximately 2% of the maximal current, and was little
      affected by cAMP. VIC in both spHCN and HCN2 was blocked rapidly both by ZD7288
      (an HCN channel blocker that is thought to bind in the conduction pore) and by
      application of Cd2+ to channels containing an introduced cysteine in the pore
      (spHCN-464C or HCN2-436C). These results suggest that VIC flows through the main
      conduction pathway, down the central axis of the protein. We suspected that VIC
      simply represented a nonzero limiting open probability for HCN channels at
      positive voltages. Surprisingly, we found instead that the spHCN channels
      carrying VIC were not in rapid equilibrium with the channels carrying the voltage
      dependent current, because they could be blocked independently; a single
      application of blocker at a depolarized potential essentially eliminated VIC with
      little change in I(h). Thus, VIC appears to be produced by a distinct population
      of HCN channels. This voltage-independent current could contribute significantly
      to the role of HCN channels in neurons and myocytes; VIC flowing through the
      channels at physiological potentials would tend to promote excitability by
      accelerating both depolarization and repolarization.

PMID- 16446505
TI  - Mini-dystrophin expression down-regulates overactivation of G protein-mediated
      IP3 signaling pathway in dystrophin-deficient muscle cells.
AB  - We present here evidence for the enhancement of an inositol 1,4,5-trisphosphate
      (IP3) mediated calcium signaling pathway in myotubes from dystrophin-deficient
      cell lines (SolC1(-)) as compared to a cell line from the same origin but
      transfected with mini-dystrophin (SolD(+)). With confocal microscopy, we
      demonstrated that calcium rise, induced by the perifusion of a solution
      containing a high potassium concentration, was higher in SolC1(-) than in SolD(+)
      myotubes. The analysis of amplitude and kinetics of the calcium increase in
      SolC1(-) and in SolD(+) myotubes during the exposure with SR Ca2+ channel
      inhibitors (ryanodine and 2-APB) suggested the presence of two mechanisms of SR
      calcium release: (1) a fast SR calcium release that depended on ryanodine
      receptors and (2) a slow SR calcium release mediated by IP3 receptors. Detection
      analyses of mRNAs (reverse transcriptase [RT]-PCR) and proteins (Western blot and
      immunolocalization) demonstrated the presence of the three known isoforms of IP3
      receptors in both SolC1(-) and SolD(+) myotubes. Furthermore, analysis of the
      kinetics of the rise in calcium revealed that the slow IP3-dependent release may
      be increased in the SolC1(-) as compared to the SolD(+), suggesting an inhibitory
      effect of mini-dystrophin in this signaling pathway. Upon incubation with
      pertussis toxin (PTX), an inhibitory effect similar to that of the IP3R inhibitor
      (2-APB) was observed on K+-evoked calcium release. This result suggests the
      involvement of a Gi protein upstream of the IP3 pathway in these stimulation
      conditions. A hypothetical model is depicted in which both Gi protein and IP3
      production could be involved in K+-evoked calcium release as well as a possible
      interaction with mini-dystrophin. Our findings demonstrate the existence of a
      potential relationship between mini-dystrophin and SR calcium release as well as
      a regulatory role of mini-dystrophin on intracellular signaling.

PMID- 16446507
TI  - Structural determinants for functional coupling between the beta and alpha
      subunits in the Ca2+-activated K+ (BK) channel.
AB  - High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels
      are widely expressed in mammals. In some tissues, the biophysical properties of
      BK channels are highly affected by coexpression of regulatory (beta) subunits.
      The most remarkable effects of beta1 and beta2 subunits are an increase of the
      calcium sensitivity and the slow down of channel kinetics. However, the detailed
      characteristics of channels formed by alpha and beta1 or beta2 are dissimilar,
      the most remarkable difference being a reduction of the voltage sensitivity in
      the presence of beta1 but not beta2. Here we reveal the molecular regions in
      these beta subunits that determine their differential functional coupling with
      the pore-forming alpha-subunit. We made chimeric constructs between beta1 and
      beta2 subunits, and BK channels formed by alpha and chimeric beta subunits were
      expressed in Xenopus laevis oocytes. The electrophysiological characteristics of
      the resulting channels were determined using the patch clamp technique. Chimeric
      exchange of the different regions of the beta1 and beta2 subunits demonstrates
      that the NH3 and COOH termini are the most relevant regions in defining the
      behavior of either subunit. This strongly suggests that the intracellular domains
      are crucial for the fine tuning of the effects of these beta subunits. Moreover,
      the intracellular domains of beta1 are responsible for the reduction of the BK
      channel voltage dependence. This agrees with previous studies that suggested the
      intracellular regions of the alpha-subunit to be the target of the modulation by
      the beta1-subunit.

PMID- 16446508
TI  - A Na+- and Cl- -activated K+ channel in the thick ascending limb of mouse kidney.
AB  - This study investigates the presence and properties of Na+-activated K+ (K(Na))
      channels in epithelial renal cells. Using real-time PCR on mouse microdissected
      nephron segments, we show that Slo2.2 mRNA, which encodes for the K(Na) channels
      of excitable cells, is expressed in the medullary and cortical thick ascending
      limbs of Henle's loop, but not in the other parts of the nephron. Patch-clamp
      analysis revealed the presence of a high conductance K+ channel in the
      basolateral membrane of both the medullary and cortical thick ascending limbs.
      This channel was highly K+ selective (P(K)/P(Na) approximately 20), its
      conductance ranged from 140 to 180 pS with subconductance levels, and its
      current/voltage relationship displayed intermediate, Na+-dependent, inward
      rectification. Internal Na+ and Cl- activated the channel with 50% effective
      concentrations (EC50) and Hill coefficients (nH) of 30 +/- 1 mM and 3.9 +/- 0.5
      for internal Na+, and 35 +/- 10 mM and 1.3 +/- 0.25 for internal Cl-. Channel
      activity was unaltered by internal ATP (2 mM) and by internal pH, but clearly
      decreased when internal free Ca2+ concentration increased. This is the first
      demonstration of the presence in the epithelial cell membrane of a functional,
      Na+-activated, large-conductance K+ channel that closely resembles native K(Na)
      channels of excitable cells. This Slo2.2 type, Na+- and Cl--activated K+ channel
      is primarily located in the thick ascending limb, a major renal site of
      transcellular NaCl reabsorption.

PMID- 16446510
TI  - Percutaneous coronary intervention in anomalous right coronary arteries arising
      from the left sinus of Valsalva: a report of two cases and observations on the
      pattern of atherosclerosis.

PMID- 16446511
TI  - Late "adult form" scimitar syndrome presenting with "infant form" complications.
AB  - This case report describes an 85-year-old woman with complications resulting from
      scimitar syndrome, anomalous drainage of the right pulmonary veins into the
      inferior vena cava. In addition to being the oldest reported case of this
      congenital anomaly, this is the first report of pulmonary vascular complications
      from scimitar manifested in the adult. The magnitude of the vascular shunt and
      advanced nature of the disease precluded surgical or percutaneous intervention in
      this patient.

PMID- 16446512
TI  - Procedural success and 30 day outcomes between CYPHER and TAXUS stent
      implantation for the treatment of bifurcation lesions--a single-center
      experience.
AB  - BACKGROUND: There are fundamental differences between the CYPHER and TAXUS
      stents, including the drug coatings, polymers and stent platforms. In this
      registry study, we sought to investigate the procedural success and 30-day
      outcomes of the patients who were treated with either the CYPHER or TAXUS stents
      for de novo bifurcation lesions. METHODS: A total of 83 patients with 85 de novo
      bifurcation lesions treated with either the CYPHER or TAXUS stents from June 2002
      to May 2004 were recruited for analysis. RESULTS: True bifurcation lesion,
      stenosis in both the main vessel and side branch, constituted 39% of the treated
      lesions. The procedural success was 96% and 93% in CYPHER and TAXUS groups,
      respectively. Bifurcation stenting was performed in 13% of the overall study
      population. Two patients each in the CYPHER (8%) and TAXUS (3%) groups had a
      slight elevation of cardiac enzymes after the procedure. At 30-day follow up, 2
      patients in the TAXUS and none in the CYPHER group had subacute stent thrombosis
      (SAT), leading to myocardial infarction (MI). Urgent target vessel
      revascularization (TVR) was attempted in these 2 patients, but failed in 1 of
      them. A total of 6 adverse events (1 stroke, 2 MIs and 3 TVRs) from 4 patients (2
      patients with 2 adverse events) in the TAXUS group, and 1 adverse event (TVR) in
      the CYPHER group were reported. The adverse event rate was slightly, but not
      significantly, higher in the TAXUS group (7% vs. 4%; p = 1.000). CONCLUSION: Our
      results suggest that the procedural success and 30-day outcomes were similar in
      patients who had been treated with either the CYPHER or TAXUS stent for de novo
      bifurcation lesions. The occurrence of SAT in the TAXUS but not in the CYPHER
      group warrants further evaluation.

PMID- 16446513
TI  - Bifurcation intervention: keep it simple.

PMID- 16446514
TI  - Early ambulation and variability in anticoagulation during elective coronary
      stenting with a single intravenous bolus of low-dose, low-molecular weight
      heparin enoxaparin.
AB  - BACKGROUND: The best anticoagulation strategy for patients undergoing
      percutaneous coronary intervention (PCI) remains controversial. The primary
      objective of this study was to assess the feasibility of immediate sheath removal
      post-PCI in patients given a single low-dose intravenous (IV) bolus of enoxaparin
      as the sole anticoagulant. METHODS: In 53 patients with stable coronary disease
      undergoing elective PCI, a single IV bolus of 0.5 mg per kg enoxaparin was
      administered 10 minutes before PCI. Patients were pretreated with aspirin 100 mg
      and clopidogrel 300 mg. The femoral access sheaths were removed immediately after
      PCI by manual compression. Major and minor bleeding and coronary thrombosis were
      recorded. Anti-Xa levels were measured before, during and after PCI. RESULTS: One
      patient had an intracoronary thrombus 60 minutes after enoxaparin administration,
      and there was 1 ischemic stroke. Fifty-one of the 53 patients had their sheaths
      successfully pulled immediately post-PCI. One patient had a pseudoaneurysm
      requiring surgical repair, and 1 patient had a minor bleed. Postprocedural
      elevation of CK-MB > 3 times the upper limit of normal occurred in 7 patients
      (13.2%). Anti-Xa activity was 0.56 +/- 0.16 at 10 minutes post-IV injection, and
      then progressively decreased to 0.14 +/- 0.09 IU/ml at 6 hours after injection.
      Ten minutes after IV enoxaparin, 12 patients (23.5%) had anti-Xa levels < 0.5
      IU/ml. CONCLUSIONS: Immediate removal of femoral sheaths, after a single low-dose
      of IV enoxaparin for elective stenting appears feasible. However, a sizeable
      proportion of patients achieved anti-Xa levels below the widely agreed upon
      "therapeutic" level after injection.

PMID- 16446515
TI  - Clinical and economic outcomes of embolic complications and strategies for distal
      embolic protection during percutaneous coronary intervention in saphenous vein
      grafts.
AB  - BACKGROUND: Although distal embolic protection (DEP) is increasingly utilized in
      saphenous vein graft percutaneous coronary intervention (SVG PCI), the clinical
      and economic outcomes of different DEP strategies are unknown. METHODS: We
      compared 3 DEP strategies (no DEP, routine DEP, selective DEP in high-risk cases)
      in 126 consecutive cases of SVG PCI performed without DEP in a single
      catheterization laboratory over a 4-year period. No SVG PCI was excluded. High
      risk was defined using 2 multivariate predictors of embolic complication
      previously validated by NCDR (graft age greater than or equal to 8 years and or
      friable appearance with thrombus). Costs were determined by a ratio of cost-to
      charges methodology and average cost of the two FDA-approved DEP devices ($1,350)
      with similar efficacy. RESULTS: Without DEP, the incidence of embolic
      complications was 17% (22/126), resulting in major adverse coronary events (MACE)
      in 3.2% (4/126) of all cases: 2 deaths, 1 myocardial infarction, and 1 emergency
      coronary artery bypass. Embolic complications significantly increased both
      procedure costs by $2,725 (p < .001) and total hospital costs approximately
      $2,800 (p < 0.05). Risk adjustment for selective DEP use correctly predicted 86%
      (19/22) of embolic complications, including all MACE, at an incremental cost of
      $684 per patient for selective DEP versus $1,150 per patient for routine DEP.
      Selective DEP would cost $43,127 per death prevented versus $72,461 using routine
      DEP during the index hospitalization. CONCLUSIONS: Embolic complications increase
      cost in excess of the cost of a DEP device. This risk adjustment model correctly
      predicted the majority of cases of embolic complication and all MACE, suggesting
      that selective DEP use may help reduce utilization of DEP by an almost 50% cost
      reduction compared to routine use.

PMID- 16446516
TI  - Percutaneous transvenous mitral commissurotomy using metallic commissurotome:
      long-term follow-up results.
AB  - BACKGROUND: We report the long-term follow-up results of percutaneous transvenous
      mitral commissurotomy (PTMC) using metallic commissurotome, which is proposed as
      an alternative to Inoue balloon use. METHODS: PTMC using a metallic
      commissurotome was performed in 248 patients (65 men) by the anterograde
      transseptal technique. Of the 248, 64 of the procedures were for mitral
      restenosis after previous valvotomy. RESULTS: The procedure was successful in 230
      patients (92.7%). Following PTMC, the transmitral gradient decreased from 14.54
      +/- 5.79 mmHg to 4.26 +/- 2.82 mmHg (p less than or equal to 0.001). The mitral
      valve area (MVA) increased from 0.85 +/- 0.12 cm2 to 1.95 +/- 0.31 cm2 (p less
      than or equal to 0.001). One patient died due to left ventricular perforation
      (mortality rate = 0.41%). Another patient who developed a left ventricular tear
      underwent repair of the tear along with open mitral valvotomy. Four patients
      developed significant mitral regurgitation (MR) from a tear of valve leaflets and
      had to undergo emergency mitral valve replacement. One patient had a transient
      ischemic attack and 5 patients developed moderate MR caused by excessive split of
      valve commissures. The mean follow up period was 3.34 +/- 0.66 years. Six
      patients were lost to follow up. Seven of the remaining 224 patients developed
      mitral restenosis. At follow up, the mean pressure gradient across the mitral
      valve assessed by echocardiography was 6.09 +/- 3.12 mmHg. The mean mitral valve
      area decreased to 1.67 +/- 0.34 cm2, but clinical improvement persisted in most
      of the patients. CONCLUSION: PTMC with metallic commissurotomy is safe and
      produced good results which were sustained at a follow-up period of more than 3
      years.

PMID- 16446517
TI  - Glycoprotein IIb/IIIa inhibitors during rescue percutaneous coronary intervention
      in acute myocardial infarction.
AB  - Although percutaneous coronary intervention (PCI) following full-dose
      thrombolytic therapy (rescue angioplasty) is a common procedure, there is ample
      controversy regarding the usefulness of the procedure. Moreover, few data are
      available concerning the safety and efficacy of concomitant treatment with
      glycoprotein (GP) IIb/IIIa inhibitors in these patients. The aim of the present
      study was to compare the clinical outcomes of patients who underwent rescue PCI
      with stents and were treated with GP IIb/IIIa inhibitors. A total of 59
      consecutive patients underwent rescue PCI at our institution during the study
      period, 29 patients (49.2%) were treated concomitantly with a GP IIb/IIIa
      inhibitor and 30 patients (50.8%) were not. Baseline clinical characteristics
      were similar between the two groups. In-hospital outcomes regarding death,
      reinfarction and the need for urgent target vessel revascularization was
      significantly lower in patients treated with GP IIb/IIIa inhibitors compared to
      those who were not treated (3.4% vs. 26.7%; p = 0.01, respectively). However, GP
      IIb/IIIa inhibitor administration was not an independent predictor of better
      outcomes by multivariate analysis. There was a higher rate of major bleeding
      complications in patients who received GP IIb/IIIa inhibitors, though it did not
      achieve statistical significance (6.9% vs. 0%; p = 0.14, respectively). The
      composite endpoint of major, minor bleeding and vascular complications was
      similar in both groups (24.1% vs. 16.7%; p = 0.48). In conclusion, the
      administration of GP IIb/IIIa inhibitors in patients undergoing rescue PCI after
      failed thrombolysis with stents was safe and may have a beneficial effect on 30
      day event-free survival rates, without a significant increase in bleeding or
      vascular complications. These results warrant further investigation.

PMID- 16446518
TI  - Adjunctive antiplatelet therapy during rescue PCI.

PMID- 16446519
TI  - Sequential balloon dilatation for combined aortic valvular stenosis and
      coarctation of the aorta in a single catheterization procedure: a prognostic
      evaluation based on long-term follow up.
AB  - BACKGROUND: Combined aortic valvular stenosis (AVS) and coarctation of the aorta
      (CoA) is uncommon. There are only a few case reports that discuss the treatment
      choices and prognosis. We present the immediate and long-term results for a group
      of children with combined AVS and CoA who underwent sequential percutaneous
      balloon dilatation in a single catheterization procedure. PATIENTS AND METHODS:
      The cases of 13 children with combined AVS and CoA who underwent balloon
      dilatation in a single catheterization session between August 1995 and May 2002
      were retrospectively evaluated. The group was comprised of 9 boys and 4 girls of
      mean age 14.9 +/- 24.2 months (range = 19 days to 7 years). RESULTS: The pressure
      gradients at the valvular level before and after the intervention were 51.5 +/-
      22.3 mmHg (range = 8 to 85 mmHg) and 22.4 +/- 18.3 mmHg (range = 2 to 57 mmHg),
      respectively (p < 0.001). The corresponding findings for the coarctation segment
      were 22.3 +/- 13.5 mmHg (range = 0 to 45 mmHg), and 5.2 +/- 7.0 mmHg (range = 0
      to 24 mmHg; p < 0.001). After the intervention, mild aortic regurgitation
      occurred in 5 children (38.5%). Mild aortic regurgitation became moderate in 1
      patient (7.7%). Three patients developed peripheral arterial occlusion treated
      with heparin and streptokinase after intervention. There were no deaths during or
      early after the procedures. Four patients (30.8%) died, all in the first 6 months
      after the intervention, and the mean follow-up time for the 9 survivors was 57.6
      +/- 38.9 months (range = 6 to 107 months). Recurrence of stenosis and coarctation
      occurred in 2 (15.4%) and 4 (30.8%) cases, respectively. Four patients (30.8%)
      underwent cardiac surgery. The event-free survival rates were 76.9% at 6 months,
      61.5% at 12 months through 24 months, and 30.8% at 60 months. The overall
      survival rates were 76.9% at 3 months, 69.2% at 6 months, and it remained 69.2%
      for the rest of the follow-up period. NOTE: Outcomes for 13 patients with
      combined AVS and CoA who underwent single-session sequential balloon dilatation
      are described. The results were favorable; there were no severe complications
      related to the procedures, and no deaths occurred during or in the early period
      after the intervention.

PMID- 16446520
TI  - Biodegradable stents: they do their job and disappear.
AB  - Despite the development and progression of metallic stents, many concerns still
      remain because of their permanent nature. Although metallic stents are effective
      in preventing recoil and late restenosis after coronary angioplasty, they
      continue to have limitations such as stent thrombosis and mismatch of the stent
      to the vessel size. Thus, the concept of bioabsorbable stents has emerged as an
      alternative to permanent metal stents. This review will outline concepts,
      material designs, preclinical, and initial clinical experimental studies with
      bioabsorbable stents.

PMID- 16446521
TI  - Percutaneous retrograde revascularization of lower extremity vessels by using the
      dorsalis pedis artery: two case reports.

PMID- 16446522
TI  - Coronary bifurcation stenting: from crush to culotte. Avoiding limerence and meme
      propagation.

PMID- 16446523
TI  - Novel intracoronary steerable support catheter for complex coronary intervention.

PMID- 16446524
TI  - Saphenous vein graft rheology simulating a thrombotic lesion.

PMID- 16446525
TI  - Refractory hypoxemia after mitral valve surgery: an unusual cause and its
      successful percutaneous treatment.
AB  - We describe the case of a patient who underwent elective mitral valve replacement
      and whose postoperative progress was complicated by a persistently high inspired
      oxygen requirement and consequent inability to wean from respiratory support. The
      reason for this was initially unclear, but transesophageal echocardiography
      identified the cause as a postoperative iatrogenic atrial septal defect (ASD).
      This complication was specifically related to the transseptal surgical approach
      that had been employed. The refractory arterial hypoxemia encountered
      postoperatively was due to an element of right-to-left shunting across the
      defect, in the absence of raised pulmonary artery pressures, likely related to a
      baffle-like effect of the residual atrial septal tissue. This postulated
      mechanism was supported both by Doppler color flow mapping across the defect at
      transesophageal echocardiography, and later by observing a rise in systemic
      arterial oxygen saturations immediately after device closure of the ASD. Once the
      iatrogenic ASD had been diagnosed, there was a consensus of opinion that the
      patient was too unwell to survive further open heart surgery. Hence, percutaneous
      closure of the defect was performed using an Amplatzer occluder device. This was
      technically successful and led to a marked improvement in the patient's clinical
      state, subsequent rapid weaning from ventilatory support and later hospital
      discharge. This case illustrates a rare presentation of an occasional
      complication of mitral valve surgery. Percutaneously delivered device closure of
      the ASD proved highly effective in this patient for whom no other options were
      felt to be feasible.

PMID- 16446527
TI  - Treatment of spontaneous coronary dissection with drug-eluting stents--late
      clinical, angiographic and IVUS follow up.
AB  - The prognosis of spontaneous coronary artery dissection is uncertain and optimal
      treatment is unknown. We previously described the first reported implantation of
      drug-eluting stents in spontaneous coronary artery dissection. The immediate
      angiographic result was good, and we now report the late clinical, angiographic
      and intravascular ultrasound follow up.

PMID- 16446526
TI  - Mechanical reperfusion during acute myocardial infarction in a patient with
      dextrocardia.
AB  - Mechanical reperfusion is the preferred treatment for acute ST-elevation
      myocardial infarction, we describe a case of successful primary angioplasty and
      stenting in a patient with dextrocardia and situs inversus. Dextrocardia with
      complete situs inversus is a rare condition, occurring in about 2 in 10,000 live
      births. However, ischemic heart disease and myocardial infarction have been
      reported in patients with dextrocardia, and hence the coexistence of myocardial
      infarction and dextrocardia is not unusual. The incidence of atherosclerosis in
      this group is not known, but is considered to be the same as that in the general
      population. There have been a few reports of percutaneous coronary intervention
      in these patients. We describe a case of primary angioplasty and stenting in a
      patient with dextrocardia and situs inversus and the electrocardiographic
      correlation of successful myocardial reperfusion.

PMID- 16446528
TI  - Refractory coronary vasospasm following drug-eluting stent placement treated with
      cyproheptadine.
AB  - Serotonin (5-hydroxytryptamine) has been recently shown to be an important
      mediator of coronary vasospasm. Its divergent effect on normal and
      atherosclerosed arteries has been demonstrated in both animal and human studies.
      We present a case of coronary vasospasm in a 55-year-old man with repeated
      episodes of chest pain following coronary percutaneous intervention. Repeat
      angiography demonstrated no reocclusion or complication. The patient's symptoms
      were resistant to treatment with maximum doses of two calcium channel antagonists
      and oral and intravenous nitrates, but responded to cyproheptadine, a
      nonselective serotonin antagonist. Currently, there are only two reported cases
      of coronary vasospasm following balloon angioplasty responding to treatment with
      serotonin antagonists. This is the first case reported case following drug
      eluting stent deployment.

PMID- 16446529
TI  - Fibromuscular dysplasia and acute myocardial infarction: evidence for a unique
      clinical and angiographic pattern.
AB  - Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic disease of
      the small- to medium-sized vessels that primarily affects young females in their
      second to fourth decades of life. Typically, FMD involves the renal and
      extracranial arteries, but at autopsy, it has also been reported to affect the
      coronary arteries. However, its association with acute coronary syndromes is not
      yet well recognized. We describe three cases of FMD that presented with an acute
      myocardial infarction as the initial manifestation and discuss a specific pattern
      found in all cases as well as the possible patholophysiologic mechanism
      responsible for the acute coronary syndrome.

PMID- 16446530
TI  - A prospective analysis of 184 hemoptysis cases: diagnostic impact of chest X-ray,
      computed tomography, bronchoscopy.
AB  - BACKGROUND: The clinical presentation of hemoptysis often raises a number of
      diagnostic possibilities. OBJECTIVES: This study was designed to evaluate the
      relative frequency of different causes of hemoptysis and the value of chest
      radiography, computed tomography (CT) scanning and fiber-optic bronchoscopy in
      the evaluation of a Greek cohort population. METHODS: We prospectively followed a
      total of 184 consecutive patients (137 males/47 females, 145 smokers/39
      nonsmokers) admitted with hemoptysis between January 2001 and December 2003 to
      the University Hospital of Heraklion. Follow-up data were collected on August
      2005. RESULTS: The main causes of hemoptysis were bronchiectasis (26%), chronic
      bronchitis (23%), acute bronchitis (15%) and lung cancer (13%). Bronchiectasis
      was significantly more frequent in nonsmokers (p < 0.02). Among nonsmokers,
      patients with moderate/severe bleeding or a history of tuberculosis were more
      likely to have bronchiectasis (OR 8.25; 95% CI 1.9-35.9, p = 0.007 and OR 16.5;
      95% CI 1.7-159.1, p = 0.007, respectively). Nonsmokers with normal or abnormal X
      rays were equally likely to have bronchiectasis (OR 2.5; 95% CI 0.66-9.39, p =
      0.2). Lung cancer was only found in smokers. Smokers with normal X-rays were less
      likely to have lung cancer compared to smokers with abnormal X-ray (OR 5.4; 95%
      CI 1.54-19.34, p = 0.004). There were no smokers with normal CT and lung cancer.
      Follow-up data were collected in 91% of patients. Lung cancer did not develop in
      any patient assumed to have hemoptysis of another origin than lung cancer on
      initial evaluation. CONCLUSIONS: Bronchiectasis is the main diagnosis in patients
      admitted with hemoptysis to a Greek University Hospital and it is more frequent
      among nonsmokers with moderate/severe bleeding and/or previous tuberculosis
      infection. Nonsmokers with moderate/severe hemoptysis and/or a history of
      tuberculosis should be evaluated with high-resolution CT. Smokers with hemoptysis
      are at increased risk for lung cancer and need to be extensively evaluated with
      chest CT and bronchoscopy.

PMID- 16446531
TI  - Chymase gene (CMA1) polymorphisms in Dutch and Japanese sarcoidosis patients.
AB  - BACKGROUND: Chymase is released from mast cells following activation. Evidence
      suggests that chymase plays an important role in tissue injury and remodeling of
      the lungs, heart and skin. OBJECTIVE: We postulated that chymase gene (CMA1)
      polymorphisms are associated with pulmonary fibrosis in Dutch and with cardiac
      and skin involvement in Japanese sarcoidosis patients. PATIENTS AND METHODS:
      Dutch (n = 153) and Japanese (n = 122) sarcoidosis patients with controls (Dutch,
      n = 309; Japanese, n = 111) were studied. Pulmonary involvement in Dutch patients
      as well as clinical manifestations in Japanese patients was evaluated for
      association with five CMA1 polymorphisms. RESULTS: The CMA1 polymorphisms were
      not associated with disease susceptibility in either population, or with
      radiographic evolution in the Dutch or with cardiac or skin involvement in the
      Japanese patients. The -526 T allele was associated with a lower iVC in Dutch
      patients. CONCLUSIONS: The CMA1 polymorphisms studied do not contribute to
      disease susceptibility in Japanese or Dutch sarcoidosis patients. CMA1
      polymorphisms do not influence radiographic evolution in Dutch sarcoidosis
      patients, nor do they predispose to cardiac or skin involvement in Japanese
      patients. However, the association between CMA1 -526 C/T and iVC in the Dutch
      patients suggests that chymase may modify the functional outcome of pulmonary
      sarcoidosis.

PMID- 16446532
TI  - Is a miliary chest pattern always indicative of tuberculosis or malignancy?

PMID- 16446533
TI  - External and extreme capsular stroke: clinical, topographical and etiological
      patterns.
AB  - BACKGROUND AND PURPOSE: To characterize clinically acute external (EcC) and
      extreme capsular (ExC) strokes in 9 patients with first-ever acute stroke.
      METHODS: Nine patients with a lesion limited to the EcC-ExC region proven by
      diffusion-weighted imaging included in our registry, corresponding to 0.3% of
      3,600 patients with ischemic stroke, were studied. RESULTS: We found three main
      groups of clinical manifestations: (1) motor deficits in all patients (4 with
      faciobrachial, 2 with faciobrachiocrural, and 1 with brachiocrural, crural and
      facial paresis each); (2) hypesthesia in 3 patients with partial distribution
      concerning light touching without involvement of other sensory modalities; (3)
      transient speech disturbance at stroke onset in 1 patient and dysarthria in 2
      patients. Small artery disease in 4 patients and artery-to-artery embolism in 3
      patients probably from atherosclerotic carotid artery were the main stroke
      mechanism. CONCLUSIONS: Strokes restricted to the EcC-ExC region may present with
      complete or partial motor syndromes and dysarthria as prominent clinical
      presentations, but also fou rire prodromique and transient speech arrest as
      prodromal signs. The main etiology of stroke were microangiopathy and artery-to
      artery embolism, even though no obvious cause was found in 1 patient. The
      prognosis was good in almost all patients.

PMID- 16446534
TI  - Analysis of emboli during carotid stenting with distal protection device.
AB  - BACKGROUND: The newly developed multi-frequency transcranial Doppler (TCD) is
      able to differentiate gaseous from solid emboli. Our goal was to apply this
      technology to initially characterize emboli detected during carotid stenting with
      distal protection. METHODS: Patients undergoing carotid angiography and stenting
      were monitored with 2-2.5 MHz TCD (Embo-Dop, DWL) over the middle cerebral artery
      unilateral to stent deployment. Sonographers insured optimal signal recordings
      during the procedures. Automated emboli detection and classification software
      (MultiXLab version 2.0) was applied for offline count and analysis. Monitoring
      using the Filter Wire EX (Boston Scientific) and ACCUNET system (Guidant
      Corporation) was performed. RESULTS: A total of 9,649 embolic signals were
      detected during 11 angiographic and 10 stenting procedures. An observer confirmed
      the signals using the International Consensus definition. Automated software
      classified these events into 5,900 gaseous and 3,749 solid emboli. During
      contrast injections without the protection device, 1,013 emboli were detected
      with 28% of these being solid. With deployment of the distal protection device,
      8,636 emboli were found with 40% being solid (p < 0.001). During stenting and
      angioplasty with the protection device, 7,395 emboli with 42% solids were
      detected (p < 0.001). Finally injection of contrast after the procedure, with the
      protection device still deployed, yielded 1,241 emboli with 31% solids (NS). Only
      1 patient developed transient hemiparesthesia during ballooning that reduced the
      flow velocity to zero for 14 s. Neither gaseous nor solid emboli resulted in a
      mean flow velocity decrease or clinical symptoms. CONCLUSIONS: Microembolization
      frequently occurs during stenting even with deployment of the distal protection
      device. More solid emboli are seen during manipulations associated with lesion
      crossing. Although novel TCD methods yield a high frequency of embolic signals,
      further validation of this technique to determine the true nature, size, and
      number of emboli is needed.

PMID- 16446536
TI  - Comparison of secondary prevention care after myocardial infarction and stroke.
AB  - BACKGROUND: Whether secondary prevention of atherosclerosis is performed as
      frequently after cerebrovascular events (stroke or transient ischemic attack) as
      after cardiac events (myocardial infarction or angina) is unknown. METHODS: We
      compared the receipt of six secondary preventive care processes among 943 persons
      with a prior cardiac event to that among 523 persons with a prior cerebrovascular
      event using a representative sample of the US population. RESULTS: The cardiac
      event group had higher rates for three care processes: antithrombotic medication
      use in the past year (83-77%, p = 0.01), ever advised to exercise more (66-52%, p
      < 0.001), and ever advised to eat fewer high-fat or high-cholesterol foods (70
      54%, p < 0.001). CONCLUSIONS: Compared to the cardiac event group, the quality of
      care of the cerebrovascular event group is lower and should be improved.

PMID- 16446535
TI  - Does age predict outcome in stroke rehabilitation? A study of 878 Chinese
      subjects.
AB  - BACKGROUND: The predicting value of age on stroke rehabilitation has been
      controversial. There is a lack of large-scale studies in the Chinese population
      to examine the effect of age on stroke rehabilitation outcomes. This study
      examines the predictors of a good outcome after rehabilitation in Chinese stroke
      patients with special attention to age as a factor. PATIENTS AND METHODS: This
      retrospective cohort study includes stroke patients receiving a standard
      inpatient multidisciplinary rehabilitation program in a neuro-rehabilitation ward
      of a convalescence hospital in Hong Kong from January 2000 to December 2003.
      Functional independence measure (FIM) >or=90 was used to define a good outcome.
      Multivariate regression analysis was used to assess the independent predictors of
      a good outcome. RESULTS: There were important differences in clinical
      characteristics and complications of stroke among patients of three age groups:
      <65, >or=65 and <80, and >or=80 years. The total FIM scores both upon admission
      and at discharge were lower in the older age groups. No significant difference
      was observed in the changes in FIM scores across these age groups. Age was not an
      independent predictor for a good outcome. FIM upon admission was an independent
      predictor for a good outcome (discharge FIM >or=90) in all patients and in
      individual age groups. Having employment before stroke was a predictor for good
      outcome in all patients. Living at home prior to stroke was a predictor for the
      total population and the >or=65 and <80 years group. The length of stay predicted
      a good outcome in the group >or=80 years. CONCLUSIONS: Admission functional
      status, employment and living at home before stroke but not age per se are
      predictors of a good outcome following stroke rehabilitation. As older patients
      show comparable improvement during rehabilitation, intensive rehabilitation
      should not be withheld in stroke patients simply because of advanced age.

PMID- 16446537
TI  - Efficacy of dual antiplatelet therapy in cerebrovascular disease as demonstrated
      by a decline in microembolic signals. A report of eight cases.
AB  - BACKGROUND: The presence of microembolic signals (MES) may indicate an increased
      risk of recurrent ischemic events in patients with stroke. The optimal management
      of such patients is uncertain. We report the effect of clopidogrel in addition to
      aspirin on the number of MES in a series of patients with ischemic stroke and
      transient ischemic attack (TIA) due to large-vessel disease. METHODS: 8 patients
      with either extracranial or intracranial artery stenosis were identified in 30
      min MES studies by transcranial Doppler sonography as having MES. All patients
      were on antiplatelet therapy prior to baseline transcranial Doppler monitoring.
      The patients were subsequently treated with clopidogrel in addition to aspirin.
      Repeat MES studies were performed between day 3 and 7 with aspirin and
      clopidogrel. RESULTS: All patients were Chinese. The median interval time from
      symptom onset to initial MES study was 7 days (range of 2-30). MES donor sites
      included 4 severely stenosed or occluded internal carotid arteries and 4 stenosed
      middle cerebral arteries. The median MES number at baseline was 8 (range 3-51).
      Repeat MES studies showed a significant decrease in MES (p = 0.012, Wilcoxon
      signed ranks test). 4 patients had complete cessation of MES and all patients
      showed a decline in MES. No patient had recurrent strokes or bleeding
      complications. CONCLUSION: The rapid and significant decline of MES in our stroke
      and TIA patients suggests the possible efficacy of dual antiplatelet therapy with
      aspirin and clopidogrel in patients with MES and symptomatic large-artery
      occlusive disease. Randomized controlled trials should be conducted to confirm
      this preliminary observation.

PMID- 16446538
TI  - Spasticity and its association with functioning and health-related quality of
      life 18 months after stroke.
AB  - BACKGROUND: There is no consensus concerning the presence of spasticity or the
      relationship between spasticity and functioning and spasticity and health-related
      quality of life (HRQL) in the stable phase after stroke. OBJECTIVE: The aim of
      the present study was to describe, 18 months after stroke, the frequency of
      spasticity and its association with functioning and HRQL. METHODS: In a cohort of
      66 consecutive patients with first-ever stroke, studied prospectively, the
      following parameters were assessed 18 months after stroke: spasticity, by the
      Modified Ashworth Scale (0-4 points with 1+ as the modification), muscle
      stiffness, by self-report, abnormal tendon reflexes, by physical examination,
      motor performance, by the Lindmark Motor Assessment Scale, mobility, by the
      Rivermead Mobility Index, activities of daily living, by the Barthel Index, and
      HRQL, by the Swedish Short Form 36 Health Survey Questionnaire (SF-36). RESULTS:
      Of 66 patients studied, 38 were hemiparetic; of these, 13 displayed spasticity,
      12 had increased tendon reflexes, and 7 reported muscle stiffness 18 months after
      stroke. Weak (r < 0.5) to moderate (r = 0.5-0.75) correlations were seen between
      spasticity and functioning scores. Correlations between spasticity and HRQL were
      generally weak (r < 0.5). Hemiparetic patients without spasticity had
      significantly better functioning scores and significantly better HRQL on 1 of the
      8 SF-36 health scales (physical functioning) than patients with spasticity.
      CONCLUSIONS: Few patients displayed spasticity 18 months after stroke. Spasticity
      might contribute to impairment of movement function and to limitation of
      activity, but seems to have a less pronounced effect on HRQL.

PMID- 16446539
TI  - Decreased frequencies of ABCA1 polymorphisms R219K and V771M in Hungarian
      patients with cerebrovascular and cardiovascular diseases.
AB  - BACKGROUND AND PURPOSE: Genetic polymorphisms in ABC transporter A1 (ABCA1) may
      alter the regulation of plasma high-density lipoprotein (HDL), promoting or
      protecting from vascular diseases. METHODS: We investigated 244 unrelated,
      consecutively enrolled patients with ischemic stroke, 150 patients with coronary
      heart disease (CHD) and 193 blood donors for allele frequencies (AFs) of three
      common ABCA1 polymorphisms (R219K, V771M and I883M). RESULTS: Compared to
      controls (30.8 +/- 4.7 and 4.9 +/- 2.2%, respectively), decreased AFs were found
      in both patient groups for R219K and V771M (28.7 +/- 4.1 and 3.1 +/- 1.6% in
      stroke, and 25.7 +/- 5.0%; 1.3 +/- 1.3% in CHD patients, respectively). In a
      subset of stroke patients younger than 50, both variants occurred in
      significantly lower frequencies (22.4 +/- 5.5 and 1.8 +/- 1.7%, respectively).
      Similarly, among CHD patients younger than 60, AFs of R219K and V771M (22.6 +/-
      7.5 and 0 +/- 1.6%, respectively) were decreased. V771M was almost exclusively
      (35/36) found in individuals carrying the R219K allele. CONCLUSIONS: Our data
      confirm earlier observations that ABCA1 R219K and V771M polymorphisms may be
      associated with a protective role against CHD and extend those to another
      important pathologic condition, namely stroke.

PMID- 16446540
TI  - Effect of smoking status on outcome after acute ischemic stroke.
AB  - BACKGROUND: The status of smoking as a risk factor for the occurrence of stroke
      is well established. However, there is a paucity of data on the relationship
      between smoking status and acute stroke outcomes. We evaluated the role of recent
      smoking as a prognostic factor following acute ischemic stroke. METHODS: We
      analyzed data from patients enrolled in the Intravenous Magnesium Efficacy in
      Stroke (IMAGES) trial. Outcome measures studied included change in IMAGES stroke
      score, poor functional outcomes at day 30 and 90 (defined as Rankin Scale >1 and
      Barthel Index <95), and survival over the first 3 months after stroke. The
      independent effect of smoking status (subjects who had smoked in the past year)
      on outcome was evaluated by logistic regression analysis and Cox's proportional
      hazards model, adjusting for variables known to predict outcome after ischemic
      stroke. RESULTS: There were 2,386 subjects in the IMAGES efficacy dataset,
      including 615 recent or current smokers and 1,771 nonsmokers, among whom smokers
      were younger (p < 0.0001). After adjusting for covariates, smokers had increased
      odds of poor 90-day functional outcome independently of other statistically
      significant predictor variables, as assessed by Rankin Scale (odds ratio 1.38;
      95% confidence interval 1.09-1.75) and Barthel Index (odds ratio 1.42; 95%
      confidence interval 1.13-1.79) at day 90. Smoking status did not affect survival
      at day 90. CONCLUSIONS: Current or recent smokers experience poorer functional
      outcomes than nonsmokers 3 months after acute ischemic stroke.

PMID- 16446541
TI  - Lack of association of lobar intracerebral hemorrhage with apolipoprotein E
      genotype in an unselected population.
AB  - BACKGROUND: Both the upsilon2 and upsilon4 alleles of the apolipoprotein E gene
      (APOE) have been reported to be overrepresented in lobar intracerebral hemorrhage
      and to be associated with cerebral amyloid angiopathy (CAA). These studies were
      performed primarily on the North American population and investigated in partly
      selected patient cohorts. METHODS: 193 consecutive patients suffering from
      primary intracerebral hemorrhage (ICH) were included in our study. The
      localization of the ICH, i.e. cortico-subcortical, deep white matter, basal
      ganglia, brainstem and cerebellum, was put in relation to the APOE genotype and
      vascular risk factors. In 101 of these patients, the APOE genotype was also
      correlated to the presence and distribution of microbleeds and other
      microangiopathy-related damage, as shown by magnetic resonance imaging (MRI).
      RESULTS: We found neither an association of a specific APOE genotype with ICH
      localization nor with microangiopathy-related MRI findings. CONCLUSIONS: In our
      study of an unselected Central European population, the APOE genotype was not
      confirmed as a candidate for providing additional diagnostic and potentially
      prognostic information in patients with ICH.

PMID- 16446542
TI  - Modified Rankin scale with expanded guidance scheme and interview questionnaire:
      interrater agreement and reproducibility of assessment.
AB  - BACKGROUND: The modified Rankin scale (mRS) is commonly employed as a measure of
      functional outcome after stroke. The purpose of this study was to investigate the
      reliability of the mRS using an expanded guidance scheme and a corresponding
      questionnaire on an unprecedentedly large scale. METHODS: Neurologists
      interviewed patients with cerebral infarction on the basis of the questionnaire.
      These interviews were recorded on videotape. Raters (10 neurologists, 6 nurses
      and 4 physiotherapists) watched the videotapes of 30 patients interviewed and
      assessed the mRS according to the guidance scheme. RESULTS: The agreement between
      the raters, as estimated from the intraclass correlation coefficient, was found
      to be satisfactory with values of 0.947 for neurologists and 0.963 for nurses and
      physiotherapists. The reproducibility was also satisfactory with values of 0.865
      and 0.871, respectively. CONCLUSION: The data obtained suggest that our guidance
      scheme and questionnaire are useful for ensuring the quality of assessments made
      with the mRS.

PMID- 16446543
TI  - Gene-based single nucleotide polymorphisms and linkage disequilibrium patterns of
      29 asthma candidate genes in the chromosome 5q31-33 region in Koreans.
AB  - BACKGROUND AND METHODS: Numerous genetic studies have mapped asthma
      susceptibility genes to a region on chromosome 5q31-33 in several populations.
      This region contains a cluster of cytokines and other immune-related genes
      important in immune response. In the present study, to determine the genetic
      variations and patterns of linkage disequilibrium (LD), we resequenced all the
      exons and promoter regions of the 29 asthma candidate genes in the chromosome
      5q31-33 region. RESULTS: We identified a total of 314 genetic variants, including
      289 single nucleotide polymorphisms (SNPs), 22 insertion/deletion polymorphisms
      and 3 microsatellites. Standardized variance data for allele frequency revealed
      substantial differences in SNP allele frequencies among different ethnic groups.
      Interestingly, significant ethnic differences were observed mainly in intron
      SNPs. LD block analysis using 174 common SNPs with a frequency of >10% disclosed
      strong LD within most candidate genes. No significant LD was observed across
      genes, except for one LD block (CD14-IK block). Gene-based haplotype analyses
      showed that 1-5 haplotype-tagging SNPs may be used to define the six or fewer
      common haplotypes with a frequency of >5%, regardless of the number of SNPs.
      CONCLUSION: Overall, our results provide useful information for the
      identification of immune-mediated disease genes in the chromosome 5q31-33 region,
      as well as valuable evidence for gene-based haplotype analysis in disease
      association studies.

PMID- 16446544
TI  - Levalbuterol inhibits human airway smooth muscle cell proliferation: therapeutic
      implications in the management of asthma.
AB  - BACKGROUND: Racemic albuterol is a mixture of (R)- and (S)-enantiomers of
      albuterol. Its pharmacological activity and clinical efficacy reside in the (R)
      enantiomer (levalbuterol), but the (S)-enantiomer exacerbates airway reactivity
      in nonclinical models. The role of albuterols in airway smooth muscle cell (SMC)
      proliferation is not well understood. METHODS: The effect of levalbuterol on
      human bronchial SMC growth was compared with the effects of racemic albuterol and
      (S)-albuterol. Cells were fed albuterols and 3H-thymidine in 5% FBS and incubated
      for 24 h. The effect of (S)-albuterol on levalbuterol actions was also studied
      and so were the effects of cAMP/PKA, PI-3 kinase, NK-kappaB, and retinoblastoma
      (Rb) proteins on albuterols and human bronchial SMC proliferation. RESULTS:
      Levalbuterol inhibited cell proliferation at low concentrations. The growth
      inhibitory effect of levalbuterol occurs via activation of the cAMP/PKA pathway.
      Addition of (S)-albuterol to levalbuterol decreased the growth-inhibitory effect
      of levalbuterol, and (S)-albuterol attenuated levalbuterol-induced cAMP release
      by 65%. Levalbuterol inhibited NF-kappaB and Rb protein expressions. ICI-118551
      abrogated the inhibitory properties of levalbuterol. The PAF receptor antagonist
      CV-3988 inhibited (S)-albuterol-induced cell growth, with no effect on
      levalbuterol. CONCLUSIONS: Levalbuterol inhibits cell growth by activating the
      cAMP/PKA pathway and inhibiting PI-3 kinase, NF-kappaB and Rb protein expression,
      and (S)-albuterol induces cell growth by activating PAF-receptor-mediated cell
      signaling.

PMID- 16446545
TI  - CD14 promoter polymorphisms in atopic families: implications for modulated
      allergen-specific immunoglobulin E and G1 responses.
AB  - BACKGROUND: CD14 promoter DNA sequence polymorphisms for the endotoxin receptor
      gene have been implicated in modulating allergen-specific immunoglobulin (Ig)E
      responses in randomly selected individuals with atopy. We sought to determine if
      a single nucleotide polymorphism in the CD14 promoter region is associated with
      atopy in atopic families, and to assess its influence on serum levels of CD14 and
      allergen-specific IgE and IgG1 responses. METHODS: We screened 367 members of 91
      Caucasian nuclear families with a history of asthma for pulmonary function by
      spirometry, including methacholine challenge to detect bronchial hyperreactivity,
      and atopy by serum total IgE and skin prick test to 14 allergens. The CD14
      promoter single nucleotide polymorphism was analyzed in DNA isolated from
      peripheral blood mononuclear cells to identify C/C, C/T and T/T genotypes. Serum
      tests were done for soluble CD14 (sCD14) and dust mite-specific antibody (Der p 1
      IgG1). RESULTS: Serum sCD14 levels were not associated with clinical phenotypes
      (asthma, bronchial hyperreactivity or atopy). However, sCD14 levels were
      inversely related to both allergen-specific IgE and Der p 1-IgG1 production, but
      only among those with evidence of atopic sensitization. Linear regression
      analysis, accounting for random family effects, demonstrated a higher production
      of allergen-specific IgE or Der p 1-IgG1 associated with the T/T genotype and a
      lower level of specific IgE and IgG1 production associated with sCD14 levels.
      CONCLUSIONS: An element of the innate immune system (CD14) has profound effects
      upon modulating the acquired allergen-specific immunoglobulin responses among
      those with an inherited atopic predisposition.

PMID- 16446546
TI  - Immunoglobulin E and G4 antibody responses in occupational airway exposure to
      bovine and porcine plasma proteins.
AB  - BACKGROUND: Production of both antigen-specific immunoglobulin (Ig)E and IgG4
      antibodies is dependent on stimulation of B cells by T helper 2 cell-derived
      cytokines. However, there is controversy as to their interaction. In this study,
      we investigated the interdependency of IgE and IgG4 antibody responses to a
      relatively high range of airway exposure to animal-derived proteins in an
      occupational setting. Moreover, associations with self-reported airway symptoms
      and bronchial hyperresponsiveness were established. METHODS: In a cross-sectional
      design, employees of an animal plasma spray-drying factory were questioned about
      airway symptoms, exposure was measured with personal sampling technique, and
      serology was performed. In a selection of subjects from this population, serology
      was repeated 15 months later, and bronchial hyperresponsiveness was measured.
      RESULTS: IgE and IgG4 antibodies were detected in 17 and 57% of all employees and
      were both associated with degree of exposure. Only IgE antibodies showed an
      independent association with self-reported airway symptoms and bronchial
      hyperresponsiveness. The presence of IgE antibodies was limited to employees with
      high levels of IgG4. Employees with IgE and symptoms appeared to have less IgG4
      than asymptomatic IgE-positive individuals. The level of specific IgG4 antibodies
      was stable over a 15-month period. CONCLUSIONS: In high-range airway exposure,
      development of IgE and IgG4 antibodies depended on the level of exposure. The
      threshold for development of IgG4 antibodies appeared to be less than that for
      IgE antibodies, and IgG4 antibodies may protect against the development of
      symptoms.

PMID- 16446547
TI  - Differential protective properties of estradiol and tamoxifen against
      methamphetamine-induced nigrostriatal dopaminergic toxicity in mice.
AB  - Mechanisms implicated in protective potential of estrogens are poorly understood.
      Tamoxifen, a selective estrogen receptor modulator (SERM), presents a
      neuroprotective effect against methamphetamine (MA)- and methoxy
      phenyltetrahydropyridine (MPTP)-induced toxicity when used alone but abolishes
      estrogen's positive effects when combined with this hormone. In order to
      understand tamoxifen's protective properties, the present study compared it to
      estradiol on several markers of dopaminergic neurons to achieve a relatively
      comprehensive comparison between these two agents. Estradiol benzoate (E) or
      tamoxifen were used at different concentrations (E: 1, 10 or 40 microg;
      tamoxifen: 12.5, 125 or 500 microg) 24 h prior to a MA injection in
      ovariectomized CD-1 mice. The effects of the lesion and treatments were studied
      on striatal dopamine (DA) concentrations, dopamine and monoamine vesicular
      transporters (DAT and VMAT2), and preproenkephalin (PPE) mRNA levels. Both
      treatments, at all concentrations, prevented the MA-induced decrease of striatal
      DA concentrations and VMAT2 binding. Only E was able to prevent loss of DAT
      binding in the lateral striatum and to attenuate the MA-induced increase in
      striatal PPE mRNA levels (at 1 or 40 microg). Therefore, in this paradigm, E and
      tamoxifen differentially modulated MA-induced neuronal damages. While both
      treatments prevented the DA decrease, E protected more efficiently other
      dopaminergic parameters suggesting that overall E is more effective than
      tamoxifen as a neuroprotectant of the nigrostriatal dopaminergic system.

PMID- 16446548
TI  - A new specific gene expression in squamous cell carcinoma of the esophagus
      detected using representational difference analysis and cDNA microarray.
AB  - OBJECTIVES: To detect new specific gene expressions in squamous cell carcinoma of
      the esophagus. METHODS: Representational difference analysis of cDNA (cDNA RDA)
      was applied to a human esophageal cancer cell line (KYSE170) and a human
      esophageal epithelial cell line (HEEC-1). RESULTS: LAGE-1 was expressed
      specifically in KYSE170, but not in HEEC-1. It is also expressed in 27% of
      esophageal cancer cell lines (3/11) and 33% of esophageal cancer tissues (10/30),
      but not in other HEECs, normal esophageal epithelium, or other normal tissues
      except testis, ovary and kidney. The expression of LAGE-1 is strongly correlated
      with that of MAGE-A1 (p = 0.013, Fisher's exact probability test). Fibronectin,
      cytokeratin 6B, cytokeratin 19, cyclin D2 and Ten-m2 were detected as candidates
      for downregulated genes. Reduced expression profiles of them were also identified
      using cDNA microarrays. The expression of LAGE-1 was induced by 5'-aza-2'
      deoxycytidine (5Aza-dC) and trichostatin A (TSA) in esophageal cancer cell lines,
      which did not express LAGE-1. In HEECs, 5Aza-dC induced LAGE-1 expression, but
      TSA did not. CONCLUSIONS: LAGE-1 expression was detected in esophageal cancer by
      cDNA RDA. LAGE-1 might have the potential to be a target antigen for anti-tumoral
      immunotherapy in esophageal cancers because of its tumor-specific expression
      similar to that of MAGE-A1.

PMID- 16446549
TI  - Chemotherapy-induced carcinoembryonic antigen surge in patients with metastatic
      colorectal cancer.
AB  - OBJECTIVES: To investigate the incidence of carcinoembryonic antigen (CEA) surge
      in patients with metastatic colorectal cancer (MCRC) and its implications on
      clinical outcome. METHODS: A retrospective chart review of patients with MCRC
      treated with chemotherapy at Roswell Park Cancer Institute from January 2000 to
      May 2004 was conducted. A CEA surge was defined as an increase of >20% from
      baseline followed by a >20% drop in one or more subsequent CEA levels compared to
      baseline. The incidence of CEA surge and its association with clinical outcome
      was investigated. RESULTS: Eighty-nine patients were evaluable for CEA surge. A
      CEA surge was documented in 10 patients. The CEA surge lasted <4 months in all 10
      patients and was associated with a clinical benefit. No significant correlation
      was noted between CEA surge and site of primary tumor, site of metastatic
      disease, or tumor differentiation. CONCLUSIONS: CEA surges can be observed in
      patients receiving chemotherapy for MCRC and are often associated with a clinical
      benefit. None of the CEA surges satisfied the American Society of Clinical
      Oncology definition of CEA progression. A rise in CEA after initiation of
      chemotherapy, unless lasting >4 months, cannot be used as an indicator of
      progressive disease.

PMID- 16446550
TI  - A newly identified MAGE-3-derived, HLA-A24-restricted peptide is naturally
      processed and presented as a CTL epitope on MAGE-3-expressing gastrointestinal
      cancer cells.
AB  - PURPOSE: In order to broaden the possibility for anti-MAGE-3 immune targeting, it
      is important to identify HLA-A24-restricted epitopes derived from MAGE-3, since
      HLA-A24 is one of the most common alleles in Japanese and Asian people. In the
      present study, we defined a new MAGE-3 derived, HLA-A24-binding peptide presented
      as a CTL epitope on gastrointestinal cancer cells. MATERIALS AND METHODS: A panel
      of MAGE-3-derived peptides (9mer and 10mer) with the HLA-A24-binding motif was
      selected, and identification of MAGE-3-derived, HLA-A24-restricted CTL epitopes
      was performed by a reverse immunology approach. To induce MAGE-3-peptide specific
      CTLs, PBMCs were repeatedly stimulated with monocyte-derived, mature DCs pulsed
      with the peptides. Subsequent peptide-induced T cells were tested for their
      specificities by ELISPOT, tetramer and cytotoxic assay. CTL clones were then
      obtained from the CTL line by limiting dilution. RESULTS: The peptide-inducing
      CTLs revealed that MAGE-3(113)-peptide was reacted as a CTL epitope in a HLA-A24
      restricted fashion, confirmed by ELISPOT and cytotoxic assays. In addition, the
      MAGE-3(113)-specific CTL clones, confirmed by tetramer assay, showed that the
      MAGE-3(113) epitope is naturally processed and presented as the CTL epitope on
      MAGE-3-expressing gastrointestinal cancer cells by evaluating the cold target
      inhibition assays. CONCLUSION: The newly identified MAGE-3(113)-peptide epitope
      is naturally processed and presented as the CTL epitope on MAGE-3-expressing
      gastrointestinal cancer cells, indicating that anti-MAGE-3 immune targeting with
      the MAGE-3(113) peptide is a promising approach for treatment.

PMID- 16446551
TI  - A phase II study of infusional 5-fluorouracil and low-dose leucovorin with
      docetaxel for advanced gastric cancer.
AB  - BACKGROUND: The standard chemotherapy regimen for advanced gastric cancer has not
      yet been established. We investigated the efficacy and the safety of the
      combination of docetaxel with infusional 5-fluorouracil (5-FU) and leucovorin
      (FLT) in advanced gastric cancer. METHODS: Patients received docetaxel 75 mg/m(2)
      (1-hour infusion) followed by a leucovorin bolus 20 mg/m(2) and a 24-hour
      infusion of 5-FU 1,000 mg/m(2) (day 1-3) every 3 weeks. The response was
      evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST)
      criteria, and the toxicity was evaluated by National Cancer Institute common
      toxicity criteria (NCI-CTC). RESULTS: Sixty-six patients were enrolled. Median
      relative dose intensity was 86%. Of 57 evaluable patients, the overall response
      rate was 25.7%. The response rate was 34.2% in chemonaive patients and 14.2% in
      the patients who had previously received treatment. Median time to progression
      and overall survival duration were 5.2 and 9.7 months, respectively. The most
      frequent grade 3-4 toxicity was neutropenia, which was the major cause of
      treatment delay. Other hematological and nonhematological toxicities were rare.
      CONCLUSIONS: The FLT regimen showed a comparable efficacy with other second
      generation regimens. Because of the low nonhematological toxicity, this could be
      a potential alternative to the cisplatin-containing regimens in gastric cancer.

PMID- 16446552
TI  - Double-bladed scalpel: a new option for harvesting margins in head and neck
      cancers.
AB  - BACKGROUND: In advanced head and neck tumors margins are very rarely
      comprehensively checked by frozen sections. The goal of this study was to analyze
      a new proposal for harvesting margins using a double-bladed scalpel. METHODS:
      Thirty-eight patients underwent a comprehensive resection of advanced head and
      neck tumors with a double-bladed scalpel. Margins were mapped and checked by
      frozen sections, while tumor resection continued. When positive margins were
      identified, they were excised again, and checked by frozen sections. RESULTS:
      Thirty-three patients (87%) had clear skin and soft tissue margins at frozen
      sections. Five patients (13%) had focal skin and soft tissue-positive margins at
      frozen sections, which were re-excised. Two patients (5%) had skin and soft
      tissue-positive margins only at permanent sections. One was reoperated and 1
      received radiation therapy. The 3-year local control rate was 58%. CONCLUSIONS:
      In this preliminary study, the double-bladed scalpel appeared to be an
      interesting option for complete intraoperative evaluation of surgical margins of
      advanced head and neck tumors.

PMID- 16446553
TI  - Accessory nerve function in lateral selective neck dissection with undissected
      level IIb.
AB  - BACKGROUND: To investigate the accessory nerve function in lateral selective neck
      dissections (LSND) performed in laryngeal squamous cell carcinoma patients
      without dissection of level IIB. METHODS: Fifteen LSND were performed in 11 N0
      laryngeal carcinoma patients with preservation of level IIB. Distal latencies,
      compound muscle action potentials (CMAP), and electromyography findings were
      investigated before surgery, during the 3rd postoperative week, and 3 months
      thereafter to compare the effects of the procedure on the accessory nerve.
      RESULTS: Distal latencies and CMAP values were significantly lower in the early
      and late postoperative periods when compared with preoperative values. In 8
      patients, there was no motor unit potential (MUP) in the early postoperative
      period. However, in the late postoperative period, there was no MUP loss.
      CONCLUSIONS: Only temporary functional deterioration of the accessory nerve was
      seen in patients in whom LSND was performed with undissected level IIB.

PMID- 16446554
TI  - Dexamethasone pharmacokinetics in Guinea pig inner ear perilymph.
AB  - AIM: To study the dexamethasone pharmacokinetics in the inner ear perilymph of
      guinea pigs using high-pressure liquid chromatography. METHODS: Sixty-five guinea
      pigs were divided into three groups. In the first group, the drug application
      protocol used an intra-abdominal dose of 0.5% dexamethasone 4 mg x kg(-1). In the
      second group, an intratympanic application dose of 0.5% dexamethasone 150 microl
      was used. The third group was the control group. The concentrations of
      dexamethasone in inner ear perilymph were determined by high-pressure liquid
      chromatography. RESULTS: The perilymph concentration-time curves of dexamethasone
      conformed to a one-compartment open model after an intra-abdominal application.
      The Cmax was 0.927 +/- 0.008 mg x l(-1), the Tmax 1.47 +/- 0.04 h, the T(1/2K)
      2.92 +/- 0.056 h, the AUC 5.533 +/- 0.05 mg x h x l(-1), the T(1/2Ka) 0.47 +/-
      0.024 h. After an intratympanic application, the perilymph concentration-time
      curves of dexamethasone also conformed to a one-compartment open model. The Cmax
      was 0.201 +/- 0.006 mg x l(-1), the Tmax 0.117 +/- 0.06 h, the AUC 0.868 +/-
      0.004 mg x h x l(-1), the T(1/2K) 2.918 +/- 0.089 h, the T(1/2Ka) 0.161 +/- 0.009
      h. Compared to the intra-abdominal application, the intratympanic application
      resulted in similar levels of inner ear perilymph drug concentrations in 30 min.
      CONCLUSION: Dexamethasone can penetrate the blood-labyrinthine barrier after
      intra-abdominal application. Dexamethasone can enter into perilymph after
      intratympanic application. Under the condition of the study, the intratympanic
      application resulted in a similar level of inner ear perilymph drug
      concentrations compared to the intra-abdominal application in 30 min.

PMID- 16446555
TI  - Is small-fenestra stapedotomy a safer outpatient procedure than total
      stapedectomy?
AB  - We compared two stapedoplasty techniques to evaluate whether one technique is
      safer than the other as an outpatient procedure and to demonstrate possible
      reasons for outpatient failures. We performed a retrospective study of patient
      records of 94 operated adult patients who were all initially scheduled for
      outpatient surgery for otosclerosis (47 total stapedectomies and 47 small
      fenestra stapedotomies). Six patients (13%) with stapedectomy and 1 patient (2%)
      with stapedotomy had to stay overnight at the hospital due to postoperative
      vertigo and nausea. The number of outpatient failures was statistically
      significantly different between the stapedoplasty techniques (p = 0.05). Five
      patients (11%) with stapedectomy and 2 patients (4%) with stapedotomy had a drop
      in bone conduction threshold between 5 and 8 dB pre- to postoperatively (n.s.).
      The short-term hearing improvement did not differ statistically significantly
      between the techniques when compared to the preoperative values. Small-fenestra
      stapedotomy is the safer procedure to be performed as outpatient setting than
      total stapedectomy.

PMID- 16446556
TI  - Suitability of calcium phosphate cement for injection laryngoplasty in rabbits.
AB  - Calcium phosphate cement (CPC) consists of powder and liquid, which become an
      injectable paste after mixing, self-hardening and recrystallizing to calcium
      hydroxylapatite (CaHA) after injection into a living body. In this study, we
      investigated the suitability of CPC as an injectable material for injection
      laryngoplasty using rabbits. All rabbits underwent left recurrent laryngeal nerve
      section and injection laryngoplasty with CPC. At 7 days, scanning electron
      microscopic findings revealed that complete recrystallization from CPC to CaHA
      was achieved in the larynx. At 1, 3, and 6 months, injected CPC stayed in the
      paraglottic space and did not migrate, and the average remaining CPC volume
      percentage was 91.7%. Focal foreign body reaction to injected CPC was almost the
      same as that of autologous fat for all time periods observed. These results
      indicated that CPC appears to be biocompatible, nonabsorbable, nonmigratory, and
      suitable for injection laryngoplasty.

PMID- 16446557
TI  - Evaluation of the mixing point in tinnitus sound therapy by a psychoacoustic
      matching protocol with a digital tinnitus evaluation system.
AB  - Directive counseling and sound therapy have been reported to effectively
      alleviate tinnitus suffering. Without objective evaluation, researchers doubt the
      real effect of sound therapy. This study was designed to evaluate the frequency
      and intensity of the theoretical 'mixing point' (MP) in sound therapy and to
      investigate its relationship with the minimal masking level (MML) of tinnitus.
      The tinnitus tones of 133 patients were successfully matched in frequency
      (dominant in 4-10 kHz) and loudness (83.09 +/- 12.04 dB) using a psychoacoustic
      matching protocol and a newly designed tinnitus evaluation system. The matching
      rate was 83%. The relationship between the MP and MML is described by a linear
      regression equation: MP = 0.90 x MML + 1.98 (r2 = 0.82, p < 0.0001). The results
      of matching and correlation analysis confirmed the consistency of the MP in sound
      therapy. The psychoacoustic characteristics of tinnitus can be objectively
      evaluated with our matching protocol and evaluation system.

PMID- 16446558
TI  - Artificial ear: A training tool for grommet insertion and manual dexterity.
AB  - Under European Working Time Directives, surgical trainees now have to attempt to
      gain adequate operative experience within newly-restricted working hours.
      Surgical skills training must therefore increasingly occur outside theatre and
      away from real patients, in a simulated environment. In ENT, we suggest that
      instruction and practice of grommet insertion may be greatly facilitated through
      the use of an artificial ear model, which can be assembled cheaply and quickly.
      Our 'ear' may also be used for manual dexterity exercises, which have the
      potential to be developed into validated tests of core ENT surgical skills in the
      future.

PMID- 16446559
TI  - Intractable otitis media with eosinophils: Importance of diagnosis and validity
      of treatment for hearing preservation.
AB  - This study investigated hearing levels in cases of intractable otitis media with
      eosinophils and validated the treatment strategy. Medical charts were reviewed
      retrospectively. The diagnosis was made when the proportion of eosinophils in
      middle ear secretions exceeded 10%. Twelve patients were identified and treated
      with an antihistaminergic agent, leukotriene receptor antagonist and topical
      steroid. The air-bone conductance gap decreased significantly with the relief of
      subjective symptoms. Bone conduction hearing levels at 4 and 8 kHz were higher
      than at lower frequencies. There was a significant correlation between subjective
      symptom duration and bone conduction hearing level at 8 kHz, which diminished
      with treatment. Compared with suppurative otitis, active otitis with eosinophilia
      damages high-tone sensory hearing in a time-dependent manner, and antiallergic
      treatment prevents progression of the high-tone sensory hearing loss. We
      emphasize the importance of diagnosis and the validity of treatment for
      intractable otitis media with eosinophils.

PMID- 16446560
TI  - Cannabinoid receptor agonists inhibit Ca(2+) influx to synaptosomes from rat
      brain.
AB  - We examined the effects of cannabinoid receptor agonists on (45)Ca(2+) uptake in
      rat brain synaptosomes. A cannabinoid receptor agonist, (R)-(+)-[2,3-dihydro-5
      methyl-3-[(4-merpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1
      naphthyl)methanone (WIN 55212-2) dose-dependently inhibited (45)Ca(2+) uptake in
      rat synaptosomes. Only an endogenous cannabinoid receptor agonist, anandamide,
      dose-dependently inhibited (45)Ca(2+) uptake in rat synaptosomes, but not an
      endogenous cannabinoid receptor agonist, palmitoylethanolamide. Only a
      cannabinoid CB1 antagonist, [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride] (SR 141716A),
      reversed the inhibitory effect of these WIN 55212-2 and anandamide on (45)Ca(2+)
      uptake in rat synaptosomes, but not a cannabinoid CB2 receptor antagonist, [N
      [(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)
      1-(4-methylbenzyl)pyrazole-3-carboxamide] (SR 144528). The inhibitory effects of
      WIN 55212-2 and anandamide on (45)Ca(2+) uptake in rat synaptosomes were reversed
      by the pretreatment of a voltage-sensitive A-type K(+) channel blocker,
      dendrotoxin, but no other type of K(+) channel blockers, i.e. iberiotoxin,
      charybdotoxin or glibenclamide. These findings suggest that cannabinoid receptors
      inhibit Ca(2+) influx into rat brain nerves via the activation of CB1 receptors
      and the opening of voltage-sensitive A-type K(+) channels.

PMID- 16446561
TI  - The role of oxidative stress in noise-induced hearing loss.
AB  - Modern research has provided new insights into the biological mechanisms of noise
      induced hearing loss, and with these new insights comes hope for possible
      prevention or treatment. Underlying the classic set of cochlear pathologies that
      occur as a result of noise exposure are increased levels of reactive oxygen
      species (ROS) that play a significant role in noise-induced hair cell death. Both
      necrotic and apoptotic cell death have been identified in the cochlea. Included
      in the current review is a brief review of ROS, along with a description of
      sources of cochlear ROS generation and how ROS can damage cochlear tissue. The
      pathways of necrotic and apoptotic cell death are also reviewed. Interventions
      are discussed that target the prevention of noise-induced hair cell death: the
      use of antioxidants to scavenge and eliminate the damaging ROS, pharmacological
      interventions to limit the damage resulting from ROS, and new techniques aimed at
      interrupting the apoptotic biochemical cascade that results in the death of
      irreplaceable hair cells.

PMID- 16446562
TI  - Maturation of auditory steady-state responses in normal babies.
AB  - OBJECTIVE: To track the development of the auditory steady-state response (ASSR)
      through the neonatal and early infant periods in a group of normal-hearing
      babies. DESIGN: This longitudinal study involved assessment at four data
      collection points. ASSR thresholds to modulated 500 Hz and 4 kHz tones were
      established in 20 full-term subjects at 0, 2, 4, and 6 wks of age. RESULTS:
      Significant developmental changes were observed for both test frequencies. Mean
      ASSR threshold levels decreased by approximately 10 dB between the week 0 and
      week 6 data collection points. CONCLUSIONS: The results of this study indicate
      that ASSR threshold levels in normal-hearing neonates and young infants are
      different from those observed in older subjects. Clinical application of the ASSR
      procedure in this population will need to take into account developmental changes
      occurring in the first weeks of life. Furthermore, the findings indicate that
      ASSR thresholds in normal-hearing babies at 6 wks of age are not yet mature.

PMID- 16446563
TI  - Development and evaluation of the listening in spatialized noise test.
AB  - OBJECTIVE: The goal of this study was to design and develop an audiological test
      that provides an ecologically valid measure of speech understanding in background
      noise while minimizing the effects of between-listener variation in factors such
      as linguistic skills and attention on test performance. The Listening in
      Spatialized Noise Test (LISN) creates a three-dimensional auditory environment
      under headphones and was designed to be totally software driven, so that it can
      be delivered in any audiology clinic with the use of only a PC and an audiometer.
      The extent to which the LISN was able to simulate free-field conditions and the
      effect of learning on the test were also examined. DESIGN: : In a three
      alternative forced choice adaptive procedure, 20 adults with normal hearing were
      required to indicate the intelligibility level of target continuous discourse
      presented at 0 degrees azimuth in the presence of distracter sentences
      simultaneously presented at either 0 degrees azimuth (0 degrees condition) or at
      both +90 degrees and -90 degrees azimuth (+/-90 degrees condition). The target
      story was always spoken by female 1, whereas there were three conditions of
      speaker for the distracter sentences: the "same female speaker" as the target
      (same voice condition); two "different female speakers" (different female voices
      condition); and a "male speaker" (male voice condition). In a separate study, 16
      adults with normal hearing who had not participated in the first study were
      assessed on the same voice and different female voices conditions, which were
      presented and then retested in the same order and test session to determine the
      effect of practice on performance on the LISN. RESULTS: The 20 adults were able
      to understand the target story at a significantly lower threshold in the +/-90
      degrees condition than the 0 degrees condition. The degree of this spatial
      separation advantage (SSA) decreased significantly as the vocal quality of
      speakers of the target and the distracter sentences became more different (10.4
      dB in the same voice condition, compared with 5.6 dB in the different female
      voices condition, and only 3.3 dB in the male voice condition). The SSA for the
      different female voices and male voice conditions were comparable to measurements
      previously reported in a free-field environment. There was no significant
      difference in SSA between the first and second presentations for either the same
      voice condition (at 10.3 dB and 10.2 dB) or the different female voices condition
      (at 4.7 and 5.7 dB). CONCLUSIONS: For adults with normal hearing, the ability to
      comprehend the story in the separate condition was facilitated by the use of
      binaural cues, such as interaural time differences, to distinguish the target
      from the spatially separated distracters. When a target and masker are
      distinguishable on the basis of features of the various speakers' voices (such as
      large differences in fundamental frequency), listeners are less reliant on
      spatial cues to recognize the target, and the SSA in dB is reduced. The stability
      of test scores with practice, the comparable levels of performance to those
      achieved in free-field environments, and the ability of the test to utilize
      difference scores to assess binaural processing while minimizing differences
      between participants in variables such as linguistic skills make the LISN a
      potentially valuable tool for assessing auditory processing disorders.

PMID- 16446564
TI  - Bilateral cochlear implants in children: localization acuity measured with
      minimum audible angle.
AB  - OBJECTIVE: To evaluate sound localization acuity in a group of children who
      received bilateral (BI) cochlear implants in sequential procedures and to
      determine the extent to which BI auditory experience affects sound localization
      acuity. In addition, to investigate the extent to which a hearing aid in the
      nonimplanted ear can also provide benefits on this task. DESIGN: Two groups of
      children participated, 13 with BI cochlear implants (cochlear implant + cochlear
      implant), ranging in age from 3 to 16 yrs, and six with a hearing aid in the
      nonimplanted ear (cochlear implant + hearing aid), ages 4 to 14 yrs. Testing was
      conducted in large sound-treated booths with loudspeakers positioned on a
      horizontal arc with a radius of 1.5 m. Stimuli were spondaic words recorded with
      a male voice. Stimulus levels typically averaged 60 dB SPL and were randomly
      roved between 56 and 64 dB SPL (+/-4 dB rove); in a few instances, levels were
      held fixed (60 dB SPL). Testing was conducted by using a "listening game"
      platform via computerized interactive software, and the ability of each child to
      discriminate sounds presented to the right or left was measured for loudspeakers
      subtending various angular separations. Minimum audible angle thresholds were
      measured in the BI (cochlear implant + cochlear implant or cochlear implant +
      hearing aid) listening mode and under monaural conditions. RESULTS: Approximately
      70% (9/13) of children in the cochlear implant + cochlear implant group
      discriminated left/right for source separations of <or=20 degrees , and, of
      those, 77% (7/9) performed better when listening bilaterally than with either
      cochlear implant alone. Several children were also able to perform the task when
      using a single cochlear implant, under some conditions. Minimum audible angle
      thresholds were better in the first cochlear implant than the second cochlear
      implant listening mode for nearly all (8/9) subjects. Repeated testing of a few
      individual subjects over a 2-yr period suggests that robust improvements in
      performance occurred with increased auditory experience. Children who wore
      hearing aids in the nonimplanted ear were at times also able to perform the task.
      Average group performance was worse than that of the children with BI cochlear
      implants when both ears were activated (cochlear implant + hearing aid versus
      cochlear implant + cochlear implant) but not significantly different when
      listening with a single cochlear implant. CONCLUSIONS: Children with sequential
      BI cochlear implants represent a unique population of individuals who have
      undergone variable amounts of auditory deprivation in each ear. Our findings
      suggest that many but not all of these children perform better on measures of
      localization acuity with two cochlear implants compared with one and are better
      at the task than children using the cochlear implant + hearing aid. These results
      must be interpreted with caution, because benefits on other tasks as well as the
      long-term benefits of BI cochlear implants are yet to be fully understood. The
      factors that might contribute to such benefits must be carefully evaluated in
      large populations of children using a variety of measures.

PMID- 16446565
TI  - Using a combination of click- and tone burst-evoked auditory brain stem response
      measurements to estimate pure-tone thresholds.
AB  - DESIGN: A retrospective medical record review of evoked potential and audiometric
      data were used to determine the accuracy with which click-evoked and tone burst
      evoked auditory brain stem response (ABR) thresholds predict pure-tone
      audiometric thresholds. METHODS: The medical records were reviewed of a
      consecutive group of patients who were referred for ABR testing for audiometric
      purposes over the past 4 yrs. ABR thresholds were measured for clicks and for
      several tone bursts, including a single-cycle, Blackman-windowed, 250-Hz tone
      burst, which has a broad spectrum with little energy above 600 Hz. Typically, the
      ABR data were collected because the patients were unable to provide reliable
      estimates of hearing sensitivity, based on behavioral test techniques, due to
      developmental level. Data were included only if subsequently obtained behavioral
      audiometric data were available to which the ABR data could be compared. Almost
      invariably, the behavioral data were collected after the ABR results were
      obtained. Because of this, data were included on only those ears for which middle
      ear tests (tympanometry, otoscopic examination, pure-tone air- and bone
      conduction thresholds) indicated that middle ear status was similar at the times
      of both tests. With these inclusion criteria, data were available on 140 ears of
      77 subjects. RESULTS: Correlation was 0.94 between click-evoked ABR thresholds
      and the average pure-tone threshold at 2 and 4 kHz. Correlations exceeded 0.92
      between ABR thresholds for the 250-Hz tone burst and low-frequency behavioral
      thresholds (250 Hz, 500 Hz, and the average pure-tone thresholds at 250 and 500
      Hz). Similar or higher correlations were observed when ABR thresholds at other
      frequencies were compared with the pure-tone thresholds at corresponding
      frequencies. Differences between ABR and behavioral threshold depended on
      behavioral threshold, with ABR thresholds overestimating behavioral threshold in
      cases of normal hearing and underestimating behavioral threshold in cases of
      hearing loss. CONCLUSIONS: These results suggest that ABR thresholds can be used
      to predict pure-tone behavioral thresholds for a wide range of frequencies.
      Although controversial, the data reviewed in this paper suggest that click-evoked
      ABR thresholds result in reasonable predictions of the average behavioral
      thresholds at 2 and 4 kHz. However, there were cases for which click-evoked ABR
      thresholds underestimated hearing loss at these frequencies. There are several
      other reasons why click-evoked ABR measurements were made, including that they
      (1) generally result in well-formed responses, (2) assist in determining whether
      auditory neuropathy exists, and (3) can be obtained in a relatively brief amount
      of time. Low-frequency thresholds were predicted well by ABR thresholds to a
      single-cycle, 250-Hz tone burst. In combination, click-evoked and low-frequency
      tone burst-evoked ABR threshold measurements might be used to quickly provide
      important clinical information for both ends of the audiogram. These measurements
      could be supplemented by ABR threshold measurements at other frequencies, if time
      permits. However, it may be possible to plan initial intervention strategies
      based on data for these two stimuli.

PMID- 16446567
TI  - The effect of noise on cochlear aging.

PMID- 16446566
TI  - Standard and multifrequency tympanometric norms for Caucasian and Chinese young
      adults.
AB  - OBJECTIVE: This study examined differences between a group of normal-hearing
      Caucasian and Chinese young adults on six tympanometric parameters. The goal of
      this study was to determine if the Chinese group had different low and
      multifrequency tympanometry results than the Caucasian group. DESIGN: There were
      a total of 159 subjects (303 ears) between the ages of 18 and 34 years, with 76
      subjects in the Caucasian group and 83 subjects in the Chinese group.
      Tympanometric data were gathered on a clinical immittance machine, the Virtual
      310 equipped with a high frequency option. Four of the parameters-static
      admittance (SA), tympanometric width (TW), tympanometric peak pressure (TPP), and
      ear-canal volume (ECV)-were measured automatically at a standard 226 Hz
      frequency. The remaining two parameters-resonant frequency (RF) and SA up to
      1,200 Hz-were measured by multifrequency, multicomponent tympanometry, using a
      mathematical approach. RESULTS: The Chinese group had significantly lower SA,
      wider TW, more positive TPP, and lower ECV than their Caucasian counterparts. The
      parameter of SA up to 1,200 Hz showed a significant group effect (Caucasian
      versus Chinese) until 900 Hz in the male group and up to 1,120 Hz in the female
      group. The Chinese group had significantly higher RF than the Caucasian group.
      Once the effect of body size was compensated by adjusting for the ear canal and
      the middle ear volumes, the differences observed between the Caucasian and the
      Chinese groups were no longer significant for tympanometric parameters obtained
      at standard probe tone frequency of 226 Hz; however, the effect was still
      significant for SA obtained at higher probe tone frequencies (560, 630, 710, 800,
      and 900 Hz) and for RF. Applying the Caucasian norms to a group of mainly
      Caucasian adults with surgically confirmed otosclerosis resulted in improved
      overall test performance when compared with the combined Caucasian and Chinese
      norms and the Chinese only norms. CONCLUSIONS: It seems that the body size plays
      a crucial factor in the observed differences between the Caucasian group and
      Chinese groups at a standard probe tone frequency of 226 Hz; however, other
      mechano-acoustical properties of the middle ear may contribute to these
      differences at higher probe tone frequencies. Findings of this study suggest that
      further research is needed to investigate the effects of body size on immittance
      measures with other ethnic groups. In the meantime, overall test performance may
      be improved by using a more homogenous norm when testing the Caucasian or Chinese
      individuals.

PMID- 16446587
TI  - Case reports: Osteogenic sarcoma of the patella spread to lateral meniscus after
      arthroscopy.
AB  - Our patient presented with a rare lesion, a patella osteogenic sarcoma that
      spread to the anterior horn of the lateral meniscus via the arthroscope. He was
      treated arthroscopically for a torn medial meniscus of his right knee. A lesion
      in the patella was observed and a biopsy specimen was obtained through the
      arthroscope. The specimen was diagnosed as an osteogenic sarcoma. After 2 weeks
      of neoadjuvant chemo-therapy, the patient refused additional chemotherapy. Re
      section of the knee and allograft arthrodesis were done 4 months after the
      initial arthroscopy. Pathologic examination of the resected specimen showed
      osteogenic sarcoma of the patella and a completely separate 1.0-cm nodule of
      osteogenic sarcoma tissue growing in the anterior horn of the lateral meniscus.
      The patient died 15 months after knee re-section with multiple pulmonary
      metastases. We are unaware that such an occurrence of an osteosarcoma spread
      through an arthroscope has been documented pathologically and reported.

PMID- 16446588
TI  - Chiropractic: history and overview of theories and methods.
AB  - Chiropractic is one of the most controversial and poorly defined healthcare
      professions with recognition and licensure in the United States. Chiropractic was
      started by D. D. Palmer, a magnetic healer who formulated the vertebral
      subluxation theory. The profession was developed by his son, B. J. Palmer.
      Although the definition of chiropractic as a method of correcting vertebral
      subluxations to restore and maintain health is questionable, spinal manipulation
      is of value in the treatment of some types of back pain. The chiropractic
      profession is still based on the vertebral subluxation theory, and has the
      confusing image of a back specialty capable of treating a broad scope of health
      problems. Despite opposition to use of spinal manipulation as a method of
      treating a broad scope of health problems (as opposed to the generally accepted
      use of manipulation in the treatment of back pain), chiropractors seek support as
      primary care providers in alternative medicine. It is essential to understand the
      theories, philosophies, and methods of chiropractic for an objective evaluation.

PMID- 16446589
TI  - Computer-assisted total knee arthroplasty using patient-specific templating.
AB  - Current techniques used for total knee arthroplasty rely on conventional
      instrumentation that violates the intramedullary canals. Accuracy of the
      instrumentation is questionable, and assembly and disposal of the numerous pieces
      is time consuming. Navigation techniques are more accurate, but their broad
      application is limited by cost and complexity. We aimed to prove a new concept of
      computer-assisted preoperative planning to provide patient-specific templates
      that can replace conventional instruments. Computed tomography-based planning was
      used to design two virtual templates. Using rapid prototyping technology, virtual
      templates were transferred into physical templates (cutting blocks) with surfaces
      that matched the distal femur and proximal tibia. We performed 45 total knee
      arthroplasties on 16 cadaveric and 29 plastic knees, including a comparative
      trial against conventional instrumentations. All operations were performed using
      patient-specific templates with no conventional instrumentations, intramedullary
      perforation, tracking, or registration. The mean time for bone cutting was 9
      minutes with a surgical assistant and 11 minutes without an assistant. Computer
      assisted analyses of six random computed tomography scans showed mean errors for
      alignment and bone resection within 1.7 degrees and 0.8 mm (maximum, 2.3 degrees
      and 1.2 mm, respectively). Patient-specific templates are a practical alternative
      to conventional instrumentations, but additional clinical validation is required
      before clinical use.

PMID- 16446591
TI  - Outcome of partial medial epicondylectomy for cubital tunnel syndrome.
AB  - Partial medial epicondylectomy aims to eliminate potential drawbacks of total
      epicondylectomy for treatment of cubital tunnel syndrome. In this series, we
      retrospectively evaluated 80 patients (80 elbows) who had partial medial
      epicondylectomies for established cubital tunnel syndrome. Our main purpose was
      to compare clinical outcomes among partial, minimal, and total epicondylectomies.
      Specific attention was given to the functional outcome in severely impaired
      patients, and potential postoperative complications of total epicondylectomy,
      such as elbow instability, and medial elbow pain. Preoperatively, 16 patients
      were classified as having McGowan Grade I lesions, 40 had Grade II lesions, and
      24 had Grade III lesions. The mean followup was 32 months (range, 26 months-4.2
      years). There was improvement of at least one McGowan grade in 86.2% of the
      patients, with a 66.7% improvement in severely impaired patients (McGowan Grade
      III lesions). There was no ulnar nerve palsy, no ulnar nerve subluxation, or
      medial elbow instability. However, 45% of patients reported mild pain at the 6
      month followup. Partial medial epicondylectomy seems to be safe and reliable for
      treatment of cubital compression neuropathy at the elbow. LEVEL OF EVIDENCE:
      Therapeutic study, Level IV (case series). See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 16446592
TI  - Clinical features and surgical outcomes of cervical myelopathy in the elderly.
AB  - Treatment of cervical myelopathy in elderly patients is controversial. We
      retrospectively studied 113 patients who had decompression surgery from 1990-2001
      to clarify how pre-operative conditions, duration of symptoms, involved levels,
      surgical outcomes, and complications differ between younger and elderly patients.
      We also asked whether elderly patients would likely have reasonable outcomes of
      surgery. The patients were divided into five age groups: Group 1, 36-45 years (12
      patients); Group 2, 46-55 years (22 patients); Group 3, 56-65 years (31
      patients); Group 4, 66-75 years (32 patients); and Group 5, 76-85 years (16
      patients). The duration of symptoms was similar among the five groups. The
      involved level was more cephalic in the older groups, and the most frequently
      involved level in patients older than 75 years was C3-C4. Neurologic symptoms
      were more severe preoperatively and postoperatively in older patients. The
      recovery ratio also was lower in older patients; however, in Group 5 it was
      36.9%, which indicated that patients older than 75 years could regain
      approximately 40% of their function postoperatively. Decompression surgery can be
      a reasonable treatment option for cervical myelopathy, even in elderly patients.
      LEVEL OF EVIDENCE: Therapeutic Study, Level IV (case series). See the Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 16446593
TI  - Venous thromboembolism is rare with a multimodal prophylaxis protocol after total
      hip arthroplasty.
AB  - We evaluated the safety and efficacy of a multimodal approach for prophylaxis of
      thromboembolism after total hip arthroplasty, which includes preoperative
      discontinuation of procoagulant medication; autologous blood donation;
      hypotensive epidural anesthesia; intravenous administration of heparin during
      surgery and before femoral preparation; aspiration of intramedullary contents;
      pneumatic compression; knee-high elastic stockings; and early mobilization and
      chemoprophylaxis for 4 to 6 weeks (aspirin 83%; warfarin 17%). One thousand nine
      hundred forty-seven consecutive, nonselected patients (2032 total hip
      arthroplasties) who received this multimodal prophylaxis were observed
      prospectively for 3 months. The incidence of asymptomatic deep vein thrombosis
      assessed by ultrasound in the first 171 patients was 6.4%. The incidence of
      clinical deep vein thrombosis in the subsequent 1776 patients was 2.5%.
      Symptomatic pulmonary embolism occurred in 0.6% (12 of 1947; nine in patients
      receiving aspirin and three in patients receiving Coumadin), none of them fatal.
      One patient died of a myocardial infarct. This multimodal approach is safe and
      efficacious and compares favorably with those reported in the literature and with
      our historic controls. If these preventive measures are strictly observed during
      the perioperative period, postoperative chemoprophylaxis does not need to be
      aggressive in the patient without predisposing factors. Our low rate of deep vein
      thrombosis and pulmonary embolism do not support routine anticoagulation
      prophylaxis with drugs that increase risk of bleeding. LEVEL OF EVIDENCE:
      Therapeutic study, Level IV (case series). See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 16446594
TI  - Case reports: acral myxoinflammatory fibroblastic sarcoma: a report of five cases
      and literature review.
AB  - During the past 2 years, we treated five patients with acral myxoinflammatory
      fibroblastic sarcoma at our institution. Four patients presented with a firm,
      painless mass in the hand that appeared over several months. One patient
      discovered a painless mass in his shoulder region. The five patients initially
      were diagnosed as having benign conditions and treated with intralesional or
      marginal excision by referring physicians, only to have the lesion reappear as
      sarcoma. Each patient was treated with wide resection of the tumor bed. Acral
      myxoinflammatory fibroblastic sarcoma is a rare, but increasingly recognized
      sarcoma of the distal extremities, which often is confused with benign lesions.
      Surgeons should be familiar with this tumor's clinical, radiographic, and
      histologic appearances as it has a high rate of recurrence and can metastasize.

PMID- 16446596
TI  - Alendronate in bone cement: fatigue life degraded by liquid, not by powder.
AB  - Bisphosphonates have the potential to reduce osteolysis, a phenomenon that has
      been postulated to play a key role in aseptic loosening of total joint
      replacements. Bisphosphonates may contribute to the in vivo longevity of total
      joint replacements. Some authors have suggested there are decreases in flexural
      strength and flexural modulus of the cured cement when a liquid form of disodium
      pamidronate is added to a commercially available acrylic bone cement (Palacos R).
      We proposed that it is comparatively easier to blend a bisphosphonate in powder
      form into an acrylic bone cement than it is when the drug is in liquid form; and
      that the cement's fatigue life is decreased when the bisphosphonate is added in
      liquid rather than in solid form. The bisphosphonate and bone cement used were
      alendronate sodium and Cemex XL, respectively. The fatigue tests were done using
      phosphate buffered saline solution at 37 degrees +/- 1 degrees C. The data
      supported both hypotheses. Our findings should guide orthopaedic surgeons when
      using bisphosphonate-impregnated acrylic bone cements in total joint
      replacements. Bisphosphonates are endogenous pyrophosphate analogs in which a
      carbon atom replaces the central oxygen atom. These therapeutic agents may be
      classified into nitrogen and non-nitrogen containing types. Some examples are
      alendronate, pamidronate, ibandronate, risedronate, etidronate, clodronate, and
      zoledronate. There are many targets and mechanisms of action of this family of
      drugs, therefore making them efficacious against diverse clinical conditions such
      as osteoporosis, periprosthetic bone loss subsequent to total joint replacement,
      tumor cell proliferation, apoptosis and angiogenesis, Charcot neuroarthropathy,
      rheumatoid arthritis, ankylosing spondylitis and spondyloarthropathies, and
      arterial calcification. It has been proposed that some bisphosphonates are
      effective against the mechanisms that have been suggested as being implicated in
      aseptic loosening of total joint replacements, these being osteoclast-mediated
      bone resorption and wear particle-induced osteolysis. A meta-analysis of
      randomized controlled trials showed that alendronate and pamidronate had
      beneficial effects maintaining periprosthetic bone for as much as 1 year after a
      total joint replacement.

PMID- 16446597
TI  - Cerebral oxygenation in neonatal and pediatric patients during veno-arterial
      extracorporeal life support.
AB  - OBJECTIVE: To observe the effects of right carotid artery ligation and variations
      in extracorporeal life support (ECLS) flow on regional cerebral oxygenation index
      (rSO2i) measured using near infrared spectroscopy. DESIGN: Prospective
      observational study. SETTING: Tertiary children's hospital. PATIENTS: Eleven
      neonatal and pediatric patients requiring veno-arterial ECLS support between June
      2000 and March 2003. INTERVENTIONS: Near infrared spectroscopy probe placement on
      left and right frontal regions of patients undergoing ECLS, before vessel
      cannulation or within 24 hrs of initiation of ECLS. MEASUREMENTS AND MAIN
      RESULTS: Regional cerebral oxygenation was measured every minute for 72 hrs or
      until the patient was decannulated. The effect of cannulation on rSO2i from each
      hemisphere of the brain and the relationship between ECLS flow and rSO2i during
      ECLS support and "trialing off" periods were determined. Ligation of the right
      carotid artery resulted in a 12-25% decrease in rSO2i from baseline in the right
      frontal region for a duration ranging from 17 to 45 mins before returning toward
      baseline. No substantial change in the left frontal region rSO2i was detected
      during cannulation. Following this depression in rSO2i on the right, there was a
      transient increase above baseline in rSO2i observed in both hemispheres on
      initiating ECLS. No correlation between ECLS flow and rSO2i was found over the 72
      hr period. Periods of "trialing off" ECLS were not related to any change in rSO2i
      in either hemisphere. CONCLUSIONS: This study demonstrated no relationship
      between ECLS flow and rSO2i changes during the 72-hr observation period. A brief
      period of cerebral oxygen desaturation of the right frontal region at the time of
      right carotid ligation was seen in all three study patients examined during
      cannulation, followed by an increased rSO2i with initiation of ECLS flow. Near
      infrared spectroscopy measurement may offer an important adjunct for neurologic
      monitoring of ECLS patients.

PMID- 16446598
TI  - Abdominal compartment syndrome contributing to failure of extracorporeal membrane
      oxygenation in an infant with congenital heart disease and sepsis.
AB  - OBJECTIVE: To provide the first account of extracorporeal membrane oxygenation
      therapy failure secondary to abdominal compartment syndrome. DESIGN: Case report.
      SETTING: Pediatric intensive care unit. PATIENT: A 4-month-old infant with
      cyanotic congenital heart disease and Escherichia coli sepsis developed abdominal
      distention and venous return failure on extracorporeal membrane oxygenation.
      INTERVENTION: Emergency cardiac catheterization and atrial septectomy were
      performed. MAIN RESULTS: Central venous pressure of 120 mm Hg was measured,
      confirming the diagnosis of abdominal compartment syndrome. CONCLUSIONS:
      Abdominal compartment syndrome is a life-threatening condition resulting from an
      increase in intra-abdominal pressure that compromises abdominal organ perfusion,
      pulmonary function, and cardiac output. Mortality rates from abdominal
      compartment syndrome are as high as 60% in adults and children. This report of an
      infant with congenital heart disease and E. coli sepsis represents the first
      description of abdominal compartment syndrome that contributed to failure of
      extracorporeal membrane oxygenation and ultimately death. The pathophysiology,
      diagnosis, and treatment of abdominal compartment syndrome are also reviewed.

PMID- 16446599
TI  - Use of dexmedetomidine in children after cardiac and thoracic surgery.
AB  - OBJECTIVE: In this report, we describe our experience with the use of
      dexmedetomidine in spontaneously breathing as well as in mechanically ventilated
      patients, after congenital cardiac and thoracic surgery. DESIGN: Retrospective
      case series. SETTING: University hospital, pediatric cardiac intensive care unit.
      PATIENTS: Thirty-three spontaneously breathing and five mechanically ventilated
      patients who received dexmedetomidine after cardiothoracic surgery.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients, age 8
      +/- 1.1 yrs old and weight 29 +/- 3.8 kg, were included. Seven patients (18%)
      were <1 yr old. Dexmedetomidine was used as a primary sedative and analgesic
      agent, and when its effect was considered inadequate, despite incremental
      infusion doses, a rescue agent was administered. The initial dexmedetomidine
      infusion dose was 0.32 +/- 0.15 microg/kg/hr followed by an average infusion of
      0.3 +/- 0.05 microg/kg/hr (range 0.1-0.75 microg/kg/hr). There was a trend toward
      higher dexmedetomidine infusion requirement in patients <1 yr old compared with
      older children, 0.4 +/- 0.13 vs. 0.29 +/- 0.17 microg/kg/hr (p = .06). Desired
      sedation and analgesia were achieved during 93% and 83% of the dexmedetomidine
      infusion, respectively. According to the intensive care unit sedation scale
      (score 0-3) and two pain scales (Numeric Visual Analog Scale and Face, Legs,
      Activity, Cry, and Consolability, score 0-10), the mean sedation score was 1.3 +/
      0.6 (mild sedation) and the mean pain score was 1.5 +/- 0.9 (mild pain). The
      most frequently rescue drugs administered were fentanyl, morphine, and midazolam.
      Overall, 49 rescue doses of sedatives/analgesics were given. Patients <1 yr old
      required more rescue boluses than older children, 22 boluses (3.19 +/- 0.8) vs.
      27 boluses (0.8 +/- 0.2, p = .003). Throughout the dexmedetomidine infusion there
      was no significant change in the systolic and diastolic blood pressure trend. Six
      patients (15%) had documented hypotension. In three, hypotension resolved with
      decreasing the dexmedetomidine infusion dose whereas in the other three,
      hypotension resolved after discontinuing the infusion. Although there was a trend
      toward lower heart rates, this was not clinically significant. One patient had an
      episode of considerable bradycardia without hypotension, which resolved shortly
      after discontinuing the dexmedetomidine infusion. No significant changes in the
      arterial blood gases or respiratory rates were observed. There was no mortality,
      and the total intensive care unit length of stay was 19 +/- 2 hrs. CONCLUSIONS:
      Our data suggest that dexmedetomidine is a well-tolerated and effective agent for
      both spontaneously breathing and mechanically ventilated patients following
      congenital cardiac and thoracic surgery.

PMID- 16446600
TI  - Pulmonary edema in meningococcal septicemia associated with reduced epithelial
      chloride transport.
AB  - OBJECTIVES: To test the hypothesis that meningococcal septicemia-related
      pulmonary edema is associated with a systemic abnormality of epithelial sodium
      and chloride transport and to investigate an association with hormones regulating
      Na transport. DESIGN: Prospective observational study. SETTING: The 24-bed
      pediatric intensive care unit and pediatric wards of Royal Liverpool Children's
      Hospital. PATIENTS: Consecutive children admitted to the pediatric intensive care
      unit and pediatric wards with a diagnosis of meningococcal septicemia and
      children (controls) with noninfectious critical illness receiving ventilatory
      support in the pediatric intensive care unit. MEASUREMENTS AND MAIN RESULTS: We
      measured sweat and saliva electrolytes, renal electrolyte excretion, nasal
      potential difference, and aldosterone, thyroxine, and cortisol levels. Pulmonary
      edema was diagnosed by chest radiography and its severity quantified by
      calculation of ventilation index at admission and duration of mechanical
      ventilation. We recruited 17 patients with severe meningococcal septicemia (nine
      patients with pulmonary edema), 14 patients with mild meningococcal septicemia,
      and 20 controls. Sweat and saliva Na and Cl concentrations and renal Na excretion
      were significantly (p < .05) higher in patients with pulmonary edema compared
      with controls. Nasal potential difference and amiloride response in patients with
      pulmonary edema were not significantly different to controls, but response to a
      low Cl solution was reduced in the nasal airway of patients with pulmonary edema
      (p < .05). Sweat and saliva chloride concentrations correlated significantly and
      better with ventilation index and duration of ventilation than sodium
      concentrations. Aldosterone, thyroxine, and cortisol levels were not
      significantly different between groups. CONCLUSIONS: We have confirmed that
      meningococcal septicemia-related pulmonary edema is associated with reduced
      systemic sodium and chloride transport. Features of reduced Cl transport were
      most closely associated with markers of respiratory compromise, and this was
      supported by the reduced chloride channel function detected on nasal potential
      difference measurement.

PMID- 16446602
TI  - Dopamine is not an independent risk factor for reduced amikacin clearance in
      extremely low-birth-weight infants.
AB  - INTRODUCTION: Important inter-individual variability in amikacin clearance was
      observed in preterm infants, only in part explained by gestational age (GA),
      birth weight, or coadministration of nonselective cyclo-oxygenase (COX)
      inhibitor. We therefore evaluated whether dopamine had an additional effect on
      amikacin clearance. METHODS: Clinical characteristics (GA, weight, COX inhibitor,
      dopamine, prenatal betamethasone) and amikacin pharmacokinetics were
      retrospectively collected in a cohort of preterm infants (GA of <31 wks, early
      neonatal life on respiratory support, between January 1, 1999 and January 6,
      2005). Pharmacokinetics were calculated by assuming a one-compartment model with
      instantaneous input and first-order output based on paired samples collected for
      therapeutic drug monitoring before and following second administration.
      Monovariate analysis (Spearman, Mann-Whitney U test) was used to study the impact
      of clinical characteristics on amikacin clearance, and logistic regression was
      used to assess their potential independent effect. RESULTS: Paired amikacin
      samples were available for 240 neonates (mean GA, 28 wks; birth weight, 1042 g).
      Amikacin clearance was 0.46 (range, 0.09-2.33) mL/kg/min and distribution volume
      was 0.54 (range, 0.17-2.31) L/kg. GA, birth weight, COX inhibitor, and dopamine
      had a significant effect on amikacin clearance. In a logistic regression model,
      dopamine was no longer a significant variable when GA, birth weight, or
      cotreatment of a nonselective COX inhibitor was entered as second variable.
      CONCLUSIONS: Dopamine is an indicator but not an independent marker of reduced
      amikacin clearance in early neonatal life in extremely low-birth-weight infants.
      Therefore, neither dose nor interval should be adapted when dopamine is
      prescribed, if GA and coadministration of nonselective COX inhibitors already
      have been taken into account.

PMID- 16446601
TI  - State Behavioral Scale: a sedation assessment instrument for infants and young
      children supported on mechanical ventilation.
AB  - OBJECTIVE: To develop and test the reliability and validity of the State
      Behavioral Scale for use in describing sedation/agitation levels in young
      intubated patients supported on mechanical ventilation. DESIGN: : In this
      prospective, psychometric evaluation, pairs of trained pediatric critical care
      nurse evaluators simultaneously and independently assessed a convenience sample
      of pediatric intensive care unit patients along eight state/behavioral dimensions
      and a numeric rating scale (NRS) of 0 (extremely sedated) to 10 (extremely
      agitated). The eight dimensions were derived from the sedation/agitation
      literature and expert opinion and included respiratory drive, response to
      ventilation, coughing, best response to stimulation, attentiveness to
      careprovider, tolerance to care, consolability, and movement after consoled, each
      with 3-5 levels. SETTING: An 18-bed pediatric medical-surgical intensive care
      unit and 26-bed pediatric cardiovascular intensive care unit in a university
      affiliated academic children's hospital. PATIENTS: A total of 91 intubated
      mechanically ventilated patients 6 wks to 6 yrs of age provided a median of two
      observations (interquartile range, 1-3) for a total of 198 sets of observations.
      Excluded were postoperative patients or those receiving neuromuscular blockade.
      INTERVENTIONS: Patients were observed for 1 min, and then incremental levels of
      stimulation were applied until patient response. After 2 mins of consoling, the
      state behavioral assessment and NRS were completed. MEASUREMENTS: Weighted kappa
      and intraclass coefficients were generated to assess interrater reliability of
      the eight dimension and NRS ratings. Distinct state behavior profiles were
      empirically identified from the dimension ratings using hierarchical cluster
      analysis using a squared Euclidean distance measure and between-groups linkage.
      Construct validity of these profiles was assessed by comparing group mean NRS
      scores using one-way analysis of variance. MAIN RESULTS: Weighted kappa scores
      for all 198 dimension ratings ranged from .44 to .76, indicating moderate to good
      interrater reliability. The intraclass coefficient of .79 was high for NRS
      ratings. Cluster analysis revealed five distinct state profiles, with mean NRS
      ratings of 1.1, 2.5, 4.0, 5.3, and 7.6, all of which differed significantly from
      each other (F = 75.8, p < .001), supporting the profiles' construct validity.
      CONCLUSIONS: Based on empirically derived state behavior profiles, we have
      constructed the State Behavioral Scale to allow systematic description of the
      sedation-agitation continuum in young pediatric patients supported on mechanical
      ventilation. Further studies including prospective validation and describing the
      effect of State Behavioral Scale implementation on clinical outcomes, including
      the quality of sedation and length of mechanical ventilation, are warranted.

PMID- 16446603
TI  - Internal pancreatic fistula in a child with pancreas divisum: An unusual
      manifestation of an uncommon anomaly.
AB  - OBJECTIVES: Report of an unusual case of pancreatic fistula in a child.
      BACKGROUND: Pancreatic diseases are relatively uncommon in the pediatric age
      group, with a rather heterogeneous clinical picture from generic abdominal
      distension to massive pleural effusion. CLINICAL RELEVANCE: The amylase analysis
      of pleural liquid is crucial for the etiologic diagnosis of pancreatitis with
      internal pancreatic fistula. Magnetic resonance cholangiopancreatography may
      support the etiologic diagnosis of pancreatic pleural fistula in children.
      Management of internal pancreatic fistula is analyzed. CONCLUSION: Maintaining a
      high index of suspicion is essential for the etiologic diagnosis of pancreatic
      pleural fistula in children.

PMID- 16446604
TI  - [Strengthening the College's journal in 2006].

PMID- 16446605
TI  - [Prevention of fetomaternal anti-D alloimmunization: should should noninvasive
      fetal genotyping be instituted now?].

PMID- 16446606
TI  - [Subtotal hysterectomy: evolving concepts with implications for practice].
AB  - INTRODUCTION: The advantages and drawbacks of total and sub-total hysterectomy
      remain a topic of debate. Our study reviews the literature concerning recent
      comparative and prospective studies regarding the options of total and subtotal
      hysterectomy. RESULTS: Subtotal hysterectomy may be useful in preventing severe
      complications when total hysterectomy is technically difficult. Furthermore,
      conservation of the uterine cervix may decrease vaginal erosion in genital
      prolapse repair when synthetic meshes are used. The type of technique does not
      appear to determine the persistence or development of problems related to sexual
      activity (frequency of intercourse, sexual desire, and achievement of orgasm).
      There are no apparent advantages to subtotal hysterectomy compared with total
      hysterectomy with respect to bowel or bladder function. Some women (5-20%) who
      had the subtotal procedure continued to have genital bleeding, although this can
      be avoided with endocervical electro-coagulation or resection. Cervical stump
      prolapse is uncommon (1.5-2%), 12 months after subtotal hysterectomy. The risk of
      carcinoma of the cervical stump is low, and treatment results are similar in both
      patients with carcinoma of the cervical stump and in patients with carcinoma of
      the intact uterus. CONCLUSION: When subtotal hysterectomy is necessary, it can be
      performed with a low rate of long term complications. Furthermore, for women
      undergoing hysterectomy for benign disease, it should be reasonable to discuss
      advantages and drawbacks of both procedures and offer a choice. Nevertheless, sub
      total hysterectomy should be avoided in populations with restricted access to
      screening programs for cancer of the uterine cervix.

PMID- 16446607
TI  - [Follow-up of 70 patients with advanced ovarian cancer after negative second-look
      laparotomy].
AB  - OBJECTIVES: To analyze the results of treatment of 70 patients with stage III and
      IV ovarian cancer after second look laparotomy with negative findings and to
      identify causes of failure and prognostic factors. MATERIALS AND METHODS: Between
      1985 and 1998, seventy patients with ovarian cancer stage III and IV were treated
      with surgery and at least six courses of chemotherapy with cisplatin doxarubicin
      and cyclophosphamide. Then a second look laparotomy was performed. RESULTS: The
      actuarial survival rate without evidence of disease was 50% at 5 years.
      Locoregional failure was observed in 31 patients (88%) and distant metastases in
      9, but they were the sole reason for unsuccessful treatment in only 4 (12%).
      Adverse prognostic factors were: grade 3 differentiation, primary stage IIIC and
      IV, and residual infiltration exceeding 2 cm after first laparotomy. CONCLUSION:
      Our results are comparable with reports in the literature. The actuarial survival
      rate without evidence of disease at 5 years in patients with advanced ovarian
      cancer after second look negative laparotomy is 50%.

PMID- 16446608
TI  - [Neoadjuvant radiochemotherapy and surgery of locally advanced cervical
      carcinoma: review of 22 patients treated at the Bordet Institute].
AB  - OBJECTIVES: Concomitant chemoradiation is the "new gold standard" for dealing
      with locally advanced cervical carcinoma, but what about surgery? We don't know
      yet to what extent surgery is necessary and how radical it must be when it is
      performed. In this study, we present the analysis of the results obtained in
      patients treated by concomitant chemoradiation followed by radical surgery.
      MATERIALS AND METHODS: Twenty-two patients, median age 49 years, with I(b) -
      III(a) cervical tumors were enrolled to be treated by concomitant chemoradiation
      followed by radical surgery. The chemoradiation protocol included external
      radiotherapy to the pelvis: 45 Gy; Cisplatin 40 mg/m(2) in continuous intravenous
      infusion once a week (5 weeks) followed by brachytherapy one week later. Surgery
      was performed 4 to 6 weeks later and consisted in radical hysterectomy with
      pelvic lymphadenectomy. RESULTS: 20/22 patients underwent surgery after
      chemoradiation because of a diagnosis of lung metastases in one and presence of a
      nonresectable metastasis for the other. A complete pathological response was
      demonstrated in 12/20 patients (60%), a microscopic residual tumor in 7 patients
      (35%), and residual disease <1cm in 1 patient (5%). CONCLUSION: This study showed
      a particularly high rate of pathologic responses (T(0)+T(mic): 95%) and of local
      control. We don't know yet if surgery is a real necessity or if it could be less
      extended after concomitant chemoradiation.

PMID- 16446609
TI  - [Short interpregnancy intervals: risk factors and perinatal outcomes].
AB  - OBJECTIVES: To study risk factors and perinatal outcomes in short interpregnancy
      intervals. MATERIALS AND METHODS: Retrospective study, between 1995 and 2001,
      comparing women with short interpregnancy intervals (<6 months, n = 192) and
      women controls (interpregnancy intervals between 18 and 23 months, n = 210). The
      analysis included demographical and social factors, maternal medical histories
      and perinatal outcomes for the 2(nd) pregnancy. RESULTS: Risk factors of short
      interpregnancy intervals were: young age, no anterior contraception, celibacy,
      medical history of intrauterine fetal death or medical pregnancy termination and
      high parity and gestity. The patients at risks of short interpregnancy intervals
      often belong to little supported social background, are generally without
      profession and often leave against medical opinion. The short interval between
      pregnancies is associated to a high score of prematurity (19% vs 8%, OR = 2.8, p
      < 0.001). CONCLUSION: These data suggest that obstetricians and other care
      providers need to be alert to these identifiable risk factors and then direct
      preventive strategies during and after pregnancy.

PMID- 16446610
TI  - [Trial of labor after previous cesarean delivery: review of the literature].
AB  - OBJECTIVE: The aim of this review was to relate the evolution of obstetrical
      management of delivery in women who had previously undergone cesarean delivery
      and to search the studies supporting the choice of the mode of delivery. MATERIAL
      AND METHOD: We identified relevant studies through a computer search in the
      Medline database. RESULTS: After a period from 1980 to 2000 when the vaginal
      delivery had been increasingly recommended, a growth in the use of the planned
      cesarean delivery was observed. Recent studies report more evidence that uterine
      rupture is the result of trial of labor and that adverse perinatal outcomes are
      associated with uterine rupture. The risk of uterine rupture is increased with
      labor induction. The use of prostaglandins appears to be implicated in a
      significant increase of uterine rupture, and subsequently might be
      contraindicated in this situation. The use of oxytocin induced labor appears to
      increase the risk of uterine rupture. However, the level of adverse perinatal
      outcomes is low. The choice of the mode of delivery should take into account the
      likelihood of a further pregnancy, due to the increased risk of placental
      pathologic conditions depending on the number of repeated cesarean sections.
      CONCLUSION: An optimal decision for the mode of delivery should be shared with
      the pregnant women and all these factors should be taken into consideration.

PMID- 16446611
TI  - [Time-course of neonatal precocious mortality between 1994 and 2003 at the Dakar
      University Teaching Hospital].
AB  - OBJECTIVE: To evaluate early neonatal mortality at the University Teaching
      Hospital and assess changes in the rate and causes during the last ten years.
      MATERIAL AND METHOD: We performed a retrospective analysis of neonatal deaths
      recorded at the Neonatal and Premature Unit (NPU) in 2003. The results were
      compared with earlier evaluations. Comparison of proportions was used for
      statistical analysis to eliminate the random element in rate variations. The
      significance threshold was < or =5%. RESULTS: We registered 364 neonatal deaths:
      243 among 4853 newborns in our maternity ward and 121 among 213 newborns
      transferred from a referring maternity. Early neonatal mortality rate 45.5 per
      1,000 live births. Mortality particularly concerned newborns with a birth weight
      < or =2,500 grams (66%) and Apgar scores < or =6. Early neonatal mortality fell
      significantly since 1994, while overall mortality remained high among newborns
      transferred from referring maternities. The most frequent causes were premature
      birth (49%), acute fetal distress (23%) and neonatal infection (18%). CONCLUSION:
      Early neonatal mortality has decreased remains at a high level. It could be
      improved by limiting the number of premature births, neonatal suffering and
      neonatal infection. In a parallel direction we recommend organizing a perinatal
      network in Dakar.

PMID- 16446612
TI  - [Pregnancy and delivery among adolescents under 15: a study of 181 cases in
      French Guiana].
AB  - OBJECTIVE: The purpose of this study were to determine the effects and
      consequences of premature pregnancy and childbirth among adolescents under 15
      years of age in French Guyana. MATERIAL AND METHODS: A retrospective field-case
      study between the 1(st) and the 31(st) December 2001 identified 181 births among
      adolescents aged 14 years and under. Comparisons were made with 181 births among
      18-year-old first-time mothers taking place over the same period. RESULTS: 1.55%
      of all births in the maternity ward at St Laurent-du-Maroni Hospital involved
      adolescents under the age of 15. 24.6% of these young mothers were enrolled in
      secondary school, 21% were beneficiaries of the national social security health
      insurance and 61% of them were born outside Guyana. Pre-natal monitoring was less
      frequent among the group of teenage mothers, and preterm labor (0.04 < p < 0.05),
      anemia (0.02 < p < 0.03) and Chlamydiae trachomatis infections (0.03 < p < 0.04)
      are more frequent. There is no significant difference regarding high blood
      pressure, diabetes, or infectious diseases (except from Chlamydiae) or regarding
      labor and delivery. Mean birth weight was lower (p = 0.01) and the Apgar score
      was more often less than 7 at the first minute (p < 0.05) among newborn of
      teenage mothers. CONCLUSION: While pregnancies among younger teenagers appear to
      indicate a higher level of associated medical problems, a more thorough pre-natal
      check-up program would certainly reduce the number of problem related cases. The
      extremely high proportion of teenage pregnancies in the West of French Guiana has
      become a major public health issue for the entire region.

PMID- 16446613
TI  - [Short- and long-term consequences of prenatal exposure to cannabis].
AB  - OBJECTIVE: Cannabis is one of the most commonly used drugs by pregnant women. The
      objective of this review of literature was to examine the association between
      cannabis use during pregnancy and effects upon growth, cognitive development
      (memory, attention, executive functions...) and behavior of newborns, children
      and teenagers. MATERIAL AND METHODS: We searched for articles indexed in the
      medline database from 1970 to 2005. The following terms were used in the
      literature search: cannabis/marijuana, pregnancy, fetal development, newborn,
      prenatal exposure, neurobehavioral deficits, cognitive deficits, executive
      functions, cannabinoids, reproduction. Most of the articles were published in
      English. RESULTS: Cannabis use during pregnancy is related to diverse
      neurobehavioral and cognitive outcomes, including symptoms of inattention,
      impulsivity, deficits in learning and memory, and a deficiency in aspects of
      executive functions. It seems difficult to identify complications, such as lower
      birth weight, only attributable to cannabis as opposed to the multiple perinatal
      complications associated with tobacco smoking. CONCLUSION: In addition to alcohol
      and cigarettes, information should be given to women about the potentially
      harmful effects on fetal development, newborns, children and teenagers of smoking
      cannabis. Therefore, it seems necessary to develop prevention programs on this
      subject.

PMID- 16446615
TI  - [Dermoid cyst of the urachus: a case report and review of the literature].
AB  - The urachus, a normal embryonic remnant of the primitive bladder dome, exists as
      a fibrous cord in adult. Urachal disorders are not exceptional, and are
      expression of incomplete regression. Diagnosis is generally ultrasonographic,
      rarely clinical. We report a case of urachal dermoid cyst revealed by abdominal
      pain and underline the diagnostic difficulties related to this unusual
      localization.

PMID- 16446614
TI  - [Post-menopausal endometrial tuberculosis].
AB  - A 69-year-old menopaused woman, presented a 2-month history of metrorrhagia. We
      suspected a malignant disease, but, the histopathologic examination of biopsies,
      found an endometrial inflammation without malignant cells. Culture for
      mycobacteria showed a Mycobacterium tuberculosis. A course of four-drug
      antituberculous therapy was started and the patient recovered. Tuberculosis
      remains a common disease, but genital infection is infrequent. Usually, it
      concerns young infertile women from non-industrial countries. More attention
      should be paid to this disease. Women, irrespective of their age, should be
      investigated for silent or subclinical genital symptoms, with mycobacterial
      examination.

PMID- 16446616
TI  - [Postpartum mania induced by Bromocriptine: a case report].
AB  - The postpartum period is a high-risk period for occurrence of mood disorders
      (depression, mania) particularly for women with a history of bipolar disorder. We
      report the case of a woman with a postpartum mania episode with psychotic
      features induced by bromocriptine. This case report highlights the need to
      systematically explore the personal history of pregnant women in search of mood
      disorder which may proscribe use of bromocriptine.

PMID- 16446617
TI  - [Angular pregnancy at eleven weeks gestation on a fibromyomatous uterus].
AB  - Reported cases of angular pregnancy, which by definition corresponds to pregnancy
      developing in a uterine horn, are rare. Etiologies as well as the diagnostic and
      therapeutic strategies are discussed. The anatomic modifications resulting from
      uterine fibromyoma and affecting embryo nidation in the uterine cavity of the
      uterus are the leading cause of angular pregnancy. The course of pregnancy
      depends on the evolution of the fibromyoma. Treatment therefore depends on the
      clinical course. Early diagnosis is essential for conservative treatment. In the
      case presented here, angular pregnancy was diagnosis following development of
      aseptic necrobiosis, the most common complication of fibromyosma.

PMID- 16446620
TI  - [Update on the neurological consequences of HIV-1 infection (2006)].

PMID- 16446621
TI  - [HIV and the central nervous system].
AB  - Central nervous system complications are common in HIV-1 infected patients and
      occur either as a result of concomitant immunosuppression (opportunistic
      infections, lymphoma and tumors), as a primary manifestation of HIV infection, or
      as an adverse effect of therapy (immune restoration and toxicity). These
      complications contribute largely to patient morbidity and mortality. In the era
      of highly active antiretroviral therapy (HAART) these disease states have changed
      in presentation, outcome and incidence. We review in detail the epidemiology,
      pathogenesis, clinical features, diagnosis, and management of these disorders.

PMID- 16446623
TI  - [Physiopathogenic aspects of HIV-associated primary brain lymphomas].
AB  - HIV-associated Primary brain lymphomas (PBLs) are usually diffuse, large B-cell
      lymphomas (DLBCLs). In contrast to those occurring in immunocompetent patients,
      nearly all HIV-associated PBLs are associated with Epstein-Barr virus (EBV).
      Since viral latency proteins are target antigens for anti-viral cytotoxic T
      lymphocytes, the double immunodeficiency (HIV infection, central nervous system
      microenvironment) favors the expression of viral latency proteins (LMP-1, EBNA2).
      These proteins play a major role in immortalization and transformation of
      infected B lymphocytes through cell cycle activation and apoptosis inhibition.

PMID- 16446622
TI  - [New trends in progressive multifocal leukoencephalopathy].
AB  - Infection by Polyomavirus JC is a model of chronic active viral infection,
      closely controlled by the immune system. Progressive multifocal
      leucoencephalopathy (PML) is a deadly demyelinating disease of the central
      nervous system, consecutive to the lytic infection of oligodendrocytes by JC
      virus. Reactivation of JC virus occurs only in the setting of severe cellular
      immune deficiency. During the last 25 years, the incidence of PML has
      significantly increased related to the AIDS pandemic and, more recently, to the
      growing use of immunosuppressive drugs. There is no specific antiviral treatment
      for PML. Nevertheless, the availability of highly active antiretroviral therapy
      has changed the clinical course of PML in HIV-infected individuals. One-year
      mortality has decreased from 90 percent to approximately 50 percent as a result
      of reconstitution of the immune system. Recent advances in JC virus biology give
      new perspectives to the pathogenesis of PML. New trends in the understanding of
      the cellular immune response against the JC virus have direct implications for
      patient management and may lead to develop future strategy of immunotherapies for
      PML.

PMID- 16446624
TI  - [Mitochondrial cytopathies associated with HIV infection].
AB  - The tremendous progress achieved during the last few years with the use of highly
      active antiretroviral therapy in suppressing HIV replication together with
      improvements in immunity have been tempered by a growing number of new adverse
      effects. Mitochondrial toxicity is one aspect of these long-term toxicities of
      antiretroviral drugs, with the role of nucleoside analogs particularly
      underlined. Some cases of impaired mitochondrial function have been clearly
      identified, such as pancreatitis due to didanosine, neuropathy due to
      zalcitabine, myopathy due to zidovudine, and lactic acidosis due to stavudine.
      These mitochondrial toxicities can affect several organs, presenting different
      patterns of symptoms: from asymptomatic to states with few symptoms despite huge
      metabolic abnormalities whose prognosis is immediately life-threatening. Beyond
      the inhibition of DNA polymerase gamma using nucleoside analogs, responsible for
      decreasing mitochondrial DNA in certain targeted organs, it appears that several
      physiopathologic mechanisms interact to explain this observed toxicity, HIV
      itself plays a role, and the underlying genetic pool needs to be better
      identified. Such cases mean that, it is imperative to avoid cumulated toxicities
      caused by associated treatments. With serious cases, or persistent symptoms
      despite discontinuing the nucleoside analogs responsible for such toxicity, one
      must propose vitamins, mitochondrial co-factors, or anti-oxidants. However, the
      future lies in the use of potent, less toxic nucleoside analogs, and in
      developing compounds belonging to other classes of antiretrovirals.

PMID- 16446625
TI  - [Muscular complications of human immunodeficiency virus (HIV) infection in the
      era of effective anti-retroviral therapy].
AB  - Introduction of highly active antiretroviral therapy (HAART) has dramatically
      modified the natural history of HIV disease, but lengthening the survival of HIV
      infected individuals has been associated with an increasing prevalence of
      iatrogenic conditions. Muscular complications of HIV infection are classified as
      follows: (1) HIV-associated myopathies and related conditions including
      polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative
      lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitis, myasthenic
      syndromes, and chronic fatigue; (2) iatrogenic conditions including mitochondrial
      myopathies, HIV-associated lipodystrophy syndrome, and immune restoration
      syndrome; (3) opportunistic infections and tumor infiltrations of skeletal
      muscle; and (4) rhabdomyolysis. These features are described in the present
      review.

PMID- 16446626
TI  - [Role of immunity in the development of progressive multifocal
      leukoencephalopathy: a report of three patients with type B lymphoma and humoral
      immunodeficiency and six others with acquired immunodeficiency syndrome].
AB  - INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) caused by JC virus
      (JCV) mostly occurs in different conditions of impaired cellular immunity like
      acquired immunodeficiency syndrome (AIDS) and rarely when humoral immunity is
      involved. PML remains unusual although there is a high prevalence of JCV among
      the population and immunosuppression is not rare because of chemotherapies.
      METHODS: We present two groups of patients: first, we studied reports of three
      patients suffering from lymphoma type B who developed a PML, proved by cerebral
      biopsy. The second group included six HIV-infected patients who developed a PML.
      No biopsy was made but MRI and the physical examination suggested strong
      arguments for the diagnosis. RESULTS: In the first group, PML was furthered by
      humoral immunosuppression (rate of immunoglobulin G under 4 g/l). Average
      survival was five months. In the second group, HIV-infected patients had a
      survival range from 2 to 58 months after the first PML symptoms and one of them
      is still alive. CONCLUSION: Humoral immunosuppression in lymphoma can contribute
      to the development of PML. PML prognosis is often severe but prolonged survivals
      were described. So it is necessary to restore a sufficient immunity level. But
      immunity failure may be insufficient to lead to PML. In the case of lymphomas,
      the role of malignant lymphocytes in multiplication and mutation of JCV might be
      an interesting pathophysiological hypothesis.

PMID- 16446627
TI  - [Resolution of choreic movements associated with HIV encephalitis with anti
      retroviral therapy].
AB  - INTRODUCTION: Infection of the central nervous system with human immunodeficiency
      virus (HIV) can be associated with movement disorders. CASE REPORT: A case of
      chorea during HIV encephalitis which responded well to antiretroviral therapy is
      reported. Choreic movements disappeared with a decrease of MRI lesions observed
      in basal ganglia. CONCLUSION: The efficacy of anti-retroviral therapy in choreic
      movements, a rare syndrome with HIV encephalitis, can be underlined.

PMID- 16446628
TI  - [Pure trigeminal motor neuropathy presenting with temporo-mandibular joint
      dysfunction in a patient with HIV and HCV infections].
AB  - Pure trigeminal motor neuropathy (PTMN) is a rarely described condition. We
      report the case of a 41-year-old woman infected with the human immunodeficiency
      virus (HIV1) and hepatitis C virus who presented with weakness of left temporalis
      and masseter muscles and painful left temporomandibular joint dysfunction (TMD) a
      few months after cerebral toxoplasmosis revealing acquired immunodeficiency
      syndrome (AIDS). Magnetic resonance imaging revealed severe wasting and fat
      replacement of the left temporalis, pterygoid and masseter muscles and showed
      neither abnormalities in the left motor nucleus of the trigeminal nerve nor
      compression of the left trigeminal nerve. Electromyographic examination gave
      evidence of denervation in the left temporalis, masseter and pterygoid muscles
      and blink reflex studies were normal, confirming the diagnosis of PTMN which was
      probably secondary to HIV and HCV co-infection.

PMID- 16446630
TI  - [How to diagnose psychogenic tremors].

PMID- 16446629
TI  - [HIV infection presenting with bilateral optic neuropathy].
AB  - We report the case of a 57-year-old man who presented bilateral subacute and
      painless optic neuropathy after meningopolyradiculitis revealing a primary human
      immunodeficiency virus infection. Both antiretroviral and steroid treatments were
      ineffective. Clinical symptoms and evolutive pattern were consistent with a
      mechanism of microvascular ischaemia of the optic nerve head. Optic neuropathies
      related to HIV infection are rare compared to those resulting from opportunistic
      infections. There are several pathophysiological mechanisms involved.

PMID- 16446631
TI  - [Treatment of dementia with Lewy bodies].
AB  - Dementia with Lewy bodies (DLB) is known for its partial resistance and
      hypersensitivity to some treatments, but DLB is treatable with cholinesterase
      inhibitors, sometimes better than in Alzheimer's disease. Cholinesterase
      inhibitors have a symptomatic effect on cognition and behavior. Nevertheless, new
      antipsychotics are sometimes also useful to manage psychotic symptoms. Although
      DLB patients respond less well to levodopa than patients with Parkinson's
      disease, 75 percent of DLB patients improve with levodopa, which is the best
      tolerated dopaminergic agent. Nonpharmacological strategies include speech
      therapy, physiotherapy, psychotherapy, and educational support groups for care
      givers.

PMID- 16446632
TI  - [Borderlines types of multiple sclerosis].
AB  - Multiple sclerosis (MS) has been described for more than a century, but its cause
      remains unknown. Numerous reports have been written concerning borderline types
      of the disease. In the present paper we present the pseudo-tumoral variants of MS
      (so called Balo's, Marburg's and Schilder's forms), demographic variants (young
      and elderly onset of MS), related disorders (neuromyelitis optica and acute
      demyelinating encephalomyelitis). We also discuss the differential diagnosis with
      other auto-immune diseases.

PMID- 16446633
TI  - [Follow-up of excision of cutaneous melanoma: sentinel node biopsy, lymph node
      ultrasound or clinical surveillance alone?].

PMID- 16446634
TI  - [How many dermatologists are required in France?].

PMID- 16446635
TI  - [Antiseptics: not an automatic choice].

PMID- 16446636
TI  - [Assessment of a general practitioner training campaign for early detection of
      cutaneous melanoma in the Haut-Rhin department of France].
AB  - INTRODUCTION: Dermatologists frequently provide training for general
      practitioners, but such training is not systematic and evaluation is rare.
      MATERIALS AND METHODS: A training campaign for general practitioners and
      occupational physicians in melanoma screening was carried out in the Haut-Rhin
      Department of France in 2004. The 630 general practitioners and 120 occupational
      physicians in this geographic department received repeated mail together with
      materials (posters and booklets) for their waiting rooms, and they were invited
      to attend medical training sessions. The sessions consisted of 10 photographs for
      initial evaluation, provision of epidemiological information, training in
      identification of subjects at risk and diagnosis of pigmented lesions, with a
      further 10 photographs for evaluation at the end. The 20 evaluation photographs
      were randomly selected for each session from 40 photographs comprising 18 cases
      of melanomas, 14 of nevi, 4 of basal cell carcinomas and 4 of seborrheic
      keratoses. At the end of each session, the physicians returned 2 anonymous
      questionnaires containing their overall assessment of the campaign (Q1) and their
      answers concerning the 20 evaluation photographs (proposed diagnosis and
      management strategy) (Q2). The questionnaires were then analyzed. The 40
      evaluation photographs were also tested on 47 dermatologists. RESULTS: Three
      hundred and fifty physicians - 278/630 general practitioners (44%) and 72/120
      occupational physicians (60%) - attended 18 medical training sessions. Response
      levels for questionnaires Q1 and Q2 were 88% and 90% respectively. Almost all of
      the physicians involved considered the campaign to be warranted. At the end of
      the training sessions, 96% felt they were better equipped to identify subjects at
      risk for melanoma and 53% (58% of general practitioners and 39% of occupational
      physicians, p=0.03) felt they had greatly improved their ability to diagnose
      pigmented lesions. The median number of correct replies concerning the evaluation
      photographs increased from 6/10 to 7/10 between the initial evaluation
      photographs and the final evaluation photographs (p<0.0001), with no difference
      being seen between the general practitioners and occupational physicians. The
      median number of correct replies from the 47 dermatologists was 35/40 (8.75/10).
      The most striking improvement noted during the campaign concerned the ability to
      identify melanomas. The figure rose from an initial 59% at the start of the
      session (initial evaluation photographs) (versus 86% for the dermatologists) to
      84% by the end of the session (final evaluation photographs) (p<0.0001). The
      management strategy proposed for photographs of melanoma (irrespective of the
      proposed diagnosis) was judged "appropriate" in 86% of cases at the start of the
      session versus 94% at the end of the session (p<0.001). Seborrheic keratosis was
      correctly identified in 43% of cases by the general practitioners/occupational
      physicians versus 75% by the dermatologists, and was confused with melanoma in
      22% of cases by the general practitioners/occupational physicians versus 5% by
      the dermatologists. No improvement was seen during the training session in terms
      of the ability of the general practitioners/occupational physicians to correctly
      identify seborrheic keratosis. The majority of participants indicated their
      willingness to participate in the screening program and asked to receive
      information on melanoma on a regular basis. DISCUSSION: This initial study shows
      the immediate impact of medical training sessions on general
      practitioners/occupational physicians to be important in terms of sensitization
      and moderate but significant in terms of improved diagnosis of pigmented lesions.
      The longer term impact, as well as the impact of the campaign on physicians not
      taking part in the medical training sessions, remains unknown. This study
      militates in favor of the involvement of general practitioners and occupational
      physicians in mass screening for melanoma in collaboration with dermatologists.
      The 2004 campaign in the Haut-Rhin Department also included information for the
      general public. The primary evaluation criterion of the campaign will be change
      in incidence of thick melanomas recorded by the departmental cancer registry.

PMID- 16446637
TI  - [Contact allergy to antiseptics: 75 cases analyzed by the dermato
      allergovigilance network (Revidal)].
AB  - AIM: To determine the clinical features of contact dermatitis caused by
      antiseptics and to ascertain whether the substance responsible is the antiseptic
      itself or the excipients. PATIENTS AND METHODS: A multicenter, retrospective
      study based on analysis of all cases reported over a 2-year period to the Dermato
      Allergology Vigilance network known as Revidal. Each dossier contained details of
      the clinical characteristics of lesions, the incriminated antiseptic, the mode of
      exposure and the results of patch tests done with the antiseptic in question.
      RESULTS: 75 patients (mean age: 44 years) were sensitized to chlorhexidine (14
      cases), hexamidine (20 cases), povidone iodine (14 cases), mercuric antiseptics
      (3 cases), triclocarban (Septivon, 17 cases), hexamidine-chlorhexidine
      chlorocresol (Cyteal, 4 cases), or chlorhexidine surfactant (Hibiscrub),
      cetrimide or chlorhexidine digluconate (Diaseptyl) (1 case each). Exposure was
      therapy-related (68 cases), work-related (6 cases; 5 in health workers and 1 in a
      cattle farmer due to povidone-iodine) or related to cosmetics (1 case,
      hexamidine). The clinical features consisted mainly of localized contact
      dermatitis, although generalized eczema occurred in 9 cases due to hexamidine
      contact. Sensitization was due to the antiseptic itself (53 cases) or to the
      excipients alone (22 cases), particularly in the 17 cases caused by Septivon. In
      27/75 cases (35%), patients exhibited polysensitization to antiseptics belonging
      to different chemical classes or to other topical drugs. CONCLUSION:
      Sensitization to antiseptics is probably not rare, with various sources of
      exposure being present in everyday life. Patch tests are essential for diagnosis
      in order to distinguish between antiseptic-related and excipient-related
      sensitization and to screen for polysensitization to topical drugs.

PMID- 16446638
TI  - [Eruptive pseudoangiomatosis in infant and newborns].
AB  - INTRODUCTION: Eruptive pseudoangiomatosis was first described in children in the
      form of an acute non-pruritic macular or papular rash that fades on application
      of a glass test and resolves within several days. Viral aetiology is suspected
      but has never been demonstrated to date. OBSERVATIONS: We discuss seven cases of
      infants presenting this disease: 5 boys and 2 girls aged 8 days to 16 months. The
      rash presented typical clinical features in all cases and affected the face and
      limbs in 6 of the 7 subjects. In one child, involvement of the face and back was
      observed with sparing of the limbs. The rash occurred after an episode of
      rhinolaryngeal infection in 3 cases and after gastrointestinal infection in 1
      case. Spontaneous resolution was seen within 3 to 10 days in 6 patients although
      a longer course lasting over 9 months was observed in one infant. In another
      patient, the rash appeared after surgery for mesoblastic nephroma. In one child,
      a similar rash was seen in both parents. Screening for infectious agents was
      negative for the two children from whom samples were obtained. DISCUSSION: This
      series of paediatric cases of eruptive pseudoangiomatosis is characterised by the
      very young age of one of the children, coexistence of the condition with a renal
      tumour in another child, the familial nature of the rash in a third child and
      unusually long disease duration in the final child. However, this series did not
      allow identification of the causative infectious agent or agents. Probably, as
      with other syndromes such as Giannotti-Crosti syndrome or "gloves and socks"
      syndrome, eruptive pseudoangiomatosis forms a clinical picture common to a non
      specific viral infection.

PMID- 16446639
TI  - [Cutaneous drug-reactions to nevirapine: study of risk factors in 101 HIV
      infected patients].
AB  - BACKGROUND: Several studies have shown a high prevalence of rash induced by
      nevirapine. However, there is little knowledge about the risk factors associated
      with nevirapine-induced rash. The aim of this study was to identify risk factors
      associated with the occurrence of rash during the treatment with nevirapine of
      HIV-infected patients. METHODS: A retrospective study was conducted in the
      dermatology department of Besancon university teaching hospital between November
      1998 and September 2001. The study included all HIV-infected patients receiving
      HAART regimens that included nevirapine. The following data were collected: age,
      sex, CDC classification of HIV, CD4 and CD8 lymphocyte counts, plasma HIV RNA
      load, hepatitis B, C and cytomegalovirus serostatus, history of drug allergy,
      concomitant medication (other antiretroviral drugs, corticosteroids,
      antihistamines). Univariate analysis was performed using a Chi2 test or Fischer's
      test and Student's t test. Fischer's test and the Cox proportional hazards model
      were used in the multivariate analysis. RESULTS: During the study period, 101 HIV
      infected patients (74 men and 27 women; mean age: 41.6 +/- 10.3 years) were
      treated with HAART regimens including nevirapine. Fourteen developed cutaneous
      drug-reactions attributable to nevirapine (13.86%). We observed 13 cases of
      maculopapular exanthema and 1 case of DRESS. In the univariate analysis, female
      gender (p=0.002), plasma HIV RNA load > 10,000 copies/ml (p=0.05), heterosexual
      transmission (p=0.002) and abacavir treatment (p=0.05) constituted risk factors
      associated with rash. In the multivariate analysis, only female gender (p<0.0001)
      and plasma HIV RNA load > 10,000 copies/ml (p=0.0007) were associated with rash.
      DISCUSSION: The results of this study confirm the high frequency of toxidermy
      associated with nevirapine therapy. The risk factors associated with occurrence
      of rash due to nevirapine therapy were female gender and plasma RNA > 10,000
      copies/ml. Several studies showed absence of any protective effect of
      antihistamines and corticosteroids in preventing the cutaneous adverse reactions
      associated with nevirapine. The identification of risk factors closely associated
      with nevirapine-induced rash could help physicians determine new strategies for
      safer use of nevirapine in the HAART regimen.

PMID- 16446640
TI  - [Epidemiology of cutaneous melanoma: descriptive data in France and Europe].
AB  - INTRODUCTION: The incidence of melanoma and the resulting mortality have been the
      subject of many studies. However, controversy remains as to the interpretation of
      the number of cases observed and the existence of an actual "epidemic" of
      melanomas in fair-skinned populations. OBJECTIVES: Analyze the descriptive
      epidemiological data available concerning cutaneous melanomas in France and in
      Europe. METHODS: Data regarding incidence and mortality published in the
      literature and on the Internet were reviewed and analyzed. RESULTS: In France,
      between 1980 and 2000, the standardized worldwide population incidence rate of
      melanoma increased from 2.4 to 7.6 per 100.000 inhabitants/years in men and from
      3.9 to 9.5 in women. In the Haut-Rhin department in France, where Breslow indexes
      are registered, the increase in incidence was accompanied by an increase in the
      proportion of thin melanomas. In the year 2000, the estimated number of new cases
      of cutaneous melanomas was of 7231, with 58 p. 100 female and 42 p. 100 male
      cases. Great geographical disparity among the 9 departments in France equipped
      with registers was noted. This increase in incidence was accompanied by an
      increase in mortality. Between 1969 and 1997, mortality due to melanoma was
      multiplied by 2.7 in women and by 2.9 in men. In the year 2000, 1364 deaths were
      attributed to a melanoma. The standardized worldwide mortality rates were of
      1.6/100000 inhabitants/years in men and 1.1/100000 inhabitants/years in women. In
      Europe, a great increase in the incidence and mortality has been registered in
      all countries since the nineteen fifties. It was earlier and greater in northern
      European countries, followed by western European countries, and finally by
      eastern and southern countries. There was great geographical disparity, with a
      double decreasing North-South East-West gradient. Analysis of the recent trends
      in development, in countries with high incidence such as those of northern
      Europe, showed a trend towards the stabilization in the incidence and decreased
      mortality in young adults. DISCUSSION: In France, as in Europe, the extensive
      increase in incidence of melanoma and resulting mortality is a reality, reaching
      a peak in the northern European countries. The decrease in mortality observed
      recently in young cohorts in these countries and in Eastern Europe may announce
      an ultimate decrease in the older populations and the rest of Europe. Massive
      primary and secondary prevention campaigns seem effective and warrant
      reinforcement.

PMID- 16446641
TI  - [Gnathostomiasis: an emerging parasitic disease?].
AB  - INTRODUCTION: Human gnathostomiasis is a parasitic disease caused by the
      ingestion of foods contaminated with the larvae of various species of
      Gnathostoma. This zoonosis is currently endemic in Asia and Central America. CASE
      REPORT: A 46-year-old French woman resident in Vietnam presented with
      intermittent pruritic swelling of the hand, present for one year, coupled with
      eosinophilia. The patient's history and serological testing confirmed the
      suspected diagnosis of gnathostomiasis. A favorable outcome was attained on
      treatment with albendazole. DISCUSSION: This case, together with several others
      recently reported in France and Europe, underlines the need to inform travelers
      and migrants to endemic regions of the risks associated with eating raw or
      marinated fish.

PMID- 16446642
TI  - [Primary cutaneous extraskeletal Ewing's sarcoma].
AB  - BACKGROUND: Cutaneous extraskeletal Ewing's sarcoma is rare, being seen
      principally in children. We report a case of cutaneous sarcoma in the sole of the
      foot in a child. CASE REPORT: A 9-year-old child with no medical history of note
      was presenting a skin tumor for 3 months on the heel of the right foot. This
      tumor was burgeoning and painful and measured 3.5 cm in diameter; it was
      ulcerative at the surface and covered with a crust. Histological and
      immunohistochemical examinations confirmed the diagnosis of Ewing's sarcoma.
      Staging examinations proved negative and the patient underwent polychemotherapy,
      resulting in complete regression of the tumor. COMMENTS: Until 1998, 37 cases of
      cutaneous and subcutaneous Ewing's sarcoma were reported, being seen in 21 girls
      and 16 boys. Mean age at diagnosis was 15 years and mean tumor size was 3 cm
      (range: 1 to 12 cm). The tumors were observed throughout the body, being seen in
      the sole of the foot in 2 cases. Confirmation of the diagnosis was made by
      histological examination (malignant proliferation of small round cells in the
      dermis), immunohistochemical examination (CD99+) and cytogenetic analysis
      (translocation between chromosomes 22 and 11). The prognosis for cutaneous
      Ewing's sarcoma appears more favorable than that of Ewing's sarcoma in bone. Of
      the 37 patients treated, 7 had metastases and 2 presented relapse. Treatment for
      cutaneous Ewing's sarcoma, though not codified, consists of polychemotherapy
      associated with surgery and/or radiotherapy.

PMID- 16446643
TI  - [Multiple abscesses induced by self injection of zolpidem].
AB  - BACKGROUND: Zolpidem, a hypnotic drug, is occasionally taken in high doses by
      some drug addicts for its hallucinogenic properties. CASE REPORT: We report the
      original observation of a young female addict who developed aseptic cutaneous
      abscesses on the forearms and feet induced by self injection of powdered
      zolpidem. Histopathological analysis revealed birefringent vegetal structures.
      DISCUSSION: The shape and size of the birefringent structures are those of
      microcrystalline cellulose, an excipient used in zolpidem pills. The same
      structures have been identified by microscopic examination of a zolpidem tablet
      dissolved in water.

PMID- 16446644
TI  - [Chromium-induced vasculitis-like purpuric allergic contact dermatitis].
AB  - INTRODUCTION: Purpuric allergic contact dermatitis is a rare and poorly
      understood condition. CASE REPORT: A 27-year-old male patient with a personal
      history of atopic dermatitis since childhood consulted for chronic papular
      purpuric rash present for 7 years. Moderate pruritus was seen. Profuse lesions
      were observed on the palms and soles and on the upper and lower limbs, with
      sparing of the trunk. These lesions consisted of purpuric papules, in some cases
      with crusts, forming large plaques. The clinical picture was initially suggestive
      of vasculitis, but this diagnosis was ruled out by histological examination and
      laboratory tests. Skin patch tests were evocative of chromium-induced contact
      dermatitis. Retrospective directed history-taking confirmed the relevance of the
      latter test since it revealed regular wearing of leather clothing. Lasting cure
      was achieved following eradication of the allergen. DISCUSSION: Reports of
      contact purpuric dermatitis are rare. This condition has been described
      principally for allergens consisting of rubber or dyes used in clothing. Our case
      was notable on account of the severity of the lesions, mimicking vasculitis, as
      well as the novelty of the incriminated allergen, chromium, found in leather
      garments. It underlines the value of routine skin patch tests in the event of
      chronic non-specific dermatitis. To our knowledge, this is the first reported
      case of chromium-induced purpuric allergic contact dermatitis.

PMID- 16446645
TI  - [Fluvastatin-induced dermatomyositis].
AB  - BACKGROUND: Dermatomyositis is a rare inflammatory dermatosis for which an
      iatrogenic origin has been described in very few cases. We report a case of
      dermatomyositis occurring after fluvastatin intake. CASE REPORT: A 76-year-old
      male patient sought medical attention for a photodistributed rash and
      considerable muscular weakness present for one month. Two months earlier,
      fluvastatin had been introduced following the discovery of dyslipidemia. Serum
      creatine phosphokinase levels were elevated. Histological examination of a muscle
      biopsy was consistent with a diagnosis of dermatomyositis. Investigation for
      neoplasia and associated autoimmune disease proved negative. All clinical and
      laboratory abnormalities diminished spontaneously without recourse to
      corticosteroids within one month of the final intake of fluvastatin. After a
      follow-up period of three years, no recurrence was observed and no signs of
      neoplasia or connectivitis were found. DISCUSSION: Iatrogenic dermatomyositis has
      only been reported in rare cases. Certain drugs have been incriminated, notably D
      penicillamine. Six cases of drug-induced dermatomyositis have been described with
      statins: simvastatin, atorvastatin, pravastatin and lovastatin. Of these cases,
      only one resolved spontaneously after withdrawal of the drug alone without use of
      corticosteroids. Our case concerns intake of fluvastatin, an HMG-CoA reductase
      inhibitor with rare though well-known muscular side effects: elevated serum CPK,
      myalgia and rhabdomyolysis. Six cases of polymyositis have also been reported.
      Ours is the first case of dermatomyositis described with this category of
      statins. It is also the second reported case showing improvement after withdrawal
      of the lipid-lowering agent and without corticosteroids. Thus in cases of
      dermatomyositis, this iatrogenic picture should be sought routinely.

PMID- 16446646
TI  - [Hypersensitivity to fluindione (Previscan). Positive skin patch tests].
AB  - INTRODUCTION: Fluindione (Previscan) is an oral anticoagulant belonging to the
      vitamin K antagonist class and is very widely used in France. While bleeding is a
      common complication, severe immunoallergic reactions are less frequent. The
      authors report a case of drug-induced hypersensitivity syndrome. CASE REPORT: A
      75 year-old woman was hospitalized for diffuse erythematous papular rash
      associated with facial oedema. These symptoms appeared 3 weeks after the
      beginning of treatment with fluindione, allopurinol and perindopril. Laboratory
      tests showed hyperleukocytosis, mixed hepatitis and moderate renal failure, with
      the entire picture being evocative of drug-induced hypersensitivity reaction. The
      eruption was associated with eosinophilia, hepatic cytolysis with cholestasis,
      and acute renale failure. While allopurinol and perindopril were stopped
      definitively, fluindione was only suspended temporarily following overdosage. On
      reintroduction, rapid recurrence of clinical and biologic signs was observed with
      increased severity. The skin rash resolved completely on withdrawal of the drug.
      Patch tests performed later were positive for fluindione and negative for
      allopurinol and perindopril. DISCUSSION: These manifestations were consistent
      with the diagnosis of drug-induced hypersensitivity syndrome due to fluindione.
      Very few cases have been described with fluindione despite widespread
      prescription of the treatment is in France. While there may be no skin
      involvement, immunoallergic signs such as fever, hepatitis and acute tubular
      interstitial nephritis have been described with fluindione and these may be
      related to this syndrome (DRESS - Drug Reaction with Eosinophilia and Systemic
      Symptoms). Skin patch testing, which is easily performed, can be extremely
      helpful in determining a causal relationship with medication.

PMID- 16446647
TI  - [Aseptic meningitis during Sweet syndrome].
AB  - BACKGROUND: Sweet syndrome is a neutrophilic skin disease that can involve
      extracutaneous signs. Here we describe a case of aseptic meningitis, a rare
      potential extracutaneous sign of Sweet syndrome. CASE REPORT: A 42-year-old man
      was hospitalized for non-pruritic maculoerythematous skin lesions of the legs and
      back with subsequent myalgia. A histology specimen taken from a skin lesion
      revealed an acute neutrophilic disease consistent with Sweet syndrome. Marked
      inflammation and cholestasis were observed. Systemic corticosteroid therapy was
      given and resulted in good clinical and laboratory response. Two weeks later, in
      a setting of gradual dosage reduction, the patient was hospitalized for intense
      headaches associated with meningeal irritation in an inflammatory context. Liver
      function tests were again abnormal. We concluded on a diagnosis of Sweet syndrome
      complicated by aseptic meningitis and hepatic sites. Investigation for underlying
      disease, particularly digestive or hematologic, was negative. A favorable outcome
      was achieved following administration of higher doses of systemic
      corticosteroids. DISCUSSION: Aseptic meningitis constitutes an extracutaneous
      localization of Sweet syndrome. A multidisciplinary approach and exclusion of
      infectious origin are required in order to institute systemic corticosteroid
      therapy.

PMID- 16446648
TI  - [Specific pathways of pruritus?].

PMID- 16446650
TI  - [Leg ulcers: clinical and epidemiological study of hospital patients in Tunis].

PMID- 16446649
TI  - [Epidemiologic study of pemphigus in Marrakech: 134 cases].

PMID- 16446651
TI  - [Dermatologic complications in colostomy patients].

PMID- 16446652
TI  - [Chronic molluscum contagiosum infection prior to lymphoma].

PMID- 16446653
TI  - [Asymptomatic digital outgrowth of the index finger].

PMID- 16446654
TI  - [Oral manifestations of chronic graft-versus-host disease].

PMID- 16446655
TI  - [Common nevi].

PMID- 16446656
TI  - [Colostomy care].

PMID- 16446657
TI  - [Intralabial rotation flaps].

PMID- 16446658
TI  - [Klippel-Trenaunay syndrome: identification of a susceptibility gene coding for
      an angiogenic factor].

PMID- 16446659
TI  - [Angiosarcoma of the scalp: an unusual clinical presentation].

PMID- 16446660
TI  - [Side effects of anti-TNF alpha].

PMID- 16446673
TI  - The changes in running performance and maximal oxygen uptake after long-term
      training in elite athletes.
AB  - AIM: The relationship between VO2max (mL x kg(-1) x min(-1)) and running
      performance has been assessed in cross-sectional studies. Follow-up studies of
      the long-term effects of running training on the changes in performance and
      VO2max have not been undertaken. METHODS: Twenty-five male endurance-trained
      (MET) and 8 female endurance-trained (FET) athletes were tracked over 4 years. In
      each event the athletes were divided into Class A, including half the number of
      athletes with the best performances, and Class B. VO2max, examined at the end of
      the competitive season, and the best performance was chosen each year. RESULTS:
      After 3 years of training, in MET and FET athletes the performance improved by
      1.77% and 0.69% (P<0.01 and P=0.579), respectively. In Class A runners, training
      resulted in non-significant increase in performance (-0.04%) (P=0.982) and in
      Class B runners, performance increased by 3.16% (P=0.001). In all groups VO(2max)
      remained essentially unchanged. Longitudinal changes in the VO2max were not
      related with the changes in running performance in any group. CONCLUSIONS: This
      study show than in older runners with more years of training, heavy training does
      not produce improvements in running performance neither changes in the VO2max. It
      is possible that these elite athletes have reached the plateau in their
      performance; although unlikely, some improvement in training techniques may
      happen and break the present limit. In younger runners with less years of
      training, heavy training produce improvements in running performance without
      changes in the VO2max. These athletes that had not attained his biological limits
      at the beginning of study improved the performance in competition and it is quite
      probable that this improvement be due to training. The changes in performance
      were not related to changes in VO2max. Consequently, another physiological or
      psychological variables must be studied by longitudinal form to explain the
      variability of performance in competition.

PMID- 16446674
TI  - Relationships and significance of lactate minimum, critical velocity, heart rate
      deflection and 3 000 m track-tests for running.
AB  - AIM: The running velocities associated to lactate minimum (V(lm)), heart rate
      deflection (V(HRd)), critical velocity (CV), 3.000 m (V(3000)) and 10 000 m
      performance (V10km) were compared. Additionally the ability of V(lm) and V(HRd)
      on identifying sustainable velocities was investigated. METHODS: Twenty runners
      (28.5+/-5.9 y) performed 1) 3,000 m running test for V3000; 2) an all-out 500 m
      sprint followed by 6x800 m incremental bouts with blood lactate ([lac])
      measurements for V(lm); 3) a continuous velocity-incremented test with heart rate
      measurements at each 200 m for V(HRd); 4) participants attempted to 30 min of
      endurance test both at V(lm)(ETV(lm)) and V(HRd)(ETV(HRd)). Additionally, the
      distance-time and velocity-1/time relationships produced CV by 2 (500 m and 3 000
      m) or 3 predictive trials (500 m, 3,000 m and distance reached before exhaustion
      during ETV(HRd)), and a 10 km race was recorded for V10km. RESULTS: The CV
      identified by different methods did not differ to each other. The results (m.min(
      1)) revealed that V(lm) (281+/-14.8)<CV (292.1+/-17.5)=V10km (291.7+/
      19.3)<V(HRd) (300.8+/-18.7)=V3000 (304+/-17.5) with high correlation among
      parameters (P<0.001). During ETVlm participants completed 30 min of running while
      on the ETV(HRd) they lasted only 12.5+/-8.2 min with increasing [lac].
      CONCLUSIONS: We evidenced that CV and Vlm track-protocols are valid for running
      evaluation and performance prediction and the parameters studied have different
      significance. The V(lm) reflects the moderate-high intensity domain (below CV),
      can be sustained without [lac] accumulation and may be used for long-term
      exercise while the V(HRd)overestimates a running intensity that can be sustained
      for long-time. Additionally, V3000 and V(HRd) reflect the severe intensity domain
      (above CV).

PMID- 16446675
TI  - Non-linear relationships between central cardiovascular variables and VO2 during
      incremental cycling exercise in endurance-trained individuals.
AB  - AIM: The purpose of this study was to examine the relationships between the
      central cardiovascular variables (cardiac output, stroke volume and heart rate)
      and oxygen uptake (VO2) during continuous, incremental cycle exercise to maximal
      aerobic capacity (VO2max). METHODS: Twenty-one moderately to highly trained males
      (n=19) and females (n=2) participated in the study. A baseline maximal exercise
      test was performed to measure VO2max. Following the initial VO2max test, cardiac
      output was measured (CO2 rebreathing technique) at rest and 3 times during each
      of 4 exercise trials (2 submaximal tests to 90% VO2max and 2 maximal tests).
      Stroke volume and arteriovenous O2 difference were calculated using standard
      equations. RESULTS: Significant non-linear relationships were found between all
      central cardiovascular variables and VO2 (P<0.01). A plateau in cardiac output at
      VO2max was identified in 3 subjects. Stroke volume plateaued at an average of
      37+/-12.5% of VO2max in 18 subjects and increased continuously to VO2max in 3
      subjects. The arteriovenous O2 difference progressively increased to VO2max in 17
      subjects and revealed a plateau response in 4 subjects. CONCLUSIONS: Our data
      suggest that there is a significant non-linear relationship between the central
      cardiovascular variables and VO2 during incremental exercise to VO2max.
      Furthermore, depending on the person, VO2max may be limited by cardiac output
      (evidence of cardiac output[Q] plateau) or peripheral factors (continued increase
      in Q).

PMID- 16446677
TI  - Characterization of arm-gun movement during air pistol aiming phase.
AB  - AIM: Air pistol shooting is a sport requiring extreme movement precision. The
      purpose of our study is to collect and analyze kinematic data of arm/gun complex
      during the pointing phase in order to characterize movement and between segment
      coordination by means of time and frequency domain analysis techniques. METHODS:
      Thirteen air pistol athletes participated to the recording sessions held at the
      10 m shooting range. Kinematic data of neck, shoulder, elbow, wrist and gun were
      collected during the aiming phase using an optoelectronic motion capture system.
      Displacement series were split up in slow drift and tremor components. Amplitude
      of the movement of each segment and strength of the relationship between adjacent
      segments were estimated in time domain respectively by means of standard
      deviation and coefficient of regression. Moreover, coherence and phase spectral
      functions were calculated to assess between-segment coupling at different
      frequencies. RESULTS: Significantly larger movements were seen for slow drift
      component with respect to tremor one for all segments especially for lateral
      movements. Higher between segment correlation were found for lateral direction
      and for slow drift component. The coherence calculated on vertical series of
      tremor component showed significant coupling at 1.5 Hz and 5-7 Hz with phase
      opposition between wrist and gun motion at 5-7 Hz. CONCLUSIONS: Slow drift motion
      appears to affect mainly lateral movements and all the segments were equally
      involved indicating a probable origin in postural body sway. Vertical
      displacements could be referred to shoulder and wrist motion with features
      typical of physiological tremor. Quantitative characterization of segments
      displacements during aiming phase may serve as a basis for scientific evaluation
      and training in competitive precision shooting.

PMID- 16446676
TI  - Blood lactate removal during recovery at various intensities below the individual
      anaerobic threshold in triathletes.
AB  - AIM: Optimal lactate removal was reported to occur at work-rate between 30% and
      70% VO2max. However, it has been recently recommended to quantify exercise
      intensity not in percentage of VO2max but in relation to validated metabolic
      reference points such as the individual anaerobic threshold (IAT) and the
      individual ventilatory threshold (IVT). The purpose of this study was to examine
      the effect on lactate removal of different recovery work-rates below the IAT
      defined calculating the difference (DT) between IAT and IVT, then choosing the
      IVT+50%DT, the IVT and the IVT-50%DT work-rates. METHODS: Eight male triathletes
      (VO2max 69.7+/-4.7, VO2IAT 52.9+/-4, VO2IVT 41.1+/-4.7 mL x kg(-1) x min(-1)),
      after a 6-min treadmill run at 75% of difference between IAT and VO2max,
      performed in a random order the following 30-min recovery treatments: 1) run at
      IVT(plus;50%DT), 2) at IVT, 3) at IVT(-50%DT), 4) passive. Blood lactate was
      measured at 1, 3, 6, 9, 12, 15, 20, 25, 30 minutes of recovery. RESULTS: All
      active recovery work-rates (from 50+/-5% to 67+/-4% VO2max) were within the range
      previously reported for optimal lactate removal, and significantly more efficient
      than passive recovery on lactate removal curve (% of accumulated lactate above
      rest value). However, significant differences (P<0.01) were found among active
      recovery intensities: the IVT(-50%DT) was the most efficient work-rate from the
      9th minute to 30th minute. CONCLUSIONS: In triathletes, the IVT(-50%DT) was the
      optimal work-rate for lactate removal; moreover none of the studied active work
      rate showed further lactate decrease after the 20th minute of recovery.

PMID- 16446678
TI  - Joint kinetics of the ankle and knee when running over obstacles.
AB  - AIM: When running over obstacles of increasing height, heelstrike (HS) runners
      switch to a forefoot (FF) landing pattern once a critical obstacle height is
      reached. The primary purpose of this study was to determine whether ankle or knee
      joint kinetic variables trigger the gait change from a HS to a FF striking
      pattern as obstacle height increases. METHODS: Ten subjects were filmed from the
      sagittal plane as they ran at their preferred running speed over a force platform
      during 6 obstacle height conditions ranging from 10% to 22.5% of standing height,
      as well as an additional baseline condition with no obstacle (0%). An inverse
      dynamics approach was utilized to calculate ankle and knee joint kinetics at each
      condition. RESULTS: Differences in joint kinetics did not occur until a height
      was reached at which the landing strategy changed from a HS to a FF landing
      pattern. Most differences occurred at the ankle joint, at which there was a
      greater maximum plantar flexor moment and a greater amount of energy absorbed
      when obstacles of sufficient height to require a FF landing pattern were
      negotiated. CONCLUSIONS: Although no variables were found which met all of the
      criteria necessary to be considered a determinant of the gait transition, there
      were variables which distinguished between a HS and FF strike landing pattern as
      obstacle height increased.

PMID- 16446679
TI  - Determinants of ball release speed in schoolboy fast-medium bowlers in cricket.
AB  - AIM: Studies investigating determinants of ball release speed have examined the
      technique and anthropometry of fast bowlers with little work being done on
      muscular strength. The aim of our study was to determine whether knee
      biomechanics during bowling and strength of the shoulder and knee could predict
      ball release speed. METHODS: Twelve cricketers, aged 16.6+/-0.7) years, from
      schools in Johannesburg, South Africa, volunteered for the study. Subjects were
      fast-medium bowlers (mean ball release speed of 29.2+/-1.8 m.s(-1)) and had been
      bowling for at least 5 years. Three accurate deliveries were filmed on an outdoor
      cricket pitch, in the sagittal plane with a high-speed digital camera recording
      at 250 frames per second. The mean ball release speed, knee angle at ball release
      and knee angle at front foot strike were determined using simple two-dimensional
      kinematics. On a separate day, peak concentric isokinetic muscle torque was
      measured for both knees and the dominant shoulder. RESULTS: Ball release speed
      was positively correlated to a straight knee at front foot strike (r=0.72,
      P=0.009) and at ball release (r=0.71, P=0.011). No significant correlation was
      found between ball release speed and any of the peak torque values (knee
      extension peak torque, r=-0.11, knee flexion peak torque, r=-0.08, shoulder
      internal rotation peak torque, r=0.21 and shoulder external rotation, r=0.29,
      P>0.05). A multiple regression model using knee angle at front foot strike and at
      ball release, and the angle at which peak torque is generated during shoulder
      internal and external rotation, predicted ball release speed (adjusted r2=0.85,
      P<0.002). CONCLUSIONS: We have confirmed that the angle of the front knee at the
      beginning and end of a delivery is an important correlate of ball release speed
      in schoolboy fast-medium bowlers. In addition we have also demonstrated that a
      multiple regression model based on knee kinematics and shoulder peak torque
      angles can be used to predict ball release speed.

PMID- 16446680
TI  - Anthropometry and somatotype of competitive female figure skaters 11-22 years.
      Variation by competitive level and discipline.
AB  - AIM: Variation in anthropometric characteristics and somatotype of female figure
      skaters by level of competition and discipline was examined. METHODS: 
      EXPERIMENTAL DESIGN: ANCOVA with age as the covariate was used to compare the
      anthropometry of skaters by level (test stream, pre-elite, elite) and discipline
      (free, dance, pair), while MANCOVA was used to compare somatotype. SETTING:
      purposive sampling reflecting the skating population by level and discipline was
      used to recruit skaters in 4 American, and 7 Canadian figure skating clubs.
      PARTICIPANTS: a total of 161 competitive female figure skaters 11-22 years of age
      (15.7+/-2.4 years) comprised the sample. MEASURES: a battery of 15 anthropometric
      dimensions was taken on each skater. Several dimensions, ratios and Heath-Carter
      somatotypes were derived. RESULTS: Test skaters are heavier and generally larger
      than pre-elite skaters. Test stream skaters also have larger limb circumferences,
      estimated calf and arm musculature, and a thicker sum of skinfolds, and are more
      endomorphic than pre-elite skaters. Elite skaters are more mesomorphic than pre
      elite skaters. The sitting height/stature (SH/ST) ratio is significantly lower in
      pre-elite skaters, while elite and test stream skaters do not differ in this
      indicator of proportions. Free skaters are taller and heavier; have a higher body
      mass index (BMI), limb circumferences and sum of skinfolds; and proportionally
      shorter legs than dancers and pair skaters. Free skaters, dancers and pair
      skaters, however, do not differ in somatotype. CONCLUSIONS: The results suggest
      that figure skating favors lightness, leanness, higher mesomorphy and lower
      endomorphy at more elite levels. Shortness, leanness and linearity of physique
      appear to be selective factors associated with specialization in dance and pair
      skating.

PMID- 16446681
TI  - Exercise in a hot environment: comparison of two different fluid intake patterns.
AB  - AIM: Extensive research has been undertaken in the area of exercise and
      hydration. Most work has focused on prehydration. Less is known about different
      fluid intake patterns during exercise and its effect in thermoregulatory
      variables in hot environments. This study attempted to determine if ingesting
      fluid either in a single bolus or intermittently during exercise had different
      results in thermoregulatory parameters and thirst in a hot environment. METHODS:
      Six moderately trained men and women (n=6, 5 male, 1 female; mean+/-SD: age
      28.5+/-2.5 y; weight 74.4+/-3.3 kg, VO2max 45.9+/-3.7 ml.kg.min-1) completed 2
      exercise sessions in a randomized, counterbalanced order. Treatment 1 (bolus)
      consisted of 60 minutes of bicycling at 50% of VO2max in a climatic chamber (dry
      bulb temperature, 35 degrees C, 45% relative humidity). Subjects consumed 1 000
      ml of plain cool (22 degrees C) water immediately before exercise. During
      treatment 2 (intermittent) the same environmental conditions were present, but
      subjects consumed 250 ml of water immediately before exercise. During the bicycle
      ride, subjects consumed 250 ml of cool water at minutes 15, 30, and 45 of
      exercise for a total trial volume of 1,000 ml. Tympanic ear temperatures, heart
      rates, rating of perceived exertion (RPE), and thirst scale data were collected
      immediately before exercise and at minutes 10, 20, 30, 40, 50, and 60 of
      exercise. RESULTS: No statistical differences were noted in temperature between
      treatments (P>0.05). Lower heart rates and thirst scores were noted for the bolus
      treatment at various time points (P<0.05). Little differences were noted between
      treatments for RPE during exercise. CONCLUSIONS: These results suggest that
      consumption of water in a single bolus is more beneficial for some aspects of
      thermoregulatory control and delaying thirst during exercise in the heat.
      Additional mechanistic studies with larger sample sizes are warranted.

PMID- 16446682
TI  - The effects of creatine supplementation on performance during the repeated bouts
      of supramaximal exercise.
AB  - AIM: The aim of this study was to investigate the effects of creatine
      supplementation on performance during the repeated bouts of supramaximal
      exercise. METHODS: Twenty-three untrained young males participated in the study.
      A double blind design was used to create the creatine and placebo groups. Wingate
      test was performed 5 times with 90 g x kg(-1) body weight load with 2-min
      intervals. Peak power, mean power (MP), fatigue index (FI) were calculated.
      Capillary blood samples for lactate analysis were taken during the initial rest
      period and soon after the fifth Wingate test. For 6 days the creatine group
      (n=12) ingested 5 g creatine monohydrate, the placebo group (n=11) a flavored
      drink without creatine monohydrate 4 times daily. On the 7th day, the Wingate
      tests were repeated, as was the 1st day. RESULTS: In the creatine group, MP in
      the 3rd and 4th Wingate test, in the placebo group FI in the 1st and 2nd Wingate
      test significantly increased. While the total power output obtained from the five
      Wingate tests increased 7.6% from 366.3+/-65 W to 394+/-67.1 W, there was no
      change in the placebo group. CONCLUSIONS: It is concluded that creatine
      supplementation enhances total power output during the repeated bouts of
      supramaximal exercise separated by short resting intervals.

PMID- 16446683
TI  - Differences in skinfold thicknesses and fat distribution among top-class runners.
AB  - AIM: The purpose of this research was to determine skinfolds values in male and
      female top-class runners who competed in different distances in order to identify
      the association of sex and event with fatness and distribution of subcutaneous
      fat. METHODS: Eight skinfolds were measured on male (n=130) and female (n=56) top
      class runners. Sum of 6 skinfolds and extremity/trunk fat ratio was calculated.
      Runners were distributed into groups according to the event in which they
      obtained their best performance. RESULTS: The skinfolds values found in our
      athletes were very low. Female runners obtained higher values in extremity
      skinfolds than male runners; the differences in chest, biceps and abdominal
      skinfolds are only significant in short duration events; no differences were
      found in suprailiac and subscapular skinfolds. In both sexes, all skinfolds
      showed significantly lower values among marathon runners; no differences were
      found in skinfolds values among runners competing in distances ranging from 100 m
      to 10,000 m. Extremity/trunk fat ratio was not related to event. CONCLUSIONS: The
      lower skinfold values found in all groups of runners may be due to a high
      performance; this analysis shows that a slight excess of fat is not beneficial in
      order to obtain a high performance in any distance. Fatness is only associated to
      marathon events, probably due to the fact that these runners are engaged in
      higher training volume and that only in this event fat metabolism prevails in
      training and competition. Distribution of subcutaneous fat may be more dependent
      on biological or environmental factors unrelated to type of training.

PMID- 16446684
TI  - Prediction of segmental percent fat using anthropometric variables.
AB  - AIM: This study aimed to develop a prediction equation for segmental percent fat
      from anthropometric measurements. METHODS: The subjects were 107 adults,
      consisting of 77 males and 30 females, aged from 21 to 82 years. Height, weight,
      waist circumference, hip circumference, body mass index, waist hip ratio and
      subcutaneous fat thickness (SFT) were used as anthropometric measurements. The
      SFTs were measured at 14 sites. Segmental percent fats in both arms (%SF(arms)),
      both legs (%SF(legs)) and trunk (%SF(trunk)) were measured by dual-energy
      absorptiometry (DXA) method, and these values were used as references. To predict
      the segmental percent fat measured by DXA, stepwise multiple regression analysis
      was conducted using sex, age and the anthropometric measurements as predictors.
      To examine the systematic error between the observed and predicted values, the
      error and the observed values were plotted based on Bland-Altman technique, and
      limits of agreement (LA) were also calculated. RESULTS: The R, SEE and range of
      LA values in each prediction equation was as follows: %SF(arms): R=0.919,
      SEE=3.333%, LA=6.5%; %SF(legs): R=0.915, SEE=3.468, LA=6.5%; %SF(trunk): R=0.858,
      SEE=4.944, LA=9.7%. These prediction equations used 5 to 7 predictors and met the
      necessary standards for predicting body fat. Although the prediction accuracy of
      %SF(trunk) was inferior than those of %SF(arms) and %SF(legs), it was superior to
      those found in previous study reports predicting abdominal visceral fat mass and
      fat mass at the trunk from anthropometric measurements. CONCLUSIONS: These
      prediction equations can be considered useful and practical for predicting
      segmental percent fat and assessing body fat distribution.

PMID- 16446685
TI  - Soy intake plus moderate weight resistance exercise: effects on serum
      concentrations of lipid peroxides in young adult women.
AB  - AIM: Exercise can conceivably increase concentrations of lipid peroxides (by
      producing oxidant stress) or decrease their concentrations (by accelerating
      peroxide breakdown). The net effect could depend on exercise intensity and
      nutritional antioxidant intake. METHODS: Recreationally trained, young adult
      women (n=18) consumed antioxidant-rich soy protein or antioxidant-poor whey
      protein for 4 weeks (40 g protein/day). A moderate intensity, weight resistance
      exercise session was done before and after the 4 week period. Blood was drawn
      before each exercise session and postexercise at 0, 3 and 24 h. Serum from the
      pre-exercise draw was analyzed for antioxidant status (based on radical
      scavenging capacities); serum from pre- and postexercise draws were analyzed for
      concentrations of lipid peroxides as well as creatine kinase activities (which
      are affected by oxidant damage to muscles). RESULTS: Soy, but not whey intake,
      increased pre-exercise serum antioxidant status values and inhibited exercise
      induced increases in creatine kinase activities. Before soy or whey intake, serum
      values for lipid peroxides rose at two of the three postexercise times. After
      whey intake, values for lipid peroxides showed no increase at the three
      postexercise times. After soy treatment, values for lipid peroxides actually
      showed a decrease at the three postexercise times. CONCLUSIONS: Moderate
      intensity exercise exerted variable effects on serum lipid peroxides with
      decreases occurring with 4 weeks of soy intake, which also produced other
      antioxidant effects.

PMID- 16446686
TI  - B-type natriuretic peptide in athletes performing an Olympic triathlon.
AB  - AIM: Brain natriuretic peptide (BNP) is a cardioactive molecule produced in the
      myocardium. BNP is a sensitive marker of cardiac failure and its measurement in
      blood could be useful to the diagnosis and the treatment of this disease.
      Sporting activities, especially endurance ones, can induce cardiac problems,
      owing to the high workload for the myocardium during long and ultralong heavy
      effort. There are 2 papers describing the behavior of BNP in endurance events.
      BNP was elevated in marathoners, immediately after the race and also after 4 h.
      We studied the behavior of BNP in the triathlon, which is a complex sport
      characterized by 3 different activities (swimming, cycling, running). METHODS: We
      recruited 49 athletes, all males, except for 4 females; 2 athletes did not finish
      the race and were not included in the statistical analysis in 2 different
      competitions. In these subjects we measured BNP using an immunological method
      before and after a triathlon. RESULTS: No statistical significance between BNP
      values, before and after the triathlon, was found. CONCLUSIONS: We found no
      significant differences between pre- and postcompetition BNP values. Moreover,
      the range of values in both the blood drawings are similar of those of the
      general population, representing the biological variability of the analyte. The
      values in regularly trained athletes,, are not different from the general
      population and BNP is not modified by a triathlon, a typical endurance sport
      performance. We can underline that BNP increases in plasma are induced by heavy
      pathologies and are not influenced by physical activities, even strenuous ones.

PMID- 16446687
TI  - Sudden cardiac death due to physical exercise in male competitive athletes. A
      report of six cases.
AB  - In the period of 30 years, i.e. from 1973 to 2002, we noticed in Croatia 6 sudden
      and unexpected cardiac deaths in male athletes during or after training. Two were
      soccer players, 2 athletic runners, one was a rugby player and one was a
      basketball player. All of them were without cardiovascular symptoms. At the
      forensic autopsy, the first athlete, aged 29, had chronic myocarditis and
      thickened left ventricular wall of 15 mm. The second, aged 21, had an acute
      myocardial infarction of the posterior wall with normal coronaries and thickened
      left ventricular wall of 15 mm. The third aged 17, had hypoplastic right coronary
      artery and narrowed ascending aorta, suppurant tonsillitis and subacute
      myocarditis. Two athletes, aged 29 and 15, had hypertrophic cardiomyopathy and
      normal coronaries, and one dilated aorta. The sixth, aged 24, had arrhythmogenic
      cardiomyopathy of the right ventricle. All the 6 athletes died suddenly,
      obviously because of malignant ventricular arrhythmias. In Croatia the death rate
      among athletes reached 0.15/100 000, in others who practice exercise reached
      0.74/100,000 and the difference is highly significant (c2=14.487, Poisson
      rates=3.81, P=0.00014) and in physicians-specialists reached 33.6/100,000.
      Preventive medical examinations are essential, especially in athletes before
      physical exercise, as are other investigations in every case suspicious of heart
      disease, including electrocardiogram (ECG), stress ECG, echocardiography and
      stress-echocardiography and other findings if indicated. Physical exercise is
      contraindicated in acute respiratory infection: in 2 of those cases had been a
      cause of death as a trigger.

PMID- 16446688
TI  - Body weight satisfaction and weight loss attempts in fitness activity involved
      women.
AB  - AIM: The aim of the present study was to determine the attitude of women involved
      in fitness physical activity (PA) towards weight loss and to find out factors
      that may possibly lead to weight loss behaviors. METHODS: The study sample
      consisted of 352 women involved in recreational PA in health and fitness clubs.
      Participants filled a questionnaire that was designed to assess weight related
      aspects of body image, dieting prior to PA, PA motivation, exercise experience,
      frequency and instructor's encouragement to go on diet. The relative incidence of
      weight loss behavior and emotional weight related state across age (<22 years, 22
      31 years, >31 years), body mass index (BMI), exercise experience groups (>2
      years, <2 years) was tested by use of c2 analysis. Multivariate logistic
      regression analysis was used to estimate the dependence of variables that can
      trigger the drive to lose weight. RESULTS: The greater dissatisfaction with the
      body weight was related with the younger age, while younger age did not predicted
      current dieting. Higher than normal BMI predicted overeating behavior. Lowest BMI
      (less than 18.5) was related with higher overestimation of body weight. PA
      experience was related with higher body shape satisfaction. Weight control
      related dieting prior to PA predicted negative feelings about weight gain and
      current weight related dieting. Obligatory body shape improvement motivation was
      related to more negative feelings of weight control. Sport instructor's
      encouragement to go on diet predicted dieting and overeating. CONCLUSIONS: The
      strongest predictors of weight loss behavior were obligatory motivation to
      improve body shape through exercising, dieting prior to PA and instructors'
      encouragement to go on a diet.

PMID- 16446689
TI  - Self-reported health, physical activity and prevalence of complaints in elite
      cross-country skiers and matched controls.
AB  - AIM: The purpose of this study was to compare physical health, physical activity
      and location for possible symptoms in high school students with cross-country
      skiers of the same age from ski high schools. Another aim was to study back pain
      with regards to influence on skiing. METHODS: The subjects studied were: 92%
      (n=120) of all Swedish cross-country skiers at ski high schools and 68% (n=993)
      of regular high school students from the North part of Sweden answered a reliable
      questionnaire (r=1) with regards to health, physical activity and location of
      possible symptoms/injuries during the last 3 months. Furthermore, the skiers
      answered questions on possible ski related back pain. RESULTS: All skiers were
      active also in other sports compared with 26% of the controls and at considerably
      higher levels of physical effort than the controls; 92% of the skiers and 76% of
      the controls described themselves as healthy, meaning ''very good'' or ''good''
      (P=0.0001); 55% of the skiers and 64% of the controls reported recent symptoms
      (P=0.06); 47% of the skiers reported previous or present complaints of back pain,
      mainly low back pain, which could be relieved by changing body position from a
      flexed to a more extended one while skiing, and 77% reported their back pain to
      disappear during rest. CONCLUSIONS: These results show the need for encouraging
      regular high school students to participate in sport. It also shows the
      importance of introducing preventative strategies regarding back pain to long
      distance cross-country skiers, who are exposed to a prolonged flexed position of
      their back.

PMID- 16446691
TI  - Quantification of relationship between health status and physical fitness in
      middle-aged and elderly males and females.
AB  - AIM: The purpose of this study was to quantify the degree of the relationship
      between health status and physical fitness level in middle-aged and elderly
      people using multiple discriminant analysis. METHODS: The participants were 3114
      males and females aged 30 to 69 years. Ten physical fitness tests and medical
      checkups were performed. The participants were divided into 2 groups according to
      health status; the healthy group and the unhealthy group. Multiple discriminant
      analysis was applied to the multivariate data. RESULTS: Correct discriminant
      probabilities of multiple discriminant functions to discriminate the healthy
      group and unhealthy group were 72.3% for males and 71.7% for females. For all age
      groups, a gender difference was not found (P>0.05). For aging, as a result of the
      test of proportion, it was found that the correct discriminant probabilities
      decreased with age for both genders (P<0.05). CONCLUSIONS: These results suggest
      that there is a relatively strong relationship between health status and the
      level of physical fitness in both males and females. These findings support daily
      physical activities and exercise to maintain or improve physical fitness could be
      useful for the health status of middle-aged and elderly people. From the result
      that the correct discriminant probability decreased with age, the changes in
      probability for males and females were calculated and described with correct
      discriminant probabilities by moving averages with 5 point smoothing.

PMID- 16446690
TI  - The effects of chondroitin sulfate supplementation on indices of muscle damage
      induced by eccentric arm exercise.
AB  - AIM: Delayed onset of muscle soreness (DOMS) often results from unaccustomed
      exercise or exercise that involves heavy eccentric loading of skeletal muscle.
      Chondroitin sulfate (CS) has been reported to possess anti-inflammatory and
      analgesic properties and has been used widely in the treatment of osteoarthritis.
      Based on these findings, the investigators sought to determine whether CS
      supplementation might reduce DOMS symptoms associated with eccentric arm
      exercise. METHODS: Sixteen non-resistance-trained males participated in a double
      blind protocol. Subjects consumed 3,600 mg x day-1 of encapsulated CS or placebo
      for 14 days preceding the exercise protocol and during 48 hours of follow-up
      measurements. Subjects performed a maximum of 50 eccentric contractions of the
      elbow flexors against a resistance that was 120% of the concentric one-repetition
      maximum. RESULTS: Significant time effects were present for soreness, relaxed
      elbow extension (joint angle), and creatine kinase; all measures were
      significantly altered 48 hours after the exercise session. No effects were
      present for complement system fragment C3a and prostaglandin E2. No significant
      treatment or interaction effects were detected for any of the variables.
      CONCLUSIONS: CS supplementation was not found to be effective in the prevention
      of DOMS, nor did it influence biochemical indices of inflammation and muscle
      damage following heavy eccentric loading of the arm flexors.

PMID- 16446692
TI  - Resistance training in older women: effect on vertical jump and functional
      performance.
AB  - AIM: Few studies have determined the effects of a heavy resistance training on
      vertical jump performance in older adults. The purpose of the present study was
      to evaluate the effects of a 12 week heavy resistance training in vertical jump
      and functional performance in healthy, inactive, older women. METHODS: Seventeen
      sedentary older women (aged 53-69 years) were assigned either to a control (C,
      n=8), or to a heavy resistance training (RT, n=9). The RT group trained knee
      extensors and flexors at 80% of 1-repetition maximum (1-RM), 3 days per week for
      12 weeks. Both groups were evaluated in 1-RM lower body strength, squat jump (SJ)
      and countermovement jump (CMJ) height, and chair rising time, before and after
      the training period. RESULTS: After the training period, RT significantly
      improved (P<0.001) the 1-RM lower body strength, SJ, CMJ height, and chair rising
      by 68.9%, 24.5%, 21.7%, and 13%, respectively. Significant correlations were
      observed among the percent (%) change in 1-RM lower body strength and SJ
      (r=0.849, P<0.001), CMJ height (r=0.797, P<0.001), and chair rising time (r=
      0.917, P<0.001). CONCLUSIONS: Muscle power improved after a short-term heavy
      resistance training, as measured by vertical jump and chair rising performance,
      in inactive older adults. The gains in muscle strength may contribute to the
      gains in chair rising time, SJ and CMJ height.

PMID- 16446693
TI  - Coagulation parameters in senior athletes practicing endurance sporting activity.
AB  - AIM: Physical activity is practiced more and more by middle-aged people. We
      studied the behavior of the coagulation system before and after near-maximum,
      specific and standardized exercise tests in 2 groups of senior athletes. METHODS:
      The subjects of the study were 2 groups of athletes over 40 years of age (ranging
      41 to 60 years): 10 rowers and 10 marathon runners. The data were compared with
      10 controls (ranging in age from 40 to 71 years) tested on the cycle ergometer.
      The first group (rowers) was tested on a rowing machine; the second group
      (marathon runners) performed a maximal exercise on the treadmill. All subjects
      were tested to a maximal level of cardiovascular and muscular exertion and
      cardiac and respiratory parameters were monitored. The following coagulation
      tests were performed before and after maximal exercise: prothrombin time (PT),
      partial activated thromboplastin time (PTT), fibrinogen (FBG), antithrombin III
      (ATIII), protein C (PC), protein S (PS), prothrombin fragment 1+2 (F1+2), tissue
      activator of plasminogen (t-PA) and its inhibitor (PAI). All subjects performed a
      complete maximal specific test. RESULTS: The results showed all individuals
      produced a significant increase of FBG, PT and PTT activities and a lowering
      trend for PC and PS inhibitors after maximal exercise testing. ATIII levels
      increased significantly in trained subjects. After the test, data regarding
      fibrinolysis showed higher t-PA levels in athletes as compared with controls. PAI
      levels indicated a more marked decrease in athletes. The F1+2 showed a moderate
      but significant increase in the control group. CONCLUSIONS: Coagulative tests
      showed an increase in procoagulant and fibrinolysis parameters in all the groups
      but the increased fibrinolytic activity in trained athletes indicates a
      protective factor and greater vascular efficiency. The results demonstrate that
      sporting activity practiced by middle-aged people accelerates fibrinolytic
      activity in conditioned subjects. In conclusion, physical activity benefits the
      coagulation system particularly as regards fibrinolysis.

PMID- 16446694
TI  - An approach to verifying delayed menarche in Japanese female athletes. Analysis
      by wavelet interpolation method.
AB  - AIM: The theory of delayed menarche in female athletes, despite some evidence for
      such a delay, has not yet been verified. We examined a means to verify this
      hypothesis by comparing ages at menarche and at peak height velocity (PHV)
      derived from the wavelet interpolation method (WIM) for female athletes and non
      athletes (control group). METHODS: We identified age at maximum peak velocity as
      the index of the physical maturation rate by WIM. We then conducted a study
      involving 144 female athletes in their 1st year at University in the Tokai area,
      all of whom had competed in a national high school sports competition (athlete
      group). Past school records of these subjects' heights from the 1st grade of
      elementary to the 3rd year of senior high school (1984-1995) were collected, and
      ages at menarche were ascertained from questionnaires. A control group of 78 non
      athletes was similarly examined. RESULTS: This difference (interval) between age
      at menarche and age at PHV was 1.62 years (SD=1.25) in the athlete group and 1.08
      years (SD=0.74) in the control group. The difference between the 2 groups was
      statistically significant (P<0.01). This finding provides evidence that menarche
      in female athletes is delayed in relation to physical maturation rate.
      CONCLUSIONS: This result alone cannot establish whether athletic training is the
      only cause of this delay; however, an approach to verifying the hypothesis of
      delayed menarche in female athletes has been established by this finding.

PMID- 16446696
TI  - Use of acetaminophen in young subelite athletes.
AB  - AIM: The purpose of the present investigation was to look for other drugs besides
      doping substances in the urine of subelite athletes submitted to heavy training.
      METHODS: One hundred and forty-one young subelite athletes (in sprint, cycling,
      middle distance running and handball) were included in the study, with a control
      group of 89 high school pupils. Drugs were researched by high performance liquid
      chromatography using a diode array detector. RESULTS: Among the 212 subjects who
      agreed to give a urine sample, acetaminophen was detected: 9.5% for the subelite
      athletes versus 1.3% for the control group with a greater difference for sprint
      and cycling training (26.7% and 20%, respectively). Acetaminophen is used to
      treat both acute and chronic pains. It relieves pain by elevating the pain
      threshold. CONCLUSIONS: The use of acetaminophen has to be taken into account by
      medical staff, trainers and educators.

PMID- 16446697
TI  - Gene expression profile of cultured adult compared to immortalized human RPE.
AB  - PURPOSE: ARPE19 is a spontaneously immortalized cell line of human retinal
      pigment epithelium (RPE) that is used widely to draw inferences about the
      behavior of adult human RPE (ahRPE). We used DNA microarray analysis to compare
      the gene expression profiles of these two cell types. METHODS: Second-passage
      cultured ahRPE from four human donors (age range 48-82 years) and ARPE19 cultured
      to confluence in five dishes were used for this DNA microarray study. Total RNA
      was isolated and first- and second-strand complimentary DNA was synthesized using
      standard techniques. Biotin-labeled antisense complimentary RNA was produced by
      an in vitro transcription reaction. Target hybridization, washing, staining, and
      scanning probe arrays were done following an Affymetrix GeneChip Expression
      Analysis Manual. Microarray data were normalized and statistical techniques were
      used to determine the presence or absence of expression of individual genes
      within ARPE19 and ahRPE, and their relative expression levels. RESULTS:
      Hierarchic clustering analysis demonstrated that the gene expression profile of
      ahRPE and ARPE19 samples cluster into two distinct groups with no discernable
      overlap. The expression of 5,634+/-65 gene probes (out of 12,600 on microarray
      Human U95Av2 chip) was detected in ARPE19 cells compared to 5,580+/-84 genes in
      ahRPE cells from four human donor eyes. Thirty-five genes are expressed
      exclusively in ahRPE and nine genes exclusively in ARPE19 cells. Fifty additional
      genes have a threefold increase and 40 genes have a threefold decrease in
      expression level in ahRPE compared to ARPE19. There was no clear difference in
      the global expression level of genes known to be related to phagocytosis,
      angiogenesis, or apoptosis. CONCLUSIONS: There are significant differences in the
      gene expression profile of ahRPE compared to ARPE19, and with some genes
      exclusively being expressed in one group and other genes being upregulated or
      downregulated by threefold. Caution should be exercised when generalizing results
      obtained from ARPE19 to the behavior of ahRPE.

PMID- 16446695
TI  - Sex differences in knee joint laxity change across the female menstrual cycle.
AB  - AIM: To elucidate the hormonal influences on sex differences in knee joint
      behavior, normal-menstruating females were compared to males on serum hormone
      levels and anterior knee joint laxity (displacement at 46N, 89N and 133N) and
      stiffness (Linear slope of deltaForce/deltaDisplacement for 46-89N and 89-133N)
      across the female menstrual cycle. METHODS: Twenty-two females were tested daily
      across one complete menstrual cycle, and 20 males were tested once per week for 4
      weeks. Five days each representing the hormonal milieu for menses, the initial
      estrogen rise near ovulation, and the early and late luteal phases (total of 20
      days) were compared to the average value obtained from males across their 4 test
      days. RESULTS: Sex differences in knee laxity were menstrual cycle dependent,
      coinciding with significant elevations in estradiol levels. Females had greater
      laxity than males on day 5 of menses, days 3-5 near ovulation, days 1-4 of the
      early luteal phase and days 1, 2, 4 and 5 of the late luteal phases. Within
      females, knee laxity was greater on day 5 near ovulation compared to day 3 of
      menses, and days 1-3 of the early luteal phase compared to all days of menses and
      day 1 near ovulation. On average, differences observed between sexes were greater
      than those within females across their cycle. There were no differences in
      anterior knee stiffness between sexes or within females across days of the
      menstrual cycle.

PMID- 16446699
TI  - A missense mutation in the gammaD-crystallin gene CRYGD associated with autosomal
      dominant congenital cataract in a Chinese family.
AB  - PURPOSE: To identify the genetic defect in autosomal dominant congenital
      cataracts in a six generation Chinese family. METHODS: Clinical and
      ophthalmological examinations were performed on the affected and unaffected
      family members. All the members were genotyped with microsatellite markers at
      loci which were considered to be associated with cataracts. A two-point LOD score
      was calculated using the Linkage package after genotyping. A mutation was
      detected by direct sequencing using gene specific primers. RESULTS: Clinical
      heterogeneity was observed within this family, three affected individuals showed
      nuclear cataract and others had coralliform cataracts. Significant evidence of
      linkage was obtained at markers D2S325 (LOD score [Z]=3.10, recombination
      fraction [theta]=0.0) and D2S1782 (Z=5.97, theta=0.0), respectively. Haplotype
      analysis indicated that the cataract gene was close to those two markers.
      Sequencing of the gammaD-crystallin gene (CRYGD) revealed a C>T transition in
      exon 2, that causes a conservative substitution of Arg to Cys at codon 14 (R14C).
      This mutation co-segregated with all affected individuals and was not observed in
      unaffected or 100 normal unrelated individuals. Bioinformatic analyses also
      showed that a highly conserved region was located at Arg14. CONCLUSIONS: This
      study is the first reported case with phenotype of coralliform/nuclear cataract
      that associated with the mutation of Arg14Cys (R14C) CRYGD.

PMID- 16446698
TI  - Fibroblast growth factor receptor 1 (Fgfr1) is not essential for lens fiber
      differentiation in mice.
AB  - PURPOSE: The developing lens expresses at least three different FGF receptor
      genes (Fgfr1, Fgfr2, Fgfr3). Furthermore, FGFs have been shown to induce lens
      epithelial cells to differentiate into fiber cells both in vitro and in vivo.
      While the loss of Fgfr2 alone does not prevent fiber differentiation and the loss
      of Fgfr3 alone does not appear to affect lens development, the independent role
      of Fgfr1 in lens development has not been reported. These experiments were
      conducted to determine if Fgfr1 plays an independent, essential role in lens
      development. METHODS: To address this question, we took two complementary
      approaches. First, we employed the aphakia (ak) lens complementation system to
      show that Fgfr1 deficient embryonic stem (ES) cells were able to form a normal
      embryonic lens that maintains a normal pattern of crystallin gene expression.
      Second, we employed the Cre-loxP system to achieve lens-specific inactivation of
      Fgfr1. RESULTS: Fgfr1 null embryonic stem cells were able to rescue normal
      embryonic lens development in chimeric combination with aphakia mutant embryos.
      In addition, conditional deletion of Fgfr1 does not compromise lens development
      either before or after birth. CONCLUSIONS: The results of both approaches suggest
      that lens epithelial cell integrity, cell cycle regulation and lens fiber
      differentiation are intact in the Fgfr1 deficient lens. Overall, our results
      demonstrate that Fgfr1 is not cell autonomously essential for lens development
      and suggests functional redundancy among different FGF receptor genes with
      respect to lens fiber differentiation.

PMID- 16446701
TI  - The effect of insulin and glucose levels on retinal glial cell activation and
      pigment epithelium-derived fibroblast growth factor-2.
AB  - PURPOSE: The diabetic retina exhibits decreases in endogenous nonangiogenic
      neurotrophins. This study hypothesized that deficiencies in systemic and retinal
      pigment epithelium-derived (RPE) neurotrophic factors also influence retinal
      changes in diabetes. METHODS: Diabetes was established in Listar hooded rats with
      streptozotocin. Reverse transcriptase coupled polymerase chain reaction (RT-PCR)
      and immunoblotting were used to determine the expression of fibroblast growth
      factor-2 (FGF-2) in the retina and RPE, and glial fibrillary acid protein (GFAP)
      in the retina. In addition, primary human RPE cultures and a transformed Muller
      cell line were used to determine the effect of insulin, glucose, and insulin-like
      growth factor (IGF) on the expression of these substances. RESULTS: FGF-2 and
      GFAP were increased in retina, but FGF-2 was decreased in the RPE of diabetic
      animals. Retinal GFAP correlated with RPE FGF-2 expression in these animals.
      Insulin produced a dose-dependent increase in FGF-2 in RPE cells and decrease in
      GFAP in Muller cells grown in 15 mM glucose. In 5 mM glucose, insulin had no
      effect on expression of either protein. Physiological levels of insulin inhibited
      changes induced by 15 mM glucose. The effect of 9 nM insulin on each culture was
      mimicked by 1 nM IGF, and blocked with an IGFR-1 inhibitor. CONCLUSIONS: It is
      suggested that decreased systemic insulin and high glucose levels contribute to
      decreased FGF-2 production in the RPE and increased glial cell activation in the
      diabetic retina. Addition of insulin and IGF act to reverse this effect through
      the IGFR-1. These mechanisms may contribute to the development of diabetic
      retinopathy.

PMID- 16446700
TI  - Effects of VEGFR-1, VEGFR-2, and IGF-IR hammerhead ribozymes on glucose-mediated
      tight junction expression in cultured human retinal endothelial cells.
AB  - PURPOSE: To evaluate whether transfection of human retinal endothelial cells
      (HRECs) with plasmids expressing ribozymes designed to specifically cleave the
      mRNA and reduce expression of either vascular endothelial growth factor (VEGF)
      receptor-1 (VEGFR-1), or VEGF receptor-2 (VEGFR-2), or insulin-like growth factor
      I receptor (IGF-IR) modulates occludin expression in high glucose-treated cells.
      METHODS: Hammerhead ribozymes that specifically cleave the human VEGFR-1, VEGFR
      2, and IGF-IR mRNAs were developed and tested in vitro to determine ribozyme
      kinetics and cleavage specificity. HRECs grown in normal (5.5 mM) and high (25
      mM) glucose medium were transfected with plasmids expressing VEGFR-1, VEGFR-2, or
      IGF-IR hammerhead ribozymes. VEGF and IGF-I levels were measured in conditioned
      medium of HREC exposed to high glucose conditions, and the effect of varying
      glucose concentration on VEGFR-1 and VEGFR-2 phosphorylation was examined. The
      amount of the tight junction protein occludin was determined by western analysis,
      and the protein was localized by immunohistochemistry. RESULTS: Exposure of HRECs
      to high glucose resulted in increased VEGF and IGF-I expression as well as VEGFR
      2 but not VEGFR-1 phosphorylation. Immunocytochemistry and western analysis
      revealed that HRECs exposed to high glucose had reduced occludin staining and
      protein expression, respectively. Transfection of HRECs exposed to high glucose
      with either VEGFR-1, VEGFR-2, or IGF-IR hammerhead ribozymes prevented the
      downregulation of occludin protein expression. CONCLUSIONS: Our studies support
      that activation of VEGFR-1, VEGFR-2, and IGF-IR by high glucose contributes to
      disruption of tight junctions by decreasing occludin expression and may be
      important in the pathogenesis of blood-retinal barrier dysfunction in diabetic
      retinopathy.

PMID- 16446702
TI  - Microarray and protein analysis of human pterygium.
AB  - PURPOSE: Pterygium is a sunlight-related, ocular-surface lesion that can obscure
      vision. In order to identify specific genes that may play a role in pterygium
      pathogenesis, we analyzed the global gene expression profile of pterygium in
      relation to autologous conjunctiva. METHODS: Oligonucleotide microarray
      hybridization was used to compare the gene expression profile between human whole
      pterygium and autologous conjunctiva. Selected genes were further characterized
      by RT-PCR, western blot, and immunohistochemistry, and comparisons were made with
      limbal and corneal tissues. RESULTS: Thirty-four genes exhibited a 2 fold or
      greater difference in expression between human whole pterygium and autologous
      conjunctiva. Twenty-nine transcripts were increased and five transcripts were
      decreased in pterygium. Fibronectin, macrophage-inflammatory protein-4 (MIP-4),
      and lipocalin 2 (oncogene 24p3; NGAL) were increased 9, 5, and 2.4 fold,
      respectively, while Per1 and Ephrin-A1 were decreased 2 fold in pterygium.
      Western blots showed that fibronectin and MIP-4 were increased in pterygium
      compared to limbus, cornea, and conjunctiva. Immunohistochemical analysis showed
      fibronectin in the stroma; lipocalin 2 in the basal epithelial cells, basement
      membrane, and extracellular stroma; and MIP-4 in all areas of the pterygium.
      CONCLUSIONS: These data show both novel and previously identified extracellular
      matrix-related, proinflammatory, angiogenic, fibrogenic, and oncogenic genes
      expressed in human pterygium. Comparisons of selected genes with limbal and
      corneal tissues gave results similar to comparisons between pterygium and normal
      conjunctiva. The increased expression of lipocalin 2, which activates matrix
      metalloproteinases (MMP), is consistent with our previous findings that MMP-9 and
      other MMPs are highly expressed in pterygium basal epithelium.

PMID- 16446703
TI  - Hydrogen sulfide prevents apoptosis of human PMN via inhibition of p38 and
      caspase 3.
AB  - Hydrogen sulfide, together with carbon monoxide and nitric oxide, is now
      considered a gasotransmitter able to induce specific cellular responses. As
      hydrogen sulfide is a component of several natural compounds known to be
      effective in many inflammatory pathologies, particularly of the respiratory
      tract, we studied its effects in vitro on the survival and bactericidal activity
      of purified human neutrophils. We found that (1) HS(-) ions promote the survival
      of granulocytes, but not that of lymphocytes or eosinophils, cultured in serum
      free medium; (2) the pro-survival effect of HS(-) is due to inhibition of caspase
      3 cleavage and p38 MAP kinase phosphorylation; (3) the bactericidal activity of
      neutrophils is not impaired by hydrogen sulfide. We conclude that HS(-) promotes
      the short-term survival of neutrophils potentially accelerating the resolution of
      inflammatory processes and preventing the occurrence of new ones.

PMID- 16446704
TI  - Unlocking pathology archives for molecular genetic studies: a reliable method to
      generate probes for chromogenic and fluorescent in situ hybridization.
AB  - Chromogenic (CISH) and fluorescent (FISH) in situ hybridization have emerged as
      reliable techniques to identify amplifications and chromosomal translocations.
      CISH provides a spatial distribution of gene copy number changes in tumour tissue
      and allows a direct correlation between copy number changes and the morphological
      features of neoplastic cells. However, the limited number of commercially
      available gene probes has hindered the use of this technique. We have devised a
      protocol to generate probes for CISH that can be applied to formalin-fixed,
      paraffin-embedded tissue sections (FFPETS). Bacterial artificial chromosomes
      (BACs) containing fragments of human DNA which map to specific genomic regions of
      interest are amplified with phi29 polymerase and random primer labelled with
      biotin. The genomic location of these can be readily confirmed by BAC end pair
      sequencing and FISH mapping on normal lymphocyte metaphase spreads. To
      demonstrate the reliability of the probes generated with this protocol, four
      strategies were employed: (i) probes mapping to cyclin D1 (CCND1) were generated
      and their performance was compared with that of a commercially available probe
      for the same gene in a series of 10 FFPETS of breast cancer samples of which five
      harboured CCND1 amplification; (ii) probes targeting cyclin-dependent kinase 4
      were used to validate an amplification identified by microarray-based comparative
      genomic hybridization (aCGH) in a pleomorphic adenoma; (iii) probes targeting
      fibroblast growth factor receptor 1 and CCND1 were used to validate
      amplifications mapping to these regions, as defined by aCGH, in an invasive
      lobular breast carcinoma with FISH and CISH; and (iv) gene-specific probes for
      ETV6 and NTRK3 were used to demonstrate the presence of t(12;15)(p12;q25)
      translocation in a case of breast secretory carcinoma with dual colour FISH. In
      summary, this protocol enables the generation of probes mapping to any gene of
      interest that can be applied to FFPETS, allowing correlation of morphological
      features with gene copy number.

PMID- 16446705
TI  - Tumor-infiltrating T lymphocytes: friends or foes?
AB  - The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been a
      longstanding topic of debate. In cases where TILs have improved patient outcome,
      T lymphocytes are recognized as the main effectors of antitumor immune responses.
      However, recent studies have revealed that a subset of CD4(+) T cells, referred
      to as CD4(+)CD25(+) regulatory T cells (Treg), may accumulate in the tumor
      environment and suppress tumor-specific T-cell responses, thereby hindering tumor
      rejection. Hence, predicting tumor behavior on the basis of an indiscriminate
      evaluation of tumor-infiltrating T cells may result in inconsistent prognostic
      accuracy. The presence of infiltrating CD4(+)CD25(+) Treg may be detrimental to
      the host defense against the tumor, while the presence of effector T lymphocytes,
      including CD8(+) T cells and non-regulatory CD4(+) helper T cells may be
      beneficial. Enhanced recruitment of antitumor effector T lymphocytes to tumor
      tissue in addition to inhibition of local Treg, may therefore be an ideal target
      for improving cancer immunotherapy. This article reviews the antitumor functions
      of T-lymphocytes, with special attention given to CD4(+) regulatory T-cells
      within the tumor environment.

PMID- 16446707
TI  - Meth-DOP-PCR: an assay for the methylation profiling of trace amounts of DNA
      extracted from bodily fluids.
AB  - Cancer cells release their DNA into the patient's bodily fluids and cancer
      specific signatures can be recognized in the circulating DNA. The aberrant
      methylation of CpG-rich regions in gene promoter sequences is an early marker of
      cell transformation whose specificity and optimal sensitivity can be achieved by
      assessing the methylation status of multiple genes ('methylation profiling').
      Most of the current technologies for methylation analysis rely upon the
      combination of chemical conversion of the DNA and PCR analysis for the detection
      of methylated and unmethylated alleles. However, the small amount of circulating
      DNA, and its fragmentation, dramatically reduces the template DNA molecules
      making difficult the methylation profiling. To overcome this limitation, we have
      developed the Meth-DOP-PCR assay, a combination between a modified degenerate
      oligonucleotide primed PCR (DOP-PCR) and methylation-specific PCR (MSP), for the
      high-throughput methylation analysis of trace-amount of circulating DNA. We have
      demonstrated the concordance between Meth-DOP-PCR and MSP and shown the
      application of this technique for the methylation analysis of DNA extracted from
      the serum of lung cancer patients. We have estimated that through this procedure
      it is possible to obtain at least a 25-fold increase of the number of
      determinations allowing the methylation profiling from less than 1 ml of serum.
      Thus, Meth-DOP-PCR appears as a simple, cost-effective and efficient technique,
      for the development of novel methylation-based diagnostic assays.

PMID- 16446708
TI  - High throughput analysis of TCR-beta rearrangement and gene expression in single
      T cells.
AB  - Analysis of T-cell receptor beta chain (TCR-beta) rearrangement is essential to
      investigate T-cell responses in human autoimmune diseases, infection and cancer.
      Since the TCR-beta locus contains 55 variable (V) region gene segments, multiple
      assays have been necessary to determine TCR-beta rearrangements of individual T
      cells. We established a seminested rtPCR method for single T-cell analysis with
      two sets of degenerate primers covering 76 and 24% of the TCR-Vbeta genes,
      respectively. The specificity of the approach was validated by screening cDNAs
      obtained from T-cell clones (TCC) with defined TCR-beta rearrangement. We applied
      the method successfully to profile TCR-beta rearrangement of single T cells
      sorted from body fluids or dissected tissue. Concomitant analysis of other gene
      transcripts allowed determining phenotype and function of TCR-beta-defined single
      T cells. Our fast, cost-efficient and high throughput approach will facilitate
      studies on T-cell responses in human diseases.

PMID- 16446706
TI  - Lethal endotoxic shock using alpha-galactosylceramide sensitization as a new
      experimental model of septic shock.
AB  - The effect of alpha-galactosylceramide (alpha-GalCer) on lipopolysaccharide (LPS)
      mediated lethality was examined. Administration of LPS killed all mice pretreated
      with alpha-GalCer, but not untreated control mice. The lethal shock in alpha
      GalCer-sensitized mice was accompanied by severe pulmonary lesions with marked
      infiltration of inflammatory cells and massive cell death. On the other hand,
      hepatic lesions were focal and mild. A number of cells in pulmonary and hepatic
      lesions underwent apoptotic cell death. alpha-GalCer sensitization was
      ineffective for the development of the systemic lethal shock in Valpha14-positive
      natural killer T cell-deficient mice. Sensitization with alpha-GalCer led to the
      circulation of a high level of interferon (IFN)-gamma and further augmented the
      production of tumor necrosis factor (TNF)-alpha in response to LPS. The lethal
      shock was abolished by the administration of anti-IFN-gamma or TNF-alpha
      antibody. Further, the lethal shock did not occur in TNF-alpha-deficient mice.
      Taken together, alpha-GalCer sensitization rendered mice very susceptible to LPS
      mediated lethal shock, and IFN-gamma and TNF-alpha were found to play a critical
      role in the preparation and execution of the systemic lethal shock, respectively.
      The LPS-mediated lethal shock using alpha-GalCer sensitization might be useful
      for researchers employing experimental models of sepsis and septic shock.

PMID- 16446709
TI  - Dissecting the energetics of protein alpha-helix C-cap termination through
      chemical protein synthesis.
AB  - The alpha-helix is a fundamental protein structural motif and is frequently
      terminated by a glycine residue. Explanations for the predominance of glycine at
      the C-cap terminal portions of alpha-helices have invoked uniquely favorable
      energetics of this residue in a left-handed conformation or enhanced solvation of
      the peptide backbone because of the absence of a side chain. Attempts to quantify
      the contributions of these two effects have been made previously, but the issue
      remains unresolved. Here we have used chemical protein synthesis to dissect the
      energetic basis of alpha-helix termination by comparing a series of ubiquitin
      variants containing an L-amino acid or the corresponding D-amino acid at the C
      cap Gly35 position. D-Amino acids can adopt a left-handed conformation without
      energetic penalty, so the contributions of conformational strain and backbone
      solvation can thus be separated. Analysis of the thermodynamic data revealed that
      the preference for glycine at the C' position of a helix is predominantly a
      conformational effect.

PMID- 16446710
TI  - Introduction to the 2005 long course.
AB  - Dermatopathology, as with other fields of pathology, has undergone major changes
      in the last 25 years. Our understanding of epidermally derived neoplasms becomes
      far more advanced with each passing year. Evidence for this progress is readily
      apparent upon reviewing textbooks of dermatopathology over time and in examining
      the course contents of the long-course presentations at the United States
      Canadian Academy of Pathology annual meetings. What was once a simple discussion
      of melanocytic neoplasms (thought to be a variant of sarcoma) has become a
      reasonably complex analysis of the histologic, immunologic, and molecular aspects
      of melanocytic neoplasia. Similarly, our understanding of the development of
      cutaneous squamous cell carcinoma is greatly enhanced. The understanding of the
      molecular alterations that result in full transformation offers great insight
      into carcinogenesis. This introductory essay briefly traces this progression in
      setting the stage for the series of more detailed chapters about epidermal
      neoplasms that follow.

PMID- 16446711
TI  - Basal cell carcinoma: biology, morphology and clinical implications.
AB  - Basal cell carcinoma (BCC) is the most common malignant neoplasm of humans.
      Rising dramatically in incidence in North America, as likely reflects changing
      habits of the population and a move from more northerly climes to the sunbelt of
      the Southern and Southwestern United States, the incidence is surely to rise even
      higher in the future. The last decade has seen significant advances in our
      understanding of BCC biology and novel approaches to therapy, which hinge upon
      accurate diagnosis and subclassification by pathologists. The purpose of this
      review article is to summate the research advances in our understanding of BCC
      biology and to acquaint pathologists and clinicians to the practical issues in
      BCC diagnosis and subclassification which flow there from.

PMID- 16446712
TI  - Medicolegal aspects of neoplastic dermatology.
AB  - Medical malpractice litigation is rising at an explosive rate in the US and, to a
      lesser extent, in Canada. The impact of medical malpractice litigation on health
      care costs and the cost of insurance is dramatic. Certain specialist categories
      are becoming uninsurable in some parts of the US, while in others, clinicians are
      retiring early, restricting or changing practice or changing states of residence
      in consequence of medical malpractice claims and of the cost and availability of
      insurance. This, in turn, has had the real effect of denying care to patients in
      some communities in the US. Some 13% of all medical malpractice claims relate to
      one area of neoplastic dermatopathology, specifically, melanocytic neoplasia.
      Certain steps can be taken by pathology laboratories to reduce, but never
      completely eliminate, the risk of medical malpractice claims. In this review,
      attention is paid to the source of medical malpractice claims and an abbreviated
      approach to specific strategies for risk management is presented.

PMID- 16446713
TI  - The Spitzoid lesion: rethinking Spitz tumors, atypical variants, 'Spitzoid
      melanoma' and risk assessment.
AB  - Although much remains to be learned about Spitzoid lesions, there is increasing
      evidence that these tumors may be a type of melanocytic neoplasm distinct from
      conventional melanocytic nevi and malignant melanoma. In the current
      communication, the author has attempted to describe accurately the state-of-the
      art surrounding these lesions, their nomenclature, and assessment of risk.
      Acknowledging the peculiar nature of Spitzoid lesions, the author prefers the
      term Spitz tumor rather than 'Spitz nevus' (except perhaps for the most typical
      lesions) and argues against using the term 'Spitzoid melanoma' until more
      information is available to justify such a term. The author also believes that
      patients are best served by the comprehensive evaluation of Spitzoid lesions and
      their classification into three categories: (1) Spitz tumor without significant
      abnormality, (2) Spitz tumor with one or more atypical features (atypical Spitz
      tumor), including those judged to have indeterminate biological potential, and
      (3) malignant melanoma, rather than the two categories of 'Spitz nevus' and
      melanoma. Only rigorous characterization of sufficient numbers of Spitzoid
      lesions and long-term follow-up of patients will provide truly objective
      information for the formulation of optimal guidelines for the management of
      patients with these lesions.

PMID- 16446714
TI  - Histologic criteria for diagnosing primary cutaneous malignant melanoma.
AB  - Malignant melanoma accounts for the largest number of deaths attributed to skin
      cancer. It also provides the most diagnostic challenges for the histopathologist.
      This article, attempts to describe the histologic features most closely
      associated with the various growth patterns of the most common subtypes of
      melanoma. While it has been shown repeatedly that histologic subtypes likely
      provide clinicians and patients with minimal to no prognostic information, it is
      useful to separate these entities in order to elucidate the varied histologic
      features seen within the class of tumors known as melanoma. The discussion
      centers around a checklist of changes seen at the microscope that are associated
      with this diagnosis. The goal of this chapter is to provide the reader with one
      perspective on the series of changes that are used in order to establish (or
      exclude) a diagnosis of melanoma. There is a comprehensive literature that
      critically evaluates histologic parameters associated with this collection of
      tumors and relates them to prognostic information, and no attempt will be made to
      correlate the histologic change with prognostic information. This will be
      discussed in another chapter in this volume. Similarly, more esoteric subtypes of
      melanoma are characterized by histologic features that differ from the common
      types of melanoma and will be addressed in another chapter.

PMID- 16446715
TI  - Precursors to melanoma and their mimics: nevi of special sites.
AB  - Melanocytic nevi, which are benign tumors of melanocytes, may have occasional
      cosmetic significance but, for the most part, they are important only in relation
      to melanoma. Nevi are the most important simulants of melanoma, both clinically
      and histologically, and can usually be reliably distinguished from melanomas
      using published criteria. Some lesions are characterized by greater degrees of
      atypia and may be more difficult to diagnose. Dysplastic nevi are among the most
      important simulants of melanoma. Nevi may also be important as potential
      precursors of melanoma; however, most nevi are stable and will not progress to
      malignancy. Nevi are vastly more common than melanomas and the rate of
      progression of individual lesions is very low. Therefore, nevi are not as a rule
      managed by wholesale excision to prevent melanoma. Nevi are also important as
      risk markers, identifying individuals at greater risk of developing melanoma in
      the future. Dysplastic nevi and, to a lesser extent, common acquired and
      congenital nevi are among the most important melanoma risk markers. Nevi of
      special sites have been identified as nevi that may show atypical features
      suggestive of a dysplastic nevus or of a melanoma. However, they are not risk
      markers and they are not malignancies. Nevi of genital skin, acral skin, and
      flexural skin are among the most important 'nevi of special sites'. It is
      important, in considering the differential diagnosis of a lesion in a special
      site, to avoid overcalling such a lesion as a melanoma or a dysplastic nevus
      because this could lead to excessive treatment. Conversely, it is important to
      avoid undercalling a lesion that is a dysplastic nevus or a melanoma as a nevus
      of special sites, because in this circumstance a patient could lose the
      opportunity either for surveillance to recognize a developing melanoma at an
      early, curable stage, or for definitive treatment of an established malignancy.
      In this monograph, dysplastic nevi and nevi of special sites are compared and
      contrasted in relation to melanoma.

PMID- 16446716
TI  - Unusual variants of malignant melanoma.
AB  - A potential diagnostic pitfall in the histologic assessment of melanoma is the
      inability to recognize unusual melanoma variants. Of these, the more treacherous
      examples include the desmoplastic melanoma, the nevoid melanoma, the so-called
      'minimal-deviation melanoma,' melanoma with prominent pigment synthesis or
      'animal-type melanoma,' and the malignant blue nevus. Also problematic are the
      unusual phenotypic profiles seen in vertical growth phase melanomas; these
      include those tumors whose morphological peculiarities mimic cancers of
      nonmelanocytic lineage and those melanomas that express aberrant antigenic
      profiles not commonly associated with a melanocytic histogenesis. Metaplastic
      change in melanoma, balloon cell melanoma, signet-ring cell melanoma, myxoid
      melanoma, small cell melanoma and rhabdoid melanoma all have the potential to
      mimic metastatic and primary neoplasms of different lineage derivations. Abnormal
      immunohistochemical expression of CD 34, cytokeratins, epithelial membrane
      antigen, and smooth muscle markers as well as the deficient expression of S100
      protein and melanocyte lineage-specific markers such as GP100 protein (ie HMB-45
      antibody) and A103 (ie Melan-A) also present confusing diagnostic challenges. In
      this review, we will discuss in some detail certain of these novel
      clinicopathologic types of melanoma, as well as the abnormal phenotypic
      expressions seen in vertical growth phase melanoma.

PMID- 16446717
TI  - Prognosticators of melanoma, the melanoma report, and the sentinel lymph node.
AB  - Since the 1960s, the clinical characteristics of melanoma, its histopathology and
      its biological basis have been the subject of intense study at pigmented lesion
      clinics in North America, Europe, and Australia. More recently, the immense
      database of the Melanoma Committee of the American Joint Committee on Cancer
      (AJCC) has been exploited through complex mathematical models to measure the
      impact of various histologic features of primary melanomas and of sentinel lymph
      node deposits and to correlate these parameters with patient survival. The wealth
      of modern information available to pathologists and clinicians has become of
      vital interest to the prognostication of the individual patient with melanoma.
      The purpose of this review is to bring to the attention of anatomic pathologists
      the essential characteristics of the pathology report for primary cutaneous
      melanoma in the modern era.

PMID- 16446718
TI  - Squamous cell carcinoma: from precursor lesions to high-risk variants.
AB  - Cutaneous squamous cell carcinoma is second only to basal cell carcinoma in its
      incidence within our population. It is among the most common types of neoplasm
      afflicting the human race. Most cases are related to exposure to sunlight. This
      initial portion of the chapter will focus upon the biologic progression that
      results in the ultimate development of fully formed squamous cell carcinoma. The
      latter portion will focus upon the histologic features of squamous cell
      carcinoma, which may be potential prognostic indicators. While pathologists
      currently provide clinicians with information about many histologic features that
      may affect the outcome for patients with melanoma, there is little impetus for
      similar behavior on the part of pathologists when diagnosing squamous cell
      carcinomas. This is largely due to the relatively low metastasis rate for these
      tumors compared with melanomas; however, it may be possible for pathologists to
      separate out those squamous cell carcinomas with a higher chance for recurrence
      and metastasis. This chapter will examine many of these histologic features and
      propose a rationale for including this information in pathology reports.

PMID- 16446719
TI  - Malignant adnexal neoplasms.
AB  - Malignant cutaneous adnexal neoplasms are one of the most challenging areas of
      dermatopathology. Tumors of the pilosebaceous apparatus can occur as single
      lineage neoplasms or may manifest as complex proliferations with multilineal
      differentiation patterns including not only the germinative component of the hair
      bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct,
      but also the sweat duct components that relate to the apocrine secretory
      apparatus which empties into the follicle near the follicular bulge. Eccrine and
      apocrine neoplasms present a bewildering array of morphologies, which often defy
      precise classification. The purpose of this review is to discuss in detail the
      malignant neoplasms of the cutaneous adnexae and their benign and prognostically
      indeterminate mimics.

PMID- 16446727
TI  - Grants proposals and animal use protocols: is the IACUC playing by the rules?
      Instant replay' required.

PMID- 16446728
TI  - Grants proposals and animal use protocols: is the IACUC playing by the rules?

PMID- 16446729
TI  - Grants proposals and animal use protocols: is the IACUC playing by the rules?
      Modular doesn't apply.

PMID- 16446731
TI  - Grants proposals and animal use protocols: is the IACUC playing by the rules? A
      word from OLAW.

PMID- 16446730
TI  - Grants proposals and animal use protocols: is the IACUC playing by the rules?
      Don't ignore the proposal.

PMID- 16446732
TI  - What's your diagnosis? Lethargy and hind limb paralysis in a day-23 timed
      pregnant rat.

PMID- 16446734
TI  - Restraint collars. Part I: Elizabethan collars and other types of restraint
      collars.
AB  - Restraint collars can provide an investigator with a noninvasive means to prevent
      certain undesirable behaviors and provide a clinician with a nonpharmaceutical
      method to prevent an animal from inflicting self-injury; without proper use and
      monitoring, however, these collars can do more harm than good. This first part of
      our look at restraint collars introduces collar types and proper use. Next
      month's installment will review specific issues associated with the use of
      different types of collars for different species.

PMID- 16446735
TI  - Success of intracoelomic radiotransmitter implantation in the treefrog (Hyla
      versicolor).
AB  - Concern about the effects of habitat modification on the natural movements and
      behavior of amphibians has led researchers to devise several methods to follow
      individual animals as they migrate among seasonal resources; one such method is
      the surgical insertion of radiotransmitters. Intracoelomic implantation has come
      into general use despite the relative lack of specific procedural guidelines and
      information about the effects of transmitter insertion and removal. The author
      outlines the surgical implantation procedures used on a small amphibian (gray
      treefrog) and provides insight into the effects of multiple major surgical
      invasions on the long-term survival of amphibians. Multiple survival surgeries
      were successful in this study and may be an alternative to euthanasia in some
      instances.

PMID- 16446736
TI  - Experimental models of arteriogenesis: differences and implications.
AB  - Cardiovascular and cerebrovascular disease represent the two most common causes
      of mortality and morbidity in western countries, and the treatment for these is
      generally by the mechanical restoration of blood flow in the affected tissues.
      Stimulation of collateral artery growth (arteriogenesis) provides a potential
      alternative option for the treatment of patients suffering from occlusive artery
      disease. Therefore, researchers have established several angiogenesis and
      arteriogenesis animal models to investigate basic mechanisms and pharmacological
      modulation of collateral artery growth. The authors highlight the most important
      aspects of vascular growth, discuss different methods and techniques for
      examining the process, and review the advantages and disadvantages associated
      with the animal models available for studying this phenomenon.

PMID- 16446737
TI  - Use of the i-STAT portable clinical analyzer in mice.
AB  - The use of portable chemistry analyzers is an attractive option for obtaining
      clinical pathology panels in mice, because these analyzers require only small
      volumes of whole blood. However, in studies with other animals, portable
      analyzers do not always agree with results obtained using standard laboratory
      equipment. The authors evaluated the use of the i-STAT handheld portable clinical
      analyzer compared to the use of standard nonportable laboratory instruments in
      mice. As shown with other species, the i-STAT results did not always agree with
      standard laboratory instruments; however, the i-STAT does show reliability for
      certain chemistry assays.

PMID- 16446738
TI  - Searching for your ideal job?

PMID- 16446739
TI  - Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in
      depressive-like behavior.
AB  - Hormonal imbalances are involved in many of the age-related pathologies, as
      neurodegenerative and psychiatric diseases. Specifically, thyroid state
      alterations in the adult are related to psychological changes and mood disorders
      as depression. The dentate gyrus of the hippocampal formation undergoes
      neurogenesis in adult mammals including humans. Recent evidence suggests that
      depressive disorders and their treatment are tightly related to the number of
      newly born neurons in the dentate gyrus. We have studied the effect of thyroid
      hormones (TH) on hippocampal neurogenesis in adult rats in vivo. A short period
      of adult-onset hypothyroidism impaired normal neurogenesis in the subgranular
      zone of the dentate gyrus with a 30% reduction in the number of proliferating
      cells. Hypothyroidism also reduced the number of newborn neuroblasts and immature
      neurons (doublecortin (DCX) immunopositive cells) which had a severely
      hypoplastic dendritic arborization. To correlate these changes with hippocampal
      function, we subjected the rats to the forced swimming and novel object
      recognition tests. Hypothyroid rats showed normal memory in object recognition,
      but displayed abnormal behavior in the forced swimming test, indicating a
      depressive-like disorder. Chronic treatment of hypothyroid rats with TH not only
      normalized the abnormal behavior but also restored the number of proliferative
      and DCX-positive cells, and induced growth of their dendritic trees. Therefore,
      hypothyroidism induced a reversible depressive-like disorder, which correlated to
      changes in neurogenesis. Our results indicate that TH are essential for adult
      hippocampal neurogenesis and suggest that mood disorders related to adult-onset
      hypothyroidism in humans could be due, in part, to impaired neurogenesis.

PMID- 16446740
TI  - Polymorphism in the 5'-promoter region of serine racemase gene in schizophrenia.

PMID- 16446741
TI  - A direct androgenic involvement in the expression of human corticotropin
      releasing hormone.
AB  - We investigated the possibility of a direct action of androgens on the expression
      of the human corticotropin-releasing hormone (CRH), which plays a central role in
      the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and
      nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the
      paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen
      responsive element (ARE) in the human CRH promoter was subsequently analyzed with
      bandshifts and cotransfections in neuroblastoma cells. In the presence of
      testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression
      of AR in combination with testosterone repressed CRH promoter activity through
      the ARE. We conclude that androgens may directly affect CRH neurons in the human
      PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific
      pathogenesis of mood disorders.

PMID- 16446742
TI  - The brain-derived neurotrophic factor Val66Met polymorphism is associated with
      age-related change in reasoning skills.
AB  - A polymorphism (Val66Met) in the gene encoding brain-derived neurotrophic factor
      (BDNF) has previously been associated with impaired hippocampal function and
      scores on the Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS
      R). Despite its widespread expression in the brain, there have been few studies
      examining the role of BDNF on cognitive domains, other than memory. We examined
      the association between BDNF Val66Met genotype and non-verbal reasoning, as
      measured by Raven's standard progressive matrices (Raven), in two cohorts of
      relatively healthy older people, one aged 79 (LBC1921) and the other aged 64
      (ABC1936) years. LBC1921 and ABC1936 subjects had reasoning measured at age 11
      years, using the Moray House Test (MHT), in the Scottish Mental Surveys of 1932
      and 1947, respectively. BDNF genotype was significantly associated with later
      life Raven scores, controlling for sex, age 11 MHT score and cohort (P = 0.001).
      MHT, Verbal Fluency and Logical Memory scores were available, in later life, for
      LBC1921 only. BDNF genotype was significantly associated with age 79 MHT score,
      controlling for sex and age 11 MHT score (P = 0.016). In both significant
      associations, Met homozygotes scored significantly higher than heterozygotes and
      Val homozygotes. This study indicates that BDNF genotype contributes to age
      related changes in reasoning skills, which are closely related to general
      intelligence.

PMID- 16446743
TI  - Development of overweight in an atherosclerosis prevention trial starting in
      early childhood. The STRIP study.
AB  - CONTEXT: Recent data indicate a marked increase in the prevalence of obesity
      among school-aged children. Thus, efficacious programmes that prevent overweight
      development in children are urgently needed. OBJECTIVE: To evaluate the impact of
      repeatedly given, individualised dietary and lifestyle counselling on the
      prevalence of overweight during the first 10 years of life. DESIGN AND
      PARTICIPANTS: This study was a part of the Special Turku Coronary Risk Factor
      Intervention Project for Children (STRIP), which is a prospective, randomised
      trial aimed at reducing the exposure of the intervention children to the known
      risk factors of atherosclerosis. At the child's age of 7 months, 1062 children
      were assigned to an intervention group (n=540) or to a control group (n=522). The
      intervention children received individualised counselling focused on healthy diet
      and physical activity biannually. Height and weight of the children were measured
      at least once a year. MAIN OUTCOME MEASURE: Prevalence of overweight and obesity
      among the intervention and control children by sex and age. Children were
      classified as overweight or obese if their weight for height was >20% or > or
      =40% above the mean weight for height of healthy Finnish children, respectively.
      RESULTS: After the age of 2 years, there were continuously fewer overweight girls
      in the intervention group than in the control group. At the age of 10 years,
      10.2% of the intervention girls and 18.8% of the control girls were overweight
      (P=0.0439), whereas 11.6% of the intervention boys and 12.1% of the control boys
      were overweight (P approximately 1.00). Only three children in the intervention
      group were obese at some age point, whereas 14 control children were classified
      as obese at some age point. CONCLUSION: Individualised dietary and lifestyle
      counselling given twice a year since infancy decreases prevalence of overweight
      in school-aged girls even without any primary energy restrictions.

PMID- 16446745
TI  - Addition of aerobic exercise to dietary weight loss preferentially reduces
      abdominal adipocyte size.
AB  - OBJECTIVE: To determine if hypocaloric diet, diet plus low-intensity exercise,
      and diet plus high-intensity exercise differentially influence subcutaneous
      abdominal and gluteal adipocyte size in obese individuals. DESIGN: Longitudinal
      intervention study of hypocaloric diet, diet plus low-intensity exercise, and
      diet plus high-intensity exercise (calorie deficit = 2800 kcal/week, 20 weeks).
      SUBJECTS: Forty-five obese, middle-aged women (BMI = 33.0+/-0.6 kg/m2, age = 58+/
      1 years). MEASUREMENTS: Body composition testing and adipose tissue biopsies were
      conducted before and after the interventions. Subcutaneous abdominal and gluteal
      adipocyte size was determined. RESULTS: All three interventions reduced body
      weight, fat mass, percent fat, and waist and hip girths to a similar degree. Diet
      only did not change subcutaneous abdominal adipocyte size, whereas both diet plus
      exercise groups significantly reduced abdominal adipocyte size. Changes in
      abdominal adipocyte size in the diet plus exercise groups were significantly
      different from that of the diet group. Gluteal adipocyte size decreased similarly
      in all three groups. CONCLUSION: Addition of exercise training to dietary weight
      loss preferentially reduces subcutaneous abdominal adipocyte size in obese women.
      This may be of importance for the treatment of health complications associated
      with subcutaneous abdominal adiposity.

PMID- 16446744
TI  - Japanese men have larger areas of visceral adipose tissue than Caucasian men in
      the same levels of waist circumference in a population-based study.
AB  - Visceral adipose tissue (VAT) is an independent risk factor for metabolic and
      cardiovascular disorders. There has been no study that demonstrated different
      abdominal fat distribution between Asian and Caucasian men. As the Japanese are
      less obese but more susceptible to metabolic disorders than Caucasians, they may
      have larger VAT than Caucasians at similar levels of obesity. We compared the
      abdominal fat distribution of the Japanese (n=239) and Caucasian-American (n=177)
      men aged 40-49 years in groups stratified by waist circumference in a population
      based sample. We obtained computed tomography images and determined areas of VAT
      and subcutaneous adipose tissue (SAT). We calculated VAT to SAT ratio (VSR). The
      Japanese men had a larger VAT and VSR in each stratum, despite substantially less
      obesity overall. In multiethnic studies, difference in abdominal fat distribution
      should be considered in exploring factors related to obesity.

PMID- 16446746
TI  - Body mass index, physical activity, and risk of renal cell carcinoma.
AB  - OBJECTIVE: To investigate the association between obesity and risk of renal cell
      carcinoma and to examine whether the association is modified by physical
      activity. SUBJECTS: A population-based case-control study of 406 patients with
      renal cell carcinoma and 2434 controls conducted in Iowa. METHODS: Information
      was collected on weight at the ages 20-29, 40-49, and 60-69 years, height,
      nonoccupational physical activity, diet, and other lifestyle factors. Renal cell
      carcinoma risk was estimated by odds ratios (ORs) and 95% confidence intervals
      (CIs), adjusting for age, total energy intake, and other confounding factors.
      RESULTS: Height and total energy intake were not associated with risk in either
      sex. In men, neither physical activity nor level of obesity in any period of life
      was significantly associated with risk. In women, lower physical activity was
      associated with higher risk (OR=2.5; 95% CI=1.2-5.2 comparing exercise <1
      time/month to >1 time/day). Compared with women in the lowest quartile for BMI,
      the risks of renal cell carcinoma for women in the highest 10% of BMI in their
      20s, 40s, and 60s were 1.4 (CI=0.6-3.1), 1.9 (CI=0.9-4.2), and 2.3 (CI=0.9-6.0),
      respectively. When analyses were limited to self-respondent data, the
      corresponding ORs were 2.9 (CI=1.2-7.4), 3.2 (CI=1.3-7.5), and 2.1 (CI=0.7-6.4),
      respectively. There was little evidence that physical activity modifies the
      association of BMI with renal cell carcinoma. CONCLUSION: Nonoccupational
      physical activity was inversely associated and obesity was positively associated
      with risk of renal cell carcinoma among women. The risk appeared to be greater
      for women in the highest 10% of BMI in their 40s. Our finding of little evidence
      of an interaction between physical activity and BMI requires confirmation.

PMID- 16446747
TI  - Effect of polymorphisms in the PPARGC1A gene on body fat in Asian Indians.
AB  - OBJECTIVE: To evaluate whether polymorphisms in the peroxisome proliferator
      activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene were related to body
      fat in Asian Indians. METHODS: Three polymorphisms of PPARGC1A gene, the
      Thr394Thr, Gly482Ser and +A2962G, were genotyped on 82 type 2 diabetic and 82
      normal glucose tolerant (NGT) subjects randomly chosen from the Chennai Urban
      Rural Epidemiology Study using PCR-RFLP, and the nature of the variants were
      confirmed using direct sequencing. Linkage disequilibrium (LD) was estimated from
      the estimates of haplotypic frequencies using an expectation-maximization
      algorithm. Visceral, subcutaneous and total abdominal fat were measured using
      computed tomography, whereas dual X-ray absorptiometry was used to measure
      central abdominal and total body fat. RESULTS: None of the three polymorphisms
      studied were in LD. The genotype (0.59 vs 0.32, P=0.001) and allele (0.30 vs
      0.17, P=0.007) frequencies of Thr394Thr polymorphism were significantly higher in
      type 2 diabetic subjects compared to those in NGT subjects. The odds ratio for
      diabetes (adjusted for age, sex and body mass index) for the susceptible
      genotype, XA (GA+AA) of Thr394Thr polymorphism, was 2.53 (95% confidence
      intervals: 1.30-5.04, P=0.009). Visceral and subcutaneous fat were significantly
      higher in NGT subjects with XA genotype of the Thr394Thr polymorphism compared to
      those with GG genotype (visceral fat: XA 148.2+/-46.9 vs GG 106.5+/-51.9 cm(2),
      P=0.001; subcutaneous fat: XA 271.8+/-167.1 vs GG 181.5+/-78.5 cm(2), P=0.001).
      Abdominal (XA 4521.9+/-1749.6 vs GG 3445.2+/-1443.4 g, P=0.004), central
      abdominal (XA 1689.0+/-524.0 vs GG 1228.5+/-438.7 g, P<0.0001) and non-abdominal
      fat (XA 18763.8+/-8789.4 vs GG 13160.4+/-4255.3 g, P<0.0001) were also
      significantly higher in the NGT subjects with XA genotype compared to those with
      GG genotype. The Gly482Ser and +A2962G polymorphisms were not associated with any
      of the body fat measures. CONCLUSION: Among Asian Indians, the Thr394Thr (G -->
      A) polymorphism is associated with increased total, visceral and subcutaneous
      body fat.

PMID- 16446748
TI  - Monitoring weight daily blocks the freshman weight gain: a model for combating
      the epidemic of obesity.
AB  - BACKGROUND: The Tissue Monitoring System (TMS) is an algorithm that estimates
      changes in body tissue from a series of daily weight measures. It is intended to
      provide people with a feedback of changes in their tissue weight so they may have
      a basis for estimating how much they would have to change their intake or
      expenditure to maintain their weight at a prescribed level. We tested the
      effectiveness of the TMS to prevent freshmen from gaining weight during their
      first semester in college. METHODS: In two similar but independent studies (Fall
      2002, 2003), female freshmen college students were given analog bathroom scales
      and instructed to weigh themselves each morning immediately after rising from
      bed, then e-mail their weight to our staff. After 7 days, a linear function was
      performed on the most recent 7 days of the weight-day function for each
      participant. In the first study, the slope of this function was e-mailed back to
      the participants. In the second study, the difference between last point and the
      original weight was determined, using linear regression techniques, converted to
      calories, and the information was e-mailed back to the participants. Control
      participants in both studies were weighed at the beginning and the end of the
      semester. RESULTS: The untreated controls gained 3.1+/-0.51 kg and 2.0+/-0.65 kg,
      respectively (P<0.01 for both studies), whereas weight gain of the experimental
      groups was 0.1+/-0.99 kg and -0.82+/-0.56 kg, values that were not significantly
      different than zero. CONCLUSIONS: The TMS appears to be an effective technique to
      help female college freshmen resist gaining weight in an environment that is
      conducive to weight gain. These results suggest that the TMS may be a useful
      method to help curb the slow increase in the prevalence of overweight and obesity
      that is characteristic of all industrialized societies.

PMID- 16446750
TI  - Relationship between preclinical abnormalities of global and regional left
      ventricular function and insulin resistance in severe obesity: a Color Doppler
      Imaging Study.
AB  - BACKGROUND: The aim of this study was to evaluate the relationship between
      insulin resistance and preclinical abnormalities of the left ventricular
      structure and function detected in severe obesity by Color Doppler Myocardial
      Imaging (CDMI). Forty-eight consecutive severely obese patients (Group O) (11
      males, 37 females, mean age 32.8+/-7 years) were enrolled. Forty-eight sex- and
      age-matched non-obese healthy subjects were also recruited as controls (Group C).
      All subjects underwent conventional 2D-Color Doppler echocardiography and CDMI.
      The homeostasis model assessment insulin resistance index (HOMA-IR) was used to
      assess insulin resistance results. Obese subjects had a greater left ventricular
      mass index (by height) (58.8+/-14 g/m(2.7)) than controls (37+/-8 g/m(2.7))
      (P<0.0001), owing to compensation response to volume overload caused by a greater
      cardiac output (P<0.02). Preload reserve was increased in obese subjects, as
      demonstrated by a significant increase in left atrial dimension (P<0.0001). Obese
      patients had a slightly reduced LV diastolic function (transmitral E/A ratio:
      Group O, 1.1+/-0.8 vs Group C, 1.5 +/-0.5; P<0.002). Cardiac deformation assessed
      by regional myocardial systolic strain and strain rate (SR) values was
      significantly lower (abnormal) in obese patients than in controls, both at the
      septum and lateral wall level. These strain and SR abnormalities were
      significantly related to body mass index. In addition, the early phase of
      diastolic function, evaluated using SR, was compromised in obese patients
      (P<0.001). The HOMA-IR values in obese patients were significantly higher (3.09+/
      1.6) than those determined in the control group (0.92+/-0.5) (P<0.0001). The HOMA
      IR values, in the obese group, were significantly related to systolic strain and
      SR values sampled at the septum level (P<0.0001). CONCLUSION: In conclusion, this
      study has demonstrated that obese patients pointed out systolic structural and
      functional abnormalities at a preclinical stage, in particular through strain and
      SR analysis; on the other hand, those altered CDMI parameters well distinguish
      obese subjects as compared with the control group. Furthermore, another main
      finding of the study was that myocardial deformation (systolic strain) could have
      a correlation with insulin resistance level.

PMID- 16446749
TI  - Relationship between fat cell size and number and fatty acid composition in
      adipose tissue from different fat depots in overweight/obese humans.
AB  - OBJECTIVE: To evaluate the body fat distribution and fat cell size and number in
      an overweight/obese population from both genders, and to determine the possible
      relationship between fat cell data from three different adipose tissue
      localizations (subcutaneous (SA), perivisceral and omental) and adipose tissue
      composition and dietary fatty acid. DESIGN: The sample consisted of 84
      overweight/obese patients (29 men and 55 women) who have undergone abdominal
      surgery. The adipocyte size and total fat cell number was studied. Fat cell data
      were related with anthropometric, adipose tissue and subject's habitual diet
      fatty acid composition. MEASUREMENTS: Fat cell size was measured according to a
      Sjostrom method from the three adipose depots. Total fat cell number was also
      calculated. The fatty acid composition of adipose tissue was examined by gas
      chromatography. The subjects diet was studied by a 7 days dietary record.
      RESULTS: Our data showed a negative relationship between the adipocyte size and
      the n-6 and n-3 fatty acids content of the SA adipose tissue (r=-0.286, P=0,040;
      r=-0.300, P=0.030) respectively, and the n-6 in the omental depots (r=-0.407,
      P=0.049) in the total population. Positive associations with the total of
      saturated (r=0.357, P=0.045) and negative (r=-0.544, P=0.001) with the n-9 fatty
      acids were observed when the relationship between the adipocyte number and the
      fatty acid composition of the different anatomical fat regions was studied.
      Dietary fatty acids composition positively correlated with fat cell size for the
      myristic acid (14:0) in men in the visceral depot (r=0.822, P=0.023), and for the
      saturated fatty acids (SFAs) in women in the omental depot (r=0.486, P=0.035).
      CONCLUSION: In the present study, for the first time in humans we found that n-3
      and n-6 fatty acids are related to a reduced adipocyte size according to the
      depot localization. In contrast, adipose tissue and dietary SFAs significantly
      correlated with an increase in fat cell size and number. No significant
      associations were found between n-9 acids content and adipocyte size. However, n
      9 adipose tissue fatty acids content was inversely associated with fat cell
      number showing that this type of fatty acid could limit hyperplasia in obese
      populations. The differences observed in the three different regions,
      perivisceral, omental and SA fat, indicate that this population adipose tissue
      have depot-specific differences.

PMID- 16446751
TI  - Pharmacogenetic research and data protection--challenges and solutions.

PMID- 16446754
TI  - Novel cardiovascular biomarkers and implications for clinical trials.

PMID- 16446753
TI  - Long-term urological outcomes in paediatric spinal cord injury.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: This retrospective review observes
      the evolution of bladder management by time and reports adult urological outcomes
      and complications in paediatric onset spinal cord injury (SCI). SETTING: Spinal
      Injuries Unit RNOH Stanmore. METHOD: In total, 10 traumatic SCI patients with
      mean age at injury of 13.6 years underwent treatment, for a mean period of 13.1
      years. Characteristics of injury were noted. Two diagnostic subgroups, neurogenic
      detrusor overactivity (NDO), and acontractile detrusor were made. Complications,
      treatment changes, operative procedures with follow-up were noted. RESULTS: In
      group 1 (6/10 patients) with NDO, five had DSD. Initial bladder management was
      reflex/urge voiding (n=4), suprapubic catheterisation (SPC), (n=1) and self
      intermittent catheterisation (SIC), (n=1). Two patients had multiple upper tract
      complications with decreased renal function, two recurrent symptomatic urinary
      infections and one; bladder calculus. In total, 12 operative procedures were
      performed to treat complications and change bladder management to, SIC+oxybutynin
      (n=3), ileal conduit (n=1), sacral anterior root stimulator implant (SARSI),
      (n=1), voiding on urge (n=1). In group 2 (4/10 patients) with a-contractile
      detrusor two had low compliance. Initial bladder management was SIC (n=3) and
      voiding on urge/straining (n=1). Two patients converted from SIC to permanent
      catheter drainage and reported complications. Incidental kidney stone was
      diagnosed in one. A total of four interventions were carried out with final
      management of SIC (n=2), voiding on urge/straining (n=1) and
      Mitrofanoff+ileocystoplasty (n=1). CONCLUSION: Bladder management in paediatric
      SCI is dependent on neurological level and type of injury; it changes with growth
      and is affected by changes in bladder management.

PMID- 16446752
TI  - Efficacy of rosiglitazone in a genetically defined population with mild-to
      moderate Alzheimer's disease.
AB  - Mild-to-moderate AD patients were randomized to placebo or rosiglitazone (RSG) 2,
      4 or 8 mg. Primary end points at Week 24 were mean change from baseline in AD
      Assessment Scale-Cognitive (ADAS-Cog) and Clinician's Interview-Based Impression
      of Change Plus Caregiver Input global scores in the intention-to-treat population
      (N=511), and results were also stratified by apolipoprotein E (APOE) genotype
      (n=323). No statistically significant differences on primary end points were
      detected between placebo and any RSG dose. There was a significant interaction
      between APOE epsilon4 allele status and ADAS-Cog (P=0.014). Exploratory analyses
      demonstrated significant improvement in ADAS-Cog in APOE epsilon4-negative
      patients on 8 mg RSG (P=0.024; not corrected for multiplicity). APOE epsilon4
      positive patients did not show improvement and showed a decline at the lowest RSG
      dose (P=0.012; not corrected for multiplicity). Exploratory analyses suggested
      that APOE epsilon4 non-carriers exhibited cognitive and functional improvement in
      response to RSG, whereas APOE epsilon4 allele carriers showed no improvement and
      some decline was noted. These preliminary findings require confirmation in
      appropriate clinical studies.

PMID- 16446755
TI  - Genetic association studies: personalized medicine in cardiac transplantation.

PMID- 16446769
TI  - CIBIS III: what is the optimum order for initiating chronic heart failure medical
      therapy?

PMID- 16446770
TI  - Can manual thrombus aspiration improve myocardial reperfusion?

PMID- 16446771
TI  - What are the long-term outcomes of using FFR findings to determine treatment
      strategy?

PMID- 16446772
TI  - What is the optimum role and timing of early invasive management of patients with
      acute coronary syndromes?

PMID- 16446773
TI  - Does rosuvastatin improve lipid levels in patients with the metabolic syndrome
      more effectively than atorvastatin?

PMID- 16446774
TI  - Can the transfer function method of assessing baroreflex sensitivity predict
      outcome in heart failure patients?

PMID- 16446775
TI  - Can colchicine prevent recurrence of new-onset acute pericarditis?

PMID- 16446776
TI  - The hematopoietic system: a new niche for the renin-angiotensin system.
AB  - The role of the renin-angiotensin system was previously thought to be restricted
      to the cardiovascular system. It now appears that this system also has important
      functions in other tissues. Hematopoiesis can be affected by inhibitors of the
      renin system in patients and in various experimental models. The renin system,
      particularly angiotensin II, has a role in different stages of hematopoiesis,
      notably during the first wave in the chick embryo (primitive hematopoiesis) and
      in the human adult (definitive hematopoiesis). In addition, the renin-angiotensin
      system in mice is involved in reconstitutive hematopoiesis following experimental
      irradiation; inhibition of this system improved the hematopoietic recovery in
      this situation. The clinical relevance and therapeutic applications of these
      findings offer a new area of clinical research. In this article, we review the
      evidence for a role for the renin system in the control of hematopoiesis at its
      different stages.

PMID- 16446777
TI  - Impact of implantable-cardioverter-defibrillator trials on clinical management of
      patients with heart failure.
AB  - Heart failure is a deadly disease. Every year, tens of thousands of patients die
      from this condition, many of them suddenly. Efforts aimed at reducing mortality
      centered initially on antagonizing the neurohormonal system, which is
      maladaptively upregulated in response to myocardial failure. Antagonists of the
      renin-angiotensin-aldosterone and adrenergic nervous systems have reduced the
      rates of cardiovascular mortality and sudden cardiac death. Antiarrhythmic drug
      therapy has not fared as well. Consequently, efforts to reduce the risk of sudden
      death have focused on the use of implantable cardioverter-defibrillators (ICDs).
      How best to identify patients who will benefit from this invasive and expensive
      therapy has yet to be clearly determined. In this review, we discuss the
      effectiveness of ICDs in primary and secondary prevention of sudden death in
      heart failure patients, and examine the impact that the use of ICDs has had on
      clinical decision making.

PMID- 16446779
TI  - Therapy insight: how changes in renal function with increasing age affect
      cardiovascular drug prescribing.
AB  - Age is well recognized as a powerful prognostic factor in the setting of
      cardiovascular disease. With the aging of the US population, it is projected that
      more than 50 million people will be aged over 65 years by the year 2020. This
      growing elderly population has increased rates of morbidity and mortality owing
      to cardiovascular disease; however, proven therapies for prevention and treatment
      are often underused in older patients, largely because physicians perceive them
      as being frail and have limited understanding of age-related unique adverse and
      therapeutic effects. Advancing age is associated with a number of physiologic and
      pathophysiologic changes that impact the toxic effects, efficacy and dosing of
      many medications. Decreases in lean muscle mass affect the volume of
      distribution, and reductions in hepatic function affect the metabolism of many
      medications. Age-related reductions in renal function might have the most
      profound impact on the safety profile and dosing of medications in elderly
      patients. The strong association between renal and cardiovascular disease makes
      recognition of renal dysfunction and appropriate dose adjustment particularly
      important in elderly patients with cardiovascular disease. This article reviews
      current approaches to the estimation of renal function, and unique considerations
      related to prescribing medication for elderly patients with concomitant renal and
      cardiovascular disease.

PMID- 16446778
TI  - The impact of progenitor cells in atherosclerosis.
AB  - During the pathogenesis of arteriosclerosis, endothelial cells on the arterial
      wall damaged by various means were initially thought to be replaced by
      replication of neighboring cells. Smooth-muscle cells (SMCs) were also thought to
      migrate from the media into the intima, where they constituted arteriosclerotic
      lesions. This concept has been challenged, however, by the discovery that
      progenitor cells in the circulation and adventitia contribute to endothelial
      repair and SMC accumulation. Studies have demonstrated that atherosclerosis is a
      pathophysiologic process initiated by endothelial death in specific areas, such
      as bifurcation regions, and with subsequent replacement by endothelial progenitor
      cells. Differentiation of the neoendothelial cells into mature endothelium takes
      several days or weeks, during which LDL deposits in the intima. Blood mononuclear
      cells also adhere to neoendothelial cells and migrate into the subendothelial
      space. Meanwhile, progenitor cells from blood and the adventitia migrate into the
      intima, where they proliferate and differentiate into neo-SMCs. All risk factors
      for atherosclerosis can exert their effects on the vessel wall partly via
      increase in endothelial turnover, inhibition of progenitor-cell differentiation,
      and promotion of smooth-muscle and macrophage accumulation in lesions. Thus,
      progenitor cells comprise the main cell source responsible for the formation of
      atherosclerotic lesions, which appear in the context of inflammatory disease.
      Here I provide an update on research and discuss the role of progenitor cells in
      the pathogenesis of atherosclerosis.

PMID- 16446780
TI  - Implantation of a cardioverter-defibrillator in a patient with cardiac
      amyloidosis.
AB  - BACKGROUND: A 49-year-old woman presented with chest pain of 10 days' duration.
      Initial physical examinations and laboratory investigations were normal. The
      patient received symptomatic treatment with beta-blockers, which continued
      following normal findings on coronary angiogram. About 7 months later the patient
      developed ventricular arrhythmias, with clinical evidence of left ventricular
      heart failure. Her arrhythmia symptoms persisted despite pharmacological therapy
      with atenolol, carvedilol and amiodarone. INVESTIGATIONS: Physical examination,
      electrocardiography, laboratory testing, serologic testing, exercise-tolerance
      testing, coronary angiography, chest radiography, cardiac MRI, tongue biopsy,
      bone-marrow biopsy, CT scan, iodine-123-labeled serum-amyloid-P-component
      scintigraphy. DIAGNOSIS: Systemic primary amyloidosis (AL amyloidosis), with
      predominant cardiac involvement. MANAGEMENT: Pharmacological antiarrhythmic
      therapy and cardioverter-defibrillator implantation. Chemotherapy was planned
      but, despite intervention, the patient died before this treatment could begin.

PMID- 16446781
TI  - Rapid and simple comparison of messenger RNA levels using real-time PCR.
AB  - Real-time polymerase chain reaction (PCR) constitutes a significant improvement
      over traditional end-point PCR, as it allows the quantification of starting
      amounts of nucleic acid templates, in real-time. However, quantification requires
      validation through numerous internal controls and standard curves. We describe in
      this paper a simple protocol which uses real-time PCR to compare mRNA levels of a
      gene of interest between different experimental conditions. Comparative real-time
      PCR can be a relatively low-cost method and does not require sequence-specific
      fluorescent reporters. Moreover, several genes from a set of experiments can be
      assessed in a single run. Thus, in addition to providing a comparative profile
      for the expression of a gene of interest, this method can also provide
      information regarding the relative abundance of different mRNA species.

PMID- 16446782
TI  - Listeria monocytogenes invades the epithelial junctions at sites of cell
      extrusion.
AB  - Listeria monocytogenes causes invasive disease by crossing the intestinal
      epithelial barrier. This process depends on the interaction between the bacterial
      surface protein Internalin A and the host protein E-cadherin, located below the
      epithelial tight junctions at the lateral cell-to-cell contacts. We used
      polarized MDCK cells as a model epithelium to determine how L. monocytogenes
      breaches the tight junctions to gain access to this basolateral receptor protein.
      We determined that L. monocytogenes does not actively disrupt the tight
      junctions, but finds E-cadherin at a morphologically distinct subset of
      intercellular junctions. We identified these sites as naturally occurring regions
      where single senescent cells are expelled and detached from the epithelium by
      extrusion. The surrounding cells reorganize to form a multicellular junction that
      maintains epithelial continuity. We found that E-cadherin is transiently exposed
      to the lumenal surface at multicellular junctions during and after cell
      extrusion, and that L. monocytogenes takes advantage of junctional remodeling to
      adhere to and subsequently invade the epithelium. In intact epithelial
      monolayers, an anti-E-cadherin antibody specifically decorates multicellular
      junctions and blocks L. monocytogenes adhesion. Furthermore, an L. monocytogenes
      mutant in the Internalin A gene is completely deficient in attachment to the
      epithelial apical surface and is unable to invade. We hypothesized that L.
      monocytogenes utilizes analogous extrusion sites for epithelial invasion in vivo.
      By infecting rabbit ileal loops, we found that the junctions at the cell
      extrusion zone of villus tips are the specific target for L. monocytogenes
      adhesion and invasion. Thus, L. monocytogenes exploits the dynamic nature of
      epithelial renewal and junctional remodeling to breach the intestinal barrier.

PMID- 16446783
TI  - Genome-wide analysis of group a streptococci reveals a mutation that modulates
      global phenotype and disease specificity.
AB  - Many human pathogens produce phenotypic variants as a means to circumvent the
      host immune system and enhance survival and, as a potential consequence, exhibit
      increased virulence. For example, it has been known for almost 90 y that clinical
      isolates of the human bacterial pathogen group A streptococci (GAS) have
      extensive phenotypic heterogeneity linked to variation in virulence. However, the
      complete underlying molecular mechanism(s) have not been defined. Expression
      microarray analysis of nine clinical isolates identified two fundamentally
      different transcriptomes, designated pharyngeal transcriptome profile (PTP) and
      invasive transcriptome profile (ITP). PTP and ITP GAS differed in approximately
      10% of the transcriptome, including at least 23 proven or putative virulence
      factor genes. ITP organisms were recovered from skin lesions of mice infected
      subcutaneously with PTP GAS and were significantly more able to survive
      phagocytosis and killing by human polymorphonuclear leukocytes. Complete genome
      resequencing of a mouse-derived ITP GAS revealed that the organism differed from
      its precursor by only a 7-bp frameshift mutation in the gene (covS) encoding the
      sensor kinase component of a two-component signal transduction system implicated
      in virulence. Genetic complementation, and sequence analysis of covR/S in 42 GAS
      isolates confirmed the central role of covR/S in transcriptome, exoproteome, and
      virulence modulation. Genome-wide analysis provides a heretofore unattained
      understanding of phenotypic variation and disease specificity in microbial
      pathogens, resulting in new avenues for vaccine and therapeutics research.

PMID- 16446785
TI  - Signal processing in the TGF-beta superfamily ligand-receptor network.
AB  - The TGF-beta pathway plays a central role in tissue homeostasis and
      morphogenesis. It transduces a variety of extracellular signals into
      intracellular transcriptional responses that control a plethora of cellular
      processes, including cell growth, apoptosis, and differentiation. We use
      computational modeling to show that coupling of signaling with receptor
      trafficking results in a highly versatile signal-processing unit, able to sense
      by itself absolute levels of ligand, temporal changes in ligand concentration,
      and ratios of multiple ligands. This coupling controls whether the response of
      the receptor module is transient or permanent and whether or not different
      signaling channels behave independently of each other. Our computational approach
      unifies seemingly disparate experimental observations and suggests specific
      changes in receptor trafficking patterns that can lead to phenotypes that favor
      tumor progression.

PMID- 16446786
TI  - [Helicobacter pylori infection: Nobel Prize in Medicine].

PMID- 16446784
TI  - Computational analysis and prediction of the binding motif and protein
      interacting partners of the Abl SH3 domain.
AB  - Protein-protein interactions, particularly weak and transient ones, are often
      mediated by peptide recognition domains, such as Src Homology 2 and 3 (SH2 and
      SH3) domains, which bind to specific sequence and structural motifs. It is
      important but challenging to determine the binding specificity of these domains
      accurately and to predict their physiological interacting partners. In this
      study, the interactions between 35 peptide ligands (15 binders and 20 non
      binders) and the Abl SH3 domain were analyzed using molecular dynamics simulation
      and the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. The calculated
      binding free energies correlated well with the rank order of the binding peptides
      and clearly distinguished binders from non-binders. Free energy component
      analysis revealed that the van der Waals interactions dictate the binding
      strength of peptides, whereas the binding specificity is determined by the
      electrostatic interaction and the polar contribution of desolvation. The binding
      motif of the Abl SH3 domain was then determined by a virtual mutagenesis method,
      which mutates the residue at each position of the template peptide relative to
      all other 19 amino acids and calculates the binding free energy difference
      between the template and the mutated peptides using the Molecular
      Mechanics/Poisson-Boltzmann Solvent Area method. A single position mutation free
      energy profile was thus established and used as a scoring matrix to search
      peptides recognized by the Abl SH3 domain in the human genome. Our approach
      successfully picked ten out of 13 experimentally determined binding partners of
      the Abl SH3 domain among the top 600 candidates from the 218,540 decapeptides
      with the PXXP motif in the SWISS-PROT database. We expect that this physical
      principle based method can be applied to other protein domains as well.

PMID- 16446787
TI  - [Mechanisms of human pathogenicity and adaptability of avian influenza A (H5N1)
      strains].

PMID- 16446788
TI  - [Antifungal inhibitors of glucan synthesis].

PMID- 16446789
TI  - [Dispensation and cost of antimicrobials in Spain (1998-2000)].
AB  - The aim of this study was to analyze the dispensation of anti-infectives for
      systemic use, excluding immune sera and immunoglobulins and vaccines, made in all
      of Spain's pharmaceutical offices in a two-year period and to analyze their
      pharmacological cost. A retrospective pharmacoepidemiological study was made of
      dispensations in Spain's pharmaceutical offices for medicines belonging to the
      J01, J02, J04 and J05 subgroups. The dispensations were quantified as defined
      daily doses per 1,000 inhabitants per day (DID). The economic cost of the
      dispensing was expressed in absolute terms and as CID (cost per 1,000 inhabitants
      per day). The total DID of anti-infective drugs was 32.11 (30.70 for
      antibacterials, 0.53 antimycotics, 0.73 for antimicrobacterials and 0.16 for
      antivirals). In the J01 subgroup the most frequently used were penicillins,
      macrolides, cephalosporins and quinolones. And the most frequently used drugs
      were amoxicillin, amoxicillin and clavulanic acid, clarithromycin, cefuroxime
      axetil and ciprofloxacin. The total cost was 1,403,462,770 euros, and the CID was
      47.18 euros.

PMID- 16446791
TI  - [In vitro activity of furazolidone and nitrofurantoin in Helicobacter pylori
      clinical isolates and study of mutation rate].
AB  - Clarithromycin, amoxicillin, tetracycline and metronidazole are the most
      frequently used antimicrobials for Helicobacter pylori infection treatment. While
      tetracycline and amoxicillin resistance are rare, clarithromycin and
      metronidazole resistance vary in different populations and are considered factors
      for treatment failure. The aim of this study was to determine the in vitro
      activity of furazolidone and nitrofurantoin in 164 H. pylori clinical isolates by
      agar dilution and to determine the spontaneous mutation rate. Metronidazole and
      clarithromycin resistance were 23.77% (CI95%: 18.96-29.14) and 16.78% (CI95%:
      12.64-21.62), respectively; moreover, 1.4% (CI95%: 0.38-3.54) were intermediate
      to clarithromycin. All the isolates were susceptible to amoxicillin and
      tetracycline. Furazolidone and nitrofurantoin resistance rates were 1.82% (CI95%:
      0.37-5.25) and 0.6% (CI95%: 0-3.35), respectively. The three furazolidone
      resistant strains were nitrofurantoine-susceptible (MIC 4 mg/l for furazolidone
      and 2 mg/l for nitrofurantoin) and the nitrofurantoin-resistant strains were
      furazolidone-susceptible (MIC 4 mg/l for nitrofurantoin and 1 mg/l for
      furazolidone). These four strains were metronidazole-resistant (MIC 16 mg/l).
      Furazolidone or nitrofurantoin spontaneous mutants were not detected in the eight
      H. pylori strains tested. However, mutants with resistance to metronidazole were
      found with all the strains with a mutation rate of 7.4 x 10(-10) to 9.4 x 10(
      10). Furazolidone and nitrofurantoin showed an excellent in vitro activity
      against the H. pylori clinical isolates included herein, supporting the
      usefulness of furazolidone as second-line antimicrobial after treatment failure
      or as first-line therapy in populations with low economical resources.

PMID- 16446790
TI  - [Activity of voriconazole against yeasts isolated from blood culture determined
      by two methods].
AB  - The in vitro activity of voriconazole has been determined by two methods: the
      reference M27-A2 and the marketed Sensititre YeastOne microdilution colorimetric
      method. The agreement (+/-2 dilutions) and correlation between methods as well as
      the percentage of errors has been determined. A total of 144 yeasts (47 Candida
      albicans, 52 C. parapsilosis, 13 C. tropicalis, 10 C. krusei, 9 C. glabrata, 2 C.
      guilliermondii, 1 C. colliculosa, 1 C. dubliniensis, 2 Trichosporum asahii, 1 T.
      mucoide, 1 Trichosporum spp., 1 Kloakera apis, 2 Pichia ohmeri, and 2 Rhodotorula
      glutinis) isolated from blood culture between October 2002 and May 2005 were
      assayed. Voriconazole has shown good in vitro activity. The rate of voriconazole
      susceptible (MIC < or =1 mg/l) strains was 97% and the MIC90 0.25 mg/l by the two
      methods. The overall percentage of agreement between methods was 86% (range 44.23
      100%) and the Pearson's coefficient of correlation was 0.961. Categorical
      agreement was strain dependent and ranged from 84.6% for emergent yeasts to 100%
      for the other species tested except for C. glabrata (66.6%). No major or very
      major errors were found, the percentage of minor errors being 1.38%. Only one C.
      tropicalis and one C. glabrata strain were resistant (MIC > or =4 mg/l) to
      voriconazole (1.38%) by the reference method. The colorimetric method identified
      the voriconazole-resistant C. tropicalis strain, and classified the C. glabrata
      as susceptible-dose dependent. The colorimetric method is a potential alternative
      method for testing the susceptibility of yeast in a clinical laboratory and
      identifies the susceptible strains (100% agreement) very well. Nevertheless,
      further studies including more voriconazole-resistant strains are required to
      determine the ability of the method to identify resistance, which is the goal of
      susceptibility tests.

PMID- 16446792
TI  - [Treatment of community-acquired urinary infections: current perspectives and
      patient clinical approach].

PMID- 16446793
TI  - [Evolution of methicillin resistance in Staphylococcus aureus in Cordoba (Spain)
      in the years 2002-2005].
AB  - In the last few years, methicillin-resistant Staphylococcus aureus (MRSA) has
      become a very important human pathogen. Our aim was to study the evolution of
      methicillin resistance of Staphylococcus aureus strains isolated in our hospital
      over a four-year period and to compare our situation with the rest of Spain and
      Europe. The rates varied from 39.9% in 2002 to 46.4% in 2005. Units with the
      highest rate were ICU and surgical wards. We found no glycopeptide-resistant
      strains.

PMID- 16446794
TI  - [Severe pelvic inflammatory disease. Response to ertapenem].
AB  - Pelvic inflammatory disease (PID) is an important health problem. Delay in
      diagnosis and effective treatment contributes to inflammatory sequelae with risk
      of future fertility problems and chronic pelvic pain. Treatment regimens must
      provide empiric, broad-spectrum coverage of likely pathogens but also take into
      account patient's risk profile. In this article we report the case of a young
      woman affected by a rare genital malformation who required the creation of a
      neovagina made of abdominal skin. Years later, the patient presented with
      symptoms that support the diagnosis of PID. There was no clinical analytical
      response to classical parenteral antimicrobial regimen, even after surgical
      intervention for tubal abscess. Peptostreptococci isolated in abdominal cavity
      culture showed an infrequent clindamycin resistance, so we started monotherapy
      treatment with ertapenem, with excellent results. In conclusion, more clinical
      trials are needed to discover the pathogens usually involved in PID in our
      setting and their antibiotic resistance to re-evaluate standard antimicrobial
      regimens and perhaps recommend new agents, such as ertapenem.

PMID- 16446795
TI  - [Antiinfectious therapy was born with a color: mauve].

PMID- 16446796
TI  - Bifunctional transition metal-based molecular catalysts for asymmetric syntheses.
AB  - The discovery and development of conceptually new chiral bifunctional transition
      metal-based catalysts for asymmetric reactions is described. The chiral
      bifunctional Ru catalyst was originally developed for asymmetric transfer
      hydrogenation of ketones and imines and is now successfully applicable to
      enantioselective C-C bond formation reaction with a wide scope and high
      practicability. The deprotonation of 1,3-dicarbonyl compounds with the chiral
      amido Ru complexes leading to the amine Ru complexes bearing C- or O-bonded
      enolates, followed by further reactions with electrophlies gives C-C bond
      formation products. The present bifunctional Ru catalyst offers a great
      opportunity to open up new fundamentals for stereoselective molecular
      transformation including enantioselective C-H and C-C as well as C-O, C-N bond
      formation.

PMID- 16446797
TI  - Concise synthesis of 22-hydroxyacuminatine, cytotoxic camptothecinoid from
      Camptotheca acuminata, by pyridone benzannulation.
AB  - A short, efficient synthesis of 22-hydroxyacuminatine, starting from a readily
      accessible hydroxy pyridone, is presented; key steps include a Heck coupling with
      methyl pentadienoate, a flash vacuum pyrolytic cyclization, and a Friedlander
      condensation.

PMID- 16446798
TI  - Rapid methylation on carbon frameworks useful for the synthesis of 11CH3
      incorporated PET tracers: Pd(0)-mediated rapid coupling of methyl iodide with an
      alkenyltributylstannane leading to a 1-methylalkene.
AB  - The Pd(0)-mediated rapid coupling of methyl iodide with an excess of
      alkenyltributylstannane was examined with the aim of incorporating a short-lived
      11C-labeled methyl group into a biologically significant organic compound with a
      1-methylalkene unit for the synthesis of a PET tracer. Four sets of reaction
      conditions (A-D) were used, all performed in DMF at 60 degrees C for 5 min.
      Condition B, using CH3I/stannane/Pd2(dba)3/P(o-tolyl)3/CuCl/K2CO3 (1:40:0.5:4
      6:2:5), works well in almost all cases. Condition D, using
      CH3I/stannane/Pd2(dba)3/P(o-tolyl)3/CuX (X = Br, Cl, or I)/CsF (1:40:0.5-5:2-20:2
      20:5-50), shows the best results with regard to general applicability to tin
      substrates, affording the corresponding methylated product in >90% yield based on
      consumption of methyl iodide. P(t-Bu)2Me was less effective than P(o-tolyl)3,
      particularly for alpha,beta-unsaturated carbonyl substrates. No regio- or
      stereoisomerization occurred under these reaction conditions. The efficiency of
      the protocol was demonstrated by synthesis of an 11C-methylated compound.

PMID- 16446799
TI  - Synthesis and biological evaluation of leucine enkephalin turn mimetics.
AB  - A cyclic Leu-enkephalin mimetic containing a 7-membered ring, and two linear
      analogues, has been prepared on solid phase. In the cyclic mimetic the
      intramolecular (1-4) hydrogen bond found in crystalline Leu-enkephalin has been
      replaced by an ethylene bridge. In addition, the amide bond between Tyr1 and Gly2
      has been replaced by a methylene ether isostere and Gly3 has been deleted. The
      two linear analogues both contain the methylene ether isostere instead of the
      Tyr1-Gly2 amide bond and the shorter of the two lacks Gly3. The three compounds,
      and a beta-turn mimetic analogous to the 7-membered turn mimetic but with Gly3
      included, were evaluated for specific binding to micro- and delta-opioid
      receptors in rat brain membranes. With the exception of the beta-turn mimetic the
      three other Leu-enkephalin analogues all bound with varying affinity to the micro
      and delta-opioid receptors. From the results it could be concluded that Leu
      enkephalin binds in a turn conformation to the opiate receptors, but that this
      conformation is not a (1-4) beta-turn.

PMID- 16446800
TI  - Conformational preference in aromatic amides bearing chiral ortho substituents:
      its origin and application to relayed stereocontrol.
AB  - Tertiary aromatic amides bearing stereogenic centres ortho to the amide group may
      adopt two diastereoisomeric conformations which interconvert slowly on the NMR
      timescale at ambient temperature, and are therefore detectable by NMR. Certain
      classes of stereogenic centre--particularly sulfoxides, ephedrine-derived
      oxazolidines, and proline-derived imidazolidines--strongly bias the population of
      the two conformers. We propose a model, supported by molecular mechanics
      calculations, which rationalises the sense and magnitude of the conformational
      selectivity attained in terms of the steric and electronic properties of the
      controlling centre. The control over conformation may be exploited either by
      trapping the favoured conformer as an atropisomer, or by using it to relay
      information about the stereochemistry of the controlling centre.

PMID- 16446802
TI  - Diastereoselective synthesis of atropisomers containing two non-biaryl
      stereogenic axes: stereochemical relay through stereogenic centres in
      dihydrostilbene-2,2'-dicarboxamides.
AB  - Addition of laterally lithiated tertiary aromatic amides to benzaldimines
      controls the formation of a new stereogenic centre adjacent to the benzaldimine
      aromatic ring. Drawing on the fact that such amino-substituted stereogenic
      centres may themselves control the conformation of amides, with amido-substituted
      benzaldimines we found it becomes possible to relay stereochemistry from one
      amide to another via this intervening stereogenic centre. A group of
      dihydrostilbene-2,2'-dicarboxamide derivatives bearing one or two stereogenic
      axes are made by this method, which demonstrates the use of combined kinetic and
      thermodynamic control for the relay of stereochemical information.

PMID- 16446801
TI  - Conformational arm-wrestling: battles for stereochemical control in benzamides
      bearing matched and mismatched chiral 2- and 6-substituents.
AB  - The orientation of a tertiary amide group adjacent to an aromatic ring may be
      governed by the stereochemistry of an adjacent chiral substituent. With a chiral
      substituent in both ortho positions, matched/mismatched pairs of isomers result.
      Evidence for matched stereochemistry is provided by the clean NMR spectra of
      single conformers, while mismatching gives poor or unexpected selectivities in
      the formation of chiral substituents, or mixtures of amide conformers. Attempts
      to use the match-mismatch effect to select for racemic pairs of enantiomeric
      substituents, and hence develop a "racemate-sequestering" reagent, are described,
      along with the use of "matching" to scavenge a single enantiomer of a diamine
      from material of incomplete enantiomeric purity.

PMID- 16446803
TI  - Binding of monovalent metal cations by the p-sulfonatocalix[4]arene: experimental
      evidence for cation-pi interactions in water.
AB  - Gibbs free energies, enthalpies and entropies for the binding of Na+, K+, Rb+,
      Cs+, Ag+, Tl+ and NH4+ by the p-sulfonatocalix[4]arene in water are determined by
      microcalorimetry. Whereas no significant heat effect is detected with Na+ or Ag+,
      suggesting that these cations are not complexed, weak but selective binding is
      observed with the other cations. The whole set of thermodynamic parameters, which
      demonstrate that the cations bind inside the cavity of the calixarene, evidence
      the importance of the cation-pi interactions for these complexes in water.

PMID- 16446804
TI  - Preparation of 2,3-dihydroselenolo[2,3-b]pyridines and related compounds by free
      radical means.
AB  - Photolysis of the thiohydroximate ester derivative 21 of 2-carboethoxy-2-(2
      (benzylseleno)pyridin-3-yl)tridecylcarboxylic acid (20) affords 2-dodecyl-2
      carboethoxy-2,3-dihydroselenolo[2,3-b]pyridine (22) in 89% yield in a process
      presumably involving intramolecular homolytic substitution by a tertiary alkyl
      radical at selenium with loss of a benzyl radical. Alternatively, rearrangement
      of O-(omega-haloalkyl)esters 34 of 2-carboethoxy-N-hydroxypyridine-2-selone
      affords azonianaphthalenium halides 37 in 79% yield.

PMID- 16446805
TI  - Atomic and bond topological properties of the tripeptide L-alanyl-L-alanyl-L
      alanine based on its experimental charge density obtained at 20 K.
AB  - A 20 K high resolution X-ray data set of L-Ala-L-Ala-L-Ala*1/2 H2O was measured
      using an ultra-low temperature laboratory setup, that combines area detection and
      a closed cycle helium cryostat. The charge density determination includes
      integration of atomic basins and topological analysis according to Bader's
      quantum theory of atoms in molecules. Two tripeptide units are found in the
      asymmetric unit, allowing the assessment of transferability of bond topological
      and atomic properties taking also into consideration previous data of
      oligopeptides. With respect to invariom modeling the limits of such
      transferability are investigated and the results of this study show the validity
      of the nearest/next-nearest neighbour approximation and support the use of
      database approaches for electron density modeling of macromolecules.

PMID- 16446807
TI  - Michael reactions carried out using a bench-top flow system.
AB  - The Michael reaction between methyl 1-oxoindan-2-carboxylate and methyl vinyl
      ketone was achieved successfully by pumping solutions of the reactants in toluene
      through a fluid bed of Amberlyst A21 at 50 degrees C. The use of a fluid bed
      reactor is attractive as it allows gel-type beads, i.e. the type of bead used in
      most studies of polymer-supported (PS) organic reactions, to be used
      satisfactorily in a flow system. When polymer-supported cinchonidine was used in
      place of Amberlyst A21, the Michael product was obtained in high yield with an
      enantiomeric excess (ee) of 51%. This % ee is comparable to that achieved when
      the reaction was catalysed by cinchonidine itself.

PMID- 16446806
TI  - Structure-based design of imidazole-containing peptidomimetic inhibitors of
      protein farnesyltransferase.
AB  - A series of imidazole-containing peptidomimetic PFTase inhibitors and their co
      crystal structures bound to PFTase and FPP are reported. The structures reveal
      that the peptidomimetics adopt a similar conformation to that of the extended
      CVIM tetrapeptide, with the imidazole group coordinating to the catalytic zinc
      ion. Both mono- and bis-imidazole-containing derivatives, 13 and 16, showed
      remarkably high enzyme inhibition activity against PFTase in vitro with IC50
      values of 0.86 and 1.7 nM, respectively. The peptidomimetics were also highly
      selective for PFTase over PGGTase-I both in vitro and in intact cells. In
      addition, peptidomimetics and were found to suppress tumor growth in nude mouse
      xenograft models with no gross toxicity at a daily dose of 25 mg kg(-1).

PMID- 16446808
TI  - Practical formal total synthesis of (rac)- and (S)-camptothecin.
AB  - A practical, efficient and scalable formal total synthesis of (rac)- and (S)
      camptothecin is described, which proceeds via the known DE ring building blocks
      19 and (S)-19, respectively. The racemic synthesis starts from diethyl oxalate
      and uses straightforward carbonyl chemistry in order to generate the pyridone
      ring system. 19 was formed in 8.4% overall yield over 9 linear steps avoiding any
      chromatographic purification. The asymmetric version of this approach encompassed
      a diastereoselective Grignard addition to the enantiomerically pure alpha
      ketoester 30 in order to generate the (S)-configured quaternary stereocenter. The
      auxiliary could be recycled in high yield and was successfully reused multiple
      times. The final steps paralleled the racemic approach. (S)-19 was thus prepared
      in 9.4% overall yield (er = 95 : 5) over 10 steps.

PMID- 16446809
TI  - Practical synthesis of potential endothelin receptor antagonists of 1,4
      benzodiazepine-2,5-dione derivatives bearing substituents at the C3-, N1- and N4
      positions.
AB  - The expedient synthesis of various 1,4-benzodiazepine-2,5-dione compounds,
      particularly those having substituents at the C3-, N1- and N4-positions is
      achieved. The important features in these synthetic strategies include: (i) using
      the coupling reaction of isatoic anhydride with alpha-amino ester for direct
      construction of the core structure of 1,4-benzodiazepine-2,5-dione; (ii) using
      potassium carbonate as the base of choice for selective alkylation at the N1
      site, while using lithiated 2-ethylacetanilide as the required base to furnish
      the N4-alkylation; and (iii) using 2-nitrobenzoyl chloride as a synthetic
      equivalent of anthranilic acid to facilitate the polyethylene resin-bound liquid
      phase combinatorial synthesis. The prepared 1,4-benzodiazepine-2,5-dione
      compounds are evaluated for endothelin receptor antagonism by a functional assay
      that measures the inhibitory activity against the change of intramolecular
      calcium ion concentration induced by endothelin-1. The preliminary results
      indicate that 1,4-benzodiazepine-2,5-diones bearing two flanked aryl substituents
      at the N1- and N4-sites show better inhibitory activity than the corresponding
      unalkylated and N-monoalkylated compounds. A promising candidate, 1-benzyl-7
      chloro-3-isopropyl-4-(3-methoxybenzyl)-1,4-benzodiazepine-2,5-dione (17b),
      exhibits an IC50 value in low nM range.

PMID- 16446810
TI  - Control of self-aggregation of fullerenes by connection with calix[4]arene:
      solvent- and guest-effects to particle size.
AB  - A new molecular design of fullerene derivatives exhibiting trigger-responsive
      self-aggregation in organic solvents has been established. Calix[4]arene was
      covalently connected with fullerene in order to apply host-guest interaction to
      the aggregation control. The self-assembly behaviour was studied in organic
      solvents by UV-vis absorption spectroscopy, dynamic light scattering and
      transmission electron microscopy. Results show that the bisfullerene formed self
      aggregations with a low polydispersity index due to the fullerenes' tendency to
      aggregate in polar organic solvents. Furthermore, the aggregate sizes can be
      changed readily by solvent composition and the addition of guest cations.
      Especially, disaggregation of the bisfullerene was induced by addition of LiClO4
      or NaClO4.

PMID- 16446811
TI  - An expeditious stereoselective synthesis of natural (-)-Cassine via cascade HWE
      [3 + 2]-cycloaddition process.
AB  - l-Rhamnose is transformed to (-)-Cassine via a remarkable four step one pot
      reaction. The Horner-Wadsworth-Emmons [3 + 2]-1,3-dipolar cycloaddition reaction
      cascade is the pivotal step in this reaction sequence and makes the synthesis
      highly efficient.

PMID- 16446812
TI  - Mechanistic insights into triterpene synthesis from quantum mechanical
      calculations. Detection of systematic errors in B3LYP cyclization energies.
AB  - Most quantum mechanical studies of triterpene synthesis have been done on small
      models. We calculated mPW1PW91/6-311+G(2d,p)//B3LYP/6-31G* energies for many
      C30H51O+ intermediates to establish the first comprehensive energy profiles for
      the cationic cyclization of oxidosqualene to lanosterol, lupeol, and hopen-3beta
      ol. Differences among these 3 profiles were attributed to ring strain, steric
      effects, and proton affinity. Modest activation energy barriers and the ample
      exothermicity of most annulations indicated that the cationic intermediates
      rarely need enzymatic stabilization. The course of reaction is guided by
      hyperconjugation of the carbocationic 2p orbital with parallel C-C and C-H bonds.
      Hyperconjugation for cations with a horizontal 2p orbital (in the plane of the
      ABCD ring system) leads to annulation and ring expansion. If the 2p orbital
      becomes vertical, hyperconjugation fosters 1,2-methyl and hydride shifts.
      Transition states leading to rings D and E were bridged cyclopropane/carbonium
      ions, which allow ring expansion/annulation to bypass formation of undesirable
      anti-Markovnikov cations. Similar bridged species are also involved in many
      cation rearrangements. Our calculations revealed systematic errors in DFT
      cyclization energies. A spectacular example was the B3LYP/6-311+G(2d,p)//B3LYP/6
      31G* prediction of endothermicity for the strongly exothermic cyclization of
      squalene to hopene. DFT cyclization energies for the 6-311+G(2d,p) basis set
      ranged from reasonable accuracy (mPW1PW91, TPSSh with 25% HF exchange) to
      underestimation (B3LYP, HCTH, TPSS, O3LYP) or overestimation (MP2, MPW1K,
      PBE1PBE). Despite minor inaccuracies, B3LYP/6-31G* geometries usually gave
      credible mPW1PW91 single-point energies. Nevertheless, DFT energies should be
      used cautiously until broadly reliable methods are established.

PMID- 16446813
TI  - Modular multidentate phosphine ligands: application to palladium-catalyzed
      allylic alkylations.
AB  - Multidentate phosphines were readily obtained by reaction of chiral multidentate
      amines, prepared via ring opening of (S)-N-tosyl-2-isopropylaziridine with
      ammonia, primary, and secondary amines, with achiral phosphorus containing
      building blocks. The phosphines were used in palladium-catalyzed alkylation of
      rac-3-cyclohexenyl and cyclopentenyl carbonates. The enantioselectivity and
      reactivity were largely dependent on the structure of the amine core of the
      ligands. Up to 88% ee was observed in reactions with the six-membered substrate.

PMID- 16446814
TI  - Nucleoside synthesis from 3-alkylated sugars: role of 3beta-oxy substituents in
      directing nucleoside formation.
AB  - Using Vorbruggen's protocol, reaction of persilylated uracil with xylofuranose
      derivatives having 3beta-oxy-3alpha-alkyl substitution produced both alpha- and
      beta-nucleosides. Only the beta-nucleosides were formed from substrates having
      the reverse stereochemistry at C-3 or lacking the 3-alkyl substituent.
      Participation of the 3beta-oxy substituent in stabilizing the incipient C-1
      carbonium ion (or oxonium ion) intermediate has been suggested from analysis of
      energy-minimized conformations.

PMID- 16446815
TI  - Oxoketene-oxoketene, imidoylketene-imidoylketene and oxoketenimine-imidoylketene
      rearrangements. 1,3-Shifts of phenyl groups.
AB  - Dibenzoylketene 5 undergoes degenerate 1,3-shifts of the phenyl group between
      acyl and ketene carbon atoms, thus interconverting it with 6 and 7. This 1,3
      shift takes place in the gas phase under flash vacuum thermolysis (FVT)
      conditions, but not in solution at 110-145 degrees C. Imidoyl(benzoyl)ketene 13
      undergoes degenerate 1,3-shift of the phenyl group on FVT, thus interconverting
      it with 14, but the ketenimine isomer 15 is not formed, and none of these shifts
      take place in the solid state at 250 degrees C. Imidoyl(p-toluoyl)ketene 21
      undergoes a 1,3-p-tolyl shift, interconverting it with ketene 22 but not with
      ketenimine 23. The imidoyl(p-toluoyl)ketene rotamer 25 cyclizes to 4
      toluoyloxyquinoline 28 and 4-quinolone 29. The cyclization of
      imidoyl(benzoyl)ketene 13 to 4-benzoyloxyquinoline 18, and of 25 to 28 involves
      1,3-C-to-O shifts of benzoyl (toluoyl) groups. Calculations of the transition
      states for the transformations at the B3LYP/6-31G** level of theory are in
      agreement with the observed reaction preferences.

PMID- 16446816
TI  - Dopamine selective molecularly imprinted polymers via post-imprinting
      modification.
AB  - A novel synthetic dopamine receptor bearing bidentate binding sites were prepared
      by covalent imprinting using a disulfide linkage which is cleaved and oxidized to
      a non-covalent sulfoxide recognition group. The used templates have dopamine-like
      structures connected to an allyl moiety via a disulfide and to a 4-vinylphenyl
      group via a cyclic boronic diester. After the polymerization, the ester bonds
      were hydrolyzed and the disulfide bond was reduced to remove the template moiety
      from the polymer matrix, followed by the oxidation to transform the thiol
      residues into sulfonic acid (post imprinted process). The imprinted polymer
      adsorbed dopamine selectively in aqueous solution with the two-point interaction,
      i.e. the formation of cyclic boronic diester and electrostatic interaction with
      the sulfonic acid residue.

PMID- 16446817
TI  - Synthesis of trimethyl (2S,3R)- and (2R,3R)-[2-2H1]-homocitrates and dimethyl
      (2S,3R)- and (2R,3R)-[2-2H1]-homocitrate lactones-an assay for the stereochemical
      outcome of the reaction catalysed both by homocitrate synthase and by the Nif-V
      protein.
AB  - Trimethyl (3R)-homocitrate 17, trimethyl (2S,3R)-[2-2H1]-homocitrate 17a and
      (2R,3R)-[2-2H1]-homocitrate 17b, as well as dimethyl (3R)-homocitrate lactone 18,
      (2S,3R)-[2-2H1]-homocitric lactone 18a and (2R,3R)-[2-2H1]-homocitric lactone 18b
      have been synthesised. D-quinic acid 12 was used as the source of the (3R)-centre
      in the unlabelled target compounds 17 and 18. (2)-Shikimic acid 19 and the (2)-[2
      2H]-shikimic acid derivative 32 respectively were used in the synthesis of the
      labelled compounds. In the latter syntheses, Sharpless directed epoxidation of
      the olefin in the 5-deoxy ester diols 23 and 35 ensured a reaction from the same
      face as the allylic and homoallylic alcohols, and the reduction of the protected
      epoxides 25 and 37 ensured that the label was introduced in a stereoselective
      manner. The 1H NMR spectra of the labelled products present an assay for the
      stereochemistry of the biological reactions catalysed by homocitrate synthase and
      by the protein from the nifV gene.

PMID- 16446818
TI  - Cooperative binding and self-assembling behavior of cationic low molecular-weight
      dendrons with RNA molecules.
AB  - Tri(ethylene glycol) derived, low molecular-weight dendrons with various amine
      end groups were synthesized and characterized for their properties of binding and
      self-assembling with RNA using the Candida ribozyme as a model RNA molecule.
      These dendritic compounds form stable complexes and well-defined nanoscale
      particles with RNA molecules via electrostatic interactions and self-assembly
      process, while leaving the other terminal of the tri(ethylene glycol) chain
      accessible for targeting. This suggests that dendrimers of this type hold great
      promise for specific RNA targeting and RNA delivery.

PMID- 16446819
TI  - Functionalized magnesium organometallics as versatile intermediates for the
      synthesis of polyfunctional heterocycles.
AB  - In the last few years, we have demonstrated that the halogen/magnesium-exchange
      reaction is a unique method for preparing a variety of new functionalized aryl,
      alkenyl, heteroaryl magnesium compounds which has considerably extended the range
      of functionalized Grignard reagents available for synthetic purposes. A variety
      of functional groups such as an ester, nitrile, iodide, imine and even sensitive
      groups like nitro, hydroxyl and boronic ester can be tolerated in these
      organomagnesium compounds. We wish to describe the application of this
      halogen/magnesium-exchange reaction for the preparation of a broad range of five-
      and six-membered functionalized heteroaryl magnesium compounds and their
      reactions with various electrophiles providing a new entry to a range of
      polyfunctional heterocycles such as thiophene, furan, pyrrole, imidazole,
      thiazole, antipyrine, pyridine, quinoline and uracil derivatives.

PMID- 16446820
TI  - Water-assisted fabrication of aligned microsized carbon tubes made of self
      assembled multi-wall carbon nanotubes.
AB  - Aligned micro-sized carbon tubes have been successfully synthesized on silicon
      substrate by pyrolysis of cyclohexane/ferrocene in the presence of water, a
      spectacular feature of which is that the multi-wall carbon nanotubes formed in
      situ act as the basic building blocks for the construction of micro-tubes via a
      "multi-scale" self-assembly process.

PMID- 16446821
TI  - cis-Diol functional group recognition by reactive desorption electrospray
      ionization (DESI).
AB  - Heterogeneous reactions at a solution/solid interface are utilized in an ambient
      mass spectrometry experiment to recognize the cis-diol functionality by its
      selective complexation reaction to form a cyclic boronate.

PMID- 16446822
TI  - Total synthesis of floresolide B and Delta(6,7)-Z-floresolide B.
AB  - The total syntheses of the cytotoxin marine natural product floresolide B (1) and
      its Delta(6,7)-Z isomer (2) have been achieved through an olefin metathesis-based
      strategy.

PMID- 16446823
TI  - Chloride ion efflux from liposomes is controlled by sidechains in a channel
      forming heptapeptide.
AB  - A suite of amphiphilic heptapeptides incorporating a glutamic acid derivative on
      the C-terminal side of a (Gly)(3)Pro sequence gives dramatically lower chloride
      ion release from liposomes when present in free carboxyl form rather than as an
      ester or amide.

PMID- 16446824
TI  - Colloidal and monocrystalline Ln3+ doped apatite calcium phosphate as
      biocompatible fluorescent probes.
AB  - Ultrafine individualised mono crystalline Ca(10-x)(PO4)(6-x)(HPO4)x(OH)(2-x)
      deficient calcium hydroxyapatite nanocrystals displaying fluorescence under
      visible excitation are proposed for utilisation as biocompatible biological
      probes.

PMID- 16446825
TI  - Completely miscible disc and rod shaped molecules in the nematic phase.
AB  - Disc and rod shaped molecules which are completely miscible in the nematic phase
      were synthesised and the miscibility behaviour was investigated and confirmed by
      POM, DSC and XRD studies.

PMID- 16446828
TI  - Organic rectifying junctions fabricated by ionic coupling.
AB  - Ionically-assembled structures that comprise discrete layers of cationic
      acceptors (4,4'-bipyridinium) and anionic donors (copper phthalocyanine
      3,4',4'',4'''-tetrasulfonate) exhibit asymmetric current-voltage (I-V)
      characteristics with high rectification ratios of 60-100 at +/-1 V.

PMID- 16446827
TI  - Iridium-complex modified CdSe/ZnS quantum dots; a conceptual design for bi
      functionality toward imaging and photosensitization.
AB  - We report the design and synthesis of Ir-complex functionalized CdSe/ZnS quantum
      dots (QDs), in which the QD plays a key role in imaging, while the Ir-complex
      acts as a sensitizer to produce singlet oxygen; this conceptual design presents a
      novel scheme in both bio-imaging and photodynamic therapy.

PMID- 16446826
TI  - Cooperative AND receptor for ion-pairs.
AB  - A novel heteroditopic calix[4]diquinone receptor capable of binding an anion and
      cation simultaneously in a cooperative fashion is shown only to recognise halide
      anions in the presence of a suitable cobound cationic guest species, and displays
      affinity for certain ion-pairs where no affinity for either of the free ions is
      observed.

PMID- 16446829
TI  - A molecular pinwheel multicopper(I) cluster, [(L(S-))6Cu(I)13(S2-)2]3+ with mu4
      sulfido, mu3-thiolato and nitrogen ligands.
AB  - A copper(I) complex with new N2S thiol ligand transforms to a multicopper(I)
      cluster, [(L(S-))6Cu(I)13(S2-)2]3+ (1); its X-ray structure exhibiting mu4
      sulfido and mu3-thiolato coordination is presented and compared to other cuprous
      thiolato/sulfido clusters including that observed in the copper enzyme nitrous
      oxide reductase.

PMID- 16446830
TI  - Naked-eye detection of fluoride ion in water: a remarkably selective easy-to
      prepare test paper.
AB  - A test paper for high-selectivity detecting fluoride ion in natural aqueous
      environments without any spectroscopic instrumentation was achieved by using Ru
      bipy based quinonehydrazone as a chromo- and fluorogenic hybrid chemosensor.

PMID- 16446831
TI  - One-pot cross-metathesis/tandem carbonyl ylide formation-intramolecular
      cycloaddition of an unsaturated 2-diazo-3,6-diketoester.
AB  - Dicarbonyl-stabilised diazo functionality is tolerated during alkene cross
      metathesis using Grubbs' catalyst, but undergoes subsequent tandem carbonyl ylide
      formation-intramolecular 1,3-dipolar cycloaddition on addition of catalytic
      Rh2(OAc)4 in a one-pot operation.

PMID- 16446833
TI  - Palladium-catalyzed addition of alkynes to cyclopropenes.
AB  - The palladium catalyzed coupling of alkynes and cyclopropenes provides a powerful
      method for the synthesis of alkynylcyclopropanes, proceeding under mild
      conditions in the presence of many functional groups (such as esters, carboxylic
      acids, aldehydes, and alcohols).

PMID- 16446832
TI  - Lithocholic acid analogues, new and potent alpha-2,3-sialyltransferase
      inhibitors.
AB  - A new type of noncompetitive alpha-2,3-sialyltransferase inhibitor has been
      synthesized; we report the discovery, preparation and inhibitory activity of
      sixteen lithocholic acid analogues.

PMID- 16446834
TI  - Highly enantioselective DNA-based catalysis.
AB  - A new approach to DNA-based asymmetric catalysis is presented, which gives rise
      to very high enantioselectivities (up to 99% ee) in the copper catalyzed Diels
      Alder reaction in water.

PMID- 16446835
TI  - Novel cyclization reaction of 1,omega-diiodo-1-alkynes without the loss of iodine
      atoms.
AB  - In the presence of 1-hexynyllithium (0.2-0.6 equiv.), 1,omega-diiodo-1-alkynes
      undergo a new type of cyclization reaction without the loss of two iodine atoms
      to afford (diiodomethylene)cycloalkanes.

PMID- 16446836
TI  - Influence of anellation in N-heterocyclic carbenes: novel quinoxaline-anellated
      NHCs trapped as transition metal complexes.
AB  - The synthesis, NMR-, and crystal structure data of novel electron-deficient
      quinoxaline anellated imidazol-2-ylidene precursors and complexes thereof are
      reported and compared with related less electron-withdrawing or non-anellated N
      heterocyclic carbenes and complexes to illustrate anellation effects.

PMID- 16446837
TI  - Solvent and ligand partition reaction pathways in nickel-mediated carboxylation
      of methylenecyclopropanes.
AB  - Methylenecyclopropanes are carboxylated with gaseous carbon dioxide in the
      presence of a stoichiometric amount of a nickel complex; the reaction pathways
      are significantly influenced by the reaction solvent and the amine ligand.

PMID- 16446838
TI  - Do ion tethered functional groups affect IL solvent properties? The case of
      sulfoxides and sulfones.
AB  - The covalent incorporation of functional groups-specifically sulfoxide and
      sulfone-into the cation of imidazolium ionic liquids leads to significant,
      quantifiable changes in solvent parameters which in turn have important effects
      on the bulk properties of the materials.

PMID- 16446839
TI  - Rapid generation of molecular complexity using "hybrid" multi-component reactions
      (MCRs): application to the synthesis of alpha-amino nitriles and 1,2-diamines.
AB  - Methyleneaziridines can be converted into a wide range of 1,2-diamines and 2
      cyanopiperidines in a single operation with the formation of three intermolecular
      carbon-carbon bonds using a "hybrid" MCR.

PMID- 16446840
TI  - Fluorinase mediated C-(18)F bond formation, an enzymatic tool for PET labelling.
AB  - The fluorinase enzyme from S. cattleya is applied as a catalyst for the efficient
      incorporation of [18F]-fluoride into [18F]-5'-fluoro-5'-deoxyadenosine, [18F]-5'
      fluoro-5'-deoxyinosine and [18F]-5-fluoro-5-deoxyribose for positron emission
      tomography (PET) applications.

PMID- 16446841
TI  - A direct organocatalytic entry to sphingoids: asymmetric synthesis of D-arabino-
      and L-ribo-phytosphingosine.
AB  - The organocatalytic asymmetric synthesis of D-arabino- and L-ribo
      phytosphingosine is described employing a diastereo- and enantioselective (S)
      proline-catalyzed aldol reaction of 2,2-dimethyl-1,3-dioxan-5-one and
      pentadecanal as the key step.

PMID- 16446842
TI  - The preparation of a phosphorus doped silicon film from phosphorus containing
      silicon nanoparticles.
AB  - Phosphorus containing and octyl-terminated silicon nanoparticles (NPs) are
      generated by a solution reduction route under room temperature conditions for the
      first time and characterized by TEM, HRTEM, EDX, 1H/13C/31P NMR, EPR, and PL
      spectroscopy, then annealed to form a thin film with phosphorus doping confirmed
      by microprobe elemental analyses.

PMID- 16446843
TI  - Isoindoles and dihydroisoquinolines by gold-catalyzed intramolecular
      hydroamination of alkynes.
AB  - The title compounds are enantioselectively synthesized in just two preparative
      steps, making use of the Ugi-four-component reaction with an amino acid as chiral
      component, followed by a gold-catalyzed hydroamination.

PMID- 16446844
TI  - Highly enantioselective Pd-catalyzed allylic alkylation using new chiral
      ferrocenylphosphinoimidazolidine ligands.
AB  - New ferrocenylphosphinoimidazolidines containing central chirality and planar
      chirality were found to act as highly effective chiral ligands in Pd-catalyzed
      asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl
      malonate.

PMID- 16446845
TI  - An unusual approach to spirolactones and related structures.
AB  - Spirocyclic structures can be obtained by an ipso-type radical cyclisation onto a
      furan or a suitably substituted pyrrole followed by oxidation of the stabilised
      radical adduct.

PMID- 16446846
TI  - Acyclic diaminocarbenes: simple, versatile ligands for cross-coupling reactions.
AB  - Acyclic diaminocarbenes are found to be useful ligands for palladium catalyzed
      Suzuki-Miyaura, Sonogashira and Heck cross-coupling reactions of aryl/alkenyl
      bromides and chlorides.

PMID- 16446847
TI  - Structure and properties of a new double-stranded tetranuclear [Cu(II)2]2
      helicate.
AB  - A novel double-stranded tetranuclear helicate composed of a pair of [Cu(II)(2)]
      dimers has been prepared and characterized by exploiting the flexibility,
      chelating ability and bridging potential of a hexadentate bis-oximate ligand.

PMID- 16446848
TI  - A concise enantioselective synthesis of iminosugar derivatives.
AB  - The concise de novo synthesis of amino- and iminosugar derivatives is presented;
      the four stereocenters of the iminosugar derivatives are created in two-steps
      with high chemoselectivity and excellent enantioselectivity.

PMID- 16446849
TI  - [Stroke units in Chile].
AB  - Stroke is a major public health problem in Chile, with an incidence similar to
      that of many industrialized nations, it accounts for 10% of all deaths and ranks
      5th in number of healthy years of life lost to a disease. Organized inpatient
      care for stroke patients has been shown in systematic reviews of randomized
      clinical trials to be effective in preventing death, disability and institutional
      care, without increasing length of stay compared to usual care. Organized stroke
      unit care is provided by multidisciplinary teams that exclusively manage stroke
      patients in a dedicated ward (stroke ward) of which there are various possible
      models; acute stroke units which accept patients acutely but discharge early
      (usually within 7 days). This could include an "intensive" model of care with
      continuous monitoring and high nurse staffing levels; comprehensive (i.e.
      combined acute and rehabilitation) stroke units which accept patients acutely but
      also provide rehabilitation for at least several weeks if necessary. The way in
      which stroke units affect outcome is through reduction of complications of
      immobility and probably non specific neuroprotection. Stroke units should deliver
      high quality evidence based interventions to all eligible patients and should
      maintain high standards of care through staff training, guidelines and protocols,
      audit and quality assurance. Given that stroke is one of the fifty six health
      priorities in the health reform, inpatient stroke care should be delivered
      through stroke units organized in hospitals throughout Chile.

PMID- 16446850
TI  - [Cerebrovascular disease in a Neurologic Intermediate Care Unit in Chile.
      Analysis of 459 consecutive patients].
AB  - BACKGROUND: Stroke is the second cause of mortality and the first cause of
      morbidity in Chile and worldwide. Nowadays there is a major interest in
      introducing new therapies applying evidence based medicine for these patients.
      AIM: To describe the clinical profile of patients attended after a stroke, to
      determine stroke subtypes and their risk factors. MATERIAL AND METHODS:
      Retrospective review of clinical records of 459 patients (mean age 65+/-48 years,
      238 female) that were admitted to our unit during a period of 37 months. RESULTS:
      Sixty three percent of patients had an ischemic stroke, 14% had an hemorrhagic
      stroke, 15% had a transient ischemic attack, 2% had a cerebral venous thrombosis
      and 6% a subarachnoidal hemorrhage. The global mortality was 1%. Seventy percent
      of patients had a history of high blood pressure. CONCLUSIONS: The most common
      type of stroke is ischemic and high blood pressure is the main risk factor.

PMID- 16446852
TI  - [Inflammatory bowel disease: experience of two Chilean centers].
AB  - BACKGROUND: The incidence of Inflammatory Bowel Disease (IBD) has increased,
      particularly in the developed world, and probably also in Chile. AIM: To report
      our experience with a large group of patients from two medical centers, Hospital
      Clinico de la Universidad de Chile (HCUCH) and Clinica Las Condes (CLC) and to
      characterize the clinical features of IBD in Chile. PATIENTS AND METHODS:
      Retrospective review of 238 patients with IBD (age range 14-78 years, 143 women)
      treated at HCUCH and CLC between January 1990 and August 2002. RESULTS: One
      hundred eighty one patients had ulcerative colitis (UC) and 57 had Crohn's
      disease (CD), with an UC/CD ratio of 3.2/1. Forty eight percent of patients were
      aged between 20 and 39 years old and 69% were diagnosed after 1995. Patients from
      HCUCH had more severe disease, more complications and needed surgery more often.
      CONCLUSIONS: Clinical features of Chilean patients with IBD are similar to those
      of other countries. UC is more common than EC. There is a higher proportion of
      women with the disease. The severity of the disease was higher among HCUCH.

PMID- 16446851
TI  - [Coronary biomarkers and long-term clinical outcome in acute coronary syndrome
      without ST segment elevation].
AB  - BACKGROUND: The use of new biomarkers improved risk stratification for patients
      with acute coronary syndromes (ACS). AIM: To evaluate the relationship between
      multiple biomarkers and long-term clinical outcome in ACS without ST segment
      elevation. PATIENTS AND METHODS: Consecutive patients presenting with suspected
      ACS were studied. On admission to the emergency room, serum was obtained to
      determine highly sensitive C reactive protein (hsCRP), erythrocyte sedimentation
      rate (ESR), lipoprotein (a) (LPa) and soluble P selectin (sPS). Clinical
      endpoints were mortality and a composite endpoint of major adverse cardiovascular
      events (MACE) including death, re-infarction, and angina. RESULTS: Seventy
      patients, aged 63+/-13 years, 54 males, were studied. Final diagnosis was
      unstable angina in 71% and non-ST-segment elevation myocardial infarction in 29%.
      MACE and mortality rate were 17% and 5.8%, respectively. We found higher plasma
      levels of hsCRP, ESR and Lp(a) in patients with MACE (p=0.032, p=0.015 and
      p=0.010, respectively). Plasma levels of hsCRP and ESR were also higher in
      patients who died during the follow up (p=0.002 y p=0.045, respectively).
      CONCLUSION: Plasma levels of inflammatory markers and atherosclerosis biomarkers
      are associated with a worse long-term clinical outcome in ACS without ST segment
      elevation. The inclusion of these biomarkers in the routine blood test on
      admission, could improve risk stratification of patients with ACS in the future.

PMID- 16446853
TI  - [Pathological characteristics of thyroid microcarcinoma. A review of 402
      biopsies].
AB  - BACKGROUND: Thyroid microcarcinoma is a tumor of 10 mm or less, that should have
      a low risk of mortality. However, a subgroup of these carcinomas is as aggressive
      as bigger tumors. AIM: To describe the pathological presentation of these tumors,
      and compare them with larger tumors. MATERIAL AND METHODS: All pathological
      samples of thyroid carcinoma that were obtained between 1992 and 2003, were
      studied. In all biopsies, the pathological type, tumor size, the focal or
      multifocal character, the presence of lymph node involvement and the presence of
      lymphocytic thyroiditis or thyroid hyperplasia, were recorded. RESULTS: One
      hundred eighteen microcarcinomas and 284 larger tumors were studied. The mean age
      of patients with microcarcinoma and larger tumors was 42.7+/-14 and 49.3+/-16
      years respectively (p <0,001) and 83% were female, without gender differences
      between tumor types. Mean size of microcarcinomas was 8.6 mm and 116 (98%) were
      papillary carcinomas. Of these, 109 (94%) were well differentiated and seven (6%)
      were moderately differentiated. Thirty six (31%) were multifocal and in 10
      (8,6%), there was lymph node involvement. The mean size of larger tumors was 23.8
      mm and 241 (85%) were papillary carcinomas. Of these, 200 (83%) were well
      differentiated, and 41 (17%) were moderately differentiated. Eighty five (35%)
      were multifocal and in 44 (18%) there was lymph node involvement. The prevalence
      of thyroiditis and hyperplasia was significantly higher among microcarcinomas
      than in larger tumors (15 and 2.5%, respectively, p <0.001, for the former; 32.4
      and 1.7%, respectively, p <0.001, for the latter). CONCLUSIONS: In this series,
      one third of microcarcinomas were multifocal and 10% had lymph node involvement.
      Therefore, the aggressiveness of these tumors is higher than what is reported in
      the literature and they should be treated with total thyroidectomy.

PMID- 16446854
TI  - [Factors associated with the severity of liver damage in chronic hepatitis C].
AB  - BACKGROUND: Twenty percent of patients with chronic hepatitis C evolve to
      cirrhosis in 10 to 20 years. The degree of steatosis and hepatic iron stores in
      liver biopsy increase the risk. Age, high body mass index, diabetes mellitus and
      alcohol consumption are factors associated to the severity of liver damage. AIM:
      To study the association of steatosis and increased iron stores in the liver
      biopsy and age, overweight, alcohol consumption and diabetes with the severity of
      liver damage in patients with hepatitis C virus infection. PATIENTS AND METHODS:
      Retrospective study of 84 liver biopsies of patients with chronic infection with
      hepatitis C virus were studied. The pathological appearance was classified as
      stage I when chronic hepatitis with mild activity without fibrosis was observed;
      as stage II when moderate chronic hepatitis with mild fibrosis was observed and
      as stage III when there was a moderate chronic hepatitis with fibrosis or
      cirrhosis. The amount of steatosis and iron deposition in the biopsy were also
      assessed. RESULTS: Forty one percent of patients were in stage I, 32% in stage II
      and 27% in stage III. Patients in stage I were younger than those in stages II
      and III (40.7 and 52.2 years respectively, p <0,001). No association between the
      severity of liver damage and the degree of steatosis, hemosiderosis, body mass
      index or alcohol intake, was observed. The frequency of diabetes mellitus
      increased along with pathological staging (3, 15 and 30% in stages I, II and III,
      respectively, p <0,05). CONCLUSIONS: This study confirms that severity of chronic
      hepatitis C is associated with age and the presence of diabetes mellitus.

PMID- 16446855
TI  - [Adult celiac disease: clinical experience].
AB  - BACKGROUND: The prevalence of celiac disease (CD) is unknown in Chile. We have
      recently noted a rise in the number of cases diagnosed among adults. AIM: To
      describe the clinical characteristics of a group of adult celiac patients.
      PATIENTS AND METHODS: Clinical data of patients older than 15 years with positive
      antitransglutaminase or antiendomysial autoantibodies and a duodenal biopsy
      characteristic of CD were retrospectively reviewed. Age at diagnosis, symptoms
      and signs and laboratory, endoscopic and histological findings, were analyzed.
      RESULTS: Thirty seven patients (28 women), were studied. Median age at diagnosis
      was 41 years (range 15-69). Main symptoms and signs were diarrhea (78%), weight
      loss (38%) and abdominal pain (38%). Anemia was found in 49%, elevation of ESR in
      57%, elevation of alkaline phosphatases in 54%, elevation of aspartate
      aminotransferase in 38% and a rise in alanine aminotransferase in 27%.
      Antiendomysial antibodies were positive in 17/22 (77%) and antitransglutaminase
      in 19/22 (86%) patients. Endoscopic findings were suggestive of CD in 47% of
      cases and duodenal biopsy showed intestinal villi atrophy in 34 (92%) patients.
      The three patients with normal histology had positive serology and a good
      response to gluten free diet. CONCLUSIONS: CD should be considered in the
      differential diagnosis of patients with unespecific digestive symptons, even when
      they present late in adult life. Serologic markers are a good diagnostic tool. A
      normal duodenal pathology does not exclude the diagnosis, if other diagnostic
      features are present.

PMID- 16446856
TI  - [Assessment of the management of community-acquired pneumonia in adults
      outpatients].
AB  - BACKGROUND: There is limited information about the effectiveness of the treatment
      of community-acquired pneumonia (CAP) in Chilean emergency rooms. AIM: To assess
      the treatment of CAP in emergency rooms at the Vina del Mar Health Service in
      Chile. MATERIAL AND METHODS: Prospective study of immunocompetent adult patients
      consulting for a CAP in emergency rooms. Those that required hospital admission
      were considered ineligible. The initial clinical and laboratory assessment,
      antimicrobial treatment and their condition after 30 days of follow up, were
      recorded. RESULTS: Three hundred eleven adult patients aged 57+/-22 years (152
      males), were evaluated. Patients with class I CAP (40% of cases) were treated
      with Clarithromycin (71.8%) or Amoxicillin (26.6%) for 10 days. Patients with
      class II CAP (60%) were treated with Amoxicillin-clavulanate (80.7%) or
      Levofloxacin (18.2%) for 10 days. Three hundred eight patients (99%) were cured
      without need of hospital admission; three patients (1%) were subsequently
      hospitalized because of clinical failure of ambulatory treatment. Overall, three
      patients (1%) died; all deaths occurred during or immediately after
      hospitalization and were related to the severity of lung infection but not to the
      choice of antibiotic treatment. CONCLUSIONS: The outpatient management of CAP by
      general practitioners working at emergency rooms was clinically effective with
      low rates of hospital admission and mortality.

PMID- 16446857
TI  - [Genetic, clinical and molecular analysis of a family affected by amelogenesis
      imperfecta].
AB  - BACKGROUND: Amelogenesis Imperfecta (AI) is a group of conditions where there is
      an abnormal formation of enamel in terms of quantity, structure and composition.
      AI is clinically and genetically heterogeneous, there are sex linked and
      autosomal versions, dominant and/or recessive, with phenotypes of hypoplastic,
      hypocalcified or hypomature enamel. Only recently, through clinical, genetic and
      molecular studies of affected families, phenotypic-genotypic correlations are
      being established in this group of anomalies. AIM: To carry out a genetic,
      clinical and molecular analysis of a Chilean family affected with an enamel
      malformation, which probably would correspond to Amelogenesis Imperfecta Dominant
      Autosomal (AIDA), of hypoplastic type, resulting from g.6395G>A mutation in the
      enamelin gene. PATIENTS AND METHODS: A genealogical pattern was created for five
      generations. Five members of this family group were clinically examined, and four
      of them had a molecular analysis that consisted of the detection of a mutation in
      the enamelin gene using PCR. RESULTS: In this family, the enamel malformation
      presents a dominant autosomal pattern of inheritance. The clinical examination of
      the group allowed a diagnosis of Amelogenesis Imperfecta, of the hypoplastic
      local type. However, the molecular analysis revealed that the members analyzed
      did not exhibit the g.6395G>A mutation reported for the enamelin gene (ENAM).
      CONCLUSIONS: The enamel phenotype in this family could be explained by the
      presence of one of four other mutations recently described in this or another
      gene, thereby supporting the findings of allelic heterogeneity reported in the
      literature.

PMID- 16446858
TI  - [Plasma C reactive protein in elective orthopedic surgery].
AB  - BACKGROUND: C reactive protein (CRP) is used as a marker of inflammatory,
      infectious and surgical processes. AIM: To measure post operative plasma CRP
      levels after elective orthopedic surgery. MATERIALS AND METHODS: Four groups of
      25 patients each were defined according to the type of surgical procedure
      performed. Group I corresponded to pure arthroscopic meniscectomy. Group II to
      arthroscopic anterior cruciate ligament reconstruction or knee osteotomy. Group
      III to elective primary total hip or knee arthroplasty and group IV to
      instrumented elective spine surgery. Plasma CRP levels were measured
      prospectively at the preoperative day and at the 1st, 2nd, 3rd, 7th and 15th
      postoperative day. Patients that had any complication were evaluated
      independently. RESULTS: In all uncomplicated patients, a similar shape and
      distribution of plasma CRP curves were observed, with maximum postoperative
      levels observed between the second and third day. Patients with more complex
      surgical procedures had higher CRP values. In all groups, CRP levels decreased
      significantly at 7th and 15th day, with respect to the higher measured value. In
      patients with surgical complications, PCR values were higher or did not decrease
      significantly at the seventh postoperative day, as in patients without
      complications. CONCLUSION: Plasma CRP levels fluctuate after elective orthopedic
      surgical procedures, with maximum values observed between the 2nd and 3rd
      postoperative day followed by an ulterior decrease. This behavior changes if
      postoperative complication appear. Serial measurements of CRP levels may be
      useful in the early detection of surgical complications.

PMID- 16446859
TI  - [Successful treatment of idiopathic acquired refractory thrombotic
      thrombocytopenic purpura with an association of rituximab-vindesine. Report of
      one case].
AB  - We report a 23 years old female who presented a second episode of thrombotic
      thrombocytopenic purpura (TTP). She was treated with fresh frozen plasma
      infusions and 14 plasma exchange (PE) sessions without response. Therefore a
      second-line therapy was started, associating a weekly cycle administration of
      vindesine (Vds) 2 mg/m2 and rituximab (R) 375 mg/m2. Five cycles of this
      association plus one cycle of R exclusively, were administered. After the third
      course, biological signs of improvement were observed and complete normalization
      of blood cell counts and other specific parameters was seen after 8 weeks. From
      the beginning of her second relapse we detected a severe deficit (<5%) in von
      Willebrand-cleaving factor (ADAMTS13) associated to the presence of ADAMTS13
      inhibitors. The combined treatment induced an improvement in ADAMTS13 values
      without detectable inhibitors. After 21 months of follow-up the patient was well,
      without signs of relapse but ADAMTS13 values were still under normal, which may
      be an unfavorable prognostic factor. PE is the treatment of choice for acquired
      idiopathic TTP, but for refractory cases or TTP cases with severe ADAMTS13
      values/high inhibitor titers, PE associated to an immunosuppressive treatment
      should be considered.

PMID- 16446861
TI  - [Small intestinal bacterial overgrowth. An update].
AB  - Small intestinal bacterial overgrowth (SIBO) is characterized by nutrient
      malabsorption, associated with an excessive number of bacteria in the proximal
      small intestine. Unfortunately, the diagnosis of bacterial overgrowth presents
      several difficulties and limitations, and as yet there is not a widespread
      agreement on the best diagnostic test. SIBO occurs when there are alterations in
      intestinal anatomy, gastrointestinal motility, or a lack of gastric acid
      secretion. The true association between SIBO and irritable bowel syndrome and
      celiac disease remains uncertain. The treatment usually consists in the
      eradication of bacterial overgrowth with repeated courses of antimicrobials,
      nutritional support and when it is possible, the correction of underlying
      predisposing conditions.

PMID- 16446860
TI  - [Aneurysmal bone cyst of the maxilla. Report of one case].
AB  - Aneurysmal bone cysts are benign fibro osseous lesions, rarely present in
      maxillary region. We report the CT and morphological findings of aneurysmal bone
      cyst of the maxilla in a 15 years old female. The patient was subjected to a
      maxillectomy, preserving the orbit floor. The postoperative evolution has been
      uneventful. The tumor mainly involved the maxillary sinus with extension to the
      orbit wall and osseous palate. Very few cases of aneurysmal bone cysts of the
      maxilla have been reported in the literature.

PMID- 16446862
TI  - [Diagnosis and management of endocrine emergencies in pediatrics].
AB  - The study of endocrine emergencies in childhood is important due to their high
      mortality and residual morbidity, that can be reduced with an adequate diagnosis
      and/or therapy. In this article, we review hypoglycemia, adrenal crisis,
      hypocalcemia, hypercalcemia and thyroid storm in children, with focus on initial
      diagnostic approach and management.

PMID- 16446863
TI  - [Virginia Woolf as an example of a mental disorder and artistic creativity].
AB  - This is an attempt to evaluate the mental disorder that the novelist Virginia
      Woolf suffered, and to determine the relationship between her creativity and her
      insanity. What mostly characterizes her illness is the presence of typical phases
      of severely impairing depression and significant hypomania, culminating in
      suicide at the age of 59. This is a convincing life history of a bipolar II
      disorder, although the "broad bipolar spectrum" is less easy to define
      operational than bipolar disorder I. She was moderately stable as well as
      exceptionally productive from 1915 until she committed suicide in 1941. Virginia
      Woolf created little or nothing while she was unwell, and was productive between
      attacks. A detailed analysis of her own creativity over the years shows that her
      illnesses were the source of material for her novels.

PMID- 16446864
TI  - [Accidents in pediatrics: opportunities for prevention].

PMID- 16446865
TI  - [Distribution of alleles of the VNTR polymorphism in the 3'-untranslated region
      of the DAT1 gene (SLC6A3) in Sao Paulo/Brazil and its importance to genetic
      studies of neuropsychiatric disorders in ethically admixed populations].

PMID- 16446867
TI  - [Eating and affective disorders: a comparative study].
AB  - BACKGROUND: The relationship between eating disorders and affective disorders
      still remains unclear. Eating disordered patients may have affective disorders
      and vice versa, depressed and maniac patients may experience eating problems.
      AIM: To compare eating symptoms, attitudes and behaviors in patients with
      affective disorders and normal subjects. SUBJECTS AND METHODS: A structured
      clinical interview, the Eating Attitudes Test (EAT-40) and the Eating Disorder
      Inventory (EDI) were administered to 194 patients that fulfilled the DSM-IV
      diagnostic criteria for eating disorders, to 45 patients with affective disorders
      and to 82 normal female students. RESULTS: Patients with eating disorders ranked
      significantly higher on the EAT-40 and on the EDI and its factors (p <0.001).
      Patients with affective disorders ranked between eating disordered patients and
      the students (p <0.001). Compulsive-purgative type of anorectics and purgative
      type of bulimics showed the highest scores on these measures (p <0.001).
      Restrictive type of anorectics scored significantly highest on EDI maturity fears
      item (p <0.001). Not significant difference was observed on the EDI
      ineffectiveness item, between purgative bulimics and depressive patients and
      between the latter and compulsive-purgative anorexics, on the EDI interpersonal
      distrust item. CONCLUSIONS: Compulsive-purgative type of anorectics and purgative
      type of bulimics showed the more severe psychological and behavioral
      disturbances. Restrictive types of anorectics were the most immature. Both
      purgative bulimics and depressive patients showed feelings of general inadequacy,
      and both compulsive-purgative anorexics and depressive patients displayed an
      interpersonal distrust. As a whole, patients with affective disorders did not
      show the core eating disordered behaviors and attitudes as seen in patients
      suffering from eating problems.

PMID- 16446868
TI  - [Microsatellite marker AGAT of the mineralocorticoid receptor gene is associated
      with plasma renin activity in patients with essential hypertension].
AB  - BACKGROUND: Hypertensive states could result from constitutive activation of
      mineralorticoid receptor (MR) that generates salt retention and blood pressure
      elevation. Moreover, microsatellite regions can be associated to the regulation
      of the gene expression, producing subtle pathologies. AIM: To determine the
      influence of microsatellite marker AGAT of the mineralocorticoid receptor gene in
      the plasma renin activity (PRA) and serum aldosterone (SA) levels of essential
      hypertensives (HT). PATIENTS AND METHODS: We studied 292 HT patients and 57
      normotensive (NT) controls. Blood samples were collected for PRA, SA and DNA
      isolation. Subjects were genotyped according to the length of the tetranucleotide
      AGAT repeat using polymerase chain reaction and polyacrylamide gel
      electrophoresis. Based on the normal distribution, we considered 13 to 15 repeats
      as a habitual (H) length and less than 13 or more than 15 repeats, as non
      habitual (non-H). RESULTS: We detected 8 different lengths in the AGAT repeat
      (allele) in both groups, ranging from 9-17 repeats, where the allele 11 was not
      detected in either hypertensive or normotensive groups. The allelic distribution
      was different in both groups (c2 =37.57, 4GL, p <0.001). In hypertensive
      patients, the H group showed higher PRA levels (median (Q1-Q3)) than the non-H
      group: 1.3 (0-7-3.5) vs 1.0 (0.5-2.3) ng/mL*h, p <0.05. The SA levels did not
      show differences between both groups, but the SA*PRA product was higher in the H
      group than the no-H group: 9.3 (3.0-24.6) vs 6.5 (2.5-14.6) p <0.05. In
      normotensive patients, no differences were observed in PRA, SA and SA*PRA between
      both groups. CONCLUSION: These results show association between the length of the
      AGAT repeat with the PRA in HT, suggesting a plausible role in the control of the
      MR gene expression, and secondarily in the regulation of blood pressure.

PMID- 16446869
TI  - [Factor V Leiden and prothrombin G20210A among Chilean patients with venous and
      arterial thrombosis].
AB  - BACKGROUND: Factor V Leiden and G20210A mutation of prothrombin gene are two
      important genetic polymorphisms associated with an increased risk for thrombosis.
      AIM: To establish the prevalence of factor V Leiden and prothrombin G20210A
      mutation in the Chilean population and their association to venous and arterial
      thromboembolism. MATERIAL AND METHODS: A case-control study was conducted where
      149 patients with thrombosis (87 with arterial and 62 with venous thrombosis)
      confirmed by CAT-scan, electrocardiogram and cardiac enzymes or Doppler depending
      on the case, and 160 healthy blood donors were genetically analyzed for the
      presence of both polymorphisms. RESULTS: Factor V Leiden mutation was found in
      5.4% of patients and in 1.3% of healthy controls (p=0.04). Heterozygosity for
      G20210A prothrombin mutation was found in 5.4% of patients and in 2.5% of the
      control group (p=NS). When arterial and venous thrombosis were considered as
      separate entities, 4.6% of patients with arterial thrombosis and 6.5% with venous
      thrombosis presented factor V Leiden (p=NS). Likewise, 8.1% of patients with
      venous thrombosis and 3.5% of patients with arterial thrombosis had G20210A
      prothrombin mutation (p=NS). CONCLUSIONS: In non selected consecutive Chilean
      patients with arterial and venous thrombosis the frequency of factor V Leiden and
      prothrombin G20210A is less than we could expect from their prevalence in the
      general population.

PMID- 16446870
TI  - [Frequency of K-ras mutation in biliary and pancreatic tumors].
AB  - BACKGROUND: The ras gene family (H-ras, N-ras and K-ras) are oncogenes that
      mutate frequently in human cancer, specially in tumors of the biliary tract and
      pancreas. AIM: To determine the frequency of K-ras gene codon 12 mutation in
      pancreatic and biliary tumors. MATERIAL AND METHODS: Samples of 35 gallbladder,
      15 ampulla of Vater, 10 biliary tract and 9 pancreatic tumors, were analyzed. The
      tumor tissue was microdissected from paraffin embedded biopsies. The mutation was
      detected by a combination of polymerase chain reaction (PCR) and restriction
      fragment length polymorphism (RFLP). RESULTS: Overall, 46% of samples had K-ras
      gene mutations. Mutation frequency was 80, 56, 50 and 29% for ampulla of Vater,
      pancreatic, biliary tract and gallbladder tumors, respectively. When compared
      with the rest, gallbladder tumors had a significantly lower frequency of the
      mutation. Median survival for biliary tract tumors was 6 months, compared with 65
      months for gallbladder tumors (p <0.05). CONCLUSIONS: Gallbladder carcinoma had
      the lower frequency of K-ras mutation, when compared with pancreatic, biliary
      tract and ampulla of Vater tumors.

PMID- 16446872
TI  - [Delirium in Chilean elderly inpatients: an overlooked problem].
AB  - BACKGROUND: Delirium is a common underdiagnosed and undertreated problem in
      elderly inpatients, associated to higher morbidity, mortality and health cost.
      AIM: To evaluate the prevalence of delirium at hospital admission in medically
      ill elderly patients and the attending physician's diagnosis and treatment of
      delirium. PATIENTS AND METHODS: In a prospective and descriptive study,
      consecutive patients aged 65 years or more, admitted to an internal medicine ward
      were evaluated by independent physicians, during the first 48 h of admission, to
      asses the presence of delirium. Diagnosis of delirium was based on the Confusion
      Assessment Method. Medical and nurse records were reviewed. Family was
      interviewed when necessary. RESULTS: One hundred eight patients (52% women, age
      range 65-94 years) with an APACHE II score of 11.6+/-5, were evaluated. Fifty
      seven patients (53%) had delirium (32% hyperactive, 72% hypoactive and 5% mixed).
      Delirium prevalence was significantly higher in older patients (66% among those
      aged 75 years or older versus 30% in younger, p <0.05) and among patients with
      more severe conditions (88% among those with an APACHE score over 16 versus 47%
      below that value, p <0.05). Medical records of patients with delirium showed that
      this diagnosis was present only in 32% and cognitive deficit was described in
      73%. Ten percent of patients with delirium received sedative medication and 38%
      were physically restricted. There were no environmental interventions to prevent
      or control delirium. CONCLUSIONS: Delirium in elderly inpatients at this unit is
      an extraordinarily prevalent problem, seriously under diagnosed (68%) and under
      treated. This study should alerts our medical community to improve the diagnosis
      and management of delirium in elderly inpatients.

PMID- 16446871
TI  - [Indications, adverse effects and results of plasmapheresis in critical care
      patients].
AB  - BACKGROUND: Plasmapheresis is a therapeutic alternative for diseases in which a
      "humoral factor" has pathogenetic relevance. However it is not devoid of adverse
      effects. AIM: To review the indications, number of procedures, morbidity and
      clinical evolution of plasmapheresis in critical patients. PATIENTS AND METHODS:
      A retrospective and descriptive study in four intensive care units of an
      University hospital. The severity of patients was evaluated with APACHE II and
      SOFA scores. RESULTS: Twenty patients were studied. The most common indications
      of plasmapheresis were thrombotic thrombocytopenic purpura (TTP) in 50% of
      subjects and small vessel vasculitides in 30%. The number of procedures per
      patient oscillated between 2 and 14 (mean: 7.1+/-3.3). The registered adverse
      effects were hypocalcemia in 50% of patients, hypotension in 42.1%, coagulopathy
      in 35%, hypokalemia in 29%, rash in 20%, procedure related infections in 18% and
      fever in 10%. There was a significant decrease of 17+/-28% in prothrombin time,
      after the procedures. Seventy five percent of patients had a favorable evolution.
      Global mortality rate was 15%. All deaths occurred in patients with TTP and were
      attributed to the progression of the disease. No death was attributed to the
      procedure. The initial APACHE II and SOFA scores were 12.4+/-8.4 and 5.3+/-2.9,
      respectively. Both scores decreased after the procedure. Among other therapeutic
      measures, 15% of the patients received immunosuppressant treatment, 27% were
      dialyzed and 32% were mechanically ventilated. CONCLUSIONS: The most common
      indication of plasmapheresis was TTP. Adverse effects were frequent, however
      there was no procedure related mortality. The global mortality rate was 15% and
      all deaths occurred in patients with TTP.

PMID- 16446873
TI  - [Dialysis dose, nutrition and growth among pediatric patients on peritoneal
      dialysis].
AB  - BACKGROUND: Stunting is common among pediatric patients on peritoneal dialysis.
      AIM: To establish the best profile for urea kinetic variables associated to
      growth in children on chronic peritoneal dialysis (PD). PATIENTS AND METHODS:
      Twenty patients, aged 1 month to 14 years, 13 males, were followed for 6-12
      months, with monthly measurements of weight/age and height/age Z score; plasma
      creatinine, BUN, protein and albumin and urine and dialysate urea nitrogen,
      creatinine, protein and albumin. Minimum total Kt/V was 2.1. Dialysis dose
      (Kt/V), Protein Equivalent of Urea Nitrogen Appearance (PNA), Protein Catabolic
      Rate (PCR) and Nitrogen Balance (NB) were calculated. To identify the variable(s)
      associated to growth, the Tree Classification Model (CART) Enterprise Miner 8.1
      was applied. RESULTS: Mean total/residual Kt/V: 3.4+/-1.3/1.69+/-1.27; Daily
      Protein Intake (DPI) was 3.25+/-1.27 g/kg/day. nPNA, PCR and NB were 1.37+/-0.44,
      0.84+/-0.33 and 1.86+/-1.25 g/kg/day, respectively. Mean height/age Z score was 
      2.3+/-1.19. Eleven patients showed a positive height/age delta Z (mean 0.55+/
      0.38) and nine showed a negative growth (mean -0.50+/-0.42). The main variable
      explaining the positive growth was a Nitrogen Balance between 0.54 and 2.37
      g/kg/day, mean 1.55+/-0.21 (p <0.001). The second associated variable to growth
      was a residual Kt/V between 0.43 and 4.6 (2.02+/-0.49) (p <0.05). Kt/V and nPNA
      showed a significant correlation, but no correlation could be found between Kt/V
      and NB. CONCLUSIONS: Nitrogen Balance was the main variable associated to growth
      in pediatric PD, with values between 0.53 to 2.38 g/kg/day. The second variable
      was a residual Kt/V between 0.43 and 4.6. Therapy should be reassessed with NB
      values less than 0.54 or above 2.37 g/kg/day.

PMID- 16446874
TI  - [Presence of Bartonella henselae in cats: natural reservoir quantification and
      human exposition risk of this zoonoses in Chile].
AB  - BACKGROUND: The availability of a serologic test for cat scratch disease in
      humans has allowed the diagnosis of an increasing number of cases of this disease
      in Chile. AIM: To perform a serological survey for Bartonella henselae among cats
      in Chile. MATERIAL AND METHODS: Blood samples from 187 cats living in three
      Chilean cities were obtained. IgG antibodies against Bartonella henselae were
      measured using indirect immunofluorescence. Blood cultures were done in 60
      samples. The presence of Bartonella henselae in positive cultures was confirmed
      by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR).
      RESULTS: The general prevalence of IgG antibodies against Bartonella henselae was
      85.6%. No differences in this prevalence were found among cats younger or older
      than 1 year, or those infested or not infested with fleas. However domestic cats
      had a lower prevalence when compared with stray cats (73 and 90% respectively, p
      <0.01). Bartonella henselae was isolated in 41% of blood cultures. All the
      isolated were confirmed as Bartonella henselae by RFLP-PCR. CONCLUSIONS: This
      study found an important reservoir of Bartonella henselae in Chilean cats and
      therefore a high risk of exposure in humans who have contact with them.

PMID- 16446875
TI  - [Octreotide for bilateral chylothorax secondary to lymphoma. Report of one case].
AB  - Since chylothorax is uncommon and has multiple causes, its best treatment choice
      is not clear. Recent reports show that octreotide is useful in the treatment of
      chylothorax secondary to cancer or caused by surgical procedures. We report a 21
      years old male with a chylothorax secondary to a non Hodgkin lymphoma. Treatment
      with octreotide changed the color and triglyceride content of pleural effusion.
      Serum albumin and proteins increased and the effusion subsided after the second
      cycle of chemotherapy with CHOP. Thus octreotide was discontinued on the 27th day
      of therapy and pleural drainages were withdrawn. He was discharged in good
      conditions, 38 days after admission.

PMID- 16446876
TI  - [Pulmonary thromboembolism treated with pharmacological thrombolysis and
      mechanical fragmentation. Report of one case].
AB  - Pulmonary Embolism (PE) has a wide clinical spectrum. It is imperative to detect
      patients with a high risk to develop right ventricular failure, because this is
      the main cause of death in patients with massive PE. In this group of patients,
      invasive therapies to relieve pulmonary obstruction and right ventricle overload
      should be used as soon as possible. We report a 85 years old male with massive PE
      treated with pharmacological thrombolysis and mechanical fragmentation with an
      angioplasty balloon. Pulmonary perfusion improved significantly. Afterwards,
      systemic anticoagulation was started and an inferior vena cava filter was
      installed percutaneously. The patient was discharged in good conditions, five
      days after admission.

PMID- 16446877
TI  - [New heterodimeric nuclear receptors: key metabolic regulators with relevance in
      the pathophysiology and therapy of dyslipidemias and diabetes mellitus].
AB  - The regulation of gene expression is crucial for the normal development and the
      homeostatic maintenance of body tissues. Thus, its malfunction may determine a
      variety of human disease conditions. A growing body of evidence has shown the
      overwhelming relevance of a new class of gene expression regulators: the
      heterodimeric nuclear receptors, a family of structurally related proteins
      involved in multiple biological functions. In response to activating ligands,
      these molecules bind to specific genomic regulatory regions where they can
      coordinately modify the transcriptional activity of several genes involved in the
      main metabolic pathways of lipids and carbohydrates in cells. These functional
      properties have stimulated the study of the relationships between heterodimeric
      nuclear receptors and various disease conditions, such as dyslipidemias and
      diabetes mellitus. Here we review the experimental, clinical and epidemiological
      evidences that support the relevance of these transcriptional regulators in the
      pathophysiology of the most prevalent and lethal diseases in Western countries.
      We also explore the potential therapeutic impact of new strategies based in the
      pharmacological modulation of the heterodimeric nuclear receptors.

PMID- 16446878
TI  - [Treatment of beneficiaries of the Chilean public health system with arrhythmias
      in a University Clinical Hospital].
AB  - BACKGROUND: The costs of medical care increase along with technological advances.
      Therefore, highly complex and expensive procedures should be performed in a
      limited number of institutions. AIM: To report the initial experience on
      electrophysiological studies performed to beneficiaries of a public health
      insurance system in Chile (FONASA). MATERIAL AND METHODS: An agreement was
      reached between the Electrophysiology Unit of the Clinical Hospital of the
      Catholic University and FONASA, to perform electrophysiological studies at a
      minimal cost, that only considered disposable materials and hospital stay. Thirty
      patients with supraventricular arrhythmias or ventricular arrhythmias without an
      associated cardiopathy, were attended using this agreement at the unit. RESULTS:
      In all treated patients, arrhythmias disappeared. Costs remained within the
      assigned budget, excepting occasional complementary tests. CONCLUSIONS: This
      pioneering experience demonstrated that it is possible that public health
      insurance systems can buy complex and expensive procedures to private hospitals.

PMID- 16446879
TI  - [Biographical notes on Professor Hernan Alessandri, M.D].
AB  - Hernan Alessandri, a renowned Chilean medical educator, was born in Santiago in
      1900. He received his medical degree at the University of Chile in 1923. When in
      1927 his father, then President of Chile, was sent into exile, he used the
      opportunity to deepen his medical knowledge in France and Germany. At the
      University of Chile, he became successively Professor of Clinical Medicine
      (1932), of Medical Semiology (1937), and Full Professor and Chair of Medicine
      (1944). At the Hospital del Salvador in Santiago, he organized a Clinical
      Department exemplary for its discipline, academic environment and dedication to
      patients and students. He was one of the prime movers for the reform of medical
      teaching in 1943, created medical residency programs for the training of
      specialists in 1952, served as Dean of the Faculty of Medicine from 1958 to 1962,
      and was a founding member of the Chilean Academy of Medicine (1964). He was the
      first Latin American to be named Honorary Member of the American College of
      Physicians (1968) and became Emeritus Professor of the University of Chile in
      1973. He died in his hometown in 1982. His disciples and friends established in
      his honor a social and teaching foundation which they named after him. His
      clinical and diagnostic skills, along with his outstanding intelligence, made him
      the most brilliant clinician of his time and an exceptional medical educator who
      has inspired several generations of physicians.

PMID- 16446881
TI  - [An internship rotation in a rural area: an unforgettably positive experience for
      medical students].

PMID- 16446882
TI  - [Chilean National Board of Medicine].

PMID- 16446883
TI  - Building up tomorrow.

PMID- 16446884
TI  - Vestibular fold configuration during phonation in adults with and without
      dysphonia.
AB  - The real participation of the vestibular folds during phonation mechanism is
      unknown. How vestibular folds change their configuration during phonation is
      still unclear. Learning about these changes in the functional mechanism of
      vestibular fold would be helpful for the evaluation of pathological conditions.
      AIM: The objective of the present study was to analyze the configuration of
      laryngeal vestibular folds during phonation (sustained emission of vowel /mu/) by
      comparing exams of individuals without vocal complaints (the normal voice group)
      with those with vocal complaints. STUDY DESIGN: Transversal simple study.
      MATERIAL AND METHOD: 120 images of larynges were analyzed, 60 of normal voice
      individuals and 60 of dysphonic subjects, with equal gender distribution. The
      position of the free margin of the vestibular fold was identified in relation to
      a straight line that brought together the anterior and posterior insertions.
      Regarding this position, three types of configurations were described: concave,
      when it was in a lateral position, convex when it was in a medial position, and
      linear when it overlapped. RESULTS: Out of the 240 vestibular folds, 158 were
      concave, 41 convex and 31 linear. The concave form was predominant in both groups
      in relation to the other two forms, although the number of convex and linear
      forms increased in the dysphonic group. Analyzing the behavior of these forms in
      each gender we noticed that among women, the linear form was significantly
      increased in the dysphonic group, whereas among men there was significant
      increase in convex form. CONCLUSION: We concluded that there were differences in
      behavior of vestibular folds in the dysphonic group in relation to the normal
      voice group, and that the differences occurred differently in both gender groups.

PMID- 16446885
TI  - Comparative analysis of perceptual evaluation, acoustic analysis and indirect
      laryngoscopy for vocal assessment of a population with vocal complaint.
AB  - As a result of technology evolution and development, methods of voice evaluation
      have changed both in medical and speech and language pathology practice. AIM: To
      relate the results of perceptual evaluation, acoustic analysis and medical
      evaluation in the diagnosis of vocal and/or laryngeal affections of the
      population with vocal complaint. STUDY DESIGN: Clinical prospective. MATERIAL AND
      METHOD: 29 people that attended vocal health protection campaign were evaluated.
      They were submitted to perceptual evaluation (AFPA), acoustic analysis (AA),
      indirect laryngoscopy (LI) and telelaryngoscopy (TL). RESULTS: Correlations
      between medical and speech language pathology evaluation methods were
      established, verifying possible statistical signification with the application of
      Fischer Exact Test. There were statistically significant results in the
      correlation between AFPA and LI, AFPA and TL, LI and TL. CONCLUSION: This
      research study conducted in a vocal health protection campaign presented
      correlations between speech language pathology evaluation and perceptual
      evaluation and clinical evaluation, as well as between vocal affection and/or
      laryngeal medical exams.

PMID- 16446886
TI  - Histological analysis of tonsillectomy and adenoidectomy specimens--January 2001
      to May 2003.
AB  - Palatine and nasopharyngeal tonsils are nonencapsulated nodular masses of
      lymphoid tissue of the respiratory and digestive tract epithelium. STUDY DESIGN:
      Retrospective clinical study based on the revision of medical records of patients
      who underwent tonsillectomy and adenoidectomy at Hospital das Clinicas, Medical
      School, Marilia in the period between January 2001 and May 2003. AIM: Analysis of
      patients' profile and main pathological changes in 250 patients with palatine and
      nasopharyngeal tonsil hypertrophy, recurrent infections or both. MATERIAL AND
      METHOD: Histological review of 250 patients who underwent tonsillectomy and
      adenoidectomy among adults and children. RESULTS: Out of 250 subjects, 117
      (46.8%) were female and 133 (53.2%) were male patients. Mean age was 7.3 years,
      ranging from 2 to 34 years. Main surgical indication was concomitant presence of
      recurrent infections and hypertrophy of nasopharyngeal and palatine tonsils.
      Among these patients, 160 (64%) were classified as grades III to IV hypertrophy.
      Lymphatic or follicular lymphatic hyperplasia was observed in 205 patients (82%);
      focal inflammation was verified in 45 (18%) subjects. Among those, 2 patients
      presented squamous cell cysts, 2 had Actinomyces sp colonies and 1 cat scratch
      disease. DISCUSSION: The results presented in this study suggested a possible
      correlation between recurrent tonsillitis and palatine tonsil hypertrophy.
      CONCLUSION: Routine histological study of tonsillectomy and adenoidectomy
      specimens has a low cost-benefit rate, although, due to legal and ethical issues,
      physicians may request this type of examination.

PMID- 16446887
TI  - Comparison between radiological and nasopharyngolaryngoscopic assessment of
      adenoid tissue volume in mouth breathing children.
AB  - The pharyngeal tonsil (adenoid) constitutes the upper portion of the Waldeyer's
      ring and is located at the top of the nasopharynx, next to the auditory tube and
      choana. It plays an important role in recurrent otitis of the middle ear and many
      times its enlargement is responsible for upper airway obstruction. Tonsillectomy
      is often the treatment of choice for tonsillar diseases. So far, it is the most
      frequent and one of the oldest surgical procedures performed in children and
      young adults. The criteria for tonsillectomy, its effect on patient's
      immunological integrity and the surgical risks are widely controversial. Image
      study using paranasal sinuses x-ray is a very simple, easy and comfortable method
      to evaluate the sizes of adenoids and the grade of upper airway obstruction.
      Cohen et al. supported that paranasal sinuses x-ray is the best way to determine
      pharyngeal tonsil hypertrophy. On the other hand, nasopharyngolaryngoscopy can
      provide more accurate data on the nasopharynx, as it can dynamically reveal its
      structures and the obstruction status of the upper airway. This study compared
      the grade of adenoid hypertrophy, as well as upper airway obstruction, using the
      above-mentioned approaches in children ranging from 3 to 10 years old. The study
      came to the conclusion that nasopharyngolaryngoscopy is a much more accurate
      diagnostic procedure than radiological evaluation of the nasopharynx.

PMID- 16446888
TI  - Neck dissection in squamous cell carcinoma of the tongue.
AB  - AIM: The purpose of this study was to assess the prognosis of patients with
      tonsillar squamous cell carcinoma with different stages of lymph node involvement
      and to determine the best elective neck dissection for those cases. STUDY DESIGN:
      Case series. MATERIAL AND METHOD: 51 patients with tonsillar tumors were treated
      between 1992 and 2001. The incidence of different tumor-node-metastasis stages
      was evaluated according to primary tumor extension. RESULTS: cN0 patients had
      metastases in stages I and II only. Among pN+ subjects with stage I metastases,
      6/7 had primary tumor extending to oral cavity. CONCLUSION: Supraomohyoid neck
      dissection (stages I, II and III) is the elective treatment of choice when
      tonsillar primary tumor extends to oral cavity. When primary tumors are limited
      to the oropharynx, selective neck dissection of stages II and III proved to be
      more adequate.

PMID- 16446889
TI  - Comparative study of eminectomy and use of bone miniplate in the articular
      eminence for the treatment of recurrent temporomandibular joint dislocation.
AB  - Dislocation of the temporomandibular joint occurs when the mandibular condyle
      exits the glenoidal cavity and remains anteriorly locked to the articular
      eminence. It is repetitive (recurrent dislocation), usually associated with
      mandibular hypermobility and inclination of the articular eminence. AIM: This
      study intended to clinically and radiologically assess the technique of
      eminectomy and the use of a miniplate on the articular eminence for the treatment
      of recurrent dislocation of the temporomandibular joint of patients operated on
      at Oswaldo Cruz University Hospital from January to September 2003. STUDY DESIGN:
      Retrospective cohort. MATERIAL AND METHOD: The sample consisted of 11 patients.
      Eminectomy was performed on nine joints of five patients and the placement of a
      miniplate on the articular eminence was performed on 11 joints of six patients.
      Data collection was carried out through analysis of patient's medical charts and
      new postoperative visit. RESULTS: The results showed that there were no major
      postoperative complications with either technique. Maximum mouth opening was
      greater with eminectomy procedure and none of the patients operated on presented
      any recurrence of dislocation. CONCLUSION: It is concluded that both techniques
      were effective in the treatment of recurrent dislocation of the temporomandibular
      joint.

PMID- 16446891
TI  - Vestibular evoked myogenic potential: new perspectives in multiple sclerosis.
AB  - AIM: To evaluate vestibular evoked myogenic potentials in patients with multiple
      sclerosis as method of diagnostic support. STUDY DESIGN: Case-control. MATERIAL
      AND METHOD: We studied a group of normal individuals (n=15) and a Studied group
      (n=15) that comprised patients with diagnosis of multiple sclerosis. Both groups
      were submitted to vestibular evoked myogenic potential exam. In each ear it was
      applied 200 stimuli by clicks and repeated for 2 consecutive cycles with the
      purpose of evaluating reproducibility. The active electrode of surface was put on
      the superior S++ of sternocleidomastoid muscle and the reference electrode on the
      anterior border of the clavicle. The individuals were instructed to rotate theirs
      head to the opposite side to the stimulated ear. RESULTS: Vestibular evoked
      myogenic potential responses were prompt, reproducible and biphasic. The latency
      of wave P1 and N2 and P1-N2 amplitude showed a higher value in the studied group
      when compared with the normal group. There was no significant difference when the
      ears were compared in P1 and N2 amplitude. We noticed that individuals with
      multiple sclerosis showed no response in 30% of the cases. In evaluating the
      individuals of the Studied group with otoneurology symptoms and compared with
      individuals without symptoms, it was observed that P1 and N2 latencies and P1-N2
      amplitude were higher in symptomatic cases. CONCLUSION: Vestibular evoked
      myogenic potential was considered a good method of diagnostic support of
      vestibulospinal tract in cases of multiple sclerosis.

PMID- 16446892
TI  - Posture restrictions do not interfere in the results of canalith repositioning
      maneuver.
AB  - Benign Paroxysmal Positional Vertigo (BPPV) is a frequent cause of dizziness and
      despite of the excellent results with its treatment, there is some controversy
      about management. AIM: To assess the efficacy of Epley Maneuver with and without
      post-maneuver restrictions. STUDY DESIGN: Prospective randomized. MATERIAL AND
      METHOD: Fifty patients presenting BPPV of the posterior semicircular canal,
      treated with Epley Maneuver and divided into two groups: study group--23 patients
      -with post-maneuver restrictions, and control group--27 patients--without post
      maneuver restrictions. RESULTS: No significant difference was found between the
      studied and the control group. CONCLUSION: Post-maneuver restrictions do not
      influence the efficacy of Epley Maneuver for BPPV management.

PMID- 16446890
TI  - Balance improvement and reduction of likelihood of falls in older women after
      Cawthorne and Cooksey exercises.
AB  - Vestibular system is the absolute referential for the maintenance of balance.
      Functional deficit with aging can result in balance disturbance and in increase
      of likelihood of falls. AIM: To verify whether specific therapeutic approach of
      the system can promote motor learning and can contribute to the improvement of
      balance and to decrease of likelihood of falls. STUDY DESIGN: Clinical
      prospective. MATERIAL AND METHOD: Fifteen women, aged 60 to 69, mean = 64.8 years
      old (+/- 2.95), resident in Barra Mansa-RJ, were submitted to Cawthorne and
      Cooksey exercises during three months, three times a week, during sixty minutes.
      They were evaluated with Berg Balance Scale (BBS), whose scores determine the
      possibility of fall (PQ). RESULTS: Comparing the data obtained before and after
      intervention, we observed significant difference (p< 0.05), showing improvement
      in BBS scores and decrease in PF. CONCLUSION: Cawthorne and Cooksey exercises
      were able to promote significant improvement in the balance of this sample and
      they can be applied as prevention and treatment in balance disturbances in
      elderly people.

PMID- 16446893
TI  - Vestibular evoked myogenic potentials in affected and asymptomatic ears in
      unilateral Meniere's disease.
AB  - AIM: To verify whether vestibular evoked myogenic potentials can present
      abnormalities in the affected ear and in the asymptomatic ear in patients with
      diagnosis of unilateral Meniere's disease. STUDY DESIGN: Transversal cohort.
      MATERIAL AND METHOD: The vestibular evoked myogenic potentials of 20 patients
      with unilateral Meniere's disease were analyzed. The selection of individuals was
      based on the history and in clinical evaluation suggestive of unilaterally
      defined Meniere's disease, and with electrocochleography abnormalities in the
      affected ear. Vestibular evoked myogenic potentials were evaluated in both ears
      of each patient through absolute latencies of p13 and n23, interaural difference
      of latency of peaks p13 and n23 and amplitude p13-n23 asymmetry rate. RESULTS:
      Vestibular evoked myogenic potentials were altered in 35.0% of the affected ears
      and in 25.0% of the asymptomatic ears. The alterations were: absence of responses
      in seven cases, prolongation of p13 latency in three cases, and increase in
      interaural amplitude difference ratio in one case. CONCLUSION: The vestibular
      evoked myogenic potentials can present abnormalities in the affected and
      asymptomatic ears in patients with diagnosis of unilaterally defined Meniere's
      disease.

PMID- 16446894
TI  - Satisfaction level with hearing aid in the daily life of Army Healthcare System
      users.
AB  - The objective of the present study was to investigate satisfaction levels with
      hearing aids in daily life of Army Health System users, in addition to associated
      factors. Adults and seniors from 3rd Military Area that had purchased hearing
      aids within the years 1998 and 2003 were selected to answer SADL (Satisfaction
      with Amplification in Daily Life) questionnaire. We excluded patients aged less
      than 18 years; those that had acquired hearing aid for less than 6 weeks, and
      patients with severe comprehension and expression limitation. The results showed
      that patients were considerably satisfied with the use of aids. There was lower
      satisfaction level with the negative factor subscale of SADL (Satisfaction with
      Amplification in Daily Life), especially in relation to telephone using. The
      factors that were associated with satisfaction were linked to the person and,
      mainly, to auditory rehabilitation. The data showed that, beyond the selection of
      the most technically appropriate hearing aid, it is highly important to follow
      auditory rehabilitation programs including home trials, guidance and counseling
      so that patients can have realistic expectations.

PMID- 16446895
TI  - Update in obstructive sleep apnea syndrome in children.
AB  - The prevalence of OSAS in children is 0.7-3%, with peak incidence in pre
      schoolers. It is characterised by partial or complete upper airway obstruction
      during sleep, causing intermittent hypoxia. Both anatomical (severe nasal
      obstruction, craniofacial anomalies, hypertrophy of the pharyngeal lymphoid
      tissue, laryngeal anomalies, etc.) and functional factors (neuromuscular
      diseases) predispose to OSAS during childhood. The main cause of OSAS in children
      in adenotonsillar hypertrophy. The most common clinical manifestations of OSAS
      are: nocturnal snoring, respiratory pauses, restless sleep and mouth breathing.
      Nocturnal pulse oximetry, nocturnal noise audio/videotape recording and nap
      polysomnography are useful tools for screening suspected cases of OSAS in
      children, and the gold-standard for diagnosis is overnight polysomnography in the
      sleep laboratory. On the contrary of SAOS adults, children usually present: less
      arousals associated to apnea events, more numerous apneas/hypopneas during REM
      sleep, and more significant oxyhemoglobin desaturation even in short apneas. The
      treatment of OSAS may be surgical (adenotonsillectomy, craniofacial abnormalities
      correction, tracheostomy) or clinical (sleep hygiene, continuous positive airway
      pressure--CPAP).

PMID- 16446896
TI  - The role of matrix extracellular proteins and metalloproteinases in head and neck
      carcinomas: an updated review.
AB  - Interactions involving tumor cells and the extracellular matrix (ECM) strongly
      influence tumor development, including head and neck tumors, affecting cell
      proliferation and survival as well as the ability to migrate beyond the original
      location into other tissues to form metastases. These cell migration is often
      facilitated by partial destruction of the surrounding ECM, which is catalyzed by
      matrix metalloproteinases (MMPs), a family of more than 20 endopeptidases that is
      controlled by regulated expression of specific inhibitors (TIMPs). Several
      studies of ECM and MMPs markers have provided additional diagnostic and
      prognostic information in head and neck carcinomas. In this review, we are
      considering the role of ECM and MMPs in tumor progression, emphasizing its
      proteolytic contributors to this process, and interactions between several
      members of ECM providing substrate to regulation of this process.

PMID- 16446897
TI  - Cancer patients with large defects. Reconstructional options: a case study.
AB  - We report a case of a seventy-five years old male patient with a squamous cell
      carcinoma (SCC) originated from the right external ear four years ago. He was
      undergone surgical removal of the lesion with a combination of modified neck
      dissection and reconstruction with the use of pectoralis major flap. Furthermore,
      he had radiotherapy with 6000 rads of the right temporal region. Two months ago
      the patient showed an extended recurrence concerning the temporal muscle and
      bone, the lithoid bone, the masseter and the pterygoid muscles, the right part of
      the mandible, the parotid gland with the facial nerve, and the superior bulb of
      the internal jugular vein. He had a surgical removal of the lesion in extended
      healthy margins and functional and esthetic reconstruction of the defect with a
      combination of metal fixed prosthesis of the condyle and the right mandible and
      the use of myocutaneous trapezius flap. This is a case report of the
      reconstruction options we have nowadays to provide quality of life in cancer
      patients.

PMID- 16446898
TI  - Cholesteatoma of external auditory canal: a case report.
AB  - The authors present a case of cholesteatoma of external auditory canal (CEAC)
      with extensive invasion of mastoid; ossicle chain and tympanic membrane remained
      intact. The only symptom was chronic otorrhea. Diagnosis was based on clinical
      elements and CT scan was used to measure pathology and program surgery. Treatment
      was modified radical mastoidectomy associated with meatoplasty. Due to the
      insidious character of CEAC and the proximity with important structures of the
      external auditory canal, it must be always considered in differential diagnosis
      for lesions of external auditory canal. This case report intended to review
      clinical and surgical aspects of treatment of CEAC and present our approach in a
      case with severe lesions.

PMID- 16446899
TI  - Onset of subcutaneous emphysema and pneumomediastinum after tonsillectomy: a case
      report.
AB  - Several complications can be related to surgical approaches of head and neck
      regions. Among those, there are rare conditions such as pneumomediastinum,
      pneumothorax and subcutaneous cervical emphysema. This study reports a case of a
      patient that developed pneumomediastinum, pneumothorax and subcutaneous emphysema
      after undergoing tonsillectomy. In order to reduce these complications in
      surgical approaches such as tonsillectomy, care should be taken with intubation,
      use of oxygen mask for positive pressure ventilation during anesthesia recovery,
      aggressive surgical maneuvers and use of surgical instruments that may cause deep
      tonsillar injuries.

PMID- 16446900
TI  - Tympanic paragangliomas: case reports.
AB  - Glomus tumors, also called paragangliomas, originate from nonchromaffin cells.
      The tumor is typically vascular and grows from capillary and pre-capillary
      vessels in-between epithelial cells. It is worth mentioning that the most common
      symptoms are pulsating tinnitus and hearing loss. Imaging studies (CT and MRI)
      are necessary for diagnosis. This paper shows five patients seen at the Hospital
      between 1995 and 2001 presenting glomus tympanicum. Women were most commonly
      affected, and the age ranged from 48 to 60 years (mean age of 50 years). The most
      common complaints were pulsating tinnitus and hearing loss. All patients were
      treated surgically.

PMID- 16446901
TI  - Rhinolithiasis as cause of oronasal fistula.
AB  - Rhinolithiasis is a disease caused by deposition of organic and inorganic
      compounds in the nasal cavity, leading to unilateral nasal obstruction, fetid
      rhinorrhea, epistaxis, and it may cause complications. The authors present a case
      of rhinolithiasis with oronasal fistula and literature review.

PMID- 16446902
TI  - Intradermal melanocytic nevus of the external auditory canal.
AB  - Intradermal nevi are common benign pigmented skin tumors. Their occurrence within
      the external auditory canal is uncommon. The clinical and pathologic features of
      an intradermal nevus arising within the external auditory canal are presented,
      and the literature reviewed.

PMID- 16446903
TI  - Treacher Collins Syndrome with choanal atresia: a case report and review of
      disease features.
AB  - Treacher Collins Syndrome--or mandibulofacial dysostosis--is a rare condition
      that presents several craniofacial deformities of different levels. This is a
      congenital malformation involving the first and second branchial arches.
      Incidence is estimated to range between 1-40,000 to 1-70,000 of live births. The
      disorder is characterized by abnormalities of the auricular pinna, hypoplasia of
      facial bones, antimongoloid slanting palpebral fissures with coloboma of the
      lower eyelids and cleft palate. Treacher Collins Syndrome is rarely associated
      with choanal atresia. A multidisciplinary team, including craniofacial surgeon,
      ophthalmologist, speech therapist, dental surgeon and otorhinolaryngologist, is
      the most appropriate setting to manage these patients. This study reports a rare
      case of Treacher Collins Syndrome with choanal atresia, presenting literature
      review and multidisciplinary intervention.

PMID- 16446904
TI  - Pulsatile tinnitus: treatment with clonazepam and propranolol.
AB  - Pulsatile tinnitus synchronous with heartbeat is rare and normally has vascular
      origin: arterial (malformation, arterial anatomical variation) or venous
      (aberrant jugular bulb, glomus tumors, tympanic glomus tumor). Early etiology
      identification is essential for appropriate treatment to be established. Magnetic
      angioresonance makes the vascular identification possible and precise. We report
      a case of arterial anatomical variation in which the treatment was propranolol
      and clonazepam, showing tinnitus improvement.

PMID- 16446905
TI  - A specialty forged on its doubts.

PMID- 16446906
TI  - Neuropeptide immunofluorescence in human nasal mucosa: assessment of the
      technique for vasoactive intestinal peptide (VIP).
AB  - Neuropeptides are important neurotransmitters in nasal physiology and the
      increasing knowledge of their role in nasal diseases brings new therapeutic
      perspectives. The investigation of human nasal mucosa neuropeptides is based
      mostly on immunocytochemistry, a complex approach whose resulting factors may be
      variable. Aiming to make this kind of research available, an immunofluorescence
      approach for vasoactive intestinal peptide (VIP) in human nasal mucosa is
      proposed and evaluated. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD:
      Human inferior turbinate samples were obtained at time of nasal surgery from
      eight patients. The samples were fixed in Zamboni solution (4% phosphate-buffered
      paraformaldehyde and 0.4% picric acid), snap-frozen and stored at -70 degrees C.
      14 microm sections were then obtained. Immunofluorescence staining for VIP
      (Peninsula Laboratories) was performed and its images documented by conventional
      photography. The method's specificity, sensitivity and reproducibility of
      execution were evaluated. Additionally, the reproducibility of interpretation of
      results was evaluated through the comparison of staining scores (0 to 4)
      attributed to the images by six observers. RESULTS: The results showed the
      approach to be very specific and sensible, besides being reproducible in its
      execution. The interpretation of results may depend on the observer's accuracy in
      judging immunofluorescence images, but it showed uniformity. CONCLUSION: The
      proposed method was highly useful for research purposes in neuropeptides in human
      nasal mucosa.

PMID- 16446907
TI  - Luffa operculata effects on the epithelium of frog palate: histological features.
AB  - Luffa operculata is the botanical name of buchinha-do-norte or cabacinha, which
      is a medicinal plant widely used for the treatment of rhinitis and
      rhinosinusitis. In Europe and USA, it is available in homeopathic medicines. In
      Brazil, Luffa operculata dry fruit infusion is inhaled or instilled into the nose
      releasing profuse mucous secretion, thus relieving nasal symptoms. Nevertheless,
      this often may cause irritation, epistaxis or anosmia. STUDY DESIGN:
      Experimental. MATERIAL AND METHOD: The effects of Luffa operculata were evaluated
      in different concentration infusions, in isolated frog palate preparation,
      testing 46 palates after immersion. Four groups (n = 10) were tested with the
      infusion prepared with frog Ringer (isotonic): control; 60 mg/L; 600 mg/L; and
      1200 mg/L. An additional group was tested using the infusion with water (600 mg/L
      H2O, n = 6). Epithelial samples were harvested to be studied under light
      microscopy and electron transmission microscopy. RESULTS: In treated palates,
      light microscopy findings were dose-dependent standard toxic changes. Electron
      transmission microscopy showed enlargement of intercellular spaces and tight
      junctions disruption, pointing to ion-fluid transport abnormalities. CONCLUSIONS:
      Luffa operculata infusion in currently used doses can promote significant
      structural and ultrastructural changes in the epithelium of this ex vivo model of
      respiratory mucosa.

PMID- 16446908
TI  - Training the osteoplastic flap technique in dogs.
AB  - Access to frontal sinus using the osteoplastic flap technique is indicated in
      lesions that do not yield endonasal approach. This technique can be practiced
      with dogs, although delineation of sinusal perimeter in canines is not as easy as
      it is in humans. AIM: This study aims at presenting a method to access and
      delineate the frontal sinus of canines to reproduce the osteoplastic flap
      technique in man. STUDY DESIGN: Surgical technique in animal. MATERIAL AND
      METHOD: In adult dogs, two straight lines were drawn: one along the median line
      of the frontal region; and the other at 45 masculine from the pupil. At the
      intersection point, 1-1.5 cm forward and 1 cm backward was measured; from these
      points, an incomplete rectangle delineating the frontal sinusal perimeters was
      drawn. RESULTS: This procedure was performed 12 times during one year with
      participation of medical residents. Opening the animals' frontal sinuses was an
      easy procedure, and the osteoplastic technique to locate the sinus was performed
      without failures. CONCLUSION: The method of locating and delineating the frontal
      sinus of dogs was useful to show that the osteoplastic technique is realistically
      reproducible in men.

PMID- 16446909
TI  - Nasal endoscopy and localization of the bleeding source in epistaxis: last
      decade's revolution.
AB  - Epistaxis remains one of the most common otolaryngology emergencies. Despite
      considerable interest in the subject, there is still no consensus on the most
      appropriate primary therapeutic modality. AIM: The purpose of this study was to
      evaluate the bleeding source of acute or recurrent epistaxis in adults. STUDY
      DESIGN: Clinical prospective. MATERIAL AND METHOD: Thirty adults patients with
      acute or recurrent epistaxis were evaluated through the use of frontal light and
      endoscope for identification of the bleeding source in the nasal cavity. RESULTS:
      Use of the nasal endoscope allowed diagnosis of the bleeding site in all
      patients. CONCLUSION: A careful examination of the posterior nasal cavity allows
      identification of the bleeding source in most patients and should be a routine
      procedure.

PMID- 16446910
TI  - Acoustic rhinometry: anatomic correlation of the first two notches found in the
      nasal echogram.
AB  - The graphic obtained by acoustic rhinometry in Caucasian adult individuals with
      no nasal affections clearly shows two notches at the beginning of the nasal
      echogram. However, there are controversies in the literature concerning their
      anatomic correlation. AIM: The aim of this study was to obtain data that would
      contribute to the anatomic correlation of these two notches. STUDY DESIGN:
      Clinical prospective. MATERIAL AND METHOD: We analyzed the nasal echogram of 35
      volunteers in basal conditions, after decongestion and after obstruction of the
      nasal valve by using cotton impregnated with Vaseline. RESULTS: We identified
      statistically significant reduction and increase of the cross-sectional area only
      for the second notch after obstruction of the nasal valve and after decongestion,
      respectively. CONCLUSION: The analysis of the results suggested that the first
      notch of the nasal echogram refers to the nostril and the second notch refers to
      the nasal valve as a whole.

PMID- 16446911
TI  - Breathing mode influence in craniofacial development.
AB  - AIM: The aim of this study was to evaluate the differences in facial proportions
      of nose and mouth breathing children using cephalometric analysis. STUDY DESIGN:
      Transversal cohort. MATERIAL AND METHOD: Sixty cephalometric radiographs from
      pediatric patients aged 6 to 10 years were used. After otorhinolaryngological
      evaluation, patients were divided into two groups: Group I, with mouth breathing
      children and group II, with nose breathers. Standard lateral cephalometric
      radiographs were obtained to evaluate facial proportions using the following
      measures: SN.GoGn, ArGo.GoMe, N-Me, N-ANS, ANS-Me and S-Go; and the following
      indexes: PFH-AFH ratio: S-Go/N-Me; LFH-AFH ratio: ANS-Me/N-Me and UFH-LFH ratio:
      N-ANS/ANS-Me. RESULTS: It was observed that the measurements for the inclination
      of the mandibular plane (SN.GoGn) in mouth breathing children were statistically
      higher than those in nasal breathing children. The posterior facial height was
      statistically smaller than the anterior one in mouth breathing children (PFH-AFH
      ratio). Thus, the upper anterior facial height was statistically smaller than the
      lower facial height (UFH-LFH ratio). CONCLUSION: We concluded that mouth
      breathing children tend to have higher mandibular inclination and more vertical
      growth. These findings support the influence of the breathing mode in
      craniofacial development.

PMID- 16446912
TI  - Description of microscopic lesions of vestibular folds of autopsied adults and
      their relationship with cause of death and underlying disease.
AB  - The increase in invasive methods currently applied to diagnosis airway upper
      tract infection leads to a possible increase in vestibular folds (VF) lesions.
      Besides, VF importance in the prevention of the organism against infection
      pathogens had been stressed and few studies had addressed the microscopic lesions
      of the VF in autopsied patients because there is no routine VF examination in the
      postmortem exam. AIM: The aim of this study is morphological microscopic analyses
      of the VF from autopsied patients and its correlation with basic disease and
      cause of death. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: We studied
      82 larynges collected during the autopsy exam and performed the Hematoxylin 
      eosin method for morphological analyses. RESULTS: From the 82 vestibular folds
      analyzed we observe that 42 (51%) showed an inflammatory reaction. In fifteen
      (18.3%) vestibular folds we found lymphoid follicular hyperplasia, in eleven
      (13.4%) diffuse inflammatory infiltrate and in sixteen (19.5%) acute inflammatory
      reactions. Circulatory diseases were the most frequently underlying diseases
      found, 31 (37.8%) and from these 20 (67.8%) presented associated vestibular folds
      inflammatory reaction. The infection diseases were the most frequently cause of
      death among the patients with inflammatory reaction of the VF. CONCLUSION:
      Besides the anatomic function, VF seem to have a immunological function
      preventing lower airway infections. Our study demonstrated inflammatory PV
      reactions in patients with infections diseases as cause of death; this finding
      could be a consequence of the sepsis that leads the patient to death or a
      different way used by the organism to prevent infection.

PMID- 16446913
TI  - Role of rapid antigen detection test for the diagnosis of group A beta-hemolytic
      streptococcus in patients with pharyngotonsillitis.
AB  - Group A beta-hemolytic streptococcus (GAS) is an important pharyngotonsillitis
      etiologic agent. Correct etiologic diagnosis and early treatment prevent
      suppurative and non-suppurative complications of streptococcal
      pharyngotonsillitis; however, clinical diagnosis is not reliable. Within this
      context, rapid detection methods of GAS antigen are useful to diagnose this
      agent. AIM: The objective of the present study was to determine sensitivity and
      specificity of rapid GAS antigen detection tests used in Brazil. STUDY DESIGN:
      Clinical prospective. METHOD: Eighty-one patients with clinical diagnosis of
      acute pharyngotonsillitis seen at the otorhinolaryngology emergency department of
      the University Hospital, FMUSP, between May 2001 and April 2002 were submitted to
      two simultaneous collections of oropharyngeal material using swabs. The rapid GAS
      antigen detection test was compared to culture on blood agar, the gold standard
      for the diagnosis of this etiologic agent. RESULTS: Among the 81 patients
      studied, the rapid test was positive in 56% and negative in 44%. GAS growth in
      culture was observed in 40.7% of the patients. Sensitivity and specificity of the
      rapid test were, respectively, 93.9% and 68.7%, and the negative and positive
      predictive values were 94.2 and 67.4%, respectively. CONCLUSIONS: We concluded
      that high sensitivity of the test allows its use in the identification of
      patients with GAS. Rapid streptococcal antigen detection tests have been shown to
      be an important adjuvant tool in the etiologic diagnosis of pharyngotonsillitis.

PMID- 16446914
TI  - Vocal impact on quality of life of elderly female subjects.
AB  - Although there are several investigations focusing the physiology and anatomy of
      voice and the senior's larynx, little has been produced to support the knowledge
      of the impact of vocal conditions on quality of life of this portion of the
      population. AIM: To verify the impact of voice on quality of the life of elderly
      women, using the questionnaires Short-Form Health Survey--SF36 and Voice Handicap
      Index (VHI). STUDY DESIGN: Prospective transversal cohort study. METHOD AND
      MATERIAL: Fifty senior women participated in this research, with ages between 60
      and 87 years and mean age of 70.8 years old, randomly recruited. The participants
      of the study were submitted to two questionnaires: SF36 and VHI. The answers of
      both questionnaires were compared by Kruskall-Wallis test, verifying if there
      were significant differences among the variables. The test of Spearman was used
      to evaluate if there was correlation among the results of the variables of VHI
      and the results obtained in the parameter of SF36 for life quality. RESULTS: We
      obtained values considered statistically significant in the correlations among
      physical domain of VHI and physical operation, physical pain and physical role in
      life of SF36. CONCLUSION: There was a significant and positive correlation among
      the results obtained in the parameters physical operation, vitality, general
      health, mental health, corporal pain and physical role in life of SF36. There
      were statistically significant and negative correlations among the total results
      obtained in SF36 and VHI.

PMID- 16446915
TI  - Correlation between TNM classification and malignancy histological feature of
      oral squamous cell carcinoma.
AB  - Histological staging of deep invasive margin of oral squamous cell carcinoma has
      a significant influence on survival of patients since the tumor cells are more
      poorly differentiated in this area and have high prognostic value. AIM: The
      purpose of the present study is to correlate TNM clinical classification with
      histopathologic characteristics (degree of keratinization, nuclear pleomorphism,
      invasion pattern and lymphoplasmocytic infiltrate) and histologic malignancy
      scores in 38 cases of oral epidermoid carcinoma in the lesion's deepest areas.
      STUDY FORM: Retrospective clinical study. MATERIAL AND METHOD: This is a
      retrospective study based on histological review of 38 cases of oral squamous
      cell carcinoma selected from the medical files of Hospital Dr. Luis Antonio,
      Natal--Rio Grande do Norte, Brazil. TNM clinical classification data were
      obtained from the analysis of the medical records. Two pathologists performed
      histological malignancy staging on routine 3 microm-thick sections of invasive
      tumor areas stained with hematoxylin and eosin. For statistical analysis,
      parametric (ANOVA) and non-parametric tests (Tukey; Pearson; Chi2) were employed.
      RESULTS: We found significant correlation between TNM clinical staging and
      malignancy mean score (p= 0.001) and histopathologic parameters, such as nuclear
      pleomorphism (p= 0.016) and degree of keratinization (p= 0.025). Furthermore,
      there were also statistically significant correlations between lymphocytic
      infiltration (p= 0.016) and nuclear pleomorphism (p= 0.004) with TNM
      classification when grouped in two series: TNM I/II and III/IV. CONCLUSION: TNM
      classification, as well as malignancy mean score, had statistically significant
      correlation with degree of keratinization, nuclear pleomorphism and lymphocytic
      infiltration. These highly significant results indicated that histologically
      invasive areas may be primarily responsible for the clinical behavior of the
      tumor, and this may be important for the therapy of choice for oral squamous cell
      carcinoma.

PMID- 16446916
TI  - Growth of cholesteatoma by implantation of epithelial tissue along the femoral
      bone of rats.
AB  - Cholesteatoma is a well-known infection resembling a pearl. Its histological
      aspect is of an epidermal cyst formation characterized by epidermal-keratinized
      tissue in the middle ear and mastoid that can migrate and erode to adjacent
      structures. AIM: To verify epidermal cyst (cholesteatoma) growth through
      implantation of auricular skin of a mouse next to its femoral bone. STUDY DESIGN:
      Experimental. MATERIAL AND METHOD: Ten healthy rats between two and five months
      of age and of both sexes underwent implantation of auricular skin on the femoral
      bone during a three-month period. Paraffin-embedded sections were obtained from
      the sample and stained with hematoxylin and eosin for pathology investigation.
      RESULTS: Macroscopic view: round soft yellowish granulation tissue. Microscopic
      view: keratinizing stratified squamous epithelium cystic formation. The cyst
      presented innermost corneal layer, resulted from keratinized skin, followed by
      granulated and squamous layers, and outermost basal layer. CONCLUSIONS: Growth of
      epidermal cyst (cholesteatoma) may start from a transplanted epithelial tissue
      next to the femoral bone of rats.

PMID- 16446917
TI  - Auditory screening in the elderly: comparison between self-report and audiometry.
AB  - Despite its high prevalence in the aged, hearing loss has been poorly
      investigated. Audiometry is the gold standard for evaluation of hearing loss, but
      large-scale use of the procedure involves operational difficulties. Thus, self
      report may be an alternative. AIM: To determine if a single global question is
      valid for use in epidemiologic research. STUDY DESIGN: Systematic review.
      MATERIAL AND METHOD: A search of the medical literature from 1990 to 2004 was
      performed using MEDLINE and LILACS. The references of the articles identified in
      the electronic search were also reviewed. STUDY SELECTION AND DATA EXTRACTION:
      The articles that compared the results obtained with self-report to a single
      global question with those obtained by pure tone audiometry were selected. Data
      about the prevalence of hearing loss, and sensitivity, specificity and predictive
      values were extracted. DATA SYNTHESIS: Ten longitudinal studies were included. A
      single global question seems to be an acceptable indicator of hearing loss,
      sensitive and reasonably specific, mainly if the hearing loss is identified as
      the tone average that includes frequencies up to 2 or 4 kHz, at 40 dBHL level, in
      the best ear. CONCLUSION: A single global question shows good performance in
      identifying older persons with hearing loss and can be recommended for an
      epidemiologic study if audiometric measurements cannot be performed.

PMID- 16446918
TI  - Cognitive P300 potential in subjects with Diabetes Mellitus.
AB  - Diabetes Mellitus may lead to alterations in the eyes, kidneys, cranial nerves,
      peripheral nerves, ears etc. The cognitive function also seems to be compromised
      in subjects presented with Diabetes Mellitus, since the cortical and subcortical
      structures responsible for this function are hindered in some insulin-dependent
      patients. The cognitive potential P300 has been used as an objective procedure to
      assess cerebral cognitive functions. AIM: To analyze the sensitivity of P300
      cognitive potential for the detection of alterations on the auditory cortex
      secondary to Diabetes Mellitus. STUDY DESIGN: transversal cohort. MATERIAL AND
      METHOD: Sixteen diabetic subjects of both genders aged 7 to 71 years, and
      seventeen non-diabetic individuals at the same age range participated in this
      study. The evaluation procedures were pure tone audiometry (PTA) and P300
      cognitive potential. Glycemia of the group presented with Diabetes was assessed
      prior to applying P300. RESULTS: No statistically significant difference was
      shown for PTA results. A statically significant difference was observed between
      groups when analyzing the latency of P300 component measured in Fz. There was a
      correlation between glycemia and latency and amplitude of P300. CONCLUSION: The
      investigation of the cognitive potential of P300 is an important procedure for
      prevention and early diagnosis of neurological changes in individuals presented
      with Diabetes Mellitus.

PMID- 16446919
TI  - Diabetes mellitus as etiological factor of hearing loss.
AB  - Patients with diabetes mellitus often show symptoms such as dizziness, tinnitus,
      and hearing impairment. In general, hearing loss is sensorineural, which is
      sometimes confused with presbycusis, mainly because it develops in patients older
      than 40 years of age. Angiopathy and neuropathy caused by diabetes mellitus have
      been considered important factors for the vestibular-cochlear disorders found in
      these patients. However, there is controversy regarding the etiopathogenesis of
      hearing loss, as some researchers support that it develops due to neuropathy,
      others say it is due to angiopathy, or even a combination of both. Yet, some
      researchers believe diabetes mellitus and hearing loss are part of a genetic
      syndrome. We have conducted an extensive bibliographic review to determine
      whether there is cause-effect relationship between diabetes mellitus and hearing
      loss. We were able to verify that, despite the large number of studies performed,
      there is still a great deal of controversy, and new approaches are being studied,
      for example in the field of genetics, which shows that new paths can be followed
      to reach a conclusion on this issue.

PMID- 16446920
TI  - Molecular genetics of non-syndromic deafness.
AB  - One in every 1,000 newborn suffers from congenital hearing impairment. More than
      60% of the congenital cases are caused by genetic factors. In most cases, hearing
      loss is a multifactorial disorder caused by both genetic and environmental
      factors. Molecular genetics of deafness has experienced remarkable progress in
      the last decade. Genes responsible for hereditary hearing impairment are being
      mapped and cloned progressively. This review focuses on non-syndromic hearing
      loss, since the gene involved in this type of hearing loss have only recently
      begun to be identified.

PMID- 16446921
TI  - Apocrine carcinoma in the parotid gland and in the submandibular region.
AB  - The objectives of this paper are to report a case of apocrine carcinoma and the
      discussion of aspects related to its diagnosis, treatment, and prognosis.
      Carcinomas with apocrine differentiation not related to extramammary Paget's
      disease, ductal breast carcinoma, Moll's glands adenocarcinoma and ceruminous
      glands carcinoma are very uncommon tumors. We report a case of a 51-year-old
      black woman who developed apocrine carcinoma lesions in the head and neck region.
      Two lesions involved her left parotid gland (first tumor and local recurrence),
      and other involved her submandibular skin. The microscopic aspects were as
      follows: infiltrative glandular epithelial neoplasm with moderate cellular and
      nuclear pleomorphism; neoplasic cells with polygonal or circular shape, large
      nuclei and eosinophilic and granular cytoplasm. The apical decapitation secretion
      was viewed in a large number of intra-cystic tumor cells. Moreover, we found
      areas with comedo-necrosis or PAS positive staining (with or without diastase).
      Based on cutaneous apocrine carcinoma compatibility of the microscopic aspects,
      we concluded that the tumor in the submandibular skin was probably the primary
      neoplasm. The patient was treated by surgical excisions, and no evidence of
      recurrent or metastatic disease has been seen after a follow-up period of 12
      months.

PMID- 16446922
TI  - Rare osteodysplasia of the temporal bone.
AB  - Temporal bone osteodysplasia can produce many different symptoms, such as
      involvement restricted to the temporal bone or impairment of other bones. We
      consider, in this study two entities that are rare osteodysplasia cases, which
      are osteopetrosis and Camurati-Engelmann disease, the latter being extremely
      rare. We present two cases of benign form of osteopetrosis (Albers-Schulenburg's
      disease), a patient of 11 years old and another one of 48 years old, both male,
      and a patient of 28 years old, female, with Camurati-Engelmann's disease. The
      facial palsy was a manifestation in two of the patients. We discuss some aspects
      about the clinical manifestations, radiological findings, as well as differential
      diagnostic and therapy in view of the complications of the diseases.

PMID- 16446923
TI  - Foreign body aspiration through tracheotomy: a case report.
AB  - A 70 year-old man, with a 7-year tracheotomy because of a laryngeal tumor, had an
      accident during daily canulla cleansing procedure, aspirating a piece of the
      cleaning brush. Chest radiograph showed metallic foreign body at the right
      inferior bronchus. Rigid bronchoscopy was performed under general anesthesia,
      with no resistance in passing the tube through the glottis. The foreign body was
      easily removed and the patient had no complications. After leaving the hospital,
      the patient was sent to the ENT service where he used to be followed up.

PMID- 16446924
TI  - Osteosarcoma of mandible initially resembling lesion of dental periapex: a case
      report.
AB  - Osteosarcoma is a malignant mesenchymal tumor whose cancerous cells produce
      osteoid matrix. It is the most common primary malignant bone tumor, accounting
      for approximately 20% of the sarcomas, but only 5% of the osteosarcomas occur in
      the jaws. They present various clinical and histological aspects, as well as
      variable disease progression and outcome. This article shows a case report of a
      20-year-old woman who presented swelling near the mandibular left premolar. After
      clinical diagnosis of lesion of the dental periapex, the patient initially
      underwent endodontic treatment of the tooth involved. Thereafter, in a period of
      eleven days, a significant increase of the lesion could be observed, resulting in
      visible facial asymmetry. The occlusal radiographic view showed an area of bone
      destruction and abnormal bone formation in the region. The external cortical
      portion showed clear radiopacity resembling sunrays, suggesting the diagnosis of
      osteosarcoma. The treatment comprised partial mandibulectomy and reconstruction
      of the area, using bone of the rib and skin graft from the buttock for the oral
      mucosa involved. Eight months after surgery, there was local recurrence of the
      lesion and the patient died approximately one year after relapse.

PMID- 16446925
TI  - Congenital nasal pyriform aperture stenosis.
AB  - The congenital stenosis of pyriform aperture is an unusual cause of neonatal
      nasal obstruction. It is due to bony overgrowth of the nasal lateral process of
      the maxilla. Initially this narrowest part of nasal airway was considered an
      isolated deformity; subsequently the congenital Stenosis of pyriform aperture was
      thought to represent a microform of holoprosencephaly. In this report a male
      neonate had respiratory distress, cyclic cyanosis and apnea after delivery. The
      patient underwent surgical correction of pyriform stenosis by sublabial access.
      In the follow up, the patient had good evolution. The report of this deformity
      shows an important cause of neonatal nasal obstruction and its differential
      diagnosis with bilateral choanal atresia. Congenital stenosis of nasal pyriform
      aperture can be surgically corrected when necessary.

PMID- 16446926
TI  - Rhinosinusitis in a patient with Behcet's syndrome.
AB  - The condition known as Behcet's syndrome was first described by H. Behcet, a
      dermatologist from Turkey. Its major component is recurrent aphthous-like lesions
      of the oral mucosa. Some groups of people such as the Japanese are more prone to
      develop the condition. Behcet's syndrome is relatively rare in the American
      continent. In addition to oral lesions, these patients may develop recurrent
      genital ulcerations, uveitis, and pustular vasculitis of the skin, synovitis, and
      meningoencephalitis. The diagnosis is based on occurrence of internationally
      proposed major or/and minor criteria and on their combinations. Treatment is
      challenging and must be tailored to each patient according to the pattern of
      organ involvement, often requiring use of combined therapies. The clinical
      picture of the patients in this study confirmed Behcet's Syndrome diagnosis.
      Vasculitis was evidenced by the absence of bleeding during the handling of some
      very bloody potential areas. In the present case, not only the triggering but
      also the complications of rhinosinusitis (periorbitary abscess) were attributed
      to Behcet's vasculitis, specially the effects on bloody perfusion and draining.
      Rhinosinusitis is a potential symptom of Behcet's Syndrome. Physicians must pay
      attention to it in order to achieve satisfactory outcomes.

PMID- 16446927
TI  - [The problem of waiting lines for otorhinolaryngology surgeries in public
      services].

PMID- 16446928
TI  - [Amifostine otoprotection to cisplatin ototoxicity: a guinea pig study using
      otoacoustic emission distortion products (DPOEA) and scanning electron
      microscopy].
AB  - Cisplatin is an antineoplastic drug for cancer treatment in children and adults.
      The side effects of cisplatin ototoxicity are significant: irreversible bilateral
      hearing damage to high frequencies (4 kHz - 8 kHz). Reports recognize some drugs
      that are associated with cisplatin to obtain an otoprotector effect. The
      ototoxicity mechanisms of cisplatin are related to injury of hair cell oxidation
      mechanism, especially of outer hair cells. AIM: Using otoacoustic emissions
      distortion products (DPOEA) and scanning electron microscopy we intended to
      verify the action of amifostine, a radioprotective drug that has well known
      antioxidant characteristics and otoprotector effects to cisplatin injury. STUDY
      DESIGN: Experimental. MATERIAL AND METHODS: We used an experimental guinea pig
      model. The study was performed as follows: group 1: 6 animals, 12 ears, cisplatin
      8.0 mg/Kg/day (IP), 3 days. Group 2: 6 animals, 12 ears, amifostine 100 mg/Kg/day
      (IP) and after 90 minutes, cisplatin 8.0 mg/Kg/day (IP), 3 days and group 3: 3
      animals, 6 ears, amifostine 100 mg/Kg/day (IP), 3 days. RESULTS: DPOEA were
      present before and after treatment in groups 2 and 3. The normal cilium
      architecture of outer hair cells was supported in all cochlear turns in groups 2
      and 3. We concluded that amifostine has a potential otoprotector effect against
      cisplatin ototoxicity and could be used in clinical trials.

PMID- 16446929
TI  - [Evaluation of tympanometric alterations in patients subject to general
      anesthesia with nitrous oxide].
AB  - The nitrous oxide is an inhaling gas that can increase intratympanic pressure
      during the anesthetic act and cause negative pressure after it is discontinued,
      mainly in patients with Eustachian tube dysfunction. These pressure variations
      may come up with clinical implications such as tympanic membrane rupture,
      ossicular system disarticulation, haemotympanum, barotraumas, prosthesis
      displacement stapaedotomy and tympanic graft lateralization after tympanoplasty,
      in addition to serous fluid entrance into the middle ear during the negative
      pressure phase. AIM: To evaluate the nitrous oxide influence on the middle ear
      pressure in a population without tube malfunction performing pre and
      postoperative tympanometry. STUDY DESIGN: Transversal cohort. MATERIAL AND
      METHOD: A prospective study was carried out with Universitario Clementino Fraga
      Filho Hospital- UFRJ intern patients, subject to general anesthesia with the use
      of 50% nitrous oxide from April to June 2003. It was also evaluated whether the
      duration of surgery, associated anesthetics, presence of allergic rhinitis and
      nasal septal deviation could contribute to the appearing of intratympanic
      pressure alteration. RESULTS: The sample is made up of 50 patients, in almost
      half of them (48%), postoperative tympanometry alterations (type C curve) were
      found, when comparing to the preoperative tympanometric control (type A curve).
      Neither sex nor age interfered in the appearing of tympanometry alterations
      during the post operative as well as the surgery timing. The anesthetic type
      volatile associate, nasal septal deviation and allergic rhinitis were not able to
      influence during the postoperative middle ear pressure. CONCLUSION: The nitrous
      oxide modifies intratympanic pressure during the anesthetic act as well as after
      it was discontinued.

PMID- 16446930
TI  - [Anatomical references in auditory brainstem implant surgery].
AB  - The auditory brainstem implant (ABI) is an option for deaf patients who do not
      have the whole of their auditory pathways preserved. The surgery, because of its
      anatomical and functional complexity, requires specific training of the surgeon
      in an anatomy lab. AIM: To study the surgical anatomy of the surgery for auditory
      brainstem implant. STUDY DESIGN: Anatomic study. MATERIAL AND METHOD: In this
      exercise we dissected a fresh cadaver prepared with a dye solution injected into
      the arteries and intra-cranial veins. The location for the insertion of the
      electrode for the ABI has been studied through the translabyrinthine access.
      RESULTS: The surgical technique used for implanting the electrode of the
      brainstem is similar to that used in the removal of the schwannoma vestibular.
      The cochlear nucleus complex, composed of the ventral and dorsal cochlear nuclei
      is the location for placing the electrode. The ventral cochlear nucleus is the
      principal nucleus for transmission of neural impulses from the VIII par and form
      the main ascendant route of the cochlear nerve. Neither the ventral nor the
      dorsal nuclei are visible during surgery and their location depends on the
      identification of adjacent anatomical structures. CONCLUSION: The region for the
      implantation of the electrode in the auditory brainstem implant presents
      anatomical references that allow its easy identification during surgery.

PMID- 16446931
TI  - [Distribution of neurotological findings in patients with cochleovestibular
      dysfunction].
AB  - The relationship between spatial body positioning and environment comes from
      perfect corporal balance. The three most important systems responsible for this
      relationship are: the optic system (sight), the proprioceptive system, and the
      labyrinthine system. STUDY DESIGN: Retrospective clinical. A retrospective study
      conducted on 3,701 patients of a private otolaryngologic clinic, in Jundiai - Sao
      Paulo - Brazil, who underwent vestibular and cochlear labyrinthine function
      testing, from 1979 to 2004. AIM: To determinate the syndromic distribution
      occurred at that population and to correlate its relationship with sex, age,
      symptomatology, as well as otological, clinical and electronystagmographic
      findings and which were the most frequent medical specialties who asked for this
      investigation. RESULTS: There was found in the studied population a major
      prevalence on females (1.75:1). Seventy-nine percent of the patients were from 20
      to 59 years old, therefore including people in labor age, with a major prevalence
      of peripheral syndromes, but there was no a preferential age or sex group among
      the different syndromes. This study also demonstrated that some otoneurological
      symptoms were common to all kind of otoneurological syndromes, in opposition to
      the data found in the world literature. Tinnitus, hearing loss, nausea and vomit
      as well as harmonic alterations on clinical examination were found with more
      frequency on peripheral syndrome and no harmonic on central syndromes, according
      to the reviewed literature. CONCLUSIONS: The study conclusions were able to show
      that the majority of the patients started their investigation with either
      otolaryngologists or neurologists and 36% of the patients had peripheral syndrome
      with almost 25% that had normal evaluation.

PMID- 16446932
TI  - [Balance in the elderly].
AB  - Throughout years, the human organism goes through natural aging, having
      functional and structural changes. The part which is responsible for the corporal
      balance system also suffers from the aging process, creating great impact for the
      elderly. AIM: Thus, the present paper aims to study the vestibular function of
      old people suffering from dizziness, tinnitus and hearing impairment. STUDY
      DESIGN: Transversal cohort. MATERIAL AND METHOD: 80 elderly individuals from two
      different groups were evaluated: group A - composed of 38 women and 2 men who
      belonged to an elderly group from Santa Maria, RS; and group B - composed of 35
      women and 5 men with complaints of balance disorders. RESULTS: Both groups were
      undergone anamnesis (calling attention to aspects concerning the dizziness,
      tinnitus and the hearing impairment), and the vestibular function evaluation (by
      using the computerized system of vecto-electronystagmography SCV 5.0). The
      results displayed a statistical significant difference between both groups,
      concerning the complaints of dizziness and tinnitus, straightforward in group B.
      In the hypothetical diagnosis lead by the computerized examination, it was found
      that most individuals had presented normal diagnosis; however, it was found the
      predominance of vestibular disorders in the elderly such as Deficit Peripheral
      Vestibular Syndrome and Irritative Peripheral Vestibular Syndrome. CONCLUSION: It
      was concluded that the vestibular disorders, according to the vecto
      electronystagmography, and to the complaints of dizziness, tinnitus and hearing
      impairment, are numerically similar in both studied groups.

PMID- 16446933
TI  - [Evaluation of patients with dizziness and normal electronystagmography using
      stabilometry].
AB  - The causes of dizziness are difficult to be diagnosed. At present we have a
      variety of tests and exams but none of them can adequately evaluate the
      vestibular function. The most commonly used tests are electronystagmography and
      posturography. AIM: The objective of this study was to analyze the results of
      stabilometry in patients with complaints of dizziness who had normal results in
      electronystagmography and to compare them with a control group. STUDY DESIGN: The
      study was prospective, sectional transverse. MATERIAL AND METHOD: It was
      conducted at the ENT department of the University Hospital in Rio de Janeiro's
      Federal University. Twenty-two patients (fifteen women and seven men) were
      evaluated with ages, on average, of 47.6+/-9. The control group was made up of
      twenty-five healthy individuals (eighteen women and seven men) with ages, on
      average 46.8+/-7. RESULTS: In all analyzed parameters, there were statistically
      significant differences between the groups. Comparing the results with eyes
      closed and opened, the antero-posterior medium velocity, in control group, was
      the only statistically significant result. CONCLUSION: We concluded that the
      group of patients had results statistically significant in relation to the
      control group in all the analyzed parameters, showing that the group of patients
      with complaints of dizziness had more instability in standing position than the
      group of healthy individuals.

PMID- 16446934
TI  - [Proposal of measurement of vertical larynx position at rest].
AB  - AIM: The purpose of this research is to propose a procedure to measure the
      vertical larynx position in the neck at rest, of young adults without vocal
      complaint. STUDY DESIGN: Transversal cohort study. MATERIAL AND METHOD: A number
      of 68 subjects, aged between 18 to 44 years, 33 female and 35 male, participated
      in this study. The referential points used for this research were the right and
      left jaw angle (RJA and LJA), the centre of the cricoid arch cartilage (CC) and
      the centre of the sternal furculum (SF). In order to obtain the measures, the
      subjects were asked to be sitting still with their heads stretched up to the
      highest possible position. The devices used were a drawing compass and a 20
      centimeter ruler. RESULTS: The measurement procedure demonstrated to be easily
      executed and it didn't show any discomfort to the participants. There was no
      statistically significant difference between sexes related to the vertical larynx
      position in the neck; however the women presented higher larynx position than
      men. The vertical larynx position was easily obtained and it seems to be a very
      interesting parameter to intra-subject clinical follow-up.

PMID- 16446935
TI  - [Vocal fold superficial layer of lamina propria histology after the position of
      mucosa pediculated flap: canine experimental study].
AB  - Many techniques were applied to treat patients with sulcus vocalis and scarred
      vocal folds. Their results were not good enough. In the Technique of Vocal Fold
      Pediculated Mucosa Flap, an anterior pediculated flap of vocal fold is positioned
      on the superficial layer of the lamina propria, below the free margin. AIM: To
      describe histological postoperative findings on the superficial layer of lamina
      propria during the application of the technique Vocal Fold Pediculated Mucosa
      Flap. The following parameters were compared between tested and control groups:
      total, type I and type III collagen and number of cellular nucleus. STUDY DESIGN:
      experimental. MATERIAL AND METHOD: Fifteen dogs were used. One vocal fold was
      submitted to the intervention and the other was left as control. Each group of
      three dogs was sacrificed on 10, 30, 90, 180 and 360 days after the experimental
      surgery. Hematoxylin and eosin (H.E.) and Syrius Red were the staining techniques
      used. RESULTS: Type I and total collagen suggested increased results in the
      tested group on postoperative days 90 and 180, nevertheless there was statistical
      significance only on postoperative day 180 (p<0.05). Type III collagen group area
      was less significant than the control group on postoperative day 180 (p<0.05).
      The number of cellular nucleus was increased on the 10th postoperative day, but
      decreased after the 30th day. DISCUSSION: The findings about total and type I
      collagen and the amount of cellular nucleus on the superficial layer of lamina
      propria were similar to laryngeal postoperative studies in dogs. More complex
      studies would contribute with new data about the present subject.

PMID- 16446936
TI  - [Identification of the external branch of the superior laryngeal nerve during
      minimally invasive video-assisted thyroidectomy].
AB  - The minimally invasive video-assisted thyroidectomy (MIVAT) without gas infusion
      is considered safe and has advantages in terms of cosmetic results compared to
      the conventional approach. AIM: to present our findings regarding the
      identification of the external branch of the superior laryngeal nerve (EBSLN)
      during MIVAT. STUDY DESIGN: Transversal cohort study. MATERIAL AND METHOD: twelve
      patients underwent hemithyroidectomy for thyroid nodular disease through MIVAT
      method. The upper pedicle of the thyroid was dissected under the magnified view
      at 0-degree five-millimeter endoscope in order to achieve the identification of
      EBSLN in all cases. RESULTS: We identified 10 (83.3%) EBSLN out of 12 cases. The
      nerve ran medially to the branches of the superior thyroid artery in 8 cases
      (80%) and crossed anteriorly in 2 (20%). CONCLUSIONS: We identified the EBSLN in
      83.3% of the cases, whose course was medial to the branches of the superior
      thyroid artery in 80% and crossing anteriorly in 20%. The ligation of the upper
      pedicle of the thyroid can be performed under direct view of the EBSLN.

PMID- 16446937
TI  - [Treatment laryngomalacia: experience with 22 cases].
AB  - Laryngomalacia is the most frequent cause of stridor in childhood, and in most of
      the cases, spontaneous resolution occurs by the age of 2 years. Approximately 10%
      of the cases (severe laryngomalacia) require surgery. This condition is of
      unknown etiology and its diagnosis is made by fiberoptic laryngoscopy, which
      shows shortening of the aryepiglottic folds, and/or redundant arytenoid mucosa,
      and/or anterior-posterior epiglottic prolapse. AIM: Our objective was to verify
      the main clinical and anatomical affections and to highlight the clinical
      parameters for clinical follow-up and surgical indication in patients with
      laryngomalacia. STUDY DESIGN: Transversal cohort study. MATERIAL AND METHOD:
      Twenty-two children diagnosed with laryngomalacia in the Pediatric
      Otorhinolaryngology of UNIFESP-EPM, from January 2001 to December 2003, whose
      clinical and surgical follow-up were performed by the same examiner, were
      enrolled in this study. RESULTS: Out of twenty-two evaluated children, 2 (9.1%)
      presented with severe laryngomalacia and pectus excavatum (funnel chest). At
      polysomnography, no child presented any significant respiratory event during
      sleeping. Those two children with severe laryngomalacia were submitted to
      supraglottoplasty with resection of the aryepiglottic folds. CONCLUSION: We
      concluded that stridor and shortening of the aryepiglottic folds are preponderant
      in children with laryngomalacia. The polysomnographic exam did not prove to be a
      good parameter for clinical follow-up, neither for surgical indication. The most
      important parameters were pectus excavatum and failure to thrive.
      Supraglottoplasty is effective with low rate of morbidity.

PMID- 16446938
TI  - [Epidemiologic profile of salivary gland neoplasms: analysis of 245 cases].
AB  - AIM: The aim of the present study is to establish the relative frequency and
      distribution of benign and malignant epithelial neoplasms of salivary glands in
      the Pathology and Cytology Laboratory, STUDY DESIGN: Historic cohort. MATERIAL
      AND METHOD: in the state of Sergipe, during the period 1980-1999. The neoplasms
      were individualized by gender, age, race of the patients, anatomic localization
      of the lesions and histopathological diagnosis. RESULTS: Out of 162,312
      registered cases, 245 were salivary gland epithelial neoplasms and 187 (76.33%)
      were benign and 58 (23.67%) were malignant. Pleomorphic adenoma was the most
      frequent benign neoplasm (89.94%) and adenoid cystic carcinoma represented the
      most prevalent malignant neoplasm (22.41%). The benign neoplasms occurred mainly
      between the second and third decades of life and showed preference for female,
      while malignant neoplasms were diagnosed between the sixth and seventh decades of
      life and in women. CONCLUSION: The data demonstrate that epidemiology profile of
      studied neoplasms corroborated the majority researched literature.

PMID- 16446939
TI  - [Lymphoma's manifestations in Sjogren's syndrome: is there a relation?].
AB  - Sjogren's Syndrome (SS) is considered a multisystemic chronic disorder, which is
      characterized by a lymphocytic infiltration of exocrine glands and autoantibodies
      production. AIM: Several studies have demonstrated increased incidence of
      Lymphoma in SS patients. Our study tries to determine this relation. STUDY
      DESIGN: Transversal cohort. MATERIAL AND METHOD: Patients with Sicca's Syndrome
      from the Stomathology service, Santa Casa de Misericordia Hospital, in Sao Paulo,
      ENT Department, from July 1999 to April 2002. RESULTS: Out of 39 patients, 24
      were diagnose as SS. Ages ranged from 19 to 83 years old, with predominance of
      women (69.7%). Time between the first symptoms and SS diagnosis were variable,
      ranging within 3.77 years. None of the analyzed patients developed lymphoma.
      CONCLUSION: Both SS early diagnosis and the increased risk of lymphoma's
      development in those patients are important, reason why long-term follow-up is
      essential. We observed that our findings were different from those in the
      literature. We did not detect any cases of lymphoma in our patients.

PMID- 16446940
TI  - [Evaluation of sialometry and minor salivary gland biopsy in classification of
      Sjogren's Syndrome patients].
AB  - Sjogren's Syndrome is an autoimmune disease of the exocrine glands, mainly
      salivary and lachrymal glands. There is no gold standard test for diagnosis. AIM:
      evaluation of the importance of minor salivary gland biopsy and sialometry,
      isolated or associated, as methods for classification of Sjogren's Syndrome.
      STUDY DESIGN: Transversal cohort. PATIENTS AND METHOD: Seventy-two patients that
      reported dry mouth from January 1997 to September 2003 were investigated and
      classified, based on the established criteria. Non-stimulated sialometry was
      performed by the swab technique. Histopathology exams were evaluated for the
      presence of inflammatory focus. RESULTS: Non-stimulated sialometry and minor
      salivary gland biopsy presented different sensitivities for primary Sjogren's
      Syndrome and for secondary Sjogren's Syndrome. Focal sialadenitis with higher
      focus score was characteristic of primary Sjogren's Syndrome. Biopsy and
      sialometry were compared and it was observed that specificity and positive
      predictive value of biopsy were higher. Comparing biopsy and biopsy associated
      with sialometry, it was observed that biopsy had higher sensitivity and negative
      predictive value. Specificity of biopsy associated with sialometry was higher.
      Comparing sialometry and biopsy associated with sialometry, it was observed that
      biopsy associated with sialometry presented higher positive predictive value and
      higher specificity. Sialometry's sensitivity was higher. CONCLUSIONS: Sialometry
      and biopsy tests presented different performances in primary Sjogren's Syndrome
      and secondary Sjogren's Syndrome; the positivity of the association of both tests
      increases the specificity for Sjogren's Syndrome (95%).

PMID- 16446941
TI  - [Endoscopic nasal dacryocystorhinostomy: results and advantages over the external
      approach].
AB  - Dacryocystorhinostomy (DCR) is a procedure used to create a lachrymal drainage
      pathway into the nasal cavity in order to reestablish the permanent drainage of a
      previously obstructed excretory system. AIM: to report our results obtained with
      endoscopic DCR technique, describing its advantages and disadvantages STUDY
      DESIGN: Historic cohort. MATERIAL AND METHOD: we retrospectively analyzed thirty
      two dacryocystorhinostomies performed at the Otorhinolaryngology Discipline from
      March 2002 to January 2004 on patients with post-lachrymal sac obstruction
      confirmed by dacryocystorhinography (DCG). In all cases, the patients were
      submitted to probing with Crawford probe. RESULTS: surgery was bilateral in ten
      of the twenty-two analyzed patients, totaling thirty-two procedures, twenty-nine
      of which were primary surgeries and three revision procedures after unsuccessful
      external DCR. Our success rate was 79.12%. CONCLUSIONS: endoscopic DCR proved to
      be a safe and low morbidity technique, which also avoids facial scars and
      maintains the mechanism of the lachrymal pump, with results similar to those
      obtained with external DCR.

PMID- 16446942
TI  - [Nasal endoscopy associated with paranasal sinus computerized tomography scan in
      the diagnosis of chronic nasal obstruction].
AB  - The chronic nasal obstruction is a common complaint in Otolaryngology
      outpatients. The diagnosis of nasal obstruction is based on the clinical history,
      physical examination and diagnostic procedures. Among these, it is already
      established in the current literature the importance of nasal endoscopy and
      computer tomography scan. AIM: The objective of this research study was based on
      a comparative study among findings of nasal endoscopy and CT scan of the
      paranasal sinuses, within the examinations for etiological investigation in
      chronic nasal obstruction, individualizing the importance of each exam for a
      conclusive diagnosis. STUDY DESIGN: Historic cohort. MATERIAL AND METHOD: Twenty
      patients with chronic nasal obstruction complaints were studied, aged between 14
      and 51 years old in the Otolaryngology outpatient unit at Nossa Senhora de
      Lourdes Hospital, Sao Paulo. It is a retrospective clinical study, carried out by
      revision of medical charts of assisted patients from 2002 to 2004. RESULTS: All
      the patients presented complaints of chronic nasal obstruction. In the 20
      patients, 10 (50%) presented associated allergic complaints. In 16 out of 20
      (80%), patients presented hypertrophic concha evidenced by nasal endoscopy; in
      only 9 out of 20 (45%) patients we found the same affection as in the CT scan.
      Based on the presented results, the finding of hypertrophic concha was more
      evidenced in nasal endoscopy compared to CT (80% X 45%). Two cases of nasal
      polyposis were evidenced in nasal endoscopy but not in CT, besides two other
      cases without detection in the CT, but detected by nasal endoscopy, in other
      words, normal CT with abnormal nasal endoscopy. CONCLUSION: Thus, the presented
      study and the results of nasal fossa findings obtained by nasal endoscopy were
      more conclusive in the elucidation of diagnosis than those obtained by computer
      tomography of the paranasal sinus.

PMID- 16446943
TI  - [Presence of temporomandibular joint discomfort related to pacifier use].
AB  - AIM: The goal of the present study was to analyze if the duration of pacifier use
      influenced the stomatognathic system in children that did not present any other
      parafunctional habits. STUDY DESIGN: Transversal cohort study. MATERIAL AND
      METHOD: To collect data, a questionnaire was used and answered by the mothers of
      90 children aged three to seven years old. RESULTS: The children were divided
      into three groups: did not use pacifier; used pacifier until 2 years old; and
      used pacifier for more than 2 years. Greater prevalence of pain or discomfort in
      the stomatognathic system was observed among the children who had not used
      pacifier and the children who had used it for more than 2 years. The prevalence
      was smaller among the children who used pacifier until 2 years of age.
      CONCLUSION: Thus, it is concluded that pacifier is important to induce children
      to perform suction movements, preparing them to the introduction of solid foods.
      However, if used for a prolonged period of time, it may damage the joint and
      consequently the child's quality of life.

PMID- 16446944
TI  - [Obstructive sleep apnea and hypopnea syndrome: cephalometric analysis].
AB  - Obstructive sleep apnea and hypopnea syndrome (OSAHS) are characterized by
      repeated pauses in breathing during sleep, usually associated with sleep
      interruption and decreased oxyhemoglobin saturation. Cephalometric analysis has
      become an important method in diagnosis, reporting specific craniofacial
      characteristics such as posterior air pharyngeal space, tongue length and hyoid
      position, which may predispose some people to develop SAHOS. The purpose of this
      revision is to present several anatomic aspects by cephalometric analysis that
      may have a predisposition to the development of upper airway occlusion.

PMID- 16446945
TI  - [Agranulocytosis with tonsillitis associated with methimazole therapy].
AB  - The treatment of hyperthyroidism with antithyroid drugs can cause a significant
      side effect in 0.2 to 0.3% of the cases: agranulocytosis. Infectious
      complications caused by this condition affect mainly the throat, and tonsillitis
      is one of its manifestations. The present study reported the case of a female
      patient, 33 years old, manifesting odynophagia and fever resistant to many
      antibiotics. The patient showed hyperthyroidism and had been using methimazole
      for two months. With the diagnoses of agranulocytic angina, the drug was
      withdrawn and treatment with ciprofloxacin, symptomatic drugs and granulocytic
      colony stimulator, besides fluconazol was started. The patient developed
      satisfactorily, being discharged ten days after the beginning of the treatment.
      Fifteen days later, total thyroidectomy was carried out. The purpose of this
      report is to point at the importance of knowing the collateral effects of the
      drugs, to advise the patients about them and worm the doctors about the necessity
      of evaluating the patient as a whole, searching for other current diseases and
      drugs.

PMID- 16446946
TI  - [Mucopyocele of the middle turbinate: a case report].
AB  - Mucopycocele of the middle turbinate is an uncommon disease. Most mucoceles are
      situated in the frontal and/or ethmoid sinuses. In this paper we will describe a
      mucopyocele of the middle turbinate associated with pansinus disease.

PMID- 16446947
TI  - [Vocal fold paralysis in children: diagnostic and management from a case report].
AB  - The vocal fold paralysis accounts for 10% of the larynx congenital abnormality,
      being the second most common cause of laryngeal stridor in childhood. In case the
      unilateral vocal fold paralysis is considered, the main cause is left-sided
      iatrogenic injury to the recurrent laryngeal nerve, secondary to surgery to
      correct the patent ductus arteriosus. In this study we reviewed the literature,
      reporting a case of a child who, after having undergone surgery to close the
      patent ductus arteriosus, evolved with breathing difficulty and dysphonia. We
      suggest that flexible fiberoptic laryngoscopy is carried out pre- and post
      surgery of children for whom heart surgery to correct congenital abnormalities is
      indicated, thus allowing for early diagnosis of vocal fold paralysis and
      therefore to define as soon as possible the conduct to be followed.

PMID- 16446948
TI  - [Enlarged vestibular aqueduct syndrome: report of 3 cases and literature review].
AB  - The Enlarged Vestibular Aqueduct Syndrome is characterized by a widening of the
      vestibular aqueduct, associated with sensorineural hearing loss, or sometimes
      with mixed hearing loss, which may be congenital or acquired during childhood.
      The sensorineural hearing loss may be classified into mild, moderate and severe,
      associated with sudden periods of improvement or aggravation. The enlargement of
      the vestibular aqueduct is the most common inner ear anomaly. This syndrome is
      admitted as a result of a genetic abnormality of the vestibular aqueduct
      development, previous to the fifth week of gestation. The incidence of this
      syndrome ranges from 1% to 1.3%, with the possibility of getting up to 7%,
      depending on the examined population. The aim of this study was to analyze three
      cases of LVAS seen at the Otorhinolaryngology and Radiology Department of Sao
      Camilo Hospital - Sao Paulo. Two of these three cases were of brothers, from the
      same mother but from different fathers. Two were male and one was female and the
      ages ranged from 9 to 30 years old. The diagnosed method of election was CT,
      Computerized Tomography of the temporal bones. The procedure for the cases was
      that of observation, with exception for those of cranial traumatisms, barotraumas
      and, when necessary, the use of auditive prosthesis.

PMID- 16446949
TI  - [Endoscopic treatment of odontogenic cyst with intra-sinusal extension].
AB  - Odontogenic cyst is a common lesion that can happen after inflammation of the
      dental pulp. The therapeutic approach of these cysts is made at dentist's
      offices, and depending on their extension, they may develop oroantral fistula and
      chronic sinusitis. The objective of this study is to propose the videoendoscopic
      treatment of the odontogenic cyst with expression in the maxillary sinus. We made
      a retrospective study of four cases of cysts of dental origin, with intra-sinusal
      extension, complicated with oroantral fistula and chronic sinusitis of maxillary
      sinus after curettage in a dentist's office. We used the videoendoscopic
      technique through transmaxillary approach to access the intra-sinusal cyst. All
      the four patients presented resolution of the infectious manifestation and
      healing of the oroantral fistula, without recurrence within two years of follow
      up. Videoendoscopic surgery is a safe and effective method for the management of
      odontogenic cysts with extension to maxillary sinus, and it may prevent oroantral
      fistula formation and chronic sinusitis.

PMID- 16446950
TI  - [Middle ear squamous papilloma: report of a case and literature review].
AB  - Squamous papillomas are benign neoplasms. The occurrence of middle ear squamous
      papilloma is rare. It is usually associated with nasosinusal pathology. The
      authors report a case of middle ear squamous papilloma and discuss its diagnostic
      aspects.

PMID- 16446951
TI  - Nice to meet you, law of innovation...

PMID- 16446952
TI  - Microscopic anatomy of the carotid canal and its relations with cochlea and
      middle ear.
AB  - The knowledge of the relations between the noble and vital structures of temporal
      bone is still a great challenge for the otologic surgeon. The microscopic
      anatomic studies of the temporal bone are one of the greatest help to prevent
      lesions during surgical intervention. AIM: To study the anatomic correlations
      between the carotid canal and the cochlea, and the occurrence of dehiscence of
      the carotid canal in the middle ear tympanic cavity. MATERIAL AND METHODS:
      Microscopic study of 122 human temporal bones. RESULTS: The average distance
      between the carotid canal and the cochlea were: the shortest distance, 1.05 mm;
      basal turn, 2.04 mm; middle turn, 2.32 mm; and apical turn, 5.70 mm. The
      occurrence of dehiscence of the carotid canal inside the tympanic cavity was
      35.2%. CONCLUSION: The small distances between the cochlea and carotid canal, and
      the high incidence of dehiscence in the tympanic cavity remind us that anatomical
      knowledge of the temporal bone is required for the best qualification of
      otologists.

PMID- 16446953
TI  - Tympanostomy tube sequelae in children with otitis media with effusion: a three
      year follow-up study.
AB  - Tympanostomy tube (TT) insertion is one of the most frequently performed
      procedures in otolaryngology. Otorrhea, tympanosclerosis, retraction,
      perforation, and cholesteatoma are complications reported in the literature after
      its application. AIM: To determine the incidence and the type of TT insertion
      sequelae/complications in children presenting with recurrent otitis media and
      chronic otitis media with effusion undergoing myringotomy and tube placement.
      STUDY DESIGN: Prospective cohort study. MATERIAL AND METHOD: A total of 75
      children (150 ears) aged 11 months to 10 years were regularly followed up for up
      to 38 months after TT insertion. RESULTS: Incidence of sequelae/complications:
      otorrhea--47.3% of the ears; perforation--2.1%; retractions--39.7%;
      tympanosclerosis--23.3%. Average length of stay: 12.13 months. Mean age at
      initial tube placement of children not requiring a second set of tubes = 35.9
      months and mean age at initial tube insertion of children requiring an additional
      set of tubes = 25.6 months (P = 0.04). TT stayed longer in the ears that had more
      episodes of otorrhea (P = 0.01). TT insertion with adenoidectomy was associated
      with a smaller number of otorrhea episodes (P = 0.02) CONCLUSIONS: Otorrhea was
      the most frequently found complication. TT placement with adenoidectomy was
      associated with fewer otorrhea episodes. TT extruded later in those ears that had
      more episodes of otorrhea. Younger age at the time of the initial tube placement
      is associated with higher incidence of additional tube placement. One in six
      patients will probably require a second set of ventilation tubes.

PMID- 16446954
TI  - Magnetic resonance imaging in sudden deafness.
AB  - The etiology of sudden deafness can remain undetermined despite extensive
      investigation. This study addresses the value of magnetic resonance imaging in
      the analysis of sudden deafness patients. STUDY DESIGN: Transversal cohort.
      MATERIAL AND METHOD: In a prospective study, 49 patients attended at
      otolaryngology emergency room of Federal University of Sao Paulo--Escola Paulista
      de Medicina, from April 2001 to May 2003, were submitted to magnetic resonance
      imaging. RESULTS: Magnetic Resonance abnormalities were seen in 23 (46.9%)
      patients and revealed two tumors suggestive of meningioma, three vestibular
      schwannomas, thirteen microangiopathic changes of the brain and five (21.7%)
      pathological conditions of the labyrinth. CONCLUSION: Sudden deafness should be
      approached as a symptom common to different diseases. The presence of
      cerebellopontine angle tumors in 10.2% of our cases, among other treatable
      causes, justifies the recommendation of gadolinium-enhanced magnetic resonance
      use, not only to study the auditory peripheral pathway, but to study the whole
      auditory pathway including the brain.

PMID- 16446955
TI  - Tinnitus in normally hearing patients: clinical aspects and repercussions.
AB  - Patients with tinnitus and normal hearing constitute an important group, given
      that findings do not suffer influence of the hearing loss. However, this group is
      rarely studied, so we do not know whether its clinical characteristics and
      interference in daily life are the same of those of the patients with tinnitus
      and hearing loss. AIM: To compare tinnitus characteristics and interference in
      daily life among patients with and without hearing loss. STUDY DESIGN: Historic
      cohort. MATERIAL AND METHOD: Among 744 tinnitus patients seen at a Tinnitus
      Clinic, 55 with normal audiometry were retrospectively evaluated. The control
      group consisted of 198 patients with tinnitus and hearing loss, following the
      same protocol. We analyzed the patients' data as well as the tinnitus
      characteristics and interference in daily life. RESULTS: The mean age of the
      studied group (43.1 +/- 13.4 years) was significantly lower than that of the
      control group (49.9 +/- 14.5 years). In both groups, tinnitus was predominant in
      women, bilateral, single tone and constant, but there were no differences between
      both groups. The interference in concentration and emotional status (25.5% and
      36.4%) was significantly lower in the studied group than that of the control
      group (46% and 61.6%), but it did not happen in regard to interference over sleep
      and social life. CONCLUSIONS: Patients with tinnitus and normal hearing showed
      similar characteristics when compared to those with hearing loss. However, the
      age of the patients and the interference over concentration and emotional status
      were significantly lower in this group.

PMID- 16446956
TI  - Evaluation of speech perception in noise in cochlear implanted adults.
AB  - AIM: To evaluate the effects of different signal-to-noise ratios on speech
      recognition obtained by the use of cochlear implant (CI); to compare the speech
      recognition in noise with different types of multichannel cochlear implants (CIs)
      and to evaluate the degree of difficulty for speech understanding in noise in
      daily life situations. STUDY DESIGN: Cohort transversal. MATERIAL AND METHOD:
      Forty adults with post-lingual hearing loss implanted with Nucleus 22, Nucleus
      24, Combi 40, Combi 40+ and Clarion. We evaluated the recognition for CPA
      sentences in quiet and in S/N +15, +10 and +5 dB. We also applied the Social
      Hearing Handicap Index (SHHI) questionnaire for self-assessment in daily life.
      RESULTS AND CONCLUSION: All the implanted adults presented a significant
      reduction in the scores for sentences recognition as the S/N decreased. The
      medians' curve for sentence recognition reached 50% in the signal-to-noise ratio
      of +10 dB. There was no statistically significant difference in sentences'
      recognition scores and difficulty scores obtained with the SHHI, for all types of
      implants. The difficulties of implanted adults were rare in quiet and occasional
      in noisy situations according to SHHI questionnaire.

PMID- 16446957
TI  - Personalized vestibular rehabilitation: medical chart survey with patients seen
      at the ambulatory of otoneurology of I.S.C.M.S.P.
AB  - The objective of this research study was to verify the efficiency of the
      personalized vestibular rehabilitation (PVR) in different otoneurologic clinical
      diseases, as well as set the best protocol option in each case. STUDY DESIGN:
      Clinical retrospective. MATERIAL AND METHOD: A retrospective study was conducted
      based on the description of the vestibular rehabilitation program of 37 patients
      aged 21 to 87 years, twenty-six females and eleven males, with different clinical
      diseases seen in the Otoneurologic Ambulatory of Otolaryngology, department of
      Irmandade da Santa Casa de Misericordia de Sao Paulo, from 2002 to 2003. Those
      patients went through otoneurologic evaluation and after diagnosis they were
      referred to vestibular rehabilitation. Each patient followed a specific program
      based on diagnosis, clinical disease and symptoms. We performed an individual
      analysis of the evaluation of each patient and group analysis in order to verify
      the efficiency of the PVR. CONCLUSION: It was possible to conclude that the PVR
      program is an effective resource in the treatment of otoneurologic symptoms of
      patients, consequently improving their quality of life.

PMID- 16446958
TI  - Posture control in Pusher syndrome: influence of lateral semicircular canals.
AB  - Pusher syndrome is an interesting disorder of balance in patients with encephalic
      lesions characterized by the peculiar behavior of actively pushing away from the
      non-hemiparetic side and resisting against passive correction, with a tendency to
      fall toward the paralyzed side. The role of vestibular system on the pushing
      behavior is not clear. AIM: To evaluate horizontal semicircular canal function in
      patients with Pusher syndrome, using caloric and rotation tests. STUDY DESIGN:
      Observational prospective. MATERIAL AND METHOD: We evaluated 9 inpatients with
      stroke and Pusher syndrome at the neurological unit of HCFMRP-USP. We applied
      neurological and neuropsychological exams, NIHSS, Scale for contraversive pushing
      (SCP), caloric and rotation tests. RESULTS: We evaluated 9 patients (5 men) with
      mean age of 71.8 +/- 5.9 and mean NIHSS of 18.33. Three patients presented
      contralateral directional preponderance on caloric test and we found four
      patients with directional preponderance on analysis of the slow phase velocity of
      rotation test response. CONCLUSION: Our findings indicate that a dysfunction of
      semicircular canals does not seem to be relevant for the clinical manifestations
      of the Pusher syndrome.

PMID- 16446959
TI  - The value of prognostic clinical data in Bell's palsy.
AB  - Electroneurography (ENoG) and clinical staging are currently the methods of
      choice to indicate prognosis in Bell's palsy, although ENoG is an
      electrophysiological test not universally available. AIM: Identify other options
      of prognostic evaluation based upon clinical aspects and minimal electrical
      stimulation test allowing prognostic measurement in almost any circumstances.
      STUDY DESIGN: Historic cohort. MATERIAL AND METHOD: Chart review of 1,521 cases
      of IPFP, analyzing the following clinical aspects: gender, age, paralyzed side,
      installation mode, previous symptoms, associated symptoms and minimal electrical
      stimulation test (Hilger test) and its statistical correlation to facial palsy
      evolution after 6 months. RESULTS: Data indicated that patients above 60 years
      old had worse prognosis in comparison with patients under 30 years old. A
      progressive mode of paralysis installation, absence of previous symptoms,
      concomitant vertigo and response superior to 3.5 mA at minimum electrical
      stimulation test were also related to worse prognosis. On the other hand, the
      absence of concomitant symptoms, diminished tearing and sudden onset were related
      to better prognosis. CONCLUSION: Clinical factors and Hilger's test can
      accurately indicate the prognosis in cases of Bell's palsy when ENoG is not
      available.

PMID- 16446960
TI  - Effect of mitomycin C on the secretion of granulocyte macrophages colonies
      stimulating factor and interleukin-5 in eosinophilic nasal polyps stromal
      culture.
AB  - The research involving tissue factors, such as granulocyte macrophage colonies
      stimulating factor (GM-CSF) and interleukin 5 (IL-5), leads to the mechanisms
      involved in the maintenance of eosinophilia, which is essential for the
      pathogenesis on eosinophilic nasal polyps. Mitomycin C has been successfully used
      in otolaryngology. AIM: The objective of this study was to evaluate the effect of
      mitomycin C in secretion of GM-CSF and IL-5 on eosinophilic nasal polyps. STUDY
      DESIGN: Case-control. MATERIAL AND METHOD: This is a comparative and auto-matched
      experimental study, performed with fragments of polyps which had been obtained
      from biopsy of patients with eosinophilic nasosinusal polyposis. The fragments of
      the experimental group were treated with mitomycin C (400 microg/ml) for 5
      minutes and then washed in RPMI substrate. At time zero, 12 and 24 hours, the
      surface material was taken to determination of its GM-CSF levels in 22 patients
      and of IL-5 levels in 19 patients, by ELISA method. RESULTS: Reduction in GM-CSF
      expression on the experimental group at time 24 h (p< or = 0.05). The treated
      group presented significant GM-CSF expression between zero time and 12 h time (p=
      0.013) showing the culture viability such as in the non-treated group. Tendency
      to decreasing IL-5 levels on the treated groups at 24 hours. CONCLUSION: This
      study showed that mitomycin C was efficient in inhibiting GM-CSF synthesis with
      reduction of IL-5 secretion, but this fact needs complementary studies.

PMID- 16446961
TI  - Epidemiological analysis of structural alterations of the nasal cavity associated
      with obstructive sleep apnea syndrome (OSA).
AB  - AIM: The objective of this paper is to demonstrate that structural alterations of
      the nasal cavity, e.g. septal deviation and conchal hypertrophy have high
      incidence in patients with sleep apnea and hypopnea syndrome and must be
      addressed with associated specific procedures of the syndrome. TYPE OF STUDY:
      Clinical retrospective. CASUISTIC AND METHOD: A retrospective study of 200
      patients was performed, with 196 male and 4 female, attended at the
      otorhinolaryngology ambulatory of Hospital Prof. Edmundo Vasconcelos and Unidade
      Paulista de Otorrinolaringologia, all of them subjected to polysomnography,
      otorhinolaryngological physical exam, endoscopy exam, and surgical treatment with
      nasal and pharyngeal procedures. RESULTS: All of them were subjected to
      pharyngeal procedure: uvulopalatopharyngoplasty or uvulopalatoplasty and nose
      procedure: 176 septoplasty with partial turbinectomy (88%) and 24 isolated
      turbinectomy, with satisfactory results. CONCLUSION: We can see that structural
      alterations of the nasal cavity have high incidence in patients with OSA.

PMID- 16446963
TI  - Endoscopic repair of CSF rhinorrhea: experience of 44 cases.
AB  - Cerebrospinal fluid (CSF) rhinorrhea is a leakage of fluid from the subarachnoid
      space to the frontal, sphenoidal or ethmoidal sinuses. CSF rhinorrhea is a known
      potential complication with significant morbidity and mortality. It may present a
      significant challenge in diagnosis, localization and management. STUDY DESIGN:
      Series study. MATERIAL AND METHOD: Between 1993 and 2004, 44 patients with
      cerebrospinal rhinorrhea were operated on using intranasal endoscopic approach in
      the University Hospital of the University of Sao Paulo, Medical School. The
      charts of all patients treated in our hospital were reviewed. RESULTS: Forty-four
      patients, 16 women (36%) and twenty-eight men (64%), were included in the study.
      Patients' ages ranged from 2 to 68 years (mean: 40.3 years). Etiology, site of
      leakage, diagnosis, technique, cause of failure and follow-up are discussed.
      CONCLUSION: The authors concluded that transnasal endoscopic surgery for CSF
      rhinorrhea had high success rate, low morbidity and stable long-term results.

PMID- 16446962
TI  - Assessment of pre and postoperative symptomatology in patients undergoing
      inferior turbinectomy.
AB  - Partial inferior turbinectomy is a procedure directed to treat nasal obstruction
      secondary to hypertrophy rhinitis. This study evaluates the impact of this
      procedure in the quality of life of the patients, analyzing the improvement of
      other symptoms such as rhinorrhea, nasal itching and sneezing after six months of
      the surgical procedure. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD:
      Forty-nine patients submitted to turbinectomy associated or not with septoplasty,
      received questionnaires to grade the intensity of symptoms. Through the
      comparison of severity of symptoms before and after six months of the surgery, it
      was possible to evaluate the degree of improvement of each symptom. The results
      were classified as null, good, moderate and great, and we subtracted
      postoperative score from the preoperative score. RESULTS: The nasal obstruction
      presented good or great results in 98% of the patients. For rhinorrhea, the
      surgery has resulted in good or great improvement in 49% of the cases. Sneezing
      presented good or great results in 81.6% of the patients and, nasal itching, 45%.
      CONCLUSION: The study showed that the clinical benefits obtained with the partial
      inferior turbinectomy are not limited to nasal obstruction, extending also to
      others symptoms of rhinitis, mainly in relation to sneezing crisis.

PMID- 16446964
TI  - Effects of posture change on nasal patency.
AB  - Nasal obstruction when lying down frequently brings patients to the
      otolaryngologic clinic. There are several explanations for the problem. The nasal
      mucosa reaction to venous changes that alter local blood flow, secondary to
      compression of the neck veins or hydrostatic pressures, is the most accepted
      explanation. Acoustic rhinometry is a new non-invasive technique to assess nasal
      patency. AIM: The purpose of this study was to assess the effect of posture
      change from sitting to supine position applying acoustic rhinometry. STUDY
      DESIGN: Clinical prospective. MATERIAL AND METHOD: 10 volunteers with no nasal
      disorders, aged 19 to 30 years old, and 10 volunteers with symptoms of rhinitis,
      aged 18 to 27 years old, were selected for the study. Nasal sensation was tested
      by means of a visual analogue scale. Nasal area and volume were assessed by
      acoustic rhinometry in the following positions: seated and 15 minutes after lying
      down. RESULTS: Both groups showed significant nasal obstruction on the visual
      analogue scale and on acoustic rhinometry. The perception of nasal obstruction
      was significantly higher in subjects with rhinitis symptoms compared to normal.
      CONCLUSION: We conclude that the effect of posture change from sitting to supine
      position produces a decrease in nasal cross-sectional area and volume in both
      normal and in subjects with symptoms of rhinitis. However, the impact on the
      perception of nasal obstruction induced by lying down seems to be higher in
      subjects with symptoms of rhinitis.

PMID- 16446965
TI  - Immunohistochemistry as a method to study elastic fibers of human vocal fold.
AB  - AIM: Verify the use of immunohistochemistry as a method to measure all forms of
      elastic fibers at human vocal folds. STUDY DESIGN: Transversal cohort. MATERIAL
      AND METHOD: We collected vocal folds following these criterion: age between 25
      and 40, Caucasian men, dead by gun shot, within 12 hours of death, without
      instrumentation of the larynx or suspicion of neck injury and without mucosal
      lesions noted by microscopy. Ten vocal folds were collected and one, of a man
      aged 28 years, was selected to study. The vocal fold was transversely cut in 9
      regions and in each segment three slides were made. These slides were stained by
      Verhoeff and Weighert's resorcin-fuchsin and used for immunohistochemistry. The
      elastic compound was measured by colorimetric software analysis. RESULTS: In
      Verhoeff and Weighert's resorcin-fuchsin, the intermediate and deep layer showed
      values higher than those of the superficial layer. The amount of tropoelastin
      identified by the antibody at the superficial layer was close to those of
      intermediate and deep layer. CONCLUSION: Immunohistochemistry is a method that
      can identify and measure all forms of elastic fibers at human vocal fold.

PMID- 16446966
TI  - Vocal process granuloma: clinical characterization, treatment and evolution.
AB  - Vocal process granuloma is a disease whose etiopathogenesis is not well defined.
      Therefore, its clinical and surgical treatment is not standardized and its
      therapeutic results depend on the hospital where it is seen. AIM: Aiming to
      characterize patients with vocal process granuloma treated in our hospital, the
      therapeutic approach used and clinical evolution. MATERIAL AND METHOD: We
      performed a retrospective review of records. RESULTS: We found more male vocal
      process granuloma, except when associated with laryngeal intubation. The most
      frequent related etiopathogenic factor was laryngeal-pharynx reflux, followed by
      laryngeal intubation and vocal abuse. Clinical management with proton-pump
      inhibitor (PPI), topical inhalant steroid and phonotherapy was enough for
      remission on 48.6% of the patients. Surgery for removal of the granuloma
      associated with clinical management was effective in 90% of the events. Later
      recurrences (more than one year) were noticed in five patients, suggesting that
      associated etiopathogenic factors should be held for a long time.

PMID- 16446967
TI  - Laryngeal assessment in rheumatic disease patients.
AB  - Rheumatic diseases usually promote several systemic disorders, which can affect
      blood vessels, mucosa and serosa of the aerodigestive tract. Scarce laryngeal
      involvement has been described in these patients and this study aims at
      investigating laryngeal alterations found in patients with rheumatic diseases.
      STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: A transversal study was
      developed with systemic lupus erythematous, systemic sclerosis and mixed
      connective tissue disease's patients. They were evaluated by means of clinical
      examinations and videolaryngoestroboscopy. RESULTS: Twenty-seven patients were
      included in the study, 26 succeeded in completing the videolaryngoestroboscopy.
      Laryngeal abnormalities were seen in 11 of 12 patients with lupus, in all 11
      patients with sclerodermia and in 3 patients with mixed connective tissue
      disease. Vocal fold bamboo node was observed in 5 patients and 92.3% of all
      patients presented laryngeal signs of gastroesophageal reflux disease.
      CONCLUSION: We noticed 5 vocal fold bamboo nodes and gastroesophageal reflux
      disease in almost all patients.

PMID- 16446968
TI  - Speech rehabilitation after total laryngectomy: long-term results with indwelling
      voice prosthesis Blom-Singer.
AB  - To evaluate long-term use of indwelling Blom-Singer voice prosthesis (VP) for
      vocal rehabilitation of patients submitted to total laryngectomy (TL). We studied
      the influence of time of performance of tracheo-esophageal puncture (TEP), use of
      radiotherapy (XRT), patients' age and length of follow-up, on the rate of success
      of use of VP. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: Seventy
      one patients were submitted to TL and rehabilitated with indwelling VP. Both
      otolaryngologist and speech pathologist evaluated all patients for the vocal
      functional issues during the follow-up. The relative data on time of placement of
      VP, time of use of PF, use of XRT, age, length of follow-up and interval of
      duration of each VP were recorded during the follow-up. RESULTS: There was 87% of
      patients with primary TEP and 13% with secondary. The follow-up varied from 12 to
      87 months, with average of 38 months for primary and 51 months for secondary TEP.
      There were 59% of patients submitted to XRT. The general rate of success was of
      94%. In primary TEP it was of 97% and in the secondary, it was 78% (p=0.07) and
      after two years, the success rate was of 96% in primary TEP and 75% in secondary
      TEP (p=0.07). The use of XRT and patient age did not influence the success of use
      of VP among primary and secondary TEP, independently of length of follow-up.
      CONCLUSION: Tendency to greater success rate in voice rehabilitation after TL
      with primary TEP was observed. Postoperative XRT and age did not influence
      success rate.

PMID- 16446969
TI  - Prevalence of histological findings of human papillomavirus (HPV) in oral and
      oropharyngeal squamous cell carcinoma biopsies: preliminary study.
AB  - Human papillomavirus (HPV) is considered to be an etiologic agent of cervical
      cancer and, recently its relation to oral and oropharyngeal cancer has also been
      investigated. Oral squamous cell carcinoma (SCC) represents 90% of all malignant
      tumors that affect the oral cavity. The prevalence of HPV in patients with SCC
      ranges from 0 to 100%. The most known viral cytopathic effect is koilocytosis,
      considered to be a major characteristic of HPV infection. AIM: The aim of this
      study was to verify the prevalence of some peculiar characteristics of HPV-
      koilocytosis--in oral and oropharyngeal SCC. STUDY DESIGN: Transversal cohort.
      MATERIAL AND METHOD: Twenty slides with oral and/or oropharyngeal SCC were
      examined under microscopy. RESULTS: In 15 of them, koilocytosis was found,
      amounting to 75%. Although we know that polymerase chain reaction (PCR) is the
      method with the best sensitivity for HPV detection, we began this research
      looking for koilocytosis, which is highly suggestive of HPV infection.
      CONCLUSION: This study is a trial project and we will continue this research with
      PCR measures to confirm this high prevalence of HPV infection in oral and
      oropharyngeal SCC.

PMID- 16446970
TI  - AIDS and Recurrent Aphthous Stomatitis.
AB  - The immunodeficiency state in HIV infected patients has been the cause of severe
      episodes of Recurrent Aphthous Stomatitis (RAS). AIM: Our study aims to establish
      correlation between the manifestations of RAS and the immunosuppression state
      caused by HIV infection, through counting of CD4+ cells, CD8+ cells, CD4+:CD8+
      cells ratio and viral load. STUDY DESIGN: Series study. MATERIAL AND METHOD:
      Ninety-four HIV infected patients (25 women and 69 men) with RAS were evaluated
      in the ENT Department of the University of Sao Paulo-Medical School from January
      1998 to December 2003. The age ranged between 19 and 63 years (mean = 35.3
      years). The patients were divided in two groups: AIDS group and HIV infected
      group. RESULTS: The patients with AIDS and HIV infection presented, respectively,
      eight ulcers and two ulcers by outbreaks. Similarly, patients with major RAS
      presented smaller counting of cells CD8+, CD4+ and CD4+/CD8+ cells, and higher
      mean value of viral load than the patients with herpetiform and minor RAS.
      Between patients with minor and herpetiform RAS there were no statistical
      differences. CONCLUSIONS: The emergence of the lesions, mainly in major RAS, is
      directly related to the immunological state of the HIV infected patient. These
      patients frequently present nutritional deficits and worsening in life style.
      Thus, diagnosis and treatment of RAS is a challenge that should not be neglected.

PMID- 16446971
TI  - Pre and postoperative psychological profile of children submitted to
      adenoidectomy and/or tonsillectomy.
AB  - Adenoidectomy and/or tonsillectomy are the most frequent surgeries in
      otorhinolaryngology. Infantile psychological trauma may be caused by surgeries
      and anesthesia. AIM: To estimate the preoperative service offered to children and
      their responsible people by examining their psychological profile pre and
      postoperatively. STUDY DESIGN: Clinical perspective. MATERIAL AND METHOD: We have
      evaluated the medical chart of children between two and twelve years old who were
      submitted to adenoidectomy and/or tonsillectomy during February to December of
      2003 and analyzed the psychological profile applied to the children and their
      responsible person. RESULTS: Out of the total of 78 patients, 32 (41.0%) were in
      pre-school age and 46 (59.0%) in school age. The predominant feeling in pre
      school age was fear (59.4%), while in school-aged children and their responsible
      guardian it was trust: 63.0% and 48.72%, respectively. As to expectation of
      surgery results, both children (73.08%) and their responsible people (96.15%)
      showed optimism. Introverted emotional temperament was observed in the majority
      of the children (52.56%) and their responsible people (51.28%). The emotional
      reaction at the immediate postoperative period of children and their guardians
      was calm: 68.18% and 97.73%, respectively. All children were psychologically apt
      to be submitted to the surgery. CONCLUSION: Independent of the predominant
      feeling or emotional temperament, good preoperative guidance is required. We have
      to offer preoperative teaching program that includes verbal descriptions of the
      procedures among the sensations to be experienced, allied with the interaction of
      children and parents, looking for reduction of anxiety, response to surgical
      stress and possible postoperative sequelae.

PMID- 16446972
TI  - Craniofacial pain and anatomical abnormalities of the nasal cavities.
AB  - The causal relation between anatomical variations of the nose and headaches and
      facial pain is analyzed through literature review of the topic. The pathogenesis
      that can be involved in this relation proves to be wider than simple alteration
      of nasal septum and turbinates that can cause mechanical stimulus through contact
      between these structures, which covers infectious factors, neurogenic
      inflammation, correlation with migraines and the role of nasal obstruction. The
      clinical findings of a lot of authors including the test with topical anesthetic
      to prove this causal relation, the indication of surgical treatment, in addition
      to good results of this treatment, are reported. The mechanism of pain relief
      obtained through surgical correction of nasal septum and turbinate is discussed.
      These data make us conclude that there are multiple etiologic factors involved,
      which makes us question the fundamental role of the mechanical aspect.

PMID- 16446973
TI  - Some considerations about acquired adult and pediatric cholesteatomas.
AB  - Authors debate about cholesteatomas, from the first time this word was employed,
      by Muller, in 1838, until the recent updates. They dissert about its definition,
      etiology and pathology and present basic concepts about its biology. They also
      make a wide review about pediatric cholesteatoma, its epidemiology and biology,
      and compare it with adult cholesteatoma. Finally, they describe some articles
      about ossicle chain erosion and its correlation with cholesteatoma perimatrix,
      collagen and collagenase.

PMID- 16446974
TI  - Identification of functional single nucleotide polymorphism haplotypes in the
      cytidine deaminase promoter.
AB  - Cytidine deaminase (CDA) hydrolytically deaminates and irreversibly deactivates
      the chemotherapeutic agent cytosine arabinoside (Ara-C), a deoxycytidine analog
      used for treatment of acute leukemias and lymphomas. To determine if single
      nucleotide polymorphisms (SNPs) in the promoter region of CDA affected gene
      expression, we sequenced approximately 1.6 Kb upstream of the CDA translation
      initiation site and containing the proximal promoter of CDA. We identified 6
      SNPs; -92A>G, -205C>G, -451C>T, -897C>A, -1075A>G and -1181G>A. Based on
      predicted changes in transcription factor binding sites, three SNPs (-92A>G, 
      451C>T and -897C>A) were chosen for further investigation. The five haplotypes
      segregating in the population were cloned into a luciferase expression plasmid,
      transfected into Cos-1 cells and reporter activity measured at 24 and 48 h. Four
      haplotypes showed an average expression which was 2.5-fold higher at 24 h
      (P<0.0001) and 3.3-fold higher at 48 h (P<0.0001) than the lowest expressing
      haplotype. When reanalyzed as single SNP genotypes, the differences in expression
      were significant, except for -897 C/A, at 24 h, but the magnitude of difference
      was reduced, suggesting that no single SNP completely accounts for the expression
      differences observed at the haplotype level. As predicted from the in vitro
      analysis, individuals homozygous for common haplotype (ACC/ACC) showed higher
      levels of CDA enzymatic activity as individuals heterozygous for the wild type
      and low expressing haplotype (ACC/ATC). As CDA promoter region haplotypes may
      influence Ara-C chemosensitivity, shown here in in vitro and in vivo studies, the
      clinical relevance of these findings should be examined.

PMID- 16446975
TI  - Genetic alterations in caspase-10 may be causative or protective in autoimmune
      lymphoproliferative syndrome.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is characterized by
      lymphadenopathy, elevated numbers of T cells with alphabeta-T cell receptors but
      neither CD4 nor CD8 co-receptors, and impaired lymphocyte apoptosis in vitro.
      Defects in the Fas receptor are the most common cause of ALPS (ALPS Ia), but in
      rare cases other apoptosis proteins have been implicated, including caspase-10
      (ALPS II). We investigated the role of variants of caspase-10 in ALPS. Of 32
      unrelated probands with ALPS who did not have Fas defects, two were heterozygous
      for the caspase-10 missense mutation I406L. Like the previously reported ALPS II
      associated mutation L285F, I406L impaired apoptosis when transfected alone and
      dominantly inhibited apoptosis mediated by wild type caspase-10 in a co
      transfection assay. Other variants in caspase-10, V410I and Y446C, were found in
      3.4 and 1.6% of chromosomes in Caucasians, and in 0.5 and <0.5% of African
      Americans, respectively. In contrast to L285F and I406L, these variants had no
      dominant negative effect in co-transfection assays into the H9 lymphocytic cell
      line. We found healthy individuals homozygous for V410I, challenging the earlier
      suggestion that homozygosity for V410I alone causes ALPS. Moreover, an
      association analysis suggested protection from severe disease by caspase-10 V410I
      in 63 families with ALPS Ia due to dominant Fas mutations (P<0.05). Thus,
      different genetic variations in caspase-10 can produce contrasting phenotypic
      effects.

PMID- 16446976
TI  - Genetic linkage of human height is confirmed to 9q22 and Xq24.
AB  - Human height is an important and heritable trait. Our previous two genome-wide
      linkage studies using 630 (WG1 study) and an extended sample of 1,816 Caucasians
      (WG2 study) identified 9q22 [maximum LOD score (MLS)=2.74 in the WG2 study] and
      preliminarily confirmed Xq24 (two-point LOD score=1.91 in the WG1 study, 2.64 in
      the WG2 study) linked to height. Here, with a much further extended large sample
      containing 3,726 Caucasians, we performed a new genome-wide linkage scan and
      confirmed, in high significance, the two regions' linkage to height. An MLS of
      4.34 was detected on 9q22 and a two-point LOD score of 5.63 was attained for
      Xq24. In an independent sub-sample (i.e., the subjects not involved in the WG1
      and WG2 studies), the two regions also achieved significant empirical P values
      (0.002 and 0.004, respectively) for "region-wise" linkage confirmation.
      Importantly, the two regions were replicated on a genotyping platform different
      from the WG1 and WG2 studies (i.e., a different set of markers and different
      genotyping instruments). Interestingly, 9q22 harbors the ROR2 gene, which is
      required for growth plate development, and Xq24 was linked to short stature. With
      the largest sample from a single population of the same ethnicity in the field of
      linkage studies for complex traits, our current study, together with two previous
      ones, provided overwhelming evidence substantiating 9q22 and Xq24 for height
      variation. In particular, our three consecutive whole genome studies are uniquely
      valuable as they represent the first practical (rather than simulated) example of
      how significant increase in sample size may improve linkage detection for human
      complex traits.

PMID- 16446978
TI  - Shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a
      prospective study.
AB  - We performed a prospective, non-randomised study to determine the appropriate
      first-line treatment modality for distal ureteral stones. Between 2003 and 2004,
      a total of 124 patients with distal ureteral calculi were entered into the study
      (mean age 48 years, 35 women and 99 men). Sixty-two patients were treated with
      shock wave lithotripsy (SWL) and 62 patients with ureteroscopy (URS). The average
      stone size was 6.9 mm (3-33 mm) for SWL and 7.2 mm (3-30 mm) for URS. The
      treatment decision depended on the patients' preference and clinical parameters
      (i.e. contraindications for anaesthesia). URS was performed under general
      anaesthesia, using semirigid 8 Fr instruments. SWL was performed under analgo
      sedation using a Modulith SLX. Of patients treated with SWL, 84% had a treatment
      success within 7 days, 98% after URS. These results show a significant success
      (P=0.005) in favour of URS. The average in-patient stay after SWL was 3 days and
      for URS 4 days (not significant). The results show a high efficacy and a low
      complication rate for both modalities. The attained stone-free rate shows a
      significant advantage for primary URS.

PMID- 16446977
TI  - Evidence of transmission ratio distortion of DLG5 R30Q variant in general and
      implication of an association with Crohn disease in men.
AB  - Recently, we described the association of genetic variation in the discs large
      homolog 5 (DLG5) gene with inflammatory bowel disease (IBD) in a large European
      study sample (Stoll et al. in Nat Genet 36:476-480, 2004). Here, we report that
      the R30Q variant constitutes a susceptibility factor for Crohn disease (CD) in
      men [odds ratio (OR)=2.49, 95% confidence interval (CI) 1.53-4.06, P<0.001] but
      not women (OR=1.01, 95% CI=0.70-1.45, P=0.979) using multivariate logistic
      regression analyses in a unified study sample from Germany, Italy and Quebec.
      R30Q is a significant predictor for CD in men even when accounting for CARD15 and
      IBD5 risk variants (adjusted OR=2.41, 95% CI=1.41-4.12, P=0.001). The observed
      association is driven by a gender-dependent transmission ratio distortion (TRD)
      among healthy controls (frequency of Q allele: men 5.2%, women 11.3%), an effect
      that is offset in CD patients (frequency of Q allele: men 10.1%, women 10.9%).
      This finding is further substantiated by two non-IBD study samples, one of which
      consists of a newborn screening sample (newborn males 7.1%; newborn females 11%,
      P=0.036). Further investigation of the observed TRD may contribute towards
      enlightening the role of DLG5 in physiological processes influencing transmission
      of chromosomes to the surviving offspring, which, in turn, may help in
      understanding its implication in the development of CD among men.

PMID- 16446979
TI  - Re: Ex vivo model training for percutaneous surgery.

PMID- 16446980
TI  - Shockwave lithotripsy and endourological stone treatment in children.
AB  - Urolithiasis in children is a rare disease in developed countries. Due to the
      particular anatomical conditions of the infant body, indications and results of
      the well-known treatment modalities, such as shockwave lithotripsy (SWL),
      ureteroscopy and PCNL, have to be determined. Experience in active stone
      treatment in children is very rare and only a limited number of papers are
      available. SWL can be performed only if focus size and treatment facilities are
      adapted to the size of the child. Miniaturization of ureteroscopes allows primary
      access to the infant upper urinary tract. Results, complications and morbidity of
      the treatment are similar to the results in adults. The main prerequisite for the
      primary endoscopic approach is the experience of the surgeon. PCNL should be
      performed as Mini-Perc. Percutaneous procedures show equal results and morbidity
      compared to the treatment of adults, in experienced hands. As two-thirds of
      infant stone patients have an underlying metabolic disorder, close cooperation of
      adult and pediatric urologists, nephrologists and radiologists is necessary in
      order to achieve good results in the treatment of infant stones.

PMID- 16446983
TI  - Geometric partition functions of cellular systems: explicit calculation of the
      entropy in two and three dimensions.
AB  - A method is proposed for the characterisation of the entropy of cellular
      structures, based on the compactivity concept for granular packings. Hamiltonian
      like volume functions are constructed both in two and in three dimensions,
      enabling the identification of a phase space and making it possible to take
      account of geometrical correlations systematically. Case studies are presented
      for which explicit calculations of the mean vertex density and porosity
      fluctuations are given as functions of compactivity. The formalism applies
      equally well to two- and three-dimensional granular assemblies.

PMID- 16446982
TI  - Size and viscoelasticity of spatially confined multilamellar vesicles.
AB  - We studied viscoelastic properties and scaling behavior of multilamellar vesicles
      (MLVs) confined between two parallel plates as a function of the shear rate and
      sample thickness (gap size between parallel plates). The rheological properties
      are classified into two regimes; the shear-thinning regime at high shear rates
      and the shear-thickening regime at low shear rates. In the former, the MLV radius
      results from the mechanical balance between the effective surface tension
      sigma(eff) and viscous stress force. The MLV radius is independent of the gap
      size. sigmaeff estimated by van der Linden model is 2.1+/-0.15x10(-4) Nm-1
      corresponding to the same value obtained by SANS measurement. Power law exponents
      for the steady state viscosity and yield stress against pre-shear rate ([see
      text], [see text]) well agree with prediction based on the layering of membranes.
      Therefore, viscoelastic properties in this regime could be modeled by assuming
      that the dynamics of MLVs are driven by layering of MLV polydomains, which could
      be accompanied by the viscous dissipation, i.e., the stress relaxation on the
      MLV, induced by continuous sequence of yields of MLVs. The flow curve is
      empirically explained by the assumption of a relaxation time for the MLV shape.
      In the latter, however, scaling laws observed in the shear-thinning regime break
      down. The MLV radius increases when the gap size is reduced below the threshold
      value and MLV is no longer formed at very small gap sizes. Different dynamics
      from the shear-thinning regime seem to dominate the viscoelasticity.

PMID- 16446984
TI  - Motions induced by asymmetric vibrations. The solid/solid case.
AB  - We discuss theoretically the motions of a coin on a horizontally vibrating plate,
      with dry friction between the coin and the plate. As first noticed by Daniel and
      Chaudhury in a different situation (droplets on a plate), when the periodic
      acceleration gamma(t) imposed by the plate is unsymmetrical, the coin can move
      macroscopically with a certain drift velocity V. We analyse here: (a) the
      vibration threshold below which V=0, and the generic behavior expected just above
      threshold; (b) the limiting behavior at very high amplitudes, where V should
      become independent of the amplitude; (c) the complications due to small,
      macroscopic inhomogeneities on the supporting plate.

PMID- 16446985
TI  - The "macromolecular tourist": universal temperature dependence of thermal
      diffusion in aqueous colloidal suspensions.
AB  - By performing measurements on a large class of macromolecular and colloidal
      systems, we show that thermophoresis (particle drift induced by thermal
      gradients) in aqueous solvents displays a distinctive universal dependence on
      temperature. For systems of particles interacting via temperature-independent
      forces, this behavior is strictly related to the solvent thermal expansivity,
      while an additional, T-independent term is needed to account for the behavior of
      "thermophilic" (migrating to the warmth) particles. The former relation between
      thermophoresis and thermal expansion may be exploited to envisage other fruitful
      studies of colloidal diffusion in inhomogeneous fluids.

PMID- 16446986
TI  - A phase II study of chloroquinoxaline sulfonamide (CQS) in patients with
      metastatic colorectal carcinoma (MCRC).
AB  - PURPOSE: Phase II multicenter study investigated the efficacy and toxicity of the
      novel halogenated derivative of sulfaquixonaline Chloroquinoxaline Sulfonamide
      (CQS) in metastatic colorectal cancer. EXPERIMENTAL DESIGN: Eligible patients
      with metastatic or recurrent colorectal cancer received CQS at a dose schedule of
      2000 mg/m2 over an hour weekly for 4 weeks every 42 days. Treatment was continued
      until unexpected toxicity or disease progression. RESULTS: A total of seventeen
      patients were enrolled on this study. 94% of all patients enrolled had prior
      treatment. Sixteen patients were evaluable for response with fifteen patients
      showing evidence of disease progression and one patient with prolonged stable
      disease. One patient had non-evaluable disease. Following this interim analysis,
      the drug was considered ineffective and the study was terminated early. The most
      frequent adverse event was anemia. No patients discontinued the treatment because
      of toxicity. CONCLUSION: CQS, when given at a dose of 2000 mg/m2 weekly for 4
      weeks every 42 days to patients with metastatic colorectal cancer, does not
      result in significant tumor regression.

PMID- 16446987
TI  - Self-appraisal hierarchical task analysis of laparoscopic surgery performed by
      expert surgeons.
AB  - BACKGROUND: Evaluation of technical skill is notoriously difficult because of the
      subjectivity and time-consuming expert analysis. No ongoing evaluation scheme
      exists to assess the continuing competency of surgeons. This study examined
      whether surgeons' self-assessment accurately reflects their actual surgical
      technique. METHODS: Hierarchical task analysis (HTA) of laparoscopic
      cholecystectomy was constructed. Ten expert surgeons were asked to modify the HTA
      for their own technique. The HTAs of these surgeons then were compared with their
      actual operations, which had been recorded and assessed by two observers.
      RESULTS: A total of 40 operations were assessed. All the gallbladders subjected
      to surgery were classified as grades 1 to 3. The mean interrater reliability for
      the two observers had a k value of 0.84 (p < 0.05), and the mean intrarater
      reliability between surgeons and observers had a k value of 0.79 (p < 0.05).
      CONCLUSIONS: Surgeons' self-evaluation is accurate for technical skills aspects
      of their operations. This study demonstrates that self-appraisal using HTA is
      feasible, accurate, and practical. The authors aim to increase the numbers in
      their study and also to recruit residents.

PMID- 16446988
TI  - Endoscopic ultrasonography for gastric cancer: does it influence treatment?
AB  - BACKGROUND: This study aimed to evaluate the utility and shortcomings of
      endoscopic ultrasound (EUS) in tumor node metastasis (TNM) staging of gastric
      cancer and its influence on treatment. METHODS: The series included 126 patients
      (65 men and 44 women) with gastric cancer who underwent EUS from July 1997 to
      June 2003 at the National University Hospital, Singapore. The final analysis
      included 109 patients ranging in age from 29 to 97 years (mean, 63.13 years).
      RESULTS: EUS staging for primary disease: Specimen histology was available for
      102 of the 109 patients who underwent surgery. The accuracy was 79% for T1, 73.9%
      for T2, 85.7% for T3, and 72.7% for T4. The overall accuracy was 80.4%. EUS
      staging for nodes: The sensitivity of EUS for detecting nodal disease was 74.2%
      for N0, 78% for N1, 53.8% for N2, and 50% for N3. Overall, the N staging by EUS
      showed a sensitivity of 82.8%, a specificity of 74.2%, a positive predictive
      value of 85.4%, a negative predictive value of 70.2%, and an accuracy of 77.7%.
      Radical gastrectomy was proposed for 95 patients on the basis of the staging with
      EUS and computed tomography (CT) scan, and 87 patients (91.6%) underwent the
      surgery. Preoperative staging accurately predicted the operative strategy for 89%
      of the patients. No significant predictor for accuracy was achieved by performing
      a logistic regression analysis for the correct staging of T stage using EUS and
      adjusting for tumor location (middle part/distal third/whole stomach vs
      proximal/cardioesophageal) (p = 0.873), operator (p = 0.546), and subject's
      sequence (initial 50 vs last 50 cases) (p = 0.06). CONCLUSION: Ultrasound is the
      most accurate and reliable method for the preoperative staging of gastric
      carcinomas, and it is mandatory if a tailored therapeutic approach is planned
      according to stage.

PMID- 16446990
TI  - Phosphorus amendment reduces hematological effects of lead in mallards ingesting
      contaminated sediments.
AB  - Lead poisoning of waterfowl has been reported for decades in the Coeur d'Alene
      River Basin (CDARB) in Idaho as a result of the ingestion of lead-contaminated
      sediments. This study was conducted to determine whether the addition of
      phosphoric acid to sediments would reduce the bioavailability and toxicity of
      lead to mallards (Anas platyrhynchos) as related to adverse hematological effects
      and altered plasma chemistries. Mallards received diets containing 12% clean
      sediment (controls) or 12% sediment from three different CDARB sites containing
      4520, 5390, or 6990 microg/g lead (dw) with or without phosphoric acid amendment.
      Blood lead concentrations were significantly higher in all CDARB treatment groups
      and ranged from geometric mean values of 5.0 microg/g for the first two sites to
      6.2 microg/g for the third site. With amendments, all blood lead concentrations
      became 41% to 64% lower. Red blood cell ALAD activity was depressed by 90% or
      more with lead-contaminated sediment from all sites and did not differ with
      amended diets. Free erythrocyte protoporphyrin (FEP) concentrations were elevated
      by contaminated sediment from all sites. Amendment decreased the elevations in
      FEP by as much as 80%. Hematocrit values and hemoglobin concentrations were lower
      for all lead site sediments by as much as 30% for site 3. Plasma enzyme
      activities for ALT, CK, and LDH-L were elevated by as much as 2.2-fold, and
      plasma creatinine concentration was 1.7-fold higher for site 3 sediment.
      Amendments restored hematocrit, hemoglobin, and plasma enzyme activities so that
      they did not differ from controls. Although amendments of phosphorus
      substantially reduced the bioavailability of lead and alleviated many of the
      adverse hematological effects, lead concentrations in the blood of mallards fed
      the amended sediments were still above those believed to be harmful to waterfowl
      under the present conditions.

PMID- 16446989
TI  - Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging.
AB  - BACKGROUND: Replication-competent, tumor specific herpes simplex virus NV1066
      expresses green fluorescent protein (GFP) in infected cancer cells. We sought to
      determine the feasibility of GFP-guided imaging technology in the intraoperative
      detection of small tumor nodules. METHODS: Human cancer cell lines were infected
      with NV1066 at multiplicities of infection of 0.01, 0.1 and 1. Cancer cell
      specific infectivity, vector spread and GFP signal intensity were measured by
      flow cytometry and time-lapse digital imaging (in vitro); and by use of a
      stereomicroscope and endoscope equipped with a fluorescent filter (in vivo).
      RESULTS: NV1066 infected all cancer cell lines and expressed GFP at all MOIs. GFP
      signal was significantly higher than the autofluorescence of normal cells. One
      single dose of NV1066 spread within and across body cavities and selectively
      infected tumor nodules sparing normal tissue. Tumor nodules undetectable by
      conventional thoracoscopy and laparoscopy were identified by GFP fluorescence.
      CONCLUSION: Virally-directed fluorescent imaging (VFI) is a real-time novel
      molecular imaging technology that has the potential to enhance the intraoperative
      detection of endoluminal or endocavitary tumor nodules.

PMID- 16446991
TI  - Selenium and other trace elements in aquatic insects in coal mine-affected
      streams in the Rocky Mountains of Alberta, Canada.
AB  - We determined levels of Se, As, Cd, Pb, and Zn in aquatic insects at coal mine
      impacted and reference sites in streams in the Rocky Mountain foothills of west
      central Alberta from 2001-2003. Selenium levels were greater at coal mine
      impacted sites than at reference sites in caddisflies but not in mayflies or
      stoneflies. Arsenic levels were greater at coal mine-impacted sites than at
      reference sites in caddisflies and stoneflies but not in mayflies. Zn levels were
      higher at coal mine-impacted sites than at reference sites in all three groups of
      insects. At coal mine-impacted sites, Se levels in mayflies and caddisflies were
      greater than those in stoneflies while at reference sites mayflies contained
      greater concentrations of Se than either caddisflies or stoneflies. Arsenic
      levels in mayflies were greater than those in caddisflies at reference and coal
      mine-impacted sites and were greater than those in stoneflies at reference sites.
      At both types of sites Cd differed amongst insect taxa in the order of mayflies >
      caddisflies > stoneflies. The same was true of Zn at coal mine-affected sites. At
      reference sites, stoneflies had greater concentrations of Zn than both mayflies
      and caddisflies. At both types of sites, Pb levels were greater in mayflies and
      caddisflies than they were in stoneflies. Of the five trace elements considered
      in this study, only Se was sufficiently elevated in aquatic invertebrates to be
      of potential concern for consumers such as fish and aquatic birds. Such was the
      case at both coal mine-impacted and reference sites.

PMID- 16446992
TI  - Composition, distribution, and characterization of suspected endocrine-disrupting
      pesticides in Beijing GuanTing Reservoir (GTR).
AB  - GuanTing Reservoir (GTR) is one of two main water resources for the agriculture,
      industry, and living uses of Beijing (China). As a result of extensive pollution
      over the last few decades (particularly the 1980s), the reservoir has not
      supplied potable water to Beijing city since 1997. Composition, distribution, and
      characterization of 31 suspected endocrine-disrupting pesticides in surface
      water, pore water, and surface sediments from the reservoir are reported in this
      study. An analytical procedure based on solid-phase extraction (SPE) technology
      and capillary gas chromatography with electron-capture detection has been
      developed for the simultaneous determination of the 31 suspected endocrine
      disrupting pesticides including the compounds hexachlorocyclohexane, cyclodiene,
      diphenyl aliphatic, chlordane, and other selected pesticides (hexachlorobenzene,
      heptachlor, endrin aldehyde, hepachlor epoxide, dicofol, acetochlor, alachlor,
      metolachlor, chlorpyriphos, nitrofen, trifluralin, cypermethrin, fenvalerate, and
      deltamethrin). The result shows that the pesticide pollution is moderate in GTR
      and its tributaries, although pesticide residue values in a few sites are quite
      high when considering their endocrine-disrupting effects and chronic health
      effects. Among the analyzed pesticides, p,p'-DDE, o,p'-DDT, beta-HCH, endosulfan
      sulfate, and aldrin were the most abundant pesticides in water while o,p'-DOT,
      delta-HCH, beta-HCH, p,p'-DDE, p,p'-DDT, and endosulfan sulfate were the most
      abundant in sediment. The variation in concentration of pesticides among sites
      can be expected to be caused by several factors such as contaminants in the
      rivers and drainage of contaminated water from the surrounding agricultural
      fields. To reduce exposure to these endocrine-disrupting compounds, the abundant
      current use of pesticides in the area should be minimized. Regular monitoring is
      needed to manage the environmental hazards due to these pesticides.

PMID- 16446993
TI  - Interactive alterations of arsenic and malathion in the disposition kinetics of
      pefloxacin.
AB  - Assessment of deleterious effects produced by concurrent exposure to commonly
      encountered chemicals is of great concern to find out toxicological consequences
      arising as a result of their interactions and for a more comprehensive management
      of chemical-induced untoward effects. The naturally occurring heavy metal arsenic
      is present in food and water. Malathion is one of the most widely used pesticides
      in agriculture and public health practices worldwide. Humans, animals, and birds
      are exposed to these chemicals through environmental processes. Since arsenic and
      malathion are shown to exert an inhibitory effect on cytochrome P450 activities,
      their continuous exposure may alter the disposition kinetics of drugs that are
      predominantly metabolized hepatically. The current study was undertaken to
      evaluate the impact of subchronic exposure of arsenic, malathion, and their
      combination on the disposition kinetics of widely used fluoroquinolone
      antimicrobial pefloxacin in chickens. Broiler chickens were exposed to either
      arsenic (50 ppm), malathion (500 ppm), or arsenic (50 ppm) plus malathion (500
      ppm). Arsenic and malathion were given in drinking water and feed, respectively.
      Following 28 days of exposure, all birds received a single oral dose of
      pefloxacin (10 mg/kg) and the plasma concentrations and the disposition kinetic
      parameters of the drug were determined. In the birds not exposed to arsenic
      and/or malathion, the elimination half-life (t(1/2beta)), area under the plasma
      concentration-time curve (AUC), maximum plasma drug concentration (C(max)), mean
      residence time (MRT), and bioavailability of pefloxacin were 8.46 +/- 0.24 h,
      39.06 +/- 1.13 microg.h.ml(-1), 2.69 +/- 0.19 microg.ml(-1), 12.29 +/- 0.48 h,
      and 60.52 +/- 1.74%, respectively. Exposure to arsenic was associated with a
      significant increase in C(max) (4.28 +/- 0.45 microg.ml(-1)) and a nonsignificant
      increase in the values of AUC (48.96 +/- 2.55 microg.h.ml(-1)) and
      bioavailability (74.55 +/- 3.8 %) of pefloxacin. The values of AUC (51.62 +/-
      4.76 microg.h.ml(-1)), t(1/2beta) (12.57 +/- 1.26 h), MRT (19.94 +/- 1.99 h), and
      bioavailability (78.59 +/- 7.25 %) of pefloxacin were significantly increased in
      malathion-exposed birds. Concomitant exposure to arsenic and malathion did not
      affect the disposition kinetic variables of pefloxacin. The study shows that
      subchronic malathion exposure significantly alters the elimination kinetics of
      pefloxacin. Following concurrent exposure, arsenic nullifies the malathion
      induced changes in disposition kinetics of pefloxacin by possibly diminishing the
      cytochrome P450-catalyzed bioactivation of malathion.

PMID- 16446994
TI  - Anal fin morphology and gonadal histopathology in mosquitofish (Gambusia
      holbrooki) exposed to treated municipal sewage effluent.
AB  - Feral mosquitofish living in undiluted treated municipal sewage in Queensland,
      Australia, were examined for morphologic abnormalities indicative of reproductive
      dysfunction. Male and female mosquitofish were captured at two sites receiving
      undiluted treated sewage and compared with those captured at a reference site.
      Several morphologic end points were examined, including length of the fourth and
      sixth anal fin rays and gonadal histology. Both male and female mosquitofish at
      one site exhibited minor elongation of the fourth anal fin ray consistent with
      exposure to androgenic stimulation, although the spatial extent of the effect was
      limited and not significant at other sites further downstream. No incidences of
      intersex were found. These findings suggest that the level of treatment of
      domestic sewage at the two sewage treatment plants assessed is adequate to
      prevent reproductive abnormalities in exposed mosquitofish populations.

PMID- 16446995
TI  - Persistent organochlorine contaminants in liver and fat of birds of prey from
      Greece.
AB  - The concentrations of persistent organic pollutants, such as DDT and its
      metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), cyclodienes (Cycls),
      and polychlorinated biphenyls (PCBs), were measured in livers and subcutaneous
      fat tissues of six Accipitridae and four Falconidae bird species from different
      areas in Greece. This is the first report of persistent organochlorine (OC)
      pollutants in birds of prey tissues presented for Greece and the Eastern
      Mediterranean region. Accumulation patterns of OCs found in birds suggested that
      the predominant contaminants were p,p'-dichlorodiphenyldichloro-1,1-ethylene
      (DDE) and PCBs, whereas Cycls and HCHs occurred at low concentrations only.
      Concentration values of p,p'-DDE ranged from nondetected to 19,518.72 ng/g wet wt
      in livers and from nondetected to 2679.19 ng/g wet wt in fat. Total PCB levels
      ranged from 1.01 to 7419.43 ng/g and from 3.25 to 490.10 ng/g wet weight for
      liver and fat samples, respectively. Higher-chlorinated PCBs such as 118, 138,
      153, and 180 predominated in both the liver and subcutaneous fat samples, a
      pattern comparable to that observed in birds from other European countries. No
      significant differences in mean concentrations of OCs are detected between
      species. Hepatic concentrations were in general higher than the fat
      concentrations showing depleted fat stores in most birds. Concentration ranges
      were also found in lower or similar levels to those reported for birds in other
      regions. Variation of OCs levels in bird tissues could be due to different causes
      of death, with a subsequent effect on body lipid levels, and different feeding
      and migration habits. The liver PCB levels reported in this study are below the
      concentrations currently believed to exert mortality or ecotoxicological effects.
      On the contrary, in some cases p,p'-DDE concentrations were higher than the
      reported effect values for birds of the same families and could be associated
      with sublethal effects.

PMID- 16446996
TI  - Serum protein profile and blood cell counts in adult toads Bufo
      arenarum(Amphibia: Anura: Bufonidae): effects of sublethal lead acetate.
AB  - Lead is a multiple-source pollutant, well known for its toxicity, of great risk
      both for the environment and human health. The main target organs of lead are the
      hematopoietic, nervous, and renal systems; there are also reports in support of
      its impairment effects on the reproductive and immune systems. It is well known
      that most of the metal is accumulated in the blood cells and that many of the
      deleterious effects are related to its circulating concentrations. These adverse
      effects have been described not only in humans but also in a number of other
      vertebrates such as fish and birds. The purpose of the present work was to
      evaluate the effects of weekly administration of sublethal Pb (as acetate, 50 mg
      x kg(-1)) during 6 weeks on the profile of the serum proteins and blood cell
      counts of the adult South American toad, Bufo arenarum (Anura: Bufonidae). The
      electrophoretic patterns of serum proteins pointed out the presence of four
      fractions; the metal provoked a significant decrease in both total proteins and
      albumin fraction; among the globulin fractions, the G3 resulted augmented. These
      findings may be related to the impact of lead on the toads' hepatic cells and
      immune system. The number of total red blood cells (RBC) showed a tendency to
      decrease after the injections of the metal, whereas the number of white blood
      cells (WBC) increased significantly; the differential leukocyte counts showed a
      statistically significant increase in the absolute number and in the relative
      percentage of blast-like cells. The decrease in RBC was attributed to the
      negative impact of the metals on the hemoglobin synthesis. The increasing of the
      WBC counts may be interpreted as a consequence of the induction of proliferation
      of pluripotential hematopoietic cells.

PMID- 16446997
TI  - Nitrile glove permeation of benomyl.
AB  - The aim of this study was to investigate permeation of the fungicide benomyl at
      its highest field application concentration (0.70 mg/mL) in Benlate 50 WP aqueous
      solution (1.4 mg/mL) through two types of unsupported and unlined nitrile gloves-
      a disposable latex glove (Safeskin) and an industrial chemical-resistant glove
      (Solvex)--using an American Society for Testing and Materials (ATSM)-type
      permeation cell with isopropanol collection medium. The permeation cell was
      contained in a moving-tray water bath at 30.0 degrees C +/- 0.5 degrees C. The
      collection medium was evaporated and the residue derivatized with an optimized
      method (2,3,4,5,6-pentafluoro)benzyl bromide to form the disubstituted derivative
      of carbendazim (CARB), CARB.2PFB. The latter in isooctane was then quantified by
      gas chromatography- 63Ni-electron capture detection (GC-ECD) by the internal
      standard method. GC-ECD, GC-mass spectrometry (GC-MS), and reflectance infrared
      investigations showed that little degradation of benomyl occurred in the
      challenge solution of aqueous Benlate during an 8-hour exposure period. Benomyl
      was collected as a mixture of CARB and benomyl as shown by the presence of a
      diagnostic chromatographic peak identified by GC-MS. The amounts permeated during
      the same time period were always higher for Safeskin than for Solvex gloves, with
      the latter being approximately 18 times more protective than the former after 8
      hours of continuous exposure. Although the Solvex gloves were safe to wear at
      least for 4 hours and for almost 8 hours, the ASTM breakthrough threshold was
      used as reference and thus ignored carcinogenic effects. Reflectance infrared
      investigations detected benomyl and CARB on the glove challenge surface after
      drying and confirmed that the cleaned glove surfaces after permeation experiments
      did not differ in infrared reflectance spectra from the corresponding surfaces
      just before the permeation experiments.

PMID- 16446998
TI  - Toxic effects of irgarol and diuron on sea urchin Paracentrotus lividus early
      development, fertilization, and offspring quality.
AB  - Irgarol and Diuron are the most representative "organic booster biocides" that
      replaced organotin compounds in antifouling paints. It cannot be assumed
      beforehand that their use will have no environmental impact: more
      ecotoxicological data and a significant environmental monitoring are required.
      Spermio and embryotoxicities of the biocides Irgarol and Diuron were investigated
      on Paracentrotus lividus, the dominant echinoid species of the Mediterranean Sea.
      Spermiotoxicity was studied by assessing the effects of sperm exposure on
      fertilization rate as well as on the induction of transmissible damages to the
      offspring. Embryotoxicity was studied by assessing the developmental defects in
      the exposed larvae. The experimental results show a Diuron EC50 of 2.39 (+/-
      0.21) mg/L with a NOEL of 0.25 mg/L for embryos, and of 5.09 (+/- 0.45) mg/L with
      a NOEL of 0.5 mg/L for sperms, respectively. Data obtained from the
      embryotoxicity test on Irgarol [EC50 0.99 (+/- 0.69) mg/L] are of the same order
      of magnitude as the literature data about Japanese urchins. Spermiotoxicity tests
      show an Irgarol EC50 of 9.04 (+/- 0.45) mg/L with a NOEL of 0.1 mg/L. These data
      show the different sensitivities of the two tests: embryos are more sensitive
      than sperms for both the tested chemicals and Diuron seems to be the less toxic
      one. Moreover, as a major output of the experimental work, tested herbicides
      exert transmissible damage to spermatozoa evidenced by larval malformations in
      the offspring, mainly P1 type (skeletal alterations). The comparison of the
      endpoints results offers an interesting indication of a probable different mode
      of action (Irgarol seems to interact with calcium homeostasis) of the two
      biocides.

PMID- 16447000
TI  - Emergency endovascular treatment of abdominal aortic aneurysms: feasibility and
      results.
AB  - PURPOSE: To assess the feasibility and effectiveness of emergency endovascular
      treatment of abdominal aortic aneurysms (AAAs). METHODS: During 36 months we
      treated, on an emergency basis, 30 AAAs with endovascular exclusion. In 21
      hemodynamically stable patients preoperative CT angiography (CTA) was performed
      to confirm the diagnosis and to plan the treatment; 9 patients with hemorrhagic
      shock were evaluated with angiography performed in the operating room. Twenty-two
      Excluder (Gore) and 8 Zenith (Cook) stent-grafts (25 bifurcated and 5 aorto-uni
      iliac) were used. The follow-up was performed by CTA at 1, 3, 6, and 12 months.
      RESULTS: Technical success was achieved in 100% of cases with a 10% mortality
      rate. The total complication rate was 23% (5 increases in serum creatinine level
      and 2 wound infections). During the follow-up, performed in 27 patients (1-36
      months, mean 15.2 months), 4 secondary endoleaks (15%) (3 type II, 2
      spontaneously thrombosed and 1 under observation, and 1 type III treated by iliac
      extender insertion) and 1 iliac leg occlusion (treated with femoro-femoral
      bypass) occurred. We observed a shrinkage of the aneurysmal sac in 8 of 27 cases
      and stability in 19 of 27 cases; we did not observe any endotension. CONCLUSIONS:
      Endovascular repair is a good option for emergency treatment of AAAs. The team's
      experience allows correct planning of the procedure in emergency situations also,
      with technical results comparable with elective repair. In our experience the
      bifurcated stent-graft is the device of choice in patients with suitable anatomy
      because the procedure is less time-consuming than aorto-uni-iliac stent-grafting
      with surgical crossover, allowing faster aneurysm exclusion. However, further
      studies are required to demonstrate the long-term efficacy of endovascular repair
      compared with surgical treatment.

PMID- 16446999
TI  - Mercury concentrations in gonad, liver, and muscle of white sturgeon Acipenser
      transmontanus in the lower Columbia River.
AB  - This study determined the partitioning of total mercury in liver, gonad, and
      cheek muscle of white sturgeon (Acipenser transmonatus) in the lower Columbia
      River. The relationship between tissue mercury concentrations and various
      physiologic parameters was assessed. White sturgeon were captured in commercial
      fisheries in the estuary and Bonneville, The Dalles, and John Day Reservoirs.
      Condition factor (CF), relative weight (Wr), and gonadosomatic index (GSI) were
      determined for each fish (n = 57). Gonadal tissue was examined histologically to
      determine sex and stage of maturity. Liver (n = 49), gonad (n = 49), and cheek
      muscle (n = 57) were analyzed for total mercury using cold-vapor atomic
      fluorescence spectrophotometry. Tissue protein concentrations were measured by
      ultraviolet-visible spectroscopy. Plasma was analyzed for testosterone (T), 11
      ketotestosterone (KT), and 17ss-estradiol (E2) using radioimmunoassay. Mean
      tissue mercury concentrations were higher in muscle compared with liver and gonad
      at all sampling locations, except Bonneville Reservoir where mean liver mercury
      content was the highest tissue concentration observed in the study. Significant
      negative correlations between plasma androgens (T and KT) and muscle mercury
      content and plasma E2 and liver mercury content were found. A significant
      positive linear relationship between white sturgeon age and liver mercury
      concentrations was evident. Significant negative correlations between CF and
      relative weight and gonad and liver mercury content were found. In addition,
      immature male sturgeon with increased gonad mercury content had decreased GSIs.
      These results suggest that mercury, in the form of methylmercury, may have an
      effect on the reproductive potential of white sturgeon.

PMID- 16447001
TI  - Renal tumors: technical success and early clinical experience with radiofrequency
      ablation of 18 tumors.
AB  - PURPOSE: To evaluate the feasibility, safety, and technical efficacy of image
      guided radiofrequency ablation (RFA) for the treatment of small peripheral renal
      tumors and to report our early results with this treatment modality. METHODS:
      Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal
      tumors. Indications included coexistent morbidity, high surgical or anesthetic
      risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten
      patients had CT-guided percutaneous RFA performed on an outpatient basis. One
      patient had open intraoperative ultrasound-guided RFA. Technical success was
      defined as elimination of areas that enhanced at imaging within the entire tumor.
      With the exception of one patient with renal insufficiency who required
      gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT
      for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks
      and then at 3, 6, 12 months, and every 12 months thereafter. RESULTS: Fourteen
      (78%) of 18 tumors were successfully ablated with one session. Three of the
      remaining four tumors required two sessions for successful ablation. One tumor
      will require a third session for areas of persistent enhancement. Mean patient
      age was 72.82 +/- 10.43 years. Mean tumor size was 1.95 +/- 0.79 cm. Mean follow
      up time was 10.91 months. All procedures were performed without any major
      complications. CONCLUSIONS: Our early experience with percutaneous image-guided
      radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and
      effective treatment of small peripheral renal tumors.

PMID- 16447002
TI  - Pain and return to daily activities after uterine artery embolization and
      hysterectomy in the treatment of symptomatic uterine fibroids: results from the
      randomized EMMY trial.
AB  - PURPOSE: To evaluate the safety and efficacy of uterine artery embolization (UAE)
      and hysterectomy for symptomatic uterine fibroids by means of a randomized
      controlled trial. The present paper analyses short-term outcomes, i.e., pain and
      return to daily activities. METHODS: Patients were randomized (1:1) to UAE or
      hysterectomy. Pain was assessed during admission and after discharge, both
      quantitatively and qualitatively, using a numerical rating scale and
      questionnaires. Time to return to daily activities was assessed by questionnaire.
      RESULTS: Seventy-five patients underwent hysterectomy and 81 patients underwent
      UAE. UAE patients experienced significantly less pain during the first 24 hr
      after treatment (p = 0.012). Non-white patients had significantly higher pain
      scores. UAE patients returned significantly sooner to daily activities than
      hysterectomy patients (for paid work: 28.1 versus 63.4 days; p < 0.001). In
      conclusion, pain appears to be less after UAE during hospital stay. Return to
      several daily activities was in favor of UAE in comparison with hysterectomy.

PMID- 16447003
TI  - Nonoperable recurrent renal cell carcinoma: management with embolization and CT
      guided RF ablation.
AB  - We report the case of a 59-year-old male who underwent embolization and computed
      tomography-guided radiofrequency ablation of a recurrent renal cell carcinoma
      that developed after radical nephrectomy in contiguity to the inferior vena cava.
      The alternative of a new operation was rejected because of the proximity of the
      tumor to the vessel and percutaneous approach seemed to be the better solution.

PMID- 16447004
TI  - Recurrent congenital diaphragmatic hernia in Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome (EDS) includes a group of connective tissue disorders with
      abnormal collagen metabolism and a diverse clinical spectrum. We report two
      siblings with EDS who both presented with congenital diaphragmatic hernia (CDH).
      The elder sister suffered from recurrent diaphragmatic hernia twice and EDS was
      overlooked initially. Echocardiography as well as contrast-enhanced magnetic
      resonance angiography (MRA) showed dilatation of the pulmonary artery, and marked
      elongation and tortuosity of the aorta and its branches. A diagnosis of EDS was
      eventually established when these findings were coupled with the clinical
      features of hyperelastic skin. Her younger brother also had similar features.
      This report emphasizes that EDS may present as CDH in a small child which could
      easily be overlooked. Without appropriate surgery, diaphragmatic hernia might
      occur. Echocardiographic screening is recommended in patients with CDH. Contrast
      enhanced MRA can be helpful in delineation of abnormally tortuous aortic great
      vessels that are an important clue to the early diagnosis of EDS.

PMID- 16447005
TI  - Placement of an inferior vena cava filter in a patient with azygos continuation
      complicated by pulmonary embolism.

PMID- 16447006
TI  - Endovascular treatment of traumatic aneurysm of the occipital artery.

PMID- 16447007
TI  - Percutaneous transhepatic use of a cutting balloon in the treatment of a benign
      common bile duct stricture.
AB  - Benign biliary strictures (BBS) are difficult to treat. The majority of them are
      treated either endoscopically or using percutaneous techniques either with stents
      or conventional angioplasty balloons. To our knowledge we present the first case
      of use of a cutting balloon in the treatment of BBS through a percutaneous
      approach.

PMID- 16447008
TI  - Osteoid osteoma: experience with laser- and radiofrequency-induced ablation.
AB  - The purpose of this study was to analyze the clinical outcome of osteoid osteoma
      treated by thermal ablation after drill opening. A total of 17 patients and 20
      procedures were included. All patients had typical clinical features (age, pain)
      and a typical radiograph showing a nidus. In 5 cases, additional histological
      specimens were acquired. After drill opening of the osteoid osteoma nidus, 12
      thermal ablations were induced by laser interstitial thermal therapy (LITT) (9F
      Power-Laser-Set; Somatex, Germany) and 8 ablations by radiofrequency ablation
      (RFA) (RITA; StarBurst, USA). Initial clinical success with pain relief has been
      achieved in all patients after the first ablation. Three patients had an osteoid
      osteoma recurrence after 3, 9, and 10 months and were successfully re-treated by
      thermal ablation. No major complication and one minor complication (sensible
      defect) were recorded. Thermal ablation is a safe and minimally invasive therapy
      option for osteoid osteoma. Although the groups are too small for a comparative
      analysis, we determined no difference between laser- and radiofrequency-induced
      ablation in clinical outcome after ablation.

PMID- 16447010
TI  - Assessment of osteoporosis-website quality.
AB  - INTRODUCTION: The Internet provides great opportunities for patient healthcare
      education, but poses risks that inaccurate, outdated, or harmful information will
      be disseminated. Osteoporosis is a topic of great interest to patients, many of
      whom use the Internet to obtain medical information. The aim of this study was to
      develop and evaluate measurement tools to determine the quality of osteoporosis
      websites for patients. METHODS: Quality indicators in the categories of content,
      credibility, navigability, currency, and readability were incorporated into
      separate evaluation tools for healthcare professionals and for patients. Websites
      were selected from an Internet search. Interobserver reliability and validity
      were assessed, and a sample of osteoporosis websites was evaluated by an
      osteoporosis nurse educator and compared to patient evaluations. RESULTS: For the
      quality indicators, there was 79% agreement between the osteoporosis nurse
      educators, 88% agreement between the physician osteoporosis experts, and 71%
      agreement comparing the osteoporosis nurse educators to the physician
      osteoporosis experts. Quality scores for evaluated websites ranged from 18-96
      (maximum possible=100), with a mean of 66. Websites with Uniform Resource Locator
      (URL) suffix .com scored significantly lower compared to those with .gov
      (P<0.05), .edu (P<0.01), and .org (P<0.01). Healthcare professionals and patients
      were in agreement on the quality of the highest-rated websites, with less
      agreement for lower-rated websites. CONCLUSIONS: In summary, a tool for measuring
      the quality of medical websites was developed and evaluated. Significant
      variability in osteoporosis-website quality was observed. Higher-quality scores
      were associated with a higher level of search engine match and specific URL
      suffixes. A validated tool for evaluating medical websites may have value in
      assisting patients to select high-quality osteoporosis educational information on
      the Internet, and may encourage website developers to improve the quality of
      information that is provided.

PMID- 16447009
TI  - Femur strength index predicts hip fracture independent of bone density and hip
      axis length.
AB  - INTRODUCTION: Proximal femoral bone strength is not only a function of femoral
      bone mineral density (BMD), but also a function of the spatial distribution of
      bone mass intrinsic in structural geometric properties such as diameter, area,
      length, and angle of the femoral neck. Recent advancements in bone density
      measurement include software that can automatically calculate a variety of
      femoral structural variables that may be related to hip fracture risk. The
      purpose of this study was to compare femoral bone density, structure, and
      strength assessments obtained from dual-energy X-ray absorbtiometry (DXA)
      measurements in a group of women with and without hip fracture. METHODS: DXA
      measurements of the proximal femur were obtained from 2,506 women 50 years of age
      or older, 365 with prior hip fracture and 2,141 controls. In addition to the
      conventional densitometry measurements, structural variables were determined
      using the Hip Strength Analysis program, including hip axis length (HAL), cross
      sectional moment of inertia (CSMI), and the femur strength index (FSI) calculated
      as the ratio of estimated compressive yield strength of the femoral neck to the
      expected compressive stress of a fall on the greater trochanter. RESULTS: Femoral
      neck BMD was significantly lower and HAL significantly higher in the fracture
      group compared with controls. Mean CSMI was not significantly different between
      fracture patients and controls after adjustment for BMD and HAL. FSI, after
      adjustment for T score and HAL, was significantly lower in the fracture group,
      consistent with a reduced capacity to withstand a fall without fracturing a hip.
      CONCLUSION: We conclude that BMD, HAL, and FSI are significant independent
      predictors of hip fracture.

PMID- 16447013
TI  - Radiotherapy for bony manifestations of Langerhans cell histiocytosis. Review and
      proposal for an international registry.
AB  - PURPOSE: To examine the role of radiotherapy (RT) in adult Langerhans cell
      histiocytosis (LCH) for osseous manifestations, to define open questions
      regarding RT, and to develop recommendations for the clinical decision-making and
      problem-solving process. MATERIAL AND METHODS: A literature review using
      different medical databases was conducted including the last 3 decades, and
      resulting questions regarding the use of ionizing radiation were systematically
      compiled. RESULTS: The literature review revealed a local control rate of 96%
      (93% complete remissions) in patients with osseous single-system disease and of
      92% (76% complete remissions) in patients with bony involvement in multi-system
      disease. To increase our knowledge, a prospective registry has been developed to
      allow a differentiated analysis of RT outcome and definition of potential
      prognostic factors. CONCLUSION: Ionizing radiation can be successfully applied as
      a single treatment or in combination with other therapies for osseous
      manifestations of LCH. It leads to high remission and local control rates.
      Nevertheless, many open questions still exist. A prospective clinical registry is
      proposed to define the exact role of RT in this disease and to develop future
      interdisciplinary treatment guidelines.

PMID- 16447012
TI  - Impact of hemoglobin levels on tumor oxygenation: the higher, the better?
AB  - BACKGROUND AND PURPOSE: Tumor hypoxia has been linked to tumor progression, the
      development of treatment resistance, and thus poor prognosis. Since anemia is a
      major factor causing tumor hypoxia, the association between blood hemoglobin
      concentration (cHb) and tumor oxygenation status has been examined. PATIENTS AND
      METHODS: Published data on the relationship between pretreatment cHb values and
      tumor oxygenation (in terms of median pO(2) values, hypoxic fractions) have been
      summarized. Pretreatment O(2) tension measurements were performed in
      histologically proven experimental tumors, human breast cancers, squamous cell
      carcinomas of the head and neck, and cancers of the uterine cervix and of the
      vulva. In order to allow for a comparison between solid tumors and normal
      tissues, pO(2) measurements were also performed in healthy tissue in anemic and
      nonanemic patients. cHb was determined at the time of the pO(2) measurements.
      RESULTS: Based on current information from experimental and clinical studies
      there is increasing evidence that anemia is associated with a detrimental tumor
      oxygenation status. Increasing cHb values are correlated with significantly
      higher pO(2) values and lower hypoxic fractions. Maximum tumor oxygenation in
      squamous cell carcinomas is observed at normal (gender-specific) cHb values
      (approximately 14 g/dl in women and approximately 15 g/dl in men). Above this
      "optimal" Hb range, the oxygenation status tends to worsen again. In anemic
      patients, tumor oxygenation is compromised due to a decreased O(2) transport
      capacity of the blood. At the upper edge of the Hb scale, a substantial increase
      in the blood's viscous resistance to flow in "chaotic" tumor microvessels is
      thought to be mainly responsible for the observed restriction of O(2) supply.
      CONCLUSION: Review of relevant clinical data suggests that a maximum oxygenation
      status in solid tumors is to be expected in the range 12 g/dl < cHb < 14 g/dl for
      women and 13 g/dl < cHb < 15 g/dl for men. Considering the "optimal" cHb range
      with regard to tumor oxygenation, the concept of "the higher, the better" is
      therefore no longer valid. This finding has potentially far-reaching implications
      in the clinical setting (e. g., inappropriate erythropoietin treatment of
      nonanemic tumor patients).

PMID- 16447011
TI  - Community introduction of practice parameters for autistic spectrum disorders:
      Advancing early recognition.
AB  - OBJECTIVES: Within a strong interdisciplinary framework, improvement in the
      quality of care for children with autistic spectrum disorders through a 2 year
      implementation program of Practice Parameters, aimed principally at improving
      early detection and intervention. METHOD: We developed Practice Parameters (PPs)
      for Pervasive Developmental Disorders and circulated the PPs to all child and
      adolescent psychiatrists practicing in the region. RESULTS: PP development and
      parallel information strategies resulted in a significant decrease of 1.5 years
      in the mean-age-at-diagnosis. However, further analysis indicated that
      improvement was only transient. CONCLUSION: Despite the encouraging improvement
      in mean-age-at-diagnosis 2 years after PP implementation, other indicators showed
      a failure to maintain the improvements. A systematic screening program would be
      the most reliable method to reinforce the PPs.

PMID- 16447014
TI  - Interindividual variability of lymph drainages in patients with cervical cancer.
      Implication on irradiation planning.
AB  - BACKGROUND AND PURPOSE: Lymph node metastases and the number of positive lymph
      nodes are important prognostic factors for patients with cervical cancer. The
      most important route is the lateral drainage via the obturator to the internal
      and external iliac and common iliac area. The risk for common iliac lymph node
      metastases is increased in patients with positive pelvic or paraaortic lymph
      nodes. Positive common iliac lymph nodes are associated with a poorer prognosis
      than positive pelvic lymph nodes excluding common iliac group. For radiation
      planning in patients with cervical cancer, lymph node regions at high risk for
      metastases have to be encompassed. Usually, standard fields are used with the
      upper field border on the fourth/fifth lumbar vertebra. The authors evaluated
      whether standard fields are sufficient for encompassing the common iliac lymph
      nodes. PATIENTS AND METHODS: Pretreatment computed tomographic (CT) images of 42
      patients with cervical cancer were evaluated to locate the aortic bifurcation and
      the subsequent common iliac lymph drainage. Anatomy of the lymph drain was
      correlated with standard radiation portals. RESULTS: In 17/42 patients (40%) the
      aortic bifurcation lay superior to the upper field border. In an additional nine
      patients (21%) the bifurcation was located on the level of the upper field
      border. In 26/42 patients (62%) standard radiation fields encompassed the common
      iliac lymph nodes insufficiently. CONCLUSION: Common iliac lymph node metastases
      are found in up to 50% of patients with node-positive cervical cancer. The
      results of this study demonstrate an unsatisfactory coverage of the common iliac
      lymph drain by standard fields in most patients. Thus it is necessary to
      individualize the planning target volume and to include the whole common iliac
      vessels according to the patient's anatomy on radiation treatment planning CT in
      order to improve local control.

PMID- 16447015
TI  - Ultrasound-guided interstitial brachytherapy in the treatment of advanced vaginal
      recurrences from cervical and endometrial carcinoma.
AB  - BACKGROUND: In advanced vaginal recurrences of cervical and endometrial
      carcinomas therapeutic options are rare because of preceding therapy. PATIENTS
      AND METHODS: 23 patients developing advanced vaginal recurrences of cervical and
      endometrial carcinomas were included. 15 patients started with external-beam
      therapy to the pelvis and eight patients after preceding radiotherapy underwent
      brachytherapy alone. All patients had ultrasound-guided implantation of
      transvaginal or transperineal interstitial needles for brachytherapy. Median
      prescribed total dose was 64 Gy. RESULTS: 18 patients (78%) achieved complete
      remission. Six patients are alive without tumor and one with tumor after a median
      follow-up of 64 months. 14 patients died of tumor and two of intercurrent
      disease. 5-year disease-specific survival and local control rate were 43% and
      47%, respectively, in patients with complete remission. Univariate analysis found
      time to relapse > 2 years, initial diameter < or = 4 cm, initial volume < 15
      cm(3), no extension to the pelvic side wall, volume before brachytherapy < 7.5
      cm(3), brachytherapy coverage index > 0.8, and prescribed total dose > 64 Gy
      being positive predictors for local control and survival. CONCLUSION: The use of
      ultrasound guidance for placement of interstitial needles in template-based
      brachytherapy of advanced recurrent gynecologic malignancies is a feasible, safe,
      and cheap method with encouraging results. Today, ultrasound imaging can be also
      used to some extent for treatment planning which requires further development.
      Patient- and treatment-related prognostic factors can be defined.

PMID- 16447016
TI  - Comparison of CT- and radiograph-based post-implant dosimetry for transperineal
      125I prostate brachytherapy using single seeds and a commercial treatment
      planning software.
AB  - BACKGROUND AND PURPOSE: The objective of this investigation was a direct
      comparison of the dosimetry of CT-based and radiograph- based postplanning
      procedures for seed implants. PATIENTS AND METHODS: CT- and radiograph-based
      postplans were carried out for eight iodine-125 ((125)I) seed implant patients
      with a commercial treatment-planning system (TPS). To assess a direct comparison
      of the dosimetric indices (D90, V100, V400), the radiograph-based seed
      coordinates were transformed to the coordinate system of the CT postplan.
      Afterwards, the CT-based seed positions were replaced by the radiograph-based
      coordinates in the TPS and the dose distribution was recalculated. RESULTS: The
      computations demonstrated that the radiograph-based dosimetric values for the
      prostate (D(p)90, V(p)100, and V(p)400) were on average lower than the values of
      the CT postplan. Normalized to the CT postplan the following mean values were
      found: D(p)90: 90.6% (standard deviation [SD]: 9.0%), V(p)100: 86.1% (SD: 14.7%),
      and V(p)400: 79.4% (SD: 14.4%). For three out of the eight patients the D(p)90
      decreased to 90% of the initial CT postplan values. The reason for this
      dosimetric difference is supposed to be evoked by an error of the reconstruction
      software used. It was detected that the TPS algorithm assigned some sources to
      wrong coordinates, partly out of the prostate gland. CONCLUSION: The radiograph
      based postplanning technique of the investigated TPS should only be used in
      combination with CT postplanning. Furthermore, complex testing procedures of
      reconstruction algorithms are recommended to minimize calculation errors.

PMID- 16447017
TI  - High-dose-rate (HDR) or pulsed-dose-rate (PDR) perioperative interstitial
      intensity-modulated brachytherapy (IMBT) for local recurrences of previously
      irradiated breast or thoracic wall following breast cancer.
AB  - PURPOSE: In patients receiving salvage high-dose-rate (HDR) or pulsed-dose-rate
      (PDR) brachytherapy for a local recurrence on the chest wall or in the previously
      treated breast, clinical outcome and benefit were investigated. All patients had
      previously been treated with full-dose adjuvant external-beam irradiation (EBRT).
      Disease-free interval after salvage treatment, local tumor control and side
      effects were analyzed retrospectively. PATIENTS AND METHODS: Between 1996 and
      2002, a total of 32 consecutive patients were treated. 13 patients initially
      treated with mastectomy and postoperative irradiation and 19 patients initially
      treated with breast-conserving surgery and postoperative irradiation developed a
      local recurrence. The mean dose of previous radiation therapy was 58 Gy (range,
      42-64 Gy), applied by conventional fractionation. After implantation +/- surgery
      of recurrent disease and CT-based 3-D planning, 15 patients were irradiated with
      HDR-IMBT (intensity-modulated brachytherapy) with a mean dose of 28 Gy (range, 10
      30 Gy, 2 x 2.5 Gy/day at 6-h daily interfraction interval) and 17 patients
      received PDR-IMBT with a mean dose 30 Gy (range, 10-45 Gy, 5 x 1 Gy/day at 2-h
      pulse intervals). Four patients underwent additional EBRT using a dose of 24-40
      Gy electrons. Treatment was performed only on working days. RESULTS: After a mean
      post-implant follow-up of 19 months (range, 1-83 months), no signs of local
      recurrence were observed in 20 of the 32 patients. In twelve patients, local
      recurrence occurred after a mean follow-up of 13 months (range, 1-78 months). 20
      of the 32 patients experienced an additional systemic progress. In one patient,
      an EORTC/RTOG grade 3 side effect (ulceration of the skin) was described, which
      was followed by a local recurrence 12 months posttherapeutically. CONCLUSION:
      Perioperative interstitial HDR/PDR-IMBT of localized breast or thoracic wall
      recurrences following previous full-dose EBRT appears to be a meaningful salvage
      treatment with acceptable toxicity.

PMID- 16447018
TI  - Electromagnetically navigated brachytherapy as a new treatment option for
      peripheral pulmonary tumors.
AB  - PURPOSE: This technical note describes the principles of navigated brachytherapy
      for treatment of peripheral non-small cell lung cancer (NSCLC). MATERIAL AND
      METHODS: In a prospective feasibility trial a first patient with medically
      inoperable NSCLC in the right upper lobe was treated with external-beam
      radiotherapy (50 Gy) and navigated endoluminal brachytherapy (15 Gy). Navigated
      bronchoscopy was performed with an electromagnetic navigation system for
      localization of a microsensor mounted on the tip of a dedicated catheter placed
      within the working channel of a bronchoscope. The probe can be actively guided by
      a steering mechanism to targeted lesions in the periphery of the lung. After
      successful localization of the NSCLC, endobronchial ultrasound (EBUS) was
      performed to confirm the exact position in the center of the lesion. A 6-F
      brachytherapy catheter was placed within the tumor. Primary 3-D-planned
      brachytherapy was performed on chest CTs acquired with the inserted catheter.
      High-dose-rate brachytherapy (370 GBq iridium-192) was applied as a boost three
      times a week (single dose 5 Gy) and provided highly conformal irradiations of the
      NSCLC including the draining bronchovascular bundle. RESULTS: The brachytherapy
      catheter was tolerated well during treatment (5 days) and alimentation was
      possible without any problems. Repeated CTs showed stable positioning of the
      catheter. During follow-up (12 months), endoluminal ultrasound and CT
      demonstrated a partial remission while histology showed a complete remission of
      the tumor. CONCLUSION: Navigated brachytherapy for peripheral pulmonary tumors
      not amenable to conventional bronchoscopy is feasible.

PMID- 16447019
TI  - Paraneoplastic changes of oropharyngeal mucosa in breast cancer.
AB  - BACKGROUND: Paraneoplasias in the oral cavity are uncommon and have been rarely
      described so far. A woman with isolated papillomatosis and keratosis of
      oropharyngeal epithelia is reported. CASE REPORT: In a 43-year-old woman
      suffering from breast cancer, extensive changes of oropharyngeal epithelia were
      apparent 2.5 years after primary surgery and combined radiochemotherapy (RCT) as
      well as relapse therapy with RCT. At that time, radiologic investigations showed
      no locoregional or distant metastases. Nevertheless, after removal of the upper
      lip changes and skin resurfacing of the upper lip, progression of the
      oropharyngeal and labial changes was registered. Subsequent restaging showed
      advanced liver metastases. After treatment of the liver metastases, a regression
      of the extensive oropharyngeal changes became apparent. CONCLUSION: The
      appearance of untypical changes of oropharyngeal epithelia is suspective of
      paraneoplasia. In order to diagnose tumor recurrence, a restaging should be
      performed.

PMID- 16447020
TI  - Force systems in the initial phase of orthodontic treatment -- a comparison of
      different leveling arch wires.
AB  - BACKGROUND AND AIM: The determination of orthodontically-effective forces and
      moments places great demands on the technical equipment. Many patients report
      severe pain after fixed appliance insertion. Since it is assumed that pain from
      orthodontic appliances is associated with the force and moment levels applied to
      the teeth and since the occurrence of root resorption is a common therapeutic
      side effect, it would seem important to know the actual magnitudes of the
      components of the active orthodontic force systems. The aim of the present study
      was therefore to measure initial force systems produced by different leveling
      arch-wires in a complete multi-bracket appliance and to assess whether force and
      moment levels can be regarded as biologically acceptable or not. MATERIAL AND
      METHODS: The actual bracket position in 42 patients was transferred onto a
      measurement model. Forces and moments produced by a super-elastic nickel-titanium
      (NiTi) archwire, a 6-strand stainless steel archwire, and a 7-strand super
      elastic NiTi archwire were determined experimentally on different teeth. RESULTS:
      Average forces and moments produced by the super-elastic NiTi arch wires were
      found to be the highest. In spite if their larger diameter, the stranded arch
      wires' average force and moment levels were lower, especially that of the
      stranded super-elastic archwire. Nevertheless, maximum force levels sometimes
      exceeded recommended values in the literature and must be considered as too high.
      CONCLUSIONS: The measured arch wires' initial force systems differed
      significantly depending on the type of archwire and its material structure.
      Stranded arch wires produced lower force and moment levels, and we recommend
      their use in the initial phase of orthodontic treatment.

PMID- 16447021
TI  - Initial results regarding force exertion during rapid maxillary expansion in
      children.
AB  - AIM AND METHOD: We developed a method to measure the forces occurring during
      rapid maxillary expansion and carried out the University of Ulm rapid maxillary
      expansion method, similar to that of Chatellier and Chateau, in ten patients.
      RESULTS: The forces occurring on the maxilla increased up to 120 N. There was
      considerable variation in force level from patient to patient. After "rupture" of
      the midpalatal suture, the forces decreased. The remaining forces seemed to be
      the result from stress on soft tissue and bone.

PMID- 16447022
TI  - Molar and canine occlusal changes in study casts before and after treatment with
      cervical headgears.
AB  - AIM: We carried out a retrospective study on 246 pairs of casts to compare the
      extent of changes in occlusal relationship and overjet reduction induced by
      cervical headgears. MATERIAL AMD METHODS: Molar-canine occlusal relationships and
      overjet were determined from study casts made immediately before headgear
      treatment. Those findings were then compared to another cast made immediately
      after headgear monotherapy and before multiband-appliance administration.
      Headgear treatment lasted at least 6 months. Only patients whose upper first
      molars were distalized by at least 4 mm were included. RESULTS: Strikingly, the
      distalization and overjet reduction induced by headgear treatment were most
      pronounced in posterior positions and decreased progressively toward more
      anterior positions along the arch. The mean amount of distalization was 6.87 mm
      at molar, and 1.87 mm at canine positions. The mean reduction of initial overjet
      was 0.78 mm. No significant differences resulted by grouping the data based on
      upper anterior tooth inclinations before treatment. Significant differences,
      however, were obtained by grouping the data based on initial overjet.
      Significantly greater changes in molar-canine occlusal relationships and overjet
      reductions were observed in patients with a major initial overjet of > 6 mm than
      in those with a relatively minor overjet of < 4 mm.

PMID- 16447023
TI  - Wisdom tooth eruption secondary to localized lower molar mesialization in
      patients with aplastic lower second premolars.
AB  - OBJECTIVE: After localized space closure in the mandible it is desirable to
      preserve lower wisdom teeth as natural replacements for missing second premolars
      and as antagonists for upper second molars. The aim of this study was to
      determine whether this treatment method can obviate the need for prosthodontic
      restorations, implants, and third molar osteotomy. Furthermore the time point of
      possible third molar eruption was to be determined and whether further
      orthodontic interventions were required to achieve their alignment. PATIENTS AND
      METHODS: The test group comprised 34 patients who exhibited agenesis of one or
      both lower second premolars (n = 45) in conjunction with a corresponding number
      of third molar tooth germs. Follow-up examinations were performed 2 to 8 years
      after conclusion of orthodontic treatment involving push-and-pull mechanics (PPM)
      without extraction of any contralateral teeth. The results of the clinical
      retrospective follow-up examination at consecutive post-treatment endpoints were
      compared with two orthodontic control groups (A: 4-premolar extraction group, B:
      non-extraction group). RESULTS: After an average of 4 years and 2 months, the
      percentage of fully-erupted third molars in the agenesis group with localized
      space closure was 82%, compared to 29% and 28%, respectively, in the controls.
      These differences were statistically significant (p < or = 0.01). The success
      rate in the agenesis group reached 94% when the 4- to 8-year results were
      considered in isolation. Compared with the contralateral (non-aplastic) side,
      teeth on the aplastic side erupted prematurely. In 9% of the cases, minor
      orthodontic interventions were required to exactly position the third molars.
      CONCLUSION: There is high probability that mandibular third molars can be
      preserved after localized space closure, obviating the need for prosthodontic
      restorations, dental implants, and third molar osteotomies.

PMID- 16447024
TI  - Incisor trauma and the planning of orthodontic treatment.
AB  - Because of the frequency of dental injuries during infancy and adolescence,
      traumatized teeth with variable long-term prognoses present a problem for
      orthodontic treatment planning. Orthodontic therapy can remain unaffected, or be
      complicated, by traumatized teeth. In some cases, following dental injury,
      orthodontics can also be used to enhance (prosthetic and) restorative treatment
      results. The orthodontic challenges involved in treating patients with a history
      of dental trauma are complicated by the consequences of trauma on dentition
      development and the different treatment options that must be considered. In this
      paper, we provide actual examples of the effects dental trauma can have on
      orthodontic treatment planning.

PMID- 16447025
TI  - Orthodontic procedures in the treatment of obstructive sleep apnea in children.
AB  - INTRODUCTION: Even minor dimensional changes in the child's upper airway can
      already affect the resistance therein. Craniofacial anomalies may constrict the
      upper airway and are suspected to be a direct cause of obstructive sleep apnea
      syndrome (OSAS) in children. CASE REPORTS: In the present two cases we report on
      the successful orthodontic treatment of an 8-year-old girl and a 6 1/2-year-old
      boy with craniofacial anomalies and severe OSAS diagnosed during a sleep study.
      The primary treatment aim was to improve the cardio-respiratory situation during
      sleep by enlarging the upper airway and preventing its collapse. Prior to the
      onset of treatment we had ruled out the presence in both children of any
      adenotonsillar hypertrophy requiring surgical treatment. Patient 1 (the girl)
      presented mouth breathing predominantly while sleeping and a narrow skeletal
      maxilla that was treated via rapid maxillary expansion followed by a Frankel-II
      appliance. A function regulator type-II was applied in the second patient, a boy
      suffering from OSAS, and spinal muscular dystrophy with a narrow skeletal upper
      jaw and mandibular retrognathism. We were able to successfully treat both cases
      of obstructive sleep apnea with these orthodontic procedures. CONCLUSION:
      Orthodontic therapeutic measures should be considered as a causal treatment
      option in children with OSAS and craniofacial anomalies restricting the upper
      airway. Parents and patient cooperation, as well as good interdisciplinary care
      within the field of sleep medicine are mandatory for this kind of treatment.

PMID- 16447026
TI  - A comparison of North American versus non-North American ADHD study populations.
AB  - Few large, prospective clinical studies in Europe have assessed the validity and
      applicability of research methods used to study ADHD in North America. To assess
      comparability of study populations, we examined baseline patient characteristics
      from a group of North American studies against those of a large
      European/African/Australian study. All studies used identical diagnostic
      assessments and inclusion criteria, with ADHD diagnosis and the presence of
      comorbid psychiatric conditions confirmed using the KSADS-PL. Raters were trained
      and assessed to ensure uniform diagnostic and symptom severity rating standards.
      Six hundred and four patients (mean age = 10.2 years) enrolled in the non-North
      American study, and 665 patients (mean age = 10.4 years) enrolled in the North
      American study. The proportion of girls was higher in the North American studies
      (29.2% vs. 10.4%, p < 0.001). In both groups, most patients had a positive family
      history of ADHD and previous stimulant treatment. Fewer had the inattentive
      subtype of ADHD, and mean severity was slightly higher in the non-North American
      study. Results demonstrate that, when a uniform set of rigorous, standardized
      diagnostic criteria are used by skilled clinicians, the patient populations
      identified are generally similar. This supports the practice of generalizing
      results from treatment studies across geographies.

PMID- 16447027
TI  - Deliberate self-harm and childhood hyperactivity in junior high school students.
AB  - The present study aimed to explore the status of deliberate self-harm (DSH) among
      junior high-school students, and investigate the relationship between DSH and
      substance use and childhood hyperactivity. Subjects were 239 boys (mean age =
      14.16 years, SD = 0.67) and 238 girls (14.22, 0.68) from a junior high-school in
      Kanagawa, Japan. A self-reporting questionnaire consisting of original questions
      on self-cutting, self-hitting, and tobacco and alcohol use was employed with the
      Wender Utah Rating Scale (WURS) for assessing childhood hyperactivity. Overall,
      8.00% and 27.70% of males and 9.30% and 12.20% of females reported self-cutting
      and self-hitting, respectively. Regarding substance use, 33.10% and 74.10% of
      males and 14.30% and 63.40% of females reported tobacco and alcohol use,
      respectively. Comparisons of WURS scores between those with and without
      experience of problematic behaviors revealed that with all problematic behaviors
      in both genders, scores of those with experience were significantly higher than
      those without (P < 0.01 except for self-cutting in females, P < 0.05). The
      present study indicated that DSH is an important problem, even among children as
      young as junior high-school age. An association between DSH and childhood
      hyperactivity was also suggested.

PMID- 16447028
TI  - Social anxiety disorder in 11-12-year-old children: The efficacy of screening and
      issues in parent-child agreement.
AB  - OBJECTIVE: To investigate the level of diagnostic and discriminative accuracy of
      The Social Anxiety Scale for Children - Revised (SASC-R) for identifying social
      anxiety disorder (SAD) in a community-based sample of 11-12 year-old children.
      Parent-child diagnostic agreement was also examined. METHOD: A questionnaire
      including SASC-R and items on impulsive behavior was sent to a population based
      sample of children, born in 1992. A total of 2568 parents returned their
      questionnaires (rr: 70%), and 1297 (51%) consented to further participation. An
      index group [50 high-scoring children on social anxiety (SA-group)] and two
      contrast groups [(50 high-scoring children on impulsive behavior (Imp-group) and
      50 low-scoring children on SA and Imp, (Ls-group)] were selected for
      participation. RESULTS: SAD was assigned 35 (23%) of 150 children; 28 (80%) from
      the SA-group; 7 (20%) from the Imp- group and 0 from the Ls-group. The SASC-R
      showed relatively high discriminative accuracy for SAD, but was also influenced
      by other diagnoses. Mother-child agreement was fair (kappa = 0.46), and mother
      only diagnoses were frequent. Both child and parent information are important
      when diagnosing SAD in this age group.

PMID- 16447029
TI  - Chemical characterisation of organic electron donors for sulfate reduction for
      potential use in acid mine drainage treatment.
AB  - The production of acid mine drainage (AMD) containing high amounts of sulfate,
      heavy metals and low pH is of increasing concern. AMD is highly corrosive and
      results in economic and environmental problems. Organic electron donors for
      sulfate reduction were chemically characterised for potential use in AMD
      treatment. This was done in a process to develop a correlation between chemical
      composition and the capacity to drive sulfate reduction. Potential organic
      electron donors for sulfate reduction were chemically characterised in terms of
      dry matter content, ash content, total Kjeldahl nitrogen, lignin content,
      cellulose content, crude fat, crude fibre, in vitro digestibility, water-soluble
      carbohydrates, total non-structural carbohydrates and starch content. The
      chemical composition of the organic electron donors was then compared to results
      obtained from pilot plant studies where the organic electron donors for sulfate
      reduction were evaluated in terms of sulfate reduction. The chemical composition
      of the carbon source severely impacted its capacity to drive sulfate reduction
      and may be used to assist in predicting the sulfate reduction capacity of a
      carbon source. Organic electron donors for sulfate reduction high in protein
      content and low in lignin content or high in carbohydrate and crude fat content
      increased the capacity of a carbon source to drive sulfate reduction. The higher
      the fibre content of a carbon source, the lower the capacity to drive sulfate
      reduction. No correlation could be drawn between % dry matter, % ash content and
      sulfate reduction for the organic electron donors tested. Chemical
      characterisation can be used to assist in predicting sulfate reduction capacity
      of organic electron donors.

PMID- 16447030
TI  - Progress toward delisting a Great Lakes Area of Concern: the role of integrated
      research and monitoring in the Hamilton Harbour Remedial Action Plan.
AB  - The goal of restoring environmental health and qualities to Hamilton Harbour
      Great Lakes Area of Concern, an embayment at the western end of Lake Ontario, is
      considered to be achievable by the year 2015. Restoring Hamilton Harbour is a
      dynamic process that relies heavily on research and monitoring to direct
      remediation efforts. Three principle means of coordinating this research and
      monitoring include: research and monitoring workshops; a monitoring catalogue
      outlining both government and nongovernment initiatives; and an annual report
      written by a local community group. These tools increase the effectiveness of
      remedial actions by: (i) improving stakeholders' ability to track trends; (ii)
      allowing program decision-makers to utilize adaptive management techniques to
      continuously modify programs based on new results; (iii) integrating
      interdisciplinary fields, and (iv) increasing accountability. This paper
      describes in detail these tools used for coordinating research and monitoring in
      implementing the Remedial Action Plan of the Hamilton Harbour Great Lakes Area of
      Concern, along with lessons learned to assist other implementers who are
      considering similar programs.

PMID- 16447031
TI  - Photosynthesis research in Canada from 1945 to the early 1970s.
AB  - This history traces the development of photosynthesis research in Canada from
      1945 to 1975, starting with the work of Gleb(1) Krotkov and his students, Paul
      Vittorio, Tony(1) Bidwell, Don(1) Nelson, Jim(1) Craigie, Bruce Tregunna, Andreas
      Hauschild, Geoff Lister and others in the Department of Biology at Queen's
      University, Kingston, Ontario. They focused on the influence of taxonomy and
      light quality on the path of carbon into early products, photorespiration and
      photosynthesis in young trees. During the same period, Ken(1) Clendenning and one
      of the authors (PRG) at the National Research Council of Canada (NRCC) laboratory
      in Ottawa began studies of chloroplast photoreduction and leaf carboxylases. They
      were joined by Don(1) Mortimer, who showed that the path of carbon varies with
      species of plant and by Morris Kates, who studied phospholipid enzymology in
      chloroplasts and leaves. Stan(1) Holt researched the chemistry and distribution
      of chlorophylls in different taxa. In 1952, Ralph Lewin joined NRCC's new
      Atlantic Regional Laboratory in Halifax, Nova Scotia, followed by Jim Craigie,
      Jack McLachlan and Tony Bidwell who mainly investigated the products of
      photosynthesis in marine algae. Tony Bidwell continued these studies in 1959 at
      the Department of Botany, University of Toronto. Dave(1) Canvin joined the staff
      at Queen's in 1965 and became involved in solving the mystery of
      photorespiration. Tony Bidwell returned to Queen's in 1969 and studied
      photosynthesis of algal chloroplasts using an 'artificial leaf.' In 1965, Don
      Nelson established a group at Simon Fraser University in Burnaby, British
      Columbia that included his former student, Geoff Lister who produced the first
      photosynthetic action spectra for trees, and Bill(1) Vidaver, who showed the
      useful relation between chlorophyll fluorescence and photosynthetic activity. In
      1970, Mario Fragata headed a group at the Universite du Quebec a Trois Rivieres,
      Quebec, that began with studies of Photosystem II in chloroplasts and particles.

PMID- 16447032
TI  - Treatment of anastomotic leakage after rectal resection with transrectal vacuum
      assisted drainage (VAC). A method for rapid control of pelvic sepsis and healing.
AB  - OBJECTIVE: Anastomotic leakage after rectal resection is associated with high
      morbidity and mortality. Patients without peritonitis can be treated
      conservatively by transrectal rinsing and drainage. However, healing is often
      very slow, and formation of abundant scar tissue resulting in a poor functional
      result is not uncommon. Vacuum-assisted closure (VAC) has been shown to
      accelerate wound healing by increasing local blood flow, reducing bacterial load
      and stimulating growth of granulation tissue. In this paper, we describe VAC as a
      method for treating anastomotic leakage after rectal resection. METHODS: Four
      patients with anastomotic leakage after rectal resections were treated with VAC.
      RESULTS: Healing time for these patients was median 51 days (43-195). The control
      group consisted of patients treated conservatively in the previous 5-year period.
      Ten patients were identified with median healing time 336 days (52-1434).
      CONCLUSION: VAC treatment may possibly shorten healing time of anastomotic
      leakages after rectal resection. However, the presented results are preliminary,
      with only few patients included, and obviously, larger, randomized, clinical
      trials are needed to confirm these results and establish the indication for VAC
      treatment in clinical practice. We believe VAC therapy is a promising treatment
      of anastomotic leakage after rectal resection.

PMID- 16447033
TI  - The influence of hyperchloraemia on acid base interpretation in diabetic
      ketoacidosis.
AB  - OBJECTIVES: During the acute treatment of diabetic ketoacidosis we (a) determined
      the temporal incidence of hyperchloraemia, and (b) quantified the influence of
      hyperchloraemia on interpretation of common blood gas derived acid base
      parameters, namely base deficit and bicarbonate. DESIGN AND SETTING:
      Retrospective chart review in two regional paediatric intensive care units.
      MEASUREMENTS AND RESULTS: Stewart's physicochemical theory was used to develop
      regression equations quantifying the acidifying effect of hyperchloraemia on both
      base deficit and bicarbonate. These were then applied retrospectively to blood
      chemistry results from 18 children (median age 12.7 years, weight 43 kg) with
      diabetic ketoacidosis. Plasma ketonaemia was estimated using the albumin
      corrected anion gap. The incidence of hyperchloraemia, as documented by a ratio
      of plasma chloride to sodium of greater than 0.79, increased from 6% at admission
      to 94% after 20 h of treatment. Correction for chloride produced a dramatic
      improvement in the relationship between changes in the anion gap vs. both base
      deficit (from R(2)=0.55 to R(2)=0.95) and bicarbonate (from R(2)=0.51 to
      R(2)=0.96) during treatment. After 20 h of treatment the mean base deficit had
      decreased from 24.7 mmol/l to 10.0 mmol/l however, the proportion that was due to
      hyperchloraemia increased from 2% to 98%. CONCLUSIONS: It is now possible using a
      simple correction factor to quantify the confounding effect of hyperchloraemia on
      both base deficit and bicarbonate in diabetic ketoacidosis. This bedside tool may
      be a useful adjunct to guide therapeutic interventions.

PMID- 16447034
TI  - [Influence of gender on stimulated cytokine response in patients with severe
      sepsis].
AB  - AIM: Studies suggest that female mice have lower mortality rates than males after
      sepsis or trauma-hemorrhage. This study investigated the impact of gender and
      disease severity on monocyte hyporesponsiveness in severe human sepsis. METHODS:
      We prospectively investigated 49 (male n=28, female n=21) consecutive patients
      with severe sepsis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10
      (IL-10) were assayed by ELISA in unstimulated whole blood cultures or after
      stimulation with lipopolysaccharide (LPS; E. coli 0111:B4) or Staph. aureus Cowan
      strain I (SAC-I) lysate at days 1, 2, 3, 4, and 8 after enrollment. Testosterone
      and estradiol levels were quantified by electrochemoluminescence immunoassays.
      RESULTS: Mortality was similar for males (35.7%) and females (42.9%). While
      disease severity was also comparable, septic patients showed a substantial
      suppression in stimulated TNF-alpha response compared to healthy controls who
      recovered within 8 days in surviving patients. Stimulated cytokine response
      recovered in female non-surviving patients, while it remained suppressed in non
      surviving male patients and was significantly different compared to female non
      surviving patients. Testosterone levels were substantially suppressed in male but
      not female septic patients compared to normal values but did not differ between
      surviving and non-surviving patients. Estradiol levels were elevated in female
      and male septic patients. Addition of different concentrations of testosterone
      and estradiol to whole blood obtained from younger (<35 years old) and older (>60
      years old) male as well as from younger (proestrous premenopausal) and older
      (postmenopausal) female non-septic volunteers revealed no effect on LPS
      stimulated TNF-alpha and IL-10 release. CONCLUSION: Severe sepsis leads to a
      substantial suppression of stimulated cytokine response. Prolonged suppression
      may serve as a marker of unfavourable outcome in male but not in female
      individuals suffering from severe sepsis. Furthermore, our data suggest that
      gender differences in cellular immunity described for young, sexually mature
      animals obviously persist in typical postmenopausal intensive care unit patients,
      although a direct interaction between testosterone or estradiol and LPS
      stimulated cytokine response could not be demonstrated.

PMID- 16447037
TI  - Pattern of T2 hypointensity associated with ring-enhancing brain lesions can help
      to differentiate pathology.
AB  - Ring-enhancing lesions seen on MR images can occur with a variety of etiologies.
      Some ring-enhancing lesions have hypointense rims peripherally on T2-weighted MR
      images. In this study, we examined whether T2 hypointense rims were associated
      with specific pathologies. A search for ring-enhancing lesions on MR images
      obtained from 1996 to 2004 was performed, and revealed 221 patients with MRI
      findings of ring enhancement. The pattern of T2 hypointensity (arc or rim)
      corresponding with ring enhancement was recorded. In addition, we analyzed other
      imaging characteristics, including signal on diffusion-weighted images, central
      homogeneity on T2 and multiplicity of lesions. We then reviewed clinical data on
      the patients to ascertain the diagnosis for each examination. The most common
      associated pathologies in our study were gliomas (40%), metastases (30%),
      abscesses (8%) and multiple sclerosis (MS; 6%). Hypointense borders on T2
      weighted images were present in 67% of lesions in the form of a rim in 40% and an
      arc in 60%. Abscesses had the highest percentage of hypointense rims. Metastases
      and gliomas more commonly had arcs, and MS lesions were divided between rims and
      arcs. Abscesses and MS lesions were more commonly homogeneous centrally, compared
      to gliomas and metastases. Additionally, abscesses were more often bright on
      diffusion imaging than the other pathologies. As expected, abscesses and MS
      lesions were usually multiple, whereas metastases were typically multiple in
      approximately 50% of the patients; gliomas were generally solitary. Trends in T2
      hypointensity may aid in distinguishing among etiologies of ring-enhancing
      lesions, although there is overlap between the MR appearance of these various
      pathologies.

PMID- 16447036
TI  - A meta-analysis of exercise interventions among people treated for cancer.
AB  - GOAL: This review applied meta-analytic procedures to integrate primary research
      findings that tested exercise interventions among people treated for cancer.
      METHODS: Extensive literature searching strategies located published and
      unpublished intervention studies that tested exercise interventions with at least
      five participants (k = 30). Primary study results were coded. Meta-analytic
      procedures were conducted. MAIN RESULTS: The overall weighted mean effect size
      (ES) for two-group comparisons was 0.52 (higher mean for treatment than control)
      for physical function, 0.35 for symptoms other than fatigue, and 0.27 for body
      composition. More modest positive ESs were documented for mood (0.19), quality of
      life (0.14), fatigue (0.11), and exercise behavior (0.04). ESs were larger among
      single-group pre-post design studies. ESs among control group participants were
      typically negative and not (statistically) significantly different from 0.
      CONCLUSIONS: Exercise interventions resulted in small positive effects on health
      and well-being outcomes among existing studies. Future research should examine
      intervention-specific characteristics that result in optimal results, such as
      dose.

PMID- 16447035
TI  - [Long QT syndrome and anaesthesia].
AB  - The long QT syndrome (LQTS) is a rare, congenital or acquired disease, which may
      lead to fatal cardiac arrhythmias (torsade de pointes, TdP). In all LQTS
      subtypes, TdPs are caused by disturbances in cardiac ion channels. Diagnosis is
      made using clinical, anamnestic and electrocardiographic data. Triggers of TdPs
      are numerous and should be avoided perioperatively. Sufficient sedation and
      preoperative correction of electrolyte imbalances are essential. Volatile
      anaesthetics and antagonists of muscle relaxants should be avoided and high doses
      of local anaesthetics are not recommended to date. Propofol is safe for
      anaesthesia induction and maintenance. The acute therapy of TdPs with
      cardiovascular depression should be performed in accordance with the guidelines
      for advanced cardiac life support and includes cardioversion/defibrillation and
      magnesium. Torsades de pointes may be associated with bradycardia or tachycardia
      resulting in specific therapeutic and prophylactic measures.

PMID- 16447038
TI  - Thin liquid films and monolayers of DMPC mixed with PEG and phospholipid linked
      PEG.
AB  - In this work thin liquid films (TLFs) and monolayers at the air/water interface
      formed by dimyristoylphosphatidylcholine (DMPC) and by DMPC mixed with poly
      ethylene glycols (PEGs) and dimyristoylphosphatidylethanolamine (DMPE) linked
      PEGs were studied. Film forming dispersions were composed of two types of
      particles: liposomes and micelles. TLFs stability, threshold concentration C(t)
      (i.e., the minimum one for stable film formation), and hydrodynamic behavior were
      measured. At equivalent conditions, DMPC films were Newton black films (real
      bilayers), while DMPE-PEGs films were much thicker with free water between the
      monolayers. DMPE-PEG addition to DMPC films caused both C(t) decrease (depending
      on PEG moiety length and Mw) and change of TLF formation mechanism. TLFs'
      hydrodynamic behavior also strongly depended on DMPE-PEG content and Mw. It was
      observed that thinning of the DMPC and DMPE-PEGs films continued to different
      film types and thickness, being much thicker for the latter films. Addition of
      free PEGs (PEG-200/6000) did not alter TLF type or stability, but changed TLF
      thinning time, confirming that free PEGs with Mw<8000 could not penetrate in the
      membrane and alter "near-membrane" water layer viscosity. Monolayer studies
      showed improved formation kinetics of both adsorbed and spread films, decrease of
      surface tension (equilibrium and dynamic), and of film compression/decompression
      histeresis area in DMPE-PEGs monolayers compared with DMPC pure films. Our study
      shows that combining the models of phospholipid TLFs and monolayers provide the
      opportunity to investigate the properties of membrane surface and to clarify some
      mechanisms of its interactions with membrane-active agents.

PMID- 16447039
TI  - Targeting cancer cells: magnetic nanoparticles as drug carriers.
AB  - Magnetic drug targeting employing nanoparticles as carriers is a promising cancer
      treatment avoiding side effects of conventional chemotherapy. We used iron oxide
      nanoparticles covered by starch derivatives with phosphate groups which bound
      mitoxantrone as chemotherapeutikum. In this letter we show that a strong magnetic
      field gradient at the tumour location accumulates the nanoparticles. Electron
      microscope investigations show that the ferrofluids can be enriched in tumour
      tissue and tumour cells.

PMID- 16447041
TI  - Pilot phase II study of weekly chemotherapy with paclitaxel and carboplatin for
      refractory or relapsed small-cell lung cancer.
AB  - PURPOSE: The safety and efficacy of weekly chemotherapy with paclitaxel and
      carboplatin for the treatment of patients with refractory or relapsed small-cell
      lung cancer (SCLC) were evaluated. PATIENTS AND METHODS: Paclitaxel (100 mg/m(2))
      and carboplatin (with a target area under the concentration versus time curve of
      2 mg min/ml using the Calvert formula) were administered to patients with
      previously- treated SCLC on days 1 and 8 at every 3-4 weeks. RESULTS: A total of
      29 patients (pts) [male/female, 26/3 pts; median age 62.7 years (43-74);
      performance status 0/1/2, 9/10/10 pts] were enrolled between March 2000 and June
      2002. The mean number of cycles administered per pt was 3 (1-7). The overall
      response rate was 69% (95% confidence interval 52-86%), and 83% (15/18) in
      sensitive pts and 45% (5/11) in refractory pts (P<0.01). The overall median
      survival time was 29.6 weeks with a 1-year survival rate of 37% [34.1 weeks in
      sensitive pts and 23.1 weeks in refractory pts (P=0.085), 46.9 weeks in PS 0-1
      and 16.3 weeks in PS 2 (P<0.001)]. The median time to progressive disease was
      16.4 weeks [21.7 weeks in sensitive pts and 15.3 weeks in refractory pts
      (P=0.32)]. Hematologic toxicities observed included grade >or=3 neutropenia in
      55%, grade >or=3 anemia in 36%, and grade >or=3 thrombocytopenia in 3%. Non
      hematologic toxicities were mild except for grade 3 diarrhea in three pts and
      grade 3 pneumonitis in one pt. CONCLUSION: Weekly chemotherapy with paclitaxel
      and carboplatin was well- tolerated and gave a high-response rate in pts with
      refractory or relapsed small-cell lung cancer.

PMID- 16447042
TI  - Vascular malformations in the extremities: emphasis on MR imaging features that
      guide treatment options.
AB  - Vascular malformations can be classified into high-flow arteriovenous
      malformations (AVM) and low-flow venous or lymphatic malformations (VM/LM). VMs
      and LMs have the ability to cross multiple tissue boundaries. Not only is
      subcutaneous tissue often involved, but multiple muscle groups, tendons, bone
      cortex and bone marrow are also not uncommonly violated. Magnetic resonance
      imaging (MRI) provides valuable information for the assessment and treatment of
      malformations. Firstly, MRI can characterize the flow pattern of these
      malformations to guide treatment towards trans-arterial embolization for AVMs and
      percutaneous embolization for low flow malformations. MRI is essential to define
      the anatomic extent and involvement of various tissue layers (a distinct
      advantage over ultrasound), and to correlate treatable components of the
      malformation with patient symptoms. Treatment is decided by the need to alleviate
      clinical symptoms, and is dependent on the extent of the malformation as defined
      by MRI. We present MRI features of vascular malformations to demonstrate the
      potential spectrum of involvement of these lesions, illustrating the value of MRI
      in treatment planning.

PMID- 16447040
TI  - Gastric and intestinal phenotypic cell marker expressions in gastric
      differentiated-type carcinomas: association with E-cadherin expression and
      chromosomal changes.
AB  - Gastric and intestinal phenotypic cell markers are widely expressed in gastric
      carcinomas, irrespective of their histological type. In the present study, the
      relations between the phenotypic marker expression of the tumour, histological
      findings, expression of cell adhesion molecules, and the chromosomal changes in
      gastric differentiated-type carcinomas were examined. The phenotypic marker
      expression of the tumour was determined by the combination of the expression of
      the human gastric mucin (HGM), MUC6, MUC2 and CD10, and was evaluated in
      comparison with the expression of cell adhesion molecules, such as E-cadherin and
      beta-catenin, and chromosomal changes by comparative genomic hybridization (CGH)
      in 34 gastric differentiated-type carcinomas. Tumours were classified into the
      gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or
      unclassified- (UC-) phenotype according to the immunopositivity of staining for
      HGM, MUC6, MUC2, and CD10. G-phenotype tumours were significantly associated with
      a higher incidence of differentiated-type tumours mixed with undifferentiated
      type component, compared with GI- and I-phenotype tumours (88.9 vs 33.3%,
      P=0.0498 and 88.9 vs 42.9%, P=0.0397; respectively). HGM-positive tumours were
      significantly associated with a higher incidence of tumours with abnormal
      expression of E-cadherin, compared with HGM-negative tumours (66.7 vs 21.1%,
      P=0.0135). GI-phenotype tumours were significantly associated with a higher
      incidence of tumours with abnormal expression of E-cadherin, compared with I
      phenotype tumours (77.8 vs 21.4%, P=0.0131). HGM-negative tumours were
      significantly associated with higher frequencies of the gains of 19q13.2 and
      19q13.3, compared with HGM-positive tumours (57.9 vs 20.0%, P=0.0382 and 63.2 vs
      13.3%, P=0.0051; respectively). MUC6-positive tumours were significantly
      associated with higher frequencies of the gains of 20q13.2, compared with MUC6
      negative tumours (71.4 vs 30.0%, P=0.0349). MUC2-positive tumours were
      significantly associated with the gain of 19p13.3, compared with MUC2-negative
      tumours (41.2 vs 5.9%, P=0.0391). I-phenotype tumours were significantly
      associated with higher frequencies of gains of 5p15.2 and 13q33-34, compared with
      G-phenotype tumours (66.7 vs 0%, P=0.0481, each) and also associated with higher
      frequencies of gain of 7p21, compared with GI-phenotype tumours (66.7 vs 0%,
      P=0.0481). Our present results show that gastric differentiated-type carcinomas
      have different characteristics according to the phenotypic marker expression of
      the tumour in terms of histological findings, E-cadherin expression and pattern
      of chromosomal changes.

PMID- 16447043
TI  - Selection of reference films based on reliability assessment of a classification
      of high-resolution computed tomography for pneumoconioses.
AB  - OBJECTIVE: Worldwide demand has increased for the development of a computed
      tomography (CT) classification system that supplements the ILO classification of
      radiographs for pneumoconioses. The authors aimed to show preliminary reliability
      test results for selected referent films for the CT classification system
      developed through an international effort by researchers from seven countries.
      METHODS: Reading trials by eight physicians who have considerable experience in
      pneumoconioses using a total of 114 lung zones consisting of 6 lung zones of 19
      CT films of dust-exposed workers were performed to assess reliability of the
      classification system by weighted kappa. The results were also utilized for
      selecting reference films. RESULTS: A good agreement was observed for both first
      and second reading trials for rounded opacities (weighted kappa=0.76, 0.74, first
      and second trial results, respectively), irregular opacities (0.60, 0.48),
      emphysema (0.56, 0.70) and honeycombing (0.72, 0.79). Ground glass opacities, on
      the other hand, showed moderate agreement (0.43, 0.38). Intra-reader agreements
      among eight readers were shown in the same table as the mean and standard
      deviation of weighted kappa statistics. The inter-reader agreement for pleural
      thickening was not as good as for parenchymal lesions. DISCUSSION: The CT
      classification development may pioneer noble and sensitive medical screening for
      dust-exposed workers in selected settings. This system may be applied to
      radiographic borderline cases of profusion 0/1 and 1/0 by the ILO classification,
      in a setting that assures the occupational safety and health of workers exposed
      to some newly developed chemical compounds.

PMID- 16447044
TI  - Detection of oncoprotein platelet-derived growth factor using a fluorescent
      signaling complex of an aptamer and TOTO.
AB  - There have recently been advances in the application of aptamers, a new class of
      nucleic acids that bind specifically with target proteins, as protein recognition
      probes for biomedical study. The development of a signaling aptamer with the
      capability of simple and rapid real-time detection of disease-related proteins
      has attracted increasing interest. We have recently reported a new protein
      detection strategy using a signaling aptamer based on a DNA molecular light
      switching complex, [Ru(phen)2(dppz)]2+. In this work we have used the
      commercially available DNA-intercalating dye, TOTO, to replace
      [Ru(phen)2(dppz)]2+ for detection of oncoprotein platelet-derived growth factor
      BB (PDGF-BB), a potential cancer marker. Taking advantage of the high affinity of
      the aptamer to PDGF-BB and the sensitive fluorescence change of the aptamer-TOTO
      signaling complex on protein binding, PDGF-BB was detected in physiological
      buffer with high selectivity and sensitivity. The detection limit was 0.1 nmol L(
      1), which was better than that of other reported aptamer-based methods for PDGF
      BB, including that using [Ru(phen)2(dppz)]2+. The method is very simple with no
      need for covalent labeling of the aptamer or probe synthesis. It facilitates wide
      application of the signaling mechanism to the analysis and study of cancer
      markers and other proteins.

PMID- 16447045
TI  - Long-term assessment of striatal dopamine transporters in Parkinsonian patients
      with intrastriatal embryonic mesencephalic grafts.
AB  - PURPOSE: Single-photon emission computed tomography (SPECT) of striatal dopamine
      transporters (DAT) has been used to demonstrate presynaptic dopaminergic
      dysfunction and to monitor the progression of Parkinson's disease. In
      parkinsonian patients who were implanted with embryonic mesencephalic tissue in
      the striatum, positron emission tomography (PET) has shown an increase in
      striatal [(18)F]dopa uptake as an indicator of graft survival and striatal
      reinnervation. The aim of this study was to investigate two patients who had
      undergone bilateral intrastriatal transplantation of human embryonic
      mesencephalic tissue using SPECT and the (123)I-labelled DAT ligand N-(3
      iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (IPT).
      METHODS: Two patients were subjected to [(123)I]IPT SPECT according to a
      standardised protocol prospectively and repeatedly up to 8 years after
      transplantation. RESULTS: From baseline to year 3 after transplantation, mean
      striatal DAT availability increased by a mean of 61% (93% and 29% in patients 1
      and 2, respectively). It then remained relatively stable up to 8 years in patient
      2, but increased further by another 77% of baseline values in patient 1.
      Clinically, both patients experienced a moderate improvement in motor performance
      but developed moderate (patient 2) to severe (patient 1) off-medication
      dyskinesias. CONCLUSION: Our data indicate that DAT imaging using IPT and SPECT
      can be used to demonstrate graft survival following dopaminergic tissue
      implantation. Because SPECT with DAT ligands is widely available in the routine
      clinical setting, this methodology may be a useful alternative to [(18)F]dopa PET
      for repeated scanning of grafted parkinsonian patients. The relevance of the long
      term increase in DAT binding for the development of off-medication dyskinesias
      remains to be elucidated further.

PMID- 16447046
TI  - Identification and regulatory analysis of rainbow trout tapasin and tapasin
      related genes.
AB  - Tapasin (TAPBP) is a key member of MHC class Ia antigen-loading complexes,
      bridging the class Ia molecule to the transporter associated with antigen
      presentation (TAP). As part of an ongoing study of MHC genomics in rainbow trout,
      we have identified two rainbow trout TAPBP genes (Onmy-TAPBP.a and .b) and a
      similar but distinct TAPBP-related gene (Onmy-TAPBP-R) that had previously only
      been described in mammals. Physical and genetic mapping indicate that Onmy
      TAPBP.a is on chromosome 18 in the MHC class Ia region and that Onmy-TAPBP.b
      resides on chromosome 14 in the MHC class Ib region. There are also at least two
      copies of TAPBP-R, Onmy-TAPBP-R.a and Onmy-TAPBP-R.b, located on chromosomes 2
      and 3, respectively. Due to the central role of TAPBP expression during acute
      viral infection, we have characterized the transcriptional profile and regulatory
      regions for both Onmy-TAPBP and Onmy-TAPBP-R. Transcription of both genes
      increased during acute infection with infectious hematapoeitic necrosis virus
      (IHNV) in a fashion indicative of interferon-mediated regulation. Promoter
      reporter assays in STE-137 cells demonstrate that the trout TAPBP and TAPBP-R
      promoters respond to interferon regulatory factors, Onmy-IRF1 and Onmy-IRF2.
      Overall, TAPBP is expressed at higher levels than TAPBP-R in naive tissues and
      TAPBP transcription is more responsive to viral infection and IRF1 and 2 binding.

PMID- 16447048
TI  - Prostate biopsy in the supine position in a standard 1.5-T scanner under real
      time MR-imaging control using a MR-compatible endorectal biopsy device.
AB  - Thirty-seven consecutive patients with elevated PSA levels and negative tumor
      prostate biopsies underwent a MR-guided prostate biopsy in a 1.5-T scanner in the
      supine position. After localization of suspected tumor areas using an endorectal
      coil and two body-phased array coils, the biopsy device was positioned without
      any repositioning of the patient. The biopsy device consisted of a mount, a ball
      joint, a positioning stage and an insertion stage with a needle guide, which was
      filled with a MR-visible fluid to control positioning of the needle using a
      balanced steady-state free precession sequence (TrueFISP) and a high-resolution
      turbo spin echo (T2-TSE) sequence. Core biopsies were taken manually in the
      magnet. The biopsy needle could be correctly positioned in all cases. Suspected
      lesions with a diameter > or =10 mm could be successfully punctured. Four to nine
      (mean = 6) biopsies were taken per patient. In 14 patients, prostate cancer was
      confirmed at histology. Twenty-four biopsies positive for cancer were performed
      in 14 patients. A correct correlation was found between the site of biopsy and
      histology. MR-guided prostate biopsy can be effective in increasing primary
      positive tumor biopsy results in patients with a history of negative tumor TRUS
      guided prostate biopsies.

PMID- 16447047
TI  - Eighty-peak kilovoltage 16-channel multidetector computed tomography and reduced
      contrast-medium doses tailored to body weight to diagnose pulmonary embolism in
      azotaemic patients.
AB  - The aim of this study was to assess the feasibility of minimising contrast-medium
      (CM) doses using 80-peak kilovoltage (kVp) 16-channel multidetector computed
      tomography (MDCT) with CM dose tailored to body weight, when diagnosing pulmonary
      embolism (PE) in azotaemic patients. Twenty-nine patients (68-93 years; 38-79 kg)
      with an estimated glomerular filtration rate of 12-49 ml/min underwent 80 kVp
      MDCT at a median dose of 200 mg iodine (I)/kg and 15 s injection time. Pulmonary
      artery (PA) enhancement where compared with our own reference material using 320
      mg I/kg at 120 kVp and with reported figures in the literature at 120-140 kVp and
      a 42 g iodine CM dose. Median (1st and 3rd quartiles) values regarding CM dose
      were 12.2 (9.9-12.8) g iodine; density of left main and lower lobe segmental PA
      339 (275-395) Hounsfield units (HU) and 354 (321-442) HU, respectively. Those
      enhancement values were similar to those obtained from the reference population
      at 120 kVp and those reported in the literature at 120-140 kVp. One patient had a
      transient increase in plasma creatinine. Three months' follow-up revealed deep
      venous thrombosis among 1/18 patients with negative results from computed
      tomography (CT). We conclude that 80 kVp 16-channel MDCT to diagnose PE in
      azotaemic patients may be performed with markedly reduced CM doses, implying a
      lesser risk for CM-induced nephropathy.

PMID- 16447049
TI  - Using synthetic chemistry to understand copper protein active sites: a personal
      perspective.
AB  - The results of studies performed in the author's laboratory are surveyed, with
      particular emphasis on demonstrating the value of a multidisciplinary synthetic
      modeling approach for discovering new and unusual chemistry helpful for
      understanding the properties of the active sites of copper proteins or assessing
      the feasibility of mechanistic pathways they might follow during catalysis. The
      discussion focuses on the progress made to date toward comprehending the nitrite
      reductase catalytic site and mechanism, the electronic structures of copper
      thiolate electron transfer centers, the sulfido-bridged "CuZ" site in nitrous
      oxide reductase, and the processes of dioxygen binding and activation by mono-
      and dicopper centers in oxidases and oxygenases.

PMID- 16447050
TI  - Effect of fenofibrate on the level of asymmetric dimethylarginine in individuals
      with hypertriglyceridemia.
AB  - OBJECTIVE: To test whether treatment with fenofibrate decreases asymmetric
      dimethylarginine (ADMA) level in hypertriglyceridemic individuals. METHODS: In
      the present study, 45 subjects with hypertriglyceridemia were recruited to
      receive treatment with fenofibrate (200 mg/d). Serum concentrations of ADMA,
      malondialdehyde (MDA), nitric oxide (NO) and tumor necrosis factor-alpha (TNF
      alpha) were measured. Endothelial function assessed by flow-mediated dilation
      (FMD) of the brachial artery was performed. RESULTS: Compared with control, serum
      levels of ADMA (0.47+/-0.05 micromol/L in control and 0.62+/-0.28 micromol/L in
      hypertriglyceridemic patients, P<0.01), MDA and TNF-alpha were markedly elevated,
      and the level of NO was significantly reduced, concomitantly with impaired
      endothelium-dependent vasodilation in individuals with hypertriglyceridemia. 8
      week treatment with fenofibrate significantly reduced the elevated levels of ADMA
      (0.53+/-0.12 micromol/L, P<0.01), MDA and TNF-alpha, attenuated the decreased
      level of NO and improved endothelial function. CONCLUSIONS: These results suggest
      that the beneficial effect of fenofibrate on the endothelium in
      hypertriglyceridemic individuals may be related to reduction of ADMA level.

PMID- 16447052
TI  - Comparative analysis of HIV-1 recombinant envelope glycoproteins from different
      culture systems.
AB  - The productivity of stable Chinese hamster ovary cell lines secreting HIV-1
      monomeric (IIIB gp120) and oligomeric (UG21 gp140) recombinant envelope
      glycoproteins was compared in serum-containing (S+), serum-free (S-) and protein
      free (P-) culture media. UG21 gp140 expression was greatest in S+ medium, while
      IIIBgp120 production was lower than gp140 in all three media but highest in S-.
      UG21 gp140 production was highest in standard 850-cm2 roller bottle cultures in
      S+ media, peaking after 14 days of incubation, while expression levels in the
      three media were 0.5 (S+), 0.4 (S-) and 0.2 (P-) mg/l, from which 90, 80 and 12%
      of gp140, respectively, could be purified by immunoaffinity chromatography.
      Purified UG21 gp140 from S+ and S- media possessed biological functionality as
      evidenced by CD4 and monoclonal antibody (Mab) binding. In contrast, UG21 gp140
      from P- medium appears to be misfolded and non-functional. Despite the possession
      of a different N-linked glycan profile, UG21 gp140 from S- media shows very
      similar CD4 and Mab binding characteristics to S+ UG21 gp140. The relevance of
      these findings to HIV vaccine development is discussed.

PMID- 16447051
TI  - Pioglitazone, an in vitro inhibitor of CYP2C8 and CYP3A4, does not increase the
      plasma concentrations of the CYP2C8 and CYP3A4 substrate repaglinide.
AB  - OBJECTIVE: Pioglitazone, a thiazolidinedione antidiabetic, inhibits cytochrome
      P450 (CYP) 2C8 and CYP3A4 enzymes in vitro. Repaglinide, a meglitinide analogue
      antidiabetic, is metabolised by CYP2C8 and CYP3A4. In patients with type 2
      diabetes, the pioglitazone-repaglinide combination has acted synergistically on
      glycaemic parameters. Our aim was to determine whether pioglitazone increases the
      plasma concentrations of repaglinide. METHODS: In a randomized, 2-phase cross
      over study, 12 healthy volunteers received 30 mg pioglitazone or placebo once
      daily for 5 days. On day 5, they ingested a single 0.25 mg dose of repaglinide 1
      h after the last pretreatment dose. Plasma repaglinide and pioglitazone, and
      blood glucose concentrations were measured for 12 h. RESULTS: During the
      pioglitazone phase, the mean peak plasma repaglinide concentration (C(max)) and
      the total area under the concentration-time curve [AUC(0-infinity)] of
      repaglinide were 100% (range 53-157%, P=0.99) and 90% (range 63-120%, P=0.22),
      respectively, of those during the placebo phase. Also the half-life of
      repaglinide was unaffected, but the median peak time of repaglinide was shortened
      from 40 min to 20 min by pioglitazone (P=0.014). The short-term pioglitazone
      administration did not modify the blood glucose-lowering effect of a single dose
      of repaglinide. CONCLUSIONS: Pioglitazone does not increase the plasma
      concentrations of repaglinide, indicating that the inhibitory effect of
      pioglitazone on CYP2C8 and CYP3A4 is very weak in vivo, probably due to its
      extensive plasma protein binding. The synergistic effect of repaglinide and
      pioglitazone on the glycaemic parameters, seen in patients with type 2 diabetes
      during their long-term use, is unlikely to be caused by inhibition of repaglinide
      metabolism by pioglitazone.

PMID- 16447053
TI  - Differences in protein and energy metabolism following portal versus systemic
      administration of insulin in diabetic dogs.
AB  - AIMS/HYPOTHESIS: In non-diabetic people, insulin levels in the liver are two-fold
      higher than those in the systemic circulation. In contrast, patients with type 1
      diabetes have similar hepatic and systemic insulin levels because insulin is
      administered peripherally. The aim of this study was to compare the effects of
      systemic (SI) and pre-portal (PI) insulin administration on energy, glucose and
      protein metabolism in chronic insulin-dependent ketosis-prone diabetic dogs.
      MATERIALS AND METHODS: We applied glucose-controlled insulin infusion, indirect
      calorimetry and stable isotope and radioisotope techniques to measure energy,
      protein and glucose metabolism. We maintained near-normoglycaemia at identical
      levels under both study conditions for 20 h. RESULTS: SI was associated with
      lower oxygen consumption (130+/-13 vs 161+/-8 ml/min), CO(2) production (99+/-10
      vs 130+/-8 ml/min), respiratory quotient (0.76+/-0.02 vs 0.81+/-0.01) and energy
      expenditure (870+/-90 vs 1089+/-60 kcal/24 h) (p<0.05 for all differences). PI
      increased the respiratory quotient from the insulin-deprived state, whereas SI
      did not. Glucose kinetics were similar for SI and PI, whereas leucine oxidation
      (36+/-4 vs 54+/-5 micromol kg(-1) min(-1)) and the fractional synthesis rates of
      liver tissue protein (0.68+/-0.6 vs 0.83+/-0.07%/h), albumin (0.55+/-0.06 vs
      0.68+/-0.4%/h), and fibrinogen (1.73+/-0.23 vs 2.59+/-0.25%/h) were all lower
      during SI than PI (p<0.05). CONCLUSIONS/INTERPRETATION: The route of insulin
      administration did not alter glucose metabolism but did affect protein synthesis
      in the liver. The potential impact of this altered liver protein metabolism on
      chronic complications needs careful evaluation. A similar decrease in energy
      expenditure resulting from systemic insulin administration during tight glycaemic
      control is a potential cause of weight gain.

PMID- 16447054
TI  - Excess mortality in incident cases of diabetes mellitus aged 15 to 34 years at
      diagnosis: a population-based study (DISS) in Sweden.
AB  - AIMS/HYPOTHESIS: The objective of the study was to analyse the mortality,
      survival and cause of death patterns in incident cases of diabetes in the 15-34
      year age group that were reported to the nationwide prospective Diabetes
      Incidence Study in Sweden (DISS). MATERIALS AND METHODS: During the study period
      1983-1999, 6,771 incident cases were reported. Identification of deaths was made
      by linking the records to the nationwide Cause of Death Register. RESULTS: With
      an average follow-up of 8.5 years, resulting in 59,231 person-years, 159 deaths
      were identified. Diabetes was reported as the underlying cause of death in 51
      patients (32%), and as a contributing cause of death in another 42 patients
      (26%). The standardised mortality ratio (SMR) was significantly elevated (RR=2.4;
      95% CI: 2.0-2.8). The SMR was higher for patients classified by the reporting
      physician as having type 2 diabetes at diagnosis than for those classified as
      type 1 diabetic (2.9 and 1.8, respectively). Survival analysis showed significant
      differences in survival curves between males and females (p=0.0003) as well as
      between cases with different types of diabetes (p=0.005). This pattern was also
      reflected in the Cox regression model showing significantly increased hazard for
      males vs females (p=0.0002), and for type 2 vs type 1 (p=0.015) when controlling
      for age. CONCLUSIONS/INTERPRETATION: This study shows a two-fold excess mortality
      in patients with type 1 diabetes and a three-fold excess mortality in patients
      with type 2 diabetes. Thus, despite advances in treatment, diabetes still carries
      an increased mortality in young adults, even in a country with a good economic
      and educational patient status and easy access to health care.

PMID- 16447055
TI  - Diabetes quantitative trait locus research: from physiology to genetics and back.

PMID- 16447056
TI  - Exendin-4, but not glucagon-like peptide-1, is cleared exclusively by glomerular
      filtration in anaesthetised pigs.
AB  - AIMS/HYPOTHESIS: The insulinotropic hormone, glucagon-like peptide-1 (GLP-1), is
      rapidly degraded in vivo as a result of the combination of extensive enzymatic
      degradation and renal extraction. The GLP-1 receptor agonist, exendin-4, has a
      longer duration of action, and has recently been approved as a new agent for the
      treatment of type 2 diabetes mellitus. Exendin-4 is less prone to enzymatic
      degradation, but it is still unclear what other factors contribute to the
      increased metabolic stability. MATERIALS AND METHODS: The overall metabolism of
      GLP-1 and exendin-4 was directly compared in anaesthetised pigs (n=9). RESULTS:
      Metabolism of GLP-1 (C-terminal RIA; t (1/2) 2.0+/-0.2 min, metabolic clearance
      rate [MCR] 23.2+/-2.8 ml min(-1) kg(-1); N-terminal RIA; t (1/2) 1.5+/-0.2 min,
      MCR 88.1+/-10.6 ml min(-1) kg(-1)) was significantly faster than the metabolism
      of exendin-4 (t (1/2) 22.0+/-2.1 min, p<0.0001; MCR 1.7+/-0.3 ml min(-1) kg(-1),
      p<0.01). Differences in arteriovenous concentrations revealed organ extraction of
      GLP-1 by the kidneys (C-terminal 56.6+/-2.6%; N-terminal 48.3+/-5.9%), liver (N
      terminal 41.4+/-3.8%), and peripheral tissues (C-terminal 42.3+/-6.0%; N-terminal
      33.0+/-7.8%), whereas organ extraction of exendin-4 was limited to the kidneys
      (21.3+/-4.9%). While the renal extraction of exendin-4 (6.9+/-2.5 pmol/min) did
      not differ significantly from the amount undergoing glomerular filtration (8.4+/
      2.0 pmol/min), the renal extraction of C-terminal GLP-1 (9.0+/-1.1 pmol/min),
      exceeded the amount which could be accounted for by glomerular filtration (4.2+/
      0.5 pmol/min, p<0.0005). CONCLUSIONS/INTERPRETATION: In addition to an increased
      resistance to enzymatic degradation, the increased stability of exendin-4 is the
      result of reduced differential organ extraction compared to GLP-1. The data
      suggest that in the anaesthetised pig, extraction occurs only in the kidney and
      can be fully accounted for by glomerular filtration.

PMID- 16447057
TI  - Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride
      concentrations and lowers levels of non-esterified fatty acids in humans.
AB  - AIMS/HYPOTHESIS: Diabetic dyslipidaemia contributes to the excess morbidity and
      mortality in patients with type 2 diabetes. Exogenous glucagon-like peptide 1
      (GLP-1) lowers postprandial glycaemia predominantly by slowing gastric emptying.
      Therefore, the effects of GLP-1 on postprandial lipid levels and gastric emptying
      were assessed. METHODS: 14 healthy male volunteers were studied with an i.v.
      infusion of GLP-1 (1.2 pmol kg(-1) min(-1)) or placebo over 390 min in the
      fasting state. A solid test meal was served and gastric emptying was determined
      using a (13)C-labelled sodium octanoate breath test. Venous blood was drawn
      frequently for measurement of glucose, insulin, C-peptide, glucagon, GLP-1,
      triglycerides and NEFA. RESULTS: GLP-1 administration lowered fasting and
      postprandial glycaemia (p<0.0001). Gastric emptying was delayed by GLP-1 compared
      with placebo (p<0.0001). During GLP-1 administration, insulin secretory responses
      were higher in the fasting state but lower after meal ingestion. After meal
      ingestion, triglyceride plasma levels increased by 0.33+/-0.14 mmol/l in the
      placebo experiments (p<0.0001). In contrast, the postprandial increase in
      triglyceride levels was completely abolished by GLP-1 (change in triglycerides, 
      0.023+/-0.045 mmol/l; p<0.05). During GLP-1 infusion, plasma concentrations of
      NEFA were suppressed by 39% in the fasting state (p<0.01) and by 31+/-5% after
      meal ingestion (p<0.01). CONCLUSIONS/INTERPRETATION: GLP-1 improves postprandial
      lipidaemia, presumably as a result of delayed gastric emptying and insulin
      mediated inhibition of lipolysis. Thus, by lowering both glucose and lipid
      concentrations, GLP-1 administration may reduce the cardiovascular risk in
      patients with type 2 diabetes.

PMID- 16447058
TI  - Gamma-aminobutyric acid up- and downregulates insulin secretion from beta cells
      in concert with changes in glucose concentration.
AB  - AIMS/HYPOTHESIS: The role of gamma-aminobutyric acid (GABA) and A-type GABA
      receptors (GABA(A)Rs) in modulating islet endocrine function has been actively
      investigated since the identification of GABA and GABA(A)Rs in the pancreatic
      islets. However, the reported effects of GABA(A)R activation on insulin secretion
      from islet beta cells have been controversial. METHODS: This study examined the
      hypothesis that the effect of GABA on beta cell insulin secretion is dependent on
      glucose concentration. RESULTS: Perforated patch-clamp recordings in INS-1 cells
      demonstrated that GABA, at concentrations ranging from 1 to 1,000 micromol/l,
      induced a transmembrane current (I(GABA)) which was sensitive to the GABA(A)R
      antagonist bicuculline. The current-voltage relationship revealed that I(GABA)
      reversed at -42+/-2.2 mV, independently of glucose concentration. Nevertheless,
      the glucose concentration critically controlled the membrane potential (V (M)),
      i.e., at low glucose (0 or 2.8 mmol/l) the endogenous V (M) of INS-1 cells was
      below the I(GABA) reversal potential and at high glucose (16.7 or 28 mmol/l), the
      endogenous V (M) of INS-1 cells was above the I(GABA) reversal potential.
      Therefore, GABA dose-dependently induced membrane depolarisation at a low glucose
      concentration, but hyperpolarisation at a high glucose concentration. Consistent
      with electrophysiological findings, insulin secretion assays demonstrated that at
      2.8 mmol/l glucose, GABA increased insulin secretion in a dose-dependent fashion
      (p<0.05, n=7). This enhancement was blocked by bicuculline (p<0.05, n=4). In
      contrast, in the presence of 28 mmol/l glucose, GABA suppressed the secretion of
      insulin (p<0.05, n=5). CONCLUSIONS/INTERPRETATION: These findings indicate that
      activation of GABA(A)Rs in beta cells regulates insulin secretion in concert with
      changes in glucose levels.

PMID- 16447060
TI  - Major quantitative trait locus on chromosome 2 for glucose tolerance in diabetic
      SMXA-5 mouse established from non-diabetic SM/J and A/J strains.
AB  - AIMS/HYPOTHESIS: The SMXA-5 mouse is one of the SMXA recombinant inbred
      substrains established from the non-diabetic SM/J and A/J strains, and is a model
      for polygenic type 2 diabetes, characterised by moderately impaired glucose
      tolerance and hyperinsulinaemia. These diabetic traits are worsened by feeding a
      high-fat diet. The aim of this study was to dissect the diabetogenic loci in the
      A/J regions of the SMXA-5 genome that contribute to diabetes-related traits.
      MATERIALS AND METHODS: We analysed the quantitative trait loci (QTL) for diabetes
      related traits and obesity in (SM/JxSMXA-5)F(2) intercross mice fed a high-fat
      diet. To verify the function of the responsible locus that was mapped in the
      present study, we constructed a congenic strain and characterised its diabetes
      related traits. RESULTS: A major QTL for glucose tolerance, free-fed blood
      glucose concentration and BMI was mapped on chromosome 2. This locus existed near
      D2Mit15, with the highest logarithm of the odds score (12.6) for glucose
      concentration at 120 min in a glucose tolerance test, and was designated T2dm2sa.
      The diabetogenic allele of T2dm2sa originated in the A/J strain. SM.A-T2dm2sa, a
      congenic strain that introgressed the T2dm2sa region of A/J genome into SM/J,
      exhibited overt impaired glucose tolerance and hyperinsulinaemia.
      CONCLUSIONS/INTERPRETATION: The development of impaired glucose tolerance in SM.A
      T2dm2sa mice confirmed the results of QTL analysis for diabetes-related traits in
      F(2) intercross mice. The present results suggest that there are latent
      diabetogenic loci in the genomes of non-diabetic A/J and SM/J mice, and that the
      coexistence of these loci, including T2dm2sa, causes impaired glucose tolerance
      in SMXA-5 and SM.A-T2dm2sa mice.

PMID- 16447059
TI  - Cyclooxygenase-2 (PTGS2) inhibitors augment the rate of hexose transport in L6
      myotubes in an insulin- and AMPKalpha-independent manner.
AB  - AIMS/HYPOTHESIS: Some cyclooxygenase-2 (COX2, also known as prostaglandin
      endoperoxide synthase 2 [PTGS2]) inhibitors have been shown to increase insulin
      sensitivity in man or induce hypoglycaemic episodes when overconsumed or taken in
      combination with oral hypoglycaemic drugs. These side-effects and their impact on
      patients are not always recognised in routine clinical practice. We investigated
      whether these side-effects of COX2 (PTGS2) inhibitors result from stimulation of
      the glucose transport system in skeletal muscle cells. MATERIALS AND METHODS: L6
      myotube cultures were used to study effects of COX2 (PTGS2) inhibitors on the
      glucose transport system and their relationship to PTGS2 expression, insulin
      action and AMP-activated protein kinase alpha (AMPKalpha) activity. RESULTS: The
      inhibitors niflumic acid, nimesulide and rofecoxib increased the rate of hexose
      uptake in L6 myotubes in the absence of insulin and in a dose- and time-dependent
      manner. They did this by increasing the total cell content of member 4 of the
      solute carrier family 2 (SCLC2A4, previously known as glucose transporter 4
      [GLUT4]) (but not SCLC2A1 [previously known as GLUT1]) mRNA and protein and the
      amount of it in the plasma membrane. AMPKalpha was not involved in the latter
      effect since the inhibitors did not activate it. In addition, none of the
      inhibitors modulated the rate of hexose transport in vascular endothelial and
      smooth muscle cells expressing PTGS2 and SCLC2A1. Prostaglandin-endoperoxide
      synthase 1 (also known as cyclooxygenase 1) inhibitors (acetylsalicylic acid and
      indomethacin) did not alter the rate of hexose uptake and SCLC2A4 subcellular
      distribution in L6 myotubes. CONCLUSIONS/INTERPRETATION: This study suggests that
      certain COX2 (PTGS2) inhibitors can alter glucose homeostasis in vivo by
      stimulating glucose uptake in skeletal muscles that express PTGS2.

PMID- 16447062
TI  - Evaluation of the immunochromatographic CORIS Giardia-Strip test for rapid
      diagnosis of Giardia lamblia.
AB  - The aim of this study was to evaluate the performance of the CORIS Giardia-Strip
      test (CORIS Bioconcept, Gembloux, Belgium) as a rapid initial method for the
      routine diagnosis of giardiasis. Compared to a commercial ELISA-coproantigen test
      (ProSpect Giardia-ELISA-microplate assay; Remel, Lenexa, KS, USA), the commercial
      strip test had a sensitivity of 58%, a specificity of 99%, a positive predictive
      value of 93% and a negative predictive value of 93% (n=158). These results are
      comparable to those obtained using microscopy of direct wet-mounted stool. Since
      the CORIS Giardia-Strip test is simpler to perform, it can replace direct wet
      mounted stool microscopy for the rapid diagnosis of giardiasis; however, its
      sensitivity is inferior to that of other immunochromatographic antigen detection
      tests and fresh stool samples are required for its use. Nevertheless, the results
      suggest that a positive CORIS Giardia-Strip test outcome does not need
      confirmation, while samples with negative results should be re-examined using
      another, more sensitive, test.

PMID- 16447061
TI  - Vitamin D receptor gene polymorphism in rheumatoid arthritis and associated
      osteoporosis.
AB  - Rheumatoid arthritis (RA) is commonly associated with decreased bone mineral
      density (BMD) due to numerous factors. BsmI polymorphism of the vitamin D
      receptor (VDR) gene has been implicated in the pathogenesis of osteoporosis.
      Vitamin D has several immunomodulatory effects and thus may play a role in the
      course of arthritis. However, little data is available on the possible
      relationship between RA and VDR gene polymorphisms. In this study, the frequency
      of BsmI polymorphism genotypes were compared with that found in other countries.
      In this study, 64 RA patients and 40 healthy controls were tested for VDR gene
      BsmI polymorphism genotypes. Frequencies of B and b alleles were associated with
      markers of bone metabolism and RA. Among control subjects, the frequency of the
      BB genotype is relatively high (27.5%). In RA with secondary
      osteopenia/osteoporosis the BB genotype was more rare, the bb was more common
      than in control subjects. Markers of bone metabolism were associated with the B
      allele. RA patients carrying the B allele had lower BMD and increased bone loss
      over 1 year. The B allele was also correlated with increased osteoclast and
      osteoblast function, as determined by the assessment of biochemical markers of
      bone metabolism. Rheumatoid factor titer, which is an independent marker for
      disease progression in RA, was higher in bb patients. Our data suggest, that the
      imbalance in B and b allele expression may be involved in the pathogenesis of RA
      associated osteoporosis. The possible involvement of vitamin D and VDR gene
      polymorphisms in the development and progression of RA needs further elucidation.

PMID- 16447063
TI  - The partial dopamine D2-like receptor agonist terguride functions as an agonist
      in preweanling rats after a 5-day reserpine regimen.
AB  - RATIONALE: Treating children and adolescents with partial D2-like agonists is
      becoming increasingly common, although few developmental animal studies have
      assessed the psychopharmacology of this class of drug. Contrary to results from
      adult rat studies, it has been reported that partial D2-like agonists may not
      induce agonist-like behavioral effects in preweanling rats during states of low
      dopaminergic tone. OBJECTIVE: The purpose of the present study was to determine
      whether a partial D2-like agonist would act as an agonist in preweanling rats
      after a 5-day regimen of the dopamine-depleting agent reserpine or the tyrosine
      hydroxylase inhibitor alpha-methyl-DL-p-tyrosine (AMPT). METHODS: Sprague-Dawley
      rats were pretreated with reserpine (1 mg kg(-1) per day) or AMPT (3 x 200 mg kg(
      1) per day) on postnatal day (PD) 16-PD 20. Either 2 h (AMPT) or 5 h (reserpine)
      after the last pretreatment injection, rats were treated with saline, the partial
      D2-like agonist terguride, or the full D2-like agonist R(-)-propylnorapomorphine
      (NPA). Distance traveled and repetitive motor movements were measured for 60 min.
      RESULTS: After repeated reserpine treatment, both terguride and NPA increased the
      distance-traveled scores of preweanling rats; however, only NPA, but not
      terguride, increased distance-traveled scores after a 5-day regimen of AMPT or an
      acute injection of reserpine. CONCLUSIONS: It is now apparent that partial D2
      like agonists are capable of inducing agonist-like behavioral effects in
      preweanling rats during a state of low dopaminergic tone. For agonistic actions
      to be observed, the pretreatment regimen must result in substantial and prolonged
      dopamine depletion.

PMID- 16447064
TI  - Comparison of the accumulation of (137)Cs and (90)Sr by six spring wheat
      varieties.
AB  - The uptake of (137)Cs and (90)Sr by six varieties of spring wheat (Triticum
      aestivum) was compared in field trials on land contaminated by the Chernobyl
      accident. All the experimental varieties are officially adopted for agricultural
      use in Belarus and are used in large-scale production. Under identical conditions
      of nutrition, the productivity of the varieties varied significantly by a factor
      of 1.3. The extent of (137)Cs and (90)Sr accumulation by wheat grain, quantified
      as the concentration ratio, differed between the varieties by as much as a factor
      of 1.6, for both radionuclides. There was a significant linear positive
      correlation between the (90)Sr activity concentration in grain and straw, and the
      calcium concentration. The correlation between (137)Cs and potassium was not
      significant. The results suggest that certain varieties of spring wheat used in
      normal agricultural practice accumulate less (137)Cs and (90)Sr into grain than
      others. Some spring wheat varieties accumulated relatively less (137)Cs, but did
      not accumulate less (90)Sr. One variety, Quattro, had a significantly lower
      uptake of both (90)Sr (for grain) and (137)Cs (for both grain and straw) than
      that of the other varieties tested. The reduction efficiency achieved by the use
      of these varieties, however, is not as high as that achieved by soil amelioration
      techniques in the past. Nevertheless, since there are no additional costs or
      production losses associated with these varieties, their use in the contaminated
      areas is worth considering as a simple, practical, and effective contribution to
      reducing the uptake of both (90)Sr and (137)Cs and allowing farmers to produce
      food-grade grain.

PMID- 16447065
TI  - Phosphaturic mesenchymal tumor (mixed connective tissue variant): a case report
      with spectral analysis.
AB  - We present a further case of a rare mesenchymal neoplasm termed phosphaturic
      mesenchymal tumor (mixed connective tissue variant). The patient was a 42-year
      old man with a long history of osteomalacia of unknown etiology with pathological
      bone fracture, abnormality of parathyroid glands, kyphosis, scoliosis, and
      spondylosis. Laboratory investigation disclosed hypophosphatemia, elevated serum
      alkaline phosphatase activity, and normal serum calcium level. The patient had a
      soft tissue mass in the right inguinal area, measuring 11 x 6 x 5 cm, which was
      previously interpreted as a calcified hematoma on sonography. The tumor was
      surgically removed. Grossly, the tumor was well circumscribed, unencapsulated,
      and had soft to dense consistency. The cut surface had a variegated appearance
      due to the presence of large hemorrhagic areas admixed with foci of grey-yellow
      tissue. Histologically, the tumor was composed of primitive mesenchymal cells,
      osteoclast-like cells, and cells showing myofibroblastic features without
      cytologic atypia. There were a well developed vascular network, microcystic
      areas, and poorly formed cartilaginous foci. Unusual and hitherto unpublished
      prominent features were flower-like, slate-gray crystals, widespread hemosiderin
      deposits and large areas of hemorrhages, with the latter comprising approximately
      60% of the tumor. A spectral analysis indicated that chemically, the crystals
      mainly consisted of calcium phosphate and sodium nitrate.

PMID- 16447066
TI  - Natural history of the Nihon (Bhd gene mutant) rat, a novel model for human Birt
      Hogg-Dube syndrome.
AB  - In the Nihon rat, an established model of hereditary renal cell carcinoma (RCC),
      the propensity for tumor development, is inherited as an autosomal dominant trait
      due to a single germline nucleotide insertion mutation in the rat Bhd ortholog.
      The Birt-Hogg-Dube (BHD) syndrome is a rare autosomal dominant disease
      characterized by fibrofolliculoma, pulmonary cysts, spontaneous pneumothorax, and
      renal neoplasm. The renal lesions of the Nihon rat are characterized, and
      extrarenal lesions are also described in this work. The earliest lesion of the
      RCC was identified as an altered tubule at as early as 3 weeks of age and rapidly
      progressed through adenoma to carcinoma with the primary cell type being
      clear/acidophilic where some similarities were evident to RCCs in BHD syndrome.
      The Nihon rats demonstrate a heterotopic ossification within RCCs and three
      extrarenal lesions, clear cell hyperplasia/adenoma of the endometrium, clear cell
      change of the epithelium of striated portions of salivary glands, and cardiac
      rhabdomyomatosis. This rat model of hereditary RCC provides a useful tool for
      analyzing the series of events leading to renal tumorigenesis and for studying
      BHD gene functions.

PMID- 16447067
TI  - A newborn mouse Cryptosporidium parvum infection model: its application to the
      study of therapeutic and prophylactic measures for controlling cryptosporidiosis
      in ruminants.
AB  - In this study, a newborn mouse model of Cryptosporidium parvum infection is
      presented so as to evaluate therapeutic and prophylactic measures for controlling
      cryptosporidiosis in ruminants. Ninety-six suckling mice from ten litters were
      used. The mice in group I were infected with C. parvum oocysts, and the mice in
      group II served as non-infected controls. In both groups, intensity of infection
      and serum IgG, IgA and IgM responses were measured at 6, 9, 12 and 16 days post
      infection (pi). Experimentally induced infection in mice proved to be similar to
      natural infections in lambs, kids and calves. Thus, the intensity of infection
      peaked at 9 days pi then decreased slightly, showing its lowest value at 16 days
      pi. This decline in the number of oocysts coincided with peaks in IgM and IgA.
      Finally, non-infected mice had no oocysts and did not show any increase in their
      anti-C. parvum antibody levels.

PMID- 16447068
TI  - Infectivity for mice of Trypanosoma cruzi I and II strains isolated from
      different hosts.
AB  - In this paper, the infectivity for mice of Trypanosoma cruzi I and II strains
      isolated from sylvatic animals, triatomines, and humans is determined using fresh
      blood examination, hemoculture, culture of macerated organs, and polymerase chain
      reaction (PCR). Six strains were considered to have low infectivity (9.1-18.2%),
      five medium (27.3-45.4%), and one high (100.0%). Infectivity of T. cruzi strains
      isolated from sylvatic animals was significantly higher than that of strains
      isolated from humans and triatomines (p=0.0141). No significant difference was
      observed between the infectivity of T. cruzi I and II strains. The parasite was
      detected by fresh blood examination in one strain, by hemoculture and culture of
      macerated organs in four strains, and by PCR in all strains. We conclude that the
      infectivity is related to the host from which the strains were isolated, but the
      infectivity is not related to the genetic group of the parasite. We also conclude
      that the majority of the strains studied have low and medium infectivity for
      mice, and that PCR is an important tool to detect T. cruzi in strains with this
      biological characteristic.

PMID- 16447070
TI  - Characterization of a mercury-reducing Bacillus cereus strain isolated from the
      Pulicat Lake sediments, south east coast of India.
AB  - Pulicat Lake sediments are often severely polluted with the toxic heavy metal
      mercury. Several mercury-resistant strains of Bacillus species were isolated from
      the sediments and all the isolates exhibited broad spectrum resistance
      (resistance to both organic and inorganic mercuric compounds). Plasmid curing
      assay showed that all the isolated Bacillus strains carry chromosomally borne
      mercury resistance. Polymerase chain reaction and southern hybridization analyses
      using merA and merB3 gene primers/probes showed that five of the isolated
      Bacillus strains carry sequences similar to known merA and merB3 genes. Results
      of multiple sequence alignment revealed 99% similarity with merA and merB3 of
      TnMERI1 (class II transposons). Other mercury resistant Bacillus species lacking
      homology to these genes were not able to volatilize mercuric chloride, indicating
      the presence of other modes of resistance to mercuric compounds.

PMID- 16447069
TI  - The anti-amoebic activity of some medicinal plants used by AIDS patients in
      southern Thailand.
AB  - The anti-amoebic activities of chloroform, methanol and water extracts from 12
      Thai medicinal plants (39 extracts) commonly used by AIDS patients in southern
      Thailand were screened, at a concentration of 1,000 microg/ml, against Entamoeba
      histolytica strain HTH-56:MUTM and strain HM1:IMSS growing in vitro. The extracts
      were incubated with 2x10(5) E. histolytica trophozoites/ml of medium at 37
      degrees C under anaerobic conditions for 24 h. The cultures were examined with an
      inverted microscope and scored (1-4) according to the appearance and numbers of
      the trophozoites. The extracts that caused inhibition were selected and retested
      using the same conditions but with concentrations that ranged from 31.25 to 1,000
      microg/ml using E. histolytica strain HM1:IMSS, and the IC(50) values for each
      extract were calculated. The chloroform extracts from Alpinia galanga (IC(50)
      55.2 microg/ml), Barleria lupulina (IC(50) 78.5 microg/ml), Boesenbergia
      pandurata (IC(50) 45.8 microg/ml), Piper betle (IC(50) 91.1 microg/ml) and Piper
      chaba (IC(50) 71.4 microg/ml) and the methanol extract from B. pandurata (IC(50)
      57.6 microg/ml) were all classified as "active", i.e. with an IC(50) of less than
      100 microg/ml, whereas those from Murraya paniculata (IC(50) 116.5 microg/ml) and
      Zingiber zerumbet (IC(50) 196.9 microg/ml) were classified as being "moderately
      active". The IC(50) of a standard drug, metronidazole, was 1.1 microg/ml.

PMID- 16447071
TI  - The alpha-tubulin gene AmTuba1: a marker for rapid mycelial growth in the
      ectomycorrhizal basidiomycete Amanita muscaria.
AB  - The apical extension of hyphae is of central importance for extensive spread of
      fungal mycelium in forest soils and for effective ectomycorrhiza development.
      Since the tubulin cytoskeleton is known to be important for fungal tip growth, we
      have investigated the expression of an alpha-tubulin gene from the
      ectomycorrhizal basidiomycete Amanita muscaria (AmTuba1). The phylogenetic
      analysis of protein sequences revealed the existence of two subgroups of alpha
      tubulins in homobasidiomycetes, clearly distinguishable by defined amino acids.
      AmTuba1 belongs to subgroup1. The AmTuba1 transcript level is related to mycelial
      growth rate. Growth induction of carbohydrate starved (non-growing) hyphae
      resulted in an enhanced AmTuba1 expression as soon as hyphal growth started,
      reaching a maximum at highest mycelial growth rate. Bacterium-induced hyphal
      elongation also leads to increased AmTuba1 transcript levels. In mature A.
      muscaria/P. abies ectomycorrhizas, where fungal hyphae are highly branched, and
      slowly growing, AmTuba1 expression were even lower than in carbohydrate-starved
      mycelium, indicating a further down-regulation of gene expression in symbiosis.
      In conclusion, our analyses show that the AmTuba1 gene can be used as a marker
      for active apical extension in fly agaric, and that alpha-tubulin proteins are
      promising tools for the classification of fungi.

PMID- 16447072
TI  - Management of cystic lymphangioma in children: experience in Jos, Nigeria.
AB  - The management of cystic lymphangiomas (CL), especially in the head and neck
      region, presents challenges to the pediatric surgeon. This is a retrospective
      study of all children seen with lymphangioma at the Pediatric Surgical Unit of
      the Jos University Teaching Hospital from 1996 to 2004. There were 27 children,
      14 (51.9%) were males and 13 (48.1%) were females (M:F = 1.2:1), with ages
      ranging from 2 days to 5 years (median 5 months). Majority (84.6%) of the
      patients were below 1 year. The head and neck region was the most frequent site
      of involvement. There were three cases of lymphangioma circumscriptum. Six
      (54.5%) of the 11 children with cervical CL presented with complications
      including infection in 4, respiratory obstruction in 3, ulcerated lesion in 1 and
      intracystic hemorrhage with rapid increase in cyst size in 1. Twenty-three
      children had either surgical excision or marsupialization. The main complications
      were wound infections and respiratory obstructions, which led to five deaths. Six
      children had recurrences, some of which occurred at sites which were normal at
      the initial or previous excision. The mortality rate was high (34.8%), mainly due
      to respiratory obstruction and asphyxia in the head and neck lesions. Head and
      neck region was the most commonly involved site by CL. The management of CL at
      this site is associated with significant morbidity and a high rate of mortality.

PMID- 16447073
TI  - Differential expression of potassium currents in Deiters cells of the guinea pig
      cochlea.
AB  - Among the supporting cells, Deiters cells are in intimate contact with outer hair
      cells (OHCs) in the inner ear. The aim of this study was to characterize the
      outward rectifying K+ current of Deiters cells in conjunction with cellular
      morphological characteristics. In the majority of cells, the K+ current had a
      biphasic inactivation kinetics (tau1 and tau2 were 2,735+/-90 (n=77) and 160+/-14
      ms (n=72), respectively). The rapidly inactivating current component was more
      sensitive to Charybdotoxin (ChTx, 10 nM) block whereas the slowly inactivating
      current could be blocked more efficiently by tetraethylammonium (1 mM). All these
      point toward the existence of two distinct potassium channel types in these
      cells. Deiters cells attached to shorter OHCs had more voluminous, whereas those
      attached to longer OHCs had lanky cell bodies. The inactivation kinetics was
      slower in cells having corpulent cell bodies due to the increased proportion of
      the slowly inactivating current component (0.736+/-0.033, n=27) as compared to
      the one determined for lanky cells (0.522+/-0.023, n=36). The average peak K+
      current was higher in Deiters cells connected to OHCs (5,417+/-541 pA, n=40) than
      in isolated ones (3,527+/-410, n=37). Deiters cells having different cell shapes
      and showing different K+ channel expression may contribute to the active
      mechanism of the cochlea to various degrees.

PMID- 16447074
TI  - Effects of bacteriophages on free radical production and phagocytic functions.
AB  - Reactive oxygen species (ROS) play a major role in mediating antibacterial
      functions of phagocytic cells. However, excessive ROS production may cause
      oxidative stress and tissue damage. Uncompensated ROS release has been implicated
      in a variety of disorders. Novel means of controlling elevated ROS production are
      urgently needed. We showed that homologous but not the heterologous phages
      inhibited, in a dose dependent manner, the degree of chemiluminescence in
      phagocytes induced by Escherichia coli. Treatment of the cells with the phages
      alone resulted in a small increase in ROS production. Homologous phages also
      facilitated phagocytosis when preincubated with bacteria. On the other hand, both
      homologous and heterologous phages inhibited phagocytosis following preincubation
      with phagocytic cells. The treatment of infected and uninfected mice with phages
      did not significantly alter the rate of phagocytosis by blood granulocytes and
      monocytes. In conclusion, we showed that bacteriophages can decrease ROS
      production by phagocytes. Although in some in vitro experimental models the
      phages tended to diminish phagocytosis, this phenomenon may be of little
      significance in clinical situations, since the process of eliminating bacteria in
      phage-treated patients is predominantly accomplished by both phages and
      phagocytes.

PMID- 16447075
TI  - International symposium: "Modern technologies in thyroid surgery", 10-11 February
      2006, Halle/s., Germany. Abstracts.

PMID- 16447076
TI  - Bilateral renal lymphangiomatosis mimicking hydronephrosis: multidetector CT
      urographic findings.
AB  - Renal lymphangiomatosis is a very rare disorder, with only a few reported cases.
      We present a case of bilateral renal lymphangiomatosis, manifested by bilateral
      flank pain, that was falsely diagnosed as hydronephrosis. Excretory urographic,
      ultrasonographic, and computed tomographic urographic findings are described.

PMID- 16447077
TI  - Functional renal imaging: nonvascular renal disease.
AB  - Functional renal imaging-a fast-growing field of MR-imaging-applies different
      sequence types to gather information about the kidneys other than morphology and
      angiography. This update article presents the current status of different
      functional imaging approaches and presents current and potential clinical
      applications. Apart from conventional in-phase and opposed-phase imaging, which
      already yields information about the tissue composition, BOLD (blood-oxygenation
      level dependent) sequences, DWI (diffusion-weighted imaging) sequences, perfusion
      measurements, and dedicated contrast agents are used.

PMID- 16447078
TI  - Scrotal involvement in Madelung disease: clinical, ultrasound and MR findings.
AB  - Multiple symmetrical lipomatosis, also known as Madelung disease, Launois
      Bensaude syndrome, and benign symmetrical lipomatosis, is an uncommon disease
      that is characterized by the presence of multiple and symmetrical deposits of
      nonencapsulated adipose tissue in the neck, upper trunk, arms, and legs. It
      affects mainly men, with a higher incidence in the Mediterranean area, and is
      typically associated with high alcohol consumption and a high prevalence of
      peripheral neuropathy that usually appears long after the development of
      lipomatous masses. We report the case of a patient with involvement of the
      scrotum. We present clinical, ultrasound, and magnetic resonance appearances of
      these scrotal lipomatous masses for the first time.

PMID- 16447079
TI  - Internal fistulas in Crohn disease: magnetic resonance enteroclysis.
AB  - Internal fistulas (IFs) and abscesses are the most common complications of Crohn
      disease (CD). To reliably diagnose and clearly distinguish inflammatory or
      fibrostenotic manifestations of CD from its complications is of paramount
      importance to appropriately guide therapeutic decisions. Magnetic resonance
      enteroclysis (MRE), a recently introduced technique for small bowel imaging, has
      proved a high efficacy in the depiction of luminal and extraluminal
      manifestations of CD and holds great promise as a powerful diagnostic tool in the
      comprehensive diagnostic workup of this disease. As of yet, the characteristic
      imaging appearance of IFs on MRE has not been described in detail. This article
      reviews the performance of conventional imaging techniques and the current
      potential of MRE in the depiction of IFs in CD. Typical imaging morphology and
      characteristic imaging findings of IFs on MRE are described in detail and a newly
      defined and highly indicative imaging finding, the "star-sign," is presented and
      discussed.

PMID- 16447080
TI  - Endovascular repair of abdominal aortic aneurysms: CTA evaluation of
      contraindications.
AB  - Endovascular aortic aneurysm repair (EVAR) is considered an acceptable
      alternative to open surgery in selected patients. Its feasibility depends mainly
      on anatomic factors that represent the important predictors of success and the
      most important exclusion criteria. Poor anatomic patient selection is generally
      associated with a higher risk for procedural complications and compromised long
      term outcomes. Therefore pretreatment imaging is crucial for evaluating patient
      suitability for EVAR. Multidetector computed tomographic angiography represents
      the current standard of reference in the evaluation of the abdominal aorta and
      iliac axis anatomy because it provides all the details needed for selection of
      patients who are suitable for endograft and the choice of the appropriate device.
      This report identifies and reviews computed tomographic angiographic anatomic
      contraindications for EVAR.

PMID- 16447081
TI  - Early ovarian cancer: 3-D power Doppler.
AB  - Transvaginal sonography plays an important role in the assessment of the
      morphology of ovarian lesions. However, the accuracy of the technique is limited
      due to the significant number of false-positive results. Color Doppler imaging
      and pulsed Doppler spectral analysis enable evaluation of ovarian tumor blood
      flow, analysis of the distribution of blood vessels, and quantitative measurement
      of blood flow velocity waveforms. These parameters increase the sensitivity and
      specificity of ultrasound evaluation of ovarian tumors. Unfortunately, there is
      no consensus as to which Doppler parameters and cutoff values are the most
      predictive of malignancy. Three-dimensional (3-D) power Doppler ultrasound
      provides a new tool to evaluate features of tumor vascularity. Three-dimensional
      ultrasound and 3-D power Doppler imaging in patients with "positive" findings on
      standard ultrasound tests, which encompass annual gray-scale transvaginal
      sonography followed by transvaginal color Doppler ultrasound in selected cases,
      represent a novel approach for early and accurate detection of ovarian cancer
      through screening. Combined evaluations of morphology and neovascularity by 3-D
      power Doppler ultrasound may improve early detection of ovarian carcinoma.
      Contrast-enhanced 3-D power Doppler sonography facilitates visualization of
      adnexal tumor vessels, which may aid in differentiating benign from malignant
      adnexal lesions.

PMID- 16447082
TI  - Malignant fibrous histiocytoma of the spleen: report of a case and literature
      review.
AB  - There is a marked paucity of reports on malignant fibrous histiocytoma (MFH) of
      the spleen in the literature, and there are no previous reports of its color
      Doppler sonographic (US) and contrast-enhanced US findings. We report on an 82
      year-old male with splenic MFH (inflammatory subtype), with an emphasis on color
      Doppler and contrast-enhanced US findings.

PMID- 16447083
TI  - Hepatic peliosis (bacillary angiomatosis) in AIDS: CT findings.

PMID- 16447084
TI  - Crohn disease of the small bowel: MR enteroclysis versus conventional
      enteroclysis.
AB  - Enteroclysis has been suggested as the technique of choice for the evaluation of
      Crohn disease of the small intestine. Adequate distention of the entire small
      bowel with barium suspension allows the radiologic demonstration of mucosal
      abnormalities and provides functional information by defining distensibility or
      fixation of the small bowel loops. The principal disadvantage of conventional
      enteroclysis is the limited indirect information on the state of the bowel wall
      and extramural extension of Crohn disease, and its effectiveness may be hindered
      owing to overlapping bowel loops. Moreover, the radiation dose administered to
      patients, mostly at a young age, should be considered. Magnetic resonance (MR)
      enteroclysis is an emerging technique for small bowel imaging and was introduced
      to overcome the limitations of conventional enteroclysis and MR cross-sectional
      imaging by combining the advantages of both into one technique. MR enteroclysis
      has the potential to change how the small bowel is assessed because of the
      functional information, soft tissue contrast, direct multiplanar imaging
      capabilities, and lack of ionizing radiation.

PMID- 16447085
TI  - Imaging of the renal transplant: comparison of MRI with duplex sonography.
AB  - Renal transplantation is an established treatment for patients with end-stage
      renal disease. Many causes of graft dysfunction are treatable, making prompt
      detection and diagnosis of complications essential. Sensitive, noninvasive
      imaging procedures, which do not use iodinated contrast media, are therefore
      highly desirable to evaluate graft function. Duplex sonography (US) has
      traditionally been the initial investigation of graft dysfunction. US offers many
      advantages, particularly during the postoperative period, when it can be
      performed portably regardless of renal function and can guide percutaneous
      procedures. However, US lacks specificity in assessing hydronephrosis, cannot
      differentiate parenchymal causes of dysfunction, and may have difficulty
      assessing transplant vessels. Recently comprehensive magnetic resonance imaging
      (MRI) protocols including MR urography, gadolinium-enhanced MR angiography, and
      MR renography have evolved as a "one-stop" diagnostic technique in the evaluation
      of the entire graft and peritransplant region. Multiplanar capabilities enable
      MRI to identify the site of urinary obstruction and assess renal vessels in their
      entirety. The evolving technique of MR renography may also differentiate
      parenchymal causes of dysfunction. By combining these three components into a
      single examination, further information may be obtained regarding the graft when
      compared with US and other conventional studies, with improved patient
      convenience, less morbidity, and a potential cost saving.

PMID- 16447087
TI  - Transcatheter arterial embolization in the management of hemobilia.
AB  - BACKGROUND: This retrospective analysis evaluated the clinical and radiologic
      results of transcatheter arterial embolization (TAE) in the treatment of
      significant hemobilia. The imaging findings, embolization technique,
      complications, and efficacy are described. METHODS: Thirty-two consecutive
      patients (21 male, 11 female, age range 8-61 years) who were referred to the
      radiology department for severe or recurrent hemobilia were treated by TAE.
      Causes of hemobilia were liver trauma (n = 19; iatrogenic in six and road traffic
      accident in 13), vasculitis (n = 6), vascular malformations (n = 2), and
      hepatobiliary tumors (n = 5). Iatrogenic liver trauma was secondary to
      cholecystectomy in those six patients. Four of five hepatobiliary tumors were
      inoperable malignant tumors and one was a giant cavernous hemangioma. Arterial
      embolization was done after placing appropriate catheters as close as possible to
      the bleeding site. Embolizing materials used were Gelfoam, polyvinyl alcohol
      particles or steel coils, alone or in combination. Postembolization angiography
      was performed in all cases to confirm adequacy of embolization. Follow-up color
      Doppler ultrasound and contrast-enhanced computed tomography was done in all
      patients. RESULTS: Ultrasonic, computed tomographic, and angiographic appearances
      of significant hemobilia were assessed. Angiogram showed the cause of bleeding in
      all cases. Three patients with liver trauma due to accidents required repeat
      embolization. Eight patients required surgery due to failed embolization
      (continuous or repeat bleeding in four patients, involvement of the large
      extrahepatic portion of hepatic artery in two, and coexisting solid organ
      injuries in two). Severity of hemobilia did not correlate with grade of liver
      injury. All 13 patients with blunt hepatic trauma showed the cause of hemobilia
      in the right lobe. No patient with traumatic hemobilia showed an identifiable
      cause in the left lobe. There were no clinically significant side effects or
      complications associated with TAE except one gallbladder infarction, which was
      noted at surgery, and cholecystectomy was performed with excision of the hepatic
      artery aneurysm. CONCLUSION: TAE is a safe and effective interventional
      radiologic procedure in the nonoperative management of patients who have
      significant hemobilia.

PMID- 16447086
TI  - Gallbladder adenoma: report of a case with emphasis on contrast-enhanced US
      findings.
AB  - There is a marked paucity of contrast-enhanced ultrasound (US) findings of
      gallbladder disease in the literature, and there is only one previous case of
      gallbladder adenoma. We report such a case. US showed a 2-cm polypoid lesion at
      the gallbladder body. Color Doppler US showed the hypervascular nature of the
      lesion, and contrast-enhanced US revealed the lesion to be homogeneously
      enhanced, suggesting that the lesion was composed of the same pathology. The
      lesion was surgically resected, and was found to be an adenoma without cancer
      foci. This case suggests that contrast-enhanced US is an effective tool in
      diagnosing a gallbladder adenoma.

PMID- 16447088
TI  - MR imaging of nephropathies.
AB  - Acute and chronic nephropathies are responsible for morphologic and functional
      renal changes. However, radiologic techniques currently play a minor role in
      imaging of parenchymal nephropathies in native or transplanted kidneys. From a
      morphologic point of view, three-dimensional magnetic resonance (MR) volumetric
      biomarkers of kidney function, such as renal and cortical volumes or cystic
      volume, in polycystic kidney diseases play a growing role in nephrologic
      practice. From a functional point of view, if scintigraphic techniques remain the
      major sources of renal performance assessment, new MR imaging systems and
      specific MR contrast agents may soon provide significant developments in the
      evaluation of renal performance (glomerular filtration rate measurement), in the
      search for prognostic factors (hypoxia, inflammation, cell viability, degree of
      tubular function, and interstitial fibrosis), and for monitoring new cell
      therapies. New developments that have provided higher signal-to-noise ratio and
      higher spatial and/or temporal resolutions have the potential to direct new
      opportunities for obtaining morphologic and functional information on tissue
      characteristics that are relevant for various renal diseases with respect to
      diagnosis, prognosis, and treatment follow-up.

PMID- 16447089
TI  - Tumor angiogenesis: pathophysiology and implications for contrast-enhanced MRI
      and CT assessment.
AB  - The process of tumor neoangiogenesis plays a central role in the growth and
      spread of tumors. It is currently a leading theme in oncology, and many new drugs
      targeting the tumor neoangiogenic process are under development. Expanding tumors
      become hypoxic and tumor cells express transcription factors, such as the hypoxia
      inducible factor (HIF), which induce the release of proangiogenic growth factors
      such as vascular endothelial growth factors (VEGF) and transforming growth
      factors that promote the formation of new capillaries by recruiting, activating,
      and stimulating endothelial cells. Activated endothelial cells secrete matrix
      metalloproteases, which degrade the basement membrane and the extracellular
      matrix, and adhesion receptors such as integrins alphavbeta(3), which allow their
      migration into the extracellular matrix toward the tumor cells. The newly grown
      vessels are immature and differ from normal capillaries. They are tortuous and
      irregular, resulting in poorly efficient perfusion, they are leaky (especially to
      macromolecules), and they are independent of the normal mechanisms of regulation
      of the capillary blood flow. Moreover, tumor microcirculation is heterogeneous.
      Evaluation of angiogenesis can be used as a prognostic marker to evaluate the
      aggressiveness of tumor and as a potential predictive marker of antiangiogenic
      treatment response. Histopathologic techniques of microvascular density indexes
      require invasive tissue sampling and need to be standardized. Hemodynamic
      characteristics of immature neovessels can be noninvasively assessed by dynamic
      contrast-enhanced magnetic resonance imaging or computed tomography. Tissue
      enhancement depends on arterial input function, kinetic of distribution of blood
      into the capillary bed, leakage across the capillary walls, and volume of the
      interstitial space. Pharmacodynamic models allow the evaluation of microvascular
      parameters of tissue blood flow, tissue blood volume, tissue interstitial volume,
      mean transit time, and permeability by surface of capillary wall. Methods based
      on dynamic contrast enhancement have been shown to correlate with conventional
      outcome methods such as histopathologic studies and survival. Radiologists must
      be convinced that, by using this emerging and promising approach, it is becoming
      possible to gain functional information during routine tumor imaging.

PMID- 16447090
TI  - PET in abdominal pathology: advantages and limitations.
AB  - New oncologic procedures are currently more focused on the biological features of
      tumors. The ideal objective is the administration of personalized effective
      treatments for each patient that affects not just the location and spread of
      disease but also special metabolic characteristics of tumoral cells. Radiologic
      diagnostic methods are extremely important in the management of the patient for
      staging, restaging, and evaluation of treatment response, and clinicians are avid
      for some additional functional and metabolic information. Further, they need more
      dynamic methods for follow-up. Nuclear Medicine and positron emission tomography
      (PET) in many cases can meet this requirement, although it is not perfect, at
      least at the present time. Currently 2-((18)F)fluoro-2-desoxi-D: -glucose
      positron emission tomography is being widely used for oncologic purposes. Its
      information can be very useful in abdominal diseases and must be taken into
      account with the results of radiologic imaging. Thus, many changes in the choice
      of treatment are seen. However, it is very important to know that sometimes there
      is a lack of specificity that has to be considered.

PMID- 16447091
TI  - Unknown ESUR cases 2004.
AB  - The authors present 14 cases from the film interpretation session of the 11th
      annual meeting of the European Society of Urogenital Radiology presented in
      September, 2004. The cases demonstrate the imaging findings, differential
      diagnoses, and clinical relevance of a wide variety of genitourinary tract
      diseases. The cases include examples of benign and malignant urinary tract
      neoplasms, inflammatory processes, vascular diseases, traumatic injuries, and
      congenital anomalies.

PMID- 16447092
TI  - ESUR guidelines on contrast media.
AB  - Since 1996 the Contrast Media Safety Committee of the European Society of
      Urogenital Radiology has released 15 guidelines regarding safety in relation to
      the use of radiographic, ultrasonographic, and magnetic resonance contrast media.
      The guidelines have been well received by the radiologic community in Europe and
      all over the world and comprise current standards for good practice at many
      institutions. The present report is an overview of the work accomplished by the
      European Society of Urogenital Radiology over the past 8 years. The committee has
      covered renal and nonrenal adverse events and other aspects of contrast media.

PMID- 16447093
TI  - MR colonography in inflammatory bowel disease.
AB  - Colonography based on magnetic resonance imaging (MRI) appears to be a promising
      technique for polyp assessment in the colon. Several studies have evaluated this
      method for colonic assessment in patients with inflammatory bowel disease. We
      briefly review different methodologies such as dark lumen and bright lumen
      techniques for abdominal MRI. In addition, recently published studies concerning
      the sensitivity and accuracy in detecting inflammatory bowel changes in
      inflammatory bowel disease using MRI are discussed.

PMID- 16447094
TI  - MDCT angiography of living laparoscopic renal donors.
AB  - Laparoscopic donor nephrectomy has become the accepted method of harvesting the
      kidney at many institutions because of multiple advantages over open donor
      nephrectomy. Spiral computed tomographic (CT) angiography provides accurate
      information of renal vascular anatomy and has become an accepted method of
      preoperative evaluation of potential laparoscopic renal donors. More recently,
      multidetector CT (MDCT) provides more detailed datasets compared with single
      detector spiral CT and has been used for preoperative evaluation of laparoscopic
      donor nephrectomy to provide accurate anatomic information. MDCT (especially 16-
      and 64-slice MDCT) angiography has advantages over single-detector helical CT due
      to rapid scan time that allows coverage of a large volume of interest with higher
      spatial and temporal resolutions. In this article, we review the current status
      of MDCT angiography in the evaluation of laparoscopic renal donors and potential
      advantages of using this technology.

PMID- 16447095
TI  - Sonoenteroclysis: a new technique for the diagnosis of small bowel diseases.
AB  - BACKGROUND: Radiologic evaluation of small bowel is usually done by barium
      examination, which involves considerable radiation exposure. A new sonographic
      method, sonoenteroclysis, is a promising technique for diagnosing small
      intestinal disorders. In this study the applicability, performance, and
      diagnostic yield of sonoenteroclysis were assessed and the results of this novel
      method were compared with those of barium enteroclysis. METHODS: Forty-five
      consecutive patients with suspected small bowel disorder were studied. All
      patients underwent abdominal ultrasound before and after infusion of an isotonic
      nonabsorbable electrolyte solution containing polyethylene glycol through a
      nasojejunal tube (modified Billbao Dotter tube), and images at various levels
      were obtained. Small bowel wall thickness, luminal narrowing, intestinal
      dilatation, peristalsis, and extraintestinal complications were noted. It was
      followed by barium enteroclysis and findings were recorded. Findings of
      sonoenteroclysis were compared with those of barium enteroclysis. RESULTS:
      Satisfactory distention of the intestinal lumen was obtained with sequential
      visualization of jejunoileal loops in 34.4 +/- 18.4 min. Of 45 patients, 10
      showed normal small bowel on sonoenteroclysis and barium enteroclysis. These 10
      patients served as controls. Sonoenteroclysis displayed normal diameters smaller
      than 3.0 and 2.0 cm for the jejunum and ileum, respectively. Bowel wall thickness
      was 1.7 to 3.0 mm and all five layers of bowel wall could be well appreciated.
      Valvulae conniventes were clearly visualized with a fold thickness between 1.4
      and 2.0 mm. The remaining 35 patients showed abnormalities in the form of
      strictures, matted bowel loops, dilated loops, thickened folds, deformed
      ileocecal junction, mass lesions, etc., on sonoenteroclysis and barium
      enteroclysis. In addition, sonoenteroclysis showed thickened bowel wall with loss
      of stratification. Extraintestinal findings such as enlarged lymph nodes and
      ascites were also disclosed at the time of sonography. These were diagnosed
      subsequently as cases of tuberculosis (n = 23), celiac disease (n = 6),
      adenocarcinoma (n = 2), leiomyoma (n = 2), Immunoproliferative small intestinal
      disease (n = 1), and segmental enteritis (n = 1). CONCLUSIONS: The diagnostic
      accuracy of sonoenteroclysis for detecting small bowel lesions is comparable to
      that of barium enteroclysis. This new, widely available, inexpensive, and
      undemanding technique can be used as an initial investigation in the evaluation
      of patients with small bowel disorders.

PMID- 16447096
TI  - Abdominal spilled stones: ultrasound findings.
AB  - Laparoscopic cholecystectomy (LC) is the treatment of choice for uncomplicated
      symptomatic gallstones. Spillage of stones due to gallbladder rupture has been
      reported in up to 33% of all LCs, but clinical sequelae caused by dropped
      gallstones are uncommon. We recently observed two patients with retained stones
      after LC. Correct diagnosis was made by abdominal ultrasonography (US) in both
      cases. In the first patient, who presented with fever, malaise, and weight loss
      18 months after LC, abdominal US revealed hypoechoic focal lesions containing
      hyperechoic images with posterior shadowing of the liver and spleen. US-guided
      aspiration biopsies of these lesions yielded purulent material, and the injection
      and aspiration of saline solution provoked rolling movements of the hyperechoic
      images. Laparotomy confirmed the diagnosis of abscess-containing spilled
      gallstones. In the second patient, multiple hyperechoic images with posterior
      shadowing were observed in the Morison pouch during a routine US examination. The
      diagnosis of retained stones was consistent with the history of gallstone
      spillage during LC performed 2 months previously and was confirmed by computed
      tomographic findings of hyperdense images in the Morison pouch. The patient was
      asymptomatic, and treatment was thus deferred. Our experience suggests that US
      can be very useful in the detection of gallstones spilled during LC.

PMID- 16447098
TI  - TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant
      multisystem disorder.
AB  - The TNF-receptor-associated periodic syndrome (TRAPS) is an autosomal dominant
      auto-inflammatory disorder, characterized by recurrent febrile attacks and
      localized inflammation. TRAPS is caused by mutations in the gene encoding the TNF
      Receptor Super Family 1A (TNFRSF1A) on chromosome 12p13. However, the incomplete
      penetrance and genetic heterogeneity have been reported in this syndrome.
      Although the ethnic diversity and clinical heterogeneity may propose the role of
      other genes in the pathogenesis of TRAPS, some low-penetrance TNFRSF1A variants
      contribute to atypical inflammatory responses in other autoimmune diseases.
      Furthermore, molecular studies on TRAPS and other auto-inflammatory disorders
      could be suggested to identify additional genes coding the molecules in the TNF
      signalling process.

PMID- 16447097
TI  - Value of carbon dioxide wedged venography and transvenous liver biopsy in the
      definitive diagnosis of Abernethy malformation.
AB  - We report a 25-year-old man who presented with congenital absence of the portal
      vein, or Abernethy malformation, a rare congenital disorder in which the
      mesenteric and splenic venous drainages bypass the liver and directly drain into
      the inferior vena cava through an extrahepatic portosystemic shunt. Magnetic
      resonance imaging, which showed multiple nodular lesions in both liver lobes that
      were associated with an absence of intrahepatic portal venous branches, strongly
      suggested the diagnosis of the Abernethy malformation. Carbon dioxide wedged
      venography and transvenous liver biopsy, which were performed in the same session
      by a right jugular approach, confirmed these findings. This technique can be
      considered a valuable alternative diagnostic tool to catheter arteriography and
      percutaneous transhepatic liver biopsy.

PMID- 16447099
TI  - Assessing delayed effects of a multi-site system intervention for homeless
      persons with serious mental illness.
AB  - ACCESS demonstration sites were followed for an additional two years beyond the
      scheduled four-year evaluation to assess whether any delayed effects had occurred
      in system and project integration. For system integration, findings indicate that
      there was a sharp increase between Wave 3 (1998) and Wave 4 (2000), but
      experimental and comparison sites had identical trends. For project integration,
      experimental sites at Wave 4 sustained the high level of integration achieved at
      Wave 3, but the comparison sites achieved the same level as the experimental
      sites at Wave 4, through an abrupt increase in their scores. The absence of
      delayed effects is likely due to diffusion of the interventions to comparison
      sites both in the latter stages of the demonstration and immediately afterwards.
      Further, aggressive lobbying on the part of ACCESS program managers to generate
      local and state support to sustain their services following the termination of
      federal funding, had an integrating effect thereby creating linkages among
      comparison site agencies. Implications of these findings for policy and further
      research are highlighted.

PMID- 16447100
TI  - Pregnancy and delivery after in vitro maturation of naked ICSI-GV oocytes with GH
      and transfer of a frozen thawed blastocyst: case report.
AB  - PURPOSE: To determine if GV oocytes, collected at the time of ICSI, can be
      matured in vitro and rescued for therapeutic treatment. A patient for whom all
      the collected oocytes at the GV stage after a classical COH protocol were matured
      in vitro with GH. METHOD: All the naked oocytes were matured in a culture medium
      (ISM2) containing 15% patient serum +1.6 units of GH (Saizen) per millilitre.
      Oocytes were incubated overnight at 37 degrees C. The MII oocytes obtained were
      micro-injected. A fresh transfer was performed and a supernumerary blastocyst was
      frozen. RESULTS: The patient was pregnant and delivered a healthy girl after
      transfer of the frozen/thawed blastocyst. The baby girl is now 2 years old.
      CONCLUSION: In vitro maturation with GH allows rescuing naked GV oocytes
      collected at the time of ICSI. GH action does not pass through the cumulus cells.
      According to the possible lack of synchrony between the embryo and the uterus, we
      recommend to freeze the embryos obtained and to replace them in a controlled
      cycle.

PMID- 16447101
TI  - Lactobacillus bacteremia, species identification, and antimicrobial
      susceptibility of 85 blood isolates.
AB  - BACKGROUND: Data regarding antimicrobial susceptibility of clinical Lactobacillus
      isolates are scarce, and appropriate interpretation criteria for susceptibility
      tests are not available. METHODS: We examined 85 cases of Lactobacillus
      bacteremia, of which 47 cases have been included in our previous studies.
      Overall, 14 antimicrobial agents were evaluated by the E-test method, and these
      results were compared with disk diffusion test findings. The clinical outcomes of
      the patients and their antimicrobial treatments were registered. RESULTS: The
      antimicrobial susceptibility of Lactobacillus strains was species dependent. The
      considerable number of Lactobacillus rhamnosus (n=46), Lactobacillus fermentum
      (n=12), and Lactobacillus casei (n=12) strains available for testing made it
      possible to compare the susceptibilities within 1 species, as well. Of the 46 L.
      rhamnosus isolates, 22 were identified as L. rhamnosus GG type by pulsed-field
      gel electrophoresis. All Lactobacillus isolates demonstrated low minimum
      inhibitory concentrations (MICs) of imipenem, piperacillin-tazobactam,
      erythromycin, and clindamycin. MICs of vancomycin were high (>256 microg/mL) for
      all other species except Lactobacillus gasseri and Lactobacillus jensenii. Disk
      diffusion and E-test results were concordant. The MICs of cephalosporins varied;
      cefuroxime demonstrated a higher level of activity than did ceftriaxone.
      Benzylpenicillin and ampicillin MICs had variable ranges between different
      species. Combination therapy was given to 83% of the patients, but, in 54% of
      them, therapy included only 1 microbiologically active agent, according to
      results of the susceptibility tests. Mortality at 1 week was 12% among patients
      who presumably were receiving adequate treatment and 27% among patients who were
      receiving inadequate treatment (P=.131, by E-test). CONCLUSION: Most clinical
      Lactobacillus blood isolates demonstrated low MICs of imipenem, piperacillin
      tazobactam, erythromycin, and clindamycin, but they had variable susceptibility
      to penicillin and cephalosporins.

PMID- 16447102
TI  - Quantitative histological examination of bioprosthetic heart valves.
AB  - BACKGROUND: The histological features that characterize infective endocarditis in
      bioprosthetic valves are not accurately defined. Moreover, bioprosthetic valves
      may have a noninfective, degenerative evolution associated with calcifications,
      vegetation-like lesions, and inflammatory infiltrates. Such histological findings
      may be misdiagnosed as infective endocarditis. METHODS: Pathologic analysis of
      inflamed bioprosthetic valve tissues was conducted retrospectively for 21
      patients who underwent surgical removal of a bioprosthetic valve because of
      suspected infective endocarditis and for 67 patients who underwent surgical
      removal of a bioprosthetic valve because of noninfective dysfunction. To better
      define the histological criteria for infective endocarditis, we used quantitative
      image analysis to compare these 2 groups of patients with respect to vegetations,
      calcifications, and patterns of inflammation. RESULTS: Histologically, infective
      endocarditis in patients with bioprostheses was characterized by demonstration of
      microorganisms, vegetations, and neutrophil-rich, inflammatory infiltrates. Valve
      tissue specimens from patients whose bioprosthetic valves were removed because of
      noninfective complications showed, in 30% of cases, inflammatory infiltrates
      mainly composed of macrophages and lymphocytes. Inflammatory adherent thrombi
      that can occur to the surface of noninfective degenerative bioprostheses are
      differentiated because their vegetations have macrophage-rich content. A
      neutrophil surface area with a cutoff value of > or =1.5% of the total valve
      tissue surface area is highly specific (94%) for infective endocarditis.
      CONCLUSIONS: When no microorganisms are detected and vegetations are not found in
      bioprosthetic valve tissues during the histological examination, a neutrophil
      rich inflammation might better define the term "active endocarditis" in the Duke
      criteria and would allow differentiation between infective endocarditis and
      inflammatory, noninfective valve processes in patients with bioprosthetic valves.

PMID- 16447103
TI  - Efficacy and safety of linezolid compared with vancomycin in a randomized, double
      blind study of febrile neutropenic patients with cancer.
AB  - BACKGROUND: Gram-positive pathogens can cause serious infections in neutropenic
      patients with cancer, and vancomycin therapy is often initiated empirically.
      Linezolid may offer an option for these patients. METHODS: To compare the safety
      and efficacy of linezolid and vancomycin in febrile, neutropenic patients with
      cancer, we conducted a double-blind, multicenter equivalence study. Eligible
      patients with proven or suspected infection due to a gram-positive pathogen were
      randomized to receive linezolid or vancomycin. RESULTS: Clinical success rates 7
      days after completion of therapy (primary end point) were equivalent between
      groups in the intent-to-treat (ITT) analysis (linezolid, 219 [87.3%] of 251
      patients; vancomycin, 202 [85.2%] of 237 patients; 95% CI, -4.1 to 8.1; P=.52),
      modified ITT analysis, clinically evaluable analysis, and microbiologically
      evaluable analysis, as well as between subsets analyzed by malignancy and
      infection type. Mean time to defervescence was shorter for linezolid than
      vancomycin in the modified ITT (6.6 vs. 8.5 days; P=.04) and microbiologically
      evaluable subsets (5.9 vs. 9.1 days; P=.01), although post hoc analyses revealed
      delayed recovery of absolute neutrophil counts for linezolid in these subsets
      (P<.05). There were no between-group differences in microbiologic success rates
      in the modified ITT subset (41 [57.7%] of 71 patients vs. 29 [50.0%] of 58
      patients; P=.38) and microbiologically evaluable subsets, as well as in mortality
      rates in the ITT subset (17 [5.6%] of 304 patients vs. 23 [7.6%] of 301 patients;
      P=.31) and all subsets. Distribution of adverse events, including reported
      hematologic events, was similar between groups, except that linezolid was
      associated with fewer drug-related adverse events (52 [17.2%] of 303 patients vs.
      72 [24.0%] of 300 patients; P=.04) and fewer cases of drug-related renal failure
      (1 [0.3%] of 303 patients vs. 7 [2.3%] of patients; P=.04). CONCLUSIONS:
      Linezolid demonstrated efficacy and similar safety outcomes equivalent to those
      for vancomycin in febrile neutropenic patients with cancer.

PMID- 16447104
TI  - Amphotericin B colloidal dispersion for the treatment of Indian visceral
      leishmaniasis.
AB  - BACKGROUND: In Bihar, India, where visceral leishmaniasis (VL) is hyperendemic
      and refractory to antimony, amphotericin B is the most effective option for the
      treatment of VL. Lipid formulations of amphotericin B are able to circumvent the
      toxic effect of conventional amphotericin B, and the total dose of these
      formulations can be administered over a short duration. However, cost is a major
      constraint in the use of lipid formulations of amphotericin B. Amphotericin B
      colloidal dispersion (ABCD), which is a less expensive lipid formulation, has not
      been tested for the treatment of VL in India. METHODS: In an open-label,
      randomized clinical trial, we evaluated the efficacy and safety of a 6-day course
      of ABCD administered to 3 different dose groups (total dose: 7.5 mg/kg [group A],
      10 mg/kg [group B], and 15 mg/kg [group C]), each of which included a cohort of
      135 patients. RESULTS: Although infusion-related fever and chills occurred in 56%
      68% of patients in the 3 different dose groups, 401 of 405 patients completed the
      treatment. All 135 patients in group A completed treatment, and the final cure
      rate for this group was 97%. In the group that received the highest dose of ABCD
      (group C), severe backache, an unusual side effect, was observed in 8 patients
      (5.92%). Serious adverse effects led to the withdrawal of 2 patients (1.48%) each
      from group B and group C. CONCLUSIONS: Although the cost of ABCD is prohibitive,
      the high level of efficacy associated with short-term treatment with low-dose
      ABCD provides another alternative for the treatment of VL, especially in regions
      where VL is antimony refractory.

PMID- 16447105
TI  - Treatment of plague with gentamicin or doxycycline in a randomized clinical trial
      in Tanzania.
AB  - BACKGROUND: Over the past 50 years, antibiotics of choice for treatment of
      plague, including streptomycin, chloramphenicol, and tetracycline, have mostly
      become outdated or unavailable. To test gentamicin in the treatment of naturally
      occurring plague and the implications of its use in the treatment of bioterrorist
      plague, a randomized, comparative, open-label, clinical trial comparing
      monotherapy with gentamicin or doxycycline was conducted in Tanzania. METHODS:
      Sixty-five adults and children with symptoms of bubonic, septicemic, or pneumonic
      plague of < or =3 days duration were enrolled in the study. Bubo aspirates and
      blood were cultured for Yersinia pestis. Acute-phase and convalescent-phase serum
      samples were tested for antibody against fraction 1 antigen of Y. pestis. Thirty
      five patients were randomized to receive gentamicin (2.5 mg/kg intramuscularly
      every 12 h for 7 days), and 30 patients were randomized to receive doxycycline
      (100 mg [adults] and 2.2 mg/kg [children] orally every 12 h for 7 days). Serum
      creatinine concentrations were measured before and after treatment, and peak and
      trough concentrations of antibiotics were measured. RESULTS: Three patients, 2 of
      whom were treated with gentamicin and 1 of whom was treated with doxycycline,
      died on the first or second day of treatment, and these deaths were attributed to
      advanced disease and complications including pneumonia, septicemia, hemorrhage,
      and renal failure at the start of therapy. All other patients experienced cure or
      an improved condition after receiving therapy, resulting in favorable response
      rates of 94% for gentamicin (95% CI, 81.1%-99.0%) and 97% for doxycycline (95%
      CI, 83.4%-99.8%). Y. pestis isolates obtained from 30 patients belonged to
      biotype antigua and were susceptible to gentamicin and doxycycline, which had
      MICs of 0.13 mg/L and 0.25-0.5 mg/L, respectively. Serum concentrations of
      antibiotics were within therapeutic ranges, and adverse events were infrequent.
      Patients treated with gentamicin demonstrated a modest increase in the mean serum
      creatinine concentration after treatment (P<.05, by paired t test). CONCLUSIONS:
      Both gentamicin and doxycycline were effective therapies for adult and pediatric
      plague, with high rates of favorable responses and low rates of adverse events.

PMID- 16447106
TI  - Real-time polymerase chain reaction assay for the rapid detection and
      characterization of chloroquine-resistant Plasmodium falciparum malaria in
      returned travelers.
AB  - BACKGROUND: Imported drug-resistant malaria is a growing problem in
      industrialized countries. Rapid and accurate diagnosis is essential to prevent
      malaria-associated mortality in returned travelers. However, outside of a limited
      number of specialized centers, the microscopic diagnosis of malaria is slow,
      unreliable, and provides little information about drug resistance. Molecular
      diagnostics have the potential to overcome these limitations. OBJECTIVE: We
      developed and evaluated a rapid, real-time polymerase chain reaction (PCR) assay
      to detect Plasmodium falciparum malaria and chloroquine (CQ)-resistance
      determinants in returned travelers who are febrile. METHODS: A real-time PCR
      assay based on detection of the K76T mutation in PfCRT (K76T) of P. falciparum
      was developed on a LightCycler platform (Roche). The performance characteristics
      of the real-time assay were compared with those of the nested PCR-restriction
      fragment-length polymorphism (RFLP) and the sequence analyses of samples obtained
      from 200 febrile returned travelers, who included 125 infected with P. falciparum
      (48 of whom were infected CQ-susceptible [K76] and 77 of whom were CQ-resistant
      [T76] P. falciparum), 22 infected with Plasmodium vivax, 10 infected with
      Plasmodium ovale, 3 infected with Plasmodium malariae malaria, and 40 infected
      with other febrile syndromes. All patient samples were coded, and all analyses
      were performed blindly. RESULTS: The real-time PCR assay detected multiple pfcrt
      haplotypes associated with CQ resistance in geographically diverse malaria
      isolates acquired by travelers. Compared with nested-PCR RFLP (the reference
      standard), the real-time assay was 100% sensitive and 96.2% specific for
      detection of the P. falciparum K76T mutation. CONCLUSION: This assay is rapid,
      sensitive, and specific for the detection and characterization of CQ-resistant P.
      falciparum malaria in returned travelers. This assay is automated, standardized,
      and suitable for routine use in clinical diagnostic laboratories.

PMID- 16447107
TI  - Active surveillance for acute viral hepatitis in rural villages in the Nile
      Delta.
AB  - BACKGROUND: Acute viral hepatitis is less frequent in Egypt than serum antibody
      levels suggest. Because acute viral hepatitis has a wide clinical spectrum, we
      tested the hypothesis that many cases are undetected because of mild illness
      caused by initial, early-childhood exposure to hepatitis viruses. METHODS: During
      active case detection among 20,000 inhabitants of rural villages in Egypt, we
      screened 1715 symptomatic patients for serum alanine aminotransferase (ALT)
      levels. Viral hepatitis markers were tested in 47 subjects who had ALT levels
      that were least twice the normal level. RESULTS: Of the 47 individuals tested, 4
      children aged 3-5 years had immunoglobulin M (IgM) antibodies to hepatitis A
      virus (anti-HAV IgM). One also had a possible false-positive result to a test for
      IgM antibodies to hepatitis E virus. None had serological evidence of acute
      hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. However,
      33 of the remaining 43 had active HCV infection, having both antibodies to HCV
      (anti-HCV) and HCV RNA. Four others anti-HCV without HCV RNA, and 2 others had
      seroconversion to anti-HCV during follow-up. Two patients who were positive for
      hepatitis B surface antigen had chronic HBV infection. Only 3 with elevated ALT
      levels had no evidence of acute or chronic infections with known hepatitis
      viruses. Immunoglobulin G antibodies to hepatitis E virus was detected in 40
      patients. CONCLUSION: Active surveillance covering approximately 50,000 person
      years detected only 4 cases of acute HAV infection. Almost all persons with mild
      symptoms and elevated ALT levels had serological evidence of chronic viral
      hepatitis, most often associated with HCV. Many of these cases were probably
      "flare-ups" of HCV infection or incidental illness in patients with chronic HCV
      infection, but some could have been caused by difficult-to-confirm initial HCV
      infections. Although serological evidence for exposures was highly prevalent,
      hepatitis viruses seldom caused acute viral hepatitis in these communities.

PMID- 16447108
TI  - Detection of the new human coronavirus HKU1: a report of 6 cases.
AB  - BACKGROUND: Human coronavirus HKU1 (HCoV-HKU1), a new group 2 coronavirus, was
      first characterized in 2005 from 2 adults with pneumonia in Hong Kong, China. To
      the best of our knowledge, there is no other report to date about the detection
      of this new virus. We report a molecular method allowing for the detection of
      HCoV-HKU1 and also report the clinical presentation of 6 infected patients.
      METHODS: We screened 141 specimens (135 nasal samples and 6 stool samples)
      received in February and March 2005 in our laboratory and obtained from 135
      hospitalized patients (61.5% of whom were <5 years old and 34.1% of whom were >20
      years old) for HCoV-HKU1. RESULTS: HCoV-HKU1 was detected in 6 (4.4%) of the 135
      nasal specimens and in 2 (33.3%) of the 6 stool samples; the positive samples
      were obtained from 6 patients (5 children and 1 adult). The clinical presentation
      of these 6 patients was as follows: 3 were admitted to the hospital for acute
      enteric disease resulting in severe dehydration associated with upper respiratory
      symptoms; 1 had fever, otitis, and febrile seizure; 1 had a sample obtained to
      investigate failure to thrive; and 1 had a sample obtained for exploration of X
      linked agammaglobulinemia and hyperleucocytosis. CONCLUSION: HCoV-HKU1 can be
      detected in respiratory and stool samples from children and adults in a part of
      the world other than Hong Kong. Our results suggest that HCoV-HKU1 could be
      associated with respiratory and enteric diseases, and its detection can be
      related to a persistent asymptomatic infection in patients with poor underlying
      conditions.

PMID- 16447109
TI  - The association of respiratory syncytial virus infection and influenza with
      emergency admissions for respiratory disease in London: an analysis of routine
      surveillance data.
AB  - BACKGROUND: The importance of respiratory syncytial virus (RSV) infection in
      adults is not well known, because laboratory testing for RSV infection is not
      routine. Both RSV infection and influenza are seasonally related, and it is
      difficult to disentangle one from the other and to disentangle infection from the
      season and the cold. METHODS: Emergency hospitalizations for respiratory disease
      from April 1994 to March 2001 were analyzed in relation to surveillance data on
      RSV infection and influenza, using Poisson regression models adapted for time
      series and adjusted for season, outdoor temperature, and other covariates. Age
      specific admission rates attributable to the viruses were also estimated.
      RESULTS: Most of the crude relationships of emergency admissions of patients with
      RSV infection were confounded by season and, to a lesser extent, by cold
      temperatures. After adjustment for all covariates, including influenza, a 10th
      90th percentile increase in RSV counts (defined as the daily number of laboratory
      reports of RSV) was associated with a rate ratio of 1.36 (95% CI, 1.27-1.45) for
      emergency admissions for respiratory disease in infants. The rate of
      hospitalization attributable to RSV infection in children aged <1 year was 5 per
      1000 infants per year. The association in people > or =65 years old was much
      smaller (rate ratio, 1.09; 95% CI, 1.04-1.14; attributable rate of
      hospitalization , 0.7 per 1000 population); but unlike the association in
      infants, this association became smaller as the lag (interval) between infection
      and hospital admission became shorter. Admission rates attributable to influenza
      were highest in the > or =65-year age group (1.1 per 1000 population), but it was
      very small at younger ages. CONCLUSIONS: RSV infection appears to be an important
      determinant of hospitalization in infants in this data set but appears less
      certain for older persons and requires further investigation.

PMID- 16447110
TI  - Emergence of community-associated methicillin-resistant Staphylococcus aureus
      USA300 genotype as a major cause of health care-associated blood stream
      infections.
AB  - BACKGROUND: Whether community-associated methicillin-resistant Staphylococcus
      aureus (MRSA) genotypes (e.g., USA300) are a major cause of bloodstream
      infections (BSIs) and health care-associated infections has been poorly defined.
      METHODS: Consecutive MRSA isolates recovered from patients with BSIs were
      prospectively collected at an urban public hospital. Molecular typing studies
      were performed. Prevalence and risk factors for the MRSA USA300 genotype were
      assessed. RESULTS: One hundred thirty-two cases of MRSA BSI were documented over
      7.5 months in 2004 (incidence, 6.79 per 1000 admissions); 116 isolates were
      available for genotyping. Characteristics of the 116 evaluable cases included: a
      mean age 47 years; 62% were male, 82% were African American, and 22% were HIV
      seropositive. The crude in-hospital mortality rate was 22%. In 107 cases (92%),
      there was contact with a health care facility within the year prior to infection,
      and a nosocomial infection (defined as positive blood culture results obtained
      >48 h after admission) occurred in 49 cases (42%). PFGE demonstrated that 39
      (34%) of the 116 isolates were the MRSA USA300 genotype; 34 (29%) were USA100; 42
      (36%) were USA500; and 1 (1%) was USA800. MRSA USA300 accounted for 28% of health
      care-associated BSIs and 20% of nosocomial MRSA BSIs. In multivariate analysis,
      isolation of the USA300 genotype was associated with injectiondrug use (OR, 3.67;
      95% CI, 1.10-12.28) and skin and soft tissue infection (OR, 4.26; 95% CI, 1.08
      16.84). Patients who resided in long-term care facilities (OR, 0.09; 95% CI, 0.01
      0.82) and those who were treated with antimicrobials in the prior year were less
      likely to have MRSA USA300 genotype recovered (OR, 0.10; 95% CI, 0.02-0.49).
      CONCLUSIONS: MRSA USA300 genotype, the predominant cause of community-associated
      MRSA infections in our area (Atlanta, GA), has now emerged as a significant cause
      of health care-associated and nosocomial BSI. MRSA USA300 as a nosocomial
      pathogen presents new challenges to infection control programs.

PMID- 16447111
TI  - Bad bugs need drugs: an update on the development pipeline from the Antimicrobial
      Availability Task Force of the Infectious Diseases Society of America.
AB  - The Antimicrobial Availability Task Force (AATF) of the Infectious Diseases
      Society of America (IDSA) has viewed with concern the decreasing investment by
      major pharmaceutical companies in antimicrobial research and development.
      Although smaller companies are stepping forward to address this gap, their
      success is uncertain. The IDSA proposed legislative and other federal solutions
      to this emerging public health problem in its July 2004 policy report "Bad Bugs,
      No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews." At this
      time, the legislative response cannot be predicted. To emphasize further the
      urgency of the problem for the benefit of legislators and policy makers and to
      capture the ongoing frustration our clinician colleagues experience in their
      frequent return to an inadequate medicine cabinet, the AATF has prepared this
      review to highlight pathogens that are frequently resistant to licensed
      antimicrobials and for which few, if any, potentially effective drugs are
      identifiable in the late-stage development pipeline.

PMID- 16447112
TI  - Eligibility for treatment of hepatitis C virus infection among young injection
      drug users in 3 US cities.
AB  - Among 404 injection drug users aged 18-35 who tested positive for hepatitis C
      virus (HCV) RNA, 96% had conditions that are potentially unwarranted
      contraindications for HCV treatment (e.g., problem drinking, moderate-to-severe
      depression, and recent drug injection). Restrictive eligibility criteria may deny
      treatment to a large proportion of patients who could benefit from it.

PMID- 16447114
TI  - Climate change and the end of the respiratory syncytial virus season.
AB  - The seasons associated with laboratory isolation of respiratory syncytial virus
      (RSV) (for 1981-2004) and RSV-related emergency department admissions (for 1990
      2004) ended 3.1 and 2.5 weeks earlier, respectively, per 1 degrees C increase in
      annual central England temperature (P=.002 and .043, respectively). Climate
      change may be shortening the RSV season.

PMID- 16447113
TI  - Injection drug users: the overlooked core of the hepatitis C epidemic.

PMID- 16447115
TI  - Persistent neuroinvasive West Nile virus infection in an immunocompromised
      patient.
AB  - A 57-year-old man who had received treatment for B cell lymphoma presented with
      West Nile virus (WNV) meningoencephalitis. During his 99-day hospitalization, no
      WNV-specific antibodies were detected. In postmortem central nervous system
      samples obtained at autopsy, WNV RNA and WNV antigens were detected. This
      patient's case raises important issues related to the diagnosis, pathogenesis,
      and possible treatment of persistent WNV infection.

PMID- 16447116
TI  - Human health implications of Salmonella-contaminated natural pet treats and raw
      pet food.
AB  - Human salmonellosis occurs mainly as a result of handling or consuming
      contaminated food products, with a small percentage of cases being related to
      other, less well-defined exposures, such as contact with companion animals and
      natural pet treats. The increasing popularity of raw food diets for companion
      animals is another potential pet-associated source of Salmonella organisms;
      however, no confirmed cases of human salmonellosis have been associated with
      these diets. Pets that consume contaminated pet treats and raw food diets can be
      colonized with Salmonella organisms without exhibiting clinical signs, making
      them a possible hidden source of contamination in the household. Pet owners can
      reduce their risk of acquiring Salmonella organisms by not feeding natural pet
      treats and raw food diets to their pets, whereas individuals who investigate
      cases of salmonellosis or interpret surveillance data should be aware of these
      possible sources of Salmonella organisms.

PMID- 16447117
TI  - The epidemiology and control of Acinetobacter baumannii in health care
      facilities.
AB  - Acinetobacter baumannii is a ubiquitous pathogen capable of causing both
      community and health care-associated infections (HAIs), although HAIs are the
      most common form. This organism has emerged recently as a major cause of HAI
      because of the extent of its antimicrobial resistance and its propensity to cause
      large, often multifacility, nosocomial outbreaks. The occurrence of outbreak is
      facilitated by both tolerance to desiccation and multidrug resistance,
      contributing to the maintenance of these organisms in the hospital environment.
      In addition, the epidemiology of A. baumannii infection is often complex, with
      the coexistence of epidemic and endemic infections, the latter of which often is
      favored by the selection pressure of antimicrobials. The only good news is that
      potentially severe A. baumannii infection, such as bacteremia or pneumonia in
      patients in the intensive care unit who are undergoing intubation, do not seem to
      be associated with a higher attributable mortality rate or an increased length of
      hospital stay.

PMID- 16447118
TI  - Seroreversion in subjects receiving antiretroviral therapy during acute/early HIV
      infection.
AB  - BACKGROUND: We assessed human immunodeficiency virus (HIV) antibody seroreversion
      among individuals initiating antiretroviral therapy (ART) during acute/early HIV
      infection and determined whether seroreversion was associated with loss of
      cytotoxic T lymphocyte responses. METHODS: Subjects in a cohort with acute/early
      HIV infection (<12 months into infection) who initiated ART within 28 days after
      study entry and maintained HIV type 1 ribonucleic acid levels of < or =500
      copies/mL for >24 weeks were selected. Two clinically available second-generation
      enzyme immunoassays (EIAs) and a confirmatory Western blot were used to screen
      subjects for antibody reversion. Those with negative screening test results
      underwent additional antibody testing, including a third-generation EIA, and were
      assessed for cytotoxic T lymphocyte responses. RESULTS: Of 87 subjects
      identified, 12 (14%) had negative antibody test results at the start of ART; all
      12 had seroconversion, although 1 had seroconversion only on a third-generation
      EIA. Of the 87 subjects, 6 (7%) had seroreversion on at least 1 EIA antibody
      assay while receiving ART during a median follow-up of 90 weeks. The only
      clinical predictor of seroreversion was a low baseline "detuned" (less sensitive)
      antibody. Cytotoxic T lymphocyte responses to HIV Gag peptides were detected in 4
      of 5 subjects with seroreversion who could be tested. All 5 who had seroreversion
      who stopped ART experienced virologic rebound and antibody evolution.
      CONCLUSIONS: HIV antibody seroconversion on second-generation EIA antibody tests
      may fail to occur when ART is initiated early. Seroreversion was not uncommon
      among subjects treated early, although cytotoxic T lymphocyte responses to HIV
      antigens remained detectable in most subjects. Antibody seroreversion did not
      indicate viral eradication. A third-generation EIA was the most sensitive test
      for HIV antibodies.

PMID- 16447119
TI  - CD4 cell count and HIV DNA level are independent predictors of disease
      progression after primary HIV type 1 infection in untreated patients.
AB  - BACKGROUND: Treatment initiation at the time of primary human immunodeficiency
      virus (HIV) type 1 (HIV-1) infection has become less frequent in recent years.
      METHODS: In the French prospective PRIMO Cohort, in which patients are enrolled
      at the time of primary HIV-1 infection, 30% of the 552 patients recruited during
      1996-2004 did not start receiving antiretroviral treatment during the first 3
      months after diagnosis. We analyzed the patients' clinical and immunological
      outcomes and examined potential predictors of disease progression. Progression
      was defined as the occurrence of an acquired immunodeficiency syndrome (AIDS)
      related clinical event or a CD4 cell count <350 cells/mm3. RESULTS: Fifty-six
      (34%) of the untreated patients experienced immunological progression during a
      median duration of follow-up of 24 months, and 1 of these patients had an AIDS
      related event. The estimated risks of progression were 25%, 34%, and 42% at 1, 2,
      and 3 years after enrollment, respectively. Compared with patients who did not
      have progression, those with progression had significantly lower CD4 cell counts
      at diagnosis (455 vs. 738 cells/mm3), higher plasma HIV RNA levels (4.9 vs. 4.5
      log10 copies/mL), and higher HIV DNA levels (3.3 vs. 3.0 log(10) copies/10(6)
      peripheral blood mononuclear cells [PBMCs]). All 3 parameters were significantly
      associated with progression in univariate analysis. In multivariate analysis,
      only the CD4 cell count and HIV DNA level were independently predictive of
      disease progression (relative hazard for CD4 cell count, 1.84 per decrease of 100
      cells/mm3; relative hazard for HIV DNA level, 2.73 per increase of 1 log(10)
      copies/10(6) PBMCs). CONCLUSIONS: Both a low initial CD4 cell count and a high
      HIV DNA level are predictive of rapid progression of untreated primary HIV-1
      infection. Affected patients may therefore benefit from close clinical and
      laboratory monitoring and/or early administration of treatment.

PMID- 16447121
TI  - Poor infection control, not fluoroquinolones, likely to be primary cause of
      Clostridium difficile-associated diarrhea outbreaks in Quebec.

PMID- 16447120
TI  - Models for integrating buprenorphine therapy into the primary HIV care setting.
AB  - Opiate dependence among human immunodeficiency virus (HIV)-infected patients has
      been associated with negative clinical outcomes, yet few affected patients
      receive appropriate and coordinated treatment for both conditions. The
      introduction of buprenorphine maintenance therapy into HIV care settings provides
      an opportunity for providers to integrate treatment for opiate dependence into
      their practices. Buprenorphine maintenance therapy has been associated with
      reductions in opiate use, increased social stability, improved adherence to
      antiretroviral therapy, and lowered rates of injection drug use. We describe the
      following 4 models for the integration of buprenorphine maintenance therapy into
      HIV care: (1) a primary care model, in which the highly active antiretroviral
      therapy-administering clinician also prescribes buprenorphine; (2) a model that
      relies on an on-site specialist in addiction medicine or psychiatry to prescribe
      the buprenorphine; (3) a hybrid model, in which an on-site specialist provides
      the induction (with or without stabilization phases) and the HIV care provider
      provides the maintenance phase; and (4) a drug treatment model that provides
      buprenorphine maintenance therapy services with HIV services in the substance
      abuse clinic setting. The key barriers against effective integration of
      buprenorphine maintenance therapy and primary HIV services are discussed, and we
      suggest several mechanisms to overcome such obstacles.

PMID- 16447122
TI  - Clostridium difficile-associated diarrhea outbreaks: the name of the game is
      isolation and cleaning.

PMID- 16447124
TI  - Successful treatment of staphylococcal toxic shock syndrome with linezolid: a
      case report and in vitro evaluation of the production of toxic shock syndrome
      toxin type 1 in the presence of antibiotics.

PMID- 16447126
TI  - Spanish royal philanthropic expedition and smallpox vaccination.

PMID- 16447127
TI  - An unjustifiably alarming report of a fatal case of retroviral rebound syndrome.

PMID- 16447129
TI  - Cytomegalovirus ileitis and hemophagocytic syndrome associated with use of anti
      tumor necrosis factor-alpha antibody.

PMID- 16447130
TI  - Vaccine supply problems: a perspective of the Centers for Disease Control and
      Prevention.
AB  - Although immunization is one of the great public health achievements, continued
      success depends on an available supply of the vaccines that are recommended for
      routine use. Beginning in 2000, the United States experienced vaccine supply
      disruptions of unprecedented scope and magnitude. Although most of the supply
      disruptions have been resolved, it appears that a fragile vaccine supply will be
      part of the immunization environment in the United States for the foreseeable
      future. Here, we describe the perspective of the Centers for Disease Control and
      Prevention on the recent supply disruptions and the methods used to manage
      vaccine shortages. The present article focuses on routine pediatric vaccines,
      including influenza virus vaccine.

PMID- 16447131
TI  - Keys to strengthening the supply of routinely recommended vaccines: view from
      industry.
AB  - The vaccine enterprise in the United States is a remarkable success story that
      has resulted in freedom from disease for millions of children. Although some
      persons believe that this success is in danger because of recent vaccine
      shortages, the reality is otherwise. The existing system fundamentally works and
      should be strengthened and stabilized, to improve delivery of current vaccines
      and to establish a firm structure into which a new generation of vaccines can be
      integrated. Ten practical actions to strengthen supplies of vaccine and ensure
      the stability of these supplies were presented to the National Vaccine Advisory
      Committee in February 2002. The present article has been updated to include
      progress made since that time. By building on what is already in place and on
      what we know works, we can continue to ensure success for years to come.

PMID- 16447132
TI  - Establishing government-operated vaccine programs: an industry perspective.
AB  - During 2000-2002, shortages of numerous routinely administered pediatric vaccines
      occurred. The reasons for these shortages were varied, but they included policy,
      manufacturing, and regulatory issues. The use of government manufacturing
      programs has been proposed as a way to stabilize the fragile vaccine supply and
      to prevent periodic shortages. Although such programs might be useful for defense
      needs, it is likely that such an approach would have limited value for routinely
      administered vaccines. Each of the vaccine components would require a dedicated
      manufacturing facility, and many components are administered in combination
      vaccines. Timing is also an important consideration. The restarting of an idled
      manufacturing facility would take many months; in addition, it often takes nearly
      12 months to produce and release a single lot of vaccine. Finally, government
      owned programs would face the same issues of regulatory changes, technological
      advancements, and facility updates as non-government-owned programs do--all of
      which would require sustained operation and investment. A secure and stable
      vaccine supply is best built by establishing the importance and value of our
      vaccine programs, which would, in turn, provide incentives to manufacturers to
      build capacity and inventories.

PMID- 16447133
TI  - Strengthening the supply of routinely recommended vaccines in the United States:
      a perspective from the American Medical Association.
AB  - Influenza virus vaccine shortages and delays in distribution require continued
      collaborative efforts by all stakeholders to ensure that Healthy People 2010
      goals are met. Problems with supplies of other vaccines jeopardize at-risk
      populations. The American Medical Association recommends that the US Department
      of Health and Human Services establish a task force to explore the causes of
      vaccine shortages and maldistribution. The task force should commission an
      appropriate body of experts to identify solutions for breakdowns in vaccine
      manufacturing and distribution systems. Potential areas for improvement include
      earlier notification of shortages to the US Food and Drug Administration,
      improved communication to physicians, financial incentives to market medically
      necessary but unprofitable products, and a national stockpile of certain
      vaccines. The American Medical Association believes that the strategies proposed
      by the National Vaccine Program Office (i.e., increasing financial incentives,
      streamlining the regulatory process, establishing government-directed programs,
      creating and maintaining vaccine stockpiles, and increasing liability protection)
      could improve vaccine availability; however, increasing vaccine stockpiles is the
      most promising strategy.

PMID- 16447134
TI  - The United States pediatric vaccine stockpile program.
AB  - The initial goal of the national vaccine stockpile program was to establish a 6
      month supply of all recommended childhood vaccines, to meet national demands if a
      manufacturing process was interrupted. When the first vaccine stockpiles were
      created in 1983, the childhood immunization schedule was much less complicated
      than it is today, and the first stockpiles included only measles-mumps-rubella,
      poliovirus, and pertussis vaccines, as well as diphtheria and tetanus toxoids.
      However, today's vaccine needs are much greater, and current stockpiles do not
      include all recommended childhood vaccines, partially because inclusion of
      vaccines that are universally recommended, fully implemented, and produced by a
      single manufacturer has been made a priority. Future planning must also consider
      substantially higher vaccine costs, the development of new combination vaccines,
      a wide range of production times, and changes in immunization recommendations.
      Expansion and strengthening of the national vaccine stockpile program are
      critical to protect against future disruptions in vaccine supply.

PMID- 16447135
TI  - Update on vaccine liability in the United States: presentation at the National
      Vaccine Program Office Workshop on strengthening the supply of routinely
      recommended vaccines in the United States, 12 February 2002.
AB  - Two decades ago, a liability crisis brought on by concerns about the safety of
      diphtheria and tetanus toxoids and pertussis vaccine led to supply shortages and
      calls for rationing of the vaccine. Vaccine prices skyrocketed, and research on
      new products was threatened. In response, Congress created the National Vaccine
      Injury Compensation Program, which is tort reform legislation designed to
      compensate individuals quickly, easily, and generously. Since 1988, the Vaccine
      Injury Compensation Program has stabilized the marketplace, as evidenced by high
      immunization rates, stable pricing, and an increasing number of vaccine
      candidates in development. Although current vaccine shortages do not appear to be
      related to issues of liability, a new wave of tort litigation alleging that some
      vaccines cause autism has led to speculation that history could repeat itself.

PMID- 16447136
TI  - Tailoring the strategies to specific shortages: pneumococcal conjugate vaccine.
AB  - Less than 1 year after recommendations for the routine vaccination of infants
      with the newly licensed 7-valent polysaccharide-protein conjugate pneumococcal
      vaccine were issued in February 2000, shortages of the 7-valent polysaccharide
      protein conjugate pneumococcal vaccine supply began to occur. A national shortage
      developed in 2001, involving both the public and private sectors, and it resulted
      in temporary recommendations to conserve vaccine supply for infants and young
      children at the highest risk for invasive disease. Multiple factors contributed
      to this vaccine shortage, including demand that exceeded the expectations of the
      manufacturer and the need for compliance with the Good Manufacturing Practice of
      the US Food and Drug Administration. Of the possible strategies that might have
      averted this shortage, establishment of a vaccine stockpile is the most likely
      solution. However, establishing a stockpile for a newly licensed vaccine, such as
      7-valent polysaccharide-protein conjugate pneumococcal vaccine, presents unique
      challenges. Improved communication with physicians and parents regarding changes
      in vaccine schedules also will promote better adherence to recommended changes
      and conservation of limited vaccine supplies during a shortage.

PMID- 16447137
TI  - A response to strategy #2: streamlining the regulatory process.
AB  - Regulatory burden has contributed to the decline in the production of vaccines in
      the United States. Production of influenza virus vaccine is perilously limited at
      a critical period when vulnerable populations are increasing and the threat of a
      pandemic is looming. Regulatory bodies must work with manufacturers to facilitate
      implementation of new production practices, to ensure steady expansion of the
      supply of safe and effective vaccines.

PMID- 16447138
TI  - Strengthening the supply of routinely administered vaccines in the United States:
      progress and problems--2005.

PMID- 16447139
TI  - Strengthening the supply of routinely administered vaccines in the United States:
      problems and proposed solutions.
AB  - At the request of the Assistant Secretary for Health of the United States
      Department of Health and Human Services, the National Vaccine Advisory Committee
      organized workshops in February 2002 and January 2005 to identify the reasons for
      vaccine shortages and to develop strategies to prevent shortages in the future.
      This supplement to Clinical Infectious Diseases includes presentations outlining
      the problems associated with and proposed solutions for strengthening the supply
      of routinely administered vaccines in the United States.

PMID- 16447140
TI  - A pilot study investigating a novel subcutaneously implanted pre-cellularised
      scaffold for tissue engineering of intestinal mucosa.
AB  - Tissue engineering of the small intestine offers an alternative to long-term
      intravenous nutrition and transplantation in patients with intestinal failure.
      Initial work, although encouraging, is limited by the volume of neonatal tissue
      required to produce a small neomucosal cyst. Our novel approach is to implant
      tubular poly-lactide-co-glycolide (PGLA) foam scaffolds subcutaneously. The aim
      of this study was to investigate whether these scaffolds would support growth of
      intestinal neomucosa. PGLA scaffolds were implanted subcutaneously into 8 Lewis
      rats; after 5 weeks, 'organoid units' were injected into the lumens. Tissue was
      assessed histologically after harvesting and quantitative immunohistochemistry
      was performed using antibodies against vascular endothelial growth factor (VEGF),
      vascular endothelial growth factor receptor 2 (VEGF-R2), fibroblast growth factor
      basic (bFGF) and fibroblast growth factor receptor 2 (FGF-R2). At 4 weeks post
      organoid unit implantation, clearly recognisable mucosa and submucosa was present
      on the luminal surface of the scaffold. Densities of VEGF and VEGF-R2 positive
      cells increased with time post organoid unit implantation. This pilot study
      demonstrates that it is possible to tissue engineer small intestinal neomucosa
      using subcutaneously implanted PLGA scaffolds. The yield of the process compares
      favourably to the published literature. Further work is required to optimise the
      technique.

PMID- 16447141
TI  - Captopril protects mice bone marrow cells against genotoxicity induced by gamma
      irradiation.
AB  - The radioprotective effects of captopril were investigated by using the
      micronucleus test for anticlastogenic and cell proliferation activity. A single
      intraperitoneal administration of captopril at doses of 10, 25 and 50 mg/kg 1 h
      prior to gamma irradiation (2 Gy) reduced the frequencies of micronuleated
      polychromatic erythrocytes (MnPCEs). All three doses of captopril significantly
      reduced the frequencies of MnPCEs and increased polychromatic erythrocytes
      (PCE)/PCE+NCE (normochromatic erythrocyte) ratio in mice bone marrow compared to
      the non-drug-treated irradiated control (p < 0.001). The optimum dose for
      protection in mouse was 10 mg/kg to protect mice bone marrow 2.18-fold against
      the clastogenic effects of gamma-irradiation with respect to the non-drug-treated
      irradiated control. There was a drug dose-response effect of captopril in
      increasing the PCE/PCE+NCE ratio in bone marrow cells. The maximum protective
      effect of captopril was at a dose of 25 mg/kg for increasing the PCE/PCE + NCE
      ratio. Captopril exhibited concentration-dependent antioxidant activity,
      scavenging > 96% of the 1,1-diphenyl-2-picryl hydrazyl free radicals when used at
      a concentration of 0.2 mM. In this study captopril reduced lipid peroxidation
      induced by hydrogen peroxide in mice liver. It appears that captopril, due to its
      free radical scavenging properties, protects mice bone marrow cells from
      radiation-induced DNA damage and genotoxicity.

PMID- 16447142
TI  - Surface-activated chemical ionization versus electrospray ionization in the study
      of selected aluminium(III)/ligand solution equilibria.

PMID- 16447143
TI  - Lipid peroxidation and total antioxidant status in patients with breast cancer.
AB  - Oxidative stress is considered to be involved in the pathophysiology of all
      cancers. The aim of this study is to examine oxidative stress and antioxidant
      status in patients with breast cancer by evaluation of the serum levels of total
      antioxidant capacity (TAC) and lipid peroxidation products as malondialdehyde
      (MDA) and lipid hydroperoxide and to investigate the relationship between these
      parameters, oxidative stress and serum lipids and lipoproteins. In our study,
      serum TAC, MDA, lipid hydroperoxide, HDL-cholesterol, VLDL-cholesterol, LDL
      cholesterol, total cholesterol, triacylglycerol (TAG), albumin and uric acid
      levels of 56-breast cancer patients in different clinical stages and 18 healthy
      women were determined. Significantly lower-levels of TAC were detected in
      patients with breast cancer in comparison to controls (2.01 +/- 0.01 mmol/l and
      2.07 +/- 0.03 mmol/l, respectively, p < 0.05). Serum MDA levels of the patients
      were higher compared to the controls (3.64 +/- 0.25 microM and 2.72 +/- 0.22
      microM, respectively, p < 0.05). No significant difference between lipid
      hydroperoxide levels of patients and controls was found (0.33 +/- 0.05 microM and
      0.32 +/- 0.01 microM, respectively, p > 0.05). These data show that lower TAC and
      higher MDA levels i.e. increased oxidative stress may be related to breast
      cancer.

PMID- 16447144
TI  - Structural analysis of secondary ions by post-source decay in time-of-flight
      secondary ion mass spectrometry.
AB  - Tandem mass spectrometry measurements have been achieved using time-of-flight
      secondary ion mass spectrometry (TOF-SIMS) and a post source decay (PSD)-like
      method. The performance of the method has been demonstrated on model molecules
      with well-known fragmentation pathways. Several lipids have been fragmented
      including the phosphocholine ion, phosphatidylcholines, cholesterol and vitamin
      E. Pure samples were analyzed, and the results compared with those obtained with
      the same compounds on a quadrupole-TOF hybrid mass spectrometer. Then, the
      structures of some lipids which are currently observed in the TOF-SIMS imaging of
      mammalian tissue sections were verified.

PMID- 16447145
TI  - Fast gas chromatography/mass spectrometric assay for the validated quantitative
      determination of methadone and the primary metabolite EDDP in whole blood.
AB  - A toxicological analysis was developed and validated for simultaneous screening
      and quantification of methadone (METH) and its primary metabolite 2-ethylidene
      1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). The method employs microscale liquid
      liquid extraction (microLLE) and direct injection of a separated aliquot of the
      organic layer into a gas chromatography/mass spectrometric (GC/MS) system without
      any other pre-treatment stages. A fast GC/MS runtime (total 5.8 min; METH, Rt =
      3.55 min; EDDP, Rt = 3.40 min) combined with rapid sample preparation allowed
      cost-efficient and routinely applicable performance with a low amount of manual
      work. The validated parameters included: linearity (25-1000 ng mL(-1) both;
      R(METH)2 = 0.998 and R(EDDP)2 = 0.997), accuracy (Bias(METH): from -0.05 to
      11.3%, Bias(EDDP): from 1.11 to 4.37%); intra and inter-assay precision
      (RSD(METH): from 2.4 to 3.9%, from 4.89 to 10.3%; RSD(EDDP): from 4.50 to 6.20%,
      from 4.57 to 15.2%), extraction efficiency (METH = 95.5%; EDDP = 90.6%),
      LOQ(Meth,EDDP) = 25 ng mL(-1). Samples were stable for at least 25 h and no
      selectivity problems or baseline interference were observed. The method should be
      applicable for identifying and quantitative confirmation of possible misuse
      and/or illegal use of METH in toxicological cases.

PMID- 16447146
TI  - The use of desorption/ionization on porous silicon mass spectrometry for the
      detection of negative ions for fatty acids.
AB  - The study of low molecular weight compounds by matrix-assisted laser
      desorption/ionization (MALDI) is difficult because of the presence of ions
      originating from the matrix in the low-m/z range. In order to resolve these
      problems, new matrix-free approaches were developed based on laser
      desorption/ionization from the surface of various materials such as graphite and
      porous silicon. Our work involves the use of 'desorption ionization on porous
      silicon mass spectrometry' (DIOS-MS) in the negative ion mode to study fatty acid
      compounds. The potential of the DIOS-MS technique is shown and an insight into
      the ionization mechanism provided.

PMID- 16447148
TI  - Investigation of vancomycin and related substances by liquid chromatography/ion
      trap mass spectrometry.
AB  - Liquid chromatography (LC) methods compatible with mass spectrometry (MS) that
      are suitable for impurity profiling of vancomycin mixtures have not been
      described in the literature. The mobile phases of the existing methods contain
      non-volatile additives and/or solvents that give problems in combination with MS.
      In this paper, a reversed-phase LC/tandem mass spectrometry method is described
      for the investigation of vancomycin and related substances. The LC method uses a
      Zorbax Extend C18 column (250 x 4.6 mm i.d.), 5 microm, and a mobile phase
      consisting of methanol, water and ammonium acetate solution (pH 9.0). This method
      allows us to separate vancomycin and its impurities. Mass spectral data are
      acquired on an LCQ ion trap mass spectrometer equipped with an electrospray
      interface operated in the positive and negative ion modes. The LCQ is ideally
      suited for identification of impurities and related substances because it
      provides on-line LC/MSn capability, which allows efficient identification without
      time-consuming isolation and purification procedures. Using this method, the
      fragmentation of vancomycin and known derivatives was studied and the structures
      of six substances occurring in commercial samples were elucidated.

PMID- 16447150
TI  - A biomimetic chromanol cyclization leading to alpha-tocopherol.

PMID- 16447152
TI  - Synthesis of naturally occurring polyynes.
AB  - Over the past fifty years, hundreds of polyyne compounds have been isolated from
      nature. These often unstable molecules are found in sources as common as garden
      vegetables and as obscure as bacterial cultures. Naturally occurring polyynes
      feature a wide range of structural diversity and display an equally broad array
      of biological properties. Early synthetic efforts relied primarily on Cu
      catalyzed, oxidative acetylenic homo- and heterocoupling reactions to assemble
      the polyyne framework. The past 25 years, however, have witnessed a renaissance
      in the field of polyyne natural product synthesis: transition-metal-catalyzed
      alkynylation reactions and asymmetric transformations have combined to
      substantially expand access to natural polyynes. This Review recounts these
      synthetic achievements and also highlights both the natural source(s) and
      biological relevance for many of these compounds.

PMID- 16447153
TI  - Down-regulation of the strawberry Bet v 1-homologous allergen in concert with the
      flavonoid biosynthesis pathway in colorless strawberry mutant.
AB  - Proteomic screening of strawberry (Fragaria ananassa) yielded a 58% success rate
      in protein identification in spite of the fact that no genomic sequence is
      available for this species. This was achieved by a combination of MALDI-MS/MS de
      novo sequencing of double-derivatized peptides and indel-tolerant searching
      against local protein databases built on both EST and full-length nucleotide
      sequences. The amino acid sequence of a strawberry allergen, homologous to the
      well-known major birch pollen allergen Bet v 1, was partially determined. This
      strawberry allergen, named Fra a 1 according to the nomenclature for allergen
      proteins, showed sequence identity of 54 and 77%, respectively, with
      corresponding allergens from birch and apple. Differential expression, as
      evaluated by 2-D DIGE, occurred in 10% of protein spots when red strawberries
      were compared to a colorless (white) strawberry mutant. White strawberries, known
      to be tolerated by individuals affected by allergy, were found to be virtually
      free from the strawberry allergen. Also several enzymes in the pathway for
      biosynthesis of flavonoids, to which the red color pelargonidin belongs, were
      down-regulated. This approach to assess differential protein expression without
      access to genomic sequence information can also be applied to other crop plants
      and phenotypic traits.

PMID- 16447154
TI  - Reconstruction of central carbon metabolism in Sulfolobus solfataricus using a
      two-dimensional gel electrophoresis map, stable isotope labelling and DNA
      microarray analysis.
AB  - In the last decade, an increasing number of sequenced archaeal genomes have
      become available, opening up the possibility for functional genomic analyses.
      Here, we reconstructed the central carbon metabolism in the hyperthermophilic
      crenarchaeon Sulfolobus solfataricus (glycolysis, gluconeogenesis and
      tricarboxylic acid cycle) on the basis of genomic, proteomic, transcriptomic and
      biochemical data. A 2-DE reference map of S. solfataricus grown on glucose,
      consisting of 325 unique ORFs in 255 protein spots, was created to facilitate
      this study. The map was then used for a differential expression study based on
      (15)N metabolic labelling (yeast extract + tryptone-grown cells (YT) vs. glucose
      grown cells (G)). In addition, the expression ratio of the genes involved in
      carbon metabolism was studied using DNA microarrays. Surprisingly, only 3 and 14%
      of the genes and proteins, respectively, involved in central carbon metabolism
      showed a greater than two-fold change in expression level. All results are
      discussed in the light of the current understanding of central carbon metabolism
      in S. solfataricus and will help to obtain a system-wide understanding of this
      organism.

PMID- 16447155
TI  - Nanotechnologies in proteomics.
AB  - Progress in proteomic researches is largely determined by development and
      implementation of new methods for the revelation and identification of proteins
      in biological material in a wide concentration range (from 10(-3) M to single
      molecules). The most perspective approaches to address this problem involve (i)
      nanotechnological physicochemical procedures for the separation of multicomponent
      protein mixtures; among these of particular interest are biospecific
      nanotechnological procedures for selection of proteins from multicomponent
      protein mixtures with their subsequent concentration on solid support; (ii)
      identification and counting of single molecules by use of molecular detectors.
      The prototypes of biospecific nanotechnological procedures, based on the capture
      of ligand biomolecules by biomolecules of immobilized ligate and the
      concentration of the captured ligands on appropriate surfaces, are well known;
      these are affinity chromatography, magnetic biobeads technology, different
      biosensor methods, etc. Here, we review the most promising nanotechnological
      approaches for selection of proteins and kinetic characterization of their
      complexes based on these biospecific methods with subsequent MS/MS identification
      of proteins and protein complexes. Two major groups of methods for the analysis
      and identification of individual molecules and their complexes by use of
      molecular detectors will be reviewed: scanning probe microscopy (SPM) (including
      atomic-force microscopy) and cryomassdetector technology.

PMID- 16447156
TI  - Intermittent administration of morphine alters protein expression in rat nucleus
      accumbens.
AB  - Repeated exposure to drugs of abuse causes time-dependent neuroadaptive changes
      in the mesocorticolimbic system of the brain that are considered to underlie the
      expression of major behavioral characteristics of drug addiction. We used a 2-D
      gel-based proteomics approach to examine morphine-induced temporal changes in
      protein expression and/or PTM in the nucleus accumbens (NAc) of morphine
      sensitized rats. Rats were pretreated with saline [1 mL/kg subcutaneously (s.c.)]
      or morphine (10 mg/kg, s.c.) once daily for 14 days and the animals were
      decapitated 1 day later. The NAc was extracted and proteins resolved by 2-DE.
      Several protein functional groups were found to be regulated in the morphine
      treated group, representing cytoskeletal proteins, proteins involved in
      neurotransmission, enzymes involved in energy metabolism and protein degradation,
      and a protein that regulates translation.

PMID- 16447157
TI  - SELDI-TOF MS of quadruplicate urine and serum samples to evaluate changes related
      to storage conditions.
AB  - Proteomic profiling with SELDI-TOF MS has facilitated the discovery of disease
      specific protein profiles. However, multicenter studies are often hindered by the
      logistics required for prompt deep-freezing of samples in liquid nitrogen or dry
      ice within the clinic setting prior to shipping. We report high concordance
      between MS profiles within sets of quadruplicate split urine and serum samples
      deep-frozen at 0, 2, 6, and 24 h after sample collection. Gage R&R results
      confirm that deep-freezing times are not a statistically significant source of
      SELDI-TOF MS variability for either blood or urine.

PMID- 16447158
TI  - Differential protein expression in brain capillary endothelial cells induced by
      hypoxia and posthypoxic reoxygenation.
AB  - Cerebral ischemia causes functional alteration of the blood-brain barrier, formed
      by brain capillary endothelial cells (BCEC). Changes in protein expression and
      activity of selected differentially expressed enzymes were investigated in BCEC
      subjected to hypoxia (24 h) alone or followed by a 24-h reoxygenation. BCEC
      proteins were isolated, separated by 2-DE, and identified by MALDI-MS. Computer
      based 2-D gel analysis identified 21 up-regulated proteins and 4 down-regulated
      proteins after hypoxia alone and 9 proteins that were further up-regulated after
      posthypoxic reoxygenation. The expression of the majority of hypoxia-induced
      proteins was reduced toward control levels during reoxygenation. The most
      prominent changes were identified for glycolytic enzymes (e.g., phosphoglycerate
      kinase), proteins of the ER (e.g., calreticulin), and cytoskeletal (e.g.,
      vimentin) proteins. The results indicate that BCEC respond to
      hypoxia/reoxygenation by adaptive up-regulation of proteins involved in the
      glycolysis, protein synthesis, and stress response.

PMID- 16447159
TI  - Proteomic analysis of beryllium-induced genotoxicity in an Escherichia coli
      mutant model system.
AB  - Beryllium is the second lightest metal, has a high melting point and high
      strength-to-weight ratio, and is chemically stable. These unique chemical
      characteristics make beryllium metal an ideal choice as a component material for
      a wide variety of applications in aerospace, defense, nuclear weapons, and
      industry. However, inhalation of beryllium dust or fumes induces significant
      health effects, including chronic beryllium disease and lung cancer. In this
      study, the mutagenicity of beryllium sulfate (BeSO(4)) and the comutagenicity of
      beryllium with a known mutagen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) were
      evaluated using a forward mutant detection system developed in Escherichia coli.
      In this system, BeSO(4) was shown to be weakly mutagenic alone and significantly
      enhanced the mutagenicity of MNNG up to 3.5-fold over MNNG alone. Based on these
      results a proteomic study was conducted to identify the proteins regulated by
      BeSO(4). Using the techniques of 2-DE and oMALDI-TOF MS, we successfully
      identified 32 proteins being differentially regulated by beryllium and/or MNNG in
      the E. coli test system. This is the first study to describe the proteins
      regulated by beryllium in vitro, and the results suggest several potential
      pathways for the focus of further research into the mechanisms underlying
      beryllium-induced genotoxicity.

PMID- 16447160
TI  - The phosphate-starvation response in Vibrio cholerae O1 and phoB mutant under
      proteomic analysis: disclosing functions involved in adaptation, survival and
      virulence.
AB  - A proteomic analysis of a wild-type and of a phoB mutant showed that Vibrio
      cholerae expresses genes of two major regulons in response to phosphate
      starvation. The Pho regulon, expressed by the wild-type, allowed the cells to
      adapt to the new environment. Induction of the general stress regulon was mainly
      observed in the phoB mutant as a strategy to resist stress and survive. Some
      functions of the adaptative and survival responses play roles in the
      pathogenicity of the bacteria. Among the members of the Pho regulon, we found a
      porin described as an important factor for the intestinal colonisation. Other
      functions not obviously related to phosphate metabolism, expressed preferentially
      by the wild-type cells, have also been implicated in virulence. These findings
      might explain the lack of virulence of the phoB mutant. The Pho regulon picture
      of V. cholerae, however, will not be complete until minor members and membrane
      proteins are identified. Among the phosphate-starvation induced genes we have
      found 13 hypothetical ones and for some of them functions have been assigned. The
      majority of the genes identified here have not been described before, thus they
      could be used to expand the proteomic reference map of V. cholerae El Tor.

PMID- 16447161
TI  - Protein profiling the effects of in vitro hyperoxic exposure on fetal rabbit
      lung.
AB  - The aim of this study was to test the hypothesis that acute in vitro exposure of
      prematurely delivered fetal rabbit lungs to hyperoxic conditions will induce the
      expression of an adaptive cassette of proteins that mediates antioxidant and
      inflammatory processes. To test this hypothesis, ex situ fetal rabbit lung
      explants were prepared from New Zealand white rabbits delivered by cesarean
      section on day 29 of gestation and incubated under air (21% O2; 5% CO2) or
      hyperoxic (95% O2; 5% CO2) atmospheres. Total tissue protein was extracted
      following incubation and subjected to 2-DE. Using this technique, 1500-2000
      protein spots were resolved per gel. Treatment-dependent, differentially
      expressed proteins were identified by image analysis (Melanie II) and MALDI-TOF
      MS and MALDI-MS/MS. The analysis identified 12 protein spots that were
      differentially expressed by 1.5-fold or more (p<0.05) by exposure to hyperoxic
      conditions. Six of these differentially expressed proteins were identified as
      vimentin, annexin I, inorganic pyrophosphatase, prohibitin, an N-terminal
      fragment of ATP synthase and heat shock protein 27. The data obtained are
      consistent with the roles of these proteins in mediating cellular response to
      oxidative stress and in regulating cell proliferation.

PMID- 16447162
TI  - The tegument surface membranes of the human blood parasite Schistosoma mansoni: a
      proteomic analysis after differential extraction.
AB  - The blood fluke Schistosoma mansoni can live for years in the hepatic portal
      system of its human host and so must possess very effective mechanisms of immune
      evasion. The key to understanding how these operate lies in defining the
      molecular organisation of the exposed parasite surface. The adult worm is covered
      by a syncytial tegument, bounded externally by a plasma membrane and overlain by
      a laminate secretion, the membranocalyx. In order to determine the protein
      composition of this surface, the membranes were detached using a freeze/thaw
      technique and enriched by sucrose density gradient centrifugation. The resulting
      preparation was sequentially extracted with three reagents of increasing
      solubilising power. The extracts were separated by 2-DE and their protein
      constituents were identified by MS/MS, yielding predominantly cytosolic,
      cytoskeletal and membrane-associated proteins, respectively. After extraction,
      the final pellet containing membrane-spanning proteins was processed by liquid
      chromatographic techniques before MS. Transporters for sugars, amino acids, ions
      and other solutes were found together with membrane enzymes and proteins
      concerned with membrane structure. The proteins identified were categorised by
      their function and putative location on the basis of their homology with
      annotated proteins in other organisms.

PMID- 16447163
TI  - Role of Wnts in prostate cancer bone metastases.
AB  - Prostate cancer (CaP) is unique among all cancers in that when it metastasizes to
      bone, it typically forms osteoblastic lesions (characterized by increased bone
      production). CaP cells produce many factors, including Wnts that are implicated
      in tumor-induced osteoblastic activity. In this prospectus, we describe our
      research on Wnt and the CaP bone phenotype. Wnts are cysteine-rich glycoproteins
      that mediate bone development in the embryo and promote bone production in the
      adult. Wnts have been shown to have autocrine tumor effects, such as enhancing
      proliferation and protecting against apoptosis. In addition, we have recently
      identified that CaP-produced Wnts act in a paracrine fashion to induce
      osteoblastic activity in CaP bone metastases. In addition to Wnts, CaP cells
      express the soluble Wnt inhibitor dickkopf-1 (DKK-1). It appears that DKK-1
      production occurs early in the development of skeletal metastases, which results
      in masking of osteogenic Wnts, thus favoring osteolysis at the metastatic site.
      As metastases progress, DKK-1 expression decreases allowing for unmasking of
      Wnt's osteoblastic activity and ultimately resulting in osteosclerosis at the
      metastatic site. We believe that DKK-1 is one of the switches that transitions
      the CaP bone metastasis activity from osteolytic to osteoblastic. Wnt/DKK-1
      activity fits a model of CaP-induced bone remodeling occurring in a continuum
      composed of an osteolytic phase, mediated by receptor activator of NFkB ligand
      (RANKL), parathyroid hormone-related protein (PTHRP) and DKK-1; a transitional
      phase, where environmental alterations promote expression of osteoblastic factors
      (Wnts) and decreases osteolytic factors (i.e., DKK-1); and an osteoblastic phase,
      in which tumor growth-associated hypoxia results in production of vascular
      endothelial growth factor and endothelin-1, which have osteoblastic activity.
      This model suggests that targeting both osteolytic activity and osteoblastic
      activity will provide efficacy for therapy of CaP bone metastases.

PMID- 16447164
TI  - Effects of sandblasting and electrical discharge machining on porcelain adherence
      to cast and machined commercially pure titanium.
AB  - The aim of this study was to determine the effect of sandblasting and electrical
      discharge machining (EDM) on cast and machined titanium surfaces and titanium
      porcelain adhesion. Twenty machined titanium specimens were prepared by
      manufacturer (groups 1 and 2). Thirty specimens were prepared with
      autopolymerizing acrylic resin. Twenty of these specimens (groups 3 and 4) were
      cast with commercially pure titanium and the alpha-case layer was removed. For
      control group (group 5), 10 specimens were cast by using NiCr alloy. Groups 2 and
      4 were subjected to EDM while groups 1, 3, and 5 were subjected to sandblasting.
      Surface examinations were made by using a scanning electron microscope (SEM). A
      low-fusing porcelain was fused on the titanium surfaces, whereas NiCr specimens
      were covered using a conventional porcelain. Titanium-porcelain adhesion was
      characterized by a 3-point bending test. Results were analyzed by Kruskal-Wallis
      and Mann-Whitney U tests. Metal-porcelain interfaces were characterized by SEM.
      The bond strength of control group was higher than that of the titanium-porcelain
      system. There was no significant difference between cast and machined titanium
      groups (p > 0.05). There was no significant difference between EDM and
      sandblasting processes (p > 0.05). The use of EDM as surface treatment did not
      improve titanium-porcelain adhesion compared with sandblasting.

PMID- 16447165
TI  - Mechanical and morphological characterization of homogeneous and bilayered poly(2
      hydroxyethyl methacrylate) scaffolds for use in CNS nerve regeneration.
AB  - Homogeneous and bilayered macroporous poly(2-hydroxyethyl methacrylate), p(HEMA),
      hydrogel scaffolds were examined as possible matrices for nerve regeneration in
      the CNS. An important issue to consider for a CNS scaffold is that it must be
      able to closely mimic the natural tissue it is replacing, while remaining intact,
      and mechanically stable enough to allow for regenerating axons to elongate
      through it. Phase-separated homogeneous and bilayered p(HEMA) scaffolds were
      fabricated, by varying water, crosslinking, and initiating agents; all of which
      directly affected the mechanical properties of the polymer. An increase in water
      concentration resulted in a decrease in the modulus for a given crosslinking and
      initiating concentration for all homogenous scaffolds, but the same result was
      not evident in the bilayered scaffolds. The distinct regions within the bilayered
      scaffolds generate a matrix, containing both a highly porous region with modulus
      values representative of spinal cord tissue, as well as a nonporous region that
      provides overall mechanical stability to the entire implant. The overall result
      is a composite matrix for possible use in CNS nerve regeneration, which mimics
      the mechanical properties of spinal tissue, but can withstand the forces that it
      will be subjected to in the injury site.

PMID- 16447166
TI  - Effect of irradiation mode on polymerization of dental composite resins.
AB  - Many researchers have sought to reduce the polymerization shrinkage in composite
      resins. Controlling the irradiation light seems practical because the
      polymerization process initiates with light by activating the photoinitiators.
      The present study evaluated the effect of irradiation mode on microhardness and
      polymerization shrinkage of composite resins. Three different irradiation modes,
      STD, EXP, and MED, were taken under 40-s exposure condition. As results, the
      irradiation mode significantly affected the microhardness difference. However, in
      all products, the microhardness difference between the STD and MED modes was less
      than 10%. In all irradiation modes, microhardness was linearly correlated with
      the filler content of the tested specimens. The effect of mode on the difference
      of the polymerization shrinkage was not uniform even though the shrinkage values
      decreased following the order of the STD > EXP > MED mode. An inverse correlation
      was found between filler content and polymerization shrinkage in all irradiation
      modes and specimen thicknesses. In spite of the statistical significance of the
      irradiation modes on the difference of the measured values, their numeric
      difference was not great. Especially, compared with the STD and MED mode, the
      exponentially increasing light (EXP mode) produced no noticeable difference
      except for a delayed shrinkage process.

PMID- 16447167
TI  - Physics of polypeptide multilayer films.
AB  - Polypeptide multilayer films are promising for the development of coatings for
      implant devices, biosensors, and artificial cells. This paper discusses aspects
      of the physics of these films. Three sub-topics in the physics of peptide
      adsorption in multilayer film assembly covered here are peptide structure at the
      film/solid support interface, adsorbed layer thickness, and dynamics of peptide
      adsorption. A synopsis of work in these areas is preceded by an introduction to
      the subject and a review of some aspects of polymer theory.

PMID- 16447168
TI  - Dual hydroxyapatite composite with porous and solid parts: experimental study
      using canine lumbar interbody fusion model.
AB  - Hydroxyapatite (HA) has been evaluated for use in a variety of applications in
      bone reconstruction surgery because of its high affinity with host bone and
      biocompatibility. However, because of the difficulty in combining porosity (for
      bone ingrowth) and strength in HA, it is generally considered inappropriate to
      use HA for high-load applications such as spinal interbody fusion. In the present
      study, we constructed a HA implant for spinal interbody fusion, composed of a
      dual HA composite (DHC) that combines two HA materials with different porosities:
      HA with 75% porosity, for bone ingrowth; and HA with 0% porosity, for load
      bearing. We used a canine lumbar interbody fusion model to evaluate bone
      conduction of the implant and its efficacy for bony fusion. Six months after the
      operation, DHC exhibited almost the same efficacy for bony fusion as iliac bone
      grafts. Moreover, pores of the porous part of the DHC were completely filled with
      newly formed bone and bone marrow cells. The present findings indicate that DHC
      is suitable for use as an implant material for spinal interbody fusion as a
      substitute for iliac bone grafts, which could eliminate the disadvantages
      associated with autograft harvesting.

PMID- 16447169
TI  - Wear and fatigue behavior of nano-structured dental resin composites.
AB  - Theoretically, nano-structured dental resin composites are purported to have
      increased wear and fatigue resistance compared with microfill composites and may
      favor the achievement of restoratives with better long-term performance. This
      study sought to assess the behavior of nano-structured composites resulting from
      either abrasion and fatigue loading. Ten specimens (12 x 5 x 2.5 mm) were
      prepared from each of five composites: Ceram-X mono, Filtek Supreme, Grandio,
      Premise, and Heliomolar (serving as the microfill control). A surface profile was
      recorded using a three-dimensional profiling system, and the specimens were
      subjected to 10(5) cycles of three-body abrasion in the new OHSU oral wear
      simulator. A second profile was generated and the before and after profiles were
      fit and analyzed. The volume loss and maximum depth of the wear facet on each
      specimen were calculated. Another 30 specimens (25 x 2 x 2 mm) were tested for
      flexural fatigue limit (FFL) in four-point bending via the staircase method. The
      test was carried out until 10(4) cycles were completed or until fracturing the
      specimen. One-way ANOVA and Tukey's test demonstrated greater volumetric loss for
      Grandio and Ceram-X than that observed for the remaining composites. Kruskal
      Wallis and the least significant difference test ascertained that Heliomolar,
      Grandio, and Supreme showed significantly higher FFL than Ceram-X and Premise. In
      terms of wear and fatigue resistance, nano-structured composites may perform
      either similarly or comparatively worse than a microfilled composite.

PMID- 16447170
TI  - New double quantum coherence filter for localized detection of glutathione in
      vivo.
AB  - In this work, a new double quantum filter for glutathione (GSH) editing is
      introduced, combined with the point-resolved spectroscopy localization sequence
      (PRESS), and demonstrated in vivo. Compared to the conventional double quantum
      coherence filter, the new filter has two major advantages. First, it eliminates
      the need for calibration scans for optimizing the signal yield, making it more
      efficient and convenient for routine use. Second, it removes the influence of
      water saturation pulses on the GSH yield, further improving its accuracy. With
      this method, GSH concentrations in the left and right parietal lobes of five
      healthy volunteers were determined to be 0.91+/-0.16 mM and 0.89+/-0.16 mM,
      respectively, in agreement with previous studies.

PMID- 16447171
TI  - Alternating repetition time balanced steady state free precession.
AB  - A novel balanced SSFP technique for the separation or suppression of different
      resonance frequencies (e.g., fat suppression) is presented. The method is based
      on applying two alternating and different repetition times, TR(1) and TR(2). This
      RF scheme manipulates the sensitivity of balanced SSFP to off-resonance effects
      by a modification of the frequency response profile. Starting from a general
      approach, an optimally broadened stopband within the frequency response function
      is designed. This is achieved with a TR(2) being one third of TR(1) and an RF
      pulse phase increment of 90 degrees . With this approach TR(2) is too short (
      approximately 1 ms) to switch imaging gradients and is only used to change the
      frequency sensitivity. Without a significant change of the spectral position of
      the stopband, TR(1) can be varied over a range of values ( approximately 2.5-4.5
      ms) while TR(2) and phase cycling is kept constant. On-resonance spins show a
      magnetization behavior similar to balanced SSFP, but with maximal magnetization
      at flip angles about 10 degrees lower than in balanced SSFP. The total scan time
      is increased by about 30% compared to conventional balanced SSFP. The new
      technique was applied on phantoms and volunteers to produce rapid, fat suppressed
      images.

PMID- 16447172
TI  - A computational study of the lowest singlet and triplet states of neutral and
      dianionic 1,2-substituted icosahedral and octahedral o-carboranes.
AB  - This work introduces a calibrated B3LYP/6-31G(d) study on the electronic
      structure of singlet and triplet neutral species of 1,2-substituted icosahedral
      1,2-R(2)-1,2-C(2)B(10)H(10) and octahedral 1,2-R(2)-1,2-C(2)B(4)H(4) molecules
      with R = {H, OH, SH, NH(2), PH(2), CH(3), SiH(3)} and their respective dianions
      formed by proton removal on each R group. A variety of small adiabatic singlet
      triplet gaps DeltaE(ST) are obtained from these systems ranging from 2.93 eV (R =
      NH(2)) <or= DeltaE(ST) <or= 3.98 eV (R = SiH(3)) for the icosahedral neutrals and
      1.56 eV (R = NH(2)) <or= DeltaE(ST) <or= 4.13 eV (R = SiH(3)) for the octahedral
      neutrals, these gaps being globally smaller for the dianionic systems, ranging
      from 0.94 eV (R(-) = CH(2) (-)) <or= DeltaE(ST) <or= 2.01 (R(-) = e(-)) for the
      icosahedral dianions 1,2-(R(-))(2)-C(2)B(10)H(10) and 0.91 (R(-) = CH(2) (-))
      <or= DeltaE(ST) <or= 2.41 (R = SiH(2) (-)) for the octahedral dianions 1,2-(R(
      ))(2)--C(2)B(4)H(4) (R(-) = e(-), O(-), S(-), NH(-), PH(-), CH(2) (-), PH(2) (
      )). The different gaps lie within or in the neighborhood of the visible region of
      the electromagetic spectrum. The optimized geometries for the molecular cage
      remain similar in substituted icosahedral and octahedral singlet states, while a
      rich variety of different structures can be found for the optimized triplet
      states.

PMID- 16447173
TI  - Interfacing Pichia pastoris cultivation with expanded bed adsorption.
AB  - For improved interfacing of the Pichia pastoris fed-batch cultivation process
      with expanded bed adsorption (EBA) technique, a modified cultivation technique
      was developed. The modification included the reduction of the medium salt
      concentration, which was then kept constant by regulating the medium conductivity
      at low value (about 8 mS/cm) by salt feeding. Before loading, the low
      conductivity culture broth was diluted only to reduce viscosity, caused by high
      cell density. The concept was applied to a one-step recovery and purification
      procedure for a fusion protein composed of a cellulose-binding module (CBM) from
      Neocallimastix patriciarum cellulase 6A fused to lipase B from Candida antarctica
      (CALB). The modified cultivation technique resulted in lower cell death and
      consequently lower concentration of proteases and other contaminating proteins in
      the culture broth. Flow cytometry analysis showed 1% dead (propidium-stained)
      cells compared to 3.5% in the reference process. During the whole process of
      cultivation and recovery, no proteolysis was detected and in the end of the
      cultivation, the product constituted 87% of the total supernatant protein. The
      lipase activity in the culture supernatant increased at an almost constant rate
      up to a value corresponding to 2.2 g/L of CBM-CALB. In the EBA process, no cell
      adsorbent interaction was detected but the cell density had to be reduced by a
      two-times dilution to keep a proper bed expansion. At flow velocity of 400 cm/h,
      the breakthrough capacity was 12.4 g/L, the product yield 98%, the concentration
      factor 3.6 times, the purity about 90%, and the productivity 2.1 g/L x h.

PMID- 16447174
TI  - Drug encapsulation using supercritical fluid extraction of emulsions.
AB  - The current work was aimed at evaluating a new method, supercritical fluid
      extraction of emulsions (SFEE), for the production of composite (e.g., polymer
      drug) micro- and nanoparticles, intended for application in sustained-release
      drug delivery formulations. Using the proposed method, composite particles were
      obtained, both in a continuous or batch manner by supercritical carbon dioxide
      extraction of oil-in-water (o/w) emulsions. Model drugs indomethacin and
      ketoprofen and biodegradable polymers poly(lactic/glycolic) acid and Eudragit RS
      were used in order to demonstrate the effectiveness of the SFEE process for
      producing these particles. Stable aqueous suspensions of composite micro and
      nanoparticles, having sizes ranging between 0.1 and 2 microm were consistently
      obtained. Emulsion droplet diameter was found to be the major size control
      parameter. Other parameters investigated included polymer and drug concentrations
      in solvent and emulsion solvent fraction. The residual solvent content in the
      particle suspension obtained was consistently below 50 ppm. Standard dissolution
      tests were used to observe the sustained release phenomenon of the composite
      particles. The dissolution profile was characterized in terms of the intrinsic
      dissolution kinetic coefficients taking into account the specific surface area
      and solubility of the particles. It was observed that the kinetic coefficient
      parameter for encapsulated drugs was reduced by 2-4 orders of magnitude when
      compared to the unprocessed drug particles.

PMID- 16447175
TI  - Process simulation in the pharmaceutical industry: a review of some basic
      physical models.
AB  - This study reviews process modeling efforts which have been developed to
      elucidate the fundamental physical process underlying the manufacture and
      delivery of pharmaceutical dosage forms. Within the pharmaceutical industry,
      process models have been applied to a diverse array of physical processes at
      length and time scales that vary by orders of magnitude. As such, both large
      scale continuum and particle-scale discrete approaches will be discussed in this
      study. Challenges associated with the practical application of process models
      within the pharmaceutical industry will be discussed, and opportunities for
      future research will be identified.

PMID- 16447176
TI  - A multiphase microscopic diffusion model for stratum corneum permeability. I.
      Formulation, solution, and illustrative results for representative compounds.
AB  - A two-dimensional microscopic transport model of the stratum corneum (SC)
      incorporating corneocytes of varying hydration and permeability embedded in an
      anisotropic lipid matrix is presented. Results are expressed in terms of a
      dimensionless permeability (P(SC/w)(comp), which is a function of two
      dimensionless parameters, R and sigma. R is a ratio of transbilayer to lateral
      molecular flows within a lipid bilayer and sigma is the ratio of (lateral)
      permeability in the lipid phase, D(lip)K(lip/w), to that in the corneocyte phase,
      D(cor)K(cor/w.) The shape of the dimensionless permeability surface is also
      governed by the arrangement of the SC lipids, where Model 1 represents the
      extreme in which lipid-phase transport can occur with no transbilayer transport,
      whereas Model 2 entails maximum transbilayer transport. Model calculations are
      exemplified by characterizing the skin permeability of four representative
      permeants: water, ethanol, nicotinamide, and testosterone. A comparison with
      experimental steady state permeability and partition data supports that the
      transport properties of the SC lipids are highly anisotropic, with lateral
      diffusivities several orders of magnitude higher than the equivalent diffusivity
      calculated from transbilayer hopping. Nevertheless, the calculations suggest that
      corneocyte-phase transport plays a major role for all four permeants. These
      results confirm our previous calculations on water permeability and present a
      marked contrast to the commonly stated doctrine that the SC transport pathway is
      primarily intercellular.

PMID- 16447178
TI  - Phase equilibria and thermodynamics of p-hydroxybenzoic acid.
AB  - The prevalence of phases and associated solubilities of p-hydroxybenzoic acid
      have been investigated in methanol, acetonitrile, acetic acid, acetone, water,
      and ethyl acetate at temperatures from 10 to 50 degrees C. Thermodynamic data was
      acquired through determination of van't Hoff enthalpy of solution, enthalpy of
      fusion, and melting temperature. Indications of polymorphic enantiotropy were
      found primarily through solubility analysis and FTIR-ATR. A comprehensive
      thermodynamic investigation disclosed correlation between the van't Hoff enthalpy
      of solution and the solubility in different solvents. A higher solubility is
      linked to a lower van't Hoff enthalpy of solution. A thermodynamic analysis to
      discriminate between different solid phases is presented.

PMID- 16447177
TI  - Crystal structure and physical properties of two polymorphs of ropivacaine HCl.
AB  - The crystal structure of two polymorphs of ropivacaine HCl have been determined,
      as well as their relative stability up to 100 degrees C. A geometric restriction
      for a solid-state transition between the two polymorphs has been identified. The
      packing density along the H-bonded chains form the basis for a model explaining
      the kinetic crystallization of the metastable form. The difference in stability
      and physicochemical properties between the two polymorphs can be attributed to
      the difference in crystal structure.

PMID- 16447179
TI  - Diurnal rhythm in the levels of the serotonin 5-HT1A receptors in the crayfish
      eyestalk.
AB  - The crayfish eyestalk (ES) has been postulated as a possible circadian clock. 5
      Hydroxytryptamine (5-HT) has been shown to play the role of a neurotransmitter or
      a modulator in the ES. However, little is known about the 5-HT receptors in the
      ES. The purpose of this work is to determine the specific binding sites using
      [(3)H]8-hydroxy-2(di-n-propylamino)tetralin ([(3)H]8-OH-DPAT), a specific agonist
      of the 5-HT(1A) receptor, and to characterize the diurnal rhythm in the binding
      by an autoradiography procedure in the crayfish ES. Data show the presence of a
      circadian rhythmicity in the level of the 5-HT(1A) receptors, principally in two
      regions: (a) the complex retina (R)-lamina ganglionaris (LG), with the acrophase
      at dusk and (b) the medulla terminalis (MT), where it was in antiphase. It is
      suggested that (1) the expression of levels of 5-HT(1A) receptors is modulated by
      light-dark (LD) cycles, (2) the level of 5-HT(1A) receptors in the R-LG and MT
      are in antiphase during the 24-h cycle, and (3) there is a different mechanism of
      action of LD cycles in each of these two anatomical regions of the crayfish ES.

PMID- 16447180
TI  - Long-term potentiation is associated with changes in synaptic ultrastructure in
      the rat neocortex.
AB  - Long-term potentiation (LTP) in the sensorimotor cortex of freely moving rats has
      been associated with changes in dendritic morphology and dendritic spine density.
      The current research examined changes in synaptic number and ultrastructure
      associated with LTP in this cortical region. LTP was induced over a 1 h period
      and the animals were sacrificed 2 h after the initial stimulation of the LTP
      group. Synapses within the terminal area of the apical dendrites from layer III
      pyramidal neurons were quantified by determining the total number of synapses per
      neuron, the number of excitatory and inhibitory contacts, number of synapses with
      different curvature subtypes, number of perforated synapses, and synaptic length.
      Several changes in synaptic morphology of excitatory synapses were revealed but
      no overall increase in the number of synapses per neuron was evident.
      Specifically, the induction of LTP was associated with an increased number of
      excitatory perforated and concave shaped synapses. Increased numbers of
      perforated concave synapses were also found to be significantly correlated with
      the degree of potentiation in the LTP animals. These and previous results suggest
      similar synaptic changes in both the cortex and hippocampus during the early
      phases of LTP maintenance and distinct synaptic changes during later phases of
      LTP maintenance.

PMID- 16447181
TI  - Basics and applications of solid-state kinetics: a pharmaceutical perspective.
AB  - Most solid-state kinetic principles were derived from those for homogenous phases
      in the past century. Rate laws describing solid-state degradation are more
      complex than those in homogenous phases. Solid-state kinetic reactions can be
      mechanistically classified as nucleation, geometrical contraction, diffusion, and
      reaction order models. Experimentally, solid-state kinetics is studied either
      isothermally or nonisothermally. Many mathematical methods have been developed to
      interpret experimental data for both heating protocols. These methods generally
      fall into one of two categories: model-fitting and model-free. Controversies have
      arisen with regard to interpreting solid-state kinetic results, which include
      variable activation energy, calculation methods, and kinetic compensation
      effects. Solid-state kinetic studies have appeared in the pharmaceutical
      literature over many years; some of the more recent ones are discussed in this
      review.

PMID- 16447182
TI  - Spontaneous pulmonary interstitial emphysema in a term unventilated infant.
AB  - Pulmonary interstitial emphysema (PIE) is a form of air block most frequently
      seen in ventilated preterm infants with severe lung disease; it is rarely
      reported in spontaneously breathing term infants. We report on an infant
      previously diagnosed with laryngomalacia and congestive heart failure and with
      evidence of antenatal stroke before the onset of pulmonary disease. He presented
      at 6 weeks of age with spontaneous pneumothorax. Focal cystic changes were seen
      on imaging studies of the lungs. There was no prior history of mechanical
      ventilation. Prior chest X-rays did not show cystic changes. He subsequently
      underwent resection of the affected lung areas. Pathologic examination revealed
      persistent PIE with cystic expansion, pleural blebs, and reactive pleuritis, as
      well as subpleural air-space enlargement. The patient did well postoperatively
      and was discharged home without further problems. This case demonstrates that PIE
      can occur in an infant without any history of mechanical ventilation, suggesting
      the need for a high index of suspicion for PIE, even in nonventilated and
      spontaneously breathing term neonates. PIE should be included in the differential
      diagnosis of cystic lung lesions in all young infants.

PMID- 16447183
TI  - Prefrontal modulation of working memory performance in brain injury and disease.
AB  - The inter-related cognitive constructs of working memory (WM) and processing
      speed are fundamental components to general intellectual functioning in humans.
      Importantly, both WM and processing speed are highly susceptible to disruption in
      cases of brain injury, neurologic illness, and even in normal aging. A goal of
      this article is to summarize and critique the functional imaging studies of
      speeded working memory in neurologically impaired populations. This review
      focuses specifically on the role of the lateral prefrontal cortex in mediating WM
      performance and integrates the relevant WM literature in healthy adults with the
      current findings in the clinical literature. One important finding emerging from
      a summary of this literature is the dissociable contributions made by
      ventrolateral and dorsolateral prefrontal cortex (VLPFC and DLPFC) in guiding
      performance on tasks of WM. Throughout this review, it is shown that when
      cerebral resources are challenged, it is DLPFC, and often right DLPFC
      specifically, that plays a critical role in modulating WM functioning. In
      addition, this article will examine the relationship between task performance and
      brain activation across studies to clarify the role of increased DLPFC activity
      in clinical samples. Finally, explanations are offered for the observed increased
      DLPFC activation and the potentially unique role of right DLPFC in mediating WM
      performance during periods of cerebral challenge.

PMID- 16447184
TI  - Kinetics of hepatitis C virus reinfection after liver transplantation.
AB  - Improved understanding of hepatitis C virus (HCV) dynamics during and after liver
      transplantation can be useful in optimizing antiviral therapy in transplant
      recipients. We analyzed serum HCV ribonucleic acid (RNA) levels during and after
      cadaveric liver transplantation in 6 HCV patients. After removal of the liver and
      before the new liver started producing virions, HCV RNA levels dropped with an
      average half-life (t(1/2)) of 0.8 hours. Viral loads then continued to drop up to
      23 hours postimplantation (t(1/2) = 3.4 hours), and began to rise (doubling-time
      = 2.0 days) as soon as 15 hours after the anhepatic phase. In 3 patients the
      viral load reached a plateau before rising, suggesting that a nonhepatic source
      supplied virions and balanced their intrinsic clearance. However, from the
      decline in viral load over the first 24 hours of the postanhepatic phase, we
      estimate that nonhepatic sources can at most correspond to 4% of total viral
      production, 96% of which occurs in the liver, even after we corrected for fluid
      exchanges during surgery. As the new liver was reinfected, production increased
      and viral load rose to a new steady state. Using nonlinear regression, we were
      able to fit the patients' HCV RNA data to a viral dynamic model and estimate the
      de novo infection rate (mean 1.5 x 10(-6) mL/virion/day), as well as the average
      percentage of hepatocytes infected at the posttransplantation steady state (19%).
      In conclusion, we have quantified liver reinfection dynamics in the absence of
      posttransplantation antiviral therapy. Our findings support the notion that early
      antiviral therapy may delay or prevent reinfection.

PMID- 16447185
TI  - Low circulating regulatory T-cell levels after acute rejection in liver
      transplantation.
AB  - Immune regulatory CD4+CD25+ T cells play a crucial role in inducing and
      maintaining allograft tolerance in experimental models of transplantation (Tx).
      In humans, the effect of Tx and immunosuppression on the function and homeostasis
      of CD4+CD25+ regulatory T cells (Tregs) is not well characterized. In this study,
      the frequency of Tregs in liver transplant recipients was determined based on
      flow cytometric analysis of CD4, CD25, CD45RO, and cytotoxic T lymphocyte antigen
      (CTLA)-4 markers, and the suppressor activity of Tregs was assessed in a mixed
      leukocyte reaction. A link between Tregs, acute rejection, and immune-suppressive
      treatment was investigated. Liver transplant recipients had significantly higher
      Treg levels in peripheral blood pre-Tx than healthy controls. After Tx, a
      significant drop in the Treg fraction was observed. This reduction of circulating
      Tregs was transient and was associated with immunosuppression. In recipients who
      did not develop rejection, a relative recovery of Treg levels was seen within the
      first year after Tx. Recipients who experienced an episode of steroid-treated
      acute rejection, however, had sustained low Treg levels. The suppressive
      activities of CD4+CD25+ Tregs from rejectors, nonrejectors, and healthy controls
      on proliferation and interferon (IFN)-gamma production were indistinguishable. In
      conclusion, the percentage of CD4+CD25+CD45RO+CTLA-4+ quadruple-positive Tregs in
      peripheral blood decreases significantly after liver Tx. Treatment with
      methylprednisolone during Tx and for acute rejection is associated with low
      circulating Tregs. Despite these quantitative differences between rejectors and
      nonrejectors, the suppressive quality of CD4+CD25+ Tregs is identical in both
      groups.

PMID- 16447187
TI  - Transplantation for alcoholic liver disease: report of a consensus meeting.

PMID- 16447186
TI  - Cyclosporine exposure and calcineurin phosphatase activity in living-donor liver
      transplant patients: twice daily vs. once daily dosing.
AB  - We have compared the pharmacokinetics and pharmacodynamics of cyclosporine
      between once- and twice-daily dosing regimens in de novo patients of living-donor
      liver transplantation (LDLT). A total of 14 patients were enrolled in this study,
      who had received cyclosporine microemulsion (Neoral) twice a day (BID, n = 5) or
      once daily in the morning (QD, n = 9) after transplantation. On postoperative day
      (POD) 6, the QD regimen significantly increased cyclosporine exposure; the blood
      concentration at 2 hours postdose (C2) and area under the concentration-time
      curve (AUC) for 4 hours (AUC(0-4)), compared with the BID regimen. Moreover, the
      area under the calcineurin (CaN) activity in peripheral blood mononuclear cells
      time-curve (AUA) for 12 hours (AUA(0-12)) and 24 hours (AUA(0-24)) were decreased
      by approximately 42 and 25% with the QD regimen relative to the BID regimen,
      respectively. The C2 level was significantly correlated with the AUC(0-4) (r2 =
      0.95), which was negatively related to the AUA(0-12) with a large interindividual
      variability (r(2) = 0.59). However, a significant correlation was found between
      the AUA(0-12) or AUA(0-24) and CaN activity at trough time points. According to a
      maximum inhibitory effect attributable to the drug (E(max)) model, the mean
      estimates of E(max) and the C(b) value that gives a half-maximal effect (EC50)
      for CaN inhibition were not significantly different between the 2 groups,
      respectively. These findings suggest that a once daily morning administration of
      cyclosporine may improve oral absorption and help to provide an effective CaN
      inhibition early after LDLT. Furthermore, CaN activity at trough time points
      would be a single surrogate predictor for the overall CaN activity throughout
      dosing intervals following cyclosporine administration.

PMID- 16447188
TI  - Late presentation of a biliary tract complication after right hepatic donation
      resulting in secondary biliary cirrhosis.

PMID- 16447189
TI  - Clinicopathologic findings and outcomes of liver transplantation using grafts
      from donors with unrecognized and unusual diseases.
AB  - Despite certain strict criteria for suitable organ donors, some unrecognized and
      unusual diseases have been transmitted through liver transplantation to
      recipients. In the current series, we review our experience with 14 patients who
      underwent liver transplantation using donor grafts with unusual pathology,
      including amyloidosis (6), schistosomiasis (3), iron overload (2), and alpha-1
      antitrypsin deficiency (3). One of 6 patients who received grafts with
      amyloidosis developed vasculitis associated with the presence of arterial
      amyloid. With proper management, patients with donor schistosomiasis, iron
      overload and alpha-1 antitrypsin deficiency appear to have outcomes comparable to
      liver transplantation using grafts without these findings. In conclusion, long
      term follow-up is necessary to confirm these findings and understand the impact
      of using these grafts.

PMID- 16447190
TI  - Indications for chronic albumin infusion.

PMID- 16447191
TI  - Immunization with an adjuvant hepatitis B vaccine in liver transplant recipients:
      antibody decline and booster vaccination with conventional vaccine.
AB  - Patients after orthotopic liver transplantation (OLT) due to hepatitis B virus
      (HBV)-related disease are at risk of endogenous hepatitis B reinfection and may
      receive life long prophylaxis with hepatitis B hyperimmunoglobulin (HBIG). In a
      previous study 16 of 20 OLT patients were immunized successfully with an adjuvant
      hepatitis B vaccine. To maintain protective antibody levels under
      immunosuppressive therapy, 11 of these patients were revaccinated with a double
      dosed conventional hepatitis B vaccine. Median interval between last vaccination
      and booster was 24 months (range 22-31 months). Antibody titres against hepatitis
      B surface antigen (anti-HBs) were monitored at the day of booster vaccination
      (day 0), at day 7 and day 28. At day 0, all vaccinees but one had anti-HBs titres
      greater than 500 IU/L (median 1,925 IU/L, range 196-7,612 IU/L). Maximum antibody
      titres after previous vaccination declined by a median of 82% (range 47-96%).
      After booster vaccination the anti-HBs titre increased significantly by a median
      factor of 2.42 (P<0.05). In conclusion, the majority of liver transplant
      recipients who previously had responded to adjuvant hepatitis B vaccine exhibited
      sufficient immunocompetence to produce a substantial antibody response after
      booster immunization with a conventional vaccine.

PMID- 16447192
TI  - Preemptive therapy for cytomegalovirus.

PMID- 16447193
TI  - Abdominal imaging and intervention in liver transplantation.
AB  - Diagnostic imaging and interventional radiology play key roles in the evaluation
      and management of patients who are being evaluated for potential liver
      transplantation (LTX) and of those who have received a transplanted liver.
      Technical advances in imaging equipment and technique allow more accurate
      assessment and often obviate unnecessary or nontherapeutic surgery or invasive
      techniques such as catheter angiography.

PMID- 16447194
TI  - Perioperative viral kinetics: new insights or the Emperor's new clothes?

PMID- 16447195
TI  - Prevention of hepatitis B recurrence after liver transplantation using lamivudine
      or lamivudine combined with hepatitis B Immunoglobulin prophylaxis.
AB  - The aim of our study was to determine the outcomes of liver transplant recipients
      receiving either lamivudine (LAM) monotherapy or LAM combined with low-dose
      intramuscular (IM) hepatitis B Immunoglobulin (HBIG) therapy. We performed a
      retrospective review of the medical records of patients that had had liver
      transplantation in a single center for HBV-related liver diseases from December
      1999 to June 2004. A total of 165 patients received LAM monotherapy (51 patients)
      or combined prophylaxis (114 patients) post-liver transplantation (LT) with a
      mean follow-up of 20.13 months. Hepatitis B relapsed in 21 patients of the
      hepatitis B surface antigen (HBsAg) carriers who received LAM monotherapy, with a
      1- and 2-yr actuarial risk of 27.4% and 39.7%. Recurrence occurred in 16 patients
      of 114 patients receiving the combined prophylaxis, with a 1- and 2-yr recurrence
      rate of 13.5% and 15.2% (P = 0.024). A total of 25 cases (67.6%) with YMDD
      mutants were detected in all the 37 patients, 14 cases (66.7%) in the monotherapy
      group and 11 cases (68.8%) in the combination group. In conclusion, LAM and low
      dose intramuscular HBIG treatment demonstrates a better result than LAM
      monotherapy, as prophylaxis against post-LT reinfection of the graft, but the
      safety and efficacy as a substitution for high-dose intravenous HBIG with LAM
      needs to be investigated further.

PMID- 16447196
TI  - Long-term biological consequences of donor right hepatectomy including the middle
      hepatic vein in adult-to-adult live donor liver transplantation.
AB  - The right lobe liver graft has become the workhorse of adult-to-adult live donor
      liver transplantation. Donor right hepatectomy is feasible only because of the
      immense regenerative ability of the liver. The long-term biological consequences
      of this very major donor procedure on the donor however are unknown. Twenty-nine
      donors of this procedure in our centre, all of whom included the middle hepatic
      vein, were studied. On long-term follow-up at a median of 47.4 months, there was
      a discernible but statistically insignificant decrease in size of the regenerated
      left lobe compared to the original whole liver volume. There was paradoxically a
      trend of incompleteness of regeneration in relation to the original liver volume
      for those with a larger remnant left lobe. The volume ratio of the regenerated
      left lobe to the original left lobe before hepatectomy was inversely proportional
      to the left lobe proportion preoperatively. This strong but inverse linear
      correlation reflected the good regenerative ability of the remnant left lobe.
      None of the donors developed thrombocytopenia. Although demonstrable decrease in
      white cell count, increase in serum alanine aminotransferase, aspartate
      aminotransferase, and creatinine did occur, the changes remained within normal
      limits and were of yet uncertain clinical significance. In conclusion, donor
      right hepatectomy including the middle hepatic vein is biologically acceptable to
      the live donor.

PMID- 16447197
TI  - Endovascular stent placement for interposed middle hepatic vein graft occlusion
      after living-donor liver transplantation using right-lobe graft.
AB  - Middle hepatic vein (MHV) reconstruction is performed to drain the right
      paramedian sector to prevent hepatic venous congestion (HVC). The aim of the
      present study was to evaluate endovascular stent placement in patients with
      stenosed and/or occluded interposition vein graft (IVG) to segment V hepatic vein
      (V5) and segment VIII hepatic vein (V8) after living-donor liver transplantation
      (LDLT). The procedure was performed in 11 recipients; 7 underwent it within 24
      hours of LDLT. The following parameters, including technical success, clinical
      success, complications, patient survival data, and serial computed tomography
      (CT) findings during follow-up, were documented retrospectively. Technical
      success was defined as both successful stent placement and resolution of stenosis
      or occlusion with copious flow of contrast medium through the stent, while
      clinical success was defined as both improvement of liver function tests (LFTs)
      and reduction or disappearance of hepatic low-attenuation areas on follow-up CT
      scans taken within 1 week of stent placement. Technical success was achieved in
      10 of 11 patients (91%), and clinical success was achieved in 9 of 11 patients
      (82%). Acute thrombotic occlusion of the stent-inserted hepatic vein occurred in
      1 patient 1 day following stent placement. During the mean follow-up period of
      468 days (range, 13-891 days), 9 patients survived and 2 patients died. No death
      was directly related to stent placement or its related complications. The low
      attenuation area in the involved hepatic segment V (S5) and/or VIII (S8) area
      prior to stent placement disappeared completely on follow-up CT scans performed
      at 3-12 days (mean, 5.4 days) after stent placement in all 9 patients with
      clinical success. No attenuation change occurred even in cases with chronic
      occlusion of the stent-inserted hepatic veins. In conclusion, though IVG to V5
      and V8 remains controversial, the treatment of their stenosis or occlusion is
      safe and effective, even during their immediate postoperative period.

PMID- 16447198
TI  - Cystatin C as a marker of renal function immediately after liver transplantation.
AB  - To verify whether cystatin C may be of some use as a renal function marker
      immediately after orthotopic liver transplantation (OLT), we compared serum
      cystatin C (S(Cyst)), serum creatinine (S(cr)), and creatinine clearance (C(cr))
      levels with the glomerular filtration rate (GFR). On postoperative days 1, 3, 5,
      and 7, S(Cyst) and S(cr) was measured in simultaneously drawn blood samples,
      whereas C(cr) was calculated using a complete 24-hour urine collection. The GFR
      was determined on the same days by means of iohexol plasma clearance (I-GFR). The
      correlation between 1/S(Cyst) and I-GFR was stronger than that of 1/S(cr) or
      C(cr) (P< 0.01). In the case of moderate reductions in I-GFR (80-60
      mL/minute/1.73 m), S(cr) remained within the normal range, whereas the increase
      in S(cyst) was beyond its upper limit; for I-GFR reductions to lower levels (59
      40 mL/minute/1.73 m), S(cr) increased slightly, whereas S(cyst) was twice its
      upper normal limit. When we isolated all of the I-GFR values on days 3, 5, and 7
      that were > or = 30% lower than that recorded on the first postoperative day,
      S(Cyst)(P< 0.0001) and S(cr) (P< 0.01) levels were increased, whereas C(cr)
      remained unchanged (P = 0.09). Receiver operating characteristic (ROC) area-under
      the-curve analysis showed that the diagnostic accuracy of S(cyst) was better than
      that of S(cr) and C(cr). S(cyst) levels of 1.4, 1.7, and 2.2 mg/L respectively
      predicted I-GFR levels of 80, 60, and 40 mL/minute/1.73 m. In conclusion,
      cystatin C is a reliable marker of renal function during the immediate post-OLT
      period, especially when the goal is to identify moderate changes in GFR.

PMID- 16447199
TI  - Caval preservation with reconstruction of the hepatic veins using caval-common
      iliac bifurcation graft for domino liver transplantation.

PMID- 16447200
TI  - Cytomegalovirus in liver transplant recipients: there are many ways to Rome.

PMID- 16447201
TI  - Outcome of donors with a remnant liver volume of less than 35% after right
      hepatectomy.
AB  - To overcome the barrier of size match, right lobe graft has been widely used in
      living donor liver transplantation (LDLT). We assessed donor outcome, with a
      focus on remnant liver volume (RLV) after right hepatectomy based on the
      experiences of 2 LDLT centers, as a means of guiding the establishment of safe
      RLV limits for donor right hepatectomy. Between January 2002 and December 2003, a
      consecutive 146 liver donors who underwent right hepatectomy with at least 12
      months of follow-up were enrolled in this study. Donors were grouped into 2
      groups according to RLV: group 1 (n = 74), <35% (range, 26.9-34.9) and group 2 (n
      = 72), > or = 35% (35.0-46.8). No donors died or suffered a life-threatening
      complication. Mean peak serum postoperative aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) (IU/L) levels were 219.5 +/- 79.9 and 231.5 +/-
      83.3 in group 1 and 210.3 +/- 81.6 and 225.8 +/- 93.0 in group 2 (P = 0.497 and
      0.699), respectively. Mean peak serum total bilirubin (TB) (mg/dL) level in group
      1 (3.4 +/- 1.6) was higher than in group 2 (2.8 +/- 1.4; P = 0.023). Overall 23
      (15.8%) major morbidities, 10 in group 1 (13.5%) and 13 in group 2 (18.1%),
      occurred according to Clavien's system (P = 0.939). These included bleeding (n =
      3 in group 1 and n = 6 in group 2; P = 0.282), ileus (n = 3 and 1; P = 0.324),
      biliary leakage (n = 4 and 4; P = 0.968), and pneumonia (n = 0 and 2; P = 0.149).
      Minor morbidities were also comparable in the 2 groups. In conclusion, the
      outcome of donors with an RLV of <35% was not different from that of donors with
      an RLV of > or = 35%, with the exception of transient cholestasis. Therefore, a
      remnant RLV of <35% does not appear to be a contraindication for right liver
      procurement in living donors.

PMID- 16447202
TI  - Warm ischemia-reperfusion injury is decreased by tacrolimus in steatotic rat
      liver.
AB  - Ischemia-reperfusion (I-R) injury is poorly tolerated by fatty livers, most
      probably secondary to reduced cellular adenosine triphosphate (ATP) levels. We
      investigated the effectiveness of tacrolimus pretreatment on fatty liver I-R
      injury in obese Zucker rats. Tacrolimus (0.3 mg/kg, intravenously) was injected
      24 hours before a 75-minute ischemic period and rats were sacrificed 6 hours
      later. Tacrolimus modified the response to I-R observed in obese Zucker rats,
      when compared to nontreated obese rats: a significant reduction in hepatocyte
      necrosis was associated with a significant increase in hepatocyte apoptosis. In
      addition, cell necrosis and apoptosis were significantly and inversely correlated
      in lean nontreated and treated obese Zucker rats following I-R. Tacrolimus also
      significantly increased the hepatic ATP levels, reduced in nontreated obese rats,
      toward values found in lean Zucker rat livers. This protective effect of
      tacrolimus was further confirmed in vivo by a significantly improved survival
      following pretreatment with tacrolimus, 24 hours prior to ischemia. In
      conclusion, in obese Zucker rat livers, tacrolimus pretreatment reversed the I-R
      injury toward the one found in lean Zucker rats. The correlations between ATP
      levels and the opposite changes in necrosis and apoptotic pathways strongly
      suggest a cause-effect relationship between tacrolimus and changes in ATP levels.

PMID- 16447203
TI  - Comparison of histidine-tryptophan-ketoglutarate solution (HTK) and University of
      Wisconsin solution (UW) in adult liver transplantation.
AB  - Histidine-tryptophan-ketoglutarate solution (HTK) and University of Wisconsin
      solution (UW) have been shown to have similar outcomes in cadaveric kidney,
      pancreas, and liver transplantation. Our institution changed from UW to HTK as
      the primary preservation solution for liver, kidney and pancreas transplantation.
      This study compares the perioperative and first year outcomes of liver
      transplantation using UW or HTK. Primary use of HTK began on May 1, 2003. We
      reviewed the records of all adult liver transplant recipients from July 1, 2002
      to December 31, 2004. Recipients were compared based on organ preservation
      solution (UW n = 204, HTK n = 174). Outcomes included 1-, 6- and 12-month graft
      and patient survival and 1-, 7-, 14-, and 30-day liver function and serum
      creatinine. During the entire study period, the two groups were managed similarly
      in operative technique, immunosuppressive regimens, and donor liver criteria.
      Over 30 months, 378 adult patients underwent liver transplantation. There were no
      significant differences between UW and HTK in 1-, 6-, or 12-month graft or
      patient survival. The HTK group had a higher day 1 median AST, ALT, and total
      bilirubin, but the two groups were similar thereafter. An anticipated difference
      in infused volume between UW and HTK was demonstrated. In conclusion, to our
      knowledge, this is the first reported large case series from North America
      comparing HTK and UW in liver transplantation with 2- to 12-month follow-up.
      There were no significant differences between HTK and UW in this population when
      comparing 1 month graft function and first-year graft and patient survival.

PMID- 16447204
TI  - Allograft TNFbeta and IL16 polymorphisms influence HCV recurrence and severity
      after liver transplantation.
AB  - Hepatitis C (HCV) recurrence after liver transplantation is universal although
      severity varies. We explored whether certain donor cytokine gene polymorphisms
      may be useful markers of susceptibility to severe recurrence. Allograft tumor
      necrosis factor (TNF) beta and interleukin (IL) 16 gene polymorphisms were
      correlated with l-yr clinical outcome among HCV+ recipients. Recipients of donor
      TNFbeta(2,2) (n = 8) experienced less recurrence (50% vs. 71%, P < 0.05), less
      fibrosis (25% vs. 76%, P < 0.01), and less rejection (25% vs. 71%, P < 0.01) than
      donor TNFbeta(1,1) (n = 19). Recipients of donor TNFbeta(1,2) (n = 27)
      demonstrated an intermediate picture with less fibrosis (56%, P < 0.01) and less
      rejection (37%, P < 0.01) than TNFbeta(1,1). Recipients with donor IL16(TC) (n =
      22) showed less recurrence (65% vs. 78%, P = 0.05), less fibrosis (53% vs. 67%, P
      = 0.06), and less rejection (41% vs. 55%, P = 0.06) than IL16(TT) (n = 32)
      genotype. Recipients of the combination TNFbeta(2,2)/IL16(TC) donor genotype had
      the most benign clinical outcome with less recurrence (33% vs. 75%, P < 0.01), no
      fibrosis (0% vs. 50%, P < 0.001), and fewer rejections (33% vs. 75%, P < 0.01)
      than donor TNFbeta(1,1)/IL16(TT) genotype. In vitro production of cytokines
      correlated with genotype. Release of soluble TNFbeta for TNFbeta(1,1) vs.
      TNFbeta(1,2) and TNFbeta(2,2) was 4803 +/- 2142 pg/mL vs. 5629 +/- 3106 (P = not
      significant [ns]) and 7180 +/- 3005 (P = ns). Release of soluble IL16 for
      IL16(TT) vs. IL16(TC) was 437 +/- 86 pg/mL vs. 554 +/- 39 (P = 0.06). In
      conclusion, allograft TNFbeta and IL16 gene polymorphisms may be useful markers
      to predict the severity of disease recurrence among HCV+ patients after liver
      transplantation.

PMID- 16447205
TI  - Donor graft outflow venoplasty in living donor liver transplantation.
AB  - Hepatic venous outflow reconstruction is a key to successful living donor liver
      transplantation (LDLT) because its obstruction leads to graft dysfunction and
      eventual loss. Inclusion or reconstruction of most draining veins is ideal to
      ensure graft venous drainage and avoids acute congestion in the donor graft. We
      developed donor graft hepatic venoplasty techniques for multiple hepatic veins
      that can be used in either right- or left-lobe liver transplantation. In left
      lobe grafts, venoplasty consisting of the left hepatic vein and adjacent veins
      such as the left superior vein, middle hepatic vein, or segment 3 vein is
      performed to create a single, wide orifice without compromising outflow for
      anastomosis with the recipient's vena cava. In right lobe graft where a right
      hepatic vein (RHV) is adjacent with a significantly-sized segment 8 vein,
      accessory RHV, and/or inferior RHV, venoplasty of the RHV with the accessory RHV,
      inferior RHV, and/or segment 8 vein is performed to create a single orifice for
      single outflow reconstruction with the recipient's RHV or vena cava. Of 35
      venoplasties, 2 developed hepatic venous stenoses which were promptly managed
      with percutaneous interventional radiologic procedures. No graft was lost due to
      hepatic venous stenosis. In conclusion, these techniques avoid interposition
      grafts, are easily performed at the back table, simplify graft-to-recipient cava
      anastomosis, and avoid venous outflow narrowing.

PMID- 16447207
TI  - Preservation solutions in liver transplantation: what are the options?

PMID- 16447208
TI  - Living donor liver transplantation in high-risk vs. low-risk patients:
      optimization using statistical models.
AB  - Living donors represent a recognized alternative for facilitating the access to
      transplantation in a period of organ shortage. However, which candidates should
      be preferentially considered for living-donor liver transplantation (LDLT) is
      debated. The aim of this study was to create statistical models to determine
      which strategies of selection for LDLT provide the most efficient contribution.
      The study included 331 patients listed for deceased-donor transplantation (DDLT)
      and 128 transplanted with living donors. Statistical models predicting the events
      following listing were created and combined in a multistate model allowing the
      testing of different strategies of selection for LDLT and to compare their
      results. Taking 3-yr survival after listing as the principal end-point, selecting
      the 20% patients at highest risk of death on the waiting list gave better results
      than selecting the 20% patients at lowest risk of death after LDLT (70% vs. 64%,
      respectively). These strategies resulted in waiting list mortality rates of 17%
      and 8%, respectively. One-year survival after LDLT was lower in high-risk
      patients (85%) than in low-risk patients (91%). However, the 1-yr survival
      benefit derived from LDLT was 75% in high-risk patients while it was nil in low
      risk patients. In conclusion, LDLT is more effective for overcoming the
      consequences of organ shortage when performed in patients at high risk of death
      on the waiting list. On an individual basis, the sickest patients are those who
      derive the most important benefit from LDLT. This study provides incentives for
      considering LDLT in high-risk patients.

PMID- 16447209
TI  - Cyclosporine A withdrawal during follow-up after pediatric liver transplantation.
AB  - It is unclear whether cyclosporine A (CsA) can be withdrawn safely during follow
      up after pediatric liver transplantation. In our transplant program we have been
      using a strict protocol to withdraw CsA. The aim of this study was to
      retrospectively assess the effects of CsA withdrawal after pediatric liver
      transplantation on the incidence of rejection and renal function. Between 1986
      and 2001, 91 children received CsA for at least 2 yr after liver transplantation.
      Specific criteria for eligibility to withdraw CsA were set. In 53 of the 91
      children CsA was withdrawn. In 35 patients (66%) withdrawal of CsA did not cause
      rejection. In these patients the renal function improved compared with baseline
      values (glomerular filtration rate (GFR) at 1 yr, +16 mL/minute/1.73 m3, P <
      0.001; at 2 yr, +10 mL/minute/1.73 m3, P < 0.05). After CsA withdrawal, 18
      patients developed rejection (34%), which could be effectively treated by
      methylprednisolone and restarting CsA. Failure to withdraw CsA was not associated
      with increased incidence of graft loss. A body weight below 10 kg at the time of
      transplantation correlated significantly with successful withdrawal of CsA (<10
      kg, 85% vs. > 10 kg, 60%; P < 0.05). In conclusion CsA can successfully be
      withdrawn in a major proportion of selected pediatric liver transplantation
      patients during follow-up. The success rate is the highest in children with a
      body weight below 10 kg at the time of transplantation. Successful withdrawal
      improves renal function, whereas failure to withdraw is not associated with graft
      loss or persisting morbidity.

PMID- 16447210
TI  - Extended follow-up of extended right lobe living donors: when is enough enough?

PMID- 16447211
TI  - How does spatial extent of fMRI datasets affect independent component analysis
      decomposition?
AB  - Spatial independent component analysis (sICA) of functional magnetic resonance
      imaging (fMRI) time series can generate meaningful activation maps and associated
      descriptive signals, which are useful to evaluate datasets of the entire brain or
      selected portions of it. Besides computational implications, variations in the
      input dataset combined with the multivariate nature of ICA may lead to different
      spatial or temporal readouts of brain activation phenomena. By reducing and
      increasing a volume of interest (VOI), we applied sICA to different datasets from
      real activation experiments with multislice acquisition and single or multiple
      sensory-motor task-induced blood oxygenation level-dependent (BOLD) signal
      sources with different spatial and temporal structure. Using receiver operating
      characteristics (ROC) methodology for accuracy evaluation and multiple regression
      analysis as benchmark, we compared sICA decompositions of reduced and increased
      VOI fMRI time-series containing auditory, motor and hemifield visual activation
      occurring separately or simultaneously in time. Both approaches yielded valid
      results; however, the results of the increased VOI approach were spatially more
      accurate compared to the results of the decreased VOI approach. This is
      consistent with the capability of sICA to take advantage of extended samples of
      statistical observations and suggests that sICA is more powerful with extended
      rather than reduced VOI datasets to delineate brain activity.

PMID- 16447212
TI  - Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship
      to extraarticular disease manifestations.
AB  - OBJECTIVE: To investigate the incidence of noncardiac vascular disease in
      patients with rheumatoid arthritis (RA) and its relationship to systemic
      extraarticular disease in a community-based cohort. METHODS: A retrospective
      medical record review of 609 patients with incident RA diagnosed during 1955-1994
      was carried out in Olmsted County, Minnesota. Patients were followed up from 1955
      to 2000 (median followup 11.8 years). Incident noncardiac vascular disease and
      severe extraarticular RA manifestations (including pericarditis, pleuritis, and
      vasculitis) were recorded according to predefined criteria, and incidence rates
      were estimated. Using Cox proportional hazards models, the risk (hazard ratio
      [HR]) of developing vascular events was assessed in patients with and without
      severe extraarticular RA. RESULTS: Cerebrovascular and peripheral arterial events
      occurred in 139 patients (22.8%). The 30-year cumulative incidence rates of
      peripheral arterial events, cerebrovascular events, and venous thromboembolic
      events were estimated to be 19.6%, 21.6%, and 7.2%, respectively. The presence of
      severe extraarticular RA manifestations was found to be associated with all
      subgroups of noncardiac vascular disease except cerebrovascular disease alone (HR
      2.3, 95% confidence interval [95% CI] 1.2-4.3 for peripheral arterial events; HR
      3.7, 95% CI 1.3-10.3 for venous thromboembolic events; HR 1.5, 95% CI 0.7-3.2 for
      cerebrovascular events) after adjusting for age, sex, body mass index, smoking,
      and rheumatoid factor status. CONCLUSION: This is the first study to assess the
      incidence of noncardiac vascular disease in RA. Severe extraarticular RA was
      associated with all forms of noncardiac vascular disease except cerebrovascular
      disease alone. Similar to cardiac disease, the excess risk of noncardiac vascular
      disease in RA is likely to be related, in part, to the systemic inflammation
      associated with the extraarticular manifestations of RA.

PMID- 16447213
TI  - Evil humors take their toll as innate immunity makes gouty joints TREM-ble.

PMID- 16447214
TI  - Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo
      transduction of muscle-derived stem cells.

PMID- 16447215
TI  - Potential antiinflammatory and immunomodulatory effects of statins in
      rheumatologic therapy.

PMID- 16447216
TI  - Statins as antiinflammatory and immunomodulatory agents: a future in
      rheumatologic therapy?

PMID- 16447217
TI  - The type I interferon system in systemic lupus erythematosus.

PMID- 16447218
TI  - Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem
      cells.
AB  - OBJECTIVE: Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle
      exhibit long-time proliferation, high self-renewal, and multipotent
      differentiation. This study was undertaken to investigate the ability of MDSCs
      that were retrovirally transduced to express bone morphogenetic protein 4 (BMP-4)
      to differentiate into chondrocytes in vitro and in vivo and enhance articular
      cartilage repair. METHODS: Using monolayer and micromass pellet culture systems,
      we evaluated the in vitro chondrogenic differentiation of LacZ- and BMP-4
      transduced MDSCs with or without transforming growth factor beta1 (TGFbeta1)
      stimulation. We used a nude rat model of a full-thickness articular cartilage
      defect to assess the duration of LacZ transgene expression and evaluate the
      ability of transplanted cells to acquire a chondrocytic phenotype. We evaluated
      cartilage repair macroscopically and histologically 4, 8, 12, and 24 weeks after
      surgery, and performed histologic grading of the repaired tissues. RESULTS: BMP-4
      expressing MDSCs acquired a chondrocytic phenotype in vitro more effectively than
      did MDSCs expressing only LacZ; the addition of TGFbeta1 did not alter
      chondrogenic differentiation of the BMP-4-transduced MDSCs. LacZ expression
      within the repaired tissue continued for up to 12 weeks. Four weeks after
      surgery, we detected donor cells that coexpressed beta-galactosidase and type II
      collagen. Histologic scoring of the defect sites 24 weeks after transplantation
      revealed significantly better cartilage repair in animals that received BMP-4
      transduced MDSCs than in those that received MDSCs expressing only LacZ.
      CONCLUSION: Local delivery of BMP-4 by genetically engineered MDSCs enhanced
      chondrogenesis and significantly improved articular cartilage repair in rats.

PMID- 16447220
TI  - Induction of triggering receptor expressed on myeloid cells 1 in murine resident
      peritoneal macrophages by monosodium urate monohydrate crystals.
AB  - OBJECTIVE: Triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell
      surface molecule that was recently identified on monocytes and neutrophils. TREM
      1 has been implicated in the early inflammatory responses induced by microbes,
      but its pathophysiologic role in nonmicrobial inflammation remains unknown. In
      the present study, we investigated the role of TREM-1 in acute inflammation
      induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM-1
      expression by MSU crystal-stimulated murine resident peritoneal macrophages and
      infiltrating leukocytes in a murine air-pouch model of crystal-induced acute
      inflammation was determined. The biologic role of TREM-1 in crystal-induced
      cytokine production by resident peritoneal macrophages was also investigated.
      METHODS: TREM-1 expression by resident peritoneal macrophages and infiltrating
      leukocytes in a murine air-pouch model was determined by quantitative real-time
      polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine
      production by resident peritoneal macrophages after incubation with MSU crystals
      in the presence or absence of an anti-TREM-1 agonist antibody was determined by
      enzyme-linked immunosorbent assay. RESULTS: TREM-1 expression by resident
      peritoneal macrophages was significantly induced after stimulation with the
      crystals. Maximum expression of TREM-1 transcripts and protein occurred at 1 and
      4 hours after exposure to the crystals, respectively. Costimulation of resident
      peritoneal macrophages with MSU crystals and an anti-TREM-1 agonist antibody
      synergistically increased the production of both interleukin-1beta and monocyte
      chemotactic protein 1 compared with stimulation with the crystals alone. MSU
      crystals also induced TREM-1 expression in infiltrating leukocytes in a murine
      air-pouch model of crystal-induced acute inflammation. CONCLUSION: These findings
      suggest that rapid induction of TREM-1 expression on resident peritoneal
      macrophages and neutrophils by MSU crystals may contribute to the development of
      acute gout through enhancement of inflammatory responses.

PMID- 16447219
TI  - The accumulation of intracellular ITEGE and DIPEN neoepitopes in bovine articular
      chondrocytes is mediated by CD44 internalization of hyaluronan.
AB  - OBJECTIVE: A dramatic loss of aggrecan proteoglycan from cartilage is associated
      with osteoarthritis. The fate of residual G1 domains of aggrecan is unknown, but
      inefficient turnover of these domains may impede subsequent repair and retention
      of newly synthesized aggrecan. Thus, the objective of this study was to determine
      whether ITEGE- and DIPEN-containing G1 domains, generated in situ, are
      internalized by articular chondrocytes, and whether these events are dependent on
      hyaluronan (HA) and its receptor, CD44. METHODS: ITEGE and DIPEN neoepitopes were
      detected by immunofluorescence staining of bovine articular cartilage
      chondrocytes treated with or without interleukin-1alpha (IL-1alpha).
      Additionally, purified ITEGE- or DIPEN-containing G1 domains were aggregated with
      HA and then added to articular chondrocytes, articular chondrocytes transfected
      with CD44delta67, or COS-7 cells transfected with or without full-length CD44.
      Internalized epitopes were distinguished by their resistance to extensive
      trypsinization of the cell surface. RESULTS: Both ITEGE and DIPEN were visualized
      within the extracellular cell-associated matrix of chondrocytes as well as within
      intracellular vesicles. Following trypsinization, the intracellular accumulation
      of both epitopes was clearly visible. IL-1 treatment increased extracellular as
      well as intracellular ITEGE epitope accumulation. Once internalized, the ITEGE
      neoepitope became localized within the nucleus and displayed little
      colocalization with HA, DIPEN, or other G1 domain epitopes. The internalization
      of both ITEGE and DIPEN G1 domains was dependent on the presence of HA and CD44.
      CONCLUSION: One important mechanism for the elimination of residual G1 domains
      following extracellular degradation of aggrecan is CD44-mediated co
      internalization with HA.

PMID- 16447221
TI  - Activation of p38 MAPK is a key step in tumor necrosis factor-mediated
      inflammatory bone destruction.
AB  - OBJECTIVE: To investigate whether activation of p38 MAPK is a crucial signaling
      factor in inflammatory bone destruction mediated by tumor necrosis factor (TNF).
      Mice overexpressing TNF were treated with 2 different inhibitors of p38 MAPK, and
      the effect of this treatment on joint inflammation and structural damage was
      assessed. METHODS: Human TNF-transgenic mice received systemic treatment with 2
      different p38 MAPK inhibitors (RO4399247 and AVE8677). Treatment was started at
      the time of symptom onset and lasted for 6 weeks. Mice were assessed for clinical
      signs of arthritis, bone erosion, and cartilage damage. In addition, the effect
      of these inhibitors on osteoclast generation in vitro and in vivo was assessed.
      RESULTS: Both p38 MAPK inhibitors significantly reduced clinical signs of TNF
      mediated arthritis. This was attributable to reducing synovial inflammation by
      50% without affecting the cellular composition of the infiltrate. Synovial
      expression of interleukin-1 and RANKL was reduced upon p38 MAPK blockade, and
      activation of the molecular target MAPK-activated protein kinase 2 (MAPKAP-2) was
      also inhibited. Proteoglycan loss of articular cartilage was reduced by 50%,
      although p38 MAPK inhibition did not change matrix molecule synthesis by
      cultivated chondrocytes. Importantly, bone loss was almost completely prevented
      by p38 MAPK inhibition. The numbers of synovial osteoclasts and precursors were
      dramatically reduced, and both p38 MAPK inhibitors also inhibited in vitro
      osteoclastogenesis at micromolar concentrations and blocked activation of MAPKAP
      2 as well as differentiation markers in cultured osteoclast precursors.
      CONCLUSION: These results suggest the major importance of p38 MAPK for TNF
      mediated inflammatory bone destruction in arthritis and suggest that inhibition
      of p38 MAPK might be an important tool for reducing structural damage in
      rheumatoid arthritis.

PMID- 16447222
TI  - The impact of glycosylation on HLA-DR1-restricted T cell recognition of type II
      collagen in a mouse model.
AB  - OBJECTIVE: Type II collagen (CII) is a candidate autoantigen implicated in the
      pathogenesis of rheumatoid arthritis (RA). Posttranslational glycosylation of CII
      could alter intracellular antigen processing, leading to the development of
      autoimmune T cell responses. To address this possibility, we studied the
      intracellular processing of CII for presentation of the arthritogenic
      glycosylated epitope CII(259-273) to CD4 T cells in macrophages from HLA-DR1
      transgenic mice. METHODS: HLA-DR1-transgenic mice were generated on a class II
      major histocompatibility complex-deficient background, and T cell hybridomas
      specific for the glycosylated and nonglycosylated epitope CII(259-273) were
      developed. Subcellular fractionation of macrophages was used to localize CII
      degradation to particular compartments and to identify the catalytic subtype of
      proteinases involved. RESULTS: We showed that the glycosylated CII(259-273)
      epitope required more extensive processing than did the nonglycosylated form of
      the same epitope. Dense fractions containing lysosomes were primarily engaged in
      the processing of CII for antigen presentation, since these compartments
      contained 1) enzyme activity that generated antigenic CII fragments bearing the
      arthritogenic glycosylated epitope, 2) the antigenic CII fragments themselves, 3)
      CII peptide-receptive HLA-DR1 molecules, and 4) peptide/HLA-DR1 complexes that
      could directly activate T cell hybridomas. Degradation of CII by dense fractions
      occurred optimally at pH 4.5 and was abrogated by inhibitors of serine and
      cysteine proteinases. CONCLUSION: Processing of the arthritogenic glycosylated
      CII(259-273) epitope, which is implicated in the induction of autoimmune
      arthritis, is more stringently regulated than is processing of the
      nonglycosylated form of the same epitope. Mechanisms of intracellular processing
      of the glycosylated epitope may constitute novel therapeutic targets for the
      treatment of RA.

PMID- 16447223
TI  - Prevention of spontaneous arthritis by inhibiting homeostatic expansion of
      autoreactive CD4+ T cells in the K/BxN mouse model.
AB  - OBJECTIVE: K/BxN-transgenic mice are a model of autoimmune arthritis, similar to
      rheumatoid arthritis. This study was undertaken to determine whether inhibition
      of lymphopenia-provoked homeostatic expansion can prevent spontaneous development
      of disease in the K/BxN model. METHODS: To inhibit homeostatic expansion of
      autoreactive T cells, K/BxN mice with disease in the preclinical stage were
      adoptively transferred with CD4+ T cells purified from nontransgenic BxN or
      Thy1.1+ BxN mice. To observe the profile of proliferation of CD4+ T cells derived
      from the hosts, carboxyfluorescein diacetate succinimidyl ester-labeled
      autologous CD4+ T cells were cotransferred to K/BxN mice together with BxN CD4+ T
      cells. Disease onset and progression were scored, and the dynamics and phenotypes
      of recipient CD4+ T cells were determined by flow cytometry, before and after
      cell infusion. RESULTS: During the preclinical phase of disease, K/BxN mice
      exhibited CD4+ T lymphopenia, which was followed by a compensatory expansion of
      these cells during the early clinical phase. The majority of CD4+ T cells
      acquired a memory phenotype (CD44(high),CD62L(low),CD25-), which is a hallmark of
      homeostatically expanding cells. Importantly, K/BxN mice subjected to syngeneic T
      cell transfer did not develop symptoms of arthritis and also possessed fewer
      transgenic T cell receptor-encoded Vbeta6+,CD4+ T cells. This effect was
      associated with decreased proliferation of recipient-derived CD4+ T cells but not
      with the function of CD25+ T regulatory cells present in donor cells. CONCLUSION:
      These results provide the first evidence that lymphopenia-associated homeostatic
      proliferation of autoreactive CD4+ T cells potentiates autoimmune arthritis, and
      that inhibition of this process protects mice from the development of this
      pathologic condition.

PMID- 16447224
TI  - Early cytokine profiles in the joint define pathogen clearance and severity of
      arthritis in Chlamydia-induced arthritis in rats.
AB  - OBJECTIVE: Although Chlamydia trachomatis-induced arthritis is among the most
      common rheumatic diseases having an identified infectious trigger, the
      pathogenesis of this arthritis is not well defined. We sought to investigate the
      host-microbe interactions that contribute to the severity of arthritis initiated
      by chlamydial infection. METHODS: We established an experimental rat model of C.
      trachomatis-induced arthritis that recapitulates many pathologic features of the
      clinical disease. The severity of the arthritis was defined using an established
      histopathologic scoring system. Host clearance of the pathogen and local cytokine
      production were examined by enzyme-linked immunosorbent assays. RESULTS: Lewis
      rats were susceptible to C. trachomatis-induced arthritis, whereas BN rats were
      relatively resistant to this disease. Significant differences in the
      histopathologic severity of arthritis were originally observed on day 21, and
      this prompted an examination of the acute phase of the arthritis. As early as day
      5 after the onset of the arthritis, pathologic changes in Lewis rats were more
      severe than those in BN rats. An evaluation of the role of complement using cobra
      venom factor treatment excluded complement as being the key to differential
      sensitivity, because decomplementation did not eliminate the differences in
      arthritis severity between Lewis and BN rats. Host clearance, in contrast, was
      significantly different between the rat strains, with BN rats showing more prompt
      and effective clearance of the pathogen from both synovial tissues and spleen
      compared with Lewis rats. Local cytokine profiles demonstrated that host
      resistance was characterized by enhanced synovial expression of tumor necrosis
      factor alpha, interferon-gamma (IFNgamma), and interleukin-4. CONCLUSION: These
      studies demonstrated that cytokines thought to be proinflammatory in nature can
      play an important role in host defense in infection-triggered arthritis and serve
      to highlight the dynamic cytokine relationships that constitute effective host
      pathogen interactions.

PMID- 16447225
TI  - PYPAF1 nonsense mutation in a patient with an unusual autoinflammatory syndrome:
      role of PYPAF1 in inflammation.
AB  - OBJECTIVE: To gain insight into the pathophysiology of an unusual
      autoinflammatory syndrome, in a patient of Armenian origin, that mimicked
      familial Mediterranean fever (FMF) but with episodes triggered by generalized
      exposure to cold, and to further elucidate the controversial function of the
      protein encoded by PYPAF1, whose mutations (exclusively missense to date) have
      been identified in 3 hereditary recurrent fever syndromes. METHODS: The patient's
      DNA was screened for mutations in both MEFV, the gene responsible for FMF, and
      PYPAF1. The ability of different recombinant PYPAF1 isoforms, expressed in HEK
      293 cells, to regulate NF-kappaB signaling was subsequently assessed. RESULTS: No
      disease-causing mutation was found in MEFV. However, a nonsense mutation
      (p.Arg554X) was identified in PYPAF1; this defect resulted in a truncated protein
      lacking all leucine-rich repeats. Study of the wild-type and mutant PYPAF1
      recombinant proteins revealed that PYPAF1 inhibited NF-kappaB proinflammatory
      pathways, and that the identified nonsense mutation impaired this property.
      CONCLUSION: These molecular and clinical findings, together with the clinical
      manifestations in the patient, which call into question the current nosology of
      the hereditary recurrent fever syndromes, are consistent with the hypothesis that
      PYPAF1 acts as an inhibitor of NF-kappaB signaling. They also provide a clear
      elucidation of the functional consequences of this nonsense PYPAF1 mutation not
      previously described in the literature, which result in a partial loss of
      function and may thereby explain the pathophysiology of the autoinflammatory
      syndrome observed in this patient.

PMID- 16447226
TI  - Clinical study of hereditary disorders of connective tissues in a Chilean
      population: joint hypermobility syndrome and vascular Ehlers-Danlos syndrome.
AB  - OBJECTIVE: To demonstrate the high frequency and lack of diagnosis of joint
      hypermobility syndrome (JHS) and the seriousness of vascular Ehlers-Danlos
      syndrome (VEDS). METHODS: Two hundred forty-nine Chilean patients with hereditary
      disorders of the connective tissues (CTDs) and 64 control subjects were evaluated
      for the diagnoses of JHS and VEDS using the validated Brighton criteria, as
      compared with the traditional Beighton score. In addition, the presence of blue
      sclera was determined, with the degree of intensity graded as mild, moderate, or
      marked. RESULTS: The frequency of hereditary CTDs was 35%, with diagnoses of JHS
      in 92.4% of subjects, VEDS in 7.2%, and osteogenesis imperfecta in 0.4%. The
      Beighton score proved to be insufficient for the diagnosis of JHS (35% of
      subjects had a negative score), whereas the Brighton criteria yielded positive
      findings (a diagnosis of JHS) in 39% of control subjects. Blue sclera was
      frequent, being identified in 97% of JHS patients and 94% of VEDS patients.
      Moderate osteopenia/osteoporosis was observed in 50% of patients with VEDS and
      26% of those with JHS. Dysautonomia, dyslipidemia, and scoliosis were more
      frequent in VEDS patients than in JHS patients. The typical JHS facial appearance
      and the "hand holding the head sign" were identified. Raynaud's phenomenon was
      extremely rare in JHS patients (2%). Ruptured uterus and cerebral aneurysm
      occurred in 12% and 6% of VEDS patients, respectively. Spontaneous pneumothorax
      was more frequent in VEDS patients (11%) than in JHS patients (0.9%). CONCLUSION:
      JHS is very frequent but usually undiagnosed. The Beighton score is an
      insufficient method for JHS diagnosis. We recommend that physicians learn to
      recognize the typical facial features of JHS and be able to identify blue sclera.
      We also propose that validated hypermobility criteria be routinely used. Further
      research is needed to determine why the prevalence of JHS is so high in Chile.

PMID- 16447227
TI  - Signaling pathways regulating intercellular adhesion molecule 1 expression by
      endothelin 1: comparison with interleukin-1beta in normal and scleroderma dermal
      fibroblasts.
AB  - OBJECTIVE: Endothelin 1 (ET-1) has been implicated in the pathogenesis of
      fibrotic and inflammatory diseases, including scleroderma. In addition to
      modulating vascular tone and extracellular matrix turnover, ET-1 up-regulates
      cell surface adhesion molecules including intercellular adhesion molecule 1 (ICAM
      1), which is key to cell-cell and cell-matrix adhesion and leukocyte
      infiltration. This study was undertaken to delineate the signal transduction
      pathways utilized by ET-1 and compare them with those adopted by proinflammatory
      cytokine interleukin-1beta (IL-1beta) in normal and scleroderma dermal
      fibroblasts. METHODS: Protein expression induced by ET-1 and IL-1beta on normal
      dermal fibroblasts, with or without signaling inhibitors, was detected by enzyme
      linked immunosorbent assay, while messenger RNA (mRNA) levels were analyzed by
      LightCycler polymerase chain reaction. Expression of protein kinase Cdelta
      (PKCdelta) and PKCepsilon protein in normal dermal fibroblasts and scleroderma
      dermal fibroblasts was determined by Western blotting, and PKCepsilon involvement
      in ET-1 signaling was confirmed through transfection of an ICAM-1 promoter
      construct into murine PKCepsilon-/- fibroblasts. NF-kappaB activation was
      confirmed via electrophoretic mobility supershift assay, and analysis of the ICAM
      1 promoter region was achieved via transfection of deletion constructs into human
      dermal fibroblasts. RESULTS: In normal dermal fibroblasts, ET-1 induced ICAM-1
      mRNA and surface protein expression in a dose- and time-dependent manner via both
      receptor subtypes, ET(A) and ET(B); antagonism of both abolished the ET-1
      response. MEK was involved in the signaling cascade, but phosphatidylinositol 3
      kinase and p38 MAPK were not. Key to the cascade was activation of NF-kappaB,
      achieved by ligation of either receptor subtype. PKCepsilon activation led to
      downstream activation of MEK and, in part, NF-kappaB. IL-1beta signaling required
      NF-kappaB and MEK activation, along with activation of PKCdelta. ET-1 and IL
      1beta each utilized the same ICAM-1 promoter region and the same NF-kappaB site
      at -157 bp. Responses to ET-1 and IL-1beta differed in scleroderma dermal
      fibroblasts, with ET-1 sensitivity decreasing and IL-1beta responses remaining
      intact. Expression of PKCepsilon and PKCdelta in scleroderma dermal fibroblasts
      was also altered. CONCLUSION: The findings of this study indicate that
      differences in sensitivity to ET-1 and IL-1beta in scleroderma dermal fibroblasts
      may be explained by altered expression of the PKC isoforms and cytokine
      receptors.

PMID- 16447228
TI  - Hepatology citation.

PMID- 16447229
TI  - Association between a variation in LRCH1 and knee osteoarthritis: a genome-wide
      single-nucleotide polymorphism association study using DNA pooling.
AB  - OBJECTIVE: To perform a large-scale association analysis of single-nucleotide
      polymorphisms (SNPs) in patients with radiographically defined osteoarthritis
      (OA) of the knee. METHODS: We examined >25,000 SNPs located within approximately
      14,000 genes for associations with radiographically defined knee OA, using
      polymerase chain reaction and MassExtend amplification techniques. Allele
      frequencies were estimated initially in DNA pools from 335 female patients with
      knee OA and 335 asymptomatic and radiographically negative female control
      subjects. All were of northern European ancestry. Significant allele frequency
      differences were validated by genotyping of individual DNA samples. Confirmed
      significant findings were verified in 2 additional case-control samples from the
      UK (443 cases and 303 controls) and Newfoundland (346 cases and 264 controls).
      Chondrosarcoma cell lines were used to test for potential differences in gene
      expression. RESULTS: The marker most strongly associated with the risk of knee OA
      was rs912428, a C/T polymorphism in intron 1 of LRCH1, a gene on chromosome 13q14
      that encodes a novel protein of as-yet-unknown function. The frequency of the T
      allele compared with controls was consistently increased by 40% across all 3 case
      control groups. Additional subanalyses in case-control samples with hip OA and
      hand OA suggested similar trends, but did not reach statistical significance.
      Association fine-mapping using 10 additional SNPs in LRCH1 confirmed intron 1 as
      the region of highest association but failed to reveal variations with
      significance stronger than the marker SNP, as did the haplotype analysis. LRCH1
      was not up-regulated or overexpressed in chondrosarcoma cell lines exposed to
      inflammatory stimuli, suggesting a possible structural role. CONCLUSION: A
      genetic variant in LRCH1 was consistently associated with knee OA in 3 samples
      from 2 populations. Our results also suggest that the same association with OA
      may exist at other sites. Additional genetic and experimental work is needed to
      elucidate the precise mechanism by which the LRCH1 gene influences OA risk.

PMID- 16447230
TI  - Interleukin-1 in combination with oncostatin M up-regulates multiple genes in
      chondrocytes: implications for cartilage destruction and repair.
AB  - OBJECTIVE: To identify the genes up-regulated by interleukin-1 (IL-1) in
      combination with oncostatin M (OSM) in chondrocytes that may be involved in
      mechanisms of cartilage repair and degradation. METHODS: Gene microarray and real
      time polymerase chain reaction (PCR) experiments were performed using RNA from
      SW1353 chondrocytes and primary human articular chondrocytes. Sections prepared
      from murine joints, injected with adenovirus vectors overexpressing IL-1 and/or
      OSM, were analyzed by immunohistochemistry for selected proteins. RESULTS: The
      combination of IL-1 and OSM markedly up-regulated the expression of various
      genes, including matrix metalloproteinases (MMPs), cytokines, chemokines,
      extracellular matrix components, and genes involved in signal transduction. Real
      time PCR confirmed a synergistic induction of several MMPs, activin A, pentraxin
      3 (PTX-3), and IL-8. The in vivo findings further indicated that stimulation with
      IL-1 plus OSM induced protein expression of activin A, PTX-3, and KC (the murine
      homolog of IL-8), as compared with the changes induced by individual cytokine
      treatment and unstimulated controls. CONCLUSION: The results confirm that the
      potent proinflammatory cytokine combination of IL-1 plus OSM synergistically and
      coordinately up-regulates many genes and several MMPs. Moreover, chondrocytes
      exhibit a potential repair response following this procatabolic stimulus such
      that the repair mechanisms are ultimately overwhelmed by degradative processes in
      the cartilage. This gene-profiling study provides insight into the complex
      processes that mediate joint disease in the inflammatory arthritides through the
      coordinated expression of multiple genes.

PMID- 16447231
TI  - Validity, factor structure, and clinical relevance of the AUSCAN Osteoarthritis
      Hand Index.
AB  - OBJECTIVE: The Australian/Canadian (AUSCAN) Osteoarthritis Hand Index is a self
      report assessment of pain, stiffness, and function in patients with hand
      osteoarthritis (OA). Small studies have confirmed the reliability, construct
      validity, and responsiveness of this measure, but the factor structure has not
      been examined. In this study, we examined the clinimetric properties and clinical
      relevance of the AUSCAN index in a large sample of patients with familial hand
      OA. METHODS: The study group comprised 700 patients (80% female, mean age 69
      years) who were part of a study on the genetics of generalized OA. All patients
      had radiographic hand OA bilaterally. The analyses examined internal consistency,
      factor structure, and relationships of the subscales to grip and pinch strength
      and a single-item pain measure. RESULTS: Internal consistency was high for the
      total AUSCAN index and the subscales (Cronbach's alpha = 0.93-0.96). The AUSCAN
      function subscale had the strongest correlation with grip and pinch strength, and
      the pain subscale had the strongest correlation with the single-item pain
      measure, thus supporting the construct validity of these subscales. Factor
      analysis showed that all pain and function items clearly loaded on the subscale
      they were intended to measure. Each 1-unit increase in the AUSCAN function
      subscale was associated with a clinically relevant decrease in hand strength.
      CONCLUSION: The results of this study strongly confirm the clinimetric properties
      of the AUSCAN index, including the validity of specific subscales. Results
      indicate that the AUSCAN index can measure meaningful changes in pain, stiffness,
      and function.

PMID- 16447232
TI  - Acquired resistance to chloroquine in human CEM T cells is mediated by multidrug
      resistance-associated protein 1 and provokes high levels of cross-resistance to
      glucocorticoids.
AB  - OBJECTIVE: To explore the onset and molecular mechanism of resistance to the
      antimalarial disease-modifying antirheumatic drug (DMARD) chloroquine (CQ) in
      human CEM T cells. METHODS: Human CEM cells were used as an in vitro model system
      to study the development of CQ resistance by growing cells in stepwise increasing
      concentrations of CQ. RESULTS: Over a period of 6 months, CEM cell lines
      developed 4-5-fold resistance to CQ. CQ resistance was associated with the
      specific overexpression of multidrug resistance-associated protein 1 (MRP-1), an
      ATP-driven drug efflux pump. This was illustrated by 1) overexpression of MRP-1
      by Western blotting and 2) the complete reversal of CQ resistance by the MRP-1
      transport inhibitors MK571 and probenecid. Importantly, CQ-resistant CEM cells
      retained full sensitivity to other DMARDs, including methotrexate, leflunomide,
      cyclosporin A, and sulfasalazine, but exhibited a high level of cross-resistance
      (>1,000-fold) to the glucocorticoid dexamethasone. The mechanistic basis for the
      latter was associated with aberrant signaling via the cAMP-protein kinase A
      pathway, since the cAMP-inducing agent forskolin reversed dexamethasone
      resistance. Finally, CQ-resistant CEM cells displayed a markedly reduced capacity
      to release proinflammatory cytokines (tumor necrosis factor alpha) and chemokines
      (interleukin-8). CONCLUSION: Induction of overexpression of the multidrug
      resistance efflux transporter MRP-1 can emerge after long-term exposure to CQ and
      results in CQ resistance and collateral resistance to dexamethasone. These
      findings warrant further detailed investigations into the possible role of MRP-1
      and other members of the superfamily of drug efflux pumps in diminishing the
      efficacy of DMARDs in rheumatoid arthritis treatment.

PMID- 16447233
TI  - Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical
      history for application as classification and diagnostic criteria.
AB  - OBJECTIVE: Back pain associated with ankylosing spondylitis (AS) is referred to
      as inflammatory back pain (IBP). The value of the clinical history in
      differentiating IBP from mechanical low back pain (MLBP) has been investigated in
      only a few studies. In this exploratory study, we sought to evaluate the
      individual features of IBP and to compose and compare various combinations of
      features for use as classification and diagnostic criteria. METHODS: We assessed
      the clinical history of 213 patients (101 with AS and 112 with MLBP) younger than
      50 years who had chronic back pain. Single clinical parameters and combinations
      of parameters were compared between the AS and MLBP patient groups. RESULTS:
      Morning stiffness of >30 minutes' duration, age at onset of back pain, no
      improvement in back pain with rest, awakening because of back pain during the
      second half of the night only, alternating buttock pain, and time period of the
      onset of back pain were identified as independent contributors to IBP.
      Importantly, none of the single parameters sufficiently differentiated AS from
      MLBP. In contrast, several sets of combined parameters proved to be well balanced
      between sensitivity and specificity. Among these, a new candidate set of criteria
      for IBP, which consisted of morning stiffness of >30 minutes' duration,
      improvement in back pain with exercise but not with rest, awakening because of
      back pain during the second half of the night only, and alternating buttock pain,
      yielded a sensitivity of 70.3% and a specificity of 81.2% if at least 2 of these
      4 parameters were fulfilled (positive likelihood ratio 3.7). If at least 3 of the
      4 parameters were fulfilled, the positive likelihood ratio increased to 12.4.
      CONCLUSION: A new set of criteria for IBP performed better than previous criteria
      in AS patients with established disease. A prospective study is needed to
      validate the diagnostic properties of the new candidate criteria set in patients
      with early disease.

PMID- 16447234
TI  - Apoptosis of rheumatoid synovial cells by statins through the blocking of protein
      geranylgeranylation: a potential therapeutic approach to rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether statins induce apoptosis in rheumatoid arthritis
      (RA) synoviocytes. METHODS: The effects of lipophilic and hydrophilic statins
      (fluvastatin and pravastatin, respectively) on the apoptosis of cultured RA
      synoviocytes were examined in vitro. Apoptosis was analyzed by flow cytometry
      after staining with JC-1 (to measure the mitochondrial transmembrane potential),
      active caspase 3, annexin V, and propidium iodide. Add-back experiments were
      conducted to determine which downstream products of the mevalonate pathway could
      suppress apoptosis. Modulation of various signaling pathways induced by statins,
      including protein prenylation, was also investigated. RESULTS: Fluvastatin, but
      not pravastatin, induced apoptosis in RA synoviocytes in a concentration
      dependent (1-10 microM) and time-dependent (48-96 hours) manner. Another
      lipophilic statin, pitavastatin, displayed almost the same effects as
      fluvastatin. In sharp contrast, lipophilic statins did not significantly increase
      apoptosis in synoviocytes from patients with osteoarthropathy. Apoptosis induced
      by fluvastatin was mitochondrial- and caspase 3-dependent and was abrogated by
      mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate.
      In addition, the geranylgeranyl transferase inhibitor GGTI-298 mimicked the
      effect of fluvastatin on RA synoviocytes. Treatment of RA synoviocytes with the
      RhoA kinase inhibitor Y-27632 caused apoptosis. Fluvastatin decreased the amount
      of RhoA protein in the membrane fraction, but increased the amount in the
      cytosolic fraction. CONCLUSION: Fluvastatin induced apoptosis in RA synoviocytes
      through a mitochondrial- and caspase 3-dependent pathway and by the blockage of
      mevalonate pathways, particularly through the inhibition of protein
      geranylgeranylation and RhoA/RhoA kinase pathways. These findings suggest that
      lipophilic statins have potential as novel therapeutic agents for RA.

PMID- 16447235
TI  - PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes.
AB  - OBJECTIVE: Although p53 is overexpressed in rheumatoid arthritis (RA) synovial
      tissue (ST), few synoviocytes undergo apoptosis. This could be partly due to low
      expression of proapoptotic genes. Deficient p53 up-regulated modulator of
      apoptosis (PUMA), which is a major effector of p53-mediated cell death, could
      contribute to this phenomenon. To evaluate a method to induce apoptosis, the
      expression and function of PUMA was investigated in ST and cultured fibroblast
      like synoviocytes (FLS). METHODS: PUMA expression in ST was measured by
      immunohistochemistry, Western blot analysis, and quantitative polymerase chain
      reaction analysis. Ad-p53 and plasmids encoding hemagglutinin-tagged, full-length
      PUMA expression vector (HA-PUMA), PUMA lacking the Bcl-2 homology 3 domain, or
      pCEP4 were used to transfect FLS. Apoptosis was quantified by trypan blue
      exclusion, DNA fragmentation, and caspase 3 activation. RESULTS: PUMA protein was
      detected in RA ST, although most of the immunoreactive protein was localized to
      sublining cells rather than the intimal lining synoviocytes. Western blot
      analysis showed no difference between RA ST and osteoarthritis (OA) ST. PUMA
      messenger RNA was detected in RA and OA ST, although the amounts were markedly
      lower than in the spleen and FLS. To determine if PUMA was inducible, FLS were
      transduced with Ad-p53. Even though p53 protein was produced and p21 expression
      was increased, PUMA expression was not enhanced. Consistent with this
      observation, Ad-p53 did not induce apoptosis in FLS. However, HA-PUMA
      transfection into FLS resulted in rapid apoptosis with the activation of caspase
      3. CONCLUSION: PUMA can induce apoptosis by FLS and represents a potential target
      in RA.

PMID- 16447236
TI  - A new classification of HLA-DRB1 alleles differentiates predisposing and
      protective alleles for rheumatoid arthritis structural severity.
AB  - OBJECTIVE: A new classification of HLA-DRB1 alleles supporting the shared epitope
      hypothesis of rheumatoid arthritis (RA) susceptibility was recently introduced.
      We investigated the relevance of this classification in terms of the structural
      severity of RA. METHODS: The study group comprised 144 patients who were included
      in a prospective longitudinal cohort of French Caucasoid patients with early RA.
      Progression of the total radiographic damage score (Sharp/van der Heijde method)
      was used to quantify the structural severity of RA after 4 years of followup. HLA
      DRB1 typing and subtyping were performed by polymerase chain reaction, using a
      panel of sequence-specific oligonucleotide probes. HLA-DRB1 alleles were
      classified according to the above-mentioned new system. The association between
      the HLA-DRB1 allele groups (S1, S2, S3P, S3D, and X) and the structural severity
      of RA was analyzed with nonparametric statistical tests. RESULTS: The presence of
      S2 alleles (HLA-DRB1*0401 and HLA-DRB1*1303) was associated with severe forms of
      RA (P = 0.004); a significant dose effect was observed (P = 0.01). The presence
      of S3D alleles (HLA-DRB1*11001, HLA-DRB1*1104, HLA-DRB1*12, and HLA-DRB1*16) was
      associated with benign forms of RA (P < 0.0001), and a significant dose effect
      was observed (P < 0.01). CONCLUSION: The studied classification of HLA-DRB1
      alleles is relevant in terms of RA outcomes. Compared with a previously described
      classification system, this system differentiates predisposing (S2) and
      protective (S3D) alleles for RA structural severity, which, respectively,
      correspond to KRRAA and DRRAA amino acid patterns at position 70-74 of the third
      hypervariable region of the HLA-DRbeta chain.

PMID- 16447237
TI  - The LUNDEX, a new index of drug efficacy in clinical practice: results of a five
      year observational study of treatment with infliximab and etanercept among
      rheumatoid arthritis patients in southern Sweden.
AB  - OBJECTIVE: To describe the use of the LUNDEX, a new index for comparing the long
      term efficacy and tolerability of biologic therapies in rheumatoid arthritis (RA)
      patients treated in clinical practice. METHODS: Patients (n = 949) with active RA
      that had not responded to at least 2 disease-modifying antirheumatic drugs
      (DMARDs) including methotrexate, in whom biologic therapy was being initiated,
      were included in a structured clinical followup protocol. The protocol included
      collection of data on diagnosis, disease duration, previous and ongoing DMARD
      treatment, and dates on which biologic treatment was started and terminated. In
      addition, data on efficacy measures used for calculating validated response
      criteria, i.e., the European League Against Rheumatism and American College of
      Rheumatology response criteria, were collected at fixed time points. Data were
      prospectively registered from March 1999 through January 2004. The LUNDEX, a new
      index combining the proportion of patients fulfilling a selected response
      criteria set with the proportion of patients adhering to a particular therapy,
      was designed to compare the efficacy of the different therapies. RESULTS:
      Etanercept had higher overall LUNDEX values compared with infliximab, mostly
      because of a lower rate of adherence to therapy with infliximab. The relationship
      between the drugs was consistent irrespective of the response criteria used.
      CONCLUSION: The LUNDEX is a valuable tool for evaluating drug efficacy in
      observational studies. It has the advantage of integrating clinical response as
      well as adherence to therapy in a composite value. Moreover, the LUNDEX has a
      practical and potentially universal application independent of diagnosis and
      response criteria.

PMID- 16447238
TI  - Risk genotypes in folate-dependent enzymes and their association with
      methotrexate-related side effects in rheumatoid arthritis.
AB  - OBJECTIVE: Methotrexate (MTX) is an antifolate agent that is often associated
      with toxicity. This study investigated whether risk genotypes for folate
      dependent enzymes are associated with the toxicity of MTX in patients with
      rheumatoid arthritis (RA). METHODS: Blood was collected for analysis in a
      muticenter, cross-sectional study of RA patients who had been receiving MTX for
      at least 1 month prior to enrollment, and side effects occurring at the time of a
      single study visit were recorded. Low-penetrance risk genotypes in
      methylenetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER)
      *2/*2 (variable number of tandem repeats), amino imidazole ribonucleotide
      transformylase (ATIC) 347GG, and serine hydroxymethyltransferase (SHMT1) 1420CC
      were measured and summed to constitute the toxicogenetic index specific to each
      patient. Statistical analyses consisted of logistic regression models with
      clustered-center effects, and associations with risk genotypes were expressed as
      adjusted odds ratios (ORs). RESULTS: Among 214 patients enrolled at 4 study
      sites, a total of 67 patients (31%) presented with a side effect
      (gastrointestinal event, headache, lethargy, alopecia, cough, or dyspnea). Risk
      genotypes associated with side effects in the central nervous system were MTHFR
      677TT (OR 3.3, P < 0.01) and SHMT1 1420CC (OR 2.4, P < 0.05). ATIC 347GG was
      associated with gastrointestinal side effects (OR 3.0, P < 0.01), while TSER*2/*2
      (OR 5.4, P < 0.01) and SHMT1 1420CC (OR 3.2, P < 0.01) were associated with
      alopecia. The toxicogenetic index ranged from 0 to 3 (median 1). An index of 3
      was associated with an approximately 7-fold higher likelihood of having a side
      effect compared with an index of 0 (P < 0.01). CONCLUSION: These data suggest
      that a composite index of the cumulative risk genotypes in folate-dependent
      enzymes may be an effective means of profiling RA patients who develop side
      effects to MTX.

PMID- 16447239
TI  - Reconstitution of peripheral blood B cells after depletion with rituximab in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: To study the quantitative and phenotypic reconstitution of peripheral
      blood B cells and its relationship to the dynamics of clinical response in
      patients with rheumatoid arthritis (RA) following B cell depletion with
      rituximab. METHODS: Twenty-four patients with active RA treated with rituximab
      were studied. Flow cytometry with combinations of monoclonal antibodies to B cell
      and T cell subsets was used. RESULTS: The frequency and total number of CD19+
      cells in the peripheral blood decreased a mean of 97% for more than 3 months in
      all but 1 patient following rituximab therapy. All B cell populations were
      depleted. More than 80% of residual B cells showed a memory or plasma cell
      precursor phenotype. B cell repopulation occurred a mean of 8 months after
      treatment and was dependent on the formation of naive B cells, which showed an
      increased expression of CD38 and CD5. During repopulation, increased numbers of
      circulating immature B cells, CD19+,IgD+,CD38(high),CD10(low),CD24(high) cells,
      were identified. Patients who experienced a relapse of RA on return of B cells
      tended to show repopulation with higher numbers of memory B cells. A small number
      of T cells and natural killer cells expressed low levels of CD20. These cells
      were depleted following rituximab therapy and returned to the circulation a mean
      of 5 months after treatment. No other significant changes were detected in the T
      cell populations studied. CONCLUSION: Rituximab induced a profound depletion of
      all peripheral blood B cell populations in patients with RA. Repopulation
      occurred mainly with naive mature and immature B cells. Patients whose RA
      relapsed on return of B cells tended to show repopulation with higher numbers of
      memory B cells.

PMID- 16447240
TI  - Treatment of early seropositive rheumatoid arthritis: doxycycline plus
      methotrexate versus methotrexate alone.
AB  - OBJECTIVE: To compare the efficacy of doxycycline plus methotrexate (MTX) versus
      MTX alone in the treatment of early seropositive rheumatoid arthritis (RA), and
      to attempt to differentiate the antibacterial and antimetalloproteinase effects
      of doxycycline. METHODS: Sixty-six patients with seropositive RA of <1 year's
      duration who had not been previously treated with disease-modifying antirheumatic
      drugs were randomized to receive 100 mg of doxycycline twice daily with MTX (high
      dose doxycycline group), 20 mg of doxycycline twice daily with MTX (low-dose
      doxycycline group), or placebo with MTX (placebo group), in a 2-year double-blind
      study. Treatment was started with an MTX dosage of 7.5 mg/week, which was
      titrated every 3 months until remission was reached (maximum dosage of 17.5
      mg/week). The primary end point was an American College of Rheumatology 50%
      improvement (ACR50) response at 2 years. RESULTS: ACR50 responses were observed
      in 41.6% of patients in the high-dose doxycycline group, 38.9% of those in the
      low-dose doxycycline group, and 12.5% of patients in the placebo group. Results
      of chi-square analysis of the ACR50 response in the high-dose doxycycline group
      versus that in the placebo group were significantly different (P = 0.02). Trend
      analysis revealed that the ACR20 response and the ACR50 response were
      significantly different between groups (P = 0.04 and P = 0.03, respectively). MTX
      doses at 2 years were not different among groups. Four patients in the high-dose
      doxycycline group, 2 patients in the low-dose doxycycline group, and 2 patients
      in the placebo group were withdrawn because of toxic reactions. CONCLUSION: In
      patients with early seropositive RA, initial therapy with MTX plus doxycycline
      was superior (based on an ACR50 response) to treatment with MTX alone. The
      therapeutic responses to low-dose and high-dose doxycycline were similar,
      suggesting that the antimetalloproteinase effects were more important than the
      antibacterial effects. Further studies to evaluate the mechanism of action of
      tetracyclines in RA are indicated.

PMID- 16447241
TI  - Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia:
      associations with prednisone, disease-modifying antirheumatic drugs, and anti
      tumor necrosis factor therapy.
AB  - OBJECTIVE: Pneumonia is a major cause of mortality and morbidity in rheumatoid
      arthritis (RA). This study was undertaken to determine the rate and predictors of
      hospitalization for pneumonia and the extent to which specific RA treatments
      increase pneumonia risk. METHODS: RA patients (n = 16,788) were assessed
      semiannually for 3.5 years. Pneumonia was confirmed by medical records or
      detailed patient interview. Covariates included RA severity measures, diabetes,
      pulmonary disease, and myocardial infarction. Cox proportional hazards regression
      was used to determine the multivariable risk associated with RA treatments.
      RESULTS: After adjustment for covariates, prednisone use increased the risk of
      pneumonia hospitalization (hazard ratio [HR] 1.7 [95% confidence interval 1.5
      2.0]), including a dose-related increase in risk (< or = 5 mg/day HR 1.4 [95%
      confidence interval 1.1-1.6], > 5-10 mg/day HR 2.1 [95% confidence interval 1.7
      2.7], > 10 mg/day HR 2.3 [95% confidence interval 1.6-3.2]). Leflunomide also
      increased the risk (HR 1.2 [95% confidence interval 1.0-1.5]). HRs for etanercept
      (0.8 [95% confidence interval 0.6-110]) and sulfasalazine (0.7 [95% confidence
      interval 0.5-1.0]) did not reflect an increased risk of pneumonia. HRs for
      infliximab, adalimumab, and methotrexate were not significantly different from
      zero. CONCLUSION: There is a dose-related relationship between prednisone use and
      pneumonia risk in RA. No increase in risk was found for anti-tumor necrosis
      factor therapy or methotrexate. These data call into question the belief that low
      dose prednisone is safe. Because corticosteroid use is common in RA, the results
      of this study suggest that prednisone exposure may have important public health
      consequences.

PMID- 16447242
TI  - Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid
      arthritis-associated nonspecific interstitial pneumonia and usual interstitial
      pneumonia.
AB  - OBJECTIVE: B lymphocytes are emerging as important elements in the events leading
      to joint destruction in rheumatoid arthritis (RA). However, B lymphocytes have
      not been studied in rheumatoid arthritis (RA)-associated lung disease. We
      performed a morphologic and quantitative analysis of B lymphocytes and plasma
      cells in RA-associated interstitial pneumonia (IP) in comparison with idiopathic
      IP and normal lungs. METHODS: Open-lung biopsy specimens from patients with RA
      associated IP (n = 18), patients with idiopathic IP (n = 21), and control
      subjects (n = 11) were stained with antibodies to CD20 and CD138. Morphologic
      patterns of stained specimens were characterized and staining was quantified
      using computer-assisted image analysis. RESULTS: In RA-associated IP, marked
      follicular B cell hyperplasia was detected, which was limited almost entirely to
      peribronchiolar lymphoid aggregates. Plasma cells were also present in large
      numbers, but showed a more diffuse tissue infiltration. Quantification of B cells
      demonstrated higher cellularity in RA-associated IP (median 2.0%, interquartile
      range [IQR] 1.0-5.7) as compared with idiopathic IP (0.9%, IQR 0.5-2.1). Control
      specimens showed a significantly smaller number of B cells compared with both
      diseases (0.4%, IQR 0.1-1.3). In RA patients who were smokers and in those who
      were male, the proportion of CD20+ tissue areas further increased to 4.3% (IQR
      1.0-5.8) and 3.9% (IQR 0.7-6.9), respectively. CONCLUSION: We demonstrated a
      significant follicular B cell hyperplasia in RA-associated IP. The differences
      between RA-associated IP and idiopathic IP imply a differential emphasis of B
      cell-mediated mechanisms in the 2 diseases despite radiologic and histologic
      similarities and provide a rationale for studying functional aspects of B cell
      involvement in the pathogenesis of RA-associated IP.

PMID- 16447243
TI  - Platelet C4d is highly specific for systemic lupus erythematosus.
AB  - OBJECTIVE: Complement-activation product C4d is deposited on normal erythrocytes,
      while abnormal levels have been observed on the surface of erythrocytes of
      patients with systemic lupus erythematosus (SLE). This study examines whether C4d
      also deposits on human platelet surfaces, and whether platelet-bound C4d may
      provide a biomarker for SLE. METHODS: We conducted a cross-sectional study of 105
      patients with SLE, 115 patients with other diseases, and 100 healthy controls.
      Levels of C4d on the surface of platelets were examined by flow cytometry and
      scanning confocal microscopy. Statistical analyses were performed to determine
      the clinical variables associated with platelet C4d. RESULTS: Abnormal levels of
      platelet C4d were found to be highly specific for SLE. Platelet C4d was detected
      in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared
      with healthy controls and 98% specific for SLE compared with patients with other
      diseases (P < 0.0001). In addition, platelet C4d was significantly associated
      with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin
      antibodies of the IgG (P = 0.035) or the IgM (P = 0.016) isotype. Platelet C4d
      was also significantly associated with SLE disease activity according to the SLE
      Disease Activity Index (P = 0.039), low serum C4 (P = 0.046), an elevated
      erythrocyte sedimentation rate (P = 0.006), and abnormal levels of C4d on
      erythrocytes (P < 0.0001). CONCLUSION: This observation suggests that platelet
      bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic
      mechanisms responsible for the myriad thrombotic and vascular complications of
      lupus associated with antiphospholipid antibodies.

PMID- 16447244
TI  - ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell
      migration: a comparison between mesothelioma and mesothelial cells.
AB  - Pleural malignant mesothelioma is a locally aggressive tumor of mesothelial cell
      origin. In other tumor types high expression of matrix metalloproteinase (MMP)-2,
      together with membrane-type1-MMP (MT1-MMP), and low levels of the tissue
      inhibitor of MMP (TIMP)-2 have been correlated with aggressive tumor progression
      and low survival rates. Therefore, we compared the expression and activation of
      these three factors and their regulation by two mesothelioma associated growth
      factors, platelet-derived growth factor (PDGF)-BB, and transforming growth factor
      (TGF)-beta1 in six human mesothelioma and one mesothelial cell line. Polymerase
      chain reaction (PCR), immunoblotting, zymography, and small inhibitory RNAs
      (siRNA) were used to study gene expression, protein activation, and signal
      transduction. To proof the relevance of our in vitro data immunohistochemistry
      was performed in tissue sections. PDGF-BB induced, while TGF-beta1 inhibited cell
      proliferation. PDGF-BB was a chemoattractant for mesothelial cells, and its
      effect was increased in the presence of TGF-beta1. TGF-beta1 stimulated the de
      novo synthesis of pro-MMP-2 in both cell types. Pro-MMP-2 synthesis involved p38
      MAP kinase. In cell culture and tissue sections only mesothelial cells expressed
      MT1-MMP. Migration of mesothelioma cells was dependent on the presence of MT1
      MMP. Migration, but not proliferation of mesothelioma cells was inhibited by
      oleoyl-N-hydroxylamide, TIMP-2, and siRNA for MT1-MMP. Our data suggest that in
      mesothelioma cells the phosphorylation of p38 MAP kinase is deregulated and is
      involved in pro-MMP-2 expression. Mesothelioma progression depends on an
      interaction with mesothelial cells that provide MT1-MMP necessary to activate pro
      MMP-2 to facilitate migration through an extracellular matrix (ECM) layer.

PMID- 16447245
TI  - Structural prediction of peptides binding to MHC class I molecules.
AB  - Peptide binding to class I major histocompatibility complex (MHCI) molecules is a
      key step in the immune response and the structural details of this interaction
      are of importance in the design of peptide vaccines. Algorithms based on primary
      sequence have had success in predicting potential antigenic peptides for MHCI,
      but such algorithms have limited accuracy and provide no structural information.
      Here, we present an algorithm, PePSSI (peptide-MHC prediction of structure
      through solvated interfaces), for the prediction of peptide structure when bound
      to the MHCI molecule, HLA-A2. The algorithm combines sampling of peptide backbone
      conformations and flexible movement of MHC side chains and is unique among other
      prediction algorithms in its incorporation of explicit water molecules at the
      peptide-MHC interface. In an initial test of the algorithm, PePSSI was used to
      predict the conformation of eight peptides bound to HLA-A2, for which X-ray data
      are available. Comparison of the predicted and X-ray conformations of these
      peptides gave RMSD values between 1.301 and 2.475 A. Binding conformations of 266
      peptides with known binding affinities for HLA-A2 were then predicted using
      PePSSI. Structural analyses of these peptide-HLA-A2 conformations showed that
      peptide binding affinity is positively correlated with the number of peptide-MHC
      contacts and negatively correlated with the number of interfacial water
      molecules. These results are consistent with the relatively hydrophobic binding
      nature of the HLA-A2 peptide binding interface. In summary, PePSSI is capable of
      rapid and accurate prediction of peptide-MHC binding conformations, which may in
      turn allow estimation of MHCI-peptide binding affinity.

PMID- 16447246
TI  - Association of IgG anti-NR2 glutamate receptor antibodies in cerebrospinal fluid
      with neuropsychiatric systemic lupus erythematosus.

PMID- 16447248
TI  - How psychological stress via hormones and nerve fibers may exacerbate rheumatoid
      arthritis: comment on the review by Straub et al.

PMID- 16447247
TI  - Adalimumab reduces spinal symptoms in active ankylosing spondylitis: clinical and
      magnetic resonance imaging results of a fifty-two-week open-label trial.

PMID- 16447250
TI  - The randomized clinical trial of doxycycline in knee osteoarthritis: comment on
      the editorial by Dieppe.

PMID- 16447251
TI  - Lysyl hydroxylase 3 (LH3) modifies proteins in the extracellular space, a novel
      mechanism for matrix remodeling.
AB  - Lysyl hydroxylase 3 (LH3), the multifunctional enzyme associated with collagen
      biosynthesis that possesses lysyl hydroxylase and collagen glycosyltransferase
      activities, has been characterized in the extracellular space in this study.
      Lysine modifications are known to occur in the endoplasmic reticulum (ER) prior
      to collagen triple-helix formation, but in this study we show that LH3 is also
      present and active in the extracellular space. Studies with in vitro cultured
      cells indicate that LH3, in addition to being an ER resident, is secreted from
      the cells and is found both in the medium and on the cell surface associated with
      collagens or other proteins with collagenous sequences. Furthermore, in vivo, LH3
      is present in serum. LH3 protein levels correlate with the
      galactosylhydroxylysine glucosyltransferase (GGT) activity of mouse tissues.
      This, together with other data, indicates that LH3 is responsible for GGT
      activity in the tissues and that GGT activity assays can be used to quantify LH3
      in tissues. LH3 in vivo is located in two compartments, in the ER and in the
      extracellular space, and the partitioning varies with tissue type. In mouse
      kidney the enzyme is located mainly intracellularly, whereas in mouse liver it is
      located solely in the extracellular space. The extracellular localization and the
      ability of LH3 to modify lysyl residues of extracellular proteins in their
      native, nondenaturated conformation reveals a new dynamic in extracellular matrix
      remodeling, suggesting a novel mechanism for adjusting the amount of
      hydroxylysine and hydroxylysine-linked carbohydrates in collagenous proteins.

PMID- 16447252
TI  - TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and
      progression of pleomorphic adenomas.
AB  - The putative role of TP53 and p16(INK4A) tumor suppressor genes and Ras oncogenes
      in the development and progression of salivary gland neoplasias was studied in 28
      cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case
      of carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were
      analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism
      (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in
      TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in
      H-Ras and K-Ras were identified in 4% (1/28) and 7% (2/28) of PAs, respectively.
      Only 20% (1/5) of carcinomas screened displayed mutations in K-Ras. p16(INK4A)
      promoter hypermethylation was found in 14% (4/28) of PAs and 100% (5/5)
      carcinomas. All genetic and epigenetic alterations were detected exclusively in
      the epithelial and transitional tumor components, and were absent in the
      mesenchymal parts. Our analysis suggests that TP53 mutations and p16(INK4A)
      promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be
      involved in the malignant progression of PA into carcinoma.

PMID- 16447253
TI  - Proteolytic activation of latent TGF-beta precedes caspase-3 activation and
      enhances apoptotic death of lung epithelial cells.
AB  - Transforming growth factors beta (TGF-betas) are multifunctional cytokines, which
      are secreted in latent forms in large latent TGF-beta complexes (LL-TGF-beta)
      with subsequent deposition to the extracellular matrix (ECM). While a variety of
      mechanisms capable of activating latent TGF-beta in vitro have been described,
      the physiological conditions, which promote the activation of TGF-beta in vivo
      are poorly understood. Mink lung epithelial cells (Mv1Lu) are a widely used model
      for evaluation of the effects of exogenous TGF-beta both in transcriptional and
      growth inhibitor assays. We find here that apoptosis of Mv1Lu cells, induced
      either by staurosporine or serum deprivation, is accompanied by proteolytic
      processing of LL-TGF-beta and the activation of endogenous TGF-beta. Activation
      of TGF-beta preceded caspase-3 activation and was almost completely suppressed by
      the serine protease inhibitor, AEBSF. Both exogenous and endogenously activated
      TGF-betas were able to enhance the apoptotic response of Mv1Lu cells leading to
      potentiation of cell death. Potentiation of cell death by activated TGF-beta was
      associated with downregulation of Akt and p38 MAPK, which were both activated at
      the initial stages of Mv1Lu apoptosis and were suppressed by exogenous TGF-beta.
      Pharmacological interruption of either phosphoinositide-3-kinase (PI-3K)/Akt or
      p38 MAPK signaling by the specific inhibitors mimicked the effect of TGF-beta
      leading to potentiation of cell death. Current results suggest that proteolytic
      activation of endogenous TGF-beta is a component of the apoptotic response,
      capable of modulating the death of Mv1Lu cells by inhibition of both PI-3K/Akt
      and p38 MAPK-dependent survival pathways.

PMID- 16447254
TI  - Cerebrospinal fluid tau, A beta, and phosphorylated tau protein for the diagnosis
      of Alzheimer's disease.
AB  - The diagnosis of AD is still largely based on exclusion criteria of secondary
      causes and other forms of dementia with similar clinical pictures, than the
      diagnostic accuracy of AD is low. Improved methods of early diagnosis are needed,
      particularly because drugs treatment is more effective in the early stages of the
      disease. Recent research focused the attention to biochemical diagnostic markers
      (biomarkers) and according to the proposal of a consensus group on biomarkers,
      three candidate CSF markers reflecting the pathological AD processes, have
      recently been identified: total tau protein (t-tau), amyloid beta(1-42) protein
      (A beta42), and tau protein phosphorylated at AD-specific epitopes (p-tau).
      Several articles report reduced CSF levels of A beta42 and increased CSF levels
      of t-tau and p-tau in AD; the sensitivity and specificity of these data are able
      for discrimination of AD patients from controls. However, the specificity for
      other dementias is low. According to the literature analysis reported in the
      present review, we can conclude that the combination of the CSF markers and their
      ratios may significantly increase the specificity and the accuracy of AD
      diagnosis.

PMID- 16447255
TI  - Hydrogen bonding is the prime determinant of carboxyl pKa values at the N-termini
      of alpha-helices.
AB  - Experimentally determined mean pK(a) values of carboxyl residues located at the N
      termini of alpha-helices are lower than their overall mean values. Here, we
      perform three types of analyses to account for this phenomenon. We estimate the
      magnitude of the helix macrodipole to determine its potential role in lowering
      carboxyl pK(a) values at the N-termini. No correlation between the magnitude of
      the macrodipole and the pK(a) values is observed. Using the pK(a) program propKa
      we compare the molecular surroundings of 18 N-termini carboxyl residues versus
      233 protein carboxyl groups from a previously studied database. Although pK(a)
      lowering interactions at the N-termini are similar in nature to those encountered
      in other protein regions, pK(a) lowering backbone and side-chain hydrogen bonds
      appear in greater number at the N-termini. For both Asp and Glu, there are about
      0.5 more hydrogen bonds per residue at the N-termini than in other protein
      regions, which can be used to explain their lower than average pK(a) values.
      Using a QM-based pK(a) prediction model, we investigate the chemical environment
      of the two lowest Asp and the two lowest Glu pK(a) values at the N-termini so as
      to quantify the effect of various pK(a) determinants. We show that local
      interactions suffice to account for the acidity of carboxyl residues at the N
      termini. The effect of the helix dipole on carboxyl pK(a) values, if any, is
      marginal. Backbone amide hydrogen bonds constitute the single biggest contributor
      to the lowest carboxyl pK(a) values at the N-termini. Their estimated pK(a)
      lowering effects range from about 1.0 to 1.9 pK(a) units.

PMID- 16447256
TI  - Analysis of dystroglycan regulation and functions in mouse mammary epithelial
      cells and implications for mammary tumorigenesis.
AB  - Abnormalities in the interactions of cells with the extracellular matrix (ECM)
      play an important role in the development and progression of many types of cancer
      and are a hallmark of malignant transformation. The dystroglycan (DG) complex is
      a transmembrane glycoprotein that forms a continuous link from the ECM to the
      actin cytoskeleton, providing structural integrity and perhaps transducing
      signal, in a manner similar to integrins. Deregulated expression of DG has been
      reported in a variety of human malignancies and related to tumor differentiation
      and aggressiveness. In breast cancer, reduced DG expression has been associated
      with patient survival and with loss of differentiation of tumor cells. Limited
      data are available on DG physiology in epithelial cells. In this study, we used
      the HC11 spontaneously immortalized murine mammary epithelial cells to study DG
      function(s) and regulation in normal cells. We found that expression of DG
      protein and mRNA is cell-cycle and cell-density regulated in these cells.
      Moreover, expression of both DG subunits increased upon lactogenic
      differentiation of the HC11 cells. The turnover of cell-surface-expressed DG was
      evaluated in the same cells and half-life of DG subunits was evaluated to be
      about 12 h. DG-specific small inhibitory RNAs were used to analyze the effects of
      a reduced expression of DG in these cells. Cells in which DG expression was
      suppressed were growth inhibited, accumulated in the S-phase of the cell cycle,
      failed to undergo lactogenic differentiation, and displayed an increase in the
      percentage of apoptotic cells. Moreover, changes were observed in the expression
      and/or activity of several molecules involved in cell growth control. These
      results demonstrate that DG expression is tightly regulated in normal mammary
      epithelial cells and support the hypothesis that DG is involved in several
      functions other than structural integrity in these cells. This finding provides
      new insight into the roles played by DG in epithelial cell physiology and will
      contribute to our understanding of its involvement in the process of epithelial
      cell transformation.

PMID- 16447257
TI  - Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular
      endothelial cells.
AB  - Angiopoietin-2 (Ang2) is a Tie-2 ligand that destabilizes vascular structures,
      allowing for neovascularization or vessel regression depending on local vascular
      endothelial cell growth factor (VEGF) concentrations. Although various stimuli
      have been shown to affect Ang2 expression, information on the underlying
      mechanisms involved in Ang2 production in endothelial cells (EC) is just
      beginning to emerge. In the present study, we have used adenovirus-mediated gene
      transfer and pharmacological inhibitors to examine the role of the PTEN/PI3-K/Akt
      pathway on Ang2 release. Inhibition of PI3-kinase with wortmannin led to a
      stimulation of basal Ang2 release in EC, while overexpression of an active form
      of Akt reduced Ang2. In addition, adenovirus-mediated gene transfer of the
      phosphatase PTEN stimulated Ang2 release. Incubation of the cells with Ang1, an
      agent that activates the PI3-K/Akt pathway in EC, reduced Ang2 release. This
      effect of Ang1 could be prevented by wortmannin and LY-294002 pretreatment.
      Similarly, in VEGF-treated EC the increase in Ang2 production observed was
      greater in the presence of a PI3-K inhibitor. Our observations that PTEN acts as
      a positive modulator of Ang2 release, while activation of the PI3-K/Akt pathway
      downregulates Ang2, reveal an additional mechanism through which the PTEN/PI3
      K/Akt pathway could affect the angiogenic process.

PMID- 16447258
TI  - Human glioblastoma ADF cells express tyrosinase, L-tyrosine hydroxylase and
      melanosomes and are sensitive to L-tyrosine and phenylthiourea.
AB  - Melanocytes and neuroblasts share the property of transforming L-tyrosine through
      two distinct metabolic pathways leading to melanogenesis and catecholamine
      synthesis, respectively. While tyrosinase (TYR) activity has been shown to be
      expressed by neuroblastoma it remains to be established as to whether also
      glioblastomas cells are endowed with this property. We have addressed this issue
      using the human continuous glioblastoma cell line ADF. We demonstrated that these
      cells possess tyrosinase as well as L-tyrosine hydroxylase (TH) activity and
      synthesize melanosomes. Because the two pathways are potentially cyto-genotoxic
      due to production of quinones, semiquinones, and reactive oxygen species (ROS),
      we have also investigated the expression of the peroxisomal proliferators
      activated receptor alpha (PPARalpha) and nuclear factor-kB (NFkB) transcription
      factor as well the effect of L-tyrosine concentration on cell survival. We report
      that L-tyrosine down-regulates PPARalpha expression in ADF cells but not
      neuroblastoma and that this aminoacid and phenylthiourea (PTU) induces apoptosis
      in glioblastoma and neuroblastoma.

PMID- 16447259
TI  - Hepatitis A virus: from discovery to vaccines.
AB  - Hepatitis A virus (HAV), the causative agent of type A viral hepatitis, is an
      ancient human virus that was first identified almost 35 years ago. It has several
      characteristics that make it unique among the Picornaviridae, particularly in
      terms of its mechanisms of polyprotein processing and virion morphogenesis, and
      which likely contribute to its pathobiology. Although efficacious vaccines
      containing formalin-inactivated virus produced in cell culture have been licensed
      in multiple countries, their use has been limited by cost considerations. Changes
      in public health sanitation and generally increasing standards of living are
      leading to a decreasing incidence of acute hepatitis A worldwide, with the result
      that the prevalence of preexisting immunity among adults is declining in many
      regions. These changes in the epidemiology of HAV may paradoxically enhance the
      disease burden, as greater numbers of individuals become infected at older ages
      when disease is more likely to be clinically evident, thus providing greater
      incentives for vaccine utilization.

PMID- 16447260
TI  - Therapy of hepatitis B -- viral suppression or eradication?
AB  - The practicing clinician is currently faced with a number of treatment options
      for chronic hepatitis B. Beginning in 1998 with the licensing of lamivudine and
      subsequently adefovir, the treatment paradigm shifted from 4 to 6 months of
      conventional alfa interferon to a year of nucleoside analog therapy. However,
      prolonged treatment with nucleoside analogs is often needed to optimize
      virological response. Recently, a 48-week regimen of pegylated interferon for
      hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B has
      been shown to be effective, and long-term nucleoside analog therapy has been
      demonstrated to maintain viral suppression. These findings have added to the
      complexity of decision-making and have raised questions about whether a finite
      course of pegylated interferon or nucleoside analog therapy, with possible long
      term maintenance, is better as first-line therapy. Each of these fundamentally
      different approaches has advantages and limitations, and both have a place in the
      therapeutic armamentarium against chronic hepatitis B. Long-term therapy with
      nucleoside analogs, however, raises a number of practical concerns that have not
      been fully addressed as of yet. I will present evidence in support of the
      recommendation that antiviral therapy should ideally be directed toward achieving
      the highest rate of viral clearance with the shortest interval of treatment.

PMID- 16447261
TI  - Hepatitis C -- identifying patients with progressive liver injury.
AB  - Hepatitis C follows a variable course with some patients developing progressive
      liver fibrosis, cirrhosis and hepatocellular carcinoma, while others have minimal
      or no significant liver disease after decades of infection. Studies have
      identified both host and viral factors associated with disease progression. The
      importance of general factors such as age at infection, gender, immune status and
      alcohol consumption has long been recognized; however recently, polymorphisms in
      a wide array of genes have also been shown to be associated with progressive
      fibrosis. How specific viral proteins may contribute to disease progression has
      also been studied. This review highlights what is currently known about the
      factors associated with progressive liver injury in patients with hepatitis C. A
      greater understanding of the determinants of disease progression will hopefully
      lead to improved utilization of existing treatments and ultimately may aid in
      identification of new therapeutic targets.

PMID- 16447262
TI  - Therapy of hepatitis C: from empiricism to eradication.
AB  - The complications of chronic hepatitis C virus infection can be prevented by
      antiviral therapy. The initial choice of interferon alfa and, subsequently,
      ribavirin as potential treatments for chronic hepatitis C was empirical.
      Nevertheless, the combination of pegylated interferon alfa and ribavirin has
      become the standard treatment of chronic hepatitis C. Since the advent of
      interferon-based therapy, enormous progress has been made in understanding the
      mechanisms of treatment efficacy and failure, and in everyday patient management.
      The principal advances are: a better understanding of hepatitis C virus steady
      state kinetics and the antiviral mechanisms of interferon and ribavirin; easier
      treatment decisions thanks to novel assays to assess liver disease severity and
      the virological characteristics of infection; a better use of virological tests
      to tailor therapy; a better management of adverse effects; a better understanding
      of virological treatment failure; and a better management of "special"
      populations, including patients with decompensated cirrhosis and end-stage liver
      disease, liver transplant recipients, hemodialysis patients and renal transplant
      recipients, human immunodeficiency virus-coinfected patients, intravenous drug
      users and patients on opiate replacement therapy, or virological non responders
      to previous therapies. Steady-state HCV kinetics offers several potential targets
      for new drugs. These targets should ideally be hit simultaneously in order to
      achieve viral eradication within a reasonable time frame. Future drugs for HCV
      infection will belong to four main categories, including new interferons,
      alternatives to ribavirin, specific HCV inhibitors, and immune modulators. New
      treatments and vaccines might make it possible to eradicate HCV in the future.

PMID- 16447263
TI  - Growing importance of liver disease in HIV-infected persons.
AB  - Liver disease is a growing problem in HIV-infected persons. In those who are able
      to take antiretroviral therapy, the forms of liver disease have changed and their
      relative importance has increased. This review focuses on liver disease in HIV
      infected persons, caused by hepatitis C virus, hepatitis B virus, or treatment of
      HIV infection.

PMID- 16447264
TI  - Dynamic regulation and involvement of the heat shock transcriptional response in
      arsenic carcinogenesis.
AB  - The objective of this study is to better define induction of the heat shock
      response by arsenite, and to evaluation if induction of heat shock proteins
      (HSPs) contributes to the carcinogenic activity of arsenite. We show here that
      arsenite is a ubiquitous inducer of the heat shock response in mammalian cells:
      that it activated heat shock transcription factor 1 (HSF1) DNA-binding activity,
      enhanced hsp 70 promoter, and induced hsp70mRNA and synthesis of HSP chaperones.
      Using a high throughput hsp70 promoter-luciferase reporter assay, we observed a
      hormetic dose response where low concentrations of arsenite stimulated and high
      concentrations inhibited. Further, the response was time-dependent such that with
      longer times of incubation, the dose response shifted to the left. The effect of
      arsenite in inducing the hsp 70-luciferase reporter absolutely required a
      functional HSF1 as it was not observed in HSF1 minus cells but re-instated by
      expression of HSF1. Consistent with the suggestion that arsenic targets vicinal
      cysteine-SH, we showed that dithiothreitol blocked the effect of arsenite. Assays
      of cell viability and caspase showed that arsenite caused a dose-dependent
      increase in cell death by activation of caspase 3/7 and pre-induction of HSPs
      blunted these effects. Using anchorage independent cell growth as a late stage
      tumor promotion assay, we showed that low concentrations of arsenite had a growth
      promoting effect, which was enhanced by moderate heat shock. Our study provides
      evidence that induction of the heat shock response is a sensitive biomarker of
      arsenic exposure and that induction of HSPs likely contributes to the tumor
      promotion effect of arsenic.

PMID- 16447265
TI  - Bone morphogenetic protein 4 mediates bile duct ligation induced liver fibrosis
      through activation of Smad1 and ERK1/2 in rat hepatic stellate cells.
AB  - Bone morphogenetic proteins (BMPs) are the important cytokine involving in cell
      differentiation especially in bone morphogenesis. Hepatic stellate cells (HSCs)
      undergo a trans-differentiation during their activation after liver injury.
      Although it has been demonstrated that BMP2 and BMP4 significantly increased the
      abundance of smooth muscle alpha actin (alpha-SMA) in cultured HSCs, the
      expression of BMPs has not been examined during the activation of HSCs. In
      current study, we documented the expression of BMP4 in bile duct ligation (BDL)
      rats and HSCs in culture. We have found that the expression of BMP4 was
      significantly elevated in the liver of BDL rats. The increase in BMP4 protein
      showed two peaks during 6 weeks after BDL. The expression and phosphorylation of
      Smad1, ERK1/2 and p38 were also elevated after BDL. Moreover, there was a gradual
      elevation of BMP4 mRNA abundance during 24 days' in vitro culture of HSCs.
      Furthermore, BMP4 stimulated phosphorylation of Smad1 and ERK1/2 in HSCs. In
      conclusion, BMP4 expression was significantly increased in the liver of BDL rats
      and HSCs in culture. These findings indicate that BMP4 may mediate HSC activation
      through activation of Smad1 and ERK1/2.

PMID- 16447266
TI  - Assembly of nuclear matrix-bound protein complexes involved in non-homologous end
      joining is induced by inhibition of DNA topoisomerase II.
AB  - Topoisomerases maintain the DNA structure by relieving the torsional stress and
      alleviating other topological problems occurring in DNA during transcription and
      replication. Topoisomerase II appears to have a close association with the family
      of proteins involved in the organization of chromatin in a series of loops on the
      proteinaceous chromosomal matrix. Beyond its physiological functions,
      topoisomerase II is the target for some of the most active anticancer drugs.
      Inhibition of the topoisomerase II function can result in DNA double-strand
      breaks (DSBs) and, thus, lead to chromosomal translocations. The earliest event
      during DSB repair is phosphorylation of histone H2AX at S139 (so-called
      gammaH2AX) which is believed to serve as a focal point for the assembly of repair
      proteins at the DSB. In this work, we have demonstrated the formation of
      gammaH2AX foci in two human cell lines--K562 and HeLa--after suppression of
      topoisomerase II activity with etoposide. Furthermore, these foci remained
      visible at nuclear matrices and colocalized with the major components of non
      homologous end joining (NHEJ) system of DSBs repair. Thus, inhibition of
      topoisomerase II activity triggers assembly of NHEJ complexes at the nuclear
      matrix.

PMID- 16447267
TI  - Immunohistochemical evaluation of pRb2/p130, VEGF, EZH2, p53, p16, p21waf-1, p27,
      and PCNA in Barrett's esophagus.
AB  - Control of the G1/S-phase transition as well as angiogenic switch are two of the
      most studied mechanisms in cancer. The current study examined the correlation
      between the immunohistochemical expression of pRb2/p130, VEGF, EZH2, p53, p16,
      p21waf-1, p27, and PCNA in Barrett's esophagus (BE). Overall, p53 showed a much
      higher expression in BE patients (up to 50%) than in controls (1-10%) (P <
      0.005). Also p21 showed a downregulation in BE when compared to normal esophagus
      (70% of cells vs. 65%), but the difference did not show any statistical
      significance (P = 0.45). pRb2/p130 was detected in 80% of cells in normal
      controls, but showed positive in only 20% of cells in BE biopsies. Additionally,
      Rb2/p130 expression was inversely correlated to that of VEGF, EZH2, and PCNA (P <
      0.0001, P = 0.0032, P < 0.001, respectively). p27 stained more intensely and in a
      widespread manner (70%) cells in normal esophageal tissues but about only 30% in
      BE samples (P < 0.001). Lastly, in accordance with other reports, we also found
      p16 expressed by immunohistochemistry at high levels in normal controls and at
      low levels in BE (P < 0.001). In conclusion, p16, p21, p27, and p53 staining
      confirmed previously published data. Interestingly, pRb2/p130 expression was
      found significantly decreased in metaplastic epithelium compared to normal
      controls and showed significant inverse correlation with the expression of other
      markers, such as VEGF, EZH2, and PCNA. These data, taken together, indicate that
      these molecular events occurring in Barrett's metaplasia (BM) may represent one
      of the many steps taking place during esophageal malignant progression such as
      impairment of cell-cycle control, altered differentiation, and unbalanced
      angiogenesis.

PMID- 16447268
TI  - Age-related alterations in hippocampal spines and deficiencies in spatial memory
      in mice.
AB  - Alterations in neuronal morphology occur in the brain during normal aging, but
      vary depending on neuronal cell types and brain regions. Such alterations have
      been related to memory and cognitive impairment. Changes in hippocampal spine
      densities are thought to represent a morphological correlate of altered brain
      functions associated with hippocampal-dependent learning and memory. We therefore
      have analyzed the impact of aging on different hippocampal-dependent learning
      tasks and on changes in dendritic spines of CA1 hippocampal and dentate gyrus
      neurons by analyzing adult (6-7 months) and aged (21-22 months) C57/Bl6 mice. We
      found a significant decrease in spine numbers of basal CA1 dendrites and
      decreases in spine length of apical dendrites of CA1 and dentate gyrus neurons.
      Furthermore, aged mice exhibited significant deficits in hippocampus-dependent
      learning tasks, such as the probe trial of the Morris water maze and T maze
      learning. Given the fact that there is no neuronal loss in the hippocampus in
      aged mice (von Bohlen und Halbach and Unsicker [2002] Eur. J. Neurosci. 16:2434
      2440), we suggest that the memory and cognitive decline in the context of aging
      may be accompanied by rather subtle anatomical changes, such as numbers and
      morphology of dendritic spines.

PMID- 16447269
TI  - Role of extracellular-regulated kinase and c-Jun NH2-terminal kinase in 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine-induced neurofilament phosphorylation.
AB  - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes
      selective degeneration of dopaminergic neurons in which the c-Jun NH2-terminal
      kinase (JNK) signalling cascade has been implicated. We have employed a
      differentiated mouse neuroblastoma N2a cell model to investigate the involvement
      of JNK and extracellular-regulated kinase (ERK) in MPTP-mediated toxicity and
      their role in neurofilament heavy chain (NF-H) phosphorylation. Acute treatment
      with a cytotoxic MPTP concentration (5 mM) caused rapid and sustained JNK
      phosphorylation and ERK dephosphorylation, accompanied by cell death. In
      contrast, subcytotoxic concentrations of 10 microM MPTP resulted in lower,
      transient JNK activation in the presence of sustained ERK activity. This resulted
      in an aberrant increase in a phosphorylation-dependent NF-H epitope, perikaryal
      accumulation of NF-H, and loss of axon-like processes, prior to cell death.
      Inhibition of MEK kinase, using PD98059, showed that MEK 1/2 or the downstream
      kinase, ERK, is required for N2a cell differentiation, NF-H phosphorylation and
      survival. Indeed, MPTP-induced cell death was exacerbated by the presence of
      PD98059. However, in the presence of MPTP, reducing JNK activity by using an
      upstream specific mixed-lineage kinase inhibitor (CEP-11004) significantly
      attenuated aberrant NF-H phosphorylation and perikaryal NF-H accumulation and
      maintained axon-like processes, in addition to attenuating cell death. This study
      reports a switch in the predominant kinase involved in NF phosphorylation in a
      neuronal cell model and may have implications for the formation of inclusions.
      Our studies provide further evidence that modulation of the JNK pathway could
      have a role in alleviating neuronal cell death.

PMID- 16447270
TI  - 25 years of Hepatology.

PMID- 16447271
TI  - The liver as an immunological organ.
AB  - The liver is a unique anatomical and immunological site in which antigen-rich
      blood from the gastrointestinal tract is pressed through a network of sinusoids
      and scanned by antigen-presenting cells and lymphocytes. The liver's lymphocyte
      population is selectively enriched in natural killer and natural killer T cells
      which play critical roles in first line immune defense against invading
      pathogens, modulation of liver injury and recruitment of circulating lymphocytes.
      Circulating lymphocytes come in close contact to antigens displayed by
      endothelial cells, Kupffer cells and liver resident dendritic cells in the
      sinusoids. Circulating lymphocytes can also contact hepatocytes directly, because
      the sinusoidal endothelium is fenestrated and lacks a basement membrane. This
      unique anatomy of the liver may facilitate direct or indirect priming of
      lymphocytes, modulate the immune response to hepatotrophic pathogens and
      contribute to some of the unique immunological properties of this organ,
      particularly its capacity to induce antigen-specific tolerance.

PMID- 16447272
TI  - Apoptosis and necrosis in the liver: a tale of two deaths?
AB  - Death of hepatocytes and other hepatic cell types is a characteristic feature of
      liver diseases as diverse as cholestasis, viral hepatitis, ischemia/reperfusion,
      liver preservation for transplantation and drug/toxicant-induced injury. Cell
      death typically follows one of two patterns: oncotic necrosis and apoptosis.
      Necrosis is typically the consequence of acute metabolic perturbation with ATP
      depletion as occurs in ischemia/reperfusion and acute drug-induced
      hepatotoxicity. Apoptosis, in contrast, represents the execution of an ATP
      dependent death program often initiated by death ligand/death receptor
      interactions, such as Fas ligand with Fas, which leads to a caspase activation
      cascade. A common event leading to both apoptosis and necrosis is mitochondrial
      permeabilization and dysfunction, although the mechanistic basis of mitochondrial
      injury may vary in different settings. Prevention of these modes of cell death is
      an important target of therapy, but controversies still exist regarding which
      mode of cell death predominates in various forms of liver disease and injury.
      Resolution of these controversies may come with the recognition that apoptosis
      and necrosis frequently represent alternate outcomes of the same cellular
      pathways to cell death, especially for cell death mediated by mitochondrial
      permeabilization. An understanding of processes leading to liver cell death will
      be important for development of effective interventions to prevent hepatocellular
      death leading to liver failure and to promote cancer and stellate cell death in
      malignancy and fibrotic disease.

PMID- 16447273
TI  - Alcohol and oxidative liver injury.
AB  - Acute and chronic ethanol treatment has been shown to increase the production of
      reactive oxygen species, lower cellular antioxidant levels, and enhance oxidative
      stress in many tissues, especially the liver. Ethanol-induced oxidative stress
      plays a major role in the mechanisms by which ethanol produces liver injury. Many
      pathways play a key role in how ethanol induces oxidative stress. This review
      summarizes some of the leading pathways and discusses the evidence for their
      contribution to alcohol-induced liver injury. Many of the seminal reports in this
      topic have been published in Hepatology , and it is fitting to review this
      research area for the 25th Anniversary Issue of the Journal.

PMID- 16447274
TI  - Liver regeneration.
AB  - During liver regeneration after partial hepatectomy, normally quiescent
      hepatocytes undergo one or two rounds of replication to restore the liver mass by
      a process of compensatory hyperplasia. A large number of genes are involved in
      liver regeneration, but the essential circuitry required for the process may be
      categorized into three networks: cytokine, growth factor and metabolic. There is
      much redundancy within each network, and intricate interactions exist between
      them. Thus, loss of function from a single gene rarely leads to complete blockage
      of liver regeneration. The innate immune system plays an important role in the
      initiation of liver regeneration after partial hepatectomy, and new cytokines and
      receptors that participate in initiation mechanisms have been identified.
      Hepatocytes primed by these agents readily respond to growth factors and enter
      the cell cycle. Presumably, the increased metabolic demands placed on hepatocytes
      of the regenerating liver are linked to the machinery needed for hepatocyte
      replication, and may function as a sensor that calibrates the regenerative
      response according to body demands. In contrast to the regenerative process after
      partial hepatectomy, which is driven by the replication of existing hepatocytes,
      liver repopulation after acute liver failure depends on the differentiation of
      progenitor cells. Such cells are also present in chronic liver diseases, but
      their contribution to the production of hepatocytes in those conditions is
      unknown. Most of the new knowledge about the molecular and cellular mechanisms of
      liver regeneration is both conceptually important and directly relevant to
      clinical problems.

PMID- 16447275
TI  - Reversal of hepatic fibrosis -- fact or fantasy?
AB  - The prospect of reversing hepatic fibrosis has generated great interest now that
      basic science advances are being translated into promising new antifibrotic
      therapies. It is appropriate to recognize both the historical advances that
      created the framework for these successes, and the important role that Hepatology
      has played in disseminating them. A sense of urgency underlies this effort as the
      epidemics of HCV and NASH are becoming associated with advancing fibrosis. To
      maintain progress and minimize confusion among investigators and clinicians it is
      essential to standardize terms referring to fibrosis 'reversal' and 'regression.'
      There must also be rapid optimization of non-invasive markers of fibrosis to
      relieve this current bottleneck to conducting clinical trials. Progress in
      identifying genetic determinants of fibrosis could further refine patient
      selection for clinical trials and shorten their duration, as well as unearthing
      new directions of scientific inquiry. Realistic expectations for successful anti
      fibrotic therapies reflect solid evidence of fibrosis regression in patients
      treated effectively for viral liver disease, as well as growing clarity in the
      understanding mechanisms of extracellular matrix production and degradation. The
      paradigms of stellate cell activation and apoptosis remain valuable frameworks
      for understanding pathways of hepatic fibrogenesis and fibrosis regression,
      respectively. Continued progress is essential in order to identify the
      determinants and dynamics of fibrosis reversibility, to discover additional
      targets for anti-fibrotic therapy, and to develop customized multi-drug regimens.
      These advances are sure to be captured in the next 25 years by Hepatology , and
      to profoundly impact the prognosis of patients with chronic liver disease.

PMID- 16447276
TI  - Aquaporins in the hepatobiliary system.
AB  - The review focuses on the potential physiological and pathophysiological roles of
      aquaporins (AQPs), a family of water channel proteins, in the hepatobiliary
      system. Among 13 aquaporins (AQP0-AQP12) cloned in mammals, seven AQPs have been
      identified in the liver and biliary tree. Accumulating evidence suggests that
      AQPs are likely involved in canalicular and ductal bile secretion,
      gluconeogenesis and microbial infection and may have other novel roles that
      affect liver function.

PMID- 16447277
TI  - First do no harm. 2005.

PMID- 16447278
TI  - Reflections on the first five years of Hepatology , 1981-1986.

PMID- 16447279
TI  - An editor's look-back.

PMID- 16447280
TI  - Hepatology over the years.

PMID- 16447281
TI  - An enhanced elastic network model to represent the motions of domain-swapped
      proteins.
AB  - Domain swapping is a process where two (or more) protein molecules form a dimer
      (or higher oligomer) by exchanging an identical domain. In this article, based on
      the observation that domains are rigid and hinge loops are highly flexible, we
      propose a new Elastic Network Model, domain-ENM, for domain-swapped proteins. In
      this model, the rigidity of domains is taken into account by using a larger
      spring constant for intradomain contacts. The large-scale transition of domain
      swapping is then novelly decomposed into the relative motion between the rigid
      domains (only 6 degrees of freedom) plus the internal fluctuations of each
      domain. Consequently, this approach has the potential to produce much more
      meaningful transition pathways than other simulation approaches that try to find
      pathways in a search space of large numbers of dimensions. In this article, we
      also propose a new way to define the overlap measure. Past approaches used an
      inappropriate comparison of the large-scale conformation displacement against the
      computed infinitesimal motions of modes. Here, we propose an infinitesimal
      version of the large-scale conformation change and then compare it with the modes
      of motions. As a result, we obtain much better overlap values. Using this new
      overlap definition, we are also able for the first time to give a clear,
      intuitive explanation why "open" forms tend to produce better overlap values than
      "closed" forms with traditional ENMs. Finally, as an application, we present a
      simple approach to show how domain-ENM can be used to generated transition
      pathways for domain-swapped proteins.

PMID- 16447282
TI  - Survey of inward ionic currents acquired by the cochleovestibular ganglion of the
      early-aged embryonic chick.
AB  - The acquisition of ion channels is critical to the formation of neuronal pathways
      in the peripheral and central nervous systems. This study describes the different
      types of inward currents (Ii) recorded from the soma of isolated
      cochleovestibular ganglion (CVG) cells of the embryonic chicken, Gallus gallus.
      Cells were isolated for whole-cell tight-seal recording from embryonic day (ED)
      3, an age when the CVG is a cell cluster, to ED 9, an age when the cochlear and
      vestibular ganglia (CG, VG) are distinct structures. Results show Na+ and Ca2+
      currents (INa and ICa) are acquired by ED 3, although INa dominates with greater
      density levels that peak by ED 6-7 in VG neurons. In the CG, INa acquisition is
      slower, reaching peak values by ED 8-9. Isolation of ICa, using Ba2+ as the
      charge carrier, showed both transient (IBaT)- and sustained (IBaL)-type currents
      on ED 3. Unlike INa, IBa density varied with age and ganglion. Total IBa
      increased steadily, showing a decline only in CG cells on ED 8-9 as a result of a
      decrease in IBaT. IBaL density increased over time, reaching a maximum on ED 6-7
      in VG cells, followed by a decline on ED 8-9. In comparison, IBaL in CG neurons,
      did not increase significantly beyond mean values measured on ED 5. The early
      onset of these currents and the variations in Ca2+ channel expression between the
      ganglia suggests that intracellular signals relevant to phenotypic
      differentiation begin within these early time frames.

PMID- 16447283
TI  - Acute depletion of reduced glutathione causes extensive carbonylation of rat
      brain proteins.
AB  - This study was aimed at establishing whether oxidative stress induced by acute
      depletion of brain glutathione (GSH) is sufficient to generate protein carbonyls
      (PCOs). To this end, rat brain slices were incubated separately with the GSH
      depletors 1,3-bis[2-chloroethyl]-1-nitrosourea (BCNU) and diethyl maleate (DEM),
      and protein carbonylation was assessed on Western blots after derivatization with
      dinitrophenyl hydrazine. Incubation with 1 mM BCNU or 10 mM DEM for 2 hr
      decreased GSH levels by > 70%. Under these conditions the carbonylation of
      several proteins (40-120 kDa) increased by 2-3 fold. Isolation of carbonylated
      proteins showed that augmented PCOs represents a rise in the amount of oxidized
      protein. The iron chelator deferoxamine, the superoxide scavenger rutin and the
      H2O2 quencher dimethylthiourea all prevented DEM-induced protein carbonylation
      and lipid peroxidation (TBARS), indicating that the underlying mechanism involves
      the iron-catalyzed generation of hydroxyl radicals from H(2)O(2) (Fenton
      reaction). Inhibition of catalase activity with sodium azide and aminotriazole,
      and glutathione peroxidase activity with mercaptosuccinic acid did not increase
      PCOs or TBARS, suggesting that increased production of reactive oxygen species
      (ROS) rather than compromised cellular antioxidant defenses is the cause for the
      accumulation of H2O2 after GSH depletion. PCO formation was not affected by the
      xanthine oxidase inhibitor oxypurinol but it was reduced by SKF-525A and carbonyl
      cyanide 3-chlorophenylhydrazone, indicating that the microsomal monooxygenase
      system and the mitochondrial electron transport system are the major sources of
      ROS. Consistent with these findings, subcellular fractionation studies showed
      that mitochondria and synaptosomes are the major PCO-containing organelles. These
      results were also supported by the anatomic distribution of PCOs in brain. Our
      observations may be important in the context of multiple sclerosis where
      decreased GSH, mitochondrial dysfunction, excessive production of ROS, and
      increased protein carbonylation have all been reported.

PMID- 16447284
TI  - Temporal pattern of C1q deposition after transient focal cerebral ischemia.
AB  - Recent studies have focused on elucidating the contribution of individual
      complement proteins to post-ischemic cellular injury. As the timing of complement
      activation and deposition after cerebral ischemia is not well understood, our
      study investigates the temporal pattern of C1q accumulation after experimental
      murine stroke. Brains were harvested from mice subjected to transient focal
      cerebral ischemia at 3, 6, 12, and 24 hr post reperfusion. Western blotting and
      light microscopy were employed to determine the temporal course of C1q protein
      accumulation and correlate this sequence with infarct evolution observed with TTC
      staining. Confocal microscopy was utilized to further characterize the cellular
      localization and characteristics of C1q deposition. Western Blot analysis showed
      that C1q protein begins to accumulate in the ischemic hemisphere between 3 and 6
      hr post-ischemia. Light microscopy confirmed these findings, showing concurrent
      C1q protein staining of neurons. Confocal microscopy demonstrated co-localization
      of C1q protein with neuronal cell bodies as well as necrotic cellular debris.
      These experiments demonstrate the accumulation of C1q protein on neurons during
      the period of greatest infarct evolution. This data provides information
      regarding the optimal time window during which a potentially neuroprotective anti
      C1q strategy is most likely to achieve therapeutic success.

PMID- 16447285
TI  - Natural history of chronic hepatitis B virus infection: what we knew in 1981 and
      what we know in 2005.
AB  - Remarkable progress has been made in our understanding of the natural history of
      chronic hepatitis B virus (HBV) infection in the past 25 years. Availability of
      sensitive HBV DNA assays and application of sophisticated immunological
      techniques led to the recognition that HBV replication persists throughout the
      course of chronic HBV infection, and host immune response plays a pivotal role in
      HBV-related liver disease. Knowledge of the HBV genome organization and
      replication cycle led to the unraveling of HBV genotypes and molecular variants,
      which contribute to the heterogeneity in outcome of chronic HBV infection. The
      natural course of chronic HBV infection is now perceived as consisting of 4
      phases: immune tolerance, immune clearance [hepatitis B e antigen (HBeAg)
      positive chronic hepatitis], inactive carrier state, and reactivation (HBeAg
      negative chronic hepatitis B). Understanding the dynamic nature of chronic HBV
      infection is crucial in the management of HBV carriers and underscores the need
      for long-term monitoring. Accumulating evidence indicates that antiviral therapy
      can prevent progression of HBV-related liver disease, particularly among patients
      with sustained response. Newer antiviral therapies with improved efficacy and
      decreased risk of resistance may lead to a complete revision of the chapter on
      the natural history of chronic HBV infection on the occasion of the golden
      jubilee of Hepatology.

PMID- 16447286
TI  - Viral hepatitis.

PMID- 16447287
TI  - Nonalcoholic fatty liver disease: from steatosis to cirrhosis.
AB  - Nonalcoholic steatohepatitis (NASH), the lynchpin between steatosis and cirrhosis
      in the spectrum of nonalcoholic fatty liver disorders (NAFLD), was barely
      recognized in 1981. NAFLD is now present in 17% to 33% of Americans, has a
      worldwide distribution, and parallels the frequency of central adiposity,
      obesity, insulin resistance, metabolic syndrome and type 2 diabetes. NASH could
      be present in one third of NAFLD cases. Age, activity of steatohepatitis, and
      established fibrosis predispose to cirrhosis, which has a 7- to 10-year liver
      related mortality of 12% to 25%. Many cases of cryptogenic cirrhosis are likely
      endstage NASH. While endstage NAFLD currently accounts for 4% to 10% of liver
      transplants, this may soon rise. Pathogenic concepts for NAFLD/NASH must account
      for the strong links with overnutrition and underactivity, insulin resistance,
      and genetic factors. Lipotoxicity, oxidative stress, cytokines, and other
      proinflammatory mediators may each play a role in transition of steatosis to
      NASH. The present "gold standard" management of NASH is modest weight reduction,
      particularly correction of central obesity achieved by combining dietary measures
      with increased physical activity. Whether achieved by "lifestyle adjustment" or
      anti-obesity surgery, this improves insulin resistance and reverses steatosis,
      hepatocellular injury, inflammation, and fibrosis. The same potential for
      "unwinding" fibrotic NASH is indicated by studies of the peroxisome proliferation
      activator receptor (PPAR)-gamma agonist "glitazones," but these agents may
      improve liver disease at the expense of worsening obesity. Future challenges are
      to approach NAFLD as a preventive public health initiative and to motivate
      affected persons to adopt a healthier lifestyle.

PMID- 16447288
TI  - Noninvasive measures of liver fibrosis.
AB  - As novel therapies for liver fibrosis evolve, non-invasive measurement of liver
      fibrosis will be required to help manage patients with chronic liver disease.
      Although liver biopsy is the current and time-honored gold standard for
      measurement of liver fibrosis, it is poorly suited to frequent monitoring because
      of its expense and morbidity, and its accuracy suffers from sampling variation.
      At the current writing, serum markers and imaging methods are available and
      increasingly in use as alternatives to biopsy. However, many questions remain
      about their indications, accuracy, and cost-effectiveness, and more investigation
      is required before they are put into widespread use. The development of safe,
      inexpensive, and reliable noninvasive fibrosis measurement tools remains a
      research priority in clinical hepatology.

PMID- 16447289
TI  - The hyperdynamic circulation of chronic liver diseases: from the patient to the
      molecule.
AB  - The hyperdynamic circulatory syndrome observed in chronic liver diseases is a
      great example of research that originated from clinical observations and
      progressed in the last 50 years from the patient to the experimental laboratory.
      Our knowledge has evolved from the patient to the molecule, using experimental
      models that serve as a source for understanding the complex pathophysiological
      mechanisms that govern this complex syndrome. We now know that progressive
      vasodilatation is central to the detrimental effects observed in multiple organs.
      Although nitric oxide has been shown to be the primary vasodilator molecule in
      these effects, other molecules also participate in the complex mechanisms of
      vasodilatation. This review summarizes three major areas: first, clinical
      observation in patients; second, experimental models used to study the
      hyperdynamic circulatory syndrome; and third, the vasodilator molecules that play
      roles in vascular abnormalities observed in portal hypertension.

PMID- 16447291
TI  - Functional genomics of hepatocellular carcinoma.
AB  - The majority of DNA-microarray based gene expression profiling studies on human
      hepatocellular carcinoma (HCC) has focused on identifying genes associated with
      clinicopathological features of HCC patients. Although notable success has been
      achieved, this approach still faces significant challenges due to the
      heterogeneous nature of HCC (and other cancers) as well as the many confounding
      factors embedded in gene expression profile data. However, these limitations are
      being overcome by improved bioinformatics and sophisticated analyses. Also,
      application of cross comparison of multiple gene expression data sets from human
      tumors and animal models are facilitating the identification of critical
      regulatory modules in the expression profiles. The success of this new
      experimental approach, comparative functional genomics, suggests that integration
      of independent data sets will enhance our ability to identify key regulatory
      elements in tumor development. Furthermore, integrating gene expression profiles
      with data from DNA sequence information in promoters, array-based CGH, and
      expression of non-coding genes (i.e., microRNAs) will further increase the
      reliability and significance of the biological and clinical inferences drawn from
      the data. The pace of current progress in the cancer profiling field, combined
      with the advances in high-throughput technologies in genomics and proteomics, as
      well as in bioinformatics, promises to yield unprecedented biological insights
      from the integrative (or systems) analysis of the combined cancer genomics
      database. The predicted beneficial impact of this "new integrative biology" on
      diagnosis, treatment and prevention of liver cancer and indeed cancer in general
      is enormous.

PMID- 16447290
TI  - Autoimmune hepatitis, from mechanisms to therapy.
AB  - In 1950, Waldenstrom was the first to describe a chronic form of hepatitis in
      young women. Subsequently, the disease was found to be associated with other
      autoimmune syndromes and was later termed "lupoid hepatitis" because of the
      presence of antinuclear antibodies. In 1965, it became designated by Mackay et
      al. as "autoimmune hepatitis" at an international meeting, at which the general
      concept of autoimmunity was endorsed by the scientific community. In the early
      1960s and 1970s, the value of immunosuppressive therapy with glucocorticoids
      and/or azathioprine was well documented in several studies. The original
      association of autoimmune hepatitis (AIH) and HLA alleles, which has remarkably
      stood the test of time, was published in 1972. In the 1970s and 1980s, several
      autoantibodies were identified in patients with autoimmune hepatitis directed
      against proteins of the endoplasmatic reticulum expressed in liver and kidney and
      against soluble liver antigens. Subsequently, the molecular targets of these
      antibodies were identified and more precisely characterized. In the last two
      decades many additional pieces of the AIH puzzle have been collected leading to
      the identification of additional antibodies and genes associated with AIH and to
      the emergence of new therapeutic agents. Meanwhile, the immunoserological and
      genetic heterogeneity of AIH is well established and it has become obvious that
      clinical manifestations, disease behavior, and treatment outcome may vary by
      racial groups, geographical regions and genetic predisposition. Currently, the
      International Autoimmune hepatitis group is endorsing multi-center collaborative
      studies to more precisely define the features at disease presentation and to
      define prognostic indices and appropriate treatment algorithms. Given the
      importance of serological testing, the IAHG is also working on guidelines and
      procedures for more reliable and standardized testing of autoantibodies.

PMID- 16447293
TI  - Liver biology and pathobiology.

PMID- 16447292
TI  - Liver stem cells and prospects for liver reconstitution by transplanted cells.
AB  - Although it was proposed almost 60 years ago that the adult mammalian liver
      contains hepatic stem cells, this issue remains controversial. Part of the
      problem is that no specific marker gene unique to the adult hepatic stem cell has
      yet been identified, and regeneration of the liver after acute injury is achieved
      through proliferation of adult hepatocytes and does not require activation or
      proliferation of stem cells. Also, there are differences in the expected
      properties of stem versus progenitor cells, and we attempt to use specific
      criteria to distinguish between these cell types. We review the evidence for each
      of these cell types in the adult versus embryonic/fetal liver, where tissue
      specific stem cells are known to exist and to be involved in organ development.
      This review is limited to studies directed toward identification of hepatic
      epithelial stem cells and does not address the controversial issue of whether
      stem cells derived from the bone marrow have hepatocytic potential, a topic that
      has been covered extensively in other recent reviews.

PMID- 16447294
TI  - Liver failure and liver disease.

PMID- 16447296
TI  - Self-assembled bidentate ligands for Ru-catalyzed anti-Markovnikov hydration of
      terminal alkynes.

PMID- 16447297
TI  - Heterocyclic carbenes.

PMID- 16447298
TI  - Personalized immunotherapy for the treatment of non-Hodgkin's lymphoma: a
      promising approach.
AB  - The efficacy of immunotherapeutic strategies for the treatment of lymphoid
      malignancies has been demonstrated in recent years. In patients with B-cell
      lymphomas, particularly indolent lymphoma, the use of passive immunotherapy, such
      as the anti-CD20 monoclonal antibody rituximab, has made an impressive impact on
      patient outcome. Personalized immunotherapy, a method that triggers the immune
      system to mount a response against tumor cells, has shown promising results in
      early clinical trials in hematologic malignancies. This therapeutic modality
      appears safe, with the most common adverse events being transient, local
      reactions at the site of injection. Furthermore, personalized immunotherapy has
      the potential to generate immunologic memory, which could provide prolonged
      remission. Currently, 3 large phase III studies are evaluating the efficacy and
      safety of personalized immunotherapy in patients with follicular lymphoma. It is
      hoped that the results of these studies will lead to the incorporation of this
      promising approach into the standard treatment of patients with lymphoma.

PMID- 16447299
TI  - Hepatitis C: who should be treated?

PMID- 16447295
TI  - The unfinished legacy of liver transplantation: emphasis on immunology.
AB  - Liver transplantation radically changed the philosophy of hepatology practice,
      enriched multiple areas of basic science, and had pervasive ripple effects in
      law, public policy, ethics, and theology. Why organ engraftment was feasible
      remained enigmatic, however, until the discovery in 1992 of donor leukocyte
      microchimerism in long-surviving liver, and other kinds of organ recipients.
      Following this discovery, the leukocyte chimerism-associated mechanisms were
      elucidated that directly linked organ and bone marrow transplantation and
      eventually clarified the relationship of transplantation immunology to the
      immunology of infections, neoplasms, and autoimmune disorders. We describe here
      how the initially controversial paradigm shift mandated revisions of cherished
      dogmas. With the fresh insight, the reasons for numerous inexplicable phenomena
      of transplantation either became obvious or have become susceptible to
      discriminate experimental testing. The therapeutic implications of the "new
      immunology" in hepatology and in other medical disciplines, have only begun to be
      explored. Apart from immunology, physiologic investigations of liver
      transplantation have resulted in the discovery of growth factors (beginning with
      insulin) that are involved in the regulation of liver size, ultrastructure,
      function, and the capacity for regeneration. Such studies have partially
      explained functional and hormonal relationships of different abdominal organs,
      and ultimately they led to the cure or palliation by liver transplantation of
      more than 2 dozen hepatic-based inborn errors of metabolism. Liver
      transplantation should not be viewed as a purely technologic achievement, but
      rather as a searchlight whose beams have penetrated the murky mist of the past,
      and continue to potentially illuminate the future.

PMID- 16447300
TI  - Methods in pharmacoepidemiology: time-varying drug effects revisited.

PMID- 16447303
TI  - Structurally diagnostic ion/molecule reactions: class and functional-group
      identification by mass spectrometry.
AB  - This article discusses the application of gas-phase ion/molecule reactions for
      fine structural elucidation in mass spectrometry. This approach is illustrated
      via a representative collection of class- and functional group-selective
      reactions, a few of historical relevance as well as by more recent and
      instructive examples, and their applications. The focus is on reactions performed
      under well-controlled conditions of sequential mass spectrometry, discussing key
      mechanistic details and potential applications. Recent and innovative strategies
      that allow these reactions to be performed under ambient conditions, making this
      fast, selective and sensitive approach for structural investigation much more
      generally applicable, are also discussed.

PMID- 16447304
TI  - Sensitivity analysis and external adjustment for unmeasured confounders in
      epidemiologic database studies of therapeutics.
AB  - BACKGROUND: Large health care utilization databases are frequently used to
      analyze unintended effects of prescription drugs and biologics. Confounders that
      require detailed information on clinical parameters, lifestyle, or over-the
      counter medications are often not measured in such datasets, causing residual
      confounding bias. OBJECTIVE: This paper provides a systematic approach to
      sensitivity analyses to investigate the impact of residual confounding in
      pharmacoepidemiologic studies that use health care utilization databases.
      METHODS: Four basic approaches to sensitivity analysis were identified: (1)
      sensitivity analyses based on an array of informed assumptions; (2) analyses to
      identify the strength of residual confounding that would be necessary to explain
      an observed drug-outcome association; (3) external adjustment of a drug-outcome
      association given additional information on single binary confounders from survey
      data using algebraic solutions; (4) external adjustment considering the joint
      distribution of multiple confounders of any distribution from external sources of
      information using propensity score calibration. CONCLUSION: Sensitivity analyses
      and external adjustments can improve our understanding of the effects of drugs
      and biologics in epidemiologic database studies. With the availability of easy-to
      apply techniques, sensitivity analyses should be used more frequently,
      substituting qualitative discussions of residual confounding.

PMID- 16447305
TI  - Prolonged effect of endorphin treatment during pregnancy in the rat on the
      histamine content of immune cells of F1 and F2 offspring generations.
AB  - Female rats were treated with beta-endorphin on the 19th day of pregnancy and the
      histamine content of immune cells (blood lymphocytes; peritoneal lymphocytes,
      monocyte-macrophage-granulocyte group, mast cells; thymic lymphocytes) of the 7
      week-old progenies (F1 generation) was studied using a flow-cytometric
      immunocytochemical technique. In an other group, female F1 progenies of endorphin
      treated mothers were mated with control males and the F2 generation was monitored
      for histamine content similar to the F1. In the F1 generation each cell type,
      except peritoneal and blood lymphocytes, contained significantly more histamine
      than the control cells. In the F2 generation only mast cells contained
      significantly more histamine relative to the appropriate control. This means that
      the effect of endorphin (hormonal) imprinting is transmitted transgenerationally,
      but with decreasing intensity however. Mast cells retained the effect of
      imprinting for longer than the other cells. The results are compared with the
      levels of serotonin in similarly treated animals, studied in earlier experiments.
      As the endorphin level can be elevated during pregnancy (by pain, traumatization,
      or other stress conditions) this can the set biogenic amine content of adult
      immune cells.

PMID- 16447306
TI  - Active for Life After Cancer: a randomized trial examining a lifestyle physical
      activity program for prostate cancer patients.
AB  - BACKGROUND: Active for Life After Cancer is a randomized trial evaluating the
      efficacy of a 6-month group-based lifestyle physical activity program (Lifestyle)
      for prostate cancer patients to improve quality of life (QOL) including physical
      and emotional functioning compared to a group-based Educational Support Program
      and a Standard Care Program (no group). METHOD: A total of 134 prostate cancer
      patients receiving continuous androgen-ablation were randomly assigned to one of
      the three study conditions. RESULTS: Results indicated no significant
      improvements in QOL at 6 or 12 months. Both group-based programs were positively
      received and yielded good attendance and retention. Lifestyle participants
      demonstrated significant improvements in most theoretical mediators proposed by
      the Transtheoretical Model and Social Cognitive Theory to affect physical
      activity. Despite these improvements, no significant changes were found for most
      physical activity measures. CONCLUSIONS: Results suggest a lifestyle program
      focusing on cognitive-behavioral skills training alone is insufficient for
      promoting routine physical activity in these patients.

PMID- 16447307
TI  - Solution-phase deuterium/hydrogen exchange at a specific residue using nozzle
      skimmer and electron capture dissociation mass spectrometry.
AB  - Information about protein conformation can be obtained with hydrogen/deuterium
      exchange (HDX) mass spectrometry. The isotopic solution-phase exchange of
      specific amide hydrogen atoms can be followed using low-vacuum nozzle-skimmer
      collision-induced dissociation (CID). In this study, the nozzle-skimmer technique
      was complemented by electron capture dissociation (ECD) Fourier transform ion
      cyclotron resonance mass spectrometry (FTICRMS). The solution-phase exchange at a
      specific residue is monitored by comparing isotopic distributions of two
      consecutive b- or c-type ions. While nozzle-skimmer fragmentation takes place in
      the low-vacuum region of the mass spectrometer, ECD occurs at ultra-high vacuum
      within the mass analyzer cell of the FTICR mass spectrometer. The dissociations
      take place at 10(-4) and 10(-9) mbar, respectively. Low-vacuum nozzle-skimmer
      fragmentation can result in intramolecular exchange between product ions and
      solvent molecules in the gas phase. Consequently, the solution-phase information
      about protein or peptide conformation is lost. It was not possible to monitor
      isotopic solution-phase exchange at the eighth residue in substance P, (Phe)8,
      with nozzle-skimmer CID. By using the in-cell ECD fragmentation method, the
      solution-phase exchange at the (Phe)8 residue was preserved during mass
      spectrometric analysis. This result shows the complementary aspects of applying
      fragmentation at low and at high vacuum, when studying isotopic exchange in
      solution at specific residues using FTICRMS.

PMID- 16447308
TI  - Cash boost for avian influenza exceeds expectations.

PMID- 16447309
TI  - Can car manufacturing techniques reform health care?

PMID- 16447310
TI  - Retrial ordered for health workers imprisoned in Libya.

PMID- 16447311
TI  - LifePoint grapples with acquisition. Woes at Province contribute to earnings
      shortfall.

PMID- 16447312
TI  - FDA OKs two new uses for biologic arthritis drug adalimumab.

PMID- 16447313
TI  - Inflammation unveiled: five new studies pave the way. Researchers are zeroing in
      on the complex role inflammation plays in many diseases and disorders.

PMID- 16447314
TI  - Supplement may ease pain of knee osteoarthritis.

PMID- 16447315
TI  - A new antidote for depression. When antidepressants and over-the-counter
      supplements don't work, this implantable device might.

PMID- 16447316
TI  - Depression may hasten heart failure.

PMID- 16447317
TI  - Aspirin: still a miracle drug after all these years. This tried-and-true heart
      medication outperforms many newer ones.

PMID- 16447318
TI  - Blood thinner cuts risk of bleeding in half.

PMID- 16447319
TI  - Fighting cancer at the grocery store. Research shows broccoli sprouts, cabbage,
      garlic, among other vegetables, contain anti-cancer properties.

PMID- 16447320
TI  - Exercise reduces long-term risk of falls.

PMID- 16447321
TI  - Increased radiation inhibits recurrence of prostate cancer. Ultimate survival
      rate of conventional and increased radiation groups remained about even, or at
      least in the short run.

PMID- 16447322
TI  - Stress could lower breast cancer risk.

PMID- 16447323
TI  - The "new" collagen: potential medical uses may abound. This protein may be
      altered to create products for oral surgery, treating burns, and stem cell
      production.

PMID- 16447325
TI  - What are the common cancers in men, and is the pattern different from that of
      women?

PMID- 16447324
TI  - Laparoscopic gallbladder surgery easier on patients.

PMID- 16447326
TI  - The WHO technique for intramuscular thigh vaccination in infants and toddlers had
      fewer adverse reactions than 2 other techniques.

PMID- 16447327
TI  - A multitude of pressures on emergency departments could limit access to care and
      raise costs even faster.

PMID- 16447328
TI  - IOM report recommends 'survivorship care plan' to guide growing number of
      Americans living with cancer.

PMID- 16447329
TI  - [Cardiac rehabilitation in the elderly].
AB  - Cardiac rehabilitation is an integral component of secondary prevention, and is
      indicated for patients with a wide variety of cardiac conditions, ranging from
      coronary artery disease to chronic heart failure. Best results are obtained with
      integrated, multicomponent cardiac rehabilitation programs, which include
      exercise training together with counseling and psychosocial measures that may
      help patients maintain sustained changes toward a more healthy lifestyle.
      Evidence from randomized controlled trials and meta-analyses supports the
      efficacy of cardiac rehabilitation on clinically relevant outcomes such as
      reduced long-term morbidity and mortality, enhanced functional profile and
      improved control of cardiovascular risk factors. However, the vast majority of
      this evidence derives from trials with only small numbers of patients > 70 years
      of age. In elderly patients the goal of cardiac rehabilitation may differ from
      those of younger patients, and include the preservation of mobility, self
      sufficiency and mental function. Cardiac rehabilitation my represent an
      opportunity to provide effective health care and achieve a high quality of life
      for older patients. Future research programs should therefore be aimed at
      specifically investigating the efficacy and effectiveness of cardiac
      rehabilitation in older, frail cardiac patients.

PMID- 16447330
TI  - [Protocol application as an understandable format and systematic elevated
      experiences].

PMID- 16447331
TI  - Open letter to the editor of The Lancet.

PMID- 16447332
TI  - Nursing praxis and the science of the unique.

PMID- 16447333
TI  - Proceedings of the First Annual Clinical Diabetes Technology Meeting. April 15
      16, 2005. San Francisco, California, USA.

PMID- 16447334
TI  - Causes of death in a rural south-west Lancashire community in the late eighteenth
      century.

PMID- 16447335
TI  - On the frontier of The Empire of Chance: statistics, accidents, and risk in
      industrializing America.
AB  - In The Empire of Chance, historians of science Gigerenzer et al. argue that
      statistical thinking has been "second to no other area of scientific endeavor" in
      its influence on "modern life and thought" (Gigerenzer et al. 1989, xiv-xv). This
      article describes how quantitative descriptions of risk associated with
      industrialization and technological change became part of the mentality of
      ordinary Americans. It explains why American began counting accidents, tells what
      kinds of accidents they counted and how they counted them, and shows how
      statistical representations of risk were used to justify prescriptions for public
      policy and individual behavior. On this frontier of the empire of chance, safety
      experts and self-styled "practical statisticians" were the principal colonizers.
      Distant from the centers of academic statistical science, they compromised
      rigorous scientific standards of methodology and accurate prediction in order to
      make convincing arguments outside their circles of expertise. To convey their
      point of view to audiences who were not literate in the field of statistics, they
      created a public language that conveyed statistical ideas through metaphors,
      graphic representations, and other rhetorical devices. They also engaged non
      experts in collecting and analyzing data and, by the 1920s, even used
      quantitative self-measurement as a device to convince members of the public to
      alter their own risk-taking behaviors.

PMID- 16447337
TI  - [Abstracts of the 50th annual meeting of the Argentine Society of Clinical
      Investigation, 2005, Mar del Plata, Argentina].

PMID- 16447336
TI  - An eighteenth-century medical-meteorological society in the Netherlands: an
      investigation of early organization, instrumentation and quantification. Part 1.
AB  - In many areas of the eighteenth century was a starting point for the
      quantification of science. It was a period in which the mania for collecting led
      to the first attempts in systematization and classification. This penchant for
      collecting was not limited to natural history specimens or curiosities. Due in
      part to the development of mathematical and physical instruments, which became
      more widely available, scholars were confronted with the informative value of
      numbers. On the one hand, sequences of measurements appeared to be the key to the
      advancement of scientific knowledge, yet on the other hand the mathematical
      apparatus to deal with these data was still largely lacking. As a result of this
      the first meteorological networks organized in the eighteenth century all became
      bogged down in the large amount of information that was collected but could not
      be processed properly. This development is illustrated in a case study of an
      early Dutch meteorological society, the Natuur-en Geneeskundige Correspondentie
      Societeit (1779-1802). What were the factors that triggered this interest in the
      weather in the Netherlands? What were the goals and expectations of the
      contributors? What were their methodological strategies? Which instruments were
      used to measure which meteorological parameters? How was the stream of numbers
      generated by these measurements organized, collected and interpreted? An analysis
      of this process reveals that limits on the advancement of meteorology were not
      only imposed by eighteenth-century Dutch Republic and the lack of a proper
      theoretical insight were also crucial factors that eventually frustrated the
      breakthrough of meteorology as an academic science in the Netherlands. This
      breakthrough was only achieved in the second half of the nineteenth century.

PMID- 16447338
TI  - Chemistry and commerce: F.B. Power and the Wellcome Chemical Research
      Laboratories.

PMID- 16447339
TI  - Louis Lotz (1843-1923) and the 'Deutsche Apotheke' in Milwaukee.

PMID- 16447340
TI  - An insight into the practice of pharmacy in ancient Egypt.

PMID- 16447341
TI  - The Trading with the Enemy Act of 1917 and synthetic drugs: relieving scarcity,
      controlling prices, and establishing pre-market licensing controls.
AB  - The "Trading with the Enemy Act" (TWEA) was enacted in October 1917 after
      America's entry into World War I and during a period of wartime scarcity and
      rising prices of synthetic drugs and dyestuffs that began in 1914. It was
      described as "An Act to define, regulate, and punish trading with the enemy, and
      for other purposes." The act and subsequent executive orders authorized an "Alien
      Property Custodian" to take control of all enemy property within the United
      States. Also, The Federal Trade Commission (FTC) was authorized to issue licenses
      for the use of enemy owned patents, which covered a range of industrial and
      consumer products. Significantly, the FTC was given the power to set the
      conditions for use of the patents and to fix the price for those products
      necessary for health. The effect of these measures was to bring federal pre
      marketing control over the production, testing, and pricing of the most
      therapeutically significant synthetic drugs of the day. Enactment of the TWEA and
      the events preceding and surrounding it are significant parts of the history of
      the American pharmaceutical industry and federal regulation.

PMID- 16447342
TI  - The pharmacist and VD control in World War II America.

PMID- 16447343
TI  - 2005 North Carolina Child Health Report Card.

PMID- 16447345
TI  - [Abstracts of the 34th Medical Congress of Maghreb, Tunisia, 15-17 December
      2005].

PMID- 16447344
TI  - The excoriation of Benjamin Bell: who was 'Jonathan Dawplucker'?
AB  - Because of a perceived lack of continuity of care of the surgical patients in
      Edinburgh Royal Infirmary, James Gregory, one of its managers, suggested that
      from 1800 a total of only six surgeons should be appointed full-time to that
      institution. As considerable animosity existed between Gregory and John Bell, a
      senior Edinburgh teacher and surgeon, a pamphlet that was extremely hostile to
      his activities was posted in prominent locations throughout Edinburgh. While the
      author was named 'Jonathan Dawplucker' it was speculated that Gregory, or one of
      his close associates, was its real author. The contents of a second Dawplucker
      pamphlet, in the same style, but probably written by John Bell, was subsequently
      published. This was extremely hostile to Benjamin Bell, one of Gregory's close
      surgical colleagues. While much distress was caused at the time, the real authors
      of these pamphlets are unlikely ever to be established.

PMID- 16447346
TI  - Before the welfare state: Bastian's Civil List pension.
AB  - Bastian, an eminent, if controversial, naturalist, pioneer neurologist, and for
      30 years, professor at University College, London, ended with a certain income of
      only L75 in his last year. Sir James Crichton-Browne initiated the grant of a
      Civil List pension. Prime Minister H Asquith, after consulting the London Royal
      Society, advised King George V to disburse a pension of L150.

PMID- 16447347
TI  - Per rectum: a history of enemata.
AB  - Enemas and clysters have been administered since before recorded history, using
      instruments ranging from cow horns and hollowed out bamboo shoots to metal
      syringes to inject laxatives, herbs, opium, turpentine, tobacco, oxygen and
      noxious chemicals. The potentially lethal dangers are today well recognised. The
      rectal route, now less often used for laxative enemas is still proving useful for
      other medications, increasingly in suppository form.

PMID- 16447348
TI  - Illness in literature: an example of Middle Scots.
AB  - Few poets have written on medical topics, but one who did was William Dunbar, an
      eighteenth century Scots poet who wrote of his headache. His headache was severe
      enough to confine him to his house, and may have been migraine, but this remains
      uncertain. Scotland's king at that time was James IV who was well-educated and
      interested in medicine. He awarded Dunbar a salary, probably as secretary in his
      household, which may reflect his general support for education and the arts.

PMID- 16447349
TI  - [Brazilian Researchers on Alzheimer's Disease and Related Disorders Meeting,
      November 25-26, 2005, Ribeirao Preto, Brasil. Abstracts].

PMID- 16447350
TI  - [Abstracts of the Berlin-Brandenburg Society of Ophthalmology meeting, 2-3
      December 2005, Berlin, Germany].

PMID- 16447352
TI  - [Review and choice for gastric cancer expanded operation or gastric cancer shrink
      operation].

PMID- 16447351
TI  - [Improve level of diagnosis treatment and academic research of gastric cancer in
      China].

PMID- 16447353
TI  - Getting ready for certification: male infertility.

PMID- 16447354
TI  - Update: Influenza activity--United States, January 8-14, 2006.

PMID- 16447356
TI  - I am doing reversed-phase high-performance liquid chromatography. What is the
      artifact peak and why does it appear?

PMID- 16447355
TI  - Attitudes of breast cancer professionals to conventional and telemedicine
      delivered multidisciplinary breast meetings.
AB  - We surveyed the attitudes of breast cancer professionals to standard face-to-face
      and future telemedicine-delivered breast multidisciplinary team (MDT) meetings.
      Interviews, which included the Group Behaviour Inventory, were conducted face-to
      face (n = 19) or by telephone (n = 26). The mean total score on the Group
      Behaviour Inventory was 96 (SD 19) for 33 respondents, which indicated
      satisfaction with standard MDT meetings, irrespective of role and base hospital.
      Positive attitudes to videoconferencing were more common among participants with
      previous experience of telemedicine (Spearman's rank correlation 0.26, P = 0.91).
      Common themes emerging from the interviews about telemedicine-delivered MDTs
      included group leadership, meeting efficiency, group interaction, group
      atmosphere and technical quality of communication. Most participants were
      satisfied with standard breast MDTs. Nurses and allied health professionals were
      least supportive of telemedicine.

PMID- 16447357
TI  - R.I. hospital, execs indicted. Charges allege bribes were paid to state lawmaker.

PMID- 16447358
TI  - What really matters most. Care for uninsured, reimbursement payments and staffing
      rank high on hospital CEOs lists of key healthcare issues, says the ACHE.
AB  - When the ACHE asked what pressing problems they were facing, hospital CEOs had a
      common refrain: money. Staffing shortages and care for the uninsured were also
      top concerns. Funding for Medicare and Medicaid is especially worrisome, given
      the current budget problems in Washington. "There's no way to know what's going
      to happen in 2006," says hospital President Joe Hodges, left.

PMID- 16447360
TI  - MedCath partners with system. Loan from Texas system to help pay hospital's debt.

PMID- 16447361
TI  - Stable outlook, for now. Fitch sees calm prospects for 2006, uncertain for 2007.

PMID- 16447359
TI  - Healing a rift? Survey aims to aid provider, intermediary relations.

PMID- 16447363
TI  - Aiming for transparency. GPO association pushes suppliers off board to lure new
      members.

PMID- 16447362
TI  - Growing pains. Merger leaves two reprocessors to withstand congressional
      scrutiny.

PMID- 16447364
TI  - A fall from grace. Cleveland clinic's ethical lapses put spotlight on healthcare
      conflicts of interest.

PMID- 16447365
TI  - Climbing the Hill. Congress set to take up healthcare issues with backdrop of
      looming midterm elections, budgetary pressures.

PMID- 16447366
TI  - Help from India Inc. For-profit enterprises train nurses headed abroad.

PMID- 16447367
TI  - A brief history of decision making.
AB  - Sometime around the middle of the past century, telephone executive Chester
      Barnard imported the term decision making from public administration into the
      business world. There it began to replace narrower terms, like "resource
      allocation" and "policy making," shifting the way managers thought about their
      role from continuous, Hamlet-like deliberation toward a crisp series of
      conclusions reached and actions taken. Yet, decision making is, of course, a
      broad and ancient human pursuit, flowing back to a time when people sought
      guidance from the stars. From those earliest days, we have strived to invent
      better tools for the purpose, from the Hindu-Arabic systems for numbering and
      algebra, to Aristotle's systematic empiricism, to friar Occam's advances in
      logic, to Francis Bacon's inductive reasoning, to Descartes's application of the
      scientific method. A growing sophistication with managing risk, along with a
      nuanced understanding of human behavior and advances in technology that support
      and mimic cognitive processes, has improved decision making in many situations.
      Even so, the history of decision-making strategies--captured in this time line
      and examined in the four accompanying essays on risk, group dynamics, technology,
      and instinct--has not marched steadily toward perfect rationalism. Twentieth
      century theorists showed that the costs of acquiring information lead executives
      to make do with only good-enough decisions. Worse, people decide against their
      own economic interests even when they know better. And in the absence of emotion,
      it's impossible to make any decisions at all. Erroneous framing, bounded
      awareness, excessive optimism: The debunking of Descartes's rational man
      threatens to swamp our confidence in our choices. Is it really surprising, then,
      that even as technology dramatically increases our access to information, Malcolm
      Gladwell extols the virtues of gut decisions made, literally, in the blink of an
      eye?

PMID- 16447368
TI  - Decisions and desire.
AB  - When we make decisions, we're not always in charge. One moment we hotheadedly let
      our emotions get the better of us; the next, we're paralyzed by uncertainty. Then
      we'll pull a brilliant decision out of thin air--and wonder how we did it. Though
      we may have no idea how decision making happens, neuroscientists peering deep
      into our brains are beginning to get the picture. What they're finding may not be
      what you want to hear, but it's worth listening. We have dog brains, basically,
      with human cortexes stuck on top. By watching the brain in action as it
      deliberates and decides, neuroscientists are finding that not a second goes by
      that our animal brains aren't conferring with our modern cortexes to influence
      their choices. Scientists have discovered, for example, that the "reward"
      circuits in the brain that activate in response to cocaine, chocolate, sex, and
      music also find pleasure in the mere anticipation of making money--or getting
      revenge. And the "aversion" circuits that react to the threat of physical pain
      also respond with disgust when we feel cheated by a partner. In this article, HBR
      senior editor Gardiner Morse describes the experiments that illuminate the
      aggressive participation of our emotion-driven animal brains in decision making.
      This research also shows that our emotional brains needn't always operate beneath
      our radar. While our dog brains sometimes hijack our higher cognitive functions
      to drive bad, or at least illogical, decisions, they play an important part in
      rational decision making as well. The more we understand about how we make
      decisions, the better we can manage them.

PMID- 16447369
TI  - Who has the D? How clear decision roles enhance organizational performance.
AB  - Decisions are the coin of the realm in business. But even in highly respected
      companies, decisions can get stuck inside the organization like loose change. As
      a result, the entire decision-making process can stall, usually at one of four
      bottlenecks: global versus local, center versus business unit, function versus
      function, and inside versus outside partners. Decision-making bottlenecks can
      occur whenever there is ambiguity or tension over who gets to decide what. For
      example, do marketers or product developers get to decide the features of a new
      product? Should a major capital investment depend on the approval of the business
      unit that will own it, or should headquarters make the final call? Which
      decisions can be delegated to an outsourcing partner, and which must be made
      internally? Bain consultants Paul Rogers and Marcia Blenko use an approach called
      RAPID (recommend, agree, perform, input, and decide) to help companies unclog
      their decision-making bottlenecks by explicitly defining roles and
      responsibilities. For example, British American Tobacco struck a new balance
      between global and local decision making to take advantage of the company's scale
      while maintaining its agility in local markets. At Wyeth Pharmaceuticals, a
      growth opportunity revealed the need to push more decisions down to the business
      units. And at the UK department-store chain John Lewis, buyers and sales staff
      clarified their decision roles in order to implement a new strategy for selling
      its salt and pepper mills. When revamping its decision-making process, a company
      must take some practical steps: Align decision roles with the most important
      sources of value, make sure that decisions are made by the right people at the
      right levels of the organization, and let the people who will live with the new
      process help design it.

PMID- 16447370
TI  - Evidence-based management.
AB  - For the most part, managers looking to cure their organizational ills rely on
      obsolete knowledge they picked up in school, long-standing but never proven
      traditions, patterns gleaned from experience, methods they happen to be skilled
      in applying, and information from vendors. They could learn a thing or two from
      practitioners of evidence-based medicine, a movement that has taken the medical
      establishment by storm over the past decade. A growing number of physicians are
      eschewing the usual, flawed resources and are instead identifying, disseminating,
      and applying research that is soundly conducted and clinically relevant. It's
      time for managers to do the same. The challenge is, quite simply, to ground
      decisions in the latest and best knowledge of what actually works. In some ways,
      that's more difficult to do in business than in medicine. The evidence is weaker
      in business; almost anyone can (and many people do) claim to be a management
      expert; and a motley crew of sources--Shakespeare, Billy Graham,Jack Welch,
      Attila the Hunare used to generate management advice. Still, it makes sense that
      when managers act on better logic and strong evidence, their companies will beat
      the competition. Like medicine, management is learned through practice and
      experience. Yet managers (like doctors) can practice their craft more effectively
      if they relentlessly seek new knowledge and insight, from both inside and outside
      their companies, so they can keep updating their assumptions, skills, and
      knowledge.

PMID- 16447371
TI  - Stop making plans; start making decisions.
AB  - Many executives have grown skeptical of strategic planning. Is it any wonder?
      Despite all the time and energy that go into it, strategic planning most often
      acts as a barrier to good decision making and does little to influence strategy.
      Strategic planning fails because of two factors: It typically occurs annually,
      and it focuses on individual business units. As such, the process is completely
      at odds with the way executives actually make important strategy decisions, which
      are neither constrained by the calendar nor defined by unit boundaries. Thus,
      according to a survey of 156 large companies, senior executives often make
      strategic decisions outside the planning process, in an ad hoc fashion and
      without rigorous analysis or productive debate. But companies can fix the process
      if they attack its root problems. A few forward-looking firms have thrown out
      their calendar-driven, business-unit-focused planning procedures and replaced
      them with continuous, issues-focused decision making. In doing so, they rely on
      several basic principles: They separate, but integrate, decision making and plan
      making. They focus on a few key themes. And they structure strategy reviews to
      produce real decisions. When companies change the timing and focus of strategic
      planning, they also change the nature of senior management's discussions about
      strategy--from "review and approve" to "debate and decide," in which top
      executives actively think through every major decision and its implications for
      the company's performance and value. The authors have found that these companies
      make more than twice as many important strategic decisions per year as companies
      that follow the traditional planning model.

PMID- 16447372
TI  - Decisions without blinders.
AB  - By the time Merck withdrew its pain relief drug Vioxx from the market in 2004,
      more than 100 million prescriptions had been filled in the United States alone.
      Yet researchers now estimate that Vioxx may have been associated with as many as
      25,000 heart attacks and strokes. Evidence of the drug's risks was available as
      early as 2000, so why did so many doctors keep prescribing it? The answer, say
      the authors, involves the phenomenon of bounded awareness--when cognitive
      blinders prevent a person from seeing, seeking, using, or sharing highly
      relevant, easily accessible, and readily perceivable information during the
      decision-making process. Doctors prescribing Vioxx, for instance, more often than
      not received positive feedback from patients. So, despite having access to
      information about the risks, physicians may have been blinded to the actual
      extent of the risks. Bounded awareness can occur at three points in the decision
      making process. First, executives may fail to see or seek out the important
      information needed to make a sound decision. Second, they may fail to use the
      information that they do see because they aren't aware of its relevance. Third,
      executives may fail to share information with others, thereby bounding the
      organization's awareness. Drawing on examples such as the Challenger disaster and
      Citibank's failures in Japan, this article examines what prevents executives from
      seeing what's right in front of them and offers advice on how to increase
      awareness. Of course, not every decision requires executives to consciously
      broaden their focus. Collecting too much information for every decision would
      waste time and other valuable resources. The key is being mindful. If executives
      think an error could generate almost irrecoverable damage, then they should
      insist on getting all the information they need to make a wise decision.

PMID- 16447373
TI  - Competing on analytics.
AB  - We all know the power of the killer app. It's not just a support tool; it's a
      strategic weapon. Companies questing for killer apps generally focus all their
      firepower on the one area that promises to create the greatest competitive
      advantage. But a new breed of organization has upped the stakes: Amazon,
      Harrah's, Capital One, and the Boston Red Sox have all dominated their fields by
      deploying industrial-strength analytics across a wide variety of activities. At a
      time when firms in many industries offer similar products and use comparable
      technologies, business processes are among the few remaining points of
      differentiation--and analytics competitors wring every last drop of value from
      those processes. Employees hired for their expertise with numbers or trained to
      recognize their importance are armed with the best evidence and the best
      quantitative tools. As a result, they make the best decisions. In companies that
      compete on analytics, senior executives make it clear--from the top down--that
      analytics is central to strategy. Such organizations launch multiple initiatives
      involving complex data and statistical analysis, and quantitative activity is
      managed atthe enterprise (not departmental) level. In this article, professor
      Thomas H. Davenport lays out the characteristics and practices of these
      statistical masters and describes some of the very substantial changes other
      companies must undergo in order to compete on quantitative turf. As one would
      expect, the transformation requires a significant investment in technology, the
      accumulation of massive stores of data, and the formulation of company-wide
      strategies for managing the data. But, at least as important, it also requires
      executives' vocal, unswerving commitment and willingness to change the way
      employees think, work, and are treated.

PMID- 16447374
TI  - An introduction to Bayesian hierarchical models with an application in the theory
      of signal detection.
AB  - Although many nonlinear models of cognition have been proposed in the past 50
      years, there has been little consideration of corresponding statistical
      techniques for their analysis. In analyses with nonlinear models, unmodeled
      variability from the selection of items or participants may lead to
      asymptotically biased estimation. This asymptotic bias, in turn, renders
      inference problematic. We show, for example, that a signal detection analysis of
      recognition memory data leads to asymptotic underestimation of sensitivity. To
      eliminate asymptotic bias, we advocate hierarchical models in which participant
      variability, item variability, and measurement error are modeled simultaneously.
      By accounting for multiple sources of variability, hierarchical models yield
      consistent and accurate estimates of participant and item effects in recognition
      memory. This article is written in tutorial format; we provide an introduction to
      Bayesian statistics, hierarchical modeling, and Markov chain Monte Carlo
      computational techniques.

PMID- 16447375
TI  - Modeling individual differences in cognition.
AB  - Many evaluations of cognitive models rely on data that have been averaged or
      aggregated across all experimental subjects, and so fail to consider the
      possibility of important individual differences between subjects. Other
      evaluations are done at the single-subject level, and so fail to benefit from the
      reduction of noise that data averaging or aggregation potentially provides. To
      overcome these weaknesses, we have developed a general approach to modeling
      individual differences using families of cognitive models in which different
      groups of subjects are identified as having different psychological behavior.
      Separate models with separate parameterizations are applied to each group of
      subjects, and Bayesian model selection is used to determine the appropriate
      number of groups. We evaluate this individual differences approach in a
      simulation study and show that it is superior in terms of the key modeling goals
      of prediction and understanding. We also provide two practical demonstrations of
      the approach, one using the ALCOVE model of category learning with data from four
      previously analyzed category learning experiments, the other using
      multidimensional scaling representational models with previously analyzed
      similarity data for colors. In both demonstrations, meaningful individual
      differences are found and the psychological models are able to account for this
      variation through interpretable differences in parameterization. The results
      highlight the potential of extending cognitive models to consider individual
      differences.

PMID- 16447376
TI  - Basic processes in reading: a critical review of pseudohomophone effects in
      reading aloud and a new computational account.
AB  - There are pervasive lexical influences on the time that it takes to read aloud
      novel letter strings that sound like real words (e.g., brane from brain).
      However, the literature presents a complicated picture, given that the time taken
      to read aloud such items is sometimes shorter and sometimes longer than a control
      string (e.g.,frane) and that the time to read aloud is sometimes affected by the
      frequency of the base word and other times is not. In the present review, we
      first organize these data to show that there is considerably more consistency
      than has previously been acknowledged. We then consider six different accounts
      that have been proposed to explain various aspects of these data. Four of them
      immediately fail in one way or another. The remaining two accounts may be able to
      explain these findings, but they either make counterintuitive assumptions or
      invoke a novel mechanism solely to explain these findings. A new account is
      advanced that is able to explain all of the effects reviewed here and has none of
      the problems associated with the other accounts. According to this account,
      different types of lexical knowledge are used when pseudohomophones and nonword
      controls are read aloud in mixed and pure lists. This account is then implemented
      in Coltheart, Rastle, Perry, Langdon, and Ziegler's (2001) dual route cascaded
      model in order to provide an existence proof that it accommodates all of the
      effects, while retaining the ability to simulate three standard effects seen in
      nonword reading aloud.

PMID- 16447377
TI  - The time it takes to switch attention.
AB  - An experiment is reported that measured the time it takes to switch attention
      from one set of locations to another in response to a cue that indicates the
      relevant locations. The experiment compared sequences of trials in which the same
      locations were cued in succession with sequences in which different locations
      were cued in succession in order to separate cue-encoding time from attention
      switching time. Same-location sequences require cue encoding but not attention
      switching. They were substantially faster than different-location sequences,
      which require both cue encoding and attention switching. Formal models were
      fitted to time-course functions generated by presenting the cues 0, 100, 200,
      300, or 400 msec before the target displays. The model fits suggest that cue
      encoding took 67-74 msec and attention switching took 76-101 msec.

PMID- 16447378
TI  - Attentional rubbernecking: cognitive control and personality in emotion-induced
      blindness.
AB  - Emotional stimuli often attract attention, but at what cost to the processing of
      other stimuli? Given the potential costs, to what degree can people override
      emotion-based attentional biases? In Experiment 1, participants searched for a
      single target within a rapid serial visual presentation of pictures; an
      irrelevant, emotionally negative or neutral picture preceded the target by either
      two or eight items. At the shorter lag, negative pictures spontaneously induced
      greater deficits in target processing than neutral pictures did. Thus,
      attentional biases to emotional information induced a temporary inability to
      process stimuli that people actively sought. Experiment 2 revealed that
      participants could reduce this effect through attentional strategy, but that the
      extent of this reduction was related to their level of the personality trait harm
      avoidance. Participants lower in harm avoidance were able to reduce emotion
      induced blindness under conditions designed to facilitate the ignoring of the
      emotional stimuli. Those higher in harm avoidance were unable to do so.

PMID- 16447379
TI  - Attention capture is modulated in dual-task situations.
AB  - Because some features affect the efficiency of visual search even when they are
      irrelevant to the task, they are thought to capture attention in a stimulus
      driven manner. If such attention shifts are stimulus driven, they should be
      unaffected by reduced resources. We added a concurrent auditory task to a
      traditional attention capture paradigm and found that capture by an irrelevant,
      abruptly appearing stimulus (i.e., an onset) was eliminated. In contrast,
      prioritization of an irrelevant color singleton--a stimulus that at most receives
      only mild prioritization in this paradigm--was increased under dual-task
      conditions. These results challenge the hypothesis that attention capture by
      irrelevant features is stimulus driven. Instead, prioritization depends on and is
      modulated by the availability of resources.

PMID- 16447380
TI  - The role of working memory in attentional capture.
AB  - Much previous research has demonstrated that visual search is typically disrupted
      by the presence of a unique "singleton" distractor in the search display. Here we
      show that attentional capture by an irrelevant color singleton during shape
      search critically depends on availability of working memory to the search task:
      When working memory is loaded in a concurrent yet unrelated verbal short-term
      memory task, capture increases. These findings converge with previous
      demonstrations that increasing working memory load results in greater distractor
      interference in Stroop-like tasks (de Fockert, Rees, Frith, & Lavie, 2001; Lavie,
      Hirst, de Fockert, & Viding, 2004), which support the hypothesis that working
      memory provides goal-directed control of visual selective attention allowing to
      minimize interference by goal-irrelevant distractors.

PMID- 16447381
TI  - The role of working memory in spatial enumeration: patterns of selective
      interference in subitizing and counting.
AB  - Articulatory suppression (repeatedly pronouncing a syllable or word while
      carrying out another task) is thought to interfere selectively with the
      phonological store in working memory. Although suppression interferes with
      temporal enumeration (enumerating successive light flashes), to date there has
      been little evidence of such interference in spatial enumeration (enumerating
      units laid out in space at one time)--a finding with serious ramifications for
      theories of enumeration. Participants carried out a spatial enumeration task,
      enumerating 1-8 dots while listening to a metronome (baseline condition) or while
      carrying out a secondary task to the rhythm of the metronome (dual-task
      condition). There were four secondary tasks: simple articulation (saying a
      letter), complex articulation (alternating between two letters), simple tapping
      (tapping a finger), and complex tapping (alternating between two fingers).
      Interference varied with number of items, but the pattern differed from that
      observed with temporal enumeration.

PMID- 16447382
TI  - Response-response compatibility during bimanual movements: evidence for the
      conceptual coding of action.
AB  - The present study investigated response-response (R-R) compatibility in a
      bimanual keypressing task. Numeric and spatial stimuli were used to cue responses
      for each hand. Two groups of participants differed in terms of the stimulus
      response mappings for the numeric stimuli. For one group, the numeric stimuli
      were mapped so that the same number for each hand indicated responses that were
      anatomically compatible (e.g., index finger of both hands). For the other group,
      the same number for each hand indicated responses that were left-right compatible
      (e.g., leftmost finger of both hands). The spatial stimuli were mapped in a
      spatially compatible manner to the responses for both groups. For numeric
      stimuli, reaction times (RTs) were faster when the same number indicated the
      response for each hand, regardless of the mapping. For the spatial stimuli, RTs
      were determined not only by the pairing of stimuli or responses, but also by how
      the responses were indicated by numeric stimuli. The results indicate that R-R
      compatibility effects are mediated by abstract codes that reflect individuals'
      conceptualizations of their actions.

PMID- 16447383
TI  - Notional number agreement in English.
AB  - To investigate the contested role of notional number in English subject-verb
      agreement, we used a sentence completion task to examine agreement with minimally
      different subject noun-phrases, such as the gang on the motorcycles and the gang
      near the motorcycles. These contrasting phrases biased different notional
      construals of collective nouns, such as gang, which are normally ambiguous
      between plural (distributed) and singular (collected) construals. With subjects
      biased toward spatial distribution, such as gang on motorcycles, more plural
      verbs occurred in speakers' sentence completions than in sentence completions
      with a bias toward spatial collection, such as gang near motorcycles. This offers
      strong evidence regarding both the existence and the magnitude of notional
      effects on subject-verb number agreement in English.

PMID- 16447384
TI  - Resistance is futile: the unwitting insertion of analogical inferences in memory.
AB  - Analogical inferences can modify people's understanding, but can this occur even
      when the inferences are unpalatable? We report two experiments suggesting that
      this is the case. Participants read a source passage on the role and status of
      gay people in society. Half then read an analogy describing the historical
      persecution of left-handers. On a subsequent recognition test, the participants
      who read the analogy were more likely than the control participants to
      misrecognize analogical inferences as statements explicitly presented, but the
      two groups did not differ in recognition rates for other kinds of statements. A
      priori explicit attitudes toward gays did not moderate these findings, although
      the participants with more positive attitudes toward gays saw the analogy to left
      handers as more sound. Our findings demonstrate that analogical inferences can be
      seamlessly integrated into mental representations of the target domain even when
      those inferences are unpalatable; in short, resistance to analogy is futile.

PMID- 16447385
TI  - Using context to build semantics.
AB  - Latent semantic analysis (LSA) is a model of knowledge representation for words.
      It works by applying dimension reduction to local co-occurrence data from a large
      collection of documents after performing singular value decomposition on it. When
      the reduction is applied, the system forms condensed representations for the
      words that incorporate higher order associations. The higher order associations
      are primarily responsible for any semantic similarity between words in LSA. In
      this article, a memory model is described that creates semantic representations
      for words that are similar in form to those created by LSA. However, instead of
      applying dimension reduction, the model builds the representations by using a
      retrieval mechanism from a well-known account of episodic memory.

PMID- 16447386
TI  - What is preexisting strength? Predicting free association probabilities,
      similarity ratings, and cued recall probabilities.
AB  - Measuring lexical knowledge poses a challenge to the study of the influence of
      preexisting knowledge on the retrieval of new memories. Many tasks focus on word
      pairs, but words are embedded in associative networks, so how should preexisting
      pair strength be measured? It has been measured by free association, similarity
      ratings, and co-occurrence statistics. Researchers interpret free association
      response probabilities as unbiased estimates of forward cue-to-target strength.
      In Study 1, analyses of large free association and extralist cued recall
      databases indicate that this interpretation is incorrect. Competitor and backward
      strengths bias free association probabilities, and as with other recall tasks,
      preexisting strength is described by a ratio rule. In Study 2, associative
      similarity ratings are predicted by forward and backward, but not by competitor,
      strength. Preexisting strength is not a unitary construct, because its
      measurement varies with method. Furthermore, free association probabilities
      predict extralist cued recall better than do ratings and co-occurrence
      statistics. The measure that most closely matches the criterion task may provide
      the best estimate of the identity of preexisting strength.

PMID- 16447387
TI  - Revisiting the role of recollection in item versus forced-choice recognition
      memory.
AB  - Many memory theorists have assumed that forced-choice recognition tests can rely
      more on familiarity, whereas item (yes-no) tests must rely more on recollection.
      In actuality, several studies have found no differences in the contributions of
      recollection and familiarity underlying the two different test formats. Using
      word frequency to manipulate stimulus characteristics, the present study
      demonstrated that the contributions of recollection to item versus forced-choice
      tests is variable. Low word frequency resulted in significantly more recollection
      in an item test than did a forced-choice procedure, but high word frequency
      produced the opposite result. These results clearly constrain any uniform claim
      about the degree to which recollection supports responding in item versus forced
      choice tests.

PMID- 16447388
TI  - Speeded retrieval abolishes the false-memory suppression effect: evidence for the
      distinctiveness heuristic.
AB  - We examined two different accounts of why studying distinctive information
      reduces false memories within the DRM paradigm. The impoverished relational
      encoding account predicts that less memorial information, such as overall
      familiarity, is elicited by the critical lure after distinctive encoding than
      after nondistinctive encoding. By contrast, the distinctiveness heuristic
      predicts that participants use a deliberate retrieval strategy to withhold
      responding to the critical lures. This retrieval strategy refers to a decision
      rule whereby the absence of memory for expected distinctive information is taken
      as evidence for an event's nonoccurrence. We show that the typical false
      recognition suppression effect only occurs when the recognition test is self
      paced. This suppression effect is abolished when participants make recognition
      decisions under time pressure, such as within 1 second of seeing the test item.
      These results are consistent with the distinctiveness heuristic that a time
      consuming retrieval strategy is used to reduce false-recognition responses.

PMID- 16447389
TI  - Integrated versus segregated accounting and the magnitude effect in temporal
      discounting.
AB  - Temporal discounting rates in humans generally decrease as the amount of reward
      increases, a phenomenon known as the magnitude effect. In the present study, we
      examined whether temporal discounting and the magnitude effect are related to
      segregation of choices in terms of gains or losses for waiting for or expediting
      receipt of a reward. Subjects (N = 24) responded to a series of hypothetical
      choices about amounts of money available either immediately or after a delay. The
      immediate and delayed amounts either were presented as integrated amounts in the
      baseline condition or were segregated as differential gains or losses for
      choosing delayed or expedited consumption (delay and speedup conditions,
      respectively). Temporal discounting rates decreased in the segregated conditions,
      in accord with the standard discounted utility model but contrary to the
      hypothesis that the subjects were choosing on the basis of reward differentials
      in the baseline condition. The size of the magnitude effect was comparable in the
      baseline and the delay conditions but decreased in the speed-up condition. These
      results challenge explanations of the magnitude effect in terms of an increasing
      proportional sensitivity property of the utility function (Loewenstein & Prelec,
      1992) and the hypothesis that subjects choose on the basis of differentials even
      when the rewards are presented as integrated amounts.

PMID- 16447391
TI  - The wall inside the brain: overestimation of distances crossing the former Iron
      Curtain.
AB  - A study of distance estimations between German cities investigated the
      organization of mental maps and their specific deviations from reality. Potential
      factors for the deviation of mental maps from reality are physical barriers,
      emotional involvement, and semantic unity. Distance estimations between cities
      situated in different former parts of Germany (East or West) were systematically
      overestimated compared to distances of cities located in the same parts of
      Germany. This trend was strengthened when participants had a negative attitude
      toward the reunification of Germany. The impact of these results is far reaching,
      because overestimated distances between both German parts indicate that there
      still exists a mental gap between East and West--even in young people--15 years
      after the German reunification.

PMID- 16447390
TI  - A psychometric approach to intuitive physics.
AB  - The literature on intuitive physics shows that many people exhibit systematic
      errors when predicting the behavior of simple physical events. Most previous
      research has attributed these errors to factors specific to a certain class of
      tasks. In the present study, we investigated the possibility that intuitive
      physics performance may be related to general measures of cognitive ability. Two
      hundred four adults (ages, 20-91 years) were presented with five pairs of
      intuitive physics questions. It was found that performance on the intuitive
      physics items was moderately intercorrelated, suggesting that they were tapping
      into a unitary construct. Despite the correlation with factors that decline with
      advancing age, intuitive physics performance was not correlated with age (r =
      .00). The findings are discussed in the context of research on intuitive physics,
      as well as research on cognitive aging.

PMID- 16447392
TI  - Is size perception based on monocular distance cues computed automatically?
AB  - The study reported here examined whether size perception based on monocular
      distance cues is computed automatically. Participants were presented with a
      picture containing distance cues, which was superimposed with a pair of digits
      differing in numerical value. One digit was presented so as to be perceived as
      closer than the other. The digits were of similar physical size but differed in
      their perceptual size. The participants' task was to decide which digit was
      numerically larger. It was found that the decision took longer and resulted in
      more errors when the perceptual size of the numerically larger digit was smaller
      than the perceptual size of the numerically smaller digit. These results show
      that perceived size affects performance in a task that does not require size or
      distance computation. Hence, for the first time, there is empirical support for
      the working assumption of the visual perception approach that size perception
      based on monocular distance cues is computed automatically.

PMID- 16447393
TI  - Hemispheric asymmetry in temporal resolution: contribution of the magnocellular
      pathway.
AB  - Right-handed participants performed simple visual judgments on nonverbal stimuli
      presented either to the left visual field-right hemisphere (LVF-RH) or to the
      right visual field-left hemisphere (RVF-LH). The stimuli were exposed for 40-120
      msec, followed by a backward mask. When the stimuli were presented against a
      green background, an RVF-LH advantage was observed for the shortest exposure
      duration. This result supports the notion that the LH has finer temporal
      resolution than the RH. Imposition of a red background disrupted performance and
      eliminated the RVF-LH advantage for the shortest exposure duration. Because the
      red background attenuates functions of the magnocellular pathway, these results
      suggest that the magnocellular pathway contributes to the LH advantage for fine
      temporal resolution.

PMID- 16447394
TI  - The role of contextual cues in the haptic perception of orientations and the
      oblique effect.
AB  - Blindfolded right-handed participants were asked to position, with the right
      hand, a frontoparallel rod to one of three orientations: vertical (0 degrees) and
      left 45 degrees and right 45 degrees obliques. Simultaneously, three different
      backgrounds were explored with the left hand: smooth, congruent stripes (parallel
      to the orientation to be produced), or incongruent stripes (tilted relative to
      the orientation to be produced). The analysis of variable errors showed that the
      oblique effect (higher precision for the vertical orientation than for the
      oblique orientations) was weakened in the presence of contextual cues, because of
      an improvement in oblique precision. Moreover, the analysis of constant errors
      revealed that the perception of orientations erred in the direction of the
      stripes, similar to the effect that has been found with vision, where visual
      contextual cues (tilted frame or lines) divert the perception of the vertical.
      These results are discussed in relation to a patterncentric frame of reference
      hypothesis or as a congruency effect.

PMID- 16447395
TI  - Caring for people who are dying: implications of the Burke vs. GMC case.

PMID- 16447396
TI  - Improving outcome in Parkinson's disease.

PMID- 16447397
TI  - Imaging of the pancreas.

PMID- 16447398
TI  - Pancreatic and periampullary cancers: treatment and outcome.

PMID- 16447399
TI  - Pancreatic transplantation for patients with type 1 diabetes.

PMID- 16447400
TI  - Current concepts in diagnosis and treatment of sialolithiasis.

PMID- 16447401
TI  - Building patient confidence through effective communication.

PMID- 16447402
TI  - Intestinal obstruction.

PMID- 16447403
TI  - Interpretation of ankle and foot radiographs.

PMID- 16447404
TI  - Aspiration of the elbow joint.

PMID- 16447405
TI  - An avoidable antiarrhythmic side effect.

PMID- 16447406
TI  - Tube thoracostomy: how to insert a chest drain.

PMID- 16447407
TI  - So you want to be...a radiologist.

PMID- 16447408
TI  - Sedation for procedures in children: a guide for the non-anaesthetist.

PMID- 16447409
TI  - An evaluation of four foundation programme pilots in the Kent Surrey and Sussex
      Deanery.

PMID- 16447410
TI  - Late presentation of choanal atresia.

PMID- 16447411
TI  - Endobronchial actinomycosis: is a repeat bronchoscopy after treatment necessary?

PMID- 16447412
TI  - Spontaneous intracranial hypotension.

PMID- 16447413
TI  - Benign cystic nephroma.

PMID- 16447414
TI  - Delirium in the elderly: the importance of accurate diagnosis.

PMID- 16447415
TI  - The levonorgestrel-releasing intrauterine system for menorrhagia.

PMID- 16447416
TI  - The beginning of modern kidney transplantation.

PMID- 16447417
TI  - Protecting your lifestyle.

PMID- 16447418
TI  - Thoracic epidurals for on-pump cardiac surgery: a good or bad idea?

PMID- 16447419
TI  - [Soil respiration and its influencing factors at grazing and fenced typical
      Leymus chinensis Steppe, Nei Monggol].
AB  - Based on two-year soil respiration observing data at fenced and grazing typical
      Leymus chinensis steppe, Nei Monggol by the enclosed chamber method, soil
      respiration and its relationships with various affecting factors were analyzed.
      The major results include: (1) The diurnal and seasonal dynamics of soil
      respiration are similar at fenced and grazing typical Leymus chinensis steppe,
      but soil respiration rate is larger at the fenced plots than that at the grazing
      plots, and their values were 219.18 mg x (m2 x h)(-1) and 111.27 mg x (m2 x h)(
      1), respectively. The reason of soil respiration rate increasing in the fenced
      plots might be the increases of biomass in the belowground and soil water
      content. (2) Among the influencing factors on soil respiration, grazing decreases
      the effects of soil water content and relative humidity and increases the effect
      of photosynthetic rate, and has no significant effects on other factors. (3) At
      the fenced plots, the correlation of soil respiration rate with soil water
      content is largest, followed by photosynthetic rate, air temperature, relative
      humidity, air CO2 concentration, intercellular CO2 concentration, stomatal
      conductance and the lowest being photosynthetically active radiation. Soil water
      content and air temperature are the main environmental factors, and
      photosynthetic rate is the critical biotic factor. The affecting factors on soil
      respiration are the same at the fenced and grazing plots, however the importance
      of those influencing factors is changed quantitatively.

PMID- 16447420
TI  - [Estimation of CO2 fluxes from rice paddies based on transparent chamber
      measurement].
AB  - Closed chamber provide a valuable tool for measuring CO2 exchange fluxes. In
      general, the change rate of CO2 concentration is assumed to be constant in the
      short measurement time and a linear regression method is used to estimate the CO2
      fluxes. However, due to the physical and physiological effects, the change rate
      of CO2 is not always constant. A linear regression method and an exponential
      regression method are compared in this study. Results show that during the
      growing stages except for the ripening, nonlinear relationship of CO2
      concentration versus time was estimated in the sunny daytime. Absolute values of
      CO2 fluxes calculated by linear regression were lower than that by exponential
      regression. Whereas, CO2 concentration changed linearly with time in cloudy days
      or in nighttime. And no significant difference was found between the results
      calculated with these two methods. Accumulative CO2-C fluxes with exponential and
      linear regressions were compared with the values of net ecosystem exchange of CO2
      C (NEE), which were calculated by net primary production (NPP) minus soil
      respiration. The values with the exponential regression method were closer to NEE
      than those with linear regression. Therefore, the linear regression method could
      result in underestimation of carbon budget of ecosystem. Based on transparent
      chamber measurement, the exponential regression is more feasible to calculate CO2
      fluxes than the linear regression.

PMID- 16447421
TI  - [Reactivity of the limestone in wet flue gas desulfurization].
AB  - On the basis of the analysis of chemical components of the natural limestones
      from different deposits in China, the pore structures of the typical limestones,
      with the different CaCO3 content, were examined. The reactivity of the limestones
      was investigated by sulfuric acid titration and gas-liquid absorption methods.
      The research results showed that the specific surface area of the natural
      limestones studied in this work was about 1.8 m2/g. It was seen that the pH of
      the limestone slurry rapidly decreased and then back up when the sulfuric acid
      was added. The higher the CaCO3 content was, or the smaller the particle size
      was, the larger the pH back-up rate was, and similarly the faster the SO2
      concentration of the reactor outlet increased. The Reactivity of the limestone
      obtained by the sulfuric acid titration had the same features as that obtained by
      the gas liquid absorption. Compared with the specific surface area, the CaCO3
      content had more effect on the reactivity of the limestones. The particle size of
      the limestones had a significant effect on the reactivity when the particle size
      was relatively large, that is less than 300-360 mesh, vice versa.

PMID- 16447422
TI  - [Microbial reduction of Fe(III) (EDTA) in the system of nitric oxide removal by
      metal chelate absorption].
AB  - Reduction of Fe(III) (EDTA) with cultivated microorganisms in the system of
      nitric oxide removal by metal chelate absorption was investigated. Supplemental
      glucose stimulates the formation of Fe(II) (EDTA) more than ethanol and methanol
      as the carbon sources. Ammonium salt was used to be as the nitric source instead
      of nitrate, which inhibits the reduction of Fe(III) (EDTA) due to the competition
      between the two electron acceptors. The optimal pH value was from 6 to 7. The
      reduction percentage of Fe(III) (EDTA) varied little with the range of 30 degrees
      C - 40 degrees C and decreased quickly with a temperature higher than 40 degrees
      C. The bio-reduction could be achieved efficiently with enough carbon source and
      cell inoculation. The reduction rate did not increase with adding more amount of
      carbon source or cell inoculation. The bio-reduction rate could be described by
      Michaelis-Menten equation and fitted to the first order reaction kinetics. The
      maximum reaction rates gamma max and the Michaelis constant k(m) were 1.3 mmol x
      (L x h)(-1) and 53.5 mmol x L(-1)respectively.

PMID- 16447423
TI  - [Utilizing fereducer reaction to enhance DC corona radical shower for benzene
      treatment].
AB  - Fereducer reaction is introduced to enhance DC corona radicals shower for removal
      of benzene in air. In the presence of nozzle electrode gas containing Fereducer
      reagent, the enhanced decomposing efficiencies were 21% and 4.2% for benzene
      concentration of 953 mg/m3 and 63 mg/m3, respectively. The enhancement of benzene
      removal was remarkable in the presence of nozzle electrode gas (O2, H2O) with the
      highest removal rate of 89.6%. Lower initial concentration of benzene has higher
      removal efficiency. However, higher absolute removal rate would be achieved when
      initial concentration of benzene was higher.

PMID- 16447424
TI  - [Life cycle assessment on oxygen biofuels].
AB  - Life Cycle Assessment (LCA) was used to compare energy consumption and pollutant
      emissions of two oxygen biofuels, ethanol and methyl ester, which were mixed with
      gasoline and diesel oil at levels of 10% and 30% of the biofuel. The future of
      oxygen-containing biofuels was analyzed and forecasted. The results show that the
      mixture of biofuels and petroleum products can reduce crude oil consumption, but
      only methyl ester alternative fuel can reduce fossil fuel consumption. Use of
      methyl ester mixtures would reduce NOx by 50% compared to gasoline or diesel on a
      life cycle basis; however, NOx would increase using ethanol. Each alternative
      fuel mixture reduced PM10 emissions from the vehicle and methyl ester decreased
      VOCs. The SO2 emissions from the fuel production processes, which account for
      about 80% of SO2 life cycle emissions, must be strictly controlled.

PMID- 16447425
TI  - [Particle trajectory model desulfurization spray tower used in numerical
      simulation of flue gas].
AB  - The commercial computational fluid dynamics (CFD) software FLUENT is used to
      predict the two-phase flow in a flue gas desulfurization (FGD) spray tower. The
      Euler-Lagrange method is used, in which the gas flow is described with standard k
      epsilon turbulence model, and the motion of the liquid droplets is described with
      the particle trajectory model. The procedure of model definition, including force
      analysis of liquid particle, gas turbulent dispersion and the gas-liquid coupling
      method, is presented. The results show that the uniformity of axial gas velocity
      in the spray tower is satisfactory, and the hollow spray nozzle used in the tower
      can efficiently prevent short-circuiting of the flue gas. The concentration of
      liquid droplets in the central region is higher than near the wall, and this
      problem can be solved by optimizing the arrangement of the spray nozzles near the
      wall. Model predictions for particle trajectory are shown to be in good agreement
      with experimental results, and the particle trajectory model can predict the two
      phase flow in the spray tower successfully.

PMID- 16447426
TI  - [Relationship between organic carbon and water content in four type wetland
      sediments in Sanjiang Plain].
AB  - Characteristic and relationship were analyzed between organic carbon and water
      content in four types of wetlands (one cultivated wetland and three typical
      natural wetlands including fen, marsh and marshy meadow) in Sanjiang Plain of
      Northeastern China. Results show that there are distinct differences in the
      depths of organic carbon deposition, the organic carbon and water content in
      sediment profiles of these four type wetlands. There are significant positive
      correlations between organic carbon and water content in sediment profiles of the
      same type wetland (p < 0.01; R2 = 0.8276, 0.9917, 0.9916 and 0.9782 for
      cultivated wetland, fen, marsh and marshy meadow, respectively). The trend for
      evolution of ecological and environmental functions of wetland ecosystems is
      discussed based on the analysis of the relationship between soil organic carbon
      and water content. The results further illustrate the viewpoint that the
      protection and restoration of wetlands could lessen the global climate change
      caused by the increase in atmospheric CO2 concentration.

PMID- 16447427
TI  - [Impact of macrofaunal activities on the DIN exchange at the sediment-water
      interface along the tidal flat of Yangtze River estuary].
AB  - The macrofaunal activities exert intensive and extensive influences on the
      accumulation, transportation, exchange and geochemistry processes of pollutants
      and redox sensitive elements around the sediment-water interface. Based on the
      simulated and contrastive analysis method, effects of bivalve Corbicula fluminea
      activities on dissolved inorganic nitrogen (DIN) exchange between sediment-water
      interface in different experimental conditions and nitrogen biogeochemical
      cycling along the tidal flats of Yangtze River estuary are discussed. In short
      time experiment, Corbicula fluminea burrowing activities increased NH4+ release
      from sediments, and NO3- efflux to overlying water was much more in Corbicula
      fluminea inhabiting core. During long time incubation, NH4- and N released in
      turn from the sediments, bioturation can facilitate NH4- release from the
      sediments at the beginning of incubation, and stronger nmistrification derived
      from bioturbation witin the sediments enlarge Nsedim concentration. Disturbance
      and bioirrigation of Corbicula flumuminea can accelerate organic matter
      mineralization and N(DIN) exchange between overlying water and pore water, result
      in a larger release from NH4+ pool in top-sediment to overlying water. In
      conclusion, by means of excretion, burrowing, bioirrigation and biotuary ation,
      Corbicula fluuminea burrowing activities can evidently modify the nitrogen
      dynamics in sediment-water system.

PMID- 16447428
TI  - [Analysizing and quantitatively evaluating the organic matter source at different
      ecologic zones of tidal salt marsh, North Jiangsu Province].
AB  - The indicators including TOC, TN, C/N, delta 13C and delta 15N of surface
      sediments, core sediments and plants of tidal salt marshes in North Jiangsu
      Province are analysized.Subsequently, distribution regularities of these
      measurement indicators are discussed, and the biogeochemistry processes between
      sediments and plants are also analysized. Lastly, the organic matter sources of
      different ecologic zones in tidal salt marsh are evaluated, and the organic
      matter accumulations in different ecologic zones induced by their plants are also
      compared. The results indicate that TOC, TN, C/N and delta 13C show obviously
      zonal distribution. The organic matter sources are dominated by marine input in
      silt flat, Artemisia schrenkiana flat, and the transition zone between silt and
      Spartina alterniflora flat, and controlled by terrigenous input in Spartina
      alterniflora flat. Spartina alterniflora plays an important role in the
      accumulation of organic matter in the whole tidal salt marshes ecosystem. In
      study area, the annually increased TOC, organic matter and TN in Spartina
      alterniflora flat, Artemisia schrenkiana flat and reed flat respectively reach 6
      451t, 16 595t and 536t. The amount of TOC, organic matter and TN accumulated in
      Spartina alterniflora flat are more than those in other ecological zones, which
      show that the Spartina alterniflora flat exert nonreplaceable effect on the
      material cycle and exchange in the whole tidal salt marshes ecosystem.

PMID- 16447429
TI  - [Importation of wind-driven drift of mat-like algae bloom into Meiliang Bay of
      Taihu Lake in 2004 summer].
AB  - Driven by the prevailing south wind in summer, floating mat-like algal blooms in
      the open area of Taihu Lake would drift into Meiliang Bay located in the northern
      part of Taihu Lake. An exponential relationship between wind speed and algal
      drift velocity was found through controlled flume experiments and field
      observations. Then the relationship was applied to compute drift importation into
      Meiliang Bay in six dates when mat-like algal blooms were happening. During the
      six dates, except on 2004-07-31 the algal boom drifted outwards from Meiliang Bay
      with slight amounts of 0.05 km2; for the rest of dates, the importations were
      inwards positive, the maximum importation occurred on 2004-06-11, being 17.4 km2,
      and the minimum importation on 2004-07-30, being 4.8 km2; The results indicated
      importation of wind-driven algae drift during 24 hours accounts for 3.7% - 13.3%
      of the area of Meiliang Bay.

PMID- 16447430
TI  - [Study on the groundwater petroleum contaminant biodegradation by high efficient
      microorganism].
AB  - The groundwater petroleum contaminant biodegradation effect by high efficient
      hybrid microorganism was. investigated and the groundwater contaminant
      biodegradation transportation mathematical model was established in this study.
      The high efficient bacteria was separated and filtrated from the soil
      contaminated by petroleum hydrocarbon, and it was identified as Pseudomonas,
      Flavobacterium and Micrococcus. The petroleum degradation rates by these three
      kinds microorganism were 62%, 56% and 62% respectively in 24 h, and the high
      petroleum biodegradation rate 85% could be achieved by the hybrid microorganism
      constituted by these three kinds of microorganism, which was higher than that of
      any other each single bacteria community. The hybrid microorganism in-flowed into
      the reactor imitating the aquifer media with the petroleum wastewater, and it
      could form a steady microorganism zone in the foreside of the reactor. The
      petroleum biodegradation rate could achieve 60% when the petroleum wastewater
      flowed through this microorganism zone and the average petroleum biodegradation
      rate could reach up to 90% in the effluent. The groundwater contaminant
      biodegradation transportation mathematical model can predict the biodegradation
      of the wastewater through the microorganism zone effectively, of which the
      calculating values have good relativity with those of measurement.

PMID- 16447431
TI  - [Studies on the performance of bioferric-SMBR].
AB  - To enhance removal efficiency and to mitigate membrane fouling, submerged
      membrane bioreactor and Bioferric process are combined to Bioferric-SMBR.
      Parallel compared experiment of Bioferric-SMBR and common SMBR dealing with
      dyeing wastewater was carried out. Bioferric-SMBR show great superiority and can
      enhance removal efficiency, reduce membrane fouling and improve sludge
      characteristic. When volume load rate is 25% higher than that of common SMBR, the
      removal efficiency of Bioferric-SMBR on COD, chroma and NH3-N is 1.0%, 9.5% and
      5.2% higher than that of the latter respectively. The trans-membrane pressure of
      Bioferric-SMBR is just only 36% of that in common SMBR while it's membrane flux
      is 25% higher than that of common SMBR. It's stably running day is 2.5 folds of
      which in common SMBR when there is no surplus sludge discharged. The MLSS
      concentration of Bioferric-SMBR is higher than that of the latter with more
      different kinds microorganism such as protozoan, metazoan, etc. It's mean
      particle diameter value and sludge oxygen use rate (SOUR) of the former are 3.10,
      1.23 times of the latter respectively.

PMID- 16447432
TI  - [Controlling of biological stability in drinking water by purification
      processes].
AB  - In a pilot scale system, the formation and removal of BDOC and AOC were compared
      in the pre-treatment unit, traditional treatment unit and advanced treatment
      unit. The experimental results indicate that the COD(Mn) removal in a traditional
      process plus active carbon filter system is 30% and in a traditional process plus
      ozone and active carbon filter system is more than 50%. The AOC contents in the
      effluent of a traditional process plus active carbon filter system is below 50
      microg/L. The optimum process combination in the research is: traditional process
      plus ozonation plus biological active carbon.

PMID- 16447433
TI  - [Comparison of the quality and toxicity of wastewater after chlorine and chlorine
      dioxide disinfections].
AB  - The effects of chlorine and chlorine dioxide disinfections on quality and
      toxicity of wastewater were compared. The experiment results showed that chlorine
      disinfection had no obvious effect on wastewater color, while chlorine dioxide
      disinfection decreased wastewater color observably. The DOC of wastewater did not
      change much after chlorine and chlorine dioxide disinfections. Chlorine
      disinfection significantly increased UV230 of wastewater and chlorine dioxide
      disinfection slightly decreased UV230 of wastewater. When the disinfectants
      dosage was 30 mg/L, UV230 increased about 0.7 cm(-1) after chlorine disinfection
      and decreased about 0.05 cm(-1) after chlorine dioxide disinfection. The acute
      toxicity of wastewater increased with increasing disinfectants dosage for both
      chlorine and chlorine dioxide disinfections and the acute toxicity after chlorine
      disinfection is much stronger than that after chlorine dioxide disinfection. The
      genotoxicity of wastewater increased slightly after chlorine disinfection and
      decreased slightly after chlorine dioxide disinfection.

PMID- 16447434
TI  - [Study on the combination of preozonation and post-ozonation-BAC process for
      drinking water treatment].
AB  - This study was conducted to illustrate the effectiveness of preozonation or O3
      BAC or combination of these two process in controlling DBPs for treating a dam
      source water in South China through SBR and continuous flow (200 L/h) experiments
      and the variables in the treatment train included the point of preozonation with
      respect to coagulation; the point of ozonation with respect to BAC, the ozone
      dosage required for preozonation and the Br- content of raw water. Results
      indicated the reduction in DBP formation potential closely paralleled the
      reduction in UV absorbance, and trihalomethane and haloacetic acid formation
      potential can be removed under a dose of preozone at 0.5 - 1.0 mg/L, at the same
      time, ozone by-products (bromate and formaldehyde) can be controlled in low
      level. The continuous flow experiment results show that combination of
      preozonation and O3-BAC process has obviously positive effects on the removals of
      particles with a size above 2 microm, COD(Mn), and TOC. However, DBPs formation
      can be controlled by the removal of organic matters.

PMID- 16447435
TI  - [Degradation of nitrobenzene in aqueous solution by modified ceramic honeycomb
      catalyzed ozonation].
AB  - Comparative experiments of modified ceramic honeycomb, ceramic honeycomb
      catalyzed ozonation and ozonation alone were conducted with nitrobenzene as the
      model organic pollutant. It was found that the processes of modified ceramic
      honeycomb and ceramic honeycomb-catalyzed ozonation could increase the removal
      efficiency of nitrobenzene by 38.35% and 15.46%, respectively, compared with that
      achieved by ozonation alone. Under the conditions of this experiment, the
      degradation rate of modified ceramic honeycomb-catalyzed ozonation increased by
      30.55% with the increase of amount of catalyst to 5 blocks. The degradation rate
      of three process all increased greatly with the increase of temperature and value
      of pH in the solution. But when raising the pH value of the solution to 10.00,
      the advantage of modified ceramic honeycomb-catalyzed ozonation processes lost.
      The experimental results indicate that in modified ceramic honeycomb-catalyzed
      ozonation, nitrobenzene is primarily oxidized by *OH free radical in aqueous
      solution. The adsorption of nitrobenzene is too limited to have any influence on
      the degradation efficiency of nitrobenzene. With the same total dosage of applied
      ozone, the multiple steps addition of ozone showed a much higher removal
      efficiency than that obtained by one step in three processes. Modified ceramic
      honeycomb had a relative longer lifetime.

PMID- 16447436
TI  - [Effect of acid-base two steps surface modification on the adsorption of Cr(VI)
      onto activated carbon].
AB  - Effect of HNO3-NaOH two steps surface modification on the adsorption of Cr(VI)
      from aqueous solution onto activated carbon was evaluated. Activated carbon was
      oxidized in HNO3 aqueous solution at first (AC1), then treated in the mixture of
      NaOH and NaCl solution (AC2). Batch equilibrium and continuous adsorption
      experiments were conducted to determine the adsorption characteristics. Boehm
      titration method, element analysis were used to characterize the surface
      properties. N2/77 K adsorption isotherm method was used to characterize the pore
      structure. The results reveal that adsorption capacity and adsorption rate
      increase significantly, which in the following order: AC2>AC1>AC0. Surface
      modification caused BET surface area decreased and the total number of surface
      oxygen acid groups increased. First oxidation modification in HNO3 solution
      produced positive acid groups on the surface of activated carbon. Subsequent 2nd
      modification replaced H+ of carbon surface groups by Na+, the acidity of AC2 was
      decreased. The main cause of higher Cr(VI) adsorption capacity and rate for AC2
      was the more oxygen surface acid groups, and suitable solution pH provide by
      surface groups.

PMID- 16447437
TI  - [Research on Pb2 + removal from wastewater by Sphaerotilus natans].
AB  - As biosorbent used Sphaerotilus natans, influencing factors on removal of Pb2+
      were investigated such as ratio of the biomass and lead, pH, temperature and time
      of adsorption. The results show that Sphaerotilus natans has good effect on
      adsorption of Pb2+. The process of adsorption reached equilibrium in 10 minutes.
      Temperature has no significant effect on the adsorption. Removal of Pb2+
      approached to 100% under the condition of pH 5.5, 0.6 g/L and c0 < or =20 mg/L.
      The maximum adsorption amount was 2.1 mmol/g dry biomass . The adsorption was
      fitted with Freundlich isotherm adsorption equation under the concentration of
      Pb2+ 0-60 mg/L. HCI and EDTA can desorb the Pb2+ from the bacteria effectively.

PMID- 16447438
TI  - [Analysis of microcystins by LC-ESI/MS in the algal cells collected from Guanting
      Reservoir].
AB  - Microcystins in the algal cells collected from the water bloom of the Guanting
      Reservoir were further investigated by LC-ESI/MS after they were studied by the
      method of HPLC. The results show that three of five microcystins contained in the
      algal cells of the blooms are frequent Microcystin-RR, Microcystin-LR and
      Microcystin-YR, whose molecular weights are 1038, 995 and 1045 respectively. The
      molecular weights of the other two microcystins are 1052 and 1009, which are
      corresponding to the molecular weights of Microcystin-YY and Mglu-LR
      respectively, however the complete identification of both MCs have to be carried
      out further.

PMID- 16447439
TI  - [Study of sonochemical degradation of microcystins].
AB  - Sonochemical degradation of microcystins (MC) produced by microcystis in water
      and the influence of various ultrasonic parameters were studied. The results show
      that microcystins could be effectively degraded in ultrasonic fields. 150 kHz is
      the best ultrasound frequency for microcystins degradation, and the removal ratio
      of microcystins reached 70% after 20 min ultrasonic irradiation at 150 kHz and 40
      W. Furthermore, ultraviolet irradiation strengthened the ultrasonic degradation
      of microcystins.

PMID- 16447440
TI  - [Performance improvement of sequencing batch reactor (SBR) treating digested
      piggery wastewater by addition of raw wastewater].
AB  - When digested piggery wastewater was directly treated with a sequencing batch
      reactor (SBR) process, the efficiency was low with COD removal about 10% and NH4+
      -N removal about 70%. The effluent COD concentration was higher than 1000 mg/L
      and effluent NH4+ -N concentration was 200 mg/L or so. The working state of the
      reactor was unstable and its performance deteriorated gradually during operation.
      After adding no-digested piggery wastewater (raw wastewater) to digested piggery
      wastewater in the influent, the reactor performance was significantly improved
      with COD removal higher than 80% and NH4+ -N removal up to 99%. The effluent COD
      concentration was in the range of 250 mg/L to 350 mg/L and effluent NH4+ -N
      concentration was lower than 10 m/L. The working stability of the reactor was
      greatly increased. After adding raw wastewater, the ratio of BOD5 to COD in the
      influent was raised from 0.19 to 0.54, and the ratio of BOD5 to TN was raised
      from 0.28 to 2.04, which implied an increase of carbon source for microbial
      growth and denitrification. The elevated denitrification resulting from the
      increase of carbon source not only promoted the removal of total nitrogen, but
      also stabilized the pH value by supplementing alkalinity to treatment system.

PMID- 16447442
TI  - [Degradation of p-nitrophenol by high voltage pulsed discharge and ozone
      processes].
AB  - The vigorous oxidation by ozone and the high energy by pulsed discharge are
      utilized to degrade the big hazardous molecules. And these big hazardous
      molecules become small and less hazardous by this process in order to improve the
      biodegradability. When pH value is 8-9, the concentration of p-nitrophenol
      solution can be degraded by 96.8% and the degradation efficiency of TOC is 38.6%
      by ozone and pulsed discharge treatment for 30 mins. The comparison results show
      that the combination treatment efficiency is higher than the separate, so the
      combination of ozone and pulsed discharge has high synergism. It is approved that
      the phenyl degradation efficiency is high and the degradation efficiency of
      linear molecules is relative low.

PMID- 16447441
TI  - [Extreme thermophilic (70 degrees C), combining two-phase anaerobic/activated
      sludge/bio-activated charcoal for treating food wastewater].
AB  - This study was conducted to investigate the performance of combining two-phase
      anaerobic(TPA)/activated sludge(AS)/bio-activated charcoal(BAC), seeded with
      mesophilic sludge, for treating food wastewater at extreme temperature (70
      degrees C) to allow treated water to be reused for closed heat water circuits.
      The system had a total hydraulic retention time of 42h. Reactor performance was
      characterized by COD, VFA, pH, amino-acid. An overall COD treatment efficiency of
      99.62%, VFA and amino-acide of 100% and pH between 6.6 - 7.5 were observed for
      the system. COD removal of acidification phase, methane phase, activated sludge
      and BAC was 49.7%, 33.7%, 14.5%, and 1.1%, respectively. VFA removal of methane
      phase, activated sludge and BAC was 56%, 21.2% and 21.8%, respectively. Amino
      acid removal of methane phase, activated sludge and BAC was 34.8%, 62% and 3%,
      respectively. COD concentration of effluent in the system was lower than 50 mg/L.
      An additional experiments show that activated sludge and bio-activated charcoal
      at 70 degrees C may allow COD concentration of influent up to 3500 mg/L and COD
      removal was up to 95.8% at high organic loading 4.5 kg/(m3 x d) with aerobic
      condition.

PMID- 16447443
TI  - [Electrical charges and coagulation efficiency of Al13 species in polyaluminum
      chloride (PAC)].
AB  - The polynuclear Keggin species, Al12AlO4(OH)24(H2O)12(7+) (Al13), was separated
      and purified from polyaluminum chloride (PAC) by gel column chromatographic
      method. The purified Al13 was characterized by Al-Ferron timed complexation
      spectrophotometry method and ZATESIZER 3000HSA tester compared with PAC and
      ALCl3. Jar tests were performed to test the coagulation efficiency of the three
      coagulants in treating synthetic or actual water samples. The results showed that
      Al13 could be obtained by the column chromatographic method and the content of it
      could reach about 99%. Compared with PAC and AlCl3, Al13 gives the best results
      for turbidity, humic acid and color removal, and achieves the highest charge
      neutralizing ability. Al13 species is a higher positive-charged and wide pH range
      application, it is much more steady in hydrolyze process and most effective
      polymeric Al species in water and wastewater treatment.

PMID- 16447444
TI  - [Response of POD and CAT during seeds of rice, wheat and rape germination on acid
      rain stress].
AB  - The effects of simulated acid rain (pH 2.5 - 5.0) on the activities of POD and
      CAT were investigated during germination of rice (O. sativa), wheat (T. aestivum)
      and rape (B. chinensis var. oleifera) seeds. Compared with the control (CK), the
      amplitude of the change in the activity of CAT and POD is that rice (28.8%,
      31.7%) < wheat (34.7%, 48.3%) < rape (79.3%, 50.0%), respectively. The pH
      significantly different (p < 0.05) from CK follows the order: rice (3.5) > wheat
      (4.0) > rape (5.0). All of these revealed that the ability of resisting acid rain
      stress is that rice is stronger than wheat and rape is the worst. Under the same
      condition, the amplitude of the change in the activity of CAT is more sensitivity
      toward acid rain stress than that of POD. The difference in free radicals removed
      by these 3 species is one of the reasons why the germinating indexes behaved
      differently.

PMID- 16447445
TI  - [Influence of NTA on accumulation and subcellular distribution of copper and zinc
      in corn (Zea mays)].
AB  - The differential centrifugation method was used to study the subcellular
      distribution of Cu and Zn in the roots, stems and leaves of corn (zea mays)
      growing on multi-metal contaminated soil with the addition of chelator
      Nitrilotriacetic Acid (NTA). The results show that the subcellular distributions
      of Cu and Zn have significant relationship with the ability of metal uptake and
      accumulation in corn. NTA could evidently promote the uptake and accumulation of
      Cu and Zn in corn and affect on their distribution in cell wall and vacuole. Most
      of Cu was bound to the cell wall fraction and secondly cytoplasm fraction and
      only a small quantity of Cu bound to organelle fractions. For Zn, however, most
      of Zn was bound to cytoplasm fraction and there was more Zn bound to organelles
      than Cu. Under the inducement of NTA, there were increasing Cu and Zn bound to
      cytoplasm fraction, which mostly came from cell wall fraction and partly came
      from organelle fractions.

PMID- 16447446
TI  - [Aging of spiked pyrene in two paddy soils and their particle-size fractions
      after soil incubation and changes in extractability and bio-availability to
      earthworm].
AB  - Effect of aging on bioavailability and extractability of persistent organic
      pollutants has recently been paid much attention in environmental studies. This
      study deals with aging of spiked pyrene, a four-ring polycyclic hydrocarbon, in
      two paddy soils and their particle-size fractions under laboratory incubation and
      change in its extractability and bioavailability. The bioavailability of aged
      pyrene was tested by an assay of exposure to earthworms (Eisenia foetida). The
      extractability of spiked pyrene was decreased by 15% to 23%, and the
      bioavailability to earthworm was decreased by 37% to 67% after incubation for 90
      d compared to under no incubation. Meanwhile, there was no significant difference
      in the pyrene extractability between incubation with different size fractions of
      a single soil. Soil incubation resulted in lower extractability and, thus, lower
      environmental risk of the organic pollutants after incorporation in paddy soils
      and their aggregates. The different size fractions of paddy soils may exert
      different bioavailability when exposure to soil fauna. Thus, content and chemical
      extractability may not be appropriate index for assessing the potential
      environmental risk and bioavailability to soil fauna for persistent organic
      pollutants in paddy soils.

PMID- 16447447
TI  - [Hysteretic characteristics of atrazine desorption from fluvo-aquic soil].
AB  - Kinetic batch experiments are carried out in order to investigate the effects of
      a wide range of atrazine initial concentrations and consecutive desorption time
      on the desorption characteristics of atrazine from fluvo-aquic soil. The results
      reveal that, atrazine concentrations in soil solution gradually decreased with
      desorption time increasing, whose relationship can be expressed with empirically
      exponential functions. After consecutive five steps (or 5 days), when atrazine
      initial concentrations increased from 50 microg x L(-1) to 2000 microg x L(-1),
      the average desorption percentages were 23.1%, 30.4%, 33.0%, 36.4% and 38.5%,
      respectively. The relationships between the amount of atrazine adsorbed by soil
      colloids and corresponding atrazine concentrations in soil solutions may be
      described through the traditional and time-dependent desorption isotherms. The
      obvious discrepancies in two families of both traditional and time-dependent
      desorption isotherms from adsorption isotherm, which retention time last for 168
      hours before commencement of desorption, were indicative of hysteresis. Two sets
      of Freundlich parameters derived from both desorption isotherms can quantify the
      hysteresis between desorption and adsorption isotherms. However, hysteresis
      coefficient, omega, was applicable only for the traditional desorption isotherms,
      H and lamda applicable for both.

PMID- 16447448
TI  - [Bidens maximowicziana's adsorption ability and remediation potential to lead in
      soils].
AB  - Bidens maximowicziana's adsorption ability and remediation potential to lead were
      studied. The results show: (1) The Bidens maximowicziana has a strong adsorption
      to lead, the concentration of lead in plants increased linearly with the increase
      of lead concentration in soil. Then maximum concentration was 1509.3 mg x kg(-1)
      in roots and 2164.7 mg x kg(-1) in shoots when lead concentration in soil was
      2000 mg x L(-1); (2) The lead concentration distribution order in the Bidens
      maximorwicziana is: leaf>stem>root>seed, which indicate that Bidens
      maximowicziana has a strong ability to transfer lead; (3) Uptaking ability
      differes in different vegetal periods. Maximum lead uptaking rate occured in the
      period of blooming for 40-60 days, in which daily uptake capacity was 15.81 mg x
      (kg x d)(-1) in roots and 19.83 mg x (kg x d)(-1) in shoots respectively. It can
      be concluded that Bidens maximowicziana appeares to be a moderate Pb accumulator
      making it suitable for phytoremediation of Pb contaminated soil.

PMID- 16447449
TI  - [Study on benzene degraded by soil microorganism].
AB  - The experiments were made in laboratory to analyze the characteristics and
      principle of benzene's biodegradation using the microorganism (G-,
      Flavobacterium) taken from Daqing oil fields. Results show that the maximal
      concentration of benzene, which microorganisms could endure is between 8.8 mg x
      L(-1) and 17.6 mg x L(-1); microorganisms were inhibited as benzene's
      concentration was beyond 17.6 mg x L(-1). Trends of benzene's concentration in
      and out of microorganism's cell are almost same; the biodegradation could be
      achieved efficiently as the pH range of 6.5 - 7.0 and benzene initial
      concentration range of 7.04 - 13.2 mg x L(-1). Change of - lgP (P is the
      distributive ratio of benzene in membrane and water) could be illustrated the
      trends of toxicity and degradation of benzene in and out of microorganism's cell;
      the biodegradation rate varied simultaneously with the change of P as initial
      concentration of benzene was beyond 8.8 mg x L(-1).

PMID- 16447450
TI  - [Influence of soil lead upon children blood lead in Shenyang City].
AB  - The dynamic correlation coefficients between soil lead and blood lead, the
      children blood lead arose from soil lead and the length of time over which the
      blood lead concentration can fall to be at or below the threshold value (10
      microg x dL(-1)) are analyzed. If the aggregated soil lead and blood lead are
      stratified by the seven geographic regions studied, an elevated R of 0.9200 could
      be calculated, and the lead exposure assessment may require knowledge of
      geographic dimension of the exposure topology components. The children blood lead
      levels calculated based on the soil lead in the unit of geographic region show
      that the blood lead levels of about 90% of children exceed the threshold value in
      the west industrial area, while they are all below the threshold value in the
      east area. The children, whose blood lead level exceed the threshold value, are
      in the range of 3.48% - 31.81% in the other areas. The length of time over which
      the blood lead concentration can fall to be at or below the threshold value is
      highest, and average 26.68months, in the west area, and the order is the west >
      the north > the northeast > the southwest > the northwest > central area > the
      east, it is zero in the east area, and the maximum recovery time follow the same
      order. The blood lead levels and the recovery time are controlled by the
      environmental lead contamination, and the lead hazard intervention would
      contribute to the fall of blood lead levels.

PMID- 16447451
TI  - [Degradation regulation of fenthion and chlorfenvinfos combined pollutants in red
      soil].
AB  - The degrading regulations of combined pollutants of chlorfenvinfos and fenthion
      in red soil were studied, in which soil incubation, gas chromatography with
      nitrogen-phosphorus detection for analysis are utilized. The main conclusions
      drawn are as follows: under combined pollution condition, the degrading amount of
      fenthion was significantly higher than that of fenthion alone in soil; under
      saturated soil humidity, the degrading amount of fenthion was less changed, while
      that of chlorfenvinfos was increased by 33.3% - 1250%. Soil drought made
      degradation amount of fenthion decreased a little, while made chlorfenvinfos
      increased significantly prior to the 21st day after addition of pesticide;
      nitrogen fertilizer application stimulated both fenthion and chlorfenvinfos
      degraded; the chemical degrading amount of fenthion in soil with organic matter
      eliminated was decreased by 22.4% - 30.8%, while that of chlorfenvinfos was
      increased 42.1% - 2370% at the earlier stage, and was decreased 11% - 17.3% at
      the later stage. Therefore, there are differences of degrading regulation between
      single pesticide pollutant and combined pesticide pollutants in soil, and the
      degradation of organophosphorus pesticides in combined pollutants are influenced
      with each other.

PMID- 16447452
TI  - [Enzymatic degradation of organophosphorus insecticide chlorpyrifos by fungus WZ
      I].
AB  - Degradation characteristics of chlorpyrifos insecticides was determined by the
      crude enzyme extracted from the isolated strain WZ-I ( Fusarium LK. ex Fx). The
      best separating condition and the degrading characteristic of chlorpyrifos were
      studied. Rate of degradation for chlorpyrifos by its intracellular enzyme,
      extracellular enzyme and cell fragment was 60.8%, 11.3% and 48%, respectively.
      The degrading enzyme was extracted after this fungus was incubated for 8
      generations in the condition of noninducement, and its enzymic activity lost
      less, the results show that this enzyme is an intracellular and connatural
      enzyme. The solubility protein of the crude enzyme was determined with Albumin
      (bovine serum) as standard protein and the solubility protein of the crude enzyme
      was 3.36 mg x mL(-1). The pH optimum for crude enzyme was 6.8 for enzymatic
      degradation of chlorpyrifos, and it had comparatively high activity in the range
      of pH 6.0 - 9.0. The optimum temperature for enzymatic activity was at 40 degrees
      C, it still had comparatively high activity in the range of temperature 20-50
      degrees C, the activity of enzyme rapidly reduced at 55 degrees C, its activity
      was 41% of the maximal activity. The crude enzyme showed Km value for
      chlorpyrifos of 1.049 26 mmol x L(-1), and the maximal enzymatic degradation rate
      was 0.253 5 micromol x (mg x min)(-1). Additional experimental evidence suggests
      that the enzyme had the stability of endure for temperature and pH, the crude
      enzyme of fungus WZ-I could effectively degrade chlorpyrifos.

PMID- 16447453
TI  - [Determination of 2,4-D using disposable amperometric immunosensor].
AB  - 2,4-Dichlorophenoxyacetic Acid (2,4-D) is the herbicide widely applied in the
      world. An amperometric immunosensor to detect 2,4-D was described. Firstly, 2,4-D
      protein conjugate was prepared using 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide hydrochloride (EDC). The rabbit antiserum was prepared with
      substitution degree of 16. Secondly, the immunosensor was fabricated using screen
      printing technique. The 2,4-D/PLL conjugate was immobilized on the surface of
      screen printed carbon electrode via crosslinking method. The free and immobilized
      2,4-D competed the binding sites of anti-2,4-D antiserum. After HRP-labeled goat
      anti-rabbit IgG binding with anti-2,4 antiserum, the substrate was added and
      current response was recorded. The dependency of concentration of antiserum and
      HRP-labeled anti-IgG on current response was also studied. The result shows that
      limit of detection for 2,4-D is 1. 69 ng/mL with linear range 1.69 - 30000 ng/mL,
      which reveal the potential ability to evaluate the safety of drinking

PMID- 16447454
TI  - [Effect of pH on suppressing the growth of other bacteria and fungi in culturing
      Phanerochaete chrysosporium in liquid medium].
AB  - Effect of different pH value on suppressing the growth of other bacteria and
      fungi in culturing Phanerochaete chrysosporium in liquid medium under non-sterile
      were investigated in agitated Erlenmeyer flasks. Results showed that nitrogen
      limited liquid medium with pH3.6 and pH4.4 were contaminated only by yeast fungi
      when the Phanerochaete chrysosporium was incubated with spore inoculation under
      non-sterile condition for one day; however, nitrogen-limited liquid medium with
      pH5.6 was contaminated not only by yeast, but also by bacteria. These
      contaminated yeast and bacteria reduced the dye decolorizing ability of
      Phanerochaete chrysosporium . If after the Phanerochaete chrysosporium was
      incubated under sterile condition for 5 days, it can decolorize over 70% of the
      reactive brilliant red K-2BP within 45 hours under non-sterile condition, and
      this removal rate was close to or even higher than that under sterile condition.
      Phanerochaete chrysosporium cultured in the liquid medium with pH4.4 have the
      best decolorizing effect under non-sterile condition, and can decolorize up to
      80% of the reactive brilliant red K-2BP in 24 hours. In additions, it was
      observed that by using the Phanerochaete chrysosporium incubated in above
      nitrogen-limited liquid medium with different pH under sterile condition for 5
      days, the system were also contaminated by the other bacteria and yeast during
      decolorizing reactive brilliant red K-2BP under non-sterile condition, but the
      amount of these bacteria and yeast in liquid medium were too little to influence
      the Phanerochaete chrysosporium decolorizing reactive brilliant red K-2BP. So
      that, when Phanerochaete chrysosporium was used to decolorize reactive dyes under
      non-sterile condition, the incubation of Phanerochaete chrysosporium must be
      operated under sterile condition in order to achieve the higher decolorization.

PMID- 16447455
TI  - [Bioleaching of fly ash from municipal solid waste incinerator using sewage
      sludge and pig manure as culture media].
AB  - A mixed culture of Acidihiobacillus ferrooaidans and Acidihiobacillus thiooxidans
      was used to leach heavy metals from municipal solid waste incineration fly ash
      (MSWI fly ash). This study explored the possibility of using sewage sludge or pig
      manure as nutrients for supporting the growth of the leaching bacteria and
      allowing metal solubilization like a synthetic mineral medium. In contrast to pig
      manure, there is a high ability for acidification of the fly ash and
      solubilization of toxic metals using sewage sludge at the same content. After 15
      d of bioleaching, the following removal efficiencies were obtained for the
      treatment with the addition of 1% sewage sludge: Cd 88.1%; Zn 78.7%; Cu 69.6%,
      whereas their removal efficiencies for the treatment with the addition of 1% pig
      manure were 82.4%, 73.5% and 60.0%, respectively. Results demonstrate that the
      inhibition by sewage sludge DOM is much more significant than by pig manure DOM
      at the same concentration level. The dissolved organic carbon in excess of 400
      and 150 mg/L was inhibitory to the bacterial growth using sludge DOM and manure
      DOM, respectively. Compared with sewage sludge, pig manure contained a higher
      fraction of DOM with molecular size <1000, which led to its higher toxicity.

PMID- 16447456
TI  - [Migration characteristics of heavy metals during sintering of fly ash from
      municipal solid waste incinerator].
AB  - The sintering process is used to stabilize the heavy metal in fly ash from
      municipal solid waste incinerator (MSWI). Migration characteristics of 6 targeted
      heavy metals (Cd, Pb, Cu, Ni, Cr and Zn) in the sintering process of MSWI fly ash
      were investigated by experiments. Effect of several factors including sintering
      temperature, residence time, molding pressure and particle diameter on the
      migration of heavy metals were discussed in details. The results show that
      cadmium and lead are volatile metals, while nickel, copper, chromium and zinc
      belong to involatilizable metals. The effects of sintering temperature, residence
      time, molding pressure and particle diameter on the stabilizing efficiency differ
      from each other. The study shows that most of heavy metals are stabilized during
      the sintering process. The stabilizing efficiency of heavy metals was different
      for different elements.

PMID- 16447457
TI  - [Prediction of landfill leachate production in cold area conversion].
AB  - Leachate production is evidently discontinuous in the chilly northeast areas
      because of the distinct 4-seasons conversion and long frozen time. In order to
      investigate into the leachate production variability and the impact of leachate
      recirculation on sanitary landfill, two simulated landfill reactors were
      constructed outdoors, which were filled with the same municipal solid waste. One
      reactor was provided with leachate recirculation and the other without as a
      control. On the basis of the obtained leachate production data and evaluation of
      the available leachate predictive models, the empirical model was recommended and
      the parameters within the formula were determined through linear regression
      analysis, which was proved to be reliable and practical. The results provided a
      scientific basis for the prediction of leachate production, design of leachate
      collection and treatment system. Besides, this study indicated that leachate
      recirculation was feasible for leachate treatment in the cold areas.

PMID- 16447458
TI  - [Application of linear programming in the allocation of environmental capacity
      resources].
AB  - This paper analyzes the application of optimization approaches, particularly the
      application types of the linear programming (LP) model in environmental planning
      and management; put forwards the objective function models and their constraint
      conditions. Based on the formulation of linear programming model related to
      environmental planning the paper develops the allocation model of environmental
      purification capacity (EPC), and identifies the constraints to EPC allocation and
      their parameters or co-efficiencies. It is proved that LP approach is a practical
      and scientific tool for allocating EPC in specific region.

PMID- 16447460
TI  - Hand washing.

PMID- 16447459
TI  - Electronic prescriptions: the wave of the future?

PMID- 16447461
TI  - Terminology, technology, and troubleshooting: Q & A.

PMID- 16447463
TI  - Taking the hit out of sports injuries.

PMID- 16447462
TI  - Extend the life of your handpiece: maintenance & sterilization tips.

PMID- 16447464
TI  - Setting up and maintaining a dental office safety program.

PMID- 16447465
TI  - Putting it all together. An effective dental office safety program.

PMID- 16447466
TI  - Small bowel necrosis related to enteral nutrition after duodenal surgery.
AB  - Nutritional support is the key to the successful recovery of any patient. Small
      bowel necrosis is described in patients being fed with enteral nutrition after
      surgery. Five patients with small bowel necrosis after surgery will be discussed
      and an etiology proposed. A retrospective review of patient data was performed.
      Data was collected on the type of surgical procedures performed, the enteral
      nutrition given to the patient, basic laboratory data, the length of stay, and
      discharge status. A total of five patients' charts were reviewed. Three patients
      had pancreaticoduodenectomy for a pancreatic mass and two required pyloric
      exclusion secondary to gunshot wounds. All five patients were fed with a fiber
      based enteral nutrition. All patients subsequently had small bowel necrosis
      requiring reoperation. Four of the five patients had inspissated tube feeding
      within the necrotic small bowel. Two patients died and three survived with
      prolonged hospital courses. We propose that the combination of duodenal surgery
      and fiber-based enteral nutrition contribute to the development of small bowel
      necrosis postoperatively.

PMID- 16447467
TI  - Cirrhosis and trauma: a deadly duo.
AB  - It has been previously reported that trauma patients with cirrhosis undergoing
      emergency abdominal operations exhibit a fourfold increase in mortality
      independent of their Child's classification. We undertook this review to assess
      the impact of cirrhosis on trauma patients. We reviewed the records of patients
      from 1993 to 2003 with documented hepatic cirrhosis and compared them to a 2:1
      control population without hepatic cirrhosis and matched for age, sex, Injury
      Severity Score (ISS), and Glasgow Coma Score (GCS). Demographic, severity of
      injury, and outcome data were recorded. Student's t test and X2 were used for
      statistical analysis and a P < 0.05 was significant. Sixty-one patients had
      documented cirrhosis and were compared to 156 matched controls. Comparing the two
      groups demonstrates there was no difference in age, ISS, or GCS. Intensive care
      stay, hospital length of stay, blood requirements in the first 24 hours
      postinjury, and mortality (33% vs 1%) was significantly greater in the trauma
      patients with cirrhosis. Fifty-five per cent of deaths in the cirrhosis group was
      due to sepsis, and, as the Child's class increases, so does the mortality
      (Child's A, 15%; B, 37%; and C, 63%). In 64 per cent of cirrhotics without an
      emergent abdominal operation, mortality was 21 per cent. In the 36 per cent of
      cirrhotics who had emergent abdominal operation, mortality was 55 per cent.
      Hepatic cirrhosis in trauma patients, regardless of severity of injury or the
      need for an abdominal intervention, is a poor prognostic indicator. The necessity
      of an abdominal operative intervention further amplifies this effect. Trauma and
      cirrhosis is, in fact, a deadly duo.

PMID- 16447468
TI  - Endovascular aortic aneurysm repair with the Zenith AAA Endovascular Graft: does
      gender affect procedural success, postoperative morbidity, or early survival?
AB  - The purpose of this study was to analyze the effect of gender on deployment,
      early morbidity, and survival after endovascular aortic aneurysm repair (EVAR)
      using the Zenith Endovascular Graft. Data were obtained from the U.S. Multicenter
      Zenith Endograft trial and complemented with results from the Zenith female
      registry, including 40 women (10.9%) and 326 men (89.1%). Data analysis included
      preoperative medical risk factors, aneurysm morphology, deployment, and
      postoperative morbidity data, and 30-day and 1-year results. Preoperatively,
      women more often had experienced thromboembolic events (13% vs 4.3%; P = 0.04),
      but less angina pectoris (24% vs 49%; P = 0.002) or myocardial infarction (18% vs
      38%; P = 0.01) compared with men. Women had more angulated aneurysm necks and
      narrower iliac arteries compared with men. Procedural success, cardiovascular,
      pulmonary, renal, bowel-related, neurologic, or other adverse events were
      comparable, as were 30-day and 1-year survival. Females experienced more wound
      dehiscences (5.0% vs 0.0%; P = 0.01) and open surgical conversions in the first
      year (5%) compared with men (0.31%) (P = 0.03). With more challenging aneurysm
      morphologies, women were found to be at a higher risk for conversion in the first
      year after EVAR using the Zenith endograft. This however does not translate into
      inferior survival or higher overall morbidity compared with men.

PMID- 16447469
TI  - Civilian craniocerebral gunshot wounds: an update in predicting outcomes.
AB  - Given the high mortality in patients sustaining intracranial injury secondary to
      gunshot wounds (GSWs), predictors to identify patients at increased risk of death
      are needed to assist clinicians early in determining optimal treatment. There
      have been few recent studies involving penetrating craniocerebral injuries, and
      most studies have been restricted to small numbers of patients, which do not
      allow for adequate prediction of mortality. A retrospective chart review of 298
      patients who sustained GSWs to the head between 1992 and 2003 was conducted at a
      level 1 trauma center. Demographics, bullet trajectory, admitting Glasgow Coma
      Scale (GCS), head Abbreviated Injury Score (AIS), as well as admission blood
      pressure and respiratory rate were evaluated. Univariate testing followed by
      multivariate logistic regression was performed to identify independent predictors
      of death. In-hospital mortality for patients with intracranial injury secondary
      to GSW was 51 per cent. A GCS <5 on admission and a high Injury Severity Score
      (ISS >25) was associated with mortality as compared with survivors (P < 0.05). Of
      those patients presenting with a GCS of 3, there were seven survivors to
      discharge. Logistic regression identified the following variables as predictors
      of death: respiratory arrest on admission, hypotension on admission,
      transhemispheric and transventricular GSW. Identification of those patients at
      the highest risk of death secondary to a craniocerebral GSW allows clinicians to
      better predict outcome and prognosis. This is not only important in determining
      treatment algorithms for physicians but also for appropriate counseling of family
      members to educate them with regard to patients' outcomes.

PMID- 16447470
TI  - Lung cancer screening with low-dose spiral computed tomography.
AB  - Computed tomography (CT) has been compared to plain radiographs and bronchial
      washings as a screening tool for lung cancer. In comparison with other screening
      modalities, CT allows detection of lung lesions at an earlier cancer stage.
      Technologic improvements have decreased imaging costs, thus making chest CT a
      more feasible option as a screening tool in the community hospital. In this
      study, smokers over the age of 45 years with a greater than 20 pack-year smoking
      history were referred for screening chest CT. Noncalcified nodules larger than 10
      mm underwent CT-guided biopsy, and smaller nodules underwent follow-up CT in 3
      months. Currently, patients have been followed for 4 years. The prevalence,
      stage, and histology of lung cancer were compared to study results from academic
      centers. Eighty-seven patients underwent screening chest CT. The study population
      was 51 per cent male with a mean age of 64 +/- 9 years. Four (3 female and 1
      male) patients were biopsied and found to have lung cancer giving a prevalence of
      5 per cent. Stage IA disease was found in three patients and stage IIIA disease
      was found in one patient. Adenocarcinoma was present in two patients, adeno
      squamous carcinoma in one patient, and squamous cell carcinoma in one patient.
      The stage and histology of lung carcinomas in this study were comparable to
      studies performed at larger institutions. However, the disease prevalence was
      almost double the highest prevalence found in other studies. This discrepancy
      could be related to study size, as the patient populations were similar. Clearly,
      screening chest CT in the community setting is equally efficacious in the
      diagnosis of lung cancer at earlier stages. Following these patients beyond the 5
      year mark will give some insight on the effect of screening chest CT on the
      mortality of lung cancer.

PMID- 16447471
TI  - Evaluation of a tensiometer to provide objective feedback in knot-tying
      performance.
AB  - Training and assessment methods for knot tying by medical students or residents
      have traditionally been subjective. Objective methods for evaluating creation of
      a tied knot should include assessing the strength and quality of the knotted
      suture. The purpose of this study was to evaluate the use of a tensiometer as a
      feedback device for improving knot-tying performance. Twelve medical students
      with no knot-tying experience were selected to perform three-throw instrument
      ties with 00 silk suture. Students were randomly assigned to perform between 10
      and 20 baseline knots and then received one of four feedback training conditions
      followed by 10 completion knots. Subjects were timed, and all knots were pulled
      in the tensiometer to assess for strength and slippage. Differences between
      baseline and completed knots for each subject were analyzed with an unpaired t
      test. Subjects receiving both subjective and tensiometer feedback demonstrated
      the greatest improvements in knot quality score (KQS) and slip percentage
      (Subject 1: 0.15 +/- 0.9 vs 0.21 +/- 0.05, P < 0.04, 75% vs 60%, P = NS; Subject
      2: 0.22 +/- 0.10 vs 0.29 +/- 0.05, P < 0.02, 33% vs 0%, P < 0.05; Subject 3: 0.10
      +/- 0.07 vs 0.25 +/- 0.07, P < 0.0001, 60% vs 10%, P < 0.01). Objective
      assessment of knot-tying performance is possible using the tensiometer device.
      Introduction of the tensiometer during the learning phase produced improved KQS
      and slip percentage in most students regardless of the number of baseline knots
      tied. Greatest improvements in performance were seen when the tensiometer was
      used in combination with subjective instruction.

PMID- 16447472
TI  - The rate of adenocarcinoma in endoscopically removed colorectal polyps.
AB  - The purpose of this study was to determine the rate of cancer in a modern series
      of colorectal polyps. All pathology reports from colon and rectal polyps from
      1999 to 2002 were reviewed. Reports of bowel resections, cancer-free polyps, and
      polyp-free mucosal biopsies were excluded. Polyps were grouped by size, and the
      rate of adenocarcinoma was determined. x2 was used for analysis. A total of 4,443
      polyps were found, of which 3,225 were adenomatous [2,883 (89.4%) tubular
      adenomas, 399 (9.3%) tubulo-villous adenomas, 32 (1.0%) villous adenomas, and 11
      (0.3%) carcinomas]. The rate of adenocarcinoma by size was 0.07 per cent for
      polyps <1 cm, 2.41 per cent for polyps 1-2 cm, and 19.35 per cent for polyps >2
      cm, representing significantly fewer cancers for each category of polyp size than
      the accepted standard. The rate of carcinoma in colon polyps is much lower than
      previously thought and currently stated in many texts. These data do not alter
      the recommendations for polyp removal, however, failure to retrieve a specimen in
      a polyp <1 cm in size is unlikely to have an adverse outcome because the chances
      of malignancy are very low.

PMID- 16447473
TI  - Nonfunctioning pancreatic endocrine tumor presenting with hemorrhage from
      isolated gastric varices.
AB  - Hemorrhage from gastric varices due to left-sided portal hypertension is an
      unusual presentation for pancreatic endocrine tumor. A case of pancreatic
      endocrine tumor presenting with gastric variceal hemorrhage secondary to left
      sided portal hypertension associated with splenic vein occlusion is presented. A
      53-year-old man with hemorrhage from isolated gastric varices was referred to our
      hospital. Laboratory studies revealed normal liver function. Surveys to identify
      the cause of gastric varices by an abdominal CT, MRCP, and abdominal angiography
      revealed splenic vein occlusion secondarily attributed to the pancreatic tail
      tumor and splenomegaly. The pancreatic tumor was suspected to be a resectable
      endocrine tumor. A distal pancreatectomy, splenectomy, partial resection of the
      gastric fundus, and limited lymph node dissection were performed. By the
      histological examination, the diagnosis of nonfunctioning pancreatic endocrine
      tumor with malignant potential was determined. Three years after the surgery, the
      patient is doing well and reveals no sign of recurrence. In this case, the
      unusual presentation for pancreatic endocrine tumors such as a gastric variceal
      hemorrhage had an advantage that led to early presentation prior to the
      development of metastases with possible curative surgery.

PMID- 16447474
TI  - Newly diagnosed breast cancer patients choose bilateral mastectomy over breast
      conserving surgery when testing positive for a BRCA1/2 mutation.
AB  - In women diagnosed with breast cancer and testing positive for a BRCA1/2
      mutation, decisions as to whether to undergo prophylactic risk-reduction surgery
      may differ from those women who test positive in a presymptomatic phase. Eighty
      four women were identified who had undergone genetic testing at the time of
      breast cancer diagnosis. The study group consisted of 46 of these women who had
      initially undergone breast-conserving surgery. Eight patients (17.4%) tested
      positive for a mutation. Seven of the eight underwent bilateral prophylactic
      mastectomy prior to receiving radiation therapy. The only patient not undergoing
      bilateral mastectomy was awaiting liver transplant. Women who are candidates for
      breast-conserving surgery and who test positive for a breast cancer gene mutation
      choose mastectomy over surveillance.

PMID- 16447475
TI  - Subdiaphragmatic bronchogenic cysts: a comprehensive review of the literature.
AB  - Bronchogenic cysts are foregut-derived developmental anomalies most commonly
      encountered in the mediastinum and rarely in the abdomen or retroperitoneally. A
      comprehensive review of the English-language literature of subdiaphragmatic
      bronchogenic cysts (sBCs) revealed only 48 reported cases of sBC. Although most
      cases are incidentally discovered, preoperative differential diagnosis often
      includes tumors with malignant potential and necessitates surgical resection to
      obtain a definitive diagnosis. Herein, we describe a case of a 46-year-old female
      presenting with intermittent left flank pain, upon which computed tomography
      demonstrated a retroperitoneal mass. Upon resection, histopathology revealed the
      mass to be a thin-walled cystic mass lined by ciliated columnar cells and
      cartilage, consistent with a subdiaphragmatic bronchogenic cyst. A comprehensive
      literature review of sBC was also performed.

PMID- 16447476
TI  - Laparoscopic-assisted peritoneal dialysis catheter placement, an improvement on
      the single trocar technique.
AB  - In 2002, Ochsner laparoscopic surgeons and nephrologists began placing peritoneal
      dialysis (PD) catheters via a laparoscopic-assisted method. We compared
      laparoscopically placed PD catheters (LAPD) with catheters most recently placed
      without laparoscopic aid (STPD). The method for this study is a retrospective
      chart review. Demographics of both groups were similar. Nine of 20 (45%) in the
      STPD group and 16 of 23 (70%) in the LAPD group had had previous abdominal
      surgery. Three of 20 (15%) of STPD had complications, including one small bowel
      injury. Four of 23 (17.4%) of the LAPD had complications. One of 20 (5%) in the
      STPD group and 3 of 23 (13%) in the LAPD group had dialysate leaks. In the STPD
      group, 8 of 20 (40%) had catheter problems that led to removal in 7 (35%). In the
      LAPD group, 6 of 23 (26%) had catheter malfunction: 3 were salvaged with a
      laparoscopic procedure; 3 (13%) were removed for malfunction. 1) LAPD allows
      proper PD placement after complex abdominal surgery; 2) Although dialysate leak
      complications are increased, bowel perforation risk is less; 3) Because of proper
      placement, PD catheter malfunction rate is less with LAPD; 4) Although no results
      obtained statistical significance, we found LAPD superior to STPD and have
      converted to this technique.

PMID- 16447477
TI  - Acellular dermal matrix (AlloDerm): new material in the repair of stoma site
      hernias.
AB  - Parastomal hernias are a common complication after ileostomy or colostomy
      formation and can lead to complications, such as intestinal obstruction and
      strangulation. When a parastomal hernia presents, repair of the defect can pose a
      challenge to the surgeon to choose a repair that both reduces complications and
      recurrence rates. We present three cases of parastomal hernia repair using
      acellular dermal matrix (AlloDerm) as reinforcement to the primary hernia repair.
      We prospectively followed three patients who presented with parastomal hernia
      after ostomy formation in 2001-2002. The patients underwent repair of the
      parastomal hernia using primary fascial repair with reinforcement using AlloDerm
      as an on-lay patch. Two patients were followed for 6 months and 1 year,
      respectively, and remained hernia-free. One patient presented 8 months later with
      symptoms of intestinal obstruction that were relieved by nasogastric tube
      decompression and bowel rest. The patient subsequently returned 3 months later
      with intestinal obstruction and recurrent parastomal hernia that necessitated an
      operation for relocation of the stoma and repeat hernia repair. Repair of
      parastomal hernias using AlloDerm acellular dermal matrix as a substitute for a
      synthetic graft showed resilience to infection and, more importantly, tolerated
      exposure in an open wound without having to be removed. Larger studies with
      longer follow-up are needed to see if this material reduces the incidence of
      hernia recurrence.

PMID- 16447478
TI  - Calcifying fibrous pseudotumor of the neck: diagnostic challenges of a rare
      benign lesion.
AB  - Neck masses, frequently encountered by physicians, comprise a vast range of
      diagnoses, with malignancy being the greatest concern. Calcifying fibrous
      pseudotumor (CFP) is a rare lesion with unknown pathogenesis, characterized
      pathologically by a predominance of abundant hyalinized collagenous tissue with
      focal lymphoplasmacytic infiltrate and psammomatous or dystrophic calcifications.
      We present the case of a 29-year-old woman who presented with a 4-cm left neck
      mass, accompanied by constitutional symptoms of vague weakness and lethargy.
      After the lesion failed to respond to a course of antibiotic therapy, fine-needle
      aspiration was performed, the pathology of which was indeterminate. The concern
      was that the lesion was a lymphoproliferative disorder-further workup was
      performed. CT of the chest, abdomen, and pelvis revealed no evidence of
      adenopathy or neoplasms. Subsequently, an incisional biopsy was performed,
      suggesting a diagnosis of CFP. Magnetic resonance imaging with contrast,
      performed to delineate the anatomy, revealed the lesion in the left neck, deep to
      the left clavicle, that extended superiorly into the supraclavicular fossa.
      Complete surgical removal of the lesion was successfully performed, with
      immunophenotyping confirming the initial diagnosis of CFP. We present a case
      report of cervical CFP, discuss the approach to neck masses, and review the
      recent literature on this rare, benign entity.

PMID- 16447479
TI  - Laparoscopic removal of an intrauterine device perforating the sigmoid colon: a
      case report and review of the literature.
AB  - We report a case of a translocated intrauterine device (IUD) embedded within the
      colon wall. Endoscopic tattooing and laparoscopy was used to identify the colonic
      site and facilitate extraction by colonic resection. A review of the literature
      and discussion of laparoscopic management of this complication is presented.

PMID- 16447480
TI  - Colobronchial fistula as a rare complication of coloesophageal interposition: a
      unique treatment with a review of the medical literature.
AB  - Colobronchial fistula after coloesophageal interposition is a rare complication
      that has only been reported once in the English surgical literature. We report
      the case of a 53-year-old man who presented with chronic respiratory complaints.
      He had previously undergone esophagectomy for adenocarcinoma of the
      gastroesophageal junction. The fistula was controlled by placement of a Polyflex
      esophageal stent.

PMID- 16447481
TI  - Bile duct injuries during laparoscopic cholecystectomy: management and outcome.
AB  - The aim of this study is to analyze our experience with the management of bile
      duct injuries (BDIs) following laparoscopic cholecystectomy (LC). From 1996 to
      2004, 21 patients with BDI after LC were treated in our department. The BDIs were
      graded according to the classification of Strasberg. Ten patients had minor BDI.
      Minor injuries were classified as A in six and D in four patients. In three
      patients, endoscopic retrograde cholangiopancreatography sphincterotomy and stent
      placement was adequate treatment. Six patients required laparotomy and bile duct
      ligation or suturing, and one patient underwent laparoscopy with additional
      ligation of a duct of Luschka. Eleven patients had major BDIs. These injuries
      were classified as E1 in two, E2 in three, E3 in four, and E4 in two patients.
      Among the patients with a major BDI, Roux-en-Y hepaticojejunostomy was performed.
      After a median follow-up of 69.45 months, no evidence of biliary disease has been
      detected among our patients. BDIs should be managed in a specialist unit where
      surgeons skilled to perform such repairs should undertake definitive treatment.
      Roux-en-Y hepaticojejunostomy is the procedure of choice in the management of
      major BDIs as it is accompanied by satisfactory results.

PMID- 16447482
TI  - Spontaneous subcapsular splenic hematoma: a rare complication of pancreatitis.
AB  - Subcapsular hematoma of the spleen is a rare complication of pancreatitis despite
      its close proximity to the pancreas. Pancreatic pseudocyst involving the tail of
      the pancreas may erode into the splenic hilum causing hilar vessel bleeding with
      subcapsular dissection and hematoma formation. The management of such
      complication is still controversial. It has been suggested that most of these
      complications spontaneously regress and therefore can be managed conservatively.
      A case of spontaneous splenic subcapsular hematoma resulting from pancreatitis
      was managed conservatively with a good outcome.

PMID- 16447483
TI  - Thoracoscopic resection of a mediastinal intrathymic parathyroid adenoma.
AB  - Mediastinal parathyroid adenomas and thymomas can be resected via a transcervical
      approach, median sternotomy, or less invasive surgical option of video-assisted
      thoracoscopic resection and more recently by way of the da Vinci robot. We
      present a case of a mediastinal parathyroid adenoma in a 55-year-old female with
      primary hyperparathyroidism. MRI also confirmed a mediastinal adenoma localized
      on sestamibi scan. Significant laboratory values were elevated parathyroid
      hormone (PTH) of 171 pg/mL (normal range = 15 to 65 pg/mL) and calcium of 11.6
      mg/dL (normal range = 8.5 to 10.5 mg/dL). Inability to hyperextend her neck due
      to cervical fusion made the transcervical approach unfavorable. To avoid a median
      sternotomy, we performed thoracoscopic resection of the adenoma via the left
      chest with the patient in a right lateral decubitus position. Three ports were
      placed; two in the anterior axillary line in the 4th and 6th intercostal spaces
      and one in the midaxillary line in the 5th intercostal space. Initial
      intraoperative PTH measurement was 192.9 pg/mL, and after adenoma removal the PTH
      level fell to 9 pg/mL. She was discharged home on postoperative day 1 without
      complications. At 3 months postprocedure, she remains asymptomatic with PTH and
      calcium levels within normal range. The 4 g, 2.4 cm intrathymic parathyroid
      adenoma had no evidence of malignancy. Thoracoscopic resection of an intrathymic
      parathyroid adenoma, a safe and less morbid alternative to median sternotomy, is
      an option when the transcervical approach is not viable.

PMID- 16447484
TI  - Ruptured giant colonic diverticulum.
AB  - Giant colonic diverticulum (GCD) is a rare complication of diverticular disease
      with less than 150 cases reported in the English literature. The clinical
      presentation ranges from asymptomatic to that of an acute abdomen. In most cases,
      giant colonic diverticulum is found in the sigmoid colon. The ideal treatment is
      elective resection of the sigmoid colon with primary anastomosis. When the
      diverticulum presents with perforation or obstruction, however, the treatment is
      a sigmoid colectomy with diverting colostomy (Hartmann procedure).

PMID- 16447485
TI  - Blowdart injury resulting in Brown-Sequard plus syndrome.
AB  - This report presents an interesting and unusual case of an injury sustained from
      a blowgun dart. The dart penetrated zone 2 of the neck, resulting in a
      neurological deficit consistent with a variant of Brown-Sequard syndrome referred
      to as "Brown-Sequard plus syndrome."

PMID- 16447486
TI  - A rare case of classic biphasic pulmonary blastoma.
AB  - Biphasic pulmonary blastomas are rare tumors that together with pulmonary
      carcinosarcomas comprise less than 2 per cent of all lung neoplasms. They can be
      defined as tumors that are composed of an admixture of immature mesenchyme and
      epithelium and that recapitulate morphologically the embryonal structure of the
      lung. First described in 1945 by Barnett and Barnard, their existence is well
      documented although their occurrence is rare. We present a case of a 40-year-old
      Hispanic female that presented with a 2-month history of retrosternal and
      midepigastric pain. A GI etiology was initially treated unsuccessfully with
      antireflux medications. A chest radiograph showed a 4.6-cm mass in the right
      upper lobe of the lung, and computed tomography showed right apical bullous
      formation with no lymphadenopathy. Bronchoscopy revealed no endobronchial
      lesions, and biopsy was nondiagnostic. The histopathologic and immunophenotypic
      analysis of a right upper lobectomy specimen was diagnostic of classic biphasic
      pulmonary blastoma. The rarity of these tumors makes easy identification
      difficult. Immunohistochemical analysis must be used to arrive at the proper
      diagnosis. It is imperative that there be good communication between the surgeon
      and pathologist and that institutions have access to facilities with the ability
      of identifying these complex tumors.

PMID- 16447488
TI  - FAO address.

PMID- 16447487
TI  - Pancreatic mass of unusual etiology: case report of metastatic disease after a
      prolonged lag phase.
AB  - Although not a typical site, the pancreas does occasionally harbor metastatic
      disease. Management of these metastases differs from the management of
      conventional primary cancers. Our case is one of an 85-year-old female presenting
      with obstructive jaundice and whose workup revealed a pancreatic mass. Her past
      medical history included a mastectomy 14 years previous for invasive lobular
      carcinoma. She underwent celiotomy, and an intraoperative diagnosis of metastatic
      lobular carcinoma of the breast was made based on frozen section. Due to
      pulmonary metastasis and vascular infiltration, which precluded
      pancreatoduodenectomy, the patient underwent palliative bypass and fared well
      postoperatively. With more aggressive management of primary breast cancers in the
      past decade, isolated metastatic disease is of increasing concern and raises
      questions about surgical strategies to be implemented with these patients. For
      instance, should palliative treatment be considered or should a radical intention
      to cure procedure be performed despite the metastatic disease? Factors favoring
      radical procedures include prolonged lag phase between the primary and the
      recurrence; presence of well-differentiated tumors; and isolated metastatic
      disease. Primary lung and renal cancers metastasize more frequently than breast
      cancers do to the pancreas. Hence, existing literature has not clearly defined
      indications for radical treatment of metastatic breast cancers to the pancreas.
      Based on experiences with metastatic renal and lung cancers, one can reasonably
      infer that radical procedures performed on selected cases could possibly achieve
      a cure or prolonged disease-free survival. The key factor in determining whether
      the patient undergoes palliative versus radical treatment is a slow growth
      pattern of the tumor, characterized by a prolonged lag phase between the primary
      and the metastatic disease.

PMID- 16447489
TI  - Welcome speech.

PMID- 16447490
TI  - Avian influenza--past, present and future challenges.
AB  - Avian influenza (AI) is an OIE-listed disease that has become of great importance
      both for animal and for human health. The increased relevance of AI in the fields
      of animal and human health, has highlighted the lack of scientific information on
      several aspects of the disease; this has hampered the adequate management of some
      of the recent crises, thus resulting in millions of dead animals and concern over
      loss of human lives and over management of the pandemic potential. The present
      paper aims to identify areas of knowledge of veterinary competence that need to
      be explored to generate information to support the global AI crisis. Given the
      current situation, it is imperative that close collaboration is sought and
      achieved by public health officials involved in the veterinary and medical
      aspects of the disease. In fact, only through the exchange of data, experiences,
      views and information will it be possible to combat this zoonosis that represents
      a major threat to public health and animal well-being.

PMID- 16447491
TI  - Epidemiology and ecology of highly pathogenic avian influenza with particular
      emphasis on South East Asia.
AB  - Highly pathogenic avian influenza (HPAI) has been recognised as a serious viral
      disease of poultry since 1878. The number of recorded outbreaks of HPAI has
      increased globally in the past 10 years culminating in 2004 with the
      unprecedented outbreaks of H5N1 HPAI involving at least nine countries in East
      and South-East Asia. Apart from the geographical extent of these outbreaks and
      apparent rapid spread, this epidemic has a number of unique features, among which
      is the role that asymptomatic domestic waterfowl and more particularly free
      ranging ducks play in the transmission of highly pathogenic H5N1. Field
      epidemiological studies have been conducted by the Food and Agriculture
      Organization and several collaborative centres to explore the factors that could
      have led to a change from infection to the emergence of widespread disease in
      2003-2004 and 2005. Domestic waterfowl, specific farming practices and agro
      ecological environments have been identified to play a key role in the
      occurrence, maintenance and spread of HPAI. Although there are some questions
      that remain unanswered regarding the origins of the 2004 outbreaks, the current
      understanding of the ecology and epidemiology of the disease should now lead to
      the development of adapted targeted surveillance studies and control strategies.

PMID- 16447492
TI  - Ecology and epidemiology of avian influenza in North and South America.
AB  - Wild waterfowl and shorebirds are known to be the natural reservoir for influenza
      A viruses. Surveillance studies in waterfowl and shorebirds in North America show
      that influenza A viruses are repeatedly recovered from these birds. However, the
      virus recovery is influenced by geography, season, age and species of birds. In
      addition to the natural reservoir, the live-bird marketing system (LBMS) in
      certain regions of the United States has been recognized as a man-made reservoir
      of influenza viruses and has been linked to several outbreaks of low
      pathogenicity avian influenza (LPAI) in poultry. Outbreaks of LPAI in commercial
      poultry is attributed to movement of infected birds, dirty or improperly cleaned
      crates, and contaminated vehicles from the LBMS to poultry farms. However, in the
      majority of outbreaks in poultry, the source of infection is suspected to be wild
      aquatic birds or the source is unknown. Since 2002, three outbreaks of highly
      pathogenic avian influenza (HPAI) have occurred in the Americas; one each in
      Chile (H7N3), United States (H5N2), and Canada (H7N3). In each of these
      outbreaks, a precursor virus of low pathogenicity mutated to become highly
      pathogenic after circulating in poultry. The HPAI viruses recovered from the
      three outbreaks had unique molecular and phenotypic characteristics that do not
      conform to other known HPAI viruses. These findings emphasize the need for
      monitoring wild and domestic bird species for presence of influenza A viruses.

PMID- 16447493
TI  - Recent epidemiology and ecology of influenza A viruses in avian species in Europe
      and the Middle East.
AB  - There have been at least ten distinct outbreaks of LPAI or HPAI in poultry caused
      by H5 or H7 viruses in the last eight years in Europe and the Middle East. There
      appears to be an increased occurrence of such episodes consistent with global
      trends. As a result, surveillance systems have been enhanced to facilitate early
      detection of infection in poultry, together with active surveillance of wild bird
      populations. These complementary activities have resulted in the detection of a
      number of viruses in wild bird populations, including some with high genetic
      similarity to newly detected viruses in poultry, for example, H7N3 in Italy and
      H7N7 in the Netherlands. Furthermore, there is evidence for continued circulation
      of H5 and H7 viruses in wild Anseriformes, thereby presenting a real and current
      threat for the introduction of viruses to domestic poultry, especially those
      reared in outdoor production systems. Viruses of H9N2 subtype continue to
      circulate widely in the Middle East and are associated with significant disease
      problems in poultry. The epidemiology has the potential to be complicated further
      by introduction of novel viruses through illegal importation of captive birds,
      such as was detected with H5N1 in Belgium in 2004. Continual genetic exchange in
      the avian virus gene pool and independent evolution of all gene segments either
      within an individual host species or among wild bird hosts suggests that these
      viruses are not in evolutionary stasis in the natural reservoir.

PMID- 16447494
TI  - Ecology and epidemiology of avian influenza in ostriches.
AB  - Avian influenza is important because of its potential devastating effect on
      poultry health and trade. The ostrich industry of South Africa has not escaped
      the consequences of control and export restrictions resulting from notifiable
      virus infections. Ostrich farmers first observed a syndrome of green urine in the
      early and mid 1980s. An H7N1 subtype, causing high mortality in young ostriches
      but with a low pathogenicity index for chickens, was first isolated in 1991. The
      first highly pathogenic subtype affecting ratites was reported during the 2000
      epidemic of H7N1 in Italy. Low pathogenic subtypes were isolated in South Africa
      from 1991 to 2004, with one HPAI isolated in 2004. International research work on
      ostriches with both H5 and H7 subtypes, in both low and high pathogenic
      pathotypes, found the severity of clinical disease was not directly correlated to
      the pathotype. The ecology and epidemiology of infections in ostriches is not
      well understood. Surveys suggest local migratory water birds may play an
      important role. They have direct contact with ostrich flocks through the free
      range production systems. Seasonal occurrence is seen, with the wet colder months
      more favourable for virus survival and detection. Management, population density,
      immune status and age are other important determinants of the severity of
      disease. Surveillance and monitoring must be implemented to understand the
      ecology and epidemiology, which extends to the validation and standardisation of
      diagnostic and serological methods for ostriches. Serious consideration should be
      given to vaccination, education and the use of separate production zones as part
      of a control programme.

PMID- 16447495
TI  - Pathogenicity of avian influenza viruses in poultry.
AB  - Historically, the pathogenicity of avian influenza (AI) viruses has been based on
      lethality for the major domesticated poultry species, the chicken. All AI viruses
      are categorised as either low (LP) and high pathogenicity (HP), but, within each
      category, pathobiological changes vary with host species and virus strain.
      Typically, AI viruses that are HP produce a similar severe, systemic disease with
      high mortality in chickens and a similar pathobiology in other galliforme birds,
      but usually either produce no infection or mild disease in ducks. The newer H5
      and the H7 HPAI viruses have shifted to increased virulence for chickens as
      evidenced by shorter mean death times (MDT). Furthermore, the Asia H5N1 HPAI
      viruses have changed from producing inconsistent respiratory infections in ducks
      to some strains being HP (Hong Kong 2002 viruses) with virus in internal organs
      and brain, and excretion of large virus quantities from respiratory, and to a
      lesser extent, intestinal tracts. However, the quantities of virus shed per bird
      are still 1 % of that produced in chickens. With 2003-2004 Asian H5N1 AI viruses,
      the isolates have been highly lethal for young ducks but this virulence is age
      dependent. Across all bird species, the ability to produce severe disease and
      death is associated with high virus replication titres in the host, especially in
      specific tissues such as brain and heart.

PMID- 16447496
TI  - Library of influenza virus strains for vaccine and diagnostic use against highly
      pathogenic avian influenza and human pandemics.
AB  - To prepare for the emergence of pandemic influenza in birds and mammals including
      humans, we have carried out global surveillance of avian influenza. Influenza A
      viruses of 48 combinations of 15 HA and 9 NA subtypes out of 135 theoretical
      combinations have been isolated from faecal samples of ducks in Alaska, Siberia,
      Mongolia, Taiwan, China and Japan. So far, viruses of 73 other combinations have
      been generated by genetic reassortment in chicken embryos. Thus, avian influenza
      viruses of 121 combinations of HA and NA subtypes have been stocked for use in
      vaccine and diagnosis. Their pathogenicity, antigenicity, genetic information,
      and yield in chicken embryo have been analysed and registered in the database.

PMID- 16447497
TI  - Avian influenza viruses and human health.
AB  - Influenza A viruses cause natural infections of humans, some other mammals and
      birds. Few of the 16 haemagglutinin and nine neuraminidase subtype combinations
      have been isolated from mammals, but all subtypes have been isolated from birds.
      In the 20th century, there were four pandemics of influenza as a result of the
      emergence of antigenically different strains in humans: 1918 (H1N1), 1957 (H2N2),
      1968 (H3N2) and 1977 (H1N1). Influenza A viruses contain eight distinct RNA genes
      and reassortment of these can occur in mixed infections with different viruses.
      The 1957 and 1968 pandemic viruses differed from the preceding viruses in humans
      by the substitution of genes that came from avian viruses, suggesting they arose
      by genetic reassortment of viruses of human and avian origin. Up to 1995, there
      had been only three reports of avian influenza viruses infecting humans, in 1959,
      1977 and 1981 (all H7N7), but, since 1996, there have been regular reports of
      natural infections of humans with avian influenza viruses: in England in 1996
      (H7N7), Hong Kong 1997 (H5N1), 1999 (H9N2), and 2003 (H5N1), in The Netherlands
      2003 (H7N7), Canada 2004 (H7N3), Vietnam 2004 (H5N1) and Thailand 2004 (H5N1).
      The H5N1 virus is alarming because 51 (64 %) of the 80 people confirmed as
      infected since 1997 have died.

PMID- 16447498
TI  - Occupational and consumer risks from avian influenza viruses.
AB  - Sporadic human infections have been reported with a few select avian influenza
      (AI) viruses over the past 50 years. Most of the infections resulted from the
      H7N7 high pathogenicity AI (HPAI) virus from The Netherlands (2003) and H5N1 HPAI
      viruses from several Asian countries (1997-2005). Epidemiological studies have
      identified direct exposure to infected poultry as the primary risk factor for
      human infection. In The Netherlands, veterinarians, cullers and poultry farmers
      had an occupational risk of infection through exposure to infected commercial
      poultry, and presented with conjunctivitis and/or influenza-like illnesses. In
      Asia, most of the clinical infections involved direct exposure to poultry in the
      smallholder sector or live poultry markets, and not commercial poultry. However,
      serological data from Hong Kong during 1997 indicated H5N1 infections without
      clinical disease were associated with occupational exposure. No cases of human AI
      infection have been linked to consumption of infected or contaminated poultry
      products. However, HPAI virus can be present in blood, bone and meat of infected
      poultry, which, if consumed raw, are a potential source of virus for human
      infections. Cooking and pasteurisation are effective methods of killing AI
      viruses. Proper vaccination of poultry has been shown to prevent HPAI virus from
      localising in the meat.

PMID- 16447499
TI  - Advances in molecular diagnostics for avian influenza.
AB  - Recent outbreaks of avian influenza (AI) have highlighted the necessity to
      improve existing tests and to develop new methods, in order to detect spread or
      new outbreaks more quickly, which is vital for the early and successful
      implementation of control strategies. Conventionally, the time between clinical
      suspicion and laboratory confirmation of AI can be relatively long because of the
      logistics of sending samples to laboratories and their capacity for providing
      high throughput of sensitive and specific assays. Increasingly, new-generation
      assays based on molecular diagnostics have become available and applied
      successfully to disease investigation or active surveillance programmes. There
      has been widespread application of techniques based on the amplification of
      specific nucleic acid sequences by polymerase chain reaction (PCR), ligase chain
      reaction and nucleic acid sequence-based amplification (NASBA). The approaches
      generally offer high specificity and sensitivity. One of the most promising
      technologies is real-time PCR, which enables amplification of nucleic acids and
      detection of the amplified products through specific probes at the same time. A
      rapid diagnosis can be achieved, together with potential for high throughput
      resulting from process automation. Currently, microarray technology is developing
      rapidly and has been applied to diagnosis of influenza A virus but generally
      lacks the necessary sensitivity for direct application to clinical specimens. In
      addition, these new technologies have been increasingly applied to rapid and
      reliable subtyping of AI viruses. The application of molecular technologies to
      the "field" is now potentially an option, through the availability of portable
      machines for conducting such tests, with prospects for radically changing
      diagnostic approaches for AI in the future.

PMID- 16447500
TI  - Molecular diagnosis of avian influenza during an outbreak.
AB  - Virus isolation (VI) in specific-pathogen-free (SPF) embryonated eggs or cell
      cultures is traditionally considered the method of choice for the detection and
      identification of avian influenza (AI) viruses. However, its value is limited
      because it is time-consuming and not cost-effective. AI is a highly contagious
      disease, able to spread in a susceptible population in a short period of time.
      Therefore, the prompt identification of an infected flock is crucial for control
      and eradication purposes. During an AI outbreak, the sample processing times
      using the above mentioned methods are often not compatible with the demands of
      the poultry industry. In addition, the delay in moving birds from a premises,
      whilst awaiting the VI result, often results in animal welfare issues. For this
      reason, when dealing with an epidemic of AI, rapid and reliable laboratory tests,
      such as RT-PCR and real-time PCR, should be available to reveal direct evidence
      of infection in the flocks. Scientific reports have been published in the recent
      past, evaluating their use during AI monitoring and surveillance programmes and
      epidemics. Based on the available information, the advantages and limits
      concerning the application of molecular methods during AI outbreaks are discussed
      in this paper.

PMID- 16447501
TI  - Control of avian influenza in Italy: from stamping out to emergency and
      prophylactic vaccination.
AB  - Since 1997, north-eastern Italy has been repeatedly challenged by avian influenza
      (AI) infections caused by viruses of the H5 and H7 subtypes. The penetration of
      such infections in the industrial circuit in densely populated poultry areas
      (DPPAs) resulted in massive spread, and early attempts to control AI only by
      stamping-out and restriction policies resulted in death or culling of millions of
      birds. The re-emergence or the introduction of AI viruses in the same DPPA
      resulted in the development of an emergency vaccination programme based on the
      use of heterologous vaccination and a companion discriminatory test. By enabling
      the detection of field exposure in vaccinated animals, the application of this
      system, in conjunction with a monitoring programme and a well-defined territorial
      strategy has resulted in the eradication of H7N1 and H7N3 epidemics that occurred
      between 2000 and 2004. Retrospective analysis of the AI outbreaks in north
      eastern Italy coupled with surveillance programmes in wild birds and in hobby
      flocks indicating that certain areas are at continuous high risk of infection,
      was the rationale for developing and implementing a bivalent H5/H7 pilot
      vaccination programme in a restricted area of the DPPA. Laboratory and field
      evidence indicate that vaccinated animals are more resistant to challenge and
      shed lower amounts of virus, thus acting as a tool for both prevention and
      control, thus limiting the impact of AI infections.

PMID- 16447502
TI  - Avian influenza vaccination in North America: strategies and difficulties.
AB  - Vaccination with high quality efficacious vaccines that are properly delivered
      can contribute to the control of avian influenza (AI) outbreaks when used as part
      of a comprehensive control programme that includes quarantines, animal movement
      controls, increased biosecurity, enhanced surveillance, and education. In North
      America both whole virus killed adjuvanted vaccines and fowlpox recombinant
      vaccines have been used to aid in the control of AI. The fowlpox recombinant
      vaccine is licensed in several countries including the United States (U.S.), but
      it has only been used in the field in Mexico and some Central American countries.
      The U.S., however, has considerable experience with the use of killed vaccines,
      primarily in turkeys. In the state of Minnesota in the 1980s and early 1990s,
      outbreaks of AI in range-reared turkeys were common, and vaccines were used
      successfully as part of a controlled marketing programme. More recently, several
      large layer flocks in Connecticut were vaccinated as an alternative to immediate
      depopulation after an H7N2 low pathogenic AI outbreak. The vaccinated flocks were
      intensively monitored for virus shed using sentinel birds, dead bird testing, and
      eventually some serological surveillance using a neuraminidase DIVA
      (differentiation of infected from vaccinated animal) approach. With these
      successes, vaccination is being considered as a valuable tool in comprehensive AI
      control strategies. Consideration for matching the vaccine to the field strain
      should also be considered to provide optimal protection including reduced
      shedding of virus. Antigenic drift of AI viruses after extended vaccination
      programmes has been observed in chickens, similar to what has been observed with
      human influenza viruses. Therefore, periodical evaluation of the vaccine to the
      field strain is necessary to maintain good protection from clinical disease and
      virus shedding.

PMID- 16447503
TI  - Development of a recombinant fowlpox virus vector-based vaccine of H5N1 subtype
      avian influenza.
AB  - The genetic stability of the recombinant fowlpox virus (named rFPV-HA-NA) was
      confirmed by serial passage on chicken embryo fibroblast (CEF) cells. The immune
      efficacy, safety, the minimum immunising dose, the time of immunity induced and
      the immune duration of the vector-based vaccine was evaluated in specific
      pathogen-free (SPF) chickens. The recombinant virus vaccine containing 100 plaque
      form units (PFU) could induce complete protection against challenge with H5N1
      highly pathogenic avian influenza virus (HPAIV). The immune efficacy, protecting
      chickens from clinical signs and death after challenge, was obtained one week
      after the immunisation with this vaccine. Protective immunity could last for 40
      weeks post-immunisation. So the recombinant fowlpox vaccine is a safe and highly
      effective gene engineering vaccine candidate, and will be used to prevent H5
      subtype avian influenza in the future.

PMID- 16447504
TI  - Use of avian influenza vaccination in Hong Kong.
AB  - Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong
      Kong up until February/March 2002 were controlled by stamping out. With endemic
      presence of the virus in the region and large daily importation of poultry to
      Hong Kong, the Administration considered that further risk management measures,
      in addition to improved biosecurity and enhanced surveillance, were necessary to
      prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a
      12-month period in the district with the last HPAI cases in the early 2002
      outbreak. The vaccination trial showed that farmer-administered killed H5N2
      vaccine produced suitable flock antibody responses; vaccinated birds were
      protected against H5N1 HPAI virus challenge and excreted significantly less H5N1
      virus; and vaccination was able to control virus excretion in flocks during field
      outbreaks. Universal vaccination of local chicken farms was introduced in June
      2003 and by the end of 2003 all chickens entering the live poultry markets in
      Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an
      enhanced biosecurity programme on farms and in live poultry markets and a
      comprehensive surveillance programme in poultry, wild birds, recreation park
      birds and pet birds were in place. Vaccination use and performance is closely
      monitored. This programme was successful in protecting local farms and live
      poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.

PMID- 16447505
TI  - Use of strategic vaccination for the control of avian influenza in Pakistan.
AB  - The first outbreak of highly pathogenic avian influenza (HPAI) virus caused by
      subtype H7N3 appeared in Pakistan in 1995. A homologous aqueous-based vaccine
      prepared from the field isolate employed as ring vaccination around the epicentre
      of the outbreak helped in controlling the disease. Later, in 1998, an outbreak of
      avian influenza virus (AIV) subtype H9N2, particularly affecting the broilers and
      broiler-breeders, was dealt with using the same vaccination approach. However,
      this time, the virus could not be successfully contained in the affected areas.
      Later on, low pathogenic avian influenza (LPAI) virus subtype H7N3 re-emerged in
      the broiler-breeder flocks in different poultry estates of the northern area of
      the country during 2000. This prompted the introduction of a vaccine strategy,
      whereby both aqueous and oil emulsion vaccines were routinely employed in and
      around the affected areas. This helped in the control of disease in this region.
      However, no AI monitoring and control strategy could be launched on a sustainable
      basis in these areas. In November 2003, new outbreaks of HPAI subtype H7N3
      occurred specifically in commercial layers in the southern part of the country,
      which were never vaccinated against AI in the past. In many cases, subtype H9N2
      was also recovered from the diseased flocks, with or without the presence of
      subtype H7N3. The disease caused heavy losses in the south. An emergency plan to
      control this outbreak was developed with the help of FAO in this regard. Under
      this plan, a nationwide AIV monitoring and vaccination strategy was developed.
      This paper discusses the role of vaccine type and vaccination schedule in the
      control of HPAI in this country.

PMID- 16447506
TI  - Making avian influenza vaccines available, an industry point of view (IFAH).
AB  - Vaccination against avian influenza (AI) has proved to be an efficient tool in
      the reduction of virus excretion and in increasing the threshold for infection.
      Vaccination in outbreaks, as part of a complete programme, has proved to be an
      essential component of control and eradication programmes. Avian influenza is a
      serious threat to public health. In contingency plans for outbreaks of highly
      pathogenic AI (HPAI), the option of emergency vaccination, using inactivated or
      recombinant vaccines, should be considered. The availability of suitable vaccines
      has to be ensured in 'peace time' in a contract for a vaccine or antigen bank.
      Unlike the human influenza vaccines, poultry AI vaccines have proved to provide
      protection against a wide range of strains within the same H-subtype. However, in
      case new H5 or H7 strains emerge in poultry, there is no regulatory guideline to
      support a swift reaction by the vaccine industry. Production of HPAI virus should
      take place in facilities with a Biosafety Level 3 (BSL3) to safeguard containment
      of virus and to prevent infection of manufacturing staff. Vaccine strains for
      inactivated vaccines should preferably be low pathogenicity AI (LPAI). In a new
      outbreak, it is essential to determine early which vaccine strain will provide
      protection against the field virus. Sequencing does not predict the protective
      capacity of vaccines. Challenge studies, providing essential information, take
      too much time and can be carried out only in BSL3 facilities. Serological
      matching of vaccine and field strains would provide a faster system. It is
      recommended that a matching system be developed and validated.

PMID- 16447507
TI  - OIE laboratory standards for avian influenza.
AB  - The principles are outlined by which the Office International des Epizooties
      (OIE) recognises diagnostic laboratory test procedures, based on the validation
      data and the fitness for purpose of any given test. The latest proposals for a
      definition of notifiable avian influenza are described, together with the place
      of vaccination, as part of the effort to control influenza in domestic poultry.

PMID- 16447508
TI  - Surveillance and compartmentalisation as a tool to control avian influenza.
AB  - Surveillance for avian influenza can have several objectives. Generally, these
      are to detect the presence of infection or to declare disease freedom. Claims for
      disease freedom can refer to an entire country, a zone within a country, or a
      compartment. Disease freedom cannot be demonstrated absolutely; however, through
      a multi-pronged approach employing different surveillance strategies, sufficient
      confidence in the absence of infection can be achieved. The recently developed
      OIE guidelines for surveillance for avian influenza offer different approaches to
      meet these goals. The guidelines are not intended to be prescriptive but rather
      offer options that countries may apply depending on their epidemiological
      situation. Compartmentalisation is a new concept that allows the recognition of
      populations of different health status based on management as opposed to
      geographic factors (regionalisation). A proposed approach for the application of
      this novel concept is presented.

PMID- 16447509
TI  - Social, economic and policy issues in the long-term control of HPAI.
AB  - Prevention and control of HPAI in Asia is a long term problem with important
      economic and policy consequences. The macro level impact of a single national
      outbreak is greatest for an exporting country, ranging in 2003-5 from dollars 65
      million to over dollars 400 million. No estimates are available for the impact of
      market disruption if endemic disease changes the pattern of regional and
      international trade. In countries with minimal exports, the total financial
      impact may be much smaller, but there can be serious losses to vulnerable sectors
      of society at several stages of the market chain. The economies of the region are
      growing and some countries could finance recurrent costs of AI control, but
      substantial investment in veterinary services is required. National and regional
      financing structures need to be reviewed. AI control strategies should include a
      broad financial support system that addresses education, credit, compensation and
      social relief programmes. Some strategies may result in restructuring of the
      industry, or affect the wider development of rural areas and local food security.

PMID- 16447510
TI  - Recommendations.

PMID- 16447511
TI  - Phylogenetic analyses of genes from South African LPAI viruses isolated in 2004
      from wild aquatic birds suggests introduction by Eurasian migrants.
AB  - In 2004, South Africa experienced its first recorded outbreak of a highly
      pathogenic notifiable avian influenza (HPNAI) viral strain of the H5N2 subtype in
      ostriches in the Eastern Cape province. The traditional ostrich-farming areas in
      the Western Cape province report almost yearly outbreaks of low pathogenicity
      avian influenza (LPAI) in ostriches, which is attributed to introduction by wild
      birds and certain climatic patterns. During the winter of 2004, LPAI H3N8, H4N8,
      H5N2 and H5N1 avian influenza viruses were isolated from wild aquatic birds. All
      eight genes of the H3N8, H4N8 and H5N1 viruses were analysed. The results show
      that the H5N1 virus does not belong to the HPAI Z/Z+N genotype currently
      circulating in Asia, but that the most recent common ancestors are Russian H5N2
      and H5N3 viruses. The N1 gene lacks the stalk deletion associated with virulence.
      Internal genes probably originate from a pool containing Chinese, Middle Eastern
      and Italian viruses. The South African H3N8 and H4N8 viruses appear to have
      derived their genes from an ecosystem where Asian H5N1, H6N9 and H9N2, Russian
      H4, and Danish H3N8 viruses have been circulating since 1997. All three viruses
      share recent nucleoprotein common ancestors with the German and Dutch HPNAI H7N7
      viruses from 2003. The diverse pool of genes from which local viruses are derived
      suggests that reassortment occurred at the Siberian breeding grounds where
      migratory paths cross, or within the South African ecosystem. This data
      highlights the importance of surveillance in aquatic migratory birds,
      particularly members of the Charadriidae, for their potential roles in the
      introduction of avian diseases to South African poultry and especially ostriches
      in the case of avian influenza.

PMID- 16447512
TI  - Ecology and molecular epidemiology of H9N2 avian influenza viruses isolated in
      Israel during 2000-2004 epizootic.
AB  - The first two isolates of H9N2 influenza virus were picked up from turkey and
      chicken hosts in May 2000, but the actual epizootic of the low pathogenicity
      avian influenza (LPAI) H9N2 virus started in December 2001, following a 1.5-year
      period of silence, during which the H10N7 and H6N3 influenza viruses were
      isolated sporadically. The outbreak of the H9N2 influenza began in northern
      Israel, from where the epizootic spread all over the country. Damage was
      relatively limited because of the widespread use of an inactivated vaccine.
      Single isolates were recorded in commercial ostrich and goose flocks, and in a
      wild pigeon. Apart from the routine serological tests, the diagnostics used the
      RT-PCR (reverse transcription polymerase chain reaction) test with type-specific
      primers related to the M and nucleoprotein (NP) genes, and a set of subtype
      specific primers related to all the haemagglutinin (HA) and neuraminidase (NA)
      subtypes. All the primers were specially constructed. The part coding for N
      terminus of the H chain of the HA gene of 61 out of 400 isolates was sequenced.
      The isolates showed a high rate of mutability, and differed distinctly from the
      H9 prototype strain; they belong to the same phylogenetic lineage divided into
      three sublineages, one of which exhibited a unique cleavage-site motif RSKR. The
      result indicates that two parallel evolutionary trends originated from the same
      local "prototype" isolate.

PMID- 16447513
TI  - HPAI surveillance programme in Cambodia: results and perspectives.
AB  - Cambodia has faced 15 confirmed highly pathogenic avian influenza (H5N1)
      outbreaks in different sectors of the poultry industry since January 2004. The
      country has very limited human and financial resources and, when the outbreak
      first began, the veterinary services were not equipped with the basic tools to
      collect accurate epidemiological information or to fight the disease. Therefore,
      different agencies, under the umbrella of the Food and Agriculture Organisation,
      are providing support to the Government to strengthen its capacity to diagnose,
      survey and control the avian influenza (AI) virus. Different surveillance tools
      are being tested, such as market monitoring and a sentinel villages' network, to
      offset the weakness of the national passive surveillance network. Several
      constraints were identified during the implementation of this programme, such as
      a lack of motivation among provincial staff, the limited capacity of the central
      team to compile and analyse the data generated, the reluctance of farmers to have
      their animals sampled, and weak diagnostic capacities. The sustainability of such
      a surveillance system once international support ends remains to be seen.
      Participatory epidemiology (PE) may be an appropriate complementary tool to track
      diseases. PE works on the principle that livestock keepers often possess detailed
      knowledge of animal diseases and can provide valuable diagnostics that could help
      in identifying AI outbreaks, particularly in remote areas.

PMID- 16447514
TI  - Shame, slap jack, and families that should lie.

PMID- 16447515
TI  - The District of Columbia amends its Health-Care Decisions Act: bioethics
      committees in the arena of public policy.

PMID- 16447516
TI  - Families and bioethics: old problems, new themes.

PMID- 16447517
TI  - Voice: cognitive impairment and medical decision making.

PMID- 16447518
TI  - On the mend: Alzheimer's and family caregiving.

PMID- 16447519
TI  - Imaginary fathers: a sentimental perspective on the question of identifying sperm
      donors.

PMID- 16447520
TI  - Like a motherless child: fetal eggs and families.

PMID- 16447521
TI  - Families and futility: forestalling demands for futile treatment.

PMID- 16447522
TI  - Practicing physicians and the role of family surrogate decision making.

PMID- 16447523
TI  - The state of research ethics: a tribute to John C. Fletcher.

PMID- 16447524
TI  - Informed consent: an end or a means? A response to Miller and Moreno.

PMID- 16447525
TI  - Informed consent and the therapeutic misconception: clarifying the challenge.

PMID- 16447526
TI  - Response to F.G. Miller and J.D. Moreno, "the state of research ethics: a tribute
      to John C. Fletcher".

PMID- 16447527
TI  - Family presence during resuscitation.

PMID- 16447528
TI  - The challenge: balancing competency and error management.

PMID- 16447529
TI  - Developing leadership skills in critical care nurses: a case scenario--part one.
AB  - During a recent CACCN board meeting, directors were challenged with developing an
      approach to a difficult case scenario. In a situation where inappropriate
      communication toward a new nurse was observed and reported directly to the charge
      nurse, participants identified that before responding, the charge nurse should
      seek out additional information to identify the problems causing the behaviour.
      Possible core problems included lack of clarity around the roles and
      responsibilities, plus the lack of training on preceptorship and the principles
      of effective communication. Solutions are proposed, along with associated
      strengths, weaknesses and barriers to implementation. In summary, nurses have
      much to gain from augmenting their leadership skills.

PMID- 16447530
TI  - Developing leadership skills in critical care nurses: a case scenario--part two.
AB  - During a recent CACCN board meeting, directors were challenged with developing an
      approach to a difficult case scenario. In a situation in which a group of nurses
      have angered some of the other nurses who work in the same unit, the directors
      were asked to identify core problems and suggest possible solutions and potential
      barriers to this problem. The perception that patient care is hampered, poor
      morale and job satisfaction as well as the lack of leadership and poor
      communication were identified as the core problems in the scenario that was
      presented. A number of possible solutions and the associated strengths and
      weaknesses, as well as the barriers to implementing the solutions were
      identified. In summary, critical care nurses must continue to advocate and lead
      the way toward strong leadership, modeling of appropriate behaviour and effective
      communication--all of which contribute to stronger team development and,
      ultimately, result in better, safer patient care.

PMID- 16447531
TI  - J wave and hypothermia.
AB  - Hypothermia can result from exposure to a cold environment (e.g., accidental
      drowning) or it can be induced and used as a brain protection strategy (e.g.,
      therapeutic hypothermia). One common ECG presentation with hypothermia is the J
      wave, which is related to the altered cellular activities during hypothermia. A
      case study is used in this article to illustrate the presentation of a J wave
      with a patient experiencing hypothermia.

PMID- 16447533
TI  - The role of the critical care nurse in improving quality of life in ICU
      survivors.
AB  - In ICU survivors, QOL is a dynamic term that identifies to what extent a critical
      illness has affected one's life. As an outcome measure, QOL has been studied in
      ICU survivors over the last few years. Researchers suggest that QOL is poor
      following ICU admission, and identify specific QOL issues that ICU survivors deal
      with, mostly related to physical functioning. The critical care nurse's role is
      to better QOL by improving the ICU survivor's transition into the post-ICU period
      through improved mobility, good management of sedation, pain, sleep and, most
      importantly, discharge planning.

PMID- 16447532
TI  - A novel systematic approach to ECG interpretation.
AB  - Regardless of the patient's symptoms, the 12-lead electrocardiogram (ECG) needs
      to be assessed in a comprehensive and systematic manner in order to avoid missing
      critical information. The RIRI approach to ECG interpretation offers a fast,
      reliable and systematic method to ensure that all aspects of interpretation are
      covered. The acronym is easy to remember and can be used by all health care
      practitioners ranging from novice to expert. RIRI reminds us to check the rate,
      intervals, rhythm and ischemia/infarction. Becoming familiar with the RIRI
      approach and consistently using this method will reduce the amount of time spent
      on the interpretation of the ECG and increase the time spent with the patient.

PMID- 16447534
TI  - Oral and maxillofacial surgery.

PMID- 16447535
TI  - Overcoming the generational gap.

PMID- 16447536
TI  - Know the facts about fees.

PMID- 16447537
TI  - Historical perspective.

PMID- 16447538
TI  - Upstate is not an oasis.

PMID- 16447539
TI  - Forgotten population.

PMID- 16447540
TI  - A tool to be used wisely.

PMID- 16447541
TI  - A residency made me a better dentist.

PMID- 16447542
TI  - Evolution of a dental implant practice. The Camlog implant system.
AB  - After extensive experience with a variety of implant systems dating back to the
      late 1960s, the author has begun placing Camlog implants, developed by Dr. Axel
      Kirsch. The design of this system eliminates the risk of rotation and screw
      loosening, while at the same time offering extraordinary ease of use. The
      treatment of three patients with Camlog implants is described.

PMID- 16447543
TI  - Role of computerized tomography in management of impacted mandibular third
      molars.
AB  - Nerve injury following mandibular third molar (M3) removal is a rare but serious
      complication. The purpose of this article is to review the role of currently
      available imaging technologies to facilitate clinical decision-making in the
      setting of M3 surgery. Given findings suggestive of high risk for inferior
      alveolar nerve (IAN) injury, the clinician should consider additional imaging to
      assess better the anatomic relationship of the IAN and M3.

PMID- 16447544
TI  - Orofacial infections in the 21st century.
AB  - In the 21st century, most orofacial infections are routinely managed with proper
      clinical assessment, selective diagnostic imaging, appropriate antibiotic therapy
      and timely surgical intervention. A thorough understanding of contemporary
      microbiology, pharmacology and surgical anatomy will enable the clinician to
      minimize the morbidity and mortality of orofacial infections.

PMID- 16447545
TI  - Hugo Obwegeser: forty years later.

PMID- 16447546
TI  - Acronyms in dentistry: what do they mean?

PMID- 16447547
TI  - Dentistry's "hot" issues debated at ADA annual session.

PMID- 16447548
TI  - [Arterial and venous blood flow at different stages of vascular cognitive
      impairment].
AB  - Sixty-nine patients with vascular cognitive impairment (VCI) have been studied
      using complex assessment of clinical, cognitive, imaging and sonographic
      characteristics at different stages of the disease. The ratio of venous return
      from the brain to arterial inflow, an integral parameter of cerebral
      hemodynamics, has been also investigated. The results revealed that the most
      severe clinical, cognitive and imaging changes were typical for cases with
      disturbances of both arterial and venous cerebral blood flow. VCI progression was
      followed by the deterioration of cognitive and imaging characteristics. The
      advanced stage of VCI was featured by the most significant clinical, cognitive
      and imaging changes, on one hand, and moderate sonographic characteristics, on
      the other. Disorders of both arterial and venous cerebral blood flow components
      contribute to VCI pathogenesis.

PMID- 16447549
TI  - [Thrombolytic therapy: formation and current practice of intravenous thrombolysis
      in acute ischemic stroke].
AB  - The benefits and limitations of intravenous thrombolytic therapy using
      recombinant tissue plasminogen activator (alteplase) are discussed.
      Pathophysiological background of thrombolysis, its history and ways of clinical
      usage, the major clinical trials, assessing safety and efficacy of the method,
      and practical recommendations, are presented.

PMID- 16447550
TI  - [An experience of intra-arterial thrombolytic therapy of ischemic stroke in Uzbek
      republic center of emergency care].
AB  - Acute period of stroke is a crucial stage of the disease. The differential
      therapy in the first 3-6 h from the onset of acute ischemic stroke, so-called
      "therapeutic window", is of special importance. Obviously, favorable clinical
      outcome in such patients is largely depends on the early recanalization during
      "therapeutic window". Presented, are the results of intra-arterial thrombolysis
      in patients with ischemic stroke, which reveal its high therapeutic
      effectiveness. Though there was limited clinical evidence for a high effect of
      recanalization of intra-arterial thrombolysis, this approach opens new
      perspectives for large scale clinical investigations using endovascular methods
      in thrombolytic therapy of patients with ischemic stroke.

PMID- 16447551
TI  - [Clinico-neurological and stabilometric analysis of betahistine (betaserc)
      efficacy in the patients with vertigo in the rehabilitation period of ischemic
      stroke].
AB  - A study of betahistine (betaserc) in 65 patients aged 59,48 +/- 8,63 years with
      vertigo in early rehabilitation period of ischemic stroke has been carried out.
      Thirty-five patients got atiplatelet and antihypertensive therapy and were also
      treated by betaserc--8-16 mg 3 times per day for 14 days per os, after meals. The
      control group of 30 patients received only atiplatelet and antihypertensive
      therapy. Both groups were similar in demographic and clinical characteristics.
      The treatment with betahistine reduced the intensity and duration of vertigo, led
      to improvement of coordination and equilibrium, increase stability of a vertical
      posture that was accompanied by significant (p<0,05) improvement of the values on
      the Hoffenberth and Bohannon scales. Betahistine treatment also resulted in
      marked authentic (p<0,05) improvement of stabilometric parameters in biological
      feedback task that might be explained by activation of the mechanisms maintaining
      vertical balance. An improvement of clinical and neurophysiologic traits was more
      pronounced in the group treated with betaserc as compared to the control group.

PMID- 16447552
TI  - [Cognitive functions and emotional state of post stroke patients on
      antihypertensive therapy].
AB  - To normalize arterial pressure (AP), combined antihypertensive therapy, basing on
      intake of 2,5-5 mg cilazapril, inhibitor of angiotensin-converting enzyme (IACE),
      was administered to 22 patients, 12 men, 10 women, aged from 49 to 74 years, mean
      age 63 +/- 7 years, who survived stroke (18 patients) or transitory ischemic
      attack (3 patients). Magnetic resonance tomography (MRT), i.e. perfusion regime,
      neuropsychological study and assessment of emotional state (Beck depression
      inventory and Spilberger anxiety scale) were conducted before and at the end of
      the treatment. During 6 months therapy, systolic blood pressure decreased from
      154,7 +/- 12 to 128 +/- 23 mm HG and diastolic pressure from 90,3 +/- 9,6 to 79,4
      +/- 23 mm Hg in all patients, without side-effects and development of stroke.
      There were neither new foci registered by MRT, no significant changes of cerebral
      blood flow. At the end of the treatment, cognitive functions were improved on the
      Mini Mental State Examination, on short-term memory test, Boston naming test and
      Wisconsin Card Sorting Test but no changes were found in emotional state of
      patients.

PMID- 16447553
TI  - [Use of galidor in therapy of chronic brain ischemia].

PMID- 16447554
TI  - [Crioglobulinemia in cerebral and coronal atherothrombosis].
AB  - Forty-seven patients: group A--17 patients with acute ischemic atherothrombotic
      stroke and group B--30 patients with acute Q-formation myocardial infarction. The
      levels of dynamics and comparative clinical relevance of crioglobulinemia in
      patients of the both groups have been evaluated. Crioglobulines (CG) in the
      peripheral blood serum were determined at 1, 2, 3, 7th and 14th days after the
      disease development. On the 1st day, the elevated CG level similar in the both
      groups as well as similarity of crioglobulinemia dynamics in whole was observed.
      In the group A, but not in the group B, the CG level was directly correlated with
      disease severity (p<0,05). In the group B, there was a trend, which depended on
      the blood CG level on the 1st day of the disease and on the presence of previous
      stenocardia (p<0,1).

PMID- 16447555
TI  - [Complement componenets, C3 and factors B, in the blood of patients with acute
      ischemic stroke].
AB  - Several studies suggest that activation of compliment cascade contributes to the
      development of the inflammatory immune response in ischemic stroke and results in
      tissue injury by initiating apoptosis and necrosis. It is proposed that
      suppression of the compliment activation may have positive effect on stroke
      severity and outcome. However, the majority of data relevant to involvement of
      the compliment in the pathogenethic mechanisms of stroke have been obtained in
      animal models of stroke that does not allow to extrapolate these data to humans.
      Our previous studies were the first ones demonstrated the involvement of both the
      classical and the alternative complement activation pathways in the pathogenetic
      mechanisms of generation and development of stroke in humans. In the present
      work, using immunoblotting, we determined the levels of key components of the
      classical and alternative pathways of complement activation, C3 and factor B, in
      the blood of patients with ischemic stroke. Comparing to healthy controls,
      patients with ischemic stroke are characterized by the increased level of C3 and
      decreased level of factor B.

PMID- 16447556
TI  - [An influence of histochrome on the dynamics of neurological disorders and MRT
      picture in experimental hemorrhagic stroke].
AB  - Presented are the results of the use of histochrome in animals with experimental
      hemorrhagic stroke. An influence of the compound on cerebral edema and the
      dynamics of hemoglobulin converting as well as a role of MRT in diagnostic of
      experimental hemorrhagic stroke in different periods of the disease are
      discussed.

PMID- 16447557
TI  - [Stroke care profile: a study of Lithuania population in Kaunas].
AB  - An aim of the study was to evaluate volume of medical care for stroke patients in
      Kaunas, Lithuania. Patients with first-ever stroke admitted to 2 Kaunas municipal
      hospitals have been registered. Data have been collected according to the
      requirements of the EC BIOMED-2 Program "Towards cost-effective stroke care"
      using standardized questionnaires. In total 331 patients (121 men and 210 women,
      mean age 69,8 +/- 0,64 years) were studied, 52% being admitted to the hospital
      during the first 6 h of the illness and over two thirds during the first 24 h.
      Most of patients (85%) were hospitalized into general neurological wards.
      Computed tomography of the brain was performed in one third of the patients. More
      than two thirds did not undergo any of the possible neurodiagnostic procedures.
      During staying in the hospital, rehabilitation was launched for 53,2% of
      patients. Out of all patients survived (83,5%), 29,9% were discharged to the
      rehabilitation unit. The results revealed that the level of medical care for a
      stroke patient appeared to be rather moderate: delay time for hospital medical
      care was too long, proportion of diagnostic examinations was too low and the
      volume of rehabilitation and social services were not sufficient.

PMID- 16447558
TI  - [Ethnic and genealogical aspects of cerebral stroke in Izhevsk city].
AB  - To study hereditary predisposition to stroke in main ethnic groups of Izhevsk,
      210 patients born in ethnically homogenous marriages have been examined and the
      data on state of health of 1701 relatives over 40 years old have been obtained. A
      role of hereditary factor in development of stroke was revealed. Also, there were
      ethnic differences related to a prevalence of carbohydrate-lipid metabolism
      disorder in patients of the Tartar group comparing to Udmurt and Russians.

PMID- 16447559
TI  - [Aspirin and primary prevention of vascular diseases in women].

PMID- 16447560
TI  - [Typology of posttraumatic stress disorder in children and adolescents].
AB  - The results of clinical and psychopathological study of 161 patients with
      posttraumatic stress disorder (PTSD), aged 318 years, illness duration from 1
      month to 4 years, are presented. Four main clinical PTSD variants (types) have
      been singled out in children and adolescents: insomniac (34.8%), phobic (23.6%),
      psychopathic-like (21.7%) and asthenic-depressive (19.9%). These variants
      differed in the course and prognosis and their frequency depended on age and
      ethnicity of patients. No sex-dependent differences have been found.

PMID- 16447561
TI  - [The treatment of patients with toxic encephalopathy caused by using surrogate
      psychoactive manganese-containing compounds].
AB  - Toxic encephalopathy caused by using surrogate psychoactive manganese-containing
      compounds was characterized clinically by a combination of parkinsonian, dystonic
      and pseudobulbar syndromes, eye-movement disturbances, autonomic insufficiency,
      affective disorders and moderate intellectual and memory impairment.
      Pharmacotherapeutic efficacy of mexidol has been studied. The results of the
      study showed that mexidol therapeutic course has a moderate effect on the
      expression of movement disorders and intellectual and memory impairment. Mexidol
      treatment significantly reduced severity of affective disorders and improved
      quality of life and daily activity of patients.

PMID- 16447562
TI  - [The phenotropil treatment of the consequences of brain organic lesions].
AB  - Ninety-nine patients with encephalopathy developed in the remote period after
      acute lesions of cerebral blood circulation, brain traumas and cerebral gliomas
      surgery have been studied. Phenotropil was used in a dosage of 200 mg per day
      during one month. A CT survey revealed that in a stable state of brain changes
      phenotropil exerted the mostly pronounced influence on movement disturbances:
      decreased an extent of pareses in limb and face muscles, improved motor
      coordination, higher brain functions, memory, attention, counting. Patients
      exhibited higher mobility and daily activity, along with lower discomfort,
      anxiety and depression. EEG study showed more intensive alpha- and beta-rhythms,
      a decrease of paroxysmal activity and slow waves as well as a general tendency to
      its normalization.

PMID- 16447563
TI  - [Spinobulbospinal reflex activity of the brain stem in patients with chronic
      circulatory insufficiency].

PMID- 16447564
TI  - [Health-related quality of life in patients with multiple sclerosis].

PMID- 16447565
TI  - [The activity of Moscow Alexeev psychiatric hospital N1 during the Great
      Patriotic War (1941-1945)].

PMID- 16447566
TI  - [A combination of migraine and epilepsy].

PMID- 16447567
TI  - [Comorbidity of eating disorders and other impulse control disorders in anorexia
      nervosa].

PMID- 16447568
TI  - [The treatment of vascular disorders in Alzheimer's disease].

PMID- 16447569
TI  - [Pharmacoresistance in epilepsy].

PMID- 16447570
TI  - [Therapeutic monitoring of antiepileptic drugs].

PMID- 16447571
TI  - [Epilepsy, ion channels and genes].

PMID- 16447572
TI  - [A possibility of prevention and therapy of some nervous system disorders with
      physical factors caused by electronic paramagnetic resonance, nuclear magnetic
      resonance and nuclear gamma resonance methods of dialysis].

PMID- 16447573
TI  - [Present status of acute and urgent surgery].

PMID- 16447574
TI  - [Epidemiology of cleft disorders in East Slovakia].
AB  - Cleft lip and cleft palate are problems of great importance. The majority of
      cleft lips and palate are caused by the misdevelopment of mesoderm in facial
      region in second and third week of gestation. The main goal of the study was to
      evaluate the epidemiology of cleft lip and palate in East Slovakia and influence
      of environmental agents on the development of cleft lip and palate. The data were
      collected from epidemiological study performed by investigators among the
      population born with cleft anomaly in the period 1985-2000. Our conclusions
      concerning type of cleft and possible genetic and environmental influences were
      correlated to the literature. All of our results are pretty close to results
      published in literature.

PMID- 16447575
TI  - [Surgical management of varicose ulcers].
AB  - One of the most often diseases of the European population is the venous chronic
      leg ulcer. It requires a long-term and expensive therapy. Basic elements of the
      therapy are elastic banding of the leg, diuretics, antibiotics and local
      treatment. In some cases a profit can be acquired from surgical procedure, which
      includes the stripping and/or crossectomy of the saphenous vein or the subfascial
      ligation of insufficient perforators and skin grafting (two phases operation).
      This procedure shorts the time of therapy and prevents the ulcer recurrence,
      because it resolves the reason and the results of the disease. We present 22
      patients treated by this cure during the last 3 years at our surgery department
      of the 3rd faculty of medicine Charles University in Prague. 21 patients (95.5%)
      are healed.

PMID- 16447576
TI  - [Diverticulosis of the small intestine--the authors study group and a case
      review].
AB  - Our case review describes an unusual case of an acute GIT haemorrhaging, caused
      by multiple diverticulosis of the proximal jejunum. The disorder is rare, rarely
      reported in literature worldwide. The typical course of the disease is
      asymptomatic, manifesting itself late as acute complications, most commonly
      urgent abdominal disorders. Chronic symptoms are less frequent, e.g. unspecific
      abdominal pain or occult haemmorhage. Inspired by literature data, the authors
      set up their own group of patients, who had been operated by the team for
      diverticles located in the small intestine, in the last 9 years.

PMID- 16447577
TI  - [Resection of the pancreatic head and duodenum for the Crohn's disease of the
      duodenum].
AB  - The Crohn's disease rarely affects duodenum. The symptoms are unspecific and its
      diagnostic process may be difficult. Patients with complications-stenoses and
      fistules, are indicated for surgical treatment. According to literature, there is
      no straightforward agreement on the surgical treatment strategy. In most cases,
      non-resection procedures are indicated. The authors describe a case of a patient
      suffering from the Crohn's disease of his duodenum and chronic pancreatitis,
      which was managed using a radical procedure--hemipancreatoduodenectomy.

PMID- 16447578
TI  - [Open inguinal hernioplasty, comparison of various techniques--a pilot study].
AB  - The authors compare inguinal hemioplasties using a classical method, Lichtenstein
      method and PHS method from the point of view of a surgeon, as well as using
      subjective assessments by patients. Each group consists of 11 patients. The
      authors assess the following parameters: use of analgesics, duration of
      hospitalization, daily routine restriction and pain.

PMID- 16447579
TI  - [A case of strangulation ilieus of the ascending colon].
AB  - Authors present case of strangulation ileus of ascendent colon as a quite rare
      reason of bowel obstruction. Patient's clinical status has been affected by his
      social background. And they document importance of proper anamnesis and clinical
      examination in era of modern investigation methods that may be misinterpreted and
      entice surgeon from early operative intervention.

PMID- 16447580
TI  - [Volvulus of the lienal flexure of the colon].
AB  - The authors present the case-report of a 72-year-old man who was admitted to our
      clinic with acute abdomen symptoms and signs of acute peritonitis. The cause was
      rather rare diagnosis of left colon flexure volvulus. This find caused extensive
      gangrene of colon. Solution was subtotal colectomy, the patient is now 4 months
      after surgery in good shape.

PMID- 16447581
TI  - [Surgical management of advanced stages of rectal carcinomas].
AB  - The authors present a summary of literature data and their own experience with
      management of locally advanced rectal carcinomas. They prefer advanced surgical
      procedures, such as pelvic exenterations, and urge for preserving "quality of
      life".

PMID- 16447582
TI  - [Carcinoma of the pancreatic head and periampular carcinomas. 10-year results of
      their resection management].
AB  - INTRODUCTION: Parcial duodenopancreatectomy (DPE) remains the principal treatment
      method of carcinomas located in the region of the pancreatic head. Although
      several surgical clinics use this method, assessment of, mainly the long-term,
      treatment results is virtually absent in our literature. AIM: Presentation of
      early and late results of the procedure collected in a clinic, managing the
      procedures with "medium frequency". The study is aimed at patients with
      histologically confirmed carcinomas of the pancreatic head. MATERIAL AND METHODS:
      Prospective data from a group of patients who had undergone the DPE during the 10
      year study in the Surgical Clinic of the IInd Medical Faculty of the Charles
      University in Prague-Motol, have been collected. RESULTS: From January 1995 to
      the end of 2004, 121 DPEs were completed, the 30-day mortality rate was 4.9% and
      the morbidity rate reached 17.5%. The long-term results were assessed in 71
      cancer patients - the median survival rate was 18 months following the procedure
      (1-121 months), depending on the tumor type. CONCLUSIONS: The collected results
      are similar to those presented by foreign clinics (but conducted with lower
      frequencies here) and fall within a European better average.

PMID- 16447583
TI  - [Intususception of appendical cystadenoma imitating a caecal tumor].
AB  - Appendical cystadenoma is one of the histological forms of the appendical
      mucocele. Preoperative diagnostics is difficult, however, due to potential
      iatrogennic rupture during a surgical procedure, is very important. The authors
      present a case review of a 62-year-old patient with itususception of the
      appendical cystadenoma, until now rarely reported in literature. Upon the
      preoperative diagnosis the appendical cystadenoma appeared as a caecal tumor or a
      tumor of the terminal ileum. A histological, intraoperative, diagnosis was
      established, followed by a final histological examination of the resected tissue.
      The authors discuss contemporary options of the preoperative diagnostic measures
      of the appendical tumors, stressing up all risks of aspiration cytology as well
      as risks of laparoscopic approach in this pathology management

PMID- 16447584
TI  - [Severe necrotizing pancreatitis during pregnancy].
AB  - A case report of 28-year-old pregnant women (34 week of pregnancy) with acute
      pancreatitis is presented. Likely cause of pancreatitis in the patient was
      extreme combined hyperlipidemia. The subject underwent seven complicated
      surgeries and with a necessity of prolonged intensive post-operative care. A year
      apart from the episode of acute pancreatitis both the patient and her baby are
      doing well. Pancreatic function has been restored and plasma lipid levels are,
      with appropriate medication, within normal ranges. Analysis of the problematic
      the relationship between hypertriglyceridemia, pregnancy and acute pancreatitis.

PMID- 16447585
TI  - [Intestinal ischaemia--consequence of intestinal malrotation].
AB  - The subsets of acute intestinal ischaemia include mesenterica arterial occlusion,
      venous thrombosis and non-occlusive mesenteric ischaemia. Advances in
      pathophysiology, diagnosis and treatment, prognostic problems are associated
      still in mortality rates of more than 60%. Early diagnosis is the first in
      possibility for better prognosis. In our article is case one young man with acute
      non-occlusive intestinal ischaemia described, diagnosis and treatment. Mucosal
      surface necrosis and hemorrhage was supposed, sepsis was expected, mucosal
      regeneration after ten days surprising. While changes on the bowel were hard to
      decide to resection, there are bioptic picture of mucosal layer in the time
      described (Fig. 5-9). We have written about similar case of young man with
      Waldayer hernia in 1999.

PMID- 16447586
TI  - [Expense analysis of the proximal femoral fractures treatment].
AB  - The aim of this paper was to provide estimated average costs of the hip fractures
      in the national scale by means of the analysis of the treatment expenses of 256
      injured patients who were operated in the 1st Surgical Clinic of the General
      Teaching Hospital in Prague in 2002. Particular cost items as operation costs,
      price of the implant, hospitalization expenses by the categories and price of
      blood derivates were figured out. The follow-up treatment after hospital
      discharge like price per bed, expenses for general practicioner etc. was
      considered as well. Each patient was observed for the period of one year after
      the operation. As a result we came to the total sum of 120,000 Kc per one patient
      per year. The way to reduce hip fractures treatment cost does not certainly lead
      to deterioration of medical care quality but to proper treatment of osteoporosis
      which is the principal cause of these injuries.

PMID- 16447587
TI  - [Technology of future: Da Vinci robotic surgery].

PMID- 16447588
TI  - [Brief history of vesical lithiasis management].
AB  - Stones of the bladder are one of the oldest illness that we know. History of its
      treatment has been cause of discussion in different moments. Since first
      treatments in Egypt or India, until our extracorporeal shock waves lithotritia
      (ESWL), there have been many intermediate treatments. The objective of this work
      is to know a little about some of these advances and their authors, as well as
      the instruments that have made it possible.

PMID- 16447589
TI  - [Laparoscopic radical prostatectomy. Only at centers of expertise].
AB  - OBJECTIVES: To present and evaluate our experience and initial results in radical
      laparoscopic prostatectomy which we have been using for two and an half years in
      our General Hospital (covering a total population of 200.000 inhabitants).
      MATERIAL AND METHODS: Between December 2002 and August 2005, were selected 26
      patients for radical laparoscopic prostatectomy (25 transperitoneal and 1
      extraperitoneal). Mean age was 62.3 +/- 5.3 years (range 52-69). Mean PSA level
      was 9.16 +/- 4.20 ng/mL (range 5.26 to 24.3). Pre-operative classification was
      Tlc in 10 patients (38.4%), T2a in 8 (30.8%) and T2b in 8. Mean Gleason Score was
      6 +/- 0.8 (range 4-7). Three patients had undergone preoperatively neo-adjuvant
      hormonal blockage (11.5%). Simultaneous bilateral inguinal lymphadenectomy was
      performed in two patients. In no case did we consider a nerve sparing approach.
      RESULTS: The procedure was accomplished in 20 patients. Mean follow-up was 12.4
      +/- 8.6 months (range 3 - 34). There was no perioperative mortality. Conversion
      to open surgery was required six times in the ten first cases but not thereafter.
      Mean operating time for the whole series was 303 +/- 95 minutes (range 150-540)
      but with a distinct difference between the first fourteen and the last six cases:
      332 +/- 92.58 versus 236.6 +/- 66.5 (p<0.02). Mean blood loss was 90.25 +/- 46.5
      ml. There were early postoperative complications in 4 patients (15.38%). Final
      pathological staging was: T2a in three patients (15%), T2b (50%) in 10, T3a (15%)
      in three and T3b (20%) in four. Positive margins were found in three cases
      (11.5%): T2b, T3a and T3b. Mean hospitalisation time was 4.7 +/- 3.1 days.
      Provided there was no urinary leakage, the urinary catheter was removed at 12.7
      +/- 2.7 days. Full continence at three months was achieved in 17 of the patients
      (85%) who had undergone the full laparoscopic procedure. CONCLUSIONS: Our
      previous experience in other major laparoscopic procedures has allowed us to
      perform radical laparoscopic prostatectomy with a fast learning curve even in a
      setting of a relatively low population. Initial long term results seem similar to
      those achieved with conventional surgery.

PMID- 16447590
TI  - [Prostate cancer diagnosis using 24 cores extended biopsy].
AB  - OBJECTIVE: To determine the diagnostic performance of extended prostatic biopsy
      (PB) in prostate cancer (PC) and variables affecting positivity. MATERIALS AND
      METHODS: Patients (n = 147) underwent 24 cylinder PB at the Arquitecto Marcide
      Hospital, Ferrol, La Coruna, between December 2002-September 2004. Inclusion
      criteria were the following: patients aged < or = 70 with one or more negative PB
      or aged < or = 75 with two or more negative PB. An univariate analysis was
      carried out using the chi-squared test for the qualitative variables and the t
      Student and U Mann-Whitney tests in the case of the quantitative variables, plus
      a logistical regression analysis in order to identify those variables related to
      the extended PB positivity. RESULTS: 60 patients (40.82%) were identified as
      having PC. Significant differences were observed in prostatic volume, free/total
      PSA ratio in the initial PB, free/total PSA ratio in the extended PB, PSA-density
      in the extended PB as well as the existence of chronic prostatitis in previous
      PB. During the multivariate analysis it was found that the PSA-density and the
      presence of chronic prostatitis in previous PB independently predicted the
      positivity of the extended PB. CONCLUSIONS: Extended PB allows for the detection
      of PC in 40.82% of patients with previous negative PB. The increase in PSA
      density is associated with a greater probability of PC, whilst the existence of
      chronic prostatitis in prior PB significantly reduces the probability of PC in
      the extended PB.

PMID- 16447591
TI  - [Utility of local anesthesia of the periprostatic plexus in the control of the
      pain in the ultrasound-guided prostate biopsy].
AB  - OBJECTIVE: Periprostatic plexus anesthesia (PPA) is not current practice during
      prostate ultrasound-guided biopsy (PB). Many patients must undergo a second or
      more PB if a prostate carcinoma is suspected. Due to pain, many patients reject
      the procedure, or it has to be performed with general anesthesia. Our objective
      was to evaluate the utility of PPA to eliminate the pain caused by PB, as well as
      the acceptance of the procedure under these conditions. PATIENTS AND METHODS:
      Between october 2002 and june 2003 we designed a randomized prospective study
      with 275 patients that were seen in 2 different hospitals and required PB. In the
      1st group we included 101 males who underwent PB without PA. In the other group,
      174 male patients submitted PB after PPA were included. 10 cc lidocaine, 2%
      diluted 50% was injected with a 22g needle. At the end of the procedure, patients
      were asked to fill in a questionnaire about their satisfaction and degree of pain
      felt. RESULTS: In the second group of patients we obtained significantly inferior
      values (p < 0.005, IC 95%) in the quantitative evaluation of pain compared with
      the first group (1.24 +/- 0.4 vs. 2.5 +/- 1.1). Ask per the possibility of
      repeating PB if it were necessary, none of the patients in the 2nd group would
      object, whereas 10% in the 1st group would not have the biopsy repeated or would
      only accept it if it was done with general anesthesia. No complications due to
      PPA were found. CONCLUSION: PPA is a safe procedure that significantly reduces
      pain during PB, improving its acquiescence among patients.

PMID- 16447592
TI  - [Importance of heterotrimeric G proteins in prostate cancer molecular biology].
AB  - OBJECTIVE: To deep in the knowledge of the involvement of G-protein alphas and
      alphai subunits in human prostate cancer. METHODS: Prostate tissue from 9
      patients undergoing radical prostatectomy for prostate cancer and 5 controls
      undergoing cystoprostatectomy for bladder carcinoma. G-protein alphas and alphai
      subunits were studied for expression (mRNA by RT-PCR and protein by Western
      blot), functionality (adenylyl cyclase activity, AC) and possibility of mutations
      (analysis with restriction enzymes and cDNA sequentiation). RESULTS: At mRNA
      level, the expression of alphas, alphai1, alphai2 y alphai3 was detected in
      healthy and cancerous tissues. At protein level, the expression of alphas y
      alphai1,2 diminished (25% and 40%, respectively) in prostate cancer. The
      expression of alphai3/0 also diminished, whereas that of beta subunit was not
      modified. Basal AC activity in adenocarcinoma membranes was 40% inferior to the
      control. Digestion with restriction enzymes Eag I or AlwN I did not allow to
      locate mutations in alphas. However, digestion at alphai2 level with BstU I
      enzyme served to observe a change of Gln205 (CAG triplet) to Pro (CCG).
      CONCLUSIONS: The functionality and expression of heterotrimeric G proteins are
      selectively modified in human prostate adenocarcinoma, occurring in addition some
      punctual mutation. The observed substitution of Gln205 by Pro may result in a low
      GTPase activity for alphai2 that, therefore, is stabilized in its active form.

PMID- 16447593
TI  - [Transdermal iontophoresis with dexamethasone and verapamil for Peyronie's
      disease].
AB  - OBJECTIVES: To evaluate the effects of transdermal iontophoresis with verapamil
      and dexamethasone in patients with Peyronie's disease of less than one year of
      evolution. MATERIAL AND METHODS: We have treated ten patients twice a week during
      six consecutive weeks using iontophoresis with a Miniphysionizer dispositive.
      This device generates a 2mA electric current during 20 min which triggers the
      transdermal penetration of medication. In every session dexamethasone 8 mg and
      verapamil 5mg were administered inside a small self-adhesive receptacle on the
      penile skin overlying the fibrosis plaque. To evaluate the efficacy, penile
      curvature was measured by Kelami's test, while the plaque size was assessed by
      penile ultrasound. Other parameters like pain, erectile function and ability for
      vaginal intercourse were recorded using questionnaires. Safety parameters were
      also assessed during treatment. RESULTS: No improvement or progression in penile
      curvature was evidenced in any of the patients. The hardness of the plaque was
      reduced in 5 patients, becoming impalpable in 2 of them. Decrease in plaque
      volume was observed by penile ultrasound in 6. Pain improved in 8 patients,
      disappearing in 6 of them. One patient recovered his erectile function at the end
      of the treatment; whereas 3 referred that their ability for intercourse enhanced
      while 2 reported that treatment improved their sexual life in general. We didn't
      record any significantly side effects, except for a transitory and slight dermal
      redness on the site of electrode placement. CONCLUSIONS: Transdermal
      iontophoresis is an effective treatment for pain control in early stages of
      Peyronie's disease. Efficacy in reducing penile curvature seems to be limited.
      Controlled clinical trials are needed, and perhaps reviewing indications in order
      to obtain more relevant clinical effects.

PMID- 16447595
TI  - [Is necessary to practice orchiectomy in patients with post-puberal maldescended
      testes?].
AB  - OBJECTIVE: The cryptorchidism is a risk factor for testicular cancer and is
      associated with cancer in the contraleteral testicle. The mechanism that leads to
      an increased risk of causes in a cryptorchid testis is unclear. MATERIALS AND
      METHODS: We analyzed 25 patients of 20-years old for maldescended testicles we
      practiced orchiectomy in 22 testicles and orchiopexy in 7 testicles. The time
      patients had the testicles in an anomalous location were between 20-51 years.
      RESULTS: The elder patients with maldescends testicles came because the couldn't
      feel the testicle in the scrotum and the 16% of them because of infertility. Only
      1 of 25 cases (4%) were demonstrated cancer with pure seminoma. CONCLUSIONS: In
      the following up of the patients none of them presented contralateral testicle
      cancer between 5-10 years. The patients who were practiced the orchiopexy no-one
      presented testicular cancer between 5-11 years.

PMID- 16447594
TI  - [Priapism].
AB  - Priapism has been defined by AFUD as a pathological condition which consists in a
      penile erection that persists moreover or is not related to sexual stimulation.
      Priapism pathophysiology has remained unknown until differents groups of clinical
      investigators began to research about this entity in patients complaining of
      erectile dysfunction, who where receiving treatment with intracavernosal
      vasoactive molecules. Priapism can be clasified into ischaemic (venocclusive):
      the most prevalent type, or Arterial (non-ischaemic). The purpose of this
      revision is to update the pathophysiology of the two types of priapism and to
      create an algorithm of therapeutical and diagnostic approach.

PMID- 16447596
TI  - [Erectile dysfunction during isotretinoin therapy].
AB  - Isotretinoin is a very effective drug for the treatment of severe recalcitrant
      acne. However, it's use is associated with many side effects, sometimes is
      associated with the emergence of psychiatric symptoms. During of a prospective
      study to evaluate the efficacy and safety of isotretinoin in acne, six male
      patients, refer difficulties in maintaining adequate penile erection in
      association with clinical symptoms of depression. To our knowledge this is the
      first time that this side effect is reported, so the results suggest that further
      studies of it's use in similar patients are warranted.

PMID- 16447598
TI  - [Hematuria during pregnancy caused by bladder tumour. Report of 2 cases].
AB  - Tumours of the urinary bladder are rare in pregnancy. We report two such cases
      presenting with gross hematuria, but one of them was initially mistaken as
      vaginal bleeding. Patients age was 41 and 27 years old, at 26 and 18 weeks of
      gestation respectively. Diagnoses were made with cystoscopy and sonography.
      Tocolytics agents were employed. Both of the tumours were managed succesfully by
      transurethral electroresection. Raquianesthesia was employed in both. There were
      no adverse effects on the pregnacies. Transurethral resection is a safe procedure
      during pregnancy. The pathology diagnoses were inverted papilloma in the first
      case and papillary urothelial neoplasm of low malignant potential in the other
      one. The literature is reviewed.

PMID- 16447597
TI  - [Tension free monofilament polypropylene mesh in cystocele and rectocele
      concomitant repair].
AB  - OBJECTIVE: We presented our experience in the concomitant correction of cystocele
      and rectocele with polypropylene monofilament mesh (Gynemesh PS), with
      transvaginal free tension technique. METHOD: During 2004 correction was made in 7
      patients, Urogynecologic and Vaginal Surgery Unit of Gynecology and Obstetrics
      Department, Las Condes Clinic. Medium age 54 years old, weight 64 kgs. In four
      patients we used a third mesh for correction of urinary incontinence by TVT-O.
      RESULTS: They don't present intraoperative complications, neither in immediate or
      delayed postoperative time. We not observed hematoma, infection, erosion or
      exposition mesh. Cure of cystocele and rectocele was in the 100% of patients.
      Complications have not appeared, 4 cases completed three months of observation, 2
      cases two months and 1 case one month. DISCUSSION: The use of protesic
      polypropylene multifilament macropore mesh in the concomitant correction of
      cistocele and rectocele, by transvaginal route with tension free technique seems
      to be a safe and effective surgery procedure.

PMID- 16447599
TI  - [Solitary fibrous tumor of the prostate].
AB  - We report a new case of a solitary fibrous tumor. It is a tumor which involve to
      genitourinary system unusual time, and it is exceptional in the prostate. Our
      patient began with bladder compression symptoms. Radiological studies showed
      polilobed mass that moved out the bladder although the could not show the pelvic
      organ was involved. The definitive diagnosis was made by histology and
      inmunohistochemestry of the surgical piece.

PMID- 16447600
TI  - [Inverted papilloma of the bladder with recurrence in prostatic urethra].
AB  - Urothelial inverted papilloma is usually a solitary lesion with rare recurrences.
      Its behaviour is unclear, its potential for recurrence or progression is not well
      known. We present a case of inverted papilloma of the bladder with recurrence in
      prostatic urethra after four years of follow-up. We review etiology, clinical
      presentation, diagnose, treatment and the present discussion about its malignancy
      ability.

PMID- 16447601
TI  - [Renal cell carcinoma in crossed fused renal ectopia].
AB  - Crossed renal ectopia its a rare congenital malformation and in most cases it
      presents with fusion of both kidneys. Patients should be asynptomatic until 4a-5a
      decade and at that time they unfold urinary infection, urolithiasis, abdominal
      mass or pain that simulates a gastric disease. We report a case of renal cell
      carcinoma in a patient with crossed fused renal ectopia, showed in a Scan that
      was performed for gastric disease suspicion.

PMID- 16447602
TI  - [Valdivia supine position as the best option for percutaneous surgery of renal
      calculi in morbidly obese patients].
AB  - INTRODUCTION: Treatment of the morbidly obese patient with symptomatic renal
      calculi is an interesting urological challenge. Extracorporeal shock wave
      lithotripsy is frequently not possible for several reasons, and many urological
      centers match these patients as one of the residual indications for open surgery
      of kidney lithiasis. MATERIAL AND METHOD: Two patients with body mass index more
      than 50 k/m2 and symptomatic kidney stones were treated with percutaneous
      nephrolithotomy in the supine position described by Valdivia (slightly
      lateralized supine decubitus). Standard instrumentation for percutaneous surgery
      and the semi-rigid ureteroscopy were used, through an Amplatz sheath proximally
      transfixed with a polypropylene stitch, so to avoid its lost under the fatty
      skin. Both patients were rendered stone-free without significant morbidity.
      DISCUSSION: The advantages of Valdivia position in those patients are clear, both
      for the commodity of the surgical team, -because time may be spared and help
      needed to mobilized the patient is less-, as well as for what concerns to the
      anesthesia, because cardio-respiratory restrictions created by a general
      anesthesia in prone are greater and more severe in the obese patient. This
      position seems to be more suitable than other ones recommended for percutaneous
      nephrolithotomy in the obese patients, such as prone decubitus on a surgical
      saddle, or lateral decubitus position, that may compromise the radiological
      control of the operation.

PMID- 16447606
TI  - [The wrong diet].

PMID- 16447607
TI  - [Family oriented nursing in the Schoneberg-Steglitz Hospice, Berlin: "it is a
      long learning process"].

PMID- 16447608
TI  - [Family oriented nursing--theory-nursing practice-transfer: finding a new
      balance].

PMID- 16447609
TI  - [Literature analysis: how do nurses perceive the needs of patients?].

PMID- 16447610
TI  - [Biographical works in nursing: rediscovering resources].

PMID- 16447611
TI  - ["Dementia" as a topic in literature: through the text to the person].

PMID- 16447612
TI  - [Burden of caregivers of dementia patients: the type of nursing care plays a
      role].

PMID- 16447613
TI  - [Decubitus ulcer prevalence in Germany: new data, new knowledge].

PMID- 16447614
TI  - [Critical comment on nursing expert standards: meeting challenges to improve
      quality].
AB  - The German Network for the Development of Quality in Nursing (DNQP) has published
      so called nursing "expert standards" on selected nursing issues. These are
      developed by expert working groups based on the current evidence, subsequently
      consented, and Implemented exemplarily. The standards aim at securing a generally
      accepted quality level in nursing. Accordingly, they are already consulted as
      yardstick for quality inspections and legal judgement identification, making it
      even more important that they meet recognized criteria. Therefore, members of the
      nursing section of the German network for evidence-based medicine (DNEbM)
      critically appraised the standards. Aspects worth being discussed are: definition
      of the term "expert standard", consideration of internationally recognized
      criteria for the development ol Suidelines and transparency of methockilogy;
      professional foundation and differentiation of recommendations, access to the
      standards, implementation tools, authors' possible conflicts of interest, as well
      as regular revision of the standards. This statement intents tobe the basis for a
      discussion on the future development of justified and comprehensible quality
      levels in nursing in Germany.

PMID- 16447615
TI  - [Introduction of the Bohm nursing model: biography often establishes behavior].

PMID- 16447616
TI  - [Hygiene in nursing--7: targeted prevention of infection in nursing homes].

PMID- 16447617
TI  - [Nosocomial infections in nursing homes--1: The elderly are especially at risk].

PMID- 16447618
TI  - [Error management in hospitals and nursing facilities: together rather than
      against each other].

PMID- 16447619
TI  - [From case to case: Mrs. M. would like to go home].

PMID- 16447620
TI  - [To be on speaking terms: how to reach a satisfactory communication in nursing
      care].
AB  - Communication with patients and their relatives as well as with colleagues is an
      integrated part of nursing profession. In order to reach a satisfactory
      communication, nurses should be aware of some elementary psychological principles
      of social interaction. Prejudices, misunderstandings, stress, opposed characters
      and mentalities are often raising problems, which can only be overcome by one
      manner: to be on speaking terms. But how good are we in talking to and dealing
      with each other? What do patients require for their well-being besides an optimum
      medication? What is the impact of both human relations and social backgrounds on
      the process of convalescence? Discussing these questions and feasible answers,
      the conclusion has to be drawn, that there are indeed some options, which
      facilitate a satisfactory communication.

PMID- 16447621
TI  - [Light modulates the rhythm of circadian time].

PMID- 16447622
TI  - [Light and fertility].

PMID- 16447623
TI  - [Congenital and acquired blindness].

PMID- 16447624
TI  - [History of artificial light].

PMID- 16447625
TI  - [Illusion and illumination].

PMID- 16447626
TI  - [Doctor's lanterns and candles-in the footsteps of Konrad Reijo Waara].

PMID- 16447627
TI  - [Light and mood therapy].

PMID- 16447628
TI  - [Challenges in the psychiatric care of young people with self injurious
      behavior]].

PMID- 16447630
TI  - Stop dieting!

PMID- 16447629
TI  - [Importance of pH control of osteoclasts on bone resorption].

PMID- 16447631
TI  - [Hope to the cancer therapy: cancer stem cell].
AB  - Cancer stem cells are defined as rare cells in cancer tissues with indefinite
      potential for self-renewal that drives tumorigenesis. It was first extensively
      documented for leukaemia and multiple myeloma. It has also been found in solid
      cancers such as human breast cancer and nervous system tumors. Studies of cancer
      stem cell biology and mechanisms of tumorigenesis are lending insight into the
      origins of cancer and will ultimately yield new approaches to fight cancer.

PMID- 16447632
TI  - [Stem cell, the basis for tissue and organ reconstruction].
AB  - Seed cells are prerequisite for reconstruction of artificial tissues/organs by
      tissue engineering approach. It has been widely accepted that stem cells are the
      best candidate for tissue engineering. The successful repair of tissue damages
      with adult stem cell mediated tissue engineering therapy in both animal models
      and patients has demonstrated the feasibility of using this technique for
      tissue/organ regeneration. Further studies in allogeneic adult stem cells and the
      establishment of universal embryonic stem cells will be critical for the
      industrialization of tissue engineering in future.

PMID- 16447633
TI  - [In vitro differentiation of human bone marrow-derived mesenchymal stem cells
      into blood vessel endothelial cells].
AB  - OBJECTIVE: To study differentiation of human bone marrow-derived mesenchymal stem
      cells (BDMSC) into blood vessel endothelial cells for ideal cell origin of
      complex organ tissue engineering vascularization and injured tissue repairing by
      cell transplantation. METHOD: After different days of induction with vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 3D
      fibrin-gels and matrigel, BDMSC and angiogenesis were determined by the
      utilization of morphological observation, tissue section and CD34, CD31, vascular
      endothelial growth factor receptor-1 (VEGFR-1, Flt-1), VEGFR-2 (Flk-1), and vWF
      that were special for blood vessel endothelial cells. RESULT: After 3D-cultured
      and induced with VEGF and bFGF in vitro in fibrin-gels and matrigel for 3-21
      days, BDMSC expressed CD34, CD31, Flt-1, Flk-1, and vWF came into vessel-like
      configuration. CONCLUSION: VEGF, bFGF as well as Flt-1 and Flk-1, expressed by
      BDMSC, may form a feasible microenviroment after induction and play an important
      role during processes of blood vessel endothelial cell differentiation and vessel
      like configuration forming of BDMSC. Mesenchymal stem cells may be applied to
      tissue engineering vascularization and injured tissue repairing by cell
      transplantation.

PMID- 16447634
TI  - [Preparation of xenogenic corneal stroma and its cytoconsistency].
AB  - OBJECTIVE: To explore the possibility that using the bovine corneal stroma to
      provide a suitable carrier on which the cells can grow for tissue engineering
      cornea. METHODS: Nine fresh bovine corneas were selected. Each cornea was cut
      into 2 pieces, and exposed to 0.25% trypsinase for various lengths of time (20
      minutes, 40 minutes, and 60 minutes) to get the stroma part with least cells and
      maintaining the collagen fibers arrangement. Samples obtained from each group
      were examined with scanning electron microscopy and HE staining. The left ones
      were freeze-dried and sterilized. The various concentrations of extraction were
      used to cultivate human fibroblasts, and a 3-(4,5-dimethylthiazol-2-yl)-2, (MTT)
      based colorimetric assay was taken to evaluate the exhistance of 5
      diphenyltetrazolium bromide cytotoxinic effects. Then the proper corneal stroma
      was used as a carrier to cultivated the rabbit corneal limbal cells which were
      planted on it in a concentration of 2 x 10(5)/cm2 in vitro. The cell-carrier
      samples were sent for scanning electron microscopy and HE staining. RESULTS: The
      corneal stroma had the least cells in the group acted with typsin for 60 minutes,
      while the collagen fibers arrangement was not so orderly as before. The
      extractions showed no significant difference in cell culture, and no obviously
      harmful effect on the cell growth. The rabbit corneal limbal cells presented a
      stratified growth on the bovine corneal stroma. CONCLUSION: The bovine corneal
      stroma without cells prepared using the typsin and lyophilization can be a
      suitable carrier for cell culture in vitro.

PMID- 16447635
TI  - [Treatment of rabbit corneal with skin epidermal stem cells].
AB  - OBJECTIVE: To construct artificial rabbit corneas with autologous skin epidermal
      stem cells and allogenic stromal cells in vitro and promote healing of corneal
      wounds. METHODS: Skin epidermal stem cells were isolated from autologous skin
      samples. Keratocytes were isolated from newborn cornea biopsies. The cells were
      combined with acellular porcine corneal stroma scaffold to construct artificial
      corneas. Then the constructed artificial corneas were used to repair severe
      vision loss caused by complete loss of corneal epithelial stem cells. RESULTS:
      Cultured skin epidermal stem cells and keratocytes were in good growth
      conditions. Cultured artificial corneas consisted of multiplayer epithelial cells
      growing on stroma equivalent consisting of stromal matrix with incorporated
      keratocytes. The in vitro constructed artificial corneas were histologically
      similar to normal rabbit corneas. Three months after transplantation, the cornea
      wounds were healed and the rabbit cornea became transparent. CONCLUSION: The
      artificial corneas were constructed successfully in vitro and can be used to
      repair severe vision loss caused by complete loss of corneal epithelial stem
      cells.

PMID- 16447636
TI  - [Potential of human adipose tissue derived adult stem cells differentiate into
      endothelial cells].
AB  - OBJECTIVE: To investigate whether human adipose derived adult stem (hADAS) cells
      can differentiate into endothelial cells. METHODS: Stem cells were isolated and
      expanded from adipose tissue and then induced to differentiate into cells of
      osteogenic, adipogenic and neurogenic lineages in vitro. hADAS cells were induced
      with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) to endothelial cells differentiation. hADAS cells were intravenously
      injected into mouse hindlimb ischemic models to test their ability to
      differentiate endothelial cells in vivo. RESULTS: hADAS cells were easily
      isolated and expanded in vitro. They had the ability to differentiate into
      osteogenic, adipogenic and neurogenic lineages. The cells expressed vascular
      endothelial growth factor receptor-2 (VEGFR-2, Flk1), and expressed endothelial
      markers when cultured with VEGF and bFGF. In response to local cues, hADAS cells
      in vivo differentiate into endothelial cells that contributed to neoangiogenesis
      in hindlimb ischemia models. CONCLUSIONS: Flk1+ hADAS cells have multipotential
      not only similar to bone marrow mesenchymal stem cells, but also exhibiting
      characteristics of endothelial progenitor cells. They may be a potential source
      of endothelial cells for cellular pro-angiogenic therapies.

PMID- 16447637
TI  - [Flow cytometry analysis and differentiation study of selected nestin positive
      cells].
AB  - OBJECTIVE: To verify the hypothesis that selected nestin positive cells derived
      from human fetal pancreas (according as medical ethnics) have surface markers
      similar to bone marrow mesenchymal stem cells (MSCs), and that these cells have
      multilineage potential. METHOD: The cell surface markers were determined by flow
      cytometry, and then the potential that these cells might be differentiated into
      adipocytes and osteoplasts were explored. RESULT: These cells have similar
      surface markers as MSCs of bone marrow origin. These cells was induced to
      differentiate into adipocytes and osteoplasts. CONCLUSION: Selected nestin
      positive cells derived from human fetal pancreas have certain characteristics of
      MSCs.

PMID- 16447638
TI  - [Repair of peripheral nerve gap with the use of tissue engineering scaffold
      complex].
AB  - OBJECTIVE: To study the feasibility to repair the peripheral nerve gap with
      tissue engineering scaffold complex that is composed of medical biodegradable
      material agarose hydrogel and nerve growth factor (NGF). METHODS: Chitosan tube
      containing agarose hydrogel and NGF was transplanted to bridge a 10 mm gap of
      injured sciatic nerve in rat. Chitosan duct without agarose hydrogel and NGF was
      used as negative control, while autograft nerve as positive control. Sixteen
      weeks after operation, the regeneration of nerve fiber was observed with
      morphological and immunohistochemistrical methods. RESULT: The number and
      diameter of regenerating nerve fibers bridged by the scaffold complex of agarose
      hydrogel and NGF were better than negative control group (P < 0.01) and reached
      the level of autograft nerve group. CONCLUSIONS: The new type of tissue
      engineering scaffold complex of agarose hydrogel and NGF may provide a
      microenvironment, as well as autograft nerve, to promote nerve regeneration. This
      technique may benefit patients with nerve injury in the future.

PMID- 16447639
TI  - [Transforming growth factor-beta1-loaded fibrin sealant promote bone marrow
      Mesenchymal stem cells to contract injectable tissue engineering cartilage in
      vivo].
AB  - OBJECTIVE: To investigate the feasibility that transforming growth factor-beta1
      (TGF-beta1) -loaded fibrin sealant (FS) promotes bone marrow mesenchymal stem
      cells (BMSCs) to create tissue engineering cartilage in vivo. METHODS: The BMSCs
      were isolated from healthy human and amplified in vitro, and then induced by
      defined medium containing TGF-beta1 and dexamethasone. After 7 days the induced
      BMSCs were collected and mixed with TGF-beta1-loaded FS or FS as BMSCs+ FS-TGF
      beta1 group and BMSCs+ FS experimental group. Then the mixture was injected by a
      needle into the dorsum of nude mice. In control group, only FS or BMSCs were
      injected. The tissue engineering specimens were harvested from nude mice 12 weeks
      later. Gross observation, average wet weight measurement, glycosaminoglycan (GAG)
      quantification, histology and immunohistochemistry were used to evaluate the
      results. RESULTS: The BMSCs have possessed the shape and functional characters of
      chondrocyte when transferred to a defined medium. After injection of the mixture,
      the cartilage-like tissue were formed in two experimental groups. Compared with
      BMSC+ FS group, the specimens of BMSCs +FS-TGF-beta1 group were larger and
      firmer. Alcian staining showed better metachromatic matrix formation. The GAG
      contents were significantly higher. Immunohistochemical staining of collagen type
      II was stronger. However, no cartilage-like tissue was formed in two control
      groups. CONCLUSION: TGF-beta1-loaded FS can promote BMSCs to contract injectable
      tissue engineering cartilage in vivo.

PMID- 16447640
TI  - [Autologus bone marrow-derived mesenchymal stem cells intracoronary delivery
      after acute myocardial infarction in miniature pig].
AB  - OBJECTIVE: To evaluate the possibility that using intracoronary delivery of
      autologus bone marrow-derived mesenchymal stem cells (MSCs) to improve the
      cardiac function after acute myocardial infarction (AMI) in miniature pig.
      METHODS: MSCs were cultured in Dulbecco's modified Eagle's medium-F12 (DMEM/F12)
      medium. AMI model was made by blocking the blood stream of the first diagonal
      branch in miniature pig, and released the branch after 90 minutes. After 10-14
      days, (4-6) x 10(7) culture-expanded autologus 4', 6-diamidino-2-phenylindole
      (DAPI)-labelled MSCs were transplanted into each host heart's AMI area through
      intracoronary way. Ultrasonic cardiography (UCG) was performed to observe the
      left ventricular function at 3 months after transplantation. The cellular
      transplanted hearts were harvested and investigated by immunohistochemical
      analysis. RESULTS: Left ventricular function of the MSCs group was improved
      significantly 3 months later compared with the control group [(54.65 +/- 3.39) vs
      (43.98 +/- 4.21)%, (P < 0.01)]. Exogenous MSCs survived and site-differentiated
      into cardiomyocytes in infracted hearts. CONCLUSION: MSCs can play a benificial
      role to repair damaged heart. Heart function can be improved after MSCs
      transplantation in porcine myocardial infarction model.

PMID- 16447641
TI  - [Association between genetic polymorphisms in methylentetrahydrofolate reductase
      and risk of lung cancer].
AB  - OBJECTIVE: To investigate the association between methylentetrahydrofolate
      reductase (MTHFR) polymorphisms and risk of lung cancer. METHODS: Totally 505
      cases with lung cancer and 500 frequency-matched controls were genotyped for the
      MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction
      fragment length polymorphism methods. The odds ratios (OR) and 95% confidence
      intervals (CI) were calculated using unconditional logistic regression model.
      Haplotype frequency was estimated using EH software. RESULTS: The frequency of
      the MTHFR C677T allele in cases was significantly higher than that in controls
      (53.5% vs 44.9%, P < 0.001). Compared with the 677CC genotype, the 677CT and
      677TT genotypes were associated with increased risk of lung cancer, with the OR
      being 1.43 (95% CI, 1.04-1.95) and 2.40 (95% CI, 1.61-3.59), respectively. In
      addition, a significant difference in the distribution of haplotype frequencies
      between cases and controls was observed. CONCLUSION: Functional polymorphism in
      MTHFR is associated with increased risk of lung cancer in Chinese population.

PMID- 16447642
TI  - [Application of modified TransFix-II technique in arthroscopic reconstruction of
      the anterior cruciate ligament using double tibial tunnel].
AB  - OBJECTIVE: To describe a modified TransFix- 11 technique for arthroscopic
      reconstruction of anterior cruciate ligament (ACL) using double tibial tunnel.
      METHODS: Twelve cases of ACL ruptures were reconstructed anatomically using
      modified TransFix- 11 technique. The double-looped semitendinosus and gracilis
      (DLSTG) tendon autograft was placed in a single femoral tunnel and double tibial
      tunnels to replace the anteromedial (AM) and posterolateral (PL) bundles of the
      original ACL. All the 12 patients underwent the same postoperative accelerated
      rehabilitation program. RESULTS: Lachman test, anterior drawer test and pivot
      shift sign, and mcmurray test showed negative results in all cases. All patients
      regained normal range of motion of the knee and gait 4-6 weeks after operation,
      and 8 patients returned to the low risk sports at 10-12 weeks. One year after
      operation, 9 patients were followed: the International Knee Document Committee
      (IKDC) analysis revealed normal or near normal knees in 9 patients. The Tegner
      score revealed that 6 patients regained their pre-injury activity level. No
      patient had a significant femoral or tibial tunnels enlargement, as shown by
      follow-up CT scan. CONCLUSION: Arthroscopic ACL reconstruction with double tibial
      tunnel using DLSTG and the technique of modified TransFix-II is reliable for
      replacement of the AM and PL bundles of the original ACL. The postoperative
      accelerated rehabilitation and the rapid restoration of the injured knee function
      can be expected.

PMID- 16447643
TI  - [Alteration of beta-amyloid and glutamate transporter in the brain of diabetes
      rats and the underlying mechanism].
AB  - OBJECTIVE: To investigate the alteration of beta-amyloid (Abeta) and glutamate
      transporter in the brain cortex of diabetes mellitus (DM) rats and the underlying
      mechanism. METHODS: The rats were randomly divided into control, DM, DM +NaCl,
      and DM +LiCl groups and diabetes was induced by streptozotocin. The activity of
      glycogen synthase kinase-3 (GSK-3) and the function of glutamate transporter were
      measured by 32P-labelling. The amount of Abeta was determined by enzyme-linked
      immunosorbentassay. RESULTS: In DM group, the level of Abeta40 increased (P <
      0.01), but the function of glutamate transporter was impaired (P < 0.05). The
      activity of GSK-3 was stimulated (P < 0.05). Compared with DM group, the level of
      Abeta40 was restored (P < 0.01), and the function of glutamate transporter was
      enhanced (P < 0.05) in LiCl treated group, accompanied by a decreased activity of
      GSK-3. CONCLUSION: Overproduction of Abeta and impaired glutamate transporter
      exist in DM rats, and increase of GSK-3 may play a crucial role in this process.

PMID- 16447644
TI  - [Hemodynamic responses to orotracheal intubation with fiberoptic bronchoscope and
      direct laryngoscope in children].
AB  - OBJECTIVE: To compare the hemodynamic responses to orotracheal intubation via
      fiberoptic bronchoscope (FOB) with conventional orotracheal intubation via direct
      laryngoscope (DLS) in children under general anesthesia. METHODS: Forty-three
      American Society of Anesthesiologist grade I-II children undergoing the elective
      plastic surgery and requiring orotracheal intubation were randomly allocated to
      either the DLS group (n = 20)or the FOB group (n = 23). After standard
      intravenous anesthetic induction, orotracheal intubation was performed using a
      DLS or a FOB. Noninvasive systolic blood pressure (SBP), diastolic blood pressure
      (DBP), heart rate (HR), and rate-pressure product (RPP) were recorded before and
      after anesthetic induction, at intubation, and 5 minutes after intubation with 1
      minute interval. RESULTS: In the DLS group, SBP, HR, and RPP at intubation
      increased significantly compared to their postinduction values (P < 0.05),but
      blood pressure, HR and RPP at intubation didn't differ from their preinduction
      values. The maximal values of SBP, HR and RPP during the observation (from the
      beginning of intravenous anesthetic induction to 5 minutes after intubation) were
      significantly higher than their preinduction values (P < 0.05). In the FOB group,
      blood pressure, HR and RPP at intubation increased significantly compared to
      their preinduction and postinduction values (P < 0.05), and the maximal values of
      blood pressure, HR and RPP during the observation were significantly higher than
      their preinduction values (P < 0.05). There were no significant differences in
      blood pressure and RPP at each time point during the observation between the two
      groups. The HR at intubation were significantly higher in the FOB group than in
      the DLS group (P < 0.05), but no significant difference was observed in the HR
      values at other time points during the observation between the two groups. There
      were also no significant differences in the maximal values of blood pressure, HR
      and RPP or the times to reach their maximal values between the two groups.
      CONCLUSION: General anesthesia of clinical standard depth can not effectively
      inhibit the pressor and tachycardiac responses caused by fiberoptic orotracheal
      intubation in children. As compared with DLS, FOB has no special advantages in
      preventing the cardiovascular stress responses to orotracheal intubation in
      children.

PMID- 16447645
TI  - [Chemical coupling of anti-dNA antibody on collagen coating].
AB  - OBJECTIVE: To evaluate the feasibility and stability of chemically conjugating
      IgM on collagen films. METHODS: IgM was labeled with 125I using the chloramine-T
      method. Six collagen films were randomly divided into two groups. In chemical
      coupling group 125I-labeled IgM was chemically coupled with the films through N
      succinmiclyl-3- (2-pyridyl-dithio) propionate reaction. In control group 125I
      labeled IgM was absorbed onto collagen films. The amount of IgM on the collagen
      films and the amount of IgM remained on the films after extensive rinsing with
      phosphate buffered saline were monitored by counting the radioactivity of 125I.
      RESULTS: The amount of antibodies loaded onto collagen films in the chemical
      coupling group was 15 times higher than that on the control films, showing
      significant statistical difference (P < 0.01). And the stability of conjugation
      antibodies on collagen films was significantly better than the control films.
      CONCLUSION: Chemical coupling is an effective approach to immobilize antibodies
      on collagen for further plasmid DNA tethering.

PMID- 16447646
TI  - [Compliance and efficacy of standard antenatal care model].
AB  - OBJECTIVE: To investigate the compliance of standard antenatal care (ANC) model
      with 12-13 visits currently used in Beijing region, and to assess the efficacy of
      this model in reducing adverse maternal and perinatal complication. METHODS: The
      clinical data of 544 women who delivered at Peking Union Medical College Hospital
      (West Section) from January 1, 1999 to December 31, 2002 were retrospectively
      reviewed and analyzed. Three areas were addressed in this paper: compliance of
      pregnant women with standard ANC model; association of maternal and perinatal
      complication with different number of ANC visits; effectiveness of screening for
      risk factors at the first ANC visit. RESULTS: A median of 8 ANC visits was made
      in 544 cases, of whom 22 cases (4.0%) never had ANC visit before delivery. The
      women were divided into three groups according to the status of residence and
      education levels: temporary residents in Beijing city (group A), permanent
      residents with middle or low education level (group B), and permanent residents
      with high education level (group C). The average number of ANC visits in group A
      was 4.55 +/- 3.1, which was much lower than in group B (8.71 +/- 2.2) and in
      group C (9.56 +/- 2.1) (P < 0.001). The mean duration of gestation at the first
      ANC visit in group A was (25.44 +/- 8.8) weeks much longer than (15.58 +/- 5.8)
      weeks in group B and (14.24 +/- 3.2) weeks in group C (P < 0.001). Among 544
      cases, 93 (17.1%) had ANC visit for 0-3 times, 299 (55.0%) for 4-9 times and 152
      (27.9%) for > or = 10 times. There was no statistical difference among varied
      number of ANC visits when the results were pooled for pregnancy induced
      hypertension, gestational diabetes mellitus, vaginal bleeding at the second and
      third trimesters, postpartum hemorrhage, fetal macrosomia, premature rupture of
      membrane, and fetal distress (P > 0.05). An increase in the number of ANC visits
      was associated with the decreased rates of fetal growth restriction (P < 0.05)
      and premature delivery (P < 0.05), whereas it was paralleled with increased rates
      of anemia and cesarean section (P < 0.001). It was found that 35.6% of women who
      developed maternal and perinatal complications would be identified through
      screening for risk factors at the first ANC visit. CONCLUSIONS: Standard ANC
      model is currently not well complied. It has limited efficacy in reducing most
      maternal and perinatal complications. A more practical and effective ANC model
      for low educated women and temporary residents needs to be explored.

PMID- 16447647
TI  - [Effect of Coeloglossum. viride var. bracteatum extract on oxidation injury in
      sub-acute senescent model mice].
AB  - OBJECTIVE: To study the anti-aging effects of Coeloglossum. viride (L) Hartm.
      var. bracteatum (Willd) Richter extract (CE) on senescent model mice induced by D
      galactose and sodium nitrite. METHODS: After one week of accommodation, 60 female
      NIH mice were divided into six groups with 10 mice in each group: normal control
      group, aging model group, Piracetam (positive control) group [300 mg/ (kg x d)],
      and CE reatment groups [2.5, 5, and 10 mg/ (kg x d)]. Mice in aging model group,
      Piracetam group, and CE treatment group were consecutively intraperitoneally
      injected with D-galactose [120 mg/ (kg x d)] and sodium nitrite [90 mg/ (kg x d)]
      for 60 days. From day 47, mice in Piracetam group and CE treatment group were po
      given Piracetam 300 mg/ (kg x d) or CE 2.5, 5, and 10 mg/ (kg x d). Mice in
      normal control group and aging model group were po given saline. The drug
      administration lasted for 14 days. Water maze test was performed to evaluate the
      learning and memory function in the mice. The activity of superoxide dismutase
      (SOD), the content of malondialdehyde (MDA), and the activities of
      adenosinetriphosphatase (ATPase), and monoamine-oxidase (MAO) in brain tissue
      were measured. RESULTS: The latencies in water maze test in aging model group
      mice were significantly longer than in normal control group (P < 0.01, P < 0.05),
      and the number of errors increased (P < 0.05). In aging model group mice, the
      activities of SOD, Na+K(+)-ATPase, and Ca2+Mg(2+)-ATPase decreased (P < 0.01, P <
      0.05), while the content of MDA and the activities of MAO-A and MAO-B increased
      (P < 0.01). Piracetam [300 mg/ (kg x d), po] and CE [2.5, 5, 10 mg/ (kg x d), po]
      ameliorated the above changes in aging model mice. CONCLUSION: CE may improve the
      memory dysfunction induced by consecutive injection of D-galactose and sodium
      nitrite,and has nootropic and antiaging effects.

PMID- 16447648
TI  - [Anterior corneal topographic changes after scleral buckling surgery].
AB  - OBJECTIVE: To investigate corneal refractive changes after scleral buckling
      surgery. METHODS: In a prospective self-controlled clinical study, we
      investigated the changes of refractive power, astigmatic power, astigmatic axis,
      and irregular astigmatic power of anterior corneal surface following scleral
      buckling surgery for retinal detachment in 30 patients (30 eyes). The corneal
      shapes were detected by Orbscan II topography at 1 day before surgery, and 1
      week, 1 month, and 3 months after surgery. The effects of some surgical factors
      on the anterior corneal refractive changes were analyzed. RESULTS: After surgery,
      refractive power on corneal anterior surface decreased significantly in
      peripheral zone at 1 week (P < 0.01). Astigmatic power increased obviously in
      central zone. The direction of astigmatic axis matched the direction of the
      buckle, and changed obviously in central zone after 1 week (P < 0.05). Irregular
      astigmatic power did not change significantly. There was a significant
      correlation between the encircling length/the buckle width and the refractive
      changes of corneal anterior surface. CONCLUSION: Refractive changes of corneal
      anterior surface following scleral buckling surgery was mainly temporary. Changes
      in the shape of corneal should be minimized to ensure a favorable postoperative
      visual acuity.

PMID- 16447649
TI  - [Effect of testosterone propionate on the distribution pattern of calcitonin gene
      related peptide in different motoneuron pools].
AB  - OBJECTIVE: To study the effect of testosterone propionate (TP) on the
      distribution pattern of calcitonin gene-related peptide (CGRP) in two types of
      motoneuron (Mn) pools in rats. METHOD: The double labeling of cholera toxin B
      subunit coupled with colloidal gold (CB-Au) retrograde identification combining
      with immunocytochemistry was mainly used to reveal the distribution pattern of
      CGRP-like immunoreactivity (CGRP-LI) and its changes in the motoneuron pools
      labeled by CB-Au. RESULT: TP injected intramuscularly 28 days later significantly
      decreased CGRP expression in Mn pool innervating extensor digitorum longus (EDL,
      fast-twitch), comparing with corresponding control and castration group
      respectively (P < 0.001), while no significant effect on Mn pools innervating
      soleus (SOL, slow-twitch, P > 0.05) was observed. CONCLUSION: EDL-Mn pool is more
      sensitive to testosterone propionate than SOL-Mn pool in regulating CGRP
      expression.

PMID- 16447650
TI  - [Lymphadenectomy in the treatment of malignant ovarian germ cell tumor].
AB  - OBJECTIVE: To evaluate the impact of lymphadenectomy on the relapse and survival
      of malignant ovarian germ cell tumor (OGCT). METHODS: The clinical data of 102
      OGCT cases treated in Peking Union Medical College Hospital from June 1980 to
      June 2003 were analyzed retrospectively. All the data about lymphadenectomy
      during primary and secondary surgery were collected, and other factors related to
      prognosis were also collected at the same time. Chi-squared test was applied in
      the univariate analysis related to relapse of disease. Cox model was applied in
      multivariate analysis related to relapse and survival of disease. RESULTS: Pelvic
      and paraaortic lymph node metastasis was not significantly related to prognosis
      in primary and secondary treated patients. Lymphadenectomy showed no significant
      impact on disease relapse and survival. In the primary treatment, International
      Federation of Gynecology and Obstetrics (FIGO) staging, chemotherapy regimen,
      residual tumor and lymphadenectomy were the significant factors related to the
      relapse. After being stratified for the chemotherapy regimen, lymphadenectomy was
      not significantly related to the relapse in bleomycin +etoposide +cisplatin or
      cisplatin +vincristine +bleomycin regimen group, and lymphadenectomy could
      prevent relapse in no chemotherapy or other chemotherapy regimen group. In
      relapsed patients, only residual tumor was significantly related to survival time
      after relapse. CONCLUSIONS: Pelvic lymph node metastasis is not the significant
      risk factor related to prognosis. Lymphadenectomy may have a beneficial effect on
      survival, although such effect is not significant. Although lymphadenectomy
      provides important information for prognosis, they provide little benefit to
      those patients already requiring chemotherapy based on the original operative
      findings. Lymphadenectomy should be performed to primary or relapsed patients by
      an expert surgical team.

PMID- 16447651
TI  - [Diagnosis and treatment of pancreatic serous cystadenoma].
AB  - OBJECTIVE: To summarize our experience on the diagnosis and treatment of
      pancreatic serous cystadenoma. METHOD: Data from 20 patients with pancreatic
      serous cystadenoma in Peking Union Medical College Hospital from 1994 to 2004
      were analyzed retrospectively. RESULTS: Ultrasound test was a good choice for
      primary diagnosis, while computed tomography scan and endoscopic retrograde
      cholangiopancreatography (ERCP) were better choice for the suspected cases. Most
      tumors (60%) were located in the body and tail of pancreas. The distal
      pancreatectomy was the commonest operation procedure. The main complications were
      pancreatic leakage (35%). The symptoms were resolved after surgical treatment.
      CONCLUSIONS: The treatment of pancreatic serous cystadenoma depends on the
      accurate diagnosis. Ultrasound and computed tomography are useful diagnostic
      methods. Surgical operation is the treatment of choice. Long-term follow-up has
      shown satisfactory outcomes if the tumors are resected completely.

PMID- 16447652
TI  - [Repairment of the large wound of endometriosis in the abdominal wall].
AB  - OBJECTIVE: To explore the plastic surgical repairment of the large wound of
      endometriosis in the abdominal wall. METHOD: Since March 2003 to December 2004, 6
      patients were treated with abdominoplasty and V-Y plasty for the wounds of the
      endometriosis in the abdominal wall. RESULTS: The endometriotic foci were removed
      thoroughly with pretty abdominal contour. No complications were observed.
      CONCLUSION: Abdominoplasty and V-Y plasty are good methods to repair the wounds
      of the endometriosis in the abdominal wall.

PMID- 16447653
TI  - [Effects of maternal hyperthyroidism and antithyroid drug therapy on thyroid
      function of newborn infants].
AB  - OBJECTIVE: To evaluate the relationship between the incidence of abnormal thyroid
      function of newborns and maternal hyperthyroidism with antithyroid drug therapy.
      METHOD: The clinical data of 35 neonates born to mothers with hyperthyroidism
      from 1983 to 2003 in Peking Union Medical College Hospital were retrospectively
      analyzed. According to the maternal thyroid function and the antithyroid drugs
      taken during pregnancy, subjects were divided into different groups. RESULTS: The
      proportion of abnormal thyroid function in newborn was 48.6% (17/35). The
      prevalences of primary hypothyroidism, subclinical hypothyroidism,
      hypothyroxinemia, and central hypothyroidism were 29.4%, 29.4%, 35.3%, and 5.9%,
      respectively. The incidence of abnormal thyroid function of neonates whose
      mothers did not take the antithyroid drugs (ATDs) until the third trimester of
      pregnancy was significantly higher than those without and with ATDs during the
      first or second trimester (P < 0.01). The incidence of abnormal thyroid function
      significantly increased in premature neonates, neonates whose mothers with modest
      or heavy pregnant hypertension, or neonates whose core serum thyroid-stimulating
      hormone or serum anti-thyroid peroxidase antibodies levels were abnormal.
      CONCLUSION: The risk of abnormal thyroid function of infants whose hyperthyroid
      mothers did not take ATDs until the third trimester of pregnancy may be
      increased. Prompt diagnosis and appropriate treatment of hyperthyroidism in
      pregnant women are essential for the prevention of neonatal thyroid functional
      abnormality.

PMID- 16447654
TI  - [Substrate specificity of three murine GDP-fucose: beta-galactoside alpha1,2
      fucosyltransferases].
AB  - OBJECTIVE: To compare the substrate specificity of three murine GDP fucose: beta
      galactoside alpha1,2-fucosyltransferases (alpha1,2-FT). METHODS: Three members of
      MFUT- I, -II and -III, coding for a alpha1,2-FT, a GDP-fucose, were cloned from a
      cDNA of murine small intestine by reverse transcription-polymerase chain
      reaction. The coding regions were ligated into mammalian expression vector pcDNA
      3.1 (pcDNA3.1-MFUT-I, pcDNA3.1-MFUT- II , and pcDNA3.1-MFUT- III) and were
      transiently transfected into COS-7 cells using a cellphect transfection kit. Then
      the cells were analyzed for expression and function of alpha1,2-FT and the
      substrate specificity of three alpha1,2-FT was compared. RESULTS: MFUT- I, -II,
      and -III exhibited sequence homology with human H (77%), Se (79%), and Sec1 (75%)
      genes, respectively. COS-7 cells transfected with pcDNA3.1-MFUT- I and pcDNA3.1
      MFUT- II showed alpha1,2-FT activity, but no activity was detected in COS-7 cells
      transfected with pcDNA3.1- MFUT-III. MFUT- II showed alpha1,2-FT activity with
      both asialo-monosialoteterahexosyl ganglioside (GA1) and monosialoteterahexosyl
      ganglioside (GM1) as substrates to produce fucosyl GA1(FGA1) and fucosyl
      GM1(FGM1), respectively, but MFUT- I only showed alpha1,2-FT activity with GA1.
      The relative activity of MFUT- II with GA1 was 80-90-folds higher compared with
      MFUT- I, and the relative activity of MFUT- II with GA1 was 10-20-folds higher
      than that of GM1. The fucosyltransferase encoded by the MFUT- II gene showed the
      enzyme activity not only responsible for the synthesis of type 4-H antigens FGA1
      and FGM1, but also responsible for the synthesis of type 1-H and 2-H antigens
      with lactotetraosylceramide and neolactotetraosylceramide as substrates.
      CONCLUSION: MFUT- II is the main alpha1,2-FT in mouse and MFUT- II can product
      type 4-H antigen FGA1 and FGM1, but MFUT- I only synthesizes FGA1. MFUT-III has
      no alpha1,2-FT activity.

PMID- 16447655
TI  - [Effects of tumor necrosis factor alpha on expression of phospholamban and
      intracellular calcium in cardiomyocytes].
AB  - OBJECTIVE: To explore the effects of tumor necrosis factor alpha (TNFalpha) on
      the expression of phospholamban (PLB) and sarco (endo) plasmic reticulum Ca(2+)
      ATPase (SERCA2a) and concentration of intracellular free calcium in
      myocardiocytes. METHODS: The neonatal rat myocardiocytes were randomly divided
      into 6 groups: treatment with different concentrations of TNFalpha
      (1,10,30,50,and 70 microg/L, respectively) and without TNFalpha (control). The
      mRNA and protein expression of PLB and SERCA2a were detected with one-step
      reverse transcription-polymerase chain reaction and Western blotting. The changes
      of intracellular free calcium concentration ([Ca2+]i) in cultured single neonatal
      rat cardiomyocyte were determined with Fluo-3/AM loading by laser scanning
      confocal microscopy. RESULTS TNFalpha significantly increased the expression of
      PLB mRNA and protein in a dose-dependent fashion. The ratio of PLB/beta-actin
      mRNA in myocardiocytes incubated with 10,30,50, and 70 microg/L TNFalpha
      significantly increased by 66%, 106%, 141%, and 189% compared with control (P <
      0.05), and protein levels significantly increased by 30%, 48%, 73%, and 114%
      respectively compared with control (P < 0.001), but there was no significant
      difference in PLB mRNA expression between the group treated with 1 microg/L
      TNFalpha and control group. TNFalpha had no effect on the expression of mRNA and
      protein of SERCA2a. TNFalpha (50 microg/L) incubated with cell for 24 hours
      diminished delta[Ca2+]i of single neonatal rat cardiomyocyte about 33% stimulated
      by isoproterenol (P < 0.01), but had no effect on delta [Ca2+]i of cardiomyocyte
      without isoproterenol stimulation. CONCLUSION: TNFalpha can increase the
      expression of PLB and decrease delta[Ca2+]i in cardiomyocytes, which may be
      related with its negative inotropic effects on cardiomyocytes.

PMID- 16447656
TI  - [Stem cells transplantation for ischemic heart disease].
AB  - At present, no effective therapeutic option for ischemic heart disease is
      available. The majority of the data on stem cell transplantation coming from
      preclinical animal studies and clinical research in small scale demonstrate that
      it may improve cardiac function. However, serious questions about its safety have
      yet to be answered.

PMID- 16447657
TI  - [Directed differentiation embryonic stem cells into the chondrocyte].
AB  - Cartilage is a tough, elastic, and fibrous connective tissue, composed of
      chondrocyte and extracellular matrix (ECM) structural entity. Because of the poor
      self-regeneration capabilities of chondrocytes, cell transplantation is
      necessanry once the cartilage is damaged. Traditionally autologous chondrocytes
      implantation is applied at the damage site, which has many problems such as the
      losing of its primary characteristics. A well-defined and efficient protocol to
      direct the differentiation of embryonic stem cells into the chondrocyte will
      provide a novel choice for cartilage repair. This article reviews some major
      progresses in this field.

PMID- 16447658
TI  - [Vascular differentiation of hematopoietic stem cells and possible application in
      the treatment of limb ischemic diseases].
AB  - Hematopoietic stem cell (HSC) is the first discovered and well studied tissue
      stem cell. HSC transplantation has been successfully applied to cure a variety of
      diseases of hematological and immunological systems. It has long believed that
      HSC and angioblast come from the common stem cell, the hemangioblast. Recently,
      HSC has been demonstrated to be able to differentiate into vascular endothelial
      cells. In animal in vivo models, HSC transplantation can promote angiogenesis and
      improve limb ischemia. Several pilot clinical studies have shown that
      transplantation of bone marrow and granulocyte colony stimulating factor
      mobilized peripheral blood HSC promoted vascular reconstitution in ischemic
      limbs. Umbilical cord blood has been an important source of HSC for clinical
      transplantation. Animal studies have demonstrated the efficiency of cord blood
      HSC transplantation in improving critical limb ischemia. These studies have
      provided evidences that HSC can be used for the treatment of vascular diseases.

PMID- 16447659
TI  - [Role of hysteroscopy in the diagnosis of endometrial carcinoma].
AB  - With the apparently increasing incidence of endometrial carcinoma, much
      importance has been attached to the early and exact diagnosis of endometrial
      carcinoma. This article mainly focuses on diagnostic techniques of endometrial
      carcinoma, especially diagnostic hysteroscopy and its assessment of myometrial
      invasion as well as stage of endometrial carcinoma. Whether hysteroscopy
      increases the risk of microscopic extrauterine spread is also discussed in this
      article.

PMID- 16447660
TI  - [Single nucleotide polymorphisms, inflammation and nutrition of genes].
AB  - Inflammation is part of the immune response, and inflammation may also induce or
      exaggerate some diseases through production of pro-inflammatory cytokines. More
      evidence have shown that the individual level of cytokine production is affected
      by single nucleotide polymorphisms in cytokine genes. Furthermore, as several
      nutrients participate in DNA protection and stabilization, altering gene
      expression and individual phenotype, nutrition has important interaction with
      inflammation. The purpose of this review is to give a recent update informations
      on the interaction of single nucleotide polymorphisms, inflammation and
      nutrition.

PMID- 16447661
TI  - The brain-resuscitation acupuncture method for treatment of post wind-stroke
      mental depression--a report of 45 cases.
AB  - In order to observe the therapeutic effects of the brain-resuscitation
      acupuncture method for post wind-stroke mental depression, 90 such cases were
      randomly divided into two groups, each consisting of 45 cases. For the treatment
      group, the brain-resuscitation acupuncture method was adopted, with Neiguan (PC
      6), Renzhong (GV 26), Sanyinjiao (SP 6), Baihui (GV 20), and Shenmen (HT 7)
      selected as the main points. For the control group, oral medication of Fluoxetine
      was prescribed. Therapeutic effects and changes in the HAMD integrals of the two
      groups were observed. The total effective rate in the treatment group was 77.7%,
      and that in the control group was 75.1%, showing no significant difference
      between the two groups (P>0.05). The average effect starting time of the
      treatment group was 11.58 +/- 4.89 days, while that of the control group was
      15.96 +/- 6.50 days, showing a significant difference between the two groups
      (P<0.05). It can be concluded that for the post wind-stroke mental depression,
      the brain-resuscitation acupuncture method may show a good and quicker
      therapeutic effect with no side effects as compared with pharmacotherapy.

PMID- 16447662
TI  - Evaluation on the therapeutic effects of digital acupoint pressure for obstetric
      spastic cerebral palsy.
AB  - To probe the evaluation methods for effects of TCM treatment of cerebral palsy
      through clinical observation on the digital acupoint pressure in treating
      obstetric spastic cerebral palsy. From 1998-2003, 40 cases of spastic cerebral
      palsy were treated with digital acupoint pressure therapy. Ten indexes including
      intelligence, language, salivation, hand-grasping, thumb-adduction, turnover,
      sitting, standing, walking, and scissors-gait were divided into the 4 grades of
      normal, mild abnormal, moderate abnormal, and severe abnormal (dysfunction),
      respectively marked as 6, 4, 2, and 0 point, with 2 points increased for
      improving each grade of each item after the treatment. Meanwhile, the ranges were
      recorded and evaluated before and after the treatment on shoulder-abduction,
      elbow-extension, wrist-extension, forearm-backward-rotation, hip-abduction,
      straight-leg-lifting, knee-extension, and ankle-dorsiflexion. Those with the
      improvement of 10 degrees, 15 degrees, 20 degrees, 25 degrees, and 30 degrees in
      the range of movement of their contractured joints would obtain respectively 1,
      2, 3, 4, and 5 points. There were significant differences before and after the
      treatment in the 18 items under observation except for intelligence, with obvious
      improvement shown after the treatment (P<0.01), the effective rate being 92.5%.
      The therapeutic criteria set in this research are well established in reflecting
      the functional improvements of the patient.

PMID- 16447663
TI  - Prof. Chen Quanxin's experience in acupuncture treatment.

PMID- 16447664
TI  - Effects of the lifting manipulation of scalp acupuncture for raising myodynamia
      of the affected limbs in hemiplegic patients due to cerebral thrombosis.
AB  - OBJECTIVE: To provide a new therapy with definite quality controllable
      therapeutic effects for functional restoration of the affected limbs in
      hemiplegic patients due to cerebral thrombosis. METHOD: 180 patients with
      hemiplegia due to cerebral thrombosis were randomly divided into 2 groups: the
      treatment group (treated with scalp acupuncture by using the lifting
      manipulation) and the control group (treated with scalp acupuncture by using the
      twirling manipulation). Evaluations were given for the two groups based on the
      improvement of myodynamia and comprehensive functions after the treatment.
      RESULTS: Both groups showed increased myodynamia, but with different cured and
      much relieved rates (86.67% in the treatment group and 5% in the control group,
      P<0.01). CONCLUSION: Scalp acupuncture with the lifting manipulation can
      dramatically increase myodynamia of the affected limbs in hemiplegic patients due
      to cerebral thrombosis.

PMID- 16447665
TI  - Acupuncture treatment for multiple aortitis--a clinical report of 40 cases.
AB  - In order to evaluate the therapeutic effects of acupuncture-moxibustion on
      multiple aortitis, 80 cases (with involvement of the main arteries in the head
      and arms) were randomly divided into a treatment group treated with acupuncture
      moxibustion, and a control group treated with TCM and western drugs. The
      therapeutic effects were compared. The total effective rate was 95% in the
      treatment group (including 15% of the cure rate and 62.6% of the marked relief
      rate), and the total effective rate was 75% in the control group (including 12.5%
      of the marked relief rate). There was a significant difference in the therapeutic
      effects (P<0.01) between the two groups. It can be concluded that acupuncture
      moxibustion is obviously superior to the routine drug therapy for treatment of
      multiple aortitis.

PMID- 16447666
TI  - Acupuncture treatment for 76 cases of ulcerative colitis.

PMID- 16447667
TI  - Examples of clinical application of moxibustion with moxa-sticks.

PMID- 16447668
TI  - Thirty-two cases of acne treated with blood-letting puncture, cupping and Chinese
      drug facemask.
AB  - To observe the therapeutic effect on acne treated with blood-letting puncture,
      cupping and Chinese-drug facemask. Thirty-two patients with acne were treated
      with above-mentioned therapeutic method. Cure, improvement and ineffectiveness
      were respectively found in 24, 7 and 1 case, with a curative rate of 75.0% and a
      total effective rate of 96.8%. The combination of blood-letting puncture, cupping
      and external application of Chinese-drug facemask is effective in treating acne.

PMID- 16447669
TI  - Needling Neiguan (P 6) for treatment of low pulse pressure syndrome--a report of
      31 cases.
AB  - OBJECTIVE: To observe the impact of needling Neiguan (P 6) on the cardiovascular
      functional status in low pulse pressure syndrome. METHOD: 49 eligible patients
      were randomly assigned to a acupuncture group with bilateral Neiguan (P 6)
      needled for successive 3 days, and a medication group given a daily 20 mL of
      Shenmai Injectio intravenously dripped for successive 6 days. The blood pressure,
      pulse pressure, stroke volume (SV), cardiac output(CO)/min, left ventricle work
      index (LVWI), mean arterial pressure (MAP), total peripheral resistance (TPR),
      coronary perfusion pressure (CPP), pulmonary arterial wedge pressure (PAWP),
      effective blood volume (BV), blood viscosity (N), microcirculation half renewal
      rate (MHR), and cardiac muscle blood volume (CMBV) were determined before and
      after the treatment, which were compared with the parameters obtained in 23
      healthy subjects. RESULTS: The decreased pulse pressure of all patients before
      treatment (P<0.01) increased significantly after treatment (P<0.001). The levels
      of SV, CO, LVWI, PAWP, BV, MHR and CMBV were lowed when compared with the healthy
      subjects before treatment (P<0.01), but all of them significantly increased after
      treatment (P<0.01). The increased CPP, TPR and N before treatment (P<0.01) were
      decreased after treatment (P<0.01). CONCLUSION: The therapeutic effect of
      acupuncture at point Neiguan (P 6) was better than medication though some of the
      indexes showed no significant difference (P<0.05).

PMID- 16447670
TI  - Fifty cases of child restless syndrome treated with the integrated method of
      Chinese herbal drugs and auricular-plaster therapy.

PMID- 16447671
TI  - Clinical observation on treatment of 2,062 cases of immune infertility with
      integration of traditional Chinese medicine and western medicine.
AB  - To study the therapeutic effect of integrated traditional Chinese medicine and
      western medicine on female immune infertility. 3,496 women suffering from primary
      or secondary infertility had their ASAb, EMAb, AOAb and ACAb level tested, with
      the positive rate of 23.11%, 34.95%, 20.77% and 30.41% respectively. 2,062
      positive cases were periodically treated with the Chinese drug Xiaokangwan plus
      dexamethasone, vitamin E and vitamin C for 2 periods as a course of treatment. At
      the end of a treatment course, the rate for the antibodies to turn negative
      reached over 85% and the average pregnant rate reached 36.66%. The treatment of
      immune infertility with the integrated approach can reduce or eliminate the
      influence of antibodies in the serum of patients on various links of pregnancy,
      thus reaching the goal of curing infertility.

PMID- 16447672
TI  - Dr. Chen Xiangjun's experience in using pair of drugs to treat rheumatic
      diseases.

PMID- 16447673
TI  - Gu sui bu (Rhizoma drynariae)--a good drug for senile dementia.

PMID- 16447674
TI  - Effect of liangxue huoxue xiaoyin tang on serum levels of TNF-alpha, IFN-gamma
      and IL-6 in psoriasis of blood-heat type.
AB  - To explore the effect of Liangxue Huoxue Xiaoyin Tang (LHXT Decoction of Removing
      Heat from the Blood and Promoting Blood Flow to Eliminate Psoriasis) on serum
      levels of tumor necrosis factor-alpha (TNF-alpha), interferon (IFN-gamma) and
      interleukin-6 (IL-6) in psoriasis of blood-heat type. Blood samples from both the
      treatment group (N=33) and control group (N=30) were taken before and after
      treatment, and the serum levels of TNF-alpha, IFN-gamma and IL-6 were determined
      by radio-immunoassay and ELISA. The total effective rate achieved in the
      treatment group was 90.91%. The remarkably high serum levels of TNF-alpha, IFN
      gamma and IL-6 in patients before treatment (P<0.01) were obviously decreased
      after one course of treatment (P<0.05) and were close to those of healthy
      subjects after two course of treatment (P>0.05). The data demonstrate that LHXT
      has the actions of reducing serum levels of TNF-alpha, IFN-gamma and IL-6 in
      psoriasis of blood-heat type, and may exert a pharmacological effect targeting at
      the cytokines.

PMID- 16447675
TI  - An experimental research into the anti-aging effects of Radix Arctii Lappae.
AB  - PURPOSE: To delve into the anti-aging effects and mechanism of Niubanggen (Radix
      Arctii Lappae). METHOD: The activity of SOD and the content of MDA and lipofuscin
      in the tissues of the liver, brain and blood serum of the lab rats were observed
      30 days after they had been fed with the Niubanggen decoction. RESULT: The
      activity of SOD in the liver tissue and blood serum of the decoction-fed lab rats
      was improved dramatically (P<0.05 or P<0.01), the content of MDA in the brain
      tissue and blood serum lowered obviously (P<0.05 or P<0.01), and the content of
      lipofuscin dropped distinctly (P<0.01). CONCLUSION: The mechanism of the anti
      aging effects of the Niubanggen is mainly obtained by raising the activity of SOD
      and reducing the contents of MDA and lipofuscin.

PMID- 16447676
TI  - Experimental study on gufusheng in treatment of steroid-induced ischemic necrosis
      of femoral head in rabbits.
AB  - OBJECTIVE: To explore the mechanisim of compound Gufusheng in treatment of
      steroid-induced ischemic necrosis of femoral head (SINFH). Thirty-two rabbits
      were randomly divided into a blank control group (n=12) and a model group (n=20).
      The rabbits of the model group were established by intramuscular injection of
      prednisone acetate (0.32mg/kg/d) for 8 weeks, and 2 rabbits in each group were
      killed at the 6th and the 8th week respectively to investigate whether the model
      was successfully prepared. Then remainder in the model group was again randomly
      divided into group A (Gufusheng group, n=8) and group B (model group, n=8), while
      the rest of rabbits in the blank group constituted group C (n=8). The rabbits in
      group A were given Gufusheng Decoction by intragastric perfusion, and the rabbits
      in group B and C were fed with normal saline. After treatment for 4 weeks, the
      serum insulin-like growth factor-1 (IGF-1) and tumor necrosis factor-alpha (TNF
      alpha) levels in the rabbits of the 3 groups were determined by radioimmunoassay
      (RIA). The serum TNF-alpha decreased significantly and the IGF-1 level increased
      significantly in the Gufusheng group as compared with the model group (both
      P<0.01). Compound Gufusheng can prevent SINFH and promote repair of the tissue of
      necrosis of femoral head possibly via decreasing the TNF-alpha and increasing IGF
      1 level.

PMID- 16447677
TI  - Advances of studies on mechanisms of drugs for activating blood circulation and
      removing blood stasis in treatment of primary liver cancer.

PMID- 16447678
TI  - Acupuncture treatment of obesity.

PMID- 16447679
TI  - [The role of clinical history in the evaluation of balance and spatial
      orientation disorders in the elderly].
AB  - Balance and spatial orientation complaints are very frequent in the elderly. The
      aetiology of these complaints may be related to specific peripheral or central
      vestibular disorders or to an extravestibular dizziness resulting from impairment
      or disease in multiple systems. A preliminary diagnostic orientation, permitting
      the patient to be referred to the most appropriate specialist (otologist,
      neurologist, consultant in internal medicine, psychiatrist, physical therapist)
      would be very useful. We examined 163 patients, referred for balance and spatial
      orientation complaints to the otoneurological outpatient services of 6 university
      hospital centres in the northern and central Italy, by a detailed questionnaire
      about characteristics, frequency, duration of any dizziness symptom and by a
      bedside vestibular examination. The questions were designed to determine whether
      the patients suffered from true vertigo, considered to be an expression of a
      vestibular disorder, or of an aspecific dizziness of multifactorial origin.
      Comparison of the conclusions of the vestibular examination and the diagnostic
      hypotheses deduced from the clinical history showed a high degree of concordance
      (Cohen Index 70.5%). To the patient, vertigo and dizziness are synonymous. By
      asking appropriate questions, a clearer picture should begin to emerge from the
      patient complaints so that distinction between psychogenic, nonvestibular and
      vestibular causes can be made. The importance of obtaining a good history cannot
      be overemphasized. A correct and rigorous approach by the general practitioner
      could be of great utility both for the health of the patient and for the
      efficiency of the national health service. The vestibular examination proved that
      about half the patients (80/163) suffered from vestibular disorders, mainly of
      peripheral origin (BPV, Meniere's disease, vestibular neuritis).

PMID- 16447680
TI  - [The relationship between cognitive impairment, anxiety-depression symptoms and
      balance and spatial orientation complaints in the elderly].
AB  - Balance and spatial orientation complaints, generically defined as "dizziness",
      are frequent in the elderly. They can cause a greater or lesser degree of
      handicap, and be associated with a greater or lesser degree of cognitive
      impairment and anxiety-depression symptoms. We examined 163 patients, referred
      for these complaints to the otoneurological outpatient services of 6 university
      hospital centres of the northern and central Italy, performing a bedside
      vestibular examination. The test allowed to distinguish between subjects with
      specific vestibular disorders (mainly BVP, Meniere's disease and vestibular
      neuritis) and subjects in who the vestibular examination was not significant, and
      whose dizziness probably resulted from impairment or disease in multiple systems.
      The evaluation of the degree of handicap, using the Dizziness Handicap Inventory,
      showed that in the former group the physical parameters were significantly
      impaired with respect of a group of 81 age matched healthy controls, whereas the
      functional and emotional parameters were not. The evaluation of the degree of
      anxiety-depression, using the Hospital Anxiety Depression Scale, showed that all
      elderly people with balance and spatial orientation complaints present a degree
      of anxiety, but not of depression, greater than the controls, irrespective of the
      vestibular or extravestibular origin of the symptoms. The evaluation of the
      cognitive level, using the Mini Mental Test, showed that it is similar to the
      cognitive level in the controls when, according to the results of the
      otoneurological examination, the balance and spatial orientation complaints are
      due to vestibular disorders, but it is impaired when these symptoms are related
      to a dizziness of multifactorial aetiology. The presence of comorbidities is also
      higher in these patients. It is likely that in the elderly balance and spatial
      orientation complaints not caused by specific vestibular disorders are due to a
      dizziness of multifactorial origin, both organic and psychic, that can be
      classified as a geriatric syndrome.

PMID- 16447681
TI  - [IgG heterophile antibody causes false positivity for CA19-9, which is overcome
      with bovine immunoglobulin].
AB  - Immunoassay using antibodies is widely applied to measure various clinical
      parameters such as tumor markers. However, many mechanisms of interference for
      this method have been reported. We studied serum sample showing false positive
      CA19-9 values in the range of 24 to approximately 286U/ml depending on the
      reagent lots used. PEG-pretreated serum did not show false positivity. Using high
      performance liquid chromatography (HPLC), the CA19-9 false positive peak was
      obtained around 160kD, which is the same as IgG. Antibody-coated microbeads,
      labeled antibody and buffer were used in different combinations between different
      lots, and the buffer was found to be the cause of false positive findings. The
      amount of bovine IgG contaminated in bovine serum albumin(BSA) in the reagent
      buffer markedly differed between lots of BSA, and reagent with a low amount of
      bovine IgG showed false positive results. Bovine immunoglobulin was superior to
      mouse IgG in the attempt to avoid a false positive reaction. We concluded that
      the cause of false positive CA19-9 findings in this serum sample was IgG
      heterophile antibody, which reacts with both of mouse and bovine IgG. The
      heterophile antibody had greater affinity to bovine IgG than to mouse IgG. The
      difference between CA19-9 values obtained by different reagent lots was due to
      different amounts of bovine IgG contaminated in BSA used in the reagent. Bovine
      immunoglobulin was superior to mouse IgG in the attempt to absorb the heterophile
      antibody and avoid false positive reaction in this case.

PMID- 16447682
TI  - [Analysis of proteins in urinary tract stones and urine of urolithic patients].
AB  - In order to investigate the mechanism of urinary tract stone formation, we
      analyzed protein components in urine and the stone. Urinary proteins of healthy
      subjects and urolithic patients as well as protein components urinary tract stone
      of the urolithic patients were analyzed by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE). Electrophoretic patterns of urinary proteins of
      the patients differed from those of healthy subjects after separating protein
      patterns into those larger than 66kDa or smaller than 30kDa. Protein constituents
      of urinary tract stone were mainly separated into 18 bands ranging from 26.8 to
      143 kDa. Major bands among these 18 bands differed among stones from different
      patients. On western blotting, the developed intensities of Tamm-Horsfall protein
      (THP) were fainter than those of healthy subjects. Whereas intensities of albumin
      (ALB) were stronger than those of healthy subjects. Moreover, blotting patterns
      of THP of the patients on non-reducing SDS-PAGE were obviously broad. Thus, we
      suggest that analysis of fractionated urinary proteins or protein components of
      urinary tract stone may provide a tool for monitoring the prognosis or relapse in
      the patients.

PMID- 16447683
TI  - [Present conditions and future prospects of the at-home examination system].
AB  - It became say the preventive times than a treatment now. We did "the remoteness
      examination" that it was at home possible for from 1986 while the making of
      consciousness to "follow one's health by oneself' was demanded. I begin colon
      cancer examination, and now an examination item menu extends to 58 kinds.
      Remoteness examination is inspection and a support system of the making of health
      to assume medical call center a nucleus of 24 hours. Such a system described the
      times setting which became necessary and gathered up a role of the at-home
      examination system which aimed at cancer and a lifestyle-related disease and
      early discovery and a review of a habit and significance, the future prospects
      about a problem.

PMID- 16447684
TI  - [Sampling and conveyance of mail testing].
AB  - In mail testing, a testee collects samples at home from his or her own body, and
      mails them to the medical institution. Because the testee does not need to attend
      the medical institution, an advantage of mail testing is that it is not time
      consuming. Because the amount of sample is small and time from sampling to
      measurement is long, the manner of collecting and transporting samples are
      important factors affecting the precision of the result. There is the risk that
      inappropriate sample picking can occur, as the testee, who is not skilled in
      medical testing, may obtain the sample. Moreover, the samples may include blood,
      urine, secretions, and so on. Depending on the purpose of the test, the transport
      and sampling method varies, and the character of the sampling device and
      transport method influence the procedure required. I describe collection methods
      and other issues in this paper according to medical examination item, sample, and
      sampling.

PMID- 16447685
TI  - [Current status for OTC examination (test)].
AB  - Upgrading and expanding of preventive measures for lifestyle-related diseases is
      an urgent national priority because they are recognized as the most important
      health risks by both the general population and government. With such a social
      background, the spread of self-medication by self-test is eagerly awaited by
      health-oriented individuals. In this paper, legal position of OTC test reagent,
      OTC test equipment and remote healthcare as current status of OTC test are
      explained, reference is made to the current status of their diffusion here in
      Japan, and some typical examples of "self-collection sample and corresponding OTC
      test item" are clearly described. In consideration of the large number of
      potential patients with folk disease such as metabolic syndrome, drug stores
      should be an accessible and convenient spot for Japanese people to enjoy the
      benefit of OTC test by obtaining test kits for such diseases.

PMID- 16447686
TI  - [Future outlook for OTC examination (test)].
AB  - As the primary prevention of disease has been emphasized, there may be a growing
      need for well-conditioned development and spread of OTC test equipment, OTC test
      reagent and remote healthcare. Some typical examples of "simple and rapid
      examination items, which can be done at home by established technology" are
      explained in this paper and may be required in the near future by the whole
      Japanese population with a view to the current status of OTC test and the coming
      relaxation of governmental regulation. The reasons why these examination items
      should be commercialized as Switch OTC and the epidemiological background are
      further discussed. In relation to metabolic syndrome derived from super spreader
      like visceral mature adipocyte: SSVMAC, visceral fat rate measurement by
      bioelectrical impedance technology, postprandial blood glucose
      determination/urinary glucose determination, and urinary microalbumin detection,
      are explained with an example, together with the importance of early morning
      blood pressure recording. In the field of cancer and infectious diseases,
      immunological fecal occult blood determination as a marker of distal colorectal
      cancer, in which both higher survival rate and recovery rate by early detection
      have been established, Helicobacter pylori IgG antibodies or antigen examination
      including an examination of gastroduodenal disorder, prostate-specific antigen
      (PSA) and genital chlamydia are emphasized.

PMID- 16447687
TI  - [From the perspective of a clinical laboratory physician].
AB  - In Japan, self-monitoring of specific physical conditions is needed, and clinical
      laboratory testings have been increasingly performed outside of the hospital
      without the control and/or the supervision of medical doctors. Various items have
      been measured, which include not only body fat but biochemical markers, cellular
      analyses for malignancies, sexually transmitted bacterium and so on. Qualitative
      urinalyses for glucose and protein and for pregnancy, the reagents for which are
      purchased from pharmacy stores, have been estimated by the examinees themselves.
      Specimens for most other items described above are collected by examinees
      themselves, transported via mail or other media and measured in the commercial
      clinical laboratories. Quality assurance of sampling, transportation and
      measurement is essential. Therefore, a check-system not only by the owner or
      manager of the laboratories but also by the non-laboratory staff specialist is
      needed. Appropriate and exact informations regarding the results must be given to
      the examinees in consideration of their responsibility concerning the total
      processes, from preanalytical and analytical to postanalytical processes, of the
      measurement. Laboratory physicians and technologists should pay more attention to
      laboratory tests being performed by examinees and outpatients themselves, and
      participate more in improving and evaluating the usefulness of these tests.

PMID- 16447688
TI  - [Considering what clinical laboratories should become in the future--POCT, mail
      testing and OTC test].
AB  - Medical staff working in laboratories have shown little or no interest in POCT,
      mail testing and OTC test. POCT and mail testing are laboratory systems that
      respectively involve a series of laboratory processes (advice on sampling,
      interpretation of data, referral to a doctor, etc.). However, the usefulness of
      data in the two systems differs. Data in POCT are directly used for medical
      treatment and those in mail testing are used as screening for health control or
      self-medication. OTC test is different from POCT and mail testing. People buy
      materials for OTC test at a drug store, then perform it and interpret the data by
      themselves. There are several factors in the development of POCT, mail testing
      and OTC test, for example the awareness of people about participation and
      responsibility for their own medical care, control of lifestyle-related diseases,
      relaxation of governmental regulation and development of technologies. These
      laboratories will grow gradually and influence clinical laboratories in medical
      facilities as well as commercial laboratories. Medical technologists and
      laboratory physicians should contribute to the sound development of these
      laboratories. As things are being changing so rapidly, medical technologists and
      laboratory physicians are forced to realign.

PMID- 16447689
TI  - [My Kumamoto life of 19 years].
AB  - In this paper titled "My Kumamoto Life of 19 Years; The Travel for Times", the
      memorial lecture on my retirement from Kumamoto National University Corporation
      Integrated Medical and Pharmaceutical Sciences, Department of Biomedical
      Informatics (Chairman) is summarized. As they say "Time flies", time extends from
      seconds to years. The lecture includes a summary of my short term research and
      long term studies, such as age-dependant and gene-related changes in ageing over
      5 or more years in the healthy elderly. Short-term study mostly involved of newly
      evaluated assay methods for important substances such as the second level in the
      cell life span in the variation of lipid metabolite of cardiovascular diseases
      based on atherosclerosis, Alzheimer disease, and their evaluation by homogeneous
      assay of HDL-C, LDL-C, enzymatic assay for choline relating metabolites, and
      lipoperoxide as the results of free radical reactions. The intermediate-term
      studies were mainly on the development of total laboratory automation (TLA) for
      the management of the laboratory of the university hospital. The hospital has
      various degrees of sophistication in its laboratory services. Technicians were
      allowed to transport specimens immediately by using an air-shooter system after
      drawing blood, from the emergency room to the central laboratory. Routine
      specimens could be measured within 30 min and the results could be automatically
      sent to the physician's office. It greatly minimized reporting errors, decreased
      the exposure to biohazards, reduced labor expense, improved operation efficiency,
      and shortened turnaround time. Moreover, for the outpatients and emergency
      laboratories, we constructed a robotic measuring system which was assembled into
      a sequential method for the analysis of chemistry, hematology and urinalysis
      specimens by using a polyarticular robot. The robot arm extends to a bar-coded
      tube, picking up and placing test tubes on a turn table of autoanalyzers for
      analysis without manpower. This is the first known effective unmanned procedure
      for assay in the world of laboratory medicine. Also, our research on pathological
      informatics was begun. Our laboratory had 7 themes; the study of the reference
      intervals in the elderly as one of strategy of standardization on laboratory data
      (Drs. Uji Y, Sugiuchi H), the study of the activation mechanism of ribosomal
      proteins by the functions of blood cells (Drs. Shibuya Y, Senba U), the
      evaluation of diagnostic methods in latent ailments by gene analysis (Dr. Ando
      Y), the evaluation of a highly sensitive method for disseminated intravascular
      coagulopathy (Okajima K), the study of the neogenesis of blood vessels by
      physical invasion (Uchiba M), the study of the deposition mechanism of amyloid
      proteins and evaluation of the diagnostic methods in the autonomic system(Drs.
      Ando Y, Nakamura M), and the study of the function of blood stem cells in blood
      transfusion services (Drs. Yamaguchi K, Yonemura M, Tsunemi M). Finally, my long
      term work also included research into the early diagnosis and prediction of
      latent ailments and the variation of serum proteins levels in the healthy aged.
      The conclusion was that the reference value of healthy populations and
      individuals (intra-personal) who had no combined ailments, in follow-up for 5
      years, categorized by age, sex, and social conditions, gave a narrower range of
      variation than did large mixed populations (inter-personal), in laboratory tests
      and activity of daily living (ADL). Concerning the early diagnosis and prediction
      studies for the latent ailments in the aged, variations of serum protein levels
      in the healthy aged were classified into 3 types: serum proteins levels increased
      with advancing age (alphaAT, mainly acute phase reactant proteins), those that
      decreased with advancing age (albumin mainly transporting proteins) and proteins
      with no significant variation. The higher increase of the alpha1AT/beta2 III
      ratio in the healthy aged over 60 years old is suspected to create symptoms in
      the near future. The papers presented concerning ageing studies were presented at
      the APCCC Symposium (India, 2002) and the IFCC Symposium (Kyoto, 2002), and the
      TLA study was also presented at the Symposium of XX World Congress of Pathology
      and Laboratory Medicine (San Paulo Brazil 1999).

PMID- 16447690
TI  - [Anger expressive behaviors and its inhibitory factors in Japanese junior high
      school students: from the aspect to narcissism and norms].
AB  - This study investigated inhibitory factors in anger expressive behaviors among
      Japanese junior high school students. It also examined the relations between
      anger experiences and personality traits: verbal expression and narcissism. The
      result indicated that the factors of "friend relationships" and "cost-reward
      consciousness" were selected as those which inhibited anger expressive behaviors.
      Results of a covariance structure analysis were as follows. First, narcissistic
      personality elicited feelings of anger and depression and cognitions of inflating
      and calming, which all facilitated aggressive behavior, social sharing, and
      object-displacement as anger expressive behaviors. Second, verbal expression
      elicited cognitions of objectifying and self-reproaching, and the former
      inhibited anger expressive behaviors, though the latter facilitated them.
      Finally, "cost-reward consciousness" inhibited anger expressive behaviors for
      boys, while "normative consciousness" inhibited them for girls.

PMID- 16447691
TI  - [Influences of premenstrual syndrome on daily psychological states and salivary
      cortisol level].
AB  - The purpose of this study is to investigate the influences of premenstrual
      syndrome (PMS) on daily psychological states and salivary cortisol level. First,
      42 women recorded their PMS symptoms and basal body temperatures every day for
      approximately two menstrual cycles. Based on these prospective records of PMS
      symptoms, participants were divided into two groups: Normal group (n=22) and PMS
      group (n=17). There were no significant differences between the two groups in
      age, height, weight, age at menarche, menstrual cycle length, menstrual period,
      depression score, and stressor score. Next, 14 women (7 Normal group, 7 PMS
      group) were selected and they were measured twice, once during the premenstrual
      phase and once during the postmenstrual phase of their cycles. Each day, they
      took saliva samples and recorded their psychological states six times (from
      waking to going to bed) per day at their homes. Results showed that the fear
      score in PMS group was high in the premenstrual phase, whereas salivary cortisol
      level in PMS group was low in the same phase compared to the Normal group. These
      results suggested the possibility of dysregulation of the stress system in women
      with PMS.

PMID- 16447692
TI  - [The emergence of indirect reciprocity: evolutionary foundation of altruistic
      behavior based on "strict discriminator"].
AB  - Although there have been a number of studies that theoretically and empirically
      examined altruism based on direct reciprocity, few have been conducted on how
      altruism based on indirect reciprocity emerges. Recent advances in biological
      research, however, have suggested possible answers to the question. For instance,
      Nowak and Sigmund (1998a, b) proposed that what they called image scoring
      strategy made indirect reciprocity possible. After critically examining their
      work, Leimar and Hammerstein (2001) pointed out several limitations to the
      theory, and instead proposed standing strategy as an explanation. Although
      careful attempts to replicate the findings by them and Panchanathan and Boyd
      (2003) supported the arguments against image scoring, we reveal that standing
      strategy was not a satisfactory answer either. Based on a series of evolutionary
      simulations, we propose a new strategy, which we call strict discriminator, as an
      alternative. Strict discriminators are discriminating altruists, similar to the
      altruists with image scoring or standing strategy, but they are different in that
      its criterion for discrimination is stricter: unconditional altruists are
      excluded from their reciprocity.

PMID- 16447693
TI  - [Why is the diverse U letter relationship between embarrassment and psychological
      distance observed? In view of Schlenker and Leary (1982)'s self-presentation
      model of social anxiety].
AB  - The aim of the present study is to explain why there is "the diverse U letter
      relationship" between embarrassment and psychological distance empirically, in
      view of Schlenker and Leary (1982)'s self-presentation model of social anxiety.
      In Study 1, those relationships were observed in three different situations. In
      Study 2, the main effect of motivation for avoiding rejection and the damage of
      self-image, and their interaction with embarrassment was examined by hierarchical
      regression analysis. In the first step, the psychological distance, in the second
      step, the main effect of both, and in the third step, the interaction was
      entered. As a result, in the second step, both main effects were significant, but
      in the third step, only interaction was significant, and both main effects were
      not significant. This showed that the interaction could predict embarrassment,
      although the psychological distance was controlled. Finally, this result was
      discussed in view of social norm.

PMID- 16447694
TI  - [The relationship among four work commitment constructs of male college-graduate
      white-colors].
AB  - This study examined the causal links among job involvement (JI), career
      commitment (CC), affective commitment to the organization (ACO), and continuance
      commitment to the organization (CCO) under Japanese management practices. It was
      hypothesized that, JI influences CC, ACO and CCO directly, and influences ACO and
      CCO indirectly through CC. Survey data of 1470 male college-graduate white-colors
      were analyzed and results of path analysis (AMOS 4.0) showed a good fit with the
      model. As predicted, a positive relationship between CC and CCO was found for
      employees who had worked continuously for a large organization after graduation,
      but not for those who had turnover experiences. Theoretical and practical
      implications were discussed.

PMID- 16447695
TI  - [Development of the Japanese version of the Values In Action Inventory of
      Strengths (VIA-IS)].
AB  - Purpose of this study was to develop the Japanese version of the Values In Action
      Inventory of Strengths (VIA-IS). Japanese VIA-IS was back-translated, and their
      items were checked by the developers of the original VIA-IS. Participants in our
      standardization study were 778 undergraduate students who answered a battery of
      self-report questionnaires. The battery consisted of the Japanese versions of VIA
      IS, Subjective Happiness Scale, General Health Questionnaire, and NEO Five Factor
      Inventory (NEO-FFI). It was found that VIA-IS has high internal consistency and
      test-retest reliability. Happier people showed higher overall scores on VIA-IS
      and on almost all subscales both in men and women. Scores on VIA-IS were higher
      in the healthier group than in the unhealthy group, especially on the subscales
      of depression and impediment of social activities. Subscales of NEO-FFI were
      related to subscales of VIA-IS in a consistent way. High nomination groups showed
      significantly higher scores on eight subscales of VIA-IS than low nomination
      groups.

PMID- 16447696
TI  - [Prepulse inhibition among four strains of mice: effects of type of prepulse and
      lead time].
AB  - The effects of the type of prepulse (PP: visual 30 ms and auditory 30 ms) and
      lead time (50, 100, 200 ms) on the acoustic startle inhibition (prepulse
      inhibition: PPI) were tested and compared among four strains of inbred mice
      (BALB/cA, C3H/HeJ, C57BL/6J, and DBA/2N: all n=11). Following 40 trials of
      habituation using single pulse (white noise: P; 115 dB, 50 ms), the prepulse
      session made of 36 trials was conducted. In the habituation, the startle
      amplitude and peak latency were measured. DBA mice showed weaker startle
      amplitude than the other 3 strains. The peak latency of the BALB mice was faster
      than the other strains. The PPI by auditory PP was largest in C57BL, followed by
      C3H, and the least in BALB mice. DBA mice showed no PPI effect. The PPI under
      visual prepulse condition was observed only in BALB strain. Contrary, DBA mice
      showed prepulse facilitation in the 50 ms lead time condition.

PMID- 16447697
TI  - [Social skill deficits and depression in junior high school girls].
AB  - The purpose of the present study was to clarify the effect that social skill
      deficits had on depression in junior high school girls. Social skills and
      symptoms of depression were measured in a survey of 775 junior high school girls.
      About six weeks later, symptoms of depression were measured again, along with
      occurrence of stressors during the interval. It was found that social skill
      deficits were significantly associated with depression. A hierarchical regression
      analysis indicated that after partialling out the influence of first depression
      scores, social skill scores contributed significantly to the prediction of post
      interval depression scores. In addition, we found an interaction effect of social
      skill and stressor scores on post-interval depression, and girls with social
      skill deficits became more depressed when they experienced stressors.

PMID- 16447699
TI  - [Comprehension of emotions accompanied by everyday actions: comparison of
      biological-motion pictures with real-person pictures].
AB  - Forty participants viewed and interpreted videotapes that were composed of
      displays representing different human actions (e.g., running and washing hands)
      and emotions (pleasant, neutral, and unpleasant). Half the videotapes were usual
      movies of real persons and the other videotapes were biological motions as
      produced by 22 light points on a human body in otherwise total darkness. In each
      display, an expert or a novice played a series of large or small body actions
      under each emotion. We found that (1) pleasant-unpleasant feeling was well
      discriminated in the real-person displays and in the biological motion display of
      large body actions, but it was less discriminated in the biological-motion
      displays of small body actions, (2) actions by experts were rated to be pleasant,
      and (3) actions were successfully identified for the real displays of large
      actions by experts, but they were poorly identified for the biological-motion
      displays of small body actions by novices. These results suggested that the
      observers correctly judged the emotion of players that was represented through
      suitable actions.

PMID- 16447698
TI  - [Ways of finding meaning in negative experience and hesitation in self
      disclosure].
AB  - Narrative approach suggests that finding or creating meaning in one's own
      negative experience is important, and one of psychotherapeutic goals may be
      making it possible for the person to tell his/her in experience to others in a
      more positive way than otherwise. On the other hand, recent studies of self
      disclosure have suggested that disclosure of negative experience could be harmful
      to well-being or interpersonal relationship of the person. This study
      investigated the relationship between ways of finding meaning in negative
      experiences and hesitation in self-disclosure. A questionnaire about negative
      life experience was administered to 210 undergraduates. Results indicated that
      there were four different ways of finding meaning in negative experiences, and
      four factors of the hesitation could be classified into those having
      interpersonal and intra-personal negative implications. Believing that a negative
      experience had negative effects on life led to stronger hesitation in self
      disclosure. Interpreting a negative experience positively led to less intra
      personal hesitation. And holding no hope or optimistic perspective about a
      negative experience led to stronger interpersonal hesitation in self-disclosure.

PMID- 16447700
TI  - [Inflammatory and immune responses in arterial thrombus formation].

PMID- 16447701
TI  - [Acquired hemophilia: current status in Japan and immuno-biochemical features of
      autoantibodies to factor VIII].

PMID- 16447702
TI  - [Immune mechanisms and novel therapeutic targets for ITP].

PMID- 16447703
TI  - [Epitope analysis of anti-GPIIb-IIIa autoantibodies in chronic ITP].

PMID- 16447704
TI  - [Childhood acute leukemia: current status and future perspectives in MRD-based
      therapy].

PMID- 16447705
TI  - [Effect of glucocorticoids on bone mineral density in patients with idiopathic
      thrombocytopenic purpura].
AB  - To elucidate the effects of glucocorticoid on bone mineral density in idiopathic
      thrombocytopenic purpura (ITP) patients, we retrospectively evaluated the
      relationship between bone mineral density (BMD) and the total dose of
      glucocorticoid or the mean daily dose given. We found decreased BMD in 66.7% of
      the patients with ITP to whom glucocorticoid was given, though rather normal bone
      BMD was observed in 28.6% of ITP patients treated without steroids. The mean
      level of BMD was markedly decreased in steroid-treated patients compared with
      steroid non-treated patients (p < 0.01). The relationship between BMD and the
      total dose of glucocorticoid (p = 0.023) or the mean daily dose revealed a
      negative correlation (p = 0.022). This study showed that glucocorticoid-induced
      osteoporosis was observed in patients with ITP, similar to other diseases already
      reported. When we think of this disease, many cases tend to be followed for a
      long time, and as the majority of ITP patients is female, we should pay
      particular attention in the prevention of glucocorticoid-induced osteoporosis.

PMID- 16447706
TI  - [Angioimmunoblastic T-cell lymphoma complicated with EBV-associated B-cell
      lymphoma].
AB  - A 71-year-old man with high fever and enlargement of the bilateral submandibular,
      cervical and inguinal lymph nodes was hospitalized at Hiroshima University
      Hospital. The immunohistochemical and pathologic findings from the biopsy
      specimens led to the diagnosis of angioimmunoblastic T-cell lymphoma (AILT) with
      a cluster of CD20-positive cells. Flow cytometry analysis by two-color staining
      did not reveal any neoplastic B cells. Southern blot analysis showed
      rearrangement of both the IgH gene and the TCR gene. Furthermore, PCR of the IgH
      gene using DNA extracted from purified CD19-positive cells from the lymph nodes
      showed a monoclonal band, and it was different from that of purified CD138
      positive cells from the bone marrow. Furthermore, monoclonal Epstein-Barr virus
      (EBV) infection was detected with PCR using the SL18 and SL19 primers of the LMP
      1 gene. Numerous EBER-positive cells were detected diffusely in the lymph nodes.
      These findings indicated a diagnosis of angioimmunoblastic T-cell lymphoma
      complicated with EBV-associated B-cell lymphoma, and that immunodeficiency in
      AILT led to an expansion of EBV infected B-cells.

PMID- 16447707
TI  - [Acute lymphoblastic leukemia (L3) with t(2;3)(p12;q27), t(14;18)(q32;q21), and
      t(8;22)(q24;q11)].
AB  - A 50-year-old woman developed a subcutaneous tumor in the left lower leg. A
      biopsy led to the diagnosis of lymphoid malignancy. The malignant cells showed a
      B-cell immunophenotype. Karyotyping of the cells revealed t(14;18) and t(2;3).
      The patient was treated with chemotherapy, resulting in a transient response.
      Subsequently, tumor regrowth and bone marrow recurrence developed. Karyotyping of
      the bone marrow at relapse revealed a t(8;22) in addition to t(14;18) and t(2;3),
      which led to a diagnosis of acute lymphoblastic leukemia (ALL)-L3 (FAB). Although
      the patient was treated with several chemotherapy regimens, the disease was
      refractory to all the treatments. Fluorescence in situ hybridization (FISH) and
      the nested polymerase chain reaction (PCR) technique demonstrated rearrangements
      of the c-myc, bcl-2, and bcl-6 genes. ALL-L3 associated with t(14;18) is known to
      be complicated frequently with cerebrospinal infiltration and extramedullary
      lesions, and has a poor prognosis. In our case, the presence of the additional
      t(2;3) may have enhanced this patient's refractoriness to the treatment.

PMID- 16447708
TI  - [Spontaneous omental bleeding presenting as acute abdomen during treatment for
      polycythemia vera].
AB  - A 54-year-old woman with polycythemia vera (PV) presented as an emergency patient
      with acute abdomen. Her platelet count was 119 x 10(4)/microl. Computed
      tomography scan revealed fluid accumulation in the omentum and peritoneal space.
      An emergency laparotomy was undertaken because of severe abdominal pain and
      omental bleeding was diagnosed. Peritoneal hemorrhage and hematoma weighing in
      total 1040 g was drained. Although a part of the omentum and stomach was excised,
      we could not find any orifice from which bleeding could have occurred despite a
      thorough pathological examination. Massive hemorrhage should be considered in
      cases with PV presenting as acute abdomen, especially when the platelet count is
      extremely high (over 100 x 10(4)/microl).

PMID- 16447709
TI  - [Pulmonary MALT lymphoma with macroglobulinemia].
AB  - An 84-year-old man was diagnosed as having pulmonary MALT lymphoma in January
      1997. Six years later, he was admitted to our hospital with coughing and dyspnea
      in November 2003. Dissemination of MALT lymphoma was confirmed by findings of
      pleural effusion and bone marrow aspiration. A FISH analysis of cells from the
      pleural effusion revealed t(11;18)(q21;q21) and the serum level of IgM was 8,600
      mg/dl (M-protein). The diagnosis of secondary macroglobulinemia was made. The
      patient received rituximab monotherapy because he was very elderly. Pleural
      effusion has not been seen after the administration of rituximab, although there
      have been no changes in the lung mass and serum values of M-protein.

PMID- 16447710
TI  - [Phyllotypic progenitor and stem cell].

PMID- 16447711
TI  - [Diversity of hematopoietic stem cells].

PMID- 16447712
TI  - [Targeting Ras related proteins for leukemia therapy].

PMID- 16447714
TI  - [Molecular targeting therapy by anti-VLA-4 monoclonal antibodies for AML].

PMID- 16447713
TI  - [Possibility of targeting FLT3 kinase for the treatment of leukemia].

PMID- 16447715
TI  - [All-trans retinoic acid-induced erythema nodosum in acute promyelocytic
      leukemia].
AB  - A 24-year-old woman with acute promyelocytic leukemia was treated with all-trans
      retinoic acid (ATRA) as a remission induction therapy. After pneumonia in the
      neutropenic period was successfully treated with antibiotic treatment, there was
      recurrence of high fever alone, followed by the appearance of erythema nodosum
      with pain in her upper limbs on day 25 of ATRA therapy. Skin biopsy neither
      revealed infiltration of leukemic cells nor suggested Sweet's syndrome. We
      considered the eruptions to be associated with ATRA, and prednisolone (30 mg/day
      for 5 days) was administered. Although the administration of ATRA was continued
      until complete remission of the leukemia, the erythema nodosum rapidly
      disappeared following short-term steroid therapy and no recurrence was observed.
      ATRA-induced erythema nodosum is rare, however it should be recognized as a
      possible adverse effect in ATRA therapy.

PMID- 16447716
TI  - [Adams-Stokes attack due to complete atrioventricular block in a patient with
      acute promyelocytic leukemia during remission induction therapy using all-trans
      retinoic acid].
AB  - We describe a case of Adams-Stokes syncope due to complete atrioventricular block
      which occurred in a leukemic patient receiving all-trans retinoic acid (ATRA).
      Remission induction therapy was performed for a 46-year-old Japanese man with
      acute promyelocytic leukemia using ATRA (45 mg/m2), enocitabine (170 mg/m2, 5
      days), and mitoxantrone (4 mg/m2, 3 days). On the 25th day of chemotherapy,
      syncope suddenly occurred. Electrocardiography revealed a complete
      atrioventricular block, and a temporary pacemaker was inserted on the following
      day. The block was persistent and the cardiac rhythm was dependent on the
      pacemaker. ATRA was discontinued on the 29th day because the arrhythmia was
      believed to be an adverse reaction to the ATRA regimen. The normal sinus rhythm
      was restored 15 days thereafter, and the patient eventually reached remission. He
      subsequently received 4 courses of consolidation therapy without any
      cardiovascular complications. Although ATRA sometimes induces arrhythmias, to the
      best of our knowledge this is the first report in the literature of such a
      critical ATRA-related arrhythmia.

PMID- 16447717
TI  - [Angioimmunoblastic T-cell lymphoma accompanied by pure red cell aplasia].
AB  - A 71-year-old woman was admitted in December 2002 because of lymphadenopathy,
      hepatosplenomegaly and pleural effusion. She had severe anemia with hemoglobin
      5.9 g/dl and a reticulocyte count of 1% per hundred. Direct/indirect Coombs tests
      and anti-double stranded DNA antibody were positive, her serum CH50 level was
      reduced and an increase in serum LDH isoenzyme 3 was observed. Bone marrow
      aspiration showed an almost total absence of erythroblasts and no pathological
      cell proliferation. The diagnosis of angioimmunoblastic T-cell lymphoma (AILT)
      was made based on the lymph node histological findings. Proliferation of
      arborizing small vessels with hyperplastic endothelium and infiltration of
      atypical T-lymphocytes were observed. After combination chemotherapy (THP-COP),
      remission was achieved in both the pure red cell aplasia (PRCA) and AILT.
      Remission was also accompanied by normalization of the Coombs tests, suggesting
      that autoimmune mechanisms in AILT may contribute to the development of PRCA.

PMID- 16447718
TI  - [Chronic myelomonocytic leukemia with pleural effusion as the first clinical
      sign].
AB  - We report a chronic myelomonocytic leukemia (CMML) patient whose initial symptom
      was pleural effusion, which is extremely rare. A 61-year-old male was referred to
      our hospital because of leukocytosis with blasts and pleural effusion with chest
      pain. Bone marrow examination showed trilineage dysplasia with 14% blasts and a
      normal karyotype. He was diagnosed as having MDS (RAEB) and infectious pleuritis
      on admission. Despite administration of antibiotics, leukocytosis with
      monocytosis and pleural effusion progressed rapidly. His diagnosis was then
      changed to CMML-2 and pleural infiltration due to leukemic cells expressing CD13,
      CD14 and CD33. After the leukocytosis was brought under control with
      hydroxycarbamide, the patient's pleural effusion disappeared.

PMID- 16447719
TI  - [Treatment of adult patients with aplastic anemia in Japan].

PMID- 16447720
TI  - [Evidence-based medicine for treatment of aplastic anemia in children].

PMID- 16447721
TI  - [Choice of stem cell source in hematopoietic cell transplantation].

PMID- 16447722
TI  - [EBM in the treatment of CML].

PMID- 16447723
TI  - [Diagnosis and treatment of hemophagocytic syndrome].

PMID- 16447724
TI  - [Guidelines for the diagnosis and management of multiple myeloma by the Japan
      Myeloma Study Group].

PMID- 16447725
TI  - [Development of personalized peptide vaccines for advanced cancer patients].

PMID- 16447726
TI  - [Genetic abnormalities in myelodysplastic syndrome].

PMID- 16447727
TI  - [Clinical course of 8 patients with intravascular large B-cell lymphoma diagnosed
      while alive].
AB  - We retrospectively evaluated the diagnosis and clinical courses of 8 patients
      with intravascular large B-cell lymphoma (IVL) diagnosed while they were alive.
      The median age was 67 years old (range 54 to 82). Most complaints at diagnosis
      were fever or dyspnea. All patients were in clinical stage IV with B symptoms and
      4 patients showed performance status 4. The diagnosis of IVL was confirmed by
      biopsy specimens from the bone marrow in 4, lung in 2, muscle, adrenal gland, and
      lymph node in 1 case, respectively. Initial bone marrow involvement was found in
      6 patients. Chemotherapy was performed in 7 patients. Rituximab was added to
      chemotherapy in 5 patients. Though 5 patients are alive at the median follow up
      of 12.3 months, only 1 patient is in remission. Four of 5 patients treated with
      Rituximab relapsed. In suspicious cases, it is important to bear IVL in mind and
      examine bone marrow biopsies for an early diagnosis. In addition, it is suggested
      that Rituximab may play only a temporary role in the treatment of IVL.

PMID- 16447728
TI  - [Diffuse large B-cell lymphoma with strongly positive MIB-1 stain and clinical
      features resembling Burkitt lymphoma].
AB  - A 62-year-old woman was admitted to our hospital because of gastric mucosal
      bleeding. Gastroendoscopy revealed a gastric tumor which was diagnosed from the
      biopsied specimen as diffuse large B-cell lymphoma (DLBCL). Lymphoma cells had
      infiltrated the bone marrow showed morphological features resembling Burkitt
      lymphoma (BL). Nearly 100% of the cells in the bone marrow were positive for MIB
      1 immunostaining. The chromosomal study was normal. Surface marker analysis
      disclosed that the cells were positive for CD10, CD19, CD20 and CD25. As lymphoma
      cells had infiltrated the central nervous system, combined chemotherapy was
      performed accompanied with intrathecal administration of anticancer drugs.
      Although transient improvement was observed, the patient died of the advanced
      disease three months after admission. As we have shown here, there are some cases
      of DLBCL with immunohistochemical features resembling BL. Further consideration
      about the appropriate chemotherapy program for this type of disease might be
      necessary.

PMID- 16447729
TI  - [A global perspective of neurology in Japan].
AB  - The Japanese Society of Neurology, founded in 1960, gained momentum after the
      12th World Congress of Neurology held in Kyoto (1981) and currently enjoys an
      indisputable reputation as a major contributor in the field of neuroscience.
      Clinical training, however, has fallen behind research achievements with a
      shortage of teaching staff. This necessitated the traditional, but now obsolete,
      tie to internal medicine. It is high time to seek the sovereignty of neurology as
      an independent discipline to further promote this field of medicine as advocated
      by the World Federation of Neurology. We must also participate in global affairs
      with confidence despite a perceived language barrier. It is said that science
      speaks English, which is now used universally as the official language, but from
      my vantage point, science actually speaks "broken" English in the spirit of
      international cooperation.

PMID- 16447730
TI  - [Recent advances in cerebrovascular diseases from the view point of blood
      coagulation/fibrinolysis].
AB  - Cerebrovascular diseases (CVD) are one of the most serious clinical problem in
      Japan. Here we review patho-mechanism, prevention and treatment of CVD, from the
      view point of blood coagulation/fibrinolysis and platelets. The hemostatic system
      is quite unique in the brain. One of the characteristic functional and structural
      basis of circulation is decreased expression of thromobomodulin, an anticoagulant
      endothelial protein in the brain. This may cause thrombotic tendency in the brain
      compared to other organs. Another characteristics is rich in tissue factor in the
      brain. Thus once vascular vessels are injured, circulatory factor VII may
      interact with the tissue factor and result activation of extrinsic coagulation
      pathway. Generated thrombin could not be regulated efficiently like other organs,
      because of decreased expression of thrombomodulin.

PMID- 16447731
TI  - [Neuropathology associated with dementia].
AB  - As dementing diseases are too numerous to refer to all of them, I confine my
      description to the neuropathology of amyotrophic lateral sclerosis with dementia
      (ALSD), and cerebral vascular pathology of three unique vascular diseases causing
      dementia. 1) ALSD: The cortical neuropathology of this condition exhibit two main
      unique profiles in addition to mainly temporal lobe-located cortical changes. One
      is ubiquitin-positive intraneuronal cytoplasmic inclusions, and the other a
      localized neuronal degeneration in the transitional zone between the hippocampal
      CA1 and subiculum. 2) Cerebral autosomal recessive arteriopathy with subcortical
      infarcts and leukoencephalopathy (CARASIL): The characteristic vascular change of
      this condition is marked intimal thickening of the middle and small arteries with
      relatively preserved smooth muscle cells in the media. The scalp arteries escape
      this lesion, indicating non-ischemic pathomechanisms for the baldness seen in
      this condition. 3) Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL): The main lesions of the cerebral
      vessels are smooth muscle cell degeneration of deep perforating and small
      meningeal arteries with deposition of granular osomiophilic material in the media
      of the affected vessels. 4) Sneddon syndrome: This condition characterized by
      livedo reticularis and recurrent multiple infarctions shows marked sclerotic
      changes in the deep perforating arterioles and main cerebral arteries with
      relatively spared middle- and small-sized meningeal arteries.

PMID- 16447732
TI  - [Molecular and anatomical bases of dystonia: X-linked recessive dystonia
      parkinsonism (DYT3)].
AB  - Pathological findings in dystonia have been unclear. X-linked recessive dystonia
      parkinsonism (XDP, DYT3), endemic in the Panay island, the Philippines, is
      characterized by the clinical onset with dystonia followed by parkinsonism. It
      provides a unique opportunity to explore the anatomical basis of dystonia,
      because it has discernible pathological changes even at its early phase of
      dystonia. After extensive searches for the anatomical basis in XDP, we found
      selective loss of striosomal neurons in the striatum in dystonic patients' brain.
      Because striosomal neurons inhibit nigrostriatal dopaminergic neurons via
      GABAergic innervation, the striosomal lesion could account for dopamine excess in
      the striatum, which in turn causes a hyperkinetic state or dystonia. We also
      identified the causative gene as one of the general transcription factor genes,
      TAF1. This abnormality markedly reduced the expression of dopamine D2 receptor
      gene (DRD2) in neurons. XDP has certain similarities to Huntington disease not
      only in pathological and clinical findings, but also the molecular mechanism,
      which disturbs expression of genes essential for striatal neurons, such as DRD2.
      Therapeutic intervention may become possible through pharmacological measures
      that affect gene expression.

PMID- 16447733
TI  - [Retrovirus infection and neurological disorders].
AB  - Our series of neuropathologic studies on HAM/TSP and AIDS dementia were reviewed.
      Studies on HAM/ TSP demonstrated chronic inflammatory process in the spinal cord,
      accentuated inflammation in the area with slow blood flow in the spinal cord,
      characteristic adhesion molecule expression for T-cell migration, apoptosis of
      helper T-cells in active inflammatory lesion, correlation of HTLV-I provirus
      amount with disease activity, and HTLV-I infection and expression of HTLV-I gene
      on infiltrated T-cells in the spinal cord lesion. Based on these findings, we
      have proposed a by-stander mechanism as a pathogenesis of HAM/TSP. HIV-1 also
      involves the CNS, however, its pathogenesis has not been fully studied yet. To
      understand the pathogenesis of AIDS dementia, we used a SIV-macaque model and
      demonstrated that there are two independent pathogenic processes in AIDS
      dementia; AIDS-dependent neuropil degeneration in the cortex caused by T-cell
      tropic virus, and immune response against invading virus-infected cells in the
      white matter caused by macrophage tropic virus. The latter mechanism is similar
      to that of HAM/TSP. Invasion of virus-infected blood cells inside the CNS and a
      gradual damage of surrounding CNS tissues caused by prolonged immune attack to
      these virus-infected cells may be a common pathogenic process of retrovirus
      induced CNS diseases.

PMID- 16447734
TI  - [Acute encephalopathy after ingestion of "sugihiratake" mushroom].
AB  - An outbreak of acute encephalopathy has occurred among patients with renal
      dysfunction after ingestion of "sugihiratake" mushroom (angel's wings mushroom)
      in the northern area of Japan between the end of September and the middle of
      October in 2004. Most of the patients had varying degree of renal dysfunction.
      Patients initially presented with asthenia in legs, shaking limbs, and difficulty
      in ambulation. Several days later, tremor-like involuntary movements or myoclonus
      developed, which were frequently followed by intractable status epilepticus.
      Eleven patients were dead. CSF examination showed elevated protein levels without
      pleocytosis. Brain CT and MRI studies revealed abnormal signal intensities in
      bilateral external capsule and claustrum, and in the cortical white matter. All
      of the patients had a history to have ingested sugihiratake in varying quantities
      and frequencies prior to the onset of the illness. Although no similar patients
      have been reported in the past, this edible mushroom must have induced acute
      toxic encephalopathy. The characteristic features of clinical signs and symptoms,
      and laboratory findings of this encephalopathy were briefly summarized.

PMID- 16447735
TI  - [MSA update].
AB  - Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder
      characterized by various combinations of parkinsonism, cerebellar ataxia and
      autonomic failure. Although the clinical entities of olivopontocerebellar
      atarophy (OPCA), striatonigral degneratin (SND) and Shy-Drager syndrome have been
      conventionally used, recent identification of oligodendroglial cytoplasmic
      inclusions (GCIs) as the pathognomonic findings has established the
      clinicopathological entity of MSA. Epidemiological studies in Japan have shown
      that MSA is the most common form of sporadic ataxia. Among the various clinical
      forms of MSA, OPCA has been shown to be the most common form. Although MSA has
      been regarded as a sporadic disease, familial occurrence has recently been
      identified. Integrated analyses of non-parametric linkage analyses on the
      familial MSA cases and association studies on sporadic MSA cases are expected to
      accelerate the studies on identification of genes involved in the pathogenesis of
      MSA.

PMID- 16447736
TI  - [An old and new focal symptom, hypothalamus and hypersomnia, orexin system and
      narcolepsy].

PMID- 16447737
TI  - [Myotonic dystrophy as an RNA-mediated disease].

PMID- 16447738
TI  - [Clinical applications of transcranial magnetic stimulation for the treatment of
      various neurological diseases].
AB  - Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential
      therapeutic tool in various neurological and psychiatric diseases including
      depression, Parkinson disease, spinocerebellar degeneration, epilepsy, urinary
      incontinence, movement disorders, chronic pain, migraine and chronic tinnitus,
      etc. Several reports showed the therapeutic effects of rTMS as a treatment of
      depression and Parkinson disease (PD), whereas others found no significant
      effects. It is by now not yet fully understood whether rTMS has a therapeutic
      effect on those diseases. The controversy arises from the differences of the
      stimulation parameters and evaluation methods of the effects in those studies.
      The Japanese multi-center, double blinded, sham stimulation controlled trial in
      85 patients with PD showed an efficacy in both the rTMS-treated and sham
      stimulated patients. This result does not prove the efficacy of the rTMS in PD;
      on the other hand, it does not rule out the efficacy. Possible mechanism of
      favorable effects of rTMS is related to increasing the release of dopamine in the
      mesolimbic and mesostriatal system. The other Japanese multi-center, double
      blinded, sham stimulation controlled trial in 99 patients with spinocerebellar
      degeneration revealed significant therapeutic effects of rTMS in 51 patients with
      SCA6. We studied the effects of rTMS on seizure susceptibility in rats which
      prevented the development of status epilepticus of pentylenetetrazol-induced
      convulsions. This finding suggests the possibility of therapeutic use of rTMS in
      epilepsy. Further studies should be performed aiming to reveal the optimal
      stimulation parameters, and are necessary to reveal the therapeutic role of the
      rTMS in neurological and psychiatric diseases.

PMID- 16447739
TI  - [Migraine-update--current concepts of migraine pathogenesis].
AB  - The pathophysiology of migraine still remains unclear. However, abundant evidence
      in support of the view that migraine as an illness of the central nervous system
      has been accumulated. First, the hyperexitability in the brain is recognized even
      in the stage between attacks in migraineurs according to findings of transcranial
      magnetic stimulation techniques, MRI-BOLD studies or 31P SPECT examinations.
      Second, cortical spreading depression originating in the occipital cortex is more
      likely to be related to the aura. Third, sensitization of the trigeminal nerve
      system is substantially involved in process of headache pain in migraine. Fourth,
      clonic dysfunction of the priaqueductal gray matter in the brain stem may
      underlie the migraine pathogenesis. Thus, current concept of susceptibility of
      migraine is attributed to certain dysfunction of the deep brain structures such
      as the brain stem rather than the blood vessels in the brain or dura mater.

PMID- 16447740
TI  - [Diagnostic criteria of neurosarcoidosis].
AB  - We have collaborated with Japanese Sarcoidosis Society and Japanese Society of
      Respiratory diseases to make a new diagnostic criteria of neurosarcoidosis.
      (definite) Having positive clinical findings which suggest a neurosarcoidosis.
      Pathology proven case. (probable) Having positive clinical findings which suggest
      a neurosarcoidosis. Pathology proven in other organ. Elevated serum ACE or BHL
      demonstrated by chest XP or CT scan. (possible) Having positive clinical findings
      which suggest a neurosarcoidosis. Elevated serum ACE or BHL demonstrated by chest
      XP or CT scan. CNS sarcoidosis, sarcoid neuropathy and sarcoid myopathy are
      separately diagnosed. To evaluate our criteria, about 100 papers on
      neurosarcoidosis published worldwide in these 6 years were retrospectively
      examined. Our criteria showed a better results than 1988 criteria (former
      Japanese criteria) and Zajicek's criteria which was published in 1999 (QJ Med 92:
      103). Point is there is no more need to depend upon Kveim reaction which is time
      consuming, not so specific and difficult to obtain its antigen. Our new criteria
      is calculated to be sensitivity of 78-98% (BHL or ACE), and specificity of 83-99%
      (ACE). Because of their low specificity, Gallium scintigraphy and broncho
      alveolar lavage fluid examination are excluded from our diagnostic criteria,
      however, their high sensitivity are still useful to begin with.

PMID- 16447741
TI  - [Stroke in young adults in Japan].
AB  - The details of stroke in young adults remain unknown in Japan. We performed a
      multicenter survey to establish a stroke data bank for young adults in Japan. We
      collected clinical data of 7,245 acute stroke patients admitted to 18 hospitals
      in Japan. In patients admitted within the first 7 days of stroke, patients aged =
      < 50, = < 45, and = < 40 accounted for 8.9%, 4.2%, and 2.2%, respectively.
      Hypertension, diabetes mellitus, hypercholesterolemia, and non-valvular atrial
      fibrillation were significantly more frequent in the non-young than in the young,
      but smoking habits and patent foramen ovale were more frequent in the young than
      in the non-young. Brain infarction was the most predominant stroke subtype in the
      non-young, but not so in the young (62.6% vs. 36.7%, p < 0.01). Brain hemorrhage
      (20.8% vs. 32.1%, p < 0.01) and subarachnoid hemorrhage (7.3% vs. 26.1%, p <
      0.01) were more frequent in the young. Causes of brain infarction and hemorrhage
      were often atypical in the young (2.8% vs. 25.1%, p < 0.001 and 4.6% vs. 20.2%, p
      < 0.0001, respectively). Causes of stroke in the young was often atypical, such
      as cerebral arterial dissection, Moyamoya disease, antiphospholipid syndrome,
      arteriovenous malformation, et al. Because causes and underlying risk factors of
      stroke in young adults were quite different from those in older patients, we need
      to establish the data bank and to explore optimal measures of the diagnosis and
      management for young stroke patients.

PMID- 16447742
TI  - [Cerebral arterial dissection].
AB  - We investigated a total of 98 cases with stroke caused by cerebral arterial
      dissection recruited in Strategies against Stroke Study for Young Adults in Japan
      (SASSY-Japan). The most frequent site of dissection was the intracranial
      vertebrobasilar artery. The stroke subtype was divided into ischemic (TIA and
      cerebral infarction) and hemorrhagic types (subarachnoid hemorrhage). The
      ischemic type was predominant (69%) and patients with the ischemic type were
      younger than those with the hemorrhagic type (P < 0.01). In the intracranial
      arterial dissection, nearly all cases were of the ischemic type. In contrast, in
      the extracranial arterial dissection, 60% of cases were ischemic and 40% were
      hemorrhagic. Cerebral angiography was the most important diagnostic procedure in
      the hemorrhagic type. In the ischemic type, MRI and MRA were more frequently used
      to show the findings specific to the dissection such as an intimal flap or double
      lumen and intramural hematoma. The outcome at discharge is generally good such
      that the modified Rankin Score was among 0-II in 69% of cases. However, in the
      hemorrhagic type, recurrence during an acute stage was frequent, and the outcome
      was poor with a mortalit rate of 19%. The establishment of an effective
      intervention to prevent the recurrence of subarachnoid hemorrhage is urgently
      required.

PMID- 16447743
TI  - [Paradoxical brain embolism].
AB  - Although paradoxical brain embolism result in the right-to-left shunt (RLS) is
      very important etiology of ischemic stroke especially in young adults, the
      detailed characteristics of them in Japan remain unknown. In collected clinical
      data for 7,245 acute stroke patients, patent foramen ovale (PFO) were more
      frequent in the young patients group (n = 1,584) than in the non-young patients
      group (n = 5,661) (0.7% vs. 1.2%, p = 0. 07). The frequency of PFO was rare than
      that of previously reported. Suspected reason is that the limited patients were
      underwent transesophageal echocardiography (TEE). The golden standard to detect
      RLS is contrast-enhanced TEE, and standardization of procedure is the most
      important factor. In our hospital, positive rate of RLS was risen up to 21.9%
      from 8.8% by standardization. In the patients with RLS in our hospital, the
      definite and probable criteria of paradoxical brain embolism were fulfilled only
      in 7.7% and 38.5%, respectively. If patients have any other risk factors (e.g.
      venous thrombus, cardiac source of embolism), to prevent recurrent stroke
      associated with RLS they must be underwent anticoagulation and correctly
      controlled by PT-INR. And if patients have no other risk factors, PICCS study
      confirmed that there was no difference of recurrence rate between anticoagulation
      and aspirin therapy.

PMID- 16447744
TI  - [Antiphospholipid syndrome and stroke].
AB  - Antiphospholipid syndrome is characterized by arterial or venous thrombosis, and
      the presence of antiphospholipid antibodies (aPL). APL are considered to be a
      cause of an acquired hypercoagulable state leading to stroke and transient
      ischemic attack (TIA). We examined the causes in 50 young patients with ischemic
      stroke. The most prevalent cause was atherosclerosis and the incidence of APS was
      12.5%. APL comprise a heterogeneous group of autoantibodies, such as beta2
      glycoprotein I dependent anticardiolipin antibody (beta2-GPIaCL), lupus
      anticoagulant (LA), and other antiphospholid-protein antibodies. We examined the
      incidence and the pathogenic role of antiphospholipid protein antibodies. The
      subjects comprised 250 patients (155 male, 95 females) with ischemic stroke, aged
      26 to 92 years (mean 72 years). We measured beta2-GPI aCL, IgG aCL, LA,
      phosphatidyserine dependent antiprothrtombin antibody (PS-PT), antiphosphatidyl
      serine antibody (PS), antiphosphatidyl-inositol antibody (PI) in each patient.
      The incidence of beta2-GPI aCL, IgG aCL, LA, phosphatidyserine, PS-PT, PS, and PI
      was 2.8%, 12%, 9.2%, 7.2%, 9.6%, and 8.8%, respectively. The incidence of young
      stroke patients under 50 years was 5.2%. Among 13 young stroke patients, 5 had
      SLE. Among 23 patients with LA., 18 (78%) patients had PS-PT. Anti-PS-PT antibody
      is closely related to LA. Antinuclear antibody was detected in 79% of the
      patients with aPS and/or aPI. We compared the carotid ultrasonographic findings
      in positive aPI or aPS patients with those in negative ones. Increased IMT,
      plaque score and carotid stenosis were more common in aPI and aPS-positive
      patients than in negative ones Three of 5 patients who showed positive beta2-GPI,
      aCL and LA, simulataneously, had sysyemic lupus erythematosus as an immulological
      background. Two of 3 patients with PI and/or PS and beta2-GPI and/or LA were
      patients with SLE. Antiphospholipid antibody was considered to be a risk factor
      of stroke, especially in SLE and/or young female patients. The incidence of lupus
      anticoagulant is more common than beta2-GPI aCL in ischemic stroke. In SLE
      patients with stroke, multi-antiphospholipid-protein antibodies was inclined to
      be present. LA is closely related to ant-PS-PT and aPI and aPS are associated
      with anti-nuclear antibody and precipitation of atherosclerosis.

PMID- 16447745
TI  - [Perspective of dementia therapy].
AB  - As growing population of the elderly over 65 years of age, dementia will be one
      of the most important diseases in Japan. To defeat the dementia, the following
      strategies would be needed; 1) acceleration of basic research for dementia, 2)
      acceleration of clinical research for dementia, 3) development of care system for
      patients with dementia, and 4) provision of social basis for the elderly. On the
      basis of an understanding of the pathophysiology, treatments of Alzheimer's
      disease includes the following components: antiamyloid therapies including
      secretase inhibitors, metal binding agents and Abeta vaccine, neuroprotective
      strategies, cholinesterase inhibitors, memantine, immunotherapy including Abeta
      vaccine, anti-inflammatory therapy, hormone-replacement therapy,
      psychopharmacologic agents, nonpharmacologic interventions and health maintenance
      activities, and an alliance between clinicians and family members and other
      caregivers responsible for the patient. The combination therapies with
      pharmacologic and nonpharmacologic components are probably useful for patients
      with Alzheimer disease or other dementia. In addition, development of accurate
      diagnostic methods of dementia and the early detection system of amyloid in the
      brain are expected. Responsibility of neurologist for dementia is getting
      important next 10 years in Japan.

PMID- 16447746
TI  - [New therapeutic strategies for behavioral and psychological symptoms of
      dementia].
AB  - Interventional studies, with the aim of reducing the burden of care through drug
      or non-drug therapies of behavioral and psychological symptoms of dementia
      (BPSD), have been scarce. However, we are now able to do pharmacological
      management for BPSD with new drugs such as atypical neuroleptics, SSRIs, and
      cholinesterase inhibitors. Delusions of theft are one of the most frequently
      observed BPSD in patients with AD. In addition, the delusions and ensuing
      aggression and anxiety are major factors that increase the burden of caregivers.
      Delusions of theft in patients with AD were eliminated or reduced with low-dose
      atypical neuroleptics (risperidone). This significantly reduced the burden of
      care overall for caregivers. New therapeutic strategies such as cholinesterase
      inhibitors for visual hallucinations in DLB and SSRIs for overeating and
      stereotyped behavior in FTLD might also remarkably reduce the burden of care for
      these patients. For many dementia patients, there are still no drugs that offer a
      principal cure. It is, therefore, important to evaluate their BPSD correctly at
      the earliest possible time, so that the burden of caring can be reduced through
      appropriate drug treatment. This reduction is critical for the continuation of
      satisfactory at-home care and might contribute to the health economics.

PMID- 16447747
TI  - [Cognitive rehabilitation for Alzheimer disease--the learning therapy].
AB  - We propose a new intervention program, the concept of which is derived from the
      knowledge of both brain science and clinical studies. We set up a hypothesis that
      activation of the association cortices by cognitive tasks may well improve the
      function of these cortices. To choose effective cognitive tasks for activation of
      the association cortices, we reviewed previous neuroimaging studies. Then, we
      prepared two tasks in arithmetic and Japanese language, which were systematized
      basic problems in reading and arithmetic, for the training program. Sixteen
      experimental and 16 control subjects participated. The subjects of the
      experimental group were asked to perform a training program using learning tasks
      in reading and arithmetic. The function of the frontal cortex of the subjects was
      assessed by FAB (frontal assessment battery at bedside). After six months of
      training, the FAB score of the experimental group showed a statistically
      significant improvement. We also observed the restoration of communication and
      independence, and improvement in relationships with the clinical staff in the
      experimental group. Our results indicate that learning tasks of reading aloud and
      arithmetic calculation can be used for cognitive rehabilitation, which improves
      frontal functions, of dementia patients.

PMID- 16447748
TI  - [Abeta vaccine therapy for Alzheimer's disease].
AB  - In 1999, Schenk et al reported that vaccination of PDAPP-transgenic mice with
      synthetic Abeta42 in complete Freund's adjuvant showed markedly decrease of the
      amyloid burden in the brain. The second trial of vaccine, AN1792, for Alzheimer's
      patients was halted because of meningoencephalitis found in 6% of patients and
      one autopsy case was reported. Here, we comment the methods and the immunological
      mechanisms of Abeta vaccine therapy and discuss the pathological changes in the
      brain and side effects after AN1792 treatment. Furthermore, we present an oral
      Abeta vaccine therapy for Alzheimer's disease with the recombinant adeno
      associated virus (AAV) vector that we developed.

PMID- 16447749
TI  - [Identification of neural stem cells in adult human brain: its implication in the
      strategy for repairing the damaged central nervous system].
AB  - Neural stem cells (NSCs) ar self-renewing, multipotential progenitor cells. A
      single NSC can give rise to a wide variety of CNS cells, including neurons,
      astrocytes, and oligodendrocytes. Because of these characteristics, there is an
      increasing interest in NSCs and neural progenitor cells, both from a basic
      developmental biology perspective and from a clinical one that is aimed at
      developing therapeutic applications for the damaged brain. Current research into
      the nature of the NSCs present in the CNS includes the study of the extracellular
      factors and signal transduction cascades involved in their differentiation and
      maintenance, their population dynamics, and their localization in the embryonic
      and adult brain. These lines of research, combined with other studies intended to
      permit the prospective identification and isolation of NSCs, and their induction
      into particular neuronal phenotypes--which will be introduced in my talk--should
      lead to the development of feasible strategies for manipulating NSC cells in situ
      to treat the damaged brain and spinal cord injury.

PMID- 16447750
TI  - [Transplantation of neural stem cells for spinal cord injury].
AB  - Neural progenitor cells, including neural stem cells (NSCs), are an important
      potential graft material for cell therapeutics of damaged spinal cord. Here we
      used as a source of graft material a NSC-enriched population derived from human
      fetal spinal cord (Embryonic week 8-9) and expanded in vitro by neurosphere
      formation. NSCs labeled with BrdU (TP) or culture medium (CON) were transplanted
      into the adult marmoset spinal cord after contusion injury at C5 level. Grafted
      NSCs survived and migrated up to 7 mm far from the lesion epicenter. Double
      staining with TuJ1 for neuron, GFAP for astrocyte, or CNPase for oligodendrocyte
      and BrdU revealed that grafted NSCs differentiated into neurons and
      oligodendrocytes 8 weeks after transplantation. More neurofilaments were observed
      in TP than those of CON. Furthermore, behavioral assessment of forelimb muscle
      strength using bar grip test and amount of spontaneous motor activity using
      infrared-rays monitoring revealed that the grafted NSCs significantly increased
      both of them compared to those of CON. These results indicate that in vitro
      expanded NSCs derived from human fetal spinal cord are useful sources for the
      therapeutics of spinal cord injury in primates.

PMID- 16447751
TI  - [Future views and challenges to the peripheral nerve regeneration by cell based
      therapy].
AB  - Chronic degenerative diseases and traumatic injuries are responsible for a
      decline in neuronal function. Cell transplantation is one of the strategies with
      potential for treatment of such neural disorders, and many kinds of cells
      including embryonic stem cells and neural stem cells have been considered as
      candidates for transplantation therapy. Bone marrow stromal cells (MSCs) have
      great potential as therapeutic agents since they are easy to isolate and can be
      expanded from patients without serious ethical and technical problems. We found a
      method for the highly efficient and specific induction of functional neurons,
      skeletal muscle cells and Schwann cells from both rat and human MSCs. Induced
      neurons and Schwann cells were transplanted to animal models of Parkinson's
      disease, stroke, peripheral nerve injury, and spinal cord injury, resulting in
      the successful integration of transplanted cells and improvement in behavior of
      transplanted animals. Induced skeletal muscle cells differentiate into muscle
      fibers upon transplantation into degenerated muscles of rats and mdx-nude mice.
      The induced population contained Pax7-positive cells that contribute to
      subsequent regeneration of muscle upon repetitive damage without additional
      transplantation of cells. Here we focus on the respective potentials of MSC
      derived cells and discuss the possibility of clinical application in
      neurodegenerative and muscle degenerative diseases.

PMID- 16447752
TI  - [Regenerative medicine of skeletal muscle].
AB  - In the dystrophin-deficient mdx mice, an animal model of Duchenne muscular
      dystrophy (DMD), damaged skeletal muscles are efficiently regenerated and thus
      the animals thrive. The phenotypic differences between DMD patients and mdx mice
      suggest the existence of factors that modulate the muscle wasting in the mdx
      mice. To identify these factors, we searched for mRNAs affected by the mdx
      mutation using cDNA microarrays with newly established skeletal muscle cell lines
      derived from mdx and normal mice. We found that genes encoding thymosin beta4,
      frizzled related protein 2 (FRP2), and regeneration-associated muscle protease
      (RAMP) are up-regulated in skeletal muscle of mdx mice. Thymosin beta4 was
      induced in both regenerating muscle fibers and inflammatory cells after muscle
      injury. It stimulated migration and chemotaxis of myoblasts. FRP2 was
      dramatically induced upon muscle injury. RNA interference-mediated knockdown of
      FRP2 mRNA in myoblasts resulted in a massive cell death. Thus FRP2 may enhance
      the survival rate of myoblasts in the regenerative regions. RAMP mRNA was
      specifically induced in the regenerating areas of injured skeletal muscle.
      Expression of RAMP and FRP2 was much lower in individual muscle cell lines
      derived from biopsy specimens from several DMD patients compared to in a normal
      muscle cell line. Above results suggest that thymosin beta4, FRP2, and RAMP may
      play roles in the regeneration of skeletal muscle and that down-regulation of
      these molecules could be involved in the progression of DMD in humans.

PMID- 16447753
TI  - [West Nile fever and West Nile encephalitis].
AB  - West Nile virus is a mosquito-borne flavivirus, and maintained in mosquito-bird
      cycle in nature. Humans are a dead-end host in West Nile virus infection.
      Symptoms are developed in approximately 20% of West Nile virus-infected humans.
      Encephalitis and meningitis are developed in about 1 out of 150 infected humans,
      especially in elderly populations. It has recently been reported that West Nile
      virus causes polio-like, acute flaccid paralysis and polyneuritis. These symptoms
      occur in patients without central nervous system symptoms as well as in those
      with encephalitis. Thus, West Nile virus causes various types of illness in
      humans. West Nile virus has not entered Japan yet. However, West Nile virus
      should be considered to be one of the causative agents for patient with a febrile
      illness, meningitis, encephalitis or acute flaccid paralysis who came back from
      West Nile endemic or epidemic areas of the world.

PMID- 16447754
TI  - [HIV encephalopathy].
AB  - HIV encephalopathy is one of the complexified viral diseases. In the infected
      brains, HIV-infection is restricted in macrophages and microglia although its
      damage extends to neurons and oligodendrocytes. Accumulating evidences have
      suggested that many viral and host factors are involved in this disease. However,
      its precise mechanism is still unsolved. To examine the mechanism of the disease,
      we developed an HIV-1-infected human cell-transplanted mouse model and TNF
      related apoptosis-inducing ligand was identified as a neurotoxic host factors in
      HIV-infected brain. Next, we examined the neurotoxic host factors using co
      culture system with macrophage-tropic HIV-1-infected macrophages as followings:
      Target brain cells are murine neuron/glia mixed culture, murine neurospehre
      forming culture and rat brain hippocampus slice culture. In these systems,
      neurons and neural stem cells were preferentially damaged. On the other hand, we
      also identified two anti-HIV genes, CD 14 and CD63 (dN), which inhibit HIV-1
      induced cytotoxicity using a lentiviral screening system. Because they express on
      monocyte or activated macrophage and microglia, these results suggest that CXCR4
      using HIV-1 cannnot expand inside of brain. We also extended the screening system
      to identify the host factors which protect against HIV-1-induced encephalopathy.
      Our study will contibute to development of new therapeutic strategy for HIV
      encephalopathy as well as other CNS diseases.

PMID- 16447755
TI  - [Parasitic diseases in the central nervous system].
AB  - Along with the drastic decrease of soil-transmitted intestinal helminthiases,
      parasitic diseases in general are ignored, or considered as the disease of the
      past, in Japan. However, due to the Japanese food culture of eating raw
      materials, food-borne parasitic diseases are still present in Japan. The majority
      of food-borne parasitic diseases are zoonotic, and caused by ectopic migration of
      parasite larvae. They accidentally migrate into CNS to cause deleterious
      conditions. Clinicians should always remind about the possibility of parasitic
      diseases when they make differential diagnosis for CNS diseases.

PMID- 16447756
TI  - [Inter- and intraindividual pharmacokinetic variations in the treatment of
      Parkinson's disease].
AB  - In the treatment of Parkinson's disease, levodopa, DCI, MAO-B inhibitor, COMT
      inhibitors, dopamine receptor agonists, amantadine, anticholinergics have been
      applied and new drugs are being developed. Levodopa is still the golden standard
      in the treatment of Parkinson's disease. The study on levodopa bioavailability
      showed 3-4 times differences in individual patients. Drug-food interactions are
      prominent in levodopa. Low protein food increased levodopa bioavailability and
      improved no ON or delayed ON in the treatment of Parkinson's disease. Vitamine C
      or magnesium did not alter the bioavailability of levodopa. The bioavailability
      of levodopa between the levodopa/carbidioa (100/12.5) group and the
      levodopa/benserazide (100/25) group was studied in patients with Parkinson's
      disease by population PK study. C(max) of levodopa in levodeopa/benserazide group
      was twice as high as in levodopa/carbidopa group. Domperidone, a dopamine
      receptor antagonist applied as an antiemetic inceases vowel movement. The effect
      of domperidone on levodopa bioavailability was studied, and the combination of
      domperidone with levodopa increased AUC of levodopa. Clarythromycin or grape
      fruit juice inhibits both of CYP3A4 and P-glycoprotein which work on metabolism
      and absorption of drugs. Coadministration of clarythromycin with ergot alkaloids
      such as cabergoline or bromocriptine increased the AUC up to 2-3 times.
      Amantadine is excreted through kidney without being metabolized and renal
      function is the most important factor in the blood concentration of amantadine.
      In elder women with the body weight of 50 kg or less, creatinine clearance is
      less than 50 ml/min even though the serum creatinine is within the normal range.
      Selegiline is metabolized through CYP2D6 and 3A4. Coadministration of qunidine,
      cimetidine, maclorides, antifungals, grape fruit juice increase the
      bioavailability of selegiline and may augment the antiparkinsonian effect.

PMID- 16447757
TI  - [Pathogenesis of Parkinson's disease: implications from familial Parkinson's
      disease].
AB  - The deposition of alpha-synuclein (aS), a product of pathogenic gene for
      dominantly inherited familial Parkinson's disease (PD; park1), as fibrillary
      aggregates like Lewy bodies (LB), is a hallmark lesion of a set of
      neurodegenerative disorders termed synucleinopathies, including sporadic PD and
      dementia with Lewy bodies (DLB). We found that aS is the major component of LBs
      and further identified a specific phosphorylation of Ser129 of insoluble aS by
      mass spectrometric analysis. The roles of DJ-1 and PINK-1, products of pathogenic
      genes for autosomal recessive forms of early-onset parkinsonism, have
      subsequently been examined. Overexpression of DJ-1 conferred cultured cells
      resistance to oxidative stress, suggesting an antioxidant function of DJ-1. We
      also confirmed the anti-PTEN function of DJ-1 that may promote cell survival,
      showing decreased phosphorylation of Akt through upregulation of PTEN activity
      upon siRNA knockdown for DJ-1. PINK-1, that had been identified as a gene
      upregulated by PTEN overexpression, turned out to be a protein kinase localized
      in mitochondria. Collectively, information derived from studies on pathogenic
      genes for familial PD will open up the way toward the clarification of the
      pathogenesis of PD, underscoring the roles of protein aggregation, proteolysis,
      oxidative stress and protein phosphorylation in PD.

PMID- 16447758
TI  - [Gene therapy and cell transplantation for Parkinson's disease].
AB  - Increasing enthusiasm in the field of stem cell research is raising the hope of
      novel cell replacement therapies for Parkinson's disease (PD), but it also raises
      both scientific and ethical concerns. In most cases, dopaminergic cells are
      transplanted ectopically into the striatum instead of the substantia nigra. If
      the main mechanism underlying any observed functional recovery with these cell
      replacement therapies is restoration of dopaminergic neurotransmission, then
      viral vector-mediated gene delivery of dopamine-synthesizing enzymes is a more
      straight forward approach. The development of a recombinant adeno-associated
      viral (AAV) vector is making gene therapy for PD a feasible therapeutic option in
      the clinical arena. Efficient and long-term expression of genes for dopamine
      synthesizing enzymes in the striatum restored local dopamine production and
      allowed behavioral recovery in animal models of PD. A clinical trial to evaluate
      the safety and efficacy of AAV vector-mediated gene transfer of aromatic L-amino
      acid decarboxylase, an enzyme that converts L-dopa to dopamine, is underway. With
      this strategy patients would still need to take L-dopa to control their PD
      symptoms, however, dopamine production could be regulated by altering the dose of
      L-dopa. Another AAV vector-based clinical trial is also ongoing in which the
      subthalamic nucleus is transduced to produce inhibitory transmitters.

PMID- 16447759
TI  - [Pathogenesis of Parkinson's disease: a common pathway between alpha-synuclein
      and parkin and the mechanism of Lewy bodies formation].
AB  - Parkin, a product of Park2 gene, is an important player in the pathogenic process
      of Parkinson's disease (PD). Despite numerous studies including search for the
      substrate of parkin, the mechanism by which loss-of-function of parkin induces
      selective dopaminergic neuronal death remains unclear. Here we show that
      antisense knockdown of parkin causes apoptotic cell death of human dopaminergic
      SH-SY5Y cells associated with caspase activation and accompanied by accumulation
      of oxidative dopamine (DA) metabolites due to auto-oxidation of DOPA and DA.
      Forced expression of alpha-synuclein (alpha-SN), another familial PD gene
      product, prevented accumulation of oxidative DOPA/DA metabolites and cell death
      caused by parkin loss. Our findings indicate that both parkin and alpha-SN share
      a common pathway in DA metabolism whose abnormality leads to accumulation of
      oxidative DA metabolites and subsequent cell death. In addition, we identified a
      phosphorylated form of IkappaBalpha (pIkappaBalpha), an inhibitor of the NF
      kappaB signaling pathway, and the components of the SCF(beta-TrCP), ubiquitin
      ligase of pIkappaBalpha, are novel protein components in LBs. Subsequently, we
      showed those proteins are included in the ubiquitin-LB-like inclusions generated
      by treatment of a proteasome inhibitor. Furthermore, the generation of the
      inclusions are independent on cell death due to impairment of the proteasome.

PMID- 16447760
TI  - [Synthetic glycolipid ligands as novel therapeutics for multiple sclerosis].
AB  - Our previous works indicate that regulatory cells such as natural killer (NK)
      cells and NKT cells could play an active role in maintaining the remission state
      of MS. We have therefore adopted a strategy for developing the future MS therapy
      by targeting NKT cells. The unique glycolipid-reactive lymphocytes are known to
      produce a large quantity of Th2 cytokines such as IL-4 when encountering their
      ligands like alpha-galactosylceramide (alpha-GC). Whereas most of the NKT ligands
      so far described would stimulate both Th1 and Th2 cytokine production by NKT
      cells, the synthetic compound OCH, an analogue of alpha-GC with a shorter lipid
      tail, is the one which selectively induces IL-4 production. Given this property,
      oral or intraperitoneal OCH administration would prohibit the development of a
      variety of Th1-meediated pathology, including EAE, collagen-induced arthritis,
      type 1 diabetes, DSS-induced colitis and acute GVHD by inducing Th2 bias. This
      review paper summarizes the recent publications and our unpublished results
      related to the efficacy of OCH and to the molecular mechanism accounting for the
      Th2 inducing property of OCH.

PMID- 16447761
TI  - [Multiple sclerosis].
AB  - Longitudinally extensive spinal cord lesions that extend over three vertebral
      segments on magnetic resonance imaging (MRI) are significantly more common in
      opticospinal multiple sclerosis (OSMS) than in conventional MS (CMS) in Japanese.
      In Japanese patients with MS, concentrations of serum vascular endothelial growth
      factor (VEGF) were significantly higher in MS patients in relapse than in
      controls or MS patients in remission, irrespective of clinical subtype. VEGF at
      relapse showed a significant positive correlation with the length of the spinal
      cord lesions on MRI. The IL-17/IL-8 system in cerebrospinal fluid (CSF) was
      markedly activated in OSMS, and both cytokines correlated with CSF/serum albumin
      ratio and the spinal cord lesion length on MRI. IL-17 is produced by autoreactive
      memory T cells and induces IL-8 production in a variety of cells. IL-8 acts as a
      chemokine for neutrophils as well as T cells. In autopsied spinal cords from OSMS
      patients, many neutrophils were seen to infiltrate the severely damaged spinal
      cord lesions; something that might be explained by intrathecal activation of IL
      17/IL-8 axis in this condition. Our results, therefore, suggest that an increase
      in both serum VEGF and CSF IL-17 and IL-8 might contribute to the formation of
      longitudinally extensive spinal cord lesions through an increase of vascular
      permeability and the reinforcement of neutrophilic inflammation.

PMID- 16447763
TI  - [Neuroimaging for surgical treatment of epilepsy].
AB  - Imaging of interictal 18F-FDG PET and ictal SPECT is useful for identifying
      regions of seizure in epilepsy. Epileptic foci usually show decreased and
      increased flow/metabolism in the interictal and ictal phase respectively. A
      fusion technique of high resolution PET and MRI has become indispensable to
      preoperative evaluation for epileptic surgery. Subtraction ictal SPECT
      coregistered to MRI (SISCOM) is also an useful technique for localizing
      significant flow increase in the focus. Central type benzodiazepine receptor
      imaging using 11C-flumazenil PET or 123I-iomazenil SPECT is an alternative and
      sensitive technique for localizing epileptogenic regions. This receptor imaging
      delineates epileptic foci more precisely than 18F-FDG PET. There has been
      considerable interest in the role that functional magnetic resonance imaging
      (fMRI) may play in the assessment of patients with epilepsy. The application of
      fMRI paradigms used in cognitive neuroscience to patients with epilepsy is
      complicated. Although fMRI is increasingly being used clinically to establish
      language dominance, further work is required to localize accurately those
      specific language functions that are most at risk following surgery. Memory
      paradigms are not yet validated for use in surgical planning, although
      methodological and technical advances should make this possible in the near
      future.

PMID- 16447762
TI  - [Chronic progressive cervical myelopathy with HTLV-I infection: variant form of
      HAM/TSP].
AB  - We report four patients with slowly progressive cervical myelopathy. The four
      patients had several features in common; 1) progressive cervical myelopathy with
      a duration of several months to years, 2) abnormal lesions in the cervical to
      upper thoracic cord levels with or without gadolinium enhancement, 3) anti-HTLV-I
      antibodies were positive both in serum and CSF, 4) high levels of HTLV-I proviral
      load in PBMC. The calculated risk of HAM/TSP in two patients showed a high value,
      comparable to those of HAM/TSP, and higher than those of healthy HTLV-I carrier.
      Because the clinical and laboratory findings of these four cases show
      similarities to those of HAM/TSP, we propose that these four cases may be a
      variant form of HAM/TSP.

PMID- 16447764
TI  - [Surgical treatment for extratemporal lobe epilepsy].
AB  - We analyzed the seizure outcome of 140 patients who underwent resective surgeries
      of extratemporal lobes including multilobar resection and hemispherectomy. The
      patients were followed for 2.0 to 16.7 years after surgery (mean, 6.2 years). The
      overall seizure outcome was Engel's class I in 87 patients (62%), class II in 14
      (10%), class III in 13 (9%), and class IV in 26 (19%). The proportion of class I
      cases was 76% in 71 patients with discrete lesions under 5 cm in diameter on MRI,
      whereas the proportion was 52% in 46 patients with widespread lesions over 5 cm,
      and 39% in 23 patients with no MRI-detectable lesion. The seizure-free rates of
      extratemporal lobe resection was slightly lower compared with temporal lobe
      resection. Even in patients with extratemporal lobe epilepsies, clinicians should
      consider the option of surgical intervention from the early stage of disease.

PMID- 16447765
TI  - [Newer treatment of epilepsy--brain pacemakers and transcranial magnetic
      stimulation].
AB  - The antiepileptic medication and surgical treatment had brought many patients
      with epilepsy to be seizure free, however, one third of the patients continue to
      experience seizures. There has recently been an explosion of research into brain
      stimulation for treating these intractable epilepsy patients. This is largely due
      to the success of deep brain stimulation of movement disorders. The intelligent
      cardiac pacemakers also stimulated the neurosurgeons to utilize the implantable
      devices. In this paper, brain stimulations with vagus nerve stimulator (VNS),
      depth electrodes, subdural electrodes, external responsive neuro-stimulator,
      implantable brain stimulator and transcranial magnetic stimulator are reviewed.
      The VNS had been approved in Europe and United States for clinical use. The
      efficacy of the VNS has already proven by the controlled trials. Stimulation of
      the thalamus, subthalamic nucleus and hippocampus showed some efficacy in a small
      number of patients, however, large scale traials remains to be undertaken.
      External responsive neurostimulator has shown efficacy and safety to justify
      further studies with implantable brain stimulators. The multi-center cooperative
      study is ongoing in the US to examine the usefulness of the implantable
      stimulator. Animal studies showed efficacy of the transcranial magnetic
      stimulation for the treatment and prevention of the seizures and status
      epilepticus.

PMID- 16447766
TI  - [Alpha-dystroglycanopathy (FCMD, MEB, etc): abnormal glycosylation and muscular
      dystrophy].
AB  - Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and
      muscle-eye-brain (MEB) disease are similar disorders characterized by congenital
      muscular dystrophy, brain and eye anomalies. We previously identified the genes
      for FCMD and MEB, which encode fukutin and POMGnT1. Recent studies have revealed
      that posttranslational modification of alpha-dystroglycan is associated with
      congenital muscular dystrophy with brain malformations. Since hypoglycosylation
      of alpha-dystroglycan is common amongst several other disorders, a new clinical
      entity called alpha-dystroglycanopathy is proposed. However, only POMGnT1 (MEB)
      and POMT1 (WWS) are shown to have a definite enzymatic activity, and no enzymatic
      activity has been detected in fukutin. We show positive interactions between
      fukutin and POMGnT1. Fukutin may form a protein complex with POMGnT1 and modulate
      POMGnT1's enzymatic activity. Through cDNA microarray, we also show aberrant
      neuromuscular junction formation and delayed muscle fiber maturation in alpha
      dystroglycanopathies, suggesting a new pathomechanism.

PMID- 16447767
TI  - [Collagenopathy (Ullrich congenital muscular dystrophy, Bethlem myopathy)].
AB  - Collagenopathies with collagen VI mutations include Ullrich congenital muscular
      dystrophy (Ullrich's disease) and Bethlem myopathy. Patients with Ullrich's
      disease have generalized muscle weakness, multiple contractures of the proximal
      joints and hyperextensibility of the distal joints. Bethlem myopathy is
      characterized by the combination of proximal muscle weakness and contractures of
      finger, elbow, and ankle joints. We found for the first time a deficiency of
      collagen VI in Ullrich's disease. Furthermore, we found an abnormality of cell
      adhesion and abnormal regeneration or maturation in Ullrich's disease. Mutations
      in the genes COL6A1, COL6A2, COL6A3 are associated with Ullrich's disease and
      Bethlem myopathy. Bethlem myopathy is inherited in an autosomal dominant manner
      and Ullrich's disease usually in an autosomal recessive manner. Recently, de novo
      dominant mutations are reported in Ullrich's disease. We evaluated the role of
      nonsense-mediated mRNA decay (NMD) in Ullrich's disease that has a frameshift
      mutation with a premature termination codon in the COL6A2 gene causing the loss
      of collagen VI. The pharmacological block of NMD caused upregulation of the
      mutant collagen VI and partially functional extracellular matrix formation. Our
      results suggest that NMD inhibitors can be used as a therapeutic tool to rescue
      some human genetic diseases exacerbated by NMD.

PMID- 16447768
TI  - [Mutational and clinical features of Japanese patients with dysferlinopathy
      (Miyoshi myopathy and limb girdle muscular dystrophy type 2B)].
AB  - Mutations in the dysferlin gene cause both Miyoshi myopathy (MM) and limb girdle
      muscular dystrophy 2B (LGMD2B). We examined patients with dysferlinopathy in
      Japan, and identified 28 and 12 different mutations respectively in MM and LGMD2B
      patients. The mean age at onset of the patients with MM was 22 +/- 9 years (range
      12-48 years) and that of the patients with LGMD2B was 26 +/- 10 years (range 11
      43 years). On the average, the first use of a cane was at 33 years (14 years
      after the onset) for MM and 39 years (15 years after onset) for LGMD 2B. Patients
      became wheelchair-bound at 41 years (21 years after onset) in MM and 45 years (21
      years after onset) for LGMD2B. The mean maximum serum CK level at any age of the
      patients was 5,829 +/- 4,273 IU/l (range 1,289-12,566 IU/l ) for MM and 3,787 +/-
      2,493 IU/l (627-10,000 IU/l) for LGMD2B: in both disorders, the serum CK level
      fell in proportion to the duration of the illness. We have identified four common
      four mutations (C1939G, G3370T, 3746delG, and 4870delT) in Japanese patients with
      MM, accounting for 48 percent of all MM mutations in this population. Two of the
      four mutations (G3370T, and 4870delT) accounted for 52 percent of the mutations
      in LGMD2B patients, while the 3746delG mutation was not found in patients with
      LGMD2B. The G3370T mutation may be associated with a milder form of MM and
      LGMD2B. By contrast, the G3510A mutation appears to be associated with a severe
      form of MM.

PMID- 16447769
TI  - [Molecular pathomechanism of distal myopathy with rimmed vacuoles].
AB  - Distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body
      myopathy (HIBM) are genetically identical autosomal recessive muscle disorders
      caused by mutations in the GNE gene. This gene encodes a bifunctional protein
      with UDP-GlcNAc 2-epimerase and ManNAc kinase activities that catalyze the rate
      limiting step and the succeeding step, respectively, in the sialic acid
      biosynthetic pathway. V572L mutation is the most prevalent among Japanese DMRV
      patients and accounts for about 60% of mutant alleles. Clinical spectrum of
      DMRV/HIBM seems to be wider than previously thought in terms of both the severity
      of the disease and the range of affected organs. There are rare asymptomatic
      homozygotes with missense GNE mutations, indicating the presence of mitigating
      factors. Surprisingly, more than 10% of the patients had a variety of cardiac
      abnormalities, suggesting that skeletal muscle may not be the only organ
      involved. Studies on recombinant GNE demonstrate a loss-of-function nature of the
      missense mutations identified. Patients' cells show decreased sialylation status
      which can be recovered by adding GNE metabolites, such as ManNAc and NeuAc. This
      indicates the possibility of developing a therapy for DMRV/HIBM by giving these
      metabolites to patients although we have to await the model mice that are
      currently being produced at several laboratories.

PMID- 16447770
TI  - [MRI diagnosis of neurodegenerative disorders].
AB  - Routine use of high field MRI has greatly contributed to the clinical diagnosis
      of neurodegenerative disorders, because MRI enables to visualize degenerative
      process showing either atrophy of the specific areas or degeneration of specific
      structures. Among many specific MRI signs which have been hitherto proposed to be
      diagnostic for certain neurodegenerative disorders, the author discussed here
      some clinically useful ones with neuropathological interpretations. "Humming-bird
      sign" is highly diagnostic for progressive supranuclear palsy (PSP) because it
      represents focal atrophy of the rostro-dorsal portion of mid-brain tegmentum
      where the neural centers for vertical gaze specifically affected in PSP are
      located. Un-treated Wilson disease patients show frequently "face of giant panda
      sign" of mid-brain which disappears after successful treatment. Although the sign
      is pathognomonic for Wilson disease, neuropathological entity of this MRI
      abnormality has not been known yet. MRI enables to discriminate two types of
      cerebellar atrophies; cerebellipetal atrophy in which ponto-, spino- and olivo
      cerebellar fibers are lost, and cerebellofugal atrophy in which loss of Purkinje
      cells is the main pathological process. In cerebellipetal atrophy, cerebellar
      white matter shows T2 high signal due to the degeneration of nerve fibers in it
      but T2 low signal of dentate nucleus is usually well preserved. This combination
      of degenerative process realized" black teeth sign" of dentate nucleus in MRI. On
      the other hand, cerbellofugal atrophy shows "white teeth sign" of dentate
      nucleus, because the loss of Purkinje cell axons causes signal change of dentate
      nucleus where the axons of Purkinje cells are concentrating. "White teeth sign"
      could also be observed in case of the degeneration of dentate nucleus itself,
      like in DRPLA, but differential diagnosis between Purkinje cell loss and dentate
      degeneration is not so difficult, because the atrophy of the superior cerebellar
      peduncle is detectable in the latter but never seen in the former condition.

PMID- 16447771
TI  - [Diagnostic imaging of spinal diseases].
AB  - With the advent of magnetic resonance imaging, diagnostic accuracy of spinal
      disorders has been much improved regarding their localization and histological
      prediction. The location of herniated disc materials is well appreciated on MR
      images without using contrast materials. MRI can predict the posterior
      longitudinal ligament is perforated or not. Kinematics of the spinal axis and CSF
      flow movement is evaluated on MRI with fast imaging. MR angiography with 3D
      reconstruction depicts the Adamkiewicz's artery and anterior spinal artery.
      Neuritis and neuropathy can be diagnosed by post-contrast T1 weighted image since
      inflammatory nerves are thick and enhance. Some intramedullary deseases tend to
      involve the peripheral area of the spinal cord; others are central. Edema extends
      longitudinally within the spinal cord by sparing the peripheral margin of the
      spinal cord and it is well appreciated with the T2- and proton- weighted images.
      The lateral and posterior funiculi are more frequently involved in multiple
      sclerosis.

PMID- 16447772
TI  - [Perfusion imaging in the diagnosis of acute cerebral infarction].
AB  - There is no doubt that CT and MRI play a major role in the diagnosis and
      selection of optimal therapeutic strategies in cases of acute cerebral
      infarction. However, it is true that there is a wide variation in the scanning
      protocols as well as data analysis procedures; these differences in imaging
      studies could translate into a lack of control over therapeutic strategies,
      thereby undermining the quality of clinical practice. It is obvious that
      standardization of imaging procedures is mandatory; however, so far, no such
      project has been conducted either at home or abroad. With this background, a
      couple of multi-institutional working groups dedicated to the standardization and
      development of practical guideline for imaging procedures in the setting of acute
      cerebral stroke, are now in operation in Japan.

PMID- 16447773
TI  - [Diagnostic imaging on inflammatory lesions of central nervous system].
AB  - Inflammatory lesions of the central nervous system are divided into infectious
      and non-infectious diseases. Diagnostic imaging has important roles for
      understanding the status of diseases, determining the treatment strategy, and
      assessing the effect of the treatment. This article illustrates diagnostic
      imaging modalities useful for evaluating inflammatory lesions of the central
      nervous system and diagnostic strategy which are valuable for differentiating the
      inflammatory lesions.

PMID- 16447774
TI  - [Pathogenesis and treatment of CIDP].
AB  - CIDP is an autoimmune peripheral polyneuropathy. Clinical and electrophysiologic
      features indicate its heterogeneity, and such wide spectrum of the phenotype
      makes difficult to clarify complete pathogenesis. IVIg is an effective therapy no
      less than corticosteroids and plasmaphresis, and getting as the first choice for
      CIDP treatment due to the easy administration and less side effect. However, we
      have noticed that there is certain amount of non-responder, and this therapeutic
      heterogeneity could correspond to independent pathogenesis. In our previous
      report, axonal dysfunction, such as muscle atrophy and decreased CMAPs, is a
      significant factor to represent non-responder. Not only about therapy
      responsiveness, but aspect of long-term prognosis, subjects that show unfavorable
      prognosis indicate significant muscle atrophy and loss of myelinated fibres.
      Hence, decreased axonal function in peripheral nerve should critically affect
      CIDP pathogenesis. In practice, clinician should select proper treatment modality
      in light of clinical symptoms and appropriate medical costs, and if each one does
      not show enough efficacies, another should be admitted because responder for each
      modality is not necessarily overlapped. Although immunosuppressive agents might
      be admitted for non-responder to any other modalities, large randomized control
      trial is not done yet.

PMID- 16447775
TI  - [Perspective for the treatment of diabetic neuropathy: translation from molecular
      studies to bedside].
AB  - Drastic increase in a population of diabetic patients urges to establish
      effective treatment or management of peripheral neuropathy, the most common
      complication of diabetes. Recent studies emphasize the occurrence of peripheral
      neuropathy in patients with impaired glucose tolerance, which condition is now
      shown to augment polyol pathway as well as non-enzymatic protein glycation in the
      peripheral nerve, exerted by postprandial hyperglycemia. Such metabolic cascades
      in turn result in tissue-specific alterations of cellular signaling, represented
      by decreased protein kinase C (PKC) activity and Na, K-ATPase activity in the
      peripheral nerve and contrariwise increased PKC activity in microvessels. The
      decrease in nerve PKC activity was demonstrated to associate with reduced
      membrane alpha-isoform expression and the increase in vessel PKC activity was due
      to membrane beta-isoform expression, respectively. Dual mechanisms of nerve and
      vascular alterations in addition to multiple metabolic factors may operate in the
      development of diabetic neuropathy in a complicated manner. Consequently,
      inhibition of hyperglycemia as well as specific intervention of single molecules
      related to altered cellular signaling is the essential approach for the primary
      prevention of diabetic neuropathy.

PMID- 16447776
TI  - [New therapeutic approaches for familial amyloidotic polyneuropathy].

PMID- 16447777
TI  - [RNAi and neurological disease].
AB  - In many of autosomal dominant diseases such as familial amyotrophic lateral
      sclerosis (ALS) with Cu/Zn superoxide dismutase (SOD1) mutation, a missense point
      mutation may induce the disease by its gain of adverse property. Similar 'gain of
      toxic function' of mutant protein is predicted to cause cell death in other
      autosomal dominant neurodegenerative diseases such as familial Alzheimer disease,
      prion disease, polyglutamine diseases and Parkinson disease. In all these
      familial diseases, one rational approach to therapy is to develop a method to
      specifically eliminate the aberrant protein. Duplex of 21-nt RNA, known as siRNA,
      has recently emerged as a powerful tool to silence gene. Mutant-allele specific
      gene silencing with siRNA was showed in familial ALS and Machado-Joseph diseases.
      We made the transgenic (Tg) mouse of modified small interfering RNA (siRNA). By
      crossing this anti-SOD1 siRNA Tg mouse with a SOD1(G93A) Tg mouse as a model for
      ALS, siRNA halted the development of disease by inhibiting mutant G93A SOD1. Our
      results support the feasibility of utilizing siRNA-based gene therapy of
      neurodegenerative diseases of autosomal dominant inheritance.

PMID- 16447779
TI  - [DNA repair and neurodegeneration].
AB  - Early onset ataxia with hypoalbuminemia (AOA1/EAOH) patients begin with ocular
      motor apraxia and cerebellar ataxia in childhood, and then develop axonal
      peripheral neuropathy and hypoalbuminemia. We and others identified 'aprataxin
      (APTX)' as the causative gene for AOA1/EAOH. APTX binds to XRCC1, which is the
      scaffold protein for BER machinery, and has a HIT-motif, which is supposed to
      have hydrolase activity on nucleotide. These properties suggest that APTX acts on
      DNA during single strand DNA break. The 3' -termini of single strand DNA break
      must be hydroxylated to allow DNA polymerase or ligase to repair; however,
      ordinary the 3' termini is modified by phosphate or others. These unsuitable ends
      have to be removed to repair. To investigate whether the APTX works on DNA and
      remove the unsuitable 3' -end, we incubated recombinant human APTX with variable
      oligonucleotide. We show that APTX has bidirectional exonuclease activity and 3'
      phosphatase activity. These results indicate that APTX might modify the
      phosphorylated 3' -end in a single strand DNA break. To date several diseases
      have been identified as caused by an impairment of quality control system of DNA/
      RNA. The impairment of quality control system of DNA/RNA is a new pathway for
      neuronal degeneration.

PMID- 16447778
TI  - [Regulation of the protein degradation pathway by the ubiquitin family: its
      implication in neurodegenerative diseases].
AB  - Growing lines of evidence suggest that the neurodegenerative diseases are tightly
      linked to the ubiquitin and the proteasome pathway (UPP), which plays a pivotal
      role in selective protein degradation in the cells. Genetic mutations in the
      ubiquitin pathway (ie; parkin and Uchll) cause familial Parkinson's disease (PD),
      and sequestration of such UPP enzymes in the inclusion bodies are observed in not
      only sporadic forms of PD but also in other neurodegenerative diseases. These
      evidences place the reduction of UPP as a central mechanism underlying the
      pathogenesis and progression of neurodegenerative diseases linked to inclusion
      body formation. In addition to the UPP, autophagic pathway (AP), which is
      regulated by the ubiquitin-like modifier systems, attracted considerable
      attention as an alternative pathway to clean-up inclusion bodies in the cells.
      This review highlighted the recent progress in our understanding on the
      regulation of UPP and its cooperation with AP for the quality control of the
      proteins and elimination of ubiquitin positive aggregates.

PMID- 16447780
TI  - [Death of motor neurons and molecular change of glutamate receptors in ALS].
AB  - AMPA receptor-mediated neuronal death is initiated by exaggerated Ca2+ influx
      through AMPA receptor channels, and the Ca2+ permeability of the AMPA receptor
      ion channel depends strongly upon the presence or absence in its composition of
      an edited GluR2 subunit whose glutamine (Q) residue is substituted by arginine
      (R) at the Q/R site due to RNA editing. The pivotal role of the RNA editing at
      the GluR2 Q/R site in neuronal death has been clearly demonstrated in animal
      experiments and its deficiency is a direct cause of neuronal death. We
      demonstrated that the editing efficiency at the GluR2 mRNA Q/R site varied
      greatly, from 0% to 100%, among the single motoneurons of each individual with
      ALS, whereas it remained 100% among those of normal controls. In addition, the
      editing efficiency was more than 99% in the cerebellar Purkinje cells of ALS,
      spinocerebellar degeneration and normal control groups. By contrast, there was no
      significant difference as to both the amount and the proportion to total GluRs
      mRNA of GluR2 mRNA between normal and ALS motoneurons. Thus, marked GluR2
      underediting in ALS motoneurons occurs in a disease specific and region selective
      manner, and may be closely relevant to ALS etiology.

PMID- 16447781
TI  - [Death with dignity].

PMID- 16447782
TI  - [Care and problems in intractable neurological diseases--home care of intractable
      diseases from the view of a practicing physician].
AB  - Taking into account how to care patients at home with intractable neurological
      disease and their family, I have introduced the achievement of the medical caring
      technique by an aged family member, the risks of the PEG and acute respiratory
      failures under BiPAP, the problems in home rehabilitation, and the experiences of
      home terminal care, from the view point of a practicing physician. Home caring
      pursues to support patients and their family to live peacefully with disease with
      highest quality of life. Hospice caring is also an important issue. From now on,
      I would like to try to give even better home care by early recognition of
      problems and by cooperating with hospitals, clinics and other field workers.

PMID- 16447783
TI  - [Network to support patients with ALS in the Hyogo prefecture].
AB  - The author reports network to support patients with amyotrophic lateral sclerosis
      in the Hyogo prefecture. Three types of network are working, which are the
      network in the multidisciplinary team in the hospital, the medico-welfare network
      in the area and the network intra-hospitals in the prefecture. We have to
      establish effective network with a passion, a mission and an action.

PMID- 16447784
TI  - [Improvement and evaluation of QOL for the patients with nanbyo, intractable
      diseases].
AB  - The intractable diseases that are nanbyo in Japanese, have been defined by the
      Ministry for establishing the care system. This article argued the key issues
      including narrative based approach, palliative care and SEIQoL-DW for improving
      and evaluating of QOL of the patients with nanbyo.

PMID- 16447785
TI  - [Adenosine deaminase 2 in the diagnosis of tuberculous pleuritis].
AB  - PURPOSE: We examined the usefulness of adenosine deaminase 2 (ADA2) in the
      diagnosis of tuberculous pleuritis. SUBJECTS: A hundred cases, 78 male and 22
      female, with pleural effusion were examined. With regard to pleural effusion, 18
      cases were transudate and 82 cases (9 tuberculous pleuritis, 27 lung cancer, 8
      mesothelioma, 5 malignant diseases except lung cancer and mesothelioma, 5 benign
      asbestos pleurisy, 10 empyema, 10 parapneumonic effusion, one SLE, one parasitic
      infection, and 6 undetermined etiology) were exudates. The last 6 cases with
      unknown origin were excluded in this study. RESULTS: Pleural adenosine deaminase
      (ADA) was 90.4 +/- 22.4 U/l (mean +/- SD) and pleural ADA2 was 80.4 +/- 21.9 U/l
      in tuberculous pleuritis, both were significantly higher than those in non
      tuberculous exudates (p < 0.001). In the diagnosis of tuberculous pleuritis,
      pleural ADA showed 100% sensitivity and 88% specificity, whereas pleural ADA2
      showed 100% sensitivity and 91% specificity. CONCLUSION: Pleural ADA2 is useful
      in the diagnosis of tuberculous pleuritis, which has similar sensitivity and a
      little better specificity compared with pleural ADA.

PMID- 16447786
TI  - [Should chemotherapy for pulmonary tuberculosis be started after the completion
      of pretreatment sputum examination?].
AB  - PURPOSE: Investigation on the influence of early start of chemotherapy on the
      results of sputum smear and culture (Ogawa medium and BACTEC MGIT960). OBJECT AND
      METHOD: Retrospective study for tubercle bacilli positive pulmonary tuberculosis
      cases in our hospital. RESULT: Starting chemotherapy before the completion of
      pretreatment sputum examination was found to have no adverse effect on smear
      positive rate and smear positive grade (246 cases), culture contamination rate on
      Ogawa medium and BACTEC MGIT960 (1128 sputums), culture positive rate and culture
      positive grade/time to confirm positive on Ogawa medium (245 cases), and culture
      positive rate on BACTEC MGIT960 (239 cases). Time to confirm positive on BACTEC
      MGIT960 was slightly, but significantly prolonged (1.16 days delay in cases with
      1-3 days chemotherapy [228 cases], and 4.01 days delay in cases with 4-6 days
      chemotherapy [59 cases]). CONCLUSION: Unfluence of early start of chemotherapy on
      the results of sputum smear and culture is minor. In most of bacilli positive
      pulmonary tuberculosis cases chemotherapy can be started before the completion of
      pretreatment sputum examination.

PMID- 16447787
TI  - [A survey on nosocomial tuberculosis infection control in hospitals in Osaka
      City].
AB  - PURPOSE: To ascertain nosocomial tuberculosis (TB) infection control practice in
      hospitals in Osaka City. METHOD: A questionnaire was distributed in the
      orientation meeting and collected at the occasion of medical inspection in all
      196 hospitals in Osaka City in 2003. RESULTS: TB patients were diagnosed in about
      half of hospitals in the past 3 years. Basic TB infection control measures were
      taken in the majority of hospitals; such as chest X-ray screening for all
      inpatients, health check for employees, tuberculin skin test (TST) for newly
      employed staff, and nomination of a person in charge of TB infection control.
      Control measures were practiced more often in hospitals where TB patients were
      diagnosed, such as "fiberoptic bronchoscopy is to be conducted last in the
      working hours to avoid contamination of TB bacilli in a room," "TST (including
      two-step method) for all newly employed staff," "Staff wear N95 mask when they
      deal with TB patients/suspects," and the differences were statistically
      significant. DISCUSSION: It is necessary in hospitals in Osaka City to strengthen
      nosocomial TB infection control as TB patients were diagnosed in about half of
      hospitals in the past 3 years. Low cost infection control measures were
      undertaken more often among hospitals where TB patients were diagnosed.
      Introduction of high cost equipment or improvement of facilities should be
      considered in hospitals of high TB risk. Guidelines formulated based on analysis
      of the survey should facilitate all hospitals to introduce at least low cost
      effective tuberculosis infection control measures.

PMID- 16447788
TI  - [A 2-month-old male with intractable epileptic seizures].

PMID- 16447790
TI  - [Relationships between spinal deformities and respiratory function in patients
      with severe motor and intellectual disabilities syndrome].
AB  - The term severe motor and intellectual disabilities syndrome (SMIDS) refers to
      describe a heterogeneous group of disorders with severe physical disabilities and
      profound mental retardation. Many patients with SMIDS have spinal deformities
      such as spinal rotation and scoliosis. On the other hand, they often have
      respiratory dysfunction, resulting in high mortality from respiratory failure.
      Therefore, we hypothesized that spinal abnormalities might affect respiratory
      dysfunction, and analyzed the correlation between spinal abnormalities (Cobb
      angles (CA) and spinal rotation scores (SRS)) and respiratory parameters
      (observed during tidal breathing at static supine posture) in 10 patients with
      SMIDS (M: F 2:8, age 29.0 +/- 7.3 years). The patients inability to make effort
      in spirometry prevented us from evaluating vital capacity and forced expiratory
      volume. We measured respiratory rate, tidal volume, and expiratory gas during
      tidal breathing for 10 minutes. There was no patient with the athethotic type of
      CP. CA and SRS were found to be correlated with each other (r = 0.81, p < 0.01).
      CA was inversely correlated with tidal volume (both Vt and Vt/Height;r = -0.69, p
      < 0.05). Both CA and SRS correlated with respiratory rate (r = 0.67 and 0.69,
      respectively). Moreover, the slope of the regression lines of the VO2-VCO2 plots
      (V-slope) was correlated with CA (r = 0.86, p < 0.01). Contrary to our
      expectation, none of the respiratory parameters showed significant correlations
      with BMI. Moreover, we found no relationship between the spinal deformity (CA or
      SRS) and BMI. These observations suggest that the spinal abnormalities affect
      respiratory patterns in a restrictive manner and increase the respiratory change
      rate during tidal breathing in patients with SMIDS.

PMID- 16447789
TI  - [Etiology and management of neonatal seizures--successful treatment by
      midazolam].
AB  - Etiology and management of neonatal seizures was retrospectively studied in 39
      patients, who were admitted in our neonatal intensive care unit. Midazolam was
      administered to 22 patients by intravenous bolus injection (0.15 +/- 0.08 mg/kg)
      and/or continuous intravenous infusion (0.33 mg +/- 0.11 mg/kg/hr), both of which
      were judged as effective in 71% and 76% of the patients, respectively. Seven
      patients showed decrease of blood pressure possibly related with administration
      of midazolam, but five of them were managed by decreasing dose of the drug or
      observation of clinical pictures. We consider that midazolam is effective and
      relatively safe for the management of neonatal seizures.

PMID- 16447791
TI  - [Setting up of a day group service system for severely disabled children, the
      "Koala Club"].
AB  - This is a report of the setting up of a day group service system for severely
      disabled children, the "Koala Club". The "Koala Club" was started in 1993, and
      has been running outside of the hospital since 1997. A support group for the
      "Koala Club" was established in 1999. Currently 13 children attend the "Koala
      Club". The staff of the "Koala Club" consists of one coordinater, four nurses and
      eight care workers. The medical care is fulfilled by nurses. The "Koala Club"
      open two days a week. It has been supervised by a doctor and a case worker. There
      is an important role for physicians in the regional care of disabled children.

PMID- 16447792
TI  - [Clinical characteristics and pharmacotherapy of extremely disruptive behavior
      disorders in people with mental retardation].
AB  - People with mental retardation often have behavioral problems. Psychotropic
      medications are used for the treatment of extremely disruptive behavior disorders
      in many cases. We surveyed the clinical characteristics and the current status of
      the pharmacotherapy regimens for inpatients with severe intellectual disabilities
      and behavior disorders at 8 national psychiatric hospitals. Many of them were men
      between 20 and 40 years and more than half of them had both extremely mental
      retardation and high motor ability. Antipsychotic drugs and anticonvulsants were
      frequently used. As they had more severe behavior disorder, they were taken the
      more psychotropic drugs. Autism was significantly associated and rough behavior
      was apparently associated with higher doses. A very weak correlation between the
      total score of extremely disruptive behavior disorders and the number of
      psychotropic drugs being administered per patient was seen. Use of new medicines,
      such as atypical antipsychotic drugs, was found about fifteen percent of the
      cases. In order to establish useful pharmacotherapy regimens for people with
      severe mental retardation and behavior disorders, it is necessary to perform
      routine judgment and evaluation of the pharmacotherapy focusing on targeted
      symptoms. We should also be attention to the quality of life issue. The aim of
      medical treatment should not be care workers' convenience, but be the improvement
      of quality of life of patients.

PMID- 16447793
TI  - [Magnetic resonance imaging of the brain in phenylketonuria].
AB  - To investigate the correlation between the abnormalities of magnetic resonance
      imaging (MRI) of the brain and blood phenylalanine (Phe) levels in
      phenylketonuria (PKU) and hyperphenylalaninemia (HPA), we reviewed MRIs from 16
      patients with early treated PKU and HPA. Their ages ranged from 4-24 years and
      were found by mass screening and treated from early infancy, and 5 patients with
      late detected PKU who were aged 24-33 years. The former patients had no
      remarkable neurological signs or symptoms. One patient of the latter had severe
      mental retardation and 3 patients had mild to border mental retardation. Axial T1
      weighted and T2-weighted spin echo sequences, fluid attenuated inversion recovery
      MR sequences (FLAIR) through the brain were performed. The scans were graded
      according to the extent of increased signal intensity of white matter on T2
      weighted and FLAIR sequences. To investigate the influence of plasma Phe levels,
      three approaches were used. Firstly an average of all yearly serial blood Phe
      concentration was calculated for each patient, then Phe was determined for a
      period of 6 months and 12 months prior to MRI, and also for their lifetime up to
      their age at the time this study began. These average blood Phe levels were
      classified into four categories: group A:Phe level below 5 mg/dl, group B:5-8
      mg/dl, group C:9-12 mg/dl, group D:above 12 mg/dl. MRI findings were not
      significant in group A. Remarkable high signals of white matter were obtained in
      group C and D, except for one patient in group D whose MRI finding was normal.
      MRI findings correlated to long-term dietary control stronger than those of 6
      months prior to MRI. The clinical significance of MRI abnormalities is still
      unclear, and further study is required to clarify the relationship of the MRI
      findings and clinical conditions.

PMID- 16447794
TI  - [Treatment of sleep apnea syndrome in a Down syndrome patient with behavioral
      problems by noninvasive positive pressure ventilation: a successful case report].
AB  - The use of noninvasive positive pressure ventilation (NPPV) is increasingly
      accepted as a treatment of respiratory problems in patients with neuromuscular
      disease. However, its use in mentally retarded and un-cooperative patients has
      not been reported. We report here the evaluation and treatment of sleep apnea in
      a Down syndrome patient. After recovering from a life threatening respiratory
      failure the patient had persistent sleep apnea syndrome. Limited examinations
      disclosed that he had two types of apnea; obstructive and central type apnea. Our
      treatment was a diet with intake restricted up to 1,000 kcal per day for the
      obstructive apnea, and NPPV with low dosage of oxygen for the obstructive and
      central apnea. With these treatments in one year's hospitalization, his quality
      of life was significantly improved. He has continued the treatment in the
      outpatient department and enjoys a better quality of life both at home and in the
      community. The successful treatment of this case may become an example of the
      more extensive use of NPPV for such respiratory problems in handicapped children
      and adults with behavioral problems.

PMID- 16447795
TI  - [Pleural effusion associated with long-term dantrolene administration in three
      patients with severe motor and intellectual disabilities].
AB  - Chronic unilateral pleural effusion developed in three patients with severe motor
      and intellectual disabilities. All patients received 5-15 years of dantrolene
      administration for their spasticity. The cause of pleural effusion was
      indistinct, despite close investigations for etiologies such as infection or
      tumor. The pleural fluid consisted of sterile exudate in all patients. One
      patient had eosinophilia in his pleural fluid, while peripheral blood
      eosinophilia was seen in the other two. The pleural biopsy and autopsy specimens
      revealed only non-specific inflammatory findings. After dantrolene therapy was
      discontinued, pleural effusion almost disappeared in two patients in the
      following several months, but the other died of multi-organ failure from another
      underlying disease. It is important to take chemical pleurisy into consideration
      when dealing with pleural effusion of unknown etiology. Moreover, respiratory
      side effect should be examined in patients treated with chronic dantrolene
      administration.

PMID- 16447796
TI  - [Child case of chronic inflammatory demyelinating polyneuropathy showing
      phagocytic myelinolysis and regenerative changes on electron microscopic analysis
      of the sural nerve].
AB  - We reported a 9-year-old boy with chronic inflammatory demyelinating
      polyneuropathy (CIDP) showing characteristic electron microscopic study findings
      on a sural nerve biopsy. He came to our hospital because of muscle weakness
      progressing slowly for 2 years. He developed distal muscle weakness and
      areflexia. Cerebrospinal fluid protein was elevated without pleocytosis. Moter
      conduction velocities were reduced. Partial conduction block and abnormal
      temporal dispersion were present. The electron microscopic findings on a sural
      nerve biopsy comprised both active demyelinating lesions, i.e., macrophages were
      peeling away the myelin lamellae and phagocytosing some myelin debris, and
      remyelinating lesions with onion bulb formations. Some findings mimic electron
      microscopic changes in Guillain-Barre syndrome, although tests for the known anti
      ganglioside antibodies were negative. So, he was diagnosed as having definite
      CIDP and prednisolone with gamma-globulin infusion was effective to ameliorate
      his symptoms.

PMID- 16447797
TI  - [Case of Sanfilippo syndrome type B and Wilson disease born to unrelated
      parents].
AB  - A 5-year-old boy visited a hospital because of macrocephalus, mental retardation
      and hepatic dysfunction, and was suspected to have Wilson's disease since his
      father had this disease. The serum level of ceruloplasmin was low, but urinary
      copper excretion was not increased markedly. He was treated with D-penicillamine.
      He was then reffered to our hospital because of his facial features suggesting
      mucopolysaccharidosis. Based on mucopolysacchariduria and the deficiency of N
      acetylglucosaminidase, the diagnosis of Sanfilippo syndrome type B was made.
      Molecular analyses identified him as a compound heterozygote for both the ATP7B
      (A844V/2659delG) and alpha-N-acetylglucosaminidase (V241M/R482W) genes,
      responsible for Wilson's disease and Sanfilippo syndrome type B, respectively.
      Although born to non-consanguineous parents, he had two rare autosomal recessive
      diseases. In this case, liver dysfunction was attributed to Wilson's disease, and
      mental retardation to Sanfilippo syndrome.

PMID- 16447798
TI  - [New strategy for the treatment of multiple myeloma].

PMID- 16447799
TI  - [Histopathological findings of pulmonary complications in 16 patients who
      received allogeneic hematopoietic stem cell transplants].
AB  - Pulmonary complications are frequent and sometimes lethal in allogeneic
      hematopoietic stem cell transplantation recipients. In our hospital, 16
      transplanted patients had pulmonary complications at post-mortem examination. We
      review the patients' clinical courses and histopathological findings of their
      lungs, and discuss the factors related to the onset of the pulmonary
      complications. In 16 patients, 10 had infectious lung diseases and the other 6
      were non-infectious. Five of the patients with infectious diseases had fungal
      infections: 2 aspergillosis, 2 candidiasis and 1 mucormycosis. In the other 5, 2
      had cytomegalovirus pneumonia, 1 had herpes simplex virus pneumonia and 2 had
      bacterial pneumonia. These ten patients were highly immunocompromised because of
      steroid therapy or neutropenia. The histopathological diagnosis of all 6 patients
      with non-infectious disease was diffuse alveolar damage (DAD). Most of the DAD
      patients were also complicated with other organ damage due to regimen-related
      toxicity (RRT), and their respiratory symptoms had appeared during the rapid
      tapering off of their immunosuppressant drugs. These results revealed that
      prevention of fungal infection was still important for highly immunocompromised
      patients. Efforts to reduce RRT such as using a reduced intensity regimen and
      careful tapering off of immunosupressants are expected to lead to a decrease in
      non-infectious pulmonary complications.

PMID- 16447800
TI  - [Clinical course of the disease and the level of WT1 mRNA in 191 patients with
      acute myeloid leukemia (AML): joint research by 23 institutions in Japan].
AB  - We evaluated the clinical course of acute myeloid leukemia (AML) and the levels
      of WT1 mRNA in 191 AML patients. Of 114 previously untreated patients with AML,
      107 cases were positive for WT1 mRNA (93.9% : 107/114). WT1 mRNA expression
      levels declined to below 50 copies/microg RNA ("negative") after remission was
      achieved in all 66 patients who achieved remission and 84.8% (47/54) cases were
      "negative" at the end of the follow-up periods. On the other hand, WT1 mRNA was
      expressed in 87.0% of non-remission cases (47/54), maintaining 50 copies/microg
      of RNA or higher ("positive"). In all 29 cases who relapsed during the follow-up
      observation period after achieving remission, WT1 mRNA levels declined
      transiently approximately around the time of achieving remission and then rose
      again when the disease relapsed. Moreover, we determined the time of elevation of
      WT1 mRNA in 29 relapsed cases. In 79.3% of relapsed cases (23/29), WT1 mRNA
      levels rose above 200 copies/microg RNA, 43 days (median) before the diagnosis of
      "relapse". Given the percent of the correct diagnosis, WT1 mRNA at 200
      copies/microg RNA appeared to be a reasonable cut-off level for early detection
      of AML-relapse. The WT1 mRNA level reflected the clinical condition. Taken
      together, these findings indicate that WT1 mRNA levels allow us to detect the
      presence of so-called "minimal residual disease" (leukemic cells) that cannot be
      detected by morphological examination. Besides these promising data, this kit is
      suitable for routine monitoring of AML because this kit utilizes peripheral blood
      as a test specimen, reducing the patient's burden at the time of collection of
      clinical samples as compared with bone marrow aspirate.

PMID- 16447801
TI  - [Second transplant from the same donor without conditioning for bone marrow
      aplasia after non-myeloablative hematopoietic stem cell transplantation for
      chronic myeloid leukemia].
AB  - We describe a 56-year-old woman with chronic myeloid leukemia (CML) and a past
      history of stroke, who underwent nonmyeloablative hematopoietic stem cell
      transplantation (NST) with conditioning consisting of fludarabine and
      cyclophosphamide. The regimen related toxicity was minimal and patient did not
      require transfusions of any blood products nor did she have any infections after
      the NST Since mixed chimerism was observed in both lymphocytes (70% were donor
      type) and granulocytes (none were donor type) at 56 days after NST, donor
      lymphocyte infusion (DLI) was performed on day 68 and then immunosuppressant
      therapy was discontinued. DLI resulted in graft versus leukemia (GVL) effect,
      causing pancytopenia and bone marrow aplasia. A second hematopoietic stem cell
      transplantation was performed without conditioning on day 157, and complete donor
      type hematopoiesis and molecular remission of CML were achieved. Although
      engraftment of donor hematopoietic stem cells was not obtained after the first
      transplantation, donor lymphocytes were engrafted by nonmyeloablative
      conditioning and immunosuppression. That is, the same result might have been
      achieved even if the patient had received transfusion of only donor lymphocyte
      subsets in the first step. Based on this case report, a potential cell therapy is
      proposed composed of the preceding donor lymphocyte infusion alone, which induces
      GVL effects, and subsequent donor hematopoietic stem cell transplantation.

PMID- 16447803
TI  - HealthSouth responds. Company sues Scrushyfor return of bonuses.

PMID- 16447802
TI  - [Close correlations between CD20 expression, a small mature plasma cell
      morphology and t(11 ; 14) in multiple myeloma].
AB  - Stratification of patients with multiple myeloma (MM) may be important. We
      investigated 138 MM patients, focusing on correlations between CD20 expression,
      11 ; 14 translocation, morphology of MM cells, cyclin D1 immunostaining, and the
      prognosis. About 15% of patients (7/47cases) were CD20-positive, small mature MM
      cells, with positive cyclin D1 in the nucleus and 11; 14 translocation. Two color
      analysis of CD38 x CD20 antigens may be necessary to investigate CD20 expression
      on MM cells. Rituximab may be effective for the treatment of CD20-positive MM.

PMID- 16447804
TI  - New chapter in NCFE saga. SEC's civil fraud charges against executives at failed
      firm offer cold comfort for the hospitals, physicians hurt by the debacle.
AB  - Trouble revisited National Century Financial Enterprises last month, when the
      Securities and Exchange Commission sued four former execs for the accounting
      fraud that caused the financial firm's collapse in 2002. The investigation
      worries some, but others, like Kathy Patrick, left, an attorney representing
      former NCFE investors, says there is "legitimate business to be done in the
      purchase of healthcare receivables."

PMID- 16447805
TI  - Ten indictments in IT scandal. Feds accuse former Medical Manager execs of fraud.

PMID- 16447806
TI  - Medicare muddle. Rx drug benefit confuses both enrollees, provider.

PMID- 16447807
TI  - Medicare, Medicaid anxiety. Providers wait for word on cuts, reimbursements.

PMID- 16447808
TI  - Behind the FTC's lawsuit. Payers pointed finger at Evanston Northwestern.

PMID- 16447809
TI  - UnitedHealth pays the price. $9.2 billion insurers' merger not without
      concessions.

PMID- 16447810
TI  - Wrestling with conflicts. Cleveland Clinic, devicemaker ties raise concerns.

PMID- 16447811
TI  - Alvarado case stretches on. Deliberations must restart after juror is kicked out.

PMID- 16447813
TI  - Who'll be celebrating? New year looks promising for many, including merger-ready
      hospitals and managed care, but challenges are coming on just as strong.

PMID- 16447812
TI  - Rebuilding in New Orleans. One hospital struggles with more indigent care,
      staffing shortages.

PMID- 16447814
TI  - By the numbers. Top 20 pharmaceutical companies, ranked by U.S. sales, October
      2004 to September 2005.

PMID- 16447815
TI  - [Prevalence of common mental disorders in Italy, risk factors, health status, and
      utilization of health services: the ESEMeD-WMH project].

PMID- 16447816
TI  - Aneuploidy, centrosome alteration and securin overexpression as features of
      pituitary somatotroph and lactotroph adenomas.
AB  - OBJECTIVE: To verify the presence of numerical chromosomal aberrations (NCAs) in
      different types of pituitary adenomas (PAs) and to investigate 2 of the
      mechanisms that are possibly related to aneuploidies in PAs: securin
      overexpression and centrosome alterations. STUDY DESIGN: Twenty-one PAs of
      different types were analyzed with interphase fluorescence in situ hybridization
      (FISH) on paraffin sections with centromeric probes for chromosomes 2, 3, 8, 11
      and 12. In all cases, the immunohistochemical expression of securin was evaluated
      and the number of cells with abnormal nuclear shape recorded. The ultrastructural
      study of centrosomes was performed in a subset of 12 tumors. RESULTS: At
      interphase FISH analysis, growth hormone (GH)-cell and prolactin (PRL)-cell PAs
      showed multiple chromosome gains and a low frequency of chromosome losses,
      suggesting a hyperdiploid chromosome assessment. In contrast, in the other types
      of PAs a lower frequency of NCAs was observed. In addition, when compared to
      other types of PAs, GH-cell and PRL-cell adenomas showed overexpression of
      securin and a higher number of both cells with abnormal nuclear shape and cells
      with centrosomes. CONCLUSION: Somatotroph and lactotroph adenomas are
      characterized by aneuploidy, abnormal nuclear shape and centrosome amplification,
      which are possibly related to securin overexpression.

PMID- 16447817
TI  - Malignancy associated changes in epithelial cells of buccal mucosa: a potential
      cancer detection test.
AB  - OBJECTIVE: To analyze the presence of malignancy associated changes (MACs) in
      normal buccal mucosa cells of lung and breast cancer patients and their
      relationship to tumor subtype, stage and size. STUDY DESIGN: Buccal mucosa smears
      of 107 lung cancer and 100 breast cancer patients and corresponding healthy
      subjects were collected, stained by the DNA-specific Feulgen-thionin method and
      scanned using an automated high-resolution cytometer. Nuclear texture features of
      a minimum of 500 nuclei per slide were calculated, and statistical classifiers
      using Gaussian models of class-probability distribution were designed, trained
      and tested in 3 parts: (1) ability to separate cancer patient samples from
      controls, (2) cross-validation of classifiers for different cancer types, and (3)
      correlation of MAC expression with tumor subtype, stage and size. RESULTS: Lung
      and breast cancer induce MACs in normal buccal mucosa cells. The classifiers
      based on the selected nuclear features correctly recognized >80% of lung and
      breast cancer cases. The results indicate that MAC detection is not dependent on
      the tumor subtype, stage or size. CONCLUSION: The presence of MACs in buccal
      mucosa cells offers the potential for developing a new noninvasive cancer
      screening test.

PMID- 16447818
TI  - Proteomic analysis of protein expression in prostate cancer.
AB  - OBJECTIVE: To investigate protein expression in prostate cancer using 2
      dimensional gel electrophoresis (2-DE) and mass spectrometry. STUDY DESIGN: Cells
      were collected from 29 peripheral zone tumors and from benign tissue by scraping
      cut surfaces of radical prostatectomy specimens. Samples were suspended in a
      medium with protease inhibitors and prepared for 2-DE. Gels were analyzed, and
      protein spots that differed quantitatively between tumor and benign tissue were
      identified via mass spectrometric fingerprinting of tryptic fragments and tandem
      mass spectrometry sequence analysis. RESULTS: In total, 63 spots differed between
      cancer and benign samples (p < 0.01); 56 were overexpressed (> 1.5 fold) in
      cancer and 7 underexpressed (< 0.6 fold). Among overexpressed proteins were
      transcription factors (nucleoside diphosphate kinase 1) and enzymes involved in
      gene silencing (chromobox protein), protein synthesis (39S ribosomal protein L12,
      BiP protein, protein disulfide isomerase), degradation (cytosol aminopeptidase,
      endopeptidase Clp, inorganic pyrophosphatase) and energy metabolism (acyl-CoA
      dehydrogenase, isocitrate dehydrogenase, NADH-ubiquinone oxidoreductase, pyruvate
      dehydrogenase), heat-shock proteins (60 and 70 kd), structural proteins
      (cytokeratins) and membrane proteins (stomatinlike protein 2). CONCLUSION: The
      protein profile of prostate cancer differs from that of benign tissue. Several
      potential target proteins for detection or evaluation of prognosis in prostate
      cancer were identified.

PMID- 16447819
TI  - Cytomorphologic and morphometric limitations of the assessment of atypia in
      fibroadenoma of the breast.
AB  - OBJECTIVE: To investigate the relevance of nuclear morphometry in separating the
      categories of "fibroadenoma" and "fibroadenoma with atypia." STUDY DESIGN: Thirty
      consecutive breast lumps, on which a fine needle aspiration (FNA) diagnosis of
      fibroadenoma was followed by excision and histopathologic confirmation of the
      diagnosis, were included. Atypia on cytology was based on cell overlap, nuclear
      enlargement and cell dyscohesion. Nuclear morphometric comparison was carried out
      between the categories of fibroadenoma, fibroadenoma with atypia and grade 1
      ductal carcinoma cases that formed part of an earlier study. The parameters
      employed were area, roundness, diameter, perimeter and grey level. RESULTS: Among
      the 30 cases of fibroadenoma reported on FNA, an additional component of atypia
      was noted in 5. On subsequent histopathology, atypia was not confirmed in any of
      the cases. On morphometric analysis, a significant difference was noted between
      fibroadenoma and fibroadenoma with atypia categories, as between fibroadenoma and
      grade 1 ductal carcinoma cases. However, no significant difference was noted
      between fibroadenoma with atypia and grade 1 ductal carcinoma cases. CONCLUSION:
      FNA assessment of atypia in cases of fibroadenoma is difficult. Even conventional
      nuclear morphometry, though supporting the initial impression of atypia, does not
      help with this assessment. Also, based on morphometry alone, there may be
      difficulty separating fibroadenomas with atypia and grade 1 ductal carcinomas.
      Larger studies, employing other morphometric parameters, such as chromatin
      texture and fractal dimension, may shed further light on the subject.

PMID- 16447820
TI  - Dilution effect of nontumor cells on flow cytometric DNA S-phase fraction in
      breast cancer fine needle aspirates.
AB  - OBJECTIVE: To analyze the proportion of nontumor cells in fine needle aspirates
      of breast carcinoma and its influence on flow cytometric S-phase fraction (SPF)
      estimation. STUDY DESIGN: We analyzed the proportion of nontumor cells in fine
      needle aspiration biopsy smears, performed flow cytometric analysis of DNA ploidy
      and SPF on freshly aspirated tumor material and analyzed histograms manually and
      automatically using Multi-Cycle AV software (Phoenix Flow Systems, San Diego,
      California, U.S.A.) for cell cycle analysis. We corrected SPF of diploid tumors
      for the dilution effect using an individually established percentage of nontumor
      cells (individual correction) and the mean proportion of nontumor cells in
      diploid tumors (factor correction). RESULTS: The proportion of nontumor cells
      ranged from 0.5% to 76.6% (mean, 12.6; SD, 15.7) in 55 diploid tumors and from
      0.5% to 53% (mean, 8.6; SD, 8.9) in 84 aneuploid tumors (p=0.178). In 14 of 139
      (10%) samples, the proportion of nontumor cells exceeded 20%. The mean SPF values
      of diploid tumors without correction were 4.9% (manually) and 6.5%
      (automatically) and of aneuploid tumors, 9.5% and 11.0%, respectively. In
      univariate Cox survival analysis, noncorrected SPF was a significant prognostic
      factor in overall survival (p < 0.001). Neither individual nor factor correction
      of SPF significantly changed its prognostic value. CONCLUSION: Fine needle
      aspirates contain low proportions of nontumor cells, having an insignificant
      dilution effect on SPF estimation. Most probably, SPF could be reliably estimated
      usingfreshly aspirated tumor material without any correction or adjustment.

PMID- 16447821
TI  - Basic principles and applications of fractal geometry in pathology: a review.
AB  - The basic principles and prospects of fractal geometry in pathology are
      promising. All articles found with a PubMed search with the keywords fractal
      dimension (FD) and related to pathology were reviewed. All fractal objects have
      FDs, commonly calculated with box counting. Fractal geometry has been applied to
      measure the irregularities of nuclear and glandular margins to distinguish
      malignant lesions from benign ones, to measure the infiltrative margin of a
      malignant tumor, to assess tumor angiogenesis and to measure the distribution of
      collagen in tissue. Fractal geometry has also been applied to assess the
      irregular distribution of chromatin in malignant cells. Biologic model formation
      is possible with fractal geometry. In the future, fractal geometry may help with
      the diagnosis, understanding of pathogenesis and management of lesions. It may
      also provide new insights into disease processes.

PMID- 16447822
TI  - Segmentation of microscopic images of small intestinal glands with directional 2
      D filters.
AB  - We present an image segmentation algorithm for small intestinal glands consisting
      of goblet cells that are evenly distributed and arranged in parallel at the base.
      Making use of the properties of the chain distribution of the goblet cells,
      directional 2-dimensional (2-D) linear filters with different orientations were
      designed to enhance the rims of the intestinal glands. Segmentations are based on
      the combined responses of the multiple zero-phase directional 2-D linear filters.
      For comparisons, outputs of combined directional filters are shown along with
      those of the comparable nondirectional Gaussian filters. Segmentation results of
      small intestinal glands of both normal and cancer cases are provided.

PMID- 16447823
TI  - Ownership of clinical practice.

PMID- 16447824
TI  - Bariatrics and sensitivity.

PMID- 16447825
TI  - Multiple-chemical sensitivity.
AB  - Multiple-chemical sensitivity (MCS) is a condition in which individuals have an
      acute hypersensitivity to low levels of chemicals found in everyday substances,
      such as household cleaning agents, pesticides, fresh paint, new carpeting,
      synthetic building materials, newsprint, perfume, and numerous other
      petrochemical products. This condition continues to remain somewhat of a mystery
      to the medical community, and its true prevalence rate is unknown because many
      cases are not identified and reported as MCS. This article will inform the reader
      about the condition of MCS.

PMID- 16447826
TI  - Opioid tolerance: a perioperative nursing challenge.
AB  - Opioid analgesia is used more frequently in patients with chronic pain
      unresponsive to non-opioid therapy. The result is a growing number of individuals
      admitted to the hospital for acute pain (trauma or surgery) who are opioid
      tolerant. Nursing strategies to improve pain intervention in this population are
      discussed.

PMID- 16447827
TI  - Gastrointestinal tract.

PMID- 16447828
TI  - Administer single-site 30-mL intramuscular injection?
AB  - A physician orders fosphenytoin to be administered intramuscularly in a dosage of
      30 mL in volume. A change in the traditional practice of limiting intramuscular
      injection volumes to 5 mL in adult patients is discussed.

PMID- 16447830
TI  - Changing nursing practice through a nursing journal club.
AB  - As hospitals seek to promote evidence-based nursing practice and improve the
      quality of bedside nursing care, formation of a nursing journal club can be one
      strategy to accomplish both goals.

PMID- 16447829
TI  - Graduate students' perceptions of online teaching and relationship to preferred
      learning styles.
AB  - As the nursing faculty shortage continues, the online format is being used more
      frequently for delivery of graduate nursing courses. Its effect on students'
      learning and their perceptions of online teaching needs to be investigated. This
      descriptive study examines the students' learning styles; their perceptions of
      six online nurse educator courses, the faculty, and the asynchronous format; and
      their overall perceptions of online teaching and learning.

PMID- 16447831
TI  - Politics in the workplace.

PMID- 16447832
TI  - On nursing, moral autonomy, and moral responsibility.

PMID- 16447833
TI  - Registered Nurse Safe Staffing Act of 2005: Part II.

PMID- 16447834
TI  - Osteoporosis: what women want to know.

PMID- 16447835
TI  - Phase III and IV clinical trials: what you and your patients need to know.

PMID- 16447836
TI  - On leadership. Signature strenghths: achieving your destiny.
AB  - All of us have signature strengths that make us unique and valuable. There are
      talents we were born with and the ones we have perfected over the years. If these
      are utilized well it will allow us to live out our inborn destiny. The good news
      about nursing is that there are many very different kinds of positions where one
      can find a niche that fits her signature strengths. Without a match, we will live
      our lives as a sundial in the shade. Where there is a match, we will live as we
      were born to live, as sundials in the sun, creating value for those around us.
      Our task is to find that sunlight for ourselves and our staff and to position all
      of us to work in the light of our signature strengths.

PMID- 16447837
TI  - Want to improve your investigation results?

PMID- 16447838
TI  - Portable air cleaners.

PMID- 16447839
TI  - Domo Arigato, Mr. Roboto!

PMID- 16447840
TI  - 'Mission control' model taking hold.

PMID- 16447841
TI  - Creative training.

PMID- 16447842
TI  - A new safety credential is born.

PMID- 16447843
TI  - The right PPE for disaster responders.

PMID- 16447844
TI  - CrVI: new regulations and detection methods.

PMID- 16447846
TI  - End the hodgepodge strategy.

PMID- 16447845
TI  - Beyond putting out fires.

PMID- 16447847
TI  - Using feedback as a leadership practice.

PMID- 16447848
TI  - Expanding the menu.

PMID- 16447849
TI  - Deeply prepared.

PMID- 16447850
TI  - Does increasing breathing resistance increase respirator faceseal leakage?

PMID- 16447851
TI  - The value of comprehensive geriatric assessment.
AB  - Comprehensive geriatric assessment (CGA) provides guidance in planning care for
      elderly patients. The goals of CGA include reduction of health care cost, early
      recognition and treatment of geriatric syndromes and improved survival and
      quality of life for patients. Evidence from randomized controlled studies has
      identified the value of CGA and some of its limitations. Studies of CGA in
      institutional settings and in home care provide the basis for specific
      interventions to targeted groups of high-risk patients. Strategies for fall
      prevention, appropriate use of pharmacotherapy, and prevention of in-hospital
      delirium have grown out of the application of this multidisciplinary tool. Future
      research focused on a more precise definition of the potential financial benefits
      of CGA may facilitate the task of communicating its value to decision makers.

PMID- 16447852
TI  - More care at home: the challenge of creating viable community alternatives to
      nursing home care.
AB  - Creating a national long-term care (LTC) delivery "infrastructure"--one that
      would make home-based care more accessible to people with extensive needs--will
      be a major undertaking. It will require new service organizations that have the
      authority to provide and coordinate an appropriate array of services. Medicaid
      Managed Long-Term Care (MLTC) and the Programs of All-Inclusive Care for the
      Elderly (PACE) offer two promising examples of what the service organizations of
      the future might look like. The history of how these plans developed illuminates
      challenges that others will encounter. Further expansion of these types of
      organizations requires resolution of resource, staffing, and operational issues.

PMID- 16447853
TI  - Victimization of the elderly homeless.
AB  - Using data from the National Survey of Homeless Assistance Providers and Clients
      (NSHAPC), this article examines the applicability of Felson's Routine Activities
      Theory to a national probability sample of older homeless individuals. Results
      indicate that the relative protection that women often have from most crimes is
      not transferred to the older homeless woman who is more likely than her male
      counterparts to be the victim of sexual assault but equally as likely to be the
      victim of theft and physical assault. Likewise, the protection often noted
      afforded by age against victimization is also not seen among the homeless. The
      research demonstrates that being male and having mental and physical health
      problems as well as substance abuse problems increases the likelihood of
      victimizations among the homeless population, in general When predictors of
      victimization were considered for the 50 and older sample, these predictors
      remained the same except that the gender remained significant only for sexual
      assault. These findings are consistent with and supportive of utilizing Felson's
      Routine Activities Theory to understand and explain victimization among the older
      homeless population.

PMID- 16447854
TI  - Caring for the dying: from a "negative" to a "positive" legal right to die at
      home.
AB  - The choice of the old and terminally ill to die at home has been the subject of
      various types of research. However, one of the aspects of this subject, which has
      been investigated very little, is its legal context. The absence of such legal
      research is contrasted by the vast amount of academic writing on the legal
      aspects of the right to die with dignity and euthanasia. The object of this
      article is to analyze and break down the "right to die at home" into its
      different legal components. This legal analysis will be based on Professor Isaiah
      Berlin's definition of two different concepts of liberty: negative and positive
      freedoms. The main conclusion from the legal analysis presented in this article
      is that it is important to understand that at the legal level the right to die at
      home is dependent on many different elements. These elements may be classed in
      two basic categories: negative and positive freedoms and rights. Even though the
      former is a necessary condition of the latter, without the latter the first
      remains purely theoretical for many old people.

PMID- 16447855
TI  - Forcing isolation: Medicare's "in the home" coverage standard for wheelchairs.
AB  - Older adults and people with physical disabilities can get Medicare coverage for
      mobility devices, like wheelchairs, walkers, and scooters, which are necessary
      for use in their homes. However they cannot get coverage for mobility devices
      that are solely for functioning outside their home. Since the institution of
      Medicare's coverage standards for mobility devices, and other kinds of durable
      medical equipment, nearly four decades ago, advances have been made in three
      critical areas: improvements in design of mobility devices that allow people to
      participate more fully in their communities; widespread societal recognition that
      with appropriate accommodations many limitations on functioning can and should be
      lifted; and recent court decisions requiring that individuals with disabilities
      be provided with the necessary supports to live as independently as possible in
      their communities. The current interpretation of Medicare's coverage standards
      for mobility devices does not reflect these advances. The Centers for Medicare
      and Medicaid Services' (CMS) interpretation of Medicare's coverage standard
      prevents people from getting needed medical equipment to function within their
      communities. By contemporary medical and legal standards, the [CMS's]
      interpretation is unreasonable and quite likely unlawful. The Medicare statute
      neither specifies that durable medical equipment is exclusively for use in the
      patient's home nor bars consideration of an equipment's use outside the home.
      There is no indication of Congressional intent to support this limitation of
      coverage. CMS has both the authority and the responsibility to interpret the
      Medicare statute so as to be consistent with historical developments in law,
      technology and social mores. United States Supreme Court precedent holds that
      agencies are "charged with the administration of [a] statute in light of everyday
      realities." Everyday realities have changed since Medicare was launched in 1965.
      Laws such as the Rehabilitation Act of 1973, the Americans with Disabilities Act
      of 1990 and the Ticket to Work and Work Improvements Incentives Act of 1999
      reflect a broad, bipartisan commitment to increasing community integration of
      people with disabilities. This commitment is evident in judicial decisions,
      including Olmstead v. L.C. ex rel. Zimring, and executive orders, such as
      President George W. Bush's New Freedom Initiative, a set of proposals to promote
      opportunities for Americans with disabilities to learn and develop skills, engage
      in productive work, make choices about their daily lives, and participate fully
      in their communities. Developing political and legal standards are consistent
      with medical opinion: the costs of isolation for people with disabilities can
      include poorer health outcomes and higher systematic health costs. Also,
      scientific evidence indicates that people who get inappropriate mobility devices
      given their needs develop secondary medical conditions. In light of technological
      advances that today make appropriate equipment available and community
      integration possible, CMS has a responsibility to update its interpretation of
      the Medicare statute. While CMS must rightly be concerned with costs associated
      with a more modern interpretation of Medicare's coverage policy, other insurers
      have found that an appropriate standard has not led to an explosion in the
      provision of more expensive mobility devices. Specifically, the brief recommends
      that the Centers for Medicare and Medicaid Services: (1) correct its Medicare
      coverage policy to cover medically appropriate mobility devices that help
      maintain or improve functioning for people in the environments they are likely to
      encounter in their daily routines (both inside and outside of the home), and (2)
      guard against unnecessary expenses for Medicare by incorporating mandatory
      equipment evaluations to ensure that people receive equipment that matches their
      needs. While durable medical equipment encompasses a wide array of assistive
      devices, this brief will focus on wheeled mobility items, recognizing that this
      analysis will have varying applications to other durable medical equipment as
      well.

PMID- 16447856
TI  - Commentary on the special issue on the cognitively impaired elderly (volume 22,
      number 4).

PMID- 16447857
TI  - Doctors in the cross hairs.

PMID- 16447858
TI  - It's the new walking. Scooters evolve from medical need to lifestyle choice.

PMID- 16447859
TI  - Bringing up baby.

PMID- 16447860
TI  - Dr. Frank Miranda: the music of dentistry. Interview.

PMID- 16447861
TI  - Avoiding mediation review.

PMID- 16447862
TI  - New law: Family Wealth Preservation Trust enhanced!

PMID- 16447863
TI  - Oral pathology case. Peripheral giant cell granuloma.

PMID- 16447864
TI  - [Study on biomass dynamic changes of Codnopsis pilosula under the planting
      density and fertilizing amount].
AB  - Study on the biomass dynamic changes of Codnopsis pilosula (Franch.) Naff. under
      the different planting density and fertilizing amount of the four levels
      respectively via the random methods have showed out: the best combination for the
      stems and leaves are 1.05 million plant/hm2 and 240 kg fertilizer/hm2. Its
      biomass accumulation can achieve 652 mg/d; That for the root are 0.6 million
      plant/hm2 and 240 kg fertilizer/hm2 and the weight of every fresh root achieved
      14. 88g. The results will be helpful to cultivating and fertilizing of Codnopsis
      pilosula.

PMID- 16447865
TI  - [Study on model of heat and mass transfer in Dioscorea opposita with microwave
      drying technique].
AB  - A new mathematical model, aimed at investigating the behaviors of microwave
      drying of traditional chinese medicine was established. It based on mass-energy
      consersvation law. Dioscorea opposita Thunb. was used as sample and its drying
      efficiency have been developed at different levels of microwave power and sample
      thickness. The results shown that the levels of them have a strong influence on
      drying process. The experimental values were approximately in accord with the
      calculated values by mathematical model. It explained successfully the behaviors
      of microwave drying of Diosorea opposita Thunb. slices.

PMID- 16447866
TI  - [Study on chemical constituents from stem of Mallotus apelta].
AB  - Eight compounds were isolated from the ethyl-acetate extract of the stem of
      Mallotus apelta Muell. -Arg. The structures of eight compounds were identified by
      means of spectroscopic analysis as 12-ursen-3-one (I), 3-hydroxy-12-ursen (II),
      mussaenoside (III), 6-methoxy-2H-1-benzopyron4-one (IV), ursolic acid (V), acetyl
      aleuritolic acid (VI), beta-sitosterol-3-O-beta-D-glucopyranoside (daucosterol
      VII), beta-sitosterol (VII). Compound I to approximately V were obtained from
      this plant for the first time.

PMID- 16447867
TI  - [Study on chemical constituents of Lagotis yunnanensis].
AB  - OBJECTIVE: To study the chemical constituents of Lagotis yunnanensis W. W. Smith.
      METHODS: Compounds were isolated from the ethanolic extract of the title herb by
      silicagel column chromatography and polyamide column chromatography, and their
      structures were identified by physical and chemical evidences and spectral
      methods. RESULTS: Six compounds were isolated and identified as quercetin-3-O
      beta-D-glucoside (1), apigenin-7-methyl ether (2), E-cinnamic acid (3), Z
      cinnamic acid (4), E-p-coumatic acid (5), Z-p-coumatic acid (6). CONCLUSION: All
      the compounds are isolated from this plant for the first time.

PMID- 16447868
TI  - [Purification and analysis of polysaccharides from the caudex of Undaria
      pinnatifida].
AB  - To isolate polysaccharides with hot water from the caudex of Undaria pinnatifida,
      and precipitate with ethanol. The protein in polysaccharides was removed by
      sevage way. DEAE-52 and Sephadex G-200 column chromatography were used to isolate
      and purification polysaccharides, three purified polysaccharides F2, F3 and F4
      were obtained. It was identified that they were homogeneity. The ultraviolet
      spectrum showed there was no proteins and nucleic acids in F2, F3 and F4. Through
      thin-layer chromatography analysis, F2, F3 and F4 were mainly composed of Gal,
      Fuc, Man and Glu acid. F2 also contained Glu and Rha.

PMID- 16447869
TI  - [Identification of 5 constituents of the aqueous extract of Isatis indigotica by
      HPLC-MS2].
AB  - OBJECTIVE: To identify five constituents in the aqueous extract of Isatis
      indigotica Fort. METHODS: After separation of the aqueous extract of Isatis
      indigotica Fort. by HPLC, the eluates of five peaks were collected separatively
      and analysed by MS2. UV spectra and MS2 were compared with those of reference
      standards of cytidine, uridine, guanosine xanthine and hypoxanthine. RESULTS:
      Each HPLC elute of the aqueous extract had same retention time, UV spectra and
      fragment pattern in the MS2 spectrum as the corresponding standards. CONCLUSION:
      Five constituents of the aqueous extract of Isatis indigotica Fort. are
      identified as cytidine, hypoxanthine, uridine, xanthine and guanosine.

PMID- 16447870
TI  - [The main pharmacology study of ZhongSheng capsule dosage form changing].
AB  - OBJECTIVE: To study pharmacological action variety of ZhongSheng Pill dosage form
      changing from pill to capsule. METHODS: Using anti-pathogenic microbe,
      antipyretic and antipyrotic effect as the pharmacological index,we compared the
      pharmacological action between Zhongsheng Pill formation and Capsule formation.
      RESULTS: Zhongsheng Capsule had various degrees extraneous antagonistic actions
      against familiar and conditioned pathogenic bacteria and virus of respiratory
      tract. Furthermore it coud also reduce the death ratio of mouse infected by
      staphylococcus aureus and influenza virus, remove fever and diminish
      inflammation. All these effects had the dose-effect relationship. There were no
      difference between pill fromation and cpasule formation. CONCLUSION: Zhongsheng
      Capsule retain the original pharmacological action of Zhongsheng Pill after
      dosage form changing.

PMID- 16447871
TI  - [Study on effect of Astragalus membranaceus injection on hematopoiesis in anemic
      mice with myelosuppression].
AB  - OBJECTIVE: To investigate the effect of AMI on hematopoiesis in anemic mice and
      explore the possible mechanisms. METHODS: Anemic mice model resulted from
      myelosuppression by irradiation and cytotoxic chemotherapeutic compounds were
      randomly divided into three groups: treated group I, treated group II and anemic
      control group. Intraperitoneal doses of AMI(500 mg/kg, 1000 mg/kg) were given to
      the treated group, and equal doses of physiological saline were given to the
      anemic control group. On 7 days after treatment, the count of whole blood cells
      and bone marrow cells were determined by blood auto-analyzer. The numbers of CFU
      GM (granulocyte and macrophage colony forming unit), CFU-E (colony forming unit
      erythroid), BFU-E (burst forming unit-erythroid), CFU-Meg(colony forming unit
      megakaryocyte) were determined by using technique of hematopoietic progenitor
      cells culture in vitro. Expression of anti-apoptosis protein BcL-XL and BcL-2 in
      BMC were determined by immunohistochemistry. RESULTS: RBC, HB, PLT (P < 0.05) and
      BMC (P < 0.01) in treated group I were significantly higher than that of anemic
      control. The number of CFU-E, BFU-E and CFU-Meg as well as expression of anti
      apoptosis protein BcL-XL of BMC in treated group I also were significantly higher
      than that of anemic control (P <0. 05 or P <0. 01), while numbers of CFU-E as
      well as expression of anti-apoptosis protenin BcL-XL of BMC in treated group II
      were higher than that of anemic control (P < 0.05). CONCLUSION: AMI can lesson
      apoptosis of bone marrow cells and promote hematopoietic progenitor cells to
      differentiate along the erythroid and megakaryocytoid line by up-regulating
      expression of antiapoptosis protein BcL-XL of BMC.

PMID- 16447872
TI  - [Study on effects of salidroside on lipid peroxidation on oxidative stress in rat
      hepatic stellate cells].
AB  - OBJECTIVE: To investigate the effect of antioxidant Salidroside on the lipid
      peroxidation of oxidative stress in rat hepatic stellate cells in vitro. METHODS:
      HSC-T6 were incubated with 0.1 mM ferric nitrilotriacetate complex (FeNTA). MTT
      colorimetry was used for assaying proliferation of HSC. Cytotoxicity was measured
      by LDH colorimetry. Collagen type I accummulation in the culture media was
      measured by ELISA. Intracellular MDA, SOD, GSH and GSH-PX levels in the culture
      media were measured by their reagent boxes. RESULTS: HSC incubation with FeNTA
      resulted in a significant production of intracellular MDA and GSH, associated
      with decreasing SOD and GSH-PX activity. Exposure of HSC to FeNTA significantly
      enhanced the number of proliferating HSC and collagen type I levels in the
      culture medium. All these effects were reversed by the antioxidant Salidroside.
      CONCLUSION: The mechanism of Salidroside on fibrosis may be related to inhibit
      lipid peroxidation.

PMID- 16447873
TI  - [Study on the antipyretic, analgesic effects of qingkailing freeze-dried powder
      for injection and its antipyretic mechanism].
AB  - OBJECTIVE: To investigate the antipyretic, analgesic effects of Qingkailing
      Freeze-Dried Powder for Injection (QI) and its mechanism of the antipyretic
      effect. METHODS: The rabbit model of 2, 4-dinitrophenol-induced fever and the rat
      model of endotoxin-induced fever were established and the body temperatures were
      observed. Radioimmunoassay was adopted to detect the levels of IL-1beta and cAMP
      in the hypothalamus of rats. The analgesic effects were tested by hot-plate and
      writhing reaction method. RESULTS: QI showed marked antipyretic effects on the
      2,4-dinitrophenol-induced fever and the endotoxin-induced fever. At the same
      time, QI remarkably decreased the contents of IL-beta and cAMP in the
      hypothalamus. QI also remarkably reduced the frequency of acetic acid-induced
      writhing and delaied the time of licking rear feet. CONCLUSION: QI has
      antipyretic, analgesic effects. Its mechanism of the antipyretic effects on rats
      may be inhibiting the production of IL-1beta and accordingly decreasing cAMP in
      the hypothalamus.

PMID- 16447874
TI  - [Effects of parthenolide on the activity and expression of urokinase type
      plasminogen activator in PGCL3 cells].
AB  - OBJECTIVE: To study the effect of Parthenolide on the activity and expression of
      urokinase type plasminogen activator (uPA) on PGCL3 cells and to investigate the
      antitumor mechanisms of Parthenolide. METHODS: MTT assay was used to determine
      the growth inhibition by Parthenolide in PGCL3 cells; Effect of Parthenolide on
      the activity of uPA secreted by PGCL3 cells was measured by chromogenic substrate
      assay;The expression level of uPA protein was assessed by Western blot analysis.
      RESULTS: Parthenolide could inhibit proliferation of PGCL3 cells after 24h
      treatment, the IC50 value was 17.60 micromol/L; Parthenolide reduced
      significantly the activity of uPA secreted by PGCL3 cells and down-regulated the
      expression level of uPA protein. CONCLUSION: The antitumor activity of
      Parthenolide is involved in the activity and expression of urokinase type
      plasminogen activator.

PMID- 16447875
TI  - [Experimental study of the effect of Bushen Huoxue recipe on biological
      characters of osteoblasts in vitro].
AB  - OBJECTIVE: To observe the effect of Bushen Huoxue Recipe on cell proliferation,
      differentiation, maturation and mineralization in rats cultured osteoblasts.
      METHODS: Osteoblasts from craniums of newly born SD rats were cultured in vitro.
      MTT, PNPP and ARS were used to observe the proliferation, activity of ALP and the
      number of mineral node of cultured osteoblasts in vitro. RESULTS: It was found
      that Bushen Huoxue Recipe had the effect on stimulating cell proliferation,
      activity of ALP and the number of mineral node of cultured osteoblasts (P < 0.01
      or P < 0.05). CONCLUSION: Bushen Huoxue Recipe can promote proliferation,
      differentiation, maturation and mineralization of the osteoblasts cultured in
      vitro.

PMID- 16447876
TI  - [Effects of Yiqimingmu solutions on electroretinogram in rats with retinal
      photochemical damage].
AB  - OBJECTIVE: To observe the effect of the Yiqimingmu solutions on electroretinogram
      of rats with retinal photochemical damage. METHODS: Twenty-four SD rats were
      divided into four groups randomly: control group, model group, low dose group,
      high dose group. All groups except the control one were continually exposed to
      green fluoresent light with an level of 1900 +/- 106.9 Lux for 24 hours,which was
      used to establish rats retinal photochemical damage model. Different doses of
      Yiqimingmu solutions were respectively irrigated into rats 7 days before light
      expose in low dose and high dose group. Saline solutions instead was used in
      control and model group. At 6 hours and 6,14 days after light exposed, change of
      electroretinogram a wave and b wave was observed. RESULTS: It was suggested that
      the difference of the average amplitude of ERG a wave and b wave was not
      significant between left eyes and right eyes in the control group. The average
      amplitude of ERG a wave and b wave decreased continually at the 6th hour and 6th
      day and uncovered at the 14th day after light exposed in the model group. In the
      low dose and high dose group, Yiqimingmu solutions had protective effect on
      lowing ERG a wave after rats retinal photochemical damage. CONCLUSION: Yiqimingmu
      solutions has protective effect on rats retinal photochemical damage.

PMID- 16447877
TI  - [Influence of super fine crushing on the extraction of polysaccharides from
      polystictus versicolor].
AB  - OBJECTIVE: To study the extractive technique of Polysaccharides from Polystictus
      Versicolor pretreated by super fine crushing. METHODS: Polystictus versicolor was
      pretreated by technique of super fine crushing, and the contrast examination of
      super powder (5 microm) and polystictus versicolor was done. Then the extractive
      technique of polysaccharides from polystictus versicolor super powder was
      optimized by the orthogonal design. RESULTS: The extraction yield of
      Polysaccharides from polystictus versicolor super powder was higher 61% than that
      of polystictus versicolor. The optimum extractive technique of polysaccharides
      was 100 degrees C, 80 min and extracting 3 times. CONCLUSION: Technique of super
      fine crushing is propitious to the extraction of polysaccharides from polystictus
      versicolor.

PMID- 16447878
TI  - [Study on extraction methods of volatile oil from Mosla soochowensis].
AB  - OBJECTIVE: To study the different extraction methods of the volatile oil from
      Mosla soochowensis Matsuda and to determine the optimum extraction method.
      METHODS: The yields and the chemical constituents of volatile oil were used to
      compare the different extraction methods including SFE-CO2, steam distillation
      and organic solvent (petroleum ether) extraction. RESULTS: The yield of volatile
      oil by means of SFE-CO2 was 3.46%, which was higher than others. The quality of
      the oil by means of SFE-CO2 and steam distillation was better. Based on the
      result of GC-MS, the constituents of volatile oil were similar. It was mainly the
      methyleugenol, accounted for about 42%. The second was monocyclic terpene, such
      as bornene, dihydrocarvon, carvacrol, accounted for about 27%. The third was
      sesqutierpenoids, such as nerolidene etc, accounted for about 19%. CONCLUSION:
      SFEE-CO2 is the optimum extraction method of the volatile oil from Mosla
      soochowensis Matsuda.

PMID- 16447879
TI  - [Clinical study on treatment of cirrhosis by different dosages of salvia
      injection].
AB  - OBJECTIVE: To find the optimal dosage of salvia injection (SI) on treating
      cirrhosis with hepatitis B virus (HBV). METHODS: 120 patients, whose diagnosis
      was confirmed as cirrhosis with HBV and differentiated by TCM typing as blood
      stasis blocking collaterals type, were divide into two groups. one was
      compensatory cirrhosis group (A group, 60 patients), another was decompensated
      cirrhosis group (B group, 60 patients). In each group, patients were selected and
      randomly divided by lottery method into the large (24 ml), middle (16 ml) and
      small dose (8 ml) of SI treated groups and control group. The primary treatment
      was same in all patients. The course of treatment was 60 days. The clinical
      symptoms and signs, and liver functional indexes as ALT and TBil, and liver
      fibrosis indexesas procollagen type III (PCIII), collagen type IV (CIV) and
      hyaluronic acid (HA), were measured before and after treatment. RESULTS:
      Different dosages of SI all could improve the clinical symptoms and decline the
      level of ALT, TBil, PC III, CIV and HA (P < 0. 05). Treatment of large dosages SI
      showed the best efficacy, superior to that of middle and small dosage of SI (P <
      0.05), but no significant difference was found between the efficacy of the latter
      two (P > 0.05). The efficacy of SI to compensatory cirrhosis group was better
      than that of decompensated cirrhosis group (P < 0.05). CONCLUSION: The large
      dosage (24 ml) of SI have the best effect to treat the cirrhosis with BHV,
      particularly to patients with compensated cirrhosis.

PMID- 16447880
TI  - [Effect of Shenqi Fuzheng injection (SFI) on immune function in patients with
      congestive heart failure].
AB  - OBJECTIVE: To study the effect of Shenqi Fuzheng injection on the humoral
      immunity (IgG IgM IgA), cellular immunity (T-lymphocyte subsets), Superoxide
      dismutase (SOD). Lpo and Plasma viscosity in the patients with congestive heart
      failure (CHF). METHODS: Sixty patients with CHF, whose heart function belonged to
      NYHA grade II-IV were randomly divide into two groups. The treaded group were
      treated with SFI 100 ml, and the control group were treated by nitroglycerine in
      jection 10 mg, the drug were administered respectively by adding in 5% glucose
      solution 500 ml for intravenous dripping, once a day, 20 days as one therapeutic
      course. Venous blood from cubital vein was collected before and after treatment
      to detect the IgG, IgM, IgA, T-lymphocyte subsets, SOD, LPO and Plasma viscosity.
      RESULTS: The clinical heart function markedly improved rate and total effective
      rate in the treated group was singificantly better than those in the control
      group respectively (P < 0.05). the left ventricular ejecting frection (LVEF) and
      end syctolic volume (ESV) were improved in both group (P < 0.05, P < 0.01), and
      the improvement in the treated group was superior to that in the control group (P
      < 0.05). In the treated group after treatment, the CD4, SOD level and CD4/DC8
      ratio increased (P < 0.05), level of LPO, IgG and IgM lowered (P < 0.05)
      significantly, while those in the control group were not changed singificantly (P
      > 0.05). Plasma viscosity of treatment group also got better improved than before
      (P < 0.05), and there was a significantly difference between the two groups after
      treatment (P < 0.05). CONCLUSION: SFI Can improve the immune funtion of CHF
      patients, and can be taken as an importmant auxiliary treatment for CHF.

PMID- 16447881
TI  - Preparing the population for a healthier old age.

PMID- 16447882
TI  - Recent developments in cystic fibrosis.

PMID- 16447883
TI  - Nutrition for the lads.
AB  - Throughout their lives, men's health compares badly to that of women. This
      article looks at healthy eating for men, whose energy and nutritional
      requirements differ from women's. It outlines the changes in food and alcohol
      intake that some males need to make in order to reduce their risk of ill-health
      and disease. A healthy diet in adolescence is also important as this is the
      period of rapid growth when much of the body's bone mass is laid down. Since men
      attend health centres and visit their general practitioners less often than
      women, health professionals should consider raising nutritional issues
      opportunistically.

PMID- 16447884
TI  - Twins and more--2. Practical aspects of parenting in the early years.
AB  - Caring for twin, triplets or more can be a daunting prospect for parents, however
      much the children are wanted and loved. Multiple birth babies are more likely to
      be born preterm and of low birth weight, adding to the practical, financial and
      emotional pressures of coping with two or more babies. Good preparation and
      advice before the babies are born, as described in Part 1 of this article
      (Journal of Family Health Care 2005; 15151: 143-146) is essential. After the
      birth, parents need continuing support and access to care from professionals who
      understand their different and special needs. Bereavement counselling and support
      may also be required, as the mortality rate is higher for multiple births. Part
      Two looks at the care commonly needed for multiple birth families during the
      first five years.

PMID- 16447885
TI  - Partnerships in health: are they working? CPHVA Annual Professional Conference
      2005.

PMID- 16447886
TI  - MPs on PCT reform: 'clumsy, incoherent and ill-judged'.

PMID- 16447887
TI  - Clincal supplies. A market in unmentionables in need of 'modernisation'.

PMID- 16447888
TI  - Data briefing. Choice and travel.

PMID- 16447889
TI  - Patient choice. Harness the power of information.

PMID- 16447890
TI  - On a neglected condition.

PMID- 16447892
TI  - NHS finances. The winter of discontent: chief execs tell their story.

PMID- 16447891
TI  - Hewitt: struggling trusts to get management reinforcements.

PMID- 16447893
TI  - On uncertainty around PFI.

PMID- 16447894
TI  - Hewitt: go Deutsch to shift work out of hospitals. Interview by Daniel Martin.

PMID- 16447895
TI  - Barometer. Mental health Dec 2005.

PMID- 16447896
TI  - Primary care. Community service.

PMID- 16447897
TI  - On primary care.

PMID- 16447898
TI  - The ten commandments of oral implantology.

PMID- 16447899
TI  - A 16-year study of the microgap between 272 human titanium implants and their
      abutments.
AB  - A microgap has been described at the level of the implant-abutment connection.
      This microgap can be colonized by bacteria, and this fact could have relevance on
      the remodeling of the peri-implant crestal bone and on the long-term health of
      the peri-implant tissues. The authors report on 272 implants with screw- or
      cement-retained abutments retrieved from humans for different causes during a 16
      year period. In the implants with screw-retained abutments, a 60-microm microgap
      was present at the level of implant-abutment connection. In some areas the
      titanium had sheared off from the surface and from the internal threads. The
      contact between the threads of the implant and those of the abutment was limited
      to a few areas. Bacteria were often present in the microgaps between implant and
      abutment and in the internal portion of the implants. In implants with cement
      retained abutments, a 40-microm microgap was found at the level of the implant
      abutment connection. No mechanical damage was observed at the level of the
      implant or of the abutment. All the internal voids were always completely filled
      by the cement. No bacteria were observed in the internal portion of the implants
      or at the level of the microgap. The differences in the size of the microgap
      between the two groups were statistically significant (P < .05). In conclusion,
      in screw-retained abutments the microgap can be a critical factor for
      colonization of bacteria, whereas in cement-retained abutments all the internal
      spaces were filled by cement. In these retrieved implants, the size of the
      microgap was markedly variable and much larger than that observed in vitro.

PMID- 16447900
TI  - Crestal bone loss minimized when following the crestal preparation protocol: a
      histomorphometric study in dogs.
AB  - Initial breakdown of the implant-tissue interface generally begins at the crestal
      region in successfully osseointegrated implants. The purpose of this study was to
      evaluate the effect on crestal bone loss (CBL) around implants specially
      developed for immediate loading with a unique crestal drill. After 8 weeks
      postextraction, 6 young male mongrel dogs received 48 implants (XiVE) in the
      region corresponding to the 4 mandibular premolars. The implant sites were
      prepared according to the manufacturer's protocol with conventional standard
      drills. Before implant placement, the crestal drill was used in the experimental
      group but not in the control group. After a healing period of 12 weeks, the dogs
      were sedated and euthanized. Through linear measurements, from the top of the
      implant to the first bone-implant contact, the amount of CBL was determined. The
      histomorphometric results of CBL (mean +/- SEM) were 0.88 +/- 0.13 mm (range 0.0
      3.0 mm) in the experimental group and 1.69 +/- 0.17 mm (range 0.0-4.2 mm) in the
      control group. The difference was statistically significant (P < .05) when the
      implants were used as the experimental units. The statistical analysis also
      revealed significance when the dogs were used as the experimental units (P <
      .05). When the median was used for analyses, the CBL was 0.44 mm for the
      experimental group and 1.91 mm for the control group. Crestal bone loss was
      minimized when the crestal preparation protocol was carefully followed by using
      the osseocondensating XiVE implant system.

PMID- 16447901
TI  - Three-year analysis of Tapered Screw-Vent implants placed into extraction sockets
      grafted with mineralized bone allograft.
AB  - With clinicians placing more dental implants, it is becoming increasingly
      important to maintain bone volume after tooth extraction. This article reports
      the results of implants placed into extraction sites grafted with particulate
      mineralized bone allograft (Puros). A total of 313 extraction sites were grafted
      with mineralized bone graft during a 36-month period. A total of 252 Tapered
      Screw-Vent dental implants were placed into the grafted extraction sites after a
      4- to 7-month healing period. All reentries revealed a bony hard structure
      acceptable for osteotomy preparation. A total of 244 of these implants have been
      restored with fixed prosthesis and 6 with removable overdentures for a total of
      250 loaded implants. A total of 6 implants failed, which required their removal
      (2 implants before load and 4 after loading), resulting in a 97.6% implant
      success rate. We conclude that mineralized human allograft placed into extraction
      sites is clinically useful to maintain bone volume. This material provided a bony
      hard structure acceptable for implant placement with good success rates.

PMID- 16447902
TI  - The use of laser-welded titanium framework technology: a case report for the
      totally edentulous patient.
AB  - Laser-welded technology has become a viable alternative to the conventional lost
      wax-casting technique in the field of implant dentistry. Studies have
      demonstrated the predictable nature of laser-welded titanium frameworks for
      endosseous implants in the partial and totally edentulous patient. A standardized
      impression and fabrication procedure is required for an accurate and predictable
      superstructure. More long-term studies are needed for more widespread acceptance
      and usage by dental practitioners.

PMID- 16447903
TI  - House mental classification system of denture patients: the contribution of Milus
      M House.
AB  - Although Dr Milus M. House is credited with devising a method to describe the
      mental classification of complete denture patients, a review of the literature
      raises questions regarding the origin of the system. Dr Ewell Neil should have
      received credit for developing the classification system attributed to Dr House.
      The contribution of Dr House appears to be a detailed expansion of the
      classification and the subsequent popularization of the system.

PMID- 16447904
TI  - New method of sedation in oral surgery.
AB  - Local anesthesia, the well-known method of sedation, usually is insufficient for
      dental implantation and the augmentation of the alveolar ridge, because the
      operations last for 1 to 2 hours and patients may experience fear and strain.
      This article examines a new complex sedation method using ketorolac, midazolam,
      and a local anesthetic 4% solution of articaine hydrochloride and epinephrine
      (Septanest) in combination with a vasoconstrictor. This method was applied to 67
      patients operated on for dental implantation with screw implants or for the
      alveolar ridge augmentation with biocompatible materials. The control group,
      which consisted of 20 patients, received local anesthesia with articaine
      epinephrine only. Most of the control patients were found to have experienced
      fear and strain during the aforementioned surgical procedures; their blood
      pressure and pulse rate increased, and more than half of them experienced pain.
      No disorders of hemodynamics or the psychoemotional status of the patients were
      observed during sedation with ketorolac, midazolam, and articaine-epinephrine.
      Furthermore, anterograde amnesia was determined for the 80% of the patients in
      the test group.

PMID- 16447905
TI  - The effect of a biphasic ceramic on calvarial bone regeneration in rats.
AB  - Bioactive ceramics (calcium phosphate ceramics, hydroxyapatite ceramics) are now
      extensively used in oral surgery. The purpose of this study was to assess the
      effect of a new biphasic ceramic (Ceraform) on the osteogenesis in a rat
      calvarial defect model. Fifteen Wistar rats were used in this study. Two
      symmetrical 3-mm wide defects were created in the skull of each rat. The left
      defect was left empty as a control and the right defect was filled with the
      ceramic. The rats were sacrificed at day 30, and the calvarial specimens were
      processed for qualitative and quantitative histological examinations. The
      material exhibited no adverse effects, but no bone healing was noted either. No
      statistical difference regarding bone regeneration was observed between the 2
      defects (P > .05). This study showed that Ceraform did not elicit any
      inflammatory reaction; however, it had no effect on bone regeneration, and this
      material seems suitable only as a space-maintaining material.

PMID- 16447906
TI  - Development of the anterior chordal canal.
AB  - Resent advances have led to the reexamination of the intraosseous pathway of the
      chorda tympani a few years ago and they stated that the nerve never enters the
      mandibular fossa and its exit the skull base in the sphenopetrosal fissure. In
      our report, 58 temporal bones were investigated after maceration and formalin
      fixation in order to understand the development of the anterior chordal canal.
      Our study revealed that the chorda tympani leaves the tympanic cavity through the
      tympanosquamosal fissure before formation of the anterior chordal canal of
      Huguier. This canal is situated parallel to and in front of the musculotubal
      canal and formed by the processus inferior tegminis tympani and the sphenoid bone
      between the second and fifth years of age. Prior to the age of 2, only the exit
      of the bony canal exists which is gradually followed by the appearance of a
      groove in the growing processus inferior tegminis tympani. The borders of the
      groove elevate and develop to upper and lower plates which lengthen with similar
      plates of the sphenoid bone, completing the anterior chordal canal by the fifth
      postnatal year. The entrance of the canal develops above the petrotympanic
      fissure and similar to the canal itself, it is also completely formed in the
      fifth year. In case of an incomplete development the anterior chordal canal
      remains partially opened laterally which might allow the head of the mandibula to
      effect the chorda tympani mechanically causing Costen's syndrome.

PMID- 16447907
TI  - A case of nonrotation of the midgut with a middle mesenteric artery.
AB  - In 2002, we came across a very rare case of nonrotation of the midgut with a
      middle mesenteric artery (MM) (tentative name). It was found in a 73-year-old
      Japanese female cadaver donated for student dissection at Kumamoto University. In
      this case, the small intestine occupied the right half of the abdominal cavity
      and the large intestine occupied the left half. The caecum was situated on the
      anterior inferior part of the abdominal cavity near the midline. The duodenum
      (Du) was fused to the posterior abdominal wall. The small intestine except the Du
      and the ascending colon were suspended from the posterior abdominal wall by the
      mesentery, but the remainder of the colon was fused to the left posterior
      abdominal wall. In addition, an anomalous branch arose from the abdominal aorta
      between the superior and inferior mesenteric arteries (SM and IM) in this case.
      It chiefly supplied the ascending and the transverse colons and anastomosed with
      the SM and IM, respectively, through the marginal arteries. It is very rare that
      these anomalies appear simultaneously in one body. In this case, it is difficult
      to declare that the existence of the MM directly caused the nonrotation of the
      midgut, but it is reasonable to suppose some kind of relation between them.

PMID- 16447908
TI  - Quantitative evaluation of aortic arch development using digital-image analysis.
AB  - This study was performed on 80 spontaneously aborted human fetuses of a
      gestational period of between 17 and 27 weeks. The procedure was based on latex
      filled arteries, which were preserved in formalin, and then later dissected. Data
      collection was accomplished using digital imaging. The specific measurements of
      the aortic arch diameter, length and volume were obtained using a computer
      program, written solely for the purpose of this study. Results indicated that the
      collected figures correlated with the fetal age through 3 sets of 4-week
      intervals. Diameter and length of the aortic arch varied from 2.5 to 4.1 mm and
      from 6.7 to 10.3 mm, respectively. Both parameters showed statistically
      significant (p<0.05) linear growth and differences between age groups. The
      volumetric growth of the aortic arch followed a square root function with its
      values ranging from 35.7 to 136.8 mm3, which were also statistically significant
      (p < 0.05). The diameter of the aortic isthmus was measured and compared to the
      diameters of the ascending and descending aorta thus allowing an estimation ratio
      between those parameters. Concluding analyses suggest that the aortic isthmus
      becomes narrower during fetal development.

PMID- 16447909
TI  - Morphometric study of the aortic and great pulmonary arterial pathways in human
      foetuses.
AB  - In prenatal and pediatric cardiovascular surgery knowledge of luminal diameters
      of the aortic and great pulmonary pathways is essential. The internal diameters
      of the aortic and great pulmonary pathways in 131 human foetuses (65 male, 66
      female) were studied by means of anatomical, digital and statistical methods.
      During foetal development the absolute diameters revealed a linear increase.
      Correlation coefficients between these diameters and foetal age were
      statistically significant (P< or =0.05) for each age group and reached following
      values: r1 = 0.70 for the aortic bulb, r2 = 0.79 for the ascending aorta, r3 =
      0.77 for the aortic isthmus, r4 = 0.79 for the descending aorta, r5 = 0.63 for
      the pulmonary trunk, r6 = 0.36 for the arterial duct, r7 = 0.46 for the right
      pulmonary artery and r8 = 0.49 for the left one. Diameters of the aorta and the
      pulmonary trunk indicated the relative increase in the values. A different
      tendency was observed for the internal diameters of the arterial duct and both
      pulmonary arteries, which were relatively decreased with increased foetal age.
      The largest diameter was observed in the arterial duct, the intermediate--in the
      right pulmonary artery and the smallest--in the left pulmonary artery. The cross
      sectional area of the descending aorta was equal to the sums of the sectional
      areas of the aortic isthmus and the arterial duct (r9 = 0.97). The cross
      sectional area of the pulmonary trunk was equal to the sums of the sectional
      areas of the both pulmonary arteries and the arterial duct (r10 = 0.91).

PMID- 16447910
TI  - A middle meningeal artery which arises from the internal carotid artery in which
      the first branchial artery participates.
AB  - A middle meningeal artery arising from the internal carotid artery was found in
      the right half of the head of an 85-year-old male cadaver during student
      dissection practice. It arose from the lateral aspect of the internal carotid
      artery in the carotid canal, arrived at the foramen lacerum after running
      forward. It then ran backward under the trigeminal ganglion and took the usual
      course after passing its posterior margin. On one hand, the maxillary artery did
      not issue the middle meningeal artery, gave off only a small twig supplying the
      lateral pterygoid muscle at the corresponding position. It was corroborated by
      the fact that the foramen spinosum was absent in this example. During usual
      development, the middle meningeal artery primarily springs from the supraorbital
      branch of the stapedial artery that arises from the dorsal part of the second
      branchial artery. Later, by the formation of the external carotid artery
      connecting with the common trunk of the infraorbital and mandibular branches
      (maxillomandibular division) of the stapedial artery and by the atrophy of the
      proximal part of it, the middle meningeal artery is finally supplied by the
      external carotid artery. But in this example, it is supposed that the middle
      meningeal artery arose from a more distal position of the internal carotid artery
      owing to the persistence of the anastomosis between the dorsal part of the first
      branchial artery and the supraorbital branch and the interruption of the
      connection between the supraorbital branch and maxillomandibular division of the
      stapedial artery.

PMID- 16447911
TI  - Variations of the A. axillaris and the crural arteries in the same human
      individual--multiple repetitions of the mammalian plesiomorphic constellation of
      the arteries.
AB  - While dissecting the body of a 75-year-old female individual we observed
      "abnormal" patterns of the A. axillaris and the crural arteries which resembled
      the mammalian plesiomorphic constellation. In the right arm a large common trunk
      of the A. axillaris gave origin to the A. profunda brachii, the A. circumflexa
      humeri posterior, the A. circumflexa scapulae and the A. thoracodorsalis. In many
      other mammals including non-human primates, the Aa. circumflexae humeri and the
      A. circumflexa scapulae are connected via a third or fourth artery to a common
      trunk. Since the large common trunk mostly corresponded to the supply area of the
      A. axillaris, we consider it to be homologous to the distal part of the A.
      axillaris. In the left arm, except the A. circumflexa humeri posterior and the A.
      subscapularis which take off together, the other axillary branches showed the
      "normal" human pattern. In the right leg, the crural arteries exhibited the
      mammalian plesiomorphic constellation with an A. tibialis anterior ending in the
      crural extensor muscles, a rudimentary A. tibialis posterior, and a strongly
      developed A. peronea. In the left leg, the A. tibialis anterior supplied the
      Dorsum pedis and therefore represented the pattern normally seen in humans.
      However, in the left leg there also was a rudimentary A. tibialis posterior along
      with a prominent A. peronea.

PMID- 16447912
TI  - The inferior supernumerary renal arteries: a classification into three types.
AB  - Among cases that had multiple renal arteries on one side, an inferior
      supernumerary renal artery was found in 24/270 cases (ca. 9%) on the right and in
      19/270 cases (ca. 7%) on the left, together with the usual renal artery. We have
      noticed that there are correlations between their levels of origin from the aorta
      and their positional relation to the ureter and the inferior vena cava (IVC). An
      inferior supernumerary renal artery (InfRA) of lower origin passes in front of
      the IVC and behind the ureter. An InfRA of middle origin passes in front of both
      the IVC and the ureter. An InfRA of upper origin passes behind the IVC and in
      front of the ureter or renal pelvis. In addition there was a tendency for the
      lower origin type to have an ureteric branch, while the middle and upper origin
      types had a gonadal branch. These findings suggest that different derivations
      lead to the inferior supernumerary renal arteries.

PMID- 16447913
TI  - Angioarchitecture of the anterior and medium parts of the palatine mucosa of the
      gerbil, Meriones unguiculatus.
AB  - The aim of this study was to examine the microvasculature of the anterior and
      medium portions of the hard palatine mucosa in the adult gerbil (Meriones
      unguiculatus) using scanning electron microscopy. The vascular corrosion casts
      were obtained by injection of Mercox CL-2B synthetic resin and tissue corrosion
      was performed using sodium hydroxide solution. These casts revealed the presence
      of capillary loops in the palatine plicae and a smoother/flatter vascular network
      in the interplicae areas. The capillary loops consisted mainly of anteriorly
      oriented hair-pins and we also verified a differentiation in the shape of
      endothelial cell nuclei, which were elongated in arterial and circular in venous
      vessels.

PMID- 16447914
TI  - Three-dimensional observation of blood vessels supplying the gland proper and
      capsule of the mouse submandibular gland.
AB  - Previous studies have shown that submandibular glands suffering interruption of
      the blood circulation from the main supplying artery have more surviving
      parenchymal cells in their peripheral portion than in their central portion.
      Although the reason for this difference between the peripheral and central
      portions has not yet been clarified, the existence of collateral circulation has
      been suspected. The present study was designed to examine whether or not the
      vessels binding the gland proper to the capsule provide such collateral
      circulation. Silicone rubber or methacrylate was injected into the main artery
      supplying the mouse submandibular gland, in which the gland proper is wrapped by
      a capsule similar to that of the human submandibular gland, and then the gland
      was observed by both stereoscopic and scanning electron microscopy. Three
      dimensional observations showed no communicating vessels between the gland proper
      and the capsule. Therefore, it is suggested that the parenchymal cells surviving
      in the ischemic peripheral portion of the submandibular gland are nourished by
      permeation of tissue fluid contained in the capsule.

PMID- 16447915
TI  - Relations of the pterygoid hamulus and hard palate in children and adults:
      anatomical implications for the function of the soft palate.
AB  - We investigated spatial relations of the pterygoid hamuli to the hard palate on
      65 skull bases: 31 disarticulated sphenoidal bones from the newborn up to 9 years
      of age, 19 skulls of adult skeletons (21-59 age group), and 15 skulls aged 60-100
      years. We measured: (a) width of the hard palate in the choanal region, (b)
      length of the hamulus, (c) inclination of the hamulus from the perpendicular
      line, and (d) distance between the tips of the contralateral hamuli. The width of
      the hard palate in the choanal region was smallest in children (mean +/- standard
      deviation, 21.5 +/- 2.6 mm) compared with adult skulls (26.8 +/- 2.3 mm in the 21
      59 age group and 25.4 +/- 1.9 mm in the 60-100 age group; P<0.05, one-way
      analysis of variance (ANOVA) and Student-Newman-Keuls post hoc test). Children
      had the shortest hamulus (3.6 +/- 1.5mm), and its length increased in the adult
      age group to 6.9+1.7mm (P<0.05), and then again decreased to 5.0 +/- 1.9 mm in
      the 60-100 age group (P<0.05 vs. adults and children). The distance between the
      tips of the contralateral hamuli and their lateral inclination from the
      perpendicular plane were also greater in the adult age group (38.0 +/- 2.7mm and
      35.9 +/- 13.7 degrees, respectively) than either in children (31.0 +/- 3.7mm and
      19.6 +/- 12.1 degrees) or the elderly (32.7 +/- 3.9mm and 19.7 +/- 10.3 degrees)
      (P<0.05). Our study showed that the anatomical measures of the pterygoid hamulus
      and its relation to the surrounding structures change with age, and occur with
      the changes in the function of pharyngeal and palatal muscles in deglutition.
      These changes may have clinical relevance for sleep apnoea and snoring.

PMID- 16447916
TI  - Neurochemical properties of the middle cervical ganglion in the sheep.
AB  - The neurochemical properties of the ovine middle cervical ganglion (MCG) were
      studied using antibodies raised against tyrosine hydroxylase (TH), dopamine beta
      hydroxylase (DbetaH), neuropeptide Y (NPY), substance P (SP), calcitonin gene
      related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and galanin
      (GAL). Double-labelling immunocytochemistry revealed that the vast majority (95.5
      +/- 0.8%) of postganglionic sympathetic MCG neurons expressed simultaneously both
      catecholamine-synthesizing enzymes (neurons were TH/DbetaH-positive). A large
      population of noradrenergic neurons exhibited immunoreactivity (IR) to NPY (62.2
      +/- 2.2%), but single NPY-positive perikarya-lacking noradrenergic markers were
      also observed (2.0 +/- 0.3%). None of the examined MCG neuronal somata contained
      SP, CGRP, GAL or VIP. A moderate number of noradrenergic nerve fibres located
      amongst neuronal cell bodies was also found. In small number of these terminals
      the presence of NPYor GAL (but not CGRP or VIP) was detected. The ovine MCG was
      numerously innervated with SP-immunoreactive nerve fibres which sometimes formed
      basket-like formations around postganglionic neurons. The MCG exhibited a sparse
      CGRP-immunoreactive innervation and lacked VIP-positive nerve terminals. In many
      aspects the chemical coding of MCG postganglionic neurons and nerve terminals
      resembles that found in other mammalian cervico-thoracic paravertebral ganglia,
      but some important species-dependent differences exist. The functional
      implications of these differences remain to be elucidated.

PMID- 16447917
TI  - Considerations on the phrenic ganglia.
AB  - The phrenic ganglion is described as a small ganglion located at the junction of
      the right phrenic nerve and branches of the celiac plexus, on the diaphragm. The
      descriptions of this ganglion are few and incomplete and justify the present
      study which has been performed macroscopically by dissection and microscopically
      using silver stained (the method of Bielschowsky) drawn pieces. Dissections of 10
      human adult specimens showed one or more ganglia located at the level of the
      terminal division of the right diaphragmatic artery; these ganglia belong to a
      trunk linking the right phrenic nerve and the celiac ganglion. In some specimens
      that nervous trunk was replaced by a ganglionated plexus. That trunk--the
      diaphragmatic nerve--attaches to a distinctive projection of the celiac ganglion;
      it may be double, but there is one ganglionated component. No left phrenic
      ganglia were detected. The macroscopic phrenic ganglia are distributed as
      follows: the lower to the adrenal gland and the upper to the diaphragm.
      Microscopically, the ganglia had autonomic characteristics; intrinsic
      microganglia were also detected within the diaphragmatic nerve. Moreover,
      periadventitial nervous cells were detected on the right inferior phrenic artery.
      IN CONCLUSION: (1) the phrenic ganglia seem to be constant structures on the
      right-hand side; (2) their number is variable--it may be the result of individual
      fragmentation or coalescence during development; (3) these ganglia may be either
      adrenal vasomotor or diaphragmatic vasomotor, and functionally belong to the
      celiac plexus; (4) intrinsic neural and periarterial locations are also possible
      for macroscopically undetectable populations of autonomic nervous cells.

PMID- 16447918
TI  - Can mold allergy be diagnosed with a skin test or specific IgE antibodies?

PMID- 16447919
TI  - Comparison of the skin test and ImmunoCAP system in the evaluation of mold
      allergy.
AB  - BACKGROUND: Mold is ubiquitous in our environment and is a common allergen in
      allergic diseases. The skin test and the Pharmacia ImmunoCAP system (CAP) for
      assay-specific immunoglobulin E (IgE) antibodies are both widely used. The goal
      of this study was to compare the performance of the skin test and CAP in the
      evaluation of mold allergy. METHODS: Patients with allergic rhinitis were
      enrolled at our outpatient department. The diagnosis of allergic rhinitis was
      based on typical symptoms for more than 2 years. All patients were tested by both
      intradermal skin test and serum assay for specific IgE antibodies. The skin test
      included house dust, cotton, ragweed, and 5 fungal antigens (Candida, Alternaria,
      Aspergillus, Cladosporium, and Penicillium). The serum-specific IgE antibodies
      were quantified using the radioimmunoassay version of CAP. RESULTS: Seventy-five
      patients (44 males and 31 females) with allergic rhinitis were enrolled in this
      study. Their ages ranged from 12 to 76 years old, with a mean of 31.9 years. The
      positive rates of skin test and CAP were 56.0% versus 9.3% for Candida, 22.7%
      versus 1.3% for Alternaria, 16% versus 9.3% for Aspergillus, 14.7% versus 1.3%
      for Cladosporium, and 32% versus 8% for Penicillium. There were statistically
      significant differences between the positive rates for Candida, Alternaria,
      Cladosporium, and Penicillium when analyzed by the McNemar test. CONCLUSION: The
      positive rate of the skin test is higher than CAP when evaluating mold allergy.
      Clinicians should note that a discrepancy may exist between the results of in
      vitro and in vivo tests when evaluating mold allergy.

PMID- 16447920
TI  - Analysis of humoral immunity of hepatitis D virus DNA vaccine generated in mice
      by using different dosage, gene gun immunization, and in vivo electroporation.
AB  - BACKGROUND: Hepatitis D virus (HDV) DNA vaccine can produce Th1 and cytotoxic T
      cell immune responses but only a low anti-HDV antibody titer is generated with a
      large hepatitis D antigen (L-HDAg) construct. In contrast, DNA vaccine expressing
      small hepatitis D antigen (S-HDAg) can generate a high titer of anti-HDV
      antibodies. Whether the low humoral immunity of L-HDAg DNA vaccine is due to
      inadequate dosage or can be ameliorated by other modes of immunization needs
      further evaluation. METHODS: Plasmid (p25L) encoding L-HDAg and plasmid (pS/p25L)
      coexpressing hepatitis B surface antigen (HBsAg) and L-HDAg were used in this
      study. We compared the humoral response generated in mice using different plasmid
      DNA dosages and modes of immunization, including gene gun and in vivo
      electroporation (EP). RESULTS: Intramuscular injection with a high dose of
      plasmid DNA (10 mg/kg) produced strong antibodies to HBsAg earlier than the usual
      dose did, but did not augment the anti-HDV response. Gene gun DNA immunization
      could not provide a better humoral immune response to HDV. EP DNA immunization
      had a higher anti-HDV seroconversion rate of 80%, but the anti-HDV antibody
      responses were generally weak (titer < or = 400:1). CONCLUSION: The low humoral
      immunogenicity of DNA vaccine with L-HDAg cannot be ameliorated by different
      dosage, gene gun immunization, or in vivo EP intramuscular injection. DNA vaccine
      with a L-HDAg construct may not be a candidate HDV vaccine to generate anti-HDV
      humoral immunity.

PMID- 16447921
TI  - Prevalence of arteriosclerosis and atherosclerosis in stable patients at a
      cardiovascular outpatient clinic: potential for better care.
AB  - BACKGROUND: Cardiovascular treatment guidelines for stable patients who are
      regularly followed up at medical center clinics have long been practiced and are
      intended to improve arteriosclerosis and atherosclerosis in these patients. The
      present study investigated the prevalence of arteriosclerosis and atherosclerosis
      in patients attending one such clinic, and explored the potential for better
      care. METHODS: A total of 124 outpatients randomly selected from 586 stable
      outpatients on regular visits to the same senior cardiologist were invited to
      receive measurements of brachial-ankle pulse wave velocity (baPWV) and ankle
      brachial index (ABI) using a novel device during their clinic visits. Abnormally
      high baPWV was defined using the age- and sex-stratified reference ranges
      obtained from a previous community survey. RESULTS: The prevalence of high baPWV
      in the studied outpatients was 24.2% and the prevalence of low ABI (< 0.9) was
      8.1%. Based on the reports of baPWV and ABI at the point of care, medications
      were adjusted in 56 patients (45.2%). In 22 patients who had adjusted
      antihypertensive medication and repeat examinations of baPWV and ABI at
      subsequent visits, systolic blood pressure fell by 11 mmHg (p = 0.012), and baPWV
      fell by 0.2 m/s (p = 0.001). CONCLUSION: Abnormal baPWV and ABI are not uncommon
      in stable patients who are regularly followed up at a cardiology clinic where
      treatment guidelines are completely followed. Fast assessment of arteriosclerosis
      and atherosclerosis at the point of care may provide better care for this group
      of patients.

PMID- 16447922
TI  - Transurethral prostatic resection for acute urinary retention in patients with
      prostate cancer.
AB  - BACKGROUND: Few studies have focused on clinical findings in prostate cancer
      patients receiving transurethral resection of the prostate (TURP) for acute
      urinary retention (AUR). We compared the clinical findings (preoperative
      characteristics, operative morbidities, and pathology results) of patients with
      diagnosed prostate cancer undergoing palliative TURP for AUR with those of
      patients undergoing TURP for AUR who were diagnosed with prostate cancer
      postoperatively. METHODS: The charts of 25 patients with prostate cancer
      undergoing TURP for AUR between 1986 and 2003 were retrospectively reviewed.
      Fourteen patients underwent palliative TURP (group A) and the other 11 patients
      with newly diagnosed prostate cancer received TURP (group B). The data, including
      preoperative characteristics, operative morbidities, and pathology results were
      analyzed. RESULTS: There were no significant differences between the 2 groups in
      parameters such as age at diagnosis and operation, operative time,
      hospitalization, and catheter duration. However, the Gleason score was higher in
      group A (7.6 +/- 1.7) than in group B (5.4 +/- 1.8) (p < 0.005). The mean
      resected weight was lower in group A (19.9 g) than in group B (39.5 g). Group A
      was more likely to receive recatheterization (33.3% vs 0%, p = 0.058) and repeat
      operation (28.6%), although the difference was not statistically significant.
      There were no complications such as transurethral resection syndrome or
      perioperative death in either group. CONCLUSION: TURP can be performed safely for
      relief of AUR in patients with prostate cancer, no matter if the cancer was
      diagnosed before or after surgery. The higher Gleason score and more advanced
      cancer stage, as found in group A, may correlate to high recatheterization and
      reoperation rates due to preexisting tumor progression.

PMID- 16447923
TI  - Comparison of plain MRI and MR arthrography in the evaluation of lateral
      ligamentous injury of the ankle joint.
AB  - BACKGROUND: The purpose of this study was to determine the efficacy of plain
      magnetic resonance imaging (MRI) and magnetic resonance (MR) arthrography for
      detecting collateral ligamentous injury of the ankle joint. METHODS: Fifty
      patients (October 2001 to November 2003) suffering from ankle disability who
      underwent plain MRI and MR arthrographic studies were enrolled in this study. The
      diagnostic criteria for ligament disruption on plain MRI included
      nonvisualization, disruption, waviness of the ligament, or coexistent avulsion
      fracture. The MR arthrographic findings of ligament disruption were based on
      leakage of gadolinium contrast medium anterior to the anterior talofibular (ATaF)
      ligament following ATaF ligament disruption, and the contrast medium filling into
      the common peroneal tendon sheath after calcaneofibular (CF) ligament disruption.
      The 2 modalities were interpreted respectively and blindly. RESULTS: Seventeen
      patients received surgical intervention. There were 14 patients who had a torn
      ATaF ligament and 6 patients who suffered from CF ligament disruption proved by
      surgery. Limited detection of preoperative plain MRI survey, which showed 12
      patients had torn ATaF and 2 patients had torn CF ligament, was noted. However,
      most patients with ligamentous injury were correctly diagnosed by MR arthrography
      preoperatively (only 1 case of CF injury was missed). The plain MRI alone had a
      higher incidence of false negative and false positive detection. MR arthrography
      was also valuable for evaluating the coexisting intra-articular pathologies of
      the ankle joint. CONCLUSION: For evaluating ankle disability, using plain MRI
      alone is not adequate for correctly detecting lateral collateral ligamentous
      injury of the ankle joint. MR arthrography improves the sensitivity and the
      accuracy for ATaF and CF ligament injuries. It also helps in assessing coexisting
      pathologic lesions of ankle joints, especially impingement syndromes and
      osteochondral lesions, and provides more information for therapeutic decision
      making.

PMID- 16447924
TI  - Acute effects of dual-chamber pacing on the left ventricular systolic function
      and relaxation in patients with advanced AV block and sick sinus syndrome.
AB  - BACKGROUND: Abnormal activation of the ventricles via right ventricular apical
      pacing deteriorates cardiac function, which may explain the increased mortality
      of patients with congestive heart failure receiving permanent pacemakers. We
      hypothesized that pacing at alternative sites may cause less detrimental effects
      on the cardiac function. METHODS: Five symptomatic patients with either advanced
      AV block (n = 4) or sick sinus syndrome with normal left ventricular (LV)
      function (n = 1) were studied. During cardiac catheterization, LV pressure was
      recorded with a high-fidelity catheter-tipped transducer. Baseline rhythms were
      sinus rhythm or VVI pacing. Sequential VDD pacing with variable AV intervals was
      performed at the right ventricular apex (RVA), right ventricular septum (RVS),
      right ventricular outflow tract (RVOT) and coronary sinus (CS). LV systolic
      function was assessed by calculating dP/dt(max) and LV diastolic function was
      indexed by calculating the exponential isovolumic relaxation constant (Tau).
      Percentage changes (mean +/- SE) from baseline to pacing were measured. RESULTS:
      RVA pacing reduced dP/dt(max) (-0.8 +/- 8.4%) and prolonged Tau (7.0 +/- 5.6%);
      RVS pacing enhanced dP/dt(max) (20.7 +/- 15.3%) and shortened Tau (-10.4 +/- 9%);
      RVOT pacing reduced dP/dt(max) (-8.0 +/- 20.0%) and shortened Tau (-6.0 +/-
      12.2%); CS pacing reduced dP/dt(max) (-11.7 +/- 13.0%) and prolonged Tau (10.5 +/
      11.9%). Our results demonstrated that different pacing sites have different
      effects on LV contractility and relaxation in patients with normal LV function.
      CONCLUSION: Since pacing at the RVS preferably increased LV dP/dt(max) and
      shortened Tau, it may be a better alternative than the RVA.

PMID- 16447925
TI  - Intrathoracic paraspinal malignant peripheral nerve sheath tumor.
AB  - Schwannoma is the most common nerve sheath tumor in the posterior mediastinum,
      whereas intrathoracic paraspinal malignant peripheral nerve sheath tumor (MPNST)
      is quite rare. Both benign and malignant nerve sheath tumors may be symptomatic,
      rendering clinical differentiation of limited utility. On radiographic imaging,
      erosion of the ribs and vertebral bodies, irregularity in contour, and
      inhomogeneity in attenuation are not sufficiently reliable for diagnosis of
      MPNST. Histologically, MPNSTs reveal hypercellularity, nuclear atypia, and
      mitotic activity. Surgical resection is the main modality of treatment.
      Postoperative radiation therapy for MPNST has led to a significant reduction in
      local recurrence. The prognosis is unfavorable. Herein, we present an unusual
      case of a posterior mediastinal mass in a 50-year-old female with delayed
      diagnosis of 2 years. After surgical intervention, the histologic finding was
      MPNST. Postoperative radiation therapy was applied because of incomplete
      resection. The follow-up chest computed tomography 5 months later revealed a
      residual soft tissue mass with significant reduction in size over the
      parathoracic spine area. No neurologic sequelae were identified after surgery.

PMID- 16447926
TI  - Endometriosis associated with hemothorax.
AB  - Bloody pleural effusion is rarely associated with endometriosis. To effectively
      treat this condition, it is important to differentiate the malady from other
      common diseases such as malignancy or tuberculosis. We describe the case of a 40
      year-old multiparous female featuring right-sided hemothorax presenting with
      right shoulder pain and progressive shortness of breath for the preceding 2
      months. Thoracoscopy disclosed grossly negative findings apart from multiple
      small pores in the right hemi-diaphragm with blood clots within them. Examination
      of the thoracoscopic biopsy specimens showed chronic pleuritis without evidence
      of malignancy or tuberculosis. Pelvic endometriosis was considered a possible
      diagnosis according to the results of abdominal computed tomography (CT) scan,
      transvaginal sonography, and the results of dilatation and curettage. Periodic
      episodes of symptoms concurrent with menstruation led to the suspicion of a
      relationship between these conditions in our patient. Despite the patient
      undergoing an abdominal total hysterectomy and adhesiolysis without salpingo
      oophorectomy, recurrent right-sided bloody pleural effusion developed 1.5 months
      subsequent to surgery. As a consequence, danazol (400 mg/day) was maintained
      because of the endometriosis associated with pleural effusion. One year of
      regular follow-up later, there was no evidence of recurrent pleural effusion. We
      considered that the bloody pleural fluid arose via seepage from the pelvic
      endometriosis through the pores of the right hemi-diaphragm during menstruation.

PMID- 16447927
TI  - Extrapelvic endometriosis complicated with colonic obstruction.
AB  - Endometriosis is often seen in gynecology practice and is treated medically.
      However, intestinal involvement of endometriosis causing obstruction is
      relatively uncommon and is hard to differentiate from malignancy before surgery.
      Herein, we present a case of acute colonic obstruction caused by rectal
      endometriosis. Repeat colonoscopic biopsy and imaging studies could not
      differentiate the lesion from malignancy. Segmental resection with anastomosis
      was performed to relieve the symptom and confirm the diagnosis. We present this
      unusual disease in general surgical practice and also review the literature. The
      incidence, symptoms, diagnosis, treatment, and risk of malignancy of intestinal
      endometriosis are discussed.

PMID- 16447928
TI  - Primary retroperitoneal abscess complicated with septic arthritis of the hip.
AB  - Primary retroperitoneal abscess complicated with septic arthritis of the hip is
      an unusual disease. The insidious and occult nature of abscess coexistent with
      arthritis causes diagnostic delays, prolonged sepsis, and considerably higher
      morbidity and mortality. We herein present a case of gouty arthritis and
      avascular necrosis of the femoral head in a 41-year-old woman who complained of
      fever, right flank pain, body weight loss, swelling over her right lower limb,
      and 2 weeks of pain in the right hip. The computed tomographic scan showed a huge
      abscess (about 32 x 10 x 8 cm) over the right posterior pararenal space, with
      swelling of the right psoas, iliac, and obturator muscles. During surgery, the
      abscess was drained and sequestrectomy of the right hip was performed. Cultures
      of pus from the retroperitoneum and right hip showed Escherichia coil and
      Staphylococcus aureus. We review the literature and discuss possible causes.

PMID- 16447929
TI  - Assessing the value of LASIK by patient-reported outcomes using quality of life
      assessment.

PMID- 16447930
TI  - Near vision evaluation considering reading performance.

PMID- 16447931
TI  - Update of presbyopia treatment by scleral ablation using Er:YAG and UV lasers.

PMID- 16447932
TI  - A quality of life comparison of people wearing spectacles or contact lenses or
      having undergone refractive surgery.
AB  - PURPOSE: To demonstrate the use of the Quality of Life Impact of Refractive
      Correction (QIRC) questionnaire for comparing the quality of life of pre
      presbyopic individuals with refractive correction by spectacles, contact lenses,
      or refractive surgery. METHODS: The 20-item QIRC questionnaire was administered
      to 104 spectacle wearers, 104 contact lens wearers, and 104 individuals who had
      undergone refractive surgery (N = 312). These groups were similar for gender,
      ethnicity, socioeconomic status, and refractive error. The main outcome measure
      was QIRC overall score (scaled from 0 to 100), a measure of refractive correction
      related quality of life. Groups were compared for overall QIRC score and on each
      question by analysis of variance, adjusted for age, with post hoc significance
      testing (Sheffe). RESULTS: On average, refractive surgery patients scored
      significantly better (mean QIRC score 50.2 +/- 6.3, F(2,309) = 15.18, P < .001)
      than contact lens wearers (46.7 +/- 5.5, post hoc P < .001) who were in turn
      significantly better than spectacle wearers (44.1 +/- 5.9, post hoc P < .01).
      Convenience questions chiefly drove the differences between groups, although
      functioning, symptoms, economic concerns, heath concerns, and well being were
      also important. Spectacle wearers with low strength prescriptions (46.18 +/-
      5.05) scored significantly better than those with medium strength prescriptions
      (42.74 +/- 6.08, F(2,190) = 3.66, P < .05, post hoc P < .05). A small number (n =
      7, 6.7%) of refractive surgery patients experienced postoperative complications,
      which impacted quality of life (37.86 +/- 2.13). CONCLUSIONS: Quality of life was
      lowest in spectacle wearers, particularly those with higher corrections. Contact
      lens wearers had significantly better QIRC score than spectacle wearers.
      Refractive surgery patients scored significantly better than both. However, this
      was accompanied by a small risk of poor quality of life due to postoperative
      complications. The QIRC is an effective outcome measure for quality of life
      impact of refractive correction.

PMID- 16447933
TI  - Confocal microscopy of disposable and nondisposable heads for the Moria M2
      microkeratome.
AB  - PURPOSE: To study the quality of the flap obtained with two different heads,
      disposable and nondisposable, and two different speeds, low and high, using the
      same Moria M2 microkeratome (Moria, Antony, France). METHODS: In a prospective
      randomized study, 51 consecutive eyes (28 patients) underwent myopic LASIK (-4.39
      +/- 2.15 diopters). The eyes were randomly assigned to four groups related to
      cutting head model (disposable and nondisposable) and cut speed (low and high).
      In all cases, the intended cut was 160 microm and the same M2 unit was used.
      During surgery, superficial measurements of the flap and the surgeon's opinion
      about the quality of the cut were recorded. One month after LASIK, the cut depth,
      interface particle density, and transparency of the cornea (confocal wound
      healing opacity index) were measured with a confocal microscope. RESULTS: Flaps
      performed with a disposable cutting head and high speed were statistically
      significantly larger than the flaps created in the other groups (Kruskal-Wallis
      test; P = .041). No statistical differences were noted in cut depth, number of
      particles, and wound healing opacity index. The surgeon's opinion parameters were
      similar in all groups. CONCLUSIONS: The Moria M2 microkeratome is safe and
      provided reproducible results, regardless of cutting head and speed. Disposable
      and nondisposable head models were similar in their outcome in the quality
      control model used in this study.

PMID- 16447934
TI  - Corneal aberration changes after hyperopic LASIK: a comparison between the VISX
      Star S2 and the Asclepion-Meditec MEL 70 G Scan excimer lasers.
AB  - PURPOSE: To compute and compare anterior corneal aberration changes following
      hyperopic LASIK using two different excimer lasers: the VISX Star S2 and the
      Asclepion-Meditec MEL 70 G Scan. METHODS: The right eyes of 43 patients with
      preoperative refraction ranging from +0.75 to +5.50 diopters (D) and astigmatism
      ranging from 0.00 to 1.00 D were randomly divided into two groups. The first
      group was operated with the Star S2, a broad-beam excimer laser (n = 22), and the
      second group with the MEL 70, a flying-spot excimer laser (n = 21). Total higher
      order aberrations (Z(i), n > or = 3), coma (Z (+/- 1(3)), Z (+/- 1(5)), and
      spherical aberration (Z0(4)) values were computed from videokeratography using CT
      View software preoperatively and 6 months postoperatively, for 3.0- and 6.5-mm
      aperture diameters. RESULTS: Higher order aberrations, coma, and spherical
      aberration increased after hyperopic LASIK and were greater for larger pupil
      diameters in both groups. No statistically significant differences were found
      between the Star S2 and MEL 70 excimer lasers in terms of aberrometric increase,
      mean postoperative visual acuity, and residual refraction. CONCLUSIONS: Anterior
      corneal aberrations increase after hyperopic LASIK. The type of laser (Star S2
      versus MEL 70) seems to have no impact on the amount of anterior corneal
      aberrations induced after hyperopic LASIK.

PMID- 16447935
TI  - LASIK for hyperopia with the WaveLight excimer laser.
AB  - PURPOSE: To evaluate the safety and efficacy of the ALLEGRETTO WAVE excimer laser
      system (WaveLight Laser Technologie AG, Erlangen, Germany) in LASIK for hyperopia
      and hyperopic astigmatism. METHODS: One hundred twenty consecutive LASIK cases
      for hyperopia with or without astigmatism treated with the ALLEGRETTO WAVE
      excimer laser were prospectively evaluated up to 12 months postoperatively.
      Patients were allocated into three groups according to their refractive sphere
      and cylinder: a low hyperopia group, with up to +3.00 diopters (D) sphere and
      astigmatism < or = +1.00 D (n = 52); a moderate hyperopia group with +3.25 to
      +5.00 D sphere and astigmatism of < or = +1.00 D (n = 45); and a high
      hyperopia/toric group with sphere > or = +5.25 D or cylinder > or = +1.25.D (n =
      23). Flaps were created with the Moria M2 microkeratome (Moria, Antony, France).
      Parameters evaluated were pre- and postoperative refractive error, uncorrected
      visual acuity, best spectacle-corrected visual acuity (BSCVA), higher order
      aberration change, and contrast sensitivity. RESULTS: One hundred twelve eyes
      (93%) were available for follow-up at 12 months. Of the eyes in the low hyperopia
      group, 92% were within +/- 0.50 D of the refractive goal. For the moderate sphere
      group and the high hyperopia/toric group, 79% and 71% of eyes, respectively, were
      within +/- 0.50 D of the refractive goal. No eye lost > or = 2 lines of BSCVA. An
      increase in higher order aberrations was noted in the high hyperopia/toric group
      from 0.47 microm (+/- 0.096) to 0.94 microm (+/- 0.167) (P < .001). No
      significant changes in higher order aberrations were noted in the low and
      moderate hyperopia groups. CONCLUSIONS: Hyperopic LASIK using the WaveLight
      ALLEGRETTO WAVE excimer laser appears to be safe and effective in the correction
      of low, moderate, and high hyperopia and hyperopic astigmatism.

PMID- 16447936
TI  - Complex wavefront-guided retreatments with the Alcon CustomCornea platform after
      prior LASIK.
AB  - PURPOSE: To report the results of complex wavefront-guided LASIK retreatments.
      METHODS: Twenty eyes (15 patients) with histories of conventional LASIK surgery
      and significant visual complaints of glare and halos due to higher order
      aberrations were treated. Wavefront-guided retreatments were performed with the
      LADARVision CustomCornea system (Alcon, Ft Worth, Tex). Pre- and postoperative
      topographies, wavefront measurements, and subjective reports were analyzed.
      RESULTS: Postoperatively, patients had an expanded optical zone, many with
      improved centration. Lower and higher order aberrations decreased following
      wavefront-guided ablation. Mean higher order root-mean-square decreased from 1.01
      +/- 0.25 microm preoperatively to 0.84 +/- 0.23 microm postoperatively. Mean coma
      decreased from 0.59 +/- 0.26 microm to 0.43 +/- 0.21 microm. Mean spherical
      aberration decreased from 0.66 +/- 0.25 microm to 0.54 +/- 0.27 microm.
      Subjective reports of glare and halo symptoms improved in all patients.
      CONCLUSIONS: CustomCornea wavefront-guided treatments are effective in reducing
      lower and higher order aberrations, expanding optical zones, and improving
      subjective reports of adverse aberration sequelae such as glare and halos.

PMID- 16447937
TI  - Long-term refractive results of myopic LASIK complicated with intraoperative
      epithelial defects.
AB  - PURPOSE: To evaluate the long-term refractive results of LASIK for myopia
      complicated with intraoperative epithelial defects. METHODS: Twenty-six eyes with
      epithelial defects on the LASIK flap were compared with the contralateral eye
      that had no intraoperative complications. Pre- and postoperative data were
      compared between the two groups including 3-, 6- and 12-month postoperative
      spherical equivalent refraction, amount of undercorrection, and complications.
      RESULTS: Eyes with intraoperative epithelial defects showed more undercorrection
      at 3 and 6 months postoperatively (P < .05). No statistically significant
      difference was noted at 12 months. Twenty (76%) eyes in the epithelial defect
      group lost best spectacle-corrected visual acuity (BSCVA) at 3 months
      postoperatively compared with 2 (7%) eyes in the control group. By 1 year,
      however, only 2 (7%) eyes in the epithelial defect group and no eyes in the
      control group lost > 1 line of BSCVA. Diffuse lamellar keratitis was observed in
      15 (58%) of 26 eyes with epithelial defects and these eyes had more
      undercorrections at 6 and 12 months (P < .05) and higher corneal irregularity
      index at 6 and 12 months compared with controls (P < .05). Eyes with small
      epithelial defects (> 1 mm2 to < 3 mm2) had more undercorrections at 6 months (
      1.08 +/- 0.76 diopters [D]) compared with the control group (-0.46 +/- 0.87 D).
      Eyes with centrally located epithelial defects had more undercorrections and
      increased corneal irregularity index compared with controls (P < .05).
      CONCLUSIONS: Intraoperative epithelial defects after LASIK should be considered a
      severe complication that may result in diffuse lamellar keratitis, induce loss of
      BSCVA, prolong recovery of visual acuity, and induce undercorrection.

PMID- 16447938
TI  - Autologous serum eye drops for dry eye after LASIK.
AB  - PURPOSE: To evaluate the efficacy of autologous serum eye drops for dry eye after
      LASIK in a prospective, randomized study. METHODS: Fifty-four eyes of 27 male
      patients who underwent LASIK were divided into two groups; patients who used
      autologous serum eye drops and those who used artificial tears postoperatively.
      Schirmer test with anesthesia, tear break-up time (BUT), and rose bengal and
      fluorescein staining for the ocular surface were prospectively compared between
      the groups. All values were also compared before and after surgery (at 1 week
      [except for Schirmer test], 1 month, 3 months, and 6 months) in each group.
      RESULTS: Tear BUT was greater in the autologous serum eye drops group than in the
      artificial tears group at 6 months postoperatively. Rose bengal score was lower
      in patients using autologous serum eye drops than in patients using artificial
      tears at 1 month and 3 months postoperatively. No significant difference was
      noted between patients using autologous serum eye drops and patients using
      artificial tears in the value of Schirmer test with anesthesia and fluorescein
      scores. In the autologous serum eye drops group, tear BUT was increased at 3
      months after LASIK, rose bengal score was lower at 1 month and 3 months, and
      fluorescein score was lower at 1 month after LASIK compared to preoperative
      values, respectively. In the artificial tears group, all values (Schirmer test,
      tear BUT, rose bengal score, and fluorescein score) showed no differences between
      before and after LASIK. No differences were noted in the subjective scores for
      dryness between the autologous serum eye drops and artificial tears groups.
      CONCLUSIONS: The autologous serum eye drops group showed prolongation of the tear
      BUT and a reduction in rose bengal staining score.

PMID- 16447939
TI  - Two-step LASIK with topography-guided ablation to correct astigmatism after
      penetrating keratoplasty.
AB  - PURPOSE: To assess the efficacy, predictability, stability, and safety of a two
      step LASIK procedure using topography-guided ablation to correct astigmatism
      after penetrating keratoplasty. METHODS: Fifteen eyes of 15 patients underwent a
      two-step LASIK procedure at the Maggiore Hospital of Bologna, Italy. In the first
      step, a flap was created using the Hansatome microkeratome. In the second step,
      topography-guided ablation using the LaserSight LSX was planned with interactive
      software (CIPTA) once topographical and refractive stabilization had been
      obtained. Uncorrected visual acuity (UCVA), best spectacle-corrected visual
      acuity (BSCVA), cylindrical correction, gain of lines of BSCVA, spherical
      equivalent refraction, and complications were analyzed. RESULTS: Minimum follow
      up was 12 months (range: 12 to 30 months). Uncorrected visual acuity improved in
      all 15 (100%) eyes. At the last postoperative examination, 11 (73%) eyes had UCVA
      > or = 20/40. Nine (60%) eyes were within 1.0 diopter (D) of the attempted
      correction. Mean postoperative astigmatism was -1.67 (range: -3.5 to 0; standard
      deviation: 1.26). Index of success of astigmatic correction was 0.26. No patient
      lost Snellen lines of BSCVA. Intraoperative complications included two buttonhole
      flaps, and postoperative complications included one flap retraction. No further
      laser treatment was needed. CONCLUSIONS: The two-step LASIK procedure using
      topography-guided ablation reduces spherical and cylindrical refractive error due
      to penetrating keratoplasty. Topography-guided ablation also proved to be
      effective in correcting irregular astigmatism.

PMID- 16447940
TI  - Intraocular lens power calculation following LASIK: determination of the new
      effective index of refraction.
AB  - PURPOSE: To determine the new corneal effective index of refraction (rN)
      following LASIK to be used for accurate keratometry reading (K-reading). METHODS:
      A total of 332 eyes that underwent myopic LASIK were divided into two groups
      (group A [n = 137] and group B [n = 1951). In each group, patients were divided
      into four subgroups according to the amount of spherical equivalent refraction of
      myopic LASIK ablation (subgroup 1 [< -4.0 D], subgroup 2 [-4.0 to < -8.0 D],
      subgroup 3 [-8.0 to -12.0 D], and subgroup 4 [> -12.0 D]). In each subgroup of
      group A, K-reading was measured by the clinical history method and the new
      corneal effective index (rN) was determined using paraxial formula: (K-reading =
      (rN-1)/Ra), where Ra is the radius of curvature of the anterior corneal surface.
      In group B, the anterior radius of curvature of the cornea was determined by
      automated K-reading, and K-reading was measured in each subgroup using the new
      effective index in paraxial formula, clinical history method, and automated K
      reading. RESULTS: In group A, the new effective index of refraction was 1.3355,
      1.3286, 1.3237, and 1.3172 in the four subgroups, respectively. In group B, the
      mean K-reading measurements using rN in paraxial formula, clinical history
      method, and automated K-reading were: 40.33 +/- 1.68 D, 40.33 +/- 1.67 D, and
      40.54 +/- 1.69 D, respectively, in subgroup 1; 37.96 +/- 1.26 D, 38.03 +/- 1.38
      D, and 38.98 +/- 1.28 D, respectively, in subgroup 2; 35.77 +/- 1.75 D, 35.84 +/-
      1.85 D, and 37.29 +/- 1.83 D, respectively, in subgroup 3; and 34.03 +/- 1.49 D,
      34.15 +/- 1.84 D, and 36.21 +/- 1.59 D, respectively, in subgroup 4. In all
      subgroups of group B, the results of K-reading obtained using the new effective
      index of refraction were statistically similar to the results obtained by
      clinical history method (P > .05). Automated K-reading statistically
      overestimated the K-reading values in subgroups 2, 3, and 4 of group B (P <
      .001). CONCLUSIONS: The use of the new corneal effective index of refraction
      allows for an accurate derivation of K-reading from the anterior radius of
      curvature.

PMID- 16447941
TI  - Standardized analyses of correction of astigmatism by laser systems that reshape
      the cornea.
AB  - PURPOSE: To develop a minimum set of analyses and a format for presentation of
      outcomes of astigmatism correction by laser systems that reshape the cornea.
      METHODS: An Astigmatism Project group was created under the auspices of the
      American National Standards Institute (ANSI) Z80.11 Working Group on Laser
      Systems for Corneal Reshaping. The Astigmatism Project Group was made up of
      experts in astigmatism analyses from academia, government, and industry. An
      extensive literature review was conducted to identify all currently available
      methodologies for the evaluation of astigmatic outcomes. Project Group members
      discussed the utility of each method and its specific parameters for evaluating
      the effectiveness of astigmatism-correcting devices. They gave consideration to
      unique terminology and analyses required for evaluation of correction of
      astigmatism by laser systems that reshape the comea. RESULTS: The Project Group
      defined a comprehensive list of analysis variables needed for the evaluation of
      astigmatism-correcting devices and generated a mathematical definition for each
      term. They developed a minimum set of analyses needed for evaluation of
      astigmatism treatments by laser systems that reshape the cornea. They established
      methods for calculating the refractive error analysis variables and constructed
      recommended table and graph formats for data presentation. CONCLUSIONS: This
      article contains the recommendations of the Astigmatism Project Group of the
      American National Standards Institute. We propose it as a standard reference for
      astigmatic refractive error analyses for the evaluation of safety and
      effectiveness of laser systems that reshape the cornea.

PMID- 16447942
TI  - The "sandwich technique" for iris-fixated phakic intraocular lens implantation.
AB  - PURPOSE: To describe a new technique of implantation of the Artisan/Verisyse
      phakic intraocular lens (PIOL). METHODS: After PIOL insertion into the anterior
      chamber, a bolus of a high viscosity ophthalmic viscosurgical device (OVD) is
      placed over the optic, separating it widely from the endothelium. RESULTS: The
      technique decreases the chance of endothelial damage during enclavation.
      CONCLUSIONS: A bolus of a high viscosity OVD placed on the anterior surface of
      the Artisan/Verisyse PIOL may make enclavation safer.

PMID- 16447943
TI  - Traumatic dislocation and successful re-enclavation of an Artisan phakic IOL with
      analysis of the endothelium.
AB  - PURPOSE: To present a case of traumatic dislocation of an Ophtec Artisan phakic
      intraocular lens (PIOL) and an analysis of the endothelial cell count. METHODS:
      The patient presented with blurred vision in his left eye after sustaining a brow
      laceration. History included uncomplicated bilateral implantation of an Artisan
      PIOL to correct myopia. RESULTS: The brow laceration was sutured and topical
      dexamethasone 0.1% qid was prescribed. One week after presentation, the PIOL was
      relocated. Postoperatively, endothelial cell count analysis was performed in both
      eyes. CONCLUSIONS: A decrease in the hexagonality of the endothelial cells was
      noted in both eyes, which was substantially lower in the injured eye.

PMID- 16447944
TI  - Anterior stromal puncture in the treatment of loose epithelium after LASIK.
AB  - PURPOSE: To describe anterior stromal puncture, with or without a bandage contact
      lens, as a means to treat LASIK epithelial defects and potentially reduce the
      likelihood of secondary diffuse lamellar keratitis (DLK). METHODS: Six eyes of
      five LASIK patients had their microkeratome pass complicated by loose epithelium,
      central in one case. After repositioning the flap, a 25-gauge needle on a
      tuberculin syringe was used to puncture the anterior corneal stroma to just
      beneath Bowman's layer in the affected area of irregular epithelium. A bandage
      contact lens was placed on two eyes, including the one with loose epithelium
      centrally. RESULTS: Normal appearance of the corneal epithelium was noted by
      postoperative day 1; no eye developed DLK or significant epithelial ingrowth
      postoperatively. All eyes achieved > or = 20/20 vision. CONCLUSIONS: By
      obviating, in select cases, the need for bandage contact lenses, anterior stromal
      puncture could increase patient comfort and remove a potential source of
      infection.

PMID- 16447945
TI  - Phacoemulsification and implantation of an accommodating IOL after PRK.
AB  - PURPOSE: To present a case of phacoemulsification and implantation of an
      accommodating intraocular lens (IOL) in a patient with cataract formation after
      previous refractive surgery. METHODS: A 50-year-old man, who initially had
      photorefractive keratectomy to correct moderate myopia, developed a cataract in
      one eye. He subsequently underwent phacoemulsification and implantation of a 1CU
      accommodating IOL, as he wished to remain spectacle independent. RESULTS: The
      patient's distance vision was fully restored. However, accommodative function,
      which was assessed using subjective and novice objective techniques, was only
      partially restored. CONCLUSIONS: Although the accommodating IOL fully restored
      the patient's distance vision, accommodative function was only partially
      restored.

PMID- 16447946
TI  - [+Gx-tolerance by the Cosmonauts of ISS crews 1, 6-9 and visiting crews 1-7
      aboard Soyuz vehicles].
AB  - Analysis of +Gx tolerance of 15 members of short-term ISS missions and 9 members
      of long-term ISS missions aboard the Soyuz vehicles showed good tolerance during
      insertion and satisfactory during descent provided the use of in-flight
      countermeasures and anti-g suit Kentaur inside the vehicle. Objective data about
      the tolerance of off-nominal +Gx (6.26 and 8.1 G) pointed to a more pronounced
      sinus tachycardia and tachypnea in a ballistic descent following long-duration
      weightlessness as compared with nominal. Physiological deviations were transient,
      functional by character. Cardiac arrhythmia was largely observed during return to
      Earth. Two cosmonauts were found to develop prognostically unfavorable ECG
      indications during off-nominal descent. Main factors in these deviations could be
      age (above 45) and existence of some individual specifics of cardiac rhythm
      regulation. These results emphasize the necessity of more careful screening of
      candidates older than 45 years, as weightlessness may impact their general
      condition and tolerance of g-loads during return to Earth.

PMID- 16447947
TI  - [Comparative characteristics of the gas-exchange parameters during exposure to
      lateral (Gy), longitudinal (Gz) and latero-longitudinal (Gz/Gy) G-loads].
AB  - Subject of the investigation was dynamics of gas-exchange parameters during
      exposure to lateral and laterolongitudinal g-loads (Gy, Gz, Gz/Gy) in a coach
      inclined at 300 from the horizontal with a rigid restraint system. Gy values
      varied between 0.5 and 5.0 units, Gz - between 3.0 and 9.9 units and Gz/Gy -
      between 2.6/1.8 and 5.0/3.0 units. In all instances, growth gradient of the
      radial loads was 1.0 u/s, and a period of exposure was up to 30 s. Comparison of
      the Gz vs. Gy tolerance revealed as a substantial increase of the physiological
      "cost", so a more visible disbalance of the diffusion/perfusion ratio of the
      lung. This is consistent with the gas-exchange data according to which lateral g
      loads are a stronger stress-factor and more challenging for pilots than the
      longitudinal g-loads.

PMID- 16447948
TI  - [The ability for psych self-regulation as a factor in resistance to the stresses
      in extreme conditions of space flight].
AB  - Significance of the ability for psych self-regulation in the context of
      resistance to the stresses of space flight was studied in an experiment with 9
      test-subjects simulating such factors of space flights as 8 to 9-day isolation
      and confinement, some physiological effects of microgravity in a head-down
      position at -8 degrees for 7 d, artificial climate, and implementation of dock
      and piloting operations. Stress resistance, self-regulation, mental performance
      and behavior were assessed with the use of computerized tests "Mirror
      coordinograph", "Relaxometer", and "SOPR-monitoring". The ability to voluntary
      control psych was shown to be favorable to stress-resistance and rapid recovery
      of mental efficiency after the natural decline in consequence of the experimental
      simulation. The ability for psych self-regulation is one of the major criteria of
      professional selection for exposure to extreme conditions.

PMID- 16447949
TI  - [Group psychological investigations using the "gomeostat" method during long
      ground-based experiments].
AB  - Retrospective analysis of the results of two ground-based experiments obtained
      with instrumental model of interdependent activity of group members (Gomeostat)
      fulfilled with the help of an updated technical approach complemented the
      previous scientific data.

PMID- 16447950
TI  - [Results of the psychophysiological investigations of female test-subjects during
      long-term stay in pressurized chamber under the regime of therapeutic
      recompression].
AB  - IBMP has developed and applied protocols of therapeutic recompression of patients
      with delayed admission after the onset of decompression sickness or pulmonary
      barotraumas the occurrence of which increases among recreational divers including
      females. Experiment Rusalka-2004 was performed to validate a therapeutic
      recompression protocol with participation of female test-subjects subjected to
      experimental descents at air pressure of 40 and 80 m H2O (training) and of 70 m
      H2O (experimental) followed by 4 days at 40 to 0 m H2O in a hyperoxic (pO2 = 0.45
      0.5 kgs/cm2) helium-oxygen-nitrogen atmosphere. Psychophysiological
      investigations during the experiment revealed only weak changes of the parameters
      evaluated by the well-being - activity - mood, Spilberg - Khanin, Luscher, and
      proof-read tests. Significant deviations in self-feeling (modified method by
      Dembaut - Rubinstein) and mental performance assessment (Krepelin's tables) were
      associated with the air pressure elevation to 40-80 m H2O both during the
      training and experimental descents, and symptoms of nitrogen narcosis. Based on
      these results, the therapeutic recompression protocol can be recommended for
      treatment of as males, so females.

PMID- 16447951
TI  - [Metabolic and hormonal parameters of humans during long-term hyperbaric exposure
      (the recompression treatment table)].
AB  - Several metabolic and hormonal parameters were evaluated in blood of two human
      subjects during simulation of an extended saturation dive. Increases in creatine
      kinase and an upward trend in cholesterol and glucose were observed after
      decompression. The levels of TTH and thyroxin went up in both subjects during
      exposure. The significant changes in cortisol, ACTH, insulin and C-peptide were a
      fingerprint of stress-reaction. After eight days of recovery most of the
      parameters returned to baseline values. The investigation suggests that the
      recompression treatment table did not cause pathological changes in the
      biochemical and hormonal parameters of humans.

PMID- 16447952
TI  - [Aggregate state of human blood in the period of normobaric interval hypoxic
      training].
AB  - Effects of normobaric interval hypoxic training (NIH) on blood aggregation (BA)
      were studied in 22 male subjects (19 to 50 y.o.) given three types of treatment
      courses with hypoxic mixtures of nitrogen and 10 % oxygen (HGM10): short (5-7
      sessions of six 5-min HGM10 cycles with 5-min intervals for breathing air),
      standard (10 sessions with the six HGM10 cycles), and extended (15 sessions with
      six 7-min HGM10 cycles alternating with 3-min air breathing). The standard and
      extended treatment courses did not lead to the positive BA dynamics and were
      characterized by asynchronous jumping of the rheologic and coagulolithic
      potentials. The standard course produced moderate synchronous dynamics of the
      biochemical and biophysical BA modules at fairly high and essentially equal
      rheologic and coagulolithic potentials and, therefore, proved to be best for
      normal males. NIH was recommended for treatment and prophylaxis in aviation
      medicine as an advanced method to facilitate accommodation to harsh occupational
      environments.

PMID- 16447953
TI  - [Effects of adrenergic substances on the cardiac rhythm and electrical activity
      of the brain in rabbits during hypoxia].
AB  - The paper reports the effects of alpha and beta-adrenergic substances on the
      cardiac rhythm and electrical activity of the brain under the hypoxic conditions.
      beta-adrenergic substances were shown to have a stronger influence on these
      parameters as compared with alpha-adrenergic. The neoepinephrine effects were
      pronounced before "lifting", while the propranolol effects increased "at the
      altitude". Neopinephrine was found to have a stimulating effect on the cerebral
      cortex under the conditions of hypoxia.

PMID- 16447954
TI  - [Muscle atrophy in microgravity and during its simulation].
AB  - Summarized are the results of comparative analysis of morphological changes in
      rat's skeletal muscles after microgravity and its simulation. On completion of
      space flight, hindlimb muscles of rats exhibited atrophy developed in space
      microgravity in consequence of the lack of weight-bearing loads and changes
      solely in the slow anti-g muscles due to the hemodynamic disorders appearing
      after space flight. Immobilization combined with clinostatting cannot be a
      veridical laboratory model of microgravity, as horizontally positioned animals
      still possess weight and, besides, experience severe chronic stress of
      immobilization. Tail suspension with the head-end permanently down and the hind
      limbs out of use appeared the most demonstrative model of the space microgravity
      effects. With this model, the hindlimb muscles underwent changes identical to
      what had been observed in space flown animals. Data of the simulation studies
      suggest stabilization of muscle atrophy at a certain level and an earlier and
      stronger reaction to the hindlimb unloading in young rats as compared to old
      animals. Skeletal muscles in females and males responded to suspension similarly
      in spite of difference in the hormonal status.

PMID- 16447955
TI  - [Effectiveness of the biological action of protons and gamma-radiation on cells
      C3H10T1/2].
AB  - Relative biological effectiveness (RBE) of the therapeutic proton beam with an
      energy of 150 MeV was measured during fractional irradiation of mice fibroblasts
      C3H101 T1/2 by 4.0 Gy per day, 5 d/w with the total dose of 40 Gy. Lethal
      effectiveness of the beam at different points of modified Bragg's peak (width of
      the flat apex = 3.7 cm) was evaluated and effects of acute single gamma-radiation
      (6CO) of cells were investigated. Results were compared with the data of
      fractional irradiation to assess reparation processes. It was shown that
      survivability of the cells in three points of Bragg's peak was essentially the
      same but a bit higher at the point of entry. Proton RBE in the experiment was
      equal to zero relative to gamma-radiation. Difference between fractional and
      acute irradiation leveled off with rising doses; however, the reparative
      processes still had a place even at 20 Gy.

PMID- 16447956
TI  - [Investigation into microcirculation in the vascular bed of healthy people and
      patients at rest and during the LBNP test].
AB  - Computer capillaroscopy during the lower body pressure test (LBNP) provided
      additional information about the effects of orthostasis on blood microcirculation
      and separate estimation of blood velocity in arterial, intermediate and venous
      segments of capillaries. Microcirculation was demonstrated to be sensitive to the
      LBNP exposure as in healthy volunteered subjects, so in ischemic, including
      hypertensive, patients. The highest velocity of capillary blood and the lowest Kv
      were determined in ischemic patients including hypertensive, in whom venous
      velocity in capillaries prevailed over arterial (Kv < 1), whereas in healthy
      subjects Kv never fell below 1. 09. Results of the comparative investigations of
      blood microcirculation in healthy people and patients with various cardiovascular
      problems can be used in clinical and space medicine for assessment of the CVS
      functioning and orthostatic tolerance.

PMID- 16447957
TI  - [Testing and selection of equipment to simulate in-flight telemedicine-assisted
      medical examinations and researches on the ISS Russian segment].
AB  - Analysis of equipment and systems used in telemedicine consultation was fulfilled
      from the perspective of integration into the ISS RS.

PMID- 16447958
TI  - Identifying simple discriminatory gene vectors with an information theory
      approach.
AB  - In the feature selection of cancer classification problems, many existing methods
      consider genes individually by choosing the top genes which have the most
      significant signal-to-noise statistic or correlation coefficient. However the
      information of the class distinction provided by such genes may overlap
      intensively, since their gene expression patterns are similar. The redundancy of
      including many genes with similar gene expression patterns results in highly
      complex classifiers. According to the principle of Occam's razor, simple models
      are preferable to complex ones, if they can produce comparable prediction
      performances to the complex ones. In this paper, we introduce a new method to
      learn accurate and low-complexity classifiers from gene expression profiles. In
      our method, we use mutual information to measure the relation between a set of
      genes, called gene vectors, and the class attribute of the samples. The gene
      vectors are in higher-dimensional spaces than individual genes, therefore, they
      are more diverse, or contain more information than individual genes. Hence, gene
      vectors are more preferable to individual genes in describing the class
      distinctions between samples since they contain more information about the class
      attribute. We validate our method on 3 gene expression profiles. By comparing our
      results with those from literature and other well-known classification methods,
      our method demonstrated better or comparable prediction performances to the
      existing methods, however, with lower-complexity models than existing methods.

PMID- 16447959
TI  - Learning yeast gene functions from heterogeneous sources of data using hybrid
      weighted Bayesian networks.
AB  - We developed a machine learning system for determining gene functions from
      heterogeneous sources of data sets using a Weighted Naive Bayesian Network (WNB).
      The knowledge of gene functions is crucial for understanding many fundamental
      biological mechanisms such as regulatory pathways, cell cycles and diseases. Our
      major goal is to accurately infer functions of putative genes or ORFs (Open
      Reading Frames) from existing databases using computational methods. However,
      this task is intrinsically difficult since the underlying biological processes
      represent complex interactions of multiple entities. Therefore many functional
      links would be missing when only one or two source of data is used in the
      prediction. Our hypothesis is that integrating evidence from multiple and
      complementary sources could significantly improve the prediction accuracy. In
      this paper, our experimental results not only suggest that the above hypothesis
      is valid, but also provide guidelines for using the WNB system for data
      collection, training and predictions. The combined training data sets contain
      information from gene annotations, gene expressions, clustering outputs, keyword
      annotations and sequence homology from public databases. The current system is
      trained and tested on the genes of budding yeast Saccharomyces cerevisiae. Our
      WNB model can also be used to analyze the contribution of each source of
      information toward the prediction performance through the weight training
      process. The contribution analysis could potentially lead to significant
      scientific discovery by facilitating the interpretation and understanding of the
      complex relationships between biological entities.

PMID- 16447960
TI  - Consensus genetic maps: a graph theoretic approach.
AB  - A genetic map is an ordering of genetic markers constructed from genetic linkage
      data for use in linkage studies and experimental design. While traditional
      methods have focused on constructing maps from a single population study,
      increasingly maps are generated for multiple lines and populations of the same
      organism. For example, in crop plants, where the genetic variability is high,
      researchers have created maps for many populations. In the face of these new
      data, we address the increasingly important problem of generating a consensus map
      - an ordering of all markers in the various population studies. In our method,
      each input map is treated as a partial order on a set of markers. To find the
      most consistent order shared between maps, we model the partial orders as
      directed graphs. We create an aggregate by merginging the transitive closure of
      the input graphs and taking the transitive reduction of the result. In this
      process, cycles may need to be broken to resolve inconsistencies between the
      inputs. The cycle breaking problem is NP-hard, but the problem size depends upon
      the scope of the inconsistency between the input graphs, which will be local if
      the input graphs are from closely related organisms. We present results of
      running the resulting software on maps generated from seven populations of the
      crop plant Zea Mays.

PMID- 16447961
TI  - Gene teams with relaxed proximity constraint.
AB  - Functionally related genes co-evolve, probably due to the strong selection
      pressure in evolution. Thus we expect that they are present in multiple genomes.
      Physical proximity among genes, known as gene team, is a very useful concept to
      discover functionally related genes in multiple genomes. However, there are also
      many gene sets that do not preserve physical proximity. In this paper, we
      generalized the gene team model, that looks for gene clusters in a physically
      clustered form, to multiple genome cases with relaxed constraint. We propose a
      novel hybrid pattern model that combines the set and the sequential pattern
      models. Our model searches for gene clusters with and/or without physical
      proximity constraint. This model is implemented and tested with 97 genomes (120
      replicons). The result was analyzed to show the usefulness of our model.
      Especially, analysis of gene clusters that belong to B. subtilis and E. coli
      demonstrated that our model predicted many experimentally verified operons and
      functionally related clusters. Our program is fast enough to provide a sevice on
      the web at http://platcom. informatics.indiana.edu/platcom/. Users can select any
      combination of 97 genomes to predict gene teams.

PMID- 16447962
TI  - Efficient algorithms and software for detection of full-length LTR
      retrotransposons.
AB  - LTR retrotransposons constitute one of the most abundant classes of repetitive
      elements in eukaryotic genomes. In this paper, we present a new algorithm for
      detection of full-length LTR retrotransposons in genomic sequences. The algorithm
      identifies regions in a genomic sequence that show structural characteristics of
      LTR retrotransposons. Three key components distinguish our algorithm from that of
      current software - (i) a novel method that preprocesses the entire genomic
      sequence in linear time and produces high quality pairs of LTR candidates in
      running time that is constant per pair, (ii) a thorough alignment-based
      evaluation of candidate pairs to ensure high quality prediction, and (iii) a
      robust parameter set encompassing both structural constraints and quality
      controls providing users with a high degree of flexibility. Validation of both
      our serial and parallel implementations of the algorithm against the yeast genome
      indicates both superior quality and performance results when compared to existing
      software.

PMID- 16447963
TI  - Islands of tractability for parsimony haplotyping.
AB  - We study the parsimony approach to haplotype inference, which calls for finding a
      set of haplotypes of minimum cardinality that explains an input set of genotypes.
      We prove that the problem is APX-hard even in very restricted cases. On the
      positive side, we identify islands of tractability for the problem, by focusing
      on instances with specific structure of haplotype sharing among the input
      genotypes. We exploit the structure of those instance to give polynomial and
      constant-approximation algorithms to the problem. We also show that the general
      parsimony haplotyping problem is fixed parameter tractable.

PMID- 16447964
TI  - Accurate prediction of orthologous gene groups in microbes.
AB  - We present a new computational method for the prediction of orthologous gene
      groups for microbial genomes based on the prediction of co-occurrences of
      homologous genes. The method is inspired by the observation that homologous genes
      are highly likely to be orthologous if their neighboring genes are also
      homologous. Based on co-occurrences of homologous genes, we have grouped the
      (predicted) operons of 77 selected sequenced microbial genomes so that operons of
      the same group are highly likely to be functionally similar or related. We then
      cluster the homologous genes in the same operon group so that genes of the same
      cluster are highly likely to be similar in terms of their sequences and
      functions, i.e., they are predicted to be orthologous genes. By comparing our
      predicted orthologous gene groups with the COG assignments and NCBI annotations,
      we conclude that our method is promising to provide more accurate and specific
      predictions than the existing methods.

PMID- 16447965
TI  - Motif extraction and protein classification.
AB  - We present a novel unsupervised method for extracting meaningful motifs from
      biological sequence data. This de novo motif extraction (MEX) algorithm is data
      driven, finding motifs that are not necessarily over-represented in the data.
      Applying MEX to the oxidoreductases class of enzymes, containing approximately
      7000 enzyme sequences, a relatively small set of motifs is obtained. This set
      spans a motif-space that is used for functional classification of the enzymes by
      an SVM classifier. The classification based on MEX motifs surpasses that of two
      other SVM based methods: SVMProt, a method based on the analysis of physical
      chemical properties of a protein generated from its sequence of amino acids, and
      SVM applied to a Smith-Waterman distances matrix. Our findings demonstrate that
      the MEX algorithm extracts relevant motifs, supporting a successful sequence-to
      function classification.

PMID- 16447966
TI  - Discriminative discovery of transcription factor binding sites from location
      data.
AB  - MOTIVATION: The availability of genome-wide location analyses based on chromatin
      immunoprecipitation (ChIP) data gives a new insight for in silico analysis of
      transcriptional regulations. RESULTS: We propose a novel discriminative discovery
      framework for precisely identifying transcriptional regulatory motifs from both
      positive and negative samples (sets of upstream sequences of both bound and
      unbound genes by a transcription factor (TF)) based on the genome-wide location
      data. In this framework, our goal is to find such discriminative motifs that best
      explain the location data in the sense that the motifs precisely discriminate the
      positive samples from the negative ones. First, in order to discover an initial
      set of discriminative substrings between positive and negative samples, we apply
      a decision tree learning method which produces a text-classification tree. We
      extract several clusters consisting of similar substrings from the internal nodes
      of the learned tree. Second, we start with initial profile-HMMs constructed from
      each cluster for representing putative motifs and iteratively refine the profile
      HMMs to improve the discrimination accuracies. Our genome-wide experimental
      results on yeast show that our method successfully identifies the consensus
      sequences for known TFs in the literature and further presents significant
      performances for discriminating between positive and negative samples in all the
      TFs, while most other motif detecting methods show very poor performances on the
      problem of discriminations. Our learned profile-HMMs also improve false negative
      predictions of ChIP data.

PMID- 16447967
TI  - Reconstructing phylogenetic networks using maximum parsimony.
AB  - Phylogenies - the evolutionary histories of groups of organisms - are one of the
      most widely used tools throughout the life sciences, as well as objects of
      research within systematics, evolutionary biology, epidemiology, etc. Almost
      every tool devised to date to reconstruct phylogenies produces trees; yet it is
      widely understood and accepted that trees oversimplify the evolutionary histories
      of many groups of organims, most prominently bacteria (because of horizontal gene
      transfer) and plants (because of hybrid speciation). Various methods and criteria
      have been introduced for phylogenetic tree reconstruction. Parsimony is one of
      the most widely used and studied criteria, and various accurate and efficient
      heuristics for reconstructing trees based on parsimony have been devised. Jotun
      Hein suggested a straightforward extension of the parsimony criterion to
      phylogenetic networks. In this paper we formalize this concept, and provide the
      first experimental study of the quality of parsimony as a criterion for
      constructing and evaluating phylogenetic networks. Our results show that, when
      extended to phylogenetic networks, the parsimony criterion produces promising
      results. In a great majority of the cases in our experiments, the parsimony
      criterion accurately predicts the numbers and placements of non-tree events.

PMID- 16447968
TI  - An efficient algorithm for Perfect Phylogeny Haplotyping.
AB  - The Perfect Phylogeny Haplotyping (PPH) problem is one of the many computational
      approaches to the Haplotype Inference (HI) problem. Though there are many
      O(nm(2)) solutions to the PPH problem, the complexity of the PPH problem itself
      has remained an open question. In this paper, We introduce the FlexTree data
      structure that represents all the solutions for a PPH instance. We also introduce
      row-ordering that arranges the genotypes in a more manageable fashion. The column
      ordering, the FlexTree data structure and the row ordering together make the
      O(nm) OPPH algorithm possible. We also present some results on simulated data
      which demonstrate that the OPPH algorithm performs quiet impressively when
      compared to the earlier O(nm(2)) algorithms.

PMID- 16447969
TI  - TreeRefiner: a tool for refining a multiple alignment on a phylogenetic tree.
AB  - We present TreeRefiner, a tool for refining multiple alignments of biological
      sequences. Given a multiple alignment, a phylogenetic tree, and scoring
      parameters as input, TreeRefiner optimizes the sum-of-pairs function in a
      restricted three-dimensional space around the alignment. At each internal node of
      the unrooted tree, the multiple alignment is projected to the sub-alignments
      corresponding to the three neighboring nodes, and three-dimensional dynamic
      programming is performed within a user-specified radius r around the original
      alignment. We test TreeRefiner on simulated sequences aligned by several popular
      tools, and demonstrate substantial improvements in the percentage of correctly
      aligned positions.

PMID- 16447970
TI  - Multi-metric and multi-substructure biclustering analysis for gene expression
      data.
AB  - A good number of biclustering algorithms have been proposed for grouping gene
      expression data. Many of them have adopted matrix norms to define the similarity
      score of a bicluster. We shall show that almost all matrix metrics can be
      converted into vector norms while preserving the rank equivalence. Vector norms
      provide a much more efficient vehicle for biclustering analysis and computation.
      The advantages are two folds: ease of analysis and saving of computation. Most
      existing biclustering algorithms have also implicitly assumed the use of
      univariate (i.e., single metric) evaluation for identifying biclusters. Such an
      approach however overlooks the fundamental principle that genes (even though they
      may belong to the same gene group) (1) may be subdivided into different
      substructures; and (2) they may be co-expressed via a diversity of coherence
      models (a gene may participate in multiple pathways that may or may not be co
      active under all conditions). The former leads to the adoption of a multi
      substurcture analysis, while the latter to the multivariate analysis. This paper
      will show that the proposed multivariate and multi-subscluster analysis is very
      effective in identifying and classifying biologically relevant groups in genes
      and conditions. For example, it has successfully yielded highly discriminant and
      accurate classification based on known ribosomal gene groups.

PMID- 16447971
TI  - Analysis of SNP-expression association matrices.
AB  - High throughput expression profiling and genotyping technologies provide the
      means to study the genetic determinants of population variation in gene
      expression variation. In this paper we present a general statistical framework
      for the simultaneous analysis of gene expression data and SNP genotype data
      measured for the same cohort. The framework consists of methods to associate
      transcripts with SNPs affecting their expression, algorithms to detect subsets of
      transcripts that share significantly many associations with a subset of SNPs, and
      methods to visualize the identified relations. We apply our framework to SNP
      expression data collected from 49 breast cancer patients. Our results demonstrate
      an overabundance of transcript-SNP associations in this data, and pinpoint SNPs
      that are potential master regulators of transcription. We also identify several
      statistically significant transcript-subsets with common putative regulators that
      fall into well-defined functional categories.

PMID- 16447972
TI  - A learned comparative expression measure for affymetrix genechip DNA microarrays.
AB  - Perhaps the most common question that a microarray study can ask is, "Between two
      given biological conditions, which genes exhibit changed expression levels?"
      Existing methods for answering this question either generate a comparative
      measure based upon a static model, or take an indirect approach, first estimating
      absolute expression levels and then comparing the estimated levels to one
      another. We present a method for detecting changes in gene expression between two
      samples based on data from Affymetrix GeneChips. Using a library of over 200,000
      known cases of differential expression, we create a learned comparative
      expression measure (LCEM) based on classification of probe-level data patterns as
      changed or unchanged. LCEM uses perfect match probe data only; mismatch probe
      values did not prove to be useful in this context. LCEM is particularly powerful
      in the case of small microarry studies, in which a regression-based method such
      as RMA cannot generalize, and in detecting small expression changes. At the
      levels of selectivity that are typical in microarray analysis, the LCEM shows a
      lower false discovery rate than either MAS5 or RMA trained from a single chip.
      When many chips are available to RMA, LCEM performs better on two out of the
      three data sets, and nearly as well on the third. Performance of the MAS5 log
      ratio statistic was notably bad on all datasets.

PMID- 16447973
TI  - Identification of post-translational modifications via blind search of mass
      spectra.
AB  - Post-translational modifications (PTMs) are of great biological importance. Most
      existing approaches perform a restrictive search that can only take into account
      a few types of PTMs and ignore all others. We describe an unrestrictive PTM
      search algorithm that searches for all types of PTMs at once in a blind mode,
      i.e., without knowing which PTMs exist in a sample. The blind PTM identification
      opens a possibility to study the extent and frequencies of different types of
      PTMs, still an open problem in proteomics. Using our new algorithm, we were able
      to construct a two-dimensional PTM frequency matrix that reflects the number of
      MS/MS spectra in a sample for each putative PTM type and each amino acid.
      Application of this approach to a large IKKb dataset resulted in the largest set
      of PTMs reported for a single MS/MS sample so far. We demonstrate an excellent
      correlation between high values in the PTM frequency matrix and known PTMs thus
      validating our approach. We further argue that the PTM frequency matrix may
      reveal some still unknown modifications that warrant further experimental
      validation.

PMID- 16447975
TI  - Peptide charge state determination for low-resolution tandem mass spectra.
AB  - Mass spectrometry is a particularly useful technology for the rapid and robust
      identification of peptides and proteins in complex mixtures. Peptide sequences
      can be identified by correlating their observed tandem mass spectra (MS/MS) with
      theoretical spectra of peptides from a sequence database. Unfortunately, to
      perform this search the charge of the peptide must be known, and current
      chargestate- determination algorithms only discriminate singlyfrom multiply
      charged spectra: distinguishing +2 from +3, for example, is unreliable. Thus,
      search software is forced to search multiply-charged spectra multiple times. To
      minimize this inefficiency, we present a support vector machine (SVM) that
      quickly and reliably classifies multiplycharged spectra as having either a +2 or
      +3 precursor peptide ion. By classifying multiply-charged spectra, we obtain a
      40% reduction in search time while maintaining an average of 99% of peptide and
      99% of protein identifications originally obtained from these spectra.

PMID- 16447974
TI  - Discover true association rates in multi-protein complex proteomics data sets.
AB  - Experimental processes to collect and process proteomics data are increasingly
      complex, while the computational methods to assess the quality and significance
      of these data remain unsophisticated. These challenges have led to many
      biological oversights and computational misconceptions. We developed a complete
      empirical Bayes model to analyze multi-protein complex (MPC) proteomics data
      derived from peptide mass spectrometry detections of purified protein complex
      pull-down experiments. Our model considers not only bait-prey associations, but
      also prey-prey associations missed in previous work. Using our model and a yeast
      MPC proteomics data set, we estimated that there should be an average of 28 true
      associations per MPC, almost ten times as high as was previously estimated. For
      data sets generated to mimic a real proteome, our model achieved on average 80%
      sensitivity in detecting true associations, as compared with the 3% sensitivity
      in previous work, while maintaining a comparable false discovery rate of 0.3%.

PMID- 16447976
TI  - An efficient and accurate algorithm for assigning nuclear overhauser effect
      restraints using a rotamer library ensemble and residual dipolar couplings.
AB  - Nuclear Overhauser effect (NOE) distance restraints are the main experimental
      data from protein nuclear magnetic resonance (NMR) spectroscopy for computing a
      complete three dimensional solution structure including sidechain conformations.
      In general, NOE restraints must be assigned before they can be used in a
      structure determination program. NOE assignment is very time-consuming to do
      manually, challenging to fully automate, and has become a key bottleneck for high
      throughput NMR structure determination. The difficulty in automated NOE
      assignment is ambiguity: there can be tens of possible different assignments for
      an NOE peak based solely on its chemical shifts. Previous automated NOE
      assignment approaches rely on an ensemble of structures, computed from a subset
      of all the NOEs, to iteratively filter ambiguous assignments. These algorithms
      are heuristic in nature, provide no guarantees on solution quality or running
      time, and are slow in practice. In this paper we present an accurate, efficient
      NOE assignment algorithm. The algorithm first invokes the algorithm in [30, 29]
      to compute an accurate backbone structure using only two backbone residual
      dipolar couplings (RDCs) per residue. The algorithm then filters ambiguous NOE
      assignments by merging an ensemble of intra-residue vectors from a protein
      rotamer database, together with internuclear vectors from the computed backbone
      structure. The protein rotamer database was built from ultra-high resolution
      structures (<1.0 A) in the Protein Data Bank (PDB). The algorithm has been
      successfully applied to assign more than 1,700 NOE distance restraints with
      better than 90% accuracy on the protein human ubiquitin using real experimentally
      recorded NMR data. The algorithm assigns these NOE restraints in less than one
      second on a single-processor workstation.

PMID- 16447977
TI  - Multi-scale hierarchical structure prediction of helical transmembrane proteins.
AB  - As the first step toward a multi-scale, hierarchical computational approach for
      membrane protein structure prediction, the packing of transmembrane helices was
      modeled at the residual and atomistic levels, respectively. For predictions at
      the residual level, the helix-helix and helix-lipid interactions were described
      by a set of knowledge-based energy functions. For predictions at the atomistic
      level, CHARMM19 force field was employed. To facilitate the system to overcome
      energy barriers, Wang-Landau sampling was carried out by performing a random walk
      in the energy and conformational spaces. Native-like structures were predicted at
      both levels for 2- and 7-helix systems. Interestingly, consistent results were
      obtained from simulations at residual and atomistic levels for the same system,
      strongly suggesting the feasibility of a hierarchical approach for membrane
      structure prediction.

PMID- 16447978
TI  - Deformable modeling for improved calculation of molecular velocities from single
      particle tracking.
AB  - Single-particle tracking provides a powerful technique for measuring dynamic
      cellular processes on the level of individual molecules. Much recent work has
      been devoted to using single particle tracking to measure long-range movement of
      particles on the cell surface, including methods for automated localization and
      tracking of particles [1-3]. However, most particle tracking studies to date
      ignore cell surface curvature and dynamic cellular deformation, factors
      frequently present in physiologically relevant situations. In this report, we
      perform quantitative evaluation of single-particle tracking on curved and
      deforming cell surfaces. We also introduce a new hybrid method that uses non
      rigid cellular modeling for improved computation of single-particle tracking
      trajectories on the surfaces of cells undergoing deformation. This method
      combines single-molecule and bulk fluorescence measurements in an automated
      manner to enable more accurate and robust characterization of dynamic cell
      physiology and regulation.

PMID- 16447979
TI  - PSIST: indexing protein structures using suffix trees.
AB  - Approaches for indexing proteins, and for fast and scalable searching for
      structures similar to a query structure have important applications such as
      protein structure and function prediction, protein classification and drug
      discovery. In this paper, we developed a new method for extracting the local
      feature vectors of protein structures. Each residue is represented by a triangle,
      and the correlation between a set of residues is described by the distances
      between Calpha atoms and the angles between the normals of planes in which the
      triangles lie. The normalized local feature vectors are indexed using a suffix
      tree. For all query segments, suffix trees can be used effectively to retrieve
      the maximal matches, which are then chained to obtain alignments with database
      proteins. Similar proteins are selected by their alignment score against the
      query. Our results shows classification accuracy up to 97.8% and 99.4% at the
      superfamily and class level according to the SCOP classification, and shows that
      on average 7.49 out of 10 proteins from the same superfamily are obtained among
      the top 10 matches. These results are competitive with the best previous methods.

PMID- 16447980
TI  - Tree decomposition based fast search of RNA structures including pseudoknots in
      genomes.
AB  - Searching genomes for RNA secondary structure with computational methods has
      become an important approach to the annotation of non-coding RNAs. However, due
      to the lack of efficient algorithms for accurate RNA structure-sequence
      alignment, computer programs capable of fast and effectively searching genomes
      for RNA secondary structures have not been available. In this paper, a novel RNA
      structure profiling model is introduced based on the notion of a conformational
      graph to specify the consensus structure of an RNA family. Tree decomposition
      yields a small tree width t for such conformation graphs (e.g., t = 2 for stem
      loops and only a slight increase for pseudo-knots). Within this modelling
      framework, the optimal alignment of a sequence to the structure model corresponds
      to finding a maximum valued isomorphic subgraph and consequently can be
      accomplished through dynamic programming on the tree decomposition of the
      conformational graph in time O(k(t)N(2)), where k is a small parameter; and N is
      the size of the projiled RNA structure. Experiments show that the application of
      the alignment algorithm to search in genomes yields the same search accuracy as
      methods based on a Covariance model with a significant reduction in computation
      time. In particular; very accurate searches of tmRNAs in bacteria genomes and of
      telomerase RNAs in yeast genomes can be accomplished in days, as opposed to
      months required by other methods. The tree decomposition based searching tool is
      free upon request and can be downloaded at our site h t t p ://w.uga.edu/RNA
      informatics/software/index.php.

PMID- 16447981
TI  - An algebraic geometry approach to protein structure determination from NMR data.
AB  - Our paper describes the first provably-efficient algorithm for determining
      protein structures de novo, solely from experimental data. We show how the global
      nature of a certain kind of NMR data provides quantifiable complexity-theoretic
      benefits, allowing us to classify our algorithm as running in polynomial time.
      While our algorithm uses NMR data as input, it is the first polynomial-time
      algorithm to compute high-resolution structures de novo using any experimentally
      recorded data, from either NMR spectroscopy or X-Ray crystallography. Improved
      algorithms for protein structure determination are needed, because currently, the
      process is expensive and time-consuming. For example, an area of intense research
      in NMR methodology is automated assignment of nuclear Overhauser effect (NOE)
      restraints, in which structure determination sits in a tight inner-loop (cycle)
      of assignment/refinement. These algorithms are very time-consuming, and typically
      require a large cluster. Thus, algorithms for protein structure determination
      that are known to run in polynomial time and provide guarantees on solution
      accuracy are likely to have great impact in the long-term. Methods stemming from
      a technique called "distance geometry embedding" do come with provable
      guarantees, but the NP-hardness of these problem formulations implies that in the
      worst case these techniques cannot run in polynomial time. We are able to avoid
      the NP-hardness by (a) some mild assumptions about the protein being studied, (b)
      the use of residual dipolar couplings (RDCs) instead of a dense network of NOEs,
      and (c) novel algorithms and proofs that exploit the biophysical geometry of (a)
      and (b), drawing on a variety of computer science, computational geometry, and
      computational algebra techniques. In our algorithm, RDC data, which gives global
      restraints on the orientation of internuclear bond vectors, is used in
      conjunction with very sparse NOE data to obtain a polynomial-time algorithm for
      protein structure determination. An implementation of our algorithm has been
      applied to 6 different real biological NMR data sets recorded for 3 proteins. Our
      algorithm is combinatorially precise, polynomial-time, and uses much less NMR
      data to produce results that are as good or better than previous approaches in
      terms of accuracy of the computed structure as well as running time. In practice
      approaches such as restrained molecular dynamics and simulated annealing, which
      lack both combinatorial precision and guarantees on running time and solution
      quality, are commonly used. Our results show that by using a different "slice" of
      the data, an algorithm that is polynomial time and that has guarantees about
      solution quality can be obtained. We believe that our techniques can be extended
      and generalized for other structure-determination problems such as computing side
      chain conformations and the structure of nucleic acids from experimental data.

PMID- 16447982
TI  - A tree-decomposition approach to protein structure prediction.
AB  - This paper proposes a tree decomposition of protein structures, which can be used
      to efficiently solve two key subproblems of protein structure prediction: protein
      threading for backbone prediction and protein side-chain prediction. To develop a
      unified tree-decomposition based approach to these two subproblems, we model them
      as a geometric neighborhood graph labeling problem. Theoretically, we can have a
      low-degree polynomial time algorithm to decompose a geometric neighborhood graph
      G = (V, E) into components with size O(|V|((2/3))log|V|). The computational
      complexity of the tree-decomposition based graph labeling algorithms is
      O(|V|Delta(tw+1)) where Delta is the average number of possible labels for each
      vertex and tw( = O(|V|((2/3))log|V|)) the tree width of G. Empirically, tw is
      very small and the tree-decomposition method can solve these two problems very
      efficiently. This paper also compares the computational efficiency of the tree
      decomposition approach with the linear programming approach to these two problems
      and identifies the condition under which the tree-decomposition approach is more
      efficient than the linear programming approach. Experimental result indicates
      that the tree-decomposition approach is more efficient most of the time.

PMID- 16447983
TI  - A pivoting algorithm for metabolic networks in the presence of thermodynamic
      constraints.
AB  - A linear programming algorithm is presented to constructively compute
      thermodynamically feasible fluxes and change in chemical potentials of reactions
      for a metabolic network. It is based on physical laws of mass conservation and
      the second law of thermodynamics that all chemical reactions should satisfy. As a
      demonstration, the algorithm has been applied to the core metabolic pathway of E.
      coli.

PMID- 16447984
TI  - A topological measurement for weighted protein interaction network.
AB  - High-throughput methods for detecting protein-protein interactions (PPI) have
      given researchers an initial global picture of protein interactions on a genomic
      scale. The usefulness of this understanding is, however, typically compromised by
      noisy data. The effective way of integrating and using these non-congruent data
      sets has received little attention to date. This paper proposes a model to
      integrate different data sets. We construct this model using our prior knowledge
      of data set reliability. Based on this model, we propose a topological
      measurement to select reliable interactions and to quantify the similarity
      between two proteins' interaction profiles. Our measurement exploits the small
      world network topological properties of protein interaction network. Meanwhile,
      we discovered some additional properties of the network. We show that our
      measurement can be used to find reliable interactions with improved performance
      and to find protein pairs with higher function homogeneity.

PMID- 16447985
TI  - Application of a generalized MWC model for the mathematical simulation of
      metabolic pathways regulated by allosteric enzymes.
AB  - In our effort to elucidate the systems biology of the model organism, Escherichia
      coli, we have developed a mathematical model that simulates the allosteric
      regulation for threonine biosynthesis pathway starting from aspartate. To achieve
      this goal, we used kMech, a Cellerator language extension that describes enzyme
      mechanisms for the mathematical modeling of metabolic pathways. These mechanisms
      are converted by Cellerator into ordinary differential equations (ODEs) solvable
      by Mathematica. In this paper, we describe a more flexible model in Cellerator,
      which generalizes the Monod, Wyman, Changeux (MWC) model for enzyme allosteric
      regulation to allow for multiple substrate, activator and inhibitor binding
      sites. Furthermore, we have developed a model that describes the behavior of the
      bifunctional allosteric enzyme aspartate Kinase I-Homoserine Dehydrogenase I (AKI
      HDHI). This model predicts the partition of enzyme activities in the steady state
      which paves a way for a more generalized prediction of the behavior of
      bifunctional enzymes.

PMID- 16447986
TI  - Estimating time-dependent gene networks from time series microarray data by
      dynamic linear models with Markov switching.
AB  - In gene network estimation from time series microarray data, dynamic models such
      as differential equations and dynamic Bayesian networks assume that the network
      structure is stable through all time points, while the real network might changes
      its structure depending on time, affection of some shocks and so on. If the true
      network structure underlying the data changes at certain points, the fitting of
      the usual dynamic linear models fails to estimate the structure of gene network
      and we cannot obtain efficient information from data. To solve this problem, we
      propose a dynamic linear model with Markov switching for estimating time
      dependent gene network structure from time series gene expression data. Using our
      proposed method, the network structure between genes and its change points are
      automatically estimated. We demonstrate the effectiveness of the proposed method
      through the analysis of Saccharomyces cerevisiae cell cycle time series data.

PMID- 16447987
TI  - Choosing SNPs using feature selection.
AB  - A major challenge for genomewide disease association studies is the high cost of
      genotyping large number of single nucleotide polymorphisms (SNP). The
      correlations between SNPs, however, make it possible to select a parsimonious set
      of informative SNPs, known as "tagging" SNPs, able to capture most variation in a
      population. Considerable research interest has recently focused on the
      development of methods for finding such SNPs. In this paper, we present an
      efficient method for finding tagging SNPs. The method does not involve
      computation-intensive search for SNP subsets but discards redundant SNPs using a
      feature selection algorithm. In contrast to most existing methods, the method
      presented here does not limit itself to using only correlations between SNPs in
      local groups. By using correlations that occur across different chromosomal
      regions, the method can reduce the number of globally redundant SNPs.
      Experimental results show that the number of tagging SNPs selected by our method
      is smaller than by using block-based methods.

PMID- 16447988
TI  - Robust and accurate cancer classification with gene expression profiling.
AB  - Robust and accurate cancer classification is critical in cancer treatment. Gene
      expression profiling is expected to enable us to diagnose tumors precisely and
      systematically. However, the classification task in this context is very
      challenging because of the curse of dimensionality and the small sample size
      problem. In this paper, we propose a novel method to solve these two problems.
      Our method is able to map gene expression data into a very low dimensional space
      and thus meets the recommended samples to features per class ratio. As a result,
      it can be used to classify new samples robustly with low and trustable
      (estimated) error rates. The method is based on linear discriminant analysis
      (LDA). However, the conventional LDA requires that the within-class scatter
      matrix S(w) be nonsingular. Unfortunately, Sw is always singular in the case of
      cancer classification due to the small sample size problem. To overcome this
      problem, we develop a generalized linear discriminant analysis (GLDA) that is a
      general, direct, and complete solution to optimize Fisher's criterion. GLDA is
      mathematically well-founded and coincides with the conventional LDA when S(w) is
      nonsingular. Different from the conventional LDA, GLDA does not assume the
      nonsingularity of S(w), and thus naturally solves the small sample size problem.
      To accommodate the high dimensionality of scatter matrices, a fast algorithm of
      GLDA is also developed. Our extensive experiments on seven public cancer datasets
      show that the method performs well. Especially on some difficult instances that
      have very small samples to genes per class ratios, our method achieves much
      higher accuracies than widely used classification methods such as support vector
      machines, random forests, etc.

PMID- 16447989
TI  - A robust meta-classification strategy for cancer diagnosis from gene expression
      data.
AB  - One of the major challenges in cancer diagnosis from microarray data is to
      develop robust classification models which are independent of the analysis
      techniques used and can combine data from different laboratories. We propose a
      meta-classification scheme which uses a robust multivariate gene selection
      procedure and integrates the results of several machine learning tools trained on
      raw and pattern data. We validate our method by applying it to distinguish
      diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL) on two
      independent datasets: the HuGeneFL Affmetrixy dataset of Shipp et al. (www.
      genome.wi.mit.du/MPR /lymphoma) and the Hu95Av2 Affymetrix dataset (DallaFavera's
      laboratory, Columbia University). Our meta-classification technique achieves
      higher predictive accuracies than each of the individual classifiers trained on
      the same dataset and is robust against various data perturbations. We also find
      that combinations of p53 responsive genes (e.g., p53, PLK1 and CDK2) are highly
      predictive of the phenotype.

PMID- 16447990
TI  - Clustering genes using gene expression and text literature data.
AB  - Clustering of gene expression data is a standard technique used to identify
      closely related genes. In this paper, we develop a new clustering algorithm, MSC
      (Multi-Source Clustering), to perform exploratory analysis using two or more
      diverse sources of data. In particular, we investigate the problem of improving
      the clustering by integrating information obtained from gene expression data with
      knowledge extracted from biomedical text literature. In each iteration of
      algorithm MSC, an EM-type procedure is employed to bootstrap the model obtained
      from one data source by starting with the cluster assignments obtained in the
      previous iteration using the other data sources. Upon convergence, the two
      individual models are used to construct the final cluster assignment. We compare
      the results of algorithm MSC for two data sources with the results obtained when
      the clustering is applied on the two sources of data separately. We also compare
      it with that obtained using the feature level integration method that performs
      the clustering after simply concatenating the features obtained from the two data
      sources. We show that the z-scores of the clustering results from MSC are better
      than that from the other methods. To evaluate our clusters better, function
      enrichment results are presented using terms from the Gene Ontology database.
      Finally, by investigating the success of motif detection programs that use the
      clusters, we show that our approach integrating gene expression data and text
      data reveals clusters that are biologically more meaningful than those identified
      using gene expression data alone.

PMID- 16447991
TI  - Bioinformatic insights from metagenomics through visualization.
AB  - Cutting-edge biological and bioinformatics research seeks a systems perspective
      through the analysis of multiple types of high-throughput and other experimental
      data for the same sample. Systems-level analysis requires the integration and
      fusion of such data, typically through advanced statistics and mathematics.
      Visualization is a complementary computational approach that supports integration
      and analysis of complex data or its derivatives. We present a bioinformatics
      visualization prototype, Juxter, which depicts categorical information derived
      from or assigned to these diverse data for the purpose of comparing patterns
      across categorizations. The visualization allows users to easily discern
      correlated and anomalous patterns in the data. These patterns, which might not be
      detected automatically by algorithms, may reveal valuable information leading to
      insight and discovery. We describe the visualization and interaction capabilities
      and demonstrate its utility in a new field, metagenomics, which combines
      molecular biology and genetics to identify and characterize genetic material from
      multi-species microbial samples.

PMID- 16447992
TI  - On optimizing distance-based similarity search for biological databases.
AB  - Similarity search leveraging distance-based index structures is increasingly
      being used for both multimedia and biological database applications. We consider
      distance-based indexing for three important biological data types, protein k-mers
      with the metric PAM model, DNA k-mers with Hamming distance and peptide
      fragmentation spectra with a pseudo-metric derived from cosine distance. To date,
      the primary driver of this research has been multimedia applications, where
      similarity functions are often Euclidean norms on high dimensional feature
      vectors. We develop results showing that the character of these biological
      workloads is different from multimedia workloads. In particular, they are not
      intrinsically very high dimensional, and deserving different optimization
      heuristics. Based on MVP-trees, we develop a pivot selection heuristic seeking
      centers and show it outperforms the most widely used corner seeking heuristic.
      Similarly, we develop a data partitioning approach sensitive to the actual data
      distribution in lieu of median splits.

PMID- 16447993
TI  - Computational method for temporal pattern discovery in biomedical genomic
      databases.
AB  - With the rapid growth of biomedical research databases, opportunities for
      scientific inquiry have expanded quickly and led to a demand for computational
      methods that can extract biologically relevant patterns among vast amounts of
      data. A significant challenge is identifying temporal relationships among
      genotypic and clinical (phenotypic) data. Few software tools are available for
      such pattern matching, and they are not interoperable with existing databases. We
      are developing and validating a novel software method for temporal pattern
      discovery in biomedical genomics. In this paper, we present an efficient and
      flexible query algorithm (called TEMF) to extract statistical patterns from time
      oriented relational databases. We show that TEMF - as an extension to our modular
      temporal querying application (Chronus II) - can express a wide range of complex
      temporal aggregations without the need for data processing in a statistical
      software package. We show the expressivity of TEMF using example queries from the
      Stanford HIV Database.

PMID- 16447994
TI  - Investigation into biomedical literature classification using support vector
      machines.
AB  - Specific topic search in the PubMed Database, one of the most important
      information resources for scientific community, presents a big challenge to the
      users. The researcher typically formulates boolean queries followed by scanning
      the retrieved records for relevance, which is very time consuming and error
      prone. We applied Support Vector Machines (SVM) for automatic retrieval of PubMed
      articles related to Human genome epidemiological research at CDC (Center for
      disease Control and Prevention). In this paper, we discuss various investigations
      into biomedical literature classification and analyze the effect of various
      issues related to the choice of keywords, training sets, kernel functions and
      parameters for the SVM technique. We report on the various factors above to show
      that SVM is a viable technique for automatic classification of biomedical
      literature into topics of interest such as epidemiology, cancer, birth defects
      etc. In all our experiments, we achieved high values of PPV, sensitivity and
      specificity.

PMID- 16447995
TI  - Automated validation of polymerase chain reactions using amplicon melting curves.
AB  - PCR, the polymerase chain reaction, is a fundamental tool of molecular biology.
      Quantitative PCR is the gold-standard methodology for determination of DNA copy
      numbers, quantitating transcription, and numerous other applications. A major
      barrier to large-scale application of PCR for quantitative genomic analyses is
      the current requirement for manual validation of individual PCR reactions to
      ensure generation of a single product. This typically requires visual inspection
      either of gel electrophoreses or temperature dissociation ("melting") curves of
      individual PCR reactions - a time-consuming and costly process. Here we describe
      a robust computational solution to this fundamental problem. Using a training set
      of 10,080 reactions comprising multiple quantitative PCR reactions from each of
      1,728 unique human genomic amplicons, we developed a support vector machine
      classifier capable of discriminating single-product PCR reactions with better
      than 99% accuracy. This approach has broad utility, and eliminates a major
      bottleneck to widespread application of PCR for high-throughput genomic
      applications.

PMID- 16447996
TI  - Shannon information in complete genomes.
AB  - Shannon information in the genomes of all completely sequenced prokaryotes and
      eukaryotes are measured in word lengths of two to ten letters. It is found that
      in a scale-dependent way, the Shannon information in complete genomes are much
      greater than that in matching random sequences - thousands of times greater in
      the case of short words. Furthermore, with the exception of the 14 chromosomes of
      Plasmodium falciparum, the Shannon information in all available complete genomes
      belong to a universality class given by an extremely simple formula. The data are
      consistent with a model for genome growth composed of two main ingredients:
      random segmental duplications that increase the Shannon information in a scale
      independent way, and random point mutations that preferentially reduces the
      larger-scale Shannon information. The inference drawn from the present study is
      that the large-scale and coarse-grained growth of genomes was selectively neutral
      and this suggests an independent corroboration of Kimura's neutral theory of
      evolution.

PMID- 16447997
TI  - Segmental duplications containing tandem repeated genes encoding putative
      deubiquitinating enzymes.
AB  - Both inter- and intra-chromosomal segmental duplications are known occurred in
      human genome during evolution. Few cases of such segments involving functional
      genes have been reported. While searching for the human orthologs of murine
      hematopoietic deubiquitinating enzymes (DUBs), we identified four clusters of DUB
      like genes on chromosome 4p15 and chromosome 8p22-23 that are over 90% identical
      to each other at the DNA level. These genes are expressed in a cell type- and
      activation-specific manner, with different clusters possessing potentially
      distinct expression profiles. Examining the surrounding sequences of these gene
      duplication events, we have identified previously unreported conserved sequence
      elements that are as large as 35 to 74 kb encircling the gene clusters. Traces of
      these elements are also found on chromosome 12p13 and chromosome 11q13. The
      coding and immediate upstream sequences for DUB-like genes as well as the
      surrounding conserved elements, are present in the chimpanzee trace database, but
      not in rodent genome. We hypothesize that the segments containing these DUB
      clusters and surrounding elements arose relatively recently in evolution through
      inter- and intra-chromosomal duplicative transpositions, following the divergence
      of primates and rodents. Genome wide systematical search of the segmental
      duplication containing duplicated gene cluster has been performed.

PMID- 16447998
TI  - Recurrence time statistics: versatile tools for genomic DNA sequence analysis.
AB  - With the completion of the human and a few model organisms' genomes, and the
      genomes of many other organisms waiting to be sequenced, it has become
      increasingly important to develop faster computational tools which are capable of
      easily identifying the structures and extracting features from DNA sequences. One
      of the more important structures in a DNA sequence is repeat-related. Often they
      have to be masked before protein coding regions along a DNA sequence are to be
      identified or redundant expressed sequence tags (ESTs) are to be sequenced. Here
      we report a novel recurrence time based method for sequence analysis. The method
      can conveniently study all kinds of periodicity and exhaustively find all repeat
      related features from a genomic DNA sequence. An efficient codon index is also
      derived from the recurrence time statistics, which has the salient features of
      being largely species-independent and working well on very short sequences.
      Efficient codon indices are key elements of successful gene finding algorithms,
      and are particularly useful for determining whether a suspected EST belongs to a
      coding or non-coding region. We illustrate the power of the method by studying
      the genomes of E. coli, the yeast S. cervisivae, the nematode worm C. elegans,
      and the human, Homo sapiens. Computationally, our method is very efficient. It
      allows us to carry out analysis of genomes on the whole genomic scale by a PC.

PMID- 16447999
TI  - FastR: fast database search tool for non-coding RNA.
AB  - The discovery of novel non-coding RNAs has been among the most exciting recent
      developments in Biology. Yet, many more remain undiscovered. It has been
      hypothesized that there is in fact an abundance of functional non-coding RNA
      (ncRNA) with various catalytic and regulatory functions. Computational methods
      tailored specifically for ncRNA are being actively developed. As the inherent
      signal for ncRNA is weaker than that for protein coding genes, comparative
      methods offer the most promising approach, and are the subject of our research.
      We consider the following problem: Given an RNA sequence with a known secondary
      structure, efficiently compute all structural homologs (computed as a function of
      sequence and structural similarity) in a genomic database. Our approach, based on
      structural filters that eliminate a large portion of the database, while
      retaining the true homologs allows us to search a typical bacterial database in
      minutes on a standard PC, with high sensitivity and specificity. This is two
      orders of magnitude better than current available software for the problem.

PMID- 16448000
TI  - Compressed pattern matching in DNA sequences.
AB  - We propose derivative Boyer-Moore (d-BM), a new compressed pattern matching
      algorithm in DNA sequences. This algorithm is based on the Boyer-Moore method,
      which is one of the most popular string matching algorithms. In this approach, we
      compress both DNA sequences and patterns by using two bits to represent each A,
      T, C, G character. Experiments indicate that this compressed pattern matching
      algorithm searches long DNA patterns (length > 50) more than 10 times faster than
      the exact match routine of the software package Agrep, which is known as the
      fastest pattern matching tool. Moreover, compression of DNA sequences by this
      method gives a guaranteed space saving of 75%. In part the enhanced speed of the
      algorithm is due to the increased efficiency of the Boyer-Moore method resulting
      from an increase in alphabet size from 4 to 256.

PMID- 16448001
TI  - A self-tuning method for one-chip SNP identification.
AB  - Current methods for interpreting oligonucleotide-based SNP-detection microarrays,
      SNP chips, are based on statistics and require extensive parameter tuning as well
      as extremely high-resolution images of the chip being processed. We present a
      method, based on a simple data-classification technique called nearest-neighbors
      that, on haploid organisms, produces results comparable to the published results
      of the leading statistical methods and requires very little in the way of
      parameter tuning. Furthermore, it can interpret SNP chips using lower-resolution
      scanners of the type more typically used in current microarray experiments. Along
      with our algorithm, we present the results of a SNP-detection experiment where,
      when independently applying this algorithm to six identical SARS SNP chips, we
      correctly identify all 24 SNPs in a particular strain of the SARS virus, with
      between 6 and 13 false positives across the six experiments.

PMID- 16448002
TI  - Space-conserving optimal DNA-protein alignment.
AB  - DNA-protein alignment algorithms can be used to discover coding sequences in a
      genomic sequence, if the corresponding protein derivatives are known. They can
      also be used to identify potential coding sequences of a newly sequenced genome,
      by using proteins from related species. Previously known algorithms either solve
      a simplified formulation, or sacrifice optimality to achieve practical
      implementation. In this paper, we present a comprehensive formulation of the DNA
      protein alignment problem, and an algorithm to compute the optimal alignment in
      O(mn) time using only four tables of size (m + 1) x (n + 1), where m and n are
      the lengths of the DNA and protein sequences, respectively. We also developed a
      Protein and DNA Alignment program PanDA that implements the proposed solution.
      Experimental results indicate that our algorithm produces high quality
      alignments.

PMID- 16448003
TI  - Algorithms for association study design using a generalized model of haplotype
      conservation.
AB  - There is considerable interest in computational methods to assist in the use of
      genetic polymorphism data for locating disease-related genes. Haplotypes,
      contiguous sets of correlated variants, may provide a means of reducing the
      difficulty of the data analysis problems involved. The field to date has been
      dominated by methods based on the "haplotype block" hypothesis, which assumes
      discrete population-wide boundaries between conserved genetic segments, but there
      is strong reason to believe that haplotype blocks do not fully capture true
      haplotype conservation patterns. In this paper, we address the computational
      challenges of using a more flexible, block-free representation of haplotype
      structure called the "haplotype motif" model for downstream analysis problems. We
      develop algorithms for htSNP selection and missing data inference using this more
      generalized model of sequence conservation. Application to a dataset from the
      literature demonstrates the practical value of these block-free methods.

PMID- 16448004
TI  - Rec-I-DCM3: a fast algorithmic technique for reconstructing large phylogenetic
      trees.
AB  - Phylogenetic trees are commonly reconstructed based on hard optimization problems
      such as maximum parsimony (MP) and maximum likelihood (ML). Conventional MP
      heuristics for producing phylogenetic trees produce good solutions within
      reasonable time on small datasets (up to a few thousand sequences), while ML
      heuristics are limited to smaller datasets (up to a few hundred sequences).
      However, since MP (and presumably ML) is NP-hard, such approaches do not scale
      when applied to large datasets. In this paper, we present a new technique called
      Recursive-Iterative-DCM3 (Rec-I-DCM3), which belongs to our family of Disk
      Covering Methods (DCMs). We tested this new technique on ten large biological
      datasets ranging from 1,322 to 13,921 sequences and obtained dramatic speedups as
      well as significant improvements in accuracy (better than 99.99%) in comparison
      to existing approaches. Thus, high-quality reconstructions can be obtained for
      datasets at least ten times larger than was previously possible.

PMID- 16448005
TI  - MinPD: distance-based phylogenetic analysis and recombination detection of
      serially-sampled HIV quasispecies.
AB  - A new computational method to study within-host viral evolution is explored to
      better understand the evolution and pathogenesis of viruses. Traditional
      phylogenetic tree methods are better suited to study relationships between
      contemporaneous species, which appear as leaves of a phylogenetic tree. However,
      viral sequences are often sampled serially from a single host. Consequently, data
      may be available at the leaves as well as the internal nodes of a phylogenetic
      tree. Recombination may further complicate the analysis. Such relationships are
      not easily expressed by traditional phylogenetic methods. We propose a new
      algorithm, called MinPD, based on minimum pairwise distances. Our algorithm uses
      multiple distance matrices and correlation rules to output a MinPD tree or
      network. We test our algorithm using extensive simmulations and apply it to a set
      of HIV sequence data isolated from one patient over a period of ten years. The
      proposed visualization of the phylogenetic tree?network further enhances the
      benefits of our methods.

PMID- 16448006
TI  - Gridding and compression of microarray images.
AB  - With the recent explosion of interest in microarray technology, massive amounts
      of microarray images are currently being produced. The storage and the
      transmission of this type of data are becoming increasingly challenging. Here we
      propose lossless and lossy compression algorithms for microarray images
      originally digitized at 16 bpp (bits per pixels) that achieve an average of 9.5 -
      11.5 bpp (lossless) and 4.6 - 6.7 bpp (lossy, with a PSNR of 63 dB). The lossy
      compression is applied only on the background of the image, thereby preserving
      the regions of interest. The methods are based on a completely automatic gridding
      procedure of the image.

PMID- 16448007
TI  - A theoretical analysis of gene selection.
AB  - A great deal of recent research has focused on the challenging task of selecting
      differentially expressed genes from microarray data ('gene selection'). Numerous
      gene selection algorithms have been proposed in the literature, but it is often
      unclear exactly how these algorithms respond to conditions like small sample
      sizes or differing variances. Choosing an appropriate algorithm can therefore be
      difficult in many cases. In this paper we propose a theoretical analysis of gene
      selection, in which the probability of successfully selecting relevant genes,
      using a given gene ranking function, is explicitly calculated in terms of
      population parameters. The theory developed is applicable to any ranking function
      which has a known sampling distribution, or one which can be approximated
      analytically. In contrast to empirical methods, the analysis can easily be used
      to examine the behaviour of gene selection algorithms under a wide variety of
      conditions, even when the numbers of genes involved runs into the tens of
      thousands. The utility of our approach is illustrated by comparing three well
      known gene ranking functions.

PMID- 16448008
TI  - Minimum entropy clustering and applications to gene expression analysis.
AB  - Clustering is a common methodology for analyzing the gene expression data. In
      this paper, we present a new clustering algorithm from an information-theoretic
      point of view. First, we propose the minimum entropy (measured on a posteriori
      probabilities) criterion, which is the conditional entropy of clusters given the
      observations. Fano's inequality indicates that it could be a good criterion for
      clustering. We generalize the criterion by replacing Shannon's entropy with
      Havrda-Charvat's structural alpha-entropy. Interestingly, the minimum entropy
      criterion based on structural alpha-entropy is equal to the probability error of
      the nearest neighbor method when alpha = 2. This is another evidence that the
      proposed criterion is good for clustering. With a non-parametric approach for
      estimating a posteriori probabilities, an efficient iterative algorithm is then
      established to minimize the entropy. The experimental results show that the
      clustering algorithm performs significantly better than k-means/medians,
      hierarchical clustering, SOM, and EM in terms of adjusted Rand index.
      Particularly, our algorithm performs very well even when the correct number of
      clusters is unknown. In addition, most clustering algorithms produce poor
      partitions in presence of outliers while our method can correctly reveal the
      structure of data and effectively identify outliers simultaneously.

PMID- 16448009
TI  - Profile-based string kernels for remote homology detection and motif extraction.
AB  - We introduce novel profile-based string kernels for use with support vector
      machines (SVMs) for the problems of protein classification and remote homology
      detection. These kernels use probabilistic profiles, such as those produced by
      the PSI-BLAST algorithm, to define position-dependent mutation neighborhoods
      along protein sequences for inexact matching of k-length subsequences ("k-mers")
      in the data. By use of an efficient data structure, the kernels are fast to
      compute once the profiles have been obtained. For example, the time needed to run
      PSI-BLAST in order to build the pro- files is significantly longer than both the
      kernel computation time and the SVM training time. We present remote homology
      detection experiments based on the SCOP database where we show that profile-based
      string kernels used with SVM classifiers strongly outperform all recently
      presented supervised SVM methods. We also show how we can use the learned SVM
      classifier to extract "discriminative sequence motifs" -- short regions of the
      original profile that contribute almost all the weight of the SVM classification
      score -- and show that these discriminative motifs correspond to meaningful
      structural features in the protein data. The use of PSI-BLAST profiles can be
      seen as a semi-supervised learning technique, since PSI-BLAST leverages unlabeled
      data from a large sequence database to build more informative profiles. Recently
      presented "cluster kernels" give general semi-supervised methods for improving
      SVM protein classification performance. We show that our profile kernel results
      are comparable to cluster kernels while providing much better scalability to
      large datasets.

PMID- 16448010
TI  - A mixed factors model for dimension reduction and extraction of a group structure
      in gene expression data.
AB  - When we cluster tissue samples on the basis of genes, the number of observations
      to be grouped is much smaller than the dimension of feature vector. In such a
      case, the applicability of conventional model-based clustering is limited since
      the high dimensionality of feature vector leads to overfitting during the density
      estimation process. To overcome such difficulty, we attempt a methodological
      extension of the factor analysis. Our approach enables us not only to prevent
      from the occurrence of overfitting, but also to handle the issues of clustering,
      data compression and extracting a set of genes to be relevant to explain the
      group structure. The potential usefulness are demonstrated with the application
      to the leukemia dataset.

PMID- 16448011
TI  - MISAE: a new approach for regulatory motif extraction.
AB  - The recognition of regulatory motifs of co-regulated genes is essential for
      understanding the regulatory mechanisms. However, the automatic extraction of
      regulatory motifs from a given data set of the upstream non-coding DNA sequences
      of a family of co-regulated genes is difficult because regulatory motifs are
      often subtle and inexact. This problem is further complicated by the corruption
      of the data sets. In this paper, a new approach called Mismatch-allowed
      Probabilistic Suffix Tree Motif Extraction (MISAE) is proposed. It combines the
      mismatch-allowed probabilistic suffix tree that is a probabilistic model and
      local prediction for the extraction of regulatory motifs. The proposed approach
      is tested on 15 co-regulated gene families and compares favorably with other
      state-of-the-art approaches. Moreover, MISAE performs well on "corrupted" data
      sets. It is able to extract the motif from a "corrupted" data set with less than
      one fourth of the sequences containing the real motif.

PMID- 16448012
TI  - Biclustering in gene expression data by tendency.
AB  - The advent of DNA microarray technologies has revolutionized the experimental
      study of gene expression. Clustering is the most popular approach of analyzing
      gene expression data and has indeed proven to be successful in many applications.
      Our work focuses on discovering a subset of genes which exhibit similar
      expression patterns along a subset of conditions in the gene expression matrix.
      Specifically, we are looking for the Order Preserving clusters (OPCluster), in
      each of which a subset of genes induce a similar linear ordering along a subset
      of conditions. The pioneering work of the OPSM model[3], which enforces the
      strict order shared by the genes in a cluster, is included in our model as a
      special case. Our model is more robust than OPSM because similarly expressed
      conditions are allowed to form order equivalent groups and no restriction is
      placed on the order within a group. Guided by our model, we design and implement
      a deterministic algorithm, namely OPCTree, to discover OP-Clusters. Experimental
      study on two real datasets demonstrates the effectiveness of the algorithm in the
      application of tissue classification and cell cycle identification. In addition,
      a large percentage of OP-Clusters exhibit significant enrichment of one or more
      function categories, which implies that OP-Clusters indeed carry significant
      biological relevance.

PMID- 16448013
TI  - Improved fourier transform method for unsupervised cell-cycle regulated gene
      prediction.
AB  - MOTIVATION: Cell-cycle regulated gene prediction using microarray time-course
      measurements of the mRNA expression levels of genes has been used by several
      researchers. The popularly employed approach is Fourier transform (FT) method in
      conjunction with the set of known cell-cycle regulated genes. In the absence of
      training data, fourier transform method is sensitive to noise, additive monotonic
      component arising from cell population growth and deviation from strict
      sinusoidal form of expression. Known cell cycle regulated genes may not be
      available for certain organisms or using them for training may bias the
      prediction. RESULTS: In this paper we propose an Improved Fourier Transform (IFT)
      method which takes care of several factors such as monotonic additive component
      of the cell-cycle expression, irregular or partial-cycle sampling of gene
      expression. The proposed algorithm does not need any known cell-cycle regulated
      genes for prediction. Apart from alleviating need for training set, it also
      removes bias towards genes similar to the training set. We have evaluated the
      developed method on two publicly available datasets: yeast cell-cycle data and
      HeLa cell-cycle data. The proposed algorithm has performed competitively on both
      datasets with that of the supervised fourier transform method used. It
      outperformed other unsupervised methods such as Partial Least Squares (PLS) and
      Single Pulse Modeling (SPM). This method is easy to comprehend and implement, and
      runs faster.

PMID- 16448014
TI  - SPIDER: software for protein identification from sequence tags with de novo
      sequencing error.
AB  - For the identification of novel proteins using MS/MS, de novo sequencing software
      computes one or several possible amino acid sequences (called sequence tags) for
      each MS/MS spectrum. Those tags are then used to match, accounting amino acid
      mutations, the sequences in a protein database. If the de novo sequencing gives
      correct tags, the homologs of the proteins can be identified by this approach and
      software such as MS-BLAST is available for the matching. However, de novo
      sequencing very often gives only partially correct tags. The most common error is
      that a segment of amino acids is replaced by another segment with approximately
      the same masses. We developed a new efficient algorithm to match sequence tags
      with errors to database sequences for the purpose of protein and peptide
      identification. A software package, SPIDER, was developed and made available on
      Internet for free public use. This paper describes the algorithms and features of
      the SPIDER software.

PMID- 16448015
TI  - Estimating and improving protein interaction error rates.
AB  - High throughput protein interaction data sets have proven to be notoriously
      noisy. Although it is possible to focus on interactions with higher reliability
      by using only those that are backed up by two or more lines of evidence, this
      approach invariably throws out the majority of available data. A more optimal use
      could be achieved by incorporating the probabilities associated with all
      available interactions into the analysis. We present a novel method for
      estimating error rates associated with specific protein interaction data sets, as
      well as with individual interactions given the data sets in which they appear. As
      a bonus, we also get an estimate for the total number of protein interactions in
      yeast. Certain types of false positive results can be identified and removed,
      resulting in a significant improvement in quality of the data set. For co
      purification data sets, we show how we can reach a tradeoff between the "spoke"
      and "matrix" representation of interactions within co-purified groups of proteins
      to achieve an optimal false positive error rate.

PMID- 16448016
TI  - Automated protein classification using consensus decision.
AB  - We propose a novel technique for automatically generating the SCOP classification
      of a protein structure with high accuracy. High accuracy is achieved by combining
      the decisions of multiple methods using the consensus of a committee (or an
      ensemble) classifier. Our technique is rooted in machine learning which shows
      that by judicially employing component classifiers, an ensemble classifier can be
      constructed to outperform its components. We use two sequence- and three
      structure-comparison tools as component classifiers. Given a protein structure,
      using the joint hypothesis, we first determine if the protein belongs to an
      existing category (family, superfamily, fold) in the SCOP hierarchy. For the
      proteins that are predicted as members of the existing categories, we compute
      their family-, superfamily-, and fold-level classifications using the consensus
      classifier. We show that we can significantly improve the classification accuracy
      compared to the individual component classifiers. In particular, we achieve error
      rates that are 3-12 times less than the individual classifiers' error rates at
      the family level, 1.5-4.5 times less at the superfamily level, and 1.1-2.4 times
      less at the fold level.

PMID- 16448017
TI  - Separation of ion types in tandem mass spectrometry data interpretation -- a
      graph-theoretic approach.
AB  - Mass spectrometry is one of the most popular analytical techniques for
      identification of individual proteins in a protein mixture, one of the basic
      problems in proteomics. It identifies a protein through identifying its unique
      mass spectral pattern. While the problem is theoretically solvable, it remains a
      challenging problem computationally. One of the key challenges comes from the
      difficulty in distinguishing the N- and C-terminus ions, mostly b- and y-ions
      respectively. In this paper, we present a graph algorithm for solving the problem
      of separating bfrom y-ions in a set of mass spectra. We represent each spectral
      peak as a node and consider two types of edges: a type-1 edge connects two peaks
      possibly of the same ion types and a type-2 edge connects two peaks possibly of
      different ion types, predicted based on local information. The ion-separation
      problem is then formulated and solved as a graph partition problem, which is to
      partition the graph into three subgraphs, namely b-, y-ions and others
      respectively, so to maximize the total weight of type-1 edges while minimizing
      the total weight of type-2 edges within each subgraph. We have developed a
      dynamic programming algorithm for rigorously solving this graph partition problem
      and implemented it as a computer program PRIME. We have tested PRIME on 18 data
      sets of high accurate FT-ICR tandem mass spectra and found that it achieved ~90%
      accuracy for separation of b- and y- ions.

PMID- 16448018
TI  - Multiple RNA structure alignment.
AB  - RNA structures can be viewed as a kind of special strings with some characters
      bonded with each other. The question of aligning two RNA structures has been
      studied for a while, and there are several successful algorithms that are based
      upon different models. In this paper, by adopting the model introduced in [18],
      we propose two algorithms to attack the question of aligning multiple RNA
      structures. We reduce the multiple RNA structure alignment problem to the problem
      of aligning two RNA structure alignments.

PMID- 16448019
TI  - Weighting features to recognize 3D patterns of electron density in X-ray protein
      crystallography.
AB  - Feature selection and weighting are central problems in pattern recognition and
      instance-based learning. In this work, we discuss the challenges of constructing
      and weighting features to recognize 3D patterns of electron density to determine
      protein structures. We present SLIDER, a feature-weighting algorithm that adjusts
      weights iteratively such that patterns that match query instances are better
      ranked than mismatching ones. Moreover, SLIDER makes judicious choices of weight
      values to be considered in each iteration, by examining specific weights at which
      matching and mismatching patterns switch as nearest neighbors to query instances.
      This approach reduces the space of weight vectors to be searched. We make the
      following two main observations: (1) SLIDER efficiently generates weights that
      contribute significantly in the retrieval of matching electron density patterns;
      (2) the optimum weight vector is sensitive to the distance metric i.e. feature
      relevance can be, to a certain extent, sensitive to the underlying metric used to
      compare patterns.

PMID- 16448020
TI  - Reasoning about molecular similarity and properties.
AB  - Ascertaining the similarity amongst molecules is a fundamental problem in biology
      and drug discovery. Since similar molecules tend to have similar biological
      properties, the notion of molecular similarity plays an important role in
      exploration of molecular structural space, query-retrieval in molecular
      databases, and in structure-activity modeling. This problem is related to the
      issue of molecular representation. Currently, approaches with high descriptive
      power like 3D surface-based representations are available. However, most
      techniques tend to focus on 2D graph-based molecular similarity due to the
      complexity that accompanies reasoning with more elaborate representations. This
      paper addresses the problem of determining similarity when molecules are
      described using complex surface-based representations. It proposes an intrinsic,
      spherical representation that systematically maps points on a molecular surface
      to points on a standard coordinate system (a sphere). Molecular geometry,
      molecular fields, and effects due to field super-positioning can then be captured
      as distributions on the surface of the sphere. Molecular similarity is obtained
      by computing the similarity of the corresponding property distributions using a
      novel formulation of histogram-intersection. This method is robust to noise,
      obviates molecular pose-optimization, can incorporate conformational variations,
      and facilitates highly efficient determination of similarity. Retrieval
      performance, applications in structure-activity modeling of complex biological
      properties, and comparisons with existing research and commercial methods
      demonstrate the validity and effectiveness of the approach.

PMID- 16448021
TI  - High-throughput 3D structural homology detection via NMR resonance assignment.
AB  - One goal of the structural genomics initiative is the identification of new
      protein folds. Sequence-based structural homology prediction methods are an
      important means for prioritizing unknown proteins for structure determination.
      However, an important challenge remains: two highly dissimilar sequences can have
      similar folds & how can we detect this rapidly, in the context of structural
      genomics? High-throughput NMR experiments, coupled with novel algorithms for data
      analysis, can address this challenge. We report an automated procedure, called
      HD, for detecting 3D structural homologies from sparse, unassigned protein NMR
      data. Our method identifies 3D models in a protein structural database whose
      geometries best fit the unassigned experimental NMR data. HD does not use, and is
      thus not limited by sequence homology. The method can also be used to confirm or
      refute structural predictions made by other techniques such as protein threading
      or homology modelling. The algorithm runs in O(pn + pn(5/2) log (cn)+p log p)
      time, where p is the number of proteins in the database, n is the number of
      residues in the target protein and c is the maximum edge weight in an integer
      weighted bipartite graph. Our experiments on real NMR data from 3 different
      proteins against a database of 4,500 representative folds demonstrate that the
      method identifies closely related protein folds, including sub-domains of larger
      proteins, with as little as 10-30% sequence homology between the target protein
      (or sub-domain) and the computed model. In particular, we report no false
      negatives or false-positives despite significant percentages of missing
      experimental data.

PMID- 16448023
TI  - An algorithm for detecting homologues of known structured RNAs in genomes.
AB  - Distinct RNA structures are frequently involved in a wide-range of functions in
      various biological mechanisms. The three dimensional RNA structures solved by X
      ray crystallography and various well-established RNA phylogenetic structures
      indicate that functional RNAs have characteristic RNA structural motifs
      represented by specific combinations of base pairings and conserved nucleotides
      in the loop region. Discovery of well-ordered RNA structures and their homologues
      in genome-wide searches will enhance our ability to detect the RNA structural
      motifs and help us to highlight their association with functional and regulatory
      RNA elements. We present here a novel computer algorithm, HomoStRscan, that takes
      a single RNA sequence with its secondary structure to search for homologous-RNAs
      in complete genomes. This novel algorithm completely differs from other currently
      used search algorithms of homologous structures or structural motifs. For an
      arbitrary segment (or window) given in the target sequence, that has similar size
      to the query sequence, HomoStRscan finds the most similar structure to the input
      query structure and computes the maximal similarity score (MSS) between the two
      structures. The homologousRNA structures are then statistically inferred from the
      MSS distribution computed in the target genome. The method provides a flexible,
      robust and fine search tool for any homologous structural RNAs.

PMID- 16448022
TI  - Pair stochastic tree adjoining grammars for aligning and predicting pseudoknot
      RNA structures.
AB  - MOTIVATION: Since the whole genome sequences for many species are currently
      available, computational predictions of RNA secondary structures and
      computational identifications of those non-coding RNA regions by comparative
      genomics become important, and require more advanced alignment methods. Recently,
      an approach of structural alignments for RNA sequences has been introduced to
      solve these problems. By structural alignments, we mean a pairwise alignment to
      align an unfolded RNA sequence into a folded RNA sequence of known secondary
      structure. Pair HMMs on tree structures (PHMMTSs) proposed by Sakakibara are
      efficient automata-theoretic models for structural alignments of RNA secondary
      structures, but are incapable of handling pseudoknots. On the other hand, tree
      adjoining grammars (TAGs) is a subclass of context-sensitive grammar, which is
      suitable for modeling pseudoknots. Our goal is to extend PHMMTSs by incorporating
      TAGs to be able to handle pseudoknots. RESULTS: We propose the pair stochastic
      tree adjoining grammars (PSTAGs) for modeling RNA secondary structures including
      pseudoknots and show the strong experimental evidences that modeling pseudoknot
      structures significantly improves the prediction accuracies of RNA secondary
      structures. First, we extend the notion of PHMMTSs defined on alignments of
      'trees' to PSTAGs defined on alignments of "TAG (derivation) trees", which
      represent a top-down parsing process of TAGs and are functionally equivalent to
      derived trees of TAGs. Second, we modify PSTAGs so that it takes as input a pair
      of a linear sequence and a TAG tree representing a pseudoknot structure of RNA to
      produce a structural alignment. Then, we develop a polynomial-time algorithm for
      obtaining an optimal structural alignment by PSTAGs, based on dynamic programming
      parser. We have done several computational experiments for predicting pseudoknots
      by PSTAGs, and our computational experiments suggests that prediction of RNA
      pseudoknot structures by our method are more efficient and biologically plausible
      than by other conventional methods. The binary code for PSTAG method is freely
      available from our website at http://www.dna.bio.keio.ac.jp/pstag/.

PMID- 16448024
TI  - Inverse protein folding in 2D HP mode (extended abstract).
AB  - The inverse protein folding problem is that of designing an amino acid sequence
      which has a particular native protein fold. This problem arises in drug design
      where a particular structure is necessary to ensure proper protein-protein
      interactions. In this paper we show that in the 2D HP model of Dill it is
      possible to solve this problem for a broad class of structures. These structures
      can be used to closely approximate any given structure. One of the most important
      properties of a good protein is its stability -- the aptitude not to fold
      simultanously into other structures. We show that for a number of basic
      structures, our sequences have a unique fold.

PMID- 16448025
TI  - Analysis of a systematic search-based algorithm for determining protein backbone
      structure from a minimum number of residual dipolar couplings.
AB  - We have developed an ab initio algorithm for determining a protein backbone
      structure using global orientational restraints on internuclear vectors derived
      from residual dipolar couplings (RDCs) measured in one or two different aligning
      media by solution nuclear magnetic resonance (NMR) spectroscopy [14, 15].
      Specifically, the conformation and global orientations of individual secondary
      structure elements are computed, independently, by an exact solution, systematic
      search-based minimization algorithm using only 2 RDCs per residue. The systematic
      search is built upon a quartic equation for computing, exactly and in constant
      time, the directions of an internuclear vector from RDCs, and linear or quadratic
      equations for computing the sines and cosines of backbone dihedral (phi, psi)
      angles from two vectors in consecutive peptide planes. In contrast to heuristic
      search such as simulated annealing (SA) or Monte-Carlo (MC) used by other NMR
      structure determination algorithms, our minimization algorithm can be analyzed
      rigorously in terms of expected algorithmic complexity and the coordinate
      precision of the protein structure as a function of error in the input data. The
      algorithm has been successfully applied to compute the backbone structures of
      three proteins using real NMR data.

PMID- 16448026
TI  - Multi-knockout genetic network analysis: the Rad6 example.
AB  - A novel and rigorous Multi-perturbation Shapley Value Analysis (MSA) method has
      been recently presented [12]. The method addresses the challenge of defining and
      calculating the functional causal contributions of elements of a biological
      system. This paper presents the first study applying MSA to the analysis of gene
      knockout data. The MSA identifies the importance of genes in the Rad6 DNA repair
      pathway of the yeast S. cerevisiae, quantifying their contributions and
      characterizing their functional interactions. Incorporating additional biological
      knowledge, a new functional description of the Rad6 pathway is provided,
      predicting the existence of additional DNA polymerase and RFC-like complexes. The
      MSA is the first method for rigorously analyzing multi-knockout experiments,
      which are likely to soon become a standard and necessary tool for analyzing
      complex biological systems.

PMID- 16448027
TI  - A hierarchical mixture of Markov models for finding biologically active metabolic
      paths using gene expression and protein classes.
AB  - With the recent development of experimental high-throughput techniques, the type
      and volume of accumulating biological data have extremely increased these few
      years. Mining from different types of data might lead us to find new biological
      insights. We present a new methodology for systematically combining three
      different datasets to find biologically active metabolic paths/patterns. This
      method consists of two steps: First it synthesizes metabolic paths from a given
      set of chemical reactions, which are already known and whose enzymes are co
      expressed, in an efficient manner. It then represents the obtained metabolic
      paths in a more comprehensible way through estimating parameters of a
      probabilistic model by using these synthesized paths. This model is built upon an
      assumption that an entire set of chemical reactions corresponds to a Markov state
      transition diagram. Furthermore, this model is a hierarchical latent variable
      model, containing a set of protein classes as a latent variable, for clustering
      input paths in terms of existing knowledge of protein classes. We tested the
      performance of our method using a main pathway of glycolysis, and found that our
      method achieved higher predictive performance for the issue of classifying gene
      expressions than those obtained by other unsupervised methods. We further
      analyzed the estimated parameters of our probabilistic models, and found that
      biologically active paths were clustered into only two or three patterns for each
      expression experiment type, and each pattern suggested some new long-range
      relations in the glycolysis pathway.

PMID- 16448028
TI  - Dynamic algorithm for inferring qualitative models of gene regulatory networks.
AB  - It is still an open problem to identify functional relations with o(N . n(k))
      time for any domain[2], where N is the number of learning instances, n is the
      number of genes (or variables) in the Gene Regulatory Network (GRN) models and k
      is the indegree of the genes. To solve the problem, we introduce a novel
      algorithm, DFL (Discrete Function Learning), for reconstructing qualitative
      models of GRNs from gene expression data in this paper. We analyze its complexity
      of O(k . N . n(2)) on the average and its data requirements. We also perform
      experiments on both synthetic and Cho et al. [7] yeast cell cycle gene expression
      data to validate the efficiency and prediction performance of the DFL algorithm.
      The experiments of synthetic Boolean networks show that the DFL algorithm is more
      efficient than current algorithms without loss of prediction performances. The
      results of yeast cell cycle gene expression data show that the DFL algorithm can
      identify biologically significant models with reasonable accuracy, sensitivity
      and high precision with respect to the literature evidences. We further introduce
      a method called epsilon function to deal with noises in data sets. The
      experimental results show that the epsilon function method is a good supplement
      to the DFL algorithm.

PMID- 16448029
TI  - Mapping of microbial pathways through constrained mapping of orthologous genes.
AB  - We present a novel computer algorithm for mapping biological pathways from one
      prokaryotic genome to another. The algorithm maps genes in a known pathway to
      their homologous genes (if any) in a target genome that is most consistent with
      (a) predicted orthologous gene relationship, (b) predicted operon structures, and
      (c) predicted co-regulation relationship of operons. Mathematically, we have
      formulated this problem as a constrained minimum spanning tree problem (called a
      Steiner network problem), and demonstrated that this formulation has the desired
      property through applications. We have solved this mapping problem using a
      combinatorial optimization algorithm, with guaranteed global optimality. We have
      implemented this algorithm as a computer program, called PMAP. Our test results
      on pathway mapping are highly encouraging -- we have mapped a number of pathways
      of H. influenzae, B. subtilis, H. pylori, and M. tuberculosis to E. coli using P
      MAP, whose homologous pathways in E coli. are known and hence the mapping
      accuracy could be checked. We have then mapped known E. coli pathways in the
      EcoCyc database to the newly sequenced organism Synechococcus sp WH8102, and
      predicted 158 Synechococcus pathways. Detailed analyses on the predicted pathways
      indicate that P-MAP's mapping results are consistent with our general knowledge
      about (local) pathways. We believe that P-MAP will be a useful tool for microbial
      genome annotation projects and inference of individual microbial pathways.

PMID- 16448030
TI  - PoPS: a computational tool for modeling and predicting protease specificity.
AB  - Proteases play a fundamental role in the control of intra- and extracellular
      processes by binding and cleaving specific amino acid sequences. Identifying
      these targets is extremely challenging. Current computational attempts to predict
      cleavage sites are limited, representing these amino acid sequences as patterns
      or frequency matrices. Here we present PoPS, a publicly accessible bioinformatics
      tool (http://pops.csse.monash.edu.au/) which provides a novel method for building
      computational models of protease specificity that, while still being based on
      these amino acid sequences, can be built from any experimental data or expert
      knowledge available to the user. PoPS specificity models can be used to predict
      and rank likely cleavages within a single substrate, and within entire proteomes.
      Other factors, such as the secondary or tertiary structure of the substrate, can
      be used to screen unlikely sites. Furthermore, the tool also provides facilities
      to infer, compare and test models, and to store them in a publicly accessible
      database.

PMID- 16448031
TI  - Selection of patient samples and genes for outcome prediction.
AB  - Gene expression profiles with clinical outcome data enable monitoring of disease
      progression and prediction of patient survival at the molecular level. We present
      a new computational method for outcome prediction. Our idea is to use an
      informative subset of original training samples. This subset consists of only
      short-term survivors who died within a short period and long-term survivors who
      were still alive after a long follow-up time. These extreme training samples
      yield a clear platform to identify genes whose expression is related to survival.
      To find relevant genes, we combine two feature selection methods -- entropy
      measure and Wilcoxon rank sum test -- so that a set of sharp discriminating
      features are identified. The selected training samples and genes are then
      integrated by a support vector machine to build a prediction model, by which each
      validation sample is assigned a survival/relapse risk score for drawing Kaplan
      Meier survival curves. We apply this method to two data sets: diffuse large-B
      cell lymphoma (DLBCL) and primary lung adenocarcinoma. In both cases, patients in
      high and low risk groups stratified by our risk scores are clearly
      distinguishable. We also compare our risk scores to some clinical factors, such
      as International Prognostic Index score for DLBCL analysis and tumor stage
      information for lung adenocarcinoma. Our results indicate that gene expression
      profiles combined with carefully chosen learning algorithms can predict patient
      survival for certain diseases.

PMID- 16448032
TI  - Comparison of two schemes for automatic keyword extraction from MEDLINE for
      functional gene clustering.
AB  - One of the key challenges of microarray studies is to derive biological insights
      from the unprecedented quatities of data on gene-expression patterns. Clustering
      genes by functional keyword association can provide direct information about the
      nature of the functional links among genes within the derived clusters. However,
      the quality of the keyword lists extracted from biomedical literature for each
      gene significantly affects the clustering results. We extracted keywords from
      MEDLINE that describes the most prominent functions of the genes, and used the
      resulting weights of the keywords as feature vectors for gene clustering. By
      analyzing the resulting cluster quality, we compared two keyword weighting
      schemes: normalized z-score and term frequency-inverse document frequency
      (TFIDF). The best combination of background comparison set, stop list and
      stemming algorithm was selected based on precision and recall metrics. In a test
      set of four known gene groups, a hierarchical algorithm correctly assigned 25 of
      26 genes to the appropriate clusters based on keywords extracted by the TDFIDF
      weighting scheme, but only 23 og 26 with the z-score method. To evaluate the
      effectiveness of the weighting schemes for keyword extraction for gene clusters
      from microarray profiles, 44 yeast genes that are differentially expressed during
      the cell cycle were used as a second test set. Using established measures of
      cluster quality, the results produced from TFIDF-weighted keywords had higher
      purity, lower entropy, and higher mutual information than those produced from
      normalized z-score weighted keywords. The optimized algorithms should be useful
      for sorting genes from microarray lists into functionally discrete clusters.

PMID- 16448033
TI  - Calculation, visualization, and manipulation of MASTs (Maximum Agreement
      Subtrees).
AB  - Phylogenetic trees are used to represent the evolutionary history of a set of
      species. Comparison of multiple phylogenetic trees can help researchers find the
      common classification of a tree group, compare tree construction inferences or
      obtain distances between trees. We present TreeAnalyzer, a freely available
      package for phylogenetic tree comparison. A MAST (Maximum Agreement Subtree)
      algorithm is implemented to compare the trees. Additional features of this
      software include tree comparison, visualization, manipulation, labeling, and
      printing. AVAILABILITY: http://www.cs.uga.edu/~eileen/TreeAnalyzer.

PMID- 16448034
TI  - AZuRE, a scalable system for automated term disambiguation of gene and protein
      names.
AB  - Researchers, hindered by a lack of standard gene and protein-naming conventions,
      endure long, sometimes fruitless, literature searches. A system is described
      which is able to automatically assign gene names to their LocusLink ID (LLID) in
      previously unseen MEDLINE abstracts. The system is based on supervised learning
      and builds a model for each LLID. The training sets for all LLIDs are extracted
      automatically from MEDLINE references in the LocusLink and SwissProt databases. A
      validation was done of the performance for all 20,546 human genes with LLIDs. Of
      these, 7,344 produced good quality models (F-measure > 0.7, nearly 60% of which
      were > 0.9) and 13,202 did not, mainly due to insufficient numbers of known
      document references. A hand validation of MEDLINE documents for a set of 66 genes
      agreed well with the system's internal accuracy assessment. It is concluded that
      it is possible to achieve high quality gene disambiguation using scaleable
      automated techniques.

PMID- 16448035
TI  - Comparative analysis of gene sets in the Gene Ontology space under the multiple
      hypothesis testing framework.
AB  - The Gene Ontology (GO) resource can be used as a powerful tool to uncover the
      properties shared among, and specific to, a list of genes produced by high
      throughput functional genomics studies, such as microarray studies. In the
      comparative analysis of several gene lists, researchers maybe interested in
      knowing which GO terms are enriched in one list of genes but relatively depleted
      in another. Statistical tests such as Fisher's exact test or Chi-square test can
      be performed to search for such GO terms. However, because multiple GO terms are
      tested simultaneously, individual p-values from individual tests do not serve as
      good indicators for picking GO terms. Furthermore, these multiple tests are
      highly correlated, usual multiple testing procedures that work under an
      independence assumption are not applicable. In this paper we introduce a
      procedure, based on False Discovery Rate (FDR), to treat this correlated multiple
      testing problem. This procedure calculates a moderately conserved estimator of q
      value for every GO term. We identify the GO terms with q-values that satisfy a
      desired level as the significant GO terms. This procedure has been implemented
      into the GoSurfer software. GoSurfer is a windows based graphical data mining
      tool. It is freely available at http://www.gosurfer.org.

PMID- 16448036
TI  - Gene Ontology friendly biclustering of expression profiles.
AB  - The soundness of clustering in the analysis of gene expression profiles and gene
      function prediction is based on the hypothesis that genes with similar expression
      profiles may imply strong correlations with their functions in the biological
      activities. Gene Ontology (GO) has become a well accepted standard in organizing
      gene function categories. Different gene function categories in GO can have very
      sophisticated relationships, such as 'part of' and 'overlapping'. Until now, no
      clustering algorithm can generate gene clusters within which the relationships
      can naturally reflect those of gene function categories in the GO hierarchy. The
      failure in resembling the relationships may reduce the confidence of clustering
      in gene function prediction. In this paper, we present a new clustering
      technique, Smart Hierarchical Tendency Preserving clustering (SHTP-clustering),
      based on a bicluster model, Tendency Preserving cluster (TP-Cluster). By directly
      incorporating Gene Ontology information into the clustering process, the SHTP
      clustering algorithm yields a TP-cluster tree within which any subtree can be
      well mapped to a part of the GO hierarchy. Our experiments on yeast cell cycle
      data demonstrate that this method is efficient and effective in generating the
      biological relevant TP-Clusters.

PMID- 16448037
TI  - UV fluorescence lifetime imaging microscopy: a label-free method for detection
      and quantification of protein interactions.
AB  - Due to the ability to detect multiple parameters simultaneously, protein
      microarrays have found widespread applications from basic biological research to
      diagnosis of diseases. Generally, readout of protein microarrays is performed by
      fluorescence detection using either dye-labeled detector antibodies or direct
      labeling of the target proteins. We developed a method for the label-free
      detection and quantification of proteins based on time-gated, wide-field, camera
      based UV fluorescence lifetime imaging microscopy to gain lifetime information
      from each pixel of a sensitive CCD camera. The method relies on differences in
      the native fluorescence lifetime of proteins and takes advantage of binding
      induced lifetime changes for the unequivocal detection and quantification of
      target proteins. Since fitting of the fluorescence decay for every pixel in an
      image using a classical exponential decay model is time-consuming and unstable at
      very low fluorescence intensities, we used a new, very robust and fast
      alternative method to generate UV fluorescence lifetime images by calculating the
      average lifetime of the decay for each pixel in the image stack using a model
      free average decay time algorithm.To validate the method, we demonstrate the
      detection and quantification of p53 antibodies, a tumor marker in cancer
      diagnosis. Using tryptophan-containing capture peptides, we achieved a detection
      sensitivity for monoclonal antibodies down to the picomolar concentration range.
      The obtained affinity constant, Ka, of (1.4 +/- 0.6) x 10(9) M(-1), represents a
      typical value for antigen/antibody binding and is in agreement with values
      determined by traditional binding assays.

PMID- 16448038
TI  - Differentiation of isomers by wavelength-tunable infrared multiple-photon
      dissociation-mass spectrometry: application to glucose-containing disaccharides.
AB  - Variation in the wavelength of irradiation in infrared multiple-photon
      dissociation (IR-MPD) of lithium-tagged glucose-containing disaccharide ions (1-2
      , 1-3-, 1-4-, and 1-6-linked isomers of both anomeric configurations) resulted in
      marked differences in their mass spectral fragmentation patterns. Two-dimensional
      plots of the fragment yield versus infrared wavelength for each mass spectral
      product ion were unique for each isomer and can be considered a spectral
      fingerprint. Individual product ions or diagnostic ratios of key product ions can
      be optimized at specific IR wavelengths. The technique permits both linkage
      position and anomeric configuration to be assigned. The ratio of the fragments
      derived by cleavage at the glycosidic bond (m/z 169/187) is much enhanced for
      beta-anomers compared to alpha-anomers. Differences in the diagnostic product
      ions 169 and 187 were largest in the range of 9.0-9.4 microm, where the maximum
      dissociation yield was observed. Conversely, at 10.6 microm, the wavelength of
      nontunable CO2 lasers that accompany commercial Fourier transform ion cyclotron
      resonance mass spectrometers, the dissociation yield was poor and anomeric
      differentiation was not possible. In contrast to previous studies by collision
      induced dissociation, the trends in dissociation behavior between anomers using
      IR-MPD are significant and allow simple diagnostic rules to be established. By
      depositing energy into these isobaric ions via narrow-band IR excitation, the
      resulting internal energy can be finely controlled, thereby obtaining high
      reproducibility in dissociation patterns. Given the multidimensionality of
      variable-wavelength IR-MPD of lithiated disaccharides, it is expected that this
      approach can overcome some of the current limitations in isomer differentiation.

PMID- 16448039
TI  - Remnant lipoprotein density profiling by CsBiEDTA density gradient
      ultracentrifugation.
AB  - Remnant lipoproteins (RLPs) are now considered a strong marker of the
      triglyceride-rich lipoprotein (TRL) class for cardiovascular heart disease. The
      purpose of this research is to demonstrate the efficacy of a novel method that
      combines an established immunoseparation assay used to measure the RLP class in
      human serum with ultracentrifugal density gradient separation. These two methods
      are combined to obtain an RLP density profile. The immunoseparation effectively
      removes the non-RLP lipoproteins from serum. The RLPs obtained from the
      immunoseparation are separated into two density-distinct fractions by
      ultracentrifugal density gradient separation in CsBiEDTA. It is now clear that
      IDL is distinct in density and immunoreactivity from the two RLP classes isolated
      by the immunoseparation and ultracentrifugation. This methodology defines the RLP
      by density and measures their relative prevalence in the TRL class. When applied
      to clinical samples, variations in the RLP subclasses in different patients are
      examined. The differences in the RLP density profile are also examined in fasting
      and postprandial samples. The RLP density profile significantly increases in the
      postprandial state versus the fasting state. However, the overall quantity of TRL
      does not appreciably increase in the postprandial state. This work demonstrates
      the feasibility of measuring the postprandial state in clinical samples to
      provide insight into the clearance of RLP by the liver as well as the general
      atherogenicity of these particles. The major outcome of this research is a novel
      analytical method that couples immunoseparation and density gradient
      ultracentrifugation to separate and differentially profile the RLP subclass
      against its nascent counterparts in the TRL class.

PMID- 16448040
TI  - Top-down approaches for measuring expression ratios of intact yeast proteins
      using Fourier transform mass spectrometry.
AB  - The extension of quantitation methods for small peptides to ions above 5 kDa, and
      eventually to global quantitative proteomics of intact proteins, will require
      extensive refinement of current analytical approaches. Here we evaluate
      postgrowth Cys-labeling and 14N/15N metabolic labeling strategies for
      determination of relative protein expression levels and their posttranslational
      modifications using top-down mass spectrometry (MS). We show that intact proteins
      that are differentially alkylated with acrylamide (+71 Da) versus iodoacetamide
      (+57 Da) have substantial chromatographic shifts during reversed-phase liquid
      chromatography separation (particularly in peak tails), indicating a requirement
      for stable isotopes in alkylation tags for top-down MS. In the 14N/15N metabolic
      labeling strategy, we achieve 98% 15N incorporation in yeast grown 10 generations
      under aerobic conditions and determine 50 expression ratios using Fourier
      transform ion cyclotron resonance MS in comparing these cells to anaerobically
      grown control (14N) cells. We devise quantitative methods for top-down analyses,
      including a correction factor for accurate protein ratio determination based upon
      the signal-to-noise ratio. Using a database of 200 yeast protein forms identified
      previously by top-down MS, we verify the intact mass tag concept for protein
      identification without tandem MS. Overall, we find that top-down MS promises work
      flows capable of large-scale proteome profiling using stable isotope labeling and
      the determination of >5 protein ratios per spectrum.

PMID- 16448041
TI  - On-chip cell sorting system using laser-induced heating of a thermoreversible
      gelation polymer to control flow.
AB  - We have developed a microfabricated fluorescence-activated cell sorter system
      using a thermoreversible gelation polymer (TGP) as a switching valve. The glass
      sorter chip has Y-shaped microchannels with one inlet and two outlets. A
      biological specimen containing fluorescently labeled cells is mixed with a
      solution containing a thermoreversible sol-gel polymer. The mixed solution is
      then introduced into the sorter chip through the inlet. The sol-gel
      transformation was locally induced by site-directed infrared laser irradiation to
      plug one of the outlets. The fluorescently labeled target cells were detected
      with sensitive fluorescence microscopy. In the absence of a fluorescence signal,
      the collection channel is plugged through laser irradiation of the TGP and the
      specimens are directed to the waste channel. Upon detection of a fluorescence
      signal from the target cells, the laser beam is then used to plug the waste
      channel, allowing the fluorescent cells to be channeled into the collection
      reservoir. The response time of the sol-gel transformation was 3 ms, and a flow
      switching time of 120 ms was achieved. Using this system, we have demonstrated
      the sorting of fluorescent microspheres and Escherichia coli cells expressing
      fluorescent proteins. These cells were found to be viable after extraction from
      the sorting system, indicating no damage to the cells.

PMID- 16448042
TI  - Differential phosphoprotein mapping in cancer cells using protein microarrays
      produced from 2-D liquid fractionation.
AB  - A combination of protein microarrays and two-dimensional liquid-phase separation
      of proteins has been used for global profiling of the phosphoproteome in human
      breast cancer cells. This method has been applied to study changes in
      phosphorylation profile resulting from treatment of the cancer cells with
      PD173074, a known receptor tyrosine kinase inhibitor. The proteins separated by 2
      D liquid-phase separation were arrayed on epoxy-coated glass slides and first
      screened for phosphorylation using fluorescent Pro-Q Diamond stain. The candidate
      proteins were then identified using MALDI/ESI MS/MS analysis. Further, validation
      was achieved by immunoblot analysis using anti-phosphotyrosine antibodies. A
      dynamic range of approximately 100 was achieved on the microarray when beta
      casein was used as a standard protein for obtaining quantitative data.
      Importantly, the power of this method lies in its ability to identify a large
      group of proteins in a single experiment that are coregulated in their
      posttranslational modifications, upon treatment with the inhibitor. Since
      proteins are known to form interacting circuits that eventually lead to various
      signaling events, detection of such global phosphorylation profiles might enable
      delineation of functional pathways that play an important role during cancer
      initiation and progression.

PMID- 16448043
TI  - Dynamic, electronically switchable surfaces for membrane protein microarrays.
AB  - Microarray technology is a powerful tool that provides a high throughput of
      bioanalytical information within a single experiment. These miniaturized and
      parallelized binding assays are highly sensitive and have found widespread
      popularity especially during the genomic era. However, as drug diagnostics
      studies are often targeted at membrane proteins, the current arraying
      technologies are ill-equipped to handle the fragile nature of the protein
      molecules. In addition, to understand the complex structure and functions of
      proteins, different strategies to immobilize the probe molecules selectively onto
      a platform for protein microarray are required. We propose a novel approach to
      create a (membrane) protein microarray by using an indium tin oxide (ITO)
      microelectrode array with an electronic multiplexing capability. A polycationic,
      protein- and vesicle-resistant copolymer, poly(l-lysine)-grafted-poly(ethylene
      glycol) (PLL-g-PEG), is exposed to and adsorbed uniformly onto the microelectrode
      array, as a passivating adlayer. An electronic stimulation is then applied onto
      the individual ITO microelectrodes resulting in the localized release of the
      polymer thus revealing a bare ITO surface. Different polymer and biological
      moieties are specifically immobilized onto the activated ITO microelectrodes
      while the other regions remain protein-resistant as they are unaffected by the
      induced electrical potential. The desorption process of the PLL-g-PEG is observed
      to be highly selective, rapid, and reversible without compromising on the
      integrity and performance of the conductive ITO microelectrodes. As such, we have
      successfully created a stable and heterogeneous microarray of biomolecules by
      using selective electronic addressing on ITO microelectrodes. Both pharmaceutical
      diagnostics and biomedical technology are expected to benefit directly from this
      unique method.

PMID- 16448044
TI  - Rectilinear ion trap mass spectrometer with atmospheric pressure interface and
      electrospray ionization source.
AB  - A rectilinear ion trap (RIT) mass analyzer was incorporated into a mass
      spectrometer fitted with an electrospray ionization source and an atmospheric
      pressure interface. The RIT mass spectrometer, which was assembled in two
      different configurations, was used for the study of biological compounds, for
      which performance data are given. A variety of techniques, including the use of a
      balanced rf, elevated background gas pressure, automatic gain control, and
      resonance ejection waveforms with dynamically adjusted amplitude, were applied to
      enhance performance. The capabilities of the instrument were characterized using
      proteins, peptides, and pharmaceutical drugs. Unit resolution and an accuracy of
      better than m/z 0.2 was achieved for mass-to-charge (m/z) ratios up to 2000 Th at
      a scan rate of approximately 3000 amu/(charge.s) while reduced scan rates gave
      greater resolution and peak widths of less than m/z 0.5 over the same range. The
      mass discrimination in trapping externally generated ions was characterized over
      the range m/z 190-2000 and an optimized low mass cutoff value of m/z 120-140 was
      found to give equal trapping efficiencies over the entire range. The radial
      detection efficiency was measured as a function of m/z ratio and found to rise
      from 35% at low m/z values to more than 90% for ions of m/z 1800. The way in
      which the ion trapping capacity depends on the dc trapping potential was
      investigated by measuring the mass shift due to space charge effects, and it was
      shown that low trapping potentials minimize space charge effects by increasing
      the useful volume of the device. The collision-induced dissociation (CID)
      capabilities of the RIT instrument were evaluated by measuring isolation
      efficiency as a function of mass resolution as well as measuring peptide CID
      efficiencies. Overall CID efficiencies of more than 60% were easily reached,
      while isolation of an ion with unit resolution at m/z 524 was achieved with high
      rejection (>95%) of the adjacent ions. The overall analytical capabilities of the
      ESI-RIT instrument were demonstrated with the analysis of a mixture of
      pharmaceutical compounds using multiple-stage mass spectrometry.

PMID- 16448045
TI  - Scanning electrochemical microscopy. 56. Probing outside and inside single giant
      liposomes containing Ru(bpy)32+.
AB  - Giant liposomes containing Ru(bpy)(3)(2+) (bpy = 2,2'-bipyridine) were prepared
      as model systems for biomembranes and cells and studied by scanning
      electrochemical microscopy (SECM). Conical carbon fiber tips of submicrometer
      size were used to approach, image, and puncture individual liposomes immobilized
      on glass substrates. SECM images of the liposomes were obtained, and the leakage
      of Ru(bpy)(3)(2+) through the lipid membrane was probed. The tip was also pushed
      into liposomes and characteristic breakthrough transients, corresponding to
      liposomes with different compartmental configurations, were obtained.
      Voltammograms were obtained with the tip inside a single liposome after breaking
      through the membrane, and the influx of mediator and efflux of encapsulant after
      puncture could be observed.

PMID- 16448046
TI  - Gold-enhanced biomolecular surface imaging of cells and tissue by SIMS and MALDI
      mass spectrometry.
AB  - Surface metallization by plasma coating enhances desorption/ionization of
      membrane components such as lipids and sterols in imaging time-of-flight
      secondary ion mass spectrometry (TOF-SIMS) of tissues and cells. High-resolution
      images of cholesterol and other membrane components were obtained for
      neuroblastoma cells and revealed subcellular details (resolving power 1.5 mum).
      Alternatively, in matrix-enhanced SIMS, 2,5-dihydroxybenzoic acid electrosprayed
      on neuroblastoma cells allowed intact molecular ion imaging of
      phosphatidylcholine and sphingomyelin at the cellular level. Gold deposition on
      top of matrix-coated rat brain tissue sections strongly enhanced image quality
      and signal intensity in stigmatic matrix-assisted laser desorption/ionization
      imaging mass spectrometry. High-quality total ion count images were acquired, and
      the neuropeptide vasopressin was localized in the rat brain tissue section at the
      hypothalamic area around the third ventricle. Although the mechanism of signal
      enhancement by gold deposition is under debate, the results we have obtained for
      cells and tissue sections illustrate the potential of this sample preparation
      technique for biomolecular surface imaging by mass spectrometry.

PMID- 16448047
TI  - Solvent-dependent metabolite distribution, clustering, and protein extraction for
      serum profiling with mass spectrometry.
AB  - The aim of metabolite profiling is to monitor all metabolites within a biological
      sample for applications in basic biochemical research as well as pharmacokinetic
      studies and biomarker discovery. Here, novel data analysis software, XCMS, was
      used to monitor all metabolite features detected from an array of serum
      extraction methods, with application to metabolite profiling using electrospray
      liquid chromatography/mass spectrometry (ESI-LC/MS). The XCMS software enabled
      the comparison of methods with regard to reproducibility, the number and type of
      metabolite features detected, and the similarity of these features between
      different extraction methods. Extraction efficiency with regard to metabolite
      feature hydrophobicity was examined through the generation of unique feature
      density distribution plots, displaying feature distribution along chromatographic
      time. Hierarchical clustering was performed to highlight similarities in the
      metabolite features observed between the extraction methods. Protein extraction
      efficiency was determined using the Bradford assay, and the residual proteins
      were identified using nano-LC/MS/MS. Additionally, the identification of four of
      the most intensely ionized serum metabolites using FTMS and tandem mass
      spectrometry was reported. The extraction methods, ranging from organic solvents
      and acids to heat denaturation, varied widely in both protein removal efficiency
      and the number of mass spectral features detected. Methanol protein precipitation
      followed by centrifugation was found to be the most effective, straightforward,
      and reproducible approach, resulting in serum extracts containing over 2000
      detected metabolite features and less than 2% residual protein. Interestingly,
      the combination of all approaches produced over 10,000 unique metabolite
      features, a number that is indicative of the complexity of the human metabolome
      and the potential of metabolomics in biomarker discovery.

PMID- 16448048
TI  - Chemiresistive vapor sensing with microscale films of gold monolayer protected
      clusters.
AB  - Here we report the stability, conductivity, and vapor-sensing properties of
      microcontact-printed films of 1.6-nm average diameter hexanethiolate-coated gold
      monolayer protected clusters (C6 Au MPCs). The C6 Au MPCs were stamped into
      parallel lines (approximately 1.2 microm wide and 400 nm thick) across two Au
      electrodes separated by a 1-microm gap. The chemiresistive vapor-sensing
      properties were measured for saturated toluene and 2-propanol vapors. As-prepared
      patterned Au MPC films were unstable in the presence of saturated toluene vapor,
      and their current response was irreversible. Chemically linking the films with
      vapor-phase hexanedithiol greatly improves their stability and leads to
      reversible responses. The extent of Au MPC cross-linking and vapor response to
      organic vapors varies with different exposure times to dithiol vapor. The
      response to toluene changed from 61 to 8% for exposures of 1 and 60 min,
      respectively, which is likely due to greater film flexibility with less dithiol
      exposure. The current measured through the films varies from 10(-11) to 10(-3)
      Angstroms as a function of the temperature between 250 and 320 degrees C, which
      correlates with the loss of organic material as measured by FT-IR spectroscopy
      and the change in thickness and width of the film as measured by atomic force
      microscopy. The vapor-sensing properties vary with temperature, current, and
      organic content in the film, which are all interrelated. Response to toluene
      decreased with increasing temperature and conductivity, while the response to 2
      propanol was less predictable. Reducing the size of vapor-sensing devices based
      on Au MPCs is important for creating highly portable devices that can
      simultaneously detect multiple analytes. This work demonstrates a simple method
      for reducing the size of such devices down to the microscale and describes
      methods for maximizing response, stability, and reversibility.

PMID- 16448049
TI  - Electrochemical determination of arsenite using a gold nanoparticle modified
      glassy carbon electrode and flow analysis.
AB  - A flow analysis electrochemical system has been developed, characterized, and
      optimized for the determination of arsenite (As(III)). Sensitivity was
      significantly improved by the electrochemical deposition of gold nanoparticles on
      a dual glassy carbon electrode, which was inserted into a cross-flow thin-layer
      electrochemical cell. The electrochemical system was linear up to 15 ppb with a
      detection limit of 0.25 ppb. Gold deposition was evident from cyclic voltammetry
      measurements, whereas atomic force microscopy and scanning electron microscopy
      revealed the size and distribution of deposited gold nanoparticles. The size and
      density of the nanoparticles were related to the gold salt concentration,
      deposition time, and potential as well as the electrode position. The response to
      arsenite was directly related to the frequency, increment, and amplitude of the
      square wave voltammetry as well as the deposition time and potential. Estimated
      reproducibility was +/-1.1% at 95% confidence interval for 40 repeated analyses
      of 8 ppb arsenite during continuous analysis. The reproducibility was far
      superior if the electrochemical reduction of arsenite was performed in nitric
      acid instead of hydrochloric or sulfuric acid. The electrochemical system was
      applicable for analysis of spiked arsenic in mineral water containing a
      significant amount of various ion elements.

PMID- 16448050
TI  - Enrichment of carbonylated peptides using Girard P reagent and strong cation
      exchange chromatography.
AB  - It has been shown that oxidatively modified forms of proteins accumulate during
      oxidative stress, aging, and in some age-related diseases. One of the unique
      features of protein oxidation by a wide variety of routes is the generation of
      carbonyl groups. Of major interest in the study of oxidative stress diseases is
      which proteins in a proteome are being oxidized and the site(s) of oxidation.
      Based on the fact that proteins are generally characterized through tryptic
      peptide fragments, this paper reports a method for the isolation of oxidized
      peptides, which involves (1) derivatization of oxidized proteins with Girard P
      reagent (GRP; 1-(2-hydrazino-2-oxoethyl)pyridinium chloride), (2) following
      proteolysis enrichment of the derivatized peptide using strong cation exchange
      (SCX) chromatography, and (3) identification of oxidation sites using tandem mass
      spectrometry. Derivatization of aldehydes and ketones in oxidized proteins was
      accomplished by reacting protein carbonyls with the hydrazide of GRP. The
      resulting hydrazone bond was reduced by sodium cyanoborohydride to further
      stabilize the labeling. Derivatization time and concentrations of the
      derivatizing agent were optimized with model peptides. Oxidized transferrin was
      used as model protein to study derivatization efficiency at the protein level.
      Following metal-catalyzed oxidation of transferrin, the protein was derivatized
      with GRP and trypsin digested. Positively charged peptides were then selected
      from the digest with SCX chromatography at pH 6.0. Seven GRP-derivatized peptides
      were found to be selected from transferrin by MALDI-TOF-TOF analysis. Fourteen
      underivatized native peptides were also captured by the SCX column at pH 6.0.
      Mapping of the derivatized peptides onto the primary structure of transferrin
      indicated that the oxidation sites were all on solvent-accessible regions at the
      protein surface. Efficiency of the method was further demonstrated in the
      identification of oxidized proteins from yeast.

PMID- 16448051
TI  - XCMS: processing mass spectrometry data for metabolite profiling using nonlinear
      peak alignment, matching, and identification.
AB  - Metabolite profiling in biomarker discovery, enzyme substrate assignment, drug
      activity/specificity determination, and basic metabolic research requires new
      data preprocessing approaches to correlate specific metabolites to their
      biological origin. Here we introduce an LC/MS-based data analysis approach, XCMS,
      which incorporates novel nonlinear retention time alignment, matched filtration,
      peak detection, and peak matching. Without using internal standards, the method
      dynamically identifies hundreds of endogenous metabolites for use as standards,
      calculating a nonlinear retention time correction profile for each sample.
      Following retention time correction, the relative metabolite ion intensities are
      directly compared to identify changes in specific endogenous metabolites, such as
      potential biomarkers. The software is demonstrated using data sets from a
      previously reported enzyme knockout study and a large-scale study of plasma
      samples. XCMS is freely available under an open-source license at
      http://metlin.scripps.edu/download/.

PMID- 16448052
TI  - Thermoplastic microfluidic device for on-chip purification of nucleic acids for
      disposable diagnostics.
AB  - A polymeric microfluidic device for solid-phase extraction (SPE)-based isolation
      of nucleic acids is demonstrated. The plastic chip can function as a disposable
      sample preparation system for different biological and diagnostic applications.
      The chip was fabricated in a cyclic polyolefin by hot-embossing with a master
      mold. The solid phase consisted of a porous monolithic polymer column impregnated
      with silica particles. The extraction was achieved due to the binding of nucleic
      acids to the silica particles in the monolith. The solid phase was formed within
      the channels of the device by in situ photoinitiated polymerization of a mixture
      of methacrylate and dimethacrylate monomers, UV-sensitive free-radical initiator,
      and porogenic solvents. The channel surfaces were pretreated via photografting to
      covalently attach the monolith to the channel walls. The solid phase prepared by
      this method allowed for successful extraction and elution of nucleic acids in the
      polymeric microchip.

PMID- 16448053
TI  - Plastic ELISA-on-a-chip based on sequential cross-flow chromatography.
AB  - A plastic chip that can perform immunoassays using an enzyme as signal generator,
      i.e., ELISA-on-a-chip, was developed by incorporating an immunostrip into
      channels etched on the surfaces of the chip. To utilize an analytical concept of
      cross-flow chromatography, the chip consisted of two cross-flow channels in the
      horizontal and vertical directions. In the vertical channel, we placed a 2-mm
      wide immunostrip for cardiac troponin I (cTnI), which was identical to a
      conventional rapid test kit except for the utilization of an enzyme, horseradish
      peroxidase (HRP), as tracer. An enzyme substrate supply channel and a horizontal
      flow absorption pad compartment were transversely arranged on each lateral side
      of the signal generation pad of the strip, respectively. Upon application of a
      sample containing cTnI, it migrated vertically through the membrane strip by
      capillary action, and antigen-antibody binding occurred. After 15 min, the
      horizontal flow was initiated by the addition of a chromogenic substrate solution
      for HRP into the supply channel and by partial superimposition of the horizontal
      flow absorption pad onto the signal generation pad. A color signal proportional
      to the analyte concentration was produced on this pad, measured after 5 min as
      optical densities using a digital camera-based detector, and quantified by
      integration of the densities under the peak after normalization. Its calibration
      curve indicated that the detection limit of the chip was approximately 0.1 ng/mL
      and its quantification limit was 0.25 ng/mL. In measuring blindly prepared
      samples, the chip performance correlated with that of a reference system, Beckman
      Coulter Access, within 2.5-fold discrepancy at the detection limit.

PMID- 16448055
TI  - Solid ionic matrixes for direct tissue analysis and MALDI imaging.
AB  - Direct analysis of tissue by MALDI-MS allows the acquisition of its biomolecular
      profile while maintaining the integrity of the tissue, giving cellular
      localization, and avoiding tedious extraction and purification steps. However,
      direct tissue analysis generally leads to some extent to a lowered spectral
      quality due to variation in thickness, freezing tissue date, and nature of the
      tissue. We present here new technical developments for the direct tissue analysis
      of peptides with ionic liquid made of matrix mixtures (alpha-cyano-4
      hydroxycinnamic acid (CHCA)/2-amino-4-methyl-5-nitropyridine and alpha-cyano-4
      hydroxycinnamic acid/N,N-dimethylaniline (CHCA/DANI)). The properties of these
      direct tissue analysis matrixes, especially CHCA/aniline when compared to CHCA,
      2,5-dihydroxybenzoic acid, and sinapinic acid, are as follows: (1) better
      spectral quality in terms of resolution, sensitivity, intensity, noise, number of
      compounds detected, and contaminant tolerance, (2) better crystallization on
      tissues, i.e., coverage capacity, homogeneity of crystallization, homogeneity of
      crystal sizes, and time of crystallization, (3) better analysis duration in term
      of vacuum stability, (4) better resistance to laser irradiation especially for
      high-frequency lasers, (5) better ionic yield in negative mode, and (6) enough
      fragmentation yield to use the PSD mode on sections to get structural
      information. Applied to MALDI imaging on a MALDI LIFT-TOF with a 50-Hz laser
      frequency, these ionic matrixes have allowed the realization of a new type of
      image in both polarities and reflector mode using the same tissue section. These
      results give a new outlook on peptide tissue profiling by MS, characterization of
      compounds from tissue slices, and MALDI-MS high-quality imaging.

PMID- 16448054
TI  - Multilayer-assembled microchip for enzyme immobilization as reactor toward low
      level protein identification.
AB  - A microchip reactor has been developed on the basis of a layer-by-layer approach
      for fast and sensitive digestion of proteins. The resulting peptide analysis has
      been carried out by matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF MS). Natural polysaccharides, positively charged
      chitosan (CS), and negatively charged hyaluronic acid (HA) were multilayer
      assembled onto the surface of a poly(ethylene terephthalate) (PET) microfluidic
      chip to form a microstructured and biocompatible network for enzyme
      immobilization. The construction of CS/HA assembled multilayers on the PET
      substrate was characterized by AFM imaging, ATR-IR, and contact angle
      measurements. The controlled adsorption of trypsin in the multilayer membrane was
      monitored using a quartz crystal microbalance and an enzymatic activity assay.
      The maximum proteolytic velocity of the adsorbed trypsin was approximately 600
      mM/min mug, thousands of times faster than that in solution. BSA, myoglobin, and
      cytochrome c were used as model substrates for the tryptic digestion. The
      standard proteins were identified at a low femtomole per analysis at a
      concentration of 0.5 ng/muL with the digestion time <5s. This simple technique
      may offer a potential solution for low-level protein analysis.

PMID- 16448056
TI  - Individual acidic organelle pH measurements by capillary electrophoresis.
AB  - This report describes the pH measurement of individual acidic organelles isolated
      from the human leukemia CCRF-CEM and CEM/C2 cells. These cells were allowed to
      endocytose fluorescein tetramethylrhodamine dextran (FRD), a ratiometric probe
      that has fluorescein as a pH-dependent fluorophore and tetramethylrhodamine as a
      pH-independent fluorophore. Isolated organelle fractions from these cells were
      then subjected to capillary electrophoresis with laser-induced fluorescence
      detection (CE-LIF) analysis. The detection of individual organelle fluorescence
      at two different wavelengths, selected on the basis of the emission range of the
      FRD probe, gives a fluorescence intensity ratio used to calculate the pH from a
      calibration curve. This curve was constructed from CE-LIF measurements of
      individual liposomes loaded with several pH buffer standards. The respective
      median pH values are 5.1 +/- 0.2 in CEM/C2 cells and 6.1 +/- 0.4 in CCRF-CEM
      cells. These measurements compare well with pixel-based epifluorescence
      microscopy measurements of whole cells where the corresponding average pH values
      are 5.0 +/- 0.6 (n = 15) and 6.2 +/- 0.7 (n = 15). A pH comparison between the
      two cell types suggests that the lower pH in the CEM/C2 cells may be relevant to
      the protonation and sequestration of weak base anticancer drugs such as
      doxorubicin. The determination of the pH of individual vesicles, liposomes, and
      acidic organelles is a new resource for measuring and investigating the role of
      the acid-base properties of subcellular-size compartments.

PMID- 16448057
TI  - Automated acoustic matrix deposition for MALDI sample preparation.
AB  - Novel high-throughput sample preparation strategies for MALDI imaging mass
      spectrometry (IMS) and profiling are presented. An acoustic reagent multispotter
      was developed to provide improved reproducibility for depositing matrix onto a
      sample surface, for example, such as a tissue section. The unique design of the
      acoustic droplet ejector and its optimization for depositing matrix solution are
      discussed. Since it does not contain a capillary or nozzle for fluid ejection,
      issues with clogging of these orifices are avoided. Automated matrix deposition
      provides better control of conditions affecting protein extraction and matrix
      crystallization with the ability to deposit matrix accurately onto small surface
      features. For tissue sections, matrix spots of 180-200 microm in diameter were
      obtained and a procedure is described for generating coordinate files readable by
      a mass spectrometer to permit automated profile acquisition. Mass spectral
      quality and reproducibility was found to be better than that obtained with manual
      pipet spotting. The instrument can also deposit matrix spots in a dense array
      pattern so that, after analysis in a mass spectrometer, two-dimensional ion
      images may be constructed. Example ion images from a mouse brain are presented.

PMID- 16448058
TI  - Biosensor based on self-assembling acetylcholinesterase on carbon nanotubes for
      flow injection/amperometric detection of organophosphate pesticides and nerve
      agents.
AB  - A highly sensitive flow injection amperometric biosensor for organophosphate
      pesticides and nerve agents based on self-assembled acetylcholinesterase (AChE)
      on a carbon nanotube (CNT)-modified glassy carbon (GC) electrode is described.
      AChE is immobilized on the negatively charged CNT surface by alternatively
      assembling a cationic poly(diallyldimethylammonium chloride) (PDDA) layer and an
      AChE layer. Transmission electron microscopy images confirm the formation of
      layer-by-layer nanostructures on carboxyl-functionalized CNTs. Fourier transform
      infrared reflectance spectrum indicates the AChE was immobilized successfully on
      the CNT/PDDA surface. The unique sandwich-like structure (PDDA/AChE/PDDA) on the
      CNT surface formed by self-assembling provides a favorable microenvironment to
      keep the bioactivity of AChE. The electrocatalytic activity of CNT leads to a
      greatly improved electrochemical detection of the enzymatically generated
      thiocholine product, including a low oxidation overvoltage (+150 mV), higher
      sensitivity, and stability. The developed PDDA/AChE/PDDA/CNT/GC biosensor
      integrated into a flow injection system was used to monitor organophosphate
      pesticides and nerve agents, such as paraoxon. The sensor performance, including
      inhibition time and regeneration conditions, was optimized with respect to
      operating conditions. Under the optimal conditions, the biosensor was used to
      measure as low as 0.4 pM paraoxon with a 6-min inhibition time. The biosensor had
      excellent operational lifetime stability with no decrease in the activity of
      enzymes for more than 20 repeated measurements over a 1-week period. The
      developed biosensor system is an ideal tool for online monitoring of
      organophosphate pesticides and nerve agents.

PMID- 16448059
TI  - Charge reduced electrospray size spectrometry of mega- and gigadalton complexes:
      whole viruses and virus fragments.
AB  - The ability to analyze and identify large macromolecular complexes whose
      molecular weight is beyond the analyzable range of mass spectrometry is of great
      interest. The size of such complexes makes them suitable for analysis via
      mobility size spectrometry. In this work, charge reduced electrospray size
      spectrometry was used for the analysis of bacteriophage viruses with total
      molecular masses ranging from 3.6 MDa up to the gigadalton range. The
      electrospray source used was operated in "cone jet" mode with a mean droplet
      diameter of 170.56 nm. Bacteriophage MS2 was found to have a mobility diameter of
      24.13 +/- 0.06 nm and remain highly viable after the electrospray process. Larger
      bacteriophages T2 and T4 have lengths greater than the diameter of the
      electrospray jet and droplets; thus, they could not be completely enclosed and
      were found to fragment at the virus capsid head-tail noncovalent interface during
      either the jet formation or jet breakup process. No viable T2 or T4 virions were
      detectable after being electrosprayed. While the exact mechanism of fragmentation
      could not be determined, it is proposed here that macromolecular fragmentation at
      noncovalent interfaces occurs due to mechanically and electrically induced
      stresses during jet formation and jet breakup. Bacteriophage T4 capsid heads were
      found to be statistically significantly larger than bacteriophage T2 capsid
      heads, with a mean peak diameter of 88.32 +/- 1.02 nm for T4 and 87.03 +/- 0.18
      nm for T2. While capsid head fragments were detectable, tail and tail-fiber
      fragments could not be detected by size spectrometric analysis. This is
      attributed to the fact that the contractile tails of bacteriophage T2 and T4
      virions mechanically deform to a varying degree while confined within the smaller
      jet and droplets. Further evidence of contractile tail deformation during the
      electrospray process was found by measuring the size spectrum of bacteriophage
      lambda, which has a noncontractile tail. Bacteriophage lambda had two distinct
      peaks in its size spectrum, one corresponding to the capsid head and the other
      corresponding to the tail fragment. Size spectrometry was also used for rapid
      quantification of virus concentrations, thus demonstrating its full capabilities
      in the analysis of large macromolecular complexes.

PMID- 16448060
TI  - Prevention of nonspecific bacterial cell adhesion in immunoassays by use of
      cranberry juice.
AB  - The ability of Vaccinum macrocarpon, the North American cranberry, to prevent
      bacterial adhesion has been used to advantage in the prevention of urinary tract
      infections and has recently been described for the prevention of adhesion of
      bacteria responsible for oral infections and stomach ulcers. This report
      documents the ability of cranberry juice to reduce nonspecific adhesion of
      bacteria to the borosilicate glass microscope slides used in an immunoarray
      biosensor format. Nonspecific binding of analytes in the array sensor leads to
      high background signals that cause increased detection limits and false
      positives. Reduction in background-to-signal ratios can be seen as the juice
      concentration is increased from 0 to 50% of the sample. This impact cannot be
      duplicated with grape, orange, apple, or white cranberry juice. Sugar content and
      pH have been eliminated as the agents in the juice responsible for the anti
      adhesive activity.

PMID- 16448061
TI  - Pseudolinear gradient ultrahigh-pressure liquid chromatography using an injection
      valve assembly.
AB  - The use of ultrahigh pressures in liquid chromatography (UHPLC) imposes stringent
      requirements on hardware such as pumps, valves, injectors, connecting tubing, and
      columns. One of the most difficult components of the UHPLC system to develop has
      been the sample injector. Static-split injection, which can be performed at
      pressures up to 6900 bar (100,000 psi), consumes a large sample volume and is
      very irreproducible. A pressure-balanced injection valve provided better
      reproducibility, shorter injection time, reduced sample consumption, and greater
      ease of use; however, it could only withstand pressures up to approximately 1000
      bar (15,000 psi). In this study, a new injection valve assembly that can operate
      at pressures as high as 2070 bar (30,000 psi) was evaluated for UHPLC. This
      assembly contains six miniature electronically controlled needle valves to
      provide accurate and precise volumes for introduction into the capillary LC
      column. It was found that sample volumes as small as several tenths of a
      nanoliter can be injected, which are comparable to the results obtained from the
      static-split injector. The reproducibilities of retention time, efficiency, and
      peak area were investigated, and the results showed that the relative standard
      deviations of these parameters were small enough for quantitative analyses.
      Separation experiments using the UHPLC system with this new injection valve
      assembly showed that this new injector is suitable for both isocratic and
      gradient operation modes. A newly designed capillary connector was used at a
      pressure as high as 2070 bar (30,000 psi).

PMID- 16448062
TI  - Atomization of hydride with a low-temperature, atmospheric pressure dielectric
      barrier discharge and its application to arsenic speciation with atomic
      absorption spectrometry.
AB  - This paper describes a novel hydride atomizer based on atmospheric pressure
      dielectric barrier discharge (DBD) plasma. The plasma was generated with a 3700
      V, 20.3-kHz, and 5-W electrical power supply and easily sustained with inert
      gases (He or Ar) at a flow rate of 250 mL.min(-1) after optimization. However, it
      cannot be sustained with N2. This atomizer offers the advantages of low operation
      temperature and low power consumption in comparison with the currently used
      electrothermal quartz atomization operated at 900 degrees C with a power supply
      of several hundred watts. To confirm the utility of the proposed atomizer, four
      arsenic species (As(III), As(V), monomethylarsonic acid (MMA), dimethylarsinic
      acid (DMA)) were determined by the present atomization technique. A hyphenation
      of HPLC coupled to hydride generation AAS with the optimized DBD atomizer has
      been successfully used for the speciation of arsenic in order to demonstrate the
      potential of this atomizer in the present study. The characteristics of the DBD
      atomizer and the effects of different parameters (discharge gas, gas flow rate,
      voltage, HCl concentration, KBH4 concentration) are discussed in the paper.
      Compared with other hydride atomization techniques, the proposed method shows the
      following features: (1) small size (70 mm x 15 mm x 5 mm), which is preferable
      for the miniaturization of the total analytical system; (2) low power consumption
      (< or =5 W), which indicates the possibility of the development of portable,
      fieldable analytical instrumentation for in situ detection using battery as power
      supply; (3) low atomizer temperature (approximately 70 degrees C), which is in
      favor of the compactness of the total instruments; (4) avoidance of residue
      moisture removal in comparison with the existed GD system, which leads to the
      facility of the system. The analytical figures of the present technique were
      evaluated. The detection limits of As(III), As(V), MMA, and DMA obtained with HG
      DBD-AAS were 1.0, 11.8, 2.0, and 18.0 microg.L(-1), respectively. The accuracy of
      the system was verified by the determination of arsenic in reference material of
      orchard leaves SRM 1571. The concentration of As determined by the present method
      agreed well with the reference values. The speciation of arsenic in the freeze
      dried urine SRM 2670 were carried out, and the results obtained were in agreement
      with the results of HPLC-ICPMS and the reported values by other laboratories.

PMID- 16448063
TI  - A stepwise stoichiometric representation to confirm the dependence of
      pesticide/humic acid interactions on salt concentration and to test the
      performance of a silica bonded humic acid column.
AB  - In a previous paper (Andre et al., in press), a novel chromatographic column was
      developed in our laboratory for studying the binding of pesticides with humic
      acid (HA), the main organic component in soil. It was demonstrated that this
      column supported a low fraction of organic modifier in the aqueous mobile phase
      (<0.25 (v/v)). To overcome this limitation for a practical use, a column in which
      the stationary phase was based on silica gel with chemically bonded humic acid
      was created. It was shown that this novel HA column supported a higher methanol
      fraction (<0.55 (v/v)). As well, the dependence of pesticide/humic acid
      interactions on salt (sodium chloride) concentration has been expressed in terms
      of a stepwise stoichiometric representation, which leads to a specific equation
      for the partition of the added salt between the pesticide molecule, the HA, and
      the pesticide/HA complex. Based on this novel equation, the dependence of the
      pesticide/humic acid association on the salt concentration can be formulated via
      a relation similar to the one of Tanford. In addition, for the first time, the
      calculation of the affinity energy distribution for different values of the salt
      concentration in the mobile phase confirmed the existence of several types of
      binding sites on the HA macromolecule.

PMID- 16448064
TI  - Evaluation of leaf-derived extracts as an environmentally sustainable source of
      essential oils by using gas chromatography-mass spectrometry and enantioselective
      gas chromatography-olfactometry.
AB  - In consideration of the world's present environmental situation and the threat of
      species extinction, investigations concerning alternative sustainable sources of
      natural substances represent an extremely important issue. In this respect, the
      present research is focused on the analytical evaluation of Brazilian rosewood
      (Aniba rosaeodora Ducke) leaves, as an alternative source (with respect to wood)
      of rosewood essential oil and, as such, of natural linalool, which is extensively
      used in perfumery. Enantioselective-gas chromatography-olfactometry (Es-GC-O) was
      used as a tool for the simultaneous stereodifferentiation and olfactive
      evaluation of the volatile optically active components present in the analyzed
      samples. In addition to Es-GC-O analyses, direct olfactive analyses were also
      performed, enabling the evaluation of the global aroma exerted by each sample and
      the influence of each linalool antipode, as also other minor compounds. The
      samples were also submitted to gas chromatography-mass spectrometric analysis,
      thus establishing their chemical profiles. The assessment of enantiopure chiral
      compounds through Es-GC-O, along with direct olfactive analyses, confirmed that
      the leaves are a potential substituent for wood in the extraction of Brazilian
      rosewood essential oil, representing a sustainable nonwood source of natural
      linalool.

PMID- 16448065
TI  - Multistage mass spectrometric sequencing of keratan sulfate-related
      oligosaccharides.
AB  - To establish a universal protocol for sequencing keratan sulfate (KS) using mass
      spectrometry (MS), systematic electrospray ionization-MSn fragmentation
      experiments were carried out for 10 KS-related oligosaccharides of defined
      structure. Under the experimental conditions employed, fully charged molecular
      related ions were observed as dominant peaks in all MS(1) spectra, which clearly
      reflected the number of sulfates and sialic acids in the oligosaccharide
      structures. In the subsequent MS2, almost all of the oligosaccharides gave
      fragment ions corresponding to their dehydrated molecular-related ions as well as
      (0,2)A(r) scission ions (according to the nomenclature developed by Domon and
      Costello, where "r" represents the reducing end in this study). Further
      fragmentation of the (0,2)A(r) ions in MS3 predominantly yielded the
      corresponding (2,4)A(r) ions. Finally, in MS(4), these (2,4)A(r) ions were
      subjected to extensive glycosidic cleavage. Hence, the MS4 data of KS
      oligosaccharides provided sufficient information for their sequence
      determination. In addition, some important features of MSn fragmentation became
      evident. These findings should lead to the establishment of consensus rules
      applied for KS oligosaccharides, including those previously unidentified, and
      also accelerate functional studies on KS, i.e., KS-related glycosaminoglycomics.

PMID- 16448066
TI  - High-throughput screening for the asymmetric transformation reaction of L
      histidine to D-histidine by capillary array electrophoresis.
AB  - Asymmetric transformation reaction of L-histidine to D-histidine was studied by
      homemade capillary array electrophoresis for the first time. The enantiomeric
      excess value of asymmetric histidine products can be directly determined from the
      electrophoretogram of capillary array electrophoresis. The experiment results
      showed that the optimized asymmetric transformation reaction condition was in the
      presence of salicylaldehyde as catalyst and acetic acid as solvent.

PMID- 16448067
TI  - Real-time image acquisition for absorbance detection and quantification in thin
      layer chromatography.
AB  - This paper presents the first quantitative study of real-time acquisition of
      images of spots on thin-layer chromatographic plates during development.
      Procedures are described for imaging using a CCD camera and for image processing,
      incorporating corrections for fixed pattern effects and compensation for the
      moving solvent front, to measure the absorbance of the analyte. Imaging of Sudan
      II was carried out in transmission mode, and peak areas were found to be time
      independent. Quantification of the relationship between peak area and sample
      loading was established over the range 1-50 ng. After averaging 55 images
      obtained during a single chromatographic run, which attenuates noise
      contributions from local nonuniformities in the sorbent layer, precision and
      detection limits were found to be comparable with values obtained in previous
      work using offline measurements.

PMID- 16448068
TI  - High-throughput axial MALDI-TOF MS using a 2-kHz repetition rate laser.
AB  - A high-throughput axial MALDI-TOF mass spectrometer utilizing a laser with a 2
      kHz pulse repetition-rate was constructed and tested. This fast mass spectrometer
      provided a data acquisition rate 10 times faster than a commercially available
      (200 Hz) axial mass spectrometer, while maintaining comparable limits of
      detection (200 amol of Glu fib peptide). Mass resolution, only slightly less than
      the commercial instrument (10 000 vs 14 000), was sufficient for baseline
      resolution of isotopic clusters of peptides with m/z <2700. A new method of mass
      calibration, which combined a limited number of internal and external standards,
      provided the same 15 ppm mass accuracy over the entire sample plate on either
      instrument. Implementing the 2-kHz laser required a faster data acquisition
      system and high-voltage pulse electronics, together with a novel strategy for
      rapid sample plate movements during acquisition, to achieve a sample analysis
      rate of up to 2 spots/s (with 800 shots/spot). The overall performance of the
      fast MALDI-TOF MS instrument was demonstrated by the acquisition, in 12 min, of
      an LC-MS data set from a plate of 625 fractions collected during LC separation of
      an 16O/18O differentially labeled proteomic sample of a tryptic digest of an E.
      coli lysate.

PMID- 16448069
TI  - Selective determination of native fluorescent bioamines through precolumn
      derivatization and liquid chromatography using intramolecular fluorescence
      resonance energy transfer detection.
AB  - In this paper, we introduce a novel approach for the highly selective and
      sensitive analysis of native fluorescent bioamines (indoleamines and
      catecholamines). This method is based on intramolecular fluorescence resonance
      energy transfer (FRET) detection in a liquid chromatography (LC) system following
      precolumn derivatization of the bioamines' amino groups. In this detection
      process, we monitored the FRET from the native fluorescent moieties (donor) to
      the derivatized fluorophore (acceptor). From a screening study involving 15
      fluorescent reagents, we found that o-phthalaldehyde (OPA) generated the FRET
      most effectively. The OPA derivatives of the native fluorescent bioamines emitted
      OPA fluorescence (445 nm) through an intermolecular FRET process when they were
      excited at the excitation maximum wavelengths of the native fluorescent bioamines
      (280 nm). The generation of FRET was confirmed through comparison with the
      analysis of a nonfluorescent amine (isoleucine) performed using LC and a three
      dimensional fluorescence detection system. We were able to separate the OPA
      derivatives of the indoleamines and catecholamines when performing LC on an ODS
      column. The detection limits (signal-to-noise ratio, 3) for the indoleamines and
      catecholamines, at a 20-muL injection volume, were 17-120 and 28-200 fmol,
      respectively. The sensitivity of the intramolecular FRET-forming derivatization
      method is higher than those of systems that take advantage of both native
      fluorescence detection (i.e., without derivatization) and the conventional
      detection of OPA derivatives. Furthermore, this method provides enough
      selectivity and sensitivity for the determination of the indoleamines present in
      the urine of healthy humans.

PMID- 16448070
TI  - Engineered superoxide dismutase monomers for superoxide biosensor applications.
AB  - Because of its high reaction rate and specificity, the enzyme superoxide
      dismutase (SOD) offers great potential for the sensitive quantification of
      superoxide radicals in electrochemical biosensors. In this work, monomeric
      mutants of human Cu,Zn-SOD were engineered to contain one or two additional
      cysteine residues, which could be used to bind the protein to gold surfaces, thus
      making the use of promotor molecules unnecessary. Six mutants were successfully
      designed, expressed, and purified. All mutants bound directly to unmodified gold
      surfaces via the sulfur of the cysteine residues and showed a quasi-reversible,
      direct electron transfer to the electrode. Thermodynamic and kinetic parameters
      of the electron transfer were characterized and showed only slight variations
      between the individual mutants. For one of the mutants, the interaction with the
      superoxide radical was studied in more detail. For both partial reactions of the
      dismutation, an interaction between protein and radical could be shown. In an
      amperometric biosensorial approach, the SOD-mutant electrode was successfully
      applied for the detection of superoxide radicals. In the oxidation region, the
      electrode surpassed the sensitivity of the commonly used cytochrome c electrodes
      by approximately 1 order of magnitude while not being limited by interferences,
      but the electrode did not fully reach the sensitivity of dimeric Cu,Zn-SOD
      immobilized on MPA-modified gold.

PMID- 16448071
TI  - Analytical performance of polymer-based microfluidic devices fabricated by
      computer numerical controlled machining.
AB  - A study comparing the electrophoretic separation performance attainable from
      microchips molded by masters fabricated using conventional CNC machining
      techniques with commercial microchips, wire imprinted microchips, and microchips
      from LIGA molding devices is presented. An electrophoresis-based detection system
      using fluorescence microscopy was used to determine the analytical utility of
      these microchips. The separation performance of CNC microchips was comparable to
      commercially available microchips as well as those fabricated from LIGA masters.
      The important feature of the CNC machined masters is that they have rapid design
      to-device times using routinely available machining tools. This low-cost
      prototyping approach provides a new entry point for researchers interested in
      thermoplastic microchips and can accelerate the development of polymer-based lab
      on-a-chip devices.

PMID- 16448072
TI  - How to assess the limits of ion-selective electrodes: method for the
      determination of the ultimate span, response range, and selectivity coefficients
      of neutral carrier-based cation selective electrodes.
AB  - The span and range of an ion-selective electrode (ISE) has been identified by
      IUPAC as a potential or activity difference between the upper and lower detection
      limits of the electrode. Once the span is known, the ultimately attainable
      detection limit of the ISE can be calculated using its theoretical response
      slope. In this paper, we propose an original method for the determination of the
      ultimate span and response range of ISEs. The simple measurement of span is
      recommended to aid the fast screening of novel ionophores and help to focus
      optimization processes to the most promising candidates. The measurement of span
      is combined with a generally applicable procedure for the determination of the
      three seminal parameters of ISEs: the response slope, the ultimate selectivity
      coefficients, and detection limit. In the proposed procedure, following the span
      measurement, two subsequent exponential dilution experiments are completed in
      which the responses of the electrode for the primary and the interfering ions are
      tested using a solution of a discriminated ion and deionized water as diluting
      electrolytes in consecution. The advantages and the practical usefulness of the
      proposed methods and procedures are demonstrated through the evaluation of the
      performance characteristics of novel and well-characterized ionophore-based
      potassium and calcium sensors.

PMID- 16448073
TI  - Development of a nanowire-based test bed device for molecular electronics
      applications.
AB  - In this paper, we present a novel test bed system which we believe addresses
      several key challenges in molecular electronics, i.e., the need to fabricate
      metal-molecule-metal junctions that have the potential to facilitate single
      molecule measurements, are easily characterized, and are reproducible. The system
      is based upon template-electrodeposited metal nanowires incorporating a self
      assembled monolayer spacer that are fabricated into electrical devices using
      direct-write photolithography. Removal of the spacer leaves a nanometer-sized,
      characterizable gap to which nanoparticles or a test molecule of interest can be
      attached postfabrication. Here we report the fabrication procedure together with
      results showing the application of these devices to the study of the i/V
      characteristics of Au nanoparticles at cryogenic temperatures. These data
      demonstrate that the performance of these easily produced, inexpensive, novel
      devices compares favorably to that of devices made using preexisting methods.

PMID- 16448075
TI  - DNA covalent immobilization onto screen-printed electrode networks for direct
      label-free hybridization detection of p53 sequences.
AB  - A new electrochemical biochip for the detection of DNA sequences was developed.
      The entire biochip-i.e., working, reference, and counter electrodes-was
      constructed based on the screen-printing technique and exhibits eight working
      electrodes that could be individually addressed and grafted through a simple
      electrochemical procedure. Screen-printed electrode networks were functionalized
      electrochemically with 1-ethyl-3-(3dimethylaminopropyl)carbodidiimide according
      to a simple procedure. Single-stranded DNA with a C6-NH(2) linker at the 5'-end
      was then covalently bound to the surface to act as probe for the direct,
      nonlabeled, detection of complementary strands in a conductive liquid medium. In
      the present system, the study was focused on a particular codon (273) localized
      in the exon 8 of the p53 gene (20 mer, TTGAGGTGCATGTTTGTGCC). The integrity of
      the immobilized probes and its ability to capture target sequences was monitored
      through chemiluminescent detection following the hybridization of a peroxidase
      labeled target. The grafting of the probe at the electrode surface was shown to
      generate significant shifts of the Nyquist curves measured in the 10-kHz to 80-Hz
      range. These variations of the faradaic impedance were found to be related to
      changes of the double layer capacitance of the electrochemical system's
      equivalent circuit. Similarly, hybridization of complementary strands was
      monitored through the measurements of these shifts, which enabled the detection
      of target sequences from 1 to 200 nM. Discrimination between complementary,
      noncomplementary, and single-nucleotide mismatch targets was easily accomplished.

PMID- 16448074
TI  - Parallel picoliter rt-PCR assays using microfluidics.
AB  - The development of microfluidic tools for high-throughput nucleic acid analysis
      has become a burgeoning area of research in the post-genome era. Here, we have
      developed a microfluidic chip to perform 72 parallel 450-pL RT-PCRs. We took
      advantage of Taqman hydrolysis probe chemistry to detect RNA templates as low as
      34 copies. The device and method presented here may enable highly parallel single
      cell gene expression analysis.

PMID- 16448076
TI  - Development of a nebulizer for a sheathless interfacing of NanoHPLC and ICPMS.
AB  - A novel nebulizer (nDS-200) working at sample uptake rates of less than 500 nL
      min(-1) was developed for a sheathless interfacing of nanoHPLC (75-microm column
      i.d.) with ICPMS. It was based on a hollow fused-silica needle of which the tip
      (i.d. 10 microm, o.d. 20 microm) centered in a 254-microm-i.d. sapphire orifice.
      The nebulizer, equipped with a 3-cm(3) drain-free vaporization chamber, enabled a
      stable introduction into an ICP of aqueous mobile phases containing up to 95%
      acetonitrile at eluent flow rates between 50 and 450 nL min(-1). The low dead
      volume of the interface resulted in a peak width of 1.3 s (at half-height) and
      the entirely preserved chromatographic resolution. An example application of the
      coupling to the analysis of a tryptic digest of a SIP18 protein containing two to
      nine selenomethionine residues was described. The absolute detection limit was 25
      fg (80Se), which allowed the detection of low-abundant selenopeptides at the
      femtomole level. In contrast to electrospray MS, the ICPMS detection in nanoHPLC
      is unaffected by the coeluting matrix and concomitant compounds and offers an
      elegant method for the detection and quantification of minor heteroelement
      containing species prior to or in parallel with ESI MS analysis.

PMID- 16448080
TI  - Directed DNA metallization.
AB  - Genes of interest can be selectively metallized via the incorporation of modified
      triphosphates. These triphosphates bear functions that can be further derivatized
      with aldehyde groups via the use of click chemistry. Treatment of the aldehyde
      labeled gene mixture with the Tollens reagent, followed by a development process,
      results in the selective metallization of the gene of interest in the presence of
      natural DNA strands.

PMID- 16448081
TI  - Analysis of lanthanide-induced NMR shifts of the Ce@C82 anion.
AB  - The mapping of bond connectivity in the carbon cage of [Ce@C82]- and full
      assignment of the NMR lines were successfully achieved by means of 2D INADEQUATE
      NMR measurement. Paramagnetic NMR analysis shows that the Ce atom in [Ce@C82]- is
      located at an off-centered position adjacent to a hexagonal ring along the C2
      axis of the C2v-C82 cage.

PMID- 16448082
TI  - Synthesis and structural characterization of endohedral
      pyrrolidinodimetallofullerene: La2@C80(CH2)2NTrt.
AB  - The endohedral pyrrolidinodimetallofullerene, La2@C80(CH2)2NTrt (Trt =
      triphenylmethyl), was successfully synthesized and characterized. X-ray
      crystallographic and NMR spectroscopic analyses reveal that two La atoms in the
      6,6-adduct are localized at the stable site on the mirror plane. Theoretical
      calculation also suggests the localization of two La atoms in the 6,6-adduct.

PMID- 16448084
TI  - Palladium(0)-catalyzed alkylative cyclization of alkynals and alkynones:
      remarkable trans-addition of organoboronic reagents.
AB  - Palladium/monophosphine complexes catalyze trans-selective arylative,
      alkenylative, and alkylative cyclization reactions of alkynals and alkynones with
      organoboronic reagents. These reactions afford six-membered allylic alcohols with
      endo-tri- or tetrasubstituted olefin groups and/or five-membered counterparts
      with exo olefin groups. The ratios of these products are dramatically affected by
      alkyne substituents as well as the phosphine ligand. The remarkable trans
      selectivity of the process results from the novel reaction mechanism involving
      oxidative addition without oxametallacycle formation.

PMID- 16448083
TI  - PNA-based reagents for the direct and site-specific synthesis of thymine dimer
      lesions in genomic DNA.
AB  - An acetophenone containing PNA-based reagent was designed for the direct and site
      specific synthesis of a cis-syn thymidine dimer lesion in genomic DNA.

PMID- 16448085
TI  - Free energies of molecular crystal surfaces by computer simulation: application
      to tetrathiophene.
AB  - We describe a general simulation protocol for the evaluation of the surface free
      energies of molecular crystals, which are of broad interest for phenomena such as
      polymorphism and crystal growth. The method has been applied to selected surfaces
      of two polymorphs of tetrathiophene. The simulations highlight an important
      temperature-dependent entropic contribution to the surface free energies, which
      is not included in widely used static simulations of surface structure and
      energetics.

PMID- 16448086
TI  - Non-SELEX selection of aptamers.
AB  - Aptamers are typically selected from libraries of random DNA (or RNA) sequences
      by SELEX, which involves multiple rounds of alternating steps of partitioning and
      PCR amplification. Here we report, for the first time, non-SELEX selection of
      aptamers-a process that involves repetitive steps of partitioning with no
      amplification between them. A highly efficient affinity method, non-equilibrium
      capillary electrophoresis of equilibrium mixtures (NECEEM), was used for
      partitioning. We found that three steps of NECEEM-based partitioning in the non
      SELEX approach were sufficient to improve the affinity of a DNA library to a
      target protein by more than 4 orders of magnitude. The resulting affinity was
      higher than that of the enriched library obtained in three rounds of NECEEM-based
      SELEX. Remarkably, NECEEM-based non-SELEX selection took only 1 h in contrast to
      several days or several weeks required for a typical SELEX procedure by
      conventional partitioning methods. In addition, NECEEM-based non-SELEX allowed us
      to accurately measure the abundance of aptamers in the library. Not only does
      this work introduce an extremely fast and economical method for aptamer
      selection, but it also suggests that aptamers may be much more abundant than they
      are thought to be. Finally, this work opens the opportunity for selection of drug
      candidates from libraries of small molecules, which cannot be PCR-amplified and
      thus are not approachable by SELEX.

PMID- 16448087
TI  - Multifunctional chemical vapor sensors of aligned carbon nanotube and polymer
      composites.
AB  - Partially coating perpendicularly aligned carbon nanotube arrays with an
      appropriate polymer thin film along their tube length provides a novel concept
      for developing new sensors of high sensitivity, good selectivity, and excellent
      environmental stability for the detection of a broad class of chemical vapors
      with low power consumption. The absorption and desorption of chemical vapors by
      the polymer matrix cause changes in the inter-tube distance and, hence, the
      surface resistance across the nanotube film. Simple measurements of the
      resistance change, therefore, constitute the nanotube-polymer chemical vapor
      sensors. These rationally designed, aligned carbon nanotube-polymer composite
      films are flexible and can be effectively integrated into many systems for a wide
      range of potential applications, including their use as multifunctional sensors
      for sensing chemical vapors, mechanical deformations, thermal and optical
      exposures.

PMID- 16448088
TI  - Self-adhesion among phospholipid vesicles.
AB  - A compound was synthesized that binds to a phospholipid bilayer via a hydrophobic
      steroid thereby projecting a strong multi-hydrogen bonding unit into the
      surrounding water. As shown by light scattering, light microscopy, and cryo
      HRSEM, this latter unit self-adheres and induces membrane-membrane attachments,
      as found in many biological systems.

PMID- 16448090
TI  - One-dimensional metallic conducting pathway of cyclohexyl-substituted spiro
      biphenalenyl neutral radical molecular crystal.
AB  - The unprecedented metallic character of the cyclohexyl-substituted spiro
      biphenalenyl neutral radical molecular crystal (5) suggested by its Pauli
      paramagnetism [Science 2005, 309, 281] is contradicted by the thermally activated
      conduction measured along the needle axis of crystal 5 and by an optical gap of
      Eg = 0.34 eV. Herein we provide the first high quality ab initio electronic
      structure calculations using density functional theory to reconcile these
      properties. The calculations point toward 5 being a quasi one-dimensional (1-D)
      material, with a 1-D conducting pathway along the [101] pi-chain direction. Along
      any directions other than the pi-chain, conduction is impeded by the small
      interchain overlap. 5 has a quarter-filled band structure with a density of
      states of N(Ef) = 7.5 states eV-1 at the Fermi level, leading to a metallic
      character along the pi-chain.

PMID- 16448089
TI  - Further study of the reaction of Fe2+ with CN-: synthesis and characterization of
      cis and trans [FeII,III(CN)4L2]n- complexes.
AB  - The reaction of Fe2+ with CN-, which was first performed in 1704, has been used
      to synthesize a new series of basic [FeII,III(CN)4L2]n- complexes, where L is a
      monodentate ligand. trans-Na2[FeII(CN)4(DMSO)2] and cis
      [NEt4]2[FeII(CN)4(pyridine)2] are synthesized by the direct reaction of FeCl2
      with 4 equiv of CN- in DMSO or pyridine. Air oxidation of the latter compound
      gives cis-[NEt4][FeIII(CN)4(pyridine)2]. The non-cyanide ligands in these
      complexes undergo facile ligand exchange reactions with solvent. Reaction of cis
      [NEt4]2[FeII(CN)4(pyridine)2] with CO at room temperature gives trans
      [NEt4]2[FeII(CN)4(pyridine)(CO)].

PMID- 16448091
TI  - The dehydratase activity of lacticin 481 synthetase is highly processive.
AB  - Lacticin 481 synthetase (LctM) is a bifunctional enzyme that undertakes
      dehydration and cyclization in the structural region of the pre-lacticin peptide
      (LctA) to introduce three thioether rings and one dehydrobutyrine residue. The
      order and timing of these events has been investigated employing high-resolution
      ESI-FTMS-based tandem MS/MS techniques and chemical derivatization. LctM
      demonstrates highly processive behavior as seen by MS analysis of the reaction
      course of dehydration. Furthermore, cyclization is not tightly coupled to
      dehydration and follows at a later stage of the enzymatic reaction.

PMID- 16448092
TI  - Thionitroxides, RSNHO*: the structure of the SNO moiety in "S-Nitrosohemoglobin",
      a possible NO reservoir and transporter.
AB  - Nitric oxide (NO) plays important roles in many biological processes. S
      Nitrosothiols have long been believed to have significant roles in NO
      biochemistry. The modified cysteine residue of hemoglobin was previously
      identified as a distorted S-nitrosothiol (RSNO) or an S-hydroxyamino radical
      (RSN*OH). Here we show that a thionitroxide (RSNHO*, S-aminyloxyl radical) is
      likely the observed species. Computational studies show that the thionitroxide is
      the only structure consistent with the electron density in the hemoglobin
      Cysbeta93-SNO structure previously reported. Although a metastable adduct, the
      thionitroxide in a hydrogen-bonding environment can form readily and release NO
      upon exposure to an aqueous environment. The thionitroxides could be responsible
      for the biological effects attributed to S-nitrosothiols or could serve as
      precursors to S-nitrosothiols in oxidative conditions.

PMID- 16448093
TI  - Highly enantioselective synthesis of tetrahydro-beta-carbolines and tetrahydro
      gamma-carbolines via Pd-catalyzed intramolecular allylic alkylation.
AB  - A novel Pd-catalyzed intramolecular allylic alkylation of indoles allows THBCs
      and THGCs to be effectively synthesized in high yields and excellent enantiomeric
      excesses (ee up to 97%).

PMID- 16448094
TI  - A new approach to promoting sluggish Diels-Alder reactions: dihapto-coordination
      of the diene.
AB  - The cycloaddition between 1,3-cyclohexadiene and various enones and enals (methyl
      vinyl ketone, ethyl vinyl ketone, methacrolien) is accomplished at room
      temperature in yields ranging from 51 to 68% without the use of Lewis acids, high
      pressures, or microwave reactors. This normally sluggish cyclization is
      accomplished by precoordination of the diene to a pi-basic molybdenum complex.
      The eta2-bound metal is thought to promote a Michael reaction between the
      uncoordinated portion of the diene and the enone, and the resulting enolate then
      closes to form the cycloalkene product. The organic cycloadduct is removed by
      oxidation with air or with silver triflate in nearly quantitative yield. For more
      sterically hindered enones (e.g., mesityl oxide) and for methyl acrylate, the
      desired outcome requires the use of BF3.OEt2, and yields are significantly lower
      (15-35%)

PMID- 16448096
TI  - Ion pair driven self-assembly of a flexible bis-zwitterion in polar solution:
      formation of discrete nanometer-sized cyclic dimers.
AB  - The self-complementary flexible bis-zwitterion 1 forms discrete nanometer-sized
      cyclic dimers via ion pair driven self-assembly even in polar solvents. The
      existence of such dimers was confirmed by DOSY NMR, FAB-MS, and scattering
      experiments (DLS, SANS) which all indicate the concentration-dependent formation
      of cyclic dimers with a hydrodynamic radius of rH approximately 2.5 nm in
      solution.

PMID- 16448095
TI  - Priming type II polyketide synthases via a type II nonribosomal peptide
      synthetase mechanism.
AB  - Benzoic acid priming of the enterocin and actinorhodin type II polyketide
      synthase complexes was accomplished in vitro via an unprecedented type II
      nonribosomal peptide synthetase-like mechanism involving the benzoate:acyl
      carrier protein (ACP) ligase EncN and the ACP EncC. The transfer of the aryl acid
      to the ACP is ATP-dependent, yet coenzyme A-independent, as characterized with
      radiolabeled substrates and protein mass spectrometry. Subsequent transport of
      the ACP-bound aryl group to the native enterocin and the aberrant actinorhodin
      ketosynthase chain length factor heterodimers was further demonstrated, thereby
      demonstrating the potential of this biocatalyst for engineering diverse aryl
      primed aromatic polyketide agents.

PMID- 16448097
TI  - A two-stage one-pot enzymatic synthesis of TDP-L-mycarose from thymidine and
      glucose-1-phosphate.
AB  - This report describes a procedure combining six enzymes native to Escherichia
      coli or Salmonella typhi, such as thymidine kinase (TK), thymidylate kinase
      (TMK), nucleoside diphosphate kinase (NDK), pyruvate kinase (PK; for ATP
      regeneration), TDP-glucose synthetase (RfbA), and TDP-glucose 4,6-dehydratase
      (RfbB), with five enzymes from Streptomyces fradiae, such as TylX3, TylC1, TylC3,
      TylK, and TylC2, that resulted in the biosynthesis of TDP-l-mycarose from glucose
      1-phosphate and thymidine. This two-stage one-pot approach can be readily applied
      to the synthesis of other unusual sugars.

PMID- 16448098
TI  - Low-valent niobium-mediated double activation of C-F/C-H bonds: fluorene
      synthesis from o-arylated alpha,alpha,alpha-trifluorotoluene derivatives.
AB  - By the treatment of 0.3 molar amount of NbCl5 and LiAlH4, o-arylated
      alpha,alpha,alpha-trifluorotoluenes afforded fluorene derivatives in good yields.
      C-F bonds of the CF3 group and the neighboring ortho C-H bond were doubly
      activated to give the coupling products.

PMID- 16448099
TI  - Highly porous fibers by electrospinning into a cryogenic liquid.
AB  - Highly porous fibers of various polymers were created by electrospinning with a
      modified collector. A bath of liquid nitrogen was used to freeze the fibers,
      inducing a phase separation between the polymer and the solvent. When the solvent
      was removed in vacuo, highly porous fibers were obtained. Poly(styrene),
      poly(acrylonitrile), poly(vinylidene fluoride), and poly(epsilon-caprolactone)
      were all electrospun into porous fibers using this simple method. These porous
      fibers have a range of potential applications in encapsulation, controlled
      release, superhydrophobic coating, and lightweight reinforcement.

PMID- 16448100
TI  - The role of methyl groups in the formation of hydrogen bond in DMSO-methanol
      mixtures.
AB  - When examining the formation energetics of a hydrogen-bonded complex R-X-H...Y
      R', focus has been almost always on the atoms directly involved, namely the atoms
      X, Y, and H. Little attention has been paid to the effects of the secondary alkyl
      groups R and R'. Taking dimethyl sulfoxide (DMSO)-methanol binary system as an
      example, we have studied the roles of the alkyl groups in stabilizing the
      hydrogen bonds by employing FTIR and NMR techniques and quantum chemical
      calculations. We found that methyl groups play different roles in response to the
      hydrogen-bonding interactions. The methyl groups of DMSO are electron-donating,
      whereas that of methanol is electron-withdrawing, both making positive
      contributions. The findings reveal non-negligible effects of secondary alkyl
      groups in hydrogen bonding interaction and may shed light on the understanding of
      other more complicated hydrogen-bonded systems in chemical and biological
      systems.

PMID- 16448101
TI  - Oximate-bridged trinuclear Dy-Cu-Dy complex behaving as a single-molecule magnet
      and its mechanistic investigation.
AB  - Lanthanide ions are supposed to be promising candidates for the elements of
      single-molecule magnets (SMMs) because of the large magnetic momentum and
      anisotropy. We have established the [Dy2Cu] complex as a new SMM. A plausible
      mechanism for quantum tunneling of magnetization is proposed for the first time
      among the 4f-3d heterometallic SMMs. The magnetic coupling parameter between Dy
      and Cu ions was well-defined as -0.155 K.

PMID- 16448102
TI  - Efficient synthesis of cyclopentenones from enynyl acetates via tandem Au(I)
      catalyzed 3,3-rearrangement and the Nazarov reaction.
AB  - A highly efficient method for the synthesis of versatile cyclopentenones from
      readily available enynyl acetates via tandem Au(I)-catalyzed 3,3-rearrangement
      and the Nazarov reaction is developed. Significant substrate flexibility and
      excellent control of the double bond position in the cyclopentenone ring render
      this an attractive method for cyclopentenone synthesis.

PMID- 16448104
TI  - Anti-markovnikov N-H and O-H additions to electron-deficient olefins catalyzed by
      well-defined Cu(I) anilido, ethoxide, and phenoxide systems.
AB  - The monomeric Cu(I) complexes (IPr)Cu(Z) (IPr = 1,3-bis(2,6
      diisopropylphenyl)imidazol-2-ylidene, Z = NHPh, OEt, or OPh) react with YH (Y =
      PhNH, PhCH2NH, EtO, or PhO) to catalytically add Y-H bonds across the C=C bond of
      electron-deficient olefins to yield anti-Markovnikov organic products. Catalytic
      activity has been observed for olefins CH2C(H)(X) with X = CN, C(O)Me, or CO2Me
      as well as crotononitrile. Preliminary studies implicate an intermediate in which
      the C-Y bond forms through a nucleophilic addition pathway.

PMID- 16448103
TI  - Dynamics of nitric oxide rebinding and escape in horseradish peroxidase.
AB  - Ultrafast kinetic measurements of NO rebinding to horseradish peroxidase (HRP)
      are reported for the first time. The geminate kinetics are found to be
      exponential for all HRP samples studied. The ferric forms of HRP have NO geminate
      recombination time constants in the range of 15-30 ps, while the ferrous form has
      a time constant of approximately 7 ps. The simple exponential NO geminate
      kinetics found for HRP demonstrate that heme relaxation is not the underlying
      source of the nonexponential NO rebinding in myoglobin (Mb). The NO ligand escape
      rates from HRP are also determined, and they are found to depend dramatically on
      the presence or absence of the competitive inhibitor benzohydroxamic acid (BHA).
      The kinetic results indicate that, in contrast to Mb, there is direct solvent
      access to the distal heme pocket of HRP.

PMID- 16448105
TI  - Total synthesis of (+/-)-welwitindolinone a isonitrile.
AB  - A highly stereoselective total synthesis of the alkaloid natural product
      welwitindolinone A isonitrile has been completed. The synthesis utilizes a
      chloronium ion mediated semi-pinacol rearrangement to simultaneously install the
      C10 quaternary center and neopentyl chlorine and a novel anionic cyclization to
      construct the spiro-oxindole with complete stereocontrol.

PMID- 16448106
TI  - Ti coordination in titanium silicalite-1.
AB  - Progressive isomorphous incorporation of TiIV (or BIII) heteroatoms into the MFI
      structure of as-synthesized silicalite-1 caused a decrease in the amount of
      siloxy groups (anions), requisite for counter-balancing the structural directing
      agent (cation), as determined using 1H MAS NMR to quantify the silanol protons H
      bonded to the siloxy oxygen. This revealed the negative charge on the
      incorporated heteroatoms, identifying them as TiO5 (or BO4) sites.

PMID- 16448107
TI  - Iterative, aqueous synthesis of beta3-oligopeptides without coupling reagents.
AB  - The chemoselective synthesis of amides by decarboxylative couplings of alpha
      ketoacids and isoxazolidines makes possible an iterative approach to poly-beta3
      peptides. Peptide assembly occurs under aqueous conditions and requires no
      coupling reagents. The requisite isoxazolidine monomers are prepared in
      enantiopure form by a convenient two-step protocol starting from the appropriate
      aldehydes.

PMID- 16448108
TI  - Axially chiral guanidine as enantioselective base catalyst for 1,4-addition
      reaction of 1,3-dicarbonyl compounds with conjugated nitroalkenes.
AB  - A new strategy for designing chiral guanidine molecules is presented, which
      features the introduction of an axially chiral binaphthyl backbone. The axially
      chiral guanidine catalysts thus developed facilitated the highly enantioselective
      1,4-addition reaction of 1,3-dicarbonyl compounds with a broad range of
      conjugated nitroalkenes and showed extremely high catalytic activity.

PMID- 16448109
TI  - Checkerboard-type charge-ordered state of a pressure-induced superconductor, beta
      (meso-DMBEDT-TTF)2PF6.
AB  - To investigate the insulating state of the pressure-induced superconductor, beta
      (meso-DMBEDT-TTF)2PF6, we have carried out X-ray analysis at 11.5 K. In an
      asymmetric unit, there exist two crystallographically independent donor
      molecules, caused by charge separation. In the column structure, the arrangement
      of the charge-rich (r) and -poor (p) donor molecules is as rrpprrpp, which
      affords "checkerboard"-type charge ordering.

PMID- 16448110
TI  - Multiple C-H bond activation in group 3 chemistry: synthesis and structural
      characterization of an yttrium-aluminum-methine cluster.
AB  - Complete donor-induced alkylaluminate cleavage of halfmetallocene complex
      Cp*Y(AlMe4)2, that is, treatment of Cp*Y(AlMe4)2 with 2 equiv of diethyl ether,
      produces [Cp*Y(mu2-Me)2]3 in high yield (95%). In contrast, the equimolar
      reaction of Cp*Y(AlMe4)2 with diethyl ether reproducibly formed complex
      [Cp*4Y4(mu2-CH3)2{(CH3)Al(mu2-CH3)2}4(mu4-CH)2] in low yield (10-30%) via a
      multiple C-H bond activation. The synthesis of the heterooctametallic yttrium
      aluminum-methine cluster was also accomplished in moderate yield (47%) by the
      equimolar reaction of discrete Cp*Y(AlMe4)2 and [Cp*Y(mu2-Me)2]3 in the absence
      of any donor solvent and "free" AlMe3. This gives strong evidence that preformed
      heterometal-bridged Y-CH3-Al moieties are prone to multiple hydrogen abstraction
      in the presence of a highly basic reagent such as [Cp*Y(mu2-Me)2]3. The
      monocylopentadienyl complexes [Cp*Y(mu2-Me)2]3 and [Cp*4Y4(mu2-CH3)2{(CH3)Al(mu2
      CH3)2}4(mu4-CH)2] were structurally characterized.

PMID- 16448111
TI  - Palladium(II)-catalyzed aerobic dialkoxylation of styrenes: a profound influence
      of an o-phenol.
AB  - We report a Pd(II)-catalyzed aerobic dialkoxylation of styrene derivatives that
      requires an o-phenol. Initial scope and preliminary mechanistic studies are
      presented in which the o-phenol is proposed to facilitate the formation of a
      quinone methide intermediate.

PMID- 16448112
TI  - Macroporous manganese oxides with regenerative mesopores.
AB  - We demonstrate a simple route to making hierarchically porous MnO. Macropores in
      Mn3O4 are induced through a process of powder sintering. The loss of volume
      associated with the reduction of Mn3O4 to MnO results in the formation of
      mesopores in the walls of a macroporous monolith of MnO. The mesopores are
      regenerative, in that oxidation closes them up and reduction opens them again.

PMID- 16448113
TI  - Catalytic four-component assembly based on allenylboronate platform: new access
      to privileged allylic amine structures.
AB  - We developed a novel palladium-catalyzed four-component assembly based on
      allenylboronate platform, by which privileged allylic amine structures can be
      constructed in a regioselective, stereoselective, and diversity-oriented manner.
      The boryl group acts not only as a useful group that can be transformed to
      various functional groups afterward but also as a stereochemical controller in
      the generation of key (pi-allyl)palladium intermediates. A short synthesis of
      rolipram (selective phosphodiesterase-4 inhibitor) is also demonstrated.

PMID- 16448114
TI  - Springs, rings, and spirals of rutile-structured tin oxide nanobelts.
AB  - Single-crystalline springs, rings, and spirals have been discovered for the first
      time in rutile-structured SnO2. The formation process is proposed for minimizing
      the electrostatic energy due to the polar charges on the (011) surfaces. These
      structures are not only ideal systems for fundamental understanding of the
      polarization effect on the morphology at the nanoscale level but also have
      potential applications as nanoscale sensors, resonators, and transducers.

PMID- 16448115
TI  - Photoinduced phase separation.
AB  - A novel approach of photoinduced phase separation has been demonstrated with a
      photolabile anionic surfactant, mixed with an inert nonionic surfactant in the
      presence of salting-out electrolyte. Breakdown of the photolyzable surfactant
      results in hydrophobic photoproducts, which are emulsified by the remaining inert
      surfactant; added electrolyte resolves the emulsion into macroscopic oily and
      aqueous phases. The initial micellar systems can disperse an insoluble additive
      marker dye (shown), which may be spatially segregated from the aqueous
      environment by the action of UV light.

PMID- 16448116
TI  - Iron-assisted vapor-phase hydrothermal method: a low-temperature approach to
      synthesize blue light emissive SiOx nanowires with single-crystal structure of
      P2(1)2(1)2.
AB  - A novel and facile approach, named iron-assisted vapor-phase hydrothermal method,
      is proposed to fabricate the long and stable bright blue light emitting SiOx
      nanowires (SiONWs) at a low temperature. The obtained SiONWs possess a brand-new
      single-crystalline structure of space group P21212. This new type of bright blue
      light emitting SiONW with a new single-crystalline structure may initiate a new
      1D optical material and offer new opportunities for the research in science and
      technology.

PMID- 16448117
TI  - Umpolung of Michael acceptors catalyzed by N-heterocyclic carbenes.
AB  - N-Heterocyclic carbenes can catalyze beta-alkylations of a range of alpha,beta
      unsaturated esters, amides, and nitriles that bear pendant leaving groups to form
      a variety of ring sizes. In this process, the nucleophilic catalyst transiently
      transforms the normally electrophilic beta carbon into a nucleophilic site
      through an unanticipated addition-tautomerization sequence.

PMID- 16448119
TI  - Operating molecular elevators.
AB  - Inspired by the concept of multivalency in living systems, two mechanically
      interlocked molecules have been conceived that incorporate not once or twice but
      thrice the features of a pH-switchable [2]rotaxane with two orthogonal
      recognition sites for dibenzo[24]crown-8 (DB24C8), and 2,3-dinaphtho[24]crown-8
      (DN24C8)-one a dialkylammonium ion (CH(2)NH(2)(+)CH(2)) and the other a
      bipyridinium dication (BIPY(2+)). Whereas at low pH, the CH(2)NH(2)(+)CH(2) sites
      bind the DB24C8/DN24C8 macrocycles preferentially, at high pH, deprotonation
      occurs with loss of hydrogen bonding and the macrocycles will move to the
      BIPY(2+) sites, where they can acquire some stabilizing [pi-pi] stacking
      interactions. Such mechanically interlocked molecules have been assembled from a
      trifurcated rig-like component wherein the dumbbell-like components of three
      [2]rotaxanes have one of their ends fused onto alternate positions (1,3,5) around
      a benzenoid core. The rig is mechanically interlocked by a platform based on a
      tritopic receptor, wherein either three benzo[24]crown-8 or three 2,3
      naphtho[24]crown-8 macrocycles are fused onto a hexaoxatriphenylene core. The
      synthesis of these molecular elevators involves 1:1 complexation, followed by
      stoppering, i.e., feet are added to the rig. (1)H NMR spectroscopy and cyclic
      voltammetry, aided and abetted by absorption spectroscopy, have been employed to
      unravel the details of the mechanism by which the rig and platform components
      move on the alternate addition of base and acid. For each molecular elevator, the
      platform operates by taking three distinct steps associated with each of the
      three deprotonation/reprotonation processes. Thus, molecular elevators are more
      reminiscent of a legged animal than they are of passengers on freight elevators.

PMID- 16448118
TI  - The "somersault" mechanism for the p-450 hydroxylation of hydrocarbons. The
      intervention of transient inverted metastable hydroperoxides.
AB  - A series of model theoretical calculations are described that suggest a new
      mechanism for the oxidation step in enzymatic cytochrome P450 hydroxylation of
      saturated hydrocarbons. A new class of metastable metal hydroperoxides is
      described that involves the rearrangement of the ground-state metal hydroperoxide
      to its inverted isomeric form with a hydroxyl radical hydrogen bonded to the
      metal oxide (MO-OH --> MO....HO). The activation energy for this somersault
      motion of the FeO-OH group is 20.3 kcal/mol for the P450 model porphyrin
      iron(III) hydroperoxide [Por(SH)Fe(III)-OOH(-)] to produce the isomeric ferryl
      oxygen hydrogen bonded to an *OH radical [Por(SH)Fe(III)-O....HO(-)]. This
      isomeric metastable hydroperoxide, the proposed primary oxidant in the P450
      hydroxylation reaction, is calculated to be 17.8 kcal/mol higher in energy than
      the ground-state iron(III) hydroperoxide Cpd 0. The first step of the proposed
      mechanism for isobutane oxidation is abstraction of a hydrogen atom from the C-H
      bond of isobutane by the hydrogen-bonded hydroxyl radical to produce a water
      molecule strongly hydrogen bonded to anionic Cpd II. The hydroxylation step
      involves a concerted but nonsynchronous transfer of a hydrogen atom from this
      newly formed, bound, water molecule to the ferryl oxygen with a concomitant
      rebound of the incipient *OH radical to the carbon radical of isobutane to
      produce the C-O bond of the final product, tert-butyl alcohol. The TS for the
      oxygen rebound step is 2 kcal/mol lower in energy than the hydrogen abstraction
      TS (DeltaE() = 19.5 kcal/mol). The overall proposed new mechanism is consistent
      with a lot of the ancillary experimental data for this enzymatic hydroxylation
      reaction.

PMID- 16448120
TI  - Synthesis and photoelectron spectroscopic studies of N(CH2CH2NMe)3P=E (E = O, S,
      NH, CH2).
AB  - The synthesis and the crystal and molecular structure of
      N(CH(2)CH(2)NMe)(3)P=CH(2) is reported. The P-N(ax) distance is rather long in
      N(CH(2)CH(2)NMe)(3)P=CH(2). The ylide N(CH(2)CH(2)NMe)(3)P=CH(2) proved to be a
      stronger proton acceptor than proazaphosphatrane N(CH(2)CH(2)NMe)(3)P, since it
      was shown to deprotonate N(CH(2)CH(2)NMe)(3)PH(+). The extremely strong basicity
      of the ylide is in accordance with its low ionization energy (6.3 eV), which is
      the lowest in the presently investigated series N(CH(2)CH(2)NMe)(3)P=E (E: CH(2),
      NH, lone pair, O and S), and to the best of our knowledge it is the smallest
      value observed for a non-conjugated phosphorus ylide. Computations reveal the
      existence of two bond strech isomers, and the stabilization of the phosphorus
      centered cation by electron donation from the equatorial and the axial nitrogens.
      Similar stabilizing effects operate in the case of protonation of E. A fine
      balance of these different interactions determines the P-N(ax) distance, which is
      thus very sensitive to the level of the theory applied. According to the quantum
      mechanical calculations, methyl substitution at the equatorial nitrogens flattens
      the pyramidality of this atom, increasing its electron donor capability. As a
      consequence, the PN(ax) distance in the short-transannular bonded protonated
      systems and the radical cations is longer by about 0.5 A in the N(eq)(Me) than in
      the N(eq)(H) systems. Accordingly, isodesmic reaction energies show that a
      stabilization of about 25 and 10 kcal/mol is attributable to the formation of the
      transannular bond in case of N(eq)(H) and the experimentally realizable N(eq)(Me)
      species, respectively.

PMID- 16448121
TI  - Ruthenium molecular wires with conjugated bridging ligands: onset of band
      formation in linear inorganic conjugated oligomers.
AB  - We have prepared and characterized a series of multimetallic oligomers of Ru
      using the pi-conjugated bridging ligand tetra-2-pyridyl-1,4-pyrazine (tppz), as
      well as mixed-ligand complexes with terpyridine end caps, and analyzed their
      electrochemical and spectroscopic properties, comparing them with modern
      computational electronic structure methods. The results suggest that the high
      degree of metal-metal interunit communication in these linear oligomers yields
      low HOMO-LUMO gaps, high delocalization, and the onset of "quasi-band" features,
      all indicative that these compounds should be excellent molecular wire materials.
      Recent spectroscopic and excited-state analyses of these and related compounds
      focus on optically accessible states, which ignore optically silent frontier
      electronic states more relevant to nanoelectronic applications.

PMID- 16448122
TI  - Exploring the energy landscape of a small RNA hairpin.
AB  - The energy landscape of a small RNA tetraloop hairpin is explored by temperature
      jump kinetics and base-substitution. The folding kinetics are single-exponential
      near the folding transition midpoint T(m). An additional fast phase appears below
      the midpoint, and an additional slow phase appears above the midpoint. Stem
      mutation affects the high-temperature phase, while loop mutation affects the low
      temperature phase. An adjusted 2-D lattice model reproduces the temperature
      dependent phases, although it oversimplifies the structural interpretation. A
      four-state free energy landscape model is generated based on the lattice model.
      This model explains the thermodynamics and multiphase kinetics over the full
      temperature range of the experiments. An analysis of three variants shows that
      one of the intermediate RNA structures is a stacking-related trap affected by
      stem but not loop modification, while the other is an early intermediate that
      forms some stem and loop structure. Even a very fast-folding 8-mer RNA with an
      ideal tetraloop sequence has a rugged energy landscape, ideal for testing
      analytical and computational models.

PMID- 16448123
TI  - Selective formation of a self-assembling homo or hetero cavitand cage via metal
      coordination based on thermodynamic or kinetic control.
AB  - The selective formation of a homo or hetero cavitand cage composed of two
      molecules of tetra(4-pyridyl)-cavitand (1), tetrakis(4-cyanophenyl)-cavitand (2),
      or tetrakis(4-pyridylethynyl)-cavitand (3), and four molecules of
      Pd(dppp)(OTf)(2) (4) or Pt(dppp)(OTf)(2) (5) has been studied. A 1:1:4 mixture of
      1 with more steric restriction, 2 with less coordination ability, and 4 or 5
      specifically self-assembled into a hetero cavitand cage 6 or 7, respectively. In
      contrast, a 1:1:4 mixture of 2, 3, and 4 in CDCl(3) at room temperature assembled
      into the most labile homo cyanophenyl cavitand cage 8 and the most stable homo
      pyridylethynyl cavitand cage 9 in a 1:1 ratio. Upon heating at 50 degrees C, the
      thermodynamic equilibrium was shifted to a 1:1:1 mixture of 8, 9, and a hetero
      cavitand cage 10. When 1 equiv of 3 was added to 8 at room temperature, 8, 9, and
      10 were formed initially in a 1:1:3 ratio and finally shifted to a 1:1:1 ratio.
      In the Pt-system, upon addition of 1 equiv of 3 to homo cyanophenyl cavitand cage
      11 in CDCl(3) at room temperature, the ratio of hetero to homo cavitand cage
      (13/12) initially attained was 8.7 and remained above 5.6 at room temperature.
      Upon heating at 50 degrees C, 13 was finally converted to 11 and 12. Thus, the
      selectivity for the self-assembly of the homo or hetero cavitand cage is
      controlled by the balance between kinetic and thermodynamic stabilities of cages
      based on a combination of factors such as coordination ability and steric demand
      of the cavitands.

PMID- 16448124
TI  - Probing the decay coordinate of the green fluorescent protein: arrest of cis
      trans isomerization by the protein significantly narrows the fluorescence
      spectra.
AB  - The fluorescence spectra of the wild-type green fluorescence protein (wt-GFP) and
      the anionic form of p-hydroxybenzylidenedimethylimidazolone (p-HBDI), which
      models the protein chromophore, were obtained in the 80-300 K temperature range
      in glycerol/water solvent. The protein spectra have pronounced and well-resolved
      vibronic structure, at least at lower temperatures. In contrast, the chromophore
      spectra are very broad and structureless even at the lowest temperatures.
      Analysis of the spectra shows that the experimentally observed red-shift of the
      protein spectrum upon heating is apparently caused by quadratic vibronic coupling
      of the torsional deformation (TD) of the phenyl single bond of the chromophore to
      the electronic transition. The broad spectra of the chromophore manifest the
      contribution of different conformations in the glycerol/water solvent. In
      particular, the lowest-temperature spectrum reflects the distribution over the
      same TD coordinate in the excited electronic state, which essentially contributes
      to the asymmetry of the spectrum. Upon heating, motion along this coordinate
      leads to a configuration from which the radiationless transition takes place.
      This narrows the distribution along the TD coordinate, causing a more symmetric
      fluorescence spectrum. We were able to reconstruct the broad, structureless
      fluorescence spectra of p-HBDI in glycerol/water solutions at various
      temperatures by convoluting the original wt-GFP spectra with the function
      describing the distribution of the transition energies of the p-HBDI chromophore.
      Thus, both the fluorescence broadening and increase in radiationless transition
      upon removal of the protein chromophore to bulk solvent are consistent with decay
      by a barrierless TD of the phenyl single bond.

PMID- 16448125
TI  - Characterizing challenging microcrystalline solids with solid-state NMR shift
      tensor and synchrotron X-ray powder diffraction data: structural analysis of
      ambuic acid.
AB  - Synchrotron X-ray powder diffraction and solid-state (13)C NMR shift tensor data
      are combined to provide a unique path to structure in microcrystalline organic
      solids. Analysis is demonstrated on ambuic acid powder, a widely occurring
      natural product, to provide the complete crystal structure. The NMR data verify
      phase purity, specify one molecule per asymmetric unit, and provide an initial
      structural model including relative stereochemistry and molecular conformation. A
      refinement of X-ray data from the initial model establishes that ambuic acid
      crystallizes in the P2(1) space group with unit cell parameters a = 15.5047(7), b
      = 4.3904(2), and c = 14.1933(4) A and beta = 110.3134(3) degrees . This combined
      analysis yields structural improvements at two dihedral angles over prior NMR
      predictions with differences of 103 degrees and 37 degrees found. Only minor
      differences of +/-5.5 degrees , on average, are observed at all remaining
      dihedral angles. Predicted hydroxyl hydrogen-bonding orientations also fit NMR
      predictions within +/-6.9 degrees . This refinement corrects chemical shift
      assignments at two carbons and reduces the NMR error by approximately 16%. This
      work demonstrates that the combination of long-range order information from
      synchrotron powder diffraction data together with the accurate shorter range
      structure given by solid-state NMR measurements is a powerful tool for studying
      challenging organic solids.

PMID- 16448126
TI  - A DFT/CDM Study of metal-carboxylate interactions in metalloproteins: factors
      governing the maximum number of metal-bound carboxylates.
AB  - The number of negatively charged metal-bound Asp/Glu residues determines the net
      charge of the carboxylate-rich metal-binding site, which has been found to play a
      role in enhancing the affinity and/or selectivity of a protein cavity for a given
      metal cofactor. Therefore, it is of interest to know the maximum number of
      carboxylates that could bind to a given metal (M(q)()(+)) of charge q and the key
      factors determining this upper limit in protein cavities, which are usually
      relatively buried. Using density functional theory combined with the continuum
      dielectric method to compute the H(2)O --> CH(3)COO(-) exchange free energies,
      the maximum number of carboxylates bound to M(q)()(+) in a relatively buried
      metal-binding site is found to depend on (i) the metal charge, q, (ii) the
      carboxylate-binding mode, and (iii) the first-shell carboxylate-second-shell
      ligand interactions. The maximum number of carboxylates bound to M(q)()(+) in a
      fully/partially solvent inaccessible protein cavity would not likely exceed q + 2
      if (a) the metal-bound Asp/Glu side chains are hydrogen bonded to a Lys/Arg side
      chain or several peptide backbone amides/Asn/Gln side chains in the metal's
      second coordination shell or (b) at least one acidic residue binds bidentately,
      as opposed to monodentately, to the metal cofactor. This number is reduced to q +
      1 in the absence of stabilizing interactions from outer-shell ligand(s) and if
      all the carboxylates are bound monodentately to the metal cofactor in a buried
      cavity. The computational results are consistent with findings from a PDB survey
      of uni-, di-, and trivalent metal-binding sites containing Asp/Glu residues.

PMID- 16448127
TI  - pH Rate profiles of FnY356-R2s (n = 2, 3, 4) in Escherichia coli ribonucleotide
      reductase: evidence that Y356 is a redox-active amino acid along the radical
      propagation pathway.
AB  - The Escherichia coli ribonucleotide reductase (RNR), composed of two subunits (R1
      and R2), catalyzes the conversion of nucleotides to deoxynucleotides. Substrate
      reduction requires that a tyrosyl radical (Y(122)*) in R2 generate a transient
      cysteinyl radical (C(439)*) in R1 through a pathway thought to involve amino acid
      radical intermediates [Y(122)* --> W(48) --> Y(356) within R2 to Y(731) -->
      Y(730) --> C(439) within R1]. To study this radical propagation process, we have
      synthesized R2 semisynthetically using intein technology and replaced Y(356) with
      a variety of fluorinated tyrosine analogues (2,3-F(2)Y, 3,5-F(2)Y, 2,3,5-F(3)Y,
      2,3,6-F(3)Y, and F(4)Y) that have been described and characterized in the
      accompanying paper. These fluorinated tyrosine derivatives have potentials that
      vary from -50 to +270 mV relative to tyrosine over the accessible pH range for
      RNR and pK(a)s that range from 5.6 to 7.8. The pH rate profiles of
      deoxynucleotide production by these F(n)()Y(356)-R2s are reported. The results
      suggest that the rate-determining step can be changed from a physical step to the
      radical propagation step by altering the reduction potential of Y(356)* using
      these analogues. As the difference in potential of the F(n)()Y* relative to Y*
      becomes >80 mV, the activity of RNR becomes inhibited, and by 200 mV, RNR
      activity is no longer detectable. These studies support the model that Y(356) is
      a redox-active amino acid on the radical-propagation pathway. On the basis of our
      previous studies with 3-NO(2)Y(356)-R2, we assume that 2,3,5-F(3)Y(356), 2,3,6
      F(3)Y(356), and F(4)Y(356)-R2s are all deprotonated at pH > 7.5. We show that
      they all efficiently initiate nucleotide reduction. If this assumption is
      correct, then a hydrogen-bonding pathway between W(48) and Y(356) of R2 and
      Y(731) of R1 does not play a central role in triggering radical initiation nor is
      hydrogen-atom transfer between these residues obligatory for radical propagation.

PMID- 16448128
TI  - Mono-, di-, tri-, and tetra-substituted fluorotyrosines: new probes for enzymes
      that use tyrosyl radicals in catalysis.
AB  - A set of N-acylated, carboxyamide fluorotyrosine (F(n)()Y) analogues [Ac-3-FY
      NH(2), Ac-3,5-F(2)Y-NH(2), Ac-2,3-F(2)Y-NH(2), Ac-2,3,5-F(3)Y-NH(2), Ac-2,3,6
      F(3)Y-NH(2) and Ac-2,3,5,6-F(4)Y-NH(2)] have been synthesized from their
      corresponding amino acids to interrogate the detailed reaction mechanism(s)
      accessible to F(n)()Y*s in small molecules and in proteins. These Ac-F(n)()Y
      NH(2) derivatives span a pK(a) range from 5.6 to 8.4 and a reduction potential
      range of 320 mV in the pH region accessible to most proteins (6-9). DFT
      electronic-structure calculations capture the observed trends for both the
      reduction potentials and pK(a)s. Dipeptides of the methyl ester of 4-benzoyl-l
      phenylalanyl-F(n)()Ys at pH 4 were examined with a nanosecond laser pulse and
      transient absorption spectroscopy to provide absorption spectra of F(n)()Y*s. The
      EPR spectrum of each F(n)()Y* has also been determined by UV photolysis of
      solutions at pH 11 and 77 K. The ability to vary systematically both pK(a) and
      radical reduction potential, together with the facility to monitor radical
      formation with distinct absorption and EPR features, establishes that F(n)()Ys
      will be useful in the study of biological charge-transport mechanisms involving
      tyrosine. To demonstrate the efficacy of the fluorotyrosine method in unraveling
      charge transport in complex biological systems, we report the global substitution
      of tyrosine by 3-fluorotyrosine (3-FY) in the R2 subunit of ribonucleotide
      reductase (RNR) and present the EPR spectrum along with its simulation of 3
      FY122*. In the companion paper, we demonstrate the utility of F(n)()Ys in
      providing insight into the mechanism of tyrosine oxidation in biological systems
      by incorporating them site-specifically at position 356 in the R2 subunit of
      Escherichia coli RNR.

PMID- 16448130
TI  - Aerosol assisted chemical vapor deposition using nanoparticle precursors: a route
      to nanocomposite thin films.
AB  - Gold nanoparticle and gold/semiconductor nanocomposite thin films have been
      deposited using aerosol assisted chemical vapor deposition (CVD). A preformed
      gold colloid in toluene was used as a precursor to deposit gold films onto silica
      glass. These nanoparticle films showed the characteristic plasmon absorption of
      Au nanoparticles at 537 nm, and scanning electron microscopic (SEM) imaging
      confirmed the presence of individual gold particles. Nanocomposite films were
      deposited from the colloid concurrently with conventional CVD precursors. A film
      of gold particles in a host tungsten oxide matrix resulted from co-deposition
      with [W(OPh)(6)], while gold particles in a host titania matrix resulted from co
      deposition with [Ti(O(i)Pr)(4)]. The density of Au nanoparticles within the film
      could be varied by changing the Au colloid concentration in the original
      precursor solution. Titania/gold composite films were intensely colored and
      showed dichromism: blue in transmitted light and red in reflected light. They
      showed metal-like reflection spectra and plasmon absorption. X-ray photoelectron
      spectroscopy and energy-dispersive X-ray analysis confirmed the presence of
      metallic gold, and SEM imaging showed individual Au nanoparticles embedded in the
      films. X-ray diffraction detected crystalline gold in the composite films. This
      CVD technique can be readily extended to produce other nanocomposite films by
      varying the colloids and precursors used, and it offers a rapid, convenient route
      to nanoparticle and nanocomposite thin films.

PMID- 16448131
TI  - Determination of equilibrium constants for atom transfer radical polymerization.
AB  - Atom transfer radical polymerization (ATRP) equilibrium constants (K(ATRP)) were
      determined using modified Fischer's equations for the persistent radical effect.
      The original Fischer's equations could be used only for low conversion of Cu(I)
      to X-Cu(II) and consequently for relatively low values of K(ATRP). At higher
      conversion to X-Cu(II) (>10%) and for larger values of K(ATRP) (>10(-)(7)),
      modified equations that take into account the changes in catalyst and initiator
      concentrations should be used. The validity of new equations was confirmed by
      detailed kinetic simulations. UV-vis spectrometric and GC measurements were used
      to follow the evolution of X-Cu(II) species and the initiator concentration,
      respectively, and to successfully determine values of K(ATRP) for several
      catalysts and alkyl halides. The effect of structure on reactivities of ATRP
      components is presented.

PMID- 16448129
TI  - The A-Fx to F(A/B) step in synechocystis 6803 photosystem I is entropy driven.
AB  - We have previously reported the enthalpy and volume changes of charge separation
      in photosystem I from Synechocystis 6803 using pulsed photoacoustics on the
      microsecond time scale, assigned to the electron-transfer reaction from excited
      state P(700) to F(A/B) iron sulfur clusters. In the present work, we focus on the
      thermodynamics of two steps in photosystem I: (1) P(700) --> A(1)(-)F(X) (<10 ns)
      and (2) A(1)(-)F(X) --> F(A/B)(-) (20-200 ns). The fit by convolution of
      photoacoustic waves on the nanosecond and microsecond time scales resolved two
      kinetic components: (1) a prompt component (<10 ns) with large negative enthalpy
      (-0.8 +/- 0.1 eV) and large volume change (-23 +/- 2 A(3)), which are assigned to
      the P(700) --> A(1)(-)F(X) step, and (2) a component with approximately 200 ns
      lifetime, which has a positive enthalpy (+0.4 +/- 0.2 eV) and a small volume
      change (-3 +/- 2 A(3)) that are attributed to the A(1)(-)F(X) --> F(A/B)(-) step.
      For the fast reaction using the redox potentials of A(1)F(X) (-0.67 V) and P(700)
      (+0.45 V) and the energy of P(700) (1.77 eV), the free energy change for the
      P(700) --> A(1)(-)F(X) step is -0.63 eV, and thus the entropy change (TDeltaS, T
      = 25 degrees C) is -0.2 +/- 0.3 eV. For the slow reaction, A(1)(-)F(X) -->
      F(A/B)(-), taking the free energy of -0.14 eV [Santabara, S.; Heathcote, P;
      Evans, C. W. Biochim. Biophys. Acta 2005, 1708, 283-310], the entropy change
      (TDeltaS) is positive, +0.54 +/- 0.3 eV. The positive entropy contribution is
      larger than the positive enthalpy, which indicates that the A(-)F(X) to F(A/B)(-)
      step in photosystem I is entropy driven. Other possible contributions to the
      measured values are discussed.

PMID- 16448132
TI  - A comprehensive approach to the synthesis of sulfate esters.
AB  - A comprehensive approach to the synthesis of sulfate esters was developed. This
      approach permits the direct and high-yielding synthesis of protected sulfate
      monoesters. Subsequent deblocking to reveal sulfate monoesters is accomplished in
      near-quantitative yield. The exceptionally stable neopentyl protecting group and
      the labile isobutyl protecting group were utilized in the synthesis of aromatic
      and aliphatic sulfate monoesters. Strategies for tuning protecting group
      reactivity were also explored and developed.

PMID- 16448133
TI  - Bismuth-catalyzed intermolecular hydroamination of 1,3-dienes with carbamates,
      sulfonamides, and carboxamides.
AB  - A Bi(OTf)(3)/Cu(CH(3)CN)(4)PF(6) system efficiently promoted intermolecular 1:1
      hydroamination of 1,3-dienes with various carbamates, sulfonamides, and
      carboxamides to afford allylic amines in good yield (up to 96%). Reaction
      proceeded with 0.5-10 mol % catalyst loading at 25-100 degrees C (generally at 50
      degrees C) in 1,4-dioxane within 24 h. The Bi(OTf)(3)/Cu(CH(3)CN)(4)PF(6) system
      constitutes a new entry into series of intermolecular hydroamination catalysis.
      Mechanistic studies and the postulated reaction mechanism are also discussed.

PMID- 16448134
TI  - Substrate specificity of an active dinuclear Zn(II) catalyst for cleavage of RNA
      analogues and a dinucleoside.
AB  - The cleavage of the diribonucleoside UpU (uridylyl-3'-5'-uridine) to form uridine
      and uridine (2',3')-cyclic phosphate catalyzed by the dinuclear Zn(II) complex of
      1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(1)(H(2)O)) has been
      studied at pH 7-10 and 25 degrees C. The kinetic data are consistent with the
      accumulation of a complex between catalyst and substrate and were analyzed to
      give values of k(c) (s(-)(1)), K(d) (M), and k(c)/K(d) (M(-)(1) s(-)(1)) for the
      Zn(2)(1)(H(2)O)-catalyzed reaction. The pH rate profile of values for log
      k(c)/K(d) for Zn(2)(1)(H(2)O)-catalyzed cleavage of UpU shows the same downward
      break centered at pH 7.8 as was observed in studies of catalysis of cleavage of 2
      hydroxypropyl-4-nitrophenyl phosphate (HpPNP) and uridine-3'-4-nitrophenyl
      phosphate (UpPNP). At low pH, where the rate acceleration for the catalyzed
      reaction is largest, the stabilizing interaction between Zn(2)(1)(H(2)O) and the
      bound transition states is 9.3, 7.2, and 9.6 kcal/mol for the catalyzed reactions
      of UpU, UpPNP, and HpPNP, respectively. The larger transition-state stabilization
      for Zn(2)(1)(H(2)O)-catalyzed cleavage of UpU (9.3 kcal/mol) compared with UpPNP
      (7.2 kcal/mol) provides evidence that the transition state for the former
      reaction is stabilized by interactions between the catalyst and the C-5'-oxyanion
      of the basic alkoxy leaving group.

PMID- 16448135
TI  - Marinomycins A-D, antitumor-antibiotics of a new structure class from a marine
      actinomycete of the recently discovered genus "marinispora".
AB  - Four antitumor-antibiotics of a new structure class, the marinomycins A-D (1-4),
      were isolated from the saline culture of a new group of marine actinomycetes, for
      which we have proposed the name "Marinispora". The structures of the
      marinomycins, which are unusual macrodiolides composed of dimeric 2-hydroxy-6
      alkenyl-benzoic acid lactones with conjugated tetraene-pentahydroxy polyketide
      chains, were assigned by combined spectral and chemical methods. In room light,
      marinomycin A slowly isomerizes to its geometrical isomers marinomycins B and C.
      Marinomycins A-D show significant antimicrobial activities against drug resistant
      bacterial pathogens and demonstrate impressive and selective cancer cell
      cytotoxicities against six of the eight melanoma cell lines in the National
      Cancer Institute's 60 cell line panel. The discovery of these new compounds from
      a new, chemically rich genus further documents that marine actinomycetes are a
      significant resource for drug discovery.

PMID- 16448136
TI  - NMR structure and dynamic studies of an anion-binding, channel-forming
      heptapeptide.
AB  - The synthetic peptide (C(18)H(37))(2)NCOCH(2)OCH(2)CON-(Gly)(3)-Pro-(Gly)(3)
      OCH(2)Ph forms chloride-selective channels in liposomes and exhibits voltage
      gating properties in planar phospholipid bilayers. The peptide fragment of the
      channel is based on a conserved motif in naturally occurring chloride
      transporters. Membrane-anchoring residues at the N- and C-terminal ends augment
      the peptide. NMR spectra (1D and 2D) of the channel in CDCl(3) showed significant
      variation in the absence and presence of stoichiometric tetrabutylammonium
      chloride (Bu(4)NCl). One-dimensional solution-state NMR titration studies
      combined with computational molecular simulation studies indicate that the
      peptide interacts with the salt as an ion pair and H-bonds chloride. To our
      knowledge, this is the first structural analysis of any synthetic anion-channel
      salt complex.

PMID- 16448138
TI  - Double-ink dip-pen nanolithography studies elucidate molecular transport.
AB  - We have investigated the transport mechanism of the inks most typically used in
      dip-pen nanolithography by patterning both 16-mercaptohexadecanoic acid (MHDA)
      and 1-octadecanethiol (ODT) on the same Au{111} substrate. Several pattern
      geometries were used to probe ink transport from the tip to the sample during
      patterning of both dots (stationary tip) and lines (moving tip). When ODT was
      written on top of a pre-existing MHDA structure, the ODT was observed at the
      outsides of the MHDA structure, and the transport rate increased. In the reverse
      case, the MHDA was also observed on the outsides of the previously patterned ODT
      features; however, the transport rate was reduced. Furthermore, the shapes of pre
      existing patterns of one ink were not changed by deposition of the other ink.
      These results highlight the important role hydrophobicity plays, both of the
      substrate as well as of the inks, in determining transport properties and thereby
      patterns produced in dip-pen nanolithography.

PMID- 16448137
TI  - Rotational and translational diffusion of peptide-coated CdSe/CdS/ZnS nanorods
      studied by fluorescence correlation spectroscopy.
AB  - CdSe/CdS/ZnS nanorods (NRs) of three aspect ratios were coated with phytochelatin
      related peptides and studied using fluorescence correlation spectroscopy (FCS).
      Theoretical predictions of the NRs' rotational diffusion contribution to the
      correlation curves were experimentally confirmed. We monitored rotational and
      translational diffusion of NRs and extracted hydrodynamic radii from the
      extracted diffusion constants. Translational and rotational diffusion constants
      (D(trans) and D(rot)) for NRs were in good agreement with Tirado and Garcia de la
      Torre's as well as with Broersma's theories when accounting for the ligand
      dimensions. NRs fall in the size range where rotational diffusion can be
      monitored with higher sensitivity than translational diffusion due to a steeper
      length dependence, D(rot) approximately L(-)(3) versus D(trans) approximately L(
      )(1). By titrating peptide-coated NRs with bovine serum albumin, we monitored
      (nonspecific) binding through rotational diffusion and showed that D(rot) is an
      advantageous observable for monitoring binding. Monitoring rotational diffusion
      of bioconjugated NRs using FCS might prove to be useful for observing binding and
      conformational dynamics in biological systems.

PMID- 16448139
TI  - The chemistry of dinuclear analogues of the anticancer drug cisplatin. A DFT/CDM
      study.
AB  - The mechanism of the formation of dinuclear platinum(II) mu-hydroxo complexes
      from cisplatin hydrolysis products, their interconversion, decomposition, and
      reactions with biomolecules has been explored using a combined DFT/CDM approach.
      All activation barriers for the formation of [cis-{Pt(NH(3))(2)(X)}-(mu-OH)-cis
      {Pt(NH(3))(2)(Y)}](n)()(+) (X, Y = Cl, OH(2), OH) via nucleophilic attack of a
      hydroxo complex on an aqua complex are lower than the activation barriers for
      cisplatin hydrolysis. Considering therapeutic Pt(II) concentrations in tumors,
      however, only the reaction between two molecules of cis
      [Pt(NH(3))(2)(OH(2))(OH)](+) (E) yielding [cis-{Pt(NH(3))(2)(OH(2))}-(mu-OH)-cis
      {Pt(NH(3))(2)(OH)}](2+) (5) remains kinetically superior to cisplatin hydrolysis.
      5 is strongly stabilized by intramolecular hydrogen bonding between the terminal
      aqua and hydroxo ligands, resulting in an unusually high pK(a) of 5 and a low
      pK(a) of its conjugate acid. Unimolecular cyclization of 5 yields the dimers [cis
      {Pt(NH(3))(2)}(mu-OH)](2)(2+) (7a with antiperiplanar OH groups and 7b with
      synperiplanar OH groups). The electronic structure of several diplatinum(II)
      complexes has been analyzed to clarify whether there are metal-metal
      interactions. The overall reactivity to guanine (Gua) and dimethyl sulfide (Met,
      representing the thioether functional group of methionine) increases in the order
      5 < 7a approximately 7b < mononuclear complexes, whereas the kinetic selectivity
      to Gua relative to Met increases in the order 7a approximately 5 < 7b
      approximately monocationic mononuclear complexes < dicationic mononuclear
      complex. The results of this work (i) help assess whether dinuclear metabolites
      play a role in cisplatin chemotherapy, (ii) elucidate the toxicity and
      pharmacological inactivity of [cis-{Pt(NH(3))(2)}(mu-OH)](2)(2+), and (iii)
      suggest future investigations of dinuclear anticancer complexes that contain one
      mu-hydroxo ligand.

PMID- 16448140
TI  - Design of highly active binary catalyst systems for CO2/epoxide copolymerization:
      polymer selectivity, enantioselectivity, and stereochemistry control.
AB  - Asymmetric, regio- and stereoselective alternating copolymerization of CO(2) and
      racemic aliphatic epoxides proceeds effectively under mild temperature and
      pressure by using a binary catalyst system of a chiral tetradentate Schiff base
      cobalt complex [SalenCo(III)X] as the electrophile in conjunction with an ionic
      organic ammonium salt or a sterically hindered strong organic base as the
      nucleophile. The substituent groups on the aromatic rings, chiral diamine
      backbone, and axial X group of the electrophile, as well as the nucleophilicity,
      leaving ability, and coordination ability of the nucleophile, all significantly
      affect the catalyst activity, polymer selectivity, enantioselectivity, and
      stereochemistry. A bulky chiral cyclohexenediimine backbone complex
      [SalcyCo(III)X] with an axial X group of poor leaving ability as the
      electrophile, combined with a bulky nuclephile with poor leaving ability and low
      coordination ability, is an ideal binary catalyst system for the copolymerization
      of CO(2) and a racemic aliphatic epoxide to selectively produce polycarbonates
      with relatively high enantioselectivity, >95% head-to-tail connectivity, and >99%
      carbonate linkages. A fast copolymerization of CO(2) and epoxides was observed
      when the concentration of the electrophile or/and the nucleophile was increased,
      and the number of polycarbonate chains was proportional to the concentration of
      the nucleophile. Electrospray ionization mass spectrometry, in combination with a
      kinetic study, showed that the copolymerization involved the coordination
      activation of the monomer by the electrophile and polymer chain growth
      predominately occurring in the nucleophile. Both the enantiomorphic site effect
      resulting from the chiral electrophile and the polymer chain end effect mainly
      from the bulky nucleophile cooperatively control the stereochemistry of the
      CO(2)/epoxide copolymerization.

PMID- 16448141
TI  - The concept of delayed nucleation in nanocrystal growth demonstrated for the case
      of iron oxide nanodisks.
AB  - A comprehensive study of iron oxide nanocrystal growth through non-hydrolitic,
      surfactant-mediated thermal reaction of iron pentacarbonyl and an oxidizer has
      been conducted, which includes size control, anisotropic shape evolution, and
      crystallographic phase transition of monodisperse iron oxide colloidal
      nanocrystals. The reaction was monitored via in situ UV-vis spectroscopy, taking
      advantage of the color change accompanying the iron oxide colloid formation,
      allowing measurement of the induction time for nucleation. Features of the
      synthesis such as the size control and reproducibility are related to the
      occurrence of the observed delayed nucleation process. As a separate source of
      iron and oxygen is adopted, phase control could also be achieved by sequential
      injections of oxidizer.

PMID- 16448142
TI  - Effect of single-point sequence alterations on the aggregation propensity of a
      model protein.
AB  - Sequences of contemporary proteins are believed to have evolved through a process
      that optimized their overall fitness, including their resistance to deleterious
      aggregation. Biotechnological processing may expose therapeutic proteins to
      conditions that are much more conducive to aggregation than those encountered in
      a cellular environment. An important task of protein engineering is to identify
      alternative sequences that would protect proteins when processed at high
      concentrations without altering their native structure associated with specific
      biological function. Our computational studies exploit parallel tempering
      simulations of coarse-grained model proteins to demonstrate that isolated amino
      acid residue substitutions can result in significant changes in the aggregation
      resistance of the protein in a crowded environment while retaining protein
      structure in isolation. A thermodynamic analysis of protein clusters subject to
      competing processes of folding and association shows that moderate mutations can
      produce effects similar to those caused by changes in system conditions,
      including temperature, concentration, and solvent composition, that affect the
      aggregation propensity. The range of conditions where a protein can resist
      aggregation can therefore be tuned by sequence alterations, although the protein
      generally may retain its generic ability for aggregation.

PMID- 16448143
TI  - Polymer crystallization-driven, periodic patterning on carbon nanotubes.
AB  - We report herein a unique means to periodically pattern polymeric materials on
      individual carbon nanotubes (CNTs) using a controlled polymer crystallization
      method. One-dimensional (1D) CNTs were periodically decorated with polymer
      lamellar crystals, resulting in nano-hybrid shish-kebab (NHSK) structures. The
      periodicity of the polymer lamellae varies from 20 to 150 nm. The kebabs are
      approximately 5-10 nm thick (along CNT direction) with a lateral size of
      approximately 20 nm to micrometers, which can be readily controlled by varying
      crystallization conditions. Both polyethylene and Nylon 66 were successfully
      decorated on single-walled carbon nanotubes (SWNTs), multiwalled carbon nanotubes
      (MWNTs), as well as vapor grown carbon nanofibers (CNFs). The formation mechanism
      was attributed to "size-dependent soft epitaxy". Because NHSK formation
      conditions depend on CNT structures, it further provides a unique opportunity for
      CNT separation. The reported method opens a gateway to periodically patterning
      polymers and different functional groups on individual CNTs in an ordered and
      controlled manner, an attractive research field that is yet to be explored.

PMID- 16448144
TI  - Relationship between two-photon absorption and the pi-conjugation pathway in
      porphyrin arrays through dihedral angle control.
AB  - Recently, covalently linked or self-assembled porphyrin array systems have
      attracted much attention for their enhanced two-photon absorption (TPA)
      behaviors. In this study, we have investigated the TPA properties of various
      dihedral angle controlled, directly linked porphyrin dimers and arrays to
      elucidate the relationship between the pi-conjugation pathway and TPA properties.
      We have demonstrated a strong correlation between pi-conjugation (aromaticity)
      and TPA properties in porphyrin assemblies.

PMID- 16448145
TI  - Toward single molecule DNA sequencing: direct identification of ribonucleoside
      and deoxyribonucleoside 5'-monophosphates by using an engineered protein nanopore
      equipped with a molecular adapter.
AB  - Individual nucleic acid molecules might be sequenced by the identification of
      nucleoside 5'-monophosphates as they are released by processive exonucleases.
      Here, we show that single molecule detection with a modified protein nanopore can
      be used to identify ribonucleoside and 2'-deoxyribonucleoside 5'-monophosphates,
      thereby taking a step along this path. Distinct levels of current block are
      observed for each of the four members of a set of nucleoside 5'-monophosphates
      when the molecules bind within a mutant alpha-hemolysin pore, (M113R)(7),
      equipped with the molecular adapter heptakis-(6-deoxy-6-amino)-beta-cyclodextrin.
      While our results compare favorably with alternative approaches, further work
      will be required to improve the accuracy of identification of the nucleic acid
      bases, to feed each released nucleotide into the pore, and to ensure that every
      nucleotide is captured by the adapter.

PMID- 16448147
TI  - Utilization of the pleiotropy of a peptidic aptamer to fabricate heterogeneous
      nanodot-containing multilayer nanostructures.
AB  - Peptide aptamers (=binders) against inorganic materials often show a capacity for
      mineralization of their target atoms; thus they are able to function both as
      binding molecules and as mediators for mineralization. Although the mechanisms
      underlying these two properties of peptide aptamers are not yet fully understood,
      they have been used separately to fabricate various nanostructures. Here, we
      present a novel method of nanofabrication, in which binding and mineralization by
      a peptide aptamer are alternately utilized to assemble multilayered
      nanostructures comprised of metal loaded cage proteins ornamented with Ti-binding
      peptides.

PMID- 16448146
TI  - Redox enzymes in tethered membranes.
AB  - An electrode surface is presented that enables the characterization of redox
      active membrane enzymes in a native-like environment. An ubiquinol oxidase from
      Escherichia coli, cytochrome bo(3) (cbo(3)), has been co-immobilized into
      tethered bilayer lipid membranes (tBLMs). The tBLM is formed on gold surfaces
      functionalized with cholesterol tethers which insert into the lower leaflet of
      the membrane. The planar membrane architecture is formed by self-assembly of
      proteoliposomes, and its structure is characterized by surface plasmon resonance
      (SPR), electrochemical impedance spectroscopy (EIS), and tapping-mode atomic
      force microscopy (TM-AFM). The functionality of cbo(3) is investigated by cyclic
      voltammetry (CV) and is confirmed by the catalytic reduction of oxygen.
      Interfacial electron transfer to cbo(3) is mediated by the membrane-localized
      ubiquinol-8, the physiological electron donor of cbo(3). Enzyme coverages
      observed with TM-AFM and CV coincide (2-8.5 fmol.cm(-)(2)), indicating that most
      if not all-cbo(3) on the surface is catalytically active and thus retains its
      integrity during immobilization.

PMID- 16448148
TI  - A comprehensive study of self-assembled monolayers of anthracenethiol on gold:
      solvent effects, structure, and stability.
AB  - The formation and molecular structure of self-assembled monolayers (SAMs) of
      anthracene-2-thiol (AnT) on Au(111) have been characterized by reflection
      adsorption infrared spectroscopy, thermal desorption spectroscopy, X-ray
      photoelectron spectroscopy, near-edge X-ray absorption spectroscopy, scanning
      tunneling microscopy, and low energy electron diffraction. It is demonstrated
      that highly ordered monolayer films are formed upon immersion, but their quality
      depends critically on the choice of solvents and rinsing conditions. The
      saturated monolayer is characterized by a closed packed arrangement of upright
      standing molecules forming a (2 x 4)rect unit cell. At about 450 K a partial
      desorption takes place and the remaining molecules form a dilute (4 x 2)-phase
      with an almost planar adsorption geometry, while further heating above 520 K
      causes a thermally induced fragmentation. According to their different densities
      both phases reveal very diverse chemical reactivities. Whereas the saturated
      monolayer is stable and inert under ambient conditions, the dilute phase does not
      warrant any protection of the sulfur headgroups which oxidize rapidly in air.

PMID- 16448149
TI  - A threaded loop conformation adopted by a family of peptoid nonamers.
AB  - Non-natural polymers with well-defined three-dimensional folds offer considerable
      potential for engineering novel functions that are outside the scope of
      biological polymers. Here we describe a family of N-substituted glycine or
      "peptoid" nonamers that folds into an unusual "threaded loop" structure of
      exceptional thermal stability and conformational homogeneity in acetonitrile. The
      structure is chain-length-specific and relies on bulky, chiral side chains and
      chain-terminating functional groups for stability. Notable elements of the
      structure include the engagement of the positively charged amino terminus by
      carbonyl groups of the backbone through hydrogen bonding interactions and
      shielding of polar groups from and near-complete exposure of hydrophobic groups
      to solvent, in a manner resembling a folded polypeptide globular domain turned
      inside-out. The structure is stable in a variety of organic solvents but is
      readily denatured in any solvent/cosolvent milieu with hydrogen bonding
      potential. The structure could serve as a scaffold for the elaboration of novel
      functions and could be used to test methodologies for predicting solvent
      dependent polymer folding.

PMID- 16448150
TI  - Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under
      physiological conditions.
AB  - The Os(II) arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z
      = BPh(4) (4) and BF(4) (5), are inactive toward A2780 ovarian cancer cells
      despite 4 being isostructural with an active Ru(II) analogue, 4R. Hydrolysis of 5
      occurred 40 times more slowly than 4R. The aqua adduct 5A has a low pK(a) (6.3)
      compared to that of [(eta(6)-biphenyl)Ru(en)(OH(2))](2+) (7.7) and is therefore
      largely in the hydroxo form at physiological pH. The rate and extent of reaction
      of 5 with 9-ethylguanine were also less than those of 4R. We replaced the neutral
      en ligand by anionic acetylacetonate (acac). The complexes [(eta(6)
      arene)Os(acac)Cl], arene = biphenyl (6), benzene (7), and p-cymene (8), adopt
      piano-stool structures similar to those of the Ru(II) analogues and form weak
      dimers through intermolecular (arene)C-H...O(acac) H-bonds. Remarkably, these
      Os(II) acac complexes undergo rapid hydrolysis to produce not only the aqua
      adduct, [(eta(6)-arene)Os(acac)(OH(2))](+), but also the hydroxo-bridged dimer,
      [(eta(6)-arene)Os(mu(2)-OH)(3)Os(eta(6)-arene)](+). The pK(a) values for the aqua
      adducts 6A, 7A, and 8A (7.1, 7.3, and 7.6, respectively) are lower than that for
      [(eta(6)-p-cymene)Ru(acac)(OH(2))](+) (9.4). Complex 8A rapidly forms adducts
      with 9-ethylguanine and adenosine, but not with cytidine or thymidine. Despite
      their reactivity toward nucleobases, complexes 6-8 were inactive toward A549 lung
      cancer cells. This is attributable to rapid hydrolysis and formation of
      unreactive hydroxo-bridged dimers which, surprisingly, were the only species
      present in aqueous solution at biologically relevant concentrations. Hence, the
      choice of chelating ligand in Os(II) (and Ru(II)) arene complexes can have a
      dramatic effect on hydrolysis behavior and nucleobase binding and provides a
      means of tuning the reactivity and the potential for discovery of anticancer
      complexes.

PMID- 16448151
TI  - Electrochemical growth of highly oriented organic-inorganic superlattices using
      solid-supported multilamellar membranes as templates.
AB  - Controllable depositing of relatively thick inorganic sublayers into organic
      templates to fabricate organic-inorganic superlattices is of great importance. We
      report a novel approach to fabricating phospholipid/Ni(OH)(2) superlattices by
      electrochemical deposition of the inorganic component into solid-supported
      multilamellar templates. The well-ordered and highly oriented multilamellar
      templates are produced by spreading small drops of lipid solution on silicon
      surfaces and letting the solvent evaporate slowly. The templates which are used
      as working electrodes preserve the lamellar structure in the electrolyte
      solution. The resulting superlattices are highly oriented. The thickness of the
      nickel hydroxide is controlled by the concentration of nickel ions in the
      electrolyte bath. The electron density profiles derived from the X-ray
      diffraction data reveal that the thickness of the nickel hydroxide sublayers
      increases from 15 to 27 A as the concentration of nickel nitrate increases from
      0.005 mol/L to 0.08 mol/L. We expect that the new method can be extended to
      depositing a variety of inorganic components including metals, oxides, and
      semiconductors.

PMID- 16448153
TI  - Aliphatic/aromatic polyimide ionomers as a proton conductive membrane for fuel
      cell applications.
AB  - To produce a proton conductive and durable polymer electrolyte membrane for fuel
      cell applications, a series of sulfonated polyimide ionomers containing aliphatic
      groups both in the main and in the side chains have been synthesized. The title
      polyimide ionomers 1 with the ion exchange capacity of 1.78-2.33 mequiv/g were
      obtained by a typical polycondensation reaction as transparent, ductile, and
      flexible membranes. The proton conductivity of 1 was slightly lower than that of
      the perfluorinated ionomer (Nafion) below 100 degrees C, but comparable at higher
      temperature and 100% RH. The highest conductivity of 0.18 S cm(-)(1) was obtained
      for 1 at 140 degrees C. Ionomer 1 with high IEC and branched chemical structure
      exhibited improved proton conducting behavior without sacrificing membrane
      stability. Microscopic analyses revealed that smaller (<5 nm) and well-dispersed
      hydrophilic domains contribute to better proton conducting properties. Hydrogen
      and oxygen permeability of 1 was 1-2 orders of magnitude lower than that of
      Nafion under both dry and wet conditions. Fuel cell was fabricated with 1
      membrane and operated at 80 degrees C and 0.2 A/cm(2) supplying H(2) and air both
      at 60% or 90% RH. Ionomer 1 membrane showed comparable performance to Nafion and
      was durable for 5000 h without distinct degradation.

PMID- 16448152
TI  - Controlled clustering of superparamagnetic nanoparticles using block copolymers:
      design of new contrast agents for magnetic resonance imaging.
AB  - When polyelectrolyte-neutral block copolymers are mixed in aqueous solutions with
      oppositely charged species, stable complexes are found to form spontaneously. The
      mechanism is based on electrostatics and on the compensation between the opposite
      charges. Electrostatic complexes exhibit a core-shell microstructure. In the
      core, the polyelectrolyte blocks and the oppositely charged species are tightly
      bound and form a dense coacervate microphase. The shell is made of the neutral
      chains and surrounds the core. In this paper, we report on the structural and
      magnetic properties of such complexes made from 6.3 nm diameter superparamagnetic
      nanoparticles (maghemite gamma-Fe(2)O(3)) and cationic-neutral copolymers. The
      copolymers investigated are poly(trimethylammonium ethylacrylate methyl sulfate)
      b-poly(acrylamide), with molecular weights 5000-b-30000 g mol(-)(1) and 110000-b
      30000 g mol(-)(1). The mixed copolymer-nanoparticle aggregates were characterized
      by a combination of light scattering and cryo-transmission electron microscopy.
      Their hydrodynamic diameters were found in the range 70-150 nm, and their
      aggregation numbers (number of nanoparticles per aggregate) from tens to
      hundreds. In addition, Magnetic Resonance Spin-Echo measurements show that the
      complexes have a better contrast in Magnetic Resonance Imaging than single
      nanoparticles and that these complexes could be used for biomedical applications.

PMID- 16448156
TI  - The maize primary cell wall microfibril: a new model derived from direct
      visualization.
AB  - Understanding the molecular architecture of the plant cell wall is critical to
      reducing the biomass recalcitrance problem, which currently impedes economic
      bioconversion processing. The parenchyma cell walls from field senesced, maize
      stem pith have been directly visualized without extraction processes using high
      resolution atomic force microscopy (AFM). By imaging the cell wall inner surfaces
      from different cells and different faces of the same cell, we were able to map
      the native primary cell wall ultrastructures. Depending on the thickness of non
      cellulosic deposition, the parallel-microfibrils appear in various morphologies
      ranging from clearly defined to completely embedded in the wall matrixes forming
      cell wall lamella. Macrofibrils were found to exist only on the uppermost layer
      of the native primary cell wall and appeared to be bundles of elementary fibrils.
      This novel observation led us to a new hypothesis for the cell wall fibrillar
      network and biosynthesis processes. Put concisely, a number of elementary fibrils
      are synthesized at one locus, that of the cellulose synthase complex (CelS), and
      coalesce into much larger macrofibrils. These macrofibrils eventually split at
      the ends to form parallel microfibrils with deposition of other cell wall
      components (i.e. hemicelluloses, pectin, etc.) also evident. On the basis of
      these AFM surface measurements and current supportive evidence from cell wall
      biophysics, biosynthesis, and genomics, we propose a new molecular model
      consisting of a 36-glucan-chain elementary fibril, in which the 36-glucan chains
      form both crystalline and subcrystalline structures. We also propose a modified
      model of CelS based on recently reported experimental evidence from plant cell
      wall biosynthesis.

PMID- 16448158
TI  - Novel fluorometric assay for hydroxyl radical scavenging capacity (HOSC)
      estimation.
AB  - A novel fluorometric method was developed and validated for hydroxyl radical
      scavenging capacity (HOSC) estimation using fluorescein as the probe. A constant
      flux of pure hydroxyl radical is generated under physiological pH using a Fenton
      like Fe3+/H2O2 reaction. The generation of pure hydroxyl radicals under the
      experimental conditions was evaluated and confirmed using electron spin resonance
      with DMPO spin-trapping measurements. The hydroxyl radical scavenging capacity of
      a selected antioxidant sample is quantified by measuring the area under the
      fluorescence decay curve with or without the presence of the antioxidant and
      expressed as Trolox equivalents per unit of the antioxidant. The assay may be
      performed using a plate reader with a fluorescence detector for high-throughput
      measurements. The assay was validated for linearity, precision, accuracy,
      reproducibility, and its correlation with a popular peroxyl radical scavenging
      capacity assay using selected pure antioxidant compounds and botanical extracts.
      This method may provide researchers in the food, nutrition, and medical fields an
      easy to use protocol to evaluate free radical scavenging capacity of pure
      antioxidants and natural extracts in vitro against the very reactive hydroxyl
      radical, which may be linked to numerous degenerative diseases and conditions.

PMID- 16448157
TI  - Determination of total content of phenolic compounds and their antioxidant
      activity in vegetables--evaluation of spectrophotometric methods.
AB  - This research studies in detail the contents of phenolic compounds determined by
      the Folin-Ciocalteu reagent and the antioxidant activities determined by the TEAC
      (Trolox equivalent antioxidant capacity), DPPH (using diphenyl-p-picrylhydrazyl
      radical), and FRAP (ferric reducing antioxidant power) methods, and their
      correlations for used standards with these methods (catechine, gallic acid,
      caffeic acid, ferulic acid, Trolox, ascorbic acid, and ferrous sulfate) and
      extracts from several species of commonly consumed vegetables were studied in
      detail. The comparison of absolute values of absorption coefficients for used
      standards and for individual methods allows one to choose optimal common
      standards for methods to be compared. The procedures applied for the same sets of
      the extracts using identical calibration procedures and common standards allowed
      better comparison of the results obtained by the TEAC, DPPH, and FRAP methods.
      The values of content of phenolic substances and total antioxidant activity of
      the sets of samples correlate very well for all used methods. The very high
      values of antioxidant activity were found in intensely colored vegetables (red
      cabbage, red onion, etc.), and the values were very low in watery vegetables such
      as potato, marrow, and cucumber.

PMID- 16448159
TI  - Ethanol/Water extraction combined with solid-phase extraction and solid-phase
      microextraction concentration for the determination of chlorophenols in cork
      stoppers.
AB  - The appearance of 2,4,6-trichloroanisole (TCA) in cork stoppers is of great
      concern because it can cause off-flavors in bottled wine. To prevent this
      sensorial defect, there should not be any traces of 2,4,6-trichlorophenol (TCP),
      2,3,4,6-tetrachlorophenol (TeCP), or pentachlorophenol (PCP) in the finished
      corks, because they are the direct precursors of TCA. In the course of this study
      two methodologies based upon an extraction with ethanol/water mixtures to
      determine the chlorophenolic content in cork matrices were developed. The cork
      extract is preconcentrated using both solid-phase extraction and solid-phase
      microextraction methodologies. The latter was optimized by applying a full two
      level factorial design. Finally, spiked ground corks at nanogram per gram levels
      of each chlorophenol were analyzed under optimal conditions and by applying both
      procedures. The obtained results demonstrate that chlorophenols can be detected
      in corks contaminated at the nanogram per gram level and, thus, these approaches
      can be successfully applied as quality control measures in the cork industry.

PMID- 16448160
TI  - HPLC analysis of sesaminol glucosides in sesame seeds.
AB  - An HPLC method was developed and validated for the quantification of sesaminol
      triglucoside and a sesaminol diglucoside in sesame seeds. These two lignans were
      isolated, and their structures were characterized by mass and nuclear magnetic
      resonance spectroscopy. Defatted sesame flour was extracted first with 85%
      ethanol for 5 h followed by 70% ethanol for 10 h at room temperature using
      naringenin as internal standard. Analysis of 65 different samples of sesame seeds
      indicated that the content of sesaminol triglucoside ranged from 36 to 1560
      mg/100 g of seed (mean 637 +/- 312) and that of sesaminol diglucoside ranged from
      0 to 493 mg/100 g of seed (mean 75 +/- 95). No significant difference was found
      between sesaminol glucoside contents in black and white seeds.

PMID- 16448161
TI  - Development of a fast analytical method for the determination of sudan dyes in
      chili- and curry-containing foodstuffs by high-performance liquid chromatography
      photodiode array detection.
AB  - A simple and fast analytical method for the determination of sudans I, II, III,
      and IV in chili- and curry-containing foodstuffs is described. These dyes are
      extracted from the samples with acetonitrile and analyzed by high-performance
      liquid chromatography coupled to a photodiode array detector. The chromatographic
      separation is carried out on a reverse phase C18 column with an isocratic mode
      using a mixture of acetonitrile and water. An "in-house" validation was achieved
      in chili- and curry-based sauces and powdered spices. Depending on the dye,
      limits of detection range from 0.2 to 0.5 mg/kg in sauces and from 1.5 to 2 mg/kg
      in spices. Limits of quantification are between 0.4 and 1 mg/kg in sauces and
      between 3 and 4 mg/kg in spices. Validation data show a good repeatability and
      within-lab reproducibility with relative standard deviations < 15%. The overall
      recoveries are in the range of 51-86% in sauces and in the range of 89-100% in
      powdered spices depending on the dye involved. Calibration curves are linear in
      the 0-5 mg/kg range for sauces and in the 0-20 mg/kg range for spices. The
      proposed method is specific and selective, allowing the analysis of over 20
      samples per working day.

PMID- 16448162
TI  - Semiautomated determination of pesticides in water using solid phase extraction
      disks and gas chromatography-mass spectrometry.
AB  - A method based on semiautomated solid phase extraction using octadecyl-bonded
      silica disks and gas chromatography-mass spectrometry, operated in selected ion
      monitoring mode, allows detection and quantification of approximately 100
      pesticides and transformation products in drinking water. Samples (500 mL) were
      passed through the disk, and the retained pesticides were eluted with acetone and
      ethyl acetate. Typical recoveries for pesticides at 0.1 microg L(-1) in water
      were in the range of 72-120% with relative standard deviations less than 20%.
      Calibration curves were linear over the range of 0.025-0.5 microg mL(-1)
      (equivalent to a concentration range in drinking water of 0.05-1.0 microg L(-1)).

PMID- 16448163
TI  - Development of continuous type apparatus for ampholyte-free isoelectric focusing
      (autofocusing) of peptides in protein hydrolysates.
AB  - An apparatus for continuous fractionation of peptides on the basis of amphoteric
      nature of sample peptides was developed. A tank (66.5 cm x 8 cm x 8 cm, L x W x
      H) was divided into 12 compartments by a thin agarose gel layer. A drain tube
      (5.5 cm in length and 0.7 cm in i.d.) was fixed through the bottom of each
      compartment to give a height of 4 cm from the bottom. The tank with 12
      compartments and electrodes was referred to as an autofocusing unit. The peptide
      solution or water was delivered to the sample compartments of the first unit. The
      solutions drained from the first unit were successively delivered to the second
      and third units. To the electrodes of three units, a direct electric current was
      applied. By using the present apparatus, peptides in casein hydrolysate can be
      continuously fractionated at least for 5 h. Better resolution was obtained in the
      second and third units.

PMID- 16448164
TI  - Novel approach to the detection and quantification of phenolic compounds in olive
      oil based on 31P nuclear magnetic resonance spectroscopy.
AB  - 31P NMR spectroscopy has been employed to detect and quantify phenolic compounds
      in the polar fraction of virgin olive oil. This novel analytical method is based
      on the derivatization of the hydroxyl and carboxyl groups of phenolic compounds
      with 2-chloro-4,4,5,5-tetramethyldioxaphospholane and the identification of the
      phosphitylated compounds on the basis of the 31P chemical shifts. Quantification
      of a large number of phenolic compounds in virgin olive oil can be accomplished
      by integration of the appropriate signals in the 31P NMR spectrum and the use of
      the phosphitylated cyclohexanol as internal standard. Finally, the validity of
      this technique for quantitative measurements was thoroughly examined.

PMID- 16448165
TI  - Influence of ingredients on the self-diffusion of aroma compounds in a model
      fruit preparation: an nuclear magnetic resonance-diffusion-ordered spectroscopy
      investigation.
AB  - Diffusion-ordered spectroscopy (DOSY)-pulsed field gradient (PGF) nuclear
      magnetic resonance (NMR) spectroscopy was used to measure self-diffusion
      coefficients of aroma molecules in model fruit preparations. The impact of the
      sucrose content on aroma diffusion was specifically investigated, and the
      relationship with viscosity, water activity, and dry matter parameters was
      evidenced. DOSY-PGF NMR spectroscopy was found to be a relevant and accurate
      technique to follow self-diffusion of aroma compounds at low concentrations in a
      complex food matrix and to obtain information on diffusion of the sucrose and of
      the water molecules. We showed that aroma self-diffusion was strongly decreased
      in fruit preparation because of the high sucrose content, which induces the
      formation of a network through hydrogen bonds with water. Self-diffusion
      coefficients were determined for aroma molecules of different natures, and values
      are related to the physicochemical properties of the molecule.

PMID- 16448166
TI  - Monitoring of moisture redistribution in multicomponent food systems by use of
      magnetic resonance imaging.
AB  - Differences in water activity within multicomponent food systems inevitably lead
      to moisture (re)distribution phenomena, hence deteriorating textural quality
      during shelf life. Noninvasive assessment of moisture transport in such systems
      would promote mechanistic understanding and enable rational development of
      strategies to control migration. Magnetic resonance imaging (MRI) is an ideal
      candidate for such a measurement technique, but its use in systems with low
      moisture components (e.g., cereal materials) is seriously hampered because of
      reduced transverse relaxation times. In this work, we report two MRI protocols
      for the noninvasive and quantitative assessment of moisture transport in
      multicomponent food products. The first protocol is suitable to study relatively
      slow (days/weeks) processes, whereas the second one is designed to study fast
      (hours) moisture transport. We have successfully applied this methodology to
      quantify moisture transport within multicomponent food systems, with adequate
      temporal and spatial resolution.

PMID- 16448167
TI  - Validated method for quantification of genetically modified organisms in samples
      of maize flour.
AB  - Sensitive and accurate testing for trace amounts of biotechnology-derived DNA
      from plant material is the prerequisite for detection of 1% or 0.5% genetically
      modified ingredients in food products or raw materials thereof. Compared to ELISA
      detection of expressed proteins, real-time PCR (RT-PCR) amplification has easier
      sample preparation and detection limits are lower. Of the different methods of
      DNA preparation CTAB method with high flexibility in starting material and
      generation of sufficient DNA with relevant quality was chosen. Previous RT-PCR
      data generated with the SYBR green detection method showed that the method is
      highly sensitive to sample matrices and genomic DNA content influencing the
      interpretation of results. Therefore, this paper describes a real-time DNA
      quantification based on the TaqMan probe method, indicating high accuracy and
      sensitivity with detection limits of lower than 18 copies per sample applicable
      and comparable to highly purified plasmid standards as well as complex matrices
      of genomic DNA samples. The results were evaluated with ValiData for homology of
      variance, linearity, accuracy of the standard curve, and standard deviation.

PMID- 16448168
TI  - Novel reference gene, PKABA1, used in a duplex real-time polymerase chain
      reaction for detection and quantitation of wheat- and barley-derived DNA.
AB  - We report the development of a duplex real-time Polymerase Chain Reaction (PCR)
      for the simultaneous detection and quantification of wheat- and barley-derived
      DNA. We used a single primer pair to amplify the single-copy gene PKABA1 from
      wheat and barley, using minor-groove-binding probes to distinguish between the
      two cereals. The assay was fully specific, and different wheat and barley
      cultivars exhibited similar Ct values, indicating stability across cultivars with
      respect to allelic and copy number composition. The limits of detection were 5
      and 10 PCR-forming units for wheat and barley, respectively, making the duplex
      assay as sensitive as other singleplex reference gene systems published. We were
      able to detect both wheat and barley simultaneously in real food samples, and the
      duplex assay is considered to be suitable as an endogenous reference gene system
      for the detection and quantification of wheat and barley in genetically modified
      organisms (GMO) and other food and feed analyses.

PMID- 16448169
TI  - Development and comparison of three diagnostic immunoassay formats for the
      detection of azoxystrobin.
AB  - The currently accepted method of detection for azoxystrobin, a strobilurin
      fungicide, involves a labor-intensive organic solvent extraction and gas
      chromatography analysis. Three diagnostic assay formats, i.e., enzyme-linked
      immunosorbent assay (ELISA), fluorescence polarization (FP), and time-resolved
      fluorescence (TR-FIA), were developed and compared with regard to detection and
      quantification of azoxystrobin in grape extract and river, lake, and well water
      samples. These three assay formats require no initial sample extraction and were
      not affected by any of the environmental matrices tested, and each had a linear
      working range of 0-400 pg/mL. The polyclonal antibodies used for each of the
      immunoassays were specific to azoxystrobin; that is, the highest cross-reactivity
      to other pesticides observed was 5.7%. The limits of detection of the
      immunoassays were similar at 3 (ELISA), 46 (FP), and 28 (TR-FIA) pg/mL, as were
      the respective IC50 values of 306, 252, and 244 pg/mL. Each of the three
      immunoassays developed was less labor-intensive and approximately 100-fold more
      sensitive than the gas chromatographic method. While the three formats were
      comparable in terms of performance, the fluorescence polarization assay was the
      least labor-intensive and required the least time to perform.

PMID- 16448170
TI  - Evaluation of chiral alpha-cyanoesters as general fluorescent substrates for
      screening enantioselective esterases.
AB  - Esterases play a crucial role in industrial chemical synthesis, maintaining
      normal physiological metabolism and detoxifying exogenous ester-containing
      toxicants. To meet the rapidly increasing industrial need for all kinds of
      esterases, especially enantioselective esterases used to generate highly pure
      chiral compounds, general substrates are necessary for rapid screening,
      monitoring, purification, and characterization. In this study, general
      fluorescent substrates including phenolic derivatives and alpha-cyanoesters were
      evaluated for sensitivity in detecting esterases in buffer systems. Results with
      two different esterases and different incubation times suggested that the alpha
      cyanoesters examined were significantly more sensitive at detecting esterases
      than the corresponding tested phenolic derivatives. More importantly, alpha
      cyanoesters, containing a secondary alcohol, possess at least one chiral center;
      thus, they are tools to screen for enantioselective hydrolysis. Results indicated
      that the enantioselectivity of esterases toward general alpha-cyanoesters
      strongly depended on the esterase and the substrate, but the majority of
      esterases examined preferred S-isomers to their corresponding R-enantiomers. Most
      appealing was the very high enantioselectivity displayed in cytosolic esterases
      of the house fly. The potential utility of such esterases is discussed. In
      addition, the use of alpha-cyanoesters as chiral fluorescent substrates was
      demonstrated for monitoring in enantioselective esterases.

PMID- 16448171
TI  - Composition of beer by 1H NMR spectroscopy: effects of brewing site and date of
      production.
AB  - A principal component analysis (PCA) of 1H NMR spectra of beers differing in
      production site (A, B, C) and date is described, to obtain information about
      composition variability. First, lactic and pyruvic acids contents were found to
      vary significantly between production sites, good reproducibility between dates
      being found for site A but not for sites B and C beers. Second, site B beers were
      clearly distinguished by the predominance of linear dextrins, while A and C beers
      were richer in branched dextrins. Carbohydrate reproducibility between dates is
      poorer for site C with dextrin branching degree varying significantly. Finally,
      all production sites were successfully distinguished by their contents in
      adenosine/inosine, uridine, tyrosine/tyrosol, and 2-phenylethanol,
      reproducibility between dates being again poorer for site C. Interpretation of
      the above compositional differences is discussed in terms of the biochemistry
      taking place during brewing, and possible applications of the method in brewing
      process control are envisaged.

PMID- 16448173
TI  - Direct aqueous injection liquid chromatography/electrospray ionization-mass
      spectrometry/mass spectrometry analysis of water for atrazine, simazine, and
      their chlorotriazine metabolites.
AB  - A method is reported for the determination of atrazine, simazine, and their
      respective dealkylated chlorotriazine metabolites in ground, surface, and
      finished drinking water. Water samples are diluted 1:4 in an injection vial prior
      to analysis using liquid chromatography/electrospray ionization-mass
      spectrometry/mass spectrometry (LC/ESI-MS/MS). The lower limit of method
      validation is 0.10 microg/L (ppb) for 2-chloro-4-(ethylamino)-6-isopropylamino)-s
      triazine (atrazine, G-30027), 2-chloro-4, 6-(diethylamino)-s-triazine (simazine,
      G-27692), 2-amino-4-chloro-6-(isopropylamino)-s-triazine (deethylatrazine, DEA,
      or G-30033), 2-amino-4-chloro-6-(ethylamino)-s-triazine (deisopropylatrazine,
      DIA, or G-28279), and 2,4-diamino-6-chloro-s-triazine (didealkylatrazine, DDA, or
      G-28273). The overall mean procedural recoveries (and % relative standard
      deviations) for atrazine, simazine, DEA, DIA, and DDA are 98 (4.4), 102 (3.6), 99
      (4.8), 103 (4.0), and 109% (4.8%), respectively, in finished drinking water; 108
      (2.7), 104 (5.4), 113 (4.5), 111 (5.2), and 105% (5.3%), respectively, in
      groundwater; and 96 (6.9), 103 (4.2), 102 (4.4), 102 (5.2), and 102% (8.2%),
      respectively, in surface water. The method validation was conducted under U.S.
      EPA FIFRA Good Laboratory Practice Guidelines 40 CFR 160.

PMID- 16448172
TI  - Sensitivity and specificity improvement of an ion sensitive field effect
      transistors-based biosensor for potato glycoalkaloids detection.
AB  - Butyryl cholinesterase of different origin along with variations of the time of
      enzyme immobilization on the potentiometric transducer surface is offered to
      control the ion sensitive field effect transistor (ISFET)-based biosensor
      sensitivity. Because butyryl cholinesterase has been already used to develop the
      sensors for heavy metals, organophosphorus/carbamate pesticides, and steroidal
      glycoalkaloids analysis, the present study has been focused on the investigation
      and adjustment of the ISFET-based biosensor specificity exclusively to the
      glycoalkaloids. Utilization of ethylendiaminetetracetate (a complexon of heavy
      metal ions) and phosphotriesterase (a highly efficient catalyst for the
      hydrolysis of organophosphorus compounds) enabled the highly specific
      determination of glycoalkaloids at the background of lead and mercury (up to 500
      microM of ions concentration) and paraoxon (up to 100 microM of pesticide
      concentration). The developed biosensor has been validated for glycoalkaloids
      detection in potato varieties cultivated in Ukraine, and the results obtained are
      compared to those measured by the methods of HPLC and TLC.

PMID- 16448174
TI  - Herbicidal and Fungicidal Activities of Lactones in Kava (Piper methysticum).
AB  - This is the first report showing that kava lactones are plant and plant fungus
      growth inhibitors. Aqueous extract of kava roots showed high allelopathic
      potential and strongly suppressed germination and growth of lettuce, radish,
      barnyardgrass, and monochoria. Nine kava lactones were detected using GC-MS
      including desmethoxyyagonin, kavain, 7,8-dihydrokavain, hydroxykavain, yagonin,
      5,6,7,8-tetrahydroxyyagonin, methysticin, dihydromethysticin, and 11-hydroxy-12
      methoxydihydrokavain. Quantities of desmethoxyyagonin, kavain, 7,8-dihydrokavain,
      yagonin, methysticin, and dihydromethysticin detected were 4.3, 6.9, 18.6, 5.7,
      1.4, and 5.4 mg/g of dry weight, respectively. These six major lactones in kava
      roots showed great herbicidal and antifungal activities. Growth of lettuce and
      barnyardgrass were significantly inhibited at 1-10 ppm, and four plant fungi
      including Colletotrichum gloeosporides, Fusarium solani, Fusarium oxysporum, and
      Trichoderma viride were significantly inhibited at 10-50 ppm. The biological
      activities of kava lactones were characterized by different double-bond linkage
      patterns in positions 5,6 and 7,8. The findings of this study suggest that kava
      lactones may be useful for the development of bioactive herbicides and
      fungicides.

PMID- 16448175
TI  - Effect of simulated gastrointestinal digestion on the antihypertensive properties
      of ACE-inhibitory peptides derived from ovalbumin.
AB  - Food-derived bioactive peptides with ACE-inhibitory properties are receiving
      special attention due to their beneficial effects in the treatment of
      hypertension. In this work we evaluate the impact of a simulated gastrointestinal
      digestion on the stability and activity of two bioactive peptides that derive
      from ovalbumin by enzymatic hydrolysis, YAEERYPIL and RADHPFL. These peptides
      possess in vitro ACE-inhibitory activity and antihypertensive activity in
      spontaneously hypertensive rats (SHR). The results showed that YAEERYPIL and
      RADHPFL were susceptible to proteolytic degradation after incubation with pepsin
      and a pancreatic extract. In addition, their ACE-inhibitory activity in vitro
      decreased after the simulated digestion. The antihypertensive activity on SHR of
      the end products of the gastrointestinal hydrolysis, YAEER, YPI, and RADHP, was
      evaluated. The fragments YPI and RADHP significantly decreased blood pressure, 2
      h after administration, at doses of 2 mg/kg, but they probably did not exert
      their antihypertensive effect through an ACE-inhibitory mechanism. It is likely
      that RADHP is also the active end product of the gastrointestinal digestion of
      the antihypertensive peptides FRADHPFL (ovokinin) and RADHPF (ovokinin 2-7).

PMID- 16448176
TI  - Structural requirements of Angiotensin I-converting enzyme inhibitory peptides:
      quantitative structure-activity relationship study of di- and tripeptides.
AB  - A database consisting of 168 dipeptides and 140 tripeptides was constructed from
      published literature to study the quantitative structure--activity relationships
      of angiotensin I-converting enzyme (ACE) inhibitory peptides. Two models were
      computed using partial least squares regression based on the three z-scores of 20
      coded amino acids and further validated by cross-validation and permutation
      tests. The two-component model could explain 73.2% of the Y-variance (inhibitor
      concentration that reduced enzyme activity by 50%, IC50) with the predictive
      ability of 71.1% for dipeptides, while the single-component model could explain
      47.1% of the Y-variance with the predictive ability of 43.3% for tripeptides.
      Amino acid residues with bulky side chains as well as hydrophobic side chains
      were preferred for dipeptides. For tripeptides, the most favorable residues for
      the carboxyl terminus were aromatic amino acids, while positively charged amino
      acids were preferred for the middle position, and hydrophobic amino acids were
      preferred for the amino terminus. According to the models, the IC50 values of
      seven new peptides with matchable primary sequences within pea protein, bovine
      milk protein, and soybean were predicted. The predicted peptides were
      synthesized, and their IC50 values were validated through laboratory
      determination of inhibition of ACE activity.

PMID- 16448177
TI  - Comparison of effects of high-pressure processing and heat treatment on
      immunoactivity of bovine milk immunoglobulin G in enriched soymilk under
      equivalent microbial inactivation levels.
AB  - Immunoglobulin-rich foods may provide health benefits to consumers. To extend the
      refrigerated shelf life of functional foods enriched with bovine immunoglobulin G
      (IgG), nonthermal alternatives such as high-pressure processing (HPP) may offer
      advantages to thermal processing for microbial reduction. To evaluate the effects
      of HPP on the immunoactivity of bovine IgG, a soymilk product enriched with milk
      protein concentrates, derived from dairy cows that were hyperimmunized with 26
      human pathogens, was subjected to HPP or heat treatment. To achieve a 5 log
      reduction in inoculated Escherichia coli 8739, the HPP or heat treatment
      requirements were 345 MPa for 4 min at 30 degrees C or for 20 s at 70 degrees C,
      respectively. To achieve a 5 log reduction in natural flora in the enriched
      soymilk, the HPP or heat treatments needed were 552 MPa for 4 min at 30 degrees C
      or for 120 s at 78.2 degrees C, respectively. At equivalent levels for a 5 log
      reduction in E. coli, HPP and heat treatment caused 25% and no detectable loss in
      bovine IgG activity, respectively. However, at equivalent levels for a 5 log
      reduction in natural flora, HPP and heat resulted in 65 and 85% loss of bovine
      IgG activity, respectively. Results of combined pressure-thermal kinetic studies
      of bovine milk IgG activity were provided to determine the optimal process
      conditions to preserve product function.

PMID- 16448178
TI  - Biosynthesis of 14C-phytoene from tomato cell suspension cultures (Lycopersicon
      esculentum) for utilization in prostate cancer cell culture studies.
AB  - This work describes the development and utilization of a plant cell culture
      production approach to biosynthesize and radiolabel phytoene and phytofluene for
      prostate cancer cell culture studies. The herbicide norflurazon was added to
      established cell suspension cultures of tomato (Lycopersicon esculentum cv. VFNT
      cherry), to induce the biosynthesis and accumulation of the lycopene precursors,
      phytoene and phytofluene, in their natural isomeric forms (15-cis-phytoene and
      two cis-phytofluene isomers). Norflurazon concentrations, solvent carrier type
      and concentration, and duration of culture exposure to norflurazon were screened
      to optimize phytoene and phytofluene synthesis. Maximum yields of both phytoene
      and phytofluene were achieved after 7 days of treatment with 0.03 mg
      norflurazon/40 mL fresh medium, provided in 0.07% solvent carrier. Introduction
      of 14C-sucrose to the tomato cell culture medium enabled the production of 14C
      labeled phytoene for subsequent prostate tumor cell uptake studies. In DU 145
      prostate tumor cells, it was determined that 15-cis-phytoene and an oxidized
      product of phytoene were taken up and partially metabolized by the cells. The
      ability to biosynthesize, radiolabel, and isolate these carotenoids from tomato
      cell cultures is a novel, valuable methodology for further in vitro and in vivo
      investigations into the roles of phytoene and phytofluene in cancer
      chemoprevention.

PMID- 16448179
TI  - Metabolism of curcuminoids in tissue slices and subcellular fractions from rat
      liver.
AB  - Curcumin and its natural congeners are of current interest because of their
      putative anti-inflammatory and anticarcinogenic activities, but knowledge about
      their metabolic fate is scant. In the present study conducted with precision-cut
      liver slices from male and female Sprague-Dawley rats, five reductive but no
      oxidative metabolites of curcumin and its demethoxy and bis-demethoxy analogues
      were observed and identified by HPLC and GC-MS analysis, mostly by comparison
      with authentic reference compounds. The major reductive metabolites were the
      hexahydrocurcuminoids in both male and female rat liver slices, whereas male rats
      formed more octahydro than tetrahydro metabolites and female rats more tetrahydro
      than octahydrocurcuminoids. Tetrahydro, hexahydro, and octahydro metabolites
      were predominantly present as glucuronides, but a significant proportion of
      sulfate conjugates was also observed. The lack of formation of oxidative
      metabolites of curcumin and the ready generation of reductive metabolites were
      confirmed using rat liver microsomes and cytosol, respectively. Results of
      enzymatic hydrolysis studies conducted under various conditions revealed that
      curcumin and demethoxycurcumin are chemically less stable than bis
      demethoxycurcumin, whereas the reductive metabolites of all three curcuminoids
      are stable compounds. This is the first report on the metabolism of
      demethoxycurcumin and bis-demethoxycurcumin. In view of the chemical instability
      of the parent curcuminoids, it is proposed to use their major phase I
      metabolites, that is, the stable hexahydro products, as biomarkers for exposure
      in clinical studies.

PMID- 16448180
TI  - Antioxidant and antiulcerative properties of phenolics from Chinese quince,
      quince, and apple fruits.
AB  - To evaluate the health benefits of Chinese quince and quince phenolics, their
      antioxidant properties and antiulcerative activity were investigated in
      comparison with apple phenolics as a reference. The strength of antioxidant
      activity and DPPH radical scavenging activity of these fruit phenolics varied
      according to different in vitro evaluation systems, whereas the antioxidative
      property of rat blood increased in all rats orally administered phenolics.
      Ferulic acid and isoferulic acid were detected as major metabolites in rats given
      apple phenolics, quince phenolics, and 5-caffeoylquinic acid standard. (-)
      Epicatechin and its 3'-O-methyl ether could be detected in rats administered
      apple phenolics and (-)-epicatechin standard. In the ethanol-induced gastric
      ulcer, pre-administration of Chinese quince and quince phenolics suppressed the
      occurrence of gastric lesions in rats, whereas apple phenolics seemed to promote
      ulceration. The trend of myeloperoxidase activity was similar to that of the
      ulcer index. The results showed that Chinese quince and quince phenolics might
      have health benefits by acting both in blood vessels and on the gastrointestinal
      tract.

PMID- 16448181
TI  - Antioxidative stress activity of oligophosphopeptides derived from hen egg yolk
      phosvitin in Caco-2 cells.
AB  - The protective effects of hen egg yolk phosvitin phosphopeptides (PPPs) against
      hydrogen peroxide (H2O2)-induced oxidative stress were evaluated in an in vitro
      assay using human intestinal epithelial cells. Caco-2 cells were stimulated with
      1 mM H2O2 for 6 h, and the secretion of IL-8, a proinflammatory mediator, was
      determined by ELISA as a biomarker of oxidative stress. The inhibition of H2O2
      induced IL-8 secretion from Caco-2 cells was observed by pretreatment for 2 h
      with PPPs, but not with phosvitin. PPPs also suppressed the formation of
      malondialdehyde in H2O2-treated Caco-2 cells. Furthermore, intracellular
      glutathione levels and glutathione reductase activity were elevated by the
      addition of PPPs. The protective effects of PPPs against H2O2-induced oxidative
      stress were almost the same as that of glutathione, and PPPs with a high content
      of phosphorus exhibited higher protective activity than PPPs without phosphorus;
      however, phosphoserine itself did not show any significant antioxidative stress
      activity. These findings suggest that oligophosphopeptides from hen egg yolk
      phosvitin possess novel antioxidative activity against oxidative stress in
      intestinal epithelial cells and that phosphorus and peptide structure seem to
      have a key role in the activity.

PMID- 16448182
TI  - Antioxidant activity and bioactive compounds of tea seed (Camellia oleifera
      Abel.) oil.
AB  - The oil of tea seed (Camellia oleifera Abel.) is used extensively in China as
      cooking oil. The objectives of this study were to investigate the antioxidant
      activity of tea seed oil and its active compounds. Of the five solvent extracts,
      methanol extract of tea seed oil exhibited the highest yield and the strongest
      antioxidant activity as determined by DPPH scavenging activity and Trolox
      equivalent antioxidant capacity (TEAC). Two peaks separated from the methanol
      extract by HPLC contributed the most significant antioxidant activity. These two
      peaks were further identified as sesamin and a novel compound: 2,5-bis
      benzo[1,3]dioxol-5-yl-tetrahydro-furo [3,4-d][1,3]dioxine (named compound B) by
      UV absorption and characterized by MS, IR, 1H NMR, and 13C NMR techniques.
      Sesamin and compound B decreased H2O2-mediated formation of reactive oxygen
      species in red blood cells (RBCs), inhibited RBCs hemolysis induced by AAPH, and
      increased the lag time of conjugated dienes formation in human low-density
      lipoprotein. The results indicate that both compounds isolated from tea seed oil
      exhibit remarkable antioxidant activity. Apart from the traditional
      pharmacological effects of Camellia oleifera, the oil of tea seed may also act as
      a prophylactic agent to prevent free radical related diseases.

PMID- 16448184
TI  - Novel antioxidant compounds from the aqueous extract of the roots of Decalepis
      hamiltonii (Wight and Arn.) and their inhibitory effect on low-density
      lipoprotein oxidation.
AB  - Roots of Decalepis hamiltonii are consumed as pickles and as a health drink in
      southern India for their health benefits. The antioxidant properties of the root
      extracts have been shown previously; this paper reports the isolation of
      antioxidant compounds from the aqueous extract of the roots of D. hamiltonii.
      Five novel antioxidant compounds were isolated and characterized by NMR and MS.
      The compounds exhibited free radical scavenging activity in vitro and inhibited
      low-density lipoprotein oxidation. This study demonstrates that the root extract
      of D. hamiltonii is a cocktail of several antioxidant compounds with health
      implications.

PMID- 16448183
TI  - Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its
      Metabolite Steviol on THP-1 Cells.
AB  - Stevioside, a natural noncaloric sweetener isolated from Stevia rebaudiana
      Bertoni, possesses anti-inflammatory and antitumor promoting properties; however,
      no information is available to explain its activity. The aim of this study was to
      elucidate the anti-inflammatory and immunomodulatory activities of stevioside and
      its metabolite, steviol. Stevioside at 1 mM significantly suppressed
      lipopolysaccharide (LPS)-induced release of TNF-alpha and IL-1beta and slightly
      suppressed nitric oxide release in THP-1 cells without exerting any direct toxic
      effect, whereas steviol at 100 microM did not. Activation of IKKbeta and
      transcription factor NF-kappaB were suppressed by stevioside, as demonstrated by
      Western blotting. Furthermore, only stevioside induced TNF-alpha, IL-1beta, and
      nitric oxide release in unstimulated THP-1 cells. Release of TNF-alpha could be
      partially neutralized by anti-TLR4 antibody. This study suggested that stevioside
      attenuates synthesis of inflammatory mediators in LPS-stimulated THP-1 cells by
      interfering with the IKKbeta and NF-kappaB signaling pathway, and stevioside
      induced TNF-alpha secretion is partially mediated through TLR4.

PMID- 16448185
TI  - Phosphinothricin analogues as inhibitors of plant glutamine synthetases.
AB  - A series of phosphinothricin derivatives with a modified methyl group, designed
      on the basis of the crystal structure of the complex formed by the inhibitor and
      the target enzyme from Salmonella typhimurium, were evaluated as potential
      inhibitors of plant glutamine synthetase. These compounds were previously shown
      to be equipotent or slightly weaker inhibitors to the lead compound against the
      bacterial enzyme. Because of the presence in higher plants of at least two enzyme
      forms with different subcellular localization and possible separate metabolic
      functions, plastidial and cytosolic glutamine synthetases were purified to
      electrophoretic homogeneity from spinach chloroplasts and cultured tobacco cells,
      respectively. Kinetic analysis confirmed the ability of the phosphinothricin
      analogues to inhibit both isoenzymes in the micromolar range, with a mechanism of
      a competitive type with respect to glutamate. Interestingly, some of them exerted
      a differential effect against either the two plant isoforms, or against the plant
      versus the bacterial enzyme.

PMID- 16448187
TI  - Antiproliferative terpenoids from almond hulls (Prunus dulcis): identification
      and structure-activity relationships.
AB  - Bioassay-guided fractionation of the EtOAc crude extract from Sicilian almond
      hulls, a waste material from Prunus dulcis crop, allowed identification of 10
      constituents, isolated as pure compounds (1-5, 7, and 10) or unseparable mixtures
      (5 + 6 and 8 + 9). All compounds were subjected to spectroscopic analysis and 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide bioassay on MCF-7
      human breast cancer cells. In addition to the main components oleanolic (1),
      ursolic (2), and betulinic (3) acids, the 2-hydroxy analogues alphitolic (4),
      corosolic (5), and maslinic (6) acids, as well as the related aldehydes, namely,
      betulinic (7), oleanolic (8), and ursolic (9), were identified. From a more polar
      fraction, the beta-sitosterol 3-O-glucoside (10) was also identified. A sample of
      commercially available betulin (11) was also included in bioassays as further
      support to a structure-activity relationship study. Betulinic acid showed
      antiproliferative activity toward MCF-7 cells (GI50 = 0.27 microM), higher than
      the anticancer drug 5-fluorouracil.

PMID- 16448186
TI  - Free-radical-scavenging and antioxidant activities of secondary metabolites from
      reddened cv. Annurca apple fruits.
AB  - Forty-three secondary metabolites were isolated and characterized from cv.
      Annurca apple fruit, an apple variety cultivated in the south of Italy. This
      apple cultivar undergoes a typical reddening treatment after collection. All of
      the compounds were characterized on the basis of their spectroscopic data. The
      compounds were tested for their radical-scavenging and antioxidant activities by
      measuring their capacity to scavenge DPPH* (2,2'-diphenyl-1-picrylhydrazyl
      radical), H2O2, and NO (nitric oxide) and to inhibit the formation of methyl
      linoleate conjugated diene hydroperoxides or TBARS (thiobarbituric acid reactive
      species).

PMID- 16448188
TI  - Codon optimization of Candida rugosa lip1 gene for improving expression in Pichia
      pastoris and biochemical characterization of the purified recombinant LIP1
      lipase.
AB  - An important industrial enzyme, Candida rugosa lipase (CRL) possesses several
      different isoforms encoded by the lip gene family (lip1-lip7), in which the
      recombinant LIP1 is the major form of the CRL multigene family. Previously, 19 of
      the nonuniversal serine codons (CTG) of the lip1 gene hav been successfully
      converted into universal serine codons (TCT) by overlap extension PCR-based
      multiple-site-directed mutagenesis to express an active recombinant LIP1 in the
      yeast Pichia pastoris. To improve the expression efficiency of recombinant LIP1
      in P. pastoris, a regional synthetic gene fragment of lip1 near the 5' end of a
      transcript has been constructed to match P. pastoris-preferred codon usage for
      simple scale-up fermentation. The present results show that the production level
      (152 mg/L) of coLIP1 (codon-optimized LIP1) has an overall improvement of 4.6
      fold relative to that (33 mg/L) of non-codon-optimized LIP1 with only half the
      cultivation time of P. pastoris. This finding demonstrates that the regional
      codon optimization the lip1 gene fragment at the 5' end can greatly increase the
      expression level of recombinant LIP1 in the P. pastoris system. More distinct
      biochemical properties of the purified recombinant LIP1 for further industrial
      applications are also determined and discussed in detail.

PMID- 16448189
TI  - Regiospecific flavonoid 7-O-methylation with Streptomyces avermitilis O
      methyltransferase expressed in Escherichia coli.
AB  - O-Methylation, commonly found in synthesis of secondary metabolites of plants and
      micro-organisms, appears to transfer a methyl group to the hydroxyl group of the
      recipient which increases the hydrophobicity of the recipient. O
      Methyltransferase (OMT), , was isolated and characterized from Streptomyces
      avermitilis MA-4680. Its amino acid sequence showed 68% similarity with
      antibiotic C-1027 OMT and 53% similarity with the carminomycin 4-OMT. was
      expressed in E. coli as a His-tag fusion protein and showed that the methyl was
      transferred onto the 7-hydroxyl group of the isoflavones, daidzein and genistein,
      and the flavones, kaempferol and quercetin, as well as the flavanone naringenin.
      NMR and liquid chromatography-mass spectrometry were used to confirm the location
      of the methyl group on the recipient compound of naringenin, which was
      biotransformed into sakuranetin by E. coli transformant expressing (E. coli Sa
      2). Therefore, E. coli Sa-2 would be used for the synthesis of the antifungal
      flavonoid, sakuranetin, through biotransformation.

PMID- 16448190
TI  - Purification and characterization of a chimeric Cry1F delta-endotoxin expressed
      in transgenic cotton plants.
AB  - Cotton plants were genetically modified through the introduction of a synthetic
      gene that encodes a Bacillus thuringiensis insecticidal protoxin referred to as
      Cry1F(synpro). This protoxin is a chimeric, full-length delta-endotoxin of 130
      kDa, comprised of the core toxin of Cry1Fa2 protein and parts of the nontoxic
      portions of Cry1Ca3 and Cry1Ab1 proteins, all of which originated from Bacillus
      thuringiensis. The Cry1F(synpro) expressed in cotton plants confers resistance to
      lepidopteran pests. The current study was conducted to characterize the
      Cry1F(synpro) protein expressed in the transgenic cotton event 281-24-236.
      Results showed that the full-length Cry1F(synpro) produced in the transgenic
      cotton plants was sensitive to the host cell protease cleavage, resulting in a
      truncated, biologically active form (core toxin) with an apparent molecular mass
      of 65 kDa. This truncated toxin was purified by immunoaffinity chromatography
      from the cotton leaf extract. N-terminal sequencing, peptide mass fingerprinting
      by MALDI-TOF MS, and internal peptide sequencing by MS/MS confirmed the identity
      of the truncated core toxin of Cry1F. The mechanism of truncation was explored
      with Cry1F(synpro) derived from a recombinant Pseudomonas fluorescens. The
      transgenic cotton-produced Cry1F showed equivalent insecticidal activity to that
      of Pseudomonas fluorescens-derived Cry1F.

PMID- 16448191
TI  - Molecular cloning, purification, and biochemical characterization of a novel
      pyrethroid-hydrolyzing esterase from Klebsiella sp. strain ZD112.
AB  - The gene encoding pyrethroid-hydrolyzing esterase (EstP) from Klebsiella sp.
      strain ZD112 was cloned into Escherichia coli and sequenced. A sequence analysis
      of the DNA responsible for the estP gene revealed an open reading frame of 1914
      bp encoding for a protein of 637 amino acid residues. No similarities were found
      by a database homology search using the nucleotide and deduced amino acid
      sequences of the esterases and lipases. EstP was heterologously expressed in E.
      coli and purified. The molecular mass of the native enzyme was approximately 73
      kDa as determined by gel filtration. The results of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and the deduced amino acid sequence of EstP
      indicated molecular masses of 73 and 73.5 kDa, respectively, suggesting that EstP
      is a monomer. The purified EstP not only degraded many pyrethroid pesticides and
      the organophosphorus insecticide malathion, but also hydrolyzed rho-nitrophenyl
      esters of various fatty acids, indicating that EstP is an esterase with broad
      substrates. The K(m) for trans- and cis-permethrin and k(cat)/K(m) values
      indicate that EstP hydrolyzes both these substrates with higher efficiency than
      the carboxylesterases from resistant insects and mammals. The catalytic activity
      of EstP was strongly inhibited by Hg2+, Ag+, and rho-chloromercuribenzoate,
      whereas a less pronounced effect (3-8% inhibition) was observed in the presence
      of divalent cations, the chelating agent EDTA, and phenanthroline.

PMID- 16448192
TI  - Identification of two novel pigment precursors and a reddish-purple pigment
      involved in the blue-green discoloration of onion and garlic.
AB  - By using a model reaction system representing blue-green discoloration that
      occurs when purees of onion (Allium cepa L.) and garlic (Allium sativum L.) are
      mixed, we isolated two pigment precursors (PPs) and a reddish-purple pigment (PUR
      1) and determined their chemical structures. PPs were isolated from a heat
      treated solution containing color developer (CD) and either l-valine or l
      alanine, and their structures were determined as 2-(3,4-dimethylpyrrolyl)-3
      methylbutanoic acid (PP-Val), and 2-(3,4-dimethyl-1H-pyrrolyl) propanoic acid (PP
      Ala), respectively. Next, PUR-1 was isolated from a heat-treated solution
      containing PP-Val and allicin, and its structure was determined as (1E)-1-(1
      ((1S)-1-carboxy-2-methylpropyl)-3,4-dimethyl-1H-pyrrol-2-yl)-prop-1-enylene-3-(1
      ((1S)-1-carboxy-2-methylpropyl)-3,4-dimethyl-1H-pyrrol-2-ylidenium). The
      structure of PUR-1 suggested that PP molecules containing a 3,4-dimethyl pyrrole
      ring had been cross-linked by an allyl group of allicin to form conjugated
      pigments. While PUR-1 is a dipyrrole compound exhibiting a reddish-purple color,
      a color shift toward blue to green can be expected as the cross-linking reaction
      continues to form, for example, tri- or tetrapyrrole compounds.

PMID- 16448193
TI  - Model studies on precursor system generating blue pigment in onion and garlic.
AB  - Reactions involved in blue-green discoloration in a mixture of onion (Allium cepa
      L.) and garlic (Allium sativum L.) were investigated. Vivid-blue color was
      successfully reproduced by using a defined model reaction system comprising only
      trans-(+)-S-(1-propenyl)-L-cysteine sulfoxide (1-PeCSO) from onion, S-allyl-L
      cysteine sulfoxide (2-PeCSO) from garlic, purified alliinase (EC 4.4.1.4), and
      glycine (or some other amino acids). Four reaction steps identified and factors
      affecting the blue color formation were in good agreement with those suggested by
      earlier investigators. When crude onion alliinase was used in place of garlic
      alliinase, less pigment was formed. This result was explained by a difference in
      the amount of thiosulfinates, colorless intermediates termed color developers,
      yielded from 1-PeCSO by these enzymes.

PMID- 16448194
TI  - Investigation of the correlation of the acrylamide content and the antioxidant
      activity of model cookies.
AB  - The purpose of this study was to evaluate the correlation between the acrylamide
      (AA) content and the antioxidant activity (AOA) of self-prepared cookies. Cookies
      were baked in the laboratory under defined conditions following four different
      recipes. The parameters of investigation were the influence of the type and
      relative content of sugar (glucose and fructose) and the baking time on the AA
      content as well as AOA of the final products. Parameters depending on the recipe
      and baking conditions such as the moisture content, the total nitrogen
      concentration, and the color of the products were evaluated for all samples as
      well. To prove the transferability of the findings gained with model cookies to
      samples from industry, the same measurements were performed on seven different
      types/brands of cookies that were purchased in local markets. A direct
      correlation was found between the concentration of AA and the AOA. With
      increasing baking time, the moisture content of the cookies decreased. The latter
      parameter correlated well with the AA concentration and AOA. The use of fructose
      enhanced the concentration of AA and the AOA of the final products, when compared
      with the use of sucrose. However, a simple model for the prediction of acrylamide
      contents and the AOA of samples from the baking time, color, protein, or moisture
      content of the samples was not found.

PMID- 16448195
TI  - Role of different factors affecting the formation of 5-hydroxymethyl-2
      furancarboxaldehyde in heated grape must.
AB  - The influence of concentration and water activity (a(w)) on the formation of 5
      hydroxymethyl-2-furancarboxaldehyde (HMF) in thermally treated grape must was
      evaluated. Must was cryoconcentrated and then heated to study the pure effect of
      sugar concentration. Moreover, NaCl was added to the must to lower a(w),
      maintaining the same sugar concentration, with the purpose of evaluating the pure
      effect of a(w). Finally, the influence of minimal pH changes on the formation of
      HMF was evaluated by means of a model solution. The results showed that a(w) and
      sugar concentration are both determinant in the formation of HMF in grape must.
      Sugar concentration influences the reaction by supplying substrates; low a(w)
      enhances the formation of HMF by changing the equilibrium in the dehydration step
      of the reaction.

PMID- 16448196
TI  - Influence of the distillation step on the ratios of stable isotopes of ethanol in
      cherry brandies.
AB  - Isotope ratio mass spectrometry and site-specific natural isotope fractionation
      nuclear magnetic resonance were applied to determine the overall carbon isotope
      ratio (delta13C) and the hydrogen isotope ratios [(D/H)I and (D/H)II] of ethanol,
      respectively. Ethanol was obtained by distillation of fermented cherry mash from
      a pot still commonly used in fruit brandy production. Analyses of distillate
      fractions revealed that the distillation proceeds with a fractionation of ethanol
      isotopologues. The inverse vapor pressure isotope effect (VPIE) observed for the
      carbon isotopologues is in accordance with the data reported for distillation of
      ethanol in spinning band columns. In contrast, the inverse VPIE for hydrogen
      isotopologues of ethanol observed in spinning band columns could not be
      confirmed. To investigate whether the observed isotope fractionations might
      influence the applicability of stable isotope analysis for quality and
      authenticity assessment of fruit brandies, the collected distillate fractions
      were recombined to cuts, as is common practice in commercial fruit brandy
      production. Taking into consideration the limits of repeatability of the method,
      it could be demonstrated that the isotope fractionations observed do not impair
      the applicability of stable isotope analysis of the carbon and hydrogen isotopes
      of ethanol for the authenticity assessment of cherry brandies if the cuts are
      placed in accordance with common distillers' practice.

PMID- 16448197
TI  - Postharvest variation in apple (Malus x domestica Borkh.) Flavonoids following
      harvest, storage, and 1-MCP treatment.
AB  - The impact of 1-methylcyclopropene (1-MCP) on the synthesis and retention of
      flavonoid compounds during storage and ripening of red Delicious (Malus x
      domestica Borkh.) apples was investigated. Numerous anthocyanins, flavonols,
      flavan-3-ols, and a hydroxycinnamic acid from three different fruit harvest
      maturities were monitored after a 120 day storage and 1 week shelf life period
      using high-performance liquid chromatography/diode array detector analysis. The
      total flavonoid concentration was 5% greater in fruit treated with 1-MCP, whereas
      chlorogenic acid levels were 24% lower. All compounds analyzed increased in
      concentration during fruit harvest; however, the anthocyanins generally declined
      after storage, while chlorogenic acid levels increased. 1-MCP treatment resulted
      in the retention of anthocyanins in the latter stages of storage but did not
      affect the flavonols and flavan-3-ols. Chlorogenic acid biosynthesis from early
      and optimal fruit harvest maturities was greatly inhibited by 1-MCP during
      storage and the 1 week shelf life period. However, 1-MCP did not affect
      chlorogenic acid concentrations in late-harvested fruit. Results suggest that 1
      MCP may inhibit the activity of phenylalanine ammonia-lyase and subsequent
      biosynthesis of flavonoid compounds. However, because very little postharvest
      biosynthesis of flavonoids occurs in apples, 1-MCP treatment may be useful for
      maintaining some of the intrinsic flavonoid levels of red Delicious apples, if
      applied at the proper harvest maturity.

PMID- 16448198
TI  - Fate of the Cry1Ab protein from Bt-maize MON810 silage in biogas production
      facilities.
AB  - Biogas plants fuelled with renewable sources of energy are a sustainable means
      for power generation. In areas with high infestation levels with the European
      corn borer, Ostrinia nubilalis (Hbn.), it is likely that transgenic Bt-maize will
      be fed into agricultural biogas plants. The fate of the entomotoxic protein
      Cry1Ab from MON810 maize was therefore investigated in silage and biogas
      production-related materials in the utilization chains of two farm-scale biogas
      plants. The Cry1Ab content in silage exhibited no clear-cut pattern of decrease
      over the experimental time of 4 months. Mean content for silage was 1878 +/- 713
      ng Cry1Ab g(-1). After fermentation in the biogas plants, the Cry1Ab content
      declined to trace amounts of around 3.5 ng g(-1) in the effluents. The limit of
      detection of the employed ELISA test corresponded to 0.75 ng Cry1Ab g(-1) sample
      material. Assays with larvae of O. nubilalis showed no bioactivity of the reactor
      effluents. The utilization of this residual material as fertilizer in agriculture
      is therefore deemed to be ecotoxicologically harmless.

PMID- 16448199
TI  - Apple procyanidin oligomers absorption in rats after oral administration:
      analysis of procyanidins in plasma using the porter method and high-performance
      liquid chromatography/tandem mass spectrometry.
AB  - In this study, we investigated the absorption of apple procyanidins, namely,
      apple condensed tannins (ACTs), in rats using the Porter method and high
      performance liquid chromatography/tandem mass spectrometry. The apple procyanidin
      concentrations in the rat plasma reached a maximum 2 h after administration and
      decreased thereafter. To investigate the limits of the absorption of apple
      procyanidins in the polymerization degree, we administered the procyanidin
      oligomer fraction, which was separated from ACT using normal-phase chromatography
      according to the degree of polymerization. Procyanidins from each dimer to
      pentamer group were detected in the plasma by the Porter method. Moreover, by the
      study using reconstituted procyanidins, polymeric procyanidins influenced the
      absorption of procyanidin oligomers. These results suggest that ACTs are absorbed
      and directly involved in physiological functions in the rats.

PMID- 16448200
TI  - An in vitro study on the postinfection activities of copper hydroxide and copper
      sulfate against conidia of Venturia inaequalis.
AB  - The postinfection activities of copper hydroxide [Cu(OH)2] and copper sulfate
      (CuSO4) against apple scab (Venturia inaequalis) were evaluated in an in vitro
      study. Our intention was to support the aim of reducing copper application rates
      by appropriate timing of applications. Experiments were conducted at 20 degrees C
      with leaf disks and isolated cuticular membranes (CM) of Malus x domestica
      'Gloster' and 'Elstar'. Conidia of V. inaequalis were used as the inoculum. In
      untreated controls, 7.9 and 33.2% of germinated conidia formed primary stromata
      24 and 48 h after inoculation, respectively. Treatments with copper compounds
      were applied 24 and 48 h after inoculation, which was 16 and 40 h after infection
      had occurred. When working with CM and using fluorescein diacetate as a vital
      stain, vital and dead stromata could be distinguished. Treatment effects were
      assessed 72 h after inoculation by counting vital (fluorescing) primary stromata.
      With leaf disks, the number of stromata was counted using KOH-aniline blue
      fluorescence staining. Cu(OH)2 and CuSO4 showed postinfection activity and killed
      primary stromata, provided that the surface of the CM was kept wet. Cu(OH)2 was
      more effective than CuSO4 and was able to kill all primary stromata 24 h after
      inoculation at concentrations of 116 and 231 mg L(-1). When Cu(OH)2 was applied
      at 116 mg L(-1) to leaf disks 24 h after inoculation, the number of primary
      stromata did not significantly differ from the control. Results indicate
      different modes of action for the highly water soluble CuSO4 and the slightly
      soluble Cu(OH)2. This supports the hypothesis that spore exudates react with
      insoluble copper compounds and form highly toxic copper complexes. Application of
      Cu(OH)2 to dry CM did not kill primary stromata. Hence, for Cu(OH)2 to exert
      postinfection activity, leaves must be wet. In the field, this cannot be
      guaranteed and a postinfection application of Cu(OH)2 cannot be recommended.

PMID- 16448201
TI  - Determination of fungicide residues in field-grown strawberries following
      different fungicide strategies against gray mold (Botrytis cinerea).
AB  - In a 2 year experiment, residues in field-grown strawberries were investigated
      from the fungicides fenhexamid, pyrimethanil, tolylfluanid, and kresoxim-methyl
      resulting from different strategies, as regards the dose, number, and time of
      fungicide applications. Kresoxim-methyl was only used the first year and in full
      or no dose to control powdery mildew. In the first year, the highest
      concentrations analyzed were 0.66 mg kg(-1) for pyrimethanil and 0.63 mg kg(-1)
      for fenhexamid resulting from the use of recommended dose rates and a preharvest
      interval (PHI) of 10 days, thus not exceeding the Danish maximum residue limit
      (MRL) of 1 mg kg(-1). Tolylfluanid was used no later than 21 days before harvest,
      which left residue contents in the berries of 0.48 mg kg(-1), a value well below
      the MRL of 5 mg kg(-1). In the second year, fungicide residues found in the
      samples were generally lower, 0.39 and 0.03 mg kg(-1) for pyrimethanil and
      fenhexamid, respectively. No residues of kresoxim-methyl were found in any of the
      samples from the field trials, indicating that kresoxim-methyl residues had
      declined to a level well below the detection limit within the 28 day period
      between the last application and the harvest.

PMID- 16448202
TI  - Sensory and chemical characterization of the aroma of a white wine made with
      Devin grapes.
AB  - The aroma profile of a Slovak white wine made with Devin grapes was evaluated by
      13 expert judges. The panel evaluated the orthonasal and retronasal aroma
      profiles, as well as the profile of residual wine aroma found in the empty glass
      after the consumption. For the majority of attributes, the orthonasal perception
      was the most intense, followed by retronasal, and finally by the residual odor.
      Varietal wine Devin possessed primarily a "Muscat" odor by nose, together with
      intense fruity, sweet, and herbaceous notes. Data were analyzed by generalized
      procrustes analysis. Two primary clusters separated orthonasal ratings from both
      retronasal and residual odor ratings. Similar results were obtained by analysis
      of variance. The relative proportion of "heavy" aroma notes, likely related to
      polar odorants, increased in retronasal and residual odor profiles. The gas
      chromatography-olfactometry profile revealed a great complexity and showed that
      the characteristic aroma of this variety seems to be a mixture of Muscat,
      Gewurztraminer, and Sauvignon-Blanc, being rich in linalool, cis-rose oxide, and
      4-methyl-4-mercaptopentanone.

PMID- 16448203
TI  - Characterization of the key aroma compounds in the beverage prepared from
      Darjeeling black tea: quantitative differences between tea leaves and infusion.
AB  - By application of the aroma extract dilution analysis on the volatile fraction
      isolated from a black tea infusion (Darjeeling Gold Selection), vanillin (vanilla
      like), 4-hydroxy-2,5-dimethyl-3(2H)-furanone (caramel), 2-phenylethanol
      (flowery), and (E,E,Z)-2,4,6-nonatrienal (oat-flake-like) were identified with
      the highest flavor dilution (FD) factors among the 24 odor-active compounds
      detected in the FD factor range of 4-128. Quantitative measurements performed by
      means of stable isotope dilution assays and a calculation of odor activity values
      (OAVs; ratio of concentration to odor threshold in water) revealed, in
      particular, the previously unknown tea constituent (E,E,Z)-2,4,6-nonatrienal as a
      key odorant in the infusion and confirmed the important role of linalool and
      geraniol for the tea aroma. An aroma recombinate performed by the 18 odorants for
      which OAVs > 1 were determined in their "natural" concentrations matched the
      overall aroma of the tea beverage. In the black tea leaves, a total of 42
      odorants were identified, most of which were identical with those in the beverage
      prepared thereof. However, quantitative measurements indicated that, in
      particular, geraniol, but also eight further odorants were significantly
      increased in the infusion as compared to their concentration in the leaves.

PMID- 16448204
TI  - Visualization of single and aggregated hulless oat (Avena nuda L.) (1-->3),(1-
      >4)-beta-D-glucan molecules by atomic force microscopy and confocal scanning
      laser microscopy.
AB  - Surfactants were used to disperse oat beta-glucan. Atomic force microscopy (AFM)
      images of the resulting samples revealed a distribution of extended chainlike
      molecules and allowed, for the first time, direct visualization of single oat
      beta-glucan molecules with cross-sectional heights of about 0.44 nm. The number
      average contour length (L(n)) and root-mean-square end-to-end distance
      ((R(ee)2)(1/2)) measured from the AFM images were 938 and 912 nm, respectively.
      The calculated persistence length (L(p)) was 526 nm. The weight-average molecular
      weight (M(w)) calculated from single beta-glucan molecules was 4.43 x 10(5).
      Samples without surfactant showed a strong tendency to form aggregates. The
      sample concentration, reserving time, and calcofluor as well as freezing could
      affect the formation of aggregates. These aggregates were visualized by both AFM
      and confocal scanning laser microscopy. The shape of the aggregates changed from
      small dots with diameters of approximately 20-50 nm to microfibrils over 3 microm
      long with the increasing of the concentration of oat beta-glucan from 10 to 100
      microg/mL. The particle size distribution obtained by a laser particle size
      analyzer was 926 nm, which confirmed the size of oat beta-glucan molecules
      obtained from AFM images.

PMID- 16448205
TI  - Flavonoids as mushroom tyrosinase inhibitors: a fluorescence quenching study.
AB  - Flavonoids, a group of naturally occurring antioxidants and metal chelators, can
      be used as tyrosinase inhibitors due to their formation of copper-flavonoid
      complexes. Thus, to investigate the underlying inhibition mechanism, a large
      group of flavonoids from several major flavones and flavonols were tested using
      fluorescence quenching spectroscopy. In addition, large differences in the
      tyrosinase inhibitory activities and chelating capacities according to the
      location of the hydroxyl group(s) in combination with the A and B rings in the
      flavonoids were confirmed. Accordingly, the major conclusions from this work are
      as follows: (i) The tyrosinase inhibitory activity is not only dependent on the
      number of hydroxyl groups in the flavonoids, (ii) the enzyme is primarily
      quenched by the hydroxyl group(s) of A and B rings on the ether side of the
      flavonoids, and (iii) the tyrosinase inhibitory activity of 7,8,3',4'
      tetrahydroxyflavone is supported by a virtual model of docking with the mushroom
      tyrosinase, which depicts the quenching of the enzyme. The results also
      demonstrated that the dihydroxy substitutions in the A and B rings are crucial
      for Cu2+-chelate formation, thereby influencing the tyrosinase inhibitory
      activity.

PMID- 16448206
TI  - Action mechanism of an angiotensin I-converting enzyme inhibitory peptide derived
      from chicken breast muscle.
AB  - In a previous study, we isolated the inhibitory peptide (P4 peptide, Gly-Phe-Hyp
      Gly-Thr-Hyp-Gly-Leu-Hyp-Gly-Phe) for angiotensin I-converting enzyme (ACE) from
      chicken breast muscle extract possessing hypotensive activity for spontaneously
      hypertensive rats (SHRs). This study was performed to elucidate the peptide's
      action mechanisms of inhibiting ACE. Intravenous administration of synthetic P4
      peptide resulted in significant drops in the blood pressures of SHRs. As Dixon
      plots indicate, the P4 peptide showed high affinity toward ACE (K(i) = 11.48
      microM) and only 10% of the total amount of the P4 peptide was decomposed. The
      analyses of the relationship between the ACE inhibitory activity and structure of
      the P4 peptide clarified that Hyp-Gly-Leu-Hyp-Gly-Phe showed a stronger activity
      (IC50 = 10 microM) than the P4 peptide (IC50 = 46 microM). When Phe at the C
      terminus of the P4 peptide was deleted, IC50 changed to 25000 microM, indicating
      that Phe at the C-terminus of the peptide is very important for ACE inhibitory
      activity.

PMID- 16448208
TI  - Development of yellow pigmentation in squid (Loligo peali) as a result of lipid
      oxidation.
AB  - The impact of lipid oxidation on yellow pigment formation in squid lipids and
      proteins was studied. When the squid microsomes were oxidized with iron and
      ascorbate, thiobarbituric acid reactive substance were observed to increase
      simultaneously with b values (yellowness) and pyrrole compounds concomitantly
      with a decrease in free amines. Oxidized microsomes were not able to change the
      solubility, sulfhydryl content, or color of salt-soluble squid myofibrillar
      proteins. Aldehydic lipid oxidation products were able to decrease solubility and
      sulfhydryl content of salt-soluble squid myofibrillar proteins but had no impact
      on color. Aldehydic lipid oxidation products increased b values (yellowness) and
      pyrrole compounds and decreased free amines in both squid phospholipid and egg
      yolk lecithin liposomes. The ability of aldehydic lipid oxidation products to
      change the physical and chemical properties of egg yolk lecithin liposomes
      increased with increasing level of unsaturation and when the carbon number was
      increased from 6 to 7. These data suggest that off-color formation in squid
      muscle could be due to nonenzymatic browning reactions occurring between
      aldehydic lipid oxidation products and the amines on phospholipids headgroups.

PMID- 16448207
TI  - Dual positional and stereospecificity of lipoxygenase isoenzymes from germinating
      barley (green malt): biotransformation of free and esterified linoleic acid.
AB  - The lipoxygenase isoenzymes LOX1 and LOX2 from green malt were separated by
      isoelectric focusing, and their catalytic properties regarding complex lipids as
      substrates were characterized. The regio- and stereoisomers of hydroperoxy
      octadecadienoates (HPODE) resulting from LOX1 and LOX2 enzymatic transformations
      of linoleic acid, methyl linoleate, linoleic acid glycerol esters monolinolein,
      dilinolein, and trilinolein, and 1-palmitoyl-2-linoleoyl-glycero-3-phosphocholine
      (PamLinGroPCho) were determined. In addition, biotransformations of polar and
      nonpolar lipids extracted from malt were performed with LOX1 and LOX2. The
      results show that LOX2 catalyzes the oxidation of esterified fatty acids at a
      higher rate and is more regioselective than LOX1. The dual position specificity
      of LOX2 (9-HPODE:13-HPODE) with trilinolein as the substrate (6:94) was higher
      than the resultant ratio (13:87) when free linoleic acid was transformed. A high
      (S)-enantiomeric excess of 13-HPODE was analyzed with all esterified substrates
      confirming the formation of 13-HPODE through the LOX2 enzyme; however, 9-HPODE
      detected after LOX2 biotransformations showed (R)-enantiomeric excesses.
      PamLinGroPCho was oxygenated by LOX1 with the highest regio- and
      stereoselectivities among the applied substrates.

PMID- 16448209
TI  - Microbially safe utilization of non-inactivated oats (Avena sativa L.) for
      production of conjugated linoleic acid.
AB  - A microbially safe process for the enrichment of conjugated linoleic acid (CLA)
      in oats was developed. The process consists of hydrolysis of oat lipids by non
      inactivated oat flour, followed by propionibacterium-catalyzed isomerization of
      the resulting free linoleic acid to CLA. The first stage was performed at water
      activity (a(w)) 0.7, where hydrolysis of triacylglycerols progressed efficiently
      without growth of the indigenous microflora of flour. Thereafter, the flour was
      incubated as a 5% (w/v) aqueous, sterilized slurry with Propionibacterium
      freudenreichii ssp. shermanii. The amount of CLA produced in 20 h was 11.5 mg/g
      dry matter corresponding to 116 mg/g lipids or 0.57 mg/mL slurry. The oat flour
      had also the capability to hydrolyze exogenous oils at a(w) 0.7. Sunflower oil,
      added to increase linoleic acid content in triacylglycerols 2.7-fold, was
      hydrolyzed rapidly. Isomerization of this oil-supplemented flour as a 5% slurry
      gave final CLA content of 22.3 mg/g dry matter after 50 h of fermentation,
      corresponding to 118 mg/g lipids or 1.14 mg/mL slurry. Storage stability of CLA
      in fermented oat slurries at 4 degrees C was good.

PMID- 16448210
TI  - Purification and characterization of trimethylamine-N-oxide demethylase from
      jumbo squid (Dosidicus gigas).
AB  - Trimethylamine-N-oxide demethylase (TMAOase) was purified from Jumbo squid
      (Dosidicus gigas) and characterized in detail herein. The TMAOase was extracted
      from squid with 20 mM Tris-acetate buffer (pH 7.0) containing 1.0 M NaCl,
      followed by acid treatment and heat treatment. Then it was purified by
      deithylaminoethyl-cellulose and Sephacryl S-300 chromatography, subsequently
      resulting in an 839-fold purification. The molecular mass of the TMAOase was
      defined to be 17.5 kDa. The optimum pH of the purified TMAOase was 7.0, and its
      optimum temperature was confirmed to be 55 degrees C. The TMAOase was stable to
      heat treatment up to 50 degrees C and stable at pH 7.0-9.0. Reducing agents such
      as DTT, Na2SO3, and NADH were effective at activating TMAOase, and
      ethylenediaminetetraacetic acid, as well as Mg2+ and Ca2+, could also enhance the
      activity of TMAOase remarkably, whereas the TMAOase could be significantly
      inhibited by tea polyphenol, phytic acid and acetic acid. In addition, the
      TMAOase converted TMAO to dimethylamine and formaldehyde stoichiometrically with
      a K(m) of 26.2 mM.

PMID- 16448211
TI  - Crocetin esters, picrocrocin and its related compounds present in Crocus sativus
      stigmas and Gardenia jasminoides fruits. Tentative identification of seven new
      compounds by LC-ESI-MS.
AB  - Crocetin esters present in saffron (Crocus sativus L.) stigmas and in Gardenia
      jasminoides Ellis fruit are the compounds responsible for their color. Of the
      fifteen crocetin esters identified in this study, five new compounds were
      tentatively identified: trans and cis isomers of crocetin (beta-D-triglucoside)
      (beta-D-gentibiosyl) ester, trans and cis isomers of crocetin (beta-D
      neapolitanose)-(beta-D-glucosyl) ester, and cis crocetin (beta-D-neapolitanose)
      (beta-D-gentibiosyl) ester. The most relevant differences between both species
      were a low content of the trans crocetin (beta-D-glucosyl)-(beta-D-gentibiosyl)
      ester, the absence of trans crocetin di-(beta-D-glucosyl) ester in gardenia, and
      its higher content of trans crocetin (beta-D-gentibiosyl) ester and cis crocetin
      di-(beta-D-gentibiosyl) ester. With the same chromatographic method it was
      possible to identify, in a single run, ten glycosidic compounds in saffron
      extracts with a UV/vis pattern similar to that of picrocrocin; among them, 5
      hydroxy-7,7-dimethyl-4,5,6,7-tetrahydro-3H-isobenzofuranone 5-O-beta-D
      gentibioside and 4-hydroxymethyl-3,5,5-trimethyl-cyclohexen-2-one 4-O-beta-D
      gentibioside were tentatively identified for the first time in saffron. Of these
      ten glycosides, only the O-beta-D-gentibiosyl ester of 2-methyl-6-oxo-2,4-hepta
      2,4-dienoic acid was found in gardenia samples, but it was possible to identify
      the iridoid glycoside, geniposide.

PMID- 16448212
TI  - Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress
      inflammatory cell signaling in colon cancer cells.
AB  - Phytochemicals from fruits such as the pomegranate (Punica granatum L) may
      inhibit cancer cell proliferation and apoptosis through the modulation of
      cellular transcription factors and signaling proteins. In previous studies,
      pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced
      apoptosis in HT-29 colon cancer cells. The present study examined the effects of
      PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell
      line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced
      COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract
      (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ
      reduced phosphorylation of the p65 subunit and binding to the NFkappaB response
      element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold,
      whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ
      also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity.
      Therefore, the polyphenolic phytochemicals in the pomegranate can play an
      important role in the modulation of inflammatory cell signaling in colon cancer
      cells.

PMID- 16448215
TI  - The year of the mammoth.

PMID- 16448216
TI  - Determining effective methadone doses for individual opioid-dependent patients.
AB  - BACKGROUND: Randomized clinical trials of methadone maintenance have found that
      on average high daily doses are more effective for reducing heroin use, and
      clinical practice guidelines recommend 60 mg/d as a minimum dosage. Nevertheless,
      many clinicians report that some patients can be stably maintained on lower
      methadone dosages to optimal effect, and clinic dosing practices vary
      substantially. Studies of individual responses to methadone treatment may be more
      easily translated into clinical practice. METHODS AND FINDINGS: A volunteer
      sample of 222 opioid-dependent US veterans initiating methadone treatment was
      prospectively observed over the year after treatment entry. In the 168 who
      achieved at least 1 mo of heroin abstinence, methadone dosages on which patients
      maintained heroin-free urine samples ranged from 1.5 mg to 191.2 mg (median = 69
      mg). Among patients who achieved heroin abstinence, higher methadone dosages were
      predicted by having a diagnosis of posttraumatic stress disorder or depression,
      having a greater number of previous opioid detoxifications, living in a region
      with lower average heroin purity, attending a clinic where counselors discourage
      dosage reductions, and staying in treatment longer. These factors predicted 42%
      of the variance in dosage associated with heroin abstinence. CONCLUSIONS:
      Effective and ineffective methadone dosages overlap substantially. Dosing
      guidelines should focus more heavily on appropriate processes of dosage
      determination rather than solely specifying recommended dosages. To optimize
      therapy, methadone dosages must be titrated until heroin abstinence is achieved.

PMID- 16448217
TI  - Complete mitochondrial genome and phylogeny of Pleistocene mammoth Mammuthus
      primigenius.
AB  - Phylogenetic relationships between the extinct woolly mammoth (Mammuthus
      primigenius), and the Asian (Elephas maximus) and African savanna (Loxodonta
      africana) elephants remain unresolved. Here, we report the sequence of the
      complete mitochondrial genome (16,842 base pairs) of a woolly mammoth extracted
      from permafrost-preserved remains from the Pleistocene epoch--the oldest
      mitochondrial genome sequence determined to date. We demonstrate that well
      preserved mitochondrial genome fragments, as long as approximately 1,600-1700
      base pairs, can be retrieved from pre-Holocene remains of an extinct species.
      Phylogenetic reconstruction of the Elephantinae clade suggests that M.
      primigenius and E. maximus are sister species that diverged soon after their
      common ancestor split from the L. africana lineage. Low nucleotide diversity
      found between independently determined mitochondrial genomic sequences of woolly
      mammoths separated geographically and in time suggests that north-eastern Siberia
      was occupied by a relatively homogeneous population of M. primigenius throughout
      the late Pleistocene.

PMID- 16448218
TI  - A comparison of intrazeolite and solution singlet oxygen Ene reactions of allylic
      alcohols.
AB  - The singlet oxygen ene reactions of four allylic alcohols and for comparison an
      allylic ether have been examined both in solution and in zeolite Y. Bronsted acid
      sites in the zeolite were shown to induce decomposition of several of the allylic
      alcohols. Treatment of the zeolites with pyridine removed these acid sites and
      allowed intrazeolite reactions of the allylic alcohols without interference from
      decomposition. Control reactions with an allylic alcohol that is inert to
      decomposition provided evidence that the presence of pyridine in the zeolite
      labyrinth does not influence the product composition.

PMID- 16448220
TI  - Adipose differentiation related protein induces lipid accumulation and lipid
      droplet formation in hepatic stellate cells.
AB  - The function of adipose differentiation-related protein (ADRP) is known to be the
      uptake of long-chain fatty acids and formation of lipid droplets in lipid
      accumulating cells. We hypothesized that ADRP might stimulate activated hepatic
      stellate cells (HSCs) to accumulate lipids, resulting in their transition to the
      quiescent state. In this study, cultured HSCs in fifth passages isolated from rat
      were infected by adenovirus vector expressing ADRP (Ad.GFP-ADRP), and morphologic
      and functional changes were evaluated in comparison with control HSCs infected by
      recombinant adenovirus-expressing beta-galactosidase (Ad.LacZ). In Ad.GFP-ADRP
      infected cells only, many tiny lipid droplets were apparent in the cytoplasm,
      while the outline of the cells was not changed. The ADRP was detected around the
      lipid droplets. In HSCs with intracellular actin filaments, the staining pattern
      of the filaments before and after infection with Ad.GFP-ADRP or Ad.LacZ did not
      differ. The cell proliferation rate was not influenced by infection with Ad.LacZ
      or Ad.GFP-ADRP. Type I collagen secretion from cells overexpressing ADRP was not
      significantly different from that of Ad.LacZ-infected cells. In our in vitro
      study, ADRP overexpression induced the formation of cytoplasmic lipid droplets in
      activated HSCs but could not convert other characteristics of the activated form
      into those of the quiescent form.

PMID- 16448221
TI  - Selection of a standard culture medium for primary culture of limulus polyphemus
      amebocytes.
AB  - This study provides information relevant to future research aimed at producing
      Limulus Amebocyte Lysate (LAL) in vitro, which would potentially reduce the need
      to harvest and bleed horseshoe crabs as in the current methods of LAL production.
      To address the need for primary culture of horseshoe crab amebocytes, this study
      tested the effects of a variety of standard insect cell culture media on
      amebocyte morphology and viability after 7 d of maintenance. Amebocyte morphology
      was least altered from in vivo form in Grace's Modified Insect Medium, with no
      observed degranulation of cells, as compared to the other media tested. There
      were significant differences in amebocyte viability among the six insect cell
      culture media tested. Grace's Modified Insect Medium sustained viability of 77.2
      +/- 5.1% (mean +/- standard deviation) of amebocytes, followed distantly by
      Grace's Insect Medium with 35.1 +/- 8.7% amebocyte viability. Results indicate
      that Grace's Modified Insect Medium with horseshoe crab serum supplementation was
      the best candidate of the six media tested for future medium optimization for
      Limulus amebocyte requirements.

PMID- 16448222
TI  - Protease activity in protein-free NS0 myeloma cell cultures.
AB  - Zymography of concentrated conditioned medium (CM) from protein-free NS0 myeloma
      cell cultures showed that this cell line produced and released/secreted several
      proteases. Two caseinolytic activities at 45-50 and 90 kDa were identified as
      aspartic acid proteases, and at least two cathepsins of the papain-like cysteine
      protease family with molecular masses of 30-35 kDa were found by gelatin
      zymography. One of these cathepsins was identified as cathepsin L by using an
      enzyme assay exploiting the substrate Z-Phe-Arg-AMC and the inhibitor Z-Phe-Tyr
      t(Bu)-DMK. The aspartic acid and cysteine proteases were active only at acidic pH
      and are therefore not a potential risk for degrading the product or affecting
      cell growth during culture. Secreted proforms of cathepsins may, however, possess
      mitogenic functions, but addition of anti-procathepsin L antibodies to NS0
      cultures did not influence proliferation. The recombinant antibody product was
      not degraded in cell-free CM incubated at pH 7, but when the pH was decreased to
      3.5-4, the aspartic acid proteases degraded the product. Gelatin zymography also
      revealed the presence of several serine proteases in NS0 CM, one at 85 kDa and
      two at 50 kDa, with pH optima close to culture pH. Addition of the serine
      protease inhibitor aprotinin significantly increased the specific proliferation
      rate as compared to the control. In addition to these data, N-terminal amino acid
      sequencing identified two proteins in NS0 CM as the protease inhibitors secretory
      leukocyte protease inhibitor and cystatin C.

PMID- 16448219
TI  - Clock genes of Mammalian cells: practical implications in tissue culture.
AB  - The clock genes family is expressed by all the somatic cells driving central and
      peripheral circadian rhythms through transcription/translation feedback loops.
      The circadian clock provides a local time for a cell and a way to integrate the
      normal environmental changes to smoothly adapt the cellular machinery to new
      conditions. The central circadian rhythm is retained in primary cultures by
      neurons of the suprachiasmatic nuclei. The peripheral circadian rhythms of the
      other somatic cells are progressively dampened down up to loss unless neuronal
      signals of the central clock are provided for re-entrainment. Under typical
      culture conditions (obscurity, 37 +/- 1 degrees C, 5-7% CO(2)), freshly explanted
      peripheral cells harbor chaotic expression of clock genes for 12-14 h and loose,
      coordinated oscillating patterns of clock components. Cells of normal or
      cancerous phenotypes established in culture harbor low levels of clock genes
      idling up to the re-occurrence of new synchronizer signals. Synchronizers are
      physicochemical cues (like thermic oscillations, short-term exposure to high
      concentrations of serum or single medium exchange) able to re-induce molecular
      oscillations of clock genes. The environmental synchronizers are integrated by
      response elements located in the promoter region of period genes that drive the
      central oscillator complex (CLOCK:BMAL1 and NPAS2:BMAL1 heterodimers). Only a few
      cell lines from different species and lineages have been tested for the existence
      or the functioning of a circadian clockwork. The best characterized cell lines
      are the immortalized SCN2.2 neurons of rat suprachiasmatic nuclei for the central
      clock and the Rat-1 fibroblasts or the NIH/3T3 cells for peripheral clocks.
      Isolation methods of fragile cell phenotypes may benefit from research on the
      biological clocks to design improved tissue culture media and new bioassays to
      diagnose pernicious consequences for health of circadian rhythm alterations.

PMID- 16448223
TI  - Establishment of three human breast epithelial cell lines derived from carriers
      of the 999del5 BRCA2 Icelandic founder mutation.
AB  - Germ line mutations in BRCA1 and BRCA2 account for a large proportion of
      inherited breast and ovarian cancer. Both genes are involved in DNA repair by
      homologous recombination and are thought to play a vital role in maintaining
      genomic stability. A major drawback for long-term functional studies of BRCA in
      general and BRCA2 in particular has been a lack of representative human breast
      epithelial cell lines. In the present study, we have established three cell lines
      from two patients harboring the 999del5 germ line founder mutation in the BRCA2
      gene. Primary cultures were established from cellular outgrowth of explanted
      tissue and subsequently transfected with a retroviral construct containing the
      HPV-16 E6 and E7 oncogenes. Paired cancer-derived and normal-derived cell lines
      were established from one patient referred to as BRCA2-999del5-2T and BRCA2
      999del5-2N, respectively. In addition, one cell line was derived from cancer
      associated normal tissue from another patient referred to as BRCA2-999del5-1N.
      All three cell lines showed characteristics of breast epithelial cells as
      evidenced by expression of breast epithelial specific cytokeratins. Cytogenetic
      analysis showed marked chromosomal instability with tetraploidy and frequent
      telomeric associations. In conclusion, we have established three breast
      epithelial cell lines from two patients carrying the BRCA2 Icelandic 999del5
      founder mutation. These cell lines form the basis for further studies on
      carcinogenesis and malignant progression of breast cancer on a defined genetic
      background.

PMID- 16448224
TI  - Adult rat spinal cord culture on an organosilane surface in a novel serum-free
      medium.
AB  - In this study, we have documented by morphological analysis, immunocytochemistry,
      and electrophysiology, the development of a culture system that promotes the
      growth and long-term survival of dissociated adult rat spinal cord neurons. This
      system comprises a patternable, nonbiological, cell growth-promoting organosilane
      substrate coated on a glass surface and an empirically derived novel serum-free
      medium, supplemented with specific growth factors (acidic fibroblast growth
      factor, heparin sulfate, neurotrophin-3, brain-derived neurotrophic factor, glial
      derived neurotrophic factor, cardiotrophin-1, and vitronectin). Neurons were
      characterized by immunoreactivity for neurofilament 150, neuron-specific enolase,
      Islet-1 antibodies, electrophysiology, and the cultures were maintained for 4-6
      wk. This culture system could be a useful tool for the study of adult mammalian
      spinal neurons in a functional in vitro system.

PMID- 16448225
TI  - Melittin-induced membrane permeability: a nonosmotic mechanism of cell death.
AB  - Derived from honeybees, melittin is a 26-amino acid, alpha-helical, membrane
      attack protein that efficiently kills mammalian cells. To investigate the
      contribution of colloid-osmotic effects to the mechanism of cell death, we
      studied the effect of melittin on lymphocyte membrane permeability and cell
      volumes. Melittin concentrations of 0.5 to 2.0 microM induced release of membrane
      permeability markers without total disruption of the cell membrane. At these
      melittin concentrations, electrical-impedance cytometry demonstrated melittin
      induced changes in red blood cell volumes (P<0.01), but no change in lymphocyte
      cell volumes (P>0.05). Streaming video microscopy, obtaining images of melittin
      treated lymphocytes at 80-ms intervals, demonstrated a loss of optical density
      (P<0.001) suggesting a flattening of the cell but no significant increase in cell
      perimeter (P>0.05). Real-time multiparameter flow cytometry of melittin-treated
      lymphocytes confirmed simultaneous loss of the cytoplasmic marker, calcein, and
      uptake of the DNA dye, ethidium homodimer, but demonstrated no increase in
      forward light scatter. Transmission-electron microscopy of melittin-treated
      lymphocytes showed normal cell volumes but discontinuities in the cell membrane
      suggesting direct membrane toxicity. We conclude that melittin causes lymphocyte
      death by a "leaky patch" mechanism that is independent of colloid-osmotic
      effects.

PMID- 16448227
TI  - Backward orthodontics?

PMID- 16448226
TI  - Self-renewal and differentiation of mouse embryonic stem cells as measured by Oct
      4 gene expression: effects of lif, serum-free medium, retinoic acid, and dbcAMP.
AB  - In this study we examined the interplay between serum, leukemia inhibitory factor
      (LIF), retinoic acid, and dibutyrl cyclic adenosine monophosphate (dbcAMP) in
      affecting IOUD2 embryonic stem cell self-renewal and differentiation as assessed
      by Oct 4 expression, and cell proliferation as measured by total cell protein.
      Removal of LIF, reduced levels of fetal calf serum (FCS), and addition of
      retinoic acid all induced embryonic stem cell differentiation as measured by
      reduced Oct 4 expression. Lower levels of retinoic acid (0.1-10 nM) promoted the
      formation of epithelial-like cells, whereas higher levels (100-10,000 nM) favored
      differentiation into fibroblastic-like cells. The effects of dbcAMP varied with
      the presence or absence of FCS and LIF and the concentration of dbcAMP. In FCS
      containing media, a low level of dbcAMP (100 microM) increased self-renewal in
      the absence of LIF, but it had no effect in its presence. In contrast, at higher
      concentrations (1,000 microM dbcAMP), regardless of LIF, differentiation was
      promoted. A similar effect of dbcAMP was seen in the presence of retinoic acid.
      In media without FCS but with serum replacement supplements, there was no effect
      of dbcAMP. This study shows that the Oct 4 expression system of IOUD2 cells
      provides a novel, simple method for quantifying cellular differentiation.

PMID- 16448229
TI  - Two- and three-dimensional orthodontic imaging using limited cone beam-computed
      tomography.
AB  - Considerable progress has been made in diagnostic, medical imaging devices such
      as computed tomography (CT). However, these devices are not used routinely in
      dentistry and orthodontics because of high cost, large space requirements and the
      high amount of radiation involved. A device using computed tomography technology
      has been developed for dental use called a limited cone beam dental compact-CT
      (3DX). The aim of this article is to demonstrate the usefulness of 3DX imaging
      for orthodontic diagnosis and treatment planning. We present three cases: (1) one
      case shows delayed eruption of the upper left second premolar, (2) the second
      case shows severe impaction of a maxillary second bicuspid; and (3) the third
      case shows temporomandibular joint disorder (TMD). In the tooth impaction cases,
      the CT images provided more precise information than conventional radiographic
      images such as improved observation of the long axis of the tooth, root
      condition, and overlap with bone. In the TMD case, clear and detailed
      temporomandibular joint images were observed and pre- and posttreatment condylar
      positions were easily compared. We conclude that 3DX images provide useful
      information for orthodontic diagnosis and treatment planning.

PMID- 16448230
TI  - Prediction of maxillary third molar impaction in adolescent orthodontic patients.
AB  - The purpose of this study was to identify risk factors for maxillary third molar
      impaction in adolescent orthodontic patients. Radiographs made before treatment
      (T1) and after treatment (T2) and at a minimum of 10 years postretention (T3) of
      132 patients that allowed accurate diagnosis of impaction vs eruption of one or
      both maxillary third molars were evaluated. Although univariate logistic
      regression revealed that the decision to extract premolars reduced the risk of
      impaction by 76% (P < .01), this parameter was not included in the final
      prediction model at T1. Multiple logistic regression analyses revealed that third
      molar impaction could be predicted at T1 according to the size of the retromolar
      space and the amount of mesial molar movement that will occur during active
      appliance therapy, reducing the risk of impaction by 22% and 34% for every
      millimeter increase in distance, respectively (P < .01). At T2, multiple logistic
      regression revealed that the odds of impaction were more than 60 times higher (P
      < .01) if the third molar was angulated mesially as compared with less than 30
      degrees distally relative to the occlusal plane and almost five times (P < .05)
      higher if the third molar was angulated more than 30 degrees distally as compared
      with less than 30 degrees distally. Similar analyses at T2 showed 29% reduced
      risk of impaction for every millimeter increase in retromolar space and 18%
      reduced risk for every degree increase in angle MP/SN (P < .01).

PMID- 16448231
TI  - Root resorption after orthodontic intrusion and extrusion: an intraindividual
      study.
AB  - The aim of this investigation was to compare root resorption in the same
      individual after application of continuous intrusive and extrusive forces. In
      nine patients (mean age 15.3 years), the maxillary first premolars were randomly
      intruded or extruded with a continuous force of 100 cN for eight weeks. Eleven
      maxillary first premolars from six randomly selected orthodontic patients served
      as controls. Root resorption was determined using scanning electron microscopy.
      Quantitative assessment of the percentage of resorbed area of the total root
      surface was performed on composite micrographs. The severity of root resorption
      was also assessed by visual scoring of the roots. Root resorption mainly occurred
      at the apical part of the roots in both experimental groups. A significant
      difference in root resorption was found between the intruded and the control
      teeth (P = .006) but not between the extruded and the control teeth. However, the
      mesial and distal root surfaces showed resorption on 5.78 +/- 3.86% of the root
      surface of the intruded teeth and 1.28 +/- 1.24% of the root surface of the
      extruded teeth, and this difference was significant (P = .004). In addition, a
      large individual variation was found. From this study, it can be concluded that
      intrusion of teeth causes about four times more root resorption than extrusion.
      Because the amount of root resorption due to intrusion or extrusion in the same
      patient is correlated, every clinician should be aware that the extrusion of
      teeth might also cause root resorption in susceptible patients.

PMID- 16448232
TI  - Apical root resorption six and 12 months after initiation of fixed orthodontic
      appliance therapy.
AB  - The low explained variance of identified risk factors for apical root resorption
      in orthodontic patients suggests effects of parameters related to individual
      predisposition. Our purpose was to explore this hypothesis. We evaluated
      standardized periapical radiographs of the maxillary incisors made before
      treatment (T1) as well as at about six and 12 months after bracket placement (T2
      and T3) of 247 patients aged 10.1 to 57.1 years at T1. The radiographs were
      converted to digital images, and commercially available software was used to
      correct for differences in projection. The results showed that 20.2%, 7.7%, and
      5.3% of the patients had > or =1 tooth with >2.0, 3.0, and 4.0 mm resorption at
      T3, respectively. Pearson's correlation revealed an association between
      resorption from T1 to T2 and from T2 to T3 (P < .01). The risk of > or =1 tooth
      with >1.0 mm resorption from T2 to T3 was 3.8 times higher (95% CI 2.4-6.0) in
      patients with > or =1 tooth with >1.0 mm from T1 to T2 than in those without.
      Also, resorption was more pronounced (P < .001) from T2 to T3 in patients with >
      or =1 tooth with >1.0 mm and >2.0 resorption from T1 to T2 than in those without.
      The explained variance of identified risk factors was <10%. Orthodontic patients
      with detectable root resorption during the first six months of active treatment
      are more likely to experience resorption in the following six-month period than
      those without.

PMID- 16448233
TI  - Mandibular growth in subjects with infraoccluded deciduous molars: a
      superimposition study.
AB  - The aim of this longitudinal cephalometric study was to analyze the growth
      characteristics of the mandible in subjects with infraocclusion of the mandibular
      deciduous molars. A group of 28 subjects with bilateral infraocclusion of
      mandibular deciduous molars (IG) were enrolled in a prospective longitudinal
      study on the growth characteristics of the mandible and compared with a control
      group (CG) of 28 subjects. Lateral cephalograms were collected in both groups at
      T1 and at T2, after a mean 19-month interval in the IG and after a mean 16-month
      interval in the CG. All subjects were observed in the early mixed dentition
      before the pubertal peak and did not receive any orthodontic treatment during the
      observation interval. Cephalometric analysis at T1 and superimposition of
      tracings at T1 and T2 were performed, and statistical comparisons between the two
      groups were carried out by means of independent sample t-tests. Discriminant
      analysis on the superimposition data identified Co-Gn angle (angle formed by line
      Co-Gn at T1 and at T2) as the single discriminant variable between IG and CG.
      There were significant differences between the two groups as to morphological
      changes of the mandible and direction of condylar growth, thus demonstrating
      anterior growth rotation of the mandible in subjects with infraocclusion. Because
      of the high levels of alveolar bone turnover and remodeling in anterior rotating
      mandibles, this study suggested that skeletal growth characteristics of the
      mandible may influence the clinical expression of infraocclusion.

PMID- 16448234
TI  - Association between growth stunting with dental development and skeletal
      maturation stage.
AB  - The aim of this study was to determine the influence of growth stunting on the
      maturation stage of the medium phalanx of the third finger (MP3) and the dental
      development of the left mandibular canine in 280 high school children (140
      stunted and 140 normal controls; equally distributed by sex) between 9.5 and 16.5
      years of age, from a representative Peruvian school. Periapical radiographs of
      the MP3 from the left hand were used to determine the skeletal maturity stage,
      according to an adaptation of the Hagg and Taranger method. Panoramic radiographs
      were used to determine the dental maturity stage of the lower left canine,
      according to Demirjian method. Stunting was determined by relating height and
      age, according to the World Health Organization recommendations. There was no
      statistically significant difference in the skeletal maturation stage (P = .134)
      and the dental development stage (P = .497) according to nutritional status, even
      when considering different age groups (P > .183). A high correlation (r = 0.85)
      was found between both maturity indicators regardless of the nutritional status
      (growth stunted, r = 0.855 and normal controls, r = 0.863) or sex (boys, r =
      0.809 and girls, r = 0.892). When skeletal level was considered, correlations
      values were similar between advanced (r = 0.903) and average (r = 0.895) maturers
      but lower (r = 0.751) for delayed maturers. Growth stunting was not associated
      with dental development and skeletal maturity stages in Peruvian school children.

PMID- 16448235
TI  - Dental and alveolar arch widths in normal occlusion, class II division 1 and
      class II division 2.
AB  - The aim of this study was to compare the transverse dimensions of the dental
      arches and alveolar arches in the canine, premolar, and molar regions of Class II
      division 1 and Class II division 2 malocclusion groups with normal occlusion
      subjects. This study was performed using measurements on dental casts of 150
      normal occlusion (mean age: 21.6 +/- 2.6 years), 106 Class II division 1 (mean
      age: 17.2 +/- 2.4 years), and 108 Class II division 2 (mean age: 18.5 +/- 2.9
      years) malocclusion subjects. Independent-samples t-test was applied for
      comparisons of the groups. These findings indicate that the maxillary
      interpremolar width, maxillary canine, premolar and molar alveolar widths, and
      mandibular premolar and molar alveolar widths were significantly narrower in
      subjects with Class II division 1 malocclusion than in the normal occlusion
      sample. The maxillary interpremolar width, canine and premolar alveolar widths,
      and all mandibular alveolar widths were significantly narrower in the Class II
      division 2 group than in the normal occlusion sample. The mandibular intercanine
      and interpremolar widths were narrower and the maxillary intermolar width
      measurement was larger in the Class II division 2 subjects when compared with the
      Class II division 1 subjects. Maxillary molar teeth in subjects with Class II
      division 1 malocclusions tend to incline to the buccal to compensate the
      insufficient alveolar base. For that reason, rapid maxillary expansion rather
      than slow expansion may be considered before or during the treatment of Class II
      division 1 patients.

PMID- 16448236
TI  - Arch width changes in extraction and nonextraction treatment in class I patients.
AB  - The aim of this retrospective study was to examine the dental arch width changes
      of extraction and nonextraction treatment in Class I patients. The study was
      performed on pretreatment and posttreatment dental casts of 60 patients (30
      extraction and 30 nonextraction). The mean ages were 14.3 +/- 2.02 years for the
      extraction group and 14.1 +/- 2.9 years for the nonextraction group. The
      maxillary and mandibular crowding was -6.7 +/- 3.1 and -6.3 +/- 2.8 mm for the
      extraction group and -4.5 +/- 3.6 and -2.1 +/- 3.5 mm for the nonextraction
      group, respectively. The intercanine and intermolar arch width measurements were
      measured using a digital caliper. Paired samples t-test was used to evaluate the
      treatment changes within each group. To compare the changes between groups,
      independent samples t-test was performed. At the start of treatment, the
      maxillary and the mandibular intercanine and intermolar widths of both groups did
      not differ statistically. At the end of treatment, maxillary and mandibular
      intercanine widths of both groups increased significantly. The mandibular
      intermolar width decreased significantly for the extraction group and the
      maxillary intermolar width increased significantly for the nonextraction group.
      The decrease in maxillary intermolar width for the extraction group and the
      increase in mandibular intermolar width for the nonextraction group were not
      significantly different. No differences were observed between the groups in
      maxillary and mandibular intercanine widths. Maxillary and mandibular intermolar
      width indicated a significantly larger value in the nonextraction group than that
      in the extraction group.

PMID- 16448237
TI  - Preferences for facial profiles between Mexican Americans and Caucasians.
AB  - The objective of this study was to determine differences between Mexican American
      and Caucasian judges in the acceptability of lip protrusion in computer
      animations of two male and two female persons of Mexican descent. Thirty
      Caucasians and 30 Mexican Americans of varying age, sex, education, and level of
      acculturation responded to facial profile computer animations that moved lips
      from an extreme protrusive to an extreme retrusive position. Judges were asked to
      complete two tasks: (1) to press the mouse button when the image was perceived to
      be most pleasing (MP) and (2) to determine the boundaries of a zone of
      acceptability (ZA) of lip protrusion by pressing the mouse button when the moving
      image became acceptable and releasing it when the image of the protrusion became
      unacceptable. In general, Mexican Americans preferred upper or lower lip
      positions to be less protrusive than did Caucasians. Larger mean ZAs for both
      upper and lower lip positions with male computer animation images and lower lip
      position for female computer animation images were found among Caucasians when
      compared with low-acculturated Mexican Americans. A significant mean difference
      in midpoint of acceptability (MA) for lip position between Caucasians and low
      acculturated Mexican Americans was observed for both upper and lower lip position
      with female computer animation images.

PMID- 16448238
TI  - Soft and hard tissue changes after bimaxillary surgery in Chinese Class III
      patients.
AB  - Cephalometric studies have shown that the Chinese race tends to have a greater
      preponderance of skeletal Class III malocclusion. It has also been reported that
      the soft tissue response to hard tissue movement varies among racial types. The
      aims of this retrospective cephalometric study were to assess the results of
      bimaxillary surgery on Chinese subjects presenting with Class III malocclusions
      and to evaluate the correlation between soft and hard tissue change. The sample
      consisted of 34 Chinese patients treated with bilateral sagittal split osteotomy
      and Le Fort I advancement. Lateral cephalograms were taken immediately before
      surgery and at least six months after surgery. Soft and hard tissue changes were
      recorded by computer-supported measurements of presurgical and postsurgical
      lateral cephalograms. Linear regression procedures were used to assess the degree
      of correlation in terms of soft to hard tissue changes between the two
      cephalograms. The results showed that there was normalization of the
      cephalometric variables after surgery. Mandibular soft and hard tissue movements
      showed a strong correlation in the horizontal direction and a moderate
      correlation in the vertical direction. Maxillary soft and hard tissue movement
      showed a moderate to weak correlation in both the horizontal and vertical
      directions. The ratios of soft to hard tissue movements derived from this study
      would contribute to the database for planning prediction.

PMID- 16448239
TI  - Accuracy of a LeFort I maxillary osteotomy.
AB  - An optimal outcome of combined surgery and orthodontics involving the maxilla is
      dependent on many factors. Accurate placement of the maxilla by the surgical team
      is ultimately of paramount importance. The aim of this retrospective study was to
      evaluate the accuracy of LeFort I maxillary osteotomy with respect to the
      presurgical prediction. The sample comprised 42 patients (33 females, nine males)
      who had undergone LeFort I osteotomy procedure alone or in combination with a
      mandibular osteotomy with or without genioplasty. Tracings of presurgical and
      immediate postsurgical lateral cephalograms and surgical predictions were
      digitized and compared using Quick Ceph software analysis. Vertical and
      horizontal measurements to various skeletal landmarks were used to assess the
      discrepancy between the predicted maxillary position and the actual postsurgical
      result. Statistically significant differences were found between the predicted
      and actual postsurgical maxillary molar vertical position, and significant
      differences were also found for the palatal plane angular measurements. Two
      surgical teams were compared, and surgical team 1 had significantly less
      variation in the surgical outcomes than did surgical team 2. When single-jaw and
      bimaxillary surgery were compared, no significant differences were found.
      Similarly, there were no statistically significant differences found when
      assessing the primary direction of movement (impaction vs downgraft vs
      advancement). Overall, 66% of the results were within two mm of prediction and
      26% of the results were within one mm of prediction. A LeFort I maxillary
      osteotomy can be an accurate procedure with a wide range of discrepancy.

PMID- 16448240
TI  - The Relationship between molar dentoalveolar and craniofacial heights.
AB  - Excessive vertical growth of the posterior dentoalveolar region has been
      implicated in the etiology of the so-called long-face syndrome. In this study, we
      tested the hypothesis that molar dentoalveolar heights are positively related to
      vertical craniofacial features. Cephalometric measurements obtained from 82 adult
      subjects were entered as independent variables in a multiple regression model.
      Maxillary and mandibular molar dentoalveolar heights were entered as dependent
      variables. Approximately 70% of the total variance was explained by anterior
      lower facial height (ANS-Me) and the mandibular palatal plane angle (PP-MP).
      Increases of ANS-Me and PP-MP had opposite effects on the amount of molar
      dentoalveolar heights. The lowest values of molar dentoalveolar heights were
      found in subjects with a small ANS-Me distance but with a wide PP-MP angle. The
      findings suggest that individuals with a marked divergence of the jaws may also
      have a reduced molar dentoalveolar vertical development.

PMID- 16448241
TI  - Class II malocclusion with maxillary protrusion from the deciduous through the
      mixed dentition: a longitudinal study.
AB  - The aim of this study was to analyze the skeletal characteristics of Class II
      malocclusion with maxillary protrusion in the deciduous dentition and to describe
      the growth features of this type of skeletal imbalance during the transition from
      the deciduous through the mixed dentition. A group of 17 subjects having skeletal
      Class II malocclusions in the deciduous dentition due to maxillary protrusion was
      compared with a control group of 30 untreated subjects with ideal occlusion at
      the same stage of development. Both groups were observed for the first time in
      the deciduous dentition (T(1)) and followed during the transition from the
      deciduous to the mixed dentition (T(2)). During this time no orthodontic
      treatment was provided. Lateral cephalograms were taken for all subjects at T(1)
      and T(2). A cephalometric analysis was performed based on a reference system that
      consisted of two perpendicular lines traced through stable basicranical
      structures. The results indicate that a Class II skeletal pattern due to a
      maxillary protrusion is established early in the deciduous dentition and remains
      unmodified in the transition to the mixed dentition. The maxilla appeared to be
      displaced forward in Class II subjects, whereas the mandibles of the Class I and
      Class II subjects did not show any significant differences at this stage of
      growth. In the passage from the deciduous through the mixed dentition, Class I
      and Class II subjects showed growth increments that were not significantly
      different from each other. Sucking habits appeared to be correlated with the
      skeletal maxillary protrusion.

PMID- 16448242
TI  - Anchorage control in bioprogressive vs straight-wire treatment.
AB  - Orthodontic techniques with different concepts and philosophies have emerged to
      provide adequate anchorage control. The purpose of this study was to compare the
      effectiveness of the Bioprogressive and Straight-wire techniques in the control
      of lower anchorage. Data were obtained from the records of 40 patients presenting
      Class I and II malocclusions treated with first bicuspid extractions. One group
      of 20 patients was treated with a utility arch used to set up cortical anchorage
      in the lower arch and sectional retraction mechanics for space closure. The
      second group was treated with straight wire with a preadjusted appliance system.
      Treatment evaluation revealed no significant between-group differences in the
      amount of skeletal growth relative to cranial base and lower mesial movement of
      first molars. Mean lower anchorage loss was 3.1 mm in the Bioprogressive patients
      and four mm in the Straight-wire patients. The apical base change was the most
      important component to molar correction. Although cortical anchorage did not
      impede lower molar movement, it was no less effective in controlling molar
      movement with a partial appliance than was the fully banded Straight-wire
      appliance.

PMID- 16448243
TI  - Expression of Notch1 and Math1 in mandibular condyle cartilage in neonatal mice.
AB  - On the basis of the cellular morphological changes in the cartilaginous area, the
      mandibular condylar cartilage is histopathologically composed of four different
      cell layers--fibrous, proliferative, maturative, and hypertrophic. Reaction for
      Notch1 was present in the hypertrophic cells only. However, Math1 was locally
      distributed in the hypertrophic layer and partially in the proliferative layer.
      The expression patterns of Notch1 and Math1 were slightly different. These
      results suggest that the morphogenesis regulation factors of Notch1 and Math1 may
      play some role in mandibular condylar cartilage. Positive reactions to
      osteopontin, as a control, were detected in the cytoplasm of all layers, although
      they varied from published data.

PMID- 16448244
TI  - Standardizing interarch tooth-size harmony in a Syrian population.
AB  - The Bolton analysis is considered to be a good indicator for evaluating the
      degree of intermaxillary tooth-size harmony, but the possibility of ethnic
      variation of these values should be examined. Thus, the aim of this study was to
      calculate both the anterior and overall ratios of mandibular and maxillary tooth
      sizes for a Syrian sample of harmonious permanent dentitions and to compare these
      ratios with the data from the Bolton and the Michigan studies. In plaster models
      of 55 Syrian patients (11-22 years) with neutral occlusion (Angle Class I),
      harmonious overjet and overbite, no reduction of mesiodistal tooth width or
      missing teeth, the mesiodistal widths of each tooth from the incisors to the
      first permanent molars were measured in both arches. In the statistical data
      analysis, the anterior and overall ratios were calculated according to Bolton.
      The results for the anterior ratio (78.99 +/- 2.18) and the overall ratio (92.26
      +/- 2.06) showed no statistically significant differences by sex (P > .48). These
      values and the degree of variation were similar to the original data by Bolton.
      Both studies differed considerably from the values of the anterior ratio found in
      the Michigan University study, which also shows a higher degree of variability.
      Nevertheless, the overall ratios of all three studies were very similar.
      Therefore, the interarch tooth-size analysis and values for a harmonious
      dentition developed by Bolton can also be transferred to an Arabian or at least a
      Syrian population.

PMID- 16448245
TI  - Long-term clinical failure rate of molar tubes bonded with a self-etching primer.
AB  - The purpose of this study was to assess the long-term in vivo failure rate of
      tubes bonded to first and second molars with a self-etching primer (SEF). A total
      of 810 molar tubes (414 first molar and 396 second molar) were bonded on 135
      patients (56 male, 79 female; mean age 14 years) with the 3M Transbond Plus Self
      Etching Primer. The first-time failures of the tubes were recorded for a mean
      period of 26 months (range 23-29 months). Failure rates per jaw (maxilla
      mandible), tooth (first and second molar), and quadrant (left, right) were
      analyzed with the chi(2) at alpha = 0.05 level of significance. Significant
      differences were found in the failure rate between first and second molars (9.66%
      vs 20%, respectively) as well as maxillary and mandibular molars (7.5% vs 21%,
      respectively). The combined, total failure rate for first and second molars was
      14.80%. No difference was found between male and female failure rates for the
      molar tubes. First-molar tubes bonded with an SEF may show failure rates
      comparable with those reported in the literature for tubes bonded with
      conventional acid etching.

PMID- 16448246
TI  - Measurement techniques predicting the effectiveness of an oral appliance for
      obstructive sleep apnea hypopnea syndrome.
AB  - The purpose of this study is to determine the measurement techniques that can
      predict the effectiveness of an oral appliance (OA) for the treatment of patients
      with obstructive sleep apnea hypopnea syndrome (OSAHS). Split-night
      polysomnography and esophageal pressure (Pes) were recorded, and cephalometric
      tracings were superimposed for 25 OSAHS patients. The patients were classified
      into good and poor responders according to their apnea hypopnea index (AHI) and
      mean nadir Pes. When the degree of anterior displacement of the mandible was
      expressed by vector resolution, it was significantly different between the good
      and poor responders, whereas there was no significant difference in downward and
      total mandibular displacement between the two groups. Among the good responders
      evaluated on the basis of mean nadir Pes, their apnea index, hypopnea index, and
      mean nadir Pes were significantly different. However, AHI alone cannot predict
      the effectiveness of OA treatment. Good responders defined by mean nadir Pes also
      had short soft palates and a wide pharyngeal airway space. Conversely, no
      significant differences were observed in these parameters when good responders
      and poor responders are defined by AHI. Logistic regression analysis revealed
      that the degree of anterior displacement of the mandible showed a significant
      odds ratio of 1.97. In conclusion, evaluations based on Pes and analyses of the
      mandibular displacement expressed by vector resolution using a cephalometric
      superimposition technique can provide important clinical information in
      evaluation measurements and may be useful for the prediction of the efficacy of
      OA treatment for patients with OSAHS.

PMID- 16448247
TI  - Uvulo-glosso-pharyngeal dimensions in different anteroposterior skeletal
      patterns.
AB  - The aim of this study was to investigate the uvulo-glosso-pharyngeal dimensions
      in subjects with different anteroposterior jaw relationship. Cephalometric
      radiograph of 90 subjects (45 females and 45 males, aged 14-17 years) were
      divided into three groups according to the ANB angle, ie, group 1, skeletal Class
      I (ANB angle 1-5); group 2, skeletal Class II (ANB angle >5); and group 3,
      skeletal Class III (ANB angle <1). In addition, each group was divided into two
      subgroups according to sex. Statistical analysis was undertaken using analysis of
      variance and least significant difference test. Pearson's Correlation test was
      also performed. Sex differences were found in Class I and III subjects. No sex
      differences were detected in Class II subjects. On average, tongue length was
      significantly shorter in Class III subjects (P < .05), tongue height was reduced
      in Class II female subjects, the soft palate was thicker in Class III females and
      the vertical airway length (VAL) was reduced in Class II male subjects (P < .01).
      In Class II subjects, the hyoid bone was closer to the mandible vertically and to
      C3 horizontally compared with Class I (P < .01) and Class III (P < .001) male
      subjects. Anteroposterior skeletal pattern showed a weak, but significant
      correlation with inferior pharyngeal airway space (R = -0.24, P = .024), vertical
      position of hyoid bone in relation to mandibular plane (R = -0.26, P = .014), and
      anteroposterior position of hyoid bone in relation to C3 (R = -0.561, P = .000).
      In conclusion, uvulo-glosso-pharyngeal dimensions are affected by anteroposterior
      skeletal pattern.

PMID- 16448248
TI  - A comparison of two indirect bonding adhesives.
AB  - The aim of this study was to compare and evaluate the clinical failure rates of
      the chemically cured composite bonding resin Maximum Cure (MC) and the flowable
      light-cured resin Filtek Flow (FF) when used in an indirect bonding technique. A
      total of 112 consecutive patients satisfying the selection criteria were assigned
      to alternating groups in a split-mouth study design. In Group 1, the maxillary
      right and mandibular left quadrants were indirectly bonded using MC adhesive,
      whereas the contralateral quadrants were bonded using FF adhesive. In Group 2,
      the sides bonded were opposite to those in Group 1. One patient was lost from
      group 1, so the adjacent patient from group 2 was excluded. Over a six-month
      observation period, all loose brackets were recorded and the data compared with a
      Wilcoxon signed ranks test. Of the 2468 brackets placed, 36 with the MC adhesive
      came loose (2.9% failure rate) compared with 30 in the FF group (2.4% failure
      rate, P = .95). In the maxillary arch, 12 brackets from the MC quadrants came
      loose vs 24 in the FF (P = .02). In the mandibular arch, 24 brackets from the MC
      quadrants came loose during the six-month observation period compared with six
      from the FF quadrants (P = .03). These results suggest that both adhesives
      examined in this study (MC and FF) were suitable for the indirect bonding of
      brackets. The failure rates were low for both adhesives, so either could be
      recommended for clinical use, the choice being dictated more by operator
      preference.

PMID- 16448249
TI  - Insect detection of small targets moving in visual clutter.
AB  - Detection of targets that move within visual clutter is a common task for animals
      searching for prey or conspecifics, a task made even more difficult when a moving
      pursuer needs to analyze targets against the motion of background texture
      (clutter). Despite the limited optical acuity of the compound eye of insects,
      this challenging task seems to have been solved by their tiny visual system. Here
      we describe neurons found in the male hoverfly, Eristalis tenax, that respond
      selectively to small moving targets. Although many of these target neurons are
      inhibited by the motion of a background pattern, others respond to target motion
      within the receptive field under a surprisingly large range of background motion
      stimuli. Some neurons respond whether or not there is a speed differential
      between target and background. Analysis of responses to very small targets
      (smaller than the size of the visual field of single photoreceptors) or those
      targets with reduced contrast shows that these neurons have extraordinarily high
      contrast sensitivity. Our data suggest that rejection of background motion may
      result from extreme selectivity for small targets contrasting against local
      patches of the background, combined with this high sensitivity, such that
      background patterns rarely contain features that satisfactorily drive the neuron.

PMID- 16448250
TI  - Metallurgical characterization of orthodontic brackets produced by Metal
      Injection Molding (MIM).
AB  - The aim of this study was to investigate the bonding base surface morphology,
      alloy type, microstructure, and hardness of four types of orthodontic brackets
      produced by Metal Injection Molding technology (Discovery, Extremo, Freedom, and
      Topic). The bonding base morphology of the brackets was evaluated by scanning
      electron microscopy (SEM). Brackets from each manufacturer were embedded in epoxy
      resin, and after metallographic grinding, polishing and coating were analyzed by
      x-ray energy-dispersive spectroscopic (EDS) microanalysis to assess their
      elemental composition. Then, the brackets were subjected to metallographic
      etching to reveal their metallurgical structure. The same specimen surfaces were
      repolished and used for Vickers microhardness measurements. The results were
      statistically analyzed with one-way analysis of variance and Student-Newman-Keuls
      multiple comparison test at the 0.05 level of significance. The findings of SEM
      observations showed a great variability in the base morphology design among the
      brackets tested. The x-ray EDS analysis demonstrated that each bracket was
      manufactured from different ferrous or Co-based alloys. Metallographic analysis
      showed the presence of a large grain size for the Discovery, Freedom, and Topic
      brackets and a much finer grain size for the Extremo bracket. Vickers hardness
      showed great variations among the brackets (Topic: 287 +/- 16, Freedom: 248 +/-
      13, Discovery: 214 +/- 12, and Extremo: 154 +/- 9). The results of this study
      showed that there are significant differences in the base morphology,
      composition, microstructure, and microhardness among the brackets tested, which
      may anticipate significant clinical implications.

PMID- 16448251
TI  - Waterline disinfectant effect on the shear bond strength of orthodontic brackets.
AB  - The purpose of this study was to determine whether the use of an iodine compound
      for disinfecting the waterlines in dental units has an effect on the shear bond
      strength of orthodontic brackets bonded to enamel. Forty molar teeth were divided
      randomly into two groups- group 1 control: twenty teeth were etched for 15
      seconds with 35% phosphoric acid, washed with a distilled water spray for 10
      seconds, stored in distilled water for 5 minutes, dried to a chalky white
      appearance, and the sealant applied to the etched surface; group 2 experimental:
      twenty teeth were etched for 15 seconds with 35% phosphoric acid and washed for
      10 seconds with water containing iodine. The teeth were stored for five minutes
      in the iodinated water, dried to a chalky white appearance, and the sealant
      applied to the etched surface as in the control group. Precoated brackets were
      placed on all the teeth and light cured for 20 seconds. All teeth were debonded
      within 30 minutes from the initial time of bonding. The t-test results (t = 1.74)
      indicated that there were no significant (P = .09) differences in the shear bond
      strengths of the teeth that were washed and immersed in the iodine solution and
      the control group in which distilled water was used. The mean shear bond
      strengths for the two groups were 6.5 +/- 3.5 MPa and 4.7 +/- 3.1 MPa,
      respectively.

PMID- 16448252
TI  - Effects of a chlorhexidine varnish on shear bond strength in indirect bonding.
AB  - The purpose of this study was to evaluate the effects of an antimicrobial varnish
      on the shear bond strength (SBS) of metallic orthodontic brackets bonded with an
      indirect bonding resin. For this purpose, 60 noncarious human premolars were
      divided into three equal groups. Group 1 was an indirect bonding control group
      and, after acid etching of the enamel, the brackets were indirectly bonded to the
      teeth with an indirect bonding resin. In group 2, before bonding, an
      antimicrobial varnish was painted on the etched enamel and indirect bonding was
      carried out as in group 1. In group 3, Transbond MIP primer and the antimicrobial
      varnish were thoroughly mixed in a 1:2 proportion, applied to the enamel surface,
      light cured for 20 seconds, and the brackets were direct bonded. A universal
      testing machine was used to determine the maximum load necessary to debond the
      brackets, the SBS values recorded, and the adhesive remnant index scores
      determined. Data were analyzed using analysis of variance (ANOVA), Tukey HSD, and
      chi-square tests. Results of ANOVA revealed statistically significant differences
      in the SBS among the various groups tested (P < .05). Indirect bonding of
      brackets with Sondhi Rapid Set after the application of the antimicrobial varnish
      showed significantly lower SBS when compared with both the group 2, indirect
      bonding control group, and the group 3, direct bonded-antimicrobial varnish
      group.

PMID- 16448253
TI  - Friction of conventional and self-ligating brackets using a 10 bracket model.
AB  - The friction generated by various bracket-archwire combinations previously has
      been studied using in vitro testing models that included only one or three
      brackets. This study was performed using a specially designed apparatus that
      included 10 aligned brackets to compare the frictional resistance generated by
      conventional stainless steel brackets, self-ligating Damon SL II brackets and
      Time Plus brackets coupled with stainless steel, nickel-titanium and beta
      titanium archwires. All brackets had a 0.022-inch slot, and five different sizes
      of orthodontic wire alloys used. Each bracket-archwire combination was tested 10
      times, and each test was performed with a new bracket-wire sample. Time Plus self
      ligating brackets generated significantly lower friction than both the Damon SL
      II self-ligating brackets and Victory brackets. However, the analysis of the
      various bracket-archwire combinations showed that Damon SL II brackets generated
      significantly lower friction than the other brackets when tested with round wires
      and significantly higher friction than Time Plus when tested with rectangular
      archwires. Beta-titanium archwires generated higher frictional resistances than
      the other archwires. All brackets showed higher frictional forces as the wire
      size increased. These findings suggest that the use of an in vitro testing model
      that includes 10 brackets can give additional interesting information about the
      frictional force of the various bracket-archwires combinations to the clinician
      and the research worker.

PMID- 16448255
TI  - Unilateral mandibular widening with distraction osteogenesis.
AB  - Mandibular widening with distraction osteogenesis (DO) has been shown to be an
      acceptable and stable treatment modality. Mandibular widening with DO is useful
      in relieving crowding and for restoring a rotated mandibular arch segment to its
      original condition. This is especially true when a patient has a unilateral
      medial displacement of the proximal segment of the mandible or a unilateral
      Brodie bite. This case report shows the application of mandibular widening with
      DO for skeletal reconstruction and prosthodontic preparation in a patient with
      unilateral medial displacement of the proximal segment of the mandible. The
      design of the osteotomy line and the placement of the distractor must be taken
      into consideration in a detailed procedure for unilateral mandibular widening of
      the mandible.

PMID- 16448254
TI  - Long-term skeletal changes with rapid maxillary expansion: a systematic review.
AB  - The objective was to evaluate long-term transverse, anteroposterior and vertical
      skeletal changes after rapid maxillary expansion (RME). The data were clinical
      trials that assessed skeletal changes through cephalometric analysis. No surgical
      or other simultaneous treatment during the evaluation period was accepted.
      Electronic databases (PubMed, Medline, Medline In-Process & Other Non-Indexed
      Citations, Cochrane Database of Systematic Reviews, ASP Journal Club, DARE, CCTR,
      Embase, Web of Sciences and Lilacs) were searched with the help of a senior
      Health Sciences librarian. Abstracts that appeared to fulfill the initial
      selection criteria were selected by consensus. The original articles were then
      retrieved. A methodological checklist was used to evaluate the quality of the
      selected articles. Their references were also hand-searched for possible missing
      articles. Articles without an adequate control group to factor out growth changes
      were excluded. Only three articles (one measuring transverse and two
      anteroposterior and vertical changes) measured RME stability after active
      expansion, all of them had some methodological flaws, which limit the attainable
      conclusions. An individual analysis of these articles was made. Long-term
      transverse skeletal maxillary increase is approximately 25% of the total dental
      expansion for prepubertal adolescents. Better long-term outcomes are expected in
      transverse changes because of RME in less skeletally mature patients. RME appears
      not to produce clinically significant anteroposterior or vertical changes in the
      position of the maxilla and mandible. The conclusions from this systematic review
      should be considered with caution because only a secondary level of evidence was
      found. Long-term randomized clinical trials are needed.

PMID- 16448256
TI  - An interdisciplinary approach for improved functional and esthetic results in a
      periodontally compromised adult patient.
AB  - In contemporary dental care, an increasing number of adult patients are seeking
      orthodontic treatment. In such adult patients, a combined orthodontic and other
      specialized therapy often offers the best option for achieving a predictable
      outcome to solve complex clinical problems. This case report demonstrates a
      combined therapy with orthodontic, periodontic, and implant-prosthodontic
      treatments in a 56-year six-month-old female patient with mild diastemata in the
      maxillary anterior region and a missing left maxillary second premolar caused by
      a periodontal disease with medium bone loss. The patient had improved her oral
      hygiene condition through periodontal treatment before orthodontic treatment. The
      patient was orthodontically treated with a maxillary lingual arch and a maxillary
      edgewise orthodontic appliance. Active orthodontic treatment was completed in 18
      months, and an implant-supported prosthesis was placed with a single crown in the
      region of the left maxillary second premolar. The treatment outcomes, including
      the periodontal condition and the dental implant treatment, were stable at two
      years after the active orthodontic treatment. We demonstrate that combined
      orthodontic-periodontic-implant-prosthodontic treatment can achieve an improved
      masticatory function, esthetics, occlusion, and periodontal condition.

PMID- 16448257
TI  - Lower lip sucking habit treated with a lip bumper appliance.
AB  - The patient was an 11-year-old girl with a lower lip sucking habit with increased
      overjet, maxillary generalized spacing, and mandibular incisor irregularity.
      Hyperactivity of the mentalis muscle and deepening of the labiomental sulcus
      because of the abnormal sucking habit was observed. Orthodontic treatment was
      started with a lip bumper appliance to break the lower lip sucking habit and
      continued with fixed orthodontic mechanotherapy. The lip bumper appliance therapy
      resulted in the elimination of the lower lip sucking habit, musculus mentalis
      hyperactivity, and labiomental strain in addition to a gain in arch length,
      improvement of the lower incisor inclinations, and overjet reduction.

PMID- 16448258
TI  - Orthodontic treatment of a patient with an impacted maxillary second premolar and
      odontogenic keratocyst in the maxillary sinus.
AB  - An eight-year-, four-month-old girl was brought to the orthodontic clinic of
      Okayama University Medical and Dental Hospital. The patient had an impacted upper
      left second premolar because of an odontogenic keratocyst and showed a skeletal
      Class II jaw base relationship. At the age of six years four months,
      marsupialization of a cyst was performed at the Okayama University Medical and
      Dental Hospital because the patient had shown a swelling of the left cheek
      because of the cyst. The upper left second premolar was located in the roof of
      the maxillary sinus. The cyst was histopathologically diagnosed as an odontogenic
      keratocyst. At the age of nine years 10 months and after regaining the space for
      eruption of the premolar, the impacted premolar erupted without traction. At the
      age of 12 years five months, edgewise treatment was initiated, which continued
      for three years. After removing the edgewise appliance, an optimum occlusion was
      achieved. The occlusion was maintained without recurrence of the keratocyst after
      a retention period of five years.

PMID- 16448261
TI  - Correlation of skeletal maturation stages determined by cervical vertebrae and
      hand-wrist evaluations.
AB  - The aim of this study was to assess the correlation between the Fishman
      maturation prediction method (FMP) and the cervical vertebral maturation (CVM)
      method for skeletal maturation stage determination. Hand-wrist and lateral
      cephalograms from 79 subjects (52 females and 27 males) were used. Hand-wrist
      radiographs were analyzed using the FMP to determine skeletal maturation level
      (advanced, average, or delayed) and stage (relative position of the individual in
      the pubertal growth curve). Cervical vertebrae (C2, C3, and C4) outlines obtained
      from lateral cephalograms were analyzed using the CVM to determine skeletal
      maturation stage. Intraexaminer reliability (Intraclass correlation coefficient
      [ICC]) for both methods was calculated from 10 triplicate hand-wrist and lateral
      cephalograms from the same patients. An ICC coefficient of 0.985 for FMP and an
      ICC of 0.889 for CVM were obtained. A Spearman correlation value of 0.72 (P <
      .001) was found between the skeletal maturation stages of both methods. When the
      sample was subgrouped according to skeletal maturation level, the following
      correlation values were found: for early mature adolescents 0.73, for average
      mature adolescents 0.70, and for late mature adolescents 0.87. All these
      correlation values were statistically different from zero (P < .024). Correlation
      values between both skeletal maturation methods were moderately high. This may be
      high enough to use either of the methods indistinctively for research purposes
      but not for the assessment of individual patients. Skeletal level influences the
      correlation values and, therefore, it should be considered whenever possible.

PMID- 16448262
TI  - Changes in arch width. A 20-year longitudinal study of orthodontic treatment.
AB  - The changes in the dental arch dimensions that occur as a result of growth and
      treatment are of interest to the orthodontist and require careful consideration
      during treatment planning. A greater understanding of these changes could
      influence the patient's expectations from treatment as well as the formulation of
      the treatment and retention plans by the clinician. A retrospective study of the
      maxillary and mandibular canine and molar arch width changes in 60 patients over
      20 years was carried out. Approximately half were treated orthodontically, and
      measurements were made on dental casts taken at four time points during the
      study: 1981, 1985, 1989, and 2001. Between baseline and final follow-up, the
      treated group demonstrated a statistically significant increase in maxillary
      intercanine arch width and statistically significant decreases in maxillary
      intermolar and mandibular intercanine and intermolar widths. No significant
      changes were observed for the untreated group. When comparing the orthodontically
      treated group with the untreated group, there was a significantly greater
      increase in maxillary intercanine width and a significantly greater reduction in
      mandibular intercanine width in the treated group over the duration of the study.
      No significant difference was observed between treated and untreated groups for
      maxillary and mandibular intermolar width changes. Sex had no statistically
      significant effect on these treatment differences. Type of orthodontic treatment
      had no effect on arch width changes within the treated group; however, the effect
      of tooth extraction needs further investigation.

PMID- 16448263
TI  - A new, accurate and fast digital method to predict unerupted tooth size.
AB  - The sum of the lower incisor tooth width has been proposed as the best predictor
      for calculating unerupted canine and premolar mesiodistal tooth sizes. The aims
      of this study were to develop a new, fast, and accurate computerized method to
      predict unerupted mesiodistal tooth sizes and to determine which reference tooth
      or combination of reference teeth was the best predictor for canines and
      premolars in a Spanish sample. The dental casts of 100 Spanish adolescents with
      permanent dentition were measured to the nearest 0.05 mm with a two-dimensional
      computerized system. The goal was to predict unerupted canine and premolar
      mesiodistal tooth sizes using the sizes of the upper central incisor, upper and
      lower first molar, or a combination of these as a reference and using a specific
      mesiodistal tooth-size table. The results showed that the Digital Method proposed
      was very accurate in predicting unerupted canine and premolar tooth size. The
      combination of the sums of the permanent upper central incisor and the lower
      first molar was the best predictor for canines and premolars in this sample.
      Upper arch teeth were better predicted than lower arch teeth. The upper lateral
      incisor provided the worst predictions.

PMID- 16448265
TI  - Intermaxillary Bolton tooth size discrepancies among different malocclusion
      groups.
AB  - The orthodontic "finishing" phase is recognized for the many details necessary to
      accomplish an excellent result. A high percentage of finishing-phase difficulties
      arise because of tooth size imbalances that could have been discovered and
      considered during the initial diagnosis and treatment planning. The aim of our
      study was to determine whether there is a prevalent tendency for intermaxillary
      tooth size discrepancies among different malocclusion groups. This study involved
      60 subjects who served as the normal occlusion group and 300 patients divided
      into five malocclusion groups (ie, Class I, Class II, Class II division 1, Class
      II division 2, and Class III). Tooth size measurements were performed on the
      models of the normal occlusion group and the pretreatment models of the patients.
      The tooth size ratios and the one-way analysis of variance test showed no sexual
      dimorphism for these ratios in each of five groups, so the sexes were combined
      for each group. Then, these ratios were compared among different malocclusion
      groups. The results showed no significant difference between subcategories of
      malocclusion, so these groups were combined as Class I, Class II, and Class III.
      No significant difference was found for all the ratios between the groups.

PMID- 16448264
TI  - Dental morphology and crowding. A multivariate approach.
AB  - The objective of this study was to compare, combined and individually, the
      mesiodistal (MD) and buccolingual (BL) tooth sizes as well as their respective
      crown proportions in the permanent dentition in dental arches with moderate,
      mild, and no crowding. Dental casts from two-hundred 12 to 16-year-old school
      children from a typical high school from Lima, Peru, were used. The MD and BL
      tooth sizes of all permanent teeth except second and third molars were measured,
      and their crown proportion (MD/BL ratio) was estimated. Each dental arch was
      classified as presenting moderate (-5.1 mm or more of discrepancy), mild (-0.1
      and -5 mm of discrepancy), and no crowding (zero or a positive discrepancy).
      Combined and tooth-specific comparisons among the crowding groups for the tooth
      sizes as well as crown proportions were performed with a multivariate analysis of
      variance (MANOVA, using Wilks lambda). Combined MD tooth sizes and crown
      proportions differed among crowding groups. Subsequent individual comparisons
      indicated differences for MD tooth size of all upper teeth and for lower
      premolars and central incisors. Differences were also detected for crown
      proportions of the upper second premolar, canine, and both incisors; as well as
      for the lower first premolar, canine, and central incisor. No differences were
      found for the BL tooth sizes among crowding groups. MD tooth sizes and crown
      proportions from specific teeth are significantly different between dental arches
      with moderate, mild, and noncrowded arches. This study helps to understand the
      odontometric component of the dental crowding multifactorial origin.

PMID- 16448266
TI  - Effects of lower primary canine extraction on the mandibular dentition.
AB  - It has been reported that extraction of primary canines causes a slight mesial
      drift of the buccal segments, lingual positioning of the incisors, a decrease in
      arch length, deepening of the bite, and a slight overall crowding in the arch.
      The aim of this study was to investigate the effects of early mandibular primary
      canine extraction on permanent incisor and first molar positions, dental and
      alveolar arch widths, and arch length. Thirty-two patients in the early mixed
      dentition stage were evaluated. The treatment group (TG) included 16 patients (11
      girls, five boys) who had more than 1.6 mm of crowding. Mandibular primary
      canines were extracted bilaterally in these patients. Another 16 patients (11
      girls, five boys) who had less than 1.6 mm of crowding served as controls (CG).
      Mandibular dental casts and lateral cephalograms of the patients were obtained at
      the start (T0) and at the recall (T1) period of the trial. At the end of the one
      year observation period after removal of lower primary canines, the lower
      incisors retruded more in the TG as compared with the CG. However, changes in
      arch length, arch width, and alveolar width were similar between the groups.

PMID- 16448267
TI  - Long-term stability of lip bumper therapy followed by fixed appliances.
AB  - Lip bumper treatment has been shown to successfully increase arch width, procline
      the incisors, and distalize molars. However, few studies have been performed
      showing the long-term stability of lip bumper treatment. In this study,
      mandibular casts taken by a single practitioner from 51 patients treated with lip
      bumpers without rapid palatal expansion were analyzed at pretreatment, post-lip
      bumper treatment, posttreatment, and long-term out of treatment. Measurements of
      arch width, arch depth, arch length, and anterior crowding were made. During
      treatment, there was a mean decrease in irregularity of 3.73 mm, with a
      posttreatment increase of 0.76 mm, for a net decrease of 2.97 mm. Despite
      posttreatment decreases, significant gains in arch width were maintained for
      extended periods of time. The intercanine width had a net increase of 1.78 mm
      (19% relapse), first premolars 3.39 mm (26% relapse), second premolars 2.58 mm
      (34% relapse), and first molars 2.17 mm (20% relapse). Lip bumper treatment along
      with fixed appliances is an effective means to obtain long-term increases in arch
      width and decreases in the irregularity index.

PMID- 16448268
TI  - How a computerized tomography examination changed the treatment plans of 80
      children with retained and ectopically positioned maxillary canines.
AB  - The purpose of this study was to analyze treatment outcome and treatment planning
      before and after a computerized tomography (CT) investigation of children with
      retained and ectopically positioned maxillary canines. Intraoral and panoramic
      radiographs, computerized tomographs, and, in some cases, lateral head films were
      taken of 80 children with 113 retained maxillary canines. The incisor roots of 39
      of the 80 children had some measure of resorption. Forty-two children with
      retained maxillary canines also had a space deficiency. Diagnosis and a treatment
      plan were originally based on extraoral and intraoral photos, study models, the
      anamnesis, the status on the patient's charts, conventional radiography, and, if
      available, lateral head films. Approximately one year later, the same examiner
      drew up a new treatment plan based on the same records but with a supplemental CT
      examination. The treatment plans of 35 (43.7%) of the 80 children were modified
      to reflect this new information. Of those patients with root resorption on the
      incisors adjacent to retained canines, more than half (53.8%) of the treatment
      plans were altered. Without the CT investigation, 11 children would not have been
      treated for resorption that had exposed the pulp of an incisor root and 13 who
      had no root resorption on their incisors would have had one or both lateral
      incisors extracted. The treatment plans of the latter were changed to
      nonextraction or extraction of premolars. A CT investigation is an important
      source of information for treatment planning for children with retained or
      ectopically erupting maxillary canines.

PMID- 16448269
TI  - Vertical changes in class II division 1 malocclusion after premolar extractions.
AB  - The purpose of this study was to compare changes in the facial vertical dimension
      in patients with Class II division 1 malocclusion after the extraction of either
      mandibular first premolars or mandibular second premolars. The records of two
      groups of patients were used: one group was treated with extraction of mandibular
      first premolars (age: 13.2 +/- 1.5 years) and the other group with extraction of
      mandibular second premolars (age: 13.4 +/- 1.4 years). Each group consisted of 26
      subjects (16 boys and 10 girls). Maxillary first premolars were extracted in both
      groups. The two groups were matched by sex, age (within six months), and facial
      divergence measured by maxillary-mandibular plane angle (MM angle) and ratio of
      posterior facial height to the total anterior facial height. Student's t-test was
      used to compare the two groups. Significance was predetermined at P < .05. Second
      premolar extraction was associated with more forward movement of the mandibular
      molars, but there was no significant difference in vertical facial growth between
      the two groups. In both groups, there was no significant change in the mandibular
      plane angle and the MM angle. The results of this study do not support the
      hypothesis that mandibular premolar extraction is associated with mandibular
      overclosure or reduction in the vertical dimension, or both, in subjects with
      Class II division 1 malocclusion.

PMID- 16448270
TI  - Soft tissue changes after upper premolar extraction in Class II camouflage
      therapy.
AB  - The long-term effect on the facial profile has led many orthodontists to attempt
      Class II division I camouflage treatment without extraction. Practitioners may
      cite "dishing in the face" as a reason not to extract. Previous investigations
      have evaluated the soft tissue response after maxillary incisor retraction, but
      few have evaluated the effect of maximum retraction in skeletal mandibular
      deficient Class II patients with essentially no crowding. Twenty-seven Class II
      division I Caucasian patients with a mean of 8.62 mm of overjet, little to no
      arch length deficiency, and maximum anchorage requirements were treated with
      extraction of only maxillary first premolars. Pre- and posttreatment lateral
      cephalograms were taken. Using several skeletal and soft tissue cephalometric
      measures, the treatment changes were assessed. The mean maxillary incisor
      retraction was 5.27 mm, the mean maxillary lip retraction was 2.03 mm, and the
      mean mandibular lip retraction was 1.23 mm. All the patients finished with good
      overall facial harmony and balance. The maxillary first premolar extraction for
      orthodontic camouflage may be a viable treatment option, especially if the
      patient has full upper lips and only a relative mandibular deficiency.

PMID- 16448271
TI  - Rapid maxillary expansion and surgically assisted rapid maxillary expansion
      effects on nasal volume.
AB  - The purpose of this study was to compare the effects of rapid maxillary expansion
      (RME) and surgically assisted rapid maxillary expansion (SARME) on nasal volume
      using acoustic rhinometric methods. Two groups of subjects were used in the
      study. Group 1 consisted of 10 subjects (mean age 12.30 +/- 0.82 years) who were
      treated with RME, and group 2 consisted of 10 subjects (mean age 18.70 +/- 2.54
      years) who were treated by SARME. In both groups, all cases had a maxillary width
      deficiency with bilateral crossbites. Nasal volume records were taken by the same
      otorhinolaryngologist with an AR device. AR recordings were performed for each
      patient with and without the use of a decongestant. The first record was taken
      before expansion, and the second record was taken at the end of retention. The
      data for both groups were evaluated using Wilcoxon signed rank test and Mann
      Whitney U-test. The nasal volume showed a significant increase in both the RME
      and the SARME groups (P < .05). The measurement with the use of decongestant was
      similar to that without use of decongestant on the both groups (P < .05), but the
      different increments in nasal volume between the RME and the SARME groups were
      not statistically significant. Although the mean ages between the RME and the
      SARME groups were different, the increase in nasal volume was similar in both
      groups.

PMID- 16448272
TI  - Soft tissue to hard tissue advancement ratios for mandibular elongation using
      distraction osteogenesis in children.
AB  - Distraction osteogenesis is extensively used for the elongation of hypoplastic
      mandibles in children, yet the soft tissue profile response to this is not well
      understood. The pre- and posttreatment lateral cephalometric radiographs of 27
      pediatric patients who underwent bilateral mandibular elongation using
      distraction osteogenesis were analyzed retrospectively to correlate horizontal
      soft tissue advancement with horizontal underlying bone advancement at B point
      and pogonion. Horizontal advancement (in millimeters) of bone and overlying soft
      tissue at these points was collected from the radiographs of each patient, and
      linear regression analysis was performed to determine the relationship of hard to
      soft tissue horizontal advancement at these points. A 1:0.90 mean ratio of bone
      to soft tissue advancement was observed at B point/labiomental sulcus and at
      pogonion/soft tissue pogonion (linear regression analysis demonstrated slopes
      [beta1 values] of 0.94 and 0.92, respectively). These ratios were consistent
      throughout the sample population and are highly predictive of the soft tissue
      response that can be anticipated. Magnitude of advancement, age, and sex of the
      patient had no effect on these ratios in our population. This study assists with
      our understanding of the soft tissue response that accompanies bony elongation
      during distraction osteogenesis which will allow us to more effectively treatment
      plan the orthodontic and surgical intervention that will optimize the patients'
      functional and esthetic outcome.

PMID- 16448273
TI  - A miniature tooth-borne distractor for the alignment of ankylosed teeth.
AB  - The ankylosis of a tooth is one of the most difficult clinical problems that an
      orthodontist faces. In the literature, the treatment protocols for ankylosed
      teeth are still insufficient and questionable when considering gingival esthetics
      and conservation of bone health. The purpose of this report is to evaluate and
      discuss the effects of a newly designed miniature tooth distractor (MTD), which
      can be used with infrapositioned ankylosed teeth. Two cases with vertically
      malpositioned incisors were treated using the MTD, and this device was evaluated
      and compared with the distraction appliances used before in the literature. In
      conclusion, it was found to be efficient with its small dimensions, ease of
      application and removal, ease of activation, buccolingual control, and patient
      tolerance.

PMID- 16448274
TI  - Factors influencing applicant ranking of orthodontic programs.
AB  - Orthodontic programs spend considerable amounts of effort to attract, recruit,
      and interview the best and brightest applicants. Applicants and programs submit
      ranked preferences, and resident positions are filled by a computerized matching
      system (Match). The specific aims of this study were to determine the relative
      importance of certain factors in applicants' Match ranking of orthodontic
      programs and differences between orthodontic program directors' perceptions and
      actual factors cited by applicants influencing their ranking of orthodontic
      programs. Surveys were mailed to 55 orthodontic program directors and 478
      applicants participating in the 2002 orthodontic Match. Forty-nine program
      director (89%) and 224 applicant (47%) surveys were returned. Rankings and
      importance of factors cited by applicants in their decision-making process and
      perceptions of those factors cited by program directors were compared.
      Applicants' top three factors were: "satisfied current residents," "multiple
      techniques taught," and "good quality of clinical facility." Program directors'
      perceived top three factors were: satisfied current residents, "good program
      reputation," and "good impression of current residents at interview." Comparing
      program directors' perceptions vs applicants' factors overall, the two groups
      were statistically different (P < .0001). Factors that stood out for their
      differences included: "GRE required or emphasized" (P < .0002), multiple
      techniques taught (P < .0007), and "good location" (P < .0008). Despite these
      differences, there was generally a high level of overall agreement between
      program directors' perceptions and factors actually influencing applicants'
      ranking of orthodontic programs.

PMID- 16448276
TI  - Incidental findings of pathology and abnormality in pretreatment orthodontic
      panoramic radiographs.
AB  - Panoramic radiographs, in combination with a clinical examination, are routinely
      used as an aid to orthodontic diagnosis and treatment planning. The aim of this
      study was to evaluate the prevalence and location of incidental findings of
      pathology and abnormalities in pretreatment orthodontic panoramic radiographs. A
      total of 496 patients (232 girls and 264 boys; mean age 11.2 years, SD 2.33) were
      randomly selected from the Orthodontic Clinic at the Faculty of Odontology,
      University of Malmo, Sweden. All radiographic examinations were performed between
      1999 and 2003 at the Department of Oral Radiology, Faculty of Odontology,
      University of Malmo, Sweden. Two independent examiners analyzed the radiographs
      for abnormalities and diagnoses of pathology. However, caries and findings
      related to the orthodontic treatment plan, such as eruption disturbances and
      missing or supernumerary teeth, were not recorded. All radiographs with positive
      findings were reexamined by a third examiner, a specialist registrar in oral
      radiology. A total of 56 findings in 43 patients (8.7%) were recorded, and
      significantly more findings were detected in girls (P = .007). The most common
      findings were radiopacities (idiopathic sclerosis) in alveolar bone (n = 22),
      thickening of mucosal lining in sinus maxillaris (n = 15), and periapical
      inflammatory lesions (n = 10). The majority of the periapical lesions and
      radiopacities were found in the mandible. In most cases, the findings had no
      consequence for the orthodontic treatment plan and did not require medical or
      odontological management. However, the clinician should be aware of the potential
      to detect pathology and abnormality in pretreatment orthodontic panoramic
      radiographs.

PMID- 16448275
TI  - Canadian orthodontist Internet user profile.
AB  - An anonymous, self-administered, mail-out survey of Canadian Orthodontists was
      conducted to evaluate the characteristics of orthodontic Internet use. The
      response rate was 45.6% (304 of 667). A total of 76.6% of orthodontists reported
      having Internet access at work, and an additional 12.4% reported having Internet
      access from a different location. Statistically significant associations between
      Internet usage and office staff size (P < .001) and years of practice (P = .046)
      were observed. Offices with larger staffs had greater Internet access. Number of
      staffs and number of case starts were positively correlated (P < .001, r =
      0.498). The odds ratio for having Internet access on the basis of increased case
      starts from the less than 100 to 300-399 categories was 5.67. Although not
      statistically significant, there was a trend for greater Internet access by
      younger practitioners.

PMID- 16448277
TI  - Root resorption and immune system factors in the Japanese.
AB  - The objective of this study was to determine whether there is an association
      between excessive root resorption and immune system factors in a sample of
      Japanese orthodontic patients. The records of 60 orthodontic patients (18 males,
      age 17.7 +/- 5.7 years; 42 females, age 16.4 +/- 6.0 years) and 60 pair-matched
      controls (18 males, age 15.9 +/- 4.5 years; 42 females, age 18.5 +/- 5.2 years)
      based on age, sex, treatment duration, and the type of malocclusion were reviewed
      retrospectively. The validity of our hypothesis was tested using the logistic
      regression analysis. The pretreatment records revealed that the incidence of
      allergy and root morphology abnormality was significantly higher in the root
      resorption group (P = .030 and .001), with a mean odds ratio of 2.794 and 6.317
      and 95% confidence interval of 1.107-7.053 and 2.043-19.537, respectively. The
      incidence of asthma also tended to be higher in the root resorption group. From
      these results, we concluded that allergy, root morphology abnormality, and asthma
      may be high-risk factors for the development of excessive root resorption during
      orthodontic tooth movement in Japanese patients.

PMID- 16448278
TI  - Cephalometric norms for saudi adults living in the western region of Saudi
      Arabia.
AB  - European-American norms are still used in the orthodontic treatment of Saudi
      patients, despite the different ethnic backgrounds of Saudis. The aims of this
      study were to evaluate the cephalometric features of a Saudi population and to
      establish cephalometric norms for Saudis living in the western region of Saudi
      Arabia. Seventy lateral cephalometric radiographs of Saudis (32 females and 38
      males; aged 18-28 years) with acceptable profiles and Class I dental
      relationships were traced and analyzed. The mean value, standard deviation, and
      range of 16 angular and linear variables were calculated. The resulting norms for
      Saudis were compared with European-American norms using an independent t-test.
      Male and female groups were also compared using the t-test. Saudis tend to have
      an increased ANB angle because of retrognathic mandibles and bimaxillary
      protrusion as compared with European-Americans. Males tend to have more
      prognathic mandibles than females as indicated by the statistically significant
      increase in facial angle (P < .05) and SNB angle (P < .05). Although the anterior
      lower face height was similar in males and females, males tend to have a steeper
      mandibular plane angle when related to the anterior cranial base than females (P
      < .05). Saudis have distinct cephalometric features, which should be used as a
      reference in treating Saudi orthodontic patients.

PMID- 16448279
TI  - Self-etching primers: is prophylactic pumicing necessary? A randomized clinical
      trial.
AB  - The purpose of this clinical trial was to determine whether pumice prophylaxis is
      required before the use of a self-etching primer (SEP). A total of 30 patients
      undergoing treatment with full upper and lower fixed appliances were recruited
      into this randomized cross-mouth controlled trial. In all cases, stainless steel
      orthodontic brackets were bonded using Transbondtrade mark XT adhesive after
      pretreatment of the enamel surface using a new SEP. Diagonally opposite quadrants
      of the mouth were randomly assigned to have the enamel either pumiced or not
      pumiced before the use of a SEP. Bond failures, along with the adhesive remnant
      index (ARI) scores, were recorded at 6 and 12 months into treatment. The data
      were subsequently analyzed in terms of odds ratio and associated 95% confidence
      interval. Because of the very high bond failure rates of 55.5% for the no-pumice
      group and 33.2% for the pumice group, patient recruitment ceased at only 14
      patients. Although the bond failure rates were unacceptably high in both groups,
      pumicing was found to have a clinically and statistically significant effect on
      reducing clinical bond failure rates. The ARI scores in all cases were 0,
      indicating that no adhesive remained on the enamel surface at bond failure. The
      significance of this trial is that pumicing before the use of an SEP is to be
      recommended, although the SEP used in this study cannot be recommended for
      clinical use.

PMID- 16448280
TI  - Failure rate of self-ligating and edgewise brackets bonded with conventional acid
      etching and a self-etching primer: a prospective in vivo study.
AB  - The purpose of this study was to comparatively assess the failure rate of self
      ligating and edgewise brackets bonded with a self-etching adhesive and
      conventional phosphoric acid in patients followed for 12 months of active
      treatment. Sixty-two patients with complete permanent dentitions, similar
      treatment plans, and mechanotherapy were selected for the study. GAC Microarch
      edgewise brackets and ORMCO Damon2 brackets were bonded using a split mouth
      design, using the 3M Transbond Plus Self-etching primer (SEP) and Transbond XT
      paste; and conventional acid etching, with Orthosolo primer and Enlight paste,
      applied at an alternate sequence so that the adhesives were equally distributed
      on the maxillary and mandibular right and left quadrants. Data analysis was
      conducted with the use of logistic regression modeling. No difference in failure
      incidence was noted for either bracket-adhesive and mandibular or maxillary arch
      combinations, whereas a statistically significant difference was shown for right
      sided appliances. On the basis of the results of this study, bonding of self
      ligating brackets with SEP does not demonstrate higher probability for failure
      relative to standard bonding procedures and conventional brackets.

PMID- 16448281
TI  - Comparison of shear bond strength of two self-etch primer/adhesive systems.
AB  - Orthodontic brackets adhesive systems use three different agents, an enamel
      conditioner, a primer solution, and an adhesive resin. A unique characteristic of
      some new bonding systems is that they combine the conditioning, priming, and
      adhesive agents into a single application. The purpose of this study was to
      assess and compare the effects of using one-step and two-step self-etch
      primer/adhesive systems on the shear bond strength of orthodontic brackets. The
      brackets were bonded to extracted human molars according to one of two protocols.
      Group I (control): a two-step self-etch acidic primer/adhesive system was used,
      Transbond Plus was applied to the enamel surface as suggested by the
      manufacturer. The brackets were bonded with Transbond XT and light cured for 20
      seconds. Group II: a one-step self-etch, self-adhesive resin cement system,
      Maxcem, was applied directly to the bracket. The self-etch primer/adhesive is
      made of two components that mix automatically during application. The brackets
      were then light cured for 20 seconds. The mean shear bond strength of the two
      step acid-etch primer/adhesive was 5.9 +/- 2.7 Mpa and the mean for the one-step
      system was 3.1 +/- 1.7 MPa. The in vitro findings of this study indicated that
      the shear bond strengths (t = 3.79) of the two adhesive systems were
      significantly different (P = .001). One-step adhesive systems could potentially
      be advantageous for orthodontic purposes if their bond strength can be improved.

PMID- 16448282
TI  - Effect of a self-etching primer on shear bond strength of adhesive precoated
      brackets in vivo.
AB  - The aim of this study was to evaluate the influence of a self-etching primer
      (SEP) (Transbond Plus SEP, 3M Unitek, Monrovia, Calif) on shear bond strength of
      adhesive uncoated and precoated Victory brackets (3M Unitek). The sample group
      consisted of 23 patients, with four premolars each, equally divided in four
      different groups. Brackets were bonded in vivo by the same operator using a split
      mouth random technique: group 1, 37% phosphoric acid + primer + composite +
      conventional Victory bracket; group 2, 37% phosphoric acid + primer + precoated
      Victory bracket; group 3, SEP + composite + conventional bracket; group 4, SEP +
      precoated bracket. After 30 days, premolars were extracted for orthodontic
      reasons and a Universal Instron Machine was used to apply an occlusal shear force
      directly to the enamel-bracket interface at a speed of 0.5 mm/min. The groups
      were compared using two-way analysis of variance. Mean results and standard
      deviation for the groups were: group 1 = 11.60 +/- 2.65 Mpa, group 2 = 9.79 +/-
      2.71 Mpa, group 3 = 10.75 +/- 2.67 Mpa, and group 4 = 10.31+/- 2.70 Mpa. No
      difference was observed between the conventional etching and primer or SEP (P =
      .948). However, significant differences in bond strength were present between the
      uncoated and precoated brackets (P = .032). Considering the values required to
      withstand normal orthodontic forces (8-9 Mpa), it could be concluded that the SEP
      combined with adhesive precoated brackets showed adequate shear bond strength and
      may be suitable for clinical use.

PMID- 16448283
TI  - Scanning electron microscopy evaluation of the bonding mechanism of a self
      etching primer on enamel.
AB  - The aim of this study was to analyze the effect of a self-etching primer
      (Transbond Plus SEP, 3M Unitek, Monrovia, Calif), developed for orthodontic use,
      in the regularity and depth of adhesive infiltration in the enamel of human
      permanent teeth and to compare it with phosphoric acid using scanning electron
      microscopy (SEM). Thirty premolars were divided in two groups of 15 each: group
      1(control)-phosphoric acid + Transbond XT Primer (3M Unitek) and group 2-
      Transbond Plus SEP. Transbond XT Adhesive Paste (3M Unitek) was used in both
      groups for bracket bonding. All products were used according to the
      manufacturer's instructions. Dental fragments were decalcified, and for
      micromorphologic observation of the adhesive penetration in enamel, the resin
      replicas, remnant at the base of the brackets, were covered with a thin gold
      layer and examined by SEM. Three calibrated examiners evaluated the
      photomicrographs and gave scores from 0 = without penetration to 2 = deep
      penetration. The Mann Whitney U-test (P < .0001) showed a statistical difference
      between the two groups. The results demonstrated that the SEP was more
      conservative and produced a smaller amount of demineralization and less
      penetration of adhesive in the enamel surfaces when compared with the
      conventional phosphoric acid system.

PMID- 16448284
TI  - Use of zygomatic anchors during rapid canine distalization: a preliminary case
      report.
AB  - Rapid canine distalization is a technique involving periodontal ligament
      distraction. The primary aim of this technique is to distalize the canines
      without anchorage loss and to shorten the duration of orthodontic treatment.
      After the rapid canine distalization, the healing process of the periodontal
      ligament is similar to rapid palatal expansion and requires a consolidation
      period. The long consolidation period of the technique conflicts with the second
      aim. Skeletal anchorage systems seem to compensate for this conflict because they
      can be also used for retraction of incisors during consolidation period. This
      case report presents the orthodontic treatment of a 16-year-old female, who had a
      bimaxillary retrusion and a dental Class II division I malocclusion. Upper first
      premolars were extracted and, while the canines were being distalized rapidly by
      periodontal ligament distraction, the incisors were retracted using a zygomatic
      anchorage system. The treatment of the patient was completed in five months
      without any anchorage loss.

PMID- 16448285
TI  - Skeletal anchorage for orthodontic correction of maxillary protrusion with adult
      periodontitis.
AB  - Because the number of adult patients seeking orthodontic treatment is increasing,
      orthodontists are becoming more likely to encounter patients with adult
      periodontitis. However, it is sometimes difficult to establish anchorage because
      of poor periodontal tissues in patients with adult periodontitis. This article
      reports the successful use of skeletal anchorage to treat a maxillary protrusion
      case complicated by severe adult periodontitis. A female patient aged 50 years
      seven months showed a skeletal Class II jaw base relationship. A spacing of five
      mm in the upper anterior teeth with an overjet of 7.5 mm and overbite of four mm
      was observed. She had generalized horizontal bone loss in both arches, with
      vertical bone loss in the posterior segment. After periodontal treatment,
      miniplates were placed in the zygomatic process, and retraction and intrusion of
      the maxillary incisors were performed. After active treatment for 21 months, the
      upper incisors had been inclined 9.5 degrees lingually, intruded two mm at the
      apex, and good anterior occlusion was achieved. Acceptable occlusion and
      periodontal tissue were maintained after a retention period of two years. Our
      results suggest that skeletal anchorage is useful for retraction and intrusion of
      upper incisors in cases of maxillary protrusion with severe adult periodontitis.

PMID- 16448286
TI  - Orthopedic protraction with skeletal anchorage in a patient with maxillary
      hypoplasia and hypodontia.
AB  - Multipurpose titanium miniplates were placed on the lateral nasal wall of the
      maxilla as anchorage for face mask protraction in an 11-year-old girl presenting
      with severe maxillary hypoplasia and hypodontia. Applying orthopedic forces
      directly to the maxilla resulted in an eight mm maxillary advancement.
      Intraosseous titanium screws were also placed on the palatal bone, near the
      alveolar crests, to provide anchorage for the expansion appliance. The maxilla
      was expanded from the median palatal suture, and seven mm of expansion was
      achieved across the buccal segments. No other tooth support was used for the
      expansion or the protraction of the maxilla.

PMID- 16448288
TI  - Labially impacted maxillary canines causing severe root resorption of maxillary
      central incisors.
AB  - This is a case report of a patient with bilateral labial impaction of maxillary
      canines causing pressure resorption on the lateral aspects of the maxillary
      central incisors. The orthodontic treatment plan included extraction of the
      impacted canines, positioned between the central and the lateral incisors. Six
      years after the orthodontic treatment, the affected central incisors remained
      asymptomatic.

PMID- 16448287
TI  - Simultaneous maxillary distraction osteogenesis using a twin-track distraction
      device combined with alveolar bone grafting in cleft patients: preliminary report
      of a technique.
AB  - The simultaneous use of cleft reduction and maxillary advancement by distraction
      osteogenesis has not been applied routinely because of the difficulty in three
      dimensional control and stabilization of the transported segments. This report
      describes a new approach of simultaneous bilateral alveolar cleft reduction and
      maxillary advancement by distraction osteogenesis combined with autogenous bone
      grafting. A custom-made Twin-Track device was used to allow bilateral alveolar
      cleft closure combined with simultaneous maxillary advancement, using distraction
      osteogenesis and a rigid external distraction system in a bilateral cleft lip and
      palate patient. After a maxillary Le Fort I osteotomy, autogenous iliac bone
      graft was placed in the cleft spaces before suturing. A latency period of six
      days was observed before activation. The rate of activation was one mm/d for the
      maxillary advancement and 0.5 mm/d for the segmental transport. Accordingly, the
      concave facial appearance was improved with acceptable occlusion, and complete
      bilateral cleft closure was attained. No adjustments were necessary to the vector
      of the transported segments during the activation and no complications were
      observed. The proposed Twin-Track device, based on the concept of track-guided
      bone transport, permitted three-dimensional control over the distraction
      processes allowing simultaneous cleft closure, maxillary distraction, and
      autogenous bone grafting. The combined simultaneous approach is extremely
      advantageous in correcting severe deformities, reducing the number of surgical
      interventions and, consequently, the total treatment time.

PMID- 16448289
TI  - Orthodontic treatment protocol of Ehlers-Danlos syndrome type VI.
AB  - Ehlers-Danlos syndrome (EDS) type VI is an autosomal recessive disorder of the
      connective tissue characterized by joint hypermobility, muscle hypotonia,
      scoliosis, and ocular fragility. In this case report, an EDS type VI patient with
      a skeletal and dental Class III malocclusion is presented and the clinical
      approach to his orthodontic problem is emphasized. A 17-year-old male patient
      presenting some major and minor symptoms of the syndrome was referred to our
      orthodontic department for diagnosis and treatment. The typical clinical signs
      confirmed the diagnosis of EDS type VI. He was a skeletal and dental Class III
      malocclusion patient (both mandibular protrusion and maxillary retrusion) with a
      noncontributory family history. He had severe crowding in the lower and upper
      dental arches with retruded incisors. His first treatment plan included
      orthognathic surgery, but because of the risks of bleeding and poor healing, we
      elected to treat the patient without surgery.

PMID- 16448290
TI  - Oculo-facio-cardio-dental syndrome: report of a rare case.
AB  - Oculo-facio-cardio-dental (OFCD) syndrome is an extremely rare condition with
      ocular, facial, cardiac, and dental abnormalities. It is often unrecognized by
      many medical and dental professionals. Only 17 cases have been documented to
      date. Because all reported patients have been female, it has been suggested that
      OFCD syndrome is an X-linked dominant trait. Isolation and diagnosis of this
      syndrome is hard for the medical specialists. Only unique and specific findings
      are observed in dental and skeletal structures, which can easily be diagnosed by
      an orthodontist or general dentist. Therefore, it was the aim of this study to
      present a new case of this syndrome and to evaluate it from an orthodontic
      perspective in order to call the attention of orthodontists to this rare anomaly.

PMID- 16448292
TI  - Comparative meta-analysis of behavioral interventions for insomnia and their
      efficacy in middle-aged adults and in older adults 55+ years of age.
AB  - Meta-analyses support the effectiveness of behavioral interventions for the
      treatment of insomnia, although few have systematically evaluated the relative
      efficacy of different treatment modalities or the relation of old age to sleep
      outcomes. In this meta-analysis of randomized controlled trials (k = 23),
      moderate to large effects of behavioral treatments on subjective sleep outcomes
      were found. Evaluation of the moderating effects of behavioral intervention type
      (i.e., cognitive-behavioral treatment, relaxation, behavioral only) revealed
      similar effects for the 3 treatment modalities. Both middle-aged adults and
      persons older than 55 years of age showed similar robust improvements in sleep
      quality, sleep latency, and wakening after sleep onset. A research agenda is
      recommended to examine the mechanisms of action of behavioral treatments on sleep
      with increased attention to the high prevalence of insomnia in older individuals.

PMID- 16448293
TI  - Who is a candidate for cognitive-behavioral therapy for insomnia?
AB  - Chronic insomnia impacts 1 in 10 adults and is linked to accidents, decreased
      quality of life, diminished work productivity, and increased long-term risk for
      medical and psychiatric diseases such as diabetes and depression. Recent National
      Institutes of Health consensus statements and the American Academy of Sleep
      Medicine's Practice Parameters recommend that cognitive-behavioral therapy for
      insomnia (CBT-I) be considered the 1st line treatment for chronic primary
      insomnia. Growing research also supports the extension of CBT-I for patients with
      persistent insomnia occurring within the context of medical and psychiatric
      comorbidity. In the emerging field of behavioral sleep medicine, there has yet to
      be a consensus point of view about who is an appropriate candidate for CBT-I and
      how this determination is made. This report briefly summarizes these issues,
      including a discussion of potential contraindications, and provides a schematic
      decision-to-treat algorithm.

PMID- 16448294
TI  - Perceived racism and vascular reactivity in black college women: moderating
      effects of seeking social support.
AB  - This quasi-experimental study explored the association of perceived racism and
      seeking social support to vascular reactivity in a college sample of 110 Black
      women. Perceived racism and seeking social support were assessed via self-report,
      and vascular reactivity was measured before and during a standardized speaking
      task. Hierarchical regression analyses indicated that perceived racism was
      positively related to changes in systolic blood pressure. These analyses also
      indicated that seeking social support moderated the relationship between
      perceived racism and systolic blood pressure changes. This interaction effect
      persisted after controlling for several potential confounders. Follow-up
      regression analyses showed that perceived racism was positively associated with
      reactivity among participants who were low in seeking social support. A
      significant relationship was not observed between perceived racism and systolic
      blood pressure changes among participants who were high in seeking social
      support. Perceived racism and seeking social support were not significantly
      associated with changes in diastolic blood pressure. These findings highlight the
      importance of examining psychosocial factors that may mitigate the hypothesized
      relationship between perceived racism and reactivity.

PMID- 16448295
TI  - The influence of social environment and social image on adolescent smoking.
AB  - This purpose of this article is to explore differences by gender and school grade
      in patterns of association among social influences and tobacco use. Data from the
      1999 (N = 15,038) and 2000 (N = 35,828) National Youth Tobacco Survey (American
      Legacy Foundation, 1999, 2000), a nationally representative, repeated cross
      sectional survey, were used in the analysis. The authors compared effects on
      adolescent smoking. Direct paths from social environment to current smoking
      increased from middle school to high school. Indirect paths with social image
      mediating this relationship revealed a smaller increase. The pattern was constant
      across subsamples. Social image of smokers mediated the influence of social
      environment on adolescent smoking. Social image had a greater effect on smoking
      among middle school boys and high school girls.

PMID- 16448296
TI  - Evaluation of a multicomponent appearance-based sun-protective intervention for
      young women: uncovering the mechanisms of program efficacy.
AB  - An appearance-based sun-protection intervention program was developed,
      implemented, and evaluated in a sample of 211 Caucasian women (ages 18-25)
      randomly assigned to the sun-protection program or to a stress management
      (control) program. The sun-protection program incorporated a novel construct of
      image norms of aspirational peers (i.e., female media figures, fashion models)
      approving paleness. The authors targeted these image norms as well as the
      advantages of tanning, health beliefs about photoaging and skin cancer, and self
      efficacy for sun protection. The intervention produced significant differences
      across conditions favoring sun protection on all constructs but severity of skin
      cancer and barriers to sun protection. At follow-up, treatment participants
      exceeded controls both in intention to sun protect and sun-protective behavior
      and reported lower intention to sunbathe and fewer hours of sunbathing. A
      mediational model of intervention outcomes revealed distinct mediators for sun
      protection versus sunbathing.

PMID- 16448297
TI  - Predicting posttraumatic growth in breast cancer survivors.
AB  - Wide variability exists with respect to how breast cancer survivors respond to
      common psychological and psychosocial challenges of their disease, ranging from
      posttraumatic stress disorder to posttraumatic growth. This cross-sectional study
      examined contextual, disease-related, and intraindividual predictors of
      posttraumatic growth in 224 randomly selected breast cancer survivors. A series
      of hierarchical regression analyses found that age at diagnosis, marital status,
      employment, education, perceived intensity of disease, and active coping
      accounted for 34%, 35%, and 28% of the variance in growth in relationships with
      others, new possibilities, and appreciation for life. These findings suggest that
      a more comprehensive model of growth will be helpful in understanding the various
      factors that play a role in breast cancer survivors' perception of psychological
      and psychosocial growth.

PMID- 16448298
TI  - Forty years on: teachers' assessments of children's personality traits predict
      self-reported health behaviors and outcomes at midlife.
AB  - A life span health-behavior model was investigated in this longitudinal study of
      personality influences on health. Teachers assessed 963 elementary schoolchildren
      on traits that formed scales assessing the dimensions of the five-factor (Big
      Five) model of personality. Smoking, alcohol use, body mass index (BMI), and self
      rated health were assessed 40 years later in midlife. Childhood personality
      traits were significantly associated with all 4 outcomes, and the effects were
      consistently larger for women than men. For men and women, childhood
      Conscientiousness was associated with less adult smoking and better adult self
      rated health and, for women only, with lower adult BMI. Mediation analyses
      suggested that the effects of Conscientiousness on self-rated health were
      partially mediated by smoking and BMI. These findings add to the growing evidence
      that childhood personality traits predict adult health outcomes and are discussed
      in terms of future testing of the life span health-behavior model.

PMID- 16448299
TI  - A model of stage of change to recommend colonoscopy among urban primary care
      physicians.
AB  - Theory is little used in the prediction of physician cancer screening stage of
      change. Structural equation modeling was used to evaluate the theoretical
      predictors of stage of change to recommend colonoscopy among 235 urban
      physicians. Constructs from the theory of planned behavior, social-cognitive
      theory, and the transtheoretical model were systematically tested. As predicted,
      contextual factors, such as the physicians' ages, their race-ethnicities, patient
      race-ethnicity, and office-related barriers to preventive care were associated
      with stage of change through self-efficacy, normative beliefs, and negative
      behavioral beliefs. The findings demonstrate the relevance of these models to
      studying the behavior of physicians and support the development of interventions
      that are tailored to normative beliefs and specific physician cognitions for
      colonoscopy recommendation.

PMID- 16448300
TI  - A longitudinal evaluation of a social support model of medication adherence among
      HIV-positive men and women on antiretroviral therapy.
AB  - Nonadherence in the management of chronic illness is a pervasive clinical
      challenge. Although researchers have identified multiple correlates of adherence,
      the field remains relatively atheoretical. The authors propose a cognitive
      affective model of medication adherence based on social support theory and
      research. Structural equation modeling of longitudinal survey data from 136
      mainly African American and Puerto Rican men and women with HIV/AIDS provided
      preliminary support for a modified model. Specifically, baseline data indicated
      social support was associated with less negative affect and greater spirituality,
      which, in turn, were associated with self-efficacy to adhere. Self-efficacy to
      adhere at baseline predicted self-reported adherence at 3 months, which predicted
      chart-extracted viral load at 6 months. The findings have relevance for theory
      building, intervention development, and clinical practice.

PMID- 16448301
TI  - Emotions and preventive health behavior: worry, regret, and influenza
      vaccination.
AB  - The role of worry, regret, and perceived risk in preventive health decisions was
      explored in a longitudinal questionnaire study on influenza vaccination among 428
      university employees. The study yielded 3 main findings. First, ratings of
      anticipated worry and regret were stronger predictors of vaccination than
      perceived risk and mediated the effect of risk on vaccination. Second, the
      anticipated level of emotions differed systematically from experienced emotions,
      such that vaccinated individuals anticipated more regret and less worry than they
      actually experienced. Third, anticipated and experienced emotions had
      implications for subsequent vaccination decisions. Those who did not vaccinate in
      the 1st year but had high levels of worry and regret were likely to be vaccinated
      the following year.

PMID- 16448302
TI  - Testing a self-determination theory intervention for motivating tobacco
      cessation: supporting autonomy and competence in a clinical trial.
AB  - A longitudinal randomized trial tested the self-determination theory (SDT)
      intervention and process model of health behavior change for tobacco cessation (N
      = 1006). Adult smokers were recruited for a study of smokers' health and were
      assigned to intensive treatment or community care. Participants were relatively
      poor and undereducated. Intervention patients perceived greater autonomy support
      and reported greater autonomous and competence motivations than did control
      patients. They also reported greater medication use and significantly greater
      abstinence. Structural equation modeling analyses confirmed the SDT process model
      in which perceived autonomy support led to increases in autonomous and competence
      motivations, which in turn led to greater cessation. The causal role of autonomy
      support in the internalization of autonomous motivation, perceived competence,
      and smoking cessation was supported.

PMID- 16448304
TI  - Cardiovascular reactivity to and recovery from psychological challenge as
      predictors of 3-year change in blood pressure.
AB  - The authors examined whether cardiovascular reactivity to and recovery from
      psychological challenge predict 3-year change in blood pressure (BP) among 216
      initially normotensive, community-dwelling adults. Clinic BP assessments were
      conducted at baseline and follow-up. BP and heart rate (HR) readings were
      obtained before, during, and after 5 psychological tasks at baseline. Following
      adjustment for traditional predictors of BP and lifestyle factors, poorer
      systolic BP recovery across the tasks was associated with greater 3-year
      increases in clinic systolic and diastolic BP. Both diastolic BP recovery and HR
      recovery were also related to 3-year change in clinic BP, though cardiovascular
      reactivity measures were not. These findings suggest that the duration of stress
      related cardiovascular responses may be important for predicting longitudinal
      changes in BP.

PMID- 16448303
TI  - Mastery, sense of coherence, and mortality: evidence of independent associations
      from the EPIC-Norfolk Prospective Cohort Study.
AB  - This study investigated the association between 2 distinct personal coping
      resources (mastery and sense of coherence) and all-cause, cardiovascular, and
      cancer mortality. During follow-up (up to 6 years), 994 deaths were recorded
      among 20,323 participants, ages 41 to 80 years, in the European Prospective
      Investigation into Cancer Study in the United Kingdom. A strong sense of mastery
      was associated with lower rates of mortality from all causes, cardiovascular
      disease, and cancer, after adjusting for age, sex, and prevalent chronic physical
      disease. The association with all-cause mortality was observed for both men and
      women and remained following further adjustment for cigarette smoking, social
      class, hostility, neuroticism, and extroversion. Analysis of the joint
      association between mastery and sense of coherence revealed both personal coping
      dispositions to be independently associated with lower rates of all-cause
      mortality. In addition, these data suggested that the association for mastery was
      specific to cardiovascular mortality, whereas the association for sense of
      coherence was specific to cancer mortality. These results may aid future study of
      coping resources as determinants of persistent well-being.

PMID- 16448305
TI  - "Learning to live with what you can't rise above": control beliefs, symptom
      control, and adjustment to tinnitus.
AB  - The relations between 3 types of perceived control, symptom severity, and 2
      adaptational outcomes, depressive symptoms and psychological well-being, were
      examined in a sample of 319 people with tinnitus. Consistent with previous
      studies of control and adjustment to chronic health conditions, general health
      and symptom control were associated with better psychological adjustment, and
      retrospective control was associated with worse psychological adjustment. Only
      symptom control emerged as a significant moderator in the symptom severity
      adjustment relationship, such that stronger beliefs in one's ability to control
      symptoms were most strongly associated with better adjustment among those with
      more severe tinnitus symptoms. These findings were consistent with coping
      perspectives and cognitive adaptation theory and suggest that symptom-related
      perceptions of control may be an effective coping resource to nurture in chronic
      health contexts with severe symptoms.

PMID- 16448306
TI  - The five elements and Chinese-American mortality.
AB  - D. P. Phillips, T. E. Ruth, and L. M. Wagner (1993) reported that 1969-1990
      California mortality data show that Chinese Americans are particularly vulnerable
      to diseases that Chinese astrology and traditional Chinese medicine associate
      with their birth years. For example, because fire is associated with the heart, a
      Chinese person born in a fire year (such as 1937) is more likely to die of heart
      disease than is a Chinese person born in a nonfire year. However, many diseases
      were excluded from this study, some diseases that were included have ambiguous
      links to birth years, and the statistical tests were indirect. A more complete
      statistical analysis and independent California mortality data for the years 1960
      1968 and 1991-2002 did not replicate the original results.

PMID- 16448307
TI  - Easier done than undone: asymmetry in the malleability of implicit preferences.
AB  - Dual-process models imply that automatic attitudes should be less flexible than
      their self-reported counterparts; the relevant empirical record, however, is
      mixed. To advance the debate, the authors conducted 4 experiments investigating
      how readily automatic preferences for one imagined social group over another
      could be induced or reversed. Experiments 1 and 2 revealed that automatic
      preferences, like self-reported ones, could be readily induced by both abstract
      supposition and concrete learning. In contrast, Experiments 3 and 4 revealed that
      newly formed automatic preferences, unlike self-reported ones, could not be
      readily reversed by either abstract supposition or concrete learning. Thus, the
      relative inflexibility of implicit attitudes appears to entail, not immunity to
      sophisticated cognition, nor resistance to swift formation, but insensitivity to
      modification once formed.

PMID- 16448308
TI  - Implicit ambivalence from attitude change: an exploration of the PAST model.
AB  - Traditional models of attitude change have assumed that when people appear to
      have changed their attitudes in response to new information, their old attitudes
      disappear and no longer have any impact. The present research suggests that when
      attitudes change, the old attitude can remain in memory and influence subsequent
      behavior. Four experiments are reported in which initial attitudes were created
      and then changed (or not) with new information. In each study, the authors
      demonstrate that when people undergo attitude change, their old and new attitudes
      can interact to produce evaluative responses consistent with a state of implicit
      ambivalence. In Study 1, individuals whose attitudes changed were more neutral on
      a measure of automatic evaluation. In Study 2, attitude change led people to show
      less confidence on an implicit but not an explicit measure. In Studies 3 and 4,
      people whose attitudes changed engaged in greater processing of attitude-relevant
      information than did individuals whose attitudes were not changed.

PMID- 16448309
TI  - Not all stereotyping is created equal: differential consequences of thoughtful
      versus non-thoughtful stereotyping.
AB  - Much research emphasizes heuristic use of stereotypes, though stereotypes have
      long been considered as capable of influencing more thoughtful processing of
      social information. Direct comparisons between thoughtful and non-thoughtful
      stereotyping are lacking in the literature. Recent research in attitude change
      emphasizes the different consequences of judgments arising from relatively
      thoughtful versus non-thoughtful processes. Therefore, increased thought could
      not only fail to decrease stereotyping but might also create stereotypic
      perceptions that are more likely to have lasting impact. The current studies
      demonstrate thoughtful and non-thoughtful stereotyping within the same setting.
      More thoughtful stereotyping is more resistant to future attempts at change and
      to warnings of possible bias. Implications are discussed for the typical research
      questions asked after observing stereotypic judgements.

PMID- 16448310
TI  - Skilled or unskilled, but still unaware of it: how perceptions of difficulty
      drive miscalibration in relative comparisons.
AB  - People are inaccurate judges of how their abilities compare to others'. J. Kruger
      and D. Dunning (1999, 2002) argued that unskilled performers in particular lack
      metacognitive insight about their relative performance and disproportionately
      account for better-than-average effects. The unskilled overestimate their actual
      percentile of performance, whereas skilled performers more accurately predict
      theirs. However, not all tasks show this bias. In a series of 12 tasks across 3
      studies, the authors show that on moderately difficult tasks, best and worst
      performers differ very little in accuracy, and on more difficult tasks, best
      performers are less accurate than worst performers in their judgments. This
      pattern suggests that judges at all skill levels are subject to similar degrees
      of error. The authors propose that a noise-plus-bias model of judgment is
      sufficient to explain the relation between skill level and accuracy of judgments
      of relative standing.

PMID- 16448311
TI  - The nature of adult twin relationships: an attachment-theoretical perspective.
AB  - Twin relationships have been hailed as one of the most unique and intimate kinds
      of relationships. Unfortunately, there is a paucity of empirical research that
      addresses the interpersonal nature of twin relationships. In this article, the
      authors argue that attachment theory may provide a useful framework for
      understanding the nature of twin relationships. The authors present data
      indicating that (a) twins are more likely than non-twin siblings to use their
      sibling as an attachment figure; (b) the developmental course of twin attachment
      differs from that of other attachments; and (c) certain factors, such as genetic
      relatedness, empathy, including the other in the self, and shared experiences,
      may impact the extent to which twins use one another as attachment figures.

PMID- 16448312
TI  - When fiends become friends: the need to belong and perceptions of personal and
      group discrimination.
AB  - The present article examines the role that the need to belong (NTB) plays in
      people's judgments of personal and group discrimination and in the attributions
      people make for potentially discriminatory evaluations. The authors hypothesized
      that the NTB motivates people to conclude that (a) whereas they rarely experience
      personal discrimination, (b) their fellow in-group members do experience
      discrimination. In Study 1, people high in the NTB reported experiencing lower
      than average levels of personal and higher than average levels of group
      discrimination. In Study 2, an experimental manipulation of the NTB yielded
      similar results. In Study 3, women who were motivated to be accepted by a bogus
      male participant were less likely to attribute his negative evaluations of their
      work to prejudice.

PMID- 16448313
TI  - Examining the principles in principled conservatism: the role of responsibility
      stereotypes as cues for deservingness in racial policy decisions.
AB  - Why do educated conservatives oppose affirmative action? Those in the "principled
      conservatism" camp say opposition is based on principled judgments of fairness
      about the policies. Others, however, argue that opposition is based on racism.
      The present article offers an alternative perspective that may reconcile these
      contradictory points of view. In 2 studies, the authors show 2 major findings:
      (a) that conservatives oppose affirmative action more for Blacks than for other
      groups, in this case women, and (b) that the relationship between conservatism
      and affirmative action attitudes is mediated best by group-based stereotypes that
      offer deservingness information and not by other potential mediators like old
      fashioned racism or the perceived threat that affirmative action poses to
      oneself. The authors conclude that educated conservatives are indeed principled
      in their opposition to affirmative action, but those principles are group based
      not policy based.

PMID- 16448314
TI  - The siren's call: terror management and the threat of men's sexual attraction to
      women.
AB  - Why do sexually appealing women often attract derogation and aggression?
      According to terror management theory, women's sexual allure threatens to
      increase men's awareness of their corporeality and thus mortality. Accordingly,
      in Study 1 a subliminal mortality prime decreased men's but not women's
      attractiveness ratings of alluring women. In Study 2, mortality salience (MS) led
      men to downplay their sexual intent toward a sexy woman. In Study 3, MS decreased
      men's interest in a seductive but not a wholesome woman. In Study 4, MS decreased
      men's but not women's attraction to a sexy opposite-sex target. In Study 5, MS
      and a corporeal lust prime increased men's tolerance of aggression toward women.
      Discussion focuses on mortality concerns and male sexual ambivalence.

PMID- 16448315
TI  - Parental discipline and affection and children's prosocial behavior: genetic and
      environmental links.
AB  - The authors investigated genetic and environmental contributions to the
      relationships between children's (N=9,319 twin pairs) prosocial behavior and
      parental positivity and negativity toward them. Children's prosocial behavior was
      rated by parents at ages 3, 4, and 7 and by teachers at age 7. At each age,
      parents described their feelings and discipline toward each twin. Parental
      positivity was indexed by positive feelings and positive, non-coercive
      discipline, and parental negativity was indexed by negative feelings and
      coercive, punitive discipline. Genetics and the environment both contributed to
      individual differences in prosocial behavior and in parenting. At all ages,
      parental positivity correlated positively, and parental negativity correlated
      negatively with prosocial behavior. Genetic factors largely mediated the negative
      correlation between prosocial behavior and parental negativity. Shared
      environmental effects contributed mainly to the positive relationship between
      prosocial behavior and parental positivity. This pattern was found both cross
      sectionally and longitudinally. The findings point to the importance of
      children's characteristics and of the parent-child relationship in family
      processes.

PMID- 16448316
TI  - What is the relation between cultural orientation and socially desirable
      responding?
AB  - Research suggests that collectivists are more likely to engage in deception and
      socially desirable responding to maintain good relationships with others. In
      contrast, individualists are portrayed as candid and sincere because
      individualism encourages people to "be yourself." The authors propose that people
      with both types of cultural orientations or backgrounds engage in desirable
      responding, albeit in distinct ways. In Study 1, respondents from the United
      States compared with those from Singapore, and European Americans compared with
      Asian Americans, scored higher on self-deceptive enhancement (SDE)-the tendency
      to see oneself in a positive light and to give inflated assessment of one's
      skills and abilities- but lower on impression management (IM) by misrepresenting
      their self-reported actions to appear more normatively appropriate. In Studies 2
      to 4, horizontal individualism as a cultural orientation correlated with SDE but
      not with IM, whereas horizontal collectivism correlated with IM but not with SDE.
      Further analyses examining (a) individual differences in the tendency to answer
      deceptively and (b) responses to behavioral scenarios shed additional light on
      the culturally relevant goals served by these distinct types of socially
      desirable responding.

PMID- 16448317
TI  - Positive affect and the experience of meaning in life.
AB  - Six studies examined the role of positive affect (PA) in the experience of
      meaning in life (MIL). Study 1 showed strong relations between measures of mood,
      goal appraisals, and MIL. In multivariate analyses, PA was a stronger predictor
      of MIL than goal appraisals. In Study 2, the most consistent predictor of the
      experience of meaning in a day was the PA experienced that day. Later, global MIL
      was predicted by average daily PA, rather than average daily MIL. Study 3
      demonstrated no prospective relations between measures of MIL and PA over 2
      years. In Study 4, priming positive mood concepts enhanced MIL. In Study 5,
      manipulated positive mood enhanced ratings of MIL for those who were not given an
      attributional cue for their moods. In Study 6, PA was associated with a high
      level of distinction between meaningful and meaningless activities. Results
      indicate that positive moods may predispose individuals to feel that life is
      meaningful. In addition, positive moods may increase sensitivity to the meaning
      relevance of a situation.

PMID- 16448318
TI  - Brutal neglect: Australian rural women's access to health services.
AB  - Access to health services in rural Australia has been particularly problematic
      because of the vast geographical areas and the sparse population distribution
      across the inland. The focus on health servicing has been very much on primary
      health care with most attention being giving to the distribution of doctors in
      rural Australia. This study takes a closer look at rural health servicing through
      the eyes of women in rural Australia. Drawing on a survey of 820 women, the study
      revealed that a focus on primary health care may be resulting in a lack of
      attention to women's health in areas, such as maternity models of care, domestic
      violence and mental health. The study also reveals the disquiet of Australian
      rural women at the poor state of health services.

PMID- 16448319
TI  - Blood pressure management during acute ischaemic stroke.
AB  - Control of hypertension is a well-established goal of primary stroke prevention.
      Management of blood pressure in patients during acute ischaemic stroke, however,
      is complicated by the need to maintain brain perfusion. Lowering blood pressure
      in the acute setting may avoid the deleterious effects of high blood pressure but
      may also lead to cerebral hypoperfusion and worsening of the ischaemic stroke.
      Little information is available from clinical trials concerning optimal blood
      pressure management in acute stroke. Current protocols of thrombolytic therapy
      require strict blood pressure control below certain prescribed limits; however,
      in most acute stroke patients not treated with thrombolysis, blood pressure
      reduction is not routinely recommended and guidelines for target blood pressures
      are difficult to justify. Preliminary studies, in fact, suggest that there may be
      a role for blood pressure elevation in the treatment of some patients with acute
      ischaemic stroke.

PMID- 16448320
TI  - Evolving treatment strategies for chronic refractory angina.
AB  - Chronic refractory angina is a term used to describe patients who, despite
      optimal medical therapy, have both angina and objective evidence of ischaemia. It
      is estimated that 5-15% of the 12 million patients with chronic angina in the US
      meet the criteria for having refractory angina. This review focuses on the
      following evolving pharmacological therapies for chronic refractory angina: L
      arginine, ivabradine, ranolazine, nicorandil and trimetazidine. Evolving devices
      and invasive procedures including enhanced external counterpulsation, spinal cord
      stimulation, and transmyocardial revascularisation are also briefly discussed.

PMID- 16448321
TI  - Treatment of heparin-induced thrombocytopenia in cardiovascular patients.
AB  - Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome
      associated with heparin exposure, a falling platelet count and a high risk of
      thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use
      of heparin in this population. Should HIT be suspected, heparin must be avoided
      in most situations, and anticoagulation with an alternative anticoagulant should
      be instituted. Preferred agents include the direct thrombin inhibitors argatroban
      and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors)
      can be used in some situations. The indirect thrombin inhibitors, danaparoid and
      fondaparinux, can also be considered at times. These agents and their use in
      cardiac patients, including patients with acute coronary syndrome, percutaneous
      coronary interventions, acute ST elevation myocardial infarction or cardiac
      surgery, will be reviewed.

PMID- 16448322
TI  - Role of angiotensin II receptor blockers in atherosclerotic plaque stability.
AB  - Several clinical trials have shown that agents blocking the renin-angiotensin
      system reduce the incidence of acute ischaemic events. This effect was
      independent from blood pressure reduction and was presumably related to plaque
      stabilisation. With the aim of investigating potential mechanisms underlying this
      effect, carotid plaques were analysed in a recent study from patients randomised
      to treatment with the angiotensin receptor blocker irbesartan, or the diuretic
      chlorthalidone for 4 months before carotid endarterectomy. It was found that
      irbesartan decreased inflammatory infiltration, increased collagen content and
      downregulated prostaglandin E2-dependent metalloproteases as a consequence of
      suppression of inducible COX-2/prostaglandin E synthase. This article reviews the
      results of this study and the most recent evidence that supports the possibility
      that angiotensin II receptor blockers represent a novel therapy for plaque
      stabilisation.

PMID- 16448323
TI  - Fibrinolytic treatment for acute ischaemic stroke.
AB  - Ischaemic stroke is a leading cause of death and disability in the US. At
      present, intravenous administration of tissue plasminogen activator within 3 h of
      symptom onset is the only proven effective treatment for patients with acute
      ischaemic stroke. Unfortunately, most treated patients do not make a functional
      recovery and very few patients presenting with acute stroke qualify for
      intravenous tissue plasminogen activator therapy. The focus of current research
      is to extend the therapeutic window for intervention beyond 3 h, and to improve
      the outcome of treated patients. The purpose of the present paper is to describe
      the current state of affairs for intravenous plasminogen activators, and to
      review recently published research. Agents and strategies under investigation
      include the intra-arterial delivery of plasminogen activators or antiplatelet
      agents, as well as combined intravenous/intra-arterial protocols.

PMID- 16448325
TI  - Fungal infections in bone marrow transplant recipients.
AB  - Invasive fungal infections (IFIs) can cause significant morbidity and mortality
      in patients after haematopoietic stem cell transplantation. The two most
      notorious pathogenic fungal species in this group of patients are Candida and
      Aspergillus. Risk factors for IFIs include: prolonged neutropaenia; fungal
      overgrowth and conditioning regiment-related mucositis; graft versus host
      disease; and steroid therapy. Clinical manifestations can be protean, and
      radiological changes are frequently nonspecific. Diagnostic methods include
      culture- and nonculture-based techniques. Some experts recommend IFI prophylaxis
      in the high-risk groups, such as patients with severe graft versus host disease
      who require prolonged immunosuppressive therapy or patients with a previous
      history of aspergillosis. Treatment options include therapy with azoles,
      including the newer agent voriconazole, amphotericin and caspofungin.

PMID- 16448324
TI  - Fungal infections in solid organ transplantation.
AB  - Renal, liver, heart and lung transplantation are now considered to be the
      standard therapeutic interventions in patients with end-stage organ failure.
      Infectious complications following transplantation are relatively common due to
      the transplant recipients overall immunosuppressed status. The incidence of
      invasive mycoses following solid organ transplant ranges from 5 to 42% depending
      on the organ transplanted. These mycoses are associated with high overall
      mortality rates. Candida and Aspergillus spp. produce most of these infections.
      This article will review the risk factors, clinical presentation and treatment of
      invasive fungal infections in solid organ transplant patients, and evaluate the
      role of prophylactic therapy in this group of patients.

PMID- 16448326
TI  - Novel therapeutic approaches to the treatment of Wilson's disease.
AB  - The treatment of Wilson's disease has changed considerably in recent times, from
      the use of penicillamine (Cuprimine, Merck) for all stages and types of disease,
      to the use of three other anticopper drugs at appropriate times for appropriate
      patients. Each type and stage of the disease can be considered as a therapeutic
      target, for which specialised therapy is appropriate. This paper systematically
      reviews the various types and stages of Wilson's disease presentation, and
      provides opinion on the appropriate therapy for each. For patients presenting
      with neurological disease, the use of tetrathiomolybdate is optimum; for patients
      presenting with mild-to-moderate hepatic failure, a combination of trientine
      (Syprine, Merck) and zinc is recommended, whereas liver transplantation is
      necessary for those with severe failure; zinc therapy alone or trientine alone as
      second choice is recommended for patients presenting with hepatitis or cirrhosis
      without liver failure, for maintenance therapy, for treatment of presymptomatic
      patients and for treatment of paediatric and pregnant patients.

PMID- 16448327
TI  - Insulin detemir: from concept to clinical experience.
AB  - Insulin detemir (Levemir, Novo Nordisk) is a novel, biologically engineered
      analogue of human insulin that has been successfully developed for clinical use
      in diabetes as a basal insulin. Its unique mechanism of prolongation of action,
      achieved through acylation to give reversible albumin binding and additional self
      association, goes some way to addressing one of the fundamental limitations of
      previously available, subcutaneously administered basal insulins, a high level of
      within-person variability in time-action profile from one injection to another.
      The pharmacological profile of insulin detemir, characterised in a series of
      studies, suggested it had the potential to offer efficacy and tolerability
      advantages in the clinical setting. Such advantages, in comparison to NPH
      (neutral protamine Hagedorn) insulin, have subsequently been illustrated in
      trials. Despite glucose control targets that are identical to comparators,
      insulin detemir achieved levels of glycaemic control that, overall, were at least
      as good as NPH insulin in the Phase III development programme, with lower
      variability being a consistent finding. This was associated with consistent risk
      reductions in nocturnal hypoglycaemic events, which are closely linked with the
      basal component of insulin therapy. Another consistent finding has been a
      significantly reduced propensity for weight gain. An all-analogue regimen
      combining insulin detemir with the rapid-acting insulin aspart illustrated the
      potential benefits achievable when insulins that are designed to achieve defined
      pharmacokinetic profiles are employed clinically; blood glucose control,
      including hypoglycaemia, was significantly superior to a human insulin-based
      mealtime plus basal regimen. Insulin detemir is, therefore, a valuable addition
      to the range of exogenous insulins, as it should enable treatment regimens to be
      constructed that offer good outcomes of efficacy and tolerability.

PMID- 16448328
TI  - Eszopiclone for the treatment of insomnia.
AB  - Eszopiclone, a single-isomer, non-benzodiazepine hypnotic agent, is approved for
      use in the US for the treatment of insomnia for patients who have difficulty
      falling asleep (sleep latency) as well as for those who have difficulty staying
      asleep (sleep maintenance). Efficacy in sleep maintenance has not been
      consistently demonstrated with previous hypnotics, and long-term efficacy and
      safety data are lacking for these agents. In clinical trials, eszopiclone 3 mg
      significantly improved objective and subjective sleep measures in transient and
      chronic insomnia in adults. Nightly treatment with eszopiclone 1 mg effectively
      induced sleep in elderly patients and the 2-mg dose effectively induced and
      maintained sleep. The ability of eszopiclone 2 mg to significantly improve next
      day functioning and daytime alertness (as demonstrated by a reduction in the
      number and duration of naps) in the elderly is an important finding in clinical
      trials, and is unique to the class of hypnotic agents for the treatment of
      insomnia. Eszopiclone was well tolerated in clinical trials < or = 12 months
      duration, with no clinically significant evidence of pharmacological tolerance,
      rebound insomnia or dependence. The most frequently reported adverse event was
      unpleasant taste. Eszopiclone is the only non-benzodiazepine sedative-hypnotic
      (in the Schedule IV class under the Controlled Substances Act) to be evaluated as
      a long-term treatment for chronic insomnia.

PMID- 16448329
TI  - A catalogue of the effector secretome of plant pathogenic oomycetes.
AB  - The oomycetes form a phylogenetically distinct group of eukaryotic microorganisms
      that includes some of the most notorious pathogens of plants. Oomycetes
      accomplish parasitic colonization of plants by modulating host cell defenses
      through an array of disease effector proteins. The biology of effectors is poorly
      understood but tremendous progress has been made in recent years. This review
      classifies and catalogues the effector secretome of oomycetes. Two classes of
      effectors target distinct sites in the host plant: Apoplastic effectors are
      secreted into the plant extracellular space, and cytoplasmic effectors are
      translocated inside the plant cell, where they target different subcellular
      compartments. Considering that five species are undergoing genome sequencing and
      annotation, we are rapidly moving toward genome-wide catalogues of oomycete
      effectors. Already, it is evident that the effector secretome of pathogenic
      oomycetes is more complex than expected, with perhaps several hundred proteins
      dedicated to manipulating host cell structure and function.

PMID- 16448339
TI  - Factors affecting change in private psychotherapy patients of senior
      psychoanalysts: an effectiveness study.
AB  - Each of 51 experienced psychiatrist/psychoanalysts was queried about the clinical
      characteristics of every private psychotherapy patient presently in treatment:
      551 patients were included in the study; 88% of patients had an Axis I disorder,
      59% had Axis I and Axis II disorders concurrently, and 11% Axis II only. Of these
      patients, 44% had been prescribed psychotropic medication on a daily basis for at
      least 2 weeks during the present treatment. Patients treated for the longest time
      (5 years or more) were the most seriously psychiatrically disturbed. Patients
      improved with psychotherapy, and the improvement was related to the duration of
      treatment. The combined impact of diagnosis status, treatment duration, and
      treatment modalities provided a consistent pattern of treatment effectiveness.

PMID- 16448340
TI  - The dog's role in the analyst's consulting room.
AB  - Joe, a Labrador retriever, has accompanied an analyst in the consulting room
      since the dog was age three. Patients uniformly find him soothing and reassuring.
      In this capacity, he facilitates the therapeutic alliance and the holding
      environment. In addition, he often functions as a transitional object and
      transference displacement. Patients frequently use him as an introject for
      certain qualities they desire, such as security, strength, and confidence.
      Sometimes he promotes enactments between the patient and the analyst. At other
      times, he functions as a countertransference displacement for the analyst. On
      occasion, he is incorporated into the patient's defensive maneuvers and
      resistance. In each of these roles, he facilitates key elements of the
      therapeutic process, including exploration, understanding, interpretation, and
      working-through. Perhaps his most important role is that of a nonjudgmental,
      supportive, loyal cotherapist. Case illustrations highlight Joe's various
      functions in the analyst's consulting room.

PMID- 16448341
TI  - Integrated medical-psychiatric care of a dying borderline patient: a case of
      dynamically informed "practical psychotherapy".
AB  - Combined training in family practice and psychiatry is relatively new and
      consists of equal proportions of each specialty intermixed throughout a 5-year
      period. This blending of two distinct skill sets and patient populations creates
      opportunities to provide unique patient care. An understanding of psychodynamic
      principles is vital to treating patients with comorbid medical and psychiatric
      illnesses in a primary care setting. The patient presented in this article had
      several medical and psychiatric problems and was treated by a combined family
      practice-psychiatry resident who cared for her medically and psychiatrically
      until the time of her death from cancer. Complex patients such as this defy the
      use of purely applied school-specific psychotherapies. Rather, they require the
      creative application of integrated psychotherapeutic strategies. Integrated
      approaches to psychotherapy have been increasingly advocated in recent years. In
      keeping with terminology used by Carl Jung, this approach may be thought of
      simply as practical psychotherapy.

PMID- 16448342
TI  - Toward a "new" paradigm of therapeutic action: neuro-psychoanalysis and downward
      causation.
AB  - Freud's metapsychological assumption, which split the mind from the brain, is
      increasingly recognized as limiting the growth of psychoanalysis and its
      integration with other fields, including psychiatry. The dual-aspect monist
      position, sometimes used to rationalize the mind/body split, is seen to contain a
      mereological (category) error, which can be avoided by the introduction of the
      paradigm of psychodynamic science, and by the use of a nondualistic, symbiotic
      mind/brain formulation, well justified by the study of cultural and organic
      evolution. Therapeutic action may now be seen as a special case of development
      that occurs within the interactional context of cultural evolution, personal
      history, and the genome. Human evolution is increasingly dominated by culture
      operating on the mind/brain through downward causation. This concept refers to
      the influence of higher organizational entities (e.g., mind) upon lower ones
      (e.g., brain). Although little recognized, downward causation is tacitly assumed
      in psychotherapeutic interventions, and is illustrated in recent fMRI studies.
      The clinical integration of the downward causation concept links therapeutic
      action to the power of cultural evolution, and facilitates reunion with
      traditional science.

PMID- 16448343
TI  - The meaning bearing other--a relational view of the child psychotherapeutic
      process.
AB  - With child psychotherapy as the point of departure, meaning making in therapy may
      be described in light of the patient's relationship to the psychotherapist as "a
      meaning bearing other"-that is, someone who allows the possibility of meaningful
      thoughts and feelings, either through his or her actual communicative presence or
      as an unconsciously imagined communication partner. Within the theoretical
      framework of this article, being with a meaning bearing other is regarded as a
      prerequisite for development of both immediate, playful and reflective
      understanding of needs, wishes, and affect in self and other. The term meaning
      bearing other refers to three distinct but often synchronic modes of relatedness.
      These may be seen as developmental imperatives in both parenting and
      psychotherapy. The present article is a theoretical and clinical inquiry into the
      prerequisites for change in relationally oriented psychoanalytic psychotherapy.
      The article discusses what might be seen as basic forms of relatedness and
      interaction in light of Winnicott's developmental approach, relational and neo
      Kleinian approaches within psychoanalysis, and also Heidegger and Gadamer's
      philosophy of meaning and interaction. The theoretical points of view are
      illuminated and illustrated through an excerpt from the first session from a
      twice-a-week psychotherapy with a 5-year old boy.

PMID- 16448344
TI  - A psychodynamic approach to screening for the metabolic syndrome.
AB  - This article boldly challenges the dynamic psychiatrist to engage directly and
      vigorously into a matter that many would prefer to regard somewhat passively.
      That passivity is no longer acceptable. The metabolic syndrome has become a
      central medical concern because of the epidemic of obesity. It causes
      cardiovascular disease, diabetes, some cancers, sleep apnea, sexual dysfunction,
      and infertility. Obesity leads to depression, anxiety, and osteoarthritis. Some
      atypical antipsychotic medicines contribute to the metabolic syndrome, but the
      epidemic is widespread independent of atypicals. Practical steps by psychiatrists
      to monitor metabolic parameters are not as simple as they appear to be. Yet this
      is an area of clinical practice that cannot be ignored. Psychodynamic therapists
      need to awaken to the health of patients because the metabolic syndrome is more
      life-threatening than self-mutilation and many other self-destructive behaviors.
      The article discusses countertransference and transference issues stirred up when
      physicians begin to take responsibility for the total health of their patients.
      Freud oriented us to focus on both sides of the mind body relationship. Recent
      research on obesity, hypertension, diabetes, sleep, anxiety,depression, exercise
      and dyslipidemia is reviewed from the viewpoint of how it impinges on the office
      practice of a dynamic psychiatrist.

PMID- 16448347
TI  - The contribution of Harold F. Searles to an emerging therapeutic relationship
      with a chronic schizophrenic man.
AB  - The article describes the personal experience of the author, the development of a
      nontherapeutic relationship with a deeply regressed man, inspired and developed
      side by side with the study and the knowledge of the writings of Harold F.
      Searles. At the beginning of this experience, the author had just begun his
      university education in psychology. He found inspiration and self-confidence
      reading articles Searles wrote during his time at Chestnut Lodge. The experience
      of the author, developed out of theoretical models and knowledge, demonstrates
      that it is possible to engage psychotic people without formal psychotherapeutic
      training, accepting and sharing the idiosyncratic behavior of the other in a
      spontaneous and quiet way, using intuition and empathy.

PMID- 16448346
TI  - In the footsteps of Arieti and Fromm-Reichmann: psychodynamic treatments of
      psychosis in the current era.
AB  - The contributions of Silvano Arieti to the psychodynamic treatment of
      schizophrenia were pivotal at the time he wrote and lectured, but regretfully,
      they have slipped from current attention. They bear reviewing given the current
      era of biological reductionism in the treatment of psychoses in general. To
      illustrate Arieti's approach, he is imagined as the supervisor of a patient who
      was treated by the author during her psychiatric residency. Other clinical
      examples highlight the relevance of Arieti's philosophy for current work with
      patients suffering from psychotic disorders.

PMID- 16448349
TI  - The Da Vinci code dynamically de-coded.
AB  - The novel The Da Vinci Code, by Dan Brown has been on best-seller lists for over
      two years. An examination of Brown's previous novels reveals a well-designed plot
      line shared by all four novels that not only makes them good "thrillers" but also
      creates a mythological structure to the novels that draws on common unconscious
      fantasies in the same way that fairy tales do. One aspect of this mythological
      structure is the use of evil conspiracies (and benign ones as well) for the
      protagonist to overcome. In addition, The Da Vinci Code presents a religious
      theme involving legends about Mary Magdalene. This theme touches on the role of a
      feminine aspect to divinity in allowing for an erotic connection with the divine.

PMID- 16448350
TI  - Comment on: Chessick, Richard. Dante's Divine Comedy revisited, 2001; followed by
      author reply.

PMID- 16448354
TI  - What is your diagnosis? Diagnosis: midsagittal nondisplaced Salter-Harris type
      III fracture of the proximal phalanx of the right hind limb.

PMID- 16448355
TI  - What is your diagnosis? Diagnosis: persistent right aortic arch.

PMID- 16448356
TI  - Screwworms.
AB  - New World and Old World screwworms pose threats to the livestock industry in the
      United States and other countries. Diligence on the part of veterinarians,
      physicians, and their respective staffs is essential to protect the livestock
      industry.

PMID- 16448357
TI  - Seroprevalence of feline leukemia virus and feline immunodeficiency virus
      infection among cats in North America and risk factors for seropositivity.
AB  - OBJECTIVE: To determine seroprevalence of FeLV and FIV infection among cats in
      North America and risk factors for seropositivity. DESIGN: Prospective cross
      sectional survey. ANIMALS: 18,038 cats tested at 345 veterinary clinics (n=9,970)
      and 145 animal shelters (8,068) between August and November 2004. PROCEDURE: Cats
      were tested with a point-of-care ELISA for FeLV antigen and FIV antibody. A
      multivariable random effects logistic regression model was used to identify risk
      factors significantly associated with seropositivity while accounting for clinic
      to-clinic (or shelter) variability. RESULTS: 409 (2.3%) cats were seropositive
      for FeLV antigen, and 446 (2.5%) cats were seropositive for FIV antibody; 58
      (0.3%) cats were seropositive for infection with both viruses. Multivariable
      analysis indicated that age, sex, health status, and cat lifestyle and source
      were significantly associated with risk of seropositivity, with adults more
      likely to be seropositive than juveniles (adjusted odds ratios [ORs], 2.5 and
      2.05 for FeLV and FIV seropositivity, respectively), sexually intact adult males
      more likely to be seropositive than sexually intact adult females (adjusted ORs,
      2.4 and 4.66), and outdoor cats that were sick at the time of testing more likely
      to be seropositive than healthy indoor cats (adjusted ORs, 8.89 and 11.3).
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that certain characteristics,
      such as age, sex, health status, and lifestyle, are associated with risk of FeLV
      and FIV seropositivity among cats in North America. However, cats in all
      categories were found to be at risk for infection, and current guidelines to test
      all cats at the time of acquisition and again during illness should be followed.

PMID- 16448359
TI  - Evaluation of risk factors for Cryptococcus gattii infection in dogs and cats.
AB  - OBJECTIVE: To determine risk factors associated with Cryptococcus gattii
      infection in dogs and cats residing on Vancouver Island in British Columbia,
      Canada. DESIGN: Matched case-control study. ANIMALS: 20 dogs and 29 cats with C
      gattii infection and matched controls. PROCEDURE: Dogs and cats with a confirmed
      or probable diagnosis of cryptococcosis resulting from infection with C gattii
      were enrolled by veterinarians, and owners completed a questionnaire designed to
      obtain information pertaining to potential risk factors for the disease. Owners
      of matched control animals were also interviewed. Odds ratios and 95% confidence
      intervals or paired t tests were calculated to determine significant
      associations. RESULTS: Animals were enrolled during 2 noncontiguous periods in
      August 2001 to February 2002 (8 dogs and 9 cats enrolled) and May to December
      2003 (12 dogs and 20 cats enrolled). Risk factors significantly associated with
      development of cryptococcosis included residing within 10 km of a logging site or
      other area of commercial soil disturbance, above-average level of activity of the
      animal, travelling of the animal on Vancouver Island, hunting by the animal, and
      owners hiking or visiting a botanic garden. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results indicated that dogs and cats that were active or that lived near a site
      of commercial environmental disturbance had a significantly increased risk of
      developing C gattii infection. Veterinarians should communicate these risks to
      owners in context because cryptococcosis was an uncommon disease in this
      population.

PMID- 16448361
TI  - Sedative effects of midazolam and xylazine with or without ketamine and
      detomidine alone following intranasal administration in Ring-necked Parakeets.
AB  - OBJECTIVE: To evaluate the effects of intranasal administration of midazolam and
      xylazine (with or without ketamine) and detomidine and their specific antagonists
      in parakeets. DESIGN: Prospective study. ANIMALS: 17 healthy adult Ring-necked
      Parakeets (Psittacula krameri) of both sexes (mean weight, 128.83+/-10.46 g
      [0.28+/-0.02 lb]). PROCEDURE: The dose of each drug or ketamine-drug combination
      administered intranasally that resulted in adequate sedation (ie, unrestrained
      dorsal recumbency maintained for >or=5 minutes) was determined; the onset of
      action, duration of dorsal recumbency, and duration of sedation associated with
      these treatments were evaluated. The efficacy of the reversal agents flumazenil,
      yohimbine, and atipamezole was also evaluated. RESULTS: In parakeets, intranasal
      administration of midazolam (7.3 mg/kg [3.32 mg/lb]) or detomidine (12 mg/kg
      [5.45 mg/lb]) caused adequate sedation within 2.7 and 3.5 minutes, respectively.
      Combinations of midazolam (3.65 mg/kg [1.66 mg/lb]) and xylazine (10 mg/kg [4.55
      mg/lb]) with ketamine (40 to 50 mg/kg [18.2 to 22.7 mg/lb]) also achieved
      adequate sedation. Compared with detomidine, duration of dorsal recumbency was
      significantly longer with midazolam. Intranasal administration of flumazenil
      (0.13 mg/kg [0.06 mg/lb]) significantly decreased midazolam-associated recumbency
      time. Compared with the xylazineketamine combination, duration of dorsal
      recumbency was longer after midazolam-ketamine administration. Intranasal
      administration of flumazenil, yohimbine, or atipamezole significantly decreased
      the duration of sedation induced by midazolam, xylazine, or detomidine,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal administration of
      sedative drugs appears to be an acceptable method of drug delivery in Ring-necked
      Parakeets. Reversal agents are also effective when administered via this route.

PMID- 16448362
TI  - Circumcaval ureter associated with an intrahepatic portosystemic shunt in a dog.
AB  - CASE DESCRIPTION: A 4-month-old Bernese Mountain Dog was examined because of
      shifting hind limb lameness and lethargy of 2 weeks' duration. CLINICAL FINDINGS:
      The lameness was attributed to hypertrophic osteodystrophy. Portosystemic
      shunting was suspected on the basis of low serum albumin concentration and high
      serum bile acids concentration, and an intrahepatic shunt was identified
      ultrasono-graphically. Celiotomy was performed, and the shunt was partially
      closed with a cellophane band. During follow-up ultrasonography 7 months later,
      dilation of the left renal pelvis and proximal portion of the left ureter was
      identified. During exploratory celiotomy, the left ureter was found to pass
      dorsal to the caudal vena cava, and circumcaval ureter was diagnosed. TREATMENT
      AND OUTCOME: The ureter was transected, repositioned ventral to the vena cava,
      and anastomosed. Follow-up ultrasonographic examinations revealed gradual
      resolution of the hydronephrosis and hydroureter. CLINICAL RELEVANCE: Findings
      suggest that circumcaval ureter should be considered in the differential
      diagnosis for hydronephrosis and hydroureter in dogs. Partial obstruction of the
      middle segment of the ureter on ultrasonograms or contrast radiographs should
      increase the index of suspicion for this condition.

PMID- 16448363
TI  - Palliative use of a stent for colonic obstruction caused by adenocarcinoma in two
      cats.
AB  - CASE DESCRIPTION-Two adult male castrated cats were evaluated because of a
      history of constipation, tenesmus, or intermittent vomiting. CLINICAL FINDINGS
      Radiography and ultrasonography revealed luminal narrowing in the colon of 1 cat
      and a colonic mass in the other. A histopathologic diagnosis of colonic
      adenocarcinoma was made in both cats. TREATMENT AND OUTCOME-Under fluoroscopic
      guidance, a self-expanding metallic stent was advanced over a wire and across the
      area of colonic stenosis and deployed. One cat had progressive weight loss but
      maintained a normal appetite, energy, and a high quality of life. Fecal
      continence was maintained, and tenesmus was rarely observed. The cat was
      euthanized because of tumor metastasis 274 days after the colonic stent was
      placed. The other cat retained fecal continence, and the owners reported
      subjective improvement in the severity of tenesmus, compared with that prior to
      stent placement. The cat was euthanized 19 days after stent placement because of
      perceived decreased quality of life. CLINICAL RELEVANCE-The use of self-expanding
      metallic stents for alleviation of colonic obstruction secondary to
      adenocarcinoma in cats appears to be effective. This technique provides a simple,
      quick, nonsurgical option for palliation in cats with advanced metastatic or
      systemic disease in which surgical resection may not be possible or warranted.

PMID- 16448365
TI  - Treatment for pancreatic abscesses via omentalization with abdominal closure
      versus open peritoneal drainage in dogs: 15 cases (1994-2004).
AB  - OBJECTIVE: To compare survival rate, duration of hospitalization, and
      complications in dogs with pancreatic abscesses treated with omentalization with
      abdominal closure versus open peritoneal drainage and evaluate a pancreatitis
      severity score for potential prognostic value. DESIGN: Retrospective case series.
      ANIMALS: 15 dogs with pancreatic abscesses. PROCEDURE: Data regarding species,
      breed, age, initial clinical signs, CBC, serum biochemical abnormalities,
      pancreatitis severity score, anatomic location of the abscess, intraoperative
      bacteriologic culture results, treatment modality, postoperative complications,
      outcome (dismissed alive from the hospital, died in the postoperative period, or
      euthanized at surgery), and duration of hospitalization were evaluated. RESULTS:
      6 dogs survived, 6 dogs died or were euthanized after surgery, and 3 were
      euthanized during surgery. Five of 8 dogs treated with omentalization and
      abdominal closure survived, and 1 of 4 dogs treated with open peritoneal drainage
      survived. In several dogs, treatment required additional surgical procedures,
      which did not appear to affect outcome. Postoperative complications were similar
      among survivors and nonsurvivors. Mean duration of hospitalization for dogs
      treated with omentalization and abdominal closure was less than that of dogs
      treated with open peritoneal drainage. Neither pancreatitis severity score nor
      any individual components of the score were associated with outcome. CONCLUSIONS
      AND CLINICAL RELEVANCE: Omentalization is a viable treatment option for
      pancreatic abscess in dogs. Furthermore, shorter hospitalization and better
      survival outcomes may make omentalization preferred over open peritoneal
      drainage.

PMID- 16448366
TI  - Extensive small bowel resection in dogs and cats: 20 cases (1998-2004).
AB  - OBJECTIVE: To determine outcome in dogs and cats that underwent extensive (ie, >
      50%) resection of the small intestine and identify factors associated with
      outcome. DESIGN: Retrospective case series. ANIMALS: 13 dogs and 7 cats.
      PROCEDURE: Medical records were reviewed, and follow-up information was obtained.
      RESULTS: In all 7 cats and in 8 of the 13 dogs, extensive intestinal resection
      was performed because of a foreign body. Mean+/-SD estimated percentage of
      intestine that was removed was 68+/-14% (range, 50% to 90%). Two dogs were
      euthanized 3 days after surgery because of dehiscence of the surgical site and
      development of septic peritonitis; 1 dog died of acute respiratory distress
      syndrome 5 days after surgery. The remaining 10 dogs and 7 cats were discharged
      from the hospital, and follow-up information was available for 15 of the 17.
      Median survival time was 828 days, and 12 of the 15 animals for which long-term
      follow-up information was available had good outcomes. However, none of the
      factors examined, including percentage of intestine resected, were significantly
      associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs and cats
      that underwent extensive resection of the small intestine had a good outcome. The
      amount of intestine resected was not associated with outcome. These data may be
      useful in providing prognostic information in cases of extensive small intestinal
      resection.

PMID- 16448367
TI  - Use of ultrasonography to diagnose large colon volvulus in horses.
AB  - OBJECTIVE: To describe the use of ultrasonography to diagnose large colon
      volvulus (LCV) in horses. DESIGN: Descriptive report. ANIMALS: 4 horses with
      clinical signs of abdominal pain. PROCEDURE: Each horse was administered
      analgesic agents for pain control and placed in stocks. Ultrasonographic
      evaluations were performed with a 3.5-MHz sector scanning transducer that was
      placed parallel to the long axis of the horse (longitudinal imaging) over an area
      of the left ventral aspect of the abdomen. The boundaries of the evaluated region
      included the ventral midline, 2 vertical lines at the level of the left 10th and
      17th intercostal spaces, and a horizontal line between the 2 vertical lines at
      the level of the costal arch of the left 10th intercostal area. RESULTS: In all
      horses, nonsacculated large colon was identified ultrasonographically in the left
      ventral portion of the abdomen; this finding was considered indicative of LCV. In
      3 horses, the LCV involved intestinal rotation of 180 degrees, whereas in 1
      horse, the LCV involved intestinal rotation of 540 degrees. As confirmed by
      surgical or postmortem findings, the degree and location of the volvulus were
      correctly estimated from ultrasonographic images. CONCLUSIONS AND CLINICAL
      RELEVANCE: In horses, this method of diagnosis of LCV appears to be of value
      regardless of the location at which the rotation of the large colon occurs.
      Ultrasonographic findings may aid in the earlier diagnosis of LCV in horses,
      especially at an early stage of the disease when other clinical signs are
      equivocal.

PMID- 16448371
TI  - Efficacy of vaccination and antimicrobial treatment to eliminate chronic
      intramammary Staphylococcus aureus infections in dairy cattle.
AB  - OBJECTIVE: To determine whether a combination of vaccination and extended
      intramammary antimicrobial treatment would eliminate chronic intramammary
      Staphylococcus aureus infections in lactating dairy cows. DESIGN: Randomized
      controlled clinical trial. ANIMALS: 50 dairy cows with chronic mastitis caused by
      S aureus. PROCEDURE: Cows were identified and paired within herd on the basis of
      days in milk, lactation number, milk production, and numbers of quarters
      infected. Treated cows (n=20) received 3 doses of a polyvalent S aureus bacterin
      on days 1, 15, and 21 of the study along with intramammary administration of
      pirlimycin in all 4 quarters once daily for 5 treatments (days 16 to 20). Control
      cows (n=23) received no treatment. Follow-up samples for bacteriologic culture
      were collected for at least 3 months after treatment to determine treatment
      success rates. RESULTS: Significantly more S aureus infections were eliminated
      from treated cows (8/20 [40%]), compared with control cows (2/23 [9%]). The
      proportion of infected quarters that yielded negative results throughout the
      follow-up period was also significantly higher in treated cows (13/28 [46%]) than
      in control cows (2/41 [5%]). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate
      that a combination of vaccination and antimicrobial treatment can be successful
      in eliminating some cases of chronic intramammary S aureus infections in dairy
      cattle. However, it is important to consider extended treatment protocols
      carefully because many cows are likely to remain infected with S aureus despite
      treatment and vaccination.

PMID- 16448372
TI  - Entrenched health care practices and complex systems.

PMID- 16448369
TI  - Evaluation of factors associated with positive IgM capture ELISA results in
      equids with clinical signs compatible with West Nile virus infection: 1,017 cases
      (2003).
AB  - OBJECTIVE: To describe the prevalence of West Nile virus (WNV) infection and
      evaluate factors associated with positive IgM capture ELISA results in equids
      with clinical signs compatible with WNV infection. DESIGN: Retrospective case
      series. SAMPLE POPULATION: Laboratory submission forms from 1,104 equids tested
      for WNV in Colorado in 2003. PROCEDURES: Submission forms accompanying samples
      submitted for detection of WNV via IgM capture ELISA were obtained from the
      Colorado state veterinarian and diagnostic laboratories performing the tests.
      Data on signalment, clinical signs, history of vaccination against WNV, and assay
      results were collected from laboratory submission forms. Equids with clinical
      signs compatible with WNV infection in which IgM capture ELISA results were
      positive were considered as case equids. RESULTS: 1,104 equids were tested for
      WNV; 1,017 (92.1%) had clinical signs compatible with WNV infection. Among equids
      with clinical signs compatible with WNV infection, the odds of testing positive
      for WNV via IgM capture ELISA were lower in males and in vaccinated equids and
      higher in equids with moderate and severe illness, compared with females,
      unvaccinated equids, and equids with mild illness. CONCLUSIONS AND CLINICAL
      RELEVANCE: Among equids with clinical signs compatible with WNV infection,
      vaccination against WNV, severity of clinical signs, duration of illness, and
      region in Colorado were associated with increased risk of having a positive IgM
      capture ELISA result.

PMID- 16448373
TI  - National case management standards in Australia--purpose, process and potential
      impact.
AB  - The use of case management has been increasing within Australia. The Case
      Management Society of Australia was established in 1996 to promote the developing
      case management profession and the viability of the service model in coordinating
      care and resources for clients with complex needs. In an effort to unify the
      debate around what is expected of a case manager, the Society has reviewed its
      interim standards of practice. This paper explains the purpose, process and
      potential impact of the National Standards of Practice for Case Management. The
      intent of this article is to describe a process that unifies a diverse range of
      professionals and non-professionals who practise under the banner of case
      management. The Standards are not described in detail in this article but are
      available at <http://www.cmsa.org.au>.

PMID- 16448374
TI  - Can job sharing work for nurse managers?
AB  - Addressing employer reluctance to employ nurse managers in a job-sharing
      capacity, the aim of this paper is to explore job sharing among nurse managers.
      The literature highlighted potential fragmentation of leadership, breakdown of
      communication and higher costs as issues, with the retention of experienced
      highly motivated managers identified as an advantage. A staff survey explored
      whether the job-sharing arrangement trialled in a day surgery setting by two
      nurse managers was successful compared with similar roles held by full-time
      managers. This paper suggests that nurse managers can successfully job share.
      Overall, this paper recommends that employers consider a job-sharing arrangement
      when they wish to retain experienced nurse managers, and highlights aspects that
      can enhance a successful outcome.

PMID- 16448375
TI  - Brain drain of doctors from southern Africa: brain gain for Australia.
AB  - "Brain drain" is the depletion or loss of intellectual and technical personnel.
      The United Nations defines it as a one-way movement of highly skilled people from
      developing to developed countries that only benefits the industrialised (host)
      world. Today, brain drain is a major problem facing less developed countries,
      while Australia and other developed countries are the beneficiaries. Brain drain
      is reported to have direct negative impact on the population's health status in
      the donor country, with associated consequences for the productivity and welfare
      of the population. This paper reports on a qualitative study to understand the
      key factors behind brain drain from the perspective of the migrating doctor, and
      to consider possible solutions. Interviews were conducted with doctors who have
      migrated to Australia from southern Africa to explore reasons for brain drain.
      Specifically, the study tests the supposition that push factors play a much
      greater role than pull factors, and identifies which push factors are most
      important. Strategies to prevent brain drain from this depleted labour region are
      considered.

PMID- 16448376
TI  - Building health informatics skills for health professionals: results from the
      Australian Health Informatics Skill Needs Survey.
AB  - OBJECTIVE: To ascertain health professionals' perceptions of health informatics
      skills required in their roles. DESIGN: A paper-based survey with a stratified
      random sample of Australian health professionals and a web-based survey open to
      all Australian health professionals were conducted. MEASUREMENT: A questionnaire
      on the health professionals' perceived degree of competency required for a total
      of 69 specific skills in five skill categories based on the International Medical
      Informatics Association's (IMIA) set of recommendations on education and IMIA's
      scientific map. RESULTS: 462 health professionals responded to the paper-based
      questionnaire, and 167 respondents to the Internet questionnaire. Internet
      respondents reported higher required degrees of competency for specific health
      informatics and information technology skills than paper respondents, while paper
      respondents valued clinical skills higher than the Internet respondents.
      CONCLUSION: Health professionals increasingly use information technology (IT),
      and some also deploy, research or develop health care IT. Consequently, they need
      to be adequately educated for their specific roles in health informatics. Our
      results inform developers of educational programs while acknowledging the
      diversity of roles in health informatics and the diversity of pathways towards a
      professional health informatics qualification.

PMID- 16448377
TI  - Mentoring for population health in general practice divisions.
AB  - This paper describes the implementation and evaluation of a three-way model of
      service development mentoring. This population health mentoring program was
      funded by the Commonwealth Department of Health and Ageing to enable staff from
      eight Divisions of General Practice in South Australia to gain a sound
      understanding of population health concepts relevant to their workplace. The
      distinguishing features of service development mentoring were that the learning
      was grounded within an individual's work setting and experience; there was an
      identified population health problem or issue confronting the Division of General
      Practice; and there was an expectation of enhanced organisational performance. A
      formal evaluation found a consensus among all learners that mentoring was a
      positive and worthwhile experience, where they had achieved what they had set out
      to do. Mentors found the model of learning agreeable and effective. Division
      executive officers recognised enhanced skills among their "learner" colleagues,
      and commented positively on the benefits to their organisations through the
      development of well researched and relevant projects, with the potential to
      improve the efficiency of their population health activities.

PMID- 16448378
TI  - Future directions for Victoria's public maternity services: is this "what women
      want"?
AB  - BACKGROUND: Several state governments are once again reviewing policies for the
      provision of maternity care. This paper presents findings from a state-wide
      Victorian survey of recent mothers conducted in 2000 regarding women's
      experiences of antenatal care. We also offer some reflections on the way in which
      results from this and earlier Victorian surveys have been used, somewhat
      selectively, to support the State Government's new framework for maternity
      services, while other issues highlighted in the survey results have been
      overlooked. DESIGN: Population-based postal survey mailed to Victorian women who
      gave birth in a 2-week period in September 1999, 5-6 months after childbirth.
      RESULTS: 42% of women attending a public hospital clinic described their
      antenatal care as "very good" compared with 73% of women attending a birth
      centre, 59% attending private practitioners for antenatal care but receiving
      public intrapartum care (combined care), 56% attending a midwives clinic, 53%
      receiving shared care and 84% of women receiving private maternity care. The
      social characteristics of women enrolling in different models of care do not
      explain these differences. Immigrant women were much less likely to be happy with
      their care in pregnancy than Australian-born women, with no improvement in
      ratings of care over more than a decade.

PMID- 16448379
TI  - Tools for priority setting: lessons from South Australia.
AB  - BACKGROUND: This paper provides an overview of the process and tools used to
      develop and implement a priority setting framework for the Clinical Senate of
      South Australia. Established as a clinical advisory group to the Minister and
      Department of Health, the Clinical Senate recognised the need for an open
      priority setting process to fairly assign planning resources to the large number
      of clinical issues that needed to be addressed. DISCUSSION: Using a workbook,
      developed from the literature and evidence related to priority setting, agreement
      was reached on the use, components and structure of the priority setting process.
      The final products included a Gap Finder Tool and a Priority Setting Framework.
      SUMMARY: This paper describes the process used to develop the priority setting
      tools. Decision makers in other organisations can use similar processes and tools
      to develop or enhance their priority Setting processes.

PMID- 16448380
TI  - Health care financing and public responses: use of private insurance in Western
      Australia during 1980-2001.
AB  - OBJECTIVES: The aim was to identify and explain trends and cut points in payment
      classification (privately insured or otherwise) for episodes of hospitalisation
      in Western Australia. METHODS: Hospital morbidity data from 1980 to 2001 were
      used to produce trend lines of the proportion of hospital separations in each
      payment category in each year in age and clinical subgroups. RESULTS: The most
      significant changes in payment classification over time were found in all groups
      between 1980 and 1984, corresponding to a period when free public hospital care
      in Australia was abolished (Sep 1981 to Feb 1984). The trend associated with this
      policy change rebounded significantly just before the introduction of Medicare in
      1984. These observations were consistent over all age groups except in the oldest
      group (70+ years). This trend was more pronounced for the surgical subgroup
      compared with other broad clinical categories. More recently, a trend towards
      increasing public episodes was reversed from 2000 following introduction of
      incentives for private health cover and sanctions against deferred uptake in
      younger people. CONCLUSION: The public appeared to adopt a short-term crisis
      reaction to major policy change but then reversed towards past patterns of
      behaviour. The implications for policy makers include the need to understand the
      underlying culture of the population; to realise that attitudes become fixed as
      people age; and to recognise the difference in the effectiveness of incentive-
      and deterrent-based policies.

PMID- 16448381
TI  - Diagnosis-based risk adjustment and Australian health system policy.
AB  - Diagnosis-based risk adjustment is increasingly seen as an important tool for
      establishing capitation payments and evaluating appropriateness and efficiency of
      services provided and has become an important area of research for many countries
      contemplating health system reform. This paper examines the application of a risk
      adjustment method, extensively validated in the United States, known as
      diagnostic cost groups (DCG), to a large Australian hospital inpatient data set.
      The data set encompassed hospital inpatient diagnoses and inpatient expenditure
      for the entire metropolitan population residing in the state of New South Wales.
      The DCG model was able to explain 34% of individual-level variation in concurrent
      expenditure and 5.2% in subsequent year expenditure, which is comparable to US
      studies using inpatient-only data. The degree of stability and internal
      consistency of the parameter estimates for both the concurrent and prospective
      models indicate the DCG methodology has face validity in its application to NSW
      health data sets. Modelling and simulations were conducted which demonstrate the
      policy applications and significance of risk adjustment model(s) in the
      Australian context. This study demonstrates the feasibility of using large
      individual-level data sets for diagnosis-based risk adjustment research in
      Australia. The results suggest that a research agenda should be established to
      broaden the options for health system reform.

PMID- 16448382
TI  - People under 60 living in aged care facilities in Victoria.
AB  - OBJECTIVE: To describe the characteristics of people under 60 years of age living
      in residential aged care in Victoria and to examine the occupational
      participation of younger residents in aged care facilities by measuring their
      social contact, participation in recreation and community access. METHODS: A
      survey was sent to the Directors of Nursing at all 803 Commonwealth Department of
      Health and Aged Care registered aged care facilities in Victoria. RESULTS: The
      survey had a 78% response rate and information was provided about the
      characteristics of 330 people under 60 years with high clinical needs residing in
      aged care facilities. This sample was extremely isolated from peers, with 44%
      receiving a visit from a friend less often than once per year. Sixteen per cent
      of residents participated in a recreation activity less than once per month and
      21% went outside less than once per month. Of the sample, 34% almost never
      participated in any community-based activities such as shopping, leisure or
      visiting friends and family. CONCLUSION: Over one third of younger people in aged
      care are effectively excluded from life in our community. Most younger residents
      are socially isolated and have limited opportunities for recreation. Placement of
      younger people in aged care facilities is inappropriate, and alternative care
      models and settings are required.

PMID- 16448383
TI  - Improving access to evidence-based acute stroke services: development and
      evaluation of a health systems model to address equity of access issues.
AB  - Level 1 evidence for management of patients with stroke in a dedicated Stroke
      Care Unit (SCU) demonstrates improved outcomes by about 20%. It has been
      estimated that 21% of Australian hospitals provide an SCU and that these SCUs are
      mainly located in either metropolitan sites and/or in hospitals with more than
      300 beds. To address equity issues related to access to SCUs, the National Stroke
      Foundation and the Australian Government undertook the National Stroke Units
      Program. One program outcome was the development of a conceptual model of acute
      stroke service delivery. The development process and initial evaluation of the
      model are described. Use of the model to increase capacity within the health care
      system to treat stroke is discussed.

PMID- 16448385
TI  - Size of myocardial infarction induced by ischaemia/reperfusion is unaltered in
      rats with metabolic syndrome.
AB  - Obesity is associated with metabolic syndrome and increased incidence of and
      mortality from myocardial infarction. The aim of the present study was to develop
      an animal model with metabolic syndrome and examine how that influences size of
      myocardial infarcts induced by occlusion and reperfusion of the left anterior
      descending coronary artery. Sprague-Dawley rats (n = 105) were fed either LF (low
      fat) or MHF (moderately high-fat) diets for 13 weeks before coronary occlusion
      for 45 min, followed by reperfusion for 60 min. Compared with LF-fed and lean MHF
      fed rats, obese MHF-fed rats developed metabolic disturbances similar to those
      seen in the metabolic syndrome, including being overweight by 24% (compared with
      lean MHF-fed rats), having 74% more visceral fat (compared with LF-fed rats), 15%
      higher blood pressure (compared with LF-fed rats), 116% higher plasma insulin
      (compared with lean MHF-fed rats), 10% higher fasting plasma glucose (compared
      with LF-fed rats), 35% higher non-fasting plasma glucose (compared with lean MHF
      fed rats), 36% higher plasma leptin (compared with lean MHF-fed rats) and a
      tendency to lower plasma adiponectin and higher plasma non-esterified fatty
      acids. Infarct size was similar in the three groups of rats (36+/-14, 42+/-18 and
      41+/-14% in obese MHF-fed, lean MHF-fed and LF-fed rats respectively). In
      conclusion, rats fed a MHF diet developed metabolic syndrome, but this did not
      influence myocardial infarct size.

PMID- 16448384
TI  - Cellular cholesterol controls TRPC3 function: evidence from a novel dominant
      negative knockdown strategy.
AB  - TRPC3 (canonical transient receptor potential protein 3) has been suggested to be
      a component of cation channel complexes that are targeted to cholesterol-rich
      lipid membrane microdomains. In the present study, we investigated the potential
      role of membrane cholesterol as a regulator of cellular TRPC3 conductances.
      Functional experiments demonstrated that cholesterol loading activates a non
      selective cation conductance and a Ca2+ entry pathway in TRPC3-overexpressing
      cells but not in wild-type HEK-293 (human embryonic kidney 293) cells. The
      cholesterol-induced membrane conductance exhibited a current-to-voltage
      relationship similar to that observed upon PLC (phospholipase C)-dependent
      activation of TRPC3 channels. Nonetheless, the cholesterol-activated conductance
      lacked negative modulation by extracellular Ca2+, a typical feature of agonist
      activated TRPC3 currents. Involvement of TRPC3 in the cholesterol-dependent
      membrane conductance was further corroborated by a novel dominant-negative
      strategy for selective blockade of TRPC3 channel activity. Expression of a TRPC3
      mutant, which contained a haemagglutinin epitope tag in the second extracellular
      loop, conferred antibody sensitivity to both the classical PLC-activated as well
      as the cholesterol-activated conductance in TRPC3-expressing cells. Moreover,
      cholesterol loading as well as PLC stimulation was found to increase surface
      expression of TRPC3. Promotion of TRPC3 membrane expression by cholesterol was
      persistent over 30 min, while PLC-mediated enhancement of plasma membrane
      expression of TRPC3 was transient in nature. We suggest the cholesterol content
      of the plasma membrane as a determinant of cellular TRPC3 activity and provide
      evidence for cholesterol dependence of TRPC3 surface expression.

PMID- 16448386
TI  - Tissue-specific expression of ferritin H regulates cellular iron homoeostasis in
      vivo.
AB  - Ferritin is a ubiquitously distributed iron-binding protein. Cell culture studies
      have demonstrated that ferritin plays a role in maintenance of iron homoeostasis
      and in the protection against cytokine- and oxidant-induced stress. To test
      whether FerH (ferritin H) can regulate tissue iron homoeostasis in vivo, we
      prepared transgenic mice that conditionally express FerH and EGFP (enhanced green
      fluorescent protein) from a bicistronic tetracycline-inducible promoter. Two
      transgenic models were explored. In the first, the FerH and EGFP transgenes were
      controlled by the tTA(CMV) (Tet-OFF) (where tTA and CMV are tet transactivator
      protein and cytomegalovirus respectively). In skeletal muscle of mice bearing the
      FerH/EGFP and tTA(CMV) transgenes, FerH expression was increased 6.0+/-1.1-fold
      (mean+/-S.D.) compared with controls. In the second model, the FerH/EGFP
      transgenes were controlled by an optimized Tet-ON transactivator, rtTA2(S)
      S2(LAP) (where rtTA is reverse tTA and LAP is liver activator protein), resulting
      in expression predominantly in the kidney and liver. In mice expressing these
      transgenes, doxycycline induced FerH in the kidney by 14.2+/-4.8-fold (mean+/
      S.D.). Notably, increases in ferritin in overexpressers versus control
      littermates were accompanied by an elevation of IRP (iron regulatory protein)
      activity of 2.3+/-0.9-fold (mean+/-S.D.), concurrent with a 4.5+/-2.1-fold
      (mean+/-S.D.) increase in transferrin receptor, indicating that overexpression of
      FerH is sufficient to elicit a phenotype of iron depletion. These results
      demonstrate that FerH not only responds to changes in tissue iron (its classic
      role), but can actively regulate overall tissue iron balance.

PMID- 16448388
TI  - Rho/ROCK-dependent pseudopodial protrusion and cellular blebbing are regulated by
      p38 MAPK in tumour cells exhibiting autocrine c-Met activation.
AB  - BACKGROUND INFORMATION: The c-Met-dependent, beta-actin-rich, blebbed pseudopodia
      of MSV-MDCK-INV (invasive Moloney-sarcoma-virus-transformed Madin-Darby canine
      kidney) cells are induced by Rho/ROCK (Rho kinase) activation, and are
      morphologically distinct from flat extended lamellipodia. RESULTS: Microtubules
      were shown to extend to these actin-rich pseudopodial domains, and microtubule
      depolymerization by nocodazole treatment resulted in progressive cellular
      blebbing, initiating in the pseudopodial domains and resulting in transient
      cellular rounding and blebbing after 30 min. The blebbing response was dependent
      on autocrine HGF (hepatocyte growth factor) activation of c-Met and prevented by
      inhibition of RhoA, ROCK and p38 MAPK (p38 mitogen-activated protein kinase), but
      not ERK (extracellular-signal-regulated kinase) or PI3K (phosphoinositide 3
      kinase). Phospho-p38 MAPK was present in pseudopodia, localizing activation of
      this signalling pathway to this protrusive membrane structure. In serum-starved
      cells, LPA (lysophosphatidic acid) activation of RhoA induced p38 MAPK-dependent
      pseudopodial protrusions, and inhibition of p38 MAPK prevented pseudopodial
      protrusion and displacement of MSV-MDCK-INV cells. MSV-MDCK-INV cells exhibited
      intermittent blebbing and rounding, which may represent an integral part of their
      motile behaviour. CONCLUSIONS: The localized activation of an autocrine HGF/c-Met
      loop regulates Rho/ROCK activation of p38 MAPK signalling to stimulate both
      membrane blebbing and pseudopod formation.

PMID- 16448387
TI  - Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome
      related organelles complex-1) as a dystrobrevin-binding protein.
AB  - Dysbindin was identified as a dystrobrevin-binding protein potentially involved
      in the pathogenesis of muscular dystrophy. Subsequently, genetic studies have
      implicated variants of the human dysbindin-encoding gene, DTNBP1, in the
      pathogeneses of Hermansky-Pudlak syndrome and schizophrenia. The protein is a
      stable component of a multisubunit complex termed BLOC-1 (biogenesis of lysosome
      related organelles complex-1). In the present study, the significance of the
      dystrobrevin-dysbindin interaction for BLOC-1 function was examined. Yeast two
      hybrid analyses, and binding assays using recombinant proteins, demonstrated
      direct interaction involving coiled-coil-forming regions in both dysbindin and
      the dystrobrevins. However, recombinant proteins bearing the coiled-coil-forming
      regions of the dystrobrevins failed to bind endogenous BLOC-1 from HeLa cells or
      mouse brain or muscle, under conditions in which they bound the Dp71 isoform of
      dystrophin. Immunoprecipitation of endogenous dysbindin from brain or muscle
      resulted in robust co-immunoprecipitation of the pallidin subunit of BLOC-1 but
      no specific co-immunoprecipitation of dystrobrevin isoforms. Within BLOC-1,
      dysbindin is engaged in interactions with three other subunits, named pallidin,
      snapin and muted. We herein provide evidence that the same 69-residue region of
      dysbindin that is sufficient for dystrobrevin binding in vitro also contains the
      binding sites for pallidin and snapin, and at least part of the muted-binding
      interface. Functional, histological and immunohistochemical analyses failed to
      detect any sign of muscle pathology in BLOC-1-deficient, homozygous pallid mice.
      Taken together, these results suggest that dysbindin assembled into BLOC-1 is not
      a physiological binding partner of the dystrobrevins, likely due to engagement of
      its dystrobrevin-binding region in interactions with other subunits.

PMID- 16448389
TI  - Effect of Ku proteins on IRES-mediated translation.
AB  - BACKGROUND INFORMATION: Ku is an abundant nuclear heterodimeric protein composed
      of 70 and 86 kDa subunits. As an activator of the catalytic subunit of DNA-PK
      (DNA-dependent protein kinase), Ku plays an important role in DNA repair and
      recombination. Ku is also involved in actions independent of DNA-PK, such as
      transcription regulation and telomere maintenance. Although Ku is localized in
      the cytoplasm under specific cellular conditions, no functions for Ku outside of
      the nucleus have as yet been reported. In addition to DNA binding, Ku binds
      specific RNA sequences with high affinity. However, no specific cellular mRNA
      targets for Ku have been identified. RESULTS: In a yeast three-hybrid system,
      Ku70 bound to an RNA bait that contained an IRES (internal ribosomal entry site)
      element. A single band with migration properties similar to those of Ku70 was
      immunoprecipitated with anti-Ku antibody, using UV cross-linked complexes formed
      by HeLa cell nuclear extracts and an IRES-containing RNA probe. IRES activity was
      reduced in Ku80(-/-) cells. Overexpression of Ku proteins stimulated IRES
      dependent translation. CONCLUSIONS: The present study suggests that Ku binds IRES
      elements within RNA molecules, and that Ku plays a role in the modulation of IRES
      mediated mRNA translation.

PMID- 16448390
TI  - Evidences of the gender-related differences in cardiac repolarization and the
      underlying mechanisms in different animal species and human.
AB  - Clinical and experimental studies have shown that gender differences exist in
      cardiac repolarization in various animal species and human, as is evidenced by
      significantly longer QT, JT intervals and action potential duration in females
      than in males due to a reduced repolarization reserve in females. The latter is
      shown by the relatively greater increase in ventricular repolarization and higher
      incidence of torsades de pointes (TdP) in preparations from females by drugs
      blocking repolarizing K(+) currents. These results can be modulated by
      gonadectomy, suggesting that gonadal steroids are important determinants of
      gender difference in repolarization. In human subjects, QT and JT intervals are
      longer in women, whereas QT dispersion and Tp-e interval (the interval from the
      peak to the end of T wave) are longer in men. At slow heart rates greater
      prolongation in QT and increase in transmural repolarization heterogeneity (i.e.
      increase in Tp-e) may predispose to TdP tachycardias in women. In healthy
      postmenopausal women, hormone replacement therapy with estrogen alone usually
      produced a prolongation of QT interval, while estrogen plus progesterone had no
      significant effects on QT interval but reduced QT dispersion. Along with these,
      there are still conflicting data reported. Further work is needed before the
      elucidation of the basis of gender differences in ventricular repolarization.

PMID- 16448391
TI  - Adenosine receptors: promising targets for the development of novel therapeutics
      and diagnostics for asthma.
AB  - Interest in the role of adenosine in asthma has escalated considerably since the
      early observation of its powerful bronchoconstrictor effects in asthmatic but not
      normal airways. A growing body of evidence has emerged in support of a
      proinflammatory and immunomodulatory role for the purine nucleoside adenosine in
      the pathogenic mechanisms of chronic inflammatory disorders of the airways such
      as asthma. The fact that adenosine enhances mast cell allergen-dependent
      activation, that elevated levels of adenosine are present in chronically inflamed
      airways, and that adenosine given by inhalation cause dose-dependent
      bronchoconstriction in subjects with asthma emphasizes the importance of
      adenosine in the initiation, persistence and progression of these common
      inflammatory disorders of the airways. These distinctive features of adenosine
      have been recently exploited in the clinical and research setting to identify
      innovative diagnostic applications for asthma. In addition, because adenosine
      exerts its multiple biological activities by interacting with four adenosine
      receptor subtypes, selective activation or blockade of these receptors may lead
      to the development of novel therapies for asthma.

PMID- 16448392
TI  - Stem cell factor expression, mast cells and inflammation in asthma.
AB  - The Kit ligand SCF or stem cell factor (SCF) is a multipotent growth factor,
      acting as an important growth factor for human mast cells. SCF induces chemotaxis
      and survival of the mast cell, as well as proliferation and differentiation of
      immature mast cells from CD34(+) progenitors. Additionally, SCF enhances antigen
      induced degranulation of human lung-derived mast cells, and induces a mast cell
      hyperplasia after subcutaneous administration. SCF expression increases in the
      airways of asthmatic patients, and this is reversed after treatment with
      glucocorticoids. A role for SCF may thus be hypothesized in diseases associated
      with a local increase in the number and/or activation of mast cells, as occurring
      in the airways in asthma. SCF will be reviewed as a potential therapeutic target
      in asthma, to control the regulation of mast cell number and activation. We here
      report the main pathways of SCF synthesis and signalling, and its potential role
      on airway function and asthma.

PMID- 16448393
TI  - Cardiovascular and metabolic effects of natriuretic peptides.
AB  - Natriuretic peptides (NP) are essential in mammals to regulate blood volume and
      pressure. The functional roles of NP are not limited to natriuresis and diuresis.
      Several peripheral and central actions of the peptides have been characterized.
      Studies on transgenic mice have revealed their key function in the regulation of
      cardiomyocyte growth. Plasma NP levels increase in patients with cardiovascular
      disorders and heart failure. They represent useful clinical markers for
      clinicians to diagnose heart diseases. The recent discovery of their potent
      lipolytic action in adipose tissue is a breakthrough in cardiovascular medicine.
      This new function of NP in the regulation of lipid metabolism offers interesting
      questions in the field of obesity, diabetes and cardiovascular diseases. This
      review will briefly describe the effects of NP on the cardiovascular system and
      lipid metabolism.

PMID- 16448394
TI  - Early pharmacological preconditioning by erythropoietin mediated by inducible NOS
      and mitochondrial ATP-dependent potassium channels in the rat heart.
AB  - Administration of recombinant human erythropoietin (rhEPO) is known to induce
      protection against cardiac ischaemia injury improving functional recovery and
      reducing apoptosis. But the underlying mechanisms are not elucidated. We
      determined the role of nitric oxide synthases (NOS) as well as ATP-dependent
      (K(ATP)) and calcium-activated (K(Ca)) potassium channels in the early
      cardioprotection induced by rhEPO. Wistar male rats were divided into two
      experimental groups treated by rhEPO (5,000 IU/kg, i.p.) or saline (control
      group). One hour later, rats were anaesthetized, hearts isolated, retrogradely
      perfused and submitted to a 30-min no-flow global ischaemia followed by 120 min
      of reperfusion sequence. Cardiac functional recovery (left ventricular developed
      pressure, LVDP) was significantly higher in the group treated by rhEPO (LVDP at
      30 min reperfusion: 71.7 +/- 2.3 mmHg) compared with the control group (57.4 +/-
      5.8 mmHg). We observed the same significant effect on its derivative (dP/dt). The
      rhEPO-induced improvement in ventricular function was abolished by perfusion
      prior to ischaemia with either N-nitro-l-arginine methyl ester (l-NAME, a
      nonspecific NOS inhibitor) or N-(3-(aminomethyl)benzyl)acetamidine (1,400W, a
      specific inducible NOS inhibitor) or 5-hydroxydecanoic acid (5HD, a mitochondrial
      K(ATP) channel blocker) but not with paxilline (a K(Ca) channel inhibitor). Thus,
      in vivo rhEPO administration provides early preconditioning against ischaemic
      injury in the isolated perfused rat heart that is dependent on iNOS and
      mitochondrial K(ATP) channels.

PMID- 16448395
TI  - Radish seed extract mediates its cardiovascular inhibitory effects via muscarinic
      receptor activation.
AB  - In this study, we describe the hypotensive, cardio-modulatory and endothelium
      dependent vasodilator actions of Raphanus sativus (radish) seed crude extract in
      an attempt to provide scientific basis for its traditional use in hypertension.
      The plant extract (Rs.Cr) was prepared in distilled water and was subjected to
      phytochemical screening using standard analytical procedures. In vivo blood
      pressure was monitored in anaesthetized normotensive rats. Isolated tissue
      preparations were suspended in tissue baths containing Kreb's solution while
      acute toxicity study was performed in mice for 24 h. Rs.Cr tested positive for
      the presence of saponins, flavonoids, tannins, phenols and alkaloids and caused a
      dose-dependent (0.1-3 mg/kg) fall in blood pressure and heart rate of rats that
      was mediated via an atropine-sensitive pathway. In isolated guinea-pig atria,
      Rs.Cr showed dose-dependent (0.03-3.0 mg/mL) inhibition of force and rate of
      contractions. In the atropine-treated tissues, the inhibitory effect was
      abolished and a cardiac stimulant effect was unmasked which was resistant to
      adrenergic and serotonergic receptor blockade. In the endothelium-intact rat
      aorta, Rs.Cr inhibited phenylephrine-induced contractions, which was blocked by
      atropine and Nomega-Nitro-L-arginine methyl ester hydrochloride while was also
      absent in the endothelium-denuded preparations. The extract was safe in mice up
      to the dose of 10 g/kg. The study shows that the cardiovascular inhibitory
      effects of the plant are mediated through activation of muscarinic receptors thus
      possibly justifying its use in hypertension.

PMID- 16448396
TI  - Anti-inflammatory effect of licofelone against various inflammatory challenges.
AB  - We investigated the pharmacological profile of licofelone [6-(4-chlorophenyl)-2,3
      dihydro-2,2-dimethyl-7-phenyl-1H-pyrrolizine-5-acetic acid] against different
      inflammogens. The anti-inflammatory and anti-hyperalgesic effect of licofelone
      (2, 30 and 100 mg/kg, p.o.) against all the challenges was statistically
      significant (P < 0.05) when compared with control and indomethacin (10 mg/kg,
      p.o.). The ED(50) value of 19.1 mg/kg (onset by 2 h, duration: short), 13.0 mg/kg
      and 16.8 mg/kg (onset by 1 h, duration: long) was observed for licofelone against
      carrageenan-, arachidonic acid- and bradykinin-induced paw oedema, respectively.
      Similarly, licofelone showed ED(50) value of 47.6 mg/kg (onset by 1 h, duration:
      long), 92.2 mg/kg (onset by 1 h, duration: medium), and 78.6 mg/kg (onset by 2 h,
      duration: medium) against carrageenan-, arachidonic acid- and bradykinin-induced
      mechanical hyperalgesia, respectively. The rank order of potency based on percent
      inhibition and percent reversal against inflammation and mechanical hyperalgesia,
      respectively, was found to be licofelone > indomethacin. Moreover, licofelone (10
      100 mg/kg, p.o.) significantly (P < 0.05) and dose-dependently prevented the
      Freund's adjuvant-induced increased vascularity in mice (vascularity index; 10
      mg/kg: 0.059 +/- 0.015; 20 mg/kg: 0.048 +/- 0.004; 30 mg/kg: 0.039 +/- 0.012; 100
      mg/kg: 0.025 +/- 0.015 vs. control: 0.0285 +/- 0.003). Furthermore, the results
      suggested that dual inhibitors of cyclooxygenase and lipoxygenase like licofelone
      provide an effective control of inflammation and hyperalgesia against acute
      inflammation/hyperalgesia in rats and mice.

PMID- 16448397
TI  - Melatonin cytotoxicity in human leukemia cells: relation with its pro-oxidant
      effect.
AB  - Melatonin has a variety of functions in human physiology and is involved in a
      number of pathological events including neoplastic processes. The tissue
      protective actions of melatonin are attributed to its antioxidant activity
      though, under certain conditions, melatonin might also exert oxidant effects,
      particularly in cancer cells. This study evaluated the effects of 10(-5) and 10(
      3) m concentrations of melatonin on human leukemia cells. Moderate cytotoxic
      effects of melatonin at 10(-3) m concentrations were observed in CMK, Jurkat and
      MOLT-4 cells which was associated with significant reactive oxygen species (ROS)
      generation. Melatonin treatment was not associated with significant cytotoxicity
      in HL-60 cells, although the generation of ROS was significantly increased. K562
      and Daudi cells did not appear to be effected by melatonin treatment. Cellular
      membrane lipid peroxidation was not influenced by melatonin with the exception of
      CMK cells. Cell cycle kinetics were not affected in melatonin-treated samples,
      again with the exception of CMK cells which showed increased apoptosis.
      Melatonin, therefore, induces the production of ROS that may be associated with
      cytotoxicity depending on the concentration of melatonin in some leukemia cells
      and does not appear to stimulate leukemia cell growth. These pro-oxidant actions
      of melatonin may assist in limiting leukemic cell growth.

PMID- 16448399
TI  - Cyclosporine monitoring in renal transplant recipients with induction therapy: C2
      levels in patients monitored on C0.
AB  - The aim of this retrospective study was to compare the cyclosporine C(2) blood
      levels in renal transplant recipients with induction therapy, monitored on C(0)
      levels during the early and long-term post-transplantation periods in different
      French transplantation centres, to the target values recommended by the
      International Consensus on Neoral and used in the Mo2art study. A retrospective
      study was conducted by the therapeutic drug monitoring (TDM) committee of the
      French Pharmacological Society. Cyclosporine C(0) and C(2) concentrations from
      168 renal transplant recipients were collected at different post-transplantation
      periods by six TDM laboratories of transplantation centres from April 2001 to
      April 2002. Cyclosporine blood levels were determined by fluorescence
      polarization immunoassay (mFPIA, AxSYM, Abbott) or enzyme immunoassay (EMIT, Dade
      Behring). Most patients had C(0) values in the recommended target ranges, with
      C(2) levels below the targets used in the Mo2art study or proposed by the
      International Consensus Conference, both during the early and long-term post
      transplantation periods. Sixty-eight per cent of patients had C(2) below 1,500
      microg/L +/- 20% in the first 2 months post-transplantation and 55% had C(2)
      below 800 microg/L +/- 20% in the late post-transplantation period (>1 year).
      Cyclosporine dose should be increased by 40% on average during the first week
      post-transplantation period and by 50% during the maintenance period to achieve
      the C(2) targets. In France, most renal transplant recipients receiving induction
      agents monitored on C(0) had C(2) levels below the targets recommended by the
      International Consensus Conference. In clinical practice, the optimal therapeutic
      windows for CsA monitoring based on C(2) needs to be more precisely defined, both
      during the early and long-term post-transplantation periods in renal transplant
      recipients receiving induction agents.

PMID- 16448398
TI  - Comparing reagents for efficient transfection of human primary myoblasts: FuGENE
      6, Effectene and ExGen 500.
AB  - This study compared three different synthetic reagents (FuGENE 6, Effectene and
      ExGen 500) for the transfection of human primary myoblasts. We examined the
      efficiency, cytotoxicity and size of the complexes formed in the presence of
      different amounts of vector and DNA and with variable amounts of serum.
      Transfection rates were relatively high for primary cells, especially with FuGENE
      6 (20%), which appeared to be the best transfection reagent for these cells, even
      in the presence of 10% serum. Cultured human myoblasts are an interesting tool
      for studying neuromuscular diseases and are potentially useful for myoblast
      transfer therapy studies. Moreover, the efficiency of these transfection reagents
      in a medium containing 10% serum is promising for possible gene therapy protocols
      for muscle diseases.

PMID- 16448400
TI  - French adaptation and preliminary validation of a questionnaire to evaluate
      understanding of informed consent documents in phase I biomedical research.
AB  - The content of informed consent documents (ICD) is a crucial element in the
      process of providing information to participants in biomedical research. Clear
      comprehension of the information, i.e. the ability to understand its meaning and
      its consequences, is of utmost importance. The objective of this study was to
      describe the different steps in the French adaptation and preliminary validation
      of the Qualite de Comprehension des Formulaires d'information et de consentement
      (QCFic) questionnaire (http://www.lyon.inserm.fr/cic-grenoble) based on the
      American Quality of Informed Consent (QuIC) questionnaire. Adaptation and
      preliminary validation of the QuIC for use in France was composed of five
      principal steps: translation, scientific validation, lexical validation, edition
      of gold-standard answers and a pilot study. Each stage was conducted by
      independent groups of experts, under the coordination of the study board.
      Thirteen questions were added and one was suppressed. Two steps were required for
      the scientific validation and for lexical validation, 21 modifications were
      proposed. Relative to gold-standard answers, the three experts gave the same
      answer for 24 questions and for nine other questions, two of the three gave
      identical answers, which were validated by the study board. Results of a pilot
      study showed a global QCFic score of 88.99 (84.13-90.92) and no specific
      commentary was made about the content of the questions, so no more modification
      needed to be made. A preliminary validated French questionnaire, the QCFic, is
      now available to evaluate the quality of an informed consent document in phase I
      clinical trials. It is quick and easy to use.

PMID- 16448402
TI  - Inbreeding, outbreeding and environmental effects on genetic diversity in 46
      walleye (Sander vitreus) populations.
AB  - Genetic diversity is recognized as an important population attribute for both
      conservation and evolutionary purposes; however, the functional relationships
      between the environment, genetic diversity, and fitness-related traits are poorly
      understood. We examined relationships between selected lake parameters and
      population genetic diversity measures in 46 walleye (Sander vitreus) populations
      across the province of Ontario, Canada, and then tested for relationships between
      six life history traits (in three categories: growth, reproductive investment,
      and mortality) that are closely related to fitness, and genetic diversity
      measures (heterozygosity, d2, and Wright's inbreeding coefficient). Positive
      relationships were observed between lake surface area, growing degree days,
      number of species, and hatchery supplementation versus genetic diversity. Walleye
      early growth rate was the only life history trait significantly correlated with
      population heterozygosity in both males and females. The relationship between FIS
      and male early growth rate was negative and significant (P < 0.01) and marginally
      nonsignificant for females (P = 0.06), consistent with inbreeding depression
      effects. Only one significant relationship was observed for d2: female early
      growth rate (P < 0.05). Stepwise regression models showed that surface area and
      heterozygosity had a significant effect on female early growth rate, while
      hatchery supplementation, surface area and heterozygosity had a significant
      effect on male early growth rate. The strong relationship between lake
      parameters, such as surface area, and hatchery supplementation, versus genetic
      diversity suggests inbreeding and outbreeding in some of the populations;
      however, the weak relationships between genetic diversity and life history traits
      indicate that inbreeding and outbreeding depression are not yet seriously
      impacting Ontario walleye populations.

PMID- 16448403
TI  - Long-term stability and effective population size in North Sea and Baltic Sea cod
      (Gadus morhua).
AB  - DNA from archived otoliths was used to explore the temporal stability of the
      genetic composition of two cod populations, the Moray Firth (North Sea) sampled
      in 1965 and 2002, and the Bornholm Basin (Baltic Sea) sampled in 1928 and 1997.
      We found no significant changes in the allele frequencies for the Moray Firth
      population, while subtle but significant genetic changes over time were detected
      for the Bornholm Basin population. Estimates of the effective population size
      (Ne) generally exceeded 500 for both populations when employing a number of
      varieties of the temporal genetic method. However, confidence intervals were very
      wide and Ne's most likely range in the thousands. There was no apparent loss of
      genetic variability and no evidence of a genetic bottleneck for either of the
      populations. Calculations of the expected levels of genetic variability under
      different scenarios of Ne showed that the number of alleles commonly reported at
      microsatellite loci in Atlantic cod is best explained by Ne's exceeding thousand.
      Recent fishery-induced bottlenecks can, however, not be ruled out as an
      explanation for the apparent discrepancy between high levels of variability and
      recently reported estimates of Ne << 1000. From life history traits and estimates
      of survival rates in the wild, we evaluate the compatibility of the species'
      biology and extremely low Ne/N ratios. Our data suggest that very small Ne's are
      not likely to be of general concern for cod populations and, accordingly, most
      populations do not face any severe threat of losing evolutionary potential due to
      genetic drift.

PMID- 16448404
TI  - Minding the gap: frequency of indels in mtDNA control region sequence data and
      influence on population genetic analyses.
AB  - Insertions and deletions (indels) result in sequences of various lengths when
      homologous gene regions are compared among individuals or species. Although
      indels are typically phylogenetically informative, occurrence and incorporation
      of these characters as gaps in intraspecific population genetic data sets are
      rarely discussed. Moreover, the impact of gaps on estimates of fixation indices,
      such as F(ST), has not been reviewed. Here, I summarize the occurrence and
      population genetic signal of indels among 60 published studies that involved
      alignments of multiple sequences from the mitochondrial DNA (mtDNA) control
      region of vertebrate taxa. Among 30 studies observing indels, an average of 12%
      of both variable and parsimony-informative sites were composed of these sites.
      There was no consistent trend between levels of population differentiation and
      the number of gap characters in a data block. Across all studies, the average
      influence on estimates of PhiST was small, explaining only an additional 1.8% of
      among population variance (range 0.0-8.0%). Studies most likely to observe an
      increase in PhiST with the inclusion of gap characters were those with < 20
      variable sites, but a near equal number of studies with few variable sites did
      not show an increase. In contrast to studies at interspecific levels, the
      influence of indels for intraspecific population genetic analyses of control
      region DNA appears small, dependent upon total number of variable sites in the
      data block, and related to species-specific characteristics and the spatial
      distribution of mtDNA lineages that contain indels.

PMID- 16448405
TI  - Speciation in reverse: morphological and genetic evidence of the collapse of a
      three-spined stickleback (Gasterosteus aculeatus) species pair.
AB  - Historically, six small lakes in southwestern British Columbia each contained a
      sympatric species pair of three-spined sticklebacks (Gasterosteus aculeatus).
      These pairs consisted of a 'benthic' and 'limnetic' species that had arisen
      postglacially and, in four of the lakes, independently. Sympatric sticklebacks
      are considered biological species because they are morphologically, ecologically
      and genetically distinct and because they are strongly reproductively isolated
      from one another. The restricted range of the species pairs places them at risk
      of extinction, and one of the pairs has gone extinct after the introduction of an
      exotic catfish. In another lake, Enos Lake, southeastern Vancouver Island, an
      earlier report suggested that its species pair is at risk from elevated levels of
      hybridization. We conducted a detailed morphological analysis, as well as genetic
      analysis of variation at five microsatellite loci for samples spanning a time
      frame of 1977 to 2002 to test the hypothesis that the pair in Enos Lake is
      collapsing into a hybrid swarm. Our morphological analysis showed a clear
      breakdown between benthics and limnetics. Bayesian model-based clustering
      indicated that two morphological clusters were evident in 1977 and 1988, which
      were replaced by 1997 by a single highly variable cluster. The most recent 2000
      and 2002 samples confirm the breakdown. Microsatellite analysis corroborated the
      morphological results. Bayesian analyses of population structure in a sample
      collected in 1994 indicated two genetically distinct populations in Enos Lake,
      but only a single genetic population was evident in 1997, 2000, and 2002. In
      addition, genetic analyses of samples collected in 1997, 2000, and 2002 showed
      strong signals of 'hybrids'; they were genetically intermediate to parental
      genotypes. Our results support the idea that the Enos Lake species pair is
      collapsing into a hybrid swarm. Although the precise mechanism(s) responsible for
      elevated hybridization in the lake is unknown, the demise of the Enos Lake
      species pair follows the appearance of an exotic crayfish, Pascifasticus
      lenisculus, in the early 1990s.

PMID- 16448406
TI  - Geographic patterns of microsatellite variation in Boechera stricta, a close
      relative of Arabidopsis.
AB  - The genus Boechera is a widespread North American group with great potential for
      studies of ecology and evolution: Boechera is closely related to Arabidopsis and
      exhibits different ecological and reproductive strategies. Boechera stricta
      (previously Arabis drummondii) is a morphologically and genetically well-defined,
      perennial crucifer species. Fifteen natural populations of diploid individuals
      from the Rocky Mountains were analysed using 21 microsatellite loci. In
      accordance with our expectation for this predominately inbreeding species, a high
      F IS value (0.89) was observed. Furthermore, populations of B. stricta were
      highly differentiated, as indicated by F ST = 0.56. Three clusters were
      identified using structure- the majority of populations belonged to either the
      Northern or Southern cluster. Together, the north-south partitioning and evenness
      of genetic variation across the two clusters suggested multiple refugia for this
      perennial herb in the Rocky Mountains. Pleistocene glaciation, together with the
      topographically and climatologically heterogeneous cordillera, has profoundly
      influenced the genetic architecture of B. stricta. Genetic population structure
      was also influenced by relatively recent genome admixture at two levels: within
      species (involving individuals from the Northern and Southern clusters) and
      between species (with the hybridization of B. stricta and Boechera holboellii).
      This complexity of population structure at presumably neutral microsatellite loci
      located throughout the genome in B. stricta provides a baseline against which to
      test whether functional genetic variation is undergoing local adaptive evolution
      throughout the natural species range.

PMID- 16448407
TI  - Isolation by distance and gene flow in the Eurasian badger (Meles meles) at both
      a local and broad scale.
AB  - Eurasian badgers, Meles meles, have been shown to possess limited genetic
      population structure within Europe; however, field studies have detected high
      levels of philopatry, which are expected to increase population structure.
      Population structure will be a consequence of both contemporary dispersal and
      historical processes, each of which is expected to be evident at a different
      scale. Therefore, to gain a greater understanding of gene flow in the badger, we
      examined microsatellite diversity both among and within badger populations,
      focusing on populations from the British Isles and western Europe. We found that
      while populations differed in their allelic diversity, the British Isles
      displayed a similar degree of diversity to the rest of western Europe. The lower
      genetic diversity occurring in Ireland, Norway and Scotland was more likely to
      have resulted from founder effects rather than contemporary population density.
      While there was significant population structure (F ST = 0.19), divergence among
      populations was generally well explained by geographic distance (P < 0.0001)
      across the entire range studied of more than 3000 km. Transient effects from the
      Pleistocene appear to have been replaced by a strong pattern of genetic isolation
      by distance across western Europe, suggestive of colonization from a single
      refugium. Analysis of individuals within British populations through Mantel tests
      and spatial autocorrelation demonstrated that there was significant local
      population structure across 3-30 km, confirming that dispersal is indeed
      restricted. The isolation by distance observed among badger populations across
      western Europe is likely to be a consequence of this restricted local dispersal.

PMID- 16448408
TI  - Assessing reliability of microsatellite genotypes from kit fox faecal samples
      using genetic and GIS analyses.
AB  - Noninvasive faecal DNA sampling has the potential to provide a wealth of
      information necessary for monitoring and managing endangered species while
      eliminating the need to capture, handle or observe rare individuals. However,
      scoring problems, and subsequent genotyping errors, associated with this
      monitoring method remain a great concern as they can lead to misidentification of
      individuals and biased estimates. We examined a kit fox scat data set (353 scats;
      80 genotypes) for genotyping errors using both genetic and GIS analyses, and
      evaluated the feasibility of combining both approaches to assess reliability of
      the faecal DNA results. We further checked the appropriateness of using faecal
      genotypes to study kit fox populations by describing information about foxes that
      we could deduce from the 'acceptable' scat genotypes, and comparing it to
      information gathered with traditional field techniques. Overall, genetic tests
      indicated that our data set had a low rate of genotyping error. Furthermore,
      examination of distributions of scat locations confirmed our data set was
      relatively error free. We found that analysing information on sex primer
      consistency and scat locations provided a useful assessment of scat genotype
      error, and greatly limited the amount of additional laboratory work that was
      needed to identify potentially 'false' scores. 'Acceptable' scat genotypes
      revealed information on sex ratio, relatedness, fox movement patterns, latrine
      use, and size of home range. Results from genetic and field data were consistent,
      supporting the conclusion that our data set had a very low rate of genotyping
      error and that this noninvasive method is a reliable approach for monitoring kit
      foxes.

PMID- 16448409
TI  - Phylogeography and population genetics of the maize stalk borer Busseola fusca
      (Lepidoptera, Noctuidae) in sub-Saharan Africa.
AB  - The population genetics and phylogeography of African phytophagous insects have
      received little attention. Some, such as the maize stalk borer Busseola fusca,
      display significant geographic differences in ecological preferences that may be
      congruent with patterns of molecular variation. To test this, we collected 307
      individuals of this species from maize and cultivated sorghum at 52 localities in
      West, Central and East Africa during the growing season. For all collected
      individuals, we sequenced a fragment of the mitochondrial cytochrome b. We tested
      hypotheses concerning the history and demographic structure of this species.
      Phylogenetic analyses and nested clade phylogeographic analyses (NCPA) separated
      the populations into three mitochondrial clades, one from West Africa, and two-
      Kenya I and Kenya II--from East and Central Africa. The similar nucleotide
      divergence between clades and nucleotide diversity within clades suggest that
      they became isolated at about the same time in three different refuges in sub
      Saharan Africa and have similar demographic histories. The results of mismatch
      distribution analyses were consistent with the demographic expansion of these
      clades. Analysis of molecular variance (amova) indicated a high level of
      geographic differentiation at different hierarchical levels. NCPA suggested that
      the observed distribution of haplotypes at several hierarchical levels within the
      three major clades is best accounted for by restricted gene flow with isolation
      by distance. The domestication of sorghum and the introduction of maize in Africa
      had no visible effect on the geographic patterns observed in the B. fusca
      mitochondrial genome.

PMID- 16448410
TI  - Multiple gene genealogies and AFLPs suggest cryptic speciation and long-distance
      dispersal in the basidiomycete Serpula himantioides (Boletales).
AB  - Serpula himantioides (Boletales, Basidiomycota) produces thin resupinate
      basidiocarps on dead coniferous wood worldwide and causes damage in buildings as
      well. In this study, we present evidence for the existence of at least three
      phylogenetically defined cryptic species (referred to as Sib I-III) within the
      morphospecies S. himantioides, a conclusion based on analyses of sequence data
      from four DNA regions and amplified fragment length polymorphisms (AFLPS). A low
      degree of shared sequence polymorphisms was observed among the three lineages
      indicating a long-lasting separation. The AFLPs revealed two additional subgroups
      within Sib III. Results from mating studies were consistent with the molecular
      data. In Sib III, no correspondence between genetic and geographical distance was
      observed among isolates worldwide, presumably reflecting recent dispersal events.
      Our results indicate that at least two of the lineages (Sib II and Sib III) have
      wide sympatric distributions. A population genetic analysis of Sib III isolates,
      scoring sequence polymorphisms as codominant SNP markers, indicates that
      panmictic conditions exist in the Sib III group. This study supports the view
      that cryptic speciation is a common phenomenon in basidiomycete fungi and that
      phylogenetic species recognition can be a powerful inference to detect cryptic
      species. Furthermore, this study shows that AFLP data are a valuable supplement
      to DNA sequence data in that they may detect a finer level of genetic variation.

PMID- 16448411
TI  - Phylogeography, phylogeny and hybridization in trichechid sirenians: implications
      for manatee conservation.
AB  - Abstract The three living species of manatees, West Indian (Trichechus manatus),
      Amazonian (Trichechus inunguis) and West African (Trichechus senegalensis), are
      distributed across the shallow tropical and subtropical waters of America and the
      western coast of Africa. We have sequenced the mitochondrial DNA control region
      in 330 Trichechus to compare their phylogeographic patterns. In T. manatus we
      observed a marked population structure with the identification of three haplotype
      clusters showing a distinct spatial distribution. A geographic barrier
      represented by the continuity of the Lesser Antilles to Trinidad Island, near the
      mouth of the Orinoco River in Venezuela, appears to have restricted the gene flow
      historically in T. manatus. However, for T. inunguis we observed a single
      expanding population cluster, with a high diversity of very closely related
      haplotypes. A marked geographic population structure is likely present in T.
      senegalensis with at least two distinct clusters. Phylogenetic analyses with the
      mtDNA cytochrome b gene suggest a clade of the marine Trichechus species, with T.
      inunguis as the most basal trichechid. This is in agreement with previous
      morphological analyses. Mitochondrial DNA, autosomal microsatellites and
      cytogenetic analyses revealed the presence of hybrids between the T. manatus and
      T. inunguis species at the mouth of the Amazon River in Brazil, extending to the
      Guyanas and probably as far as the mouth of the Orinoco River. Future
      conservation strategies should consider the distinct population structure of
      manatee species, as well as the historical barriers to gene flow and the likely
      occurrence of interspecific hybridization.

PMID- 16448412
TI  - Testing phylogeographic predictions on an active volcanic island: Brachyderes
      rugatus (Coleoptera: Curculionidae) on La Palma (Canary Islands).
AB  - Volcanic islands with well-characterized geological histories can provide ideal
      templates for generating and testing phylogeographic predictions. Many studies
      have sought to utilize these to investigate patterns of colonization and
      speciation within groups of closely related species across a number of islands.
      Here we focus attention within a single volcanic island with a well-characterized
      geological history to develop and test phylogeographic predictions. We develop
      phylogeographic predictions within the island of La Palma of the Canary Islands
      and test these using 69 haplotypes from 570 base pairs of mitochondrial DNA
      cytochrome oxidase II sequence data for 138 individuals of Brachyderes rugatus
      rugatus, a local endemic subspecies of curculionid beetle occurring throughout
      the island in the forests of Pinus canariensis. Although geological data do
      provide some explanatory power for the phylogeographic patterns found, our
      network-based analyses reveal a more complicated phylogeographic history than
      initial predictions generated from data on the geological history of the island.
      Reciprocal illumination of geological and phylogeographic history is also
      demonstrated with previous geological speculation gaining phylogeographic
      corroboration from our analyses.

PMID- 16448413
TI  - Axes of differentiation in the bower-building cichlids of Lake Malawi.
AB  - The 500-1000 cichlid species endemic to Lake Malawi constitute one of the most
      rapid and extensive radiations of vertebrates known. There is a growing debate
      over the role natural and sexual selection have played in creating this
      remarkable assemblage of species. Phylogenetic analysis of the Lake Malawi
      species flock has been confounded by the lack of appropriate morphological
      characters and an exceptional rate of speciation, which has allowed ancestral
      molecular polymorphisms to persist within species. To overcome this problem we
      used amplified fragment length polymorphism (AFLP) to reconstruct the evolution
      of species within three genera of Lake Malawi sand-dwelling cichlids that
      construct elaborate male display platforms, or bowers. Sister taxa with distinct
      bower morphologies, and that exist in discrete leks separated by only 1-2 m of
      depth, are divergent in both sexually selected and ecological traits. Our
      phylogeny suggests that the forces of sexual and ecological selection are
      intertwined during the speciation of this group and that specific bower
      characteristics and trophic morphologies have evolved repeatedly. These results
      suggest that trophic morphology and bower form may be inappropriate characters
      for delineating taxonomic lineages. Specifically the morphological characters
      used to describe the genera Lethrinops and Tramitichromis do not define
      monophyletic clades. Using a combination of behavioural and genetic characters,
      we were able to identify several cryptic cichlid species on a single beach, which
      suggests that sand dweller species richness has been severely underestimated.

PMID- 16448414
TI  - Comparative phylogeography across two trophic levels: the oak gall wasp Andricus
      kollari and its chalcid parasitoid Megastigmus stigmatizans.
AB  - Insect parasitoids are important components of many terrestrial ecosystems.
      However, relatively little is known about the mechanisms responsible for
      structuring their populations. Here we investigate the ability of Megastigmus
      stigmatizans, an oak gall wasp parasitoid, to track its host Andricus kollari
      over two different timescales, and examine its current population structure
      across a divide in host population structure. The divide represents a transition
      in gall wasp host-plant species and offers the opportunity to examine whether the
      split, which divides gall wasp populations, manifests itself in the next trophic
      level. Analysis of mitochondrial haplotype data for parasitoid and host reveals:
      (i) A similar phylogeographic population structure for both, with Iberian
      populations more derived with respect to more eastern populations. (ii) It is
      likely that the host colonized the Iberian refuge earlier than the parasitoid,
      probably by at least one glacial cycle. (iii) Recent range expansion of central
      European host populations northwards has resulted in pursuit by parasitoids from
      the same geographic origin. (iv) In addition, Iberian parasitoid populations have
      crossed a major divide in host population structure to invade northern Europe.
      Such human-facilitated escape from natural refugial distributions may have
      important implications for the composition and structure of northern European
      gall wasp communities.

PMID- 16448415
TI  - Inefficient photosynthesis in the Mediterranean orchid Limodorum abortivum is
      mirrored by specific association to ectomycorrhizal Russulaceae.
AB  - Among European Neottieae, Limodorum abortivum is a common Mediterranean orchid.
      It forms small populations with a patchy distribution in woodlands, and is
      characterized by much reduced leaves, suggesting a partial mycoheterotrophy. We
      have investigated both the photosynthetic abilities of L. abortivum adult plants
      and the diversity of mycorrhizal fungi in Limodorum plants growing in different
      environments and plant communities (coniferous and broadleaf forests) over a wide
      geographical and altitudinal range. Despite the presence of photosynthetic
      pigments, CO2 fixation was found to be insufficient to compensate for respiration
      in adult plants. Fungal diversity was assessed by morphological and molecular
      methods in L. abortivum as well as in the related rare species Limodorum
      trabutianum and Limodorum brulloi. Phylogenetic analyses of the fungal internal
      transcribed spacer (ITS) sequences, obtained from root samples of about 80
      plants, revealed a tendency to associate predominantly with fungal symbionts of
      the genus Russula. Based on sequence similarities with known species, most root
      endophytes could be ascribed to the species complex encompassing Russula delica,
      Russula chloroides, and Russula brevipes. Few sequences clustered in separate
      groups nested within Russula, a genus of ectomycorrhizal fungi. The morphotypes
      of ectomycorrhizal root tips of surrounding trees yielded sequences similar or
      identical to those obtained from L. abortivum. These results demonstrate that
      Limodorum species with inefficient photosynthesis specifically associate with
      ectomycorrhizal fungi, and appear to have adopted a nutrition strategy similar to
      that known from achlorophyllous orchids.

PMID- 16448416
TI  - Intracolony variation of bacterial gut microbiota among castes and ages in the
      fungus-growing termite Macrotermes gilvus.
AB  - The fungus-growing termites Macrotermes cultivate the obligate ectosymbiontic
      fungi, Termitomyces. While their relationship has been extesively studied, little
      is known about the gut bacterial symbionts, which also presumably play a crucial
      role for the nutrition of the termite host. In this study, we investigated the
      bacterial gut microbiota in two colonies of Macrotermes gilvus, and compared the
      diversity and community structure of bacteria among nine termite morphotypes,
      differing in caste and/or age, using terminal restriction fragment length
      polymorphism (T-RFLP) and clonal analysis of 16S rRNA. The obtained molecular
      community profiles clustered by termite morphotype rather than by colony, and the
      clustering pattern was clearly more related to a difference in age than to caste.
      Thus, we suggest that the bacterial gut microbiota change in relation to the food
      of the termite, which comprises fallen leaves and the fungus nodules of
      Termitomyces in young workers, and leaves degraded by the fungi, in old workers.
      Despite these intracolony variations in bacterial gut microbiota, their T-RFLP
      profiles formed a distinct cluster against those of the fungus garden, adjacent
      soil and guts of sympatric wood-feeding termites, implying a consistency and
      uniqueness of gut microbiota in M. gilvus. Since many bacterial phylotypes from
      M. gilvus formed monophyletic clusters with those from distantly related termite
      species, we suggest that gut bacteria have co-evolved with the termite host and
      form a microbiota specific to a termite taxonomic and/or feeding group, and
      furthermore, to caste and age within a termite species.

PMID- 16448417
TI  - Wolbachia and other endosymbiont infections in spiders.
AB  - Maternally inherited endosymbiotic bacteria, such as Wolbachia, Rickettsia and
      Spiroplasma, have been shown to have wide-ranging effects on the reproduction of
      their hosts. We present data on the presence of each of these sorts of bacteria
      in spiders, a group for which there are currently few data, but where such
      infections could explain many observed reproductive characteristics, such as sex
      ratio skew. The Wolbachia and Spiroplasma variants that we find in spiders belong
      to the same clades previously found to infect other arthropods, but many of the
      rickettsias belong to two, novel, hitherto spider-specific bacterial lineages. We
      find evidence for coexistence of different bacterial types within species, and in
      some cases, within individuals. We suggest that spiders present a useful
      opportunity for studying the effect of these sorts of bacteria on the evolution
      of host traits, such as those that are under sexual selection.

PMID- 16448418
TI  - MHC gene configuration variation in geographically disparate populations of
      California sea lions (Zalophus californianus).
AB  - Major histocompatibility complex (MHC) class II DRB genotypes were examined in
      two geographically isolated populations of California sea lions (Zalophus
      californianus) (Gulf of California and California coastal Pacific Ocean). Genomic
      DNA from 227 California sea lions was examined using eight sequence-specific
      primer (SSP) pairs flanking the putative peptide-binding site. A total of 40
      different Zaca-DRB genotype configurations were identified among the 227
      individuals. Using SSP-PCR, significant differences were found between coastal
      California and Gulf of California Zalophus populations in numbers of DRB
      sequences per individual and configuration of sequences within individuals.
      Additionally, unique local patterns of MHC diversity were identified among the
      Midriff Island animals. These population differences are consistent with either
      ecologically distinct patterns of selection pressures and/or geographical
      isolation. The consequences of these partitioned MHC configurations at the
      population level are as yet unknown; however, the worldwide increase in emerging
      marine diseases lends urgency to their examination.

PMID- 16448419
TI  - Screening for rapidly evolving genes in the ectomycorrhizal fungus Paxillus
      involutus using cDNA microarrays.
AB  - We have examined the variations in gene content and sequence divergence that
      could be associated with symbiotic adaptations in the ectomycorrhizal fungus
      Paxillus involutus and the closely related species Paxillus filamentosus. Strains
      with various abilities to form mycorrhizae were analysed by comparative genomic
      hybridizations using a cDNA microarray containing 1076 putative unique genes of
      P. involutus. To screen for genes diverging at an enhanced and presumably non
      neutral rate, we implemented a simple rate test using information from both the
      variations in hybridizations signal and data on sequence divergence of the
      arrayed genes relative to the genome of Coprinus cinereus. C. cinereus is a free
      living saprophyte and is the closest evolutionary relative to P. involutus that
      has been fully sequenced. Approximately 17% of the genes investigated were
      detected as rapidly diverging within Paxillus. Furthermore, 6% of the genes
      varied in copy numbers between the analysed strains. Genome rearrangements
      associated with this variation including duplications and deletions may also play
      a role in adaptive evolution. The cohort of divergent and duplicated genes showed
      an over-representation of either orphans, genes whose products are located at
      membranes, or genes encoding for components of stress/defence reactions. Some of
      the identified genomic changes may be associated with the variation in host
      specificity of ectomycorrhizal fungi. The proposed procedure could be generally
      applicable to screen for rapidly evolving genes in closely related strains or
      species where at least one has been sequenced or characterized by expressed
      sequence tag analysis.

PMID- 16448420
TI  - Polymorphism of visual pigment genes in the muriqui (Primates, Atelidae).
AB  - Colour vision varies within the family Atelidae (Primates, Platyrrhini), which
      consists of four genera with the following cladistic relationship:
      {Alouatta[Ateles (Lagothrix and Brachyteles)]}. Spider monkeys (Ateles) and
      woolly monkeys (Lagothrix) are characteristic of platyrrhine monkeys in
      possessing a colour vision polymorphism. The polymorphism results from allelic
      variation of the single-locus middle-to-long wavelength (M/L) cone opsin gene on
      the X-chromosome. The presence in the population of alleles coding for different
      M/L photopigments results in a variety of colour vision phenotypes. Such a
      polymorphism is absent in howling monkeys (Alouatta), which, alone among
      platyrrhines, acquired uniform trichromatic vision similar to that of Old World
      monkeys, apes, and humans through opsin gene duplication. Dietary and
      morphological similarities between howling monkeys and muriquis (Brachyteles)
      raise the possibility that the two genera share a similar form of colour vision,
      uniform trichromacy. Yet parsimony predicts that the colour vision of Brachyteles
      will resemble the polymorphism present in Lagothrix and Ateles. Here we test this
      assumption. We obtained DNA from the blood or faeces of 18 muriquis and sequenced
      exons 3 and 5 of the M/L opsin gene. Our results affirm the existence of a single
      M/L cone opsin gene in the genus Brachyteles. We detected three alleles with
      predicted lambdamax values of 530, 550, and 562 nm. Two females were heterozygous
      and are thus predicted to have different types of M/L cone pigment. We discuss
      the implication of this result towards understanding the evolutionary ecology of
      trichromatic vision.

PMID- 16448421
TI  - Fine-scale genetic structure and gene dispersal inferences in 10 neotropical tree
      species.
AB  - The extent of gene dispersal is a fundamental factor of the population and
      evolutionary dynamics of tropical tree species, but directly monitoring seed and
      pollen movement is a difficult task. However, indirect estimates of historical
      gene dispersal can be obtained from the fine-scale spatial genetic structure of
      populations at drift-dispersal equilibrium. Using an approach that is based on
      the slope of the regression of pairwise kinship coefficients on spatial distance
      and estimates of the effective population density, we compare indirect gene
      dispersal estimates of sympatric populations of 10 tropical tree species. We re
      analysed 26 data sets consisting of mapped allozyme, SSR (simple sequence
      repeat), RAPD (random amplified polymorphic DNA) or AFLP (amplified fragment
      length polymorphism) genotypes from two rainforest sites in French Guiana. Gene
      dispersal estimates were obtained for at least one marker in each species,
      although the estimation procedure failed under insufficient marker polymorphism,
      limited sample size, or inappropriate sampling area. Estimates generally suffered
      low precision and were affected by assumptions regarding the effective population
      density. Averaging estimates over data sets, the extent of gene dispersal ranged
      from 150 m to 1200 m according to species. Smaller gene dispersal estimates were
      obtained in species with heavy diaspores, which are presumably not well
      dispersed, and in populations with high local adult density. We suggest that
      limited seed dispersal could indirectly limit effective pollen dispersal by
      creating higher local tree densities, thereby increasing the positive correlation
      between pollen and seed dispersal distances. We discuss the potential and
      limitations of our indirect estimation procedure and suggest guidelines for
      future studies.

PMID- 16448423
TI  - Retrograde endoscopic laser therapy and ureteroscopic surveillance for
      transitional cell carcinoma of the upper urinary tract.
AB  - OBJECTIVE: To investigate the efficacy of endoscopic laser therapy and
      ureteroscopic surveillance for transitional cell carcinoma (TCC) of the upper
      urinary tract. METHODS: Tumors of the upper urinary tract were detected at
      ureteroscopy. After TCC was diagnosed by biopsy, retrograde endoscopic laser
      therapy was performed. Recurrent tumors were treated endoscopically and the
      patients were followed by ureteroscopic surveillance at 3- to 6-month intervals.
      RESULTS: Seven patients underwent ureteroscopic treatment. The tumor was grade 1
      in five patients and grade 2 in two patients. The average tumor size was 1.3 cm.
      One patient with large, multifocal tumors died of metastatic disease, and one
      died of an unrelated cause. One patient requested nephroureterectomy after
      endoscopic treatment. The remaining four patients were followed up for a mean of
      32 months after initial treatment. Each patient received an average of 5.3
      ureteroscopic surveillance procedures while 3.3 recurrences on average were
      detected. Recurrence occurred in all the patients who showed normal radiographic
      findings. Urine cytology was also of little value in predicting tumor recurrence,
      except in one patient with carcinoma in situ. The recurrent tumors detected by
      ureteroscopy were successfully treated by repeated endoscopic procedures. After
      the follow up, three patients remained alive with no signs indicative of disease,
      but one patient with an initial grade 2 tumor died of recurrence after 30 months.
      CONCLUSIONS: Given that ureteroscopic evaluation is essential for surveillance
      after endoscopic treatment of upper urinary tract TCC because of residual concern
      about recurrence, patients treated endoscopically should be recommended to
      undergo long-term endoscopic follow up.

PMID- 16448424
TI  - Radical retropubic prostatectomy through a minimal incision with portless
      endoscopy: our initial experience.
AB  - Twenty-one patients with clinically localized prostate cancer underwent
      minilaparotomy radical retropubic prostatectomy through a single 5-cm midline or
      Pfannenstiel incision. A 30 degrees laparoscope was usually positioned around the
      edge of the incision to facilitate the procedure. The mean operating time was 255
      min. The mean blood loss was 859 mL, and no patient required an allogenic blood
      transfusion. Postoperative pain was noticeably reduced, especially in the
      Pfannenstiel incision group. Endoscope-assisted minilaparotomy did not involve a
      learning curve, and could be useful for most urologic surgeons as minimally
      invasive surgery.

PMID- 16448425
TI  - Transperineal extended biopsy improves the clinically significant prostate cancer
      detection rate: a comparative study of 6 and 12 biopsy cores.
AB  - BACKGROUND: We evaluated the improvement in the rate of prostate cancer detection
      when using a 12-core transperineal biopsy protocol including transitional zone
      biopsy. METHODS: Between April 2003 and November 2004, 247 consecutive men
      underwent transperineal systemic 12-core biopsy of the prostate. Six cores were
      obtained at the peripheral zone, four at the transitional zone and two at the
      apex. We examined the cancer detection rate in each of the 12 cores, and also
      determined the improvement of cancer detection resulting from the extensive 12
      core versus standard 6-core biopsy. RESULTS: Using the extensive 12-core biopsy,
      prostate cancer was detected in 98 cases (39.7%). Prostate-specific antigen
      (PSA), PSA density, the positive rate in digital rectal examination and
      transrectal ultrasound findings were significantly higher in the prostate cancer
      group than in the non-prostate cancer group, and prostate volume was larger in
      non-prostate cancer group. Every site showed almost the same positive rate,
      between 17.8 and 21.5%. There were 20 cases which were positive in the extended
      biopsy, but negative in the sextant. The detection improved significantly
      (20.4%). The improvement of cancer detection in extended biopsy was better in men
      with PSA levels of 10 ng/mL or less (28.9%), PSA density 0.3 or less (25.8%),
      negative digital rectal examination (23.3%), and negative transrectal ultrasound
      (21.6%). Of these twenty patients, no cases with insignificant tumor were
      detected in the six prostatectomy cases. In particular, three cases of the six
      were transitional-zone-only cancer. CONCLUSION: Transperineal extended 12-core
      biopsy including 4 transitional zone cores is a more useful procedure than
      transperineal 6-core biopsy. Routine transitional zone biopsy, that is different
      from transrectal biopsy, might be useful for detecting biologically significant
      cancer.

PMID- 16448426
TI  - Clinical efficacy of an alpha1A/D-adrenoceptor blocker (naftopidil) on overactive
      bladder symptoms in patients with benign prostatic hyperplasia.
AB  - AIM: We evaluated the efficacy of an alpha1a/d blocker, naftopidil, on storage
      symptoms in patients with benign prostatic hyperplasia (BPH), using
      frequency/volume charts (FVC). METHODS: A total of 81 patients with BPH (52-91
      years, mean age 69.0 years) were studied. The inclusion criteria were: (i) one or
      more episode(s) of urinary urgency/day; (ii) a score of eight or more points on
      the International Prostate Symptom Score (I-PSS); and (iii) three or more points
      in any of the scores for three items (frequency, nocturia, and urgency) of the I
      PSS. The patients received 50-75 mg/day of naftopidil for 6 weeks. All the
      patients were examined for 2-day FVC before and after the administration of
      naftopidil. I-PSS, quality of life index, and uroflowmetry were also evaluated.
      RESULTS: Total I-PSS decreased from 19.1 to 10.5 points (P < 0.0001), with
      significant improvement of both storage and voiding symptom scores (P < 0.0001,
      both). The score for urgency decreased from 3.1 to 1.4 (P < 0.0001). Daytime and
      night-time frequency decreased from 9.3 to 8.0 (P < 0.0001) and from 2.7 to 2.0
      (P = 0.0009), respectively. Mean volume/void increased from 174.0 to 188.6 mL (P
      = 0.0453). Nocturia decreased from 3.2 to 2.3 (P < 0.0001) in 40 patients who
      suffered from nocturia two times or more. Notably, significant improvement of
      nocturia was observed in the patients both with and without nocturnal polyuria (P
      = 0.0006 and 0.0135, respectively). CONCLUSION: The alpha1a/d blocker naftopidil
      improves not only voiding symptoms but also storage symptoms, and is effective
      for nocturia in patients with BPH regardless of the existence of nocturnal
      polyuria.

PMID- 16448427
TI  - Plasmakinetic prostate resection in the treatment of benign prostate hyperplasia:
      results of 1-year follow up.
AB  - AIM: In our randomized prospective study, we aimed to evaluate the efficiency of
      plasmakinetic resection of prostate (PKRP) by comparing the preoperative and
      postoperative results of the transurethral resection of prostate (TURP) and PKRP
      techniques which we administered in patients with benign prostate hyperplasia
      (BPH) in our clinic. METHODS: Of 57 patients for whom we thought an operative
      intervention was necessary, 30 cases in the first group had a TURP and 24 cases
      in the second group had a PKRP. International prostate symptom scores (I-PSS),
      uroflowmetry, measurement of residual urine amount and ultrasonography were
      performed for each patient both preoperatively and postoperatively (first month
      and first year). Operation times, urethral catheterization times, preoperative
      and postoperative Hb, Htc and serum Na values of the patients were compared and
      the complications of the groups were also compared. RESULTS: On first month and
      first year follow up between the groups, there was no significant statistical
      difference in I-PSS, maximum flow rate, average flow, residual urine and size of
      the prostate. The decrease in serum Na level was found to be significantly higher
      in the TURP group (P < 0.05). The operation times were not significantly
      different between the groups. While the postoperative catheterization time was
      75.7 h in TURP group, it was found to be 42 h in PKRP group and it was clear that
      catheterization time was significantly shorter (P < 0001). CONCLUSION: It is
      obvious that PKRP is as efficient as TURP and it has a similar morbidity. In our
      opinion, PKRP makes a promising treatment for BPH with its advantages, such as
      early removal of postoperative urethral catheter, a shorter hospital stay and the
      absence of TUR syndrome risk.

PMID- 16448428
TI  - Bacteriuria, pyuria and bacteremia frequency following outpatient cystoscopy.
AB  - AIM: The assumed necessity of antimicrobial prophylaxis prior to cystoscopy is
      controversial. In this study, the rate of bacteriuria, pyuria and bacteremia in
      outpatients who underwent cystoscopy without antimicrobial prophylaxis is
      investigated prospectively. METHODS: The study included 75 patients who underwent
      cystoscopy for various indications and had sterile urine prior to intervention. A
      clean midstream urine sample was obtained 24 h before and 48 h after the
      procedure. Blood cultures were taken 1 h after cystoscopy. Patients were
      questioned for newly developed symptoms 48 h after cystoscopy. Blood cultures
      were taken again from patients who presented with fever. RESULTS: Six patients
      (8%) developed significant bacteriuria, and six patients (8%) developed pyuria
      without significant bacteriuria. Bacteremia was not determined in any of the
      patients. The association between presence of pyuria prior to the procedure and
      development of bacteriuria after the procedure was significant (P < 0.05). Four
      patients out of six who had bacteriuria were asymptomatic. In our study we found
      significant bacteriuria after cystoscopy in 8% of patients, and no bacteremia.
      CONCLUSIONS: Thus we conclude that cystoscopy is a safe and well-tolerated
      procedure. Antimicrobial prophylaxis should not be administrated unless specific
      indications are present.

PMID- 16448429
TI  - Videomanometry of the pelvic organs: a comparison of the normal lower urinary and
      gastrointestinal tracts.
AB  - BACKGROUND: Both the lower urinary tract (LUT) and the caudal part of the lower
      gastrointestinal tract (LGIT) are innervated by the sacral spinal cord. We aimed
      to compare the normal physiology of the LUT and LGIT using the same
      videomanometry method. METHODS: We recruited fifteen healthy volunteers (eight
      men and seven women; mean age, 60 years). The videomanometric measures included
      fluoroscopic images, subtracted bladder/rectal pressures, urethral/anal sphincter
      pressures, sphincter electromyography, and urinary/fecal flow. RESULTS: During
      the resting phase, the urethral/anal sphincter pressures showed almost the same
      values (mean, 70 cmH2O and 68 cmH2O, respectively). During the storage phase, the
      volumes at first sensation and maximum capacity for the LGIT (129 mL and 320 mL)
      were slightly smaller than those for the LUT (170 mL and 405 mL). Compliance of
      the LGIT (65 mL/cmH2O) was almost as high as that of the LUT (99 mL/cmH2O).
      However, the LGIT showed spontaneous phasic rectal contractions (SPRC) that were
      never seen in the bladder. None of the subjects experienced leakage during
      bladder/rectal filling. During the evacuation phase, rectal contraction on
      defecation (14 cmH2O) was present, but was weaker than bladder contraction on
      micturition (42 cmH2O; P < 0.01). Abdominal strain on defecation (70 cmH2O) was
      greater than that on micturition (25 cmH2O; P < 0.01). Sphincter pressure
      increase on defecation (13 cmH2O) was greater than that on micturition (-52
      cmH2O). An illustrative case of SPRC that were seen during urodynamic recording
      was shown. CONCLUSION: SPRC and abdominal strain are features of the LGIT,
      whereas micturition bladder contraction is a feature of the LUT. These features
      can aid in understanding the possible rectal 'artifacts' of videourodynamics and
      neurogenic pelvic organ dysfunction.

PMID- 16448431
TI  - Sexual activity in Korean male patients on clean intermittent catheterization
      with neurogenic bladder due to spinal cord injury.
AB  - BACKGROUND: The aim of this study was to assess the sexual function and activity
      in male patients on clean intermittent catheterization with neurogenic bladder
      due to spinal cord injury. METHODS: Eighty-nine patients (mean age 37.6 years
      with a range of 18-66) were included in the study. We requested all subjects to
      complete a questionnaire including the 5-item version of the International Index
      of Erectile Function (IIEF-5). RESULTS: Of 89 patients, 60 (67.4%) reported
      having attempted no sexual intercourse over the past 6 months and 28 (31.5%)
      presented with IIEF-5 scores less than or equal to 21 points. When subjects were
      stratified according to the years since injury, 50.0% (16 of 32) with less than 2
      years post-injury had no sexual activity, while 77.2 (44 of 57) with 2 years or
      more post-injury did (P = 0.027). Patients with sexual activity were 40.4% (23 of
      57) and 18.8% (6 of 32) in patients who were able and unable to perform self
      catheterization, respectively (P = 0.037). Patients with less than 2 years post
      injury had 3.3-fold higher risk (odds ratio 3.33; 95% confidence interval 1.01
      10.97; P = 0.048) of no sexual activity than those with 2 years or more post
      injury on the multivariate model. The other parameters were not appreciably
      related to sexual activity. CONCLUSION: Our results demonstrate that sexual
      activity as well as erectile function is poor in this population. In addition,
      our findings suggest that years since injury may influence sexual activity of
      patients with spinal cord injury.

PMID- 16448430
TI  - Nocturnal enuresis and overactive bladder in children: an epidemiological study.
AB  - AIMS: To investigate the prevalence and characteristics of nocturnal enuresis
      (NE) and to examine the prevalence of overactive bladder (OAB) symptoms in
      primary schoolchildren. METHODS: After conducting an anonymous questionnaire
      survey about voiding habits and bowel habits in primary schoolchildren, a total
      of 6917 schoolchildren belonging to 11 primary schools were randomly enrolled in
      the survey. According to the International Continence Society, we defined NE as
      any involuntary loss of urine during sleep, occurring more frequently than once
      per month. Children with NE were subdivided into two groups, monosymptomatic NE
      (MNE) and enuretic syndrome (ES). To evaluate the characteristic differences of
      MNE and ES, we assessed the relationships between NE and voiding habits, and
      episodes of cystitis and constipation. Overactive bladder was defined as
      increased daytime frequency and/or urge urinary incontinence, and its prevalence
      was investigated. RESULTS: The response rate to the questionnaire was 76.4%. The
      prevalence of NE was 5.9% and was inversely related to increasing age.
      Monosymptomatic NE comprised 59.4% of NE cases. The annual spontaneous resolution
      rate of MNE was higher than that of ES. Increased daytime frequency, a history of
      cystitis and infrequent bowel habits were not related to MNE, but were
      significantly related to ES. The prevalence of OAB was 17.8%. Children with a
      history of cystitis had a significantly higher rate of OAB than children without
      it. CONCLUSIONS: Overall, NE and OAB were detected in 5.9% and 17.8% of primary
      schoolchildren, respectively. The link between NE and OAB symptoms, urinary tract
      infections and constipation deserves more attention.

PMID- 16448432
TI  - Establishment and characterization of human urothelial cancer xenografts in
      severe combined immunodeficient mice.
AB  - AIM: To establish and characterize a murine xenograft model of human urothelial
      cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation.
      METHODS: Pieces of 30 freshly resected urothelial tumors (24 obtained from
      bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID
      mice, and xenograft tumors were passed in tumorigenic cases. At each passage,
      histopathology, TP53 mutational status assessed by yeast p53 functional assay,
      and the Ki-67 labeling index (LI) were examined to evaluate the preservation of
      original features. A growth delay assay after single-dose irradiation was
      performed in four representative xenografts. RESULTS: Tumor growth was observed
      in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas
      similar to the original tumors, whereas the other 3 were Epstein-Barr virus
      associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No
      correlation was found between the tumor take rate and the clinicopathologic
      features, TP53 mutational status, or Ki-67 LI of the patients' tumors. Of these
      15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53
      mutational status remained stable during the passages, and the Ki-67 LI of eight
      xenografts was within a range of 50% of the LI of the original tumors, although
      the other three xenografts increased by over 50%. Specific growth delay after
      irradiation, independent of the original tumor growth speed and Ki-67 LI, was
      observed in four xenografts. CONCLUSIONS: SCID mice are useful recipients for
      investigations of human urothelial cancer with a wide biological range. This easy
      to-handle xenograft system can help to develop a better in vivo preclinical
      evaluation system for therapeutic agents as well as the investigation of tumor
      pathophysiology.

PMID- 16448433
TI  - Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal
      smooth muscle in rabbits.
AB  - BACKGROUND: The incidence of hormonal dysfunction as a cause of impotence remains
      controversial. However, several recent studies have reported evidence of hormonal
      abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to
      occur in 6% of impotent men. METHODS: In the present study, we examined nitrergic
      responses in hypothyroidism in rabbit corpus cavernosum and compared them with
      controls. RESULTS: Carbachol-induced relaxation responses and electrical field
      stimulation (EFS)-induced frequency-dependent relaxations decreased significantly
      in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)-induced
      relaxation responses did not change significantly in hypothyroid rabbits. The
      contraction responses of phenylephrine and EFS-induced frequency-dependent
      contractions were significantly decreased in the hypothyroid group. CONCLUSIONS:
      We can speculate that the reduction of relaxant responses to EFS and carbachol in
      hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from
      nitrergic nerves and endothelium or a reduction of muscarinic receptor density.
      Also, decreases in contraction responses may depend on diminished adrenoceptor
      density.

PMID- 16448434
TI  - Gastric diverticulum preoperatively diagnosed as one of two left adrenal
      adenomas.
AB  - A 47-year-old man was diagnosed with primary aldosteronism due to two left
      adrenal adenomas, suggested on computed tomography (CT) to be located at the
      upper and lower adrenal portion. However, adosterol scintigraphy revealed
      negligible uptake at the upper portion of the left adrenal. Laparoscopic left
      adrenalectomy was performed, but macroscopic examination of the specimen revealed
      only one adrenal tumor. Continued surgical exploration detected another mass
      between the spleen and the stomach, which was demonstrated to be continuous with
      the stomach and was eventually diagnosed as a gastric diverticulum.
      Postoperatively, aldosteronism resolved and repeat CT revealed staining of the
      adrenal pseudotumor when oral contrast was administered. Since organs located
      near the adrenals can simulate adrenal tumors, caution must be exercised in
      interpreting suprarenal masses on CT. To our knowledge, this is the first
      reported case of concurrent pseudotumor and true tumor of the ipsilateral
      adrenal.

PMID- 16448435
TI  - Renal tuberculosis simulating xanthogranulomatous pyelonephritis with contagious
      hepatic involvement.
AB  - Xanthogranulomatous pyelonephritis (XGPN) is a chronic renal infection typically
      associated with nephrolithiasis and a non-functioning kidney. Renal tuberculosis
      is a major cause of morbidity in developing countries. Despite recent advances in
      diagnosis, it is sometimes difficult to differentiate renal tuberculosis
      preoperatively from XGPN. We present herewith a case report of a patient who was
      preoperatively diagnosed with a right non-functioning kidney due to renal
      calculus with stage 3 XGPN and adjacent liver abscess on computed tomography.
      Subsequent histopathological examination of the nephrectomised specimen revealed
      renal tuberculosis. To our knowledge this is the first case of renal tuberculosis
      spreading to the liver and causing liver abscess formation which was misdiagnosed
      as XGPN preoperatively.

PMID- 16448437
TI  - Malignant peripheral nerve sheath tumor of the kidney.
AB  - Malignant peripheral nerve sheath tumors are rare in the genitourinary organs,
      with few reports of occurrence in the kidney. We describe a patient with a renal
      malignant peripheral nerve sheath tumor, discovered after excision of a malignant
      peripheral nerve sheath scalp lesion, with additional masses in the lung and
      shoulder on metastatic evaluation. This patient underwent neoadjuvant intravenous
      doxorubicin therapy, followed by surgical resection of the scalp, lung and
      shoulder lesions in addition to a radical nephrectomy.

PMID- 16448436
TI  - Retroperitoneoscopic partial nephrectomy using radiofrequency ablation.
AB  - Two patients with renal tumors underwent retroperitoneoscopic partial
      nephrectomy. The renal tumors were initially treated with radiofrequency
      ablation. This method allowed tumor excision to be achieved without clamping the
      renal pedicle. Residual renal function was well maintained as determined by
      enhanced computed tomography scanning and measurement of the serum creatinine
      level. There were no complications such as vascular damage or collecting system
      injury. The pathological diagnosis was clear cell carcinoma (pT1) in Patient 1
      and was not determined in Patient 2 because of entire ablation. No recurrence has
      been observed after 3 years and 2 years of follow up, respectively.
      Radiofrequency ablation was useful for control of local bleeding during
      retroperitonaoscopic partial nephrectomy.

PMID- 16448438
TI  - Primary retrovesical hydatidosis causing chronic renal failure.
AB  - Hydatidosis is an endemic, widely distributed zoonosis, which involves the liver,
      lung and other organs. Isolated retrovesical involvement is an uncommon location
      of occurrence, which may rarely cause chronic renal failure. We profile the
      presentation, management and outcome of three such cases.

PMID- 16448439
TI  - Obstruction of the ileal ureter by mesenteric vessels occurring 5 years after
      total ureteral substitution for bilateral ureteral stenosis due to systemic lupus
      erythematosus.
AB  - We previously reported a case of bilateral ureteral stenosis accompanied by
      systemic lupus erythematosus, which was successfully managed by total ureteral
      reconstruction using a segment of the ileum. Herein, we describe an unusual
      complication in the same patient, which we experienced 5 years after the ileal
      ureteral substitution. Left-sided back pain repeated together with transient
      obstruction of the ileal ureter interposed between the right and left renal
      pelvis. Consequently, exploratory laparotomy revealed that left colic vessels
      oppressed and caused obstruction, and the obstructed ileal ureter was released by
      reconstitution of these vessels instead of re-anastomosis of the ileal ureter.
      Left hydronephrosis and related back pain disappeared postoperatively. The number
      of patients with an indication of ileal-ureteral substitution is increasing for
      various disorders, and thus, the present report gives additional suggestions for
      the follow up of patients with ileal ureter.

PMID- 16448440
TI  - Intra-abdominal desmoid tumor following retroperitoneal lymph node dissection for
      testicular germ cell tumor.
AB  - In the testicular cancer post-treatment setting a rapidly growing retroperitoneal
      mass leads to a differential diagnosis including recurrent germ cell tumor,
      residual mature teratoma, or sarcomatoid degeneration. We report the case of a 27
      year-old man with a large abdominal mass occurring in the setting of a mixed germ
      cell tumor after radical orchiectomy with primary chemotherapy followed by
      retroperitoneal lymph node dissection. Surgical excision of this mass followed by
      pathological review revealed an intra-abdominal desmoid tumor. Fluorescence in
      situ hybridization (FISH) for isochromosome 12p failed to demonstrate a germ cell
      tumor origin. This is the fourth such case of an intra-abdominal desmoid tumor
      after retroperitoneal lymph node dissection for testicular cancer in the urologic
      literature. This case highlights the need for careful consideration of a desmoid
      tumor when a rapidly growing spindle cell tumor is encountered in a post
      treatment testis cancer patient.

PMID- 16448441
TI  - Discovery of a pituitary adenoma following treatment with a gonadotropin
      releasing hormone agonist in a patient with prostate cancer.
AB  - We report the case of a T3 prostate cancer in a 70-year-old white man. Hormone
      therapy represents a prominent branch in the treatment of locally advanced and
      metastatic prostate cancer. Gonadotropin-releasing hormone agonists have been
      proven to have a double effect on androgen metabolism: an initially stimulating,
      followed by an inhibitory, effect on the pituitary gland. This phenomenon may be
      noxious in the case of gonadotroph adenoma, with subsequent symptoms of
      intracranial hypertension. Gonadotropin-releasing hormone antagonists (abarelix),
      by avoiding the flare-up reaction, might be used in such instances.

PMID- 16448442
TI  - Partial androgen insensitivity syndrome with thermolability in the androgen
      receptor.
AB  - We report case of partial androgen insensitivity syndrome in a 12-year-old boy
      referred to our clinic complaining of bilateral gynecomastia and left undescended
      testicle. Laparoscopy for undescended testicle and bilateral mastectomy were
      performed, and the left testicle was absent. When skin fibroblasts of the scrotum
      obtained during surgery were cultured to analyse the androgen receptors, a slight
      thermolability was observed. Genomic examination of the androgen receptor gene
      could not detect any mutations.

PMID- 16448443
TI  - Delayed post-traumatic prostatic-urethrorectal fistula: transperineal rectal
      sparing repair - point of technique.
AB  - We describe the outcome and management of an unusual and interesting case of
      delayed post-traumatic prostatorectal fistula in a 40-year-old man. The fistula
      was repaired successfully via transperineal access without rectal or sphincteric
      transgression. We found the transperineal surgical approach simple, effective and
      useful in approaching the prostatorectal region for rectourinary fistulas. The
      transperineal approach is useful and should be considered in such select cases.
      We describe our technique that may be beneficial to many urologists.

PMID- 16448444
TI  - Huge epidermoid cyst of the spermatic cord in an adult patient.
AB  - Tumors arising in the spermatic cord are uncommon and form a heterogeneous group
      of neoplasms. A variety of both benign and malignant lesions have been
      demonstrated. Benign tumors represent 80% of the total, but unfortunately
      clinical and sonographic features are not specific and they cannot safely
      differentiate a teratomatous or a malignant neoplasm from benign tumors. We
      report a case of a huge epidermoid cyst of the spermatic cord in an adult patient
      confirmed after local excision. The etiology, differential diagnosis, and
      management alternatives are discussed.

PMID- 16448446
TI  - Introduction to chronic hepatitis B infection.
AB  - Chronic hepatitis B virus (HBV) infection affects over 350 million people
      worldwide and over 1 million die annually of HBV-related chronic liver disease.
      Although many individuals eventually achieve a state of nonreplicative infection,
      the prolonged immunologic response to infection leads to the development of
      cirrhosis, liver failure, or hepatocellular carcinoma (HCC) in up to 40% of
      patients. In endemic areas, where carrier rates are >5%, most individuals are
      infected perinatally, by vertical transmission, or in early childhood. In the
      United States, where prevalence is low except in particular areas and populations
      (e.g., Alaskan natives, immigrants from highly endemic areas), transmission is
      generally horizontal, percutaneous, or via sexual contact in adulthood. A variety
      of host (age at infection, gender, immune status); viral (viral load, genotype,
      mutation); and external (concurrent viral infections, alcohol consumption,
      chemotherapy) factors influence disease progression. Several variables (age at
      infection, gender, ethnicity, immune status) also influence the risk of chronic
      infection. Perinatal transmission, the most common mode of infection worldwide,
      can be reduced by appropriate prophylaxis (vaccination of the infant at birth
      together with hepatitis B immune globulin); anti-viral therapy in late pregnancy
      may also be beneficial. Five drugs are now FDA-approved for the treatment of HBV
      (interferon, lamivudine, adefovir, entecavir, and peginterferon alfa-2a), and
      suppressive anti-viral therapy improves the natural history of HBV. Patients with
      decompensated cirrhosis or HCC are highly likely to die unless they successfully
      undergo liver transplantation. While novel anti-viral drugs have improved the
      management of cirrhosis, strategies to prevent and treat HCC remain inadequate.

PMID- 16448448
TI  - Looking to the future: new agents for chronic hepatitis B.
AB  - New antiviral agents are currently being developed to treat patients with chronic
      hepatitis B. Both pegylated interferon alfa-2a and entecavir are now approved for
      the treatment of hepatitis B while telbivudine, tenofovir, emtricitabine, and
      pegylated interferon alfa-2b are in clinical development. Successive advances
      have resulted in more profound suppression of hepatitis B replication, a
      reduction in breakthrough resistance, and an increase in the frequency of
      attainment of virologic, serologic, biochemical, and histologic clinical
      endpoints.

PMID- 16448447
TI  - Therapeutic options for chronic hepatitis B: considerations and controversies.
AB  - Five agents are currently approved for the treatment of chronic hepatitis B
      infection. This article will discuss the three agents for which the most
      extensive data are available; interferon (IFN), lamivudine, and adefovir, while
      the following article by Dr. Jules Dienstag will discuss the recently marketed
      agents, entecavir and peginterferon alfa-2a. The advantages of IFN are its finite
      duration of therapy (4-6 months), lack of emergence of resistance, and durability
      of response. On the negative side, response to IFN is less durable in patients
      with HBeAg-negative chronic hepatitis B virus (HBV). Also, use of IFN is limited
      by adverse effects and the mode of administration (daily to thrice-weekly
      subcutaneous injection). Lamivudine and adefovir are orally administered and have
      good tolerability and safety. Even in patients who experience a marked decrease
      in serum HBV DNA and loss of HBeAg, oral therapy needs to be continued for at
      least 6 months, to avoid the risk of reappearance of HBeAg and viremia. Rates of
      HBeAg seroconversion to anti-HBe-positivity increase with duration of lamivudine
      or adefovir therapy. The likelihood of development of resistance to lamivudine
      and associated viral breakthrough limits its long-term use. In patients with
      HBeAg-negative chronic hepatitis B, long-term therapy is usually required, as off
      treatment relapse is common. The emergence of resistance to adefovir is delayed
      and infrequent, hence adefovir may be preferred in patients requiring long-term
      therapy.

PMID- 16448449
TI  - Optimizing management strategies in special patient populations.
AB  - Chronic hepatitis B infection presents a number of challenges to clinicians.
      There are additional considerations when defining management strategies for
      individuals with advanced liver disease, or coinfection, or those at high risk of
      developing hepatocellular carcinoma (HCC). Treatment of decompensated cirrhosis
      is particularly important. Evidence suggests that suppression of viral
      replication through nucleos(t)ide analog therapy leads to longer time to
      transplantation, improved liver function, and improved survival times. The use of
      interferon in patients with decompensated hepatitis B is associated with serious
      complications and is currently contraindicated for these patients by the AASLD
      Practice Guidelines. Hepatitis B coinfection is often associated with more
      extensive disease. In patients with HBV/HCV coinfection, one disease is usually
      dominant and consequently should be the focus of therapy. HIV/HBV coinfection
      increases the risk of progressive liver disease. Therapeutic agents active
      against both viruses should be utilized at the correct dose to limit the
      development of resistance. Agents specific for HBV, e.g., entecavir, enable
      hepatitis to be treated while avoiding the risk of HIV resistance developing.
      Dual infection with HBV and HDV is particularly challenging. Nucleos(t)ide
      analogs are ineffective in treating HDV infection, and there is limited data
      concerning the efficacy of interferon in this setting. The association between
      chronic hepatitis B infection and hepatocellular carcinoma (HCC) is well
      established. In patients at high risk of HCC, screening regimes may be effective.
      Furthermore, there is an increasing body of evidence indicating that effective
      suppression of viral replication may be associated with a reduced risk of HCC.

PMID- 16448450
TI  - Advancing patient care: integrating new data.
AB  - Physicians involved in the management of patients with chronic hepatitis B
      infection are frequently faced with complex clinical issues concerning the
      diagnosis, investigation, and treatment of patients. Guidelines exist within the
      literature that help with decision making; however, in practice individual
      nuances are often encountered necessitating decisions that go beyond the current
      guidelines. Following presentation of the available data, a panel of expert
      hepatologists and gastroenterologists sought to identify and solve challenges
      that are faced by clinicians in the daily management of patients with chronic
      hepatitis B infection. The following summary provides an overview of the outcome
      of these discussions. Because of the complexities of clinical management, the
      recommendations reflect the opinion of the majority; however, many
      recommendations were not unanimous. Furthermore, the recommendations that follow
      are limited to adult patients; the treatment of children was not discussed. A
      number of issues were identified, and statements concerning possible management
      strategies that could be applied were developed.

PMID- 16448451
TI  - Selecting appropriate management strategies for chronic hepatitis B: who to
      treat.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a significant problem. In the
      United States estimates indicate that 0.3% of the population (1.25 million
      individuals) have chronic hepatitis B infection. METHODS: Review of published
      practice guidelines and literature on management of hepatitis B to determine: 1)
      Which persons in Western populations are at the highest risk for HBV infection
      and should be screened for HBV seromarkers to identify those who are chronically
      infected and those who need to be protected with hepatitis B vaccine; 2) The
      importance of regular monitoring in persons with chronic hepatitis B, the
      frequency of monitoring, and which tests should be performed; 3) How to identify
      the patients who are appropriate candidates for antiviral therapy. RESULTS:
      Recommendations for screening, diagnosis, monitoring, and treatment of chronic
      HBV infection are reviewed. Important differences are discussed between the
      Practice Guidelines for chronic hepatitis B developed by the American Association
      for the Study of Liver Diseases (AASLD), the European Association for the Study
      of the Liver (EASL), and the Asian Pacific Association for the Study of the Liver
      (APASL). In addition, this article reviews which patients who are no covered by
      these Guidelines might be candidates for antiviral therapy. DISCUSSION:
      Established practice guidelines provide direction to providers for the diagnosis
      and management of chronic HBV infection to reduce the risk of serious sequelae.
      However, not all patients with chronic hepatitis B are identified, and many of
      those who are diagnosed do not receive adequate management and follow-up.

PMID- 16448452
TI  - Clinical model for distinguishing nonalcoholic steatohepatitis from simple
      steatosis in patients with nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) encompasses both simple steatosis and
      nonalcoholic steatohepatitis (NASH). Differentiation of these two entities
      requires histopathologic evaluation. The aim of this study was to establish a
      reliable diagnostic model for differentiating steatosis from steatohepatitis
      utilizing both clinical characteristics and a panel of biochemical markers of
      lipid peroxidation and fibrosis. Eighty subjects with biopsy proven NAFLD were
      enrolled, 39 with simple steatosis and 41 with histopathologic evidence of NASH.
      Demographic and laboratory data to include serologic testing for 8-epi
      PGF(2alpha), transforming growth factor-beta (TGF-beta), adiponectin, and
      hyaluronic acid (HA) were obtained and compared between the two groups. There
      were significant differences between the two groups with respect to age
      (P=0.004), female gender (P=0.024), aspartate aminotransferase (AST) (P=0.028),
      body mass index (BMI) (P=0.003), fasting insulin (0.018), AST/alanine
      aminotransferase (ALT) ratio (AAR) (P=0.017), quantitative insulin sensitivity
      check index (QUICKI) (P=0.002), and HA (P=0.029). A composite index for
      distinguishing steatosis from NASH was calculated by summing the risk factors of
      age >or=50 years, female gender, AST>or=45 IU/l, BMI >or=30 mg/kg2, AAR>or=0.80,
      and HA>or=55 microg/l, and its accuracy was determined by receiver operating
      characteristic (ROC) analysis to be 0.763 (95% CI: 0.650-0.876). The presence of
      three or more risk factors had a sensitivity, specificity, PPV, and NPV of 73.7%,
      65.7%, 68.2%, and 71.4%, respectively. In addition, HA at a cutoff of 45.3
      microg/l was a good predictor of advanced fibrosis. In conclusion, we propose a
      noninvasive screening model for distinguishing simple steatosis from NASH.
      Identifying patients at risk for NASH will allow clinicians to more accurately
      determine who may benefit from liver biopsy.

PMID- 16448453
TI  - Expression of oxidative stress-related molecules in circulating leukocytes and
      urine in patients with chronic viral hepatitis.
AB  - AIMS: Oxidative stress plays a role in pathogenesis of chronic viral hepatitis.
      Expression of oxidative stress-related molecules remains to be clarified.
      METHODS: 4-hydroxy-2-nonenal (4-HNE), 4-hydroxy-2-hexenal (4-HHE), catalase,
      superoxide dismutase-1 (SOD-1), glutathione peroxidase-1, thioredoxin (TRX) in
      leukocytes and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined in 164
      persons, including 130 chronic viral hepatitis patients and 34 normal
      individuals, by Western blot analysis and enzyme-linked immunosorbent assay,
      respectively. Hepatic expression of these proteins was immunohistochemically
      examined in 12 patients with chronic viral hepatitis, compared with three persons
      without liver damage. RESULTS: The 4-HNE/beta-actin ratios in chronic viral
      hepatitis were significantly higher than those in normal individuals (P<0.01),
      and were significantly correlated with asparate aminotransferase (AST) and
      alanine aminotransferase (ALT) (P<0.01, each). The catalase/beta-actin and SOD
      1/beta-actin ratios in chronic viral hepatitis were higher than those in normal
      individuals, and were significantly correlated with 4-HNE/beta-actin ratios
      (P<0.01, each). Hepatic expression of 4-HNE, 4-HHE, catalase, SOD-1 and TRX in
      chronic viral hepatitis was higher than that without liver damage. Urinary
      excretion of 8-OHdG was not changed in chronic viral hepatitis. CONCLUSIONS: The
      results of the present study suggest that expression of oxidative stress-related
      molecules in leukocytes is upregulated in relation to serum aminotransferase
      levels.

PMID- 16448454
TI  - Effects of fatty liver and related factors on the efficacy of combination
      antiviral therapy in patients with chronic hepatitis C.
AB  - OBJECTIVE: Hepatic steatosis is a histological feature in patients with chronic
      hepatitis C (CHC) and adversely affects the virologic response rates to anti
      hepatitis C virus (HCV) therapy. The aim of this study is to investigate whether
      the fatty liver and related factors have impact on the efficacy in CHC treated
      with peginterferon and ribavirin, and the associations between HCV genotyping and
      fatty liver. METHODS: Ninety-eight patients received subcutaneously 180 mug
      peginterferon alpha-2a once a week plus ribavirin. HCV genotypes and the levels
      of plasma insulin of patients were measured. Fatty liver was detected by B
      ultrasound. The body mass index (BMI), waist-to-hip ratio (WHR) and homeostasis
      model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS: Among
      98 CHC patients, 38 (38.8%) were infected with genotype 1; 44 (44.9%) with
      genotype 2; 13 (13.3%) with genotype 3; 3 (3.0%) with indeterminate genotype. The
      prevalence of fatty liver was 10.5%, 11.4%, 38.5% in patients infected with HCV
      genotype 1, 2, 3, respectively, which suggested that the distribution of fatty
      liver in different HCV genotypes was imbalanced (chi2=6.758, P=0.034). In
      univariate analysis, the efficacy of combination therapy was significantly
      associated with BMI (P=0.011), WHR (P=0.024), the levels of plasma insulin
      (P=0.001), genotype (P=0.036), presence of fatty liver (P=0.028), treatment
      dosage and duration (P=0.012) and HOMA-IR (P=0.002). With binary logistic
      regression analysis, the plasma insulin levels and HOMA-IR showed independent
      predictors to the efficacy of antiviral therapy. CONCLUSION: The prevalence of
      fatty liver in HCV genotype 3 was markedly higher than that of other genotypes.
      The BMI, WHR, the levels of plasma insulin, genotype, presence of fatty liver,
      treatment dosage and duration and HOMA-IR were associated with the sustained
      virologic response. The level of plasma insulin and HOMA-IR were independent
      factors for predicting effect of antiviral therapy.

PMID- 16448455
TI  - Clinical and prognostic role of plasma coagulation factor XIII activity for
      bleeding disorders and 6-year survival in patients with chronic liver disease.
AB  - BACKGROUND/AIMS: Alterations of plasma coagulation factor XIII may contribute to
      bleeding disorders in patients with liver cirrhosis. As standard clotting tests
      such as prothrombin time or activated thromboplastin time (aPTT) cannot detect
      factor XIII deficiency, this may often be overlooked in clinical practice. We
      aimed to define factor XIII's clinical and prognostic role in chronic liver
      disease. PATIENTS AND METHODS: Factor XIII activities were assessed among various
      other parameters in 111 patients with chronic liver diseases during evaluation
      for liver transplantation in a prospective study. RESULTS: Unlike coagulation
      factors II, V or VII, factor XIII activity was maintained in the majority of
      patients with liver cirrhosis. However, although rarely, factor XIII deficiencies
      (<50%) occurred, especially in Child C cirrhosis. Factor XIII levels correlated
      with liver's biosynthetic capacity (cholinesterase activity, albumin, total
      protein) as well as with platelet count, global coagulation tests and other
      single coagulation factors. Patients reporting a current systemic bleeding
      tendency at study entry had significantly reduced factor XIII. In a 6-year follow
      up, patients with factor XIII<50% had a significantly increased risk of severe
      upper gastrointestinal bleed, and reduced factor XIII (<50%, 50-75% vs. normal)
      was associated with increased mortality. CONCLUSIONS: Factor XIII deficiency is
      rare in patients with liver cirrhosis, but is associated with a clinical bleeding
      tendency and an unfavorable prognosis for future hemorrhages and survival.

PMID- 16448456
TI  - Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily
      dose consumption.
AB  - Hypervitaminosis A-related liver toxicity may be severe and may even lead to
      cirrhosis. In the normal liver, vitamin A is stored in hepatic stellate cells
      (HSC), which are prone to becoming activated and acquiring a myofibroblast-like
      phenotype, producing large amounts of extracellular matrix. AIMS: In order to
      assess the relationship between vitamin A intake, HSC activation and fibrosis, we
      studied nine liver biopsies from patients belonging to a well-characterized
      series of 41 patients with vitamin A hepatotoxicity. METHODS: Fibrosis was
      underlined by Sirius-red staining, whereas activated HSC were
      immunohistochemically identified using an antibody against alpha smooth muscle
      actin. The volume density (Vv) of sinusoidal and total fibrosis and of sinusoidal
      and total activated HSC was quantified by the point-counting method. RESULTS:
      Morphology ranged from HSC hypertrophy and hyperplasia as the sole features to
      severe architectural distortion. There was a significant positive correlation
      between Vv of perisinusoidal fibrosis and the daily consumption of vitamin A
      (P=0.004). CONCLUSION: The close correlation between the severity of
      perisinusoidal fibrosis and the daily dose of the retinol intake suggests the
      existence of a dose-effect relationship.

PMID- 16448457
TI  - The relationship between hepatic immunoglobulin production and CD154 expression
      in chronic liver diseases.
AB  - BACKGROUND: CD40-CD154 is a receptor-ligand pair that provides key communication
      signals between cells of the adaptive immune system in states of inflammation and
      autoimmunity. The CD40 receptor is expressed constitutively on B lymphocytes, for
      which it provides important signals regulating clonal expansion and antibody
      production. CD154 is a member of the tumor necrosis factor superfamily, which is
      primarily expressed by activated T cells. METHODS: Because many chronic liver
      diseases are characterized by lymphocytic infiltration of the liver and several
      have increased immunoglobulin (Ig) production, the role of CD40-CD154 in hepatic
      Ig production was investigated in patients with primary biliary cirrhosis (PBC),
      primary sclerosing cholangitis, autoimmune hepatitis (AIH), hepatitis C,
      hepatitis B, alcoholic and non-alcoholic steatohepatitis, as well as normal
      controls. RESULTS: Soluble CD154 levels in the serum were found to be no
      different in chronic liver diseases vs normal controls. Likewise, CD154 mRNA
      levels in peripheral blood mononuclear cells did not differ. However, mRNA for
      CD154 was significantly increased in the liver of individuals with PBC and AIH as
      compared with the other groups. The quantity of CD154 mRNA in the liver
      correlated positively with the quantity of mRNA for secretory Ig. CONCLUSION:
      These findings suggest that CD40-CD154 signals may be involved in Ig production
      within the liver of autoimmune liver diseases.

PMID- 16448458
TI  - Reduced heart rate variability and baroreflex sensitivity in primary biliary
      cirrhosis.
AB  - BACKGROUND: Standardized mortality ratio for primary biliary cirrhosis (PBC) is
      2.87. Even after accounting for liver and cancer-related deaths there is an
      unexplained excess mortality associated with PBC. We have assessed heart rate
      variability (HRV) and baroreflex sensitivity (BRS) risk factors associated with
      cardiovascular mortality, in 57 PBC patients and age- and sex-matched normal
      controls. METHODS: HRV and BRS were measured non-invasively in subjects and
      controls. Beat to beat RR interval and 'Portapres' blood pressure data were
      processed using power spectral analysis. Power was calculated in very low
      frequency (VLF), low-frequency (LF) and high-frequency (HF) bands according to
      international guidelines. BRS (alpha) was computed using cross-spectrum analysis.
      Patients also underwent fatigue severity assessment using a measure validated for
      use in PBC. RESULTS: PBC patients had significantly lower total HRV compared with
      controls (P=0.02), with the reduction occurring predominantly in the LF domain
      (P=0.03). BRS was also significantly reduced compared with controls (P=0.02).
      There were no significant differences in HRV or BRS between cirrhotic and non
      cirrhotic patients. Within the PBC patient group HRV was significantly lower in
      fatigued than in non-fatigued patients (P<0.05). CONCLUSION: Abnormalities of HRV
      and BRS in PBC are not specific to advanced disease but are associated with
      fatigue severity. Abnormalities could be associated with increased risk of sudden
      cardiac death, potentially contributing to the excess mortality seen in PBC.

PMID- 16448459
TI  - Serum lipid and lipoprotein alterations represent recovery of liver function
      after hepatectomy.
AB  - BACKGROUND: The assessment of liver function during human liver regeneration is
      necessary to prevent unexpected liver failure and to prepare for further
      treatment. We selected patients prospectively and measured serum lipid and
      lipoprotein levels to identify which lipids and lipoproteins could represent
      recovery of liver function in human liver regeneration. METHODS: Thirty selected
      patients who underwent hepatectomy were divided into three groups depending on
      the serum hyaluronate (HA) level and the type of liver resection. RESULTS: We
      found three patterns of lipid and lipoprotein alterations after hepatectomy.
      Among the lipids and lipoproteins examined, the serum beta-lipoprotein and low
      density lipoprotein (LDL) levels were significantly different among the groups at
      7 days after hepatectomy. The alteration of the apolipoprotein (Apo) B level was
      similar to that of LDL. The LDL level was correlated with both beta-lipoprotein
      and Apo B before hepatectomy (r=0.653 and 0.894, respectively) and at 7 days
      after hepatectomy (r=0.841 and 0.943, respectively). CONCLUSION: Serum HA before
      hepatectomy can reflect postoperative liver function depending on the type of
      liver resection. Recovery of the beta-lipoprotein and LDL levels can reflect the
      recovery of liver function in human liver regeneration within the early period in
      association with the Apo B level.

PMID- 16448460
TI  - Transthyretin RNA profiling in livers from transplanted patients affected by
      familial amyloidotic polyneuropathy, and identification of a dual transcription
      start point.
AB  - Mutations in the transthyretin (TTR) gene cause familial amyloidotic
      polyneuropathy (FAP), an autosomal dominant peripheral neuropathy, often
      associated with cardiomyopathy. Liver transplant currently represents a powerful
      therapeutic approach for FAP patients, although its efficacy is heavily dependent
      both on the disease severity and on the cardiac functionality. We have
      investigated the TTR gene expression searching for tissue-specific additional
      messengers in human adult and foetal tissues as well as in eight livers from FAP
      transplanted patients carrying different TTR mutations (Met30, Pro36, Ala47,
      Arg50, and Gln89). We identified a novel transcript, recognising a different
      transcription start site. The additional 5'-UTR sequence of this novel transcript
      contains regulatory boxes possibly highlighting an additional transcription start
      point. RNA analysis revealed that this region is represented in all foetal/adult
      tissues analysed. We discussed the implications of this finding which might
      provide perspectives for better understanding the TTR gene expression.

PMID- 16448461
TI  - DLPC and SAMe combined prevent leptin-stimulated TIMP-1 production in LX-2 human
      hepatic stellate cells by inhibiting HO-mediated signal transduction.
AB  - BACKGROUND/AIMS: Both dilinoleoylphosphatidylcholine (DLPC) and S
      adenosylmethionine (SAMe) have antioxidant properties and antifibrogenic actions.
      Because H2O2 mediates signal transduction-stimulating liver fibrogenesis, we
      investigated whether DLPC and SAMe attenuate the production of tissue inhibitor
      of metalloproteinase (TIMP)-1 by inhibiting H2O2 formation. METHODS: LX-2 human
      hepatic stellate cells were treated with leptin with or without DLPC, SAMe or
      various inhibitors. RESULTS: Leptin-stimulated TIMP-1 mRNA and its protein were
      diminished by DLPC or SAMe alone, and the response was fully prevented by the
      combination of DLPC and SAMe. H2O2 was increased while glutathione was decreased;
      these changes were prevented by AG490, suggesting a Janus kinases (JAK)-mediated
      process. Up-regulation of leptin receptor and activation of JAK1 and 2 were not
      affected by DLPC+SAMe, whereas phosphorylation of ERK1/2 and p38 was blocked by
      DLPC+SAMe or catalase, suggesting an H2O2-dependent mechanism. These treatments
      also suppressed leptin-stimulated TIMP-1 promoter activity and decreased TIMP-1
      mRNA stability, contributing to TIMP-1 mRNA down-regulation. PD098059, an ERK1/2
      inhibitor, suppressed TIMP-1 promoter activity, whereas SB203580, a p38
      inhibitor, decreased TIMP-1 message stability; both resulted in a partial
      reduction of TIMP-1 mRNA. CONCLUSION: As decreased TIMP-1 production may enhance
      collagen deposition, the combined administration of DLPC+SAMe should be
      considered for the prevention of H2O2-mediated signaling and the resulting
      fibrosis.

PMID- 16448462
TI  - Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers.
AB  - BACKGROUND: Liver fibrosis is the common response to chronic liver injury,
      ultimately leading to cirrhosis. Several lines of evidence indicate that inducing
      apoptosis of hepatic stellate cells (HSC) may lead to regression of liver
      fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC.
      However, the clinical use of GTX may be limited because of the lack of cell and
      tissue specificity, causing a high risk of potentially severe adverse effects.
      The aim of this study, therefore, was to study the effect of GTX on different
      cells of the liver. METHODS: We used normal and fibrotic precision-cut rat liver
      slices to study the effect of GTX on the various resident liver cell types. In
      these slices, the complex cell-cell interactions are preserved, which closely
      mimics the in vivo situation. RESULTS: GTX exhibited a potent apoptosis-inducing
      activity in these slices. Both immunohistochemical stainings and real-time mRNA
      techniques showed that this apoptosis-inducing effect was seen in HSC. However,
      Kupffer cells and liver endothelial cells were also affected by GTX, whereas
      hepatocytes were only mildly affected. CONCLUSIONS: This study indicates that the
      apoptosis-inducing strategy to treat liver fibrosis has high potential, but it
      will be necessary to develop an HSC-specific therapy to prevent adverse effects.

PMID- 16448464
TI  - Effect of hyperbaric oxygen on cold storage of the liver in rats.
AB  - BACKGROUND: The depletion of biochemical energy stores during prolonged cold
      storage is one of the most critical events of cold ischemia-reperfusion (CI/R)
      injury. The aim of this study was to evaluate the effect of hyperbaric oxygen
      (HBO) treatment on CI/R injury. METHODS: Livers were harvested from male Wistar
      rats and stored for 24 h at 4 degrees C in University of Wisconsin solution
      (Group 1). Others were additionally treated with HBO during the preservation
      period (Group 2). At the end of the 24 h cold preservation, the concentrations of
      hepatic enzymes and lipid peroxidation (LPO) in the effluent and the hepatic
      adenosine triphosphate (ATP) levels were measured. After preservation, the livers
      were reperfused for 90 min with an oxygenated Krebs-Henseleit bicarbonate buffer.
      Perfusate samples were obtained serially, and portal flow rates were also
      recorded. RESULTS: In group 2, aspartate aminotransferase (AST), lactate
      dehydrogenase (LDH), and LPO into the effluent at the end of preservation were
      decreased and the depletion of ATP was prevented (P<0.05). After reperfusion, the
      portal flow was significantly improved in group 2 (P<0.05). The time-dependent
      increase of alanine aminotransferase levels (ALT) observed in group 1 was
      suppressed significantly in group 2, and total bile production during 90 min of
      reperfusion was significantly greater in group 2 (P<0.05). The structure of the
      livers in group 2 was significantly well maintained, and the liver weight change
      ratio was significantly greater in group 1 (P<0.05). CONCLUSIONS: HBO treatment
      during cold storage seems to prevent hepatic ischemic injury and have protective
      effects against CI/R injury by attenuating the depletion of energy stores.

PMID- 16448463
TI  - The role of p28GANK in rat oval cells activation and proliferation.
AB  - BACKGROUND: Human gankyrin gene product (p28GANK) is a novel oncogenic protein
      ubiquitously overexpressed in hepatocellular carcinoma and also plays a role in
      cell cycle progression in normal hepatocytes and liver regeneration. However,
      little is known about the physiological role of p28GANK in the liver oval cell
      activation and proliferation. We investigated the possible involvement of p28GANK
      in oval cell-mediated liver regeneration and cell cycle progression. METHODS: We
      examined the different p28GANK expression in 2-acetylaminofuorene/partial
      heptectomy (2-AAF/PH) rats, as a model of oval cell activation, and PH rats by
      Western blot and immunohistochemistry. Oval cells isolated from 2-AAF/PH rat
      model were cultured in our study. p28GANK expression was examined in the oval
      cells after mitogenic stimulation. RESULTS: In 2-AAF/PH rats, p28GANK was
      expressed in the activated oval cells and located in the nucleus. p28GANK protein
      expression was increased in 2-AFF/PH rats after hepatectomy lasting for 96 h when
      retinoblastoma maintained hyperphosphorylation status at Ser-795. The isolated
      oval cells express AFP, OV6, CK19, CD34, CD45, c-kit and albumin. After epidermal
      growth factor stimulation, p28GANK protein was up-regulated in oval cells from 24
      to 72 h, which coincided with increased expression of CyclinD1, CDK4 and
      decreased of Rb protein. CONCLUSIONS: p28GANK expression was increased in oval
      cell-mediated liver regeneration and oval cells after mitogenic stimulation.
      Thus, p28GANK may play a role in oval cell-mediated liver regeneration and liver
      oval cell cycle progression.

PMID- 16448465
TI  - Splenic artery ligation ameliorates hepatic ischemia and reperfusion injury in
      rats.
AB  - BACKGROUND/AIMS: Hepatic injury caused by ischemia/reperfusion (I/R) is a key
      clinical problem associated with liver transplantation and liver surgery. The
      spleen is involved in hepatic I/R injury. In this study, we examined the effects
      of splenic artery ligation on hepatic I/R injury. METHODS: Splenic artery
      ligation was performed 7 days, 3 days, or just before the hepatic ischemia.
      Hepatic ischemia was conducted by occluding the blood vessels to the median and
      left lateral lobes with an atraumatic vascular clamp. Hepatic I/R injury was
      induced by 45 min of ischemia followed by 120 min of reperfusion. RESULTS: When
      splenic artery ligation was performed at 3 days or just before the ischemia,
      serum aspartate transaminase and alanine transaminase activities, as markers for
      hepatic injury, decreased as compared with the rats with I/R alone. Splenic
      artery ligation also reduced the myeloperoxidase activity, an enzyme present in
      neutrophils, and the expression of interleukin-6 mRNA, a proinflammatory
      cytokine, in rat livers with I/R. Efficacy of splenic artery ligation on hepatic
      I/R injury was also confirmed by histology. On the other hand, when splenic
      artery ligation was conducted 7 days before the ischemia, efficacy of splenic
      artery ligation was disappeared. CONCLUSIONS: Splenic artery ligation ameliorates
      hepatic I/R injury in rats. These results strongly suggest the clinical
      usefulness of this surgical procedure to protect the liver against I/R injury.

PMID- 16448466
TI  - Rat liver fibrosis regresses better with pegylated interferon alpha2b and
      ursodeoxycholic acid treatments than spontaneous recovery.
AB  - BACKGROUND/AIMS: Fibrosis and cirrhosis are common complications of chronic liver
      diseases. An imbalance between fibrogenesis and fibrolysis results in scarring of
      the liver parenchyma. We aimed to investigate the possible antifibrotic
      effectiveness of a newly modified interferon molecule peginterferon alpha2b (PEG
      IFNalpha2b) which has better antiviral activity, and ursodeoxycholic acid (UDCA).
      METHODOLOGY: Liver fibrosis was established on 60 male Sprague Dawley rats with
      CCl4 in 12 weeks. After cessation of CCl4 Group I was left for spontaneous
      recovery. Group II was treated with PEG-IFN 1.5 microg/kg/week, Group III with
      UDCA 25 mg/kg/day and Group IV with combination of both drugs. All rats were
      killed at week 16. Histopathologic fibrosis scores, tissue hydroxyproline, TIMP-1
      and MMP-13 levels were determined. Hepatic stellate cell apoptosis was detected
      by dual staining with TUNEL technique and anti-alpha smooth muscle actin.
      RESULTS: Fibrosis scores were lower in Group II, III and IV than Group I (p<0.05
      for group I vs. II and III; p<0.01 for group I vs. IV). Tissue hydroxyproline
      levels were significantly decreased in Group II, III and IV when compared to
      Group I (p<0.05 for group I vs. II, p<0.01 for group I vs. III and IV). Lower
      liver TIMP-1 and higher MMP-13 levels were measured in Group II, III, and Group
      IV than Group I (p<0.01 for TIMP-1 and p<0.01, for MMP). Activated HSC apoptosis
      was significantly increased in Group II, III and IV when compared to Group I
      (p<0.01, for all). There was significantly higher apoptosis in Group II than
      Group III and IV (p<0.01). CONCLUSION: Treatment with both PEG-IFNalpha2b and
      UDCA improved CCl4 induced rat liver fibrosis. Significantly higher effects were
      obtained using these agents in combination.

PMID- 16448467
TI  - MTHFR C677T mutations in liver cirrhosis with and without portal vein thrombosis.

PMID- 16448468
TI  - Helping to create the evidence base.

PMID- 16448469
TI  - An audit of diabetes control, dietary management and quality of life in adults
      with type 1 diabetes mellitus, and a comparison with nondiabetic subjects.
AB  - OBJECTIVES: The study's objective was to audit current diet and disease
      management in a community-based sample of people with type 1 diabetes. METHODS:
      The study involved adults with type 1 diabetes and control subjects. Reported
      amounts of dietary intake were collected. Indices of diabetes control were
      determined by standard methods. Quality of life of both groups was assessed with
      appropriate measures. Results were compared between two groups. RESULTS: Mean
      HbA(1c) concentration was 8.5% (SD 2.21%) for women with diabetes and 8.6% (SD
      1.91%) for men. There was no significant difference between the diabetic and
      control subjects in self-reported energy intake and macronutrient intake, with
      the exception that the contribution of saturated fatty acid to energy intake was
      higher in male controls than in male diabetics. There was no association between
      dietary intakes and glycemic control in diabetic subjects. Anthropometric
      measurements, blood pressure and plasma lipids in patients were within normal
      range and not significantly different from the controls. Plasma fibrinogen
      concentration was higher in patients. Diabetic subjects did not have a diminished
      quality of life. CONCLUSIONS: Dietary management in these patients was generally
      focused on controlling carbohydrate intake. Most had suboptimal diabetes control.

PMID- 16448470
TI  - Frequency of under- and overfeeding in mechanically ventilated ICU patients:
      causes and possible consequences.
AB  - INTRODUCTION: In critically ill patients enteral nutrition (EN) is frequently
      associated with underfeeding and intolerance, whilst parenteral nutrition (PN)
      has been associated with a greater risk of infectious complications and
      overfeeding. MATERIALS AND METHODS: The adequacy of nutritional support provided
      to critically ill patients was prospectively recorded and compared with estimated
      requirements. The incidence of, and practices contributing to, under- (<80% of
      energy requirements) and overfeeding (>110% of energy requirements) were
      identified. RESULTS: Overall patients received approximately 81% and 76% of
      prescribed energy and protein intakes respectively. Underfeeding occurred on
      50.3% of days. Reasons for patients failing to achieve adequate intakes included,
      fasting for airway management procedures (21%) and gastrointestinal intolerance
      (14%). Overfeeding, although less common (18.6% of days), was more likely to
      occur in patients with a tracheostomy requiring prolonged mechanical ventilation
      (>16 days). The combination of oral and nasogastric feeding or use of nutrient
      dense feeds were most frequently associated with overfeeding. Discussion The
      overall adequacy of nutritional intakes in the present study was similar to those
      reported elsewhere. However, the incidence of overfeeding was greater than
      anticipated and occurred in patients already experiencing delayed weaning from
      mechanical ventilation.

PMID- 16448471
TI  - Eating together is important: using a dining room in an acute elderly medical
      ward increases energy intake.
AB  - AIM: To investigate the effect of eating in a supervised dining room, on
      nutritional intake and weight, for elderly patients on an acute medicine for the
      elderly ward. METHOD: Patients on the intervention ward were encouraged to attend
      a dining room every lunch time by a trained nursing assistant as part of the
      rehabilitation process. The patients on the control ward ate only by their
      bedside. Food intake and weight data were collected over the study period on each
      patient. RESULTS: Forty-eight patients participated in the study. At the lunch
      time meal studied the dining room group had higher intakes of energy compared
      with the controls [489 kcal (95% CI: 438-554) versus 360 kcal (95% CI: 289-448),
      P < 0.013]. There was no difference in protein intake between the groups [18.9 g
      (95% CI: 16.6-21.2) versus 17.7 g (95% CI: 13.2-22.2), P=0.63]. No significant
      difference in weight gain between the two groups was seen (P=0.6). However, there
      was a trend towards weight gain in the dining room group. CONCLUSION: Food intake
      can be improved by using a supervised dining room, and this will potentially lead
      to weight gain and corresponding improvements in nutritional status and
      rehabilitation.

PMID- 16448472
TI  - Home enteral feeding audit 1 year post-initiation.
AB  - OBJECTIVE To determine the practical problems that families of children on home
      enteral tube feeds (HETF) experience in the first year post-hospital discharge.
      METHODS Thirty parents/carers of children (0-16 years) completed a multiple
      choice/short answer questionnaire by interview 12 months after discharge from
      hospital. Issues addressed included: home delivery of feed and equipment; pump
      usage; tube changes; and overnight feeding. RESULTS: The main problems identified
      were: sleep disturbance (75%); frequent tube dislodgement (46%); tube blockages
      (41%); inability of some home delivery companies (HDC) to provide all the
      paediatric special feeds required (43%); and pump inaccuracy (23%). Conclusions
      Children on long-term HETF and their families experience significant problems
      with sleep disturbance, tube dislodgement and tube blockage. In addition,
      accuracy of pumps and obtaining feed and equipment was a source of stress.
      Dietitians and community nurses urgently need to explore solutions to the common
      problems associated with overnight feeding. Furthermore, regular home reviews are
      necessary in long-term HETF to continue to identify and minimize problems.

PMID- 16448473
TI  - Trends in energy and macronutrient intakes in non-under-reporters vary with the
      method used to identify under-reporters.
AB  - OBJECTIVE: To investigate effects of using different methods to identify under
      reporters on trends in dietary intake and physical activity level (PAL) in non
      under-reporters. DESIGN: Dietary intake and activity pattern were recorded by 887
      female university students from 1988 to 2003. Energy expenditure (EE) and PAL
      were measured using a factorial method. Nine methods were used to identify under
      reporters. Trends between 1988 and 2003 were determined from linear regression of
      median data for each year. RESULTS: Prevalence of under-reporting varied with the
      method used, ranging from 22.2% to 66.7%. Trends that were consistent using all
      methods were a decrease in per cent of energy from fat and no change in alcohol
      intake or PAL (P<0.05). Trends in energy and macronutrient intakes varied with
      the method used. Using the four methods that excluded the most under-reporters
      there were increases in energy and gram carbohydrate (CHO) intakes (P<0.05), but
      no change in gram fat intake. Using the four methods that excluded the fewest
      under-reporters there was no change in energy or gram CHO intake, but a decrease
      in gram fat intake (P<0.05). CONCLUSION: Trends in energy, fat and CHO intakes in
      non-under-reporters varied with the method used to identify under-reporters.

PMID- 16448474
TI  - The impact of a gluten-free diet on adults with coeliac disease: results of a
      national survey.
AB  - OBJECTIVE We sought to evaluate the impact of the gluten-free diet on the 5,240
      members of the Canadian Celiac Association (CCA). Data are presented on 2,681
      adults (>or=16 years) with biopsy-proven celiac disease (CD). METHODS: A mail-out
      survey was used. Quality of life was evaluated using the 'SF12', and celiac
      specific questions. RESULTS: Mean age was 56 years, mean age at diagnosis was 45
      years, and 75% were female. The 'SF12' summary scores were similar to normative
      Canadian data, but were significantly lower for females and newly diagnosed
      patients. Respondents reported: following a gluten-free (GF) diet (90%),
      improvement on the diet (83%), and difficulties following the diet (44%), which
      included: determining if foods were GF (85%), finding GF foods in stores (83%),
      avoiding restaurants (79%), and avoiding travel (38%). Most common reactions to
      consumed gluten (among 73%) included pain, diarrhea, bloating, fatigue, nausea,
      and headache. Excellent information on CD and its treatment was provided by the
      CCA (64%), gastroenterologists (28%), dietitians (26%) and family doctor (12%).
      CONCLUSIONS: Quality of life in those with CD could be increased with early
      diagnosis, increased availability of gluten-free foods, improved food labelling,
      and better dietary instruction. Education of physicians and dietitians about CD
      and its treatment is essential.

PMID- 16448475
TI  - Growth during the first 6 months of life in infants using formula enriched with
      Lactobacillus rhamnosus GG: double-blind, randomized trial.
AB  - BACKGROUND: Probiotic bacteria have beneficial effects on the immune system and
      gastrointestinal tract, but the impacts of their long-term consumption on health
      and growth in early infancy are not well documented. The aim of this study was to
      evaluate the influence of Lactobacillus rhamnosus GG (LGG)-enriched formula on
      growth and faecal microflora during the first 6 months of life in normal healthy
      infants. MATERIALS AND METHODS: One hundred and twenty healthy infants (up to 2
      months) received LGG-supplemented formula or regular formula in a double-blind,
      randomized manner until the age of 6 months. Weight, length and head
      circumference were measured monthly and transformed into standard deviation
      scores (SDS). Faecal samples were obtained from a random sample of infants (n=25)
      at entry and at the end of the study. RESULTS: One hundred and five infants (51
      in the LGG group) completed the study. Children receiving LGG-supplemented
      formula grew better: their changes in their length and weight SDS (DeltaSDS) at
      the end of the study were significantly higher than those receiving regular
      formula (0.44+/- 0.37 versus 0.07+/- 0.06, P< 0.01 and 0.44+/- 0.19 versus 0.07+/
      0.06, P< 0.005, respectively). The LGG group had a significant, higher
      defecation frequency 9.1+/-2.06 versus 8.0+/- 2.8 (P<0.05). More frequent
      colonization with lactobacilli was found in the LGG group, 91% versus 76%
      (P<0.05) at the end of the study. CONCLUSIONS Infants fed with LGG-enriched
      formula grew better than those fed with regular formula. Further studies are
      necessary to clarify the mechanism of LGG in infant growth.

PMID- 16448476
TI  - Identification of nutritionally adequate mixtures of vegetable oils by linear
      programming.
AB  - OBJECTIVE: To determine the types and proportions of vegetable oils to recommend
      for a healthy diet. METHODS: Optimal vegetable oil combinations were designed,
      using linear programming and, as decision variables, nine single oils and 29
      basic food items. 'Oil models' were run to determine whether reasonable amounts
      of individuals oils or oil mixtures satisfied a set of constraints on essential
      fatty acids and vitamin E. 'Meal models' were run to test whether selected
      mixtures could be used as the sole source of added fat in a meal that met
      micronutrient and macronutrient recommendations. RESULTS: The cheapest mixture
      (0.97 euro L(-1)) that solved the oil models contained 81% rapeseed and 19%
      sunflower oils. About 10-15 g of this mixture, alone or with olive, soya bean,
      wheat germ or walnut oils, also solved the meal models. Mixtures that contained a
      high proportion (>or=50%) of the tasty olive and walnut oils also solved the
      models but were more expensive (4.9 euro L(-1) and 8.5 euro L(-1), respectively).
      CONCLUSIONS: The consumption of a mixture composed of rapeseed and sunflower oils
      in a 4 : 1 proportion is an inexpensive and simple way to meet current dietary
      recommendations for essential fatty acids and vitamin E, favouring overall
      dietary nutrient adequacy.

PMID- 16448481
TI  - Family physician/nurse practitioner: stories of collaboration.
AB  - AIMS: This paper presents the experiences of nurse practitioners and family
      physicians working in collaborative practice at four Canadian rural primary care
      agencies. It focuses on the qualitative segment of a larger study examining the
      impact of an educational intervention on interprofessional practice. BACKGROUND:
      Growing awareness of the importance of health promotion and disease prevention,
      the increased complexity of community-based care, and the need to use scarce
      human healthcare resources, especially family physicians, far more efficiently
      and effectively, have resulted in increased emphasis on primary healthcare
      renewal in Canada. Key to primary healthcare renewal is care delivery through
      interdisciplinary teams that include nurse practitioners. METHODS: Narrative
      analysis, a form of interpretive analysis that respects the integrity of the
      stories told by participants, was chosen as the strategy to examine the narrative
      data gathered in two sets of interviews with the nurse practitioners and family
      physicians. The study was undertaken during 2000. RESULTS: Thirteen family
      physicians and five nurse practitioners with diverse educational backgrounds and
      varied experience with collaboration participated in the qualitative component of
      the study. A number of issues related to working in a shared practice were
      identified in nurse practitioner and family physician interviews across the
      research sites. The themes identified in participants' stories included issues
      related to the scope of practice, emphasizing the importance of role clarity and
      trust, the ideological difference regarding disease prevention and health
      promotion, differences in perceptions about the operation of collaborative
      practice, and the understanding that collaborative relationships evolve.
      CONCLUSIONS: The placement of nurse practitioners and family physicians in a
      common clinical practice without some form of orientation process does not
      produce collaborative practice. Educational strategies related to role
      expectations are necessary to facilitate the development of care delivery
      partnerships characterized by interdependent practice.

PMID- 16448482
TI  - Stress and well-being among parents of children with rare diseases: a prospective
      intervention study.
AB  - AIM: This paper reports a study to assess stress, well-being and supportive
      resources experienced by mothers and fathers of children with rare disabilities,
      and how these variables were affected by an intensive family competence
      intervention. BACKGROUND: Despite diagnosis-specific studies, little overall
      knowledge exists about life-consequences for families of children with rare
      disorders. METHOD: We used a prospective design with baseline data and two follow
      ups (at 6 and 12 months) after an intervention. The intervention aimed at
      empowering parents in managing their child's disability. Parents from all parts
      of Sweden visiting a national centre for families of children with rare
      disabilities were consecutively selected (n = 136 mothers, 108 fathers).
      Instruments of parental stress, social support, self-rated health, optimism and
      life satisfaction and perceived physical or psychological strain were used.
      Stratified analyses were carried out for mothers and fathers, and related to
      parental demands: single mothers, full-time employment, participation in a parent
      association, child's age and type of disability. RESULTS: We found high parental
      stress, physical and emotional strain among mothers, especially among single
      mothers. Fathers showed high stress related to incompetence, which decreased
      after the intervention. Decreased strain was found among full-time working
      mothers and fathers after the intervention. Parents' perceived knowledge and
      active coping and mothers' perceived social support were increased at follow-up.
      Factors related to parents' overall life satisfaction (57-70% explained variance)
      changed after the intervention, from being more related to internal demands
      (perceived strain, incompetence and social isolation) to other conditions, such
      as problems related to spouse, paid work and social network. CONCLUSION: Parents,
      especially fathers and full-time working parents, may benefit from an intensive
      family competence programme.

PMID- 16448483
TI  - Readjustment 5 months after a first-time myocardial infarction: reorienting the
      active self.
AB  - AIM: This paper reports on an interview study exploring the self-regulation
      process in women and men, 5 months after a first-time myocardial infarction.
      BACKGROUND: Somatic, psychological and social factors affect readjustment after a
      first-time myocardial infarction, and studies have demonstrated substantial rates
      of depression in patients after myocardial infarction Women report poorer mental
      health and physical condition than do men. Reconstruction of the self begins when
      disease poses novel problems and is more likely to occur in cases of long-lasting
      and disruptive illnesses. Experiencing myocardial infarction is likely to alter a
      person's mental representation of self. However, the self-regulation process
      following first-time myocardial infarction is not yet fully understood. METHOD:
      Twenty-one people (11 women, 10 men) were interviewed 5 months after first-time
      myocardial infarction. The grounded theory method provided the strategies for
      data collection and analysis. FINDINGS: Interviewees' definition of themselves as
      active was threatened by fatigue and other health problems that kept them from
      taking part in activities as they had done before the heart attack. Although
      reorienting the active self was central to the process of recovery from
      myocardial infarction, reorienting was restricted by illness perception and
      coping. CONCLUSION: Participants had not established a stable health condition 5
      months after first-time myocardial infarction. They mainly preferred to moderate
      rather than radically change their daily life activities. They needed more
      knowledge and support. Nurses can help with information and advice on managing
      daily life activities, including dialogue about lifestyle changes at this phase
      of readjustment.

PMID- 16448484
TI  - Nursing attitudes and beliefs in pain assessment and management.
AB  - AIMS: This paper reports a study to determine nurses' attitudes towards pain
      assessment tools and the relationship of these attitudes to education and
      experience. BACKGROUND: The issue of pain management is of interest to caregivers
      nationally and internationally. For example, in the United States of America, the
      National Health and Medical Research Council set guidelines to assist clinicians
      in pain management. Research on whether healthcare teams use pain assessment
      tools has yielded contradictory findings. METHODS: Using an open-ended
      questionnaire developed for this study, which was based on Fishbein and Ajzen
      expectancy-value model, a convenience sample of 52 nurses on an acute care unit
      were asked: (1) What do you believe about the assessment of pain? (2) What do you
      believe about the use of pain assessment tools? and (3) What do you believe about
      the use of pain assessment tools in improving the patient's outcome? The nurses
      then rated their attitudes about each belief and how each belief made them feel.
      The data were collected in 2003. Results. When Fishbein and Ajzen's formula for
      calculating attitude was used, attitude scores ranged from -6 to 28 with an
      overall mean score of +8.3. The amount of education and experience of each nurse
      and the attitude measure in regard to the use of pain assessment tools were
      compared. CONCLUSIONS: The Fishbein and Ajzen model provides a useful way to
      obtain information on the attitude of nurses towards the use of pain assessment
      instruments. To provide further information, this study with an open-ended
      instrument should be followed with a fixed-response survey with a larger sample
      size and in various settings.

PMID- 16448485
TI  - Communicative sensitivity in the bilingual healthcare setting: a qualitative
      study of language awareness.
AB  - AIM: This paper reports on the second phase of a national study in Wales. The
      research aimed to assess the level of Welsh language awareness amongst healthcare
      professionals across Wales, and to identify the factors that enhance language
      choice within service delivery. BACKGROUND: The literature suggests that language
      sensitive healthcare practice is central to ensuring high quality care. However,
      it is evident that language barriers continue to compromise the quality of care
      within nursing and other health services. One issue that has received little
      attention is the level of language awareness that healthcare professionals
      currently demonstrate. Furthermore the factors that influence language choice for
      bilingual/multilingual speakers are not well explored in the literature. METHODS:
      The study involved semi-structured interviews with a range of healthcare
      professionals in acute and community settings across Wales. Using a systematic
      sampling matrix, a purposeful sample of 83 professionals was selected to
      participate. Twenty-seven of the respondents were nurses, health visitors and
      midwives. The interviews focussed on the factors that facilitate or impede
      language sensitive healthcare practice. All interviews were audiotaped and, using
      a framework analysis approach, conceptual codes were developed and defined and
      categories and sub-categories were constructed to create thematic charts.
      FINDINGS: Three main themes were identified: care enhancement, which focussed on
      the process and outcome of offering language choice to bilingual patients;
      organizational issues, which reflected issues relating to the infrastructure of
      service provision; and training implications, which focused on Welsh language
      learning in health care. CONCLUSIONS: Complex dynamics of language use are in
      operation within bilingual healthcare settings and organizational as well as
      individual factors are important in facilitating appropriate language use. Many
      of the issues highlighted are not peculiar to the Welsh context, but apply to
      healthcare settings across the world, where other minority languages are in use.

PMID- 16448486
TI  - Lived experiences of family caregivers of mentally ill relatives.
AB  - AIM: The aim of this paper is to report a study conducted to explore the meanings
      of the lived experiences that Chinese family caregivers in Malaysia ascribed to
      the care they provided to relatives with severe and persistent mental illness.
      BACKGROUND: In the past, many researchers have used quantitative approaches to
      explore the experiences of family caregivers of relatives with severe and
      persistent mental illness. However, the results of these studies have been far
      from conclusive because of serious methodological flaws. In addition, a large
      majority of these studies were conducted in western cultures, and it has been
      difficult to transfer the results to family caregivers in oriental cultures.
      METHOD: The philosophy of Martin Heidegger underpinned the study. Qualitative
      data were collected mainly through in-depth interviews with 19 criterion-selected
      Chinese family caregivers of relatives with severe and persistent mental illness
      in 2002. FINDINGS: We present the emergent themes reflecting the meaning
      structures of managing, enduring, and surviving the day-to-day experiences of the
      Chinese family caregivers. The impact of the stigma of the relatives' mental
      illness on family caregivers and families is pervasive and strong. As a result,
      family caregivers tried to avoid talking about their relative's mental illness
      with extended family or friends in order to protect their families from 'losing
      face'. In addition, most family caregivers believed that adopting positive
      behaviours and attitudes helped them cope with caregiving. CONCLUSION: Mental
      health nurses need to help Chinese family caregivers to cope with the stresses
      and stigmas of their relatives' mental illnesses through psychosocial education
      or family intervention, and to provide them with culturally-congruent care. They
      should also educate the public about mental health and ill health through health
      promotion and education.

PMID- 16448487
TI  - Conflict within nursing work environments: concept analysis.
AB  - AIM: The aim of this paper is to examine the concept of conflict in nursing work
      environments using the evolutionary approach to concept analysis. BACKGROUND: In
      nursing work environments, conflict among nurses is becoming a significant issue
      resulting in job dissatisfaction, absenteeism, and turnover. Although discussed
      frequently in the nursing literature, nursing research has focused predominantly
      on conflict management without first understanding the elements, causes and
      effects of conflict. METHODS: A literature search was conducted using CINAHL,
      Proquest, PsychINFO, Social Sciences Index and MEDLINE databases and the keywords
      conflict and work environment. Articles over the last 25 years from each of these
      databases were examined to identify major themes, areas of agreement and
      disagreement across disciplines, changes in the concept over time, and emerging
      trends. FINDINGS: Conflict is a multidimensional construct with both detrimental
      and beneficial effects. Most definitions agree that conflict is a process
      involving two or more people, where a person perceives the opposition of the
      other. Antecedents stem from individual characteristics, interpersonal factors,
      and organizational factors. Individual effects, interpersonal relationships, and
      organizational effects are the main consequences of conflict. A theoretical model
      of the antecedents and consequences is presented, with implications for further
      development. CONCLUSIONS: A more thorough understanding of the sources and
      outcomes of conflict within nursing work environments would enable the prevention
      of conflict. If properly understood and managed, conflict can also lead to
      positive outcomes for nurses and healthcare organizations.

PMID- 16448488
TI  - Development of an evidence-based practice questionnaire for nurses.
AB  - AIM: The aim of this paper is to report the development and validation of a self
      report measure of knowledge, practice and attitudes towards evidence-based
      practice (EBP). BACKGROUND: Evidence-based practice has become increasingly
      important in health care since the mid-1990s as it provides a framework for
      clinical problem-solving. However, to date no means exist to quantify the extent
      to which barriers, such as lack of time in the working day, lack of appropriate
      skills and negative attitudes, may prevent greater uptake of EBP. METHODS:
      Questionnaire development was based on established psychometric methods.
      Principal component factor analysis was used to uncover the underlying dimensions
      of the scale. Internal consistency of the scale was assessed by Cronbach's alpha.
      Finally, construct validity was assessed via convergent and discriminant
      validity. RESULTS: The final questionnaire comprised three distinct scales (EBP,
      attitudes towards EBP and knowledge of EBP), which had robust validity and
      internal reliability. CONCLUSION: This tool can be used to measure the
      implementation of EBP.

PMID- 16448489
TI  - Understanding paradigms used for nursing research.
AB  - AIMS: The aims of this paper are to add clarity to the discussion about paradigms
      for nursing research and to consider integrative strategies for the development
      of nursing knowledge. BACKGROUND: Paradigms are sets of beliefs and practices,
      shared by communities of researchers, which regulate inquiry within disciplines.
      The various paradigms are characterized by ontological, epistemological and
      methodological differences in their approaches to conceptualizing and conducting
      research, and in their contribution towards disciplinary knowledge construction.
      Researchers may consider these differences so vast that one paradigm is
      incommensurable with another. Alternatively, researchers may ignore these
      differences and either unknowingly combine paradigms inappropriately or neglect
      to conduct needed research. To accomplish the task of developing nursing
      knowledge for use in practice, there is a need for a critical, integrated
      understanding of the paradigms used for nursing inquiry. METHODS: We describe the
      evolution and influence of positivist, postpositivist, interpretive and critical
      theory research paradigms. Using integrative review, we compare and contrast the
      paradigms in terms of their philosophical underpinnings and scientific
      contribution. FINDINGS: A pragmatic approach to theory development through
      synthesis of cumulative knowledge relevant to nursing practice is suggested. This
      requires that inquiry start with assessment of existing knowledge from disparate
      studies to identify key substantive content and gaps. Knowledge development in
      under-researched areas could be accomplished through integrative strategies that
      preserve theoretical integrity and strengthen research approaches associated with
      various philosophical perspectives. These strategies may include parallel studies
      within the same substantive domain using different paradigms; theoretical
      triangulation to combine findings from paradigmatically diverse studies;
      integrative reviews; and mixed method studies. CONCLUSION: Nurse scholars are
      urged to consider the benefits and limitations of inquiry within each paradigm,
      and the theoretical needs of the discipline.

PMID- 16448490
TI  - Evaluation of a cultural competence educational programme.
AB  - AIM: This paper reports a study, which evaluated the effectiveness of a cultural
      competence educational programme to increase Public Health Nurses' cultural
      knowledge. BACKGROUND: Cultural competence has great significance for practising
      nurses and has become a priority and commitment of the Nursing profession. Public
      Health Nurses interact regularly with clients from a variety of culturally
      diverse backgrounds. Thus, there is a need for an integrated programme with
      theoretical and experiential knowledge related to cultural competence for PHNs to
      enhance their knowledge and skills to better meet the needs of the population.
      DESIGN: This study used a combination of quantitative and qualitative methods for
      data collection. A one-group Repeated Measures design was used to evaluate the
      effectiveness of the educational programme. METHOD: The sample consisted of 76
      Public Health Nurses who attended a cultural competence educational programme,
      which was offered over five consecutive weeks, of 2 hours duration and reinforced
      by a booster session at 1 month postimplementation of the programme. Cultural
      knowledge was measured on the Cultural Knowledge Scale, which was a valid,
      reliable, 25-item Likert scale. Data were collected at four points in time and
      were analysed with repeated measures analysis of variance. Qualitative data were
      content analysed. RESULTS: Findings revealed that the intervention was effective
      [Wilks' Lambda was F(3,69) = 142.02, P < 0.01] in increasing the nurses' cultural
      knowledge. Qualitative results complemented the quantitative findings.
      Participants reported that the programme was effective in increasing their
      cultural knowledge. CONCLUSION: Although Public Health Nurses, who attended the
      educational programme increased their cultural knowledge, these findings are not
      generalizable to nurses working in other settings. However, the programme has
      clinical utility and could be adapted and given to nurses in other settings.

PMID- 16448491
TI  - Communication skills and cultural awareness courses for healthcare professionals
      who care for patients with sickle cell disease.
AB  - AIMS: This paper reports a project evaluating the efficacy and impact of a pilot
      communication skills and cultural awareness course for healthcare professionals
      who care for patients with sickle cell disease. BACKGROUND: Poor communication
      between patients with sickle cell disease and healthcare professionals causes
      suspicion and mistrust. Many patients feel that they are negatively labelled by
      the healthcare system and are sceptical of opening themselves to an unsympathetic
      system. They may therefore appear hostile and aggressive when interacting with
      healthcare professionals, which in turn leads to distortions and
      misunderstandings between both groups. The use of good communication skills by
      healthcare professionals is therefore vital for good healthcare practice.
      METHODS: Forty-seven healthcare professionals took part in a series of three
      pilot courses each lasting 3 days. Healthcare professionals were taught a
      repertoire of communication skills and cultural awareness strategies to use in
      challenging situations that arise in their care of sickle cell patients. Expert
      facilitators used a variety of teaching techniques, such as professionally-made
      videos, role-play, and group exercises. Participants' confidence in dealing with
      challenging situations was assessed at baseline, immediately after the
      intervention, and at 3- and 6-month postintervention. FINDINGS: A repeated
      measures anova revealed a statistically significant increase in confidence from
      pre- to postcourse scores. Confidence scores further increased from immediately
      postcourse and 3 months postcourse follow-up. These were then maintained at 6
      months postcourse. CONCLUSION: The overall findings of this local study
      demonstrated that this type of communication skills and cultural awareness
      training had a positive and enduring impact on professionals' perceived ability
      and confidence in communicating with patients with sickle cell disease.
      Participants attributed this to the learner-centred approach of the course that
      provided them with the opportunity to transfer and apply the taught skills in
      their daily practice. This type of training might be helpful in reducing mistrust
      and increasing empathetic responses in healthcare professional.

PMID- 16448494
TI  - Type II secretion: from structure to function.
AB  - Gram-negative bacteria use the type II secretion system to transport a large
      number of secreted proteins from the periplasmic space into the extracellular
      environment. Many of the secreted proteins are major virulence factors in plants
      and animals. The components of the type II secretion system are located in both
      the inner and outer membranes where they assemble into a multi-protein, cell
      envelope spanning, complex. This review discusses recent progress, particularly
      newly published structures obtained by X-ray crystallography and electron
      microscopy that have increased our understanding of how the type II secretion
      apparatus functions and the role that individual proteins play in this complex
      system.

PMID- 16448495
TI  - A comparison of enteropathogenic and enterohaemorrhagic Escherichia coli
      pathogenesis.
AB  - This review covers enteropathogenic Escherichia coli (EPEC) and
      enterohaemorrhagic E. coli (EHEC) infections, focusing on differences in their
      virulence factors and regulation. While Shiga-toxin expression from integrated
      bacteriophages sets EHEC apart from EPEC, EHEC infections often originate from
      asymptomatic carriage in ruminants whereas human EPEC are considered to be overt
      pathogens and more host-restricted. In part, these differences reflect variation
      in adhesin repertoire, type III-secreted effectors and the way in which these
      factors are regulated.

PMID- 16448496
TI  - Biodegradation of ochratoxin A by Aspergillus section Nigri species isolated from
      French grapes: a potential means of ochratoxin A decontamination in grape juices
      and musts.
AB  - Ochratoxin A (OTA) is a very dangerous mycotoxin, the presence of which is often
      reported in different foods, as well as in beverages such as grapes, grape juices
      and wines. Detoxifying these products is therefore of prime importance in
      protecting consumer health, and biological approaches have been the most
      promising methods. In this report, 40 isolates representing the black apergilli
      species Aspergillus carbonarius, A. niger aggregate and A. japonicus, isolated on
      French grapes, were assessed for OTA degradation capacities in CZAPEK yeast
      extract broth (CYB) and in a synthetic grape juice medium (SGM) contaminated with
      OTA at 2 mg L(-1) (5 microM). It was clearly observed that in both media these
      fungi had the ability to degrade OTA to OTalpha (ochratoxinalpha). However, there
      were differences between the media used and species tested during OTA
      degradation. In SGM and CYB, 77% and 45% of the isolates, respectively were able
      to degrade more than 80% of the OTA. Despite a better growth on SGM, specific OTA
      degradation was higher on CYB for most of the isolates. Kinetic studies carried
      out on SGM with three black Aspergillus isolates all showed different OTA
      degradation rates. After 9 days of incubation, OTalpha had decreased, whereas an
      unknown compound appeared. A. niger could be the first interesting species for
      OTA detoxification processes, followed by A. japonicus.

PMID- 16448498
TI  - Carotenoids present in halotolerant Bacillus spore formers.
AB  - Six isolates of pigmented spore-forming bacteria were recovered from human faeces
      from subjects in Vietnam. 16S rRNA analysis demonstrated close association with
      known pigmented Bacillus species. All isolates were able to tolerate growth on 8%
      NaCl and were resistant to arsenate, characteristics that make them most related
      to Bacillus indicus. Two visible pigments were apparent, a yellow pigment found
      in vegetative cells and an orange pigment found only in spores. We used high
      performance liquid chromatography to characterize and quantify these pigments and
      found them to be carotenoids. The biosynthetic pathway that generates them
      branches with one that could lead to the spore-associated orange pigmentation.
      Although these bacteria were found in faeces, the seafood-rich diet of Vietnam
      and the recovery of other pigmented Bacillus species from seafood and marine
      environments makes it highly probable that the true origin of these bacteria is
      from ingested seafood.

PMID- 16448497
TI  - Pythium sterilum sp. nov. isolated from Poland, Spain and France: its morphology
      and molecular phylogenetic position.
AB  - In a survey of Phytophthora species associated with forest decline in Spain,
      Poland and France, we found three Pythium isolates, which have been characterized
      with internal transcribed spacer rRNA gene sequences and with classical
      morphological descriptors for Pythium spp. These isolates showed unique internal
      transcribed spacer sequences, different enough from those of any described
      species to justify new species status. These three distinct isolates failed to
      produce any sex organs with an entirely asexual reproduction and were found to
      represent a new species for which the name Pythium sterilum is proposed. This
      paper describes and illustrates the morphology of P. sterilum and presents its
      taxonomic position and relationships with other, related Pythium species
      belonging to clade K.

PMID- 16448499
TI  - Diversity of soluble methane monooxygenase-containing methanotrophs isolated from
      polluted environments.
AB  - Methanotrophs were enriched and isolated from polluted environments in Canada and
      Germany. Enrichments in low copper media were designed to specifically encourage
      growth of soluble methane monooxygenase (sMMO) containing organisms. The 10
      isolates were characterized physiologically and genetically with one type I and
      nine type II methanotrophs being identified. Three key genes: 16S rRNA; pmoA and
      mmoX, encoding for the particulate and soluble methane monooxygenases
      respectively, were cloned from the isolates and sequenced. Phylogenetic analysis
      of these sequences identified strains, which were closely related to
      Methylococcus capsulatus, Methylocystis sp., Methylosinus sporium and
      Methylosinus trichosporium. Diversity of sMMO-containing methanotrophs detected
      in this and previous studies was rather narrow, both genetically and
      physiologically, suggesting possible constraints on genetic diversity of sMMO due
      to essential conservation of enzyme function.

PMID- 16448500
TI  - The discriminatory power of MALDI-TOF mass spectrometry to differentiate between
      isogenic teicoplanin-susceptible and teicoplanin-resistant strains of methicillin
      resistant Staphylococcus aureus.
AB  - To explore the discriminatory power of matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS) for detecting subtle
      differences in isogenic isolates, we tested isogenic strains of Staphylococcus
      aureus differing in their expression of resistance to methicillin or teicoplanin.
      More important changes in MALDI-TOF MS spectra were found with strains differing
      in methicillin than in teicoplanin resistance. In comparison, very minor or no
      changes were recorded in pulsed-field gel electrophoresis profiles or
      peptidoglycan muropeptide digest patterns of these strains, respectively. MALDI
      TOF MS might be useful to detect subtle strain-specific differences in ionizable
      components released from bacterial surfaces and not from their peptidoglycan
      network.

PMID- 16448501
TI  - Osmotic stress responses of Streptococcus mutans UA159.
AB  - The hyperosmotic stress response of Streptococcus mutans was investigated. Real
      time reverse transcriptase-PCR and slot-blot analysis revealed that opuAA, opcA,
      Smu.2115, sodA and nox were induced after exposure to 0.4 M NaCl. Our data
      suggest that there is a cross-talk between osmotic and oxidative stress responses
      in S. mutans. Inactivation of Smu.2115, encoding a putative oxidoreductase,
      resulted in an acid-resistant and hydrogen peroxide-sensitive phenotype.

PMID- 16448502
TI  - mvaT mutation modifies the expression of the Pseudomonas aeruginosa multidrug
      efflux operon mexEF-oprN.
AB  - Pseudomonas aeruginosa carries several multidrug efflux operons, including mexEF
      oprN, that contribute to its resistance to multiple antibiotics. mvaT affects the
      expression of several P. aeruginosa genes. In this study, we show that the mvaT
      mutant PAODeltamvaT is more resistant than its parent PAO1 strain to
      chloramphenicol and norfloxacin but more sensitive to imipenem; yet both were
      less resistant to chloramphenicol, norfloxacin, and imipenem than 'typical'nfxC
      type mutants. Neither strain carries the deletion described for nfxC-type mutants
      in mexT, the mexEF-oprN regulatory gene. Expression of mexEF-oprN is increased by
      five- to sixfold in PAODeltamvaT, while the expression of oprD is reduced by
      approximately twofold. mvaT mutation had no effect on the expression of other
      multidrug resistance operons, although it increased the expression of several ATP
      binding cassette transporter genes. We show that mvaT mutation does not affect
      mexEF-oprN expression through mexT or mexS. We also explored several other
      potential mechanisms.

PMID- 16448503
TI  - Reduction in solanapyrone phytotoxin production by Ascochyta rabiei transformed
      with Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens was used to transform Ascochyta rabiei, the causal
      agent of chickpea blight. Employing a T-DNA containing a hygromycin resistance
      gene (hph), 908 transformants were obtained from germinated pycnidiospores on a
      selective medium containing hygromycin. Transformants were confirmed using PCR
      and Southern analyses and of four of these that were tested, two had integrated
      multicopies of the hph gene, one had two copies and one had a single insertion.
      Transformants were tested for the production of solanapyrone A toxin using a
      microtitre plate assay. Loss of toxin production by transformants was confirmed
      by reversed phase high-performance liquid chromatography. Sixteen transformants
      out of 668 tested produced significantly less solanapyrone A than the wild-type
      strain.

PMID- 16448504
TI  - Aerobic activation of transcription of the anaerobically inducible Escherichia
      coli focA-pfl operon by fumarate nitrate regulator.
AB  - Expression of the anaerobically inducible focA-pfl operon in Escherichia coli was
      activated nearly sevenfold relative to wild-type under aerobic growth conditions
      by increasing the dosage of the fnr gene on a pBR322-based plasmid (pCH21). No
      effect on anaerobic expression levels was observed, suggesting that operon
      expression under these conditions is maximal. Examination of the complex
      transcript pattern of the focA-pfl operon confirmed that in strains bearing pCH21
      all transcripts, with the exception of the promoter 7 transcript, were up
      regulated aerobically. Western analysis of strains bearing pCH21 revealed that
      the fumarate nitrate regulator (FNR) level was increased approximately ninefold
      relative to the level in strains bearing a single copy of the fnr gene
      aerobically, but was only overproduced threefold anaerobically. Analysis of an
      fnr-lacZ fusion indicated that fnr expression was more strongly negatively
      autoregulated in anaerobic cells compared with aerobic cells when pCH21 was
      present. Taken together, these findings suggest that high-level overproduction of
      FNR is prevented anaerobically by active FNR repressing expression of the fnr
      gene. Furthermore, transcription from promoter 7 of the focA-pfl operon, which
      depends on both ArcA-P and FNR, cannot be activated aerobically by overproduction
      of FNR alone, while promoter 6, which is less dependent on ArcA-P, can be
      activated under these conditions.

PMID- 16448505
TI  - Impact of amino acid changes in the signal peptide on the secretion of the Tat
      dependent xylanase C from Streptomyces lividans.
AB  - Xylanase C (XlnC) is a cofactorless protein secreted through the twin arginine
      translocation (Tat)-dependent secretion pathway by Streptomyces lividans. Its
      signal peptide contains the SRRGFLG sequence, which is similar to the twin
      arginine consensus motif. The 49 amino acid-long signal peptide was analyzed by
      random, site-directed and site-saturation mutagenesis and the effect of these
      mutations on XlnC secretion determined. None of the mutations abolished XlnC
      production and the decreased yields were attributed to the low processing rate of
      precursors ranging from 2 to 5 h instead of 11 min for the wild-type precursor.
      Replacement of phenylalanine in the consensus motif by other amino acid residues
      decreased XlnC secretion by 75%, except for a tryptophan substitution which
      demonstrated a 50% decrease. Charge distribution in the n-domain of the signal
      peptide was more important than the net charge. Replacement of the signal
      peptidase recognition site A-H-A by either A-H-E, V-D-S or R-L-E did not affect
      precursor processing, indicating that the presence of the conserved residues
      found in the signal peptidase recognition site is not a prerequisite for the
      processing of Tat-substrates as it is for the processing of Sec-substrates in S.
      lividans.

PMID- 16448506
TI  - The aflatoxin pathway regulator AflR induces gene transcription inside and
      outside of the aflatoxin biosynthetic cluster.
AB  - Aflatoxin contamination of food and feed is a major concern due to the
      carcinogenic properties of this mycotoxin. Previous studies using classical
      approaches have identified a cluster of genes responsible for aflatoxin
      production under the control of the pathway-specific transcriptional regulator
      aflR, but it is unknown whether aflR controls expression of other genes within
      the genome. Transcription profiling comparing wild type and DeltaaflR strains of
      Aspergillus parasiticus grown under conditions conducive for aflatoxin production
      identified only 23 upregulated genes in the wild type. These included 20 genes in
      the aflatoxin biosynthetic cluster, and three additional genes outside the
      aflatoxin biosynthetic cluster (nadA, hlyC, and niiA), all with AflR binding
      sites. This report is the first to demonstrate genes outside the biosynthetic
      cluster as being associated with aflR expression.

PMID- 16448507
TI  - A putative proteinase gene is involved in regulation of landomycin E biosynthesis
      in Streptomyces globisporus 1912.
AB  - The prx gene, which is highly homologous to putative proteinases, has been
      identified by sequencing in the vicinity of the biosynthetic gene cluster for
      landomycin E (LaE) biosynthesis (lnd) in Streptomyces globisporus 1912. The S.
      globisporus Pro6 gene, deficient in prx, produced fivefold less LaE than the
      parental strain. The expression of prx in S. globisporus Pro6 restored LaE
      production to wild-type levels, whereas expression of the pathway-specific
      regulatory gene lndI did not. The introduction of additional copies of prx into
      the wild-type strain using a pSG5-based plasmid, pKC1139, led to a 2.7-fold
      increase in LaE production. These results indicate that prx is a novel regulatory
      gene for LaE biosynthesis.

PMID- 16448508
TI  - A broadly applicable method for extraction and characterization of mycosporines
      and mycosporine-like amino acids of terrestrial, marine and freshwater origin.
AB  - A universal method allowing simultaneous extraction and analysis of diverse
      ultraviolet-B-absorbing compounds belonging to mycosporines and mycosporine-like
      amino acids (MAAs) is presented. Mycosporines and MAAs are found both in
      prokaryotes and eukaryotes and possess photoprotective properties. Our method was
      successfully tested by screening 31 cyanobacterial, 11 actinomycete and 45 fungal
      strains for their mycosporine and MAA content. The majority of the isolates
      tested originated from subaerial rock surfaces and were inherently protected from
      excessive sun irradiation. The new method includes a solid-liquid extraction
      procedure, followed by a reversed phase liquid chromatography/mass spectrometry.
      Eight different mycosporines and five MAAs were efficiently separated and
      identified by their retention times, absorption maxima and fragmentation
      patterns. Mycosporines were found both in rock-inhabiting fungi and cyanobacteria
      and consequently may render an ecological marker of these peculiar terrestrial
      environments.

PMID- 16448509
TI  - Munumbicins E-4 and E-5: novel broad-spectrum antibiotics from Streptomyces NRRL
      3052.
AB  - Streptomyces NRRL 30562 was originally isolated as an endophyte from Kennedia
      nigriscans, snakevine, in the Northern Territory of Australia. This plant has
      been used for centuries by Aboriginal peoples to treat open bleeding wounds to
      prevent sepsis. A solvent extract of the crude fluid from cultures of this
      endophyte possesses wide-spectrum antibiotic activity. Some of the bioactivity is
      associated with the appearance of actinomycins X2, D, and Xobeta, the first two
      of which had been previously designated munumbicins A and B, respectively. Other
      novel compounds bearing wide-spectrum antibiotic activity are also produced by
      Streptomyces NRRL 30562, and these are designated munumbicins E-4 and E-5. Mass
      spectrometric analyses of these peptide antibiotics show that they have identical
      masses (1445.00) but different retention times on HPLC. Both compounds showed
      activity against gram-positive and gram-negative bacteria. The plant pathogenic
      fungus, Pythium ultimum is sensitive to both munumbicins at 5.0 microg mL(-1) The
      malarial parasite, Plasmodium falciparum has IC50 values of 0.50+/-0.08 and
      0.87+/-0.0.26 microg mL(-1) for E-4 and E-5, respectively. It appears that other
      bioactive compounds, related to E-4 and E-5, are also produced making it the most
      biologically active endophytic Streptomyces spp. on record.

PMID- 16448510
TI  - Differential green fluorescent protein expression from mycobacterial promoter
      constructs in Escherichia coli and Mycobacterium marinum.
AB  - The Mycobacterium marinum G13 promoter is a sigma 70-like promoter that is more
      active by green fluorescent protein (gfp) differential fluorescence induction
      (DFI) assays when M. marium resides in an intracellular compartment as compared
      with growth in media. In assays using DFI, we found that the mycobacterial G13
      promoter was also more active in a background of lower nutrient availability
      during logarithmic growth. This promoter, contained in an insert cloned upstream
      of a gfp reporter gene, is also active in Escherichia coli. When gfp expression
      assays of different plasmid constructs were performed in parallel with E. coli
      and M. marinum, expression in E. coli was maintained after deletion of both
      upstream and/or downstream regions proximal to the core promoter sequence. In M.
      marinum, however, although upstream deletions had no appreciable effect on gfp
      expression, promoter constructs with deleted downstream regions expressed 20- to
      40-fold less gfp over all growth phases. The high-level expression of gfp was
      restored, however, in a clone containing approximately 100 bp downstream of the
      transcriptional start point. We have therefore utilized this gfp reporter assay
      of promoter activity to distinguish possible differences in requirements for gfp
      expression between different genera that utilize sigma 70-like promoter elements.
      We found that high levels of expression of gfp from the G13 promoter in M.
      marinum require downstream regions not necessary for gfp expression in E. coli.

PMID- 16448511
TI  - Atomic force microscopic study of the effects of ethanol on yeast cell surface
      morphology.
AB  - The detrimental effects of ethanol toxicity on the cell surface morphology of
      Saccharomyces cerevisiae (strain NCYC 1681) and Schizosaccharomyces pombe (strain
      DVPB 1354) were investigated using an atomic force microscope (AFM). In
      combination with culture viability and mean cell volume measurements AFM studies
      allowed us to relate the cell surface morphological changes, observed on
      nanometer lateral resolution, with the cellular stress physiology. Exposing
      yeasts to increasing stressful concentrations of ethanol led to decreased cell
      viabilities and mean cell volumes. Together with the roughness and bearing volume
      analyses of the AFM images, the results provided novel insight into the relative
      ethanol tolerance of S. cerevisiae and Sc. pombe.

PMID- 16448512
TI  - p-hydroxylation reactions catalyzed by naphthalene dioxygenase.
AB  - In this study, naphthalene dioxygenase is shown to catalyze the oxidation of
      methylphenols and chlorophenols by p- and/or o-hydroxylation reactions. For
      instance, m-cresol was oxidized to methylhydroquinone with formation of 3- and 4
      methylcatechol as minor products. 2-Chlorophenol was exclusively oxidized to
      chlorohydroquinone, which is an important building block for pharmaceutical
      products and other organic compounds. The oxygen incorporated in the p
      hydroxylation reaction from m-cresol is derived from water with consumption of
      O2.

PMID- 16448515
TI  - Opportunities for gene therapy in preventing vein graft failure after coronary
      artery bypass surgery.
AB  - The poor patency rates for coronary artery bypass grafting (CABG) using
      autologous saphenous vein necessitate the need for continued research into the
      potential clinical utility of gene therapy. Bypass grafting is ideally suited for
      gene therapy, as graft can be genetically modified ex vivo prior to grafting in
      the coronary vasculature. Research to date has demonstrated effective blockade of
      late vein graft failure through overexpression of a variety of transgenes that
      modulate the proliferative, migratory and/or apoptotic indexes of cells in the
      graft wall. This has resulted in a substantial wealth of preclinical data that
      support advancement to clinical trials. Future translation into clinical trials
      will ensure that this exciting and highly relevant area of gene therapy is fully
      evaluated for potential routine clinical practice to improve patency rates of
      bypass graft procedures involving saphenous vein.

PMID- 16448513
TI  - Yeast autonomous linear plasmid pGKL2: ORF9 is an actively transcribed essential
      gene with multiple transcription start points.
AB  - A pair of linear plasmids, pGKL1 (8.9 kb) and pGKL2 (13.4 kb), resides in the
      cytoplasm of Kluyveromyces lactis killer strains. The smaller element, actually
      conferring the killer phenotype, strictly depends on the larger autonomous pGKL2.
      Here, we have examined the previously uncharacterized pGKL2 open reading frame
      (ORF)9 (1.34 kb). Northern analysis of a killer plasmid carrying Saccharomyces
      cerevisiae strain applying an ORF9-specific probe revealed a single transcript
      closely matching the size of the ORF9 coding region. Multiple transcriptional
      start points, determined by primer extension analysis, are located 16 nt
      downstream of a conserved sequence element regarded as the cytoplasmic promoter.
      In vivo disruption of pGKL2/ORF9 using the cytoplasmically expressible marker
      gene LEU2* resulted in the establishment of a three-plasmid system composed of
      the native cytoplasmic elements pGKL1/2 and a hybrid of the latter, which only
      remained stable under selective conditions. The native pGKL2, however, did not
      segregate during prolonged subcultivations, proving an essential function of ORF9
      for plasmid maintenance.

PMID- 16448516
TI  - Association between antipsychotic drugs and diabetes.
AB  - The link between atypical antipsychotic drugs and the development of diabetes has
      been hotly debated in the literature. In this review, we attempt to classify the
      various types of data published and presented in a hierarchical basis. Case
      reports and retrospective pharmacoepidemiological studies suggest that both
      conventional and atypical antipsychotic medications are associated with an
      increased risk of glucose abnormalities or diabetes. Prospective data examining
      the relationship between atypical antipsychotic drugs and diabetes began to
      emerge in 2003 and are much less conclusive. Estimates of the attributable risk
      associated with atypical antipsychotic drugs are low. The few studies that have
      included a placebo group suggest that we cannot necessarily blame antipsychotic
      medication when diabetes develops in an individual with schizophrenia.

PMID- 16448517
TI  - Reactive species and early manifestation of insulin resistance in type 2
      diabetes.
AB  - The early stages of type 2 diabetes mellitus are characterized by the development
      of insulin resistance (IRe) in muscle cells and adipocytes with the concomitant
      loss of beta-cell compensation. We have extensively reviewed the literature
      related to metabolic and signalling pathways of reactive oxygen species (ROS) in
      regard to the coordinated development of oxidative stress and IRe. We considered
      the hypothesis that oxidative stress leads to IRe in muscle cells and adipocytes,
      but found that the data are more consistent with the hypothesis that the cellular
      mechanisms that protect against oxidative stress per se are capable of creating
      an ROS-dependent insulin-resistant state. Furthermore, ROS-induced mitochondrial
      dysfunction can lead to disruptions of lipid metabolism, increasing the
      intracellular lipid content, and, in addition, contribute to lipid-dependent IRe
      in myocytes. Together, these two ROS-activated pathways to IRe can contribute to
      a global state of profound resistance to insulin action. Therapeutic strategies
      should, therefore, be directed towards reducing insulin resistance without an
      increase in ROS production or concentration. Pharmacological or other approaches
      to IRe that result in the activation of mitochondrial biogenesis in particular
      could be highly beneficial in the prevention or treatment of both insulin
      resistance and type 2 diabetes.

PMID- 16448518
TI  - Use of packaged entrees as part of a weight-loss diet in overweight men: an 8
      week randomized clinical trial.
AB  - AIM: This study assessed the efficacy of a weight-loss diet by using packaged
      portion-controlled entrees vs. a self-selected diet based on the United States
      Department of Agriculture Food Guide Pyramid (FGP). METHODS: Sixty healthy
      overweight men (body mass index (BMI) 26-42 kg/m2; aged 24-60 years) were
      randomized into two groups for an 8-week intervention. Group E consumed two
      portion-controlled entrees daily, plus recommended servings from the FGP. Group P
      consumed a self-selected diet consisting of a recommended number of servings from
      the FGP. Diets were designed to be isocaloric (1700 kcal) and identical in
      macronutrient composition (55% carbohydrate, 25% protein and 20% fat).
      Participants were instructed to make no changes in physical activity levels. Each
      group was blinded to the protocol of the other group, and received separate diet
      instructions, but no behavioural or diet counselling. Outcomes included weight,
      BMI, body composition by dual energy X-ray absorptiometry, waist and hip
      circumference, blood pressure (BP), fasting blood lipids, glucose, insulin and C
      reactive protein. RESULTS: Fifty-one men completed the study. The portion-control
      group E (n = 25) experienced greater decreases in weight (-7.4 +/- 3.1 vs. -5.1
      +/- 4.0 kg), BMI (-2.4 +/- 1.0 vs. -1.6 +/- 1.3 kg/m2), fat mass (-3.6 +/- 1.8
      vs. -2.5 +/- 1.8 kg), waist circumference (-6.6 +/- 3.3 vs. -4.3 +/- 2.9 cm) and
      diastolic BP (-6.0 +/- 7.2 vs. + 0.2 +/- 10.1 mmHg) than group P (n = 26) (p <
      0.05). Consumption of a packaged entree diet resulted in greater losses of weight
      and fat mass, and reduced BP. CONCLUSIONS: Use of packaged entrees as part of a
      weight-loss diet is an effective means of achieving portion control and enhancing
      losses of weight and fat mass in overweight men.

PMID- 16448519
TI  - Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type
      2 diabetes inadequately controlled on metformin monotherapy.
AB  - AIM: This double-blind study evaluated the efficacy and safety of metformin
      glibenclamide tablets vs. metformin plus rosiglitazone therapy in patients with
      type 2 diabetes inadequately controlled on metformin monotherapy. SUBJECTS AND
      METHODS: After an open-label, metformin lead-in phase, 318 patients were randomly
      assigned to treatment based on metformin-glibenclamide 500/2.5 mg tablets
      (initial daily dose 1000/5 mg) or metformin 500 mg plus rosiglitazone 4 mg
      (initial daily dose 1000-2000 mg + 4 mg, depending on previous treatment) for 24
      weeks. Doses were titrated to achieve the therapeutic glycaemic target. The
      primary efficacy variable was the change in HbA1C. RESULTS: At week 24, metformin
      glibenclamide tablets resulted in significantly greater reductions in HbA1C (
      1.5%) and fasting plasma glucose [-2.6 mmol/l (-46 mg/dl)] than metformin plus
      rosiglitazone [-1.1%, p < 0.001; -2 mmol/l (-36 mg/dl), p = 0.03]. More patients
      receiving metformin-glibenclamide attained HbA1C <7.0% than did those in the
      metformin plus rosiglitazone group (60 vs. 47%) and had fasting plasma glucose
      levels <7 mmol/l (<126 mg/dl) by week 24 (34 vs. 25%). Both treatments were well
      tolerated. Frequency of adverse gastrointestinal events was comparable between
      groups. Four per cent of patients receiving metformin-glibenclamide withdrew
      because of symptomatic hypoglycaemia contrasted with 3% of patients receiving
      metformin plus rosiglitazone who withdrew because of persistent hyperglycaemia.
      Hypoglycaemic events were mild or moderate in intensity and were easily self
      managed. CONCLUSIONS: Metformin-glibenclamide tablets resulted in significantly
      greater reductions in HbA1C and fasting plasma glucose compared with metformin
      plus rosiglitazone in patients with type 2 diabetes inadequately controlled on
      metformin monotherapy.

PMID- 16448520
TI  - Addition of pioglitazone to stable insulin therapy in patients with poorly
      controlled type 2 diabetes: results of a double-blind, multicentre, randomized
      study.
AB  - AIM: To determine the effects of pioglitazone treatment combined with insulin on
      glucose and lipid metabolism in patients with type 2 diabetes. METHODS: In a
      multicentre, double-blind study, 690 patients [body mass index, 33.19 kg/m2 +/-
      5.47; haemoglobin A1c (A1C), 9.78 +/- 1.51; mean duration, 12.9 years] with
      diabetes poorly controlled with a stable insulin dose (> 30 U/day for > or =30
      days) were randomly allocated to pioglitazone 30 or 45 mg once daily for 24
      weeks. RESULTS: In the pioglitazone 30- and 45-mg groups, respectively, 71 and
      70% of patients completed the study. At 24 weeks, statistically significant, dose
      dependent mean decreases from baseline were seen in the pioglitazone 30- and 45
      mg groups for A1C (-1.17 and -1.46%, respectively) and fasting plasma glucose (
      31.9 and -45.8 mg/dl, respectively). Insulin dosage also decreased significantly
      (-4.5 and -7.3 U, respectively; p < or = 0.05) from baseline. Decreases in
      triglycerides [pioglitazone 45 mg: -5.9% (p < or = 0.05)], very low-density
      lipoprotein cholesterol [pioglitazone 45 mg: -6.2% (p < or = 0.05)] and free
      fatty acids [-0.94 (p < or = 0.05) and -2.13 (p < 0.0001) mg/dl, respectively]
      and increases in high-density lipoprotein cholesterol (9.7 and 13.0%,
      respectively; p < 0.0001) also were observed from baseline. Small but significant
      increases in total and low-density lipoprotein cholesterol (p < 0.01) from
      baseline were observed. Mean weight gain was 2.9 and 3.4 kg in the respective
      groups; lower limb oedema was reported in 13 and 12% of patients, respectively.
      The incidences of oedema, weight gain and heart failure were not higher than
      anticipated in this population. No evidence of hepatotoxicity or clinically
      significant elevations in liver function test parameters was seen. CONCLUSIONS:
      In patients with poorly controlled type 2 diabetes, addition of pioglitazone to
      insulin significantly improved glycaemic control, had a positive effect on
      important components of the lipid profile in a dose-dependent manner and was
      generally well tolerated.

PMID- 16448521
TI  - Tissue-specific regulation of malonyl-CoA decarboxylase activity in OLETF rats.
AB  - AIM: The intracellular concentration of malonyl-CoA, a key regulator of fatty
      acid oxidation, is determined both from its synthesis by acetyl-CoA carboxylase
      and from its degradation by malonyl-CoA decarboxylase (MCD). The aim of our study
      was to investigate the activity and mRNA expression of MCD under insulin
      resistance and after treatment with insulin sensitizers in different tissues.
      METHODS: We treated 18-week Otusuka Long-Evans Tokushima Fatty (OLETF) rats with
      pioglitazone (10 mg/kg/day) or metformin (300 mg/kg/day) for 8 weeks and
      determined the activity and mRNA expression of MCD in diabetic OLETF and non
      diabetic Long-Evans Tokushima Otsuka (LETO) rats in myocardial and skeletal
      muscles, and in liver. RESULTS: The MCD activities of myocardial and skeletal
      muscles were remarkably reduced in OLETF rats compared with LETO rats (995 +/-
      114 vs. 2012 +/- 359, 58 +/- 11 vs. 167 +/- 40 pmol/min/mg protein; p = 0.005 and
      p = 0.010). Surprisingly, after pioglitazone treatment, not after metformin, the
      MCD activities of myocardial and skeletal muscles (1906 +/- 320 and 259 +/- 44
      pmol/min/mg protein) increased up to the levels in LETO rats. MCD mRNA expression
      in OLETF rats was also reduced in myocardial and skeletal muscles vs. LETO rats
      (p = 0.049 and p = 0.008) and was unchanged by pioglitazone or metformin
      treatment. In the liver, MCD activity and mRNA expression were similar in OLETF
      and LETO rats. CONCLUSION: Pioglitazone treatment restored MCD activity to non
      diabetic level and improved the restrained fatty acid metabolism in myocardial
      and skeletal muscles caused by insulin-resistant diabetic status.

PMID- 16448522
TI  - Double-blind, randomized, multicentre study of the efficacy and safety of
      gliclazide-modified release in the treatment of Chinese type 2 diabetic patients.
AB  - BACKGROUND AND AIM: Gliclazide-modified release (gliclazide MR) is a new
      formulation of the sulfonylurea gliclazide designed for once-daily
      administration. The hydrophilic matrix of hypromellose-based polymer in the new
      formulation induces a progressive drug release, which parallels the 24-h
      glycaemic profile in type 2 diabetic patients. The aim of this study was to
      compare the efficacy and safety of gliclazide MR (once-daily administration)
      versus gliclazide (twice-daily administration) in Chinese type 2 diabetic
      patients. MATERIALS AND METHODS: Sixty-three type 2 diabetic Chinese patients who
      had been on diet control alone or on treatment with metformin or on low dose of
      sulfonylurea were randomized to either gliclazide MR taken once daily or
      gliclazide taken twice daily. Dosage of metformin was maintained throughout the
      study, and the sulfonylurea was stopped. The dose of gliclazide MR was increased
      at 1-month intervals from 30 mg to 120 mg, while that of gliclazide from 80 mg to
      320 mg until metabolic control was achieved [fasting plasma glucose (FPG) < or =
      7.7 mmol/l] or the maximum dose reached. Efficacy was mainly evaluated by levels
      of haemoglobin A1c (HbA1c) and FPG. RESULTS: The mean baseline characteristics of
      the full analysis set 1 (FAS1) (HbA1c, n = 58) and the FAS2 (FPG, n = 61) were
      comparable in both groups. The levels of HbA1c decreased similarly in both groups
      over the treatment period: -1.6 +/- 1.6% (p < 0.001) on gliclazide MR (n = 31)
      and -1.6 +/- 1.4% (p < 0.001) on gliclazide (n = 27). Decrease in HbA1c was
      observed irrespective of pre-existing therapy for diabetes: -2.3 +/- 1.5% for
      patients on diet alone; -0.6 +/- 1.3% for patients switched from sulfonylurea to
      study drug and -1.4 +/- 0.8% for patients on metformin in combination with study
      drug. FPG decreased significantly from 177.5 +/- 63.5 to 136.7 +/- 42.2 (p <
      0.001, n = 32) on gliclazide MR and not significant from 188.2 +/- 62.6 to 163.7
      +/- 67.9 (p = 0.059, n = 29) on gliclazide. Both treatments were very well
      tolerated with no major hypoglycaemic episodes requiring external assistance;
      only three patients experienced mild hypoglycaemic episodes. CONCLUSIONS: Once
      daily gliclazide MR showed a better trend in improving blood glucose control in
      comparison with gliclazide in type 2 diabetic Chinese patients irrespective of
      the pre-existing anti-diabetic treatment. The safety profiles of gliclazide MR
      and gliclazide were similar with a small number of patients having reported
      hypoglycaemic episodes. Once-daily dosing with gliclazide MR should improve
      patient compliance, an important factor in long-term glycaemic control.

PMID- 16448523
TI  - The serum levels of proinsulin and their relationship with IGFBP-1 in obese
      children.
AB  - AIM: Serum proinsulin (PI) levels were investigated in obese children to
      determine whether PI is a sensitive indicator of insulin resistance, as
      previously shown in adults with type 2 diabetes mellitus (DM), and to evaluate
      their relationship with insulin-like growth factor-binding protein-1 (IGFBP-1)
      known as a predictor of the development of cardiovascular disease in diabetic
      adults. SUBJECTS AND METHODS: Forty-two obese children without DM (age, 12.1 +/-
      1.5 year) and 42 age-matched control children were included in the study. The
      serum levels of PI, immunoreactive insulin (IRI), IGFBP-1 and free insulin-like
      growth factor-1 (IGF-1) were measured in the fasting state. RESULTS: The fasting
      levels of serum PI and IRI were significantly higher in obese children than in
      controls (PI, 10.5 +/- 6.8 vs. 5.6 +/- 2.0 pmol/l, p < 0.001; IRI, 72.0 +/- 41.8
      vs. 32.7 +/- 19.5 pmol/l, p < 0.001). Serum IGFBP-1 levels were significantly
      lower in obese children than in controls (37.7 +/- 24.6 vs. 76.3 +/- 26.5
      microg/l, p < 0.001). The ratio of PI to IRI (calculated as molar ratios) did not
      differ significantly between obese and control subjects (0.16 +/- 0.08 vs. 0.19
      +/- 0.11, p = 0.08). For the whole group, serum PI levels correlated positively
      with IRI and inversely with IGFBP-1 (IRI, r = 0.67, p < 0.001; IGFBP-1, r = 
      0.49, p < 0.001). Serum IGFBP-1 levels correlated inversely with both BMI and IRI
      (BMI, r = -0.73, p < 0.001; IRI, r = -0.60, p < 0.001). Multiple regression
      analysis revealed that the best predictive parameters for IGFBP-1 were BMI and PI
      (R2 = 0.57, p < 0.001 and p < 0.05, respectively). CONCLUSION: These findings
      suggest that fasting serum PI levels may be a better predictor than fasting
      insulin levels for the future development of type 2 DM and cardiovascular disease
      in obese children, and PI, in addition to insulin, contributes to the suppression
      of hepatic IGFBP-1 production.

PMID- 16448524
TI  - Differential effect of glimepiride and rosiglitazone on metabolic control of type
      2 diabetic patients treated with metformin: a randomized, double-blind, clinical
      trial.
AB  - AIM: Accumulating evidence suggests that combination therapy using oral
      antidiabetic agents with different mechanisms of action may be highly effective
      in achieving and maintaining target blood glucose levels. The aim of our study is
      to evaluate the differential effect on glucose and lipid parameters of the
      association between glimepiride plus metformin and rosiglitazone plus metformin
      in patients affected by type 2 diabetes and metabolic syndrome. METHODS: Patients
      were enroled, evaluated and followed at two Italian centres. We evaluated 99 type
      2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males
      and 24 females, aged 52 +/- 5 with glimepiride; 25 males and 23 females, aged 54
      +/- 4 with cglitazone). All were required to have been diagnosed as being
      diabetic for at least 6 months and did not have glycaemic control with diet and
      oral hypoglycaemic agents such as sulphonylureas or metformin, both to the
      maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day.
      We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a
      randomized, controlled, double-blind clinical study. We evaluated body mass index
      (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density
      lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and
      triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein
      B (Apo B)] during 12 months of this treatment. RESULTS: A total of 95 patients
      completed the study. Significant BMI decrease was observed at 12 months in
      glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well
      as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean
      fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p <
      0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma
      insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the
      baseline value in rosiglitazone group was observed. Furthermore, homeostasis
      model assessment index improvement was obtained only at 9 and 12 months (p < 0.05
      and p < 0.01 respectively) compared with the baseline value in rosiglitazone
      group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was
      present in glimepiride group after 12 months compared with the baseline values,
      and these variations were significant (p < 0.05) between groups. Of the 95
      patients who completed the study, 8.5% of patients in glimepiride group and 12.5%
      of patients in rosiglitazone group had side-effects (p = not significant). Four
      patients had transient side-effects in glimepiride group and six patients in
      rosiglitazone group. Altogether, we did not have statistically significant
      changes in transaminases. CONCLUSIONS: The rosiglitazone-metformin association
      significantly improve the long-term control of all insulin-resistance-related
      parameters in comparison with the glimepiride-metformin-treated group. On the
      other side, glimepiride treatment is associated to a slight improvement in
      cholesterolaemia, not observed in the rosiglitazone-treated patients.

PMID- 16448525
TI  - Prediction of response to sibutramine therapy in obese non-diabetic and diabetic
      patients.
AB  - BACKGROUND: Early weight loss is generally considered to predict long-term weight
      outcome in obese patients, and this is reflected in prescribing guidelines for
      antiobesity drugs. For example, the current prescribing guidelines for the
      antiobesity drug, sibutramine, indicate that if patients have not lost 2 kg (or 4
      lb) in the first 4 weeks of treatment with sibutramine 10 mg, the physician
      should re-evaluate the therapy, which may result in increasing the dose to 15 mg
      or discontinuation. This regimen may deny treatment to a large group of patients
      who might otherwise benefit, particularly patients with type 2 diabetes who often
      find it more difficult to lose weight than non-diabetic obese individuals.
      MATERIALS: We have re-analysed pooled data from seven randomized, controlled
      studies of sibutramine-induced weight loss and maintenance in which patients (n =
      928; 75% female) had taken sibutramine 10 or 15 mg continuously for 12 months, in
      order to determine the predictors of success in weight loss (defined as loss of
      at least 5% of initial body weight at Month 12) in both diabetic and non-diabetic
      patients. Sensitivity and specificity analyses were used to calculate optimal
      predictive values. RESULTS: In both diabetic and non-diabetic patients, weight
      loss of 4 kg at 3 months was identified as the optimal predictor for achieving at
      least 5% weight loss at 12 months. This target was associated with the best
      average values for sensitivity, specificity and accuracy, as well as high
      positive (78% vs. 84% for non-diabetics and 76% vs. 85% for diabetics, compared
      to existing guidelines target of 2 kg after 1 month treatment) and negative
      predictive values (63% vs. 71% for non-diabetics; 52% vs. 70% for diabetics).
      CONCLUSION: Sibutramine, in conjunction with diet and exercise, should be
      continued for at least 3 months (providing there are no adverse effects) to
      determine whether or not patients are likely to achieve a clinically valid
      outcome at 1 year. This highlights the need to ensure that regulatory
      restrictions reflect the needs of clinical practice.

PMID- 16448526
TI  - Does ethnic origin have an independent impact on hypertension and diabetic
      complications?
AB  - AIM: The morbidity and mortality from cardiovascular complications in diabetes
      reputedly differ with ethnicity. We have evaluated the prevalence of hypertension
      and vascular complications amongst Afro-Caribbean (AC), Caucasian (C) and Indo
      Asian (IA) ethnic subgroups of a district's diabetes population to estimate the
      impact of ethnic origin as an independent risk variable. METHODS: Of the 6485
      registered adult individuals, 6047 had ethnic data available and belonged to one
      of the three ethnic groups described (AC 9%, C 70% and IA 21%). Statistical
      analyses were performed using spss version 11.5. RESULTS: Results are presented
      as mean +/- s.d. or percentage. IAs were younger (AC 63 +/- 13, C 61 +/- 15 and
      IA 57 +/- 13 years), were less obese (body mass index 30 +/- 8, 29 +/- 9, 28 +/-
      6 kg/cm2) and had lower systolic blood pressure (155 +/- 25, 149 +/- 24, 147 +/-
      24 mmHg) and lower prevalence of hypertension (82%, 74% and 68%) compared with C,
      who had lower values than AC (all p < 0.01). Relative to C group, the AC group
      had higher prevalence of hypertension and microvascular complications but lower
      macrovascular disease burden, while the IA group had lower hypertension and
      macrovascular complications but with comparable microvascular disease burden
      [microvascular (51%, 44% and 46%; p < 0.01) and macrovascular (33%, 40% and 32%;
      p < 0.001)]. On logistic regression, this effect of ethnic origin on diabetic
      complications was found to be significant and independent of other risk
      variables. CONCLUSION: Hypertension and diabetic complication rates were
      different amongst ethnic subgroups. On logistic regression, it was found that the
      difference in distribution of age and diabetes duration largely accounted for
      this difference, although ethnic origin remained an independent risk factor.

PMID- 16448527
TI  - Subnormal energy expenditure: a putative causal factor in the weight gain induced
      by treatment of hyperthyroidism.
AB  - AIMS: To examine the causes of weight gain occurring as an adverse effect of
      treatment of hyperthyroidism. METHODS: We measured 24-h energy expenditure (EE),
      body composition and spontaneous physical activity (SPA) in eight patients before
      and 1 year after treatment of hyperthyroidism was initiated, and eight controls.
      RESULTS: One year after initiation of treatment thyrotropin was normalized,
      thyroid hormones had fallen to the lower end of the reference range and fat mass
      had increased by 3.5 kg (p < 0.001). Twenty-four hour EE adjusted for fat-free
      mass (FFM) was 15% higher in hyperthyroid patients before treatment than in
      controls (p = 0.003), and treatment decreased 24-h EE by 1.9 MJ/day (p = 0.001).
      After treatment, 24-h EE, adjusted for FFM, was similar to the controls. Multiple
      regression analyses showed that the suppressed EE could partly be attributed to
      an iatrogenic suppression of thyroid hormones, resulting in lower sleeping EE.
      Twenty-four hour SPA was normal in the hyperthyroid state, but decreased after
      treatment by 21% (p = 0.045), to a level not significantly different, but still
      below that of the controls. CONCLUSIONS: The study suggests that weight gain
      during treatment of hyperthyroidism might be due to subnormal levels of EE and
      SPA caused by a suppression of the thyroid hormone to a level in the lower end of
      the normal range.

PMID- 16448528
TI  - Protein kinase B/Akt signalling is required for palmitate-induced beta-cell
      lipotoxicity.
AB  - AIM: This study was conducted to clarify cell death and survival signals in
      pancreatic beta-cell lipotoxicity. METHODS: Rat insulinoma INS-1 cells, with or
      without expression of dominant-negative mutant of Akt (K179M), were cultured with
      palmitate (C16:0) or oleate (C18:1) and cell numbers were determined by 0.2%
      eosin dye exclusion assay. The Akt activity was determined by anti-3'-phospho
      inositide-dependent protein kinase (Akt)/protein kinase B (PKB) or anti-phospho
      Akt (Serine 473) immunoblotting, and nuclear protein nuclear factor-kB (NF
      kappaB)-binding activity was by supershift analysis. RESULTS: Twenty-four hours
      treatment with palmitate increased the INS-1 cell number at 0.1-0.2 mM but
      decreased the cell number at 0.5-1 mM. Oleate did not affect cell number at 0.1
      1.0 mM. Palmitate dose-dependently increased phosphorylation of 473th serine in
      Akt/PKB. The K179M form of Akt/PKB abolished palmitate-induced cell proliferation
      at the low dose and death at the high dose. Nuclear protein NF-kappaB binding was
      enhanced at 0.2 and 0.5 mM of palmitate but decreased at 1.0 mM. CONCLUSION:
      Results suggest that Akt/PKB signalling is involved in palmitate-induced cell
      death and survival of pancreatic beta cell.

PMID- 16448530
TI  - Thymus and T-lymphocyte development: what is new in the 21st century?

PMID- 16448531
TI  - Establishment and functioning of intrathymic microenvironments.
AB  - The thymus supports the production of self-tolerant T cells from immature
      precursors. Studying the mechanisms regulating the establishment and maintenance
      of stromal microenvironments within the thymus therefore is essential to our
      understanding of T-cell production and ultimately immune system functioning.
      Despite our ability to phenotypically define stromal cell compartments of the
      thymus, the mechanisms regulating their development and the ways by which they
      influence T-cell precursors are still unclear. Here, we review recent findings
      and highlight unresolved issues relating to the development and functioning of
      thymic stromal cells.

PMID- 16448532
TI  - Cellular and molecular events during early thymus development.
AB  - The thymic stromal compartment consists of several cell types that collectively
      enable the attraction, survival, expansion, migration, and differentiation of T
      cell precursors. The thymic epithelial cells constitute the most abundant cell
      type of the thymic microenvironment and can be differentiated into
      morphologically, phenotypically, and functionally separate subpopulations of the
      postnatal thymus. All thymic epithelial cells are derived from the endodermal
      lining of the third pharyngeal pouch. Very soon after the formation of a thymus
      primordium and prior to its vascularization, thymic epithelial cells orchestrate
      the first steps of intrathymic T-cell development, including the attraction of
      lymphoid precursor cells to the thymic microenvironment. The correct segmentation
      of pharyngeal epithelial cells and their subsequent crosstalk with cells in the
      pharyngeal arches are critical prerequisites for the formation of a thymus
      anlage. Mutations in several transcription factors and their target genes have
      been informative to detail some of the complex mechanisms that control the
      development of the thymus anlage. This review highlights recent findings related
      to the genetic control of early thymus organogenesis and provides insight into
      the molecular basis by which lymphocyte precursors are attracted to the thymus.

PMID- 16448533
TI  - Trafficking from the bone marrow to the thymus: a prerequisite for thymopoiesis.
AB  - T-cell development in the thymus requires periodic importation of hematopoietic
      progenitors from the bone marrow. Such thymus settling progenitors arise from
      hematopoietic stem cells (HSCs) that are retained in a specific bone marrow
      microenvironmental niche. Vacation of this niche is required for HSC
      proliferation and differentiation into downstream progenitors. In order to reach
      the thymus, progenitors must then be mobilized from bone marrow to blood.
      Finally, progenitors in blood must settle in the thymus. Here we review signals
      and molecular interactions that are likely to play a role in trafficking from the
      bone marrow to the thymus, focusing on how these interactions may regulate which
      progenitors physiologically contribute to thymopoiesis.

PMID- 16448534
TI  - Cyclical mobilization and gated importation of thymocyte progenitors in the adult
      mouse: evidence for a thymus-bone marrow feedback loop.
AB  - It has recently been observed, as in the fetal thymus, that the importation of
      hematogenous thymocyte progenitors by the adult thymus is a gated phenomenon,
      whereby saturating numbers of progenitors periodically enter the thymus and
      occupy a finite number of intrathymic niches. In addition, the mobilization of
      thymocyte progenitors from the bone marrow appears to be a cyclical process that
      coincides temporally with the periods of thymic receptivity (open gate). It is
      proposed that these events are coordinated by a thymus-bone marrow feedback loop
      in which a wave of developing triple negative (CD3- CD4- CD8-) thymocytes
      interacts with stromal cells in the stratified regions of the thymus cortex to
      sequentially induce the release of diffusible cytokines that regulate the
      production, mobilization, and recruitment of thymocyte progenitors. The likely
      components of this feedback loop are described here, as are the properties of the
      intrathymic vascular gates and niches for thymocyte progenitors. The cyclical
      production and release of thymocyte progenitors from the bone marrow is placed in
      the context of a general phenomenon of oscillatory feedback regulation involving
      all lymphohemopoietic cell lineages. Lastly, the question of whether the gated
      (as opposed to the continuous) entry of thymocyte progenitors is essential for
      normal thymocytopoiesis in adult life is discussed.

PMID- 16448535
TI  - Regulation of intrathymic T-cell development by Lunatic Fringe- Notch1
      interactions.
AB  - Intrathymic Notch1 signaling critically regulates T-lineage specification and
      commitment as well as T-cell progenitor survival and differentiation. Notch1
      activation is continuously required during progression of early CD4/CD8-double
      negative thymocytes to the CD4/CD8-double-positive stage. This developmental
      transition occurs as thymocytes migrate from the corticomedullary junction (CMJ)
      to the outer subcapsular zone (SCZ) of the thymus. Members of two families of
      structurally distinct Notch ligands, Delta-like 1 and Jagged-1, are expressed by
      cortical thymic epithelial cells, but it is not known which ligands are
      functionally required within the CMJ and SCZ microenvironmental niches. Our
      laboratory has investigated this question by genetically manipulating thymocyte
      expression of Lunatic Fringe (L-Fng), a glycosyltransferase that enhances
      sensitivity of Notch receptors to Delta-like ligands. This approach has revealed
      that low-threshold intrathymic Notch1 signals instruct multipotent thymus-seeding
      progenitors to suppress their B-cell potential and choose the T-cell fate. This
      strategy has also revealed that Delta-like Notch ligands are functionally
      limiting in both the CMJ and SCZ microenvironmental niches. Finally, we discuss
      our recent demonstration that L-Fng-mediated competition for Delta-like ligands
      is an important mechanism for regulating thymus size.

PMID- 16448536
TI  - T-cell development, doing it in a dish.
AB  - The thymus provides a unique environment for the development of T lymphocytes
      from bone marrow-derived progenitor cells. Several environmental factors have
      been identified that influence the development of T cells in the thymus. In
      particular, the Notch pathway has emerged as critical for the induction of T
      lineage commitment and differentiation. Until recently, however, the precise
      nature of the thymus-derived signals that drive T-cell development were unclear,
      and the only reliable in vitro culture system that supported T-cell
      differentiation required the use of thymus organ cultures. Here, we discuss
      recent advances in the identification of critical Notch receptor ligands that
      have facilitated the development of a simple in vitro model for the
      differentiation of T cells 'in a dish', providing an alternate approach for
      studying T lymphopoiesis.

PMID- 16448537
TI  - T-cell development: an extrathymic perspective.
AB  - The lymph nodes (LNs) harbor a cryptic T-lymphopoietic pathway that is
      dramatically amplified by oncostatin M (OM). OM-transgenic mice generate massive
      amounts of T lymphocytes in the absence of Lin(-)c-Kit(hi)IL-7Ralpha- lymphoid
      progenitors and of reticular epithelial cells. Extrathymic T cells that develop
      along the OM-dependent LN pathway originate from Lin(-)c-Kit(lo)IL-7Ralpha+
      lymphoid progenitors and are different from classic T cells in terms of turnover
      kinetics and function. Positive selection does not obey the same rules in the
      thymus and the LNs, where positive selection of developing T cells is supported
      primarily by epithelial and hematopoietic cells, respectively. Extrathymic T
      cells undergo enhanced homeostatic proliferation and thereby acquire some
      properties of memory T cells. Following antigen encounter, extrathymic T-cells
      initiate proliferation and cytokine secretion more readily than classic T cells,
      but their accumulation is limited by an exquisite susceptibility to apoptosis.
      Studies on in vitro and in vivo extrathymic T-cell development have yielded novel
      insights into the essence of a primary T-lymphoid organ. Furthermore, comparison
      of the thymic and OM-dependent extrathymic pathways shows how the division of
      labor between primary and secondary lymphoid organs influences the repertoire and
      homeostasis of T lymphocytes.

PMID- 16448538
TI  - Trafficking on serpentines: molecular insight on how maturating T cells find
      their winding paths in the thymus.
AB  - Maintenance of the peripheral T-cell pool throughout the life requires
      uninterrupted generation of T cells. The majority of peripheral T cells are
      generated in the thymus. However, the thymus does not contain hematopoietic
      progenitors with unlimited self-renewing potential, and continuous production of
      T cells requires importation of such progenitors from the bone marrow into the
      thymus. Thymus-homing progenitors enter the thymus and subsequently migrate
      throughout distinct intrathymic microenvironments while differentiating into
      mature T cells. At each step of this scheduled journey, developing thymocytes
      interact intimately with the local stroma, which allow them to proceed to the
      next stage of their differentiation and maturation program. Undoubtedly,
      thymocyte/stroma interactions are instrumental for both thymocytes and stroma,
      because only their ongoing interplay generates and maintains a fully operational
      thymus, able to guarantee unimpaired T-cell supply. Therefore, proper T-cell
      generation intrinsically involves polarized cell migration during both adult life
      and embryogenesis when the thymus primordium develops into a functional thymus.
      The molecular mechanisms controlling cell migration during thymus development and
      postnatal T-cell differentiation are beginning to be defined. This review focuses
      on recent data regarding the role of cell migration in both colonization of the
      fetal thymus and T-cell development during postnatal life in mice.

PMID- 16448539
TI  - Turning T-cell receptor beta recombination on and off: more questions than
      answers.
AB  - Successful V(D)J recombination at the T-cell receptor beta (Tcrb) locus is
      critical for early thymocyte development. The locus is subject to a host of
      regulatory mechanisms that impart a strict developmental order to Tcrb
      recombination events and that insure that Tcrb recombination occurs in an
      allelically excluded fashion. Progress has been made in the understanding of the
      cis-acting control of Tcrb locus chromatin structure and the extent to which such
      accessibility control can account for the developmental regulation of Tcrb
      recombination. However, recent studies in our laboratory and elsewhere have made
      it abundantly clear that accessibility control is only part of the story, and
      multiple additional mechanisms impact both the developmental activation and
      inactivation of locus recombination events. Here we evaluate our current
      understanding of developmental regulation at the Tcrb locus. We highlight the
      many unresolved issues and we discuss how recent concepts emerging from studies
      of other antigen receptor loci may (or may not) help to resolve these issues.

PMID- 16448540
TI  - ATM-dependent DNA damage surveillance in T-cell development and leukemogenesis:
      the DSB connection.
AB  - The immune system is capable of recognizing and eliminating an enormous array of
      pathogens due to the extremely diverse antigen receptor repertoire of T and B
      lymphocytes. However, the development of lymphocytes bearing receptors with
      unique specificities requires the generation of programmed double strand breaks
      (DSBs) coupled with bursts of proliferation, rendering lymphocytes susceptible to
      mutations contributing to oncogenic transformation. Consequently, mechanisms
      responsible for monitoring global genomic integrity must be activated during
      lymphocyte development to limit the oncogenic potential of antigen receptor locus
      recombination. Mutations in ATM (ataxia-telangiectasia mutated), a kinase that
      coordinates DSB monitoring and the response to DNA damage, result in impaired T
      cell development and predispose to T-cell leukemia. Here, we review recent
      evidence providing insight into the mechanisms by which ATM promotes normal
      lymphocyte development and protects from neoplastic transformation.

PMID- 16448541
TI  - Regulation of T-cell progenitor survival and cell-cycle entry by the pre-T-cell
      receptor.
AB  - Pre-T-cell receptor (pre-TCR) functions and the study of early thymocyte
      development continue to fascinate immunologists more than 10 years after the
      first description and cloning of the receptor. Although multiple reports have
      addressed several aspects of pre-TCR signaling and function, its ability to
      regulate diverse functions, including proliferation, survival, and allelic
      exclusion of the TCR-beta locus, remains an open question. What fascinates us is
      its central role in the fine balance between physiological differentiation and
      thymocyte transformation that leads to T-cell leukemia and lymphomas. In this
      review, we integrate pre-TCR signaling pathways and study their effects on the
      regulation of T-cell progenitor cell-cycle entry and cell survival. We also
      connect aberrant pre-TCR signaling to deregulated proliferation and apoptotic
      balances and thymocyte transformation.

PMID- 16448542
TI  - Strength of signal: a fundamental mechanism for cell fate specification.
AB  - How equipotent cells develop into complex tissues containing many diverse cell
      types is still a mystery. However, evidence is accumulating from different tissue
      systems in multiple organisms that many of the specific receptor families known
      to regulate cell fate decisions target conserved signaling pathways. A mechanism
      for preserving specificity in the cellular response that has emerged from these
      studies is one in which quantitative differences in receptor signaling regulate
      the cell fate decision. A signal strength model has recently gained support as a
      means to explain alphabeta/gammadelta lineage commitment. In this review, we
      compare the alphabeta/gammadelta fate decision with other cell fate decisions
      that occur outside of the lymphoid system to attain a better picture of the
      quantitative signaling mechanism for cell fate specification.

PMID- 16448543
TI  - Recent insights into the signals that control alphabeta/gammadelta-lineage fate.
AB  - During thymopoiesis, two major types of mature T cells are generated that can be
      distinguished by the clonotypic subunits contained within their T-cell receptor
      (TCR) complexes: alphabeta T cells and gammadelta T cells. Although there is no
      consensus as to the exact developmental stage where alphabeta and gammadelta T
      cell lineages diverge, gammadelta T cells and precursors to the alphabeta T-cell
      lineage (bearing the pre-TCR) are thought to be derived from a common CD4- CD8-
      double-negative precursor. The role of the TCR in alphabeta/gammadelta lineage
      commitment has been controversial, in particular whether different TCR isotypes
      intrinsically favor adoption of the corresponding lineage. Recent evidence
      supports a signal strength model of lineage commitment, whereby stronger signals
      promote gammadelta development and weaker signals promote adoption of the
      alphabeta fate, irrespective of the TCR isotype from which the signals originate.
      Moreover, differences in the amplitude of activation of the extracellular signal
      regulated kinase- mitogen-activated protein kinase-early growth response pathway
      appear to play a critical role. These findings will be placed in context of
      previous analyses in an effort to more precisely define the signals that control
      T-lineage fate during thymocyte development.

PMID- 16448544
TI  - At the crossroads: diverse roles of early thymocyte transcriptional regulators.
AB  - Transcriptional regulation of T-cell development involves successive interactions
      between complexes of transcriptional regulators and their binding sites within
      the regulatory regions of each gene. The regulatory modules that control
      expression of T-lineage genes frequently include binding sites for a core set of
      regulators that set the T-cell-specific background for signal-dependent control,
      including GATA-3, Notch/CSL, c-myb, TCF-1, Ikaros, HEB/E2A, Ets, and Runx
      factors. Additional regulators in early thymocytes include PU.1, Id-2, SCL, Spi
      B, Erg, Gfi-1, and Gli. Many of these factors are involved in simultaneous
      regulation of non-T-lineage genes, T-lineage genes, and genes involved in cell
      cycle control, apoptosis, or survival. Potential and known interactions between
      early thymic transcription factors such as GATA-3, SCL, PU.1, Erg, and Spi-B are
      explored. Regulatory modules involved in the expression of several critical T
      lineage genes are described, and models are presented for shifting occupancy of
      the DNA-binding sites in the regulatory modules of pre-Talpha, T-cell receptor
      beta (TCRbeta), recombinase activating genes 1 and 2 (Rag-1/2), and CD4 during T
      cell development. Finally, evidence is presented that c-kit, Erg, Hes-1, and
      HEBAlt are expressed differently in Rag-2(-/-) thymocytes versus normal early
      thymocytes, which provide insight into potential regulatory interactions that
      occur during normal T-cell development.

PMID- 16448546
TI  - Role of the transcription factor Th-POK in CD4:CD8 lineage commitment.
AB  - The molecular basis of CD4:CD8 lineage commitment, in particular the mechanism by
      which the precise correlation between lineage choice and T-cell receptor (TCR)
      specificity toward class I or II major histocompatibility complex is achieved,
      remains controversial. Both stochastic/selective and instructive models in
      various forms have been proposed to explain this correlation. The two main
      experimental approaches previously employed to elucidate this process have
      focused on the beginning and end of the process, i.e. the influence of TCR
      signaling and the alternate transcriptional control of the CD4 and CD8 loci
      during commitment. The recent finding that the transcription factor Th-POK is
      necessary and sufficient for CD4 commitment has now provided a direct entry point
      for studying the intracellular pathways that govern lineage commitment. Here, we
      review data leading to the identification and characterization of this factor and
      discuss the implications of these studies in the context of current models of
      lineage commitment.

PMID- 16448547
TI  - Commitment issues: linking positive selection signals and lineage diversification
      in the thymus.
AB  - The thymus is responsible for the production of CD4+ helper and CD8+ cytotoxic T
      cells, which constitute the cellular arm of the immune system. These cell types
      derive from common precursors that interact with thymic stroma in a T-cell
      receptor (TCR)-specific fashion, generating intracellular signals that are
      translated into function-specific changes in gene expression. This overall
      process is termed positive selection, but it encompasses a number of temporally
      distinct and possibly mechanistically distinct cellular changes, including rescue
      from apoptosis, initiation of cell differentiation, and commitment to the CD4+ or
      CD8+ T-cell lineage. One of the puzzling features of positive selection is how
      specificity of the TCR controls lineage commitment, as both helper and cytolytic
      T cells utilize the same antigen-receptor components, with the exception of the
      CD4 or CD8 coreceptors themselves. In this review, we focus on the signals
      required for positive selection, particularly as they relate to lineage
      commitment. Identification of genes encoding transcriptional regulators that play
      a role in T-cell development has led to significant recent advances in the field.
      We also provide an overview of nuclear factors in this context and, where known,
      how their regulation is linked to the same TCR signals that have been implicated
      in initiating and regulating positive selection.

PMID- 16448548
TI  - TCR and Notch signaling in CD4 and CD8 T-cell development.
AB  - The generation of CD4 and CD8 alphabeta T-cell lineages from CD4+ CD8+ double
      positive (DP) thymocyte precursors is a complex process initiated by engagement
      of major histocompatibility complex (MHC) by T-cell receptor (TCR) and
      coreceptor. Quantitative differences in TCR signaling induced by this interaction
      impose an instructional bias on CD4/CD8 lineage commitment that must be
      reinforced by MHC recognition and TCR signaling over subsequent selection steps
      in order for the thymocyte to progress and mature in the adopted lineage. Our
      studies show that the transmembrane receptor Notch plays a role in this process
      by modifying TCR signal transduction in DP thymocytes. In this review, we
      consider the functional relationship of TCR and Notch signaling pathways in the
      selection and specification of CD4 and CD8 T-cell lineages.

PMID- 16448549
TI  - Negative selection of the T-cell repertoire: where and when does it occur?
AB  - Because of the use of somewhat artificial models for the elucidation of negative
      selection [superantigen, T-cell receptor (TCR) transgenic mice], there is still
      considerable uncertainty at what stages of T-cell development negative selection
      can occur and whether it becomes manifest as developmental arrest, lineage
      diversion, or induction of apoptotic cell death. Here, experimental evidence is
      reviewed that excludes developmental arrest and lineage diversion as the sole
      mechanisms of negative selection. The data emphasize that both CD4+ CD8+ double
      positive cortical as well as semi-mature, single-positive, medullary thymocytes
      are targets of deletion in experimental models employing superantigen and TCR
      transgenic mice with premature as well as 'timely' onset of TCR expression.

PMID- 16448550
TI  - Central tolerance: good but imperfect.
AB  - T-cell development is a highly coordinated process that depends on interactions
      between thymocytes, thymic epithelium, and bone marrow (BM)-derived dendritic
      cells (DCs). Before entering the peripheral T-cell pool, thymocytes are subject
      to negative selection, a process that eliminates (or deletes) T cells with high
      affinity toward self-antigens and therefore promotes self-tolerance. These self
      antigens include those that are broadly expressed ubiquitous antigens and those
      whose expression is restricted to a few tissues, tissue-specific antigens (TSAs).
      Expression of TSAs in the thymus is mostly a property of medullary thymic
      epithelial cells (mTECs), and because these cells may be less capable than BM
      derived DCs at mediating negative selection to ubiquitous antigens, we
      investigated the roles of both of these cell types in tolerance to TSAs. Here, we
      review our studies in which we found that mTECs were competent mediators of
      negative selection to a subset of TSA-reactive T cells, while thymic DCs extend
      the range of TSA-reactive T cells that undergo negative selection by capturing
      TSAs from mTECs. In addition, we recently investigated the efficiency of central
      tolerance to TSA during ontogeny, and we report that this process was less
      efficient in neonates than adult animals.

PMID- 16448545
TI  - Progression of regulatory gene expression states in fetal and adult pro-T-cell
      development.
AB  - Precursors entering the T-cell developmental pathway traverse a progression of
      states characterized by distinctive patterns of gene expression. Of particular
      interest are regulatory genes, which ultimately control the dwell time of cells
      in each state and establish the mechanisms that propel them forward to subsequent
      states. Under particular genetic and developmental circumstances, the transitions
      between these states occur with different timing, and environmental feedbacks may
      shift the steady-state accumulations of cells in each state. The fetal transit
      through pro-T-cell stages is faster than in the adult and subject to somewhat
      different genetic requirements. To explore causes of such variation, this review
      presents previously unpublished data on differentiation gene activation in pro-T
      cells of pre-T-cell receptor-deficient mutant mice and a quantitative comparison
      of the profiles of transcription factor gene expression in pro-T-cell subsets of
      fetal and adult wildtype mice. Against a background of consistent gene
      expression, several regulatory genes show marked differences between fetal and
      adult expression profiles, including those encoding two basic helix-loop-helix
      antagonist Id factors, the Ets family factor SpiB and the Notch target gene
      Deltex1. The results also reveal global differences in regulatory alterations
      triggered by the first T-cell receptor-dependent selection events in fetal and
      adult thymopoiesis.

PMID- 16448551
TI  - A meta-analysis of hyperfractionated and accelerated radiotherapy and combined
      chemotherapy and radiotherapy regimens in unresected locally advanced squamous
      cell carcinoma of the head and neck.
AB  - BACKGROUND: Former meta-analyses have shown a survival benefit for the addition
      of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of
      hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy
      (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck.
      However, the publication of new studies and the fact that many older studies that
      were included in these former meta-analyses used obsolete radiation doses, CHX
      schedules or study designs prompted us to carry out a new analysis using strict
      inclusion criteria. METHODS: Randomised trials testing curatively intended RT (>
      or =60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx,
      hypopharynx, and larynx published as full paper or in abstract form between 1975
      and 2003 were eligible. Trials comparing RT alone with concurrent or alternating
      chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were
      analyzed according to the employed radiation schedule and the used CHX regimen.
      Studies comparing conventionally fractionated radiotherapy (CFRT) with either
      HFRT or AFRT without CHX were separately examined. End point of the meta-analysis
      was overall survival. RESULTS: Thirty-two trials with a total of 10 225 patients
      were included into the meta-analysis. An overall survival benefit of 12.0 months
      was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p
      < 0.001). Separate analyses by cytostatic drug indicate a prolongation of
      survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively,
      for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based,
      and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in
      overall survival was observed for AFRT in comparison to CFRT, a substantial
      prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT
      compared to CFRT (both without CHX). CONCLUSION: RT combined with simultaneous 5
      FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5
      FU with one of the other drugs results in a large survival advantage irrespective
      the employed radiation schedule. If radiation therapy is used as single modality,
      hyperfractionation leads to a significant improvement of overall survival.
      Accelerated radiation therapy alone, especially when given as split course
      radiation schedule or extremely accelerated treatments with decreased total dose,
      does not increase overall survival.

PMID- 16448552
TI  - A phase 1-2, prospective, double blind, randomized study of the safety and
      efficacy of Sulfasalazine for the treatment of progressing malignant gliomas:
      study protocol of [ISRCTN45828668].
AB  - BACKGROUND: The prognosis of patients suffering from WHO grade 3 and 4 astrocytic
      glioma remains poor despite surgery, radiation therapy and the use of current
      chemotherapy regimen. Indeed, the median survival of glioblastoma multiforme (WHO
      grade 4) patients is at best 14.6 month with only 26.5 percent of the patients
      still alive after 2 years and the median survival of anaplastic astrocytomas (WHO
      grade 3) is 19.2 month. Recent evidence suggests that the transcription factor NF
      kappaB is constitutively expressed in malignant gliomas and that its inhibition
      by drugs like Sulfasalazine may block the growth of astrocytic tumors in vitro
      and in experimental models of malignant gliomas. DESIGN: ULg_GBM_04/1 is a
      prospective, randomized, double blind single-center phase 1-2 study. A total of
      twenty patients with progressive malignant glioma despite surgery, radiation
      therapy and a first line of chemotherapy will be recruited and assigned to four
      dosage regimen of Sulfasalazine. This medication will be taken orally t.i.d. at a
      daily dose of 1.5-3-4 or 6 g, continuously until complete remission, evidence of
      progression or drug intolerance. Primary endpoints are drug safety in the setting
      of malignant gliomas and tumor response as measured according to MacDonald's
      criteria. An interim analysis of drug safety will be conducted after the
      inclusion of ten patients. The complete evaluation of primary endpoints will be
      conducted two years after the enrollment of the last patient or after the death
      of the last patient should this occur prematurely. DISCUSSION: The aim of this
      study is to evaluate the safety and efficacy of Sulfasalazine as a treatment for
      recurring malignant gliomas. The safety and efficacy of this drug are analyzed as
      primary endpoints. Overall survival and progression-free survival are secondary
      endpoint.

PMID- 16448553
TI  - Test-retest reproducibility of a food frequency questionnaire (FFQ) and estimated
      effects on disease risk in the Norwegian Women and Cancer Study (NOWAC).
AB  - BACKGROUND: The Norwegian Women and Cancer Study (NOWAC) is a national population
      based cohort study with 102 443 women enrolled at age 30-70 y from 1991 to 1997.
      The present study was a methodological sub-study to assess the test-retest
      reproducibility of the NOWAC food frequency questionnaire (FFQ), and to study how
      measurement errors in the data can affect estimates of disease risk. METHODS: A
      random sample of 2000 women aged 46-75 y was drawn from the cohort in 2002. A
      self-instructive health and lifestyle questionnaire with a FFQ section was mailed
      to the same subjects twice (test-retest), about three months apart, with a
      response rate of 75%. The FFQ was designed to assess habitual diet over the past
      year. We assess the reproducibility of single questions, food groups, energy, and
      nutrients with several statistical measures. We also demonstrate the method of
      regression calibration to correct disease risk estimates for measurement error.
      Alcohol intake (g/day) and high blood pressure (yes/no) is used in the example.
      RESULTS: For single foods there were some indications of seasonal reporting bias.
      For food groups and nutrients the reliability coefficients ranged from 0.5-0.8,
      and Pearson's r, Spearman's rs, and two intraclass correlation coefficients gave
      similar results. Although alcohol intake had relatively high reproducibility (r =
      0.72), odds ratio estimates for the association with blood pressure were
      attenuated towards the null value compared to estimates corrected by regression
      calibration. CONCLUSION: The level of reproducibility observed for the FFQ used
      in the NOWAC study is within the range reported for similar instruments, but may
      attenuate estimates of disease risk.

PMID- 16448554
TI  - Reliability and psychometric properties of the Greek translation of the State
      Trait Anxiety Inventory form Y: preliminary data.
AB  - BACKGROUND: The State-Trait Anxiety Inventory form Y is a brief self-rating scale
      for the assessment of state and trait anxiety. The aim of the current preliminary
      study was to assess the psychometric properties of its Greek translation.
      MATERIALS AND METHODS: 121 healthy volunteers 27.22 +/- 10.61 years old, and 22
      depressed patients 29.48 +/- 9.28 years old entered the study. In 20 of them the
      instrument was re-applied 1-2 days later. Translation and Back Translation was
      made. The clinical diagnosis was reached with the SCAN v.2.0 and the IPDE. The
      Symptoms Rating Scale for Depression and Anxiety (SRSDA) and the EPQ were applied
      for cross-validation purposes. The Statistical Analysis included the Pearson
      Correlation Coefficient and the calculation of Cronbach's alpha. RESULTS: The
      State score for healthy subjects was 34.30 +/- 10.79 and the Trait score was
      36.07 +/- 10.47. The respected scores for the depressed patients were 56.22 +/-
      8.86 and 53.83 +/- 10.87. Both State and Trait scores followed the normal
      distribution in control subjects. Cronbach's alpha was 0.93 for the State and
      0.92 for the Trait subscale. The Pearson Correlation Coefficient between State
      and Trait subscales was 0.79. Both subscales correlated fairly with the anxiety
      subscale of the SRSDA. Test-retest reliability was excellent, with Pearson
      coefficient being between 0.75 and 0.98 for individual items and equal to 0.96
      for State and 0.98 for Trait. CONCLUSION: The current study provided preliminary
      evidence concerning the reliability and the validity of the Greek translation of
      the STAI-form Y. Its properties are generally similar to those reported in the
      international literature, but further research is necessary.

PMID- 16448555
TI  - On single and multiple models of protein families for the detection of remote
      sequence relationships.
AB  - BACKGROUND: The detection of relationships between a protein sequence of unknown
      function and a sequence whose function has been characterised enables the
      transfer of functional annotation. However in many cases these relationships can
      not be identified easily from direct comparison of the two sequences. Methods
      which compare sequence profiles have been shown to improve the detection of these
      remote sequence relationships. However, the best method for building a profile of
      a known set of sequences has not been established. Here we examine how the type
      of profile built affects its performance, both in detecting remote homologs and
      in the resulting alignment accuracy. In particular, we consider whether it is
      better to model a protein superfamily using a single structure-based alignment
      that is representative of all known cases of the superfamily, or to use multiple
      sequence-based profiles each representing an individual member of the
      superfamily. RESULTS: Using profile-profile methods for remote homolog detection
      we benchmark the performance of single structure-based superfamily models and
      multiple domain models. On average, over all superfamilies, using a truncated
      receiver operator characteristic (ROC5) we find that multiple domain models
      outperform single superfamily models, except at low error rates where the two
      models behave in a similar way. However there is a wide range of performance
      depending on the superfamily. For 12% of all superfamilies the ROC5 value for
      superfamily models is greater than 0.2 above the domain models and for 10% of
      superfamilies the domain models show a similar improvement in performance over
      the superfamily models. CONCLUSION: Using a sensitive profile-profile method we
      have investigated the performance of single structure-based models and multiple
      sequence models (domain models) in detecting remote superfamily members. We find
      that overall, multiple models perform better in recognition although single
      structure-based models display better alignment accuracy.

PMID- 16448556
TI  - A novel surface protein of Trichomonas vaginalis is regulated independently by
      low iron and contact with vaginal epithelial cells.
AB  - BACKGROUND: Trichomonosis caused by Trichomonas vaginalis is the number one, non
      viral sexually transmitted disease (STD) that affects more than 250 million
      people worldwide. Immunoglobulin A (IgA) has been implicated in resistance to
      mucosal infections by pathogens. No reports are available of IgA-reactive
      proteins and the role, if any, of this class of antibody in the control of this
      STD. The availability of an IgA monoclonal antibody (mAb) immunoreactive to
      trichomonads by whole cell (WC)-ELISA prompted us to characterize the IgA
      reactive protein of T. vaginalis. RESULTS: An IgA mAb called 6B8 was isolated
      from a library of mAbs reactive to surface proteins of T. vaginalis. The 6B8 mAb
      recognized a 44-kDa protein (TV44) by immunoblot analysis, and a full-length cDNA
      clone encoded a protein of 438 amino acids. Southern analysis revealed the gene
      (tv44) of T. vaginalis to be single copy. The tv44 gene was down-regulated at
      both the transcriptional and translational levels in iron-depleted trichomonads
      as well as in parasites after contact with immortalized MS-74 vaginal epithelial
      cells (VECs). Immunofluorescence on non-permeabilized organisms confirmed surface
      localization of TV44, and the intensity of fluorescence was reduced after
      parasite adherence to VECs. Lastly, an identical protein and gene were present in
      Tritrichomonas foetus and Trichomonas tenax. CONCLUSION: This is the first report
      of a T. vaginalis gene (tv44) encoding a surface protein (TV44) reactive with an
      IgA mAb, and both gene and protein were conserved in human and bovine
      trichomonads. Further, TV44 is independently down-regulated in expression and
      surface placement by iron and contact with VECs. TV44 is another member of T.
      vaginalis genes that are regulated by at least two independent signaling
      mechanisms involving iron and contact with VECs.

PMID- 16448557
TI  - Enhancing energy and glucose metabolism by disrupting triglyceride synthesis:
      Lessons from mice lacking DGAT1.
AB  - Although the ability to make triglycerides is essential for normal physiology,
      excess accumulation of triglycerides results in obesity and is associated with
      insulin resistance. Inhibition of triglyceride synthesis, therefore, may
      represent a feasible strategy for the treatment of obesity and type 2 diabetes.
      Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that
      catalyze the final reaction in the known pathways of mammalian triglyceride
      synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin
      sensitivity and are protected against diet-induced obesity and glucose
      intolerance. These metabolic effects of DGAT1 deficiency result in part from the
      altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice
      have helped to provide insights into the mechanisms by which cellular lipid
      metabolism modulates systemic carbohydrate and insulin metabolism, and a better
      understanding of how DGAT1 deficiency enhances energy expenditure and insulin
      sensitivity may identify additional targets or strategies for the treatment of
      obesity and type 2 diabetes.

PMID- 16448558
TI  - A stochastic model of oncogene expression and the relevance of this model to
      cancer therapy.
AB  - BACKGROUND: Ablation of an oncogene or of the activity of the protein it encodes
      can result in apoptosis and/or inhibit tumor cell proliferation. Therefore, if
      the oncogene or set of oncogenes contributing maximally to a tumor cell's
      survival can be identified, such oncogene(s) are the most appropriate target(s)
      for maximizing tumor cell kill. METHODS AND RESULTS: A mathematical model is
      presented that describes cellular phenotypic entropy as a function of cellular
      proliferation and/or survival, and states of transformation and differentiation.
      Oncogenes become part of the cellular machinery, block apoptosis and
      differentiation or promote proliferation and give rise to new states of cellular
      transformation. Our model gives a quantitative assessment of the amount of
      cellular death or growth inhibition that result from the ablation of an
      oncogene's protein product. We review data from studies of chronic myelogenous
      leukemia and K562 cells to illustrate these principles. CONCLUSION: The model
      discussed in this paper has implications for oncogene-directed therapies and
      their use in combination with other therapeutic modalities.

PMID- 16448559
TI  - Female urogenital dysfunction following total mesorectal excision for rectal
      cancer.
AB  - BACKGROUND: The effect of Total Mesorectal Excision (TME) on sexual function in
      the male is well documented. However, there is little literature in female
      patients. The aim of this study was to review the pelvic autonomic nervous
      anatomy in the female and to perform a retrospective audit of urinary and sexual
      function in women following surgery for rectal cancer where TME had been
      performed. Urogenital dysfunction was assessed through interview and
      questionnaire. METHOD: Twenty-three questionnaires, eighteen returned, were sent
      to women with a mean age 65.5 yrs (range 34-86). All had undergone total
      mesorectal excision for rectal cancer between 1998-2001. Mean follow-up was 18.8
      months (range 3-35). RESULTS: Preoperatively 5/18 (28%) were sexually active,
      3/18 (17%) of patients described urinary frequency and nocturia and 7/18 (39%)
      described symptoms of stress incontinence prior to surgery. Postoperatively all
      sexually active patients remained active although all described some discomfort
      with penetration. Two of the patients sexually active described reduced libido
      secondary to the stoma. Postoperative urinary symptoms developed with 59%
      reporting the development of nocturia, 18% developed stress incontinence and one
      patient required a permanent catheter. Of those with symptoms, 80% persisted
      longer than three months from surgery. Symptoms were predominant in those
      patients with low rectal cancers, particularly those undergoing abdomino-perineal
      excision and in those who had previously undergone abdominal hysterectomy.
      CONCLUSION: The treatment of rectal cancer involves surgery to the pelvic floor.
      Despite nerve preservation this is associated with the development of worsening
      nocturia and stress incontinence. This is most marked in those patients who had
      previously undergone a hysterectomy. Further studies are warranted to assess the
      interaction with previous gynaecological surgery.

PMID- 16448560
TI  - Energy expenditures & physical activity in rats with chronic suboptimal
      nutrition.
AB  - BACKGROUND: Sub-optimally nourished rats show reduced growth, biochemical and
      physiological changes. However, no one has assessed metabolic rate adaptations in
      rats subjected to chronic suboptimal nutrition (CSN). In this study energy
      expenditure (EE; kcal/100 g body weight) and physical activity (PA; oscillations
      in weight/min/kg body weight) were assessed in rats subjected to three levels of
      CSN. RESULTS: Body weight gain was diminished (76.7 +/- 12.0 and 61.6 +/- 11.0 g)
      in rats fed 70 and 60% of the ad-libitum fed controls which gained more weight
      (148.5 +/- 32.3 g). The rats fed 80% gained weight similarly to controls (136.3
      +/- 10.5 g). Percent Fat-free body mass was reduced (143.8 +/- 8.7 and 142.0 +/-
      7.6 g) in rats fed 70 and 60% of ad-libitum, but not in those fed 80% (200.8 +/-
      17.5 g) as compared with controls (201.6 +/- 33.4 g). Body fat (g) decreased in
      rats fed 80% (19.7 +/- 5.3), 70% (15.3 +/- 3.5) and 60% (9.6 +/- 2.7) of ad
      libitum in comparison to controls (26.0 +/- 6.7). EE and PA were also altered by
      CSN. The control rats increased their EE and PA during the dark periods by 1.4 +/
      0.8 and 1.7 +/- 1.1 respectively, as compared with light the period; whereas CSN
      rats fed 80 and 70% of ad-libitum energy intake had reduced EE and PA during the
      dark periods as compared with the light period EE(7.5 +/- 1.4 and 7.8 +/- 0.6 vs.
      9.0 +/- 1.2 and 9.7 +/- 0.8; p < 0.05, respectively), PA(3.1 +/- 0.8 and 1.6 +/-
      0.4 vs. 4.1 +/- 0.9 and 2.4 +/- 0.4; p < 0.05) and RQ (0.87 +/- 0.04 and 0.85 +/-
      0.5; vs. 0.95 +/- 0.03 and 0.91 +/- 0.05 p < 0.05). In contrast, both light (7.1
      +/- 1.4) and dark period (6.2 +/- 1.0) EE and PA (3.4 +/- 0.9 and 2.5 +/- 0.5
      respectively) were reduced in rats fed 60% of ad-libitum energy intake.
      CONCLUSION: CSN rats adapt to mild energy restriction by reducing body fat, EE
      and PA mainly during the dark period while growth proceeds and lean body mass is
      preserved. At higher levels of energy restrictions there is decreased growth,
      body fat and lean mass. Moreover EE and PA are also reduced during both light and
      dark periods.

PMID- 16448561
TI  - Extra-curricular physical activity and socioeconomic status in Italian
      adolescents.
AB  - BACKGROUND: The relationship between physical activity and health status has been
      thoroughly investigated in several studies, while the relation between physical
      activity and socio-economic status (SES) is less investigated. The aim of this
      study was to measure the extra-curricular physical activity of adolescents
      related to the socio-economic status (SES) of their families. METHODS: The survey
      was carried out by submitting an anonymous questionnaire to junior high school
      students in the following Regions: Lazio, Abruzzo, Molise, Campania, Puglia,
      during the school year 2002-2003. Extra-curriculum physical activity was
      evaluated considering whether or not present and hours of activity weekly
      conducted. 2411 students agreed to participate in the study. RESULTS:
      Participants were 1121 males (46.5%) and 1290 females (53.5%), aged between 11
      and 17 years (median age: 12 years). 71.1% of the students reported to practice
      extra-curricular physical activity. Parents' educational levels and work
      activities play an important role in predicting students' physical activity, with
      the more remunerative activities and higher educational levels being more
      predictive. CONCLUSION: The results confirm the relationship between adolescents'
      physical activity and their families' SES. In particular, a positive relationship
      between participation in extra-curricular physical activity and their families
      high SES was found. These data will be useful for school administrators and for
      politicians in order to reduce the gap between adolescents from the least and
      most disadvantaged families.

PMID- 16448562
TI  - Effects of filtering by Present call on analysis of microarray experiments.
AB  - BACKGROUND: Affymetrix GeneChips are widely used for expression profiling of tens
      of thousands of genes. The large number of comparisons can lead to false
      positives. Various methods have been used to reduce false positives, but they
      have rarely been compared or quantitatively evaluated. Here we describe and
      evaluate a simple method that uses the detection (Present/Absent) call generated
      by the Affymetrix microarray suite version 5 software (MAS5) to remove data that
      is not reliably detected before further analysis, and compare this with filtering
      by expression level. We explore the effects of various thresholds for removing
      data in experiments of different size (from 3 to 10 arrays per treatment), as
      well as their relative power to detect significant differences in expression.
      RESULTS: Our approach sets a threshold for the fraction of arrays called Present
      in at least one treatment group. This method removes a large percentage of probe
      sets called Absent before carrying out the comparisons, while retaining most of
      the probe sets called Present. It preferentially retains the more significant
      probe sets (p < or = 0.001) and those probe sets that are turned on or off, and
      improves the false discovery rate. Permutations to estimate false positives
      indicate that probe sets removed by the filter contribute a disproportionate
      number of false positives. Filtering by fraction Present is effective when
      applied to data generated either by the MAS5 algorithm or by other probe-level
      algorithms, for example RMA (robust multichip average). Experiment size greatly
      affects the ability to reproducibly detect significant differences, and also
      impacts the effect of filtering; smaller experiments (3-5 samples per treatment
      group) benefit from more restrictive filtering (> or =50% Present). CONCLUSION:
      Use of a threshold fraction of Present detection calls (derived by MAS5) provided
      a simple method that effectively eliminated from analysis probe sets that are
      unlikely to be reliable while preserving the most significant probe sets and
      those turned on or off; it thereby increased the ratio of true positives to false
      positives.

PMID- 16448563
TI  - Sagittal jaw position in relation to body posture in adult humans--a
      rasterstereographic study.
AB  - BACKGROUND: The correlations between the sagittal jaw position and the cranio
      cervical inclination are described in literature. Only few studies focus on the
      sagittal jaw position and the body posture using valid and objective orthopaedic
      examination methods. The aim of this study was to test the hypothesis that
      patients with malocclusions reveal significant differences in body posture
      compared to those without (upper thoracic inclination, kyphotic angle, lordotic
      angle and lower lumbar inclination). METHODS: Eighty-four healthy adult patients
      (with a mean age = 25.6 years and ranging from 16.1 to 55.8 years) were examined
      with informed consent. The orthodontic examination horizontal overjet (distance
      between upper and lower incisors) was determined by using an orthodontic digital
      sliding calliper. The subjects were subdivided in respect of the overjet with the
      following results: 18 revealed a normal overjet (Class I), 38 had an increased
      overjet (Class II) and 28 had an reversed overjet (Class III). Rasterstereography
      was used to carry out a three-dimensional back shape analysis. This method is
      based on photogrammetry. A three-dimensional shape was produced by analysing the
      distortion of parallel horizontal white light lines projected on the patient's
      back, followed by mathematical modelling. On the basis of the sagittal profile
      the upper thoracic inclination, the thoracic angle, the lordotic angle and the
      pelvic inclination were determined with a reported accuracy of 2.8 degrees and
      the correlations to the sagittal jaw position were calculated by means of ANOVA,
      Scheffe and Kruskal-Wallis procedures. RESULTS: Between the different overjet
      groups, no statistically significant differences or correlations regarding the
      analysed back shape parameters could be obtained. However, comparing males and
      females there were statistically significant differences in view of the
      parameters 'lordotic angle' and 'pelvic inclination'. CONCLUSION: No correlations
      between overjet and variables of the thoracic, lordotic or the pelvic inclination
      could be observed.

PMID- 16448564
TI  - The RIN: an RNA integrity number for assigning integrity values to RNA
      measurements.
AB  - BACKGROUND: The integrity of RNA molecules is of paramount importance for
      experiments that try to reflect the snapshot of gene expression at the moment of
      RNA extraction. Until recently, there has been no reliable standard for
      estimating the integrity of RNA samples and the ratio of 28S:18S ribosomal RNA,
      the common measure for this purpose, has been shown to be inconsistent. The
      advent of microcapillary electrophoretic RNA separation provides the basis for an
      automated high-throughput approach, in order to estimate the integrity of RNA
      samples in an unambiguous way. METHODS: A method is introduced that automatically
      selects features from signal measurements and constructs regression models based
      on a Bayesian learning technique. Feature spaces of different dimensionality are
      compared in the Bayesian framework, which allows selecting a final feature
      combination corresponding to models with high posterior probability. RESULTS:
      This approach is applied to a large collection of electrophoretic RNA
      measurements recorded with an Agilent 2100 bioanalyzer to extract an algorithm
      that describes RNA integrity. The resulting algorithm is a user-independent,
      automated and reliable procedure for standardization of RNA quality control that
      allows the calculation of an RNA integrity number (RIN). CONCLUSION: Our results
      show the importance of taking characteristics of several regions of the recorded
      electropherogram into account in order to get a robust and reliable prediction of
      RNA integrity, especially if compared to traditional methods.

PMID- 16448565
TI  - The distribution of burden of dental caries in schoolchildren: a critique of the
      high-risk caries prevention strategy for populations.
AB  - BACKGROUND: The 'high-risk approach' is a commonly adopted strategy recommended
      for the prevention of dental caries in populations. The scientific basis for the
      strategy has been questioned. The objective of this study is to assess the
      contribution that children identified at 'high-risk' made towards the total of
      new caries lesions over a 4-year period, by analysing the distribution of new
      lesions per 100 children. METHODS: Data are from the National Preventive
      Dentistry Demonstration Programme (NPDDP) in the United States. The analyses
      identified the distribution of new carious lesions over a 4-year period in four
      groups of 7 year-old children who received differing preventive regimes. RESULTS:
      The majority of new lesions occurred in those children classified at lowest
      caries risk at baseline. Irrespective of the preventive regime adopted and the
      initial caries levels, children classified as 'highest risk' contributed less
      than 6% of the total number of new lesions developing over 4 years. CONCLUSION:
      These findings challenge the basis for the adoption of a high-risk strategy.

PMID- 16448566
TI  - Primary care and pattern of skin diseases in a Mediterranean island.
AB  - BACKGROUND: In Greece where primary health care services are not fully developed,
      patients with simple or minor conditions have to attend to hospitals to be
      treated. We analysed the data of patients with cutaneous disorders attending the
      tertiary referral hospital on the Island of Crete, with the aim to identify the
      most common conditions that patients complain of, in order to define the areas
      where the education of General Practitioners in Dermatology must focus. METHODS:
      All patients attending the Dermatology ambulatory office in the Emergency
      Department of the University General Hospital of Heraklion from January 2003 to
      December 2003 were included in this retrospective analysis. The medical records
      of the patients (history, physical examination and laboratory investigations)
      were analysed to ascertain the diagnosis and the management of cases. All
      patients were evaluated by qualified dermatologists. RESULTS: A total of 3715
      patients attended the Dermatology Clinic. Most patients were young adults in the
      age group 21-40 years (38.4%), and the male to female ratio was 1 to 1.2.
      Allergic skin diseases, mostly dermatitis and urticaria (35.7%) were the most
      common for attendance, followed by infectious diseases (26.1%) and insect bites
      (10.2%). Inflammatory and autoimmune disorders accounted for 7.9% of the cases.
      Pruritus of unknown origin was diagnosed in 6.3% of patients. Skin tumors were
      detected in 2.7%. The management of the vast majority of cases (85.0%) consisted
      of advice with or without a prescription, while only 4.8% of patients required
      admission. CONCLUSION: Allergic and infectious skin diseases were the most common
      cutaneous diseases in patients attending this tertiary University hospital, while
      the management of most patients did not require specialised care. On the basis of
      the present data, the training of primary health care providers in Dermatology
      should emphasize these common conditions, with the aim of improving primary care
      and alleviating the burden on hospital care.

PMID- 16448567
TI  - Preliminary evidence of mitochondrial dysfunction associated with post-infective
      fatigue after acute infection with Epstein Barr virus.
AB  - BACKGROUND: Acute infectious diseases are typically accompanied by non-specific
      symptoms including fever, malaise, irritability and somnolence that usually
      resolve on recovery. However, in some individuals these symptoms persist in what
      is commonly termed post-infective fatigue. The objective of this pilot study was
      to determine the gene expression correlates of post-infective fatigue following
      acute Epstein Barr virus (EBV) infection. METHODS: We followed 5 people with
      acute mononucleosis who developed post-infective fatigue of more than 6 months
      duration and 5 HLA-matched control subjects who recovered within 3 months.
      Subjects had peripheral blood mononuclear cell (PBMC) samples collected at
      varying time points including at diagnosis, then every 2 weeks for 3 months, then
      every 3 months for a year. Total RNA was extracted from the PBMC samples and
      hybridized to microarrays spotted with 3,800 oligonucleotides. RESULTS: Those who
      developed post-infective fatigue had gene expression profiles indicative of an
      altered host response during acute mononucleosis compared to those who recovered
      uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2
      (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F
      transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin,
      alpha 2), known to be regulated during EBV infection, were differentially
      expressed in post-infective fatigue cases. Several of the differentially
      expressed genes affect mitochondrial functions including fatty acid metabolism
      and the cell cycle. CONCLUSION: These preliminary data provide insights into
      alterations in gene transcripts associated with the varied clinical outcomes from
      acute infectious mononucleosis.

PMID- 16448568
TI  - Limited beta2-adrenoceptor haplotypes display different agonist mediated airway
      responses in asthmatics.
AB  - BACKGROUND: In vitro and some in vivo studies suggested that genetic haplotypes
      may have an impact on beta2-agonist mediated airway responses in asthmatics. Due
      to strong linkage disequilibrium the single nucleotide polymorphisms (SNPs) in
      the beta2-adrenoceptor gene result in only a limited number of haplotypes. We
      intended to evaluate the impact of beta2-adrenoceptor haplotypes on beta2-agonist
      mediated airway responses and the development of tolerance in mild to moderate
      asthmatics. METHODS: Patients were genotyped for the part of the beta2
      adrenoceptor gene with a known bearing on receptor function and regulation.
      Cumulative dose response curves of fenoterol versus PD20 methacholine and FEV1
      were constructed after 2 week treatment periods with either terbutaline or
      placebo in a double blind, randomised and cross-over design. Analysis of the dose
      response curves was based on a repeated measurement analysis of covariance.
      RESULTS: In our study population comprising 45 asthmatic patients, we found three
      limited allelic haplotypes, resulting in six different genotypes. Our data
      support the existence of differences between these six genotypes both in the
      shape of the dose response relationship of the beta2-adrenoceptor agonist
      fenoterol as well as in the propensity to develop tolerance for these effects by
      pre-treatment with terbutaline. However, this could only be substantiated for the
      endpoint PD20 methacholine. CONCLUSION: Between beta2-adrenoceptor genotypes
      differences exist both in baseline beta2-agonist induced airway responses as well
      as in the propensity to develop tolerance during maintenance beta2-agonist
      therapy. The net differences after two weeks of therapy are, however, of
      magnitudes that are unlikely to be of clinical significance.

PMID- 16448569
TI  - Psychosis among "healthy" siblings of schizophrenia patients.
AB  - BACKGROUND: Schizophrenia aggregates in families and accurate diagnoses are
      essential for genetic studies of schizophrenia. In this study, we investigated
      whether siblings of patients with schizophrenia can be identified as free of any
      psychotic disorder using only register information. We also analyzed the
      emergence of psychotic disorders among siblings of patients with schizophrenia
      during seven to eleven years of follow-up. METHODS: A genetically homogenous
      population isolate in north-eastern Finland having 365 families with 446 patients
      with a diagnosis of schizophrenia was initially identified in 1991 using four
      nationwide registers. Between 1998 and 2002, 124 patients and 183 siblings in 110
      families were contacted and interviewed using SCID-I, SCID-II and SANS. We also
      compared the frequency of mental disorders between siblings and a random
      population comparison group sample. RESULTS: Thirty (16%) siblings received a
      diagnosis of psychotic disorder in the interview. 14 siblings had had psychotic
      symptoms already before 1991, while 16 developed psychotic symptoms during the
      follow-up. Over half of the siblings (n = 99, 54%) had a lifetime diagnosis of
      any mental disorder in the interview. CONCLUSION: Register information cannot be
      used to exclude psychotic disorders among siblings of patients with
      schizophrenia. The high rate of emergence of new psychotic disorders among
      initially healthy siblings should be taken into account in genetic analysis.

PMID- 16448570
TI  - Very-low-carbohydrate diets and preservation of muscle mass.

PMID- 16448572
TI  - Incidence and prevalence of upper-extremity musculoskeletal disorders. A
      systematic appraisal of the literature.
AB  - BACKGROUND: A systematic appraisal of the worldwide incidence and prevalence
      rates of UEDs available in scientific literature was executed to gauge the range
      of these estimates in various countries and to determine whether the rates are
      increasing in time. METHODS: Studies that recruited at least 500 people,
      collected data by using questionnaires, interviews and/or physical examinations,
      and reported incidence or prevalence rates of the whole upper-extremity including
      neck, were included. RESULTS: No studies were found with regard to the incidence
      of UEDs and 13 studies that reported prevalence rates of UEDs were included. The
      point prevalence ranged from 1.6-53%; the 12-months prevalence ranged from 2.3
      41%. One study reported on the lifetime prevalence (29%). We did not find
      evidence of a clear increasing or decreasing pattern over time. The case
      definitions for UEDs used in the studies, differed enormously. Therefore, it was
      not possible to pool the data. CONCLUSION: There are substantial differences in
      reported prevalence rates on UEDs. Main reason for this is the absence of a
      universally accepted way of labelling or defining UEDs. If we want to make
      progress in this field, the first requirement is to agree on unambiguous
      terminology and classification of EUDs.

PMID- 16448573
TI  - Comparison of assessment techniques: plasma lipid and lipoproteins related to the
      metabolic syndrome.
AB  - BACKGROUND: The purpose of this investigation was to determine the influence of
      analytical method on reported concentrations of plasma lipids and lipoproteins,
      and to determine if there are clinical implications of any potential differences
      on identification of the metabolic syndrome dyslipidemia, CVD risk stratification
      and classification of LDL subclass phenotype. RESULTS: Plasma triglyceride (TG)
      concentrations were 1.09 +/- 0.06 and 1.17 +/- 0.06 mmol/L and plasma high
      density lipoprotein cholesterol (HDL-C) concentrations were 1.09 +/- 0.03 vs 1.19
      +/- 0.03 mmol/L (both p < 0.05) from 113 duplicate samples sent to two
      laboratories utilizing different lipid and lipoprotein analytical methods (LABS 1
      and 2, respectively). Plasma total cholesterol and low-density lipoprotein
      cholesterol (LDL-C) concentrations were also significantly different between
      laboratories. Spearman rho correlations indicate excellent agreement of TG and
      HDL-C determined by the two laboratories (r = 0.96, TG; r = 0.91, HDL-C, both p <
      0.001). Eleven vs. 14 individuals met the TG criteria and 70 vs. 48 met HDL-C
      metabolic syndrome criteria with LAB 1 and 2, respectively. Apoprotein B
      concentration (LAB 1) and LDL particle number (LAB 2) were highly correlated. (r
      = 0.92, P < 0.01). LAB 2 characterized more individuals as LDL pattern B
      phenotype, as compared to LAB 1 (30 vs. 14%, P < 0.05). CONCLUSION: Different
      plasma lipid and lipoprotein analytical techniques yield results which are highly
      correlated, yet significantly different, which suggests a consistent measurement
      difference. This difference has clinical implications, in that the proportion of
      individuals identified as meeting the metabolic syndrome dyslipidemia criteria,
      "at risk" based upon apo B or LDL particle number, and the LDL pattern B
      phenotype will differ based upon choice of analytical method.

PMID- 16448574
TI  - Antineoplastic effects of the DNA methylation inhibitor hydralazine and the
      histone deacetylase inhibitor valproic acid in cancer cell lines.
AB  - BACKGROUND: Among the epigenetic alterations occurring in cancer, DNA
      hypermethylation and histone hypoacetylation are the focus of intense research
      because their pharmacological inhibition has shown to produce antineoplastic
      activity in a variety of experimental models. The objective of this study was to
      evaluate the combined antineoplastic effect of the DNA methylation inhibitor
      hydralazine and the histone deacetylase inhibitor valproic acid in a panel of
      cancer cell lines. RESULTS: Hydralazine showed no growth inhibitory effect on
      cervical, colon, breast, sarcoma, glioma, and head & neck cancer cell lines when
      used alone. On the contrary, valproic acid showed a strong growth inhibitory
      effect that is potentiated by hydralazine in some cell lines. Individually,
      hydralazine and valproic acid displayed distinctive effects upon global gene over
      expression but the number of genes over-expressed increased when cells were
      treated with the combination. Treatment of HeLa cells with hydralazine and
      valproic acid lead to an increase in the cytotoxicity of gemcitabine, cisplatin
      and adriamycin. A higher antitumor effect of adriamycin was observed in mice
      xenografted with human fibrosarcoma cells when the animals were co-treated with
      hydralazine and valproic acid. CONCLUSION: Hydralazine and valproic acid, two
      widely used drugs for cardiovascular and neurological conditions respectively
      have promising antineoplastic effects when used concurrently and may increase the
      antitumor efficacy of current cytotoxic agents.

PMID- 16448571
TI  - Comprehensive comparative analysis of kinesins in photosynthetic eukaryotes.
AB  - BACKGROUND: Kinesins, a superfamily of molecular motors, use microtubules as
      tracks and transport diverse cellular cargoes. All kinesins contain a highly
      conserved approximately 350 amino acid motor domain. Previous analysis of the
      completed genome sequence of one flowering plant (Arabidopsis) has resulted in
      identification of 61 kinesins. The recent completion of genome sequencing of
      several photosynthetic and non-photosynthetic eukaryotes that belong to divergent
      lineages offers a unique opportunity to conduct a comprehensive comparative
      analysis of kinesins in plant and non-plant systems and infer their evolutionary
      relationships. RESULTS: We used the kinesin motor domain to identify kinesins in
      the completed genome sequences of 19 species, including 13 newly sequenced
      genomes. Among the newly analyzed genomes, six represent photosynthetic
      eukaryotes. A total of 529 kinesins was used to perform comprehensive analysis of
      kinesins and to construct gene trees using the Bayesian and parsimony approaches.
      The previously recognized 14 families of kinesins are resolved as distinct
      lineages in our inferred gene tree. At least three of the 14 kinesin families are
      not represented in flowering plants. Chlamydomonas, a green alga that is part of
      the lineage that includes land plants, has at least nine of the 14 known kinesin
      families. Seven of ten families present in flowering plants are represented in
      Chlamydomonas, indicating that these families were retained in both the flowering
      plant and green algae lineages. CONCLUSION: The increase in the number of
      kinesins in flowering plants is due to vast expansion of the Kinesin-14 and
      Kinesin-7 families. The Kinesin-14 family, which typically contains a C-terminal
      motor, has many plant kinesins that have the motor domain at the N terminus, in
      the middle, or the C terminus. Several domains in kinesins are present
      exclusively either in plant or animal lineages. Addition of novel domains to
      kinesins in lineage-specific groups contributed to the functional diversification
      of kinesins. Results from our gene-tree analyses indicate that there was
      tremendous lineage-specific duplication and diversification of kinesins in
      eukaryotes. Since the functions of only a few plant kinesins are reported in the
      literature, this comprehensive comparative analysis will be useful in designing
      functional studies with photosynthetic eukaryotes.

PMID- 16448575
TI  - A randomized, parallel study of the safety and efficacy of 45 mg primaquine
      versus 75 mg bulaquine as gametocytocidal agents in adults with blood
      schizonticide-responsive uncomplicated falciparum malaria [ISCRTN50134587].
AB  - BACKGROUND: The WHO recommends that adults with uncomplicated P. falciparum
      successfully treated with a blood schizonticide receive a single dose of
      primaquine (PQ) 45 mg as a gametocytocidal agent. An earlier pilot study
      suggested that 75 mg of bulaquine (BQ), of which PQ is a major metabolite, may be
      a useful alternate to PQ. METHODS: In a randomized, partial blind study, 90
      hospitalized adults with Plasmodium falciparum malaria that was blood
      schizonticide-responsive and a gametocytemia of > 55/microl within 3 days of
      diagnosis were randomized to receive single doses of either PQ 45 mg or BQ 75 mg
      on day 4. We assessed gametocytemia on days 8, 15, 22 and 29 and gametocyte
      viability as determined by exflagellation (2 degrees end point) on day 8.
      RESULTS: On day 8, 20/31 (65%) primaquine recipients versus 19/59 (32%) bulaquine
      recipients showed persistence of gametocytes (P = 0.002). At day 15 and beyond,
      all patients were gametocyte free. On day 8, 16/31 PQ and 7/59 BQ volunteers
      showed gametocyte viability (p = 0.000065). CONCLUSION: BQ is a safe, useful
      alternate to PQ as a Plasmodium falciparum gametocytocidal agent and may clear
      gametocytemia faster than PQ.

PMID- 16448576
TI  - Improving the sensitivity of the hop index in patients with an ACL deficient knee
      by transforming the hop distance scores.
AB  - BACKGROUND: The one leg hop for distance is one of the most commonly employed
      functional tests utilized in the evaluation of the ACL deficient and
      reconstructed patient. While the reliability of the hop test scores has been well
      established, validity studies have revealed low sensitivity rates in detecting
      functional limitations using the hop index (the ratio or percentage of limb
      performance). However, the impact of the inherent limitations associated with the
      hop index have not been investigated to date. One specific limitation relates to
      the impact of the differences in the underlying hop distance scores. Therefore,
      this pilot study set out to determine: 1) the impact that between limb
      differences in hop distance has on the sensitivity of the hop index in detecting
      functional limitations and; 2) whether a logarithmic transformation of the
      underlying hop distance scores improves the sensitivity of the hop index.
      METHODS: A cross sectional design involving the evaluation of one leg hop for
      distance performance in a consecutive sample of 10 ACL deficient males with an
      isolated ACL tear awaiting reconstructive surgery and nine gender, age-matched
      controls. RESULTS: In the ACL deficient, the hop index was associated with the
      distance hopped on the non-injured limb (r = -0.66, p = 0.04) but not on the
      injured limb. Transformation (logarithmic) of the hop distance scores and re
      calculation of the hop index using the transformed scores increased the
      sensitivity of the hop index in the detection of functional limitations from 20
      to 60% and 50 to 70% using the normal limb symmetry reference norms of > or = 85%
      and 90% respectively. CONCLUSION: The distance hopped on the non-injured limb is
      a critical factor in detecting functional limitations using the hop index in
      patients with an ACL deficient knee. Logarithmic transformation of the hop
      distance scores minimizes the effect of the arithmetic differences between limbs
      however; the sensitivity of the hop index in detecting abnormal limb symmetry
      remains low.

PMID- 16448578
TI  - Abstracts of the 2005 International Meeting of the Institute of Human Virology.
      Baltimore, Maryland, USA, 29 August-2 September 2005.

PMID- 16448577
TI  - Effect of insulin on small intestinal transit in normal mice is independent of
      blood glucose level.
AB  - BACKGROUND: Insulin is the drug of choice in the management of diabetes mellitus
      (DM). About 76 % of diabetic patients suffer from gastrointestinal (GI)
      disorders. Therapy of DM with insulin primarily involves lowering of elevated
      blood glucose levels. Hence, on any organ in addition to insulin's effect,
      hypoglycaemic effect also prevails. A systematic study exploring the effect of
      insulin on small intestinal transit in normal laboratory animals is lacking.
      Hence, in the present study, the possible effect of insulin with or without
      associated hypoglycaemia on small intestinal transit in normal mice was examined.
      RESULTS: Insulin in all the doses tested (2 mu, 2 m and 2 U/kg) elicited a
      significant acceleration of SIT. The lower doses of insulin (2 mu and 2 m U/kg)
      produced significant acceleration of SIT and were associated with normal blood
      glucose levels. However, the highest dose of insulin (2 U/kg) produced an
      acceleration of SIT that was associated with significant fall in blood glucose
      levels. Further, the 2 m and 2 U doses of insulin significantly elevated serum
      insulin and C-peptide levels. CONCLUSION: Insulin at the lowest dose produced an
      acceleratory effect on SIT that was independent of blood glucose and serum
      insulin levels in normal mice.

PMID- 16448579
TI  - Effects of acute topiramate dosing on methamphetamine-induced subjective mood.
AB  - Clinical studies have shown that topiramate, a sulphamate-substituted
      fructopyranose derivative, might be an efficacious treatment for alcohol
      dependence, smoking cessation within an alcohol-dependent population, and cocaine
      dependence. Mechanistically, topiramate's therapeutic effects have been
      hypothesized to be due to inhibition of cortico-mesolimbic dopamine function, the
      primary substrate that governs the acquisition, maintenance, and reinstatement of
      goal-directed behaviour towards seeking abused drugs. Predicated on this
      hypothesis, we tested in 10 methamphetamine-dependent individuals (three females)
      whether low- or high-dose (15 or 30 mg i.v.) methamphetamine-induced positive
      subjective effects and reinforcement can be antagonized by low- or high-dose (100
      or 200 mg orally) topiramate using a placebo-controlled, cross-over, factorial
      design. Methamphetamine administration was associated with orderly, prototypical,
      and significant increases on measures of stimulation, euphoria, craving, and
      reinforcement; however, some dysphoric symptoms also emerged. Topiramate alone
      showed a non-significant trend towards mild reductions in positive mood and
      reinforcement; yet topiramate appeared to accentuate the appreciation of
      methamphetamine-induced stimulation and euphoria significantly, but not craving
      or reinforcement. The experimental combination of topiramate and methamphetamine
      appeared to be safe and well tolerated, with few adverse events. Acute dosing
      with up to 200 mg topiramate appears to enhance, rather than attenuate, the
      positive subjective effects of methamphetamine. Perhaps this indicates a partial
      inhibition of methamphetamine's reinforcing effects. Thus, testing chronically
      administered or higher doses, or both, of topiramate would be necessary to
      determine conclusively whether or not it can attenuate the positive subjective
      and reinforcing effects of methamphetamine.

PMID- 16448580
TI  - Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine:
      in-vitro and in-vivo studies.
AB  - Clinical and preclinical studies have shown that the effect of citalopram on
      serotonin (5-HT) reuptake inhibition and its antidepressant activity resides in
      the S-enantiomer. In addition, using a variety of in-vivo and in-vitro paradigms,
      it was shown that R-citalopram counteracts the effect of escitalopram. This
      effect was suggested to occur via an allosteric modulation at the level of the 5
      HT transporter. Using in-vitro binding assays at membranes from COS-1 cells
      expressing the human 5-HT transporter (hSERT) and in-vivo electrophysiological
      and microdialysis techniques in rats, the present study was directed at
      determining whether R-citalopram modifies the action of selective serotonin
      reuptake inhibitors (SSRIs) known to act on allosteric sites namely escitalopram,
      and to a lesser extent paroxetine, compared to fluoxetine, which has no affinity
      for these sites. In-vitro binding studies showed that R-citalopram attenuated the
      association rates of escitalopram and paroxetine to the 5-HT transporter, but had
      no effect on the association rates of fluoxetine, venlafaxine or sertraline. In
      the rat dorsal raphe nucleus, R-citalopram (250 microg/kg i.v.) blocked the
      suppressant effect on neuronal firing activity of both escitalopram (100
      microg/kg i.v.) and paroxetine (500 microg/kg i.v.), but not fluoxetine (10 mg/kg
      i.v.). Interestingly, administration of R-citalopram (8 mg/kg i.p.) attenuated
      the increase of extracellular levels of 5-HT ([5-HT]ext) in the ventral
      hippocampus induced by both escitalopram (0.28 microM) and paroxetine (0.75
      microM), but not fluoxetine (10 microM). In conclusion, the present in-vitro and
      in-vivo studies show that R-citalopram counteracts the activity of escitalopram
      and paroxetine, but not fluoxetine, by acting at the allosteric binding site of
      the 5-HT transporter, either located in the dorsal raphe nucleus or post
      synaptically in the ventral hippocampus. This conclusion is strengthened by the
      observation that the inhibitory effect of fluoxetine, which has no stabilizing
      effect on the radioligand/hSERT complex, was not blocked by co-administration of
      R-citalopram.

PMID- 16448581
TI  - Thalamic D2 receptors in dementia with Lewy bodies, Parkinson's disease, and
      Parkinson's disease dementia.
AB  - Dementia with Lewy bodies (DLB) is characterized by progressive dementia with two
      of three core symptoms; Parkinsonism, visual hallucinations or disturbances of
      consciousness/fluctuating attention. Dementia in Parkinson's disease (PDD) has
      similar neuropsychiatric characteristics. Reduced nigrothalamic dopamine and
      altered thalamic D2 receptors may mediate some of the non-motor symptoms of DLB
      and PDD. The study aims were to ascertain whether thalamic D2 density was altered
      in Parkinson's disease (PD), PDD and DLB, and whether D2 density was related to
      core symptoms. Thalamic D2 receptor binding was measured by post-mortem
      autoradiography in 18 cases of DLB, 13 PDD, 6 PD and 14 normal elderly controls.
      Highest D2 density in control cases was in the intralaminar, midline, anterior
      and mediodorsal nuclei. In PD without dementia D2 binding was elevated above
      controls in all thalamic regions, significantly in reticular, laterodorsal,
      centromedian, ventral centromedian, parafascicular, paraventricular,
      ventroposterior, ventrolateral posterior, and ventrointermedius nuclei. Compared
      to controls, DLB cases with Parkinsonism (DLB+EPS) had significantly elevated D2
      receptor density in laterodorsal and ventrointermedius nuclei; PDD cases had
      significantly raised density in the ventrointermedius, and DLB cases without
      Parkinsonism (DLB-EPS) did not show increased D2 density in any areas. In DLB and
      PDD cases with disturbances of consciousness, cases treated with neuroleptics had
      higher D2 binding in all thalamic regions, significantly in the mediodorsal and
      ventrolateral posterior nuclei. D2 receptor binding did not vary with cognitive
      decline (MMSE) or visual hallucinations, but was significantly higher with
      increased extrapyramidal symptoms.

PMID- 16448582
TI  - Differential effects on prepulse inhibition of withdrawal from two different
      repeated administration schedules of amphetamine.
AB  - In this study, rats were tested in behavioural paradigms relevant to
      schizophrenia during withdrawal from two different administration schedules of
      amphetamine (Amph). One of the escalating administration schedules, which has
      been employed in previous studies, consisted of three daily injections for 6 d
      with increasing dosages from 1 to 5 mg/kg Amph (Esc-5) and was compared to a
      hitherto never examined escalating administration schedule [three injections per
      day for 6 d escalating from 1 to 8 mg/kg Amph (Esc-8)]. Control animals received
      an equivalent volume of saline (Sal) injections according to the same schedule.
      Whereas rats treated with Esc-5, as reported before, failed to show an effect on
      prepulse inhibition (PPI), the Esc-8-treated rats exhibited a long-lasting
      disruption of PPI in a drug-free state on days 6, 13 and 55 of withdrawal. The
      Amph-pretreated animals demonstrated a similar magnitude of behavioural
      sensitization following an Amph challenge on withdrawal day 58 irrespective of
      the administration schedule. To evaluate if the withdrawal from the two Amph
      schedules led to a change in brain monoamine levels, a subgroup of animals was
      neurochemically examined in post-mortem for eight parameters in seven brain
      regions on withdrawal day 55. Withdrawal from the Esc-8 schedule induced reduced
      dopamine levels in the caudate putamen. Only this neurochemical finding and the
      PPI attenuation differentiated the Esc-8 animals from the Esc-5 and Sal animals.
      These data suggest that, based on the endogenous sensitization hypothesis of
      schizophrenia, the persistent disruption of PPI observed in animals withdrawn
      from Esc-8 can be used as a valid animal model of specific symptoms of
      schizophrenic patients.

PMID- 16448583
TI  - The association between socioeconomic indicators and cardiovascular disease risk
      factors in Rio de Janeiro, Brazil.
AB  - The objective of this study was to analyse the association between socioeconomic
      indicators and cardiovascular disease risk factors in adult residents of Rio de
      Janeiro city, Brazil. Data were obtained by direct interview and physical
      examination in a population-based cross-sectional study in the city of Rio de
      Janeiro, 1995-96. Subjects were selected by two-stage random sampling and
      information was collected on socioeconomic, anthropometric and demographic
      characteristics, as well as on existing risk factors for cardiovascular disease.
      An index to express the risk of cardiovascular disease (CVD) was built, based on
      the presence of two or more of the following risk factors: overweight (measured
      by the body mass index, BMI), fat location (measured by the waist-hip ratio
      index, WHR), smoking, hypertension, sedentary lifestyle and alcohol consumption.
      The association between this risk index and the socioeconomic variables level of
      schooling, per capita income and residence location (slum vs non-slum) was
      evaluated through logistic regression models that controlled for the age of the
      subjects. Two separate models were built, according to the gender of the
      subjects. Complete data were collected for 1413 males and 1866 females over the
      age of 20 years (82% of the intended sample). In the studied population, a
      considerable prevalence of risk for CVD was found: 42.2% among males and 65.4%
      among females. For males, the socioeconomic and demographic indicators retained
      in the logistic model were age (OR 1.01, 95% CI 1.00-1.01), level of schooling
      (1.77, 95% CI 1.39-2.26) and per capita income (OR 0.77, 95% CI 0.61-0.97). For
      females, the indicators retained were age (OR 1.02, 95% CI 1.01-1.02) and level
      of schooling (OR 2.26, 95% CI 1.84-2.77). The findings indicate that
      cardiovascular disease risk is already an alarming problem in the urban
      populations of developing countries, and that educational level is the most
      important socioeconomic factor associated with its presence.

PMID- 16448584
TI  - Sexual behaviours and contraception among university students in Turkey.
AB  - The aim of this study was to evaluate the sexual attitudes and behaviours of
      university students. An anonymous questionnaire was administered to 550 final
      year university students aged 20-25 years in Izmir, Turkey. Male students opposed
      premarital sexual intercourse for both genders more than female students did. The
      frequency of sexual intercourse among male students (61.2%) was higher than that
      among female students (18.3%). The mean age of first sexual intercourse was lower
      among male than among female respondents. The rate of condom use at first sexual
      intercourse was 47.4%. The frequency of having two or more past sexual partners
      and masturbation was higher among males than females. It was found that there
      were culture-specific and gender-dependent differences in sexual attitudes and
      behaviours of the university students. These results may help in the planning of
      education and health policies in Turkey.

PMID- 16448585
TI  - In vitro and in vivo anthelmintic efficacy of plant cysteine proteinases against
      the rodent gastrointestinal nematode, Trichuris muris.
AB  - Extracts of plants, such as papaya, pineapple and fig, are known to be effective
      at killing intestinal nematodes that inhabit anterior sites in the small
      intestine, such as Heligmosomoides polygyrus. In this paper, we demonstrate that
      similar in vitro efficacy also occurs against a rodent nematode of the large
      intestine, Trichuris muris, and confirm that the cysteine proteinases present in
      the plant extracts are the active principles. The mechanism of action of these
      enzymes involved an attack on the structural proteins of the nematode cuticle,
      which was similar to that observed with H. polygyrus. However, not all plant
      cysteine proteinases were equally efficacious because actinidain, from the juice
      of kiwi fruit, had no detrimental effect on either the motility of the worms or
      the nematode cuticle. Papaya latex was also shown to significantly reduce both
      worm burden and egg output of mice infected with adult T. muris, demonstrating
      that enzyme activity survived passage to the caecum and was not completely
      inactivated by the acidity of the host's stomach or destroyed by the gastric or
      pancreatic proteinases. Thus, the cysteine proteinases from plants may be a much
      needed alternative to currently available anthelmintic drugs due to their
      efficacy and novel mode of action against different gastrointestinal nematode
      species.

PMID- 16448586
TI  - Professionalism and licensure--the debate continues.

PMID- 16448587
TI  - Pro: Licensure necessary in the clinical laboratory.
AB  - The myths surrounding the licensure of clinical laboratory personnel are
      numerous, but many licensure detractors skew the facts in an attempt to convince
      both laboratorians and the general public that licensure of lab personnel is
      unnecessary. In her argument in favor of national licensure, longtime laboratory
      manager Diana Mass presents her case that debunks many of the so-called truths
      surrounding the negative impact of licensure.

PMID- 16448589
TI  - Creating a safe and productive atmosphere for employees.

PMID- 16448588
TI  - Con: Licensure unnecessary in the clinical laboratory.
AB  - Those who argue in favor of licensure for clinical laboratory scientists have
      their priorities in order, but fail to recognize the realities that would ensue
      were national licensure to be instituted. Higher health-care costs, elimination
      of rural facilities, and licensure board fraud are all unintended, yet dangerous,
      consequences that could occur. In his argument against national licensure,
      laboratory director Jack Garon summarizes some of the most salient research done
      regarding licensure and presents his case why it is unnecessary in the clinical
      laboratory.

PMID- 16448590
TI  - It's not easy being green.

PMID- 16448591
TI  - Losing health insurance coverage: unjust or unfortunate?

PMID- 16448592
TI  - Supply chain management in the clinical laboratory.
AB  - Between 15 and 45 percent of a clinical laboratory's operating budget is spent on
      supplies. Given the size of this expenditure, laboratory managers must pay close
      attention to the supply chain and develop effective strategies to manage their
      inventory. Areas that need analysis include the carrying cost of supplies, the
      cost to generate a purchase order, methods to efficiently count supplies on hand,
      processes to ensure that lot number items are used before their expiration, and
      detailed analysis of the inventory. At the University of California-San Francisco
      Medical Center, we investigated options to manage our inventory and implemented a
      computerized system. The system required modifications to existing practices,
      which initially seemed unwieldy. However, after a relatively short learning
      curve, the improvement to operations has been significant, with a reduction in
      wasted reagents, fewer staff hours used to count supplies, and the ability to
      provide prompt analysis of the inventory for audits and discussions with
      administration. Focusing on the supply chain has allowed us to reduce inventory
      expenses by approximately 8 percent, reduce waste, given us a more focused
      understanding of our operations, and provided us with the ability to analyze our
      inventory easily.

PMID- 16448593
TI  - The makeover of the Lakeshore General Hospital laboratories.
AB  - This article describes the expansion and reorganization of a moderate-sized
      Canadian laboratory from Day One to "Live Day." The key factors to the success of
      this project were organized planning by the laboratory staff and the introduction
      of core lab theories, team building, and organized training sessions. The
      successful makeover resulted in improved turnaround time for STAT tests,
      especially those coming from the Emergency Unit. The efforts of the laboratory
      personnel toward the improvement of laboratory services, in spite of budget,
      human resources constraints, and resistance to change, are addressed.

PMID- 16448594
TI  - Should sexually transmitted disease clinics routinely offer serologic testing for
      genital herpes?

PMID- 16448595
TI  - Empiric antifungal therapy in neutropenic cancer patients.
AB  - Hematopoietic stem cell transplant recipients and those patients with acute
      leukemia are at greatest risk for invasive fungal infections particularly due to
      Candida and Aspergillus species during periods of profound neutropenia. Empiric
      antifungal therapy in persistently febrile neutropenic patients has been adopted
      as a standard of care. Antifungal therapeutic options include: amphotericin B,
      lipid formulations of amphotericin B, fluconazole, itraconazole, voriconazole,
      and caspofungin. Amphotericin B preparations offer a beneficial effect for
      survival, defervescence, and a decrease in breakthrough fungal infections. Lipid
      formulations of amphotericin B may provide beneficial effects over amphotericin B
      with regard to survival, treatment of baseline fungal infection, breakthrough
      fungal infection, and fewer discontinuations due to lack of efficacy.
      Amphotericin B compounds produce a trend for better outcomes in defervescence,
      treatment of baseline fungal infections, prevention of breakthrough infections,
      and avoidance of discontinuation compared with the azoles. Caspofungin is also
      effective. The optimal empiric antifungal agent and the precise time of
      initiation remain to be determined.

PMID- 16448596
TI  - How best to deal with endocarditis.
AB  - Infective endocarditis (IE) is an infection of the endocardial surface, usually
      involving heart valves and/or prosthetic intracardiac devices. Although much
      emphasis has been placed on antimicrobial prophylaxis prior to dental work to
      prevent IE, the evidence supporting this approach and its effectiveness are
      lacking. Resulting in valvular dysfunction, continuous bacteremia with
      constitutional features, embolic phenomena, and immune-mediated disease,
      diagnosis of IE requires careful history taking, physical examination, and
      utilization of echocardiography, blood work, and microbiologic tests. IE is
      uniformly fatal without effective therapy. Treatment for most cases requires
      prolonged courses of bactericidal antimicrobials in doses sufficient to penetrate
      vegetations and kill the microorganisms. Drug-resistant organisms, prosthetic
      intracardiac devices, comorbid illness, and valvular dysfunction often complicate
      therapy, necessitating a look towards adjunctive cardiac surgery. Better data (in
      the form of population-based surveillance and clinical trials) is beginning to
      impact the management of infective endocarditis.

PMID- 16448598
TI  - Parenteral artesunate for treatment of severe malaria.

PMID- 16448597
TI  - Community-associated methicillin-resistant Staphylococcus aureus: reconsideration
      of therapeutic options.
AB  - Methicillin resistance, long recognized as characteristic of nosocomial
      Staphylococcus aureus, has increasingly been identified in community-acquired
      strains in the past 15 years. The genotypes of community-associated methicillin
      resistant S. aureus (MRSA) are different from nosocomial strains, and unlike
      nosocomial strains, they have a distinctive methicillin-resistance chromosomal
      cassette (designated type IV), are usually susceptible to multiple classes of
      antimicrobials other than beta-lactams, carry a distinctive virulence factor (the
      Panton-Valentine leukocidin), cause mainly skin and soft tissue infection and
      less frequently, necrotizing pneumonia, and involve predominantly children and
      young adults. Outbreaks have been reported in certain segments of the population
      (eg, football players, wrestlers, prison inmates, and native people) that often
      do not have the established risk factors for MRSA. However, these strains have
      also caused infections likely acquired in an institutional health care setting.
      Delay in starting appropriate antibiotic therapy for severe infections caused by
      MRSA can be life-threatening. This requires a reconsideration of the empiric
      choice of an anti-staphylococcal beta-lactam for seriously ill patients with
      suspected community-associated S. aureus infections.

PMID- 16448599
TI  - Malaria: diagnosis and treatment of falciparum malaria in travelers during and
      after travel.
AB  - Plasmodium falciparum is responsible for most of the mortality in travelers
      related to imported malaria. Problems that occur during travel include the
      inaccuracy of a microscopic diagnosis of malaria, both false positives and false
      negatives, when ill travelers seek care while abroad. A false positive diagnosis
      can result in unnecessary parenteral injections that carry a risk of transmission
      of blood-borne pathogens, receipt of potentially dangerous drugs such as
      halofantrine, or receipt of fake, counterfeit drugs. Increased morbidity and
      mortality are associated with delays in diagnosis and initiation of prompt
      treatment for falciparum malaria. Availability of expert microscopy to confirm
      the diagnosis of malaria is limited. The presence of splenomegaly and
      thrombocytopenia are strongly associated with malaria and would justify empiric
      treatment. The availability of atovaquone-proguanil, a safe and well tolerated
      oral drug, should prompt a reconsideration of current treatment recommendations
      that discourage empiric treatment on clinical suspicion alone.

PMID- 16448600
TI  - Eosinophilia: causes and pathobiology in persons with prior exposures in tropical
      areas with an emphasis on parasitic infections.
AB  - Eosinophilia in patients exposed to tropical or subtropical environments is
      caused most commonly by helminth (worm) infections. Besides a detailed exposure
      history, the diagnostic approach must consider other infections and noninfectious
      causes of eosinophilia, as treatments for many of these disorders differ.

PMID- 16448602
TI  - Nipah virus: impact, origins, and causes of emergence.
AB  - Nipah virus is an emerging zoonotic pathogen that causes severe febrile
      encephalitis resulting in death in 40% to 75% of human cases. Nipah virus is
      considered a biosafety level-4 pathogen and is listed as a select agent with high
      risk for public health and security due to its high mortality rate in people and
      the lack of effective vaccines or therapies. The natural reservoir for Nipah
      virus and related members of the genus Henipavirus are fruit bats of the genus
      Pteropus. Nipah virus emerged in Malaysia in 1998 as a porcine neurologic and
      respiratory disease that spread to humans who had contact with live, infected
      pigs. Research reviewed in this paper suggests that anthropogenic factors,
      including agricultural expansion and intensification, were the underlying causes
      of its emergence. Nipah virus has caused five subsequent outbreaks between 2001
      and 2005 in Bangladesh. Here, it appears to have spilled over directly from bats
      to humans, and person-to-person transmission is evident suggesting a heightened
      public health risk.

PMID- 16448603
TI  - Diabetes, insulin resistance, and HIV.
AB  - The transformation of HIV infection into a chronically managed illness through
      the widespread use of highly active antiretroviral therapy has brought with it
      comorbid conditions such as increased risk of cardiovascular disease. Diabetes
      and insulin resistance have emerged as important comorbidities associated with
      HIV infection and the use of antiretroviral therapy. Significant inroads have
      been made towards understanding the etiology of insulin resistance and diabetes
      in association with HIV and highly active antiretroviral therapy, and there are
      also emerging data on the prevalence and incidence of this problem. The
      recognition and management of diabetes mellitus, insulin resistance, and related
      complications will be an important part of long-term health maintenance for HIV
      infected patients.

PMID- 16448601
TI  - Leptospirosis in the tropics and in travelers.
AB  - Leptospirosis, caused by spirochetes of the genus Leptospira, has increasingly
      been recognized to affect travelers and residents in tropical settings. A
      zoonotic disease, leptospirosis is transmitted to humans through environmental
      surface waters contaminated by the urine of chronically infected mammals. Outcome
      of infection varies, ranging from acute febrile illness (including self-resolving
      undifferentiated fever) to aseptic meningitis to a fulminant syndrome of
      jaundice, oliguric renal failure, pulmonary hemorrhage, and refractory shock.
      Hospitalized cases have mortality rates as high as 25%. A recent clinical trial
      showed that third-generation cephalosporin is as effective as doxycycline and
      penicillin in the treatment of acute disease. Doxycycline is effective in
      preventing leptospirosis in travelers. No protective vaccine is currently
      available.

PMID- 16448605
TI  - A shortened, 2-hour rifampin test: a useful tool in Gilbert's syndrome.
AB  - INTRODUCTION: Diagnosis of Gilbert's disease often involves unnecessary testing
      and patient anxiety. Rifampin test can support the diagnosis; it has been
      described in short series and lacks standardization in dose, collection times,
      result presentation and interpretation. Our objective was to compare the response
      to oral rifampin in a series of patients with Gilbert's disease, 2 and 4 h after
      drug administration. PATIENTS AND METHODS: Eighty-nine patients with Gilbert's
      disease (elevated total bilirubin with no hepatopathy or hemolysis) were
      recruited. After a basal blood collection, 900 mg rifampin were administered per
      os and new samples were drawn 2 and 4 h later. Total and esterified bilirubin
      were measured in every sample. Haptoglobin concentration was also analyzed.
      RESULTS: When expressed as relative increase with respect to basal values,
      variations observed 2 h after rifampin intake were all above 15%. A significant
      correlation (r = 0.902; p = 0.000) was found between relative increases 2 and 4 h
      after drug administration. No significant variations were found in haptoglobin
      concentrations. CONCLUSION: Rifampin test is useful in diagnosing Gilbert's
      disease, but variations in total bilirubin concentrations (basal and post
      rifampin) make that no absolute cut-off value can be used. Correlation between 2-
      and 4-h relative increases suggests that a shortened version could simplify the
      test.

PMID- 16448604
TI  - Renal disease in patients with HIV.
AB  - As survival continues to improve in the era of highly active antiretroviral
      therapy, kidney, liver, and cardiac disease have become increasingly important
      sources of mortality and morbidity in patients with HIV. The incidence of end
      stage renal disease in patients with HIV is projected to increase, and the
      incidence of earlier chronic kidney disease, acute renal failure, and electrolyte
      abnormalities is likely to be much higher than appreciated. Both acute and
      chronic kidney disease are more common in the setting of advanced HIV, hepatitis
      coinfection or liver disease, and medication toxicity. Close collaboration
      between nephrologists and infectious disease specialists is important to
      facilitate the identification, diagnosis, and management of acute and chronic
      kidney disease in patients with HIV. Recently published guidelines highlight the
      increased awareness of kidney disease in the infectious disease community and
      provide guidelines for the detection and management of chronic kidney disease in
      patients with HIV.

PMID- 16448606
TI  - [Surgical treatment of pancreatic and periampullary carcinoma in a specialized
      unit: a decade later].
AB  - INTRODUCTION: Results of surgical treatment for pancreatic and periampullary
      carcinoma have improved in recent years owing to several factors, particularly
      the concentration of these patients in specialised surgical units. MATERIAL AND
      METHODS: Retrospective-prospective comparative study of results in 2 groups of
      patients treated over 2 different periods of time and with different surgical
      policy: group A, which included 80 patients treated from 1982 to 1992 in a
      general surgery unit, and group B, which comprised 151 patients treated from 1998
      to 2003 in a specialised hepato-biliary-pancreatic surgery unit. RESULTS:
      Surgical treatment in patients of groups A and B, respectively, was: resection in
      20% and 53.6% and by-pass in 62.5% and 36.4%. Postoperative morbidity after
      resection was similar (75% vs 74.1%) but higher after by-pass in group B (41.8%
      vs 34%). Postoperative mortality after surgical resection and by-pass was 25% and
      14.1%, respectively, for group A and 3.7% and 16.3%, respectively, for group B.
      Mean survival for all patients was 7.0 +/- 7.1 months for group A and 14.1 +/-
      15.3 months for group B. Mean survival for patients with surgical resection was
      11.8 +/- 9.8 months and 18.7 +/- 15.8 months for groups A and B, respectively.
      CONCLUSIONS: Pancreatic and periampullary carcinoma should be surgically treated
      in specialised pancreatic surgery units in order to offer the best outcome to
      patients.

PMID- 16448607
TI  - [Lamivudine and adefovir resistance in a patient with HBeAg negative chronic
      hepatitis B].
AB  - We have studied a 49-year-old patient with a HBeAg-negative chronic hepatitis B
      in whom, after 34 months of treatment with lamivudine and associated with an
      increase in the serum hepatitis B virus (HBV) DNA, the lamivudine resistance
      mutations M204I and L180V were detected. Lamivudine was substituted for adefovir
      dipivoxil and after 16 months of treatment, in the course of a study to
      investigate hepatitis B genotypes, the adefovir resistance mutation N236T was
      detected. HBV viral load in this sample was 3 yen 10(7) UI/ml. Adefovir is
      considered as the alternative treatment when lamivudine resistance is detected.
      Appearance of resistance to adefovir is very unusual and in Spain, no case has
      been communicated yet. However, we must be aware of the adefovir resistance in
      patients who do not respond to adefovir and it must be confirmed with a
      resistance study, if possible.

PMID- 16448609
TI  - [Gastric food bezoar as a complication of bariatric surgery. Case report and
      review of the literature].
AB  - In the last few years bariatric surgery has become an excellent therapeutic
      alternative for the treatment of morbid obesity. Food bezoar as a cause for
      obstruction seems to be a very infrequent postoperative complication. It has only
      been published as anecdotal case reports. We describe a female patient with
      morbid obesity (weight, 131 kg; body mass index, 45) who underwent laparoscopic
      bariatric surgery (subtotal 95% gastrectomy with gastroyeyunoanastomosis in Roux
      Y) obtaining a significant weight reduction (51 kg) in the next few months post
      surgery. She developed a food bezoar in the gastric remnant as a late
      complication of surgery (13 months after bariatric surgery) and presented as a
      gastric outlet acute obstruction with persistent vomiting and satiety. The
      diagnosis and treatment was performed through an upper GI endoscopy. It is
      important to consider this complication in patients with persisting vomiting
      after this kind of surgery. In the near future we will probably have a
      significant amount of patients operated due to morbid obesity and we may see this
      kind of complication more frequently.

PMID- 16448608
TI  - [MALT lymphoma in a patient with Crohn's disease. A causal or incidental
      association?].
AB  - We present the case of a 79-year-old woman who had received a diagnosis of
      Crohn's disease 3 years previously and who developed a mucosa-associated lymphoid
      tissue (MALT) lymphoma of the right colon while undergoing treatment with
      mesalazine. The patient had not received immunosuppressive drugs or infliximab.
      The possible association between Crohn's disease and the development of
      intestinal lymphomas is analyzed. The incidence, pathogenic mechanisms,
      diagnostic strategy, treatment and prognosis of these neoplasms are described,
      mainly with reference to MALT lymphomas of the colon.

PMID- 16448610
TI  - [Recommendations on tuberculosis and treatment of inflammatory bowel disease with
      infliximab. 2006 update].

PMID- 16448611
TI  - [Consensus document on the use of granulocytapheresis in patients with
      inflammatory bowel disease].

PMID- 16448613
TI  - [The intestine as an inducer, target and amplifying organ in acute graft-versus
      host disease].

PMID- 16448612
TI  - [Hepatic stellate cells: it's role in normal and pathological conditions].
AB  - Hepatic fibrosis is a dynamic and sophisticatedly regulated wound healing
      response to chronic hepatocellular injury. This fibrotic process results from the
      accumulation of extracellular matrix (ECM) including collagen, proteoglycan, and
      adhesive glycoproteins which are principally produced by hepatic stellate cells
      (HSC), a mesenchymal cell type located between parenchymal cell plates and
      sinusoidal endothelial cells in the space of Disse. In physiological conditions,
      quiescent HSCs play important roles in the regulation of retinoid homeostasis and
      ECM remodeling by producing ECM components as well as metalloproteases and its
      inhibitor. However during hepatic fibrogenesis, HSCs are known to be activated or
      "transdifferentiated" to myofibroblast-like cells which play a pivotal role in
      ECM remodeling and hepatic blood flow regulation. Activation of HSC is now well
      established as the key process involved in the development of hepatic fibrosis.
      Both basic morphology and functions of HSCs in normal conditions and its role in
      pathological fibrosis will be discussed in this review.

PMID- 16448614
TI  - [Utility of covered self-expanding prostheses in benign gastroesophageal
      disease].

PMID- 16448615
TI  - [Mantle-cell lymphoma].

PMID- 16448616
TI  - [Use of glue and metal clips for endoscopic sealing of iatrogenic gastric
      perforation].

PMID- 16448617
TI  - [Dissecting hematoma of the esophagus: a rare complication of hemodialysis].

PMID- 16448618
TI  - [Ulcerative colitis and autoimmune hemolytic anemia].

PMID- 16448619
TI  - Analysis of RNA-protein interactions by a microplate-based fluorescence
      anisotropy assay.
AB  - Quantitative studies of RNA-protein interactions are quite cumbersome using
      traditional methods. We developed a rapid microplate-based fluorescence
      anisotropy (FA)/fluorescence polarization assay that works well, even with RNA
      probes >90 nucleotides long. We analyzed binding of RNA targets by
      vigilin/DDP1/SCP160p and by c-myc coding region instability determinant (CRD)
      binding protein, CRD-BP. Vigilin is essential for cell viability and functions in
      heterochromatin formation and mRNA decay. The CRD-BP stabilizes c-myc mRNA.
      Vigilin bound to a vitellogenin mRNA 3'-UTR probe with a two to three-fold lower
      affinity than to a Drosophila dodecasatellite ssDNA binding site and bound to the
      c-myc CRD with a two- to three-fold lower affinity than to the vitellogenin mRNA
      3'-UTR. Competition between vigilin and CRD-BP for binding to the CRD may
      therefore play a role in regulating c-myc mRNA degradation. We analyzed
      suitability of the microplate-based FA assay for high-throughput screening for
      small-molecule regulators of RNA-protein interactions. The assay exhibits high
      reproducibility and precision and works well in 384-well plates and in 5 microl
      to 20 microl samples. To demonstrate the potential of this assay for screening
      libraries of small molecules to identify novel regulators of RNA-protein
      interactions, we identified neomycin and H33342 as inhibitors of binding of
      vigilin to the vitellogenin mRNA 3'-UTR.

PMID- 16448620
TI  - Micro-scale open-tube capillary separations of functional proteins.
AB  - This article describes a novel technique whereby fully functional proteins or
      multiprotein complexes are efficiently extracted from biological samples to
      chemically derivatized walls of fused-silica open-tube capillary columns.
      Proteins are eluted with very high yields into elution volumes that are smaller
      in volume than the internal volume of the open-tube capillary column itself,
      thereby achieving 100-fold increases in target protein concentrations from
      starting samples of less than 1 ml. The open-tube capillary columns are designed
      for single use; combined with the physical and chemical characteristics of the
      open-tube capillary column, this provides exceptional purity to the eluted
      proteins. Affinity-based open-tube capillary columns are demonstrated here to
      purify, enrich, and maintain functionality for a monomeric and dimeric enzyme, a
      low-abundance HeLa nuclear complex, and a light-harvesting octadecameric membrane
      protein complex. The design of the open-tube capillary column allows for facile
      direction of the processed protein sample to any number of final detection
      techniques and is capable of generating final protein concentrations required for
      many structural biology experiments. The open-tube capillary columns are also
      characterized by exceptional ease of use. Current designs allow for up to 10 open
      tube capillary columns to be applied simultaneously with no fundamental
      impediments to even greater parallel operation.

PMID- 16448621
TI  - Benefits of prolonged gradient separation for high-performance liquid
      chromatography-tandem mass spectrometry quantitation of plasma total 15-series F
      isoprostanes.
AB  - The F(2)-isoprostanes are products of free-radical-induced oxidation of
      arachidonic acid (AA) that are stereoisomers of prostaglandin F(2alpha)
      (PGF(2alpha)). We describe a method for quantitation of several 15-series PGF
      isomers (15-PGFs) and AA by high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS-MS). Plasma samples were subjected to alkaline hydrolysis
      and acidified, and total (free + esterified) 15-PGFs and AA were extracted with
      organic solvents. The analytes were separated by gradient reverse-phase HPLC and
      detected by multiple reaction monitoring on a triple-quadrupole mass
      spectrometer, using deuterated internal standards for quantitation. The assay had
      a linear range of 1-40 pg of 8-iso-PGF(2alpha) on column and can quantify as
      little as 40 pg/mL (0.11 nM) in plasma. Outcomes significantly correlated (p <
      0.0001) with data obtained by gas chromatography-mass spectrometry GC-MS or
      enzyme-linked immunosorbent assay. All plasma 15-PGF isomers increased over time
      with in vitro cigarette smoke exposure and correlated (p < 0.0001) with each
      other. The same strong inter-15-PGF correlations were observed in plasma from
      healthy young adult subjects. The coefficients of variation of HPLC-MS-MS
      measurements (24-32%) were smaller than those obtained by GC-MS (53%). Thus, HPLC
      MS-MS potentially offers greater precision and allows quantitation of more
      compounds with simpler sample preparation than existing methods. Ours is the
      first validated quantitative assay using HPLC-tandem MS applied to plasma total
      15-PGFs.

PMID- 16448622
TI  - [Indications of laparoscopic general and digestive surgery. Evidence based
      guidelines of the French society of digestive surgery].

PMID- 16448623
TI  - Generation of specific antibodies and their use to characterize sex differences
      in four rat P450 3A enzymes following vehicle and pregnenolone 16alpha
      carbonitrile treatment.
AB  - The purpose of this study was to identify isozyme-specific antibodies and use
      them to determine the expression levels of four P450 3A enzymes in the livers of
      vehicle- and pregnenolone 16alpha-carbonitrile (PCN)-treated rats of both sexes,
      since previous work on mRNA levels has shown considerable sexual dimorphism.
      Using Western blot analysis with four isozyme-specific antibodies, we show that
      P450 3A1, 3A2, and 3A9 were expressed in vehicle-treated adult female rats at
      very low levels whereas P450 3A18 was not detected. PCN treatment of females
      strongly induced the expression of P450 3A1 in the livers with protein product
      increases of 214-, 3-, and 5-fold for P450 3A1, 3A2, and 3A9, respectively, and
      P450 3A18 was induced to 3.7 pmol/mg protein. In contrast, all four P450 3As were
      detected in livers of vehicle-treated males, in the order of 3A2 >> 3A18 > 3A9
      approximately = 3A1. The protein product increases induced by PCN treatment of
      male rats were 92-, 3-, 6-, and 16-fold for P450 3A1, 3A2, 3A9, and 3A18,
      respectively.

PMID- 16448625
TI  - Inhibition of interleukin-4 production in activated T cells via the
      downregulation of AP-1/NF-AT activation by N-lauroyl-D-erythro-sphingosine and N
      lauroyl-D-erythro-C20-sphingosine.
AB  - Allergic diseases are hypersensitivity disorders that are associated with the
      generation of specific immunoglobulin E (IgE) in response to environmental
      allergens. Interleukin (IL)-4, which is primarily produced by the CD4(+) T cells,
      is an important stimulus for the switching of the antibody isotype to IgE in both
      mice and humans. In a previous study, we demonstrated that ceramide derivatives
      coupled with a lauroyl group exerted strong inhibitory effects on IL-4 production
      in T cells. In this study, we attempted to characterize the mechanisms underlying
      the inhibition of IL-4 production in T cells. Two ceramide derivatives, N-lauroyl
      D-erythro-sphingosine and N-lauroyl-D-erythro-C(20)-sphingosine (hereafter
      abbreviated as LES and LECS, respectively), were shown to significantly inhibit
      the production of IL-4 in both primary CD4(+) T cells and EL4 T thymoma cells in
      a dose-dependent manner. LES and LECS also inhibited the activity of the IL-4
      gene promoter in EL4 cells transiently transfected with IL-4 gene promoter
      constructs, but this effect was impaired in EL4 cells that had been transfected
      with an IL-4 promoter construct deleted of a P4 site harboring the AP-1 and NF-AT
      binding sites. Furthermore, LES and LECS inhibited the DNA binding activities of
      both AP-1 and NF-AT transcription factors. In addition, LES and LECS were
      demonstrated to suppress PMA-stimulated PKC activity, although they exerted no
      significant effects on the protein levels of the conventional PKCs. These results
      indicate that the ceramides, LES and LECS, may inhibit the production of IL-4 in
      the activated T cells, via the downregulation of AP-1/NF-AT activation and PKC
      activity.

PMID- 16448624
TI  - Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits
      vascular smooth muscle cell regrowth after in vitro mechanical injury.
AB  - Vascular smooth muscle cell (SMC) proliferation plays an important role in the
      pathogenesis of atherosclerosis and post-angioplasty restenosis. Berberine is a
      well-known component of the Chinese herb medicine Huanglian (Coptis chinensis),
      and is capable of inhibiting SMC contraction and proliferation, yet the exact
      mechanism is unknown. We therefore investigated the effect of berberine on SMC
      growth after mechanic injury in vitro. DNA synthesis and cell proliferation assay
      were performed to show that berberine inhibited serum-stimulated rat aortic SMC
      growth in a concentration-dependent manner. Mechanical injury with sterile
      pipette tip stimulated the regrowth of SMCs. Treatment with berberine prevented
      the regrowth and migration of SMCs into the denuded trauma zone. Western blot
      analysis showed that activation of the MEK1/2 (mitogen-activated protein kinase
      kinase 1/2), extracellular signal-regulated kinase (ERK), and up-regulation of
      early growth response gene (Egr-1), c-Fos and Cyclin D1 were observed
      sequentially after mechanic injury in vitro. Semi-quantitative reverse
      transcription PCR assay further confirmed the increase of Egr-1, c-Fos, platelet
      derived growth factor (PDGF) and Cyclin D1 expression in a transcriptional level.
      However, berberine significantly attenuated MEK/ERK activation and downstream
      target (Egr-1, c-Fos, Cyclin D1 and PDGF-A) expression after mechanic injury in
      vitro. Our study showed that berberine blocked injury-induced SMC regrowth by
      inactivation of ERK/Egr-1 signaling pathway thereby preventing early signaling
      induced by injury in vitro. The anti-proliferative properties of berberine may be
      useful in treating disorders due to inappropriate SMC growth.

PMID- 16448626
TI  - Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in
      women with bipolar disorder.
AB  - BACKGROUND: Preliminary evidence suggests that valproate is associated with
      isolated features of polycystic ovarian syndrome (PCOS), while contradictory data
      support an association between epilepsy and PCOS. The development of PCOS
      features after initiation of valproate was therefore examined in women with
      bipolar disorder using a standardized definition of PCOS. METHODS: Three hundred
      women 18 to 45 years old with bipolar disorder were evaluated for PCOS at 16
      Systematic Treatment Enhancement for Bipolar Disorder sites. A comparison was
      made between the incidence of hyperandrogenism (hirsutism, acne, male-pattern
      alopecia, elevated androgens) with oligoamenorrhea that developed while taking
      valproate versus other anticonvulsants (lamotrigine, topiramate, gabapentin,
      carbamazepine, oxcarbazepine) and lithium. Medication and menstrual cycle
      histories were obtained, and hyperandrogenism was assessed. RESULTS: Among 230
      women who could be evaluated, oligoamenorrhea with hyperandrogenism developed in
      9 (10.5%) of 86 women on valproate and in 2 (1.4%) of 144 women on a nonvalproate
      anticonvulsant or lithium (relative risk 7.5, 95% confidence interval [CI] 1.7
      34.1, p = .002). Oligoamenorrhea always began within 12 months of valproate use.
      CONCLUSIONS: Valproate is associated with new-onset oligoamenorrhea with
      hyperandrogenism. Monitoring for reproductive-endocrine abnormalities is
      important when starting and using valproate in reproductive-aged women.
      Prospective studies are needed to elucidate risk factors for development of PCOS
      on valproate.

PMID- 16448627
TI  - Reflection impulsivity in current and former substance users.
AB  - BACKGROUND: Chronic drug use is associated with increased impulsivity, risky
      decision making, and impaired behavioral control, but the underlying mechanisms
      of this neurocognitive profile remain unclear. We investigated impulsive
      responding in the context of decision making, using a novel behavioral measure of
      reflection impulsivity: the tendency to gather and evaluate information before
      making a decision. METHODS: The Information Sampling Task was administered to
      current substance users dependent on amphetamines (n = 24) or opiates (n = 40),
      former users of amphetamines or opiates abstinent for at least 1 year (n = 24),
      and non-drug-using control subjects (n = 26). RESULTS: Current users of
      amphetamines and opiates sampled less information than control subjects and
      responded at a lower probability of making a correct response. Amphetamine- and
      opiate-dependent subjects did not differ. Reduced reflection was also apparent in
      the former substance users, who did not differ from the current users.
      Questionnaire ratings of impulsivity (on the Barratt Impulsivity Scale, version
      11) were also inflated in three groups of substance users but were not
      significantly correlated with performance on the behavioral task. CONCLUSIONS:
      Reduced reflection is suggested to represent a cognitive marker for substance
      dependence that does not recover with prolonged abstinence and is associated with
      multiple drugs of abuse.

PMID- 16448628
TI  - Brain penetration of the novel free radical trapping neuroprotectant NXY-059 in
      rats subjected to permanent focal ischemia.
AB  - The penetration of the free radical trapping neuroprotectant NXY-059 into the
      brain has been examined in rats subjected to permanent middle cerebral artery
      occlusion (pMCAO). NXY-059 (125 mg/kg bolus followed by 125 mg/kg/h) was infused
      for 4 h 45 min starting 15 min after right pMCAO or sham operation. At 5 h, there
      was a similar plasma total NXY-059 concentration (micromol/L) in both groups
      [sham: 623 +/- 44 (6); pMCAO: 605 +/- 43 (5)] and a similar drug concentration
      (nmol/g) in the right cortex [sham: 6.92 +/- 1.05 (6); pMCAO: 6.14 +/- 2.18 (6)].
      A subsequent experiment in normal rats, infusing NXY-059 at both a similar and
      higher concentration (252 mg/kg bolus and 252 mg/kg/h), demonstrated that the
      concentration of NXY-059 in cortex increased linearly with respect to the plasma
      concentration. These data demonstrate that NXY-059 does penetrate brain tissue in
      control animals and ischemic tissue of animals subjected to pMCAO.

PMID- 16448629
TI  - Manual response preparation and saccade programming are linked to attention
      shifts: ERP evidence for covert attentional orienting and spatially specific
      modulations of visual processing.
AB  - The premotor theory of attention claims that attentional shifts are triggered
      during response programming, regardless of which response modality is involved.
      To investigate this claim, event-related brain potentials (ERPs) were recorded
      while participants covertly prepared a left or right response, as indicated by a
      precue presented at the beginning of each trial. Cues signalled a left or right
      eye movement in the saccade task, and a left or right manual response in the
      manual task. The cued response had to be executed or withheld following the
      presentation of a Go/Nogo stimulus. Although there were systematic differences
      between ERPs triggered during covert manual and saccade preparation, lateralised
      ERP components sensitive to the direction of a cued response were very similar
      for both tasks, and also similar to the components previously found during cued
      shifts of endogenous spatial attention. This is consistent with the claim that
      the control of attention and of covert response preparation are closely linked.
      N1 components triggered by task-irrelevant visual probes presented during the
      covert response preparation interval were enhanced when these probes were
      presented close to cued response hand in the manual task, and at the saccade
      target location in the saccade task. This demonstrates that both manual and
      saccade preparation result in spatially specific modulations of visual
      processing, in line with the predictions of the premotor theory.

PMID- 16448631
TI  - Upregulation of the initiating step of the kynurenine pathway in postmortem
      anterior cingulate cortex from individuals with schizophrenia and bipolar
      disorder.
AB  - Upregulation of the kynurenine pathway has been associated with several
      etiologies of psychosis, an indication that increased levels of pathway
      intermediates might be involved in eliciting some psychotic features. In
      schizophrenia, tryptophan 2,3-dioxygenase (TDO2) was previously identified in
      postmortem frontal cortex as the enzyme likely responsible for the reported
      increase in pathway activity in the brain. For this follow-up study of postmortem
      anterior cingulate gyrus, we have found evidence of increased TDO2 activity in
      schizophrenia at three different levels of regulation: mRNA, protein, and
      metabolic product. The results were unaffected by neuroleptic status or smoking
      history. To make the distinction between mental disorders with psychosis and
      those without, this study included patients with bipolar disorder and major
      depression. Compared to the control group, the HPLC, RT-PCR, and
      immunohistochemistry results show significant elevation of (1) kynurenine in
      schizophrenia (1.9-fold, P = 0.02), and in bipolar disorder (1.8-fold, P = 0.04),
      primarily in the bipolar subgroup with psychosis (2.1-fold, P = 0.03); (2) TDO2
      mRNA in schizophrenia (1.7-fold; P = 0.049); and (3) the immunohistochemistry
      values for the density of TDO2-positive white matter glial cells in schizophrenia
      (P = 0.01) and in major depression (P = 0.03) as well as the density and
      intensity of glial cells (in both gray and white matter) stained for TDO2 in
      bipolar disorder (P = 0.02). Unlike the results for schizophrenia and bipolar
      disorder, the increase in TDO2 protein in the major depression group was not
      associated with an increase in kynurenine concentration.

PMID- 16448630
TI  - Involvement of GABAergic modulation of antinociception induced by morphine
      microinjected into the ventrolateral orbital cortex.
AB  - Previous studies have shown that microinjection of morphine into the prefrontal
      ventrolateral orbital cortex (VLO) produces antinociception. The current study
      examined whether gamma-aminobutyric acid (GABA) containing neurons in the VLO
      were involved in this antinociception. Under light anesthesia, the GABA(A)
      receptor antagonist bicuculline and picrotoxin or agonist muscimol and THIP was
      microinjected into the VLO in non-morphine-treated (control) and morphine-treated
      (microinjection into the VLO) rats. Noxious heat-evoked tail flick (TF) latencies
      (TFLs) were measured in all of these groups of rats every 5 min. Bicuculline or
      picrotoxin (100, 200, 500 ng in 0.5 microl) depressed the TF reflex in a dose
      related fashion. A smaller dose (100 ng) of bicuculline or picrotoxin
      microinjected into VLO significantly enhanced the VLO morphine-evoked inhibition
      of the TF reflex. In contrast, administration of muscimol (250 ng) or THIP (1.0
      microg) significantly attenuated the morphine-induced antinociception in the VLO
      morphine-treated rats. These results suggest that the GABA(A) receptor is
      involved in the modulation of VLO morphine-induced antinociception, and provide a
      behavioral support for the hypothesis that morphine may directly inhibit the
      GABAergic inhibitory interneurons leading to indirect activation of the
      descending antinociceptive pathway through a disinhibitory effect on the VLO
      output neurons and depression of the nociceptive inputs at the spinal cord level.

PMID- 16448632
TI  - Is it the primetime for endoglin (CD105) in the clinical setting?

PMID- 16448633
TI  - Granulocyte colony-stimulating factor (G-CSF) accelerates reendothelialization
      and reduces neointimal formation after vascular injury in mice.
AB  - OBJECTIVE: Neointimal formation following percutaneous coronary intervention
      (PCI), termed restenosis, limits therapeutic revascularization. Since
      reendothelialization is one of the determinant factors for the development of
      neointimal formation, we examined the effects of granulocyte colony-stimulating
      factor (G-CSF) on reendothelialization and neointimal formation after vascular
      injury in mice. METHODS AND RESULTS: Wire-mediated vascular injury was produced
      in the femoral artery of C57BL/6 mice. G-CSF pretreatment significantly
      accelerated reendothelialization and decreased neointimal formation following
      vascular injury; however, this inhibitory effect of G-CSF was diminished when G
      CSF was started following the injury. Flow cytometry analysis revealed that G-CSF
      treatment increased the number of endothelial progenitor cells (EPCs: CD34+/Flk
      1+) in the peripheral circulation. Vascular injury was also produced in 2 types
      of mice whose bone marrow was replaced with that of enhanced green fluorescent
      protein- and Tie2/LacZ-transgenic mice. In the reendothelialized artery of these
      mice, few bone marrow-derived EPCs were detected. Furthermore, G-CSF treatment
      reduced the serum level of interleukin (IL)-6. CONCLUSION: G-CSF treatment
      accelerated reendothelialization and decreased neointimal formation following
      vascular injury, although there was little contribution of bone marrow-derived
      EPCs to the reendothelialization of the artery. These results suggest that G-CSF
      pretreatment has a therapeutic potential for prevention of restenosis following
      PCI.

PMID- 16448634
TI  - Improved cardiac gene transfer by transcriptional and transductional targeting of
      adeno-associated viral vectors.
AB  - OBJECTIVE: Vectors based on recombinant adeno-associated virus 2 (AAV-2) are a
      promising tool for cardiac gene transfer. However, potential therapeutic
      applications need to consider the predominant transduction of the liver once AAV
      2 vectors enter the systemic circulation. We therefore aimed to increase
      efficiency and specificity of cardiac vector delivery by combining
      transcriptional and cell surface targeting. METHODS: For analysis of
      transcriptional targeting, recombinant AAV vectors were generated harboring a
      luciferase reporter gene under control of the cytomegalovirus (CMV) promoter or
      the 1.5-kb cardiac myosin light chain promoter fused to the CMV immediate-early
      enhancer (CMV(enh)/MLC1.5). Luciferase activities were determined in
      representative organs three weeks after intravenous injection of the vector into
      adult mice. Transductional targeting was studied using luciferase-reporter
      constructs crosspackaged into capsids of AAV serotypes 1 to 6 and modified AAV-2
      capsids devoid of binding their primary receptor heparan sulfate proteoglycan.
      RESULTS: Intravenous injections of AAV-2 vectors harboring the CMV(enh)/MLC1.5
      promoter enabled a specific and 50-fold higher reporter gene expression in left
      ventricular myocardium of adult mice compared to vectors containing the CMV
      promoter. Comparison of AAV-2 vector genomes crosspackaged into capsids of AAV-1
      to -6 showed that AAV-1, -4, -5, and -6 capsids increased cardiac transduction
      efficiency by about 10-fold. However, transduction of other organs such as the
      liver was also increased after systemic administration. In contrast, AAV-2-based
      vectors with ablated binding to their primary receptor heparan sulfate
      proteoglycan enabled a significantly increased efficiency of cardiac gene
      transfer and reduced transduction of the liver. CONCLUSIONS: Combining
      transcriptional targeting by the CMV(enh)/MLC1.5 promoter and AAV vectors devoid
      of binding the AAV-2 primary receptor results in an efficient cardiac gene
      transfer with a significantly reduced hepatic transduction.

PMID- 16448635
TI  - Ligand triggers of classical preconditioning and postconditioning.
AB  - The cardioprotection afforded by ischemic preconditioning (IPC) and ischemic
      postconditioning (PC) are receptor mediated. In this review, we will focus on the
      major ligand classes and receptors that contribute to IPC and PC-induced
      cardioprotection. Ligand classes discussed include adenosine, bradykinin,
      opioids, erythropoietin, adrenergics and muscarinics. The cardioprotective
      therapeutic window of each ligand class will also be summarized, with particular
      focus as to whether ligands are protective when administered at or close to the
      time of reperfusion. Information will primarily be directed at studies in which
      infarct size reduction is the gold standard to assess the efficacy of IPC and PC.
      Myocardial stunning is a less robust endpoint for assessing cardioprotection and
      the use of this endpoint is only limited to studies with human tissue where
      infarct size assessment is not possible. Receptor cross-talk between ligands and
      the common signaling pathways involved for these ligands will also be briefly
      discussed.

PMID- 16448636
TI  - Neuroprotective effect of the stearic acid against oxidative stress via
      phosphatidylinositol 3-kinase pathway.
AB  - Stearic acid is a long-chain saturated fatty acid consisting of 18 carbon atoms
      without double bonds. In the present study, we reported the neuroprotective
      effects and mechanism of stearic acid on cortical or hippocampal slices insulted
      by oxygen-glucose deprivation, NMDA or hydrogen peroxide (H(2)O(2)) in vitro.
      Different types of models of brain slice injury in vitro were developed by 10 min
      of oxygen/glucose deprivation, 0.5 mM NMDA or 2 mM H(2)O(2), respectively. After
      30 min of preincubation with stearic acid (3-30 microM), cortical or hippocampal
      slices were subjected to oxygen-glucose deprivation, NMDA or H(2)O(2). Then the
      tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride
      (TTC) method. Population spikes were recorded in randomly selected hippocampal
      slices. Stearic acid (3-30 microM) dose-dependently protected brain slices from
      oxygen-glucose deprivation, NMDA and H(2)O(2) insults. Its neuroprotective effect
      against H(2)O(2) insults can be completely blocked by wortmannin (inhibitor of
      PI3K) and partially blocked by H7 (inhibitor of PKC) or genistein (inhibitor of
      TPK). Treatment of cortical or hippocampal slices with 30 microM stearic acid
      resulted in a significant increase in PI3K activity at 5, 10, 30 and 60 min.
      These observations reveal that stearic acid can protect cortical or hippocampal
      slices against injury induced by oxygen-glucose deprivation, NMDA or H(2)O(2),
      and its neuroprotective effects are via phosphatidylinositol 3-kinase dependent
      mechanism.

PMID- 16448637
TI  - Effectiveness of activated charcoal and equilibrium dialysis in removing Asian,
      American, Siberian and Indian ginseng from human serum.
AB  - BACKGROUND: Ginsengs are used by the general population worldwide and toxicity of
      various ginsengs has been reported. We studied the effectiveness of activated
      charcoal and in vitro equilibrium dialysis for removal of Asian, American,
      Siberian and Indian ginseng from human serum by measuring digoxin-like
      immunoreactivity using the fluorescence polarization immunoassay. METHODS: 1xPBS
      (phosphate buffered saline) or drug free serum pool was supplemented with Asian,
      American, Siberian or Indian ginseng extract in amount expected in overdose. The
      aliquots of supplemented buffer or serum pool were treated with activated
      charcoal (15 or 50 mg of activated charcoal/ml of buffer/serum) for 5, 10, 20 and
      30 min and digoxin-like immunoreactivities were compared with the original
      specimens. Other drug free serum pools were also supplemented with various
      ginsengs and then passed through a small column packed with activated charcoal or
      subjected to in vitro equilibrium dialysis against phosphate buffer at pH 7.4.
      RESULTS: Complete removal of digoxin-like immunoreactivity from buffer solution
      or serum pool supplemented with various ginsengs can be achieved by treatment
      with activated charcoal. Moreover, when serum pools supplemented with various
      ginsengs were passed through columns packed with activated charcoal, we observed
      complete removal of digoxin-like immunoreactivity. In addition, significant
      removal of digoxin-like immunoreactivity was observed when serum pools
      supplemented with ginsengs were subjected to equilibrium dialysis for 24 h.
      CONCLUSIONS: Removal of digoxin-like immunoreactivity from buffer solution or
      serum due to the presence of ginsengs can be achieved by treatment with activated
      charcoal in vitro but complete removal of digoxin-like activity from serum is not
      possible even after 24 h of equilibrium dialysis.

PMID- 16448638
TI  - The oxidative modification hypothesis of atherosclerosis: the comparison of
      atherogenic effects on oxidized LDL and remnant lipoproteins in plasma.
AB  - A tremendous number of articles on oxidized LDL (Ox-LDL) and scavenger receptor
      in macrophage have been published since Steinberg proposed Ox-LDL hypothesis as
      the major cause of atherosclerosis. This hypothesis has provided strong support
      for the efficacy of LDL lowering drugs, indicating that lowering LDL means
      lowering Ox-LDL in vivo. This manuscript proposed a new oxidative modification
      hypothesis that remnant lipoproteins determined as remnant-like lipoprotein
      particles (RLP), not LDL are the major oxidized lipoproteins in plasma, resulting
      from the plasma concentration of these oxidized lipoproteins. Remnant
      lipoproteins may play a pivotal role for the initiation of atherosclerosis via
      lectin-like oxidized LDL receptor-1 (LOX-1) in endothelial cells. Isolated
      remnant lipoproteins were found to be oxidized or susceptible to be oxidized in
      plasma, not necessary to be further oxidized in vitro as Ox-LDL. High similarity
      of proatherogenic and proinflammatory properties of isolated Ox-LDL and remnant
      lipoporteins have been reported and predicted the presence of similar oxidized
      phospholipids in both lipoproteins as bioactive components. These results suggest
      the possibility that reducing plasma remnant lipoproteins rather than LDL should
      be the target for hyperlipidemic therapy especially in patients with metabolic
      syndrome for the prevention of endothelial dysfunction in the initiation of
      atherosclerosis.

PMID- 16448639
TI  - Influence of glutathione S-transferase A1 polymorphism on the pharmacokinetics of
      busulfan.
AB  - BACKGROUND: High-dose oral busulfan is used for myeloablative chemotherapy before
      hematopoietic stem-cell transplantation. Fatal adverse effects or relapse may
      occur with excess or insufficient busulfan exposure. Glutathione S-transferase
      (GST) A1, whose genetic polymorphism in its promoter region has been reported, is
      responsible for busulfan metabolism. We investigated the polymorphism of GSTA1 on
      busulfan pharmacokinetics. METHODS: Blood samples (6 or 7 points) were taken from
      patients receiving high-dose oral busulfan (approximately 1 mg/kg every 6 h) on
      Doses 1 and 5. Pharmacokinetic parameters were calculated from plasma busulfan
      concentration. RESULTS: Twelve patients were enrolled in this study. Nine
      patients were genotyped as wildtype (GSTA1*A/*A), and 3 as heterozygous variants
      (GSTA1*A/*B). At Dose 5, the heterozygous group had significantly lower
      elimination constant (0.176+/-0.038 vs. 0.315+/-0.021 h-1; P=0.008) and clearance
      corrected by bioavailability (0.118+/-0.013 vs. 0.196+/-0.011 l/h/kg; P=0.004),
      and significantly higher mean plasma busulfan concentration (1344+/-158 vs. 854+/
      44 ng/ml; P=0.001) than the wildtype. CONCLUSIONS: This is the first report on
      the significant influence of GSTA1 polymorphism on busulfan elimination. This may
      account for the large inter-individual variance in busulfan pharmacokinetics, and
      with more information confirming our study, busulfan high-dose therapy may be
      optimized by GSTA1 genotyping in advance.

PMID- 16448640
TI  - Determination of visual figure and ground in dynamically deforming shapes.
AB  - Figure/ground assignment - determining which part of the visual image is
      foreground and which background - is a critical step in early visual analysis,
      upon which much later processing depends. Previous research on the assignment of
      figure and ground to opposing sides of a contour has almost exclusively involved
      static geometric factors - such as convexity, symmetry, and size - in non-moving
      images. Here, we introduce a new class of cue to figural assignment based on the
      motion of dynamically deforming contours. Subjects viewing an animated, deforming
      shape tended to assign figure and ground so that articulating curvature extrema -
      i.e., "hinging" vertices - had negative (concave) contour curvature. This
      articulating-concavity bias is present when all known static cues to
      figure/ground are absent or neutral in each of the individual frames of the
      animation, and even seems to override a number of well-known static cues when
      they are in opposition to the motion cue. We propose that the phenomenon reflects
      the visual system's inbuilt expectations about the way shapes will deform -
      specifically, that deformations tend to involve rigid parts articulating at
      concavities.

PMID- 16448641
TI  - Eye movements of monkey observers viewing vocalizing conspecifics.
AB  - Primates, including humans, communicate using facial expressions, vocalizations
      and often a combination of the two modalities. For humans, such bimodal
      integration is best exemplified by speech-reading - humans readily use facial
      cues to enhance speech comprehension, particularly in noisy environments. Studies
      of the eye movement patterns of human speech-readers have revealed, unexpectedly,
      that they predominantly fixate on the eye region of the face as opposed to the
      mouth. Here, we tested the evolutionary basis for such a behavioral strategy by
      examining the eye movements of rhesus monkeys observers as they viewed vocalizing
      conspecifics. Under a variety of listening conditions, we found that rhesus
      monkeys predominantly focused on the eye region versus the mouth and that
      fixations on the mouth were tightly correlated with the onset of mouth movements.
      These eye movement patterns of rhesus monkeys are strikingly similar to those
      reported for humans observing the visual components of speech. The data therefore
      suggest that the sensorimotor strategies underlying bimodal speech perception may
      have a homologous counterpart in a closely related primate ancestor.

PMID- 16448642
TI  - Xenopus Dead end mRNA is a localized maternal determinant that serves a conserved
      function in germ cell development.
AB  - Germ plasm formation is considered to define the first step in germ cell
      development. Xenopus Dead end represents a germ plasm specific transcript that is
      homologous to the previously characterized zebrafish dead end, which is required
      for germ cell migration and survival. XDead end mRNA localizes to the vegetal
      pole of Xenopus oocytes; in contrast to all other known germ plasm associated
      transcripts in Xenopus, XDead end is transported via the late transport pathway,
      suggesting a different mode of germ plasm restriction. Vegetal localization in
      the oocyte is achieved via a localization element mapping to a 251 nucleotide
      element in the 3'-UTR. This RNA sequence binds to a set of proteins
      characteristic for the late localization pathway and to one additional protein of
      38 kDa. Inhibition of XDead end translation in Xenopus embryos results in a loss
      of primordial germ cells at tadpole stages of development. Early specification
      events do not seem to be affected, but the primordial germ cells fail to migrate
      dorsally and eventually disappear. This phenotype is very similar to what has
      been observed in the zebrafish, indicating that the role of XDead end in germ
      cell development has been conserved in evolution.

PMID- 16448643
TI  - A qualitative review of housing hazard assessment protocols in the United States.
AB  - While the general link between substandard housing and poor health has received
      increased attention recently, there are currently no widely accepted standardized
      protocols to assess and remediate multiple housing-related health hazards. This
      paper compares several protocols that assess housing health hazards, including
      the Hazard Assessment and Reduction Program, the American Healthy Homes Survey,
      the Public Housing Assessment System, the Housing Quality Standards, the American
      Housing Survey, the Community Environmental Health Resource Center protocol, and
      the National Energy Audit Tool. The comparison shows considerable variability
      across the protocols, particularly in the collection of environmental samples or
      measurements. This may be due in part to differing end uses, as well as the fact
      that the intersection of housing and health issues is not clearly in the domain
      of either profession. Housing professionals typically focus on durability and
      affordability, while environmental health professionals are frequently focused on
      specific disease or injury vectors, not on place-based interventions. Validation
      studies at both the national and the international level are needed to determine
      how well both the hazard assessment and the resulting interventions predict
      health outcome. Standardizing and validating such protocols can help move beyond
      the existing limited categorical approaches and will help improve both
      substandard housing quality and public health.

PMID- 16448644
TI  - Well water radioactivity and risk of cancers of the urinary organs.
AB  - Water from bedrock frequently contains higher concentrations of natural
      radionuclides than water from other sources. Bladder and kidneys receive a
      radiation dose when radioactive isotopes are excreted into urine. The subjects
      for this case-cohort study were selected from all drilled wells users in Finland.
      The study comprised 61 bladder cancer and 51 kidney cancer cases diagnosed
      between 1981 and 1995, as well as a random sample of 274 reference persons,
      stratified by age and sex. The median activity concentrations of radon in drilled
      wells used by bladder and kidney cancer cases and the reference cohort were 170,
      140, and 130 Bq/L, respectively. The radium concentration was 0.01 Bq/L for all
      groups and the uranium concentrations were 0.08, 0.07, and 0.06 Bq/L,
      respectively. The bladder cancer risks associated with radon, radium, and uranium
      activity concentrations in drinking water were 1.02 (0.68-1.54) per log(100 Bq of
      radon/L), 0.73 (0.21-2.50) per log(0.1 Bq of radium/L), and 0.77 (0.32-1.89) per
      log(1 Bq of uranium/L). The corresponding figures for kidney cancer were 0.81
      (0.47-1.37), 0.12 (0.01-1.10), and 0.92 (0.36-2.35), respectively. In conclusion,
      even though ingested radionuclides from drilled wells are a source of radiation
      exposure, they are not associated with a substantially increased risk of bladder
      or kidney cancers in concentrations occurring in drilled wells.

PMID- 16448645
TI  - Histamine receptors are hot in immunopharmacology.
AB  - In addition to its well-characterized effects in the acute allergic inflammatory
      responses, histamine has been demonstrated to affect chronic inflammation and
      regulate several essential events in the immune response. Histamine can
      selectively recruit the major effector cells into tissue sites and affect their
      maturation, activation, polarization, and other functions leading to chronic
      inflammation. Histamine also regulates dendritic cells, T cells and B cells, as
      well as related antibody isotype responses. In addition, acting through its
      receptor 2, histamine positively interferes with the peripheral antigen tolerance
      induced by T regulatory cells in several pathways. The diverse effects of
      histamine on immune regulation appear to be due to differential expression and
      regulation of 4 types of histamine receptors and their distinct intracellular
      signals. In addition, differences in affinities of these receptors for histamine
      is highly decisive for the biological effects of histamine and drugs that target
      histamine receptors. This article highlights recent discoveries in histamine
      immunobiology and discusses their relevance in allergic inflammation.

PMID- 16448646
TI  - Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal
      cell lines.
AB  - Although clinical trials with GLP-2 receptor agonists are currently ongoing, the
      mechanisms behind GLP-2-induced intestinal epithelial growth remain to be
      understood. To approach the GLP-2 mechanism of action this study aimed to
      identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here
      we report the first identification of a cell line endogenously expressing
      functional GLP-2 receptors. The human intestinal epithelial cell line, FHC,
      expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein
      (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP
      accumulation (pEC(50)=9.7+/-0.04 (mean+/-S.E.M., n=4)). In addition, a naturally
      occurring human intestinal fibroblast cell line, 18Co, endogenously expressing
      GLP-2 receptor encoding mRNA (RT-PCR) and protein (Western blot) was identified.
      No receptor functionality (binding or G-protein signalling) could be demonstrated
      in 18Co cells. The identified gut-relevant cell lines provide tools for future
      clarification of the mechanisms underlying GLP-2-induced epithelial growth.

PMID- 16448647
TI  - Modulation of paracetamol antinociception by caffeine and by selective adenosine
      A2 receptor antagonists in mice.
AB  - This study investigated the involvement of adenosine receptors in the interaction
      between paracetamol and caffeine in mice, using the adenosine A2A receptor
      antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4
      triazolo[1,5-c]pyrimidine (SCH58261) and the adenosine A2B receptor antagonist 1
      propyl-8-p-sulfophenylxanthine (PSB1115), in the tail immersion and hot-plate
      tests. Paracetamol (10-200 mg/kg) was antinociceptive in both tests, but, in
      contrast to previous studies, caffeine (10 mg/kg) was pronociceptive in the tail
      immersion test, and reduced the effects of paracetamol in both tests. SCH58261 (3
      mg/kg) was antinociceptive in both tests and in its presence paracetamol (50
      mg/kg) had no further effect. PSB1115 (10 mg/kg) had little effect alone but
      potentiated the effect of paracetamol (50 mg/kg) in the hot-plate test and
      abolished it in the tail immersion test. These results suggest that adenosine A2B
      receptors may be involved in the action of paracetamol in a pathway-dependent
      manner, and also support the existence of pronociceptive adenosine A2A receptors.

PMID- 16448648
TI  - Effects of drug combinations on smooth muscle cell proliferation: an
      isobolographic analysis.
AB  - Although sirolimus is a potent inhibitor of vascular smooth muscle cell (VSMC)
      proliferation and is effective at preventing restenosis in the majority of
      clinical revascularization procedures employing sirolimus-eluting stents, some
      VSMC may escape the antiproliferative effects of sirolimus. The present study
      examines the effects of combining sirolimus with other known cell cycle-specific
      antiproliferative agents (cladribine, topotecan or etoposide) on cultured
      coronary artery VSMC proliferation and utilizes a novel isobolographic approach
      to determine whether sirolimus/antiproliferative agent combinations produce
      subadditive, additive or supraadditive potentiation of antiproliferative
      activity. All agents were found to inhibit coronary artery VSMC proliferation in
      a dose-dependent manner. Cladribine was found to potentiate the antiproliferative
      activity of sirolimus in either an additive or supraadditive manner, depending
      upon the cladribine concentration. Topotecan potentiated the sirolimus
      antiproliferative activity by simple additivity while etoposide yielded
      subadditive potentiation. The present results demonstrate the utility of
      isobolographic analysis for identifying and optimizing antiproliferative drug
      combinations.

PMID- 16448649
TI  - Differential epithelial expression of SHH and FOXF1 in usual and nonspecific
      interstitial pneumonia.
AB  - Morphogenetic factors have been shown to play a role in embryogenesis and post
      embryonic disease. Interstitial pulmonary fibrosis is a chronic and often
      progressive disorder that can lead to end-stage cystic lung. Its two major
      subtypes, usual interstitial pneumonitis (UIP) and nonspecific interstitial
      pneumonitis (NSIP) differ in their response to immunosuppressive regimens, with
      UIP having a significantly worse prognosis. The clinical and histologic overlap
      between these disorders is substantial, and there are no ancillary findings that
      can accurately distinguish them. We examined surgical and autopsy specimens of
      lung in 13 cases of patients with either UIP or the fibrotic variant of NSIP
      (NSIP-F) for their expression of Sonic hedgehog (Shh) and Foxf1 in situ. We
      identified a pattern of strong Shh expression with weak expression of Foxf1 in
      all cases of UIP and a complementary expression of Shh and Foxf1 in cases of NSIP
      F. We conclude that morphogenetic genes may participate differentially in the
      pathogenesis of UIP and NSIP-F.

PMID- 16448650
TI  - Role of RhoA/ROCK-dependent actin contractility in the induction of tenascin-C by
      cyclic tensile strain.
AB  - In chick embryo fibroblasts, the mRNA for extracellular matrix protein tenascin-C
      is induced 2-fold by cyclic strain (10%, 0.3 Hz, 6 h). This response is
      attenuated by inhibiting Rho-dependent kinase (ROCK). The RhoA/ROCK signaling
      pathway is primarily involved in actin dynamics. Here, we demonstrate its crucial
      importance in regulating tenascin-C expression. Cyclic strain stimulated RhoA
      activation and induced fibroblast contraction. Chemical activators of RhoA
      synergistically enhanced the effects of cyclic strain on cell contractility.
      Interestingly, tenascin-C mRNA levels perfectly matched the extent of RhoA/ROCK
      mediated actin contraction. First, RhoA activation by thrombin, lysophosphatidic
      acid, or colchicine induced tenascin-C mRNA to a similar extent as strain.
      Second, RhoA activating drugs in combination with cyclic strain caused a super
      induction (4- to 5-fold) of tenascin-C mRNA, which was again suppressed by ROCK
      inhibition. Third, disruption of the actin cytoskeleton with latrunculin A
      abolished induction of tenascin-C mRNA by chemical RhoA activators in combination
      with cyclic strain. Lastly, we found that myosin II activity is required for
      tenascin-C induction by cyclic strain. We conclude that RhoA/ROCK-controlled
      actin contractility has a mechanosensory function in fibroblasts that correlates
      directly with tenascin-C gene expression. Previous RhoA/ROCK activation, either
      by chemical or mechanical signals, might render fibroblasts more sensitive to
      external tensile stress, e.g., during wound healing.

PMID- 16448651
TI  - Activation of Rho after traumatic brain injury and seizure in rats.
AB  - Traumatic brain injury (TBI) is characterized by a progressive cell loss and a
      lack of axonal regeneration. In the central nervous system (CNS), the Rho
      signaling pathway regulates the neuronal response to growth inhibitory proteins
      and regeneration of damaged axons, and Rho activation is also correlated with an
      increased susceptibility to apoptosis. To evaluate whether traumatic brain injury
      (TBI) results in changes in Rho activation in vulnerable regions of the brain,
      GTP-RhoA pull down assays were performed on rat cortical and hippocampal tissue
      homogenates obtained from 24 h to 3 days following lateral fluid percussion brain
      injury (FPI). Following FPI, a significantly increased RhoA activation was
      observed from 24 h to 3 days post-injury in the cortex and by 3 days in the
      hippocampus ipsilateral to the injury. We also detected activated RhoA in the
      cortex and hippocampus contralateral to the injury, without concomitant changes
      in total RhoA levels. To determine if immediate post-traumatic events such as
      seizures may activate Rho, we examined RhoA activation in the brains of rats with
      kainic acid-induced seizures. Severe seizures resulted in bilateral RhoA
      activation in the cortex and hippocampus. Together, these results indicate that
      RhoA is activated in vulnerable brain regions following traumatic and epileptic
      insults to the CNS.

PMID- 16448652
TI  - Traumatic axonal injury in the perisomatic domain triggers ultrarapid secondary
      axotomy and Wallerian degeneration.
AB  - Traumatic axonal injury (TAI) arising from diffuse brain injury (DBI) results in
      focally impaired axonal transport with progressive swelling and delayed
      disconnection over several hours within brainstem axons. Neocortical DBI-mediated
      perisomatic axotomy does not result in neuronal death, suggesting that a
      comparably delayed axotomy progression was responsible for this unanticipated
      response. To evaluate delayed perisomatic axotomy, the current study was
      initiated. Rats received intracerebroventricular 10-kDa dextran followed by
      moderate midline/central fluid percussion injury (FPI) or FPI alone. At 15, 30,
      60, and 180 min post-injury, light and transmission electron microscopy
      identified impaired axonal transport via antibodies targeting amyloid precursor
      protein (APP), while double-label fluorescent microscopy explored concomitant
      focal axolemmal alterations via dextran-APP co-localization. At 15 min post
      injury, perisomatic TAI was identified with LM within dorsolateral and ventral
      posterior thalamic nuclei. Using TEM, many sustaining somata and related
      proximal/distal axonal segments revealed normal ultrastructural detail that was
      continuous with focal axonal swellings characterized by cytoskeletal and
      organelle pathology. In other cases, axotomy was confirmed by loss of axonal
      continuity distal to the swelling. By 30 min post-injury, perisomatic axotomy
      predominated. By 60-180 min, somatic, proximal axonal segment, and swelling
      ultrastructure were comparable to earlier time points although swelling diameter
      increased. Distal axonal segment ultrastructure now revealed the initial stages
      of Wallerian degeneration. The site of perisomatic axotomy did not internalize
      dextran, suggesting that its pathogenesis occurred independent of altered
      axolemmal permeability. Collectively, this DBI-mediated ultrarapid perisomatic
      axotomy and its sequelae further illustrate the varied axonal responses to
      trauma.

PMID- 16448654
TI  - Quantifying biomechanical motion using Procrustes motion analysis.
AB  - The ability to quantify and compare the movements of organisms is a central focus
      of many studies in biology, anthropology, biomechanics, and ergonomics. However,
      while the importance of functional motion analysis has long been acknowledged,
      quantitative methods for identifying differences in motion have not been widely
      developed. In this article, we present an approach to the functional analysis of
      motion and quantification of motion types. Our approach, Procrustes Motion
      Analysis (PMA) can be used to distinguish differences in cyclical, repeated, or
      goal-directed motions. PMA exploits the fact that any motion can be represented
      by an ordered sequence of postures exhibited throughout the course of a motion.
      Changes in posture from time step to time step form a trajectory through a
      multivariate data space, representing a specific motion. By evaluating the size,
      shape, and orientation of these motion trajectories, it is possible to examine
      variation in motion type within and among groups or even with respect to
      continuous variables. This represents a significant analytical advance over
      current approaches. Using simulated and digitized data representing cyclical,
      repeated and goal-directed motions, we show that PMA correctly identifies
      distinct motion tasks in these data sets.

PMID- 16448653
TI  - Enhanced urinary odor discrimination in female aromatase knockout (ArKO) mice.
AB  - We asked whether odor discrimination abilities are sexually dimorphic in mice
      and, if so, whether the perinatal actions of estradiol contribute to these sex
      differences. The ability to discriminate different types of urinary odors was
      compared in male and female wild-type (WT) subjects and in mice with a homozygous
      null mutation of the estrogen synthetic enzyme, aromatase (aromatase knockout;
      ArKO). Olfactory discrimination was assessed in WT and ArKO male and female mice
      after they were gonadectomized in adulthood and subsequently treated with
      estradiol benzoate. A liquid olfactometer was used to assess food-motivated
      olfactory discrimination capacity. All animals eventually learned to distinguish
      between urinary odors collected from gonadally intact males and estrous females;
      however, WT males as well as ArKO mice of both sexes learned this discrimination
      significantly more rapidly than WT females. Similar group differences were
      obtained when mice discriminated between urinary odors collected from gonadally
      intact vs. castrated males or between two non-social odorants, amyl and butyl
      acetate. When subjects had to discriminate volatile urinary odors from
      ovariectomized female mice treated with estradiol sequenced with progesterone
      versus estradiol alone, ArKO females quickly acquired the task whereas WT males
      and females as well as ArKO males failed to do so. These results demonstrated a
      strong sex dimorphism in olfactory discrimination ability, with WT males
      performing better than females. Furthermore, female ArKO mice showed an enhanced
      ability to discriminate very similar urinary odorants, perhaps due to an
      increased sensitivity of the main olfactory nervous system to adult estradiol
      treatment as a result of perinatal estrogen deprivation.

PMID- 16448655
TI  - Application of solid-phase extraction and liquid chromatography-mass spectrometry
      to the determination of neonicotinoid pesticide residues in fruit and vegetables.
AB  - A rapid and simple method for simultaneous analysis of four neonicotinoid
      insecticides including acetamiprid, imidacloprid, thiacloprid and thiamethoxam in
      fruit and vegetable matrices has been developed. For instance, ready-to-use
      cartridges filled with a macroporous diatomaceous material were used to extract
      in a single step insecticide residues with dichloromethane from aqueous-acetone
      extracts of fruits and vegetables. The eluate was evaporated, the residue
      redissolved with methanol and then analyzed by liquid chromatography-mass
      spectrometry in the electrospray ionization (ESI) positive mode. Average
      recoveries of the four pesticides were between 74.5 and 105% at both spiking
      levels 0.1 and 1.0 mg kg(-1) in peach, pear, courgette, celery and apricot.
      Relative standard deviations (RSDs) were less than 10% for all of the recovery
      tests. The calculated limits of quantitation (LOQs) (0.1-0.5 mg kg(-1)) were
      equal or lower then the maximum residue limits (MRLs) established by European
      legislation (0.1-0.5 mg kg(-1)). The proposed method is fast, easy to perform and
      could be utilized for monitoring of pesticides residues.

PMID- 16448656
TI  - Optimization of a reversed-phase high-performance liquid chromatography/mass
      spectrometry method for characterizing recombinant antibody heterogeneity and
      stability.
AB  - An enhanced analytical RP-HPLC/MS method was developed for monitoring the
      stability and production of intact and fragmented monoclonal antibodies (MAbs).
      The use of high column temperatures (70-80 degrees C), organic solvents with high
      eluotropic strength coefficients (isopropyl and n-propyl alcohols), and Zorbax
      StableBond columns, were critical for good recovery and resolution of
      immunoglobulin G1 (IgG1) and IgG2 monoclonal antibodies. Using this method,
      cleavage products of a degraded IgG1 antibody were clearly separated and
      identified by in-line electrospray ionization time-of-flight (ESI-TOF) mass
      spectrometry generating exact masses and unique terminal ladder sequences. The
      glycosylation profile, including mapping of the terminal galactose and fucose
      heterogeneity of the N-linked sugars, was determined by mass spectrometry of
      intact MAbs. In addition, we discovered that several IgG2 MAbs exhibited greater
      structural heterogeneity compared to IgG1s. Mass spectral characterization data
      and reduction data suggested that the heterogeneity is disulfide related. This
      reversed-phase LC/MS method represents a key advancement in monitoring intact MAb
      production and stability.

PMID- 16448657
TI  - Affinity capillary electrophoresis with a DNA-nanoparticle conjugate as a new
      tool for genotyping.
AB  - We have developed a novel method for genotyping based on free solution affinity
      capillary electrophoresis. We prepared DNA-nanoparticle conjugates by mixing
      biotin-modified DNA and NeutrAvidin-modified polystyrene nanoparticles; this
      mixture was then injected into a capillary. Subsequently, we injected the
      fluorescent-labeled sample DNAs into the capillary, applied the voltage,
      increased its temperature after 7 min, and detected the fluorescence at its
      anodic end. This novel method was applied for genotyping human c-K-ras, and the
      three genotypes were definitely distinguishable with high reproducibility. This
      method can be easily automated, and it is useful for high-throughput gene
      mutation analysis.

PMID- 16448658
TI  - Determination of levoglucosan in atmospheric aerosols using high performance
      liquid chromatography with aerosol charge detection.
AB  - A sensitive method for analysis of levoglucosan (1,6-anhydro-beta,d
      glucopyranose) and other monosaccharide anhydrides, compounds present in biomass
      combustion smoke, was investigated employing high-performance liquid
      chromatography (HPLC) with recently developed aerosol charge detection. Aerosol
      charge detection involves the conversion of the column effluent to an aerosol,
      which is charged to produce a current. Use of a cation-exchange column and a pure
      water eluent was found to separate levoglucosan and mannosan from other aerosol
      components with a detection limit of about 90 ng mL(-1) for levoglucosan or 5 ng
      injected. This method was demonstrated by successful analysis of aerosol filter
      samples from three locations.

PMID- 16448659
TI  - Characterization of stable aluminium-citrate species as reference substances for
      aluminium speciation by ion chromatography.
AB  - Well-defined anionic aluminium-citrate species are accessible from crystalline
      aluminium complexes. The solution chemistry of those species can be investigated
      using ion chromatography as a powerful tool for aluminium speciation in aqueous
      samples. The separation of three anionic aluminium-citrate complexes by anion
      exchange chromatography is possible within 5 min using isocratic conditions. The
      element specific detection was done by online coupled ICP-AES. The remaining
      charge of the complexes after dissolution can be determined by ion chromatography
      using a retention model. Time-dependent monitoring of the species distribution
      gave information about the species stabilities and the decomposition pathways.
      With citric acid as an aluminium chelator partially very stable anionic species
      are observed. These complexes are important components in biological systems. An
      example for the practical use of the separation method and the well-defined
      standards is given for plant sap, which showed two species with similar behavior
      compared to the investigated stable aluminium-citrate complexes.

PMID- 16448660
TI  - Rapid quantification and characterization of soyasaponins by high-performance
      liquid chromatography coupled with electrospray mass spectrometry.
AB  - A method using high-performance liquid chromatography (HPLC) with electrospray
      ionization mass spectrometry (ESI-MS) in the negative mode is presented for the
      quantification and characterization of different soyasaponins using six authentic
      soyasaponin standards. This method was successfully applied to the rapid
      separation of diverse soyasaponins, more than 50, including soyasaponins A in
      different degrees of acetylation, and soyasaponins B in both their 2,3-dihydro
      2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP)-conjugated and non-conjugated forms
      in different samples in one single run for only 30 min. Standard calibration
      curve was linear over the concentration range of 0.010-1.0 mg/L for each
      soyasaponin. Within-day and day-to-day relative standard deviations were less
      than 9.2 and 13.1%, respectively.

PMID- 16448661
TI  - Fe3O4 and gamma-Fe2O3 nanoparticles for the adsorption of Co2+ from aqueous
      solution.
AB  - The adsorption of Co2+ ions from nitrate solutions using iron oxide nanoparticles
      of magnetite (Fe3O4) and maghemite (gamma-Fe2O3) has been studied. The adsorption
      of Co2+ ions on the surface of the particles was investigated under different
      conditions of oxide content, contact time, solution pH, and initial Co2+ ion
      concentration. It has been found that the equilibrium can be attained in less
      than 5 min. The maximum loading capacity of Fe3O4 and gamma-Fe2O3 nanoparticles
      is 5.8 x 10(-5) and 3.7 x 10(-5) mol m(-2), respectively, which are much higher
      than the previously studied, iron oxides and conventional ion exchange resins.
      Co2+ ions were also recovered by dilute nitric acid from the loaded gamma-Fe2O3
      and Fe3O4 with an efficiency of 86 and 30%, respectively. That has been explained
      by the different mechanisms by including both the surface and structural loadings
      of Co2+ ions. The surface adsorption of Co2+ on Fe3O4 and gamma-Fe2O3
      nanoparticles has been found to have the same mechanism of ion exchange reaction
      between Co2+ in the solution and proton bonded on the particle surface. The
      conditional equilibrium constants of surface adsorption of Co2+ on Fe3O4 and
      gamma-Fe2O3 nanoparticles have been determined to be log K=-3.3+/-0.3 and -3.1+/
      0.2, respectively. The structural loading of Co2+ ions into Fe3O4 lattice has
      been found to be the ion exchange reaction between Co2+ and Fe2+ while that into
      gamma-Fe2O3 lattice to fill its vacancy. The effect of temperature on the
      adsorption of Co2+ was also investigated, and the value of enthalpy change was
      determined to be 19 kJ mol(-1).

PMID- 16448662
TI  - Interaction forces between poly(amidoamine) (PAMAM) dendrimers adsorbed on gold
      surfaces.
AB  - Interaction forces between two gold surfaces with adsorbed poly(amidoamine)
      (PAMAM) dendrimers (generations G3.0 and G5.0) have been investigated using
      colloidal probe atomic force microscopy (AFM). In the absence of dendrimers or at
      their low concentrations, an attractive force derived from the van der Waals
      interaction was observed. On the other hand, this attractive interaction changed
      to repulsion with increasing dendrimer concentration. The origin of the repulsion
      can be attributed to either an electric double layer interaction or a steric
      effect of the adsorbed dendrimers, depending on the concentration of dendrimer.
      The steric hindrance was also influenced by the generation of the dendrimer; the
      force-detectable distance in the presence of PAMAM G5.0 dendrimer was slightly
      longer than that in the presence of G3.0 dendrimer. In order to estimate the
      occupied area of each dendrimer adsorbed on gold, quartz crystal microbalance
      (QCM) measurement was also carried out.

PMID- 16448663
TI  - Temperature and concentration effects on electrolyte transport across porous thin
      film composite nanofiltration membranes: Pore transport mechanisms and energetics
      of permeation.
AB  - The influence of temperature and concentration on nanofilter charge density and
      electrolyte pore transport mechanisms is reported. Crossflow filtration
      experiments were performed to measure transport of several electrolytes (NaCl,
      NaNO3, NaClO4, CaCl2, MgCl2, and MgSO4) across two commercially available thin
      film composite nanofiltration membranes in the range 5-41 degrees C. Experiments
      were also performed with selected salts in the range 1-50 meq/L to quantify
      concentration effects. Three different approaches, irreversible thermodynamics,
      extended Nernst-Planck formulation, and theory of rate processes, were employed
      to interpret retentions of these symmetric and asymmetric electrolytes at varying
      temperature and concentration. Increasing feed water temperature slightly
      increased electrolyte reflection coefficients and only weakly increased
      permeability compared with neutral solutes. Electromigration and convection
      tended to counteract each other at high fluxes explaining the weak temperature
      dependence of the reflection coefficient. Changes in membrane surface charge
      density with temperature were attributed to increased adsorption of electrolytes
      on the polymer constituting the active layer. Activation energy of permeation for
      charged solutes was primarily determined by the Donnan potential at the membrane
      feed water interface. Electrolyte permeation was shown to be an enthalpy-driven
      process that resulted in small entropy changes. Increasing sorption capacity with
      temperature and low sorption energies indicated that co-ion sorption on polymeric
      membranes was an endothermic physicosorption process, which appears to determine
      temperature dependence of electrolyte permeation at increased feed
      concentrations.

PMID- 16448665
TI  - A novel chemistry for conjugating pneumococcal polysaccharides to Luminex
      microspheres.
AB  - Here we describe a novel method to conjugate pneumococcal polysaccharides (PnPS)
      to Luminex microspheres for use in serological assays. 4-(4,6
      dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium (DMTMM) modification of PnPS
      and conjugation to carboxyl functional groups on Luminex microspheres (COOH-DMTMM
      method) was shown to be a reproducible chemistry that efficiently conjugated PnPS
      to Luminex microspheres without affecting the antigenicity of a broad set of
      PnPS. The COOH-DMTMM method was compared to three other methods for robustness,
      reproducibility and effect on PnPS antigenicity in a multiplexed assay format.
      The other methods examined included adsorption of the unmodified PnPS to Luminex
      microspheres, oxidation of the PnPS to conjugate them to amino-modified
      microspheres using carbodiimide chemistry and poly-l-lysine modification of the
      PnPS before conjugating to carboxy Luminex microspheres using carbodiimide
      chemistry. Of the four methods, the COOH-DMTMM chemistry was shown to be a robust
      methodology, producing stable PnPS coupled microspheres with a 4-log dynamic
      range and low cross-reactivity when used in a PnPS-specific IgG serology assay.
      This novel chemistry should be useful for developing serological assays to
      measure antibodies to polysaccharides for use in vaccine and epidemiology
      studies.

PMID- 16448664
TI  - Analysis of neutralizing antibodies to therapeutic interferon-beta in multiple
      sclerosis patients: a comparison of three methods in a large Australasian cohort.
AB  - Persistent high-titre neutralizing antibodies (NAB) to therapeutic interferon
      beta(IFNbeta)in multiple sclerosis patients reduce therapeutic efficacy.
      Difficulties in standardization of cell-based bioactivity assays have hindered
      interlaboratory comparison of NAB titres and the determination of a clinically
      relevant definition of seropositivity. We determined NAB status in Australasian
      multiple sclerosis patients receiving IFNbetausing both the antiviral cytopathic
      effect (CPE) assay (n = 227) and the more specific ELISA for the type I
      interferon-inducible MxA protein (n = 350). While the log(10) titres determined
      in the two assays were highly correlated (p < 0.0001; r = 0.967) with similar
      distributions, the MxA assay was more sensitive, detecting lower concentrations
      of NAB than the CPE assay. The range of titres determined in the CPE assay was 10
      to >7290; and 9 to 53,700 in the MxA assay, with ranked titre distribution
      highlighting the arbitrary nature of currently accepted definitions of NAB
      seropositivity. Bioactivity of injected IFNbetawas significantly reduced in NAB
      positive patients (p = 0.006; NAB MxA titres = 184 to 5340) compared to NAB
      negative patients as assessed ex vivo using real-time RT-PCR analysis of MxA gene
      induction. The range of MxA mRNA levels in healthy controls was remarkably
      consistent with previously published results, regardless of the assay
      standardization method [Gilli, F., Sala, A., Marnetto, F., Lindberg, R.L.,
      Leppert, D. and Bertolotto, A. (2003) Comparison of IFNbeta bioavailability
      evaluations by MxA mRNA using two independent quantification methods. Abstract,
      ECTRIMS Meeting, Milan, Italy; Pachner, A., Narayan, K., Price, N., Hurd, M. and
      Dail, D. (2003a) MxA Gene Expression Analysis as an Interferon-beta Bioactivity
      Measurement in Patients with Multiple Sclerosis and the Identification of
      Antibody-Mediated Decreased Bioactivity. Mol. Diagn. 7, 17-25]. Assessment of
      IFNbetaresponse ex vivo accounts for both circulating factors and the cellular
      response to IFNbeta, and the data support the development of the MxA gene
      induction assay for the routine screening of patients receiving IFNbeta.

PMID- 16448666
TI  - Isolation of cell specific peptide ligands using fluorescent bacterial display
      libraries.
AB  - Methods for identifying and producing cell specific affinity reagents are
      critical in cell detection, separation, and therapeutic delivery applications,
      yet remain difficult and time consuming. To address these limitations, a rapid
      and quantitative screening approach was developed using intrinsically fluorescent
      bacterial display peptide libraries and fluorescence-activated cell sorting
      (FACS). High-throughput screening of fluorescent libraries yielded a panel of
      peptide ligands mediating specific recognition of human breast cancer tumor
      cells. Clonal populations of fluorescent, peptide-displaying bacteria enabled
      single-step, fluorescent labeling of the target cells for cytometry and
      microscopy analysis. Isolated peptides could be categorized into several distinct
      groups possessing strong consensus sequences with as many as six identities.
      Importantly, individual clones exhibited high specificity target cell binding,
      with more than 80-fold increased binding to tumor cells (ZR-75-1) relative to
      cell lines derived from healthy tissue (HMEC, MCF-10A). Fluorescent display
      libraries thus provide a powerful new methodology for parallel identification of
      cell specific affinity ligands.

PMID- 16448667
TI  - Temporal association of entomopathogenic nematodes (Rhabditida: Steinernematidae
      and Heterorhabditidae) and bacteria.
AB  - Galleria mellonella L. larvae were infected with three species (seven strains) of
      Steinernema spp. or three species (three strains) of Heterorhabditis spp.
      Infected larvae were incubated at 22, 27, and 32 degrees C. Larvae were dorsally
      dissected every 6h over a 48-h period. Hemolymph was collected and streaked on
      tryptic soy agar plates. Several non-symbiotic bacterial species were identified
      from infected insect cadavers: Enterobacter gergoviae, Vibrio spp., Pseudomonas
      fluorescens type C, Serratia marcescens, Citrobacter freundii, and Serratia
      proteomaculans. At 18-24 h incubation, the nematode-associated symbiont occurred
      almost exclusively. Bacterial associates generally appeared outside the 18-24 h
      window. Infective juveniles of Steinernema feltiae (Filipjev) (27), Steinernema
      riobrave Cabanillas, Poinar, and Raulston (Oscar), or Steinernema carpocapsae
      (Weiser) (Kapow) were left untreated, or surface sterilized using thimerosal,
      then pipetted under sterile conditions onto tryptic soy agar plates. Several
      additional species of associated bacteria were identified using this method
      compared with the less extensive range of species isolated from infected G.
      mellonella. There was no difference in bacterial species identified from non
      sterile or surface sterilized nematodes, suggesting that the bacteria identified
      originated from either inside the nematode or between second and third stage
      juvenile cuticles. Infective juveniles of S. feltiae (Cowles), S. carpocapsae
      (Cowles), and H. bacteriophora Poinar (Cowles) were isolated from field samples.
      Nematodes were surface-sterilized using sodium hypochlorite, mixed with G.
      mellonella hemolymph, and pipetted onto Biolog BUG (with blood) agar. Only the
      relevant symbionts were isolated from the limited number of samples available.
      The nematodes were then cultured in the laboratory for 14 months (sub-cultured in
      G. mellonella 7-times). Other Enterobacteriaceae could then be isolated from the
      steinernematid nematodes including S. marcescens, Salmonella sp., and E.
      gergoviae, indicating the ability of the nematodes to associate with other
      bacteria in laboratory culture.

PMID- 16448668
TI  - Idiopathic neuropathy, prediabetes and the metabolic syndrome.
AB  - Peripheral neuropathy is a common problem encountered by neurologists and primary
      care physicians. While there are many causes for peripheral neuropathy, none can
      be identified in a large percentage of patients ("idiopathic neuropathy").
      Despite its high prevalence, idiopathic neuropathy is poorly studied and
      understood. There is evolving evidence that impaired glucose tolerance
      (prediabetes) is associated with idiopathic neuropathy. Preliminary data from a
      multicenter study of diet and exercise in prediabetes (the Impaired Glucose
      Tolerance Neuropathy Study) suggests a diet and exercise counseling regimen based
      on the Diabetes Prevention Program results in improved metabolic measures and
      small fiber function. Prediabetes is part of the Metabolic Syndrome, which also
      includes hypertension, hyperlipidemia and obesity. Individual aspects of the
      Metabolic Syndrome influence risk and progression of diabetic neuropathy and may
      play a causative role in neuropathy both for those with prediabetes, and those
      with otherwise idiopathic neuropathy. Thus, a multifactorial treatment approach
      to individual components of Metabolic Syndrome may slow prediabetic neuropathy
      progression or result in improvement.

PMID- 16448669
TI  - Morphological features of nerves in skin biopsies.
AB  - Skin biopsy is an effective test for diagnosis of peripheral nerve disorders. The
      most commonly reported indication of abnormality in a skin biopsy is reduction of
      epidermal nerve density. Morphological changes of epidermal nerves and the
      underlying subepidermal nerve plexus provide added evidence for the presence of
      neuropathy. We determined the prevalence of epidermal axon swellings, dermal axon
      swellings, and a unique type of epidermal nerve that we call a crawler, in a
      group of normal subjects, diabetic subjects, and patients with idiopathic small
      fiber neuropathy. Other morphologic features examined include thinning of the
      subepidermal nerve plexus, sprouts at nerve terminals, encapsulated endings, and
      immunoreactive basal cells.

PMID- 16448670
TI  - The ratio of P40 monomer to dimer is an important determinant of IL-12
      bioactivity.
AB  - IL-12 is a 75 kDa heterodimer (IL12p70) comprised of independently regulated
      disulfide-linked 40 kDa (p40) and 35 kDa (p35) subunits. The p40 subunit exists
      extracellularly as a monomer (IL12p40) or dimer (IL12(p40)2) and can antagonize
      the action of IL12p70. Given the disagreement in the literature over the
      physiologic roles for IL12p70, IL12p40, and IL12(p40)2, we asked whether the
      bioactivity of IL-12 depended only on the concentration of the IL12p70 subunit
      alone or whether the relative concentrations of IL12p70, IL12p40, and IL12(p40)2
      and their competitive binding with the IL-12 receptor are essential for
      determining IL-12 bioactivity under simulated human physiologic conditions. A
      mathematical model for IL-12 bioactivity was created by incorporating the
      production of IL12p70, IL12p40, and IL12(p40)2 by mature human DC and the
      interaction of these species with the IL-12 receptor. Using this model, we
      explored the effects of IFN-gamma, IL-4, and PGE2 concentrations on the
      bioactivity of IL-12. The simulations suggest that the concentration of IL12p70
      alone is not indicative of IL-12 bioactivity; rather, the bioactivity of IL-12
      produced by mature DC depends on IL12p70, IL12p40, and IL12(p40)2 production and
      their competitive interaction with the IL-12 receptor. In addition to the
      typically measured quantities of total p40 (IL12p40 + IL12(p40)2) and IL12p70,
      the ratio of IL12p40 to IL12(p40)2 is an equally important, yet underreported,
      determinant of IL-12 bioactivity.

PMID- 16448671
TI  - Nutraceuticals, herbals and related products.

PMID- 16448672
TI  - Mathematical analysis of a metapopulation model with space-limited recruitment.
AB  - We investigate a mathematical aspect of a multi-species' sessile metapopulation
      model with space-limited recruitment proposed by Iwasa et al. in 1986. We define
      some basic reproduction numbers to show the threshold condition for the stability
      of trivial steady state and the existence of coexistent steady state. We show the
      existence of steady state where all species exist when some reproduction numbers
      are greater than one by the fixed point theorem. And we construct the Lyapunov
      function to show the global stability of trivial steady state when some basic
      reproduction numbers are not greater than one.

PMID- 16448673
TI  - Competition in chemostat-type equations with two habitats.
AB  - Competition on a model with nutrient recycling is considered. The model is based
      on a chemostat-type equation which is used to study population dynamics of
      microorganisms. The model consists of four organisms competing for a limiting
      nutrient. Nutrient is supplied both from the in-flow of medium and a recycling
      with delay, the latter is generated from dead organisms by bacterial
      decomposition. This paper shows that the model undergoes a Hopf bifurcation
      through a critical value of time delay when the in-flow is small. Coexistence of
      four organisms competing for one limiting nutrient is indicated by numerical
      simulation results.

PMID- 16448674
TI  - Permanence of delayed population model with dispersal loss.
AB  - Permanence of a dispersal single-species population model where environment is
      partitioned into several patches is considered. The species not only requires
      some time to disperse between the patches but also has some possibility to die
      during its dispersion. The model is described by delay differential equations.
      The existence of 'super' food-rich patch is proved to be sufficient to ensure
      partial permanence of the model. It is also shown that partial permanence implies
      permanence if each food-poor patch is chained to the super food-rich patch.
      Furthermore, it is proven that partial persistence is ensured if there exist food
      rich patches and the dispersion of the species among the patches are small. When
      the dispersion is large, the partial persistence is realized under relatively
      small dispersion time.

PMID- 16448676
TI  - Increased ethanol consumption and preference and decreased ethanol sensitivity in
      female FAAH knockout mice.
AB  - Previous studies have shown that mice lacking cannabinoid (CB1) receptor gene
      consume markedly reduced levels of ethanol. Mice lacking the enzyme fatty acid
      amidohydrolase (FAAH) are severely impaired in their ability to degrade
      anandamide (AEA) and therefore represent a unique animal model in which to
      examine the function of AEA in vivo on ethanol-drinking behavior. In the current
      study, FAAH(-/-) mice were tested for ethanol, saccharin or quinine consumption
      and preference. Ethanol-induced hypothermia, and sleep time were used to evaluate
      the sensitivity to acute effects of ethanol. Ethanol intake and preference were
      increased only in female FAAH(-/-) mice. No significant difference in saccharin
      or quinine consumption or preference was observed between genotypes. Female FAAH(
      /-) mice were less sensitive to the hypothermic and sedative/hypnotic effects of
      acute ethanol. Supersensitivity to exogenous AEA was noted in both male and
      female FAAH(-/-) mice. Following voluntary ethanol consumption, CB1 receptor
      levels and function were down-regulated in male FAAH(+/+), FAAH(-/-), and female
      FAAH(+/+) mice but not in female FAAH(-/-) mice. Our results suggest that absence
      of an effect in male mice indicates a sex-linked mechanism that is secondary (or
      modulatory) to FAAH function. Thus, the data suggest that FAAH may be indirectly
      related to ethanol intake and sensitivity and central endocannabinoidergic
      mediated pathways may regulate ethanol consumption.

PMID- 16448675
TI  - Polymorphisms in insulin-related genes predispose to specific KRAS2 and TP53
      mutations in colon cancer.
AB  - Risk factors for colon cancer may not only influence the overall risk of cancer
      but also the risk for specific types of mutations. We evaluated the effect of
      polymorphisms in four insulin-related genes (G972R in IRS1, G1057D in IRS2, a CA
      repeat in IGFI and an A/C polymorphism at -202 of IGFBP3) on the risk of
      microsatellite instability and KRAS2 and TP53 mutations in a population-based set
      of 1788 cases of colon cancer and 1981 controls. The GR/RR IRS1 genotypes were
      associated with an increased risk of colon cancers with the KRAS2 G12D mutation
      (OR 2.3, 95% CI 1.5, 3.5 versus controls, OR 1.7, 95% CI 1.1, 2.6 versus KRAS2
      wild type), the "no 192" IGFI genotype increased the risk of the KRAS2 G13D
      mutation (OR 2.3, 95% CI 1.2, 4.2 versus controls, OR 2.1, 95% CI 1.1, 4.0 versus
      wild type), and the DD IRS2 genotype increased the risk of the G12V KRAS2
      mutation (OR 1.8, 95% CI 0.9, 3.5 versus controls, OR 2.0, 95% CI 1.0, 4.0 versus
      wild type). Polymorphisms in IRS1 and IGF1 were also associated with an
      approximately two-fold increased risk of specific TP53 mutations relative to
      controls without cancer. We conclude that polymorphisms in some insulin-related
      genes are associated with an increased risk of colon cancer with specific KRAS2
      and TP53 mutations, implying a link between these genetic changes and specific
      mutational pathways in carcinogenesis.

PMID- 16448677
TI  - Tolerance and withdrawal in goldfish exposed to ethanol.
AB  - Acute ethanol exposure decreases regulated body temperature. Tolerance and
      dependence develop with continued exposure. Removal of ethanol following chronic
      exposure produces withdrawal. There is little information on the time course for
      the development of tolerance and disagreement about the presence of a rebound
      effect on body temperature during withdrawal. For tolerance, we monitored the
      selected temperature [T(sel)] of goldfish [Carassius auratus] for 8 h while they
      were exposed to one of three doses of ethanol. During the period from 90 to 150
      min post-exposure, T(sel) was: control: 24.1+/-0.07 degrees C; 0.4% ethanol:
      21.9+/-0.09 degrees C; 0.8% ethanol: 21.3+/-0.05 degrees C; 1.1% ethanol: 18.4+/
      0.10 degrees C. The difference between control and experimental T(sel) decreased
      by the following amounts for the final 1.5 h in the gradient: 0.4% ethanol:
      2.60+/-0.12 degrees C; 0.8% ethanol: 1.58+/-0.09 degrees C; 1.1% ethanol: 4.08+/
      0.12 degrees C. At all 3 doses, tolerance proceeded in a stepwise manner rather
      than continuously. Temperature regulation during withdrawal was evaluated by
      maintaining the goldfish in 0.8% ethanol for three days and subsequently
      monitoring T(sel) in an ethanol-free temperature gradient for 36 h. During
      withdrawal there was no evidence for an effect on T(sel); experimental and
      control values were nearly identical.

PMID- 16448678
TI  - Detection of free fatty acids following a conditioned taste aversion in rats.
AB  - A gustatory transduction mechanism for free fatty acids (FFAs) has been described
      in isolated rat taste receptor cells; however, the ability of behaving rats to
      detect FFAs has not been characterized. Through conditioned taste aversion (CTA)
      methodology, this study defines the ability of rats to detect and avoid the two
      principal FFA components of corn oil, linoleic and oleic acid. Following taste
      aversion conditioning, rats avoided both linoleic and oleic acid at greater than
      or equal to 66 muM and failed to avoid either 44 muM linoleic or oleic acid. Rats
      demonstrated generalized avoidances between 88 muM linoleic and oleic acid
      irrespective of presenting the FFAs as either unesterified acids dissolved in 5
      mM ethanol or aqueous sodium salts, sodium linoleate and sodium oleate. Following
      a CTA to linoleic acid, rats did not show generalized avoidance of NaCl or
      ethanol, two potentially concomitant tastants in the oral cavity. A CTA to
      linoleic or oleic acid did produce a generalized avoidance to the other FFA.
      These results support the ability of rats to detect linoleic and oleic acid (>44
      muM) and suggest that the two FFAs share common orosensory properties.
      Furthermore, it is unlikely that the detection of the FFAs is due to an
      enhancement of other concomitant tastants such as saliva or the delivery
      solution.

PMID- 16448679
TI  - Novel non-enzymatic toxic peptide of Daboia russelii (Eastern region) venom
      renders commercial polyvalent antivenom ineffective.
AB  - The snake venoms are typically complex mixtures of enzymes and non-enzymatic
      peptides. Regional variation in the non-enzymatic fraction of Russell's viper
      venom from three regions of India studied. The eastern, western and southern
      regional venom upon gel permeation chromatography on sephadex-G-75 column
      resolved into three peaks. All the three overlapping peaks differ in their
      lethality and enzymatic potency. Peak III of all the regional venom found to be
      non-enzymatic, Western and southern regional venom has trypsin inhibitory
      activity with varying potencies. Interestingly, the peak III of eastern region is
      devoid of trypsin inhibitory activity. But it is highly lethal with a LD50 0.7
      mg/kg body weight and also it exhibited post-synaptic neurotoxicity. On the other
      hand southern and western regional venom's non-enzymatic peak is non-lethal and
      did not induce neurotoxic symptoms in experimental model. The antibodies
      developed against the eastern regional venom cross-reacted with the peaks I and
      II of other regional venom, but failed to cross-react with the peak III of
      western and southern regional Russell's viper venom. Commercial anti-venom
      prepared to neutralize the toxic effects of common poisonous snakes of India,
      showed positive cross-reaction against peaks I, II and III of all three regional
      venom tested, except peak III of eastern regional venom. Commercial anti-venom
      neutralized the lethal toxicity of both western and southern regional Russell's
      viper venom, and failed to neutralize the lethal effects of eastern regional
      Russell's viper venom.

PMID- 16448680
TI  - Quantitative comparison of the HSV-1 and HSV-2 transcriptomes using DNA
      microarray analysis.
AB  - The genomes of human herpes virus type-1 and type-2 share a high degree of
      sequence identity; yet, they exhibit important differences in pathology in their
      natural human host as well as in animal host and cell cultures. Here, we report
      the comparative analysis of the time and relative abundance profiles of the
      transcription of each virus type (their transcriptomes) using parallel infections
      and microarray analysis using HSV-1 probes which hybridize with high efficiency
      to orthologous HSV-2 transcripts. We have confirmed that orthologous transcripts
      belong to the same kinetic class; however, the temporal pattern of accumulation
      of 4 transcripts (U(L)4, U(L)29, U(L)30, and U(L)31) differs in infections
      between the two virus types. Interestingly, the protein products of these
      transcripts are all involved in nuclear organization and viral DNA localization.
      We discuss the relevance of these findings and whether they may have potential
      roles in the pathological differences of HSV-1 and HSV-2.

PMID- 16448681
TI  - Partial reconstitution of virus-specific memory CD8+ T cells following whole body
      gamma-irradiation.
AB  - CD8+ memory T cells are critical in providing immunity to viral infection.
      Previous studies documented that antigen-specific CD8+ memory T cells are more
      resistant to radiation-induced apoptosis than naive T cells. Here, we determined
      the number and in vivo function of memory CD8+ T cells as immune reconstitution
      progressed following irradiation. Immediately following irradiation, the number
      of memory CD8+ T cells declined 80%. As reconstitution progressed, the number of
      memory cells reached a zenith at 33% of pre-irradiation levels, and was
      maintained for 120 days post-irradiation. In vitro, memory CD8+ T cells were able
      to produce cytokines at all times post-irradiation, but when adoptively
      transferred, they were not able to expand upon rechallenge immediately following
      irradiation, but regained this ability as reconstitution progressed. When
      proliferation was examined in vitro, irradiated memory CD8+ T cells were able to
      respond to mitogenic growth but were unable to divide.

PMID- 16448682
TI  - Protein kinase CK2 phosphorylates the Nef protein from a neurovirulent simian
      immunodeficiency virus.
AB  - The Nef protein of Human Immunodeficiency Virus (HIV) and Simian Immunodeficiency
      Virus (SIV) is a pluripotent accessory protein that plays a critical role in
      disease progression. One analogous characteristic of Nef proteins from SIV and
      HIV is the ability to associate with cellular kinases. We have previously
      reported that the Nef protein from a macrophage-tropic neurovirulent SIV clone,
      SIV/17E-Fr, is associated with an unknown kinase activity that is distinct from
      the p21-associated kinase that interacts with SIVmac239 Nef. Using site-directed
      mutagenesis and kinase-specific inhibitors, we have identified this kinase as the
      ubiquitous serine/threonine kinase, protein kinase CK2.

PMID- 16448683
TI  - Effect of initial solution pH on the degradation of Orange II using clay-based Fe
      nanocomposites as heterogeneous photo-Fenton catalyst.
AB  - Effect of initial solution pH on the discoloration and mineralization of 0.2 mM
      Orange II by using two clay-based Fe nanocomposites (Fe-B (Fe supported on
      bentonite clay) and Fe-Lap-RD (Fe supported on laponite clay)) as catalysts was
      studied in detail. It was found that the initial solution pH not only influences
      the photo-catalytic activity of Fe-B and Fe-Lap-RD but also the Fe leaching from
      the two catalysts. Both catalysts show the best photo-catalytic activity at an
      initial solution pH of 3.0, and the activity of the catalysts decreases as the
      initial solution pH increases. At optimal conditions, 100% discoloration and
      mineralization of 0.2 mM Orange II are achieved in 60 and 120 min reaction in the
      presence of 10 mM H2O2, 1.0 g/L Fe-B, and 1 x 8 W UVC at initial solution pH of
      3.0. 100% discoloration and 90% mineralization of 0.2 mM Orange II are achieved
      when Fe-Lap-RD is used as catalyst under the same conditions. Both catalysts also
      display a reasonable good photo-catalytic activity and negligible Fe leaching at
      an initial solution pH of 6.6 that is very close to neutral pH. This
      characteristic makes it possible for the Fe-B and Fe-Lap-RD to have a long-term
      stability. It also becomes feasible for the photo-Fenton process to treat the
      original wastewater without the need to pre-adjust the solution pH.

PMID- 16448684
TI  - Heavy metal and trace element distributions in groundwater in natural slopes and
      highly urbanized spaces in Mid-Levels area, Hong Kong.
AB  - The lower slope of the Mid-Levels area, Hong Kong, is one the most heavily
      urbanized coastal areas in the world. A comprehensive groundwater heavy metal and
      trace element study was conducted in the Mid-Levels area aiming to investigate
      the impacts of urbanization on the aqueous distributions of these chemicals.
      Groundwater samples were collected in the upper natural slopes and the lower
      highly urbanized spaces in the area in different seasons, and analyzed for heavy
      metal and trace element contents. Compared to the results from natural slopes,
      groundwater samples in the developed spaces did not exhibit significant elevated
      levels in Zn, Cr, Cu, Cd, Pb and Fe, which are commonly found in stormwater. On
      the other hand, the samples were found to have elevated contents in Mn, V, Co and
      Mo, minor stormwater-related heavy metals, suggesting that stormwater drains may
      be leaking to some extent. However, the results suggested that the vadose zone
      could remove many of the heavy metals, protecting groundwater from being
      contaminated seriously. Statistical analysis suggested that a certain amount of
      Mn and Co was likely to be re-mobilized from natural soils due to the changes in
      local redox conditions, while Mn, V, Co and Mo may also be derived from steel
      corrosion as a result of prolonged submergence. Besides, the average B
      concentration in the developed spaces was about eight times higher than that in
      the natural slopes, indicating the presence of sewage. The mean Se concentration
      in the developed spaces was about 100 times higher than that in the natural
      slopes. About 40% of samples in the developed spaces contained Se level higher
      than the drinking water guideline value proposed by the World Health
      Organization. Se was found to be positively correlated with B and SO4(2-) (R =
      0.534 and 0.631, respectively), suggesting that Se may also be related to leakage
      from sewage pipes. Part of the Sr may come from leakage of flushing water and/or
      sewage as Sr was strongly correlated with Cl- (R = 0.929). According to the
      measured results, deep groundwater samples collected from piezometers (> 10 m in
      depth) in the urbanized spaces appeared to be virtually free from any
      anthropogenic contaminations. This study may shed important light on the
      identification and evaluation of leakage from service pipes in a particular area
      based on aqueous distributions of heavy metals and trace elements. Moreover, the
      above findings may be instructional for other coastal cities with a similar level
      of urban development to understand the potential threats to their groundwater
      resources.

PMID- 16448685
TI  - A comparison of the properties of polyurethane immobilised Sphagnum moss,
      seaweed, sunflower waste and maize for the biosorption of Cu, Pb, Zn and Ni in
      continuous flow packed columns.
AB  - The biosorption of Cu, Pb, Zn and Ni from a mixed solution of the metals was
      investigated in continuous flow packed columns containing polyurethane
      immobilised biomass. The characteristics and biosorption properties of Sphagnum
      moss, the brown seaweed Ascophyllum nodosum, waste biomass from the preparation
      of sunflower oil, and whole plant maize were compared. All the biomass types
      showed a preference for the sequestration of Pb followed by Cu, with Ni and Zn
      having roughly equal affinity. With continuous metal loading to the column there
      was an initial binding of all metals and then a displacement of the lower
      affinity metals by those with a high affinity. This led to a chromatographic
      effect in the column with breakthrough concentrations for low-affinity metals
      higher than the concentration in the feed. A similar phenomenon was found on
      desorption using acidic solutions where low-affinity metals were desorbed
      preferentially. The results also indicated that despite competitive displacement
      of one metal species by another the biomass appeared to succeed in retaining some
      low-affinity metal species indicating that there may be selective sites present
      with different affinity characteristics. When using a multi-metal solution with
      Cu, Pb, Zn and Ni at equal 10 mgl(-1) concentrations as column influent, the
      total quantities of metal sequestered were: seaweed, 117.3 mg g(-1); sunflower
      waste, 33.2 mg g(-1); Sphagnum moss, 32.5 mg g(-1); and maize, 2.3 mg g(-1). The
      use of an acid base potentiometric titration showed a relationship between the
      number of acid functional groups and biosorption capacity, although this was not
      proportional for the biomass types studied. It can, however, be used in
      conjunction with a simple classification of metals into high and low-affinity
      bands to make a preliminary assessment of a biosorption system.

PMID- 16448686
TI  - Projection of hazardous air pollutant emissions to future years.
AB  - Projecting a hazardous air pollutant (HAP) emission inventory to future years can
      provide valuable information for air quality management activities such as
      prediction of program successes and helping to assess future priorities. We have
      projected the 1999 National Emission Inventory for HAPs to numerous future years
      up to 2020 using the following tools and data: the Emissions Modeling System for
      Hazardous Air Pollutants (EMS-HAP), the National Mobile Inventory Model (NMIM),
      emission reduction information resulting from national standards and economic
      growth data. This paper discusses these projection tools, the underlying data,
      limitations and the results. The results presented include total HAP emissions
      (sum of pollutants) and toxicity-weighted HAP emissions for cancer and
      respiratory noncancer effects. Weighting emissions by toxicity does not consider
      fate, transport, or location and behavior of receptor populations and can only be
      used to estimate relative risks of direct emissions. We show these projections,
      along with historical emission trends. The data show that stationary source
      programs under Section 112 of the Clean Air Act Amendments of 1990 and mobile
      source programs which reduce hydrocarbon and particulate matter emissions, as
      well as toxic emission performance standards for reformulated gasoline, have
      contributed to and are expected to continue to contribute to large declines in
      air toxics emissions, in spite of economic and population growth. We have also
      analyzed the particular HAPs that dominate the source sectors to better
      understand the historical and future year trends and the differences across
      sectors.

PMID- 16448687
TI  - Hemostatic effect of activated factor VII without promotion of thrombus growth in
      melagatran-anticoagulated primates.
AB  - INTRODUCTION: Pharmacological enhancement of coagulation using activated
      prothrombin complex concentrate (APCC) or activated factor VII (FVIIa) might be
      useful hemostatic approaches to bleeding emergencies during anticoagulant
      therapy. However, any such intervention should not increase thrombotic risk. We
      therefore investigated their hemostatic and prothrombotic potential during
      propagation of large arterial-type thrombin in anticoagulated baboons. MATERIALS
      AND METHODS: High dose melagatran, a competitive inhibitor of thrombin (0.6
      mg/kg/h), or inactivated FVIIa (FVIIai), a competitive inhibitor of FVIIa (2
      mg/kg) were used for anticoagulation. APCC or FVIIa were administered to
      melagatran-anticoagulated animals only. Primary hemostasis was assessed as
      template bleeding time (BT). Thrombus formation was quantified as fibrin
      deposition (FD) and platelet deposition (PLD) in synthetic vascular grafts that
      were deployed for 40 min into arteriovenous shunts. RESULTS: Melagatran (n=11)
      prolonged BT to 279% (95% CI +/-140%; P<0.019), reduced FD to 33% [+/-8%;
      P<0.001]; and PLD to 39% [+/-11%; P<0.001] of untreated controls. FVIIai (n=3)
      prolonged BT (222% [+/-51%; P<0.010]) without inhibiting thrombus propagation.
      APCC (n=10) reduced the antithrombotic effect of melagatran (FD 52% [+/-9%;
      P<0.002], PLD 61% [+/-17%; P=0.028] versus melagatran alone) at a dose (250 U/kg)
      that had no effect on the BT (327% [+/-150%; P=0.607]. Meanwhile, FVIIa (n=12)
      normalized the BT to 115% (+/-32%; P<0.05) at a dose (270 microg/kg) that was not
      yet prothrombotic (FD 26% [+/-4%; P<0.001], PLD 39% [+/-9%; P=0.970]).
      CONCLUSION: Administration of FVIIa during antithrombotic treatment with direct
      thrombin inhibitors might support hemostasis before promoting the intraluminal
      expansion of thrombi.

PMID- 16448688
TI  - Impact of preschool environment upon children's physical activity and sun
      exposure.
AB  - BACKGROUND: The physical qualities of outdoor environments are important to
      trigger healthy behavior in children. We studied the impact of outdoor
      environments upon spontaneous physical activity and exposure to ultraviolet (UV)
      radiation in 4- to 6-year-old children at 11 preschools in Stockholm county.
      METHODS: In May-June 2004, pedometry and measurement of UV radiation were carried
      out on 197 children from 11 preschools in Stockholm county. Outdoor environments
      differed regarding vegetation, topography, space, and education. Ambient global
      UV radiation data were collected, free sky, and ground surface assessed. Arrival,
      in- and outdoor stay, and departure were recorded. For analysis, linear mixed
      model analysis was applied. RESULTS: In environments with trees, shrubbery, and
      broken ground, the mean step count/min was 21.5, and mean exposure to UV
      radiation as fraction of available UV during play outdoors 14.6%. In delimited
      environments with little vegetation, the mean step count/min was 17.7 and mean
      exposure fraction to UV radiation 24.3% (P < 0.001, crude). Step/min range was
      8.9-30.0 (girls) and 8.8-37.2 (boys), UV radiation exposure range 4-60% (no
      difference between genders). CONCLUSION: Spacious preschool environments with
      trees, shrubbery, and broken ground trigger physical activity and yield sun
      protection in outdoor play. As many children attend preschool, access to such
      environments is recommended in community architecture.

PMID- 16448689
TI  - Effect of water storage on the impact strength of three glass fiber-reinforced
      composites.
AB  - OBJECTIVES: The effect of water sorption on the impact strengths of two pre
      impregnated fiber-reinforced composites (FRCs) and one impregnated FRC were
      studied. All FRCs were available clinically. METHODS: Eight 1.0 mm x 2.0 mm x
      25.0mm bar-shaped specimens of each material were prepared according to
      manufacturers' instructions. The impact strength of each specimen was tested
      (adoption from ISO 179-1 Plastics-Determination of Charpy impact properties)
      after the specimens were immersed in 23.0+/-1 degrees C distilled water for
      seven, 60 and 180 days. The data were analyzed using the Weibull method. Scanning
      electron micrographs were taken to examine the mode of failure. RESULTS: Weibull
      analysis of the B10 strength of the FRCs showed that the difference in impact
      strength for each FRC due to the duration of water immersion was not significant
      (P>0.05). The impact strength of pre-impregnated E-glass FRC (Vectris) (75
      kJ/m(2)) was not significantly different from the pre-impregnated S-glass FRC
      (FiberKor) (66 kJ/m(2)) (P>0.05). The impregnated FRC possessed impact strength
      (42 kJ/m(2)) that was not significantly different from the pre-impregnated S
      glass FRC but was significantly lower than the pre-impregnated E-glass FRC. x100
      SEMs of the three types of FRC specimens revealed fiber failure to be the
      predominant mode of failure. SIGNIFICANCE: Water immersion up to 180 days
      duration did not significantly affect the impact strength of three FRCs. The
      impact strength of the impregnated FRC was not significantly different from the
      pre-impregnated S-glass FRC but was significantly lower than the pre-impregnated
      E-glass FRC.

PMID- 16448690
TI  - Interactions and compatibility of 11 S globulin from Vicia faba seeds and sodium
      salt of carboxymethylcellulose in an aqueous medium.
AB  - This work studies specific interactions and compatibility between a legumin and a
      linear carboxylated polysaccharide using gel permeation chromatography,
      sedimentation analysis, SDS gel electrophoresis, viscometry and phase analysis
      measurements. It uses the system water/11 S globulin/CMC as a model.
      Carboxymethylcellulose (CMC) molecules are able to cause a partial dissociation
      of the protein, subsequent formation of soluble interbiopolymeric complexes and
      partial aggregation of the free non combined protein at room temperature and pH
      6.0-6.5. The maximal binding of biopolymers is observed at their equimolar ratio.
      The decrease in temperature of the mixture from 293 to 277 K leads to formation
      of the complex coacervate. The increase in pH from 6.0 to 7.6 results in
      suppression of complex formation and manifestation of the phenomenon of
      thermodynamic incompatibility if the total concentration of biopolymers in the
      system exceeds the critical concentration of segregative phase separation.

PMID- 16448691
TI  - Study on the interaction between 4-(2-diethylamino-ethylamino)-8-oxo-8H
      acenaphtho[1,2-b]pyrrole-9-carbonitrile and DNA by molecular spectra.
AB  - The binding geometry of a heterocyclic compound, 4-(2-diethylamino-ethylamino)-8
      oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (A1) to CT DNA was studied by
      molecular spectroscopy. Deduced from SYBR Green-DNA melt curve, UV-vis
      spectroscopy, and fluorescence studies, there were two different interaction
      mechanisms involved in the whole interaction process depending on the R-value (R,
      the molar ratio of A1 to CT DNA base pairs). The value R = 0.20 was the turning
      point. The induced circular dichroism (ICD) spectra of A1 complexed with CT DNA,
      poly[(G-C)2] and poly[(A-T)2] showed when R < or = 0.20, A1 intercalated into CT
      DNA and the intercalation orientation of A1 to the dyad axis of DNA double-helix
      was heterogeneous. When R > 0.20, stacking of A1 on surface helix of DNA occurred
      driven by the protonation of amidogen group in the N,N-diethyldiamine
      substitution of A1, which was illustrated by the changes of A1-DNA geometry in
      different pH solutions. The intrinsic circular dichroism (CD) spectra showed the
      conformation of DNA converted from the B-form to A-like conformation due to the
      A1 intercalation.

PMID- 16448692
TI  - DSTHO: database of siRNAs targeted at human oncogenes: a statistical analysis.
AB  - Existing treatments of human cancer, which is characterized by abnormal
      proliferation of cells often lead to fatal outcomes. Sequence selective silencing
      of oncogene expression using siRNA technology is emerging as a potential solution
      for cancer treatment. The exclusive selectivity and easy application to virtually
      any therapeutic target including intracellular factors and transcription factors
      renders siRNA oligonucleotide applications very promising. However, synthesis of
      siRNA having sufficient knockdown efficiency is laborious and cost intensive. The
      database is designed in order to aid the synthesis of siRNAs, which target human
      oncogenes (OsiRNAs). It provides OsiRNAs of known efficacy from previous
      experiments with links to published literature and theoretically pre-generated
      putative target sequences. In addition, links to available theoretical tools,
      databases and literature corresponding to siRNAs in general are also provided.
      The links to literature provide information about role of siRNA in therapeutics,
      chemical properties and transfection methods. Statistical analysis of mono-, di-
      and tri- mers located in OsiRNAs of known efficacies is performed to identify
      positional preferences and screen specific motifs. This analysis aids the design
      and synthesis of effective siRNAs, which particularly target human oncogenes. The
      database can be accessed at .

PMID- 16448693
TI  - How useful is SBF in predicting in vivo bone bioactivity?
AB  - The bone-bonding ability of a material is often evaluated by examining the
      ability of apatite to form on its surface in a simulated body fluid (SBF) with
      ion concentrations nearly equal to those of human blood plasma. However, the
      validity of this method for evaluating bone-bonding ability has not been assessed
      systematically. Here, the history of SBF, correlation of the ability of apatite
      to form on various materials in SBF with their in vivo bone bioactivities, and
      some examples of the development of novel bioactive materials based on apatite
      formation in SBF are reviewed. It was concluded that examination of apatite
      formation on a material in SBF is useful for predicting the in vivo bone
      bioactivity of a material, and the number of animals used in and the duration of
      animal experiments can be reduced remarkably by using this method.

PMID- 16448694
TI  - Synthesis and characterization of single-phase silicon-substituted alpha
      tricalcium phosphate.
AB  - Silicon-substituted calcium phosphate (CaP) powders with a Ca/(P+Si) ratio of
      1.50 have been prepared by a wet chemical method, with silicon contents up to
      2.16 weight percent (wt%). Sintering for 2 h at 1250 degrees C yields single
      phase silicon-substituted alpha tricalcium phosphate (Si-alpha-TCP) for
      compositions between 0.59 and 1.14 wt% silicon. The sintered powders have been
      characterized with X-ray fluorescence (XRF) spectrometry, X-ray diffraction
      (XRD), attenuated total reflection infrared spectroscopy (ATR-IR) and
      transmission electron microscopy (TEM). Compositions with less than 0.59 wt%
      silicon result in mixtures of Si-alpha-TCP, beta-TCP, and calcium hydroxyapatite
      (HA), while compositions with more than 1.14 wt% silicon result in mixtures of Si
      alpha-TCP and HA. The lattice parameters of single-phase Si-alpha-TCP prepared
      with 0.87 wt% silicon are a=12.874(1)A, b = 27.372(2) A, c = 15.225(1) A, and
      beta = 126.38(1) degrees .

PMID- 16448695
TI  - In vivo enhancement of sensory perception recovery in a tissue-engineered skin
      enriched with laminin.
AB  - The use of autologous reconstructed skin appears to be a promising treatment for
      the permanent coverage of deep and extensive burns. However, the capability of
      reconstructed skin transplanted on wounds to promote recovery of sensory
      perception is a major concern. Our aim was to assess the effect of laminin on
      cutaneous nerve regeneration. We prepared collagen-chitosan sponges enriched with
      0, 1, 10 or 50 microg of laminin/sponge to produce tissue-engineered
      reconstructed skins by culture of human fibroblasts and keratinocytes, then
      grafted on the back of athymic mice for 120 days. Immunohistochemical studies
      demonstrated that there were 7 times more neurofilament 150 kD-positive nerve
      fibers migrating in the graft in the samples enriched with 10 microg
      laminin/sponge, compared to reconstructed skin without laminin, 120 days after
      graft. A significant improvement in the current perception threshold of the Abeta
      and Adelta nerve fibers was measured using a Neurometer in all grafts enriched
      with laminin. In addition, the type C nerve fibers reached an identical current
      perception threshold than mouse skin, in all reconstructed skins enriched or not
      with laminin. We conclude that the use of a tissue-engineered autologous skin
      graft enriched with laminin has the potential to efficiently optimize cutaneous
      sensory nerve regeneration in vivo.

PMID- 16448697
TI  - Genomic imbalances and patterns of karyotypic variability in mantle-cell lymphoma
      cell lines.
AB  - Mantle-cell lymphoma (MCL) is genetically characterized by 11q13 chromosomal
      translocations involving the CCND1 gene. We have characterized five MCL cell
      lines, JVM-2, GRANTA-519, REC-1, JEKO-1, and NCEB-1, combining metaphase and
      array comparative genomic hybridization, multicolor-FISH, and molecular analysis.
      Our results revealed common gained regions at 2p14, 9q31.2-qter, 11q13.1-q21,
      13q14-q21.2, 13q34-qter and 18q21.1-q22.1, and losses at 1p21.2-p31.1, 2p11.2,
      8p21.2-pter, 9p21.3-pter, 11q23.3-qter, 17p11.2-pter, and 17q21.2-q22.2. All cell
      lines except JVM-2, displayed moderate or high numerical chromosome instability.
      In addition, an ongoing level of chromosome rearrangements was observed in REC-1.
      Surprisingly, NCEB-1 carried several stable mouse chromosomes and showed
      expression of both human and murine bcl-2 protein. Our findings indicate that
      these cell lines represent three patterns of chromosome evolution in MCL and may
      be useful to understand the pathogenesis of this neoplasm.

PMID- 16448696
TI  - Assessment of bone marrow mesenchymal stem cell biological characteristics and
      support hemotopoiesis function in patients with chronic myeloid leukemia.
AB  - Mesenchymal stem cells (MSCs) are of great therapeutic potential because of their
      ability to self-renew and differentiate into multiple tissues. Compare to
      allogenetic MSCs, autologous MSCs from patients needed cell-based therapy may be
      an ideal alternative stem cell source. However, characteristics of MSCs from a
      disease state are poorly understood. So, we have isolated and characterized MSCs
      from choronic myeloid leukemia (CML) patients and compared them with MSCs derived
      from normal adult bone marrow. Our results showed that CML derived MSCs are
      similar to normal MSCs in phenotype, morphology and multi-differentiation
      capacity. Moreover, CML derived MSCs did not express BCR/ABL gene and Ph
      chromosome, and had not the ability to development tumor in nude mice. At last,
      they could express hematopoietic cytokines, and possessed hematopoietic
      supportive ability. These findings indicate that MSCs derived from CML patients'
      bone marrow may be an attractive tool for clinical needs.

PMID- 16448698
TI  - The presence of the p53 transcripts with truncated open reading frames in Marek's
      disease tumor-derived cell lines.
AB  - Several kinds of the p53 transcripts in which their open reading frames (ORFs)
      were truncated (ranging from 101 to 765 bp) were identified in Marek's disease
      (MD)-derived tumor cell lines as well as avian leukosis- and
      reticuloendotheliosis-derived ones, detected by nested RT-PCR and subsequent
      nucleotide sequence analysis. In these ORFs, regions encoding the proline-rich
      and DNA-binding domains of the p53 protein were frequently deleted, and many of
      these deletions were found to cause frame shift. Western blot analysis using anti
      p53 monoclonal antibodies revealed that multiple p53 isoform proteins with
      various molecular weights including 45-46, 35 and 28 kDa were expressed in these
      tumor cell lines, though the p53 protein with a molecular weight of 49 kDa was
      detected in chicken embryo fibroblasts transformed by the SV40 T antigen as a
      control. Since no deletions were found in the p53 gene of these MD tumor cell
      lines, truncations in the p53 ORFs observed in this study might result from
      alternative splicing of the p53 gene.

PMID- 16448699
TI  - Forensic mental health law reform in Japan: from criminal warehousing to broad
      spectrum specialist services?
AB  - Since the 1980s Japan has undergone a number of mental health law reforms
      culminating in the 2005 forensic law. This added to its enactments on involuntary
      commitment, long-term aged care and substitute decision making, bringing Japan
      into focus as an industrialized state now possessed of a full package of civil
      and forensic provisions. This article seeks to demonstrate that the new forensic
      law cannot achieve its own stated goals without seeking to put into place
      financial and administrative supports aimed to integrate the myriad of patient
      populations that will be inevitably affected by the new forensic system. In order
      to avoid the widespread syndrome that has already been experienced
      internationally of warehousing mentally ill offenders in jails, it is critical
      that the Japanese government develop effective and culturally sensitive
      techniques for dealing with low risk populations through a diversionary process.
      Furthermore, although the legislation addresses serious crimes, it is imperative
      that policies be put into place to avoid directing young offenders, violent
      patients from the general hospital system, the developmentally handicapped,
      already convicted persons found in hospital settings and problematic cases in the
      correctional system, to the new forensic units established by the legislation. It
      is only though contemplating unintended outcomes of the legislation that the
      Japanese government will be able to avoid the ongoing stigmatization and
      prolonged institutionalization of mentally ill populations. Despite apparent
      cultural differences internationally vetted human rights requirements must be
      properly protected, not only in the forensic context, but throughout the mental
      health system at large. The coordination of services and the development of
      specialty training are necessary conditions for the realization of improved and
      humane conditions for mentally ill persons in Japan.

PMID- 16448700
TI  - Quantitative analysis of accuracy of an inertial/acoustic 6DOF tracking system in
      motion.
AB  - An increasing number of neuroscience experiments are using virtual reality to
      provide a more immersive and less artificial experimental environment. This is
      particularly useful to navigation and three-dimensional scene perception
      experiments. Such experiments require accurate real-time tracking of the
      observer's head in order to render the virtual scene. Here, we present data on
      the accuracy of a commonly used six degrees of freedom tracker (Intersense IS900)
      when it is moved in ways typical of virtual reality applications. We compared the
      reported location of the tracker with its location computed by an optical
      tracking method. When the tracker was stationary, the root mean square error in
      spatial accuracy was 0.64 mm. However, we found that errors increased over ten
      fold (up to 17 mm) when the tracker moved at speeds common in virtual reality
      applications. We demonstrate that the errors we report here are predominantly due
      to inaccuracies of the IS900 system rather than the optical tracking against
      which it was compared.

PMID- 16448701
TI  - Effect of repetitive transcranial magnetic stimulation on serum brain derived
      neurotrophic factor in drug resistant depressed patients.
AB  - BACKGROUND: Depression has been associated with low brain-derived neurotrophic
      factor (BDNF) serum levels, while antidepressant drugs appear to mend this
      alteration. The purpose of this study was to assess BDNF serum levels in drug
      resistant depressed patients before and after repetitive Transcranial Magnetic
      Stimulation (rTMS) antidepressant treatment. METHODS: BDNF levels were measured
      in serum of 16 resistant depressed patients using the ELISA technique. RESULTS:
      BDNF baseline levels showed a negative correlation with illness severity measured
      by HDRS scores (R = -0.517, p = 0.04) and a significant increase of serum BDNF
      was found after rTMS treatment (t = -2.549, df = 15, p = 0.022). CONCLUSIONS: Our
      findings support the relationship between decreased serum BDNF and depression
      symptomatology and suggest a normalizing effect of rTMS antidepressant treatment.
      Further replications in larger samples will help to clarify the relevance of this
      preliminary data in the rTMS mechanism of action.

PMID- 16448702
TI  - Psychopathology of panic attacks in panic disorder.
AB  - PURPOSE: This study examined the relationships among certain subtypes of panic
      attacks (full vs. limited symptom; spontaneous vs. situational) and between these
      subtypes, panic disorder subtypes, and other characteristics of panic disorder,
      especially agoraphobia. METHOD: Data were drawn from a large (n = 1,168)
      treatment study of panic disorder in which panic attacks were carefully subtyped
      and counted using a diary. Relationships between variables at baseline were
      examined primarily using non-parametric methods, and the course of improvement
      for panic subtypes among completers was plotted. RESULTS: The median number of
      spontaneous panic attacks per week at baseline was similar among patients with
      panic disorder without agoraphobia (PD), limited phobic avoidance (PDL), and
      agoraphobia (PDA). The median number of situational attacks and the median
      agoraphobia ratings rose progressively across diagnostic subtypes. Anticipatory
      anxiety, HAM-A, HAM-D, and disability scores were higher in PDA than in PD. Full
      and limited symptom panic attacks were positively correlated. The proportion of
      total attacks that were limited rose during the first two weeks of treatment,
      suggesting conversion of full to limited symptom attacks before complete
      disappearance. Spontaneous and situational attacks were correlated minimally or
      not at all. Agoraphobia ratings were more positively correlated with situational
      than with spontaneous panic attacks. Few of the correlations among measures at
      baseline were high. CONCLUSIONS: Full and limited symptom panic attacks differ
      primarily in severity. Spontaneous and situational attacks are relatively
      independent, and situational attacks are more closely related to agoraphobia.
      These findings are consistent with previous work suggesting that spontaneous
      attacks reflect a biological component, whereas situational attacks reflect a
      cognitive component in the psychopathology-- and possibly the pathogenesis-- of
      panic disorder. This provides a rationale for the use of combined pharmacotherapy
      and psychotherapy in the treatment of panic disorder. Future investigations of
      panic disorder should carefully separate panic attack subtypes.

PMID- 16448703
TI  - The 'drive for activity' and "restlessness" in anorexia nervosa: potential
      pathways.
AB  - This paper discusses the hypothesis that a 'drive for activity" in the presence
      of physiological and endocrine changes consistent with starvation is a
      characteristic symptom of acute anorexia nervosa (AN). This 'drive for movement',
      along with alertness and lack of fatigue, so unlike the motor slowing and loss of
      energy observed in simple starvation has been recognized in AN throughout
      history, but has received little attention in the past fifty years. Clinical
      reports and experimental evidence suggest that 'restlessness' and a 'drive for
      activity' vary in intensity, they appears to be starvation-dependent and to wane
      with food intake. Central nervous system (CNS) systems known to be involved in
      mediating activity and arousal levels that are altered by the negative energy
      expenditure in AN are reviewed. Among these, the corticotropin-releasing hormone
      (CRH) system, the melanocyte stimulating hormone/agouti-related protein
      (MSH/AGRP) system and the norepinephrine/epinephrine (NE/EPI) and dopamine (DA)
      system may contribute to the 'drive for activity' and alertness in AN. AN appears
      to represent a disorder of gene/environment interaction. Future research will
      reveal whether in individuals predisposed to AN, the 'drive for activity'
      reflects the reactivation of mechanisms important in food scarcity, controlled by
      one or more evolutionary conserved genes including those regulating foraging
      behavior. Recognition of the 'drive for activity' as a diagnostic symptom of AN
      and its assessment prior to re-nutrition would permit clarification of its role
      in the etiology of AN.

PMID- 16448704
TI  - Expression and role of Fc- and complement-receptors on human dendritic cells.
AB  - Dendritic cells (DCs) are professional antigen presenting cells, which take up
      pathogens/foreign structures in peripheral tissues, then migrate to secondary
      lymphoid organs where they initiate adaptive immune responses by activating naive
      T-cells. In the early phase of antigen uptake pattern recognition receptors
      (including mannose-, scavenger- and toll-like receptors) that recognize pathogen
      associated molecular patterns play an important role. Later receptors binding
      opsonized antigen are also involved in phagocytosis. These cell membrane
      molecules include various Fc-receptors, recognizing different isotypes of
      antibodies and various complement-receptors, such as CR3, CR4 and the C1q-binding
      complex of calreticulin and CD91. Here we aim to summarize how these
      immunecomplex binding receptors are involved in the initiation of DC maturation,
      and how they influence antigen presentation as well as some additional functions
      of these cells.

PMID- 16448705
TI  - NOS2 regulates cytokine production and VLA-4 expression in experimental
      autoimmune encephalomyelitis.
AB  - Inducible nitric oxide synthase (NOS2) expression in the central nervous system
      correlates with EAE disease activity. Inhibition of NOS2 ameliorates adoptively
      transferred EAE, yet exacerbates actively induced EAE. Herein, the
      encephalitogenicity of T cells induced by immunization in the presence or absence
      of NOS2 was examined. Upon passive transfer, T cells from myelin oligodendrocyte
      glycoprotein-immunized NOS2-deficient C57BL/6 mice induced more severe EAE than T
      cells from wild-type mice. The heightened encephalitogenicity of NOS2-/- T cells
      correlated with enhanced expression of VLA-4 (CD49d) and increased production of
      interferon gamma and tumor necrosis factor. NO plays an important regulatory role
      in autoimmune T cell induction.

PMID- 16448706
TI  - The nasal septum deformities in children and adolescents from Warsaw, Poland.
AB  - OBJECTIVE: The final shape of the nasal septum deformities is a result of
      irregular development of the nasomaxillary complex or of a nasal injury. Nasal
      septum deformities reveal in childhood. The aim of this study is to estimate the
      prevalence of the particular types of the septum deformities in children
      according to Mladina's classification, analysis of the correlation between types
      of deformities and age and sex and checking if nasal injury influences the
      occurrences of nasal septum deformities and determines the particular type of it.
      METHODS: The nasal septum morphology was examined in 288 children aged 3-17. The
      investigation was performed in kindergartens and schools in Warsaw. The study
      population was divided into three groups. Anterior rhinoscopy without nasal
      vasocontrictive drugs was performed. A questionnaire was included. The nasal
      septum deformities were qualified according to Mladina's classification. Analysis
      of variance (ANOVA) and Wilcoxon's test were used to performed statistical
      significance. RESULTS: Deviation of the nasal septum was diagnosed in nearly 34%
      of the sample population. The nasal septum deformities occurred in 29% of girls
      and in nearly 37% of boys. The prevalence of septum deformities in group 1 aged 3
      7 years was 35.23%, in group 2 aged 8-13 years was 27.97% and in group 3 aged 14
      17 years was 40.24%. We observed statistically significant correlation between
      age of patients and type of nasal septum deformities (F=3.65, p=0.000876). In
      children with nasal injures, 66.66% had nasal septum deformities while in group
      without injuries there was about 31.69%. We observed statistically significant
      correlation between type of nasal septum deformities and nasal injuries (Z=7.67,
      p<0.0000001). CONCLUSIONS: The percentage of the nasal septum deformities change
      with age. Deviation of the nasal septum was more prevalent in boys. The risk of
      occurrence of the nasal septum deformities increases after nasal injury. Type 1
      and type 5 according to Mladina's classification dominates in study population.
      Type 1 decreases with age, while type 5 increases with age.

PMID- 16448707
TI  - Larengopharengeal reflux in patients with severe adeno-tonsil hyperplasia.

PMID- 16448708
TI  - Identification and analysis of fitness of resistance mutations against the HCV
      protease inhibitor SCH 503034.
AB  - HCV NS3 protease variants resistant to the protease inhibitor SCH 503034 were
      selected. Three mutations, T54A, V170A and A156S mutations conferred low to
      moderate levels of resistance (<20-fold). Longer exposure (>10 passages) or
      selection with higher levels of compound led to the selection of a more resistant
      variant, A156T (>100-fold). [Lin, C., Lin, K., Luong, Y.P., Rao, B.G., Wei, Y.Y.,
      Brennan, D.L., Fulghum, J.R., Hsiao, H.M., Ma, S., Maxwell, J.P., Cottrell, K.M.,
      Perni, R.B., Gates, C.A., Kwong, A.D., 2004. In vitro resistance studies of
      hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: structural
      analysis indicates different resistance mechanisms. J. Biol. Chem. 279(17), 17508
      17514; Lu, L., Pilot-Matias, T.J., Stewart, K.D., Randolph, J.T., Pithawalla, R.,
      He, W., Huang, P.P., Klein, L.L., Mo, H., Molla, A., 2004. Mutations conferring
      resistance to a potent hepatitis C virus serine protease inhibitor in vitro.
      Antimicrob. Agents Chemother. 48(6), 2260-2266.] Combination with IFN-alpha
      drastically reduced the number of emergent colonies. Resistant colonies showed no
      change in sensitivity to IFN-alpha. Although the A156T mutation conferred the
      highest level of resistance to SCH 503034, it significantly reduced the colony
      formation efficiency (CFE) of the mutant replicon RNA, and rendered replicon
      cells less fit than those bearing wild-type replicons. Replicon cells bearing
      mutation A156S were less fit than wild-type in co-culture growth competition
      assays but showed no impact on CFE. The V170A mutation, on the other hand, did
      not affect replicon fitness in either assay, which was consistent with its
      emergence as the dominant mutant after 12 months of continuous selection. The
      reduced fitness of the most resistant variant suggests that it may be rare in
      naive patients and that development of high-level resistance may be slow.
      Combination therapy with IFN-alpha should also greatly reduce the potential
      emergence of resistance.

PMID- 16448709
TI  - Soluble semicarbazide sensitive amine oxidase (SSAO) catalysis induces apoptosis
      in vascular smooth muscle cells.
AB  - Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of
      primary aromatic and aliphatic amines. It is selectively expressed in vascular
      cells of blood vessels, but it is also circulating in blood plasma. SSAO activity
      in plasma is increased in some diseases associated with vascular complications
      and its catalytic products may cause tissue damage. We examined the effect of the
      oxidation of the SSAO substrate, methylamine, on cultured smooth muscle cells.
      Cell incubation with methylamine plus soluble SSAO, contained in bovine serum,
      resulted toxic to rat aorta A7r5 and human aortic smooth muscle cells, as
      measured by MTT reduction. This effect was completely reverted by specific SSAO
      inhibitors, indicating that the toxicity was mediated by the end products
      generated. Moreover, SSAO-mediated deamination of methylamine induced apoptosis
      in A7r5 cells, detected by chromatin condensation, Caspase-3 activation, PARP
      cleavage and cytochrome c release to cytosol. Formaldehyde, rather than H2O2,
      resulted to be a strong apoptotic inducer to A7r5 cells. Taken together, the
      results suggest that increased plasma SSAO activity in pathological conditions,
      could contribute to apoptosis in smooth muscle cells, leading to vascular tissue
      damage.

PMID- 16448710
TI  - Phosphorylation of NF-kappaB1/p105 by oncoprotein kinase Tpl2: implications for a
      novel mechanism of Tpl2 regulation.
AB  - The oncoprotein kinase Tpl2 plays an essential role in macrophage activation by
      the bacterial component lipopolysaccharide (LPS). In response to LPS stimulation,
      Tpl2 phosphorylates a downstream kinase, MEK1, leading to the activation of ERK
      signaling pathway. Recent studies demonstrate that the NF-kappaB1 precursor
      protein p105 functions as an inhibitor of Tpl2 and that the LPS-stimulated Tpl2
      activation requires p105 degradation. However, how p105 inhibits the signaling
      function of Tpl2 is not completely understood. We show here that p105 does not
      inhibit the intrinsic kinase activity of Tpl2. When complexed with p105, Tpl2
      remains catalytically active and uses p105 as a substrate. However, the p105
      bound Tpl2 is unable to phosphorylate its physiological target, MEK1. These
      findings suggest that p105 functions as a competitive inhibitor of Tpl2 that
      blocks its access by MEK1.

PMID- 16448711
TI  - Relationship of serum leptin concentration with age, gender, and biomedical
      parameters in healthy, non-obese subjects.
AB  - It is known that the circulating levels of leptin, the adipocyte hormone
      implicated in the control of energy balance, are correlated with fat body mass
      (FBM), although the influences of other physiological conditions are not fully
      understood. We investigated the relationships of serum leptin concentration with
      age, gender, and 36 hormone-metabolic parameters in a sample of a well defined
      healthy population (n=246; age range 20-93 years), and in subgroups of lean
      individuals according to their body mass index (BMI), within similar age range
      and gender distribution. Only insulin secretion (positively) and testosteronemia
      (negatively, in males) show direct correlations. The other relationships are not
      significant but throughout collaborating variables, such as serum lipids,
      especially through FBM, lean body mass (LBM) through insulin secretion, and
      gender through FBM. In males, LBM correlates with insulin secretions, s-IGF-1 and
      with s-testosterone. The relationship between insulin secretion and LBM persists
      up to advanced age. From the present study it may be concluded that the positive
      relationship of leptin with insulin secretion and the negative one with
      testosterone, indicate direct implications of leptin in insulin signaling, as
      well as in male sexual development. Finally, the fact that the amount of secreted
      insulin depends on LBM and the latter on testosterone and IGF-1, indicates the
      importance of muscle mass in the control of insulin secretion.

PMID- 16448712
TI  - Response to Ivarie: Competitive bioreactor hens on the horizon.

PMID- 16448713
TI  - Involvement of neurotrophic factors in aging of noradrenergic innervations in
      hippocampus and frontal cortex.
AB  - In the present study, we investigated the age-dependent changes in the axon
      terminals of the locus coeruleus (LC) neurons in the frontal cortex and
      hippocampus, in which a high degree of axonal branching in the middle-aged brain
      was suggested to occur in our previous electrophysiological study. We used 6-, 13
      and 25-month-old male F344/N rats, and performed Western blot analysis of the
      norepinephrine transporter (NET), brain-derived neurotrophic factor (BDNF) and
      glial cell line-derived neurotrophic factor (GDNF). NET expression level
      increased in the 13-month-old hippocampus, but was not altered by aging in the
      frontal cortex. BDNF expression level increased in the hippocampus, but did not
      change with age in the frontal cortex. On the other hand, GDNF expression level
      was increased with age in the frontal cortex, but was not in the hippocampus.
      These results suggest that the LC noradrenergic innervations may be locally
      regulated by different neurotrophic factors that exert their trophic actions at
      different target sites.

PMID- 16448714
TI  - Plant expression of chicken secretory antibodies derived from combinatorial
      libraries.
AB  - Delivery of secretory IgA antibodies (sIgA) to mucosal surfaces is a promising
      strategy to passively prevent infectious diseases. Plants have been proposed as
      biofactories for such complex immunoglobulin molecules. Recently, the molecular
      characterization of all four monomers of chicken sIgA (IgA immunoglobulin heavy
      and light chains, J-chain and secretory component) has been completed, allowing
      recombinant, up scaled production of chicken sIgA and extension of passive immune
      strategies to poultry. To test the suitability of the plant cell factory for bulk
      production of chicken sIgA, we studied the expression of chicken IgA, dIgA and
      sIgA in planta. To that end, new cassettes were designed that allowed the
      grafting of immunoglobulin variable regions derived from combinatorial libraries
      into full-size chicken IgA frames ready for plant expression. Using this system,
      10 individual phage display clones, which had previously been selected against
      Eimeria acervulina antigens, were transferred "from phage to plant". Plant-made
      chicken antibodies showed strong differences in expression levels, which seemed
      governed mainly by the stability of their respective light chains. Finally, with
      the co-expression of chicken IgA heavy and light chains, J-chain and secretory
      component in N. benthamiana leaves we showed that plant cells are suitable
      biofactories for the production of assembled chicken sIgA complexes.

PMID- 16448715
TI  - The human cytomegalovirus-encoded receptor US28 increases the activity of the
      major immediate-early promoter/enhancer.
AB  - The activation of the major immediate-early promoter (MIEP) is a key event in the
      cytomegalovirus replication cycle and is dependent on cellular transcription
      factors which are partially activated by viral proteins. Expression of the viral
      chemokine receptor homolog US28 results in constitutive activation of pro
      inflammatory transcription factors that may be involved in the activation of the
      major immediate-early promoter/enhancer. Using reporter gene assays in human
      embryonic kidney cells, we found that US28 signaling was responsible for
      increased major immediate-early promoter/enhancer activity which was independent
      of beta-chemokine binding. Inhibition of nuclear factor-kappaB (NF-kappaB) only
      partially blocked the effect of US28, whereas treatment with a specific p38
      mitogen activated kinase (MAPK) inhibitor fully abrogated the US28-induced
      enhancement of promoter activity. Our results suggest that during human
      cytomegalovirus (HCMV) infection, US28 in epithelial cells transactivates the
      major immediate-early promoter/enhancer via the activation of p38 MAPK and
      downstream signaling that partially involves NF-kappaB.

PMID- 16448716
TI  - Macro- and microcirculation in the lower extremities--possible relationship.
AB  - AIMS: Impaired blood supply is a significant risk factor for diabetic foot
      ulceration and gangrene. A possible relationship between peripheral
      macroangiopathy and the spectral components of microvascular skin blood flow in
      the lower extremities was tested in diabetic patients (DP) and non-diabetic
      subjects (C). PATIENTS AND METHODS: Basal skin blood flow (BSBF) was recorded for
      30min at the right and left medial malleolus (predominantly nutritive capillary
      circulation) by laser Doppler flowmetry in 64 DP and 31 C. Its oscillatory
      components were analyzed using wavelet transform. Peripheral arterial
      obliterative disease (PAOD) was defined according to ankle/brachial index (ABI):
      PAOD+ (ABI<0.9: 21 DP, 12 C), PAOD- (ABI 0.91-1.3: 43 DP, 19 C). RESULTS: No
      statistically significant differences in BSBF and its oscillatory components were
      observed between PAOD+ and PAOD-, neither in DP nor in C. In DP, the spectral
      component of microvascular flow associated with endothelial activity was in
      significant positive correlation with systolic pressures on brachial and dorsal
      pedal artery (p=0.001 and 0.010, respectively). CONCLUSIONS: These results
      indicate that mean BSBF and its oscillatory components do not change with
      diabetic PAOD; however there is a strong correlation between systolic pressure
      and the oscillatory components of BSBF related to endothelial activity manifested
      in the frequency interval 0.0095-0.02Hz.

PMID- 16448718
TI  - Controls on atrazine leaching through a soil-unsaturated fractured limestone
      sequence at Brevilles, France.
AB  - The objective of this study was to identify the main controls on atrazine
      leaching through luvisols and calcisols overlying fissured limestone using the
      dual-permeability model MACRO. The model parameterisation was based on a
      combination of direct measurements (e.g. hydraulic properties, adsorption and
      degradation), literature data and calibration against bromide leaching
      experiments in field plots. A Monte Carlo sensitivity analysis was carried out
      for a typical application pattern, considering two different depths of
      unsaturated limestone (15 and 30 m). MACRO calibrations to the field experiments
      demonstrated the occurrence of strong macropore flow in the luvisol, while
      transport in the calcisol could be described by the advection-dispersion
      equation. MACRO simulations of tritium and atrazine leaching qualitatively
      matched tritium concentration profiles measured in the limestone and atrazine
      concentrations measured in piezometers and in aquifer discharge via a spring. The
      sensitivity analysis suggested that the thickness of the limestone, as well as
      the transport properties and processes occurring in the unsaturated rock (e.g.
      matrix vs. fissure flow) will have little significant long-term effect on
      atrazine leaching, mainly because degradation is very slow in the limestone. No
      mineralization of atrazine was detected in one-year incubations and a mean half
      life of 10 years was assumed in the simulations. Instead, processes occurring in
      the soil exerted the main control on predicted atrazine leaching, especially
      variations in the degradation rate and the strength of sorption and macropore
      flow. However, fissure flow in unsaturated rock is expected to exert a much more
      significant control on groundwater contamination for compounds that degrade more
      readily in the deep vadose zone.

PMID- 16448719
TI  - Is there evidence for recommending needleless closed catheter access systems in
      guidelines? A systematic review of randomized controlled trials.
AB  - A systematic review was conducted to determine whether certain vascular access
      policies are better than others in terms of prevention of catheter-related
      infections. Publications were retrieved by a search of Medline, the Cochrane
      Library and Embase up to May 2005. All randomized trials and systematic
      reviews/meta-analyses of randomized trials evaluating the effect of vascular
      access policies (i.e. needleless closed systems, conventional closed systems or
      conventional open systems) on catheter-related infection in hospitalized patients
      with intravascular catheters in situ were selected. Two reviewers independently
      assessed trial quality and extracted data. Data from the original publications
      were used to calculate the relative risk or the incidence-density relative rate
      of catheter-related infection. Data for similar outcomes were combined in the
      analysis where appropriate using a random-effects model. Of the six studies
      reviewed, one was excluded. Five randomized controlled trials were included in
      the review. The quality of the trials and the way they were reported were
      generally unsatisfactory. Four trials compared needleless closed systems with
      conventional open systems. There was a trend for an advantage of the needleless
      closed devices in terms of less catheter-associated bloodstream infection, less
      catheter tip colonization and less hub inlet colonization. There were no
      possibilities for combining data because of clinical heterogeneity. One trial
      compared needleless closed systems with conventional closed systems and the
      evidence was inconclusive. From the point of view of infection prevention, there
      are no objections to use these new systems. However, there is insufficient
      evidence at this stage to recommend the needleless closed vascular devices.

PMID- 16448720
TI  - Pseudomonas aeruginosa producing VIM-2 metallo-beta-lactamases and carrying two
      aminoglycoside-modifying enzymes in China.

PMID- 16448721
TI  - On the wrong scent: banning fresh flowers from hospitals.

PMID- 16448722
TI  - Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal
      18F-FDG-PET-study.
AB  - OBJECTIVE: To identify the pattern of progression of decline of cerebral glucose
      metabolism in frontotemporal dementia (FTD, frontal variant). METHODS: 22
      patients with mild FTD underwent 18F-FDG-positron emission tomography at baseline
      and at follow-up in average 19.5 months later. Patient scans were compared with
      scans from 15 healthy age-matched control subjects on a voxel-by-voxel basis
      using SPM-99. RESULTS: As compared with healthy control subjects at baseline
      patients with FTD showed a significant symmetrical hypometabolism of the frontal
      lobes sparing the motor cortex, of the caudate nuclei, insula and thalamus
      bilaterally. At follow-up further significant reductions in glucose metabolism
      were observed in the parietal and temporal cortices. CONCLUSIONS: In early stages
      of FTD the neurodegenerative process is limited to the frontal lobes. During the
      progression of the disease, the pathological changes pass over the lobar borders
      and spread into the parietal and temporal cortices.

PMID- 16448723
TI  - Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged
      Tg2576 mice.
AB  - Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology.
      Here, the effects of the antioxidant, alpha-lipoic acid (ALA) were tested on the
      Tg2576 mouse, a transgenic model of cerebral amyloidosis associated with AD. Ten
      month old Tg2576 and wild type mice were fed an ALA-containing diet (0.1%) or
      control diet for 6 months and then assessed for the influence of diet on memory
      and neuropathology. ALA-treated Tg2576 mice exhibited significantly improved
      learning, and memory retention in the Morris water maze task compared to
      untreated Tg2576 mice. Twenty-four hours after contextual fear conditioning,
      untreated Tg2576 mice exhibited significantly impaired context-dependent
      freezing. ALA-treated Tg2576 mice exhibited significantly more context freezing
      than the untreated Tg2576 mice. Assessment of brain soluble and insoluble beta
      amyloid levels revealed no differences between ALA-treated and untreated Tg2576
      mice. Brain levels of nitrotyrosine, a marker of nitrative stress, were elevated
      in Tg2576 mice, while F2 isoprostanes and neuroprostanes, oxidative stress
      markers, were not elevated in the Tg2576 mice relative to wild type. These data
      indicate that chronic dietary ALA can reduce hippocampal-dependent memory
      deficits of Tg2576 mice without affecting beta-amyloid levels or plaque
      deposition.

PMID- 16448725
TI  - Solution focused nursing: an evaluation of current practice.
AB  - This Australian study explored the extent to which solution focused nursing
      (SFN), a new philosophy of care underpinning a Bachelor of Nursing Programme, was
      understood by students and staff. Students and faculty perceptions of teaching
      and learning were explored using survey and semi-structured interview methods.
      The results showed that students did not have strong views about whether
      solutions or problems contribute best to a definition of nursing knowledge, but
      there were some differences between the year groups. This was hypothesised to be
      related to the way SFN is or is not being taught. Teachers were generally
      positive about SFN but perceived that they needed more education on the
      philosophy to ensure it could be translated into their teaching. A teaching and
      learning package is recommended to be produced and made available to all teachers
      within the program.

PMID- 16448726
TI  - pDNAVACCultra vector family: high throughput intracellular targeting DNA vaccine
      plasmids.
AB  - DNA vaccines have the potential to provide a safe route for protective immunity
      to neoplasms and infectious agents. However, current DNA vaccine plasmids are not
      optimal with additional non-essential DNA, nor do they facilitate controlled or
      flexible targeting of antigens to various intracellular destinations. A family of
      DNA vaccine vectors, optimized and minimized to comply with FDA guidelines
      regarding content and elimination of extraneous materials, was constructed. The
      resulting vectors are much smaller than existing vectors, drive higher levels of
      target gene expression, facilitate high throughput cloning applications, and
      allow simultaneous cloning into multiple vectors that feature various
      intracellular targeting destinations for the protein product. The ability to
      control expression and trafficking is intended to provide a rapid, rational
      approach to cancer therapy and emerging infectious diseases.

PMID- 16448724
TI  - Alpha2beta1 and alphaVbeta1 integrin signaling pathways mediate amyloid-beta
      induced neurotoxicity.
AB  - Pathological hallmarks of Alzheimer's disease are the presence of extracellular
      amyloid plaques, intracellular neurofibrillary tangles, and neurodegeneration.
      The principal component of amyloid plaques is the amyloid-beta peptide (Abeta).
      Accumulating evidence indicates that Abeta may play a causal role in Alzheimer's
      disease. In this report, we demonstrate that Abeta deposition and neurotoxicity
      in human cortical primary neurons are mediated through alpha2beta1 and
      alphaVbeta1 integrins using specific integrin-blocking antibodies. An aberrant
      integrin signaling pathway causing the neurotoxicity is mediated through Pyk2.
      The role of alpha2beta1 and alphaVbeta1 integrins can be extended to another
      amyloidosis using an amylin in vitro neurotoxicity model. These results indicate
      that the alpha2beta1 and alphaVbeta1 integrin signaling pathway may be critical
      components of neurodegeneration in Alzheimer's disease and that integrins may
      recognize and be activated by a shared structural motif of polymerizing
      amyloidogenic proteins.

PMID- 16448727
TI  - Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.
AB  - The absence of standard guidelines from National and International regulatory
      agencies for the safety evaluation of biotechnology products challenges the
      ingenuity of toxicologists. At present, the development of standard pre-clinical
      toxicology protocols for such products is on an individual case basis. The
      present investigation is an attempt to evaluate the safety profile of the first
      indigenously developed DNA based anti-rabies vaccine in India. The test compounds
      were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV
      (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical
      use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory
      requirements, the study has been designed to undertake acute (single dose--10
      days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose-
      120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x
      therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss
      Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on
      affinity and rapid higher antibody response during the efficacy studies. Apart
      from physical, physiological, clinical, hematological and histopathology profiles
      of all target organs, the tier-I immunotoxicity parameters have also been
      monitored. There were no observational adverse effects even at levels of 10x
      therapeutic dose administration of DRV and CRV. The procedure also emphasizes on
      the designing of protocols for the products developed by recombinant technique.

PMID- 16448728
TI  - Yellow fever vaccination: some thoughts on how much is enough [Vaccine 23 (2005)
      3908-3914].
AB  - In a recently published article in this journal, Massad et al. contraindicates
      yellow fever vaccination to persons 60 years or older, considering that the risk
      of serious adverse events is higher for this age class. The conclusion was based
      on the input of available data on age-related probabilities of developing serious
      adverse events in the United States, as well on other data not firmly
      established. We consider such contraindication inadequate, because the data input
      has limitations, higher letality of wild-type yellow fever infection in older
      adults, risk of introduction of yellow fever by travelers into new countries,
      lower risk of vaccine adverse events in revaccinated or immune people in endemic
      countries, and the experience of Brazil, with only one suspect case of associated
      viscerotropic disease in an individual older than 60 years. The model proposed by
      Massad et al. is useful but can lead to different conclusions, depending on the
      epidemiological context and individual risk profile.

PMID- 16448729
TI  - Leishmania donovani: identification of stimulatory soluble antigenic proteins
      using cured human and hamster lymphocytes for their prophylactic potential
      against visceral leishmaniasis.
AB  - Most of the studies for the identification of prophylactic antigens that elicit T
      cell responses were concentrated on membrane proteins of Leishmania donovani.
      This study was taken up to assess L. donovani soluble promastigote antigens for
      their ability to stimulate proliferation of peripheral blood mononuclear cells
      (PBMCs) from cured visceral leishmaniasis (VL) patients, endemic and non-endemic
      controls and lymphocytes/peritoneal macrophages of cured hamsters. The soluble
      protein was subjected to sequential precipitation with saturated ammonium
      sulphate (20%, 40%, 60% and 80%), of which largely 80% fractioned protein showed
      significant cellular responses in cured patients and hamsters. This fraction was
      further fractionated into five sub fractions by preparative SDS-PAGE and
      subjected to re-evaluation for their ability to induce cellular responses. Out of
      these, only F2 sub fraction belonging to the MW of 97.4-68 kDa stimulated
      remarkable lymphoproliferative and IFN-gamma responses in cured VL patients and
      in endemic controls. Similarly, significant lymphoproliferative responses and
      nitric oxide production were also noticed in cured Leishmania infected animals
      indicating an element of uniformity in responses between hamster and human. F2
      sub fraction, when evaluated for its prophylactic efficacy with BCG against L.
      donovani challenge in hamster exhibited significant parasite inhibition in spleen
      (71.1%; p<0.001) and liver (68.2%; p<0.001) as compared to their unvaccinated
      counterpart. The vaccinated animals showed significant lymphoproliferative
      response and nitric oxide production but leishmania specific IgG level were
      suppressed. The results indicate the presence of immunostimulatory and protective
      molecules in F2 sub fraction which may further be exploited for the development
      of a vaccine against VL, hitherto an unrealized goal.

PMID- 16448730
TI  - Oral immunization of mice using transgenic tomato fruit expressing VP1 protein
      from enterovirus 71.
AB  - Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease
      associated with fatal neurological complications in young children, and several
      major outbreaks have occurred recently. This study developed an effective
      antiviral agent by transforming the gene for VP1 protein, a previously defined
      epitope and also a coat protein of EV71, into tomato plant. VP1 protein was first
      fused with sorting signals to enable it to be retained in the endoplasmic
      reticulum of tomato plant, and its expression level increased to 27 microg/g of
      fresh tomato fruit. Transgenic tomato fruit expressing VP1 protein was then used
      as an oral vaccine, and the development of VP1-specific fecal IgA and serum IgG
      were observed in BALB/c mice. Additionally, serum from mice fed transgenic tomato
      could neutralize the infection of EV71 to rhabdomyosarcoma cells, indicating that
      tomato fruit expressing VP1 was successful in orally immunizing mice. Moreover,
      the proliferation of spleen cells from orally immunized mice was stimulated by
      VP1 protein, and provided further evidence of both humoral and cellular immunity.
      Results of this study not only demonstrate the feasibility of using transgenic
      tomato as an oral vaccine to generate protective immunity in mice against EV71,
      but also suggest the probability of enterovirus vaccine development.

PMID- 16448731
TI  - Development of tolerance against toxic Microcystis aeruginosa in three
      cladocerans and the ecological implications.
AB  - This is the first experimental study to compare difference in the development of
      tolerance against toxic Microcystis among multi-species of cladocerans (Daphnia,
      Moina and Ceriodaphnia) pre-exposed to two M. aeruginosa PCC7820 strains (MC
      containing and MC-free). Zooplankton were divided into S population (fed
      Scenedesmus), M-F population (fed Scenedesmus+MC-free Microcystis), and M-C
      population (fed Scenedesmus+MC-containing Microcystis). M-F and M-C populations
      were pre-exposed to Microcystis strains for 4 weeks, and their newborns were
      collected for experiments. A pre-exposure to MC-containing or MC-free Microcystis
      increased tolerance against toxic Microcystis. The marked increases in survival
      rate and median lethal time (LT(50), 100-194% increase) in the M-C population of
      Ceriodaphnia suggest that small-sized cladocerans may develop stronger tolerance
      against Microcystis than large-sized ones when both groups are exposed to toxic
      Microcystis. This may explain why dominant Daphnia is usually replaced by small
      sized cladocerans when cyanobacteria bloomed in summer in eutrophic lakes.

PMID- 16448732
TI  - Identifying source correlation parameters for hydrocarbon wastes using compound
      specific isotope analysis.
AB  - A preliminary evaluation of compound-specific isotope analysis (CSIA) as a novel,
      alternative method for identifying source correlation compounds in soils
      contaminated with residual heavy or weathered petroleum wastes is presented. Oil
      contaminated soil microcosms were established using soil (sandy-loam, non
      carbonaceous cley) amended with ballast-, crude- or No.6 fuel oil. Microcosms
      were periodically sampled over 256 days and delta(13)C values (which express the
      ratio of (13)C to (12)C) determined at each time point for five n-alkanes and the
      isoprenoid norpristane using gas chromatography-isotope ratio mass spectrometry
      (GC-IRMS). Although some temporal variation was observed, no significant temporal
      shifts in the delta(13)C values for the five n-alkanes were measured in all three
      oils. Isoprenoid isotope ratios (delta(13)C) appeared to be least affected by
      biotransformation, especially in the No.6 fuel oil. The research suggests that
      the delta(13)C of isoprenoids such as norpristane, may be of use as source
      correlation parameters.

PMID- 16448733
TI  - Modelling trace metal partitioning in forest floors of northern soils near metal
      smelters.
AB  - Trace metal (TM) mobility and toxicity varies with changing soil conditions.
      Geochemical models can account for the influence of soil characteristics on TM
      behaviour. We tested the effectiveness of the Stockholm humic model (SHM), and
      the NICA-Donnan model (NDM) to estimate partitioning coefficients (logKd) in 26
      forest floor horizons of podzolic soils enriched in trace metals from deposition
      by metal smelters. We wanted to know if a consistent approach could be applied to
      model metal partitioning in forest floors without optimizing each individual
      soil. When optimized, the SHM reproduced the partitioning of Cd, Cu and Zn but
      not Pb. It was necessary to revise the affinity constants for the NDM to
      simultaneously simulate the partitioning of the four metals. Revised affinity
      constants for the NDM model based on a fixed definition of soil organic carbon,
      i.e., a fixed ratio of fulvic and humic acids per unit carbon, reproduced metal
      partitioning more effectively in an independent data set of 16 soils than the use
      of generic affinity constants available for these models. From the perspective of
      the applicability of these models to risk assessment, this result suggests
      geochemical models using affinity constants that have been verified and/or
      modified against multiple soils from a region can provide good estimates of metal
      partitioning on a regional scale.

PMID- 16448734
TI  - What is the preimplantation embryo?
AB  - We present results from our 'bioethical field studies', which explore and compare
      the views of experts, patients and the general public on the beginning of human
      life and the status of the preimplantation embryo in Germany. Using a qualitative
      and quantitative multi-method approach, we found crucial differences in the
      categorization of the beginning of human life within the expert group
      (representative samples of human geneticists n=104, ethicists n=168, midwives
      n=294, obstetricians n=147, paediatricians n=166), and between expert and lay
      samples (IVF couples n=108, high genetic risk couples n=324, general population
      n=1017). The majority of lay respondents as well as paediatricians and
      obstetricians chose nidation, the moment when the implantation of the fertilized
      egg into the uterus takes place, as the crucial boundary that marks the beginning
      of human life, whereas the majority of (female) human geneticists, ethicists and
      midwives voted for conception as the decisive point in time. The views of all
      groups on the status of the preimplantation embryo differed from the assumptions
      underlying German legislation (Embryo Protection Act). Religiousness and
      religious affiliation, gender, attitudes towards disabled people, post-material
      values and a present desire for a child were identified as independent factors
      influencing attitudes towards the preimplantation embryo in the population
      sample. The results are discussed within a broader philosophical and social
      science perspective of constructivism versus essentialism, proposing a truly
      interdisciplinary approach to such bioethical core issues as new reproductive
      technologies and the status of the preimplantation embryo.

PMID- 16448735
TI  - Influence of education and knowledge on perceptions and practices to control
      malaria in Southeast Nigeria.
AB  - The study was undertaken in southeastern Nigeria to investigate whether the
      people's level of education and what they know about malaria affects how they
      seek treatment and prevention for the disease. Pre-tested questionnaires were
      used to collect data from randomly selected householders and analysed using
      logistic regression. Higher levels of education were associated with improved
      knowledge and practice about the appropriate strategies for the prevention and
      treatment of malaria. The results thus indicate that education can have a
      positive impact on the malaria burden and medium/long-term improvement of overall
      literacy rates. As well as this, short-term health education campaigns about the
      causes, manifestations and control of malaria will have a positive impact on its
      control.

PMID- 16448737
TI  - Comparative responses of rats and mice exposed to linear/branched, linear, or
      branched ammonium perfluorooctanoate (APFO).
AB  - The purpose of this study was to compare the toxicity of linear/branched ammonium
      perfluorooctanoate (APFO) with that of linear and branched APFO. Linear/branched
      APFO (approximately 80% linear and 20% branched isomers) was formerly used in the
      production of commercial products. The extensive toxicologic database for APFO
      has been developed essentially using this mixture of isomers. The trend now is to
      use APFO containing only the linear isomer. The current study was performed to
      determine if the toxicological database developed for the linear/branched isomer
      is applicable to the linear isomer. To determine the contribution of branched
      APFO to the toxicity of linear/branched APFO, a form of APFO that was 100%
      branched was synthesized. Rats and mice were given doses by oral gavage ranging
      from 0.3 to 30 mg/kg of either the linear/branched, linear, or branched APFO for
      14 days. Clinical signs, body weights, food consumption, selected hematology and
      serum lipid parameters, liver and kidney weights, hepatic peroxisomal beta
      oxidation, and serum PFOA concentrations were evaluated. Mean body weights were
      about 20% lower in rats and mice dosed with 30 mg/kg of linear/branched or linear
      APFO compared to controls, and 3-5% lower in animals dosed with 30 mg/kg of
      branched APFO. In rats, all three forms reduced lipids. In mice, all three forms
      reduced total and HDL cholesterol similarly but triglycerides were increased at
      lower doses. Increased peroxisomal beta-oxidation activity and serum PFOA
      concentrations were seen in both species but these effects were least pronounced
      in rats dosed with the branched material. In rats, serum PFOA levels were 20-51
      ppm at Lowest Observed Effect Levels (LOEL) of 0.3-1 mg/kg, based primarily upon
      lipid parameters. In mice, serum PFOA levels were 10-14 ppm at the LOEL of 0.3
      mg/kg, based primarily upon relative liver weight. In both rats and mice, the
      overall responses to the linear/branched and the linear forms of PFOA were
      similar, but the branched form appears to be less potent. Based on these results,
      and for the endpoints evaluated in this study, the toxicological database
      developed primarily from testing linear/branched APFO is applicable to linear
      APFO.

PMID- 16448738
TI  - Time course and mechanisms of hemoconcentration in response to mental stress.
AB  - Hemoconcentration with mental stress exposure may be involved in the triggering
      of acute cardiovascular events. In the present study, hematocrit was measured
      repeatedly at baseline, during a 4 min mental stress task and during 20 min of
      recovery. Blood was sampled every 1-2 min throughout. Blood pressure, heart rate
      and R-wave to pulse interval, a measure of cardiac contractility, were measured
      with the same periodicity. The stress task elicited a 1.3% increase in
      hematocrit, which was sustained with full return to baseline level occurring only
      after 16 min of recovery. Between-subject correlations between hematocrit and
      hemodynamic activity were low. Aggregate within-subject coefficients were more
      impressive; the temporal profile of hematocrit correlated significantly with all
      hemodynamic variables. Similar within-subject analyses indicated that whereas
      cardiac contractility was correlated with hematocrit both during stress-related
      increase and subsequent recovery, blood pressure was related to hematocrit only
      during the increase. This suggests that stress-induced hemoconcentration may
      driven by different mechanisms than those which underlie its recovery.

PMID- 16448740
TI  - Needle core length is a quality indicator of systematic transperineal prostate
      biopsy.
AB  - OBJECTIVE: To analyse the length of needle cores sampled as a quality indicator
      in systematic transperineal prostate biopsy. We assessed the correlation of core
      length with the other clinical and topographic parameters. MATERIAL AND METHODS:
      We prospectively evaluated data from 509 consecutive patients who underwent a
      first set of transrectal ultrasound-guided transperineal prostate biopsy for
      suspected prostate cancer. Fourteen cores were sampled from each patient. Needle
      cores were stretched and placed in tissue cassettes between two nylon meshes
      according to the pre-embedding methods of prostate needle biopsy specimens. For
      single biopsy core, the measurement of length (in millimetres) and any percentage
      of cancer in the biopsy specimen were reported. RESULTS: The mean length of 7,126
      analysed cores was 14.14+/-4.35mm. All cores were longer than 10mm. The mean
      length of needle cores sampled did not correlate with patient age, total prostate
      specific antigen value, digital rectal examination, and prostate volume. The
      whole mean length of the six samples from the peripheral zone of the right lobe
      was higher than the mean corresponding value of the six samples from the left
      lobe peripheral zone (p<0.001). The transperineal approach allows a greater
      sampling of the prostate apex than of the midgland and prostate base (p<0.001).
      CONCLUSIONS: The length of the needle cores sampled during transperineal prostate
      biopsy fulfils the parameters of quality required by pathologists for an
      appropriate evaluation of the biopsy specimen.

PMID- 16448739
TI  - Are low doses of enoxaparin with aspirin sufficient to guarantee good gestational
      outcome in women with heterozygote factor V Leiden mutation?

PMID- 16448741
TI  - Involvement of novel PKC isoforms in FFA induced defects in insulin signaling.
AB  - Involvement of novel PKCs (nPKCs) in the negative regulation of insulin-signaling
      pathway is a current interest of many workers investigating the cause for insulin
      resistance and type 2 diabetes. Free fatty acids (FFAs) are recently shown to be
      the major players in inducing insulin resistance in insulin target cells. They
      are also found to be involved in activating nPKCs associated with the impairment
      of insulin sensitivity. In this overview, we describe PKC delta, theta and
      epsilon linked to the FFA induced damage of insulin-signaling molecules.

PMID- 16448742
TI  - Protein kinase C mediated phosphorylation blocks juvenile hormone action.
AB  - Juvenile hormones (JH) regulate a wide variety of developmental and physiological
      processes in insects. Although the biological actions of JH are well documented,
      the molecular mechanisms underlying JH action are poorly understood. We studied
      the molecular basis of JH action using a JH response element (JHRE) identified in
      the promoter region of JH esterase gene cloned from Choristoneura fumiferana,
      which is responsive to JH and 20-hydroxyecdysone (20E). In Drosophila
      melanogaster L57 cells, the JHRE-regulated reporter gene was induced by JH I, JH
      III, methoprene, and hydroprene. Nuclear proteins isolated from L57 cells bound
      to the JHRE and exposure of these proteins to ATP resulted in a reduction in
      their DNA binding. Either JH III or calf intestinal alkaline phosphatase (CIAP)
      was able to restore the binding of nuclear proteins to the DNA. In addition,
      protein kinase C inhibitors increased and protein kinase C activators reduced the
      binding of nuclear proteins to the JHRE. In transactivation assays, protein
      kinase C inhibitors induced the luciferase gene placed under the control of a
      minimal promoter and the JHRE. These data suggest that protein kinase C mediated
      phosphorylation prevents binding of nuclear proteins to juvenile hormone
      responsive promoters resulting in suppression of JH action.

PMID- 16448743
TI  - Kaurene diterpenes from Laetia thamnia inhibit the growth of human cancer cells
      in vitro.
AB  - Four ent-kaurene diterpenes were isolated from the leaves of Laetia thamnia L.:
      ent-kaur-16-en-19-oic acid (1a), ent-3beta-hydroxykaur-16-ene (2), ent-kaur-16-en
      3alpha,19-diol (3a), and ent-17-hydroxykaur-15-en-19-oic acid (4). The methyl
      ester (1b) of compound 1a and the acetate diester (3b) of compound 3a were
      prepared, and all compounds were evaluated for cytotoxicity against human
      prostate (22Rv1, LNCaP), colon (HT29, HCT116, SW480, SW620), and breast (MCF-7)
      tumor cells at concentrations ranging from 6 to 50microg/mL. The kaurenes showed
      activity in all cell lines tested, with the prostate cells demonstrating the most
      sensitivity as follows: 22 Rv1 cells towards 1a (IC(50) 5.03microg/mL) and 1b
      (IC(50) 6.81microg/mL), and LNCaP towards 2 (IC(50) 12.83microg/mL) and 4 (IC(50)
      17.63microg/mL).

PMID- 16448744
TI  - Integrin-mediated cell-matrix interactions for prosurvival and antiapoptotic
      signaling after genotoxic injury.
AB  - Interactions of cells with their microenvironment modify the cellular sensitivity
      of normal and tumor cells for radiation- and drug-induced genotoxic injury. The
      preexistent or acquired cellular resistance against such agents aggravates
      anticancer therapies and, therefore, complicates the recovery of patients.
      Recently, integrin-mediated adhesion was shown to improve cell survival of both
      normal and cancer cells following DNA damage. Here, I will discuss the role of
      integrins and integrin-mediated signaling cascades in the survival or death
      response upon genotoxic stress. Detailed knowledge of the responsible molecular
      processes might provide implications for putative therapies targeting integrins
      or integrin-associated molecules to achieve an optimization of anticancer
      treatments.

PMID- 16448745
TI  - A synergic inhibitory-effect of combination with selective cyclooxygenase-2
      inhibitor and S-1 on the peritoneal metastasis for scirrhous gastric cancer
      cells.
AB  - An inhibitory-effect of a selective cyclooxygenase-2 (COX-2) inhibitor on
      peritoneal metastasis of scirrhous gastric carcinoma was investigated in vivo.
      Peritoneal metastasis had developed after intraperitoneal inoculation of
      scirrhous gastric cancer cells, OCUM-2MD3, in nude mice. COX-2 inhibitor and/or S
      1 were administered orally in nude mice with peritoneal metastasis. Oral
      administration of COX-2 inhibitor and S-1 significantly prolonged survival rates
      of these nude mice, compared with either alone. These findings suggested that
      combining S-1 and COX-2 inhibitor administration obtain a synergistic inhibitory
      effect on the peritoneal metastasis of scirrhous gastric carcinoma.

PMID- 16448747
TI  - Regulation of p21/ras protein expression by diallyl sulfide in DMBA induced
      neoplastic changes in mouse skin.
AB  - Diallyl sulfide (DAS), a naturally occurring organosulfide, present in garlic, is
      known to possess pleiotropic biological effects. DAS is known to inhibit
      chemically induced tumors in a number of animal models. The chemopreventive
      properties of DAS seem to occur through a number of mechanisms, but its role on
      primary events on oncogenic activation is not well understood. In the present
      study, we demonstrated the modulatory effect of DAS on the expression of H-ras
      gene product, p21/ras protein as one of the mechanisms of its chemopreventive
      action in chemically induced mouse skin tumors. Our results showed that DAS
      administration leads to modulation of the DMBA-induced levels of p21/ras
      oncoprotein as early as 24h after the DMBA application, suggesting down
      regulation of the p21/ras by DAS. Furthermore, the modulatory effects of DAS were
      also evident in DMBA-induced mouse skin tumors. DAS administration led to
      increase in the levels of cytosolic p21/ras and decrease in the levels of p21/ras
      in membrane fractions. DAS administration was also found to down regulate the
      DMBA-induced H-ras mRNA level in mouse skin tumors. The immunohistochemical
      staining of the skin/tumor showed 55.82 and 46.86% decrease in the area positive
      for p21/ras expression levels in DAS pre- and post-supplemented groups,
      respectively. Flow-cytometric analysis, further confirms our results as indicated
      by a shift in the mean fluorescence intensity (MFI) towards lower fluorescence in
      DAS administered groups in comparison to the DMBA treated group. Thus, one
      mechanism of the growth inhibitory properties of DAS is through the suppression
      of development of tumors that harbor ras mutations by inhibiting the membrane
      association of oncogenic p21/ras protein.

PMID- 16448746
TI  - Lower level of BRCA2 protein in heterozygous mutation carriers is correlated with
      an increase in DNA double strand breaks and an impaired DSB repair.
AB  - The BRCA2 protein is involved in the maintenance of genomic stability through its
      key role in homologous recombination repair of DNA double strand breaks.
      Biallelic inactivation of BRCA2 leads to a defect in DNA repair and is associated
      with a chromosomal instability phenotype. Recent studies on familial breast
      cancer clusters revealed chromosomal rearrangements and higher rates of sister
      chromatid exchanges also in heterozygous BRCA2 mutation carriers. In the present
      study, lymphoblastoid cell lines of heterozygous BRCA2 mutation carriers and of
      wildtype relatives were compared with regard to BRCA2 mRNA and protein expression
      and capacity to repair DNA damage induced by gamma-irradiation and mitomycin C.
      BRCA2+/- cells showed lower amounts of the full-length BRCA2 protein compared to
      BRCA2+/+ cells. The kinetics of gamma-H2AX protein level revealed distinct
      defects in DNA double strand break repair in the BRCA2+/- cells. These results
      are indicative of a haploinsufficiency phenotype in BRCA2+/- cells, suggesting
      that reduced amounts of functional BRCA2 protein in BRCA2+/- carriers are
      insufficient for an efficient repair of DNA double strand breaks, a condition
      that could contribute to the impairment of genomic stability.

PMID- 16448749
TI  - Do people with Parkinson's disease change strategy during unplanned gait
      termination?
AB  - In light of the movement control problems reported for patients with Parkinson's
      disease (PD), we examined the lower extremity control strategies used by these
      subjects to stop walking in planned and unplanned situations. We compared how
      patients with PD and age and gender-matched control subjects modulated lower
      extremity muscular activity and ground reaction forces during planned and
      unplanned stoppings. The main findings were that control subjects did not alter
      muscle activation from planned to unplanned stopping, relative to stance limb
      kinetic events; they just increased the amplitude of the response (by
      approximately 800%). We speculate that these data provide preliminary evidence in
      support of a stereotypical sequence of muscle activation for gait termination
      whether planned or unplanned. In contrast, subjects with PD appeared to adopt a
      different strategy when stopping unexpectedly compared to planned stopping.
      Additional data show that subjects with PD required additional steps to stop
      walking when stopping unexpectedly as compared to control subjects.

PMID- 16448748
TI  - Long-term effect of early discharge on sEPSC and [Ca2+]i in developing neurons.
AB  - To study the long-term changes induced in immature rat cortical neuronal cultures
      by transient exposure to an Mg(2+)-free treatment, at cultured day 6, cells were
      assigned into three groups, based on the mediums they were transiently exposed to
      as follows: control group 1 (CONT1) was exposed to Dulbecco's Modified Eagle's
      Medium (DMEM), control group 2 was exposed to a physiological solution (PS), and
      the magnesium-free physiological solution group (MGFPS) was exposed to the same
      medium as CONT2 except for the removal of magnesium. Following a 3-h exposure,
      the amplitude and frequency of spontaneous excitatory postsynaptic currents
      (sEPSC) were recorded and intracellular calcium concentrations ([Ca2+]i) were
      measured. Compared to the CONT1 and CONT2 groups, the MGFPS group displayed a
      significantly greater amplitude (at d6, d7, d9, and d12) and frequency (at d6,
      d7, and d9) of sEPSC (p<0.05). Also, both the resting and peak intracellular
      calcium levels were significantly greater in the MGFPS group at days 6, 7, 9, 12
      and 17 (p<0.05). The rise time (time from resting level to peak level of
      intracellular calcium following NMDA application) was significantly shorter in
      the MGFPS group at culture days 7 and 17 and significantly longer at culture day
      12 (p<0.05). Finally, we compared the percentage of cortical neurons expressing
      neuron-specific enolase (NSE) and found that there were no significant
      differences in the number of NSE positive neurons among three groups at days 7,
      12, and 17. Our results suggests that there are long-term changes in sEPSCs and
      [Ca2+]i in cultured rat cortical neurons following exposure to Mg2+-free
      environment without cell loss.

PMID- 16448750
TI  - GSM radiation triggers seizures and increases cerebral c-Fos positivity in rats
      pretreated with subconvulsive doses of picrotoxin.
AB  - This study investigated the effects of mobile-phone-type radiation on the
      cerebral activity of seizure-prone animals. When rats transformed into an
      experimental model of seizure-proneness by acute subconvulsive doses of
      picrotoxin were exposed to 2 h GSM-modulated 900 MHz radiation at an intensity
      similar to that emitted by mobile phones, they suffered seizures and the levels
      of the neuronal activity marker c-Fos in neocortex, paleocortex, hippocampus and
      thalamus increased markedly. Non-irradiated picrotoxin-treated rats did not
      suffer seizures, and their cerebral c-Fos counts were significantly lower.
      Radiation caused no such differences in rats that had not been pretreated with
      picrotoxin. We conclude that GSM-type radiation can induce seizures in rats
      following their facilitation by subconvulsive doses of picrotoxin, and that
      research should be pursued into the possibility that this kind of radiation may
      similarly affect brain function in human subjects with epileptic disorders.

PMID- 16448751
TI  - Loose ligation of the sciatic nerve in rats elicits transient up-regulation of
      Homer1a gene expression in the spinal dorsal horn.
AB  - Changes in the expression of many genes underlie injury-elicited plasticity in
      the spinal dorsal horn. Homer1 is a recently identified gene that appears to play
      a critical role in the expression of synaptic plasticity in several brain
      regions, including the hippocampus. In this study we investigated the early
      consequences of chronic constriction injury of the sciatic nerve on Homer1 gene
      expression in the spinal dorsal horn. Significant increases in Homer1a mRNA
      levels in the ipsilateral dorsal horn were detected at 4h post-ligation, and
      these levels remained elevated at 8h before returning to baseline values by 24h
      after the ligation. In contrast, the levels of Homer1b/c mRNA did not change at
      any of these selected post-ligation times. The ligation-associated induction of
      Homer1a was dependent on activation of NMDA receptors and the extracellular
      signal-regulated kinase 1 and 2 (ERK1/2) pathway. The non-competitive NMDA
      receptor antagonist, MK-801, and a specific inhibitor of the ERK1/2 pathway,
      U0126, significantly attenuated the injury-elicited increases in Homer1a mRNA
      when compared to saline-treated animals. These data provide the first evidence
      for a potential role of Homer1a in peripheral nerve injury-elicited plasticity in
      the spinal dorsal horn. These data also imply that the early and transient up
      regulation of Homer1a gene expression may be an important contributor to the
      eventual development of neuropathic pain.

PMID- 16448752
TI  - Switching-on and -off of bistable spontaneous discharges in rat spinal deep
      dorsal horn neurons.
AB  - Somatosensory deep dorsal horn spinal neurons were previously shown to present in
      vitro a bistable state of activity in which a fixed firing rate is maintained
      over prolonged periods in the absence of stimulation. Those periods of enhanced
      spinal spontaneous discharge may play a role in the genesis or maintenance of
      hyperalgesic states, where episodes of durable spontaneous pain are commonly
      reported. Here we show in vivo that a small percentage of deep spinal neurons (4%
      of the recorded population) are capable of rapidly shifting between low-frequency
      and high-frequency levels of spontaneous activity. At least one of the
      transitions between the two states was induced by stimulation of the receptive
      field, making this an interesting and unique case in which stable firing rates
      are switched-on or -off by somatosensory stimuli.

PMID- 16448753
TI  - NMDA receptor/L-VGCC-dependent expression and AMPA/KA receptor-dependent
      activation of c-Jun induced by cerebral ischemia in rat hippocampus.
AB  - Over-activation of ionotropic glutamate receptors can cause an excessive influx
      of calcium ions into neurons, which subsequently triggers the degeneration and
      death of cells in a process known as excitotoxicity. Here, we examined the
      effects of modulating ionotropic glutamate receptors and L-type voltage-gated
      calcium channels (L-VGCC) on the expression and activation of c-Jun in
      hippocampus of SD rats after transient global ischemia. The total protein of c
      Jun was altered by ischemia-reperfusion and reached its high levels at 3-6 h of
      reperfusion. However, the increased expression was prevented by pretreatment of
      ketamine (a non-competitive N-methyl-D-aspartate (NMDA) receptors antagonist) or
      nifedipine (a blocker of L-VGCC), but not by 6,7-dinitroquinoxaline-2,3(1H,4H)
      dione (DNQX), an AMPA/KA receptor antagonist. On the other hand, c-Jun
      phosphorylation was significantly increased 3 h after reperfusion, which was
      inhibited by DNQX, but not ketamine or nifedipine. AP-1 binding activity
      reactions were also performed by electrophoretic mobility shift assay (EMSA),
      which detected similar results as those in Western blotting. Our results clearly
      showed that c-Jun expression is NMDA receptor/L-VGCC-dependent and c-Jun
      activation is AMPA/KA receptor-dependent, which expands our knowledge of the JNK
      c-Jun signaling pathway in ischemic brain damage.

PMID- 16448754
TI  - After-effects of transcranial direct current stimulation (tDCS) on cortical
      spreading depression.
AB  - Abnormal cortical excitability influences susceptibility to cortical spreading
      depression (CSD) in migraine. Because transcranial direct current stimulation
      (tDCS) is capable of inducing lasting changes of cortical excitability, we
      investigated the after-effects of tDCS on the propagation velocity of CSD in the
      rat. Twenty-five anesthetised rats received either anodal, cathodal or sham tDCS.
      The stimulation was applied for 20 min at a current strength of 200 microA after
      the recording of three baseline CSD measurements. Starting 5 min after tDCS, a
      further three CSDs were elicited and CSD velocity recorded at intervals of 20
      min. tDCS and CSD recording was performed under anaesthesia with chloralose and
      urethane. As compared to the baseline velocity of 3.14 mm/min, anodal tDCS
      induced a significant increase of propagation velocity during the first post-tDCS
      recording (3.49 mm/min). In contrast to anodal tDCS, neither cathodal tDCS nor
      sham tDCS, which consisted of an initial ramped DC stimulation lasting only 20 s,
      showed a significant effect on CSD propagation velocity. As anodal tDCS is known
      to induce a lasting increase of cortical excitability in the clinical setting,
      our results support the notion that CSD propagation velocity reflects cortical
      excitability. Since cortical excitability and susceptibility to CSD is elevated
      in migraine patients, anodal tDCS - by increasing cortical excitability - might
      increase the probability of migraine attack in these patients, even beyond the
      end of its application.

PMID- 16448755
TI  - Contact mechanics and tip shape in AFM-based nanomechanical measurements.
AB  - Stiffness-load curves obtained in quantitative atomic force acoustic microscopy
      (AFAM) measurements depend on both the elastic properties of the sample and the
      geometry of the atomic force microscope (AFM) tip. The geometry of silicon AFM
      tips changes when used in contact mode, affecting measurement accuracy. To study
      the influence of tip geometry, we subjected ten AFM tips to the same series of
      AFAM measurements. Changes in tip shape were observed in the scanning electron
      microscope (SEM) between individual AFAM tests. Because all of the AFAM
      measurements were performed on the same sample, variations in AFAM stiffness-load
      curves were attributed to differences in tip geometry. Contact-mechanics models
      that assumed simple tip geometries were used to analyze the AFAM data, but the
      calculated values for tip dimensions did not agree with those provided by SEM
      images. Therefore, we used a power-law approach that allows for a nonspherical
      tip geometry. We found that after several AFAM measurements, the geometry of the
      tips at the very end is intermediate between those of a flat punch and a
      hemisphere. These results indicate that the nanoscale tip-sample contact cannot
      easily be described in terms of simple, ideal geometries.

PMID- 16448756
TI  - Molecular characterization of feline Hepatozoon species from Brazil.
AB  - Feline Hepatozoon species from Brazil was molecular identified and characterized
      for the first time in Sao Paulo state, Brazil. Partial sequences of the 18S rRNA
      gene from the Hepatozoon from three naturally infected cats were analyzed.
      Sequences revealed that feline Hepatozoon was closely related to the canine
      Hepatozoon canis from Brazil.

PMID- 16448757
TI  - Occurrence of Libyostrongylus sp. (Nematoda) in ostriches (Struthio camelus
      Linnaeus, 1758) from the north region of the state of Rio de Janeiro, Brazil.
AB  - Domestic production of ostrich in Brazil started in the beginning of the last
      decade, but its sanitary state has not been reported. Libyostrongylus sp. is an
      ostrich specific nematode whose parasitism can severely affect the birds. Thus,
      Libyostrongylus spp. larvae were identified in commercial ostriches in the north
      region of the state of Rio de Janeiro, Brazil. The EPG was determined and fecal
      cultivation was performed. The eggs presented typical characteristics of
      strongylid and were present in five out of six farms. The mean EPG varied from 22
      to 2395 and Libyostrongylus spp. prevalence was from 0 to 100%, with adult birds
      more infected. Two types of infective larvae with tail finishing in a tipped
      spiny knob were distinguished. The first had a mean length of 848 microm (710
      1010) with a long sheath tail of about 66 microm (52-112). The other had a mean
      length of 826 microm (620-940) with a short, more abruptly ending sheath tail of
      32 microm (22-40) and a less rounded cephalic end. The differences between these
      larvae suggest two Libyostrongylus species.

PMID- 16448758
TI  - Vertebrate freezing survival: Regulation of the multicatalytic proteinase complex
      and controls on protein degradation.
AB  - The wood frog, Rana sylvatica, survives weeks of whole body freezing during
      winter hibernation, expressing numerous metabolic adaptations that deal not only
      with freezing but with its consequences including organ ischemia and cellular
      dehydration. The present study analyzes the 20s multicatalytic proteinase (MCP)
      complex from skeletal muscle to determine how protein degradation is managed in
      the ischemic frozen state. MCP was partially purified and assayed
      fluorometrically using three AMC-labeled substrates to compare multiple states:
      control (5 degrees C acclimated), 24 h frozen at -2.5 degrees C, 4 or 8 h thawed
      at 5 degrees C, 8 h anoxia, and 40% dehydration. MCP from frozen frogs showed
      significantly different K(m) and V(max) values compared with controls; e.g., K(m)
      Z-LLE-AMC increased by 45% during freezing and 52% under anoxia whereas V(max)
      decreased by 40%. After thawing, K(m) was restored and V(max) rose by 2.2-fold.
      Incubations promoting protein kinase or phosphatase action on MCP showed that
      phosphatase treatment strongly increased V(max) implicating reversible
      phosphorylation in MCP regulation during freeze-thaw. Western blotting showed a
      36% decrease in MCP protein in muscle from frozen frogs. The 20s MCP
      preferentially degrades oxidatively-damaged proteins and evidence of impaired
      function during freezing came from a 1.4-fold increase in protein carbonyl
      content in muscle and liver during freezing. Ubiquitin and ubiquitin conjugate
      levels were unchanged in muscle but changed markedly in liver during freeze-thaw.

PMID- 16448759
TI  - Skin cell isolation and expansion for cell transplantation is limited in patients
      using tobacco, alcohol, or are exhibiting diabetes mellitus.
AB  - The aim of this exploratory study was to investigate the isolation and expansion
      of keratinocytes and fibroblasts from donors with certain medical histories.
      Biopsies were taken from donors (N=32) falling into one or more of the following
      categories: a history of heavy smoking and/or alcohol abuse, drug abuse, diabetes
      mellitus or steroid treatment. Cells from donors who did not fall into any of the
      above-mentioned categories were used as controls. Proliferation and growth
      behaviour of cells were analyzed by measurement of passage duration, absorbance
      (MTT-assay) and light microscopy. Donors with a specific medical history required
      larger biopsy areas than the control group for isolating a sufficient number of
      fibroblasts and keratinocytes. Times to confluence were significantly prolonged
      and absorbances (MTT) were significantly reduced in several donor groups when
      compared to control cultures. Biopsies from donors with steroid treatment, drug
      abuse and combined nicotine and alcohol abuse could not be established beyond
      passage 0 degrees or 1 degree, respectively. We conclude that isolation and
      expansion of skin cells from donors with certain medical histories may require
      larger biopsies, prolonged expansion times or may even result in failure. These
      findings may therefore be of clinical importance in the field of autologous skin
      cell transplantation.

PMID- 16448760
TI  - Paediatric burn prevention: an epidemiological approach.
AB  - OBJECTIVE: To study the mechanism of burn in hospitalized paediatric burn
      patients in order to develop a focused burn prevention campaign. METHODS: Acute
      paediatric burn patients were identified from the unit admission records.
      Detailed medical records were reviewed to identify the key demographic and
      management information including the country of residence, age, gender, extent of
      injury, specific treatment and hospital stay. Parents were then contacted to
      provide detailed information about the mechanism of the accident, first aid
      given, living density and parent's educational level. RESULTS: Two hundred and
      eighty-four admissions were identified in a 5-year period. Two hundred and twenty
      four of these patients came from a defined regional population served by the
      hospital. The median age of patients was 3 and male to female ratio 1:0.74. The
      most common age group for burns was 1-2 years. The most common type of burns were
      scalds. Domestic burns accounted for 84.7% of admissions. Median burn area was 4%
      of the total body surface area with a range of 0.2-45%. Fifty percent of patients
      had no first aid treatment prior to presentation at the hospital. More accidents
      happened in homes with a high living density and the majority of parents had both
      completed secondary education. The most dangerous location in the house was the
      living room, followed by the bathroom, kitchen then bedroom. The majority of
      burns were related to hot drinks, followed by hot food and then bathing.
      CONCLUSION: Detailed investigation of burn incidents can reveal repeated
      mechanisms of injury, which direct the focus of preventive strategies.

PMID- 16448761
TI  - Skin wound healing in the first generation (F1) offspring of Yorkshire and red
      Duroc pigs: evidence for genetic inheritance of wound phenotype.
AB  - Fibroproliferative scars in humans often demonstrate familial inheritance
      patterns, and genetics may contribute to healing and scarring. Genetic factors
      may also influence the scarring phenotype in a porcine model. Healing of full
      thickness excisional skin wounds in Yorkshire pigs closely resembles normal
      healing in humans, while identical wounds in red Duroc pigs form hypercontracted,
      hyperpigmented scars. The present study has evaluated the healing process in the
      first generation cross (F1) of red Duroc and Yorkshire pigs. Gross and histologic
      analysis revealed that the F1 animals exhibit an intermediate healing phenotype,
      with some features of each parent breed. F1 full thickness wounds were
      significantly hypercontracted and fibrotic, but apigmented. Analysis of mRNA
      expression patterns for a panel of relevant molecules (N=32) in the F1 animals
      revealed some similarities to each parent breed, as well as unique patterns for
      other molecules. Furthermore, a depth dependency to the healing response was
      observed at the gross, histologic, and molecular levels, with deep dermal wounds
      healing similar to Yorkshire wounds. These findings suggest that the genetic
      contribution to scar phenotype in this animal model is complex. However, the
      results indicate that further understanding in this model may provide insights
      into risk factors for hypertrophic scarring in human burn patients.

PMID- 16448762
TI  - Stenotrophomonas maltophilia bacteremia in burn patients.
AB  - Stenotrophomonas maltophilia has been increasingly reported as a nosocomial
      opportunistic pathogen in debilitated patients, including burn patients. There
      is, however, only one published report in English that discusses S. maltophilia
      bacteremia in burns. We performed a retrospective chart review and statistical
      analysis of the incidence, the duration of hospital stays before a diagnosis of
      bacteremia, antimicrobial susceptibility, prognosis, and mortality risk factors
      in burn patients. From January 1996 to December 2004, 14 episodes of S.
      maltophilia bacteremia in 13 of 666 patients admitted to the burn center at our
      hospital were identified. The patients, nine males and four females, ranged in
      age from 1 to 76 years (mean: 42.9+/-24.4 years). Eleven injuries were from flame
      burns and two were from scald burns. The mean total burned surface area (TBSA)
      was 47+/-30.2% and mean prognostic burn index (PBI) was 81.7+/-31.3. The average
      annual incidence was 2.3 episodes per 1000 admissions, and no outbreak cluster
      was noticed. The mean hospital stay before bacteremia was 19.8+/-11.9 days. Most
      isolates were susceptible to ticarcillin-clavulanate (87.5%) and moxalactam
      (85.7%). The overall mortality was 30.7% (4/13) and correlated significantly with
      TBSA (P<0.01) and PBI (P<0.05). The incidence of S. maltophilia bacteremia was
      higher in hospitalized burn patients than in hospitalized non-burn patients.
      Different antimicrobial susceptibility patterns may exist, especially in
      different geographic regions. Awareness of the possibility of infection by this
      opportunistic pathogen and commencement of adequate antibiotics treatment,
      especially after 3 weeks of intensive care, should be incorporated into the
      strategy of treatment in major burn patients.

PMID- 16448763
TI  - Burns in pregnancy.
AB  - A 9-year prospective study of burns in pregnant women hospitalized at the Sina
      hospital burn center was conducted to determine the etiology and outcome of
      pregnant patients. Fifty-one patients (27.45% self-inflicted, 72.55%
      unintentional) were identified and stratified by age, burn size, presence or
      absence of inhalation injury, trimester of pregnancy, maternal and fetal
      mortality, and cause of burn. The mean patient age was 24.2 years. There were 20
      maternal deaths and 23 fetal deaths. The majority of which (maternal: 13 and
      fetal: 13) were among self-inflicted burned pregnant women. The mean burn size
      was 37.7%, and was significantly larger for nonsurvivors of mother than survivors
      (68.8% versus 17.6%; p<0.001). In the 51 pregnant women, as the total burned body
      surface area exceeds 40%, both maternal and fetal mortality reaches 100%.
      Inhalation injuries were strongly associated with large burns, and were presents
      in all suicide patients. Kerosene ignition (68.6% of all patients, 100% of self
      inflicted patients) was the most common type of burn. Large burn size was the
      strongest predictor of mortality of mother and fetus followed by the presence of
      inhalation injury.

PMID- 16448764
TI  - Experience with elastic rubber bands for the tie-over dressing in skin graft.
AB  - We derived a dressing using elastic rubber bands to tie over the skin graft. This
      is a simple, easy to perform, timesaving, inexpensive and reliable method for
      applying pressure over the skin graft compared with traditional methods. Between
      September 2002 and August 2004, we have used the present dressing technique in 35
      patients with 36 grafts in various parts of the body. We chose this method,
      because of some anatomic areas, such as back, and buttock, which are frequently
      quite difficult to maintain pressure dressings in place, minimal movement can
      cause the skin graft to dislodge. The elastic rubber bands, rather than threads,
      are used as tie-over. Such a dressing permits expansion and contraction,
      providing a dynamic quality in the most difficult anatomic locations. The patient
      group consisted of 23 males and 12 females. The age ranged from 34 to 82 years
      (mean 52.4 years). Defect size ranged from 3x2.5 to 30x20 cm2 (mean 11.2x7.0 cm2
      in size). The average follow-up was 5.8 months (range: 1-12 months). Among the 36
      grafts in our study, all grafts except four showed good to excellent results. The
      mean graft successful rate is 88%. With our procedure no hematoma formation or
      shearing force (except one case) occurred in this group of patients during the
      phase of revascularization, there was, hence, good fixation of the graft by the
      "tie-over" dressing using elastic rubber bands compared with conventional tie
      over dressing, especially in skin grafts of the back site of body and at large
      graft area. However, it is not suitable for the potentially infectious
      granulation beds, especially near joint area.

PMID- 16448765
TI  - Coverage of scalp defects following contact electrical burns to the head: a
      clinical series.
AB  - Fifteen patients with various scalp defects resulting from contact electrical
      burns to the head, were reconstructed between the periods of January 1989 and
      October 2004 in our burns unit. The incidence of scalp burns in our patient
      population was 2.99% for electrical injuries and 0.95% for all burns during the
      study period. We present here a clinical series of fifteen patients with large,
      complex scalp defects following contact electrical burns to the head treated
      successfully by the application of local and free flaps. In this series, four
      free flaps, one pedicled flap and 10 local flaps were used for the
      reconstructions with no major postoperative complications seen. The average size
      of the defect was 89.45 cm2 for cases in whom local flaps were applied, 193 cm2
      for free flaps and 143 cm2 for one case treated with distant flap. Four cases
      required craniectomies because of the delay in reporting to our burns unit. Early
      surgical attempt to cover the defect with a well-vascularized tissue provides
      excellent healing, osteogenesis, short hospital staying, low rate of infection
      and requires no surgical debridement of the bone in the early phase.

PMID- 16448766
TI  - Non-accidental burns in children--are we neglecting neglect?
AB  - Although many studies have described burn abuse in detail, burns that have
      occurred as a result of neglect have been studied to a much lesser degree. A
      retrospective study of 440 hospitalised paediatric burns patients during 2000
      2002 inclusive was performed. A multidisciplinary team investigation of
      suspicious cases was used. This included a home assessment. There were 41 cases
      of neglect (9.3%) and 395 cases of accidental burning (89.8%). Parental drug
      abuse, single parent families, delay to presentation and a lack of first aid were
      statistically more prevalent in the "neglect" group than in the "accidental"
      group. Children in the "neglect" group were also statistically more likely to
      have deeper burns and require skin grafting. 82.9% of children whose burns were
      deemed to be due to neglect had a previous entry on the child protection
      register. 48.8% were transferred into foster care. This study shows that burning
      by neglect is far more prevalent than abuse. We advocate a multidisciplinary
      investigation coupled with the use of home assessments to aid diagnosis. It may
      be possible to target preventative strategies on the children with the above risk
      factors.

PMID- 16448767
TI  - Internalizing problem behavior and family environment of children with burns: a
      Dutch pilot study.
AB  - The psychosocial development of children with burns is at risk. Children with
      health care issues tend to develop internalizing problems. Several areas of
      protective or risk factors were composed into a conceptual model on how
      internalizing problems might develop or might be prevented after getting burned.
      The purpose of this study was to explore the relation between post burn
      internalizing problems on the one hand and child characteristics, burn
      characteristics and the family environment on the other hand. Data have been
      collected from 28 mothers and 27 fathers of children with burns (N=29) in six
      burn centers in The Netherlands and Belgium. The age of the participating
      children ranged from 2 to 14, TBSA ranged from 1 to 42%. Parents reported problem
      behavior on the child behavior checklist (CBCL). Three scales of the family
      environment scale (FES) have been used to explore family conflict, family
      cohesion and family control. Relations between a clinical level of internalizing
      problems, reported in 25% of the sample and the family environment were found.

PMID- 16448768
TI  - Comparison of the rates of elongation provided by multiple smaller rhomboid flaps
      and larger single rhomboid flap--an experimental study.
AB  - BACKGROUND: The rhomboid flap is one of the geometric relaxation techniques used
      for releasing burn scar contractures. PURPOSE: In the present study, we evaluated
      the question; 'which is better: one larger rhomboid flap or a series of multiple
      smaller rhomboid flaps?' METHODS: Ten male Wistar rats each weighing 250-300 g
      were used. In the groups, 2.5 cm of the inguinal region was used. Two 1 cm long
      rhomboid flaps with spaced by 0.5 cm were used in the right side and a single 2.5
      cm long rhomboid flap was used in the left side. CONCLUSION: An elongation by
      using single larger rhomboid flap (66%) is significantly bigger than an
      elongation by using multiple smaller rhomboid flaps (26%) (p<0.01).

PMID- 16448769
TI  - Infection in acute burn wounds following the Bali bombings: a comparative
      prospective audit.
AB  - INTRODUCTION: Bacterial colonisation and invasive bacterial infection remain the
      major causes of mortality and morbidity following severe burn thus ongoing
      surveillance of patients and monitoring of infection facilitates early
      intervention to minimise the risk of sepsis. The circumstances of the Bali
      bombings in October 2002, provided an opportunity to analyse the ramifications of
      lengthy transfer times, delayed resuscitation and topical treatment, on the
      primary incidence of burn wound infection (BWI). METHOD: This prospective
      clinical audit investigated the primary incidence of BWI between the usual burn
      patients admitted to the Burn Unit at Royal Perth Hospital, Western Australia,
      and a number of survivors from the Bali bombings during a 3-month audit period in
      2002. BWI was identified using the Peck et al. proposed definitions for the
      surveillance of burn wound infections. These include impetigo, surgical wound
      related infection, cellulitis and invasive infection of unexcised wounds.
      RESULTS: The incidence of primary BWI in the Bali-tourist group (68.2%) compared
      with the standard WA group (18.2%) was significant (p=0.001). CONCLUSION:
      Sensitive assessment criteria allowed for early identification of wound
      infection. A clinically significant difference in the Bali-tourist group is
      probably related to the circumstances of their injury.

PMID- 16448771
TI  - Quality of life and return to work following electrical burns.
AB  - To investigate the psychosocial outcomes following electrical burns, a cross
      sectional survey of electrical burn patients was done using three outcome tools:
      the Burn Specific Health Scale brief version (BSHS-B), the Coping with Burns
      Questionnaire (CBQ), and the Pain Patient Profile (P3). Questionnaires were
      mailed to electrical burn patients discharged from an adult regional burn centre,
      and also distributed to attendants of an electrical utility conference in
      Toronto. Twenty-six of 88 patients who were discharged from the regional burn
      centre during the study period with updated residential information were
      contacted and 14 (54%) completed the questionnaires. Twenty questionnaires were
      also distributed at the conference and 8 (40%) were completed; leaving a total of
      22 (48%) patients for the study. The average patient age was 44.0+/-11.7 years;
      21 (96%) were men, and the average time from injury to survey completion was
      5.3+/-4.9 years. Five (23%) of the 22 patients returned to the same work duties,
      10 (45%) changed duties, and 7 (32%) did not return to work. BSHS-B scores were
      low for all patients. Participants with high voltage burns (>1000 V) had worse
      sexuality scores (p<0.05), while those with larger burns (>10% TBSA) had worse
      physical scores (p<0.05). Patients surveyed >5 years from injury showed
      improvement in physical scores. CBQ scores indicated that optimism was the most
      commonly used coping strategy. P3 showed significant levels of emotional distress
      in all patients, with anxiety being more common in high voltage injuries
      (p<0.05). The data suggests that electrical burn patients may have a limited
      ability to return to work and an overall poor quality of life. Emotional distress
      is the dominant feature influencing long-term outcome in these patients. Further
      studies are warranted to validate these findings.

PMID- 16448770
TI  - Are paediatric burns more common in asylum seekers? An analysis of paediatric
      burn admissions.
AB  - The number of asylum seekers in Ireland has increased dramatically over the last
      10 years. Based on our impression that the number of children admitted to our
      burn unit was disproportionately represented by children of asylum seekers we
      performed an audit to establish (1) what proportion of admissions are from this
      subgroup and (2) the characteristics of their burns. All paediatric burn
      admissions from May 2003 to April 2004 were reviewed. Data collected from a
      retrospective chart review included patient demographics and details of the burn
      injuries. The National Census of 2002 and the Office of the Refugee Applications
      Commissioner were consulted for population statistics. Total burn admissions for
      the period were 126: Irish nationals (n=107), non-national residents (n=2),
      asylum seekers (n=14) and patients of unknown asylum status (n=3, excluded from
      study). In the asylum seeker group, the median age was 18.6 months (range 10
      months-5.3 years) with the majority less than 2 years (n=11). All burns occurred
      in the domestic setting. Scalds accounted for 13 cases, one contact burn occurred
      from a hot grill. The median total body surface area burned was 5.7% (range 1.5
      26%). The National Census of 2002 recorded a population of 3,917,203. With less
      than 12,000 asylum seekers in the country, they comprise only approximately 0.3%
      of the population yet they account for 11.4% of the burn patients admitted to our
      unit, p<0.0001. Children of asylum seekers are over-represented in our series of
      paediatric admissions for burns and are more likely than Irish children to
      sustain a burn at a younger age and in the domestic setting. This may indicate an
      increased risk of injury and warrants further investigation.

PMID- 16448773
TI  - Psychosocial outcomes derived from an acid burned population in Bangladesh, and
      comparison with Western norms.
AB  - Assault by acid burns typically results in severe disfigurement, yet the
      psychosocial impact of this injury is so far unreported. This study provides the
      first empirical data using standardised assessment scales, from 44 acid burns
      survivors in Bangladesh. Compared with published norms, individuals show high
      levels of psychological distress including social anxiety and avoidance, anxiety
      and depression. Consistent with the published literature, there is no
      relationship between severity of injury and level of psychological distress. One
      interesting feature of this population is the relative preservation of perceived
      self-concept, and this is discussed with relation to the supportive and
      therapeutic environment of the clinic where this group were studied. We also note
      an interesting sub-group who were attacked by members of their own family and for
      whom psychological morbidity seems particularly pronounced.

PMID- 16448772
TI  - Punctate scarring from use of porous Biobrane.

PMID- 16448774
TI  - Hand surface area--do racial differences exist?
AB  - The patient's own palm is used as a template in assessing small patchy burns and
      is traditionally believed to be 1% of body surface area. This does alter with the
      patient's age, sex and BMI and there have been suggestions that it can also
      differ between ethnic groups. We undertook this study to see if there were any
      differences in the hand surface area between Caucasians, Orientals and Asians. It
      was done by tracing the hand outline and calculating the surface area. The study
      showed that there was no significant difference between the three ethnic groups
      in terms of hand surface area.

PMID- 16448775
TI  - The neuropeptide tyrosine Y1R is expressed in interneurons and projection neurons
      in the dorsal horn and area X of the rat spinal cord.
AB  - The localization of the neuropeptide tyrosine Y1 receptor was studied with
      immunohistochemistry in parasagittal and transverse, free-floating sections of
      the rat lumbar spinal cord. At least seven distinct Y1 receptor-positive
      populations could tentatively be recognized: Type 1) abundant small, fusiform Y1
      receptor-positive neurons in laminae I-II, producing a profuse neuropil; Type 2)
      Y1 receptor-positive projection neurons in lamina I; Type 3) small Y1 receptor
      positive neurons in lamina III, similar to Type 1 neurons, but less densely
      packed; Type 4) a number of large, multipolar Y1 receptor-positive neurons in the
      border area between laminae III-IV, with dendrites projecting toward laminae I
      II; Type 5) a considerable number of large, multipolar Y1 receptor-positive
      neurons in laminae V-VI; Type 6) many large Y1 receptor-positive neurons around
      the central canal (area X); and Type 7) a small number of large Y1 receptor
      positive neurons in the medial aspect of the ventral horns (lamina VIII). Many of
      the neurons present in laminae V-VI and area X produce craniocaudal processes
      extending for several hundred micrometers. Retrograde tracing using cholera toxin
      B subunit injected at the 9th thoracic spinal cord level shows that several Type
      5 neurons in laminae V-VI, and at least a few Type 2 in lamina I and Type 6 in
      area X have projections extending to the lower segments of the thoracic spinal
      cord (and perhaps to supraspinal levels). The present results define distinct
      subpopulations of neuropeptide tyrosine-sensitive neurons, localized in
      superficial and deep layers of the dorsal, in the ventral horns and in area X.
      The lamina II neurons express somatostatin [The neuropeptide Y Y1 receptor is a
      somatic receptor on dorsal root ganglion neurons and a postsynaptic receptor on
      somatostatin dorsal horn neurons. Eur J Neurosci 11:2211-2225] and are presumably
      glutamatergic [Todd AJ, Hughes DI, Polgar E, Nagy GG, Mackie M, Ottersen OP,
      Maxwell DJ (2003) The expression of vesicular glutamate transporters VGLUT1 and
      VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with
      emphasis on the dorsal horn. Eur J Neurosci 17:13-27], that is they are
      excitatory interneurons under a Y1 receptor-mediated inhibitory influence. The
      remaining Y1 receptor-positive spinal neurons need to be phenotyped, for example
      if the large Y1 receptor-positive laminae III-IV neurons (Type 5) are identical
      to the neurokinin (NK)1R-positive neurons previously shown to receive
      neuropeptide tyrosine positive dendritic contacts [Polgar E, Shehab SA, Watt C,
      Todd AJ (1999) GABAergic neurons that contain neuropeptide Y selectively target
      cells with the NK1 receptor in laminae III and IV of the rat spinal cord. J
      Neurosci 19:2637-2646]. If so, neuropeptide tyrosine could have an
      antinociceptive action not only via Y1 receptor-positive interneurons (Type 1)
      but also projection neurons. The present results show neuropeptide tyrosine
      sensitive neuron populations virtually in all parts of the lumbar spinal cord,
      suggesting a role for neuropeptide tyrosine signaling in many spinal functions,
      including pain.

PMID- 16448776
TI  - Birth insults involving hypoxia produce long-term increases in hippocampal
      [125I]insulin-like growth factor-I and -II receptor binding in the rat.
AB  - Insulin-like growth factors-I and -II and insulin are structurally related
      mitogenic growth factors with multiple actions in the developing nervous system
      and adult CNS. Previous studies have demonstrated acute induction of insulin-like
      growth factors and their receptors, over a time course of several days, in
      response to hypoxic/ischemic insult to developing or adult brain. The current
      study tested whether birth insults involving hypoxia may produce long term
      changes in brain insulin-like growth factor or insulin receptor levels, lasting
      into adulthood. For this, rats were born vaginally (controls), by cesarean
      section, or by cesarean section with 15 min of added global anoxia (cesarean
      section+anoxia), and brain [125I]insulin-like growth factor-I, [125I]insulin-like
      growth factor-II and [125I]insulin receptor binding sites were assessed
      autoradiographically at adulthood. [125I]Insulin-like growth factor-I receptor
      binding sites were increased in all hippocampal subfields (CA1-CA3, dentate
      gyrus) in rats born either by cesarean section or by cesarean section+anoxia,
      compared with vaginal birth. [125I]Insulin-like growth factor-II binding was
      increased in all hippocampal subfields only in rats born by cesarean
      section+anoxia compared with either vaginal birth or cesarean section groups.
      [125I]Insulin-like growth factor-I and [125I]insulin-like growth factor-II
      binding in frontal cortex, striatum and cerebellum were unaffected by birth
      group, except for increased [125I]insulin-like growth factor-I binding in the
      cerebellar molecular layer of cesarean-sectioned animals. Birth group had no
      significant effect on [125I]insulin binding in any brain region. Affinity cross
      linking experiments performed with hippocampal membranes from the three birth
      groups showed that i) [125I]insulin-like growth factor-I and [125I]insulin-like
      growth factor-II recognized bands of molecular weights characteristic of insulin
      like growth factor-I and insulin-like growth factor-II receptors, respectively,
      and ii) [125I]insulin-like growth factor-I and [125I]insulin-like growth factor
      II were displaced more potently by their respective unlabeled ligands than by
      related molecules. It is concluded that birth insults involving hypoxia can
      induce lasting increases in insulin-like growth factor-I and -II receptors in the
      CNS. There is specificity with respect to the subtype of insulin-like growth
      factor receptor affected by the particular birth insult and the brain region
      affected. It is suggested that enduring increases in levels of insulin-like
      growth factor receptors consequent to hypoxic birth insult may help to maintain
      hippocampal function at adulthood, and could modulate responsiveness to insulin
      like growth factor administration.

PMID- 16448777
TI  - How to extend the elbow with a weak or paralyzed triceps: control of arm
      kinematics for aiming in C6-C7 quadriplegic patients.
AB  - This study aims to investigate how quadriplegic patients with a C6-C7 spinal
      lesion coordinate their upper limb to extend the elbow despite the paralysis or
      weakness of the triceps brachii, and what is the effect of a surgical
      musculotendinous transfer. For this purpose, aiming movements in a wide workspace
      were recorded in seven healthy subjects and in patients with incomplete (five
      cases) or complete (eight cases) triceps paralysis and after musculotendinous
      transfer (eight cases). We used four electromagnetic field sensors to quantify
      hand trajectory and to compute the angles describing the rotations at the
      scapula, glenohumeral joint, elbow and wrist (10 degrees of freedom). Extent and
      smoothness of the hand trajectories and hand velocity profiles were surprisingly
      similar between healthy subjects and quadriplegic patients. The reduction of
      elbow extension observed in patients was compensated by rotations distributed
      across several degrees of freedom including the scapula. Principal components
      analysis showed that the joint rotations could be summarized by an additive
      combination of two synergies, respectively orientating and stretching out the
      limb, which explained similar amounts of variance in healthy subjects and in
      patients. The participations of degrees of freedom in the synergies were roughly
      similar in the different groups of subjects, the main difference concerning
      scapular medial-lateral rotation, which seems to be critical in patients with a
      complete triceps paralysis. This demonstrates that elbow extension in
      quadriplegic patients is due to anticipated mechanical interaction coupling
      between upper limb segments. We propose that the persisting (incomplete
      paralysis) or restored (musculotendinous transfer) elbow extensor strength may
      act by stabilizing the elbow. This counterintuitive preservation of limb
      kinematics for horizontal aiming movements in quadriplegic patients despite the
      drastic changes in muscle action provoked by paralysis and/or by surgery strongly
      suggests that the motor system does not primarily control forces but the
      morphological aspects of movement, via joint rotation synergies.

PMID- 16448778
TI  - Insulin-like growth factor I and II expression and modulation in amoeboid
      microglial cells by lipopolysaccharide and retinoic acid.
AB  - Insulin-like growth factors I and II are known to regulate the development of the
      CNS. We examined the developmental changes in insulin-like growth factor I and
      insulin-like growth factor II expression in the postnatal rat corpus callosum.
      Insulin-like growth factor I and insulin-like growth factor II mRNA expression
      increased at 3 days as compared with 1 day whereas the protein expression
      increased up to 7 days. Insulin-like growth factor I and insulin-like growth
      factor II immunoexpression was specifically localized in round cells confirmed by
      double immunofluorescence with OX-42 to be the amoeboid microglial cells. Insulin
      like growth factor I expression was observed up to 7 days in amoeboid microglial
      cells while insulin-like growth factor II expression was detected in 1-3 day old
      rats. Exposure of primary rat microglial cell cultures to lipopolysaccharide
      increased insulin-like growth factor I and insulin-like growth factor II mRNA and
      protein expression significantly along with their immunoexpression in microglial
      cells. The lipopolysaccharide-induced increase in insulin-like growth factor I
      and insulin-like growth factor II mRNA and protein expression was significantly
      decreased with all-trans-retinoic acid. We conclude that insulin-like growth
      factor I and insulin-like growth factor II expression in amoeboid microglial
      cells in the developing brain is related to their activation. Once the activation
      is inhibited, either by transformation of the amoeboid microglial cells into
      ramified microglia regarded as resting cells or as shown by the effect of all
      trans-retinoic acid administration, insulin-like growth factor I and insulin-like
      growth factor II mRNA and protein expression is downregulated.

PMID- 16448779
TI  - Sympathetic genital responses induced by p-chloroamphetamine in anaesthetized
      female rats.
AB  - In urethane-anesthetized female rats, a branch of the hypogastric nerve
      equivalent to the vas deferens nerve in males was shown anatomically and
      electrophysiologically to supply the uterine horns and we have consequently
      termed this the uterine nerve. Administration of p-chloroamphetamine i.v.
      elicited patterned bursting uterine nerve activity responses together with
      contractions of the uterine horns and musculature of the vaginal wall. These
      responses are qualitatively similar to ejaculatory responses observed following p
      chloroamphetamine administration to anesthetized male rats and the urethrogenital
      reflex in females, suggesting they represent responses occurring during sexual
      processes. This response to p-chloroamphetamine was still present after complete
      transection of the spinal cord at T8. These data indicate that common
      neurophysiological and pharmacological mechanisms regulate genital reflexes at
      the lumbosacral spinal level in both the female and the male rat.

PMID- 16448780
TI  - Associations between disordered eating behaviors and licit and illicit substance
      use and abuse in a university sample.
AB  - OBJECTIVES: To examine associations between discrete eating disordered behaviors
      as well as clusters of eating disordered behaviors in relation to the use and
      abuse of a wide spectrum of substance classes, both licit and illicit, in a
      female university sample. METHODS: Women with particular types of eating
      disordered behaviors were selected from a pool of 526 students who completed the
      Women's Health Survey. Analyses compared the frequencies of lifetime engagement
      in a wide range of licit and illicit substances between each of the eating
      disorder groups and the normal control group. RESULTS: Associations were found
      between severe levels of alcohol consumption and binge eating, dieting with
      purging and the use of central nervous stimulants, and bingeing with dieting and
      tobacco use and the abuse of prescription medications. CONCLUSION: Examining a
      broad range of substance classes, with differing physiological properties and
      effects, in relation to specific disordered eating behaviors, could contribute to
      theory development regarding the functions of the specific co-occurring
      behaviors.

PMID- 16448781
TI  - Maternal smoking during late pregnancy and offspring smoking behaviour.
AB  - We explored the influence of maternal smoking during late pregnancy on the
      likelihood of smoking among offspring in adolescence and adulthood, using birth
      cohort data collected in the United Kingdom as part of the 1958 National Child
      Development Study. Longitudinal analysis indicated that maternal smoking during
      late pregnancy was associated with an increased likelihood of being a non-smoker
      at 16-year, 23-year and 33-year follow-up. This association differed between male
      and female offspring, with women showing no significant association and men
      showing an increased likelihood of being a non-smoker. There did not appear to be
      any association between maternal smoking during late pregnancy and cigarette
      consumption among offspring who reported smoking for either sex. These results
      are inconsistent with some previous reports that maternal smoking during
      pregnancy increases the likelihood of smoking among female offspring, although
      the observation of a moderating effect of sex on smoking behaviour is consistent
      with several previous reports. We discuss possible mechanisms for this
      association, and suggest factors that may account for the observed sex
      differences in this association, and the discrepancy between our results and some
      previous reports.

PMID- 16448782
TI  - Predictors of the participation of smoking parents in a proactive telephone-based
      smoking cessation program.
AB  - OBJECTIVE: The objective of this study is to identify the predictors of
      participation by smoking parents in a proactive telephone-based smoking cessation
      program. METHODS: The smoking parents of young children from a birth cohort were
      interviewed and invited to take part in a telephone-based smoking cessation
      program. The characteristics of the parents and the predictors of participation
      were analyzed by chi-square test and by logistic regression. RESULTS: A total of
      952 (82.9%) out of the 1149 smoking parents who were interviewed agreed to
      participate in the smoking cessation program. The analysis showed that the
      predictors of participation in a pro-active smoking cessation program are being
      from a middle-income household, being currently employed, having recently had a
      medical consultation or been hospitalized, being at the stage of contemplating a
      change in behavior, and perceiving the importance of quitting smoking.
      CONCLUSIONS: Recruitment approaches should be refined according to the identified
      factors to target those who might decline an invitation to participate in a
      smoking cessation program.

PMID- 16448783
TI  - The Fagerstrom Test for Nicotine Dependence-Smokeless Tobacco (FTND-ST).
AB  - Few nicotine dependence measures have been developed for smokeless tobacco (ST)
      users. Existing measures are limited by the requirement to rate the nicotine
      content of ST brands for which data is scarce or non-existent. We modified the
      Fagerstrom Test for Nicotine Dependence (FTND) for ST users, referred to this
      scale as the FTND-ST, and evaluated its characteristics in a population of 42 ST
      users. The correlation between the FTND-ST total score and the serum cotinine
      concentrations was 0.53 (p<0.001). Internal consistency reliability assessed
      using the coefficient alpha was 0.47. Correlations and the coefficient alpha are
      similar to those reported for commonly used nicotine dependence measures.
      Development and refinement of nicotine dependence measures for ST users are
      essential steps in order to advance the field of ST research.

PMID- 16448784
TI  - Rembrandt's Bathsheba, possible lactation mastitis following unsuccessful
      pregnancy.
AB  - Deformity of the left breast and axilla observed in Rembrandt's famous painting
      "Bathsheba at her toilet" (1654, Louvre Paris) has been discussed by several
      researchers. Proposed diagnoses were breast cancer and abscess due to
      tuberculosis. The present article reviews previous articles written concerning
      the left breast abnormalities of Bathsheba and carefully examines other works of
      Rembrandt modeled by Hendrickje and painted around 1654. Previous diagnosis of
      breast cancer and tuberculous mastitis is less probable. Because Hendrickje
      survived for more then 9 years after the painting and in other works modeled by
      Hendrickje shows no signs of cachexia or permanent changes in the left breast.
      The most likely diagnosis of the left breast deformity of Bathsheba is a sequela
      of lactation mastitis abscess following miscarriage or premature childbirth
      without breast feeding.

PMID- 16448785
TI  - Adrenocortical adenoma with rhabdoid features.
AB  - We report a case of an aldosterone producing adrenocortical adenoma with rhabdoid
      features in a 16-year-old girl. Grossly, the tumor measured 30 mm in diameter and
      weighed 24 g. Histologically, the tumor was composed of approximately equal parts
      of tumor cells with rhabdoid features arranged in a solid and trabecular pattern
      and cells characterized by compact eosinophilic cytoplasm, solid growth with
      focal necroses, and increased mitotic activity. The lipid-rich tumor cells with
      ample clear vacuolized cytoplasm represent a minor component.
      Immunohistochemically, all the tumor cells showed the same results and were
      positive for vimentin, synaptophysin, Melan A, and alpha-inhibin. Cytokeratin CAM
      5.2 was positive only focally. Chromogranin A, actin, alpha-actin, S100 protein,
      EMA, and cytokeratin AE1/AE3 were negative. Rhabdoid features have been described
      in many tumors of variable histogenesis; however, to the best of our knowledge,
      the presence of rhabdoid phenotype has never been described in either
      adrenocortical adenoma or carcinoma.

PMID- 16448786
TI  - Mutational analysis of the kinase domain of MYLK2 gene in common human cancers.
AB  - Genetic alterations of the genes encoding protein kinases have been implicated in
      the development of human cancers. Myosin light chain kinase 2, skeletal muscle
      (MYLK2) encodes a calcium/calmodulin-dependent serine/threonine kinase. In a
      recent study, MYLK2 gene was somatically mutated in colorectal carcinomas. The
      aim of this study was to explore the possibility that other common human
      carcinomas besides colorectal carcinomas harbored MYLK2 mutations in the kinase
      domain. We analyzed exons 6 and 7 eccoding the kinase domain of MYLK2 for somatic
      mutations in 60 gastric, 104 colorectal, 79 non-small cell lung, and 54 breast
      cancers using a polymerase chain reaction (PCR)-based single-strand conformation
      polymorphism (SSCP). We found one MYLK2 mutation in lung adenocarcinomas, but not
      in other cancers. The MYLK2 mutation detected was a missense mutation that would
      substitute an amino acid (E374D) However, there was no somatic mutation of the
      MYLK2 gene. These data suggest that the kinase domain of MYLK2 is rarely mutated
      in common human carcinomas and that it does not play a dominant role in cancer
      pathogenesis.

PMID- 16448787
TI  - The complete mitochondrial genome of the orbiniid polychaete Orbinia latreillii
      (Annelida, Orbiniidae)--A novel gene order for Annelida and implications for
      annelid phylogeny.
AB  - Relationships of annelid subtaxa are controversially discussed and additional
      markers are necessarily needed to get further insights into their evolution. Due
      to their high content of information, mitochondrial genomes have been proven very
      useful in phylogenetic analyses. Whereas many complete mitochondrial genomes of
      arthropods are available, lophotrochozoan taxa are only scarcely represented and
      this is especially true for annelids. Here we present the complete mitochondrial
      genome of the orbiniid polychaete Orbinia latreillii. The circular genome is
      15,558 bp in size and contains the same 37 genes as found in most other
      metazoans. As in the case for all studied annelids all genes are transcribed from
      the same strand. Compared with the known data from other annelids at least five
      gene translocations must be hypothesized for O. latreillii. A comparison of the
      available data shows that gene translocations within Annelida seem to be less
      frequent than in molluscs, but more frequent as previously assumed. Phylogenetic
      analyses of mitochondrial DNA sequence data and amino acid data support an
      inclusion of Sipuncula within Annelida and a closer relationship to orbiniids is
      recovered for this taxon.

PMID- 16448788
TI  - Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate
      5-kinase, PIKfyve/Fab1.
AB  - Yeast Fab1 is a phosphatidylinositol 3-phosphate 5-kinase involved in endocytic
      membrane traffic and vacuole homeostasis. Here we have cloned and sequenced the
      cDNA for the human homologue of Fab1, PIKfyve. The cDNA has an open reading frame
      of 6294 bp and encodes a 2098-amino acid protein with a calculated molecular mass
      of 237 kDa, containing a phosphatidylinositol 3-phosphate-binding FYVE domain, a
      DEP domain, a chaperonin-like domain, and a phosphoinositide kinase domain. The
      human genome contains a single PIKfyve gene, which comprises 38 exons on
      chromosomal locus 2q34. PIKfyve is expressed as a single molecular species in a
      number of human cell lines derived from different tissues. The exogenously
      expressed protein was found to localize mainly to early endosomes containing two
      other FYVE domain proteins, EEA1 and Hrs. The endosomal membrane localization of
      PIKfyve was studied in more detail by examining cells transfected with a
      constitutively active mutant of the small GTPase Rab5, whose expression results
      in the enlargement of early endosomes. We show that PIKfyve is distributed in
      microdomains that are distinct from those occupied by EEA1 and Hrs.

PMID- 16448789
TI  - External quality assurance system for antibiotic resistance in bacteria of animal
      origin in Europe (ARBAO-II), 2003.
AB  - Initiated in 2003 by the European Union, ARBAO-II aims to establish a monitoring
      of antimicrobial susceptibility among the veterinary laboratories in all European
      countries based on validated methodologies. This includes an external quality
      control system for the most important bacterial pathogens. In 2003 two trials
      were performed. The first on Salmonella and Escherichia coli involved 31
      laboratories in 18 countries and the second on Staphylococcus and Streptococcus
      included 22 laboratories in 15 countries. For the E. coli strains, 92.8% of the
      results complied with the reference MICs, for Salmonella 93.7%, for Streptococcus
      80.4% and for Staphylococcus 93.1%. Most problems were observed when testing
      florfenicol (79.2% correct), gentamicin (84.2%) and amoxicillin + cl (84.9%) in
      E. coli; streptomycin in Salmonella (62.5%); gentamicin (56.7%), lincomycin
      (71.4%), clindamycin (75.4%), TMP + sulfonamides (75.7%) and chloramphenicol
      (78.5%) in Streptococcus; erythromycin (81.5%) and oxacillin (78.2.5%) in
      Staphylococcus. A few laboratories caused most deviations. However, there was no
      correlation between good performance for one bacterial group and good performance
      for other groups. This study showed that most laboratories are capable of
      performing correct susceptibility testing for E. coli and Salmonella, even though
      performance of some laboratories can be improved, and that some problems exist
      for Staphylococcus and Streptococcus. This clearly shows the need for continuous
      harmonisation of methodologies within the EU.

PMID- 16448791
TI  - Relationship of cloacal gland with testes, testosterone and fertility in
      different lines of male Japanese quail.
AB  - An attempt has been made to investigate the relationship of cloacal gland with
      testes, testosterone and fertility in different lines of Japanese quail (Coturnix
      coturnix japonica). For this study, three lines of healthy adult male Japanese
      quails (<12 weeks) viz., heavy body weight (HB), white breasted (WB), and white
      egg shell (WES) were taken. They were housed in individual cages under uniform
      husbandry conditions and were provided with normal quail breeder ration and water
      ad libitum, with 14 h light/day. The experimental birds were selected from each
      of these three lines and categorized into different groups (15 birds/group) based
      on the increasing order of the area of cloacal gland. At the end of this
      experiment (24 weeks) the data indicated that size of the cloacal gland was
      directly proportional to foam discharge, foam weight, testicular weight,
      fertility and testosterone concentration in plasma. From this study it may be
      concluded that area of cloacal gland in Japanese quail is positively correlated
      with testicular weight, level of testosterone in plasma and fertility. Visual
      examination of cloacal gland and cloacal foam may provide a valuable non-invasive
      tool for predicting the fertilizing ability of individual male bird.

PMID- 16448790
TI  - Antagonism of TCDD-induced ethoxyresorufin-O-deethylation activity by
      polybrominated diphenyl ethers (PBDEs) in primary cynomolgus monkey (Macaca
      fascicularis) hepatocytes.
AB  - Polybrominated diphenyl ethers (PBDEs) are widespread environmental pollutants,
      and the levels of certain congeners have been increasing in biota and abiota in
      recent decades. Some PBDEs are lipophilic and persistent, resulting in
      bioaccumulation in the environment. Their structural similarity to other
      polyhalogenated aromatic hydrocarbons (PHAHs) such as polychlorinated biphenyls
      (PCBs) has raised concerns that PBDEs might act as agonists for the aryl
      hydrocarbon receptor (AhR). Recent studies in our laboratory with human and rat
      cell lines indicated no AhR mediated CYP1A1 induction for PBDEs. However, an
      earlier in vitro study by Van der Burght et al. (1999) [Van der Burght, A.S.,
      Clijsters, P.J., Horbach, G.J., Andersson, P.L., Tysklind, M., van den Berg, M.,
      1999. Structure-dependent induction of CYP1A by polychlorinated biphenyls in
      hepatocytes of cynomolgus monkeys (Macaca fascicularis). Toxicol. Appl.
      Pharmacol. 155, 13-23] indicated that in cynomolgus monkey (M. fascicularis)
      hepatocytes PCBs with a non-planar configuration could induce CYP1A. As PBDEs
      show a structural similarity with non-planar (ortho substituted) PCBs, our
      present study focused on the possible CYP1A induction by PBDEs (BDE-47, -99, 
      100, -153, -154, -183, and -77) in individual preparations (n=4) of primary
      hepatocytes of cynomolgus monkeys (M. fascicularis). 7-Ethoxyresorufin-O
      deethylase (EROD) was used as a marker for CYP1A-mediated catalytic activity.
      Cells were exposed for 48 h to various PBDE concentrations (0.01-10 microM),
      positive controls 2,3,7,8-TCDD (0.001-2.5 nM) and PCB-126 (0.01-10nM), and
      negative control (DMSO vehicle alone). No statistically significant induction of
      CYP1A was observed in the hepatocytes after 48 h of exposure to all
      environmentally relevant PBDEs. After exposing hepatocytes to PBDEs in
      combination with TCDD, a concentration-dependent decrease in TCDD-induced EROD
      activity was observed. All PBDEs tested showed a similar reduction in each of
      four experiments, though quantitative differences were observed. The observed
      antagonism of TCDD-induced EROD activity by PBDEs occurred in both male (n=3) and
      female (n=1) hepatocytes and was not due to catalytic inhibition of EROD activity
      or cytotoxicity. However, based on the results of this study we do not expect
      these antagonistic effects of PBDEs on CYP1A induction at environmental relevant
      levels, since these in vitro interactive effects with TCDD were observed only at
      relatively high concentrations that are normally not seen, e.g. in the human
      body.

PMID- 16448792
TI  - Storage of bovine isolated follicles: a new alternative way to improve the
      recovery rate of viable embryos from ovarian follicles of slaughtered cows.
AB  - The vitality of bovine oocytes stored in isolated follicles was examined. The aim
      of this work was to prolong the time of in vitro manipulation of oocytes before
      their maturation and develop a new alternative of oocyte "capacitation" to
      improve the quality of in vitro produced embryos. Follicles were dissected from
      the ovaries of slaughtered cows; subsequently, follicles were divided according
      to their diameter into three categories (2-3, 3-4 and 4-6 mm), and stored at 17
      18 degrees C for 24 or 48 h in a modified tissue culture medium-199 (TCM-199)
      with reduced pH. After that time, the cumulus-oocyte complexes (COCs) were
      isolated, matured, fertilized, and embryos cultured in vitro for a total of 9
      days. The percentage of total blastocysts, and hatched blastocysts developed from
      oocytes, initially kept ("capacitated") for 24h at 17-18 degrees C, within
      follicles of 3-6mm size categories, were significantly higher than that oocytes
      of the control [of control oocytes] (44.9 and 30.3% versus 36.2 and 20.4%,
      respectively). The oocytes of follicles stored for 48 h at 17-18 degrees C
      already had decreased developmental capacity. Interesting data were obtained when
      COCs of the 3-4 and 4-6 categories were additionally divided into two subgroups
      according to their presumed developmental history (originating from the supposed
      growing "fit" in contrast to the supposed regressing "unfit" follicles). The
      higher improvement in the rate of hatched blastocysts from 24h stored oocytes was
      observed only in the subgroup originated from "fit" COCs (15.3 versus 25.0%, and
      20.0 versus 34.4%, in the 3-4 and 4-6mm categories, respectively). The transfer
      of 26 blastocysts (developed of follicles kept for 24h at 17-18 degrees C) to 26
      recipient heifers resulted in 18 pregnancies. Storage of follicles at 17-18
      degrees C in vitro resulted not only in recovery of higher numbers of blastocysts
      of better quality but also facilitated the safe transport of follicles for a long
      distance. The extended, time of follicle storage before the proper oocyte
      maturation allowed also the synchronization of an appropriate number of recipient
      animals according to the number of isolated follicles.

PMID- 16448793
TI  - Phytochemical screening and effect of aqueous extract of Ficus sycomorus L.
      (Moraceae) stem bark on muscular activity in laboratory animals.
AB  - The stembark of Ficus sycomorus was collected, dried and extracted to screen for
      some chemical constituents and study its effect on muscle contraction. The
      duodena and recti abdominis of 10 guinea pigs weighing between 330 and 34 g and
      10 frogs weighing between 180 and 201 g, respectively were isolated and used for
      this study. The extract was tested to see its effect on acetylcholine-induced
      contraction on kymograph. The extract reduced the acetylcholine contractile
      responses of guinea pigs duodena and recti abdominis muscles of frogs
      significantly, thus showing inhibitory effect on muscle contraction. The extract
      showed the presence of gallic tannins, saponins, reducing sugars, alkaloids and
      flavone aglycones. It was concluded that the extract has inhibitory effect on
      both smooth and skeletal muscles contractions and contains important constituents
      for pharmacological activities.

PMID- 16448794
TI  - Nucleotide variability of HV-I in admixed population of the Brazilian Amazon
      Region.
AB  - The analysis of genetic variation in the nucleotide sequences of mitochondrial
      DNA has been used as a tool in the study of history of different human
      populations, as Amerindians, Afro-descendents populations and furthermore admixed
      populations. In this study, the mitochondrial DNA was analyzed in 158 unrelated
      individuals in an admixed population of the Amazonian Region: Santarem-PA-Brazil.
      The polymorphisms were detected using both levels, analysis of restriction enzyme
      and direct sequencing. We observed a total of 49 different haplotypes were found
      determined by 46 variable nucleotides. The more frequent haplotypes (Hap03) was
      shared by five samples and 43 sequences were unique. The genetic diversity was
      estimated to 0.989+/-0.0067 and the probability of two random individuals showed
      identical mitochondrial DNA (mtDNA) haplotypes were 2.8%.

PMID- 16448795
TI  - Quantitative LC-MS determination of strychnine in urine after ingestion of a
      Strychnos nux-vomica preparation and its consequences in doping control.
AB  - A simple, fast and sensitive method for the quantitative determination of
      strychnine residues in urine has been developed and validated. The method
      consists of a liquid-liquid extraction step with ethyl acetate at pH 9.2,
      followed by LC-MS/MS in positive atmospheric pressure chemical ionization (APCI)
      mode. The method is linear in the range of 1-100 ng/mL and allows for the
      determination of strychnine at sub-toxicological concentrations. The accuracy of
      the method ranged from 1.3% to 4.4%. The method was used to determine the
      excretion profile of strychnine after the ingestion of an over-the-counter herbal
      preparation of Strychnos nux-vomica. Each volunteer ingested a dose equivalent to
      380 micro g of strychnine. This dose is lower than the prescription dose but
      results in the detection of strychnine for over 24-h post administration. Maximum
      detected urinary concentrations ranged from 22.6 to 176 ng/mL. The results of
      this study show that the use of this type of preparation by athletes can lead to
      a positive doping case.

PMID- 16448796
TI  - Nucleotide variability of HV-I in Afro-descendents populations of the Brazilian
      Amazon Region.
AB  - The analysis of genetic variation in the nucleotide sequences of mitochondrial
      DNA, provides unique information about the population diversity and human
      identification. In this study, the mitochondrial DNA sequences of the first
      hypervariable region (HV-I) were analyzed in 243 unrelated individuals of seven
      Afro-descendents populations of the Amazon Region. Sequence polymorphisms were
      detected using PCR and direct sequencing analysis. A total of 133 different
      haplotypes were found determined by 97 variable nucleotides. Each one of the
      three more frequent haplotypes was shared by 9 samples and 91 sequences were
      unique. The genetic diversity was estimated to 0.9898+/-0.0016 and the
      probability of two random individuals showed identical mitochondrial DNA (mtDNA)
      haplotypes were 1.2%.

PMID- 16448797
TI  - A rapid chromogenic microtitre assay of arginine aminopeptidase activity in
      Mycoplasma strains.
AB  - Arginine-utilizing strains of Mycoplasma can be screened by assay of their
      arginine aminopeptidase activity. A standardized chromogenic method is described
      that enables enzyme detection in small volumes of cell suspension in less than 3
      h. Cell suspensions (10 microl) in 96-well microtitre plates are incubated at 37
      degrees C, pH 8.0, with 0.1 mM arginyl-beta-naphthylamide (100 microl). This is
      hydrolysed to release beta-naphthylamine, which gives a coloured product on
      diazotization with fast garnet. M. alkalescens can be detected in this way with
      as few as 1.1 x 10(5) viable cells and M. fermentans with 2.3 x 10(6) cells. The
      method has been shown to enable division of 28 strains into three groups of
      fermentative and arginine-hydrolysing mycoplasmas. This procedure has potential
      for routine laboratory use.

PMID- 16448798
TI  - Downstream processing of oncoretroviral and lentiviral gene therapy vectors.
AB  - Retroviral vectors from both oncoretroviral and lentiviral origins have a great
      potential as gene delivery vehicles. A number of research groups have devoted
      considerable effort to the development of large-scale production strategies for
      retroviral vectors. However, the manufacturing of clinical-grade vectors for gene
      therapy, especially for in vivo applications, additionally requires scaleable
      purification strategies to remove the contaminants present in the harvested
      supernatants while preserving the functionality of the vectors. In this article,
      we review recent advances made in the field of downstream processing of
      retroviral vectors. The methods currently described in the literature for
      clarification, concentration and purification of retroviral vectors will be
      presented, with special emphasis on novel chromatography methods that open up the
      possibility to selectively and efficiently purify retroviruses on a large-scale.
      Problems associated with stability and quantification of retroviral particles
      will be outlined and future challenges will be discussed.

PMID- 16448799
TI  - Comparison of effects of nursing care to problem solving training on levels of
      depressive symptoms in post partum women.
AB  - OBJECTIVE: The aim of this study was to compare the effect of nursing
      intervention to the effect of problem solving training on the level of postpartum
      depressive symptom. METHODS: We utilized a pretest-posttest mutual controlled
      semi experimental model for this study. The study consisted of 62 women (30 in
      care group and 32 in training group), all of who were at risk for postpartum
      depression, but without major depressive symptoms. These women were not
      undergoing pharmacologic or psychotherapeutic treatment, were all literate and
      consented to join the study in Erzurum, Turkey. Participants (N=62), recruited
      over a 9 month, were randomly assigned to one of two groups. Women in care group
      (average age=21, 33.3% primaparus) were given nursing care for her depressive
      symptoms. Women in training group (average age=25, 33.9% primaparus) were taught
      problem solving skills. RESULTS: Depressive symptoms were assessed before and
      after nursing interventions. We found that nursing care was effective women for
      with depressive symptoms (McNemar test, p<0.001), and problem-solving training
      was also effective (McNemar test, p<0.05). When the effectiveness of nursing care
      and the problem solving education was compared utilizing the BDI, it was found
      out that the nursing care was more effective than education alone (t=4.529,
      p<0.05). CONCLUSION: Results from this study suggest that nursing care and
      problem solving training may be use confidently in the primary care setting by
      nurses for women with postpartum depressive symptoms. PRACTICE IMPLICATION:
      Nurses play on important role in its detection and can reduce depressive
      symptoms. Public health nurses are equipped with care paths addressing specific
      health needs of depressed women in the primary care setting. Our finding indicate
      that these two programs of study can converge with meaningful results, and
      perhaps future research could address these points in a theoretical framework.

PMID- 16448800
TI  - Involvement of Salmonella enterica serovar Typhi RpoS in resistance to NO
      mediated host defense against serovar Typhi infection.
AB  - The involvement of nitric oxide (NO) in host defense and cytoprotective functions
      in murine salmonellosis has been reported. Salmonella mutants with the altered
      sigma factor RpoS (sigmaS) are less virulent and are susceptible to various
      stresses. This study investigated the role of the rpoS gene of Salmonella
      enterica serovar Typhi in NO-dependent host defense in vitro and in vivo. Wild
      type mice and mice deficient in inducible NO synthase (iNOS) were infected
      intraperitoneally or orally with serovar Typhi strains. iNOS-deficient mice were
      more susceptible to infection by both wild-type and rpoS mutant strains of
      serovar Typhi and showed extensive apoptotic liver damage compared with wild-type
      mice. Intracellular killing of Salmonella was analyzed with RAW 264 macrophage
      like cells and primary peritoneal macrophages from wild-type and iNOS-deficient
      mice after cells were infected with the serovar Typhi parent or rpoS mutant
      strain. The rpoS mutant was more susceptible to killing by macrophages than was
      the wild-type strain. Also, the wild-type strain produced more extensive
      apoptotic changes in macrophages than did rpoS mutant. These effects were
      nullified in RAW 264 cells treated with an NOS inhibitor and in iNOS-deficient
      primary macrophages. Peroxynitrite susceptibility assays of these strains were
      also performed. The rpoS mutant Typhi strain was more sensitive to in vitro
      peroxynitrite treatment than was the parent strain. Together these data show that
      NO has a significant host defense function during serovar Typhi infection, and
      that Salmonella RpoS, because it reacts to the presence of NO or its reactive
      derivatives, is thought to have a role in the pathogenicity of serovar Typhi.

PMID- 16448801
TI  - Virulence comparison in mice of distinct isolates of type A Francisella
      tularensis.
AB  - Francisella tularensis subspecies tularensis (type A F. tularensis) is considered
      to be one of the most virulent of all bacterial pathogens. Mice are extremely
      susceptible to infection with this subspecies (LD100 via various inoculation
      routes is <10 cfu). However, it has not been established whether overt virulence
      differences exist amongst type A strains of F. tularensis. To this end, the
      present study compared the virulence of two distinct type A strains, FSC033 and
      SCHU S4, for naive mice and mice immunized with the live vaccine strain of the
      pathogen, F. tularensis LVS. One nominal isolate of SCHU S4 was found to be
      completely avirulent. Another isolate was highly virulent, but all examined cases
      appeared somewhat less virulent than FSC033. The implication of these findings
      for future infection and immunity studies is discussed.

PMID- 16448802
TI  - Localization of equilibrative nucleoside transporters in the rat brain.
AB  - Adenosine is a recognized inhibitory neuromodulator and neuroprotective agent in
      the central nervous system. It is produced both intra- and extracellularly and
      transported across the cell membrane. Nucleoside transporters thus have a major
      impact on the extracellular adenosine levels, and consequently adenosine
      signalling. We have raised and characterized polyclonal antibodies against both
      the equilibrative nucleoside transporters 1 and 2, and report for the first time
      their distribution in rat brain at the cellular level. Double staining studies
      were performed to assess the localization of the transporters in neural and glial
      cells. Both transporters were present in practically all neurons. Some astrocytes
      showed equilibrative nucleoside transporter 1 staining, while equilibrative
      nucleoside transporter 2 staining on astrocytes was observed only sporadically.

PMID- 16448803
TI  - Gray matter abnormalities associated with duration of untreated psychosis.
AB  - PURPOSE: A long duration of untreated psychosis (DUP) is associated with
      relatively poor clinical and social outcomes. In order to identify whether an
      anatomically mediated mechanism may give rise to poorer outcomes, it is important
      to identify whether a long DUP is associated with greater brain structural
      abnormalities. METHOD: 81 patients with first-episode psychosis (schizophrenia,
      affective, and other psychoses) were scanned using high resolution Magnetic
      Resonance Imaging. DUP was defined as the number of days between first onset of
      psychotic symptoms and first contact with mental health services. High-resolution
      MRI images and voxel-based methods of image analysis were used to investigate
      brain structure in these patients. RESULTS: Longer DUP was associated with gray
      matter reductions in left middle and inferior temporal, left occipital and left
      fusiform cortices, and with gray matter excess of the left basal ganglia. All
      findings remained significant when co-varying for exposure to antipsychotic
      treatment. CONCLUSIONS: Temporal gray matter reductions are more marked in
      patients with a long DUP. This could reflect a progressive pathological process
      that is active prior to treatment. Alternatively, these abnormalities could be
      associated with a more insidious onset of illness and a later presentation to
      services.

PMID- 16448804
TI  - Schizophrenia patients show intact immediate error-related performance
      adjustments on an antisaccade task.
AB  - OBJECTIVE: Schizophrenia patients consistently show impairments on tasks
      requiring inhibition such as the antisaccade task. Deficits in performance
      monitoring including the detection of errors and subsequent adjustments to
      performance may contribute to such impairments. We examined whether immediate
      error-related performance adjustments during the antisaccade task were intact in
      schizophrenia. METHOD: We compared 21 schizophrenia patients and 14 healthy
      control subjects on the following measures: 1) error-related, trial-by-trial
      adjustments in reaction time (pre-error speeding, faster errors and post-error
      slowing); 2) the speed-accuracy trade-off (SATO) function; and 3) the frequency
      and type of error self-correction. RESULTS: Although antisaccade performance in
      schizophrenia was characterized by increased errors and latency of correct
      responses, measures of immediate error-related performance adjustments were
      intact. CONCLUSION: Schizophrenia is characterized by intact immediate error
      related performance adjustments, even in the context of impaired antisaccade
      performance. It is possible that deficiencies in other aspects of error
      processing, indexed by electrophysiological and hemodynamic markers, contribute
      to antisaccade and other cognitive deficits in schizophrenia.

PMID- 16448805
TI  - Anxiety and depression symptoms in psychometrically identified schizotypy.
AB  - The neurodevelopmental vulnerability for schizophrenia appears to be expressed
      across a dynamic continuum of adjustment referred to as schizotypy. This model
      suggests that nonpsychotic schizotypic individuals should exhibit mild and
      transient forms of symptoms seen in full-blown schizophrenia. Given that
      depression and anxiety are reported to be comorbid with schizophrenia, the
      present study examined the relationship of psychometrically defined schizotypy
      with symptoms of depression and anxiety in a college student sample (n=1258). A
      series of confirmatory factor analyses indicated that a three-factor solution of
      positive schizotypy, negative schizotypy, and negative affect provided the best
      solution for self-report measures of schizotypy, anxiety, and depression. As
      hypothesized, the model indicated that symptoms of depression and anxiety are
      more strongly associated with the positive-symptom dimension of schizotypy than
      with the negative-symptom dimension. This is consistent with studies of
      schizophrenic patients and longitudinal findings that positive-symptom
      schizotypes are at risk for both mood and non-mood psychotic disorders, while
      negative-symptom schizotypes appear more specifically at risk for schizophrenia
      spectrum disorders.

PMID- 16448806
TI  - Decreased volume of left and total anterior insular lobule in schizophrenia.
AB  - The insula is anatomically situated to be critically involved in many bio
      behavioral functions impaired in schizophrenia. Furthermore, its total volume has
      been shown to be reduced in schizophrenia. In the present study, we tested the
      hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl))
      rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that
      limbic system abnormalities are central in schizophrenia and that the
      affiliations of the limbic system are principally with the anterior insular
      lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to
      measure the cortical volume of the left and right anterior and posterior insular
      subdivisions. The subjects included a sample of healthy community controls (N=40)
      and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula
      volumes with positive and negative symptoms. We found that the total aINS(lbl),
      and the left aINS(lbl) in particular, were significantly volumetrically smaller
      in schizophrenia compared to controls, and significantly correlated with bizarre
      behavior. Given that the anterior insular lobule offers anatomic features that
      allow for MRI-based morphometric analysis, namely its central and circular sulci,
      this brain structure provides a useful model to test hypotheses regarding
      genotype-phenotype relationships in schizophrenia using the anterior insular
      lobule as a candidate endophenotype.

PMID- 16448808
TI  - The role of nicotinic acetylcholine receptors in Alzheimer's disease.
AB  - The two hallmark lesions of Alzheimer's disease (AD) are extracellular amyloid
      plaques, mainly formed by a small peptide called amyloid-beta (Abeta), and
      neurofibrillary tangles, which are intracellular inclusions formed by aggregates
      of hyperphosphorylated tau protein. One of the major neurochemical features of AD
      is the marked reduction of nicotinic acetylcholine receptors in disease-relevant
      brain regions such as the cerebral cortex and hippocampus. This loss is further
      compounded by the loss of cholinergic cells, which contributes to the cognitive
      dysfunction. This observation has had a major impact on therapeutic treatments,
      as efforts to restore cholinergic function such as the administration of
      acetylcholinesterase inhibitors have been, until recently, the major treatment
      options available for AD. Understanding the relationship of these hallmark
      lesions with the plethora of other changes that occur in the AD brain has proven
      to be a difficult challenge to resolve. The utilization of transgenic mouse
      models, that recapitulate one or more neuropathological and neurochemical
      features of the AD brain is providing some inroads, as they offer a means to gain
      mechanistic insights into the disease process in an in vivo setting. In this
      review, we consider the role of nicotinic acetylcholine receptors in transgenic
      models and in AD.

PMID- 16448809
TI  - Early abnormalities in transgenic mouse models of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative and fatal human
      disorder characterized by progressive loss of motor neurons. Transgenic mouse
      models of ALS are very useful to study the initial mechanisms underlying this
      neurodegenerative disease. We will focus here on the earlier abnormalities
      observed in superoxide dismutase 1 (SOD1) mutant mice. Several hypotheses have
      been advanced to explain the selective loss of motor neurons such as apoptosis,
      neurofilament disorganisation, oxidative stress, mitochondrial dysfunction,
      astrogliosis and excitotoxicity. Although disease onset appears at adulthood,
      recent studies have detected abnormalities during embryonic and postnatal
      maturation in animal models of ALS. We reported that SOD1(G85R) mutant mice
      exhibit specific delays in acquiring sensory-motor skills during the first week
      after birth. In addition, physiological measurements on in vitro spinal cord
      preparations reveal defects in evoking rhythmic activity with N-methyl-DL
      aspartate and serotonin at lumbar, but not sacral roots. This is potentially
      significant, as functions involving sacral roots are spared at late stages of the
      disease. Moreover, electrical properties of SOD1 lumbar motoneurons are altered
      as early as the second postnatal week when mice begin to walk. Alterations
      concern the input resistance and the gain of SOD1 motoneurons which are lower
      than in control motoneurons. Whether or not the early changes in discharge firing
      are responsible for the uncoupling between motor axon terminals and muscles is
      still an open question. A link between these early electrical abnormalities and
      the late degeneration of motoneurons is proposed in this short review. Our data
      suggest that ALS, as other neurodegenerative diseases, could be a consequence of
      an abnormal development of neurons and network properties. We hypothesize that
      the SOD1 mutation could induce early changes during the period of maturation of
      motor systems and that compensatory mechanisms-linked to developmental spinal
      plasticity-might explain the late onset of the disease.

PMID- 16448810
TI  - Inspired oxygen fraction achieved with a portable ventilator: determinant
      factors.
AB  - INTRODUCTION: Non-invasive positive pressure ventilation (NIPPV) is an effective
      treatment in respiratory failure. Continuous positive pressure (CPAP) may also be
      useful in acute hypoxaemic patients. Supplementary oxygen is usually necessary in
      both systems. However, the inspired oxygen fraction (FiO2) delivered by a NIV
      portable ventilator is unknown. The main objectives of this study were to
      establish the maximal FiO2 that could be achieved by these devices and to analyse
      the FiO2 determinant factors. METHOD: Ten healthy volunteers were evaluated using
      a BiPAP ST30 ventilator (Respironics, USA) with a single-limb circuit, expiratory
      port and nasal mask (Respironics, USA). Oxygen (15 L/min) was administered at two
      connection points (proximal and distal). Each volunteer carried out a NIPPV
      (inspiratory pressure 20 cmH2O [1.95 kPa]-expiratory pressure 8 cmH2O [0.78 kPa])
      and a CPAP (10 cmH2O [0.981 kPa]) session. FiO2 was analysed by a probe located
      in the mask. Minute volume (MV) was measured using a pneumotachograph. RESULTS:
      Maximal FiO2 was obtained with CPAP and distal oxygen connection point (67.39 +/-
      15.39%). NIPPV achieved higher MV than CPAP. FiO2 was inversely correlated with
      MV. CONCLUSIONS: FiO2 obtained while using a NIPPV portable ventilator depends on
      the ventilatory assistant mode, the oxygen connection point and the MV reached.

PMID- 16448811
TI  - Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial
      epithelial cells.
AB  - Airway epithelial cells are the first targets of environmental stimuli and local
      cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis
      factor (TNF) in triggering IL-8 release has been documented previously. In this
      study, IL-8 mRNA and protein expression were examined in cultured human bronchial
      epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination
      with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a
      group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by
      ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and
      release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or
      PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of
      pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the
      presence of dexamethasone, budesonide, and fluticasone. Budesonide and
      fluticasone were 10-fold more potent than dexamethasone. The protein kinase C
      (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of
      pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study
      shows that PKC signal pathway seems to be involved in the pyocyanin-mediated
      upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells.
      These findings suggest that a vicious cycle perpetuating inflammation may exist
      in the biologic milieu of bronchiectatic patients infected with Pseudomonas
      aeruginosa due to the production of pyocyanin. The priming action of pyocyanin
      appears to be blocked by glucocorticoids, thus providing in vitro data in support
      of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.

PMID- 16448812
TI  - Utilization of municipal solid waste bottom ash and recycled aggregate in
      concrete.
AB  - In the combustion process of municipal solid waste (MSW), bottom ash (BA)
      represents the major portion of the solid residue. Since BA is composed of
      oxides, especially SiO(2) and CaO, the feasibility of its application in concrete
      as a substitute for cement was tested. It was found that at the age of 28 days,
      the flexural and compressive strengths of the binder linearly decrease at the
      rate of 0.03 and 0.02 MPa per wt% of BA in the binder, respectively. According to
      the results it may be recommended to replace up to 15 wt% of cement by BA and to
      use such binder where a low strength of concrete elements is required.
      Furthermore, the aggregate used for low strength concrete need not be of a very
      good quality. Therefore, gravel aggregate was partially replaced by recycled
      aggregate (RA). Consistency measured by slump was significantly reduced (>50%)
      when BA or/and RA were introduced into the mixture. However, concrete density and
      compressive strength were not affected and were approximately 2300 kg/m(3) and
      approximately 40 MPa, respectively.

PMID- 16448813
TI  - New redox mediator-modified polysulfone composite films for the development of
      dehydrogenase-based biosensors.
AB  - This work presents polysulfone membranes as new materials for the development of
      compact dehydrogenase-based biosensors. Composite films were prepared by mixing
      polysulfone with graphite and were deposited on epoxy-graphite composite
      electrodes. Redox mediators were successfully immobilized in the composite film
      leading to highly reproducible biosensors, without leakage of the immobilized
      species. This results in a more reliable analytical system as, at the same time,
      problems of electrode fouling related to the detection of the coenzyme
      nicotinamide adenine dinucleotide (NADH) on which is based the amperometric
      detection of dehydrogenase-based biosensors are avoided. Scanning electron
      microscopy was used to study the morphological characteristics of the surface and
      the cross-section of the polysulfone-graphite composite films. Several procedures
      to immobilize enzymes in these membranes were demonstrated. Glutamate
      dehydrogenase (GlDH) was immobilized as an example of dehydrogenase enzyme, in
      this case for the development of an ammonium biosensor. High sensitivity, good
      selectivity, wide linear ranges and short response times were obtained for the
      optimized sensors and biosensors. Their good performance combined with the
      simplicity of the construction method, make the polysulfone-graphite composite
      films attractive matrices for the development of new enzyme-based biosensors,
      especially those based on dehydrogenase enzymes.

PMID- 16448814
TI  - Image-detected 'probably benign' breast lesions: a significant reason for
      referral from primary care.
AB  - In Australia, and many health care provider systems, primary care physicians are
      the first to see women with breast symptoms and are responsible for making
      decisions on whether to investigate and when to refer to specialist teams. We
      present an audit of new patient referrals from primary care triaged to a 'low
      risk' (low likelihood of cancer) clinic on the basis of benign findings. The most
      common reason for referral was 'breast lump' (38%) followed by 'image-detected'
      abnormality (26%.) We have identified that (outside of population screening
      services) many women are being referred from primary care to specialist clinics
      for management of screen-detected lesions considered benign on imaging. Further
      research is needed to identify the reasons for such referrals and to develop
      appropriate educational strategies and clinical policy, both for the primary care
      and the specialist breast practitioner.

PMID- 16448815
TI  - Intraductal papilloma in a reconstructed breast: mammographic and sonographic
      appearance with pathologic correlation.
AB  - The usual abnormal mammographic and sonographic findings encountered after
      reconstruction with autologous myocutaneous flaps for breast carcinoma, include
      fat necrosis, calcifications, lymphedema, and locally recurrent carcinoma. This
      case report describes a case of an intraductal papilloma occurring in a
      reconstructed breast in a 48-year-old woman who underwent a left-sided mastectomy
      for recurrent ductal carcinoma in situ followed by immediate reconstruction with
      a supercharged transverse rectus abdominal muscle flap. The role of imaging in
      the detection and management of occult or clinically palpable abnormalities in
      reconstructed breasts is discussed.

PMID- 16448816
TI  - Gender differences in post-exercise sagittal knee translation: a comparison
      between elite volleyball players and swimmers.
AB  - BACKGROUND: There is an increased risk for anterior cruciate ligament injury
      during the last part of a match or training session and one reason for that could
      be a post-exercise increase in tibial translation. PURPOSE: To investigate if
      sagittal tibial translation is affected after a workout session in volleyball or
      swimming in elite athletes. In addition, gender differences in sagittal tibial
      translation after the workout session were investigated. METHOD: Thirty-one elite
      volleyball players (16 male) and 33 elite swimmers (15 male) participated in this
      study. Measurements of total tibial translation were taken before and after a
      workout session in either volleyball or swimming with the use of a KT-1000
      arthrometer. RESULTS: Total tibial translation increased by 1.1 mm (SD 1.9) in
      the group consisting of both male and female volleyball players (p=0.003) and
      remained unchanged in the swimmers. Male athletes increased their tibial
      translation with 1.8 mm (SD 1.8) and 0.6 mm (SD 1.1) in the two sports,
      respectively, while the tibial translation did not increase in the female
      athletes. CONCLUSION: Impact sports such as volleyball training leads to a post
      exercise increase in tibial translation in male athletes. The increase in tibial
      translation in swimmers, that is a non-impact sport, was small and may not be
      clinically significant for the functional stability of the joint. It has been
      shown that female athletes have an increased risk for injury. Our results show no
      support for an increase in tibial translation being an important factor for this
      increased risk, and suggest that the difference between males and females in this
      regard should be sought elsewhere.

PMID- 16448817
TI  - Cruciate ligament assessment in MRI scans: a pilot study of a static drawer
      technique.
AB  - Ten subjects with cruciate ligament rupture (five ACL and five PCL), and four
      normal subjects underwent magnetic resonance imaging (MRI) with a novel splint
      that stresses the knee. The splint acted as a fulcrum to translate the tibia in
      an anterior and posterior direction, depending on application. The MRI images
      showed that translation of the tibial plateaux occurred but not in a simple
      manner. The resultant images did not show marked anterior tibial translation in
      the ACL ruptured knee with an anterior drawer, nor posterior tibial translation
      for the PCL injured knee in posterior drawer. The medial plateau tended to move
      posteriorly in anterior drawer in the normal knees. The secondary MRI findings of
      ACL injury and associated meniscal injuries were enhanced. A further study with
      50 subjects in each group, and arthroscopic confirmation of the findings, would
      be required to confirm these results.

PMID- 16448818
TI  - Chromosomal differentiation of populations of Lysapsus limellus limellus, L. l.
      bolivianus, and of Lysapsus caraya (Hylinae, Hylidae).
AB  - Cytogenetic analysis were done on specimens from two populations of Lysapsus
      limellus limellus, three of L. l. bolivianus and of one of Lysapsus caraya. All
      animals showed a diploid chromosomal number of 2n=24. The karyotypes of the two
      L. limellus subspecies were very similar, differing only by the larger amount of
      telomeric heterochromatin and a small pericentromeric C-band on the short arms of
      pair 2 in L. l. limellus specimens. The karyotype of L. caraya differed from
      those of the two L. limellus subspecies in terms of chromosomal morphology, C
      banding pattern and location of the main NOR on chromosomes 7 and 6,
      respectively. The karyotype of the L. l. bolivianus population from Guajara
      Mirim/RO differed from those of the other populations of the same subspecies in
      morphology and heterochromatin pattern of chromosomes 7 and 8. Additional NORs
      were detected by silver staining and confirmed by FISH in one of the homologues
      of pairs 1 and 8 in L. l. bolivianus and in pair 7 in L. caraya. These results
      suggest that a reassessment of the taxonomic status of L. limellus subspecies,
      especially of the L. l. bolivianus populations, may be necessary.

PMID- 16448819
TI  - In situ determination of salinity by PGNAA.
AB  - Salinity is a very important environmental issue all around the world. In many
      cases salinity was produced from human activities like farming and mining.
      Different soluble salts contribute to salinity, however, NaCl is the most common
      salt producing salinity. This work deals with the application of the prompt gamma
      neutron activation analysis (PGNAA) technique for in situ determination of
      salinity. The technique is based on the measurement of chlorine, a component of
      the common salt, by PGNAA.

PMID- 16448820
TI  - Reduction in maximal firing rate of motoneurons after 1-week immobilization of
      finger muscle in human subjects.
AB  - We investigated the effects of immobilization on the maximal motoneuronal firing
      rate recorded from the first dorsal interosseous (FDI) during voluntary isometric
      contraction. In five human subjects, the middle finger, index finger, and thumb
      were immobilized for 1 week in a fiber-glass cast, which kept FDI in a shortened
      position. During a maximal voluntary contraction, single muscle-fiber action
      potentials were recorded using a tungsten microelectrode, and mean firing rate
      was calculated for each action-potential train. Three recording sessions were
      held: before immobilization (pre), after immobilization (post), and after a 1
      week recovery period (recovery). The mean firing rate of FDI motoneurons during
      maximal voluntary contraction was decreased immediately after the 1-week
      immobilization (pre: 39.0+/-3.2 Hz, number of detected spike trains (n)=353;
      post: 33.1+/-1.5 Hz, n=285; p<0.05), and there was a return to control after the
      recovery period (40.2+/-3.4 Hz, n=236). This suggests that the maximal
      motoneuronal firing rate achieved during maximal voluntary contraction is reduced
      after short-term immobilization. The functional implications and the contribution
      of this phenomenon to the immobilization-induced reduction in maximal voluntary
      force are discussed.

PMID- 16448821
TI  - Mapping radiation dose distribution on the fractional anisotropy map:
      applications in the assessment of treatment-induced white matter injury.
AB  - We describe a method to map whole brain radiation dose distribution on to
      diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its
      applications for studying dose-effect relationships and regional susceptibility
      in two childhood medulloblastoma survivors. To determine the FA changes voxel-by
      voxel in white matter, the post-treatment follow-up FA maps were coregistered to
      baseline pre-treatment FA maps and automatic segmentation for white matter was
      carried out. DeltaFA maps representing relative FA change in white matter were
      hence generated for visual inspection and quantitative analysis. The radiation
      dose distribution, calculated from radiotherapy plan and exported as images, was
      coregistered to baseline FA images. DT-MR imaging and processing noise was small
      with root mean square value of 1.49% for mean DeltaFA. We evaluated the mean
      DeltaFA changes of regions-of-interest according to radiation dose regions to
      provide an estimate of the dose-response and found increasing reduction in mean
      DeltaFA with increasing radiation dose up to 45 Gy after which there was a
      reversal in the mean FA trend and mean FA approached baseline value. We also
      found more severe mean FA reduction in the frontal lobes compared to the parietal
      lobes despite the same radiation dose, suggesting regional susceptibility in the
      frontal lobe, and mean FA increase in the brainstem after radiation in both
      patients. We conclude that the method described may be useful in estimating dose
      effect relationships and studying regional susceptibility of the brain to
      radiation in medulloblastoma survivors.

PMID- 16448822
TI  - A novel terminal differentiation model of human articular chondrocytes in three
      dimensional cultures mimicking chondrocytic changes in osteoarthritis.
AB  - This study establishes a cell culture model mimicking the terminal
      differentiation occurring in osteoarthritic chondrocytes. Normal articular
      chondrocytes obtained from human knees treated with 5-azacytidine (Aza-C) were
      harvested 3, 7 and 14 days after treatment. Phenotypic and genetic changes of
      articular chondrocytes were detected. The results show that mRNA expression of
      collagen type II, a marker for normal functional articular chondrocytes, was
      significantly decreased after Aza-C treatment in comparison to the control
      cultures, while those of collagen type X and ALP, markers for hypertrophic
      chondrocytes, were significantly increased. Cell size and apoptotic rate of
      articular chondrocytes showed significant increases compared to the control after
      14 days of Aza-C treatment. Terminal differentiation is shown by this model of
      three-dimensional cultured human articular chondrocytes, which could apply to the
      studies of the cellular mechanisms of osteoarthritis.

PMID- 16448823
TI  - Role of the actin cytoskeleton during respiratory burst in chemoattractant
      stimulated neutrophils.
AB  - The aim of this study was to clarify the role of the actin cytoskeleton during
      chemotactic peptide fMet-Leu-Phe (fMLF)-stimulated respiratory burst in human
      neutrophil granulocytes. Reactive oxygen species (ROS) was measured as luminol
      amplified chemiluminescence (CL) and F-actin content as bodipy phallacidin
      fluorescence in neutrophils treated with latrunculin B or jasplakinolide, an
      inhibitor and activator of actin polymerization, respectively. Latrunculin B
      markedly decreased, whereas jasplakinolide increased, the F-actin content in
      neutrophils, unstimulated or stimulated with fMLF. Latrunculin B enhanced the
      fMLF-triggered ROS-production more than tenfold. Jasplakinolide initially
      inhibited the fMLF-induced CL-response, however, caused a potent second sustained
      phase (>400% of control). Both actin drugs triggered a substantial CL-response
      when added 5-25 min after fMLF. This was also valid for chemotactic doses of
      fMLF, where latrunculin B and jasplakinolide amplified the ROS-production 5-10
      times. By using specific signal transduction inhibitors, we found that the NADPH
      oxidase activation triggered by destabilization of the actin cytoskeleton occurs
      downstream of phospholipase C and protein kinase C but is mediated by Rho GTPases
      and tyrosine phosphorylation. In conclusion, rearrangements of the actin
      cytoskeleton are a prerequisite in connecting ligand/receptor activation,
      generation of second messengers and assembly of the NADPH oxidase in neutrophil
      granulocytes.

PMID- 16448824
TI  - Improved activity of streptozotocin-selected insulinoma cells following
      microencapsulation and transplantation into diabetic mice.
AB  - We have recently shown that repeated streptozotocin (STZ) treatment induces the
      selection of insulinoma cells (RINmS) with both improved resistance to
      diabetogenic toxins and functional activity, compared to parental RINm cells. The
      aim of the present study was to estimate the potential of RINmS cells to maintain
      their engineered characteristics during in vivo hyperglycemic conditions. It was
      found that microencapsulation and transplantation into diabetic mice preserved a
      three-fold higher level of insulin content in selected RINmS cells when compared
      to the parental ones. Retrieval of transplanted encapsulated cells from the
      peritoneal cavity of diabetic mice had a significantly higher insulin content and
      a more intense insulin response to secretogogues in selected RINmS cells when
      compared to retrieved RINm cells. In conclusion, our results show that RINmS
      cells do not lose their improved functional characteristics after encapsulation
      and transplantation into diabetic mice.

PMID- 16448825
TI  - Cyclic adenosine 3',5'-monophosphate induces differentiation of mouse embryonic
      stem cells into cardiomyocytes.
AB  - Embryonic stem (ES) cells, derived from blastocyst-stage of early mammalian
      embryos, have the potential to differentiate into derivatives of all three
      embryonic germ layers. Here we reported the first evidence that murine
      pluripotent ES cells could be induced to differentiate into cardiomyocytes by
      cyclic adenosine 3',5'-monophosphate (cAMP) in vitro. Spontaneously beating of
      cardiac cell clusters began to be observed within the outgrowths of embryoid
      bodies (EBs) as early as 2 days after the onset of differentiation. By days 5-8
      after induction, a maximum level of cardiomyocyte differentiation could be
      achieved. Incubation of EBs with cAMP at concentrations ranging from 0.01 mg/L to
      1 mg/L resulted in a significant elevation in differentiation rate, reaching a
      maximum value of 44.0 +/- 1.3% at 0.03 mg/L of exposure. At 0.03 mg/L
      concentration point, an approximately 8.1-fold increase in cardiomyocyte
      differentiation was observed in comparison with 5.4 +/- 0.9% of untreated
      controls. The differentiation rate induced by cAMP was shown to be similar to
      that of RA/DMSO treated controls, indicating that cAMP has the same inducing
      effect as RA/DMSO. However, no significant co-inducing effects between cAMP and
      RA/DMSO were seen. Cardiomyocytes were evident as they expressed cardiac cell
      specific genes and protein markers including GATA4, Nkx2.5, beta-MHC, atrial
      natriuretic factor (ANF) and alpha-actin when analyzed by reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemical staining. The results
      from the present study suggested a novel role of cAMP in cardiomyocyte
      differentiation and provided a new research model for the study of cardiac cell
      biology.

PMID- 16448826
TI  - The effect of p21 antisense oligodeoxynucleotides on the radiosensitivity of
      nasopharyngeal carcinoma cells with normal p53 function.
AB  - OBJECTIVE: p21(WAF1/CIP1) is transcriptionally activated by p53 and is required
      for G1 to S phase progression. p21 plays a critical role in DNA repair after DNA
      damage. Thus, cells with defective p21 may result in an enhancement of radiation
      induced apoptosis and improved radiosensitivity. We tested the hypothesis that
      p21 antisense oligodeoxynucleotides (p21 AS ODNs) can be used to reduce p21
      expression level and increase radiosensitivity in CNE-1-wtp53 nasopharyngeal
      carcinoma cell line with normal p53 function. METHODS AND MATERIALS: The p21
      antisense oligodeoxynucleotides (p21 AS ODNs) and the random control
      oligodeoxynucleotides (p21 RD ODNs) were synthesized. p21 AS ODNs sequence: 5'
      TGTCATGCTGGTCTGCCGCC-3'; p21 RD ODNs sequence: 5'-CCGGTGAACGAGCGAGCACA-3'. p21 AS
      ODNs and p21 RD ODNs were transfected into CNE-1-wtp53 nasopharyngeal carcinoma
      cell line. The protein expression levels of P21 were evaluated using Western
      blotting analysis. Cell cycle progression and apoptotic cells were assessed by
      flow cytometric analysis. The clonogenic survival assay was performed to
      determine the survival fraction. The parameters D0, Dq, and N for the single-hit
      multitarget model and the parameters alpha, beta, alpha/beta, and SF2 for the
      linear-quadratic model were calculated. BALB/c nude mice were used to investigate
      the effect of p21 AS ODNs on the radiosensitivity of nasopharyngeal xenografts in
      vivo. RESULTS: p21 AS ODNs were detected mainly in plasma with fluorescence
      microscopy investigation. P21 protein level dramatically decreased and the amount
      of apoptotic cells increased in p21 AS ODNs transfected cells than in p21 RD ODNs
      transfected cells after irradiation. The percentage of G1 arrest decreased in p21
      AS ODNs transfected cells 24 h after radiation, then G2 arrest decreased 48 h
      after radiation. The values of D0, Dq, SF2 decreased and alpha value increased in
      p21 AS ODNs transfected cells than in control cells. The inhibition rate in tumor
      xenografts exposed to X ray of 10 Gy alone was 39.1%, while it was 51.4% in
      xenografts injected with p21 AS ODNs before exposure to radiation. Unfortunately,
      there was no significant difference between these two groups (P < 0.05).
      CONCLUSION: p21 Antisense oligodeoxynucleotides led to inhibition of P21 protein
      expression, loss of G1 arrest, increase of apoptosis in CNE-1-wtp53
      nasopharyngeal carcinoma cell line in vitro and inhibited tumor growth in vivo.
      Antisense oligodeoxynucleotides may become a promising strategy to enhance
      radiosensitivity in nasopharyngeal carcinoma cells with normal p53 function.

PMID- 16448828
TI  - TTM-based counselling in physiotherapy does not contribute to an increase of
      adherence to activity recommendations in older adults with chronic low back pain-
      a randomised controlled trial.
AB  - AIMS: The present study examines the outcome of counselling in physiotherapy
      based on the Transtheoretical Model (TTM) in a sample of elderly individuals with
      chronic low back pain. METHODS: In a prospective randomised trial with concealed
      assignment, elderly individuals with chronic low back pain were allocated to two
      treatment conditions. Both contained 10 sessions of physiotherapy, each of 20min
      duration. In addition, the experimental group (EG) received 10min counselling
      prior to every session based on the TTM, also provided by the physiotherapist,
      and the control group (CG) underwent a placebo ultrasound treatment with an
      inactivated device to control for the additional attention given to the EG.
      Assessments took place prior to the treatment (t1), immediately after termination
      of the treatment (t2), and at a 6-months follow-up. Outcome measures were
      physical activity calculated from one-week activity diaries, self-reported
      functional capacity, and range of motion measured by ultrasound topometry.
      RESULTS: A total of 170 individuals (64% female) with a mean age of 70.3 years
      (SD=4.4, range 65-84) participated in the study. The retention rate was 90%. At
      t3, both EG and CG showed increased physical activity and functional capacity,
      but no change in range of motion. Effect sizes were large. Contrary to our
      hypothesis, however, motivational training did not result in a better outcome
      compared with placebo treatment. CONCLUSION: The study does not provide evidence
      that a short TTM-based motivation programme is superior to placebo treatment
      regarding adherence to activity recommendations.

PMID- 16448827
TI  - Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit
      tolerance to spinal morphine in the rat.
AB  - Chronic use of opioid is associated with pro-nociceptive phenomena such as
      hyperalgesia or tolerance. The interaction between opioid and non-steroidal anti
      inflammatory drugs (NSAIDs) with respect to opioid-associated hyperalgesia and
      tolerance remains largely unknown. This study examines the effect of subcutaneous
      or intrathecal administration of ketorolac, an NSAID, on recurrent withdrawal
      induced hyperalgesia and tolerance to spinal morphine in rats. Animals were
      infused with morphine intrathecally, and daily subcutaneous naloxone was used for
      recurrent withdrawal purpose. We observed that escape latencies on hot box were
      decreased in animals subjected to withdrawal, and this decrease was reversed by
      subcutaneous ketorolac pretreatment. In addition, we observed that recurrent
      withdrawal did not significantly affect the magnitude of spinal morphine
      tolerance. Compared to controls, all morphine infused animals showed similar
      changes in their dose responses to spinal morphine, effective dose 50 values and
      tolerance ratios; and these changes were not affected by the ketorolac given
      subcutaneously. The effect of ketorolac on tolerance was further examined by
      directly delivering ketorolac to the spinal cord, and again we observed similar
      changes in the daily latency, percentage of area under the curve and percentage
      of maximal possible effects among groups infused with morphine, regardless of
      intrathecal ketorolac treatment. Together, our results demonstrate that recurrent
      withdrawal is associated with hyperalgesia but this has no effect on the
      tolerance development; ketorolac protects against recurrent withdrawal induced
      hyperalgesia without significantly altering spinal morphine tolerance.

PMID- 16448829
TI  - Multifrequency simulations of the EPR spectra of lipid spin labels in membranes.
AB  - Simulations are performed of 34- and 9-GHz EPR spectra, together with 94-GHz EPR
      spectra, from phospholipid probes spin-labelled at the C4-C14 positions of the sn
      2 chain, in liquid-ordered and gel-phase membranes of dimyristoyl
      phosphatidylcholine with high and low cholesterol contents. The multifrequency
      simulation strategy involves: (i) obtaining partially averaged spin-Hamiltonian
      tensors from fast-motional simulations of the 94-GHz spectra; (ii) performing
      slow-motional simulations of the 34- and 9-GHz spectra by using these pre
      averaged tensors with the stochastic Liouville formalism; (iii) constructing, by
      simulation, slow-motional calibrations for the differences, DeltaA(zz)(qx) and
      Deltag(zz)(qx), in effective A(zz)-hyperfine splittings and g(zz)-values between
      34- (or 94-GHz) and 9-GHz spectra; (iv) using such calibrations for
      DeltaA(zz)(qx) and Deltag(zz)(qx) and dynamic parameters from stage (ii) as a
      guide to adjust the extent of pre-averaging of the spin-Hamiltonian tensors; and
      (v) repeating the 34- and 9-GHz simulations of stage (ii). By using this scheme
      it is possible to obtain consistent values of the rotational diffusion
      coefficients, D(R perpendicular) and D(R//), and the long-axis order parameter,
      S(zz), that characterize the slow axial motion of the lipid chains, from spectra
      at both 34 and 9GHz. Inclusion of spectra at 34GHz greatly improves precision in
      determining the D(R//) element of the slow diffusion tensor in these systems.

PMID- 16448830
TI  - Optimum spin-state selection for all multiplicities in the acquisition dimension
      of the HSQC experiment.
AB  - Most conventional heteronuclear spin-state-selective (S(3)) NMR experiments only
      work for a specific multiplicity, typically IS spin systems. Here, we introduce a
      general and efficient IPAP strategy to achieve S(3) editing simultaneously for
      all multiplicities in the acquisition dimension of the HSQC experiment.
      Complementary in-phase (HSQC-IP) and anti-phase (HSQC-AP) data are separately
      recorded with a simple phase exchange of two 90 degrees proton pulses involved in
      the mixing process of the F2-coupled sensitivity-improved HSQC pulse sequence.
      Additive and subtractive linear combination of these IP/AP data generates
      simplified F2-alpha/beta-spin-edited HSQC subspectra for all IS, I(2)S, and I(3)S
      spin systems and combines enhanced and optimized sensitivity with excellent
      tolerance to unwanted cross-talk contributions over a considerable range of
      coupling constants. Practical aspects such as pulse phase settings, transfer
      efficiency dependence, inter-pulse delay optimization, and percentage of cross
      talk are theoretically analyzed and discussed as a function of each I(n)S
      multiplicity. Particular emphasis on the features associated to spin-editing in
      diastereotopic I(2)S spin systems and application to the measurement of long
      range proton-carbon coupling constants are also provided.

PMID- 16448832
TI  - Placentation in the degu (Octodon degus): analogies with extrasubplacental
      trophoblast and human extravillous trophoblast.
AB  - This study examined the placentation in the degu, the origin of the
      extrasubplacental trophoblast (EST) (extravillous trophoblast in human), and the
      activity of Na+/K+ ATPase in the placental barrier during different gestational
      ages, as part of a wider effort to understand the reproductive biology of this
      species. Fifteen degus at the first stage of gestation, midgestation and at term
      of pregnancy were studied. At day 27 of gestation, the subplacenta is formed
      under the wall of the central excavation. Simultaneously, the outermost
      trophoblast of the ectoplacental cone differentiated into secondary trophoblast
      giant cells that lie on the outside of the placenta, forming an interface with
      the maternal cells in the decidua. These giant cells immunostained positive for
      cytokeratin (CK) and placental lactogen (hPL) until term. During this period, the
      EST merged from the subplacenta to the decidua and immunostained negative for CK,
      but at term, immunostained for CK and hPL in the maternal vessels. The vascular
      mesenchyme of the central excavation invaded the chorioallantoic placenta during
      this period, forming two fetal lobules of labyrinthine-fine syncytium, the zone
      of the placental barrier. The activity of Na+/K+ ATPase in the placental barrier
      was constant during the gestational period. The residual syncytium at the
      periphery of the placental disc and between the lobules was not invaded by fetal
      mesenchyme and formed the marginal and interlobular labyrinthine syncytium that
      immunostained first for CK, and later for hPL, as in the labyrinthine fine
      syncytium. The presence of intracytoplasmic electron-dense material in the
      interlobular labyrinthine syncytium suggested a secretory process in these cells
      that are bathed in maternal blood. Placentas obtained from vaginal births
      presented a large, single lobe, absence of the subplacenta, and a reduced
      interlobular labyrinthine syncytium. At day 27, the inverted visceral yolk sac is
      observed and its columnar epithelium immunostained for CK and hPL. This suggests
      that the yolk sac is an early secretory organ. The epithelium of the parietal
      yolk sac covers the placenta. The origin of the EST in the degu placenta and its
      migration to maternal vessels allows us to present this animal model for the
      study of pregnancy pathologies related to alterations in the migration of the
      extravillous trophoblast.

PMID- 16448831
TI  - Effects of inhaled eotaxin on airway function and inflammatory cell influx in
      sensitised and non-sensitised guinea pigs.
AB  - Eotaxin is a chemokine that has high potency and selectivity as a chemoattractant
      agent for eosinophils, signalling exclusively through the CCR3 receptor. Eotaxin
      is upregulated in the lungs within 3 h of antigen challenge, levels peak at 6 h
      in lung tissue and bronchoalveolar (BAL) fluid, and fall within 12 h of exposure.
      This study aimed to look at the effect(s) of eotaxin inhalation on airway
      function in guinea pigs, to determine if the expected inflammatory cell
      (eosinophil) infiltration could induce airway hyperreactivity (AHR) and a
      bronchoconstrictor response equivalent to the late asthmatic response (LAR) seen
      after antigen challenge. Animals were sensitised with 100 microg/ml OA with a
      dose on days 1 and 5. Airway responses to inhaled eotaxin (10 or 20 microg/ml)
      were determined by whole body plethysmography as the change in specific airway
      conductance (sGaw). Inhaled histamine (1mM) was used to investigate AHR, and cell
      influx was determined by BAL. Senitised animals exposed to 10 microg/ml eotaxin
      did not reveal a bronchoconstrictor response or AHR and cellular infiltration to
      the lungs was not evident 24 h after exposure. Both sensitised and non-sensitised
      animals exposed to 20 microg/ml eotaxin however revealed a significant
      bronchoconstrictor response 6h post-challenge, with reductions in sGaw of -27.0+/
      6.6% and -32.3+/-6.8%, respectively. Both groups also displayed a
      bronchoconstrictor response to inhaled histamine 24h after exposure, indicating
      AHR, and a significant increase in both total and differential cell counts.
      Sensitised animals, however, revealed a significant increase in cell influx
      compared to non-sensitised animals. Nebulised eotaxin can reveal a LAR, AHR to
      inhaled histamine, and cellular infiltration to the lungs, possibly via the
      mobilisation of eosinophils from the bone marrow, and their subsequent
      recruitment to the airways.

PMID- 16448833
TI  - Oxygen uptake, diffusion limitation, and diffusing capacity of the bipectinate
      gills of the abalone, Haliotis iris (Mollusca: Prosobranchia).
AB  - Extant abalone retain an ancestral system of gas exchange consisting of paired
      bipectinate gills. This paper examines the hypothesis that fundamental
      inefficiencies of this arrangement led to the extensive radiation observed in
      prosobranch gas exchange organs. Oxygen uptake at 15 degrees C was examined in
      the right gill of resting adult blackfoot abalone, Haliotis iris Martyn 1784. Pre
      and post-branchial haemolymph and water were sampled and oxygen content, partial
      pressure (Po2), pH, and haemocyanin content measured; in vivo haemolymph flow
      rate was determined by an acoustic pulsed-Doppler flowmeter. During a single pass
      across the gills, mean seawater Po2 fell from 138.7 Torr to 83.4 Torr, while
      haemolymph Po2 rose from 37.2 Torr to 77.0 Torr raising total O2 content from
      0.226 to 0.346 mmol L(-1). Haemolymph flowed through the right gill at a mean
      rate of 9.6 mL min(-1) and carried 0.151 to 0.355 mmol L(-1) of haemocyanin (mean
      body mass 421 g). Only 34.7% of the oxygen carried in the arterial haemolymph was
      taken up by the tissues and less than half of this was contributed by
      haemocyanin. A diffusion limitation index (Ldiff) of 0.47-0.52, a well-matched
      ventilation-perfusion ratio (1.2-1.4) and a diffusing capacity (D) of 0.174
      micromol O2 kg(-1) Torr(-1) indicate that the gills operate efficiently and are
      able to meet the oxygen requirements of the resting abalone.

PMID- 16448834
TI  - Metabolic measures of male southern toads (Bufo terrestris) exposed to coal
      combustion waste.
AB  - Southern toads (Bufo terrestris) are found in coal fly ash collection basins
      associated with coal-burning electrical power plants. These basins contain large
      amounts of trace metals and organisms found in these basins are known to
      accumulate large quantities of metals. Studies on a variety of organisms exposed
      to trace metals found that they experience a significant increase in standard
      metabolic rate. We experimentally exposed southern toads to metal-contaminated
      sediment and food and measured changes in standard and exercise metabolic rates
      as well as changes in body, liver and muscle mass, blood glucose, and
      corticosterone. We found that toads exposed to trace metal contamination gained
      significantly less mass (18.3 %) than control toads (31.3%) when food was limited
      and experienced significantly decreased RQ after exercise. However, contaminated
      toads did not experience changes in standard (x control = 0.114 +/- 0.016 mL O2
      g(-1) h(-1); x (ash)=0.109 +/- 0.013 mL O2 g(-1) h(-1), p = 0.08) or exercise
      metabolic rates (x control = 0.53 +/- 0.06 mL O2 g(-1) h(-1); x ash =0.44 +/-
      0.04 mL O2 g(-1) h(-1), p = 0.47) plasma glucose levels (p = 0.6), and hepatic or
      muscle percentage indices (p > 0.2 in all cases) whether food was limited or not.

PMID- 16448836
TI  - Quantitative determination of succinylacetone in dried blood spots for newborn
      screening of tyrosinemia type I.
AB  - BACKGROUND: Tyrosinemia type I (TYR 1) is a severe disorder causing early death
      if left untreated. While tyrosine can be determined in dried blood spots (DBS),
      it is not a specific marker for TYR 1 and most often associated with benign
      transient tyrosinemia of the newborn. Succinylacetone (SUAC) is a specific marker
      for TYR 1 but not detectable by routine newborn screening. We developed a new
      assay that determines SUAC in DBS by liquid-chromatography tandem mass
      spectrometry (LC-MS/MS). METHODS: Whole blood is eluted from a 3/16-in. DBS by an
      aqueous solution containing deuterium labeled SUAC as internal standard (IS).
      SUAC and IS are oximated, then extracted, butylated, and analyzed by LC-MS/MS.
      Quantitation is from SUAC spiked calibrator DBS over the range 0-200 microM using
      selected reaction monitoring of transitions m/z 212 to 156 and m/z 214 to 140 for
      SUAC and IS, respectively. Analysis time is 5 min. To assess the effectiveness of
      a two-tier screening approach for TYR 1 we applied this assay to our newborn
      screening program over the last 15 months. RESULTS: The intra-assay precision was
      determined for three different levels of SUAC (5, 20, and 50 micromol/L) and the
      CV calculated to be 4.7, 2.6, and 3.1%, respectively (n=5). Inter-assay precision
      CVs were 12.7, 8.2, and 7.8%, respectively on the same samples. SUAC levels in
      DBS from 10 confirmed TYR 1 cases not treated with 2-(2-nitro-4
      trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) were clearly abnormal (16-150
      micromol/L; mean: 61 micromol/L; controls: <5 micromol/L). Over a 15-month
      period, SUAC was determined in newborn screening samples with elevated tyrosine
      concentrations when applying different cut off values until it was settled at 150
      micromol/L. No case of TYR 1 was detected in 124,780 newborns tested. CONCLUSION:
      We have developed a new LC-MS/MS based method for the determination of SUAC in
      DBS. This assay has the potential to significantly reduce the number of false
      positive results in newborn screening for TYR 1 and can also be used for the
      laboratory follow up of patients treated for TYR 1.

PMID- 16448835
TI  - Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are
      affected by age and copper status in rats and mice.
AB  - In an attempt to identify a sensitive and improved marker of mammalian copper
      status during neonatal development experiments compared two plasma cuproenzymes,
      peptidylglycine alpha-amidating monooxygenase (PAM ), an enzyme involved in
      peptide posttranslational activation, to ceruloplasmin (Cp), a ferroxidase
      involved in iron mobilization. Dietary Cu deficiency (Cu-) was studied in dams
      and offspring at postnatal age 3 (P3), P12, and P28. Rodent Cp activity rose
      during lactation whereas PAM activity fell. Reduction in Cp activity was more
      severe than reduction in PAM activity in Cu- offspring and dams. Cp activity was
      greater in rats than mice whereas PAM activity was similar in adults but greater
      in mouse than rat pups. Both cuproenzymes changed during neonatal development and
      when dietary copper was limiting. With proper controls, each enzyme can be used
      to assess copper status.

PMID- 16448837
TI  - Epidemiology of corynebacterial urinary infections.

PMID- 16448838
TI  - Prevalence of hepatitis B among Afghan refugees living in Balochistan, Pakistan.
AB  - OBJECTIVE: Continued civil war and political instability in Afghanistan have lead
      to a huge influx of refugees into the neighboring provinces in Pakistan. This
      study was conducted to estimate seroprevalence of hepatitis B and to identify
      potential risk factors for hepatitis B virus (HBV) transmission among the
      refugees living in the camps of Balochistan Province, Pakistan. METHODS: A cross
      sectional survey of hepatitis B surface antigen (HBsAg) was conducted during
      October 2003. We obtained the registration list to select families randomly from
      the refugee camps. A husband, wife and one of their children, selected at random,
      were enrolled in the study. Study subjects with positive laboratory results for
      HBsAg were compared with those who were negative for HBsAg. RESULTS: Field
      workers interviewed 301 families with a total of 903 study subjects. Blood
      specimens of 75 study subjects (8.3%, 95% CI 6.6-10.3) were positive for HBsAg.
      There were 37 husbands (12.3%, 95% CI 7.2-14.4) and 21 wives (7.0%, 95% CI 4.5
      10.6) positive for HBsAg. Out of 301 children, 17 (5.6%, 95% CI 3.4-9.1) were
      positive for HBsAg. Receiving more than ten injections during the previous year
      increased the risk of HBV infection (OR 3.5, 95% CI 1.8-6.7). A child positive
      for HBsAg was more likely to have a positive parent compared to an HBsAg negative
      child (OR 5.7, 95% CI 2.0-16.5). CONCLUSION: Hepatitis B is highly endemic among
      Afghan refugees living in these camps. Unsafe injection practices will continue
      to cause a steady increase in the magnitude of this health problem until
      appropriate control measures are taken. The possibility of mother-to-child
      transmission underscores the need to include vaccination against hepatitis B as
      part of routine immunization in this population.

PMID- 16448839
TI  - Reasons for the increase in emerging and re-emerging viral infectious diseases.
AB  - In the past two decades, humans have faced many new viral infectious agents in
      emerging and re-emerging infectious diseases (EIDs). Many factors contribute to
      the appearance of EIDs. These factors are complex but can be classified into
      three different categories: virus factors, human factors, and ecological factors.
      The factors contributing to the cause of such viral infectious diseases will be
      systematically reviewed in this article.

PMID- 16448840
TI  - Dryness symptoms among an unselected clinical population with and without contact
      lens wear.
AB  - Dry Eye Questionnaire (DEQ) and Contact Lens Dry Eye Questionnaire (CLDEQ) from
      unselected eye care patients (including current, former and non-contact lens
      wearers) were analyzed to contrast dryness symptoms among patients with and
      without contact lenses. Contact lens wearers reported a higher incidence of
      intense symptoms, especially late in the day (12.7% AM versus 41.1% PM, p <
      0.0001), that diminished when they removed lenses (p = 0.0001). Dryness intensity
      was not correlated with gender and was inversely correlated with age among
      contact lens wearers, differing significantly from the pattern among non-lens
      wearers. Contact lens related dryness differs from dry eye among non-lens
      wearers.

PMID- 16448841
TI  - 4-nitroquinoline-1-oxide induced experimental oral carcinogenesis.
AB  - Human oral cancer is the sixth largest group of malignancies worldwide and single
      largest group of malignancies in the Indian subcontinent. Seventy percent of
      premalignant cancers appear from premalignant lesions. Only 8-10% of these
      lesions finally turn into malignancy. The appearance of these premalignant
      lesions is one distinct feature of human oral cancer. At present there is dearth
      of biomarkers to identify which of these lesions will turn into malignancy.
      Regional lymph node metastasis and locoregional recurrence are the major factors
      responsible for the limited survival of patients with oral cancer. Paucity of
      early diagnostic and prognostic markers is one of the contributory factors for
      higher mortality rates. Cancer is a multistep process and because of constrain in
      availability of human tissues from multiple stages of oral carcinogenesis
      including normal tissues, animal models are being widely used, aiming for the
      development of diagnostic and prognostic markers. A number of chemical
      carcinogens like coal tar, 20 methyl cholanthrene (20MC), 9,10-dimethyl-1,2
      benzanthracene (DMBA) and 4-nitroquinoline-1-oxide (4NQO) have been used in
      experimental oral carcinogenesis. However, 4NQO is the preferred carcinogen apart
      from DMBA in the development of experimental oral carcinogenesis. 4NQO is a water
      soluble carcinogen, which induces tumors predominantly in the oral cavity. It
      produces all the stages of oral carcinogenesis and several lines of evidences
      suggest that similar histological as well as molecular changes are observed in
      the human system. In the present review an attempt has been made to collate the
      information available on mechanisms of action of 4NQO, studies carried out for
      the development of biomarkers and chemopreventives agents using 4NQO animal
      models.

PMID- 16448842
TI  - The SHAP-hyaluronan complex in serum from patients with chronic liver diseases
      caused by hepatitis virus infection.
AB  - Our previous study suggested that the serum-derived hyaluronan associated protein
      (SHAP)-hyaluronan (HA) complex in the sera of patients with rheumatoid arthritis
      is useful as a marker that directly correlates with the degree of inflammation.
      Here, we have investigated the serum levels of the SHAP-HA complex in patients at
      various clinical stages of chronic hepatitis (CH), liver cirrhosis (LC), and
      hepatocellular carcinoma (HCC) caused by infection with the hepatitis C or
      hepatitis B virus. Both serum levels of the SHAP-HA complex and HA in those
      patients were significantly higher than those of the controls and increased in
      the order of CH<LC<HCC. Different from the HA levels, there was a significant
      difference in the SHAP-HA complex levels between the LC and HCC groups in both
      HBV- and HCV-infected patients. In addition, the serum level of the SHAP-HA
      complex correlated with the well-known biomarkers for liver injury and function
      such as albumin and platelet, including the HCC indicator alpha-fetoprotein. In
      conclusion, the present data suggest that the SHAP-HA complex level is a better
      indicator for the progression of the stages of liver fibrosis, and that it could
      be a marker for HCC, in both HBV- and HCV-infected patients.

PMID- 16448843
TI  - Intravenous methylprednisolone pulse therapy for children with autoimmune
      hepatitis.
AB  - OBJECTIVE: To estimate an efficacy of intravenous methylprednisolone pulse
      therapy (m-PSL) and the occurrence of corticosteroid-related side effects in
      children with autoimmune hepatitis (AIH), compared with oral corticosteroid
      therapy. STUDY DESIGN: The subjects consisted of nine children with AIH. Patients
      were divided into two groups. Group 1 was consisted of four patients who were
      treated with conventional oral prednisone therapy without m-PSL. Group 2 was
      consisted of five children who were treated with m-PSL as an induction therapy
      and maintained on oral prednisone. RESULTS: The median duration needed for
      normalization of alanine aminotransferase was 285 days (range 18-617 days) in
      group 1 and 54 days (range 15-116 days) in group 2. The most frequent side
      effects were obesity and growth retardation. The Z-score in group 1 tended to be
      lower than in group 2 and body mass index in group 1 tended to be higher than in
      group 2. CONCLUSION: The m-PSL may become a safe and effective therapy for
      children with AIH. Further study is needed to establish the appropriate therapy
      for AIH in children.

PMID- 16448844
TI  - Recombinant alphaviruses as vectors for anti-tumour and anti-microbial
      immunotherapy.
AB  - BACKGROUND: Vectors derived from alphaviruses are gaining interest for their high
      transfection potency and strong immunogenicity. OBJECTIVES: After a brief
      introduction on alphaviruses and their vectors, an overview is given on current
      preclinical immunotherapy studies using vector systems based on alphaviruses. The
      efficacy of alphavirus vectors in inducing immune responses will be illustrated
      by a more detailed description of immunization studies using recombinant Semliki
      Forest virus for the treatment of human papilloma virus-induced cervical cancer.
      RESULTS: Immunization with recombinant alphavirus results in the induction of
      humoral and cellular immune responses against microbes, infected cells and cancer
      cells. Preclinical studies demonstrate that infectious diseases and cancer can be
      treated prophylactically as well as therapeutically. CONCLUSIONS: Alphavirus
      based genetic immunization strategies are highly effective in animal model
      systems, comparing quite favourably with any other approach. Therefore, we hope
      and expect to see an efficient induction of tumour-or microbial immunity and a
      positive outcome in future clinical efficacy studies.

PMID- 16448845
TI  - Degradation of perilipin is mediated through ubiquitination-proteasome pathway.
AB  - Perilipin protein coats the surface of intracellular lipid droplets and plays
      fundamental roles in lipid droplet formation and triacylglycerol hydrolysis.
      Perilipin is transcriptionally regulated through peroxisome proliferator
      activated receptor and post-translationally stabilized by stored intracellular
      neutral lipids. In this study, we show that perilipin protein accumulates in
      transfected Chinese hamster ovary cells cultured in the presence of fatty acids
      but in turn is destabilized when lipid precursors for triacylglycerol synthesis
      are removed from culture serum. Adding fatty acids in the culture medium prevents
      the degradation of perilipin. Moreover, specific proteasome inhibitors, MG132,
      lactacystin, and ALLN, block the degradation, whereas inhibitors of other
      proteases are ineffective. Pulse-chase experiments confirm that perilipin is
      degraded through proteasome, a process that is inhibited by MG132 or ALLN and
      blunted by the addition of oleic acid. We have detected the co
      immunoprecipitation of perilipin and ubiquitin, thus confirming that perilipin is
      conjugated to poly-ubiquitin and targeted for proteasomal degradation. Treatment
      with MG132 increases the expression of perilipin associated with lipid droplets
      as well as modestly throughout the cytosol. We conclude that the degradation of
      perilipin is mediated through an ubiquitination-proteasome pathway, which
      suggests another mode for the post-translational regulation of perilipin.

PMID- 16448846
TI  - Transcallosal sensorimotor integration: effects of sensory input on cortical
      projections to the contralateral hand.
AB  - OBJECTIVE: Low amplitude vibration of forearm or hand muscles predominantly
      activates proprioceptive inputs that influence corticospinal projections in a
      focal manner, increasing output to the stimulated muscle while reducing output to
      neighbouring muscles. Modulation of contralateral forearm muscles by vibration
      has also been reported on one occasion. The aim of the current investigation was
      to investigate the effects of proprioceptive input from a hand muscle on
      corticospinal excitability, intracortical inhibition (SICI) and interhemispheric
      inhibition (IHI) targeting the homologous contralateral muscle. METHODS:
      Transcranial Magnetic Stimulation (TMS) was delivered to the left cortical hand
      area of 10 healthy subjects and surface electromyography (EMG) recordings taken
      from the right First Dorsal Interosseus (FDI) and Abductor Digiti Minimi (ADM).
      The effect of low amplitude vibration of the left FDI on MEP amplitudes, SICI and
      IHI targeting the right hand was assessed. RESULTS: Vibration of the left FDI
      caused a significant reduction in MEP amplitudes in the homologous right FDI but
      not in the right ADM. SICI and IHI targeting both muscles were also significantly
      increased. CONCLUSIONS: We conclude that proprioceptive input from a hand muscle
      reduces the corticospinal excitability of the contralateral homologous muscle.
      The increases in SICI and IHI suggest that at least some of this effect occurs in
      the cortex ipsilateral to the stimulus and this may be mediated via transcallosal
      fibres. SIGNIFICANCE: These results suggest that sensory input can modulate
      excitability in both motor cortices simultaneously, as well as the relationship
      between them. Interventions which modulate this transcallosal relationship may
      become useful in disorders where abnormal IHI is a potential therapeutic target.

PMID- 16448847
TI  - Interictal EEG as a physiological adaptation. Part II. Topographic variability of
      composition of brain oscillations in interictal EEG.
AB  - OBJECTIVE: In the present experimental study, we examined topographic variability
      of composition of brain oscillations and their temporal behavior in frequencies
      from 0.5 to 30 Hz of interictal EEG without epileptiform abnormalities and
      healthy EEG. METHODS: Spatio-temporal variability of brain oscillations (indexed
      by short-term EEG spectral patterns (SPs)) was assessed by the probability
      classification analysis of SPs. As a result, multi-dimensional SP-vector for each
      analysis EEG epoch was obtained. RESULTS: It was demonstrated that interictal EEG
      was characterized (a) by a significant decrease of spatio-temporal variability of
      brain oscillations, (b) by longer periods of temporal stabilization for
      operational modules which comprise larger number of cortical areas, and (c) by
      significantly more intermittent recurrence when compared with EEG of control
      subjects. Generally it was shown that EEG channels display different states of
      coordination independently on their correlation and coherence using brain
      oscillations at multiple frequencies. CONCLUSIONS: Results of this study
      suggested that EEG correlate of chronic epileptogenesis in the brain is a
      particular metastable state of biopotential field, which can be estimated by SP
      vector. The fact that all results were significantly different from surrogate
      EEGs reflects a nonoccasional and thus, most likely, an adaptive nature of spatio
      temporal reorganization in interictal EEG. SIGNIFICANCE: Parameters of spatio
      temporal organization of interictal EEG without the signs of epileptiform
      activity can be considered as additional information in premorbid diagnostics of
      status epilepticus, and may also provide insights into basic laws that govern
      brain oscillations in general.

PMID- 16448848
TI  - Mercury amalgam dental fillings: an epidemiologic assessment.
AB  - Dental amalgam fillings containing approximately 50% mercury have been used for
      almost 200 years and have been controversial for almost the same time.
      Allegations of effects caused by amalgams have involved many diseases. Recent
      evidence that small amounts of mercury are continuously released from amalgam
      fillings has fuelled the controversy. This is a comprehensive review of the
      epidemiologic evidence for the safety of dental amalgam fillings, with an
      emphasis on methodological issues and identifying gaps in the literature. Studies
      show little evidence of effects on general chronic disease incidence or
      mortality. Limited evidence exists for an association with multiple sclerosis,
      but few studies on either Alzheimer's or Parkinson's diseases. The preponderance
      of evidence suggests no renal effects and that ill-defined symptom complexes,
      including chronic fatigue syndrome, are not caused by amalgams. There is little
      direct evidence that can be used to assess reproductive hazards. Overall, few
      relevant epidemiologic studies are available. Most prior assessments of possible
      amalgam health effects have been based on comparisons of dental mercury exposures
      with occupational exposures causing harm. However, the amalgam-exposed population
      contains a broader, possibly more susceptible, spectrum of people. Common
      limitations of population-based studies of dental amalgam effects include
      inadequate longitudinal exposure assessment and negative confounding by better
      access to dental care in higher socioeconomic groups. Better designed studies are
      needed, particularly for investigation of neurodegenerative diseases and effects
      on infants and children.

PMID- 16448850
TI  - International forum--the "6 Pillars" of best practice in apheresis technologies:
      introductory remarks.

PMID- 16448855
TI  - Controversies in cardiology.

PMID- 16448856
TI  - Decline in seizure propensity in seizure-free patients as reflected in the
      evolution of the therapeutic antiepileptic drug threshold.
AB  - To better understand mechanisms of remission, the decline in seizure propensity
      in seizure-free patients was investigated. Plasma antiepileptic drug levels were
      measured in 199 adults seizure-free for 2 or more years, who consented to
      reduction and eventual discontinuation of therapy. Among 117 patients on
      monotherapy, drug dosage was reduced in 82 and therapy was terminated in 35. The
      initial therapeutic threshold was known in 51 cases, and the new threshold was
      determined in all cases of relapse. Four types of evolution were observed: no
      decline in seizure propensity; restricted decline and relapse; greater decline
      but relapse; and decline below the intrinsic seizure threshold (no relapse).
      Patients with seizure control immediately after onset of treatment were more
      likely to obtain remission. Our findings indicate that in seizure-free patients,
      seizure propensity only rarely remains unchanged, remission is attained by both
      qualitative and quantitative mechanisms, and there may be different mechanisms
      underlying quantitative declines in seizure propensity.

PMID- 16448857
TI  - Development of an enzyme-linked immunosorbent assay for vitellogenin of Morelet's
      crocodile (Crocodylus moreletii).
AB  - The purpose of this study was to develop an immunoassay for vitellogenin in
      Morelet's crocodile (Crocodylus moreletii). Blood was collected from wild-caught
      crocodiles in Belize. Plasma samples from adult females taken during the breeding
      season were used for vitellogenin purification and samples from adult males were
      used for comparison. No differences were detected between males and females for
      plasma total protein concentration, as measured by Coomassie assay. However,
      denaturing polyacrylamide gel electrophoresis (SDS-PAGE) revealed that female
      plasma contained a 210-kDa protein, presumably the vitellogenin monomer, that was
      absent in adult male plasma. The identity of the putative vitellogenin was
      confirmed by its cross-reactivity in Western blots with a vitellogenin antiserum
      that was generated against a conserved vitellogenin peptide sequence. Crocodile
      vitellogenin was purified by two successive rounds of DEAE chromatography. The
      purified protein had an apparent molecular mass of 450 kDa, as determined by gel
      filtration chromatography, and 210 kDa on SDS-PAGE. An indirect enzyme-linked
      immunosorbent assay (ELISA) was then developed for C. moreletii vitellogenin. The
      detection limit of the assay was 20.0 ng/mL. The intra- and inter-assay
      coefficients of variation were 5.3% and 9.8%, respectively. The recovery of
      vitellogenin diluted into male plasma was 94.7%. The ELISA assay revealed that
      vitellogenin levels of adult female plasma during the breeding season ranged from
      1.8 to 3.1 mg/mL with a mean of 2.5+/-0.25 mg/mL. No vitellogenin was detected in
      adult male plasma. Induction of vitellogenin in Morelet's crocodile may be a
      useful model system for field studies of crocodile reproduction and for
      investigations of endocrine disruption in this species.

PMID- 16448858
TI  - Possible mediators involved in decreasing peripheral vascular resistance with
      blackcurrant concentrate (BC) in hind-limb perfusion model of the rat.
AB  - We analyzed mechanisms decreasing hind-limb perfusion pressure (PP) with
      blackcurrant concentrate (BC) in the rat. The decrease in PP with BC was
      abolished by endothelial removal, nitroarginine plus tetraethylammonium,
      nitroarginine plus catalase or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one as an
      inhibitor of guanylyl cyclase and potassium channel(s), and accompanied by the
      increased cyclic GMP level. Partial but significant inhibition caused by KCl was
      observed during contraction. Authentic H2O2 decreased the PP in a sensitive
      manner to catalase and tetraethylammonium. The decrease in PP with BC in the
      presence of nitroarginine was significantly attenuated by diverse potassium
      channel blockers. Two delphinidins of 4 anthocyanins purified from BC definitely
      decreased the PP through similar mechanisms to BC. These results suggest that the
      decreased PP with BC is possibly mediated by endothelial NO and H2O2, and
      partially through the activation of diverse potassium channels, and that 2
      delphinidins play a major role as active components of BC.

PMID- 16448859
TI  - Role of NO and EDHF-mediated endothelial function in the porcine pulmonary
      circulation: comparison between pulmonary artery and vein.
AB  - OBJECTIVE: To compare electrophysiological measurement of nitric oxide (NO)
      release and endothelium-derived hyperpolarizing factor (EDHF)-mediated
      endothelial function in porcine pulmonary arteries and veins. METHODS: Isolated
      pulmonary interlobular arteries (PA) and veins (PV) were obtained from a local
      slaughterhouse. By using a NO-specific electrode and a conventional intracellular
      microelectrode, the amount of NO released from endothelial cells and
      hyperpolarization of smooth muscle cells were investigated. The bradykinin (BK)
      induced relaxation in the precontraction by U(46619) was examined in the absence
      or presence of N(G)-nitro-l-arginine (l-NNA), indomethacin (INDO) plus
      oxyhemoglobin (HbO). RESULTS: The basal release of NO was 7.0+/-1.2 nmol/L in PA
      (n=8) and 5.5+/-1.6 nmol/L in PV (n=8, p<0.01). BK-induced release of NO was
      160.4+/-10.3 nmol/L in PA (n=8) and 103.0+/-14.7 nmol/L in PV (n=8, p<0.001) with
      longer releasing duration in PA than in PV (14.3+/-1.3 vs. 12.1+/-0.8 min,
      p<0.01). BK evoked an endothelium-dependent hyperpolarization and relaxation that
      were reduced by l-NNA, INDO, and HbO (hyperpolarization: 12.8+/-1.3 vs. 8.0+/-1.4
      mV in PA, n=6, p<0.001 and 8.3+/-1.4 vs. 3.0+/-0.8 mV in PV, n=6, p<0.001;
      relaxation: 92.8+/-3.1% vs. 19.6+/-11.1% in PA n=8, p<0.001 and 70.3+/-7.9% vs.
      6.0+/-6.8% in PV, n=8, p<0.001). Both hyperpolarization (8.0+/-1.4 vs. 3.0+/-0.8
      mV, p<0.001) and relaxation (19.6+/-11.1% vs. 6.0+/-6.8%, p<0.01) were greater in
      PA than in PV. CONCLUSIONS: Both NO and EDHF play an important role in regulation
      of porcine pulmonary arterial and venous tones. The more significant role of NO
      and EDHF is revealed in pulmonary arteries than in veins.

PMID- 16448860
TI  - Embryonic expression of engrailed in sea urchins.
AB  - Neural patterning genes that are expressed along the anterior-posterior axis of
      deuterostomes are expressed late in larval development in echinoderms and are
      thought to function in establishing the highly-derived, adult body plan. We have
      used genomic resources to clone an engrailed gene (SpEn) from Strongylocentrotus
      purpuratus, and with this we have developed an antibody specific for SpEn. SpEn
      is expressed late in embryogenesis in the developing larval nervous system. At
      the prism stage, a small number of neuroblasts in the oral ectoderm on the edge
      of the larval mouth begin expressing SpEn. The cells are in bilaterally symmetric
      positions. The expression of SpEn precedes the expression of the neural markers,
      synaptotagmin and serotonin in the SpEn immunoreactive cells. The SpEn cells are
      located on the margin of the domain of cells expressing SpNK2.1, but they do not
      have nuclear SpNK2.1. Expression of engrailed in a pair of bilateral neural
      structures in early development appears to be a shared feature of bilaterians.

PMID- 16448861
TI  - Zebrafish BarH-like genes define discrete neural domains in the early embryo.
AB  - BarH (Barhl) genes encode for highly conserved homeodomain-containing
      transcription factors involved in critical functions during development,
      including cell fate specification, migration and survival. Here, we report the
      dynamic and restricted expression of three zebrafish barhl within the developing
      central nervous system. barhl2 becomes expressed in the late gastrula as a
      transverse diencephalic domain located immediately caudal to the prospective
      eyes. At early somitogenesis, barhl1.1 and barhl1.2 are expressed in the
      diencephalon in domains that partially overlap with the ventral and dorsal
      aspects of barhl2 expression, respectively. At later stages, expression of all
      zebrafish barhl shows large extent of overlap in the pretectum, tectum and dorsal
      hindbrain. The presence of a unique territory of barhl2 expression in the dorsal
      telencephalon and the high levels of expression in the retina are both consistent
      with expression reports of other Barhl2 orthologues, and support the subdivision
      of vertebrate Barhl into two paralogue groups based on the phylogenetic analysis
      of nucleotide and amino acid sequences.

PMID- 16448862
TI  - Characterization of retinoid-X receptor genes rxra, rxrba, rxrbb and rxrg during
      zebrafish development.
AB  - During development of vertebrate embryos, retinoic acid plays a variety of roles
      that are mediated by binding to retinoic acid receptors (Rars) and their
      heterodimerization partners, the retinoid receptors (Rxrs). Here, we characterize
      the expression patterns of four zebrafish rxr genes during development and
      provide an analysis of the phylogenetic relationships between zebrafish and
      tetrapod Rxr genes based on sequence similarities and conserved syntenies. This
      analysis prompted the renaming of several of the zebrafish rxr genes to match
      their tetrapod orthologs. Understanding phylogenetic relationships among Rxr
      genes and their expression patterns during development provides a foundation for
      future studies of Rxr functions.

PMID- 16448863
TI  - Cloning and developmental expression of WSTF during Xenopus laevis embryogenesis.
AB  - The gene WSTF is deleted in the autosomal dominant hereditary disorder Williams
      Beuren syndrome. This disorder is caused by a 1.3 megabase deletion in human
      chromosome 7, encompassing at least 17 genes. The WSTF protein contains a
      bromodomain, found predominantly in chromatin-associated proteins. Reported
      association of WSTF with chromatin remodeling factors and functional data support
      a role for WSTF during chromatin remodeling. Here, we report the cloning and
      developmental expression pattern of Xenopus laevis WSTF. Xenopus laevis WSTF is a
      protein with a predicted amino acid sequence of 1441 amino acids. Three discrete
      domains can be identified in the Xenopus laevis WSTF protein, a PHD finger, a DDT
      domain and a bromodomain. Alignment of Xenopus WSTF with the corresponding
      orthologues from Homo sapiens, Gallus gallus, Mus musculus and Danio rerio
      demonstrates an evolutionary conservation of WSTF amino acid sequence and domain
      organization. In situ hybridization reveals a dynamic expression profile during
      embryonic development. WSTF is expressed differentially in neural tissue,
      especially during neurulae stages in the eye, in neural crest cells and the
      brain.

PMID- 16448864
TI  - Segregation--the perspectives of young patients and their parents.
AB  - BACKGROUND: Segregation is used increasingly to prevent cross infection, yet
      little is known about service users' views regarding segregation and its
      perceived impact. The aim of this study was to elicit patients and carers' views
      and to involve them in the process of introducing segregation in a paediatric CF
      centre. METHOD: Open-ended questionnaires were posted to all parents (n=192) and
      to patients over 10 years (n=101). A content analysis identified common themes.
      Inter-rater agreement about themes was high (83%). RESULTS: Parents (91%) and
      children (92%) supported segregated treatment. Parents appeared to be aware of
      the positive and negative aspects of segregation, and to engage in a balancing
      act that led them to conclude that segregation was a 'necessary evil'. Children
      appeared to be less analytical and were concerned mostly with boredom and
      isolation. Age, level of maturity, and hospital experience were perceived to be
      determinants of patient adaptation to segregation. CONCLUSION: Segregation has
      considerable emotional, social, and practical implications for patients and
      families. Obtaining users' views increased our understanding of the psychosocial
      consequences of segregation and facilitated its implementation.

PMID- 16448865
TI  - What makes a champion? Explaining variation in human athletic performance.
AB  - Variation in human athletic performance is determined by a complex interaction of
      socio-cultural, psychological, and proximate physiological factors. Human
      physiological trait variance has both an environmental and genetic basis,
      although the classic gene-environment dichotomy is clearly too simplistic to
      understand the full range of variation for most proximate determinants of
      athletic performance, e.g., body composition. In other words, gene and
      environment interact, not just over the short term, but also over the lifetime of
      an individual with permanent effects on the adult phenotype. To further
      complicate matters, gene and environment may also be correlated. That is,
      genetically gifted individuals may be identified as children and begin training
      pulmonary, cardiovascular, and muscle systems at an early critical age. This
      review covers evidence in support of a genetic basis to human athletic
      performance, with some emphasis on the recent explosion of candidate gene
      studies. In addition, the review covers environmental influences on athletic
      performance with an emphasis on irreversible environmental effects, i.e.,
      developmental effects that may accrue during critical periods of development
      either before conception (epigenetic effects), during fetal life (fetal
      programming), or during childhood and adolescence. Throughout, we emphasize the
      importance of gene-environment interaction (G x E) as a means of understanding
      variation in human physiological performance and we promote studies that
      integrate genomics with developmental biology.

PMID- 16448866
TI  - Decoding 2D-PAGE complex maps: relevance to proteomics.
AB  - This review describes two mathematical approaches useful for decoding the complex
      signal of 2D-PAGE maps of protein mixtures. These methods are helpful for
      interpreting the large amount of data of each 2D-PAGE map by extracting all the
      analytical information hidden therein by spot overlapping. Here the basic theory
      and application to 2D-PAGE maps are reviewed: the means for extracting
      information from the experimental data and their relevance to proteomics are
      discussed. One method is based on the quantitative theory of statistical model of
      peak overlapping (SMO) using the spot experimental data (intensity and spatial
      coordinates). The second method is based on the study of the 2D-autocovariance
      function (2D-ACVF) computed on the experimental digitised map. They are two
      independent methods that are able to extract equal and complementary information
      from the 2D-PAGE map. Both methods permit to obtain fundamental information on
      the sample complexity and the separation performance and to single out ordered
      patterns present in spot positions: the availability of two independent
      procedures to compute the same separation parameters is a powerful tool to
      estimate the reliability of the obtained results. The SMO procedure is an unique
      tool to quantitatively estimate the degree of spot overlapping present in the
      map, while the 2D-ACVF method is particularly powerful in simply singling out the
      presence of order in the spot position from the complexity of the whole 2D map,
      i.e., spot trains. The procedures were validated by extensive numerical
      computation on computer-generated maps describing experimental 2D-PAGE gels of
      protein mixtures. Their applicability to real samples was tested on reference
      maps obtained from literature sources. The review describes the most relevant
      information for proteomics: sample complexity, separation performance,
      overlapping extent, identification of spot trains related to post-translational
      modifications (PTMs).

PMID- 16448867
TI  - A rapid high performance liquid chromatographic determination of methyldopa in
      human serum with fluorescence detection and alumina extraction: application to a
      bioequivalence study.
AB  - A simple and ultra rapid high performance liquid chromatographic (HPLC) method
      coupled with alumina extraction and fluorescence detection was described for
      determination of methyldopa in human serum. The drug and an internal standard
      were adsorbed onto alumina and eluted using acidic methanol. The eluate was
      directly injected onto ODS reverse phase column using a mixture of phosphate
      buffer (0.05 M) containing triethylamine (100 microl/l, v/v; pH 2.3) and methanol
      (92:8, v/v) at a flow rate of 2.1 ml/min as the mobile phase. The fluorescence
      detector excitation and emission wavelengths were set at 270 and 320 nm,
      respectively. No interference in the assay from any endogenous substances or
      other concurrently used drugs was observed and the retention times of I.S. and
      the drug were 1.7 and 2.4 min, respectively with total run time (injection to
      injection) of less than 3.5 min. The limit of quantification was evaluated to be
      2 ng/ml. Validity of the method was studied and the method was precise and
      accurate with a linearity range from 20 ng/ml to 5000 ng/ml. This method has been
      used in a randomized crossover bioequivalence study of two different methyldopa
      preparations in 24 healthy volunteers.

PMID- 16448868
TI  - Conformational fluctuations of proteins revealed by variable pressure NMR.
AB  - With the high-resolution variable-pressure NMR spectroscopy, one can study
      conformational fluctuations of proteins in a much wider conformational space than
      hitherto explored by NMR and other spectroscopic techniques. This is because a
      protein in solution generally exists as a dynamic mixture of conformers mutually
      differing in partial molar volume, and pressure can select the population of a
      conformer according to its relative volume. In this review, we describe how
      variable-pressure NMR can be used to probe conformational fluctuations of
      proteins in a wide conformational space from the folded to the fully unfolded
      structures, with actual examples. Furthermore, the newly emerging technique "NMR
      snapshots" expresses amply fluctuating protein structures as changes in atomic
      coordinates. Finally, the concept of conformational fluctuation is extended to
      include intermolecular association leading to amyloidosis.

PMID- 16448869
TI  - Biochemical characterization and preliminary X-ray crystallographic study of the
      domains of human ZBP1 bound to left-handed Z-DNA.
AB  - ZBP1 is involved in host responses against cellular stresses, including
      tumorigenesis and viral infection. Structurally, it harbors two copies of the
      Zalpha domain containing the Zalpha motif, at its N terminus. Here, we attempted
      to characterize the Z-DNA binding activities of two Zalpha domains in the human
      ZBP1, hZalpha(ZBP1) and hZbeta(ZBP1), using circular dichroism (CD). Our results
      indicated that both hZalpha(ZBP1) and hZbeta(ZBP1) are viable Z-DNA binders, and
      their binding activities are comparable to those of previously-established Zalpha
      domains. Additionally, we crystallized hZbeta(ZBP1) in a complex with Z-DNA,
      d(TCGCGCG)2. The crystal diffracted to 1.45 angstroms, and belongs to the
      P2(1)2(1)2(1) space group, with the unit-cell parameters: a = 29.53 angstroms, b
      = 58.25 angstroms, and c = 88.61 angstroms. The delineation of this structure
      will provide insight into the manner in which diverse Zalpha motifs recognize Z
      DNA.

PMID- 16448870
TI  - Casein kinases phosphorylate multiple residues spanning the entire hnRNP K
      length.
AB  - Heterogeneous Nuclear Ribonucleoprotein K (hnRNP K) is an RNA/DNA-binding protein
      involved in many processes that regulate gene expression. K protein's pleiotropic
      action reflects the diversity of its molecular interactions. Many of these
      interactions have been shown to be regulated by phosphorylation. K protein
      contains more than seventy potential phosphorylation sites. We used an integrated
      approach of mass spectrometry and computer analysis to explore patterns of K
      protein phosphorylation. We found that in vitro a single kinase can phosphorylate
      K protein on multiple sites spanning the entire length of the protein, including
      residues contained within the RNA/DNA-binding domains. 2-D gel electrophoresis of
      K protein purified from cells identified 5-8 spots. Mass spectrometry of K
      protein isolated from proliferating cells and from cells under oxidative stress
      revealed the same pattern of phosphopeptides. The structural implications of
      phosphorylation are discussed.

PMID- 16448872
TI  - Strategies for the prevention and treatment of osteoporosis during early
      postmenopause.
AB  - During the perimenopause, both the quantity and quality of bone decline rapidly,
      resulting in a dramatic increase in the risk of fracture in postmenopausal women.
      Although many factors are known to be associated with osteoporotic fractures,
      measures to identify and treat women at risk are underused in clinical practice.
      Consequently, osteoporosis is frequently not detected until a fracture occurs.
      Identification of postmenopausal women at high risk of fracture therefore is a
      priority and is especially important for women in early postmenopause who can
      benefit from early intervention to maintain or to increase bone mass and, thus,
      reduce the risk of fracture. Most authorities recommend risk-factor assessment
      for all postmenopausal women, followed by bone mineral density measurements for
      women at highest risk (ie, all women aged > or =65 years, postmenopausal women
      aged <65 years with > or =1 additional risk factors for osteoporosis, and
      postmenopausal women with fragility fractures). All postmenopausal women can
      benefit from nonpharmacologic interventions to reduce the risk of fracture,
      including a balanced diet with adequate intake of calcium and vitamin D, regular
      exercise, measures to prevent falls or to minimize their impact, smoking
      cessation, and moderation of alcohol intake. Several pharmacologic agents,
      including the bisphosphonates (eg, alendronate, risedronate, and ibandronate) and
      the selective estrogen receptor modulator, raloxifene, have been shown to
      increase bone mass, to reduce fracture risk, and to have acceptable side-effect
      profiles. Women who have discontinued hormone therapy are in particular need of
      monitoring for fracture risk, in light of the accelerated bone loss and increased
      risk of fracture that occurs after withdrawal of estrogen treatment.

PMID- 16448873
TI  - Epidemiology, etiology, and diagnosis of osteoporosis.
AB  - Osteoporosis, a major public health problem, is becoming increasingly prevalent
      with the aging of the world population. Osteoporosis is a skeletal disorder
      characterized by compromised bone strength, which predisposes the individual to
      an increased risk of fractures of the hip, spine, and other skeletal sites. The
      clinical consequences and economic burden of this disease call for measures to
      assess individuals who are at high risk to allow for appropriate intervention.
      Many risk factors are associated with osteoporotic fracture, including low peak
      bone mass, hormonal factors, the use of certain drugs (eg, glucocorticoids),
      cigarette smoking, low physical activity, low intake of calcium and vitamin D,
      race, small body size, and a personal or a family history of fracture. All of
      these factors should be taken into account when assessing the risk of fracture
      and determining whether further treatment is required. Because osteoporotic
      fracture risk is higher in older women than in older men, all postmenopausal
      women should be evaluated for signs of osteoporosis during routine physical
      examinations. Radiologic laboratory assessments of bone mineral density generally
      should be reserved for patients at highest risk, including all women over the age
      of 65, younger postmenopausal women with risk factors, and all postmenopausal
      women with a history of fractures. The evaluation of biochemical markers of bone
      turnover has been useful in clinical research. However, the predictive factor of
      these measurements is not defined clearly, and these findings should not be used
      as a replacement for bone density testing. Together, clinical assessment of
      osteoporotic risk factors and objective measures of bone mineral density can help
      to identify patients who will benefit from intervention and, thus, can
      potentially reduce the morbidity and mortality associated with osteoporosis
      associated fractures in this population.

PMID- 16448875
TI  - Headache.
AB  - The patient who presents with headache can be diagnosed quickly and efficiently
      once the correct pattern has been identified. Most patients will have migraine,
      and treatment is based on the severity and disability. If the identified patient
      has significant disability, a medication that treats comorbidity should be
      prescribed. Patients who have a serious underlying disorder can be recognized by
      a thoughtful history and careful examination and can be worked up accordingly.
      Patients who have an acute new onset headache problem that requires immediate
      attention can be triaged and treated once their pattern and history are clear.
      Hopefully, increasing comfort levels with diagnosing headaches will allow the
      primary care practitioner to treat headache patients more effectively and
      efficiently.

PMID- 16448876
TI  - Diagnosis and management of dizziness and vertigo.
AB  - Dizziness and vertigo present in patients of all ages. Particularly in older
      patients, dizziness is associated with a variety of cardiovascular, neurosensory,
      and psychiatric conditions and with the use of multiple medications. For the
      patient, the symptoms can be debilitating. In patients older than 60 years, 20%
      have experienced dizziness severe enough to affect their daily activities.
      Appropriate diagnosis and treatment can significantly improve quality of life.
      Most causes of dizziness are benign, but early recognition of serious or life
      threatening disease is important. Management of these patients includes referral
      for neuroimaging and further evaluation in an emergency department.

PMID- 16448877
TI  - Approach to ophthalmologic emergencies.
AB  - This article presents evaluation and treatment approaches to ophthalmologic
      conditions that are likely to be encountered in a primary care office. These
      conditions can be organized by diagnostic category, symptoms, and location of
      complaint. By using one ora combination of these categories, the practitioner can
      provide appropriate, timely, and effective ophthalmologic evaluation and
      treatment. Acute conditions are categorized according to urgency of intervention.

PMID- 16448878
TI  - Otolaryngologic emergencies in the outpatient setting.
AB  - Disease processes involving the ear, nose, and throat account for millions of
      office visits to primary care physicians per year. Because of their proximity to
      the airway as well as critical neurologic and vascular structures, the disease
      process in each individual case carries the potential for significant
      complications. Fortunately, improvements in medical care have significantly
      reduced the prevalence of these complications. As a result of their relative
      rarity, most physicians may be unfamiliar with the clinical presentation of these
      entities. This article familiarizes the physician with the pathophysiology and
      clinical presentation of the more commonly encountered otolaryngologic
      complications. The physician should seek to rule out the presence of the
      aforementioned complications in each patient who presents with an otolaryngologic
      complaint. Any suggestion of their presence should prompt an immediate referral
      to a subspecialist or an emergency department. It is hoped that continued
      familiarization with these' disease processes will maintain them as rare entities
      of medical practice.

PMID- 16448879
TI  - Orthopedic trauma: office management of major joint injury.
AB  - Orthopedic injuries are common reasons for visits to primary care physicians.
      Careful history and physical examination with intelligent use of imaging
      technology will arrive at the correct diagnosis in most patients. Many conditions
      may be definitively managed by the office internist. Others maybe initially
      stabilized and referred to orthopedic surgeons for definitive care. Nondisplaced
      fractures, tendon injuries, sprains, and overuse syndromes are entities within
      the purview of the primary care physician. Familiarity and confidence with
      diagnosis and management of these conditions in the office is optimal for the
      care of the adult patient.

PMID- 16448880
TI  - Reduced expression of endothelial connexins 43 and 37 in hypertensive rats is
      rectified after 7-day carvedilol treatment.
AB  - BACKGROUND: The aim of this study was to clarify the response of endothelial
      connexins to hypertension and antihypertensive drugs. METHODS: Rats remained
      normotensive (group 1, N = 10) or were made hypertensive using N(omega)-nitro-L
      arginine methyl ester (L-NAME) (groups 2 to 4, N = 10/group). Seven weeks later
      groups 3 and 4 were respectively fed atenolol or carvedilol daily for 7 days and
      the aortic endothelial gap junctions were analyzed. In parallel the effects of
      atenolol, carvedilol, labetalol, vitamin C, and vitamin E on connexin43 (Cx43) in
      human umbilical vein endothelial cells (HUVEC) were compared. RESULTS:
      Endothelial Cx43 was reduced by 35% and Cx37 by 59% in hypertensive rats (P <
      .001). The reduction was recovered fully by carvedilol but only partially by
      atenolol (P < .05), although both drugs lowered the blood pressure to similar
      levels. Cx40 remained stationary in all groups. In HUVEC, carvedilol (10
      microg/mL) increased Cx43 protein expression by >70% (P < .01), whereas other
      drugs had minimal effects. The upregulation by carvedilol was associated with
      increased transcripts and decreased proteolysis of Cx43. CONCLUSIONS: The study
      showed that L-NAME-induced hypertension has differential effects on endothelial
      connexins, which respond variously to carvedilol and atenolol. In HUVEC
      carvedilol directly upregulates endothelial Cx43 and the effect is independent of
      its antioxidant activity.

PMID- 16448881
TI  - The effect of alcohol and gender on ambulatory blood pressure: results from the
      Baseline Double Exposure study.
AB  - BACKGROUND: Research has demonstrated that psychosocial and lifestyle factors are
      associated with sustained increases in blood pressure (BP). METHODS: Using post
      hoc analyses from the Baseline Double Exposure cohort study, alcohol consumption
      and gender were examined as to their association with ambulatory BP (ABP) in
      participants with normal or elevated and untreated BP. RESULTS: The current study
      included 248 subjects, 135 (54.4%) of whom were women, with a mean age (+/- SD)
      of 50.8 +/- 6.6 years. The main effects model, which included BMI, multiple
      regression analysis with 24 h systolic BP as the dependent variable found that
      alcohol consumption (P = .033), male gender (P = .004), and age (P = .039) were
      significant variables associated with higher systolic BP, whereas exercise (P =
      .037) was associated with lower systolic BP. From the regression analysis, the
      independent effect of alcohol consumption (> or = 10 drinks per week) on systolic
      BP was 4.4 mm Hg for all subjects during 24 h and 7.1 mm Hg during spousal
      contact, whereas in women with this degree of alcohol consumption the effect on
      systolic BP was 8.4 mm Hg during 24 h and 11.4 mm Hg during spousal contact. When
      the interaction term of gender by drinking status was added to the same
      regression model, the term was not significant for systolic BP during 24 h, but
      was significant during spousal contact time (P = .047). CONCLUSIONS: The current
      study demonstrates an association between alcohol with higher systolic BP, more
      pronounced in women than men, particularly during spousal contact time. This is
      the first time that the interaction of alcohol and gender with ABP has been
      demonstrated.

PMID- 16448882
TI  - Longitudinal study on hypertension control in primary care: the Insubria study.
AB  - BACKGROUND: Hypertension control is still unsatisfactory. The study was aimed to
      evaluate blood pressure (BP) control rate and the impact of training general
      practitioners (GPs) about hypertension 1999 World Health
      Organization/International Society of Hypertension guidelines. METHODS: After a
      training session on the hypertension guidelines, 588 GPs consecutively enrolled
      5524 known hypertensive patients. During the first and follow-up visits (after 3,
      6, and 9 months) GPs recorded BP, lifestyle habits, and drug therapy. RESULTS:
      The BP was controlled in 33.4%, with systolic BP less controlled than diastolic
      BP. The BP control rate decreased (P < .001) from low to very high cardiovascular
      risk group and from lean to overweight and obese subjects. At the first visit
      97.3% of the patients were already on drug treatment: 40.3% with 1 drug, 38.9%
      with 2 drugs, 17.2% with 3 drugs and 3.6% with 4 or 5 drugs. The adherence to
      correct dietary and lifestyle habits was low. The drugs most often used were the
      angiotensin-converting enzyme inhibitors (3009 patients, 56%). During follow-up
      body weight and BP decreased; 1 or more drugs were added in 17.8% and the
      adherence to healthier lifestyle habits significantly increased. At the end of
      the survey BP control rate was significantly improved (52.7%). CONCLUSIONS: In
      primary care the hypertension control rate was still unsatisfactory, and our data
      suggest that it may be due to a not aggressive enough drug treatment and a low
      adherence to recommended lifestyle and dietary habits. Increasing the knowledge
      of GPs about guidelines was associated with an improvement of hypertension
      control rate.

PMID- 16448883
TI  - Control of high blood pressure in primary health care.

PMID- 16448884
TI  - Effect of terminal digit preference on blood pressure measurement and treatment
      in primary care.
AB  - BACKGROUND: Terminal digit preference in blood pressure (BP) measurement has been
      reported in both clinical and research settings. This article examines the
      prevalence of terminal digit preference (TDP) in primary care practices and the
      effect that a practice's level of TDP influences patients' BP measurements and
      management. METHODS: Data were obtained in cross-sectional fashion from the
      electronic medical records of active patients from 85 practices around the United
      States. The TDP prevalence was calculated, and statistical techniques were used
      to examine the influence of a practice's TDP on patients' BP measurements and on
      the likelihood that patients had an active prescription for selected
      antihypertensive medications. RESULTS: The TDP was common, with zero being
      recorded 44.6% and 47.5% of the time for systolic BP and diastolic BP,
      respectively. Patients belonging to practices with higher TDP levels had
      significantly (P < .01) lower systolic BP measurements than patients in practices
      with lower TDP levels. Patients belonging to practices with higher TDP levels
      also had significantly lower odds (odds ratio [OR] = 0.92, 95% confidence
      interval [CI] [0.85, 0.99], P = .036) of having an active prescription for an
      antihypertensive medication, an association that was stronger in women (OR =
      0.91, P = .023) than in men (OR = 0.95, P = .21). CONCLUSIONS: The TDP for BP
      measurements is common. Although TDP effects on patients' BP measurements may
      appear modest, treatment of patients, especially women, with antihypertensive
      medication may be systematically affected by this preference.

PMID- 16448885
TI  - Aortic depressor nerve myelinated fibers in acute and chronic experimental
      diabetes.
AB  - BACKGROUND: Preliminary data from our laboratory have demonstrated baroreflex
      dysfunction as early as 5 days after the onset of experimental diabetes in rats.
      The aim of the present study was to determine the morphologic alterations of the
      aortic depressor nerve of rats submitted to acute (15 days) or chronic (12 weeks)
      experimental diabetes. METHODS: Wistar rats received a single intravenous
      injection of streptozotocin (50 mg/kg) 15 days or 12 weeks before the
      experiments. Time control animals received vehicle. Under pentobarbital
      anesthesia the aortic depressor nerves were identified by means of
      electroneurographic recording simultaneously with the recording of arterial
      pressure. After identification, the aortic depressor nerves were prepared for
      light microscopy and our analysis only included the myelinated fibers. RESULTS:
      Five of 10 aortic depressor nerves from animals with acute diabetes showed clear
      signs of axonal atrophy with significantly smaller average diameter of myelinated
      fibers (1.9 +/- 0.1 microm) and their axons (1.0 +/- 0.1 microm) than the time
      control (2.1 +/- 0.1 microm and 1.2 +/- 0.1 microm, respectively). Histograms of
      the G-ratio (ratio between axon diameter and total fiber diameter--an index of
      axonal atrophy) distribution of acute diabetic animal nerves were shifted to the
      left. All aortic depressor nerves from animals with chronic diabetes showed signs
      of axonal atrophy with the average diameter of myelinated fibers (2.3 +/- 0.1
      microm) and their axons (1.2 +/- 0.1 microm) also being significantly smaller
      than the time control (2.6 +/- 0.2 microm and 1.5 +/- 0.1 microm, respectively).
      CONCLUSIONS: These findings provide morphologic support for an impaired
      baroreflex during acute and chronic experimental diabetes.

PMID- 16448886
TI  - Determinants of sustained uncontrolled blood pressure in a national cohort of
      persons with diabetes.
AB  - BACKGROUND: Randomized clinical trials have demonstrated that strict blood
      pressure (BP) control in diabetes reduces cardiovascular morbidity and mortality.
      Previous observational studies have confirmed that hypertension is inadequately
      controlled in the general population of the United States. In this study we
      evaluated the prevalence and determinants of severe, sustained, uncontrolled
      hypertension in a national cohort of persons with diabetes. METHODS: We
      identified 64,105 veterans from the national Veterans Administration diabetes
      registry for whom BP, survey, laboratory, and medication data were available.
      Using mean BP from three visits in fiscal year 2000, we determined the prevalence
      of sustained BP readings > or = 160/100, > or = 140/90, or > or = 130/80 mm Hg.
      We determined predictors of the three thresholds using demographic variables,
      self-reported medical comorbidities, estimated glomerular filtration rate, and
      number of BP-lowering medications. RESULTS: Over a mean interval of 131.0 days
      (+/-81.4), we found that 6,347 (9.9%) of the 64,105 veterans with diabetes had
      mean BP > or = 160/100 mm Hg. Similarly 25,924 (40.4%) had a mean BP > or =
      140/90 mm Hg, and 38,296 (59.7%) had a mean BP > or = 130/80 mm Hg. Independent
      predictors of mean BP > or = 160/100 mm Hg included age, ethnicity, education
      level, cardiovascular comorbidities, alcohol use, and number of BP-lowering
      medications. CONCLUSIONS: Administrative databases can be used to identify
      patients with sustained uncontrolled hypertension within health care systems. Our
      findings suggest important patient-level factors that can be targeted for quality
      improvement programs in diabetes.

PMID- 16448887
TI  - Twenty-four-hour heart rate and blood pressure are additive markers of left
      ventricular mass in hypertensive subjects.
AB  - BACKGROUND: We investigated whether mean heart rate (HR(24)) and blood pressure
      (BP) parameters during 24-h ambulatory BP monitoring (ABP) are independent or
      additive markers of left ventricular (LV) mass in subjects with newly diagnosed,
      untreated hypertension. METHODS: A total of 250 patients (40% women, 60% men;
      mean age 59.6 +/- 11 years) with essential hypertension who were attending the
      outpatient Hypertension Unit were studied. All patients underwent 24-h ABP and HR
      monitoring as well as echocardiography for assessment of left ventricular (LV)
      dimensions and function. RESULTS: A decreasing HR24 or increasing ABP parameters
      (ie, systolic, diastolic, mean BP, and pulse pressure) were associated with
      increasing LV mass (P < .001) and wall thickness (P < .01). In multivariate
      analysis, after adjusting for age, gender, body surface area, body mass index,
      hematocrit, glucose, cholesterol, smoking, and each of the measured ABP
      parameters separately, decreasing HR24 was independently related to increasing LV
      mass in addition to ABP and body size parameters (P < .001). The addition of HR24
      in different multivariate models for prediction of LV mass significantly
      increased the adjusted model r2 (range of r2 change: 0.039 to 0.064, P for change
      <.05). Decreasing HR24 or HR during daytime (6 am to 10 pm) was associated with a
      higher likelihood of LV hypertrophy in addition to ABP parameters (adjusted odds
      ratio 0.92 (CI 0.87 to 0.98), per 1 beat/min greater HR24 P = .002 and 0.93 (CI:
      0.87 to 0.98), per 1 beat/min greater HR in the daytime P = .017). CONCLUSION:
      The 24-h HR and BP during ABP are independent and additive markers of increased
      LV mass in untreated hypertensive individuals.

PMID- 16448888
TI  - Twenty-four-hour mean heart rate and likelihood of left ventricular hypertrophy.

PMID- 16448889
TI  - The relation of blood pressure to coronary heart mortality in different age
      groups varies by ethnicity.
AB  - BACKGROUND: The relative importance of pulse pressure, mean arterial pressure,
      systolic blood pressure (SBP), and diastolic blood pressure (DBP) as predictors
      of coronary heart disease (CHD) have been shown to change with aging in
      individuals of white ethnicity, but few published data exist for those of African
      American ethnicity. METHODS: To assess the role of ethnicity in this relationship
      we compared the association of BP indices to CHD mortality (from a pooled
      database of eight prospective cohorts, n = 29829, follow-up 13.8 +/- 7.9 years,
      1912 events) in the four age groups (30 to 39, 40 to 49, 50 to 59, and > or = 60
      years) by the decrease in the -2 log likelihood in Cox regression analyses of
      subjects who were not receiving antihypertensive drug therapy at baseline.
      RESULTS: All BP indices were significant (P < .05) for all age groups in models
      containing a single BP index. In white subjects, the best predictor of CHD
      mortality was DBP for persons 30 to 39 years of age, whereas SBP was the best
      predictor for persons 40 to 49, 50 to 59 and > or = 60 years of age. In African
      American subjects, SBP was the best predictor in all age groups. When considered
      jointly, DBP, but not SBP, was significantly associated with CHD mortality in
      white subjects 30 to 39 years of age. Only SBP was significant in white subjects
      40 to 49, 50 to 59, and > or = 60 years of age. In African Americans, SBP, but
      not DBP, was associated with CHD mortality in all four age groups when both were
      in the model. CONCLUSION: In African American subjects, SBP was found to be a
      better predictor of CHD mortality than DBP or pulse pressure. In white subjects,
      there was a shift in importance from DBP to SBP as predictors of CHD mortality
      from the 30 to 39-year age group to the older groups.

PMID- 16448890
TI  - Caffeine attenuates early post-exercise hypotension in middle-aged subjects.
AB  - BACKGROUND: Sustained hypotension after an acute dynamic exercise bout is due
      primarily to peripheral vasodilation. We tested the hypothesis that adenosine
      mediated vasodilation contributes to hypotension after exercise, by determining
      the effect of blocking its actions with caffeine. METHODS: Fourteen healthy
      middle-aged subjects (mean age = 51 +/- 3 years), cycled to peak effort on 2
      study days, after a randomized double-blind intravenous infusion of caffeine (4
      mg/kg) selective for adenosine receptor blockade, or vehicle. Both studies were
      performed after 72 h of caffeine abstinence. RESULTS: Infusion achieved 52.0 +/-
      6.1 mumol/L caffeine in plasma. Significant reductions in mean and diastolic
      blood pressure (BP) were elicited by prior exercise on the vehicle day (from 93
      +/- 2 to 85 +/- 2 mm Hg v from 79 +/- 2 to 73 +/- 3 mm Hg, respectively; both P <
      .05), but not after caffeine infusion. Systolic and mean BP, 10 min after
      exercise, were higher on the caffeine than on the vehicle day (by 9 +/- 3 and 6
      +/- 2 mm Hg, respectively; P < .05), as was heart rate (HR) (100 +/- 5 v 93 +/- 4
      beats/min; P < .05). CONCLUSIONS: These data suggest that endogenous adenosine
      contributes to early hypotension after exercise in healthy middle-aged subjects
      and underscore the importance of caffeine abstinence if BP or HR immediately
      after exercise is used to infer cardiovascular risk.

PMID- 16448891
TI  - Prehypertension is associated with insulin resistance state and not with an
      initial renal function impairment. A Metabolic Syndrome in Active Subjects in
      Spain (MESYAS) Registry substudy.
AB  - BACKGROUND: The aim of this study was to assess the prevalence of metabolic
      syndrome (MS) and other surrogate markers of insulin resistance, and whether
      these markers are better for defining the prehypertensive state than is renal
      dysfunction. METHODS: Data from 19,041 healthy active workers, mean age 42.2
      (10.7) years, from three health insurance companies, were prospectively
      collected. Presence of MS, assessed according to the modified criteria of the
      National Cholesterol Education Program Third Adult Treatment Panel, and the ratio
      of triglycerides to high-density lipoprotein were considered as surrogate markers
      of insulin resistance. Renal function was assessed by the Modification of Diet in
      Renal Disease Study equation. Blood pressure was classified as normotension (NT),
      prehypertension (PHT), or hypertension (HT) according to the guidelines of the
      seventh report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure. RESULTS: The global presence of
      MS was 11.8% The higher prevalence was found in subjects with hypertension (30%),
      followed by those with PHT (9.6%). The prevalence in normotensive subjects was
      very low (0.9%). The presence of MS and hypertension increased in parallel with
      age. Metabolic syndrome (odds ratio [OR] 4.3), obesity (OR 2.2), overweight (OR
      1.7), impaired fasting glucose (OR 1.3), and elevated triglycerides to HDL ratio
      (OR 1.2), but no degree of renal dysfunction, were independent risk factors for
      the progression from NT to PHT. CONCLUSIONS: Prehypertension is associated with
      markers of insulin resistance, assessed by the presence of MS and other surrogate
      markers, and not with an initial renal dysfunction. In this study, MS was found
      to be present in almost one third of hypertensive but asymptomatic and otherwise
      healthy workers.

PMID- 16448893
TI  - Metabolic syndrome and morphofunctional characteristics of the left ventricle in
      clinically hypertensive nondiabetic subjects.
AB  - BACKGROUND: The study was aimed to evaluate the impact of the metabolic syndrome
      on left ventricular (LV) structure and function in nondiabetic patients, never
      treated with antihypertensive or lipid-lowering drugs. METHODS: Eighty-eight
      patients, with recent finding of clinic BP >140 or 90 mm Hg, underwent 24-h blood
      pressure (BP) monitoring, echocardiogram, evaluation for metabolic syndrome
      (Adult Treatment Panel III criteria). RESULTS: Metabolic syndrome was diagnosed
      in 38 subjects (43.2%) (metabolic syndrome+). Age, gender, 24-h systolic and
      diastolic BP were similar between metabolic syndrome+ and metabolic syndrome-
      groups, whereas body mass index, clinic and 24-h heart rate, fasting glycemia,
      and triglycerides were significantly higher and HDL-cholesterol lower in
      metabolic syndrome + subjects. The prevalence of sustained hypertension (24-h BP
      >125 or 80 mm Hg) was similar between the two groups. Relative wall thickness and
      LV mass were significantly greater in the metabolic syndrome+ group, also after
      correction for body mass index. The LV systolic function was similar between the
      two groups, whereas all the parameters of diastolic function, but the mitral E/A
      ratio, were significantly lower in the metabolic syndrome+ group. From multiple
      regression analysis the main independent determinant of LV mass index was the
      presence of metabolic syndrome, followed by the 24-h systolic BP. CONCLUSIONS:
      Nondiabetic patients with metabolic syndrome showed more pronounced alterations
      of LV geometry and function compared with subjects without metabolic syndrome.
      These greater preclinical myocardial abnormalities were not accounted for by
      difference in age, gender, or 24-h BP and can be reasonably ascribed to the
      interplay of the metabolic syndrome components, making the metabolic syndrome in
      itself a relevant clinical problem, possibly a cardiovascular disease equivalent,
      that deserves aggressive treatment.

PMID- 16448894
TI  - Metabolic syndrome and left ventricular structure and functional abnormalities.

PMID- 16448895
TI  - Effect of losartan versus candesartan on uric acid, renal function, and
      fibrinogen in patients with hypertension and hyperuricemia associated with
      diuretics.
AB  - BACKGROUND: Hyperuricemia may counter benefits of blood pressure (BP) reduction,
      although this is controversial. METHODS: We examined the effects of candesartan
      and losartan on uric acid, creatinine, and fibrinogen. Patients with hypertension
      and serum uric acid > or = 0.42 mmol/L (7 mg/dL) associated with diuretics were
      randomized to receive losartan 50 to 100 mg or candesartan 8 to 16 mg for 24
      weeks. At randomization and after 24 weeks, systolic and diastolic BP, serum uric
      acid, creatinine, and fibrinogen were measured. RESULTS: A total of 59 patients
      were entered into the study (30 in the losartan and 29 in the candesartan group).
      Mean systolic and diastolic BP were reduced in the candesartan group, from 156 mm
      Hg at baseline to 132 mm Hg at 24 weeks, and from 90.9 to 80.8 mm Hg
      respectively, P < .0001), and in the losartan group from 150.3 to 132 mm Hg and
      from 89.6 to 77.6 respectively, P < 0001). Overall mean values of fibrinogen
      levels were again reduced from 4.39 g/L at baseline to 4.01 g/L at 24 weeks (P <
      .02). Mean values of serum uric acid in the losartan and candesartan groups were
      similar at baseline (0.44 and 0.46 mmol/L, respectively), but they were lower in
      the losartan group after 24 weeks (0.39 and 0.48 mmol/L, P = .01). Twelve
      patients (44%) in the candesartan group had a 10% increase in serum creatinine
      compared with four patients (14.2%) in the losartan group (P < .02). CONCLUSIONS:
      Candesartan and losartan lowered BP, but only losartan reduced uric acid. The
      lowering of fibrinogen in both groups may explain the reduction in stroke with
      angiotensin receptor blockers. The effect of persistent hyperuricemia on renal
      function requires further study.

PMID- 16448896
TI  - Atenolol and eprosartan: differential effects on central blood pressure and
      aortic pulse wave velocity.
AB  - BACKGROUND: Recent data suggest that atenolol may be inferior to other
      antihypertensive drugs in reducing cardiovascular risk in older individuals with
      hypertension, despite lowering peripheral blood pressure (BP). We hypothesized
      that that atenolol fails to reduce central BP as much as other agents. The aim of
      the present study was to compare the hemodynamic effects of atenolol and
      eprosartan in a double-blind, randomized, cross-over study. METHODS: After a 2
      week placebo run-in, 21 subjects with never-treated hypertension underwent 6
      weeks of therapy with atenolol (50 mg) and eprosartan (600 mg). Central BP and
      augmentation index were assessed using pulse wave analysis, and aortic pulse wave
      velocity was measured, at baseline and at the end of each treatment. RESULTS:
      Both drugs reduced peripheral BP to the same degree. However, there was a
      significantly greater reduction in central systolic BP with eprosartan (means +/-
      SEM: 16 +/- 3 v 11 +/- 2 mm Hg; P = .03). Despite identical reductions in mean
      pressure, atenolol reduced aortic pulse wave velocity more than eprosartan (0.8
      +/- 0.1 v 0.5 +/- 0.1 m/sec; P = .005). Conversely, augmentation index and N
      terminal pro-brain natiuretic peptide levels were reduced significantly after
      eprosartan (6% +/- 2% and 11 +/- 5 pg/mL, respectively) but were increased after
      atenolol (7% +/- 2% and 67 +/- 24 pg/mL, respectively). CONCLUSIONS: These data
      indicate that despite similar effects on peripheral BP and a greater effect on
      aortic stiffness, atenolol had less impact on central systolic BP than eprosartan
      because it failed to reduce wave reflection. This provides one potential
      explanation for the failure of atenolol to improve outcome in older patients with
      essential hypertension.

PMID- 16448897
TI  - Albumin-to-creatinine ratio predicts change in ambulatory blood pressure in
      normotensive persons: a 7.5-year prospective study.
AB  - BACKGROUND: The relationship between urinary albumin excretion and blood pressure
      (BP) has been found to be positive in hypertensive and normotensive subjects. It
      is not known, in a normotensive and nondiabetic sample, whether elevated urinary
      albumin levels predict future increases in BP. METHODS: In this prospective
      study, we followed a cohort of 108 individuals who were initially free of
      hypertension and diabetes for an average of 7.7 years. Urinary albumin excretion
      was determined at baseline by radioimmunoassay in a 24-h collection. Ambulatory
      BP monitoring was used to assess BP at baseline and at 7.5-year follow-up.
      Regression models were used to evaluate the relationship of baseline urinary
      albumin-to-creatinine ratio to baseline BP and average rate of change in BP
      before and after controlling for several potential confounding variables.
      RESULTS: Baseline albumin-to-creatinine ratio was not associated with baseline
      ambulatory BP, but was positively associated with change in ambulatory BP. Before
      and after controlling for sex, race/ethnicity, age, body mass index at baseline,
      and change in body mass index, urinary albumin-to-creatinine ratio was found to
      be a significant independent predictor of change in awake and sleep systolic and
      diastolic BPs (all P < .05). It also independently predicted hypertension status
      at follow-up. CONCLUSIONS: In healthy normotensive individuals, the urinary
      albumin-to-creatinine ratio predicts change in ambulatory BPs 7.5 years later.
      This finding suggests that urinary albumin excretion may be an important marker
      for processes that increase BP over time.

PMID- 16448898
TI  - Cross-sectional correlates of serum heat shock protein 70 in the community.
AB  - BACKGROUND: Recent studies of referral samples suggest that heat shock proteins
      play a key role in the pathogenesis of high BP and cardiovascular diseases (CVD)
      including heart failure. It is unclear whether circulating heat shock protein 70
      (HSP70) levels are related to CVD risk factors, echocardiographic indexes of left
      ventricular (LV) remodeling, and prevalent CVD in the population. METHODS: We
      evaluated the cross-sectional relations of serum HSP70 to established CVD risk
      factors (including hypertension), markers of oxidative stress (urinary 8-epi
      PGF(2alpha)) and inflammation (plasma interleukin-6, C-reactive protein, monocyte
      chemoattractant protein-1 MCP-1, and soluble intercellular adhesion molecule
      sICAM-1), echocardiographic LV dimensions and prevalent CVD in 456 Framingham
      Offspring Study participants (mean age 61 years, 42% women). RESULTS: In
      multivariable analyses, serum HSP70 was not associated with age, sex, vascular
      risk factors (including hypertension), echocardiographic LV mass or prevalent
      CVD. Also, serum HSP70 was not related to any of the biomarkers evaluated (p> or
      = 0.10 for all). CONCLUSIONS: In our community-based sample, serum HSP70 was
      similar in men and women, and not significantly related to traditional or novel
      risk factors, to LV mass or to prevalent CVD. Our data suggest that blood levels
      may not adequately reflect the important role of heat shock proteins in prevalent
      CVD.

PMID- 16448901
TI  - Genetics and molecular biology of intramedullary spinal cord tumors.

PMID- 16448902
TI  - Pathologic and epidemiologic findings of intramedullary spinal cord tumors.

PMID- 16448904
TI  - Clinical management of intramedullary spinal ependymomas in adults.

PMID- 16448903
TI  - Radiographic features of intramedullary spinal cord tumors.

PMID- 16448905
TI  - Spinal cord astrocytomas: presentation, management, and outcome.

PMID- 16448906
TI  - Spinal cord hemangioblastomas.

PMID- 16448907
TI  - Intramedullary spinal cord metastasis: clinical management and surgical
      considerations.

PMID- 16448908
TI  - Pediatric intramedullary spinal cord tumors.

PMID- 16448909
TI  - Orthognathic surgery for a patient with trichorhinophalangeal syndrome type I: a
      case report.
AB  - Trichorhinophalangeal syndrome (TRPS) type I is characterized by slowly
      progressing systemic osseous dysplasia, exhibiting craniofacial and other
      skeletal deformities. However, there have been few reports describing this
      syndrome after undergoing orthognathic surgery. In this report, we present a
      patient with TRPS I who successfully underwent orthognathic surgery. In addition,
      we examined the skeletal stability of the patient for 2 years after the surgery.

PMID- 16448910
TI  - Rhinolithiasis: an uncommon entity of the nasal cavity.
AB  - Rhinoliths are uncommon foreign bodies of the nose formed by in situ
      calcification of intranasal endogenous or exogenous foreign material. They are
      often an asymptomatic condition diagnosed accidentally during a routine
      examination. Although nasal foreign bodies are more frequently seen in children,
      and appear to be more common in women, they have been reported in patients of all
      ages. This article describes a case of rhinolith involving a 38-year-old male.
      The etiology, thin-sectioned microscopic findings, differential diagnoses, and
      treatment are also discussed.

PMID- 16448911
TI  - Oral histoplasmosis in an HIV-negative patient.
AB  - Histoplasmosis is a deep mycosis caused by Histoplasma capsulatum, which has been
      found in soil with accumulated excreta of bats and birds. This disease has
      variable clinical findings with only pulmonary or systemic involvement. Upper
      aerodigestive lesions are found mainly associated with systemic disease,
      affecting particularly patients with immunosuppression conditions mainly caused
      by HIV. However, it is uncommon in immunocompetent patients. This report
      describes a case of oro-laryngeal-esophageal histoplasmosis in a HIV-seronegative
      patient without detectable systemic involvement.

PMID- 16448912
TI  - Gonorrhea: update.
AB  - Gonorrhea is a worldwide sexually transmitted disease (STD) caused by Neisseria
      gonorrhoeae. Gonorrhea is the second most often reported STD in the United States
      behind chlamydia. An estimated 600,000 people each year in the United States are
      infected. Only about half this number of cases are reported. From 1975 through
      1997, the national gonorrhea rate declined 74.3%. After a small increase in 1998,
      the gonorrhea rate has decreased each year since 1999. In 2003 the South had the
      highest gonorrhea rate among the four regions of the country. Antimicrobial
      resistance remains an important consideration in the treatment of gonorrhea. In
      2003 the Gonococcal Isolate Surveillance Project found about 16% of collected
      isolates were resistant to penicillin and/or tetracycline. Since 1998 the number
      of ciprofloxacin-resistant isolates has been increasing with 270 (4.1%) being
      reported in 2003. Oral gonorrhea is rare, nonspecific, and varied and may range
      from slight erythema to severe ulceration with a pseudomembranous coating. The
      patient with gonorrhea poses little threat of disease transmission to the
      dentist. However, patients who have or have had gonorrhea should be approached
      with a measure of caution because they are in a high-risk group for additional
      STDs. The CDC has published recommendations for standard precautions to be
      followed in controlling infection in dentistry that have become the standard for
      preventing cross-infection. Strict adherence to these recommendations will, for
      all practical purposes, eliminate the danger of disease transmission between
      dentist and patient. Dentists should be aware of local statutory requirements
      regarding reporting STDs to state health officials. Syphilis, gonorrhea, and AIDS
      are reportable diseases in every state. Local health departments or state STD
      programs are sources of information regarding this matter.

PMID- 16448913
TI  - Hyperbaric oxygen results in an increase in rabbit calvarial critical sized
      defects.
AB  - OBJECTIVE: This study was undertaken to evaluate whether the effects of
      hyperbaric oxygen (HBO) therapy could alter the critical size for spontaneous
      healing of a bone defect in the rabbit calvarial model. STUDY DESIGN: An animal
      trial of 12 weeks duration was conducted using 20 New Zealand white rabbits,
      which were randomly divided into 2 groups of 10 animals each. Calvarial defects
      were created in the parietal bones of each animal bilaterally. Defects were
      critical-sized, 15 mm on one side and supra-critical-sized, 18 mm on the
      contralateral side. Group 1 received a 90-min HBO treatment sessions at 2.4
      absolute atmospheric pressure (ATA) per day for 20 consecutive days. Group 2
      served as a control without any HBO treatment sessions. Five animals in each
      group were sacrificed at 6 and 12 weeks. Data analysis included qualitative
      assessment of the calvarial specimens, post-sacrifice radiographs, as well as
      histomorphometric analysis to compute the amount of regenerated bone within the
      defects. ANOVA and paired sample t test were used for statistical analysis.
      RESULTS: Both radiographic analysis and histomorphometric analysis demonstrated
      that HBO-treated animals had significantly more new bone within their defects
      compared with the control group (P < .001). There was no statistically
      significant difference between the percentage of new bone forming in the 15-mm
      and 18-mm HBO-treated defects. There was no difference between the 6-week and the
      12-week HBO-treated groups. HBO is effective in enhancing the bony healing of
      full thickness critical sized as well as supra-critical-sized defects in the
      rabbit calvarial model. CONCLUSION: Bone regeneration was significantly greater
      in the HBO-treated animals regardless of the defect size. HBO may have increased
      the diameter of the rabbit critical-sized calvarial defect to more than 18 mm.

PMID- 16448914
TI  - The use of autologous fibrin glue for closing sinus membrane perforations during
      sinus lifts.
AB  - Sinus lift procedures depend greatly on fragile structures and anatomical
      variations. These procedures may cause sinus membrane perforations, which can
      lead to graft infection and early failure. The aim of this study was to assess
      the efficacy of autologous fibrin glue in the management of large perforations of
      the maxillary sinus membrane occurring during sinus lifts. After elevating the
      sinus membrane in the bilateral maxillary sinuses of 6 adult female mongrel dogs,
      a laceration (about 2.0 cm in length) was made in the membrane and either
      repaired with autologous fibrin glue or covered with a bioabsorbable collagen
      membrane as a control. Wounded areas were biopsied 2 weeks after the operation.
      Wounds repaired with autologous fibrin glue showed newly formed continuous
      epithelium across the previous perforation site. However, extensive fibrosis,
      inflammatory infiltration, and absent epithelium were observed in wounds treated
      with the collagen membrane control. Our results support the clinical use of
      autologous fibrin glue for repairing sinus membrane perforations.

PMID- 16448915
TI  - Is there any difference in the condylar position and angulation after asymmetric
      mandibular setback?
AB  - OBJECTIVE: This study was performed to compare the condylar position and
      angulation on 3-dimensional (3D) views between greater setback side (GSS) and
      lesser setback side (LSS) after asymmetric mandibular setback (AMS) using
      computed tomography. STUDY DESIGN: The sample consisted of 12 Korean skeletal
      class III malocclusion patients with mandibular prognathism and facial asymmetry,
      who underwent sagittal split ramus osteotomy (SSRO) with rigid fixation.
      Tomographs were taken 1 month before (T1) and 6 months after surgery (T2).
      Position and angulation of the condyles were measured. RESULTS: At T1 stage, the
      condylar head in GSS showed more forward inclination on the sagittal view (P <
      .05) than that of LSS. Although there were significant inward and backward
      rotations of the condylar head in GSS (P < .01) and significant backward rotation
      in LSS at T2 stage (P < .05), 3D positions of the condyle in GSS and LSS were not
      changed after AMS. CONCLUSION: SSRO might be effective to stabilize the condylar
      position for AMS.

PMID- 16448916
TI  - A comparative qualitative histological analysis of tissue-engineered bone using
      bone marrow mesenchymal stem cells, alveolar bone cells, and periosteal cells.
AB  - For tissue-engineered bone formation, autogenous osteogenic cells are of
      paramount importance for successful bone formation. In order to investigate the
      donor cell-related differences in tissue-engineered bone, cultured bone marrow
      mesenchymal stem cells, cultured alveolar bone cells, and cultured periosteal
      cells were examined for their in vivo potential to form bone. These cells were
      isolated from dogs, expanded in vitro, mixed with autologous fibrin glue and BMP
      2, and then injected into the subcutaneous space on the dorsum of nude mice. Bone
      formation was evaluated at 12 weeks. Histomorphometric analysis demonstrated that
      the subcutaneous nodules formed in nude mice contained 26.9% newly formed bone
      when using the bone marrow mesenchymal stem cells, 41.1% newly formed bone when
      using the alveolar bone cells, and 58.2% newly formed bone when using the
      periosteal cells. The results suggest that periosteal cells are the best choice
      for enhancing bone formation in tissue engineering of bone regeneration.

PMID- 16448917
TI  - One-year clinical course following visually guided irrigation for chronic closed
      lock of the temporomandibular joint.
AB  - OBJECTIVE: This study aimed to explore the clinical course following visually
      guided irrigation (VGIR) for chronic closed lock (CCL) of the temporomandibular
      joint (TMJ) as well as the factors of importance for clinical outcome. Evaluation
      emphasis was placed on the period needed for the patients to reach the success
      criteria. STUDY DESIGN: Sixty-one patients with unilateral CCL comprised the
      study group. The cumulative success rate of VGIR and the additional surgical
      treatments following VGIR were studied. The 61 patients were divided into either
      the good outcome (g) group or poor outcome (p) group on the basis of whether they
      reached the success criteria within 3 months postoperatively, and clinical and
      arthroscopic factors were correlated with the clinical outcome of VGIR. RESULTS:
      The cumulative success rate of VGIR increased up to the 6-month follow-up
      (success rate of 72.1%) but did not change after that point in time. A repeated
      VGIR (success rate of 87.5%) was performed in 8 patients. Open TMJ surgery
      (success rate of 87.5%) was performed in 8 patients, 7 of whom had an interfering
      condylar osteophyte. A pronounced reduction of preoperative painless range of
      mandibular motion (P-ROM) and advanced osteoarthritis (OA) were more frequently
      found in the p-group than in the g-group. The multivariate adjusted odds ratio
      showed that a decreased preoperative P-ROM was significantly predictive for a
      poor outcome of VGIR. CONCLUSIONS: The efficacy of VGIR is clinically acceptable
      as an initial surgical treatment for TMJ CCL. A 6-month follow-up period ought to
      be sufficient for outcome assessment of VGIR. A pronounced reduction of
      preoperative P-ROM should be considered as a risk factor for delay of the
      postoperative improvement, and OA changes may sometimes affect the clinical
      outcome of VGIR.

PMID- 16448918
TI  - Chronic graft versus host disease of oral mucosa: review of available therapies.
AB  - The use of hematopoetic stem cell transplantation (HSCT) has greatly expanded in
      the recent years for many neoplastic and hematological disorders. Chronic graft
      versus host disease (cGVHD) is a major complication of allogeneic HSCT and a
      major cause of morbidity and mortality. Oral mucosal involvement is frequent in
      cGVHD and contributes significantly to the overall burden of the condition. Oral
      medicine professionals should be familiar with various treatment options for oral
      cGVHD. This review discusses treatment modalities available for the management of
      oral mucosal manifestations of cGVHD. Available evidence for efficacy and safety
      of various systemic and topical agents, including corticosteroids, calcineurin
      antagonists, mycophenolate mofetil, and extracorporeal photopheresis, is
      reviewed.

PMID- 16448919
TI  - Oral lesions as an initial manifestation of dermatomyositis with occult
      malignancy.
AB  - Dermatomyositis (DM) is an inflammatory disease of skeletal muscle with
      characteristic cutaneous features. Oral manifestations of DM have been very
      rarely described. This case describes a patient in whom the oral lesions were
      among the initial manifestations of DM. The lesions were very painful and the
      most distressing component of the disease in this patient. High dose systemic
      steroids were required to control the lesions. Investigations for an occult
      malignancy in this patient resulted in the identification of a non-Hodgkin's
      lymphoma in her right kidney. Commencement of chemotherapy rapidly resulted in
      complete resolution of her oral and skin lesions.

PMID- 16448920
TI  - Sleep bruxism: clinical aspects and characteristics in patients with and without
      chronic orofacial pain.
AB  - OBJECTIVE: Evaluation of long-standing sleep bruxism (SB) patients. STUDY DESIGN:
      Descriptive study. RESULTS: One hundred subjects with SB (80 women and 20 men,
      mean age: 36.1+/-11.3 years) were evaluated according to the RDC/TMD and a pain
      questionnaire (EDOF-HC). The patients were divided into 2 groups: Group A-without
      (30.0%) and Group B-with orofacial pain (70.0%). AM stiffness: 36.4% in Group A
      and 88.6% in Group B; mean pain duration: 6.92 years; mean intensity of pain:
      4.33 (VAS); quality of pain: tightness/pressure (84.3%); 95.7% of Group B had
      myofascial pain. Depression and somatization levels were different between the
      groups (p = 0.001). Higher frequency of depression was found with body pain or
      presence of comorbidities. CONCLUSION: The data presented in this study showed
      statistical differences between long-standing bruxism without and with chronic
      facial pain; the two questionnaires allowed interaction between the chief
      complaint and the clinical findings; depression levels increased with pain in
      several regions of the body.

PMID- 16448921
TI  - Primary intraosseous odontogenic carcinoma arising in an odontogenic cyst or de
      novo: a clinicopathologic study of six new cases.
AB  - The term primary intraosseous odontogenic carcinoma (PIOC) has been primarily
      used to describe a squamous cell carcinoma within the jaws arising either from a
      previous odontogenic cyst or de novo. Here, we report 6 new cases of PIOC,
      affecting 4 female and 2 male patients with a mean age of 56.2 years. Two cases
      involved the maxilla and 4 cases occurred in the mandible. The typical
      radiographic presentation was that of a radiolucent lesion with well or ill
      defined margins. Histopathologically, 4 cases were diagnosed as well
      differentiated keratinizing PIOC arising from previous odontogenic cysts (2
      odontogenic keratocysts and 2 periapical cysts). The remaining 2 cases were
      poorly differentiated nonkeratinizing PIOC, which appeared to arise de novo.
      Treatment consisted of surgical removal, with postoperative radiotherapy in 5
      cases, and to date neither recurrence nor metastasis have occurred. Knowledge of
      the clinical, radiographic, and histopathologic features of PIOC allows accurate
      diagnosis and appropriate treatment of this rare malignancy.

PMID- 16448922
TI  - Cystadenocarcinoma of salivary gland presenting as a cystic lesion in the
      mandible.
AB  - Cystadenocarcinoma is a rare salivary neoplasm. It occurs in major and minor
      salivary glands and usually has a good prognosis. Mandibular involvement by
      salivary gland tumors at presentation is exceptionally rare. We present the first
      case, to our knowledge, of salivary gland cystadenocarcinoma appearing as a
      cystic lesion in the mandible.

PMID- 16448923
TI  - Cytokeratin expression in initial oral mucositis of head and neck irradiated
      patients.
AB  - OBJECTIVE: The aim of this work was to study cytokeratin (Ck) expression in
      initial radiation-induced oral mucositis. STUDY DESIGN: Eleven cases of initial
      radiomucositis of the buccal mucosa and 9 normal specimens were immunostained for
      Ck 1, 5, 6, 7, 8, 10, 14, 16, 18, and 19 by immunoperoxidase method. RESULTS:
      Expression of Ck 1, 6, 10, and 16 was stronger in mucositis than in normal
      mucosa. Ck 7, 8, and 18 were negative for both control and study groups. Ck 5,
      13, and 14 were positive for both groups, nevertheless suprabasal staining for Ck
      14 was more evident in mucositis than in the control group. Sporadic staining for
      Ck 19 was observed in 1 case of mucositis and in 2 controls. CONCLUSIONS:
      Increased Ck expression can be associated with the reactive proliferation of the
      epithelium and increasing resistance of the oral mucosa during the initial phases
      of radiotherapy.

PMID- 16448924
TI  - Dental findings in a family with hyperparathyroidism-jaw tumor syndrome and a
      novel HRPT2 gene mutation.
AB  - Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an important diagnosis because
      of the possible involvement of other family members and risk of malignant
      disease. We report clinical and genetic studies in a previously undocumented
      Australian family with HPT-JT. The proband and his sister presented with
      bilateral or recurrent mandibular radiolucencies diagnosed histopathologically as
      cemento-ossifying fibromas. Mutation screening of the recently identified disease
      gene HRPT2 was performed by direct sequencing in 3 affected members. This
      revealed a novel mutation in exon 1 of HRPT2 (nt 20AGGACG --> GGGAG), which is
      predicted to inactivate the parafibromin protein through protein truncation and
      premature termination of translation. The terminology used for the jaw lesions in
      this syndrome warrants review to become more consistent. Cemento-ossifying
      fibroma is the preferred term to better reflect the pathologies found in most
      individuals and families,and to emphasize the significance of the jaw lesions in
      the diagnosis of the syndrome.

PMID- 16448925
TI  - Effects of scintillator on the detective quantum efficiency (DQE) of a digital
      imaging system.
AB  - OBJECTIVE: To compare the effects of scintillator on the detective quantum
      efficiency (DQE) of a charge-coupled device (CCD) digital intraoral radiographic
      system. STUDY DESIGN: Three screens composed of 3 different scintillator
      materials, namely europium-doped lutetium oxide (Lu2(O3):Eu3+), transparent
      optical ceramic (TOC), thallium-doped cesium iodide (CsI:Tl; CsI), and terbium
      doped gadolinium oxysulfide (Gd2(O2)S:Tb; GOS) were compared, in turn, in
      combination with a CCD detector having square pixels with height and width
      dimensions of 19.5 microm. DQE was investigated using the slanted-slit-derived
      MTF and surrogate signal-to-noise ratio (SNR) measurements derived from
      calculations of the mean and standard deviations from the mean pixel values of
      multiple random patches from various uniform exposures. An Irix x-ray generator
      operated at 70 kVp and 8 mA, with a nominal focal spot size of 0.7 mm and 2.5 mm
      Al equivalent filtration, was used in making all exposures. RESULTS: Using TOC,
      the peak DQE was 62% at 5 cycles/mm. For CsI, the peak DQE was 22% at 2
      cycles/mm. With GOS, the peak DQE was 10% at 1 cycle/mm. CONCLUSION: Under
      identical experimental settings, TOC consistently resulted in higher DQE than CsI
      and commercially available GOS scintillators combined with the same high
      resolution solid-state detector.

PMID- 16448926
TI  - The role of SPECT/CT with 99mTc-MDP image fusion to diagnose temporomandibular
      dysfunction.
AB  - OBJECTIVE: The objective of this study was the evaluation of Single Photon
      Emission Computed Tomography with Technetium 99m Methylene Diphosphonate (SPECT
      with 99mTc-MDP) and computed tomography (CT), simultaneously acquired image in
      diagnosis of temporomandibular joint (TMJ) dysfunction. STUDY DESIGN: A
      prospective study was conducted with 33 patients, 29 female and 4 male, all of
      then presenting signs and/or complaints suggestive of temporomandibular
      dysfunction. SPECT/CT with 99mTc-MDP was performed in all patients and imaging
      results compared with final diagnosis and clinical outcome. RESULTS: The
      correlation of signs and symptoms with SPECT/CT imaging showed sensitivity 100%,
      specificity 90.91%, and accuracy 96.97%. CONCLUSIONS: SPECT/CT with 99mTc-MDP
      coregistered imaging fusion is a suitable method of temporomandibular dysfunction
      diagnosis, due to the sensitivity, specificity, and accuracy observed.

PMID- 16448927
TI  - Utility of diffusion-weighted images using fast asymmetric spin-echo sequences
      for detection of abscess formation in the head and neck region.
AB  - OBJECTIVE: The objective of this study was to evaluate the utility of new
      diffusion-weighted magnetic resonance images (DWI) using fast asymmetric spin
      echo (FASE) sequences for the detection of abscess formation in patients with
      phlegmon in the oral and maxillofacial regions. METHODS: We compared diffusion
      weighted images using FASE sequences with those using the gradient-echo type of
      echo-planar images (EPI) in 10 control volunteers and 10 patients with phlegmon
      in the oral and maxillofacial regions. RESULTS: Many kinds of tissues in the oral
      and maxillofacial regions were relatively well visualized in all subjects on FASE
      DWI, but not well on EPI-DWI. Apparent diffusion coefficients calculated from
      FASE sequences in abscess areas of patients with phlegmon were significantly
      lower than those in abscess-free areas; however, apparent diffusion coefficients
      calculated from EPI were not significantly different due to prominent distortion
      in small sample size study. CONCLUSIONS: We could accurately recognize the
      presence of abscess formation within inflammatory tissue in 5 patients with
      phlegmon using FASE-DWI. As an additional magnetic resonance examination, FASE
      DWI might be useful in the detection of abscess formation in the oral and
      maxillofacial regions.

PMID- 16448928
TI  - Epithelium and bacteria in periapical lesions.
AB  - OBJECTIVE: The purpose of this study was to evaluate 50 human periapical lesions
      for bacteria and epithelium in a case study in dental practice. STUDY DESIGN:
      Specimens were obtained from the extraction of 50 untreated teeth that had
      lesions attached to their apices. The specimens were histologically evaluated
      using serial sections. RESULTS: Bacteria were found in all teeth, colonizing
      necrotic tissue in the main canal, dentinal tubules, or apical ramifications, and
      in the body of the periapical lesion in 18 abscesses or cysts. Twenty-one lesions
      were epithelialized; 14 abscesses, 20 granulomas, and 16 cysts were
      distinguished. In 18 root canals inflamed tissue was found in the apical part of
      the canal. A single foramen was present in 13 cases while apical ramifications
      were found in 37 cases. CONCLUSIONS: Granulomas were most common, and most
      epithelialized lesions were cysts. Bacteria were only detected periapically in
      abscesses or cysts. Inflamed tissue was present in the apical root canal in one
      third of cases.

PMID- 16448929
TI  - Quantitative evaluation of the amount of apically extruded debris using 3
      different rotary instrumentation systems.
AB  - OBJECTIVE: To comparatively evaluate the amount of apically extruded debris when
      ProTaper, ProFile, and HERO Shaper were used for the instrumentation of root
      canals. STUDY DESIGN: Sixty human mandibular central incisor teeth were randomly
      assigned to 3 groups, 20 teeth in each. The teeth in the 3 groups were
      instrumented according to the manufacturers' instructions until the working
      length, with ProTaper, ProFile, and HERO Shaper rotary instruments respectively.
      The debris produced was collected in polyethylene tubes. The liquid inside the
      tubes was removed by lyophilization and the remaining debris was calculated for
      each group and compared. RESULTS: All instruments tested produced a measurable
      amount of debris. No statistically significant difference was observed between
      ProTaper and HERO Shaper in terms of debris extrusion (P > .05). Similarly, no
      statistically significant difference was observed between ProFile and HERO Shaper
      even though HERO Shaper extruded a relatively higher amount of debris (P > .05).
      On the other hand, ProTaper extruded significantly more amount of debris compared
      to ProFile (P < .001). CONCLUSIONS: ProTaper caused a significantly higher amount
      of debris extrusion compared to ProFile. No statistically significant difference
      was observed among the other groups tested. As the quantity of debris extrusion
      is not the only factor responsible for acute exacerbations, future studies can be
      planned that focus on the types of bacteria causing flare-ups and methods for
      their elimination.

PMID- 16448931
TI  - Cardiopulmonary exercise testing in obstructive sleep apnea syndrome.
AB  - To investigate whether cardiac dysfunction or abnormal measurements on
      cardiopulmonary exercise testing (CPET) are present in patients with obstructive
      sleep apnea syndrome (OSAS) and what factors are responsible for exercise
      limitation in these patients. We enrolled 20 patients with moderate or severe
      OSAS in the OSA group and 20 subjects without OSAS in the control group. All
      subjects underwent a sleep study and cardiac evaluation by radionuclide scanning
      and CPET. There was no difference in left ventricular ejection fraction (VEF)
      between the two groups, but the OSA group had a lower right VEF. Patients in the
      OSA group had a lower VO2(peak), VO2(peak/kg) and workpeak than the control
      group. The OSA group had a higher breathing reserve and a greater decrease in
      anaerobic threshold (AT) and oxygen pulse. In conclusion, patients with moderate
      to severe OSAS had abnormal CPET results. These abnormalities may be due to
      cardiac disease, pulmonary vascular disease, or possible lack of fitness.

PMID- 16448930
TI  - Genotoxicity and cytotoxicity of mineral trioxide aggregate and regular and white
      Portland cements on Chinese hamster ovary (CHO) cells in vitro.
AB  - OBJECTIVE: Recently, mineral trioxide aggregate (MTA) and Portland cement have
      been used in dentistry as root-end-filling materials. However, the reported
      results concerning the biocompatibility of these materials are inconsistent. The
      goal of this study was to examine the genotoxicity and cytotoxicity of MTA and
      Portland cements in vitro by the single-cell gel (comet) assay and trypan blue
      exclusion test. STUDY DESIGN: Chinese hamster ovary (CHO) cells were exposed to
      MTA and regular and white Portland cements at final concentration ranging from 1
      to 1000 microg/mL for 1 h at 37 degrees C. RESULTS: All compounds tested did not
      show genotoxic effects in all concentrations evaluated. No significant
      differences (P > .05) in cytotoxicity were observed for all compounds tested.
      CONCLUSIONS: Taken together, our results suggest that MTA and Portland cements
      are not genotoxins and are not able to induce cellular death.

PMID- 16448932
TI  - Reproducibility of measurements of inspiratory work capacity in cystic fibrosis
      patients.
AB  - The evaluation of respiratory muscle endurance (RME) is regarded as being
      clinically relevant to the assessment of respiratory muscle function. The
      reproducibility of a non-invasive measure of assessing RME was determined by
      measuring inspiratory work capacity (IWC) (using a computerised system).
      Measurements were obtained on two occasions in 20 adult cystic fibrosis (CF)
      patients (22.7+/-3.4 years, mean+/-S.D.) and 20 age (23.4+/-4.4 years) and gender
      (10 male, 10 female in each group) matched healthy controls. The coefficients of
      reliability (CR), intra-class correlation coefficients (ICC) and limits of
      agreement (bias+/-2 S.D.) were determined. CR values for the CF patients and
      controls were above 90% and with ICC of 0.99 in both CF patients and controls.
      The differences in IWC between study days were within +/-2 S.D. of the mean
      difference in all but one CF and one control subject. These data suggest that
      measures of IWC may be considered reliable when used to assess RM function in
      both controls and in patients with CF.

PMID- 16448933
TI  - Mechanical loads modulate tidal volume and lung washout during high-frequency
      percussive ventilation.
AB  - High-frequency percussive ventilation (HFPV) has been proved useful in patients
      with acute respiratory distress syndrome. However, its physiological mechanisms
      are still poorly understood. The aim of this work is to evaluate the effects of
      mechanical loading on the tidal volume and lung washout during HFPV. For this
      purpose a single-compartment mechanical lung simulator, which allows the
      combination of three elastic and four resistive loads (E and R, respectively),
      underwent HFPV with constant ventilator settings. With increasing E and
      decreasing R the tidal volume/cumulative oscillated gas volume ratio fell, while
      the duration of end-inspiratory plateau/inspiratory time increased. Indeed, an
      inverse linear relationship was found between these two ratios. Peak and mean
      pressure in the model decreased linearly with increasing pulsatile volume, the
      latter to a lesser extent. In conclusion, elastic or resistive loading modulates
      the mechanical characteristics of the HFPV device but in such a way that washout
      volume and time allowed for diffusive ventilation vary agonistically.

PMID- 16448934
TI  - Effect of high-fat diet and metformin treatment on ventilation and sleep apnea in
      non-obese rats.
AB  - We investigated the effect of insulin resistance on ventilation and the incidence
      of sleep apnea in non-obese rats and determined whether metformin could change
      ventilation and occurrence of sleep apneas. Five groups of rats were studied: (1)
      standard chow; (2) high-fat groups, with 1 with metformin; (2) had type 2
      diabetes induced by streptozotocin, with 1 with metformin. Compared to standard
      rats, ventilatory parameters remained unchanged in the high-fat fed diet as well
      as in diabetic rats. However, their oxygen consumption was reduced (p<or=0.01).
      They had a lower ventilatory response to CO2 challenge (p<or=0.01), and their
      sleep apnea scores increased markedly (p<or=0.001). These results suggest that
      insulin resistance could impair the ventilation control. Metformin treatment,
      known to reduce insulin resistance, got sleep apnea scores back to their basic
      levels, reinforcing the idea that insulin resistance is a major factor in the
      occurrence of apneas in this rat model.

PMID- 16448935
TI  - Optimized analysis of surface electromyograms of the scalenes during quiet
      breathing in humans.
AB  - Studying the inspiratory recruitment of the scalenes is clinically relevant, but
      the interpretation of surface electromyographic (EMG) recordings is difficult.
      The aim of this study was to optimize an averaging method to analyze the surface
      EMG activity of the scalenes. Ten healthy subjects were studied. Nasal flow and
      surface EMG of the right scalene were recorded during 15 min epochs of quiet
      breathing. In four subjects, needle scalene EMG was also recorded. The flow
      signal was used to trigger the ensemble averaging of the ventilatory wave forms
      from 80 consecutive breaths. In eight cases, this evidenced a phasic inspiratory
      activation of the scalenes and permitted the determination of the
      electromechanical inspiratory delay (134+/-55 ms) and post-inspiratory activity
      (811+/-233 ms). When simultaneously available, surface and intramuscular
      recordings provided identical results. An averaging method triggered from a
      respiratory flow signal can identify and characterize a low phasic inspiratory
      activity of the scalenes within a noisy surface signal.

PMID- 16448936
TI  - Typhlocolitis associated with spirochaetes in goose flocks.
AB  - The role of Brachyspira bacteria in the aetiology of increased mortality observed
      in two breeder goose flocks (Flock A consisting of 1,500 and Flock B comprising
      4,500 laying geese) at the end of the first egg-laying season, in the period of
      moulting, was studied. In Flock A 415 geese (28%) died during an 8-week period
      while in Flock B 834 geese (18%) died during a 12-week period. On gross
      pathological examination, the geese were found to have haemorrhagic-to-necrotic
      inflammation of the large intestine (colon and rectum) and fibrinonecrotic
      typhlitis accompanied by severe degeneration. Often, fibrosis of the kidneys, and
      in five of the geese secondary visceral urate deposition ("visceral gout") was
      also observed. Histopathological examination consistently demonstrated
      spirochaetes in the mucous membrane of the affected large intestine. This was
      confirmed by the results of immunohistochemical and electron microscopic
      examination. In addition, Trichomonas stages were also detected from the large
      intestine of 11 geese. On the basis of their cultural and biochemical properties,
      and PCR sequencing analysis, eight out of the nine spirochaete strains isolated
      from the geese by culture on special media under anaerobic conditions were
      identified as Brachyspira alvinipulli. This is the first report on the isolation
      of B. alvinipulli from laying geese affected with fibrinonecrotic typhlocolitis.

PMID- 16448937
TI  - Antimicrobial susceptibility testing of Brachyspira intermedia and Brachyspira
      pilosicoli isolates from Australian chickens.
AB  - Susceptibilities of predominantly Australian isolates of the pathogenic
      intestinal spirochaetes Brachyspira intermedia (n = 25) and Brachyspira
      pilosicoli (n = 17) from chickens were tested in agar dilution against four
      concentrations each of the antimicrobials tiamulin, lincomycin, tylosin,
      metronidazole, tetracycline and ampicillin. Based on available minimum inhibitory
      concentration (MIC) breakpoint values for Brachyspira hyodysenteriae or other
      Gram-negative enteric veterinary pathogens, isolates of both species generally
      were susceptible to tiamulin, lincomycin, metronidazole and tetracycline.
      Although not classed as resistant, four isolates of B. intermedia had an elevated
      MIC range for tiamulin (1 to 4 mg/l), 11 isolates of B. intermedia and five of B.
      pilosicoli had an elevated MIC range for lincomycin (10 to 50 mg/l), one isolate
      of B. pilosicoli had an elevated MIC range for tetracycline (10 to 20 mg/l), and
      one isolate of B. intermedia and five of B. pilosicoli had an elevated MIC range
      for ampicillin (10 to 50 mg/l). A clear lack of susceptibility to tylosin (MIC >
      4 mg/l) was seen in 11 isolates each of B. intermedia and B. pilosicoli, and to
      ampicillin (MIC > 32 mg/l) in two isolates of B. pilosicoli. These data suggest
      that some resistance to common antimicrobials exists among intestinal spirochetes
      obtained from laying hens and supports the need of MIC data for clinical isolates
      before any treatment is considered.

PMID- 16448938
TI  - Pathology and tissue distribution of West Nile virus in North American owls
      (family: Strigidae).
AB  - This study describes the macroscopic and microscopic lesions and the viral
      antigen distribution in 82 owls (Family: Strigidae) of 11 North American and one
      Eurasian species that died following natural West Nile virus infection. The range
      of lesions seen was greater than that previously reported for owls, and involved
      more organs. Two patterns of antigen distribution were identified: one that
      involved the blood and all major organs; and a second where antigen was sparse,
      localized, and absent from the blood. The first pattern was associated with
      species of northern natural breeding range, while the second was seen in owls of
      a more southern distribution and appeared to be associated with a more prolonged
      course of illness. Further differences in lesion and antigen distribution
      appeared to be either species related or individual. The findings underline the
      complexity and variability of West Nile virus pathology within birds of a
      relatively narrow taxonomic group.

PMID- 16448939
TI  - Observations on detection, excretion and transmission of pigeon circovirus in
      adult, young and embryonic pigeons.
AB  - Infections with pigeon circovirus (PiCV) occur in young racing pigeons and
      pigeons raised for meat production and have been reported worldwide, but
      relatively little is known about the disease induced by PiCV infection. The aim
      of this study was to investigate how PiCV is transmitted. Using a sensitive
      polymerase chain reaction (PCR) test, the presence of PiCV was investigated in a
      wide range of samples from adult pigeons, embryos, breeders and young birds,
      which were derived from a racing loft that had a clinical history of "young
      pigeon sickness" and in which PiCV had been previously been diagnosed. Using PCR,
      PiCV DNA was detected in tissues of 13/20 apparently healthy older birds, aged
      from 1 to 9 years. Viral DNA was most commonly detected in the respiratory
      organs, including the trachea, pharynx and lung, followed by tissues such as the
      spleen, kidney and liver. It was also detected in the ovary and/or testes of some
      birds. This finding, and the detection of viral DNA in tissues from 8/22 embryos,
      suggested that PiCV may be vertically transmitted. Testing of pharyngeal and
      cloacal swabs, and blood samples, collected immediately before the death of the
      adult pigeons, failed to detect all birds found to be infected at necropsy,
      suggesting that testing of potential breeding birds would not enable exclusion of
      infected birds from breeding programmes. Additional PCR testing of cloacal swab
      samples obtained sequentially from 19 young pigeons showed that while four were
      excreting virus when 15 days old, only one bird was excreting at the time of
      weaning (28 days old). The detection of viral DNA in cloacal swab samples from
      15.8% of the birds when 37 days old and 100% of birds when 51 days old suggested
      that most young pigeons probably became infected in the rearing loft.

PMID- 16448940
TI  - The effect of vaccination with a bacterin on the horizontal transmission of
      Mycoplasma gallisepticum.
AB  - The effect of an inactivated vaccine on the horizontal transmission of Mycoplasma
      gallisepticum was quantified in a transmission model. Twenty non-vaccinated and
      20 vaccinated 23-week-old specific pathogen free hens were housed in pairs, while
      five individually housed hens acted as a negative control group. Each pair
      consisted of a challenged chicken (10(4) colony forming units intratracheally)
      and a non-challenged susceptible contact bird. Infection was monitored by
      serology, quantitative polymerase chain reaction and culture. All non-vaccinated
      and vaccinated in-contact chickens became infected with M. gallisepticum. The 95%
      confidence interval of the reproduction ratio, R (a measure of transmission
      defined as the average number of secondary cases caused by one infectious
      individual) was 4.48 to infinity in both groups. However, the logarithm of the
      area under the curve in the vaccinated group was 0.51 lower (P = 0.02) than in
      the non-vaccinated group, indicating that there was an effect of vaccination on
      the levels of potential shedding of M. gallisepticum. Nevertheless, the results
      of this study indicate that the use of an inactivated M. gallisepticum vaccine
      will not reduce the horizontal transmission of M. gallisepticum between laying
      hens.

PMID- 16448941
TI  - Acute poisoning of silver gulls (Larus novaehollandiae) following urea fertilizer
      spillage.
AB  - Two episodes of accidental urea toxicosis are described in wild silver gulls
      (Larus novaehollandiae) following spillage of fertilizer grade urea at a
      commercial shipping facility near Perth, Western Australia. In both cases, urea
      spillage had been seen to contaminate freshwater wash-down pools on the wharves
      where ships were being unloaded and gulls were seen to be drinking and washing in
      the pools nearby the spillages. Affected birds were found moribund or dead.
      Necropsy and histopathological findings were non-specific and consisted of mild
      to moderate congestion of visceral organs and brain. Analysis of a water sample
      collected during Case 1 revealed a very high urea concentration of 4.124 mol/l
      (pH 5.5), and fluid from the proventriculus of two birds had urea concentrations
      of 382 and 308 mmol/l, respectively. Nine birds were examined during the second
      episode (Case 2) and, from heparinized heart blood samples collected (n = 5), the
      mean plasma urea (288 +/- 92.0 mmol/l), ammonia (43.9 +/- 34.2 mmol/l) and uric
      acid (7.45 +/- 1.99 mmol/l) concentrations were markedly elevated above the
      reference ranges for all bird species. Proventricular contents (n = 7) similarly
      contained high concentrations of urea (394 +/- 203 mmol/l) and ammonia (9.3 +/-
      15 mmol/l). The probable mechanisms of urea and ammonia toxicity in these birds
      are discussed.

PMID- 16448942
TI  - Relationship between Marek's disease virus load in peripheral blood lymphocytes
      at various stages of infection and clinical Marek's disease in broiler chickens.
AB  - Vaccination with herpesvirus of turkey (HVT) vaccine provides protection against
      clinical Marek's disease (MD) but does not preclude infection with wild-type MD
      virus (MDV). The quantity of MDV detected in circulating lymphocytes during the
      early period after infection may be a useful predictor of subsequent clinical MD
      later in the life. A study was designed to quantify MDV and HVT copy number in
      peripheral blood lymphocytes (PBL) using real-time polymerase chain reaction
      between days 5 and 35 post-challenge and to relate this to subsequent development
      of gross MD lesions. Female commercial broiler chickens were vaccinated with HVT
      or were sham-vaccinated at hatch, then challenged with MDV strain MPF-57 at day 2
      post-vaccination and reared in positive-pressure isolators up to 56 days post
      challenge, when all survivors were euthanized. All dead and euthanized chickens
      were examined post mortem for gross MD lesions. Birds were scored for MD lesions
      and mortality. MDV and HVT genome copy numbers were determined for each PBL
      sample. There was an increase in HVT load in PBL between days 7 and 37 post
      vaccination, with marked increases between days 7 and 16 and again between days
      30 and 37. There was a steady increase in MDV load to 35 days post-challenge. The
      mean MDV copy number (log(10)) was greater in chickens subsequently exhibiting
      gross MD lesions (5.05 +/- 0.21) than in those that did not (2.88 +/- 0.223),
      with the largest difference at 14 and 21 days post-challenge (P < 0.001).
      Quantification of MDV during early infection is therefore a potential tool for
      monitoring MD in broiler flocks.

PMID- 16448943
TI  - Pathology of goose haemorrhagic polyomavirus infection in goose embryos.
AB  - Goose embryos were infected with goose haemorrhagic polyomavirus (GHPV) onto the
      chorioallantoic membrane (CAM) in order to examine the effect of GHPV on the
      embryos and to obtain data on whether embryos could develop into infected, virus
      shedding goslings, as well as to present an accurate biological method for virus
      titration. The reported method of infection could offer a possibility to express
      the virus titre as the median embryo infective dose (EID(50)). As a special
      pathological feature of the disease, extensive cerebral haemorrhages were
      observed, which protruded the skullcap in many cases. Some embryos infected with
      10(1.25) or 10(0.25) EID(50)/0.2 ml were able to hatch; however, they were in
      poor physical condition and died by post-hatching day 4 showing haemorrhagic
      nephritis and enteritis of geese. Virus shedding was revealed by polymerase chain
      reaction. The ability of some of the infected goose embryos to hatch may indicate
      the potency of GHPV to spread vertically, although this needs further study for
      confirmation.

PMID- 16448944
TI  - Exocrine pancreatic insufficiency in pigeons.
AB  - Exocrine pancreatic insufficiency (EPI) is a well-studied syndrome in domestic
      animals. EPI occurs when severe progressive loss of tubulo-acinar tissue from
      atrophy or inflammatory destruction results in insufficient secretion of
      digestive enzymes and clinical signs of malabsorption. However, the literature on
      EPI in birds is limited. The syndrome has been previously described in several
      cases where the diagnosis was based on clinical signs due to malabsorption-like
      light-coloured voluminous faeces, voracious appetite, coprophagia and weight
      loss, and on the response to treatment with pancreatic enzyme formulas. To enable
      a more scientific approach to the diagnosis of pancreatic functional disorders in
      pigeons, reference values of plasma amylase (382 to 556 IU/l), lipase (0 to 5
      IU/l), and faecal activities of amylase (13 to 16 IU/l) and trypsin (11 to 14
      IU/l) were determined in 24 adult pigeons. A case of EPI in a racing pigeon
      (Columba livia domestica) is reported, based on the clinical signs and the
      measurement of faecal amylase and trypsin activity.

PMID- 16448945
TI  - Typing infectious bronchitis virus strains using reverse transcription-polymerase
      chain reaction and restriction fragment length polymorphism analysis to compare
      the 3' 7.5 kb of their genomes.
AB  - Typing infectious bronchitis virus (IBV) strains is useful for implementation of
      control measures and for understanding the epidemiology and evolution of IBV. The
      aim of the work reported here was to develop a rapid and sensitive method for
      typing isolates of IBV, if possible directly from tissues of infected birds. A
      procedure was developed for differentiation of IBV strains by restriction
      endonuclease fragment length polymorphism (RFLP) analysis of a 7.5 kb DNA
      fragment amplified from their genome by reverse transcription-polymerase chain
      reaction (RT-PCR). This fragment encompassed all of the genes encoding the
      structural proteins of the virus. Viral RNA was extracted either directly from
      tissues of diseased birds or from virus propagated in embryonated eggs, and was
      subjected to RT-PCR. Three different restriction endonucleases, AluI, Sau3AI and
      MnlI, were used to digest the 7.5 kb PCR product from different IBV strains and
      the resultant RFLP patterns were compared. Patterns obtained with all three
      enzymes grouped IBV strains belonging to the same serotype in the same cluster.
      These results show that the RT-PCR-RFLP system described here can be used as a
      quick and inexpensive tool for differentiating IBV strains.

PMID- 16448946
TI  - Diversity in sexual health: problems and dilemmas.
AB  - The increase in migrant populations in western Europe has led to specific
      problems and dilemmas in the area of sexual and reproductive health and service
      provision. In general, these problems and dilemmas can be divided into four
      categories: (1) epidemiology of diseases and risk factors; (2) psychosocial and
      cultural aspects; (3) communication; and (4) moral and ethical dilemmas.
      Regarding epidemiology, there is an increased prevalence in migrant groups of
      unwanted pregnancy and abortion, HIV/STDs, and sexual violence. Effective
      contraceptive use is hampered by knowledge deficits, uncertain living conditions,
      ambivalence regarding the use of contraceptives, and problems accessing
      (information on) contraception. Psychosocial and cultural aspects relate to the
      norms and attitudes individuals and groups have regarding the family, social
      relationships, sexuality, and gender. These norms and attitudes have an impact on
      the sexual and reproductive choices people make and the possibilities and
      restrictions they feel in this respect. Problems in communication concern not
      only language but also communication styles, the way patients present their
      problems, and the expectations they have from the service provider. Communication
      problems inevitably lead to a lower quality of care. Moral and ethical dilemmas
      arise where cultures collide, for example regarding sexuality education and
      virginity problems. Two examples of practical situations in which migrant
      patients ask for help with sexual or reproductive health problems will be
      described.

PMID- 16448947
TI  - Microbicidal spermicide or spermicidal microbicide?
AB  - Vaginal contraception, the oldest method of fertility regulation that remained
      virtually forgotten for a few decades has recently come under focal review due to
      an increase in STDs and HIV infections worldwide. Today it is being considered
      very strongly that a conceptual microbicidal spermicide can tender protection
      against pregnancy as well as STDs (including AIDS), simultaneously. However the
      two activities (spermicidal and microbicidal) need to be integrated in vaginal
      preparations, as many women across the world may be concerned more about the
      unwanted pregnancy rather than the STI during a coital act. A strong detergent
      like nonoxynol-9 (N-9) has been used as a spermicide in many local contraceptive
      preparations and studies have shown that it also exhibits significant
      microbicidal activity in vitro. However, recent clinical trials have shown that
      detergent spermicides do not provide any protection against STDs and AIDS but may
      in fact even promote their transmission. This anomaly has largely been attributed
      to their surfactant nature that irritates the vagina and kills the normal vaginal
      flora making it more susceptible to STD infections. An urgent need for a suitable
      non-detergent spermicide has thus emerged to replace N-9 in local contraceptive
      preparations. Anticipating the potential of spermicide-based vaginal
      contraceptives in the reproductive health of women, a large number of synthetic,
      non-detergent molecules were designed and evaluated at this Institute over recent
      years. Simultaneously, a number of natural products from terrestrial plants and
      marine flora/fauna were also evaluated for spermicidal activity. A local
      contraceptive preparation incorporating the active ingredient from the fruit
      pericarp of Sapindus mukorossi has successfully completed Phase III clinical
      trials in India and is ready for marketing. Recent studies have indicated that in
      comparison to N-9, this ingredient is much less toxic to Lactobacillus spp. and
      effectively inhibits the growth of Trichomonas vaginalis in vitro. Other
      candidate spermicides/microbicides under development worldwide have been reviewed
      briefly.

PMID- 16448948
TI  - Contraceptive use patterns among Spanish single youth.
AB  - OBJECTIVE: To examine sexual and contraceptive use patterns, including method
      choice, among unmarried youth in Spain. METHOD: The analysis is based on the 1999
      Youth Survey. The analytical sample comprised 696 never-married sexually
      experienced women aged 15-24 and 1070 men. Logistic regression was used to assess
      the influence of various socio-demographic factors on contraceptive use, and
      multinomial logistic regression was used to examine the determinants of method
      choice. RESULTS: Given the trend towards earlier sexual initiation and increasing
      marriage postponement, sexual activity prior to marriage has become the norm in
      Spain. Nine out of 10 sexually active single youth reported contraceptive use at
      their last intercourse. Differentials across social subgroups were small, with
      the exception of those based on educational level. Young women and men with more
      than one partner in the previous year and those not currently in a stable
      relationship were more likely to engage in unprotected intercourse. Regarding the
      choice of method, the analysis revealed that, although condom is the dominant
      method, there is a tendency to shift to the pill with increasing age and
      relationship stability. CONCLUSION: The level of contraceptive protection among
      unmarried youth is reasonably high, but a nontrivial proportion of youth engage
      in unprotected sexual activity.

PMID- 16448949
TI  - The unmet need for contraception among Nigerian women in the first year post
      partum.
AB  - OBJECTIVE: To determine the level of Unmet need for Contraception among women in
      the first year post-delivery in Ile-Ife, Nigeria. METHODS: A prospective study of
      256 women attending antenatal clinic of the OAUTHC, Ile-Ife, Nigeria was carried
      out 9-10 months post-delivery. Using a semi-structured questionnaire, the
      respondents were interviewed for socio-demographic characteristics; obstetric,
      sexual, and contraception history were also taken. The data were analyzed using
      descriptive and inferential statistical methods. RESULTS: There was a high level
      of unmet need (59.4%) in the sample of Nigerian women despite a high level of
      awareness of common methods of contraception. Education and parity had no
      significant effect on usage of contraception (p > 0.05). No reason was given for
      non-usage in the largest proportion (30.3%) of the non-users. Only one-third of
      the respondents could correctly report the 'at-risk' period for getting pregnant
      in the post-partum period. CONCLUSION: There is a need to study in more detail
      the social and cultural factors that determine contraceptive utilization before
      success can be achieved in closing the gap of unmet need, as it has become
      evident that increasing the awareness and knowledge of contraception is not
      enough to achieve the objectives of family-planning programs.

PMID- 16448950
TI  - What do clients of a young people's sexual health service recall about their sex
      education programme at school?
AB  - OBJECTIVES: To assess young people's recall of school-based sexual health
      education. METHODS: Clients attending The Place, an open-access sexual health
      service for young people, were asked to recall whether they had received teaching
      on key areas of sex education outlined in the Scottish Executive's draft Sexual
      Health and Relationship Strategy and Greater Glasgow NHS Board's guidelines for
      sex education in schools.Their responses were analyzed by age, sex, and type of
      school attended. RESULTS: Although most could remember receiving some teaching
      about risks of sexual activity, there was little recall of teaching in positive
      areas of sexual health, such as having good relationships, rights and
      responsibilities, and being good parents. CONCLUSIONS: Further research is needed
      to establish why recall of taught sex education is low in this group of clients,
      and how to improve retention of important sexual education information.

PMID- 16448951
TI  - Influence of discipline of study on contraceptive usage among undergraduates in
      Southwest Nigeria.
AB  - OBJECTIVE: To determine the influence of discipline of study on contraceptive
      usage among undergraduates in southwest Nigeria. METHODS: A comparative cross
      sectional study of students from medical and nonmedical disciplines was carried
      out. RESULTS: A total of 387 undergraduates were investigated, out of which 198
      (55.8%) were from medical disciplines (MD), and 189 (44.2%) were from nonmedical
      discipline (NMD). Out of the total number of respondents (387), 229 (59.2%), were
      sexually active, out of which 26.2% had been sexually active without
      contraception with a greater proportion of students of NMD being affected (p <
      0.05). Students from MD had a better knowledge (71.9%) of contraception than
      those from NMD (28.1%). However, more students from NMD use contraceptives (62%)
      compared to those from MD (54%) (p < 0.05). Despite this, more students from NMD
      became pregnant despite contraceptive use (11%) compared to those from MD (5.1%)
      (p < 0.05). The condom was the most commonly used contraceptive among both
      disciplines. The peer group was the commonest source of information on
      contraception. CONCLUSION: Discipline of study has an important influence on
      contraceptive usage. This is a pointer to the absolute need for adequate
      contraceptive education for every student, irrespective of the discipline of
      study.

PMID- 16448952
TI  - First-trimester pregnancy termination with 800 microg of vaginal misoprostol
      every 12 h.
AB  - The objective of the study was to evaluate the efficacy and safety of 800 microg
      of misoprostol every 12 h, for a period of 36 h for pharmacological abortion. A
      group of 162 volunteer women with gestations between 50 and 63 days received
      misoprostol every 12 h up to a maximum of three doses for abortion. Outcome
      measures assessed included: successful abortion (complete abortion without
      requiring surgery), side effects, and a decrease in hemoglobin, mean time of
      vaginal bleeding, mean expulsion time and mean time of returning of menses.
      Complete abortion occurred in 148 of 162 (91%, 95% confidence interval 87.95)
      patients. The mean decrease in hemoglobin was statistically significant (p =
      0.001). Vaginal bleeding lasted 8.0 +/- 3.2 days, spotting 8.0 +/- 3.5 days, and
      total bleeding 16 +/- 4.0 days. The mean expulsion time was 8.5 +/- 4.0 h.
      According to the observed outcomes, 800 microg of misoprostol vaginally could be
      a valid method to terminate pregnancies up to 9 weeks of gestation.

PMID- 16448953
TI  - Prevalence of sexual activity and family-planning use among undergraduates in
      Southwest Nigeria.
AB  - OBJECTIVE: To assess the prevalence of sexual activity and family-planning use
      among undergraduates in a private tertiary institution in Nigeria. METHODS: A
      cross-sectional survey of 283 undergraduate students. RESULTS: Out of 283
      students, 245 (86.6%) are sexually active in the last month. Out of these 245,
      219 (89%) are currently using a family-planning method. In the study population,
      the percentages of awareness, ever use, and current users are 89%, 77%, and 75%,
      respectively. The most commonly known, ever used, and currently used
      contraceptive is condom followed in descending order by calendar method, oral
      pills, coitus interruptus, injectable contraception, emergency contraception,
      intrauterine contraceptive device, and diaphragm. Unmarried students and male
      gender show statistical significance with condom use. The reasons for preferring
      the current contraceptive method, among 219 current users, include safety, cost,
      ready availability, and partner's preference, among others. Most of the nonusers
      gave no reason for a failure to use a contraceptive, but others felt that
      contraceptives are dangerous, while a minority were ignorant of any method.
      Though many use a condom, this use is inconsistent. CONCLUSION: There is a high
      level of sexual activity among these undergraduates. Many are aware of family
      planning, and the condom is the most commonly known and used method, though not
      consistently. Reproductive-health education should be promoted among youths in
      Nigeria.

PMID- 16448954
TI  - Colonoscopic retrieval of a lost intrauterine contraceptive device: a case report
      and review of articles.
AB  - A case of translocated intrauterine contraceptive device (IUCD) lying partly in
      the bowel wall at the rectosigmoid junction and its removal by colonoscope is
      described. This case highlights the possibility of safe retrieval of an IUCD by
      colonoscopy when it is partly embedded in the bowel wall. Routine sigmoidoscopy
      alongside other investigations is recommended for translocated IUCDs. Its use can
      select those patients for whom rectal recovery of the IUCD is feasible, thus
      avoiding unnecessary surgical intervention.

PMID- 16448955
TI  - The evaluation of 318 intrauterine pregnancy cases with an intrauterine device.
AB  - OBJECTIVE: To determine the factors affecting the pregnancies with intrauterine
      devices. DESIGN AND METHODS: The intrauterine device (IUD) locations in
      pregnancies with IUDs referring to SSK Aegean Maternity Hospital were determined
      by ultrasonography (USG) in a 6 year period. Three hundred and eighteen pregnancy
      cases (pregnancy group) were observed together with intrauterine devices. All
      intervally applied IUDs were CeT380A. All demographic characteristics of the
      cases together with determination of IUD localizations were recorded, and these
      cases were compared with 300 cases (control group) using CuT380A and under
      routine follow-up in our clinic. RESULTS: Ultrasonographic examination revealed
      IUD dislocation in 64% of 318 cases, whereas only 11% of the control group had
      dislocated IUDs. The difference between two groups was statistically significant.
      Especially in cases where the pregnancy group was less than 20 years old, IUD
      dislocations were recorded in 87.5%. The statistical analysis revealed a
      significant correlation in the distribution of IUD pregnancies according to
      years. When the demographic characteristics of two groups were compared, no
      statistically significant correlation was observed between the demographic
      characteristics and pregnancies with IUDs. There were 89 cases (27.9%) who
      decided on the continuation of IUD pregnancies. Unfortunately, 40% of these cases
      resulted in abortion. Only in 27% of 56 cases after IUD extraction because of IUD
      dislocation was miscarriage recorded. Meanwhile, 77% of the 26 cases with IUD
      left in the uterine cavity presented with miscarriage. Of the total of 36
      miscarriages, 33% were =6 weeks pregnancy, and 27% were over 10 weeks.
      CONCLUSION: IUD dislocation is a significant factor affecting IUD pregnancies.
      The fact that dislocation is most common in the first year reveals the necessity
      for more frequent controls in this period.

PMID- 16448958
TI  - Burden of concomitant allergic rhinitis in adults with asthma.
AB  - Asthma (A) and allergic rhinitis (AR) are common conditions with evidence of
      shared epidemiological and patho-physiological backgrounds. A systematic review
      of the literature in the last three decades was performed to summarize both the
      prevalence and the economic burden of concomitant AR in adult patients with
      asthma. The reported prevalence estimates of concomitant AR in patients with
      asthma in the United States and in Europe studies is in excess of 50%, with up to
      100% prevalence reported in patients with allergic asthma. In these populations,
      asthma-related medical resource use, including asthma attacks, emergency room
      visits, physician visits, and prescription medication use, is higher among
      asthmatic patients with concomitant AR compared to those without AR. These
      patients also experience more frequent absence from work and decreased
      productivity. A low prevalence (6.2%) of comorbid AR in people with asthma has
      been reported in a single study from Asia. A combined treatment strategy as
      recommended by international guidelines may improve asthma outcomes in asthmatic
      patients with concomitant AR.

PMID- 16448959
TI  - A library-site asthma education program for inner-city communities.
AB  - Asthma education programs are reportedly effective for children and adolescents.
      Urban and minority children continue to have poor asthma outcomes and limited
      access to asthma education programs. The purpose of this study was to determine
      whether a library-based asthma education program, the Columbus Ohio Partnership
      for Inner-City Asthma Education (COPICAE), offered to urban and minority children
      (with their parents) could improve asthma-related outcomes and reduce billing
      claims for asthma-related hospital visits. A prospective/observational study was
      conducted to evaluate asthma-related outcomes of 87 children who completed 6
      hours of asthma education using telephone follow-up at 12 and 24 months with a
      scored Living With Asthma Survey (LWAS). Hospital billing claims for asthma as
      the primary diagnosis were compared over a 24-month period for 64 children who
      completed 6 hours of asthma education with an age and zip code match control. Two
      separate focus groups with Spanish-speaking and English-speaking parents who
      completed 6 hours of asthma education with their children obtained parental
      perspectives about the asthma education classes. LWAS follow-up data were
      obtained on 67% of the participants at year 1 and 43% at year 2. Compared to pre
      intervention mean scores, there were decreases in scores to all LWAS items.
      Parents reported improvements in compliance with asthma medication use and
      overall control of their child's asthma. Parents also found the information from
      the asthma education classes to be "beneficial." Total asthma-related billing
      claims for children who completed 6 hours of asthma education decreased 63.2%,
      while those for age and zip code matched controls increased 0.7%. Inner-city and
      minority children (with their parents) who attended 6 hours of asthma education
      offered in a public library showed improvements in asthma-related outcomes over a
      24-month period and decreased billing claims for asthma-related hospital visits.
      Parents found 6 hours of asthma education to be beneficial in gaining basic
      knowledge about asthma and improving their child's illness control and self
      esteem in living with asthma.

PMID- 16448960
TI  - Feasibility of a national fatal asthma registry: more evidence of IRB variation
      in evaluation of a standard protocol.
AB  - PURPOSE: Approximately 4,500 Americans die from asthma each year. Our objective
      was to determine the feasibility of creating a national fatal asthma registry to
      better understand this problem.Methods. Using a standard questionnaire, 18 state
      vital statistics departments and 22 medical examiners offices were contacted in
      2001 to assess availability of fatal asthma data. Funding was obtained in 2002 to
      implement a fatal asthma registry. During 2003, the project was put on hold due
      to uncertainty about the impact of the Health Insurance Portability and
      Accountability Act (HIPAA). The project was revived in 2004 when a standard
      protocol was submitted to Institutional Review Boards (IRBs) in four different
      states. RESULTS: All vital statistics departments reported that they were able to
      identify the decedent's name and demographic characteristics. Contact information
      for a relative or doctor was available in all states. Demographic characteristics
      and autopsy findings were available from 100% of the medical examiners offices.
      However, IRBs at the four institutions required major protocol modifications,
      including language and approach for contacting next of kin. CONCLUSION:
      Availability of demographic and clinical data across states is consistent. The
      creation of a national fatal asthma registry appears feasible, but different IRB
      interpretations of what is permissible preclude a standard approach across
      states.

PMID- 16448961
TI  - Effect of age on bronchial reactivity in children with asthma.
AB  - In contrast to an abundance of data concerning age-related changes of bronchial
      sensitivity, the relationship between age and rapidity of bronchoconstriction
      (bronchial reactivity) remains unclear. We studied age and bronchial reactivity
      in children with asthma. Enrolled in this study were 511 asthmatic subjects and
      115 age-matched control subjects 1 to 16 years of age. Bronchial reactivity was
      represented by the slope of the methacholine transcutaneous oxygen pressure dose
      response curve (SPO(2)) in younger children and the slope of the respiratory
      resistance dose-response curve (SRrs) in older children. Overall, SPO(2) and SRrs
      were higher in asthmatic than control subjects. SPO(2) increased significantly
      from 1 to 6 years in asthmatic subjects, reaching a plateau after age 7. This age
      related change in SPO(2) also was seen in controls. SRrs in asthmatic subjects
      decreased after age 13, while SRrs in controls showed no significant change
      between age 7 and 16. Age-related change in bronchial reactivity occurs during
      childhood, possibly reflecting early changes in airway smooth muscle maturity and
      later changes in airway wall rigidity.

PMID- 16448962
TI  - Oral beta2-agonist use by preschool children with asthma in East and Central
      Harlem, New York.
AB  - Although studies have documented underuse of controller medications and overuse
      of short-acting inhaled ss(2)-agonist among children with persistent asthma in
      disadvantaged communities, the persistence of oral ss(2)-agonist use in pediatric
      practice has not been studied since inhaled short-acting ss(2)-agonists became
      widespread. We describe medications used to treat asthma among children 3 to 5
      years of age at 10 Head Start and other subsidized preschool centers in East and
      Central Harlem, New York City. We interviewed 149 parents/guardians of children
      who were identified as having probable asthma based on physician's diagnosis,
      persistent symptoms, hospitalization, and medication use. We classified 86 of the
      149 children (58%) as having current persistent asthma. Only 15 of them (17%)
      were reported to have used controller medications at least 5 days/week in the
      last 4 weeks-only 2 of whom used inhaled corticosteroids. By contrast, 53
      children (62%) used oral ss(2)-agonist in the last 4 weeks, often (72%) in
      conjunction with nebulized or inhaled short-acting ss(2)-agonist. Use of oral
      ss(2)-agonist was associated with more severe symptoms. This study documents the
      continued widespread use of oral ss(2)-agonist for treatment of children in a low
      income community with high prevalence of asthma.

PMID- 16448963
TI  - Predictors of early hospital readmission for asthma among inner-city children.
AB  - Factors associated with early asthma readmission have not been fully studied. To
      identify predictors of early readmission, we performed a matched case-control
      study of children discharged with primary diagnosis of asthma. Cases were
      readmitted with asthma within 30 days of discharge. Controls were not readmitted.
      Conditional logistic regression analysis was used. History of asthma
      hospitalization within the past 12 months was an independent predictor of early
      readmission (OR 1.89, p = 0.021). Modifiable factors such as medical treatment
      and management during and upon discharge from the index admission did not predict
      early asthma readmission.

PMID- 16448964
TI  - Asthma patients' assessments of health care and medical decision making: the role
      of health literacy.
AB  - The objectives of this cross-sectional study were to measure health literacy and
      its associations with asthma patients' assessments of care and their desire to
      participate in making decisions about their treatment. A total of 175 patients
      completed the Test of Functional Health Literacy in Adults and questions about
      satisfaction with asthma status, access to care, quality of care, and the desire
      to participate in treatment decisions. Patients' mean age was 42 years and 83%
      were women. Lower literacy was associated with less satisfaction with asthma
      status and worse assessment of quality of care received for asthma and other
      medical conditions (p < or = .005). Patients with lower literacy also were more
      likely not to want to participate in decisions about their care (OR .29, 95% CI
      .13, .65). These relationships persisted after controlling for demographic and
      asthma characteristics. These results provide additional incentives for
      physicians to find better ways to explain asthma treatments to low literacy
      patients.

PMID- 16448965
TI  - Increased diagnosis of asthma in hospitalized infants: the next target population
      for care management?
AB  - Hospitalization of children with asthma declined at our institution between 1996
      and 2000, before stabilizing for the past 5 years. The ages of children
      hospitalized since 2000 were examined to see if the demographics of the
      hospitalized population have changed to better understand why the hospitalization
      rate has remained the same despite continued, aggressive screening and education
      efforts. Data were gathered for our hospital through the Department of Defense
      Medical Health System Management Analysis and Reporting System (M2). The mean age
      (+/- SD) of children hospitalized in 2003 (2.84 +/- 2.53) was less than the mean
      age for 2000 and 2002 (4.85 +/- 3.7 and 4.61 +/- 4.45), respectively (p < 0.05),
      and more infants less than 2 years of age were hospitalized in 2003 (33/60, 55% p
      < 0.01) and 2004 (32/68, 47% p < 0.05) than in 2000 (19/70, 27%). The diagnosis
      of asthma in hospitalized infants and young children has increased over the past
      5 years, suggesting better recognition and providing a new target population for
      intervention with early asthma controller therapy.

PMID- 16448966
TI  - Impulse oscillometry is sensitive to bronchoconstriction after eucapnic voluntary
      hyperventilation or exercise.
AB  - Airway responses were compared following 6-minute eucapnic voluntary
      hyperventilation and 6-minute exercise challenges by examining resting and post
      challenge impulse oscillometry and spirometry variables. Twenty-two physically
      active individuals with probable exercise-induced bronchoconstriction took part
      in this study. Impulse oscillometry and spirometry were performed at baseline and
      for 20 minutes post-challenge at 5-minute intervals. High correlation was found
      between the two measures of change in airway function for both methods of
      challenge. Impulse oscillometry detected a difference in degree of response to
      the challenges, whereas spirometry indicated no difference, suggesting that
      impulse oscillometry is a more sensitive measure of change in airway function.

PMID- 16448967
TI  - Obesity and its relationship with asthma prevalence and severity in adolescents
      from southern Brazil.
AB  - Obesity has been pointed out as a risk factor for higher prevalence of asthma and
      asthma-related symptoms in adolescents. The objective was to evaluate the
      relationship between the prevalence of asthma and obesity in adolescents living
      in Santa Maria and surroundings (state of Rio Grande do Sul, southern Brazil),
      applying the International Study of Asthma and Allergies in Childhood (ISAAC)
      protocol. A total of 4,010 of 6,123 schoolchildren, 13 to 14 years of age,
      enrolled in the ISAAC phase III protocol (asthma core questionnaire) and were
      nutritionally evaluated: height, weight, and triceps skinfold (TSF) measurements.
      Prevalence of asthma (wheeze in the last 12 months) and prevalence of severe
      asthma (two or more affirmative responses to: more than 4 acute attacks of
      asthma, speech disturbance, sleep disturbance, wheezing with exercise) were
      evaluated and compared according to their nutritional status: obese and non
      obese. Obese adolescents were defined by body mass index (BMI, in kg/m(2)) > or
      =85th percentile and TSF > or =85th percentile. Obese and non-obese groups were
      compared for prevalence of asthma and asthma severity using the Chi-square test
      and odds ratio (OR) with 95% confidence interval. Analyzing all adolescents, we
      observed a significant positive relationship between the prevalence of obesity
      and affirmative responses to "wheeze ever" (OR = 1.28; 95% CI 1.08-1.52),
      "wheezing with exercise" (OR = 1.36; 95% CI 1.11-1.66), "asthma ever" (OR = 1.29;
      95% CI 1.03-1.62), and severe asthma (OR = 1.55; 95% CI 1.12-2.14). Among the
      boys, there was a significant positive association between obesity and "wheeze
      ever" (OR = 1.49; 95% CI 1.13-1.86). In girls, there was a significant positive
      relationship with "asthma ever" (OR = 1.38; 95% CI 1.01-1.88) and "wheezing with
      exercise" (OR = 1.36; 95% CI 1.11-1.66). This cross-sectional study with
      adolescents living in the southern region of Brazil showed that there is a
      positive association between obesity and prevalence of asthma symptoms and asthma
      severity, a finding mainly confined to girls.

PMID- 16448968
TI  - Family perceptions of the usual source of care among children with asthma by
      race/ethnicity, language, and family income.
AB  - A usual source of care (USC) can serve as the foundation for good primary health
      care and is critical for children living with a chronic health condition. This
      study applies national data to the following objectives: (1) describe family
      reports of the presence and characteristics of the USC for children with asthma;
      (2) examine evidence of systematic differences in the USC for these children with
      asthma by race/ethnicity, English language proficiency in Hispanic respondents,
      and family income; and (3) conduct multivariate analysis adjusting for possible
      confounding factors to examine independent effects of race/ethnicity, language,
      and income. Data from the 1996-2000 Medical Expenditure Panel Survey (MEPS) were
      analyzed. Overall, 95% of children with asthma had a USC, with Spanish-speaking
      Hispanics least likely to report a USC (89%). There were significant differences
      in USC attributes by race/ethnicity, language, and income, with the largest
      differences by type of provider and accessibility. Hispanics with poor English
      language proficiency had the greatest accessibility barriers.

PMID- 16448969
TI  - Determinants of bronchodilator responsiveness in patients with controlled asthma.
AB  - Short-term bronchodilator responsiveness to an inhaled ss 2 adrenergic agonist
      was assessed by changes in forced expiratory volume in 1 second (FEV(1)) in
      nonsmoking adults with controlled asthma (mild disease, 20 patients; moderate
      disease, 20 patients; severe disease, 18 patients). Responsiveness correlated
      significantly with age and with percent of predicted FEV(1) (%FEV(1)) except in
      patients with severe asthma, who showed significantly less responsiveness than
      others. Thus, responsiveness is closely associated with degree of airflow
      limitation in patients with controlled asthma and is significantly influenced by
      severity of disease and by aging.

PMID- 16448970
TI  - Misdiagnosis of COPD and asthma in primary care patients 40 years of age and
      over.
AB  - Chronic obstructive pulmonary disease (COPD) is often misdiagnosed as asthma,
      leading to inappropriate treatment and suboptimal patient outcomes. As part of a
      prospective study of patients with a history consistent with obstructive lung
      disease, we compared prior diagnostic labels with a study diagnosis based on
      spirometric results. We enrolled persons 40 years of age or older with prior
      diagnoses or medications consistent with obstructive lung disease. Patients were
      recruited via random mailing to primary care practices in Aberdeen, Scotland, and
      Denver, Colorado. Prior diagnoses of chronic bronchitis or emphysema (CBE) and
      asthma were reported by the subjects. Participants underwent pre- and post
      bronchodilator spirometry. A study diagnosis of COPD was defined using post
      bronchodilator forced expiratory volume in 1 second/forced vital capacity
      (FEV(1)/FVC) < 0.70. Spirometric examination was complete in 597 patients, of
      whom 235 (39.4%) had a study diagnosis of COPD. Among subjects with a spirometry
      based study diagnosis of COPD, 121 (51.5%) reported a prior diagnosis of asthma
      without concurrent CBE diagnosis, 89 (37.9%) reported a prior diagnosis of CBE,
      and 25 (10.6%) reported no prior diagnosis of obstructive lung disease. Despite
      the availability of consensus guideline diagnostic recommendations, diagnostic
      confusion between COPD and asthma appears common. Increased awareness of the
      differences between the two conditions is needed to promote optimal patient
      management and treatment.

PMID- 16448971
TI  - A population-based case-control study on the effect of bronchial asthma during
      pregnancy for congenital abnormalities of the offspring.
AB  - Bronchial asthma is one of the most common maternal diseases complicating
      pregnancy. We assessed the risks of congenital abnormalities in a case-control
      population-based analysis using the dataset of the Hungarian Case-Control
      Surveillance of Congenital Abnormalities between 1980 and 1996. Of the 22,843
      cases with congenital abnormalities, 511 (2.2%) had mothers with bronchial
      asthma, while of the 38,151 matched control subjects without congenital
      abnormalities 757 (2.0%) had mothers with bronchial asthma (unadjusted prevalence
      odds ratios [POR] 1.2; 95% CI: 1.0-1.3). In all mothers with bronchial asthma, a
      higher incidence of respiratory tract infections and higher drug intake could be
      observed. In the case group of medically recorded bronchial asthma, a slightly
      increased risk for club foot has been revealed. However, this weak association
      could be explained by the higher proportion of preterm births in this group. The
      main limitation of the analysis was that at the time of data collection only a
      small proportion of pregnant mothers were using anti-asthma medications
      recommended by the actual guidelines.

PMID- 16448972
TI  - The MMPI-2 Fake Bad Scale: concordance and specificity of true and estimated
      scores.
AB  - A number of recent studies have supported the use of the MMPI-2 Fake Bad Scale
      (FBS) as a measure of negative response bias, the scale at times demonstrating
      greater sensitivity to negative response bias than other MMPI-2 validity scales.
      However, clinicians may not always have access to True FBS (T-FBS) scores, such
      as when True-False answer sheets are unavailable or published research studies do
      not report FBS raw scores. Under these conditions, Larrabee (2003a) suggests a
      linear regression formula that provides estimated FBS (E-FBS) scores derived from
      weighted validity and clinical T-Scores. The present study intended to validate
      this regression formula of MMPI-2 E-FBS scores and demonstrate its specificity in
      a sample of non-litigating, clinically referred, medically intractable epilepsy
      patients. We predicted that the E-FBS scores would correlate highly (>.70) with
      the T-FBS scores, that the E-FBS would show comparable correlations with MMPI-2
      validity and clinical scales relative to the T-FBS, and that the E-FBS would show
      an adequate ability to match T-FBS scores using a variety of previously suggested
      T-FBS raw score cutoffs. Overall, E-FBS scores correlated very highly with T-FBS
      scores (r = .78, p < .0001), though correlations were especially high for women
      (r = .85, p < .0001) compared to men (r = .62, p < .001). Thirty-one of 32
      (96.9%) comparisons made between E-FBS/T-FBS correlates with other MMPI-2 scales
      were nonsignificant. When matching to T-FBS "high" and "low" scores, the E-FBS
      scores demonstrated the highest hit rate (92.5%) through use of Lees-Haley's
      (1992) revised cutoffs for men and women. These same cutoffs resulted in
      excellent overall specificity for both the T-FBS scores (92.5%) and E-FBS scores
      (90.6%). The authors conclude that the E-FBS represents an adequate estimate of T
      FBS scores in the current epilepsy sample. Use of E-FBS scores may be especially
      useful when clinicians conduct the MMPI-2 short form, which does not include all
      of the 43 FBS items but does include enough items to compute each of the validity
      and clinical T-Scores. Future studies should examine E-FBS sensitivity in
      compensation-seekers with incomplete effort.

PMID- 16448973
TI  - Visual attention deficits are associated with driving accidents in cognitively
      impaired HIV-infected individuals.
AB  - Previous research has found HIV-associated neuropsychological (NP) dysfunction to
      be associated with impaired driving skills. To determine whether specific
      impairments in visual attention impart an increased accident risk, we assessed 21
      HIV seronegative (HIV-) and 42 seropositive (HIV+) participants on NP tests and
      the Useful Field of View (UFOV), a computerized test of visual attention. HIV+
      participants performed significantly worse than the HIV- participants on the
      UFOV, particularly on the Divided Attention subtest. Poor UFOV performance was
      associated with higher accident rates in the past year, with a trend for NP
      impairment to also predict more accidents. The highest number of accidents
      occurred in the group with a "high risk" UFOV designation and NP impairment; this
      category correctly classified 93% of HIV+ participants as to who did, and did
      not, have an accident. Clinicians should attend to visual attention as well as
      general cognitive status in estimating which patients are at risk for impaired
      driving.

PMID- 16448974
TI  - The effect of recent stimulant use on sustained attention in HIV-infected adults.
AB  - Evidence suggests that stimulant use may exacerbate the deleterious cognitive
      effects of HIV, and that it has similar neuropathological consequences. In the
      current study, we examined the effect of recent stimulant use on sustained
      attention in adults infected with HIV. The sample consisted of 23 non-drug users
      and 17 stimulant users (cocaine and/or methamphetamine), all who were HIV
      positive. Drug use was determined via urine toxicology. Sustained attention was
      assessed with the Conners' Continuous Performance Task--second edition (CPT-II).
      Groups were compared on overall performance variables, as well as patterns of
      performance across time. Compared to the non-drug users, stimulant users showed a
      gradual increase in reaction time variability and omission errors. Stimulant
      users' scores indicated impaired vigilance relative to an age and gender-matched
      normative sample. The groups were equivalent on other measures of attention,
      global neuropsychological functioning, mood, and demographic variables. The
      results indicate that recent stimulant use among HIV-infected adults adversely
      affects sustained attention.

PMID- 16448975
TI  - Knowing "what" and knowing "when".
AB  - The ability to situate autobiographical memories accurately in the "time-line" of
      one's own life is a particular aspect of retrograde memory that has received
      little attention in well-controlled, systematic studies. Here, we addressed this
      issue by testing the hypothesis that patients with basal forebrain damage would
      be impaired in their ability to place various autobiographical memories
      accurately on a 'time-line' of their life. Seven such subjects were contrasted
      with 11 medial temporal lobe subjects, 8 brain-damaged comparison subjects, and
      18 normal comparison subjects, using a procedure in which subjects placed
      autobiographical events on a time-line of their life. The basal forebrain group
      was very impaired in this task, relative to the other groups, and on average,
      misplaced events by more than five years. Although the basal forebrain group was
      also impaired in retrieving the contents of autobiographical memory, they did not
      differ statistically from the medial temporal lobe group in this regard (and the
      medial temporal lobe group did not have impaired time placement of memories). The
      results indicate an intriguing dissociation between "knowing what" and "knowing
      when," and suggest that the basal forebrain contains structures that are
      especially important for "knowing when." Our findings are compatible with the
      view that the basal forebrain participates critically in retrieval strategies
      important for memory chronology, which contrasts with the medial temporal lobe's
      critical role in relational memory per se.

PMID- 16448976
TI  - Intraindividual variability as a marker of neurological dysfunction: a comparison
      of Alzheimer's disease and Parkinson's disease.
AB  - Individuals with certain neurological conditions may demonstrate greater
      inconsistency (i.e., intraindividual variability) on cognitive tasks compared to
      healthy controls. Several researchers have suggested that intraindividual
      variability may be a behavioral marker of compromised neurobiological mechanisms
      associated with aging, disease, or injury. The present study sought to
      investigate whether intraindividual variability is associated with general
      nervous system compromise, or rather, with certain types of neurological
      disturbances by comparing healthy adults, adults with Alzheimer's disease (AD),
      and Parkinson's disease (PD). Participants were assessed on four separate
      occasions using measures of reaction time and memory. Results indicated that
      inconsistency was correlated with indices of severity of impairment suggesting a
      dose-response relationship between cognitive disturbance and intraindividual
      variability: the more severe the cognitive disturbance, the greater the
      inconsistency. However, participants with AD were more inconsistent than those
      with PD, with both groups being more variable than the healthy group, even when
      controlling for group differences in overall severity of cognitive impairment or
      cognitive decline. Consequently, intraindividual variability may index both the
      severity of cognitive impairment and the nature of the neurological disturbance.

PMID- 16448977
TI  - Processing abilities associated with math skills in adult learning disability.
AB  - This study evaluated college adults (N = 138) referred for learning problems
      using a Cattell-Horn-Carroll based intelligence measure (Woodcock Johnson
      Revised: WJ-R) and spatial and executive function neuropsychological measures to
      determine processing abilities underlying math skills. Auditory and visual
      perceptual (WJ-R Ga and Gv), long- and short-memory (WJ-R Glr and Gsm),
      crystallized and fluid intellectual (WJ-R Gc and Gf), and spatial and executive
      function (Judgment of Line Orientation [JLO] and Category Test) measures
      differentiated those with and without math deficits. Multiple regression revealed
      selective processing abilities (Gf, JLO, and Category) predicting about 16% of
      the variance in math skills after variance associated with general intelligence
      (also about 16%) was removed. Cluster analysis found evidence for a selective
      spatial deficit group, a selective executive function deficit group and a double
      deficit (spatial and executive function) group. Results were discussed in
      relation to a double deficit hypothesis associated with developmental
      dyscalculia.

PMID- 16448978
TI  - Attention network dysfunction and treatment response of geriatric depression.
AB  - The Attention Network Test was used to assess the efficiency of the executive,
      orienting and vigilance attention networks and their association to treatment
      response in older patients with major depression. There were no significant
      performance differences between depressives and controls. However, within the
      depressed group, executive-related performance, but not orienting- or vigilance
      related performance was correlated with time to remission. The association of
      executive-attention network efficiency and antidepressant response provides the
      background for focused structural and functional neuroimaging studies aimed at
      identifying the functional neuroanatomy of antidepressant response.

PMID- 16448979
TI  - An "errorful" learning deficit in schizophrenia?
AB  - Disturbances in learning are prominent in schizophrenia. The present study
      examined the effect of committing mistakes (errors) on learning in schizophrenia.
      Subjects included schizophrenia and schizoaffective disorder patients (n = 36)
      and healthy adults (n = 22) who were administered a word-stem completion task
      under "errorfree" (no guessing) and "errorful" (guessing) conditions. The data
      were analyzed using a 2 (group) x 2 (order) x 2 (condition) repeated-measures
      ANOVA and by comparing standard residualized scores between patients and
      controls. The results from the ANOVA revealed a significant group x condition
      interaction with patients showing greater impairment relative to controls on the
      errorful versus errorfree condition. Similarly, contrasts of standard
      residualized scores revealed patients' scores on the errorful condition to be
      deviant from that of healthy adults. The findings implicate problems in the
      ability to self-correct and suggest that rehabilitation efforts incorporating
      errorless learning methods may benefit persons with schizophrenia.

PMID- 16448980
TI  - Psychological disturbance, incomplete effort, and compensation-seeking status as
      predictors of neuropsychological test performance in head injury.
AB  - Indices from the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) representing cognitive and
      emotional disturbance as well as incomplete effort on the Recognition Memory Test
      (RMT; Warrington, 1984) were examined as predictors of performance on the
      Halstead-Reitan Neuropsychological Test Battery (HRB; Reitan & Wolfson, 1993). In
      the current study, which included a large sample (N = 369) of patients referred
      for neuropsychological (NP) evaluation after presumptive head injury, MMPI-2
      measures of psychological disturbance accounted for as much as 25% of the
      variance in HRB test scores, resulting in a moderate overall effect size (median
      Adj. R(2) = .16; R = .40). When demographic variables, head injury severity, and
      compensation-seeking status were entered in previous steps, incomplete effort as
      defined by chance performance on the RMT accounted for between 2% and 13% of the
      variance in HRB test scores, with modest overall effect size (median R(2) Delta =
      .07; R = .26) in multiple regression equations. Additionally, when MMPI-2 indices
      of psychological disturbance were included in the last step, they accounted for
      2% to 11% of additional variance, retaining a modest overall effect (median R(2)
      Delta = .03; R = .17). Compensation-seeking status and injury severity as
      measured by duration of post-traumatic amnesia were, at best, modestly related to
      NP test performance. Findings confirm the reliable relationship between test
      performance and psychological disturbance as well as incomplete effort when
      assessing dysfunction following head injury. In contrast to previous studies,
      incomplete effort was unrelated to compensation-seeking status.

PMID- 16448981
TI  - An interactive test of serial behavior: age and practice alter executive
      function.
AB  - We describe an interactive, computer-based test inspired by the Trail Making Test
      (TMT). In this new test, young (mean age = 20.4 years) and older participants
      (mean age = 74.9 years) used natural, pointing responses to order series of
      numbers, letters, or intermixed letters and numbers. This interactive test, which
      avoids several deficiencies of TMT, assesses participants' baseline speed for
      detecting and responding to individual items, captures the time for each
      response, and segregates erroneous responses from correct ones. The inter
      response times with intermixed letters and numbers showed that participants did
      not always switch between the two different ordering tasks, but instead often
      recall letter-number pairs as single units. An additive factors analysis
      decomposed test times into functional components, including executive function,
      which took longer in older participants. With modest practice, both young and
      older participants sped up their ordering of intermixed numbers and letters,
      probably reflecting increased automaticity and reduced dependence upon executive
      function.

PMID- 16448982
TI  - Disruption of reflexive attention and eye movements in an individual with a
      collicular lesion.
AB  - The superior colliculus (SC) plays a central role in the control of saccadic eye
      movements and has also been implicated in control of covert spatial attention.
      While there is a growing body of evidence from studies of awake behaving primates
      that supports these proposals, direct evidence from humans has been sparse. In
      the present study we tested a patient with thiamine deficiency and a lesion of
      the SC, who performed both eye movement tasks (prosaccades and antisaccades, with
      or without a gap) and a covert spatial attention task assessing inhibition of
      return (IOR). For eye movements, the gap effect was disrupted, and abnormal
      saccade metrics occurred, with reflexive eye movements being disrupted moreso
      than voluntary eye movements. Each of these effects resolved coincident with
      thiamine treatment. The covert attention task revealed a complete absence of IOR.
      The unequal disruption of voluntary and reflexive eye movements supports the idea
      that oculomotor responses can be generated in an independent fashion by frontal
      cortical and lower level neural systems. The role of the SC and other structures
      in these orienting processes is discussed.

PMID- 16448983
TI  - Is apolipoprotein A5 a novel regulator of triglyceride-rich lipoproteins?
AB  - Hypertriglyceridemia is an independent risk factor for the development of
      cardiovascular disease and is often associated with diabetes, inflammation and
      the metabolic syndrome. Recently, apolipoprotein A5 (APOA5) was identified as a
      novel member of the APOA1/C3/A4 gene cluster. Data from mice over-expressing or
      lacking APOA5 provide direct evidence that this apolipoprotein plays a role in
      triglyceride metabolism. Moreover, plasma triglyceride levels were found to be
      strongly associated with APOA5 polymorphisms. The human APOA5 gene is regulated
      by transcription factors known to affect triglyceride metabolism such as PPARa,
      RORa, LXR and SREBP-1c and this supports its function. Insulin and interleukins
      regulate APOA5 gene expression and provide novel clues for the role of this
      apolipoprotein. To date, the triglyceride lowering action of apoA-V is attributed
      to the activation of lipoprotein lipase and an acceleration of very low density
      lipoprotein catabolism. Recent findings indicate that APOA5 could also influence
      cholesterol homeostasis and probably play a role in hypertriglyceridemia
      associated with diabetes and inflammation. This review aims to give a
      comprehensive summary of the current literature and supports the view that APOA5
      plays a relevant role in lipid metabolism.

PMID- 16448984
TI  - Molecular mechanisms of RET-induced Hirschsprung pathogenesis.
AB  - The RET proto-oncogene is the major gene involved in the pathogenesis of
      Hirschsprung (HSCR), a complex genetic disease characterized by lack of ganglia
      along variable lengths of the gut. Here we present a survey of the different
      molecular mechanisms through which RET mutations lead to the disease development.
      Among these, loss of function, gain of function, apoptosis, aberrant splicing and
      decreased gene expression are exemplified and considered with respect to their
      pathogenetic impact. In particular, RET transcription regulation represents a new
      insight into the outline of HSCR susceptibility, and having reached important
      progress in the last few years, deserves to be reviewed. Notably, gene expression
      impairment seems to be at the basis of the association of HSCR disease with
      several RET polymorphisms, allowing us to define a predisposing haplotype
      spanning from the promoter to exon 2. Putative functional variants, in the
      promoter and in intron 1, and proposed as low penetrant predisposing alleles, are
      presented and discussed. Finally, based on the RET mutation effects thus
      summarized, we attempt to derive conclusions which may be useful for HSCR risk
      prediction and genetic counselling.

PMID- 16448985
TI  - Hemophagocytic lymphohistiocytosis: diagnosis, pathophysiology, treatment, and
      future perspectives.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease in
      which the immune system becomes overactive due to its inability to effectively
      respond to infections and/or shut down the immune response to such infections.
      The discovery of genetic defects in the secretory pathway of natural killer (NK)
      cells and cytotoxic T cells in some patients with this disease has raised
      important questions of the role of cytotoxic cells in the control of infections
      and in immune regulation. This review will give a brief overview of the clinical
      presentation and accepted treatment of HLH. Furthermore, it will give an in-depth
      review into the known genetic defects and current knowledge of the
      pathophysiology of this disorder, and will highlight recent evidence suggesting
      that cytotoxic defects in CD4+ T regulatory cells may contribute to the
      pathogenesis of HLH.

PMID- 16448986
TI  - Metabolic syndrome: to be or not to be?

PMID- 16448987
TI  - How to best define the metabolic syndrome.
AB  - The constellation of metabolic abnormalities including centrally distributed
      obesity, decreased high-density lipoprotein cholesterol (HDL-C), elevated
      triglycerides, elevated blood pressure (BP), and hyperglycaemia is known as the
      metabolic syndrome. Associated with increased risk of both type 2 diabetes and
      cardiovascular disease (CVD), the metabolic syndrome is thought to be a driver of
      the modern day epidemics of diabetes and CVD and has become a major public health
      challenge around the world 1. Since its initial description, several definitions
      of the syndrome have emerged. Each of these definitions used differing sets of
      criteria, the combination of which either reflected contrasting views on
      pathogenic mechanisms or clinical usefulness. The use of these definitions to
      conduct research into the metabolic syndrome in diverse populations resulted in
      wide ranging prevalence rates, inconsistencies and confusion, and spurred on the
      vigorous debate regarding how the metabolic syndrome should be defined. In
      response to this controversy, the International Diabetes Federation (IDF) has
      recently proposed a new definition, which is applicable to populations around the
      world 12. It is envisaged that the development of the new definition for the
      metabolic syndrome will help resolve the confusion caused by the number of
      earlier attempts to define this important entity.

PMID- 16448988
TI  - Is insulin resistance the cause of the metabolic syndrome?
AB  - Following up on original descriptions of clustering of cardiovascular risk
      factors (chiefly, glucose intolerance, dyslipidaemia and hypertension) around the
      presence of insulin resistance, the metabolic syndrome has recently been upgraded
      to the status of a disease entity with an inherent predictive value for
      cardiovascular disease. In pathophysiological terms, insulin resistance (of
      glucose metabolism) and the attendant compensatory hyperinsulinaemia are causally
      related to each of glucose intolerance, dyslipidaemia, high blood pressure and
      vascular dysfunction. The physiological mechanisms are concisely reviewed here.
      However, insulin resistance/hyperinsulinaemia alone is insufficient to cause
      these abnormalities, for which other pathogenic factors (e.g. ss-cell dysfunction
      for glucose intolerance) are required. The metabolic syndrome, on the other hand,
      has evolved from a set of statistical associations believed to carry an excess of
      cardiovascular risk. In the various existing definitions, a mixture of physical,
      metabolic and clinical variables have been used on grounds of predictive value or
      practical ease. These variables belong to different phenotypes, which are
      upstream, intermediate and proximal, respectively, in their relation to clinical
      disease. The resulting 'syndromes' usually lack a cogent conceptual structure,
      may reflect the particular data set from which they are extracted and may be of
      limited applicability. While overt diabetes, clinical hypertension and frank
      dyslipidaemia are often present together in the same patient, a subclinical
      syndrome with a distinct, probable aetiology and a proven power as a risk
      indicator remains to be identified.

PMID- 16448989
TI  - Is visceral obesity the cause of the metabolic syndrome?
AB  - Despite the fact that controversy remains around the underlying
      pathophysiological processes leading to the development of the metabolic syndrome
      (insulin resistance and/or hyperinsulinemia versus abdominal obesity), there is
      increased recognition that abdominal obesity is the most prevalent form of the
      metabolic syndrome. Although it has been well established that there is a greater
      prevalence of chronic metabolic diseases such as diabetes and cardiovascular
      diseases in obese patients than among normal weight individuals, obesity is a
      remarkably heterogeneous condition and not every obese patient is characterized
      by co-morbidities. In this regard, body fat distribution, especially visceral
      adipose tissue accumulation, has been found to be a major correlate of a cluster
      of diabetogenic, atherogenic, prothrombotic and proinflammatory metabolic
      abnormalities referred to as the metabolic syndrome. Due to its anatomic location
      and peculiar metabolic, hyperlipolytic activity, the expanded visceral adipose
      depot is a key correlate of the altered cardiometabolic risk profile observed
      among individuals with a high-risk abdominal obesity phenotype. Evidence suggests
      that this dysmetabolic profile is predictive of a substantially increased risk of
      coronary heart disease even in the absence of classical risk factors. Finally, a
      moderate weight loss in initially abdominally obese patients is associated with a
      preferential mobilization of visceral adipose tissue, which in turn leads to
      substantial improvements in the metabolic risk profile predictive of a reduced
      risk of coronary heart disease and of type 2 diabetes.

PMID- 16448990
TI  - The metabolic syndrome and cardiovascular disease.
AB  - The metabolic syndrome, which is very common in the general population, is
      defined by the clustering of several classic cardiovascular risk factors, such as
      type 2 diabetes, hypertension, high triglycerides and low high-density
      lipoprotein cholesterol (HDL). Central obesity and insulin resistance, which are
      the two underlying disorders of the syndrome, are further risk factors for
      cardiovascular disease. Moreover, a panel of novel (non-traditional) risk factors
      are ancillary features of the metabolic syndrome. They include biomarkers of
      chronic mild inflammation (e.g. C-reactive protein, CRP), increased oxidant
      stress (e.g. oxidized low density lipoprotein, LDL), thrombophilia (e.g.
      plasminogen activator inhibitor-1, PAI-1) and endothelial dysfunction (e.g. E
      selectin). Therefore, subjects with the metabolic syndrome are potentially at
      high risk of developing atherosclerosis and clinical cardiovascular events.In
      recent years several longitudinal studies have confirmed that subjects with the
      metabolic syndrome present with atherosclerosis and suffer from myocardial
      infarction and stroke at rates higher than subjects without the syndrome. The
      risk of cardiovascular disease (CVD) is particularly high in women with the
      syndrome and in subjects with pre-existing diabetes, CVD and/or high CRP.
      However, an increased risk is already present in subjects with a cluster of
      multiple mild abnormalities. The risk related to the metabolic syndrome is
      definitely higher when subjects affected are compared to subjects free of any
      metabolic abnormality.

PMID- 16448991
TI  - PCI in ST-elevation infarction -- one flew over the cuckoo's nest.

PMID- 16448992
TI  - Does smoking cessation improve quality of life in patients with coronary heart
      disease?
AB  - OBJECTIVE: To evaluate whether smoking cessation after a coronary event improves
      quality of life, and to assess whether quality of life is a predictor of smoking
      cessation. DESIGN: Health-related quality of life at baseline and at 12 months
      follow up were measured in a randomised smoking cessation trial of 240 smokers
      aged under 76 years admitted for myocardial infarction, unstable angina or
      coronary bypass surgery. At 12 months follow up 101 had managed to give up
      smoking (quitters), and 117 were smokers (sustained smokers). RESULTS: The
      quitters and sustained smokers had similar improvements in all quality of life
      domains from baseline to 12 months follow up. Further, after adjustment for
      differences in baseline characteristics, the quality of life was not
      significantly different in the quitters compared to the sustained smokers neither
      at baseline nor at 12 months follow up. CONCLUSIONS: Smoking cessation did not
      improve quality of life compared to sustained smoking after a coronary event in a
      12 month follow up. Quality of life was not a significant predictor of smoking
      cessation.

PMID- 16448993
TI  - Cost-effectiveness of the Taxus paclitaxel-eluting stent in the Swedish
      healthcare system.
AB  - OBJECTIVE: To analyse the cost-effectiveness of Taxus compared to a bare-metal
      stent in patients with coronary artery disease in the Swedish healthcare setting.
      DESIGN: A decision-analytic model combining clinical data on revascularization
      rates with Swedish unit costs for medical resources and utility data from the
      literature. RESULTS: For patients of moderate risk, the average cost per patient
      at 12 months is 72,200 SEK for Taxus and 66,900 SEK for a bare-metal stent, while
      the average cost for high risk patients is nearly equivalent (73,000 vs. 71,700
      SEK). The cost per revascularization avoided is generally favourable, while the
      incremental cost per QALY gained varies depending on the assumptions made; from
      2,351,000 SEK for patients of moderate risk at 12-months to cost saving at 24
      months for high risk patients. Budget impact scenarios at 12 months are cost
      neutral. CONCLUSION: The Taxus stent is cost-effective in high risk patients,
      particularly at 24 months. Although it may be less cost-effective for the general
      population, there is still a substantial offset of initial procedure costs
      through lower rate of repeat revascularizations.

PMID- 16448994
TI  - Coronary artery bypass grafting within the first year after treatment of large
      acute myocardial infarctions with angioplasty or fibrinolysis.
AB  - OBJECTIVES: To calculate the incidence and analyse and outcome after coronary
      artery bypass grafting (CABG) within the first year after randomisation of 1,572
      patients with acute myocardial infarctions with ST-segment elevation (STEMI) to
      either percutaneous coronary intervention (PCI) or fibrinolysis. DESIGN: The
      study includes 131 patients: 108 male and 23 female with a mean age 62 years.
      RESULTS: The total 30-day mortality after CABG was 4.6% (7.5% in the PCI group
      and 2.6% in the fibrinolysis group). The 30-day mortality was 9.8% after CABG
      within the first 30-days and 1.3% after CABG within 31-365 days. The patients who
      were operated early had a reduced EF to 43% as compared to 50% in patients who
      were not operated or patients having CABG after 30-days (p=0.002). CONCLUSION:
      CABG was performed within the first year after STEMI in 10% of patients
      randomised to fibrinolysis and in 6.7% of patients randomised to PCI. Patients
      having CABG within the first 30-days after treatment of STEMI had an increased
      mortality of 9.8%.

PMID- 16448995
TI  - Health-related quality of life three years after coronary surgery: a comparison
      with the general population.
AB  - OBJECTIVES: To assess health-related quality of life (HRQOL) in patients three
      years after coronary artery bypass grafting (CABG) compared to the general
      Norwegian population, with emphasis on age and gender-differences. DESIGN: A
      cross-sectional postal survey of patients who underwent CABG in 2000. HRQOL was
      assessed using the Short Form 36 (SF-36). Subgroup analyses were performed
      according to age (<70 versus =70 years) and gender. RESULTS: Of 233 eligible
      patients 203 responded (mean age 67.6 years, 17% females). Patients reported
      better scores on bodily pain than the general population (p=0.008), but did not
      differ on other subscales of SF-36. Younger patients tended to score lower, older
      patients higher than the general population on HRQOL. Female patients reported
      lower HRQOL than the general female population and reported significantly lower
      scores than male patients on 3 of 8 subscales. CONCLUSIONS: Three years after
      CABG the HRQOL is comparable to the general Norwegian population even in older
      patients. The older patients reported less pain than the general population.

PMID- 16448996
TI  - Sustained anti-beta-adrenergic effect of melatonin in guinea pig heart papillary
      muscle.
AB  - OBJECTIVE: Anti-ss-adrenergic actions of several substances influence heart
      function significantly. The anti-ss-adrenergic effect of melatonin was
      investigated, with special attention to protein kinase C (PKC) and nitric oxide
      (NO). DESIGN: Guinea pig papillary muscles were exposed to melatonin (500 pM) for
      15 min and 20 min washout. Contractile force was measured during a bolus of
      isoproterenol (300 nM) given before melatonin, at the end of melatonin-exposure
      and after washout. In separate experiments blockers of PKC, NO-synthase (NOS) and
      melatonin receptors were added, or forskolin (10 microM) substituted for
      isoproterenol. RESULTS: Melatonin significantly reduced the increase in
      contractile force in response to isoproterenol, both when present and after
      melatonin-washout. The reduction was unaffected by inhibition of PKC, while
      inhibition of melatonin receptors or NOS seemed to abolish the effect. Melatonin
      induced a sustained but not acute reduction of contractile force response with
      forskolin stimulation. This was abolished by NOS-inhibition. CONCLUSION: Receptor
      mediated immediate and sustained anti-ss-adrenergic effects of melatonin were
      demonstrated in contractile function. A role for NO in the response was
      indicated, while a role for PKC was not verified.

PMID- 16448997
TI  - Inflammatory response and platelet activation after off-pump coronary artery
      bypass surgery.
AB  - BACKGROUND: Cardiac surgery induces a systemic inflammatory activation and
      alterations in the hemostatic cascade. The responses contribute to postoperative
      complications but may also have protective effects. We investigated the
      relationship between inflammation, hemostasis and bleeding after off-pump
      coronary artery bypass surgery (OPCAB). METHODS: Ten OPCAB patients were included
      in a prospective descriptive study. Selected markers of inflammation (IL-6, IL-8,
      PMN-elastase, C3a, and SC5b-9), and hemostasis (platelet count, ss
      thromboglobulin, anti-thrombin, D-dimer and fibrinogen) were measured before and
      immediately after surgery. Postoperative bleeding was registered. RESULTS:
      Inflammatory variables did not alter significantly during surgery while ss
      thromboglobulin concentrations increased and anti-thrombin and fibrinogen
      decreased. There were significant postoperative correlations between PMN-elastase
      and ss-thromboglobulin (r=0.82, p=0.004), between PMN-elastase and fibrinogen
      (r=0.69, p=0.03) and between C3a and ss-thromboglobulin (r=0.71, p=0.02). In
      addition, there were significant inverse correlations between postoperative
      bleeding and pre- and postoperative fibrinogen levels (r=-0.76, p=0.011 and r=
      0.84, p=0.002 respectively), between bleeding and postoperative ss
      thromboglobulin levels (r=-0.66, p=0.04) and between bleeding and postoperative
      PMN-elastase (r=-0.75, p=0.01). CONCLUSIONS: The results give further evidence
      for an association between the inflammatory response and hemostasis after cardiac
      surgery.

PMID- 16448998
TI  - Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Ten
      years experience in Denmark.
AB  - OBJECTIVES: To evaluate survival and functional outcome in patients treated by
      pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension
      in Denmark. DESIGN: Follow-up of the first 50 patients operated at Aarhus
      University Hospital, Denmark. RESULTS: Fifty patients underwent PEA in the period
      from 1994 to mid 2004. Prior to surgery all patients were in World Health
      Organization (WHO) function class III (n=33) or IV (n=17). The mean pulmonary
      artery pressure was 50 mmHg (range 25-76), cardiac index 1.8 l min(-1)m(-2)
      (range 0.8-2.8) and pulmonary vascular resistance 819 dyn s cm(-5) (range 241
      3,067). In-hospital mortality was 12/50 (24%). Surgical mortality was highest in
      the early period. Since year 2000 in-hospital deaths occurred in only 2 among 23
      patients (9%). Leading causes of death were persistent pulmonary hypertension and
      bleeding. Three patients died during long-term follow-up with a median
      observation time of 3 years. The overall 5 year survival rate was 74%. At 3
      months follow-up 90% of the patients (34/38) had improved one or more WHO
      functional classes and the systolic pulmonary artery pressure estimated by
      Doppler echocardiography had decreased from 80 mmHg (range 49-115) to 43 mmHg
      (range 14-95). CONCLUSION: Pulmonary endarterectomy has been successfully
      implemented in Denmark. The perioperative mortality was reduced over time to 9%
      during the past 5 years. Functional outcome and long-term survival were excellent
      stressing the importance of surgical treatment for chronic thromboembolic
      pulmonary hypertension.

PMID- 16448999
TI  - Mean arterial pressure about 40 mmHg during CPB is associated with cerebral
      ischemia in piglets.
AB  - OBJECTIVE: To investigate if a mean arterial pressure below 50 mmHg during CPB
      may lead to cerebral ischemia. MATERIAL AND METHODS: Piglets with low mean
      arterial pressure by nitroprusside (LP-group) (n=6) were compared with piglets
      given norepinephrine to obtain high pressure (HP-group) (n=6) during normothermic
      and hypothermic CPB. Intracranial pressure, flow and markers of cerebral energy
      metabolism (microdialysis) were recorded. RESULTS: Mean arterial pressure
      differed significantly between the groups and stabilized about 40-45 mmHg in the
      LP-group. Cerebral perfusion pressure decreased to 21.3 (7.7) mmHg in the LP
      group and increased to 51.8 (11.2) mmHg in the HP-group at 150 min of CPB
      (P<0.001, between groups). During bypass the intracerebral glucose concentration
      decreased significantly in the LP-group. In this group the lactate/pyruvate ratio
      increased from 15.5 (5.3) to 64.5 (87.6) at 90 min and 45.0 (36.5) at 150 min
      (P<0.05) with no such changes in the HP-group. Similarly the cerebral glycerol
      concentration increased significantly in the LP-group, whereas glycerol remained
      stable in the HP-group. CONCLUSION: Mean arterial pressure about 40 mmHg during
      CPB is associated with cerebral ischemia.

PMID- 16449000
TI  - Long-term beneficial effects of dexamethasone on intellectual and
      neuropsychological outcome of children with pneumococcal meningitis.
AB  - A Substantial ratio of bacterial meningitis survivors suffers mild or serious
      intellectual and neuropsychological handicaps. We organized eighty subjects into
      three groups: 1) Pneumococcal meningitis (PM) who did not receive dexamethasone,
      2) PM who received dexamethasone, 3) Other bacterial meningitis with different
      etiology. All subjects underwent Bender Visual Motor Gestalt test and age
      appropriate Intelligence quotient (IQ) tests. The mean full-scale IQ scoring fell
      within normal range (90+/-17) in the post-meningitic cohort. There was no
      statistical difference between two pneumococcal groups regarding full scale IQ
      testing (88+/-16 and 91+/-18) and Bender-Gestalt scoring (4.0+/-3.3 and 3.8+/
      2.6), respectively. However, the subjects with full scale IQ score <85 (below the
      average) were statistically less in the group with steroid therapy. PM patients
      who received dexamethasone therapy had statistically better academic performance.
      As a result, adjuvant steroid therapy has no significant impact on overall
      intellectual tests in PM subjects. However, dexamethasone seems to diminish
      development of below the average IQ scoring in PM cases. In addition, PM subjects
      who received steroids showed better academic achievement. These findings may
      support the idea of dexamethasone administration prior to first antibiotic dose
      in PM subjects.

PMID- 16449001
TI  - Should we continue using amphotericin B deoxycholate for the treatment of fungal
      infections? Adverse events and clinical outcomes.
AB  - Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is
      associated with high adverse event and mortality rates. A retrospective review
      was undertaken to describe adverse events and clinical outcomes in adult patients
      with IFI treated with only AmBd as initial therapy.

PMID- 16449002
TI  - Sub-acute neuropathy in patients with African tick bite fever.
AB  - African tick bite fever (ATBF) caused by Rickettsia africae is an emerging health
      problem in travellers to sub-Saharan Africa. We here present 6 patients with
      evidence of long-lasting sub-acute neuropathy following ATBF contracted during
      safari trips to southern Africa. Three patients developed radiating pain,
      paresthaesia and/or motor weakness of extremities, 2 had hemi-facial pain and
      paresthaesia, and 1 developed unilateral sensorineural hearing loss. When
      evaluated 3-26 months after symptom onset, cerebrospinal fluid samples from 5
      patients were negative for R. africae PCR and serology, but revealed elevated
      protein content in 3 and mild pleocytosis in 1 case. Despite extensive
      investigations, no plausible alternative causes of neuropathy could be
      identified. Treatment with doxycycline in 2 patients had no clinical effect.
      Given the current increase of international safari tourism to sub-Saharan Africa,
      more cases of sub-acute neuropathy following ATBF may well be encountered in
      Europe and elsewhere in the y to come.

PMID- 16449003
TI  - Dynamics of proviral HIV-1 184M/V in circulating CD4+ T-cells: a 90 days follow
      up study after initiation/switch of HAART.
AB  - HIV-1 viral load falls rapidly on initiation of HAART. This phase of decreasing
      yet substantial viral production in the presence of antiretroviral drugs could
      generate resistant HIV-1. Whether switching a drug from a failing regime changes
      the demography of the mutations associated with it in the CD4+ T-cell compartment
      is not well-defined. We investigated the presence/absence and quantity of 184M
      and 184V in the CD4+ T-cell compartment of naive patients initiated to HAART
      (group I), and patients who shifted to a non-lamivudine therapy (group II). We
      initiated a prospective 90 d follow-up study of 11 patients to detect and
      quantity proviral HIV-1 184M and 184V in the CD4+ T-cell compartment with a
      sensitive real time PCR assay. Results showed that the 184V was not detected in
      the CD4+ T-cell compartment of any of the 7 naive patients who started on HAART.
      Three out of the 4 patients in group II experienced a fall in the percentage of
      184V, with reduction to below detection limits in 2 patients. It can be concluded
      that initiation of HAART does not allow the archiving of the lamivudine
      associated mutation, 184V, in the CD4+ T-cell compartment. Reduction in the
      quantity of 184V when therapy is switched to an effective non-lamivudine regime
      indicates that the mutation in this compartment is dynamic.

PMID- 16449004
TI  - Graves' disease during immune reconstitution in HIV-infected patients treated
      with HAART.
AB  - Autoimmune phenomena after immune recovery due to HAART are not frequently
      described. Recently we found 3 patients with Graves' disease after starting
      HAART, outnumbering the expected incidence; 13 patients have been reported in the
      literature up to the present time.A probable relation between immune restoration
      and development of Graves' disease might be suspected.

PMID- 16449005
TI  - Bartonella quintana associated neuroretinitis.
AB  - We report an observational case of Bartonella quintana-associated neuroretinitis.
      The patient had a positive IgM IFA titer for Bartonella quintana early in the
      disease. After treatment, the neuroretinitis and IgM resolved. Given the
      patient's history, symptoms, response to treatment, and IgM course, we believe
      his neuroretinitis was secondary to Bartonella quintana.

PMID- 16449006
TI  - Chest wall soft tissue tuberculosis: a protracted course over a 10-year period.

PMID- 16449007
TI  - A case of Staphylococcus aureus endocarditis after ear piercing in a patient with
      normal cardiac valve and a questionnaire survey on adverse events of body
      piercing in college students of Korea.
AB  - Body piercing in young adults is on the rise in western countries and also in
      Korea. It is usually practised by non-medical persons, and therefore frequently
      entails local adverse events. Serious complications, such as septic arthritis or
      infective endocarditis, are occasionally reported, but infective endocarditis in
      patients with normal cardiac valve is rare. We experienced a case of acute S.
      aureus endocarditis after ear piercing. Thereafter we studied the status and
      complications of body piercing in college students of Korea based on a
      questionnaire survey, and revealed that the rate of ear piercing is high (96.5%)
      and 61.3% of the pierced persons experience local complications.

PMID- 16449008
TI  - Daptomycin-rifampin for a recurrent MRSA joint infection unresponsive to
      vancomycin-based therapy.
AB  - A 54-y-old morbidly obese male presented with methicillin-resistant
      Staphylococcus aureus (MRSA) bacteremia secondary to chronic right hip
      arthroplasty infection. Bacteremia persisted despite prolonged vancomycin-based
      therapy (MIC < or = 1 microg/ml) and prosthetic removal. Adding daptomycin
      rifampin resolved bacteremia within 48 h; hip cultures remained negative post
      discharge. This case describes alternative treatment for chronic MRSA infections.

PMID- 16449009
TI  - Does steroid exposure adversely affect the outcome of subacute bacterial
      endocarditis? Report of two cases.
AB  - Multivalvular endocarditis of native cardiac valves due to streptococci in
      patients without any predisposing conditions has not been reported previously.
      Moreover, the effect of exposure to systemic steroids on the outcome of subacute
      bacterial endocarditis (SBE) is not well known. We describe 2 patients with SBE
      involving 3 native cardiac valves, who were initially exposed to systemic steroid
      therapy under the clinical impression of 'rheumatologic disorders'.

PMID- 16449010
TI  - Septic shock caused by Streptococcus pneumoniae in a post-splenectomy patient
      successfully treated with recombinant human activated protein C.
AB  - We present a case of severe sepsis due to Streptococcus pneumoniae, serotype 22F
      treated with recombinant human activated protein C (drotrecogin alpha activated)
      (DrotAA). APACHE II score at admission was 34 with a predicted mortality of 81%.
      A wide range of cytokines, chemokines and receptors was measured before and after
      DrotAA treatment. Soon after infusion of 24 microg DrotAA per kg bodyweight and h
      (microg/kg/h) over a period of 96 h, cytokine levels fell markedly. The patient
      survived and was discharged after 6 weeks of hospitalization. In conclusion,
      administration of DrotAA in a case of Streptococcus pneumoniae-induced septic
      shock was followed by dramatic changes in serum levels of immuno-regulatory
      cytokines.

PMID- 16449011
TI  - Purulent pericarditis caused by Neisseria meningitidis serogroup C and confirmed
      through polymerase chain reaction.
AB  - We here report the case of a previously healthy 20-y-old male with disseminated
      meningococcal disease and purulent pericarditis. Polymerase chain reaction was
      used to identify Neisseria meningitidis serogroup C as the causative agent in the
      pericardial fluid.

PMID- 16449012
TI  - Micrococcus sedentarius bacteraemia presenting with haemophagocytic syndrome in
      previously healthy boy.
AB  - Haemophagocytic syndromes are the clinical manifestation of an increased
      macrophagic activity with haemophagocytosis. Infection-associated HS was
      originally described by Risdall in 1979, in viral disease. Since the initial
      description HS has also been documented in patients with bacterial, parasitic or
      fungal infections. We describe a case of Micrococcus sedentarius bacteraemia in a
      previously healthy 10-y-old boy with haemophagocytic syndrome. Species of
      micrococci are generally considered as non-pathogenic commensals that colonize
      the skin, mucosae and oropharynx. We report the first case of Microccoccus
      sedentarius bacteraemia in an immunocompetent host and first case of HS
      associated with Micrococcus species.

PMID- 16449013
TI  - Mycobacterium marinum, a further infectious agent associated with sarcoidosis:
      the polyetiology hypothesis.
AB  - A 39-y-old male had a diagnosis of sarcoidosis and corticosteroid therapy was
      started. Surprisingly, following his discharge from hospital, Mycobacterium
      marinum was isolated in 1 of 3 sputum samples taken 7 weeks earlier on admission.
      After this, Mycobacterium marinum-DNA was identified in the stored lung biopsies
      by the PCR-RFLP of the hsp65 gene.

PMID- 16449014
TI  - Successful treatment of visceral leishmaniasis with fluconazole and allopurinol
      in a patient with renal failure.
AB  - Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and
      pentamidine) pose several problems. Failure of antimonials or severe toxicity is
      particularly troublesome in patients with renal insufficiency. We report a case
      of visceral leishmaniasis and renal insufficiency successfully treated with
      fluconazole and allopurinol for 4 months.

PMID- 16449015
TI  - Influenza A and Influenza B virus infections in the same season: how unlucky can
      a bone marrow transplant recipient be?

PMID- 16449016
TI  - Nobel Prizes in paediatrics: Santiago Ramon y Cajal (1852-1934) and the founding
      of neuroembryology.

PMID- 16449017
TI  - The true cause of pyloric stenosis is hyperacidity.
AB  - Pyloric stenosis (PS) has no known cause. A testable theory of cause is proposed,
      based on the inheritance of a parietal cell mass (PCM) at the upper end of the
      normal range. It is proposed that, until 3-4 wk of age, the obligatory high
      fasting gastrins are at maximal levels and not able to be diminished by
      increasing antral acidity. Hence, rising acidity is not reduced by a lowered
      gastrin during this time, and very high acidity occurs. CONCLUSION: Persisting
      duodenal hyperacidity is created by an inherited high PCM and loss of gastrin
      control. These two factors produce pyloric stenosis through work hypertrophy from
      repeated pyloric contraction in response to hyperacidity.

PMID- 16449018
TI  - Does inadequate maternal iron or DHA status have a negative impact on an infant's
      functional outcomes?
AB  - Marginal intake of iron and omega-3 long-chain fatty acids (DHA) is prevalent
      among pregnant women. It is not clear to what extent poor iron or DHA status
      during pregnancy impacts on an infant's functional outcomes. A few studies
      suggest that inadequate maternal iron or DHA status may be associated with
      suboptimal functional outcomes in infants. In addition, there is a lack of
      prospective studies using randomized, double-blind design or experimental studies
      with appropriate animal models. Although both nutrients are involved in early
      brain development and their metabolism is interrelated, no study has examined the
      interaction between iron and omega-3 fatty acids during pregnancy. CONCLUSION:
      Long-term studies on large cohorts of pregnant women and their infants are needed
      to determine whether inadequate iron or DHA status during pregnancy is
      detrimental to infant neurodevelopment.

PMID- 16449019
TI  - Effects of brief exposure to water, breast-milk substitutes, or other liquids on
      the success and duration of breastfeeding: a systematic review.
AB  - AIM: To systematically evaluate the effect of supplemental fluids or feedings
      during the first days of life on the overall breastfeeding duration and rate of
      exclusive breastfeeding among healthy infants. METHODS: Medical subject headings
      and free-language terms were used to search the following electronic databases
      for studies relevant to breastfeeding: MEDLINE, EMBASE, Cumulative Index to
      Nursing and Allied Health (CINAHL), the Cochrane Library, and La Leche League.
      Only randomized, controlled trials (RCT) were considered for study inclusion.
      RESULTS: Of 56 potentially relevant clinical trials identified, only one RCT (170
      infants) met the inclusion criteria for this systematic review. In this study,
      formula feeding was significantly more frequent at 4 wk in the experimental group
      in which breastfeeding had been supplemented with 5% glucose ad libitum during
      the first 3 d of life (n = 83) than in the exclusively breastfed control group (n
      = 87) (p < 0.05). At 16 wk (5 mo postpartum), the percentage of mothers who
      continued breastfeeding, either exclusively or partially, was significantly lower
      in the experimental group than in the control group (p < 0.01). CONCLUSION: There
      remains considerable uncertainty about the effect of brief exposure to water,
      breast-milk substitutes, or other liquids on the success and duration of
      breastfeeding.

PMID- 16449020
TI  - Influence of early postnatal nutritional management on oxidative stress and
      antioxidant defence in extreme prematurity.
AB  - The increased survival of infants born at mid-gestation in the last decade is
      associated with significant oxygen free radical-mediated morbidities.
      Resuscitation with 100% oxygen, oxidant load from parenteral nutrition fluids,
      and oxidant stress inherent to the systemic inflammatory state subsequent to
      infection and tissue injury are all contributory. CONCLUSION: Improving early
      postnatal protein nutrition and the formulation of parenteral nutrition fluids
      would potentially reduce the oxidative stress and enhance the antioxidant defence
      of extremely premature newborns.

PMID- 16449021
TI  - 8-hydroxy-2-desoxyguanosine serum concentrations as a marker of DNA damage in
      patients with classical galactosaemia.
AB  - BACKGROUND: Classical galactosaemia is caused by a deficiency of galactose-1
      phosphate uridyl transferase, resulting in high galactose (Gal), galactose-1
      phosphate (Gal-1-P) and galactitol blood levels. Galactose/lactose restriction
      intake is the only treatment. 8-hydroxy-2-desoxyguanosine (8-OHdG) is a marker of
      oxidized DNA damage. AIM: Since galactosaemia outcome is closely related to
      restriction of Gal intake, we aimed to evaluate correlations between Gal-1-P,
      total antioxidant status (TAS) and 8-OHdG blood levels in galactosaemic patients
      on poor or strict diet. METHODS: Venous blood samples were obtained from
      galactosaemic patients (n = 11) on poor diet (group A) and after 30 d on strict
      diet (group B). Twenty-eight healthy children were the controls. Gal-1-P and TAS
      were evaluated in their blood spectrophotometrically and 8-OHdG with an
      immunoassay. RESULTS: TAS was significantly decreased (905 +/- 112 micromol/l) in
      patients on a "loose diet" (group A) as compared to those when restored to their
      diet (group B) (1,340 +/- 112 micromol/l, p < 0.001) and controls (1,558 +/- 115
      micromol/l, p < 0.001). As expected, Gal-1-P levels were remarkably increased in
      group A. 8-OHdG level was twofold higher (0.25 +/- 0.03 ng/ml) in group A than
      that of group B (0.11 +/- 0.04 ng/ml) and threefold higher than that of the
      controls (0.08 +/- 0.02 ng/ml). TAS and Gal-1-P inversely correlated to 8-OHdG
      (r= -0.802, p < 0.001), whereas Gal-1-P positively correlated to 8-OHdG (r =
      0.820, p < 0.001) in all the groups. CONCLUSION: a) Low TAS and high Gal-1-P
      levels are implicated with high 8-OHdG blood levels in galactosaemic patients; b)
      8-OHdG may be a sensitive biomarker of DNA damage in patients with classical
      galactosaemia.

PMID- 16449022
TI  - Genetic factors and clinical significance of acanthosis nigricans in obese
      Japanese children and adolescents.
AB  - AIM: To clarify the clinical significance of acanthosis nigricans (AN) and the
      association of gene polymorphisms in the ss2- and ss3-adrenergic receptors (B2ADR
      and B3ADR) in Japanese obese children and adolescents. METHODS: Seventy obese
      subjects (56 boys, 14 girls) from 5 to 19 y of age were examined as to clinical
      features. Genetic analyses were performed in 83 obese subjects (61 boys, 22
      girls), 2 to 17 y of age. Typing of gene polymorphisms in B2ADR and B3ADR was
      achieved by polymerase chain reaction (PCR) of genomic DNA and restriction
      fragment-length polymorphism analysis (PCR-RFLP). RESULTS: The group with AN (n =
      30) had higher values for percent overweight, BMI, waist circumference, fasting
      insulin, HOMA-R, leptin and PAI-1 than the AN-negative group (n = 40), but there
      were no significant differences in age, sex or percent body fat between the two
      groups. The prevalences of B2ADR Gly16 and B3ADR Arg64 were significantly higher
      in AN-positive (n = 26) than in AN-negative (n = 57) subjects. In addition, the
      AN frequency was significantly higher in the group with both Gly16 and Arg64 than
      in the group with neither of these alleles (55.6% vs 12.5%, p < 0.05).
      CONCLUSION: We demonstrate that AN is a useful clinical marker for the severity
      of obesity associated with a high BMI, and that B2ADR Gly16 and B3ADR Arg64 are
      associated synergistically with AN in obese children and adolescents.

PMID- 16449023
TI  - Oral ranitidine and duration of gastric pH >4.0 in infants with persisting reflux
      symptoms.
AB  - BACKGROUND: Ranitidine is a drug commonly used in pathological gastro-oesophageal
      reflux (GOR) in infants. Non-responsiveness has been reported. Data regarding the
      effect of ranitidine on oesophageal acid exposure and reduction of gastric acid
      secretion are limited in this age group. OBJECTIVE: To evaluate oesophageal acid
      exposure, reduction of gastric acid secretion and histology of oesophageal
      biopsies in infants who clinically do not respond to oral ranitidine. PATIENTS
      AND DESIGN: 103 infants (mean age 3.3 +/- 1.8 mo) with persisting symptoms of
      reflux despite administration of ranitidine, prescribed previously by a referring
      physician, at a mean (SD) dose of 9.4 (+/- 3.3) mg/kg/d for at least 2 wk (mean
      30 d), were submitted to a 24-h pH study and oesophageal biopsy (90/103
      patients). RESULTS: Histological oesophagitis was present in 21/90 (23%). The
      oesophageal reflux index (RI) was >5% and >10% in 21/103 (20%) and 6/103 (6%)
      infants, respectively. Gastric pH was >4.0 during <50%, >50%, >75% and >90% of
      the duration of pH monitoring in 33/103 (32%), 70/103 (68%), 22/103 (21%) and
      7/103 (7%), respectively. By simple regression analysis, the dosage of ranitidine
      correlated with the oesophageal RI (r = 0.21; p = 0.05), but not with the
      duration of time gastric pH was >4.0 (r = 0.09; p = 0.39). Histological
      oesophagitis did not correlate with ranitidine dosage, duration of treatment,
      duration gastric pH was >4.0 and oesophageal reflux index. CONCLUSION: Some
      infants presenting with symptoms assumed to be GOR and acid related fail to
      respond to acid suppression with ranitidine, either because they need better acid
      suppression or because the symptoms are not acid related.

PMID- 16449024
TI  - Nontuberculous mycobacterial adenitis: effectiveness of chemotherapy following
      incomplete excision.
AB  - BACKGROUND: Management of lymphadenopathy caused by nontuberculous mycobacteria
      (NTM) is primarily surgical. Where this cannot achieve sufficient clearance of
      infected nodes, chemotherapy is often given. AIM: This study compared results of
      surgery alone with surgery followed by chemotherapy in instances where there was
      incomplete surgical removal of diseased tissue. METHODS: Chemotherapy comprised
      azithromycin 10 mg/kg and rifabutin 6 mg/kg both given once daily for 6 mo.
      Ninety-eight children with NTM infection were seen in the period 1990-2004. Sixty
      eight cases with adenopathy where "time to healing" (discharge stopped and
      inflammation settled) was known were available to compare response to treatment.
      RESULTS: The median (range) "time to healing" in weeks for 43 patients who had
      surgery alone was: incision and drainage (I&D)/curettage 6 (1-72) (n = 10);
      excision 3 (1-28) (n = 22); and from the last operation of multiple (repeat)
      surgery 3 (1-40) (n = 11). For 25 patients who required chemotherapy in addition
      to surgery, the median (range) "time to healing" in weeks was I&D/curettage 10 (1
      40) (n = 17), excision 14 (8-20) (n = 2) and multiple surgery 29 (2-88) (n = 6).
      CONCLUSION: In children with adenitis due to NTM, where surgical resection is
      followed by continued discharge and inflammation, chemotherapy should be
      considered before further surgery is undertaken.

PMID- 16449025
TI  - Risk factors associated with the need for additional intravenous gamma-globulin
      therapy for Kawasaki disease.
AB  - AIM: To investigate the characteristics of patients with Kawasaki disease who
      needed intravenous gamma-globulin (IVGG) re-treatment. METHODS: Using the
      database of the 17th nationwide survey in Japan, a total 11,366 patients were
      identified and analysed (1,855 re-treatment patients and 9,511 responders).
      RESULTS: Multivariate logistic regression analysis showed that male sex (odds
      ratio (OR) 1.26; 95% CI 1.14-1.40), complete cases (OR 1.39; 95% CI 1.07-1.80),
      recurrence (OR 1.47; 95% CI 1.15-1.88), IVGG treatment within 4 d of illness (OR
      2.05; 95% CI 1.84-2.27), daily dose of initial IVGG less than 1,000 mg/Kg (OR
      0.54; 95% CI 0.48-0.61), exanthema (OR 2.03; 95% CI 1.62-2.56), lips and oral
      lesions (OR 1.57; 95% CI 1.24-1.98), peripheral extremities changes (OR 1.85; 95%
      CI 1.54-2.22), and cervical lymphadenopathy (OR 1.89; 95% CI 1.66-2.16) were
      independent risk factors associated with the need for IVGG re-treatment.
      CONCLUSION: Male sex, recurrence, and treatment with IVGG at a dose of 1,000 mg/d
      or less within 4 d of illness onset are independent risk factors associated with
      the need for IVGG re-treatment.

PMID- 16449026
TI  - Body mass index references for Turkish children.
AB  - AIM: To construct the body mass index reference curves for Turkish children aged
      6 to 18 y, and to determine the prevalence of overweight and obesity. SUBJECTS
      AND METHODS: Height and weight measurements of healthy schoolchildren (1,100
      boys, 1,019 girls) were obtained biannually. Body mass index was calculated from
      11,648 height and weight measurements. Centile curves were constructed using the
      LMS method. RESULTS: The smoothed percentile values and curves for body mass
      index in Turkish children show that there is a constant increase in body mass
      index values towards adulthood, especially during the pubertal years, in both
      sexes. The prevalence of overweight is 25% and obesity 4% in boys at age 18 y.
      The percentage of overweight and obesity in girls at age 14 was 15% and 1%,
      respectively. The sample size was too small to come to any conclusion regarding
      these rates at 18 y of age. CONCLUSION: This study presents data and curves for
      body mass index values in healthy Turkish children aged 6 to 18 y. The values are
      in compliance with those of Western countries.

PMID- 16449027
TI  - Absence of hypoglycemia in response to varying doses of recombinant human insulin
      like growth factor-I (rhIGF-I) in children and adolescents with low serum
      concentrations of IGF-I.
AB  - AIM: To determine whether recombinant human insulin-like growth factor-I (rhIGF
      I) administration to children with low IGF-I and relatively low insulin-like
      growth factor binding protein-3 (IGFBP3) serum concentrations would result in
      hypoglycemia. METHODS: Eighteen children age 11-19 y with serum levels of IGF-I< 
      2 SDS and IGFBP3< 0 SDS were randomly assigned to receive rhIGF-I at 80 microg/kg
      body weight daily (n = 6), 40 microg/kg twice daily (n = 6), or 80 microg/kg
      twice daily (n = 6). After a 10-d dose escalation and 15 d of treatment at the
      specified dosage, a 25-h pharmacokinetic/pharmacodynamic profile was obtained,
      which included 22 blood glucose measurements. Regular meals and snacks were
      provided. RESULTS: No signs or symptoms of hypoglycemia were noted throughout the
      study. There were no differences in mean blood glucose concentrations among the
      three dosage groups. The lowest glucose value recorded, 3.44 mmol/l, was 15 min
      after a morning injection of 80 microg/kg IGF-I, and promptly rose. Although
      subjects were selected on the basis of low concentrations of IGF-I to represent
      proposed candidates for rhIGF-I therapy, the mean and range of SDS for height
      were not different from those of previously studied normal Ecuadorian controls.
      CONCLUSION: In normal individuals with low serum concentrations of IGF-I and
      relatively low concentrations of IGFBP3, the administration of therapeutic doses
      of rhIGF-I, while maintaining reasonable food intake, does not result in
      hypoglycemia.

PMID- 16449028
TI  - Oral aphthous ulcers and dental enamel defects in children with coeliac disease.
AB  - AIM: Coeliac disease is characterized by oral manifestations, such as dental
      enamel defects and recurrent oral aphthae. In this study we compared the
      prevalence of enamel defects and recurrent aphthous stomatitis (RAS) between
      patients diagnosed with coeliac disease and healthy controls. METHODS: A total of
      72 patients with coeliac disease were studied together with 162 normal healthy
      subjects as controls to individualize the prevalence of enamel defects and
      recurrent aphthous stomatitis (RAS) in this disease. RESULTS: Dental enamel
      defects were found in 14/70 (20%) coeliac patients and in 9/159 (5.6%) controls.
      In particular, 13/53 (24.5%) coeliac patients with mixed or permanent dentition
      and 1/17 (5.8%) coeliac children with deciduous dentition had enamel defects.
      Altogether, 9/145 (6.2%) control subjects with mixed or permanent dentition had
      dental enamel defects. None of the controls with deciduous dentition had enamel
      defects. Thus, the enamel defects occurred more frequently in coeliac patients (p
      < 0.001). Regarding RAS, 24/72 (33.3%) coeliac patients and 38/162 (23.4%)
      control subjects had aphthous ulcers. Statistically significant differences were
      not observed between the two groups (p > 0.05). One in three coeliac subjects
      suffering from RAS received benefit from a gluten-free diet. CONCLUSION: In the
      present study, the prevalence of enamel defects was found to be greater in
      coeliac patients than healthy controls. Even though the prevalence of RAS in
      coeliac subjects varied from healthy controls, the difference was not
      statistically significant. However, more than 1/3 coeliac subjects suffering from
      RAS benefited from a gluten-free diet.

PMID- 16449029
TI  - Children with chronic conditions in a paediatric emergency department.
AB  - AIM: To describe the use of a paediatric emergency department by children with
      chronic conditions. MATERIAL AND METHODS: We prospectively indexed all the
      children seen in our emergency department during 1 y to describe the population
      of children with chronic conditions, and to compare it with the general
      paediatric population. RESULTS: There were 11,483 patient visits, of which 11%
      were by chronically ill children. Six subspeciality areas accounted for the vast
      majority of the chronic conditions seen: neurology (30%), cardiology (18%),
      pulmonology (18%), nephro-urology (16%), haemato-oncology (9%) and endocrinology
      (4%). Admission rate to the hospital was significantly higher for chronically ill
      patients (38% vs 23%). Among chief complaints, fever, respiratory distress,
      headache and seizures were overrepresented in chronically ill children. The chief
      complaint was related to the child's chronic condition in 51% of the visits. In
      both chronically and non-chronically ill patients, the majority of final
      diagnoses were related to infection (57% and 65%, respectively). Among diagnoses,
      bacterial infections, seizures, vasovagal syncopes and asthma were
      overrepresented in chronically ill children. CONCLUSION: From the analysis of our
      data, we conclude that children with chronic conditions account for a tenth of
      all visits to a paediatric emergency department. The paediatric emergency
      physicians provide an important service to both the children with chronic
      conditions and the subspecialists who care for them.

PMID- 16449030
TI  - Ototoxic drugs and sensorineural hearing loss following severe neonatal
      respiratory failure.
AB  - AIM: To determine relationships between ototoxic drugs and 4-y sensorineural
      hearing loss (SNHL) in near-term and term survivors of severe neonatal
      respiratory failure. METHODS: All 81 survivors of the Canadian arm of the
      Neonatal Inhaled Nitric Oxide Study (mortality 32, loss to follow-up 9) received
      loop diuretics, aminoglycosides, and neuromuscular blockers (NMB), and 50
      received vancomycin as neonates. Prospective, longitudinal secondary outcome
      using audiological tests diagnosed late-onset, progressive SNHL in 43 (53%); not
      flat (sloping) in 29, flat (severe to profound) in 14. Risk for SNHL was
      determined. RESULTS: A combination of duration of diuretic use of >14 d and
      average NMB dose of >0.96 mg/kg/d contributed to SNHL among survivors (odds ratio
      5.2; 95% CI 1.6, 16.7). Markers of illness severity did not contribute. Dosage or
      duration of aminoglycosides use did not relate to SNHL. Cumulative dosages and
      duration of use of diuretics; NMB; use of vancomycin; and overlap of diuretics
      with NMB, aminoglycosides, and vancomycin individually linked to SNHL (p<0.001).
      CONCLUSION: Overuse of loop diuretics and/or NMB contributes to SNHL after
      neonatal respiratory failure; markers of illness severity or the appropriate
      administration of aminoglycosides do not.

PMID- 16449031
TI  - Very-low-birthweight and term small-for-gestational-age adolescents: attention
      revisited.
AB  - AIM: To assess whether adolescents with very low birthweight (VLBW) and peers
      born small for gestational age (SGA) at term are at a disadvantage when attending
      to or executing tasks. METHODS: Cohorts of 54 VLBW (<or=1,500 g), 60 SGA and 83
      controls were tested with the Knox Cube Test, Conners' Continuous Performance
      Test (CPT II), Stroop Colour-Word Test, Trail Making Test (TMT) A & B, and
      Wisconsin Card Sorting Test (WCST). IQ was estimated using the subtests
      vocabulary and picture arrangement of WISC III. RESULTS: VLBW adolescents scored
      worse than controls on Knox Cube Test, Stroop Colour-Word Test, TMT A & B and
      WCST, whereas term SGA adolescents only made more non-perseverative errors in
      WCST and more errors in the interference condition of the Stroop Colour-Word
      Test. Thirty-two (38.6%) adolescents in the control group had poor performance (<
      2 SD) on at least one of the tests compared with 40 (74.1%) VLBW (p<0.01) and 32
      (53.3%) SGA adolescents (not significant). CONCLUSION: VLBW adolescents are at
      risk of disadvantage in aspects of attention and/or executive functions. The
      adverse effects of being born SGA at term appear to be few in these domains of
      cognitive function.

PMID- 16449032
TI  - Maternal signs of chorioamnionitis: persistent cognitive impairment in low
      birthweight children.
AB  - AIM: To examine whether chorioamnionitis (CA) is associated with long-term
      cognitive impairment in low-birthweight (LBW) children without major handicaps
      such as cerebral palsy. METHODS: Population-based long-term follow-up study at 11
      y of age of 130 LBW children with birthweight less than 2,000 g, without major
      handicaps. Thirteen children with maternal signs of clinical CA were compared
      with the 117 LBW children without. Main outcome measure was psychometric
      intelligence, assessed using four subscales from the Norwegian version of the
      Wechsler Intelligence Scale for Children -- Revised. RESULTS: Mean performance IQ
      for the LBW children with maternal signs of CA (89, SD 13) was significantly
      lower compared to the other LBW children (98, SD 16) at 11 y of age (difference
      of mean 10, 95% CI of difference 0.4 to 19, p=0.04). CONCLUSION: Maternal
      chorioamnionitis, known to be associated with an increased frequency of cerebral
      palsy, may have lasting negative consequences for fetal brain development,
      resulting in long-term cognitive impairments, even when major handicaps such as
      cerebral palsy are absent.

PMID- 16449033
TI  - Elevation of serum creatine kinase in response to medical treatment of Graves'
      disease in children.
AB  - We describe two cases of increases in serum creatine kinase (CK) concentrations
      in children undergoing treatment of Graves' disease with antithyroid medications.
      Presenting complaints consisted of myalgias and muscle cramping in both patients,
      and increases in serum CK levels were noted 1 mo after initiation of antithyroid
      drugs. Both patients were euthyroid at the time of CK elevation. While the
      mechanisms for this process are not clear, it is likely that the acute decrease
      of thyroid hormones in tissues following a state of chronic hyperthyroidism may
      result in relative hypothyroid states and subsequent alterations in CK
      concentrations. CONCLUSION: Although this side effect has been reported in
      adults, it is a novel finding in children. Clinicians should be aware of the rare
      potential for elevations in serum CK when initiating treatment for Graves'
      disease in children.

PMID- 16449034
TI  - Anakinra therapy for CINCA syndrome with a novel mutation in exon 4 of the CIAS1
      gene.
AB  - We report on a patient with chronic infantile neurological cutaneous and
      articular (CINCA) syndrome. Sequence analysis revealed a novel missense mutation
      in exon 4 of the CIAS1 gene. The patient was unresponsive to several treatments
      including prednisolone, immunosuppressants (azathioprine and cyclosporin),
      disease-modifying antirheumatic drugs (DMARDs: penicillamine, salazopyrin and
      methotrexate) and the tumour necrosis factor-alpha (TNF-a)-blocker infliximab. At
      32 mo of age, administration of the recombinant human interleukin-1 receptor
      antagonist anakinra commenced, which caused an immediate and marked improvement
      in the clinical symptoms and laboratory test results. Continuous inhibition of
      the inflammation required a dose of 1.0 mg/kg every 12 h. CONCLUSION: Following
      the diagnosis of CINCA syndrome, anakinra treatment should be commenced as the
      first line of therapy.

PMID- 16449036
TI  - Perforation of an inguinoscrotal Littre's hernia due to Meckel's diverticulitis:
      an unusual cause of acute hemiscrotum.

PMID- 16449035
TI  - Small bowel intussusception in a very-low-birthweight infant.

PMID- 16449037
TI  - Violence against women: a global public health crisis.

PMID- 16449038
TI  - Fertility in Norwegian women: results from a population-based health survey.
AB  - AIMS: Reproductive behaviour has changed during the most recent decades, with
      increased infertility and subfertility. This study evaluated fertility, estimated
      the prevalence of fertility problems, and assessed possible predictors for
      impaired fertility. METHODS: Eligible subjects were 9,983 menopausal women
      participating in two health surveys. Data were collected by comprehensive
      questionnaires. RESULTS: Of all women 89.3% were fertile, 4.8% were subfertile,
      4.1% were voluntarily childless, and 1.8% were involuntaruly childless. Impaired
      fertility was associated with a higher level of education and excessive alcohol
      intake. There were significant differences in subfertility among the parous
      women, with increased subfertility with decreasing age. Among the nullipara,
      involuntary childlessness was more prevalent in the youngest age group, while
      voluntary childlessness increased with advancing age. CONCLUSIONS: Fertility
      problems were quite common, and have increased in younger age groups, though
      seemingly fewer women remained childless past their reproductive age in the
      youngest age group.

PMID- 16449039
TI  - Use of oral contraceptives and mortality during 14 years' follow-up of Norwegian
      women.
AB  - AIMS: The aim was to evaluate total and cardiovascular disease (CVD) mortality in
      relation to use of oral contraceptives (OC) in a cohort of women with a
      relatively high prevalence of smoking and high serum lipid levels. METHODS: In
      all 29,053 women aged 20-49 years were invited to a health survey in 1985-88. Of
      the total 82% attended and 20,282 women free of known CVD were included in this
      analysis. The relative risk (RR) of mortality during 14 years of follow-up was
      compared between OC users and non-users by means of proportional hazards
      regression. RESULTS: About 50% of 827 OC users were daily cigarette smokers, and
      the mean total cholesterol level in the cohort was 5.9 mmol/l. There were 518
      deaths, of which 10 occurred among the women taking OC at baseline. Of three
      deaths from CVD among OC users, two occurred in the first year of follow-up.
      Among non-smokers using OC three women died during the follow-up; none of the
      deaths was due to CVD. Women using OC of any type had no different adjusted total
      mortality (RR 0.87; 95% CI 0.46-1.65) or CVD mortality (RR 1.41; 95% CI 0.44
      4.56) compared with non-users. CONCLUSIONS: The results were consistent with
      previous evidence which does not indicate that mortality from all causes or CVD
      is elevated in women using OC.

PMID- 16449040
TI  - Macro-organizational factors, the incidence of work disability, and work ability
      among the total workforce of home care workers in Sweden.
AB  - AIMS: To investigate the importance of macro-organizational factors, i.e.
      organizational sociodemographic and socioeconomic preconditions, of the municipal
      incidence of long-term sick leave, disability pension, and prevalence of workers
      with long-term work ability among home care workers. METHODS: In an ecological
      study design, data from national databases were combined by record linkage.
      Descriptive and analytical statistics were used to estimate and interpret macro
      organizational factors (economic resources, region, unemployment, employment,
      occupational rehabilitation, return to work, age structures of inhabitants and
      home care workers). RESULTS: The incidence of long-term sick leave among female
      home care workers was twice as high as that of male home care workers, and
      incidence of disability pension was about four times as high for the women. A
      great variation in municipal incidence of long-term sick leave, disability
      pension, and long-term work ability (101-264, 0.6-19.6, and 913-1,279 per 1,000
      full-time equivalent workers and year) was also found. The strongest single
      factor for long-term work ability was a high proportion of part-time or hourly
      paid employees, which explained 35% of the municipal variation. Macro
      organizational factors explained long-term work ability (47-62% explained
      variance) better than long-term sick leave (33% explained variance). There was a
      low rehabilitation activity; only 2% received occupational rehabilitation and 5%
      of those on sick leave longer than 2 weeks returned to work within 30 days.
      CONCLUSIONS: The differences in the municipal proportion of work ability
      incidence indicate a preventive potential, especially related to employment and
      return to work after sick leave.

PMID- 16449041
TI  - Refining a probabilistic model for interpreting verbal autopsy data.
AB  - OBJECTIVE: To build on the previously reported development of a Bayesian
      probabilistic model for interpreting verbal autopsy (VA) data, attempting to
      improve the model's performance in determining cause of death and to reassess it.
      DESIGN: An expert group of clinicians, coming from a wide range geographically
      and in terms of specialization, was convened. Over a four-day period the content
      of the previous probabilistic model was reviewed in detail and adjusted as
      necessary to reflect the group consensus. The revised model was tested with the
      same 189 VA cases from Vietnam, assessed by two local clinicians, that were used
      to test the preliminary model. RESULTS: The revised model contained a total of
      104 indicators that could be derived from VA data and 34 possible causes of
      death. When applied to the 189 Vietnamese cases, 142 (75.1%) achieved concordance
      between the model's output and the previous clinical consensus. The remaining 47
      cases (24.9%) were presented to a further independent clinician for reassessment.
      As a result, consensus between clinical reassessment and the model's output was
      achieved in 28 cases (14.8%); clinical reassessment and the original clinical
      opinion agreed in 8 cases (4.2%), and in the remaining 11 cases (5.8%) clinical
      reassessment, the model, and the original clinical opinion all differed. Thus
      overall the model was considered to have performed well in 170 cases (89.9%).
      CONCLUSIONS: This approach to interpreting VA data continues to show promise. The
      next steps will be to evaluate it against other sources of VA data. The expert
      group approach to determining the required probability base seems to have been a
      productive one in improving the performance of the model.

PMID- 16449042
TI  - Health behaviour among adolescents in Denmark: influence of school class and
      individual risk factors.
AB  - AIMS: The aim of this study was to assess the relative influence of school class
      on health behaviour among adolescents versus that of the family's socioeconomic
      status and individual factors among adolescents. METHODS: The material comprised
      3,458 students in grades 8 and 9 in 244 school classes. Data were collected
      through questionnaires completed by the students and by their class teacher and
      information from the school physician. Multilevel analysis was used to indicate
      the relative significance of individual and school class characteristics.
      RESULTS: We find no consistent pattern between the mother's socioeconomic status
      and the included health behaviour measurements; however, adolescents from the
      lower socioeconomic groups had a higher risk of unhealthy dietary habits and
      adolescents whose mothers were unemployed had a significantly lower risk of
      drinking alcohol weekly versus all other adolescents. Not living with both
      biological parents, focusing on friends, and not being very academically
      proficient were associated with an increased risk of harmful health behaviour.
      Health behaviour varied substantially between school classes, especially for
      daily smoking, weekly alcohol consumption, and use of hashish and other
      euphoriants. Circumstances in the school class more profoundly influenced risk
      behaviour among adolescents (smoking, alcohol consumption, and use of hashish or
      other euphoriants) than their dietary habits (eating breakfast, frequent intake
      of fruit and vegetables, and frequent intake of soft drinks). CONCLUSIONS: The
      school class had the relatively strongest influence on adolescents' risk
      behaviour (smoking, alcohol intake, and use of hashish or other euphoriants),
      whereas family circumstances comprised the strongest influence on dietary habits.

PMID- 16449043
TI  - Neighborhood social participation, use of anxiolytic-hypnotic drugs, and women's
      propensity for disability pension: a multilevel analysis.
AB  - AIMS: The increasing number of people on disability pension in Sweden is of
      concern for Swedish policy-makers, and there is a need for a better understanding
      of the mechanisms behind disability pension. We investigated (i) whether women
      living in the same neighborhood have a similar propensity for disability pension
      that relates to neighborhood social participation, and (ii) whether there is an
      association between anxiolytic-hypnotic drug (AHD) use and disability pension in
      women that is modified by the neighborhood context. METHODS: We used multilevel
      logistic regression with 12,156 women aged 45 to 64 (first level) residing in 95
      neighborhoods (second level) in the city of Malmo (250,000 inhabitants), Sweden,
      who participated in the Malmo Diet and Cancer Study (1991-96). RESULTS: Both AHD
      use (OR = 2.09, 95% CI 1.65, 2.65) and neighborhood rate of low social
      participation (OR = 11.85, 95% CI 5.09, 27.58) were associated with higher
      propensity for disability pension. The interval odds ratio indicated that the
      influence of neighborhood social participation was large compared with the
      unexplained variance between the neighborhoods. The association between AHD use
      and disability pension was not modified by the neighborhood context. The median
      odds ratio was 1.44 after adjusting for individual characteristics and 1.27 after
      the additional adjusting for neighborhood social participation. CONCLUSIONS:
      Women living in the same neighborhood appear to have a similar propensity for
      disability pension, beyond individual characteristics, and this contextual effect
      seems largely explained by neighborhood social participation. In addition, AHD
      use might increase the propensity for disability pension in women.

PMID- 16449044
TI  - Burnout among employees in human service work: design and baseline findings of
      the PUMA study.
AB  - AIM: To present the theoretical framework, design, methods, and baseline findings
      of the first Danish study on determinants and consequences of burnout, and the
      impact of workplace interventions in human service work organizations. METHOD: A
      5-year prospective intervention study comprising 2,391 employees from different
      organizations in the human service sector: social security offices, psychiatric
      prison, institutions for severely disabled, hospitals, and homecare services.
      Data were collected at baseline and at two follow-ups. The authors developed a
      new burnout tool (the Copenhagen Burnout Inventory) covering work-related, client
      related, and personal burnout. The study includes potential determinants of
      burnout (e.g. the psychosocial work environment, social relations outside work,
      lifestyle factors, and personality aspects) and consequences of burnout (e.g.
      poor health, low job satisfaction, turnover, and absenteeism). Here, the focus is
      on the description of the study population at baseline, including associations of
      work burnout with psychosocial work environment scales and absence. RESULTS:
      Response rate at baseline was 80.1%. Midwives and homecare workers had high
      levels on both work- and client-related burnout. Prison officers had the highest
      level on client-related burnout. Supervisors and office assistants had low levels
      on both scales. Work burnout showed the highest correlations with job
      satisfaction (r = -0.51), quantitative demands (r = 0.48), role-conflicts (r =
      0.44), and emotional demands (r = 0.42). Sickness absence was 13.9 vs 6.0 days
      among participants in the highest and lowest work burnout quartile, respectively.
      CONCLUSION: The findings indicate that study design and methods are adequate for
      the upcoming prospective analyses of aetiology and consequences of burnout and of
      the impact of workplace interventions.

PMID- 16449045
TI  - Can gender differences in psychosocial factors be explained by socioeconomic
      status?
AB  - AIMS: The aims of this study were to examine (1) if associations between gender
      and psychosocial factors could be explained by socioeconomic status (SES) and (2)
      if associations between gender and psychosocial factors are more salient at lower
      levels of SES. METHODS: Psychosocial factors such as decision latitude and social
      integration were studied in a cross-sectional study in two steps. In a public
      health survey, 4,086 randomly selected men and women aged 30-64 participated. Of
      these, 257 men and women also participated in an in-depth study. SES was measured
      in terms of education and occupation. Linear regression models were used to test
      associations between gender, SES, and a broad range of psychosocial factors.
      RESULTS: Women reported lower scale scores on decision latitude, coping, and self
      esteem, as well as more job strain, depression, and vital exhaustion, while men
      reported more cynicism (all p<0.05). Observed gender differences were still
      significant after control for effect of education, while after control for
      occupational status the effect of gender was lost for decision latitude and job
      strain. Significant interaction factors were found between gender and educational
      status for psychological demands, decision latitude, social integration, coping,
      and hopelessness. CONCLUSIONS: Gender differences, found for a broad range of
      psychosocial factors, could not be explained by SES. However, associations
      between gender and psychosocial factors were more salient at lower levels of SES.
      Psychosocial factors, especially decision latitude and social integration, may
      help explain why women with low SES experience poorer health.

PMID- 16449046
TI  - Social capital and lack of belief in the possibility to influence one's own
      health: a population-based study.
AB  - OBJECTIVES: To study the impact of social capital (social participation and
      trust) on lack of belief in possibility to influence health. METHODS: The Scania
      2000 public-health survey is a cross-sectional, postal questionnaire study
      including 13,604 persons aged 18-80 years which was conducted in 2000 by the
      regional healthcare authorities in Region Skane, southern Sweden, to investigate
      health-related risk factors in the population. A logistic regression model was
      used to investigate the association between social capital and lack of belief in
      possibility to influence health. The multivariate analyses analysed the
      importance of confounders on the differences in lack of belief in possibility to
      influence health according to the social capital variables. RESULTS: In total,
      31.0% of all men and 33.5% of all women lack belief in the possibility to
      influence their own health. Lack of belief in possibility to influence health was
      positively associated with both low social participation and low trust, although
      stronger for social participation than for trust. CONCLUSIONS: Low levels of
      social capital, particularly low social participation, is positively associated
      with lack of belief in the possibility to influence one's own health.

PMID- 16449047
TI  - On the importance of internalized consumption norms for ill health.
AB  - AIM: Relative deprivation has in previous studies been put forward as a possible
      mechanism in the income and health relation. To capture the importance of social
      comparisons analytically has been problematic due to the difficulty in
      identifying reference groups of significance for the individual. The authors
      suggest that using the individual's own preferences, arguing these to be
      preferences of both society and reference groups internalized by the individual,
      may partly bridge this problem. METHODS: The study is based on the Swedish Survey
      of Living Conditions 1998 including a list of 37 consumption items and
      activities. By counting the items that the individual cannot afford, but at the
      same time considers to be a necessity and something that all adults should
      afford, a measure of self-rated deprivation (SRD) is constructed. The outcome
      measure used is less than good self-rated health and limiting longstanding
      illness. Men and women aged 25-64 years are included. RESULTS: Over the different
      groups of self-rated deprivation a clear gradient in ill health, for both health
      measures, was found among women. The results for men seemed to dichotomize
      between non-deprived and those deprived on at least one item. The logistic
      regression models showed that even after adjusting for socioeconomic group and
      cash margin, there was a significant effect of self-rated deprivation.
      CONCLUSIONS: A significant relation was found between self-rated deprivation and
      ill health, both less than good health and limiting longstanding illness. Self
      rated deprivation had a stronger impact on women than men.

PMID- 16449048
TI  - Cost-effectiveness analysis of an alternative tuberculosis management strategy
      for permanent farm dwellers in South Africa amidst health service contraction.
AB  - AIM: To establish the cost-effectiveness of lay health workers (LHWs) in
      conjunction with the current, local tuberculosis (TB) control programme, amidst
      health service contraction. METHOD: A cost-effectiveness analysis, comparing
      direct time costs of the current TB management strategy among permanent farm
      dwellers, with an intervention, whereby LHWs are involved in TB control
      activities on farms. Measure of effectiveness was case finding and cure rates of
      adult new smear-positive (NSP) TB cases, alongside a randomized control trial
      (RCT): RESULTS: The observed cost reduction to the Boland Health District was 74%
      per case detected and cured on the intervention farms relative to the control
      farms. Intervention farms reached 83% successful treatment completion rate,
      control farms 65%. Although the successful treatment adherence was significantly
      different (18% letter). The improved case detection and cure rates were not
      statistically significant (chi-squared test). Direct LHW costs are borne by
      farmers. Farmers were motivated to bear costs by reduced job absenteeism and
      other positive side-effects. Even without outcome improvements costs per case
      cured were 59% lower on the intervention farms. CONCLUSION: TB control has
      suffered from budget reductions in South Africa. It is critically important to
      develop cost-effective strategies to reduce the TB burden. Costs to public
      budgets can be substantially reduced while maintaining or improving case
      detection and treatment outcomes, by using farm-based LHWs.

PMID- 16449049
TI  - HIV/AIDS knowledge and condom use among Somali and Sudanese immigrants in
      Denmark.
AB  - AIMS: This study explores the knowledge, attitudes and practices among Somali and
      Sudanese immigrants in Denmark with regard to HIV/AIDS and condom use. MATERIAL
      AND METHODS: A 78-item questionnaire, divided into five thematic sections, was
      given to 192 purposively selected Sudanese and Somalis of both sexes, aged 18-49,
      who had lived in Denmark for one or more years. It was administered in Arabic and
      Somali in four locations and supplemented by 13 semi-structured interviews.
      RESULTS: Education, sex, and nationality, but not length of residence in Denmark,
      were positively associated with knowledge about HIV/AIDS. Less than half of both
      men and women scored more than 70% on the knowledge portion of the questionnaire,
      while Sudanese knew more than Somalis. Men had a more negative attitude towards
      condoms than women, but greater knowledge about them. One-third of the women
      reported never having seen or heard of a condom, and almost half had never
      received information about condoms. Both sexes preferred receiving such
      information from the TV or friends instead of family doctors or HIV-positive
      individuals. CONCLUSIONS: This study suggests that knowledge about HIV/AIDS is
      low in these two Danish immigrant groups, both of which are characterized by
      reported incidence rates that are higher than the national average. The groups
      receive little information, while condom knowledge is particularly low among
      poorly educated women, and men have a negative attitude to condom use. The
      findings indicate a need for targeted, culturally sensitive HIV/AIDS information
      and advice.

PMID- 16449050
TI  - Road traffic injuries in India: a review of the literature.
AB  - AIMS: India is the largest country in the South Asian region with all the
      problems faced by rapidly developing nations, especially increasing motorization.
      In spite of such developments, there are limited data in the literature
      addressing the problem of road traffic injuries. This article is an attempt to
      estimate the magnitude of the problem through published literature. METHODS: This
      article is a systematic review of the literature on road traffic injuries in
      India, conducted using three electronic databases and hand-searching of the
      selected articles. Final analyses were conducted with 22 studies. RESULTS: Road
      traffic injuries are a significant burden on the health care system in India. The
      most commonly affected group is young males. Pedestrians constitute a large
      majority of the victims and there is high early mortality in most cases.
      CONCLUSIONS: There is lack of population-based data on road traffic injuries in
      India and there is large heterogeneity in the published data. This is an
      important research agenda for the country. Immediate steps are required to curb
      this problem to limit the loss of life and resources.

PMID- 16449051
TI  - Semicarbazide in Canadian bakery products.
AB  - Levels of semicarbazide were determined by liquid chromatography-tandem mass
      spectrometry using isotope dilution ((13)C(15)N(2)-semicarbazide) methodology,
      and they were measured, after hydrolysis in 0.125 M hydrochloric acid and
      derivatization with 2-nitrobenzaldehyde, as a sum of free and bound
      semicarbazide. Levels of semicarbazide in 11 bakery products, which were sampled
      at three time intervals from the same source, varied from not detected (<1ng g(
      1)) to 560 ng g(-1). In some instances, concentrations of semicarbazide varied
      between batches of the same product, at times more than tenfold, suggesting that
      the addition of azodicarbonamide to the same product is not standardized in many
      baking establishments.

PMID- 16449052
TI  - The simultaneous separation and determination of chloropropanols in soy sauce and
      other flavoring with gas chromatography-mass spectrometry in negative chemical
      and electron impact ionization modes.
AB  - Both gas chromatography-mass spectrometry in electron ionization (GC-MS-EI) and
      negative chemical ionization (GC-MS-NCI) modes are reported in this paper for the
      simultaneous determination of 1,3-dichloropropan-2-ol (1,3-DCP), 2,3
      dichloropropan-1-ol (2,3-DCP), 3-chloropropane-1,2-diol (3-MCPD) and 2
      chloropropane-1,3-diol (2-MCPD) in soy sauce and other flavoring. D(5)-3-MCPD
      (for 3-MCPD and 2-MCPD) and d(5)-1,3-DCP (for 1,3-DCP and 2,3-DCP) were used as
      the deuterium isotopic labelled internal standards. The feasibility of using
      heptafluorobutyric anhydride modified with triethylamine (HFBA-Et(3)N) as a new
      derivatization reagent to replace heptafluorobutyrylimidazole (HFBI) is proposed.
      Liquid/liquid extraction with hexane was introduced for high lipid content
      samples. A small survey was carried out of soy sauces (103 samples) and instant
      noodles (45 samples) and the applicability of GC-MS-NCI and GC-MS-EI was assessed
      in these different matrices.

PMID- 16449053
TI  - Evaluation of the Premi Test and comparison with the One-Plate Test for the
      detection of antimicrobials in kidney.
AB  - The Premi Test, a test kit designed for the rapid screening of antimicrobial
      residues in meat, fish and eggs, was evaluated and compared with the (modified)
      One-Plate Test, an agar diffusion assay. The performance characteristics
      described for qualitative, screening methods in Commission Decision 2002/657/EC
      were used for the evaluation. The Premi Test was found to detect a range of
      antimicrobials to MRL levels in kidney fluid but to have poorer sensitivity for
      some antimicrobials such as tetracyclines, sulphonamides, flumequine and
      streptomycin. The test was found not to be sensitive for the banned antimicrobial
      chloramphenicol. The One-Plate Test was found to detect most tetracyclines and
      flumequine to MRL levels but to be less sensitive than the Premi Test for most of
      the other classes of antimicrobials. Neither test alone provides a comprehensive
      screening test for antimicrobial residues in kidney at MRL levels. However, the
      Premi Test is fast, easy to use and rugged and, in combination with other
      antimicrobial tests, may be used to provide a comprehensive screening system for
      antimicrobials in tissues.

PMID- 16449054
TI  - Neoformation of boldenone and related steroids in faeces of veal calves.
AB  - Conflicting findings regarding the boldenone content of bovine faeces suggest it
      may be synthesized de novo in emitted faeces. We tested this hypothesis by
      analysing uncontaminated urine, fresh and various forms of dried faeces from 10
      calves (not given boldenone) by liquid chromatography/tandem mass spectrometry
      for 17alpha- and 17beta-boldenone (alpha and beta BOL); 1,4-androstadiene-3,17
      dione (ADD); 4-androstene-3,17-dione (AED), testosterone (T) and epitestosterone
      (ET). Urine contained no alpha BOL, beta BOL or ADD. The analysed substances were
      variably present in the rectal faeces, and at generally higher levels in faeces
      scraped from skin or stall floor. In pooled rectal faeces naturally dried for 13
      days, alpha BOL, ADD, AED and ET levels were extremely high (much higher than
      accounted for by increases due to drying), and beta BOL and T were absent. It is
      concluded that de novo synthesis of alpha BOL and metabolites occurs naturally in
      bovine faeces and only uncontaminated urine should be analysed for illegal
      boldenone.

PMID- 16449055
TI  - Lead content of dietary calcium supplements available in Brazil.
AB  - The lead and calcium content of calcium supplements available in Brazil were
      determined by graphite furnace and flame atomic absorption spectrometry,
      respectively. Samples were microwave-digested in concentrated HNO(3). Citric acid
      was used as a chemical modifier in the lead analysis. Supplements were classified
      into six categories: oyster industrialized (OI, n=4), oyster prepared in pharmacy
      (OP, n=3), refined industrialized (RI, n=6), refined prepared in pharmacy (RP,
      n=3), bone meal (B, n=3), and dolomite (D, n=4). Lead levels (microg g(-1) of
      measured calcium) were higher in D products (2.33), followed by OI, RP, OP, and
      RI products (1.46, 1.32, 1.29, 0.75), while B products had levels lower than the
      limit of quantification (0.02 microg g(-1) unit weight). Daily lead intake of
      eight supplements exceeded the limit of California, USA (1.5 microg g(-1)
      calcium), but none exceeded the federal limit of USA (7.5 microg g(-1) calcium)
      or the provisional tolerable lead intake by FAO/WHO (25 microg kg(-1) per week).

PMID- 16449056
TI  - Multi-element survey of wild edible fungi and blackberries in the UK.
AB  - A survey of 12 metals including lead (Pb), copper (Cu), cadmium (Cd), mercury
      (Hg), arsenic (As) and platinum (Pt) was carried out using ICP-MS in 34 samples
      of wild fungi and 48 samples of wild blackberries collected from sites across the
      UK. On a fresh weight basis (mg/kg) levels of Pb were in the range 0.003-5.990,
      Cu 0.596-34.800, Cd<0.001-19.6, Hg<0.001-4.150, As 0.001-0.972 and Pt (microg/kg)
      0.006-0.200, with higher concentrations found in fungi than in blackberries. The
      results of the survey showed that the concentrations of the metals were
      consistent with previous studies, where available. Concentrations in wild fungi
      of Pt, tin (Sn), and titanium (Ti) were significantly higher at urban sites than
      at rural sites. Urban blackberries had significantly higher levels of Pb, Ti, and
      Cd than rural ones, but lower levels of manganese (Mn). Pb, Ti and Sn
      concentrations were significantly higher in blackberries sampled near main roads
      rather than in rural areas.

PMID- 16449058
TI  - Contamination of honey by chemicals applied to protect honeybee combs from wax
      moth (Galleria mellonela L.).
AB  - Greek honey was monitored during a three-year surveillance program for residues
      of chemicals used to protect honey-bee combs from wax-moth. A total of 115
      samples purchased from stores (commercial samples) and 1060 samples collected
      from beekeepers (bulk samples) were analysed for 1,4-dichlorobenzene (p-DCB), 1,2
      dibromoethane (DBE) and naphthalene. A purge & trap-gas chromatograph-mass
      spectrometer system was used for the analysis. During the first year of the
      study, 82.9% of the commercial samples had residues of p-DCB that exceeded the
      established limit of 10 microg kg(-1), whilst during the second year 53.6% and
      during the third 30% exceeded the limit. The percentage of beekeepers samples
      that had more than 10 microg kg(-1) decreased from 46.6 to 34.7% and 39.8%
      respectively during the three consecutive years of analysis. Only one commercial
      sample (0.8%) had residues of DBE that exceeded 10 microg kg(-1) during the three
      years study, while 9.9% of the beekeepers samples exceeded this limit in 2003.
      This percentage fell to 1.9 and 2.8% during the following years. Naphthalene was
      found in more commercial samples than in samples from beekeepers during the first
      year, but decreased to similar levels during the next two years. Honeys that are
      produced earlier in the season are more contaminated those produced later.

PMID- 16449057
TI  - Variability of organophosphorus insecticide residues in large size crops grown in
      commercial farms in Brazil.
AB  - Field trials were conducted in commercial agricultural areas in Brazil to
      determine the variability of residues of parathion methyl, diazinon and
      methidathion in individual units of large crops treated twice with a mixture of
      the three pesticides. Over 120 random samples were collected, extracted with
      ethyl acetate and residues determined by GC/FPD. The recoveries and their
      coefficient of variation were, in general, within the acceptable levels during
      sample analyses. Residues in papaya and mango were not affected by the position
      of the fruits in the plant, apparently more or less exposed to the pesticides.
      Variability factor ?, defined as the 97.5th percentile divided by the mean of
      residues in all samples taken from a field ranged from 2.0-2.6. The variability
      of residues within the plant contributed to about 34-61% of the field
      variability. The results found in this study support the variability factor of 3
      adopted by the FAO/WHO for the deterministic estimation of dietary acute intake
      of pesticides.

PMID- 16449059
TI  - Monitoring of pesticide residues in apples, lettuce and potato of the Slovene
      origin, 2001-04.
AB  - Apples, lettuce and potatoes (404 samples) produced in the Republic of Slovenia
      were analysed for pesticide residues at the Agricultural Institute of Slovenia,
      Ljubljana, in 2001-04. Sampling from eight agricultural production areas was
      performed at market producers at the harvesting of products or in storehouses
      after the pre-harvest interval of plant protection products used. Samples
      exceeding the maximum residue levels were the following: three apple samples
      (2.0%) containing 0.33-2.24 mg kg(-1) (phosalone and tolylfluanid), three lettuce
      samples (3.1%) containing 0.14-6.36 mg kg(-1) (dimethoate, dithiocarbamates and
      metalaxyl) and 36 potato samples (23.1%) containing 0.06-0.51 mg kg(-1)
      (dithiocarbamates). Residues of two or more active substances were found in 73
      apple samples (48.3%), of which the maximum residue limit (MRL) was exceeded by
      three samples (2.0%) with the values ranging from 0.33 to 2.24 mg kg(-1), and
      nine lettuce samples (9.3%), for which the MRL was exceeded by three samples
      (3.1%) with values from 0.14 to 6.36 mg kg(-1). In potato samples, only residues
      of dithiocarbamates or no residues at all were found. Residues of the
      dithiocarbamate group were the most frequently found, i.e. in 66 apple samples
      (43.7%), 30 lettuce samples (30.9%) and 38 potato samples (24.4%).

PMID- 16449060
TI  - Aflatoxins in ginseng roots.
AB  - Ginseng roots can be infected by molds during growth, harvest and storage and
      result in contamination with mycotoxins. In this study, an analytical method for
      the determination of aflatoxins B(1), B(2), G(1) and G(2), a group of
      structurally similar mycotoxins, in ginseng root was developed. Test samples were
      extracted with methanol-water (8?+?2), diluted and passed through an
      immunoaffinity column packed with antibodies specific for aflatoxins. The
      purified extract was then derivatized with a mixture of water, trifluoroacetic
      acid and acetic acid. Aflatoxins were then separated and quantified by reverse
      phase liquid chromatography (LC) with fluorescence detection. Recoveries of total
      aflatoxins at 2, 4, 8 and 16 ng/g added to toxin-free 4 to 5-year old dried
      sliced Wisconsin ginseng were 92, 77, 91 and 83% respectively; and relative
      standard deviations were 3.6, 8.0, 6.9 and 2.0% respectively. A total of 11 wild
      simulated and 12 cultivated ginseng root samples were analysed for aflatoxins.
      All cultivated roots were found to be free of aflatoxin contamination. Two of the
      wild simulated roots contained total aflatoxins B(1), B(2), G(1) and G(2) at 15.1
      and 15.2 ng/g. One moldy ginseng root purchased from a grocery store was found to
      be contaminated with aflatoxins at 16 ng/g.

PMID- 16449061
TI  - Ochratoxin A and citrinin loads in stored wheat grains: impact of grain dust and
      possible prediction using ergosterol measurement.
AB  - Crop storage should be carried out under hygienic conditions to ensure safe
      products, but sometimes grain dust which has settled from previous storage may be
      left over and incorporated to the following stored grains. This paper describes
      the results obtained using a lab model developed in order to assess the impact of
      grain dust incorporation for its direct contribution as a contaminant but also as
      an inoculum in stored wheat. Settled grain dust (4 samples) released from Belgian
      grain storages were collected and analysed by HPLC for ergosterol, ochratoxin A
      (OTA) and citrinin (CIT) content. For OTA and for ergosterol, there was a high
      degree of variability in concentrations found in the dust samples (from 17.3-318
      ng g(-1) and from 39-823 microg g(-1), respectively) whilst for CIT, the range
      was less significant (from 137-344 ng g(-1)). Incorporation of grain dust into
      wheat storage contributed to an increase in the concentrations of mycotoxins in
      the stored grain. Dust acts as a contaminant and as an inoculum. According to
      these two ways, patterns of mycotoxin generation vary with the nature of the
      mycotoxin, the mycotoxigenic potential of dust and the water activity of the
      wheat. OTA and CIT showed a very versatile image when considering the amounts of
      toxins produced under the selected experimental conditions. The development of a
      robust tool to forecast the mycotoxigenicity of dust was based on the
      determination of ergosterol content as a general marker of fungal biomass.
      Present results suggest that this predictive tool would only be valid for
      predicting the contamination level of CIT and OTA at reasonable moisture content
      (14-20%). The potential risk of having highly contaminated batches from stock to
      stock may thus occur and this paper discusses possible pathways leading to OTA
      and CIT contamination either under wet or dry storage conditions. We therefore,
      recommend taking precautionary measures not only by controlling and maintaining
      moisture at a reasonable level during storage of the raw materials but also by
      paying more attention to the cleaning of the stores before loading in the new
      harvests.

PMID- 16449062
TI  - Distribution and stability of Aflatoxin M1 during processing and ripening of
      traditional white pickled cheese.
AB  - The distribution of aflatoxin M(1) (AFM(1)) has been studied between curd, whey,
      cheese and pickle samples of Turkish white pickled cheese produced according to
      traditional techniques and its stability studied during the ripening period.
      Cheeses were produced in three cheese-making trials using raw milk that was
      artificially contaminated with AFM(1) at the levels of 50, 250 and 750 ng/l and
      allowed to ripen for three months. AFM(1) determinations were carried out at
      intervals by LC with fluorescence detection after immunoaffinity column clean-up.
      During the syneresis of the cheese a proportionately high concentration of AFM(1)
      remained in curd and for each trial the level was 3.6, 3.8 and 4.0 times higher
      than levels in milk. At the end of the ripening, the distribution of AFM(1) for
      cheese/whey + brine samples was 0.9, 1.0 and 1.3 for first, second and third
      spiking respectively indicating that nearly half of the AFM(1) remained in
      cheese. It has been found that only 2-4% of the initial spiking of AFM(1)
      transferred into the brine solution. During the ripening period AFM(1) levels
      remained constant suggesting that AFM(1) was quite stable during manufacturing
      and ripening.

PMID- 16449063
TI  - Aflatoxin M1 and cyclopiazonic acid in fluid milk traded in Sao Paulo, Brazil.
AB  - Aflatoxin M(1) (AFM(1)) and cyclopiazonic acid (CPA) were determined in 48
      samples of grade A-C and ultra-high-temperature (UHT)-treated fluid commercial
      milk from Sao Paulo, Brazil, from July to December 2004. AFM(1) and CPA
      determinations were carried out by HPLC. Results showed 37 (77.1%) positive
      samples for AFM(1) at levels of 0.011-0.251 microg l(-1) milk, which were below
      the tolerance limit for AFM(1) in milk as adopted by Brazilian regulations. Mean
      levels of AFM(1) in grades A-C and UHT milk were 0.060+/-0.080, 0.056+/-0.063,
      0.064+/-0.041 and 0.075+/-0.048microg l(-1), respectively. CPA was detected in
      two samples (4.2%) of grade A milk at levels of 6.4 and 9.7 microg l(-1). This is
      the first report of the occurrence of CPA in milk in Brazil. It was concluded
      that the incidence of AFM(1) in milk traded in Sao Paulo is low, but the
      simultaneous occurrence of CPA, even at low levels, warrants concern about AFM(1)
      in milk and milk products.

PMID- 16449064
TI  - Typical diffusion behaviour in packaging polymers - application to functional
      barriers.
AB  - When plastics are collected for recycling, possibly contaminated articles might
      be recycled into food packaging, and thus the contaminants might subsequently
      migrate into the food. Multilayer functional barriers may be used to delay and to
      reduce such migration. The contribution of the work reported here is to establish
      reference values (at 40 degrees C) of diffusion coefficients and of activation
      energies to predict the functional barrier efficiency of a broad range of
      polymers (polyolefins, polystyrene, polyamide, PVC, PET, PVDC, [ethylene vinyl
      alcohol copolymer], polyacrylonitrile and [ethylene vinyl acetate copolymer]).
      Diffusion coefficients (D) and activation energies (Ea) were measured and were
      compiled together with literature data. This allowed identification of new trends
      for the log D=f(molecular weight) relationships. The slopes were a function of
      the barrier efficiency of the polymer and temperature. The apparent activation
      energy of diffusion displayed two domains of variation with molecular weight (M).
      For low M (gases), there was little variation of Ea. Focusing on larger
      molecules, high barrier polymers displayed a larger dependence of Ea with M. The
      apparent activation energy decreased with T. These results suggest a
      discontinuity between rubbery and glassy polymers.

PMID- 16449065
TI  - Migration of formaldehyde and acetaldehyde into mineral water in polyethylene
      terephthalate (PET) bottles.
AB  - The levels of formaldehyde (FA) and acetaldehyde (AA) in polyethylene
      terephthalate (PET) bottles and in commercial mineral water are reported. All the
      water samples bottled in Japan contained detectable levels of FA (10.1-27.9
      microg l(-1)) and AA (44.3-107.8 microg l(-1)). Of 11 European bottled water
      samples, eight did not contain either FA or AA, while the remaining three had
      detectable levels of FA (7.4-13.7 microg l(-1)) and AA (35.9-46.9 microg l(-1)).
      In three North American bottled water samples, two contained FA (13.6 and 19.5
      microg l(-1)) and AA (41.4 and 44.8 microg l(-1)), and one did not. Regardless of
      the region of origin, all the sterilized water samples contained FA and AA,
      whilst in contrast, none of the unsterilized water without carbonate contained FA
      or AA. Of the carbonated water samples, three contained FA and AA, and one did
      not. When fortified with FA and AA, the commercial water sample without otherwise
      detectable FA and AA was able to reduce levels, although the commercial water
      sample containing FA and AA could not. The presence of bacteria in the commercial
      water samples was investigated using an ATP-based bioluminescent assay and
      heterotrophic plate count method. The commercial water without FA and AA
      contained heterotrophic bacteria, whilst the commercial water with FA and AA did
      not contain detectable bacteria. It is suggested that in this case both FA and AA
      migrated from PET materials, but were subsequently decomposed by the
      heterotrophic bacteria in the unsterilized water.

PMID- 16449067
TI  - Planning, problem-solving and organizational abilities in children following
      traumatic brain injury: intervention techniques.
AB  - Due to the mechanisms involved in traumatic brain injury (TBI), the frontal lobes
      are often impacted. As the frontal regions of the brain are believed to subsume
      executive functioning, then it follows that post-TBI deficits may be seen in this
      domain. Executive functioning broadly refers to a set of inter-related skills
      necessary to maintain an appropriate problem-solving set for the attainment of a
      future goal and may include areas such as attentional control, planning, problem
      solving, cognitive flexibility, abstraction and information processing. The
      literature available on interventions for executive difficulties following TBI is
      minimal, with that focused on the paediatric population even more limited. From
      the few evaluation studies available, results tend to suggest that specific types
      of intervention lead to positive outcomes. However, as the interventions are few
      and often based on case studies, there is much need for more evaluation studies
      to be conducted.

PMID- 16449068
TI  - A role for sleep in brain plasticity.
AB  - The idea that sleep might be involved in brain plasticity has been investigated
      for many years through a large number of animal and human studies, but evidence
      remains fragmentary. Large amounts of sleep in early life suggest that sleep may
      play a role in brain maturation. In particular, the influence of sleep in
      developing the visual system has been highlighted. The current data suggest that
      both Rapid Eye Movement (REM) and non-REM sleep states would be important for
      brain development. Such findings stress the need for optimal paediatric sleep
      management. In the adult brain, the role of sleep in learning and memory is
      emphasized by studies at behavioural, systems, cellular and molecular levels.
      First, sleep amounts are reported to increase following a learning task and sleep
      deprivation impairs task acquisition and consolidation. At the systems level,
      neurophysiological studies suggest possible mechanisms for the consolidation of
      memory traces. These imply both thalamocortical and hippocampo-neocortical
      networks. Similarly, neuroimaging techniques demonstrated the experience
      dependent changes in cerebral activity during sleep. Finally, recent works show
      the modulation during sleep of cerebral protein synthesis and expression of genes
      involved in neuronal plasticity.

PMID- 16449069
TI  - Rehabilitation care in paediatrics in the Czech Republic.
AB  - The aim of this work is to inform about the present situation in the care of
      disabled children in the Czech Republic. It contains the evaluation of the
      present situation and displays plans of care in the future.

PMID- 16449070
TI  - Wheeling efficiency: the effects of varying tyre pressure with children and
      adolescents.
AB  - PURPOSE: Clinicians often observe child wheelchair users wheeling on tyres that
      are not inflated to manufacturer's recommendations. The purpose of this study was
      to investigate changes in energy expenditure that are related to decreased tyre
      pressure. METHODS: A within subject repeated measures design was used to assess
      the energy requirements of wheeling with four randomized tire inflation levels
      (25, 50, 75 and 100% of recommended tire pressure, 100 psi). All 10 subjects
      (mean age 14.2 +/- 2.3 years completed four 5-minute trials (one for each tyre
      pressure), while wheeling at a constant, self-selected velocity. Heart rate and
      wheeling velocity were measured. RESULTS: There was no change in wheeling
      velocity with changes in tyre pressure; however, energy expenditure was found to
      increase by over 15% with decreasing tyre pressure (p < 0.05). CONCLUSIONS: In
      order for children to minimize their energy expenditure and, thus, improve their
      independence, clinicians and parents must be educated as to the importance of
      regular wheelchair tyre inflation regimes.

PMID- 16449071
TI  - Discrete bimanual co-ordination in children and young adolescents with
      hemiparetic cerebral palsy: recent findings, implications and future research
      directions.
AB  - Bimanual co-ordination is a field that has generated much research interest. It
      is clear that when hands move simultaneously there is a tendency for such
      movements to be synchronized. This phenomenon has also been observed in
      individuals with congenital brain damage, such as cerebral palsy. This paper
      provides an overview of past and current work in the area of bimanual co
      ordination looking at the nature of the coupling and the underlying control of
      such movements. Work on 'non-disabled' individuals and unimanual reaching and
      grasping is included, but the main emphasis is bimanual co-ordination in children
      with hemiparetic cerebral palsy. The direction for future research is discussed
      and consideration given to the therapeutic implications of such work.

PMID- 16449072
TI  - Micro-switch programmes for students with multiple disabilities and minimal motor
      behaviour: assessing response acquisition and choice.
AB  - This study assessed (a) whether three girls with multiple disabilities and
      minimal motor behaviour could acquire pairs of responses taught through micro
      switch-based programmes and (b) how the girls would eventually choose between
      those responses. In relation to the choice issue, a response-choice analysis was
      conducted to find out whether possible differences in performance rates for the
      two responses were due to the stimuli linked to them and/or to potential response
      preferences. Results indicated that all three girls succeeded in the acquisition
      of the two responses programmed for them and showed clear response choices. The
      choices seemed to be largely motivated by the stimuli linked to the responses.
      Implications of these findings were discussed, including the need to assess their
      generality and extend the scope of the work in this area.

PMID- 16449074
TI  - A comparison of goal attainment scaling and the Canadian Occupational Performance
      Measure for paediatric rehabilitation research.
AB  - PURPOSE: To investigate the relative utility of Canadian Occupational Performance
      Measure (COPM) (adapted for children) and Goal Attainment Scaling (GAS) as
      outcome measures for paediatric rehabilitation. METHODS: A two-group pre-post
      design investigated the impact of a 3-month programme. Forty-one children with
      spastic hemiplegic cerebral palsy (mean 3.9 years; GMPM level 1; 21 boys, 10
      girls) were randomized to occupational therapy only and occupational therapy plus
      one Botulinum Toxin A injection. The latter was considered a 'proven'
      intervention for the purpose of this instrumentation study. Intervention impact
      was investigated using GAS and COPM. Instrument sensitivity, convergent validity,
      goal/problem profiles and administration were evaluated. RESULTS: Both
      instruments were sensitive to within group change and detected significant
      between group change. Likert scale coding for GAS scores was more sensitive than
      the traditional weighted GAS or COPM. Different constructs were measured by each
      instrument. COPM was more time efficient in training, development and
      administration. CONCLUSION: Study aim, logistic and resource factors should guide
      the choice of COPM and/or GAS instruments as both are sensitive to change with a
      proven intervention and both evaluate different constructs.

PMID- 16449073
TI  - Growth in pre-pubertal children with myelomeningocele (MMC) on growth hormone
      (GH): the KIGS experience.
AB  - PURPOSE: To analyse the auxological data of children with myelomeningocele (MMC)
      on growth hormone (GH) therapy whose growth data was documented within KIGS
      (Pfizer International Growth Database). Longitudinal growth data of a sub-group
      of pre-pubertal children were studied after a treatment period of 3 years.
      PATIENTS AND METHODS: Eighty patients (38 m, 42 f) with MMC with a median
      chronological age (CA) of 11.6 years (at latest visit) on GH were registered in
      the KIGS database. In 52 patients, GH deficiency was documented. GH therapy
      started with a median dose of 0.23 mg kg(-1) per week. The 3-year longitudinal
      growth was analysed in 21 patients (13 m, 8 f; median CA 9.2 years, latest
      visit), all of whom were pre-pubertal at start and during GH therapy. RESULTS: GH
      therapy started at 7.5 years with a dose of 0.23 mg kg(-1) per week. Birth length
      SDS (-0.51) and mid-parental height SDS (+0.07) were in the normal range. BMI SDS
      at start was +0.24, at latest visit -0.03. After a median treatment duration of
      3.0 years (latest visit), height SDS improved from -2.97 (start of GH) to -2.01.
      The sub-group of pre-pubertal MMC patients started GH therapy (dose 0.22 mg kg(
      1) per week) at 6.2 years. Growth velocity (GV) SDS increased significantly (at
      start: -1.77; 1 year: +2.60, 2 years: +2.25, 3 years: +1.24), thus height SDS
      improved from -3.25 at start to -1.87 at 36 months. BMI SDS was in the normal
      range and remained unchanged during GH therapy. No major side effects of GH were
      recorded. CONCLUSION: GH had positive effects on height SDS in MMC patients. The
      analysis of the longitudinal growth data of pre-pubertal MMC patients showed a
      significant increase in GV SDS and improvement of height SDS.

PMID- 16449075
TI  - Physical activity patterns in children with and without Down syndrome.
AB  - PURPOSE: To describe physical activity (PA) patterns in children with Down
      syndrome (DS) compared to their unaffected siblings. METHODS: Children with DS (n
      = 28) and their siblings (n = 30), between 3-10-years (mean +/- SD 7.1 +/- 2.1
      years) participated in a nutrition and growth study. PA was measured over 7 days
      using accelerometers. RESULTS: Children with DS were younger (6.6 vs. 7.1 years)
      and heavier (BMI 18.4 vs. 16.7 kg m(-2)) than their siblings (p < 0.05). Overall,
      participants accumulated 2.5 hours per day in moderate- (MPA) and 59 min per day
      in vigorous-intensity activity (VPA), consistent with the current PA
      recommendations for children. Children with DS accumulated less VPA than their
      siblings (49.5 vs. 68.6 minutes per day; p = 0.04) and for shorter bouts (2.5 vs.
      5.1 minutes per bout; p < 0.01), but spent similar time in MPA and low-intensity
      PA. Analyses adjusted for age, sex, race, ethnicity, income, maternal education
      and BMI showed similar results. CONCLUSIONS: Children with DS participated in
      less total and sustained VPA and had higher BMI levels compared with their
      siblings. Because children with DS have a tendency toward childhood obesity,
      increasing participation in VPA may be appropriate for prevention of obesity and
      promotion of lifelong health.

PMID- 16449076
TI  - Botulinum toxin type-A and plaster cast treatment in children with upper brachial
      plexus palsy.
AB  - BACKGROUND AND PURPOSE: Electrical stimulation, physical therapy and occupational
      therapy remain the main treatment for children with upper brachial plexus palsy
      (UBPP), when surgery has been excluded. A pilot study was undertaken to
      investigate whether botulinum toxin type A (BoNT-A) and plaster casting, as
      adjunct to the physical therapy, decreased muscle contracture and improved the
      position and function of the impaired arm. METHOD: Twenty-two children (mean age
      5.6 +/- 3.4 years) with mild UBPP who previously underwent serial cast treatment,
      unsuccessfully, were enrolled. Neurological impairment and functional status were
      quantified using Medical Research Council (MRC) and Mallet scales and the Nine
      Hole Peg Test (NHPT). Elbow extension was measured using a goniometer. Biceps
      brachii, brachialis, pronator teres and pectoralis major muscles were injected
      with 22 units kg(-1) BoNT-A (Dysport, Ipsen). After injection, the treated arm
      was fixed with a plaster cast and progressively lengthened over 14 days. The cast
      was maintained for 30 days. Assessments of elbow extension, MRC, Mallet Scale and
      NHPT were made at baseline, 3, 6 and 12 months. RESULTS: After BoNT-A injection,
      children had significant improvement of active elbow extension (15.5 degrees +/-
      17.1 at 12 months after injection, compared with 42.0 degrees +/- 10.4 at
      baseline; p < 0.001). NPHT scores improved significantly over the 12 months (51.1
      +/- 21.8 seconds compared with 56.7 +/- 19.3 seconds at baseline, p < 0.01). MRC
      and Mallet scale scores of the paretic muscles were unchanged. CONCLUSION: The
      children showed a reduction in muscular contracture and improvements of the arm
      position and elbow extension. The data support the use of BoNT-A and plaster
      casting as an adjunct to physical therapy, in the treatment of children with mild
      UBPP.

PMID- 16449080
TI  - Repeated 0.5-Gy gamma-ray irradiation attenuates autoimmune manifestations in MRL
      lpr/lpr mice.
AB  - PURPOSE: MRL-lpr/lpr mice, a model for various autoimmune diseases, were
      repeatedly irradiated with 0.5 Gy of gamma-rays, and changes in their autoimmune
      manifestations were investigated. MATERIALS AND METHODS: MRL-lpr/lpr mice at 13
      weeks of age were maintained in plastic cages and exposed whole-body to 0.5 Gy
      gamma-ray irradiation from a 137Cs source 5 times per week for 4 weeks, from the
      time they were 13 weeks old until they reached 17 weeks old. Changes of
      autoimmune manifestations were examined 3 weeks later at the 20th week. RESULTS:
      Splenomegaly, lymphadenopathy, and proteinuria in MRL-lpr/lpr mice were clearly
      ameliorated by a total dose of 10 Gy (0.5 Gy/day x 5 days/week for 4 weeks).
      Histologically severe disease-specific damage to the kidney and the salivary
      gland, i.e., glomerulonephritis and sialoadenitis, was also improved after
      irradiation. CD3+ CD4- CD8- CD45R/B220+ T cell numbers, which proliferate
      abnormally in MRL-lpr/lpr mice, were significantly decreased by the irradiation,
      possibly through induction of apoptosis. The elevated NO2- and NO3- (NO(x-)
      production by macrophages of MRL-lpr/lpr mice was lowered by the irradiation. The
      irradiation also prolonged the life span of MRL-lpr/lpr mice. These phenomena may
      contribute to the amelioration of autoimmune manifestations in MRL-lpr/lpr mice
      exposed to repeated small-doses of gamma-rays. CONCLUSIONS: Repeated small-dose
      gamma-ray exposure ameliorates the autoimmune manifestations in MRL-lpr/lpr model
      mice.

PMID- 16449079
TI  - Activation of immunological network by chronic low-dose-rate irradiation in wild
      type mouse strains: analysis of immune cell populations and surface molecules.
AB  - PURPOSE: To analyse the effects of chronic whole body low-dose-rate irradiation
      on the immune system in various wild-type mouse strains in comparison with the
      effects from acute high-dose-rate irradiation. MATERIALS AND METHODS: Wild-type
      mouse strains (C57BL/6, BALB/c, C3H/He, DBA/1, DBA/2 and CBA) were observed after
      chronic low-dose-rate gamma irradiation at 1.2 mGy hour(-1) by intensive analysis
      of immune cell populations and their various surface molecules, together with
      antibody-producing activity both with and without immunization by sheep red blood
      cells (SRBC). The cell surface functional molecules [cluster of differentiation
      (CD) 3, CD4, CD8, CD19, CD45R/B220, intercellular adhesion molecule (ICAM)-1,
      Fas, natural killer (NK)-1.1, chemokine [C-X-C motif] receptor 4 (CXCR4) and
      chemokine [C-C motif] receptor 5 (CCR5)] and activation molecules [thymocyte
      activating molecule (THAM), CD28, CD40, CD44H, CD70, B7-1, B7-2, OX-40 antigen,
      cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD30 ligand and CD40
      ligand] were studied in the bone marrow, thymus, spleen, lymph nodes and
      peripheral blood by flow cytometry. RESULTS: By chronic low-dose-rate irradiation
      alone, CD4+ T cells and CD8 molecule expression increased significantly by a
      maximum of 30%, while CD40+ B cells decreased significantly. Increases of CD4+ T
      cells, CD40+ B cells and anti-SRBC antibody-producing cells by immunization were
      significantly enhanced by continuous low-dose-rate irradiation at 1.2 mGy hour(
      1). CD3- CD4+ T cells, representative of abnormal immune cells, were absent in
      the chronically low-dose-rate-irradiated mice, while a dose-dependent increase of
      these cells was found in acutely high-dose-rate-irradiated mice given the same
      total doses. CONCLUSION: Chronic low-dose-rate radiation activated the immune
      system of the whole body.

PMID- 16449081
TI  - The radiation sensitivity of human chromosomes 2, 8 and 14 in peripheral blood
      lymphocytes of seven donors.
AB  - PURPOSE: To investigate if deviations from DNA-proportional distribution of
      radiation-induced chromosomal aberrations are individually variable. MATERIALS
      AND METHODS: Peripheral blood lymphocytes were collected from seven healthy
      donors and exposed to different doses of gamma rays. Chromosomes 2, 8 and 14 were
      painted in different colors and aberrations scored with the help of an image
      analysis system. RESULTS: Chromosome 2 was generally less sensitive than expected
      on the basis of DNA-proportional distribution and the extent of inter-donor
      variability was minimal. A higher than expected frequency of aberrations was
      found in chromosome 14 of five donors, while a higher than expected frequency of
      aberrations was found in chromosome 8 of two donors. CONCLUSIONS: Inter-donor
      variability may explain some of the controversies regarding the inter-chromosomal
      distribution of radiation-induced aberrations.

PMID- 16449082
TI  - Low-dose hyperradiosensitivity of human glioblastoma cell lines in vitro does not
      translate into improved outcome of ultrafractionated radiotherapy in vivo.
AB  - PURPOSE: Low dose hyperradiosensitivity (HRS) has been observed in HGL21- and
      T98G human glioblastoma cells in vitro. The present study investigates whether
      these effects translate into improved outcome of ultrafractionated irradiation
      (UF) in vivo. MATERIAL AND METHODS: T98G or HGL21 were transplanted on the hind
      leg of nude mice. Tumours were irradiated with UF (3 fractions of 0.4 Gy per day,
      interval 4 h, 7 days per week) or with conventional fractionation (CF; 1 fraction
      of 1.68 Gy per day, 5 days per week) over 2 or 4 weeks in HGL21 and 2,4 or 6
      weeks in T98G. In HGL21, graded top-up doses under clamped hypoxia were applied
      after 4 weeks of fractionated irradiation. Additional groups of animals were
      irradiated with single doses under clamp hypoxic conditions with or without whole
      body irradiation (WBI) before tumour transplantation. Experimental endpoints were
      growth delay (time to 5-fold starting volume, GD(V5)) and local tumour control.
      RESULTS: In T98G tumours median relative GD(V5) was 1.2 [95% C.I. 0.96; 8] in the
      CF and 0.8 [0.7; 1.02] in the UF arm (p = 0.009) indicating that
      ultrafractionation is less efficient than conventional fractionation. The TCD50
      value of 33.5 Gy [22; 45] after UF was higher than TCD50 of 23.6 Gy [16; 31]
      after CF (p = 0.15). In HGL21 the median relative GD(V5) was not significantly
      different between CF and UF. The top-up TCD50 value of 16.1 Gy [95% C.I. 9; 23
      Gy] after CF was significantly lower than the corresponding value of 33.2 Gy [23;
      44] after UF irradiation (p = 0.007), indicating a higher efficacy of CF compared
      to UF. CONCLUSION: The results on human T98G and HGL21 glioblastoma do not
      support the hypothesis that HRS in vitro translates into improved outcome of
      ultrafractionated irradiation in vivo.

PMID- 16449083
TI  - Radioprotectant combinations spare radiation-induced damage to the physis more
      than fractionation alone.
AB  - PURPOSE: The aim of this study was to determine if fractionation and individual
      or combinations of radioprotectants could minimize damage to physeal longitudinal
      growth in an animal model to any greater extent than fractionation alone.
      MATERIALS AND METHODS: Sixty-three weanling male Sprague-Dawley rats were
      randomized into seven equal groups. Five groups received a total 25 Gy radiation
      exposure in three equal fractions to the right knee with the left as non
      irradiated control. For each group, pentoxifylline, misoprostol, and amifostine
      were given individually and amifostine was also given in combination with each of
      the other drugs prior to the radiation fractions. One group each received 25 Gy
      in one or three fractions without radioprotection. At six weeks, limb lengths and
      histomorphometry were assessed. RESULTS: The single fraction of 25 Gy caused a
      mean tibial length discrepancy of 24.4%. Fractionation decreased this to 18.8% (p
      < 0.001). Beyond fractionation alone, the mean femoral length discrepancies were
      significantly decreased by each of the added individual and combination
      radioprotectant drugs (p < 0.0004). The smallest absolute femoral length
      discrepancy (11%) was achieved with fractionation and the combination of
      amifostine and misoprostol. CONCLUSIONS: Radioprotectants may be beneficial in
      growth plate radioprotection, alone or in combination.

PMID- 16449084
TI  - Infrared microspectroscopy study of gamma-irradiated and H2O2-treated human
      cells.
AB  - PURPOSE: Fourier transform infrared microspectroscopy (FT-IRM), which allows
      simultaneous detection of biochemical changes in the various cellular
      compartments, was used as a new analytical tool to study early radiation- and
      oxidation-induced cellular damage at the molecular level in single human cells.
      MATERIALS AND METHODS: HaCaT keratinocytes were given a single dose of 6 Gy
      (137Cs) or 650 microM H2O2, neither of which is cytotoxic (neutral red assay) but
      both of which result in less than 10% clonogenic survival, and deposited on zinc
      sulphur (ZnS) windows for infra-red (IR) spectra acquisition, immediately and 2 h
      after treatment. DNA damage was assessed by comet assays in alkaline conditions.
      RESULTS: Comet assays showed that the yield of DNA damage was higher after H2O2
      treatment than after gamma-irradiation. The comparison between spectra of
      irradiated and H2O2-treated cells showed common changes, but H2O2 treatment
      presented a broader spectrum of cellular oxidation than ionizing radiation. The
      bands characteristic of deoxyribose/ribose in nucleic acids centered at 966 and
      997 cm(-1), the bands characteristic of nucleic acid bases centered at 1572,
      1599, and 1691 cm(-1), as well as the bands characteristic of ordered secondary
      structure of DNA centered at 1713-1716 cm(-1), were changed in absorbance,
      sometimes accompanied by a shift. The bands characteristic of proteins centered
      at 1515, 1530, 1544 and 1640 cm(-1) were changed in absorbance indicating a
      decrease in secondary structure of proteins. Moreover, the absorbance of the
      bands at 1515 and 1630 cm(-1) was correlated the yield of reactive oxygen
      species. Two hours after both treatments most changes were persistent, suggesting
      either irreversible or not easily repaired damage or persistent oxidative stress.
      CONCLUSION: As we previously demonstrated in radiation-induced apoptosis studies,
      these results show that FT-IRM, in correlation with other cellular biology
      techniques, might be useful for assessing immediate radiation- and oxidative
      induced damage to nucleic acids and proteins in single human cells.

PMID- 16449085
TI  - Subchronic exposure of hsp70.1-deficient mice to radiofrequency radiation.
AB  - PURPOSE: Heat shock protein 70 (HSP70) is one of the most inducible proteins to
      play a cytoprotective role under stressful conditions. Previously we generated
      hsp70.1-deficient mice to elucidate the in vivo function of HSP70 in detail. The
      renal tissues and embryonic fibroblasts of these mice were shown to be more
      vulnerable to hyperosmotic stress. Since RF (radiofrequency) energy has been
      suggested to be an environmental stressor, we carried out a study to determine
      whether sub-chronic RF exposure can cause constitutive induction of a stress
      response at a cellular and/or molecular level in hsp70.1-deficient mice due to
      repeated stimulation. MATERIALS AND METHODS: Eight-week-old hsp70.1-deficient
      mice were exposed twice daily for 45 min, with a 15 min interval, 5 days a week
      for 10 weeks. Whole-body average specific absorption rate was 0.4 W/Kg for fields
      of both 849 MHz and 1763 MHz. Major tissues were histopathologically analysed,
      and immunocytochemically evaluated for cell proliferative activity. Apoptosis was
      investigated by TdT-mediated dUTP nick-end labeling (TUNEL) assay. To determine
      whether RF radiation elicits a stress response, the expression level of heat
      shock proteins (HSP) and phosphorylation of the stress-activated kinases were
      also observed by western blots. RESULTS: No difference was observed in the
      histopathological analysis between sham- and RF-exposed mice. There was no
      evidence of increased proliferative and apoptotic activities. The levels of
      HSP90, HSP70, and HSP25 showed no obvious changes. RF exposure did not affect the
      phosphorylation status of the major stress-activated kinase (MAPK); extracellular
      signal-regulated kinase 1/2 (ERK1/2), C-Jun N-terminal kinase 1/2 (JNK1/2) or p38
      MAPK. CONCLUSION: The hsp70.1-deficient mice did not show any significant changes
      in terms of cell proliferation, apoptosis, or stress response due to exposure of
      849 or 1,763 MHz RF fields.

PMID- 16449087
TI  - Inpatient initiation of buprenorphine maintenance vs. detoxification: can
      retention of opioid-dependent patients in outpatient counseling be improved?
AB  - Buprenorphine-naloxone is an office-based opioid agonist released in 2003 in the
      United States for the maintenance of heroin- and other opioid-dependent patients.
      Concern has been raised that the medication will distract or otherwise inhibit
      patients from participating in a holistic recovery program or abstinence-based
      counseling. Using a retrospective chart review, the first thirty opioid-dependent
      patients induced on buprenorphine maintenance therapy in an inpatient
      detoxification unit were compared to thirty age- and gender-matched patients who
      underwent detoxification (with a tramadol taper) and referral to intensive
      outpatient treatment. The clinical outcomes were a comparison of completion rates
      for an intensive outpatient program (IOP) and retention in treatment after twelve
      weeks of aftercare therapy. Patients induced on buprenorphine maintenance over
      three days had similar relief of withdrawal symptoms to patients detoxified from
      opioids over five days with tramadol. Patients maintained on buprenorphine had a
      markedly increased initiation of IOP and remained in outpatient treatment longer
      than patients who were detoxified (8.5 wks vs. 0.4 wks, p < 0.001). This study
      indicates that induction and maintenance on buprenorphine may be more effective
      than detoxification for engaging and retaining patients in abstinence-based
      comprehensive outpatient addiction treatment.

PMID- 16449088
TI  - Cannabis withdrawal among non-treatment-seeking adult cannabis users.
AB  - This study investigates the clinical significance of a cannabis withdrawal
      syndrome in 104 adult, non-treatment-seeking, primarily cannabis users who
      reported at least one serious attempt to stop using cannabis. Retrospective self
      report data were obtained on eighteen potential cannabis withdrawal symptoms
      derived from the literature, including co-occurrence, time course, and any
      actions taken to relieve the symptom. Study findings provide evidence for the
      clinical significance of a cannabis withdrawal syndrome, based on the high
      prevalence and co-occurrence of multiple symptoms that follow a consistent time
      course and that prompt action by the subjects to obtain relief, including serving
      as negative reinforcement for cannabis use.

PMID- 16449089
TI  - Return to smoking following a smoke-free psychiatric hospitalization.
AB  - This study examined the smoking behaviors and motivations of 100 patients
      hospitalized in a smoke-free psychiatry unit. The sample averaged nineteen
      cigarettes per day and had a history of repeated failed quit attempts, yet 65%
      expressed interest in quitting. During hospitalization, nicotine replacement was
      provided to 70% of smokers to manage nicotine withdrawal. Provider counseling for
      smoking cessation, however, was rare, and all patients returned to smoking within
      five weeks of hospital discharge. The inpatient setting provides a potential site
      for initiating tobacco dependence treatment; however to maintain abstinence
      following hospital discharge, greater support is needed.

PMID- 16449090
TI  - Drug interactions between opioids and antiretroviral medications: interaction
      between methadone, LAAM, and delavirdine.
AB  - Understanding the drug interactions between antiretrovirals and opioid therapies
      may decrease toxicities and enhance adherence with improved HIV outcomes in
      opioid-dependent individuals. The authors report the results of a clinical
      pharmacology study designed to determine whether significant pharmacokinetic
      and/or pharmacodynamic interactions occur between the non-nucleoside reverse
      transcriptase inhibitor, delavirdine (DLV), and either methadone or levo-alpha
      acetyl methadol (LAAM) (n = 40). DLV significantly decreased methadone clearance
      (p = .018) and increased the methadone elimination half-life (p < .001) with a
      resultant increase in AUC of 19% and C(min)of 29%. The combined effect of DLV on
      the total concentration of LAAM and its active metabolites, norLAAM and
      dinorLAAM, was to significantly increase AUC by 43% (p < .001), C(max) by 30% (p
      = .013), and C(min) by 59% (p = .004) while decreasing T(max) (p = .05).
      Cognitive deficits over the seven-day study period as measured by the Mini-Mental
      State Examination, opioid withdrawal symptoms as measured by the Objective Opioid
      Withdrawal Scale, or complaints of adverse symptoms were not observed. Methadone
      and LAAM did not affect DLV concentrations. The findings from this study show
      that DLV treatment in methadone- or LAAM-maintained individuals results in
      altered opioid pharmacokinetics with an increased exposure and potential risk for
      opioid toxicity with methadone or LAAM treatment and an increased risk of cardiac
      toxicity with concomitant LAAM and DLV administration.

PMID- 16449091
TI  - Lifetime histories of trauma among pathological gamblers.
AB  - This study extends the work completed with pathological gamblers and substance
      abusers, looking at associations between a history of trauma and comorbid
      substance dependence, impulsivity, measures of problem severity, and personality
      variables. We studied 111 patients admitted to the gambling treatment program at
      the Brecksville VA Medical Center and found that 64% of gamblers reported a
      history of emotional trauma; 40.5%, physical trauma; and 24.3%, sexual trauma.
      Most of this trauma occurred in childhood. A history of trauma was associated
      with a greater relative frequency of suicide attempts and drug and alcohol
      dependence, more severe scores in measures of psychiatric distress, and limited
      effects on personality functioning.

PMID- 16449092
TI  - Atypical antipsychotic medication and substance use-related outcomes in the
      treatment of schizophrenia.
AB  - Using national administrative data from the Department of Veterans Affairs (VA),
      clinical change in veterans with schizophrenia and comorbid substance abuse and
      dependence (n = 249) was assessed with the Addiction Severity Index. Outcomes
      among those switched or maintained on an atypical antipsychotic were compared
      with those treated with conventionals. For the entire sample and those on an
      atypical during the last assessment, paired t-tests showed significant decreases
      in the alcohol and psychological ASI scores. However, multivariate analysis
      showed no greater improvement in alcohol, drug, or psychological scores in
      individuals who were switched to (n = 33) or maintained on (n = 161) an atypical
      antipsychotic as compared to those who were treated with conventional at the
      final assessment (n = 55). Patients treated with atypical antipsychotics achieved
      no greater improvement in substance-related outcomes that patients who were not.

PMID- 16449093
TI  - The role of twelve-step approaches in dual diagnosis treatment and recovery.
AB  - The authors reviewed the empirical literature concerning the use of twelve-step
      programs and treatments by patients with co-occurring substance use disorders and
      other psychiatric disorders. Strong evidence was found that dually diagnosed
      individuals (DDI), with the possible exception of those with psychotic disorders,
      attend twelve-step programs at rates comparable to non-DDI. Twelve-step
      involvement is consistently associated with improved substance use outcomes.
      Although there have been numerous clinical trials involving twelve step-oriented
      interventions for DDI, most of the studies suffered from substantial
      methodological limitations. More work is needed to determine what kinds of twelve
      step treatments and programs are effective for various types of patients and
      elucidate the mechanisms by which these approaches facilitate recovery.

PMID- 16449094
TI  - Transferring methadone-stabilized pregnant patients to buprenorphine using an
      immediate release morphine transition: an open-label exploratory study.
AB  - A transition from methadone to buprenorphine without intervening withdrawal
      symptoms is critical for advancing the treatment of opioid-dependent patients.
      Four pregnant inpatients were transferred from methadone (65-85 mg) to five days
      of immediate release morphine (IRM) and then to buprenorphine (12-28 mg).
      Withdrawal scores decreased during the five days of IRM and subsequently
      increased over the first three days on buprenorphine. The transitional use of IRM
      appears safe for both mother and fetus. Withdrawal symptoms appeared during
      buprenorphine induction; however, these data suggest that the intensity of
      withdrawal symptoms may be lessened by the dose and frequency of buprenorphine
      administration.

PMID- 16449095
TI  - The effects of alcohol and drug dependence on the course of depression.
AB  - There is a paucity of epidemiological data regarding the effects of substance use
      dependence (SUD) on the course of depression. This study analyzed data from the
      National Comorbidity Survey (NCS). Among respondents with lifetime SUD and
      unipolar depression, current SUD increased the risk (OR = 2.9) of past year
      depression and anxiety disorders (OR = 2.2).

PMID- 16449097
TI  - A comparison of two versions of the clinical institute withdrawal assessment for
      alcohol: the CIWA-Ar and CIWA-AD.
AB  - Scores from two versions of the Clinical Institute Withdrawal Assessment for
      Alcohol, the CIWA-Ar and CIWA-AD, were compared in 135 alcohol detoxification
      episodes. The paired mean score for withdrawal severity was statistically higher
      with the CIWA-AD (p < 0.001), but the mean difference of 0.45 (95% CI: 0.38-0.53,
      t = 11.74) is not likely to be clinically significant. The difference in the
      total score between the two scales was 1 point or less 82.6% of the time, and
      nearly all (97.7%) of the CIWA-AD scores were within 3 points of the paired CIWA
      Ar score (range - 6 to + 6).

PMID- 16449096
TI  - A randomized, open-label, controlled trial of gabapentin and phenobarbital in the
      treatment of alcohol withdrawal.
AB  - Gabapentin was compared with phenobarbital for the treatment of alcohol
      withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There
      were no significant differences in the proportion of treatment completers between
      treatment groups or the proportion of patients in each group requiring rescue
      medication for breakthrough signs and symptoms of alcohol withdrawal. There were
      no significant treatment differences in withdrawal symptoms or psychological
      distress, nor were there serious adverse events. These findings suggest that
      gabapentin may be as effective as phenobarbital in the treatment of alcohol
      withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study
      of its effectiveness in treating alcohol withdrawal is warranted.

PMID- 16449098
TI  - Club drug use among youths in treatment for substance abuse.
AB  - We describe lifetime rates of club drug use among 782 youths in treatment for
      substance abuse. Rates (%) for youths under eighteen (N = 486) were
      methylenedioxymethamphetamine (MDMA), 32.3; gamma-hydroxybutyrate (GHB), 7.0;
      lysergic acid diethylamide (LSD), 48.6; ketamine, 18.3; and methamphetamine,
      30.2. For youths 18-32 (N = 289) rates (%) were MDMA, 37.0; GHB, 13.1; LSD, 42.9;
      ketamine, 17.0; and methamphetamine, 31.5. Older youths reported significantly
      more use of GHB than younger youths (p < .01). Youths reported using club drugs
      frequently outside of rave settings. Club drug use is common among youths in
      treatment for substance abuse and has spread beyond the rave culture.

PMID- 16449099
TI  - Study of the efficacy of fluoxetine and clomipramine in the treatment of
      premature ejaculation after opioid detoxification.
AB  - Premature ejaculation is a common symptom that can provoke relapse in formerly
      opioid-dependent men after detoxification. The purpose of this study was to
      compare the efficacy of clomipramine and fluoxetine for the treatment of
      premature ejaculation in formerly opioid-dependent men after detoxification.
      Sixty opium-detoxified men with A & B DSM-IV diagnostic criteria for premature
      ejaculation participated in a prospective two-week descriptive inferential
      clinical trial after a two-week washout period. The subjects did not consume any
      other medications but naltrexone for maintenance of an opium-free state. The
      subjects were randomly divided into two groups of thirty subjects, one group
      received fluoxetine (10 mg/d for the first and 20 mg/d for the second week), and
      the other received clomipramine (25 mg/d for the first and 50 mg/d for the second
      week). Twenty five subjects did not continue the treatment and were lost to
      follow-up. The severity of the premature ejaculation was graded regarding the
      subjects' report in weeks 0, 1, and 2. Mann Whitney-U and Wilcoxon non-parametric
      tests were used for statistical analysis. Fluoxetine (10 mg/d then 20 mg/d) and
      clomipramine (25 mg/d then 50 mg/d) were both effective in the treatment of
      premature ejaculation and did not show any difference in efficacy. The severity
      of premature ejaculation did not show any relation to the subjects' age,
      education level, opioid type, or route of abuse. Fluoxetine and clomipramine both
      can be equally used in the treatment of premature ejaculation following opioid
      detoxification, depending on their side effects and other symptoms in the
      subjects.

PMID- 16449102
TI  - At-home fetal DNA gender testing: caveat emptor.

PMID- 16449100
TI  - Safety and tolerability of N-acetylcysteine in cocaine-dependent individuals.
AB  - A double-blind placebo-controlled crossover Phase I trial was conducted to assess
      the safety and tolerability of N-Acetylcysteine (NAC) in healthy, cocaine
      dependent humans. Thirteen participants attended a three-day hospitalization in
      which they received placebo or NAC. Subjects were crossed over to receive the
      opposite medication condition during a second three-day hospitalization, which
      occurred the following week. Across placebo and NAC conditions, only mild side
      effects were noted, and the number of subjects reporting side effects did not
      differ. There were trends for a greater reduction in withdrawal symptoms and
      craving within the NAC condition. These preliminary results suggest that NAC is
      well tolerated in healthy, cocaine-dependent individuals and may reduce cocaine
      related withdrawal symptoms and craving.

PMID- 16449103
TI  - Cerclage: we all know how to do it but can't agree when to do it.

PMID- 16449104
TI  - Management of cervical insufficiency and bulging fetal membranes.
AB  - OBJECTIVE: To evaluate the efficacy of emergency cerclage in cases with dilated
      cervix and protruding fetal membranes in a group of women considered at low risk
      for preterm delivery by their obstetric histories. METHODS: All cases of cervical
      dilatation and bulging membranes were detected through a transvaginal
      ultrasonographic screening for preterm delivery between 18 and 26 weeks during a
      6-year study period. Twenty-nine women underwent an emergency cervical cerclage
      and composed the cerclage group, whereas 17 others refused and formed the bed
      rest group. All patients were given antibiotics and prophylactic tocolysis.
      RESULTS: The mean prolongation of pregnancy (8.8 weeks) and the mean birth weight
      (2,101 g) after cerclage placement differed significantly from those of the bed
      rest group (3.1 weeks and 739 g, respectively). Twenty-five of the 29 pregnancies
      in the cerclage group ended in live birth, compared with 7 of the 17 pregnancies
      in the bed rest group (P = .001) (relative risk [RR] 0.33, 95% confidence
      interval [CI] 0.11-0.98). Neonatal survival was 96% in the cerclage group and
      57.1% in the bed rest group (P = .025) (RR 0.09, 95% CI 0.01-0.76). The preterm
      delivery rate less than 32 weeks was 31% and 94.1% in the cerclage and the bed
      rest groups, respectively (P < .001) (RR 0.33, 95% CI 0.19-0.57), whereas the
      admission to neonatal intensive care unit was 28% and 85.7% in the 2 groups,
      respectively, (P = .01) (RR 0.33, 95% CI 0.16-0.66). CONCLUSION: Emergency
      cervical cerclage can be accomplished safely in women with dilated cervix and
      bulging membranes. It can reduce preterm delivery before 32 weeks and improve
      neonatal survival compared with bed rest. LEVEL OF EVIDENCE: II-1.

PMID- 16449105
TI  - Clinical and ultrasound parameters to predict the risk of cesarean delivery after
      induction of labor.
AB  - OBJECTIVE: To evaluate whether factors in the maternal history and/or ultrasound
      parameters are useful in predicting the risk of cesarean delivery after induction
      of labor. METHODS: Maternal age, height, body mass index, parity, gestational
      age, Bishop score, ultrasonic amniotic fluid volume, fetal head position,
      estimated fetal weight, and transvaginal cervical length were studied
      prospectively in 267 women at 36 or more weeks of gestation immediately before
      induction of labor. Logistic regression analysis was used to determine which
      factors best predicted the risk of cesarean delivery. Receiver operating
      characteristic curves and a resampling technique were used to evaluate the
      model's performance. RESULTS: Eighty (30%) of these 267 women had cesarean
      delivery. Logistic regression was performed and a final model chosen, which
      included parity (odds ratio [OR] 20.56, 95% confidence interval [CI] 7.97-53.05,
      P < .001), body mass index (OR 6.17, 95% CI 2.10-18.13, P < .001), height (OR
      0.94, 95% CI 0.89-0.98, P = .005), and ultrasonic transvaginal cervical length
      (OR 1.07, 95% CI 1.04-1.11, P < .001) as the best predictors of cesarean
      delivery. A risk score was calculated containing these 4 parameters, which
      predicted reasonably accurately the risk of cesarean delivery. CONCLUSION:
      Parity, body mass index, height, and ultrasonic transvaginal cervical length are
      the most accurate parameters in predicting the risk of cesarean delivery after
      induction of labor. A predictive model using these would allow more accurate
      counseling and better informed consent in the decision-making process regarding
      induction of labor LEVEL OF EVIDENCE: II-2.

PMID- 16449106
TI  - Induction of labor using a foley balloon, with and without extra-amniotic saline
      infusion.
AB  - OBJECTIVE: To compare transcervical Foley bulb with and without extra-amniotic
      saline infusion for induction of labor in patients with an unfavorable cervix.
      METHODS: Women who presented for induction of labor with Bishop score less than 5
      were randomly assigned to receive Foley alone or Foley with extra-amniotic saline
      infusion for induction of labor. Primary outcome was time from start of induction
      to vaginal delivery. Secondary outcomes were cesarean delivery rates, incidence
      of chorioamnionitis, Apgar scores at 1 and 5 minutes, and adverse events.
      RESULTS: One hundred forty women completed the study. Time from induction to
      vaginal delivery was 16.58 (+/- 7.55) hours in the extra-amniotic saline infusion
      group compared with 21.47 (+/- 9.95) hours in the Foley group (P < .01).
      Chorioamnionitis occurred in 4 of 66 (6.1%) women in the extra-amniotic saline
      infusion group compared with 12 of 74 (16.2%) women in the Foley group (P =
      .067). Cesarean delivery rate was 21.2% versus 20.1% in the extra-amniotic saline
      infusion and Foley groups, respectively (P = 1.0). Median 1-minute and 5-minute
      Apgar scores were 9 in both groups. Adverse events were rare and unrelated to
      method of induction. CONCLUSION: Induction of labor by using Foley with extra
      amniotic saline infusion results in shorter induction-to-vaginal-delivery time
      than Foley alone, without affecting cesarean delivery rates. LEVEL OF EVIDENCE:
      II-I

PMID- 16449107
TI  - Results of a well-defined protocol for a trial of labor after prior cesarean
      delivery.
AB  - OBJECTIVE: It has been claimed that a trial of labor after cesarean carries
      higher maternal and fetal risks than planned cesarean delivery. Because the
      management of such patients in our department differs from that described in some
      studies, and is perhaps more cautious, we hypothesized that the outcome may be
      better. METHODS: We identified women with 1 previous low uterine segment cesarean
      who had delivered a cephalic singleton infant at gestational age 34 weeks or more
      from January 2000 through May 2005. Our policy is to encourage such women to
      undergo a trial of labor unless cesarean delivery is indicated. Unless otherwise
      indicated, our policy is to wait for spontaneous labor. We do not use
      prostaglandins, and recommend cesarean delivery if the cervix is unripe.(Bishop
      score < 6). We compared the outcome between women who underwent a trial of labor
      and women who underwent planned cesarean delivery. RESULTS: A trial of labor was
      attempted by 841 women (80% successful), and 467 underwent planned cesarean
      delivery. Uterine rupture was observed in 1 woman 18 hours after vaginal
      delivery. There was no difference in major or minor maternal morbidity. There was
      no serious neonatal morbidity. Among the planned cesarean patients, hospital stay
      was longer, and there were more admissions to the neonatal intensive care unit.
      CONCLUSION: With our well-defined protocol, a trial of labor after cesarean seems
      to be as safe for the mother and infant as planned cesarean delivery, and the
      hospital stay is shorter. LEVEL OF EVIDENCE: II-2.

PMID- 16449108
TI  - Black cohosh and St. John's wort for climacteric complaints: a randomized trial.
AB  - OBJECTIVE: To investigate the efficacy of the fixed combination of black cohosh
      (Cimicifuga racemosa) and St. John's wort (Hypericum perforatum) extracts in
      women with climacteric complaints with a pronounced psychological component.
      METHODS: In this double-blind randomized placebo-control study, 301 women
      experiencing climacteric complaints with psychological symptoms were treated with
      ethanolic St. John's wort extract and isopropanolic black cohosh extract or a
      matched placebo for 16 weeks. Climacteric complaints were evaluated by means of
      the Menopause Rating Scale mean score, and psychological complaints were
      evaluated using the Hamilton Depression Rating Scale sum score. RESULTS: The mean
      (+/- standard deviation) Menopause Rating Scale score decreased 50% (0.46 +/-
      0.13 to 0.23 +/- 0.13) in the treatment group and 19.6% (0.46 +/- 0.14 to 0.37 +/
      0.15) in the placebo group. The Hamilton Depression Rating Scale total score
      decreased 41.8% in the treatment group (18.9 +/- 2.2 to 11.0 +/- 3.8 points), and
      12.7% in the placebo group (18.9 +/- 2.1 to 16.5 +/- 4.3). The treatment was
      significantly (P < .001) superior to placebo in both measures. There were no
      relevant group differences regarding adverse events, laboratory values, or
      tolerability. CONCLUSION: This fixed combination of black cohosh and St. John's
      wort is superior to placebo in alleviating climacteric complaints, including the
      related psychological component. LEVEL OF EVIDENCE: I.

PMID- 16449109
TI  - Surgical treatment for the vulvar vestibulitis syndrome.
AB  - OBJECTIVE: To study the outcome and complications of surgical treatment for
      vulvar vestibulitis syndrome and to identify patient characteristics that may
      have influenced the outcome. METHODS: Relevant patient characteristics were
      extracted retrospectively from the medical records of 155 women aged 40 years or
      younger who had received surgical treatment for vulvar vestibulitis syndrome. To
      assess outcome and complications, 126 of these 155 women (81%) participated in a
      telephone interview, conducted 1 to 4 years after surgery. RESULTS: After surgery
      93% of the patients could have sexual intercourse compared with 78% before
      surgery; this increase was statistically significant (Mantel-Haenszel odds ratio
      3.43, 95% confidence interval [CI] 1.48-7.96). In 62% of the women (95% CI 53
      70%), sexual intercourse was painless after surgery. Eighty-nine percent (95% CI
      84-95%) would recommend surgical treatment to other women experiencing vulvar
      vestibulitis syndrome. There were no major complications. Decreased lubrication
      during sexual arousal was the most frequently reported adverse effect (24%, 95%
      CI 16-32%), followed by the development of a Bartholin's cyst (6%, 95% CI 2-10%).
      More of the women aged 30 years or younger reported that they could have sexual
      intercourse after surgery, and more of them would recommend surgical treatment to
      other patients than women aged 31 years or older. CONCLUSION: Surgical treatment
      for vulvar vestibulitis syndrome achieved high success rates with an acceptable
      rate of complications. Age of 30 years or younger was associated with a better
      outcome. LEVEL OF EVIDENCE: III.

PMID- 16449110
TI  - Humidified compared with dry, heated carbon dioxide at laparoscopy to reduce
      pain.
AB  - OBJECTIVE: To study whether using 95% humidified, heated carbon dioxide (CO(2))
      at laparoscopy reduces pain compared with dry, heated CO(2). METHODS: Patients
      were randomly assigned to either heated, 95% humidified CO(2) (study group) or
      heated, dry CO(2) (control group) during laparoscopy. Pain control was achieved
      per standard protocols. Pain scales were administered the first 4 hours and 24
      and 48 hours postoperatively. RESULTS: The 89 patients available in the intent-to
      treat model revealed a decrease in total morphine equivalents and a decrease in
      pain scores at 1, 2, and 24 hours in the study group (directional P values <
      .05). Subgroup analysis in patients without chronic pelvic pain revealed lower
      mean pain scores at 1, 2, 24, and 48 hours and decreases in postoperative and
      total morphine equivalents (directional P values < .05) in the study group.
      CONCLUSION: At laparoscopy, heated, 95% humidified CO(2) effectively decreases
      postoperative pain and narcotics usage compared with heated, dry CO(2). LEVEL OF
      EVIDENCE: II-2.

PMID- 16449111
TI  - Four percent intrauterine lidocaine infusion for pain management in first
      trimester abortions.
AB  - OBJECTIVE: To study the effects of a 4% intrauterine lidocaine infusion on
      perceived patient pain in first-trimester abortions. METHODS: A randomized,
      double-blind, placebo-controlled trial of 80 women receiving either a 5-mL 4%
      lidocaine (n = 40) or saline (n = 40) intrauterine infusion and a standard
      paracervical block before first-trimester abortion. Women completed a series of
      100-mm visual analog scales (anchors: 0 = none, 100 mm = worst imaginable) to
      measure their perceived pain (anticipated pain, after speculum insertion, after
      intrauterine infusion, after cervical dilation, after suction aspiration, and 30
      minutes postprocedure). Eight women volunteered for serum lidocaine levels after
      the lidocaine infusion. RESULTS: Groups were similar in respect to age, parity,
      prior abortion, ethnicity, gestational age, and level of dysmenorrhea. Pain
      scores demonstrated a significant difference between groups during cervical
      dilation (saline 55 mm +/- 26, lidocaine 35 mm +/- 30, P < .01) and during
      aspiration (saline 71 mm +/- 20, lidocaine 43 mm +/- 30, P < .01). The lidocaine
      group reported significantly more symptoms (ie, oral numbness and tingling) than
      the saline group (saline 0/39, lidocaine 16/38, 42%, P < .01). The highest serum
      lidocaine level recorded was 4.0 microg/mL (lidocaine group). There was no
      difference in overall satisfaction between the 2 groups. CONCLUSION: Compared
      with paracervical block alone, the addition of a 4% intrauterine lidocaine
      infusion resulted in a significant reduction in patient perception of pain during
      first-trimester abortion. Although subjective symptoms of systemic lidocaine
      effect were common, no subjects demonstrated serum levels consistent with
      lidocaine toxicity. However, further studies to determine safety are needed.
      LEVEL OF EVIDENCE: I.

PMID- 16449112
TI  - Risk factors for hyperemesis gravidarum requiring hospital admission during
      pregnancy.
AB  - OBJECTIVE: To identify risk factors for hyperemesis requiring hospital admission
      during pregnancy. METHODS: Data from a population-based cohort of all deliveries
      in Nova Scotia, Canada between 1988 and 2002 were obtained from the Nova Scotia
      Atlee Perinatal Database. Women with 1 or more antepartum admissions for
      hyperemesis were compared with women with no admissions for hyperemesis. Relative
      risks (RRs) and 95% confidence intervals (CIs) were estimated using logistic
      regression and used to determine a set of independent risk factors for
      hyperemesis. RESULTS: The overall rate of admission for hyperemesis was 0.8% (n =
      1,301) among 157,922 deliveries. In the adjusted analysis, hyperthyroid disorders
      (RR 4.5, 95% CI 1.8-11.1), psychiatric illness (RR 4.1, 95% CI 3.0-5.7), previous
      molar pregnancy (RR 3.3, 95% CI 1.6-6.8), preexisting diabetes (RR 2.6, 95% CI
      1.5-4.7), gastrointestinal disorders (RR 2.5, 95% CI 1.8-3.6), and asthma (RR
      1.5, 95% CI 1.2-1.9) were all statistically significant risk factors for
      hyperemesis, whereas maternal smoking and maternal age older than 30 were
      associated with decreased risk. Compared with singleton male pregnancies,
      singleton female pregnancies, pregnancies with multiple male fetuses, and male
      and female combinations were associated with statistically significant increased
      risk of hyperemesis. CONCLUSION: Although hospitalization for hyperemesis occurs
      in less than 1% of pregnant women, this translates to a large number of hospital
      admissions. The factors associated with hyperemesis are primarily medical and
      fetal factors that are not easily modifiable, but identification of these factors
      may be useful in determining those women at high risk for developing hyperemesis.
      LEVEL OF EVIDENCE: II-2.

PMID- 16449113
TI  - Outcomes of pregnancies complicated by hyperemesis gravidarum.
AB  - OBJECTIVE: To evaluate maternal and neonatal outcomes among women with
      hyperemesis during pregnancy. METHODS: A population-based retrospective cohort
      study was conducted among women with singleton deliveries between 1988 and 2002.
      Hyperemetic pregnancies were defined as those requiring one or more antepartum
      admissions for hyperemesis before 24 weeks of gestation. Severity of hyperemesis
      was evaluated according to the number of antenatal hospital admissions (1 or 2
      versus 3 or more) and according to weight gain during pregnancy (< 7 kg [15.4 lb]
      versus > or = 7 kg). Maternal outcomes evaluated included weight gain during
      pregnancy, gestational diabetes, gestational hypertension, labor induction, and
      cesarean delivery. Neonatal outcomes included 5-minute Apgar score of less than
      7, low birth weight, small for gestational age, preterm delivery, and perinatal
      death. Logistic regression was used to generate adjusted odds ratios for all
      outcomes, and the odds ratios were converted to relative risks. RESULTS: Of the
      156,091 singleton pregnancies, 1,270 had an admission for hyperemesis. Compared
      to women without hyperemesis, infants born to women with hyperemesis and with low
      pregnancy weight gain (< 7 kg [15.4 lb]) were more likely to be low birth weight,
      small for gestational age (SGA), born before 37 weeks of gestation, and have a 5
      minute Apgar score of less than 7. Compared with infants born to women without
      hyperemesis, rates of low birth weight and preterm delivery were substantially
      higher among infants born to women with hyperemesis and low pregnancy weight gain
      (4.2% versus 12.5% and 4.9% versus 13.9%, respectively). The outcomes among
      infants born to women with hyperemesis with pregnancy weight gain of 7 kg (15.4
      lb) or more were not different from the outcomes among women without hyperemesis.
      CONCLUSION: The results of this study suggest that the adverse infant outcomes
      associated with hyperemesis are a consequence of, and mostly limited to, women
      with poor maternal weight gain. LEVEL OF EVIDENCE: II-2.

PMID- 16449114
TI  - Early risk factors for pregnancy loss in lupus.
AB  - OBJECTIVE: To identify early risk factors for pregnancy loss in lupus
      pregnancies. METHODS: We conducted a cohort study of all pregnancies seen in the
      first trimester in lupus patients followed from 1987 to 2002 at the Hopkins Lupus
      Center. At each visit, vital signs, a complete blood count, a urinalysis, and a
      24-hour urine collection for total protein, if the dipstick revealed proteinuria,
      were obtained. Proteinuria was defined as protein greater than 500 mg in a 24
      hour urine collection. Secondary antiphospholipid syndrome was diagnosed by using
      the Sapporo criteria. Thrombocytopenia was defined as platelets under 150,000.
      Hypertension was defined as blood pressure over 140/90 mm Hg during the first
      trimester. Pregnancies electively terminated were excluded from this study.
      RESULTS: One hundred sixty-six pregnancies in 125 women were followed in the
      Hopkins Lupus Cohort from the first trimester onward. Twenty-seven pregnancies
      (16%) ended with a loss. Pregnancy loss was increased 2.6 times in women with
      first-trimester proteinuria (P = .04). A diagnosis of secondary antiphospholipid
      syndrome led to a 3.1-fold increase in pregnancy loss, predominantly after 20
      weeks of gestation (P = .004). Thrombocytopenia in the first trimester led to an
      increase in pregnancy loss by 3.3 fold (P < or = .001). First-trimester
      hypertension led to a 2.4-fold increase in pregnancy loss (P = .027). Each risk
      factor was independent in raising pregnancy loss risk. CONCLUSION: The acronym
      PATH can help remind clinicians to monitor for Proteinuria, Antiphospholipid
      syndrome, Thrombocytopenia, and Hypertension early in pregnancy. Close
      observation, with frequent laboratory analysis and appropriate therapy, is
      important to pregnancy success in women with lupus. LEVEL OF EVIDENCE: II-2.

PMID- 16449115
TI  - Association between low day 16 hCG and miscarriage after proven cardiac activity.
AB  - OBJECTIVE: To investigate an association between low human chorionic
      gonadotrophin (hCG) levels at the end of the first week of implantation and later
      clinical miscarriage occurring after ultrasound confirmation of a live pregnancy.
      METHODS: This was an observational retrospective study of 1,054 women who
      underwent in vitro fertilization and achieved an ultrasound-confirmed live
      singleton pregnancy with cardiac activity. The incidence of miscarriage diagnosed
      at 8-19 weeks +6 days of gestation was estimated in these 3 subgroups according
      to their hCG concentrations at day 16 after conception: less than the 25th, 25th
      75th, and more than the 75th percentiles. RESULTS: The overall incidence of
      miscarriage was 11.1% (117/1,054), and the median gestational age at diagnosis
      was 10 weeks and 4 days. The median (95% confidence interval) day 16 hCG level in
      the miscarriage group was 182 mIU/mL (157-211), significantly lower than the
      median level in those who had an ongoing pregnancy (223 mIU/mL [213-233], P <
      .003). There was an increasing risk of miscarriage associated with decreased hCG
      levels (8.0% at > 75th percentile; 9.9% at 25th-75th percentiles; 16.7% at < 25th
      percentile; P = .003). CONCLUSION: Low hCG levels in very early pregnancy are
      associated with an increased risk of miscarriage occurring after the clinical
      recognition of pregnancy. The mechanisms underlying late first-trimester and
      second-trimester miscarriages may have begun as early as the first week of
      implantation. LEVEL OF EVIDENCE: III.

PMID- 16449116
TI  - Postoperative activity restrictions: any evidence?
AB  - OBJECTIVE: Because of a widespread but untested belief that increased intra
      abdominal pressure contributes to pelvic floor disorders, physicians commonly
      restrict various activities postoperatively. Our aim was to describe intra
      abdominal pressures during common physical activities. METHODS: Thirty women of
      wide age and weight ranges who were not undergoing treatment for pelvic floor
      disorders performed 3 repetitions of various activities while intra-abdominal
      pressures (baseline and maximal) were approximated via microtip rectal catheters.
      We calculated median peak and net pressures (centimeters of H(2)O). We assessed
      correlations between abdominal pressures and body mass index, abdominal
      circumference, and grip strength (a proxy for overall strength). P < .025 was
      considered significant. RESULTS: Median peak abdominal pressures ranged from 48
      (lifting 8 lb from a counter) to 150 (lifting 35 lb from the floor), with much
      variation. Many activities did not raise the intra-abdominal pressure more than
      simply getting out of a chair, including lifting 8, 13, and 20 lb from a counter,
      lifting 8 or 13 lb from the floor, climbing stairs, walking briskly, or doing
      abdominal crunches. Body mass index and abdominal circumference each correlated
      positively with peak, but not net, pressures. Age and grip strength were not
      associated with abdominal pressure. CONCLUSION: Some activities commonly
      restricted postoperatively have no greater effect on intra-abdominal pressures
      than unavoidable activities like rising from a chair. How lifting is done impacts
      intra-abdominal pressure. Many current postoperative guidelines are needlessly
      restrictive. Further research is needed to determine whether increased intra
      abdominal pressure truly promotes pelvic floor disorders. LEVEL OF EVIDENCE: III.

PMID- 16449117
TI  - Single-dose fluconazole for vulvovaginal candidiasis: impact on prothrombin time
      in women taking warfarin.
AB  - OBJECTIVE: To estimate the effect of a single oral 150-mg dose of fluconazole on
      the prothrombin time of women on long-term warfarin therapy. METHODS: Women on
      warfarin therapy for 6 months or more with no change in dose within 4 weeks of
      the study, and a prothrombin time (PT) with an International Normalized Ratio
      (INR) between 2 and 3 were invited to participate. Two consecutive baseline PTs
      were obtained (days -1 and 0), and women were given 150 mg of fluconazole.
      Prothrombin times were measured on days 2, 5, and 8 of the study. The change in
      PT was calculated from the difference between the baseline PT on day 0 and the PT
      during the study period. To detect a 10% difference in a PT (approximately 2.1
      seconds) of a patient with an INR of 2.0, at P < .05 and a power of 90%, 5
      subjects are required. RESULTS: Six women participated. The mean (+/- standard
      deviation) PT for day 0 was 27.7 +/- 4.1 seconds or INR 2.6 +/- 0.4. The PT
      increased 11% at day 2, 34% at day 5, and 2% at day 8; these differences were not
      statistically significant. However, one half of the women had either a clinically
      relevant increase of the INR greater than 4, or bleeding that required their
      dosage of warfarin to be decreased. CONCLUSION: A single 150-mg oral dose of
      fluconazole may increase the PT to a clinically relevant level in a woman on
      chronic warfarin therapy. Clinicians should monitor the PT carefully after a
      single dose of fluconazole. LEVEL OF EVIDENCE: II-2.

PMID- 16449118
TI  - Cervical intraepithelial neoplasia and cervicovaginal shedding of human
      immunodeficiency virus.
AB  - OBJECTIVE: Although human immunodeficiency virus (HIV) infection is a well-known
      risk factor for cervical intraepithelial neoplasia (CIN), the influence of CIN on
      cervicovaginal shedding of HIV is poorly understood. The purpose of this study
      was to evaluate the association between CIN and the shedding of HIV in
      cervicovaginal secretions. METHODS: Two hundred sixteen HIV-seropositive patients
      were followed up by Pap test, colposcopy, and targeted cervical biopsies for a
      median of 16 months (range 0-94). A diagnosis of low-grade CIN was made on the
      basis of Pap test and either colposcopy or cervical biopsy. High-grade CIN was
      diagnosed solely on the basis of cervical biopsy. At each follow-up visit, we
      measured HIV-1 RNA in plasma, proviral HIV-1 DNA, and cell-associated and cell
      free HIV-1 RNA in cervicovaginal secretion by competitive polymerase chain
      reaction (cRT-PCR) and reverse transcriptase PCR. The univariable and
      multivariable associations between the occurrence of CIN and the presence of HIV
      related nucleic acids in cervicovaginal secretions were evaluated with logistic
      generalized estimating equations. RESULTS: Overall, at enrollment and during the
      follow-up period, a diagnosis of either low-grade or high-grade CIN was made in
      14.4% (99/689) and 6.7% (46/689) of the visits, respectively. The presence of
      measurable levels of plasma HIV-1 RNA was a significant risk factor for the
      detection of cervicovaginal HIV-1 DNA (odds ratio [OR] 1.86, 95% confidence
      interval [CI] 1.32-2.61, P < .001), cell-associated (OR 1.69, 95% CI 1.18-2.43, P
      = .004), and cell-free HIV-1 RNA (OR 1.84, 95% CI 1.28-2.63, P = .001). After the
      adjustment for the effect of plasma HIV-1 RNA, CD4(+) positive cell counts less
      than 200 mm(3), and bacterial vaginosis, the detection of cell-associated (OR
      1.75, 95% CI 1.23-2.49, P = .006) and cell-free HIV-1 RNA (OR 2.0, 95% CI 1.39
      2.87, P = .001) in cervicovaginal secretions was significantly associated with
      the diagnosis of CIN. CONCLUSION: The presence of CIN lesions is a significant
      risk factor for genital HIV shedding. Given the high prevalence of cervical
      disease among HIV-positive women, this finding could have important
      epidemiological implications in both heterosexual and perinatal transmission of
      HIV. LEVEL OF EVIDENCE: II-2.

PMID- 16449119
TI  - Cost-effectiveness of extending cervical cancer screening intervals among women
      with prior normal pap tests.
AB  - OBJECTIVE: Annual cervical cancer screening in women with many prior normal Pap
      tests is common despite limited evidence on the cost-effectiveness of this
      strategy. We estimated the cost-effectiveness of screening women with 3 or more
      prior normal tests compared with screening those with no prior tests. METHODS: We
      used a validated cost-effectiveness model in conjunction with data on the
      prevalence of biopsy-proven cervical neoplasia in women enrolled in the Centers
      for Disease Control and Prevention National Breast and Cervical Cancer Early
      Detection Program. Women were grouped according to age at the final Program Pap
      test (aged < 30, 30-44, 45-59, and 60-65 years) and by screening history (0, 1,
      2, and 3+ consecutive prior normal Program tests) to estimate cost per life-year
      and quality-adjusted life-year associated with annual, biennial, and triennial
      screening. RESULTS: For women aged 30-44 years with no prior tests, incremental
      cost-effectiveness ratios ranged from 20,533 US dollars for screening triennially
      (compared with no further screening) to 331,837 US dollars for screening annually
      (compared with biennially) per life-year saved. Among same-aged women with 3 or
      more prior normal Program tests, incremental cost-effectiveness ratios for the
      same measures ranged from 60,029 US dollars to 709,067 US dollars per life-year
      saved. Inclusion of the most conservative utility estimates resulted in
      incremental cost-effectiveness ratios in excess of 100,000 US dollars per quality
      adjusted life-year saved associated with annual screening of same-aged women with
      3 or more prior normal tests compared with biennial screening. CONCLUSION: As the
      number of prior normal Pap tests increases, the costs per life-year saved
      increase substantially. Resources should be prioritized for screening those never
      or rarely screened women. LEVEL OF EVIDENCE: II-2.

PMID- 16449120
TI  - Improved survival of Asians with corpus cancer compared with whites: an analysis
      of underlying factors.
AB  - OBJECTIVE: To compare the clinicopathologic prognosticators and survival of
      Asians and whites with corpus cancer. METHODS: Demographic, clinicopathologic,
      and survival data were obtained from the 1992-2001 Surveillance, Epidemiology,
      and End Results Program. Statistical analyses were performed by Kaplan-Meier
      methods and Cox proportional hazards model. RESULTS: A total of 2,144 Asians and
      32,999 whites with corpus cancer were identified. The age-adjusted incidence of
      uterine cancer in Asians compared with whites was 16.8 compared with 26.1 per
      100,000. Asians presented at a younger age (mean 58.4 years compared with 65.1; P
      < .01) and with more advanced stage disease than whites (21.5% compared with
      15.4%; P < .01). The 5-year survival rate for Asians was 79.4% compared with
      75.2% for whites (P < .01). Asians with stage I-II and III-IV cancers had 5-year
      survival rates of 89.3% and 41.2% compared with 82.3% and 34.0% for the whites,
      respectively (P < .01, early stage; P < .01, advanced stage). The survival
      advantage of Asians persists in endometrioid (P < .01) and uterine papillary
      serous carcinomas (P < .01), but not in clear cell carcinoma (P = .62) or
      sarcomas (P = .78). In multivariate analysis, younger age (P < .01), earlier
      stage (P < .01), favorable histology (P < .01), and lower grade (P < .01)
      remained as significant independent prognosticators for improved survival.
      However, race was not an important prognosticator. CONCLUSION: The overall
      survival advantage experienced by Asians with uterine cancer is attributable to
      their younger age at diagnosis. Because Asian women present at a younger age with
      more advanced disease, physicians should have an increased index of suspicion for
      malignancy in young Asian women with suspicious symptoms and consider a lower age
      threshold for biopsy in this group. LEVEL OF EVIDENCE: II-2.

PMID- 16449121
TI  - Subclinical hyperthyroidism and pregnancy outcomes.
AB  - OBJECTIVE: Subclinical hyperthyroidism has long-term sequelae that include
      osteoporosis, cardiovascular morbidity, and progression to overt thyrotoxicosis
      or thyroid failure. The objective of this study was to evaluate pregnancy
      outcomes in women with suppressed thyroid-stimulating hormone (TSH) and normal
      free thyroxine (fT(4)) levels. METHODS: All women who presented to Parkland
      Hospital for prenatal care between November 1, 2000, and April 14, 2003,
      underwent thyroid screening by chemiluminescent TSH assay. Women with TSH values
      at or below the 2.5th percentile for gestational age and whose serum fT(4) levels
      were 1.75 ng/dL or less were identified to have subclinical hyperthyroidism.
      Those women screened and delivered of a singleton infant weighing 500 g or more
      were analyzed. Pregnancy outcomes in women identified with subclinical
      hyperthyroidism were compared with those in women whose TSH values were between
      the 5th and 95th percentiles. RESULTS: A total of 25,765 women underwent thyroid
      screening and were delivered of singleton infants. Of these, 433 (1.7%) were
      considered to have subclinical hyperthyroidism, which occurred more frequently in
      African-American and/or parous women. Pregnancies in women with subclinical
      hyperthyroidism were less likely to be complicated by hypertension (adjusted odds
      ratio 0.66, 95% confidence interval 0.44-0.98). All other pregnancy complications
      and perinatal morbidity or mortality were not increased in women with subclinical
      hyperthyroidism. CONCLUSION: Subclinical hyperthyroidism is not associated with
      adverse pregnancy outcomes. Our results indicate that identification of
      subclinical hyperthyroidism and treatment during pregnancy is unwarranted. LEVEL
      OF EVIDENCE: II-2.

PMID- 16449122
TI  - Universal perinatal depression screening in an Academic Medical Center.
AB  - OBJECTIVE: To develop a department-based program to identify and treat women at
      risk for perinatal depression. METHODS: Private and employed physician groups
      were engaged to conduct antepartum maternal depression screening using the
      Edinburgh Postnatal Depression Scale. A comprehensive program was established to
      ensure that patients identified as being at risk would receive appropriate care.
      The program 1) developed a network of existing community mental health providers
      to accommodate screen-positive referrals, 2) created a 24/7 hotline staffed by
      mental health workers to respond to urgent/emergent patient needs, 3) provided
      nursing and physician education via a comprehensive curriculum on perinatal
      depression, and 4) facilitated outpatient depression screening that included a
      centralized scoring and referral system. RESULTS: A total of 4,322 women
      completed 4,558 screens during the initial 24 months (June 2003-May 2005).
      Although initial uptake of the screening program was gradual, all 20 departmental
      obstetric practices were screening their patients at the end of the first year.
      Depression screening was accomplished between 28-32 weeks of gestation, and
      postpartum screening (during the 6-week postpartum visit) was subsequently added.
      Overall, 11.1% of women screened positive in the antenatal period, and 7.3%
      screened positive in the postnatal period. Three hundred three women were
      referred for evaluation and care. CONCLUSION: Department-based, perinatal
      depression screening was feasible when individual physician practices were not
      required to develop the infrastructure necessary to respond to at-risk patients.
      We believe that the provision of clinical safety nets (mental health provider
      network and the hotline) were essential to the universal acceptance of this
      program by practitioners. LEVEL OF EVIDENCE: III.

PMID- 16449123
TI  - Women's views of prenatal violence screening: acceptability and confidentiality
      issues.
AB  - OBJECTIVE: The purpose of this research was to address the need for evidenced
      based practices for violence screening by identifying women's perceptions of, and
      experiences with, prenatal violence screening. METHODS: Audio- and video-enhanced
      anonymous computer interviews were completed by women in 2 Level III postpartum
      units. RESULTS: The sample was composed of 519 primarily African-American and
      white women who were educationally and economically diverse. Although 312 women
      (60.1%) reported being screened for violence by a health care provider at some
      point during their pregnancy, only 201 of 519 (38.7%) were asked by their
      prenatal care provider, with the remaining women reporting that they were
      screened during emergency room, triage visits, and labor and delivery admission.
      Of those who were screened by their prenatal care provider 195 of 201 (97%) women
      stated that they were not embarrassed, angry, or offended when assessed. Of the
      66 women who were both abused and screened during their pregnancy, only 11 women
      disclosed abuse, with a resulting disclosure rate of 16.7%; however, 29 abused
      women who denied abuse to their health care provider stated that they would have
      changed their response if they had known that violence disclosure was not
      reportable in their state unless the victim was seriously injured or was wounded
      with a lethal weapon. CONCLUSION: This study provides evidence that the great
      majority of pregnant women are not offended when screened for domestic violence
      and may increase their disclosure if they are told about state reporting mandates
      that preclude mandatory reporting for adults. LEVEL OF EVIDENCE: II-3.

PMID- 16449124
TI  - Beer consumption among hazardous drinkers during pregnancy.
AB  - OBJECTIVE: The objective of this study was to examine the prevalence of beer
      consumption among hazardous drinkers in our pregnant patient population. METHODS:
      This prospective clinic-based cohort study involved women who were surveyed
      during their first prenatal visit. Hazardous drinking was identified on alcohol
      surveys as frequent or binge drinking habits with related consequences.
      Participants completed initial and postpartum interviews about the quantity,
      frequency, and type (beer, wine, liquor, and/or combinations) of alcoholic
      beverages consumed before and after pregnancy recognition. RESULTS: Of the total
      4,494 patients who completed the survey, 203 (4.52%) met criteria for hazardous
      drinking, met study eligibility criteria, and completed the interviews. Beer was
      consumed most often (n = 151, 74.4%) and in greater quantities than wine (P <
      .05) or liquor (P < .01). Beer continued to be consumed by 52.3% women after
      pregnancy recognition. Although abstinence for prolonged periods was common
      during pregnancy, beer was consumed more than wine and liquor per drinking
      episode (2.7 versus 0.9 drinking units per drinking day; P = .002) indicating a
      binging pattern. Very few switched to drinking either a light beer (n = 6) or a
      nonalcoholic beer (n = 1). CONCLUSION: Beer is the most consumed among women with
      hazardous drinking habits before and after pregnancy awareness. Focusing on binge
      beer drinking is worthwhile during routine prenatal questioning. LEVEL OF
      EVIDENCE: II-2.

PMID- 16449125
TI  - Textbook recommendations for preventing and treating perineal injury at vaginal
      delivery.
AB  - OBJECTIVE: To assess general obstetrics textbooks regarding the quality and
      quantity of information about perineal injury at vaginal delivery. METHODS: An
      obstetrics and gynecology resident, a perinatologist, and a urogynecologist
      evaluated 7 obstetrics textbooks by using a standardized abstraction form that
      delineated descriptions of anatomy and physiology, episiotomy use, and perineal
      trauma prevention and repair. RESULTS: Two textbooks briefly described anal
      sphincter anatomy, but none provided a detailed discussion of the relative
      contribution of anatomic components to continence. Four textbooks discussed the
      evidence for and against midline or mediolateral episiotomy, and 6 advised
      against routine episiotomy. Six textbooks described grading lacerations, but only
      one described detailed repair techniques for all grades. Two textbooks discussed
      techniques to reduce perineal trauma at the time of delivery. Only one textbook
      discussed the need to reapproximate the normal anal sphincter anatomy during
      perineal repair. CONCLUSION: Although most textbooks accurately reflect current
      literature regarding routine episiotomy, there is limited discussion of
      advantages and disadvantages of various types of episiotomy and little offered
      regarding prevention and repair of perineal trauma at delivery. LEVEL OF
      EVIDENCE: III.

PMID- 16449126
TI  - Comparing three screening strategies for combining first- and second-trimester
      Down syndrome markers.
AB  - OBJECTIVE: To describe the choices and tradeoffs inherent in 3 published
      strategies that combine first- and second-trimester markers for Down syndrome
      screening. METHODS: Published marker distributions for Down syndrome and
      unaffected pregnancies in the first and second trimesters were combined with a
      maternal age distribution and age-associated Down syndrome risk in a statistical
      model to compare sequential, contingent, and integrated screening. RESULTS:
      Sequential and contingent screening strategies are always less efficient (higher
      false-positive rate for a given detection rate) than integrated screening, but
      the reduction in efficiency is dependent on the combination of risk cutoffs
      chosen. At a fixed false-positive rate, sequential and contingent strategies
      perform better when a higher proportion of the false positives occur in the
      second trimester. For all 3 strategies, increasing the overall false-positive
      rate from 2% to 5% increases detection (from approximately 85% to 91%). Although
      associated with reduced screening efficiency compared with integrated screening,
      both sequential and contingent screening identify the majority of detected Down
      syndrome cases early. With contingent screening, the process is also completed in
      the first trimester for most women. CONCLUSION: Integrated screening is the most
      efficient of the 3 strategies, but it is possible to select risk cutoffs for both
      sequential and contingent strategies that minimize losses in efficiency while
      maintaining early detection and early completion. For all of these strategies,
      well-designed intervention trials are needed to determine acceptability to women
      and providers in primary care settings and to assess real-world performance.
      LEVEL OF EVIDENCE: III.

PMID- 16449127
TI  - Obstetric outcomes in women with sonographically identified uterine leiomyomata.
AB  - OBJECTIVE: To examine the association between leiomyomata and complications
      during pregnancy, delivery, and the puerperium. METHODS: We conducted a
      retrospective cohort study comparing pregnancy outcomes in women with and without
      uterine leiomyomata who underwent routine second trimester obstetric
      ultrasonography and delivered viable infants at a single institution. Potential
      confounding variables, including maternal age, weight, ethnicity, parity,
      gestational age, epidural use, and labor induction, were controlled for using
      multivariate logistic regression techniques. RESULTS: From 1993 to 2003, 15,104
      women underwent routine second trimester prenatal ultrasonography, and 401 (2.7%)
      women were identified with at least 1 leiomyoma. By univariate and multivariate
      analyses, the presence of leiomyomata was associated with increased risks for
      cesarean delivery (adjusted odds ratio [AOR] 1.57, 95% confidence interval [CI]
      1.16-2.13), breech presentation (AOR 1.64, 95% CI 1.11-2.40), malposition (AOR
      1.59, 95% CI 1.18-2.15), preterm delivery (AOR 1.45, 95% CI 1.08-1.96), placenta
      previa (AOR 1.86, 95% CI 1.02-3.39), and severe postpartum hemorrhage (AOR 2.57,
      95% CI 1.54-4.27). Premature rupture of membranes, operative vaginal delivery,
      chorioamnionitis, and endomyometritis were not associated with leiomyomata.
      Median length of labor was not different between the 2 groups. When compared with
      leiomyomata less than 10 cm in size, leiomyomata 10 cm or larger were associated
      with rates of cesarean delivery that were not statistically different (25%
      compared with 31%, P = .49). CONCLUSION: Pregnant women with leiomyomata are at
      increased risk for cesarean delivery, breech presentation, malposition, preterm
      delivery, placenta previa, and severe post partum hemorrhage. Women with
      leiomyomata 10 cm or larger achieve a vaginal delivery rate of nearly 70%. These
      results are useful for preconception and prenatal counseling of women with
      leiomyomata. LEVEL OF EVIDENCE: II-2.

PMID- 16449128
TI  - Risk of stillbirth following a cesarean delivery: black-white disparity.
AB  - OBJECTIVE: We examine the association between prior cesarean delivery and risk of
      stillbirth in a subsequent pregnancy. METHODS: The Missouri maternally linked
      cohort data set containing births from 1978 through 1997 was used. We identified
      a cohort of women who delivered live births by cesarean delivery and a comparison
      cohort of women who delivered live births vaginally in their first pregnancies.
      We then compared the risks of stillbirth in the second pregnancy between the 2
      groups. RESULTS: We analyzed 396,441 women with information on first and second
      pregnancies, comprising 71,950 (18.1%) in the cesarean arm, and 324,491 (81.9%)
      in the vaginal birth arm. Rates of stillbirth among women with and those without
      history of cesarean delivery were 4.4 and 4.1 per 1,000 births, respectively (P =
      .2). The adjusted estimates also showed no difference in risk for stillbirth
      between the 2 groups (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.0-1.3).
      Among whites, the stillbirth rates in women with and those without history of
      cesarean delivery were 3.7 and 3.6 per 1,000 births, respectively (OR 1.0, 95% CI
      0.9-1.2). Among blacks, both the absolute and the adjusted relative risks for
      stillbirth were elevated in mothers with history of cesarean delivery (stillbirth
      rate 9.3 versus 6.8 per 1,000 births; OR 1.4, 95% CI 1.1-1.7). CONCLUSION:
      Overall, our analysis did not detect an association between cesarean history and
      subsequent stillbirth. However, cesarean delivery may increase the risk for
      subsequent stillbirth among black mothers, a group with the highest cesarean
      delivery rate in the country. LEVEL OF EVIDENCE: III.

PMID- 16449129
TI  - Is race a determinant of stillbirth recurrence?
AB  - BACKGROUND: A history of stillbirth may result in an increased risk for
      recurrence, although information regarding this remains scanty. It is also
      uncertain whether race is a determinant of stillbirth recurrence given that the
      risk of stillbirth varies across racial and ethnic populations. METHODS: The
      Missouri maternally linked cohort data set containing births from 1978 through
      1997 was used. We identified the study group (women who experienced a stillbirth
      in the first pregnancy) and a comparison group (women who delivered a live birth
      in their first pregnancy) and compared the outcome (stillbirth) in the second
      pregnancy between the 2 groups. RESULTS: We analyzed 404,180 women with
      information on first and second pregnancies (1,979 [0.5%] in the study arm, and
      402,201 [99.5%] in the comparison arm). Of the 1,929 cases of stillbirths in the
      second pregnancy, 45 cases occurred in mothers with a history of stillbirth
      (stillbirth rate = 22.7/1000) and 1,884 in the comparison group (stillbirth rate
      4.7/1,000, P < .001). The adjusted risk of stillbirth was almost 5-fold as high
      in women with a prior stillbirth (odds ratio 4.7, 95% confidence interval 3.3
      6.6). Analysis across racial groups revealed that whites had lower absolute risk
      for stillbirth recurrence than African Americans (19.1/1,000 compared with
      35.9/1,000, P < .05). The elevated stillbirth recurrence risk was confirmed after
      adjusting for potential confounders (odds ratio 2.6, 95% confidence interval 1.2
      5.7). CONCLUSION: History of stillbirth is associated with a 5-fold increase for
      subsequent stillbirth. The recurrence of stillbirth is almost tripled in African
      Americans as compared with whites. LEVEL OF EVIDENCE: II-2.

PMID- 16449131
TI  - Primary amenorrhea in a teenager.

PMID- 16449130
TI  - Suspected ectopic pregnancy.
AB  - Women who present with pain and bleeding in the first trimester are at risk for
      ectopic pregnancy, a life-threatening condition. Conditions that predispose a
      woman to ectopic pregnancy are damaged fallopian tubes from prior tubal surgery
      or previous pelvic infection, smoking, and conception using assisted
      reproduction. Many women without risk factors can develop an ectopic pregnancy. A
      diagnostic algorithm that includes the use of transvaginal ultrasonography, human
      chorionic gonadotropin (hCG) concentrations, and, sometimes, uterine curettage
      can definitively diagnose women at risk in a timely manner. The absence of an
      intrauterine pregnancy above an established cut point of hCG is consistent with
      an abnormal pregnancy but does not distinguish a miscarriage from an ectopic
      pregnancy. When the initial hCG value is low, serial hCG values can be used to
      determine whether a gestation is potentially viable or spontaneously resolving.
      The minimal rise in hCG for a viable pregnancy is 53% in 2 days. The minimal
      decline of a spontaneous abortion is 21-35% in 2 days, depending on the initial
      level. A rise or fall in serial hCG values that is slower than this is suggestive
      of an ectopic pregnancy. Women diagnosed with an unruptured ectopic pregnancy are
      potential candidates for medical management with methotrexate. Intramuscular
      injection with methotrexate can be used to safely treat an ectopic pregnancy with
      success rates, tubal patency rates, and future fertility that are similar to
      those obtained with conservative surgery. Success rates using methotrexate are
      inversely rated to baseline hCG values and are higher using "multidose" compared
      with "single-dose" regimens. Surgical treatment may be conservative or definitive
      and should be attempted in most cases via laparoscopy.

PMID- 16449132
TI  - Severe mesh complications following intravaginal slingplasty.

PMID- 16449133
TI  - Severe mesh complications following intravaginal slingplasty.

PMID- 16449134
TI  - First-trimester septated cystic hygroma: prevalence, natural history, and
      pediatric outcome.

PMID- 16449135
TI  - Genital herpes complicating pregnancy.

PMID- 16449136
TI  - Forceps compared with vacuum: rates of neonatal and maternal morbidity.

PMID- 16449137
TI  - Management of interstitial pregnancy using selective uterine artery embolization.

PMID- 16449138
TI  - ACOG Committee Opinion #328: patient safety in the surgical environment.
AB  - Ensuring patient safety in the operating room begins before the patient enters
      the operative suite and includes attention to all applicable types of preventable
      medical errors (including, for example, medication errors), but surgical errors
      are unique to this environment. Steps to prevent wrong-site, wrong-person, or
      wrong-procedure errors have been recommended. Prevention of surgical errors
      requires the attention of all personnel involved in the patient's care.

PMID- 16449139
TI  - The dangers of complacency.

PMID- 16449140
TI  - Cerebral vasculopathies masquerading as eclampsia.

PMID- 16449141
TI  - A cautionary tale: fatal outcome of methotrexate therapy given for management of
      ectopic pregnancy.
AB  - BACKGROUND: Medical therapy with methotrexate is a standard practice for the
      commonly encountered problem of ectopic pregnancy. Methotrexate is excreted
      predominantly by the kidney and should be used with extreme caution in renal
      insufficiency. All physicians who administer methotrexate must understand its
      mechanism of action, distribution, and elimination to minimize potential risks to
      the patient. CASE: A young, dialysis-dependent woman received a standard dose of
      methotrexate for an ectopic pregnancy. Prolonged methotrexate exposure resulted.
      The consequences-pancytopenia, desquamation, acute respiratory distress syndrome,
      and profound bowel ischemia-ultimately led to her death. CONCLUSION:
      Methotrexate, even at extremely low doses, can be fatal in patients with renal
      insufficiency. Alternative means of therapy should be sought for women with
      ectopic pregnancy and renal failure.

PMID- 16449143
TI  - Call-Fleming postpartum angiopathy in the puerperium: a reversible cerebral
      vasoconstriction syndrome.
AB  - BACKGROUND: The postpartum angiopathy (Call-Fleming syndrome) is a rare,
      reversible cerebral vasoconstriction syndrome. Unlike in eclampsia, neither
      proteinuria nor hypertension have been observed in the Call-Fleming syndrome.
      CASE: A 17-year-old woman developed headache, seizures, confusion, cortical
      blindness, and denial of visual loss (optic anosognosia, Anton syndrome) on the
      first postpartum day. Transcranial Doppler demonstrated severely elevated blood
      velocities. Magnetic resonance angiography showed multifocal segmental narrowing
      of cerebral arteries. Magnetic resonance imaging revealed occipitotemporal edema.
      After symptomatic treatment, the clinical deficits disappeared completely within
      2 weeks. The follow-up neuroimaging performed after 3 months was unremarkable.
      CONCLUSION: The case shows that the Call-Fleming syndrome is a reversible
      condition with excellent prognosis representing an important differential
      diagnosis of eclampsia, dural sinus thrombosis, and intracranial bleeding in
      puerperium.

PMID- 16449142
TI  - Postpartum eclampsia complicated by reversible cerebral herniation.
AB  - BACKGROUND: Preeclampsia and eclampsia have been associated with significant
      morbidity and mortality. Posterior reversible encephalopathy syndrome is a
      neuroradiologic entity that has been previously reported to occur in patients
      with preeclampsia and eclampsia. We present, to our knowledge, the first reported
      case of late postpartum eclampsia complicated by posterior reversible
      encephalopathy syndrome and reversible cerebral herniation. CASE: A 39-year-old
      woman (para 1) presented with late postpartum preeclampsia on postpartum day 4.
      She developed eclampsia and posterior reversible encephalopathy syndrome, which
      was diagnosed by magnetic resonance imaging. She subsequently developed clinical
      and radiologic evidence of reversible cerebral herniation. CONCLUSION: Postpartum
      preeclampsia and eclampsia that is complicated by posterior reversible
      encephalopathy syndrome can result in cerebral herniation. Neuroradiologic
      imaging may be a useful adjunctive diagnostic tool in the setting of preeclampsia
      and eclampsia to predict disease severity.

PMID- 16449145
TI  - Colouterine fistula secondary to endometriosis with associated chorioamnionitis.
AB  - BACKGROUND: Intestinal endometriosis may be complicated by bowel obstruction,
      colonic rupture, sepsis, and rarely, malignant transformation. Fistula formation
      is extremely rare. CASE: A 26-year-old woman presented at 16 weeks of gestation
      with an acute abdomen suggestive of ruptured appendicitis. Blood cultures were
      positive for Bacteroides fragilis. At laparotomy, she was found to have a
      colouterine fistula with pelvic sepsis. The resected specimens demonstrated
      extensive uterine adenomyosis and endometriosis of the cecum, with a fistulous
      tract lined by endometriosis and suppurative inflammation extending from the
      cecum to the uterine endometrial cavity associated with severe chorioamnionitis
      and endomyometritis. CONCLUSION: This case illustrates a rare complication of
      colouterine fistula secondary to intestinal endometriosis.

PMID- 16449146
TI  - Breastfeeding during tacrolimus therapy.
AB  - BACKGROUND: Solid organ transplant recipients are usually advised against
      breastfeeding because of the questionable safety of immunosuppressants. Limited
      data suggest that infant exposure to tacrolimus via milk is low. This report
      characterizes the milk-to-blood ratio for tacrolimus using area under the
      concentration-time curve analysis in a renal transplant patient. CASE: A 29-year
      old woman was exclusively breastfeeding her healthy 3-month-old infant while on
      tacrolimus 4 mg daily plus other drugs relevant to her transplant. The milk-to
      blood ratio was 0.23, and average tacrolimus concentrations in milk were 1.8
      microg/L. The baby ingested approximately 0.5% of the maternal dose (weight
      adjusted). CONCLUSION: Infant exposure to tacrolimus in milk is very low,
      suggesting that maternal tacrolimus therapy may be compatible with breastfeeding.

PMID- 16449144
TI  - Spontaneous intrapartum vesicouterine fistula.
AB  - BACKGROUND: Vesicouterine fistulae as an obstetrical complication have been
      reported only in women with a history of cesarean. We present a patient with no
      such history who developed a vesicouterine fistula after vaginal delivery. CASE:
      A 43-year-old gravida 5 at term with no history of cesarean presented in the
      latent phase of labor. Gross hematuria was noted intrapartum, and a foley
      catheter was placed. A cystogram showed an extraperitoneal bladder perforation.
      The patient had urinary incontinence despite Foley catheter drainage. The
      diagnosis of vesicouterine fistula was made by cystoscopy and fistulogram. The
      patient had a successful repair at 3 months. CONCLUSION: This is a rare case of a
      vesicouterine fistula developing during a pregnancy with no previous cesarean.
      Accurate diagnosis is essential because surgical repair has an excellent outcome.

PMID- 16449147
TI  - Pregnancy exacerbating hepatopulmonary syndrome.
AB  - BACKGROUND: Hepatopulmonary syndrome is an uncommon complication of liver
      cirrhosis. The natural history of this condition and its optimal management
      during pregnancy are not yet known. CASE: We present the case of a 35-year-old
      woman with liver cirrhosis who developed severe dyspnea in the 25th week of
      gestation and was diagnosed as suffering from hepatopulmonary syndrome. She was
      managed conservatively until 35 weeks of gestation, when she was delivered by
      cesarean. CONCLUSION: The natural history, in this case, indicates that pregnancy
      may induce hepatopulmonary syndrome in an otherwise asymptomatic cirrhotic
      patient. Oxygen supplementation was the cornerstone of treatment and resulted in
      a favorable outcome.

PMID- 16449148
TI  - Fetal death in a patient with intrahepatic cholestasis of pregnancy.
AB  - BACKGROUND: Treatment with ursodeoxycholic acid in intrahepatic cholestasis of
      pregnancy reduces concentration of transaminases and bile acids in maternal
      serum, and is thought to reduce fetal death. We report a case of fetal death in a
      patient with intrahepatic cholestasis of pregnancy who had responded well to
      ursodeoxycholic acid, demonstrated by a low bile level. CASE: A young nulliparous
      woman presented with intrahepatic cholestasis of pregnancy at 28 weeks of
      gestation. Transaminases and bile acids decreased after ursodeoxycholic acid
      administration. The patient was discharged from the hospital until delivery and
      received biochemical markers and conventional fetal monitoring twice weekly. Due
      to low bile acid values (< 13 UI/L) and unfavorable cervix, the patient was
      followed up expectantly. Fetal death occurred at 39 weeks and 3 days, although
      cardiotocograph testing results were normal the day before. CONCLUSION: When lung
      maturity is achieved for patients with intrahepatic cholestasis of pregnancy,
      delivery should be considered.

PMID- 16449149
TI  - Necrotizing fasciitis of the scalp in a newborn.
AB  - BACKGROUND: Fetal scalp electrode monitoring is usually without complications,
      but on rare occasions it can serve as a portal of entry for organisms colonizing
      the maternal genital tract. CASE: We present a case of neonatal necrotizing
      fasciitis of the scalp that was associated with intrapartum fetal scalp electrode
      monitoring. Skin cultures grew Group A Streptococcus M11 T nontypeable serotype,
      an unusual cause of neonatal necrotizing fasciitis. The neonate's mother had a
      concurrent perineal infection and the same Group A streptococcal serotype was
      cultured from maternal blood and vaginal swabs. CONCLUSION: This case highlights
      the emergence of life-threatening Group A Streptococcus causing invasive disease
      in both infants and mothers and the need for careful monitoring of neonates who
      have had intrapartum electrode monitoring.

PMID- 16449150
TI  - Diagnosis of placental abscess in association with recurrent maternal bacteremia
      in a twin pregnancy.
AB  - BACKGROUND: Placental abscess formation is rarely recognized prenatally. We
      present a case detected ultrasonographically that developed from a central line
      infection and caused recurrent maternal bacteremia. CASE: A young woman with a 21
      week twin gestation presented with recurrent fevers. She had received treatment
      for bacteremia due to Serratia marcescens. The initial source of the infection
      was a peripherally inserted central catheter line placed in the first trimester
      for hyperemesis gravidarum. Fevers continued throughout the second course of
      antibiotics. An abscess seen sonographically in twin A's placenta was aspirated
      using a spinal needle, revealing Serratia bacteria. Aspiration was performed at
      22 weeks of gestation. Amniotic fluid samples obtained from both sacs were
      negative for infection. Over 4 weeks, the abscess enlarged and she was delivered.
      Twin A died of sepsis and twin B had a relatively favorable neonatal course.
      CONCLUSION: Prenatal diagnosis of placental abscess presents a difficult
      management dilemma. Traditional amniotic fluid studies did not predict the poor
      outcome of the affected fetus.

PMID- 16449151
TI  - Torsion of the appendix mimicking ovarian torsion.
AB  - BACKGROUND: Appendiceal torsion is rare and generally seen more frequently in
      children than adults. Untreated it can lead to necrosis, ulceration, and
      subsequent peritonitis. CASE: A middle-aged female presented with a 5-day history
      of cramping abdominal pain and nausea and vomiting. Abdominal wall guarding and
      rebound tenderness was noted on examination. Computerized tomography showed an 8
      x 4 cm mass anterior to the uterus, suggestive of degenerating fibroid versus
      ovarian dermoid cyst. Laparoscopy was performed for presumed ovarian torsion.
      Torsion of the appendix was discovered and treated by laparoscopic appendectomy.
      CONCLUSION: Patients with presumed ovarian torsion should undergo urgent
      laparoscopy for diagnosis and attempted ovarian salvage. The possibility of
      conditions that may require different surgical interventions, such as appendiceal
      torsion, should be considered.

PMID- 16449152
TI  - Acute abdominal pain as the presenting symptom of isolated iliac vein thrombosis
      in pregnancy.
AB  - BACKGROUND: The incidence of iliac vein thrombosis in pregnancy is quite low;
      however when it does occur, delay in diagnosis can have significant sequelae. We
      report a pregnant woman who presented with severe acute abdominal pain secondary
      to isolated iliac vein thrombosis. CASE: A primigravida presented at 33 weeks of
      gestation with acute onset of severe left-sided lower abdominal pain. A magnetic
      resonance imaging study revealed isolated left iliac vein thrombosis. After
      treatment with heparin her pain completely resolved. CONCLUSION: Iliac vein
      thrombosis may cause acute abdominal pain in pregnant women and should be
      considered in the differential diagnosis when other common causes of pain have
      been excluded.

PMID- 16449153
TI  - Inadvertent vesicular placement of a vaginal contraceptive ring presenting as
      persistent cystitis.
AB  - BACKGROUND: The NuvaRing is a soft, flexible, ring-shaped vaginal contraceptive
      device that is placed by the user herself. Incorrect placement has not been
      described, because any intravaginal position allows appropriate hormonal delivery
      through the vaginal mucosa. CASE: A 22-year-old otherwise healthy woman presented
      with 2 months of urinary urgency, frequency, and pelvic pain, which were
      unresponsive to antibiotic therapy. Her symptoms began immediately after
      placement of a NuvaRing vaginal contraceptive device, which she was subsequently
      unable to locate. Thorough evaluation revealed the ring in the urinary bladder.
      CONCLUSION: Bladder or urethral foreign body should be considered in the
      evaluation of patients with chronic cystitis, especially if the patient uses
      vaginal medical devices. Intravesicular placement of a device may occur even
      without psychiatric or physical comorbidities.

PMID- 16449154
TI  - Five cases of tape erosion after transobturator surgery for urinary incontinence.
AB  - BACKGROUND: Before introducing the transobturator tape into our practice we
      undertook 52 transobturator tape procedures. The transobturator tape procedures
      were undertaken with an "outside-in" approach, using nonwoven polypropylene mesh
      with average pore size of 50 mum. CASES: Five cases of vaginal erosions have been
      identified, 1 complicated by a groin abscess. All cases required further
      procedures to trim (n = 3), resect (n = 1) or remove (n = 1) the tape. One woman
      had a tension-free vaginal tape procedure. To date, 3 women remain incontinent.
      CONCLUSION: Possible reasons for the complications include 1) surgical
      inexperience (unlikely, given that we have undertaken more than 2000 tension-free
      vaginal tape procedures without similar complication rates); 2) inherent
      susceptibility of the "hammock" position of the transobturator tape; or 3) the
      nonwoven polypropylene tape with mesh size of 50 microm itself may predispose to
      erosion or abscess.

PMID- 16449155
TI  - Osteomyelitis secondary to sacral colpopexy mesh erosion requiring laminectomy.
AB  - BACKGROUND: Severe infectious morbidity associated with the use of synthetic mesh
      and abdominal sacral colpopexy is rare. Pelvic abscess, sinus tract formation,
      enterovaginal fistula, and osteomyelitis have been reported. CASE: This case
      involves a patient who presented with staphylococcal bacteremia and vaginal
      erosion of a sacral colpopexy synthetic mesh. Despite prolonged courses of
      intravenous antibiotics and complete removal of the mesh material, she developed
      osteomyelitis. Progressive neurologic symptoms required a decompression
      laminectomy to facilitate a complete recovery and resolution of symptoms.
      CONCLUSION: In the treatment of abdominal sacral colpopexy mesh erosion, we
      recommend maintaining a high index of suspicion for secondary infections.

PMID- 16449156
TI  - Osteomyelitis of the pubic symphysis in pregnancy.
AB  - BACKGROUND: Pubic symphysis osteomyelitis during the antepartum period of
      pregnancy is rare. CASE: We report a patient in the third trimester who presented
      with pubic pain, low-grade fever, and altered gait. She was found to have a
      retropubic abscess at the time of cesarean delivery. Radiologic imaging showed
      findings consistent with osteomyelitis of the pubic symphysis and multiple pus
      collections in the pelvis and labia. The patient was treated with surgical
      debridement of the affected bone and placement of antibiotic-impregnated beads.
      CONCLUSION: Osteomyelitis of the pubic symphysis can have serious complications.
      The diagnosis should be considered in pregnant patients with clinical findings
      unusual for pubic symphysis diastases. It can be treated with antibiotic
      impregnated beads.

PMID- 16449157
TI  - Nausea, emesis, and muscle weakness in a pregnant adolescent.
AB  - BACKGROUND: Gitelman syndrome is a rare autosomal recessive disorder that
      presents in early adulthood with fatigue, muscle cramps and electrolyte
      abnormalities. CASE: A 17-year-old African-American woman presented at 17 weeks
      of pregnancy with nausea, emesis, profound lower extremity proximal muscle
      weakness, hypokalemia, and hypomagnesemia. After a thorough evaluation, Gitelman
      syndrome was diagnosed. The patient was maintained on high levels of potassium
      and magnesium supplementation throughout the rest of her pregnancy and delivered
      a healthy infant. CONCLUSION: In pregnancy, nausea and emesis is most commonly
      attributed to hyperemesis gravidarum. However, an atypical presentation of these
      symptoms and/or the coexistence of less common complaints warrant further
      investigation.

PMID- 16449158
TI  - Baking soda pica: a case of hypokalemic metabolic alkalosis and rhabdomyolysis in
      pregnancy.
AB  - BACKGROUND: We report a case of baking soda pica in a woman at 31 weeks of
      pregnancy causing severe hypokalemic metabolic alkalosis and rhabdomyolysis.
      CASE: A multigravida at 31 weeks of gestation presented with weakness and muscle
      pain. She was found to have severe hypokalemic metabolic alkalosis and
      rhabdomyolysis, with elevation in serum transaminases and hypertension. We
      initially thought the patient had an atypical presentation of preeclampsia until
      it was realized that she was ingesting 1 full box of baking soda (454 g sodium
      bicarbonate) per day. Symptoms and abnormal laboratory findings resolved with
      discontinuation of the patient's pica practices. CONCLUSION: Pica is a common but
      often overlooked practice that can potentially lead to life-threatening
      disorders. A thorough evaluation of a patient's dietary intake is extremely
      important, especially in the setting of atypical presentations of disease in
      pregnancy.

PMID- 16449159
TI  - Wernicke's encephalopathy with hyperemesis and ketoacidosis.
AB  - BACKGROUND: Avitaminosis can result from the acute malnutrition associated with
      prolonged pregnancy-related hyperemesis. Serious complications may arise from
      thiamine deficiency under these circumstances. CASE: We review the relevant
      literature and describe a case with central nervous system involvement presenting
      with typical manifestations of Wernicke's encephalopathy, apparently precipitated
      by a combination of hyperemesis gravidarum, diabetic ketoacidosis, and
      intravenous glucose administration. CONCLUSION: While this life-threatening
      complication is rare, it is important for all who care for obstetric patients to
      be aware of it and alert to its development. Early recognition is critical given
      the need to treat affected women expeditiously to help avoid potentially fatal
      adverse consequences. Prophylactic thiamine supplementation should be considered
      in the care of gravidas with hyperemesis.

PMID- 16449160
TI  - Conservative management of a bleeding renal angiomyolipoma in pregnancy.
AB  - BACKGROUND: Bleeding angiomyolipomas in pregnancy are rare but may be devastating
      and potentially fatal. In previous cases, most of these lesions have been managed
      with urgent nephrectomy or embolization. Only one other case report describes
      treating these lesions through conservative management and vaginal delivery.
      CASE: A 32-year-old woman with known bilateral angiomyolipomas presented at 39
      weeks of gestation with acute onset left flank pain. The ultrasound result was
      consistent with a bleeding angiomyolipoma. The patient was otherwise
      hemodynamically stable and was managed safely in a conservative outpatient
      approach that consisted of close clinic follow-up, serial hemoglobins, ultrasound
      studies, and vaginal delivery. CONCLUSION: Bleeding angiomyolipomas in pregnancy
      were managed successfully through conservative management and vaginal delivery.

PMID- 16449161
TI  - Use of a fascial prosthesis for management of abdominal compartment syndrome
      secondary to obstetric hemorrhage.
AB  - BACKGROUND: Massive obstetric hemorrhage can be catastrophic, with considerable
      maternal morbidity and mortality. CASE: A 41-year-old term gravida experienced
      massive postpartum hemorrhage attributed to an amniotic fluid embolism with rapid
      development of disseminated intravascular coagulation and resultant abdominal
      compartment syndrome. In this critically ill patient, a fascial prosthesis used
      for abdominal wall closure was placed to expedite multiple abdominal explorations
      and packing. Additionally, this device facilitated fascial closure once the
      abdominal compartment syndrome was resolved. CONCLUSION: Abdominal compartment
      syndrome resulting from overwhelming obstetric hemorrhage may necessitate
      emergent decompressive laparotomy to alleviate increased intra-abdominal pressure
      and end-organ dysfunction. The fascial prosthesis allows a staged abdominal wall
      closure to be performed once the abdominal compartment syndrome is resolved.

PMID- 16449162
TI  - Post-loop electrosurgical excision procedure sepsis in a human immunodeficiency
      virus-infected woman.
AB  - BACKGROUND: Squamous intraepithelial lesions are more prevalent in women infected
      with the human immunodeficiency virus (HIV) compared with immunocompetent women.
      Loop electrosurgical excision procedure (LEEP) is commonly used to treat squamous
      intraepithelial lesions because it may be performed as an outpatient procedure
      with minimal blood loss and a low complication rate. CASE: We report a major
      infectious post-LEEP complication in an HIV-infected female who had an uneventful
      LEEP in which a cellulose hemostatic agent was used. Despite the severity of the
      infection, she was successfully treated with a minor surgical procedure along
      with broad antibiotic coverage. CONCLUSION: Although a cellulose hemostatic agent
      contaminated with perineal secretions may have served as a nidus for infection,
      use of perioperative antibiotics or cervical cleansing should be considered to
      prevent sepsis in immunocompromised hosts.

PMID- 16449163
TI  - Recurrent ascites due to oral contraceptives and pregnancy.
AB  - BACKGROUND: Ascites during pregnancy is a rare disorder with wide differential
      diagnosis. CASE: We report on 8 years of follow-up of a patient suffering from
      recurrent episodes of ascites following oral contraceptive use and during both
      her pregnancies. Each ascitic event resulted in spontaneous recovery. CONCLUSION:
      The mechanism underlying our patient's fluid shift remains an enigma. We
      hypothesize that during her pregnancy and when oral contraceptives were
      administered, high levels of endogenous or exogenous sex hormones led to
      increased permeability and fluid displacement.

PMID- 16449164
TI  - Pelvic organ myiasis.
AB  - BACKGROUND: Myiasis is infestation with dipterous larvae, which feed on the
      host's dead or living tissue, liquid body substances, or ingested food. CASE: A
      76-year-old, multiparous woman presented at a tertiary care hospital in India
      with vaginal discharge and itching for 3 weeks. The patient had a health care
      attendant who apparently failed to notice the problems she was experiencing.
      Pelvic examination revealed grade 2 uterine prolapse. Vaginal discharge was
      purulent, foul smelling, and contained several 8-10-mm white maggots of Musca
      domestica (housefly). Turpentine oil was instilled locally, and maggots were
      removed manually. The patient was treated with broad spectrum antibiotics. Maggot
      removal was repeated weekly for 3 weeks until no further maggots were present.
      Hysteroscopy was normal. The prolapsed uterus was replaced in its anatomic
      position with vaginal pessary. CONCLUSION: Decreased physical and mental
      capabilities due to old age and poor care by health providers can lead to maggot
      infestation of prolapsed pelvic organs.

PMID- 16449165
TI  - Paraneoplastic subacute sensory neuronopathy secondary to a malignant mixed
      mullerian tumor.
AB  - BACKGROUND: Paraneoplastic subacute sensory neuronopathy is a rapidly progressive
      autoimmune disorder commonly associated with small cell cancers. Relentless
      destruction of dorsal root ganglion cells by cytotoxic T cells leads to a poor
      prognosis. CASE: A 42-year-old woman developed sensory loss in both lower
      extremities 10 days after debulking of a uterine malignant mixed mullerian tumor.
      She progressed to sensory loss over the entire body, with initially preserved
      strength, severe dysmetria, and truncal ataxia. Her serum was positive for
      antineuronal nuclear antibody-1 (anti-Hu), confirming the diagnosis of
      paraneoplastic subacute sensory neuronopathy. Despite treatment with intravenous
      immunoglobulin, methylprednisolone, and plasmapheresis, she remained severely
      disabled. CONCLUSION: Because neuronal damage is irreversible, early recognition
      may be the only means to prevent severe neurologic disability.

PMID- 16449166
TI  - Risk of surgery after use of potassium chloride for treatment of tubal
      heterotopic pregnancy.
AB  - BACKGROUND: Spontaneous heterotopic pregnancies are rare, but with assisted
      reproductive techniques the incidence may approach 1:100. With the widespread use
      of transvaginal ultrasonography, physicians have attempted treatment of
      heterotopic pregnancies with minimally invasive procedures such as transvaginal
      guided potassium chloride (KCl) injection. However, there are few data on the
      success of this treatment. CASE: A 30-year-old primigravida presented with a
      desired pregnancy and was found to have a tubal pregnancy in addition to an
      intrauterine pregnancy. Ultrasound-guided KCl injection into the heterotopic
      pregnancy was complicated by abdominal pain, surgical abdomen, and hemoperitoneum
      requiring salpingectomy. CONCLUSION: A review of the literature revealed that 55%
      of tubal heterotopic pregnancies treated by KCl injection required subsequent
      salpingectomy. This raises concerns about the advisability of this treatment.

PMID- 16449167
TI  - Transvaginal local injection of hyperosmolar glucose for the treatment of
      heterotopic pregnancies.
AB  - BACKGROUND: We report the technique and long-term outcome after a conservative
      approach for the treatment of heterotopic pregnancy. CASE: Two women aged 31 and
      30 years presented with heterotopic pregnancies after controlled ovarian
      hyperstimulation intrauterine insemination. Transvaginal ultrasound-guided needle
      aspiration of the ectopic gestational sac and instillation of hyperosmolar
      glucose were performed. The ectopic pregnancies resolved without further
      intervention in both cases. The intrauterine pregnancies resulted in live births
      by cesarean delivery. Bilateral tubal patency was subsequently confirmed in both
      patients. CONCLUSION: Local injection of 50% glucose after aspiration of the
      tubal gestational sac fluid under transvaginal ultrasonographic guidance proved
      effective in resolving the ectopic pregnancy without adversely affecting the
      concurrent intrauterine pregnancy. This is a simple and inexpensive treatment
      modality.

PMID- 16449168
TI  - Extracorporeal membrane oxygenation therapy for circulatory arrest due to
      postpartum hemorrhage.
AB  - BACKGROUND: Cardiac arrest after postpartum hemorrhage may not respond to
      advanced life support. Various resuscitation methods have been proposed,
      including sternotomy and direct cardiac massage. Extracorporeal membrane
      oxygenation (ECMO) might be an alternative. CASE: We report the case of a woman
      who suffered atonic uterine hemorrhage perioperatively after cesarean delivery of
      twins. During initial conservative treatment using prostaglandin analog
      (sulprostone), cardiac decompensation developed and was followed by
      cardiopulmonary arrest. Circulatory failure remained unresponsive after 2 hours
      of resuscitation, when ECMO was initiated. The ensuing recovery was favorable.
      CONCLUSION: Aggressive mechanical circulatory support, such as ECMO, should be
      considered in a case of potentially reversible cardiocirculatory failure in a
      young obstetric patient.

PMID- 16449169
TI  - Use of a doula for labor coaching in a patient with indolent systemic
      mastocytosis in pregnancy.
AB  - BACKGROUND: Few cases of pregnancy in women with systemic mastocytosis have been
      reported. The effects of this disease on pregnancy have not been well documented,
      nor have the benefits of doula services for labor been reported for mastocytosis.
      CASE: A 35-year-old woman with indolent systemic mastocytosis sought
      preconception counseling regarding the effects of her disease on pregnancy and
      the effects of drugs and anesthesia on her disease. She then had an uncomplicated
      pregnancy and delivery, with multidisciplinary coordination and assistance by
      doulas to reduce the need for medication in labor. CONCLUSION: Mastocytosis
      patients can achieve normal pregnancy outcomes. Predelivery planning can help
      prepare staff and patients for complications. Doulas can assist with labor
      preparation and delivery using nonmedical approaches to relief of pain and
      anxiety.

PMID- 16449170
TI  - Alerting pregnant women to the risk of reptile-associated salmonellosis.
AB  - BACKGROUND: Reptile- and amphibian-associated salmonellosis poses significant
      risk to infants and young children. The Centers for Disease Control and
      Prevention has advised that reptiles and amphibians should not be kept in
      households with children younger than 5 years old. CASE: We report a 5-day-old
      newborn with Salmonella bacteremia and meningitis who survived but with severe
      developmental delay. CONCLUSION: Cases of infants with reptile- and amphibian
      associated salmonellosis, a preventable and devastating disease, continue to be
      reported. We propose that obstetricians should be the front line in counseling
      expecting families that reptiles should not be kept in households with infants
      and young children. By the time a family first visits the pediatrician, the
      warning may be too late.

PMID- 16449171
TI  - Ultrasonography-guided transvaginal endometrial biopsy: a useful technique in
      patients with cervical stenosis.
AB  - BACKGROUND: In patients with failed dilatation and curettage due to stenotic
      cervix, options for endometrial sampling are limited. We propose the
      ultrasonography-guided transvaginal endometrial biopsy. CASES: Two postmenopausal
      women presented with bleeding and failed dilatation and curettage due to a
      stenotic cervix. Under direct transvaginal ultrasound guidance, a 20-gauge needle
      was inserted through the vaginal vault and anterior uterine wall into the
      endometrium. The endometrium was aspirated, and specimen was submitted to
      cytology. One patient had endometrial adenocarcinoma and underwent a staging
      procedure. The other patient had a benign cytology and was followed up
      clinically. CONCLUSION: The ultrasonography-guided endometrial biopsy is a viable
      option for endometrial sampling in the presence of stenotic cervix.

PMID- 16449172
TI  - Urinary calculus associated with female genital cutting.
AB  - BACKGROUND: Female genital cutting is a cultural practice seen in parts of Africa
      and Asia. Women who have undergone type III female genital cutting (excising the
      external genitalia and suturing the remnant tissue to cover the urethra and part
      of the introitus) can suffer various long-term complications. Defibulation, a
      procedure that opens the overlying scar can alleviate or resolve symptoms. CASE:
      A 32-year-old Somali woman presenting with type III female genital cutting
      complained of infertility, dyspareunia, dysmenorrhea, and exquisite pain upon
      sitting. She underwent a defibulation procedure to create neolabia majora.
      Intraoperatively, a 0.8 cm urinary calculus was found beneath the urethra.
      Postoperatively, all of her symptoms resolved. CONCLUSION: Infibulated scars
      create a favorable environment for stagnant urine to crystallize and become a
      urinary calculus.

PMID- 16449173
TI  - A rare case of precoccygeal endometriosis.
AB  - BACKGROUND: Endometriosis is commonly identified in the abdomen, specifically the
      ovaries, adnexa, and fallopian tubes, and sometimes in more distant areas;
      precoccygeal endometriosis is an extremely rare phenomenon. CASE: We present a
      case involving a 44-year-old woman diagnosed and treated for precoccygeal
      endometriosis. She underwent laparotomy, extensive lysis of pelvic adhesions, and
      resection of a 2.5-cm midline precoccygeal mass. After surgical excision of the
      precoccygeal endometriosis, the patient recovered without incident. CONCLUSION:
      Precoccygeal endometriosis is a very rare diagnosis.

PMID- 16449174
TI  - Argon beam coagulator for treatment of hepatic rupture with hemolysis, elevated
      liver enzymes, low platelets (HELLP) syndrome.
AB  - BACKGROUND: We present a case of hepatic rupture secondary to hemolysis, elevated
      liver enzymes, low platelets (HELLP) syndrome and the novel use of the argon beam
      coagulator in achieving hemostasis. CASE: The patient presented at 33 5/7 weeks
      of gestation with elevated liver transaminases, thrombocytopenia, and
      ultrasonographic findings consistent with hepatic rupture. She underwent an
      emergent cesarean delivery followed by exploration of her abdomen by
      hepatobiliary surgeons. An expanding hematoma with rupture of the right lobe of
      the liver was identified. The hematoma was unroofed, and hemostasis was obtained
      using the argon beam coagulator. The patient was discharged home in good
      condition 9 days after surgery. CONCLUSION: With a multidisciplinary approach and
      the argon beam coagulator, we were able to achieve an excellent clinical outcome
      in a patient with hepatic rupture from HELLP syndrome.

PMID- 16449175
TI  - Normal fetus with a twin presenting as both a complete hydatidiform mole and
      placenta previa.
AB  - BACKGROUND: A twin gestation comprising a complete hydatidiform mole and a
      coexisting normal fetus is a rare and high-risk condition. Only a few such
      gestations have resulted in live infants. We report a case with a very large
      molar component presenting as a placenta previa. CASE: A live infant was
      delivered by cesarean at 31 weeks of gestation. The delivery incorporated
      prophylactic temporary balloon occlusion of the internal iliac arteries. The
      patient did not develop persistent gestational trophoblastic disease. CONCLUSION:
      We recommend that intra-arterial balloon catheters be considered before cesarean
      delivery in cases of complete hydatidiform mole with a coexisting normal fetus if
      the molar pregnancy presents as a previa. The size of the molar gestation is not
      an independent risk factor for persistent or metastatic disease.

PMID- 16449176
TI  - Traumatic diaphragmatic rupture: a rare cause of postoperative shortness of
      breath.
AB  - BACKGROUND: Shortness of breath is a common symptom reported by patients after
      gynecologic procedures. Delayed traumatic diaphragmatic rupture is a rare cause
      of shortness of breath. CASE: This report describes the diagnosis and management
      of a patient with a delayed presentation of a ruptured right hemidiaphragm after
      a laparotomy for a pelvic mass. CONCLUSION: Although rare, delayed presentation
      of traumatic diaphragmatic rupture should be considered in patients with a
      history of blunt chest or abdominal trauma as a possible cause of shortness of
      breath in the postoperative setting.

PMID- 16449177
TI  - Cesarean delivery by posterior hysterotomy due to torsion of the pregnant uterus.
AB  - BACKGROUND: We describe a case of cesarean delivery by posterior hysterotomy in a
      woman with uterine torsion secondary to a blocked retroverted uterus. CASE: At 28
      weeks of gestation this patient's fetus was found to have club feet, initially
      suspected to be secondary to sacculation of the posterior uterine segment. At
      cesarean delivery, intraoperative inspection revealed the uterus to be twisted
      180 degrees without evidence of posterior sacculation. The uterine incision was
      performed on the posterior aspect of the lower uterine segment. CONCLUSION: Fixed
      uterine retroversion with torsion is associated with fetal abnormalities and may
      require a posterior uterine incision.

PMID- 16449178
TI  - Candida septicemia in a pregnant woman with hyperemesis receiving parenteral
      nutrition.
AB  - BACKGROUND: Intravascular catheter placement carries the risk of a life
      threatening systemic fungal infection. In addition to antifungal therapy, removal
      of the catheter is often considered to be an important part of management. CASE:
      A 33-year-old multipara with hyperemesis underwent placement of a peripherally
      inserted central catheter for parenteral nutrition. She subsequently developed
      candidemia with both blood and the peripherally inserted central catheter tip
      cultures positive for Candida parapsilosis. The catheter was removed, the patient
      was started on intravenous amphotericin B, and due to side effects, she was
      switched to intravenous fluconazole. She recovered fully, was discharged home on
      oral fluconazole, and delivered a healthy infant at term. CONCLUSION:
      Peripherally inserted central catheter placement may be complicated by
      candidemia. Intravenous fluconazole and removal of the contaminated catheter
      successfully eradicated systemic infection with C parapsilosis.

PMID- 16449179
TI  - Monozygotic twins discordant for monosomy 21 detected by first-trimester nuchal
      translucency screening.
AB  - BACKGROUND: Chromosomal abnormality in one fetus of a monozygotic twin pregnancy
      is rare, and discussion of prenatal detection of such a case offers some insight
      into this clinical problem. CASE: A 28-year-old gravida 1 had ultrasound
      screening at 11 weeks of gestation that revealed a monochorionic, diamniotic twin
      pregnancy with increased nuchal translucency (7.7 mm) in one fetus. Subsequent
      evaluation showed one 45,XY,-21 karyotype and one normal male karyotype. The
      pregnancy was monozygous by DNA analysis. The affected neonate died 5 minutes
      after delivery of both twins by cesarean. CONCLUSION: Monochorionic twins
      discordant for fetal abnormalities can be evaluated with molecular analysis.
      Study of such cases may reveal the extent to which an early diagnosis can lead to
      therapeutic interventions to support survival of the viable twin.

PMID- 16449180
TI  - The forgotten hysterectomy: the first successful abdominal hysterectomy and
      bilateral salpingo-oophorectomy in the United States.
AB  - BACKGROUND: The history of gynecology and surgery in America has been well
      documented. However, a landmark operation took place in 1856 that has gone
      unrecognized in modern surgical texts. CASE: William J. Baker and associates
      performed the first successful abdominal hysterectomy with bilateral salpingo
      oophorectomy in Knoxville, Tennessee on November 13, 1856. The patient recovered
      uneventfully and lived for 34 years after her procedure. CONCLUSION: This case
      has yet to be noted in modern medical history texts. It is important that the
      accomplishments of Dr. Baker and his associates be recognized among the surgical
      pioneers of their day.

PMID- 16449182
TI  - Investment in cancer control and research: a sure bet.

PMID- 16449183
TI  - American Cancer Society guidelines for the early detection of cancer, 2006.
AB  - Each January, the American Cancer Society (ACS) publishes a summary of its
      recommendations for early cancer detection, including guideline updates, emerging
      issues that are relevant to screening for cancer, and a summary of the most
      current data on cancer screening rates for US adults. In 2005, there were no
      updates to ACS guidelines. In this issue of the journal, we summarize the
      guidelines, discuss recent evidence and policy changes that have implications for
      cancer screening, and provide an update of the most recent data pertaining to
      participation rates in cancer screening by age, sex, and insurance status from
      the Centers for Disease Control and Prevention's Behavioral Risk Factor
      Surveillance System.

PMID- 16449185
TI  - Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging
      Manual.
AB  - The sixth edition of the AJCC Cancer Staging Manual contains some of the most
      extensive and significant revisions that have ever been made in the breast cancer
      staging system. The principal changes are related to the size, number, location,
      and method of detection of regional metastases to the lymph nodes. Some changes
      are related to the growing use of new technology (eg, sentinel lymph node biopsy,
      immunohistochemical staining, reverse transcriptase-polymerase chain reaction),
      whereas others are amendments of prior staging criteria, reflecting recent
      clinical evidence or widespread clinical consensus. Available data did not
      support the addition of new prognostic indicators such as histologic tumor grade
      to the tumor-node-metastasis system at this time. Future developments in
      determining breast cancer prognosis will most likely incorporate new approaches
      to identifying the genetic fingerprint of individual tumors.

PMID- 16449184
TI  - Information technology and cancer prevention.
AB  - Information technology is rapidly advancing and making its way into many primary
      care settings. The technology may provide the means to increase the delivery of
      cancer preventive services. The aim of this systematic review is to examine the
      literature on information technology impacts on the delivery of cancer preventive
      services in primary care offices. Thirty studies met our selection criteria.
      Technology interventions studied to date have been limited to some type of
      reminder to either patients or providers. Patient reminders have been mailed
      before appointments, mailed unrelated to an appointment, mailed after a missed
      appointment, or given at the time of an appointment. Telephone call interventions
      have not used technology to automate the calls. Provider interventions have been
      primarily computer-generated reminders at the time of an appointment. However,
      there has been limited use of computer-generated audits, feedback, or report
      cards. The effectiveness of information technology on increasing cancer screening
      was modest at best. The full potential of information technology to unload the
      provider-patient face-to-face encounter has not been examined. There is critical
      need to study these new technologic approaches to understand the impact and
      acceptance by providers and patients.

PMID- 16449186
TI  - Shoichiro Tsukita: a life exploring the molecular architecture of the tight
      junction.
AB  - On December 11, 2005, Shoichiro Tsukita died at the young age of 52, after 14
      months of treatment for cancer. Early in his career, Tsukita succeeded in
      isolating and purifying the adherens junction with his wife Sachiko, an
      accomplishment that he followed up with an impressive series of discoveries of
      cell adhesion and cytoskeletal molecules, including what may have been his
      greatest contribution to the field, the identification of occludin and the
      claudin family of molecules, which were watershed discoveries in the study of the
      molecular nature of tight junctions.

PMID- 16449187
TI  - Disappearance of the budding yeast Bub2-Bfa1 complex from the mother-bound
      spindle pole contributes to mitotic exit.
AB  - Budding yeast spindle position checkpoint is engaged by misoriented spindles and
      prevents mitotic exit by inhibiting the G protein Tem1 through the GTPase
      activating protein (GAP) Bub2/Bfa1. Bub2 and Bfa1 are found on both duplicated
      spindle pole bodies until anaphase onset, when they disappear from the mother
      bound spindle pole under unperturbed conditions. In contrast, when spindles are
      misoriented they remain symmetrically localized at both SPBs. Thus, symmetric
      localization of Bub2/Bfa1 might lead to inhibition of Tem1, which is also present
      at SPBs. Consistent with this hypothesis, we show that a Bub2 version
      symmetrically localized on both SPBs throughout the cell cycle prevents mitotic
      exit in mutant backgrounds that partially impair it. This effect is Bfa1
      dependent and can be suppressed by high Tem1 levels. Bub2 removal from the mother
      bound SPB requires its GAP activity, which in contrast appears to be dispensable
      for Tem1 inhibition. Moreover, it correlates with the passage of one spindle pole
      through the bud neck because it needs septin ring formation and bud neck kinases.

PMID- 16449188
TI  - Asynchronous nuclear division cycles in multinucleated cells.
AB  - Synchronous mitosis is common in multinucleated cells. We analyzed a unique
      asynchronous nuclear division cycle in a multinucleated filamentous fungus,
      Ashbya gossypii. Nuclear pedigree analysis and observation of GFP-labeled spindle
      pole bodies demonstrated that neighboring nuclei in A. gossypii cells are in
      different cell cycle stages despite close physical proximity. Neighboring nuclei
      did not differ significantly in their patterns of cyclin protein localization
      such that both G1 and mitotic cyclins were present regardless of cell cycle
      stage, suggesting that the complete destruction of cyclins is not occurring in
      this system. Indeed, the expression of mitotic cyclin lacking NH(2)-terminal
      destruction box sequences did not block cell cycle progression. Cells lacking
      AgSic1p, a predicted cyclin-dependent kinase (CDK) inhibitor, however, showed
      aberrant multipolar spindles and fragmented nuclei that are indicative of flawed
      mitoses. We hypothesize that the continuous cytoplasm in these cells promoted the
      evolution of a nuclear division cycle in which CDK inhibitors primarily control
      CDK activity rather than oscillating mitotic cyclin proteins.

PMID- 16449189
TI  - Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response
      and are required for ER-associated degradation.
AB  - Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be
      refolded or degraded to maintain the homeostasis of the ER. Components of both
      productive folding and ER-associated degradation (ERAD) mechanisms are known to
      be up-regulated by the unfolded protein response (UPR). We describe two novel
      components of mammalian ERAD, Derlin-2 and -3, which show weak homology to Der1p,
      a transmembrane protein involved in yeast ERAD. Both Derlin-2 and -3 are up
      regulated by the UPR, and at least Derlin-2 is a target of the IRE1 branch of the
      response, which is known to up-regulate ER degradation enhancing alpha
      mannosidase-like protein (EDEM) and EDEM2, receptor-like molecules for misfolded
      glycoprotein. Overexpression of Derlin-2 or -3 accelerated degradation of
      misfolded glycoprotein, whereas their knockdown blocked degradation. Derlin-2 and
      -3 are associated with EDEM and p97, a cytosolic ATPase responsible for
      extraction of ERAD substrates. These findings indicate that Derlin-2 and -3
      provide the missing link between EDEM and p97 in the process of degrading
      misfolded glycoproteins.

PMID- 16449190
TI  - Adaptation and increased susceptibility to infection associated with constitutive
      expression of misfolded SP-C.
AB  - Mutations in the gene encoding SP-C (surfactant protein C; SFTPC) have been
      linked to interstitial lung disease (ILD) in children and adults. Expression of
      the index mutation, SP-C(Deltaexon4), in transiently transfected cells and type
      II cells of transgenic mice resulted in misfolding of the proprotein, activation
      of endoplasmic reticulum (ER) stress pathways, and cytotoxicity. In this study,
      we show that stably transfected cells adapted to chronic ER stress imposed by the
      constitutive expression of SP-C(Deltaexon4) via an NF-kappaB-dependent pathway.
      However, the infection of cells expressing SP-C(Deltaexon4) with respiratory
      syncytial virus resulted in significantly enhanced cytotoxicity associated with
      accumulation of the mutant proprotein, pronounced activation of the unfolded
      protein response, and cell death. Adaptation to chronic ER stress imposed by
      misfolded SP-C was associated with increased susceptibility to viral-induced cell
      death. The wide variability in the age of onset of ILD in patients with SFTPC
      mutations may be related to environmental insults that ultimately overwhelm the
      homeostatic cytoprotective response.

PMID- 16449191
TI  - AP-2alpha: a regulator of EGF receptor signaling and proliferation in skin
      epidermis.
AB  - AP-2 transcription factors have been implicated in epidermal biology, but their
      functional significance has remained elusive. Using conditional knockout
      technology, we show that AP-2alpha is essential for governing the balance between
      growth and differentiation in epidermis. In vivo, epidermis lacking AP-2alpha
      exhibits elevated expression of the epidermal growth factor receptor (EGFR) in
      the differentiating layers, resulting in hyperproliferation when the receptors
      are activated. Chromatin immunoprecipitation and promoter activity assays
      identify EGFR as a direct target gene for AP-2alpha repression, and, in the
      absence of AP-2alpha, this is manifested primarily in excessive EGF-dependent
      phosphoinositol-3 kinase/Akt activity. Together, our findings unveil a hitherto
      unrecognized repressive role for AP-2alpha in governing EGFR gene transcription
      as cells exit the basal layer and withdraw from the cell cycle. These results
      provide insights into why elevated AP-2alpha levels are often associated with
      terminal differentiation and why tumor cells often display reduced AP-2alpha and
      elevated EGFR proteins.

PMID- 16449192
TI  - P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen
      matrix contraction by human fibroblasts.
AB  - Fibroblast three-dimensional collagen matrix culture provides a tissue-like model
      that can be used to analyze cell form and function. The physiological agonists
      platelet-derived growth factor (PDGF) and lysophosphatidic acid (LPA) both
      stimulate human fibroblasts to contract floating collagen matrices. In this
      study, we show that the PDGF and LPA signaling pathways required for matrix
      contraction converge on p21-activated kinase 1 (PAK1) and its downstream effector
      cofilin1 and that contraction depends on cellular ruffling activity, rather than
      on the protrusion and retraction of cellular dendritic extensions. We also show
      that, depending on the agonist, different Rho effectors cooperate with PAK1 to
      regulate matrix contraction, Rho kinase in the case of PDGF and mDia1 in the case
      of LPA. These findings establish a unified framework for understanding the cell
      signaling pathways involved in fibroblast contraction of floating collagen
      matrices.

PMID- 16449193
TI  - Salamander limb regeneration involves the activation of a multipotent skeletal
      muscle satellite cell population.
AB  - In contrast to mammals, salamanders can regenerate complex structures after
      injury, including entire limbs. A central question is whether the generation of
      progenitor cells during limb regeneration and mammalian tissue repair occur via
      separate or overlapping mechanisms. Limb regeneration depends on the formation of
      a blastema, from which the new appendage develops. Dedifferentiation of stump
      tissues, such as skeletal muscle, precedes blastema formation, but it was not
      known whether dedifferentiation involves stem cell activation. We describe a
      multipotent Pax7+ satellite cell population located within the skeletal muscle of
      the salamander limb. We demonstrate that skeletal muscle dedifferentiation
      involves satellite cell activation and that these cells can contribute to new
      limb tissues. Activation of salamander satellite cells occurs in an analogous
      manner to how the mammalian myofiber mobilizes stem cells during skeletal muscle
      tissue repair. Thus, limb regeneration and mammalian tissue repair share common
      cellular and molecular programs. Our findings also identify satellite cells as
      potential targets in promoting mammalian blastema formation.

PMID- 16449194
TI  - Neuronal cotransport of glycine receptor and the scaffold protein gephyrin.
AB  - The dynamics of postsynaptic receptor scaffold formation and remodeling at
      inhibitory synapses remain largely unknown. Gephyrin, which is a multimeric
      scaffold protein, interacts with cytoskeletal elements and stabilizes glycine
      receptors (GlyRs) and individual subtypes of gamma-aminobutyric acid A receptors
      at inhibitory postsynaptic sites. We report intracellular mobility of gephyrin
      transports packets over time. Gephyrin units enter and exit active synapses
      within several minutes. In addition to previous reports of GlyR-gephyrin
      interactions at plasma membranes, we show cosedimentation and
      coimmunoprecipitation of both proteins from vesicular fractions. Moreover, GlyR
      and gephyrin are cotransported within neuronal dendrites and further
      coimmunoprecipitate and colocalize with the dynein motor complex. As a result,
      the blockade of dynein function or dynein-gephyrin interaction, as well as the
      depolymerization of microtubules, interferes with retrograde gephyrin
      recruitment. Our data suggest a GlyR-gephyrin-dynein transport complex and
      support the concept that gephyrin-motor interactions contribute to the dynamic
      and activity-dependent rearrangement of postsynaptic GlyRs, a process thought to
      underlie the regulation of synaptic strength.

PMID- 16449195
TI  - Localized recruitment and activation of RhoA underlies dendritic spine morphology
      in a glutamate receptor-dependent manner.
AB  - Actin is the major cytoskeletal source of dendritic spines, which are highly
      specialized protuberances on the neuronal surface where excitatory synaptic
      transmission occurs (Harris, K.M., and S.B. Kater. 1994. Annu. Rev. Neurosci.
      17:341-371; Yuste, R., and D.W. Tank. 1996. Neuron. 16:701-716). Stimulation of
      excitatory synapses induces changes in spine shape via localized rearrangements
      of the actin cytoskeleton (Matus, A. 2000. Science. 290:754-758; Nagerl, U.V., N.
      Eberhorn, S.B. Cambridge, and T. Bonhoeffer. 2004. Neuron. 44:759-767). However,
      what remains elusive are the precise molecular mechanisms by which different
      neurotransmitter receptors forward information to the underlying actin
      cytoskeleton. We show that in cultured hippocampal neurons as well as in whole
      brain synaptosomal fractions, RhoA associates with glutamate receptors (GluRs) at
      the spine plasma membrane. Activation of ionotropic GluRs leads to the detachment
      of RhoA from these receptors and its recruitment to metabotropic GluRs.
      Concomitantly, this triggers a local reduction of RhoA activity, which, in turn,
      inactivates downstream kinase RhoA-specific kinase, resulting in restricted actin
      instability and dendritic spine collapse. These data provide a direct mechanistic
      link between neurotransmitter receptor activity and the changes in spine shape
      that are thought to play a crucial role in synaptic strength.

PMID- 16449198
TI  - Formation of supported phospholipid bilayers on molecular surfaces: role of
      surface charge density and electrostatic interaction.
AB  - Electrostatic interaction is known to play important roles in the adsorption of
      charged lipids on oppositely charged surfaces. Here we show that, even for charge
      neutral (zwitterionic) lipids, electrostatic interaction is critical in
      controlling the adsorption and fusion of lipid vesicles to form supported
      phospholipid bilayers (SPBs) on surfaces. We use terminally functionalized
      alkanethiol self-assembled monolayers (SAMs) to systematically control the
      surface charge density. Charge neutral egg phophatidylcholine (eggPC) vesicles
      readily fuse into SPBs on either a positively charged 11-aminino-1-undecanethiol
      SAM or a negatively charged 10-carboxy-1-decanethiol SAM when the density of
      surface charge groups is > or = 80%. These processes depend critically on the
      buffer environment: fusion of adsorbed vesicles to form SPBs on each charged
      molecular surface does not occur when the molecular ion of the buffer used is of
      the opposite charge type. We attribute this to the high entropic repulsion
      (electric double layer repulsion) due to the large size of molecular counterions.
      On the other hand, such a critical dependence on buffer type is not observed when
      charged lipids are used. This study suggests the general importance of
      controlling electrostatic interaction in the formation of stable SPBs.

PMID- 16449196
TI  - Evolution of a neuroprotective function of central nervous system myelin.
AB  - The central nervous system (CNS) of terrestrial vertebrates underwent a prominent
      molecular change when a tetraspan membrane protein, myelin proteolipid protein
      (PLP), replaced the type I integral membrane protein, P0, as the major protein of
      myelin. To investigate possible reasons for this molecular switch, we genetically
      engineered mice to express P0 instead of PLP in CNS myelin. In the absence of
      PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was
      identical to mouse PNS myelin, where P0 is the major structural protein today.
      The PLP-P0 shift resulted in reduced myelin internode length, degeneration of
      myelinated axons, severe neurological disability, and a 50% reduction in
      lifespan. Mice with equal amounts of P0 and PLP in CNS myelin had a normal
      lifespan and no axonal degeneration. These data support the hypothesis that the
      P0-PLP shift during vertebrate evolution provided a vital neuroprotective
      function to myelin-forming CNS glia.

PMID- 16449197
TI  - Polynucleotide adsorption to negatively charged surfaces in divalent salt
      solutions.
AB  - Polynucleotide adsorption to negatively charged surfaces via divalent ions is
      extensively used in the study of biological systems. We analyze here the
      adsorption mechanism via a self-consistent mean-field model that includes the pH
      effect on the surface-charge density and the interactions between divalent ions
      and surface groups. The adsorption is driven by the cooperative effect of
      divalent metal ion condensation along polynucleotides and their reaction with the
      surface groups. Although the apparent reaction constants are enhanced by the
      presence of polynucleotides, the difference between reaction constants of
      different divalent ions at the ideal condition explains why not all divalent
      cations mediate DNA adsorption onto anionic surfaces. Calculated divalent salt
      concentration and pH value variations on polynucleotide adsorption are consistent
      with atomic force microscope results. Here we use long-period x-ray standing
      waves to study the adsorption of mercurated-polyuridylic acid in a ZnCl2 aqueous
      solution onto a negatively charged hydroxyl-terminated silica surface. These in
      situ x-ray measurements, which simultaneously reveal the Hg and Zn distribution
      profiles along the surface normal direction, are in good agreement with our
      model. The model also provides the effects of polyelectrolyte line-charge density
      and monovalent salt on adsorption.

PMID- 16449199
TI  - Therapeutic protein transduction of mammalian cells and mice by nucleic acid-free
      lentiviral nanoparticles.
AB  - The straightforward production and dose-controlled administration of protein
      therapeutics remain major challenges for the biopharmaceutical manufacturing and
      gene therapy communities. Transgenes linked to HIV-1-derived vpr and pol-based
      protease cleavage (PC) sequences were co-produced as chimeric fusion proteins in
      a lentivirus production setting, encapsidated and processed to fusion peptide
      free native protein in pseudotyped lentivirions for intracellular delivery and
      therapeutic action in target cells. Devoid of viral genome sequences, protein
      transducing nanoparticles (PTNs) enabled transient and dose-dependent delivery of
      therapeutic proteins at functional quantities into a variety of mammalian cells
      in the absence of host chromosome modifications. PTNs delivering Manihot
      esculenta linamarase into rodent or human, tumor cell lines and spheroids
      mediated hydrolysis of the innocuous natural prodrug linamarin to cyanide and
      resulted in efficient cell killing. Following linamarin injection into nude mice,
      linamarase-transducing nanoparticles impacted solid tumor development through the
      bystander effect of cyanide.

PMID- 16449200
TI  - Base-stacking and base-pairing contributions into thermal stability of the DNA
      double helix.
AB  - Two factors are mainly responsible for the stability of the DNA double helix:
      base pairing between complementary strands and stacking between adjacent bases.
      By studying DNA molecules with solitary nicks and gaps we measure temperature and
      salt dependence of the stacking free energy of the DNA double helix. For the
      first time, DNA stacking parameters are obtained directly (without extrapolation)
      for temperatures from below room temperature to close to melting temperature. We
      also obtain DNA stacking parameters for different salt concentrations ranging
      from 15 to 100 mM Na+. From stacking parameters of individual contacts, we
      calculate base-stacking contribution to the stability of A*T- and G*C-containing
      DNA polymers. We find that temperature and salt dependences of the stacking term
      fully determine the temperature and the salt dependence of DNA stability
      parameters. For all temperatures and salt concentrations employed in present
      study, base-stacking is the main stabilizing factor in the DNA double helix. A*T
      pairing is always destabilizing and G*C pairing contributes almost no
      stabilization. Base-stacking interaction dominates not only in the duplex overall
      stability but also significantly contributes into the dependence of the duplex
      stability on its sequence.

PMID- 16449201
TI  - Nucleic acid binding and chaperone properties of HIV-1 Gag and nucleocapsid
      proteins.
AB  - The Gag polyprotein of HIV-1 is essential for retroviral replication and
      packaging. The nucleocapsid (NC) protein is the primary region for the
      interaction of Gag with nucleic acids. In this study, we examine the interactions
      of Gag and its NC cleavage products (NCp15, NCp9 and NCp7) with nucleic acids
      using solution and single molecule experiments. The NC cleavage products bound
      DNA with comparable affinity and strongly destabilized the DNA duplex. In
      contrast, the binding constant of Gag to DNA was found to be approximately 10
      fold higher than that of the NC proteins, and its destabilizing effect on dsDNA
      was negligible. These findings are consistent with the primary function of Gag as
      a nucleic acid binding and packaging protein and the primary function of the NC
      proteins as nucleic acid chaperones. Also, our results suggest that NCp7's
      capability for fast sequence-nonspecific nucleic acid duplex destabilization, as
      well as its ability to facilitate nucleic acid strand annealing by inducing
      electrostatic attraction between strands, likely optimize the fully processed NC
      protein to facilitate complex nucleic acid secondary structure rearrangements. In
      contrast, Gag's stronger DNA binding and aggregation capabilities likely make it
      an effective chaperone for processes that do not require significant duplex
      destabilization.

PMID- 16449203
TI  - HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the
      2' OH of the 3' terminal nucleotide.
AB  - microRNAs (miRNAs) and small interfering RNAs (siRNAs) in plants bear a methyl
      group on the ribose of the 3' terminal nucleotide. We showed previously that the
      methylation of miRNAs and siRNAs requires the protein HEN1 in vivo and that
      purified HEN1 protein methylates miRNA/miRNA* duplexes in vitro. In this study,
      we show that HEN1 methylates both miRNA/miRNA* and siRNA/siRNA* duplexes in vitro
      with a preference for 21-24 nt RNA duplexes with 2 nt overhangs. We also
      demonstrate that HEN1 deposits the methyl group on to the 2' OH of the 3'
      terminal nucleotide. Among various modifications that can occur on the ribose of
      the terminal nucleotide, such as 2'-deoxy, 3'-deoxy, 2'-O-methyl and 3'-O-methyl,
      only 2'-O-methyl on a small RNA inhibits the activity of yeast poly(A) polymerase
      (PAP). These findings indicate that HEN1 specifically methylates miRNAs and
      siRNAs and implicate the importance of the 2'-O-methyl group in the biology of
      RNA silencing.

PMID- 16449202
TI  - Deletion of the Tetrahymena thermophila rDNA replication fork barrier region
      disrupts macronuclear rDNA excision and creates a fragile site in the
      micronuclear genome.
AB  - During macronuclear development the Tetrahymena thermophila ribosomal RNA gene is
      excised from micronuclear chromosome 1 by site-specific cleavage at chromosome
      breakage sequence (Cbs) elements, rearranged into a 'palindromic' 21 kb
      minichromosome and extensively amplified. Gene amplification initiates from
      origins in the 5' non-transcribed spacer, and forks moving toward the center of
      the palindrome arrest at a developmentally regulated replication fork barrier
      (RFB). The RFB is inactive during vegetative cell divisions, suggesting a role in
      the formation or amplification of macronuclear rDNA. Using micronuclear
      (germline) transformation, we show that the RFB region facilitates Cbs-mediated
      excision. Deletion of the RFB inhibits chromosome breakage in a sub-population of
      developing macronuclei and promotes alternative processing by a Cbs-independent
      mechanism. Remarkably, the RFB region prevents spontaneous breakage of chromosome
      1 in the diploid micronucleus. Strains heterozygous for DeltaRFB and wild-type
      rDNA lose the DeltaRFB allele and distal left arm of chromosome 1 during
      vegetative propagation. The wild-type chromosome is subsequently fragmented near
      the rDNA locus, and both homologs are progressively eroded, suggesting that
      broken micronuclear chromosomes are not 'healed' by telomerase. Deletion of this
      363 bp segment effectively creates a fragile site in the micronuclear genome,
      providing the first evidence for a non-telomere cis-acting determinant that
      functions to maintain the structural integrity of a mitotic eukaryotic
      chromosome.

PMID- 16449204
TI  - Similarities and differences in interaction of K+ and Na+ with condensed ordered
      DNA. A molecular dynamics computer simulation study.
AB  - Four 20 ns molecular dynamics simulations have been performed with two
      counterions, K+ or Na+, at two water contents, 15 or 20 H2O per nucleotide. A
      hexagonal simulation cell comprised of three identical DNA decamers [d(5'
      ATGCAGTCAG) x d(5'-TGACTGCATC)] with periodic boundary condition along the DNA
      helix was used. The simulation setup mimics the DNA state in oriented DNA fibers
      or in crystals of DNA oligomers. Variation of counterion nature and water content
      do not alter averaged DNA structure. K+ and Na+ binding to DNA are different. K+
      binds to the electronegative sites of DNA bases in the major and the minor
      grooves, while Na+ interacts preferentially with the phosphate groups. Increase
      of water causes a shift of both K+ and Na+ from the first hydration shell of
      O1P/O2P and of the DNA bases in the minor groove with lesser influence for the
      cation binding to the bases in the major groove. Mobility of both water and
      cations in the K-DNA systems is faster than in the Na-DNA systems: Na+ organizes
      and immobilizes water structure around itself and near DNA while for K+ water is
      less organized and more dynamic.

PMID- 16449205
TI  - Hfq variant with altered RNA binding functions.
AB  - The interaction between Hfq and RNA is central to multiple regulatory processes.
      Using site-directed mutagenesis, we have found a missense mutation in Hfq (V43R)
      which strongly affects2 the RNA binding capacity of the Hfq protein and its
      ability to stimulate poly(A) tail elongation by poly(A)-polymerase in vitro. In
      vivo, overexpression of this Hfq variant fails to stimulate rpoS-lacZ expression
      and does not restore a normal growth rate in hfq null mutant. Cells in which the
      wild-type gene has been replaced by the hfqV43R allele exhibit a phenotype
      intermediate between those of the wild-type and of the hfq minus or null strains.
      This missense mutation derepresses Hfq synthesis. However, not all Hfq functions
      are affected by this mutation. For example, HfqV43R represses OppA synthesis as
      strongly as the wild-type protein. The dominant negative effect of the V43R
      mutation over the wild-type allele suggests that hexamers containing variant and
      genuine subunits are presumably not functional. Finally, molecular dynamics
      studies indicate that the V43R substitution mainly changes the position of the
      K56 and Y55 side chains involved in the Hfq-RNA interaction but has probably no
      effect on the folding and the oligomerization of the protein.

PMID- 16449206
TI  - Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming
      oligonucleotides targeting the c-myc gene in prostate cancer cells.
AB  - Covalent attachment of intercalating agents to triplex-forming oligonucleotides
      (TFOs) is a promising strategy to enhance triplex stability and biological
      activity. We have explored the possibility to use the anticancer drug daunomycin
      as triplex stabilizing agent. Daunomycin-conjugated TFOs (dauno-TFOs) bind with
      high affinity and maintain the sequence-specificity required for targeting
      individual genes in the human genome. Here, we examined the effects of two dauno
      TFOs targeting the c-myc gene on gene expression, cell proliferation and
      survival. The dauno-TFOs were directed to sequences immediately upstream (dauno
      GT11A) and downstream (dauno-GT11B) the major transcriptional start site in the c
      myc gene. Both dauno-TFOs were able to down-regulate promoter activity and
      transcription of the endogenous gene. Myc-targeted dauno-TFOs inhibited growth
      and induced apoptosis of prostate cancer cells constitutively expressing the
      gene. Daunomycin-conjugated control oligonucleotides with similar sequences had
      only minimal effects, confirming that the activity of dauno-TFOs was sequence
      specific and triplex-mediated. To test the selectivity of dauno-TFOs, we examined
      their effects on growth of normal human fibroblasts, which express low levels of
      c-myc. Despite their ability to inhibit c-myc transcription, both dauno-TFOs
      failed to inhibit growth of normal fibroblasts at concentrations that inhibited
      growth of prostate cancer cells. In contrast, daunomycin inhibited equally
      fibroblasts and prostate cancer cells. Thus, daunomycin per se did not contribute
      to the antiproliferative activity of dauno-TFOs, although it greatly enhanced
      their ability to form stable triplexes at the target sites and down-regulate c
      myc. Our data indicate that dauno-TFOs are attractive gene-targeting agents for
      development of new cancer therapeutics.

PMID- 16449207
TI  - The Werner syndrome protein operates in base excision repair and cooperates with
      DNA polymerase beta.
AB  - Genome instability is a characteristic of cancer and aging, and is a hallmark of
      the premature aging disorder Werner syndrome (WS). Evidence suggests that the
      Werner syndrome protein (WRN) contributes to the maintenance of genome integrity
      through its involvement in DNA repair. In particular, biochemical evidence
      indicates a role for WRN in base excision repair (BER). We have previously
      reported that WRN helicase activity stimulates DNA polymerase beta (pol beta)
      strand displacement synthesis in vitro. In this report we demonstrate that WRN
      exonuclease activity can act cooperatively with pol beta, a polymerase lacking 3'
      5' proofreading activity. Furthermore, using small interference RNA technology,
      we demonstrate that WRN knockdown cells are hypersensitive to the alkylating
      agent methyl methanesulfonate, which creates DNA damage that is primarily
      repaired by the BER pathway. In addition, repair assays using whole cell extracts
      from WRN knockdown cells indicate a defect in long patch (LP) BER. These findings
      demonstrate that WRN plays a direct role in the repair of methylation-induced DNA
      damage, and suggest a role for both WRN helicase and exonuclease activities
      together with pol beta during LP BER.

PMID- 16449209
TI  - Notable steps in obtaining improved estimates for glomerular filtration rate.

PMID- 16449210
TI  - Performance evaluation and subsequent clinical experience with the Abbott
      Automated Architect STAT Troponin-I assay.
AB  - BACKGROUND: Cardiac troponins are specific biochemical markers of myocardial
      injury used in the diagnosis of acute myocardial disease and cardiac risk
      stratification. To avoid misclassification of patients, troponin assays must
      demonstrate precision at the low end of the measuring range. We report our
      evaluation of the Architect STAT Troponin-I assay (Abbott Diagnostics),
      comparison of low-positive results with 2 other assays, and occurrence of
      heterophile antibody interference in the assay. METHODS: We assessed analytical
      performance on the ci8200 according to CLSI protocols, using quality-control and
      patient samples. Our healthy reference population included 480 blood donors. For
      correlation studies against the AxSYM first-generation cTnI (Abbott Diagnostics)
      and Access second-generation AccuTnI (Beckman Coulter) assays, we used 339
      samples from hospital patients. RESULTS: The CV of the Architect STAT Troponin-I
      assay was 10% near the 99th percentile for the reference population (0.03
      microg/L). Comparison with the AxSYM first-generation cTnI assay showed good
      correlation at higher concentrations, but better sensitivity of the Architect
      cTnI assay at low concentrations, which were clinically relevant as shown by
      review of patient histories. Correlation was good at the low end of the measuring
      range with the Access second-generation AccuTnI. Over the last 12 months we have
      identified 6 patients with heterophile antibodies causing positive interference.
      CONCLUSIONS: The Architect STAT Troponin-I assay provides highly sensitive
      measurement of cTnI with a CV of 10% near the upper limit of a reference
      population; however, heterophile antibodies can interfere with this assay.

PMID- 16449208
TI  - Sequence effects of aminofluorene-modified DNA duplexes: thermodynamic and
      circular dichroism properties.
AB  - Circular dichroism (CD) and UV-melting experiments were conducted with 16
      oligodeoxynucleotides modified by the carcinogen 2-aminofluorene, whose sequence
      around the lesion was varied systematically [d(CTTCTNG[AF]NCCTC), N = G, A, C,
      T], to gain insight into the factors that determine the equilibrium between base
      displaced stacked (S) and external B-type (B) duplex conformers. Differing
      stabilities among the duplexes can be attributed to different populations of S
      and B conformers. The AF modification always resulted in sequence-dependent
      thermal (T(m)) and thermodynamic (-DeltaG degrees ) destabilization. The
      population of B-type conformers derived from eight selected duplexes (i.e. -AG*N-
      and -CG*N-) was inversely proportional to the -DeltaG degrees and T(m) values,
      which highlights the importance of carcinogen/base stacking in duplex
      stabilization even in the face of disrupted Watson-Crick base pairing in S
      conformation. CD studies showed that the extent of the adduct-induced negative
      ellipticities in the 290-350 nm range is correlated linearly with -DeltaG degrees
      and T(m), but inversely with the population of B-type conformations. Taken
      together, these results revealed a unique interplay between the extent of
      carcinogenic interaction with neighboring base pairs and the thermodynamic
      properties of the AF-modified duplexes. The sequence-dependent S/B
      heterogeneities have important implications in understanding how arylamine-DNA
      adducts are recognized in nucleotide excision repair.

PMID- 16449212
TI  - Development of a 5'-nuclease real-time PCR assay targeting fliP for the rapid
      identification of Burkholderia mallei in clinical samples.
AB  - BACKGROUND: Burkholderia mallei is a potential biological agent that causes
      glanders or farcy in solipeds, a disease notifiable to the Office International
      des Epizooties (OIE). The number of reported outbreaks has increased steadily
      during the last decade, but diagnosis is hampered by the low bacterial load in
      infected tissues and excretions. METHODS: We developed a B. mallei-specific 5'
      nuclease real-time PCR assay that targets the fliP gene of B. mallei and includes
      an internal amplification control. Specificity was assessed with 19 B. mallei
      strains, 27 Burkholderia pseudomallei strains, other Burkholderia strains of 29
      species, and clinically relevant non-Burkholderia organisms. RESULTS:
      Amplification products were observed in all B. mallei strains but in no other
      bacteria. The linear range of the B. mallei real-time PCR covered concentrations
      from 240 pg to 70 fg of bacterial DNA/reaction. The detection limit was 60 fg of
      B. mallei DNA. The clinical applicability of the assay was demonstrated by use of
      organ samples from diseased horses of a recent outbreak that was reported to the
      OIE by the United Arab Emirates in 2004. CONCLUSIONS: Compared with conventional
      PCR, our rapid 5'-nuclease real-time PCR assay for the specific identification of
      B. mallei has a lower risk of carryover contamination and eliminates the need for
      post-PCR manipulations. This real-time PCR assay also shortens the turnaround
      time for results and has the potential for automation.

PMID- 16449211
TI  - Atorvastatin reduces the expression of COX-2 mRNA in peripheral blood monocytes
      from patients with acute myocardial infarction and modulates the early
      inflammatory response.
AB  - BACKGROUND: We examined the effect of atorvastatin on the expression of COX-2 in
      peripheral blood monocytes from patients with early stage of acute myocardial
      infarction (AMI), and the plasma C-reactive protein (CRP) concentrations were
      also examined. METHODS: Patients with AMI (n = 40) and with stable coronary heart
      disease (CHD; n = 18) were registered, and patients with AMI were randomly
      separated to a group that received routine therapy (group A, n = 20) or to a
      group that received routine therapy plus atorvastatin at 20 mg/day (group B, n =
      20) for a week. Peripheral blood monocytes from patients with AMI both before and
      after treatment and from patients with stable CHD were isolated and cultured for
      24 h. COX-2 mRNA expression was analyzed by reverse transcription-PCR. We
      measured concentrations of CRP in plasma by ELISA. RESULTS: COX-2 expression was
      activated in peripheral blood monocytes from patients with AMI [0.92 (0.13)]
      compared with patients with stable CHD [0.19 (0.08)]; after a week of treatment,
      COX-2 expression in group B (reduced by 66%) was obviously lower than in group A
      (reduced by 24%; P <0.05). Plasma concentrations of CRP from patients with AMI
      [43.3 (14.9) mg/L] were increased compared with those from patients with stable
      CHD [1.65 (0.78) mg/L; P <0.05]; after a week of treatment, CRP concentrations in
      group B (reduced by 62%) were lower than in group A (reduced by 35%; P <0.05).
      COX-2 expression in peripheral blood monocytes from patients with AMI was
      positively correlated with plasma CRP concentration (r = 0.662; P <0.05).
      CONCLUSIONS: COX-2 may promote acute inflammatory process after AMI. Atorvastatin
      may improve the antiinflammatory effects through the COX-2 pathway.

PMID- 16449213
TI  - Human ATP-binding cassette transporter TaqMan low-density array: analysis of
      macrophage differentiation and foam cell formation.
AB  - BACKGROUND: ATP-binding cassette (ABC) transporters cause various diseases and
      regulate many physiologic processes, such as lipid homeostasis, iron transport,
      and immune mechanisms. Several ABC transporters are involved in bile acid,
      phospholipid, and sterol transport, and their expression is itself controlled by
      lipids. In addition, ABC proteins mediate drug export in tumor cells and promote
      the development of multidrug resistance. METHODS: We created an ABC Transporter
      TaqMan Low-Density Array based on an Applied Biosystems 7900HT Micro Fluidic
      Card. We used a 2-microL reaction well with 2 ng of sample. To evaluate this
      method for lipidomic research and to characterize expression patterns of ABC
      transporters in cells relevant for atherosclerosis research, we monitored mRNA
      expression in human primary monocytes, in vitro-differentiated macrophages, and
      cells stimulated with the liver-X-receptor and retinoid-X-receptor agonists
      T0901317 and 9-cis retinoic acid, mimicking sterol loading. RESULTS: The method
      enabled simultaneous analysis of 47 human ABC transporters and the reference gene
      18S rRNA in 2 replicates of 4 samples per run. CONCLUSIONS: The new system uses
      only 2 ng of sample and small volumes of reagent, and the precaptured primers and
      probes avoided labor-intensive pipetting steps. The ABC Transporter TaqMan Low
      Density Array may be a useful tool to monitor dysregulated ABC transporter mRNA
      profiles in human lipid disorders and cancer-related multidrug resistance and to
      analyze the pharmacologic and metabolic regulation of ABC transporter expression
      important for drug development in large-scale screening approaches.

PMID- 16449214
TI  - Time profile of appearance and disappearance of circulating placenta-derived mRNA
      in maternal plasma.
AB  - BACKGROUND: Fetal RNA of placental origin has been detected in the plasma of
      pregnant women, but the timing of the first appearance and the detailed kinetics
      of postdelivery clearance of such circulating RNA have not been studied. METHODS:
      To address the timing of the first appearance of circulating placental RNA, we
      collected serial maternal blood samples from 47 women who had conceived by
      assisted reproductive procedures. To address the postdelivery clearance kinetics,
      we collected serial postdelivery blood samples from 6 pregnant women who had
      delivered by cesarean section. Placenta-derived transcripts were sought by real
      time quantitative reverse transcription-PCR. RESULTS: The earliest gestational
      age at which human placental lactogen and human chorionic gonadotropin beta
      subunit mRNAs were detectable in a proportion of the pregnant women was the 4th
      week of gestation. The postdelivery study indicated that the median apparent half
      life for the clearance of human placental lactogen mRNA was 14 min. CONCLUSIONS:
      Placenta-derived mRNA can be found in maternal plasma from very early on in
      gestation, suggesting a possible role for early noninvasive prenatal diagnosis or
      monitoring. The rapid kinetics of circulating placental mRNA suggest that its
      plasma concentrations may be used to monitor recent physiologic or pathologic
      events.

PMID- 16449215
TI  - Real-time PCR detection of parapoxvirus DNA.
AB  - BACKGROUND: Detection of parapoxviruses is important in various animals as well
      as in humans as zoonotic infections. Reliable detection of parapoxviruses is
      fundamental for the exclusion of other rash-causing illnesses, for both
      veterinarians and medical practitioners. To date, however, no real-time PCR assay
      for the detection of parapoxviruses has been reported. METHODS: A minor groove
      binder-based quantitative real-time PCR assay targeting the B2L gene of
      parapoxviruses was developed on the ABI Prism and the LightCycler platforms.
      RESULTS: The real-time PCR assay successfully amplified DNA fragments from a
      total of 41 parapoxvirus strains and isolates representing the species orf virus,
      bovine papular stomatitis virus, pseudocowpoxvirus, and sealpoxvirus. Probit
      analysis gave a limit of detection of 4.7 copies per assay (95% confidence
      interval, 3.7-6.8 copies per reaction). Scabs contain a sufficient amount of
      parapoxvirus DNA and can therefore be used for PCR without any DNA preparation
      step. No cross-reactivity to human, bovine, or sheep genomic DNA or other DNA
      viruses, including orthopoxviruses, molluscum contagiosum viruses, and yaba-like
      disease viruses, was observed. CONCLUSION: The presented assay is suitable for
      the detection of parapoxvirus infections in clinical material of human and animal
      origin.

PMID- 16449216
TI  - Use of RNA fluorescence in situ hybridization in the prenatal molecular diagnosis
      of myotonic dystrophy type I.
AB  - BACKGROUND: Myotonic dystrophy type 1 (DM1; OMIM #160900) is an autosomal
      dominant genetic disorder with multisystemic clinical features associated with a
      CTG expansion in the 3' untranslated region of the DMPK gene on chromosome
      19q13.3. A long-PCR protocol to detect the DM1 expansion is rapid, sensitive, and
      accurate, but interpretative limitations can occur when the expansion size
      exceeds the PCR amplification range and in cases of somatic mosaicism. METHODS:
      To overcome these problems, we used RNA fluorescence in situ hybridization (RNA
      FISH) to study cultured cells derived from chorionic villus samples (CVS) with
      the DM1 mutation. The RNA-FISH method is designed to detect the distinctive DM1
      cellular phenotype, characterized by the presence of nuclei with focal
      ribonuclear inclusions (foci) containing the DMPK expanded transcripts. We
      analyzed 6 CVS from DM1-predicted pregnancies and 6 CVS from DM1-negative
      pregnancies. RESULTS: In 4 DM1-predicted fetuses with a CTG expansion >200 CTG,
      varying numbers of ribonuclear inclusions were clearly visible in all cells. One
      case with a somatic mosaicism for the DMPK mutation showed 15% of cells with no
      nuclear foci. No nuclear signals were detected in all controls examined (n = 6)
      and in 1 DM1-positive sample with a CTG expansion <100 copies. CONCLUSION:
      Nuclear foci, and therefore the DM1 mutation they are caused by, can be detected
      efficiently on interphase nuclei of trophoblast cells with RNA-FISH when the CTG
      expansion is >200 copies.

PMID- 16449217
TI  - Point-of-care i-STAT cardiac troponin I for assessment of patients with symptoms
      suggestive of acute coronary syndrome.
AB  - BACKGROUND: Few studies have investigated the role of cardiac troponin point-of
      care (POC) testing for predicting adverse outcomes in acute coronary syndrome
      (ACS) patients. We investigated the use of a POC cTnI assay in ACS patients.
      METHODS: We studied consecutive patients (n = 367) presenting with symptoms
      suggestive of ACS who were admitted through the emergency department. We measured
      plasma cTnI with the i-STAT assay. Patients were risk-stratified based on cTnI
      concentrations defined by the predetermined 99th percentile reference limit for
      plasma (0.04 microg/L). Patients were followed for 60 days. We computed survival
      and event curves with the Kaplan-Meier method and compared risk stratification
      groups with the log-rank test. RESULTS: Acute myocardial infarction (MI) was
      diagnosed in 8.1% of patients. Odds ratios and 95% confidence intervals for all
      cause death (ACD), MI or ACD, MI or cardiac death, and cardiac death at 60 days
      were all statistically significant after adjustment for age, diabetes,
      hypertension, and history of renal failure as follows: 2.54 (1.24-5.20), P =
      0.009; 2.76 (1.37-5.58), P = 0.003; 5.98 (1.65-21.7), P = 0.008; and 2.54 (1.24
      5.20), P = 0.009. Kaplan-Meier curves showed early separation between patients
      with increased vs. reference concentrations before 30 days for ACD, MI or ACD,
      and MI or cardiac death. CONCLUSION: The i-STAT POC cTnI assay can be added to
      the list of assays for risk stratification.

PMID- 16449218
TI  - Prediction of hospital mortality rates by admission laboratory tests.
AB  - BACKGROUND: The aim of this study was to explore whether electronically retrieved
      laboratory data can predict mortality in internal medicine departments in a
      regional hospital. METHODS: All 10,308 patients hospitalized in internal medicine
      departments over a 1-year period were included in the cohort. Nearly all patients
      had a complete blood count and basic clinical chemistries on admission. We used
      logistic regression analysis to predict the 573 deaths (5.6%), including all
      variables that added significantly to the model. RESULTS: Eight laboratory
      variables and age significantly and independently contributed to a logistic
      regression model (area under the ROC curve, 88.7%). The odds ratio for the final
      model per quartile of risk was 6.44 (95% confidence interval, 5.42-7.64), whereas
      for age alone, the odds ratio per quartile was 2.01 (95% confidence interval,
      1.84-2.19). CONCLUSIONS: A logistic regression model including only age and
      electronically retrieved laboratory data highly predicted mortality in internal
      medicine departments in a regional hospital, suggesting that age and routine
      admission laboratory tests might be used to ensure a fair comparison when using
      mortality monitoring for hospital quality control.

PMID- 16449219
TI  - Should we really determine a reference population for the definition of thyroid
      stimulating hormone reference interval?

PMID- 16449220
TI  - Serum creatinine values in elite athletes competing in 8 different sports:
      comparison with sedentary people.

PMID- 16449221
TI  - Nanotechnologic nutraceuticals: nurturing or nefarious?

PMID- 16449222
TI  - Effect of sample collection tubes on cerebrospinal fluid concentrations of tau
      proteins and amyloid beta peptides.

PMID- 16449223
TI  - Microwave-assisted derivatization of glucose and galactose for gas
      chromatographic determination in human plasma.

PMID- 16449224
TI  - Indirect methods for reference intervals based on current data.

PMID- 16449226
TI  - Inappropriate reference intervals for carboxyhemoglobin at some Florida
      hospitals.

PMID- 16449227
TI  - Endogenous lipid hydroperoxide-mediated DNA-adduct formation in min mice.
AB  - Despite intensive research over the last two decades, there are still no specific
      markers of endogenous lipid hydroperoxide-mediated DNA damage. We recently
      demonstrated that heptanone-etheno-2'-deoxyguanosine adducts are formed in the
      DNA of rat intestinal epithelial cells that stably express cyclooxygenase-2.
      Heptanone-etheno adducts can only arise from the reaction of lipid hydroperoxide
      derived 4-oxo-2(E)-nonenal with DNA. This raised the possibility that similar
      adducts would be formed in vivo in settings where cyclooxygenase-2 expression is
      increased. Therefore, DNA-adduct formation was studied in C57BL/6JAPC(min) mice,
      a colorectal cancer mouse model in which cyclooxygenase-2 is up-regulated. 15(S)
      Hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid is the major lipid hydroperoxide
      produced endogenously by cyclooxygenase-2. It undergoes homolytic decomposition
      to the DNA-reactive bifunctional electrophile 4-oxo-2(E)-nonenal, which forms
      heptanone-etheno adducts with DNA. A quantitative comparison was made of the
      heptanone-etheno-DNA adducts present in C57BL/6J and C57BL/6JAPC(min) mice. Using
      highly specific and sensitive methodology based on stable isotope dilution liquid
      chromatography/tandem mass spectrometry, we have detected the endogenous
      formation of heptanone-etheno adducts in mammalian tissue DNA for the first time.
      In addition, we found that there were statistically significant increased levels
      of the heptanone-etheno-2'-deoxyguanosine and heptanone-etheno-2'-deoxycytidine
      adducts in the C57BL/6JAPC(min) mice when compared with the control C57BL/6J
      mice.

PMID- 16449228
TI  - Regulation of lipid metabolism genes, lipid carrier protein lipophorin, and its
      receptor during immune challenge in the mosquito Aedes aegypti.
AB  - In the mosquito Aedes aegypti, the expression of two fat body genes involved in
      lipid metabolism, a lipid carrier protein lipophorin (Lp) and its lipophorin
      receptor (LpRfb), was significantly increased after infections with Gram (+)
      bacteria and fungi, but not with Gram (-) bacteria. The expression of these genes
      was enhanced after the infection with Plasmodium gallinaceum. RNA interference
      (RNAi) knockdown of Lp strongly restricted the development of Plasmodium oocysts,
      reducing their number by 90%. In Vg-DeltaREL1-A transgenic mosquitoes, with gain
      of-function phenotype of Toll/REL1 immune pathway activated after blood feeding,
      both the Lp and LpRfb genes were overexpressed independently of septic injury.
      The same phenotype was observed in the mosquitoes with RNAi knockdown of Cactus,
      an IkappaB inhibitor in the Toll/REL1 pathway. These results showed that, in the
      mosquito fat body, both Lp and LpRfb gene expression were regulated by the
      Toll/REL1 pathway during immune induction by pathogen and parasite infections.
      Indeed, the proximal region of the LpRfb promoter contained closely linked
      binding motifs for GATA and NF-kappaB transcription factors. Transfection and in
      vivo RNAi knockdown experiments showed that the bindings of both GATA and NF
      kappaB transcription factors to the corresponding motif were required for the
      induction of the LpRfb gene. These findings suggest that lipid metabolism is
      involved in the mosquito systemic immune responses to pathogens and parasites.

PMID- 16449230
TI  - Asparagine 706 and glutamate 183 at the catalytic site of sarcoplasmic reticulum
      Ca2+-ATPase play critical but distinct roles in E2 states.
AB  - Mutants with alteration to Asn(706) of the highly conserved (701)TGDGVND(707)
      motif in domain P of sarcoplasmic reticulum Ca(2+)-ATPase were analyzed for
      changes in transport cycle kinetics and binding of the inhibitors vanadate, BeF,
      AlF, and MgF. The fluorides likely mimic the phosphoryl group/P(i) in the
      respective ground, transition, and product states of phosphoenzyme hydrolysis
      (Danko, S., Yamasaki, K., Daiho, T., and Suzuki, H. (2004) J. Biol. Chem. 279,
      14991-14998). Binding of BeF, AlF, and MgF was also studied for mutant Glu(183) -
      > Ala, where the glutamate of the (181)TGES(184) motif in domain A is replaced.
      Mutations of Asn(706) and Glu(183) have in common that they dramatically impede
      the function of the enzyme in E2 states, but have little effect in E1. Contrary
      to the Glu(183) mutant, in which E2P slowly accumulates (Clausen, J. D., Vilsen,
      B., McIntosh, D. B., Einholm, A. P., and Andersen, J. P. (2004) Proc. Natl. Acad.
      Sci. U. S. A. 101, 2776-2781), E2P formation was not detectable with the Asn(706)
      mutants. Differential sensitivities of the mutants to inhibition by AlF, MgF, and
      BeF made it possible to distinguish different roles of Asn(706) and Glu(183).
      Hence, Asn(706) is less important than Glu(183) for gaining the transition state
      during E2P hydrolysis but plays critical roles in stabilization of E2P ground and
      E2.P(i) product states and in the major conformational changes associated with
      the Ca(2)E1P --> E2P and E2 --> Ca(2)E1 transitions, which seem to be facilitated
      by interaction of Asn(706) with domain A.

PMID- 16449229
TI  - Members of the Arabidopsis FAE1-like 3-ketoacyl-CoA synthase gene family
      substitute for the Elop proteins of Saccharomyces cerevisiae.
AB  - Several 3-keto-synthases have been studied, including the soluble fatty acid
      synthases, those involved in polyketide synthesis, and the FAE1-like 3-ketoacyl
      CoA synthases. All of these condensing enzymes have a common ancestor and an
      enzymatic mechanism that involves a catalytic triad consisting of Cys, His, and
      His/Asn. In contrast to the FAE1-like family of enzymes that mediate plant
      microsomal fatty acid elongation, the condensation step of elongation in animals
      and in fungi appears to be mediated by the Elop homologs. Curiously these
      proteins bear no resemblance to the well characterized 3-keto-synthases. There
      are three ELO genes in yeast that encode the homologous Elo1p, Elo2p, and Elo3p
      proteins. Elo2p and Elo3p are required for synthesis of the very long-chain fatty
      acids, and mutants lacking both Elo2p and Elo3p are inviable confirming that the
      very long-chain fatty acids are essential for cellular functions. In this study
      we show that heterologous expression of several Arabidopsis FAE1-like genes
      rescues the lethality of an elo2Deltaelo3Delta yeast mutant. We further
      demonstrate that FAE1 acts in conjunction with the 3-keto and trans-2,3-enoyl
      reductases of the elongase system. These studies indicate that even though the
      plant-specific FAE1 family of condensing enzymes evolved independently of the
      Elop family of condensing enzymes, they utilize the same reductases and
      presumably dehydratase that the Elop proteins rely upon.

PMID- 16449232
TI  - Autophagy is not a main contributor to the degradation of phospholipids in
      tobacco cells cultured under sucrose starvation conditions.
AB  - Net degradation of cellular components occurs in plant cells cultured under
      starvation conditions, and autophagy contributes to the degradation of
      intracellular proteins. In this study, we investigated the degradation of
      membrane phospholipids by autophagy in cultured tobacco (Nicotiana tabacum)
      cells. The amounts of total phospholipids and a major phospholipid,
      phosphatidylcholine (PC), decreased, whereas phosphorylcholine, a degradation
      product of PC, increased in response to deprivation of sucrose. The addition of
      glycerol to the culture medium inhibited both the degradation of phospholipids
      and the concomitant increase of phosphorylcholine. Glycerol, however, did not
      block autophagy, which was assessed by the accumulation of autolysosomes in the
      presence of a cysteine protease inhibitor. On the other hand, 3-methyladenine, an
      inhibitor of autophagy, did not affect the net degradation of PC. We labeled
      intracellular phospholipids by loading cells with a fluorochrome-labeled fatty
      acid and chased it under sucrose-free conditions. Glycerol slowed down the
      decrease in the amount of fluorochrome-labeled PC, suggesting that it inhibits
      the degradation process of PC. These results show that phospholipids are degraded
      by mechanisms different from autophagy in tobacco cells cultured under sucrose
      free conditions.

PMID- 16449231
TI  - Characterization of the vernalization response in Lolium perenne by a cDNA
      microarray approach.
AB  - Many plant species including temperate grasses require vernalization in order to
      flower. Vernalization is the process of promotion of flowering after exposure to
      prolonged periods of cold. To investigate the vernalization response in monocots,
      the expression patterns of about 1,500 unique genes of Lolium perenne were
      analyzed by a cDNA microarray approach, at different time points after transfer
      of plants to low temperatures. Vernalization of L. perenne takes around 80 d and,
      therefore, the plants were incubated at low temperatures for at least 12 weeks. A
      total of 70 cold-responsive genes were identified that are either up- or down
      regulated with a minimal 2-fold difference compared with the common reference.
      The majority of these genes show a very rapid response to the cold treatment,
      indicating that their expression is affected by the cold stress and, therefore,
      these genes are not likely to be involved in the flowering process. Based on
      hierarchical clustering, one gene could be identified that is down-regulated
      towards the end of the cold period and, in addition, a few genes have been found
      that are up-regulated in the last weeks of the cold treatment and, hence, are
      putative candidates for genes involved in the vernalization response. Three of
      the up-regulated genes are homologous to members of the MADS box, CONSTANS-like
      and JUMONJI families of transcription factors, respectively. The latter two are
      novel genes not connected previously to vernalization-induced flowering.
      Furthermore, members of the JUMONJI family of transcription factors have been
      shown to be involved in chromatin remodeling, suggesting that this molecular
      mechanism, as in Arabidopsis, plays a role in the regulation of the vernalization
      response in monocots.

PMID- 16449233
TI  - Compensation for PSII photoinactivation by regulated non-photochemical
      dissipation influences the impact of photoinactivation on electron transport and
      CO2 assimilation.
AB  - The extent to which PSII photoinactivation affects electron transport (PhiPSII)
      and CO2 assimilation remains controversial, in part because it frequently occurs
      alongside inactivation of other components of photosynthesis, such as PSI. By
      manipulating conditions (darkness versus low light) after a high light/low
      temperature treatment, we examined the influence of different levels of PSII
      inactivation at the same level of PSI inactivation on PhiPSII and CO2
      assimilation for Arabidopsis. Furthermore, we compared PhiPSII at high light and
      optimum temperature for wild-type Arabidopsis and a mutant (npq4-1) with impaired
      capacities for energy dissipation. Levels of PSII inactivation typical of natural
      conditions (< 50%) were not associated with decreases in PhiPSII and CO2
      assimilation at photon flux densities (PFDs) above 150 micromol m(-2) s(-1). At
      higher PFDs, the light energy being absorbed was in excess of the energy that
      could be utilized by downstream processes. Arabidopsis plants downregulate PSII
      activity to dissipate such excess in accordance with the level of PSII
      photoinactivation that also serves to dissipate absorbed energy. Therefore, the
      overall levels of non-photochemical dissipation and the efficiency of
      photochemistry were not affected by PSII inactivation at high PFD. Under low PFD
      conditions, such compensation is not necessary, because the amount of light
      energy absorbed is not in excess of that needed for photochemistry, and inactive
      PSII complexes are dissipating energy. We conclude that moderate
      photoinactivation of PSII complexes will only affect plant performance when
      periods of high PFD are followed by periods of low PFD.

PMID- 16449235
TI  - Impaired helix 12 dynamics due to proline 892 substitutions in the androgen
      receptor are associated with complete androgen insensitivity.
AB  - Structural studies of the ligand-binding domain (LBD) of several steroid
      receptors have revealed that the dynamic properties of the C-terminal helix 12
      (H12) are the major determinant of the activation mode of these receptors. H12
      exhibits high mobility and different conformations in the absence of ligand. Upon
      ligand binding, H12 is stabilized in a precise position to seal the ligand
      binding pocket and finalize the assembly of the activation function (AF-2)
      domain. In this study, we investigated the role of the conserved proline 892 of
      the androgen receptor (AR) in directing the dynamic location and orientation of
      the AR-H12. We used a combined approach including kinetic and biochemical assays
      with molecular dynamic simulations to analyze two substitutions (P892A and P892L)
      identified in individuals with complete androgen insensitivity syndrome. Our
      analyses revealed distinct mechanisms by which these substitutions impair H12
      function resulting in severely defective receptors. The AR-P892A receptor
      exhibited reduced ligand binding and transactivational potential because of an
      increased flexibility in H12. The AR-P892L substitution renders the receptor
      inactive due to a distorted, unstructured and misplaced H12. To confirm the
      mutants' inability to stabilize H12 in an active position, we have developed a
      novel in vivo assay to evaluate the accessibility of the H12-docking site on the
      AR-LBD surface. An extrinsic AR-H12 peptide was able to interact with wild-type
      and mutant LBDs in the absence of ligand. Ligand-induced proper positioning of
      the intrinsic H12 of wild-type AR prevented these interactions, whereas the
      misplacement of the mutants' H12 did not. Proline at this position may be
      critical for H12 dynamics not only in the AR, but also in other nuclear receptors
      where this proline is conserved.

PMID- 16449234
TI  - Acute effects of fentanyl on breathing pattern in anaesthetized subjects.
AB  - BACKGROUND: The predominant effect of opioids on respiratory pattern during
      anaesthesia is an increase in the duration of expiration (an effect on 'timing'),
      but there may also be changes in tidal volume (an effect on 'drive'). Timing and
      drive are controlled by separate neuronal systems, but are infrequently
      considered individually. The effects of opioids on breathing are not well
      characterized clinically because changes in carbon dioxide and anaesthetic levels
      usually occur at the same time, and can obscure the effects of the opioid.
      METHODS: To study these effects in isolation, we established stable mild
      hypercapnia in female patients breathing spontaneously during sevoflurane
      anaesthesia, and then gave fentanyl 0.5 microg kg(-1) i.v. End-tidal carbon
      dioxide and sevoflurane concentrations were maintained constant, and the changes
      in timing of inspiration, expiration and tidal volume were measured. RESULTS: The
      duration of inspiration increased by 30%, and the duration of expiration
      increased by 95%. Tidal volume increased in proportion to inspiratory duration,
      and the pattern of flow during the breath was recognizably changed, with a
      reduction in the rate of increase of flow at the onset of inspiration.
      CONCLUSIONS: Small doses of opioid given when anaesthesia and carbon dioxide are
      stable affect respiratory timing predominantly, but in addition changes in the
      pattern of motor output can be detected.

PMID- 16449236
TI  - Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1
      gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis.
AB  - Axenfeld-Rieger ocular dysgenesis is associated with mutations of the human PITX2
      and FOXC1 genes, which encode transcription factors of the homeodomain and
      forkhead types, respectively. We have identified a functional link between FOXC1
      and PITX2 which we propose underpins the similar Axenfeld-Rieger phenotype caused
      by mutations of these genes. FOXC1 and PITX2A physically interact, and this
      interaction requires crucial functional domains on both proteins: the C-terminal
      activation domain of FOXC1 and the homeodomain of PITX2. Immunofluorescence
      further shows PITX2A and FOXC1 to be colocalized within a common nuclear
      subcompartment. Furthermore, PITX2A can function as a negative regulator of FOXC1
      transactivity. This work ties both proteins into a common pathway and offers an
      explanation of why increased FOXC1 gene dosage produces a phenotype resembling
      that of PITX2 deletions and mutations. Ocular phenotypes arise despite the
      deregulated expression of FOXC1-target genes through mutations in FOXC1 or PITX2.
      Ultimately, PITX2 loss of function mutations have a compound effect: the reduced
      expression of PITX2-target genes coupled with the extensive activation of FOXC1
      regulated targets. Our findings indicate that the functional interaction between
      FOXC1 and PITX2A underlies the sensitivity to FOXC1 gene dosage in Axenfeld
      Rieger syndrome and related anterior segment dysgeneses.

PMID- 16449237
TI  - Parkin enhances mitochondrial biogenesis in proliferating cells.
AB  - We describe a novel function of parkin, a RING protein, which is elaborately
      involved in mitochondrial biogenesis. Parkin was located within the mitochondrial
      organelle of proliferating cells. Anti-proliferative treatments released parkin
      from mitochondria to cytosol. Results of pharmacological treatments indicate that
      parkin was released from mitochondria when permeability transition pore was
      opened. The extra-mitochondrial localization was also observed in differentiated
      cells. In proliferating cells, transcription and replication of mitochondrial DNA
      was enhanced by parkin overexpression and attenuated by parkin suppression with
      siRNA. Parkin was associated with mitochondrial transcription factor A (TFAM) and
      enhanced TFAM-mediated mitochondrial transcription. These results indicate that
      parkin is involved in the regulation of mitochondrial transcription/replication
      other than the ubiquitin-mediated protein degradation system in proliferating
      cells.

PMID- 16449238
TI  - Generation of trans-mitochondrial mice carrying homoplasmic mtDNAs with a
      missense mutation in a structural gene using ES cells.
AB  - Generation of various kinds of trans-mitochondrial mice, mito-mice, each carrying
      mtDNAs with a different pathogenic mutation, is required for precise
      investigation of the pathogenesis of mitochondrial diseases. This study used two
      respiration-deficient mouse cell lines as donors of mtDNAs with possible
      pathogenic mutations. One cell line expressed 45-50% respiratory activity due to
      mouse mtDNAs with a T6589C missense mutation in the COI gene (T6589C mtDNA) and
      the other expressed 40% respiratory activity due to rat (Rattus norvegicus)
      mtDNAs in mouse cells. By cytoplasmic transfer of these mtDNAs to mouse ES cells,
      we isolated respiration-deficient ES cells. We obtained chimeric mice and
      generated their F(6) progeny carrying mouse T6589C mtDNAs by its female germ line
      transmission. They were respiration-deficient and thus could be used as models of
      mitochondrial diseases caused by point mutations in mtDNA structural genes.
      However, chimeric mice and mito-mice carrying rat mtDNAs were not obtained,
      suggesting that significant respiration defects or some deficits induced by rat
      mtDNAs in mouse ES cells prevented their differentiation to generate mice
      carrying rat mtDNAs.

PMID- 16449239
TI  - Crossover frequency and synaptonemal complex length: their variability and
      effects on human male meiosis.
AB  - In this study, immunocytogenetics has been used in combination with the
      subtelomere-specific multiplex-fluorescent in-situ hybridization (stM-FISH) assay
      to identify 4681 autosomal synaptonemal complexes (SCs) of two fertile men.
      Comparisons of crossover maps for each individual SC between two men with
      extremely different meiotic crossover frequencies show that a low crossover
      frequency results in (i) a higher frequency of XY pairs and of small SCs without
      MLH1 foci and (ii) lower frequency of crossovers in the proximity of centromeres.
      In both cases, the bivalents which most frequently lacked MLH1 foci were the XY
      pair and the SC21. Analysis of SC length showed that SC arms can be longer or
      shorter than the corresponding mitotic one. Moreover, for a given SC, the
      variation in length found in one arm was independent of the variation observed in
      the other one (e.g. SC1p arms are longer than SC1q arms). The results confirmed
      that reduction in the crossover frequency may increase the risk of achiasmate
      small bivalents and that interindividual differences in crossover frequency could
      explain the variability in the frequencies of aneuploidy in human sperm. How MLH1
      foci are positioned within the SC is discussed based on detailed MLH1 foci
      distributions and interfoci distances. Finally, evidence that the variation of
      the SC arm length may reflect the abundance of open and of compact chromatin
      fibers in the arm is shown.

PMID- 16449240
TI  - A Phase I study of escalating doses of the tyrosine kinase inhibitor semaxanib
      (SU5416) in combination with irinotecan in patients with advanced colorectal
      carcinoma.
AB  - BACKGROUND: One of the most studied pro-angiogenic factors involved in the
      development of colorectal cancer is the vascular endothelial growth factor
      (VEGF). The small molecule tyrosine kinase inhibitor semaxanib (SU5416) is one of
      the several agents targeting the VEGF signaling pathway, and its development
      centered mostly in the treatment of colorectal cancer. METHODS: We designed and
      conducted an NCI-sponsored trial to determine the maximum tolerated dose (MTD)
      and dose-limiting toxicities (DLTs) of semaxanib given twice weekly in
      combination with weekly irinotecan in patients with advanced colorectal cancer
      who had failed at least one prior treatment. The irinotecan dose was fixed at 125
      mg/m(2) given weekly for 4 weeks followed by 2 weeks of rest. Patients with prior
      pelvic irradiation received a reduced dose of 100 mg/m(2). The semaxanib dose was
      escalated, going from 85 to 110 mg/m(2) and finally to 145 mg/m(2). RESULTS: Ten
      patients were treated in our study and all were evaluable for toxicity. There
      were no drug-related Grade 4 toxicities. There was one episode of Grade 3
      headache and one episode of Grade 3 vomiting. The most common Grades 1 and 2
      toxicities included diarrhea, abdominal cramping, anemia and nausea. Nine
      patients completed at least one 6 week cycle of treatment and were considered
      evaluable for response. Among those nine, two had a partial response, three had
      stable disease and four had progressive disease after the first cycle.
      CONCLUSIONS: Both irinotecan and semaxanib could be given at their full single
      agent recommended doses without significant toxicity, and the combination showed
      signs of clinical activity. However, owing to discouraging results from Phase III
      trials, it is unlikely that this combination will be further explored.

PMID- 16449241
TI  - A correlation between EGFR gene mutation status and bronchioloalveolar carcinoma
      features in Japanese patients with adenocarcinoma.
AB  - BACKGROUND: The presence of epidermal growth factor receptor (EGFR) mutations in
      gefitinib-naive lung cancer patients has been reported to be higher in females,
      in non-smokers, in Japanese, and in adenocarcinoma patients, especially in
      bronchioloalveolar carcinoma (BAC). To further investigate the prevalence of EGFR
      mutations in relation to pathological factors, we evaluated EGFR mutations in
      series of Japanese adenocarcinoma patients who had never been treated with
      gefitinib. METHODS: In the previous studies, we examined mutation status in the
      tyrosine kinase domain of EGFR, exon18 through exon21, in 112 primary lung
      adenocarcinoma samples. Using these data, adenocarcinomas were histologically
      classified according to the presence or absence of bronchioloalveolar components.
      RESULTS: Among 112 patients, 48 had adenocarcinoma with BAC components. Those
      with adenocarcinomas with BAC components had higher frequency of EGFR mutation
      (28/48, 58%) than those with non-BAC adenocarcinoma (24/64, 37%, P = 0.036). Male
      patients had the same trend; 12/23 (52%) male patients with adenocarcinoma with
      BAC components and 10/47 (21%) of those with non-BAC adenocarcinoma had EGFR
      mutation (P = 0.0135) but there was no correlation between the EGFR mutation
      status and with/without BAC components in 42 female patients (P = 0.30). Among 11
      male non-smokers, patients with adenocarcinoma with BAC components had a tendency
      to have EGFR mutation more frequently than those with non-BAC adenocarcinoma (P =
      0.061). In clear contrast, the frequency of EGFR mutation did not differ
      significantly between male smoker patients with adenocarcinoma with BAC
      components and those with non-BAC. Among patients with adenocarcinoma with BAC
      components, those with adenocarcinoma with EGFR gene mutation had a significantly
      better 5 year survival than those with adenocarcinoma with wild-type (85.7 versus
      46.0%, P = 0.0017). CONCLUSIONS: Adenocarcinomas with BAC components in male non
      smokers seem to predict the presence of EGFR mutation. Half of female
      adenocarcinoma patients with EGFR mutation exhibit adenocarcinomas with non-BAC
      suggesting a different behavior from those in males. The prognosis of patients
      with adenocarcinoma with BAC components with EGFR gene mutation is predicted to
      be better than that of patients with adenocarcinoma with BAC components with wild
      type EGFR gene.

PMID- 16449242
TI  - General practitioners may diagnose type 2 diabetes mellitus at an early disease
      stage in patients they know well.
AB  - BACKGROUND: Continuity of care may not only save time and money for the health
      care system, but may also be beneficial for the individual patient. How well GPs
      know their patients may potentially lead to an early diagnosis of a slowly
      progressive chronic disease like type 2 diabetes mellitus (T2DM). The aim of this
      paper is to investigate this hypothesis. METHODS: A cross-sectional, population
      based study of 1136 patients newly diagnosed with T2DM by their GP. Our main
      outcomes were how well the GPs' knew their patients (questionnaire) and
      centralized analysis of glycosylated haemoglobin A(1c). Multivariate linear
      regression models were used to allow adjustment for confounding variables.
      RESULTS: GPs classified how well they knew their patients as being not well for
      13.5% (153/1136) of their patients, as fairly well for 38.6% (438/1136) and as
      very well for 48.0% (545/1136). Patients whom the GPs classified as not knowing
      well had relatively high glycaemic levels compared with levels among other
      patients, a finding that was confirmed in multivariate linear regression models.
      CONCLUSIONS: Our data show that the glycaemic level among patients whom the GP
      characterize as knowing well or fairly well is relatively low compared with among
      patients whom the GP characterize as not knowing well. We suggest that this
      reflects a late diagnosis in these patients, and that GPs should be especially
      aware of undiagnosed T2DM among patients whom they do not know well.

PMID- 16449244
TI  - Atrial pathology in cardiac amyloidosis: evidence from ECG and cardiovascular
      magnetic resonance.

PMID- 16449243
TI  - Dysphagia associated with an aneurysm decades after Blalock-Taussig anastomosis.

PMID- 16449245
TI  - Noise burden and the risk of myocardial infarction: false interpretation of
      results due to inadequate treatment of data.

PMID- 16449246
TI  - Who needs a heart transplant?

PMID- 16449247
TI  - Prognosis in atrial fibrillation.

PMID- 16449248
TI  - Zotarolimus-eluting stents reduce experimental coronary artery neointimal
      hyperplasia after 4 weeks.
AB  - AIMS: The addition of drug elution to coronary stents plays an integral role in
      coronary restenosis prevention. The present study was undertaken to determine the
      mechanism of action and the in vitro and in vivo efficacy of zotarolimus, a new
      chemical entity designed specifically for elution from phosphorylcholine (PC)
      coated stents, for the reduction of neointimal hyperplasia in porcine coronary
      arteries. METHODS AND RESULTS: In vitro studies of Zotarolimus bound to FKBP-12
      potently inhibited smooth muscle cells (SMCs) and endothelial cell (EC)
      proliferation. Twenty PC-only and 20 stents eluting zotarolimus 10 microg/mm were
      implanted in the coronary arteries of 20 domestic juvenile swine. After 28 days,
      zotarolimus stents exhibited less area stenosis (22.4+/-8.6 vs. 35.7+/-13%, P =
      0.01), less neointimal area (1.69+/-0.55 vs. 2.78+/-1.07 mm(2), P = 0.01), less
      neointimal thickness (0.25+/-0.07 vs. 0.38+/-0.13 mm, P = 0.01), and greater
      lumen area (6.07+/-1.39 vs. 5.02+/-1.3 mm2, P = 0.01). All arteries in both the
      polymer-only and polymer/drug stent showed near-complete healing and minimal
      toxicity. Zotarolimus did not affect the extrastent segments nor alter the
      overall artery size (external elastic lamina cross-sectional area 9.18+/-1.19 vs.
      9.06+/-1.28 mm2, P = 0.7). CONCLUSION: Zotarolimus binds to FKBP-12 and in vitro
      inhibits SMC and EC proliferation. Zotarolimus applied to PC-coated stents
      reduces neointima in the swine coronary model after 28 days. These results
      suggest potentially promising human clinical application for coronary stenting
      with this polymer/drug combination.

PMID- 16449249
TI  - Clinical vignette. Multiple pulmonary arteriovenous fistulas in hereditary
      haemorrhagic teleangiectasia.

PMID- 16449251
TI  - Each lipase has a unique sensitivity profile for organophosphorus inhibitors.
AB  - Lipases sensitive to organophosphorus (OP) inhibitors play critical roles in cell
      regulation, nutrition, and disease, but little is known on the toxicological
      aspects in mammals. To help fill this gap, six lipases or lipase-like proteins
      are assayed for OP sensitivity in vitro under standard conditions (25 degrees C,
      15 min incubation). Postheparin serum lipase, lipoprotein lipase (LPL) (two
      sources), pancreatic lipase, monoacylglycerol (MAG) lipase, cholesterol esterase,
      and KIAA1363 are considered with 32 OP pesticides and related compounds.
      Postheparin lipolytic activity in rat serum is inhibited by 14 OPs, including
      chlorpyrifos oxon (IC50 50-97 nM). LPL (bovine milk and Pseudomonas) generally is
      less inhibited by the insecticides or activated oxons, but the milk enzyme is
      very sensitive to six fluorophosphonates and benzodioxaphosphorin oxides (IC50 7
      20 nM). Porcine pancreatic lipase is very sensitive to dioctyl 4-nitrophenyl
      phosphate (IC50 8 nM), MAG lipase of mouse brain to O-4-nitrophenyl
      methyldodecylphosphinate (IC50 0.6 nM), and cholesterol esterase (bovine
      pancreas) to all of the classes of OPs tested (IC50 < 10 nM for 17 compounds).
      KIAA1363 is sensitive to numerous OPs, including two O-4-nitrophenyl compounds
      (IC50 3-4 nM). In an overview, inhibition of 28 serine hydrolases (including
      lipases) by eight OPs (chlorpyrifos oxon, diazoxon, paraoxon, dichlorvos, and
      four nonpesticides) showed that brain acetylcholinesterase is usually less
      sensitive than butyrylcholinesterase, liver esterase, cholesterol esterase, and
      KIAA1363. In general, each lipase (like each serine hydrolase) has a different
      spectrum of OP sensitivity, and individual OPs have unique ranking of potency for
      inhibition of serine hydrolases.

PMID- 16449252
TI  - Comparative pulmonary toxicological assessment of oil combustion particles
      following inhalation or instillation exposure.
AB  - Controversy persists regarding the validity of intratracheal instillation (IT) of
      particulate matter (PM) as a surrogate for inhalation exposure (IH) in rodents.
      Concerns center on dose, dose-rate, and distribution of material within the lung.
      Acute toxicity of a residual oil fly ash (ROFA) administered by IH was compared
      to those effects of a single IT bolus at an IH-equivalent dose. Male Sprague
      Dawley rats (60 days old) were exposed by nose-only IH to approximately 12 mg/m3
      for 6 h. Inter-lobar dose distribution of ROFA, dissected immediately post
      exposure, was assayed by neutron activation. Vanadium and nickel were used as
      ROFA markers. IT administration of the IH-equivalent dose (110 microg) showed
      similar (<15%) interlobular distribution, with the exception of the inferior lobe
      dose (IT>IH approximately 25%). Evaluation of airway hyperreactivity (AHR),
      bronchoalveolar lavage fluid (BALF) constituents, and histopathology was
      conducted at 24, 48, and 96 h post exposure. AHR in the IH group was minimally (p
      > 0.05) affected by treatment, but was significantly increased ( approximately
      40%) at both 24 and 48 h post IT. Inflammation in both groups, as measured by
      alterations in BALF protein, lactate dehydrogenase and neutrophils, was virtually
      identical at all time points. Alveolitis and bronchial inflammation/epithelial
      hypertrophy were prominent 24 h following IT, but not apparent after IH.
      Conversely, alveolar hemorrhage, congestion, and airway exudate were pronounced
      at 48 h post-IH but not remarkable in the IT group. Thus, IT-ROFA mimicked IH in
      terms of lobar distribution and injury biomarkers over 96 h, while morphological
      alterations and AHR appeared to be more dependent on the method of
      administration.

PMID- 16449253
TI  - Beta-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or
      misclassification?
AB  - BACKGROUND: In adults, a fraction of diabetic individuals with beta-cell
      autoantibodies has initially non-insulin requiring diabetes clinically appearing
      as type 2 diabetes mellitus (T2DM), named latent autoimmune diabetes in adulthood
      (LADA). The occurrence of beta-cell autoantibodies in European children and
      adolescents with T2DM has not been reported so far. METHODS: The frequency of
      beta-cell autoantibodies (anti-GAD, anti-IA-2, and anti-ICA) was determined in
      7050 diabetic children and adolescents. The type of diabetes was classified by
      paediatric diabetic specialists based on the clinical presentation. Children with
      non-insulin dependent T2DM over a one year period were studied separately.
      RESULTS: A total of 6922 children were clinically classified as having type 1
      diabetes (T1DM) and 128 children as having T2DM. Thirty six per cent of the
      children with T2DM had at least one detectable beta-cell autoantibody. These
      children did not differ significantly from the children with T2DM and without
      autoantibodies in respect of age, gender, weight status, lipids, blood pressure,
      C-peptide, glucose, and HbA1c at manifestation, as well as frequency of anti
      thyroidal antibodies and insulin treatment during follow up. In the subgroup of
      the 38 children with T2DM without insulin requirement over a one year period,
      autoantibodies occurred in 32%. These 12 children were predominantly obese (67%),
      female (67%), and in the pubertal age range. CONCLUSION: beta-cell autoantibodies
      were detectable in a subgroup of initially non-insulin dependent diabetic
      children and adolescents with the clinical appearance of T2DM. Following the
      terminology "latent autoimmune diabetes in adulthood (LADA)", this subgroup might
      be classified as "LADY" (latent autoimmune diabetes in youth).

PMID- 16449254
TI  - Patterns of disease in Sri Lankan dengue patients.
AB  - BACKGROUND: Dengue is the most important mosquito borne viral infection in the
      world. Nearly 90% of infections occur in children. At present, prospective
      information on clinical and laboratory findings in South Asian children with
      dengue is generally lacking. AIM: To describe patterns of clinical disease in a
      cohort of children hospitalised with dengue during a major dengue epidemic in Sri
      Lanka. RESULTS: A total of 104 children were studied during a three month period.
      Eighteen had dengue fever (DF) and 86 had dengue haemorrhagic fever (DHF). Of
      those with DHF, 34, 23, 27, and 2 had DHF grade I, II, III, and IV respectively.
      Based on dengue serology testing, 13 of the DF patients had a primary infection
      and 5 had secondary dengue infections. In contrast, 68 of the children with DHF
      had secondary and 18 had primary dengue infections. Oral candidiasis was seen in
      19 children. The odds ratio for children with secondary dengue infection to
      develop DHF was 9.8 (95% CI 3.1 to 31.2). CONCLUSION: Studies on patterns of
      paediatric dengue disease in different regions should help clinicians and health
      administrators make more informed and evidence based health planning decisions.
      It should also help towards mapping out dengue trends on a global scale. Oral
      candidiasis has not been previously documented in children suffering with acute
      dengue in Sri Lanka or elsewhere. Studying underlying reasons for this
      manifestation during future dengue epidemics may provide useful leads in
      understanding overall dengue pathogenesis.

PMID- 16449255
TI  - Computed tomography in children with cystic fibrosis: a new way to reduce
      radiation dose.
AB  - AIMS: To determine whether the monitoring of respiratory disease progression in
      children with cystic fibrosis (CF) can be made using six pre-selected computed
      tomography (CT) cuts in lieu of the conventional full study. METHODS: Forty one
      lung CT scans from 21 paediatric patients with CF were analysed. The Bhalla and
      Nathanson scores of the total lung CT and the six pre-selected CT cuts were
      compared. RESULTS: The Bhalla mean score of the total lung CT evaluated by two
      radiologists was 5.62. It was 5.36 when just the six pre-selected sections were
      evaluated. The difference between means was not statistically significant. The
      Nathanson mean score of the total lung CT evaluated by both radiologists was
      66.11; it was 66.51 when just the six pre-selected sections were evaluated. The
      difference between means was not statistically significant. The mean total
      radiation dose from a single whole lung CT scan was 716.22 mGy.cm. A dose of
      250.66 mGy.cm was estimated if only six sections were used, with a reduction in
      radiation of about 65%. CONCLUSION: It is possible to obtain the same
      radiological information from six pre-selected CT cuts as it is from a full
      pulmonary CT scan, thereby markedly reducing radiation exposure for children who
      will require repeat investigations in the future.

PMID- 16449256
TI  - Significant correlations between the flow volume of patent ductus venosus and
      early neonatal liver function: possible involvement of patent ductus venosus in
      postnatal liver function.
AB  - BACKGROUND: The biochemical features of portosystemic venous shunt with high flow
      volume are hypergalactosaemia, hyperammonaemia, prolonged blood coagulation time,
      and raised serum bile acid concentration. The ductus venosus remains open with
      shunt flow in most neonates for a certain period after birth. However, the
      effects of blood flow through the ductus venosus on neonatal liver function
      remain unclear. OBJECTIVE: To elucidate the effect of patency of the ductus
      venosus on liver function in early neonates. METHODS: Subjects were divided into
      three groups by gestational age (group I, 29-32 weeks; group II, 33-36 weeks;
      group III, 37-41 weeks). The shunt flow volume through the ductus venosus was
      examined serially using ultrasonography, and correlations between flow volume and
      liver function in the respective groups were calculated during the first week
      after birth. RESULTS: Group I had a higher flow volume and later functional
      closure than the other two groups. Plasma ammonia and serum total bile acid
      concentrations correlated with flow volume in groups I and II, and blood
      galactose and galactose 1-phosphate concentrations correlated significantly with
      flow volume in group III. Percentage hepaplastin also correlated significantly
      with flow volume in all groups, but plasma vitamin K concentration did not in any
      group. CONCLUSIONS: Patent ductus venosus has a considerable effect on crucial
      liver functions such as ammonia detoxification, blood coagulation, and regulation
      of serum total bile acid concentration in early neonates.

PMID- 16449257
TI  - Moderately premature infants at Kaiser Permanente Medical Care Program in
      California are discharged home earlier than their peers in Massachusetts and the
      United Kingdom.
AB  - OBJECTIVE: To compare gestational age at discharge between infants born at 30
      34(+6) weeks gestational age who were admitted to neonatal intensive care units
      (NICUs) in California, Massachusetts, and the United Kingdom. DESIGN: Prospective
      observational cohort study. SETTING: Fifty four United Kingdom, five California,
      and five Massachusetts NICUs. SUBJECTS: A total of 4359 infants who survived to
      discharge home after admission to an NICU. MAIN OUTCOME MEASURES: Gestational age
      at discharge home. RESULTS: The mean (SD) postmenstrual age at discharge of the
      infants in California, Massachusetts, and the United Kingdom were 35.9 (1.3),
      36.3 (1.3), and 36.3 (1.9) weeks respectively (p = 0.001). Compared with the
      United Kingdom, adjusted discharge of infants occurred 3.9 (95% confidence
      interval (CI) 1.4 to 6.5) days earlier in California, and 0.9 (95% CI -1.2 to
      3.0) days earlier in Massachusetts. CONCLUSIONS: Infants of 30-34(+6) weeks
      gestation at birth admitted and cared for in hospitals in California have a
      shorter length of stay than those in the United Kingdom. Certain characteristics
      of the integrated healthcare approach pursued by the health maintenance
      organisation of the NICUs in California may foster earlier discharge. The
      California system may provide opportunities for identifying practices for
      reducing the length of stay of moderately premature infants.

PMID- 16449258
TI  - A prospective comparison of severity scores for identifying patients with severe
      community acquired pneumonia: reconsidering what is meant by severe pneumonia.
AB  - BACKGROUND: Several severity scores have been proposed to predict patient outcome
      and to guide initial management of patients with community acquired pneumonia
      (CAP). Most have been derived as predictors of mortality. A study was undertaken
      to compare the predictive value of these tools using different clinically
      meaningful outcomes as constructs for "severe pneumonia". METHODS: A prospective
      cohort study was performed of all patients presenting to the emergency department
      with an admission diagnosis of CAP from March 2003 to March 2004. Clinical and
      laboratory features at presentation were used to calculate severity scores using
      the pneumonia severity index (PSI), the revised American Thoracic Society score
      (rATS), and the British Thoracic Society (BTS) severity scores CURB, modified BTS
      severity score, and CURB-65. The sensitivity, specificity, positive and negative
      predictive values were compared for four different outcomes (death, need for ICU
      admission, and combined outcomes of death and/or need for ventilatory or
      inotropic support). RESULTS: 392 patients were included in the analysis; 37
      (9.4%) died and 26 (6.6%) required ventilatory and/or inotropic support. The
      modified BTS severity score performed best for all four outcomes. The PSI
      (classes IV+V) and CURB had a very similar performance as predictive tools for
      each outcome. The rATS identified the need for ICU admission well but not
      mortality. The CURB-65 score predicted mortality well but performed less well
      when requirement for ICU was included in the outcome of interest. When the
      combined outcome was evaluated (excluding patients aged >90 years and those from
      nursing homes), the best predictors were the modified BTS severity score
      (sensitivity 94.3%) and the PSI and CURB score (sensitivity 83.3% for both).
      CONCLUSIONS: Different severity scores have different strengths and weaknesses as
      prediction tools. Validation should be done in the most relevant clinical
      setting, using more appropriate constructs of "severe pneumonia" to ensure that
      these potentially useful tools truly deliver what clinicians expect of them.

PMID- 16449259
TI  - Diagnostic and prognostic value of serum antibodies against Pseudomonas
      aeruginosa in cystic fibrosis.
AB  - BACKGROUND: Eradication of Pseudomonas aeruginosa in patients with cystic
      fibrosis (CF) is possible if initiated early in the course of colonisation. To
      detect P aeruginosa as early as possible is therefore a major goal. This study
      was undertaken to validate a commercialised test for the detection of serum
      Pseudomonas antibodies in patients with CF. METHODS: A representative cross
      sectional analysis of serum antibodies against three Pseudomonas antigens
      (alkaline protease, elastase, and exotoxin A) was performed in 183 patients with
      CF of mean age 16.7 years and FEV1 85.9% predicted. The results were correlated
      with microbiological results from the previous 2 years to calculate sensitivity,
      specificity, positive and negative predictive values. The following 2 years were
      assessed to determine prognostic predictive values. RESULTS: A combination of all
      three tested antibodies yielded the best results with a sensitivity of 86%,
      specificity of 96%, and a positive predictive value of 97%. These values were
      higher if only patients in whom sputum cultures were available were considered (n
      = 76, sensitivity 95%, specificity 100%, positive predictive value 100%). The
      prognostic positive predictive value was high in intermittently infected patients
      (83%) but low in patients free of infection (33%), whereas the prognostic
      negative predictive value was high in patients free of infection (78%) and low in
      intermittently infected patients (58%). CONCLUSIONS: Regular determination of
      serum antibodies may be useful in CF patients with negative or intermittent but
      not with positive P aeruginosa status. A rise in antibody titres indicates
      probable infection and eradication treatment may be initiated even in the absence
      of microbiological detection of P aeruginosa.

PMID- 16449260
TI  - Gender differentials of pulmonary tuberculosis transmission and reactivation in
      an endemic area.
AB  - BACKGROUND: In most low income countries there are twice as many cases of
      tuberculosis (TB) reported among men than among women, a difference commonly
      attributed to biological and epidemiological characteristics as well as
      socioeconomic and cultural barriers in access to health care. The World Health
      Organization has encouraged gender specific comparisons in TB rates to determine
      whether women with TB are less likely than men with TB to be diagnosed, reported,
      and treated. A study was undertaken to identify gender based differences in
      patients with pulmonary TB and to use this information to improve TB control
      efforts. METHODS: Individuals with a cough for more than 2 weeks in southern
      Mexico were screened from March 1995 to April 2003. Clinical and
      mycobacteriological information (isolation, identification, drug susceptibility
      testing and IS6110 based genotyping, and spoligotyping) was collected from those
      with bacteriologically confirmed pulmonary TB. Patients were treated in
      accordance with official norms and followed to ascertain treatment outcome,
      retreatment, and vital status. RESULTS: 623 patients with pulmonary TB were
      enrolled. The male:female incidence rate ratio for overall, reactivated, and
      recently transmitted disease was 1.58 (95% CI 1.34 to 1.86), 1.64 (95% CI 1.36 to
      1.98), and 1.41 (95% CI 1.01 to 1.96), respectively. Men were more likely than
      women to default from treatment (adjusted OR 3.30, 95% CI 1.46 to 7.43), to be
      retreated (hazard ratio (HR) 3.15, 95% CI 1.38 to 7.22), and to die from TB (HR
      2.23, 95% CI 1.25 to 3.99). CONCLUSIONS: Higher rates of transmitted and
      reactivated disease and poorer treatment outcomes among men are indicators of
      gender differentials in the diagnosis and treatment of pulmonary TB, and suggest
      specific strategies in endemic settings.

PMID- 16449261
TI  - Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA
      measurement in sputum of asthma patients.
AB  - BACKGROUND: Asthma is a chronic inflammatory disorder of the airways driven by T
      cell activation. Th2 cells and their cytokines are thought to play a role in the
      pathophysiology of allergic as well as non-allergic asthma. METHODS: Airway cells
      were obtained by sputum induction from 15 healthy and 39 asthmatic individuals
      and the airway T cell cytokine profiles (interleukin (IL)-4, IL-5, IL-13, IL-10
      and interferon (IFN)-gamma) at the mRNA level were studied by real time RT-PCR.
      RESULTS: Asthma patients had increased expression of IL-5 (p = 0.001) and IL-13
      (p = 0.03) mRNA in sputum compared with non-asthmatic controls. IL-4 mRNA and IFN
      gamma mRNA were detectable in the sputum of 44% and 21% of patients,
      respectively, but not in controls. Sputum IL-10 mRNA levels did not differ
      significantly between patients and controls. Sputum mRNA expression levels of IL
      4, IL-5, and IL-13 were significantly correlated with the percentage of
      eosinophils and were higher in subjects with allergic asthma than in those with
      non-allergic asthma (p = 0.03, p = 0.02 and p = 0.0002, respectively); they did
      not differ between mild asthmatic subjects and those with moderate to severe
      asthma. In contrast, IFN-gamma mRNA expression was higher in non-allergic than in
      allergic patients (p = 0.04) and higher in patients with moderate to severe
      asthma than in those with mild asthma (p<0.01). Sputum IL-5 mRNA levels (but not
      the other cytokine mRNA levels) were also correlated with exhaled nitric oxide
      (eNO) and with bronchial hyperreactivity expressed as the histamine concentration
      resulting in a 20% decrease in forced expiratory volume in 1 second. CONCLUSION:
      Real time RT-PCR analysis of mRNA in induced sputum confirms a predominance of
      Th2 cytokines in both allergic and non-allergic asthma. IL-5 levels reflect
      eosinophil infiltration as well as eNO levels and hyperreactivity, and levels of
      the Th1 cytokine IFN-gamma indicate asthma severity. The technique is a promising
      tool for use in further studies of asthma severity and disease activity.

PMID- 16449262
TI  - Surgery for non-small cell lung cancer: systematic review and meta-analysis of
      randomised controlled trials.
AB  - BACKGROUND: Surgery is considered the treatment of choice for patients with
      resectable stage I and II (and some patients with stage IIIA) non-small cell lung
      cancer (NSCLC), but there have been no previously published systematic reviews.
      METHODS: A systematic review and meta-analysis of randomised controlled trials
      was conducted to determine whether surgical resection improves disease specific
      mortality in patients with stages I-IIIA NSCLC compared with non-surgical
      treatment, and to compare the efficacy of different surgical approaches. RESULTS:
      Eleven trials were included. No studies had untreated control groups. In a pooled
      analysis of three trials, 4 year survival was superior in patients undergoing
      resection with stage I-IIIA NSCLC who had complete mediastinal lymph node
      dissection compared with lymph node sampling (hazard ratio estimated at 0.78 (95%
      CI 0.65 to 0.93)). Another trial reported an increased rate of local recurrence
      in patients with stage I NSCLC treated with limited resection compared with
      lobectomy. One small study reported a survival advantage among patients with
      stage IIIA NSCLC treated with chemotherapy followed by surgery compared with
      chemotherapy followed by radiotherapy. No other trials reported significant
      improvements in survival after surgery compared with non-surgical treatment.
      CONCLUSION: It is difficult to draw conclusions about the efficacy of surgery for
      locoregional NSCLC because of the small number of participants studied and
      methodological weaknesses of the trials. However, current evidence suggests that
      complete mediastinal lymph node dissection is associated with improved survival
      compared with node sampling in patients with stage I-IIIA NSCLC undergoing
      resection.

PMID- 16449263
TI  - Previous tumour as a prognostic factor in stage I non-small cell lung cancer.
AB  - OBJECTIVE: To evaluate the effect of comorbidity as an independent prognostic
      factor in lung cancer. METHOD: Data on 2991 consecutive cases of lung cancer were
      collected prospectively from 19 Spanish hospitals between 1993 and 1997 by the
      Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and
      Thoracic Surgery (GCCB-S). To evaluate the effect of comorbidity on survival,
      1121 patients with non-small cell lung cancer (NSCLC) in pathological stage I who
      underwent complete resection were selected, excluding operative mortality. The
      presence of specific comorbidities at the time of thoracotomy was registered
      prospectively. RESULTS: Cox regression analysis showed that tumour size (0-2, 2
      4, 4-7, >7 cm) (HR 1.45 95% CI 1.08 to 1.95), 1.86 (95% CI 1.38 to 2.51), 2.84
      (95% CI 1.98 to 4.08)), the presence of a previous tumour (HR 1.45 (95% CI 1.17
      to 1.79)) and age (HR 1.02 (95% CI 1.01 to 1.03)) had a significant prognostic
      association with survival. This study excluded the presence of visceral pleural
      involvement or other comorbidities as independent variables. CONCLUSION: The
      presence of a previous tumour is an independent prognostic factor in pathological
      stage I NSCLC with complete resection, increasing the probability of death by 1.5
      times at 5 years. It is independent of other comorbidities, TNM classification
      and age.

PMID- 16449264
TI  - Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial
      inflammation in asthma.
AB  - BACKGROUND: Addition of the long acting beta2 agonist salmeterol to inhaled
      corticosteroids leads to better symptomatic asthma control than increasing the
      dose of inhaled corticosteroids. However, little is known about the long term
      effects of adding salmeterol on the asthmatic inflammatory process, control of
      which is considered important for the long term outcome of asthma. METHODS: After
      a 4 week fluticasone run-in period, 54 patients with allergic asthma were
      randomised to receive twice daily treatment with fluticasone 250 microg with or
      without salmeterol 50 microg for 1 year in a double blind, parallel group design
      (total daily dose of fluticasone 500 microg in both treatment groups). Primary
      outcomes were sputum eosinophil numbers and eosinophil cationic protein
      concentrations. Secondary outcomes were neutrophil associated sputum parameters
      and a respiratory membrane permeability marker. The effects on allergen induced
      changes were determined before and at the end of the treatment period. RESULTS:
      Adding salmeterol to fluticasone resulted in improved peak expiratory flow,
      symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p <
      0.05 for all). There was no sustained effect on sputum cell differential counts
      and cytokine concentrations during the treatment period or on changes induced by
      allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol
      significantly reduced sputum ratios of alpha2-macroglobulin and albumin during
      the treatment period (p = 0.001). CONCLUSIONS: The addition of salmeterol to
      fluticasone produces no sustained effect on allergen induced cellular bronchial
      inflammation but leads to a significant improvement in size selectivity of plasma
      protein permeation across the respiratory membrane. This may contribute to the
      improved clinical outcome seen in patients with allergic asthma when a long
      acting beta2 agonist is combined with inhaled corticosteroids.

PMID- 16449265
TI  - Hyperglycaemia is associated with poor outcomes in patients admitted to hospital
      with acute exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Hyperglycaemia is associated with poor outcomes from pneumonia,
      myocardial infarction and stroke, but the effect of blood glucose on outcomes
      from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has
      not been established. Recent UK guidelines do not comment on measurement or
      control of blood glucose in AECOPD. A study was therefore undertaken to determine
      the relationship between blood glucose concentrations, length of stay in
      hospital, and mortality in patients admitted with AECOPD. METHODS: Data were
      retrieved from electronic records for patients admitted with AECOPD with lower
      respiratory tract infection in 2001-2. The patients were grouped according to
      blood glucose quartile (group 1, <6 mmol/l (n = 69); group 2, 6.0-6.9 mmol/l (n =
      69); group 3, 7.0-8.9 mmol/l (n = 75); and group 4, >9.0 mmol/l (n = 71)).
      RESULTS: The relative risk (RR) of death or long inpatient stay was significantly
      increased in group 3 (RR 1.46, 95% CI 1.05 to 2.02, p = 0.02) and group 4 (RR
      1.97, 95% CI 1.33 to 2.92, p < 0.0001) compared with group 1. For each 1 mmol/l
      increase in blood glucose the absolute risk of adverse outcomes increased by 15%
      (95% CI 4 to 27), p = 0.006. The risk of adverse outcomes increased with
      increasing hyperglycaemia independent of age, sex, a previous diagnosis of
      diabetes, and COPD severity. Isolation of multiple pathogens and Staphylococcus
      aureus from sputum also increased with increasing blood glucose. CONCLUSION:
      Increasing blood glucose concentrations are associated with adverse clinical
      outcomes in patients with AECOPD. Tight control of blood glucose reduces
      mortality in patients in intensive care or following myocardial infarction. A
      prospective study is now required to determine whether control of blood glucose
      can also improve outcomes from AECOPD.

PMID- 16449266
TI  - Objective measurement of cough during pulmonary exacerbations in adults with
      cystic fibrosis.
AB  - BACKGROUND: Little is known about cough frequency in adults with cystic fibrosis
      (CF). This study aimed to determine (1) daytime and overnight cough rates in
      patients with CF at the beginning and end of a course of antibiotics for
      treatment of an exacerbation; (2) the relationship between cough frequencies and
      standard clinical measures of disease; and (3) the relationship between objective
      cough rates and the subjective assessment of cough. METHODS: Nineteen adult
      patients admitted with a pulmonary exacerbation performed daytime and overnight
      sound recordings on admission; 13 had repeat recordings prior to discharge.
      Coughs were manually quantified in cough seconds (time spent coughing). Patients
      subjectively scored their cough using a visual analogue scale (VAS) and numerical
      score. Lung function, C-reactive protein (CRP) levels, and sputum weights were
      recorded. RESULTS: Cough rates fell substantially with treatment; median fall in
      cough rate was 51.3% (IQR 32.3-77.5) (p<0.001) for daytime and 72.2% (28.6-90.1)
      (p = 0.049) for overnight. Multivariate regression analyses showed that forced
      expiratory volume in 1 second and CRP levels predicted overnight cough rates on
      admission. On discharge, sputum volume predicted daytime cough rates. Only the
      change in overnight VAS correlated with the change in objective cough rates.
      CONCLUSIONS: The cough rate significantly decreases with treatment of a pulmonary
      exacerbation in adults with CF. Lung function, sputum volume, and CRP influences
      the cough rate, with the effects differing from day to night and between
      admission and discharge. Subjective reporting of a nocturnal cough may indicate a
      pulmonary exacerbation of CF in adults.

PMID- 16449267
TI  - Enhanced upregulation of smooth muscle related transcripts by TGF beta2 in
      asthmatic (myo) fibroblasts.
AB  - BACKGROUND: Transforming growth factor beta (TGF beta) upregulates a number of
      smooth muscle specific genes in (myo)fibroblasts. As asthma is characterised by
      an increase in airway smooth muscle, we postulated that TGFbeta(2) favours
      differentiation of asthmatic (myo)fibroblasts towards a smooth muscle phenotype.
      METHODS: Primary fibroblasts were grown from bronchial biopsy specimens from
      normal (n = 6) and asthmatic (n = 7) donors and treated with TGF beta2 to induce
      myofibroblast differentiation. The most stable genes for normalisation were
      identified using RT-qPCR and the geNorm software applied to a panel of 12
      "housekeeping" genes. Expression of alpha-smooth muscle actin (alpha SMA), heavy
      chain myosin (HCM), calponin 1 (CPN 1), desmin, and gamma-actin were measured by
      RT-qPCR. Protein expression was assessed by immunocytochemistry and western
      blotting. RESULTS: Phospholipase A2 and ubiquitin C were identified as the most
      stably expressed and practically useful genes for normalisation of gene
      expression during myofibroblast differentiation. TGF beta2 induced mRNA
      expression for all five smooth muscle related transcripts; alpha SMA, HCM and CPN
      1 protein were also increased but desmin protein was not detectable. Although
      there was no difference in basal expression, HCM, CPN 1 and desmin were induced
      to a significantly greater extent in asthmatic fibroblasts than in those from
      normal controls (p = 0.041 and 0.011, respectively). CONCLUSIONS: Although TGF
      beta2 induced the transcription of several smooth muscle related genes, not all
      were translated into protein. Thus, while TGF beta2 is unable to induce a bona
      fide smooth muscle cell phenotype, it may "prime" (myo)fibroblasts for further
      differentiation, especially if the cells are derived from asthmatic airways.

PMID- 16449269
TI  - Pre-flight testing of preterm infants with neonatal lung disease: a retrospective
      review.
AB  - BACKGROUND: The low oxygen environment during air travel may result in hypoxia in
      patients with respiratory disease. However, little information exists on the
      oxygen requirements of infants with respiratory disease planning to fly. A study
      was undertaken to identify the clinical factors predictive of an in-flight oxygen
      requirement from a retrospective review of hypoxia challenge tests (inhalation of
      14-15% oxygen for 20 minutes) in infants referred for fitness to fly assessment.
      METHODS: Data from 47 infants (median corrected age 1.4 months) with a history of
      neonatal lung disease but not receiving supplemental oxygen at the time of
      hypoxia testing are reported. The neonatal and current clinical information of
      the infants were analysed in terms of their ability to predict the hypoxia test
      results. RESULTS: Thirty eight infants (81%) desaturated below 85% and warranted
      prescription of supplemental in-flight oxygen. Baseline oxygen saturation was
      >95% in all infants. Age at the time of the hypoxia test, either postmenstrual or
      corrected, significantly predicted the outcome of the hypoxia test (odds ratio
      0.82; 95% confidence intervals 0.62 to 0.95; p = 0.005). Children passing the
      hypoxia test were significantly older than those requiring in-flight oxygen
      (median corrected age (10-90th centiles) 12.7 (3.0-43.4) v 0 (-0.9-10.9) months;
      p < 0.0001). CONCLUSIONS: A high proportion of ex-preterm infants not currently
      requiring supplemental oxygen referred for fitness-to-fly assessment and less
      than 12 months corrected age are at a high risk of requiring in-flight oxygen.
      Referral of this patient group for fitness to fly assessment including a hypoxia
      test may be indicated.

PMID- 16449268
TI  - UK National COPD Audit 2003: Impact of hospital resources and organisation of
      care on patient outcome following admission for acute COPD exacerbation.
AB  - BACKGROUND: Acute chronic obstructive pulmonary disease (COPD) exacerbations use
      many hospital bed days and have a high rate of mortality. Previous audits have
      shown wide variability in the length of stay and mortality between units not
      explained by patient factors. This study aimed to explore associations between
      resources and organisation of care and patient outcomes. METHODS: 234 UK acute
      hospitals each prospectively identified 40 consecutive acute COPD admissions,
      documenting process of care and outcomes from a retrospective case note audit.
      Units also completed a resources and organisation of care proforma. RESULTS: Data
      for 7529 patients were received. Inpatient mortality was 7.4% and mortality at 90
      days was 15.3%; the readmission rate was 31.4%. Mean length of stay for
      discharged patients was 8.7 days (median 6 days). Wide variation was observed in
      all outcomes between hospitals. Both inpatient mortality (odds ratio (OR) 0.67,
      CI 0.50 to 0.90) and 90 day mortality (OR 0.75, CI 0.60 to 0.94) were associated
      with a staff ratio of four or more respiratory consultants per 1000 hospital
      beds. The length of stay was reduced in units with more respiratory consultants,
      better organisation of care scores, an early discharge scheme, and local COPD
      management guidelines. CONCLUSIONS: Units with more respiratory consultants and
      better quality organised care have lower mortality and reduced length of hospital
      stay. This may reflect unit resource richness. Dissemination of good
      organisational practice and recruitment of more respiratory specialists offers
      the potential for improved outcomes for hospitalised COPD patients.

PMID- 16449270
TI  - How long should outpatient pulmonary rehabilitation be? A randomised controlled
      trial of 4 weeks versus 7 weeks.
AB  - BACKGROUND: The evidence of benefit for pulmonary rehabilitation (PR) programmes
      is established. However, the optimal duration of a PR programme is not known. A
      randomised controlled trial was undertaken in patients with chronic obstructive
      pulmonary disease (COPD) to assess whether a 4 week PR programme was equivalent
      to our conventional 7 week PR programme at equivalent time points of 7 weeks and
      6 months. METHODS: One hundred patients (56 men) with stable COPD of mean (SD)
      age 70 (8) years and forced expiratory volume in 1 second (FEV1) 1.13 (0.50)
      litres were randomised to either a 7 week (n = 50) or 4 week (n = 50) supervised
      PR programme. Patients were assessed at baseline, at completion of the supervised
      PR programme, and 6 months later. Patients randomised to the 4 week group were
      also assessed at the 7 week time point. Outcome measures were the Incremental
      Shuttle Walk Test, Endurance Shuttle Walk Test (ESWT), Chronic Respiratory
      Questionnaire-Self Reported, and the Breathing Problems Questionnaire. RESULTS:
      Forty one patients in each group completed the PR programme. Patients made
      significant within group improvements after supervised rehabilitation. There were
      no statistically significant differences between the groups for any other measure
      at the 7 week or 6 month time points, except that patients in the 4 week group
      attained higher ESWT times (mean difference 124 seconds (95% CI 17.00 to 232.16),
      p = 0.024) at the 7 week time point. CONCLUSIONS: A shortened 4 week supervised
      PR programme is equivalent to a 7 week supervised PR programme at the comparable
      time points of 7 weeks and 6 months.

PMID- 16449271
TI  - Longer term follow up of aerobic capacity in children affected by severe acute
      respiratory syndrome (SARS).
AB  - BACKGROUND: A study was undertaken to investigate the aerobic capacity and
      pulmonary function of children 6 and 15 months after the diagnosis of severe
      acute respiratory syndrome (SARS). METHODS: Thirty four patients of mean age 14.7
      years completed both pulmonary function and maximal aerobic capacity tests at 6
      months. All had normal clinical examination and were asymptomatic. Their exercise
      responses were compared with a group of healthy controls. Complete data were
      collected on 27 of the original 34 cases at 15 months. RESULTS: Compared with
      normal controls, the patient group had significantly lower absolute and mass
      related peak oxygen consumption (peak V o(2) (p<0.01)), higher ventilatory
      equivalent for oxygen (p<0.01), lower oxygen pulse (p<0.01), and a lower oxygen
      uptake efficiency slope (p<0.01) at 6 months. This impairment was unexpected and
      out of proportion with the degree of lung function abnormality. Residual high
      resolution computed tomography of thorax (HRCT) abnormalities were present in 14
      patients. Those with abnormal HRCT findings had significantly lower mass related
      peak V o(2) than subjects with normal radiology (p<0.01). Absolute and mass
      related peak V o(2) in the patient group remained impaired at 15 months despite
      normalisation of lung function in all patients. CONCLUSIONS: The mechanism for
      the reduced aerobic capacity in children following SARS is not fully understood,
      but it is probably a consequence of impaired perfusion to the lungs at peak
      exercise and deconditioning.

PMID- 16449272
TI  - Effect of training on patient outcomes following lobectomy.
AB  - BACKGROUND: Little is known about the effect of surgical training on outcomes in
      thoracic surgery. The impact of surgeon training on outcomes following lung
      resection was examined, focusing on lobectomy as a marker operation. METHODS: 328
      consecutive patients who underwent lobectomy at our institution between 1 October
      2001 and 30 June 2003 were studied. Data were collected prospectively during the
      patient's admission as part of routine clinical practice and validated by a
      designated audit officer. Patient characteristics and postoperative outcomes were
      compared between trainee led and consultant led operations. RESULTS: In 115 cases
      (35.1%) the operation was performed by a trainee thoracic surgeon as the first
      operator. There were no significant differences in patient characteristics
      between the two groups. In-hospital mortality was similar for operations led by
      trainees and consultants (3.5% and 2.8%, respectively; p > 0.99). Outcomes in the
      two groups did not differ significantly with respect to respiratory,
      cardiovascular, renal, neurological, chest infection, bleeding, and
      gastrointestinal complications. Survival rates at 1 year were 82.6% for
      procedures led by trainees compared with 81.7% for procedures led by consultants
      (p = 0.83). CONCLUSIONS: With appropriate supervision, trainee thoracic surgeons
      can perform lobectomies safely without compromising short or intermediate term
      patient outcome.

PMID- 16449273
TI  - Antibiotic treatment and factors influencing short and long term outcomes of
      acute exacerbations of chronic bronchitis.
AB  - BACKGROUND: The MOSAIC study compared moxifloxacin with three standard antibiotic
      regimens in patients with Anthonisen type 1 acute exacerbations of chronic
      bronchitis (AECB). Further exploratory analyses were performed to identify
      prognostic factors of short and long term clinical outcomes and their value for
      clinical research. METHODS: Outpatients aged > or =45 years were screened between
      AECB episodes, randomised to treatment upon presenting with an AECB, assessed 7
      10 days after study treatment, and followed monthly until a new AECB or for up to
      9 months. Logistic regression assessed the predictive factors for clinical cure
      (return to pre-AECB status) and clinical success (cure or improvement), and a
      stepwise Cox regression model time to a composite event (failure of study
      treatment, new AECB, or further antibiotic treatment for AECB). RESULTS: In
      multivariate analyses, clinical cure was positively influenced by treatment with
      moxifloxacin (odds ratio (OR) 1.49; 95% CI 1.08 to 2.04) while cardiopulmonary
      disease (OR 0.59; 95% CI 0.38 to 0.90), forced expiratory volume in 1 second
      (FEV1) <50% predicted (OR 0.48; 95% CI 0.35 to 0.67), and > or =4 AECBs in the
      previous year (OR 0.68; 95% CI 0.48 to 0.97) predicted a poorer outcome. For
      clinical success, treatment with moxifloxacin had a positive influence (OR 1.57;
      95% CI 1.03 to 2.41) while cardiopulmonary disease (OR 0.41; 95% CI 0.25 to 0.68)
      and use of acute bronchodilators (OR 0.50; 95% CI 0.30 to 0.84) predicted a
      poorer outcome. The occurrence of the composite event was influenced by
      antibiotic treatment (hazard ratio (HR) 0.82; 95% CI 0.68 to 0.98), age > or =65
      years (HR 1.22; 95% CI 1.01 to 1.47), FEV1<50% predicted (HR 1.27; 95% CI 1.05 to
      1.53), > or =4 AECBs in previous year (HR 1.63; 95% CI 1.34 to 1.99), and acute
      bronchodilator use (HR 1.48; 95% CI 1.17 to 1.87). For the composite event the
      beneficial effect of moxifloxacin was primarily seen in patients aged > or =65
      years. CONCLUSION: Despite selection of a homogeneous population of patients with
      chronic bronchitis, between group differences relating to antibiotic treatment
      could still be confounded by factors related to medical history, severity of
      disease, and use of concomitant medications. The design of future clinical trials
      should take these factors into account.

PMID- 16449274
TI  - Childhood asthma in South London: trends in prevalence and use of medical
      services 1991-2002.
AB  - BACKGROUND: Hospital admission rates for asthma in Britain rose during the 1980s
      and fell during the 1990s, but less is known about recent trends in the
      prevalence of asthma. METHODS: In 1991 and 2002 the same questionnaire was
      distributed to parents of all school pupils in year 3 (aged 7-8 years) in the
      London borough of Croydon. Parents of currently wheezy children were then invited
      for home interview (100% targeted in 1991, 66% in 2002). RESULTS: The prevalence
      of wheeze during the previous year increased from 12.9% in 1991 to 17.8% in 2002
      (prevalence ratio 1.39 (95% CI 1.23 to 1.56)). Increases were observed in
      frequent (1.54 (95% CI 1.16 to 2.03)) and infrequent attacks, severe speech
      limiting episodes (2.25 (95% CI 1.34 to 3.77)), and night waking (1.36 (95% CI
      1.07 to 1.72)), and in the reported use of steroids (19.9% v 64.1% of currently
      wheezy children). Nevertheless, the proportions reporting a visit to the GP at
      his/her surgery for wheeze in the previous year (prevalence ratio 1.15 (95% CI
      0.91 to 1.45)) or an outpatient visit (0.98 (95% CI 0.49 to 1.94)) changed little
      and an increase in reported casualty attendance (1.66 (95% CI 0.89 to 3.07)) was
      non-significant. CONCLUSIONS: There is evidence of an increase in the prevalence
      of asthma among British primary school children between 1991 and 2002. The
      absence of a corresponding increase in health service utilisation data may
      reflect more widespread prophylactic treatment and/or changes in the use and
      provision of medical services.

PMID- 16449275
TI  - Comprehensive immunohistological analysis of the endothelin system in human
      kidney grafts.
AB  - BACKGROUND: In experimental models of renal transplantation, upregulation of the
      endothelin (ET) system and amelioration of renal injury by ET-receptor blockers
      have been documented. In contrast, little information is available on the
      expression of the ET system in human kidney allografts. It was the purpose of the
      present study to analyse by immunohistology the expression of ET-1 as well as of
      the two ET receptors (ET-RA and ET-RB) in the different cells and compartments of
      kidney grafts and control kidneys. METHODS: Fifty-five graft biopsies were taken
      from 55 kidney allograft recipients (mean age: 32+/-2.8 years) who were all on a
      calcineurin inhibitor. The indication for biopsies was delayed graft function or
      suspected rejection. The underlying diagnoses were acute allograft rejection (n =
      14), chronic allograft nephropathy (n = 14), cyclosporin A (CSA) toxicity (n =
      10), post-operative acute tubular necrosis (ATN) (n = 11) and recurrent primary
      disease (n = 6). As control, tissues of non-grafted kidneys with ATN (mean age:
      35+/-24 years), of primary glomerulonephritis (mean age: 69+/-10 years) and of
      non-tumour-bearing parts of eight tumour nephrectomy specimens (mean age: 67+/-5
      years) were assessed. The biopsies were scored using the 1997 Banff criteria.
      Expression of ET-1, ET-RA and ET-RB as well as of vascular endothelial growth
      factor was evaluated by immunohistochemistry and a semi-quantitative scoring
      system. Interstitial infiltrating cells were characterized using antibodies
      against T cells, B cells and macrophages (CD3, CD20 and CD68). RESULTS: Control
      cases showed only faint expression of ET-1 in glomeruli (in podocytes and
      endothelial cells), whereas marked expression was seen in distal, but less in
      proximal tubular cells. The interstitium was completely negative. ET-1 expression
      was seen in vascular endothelial cells (VEC) and vascular smooth muscle cells
      (VSMC). Only faint expression of ET-RA and ET-RB was found in glomeruli and
      tubuli (distal more than proximal). Marked ET-RA and ET-RB expression was seen in
      VEC and VSMC. In all transplanted kidneys, irrespective of the underlying
      diagnosis, expression of ET-1, ET-RA and ET-RB was markedly higher compared with
      control kidneys. ET-1 was strikingly upregulated in glomeruli and tubuli, but
      surprisingly not in the vasculature of grafts with CSA toxicity. Expression of ET
      RB was markedly increased in CSA toxicity in glomeruli, tubuli and vessels. In
      grafts with ATN and acute rejection, pronounced expression of ET-RA was noted.
      There was a strong correlation between proteinuria and expression of ET-1 in
      glomeruli and proximal tubuli and of ET-RB in proximal tubuli. CONCLUSIONS: The
      above data in human kidney allograft biopsies are consistent with an important
      role of the ET system in different types of renal allograft damage. This finding
      extends and clarifies the somewhat contradictory results in animal models.

PMID- 16449276
TI  - Urine IgM excretion predicts outcome in ANCA-associated renal vasculitis.
AB  - BACKGROUND: Renal function at diagnosis is a strong predictor not only of renal
      survival but also of patient survival of those with anti-neutrophil cytoplasmic
      antibody (ANCA)-associated small vessel vasculitis (ASVV). Apart from the renal
      function at diagnosis, there are no other established risk factors for renal
      outcome in ASVV. We have previously reported that in other forms of glomerular
      diseases, an increased urine excretion of IgM is an early marker of poor renal
      outcome. METHODS: In this single-centre observational study, the prognostic
      significance of urine IgM excretion and other selected prognostic markers was
      studied in 83 consecutive patients (49 males, 34 females) with ASVV with renal
      involvement. RESULTS: Patient survival at 1 and 5 years was 93 and 77%,
      respectively, and the corresponding figures for renal survival censored for death
      were 84 and 76%. Univariate analysis indicated that patient survival was
      inversely associated with age, male sex, serum creatinine, low serum albumin and
      high urine IgM excretion. Renal survival was inversely associated with serum
      creatinine, albuminuria and urine IgM. Multivariate analysis determined that only
      old age and high urine IgM excretion were independent predictors of patient
      survival [odds ratio (OR) = 11.2 and 4.4, respectively, P<0.01]. Urine excretion
      of IgM was the only independent predictor of end-stage renal disease (OR = 19.8,
      P = 0.004). Overall, 35% of the patients reached the composite end-point of
      either death or renal replacement therapy. Urine IgM excretion was the most
      potent single predictor of such an outcome (OR = 7.7, P = 0.000). CONCLUSION: The
      occurrence of an increased amount of IgM in urine at presentation is a strong
      marker of poor prognosis for patients with ANCA-associated renal vasculitis.

PMID- 16449277
TI  - Impact of renin angiotensin system blockade on night to day blood pressure ratio
      in diabetic nephropathy.

PMID- 16449278
TI  - Combined renal replacement therapy for severe metformin-induced lactic acidosis.

PMID- 16449279
TI  - Tests for latent tuberculosis.

PMID- 16449280
TI  - Successful living-related kidney transplantation in hereditary renal
      hypouricaemia.

PMID- 16449281
TI  - The effect of immunosuppressive therapy on the messenger RNA expression of target
      genes in the urinary sediment of patients with active lupus nephritis.
AB  - BACKGROUND: Previous studies have shown that messenger RNA (mRNA) expression of
      target genes is increased in the urinary sediment of patients with active lupus.
      We study the effect of immunosuppressive therapy on the urinary gene expression
      profile in patients with active lupus nephritis. Method. We recruited nine
      patients with active systemic lupus erythematosus (SLE) and renal disease, and
      required corticosteroid, with or without cytotoxic treatment. They were followed
      for 6 months, urine samples were collected at 0, 4, 12 and 24 weeks and gene
      expression profile was determined by polymerase chain reactions. The pattern of
      gene expression was compared to clinical parameters of therapeutic response.
      RESULTS: Amongst the target genes studied, there was a progressive decline in the
      urinary expression of T-bet, interleukin (IL)-10, transforming growth factor-beta
      (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma (IFN
      gamma) after immunosuppressive treatment, although the change of IFN-gamma was
      not statistically significant. The time course of their urinary expression was
      parallel to the systemic activity as reflected by the systemic lupus
      erythematosus disease activity index (SLEDAI). Throughout the study period, the
      SLEDAI score correlated significantly with the expressions of IFN-gamma (r =
      0.43, P = 0.009), T-bet (r = 0.40, P = 0.016), TGF-beta (r = 0.51, P = 0.002) and
      MCP-1 (r = 0.38, P = 0.022). The anti-double strand(anti-ds)DNA antibody titer
      correlated significantly with the expressions of IFN-gamma (r = 0.45, P = 0.009),
      T-bet (r = 0.37, P = 0.034), IL-10 (r = 0.59, P<0.001), TGF-beta (r = 0.44, P =
      0.010) and MCP-1 (r = 0.49, P = 0.004). On the other hand, the expression level
      of IL-2, IL-4, IL-12, IL-18 and GATA-3 remained static throughout the study
      period. CONCLUSIONS: The mRNA expression of T-bet, IL-10, TGF-beta, MCP-1, and
      probably IFN-gamma in the urinary sediment of patients with active lupus
      nephritis improves with successful immunosuppressive therapy, and the change in
      gene expression profile is in phase with the clinical disease activity.
      Measurement of urinary mRNA expression of target genes may be a potential non
      invasive tool for the monitoring of lupus disease activity.

PMID- 16449282
TI  - Green dialysate: asymptomatic perforated cholecystitis without peritonitis.

PMID- 16449283
TI  - Anaemia and mortality in haemodialysis patients: interaction of propensity score
      for predicted anaemia and actual haemoglobin levels.
AB  - BACKGROUND: Haemoglobin levels in haemodialysis patients could represent unknown
      comorbidities, more severe levels of known comorbidities, as well as therapeutic
      choice. Thus, integrating factors predictive of anaemia with actual haemoglobin
      levels might improve prognostic discrimination. METHODS: We retrospectively
      studied 93,087 patients who started haemodialysis between 1998 and 2000. Clinical
      and treatment factors from months 4 through 9, derived from Medicare claims, were
      used to develop propensity scores for anaemia (mean haemoglobin <11 g/dl).
      Tertiles of propensity scores were interacted with five levels of actual mean
      haemoglobin to form 15 groups, ranging from low (anaemia) probability with (mean)
      haemoglobin <10 g/dl to high probability with haemoglobin >or=13 g/dl. Cox
      proportional hazards regression evaluated mortality and first hospitalization
      among these groups. RESULTS: The anaemia propensity score improved overall
      prognostic discrimination. Propensity score adjustment significantly improved
      prediction of mortality (P<0.0001) after covariate adjustments including
      haemoglobin. For mortality, the highest and lowest adjusted hazard ratios (AHR)
      appeared in these groups, respectively: high probability with haemoglobin <10
      g/dl (AHR 1.64 [1.54, 1.75], P<0.0001), and low probability with haemoglobin 12
      to <13 g/dl (AHR 0.79 [0.74, 0.85], P<0.0001). Higher haemoglobin levels were
      associated with lower mortality even after propensity score adjustment. Similar
      patterns resulted for first hospitalization; however, the interaction was
      significant only for hospitalization (P = 0. 0212). CONCLUSIONS: Integrating
      factors predictive of anaemia improves overall prognostic discrimination.
      Propensity score adjustment refines the prognostic association of haemoglobin
      levels in haemodialysis patients.

PMID- 16449284
TI  - The effect of single and repeatedly high concentrations of C-reactive protein on
      cardiovascular and non-cardiovascular mortality in patients starting with
      dialysis.
AB  - BACKGROUND: Single measurements of C-reactive protein (CRP) predict
      cardiovascular mortality in dialysis patients. However, CRP can be temporarily
      elevated due to infections. Therefore, we investigated the effect of single and
      repeatedly high concentrations of CRP on cardiovascular and non-cardiovascular
      mortality in incident dialysis patients. METHODS: In the Netherlands Cooperative
      Study on the Adequacy of Dialysis (NECOSAD), patients starting with dialysis were
      enrolled between 1997 and 2002. From 635 patients, plasma CRP concentrations were
      determined at 3 and 6 months of follow-up. Concentrations >10 mg/l were regarded
      as 'high'. Patients were followed until time of death, or censored at the end of
      follow-up (1 May 2004). Cox regression models were performed to compare mortality
      between patients with repeatedly low CRP, with varying CRP and with repeatedly
      high CRP. RESULTS: At the end of follow-up, 247 patients had died, of which 107
      patients died of cardiovascular disease (47.8%). Patients with low CRP(3 months)
      and high CRP(6 months) were at increased cardiovascular [adjusted hazard ratio
      (HR): 2.59, 95% CI: 1.25-5.37] and non-cardiovascular (adjusted HR: 2.18, 95% CI:
      1.11-4.28) mortality risk compared with patients with low CRP on both occasions.
      Moreover, patients with high CRP on both occasions had a higher cardiovascular
      (adjusted HR: 1.51, 95% CI: 0.72-3.18) and non-cardiovascular (adjusted HR: 2.25,
      95% CI: 0.96-5.28) mortality risk than patients with high CRP(3 months) and low
      CRP(6 months). CONCLUSIONS: Single and repeatedly high concentrations of CRP (>10
      mg/l) are related to both cardiovascular and non-cardiovascular mortality in
      dialysis patients. A high CRP concentration, therefore, has implications for the
      treatment of cardiovascular as well as non-cardiovascular disease.

PMID- 16449285
TI  - Therapeutic approach in patients with dysnatraemias.
AB  - BACKGROUND: Rapid correction of dysnatraemias is frequently associated with
      increased morbidity and mortality. Therefore, it is important to estimate the
      proper volume and type of infusate required to change the serum sodium
      concentration predictably. The aim of this study is to evaluate the utility
      or/and the accuracy of the Adrogue-Madias formula in managing patients with
      hyponatraemia and hypernatraemia. METHODS: Among the 317 patients who either on
      admission to our internal medicine clinic or during their hospitalization were
      found to have hyponatraemia or hypernatraemia, we studied 189 patients (59.6%) in
      whom the administration of intravenous solutions was required for the correction
      of dysnatraemias. RESULTS: Twelve hours after starting the administration of
      intravenous solutions the anticipated as well as the achieved serum sodium
      concentration were as follows: in volume depleted patients 130.2+/-4.1 vs 131.3+/
      5.2 meq/l (n = 45; P = NS), in syndrome of inappropriate antidiuretic hormone
      secretion (SIADH) patients 127.4+/-5.7 vs 128.9+/-5.9 meq/l (n = 10; P = NS), in
      patients with diuretic-induced hyponatraemia 123.8+/-6 vs 125.5+/-5.6 meq/l (n =
      29; P = NS), in patients with primary polydipsia 122.5+/-0.7 vs 129+/-1.4 meq/l
      (n = 2; P = 0.02), while in patients with hypernatraemia 153.6+/-7.5 vs 156.5+/
      8.9 meq/l (n = 92; P = 0.021). Furthermore, 24 h from the initiation of the
      therapeutic intervention the expected and the achieved serum sodium
      concentrations were 130+/-4 vs 135.6+/-3.3 meq/l (n = 15; P = 0.002) in patients
      with volume depletion, 128.1+/-4.8 vs 130+/-4.5 meq/l (n = 15; P = NS) in
      patients with diuretic-induced hyponatraemia and 151.5+/-6.4 vs 153.3+/-8.3 meq/l
      (n = 67; P = NS) in patients with hypernatraemia. CONCLUSIONS: The formula that
      has been proposed by Adrogue and Madias predicted with relative accuracy the
      changes in serum sodium concentration in almost all patients. Thus, it should be
      considered as a very useful tool for the management of dysnatraemias. However,
      special attention should be paid when this equation is used in patients with
      hyponatraemia due to extracellular volume depletion after euvolaemia's
      restoration and primary polydipsia in order to avoid rapid correction of
      hyponatraemia.

PMID- 16449286
TI  - Role of TGF-beta/GLUT1 axis in susceptibility vs resistance to diabetic
      glomerulopathy in the Milan rat model.
AB  - BACKGROUND: GLUT1 upregulation and increased glucose transport activity may
      contribute to extracellullar matrix (ECM) accumulation characterizing diabetic
      nephropathy (DN). Rats of the Milan hypertensive strain (MHS) are resistant to
      both hypertensive and diabetic renal disease, due to a haemodynamic protection.
      On the contrary, those of the Milan normotensive strain (MNS) develop spontaneous
      glomerulosclerosis, and when rendered diabetic, show typical morphological and
      haemodynamic changes. METHODS: To assess whether susceptibility to diabetic
      glomerulopathy in MNS rats is associated with higher glucose transporter 1
      (GLUT1) expression (and glucose transport activity) vs MHS rats, diabetic and
      nondiabetic MNS and MHS rats were followed for 6 months and mesangial cells
      derived from these animals were exposed to high glucose (HG) vs normal glucose
      (NG) conditions. RESULTS: Glomerular expression of GLUT1 protein and ECM and
      transforming growth factor-beta (TGF-beta) mRNA was significantly upregulated in
      diabetic vs nondiabetic MNS, but not MHS rats. Upon exposure to HG and/or TGF
      beta, mesangial cells from 1- and 8-month-old MNS rats showed higher glucose
      transport activity and GLUT1 membrane expression than those from age-matched MHS
      rats. Likewise, ECM and TGF-beta production increased more markedly in response
      to HG and/or TGF-beta in MNS vs MHS mesangial cells. CONCLUSIONS: These data
      indicate that susceptibility to diabetic glomerulopathy in MNS rats is associated
      with increased GLUT1-dependent glucose transport activity in response to
      hyperglycaemia and/or TGF-beta, which may amplify ECM overproduction. Conversely,
      the haemodynamic protection from glomerulosclerosis in MHS rats is associated
      with lack of upregulation of TGF-beta/GLUT1 axis, thus supporting the concept
      that this axis may represent the link between haemodynamic and metabolic
      mechanisms of injury.

PMID- 16449287
TI  - Is it time for spironolactone therapy in dialysis patients?

PMID- 16449288
TI  - Apoptosis and proliferation of cultured mesangial cells isolated from kidneys of
      rosiglitazone-treated pregnant diabetic rats.
AB  - BACKGROUND: The peroxisome proliferator activating nuclear receptors (PPAR) are
      activated in the context of inflammation, diabetes or normal pregnancy. Renal
      mesangial cells express PPAR-gamma which upon activation are capable of exerting
      anti-inflammatory effects. We investigated the effect of in vivo treatment by
      rosiglitazone on angiotensin II (A-II) stimulated manifestations of inflammation
      in cultured renal mesangial cells, such as proliferation, apoptosis, TGF-beta1
      production and nuclear factor kappaB (NF-kappaB) activation, in the situation of
      pregnancies, complicated or not with diabetes. METHODS: Mesangial cells were
      isolated from the following groups, receiving or not 5 mg/kg rosiglitazone for 20
      days: normal controls, normal pregnant rats, those with streptozotocine induced
      diabetes and pregnant diabetic rats. Proliferation was assessed by 3H-thymidine
      incorporation. Apoptosis was evaluated by TUNEL assay. AT-1/AT-2 receptor density
      was assessed by 125I-AT-2 labelling, TGF-beta and NF-kappaB by specific ELISAs.
      RESULTS: Rosiglitazone pretreatment resulted in significantly decreased
      proliferation, apoptosis and reduced responsiveness to A-II stimulation in
      cultures from controls, pregnant rats and non-pregnant diabetic animals. In the
      pregnant diabetic group which received rosiglitazone prior to sacrifice,
      responsiveness to A-II was completely blunted. Moderate attenuation of TGF-beta
      synthesis and significant decrease in the levels of NF-kappaB in mesangial cell
      nuclei were observed in all rosiglitazone treated groups. CONCLUSIONS: PPAR-gamma
      activation by rosiglitazone resulted in decreased manifestation of inflammatory
      hallmarks, including inhibition of mesangial cell proliferation, downregulation
      of apoptosis and blunted responsiveness to A-II. These anti-inflammatory
      renoprotective effects were maximally expressed in cultures from pregnant
      diabetic animals. The therapeutic relevance of these observations is a matter of
      further investigations.

PMID- 16449289
TI  - Novel compound heterozygote mutations (H234Q/R1206X) of the ADAMTS13 gene in an
      adult patient with Upshaw-Schulman syndrome showing predominant episodes of
      repeated acute renal failure.
AB  - BACKGROUND: Unlike acquired thrombotic thrombocytopenic purpura or haemolytic
      uraemic syndrome, which are often intractable, thrombotic microangiopathy in
      patients with Upshaw-Schulman syndrome (USS)--a congenital deficiency of von
      Willebrand factor-cleaving protease (ADAMTS13) activity--responds very well to
      plasma infusion and does not even require plasma exchange. However, the symptoms
      significantly vary in each individual and thus clinicians often overlook this
      diagnosis. METHODS: A 31-year-old adult male patient with thrombotic
      microangiopathy, which was complicated with repeated episodes of acute renal
      failure, is reported. We suspected that the patient had USS and performed assays
      of ADAMT13 activity and its inhibitor, followed by ADAMTS13 gene analysis of the
      patient and his parents. RESULTS: The patient had extremely low ADAMTS13 activity
      and has no inhibitors of ADAMTS13. Through an ADAMTS13 gene analysis of this
      family, we found two novel mutations responsible for the disease: a missense
      mutation in exon 7 [702 C --> A (H234Q)] from the father and a nonsense mutation
      in exon 26 [3616 C --> T (R1206X)] from the mother. CONCLUSIONS: Our experience
      appears to indicate the importance of assays of ADAMTS13 activity and its
      inhibitor in patients who have episodes of renal insufficiency in association
      with thrombotic microangiopathy, for diagnosis and choice of treatment.

PMID- 16449290
TI  - Norepinephrine-induced vasoconstriction results in decreased blood volume in
      dialysis patients.
AB  - BACKGROUND: Hypotension during haemodialysis results from an inadequate
      cardiovascular response to ultrafiltration-induced hypovolaemia. It has been
      suggested that plasma volume could be increased as a result of systemic
      vasoconstriction. METHODS: We studied the effect of a norepinephrine (NOR)
      infusion (30 min), compared with no infusion, on relative blood volume (RBV) in
      six haemodialysis patients. During infusion we measured RBV, systolic blood
      pressure (SAP), heart rate (HR), stroke volume index (SI), total peripheral
      resistance (TPRI), ejection fraction (EF), inferior vena cava diameter (VCD) and
      core temperature. RESULTS: At the end of the NOR infusion, we observed a
      significant increase in TPRI (47+/-47% vs 4+/-17%; P<0.01) and SAP (27+/-12% vs
      0+/-8%; P<0.01). Norepinephrine-induced vasoconstriction resulted in a
      significant decrease in RBV (-9+/-3% vs 0+/-1%; P<0.01). No significant changes
      were seen in SI (-4+/-21% vs 0+/-8%), HR (-5+/-19% vs -4+/-5%), EF (7+/-14% vs 
      2+/-10%), VCD or temperature. CONCLUSIONS: We conclude that norepinephrine
      induced vasoconstriction results in a decrease in RBV. This indicates that
      improved haemodynamic stability during haemodialysis through vasoconstriction can
      be accompanied by a decrease in RBV and that part of the variability in blood
      volume may be due to changes in arterial tone. Such changes must be taken into
      account if RBV measurements are used to improve the haemodynamic tolerance of
      dialysis.

PMID- 16449291
TI  - Renal recovery from acute tubular necrosis requiring renal replacement therapy: a
      prospective study in critically ill patients.
AB  - BACKGROUND: Data on the incidence of end-stage renal disease (ESRD) resulting
      from irreversible acute tubular necrosis (ATN) are controversial. This
      prospective cohort study was designed to assess the need for short- and long-term
      dialysis in critically ill patients with severe ATN and to define risk factors
      for lack of renal recovery. METHODS: 433 consecutive patients with clinically
      diagnosed severe ATN necessitating renal replacement therapy were enrolled. Eight
      patients were excluded because renal biopsy revealed another cause of acute renal
      failure. None of the remaining 425 patients had pre-existing chronic renal
      insufficiency. Primary outcome criteria were recovery of renal function at
      discharge and ESRD status at 1 year follow-up. RESULTS: The overall in-hospital
      mortality of the cohort was 47%. At discharge, 57% of the 226 surviving patients
      had normal renal function, 33% had mild to moderate renal failure (serum
      creatinine: 1.3-3 mg/dl) and 10% had severe renal failure (serum creatinine: 3-6
      mg/dl). Multivariate analysis showed that neither patient characteristics (age,
      gender, comorbid conditions), severity of illness (APACHE III, number of failed
      organs) nor mode and duration of renal replacement therapy were related to
      recovery of renal function. After 1 year, 76 of the surviving patients had died
      and in one patient chronic renal failure had progressed to ESRD. CONCLUSIONS: If
      critically ill patients with normal renal function prior to the renal insults
      survive the precipitating cause of ATN, the overwhelming majority will recover
      sufficient renal function.

PMID- 16449292
TI  - Distal renal tubular acidosis in association with HIV infection and AIDS.

PMID- 16449293
TI  - Tunnelled haemodialysis catheter bacteraemia: risk factors for bacteraemia
      recurrence, infectious complications and mortality.
AB  - BACKGROUND: Infection is a serious complication of tunnelled cuffed catheter
      (TCC) use and is associated with high complication and mortality rates. Although
      attempts at TCC salvage after bacteraemia have been associated with high rates of
      recurrent bacteraemia, there have been no large studies in which multivariate
      analysis has been performed to control for confounding factors such as infecting
      organisms, diabetes, etc. METHODS: A prospective observational study was
      performed in chronic HD patients dialyzing with a TCC at seven outpatient HD
      centers. All patients diagnosed with TCC bacteraemia were observed for 3 months
      following initial presentation and outcomes were recorded. RESULTS: During the
      2.5 year study period, 226 patients had an episode of TCC bacteraemia that met
      inclusion criteria, and 3 month follow-up data were available in 219 episodes.
      Treatment failure, defined as recurrent TCC bacteraemia with the same organism or
      death from sepsis, occurred in 26 patients (12%). Infectious complications (such
      as endocarditis, osteomyelitis, etc.) occurred in 16 patients (7%), bacteraemia
      with a different organism occurred in 19 patients (9%), and death from sepsis
      occurred in eight patients (4%). Significant predictors of treatment failure (by
      univariate analysis) were TCC salvage, and infection with Staphylococcus aureus,
      (OR = 4.2, P = 0.002; and OR = 3.3, P = 0.02, respectively). TCC salvage, when
      used in episodes of S. aureus bacteraemia, was associated with an 8-fold higher
      risk of treatment failure (P = 0.001). The presence of an abnormal TCC exit site
      was associated with a significantly higher rate of death from sepsis, (OR = 7, P
      = 0.001). Outcomes (treatment failure and infectious complications) did not
      differ among bacteraemic episodes where the TCC was exchanged over a guidewire
      compared to those in which the TCC was immediately removed followed by delayed
      reinsertion. In the multivariate analysis, adjusted for potential confounding
      covariates, the only significant predictors of treatment failure after an episode
      of TCC bacteraemia were TCC salvage (OR = 5.4, P = 0.003), and S. aureus (OR =
      4.2, P = 0.002). In a multivariate analysis, controlling for TCC management, the
      only variable that was significantly associated with the development of an
      infectious complication was infection with S. aureus (OR = 3.5, P = 0.02).
      CONCLUSIONS: We have shown, using multivariate analysis and adjusting for
      potential confounding factors, that the use of TCC salvage and S. aureus are
      independent risk factors for treatment failure after an episode of TCC
      bacteraemia, and that S. aureus is an independent risk factor for developing an
      infectious complication. An infected-appearing TCC exit site is associated with a
      higher mortality rate. Episodes of TCC bacteraemia treated using TCC salvage are
      associated with the highest treatment failure rates. TCC guidewire exchange can
      be an acceptable practice, unless severe exit site or tunnel infection is
      present.

PMID- 16449295
TI  - Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and
      uterus: implications for expression, regulation, and cellular function.
AB  - Progesterone and its interaction with nuclear progesterone receptors (PR) PR-A
      and PR-B play a critical role in the regulation of female reproductive function
      in all mammals. However, our knowledge of the regulation and possible cellular
      function of PR protein isoforms in the fallopian tube and uterus in vivo is still
      very limited. In the present study, we revealed that equine chorionic
      gonadotropin (eCG) treatment resulted in a time-dependent increase in expression
      of both isoforms, reaching a maximal level at 48 h in the fallopian tube.
      Regulation of PR-A protein expression paralleled that of PR-B protein expression.
      However, in the uterus PR-B protein levels increased and peaked earlier than PR-A
      protein levels after eCG treatment. With prolonged exposure to eCG, PR-B protein
      levels decreased, whereas PR-A protein levels continued to increase. Furthermore,
      subsequent treatment with human (h)CG decreased the levels of PR protein isoforms
      in both tissues in parallel with increased endogenous serum progesterone levels.
      To further elucidate whether progesterone regulates PR protein isoforms, we
      demonstrated that a time-dependent treatment with progesterone (P(4)) decreased
      the expression of PR protein isoforms in both tissues, whereas decreases in p27,
      cyclin D(2), and proliferating cell nuclear antigen protein levels were observed
      only in the uterus. To define the potential PR-mediated effects on apoptosis, we
      demonstrated that the PR antagonist treatment increased the levels of PR protein
      isoforms, induced mitochondrial-associated apoptosis, and decreased in epidermal
      growth factor (EGF) and EGF receptor protein expression in both tissues.
      Interestingly, immunohistochemistry indicated that the induction of apoptosis by
      PR antagonists was predominant in the epithelium, whereas increase in PR protein
      expression was observed in stromal cells of both tissues. Taken together, these
      observations suggest that 1) the tissue-specific and hormonal regulation of PR
      isoform expression in mouse fallopian tube and uterus, where they are potentially
      involved in regulation of mitochondrial-mediated apoptosis depending on the
      cellular compartment; and 2) a possible interaction between functional PR protein
      and growth factor signaling may have a coordinated role for regulating apoptotic
      process in both tissues in vivo.

PMID- 16449294
TI  - Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency
      and after streptozotocin-induced diabetes in mouse pancreas.
AB  - We have recently reported that Pdx1-Cre-mediated whole pancreas inactivation of
      IGF-I gene [in pancreatic-specific IGF-I gene-deficient (PID) mice] results in
      increased beta-cell mass and significant protection against both type 1 and type
      2 diabetes. Because the phenotype is unlikely a direct consequence of IGF-I
      deficiency, the present study was designed to explore possible activation of
      proislet factors in PID mice by using a whole genome DNA microarray. As a result,
      multiple members of the Reg family genes (Reg2, -3alpha, and -3beta, previously
      not known to promote islet cell growth) were significantly upregulated in the
      pancreas. This finding was subsequently confirmed by Northern blot and/or real
      time PCR, which exhibited 2- to 8-fold increases in the levels of these mRNAs.
      Interestingly, these Reg family genes were also activated after streptozotocin
      induced beta-cell damage and diabetes (wild-type T1D mice) when islet cells were
      undergoing regeneration. Immunohistochemistry revealed increased Reg proteins in
      exocrine as well as endocrine pancreas and suggested their potential role in beta
      cell neogenesis in PID or T1D mice. Previously, other Reg proteins (Reg1 and
      islet neogenesis-associated protein) have been shown to promote islet cell
      replication and neogenesis. These uncharacterized Reg proteins may play a similar
      but more potent role, not only in normal islet cell growth in PID mice, but also
      in islet cell regeneration after T1D.

PMID- 16449296
TI  - Exercise training and calorie restriction increase SREBP-1 expression and
      intramuscular triglyceride in skeletal muscle.
AB  - Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated
      with obesity and type 2 diabetes (T2DM) and is thought to be related to insulin
      resistance (IR). Curiously, despite enhanced skeletal muscle insulin sensitivity,
      highly trained athletes and calorie-restricted (CR) monkeys also have increased
      IMTG. Sterol regulatory element-binding proteins (SREBPs) are transcription
      factors that regulate the biosynthesis of cholesterol and fatty acids. SREBP-1 is
      increased by insulin in skeletal muscle in vitro and in skeletal muscle of IR
      subjects, but SREBP-1 expression has not been examined in exercise training or
      calorie restriction. We examined the relationship between IMTG and SREBP-1
      expression in animal models of exercise and calorie restriction. Gastrocnemius
      and soleus muscle biopsies were obtained from 38 Sprague-Dawley rats (18 control
      and 20 exercise trained). Triglyceride content was higher in the gastrocnemius
      and soleus muscles of the trained rats. SREBP-1c mRNA, SREBP-1 precursor and
      mature proteins, and fatty acid synthase (FAS) protein were increased with
      exercise training. Monkeys (Macaca mulatta) were CR for a mean of 10.4 years,
      preventing weight gain and IR. Vastus lateralis muscle was obtained from 12
      monkeys (6 CR and 6 controls). SREBP-1 precursor and mature proteins and FAS
      protein were higher in the CR monkeys. In addition, phosphorylation of ERK1/ERK2
      was increased in skeletal muscle of CR animals. In summary, SREBP-1 protein and
      SREBP-1c mRNA are increased in interventions that increase IMTG despite enhanced
      insulin sensitivity. CR and exercise-induced augmentation of SREBP-1 expression
      may be responsible for the increased IMTG seen in skeletal muscle of highly
      conditioned athletes.

PMID- 16449297
TI  - Glucocorticoid-deficient corticotropin-releasing hormone knockout mice maintain
      glucose requirements but not autonomic responses during repeated hypoglycemia.
AB  - Glucocorticoids have been implicated in hypoglycemia-induced autonomic failure
      but also contribute to normal counterregulation. To determine the influence of
      normal and hypoglycemia-induced levels of glucocorticoids on counterregulatory
      responses to acute and repeated hypoglycemia, we compared plasma catecholamines,
      corticosterone, glucagon, and glucose requirements in male wild-type (WT) and
      glucocorticoid-deficient, corticotropin-releasing hormone knockout (CRH KO) mice.
      Conscious, chronically cannulated, unrestrained WT and CRH KO mice underwent a
      euglycemic (Prior Eu) or hypoglycemic clamp (Prior Hypo) on day 1 followed by a
      hypoglycemic clamp on day 2 (blood glucose both days, 65 +/- 1 mg/dl). Baseline
      epinephrine and glucagon were similar, and norepinephrine was elevated, in CRH KO
      vs. WT mice. CRH KO corticosterone was almost undetectable (<1.5 microg/dl) and
      unresponsive to hypoglycemia. CRH KO glucose requirements were significantly
      higher during day 1 hypoglycemia despite epinephrine and glucagon responses that
      were comparable to or greater than those in WT. Hyperinsulinemic euglycemia did
      not increase hormones or glucose requirements above baseline. On day 2, Prior
      Hypo WT had significantly higher glucose requirements and significantly lower
      corticosterone and glucagon responses. Prior Hypo and Prior Eu CRH KO mice had
      similar day 2 glucose requirements. However, Prior Hypo CRH KO mice had
      significantly lower day 2 epinephrine and norepinephrine vs. Prior Eu CRH KO and
      tended to have lower glucagon than on day 1. We conclude that glucocorticoid
      insufficiency in CRH KO mice correlates with 1) impaired counterregulation during
      acute hypoglycemia and 2) complex effects after repeated hypoglycemia, neither
      preventing decreased hormone responses nor worsening glucose requirements.

PMID- 16449299
TI  - Glucose metabolic adaptations in the intrauterine growth-restricted adult female
      rat offspring.
AB  - We studied glucose metabolic adaptations in the intrauterine growth-restricted
      (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming.
      Glucose futile cycling (GFC), which is altered when there is imbalance between
      glucose production and utilization, was studied during a glucose tolerance test
      (GTT) in 2-day-old (n = 8), 2-mo-old (n = 22), and 15-mo-old (n = 22) female rat
      offspring. The IUGR rats exposed to either prenatal (CM/SP, n = 5 per age),
      postnatal (SM/CP, n = 6), or pre- and postnatal (SM/SP, n = 6) nutrient
      restriction were compared with age-matched controls (CM/CP, n = 5). At 2 days,
      IUGR pups (SP) were smaller and glucose intolerant and had increased hepatic
      glucose production and increased glucose disposal (P < 0.01) compared with
      controls (CP). At 2 mo, the GTT, glucose clearance, and GFC did not change.
      However, a decline in hepatic glucose-6-phosphatase (P < 0.05) and fructose-1,6
      biphosphatase (P < 0.05) enzyme activities in the IUGR offspring was detected. At
      15 mo, prenatal nutrient restriction (CM/SP) resulted in greater weight gain (P <
      0.01) and hyperinsulinemia (P < 0.001) compared with postnatal nutrient
      restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in
      both the prenatal (CM/SP, P < 0.01) and postnatal calorie (SM/CP, P < 0.03) and
      growth-restricted offspring. The IUGR offspring with pre- and postnatal nutrient
      restriction (SM/SP) were smaller, hypoinsulinemic (P < 0.03), and hypoleptinemic
      (P < 0.03), with no change in GTT, hepatic glucose production, GFC, or glucose
      clearance. We conclude that there is pre- and postnatal programming that affects
      the postnatal compensatory adaptation of GFC and disposal initiated by changes in
      circulating insulin concentrations, thereby determining hepatic insulin
      sensitivity in a phenotype-specific manner.

PMID- 16449298
TI  - Computational model of in vivo human energy metabolism during semistarvation and
      refeeding.
AB  - Changes in body weight and composition are the result of complex interactions
      among metabolic fluxes contributing to macronutrient balances. To better
      understand these interactions, a mathematical model was constructed that used the
      measured dietary macronutrient intake during semistarvation and refeeding as
      model inputs and computed whole body energy expenditure, de novo lipogenesis, and
      gluconeogenesis as well as turnover and oxidation of carbohydrate, fat, and
      protein. Published in vivo human data provided the basis for the model components
      that were integrated by fitting a few unknown parameters to the classic Minnesota
      human starvation experiment. The model simulated the measured body weight and fat
      mass changes during semistarvation and refeeding and predicted the unmeasured
      metabolic fluxes underlying the body composition changes. The resting metabolic
      rate matched the experimental measurements and required a model of adaptive
      thermogenesis. Refeeding caused an elevation of de novo lipogenesis that, along
      with increased fat intake, resulted in a rapid repletion and overshoot of body
      fat. By continuing the computer simulation with the prestarvation diet and
      physical activity, the original body weight and composition were eventually
      restored, but body fat mass was predicted to take more than one additional year
      to return to within 5% of its original value. The model was validated by
      simulating a recently published short-term caloric restriction experiment without
      changing the model parameters. The predicted changes in body weight, fat mass,
      resting metabolic rate, and nitrogen balance matched the experimental
      measurements, thereby providing support for the validity of the model.

PMID- 16449300
TI  - Perturbed skeletal muscle insulin signaling in the adult female intrauterine
      growth-restricted rat.
AB  - To determine the molecular mechanism(s) linking fetal adaptations in intrauterine
      growth restriction (IUGR) to adult maladaptations of type 2 diabetes mellitus, we
      investigated the effect of prenatal seminutrient restriction, modified by early
      postnatal ad libitum access to nutrients (CM/SP) or seminutrient restriction
      (SM/SP), vs. early postnatal seminutrient restriction alone (SM/CP) or control
      nutrition (CM/CP) on the skeletal muscle postreceptor insulin-signaling pathway
      in the adult offspring. The altered in utero hormonal/metabolic milieu was
      associated with no change in basal total IRS-1, p85, and p110beta subunits of PI
      3-kinase, PKCtheta, and PKCzeta concentrations but an increase in basal IRS-2 (P
      < 0.05) only in the CM/SP group and an increase in basal phospho (p)-PDK-1 (P <
      0.05), p-Akt (P < 0.05), and p-PKCzeta (P < 0.05) concentrations in the CM/SP and
      SM/SP groups. Insulin-stimulated increases in p-PDK-1 (P < 0.05) and p-Akt (P <
      0.0007), with no increase in p-PKCzeta, were seen in both CM/SP and SM/SP groups.
      SHP2 (P < 0.03) and PTP1B (P < 0.03) increased only in SM/SP with no change in
      PTEN in CM/SP and SM/SP groups. Aberrations in kinase and phosphatase moieties in
      the adult IUGR offspring were initiated in utero but further sculpted by the
      early postnatal nutritional state. Although the CM/SP group demonstrated enhanced
      kinase activation, the SM/SP group revealed an added increase in phosphatase
      concentrations with the net result of heightened basal insulin sensitivity in
      both groups. The inability to further respond to exogenous insulin was due to the
      key molecular distal roadblock consisting of resistance to phosphorylate and
      activate PKCzeta necessary for GLUT4 translocation. This protective adaptation
      may become maladaptive and serve as a forerunner for gestational and type 2
      diabetes mellitus.

PMID- 16449301
TI  - In vivo measurement of synthesis rate of multiple plasma proteins in humans.
AB  - Advances in quantitative proteomics have facilitated the measurement of large
      scale protein quantification, which represents net changes in protein synthesis
      and breakdown. However, measuring the rate of protein synthesis is the only way
      to determine the translational rate of gene transcripts. Here, we report a
      technique to measure the rate of incorporation of amino acids from ingested
      protein labeled with stable isotope into individual plasma proteins. This
      approach involves three steps: 1) production of stable isotope-labeled milk whey
      protein, oral administration of this intrinsically labeled protein, and
      subsequent collection of blood samples; 2) fractionation of the plasma and
      separation of the individual plasma proteins by a combination of anion exchange
      high-pressure liquid chromatography and gel electrophoresis; and 3)
      identification of individual plasma proteins by tandem mass spectrometry and
      measurement of stable isotopic enrichment of these proteins by gas chromatography
      mass spectrometry. This method allowed the measurement of the fractional
      synthesis rate (FSR) of 29 different plasma proteins by using the same precursor
      pool. We noted a 30-fold difference in FSR of different plasma proteins with a
      wide range of physiological functions. This approach offers a tremendous
      opportunity to study the regulation of plasma proteins in humans in many
      physiological and pathological states.

PMID- 16449302
TI  - Acute, same-day effects of antecedent exercise on counterregulatory responses to
      subsequent hypoglycemia in type 1 diabetes mellitus.
AB  - Exercise-induced hypoglycemia can occur within hours after exercise in type 1
      diabetes mellitus (T1DM) patients. This study tested the hypothesis that an acute
      exercise bout causes (within hours) blunted autonomic and metabolic responses to
      subsequent hypoglycemia in patients with T1DM. Twelve T1DM patients (3 W/9 M)
      were studied during a single-step, 2-h hyperinsulinemic (572 +/- 4 pmol/l)
      hypoglycemic (2.8 +/- 0.1 mmol/l) clamp 2 h after either a hyperinsulinemic
      euglycemic (AM EUG) or hypoglycemic clamp (AM HYPO) or after sitting in a chair
      with basal insulin infusion (AM CON) or 90 min of moderate-intensity exercise
      (50% Vo(2 max), AM EX). Both AM HYPO and AM EX significantly blunted epinephrine
      responses and muscle sympathetic nerve activity responses to subsequent
      hypoglycemia compared with both control groups. Endogenous glucose production was
      significantly lower and the exogenous glucose infusion rate needed to maintain
      the hypoglycemic level was significantly greater during subsequent hypoglycemia
      in AM EX vs. CON. Rate of glucose disposal (Rd) was significantly reduced
      following AM HYPO. In summary, within 2.5 h, both moderate-intensity AM EX and AM
      HYPO blunted key autonomic counterregulatory responses. Despite this, glucose Rd
      was reduced during afternoon hypoglycemia following morning hypoglycemia,
      indicating posthypoglycemic insulin resistance. After morning exercise,
      endogenous glucose production was blunted, but glucose Rd was maintained during
      afternoon hypoglycemia, thereby indicating reduced metabolic defenses against
      hypoglycemia. These data suggest that exercise-induced counterregulatory failure
      can occur very rapidly, increasing the risk for hypoglycemia in T1DM within
      hours.

PMID- 16449303
TI  - Pathogenic role of Fgf23 in Hyp mice.
AB  - Inactivating mutations of the PHEX (phosphate-regulating gene with homologies to
      endopeptidases on the X chromosome) endopeptidase, the disease-causing gene in X
      linked hypophosphatemia (XLH), results in increased circulating levels of
      fibroblastic growth factor-23 (FGF23), a bone-derived phosphaturic factor. To
      determine the causal role of FGF23 in XLH, we generated a combined Fgf23
      deficient enhanced green fluorescent protein (eGFP) reporter and Phex-deficient
      Hyp mouse model (Fgf23(+/-)/Hyp). eGFP expression was expressed in osteocytes
      embedded in bone that exhibited marked upregulation of eGFP in response to Phex
      deficiency and in CD31-positive cells in bone marrow venules that expressed low
      eGFP levels independently of Phex. In bone marrow stromal cells (BMSCs) derived
      from Fgf23(-/-)/Hyp mice, eGFP expression was also selectively increased in
      osteocyte-like cells within mineralization nodules and detected in low levels in
      CD31-positive cells. Surprisingly, eGFP expression was not increased in cell
      surface osteoblasts, indicating that Phex deficiency is necessary but not
      sufficient for increased Fgf23 expression in the osteoblast lineage. Additional
      factors, associated with either osteocyte differentiation and/or extracellular
      matrix, are necessary for Phex deficiency to stimulate Fgf23 gene transcription
      in bone. Regardless, the deletion of Fgf23 from Hyp mice reversed the
      hypophosphatemia, abnormal 1,25(OH)(2)D(3) levels, rickets, and osteomalacia
      associated with Phex deficiency. These results suggest that Fgf23 acts downstream
      of Phex to cause both the renal and bone phenotypes in Hyp mice.

PMID- 16449304
TI  - Fluconazole for the management of invasive candidiasis: where do we stand after
      15 years?
AB  - Candida spp. are responsible for most of the fungal infections in humans.
      Available since 1990, fluconazole is well established as a leading drug in the
      setting of prevention and treatment of mucosal and invasive candidiasis.
      Fluconazole displays predictable pharmacokinetics and an excellent tolerance
      profile in all groups, including the elderly and children. Fluconazole is a
      fungistatic drug against yeasts and lacks activity against moulds. Candida krusei
      is intrinsically resistant to fluconazole, and other species, notably Candida
      glabrata, often manifest reduced susceptibility. Emergence of azole-resistant
      strains as well as discovery of new antifungal drugs (new triazoles and
      echinocandins) have raised important questions about its use as a first line
      drug. The aim of this review is to summarize the main available data on the
      position of fluconazole in the prophylaxis or curative treatment of invasive
      Candida spp. infections. Fluconazole is still a major drug for antifungal
      prophylaxis in the setting of transplantation (solid organ and bone marrow),
      intensive care unit, and in neutropenic patients. Prophylactic fluconazole still
      has a place in HIV-positive patients in viro-immunological failure with recurrent
      mucosal candidiasis. Fluconazole can be used in adult neutropenic patients with
      systemic candidiasis, as long as the species identified is a priori susceptible.
      Among non-neutropenic patients with candidaemia fluconazole is one of the first
      line drugs for susceptible species. Cases reports and uncontrolled studies have
      also reported its efficacy in the setting of osteoarthritis, endophthalmitis,
      meningitis, endocarditis and peritonitis caused by Candida spp. among
      immunocompetent adults. In paediatrics, fluconazole is a well tolerated and major
      prophylactic drug for high-risk neonates, as well as an alternative treatment for
      neonatal candidiasis. Importantly 15 years after its introduction in the
      antifungal armamentarium, fluconazole is still a first line treatment option in
      several cases of invasive candidiasis. Its prophylactic use should however be
      limited to selected high-risk patients to limit the risk of emergence of azole
      resistant strains.

PMID- 16449305
TI  - Diversity and evolution of blaZ from Staphylococcus aureus and coagulase-negative
      staphylococci.
AB  - OBJECTIVES: To elucidate the diversity and evolutionary history of plasmid- and
      chromosomally-located blaZ, to detect indications of frequent exchange of blaZ
      between human and bovine staphylococci and to estimate the frequency of transfer
      of blaZ between coagulase-negative staphylococci (CoNS) and Staphylococcus aureus
      of bovine origin. METHODS: blaZ was detected in 143 strains of penicillin
      resistant S. aureus and CoNS from five Danish cattle herds (n = 25/23), random
      CoNS isolates from Denmark (n = 37), a collection of S. aureus from six different
      countries (n = 52), humans in Denmark (n = 3) and beta-lactamase control strains
      (n = 3). The sequence was determined in 105 strains and compared to published
      sequences by pairwise and multiple alignments. Maximum likelihood analysis was
      performed including bootstrap analysis. Parsimony, neighbour joining and
      consensus comparisons were performed for recombination. The localization of blaZ
      was determined by Southern blotting in 108 isolates. RESULTS: All penicillin
      resistant strains carried blaZ and showed a similar organization of blaR1 and
      blaZ. The blaZ gene was localized to a plasmid in only 16 of the resistant
      strains. Sixty-nine sequences representing 105 isolates and sequences retrieved
      from public databases were compared. A phylogenetic tree showed that blaZ exists
      in three evolutionary lines: one group was of plasmid origin, one group was of
      chromosomal origin and one intermediate group. Sixty-nine sequence types were
      demonstrated. They translated into 11 BlaZ protein types. The major types all
      contained strains of both human and bovine origin, and more than one
      Staphylococcus species, demonstrating a shared gene pool. In a comparison of S.
      aureus and CoNS obtained from five Danish cattle herds, the same type of blaZ was
      only detected in one case. CONCLUSIONS: Results indicated a separate evolution
      for plasmid- and chromosomally-encoded blaZ. Although a common gene pool seems to
      exist among staphylococci, exchange of blaZ between strains and species is judged
      to be an extremely rare event.

PMID- 16449306
TI  - Factors associated with adherence to infectious diseases advice in two intensive
      care units.
AB  - OBJECTIVES: Several studies have reported that infectious diseases (ID)
      consultations improve the quality of antibiotic prescription, providing adherence
      is adequate. The aim of this study is to determine the factors associated with
      adherence to such therapeutic advice. PATIENTS AND METHODS: We conducted a
      prospective study in two intensive care units (ICUs) over a 6 month period.
      Systematic bedside diagnostic and therapeutic ID advice was delivered for all
      patients receiving antibiotic therapy. RESULTS: A total of 381 consultations for
      195 patients were recorded, 244 (64%) in ward A and 137 (36%) in ward B. The
      median SAPS score was 45 and the mortality rate was 23%. Infections accounted for
      220 (58%) admissions. A diagnostic discrepancy between ID and intensive care
      specialists was noted in 125 (33%) cases. The ID specialist advised continuation
      of the same antibiotic therapy in 138 (36%) cases, a change in 154 (41%) and
      withdrawal in 89 (23%). Adherence to ID therapeutic advice was recorded for 326
      (86%) cases. Multivariate analysis identified two factors independently
      associated with adherence: ward B [odds ratio (OR), 4.9; 95% confidence interval
      (CI), 2.0-12.1] and proposition to pursue the same therapy (OR, 4.8; 95% CI, 1.6
      14.5). CONCLUSIONS: Patients' characteristics and antibiotic therapy modalities
      do not influence adherence to ID consultation. In contrast, the ward and its
      characteristics play a major role in adherence to ID advice.

PMID- 16449307
TI  - The surprising optimist: why Tom Daschle believes that the country is ready for
      comprehensive health reform. Interview by Robert Galvin.
AB  - When Tom Daschle was last a private citizen, Jimmy Carter was president, and the
      country was embroiled in a debate about how to control health care costs. After a
      distinguished twenty-six-year career in Congress, Daschle has a lot to say about
      not only health care costs but overall system reform. With his deep understanding
      of the inner workings of Congress, Daschle breaks from the prevailing belief that
      incrementalism is the right approach; comments on the novel use of budget
      reconciliation to pass reform; and argues that the country, including some
      business leaders, is ready for comprehensive change with a bigger role for
      government.

PMID- 16449308
TI  - Obstetric and perinatal outcome and preliminary results of development of
      children born after in vitro maturation of oocytes.
AB  - BACKGROUND: Careful follow-up of children born after in vitro maturation (IVM) of
      human oocytes is essential because the technique is still very new. METHODS:
      Obstetric and perinatal data were collected from all deliveries after IVM
      treatment during 1999-2004. The growth and development of IVM children was
      assessed at 6, 12 and 24 months using Muenchener Funktionelle Entwicklungs
      Diagnostik and Bayley Scales of Infants. RESULTS: In total, 43 women [age 31.2 +/
      3.9 (mean +/- SD) years] gave birth to 40 singleton infants and three sets of
      twins (multiple rate 7.0%). Obstetric complications occurred in 15 pregnancies
      (35%). The mean birthweight of singleton infants was 3550 +/- 441 g and that of
      twins 2622 +/- 194 g. The rate of preterm birth infants was 5% in singletons. No
      perinatal deaths occurred. At the age of 12 months, eight children (19%)
      expressed minor developmental problems and one girl was found to have optical
      glioma. At 2 years of age, neuropsychological development was within the normal
      range. CONCLUSIONS: The obstetric and perinatal outcome was good, and the mean
      birthweight of the infants was normal. Minor developmental delay was
      overexpressed at 12 months, but the development of the children was normal at 2
      years.

PMID- 16449309
TI  - The role of endometrial and subendometrial vascularity measured by three
      dimensional power Doppler ultrasound in the prediction of pregnancy during frozen
      thawed embryo transfer cycles.
AB  - BACKGROUND: A good blood supply to the endometrium is usually considered as an
      essential requirement for implantation. OBJECTIVE: The aim of this study was to
      evaluate the role of endometrial and subendometrial vascularity in the prediction
      of pregnancy during frozen-thawed embryo transfer (FET) cycles. METHODS: Women
      undergoing FET in natural or clomiphene-induced cycles after the first stimulated
      IVF treatment were recruited. A three-dimensional (3D) ultrasound examination
      with power Doppler was performed 1 day after the LH surge to determine
      endometrial thickness, endometrial pattern, pulsatility index (PI) and resistance
      index (RI) of uterine vessels, endometrial volume, vascularization index, flow
      index and vascularization flow index of endometrial and subendometrial regions.
      RESULTS: Women in the pregnant group were significantly younger and used less
      gonadotrophins in their stimulated cycle. Endometrial thickness, endometrial
      volume, endometrial pattern, uterine PI, uterine RI, endometrial and
      subendometrial 3D power Doppler flow indices were similar between the nonpregnant
      and the pregnant groups. The age of women was the only predictive factor for
      pregnancy. Receiver operating characteristic curve analysis revealed that the
      area under the curve was around 0.5 for all ultrasound parameters for endometrial
      receptivity. CONCLUSION: Vascularity of endometrial and subendometrial layers
      measured by 3D power Doppler ultrasound is not a good predictor of pregnancy in
      FET cycles if measured at one time point only.

PMID- 16449310
TI  - A systematic review and meta-analysis of randomized controlled trials on
      metformin co-administration during gonadotrophin ovulation induction or IVF in
      women with polycystic ovary syndrome.
AB  - BACKGROUND: A systematic review of randomized controlled trials (RCTs) comparing
      whether metformin co-administration with gonadotrophins for ovulation induction
      (OI) with timed intercourse or IVF improves outcome in women with polycystic
      ovary syndrome (PCOS). METHODS: The quality of reporting of meta-analyses
      (QUOROM) guidelines were followed. A systematic computerized literature search of
      three bibliographic databases was performed. RESULTS: Eight RCTs were included in
      the overall review. Meta-analysis demonstrated that the co-administration of
      metformin to gonadotrophin OI does not significantly improve ovulation [odds
      ratio (OR) = 3.27; 95% confidence interval (95% CI) = 0.31-34.72] or pregnancy
      (OR = 3.46; 95% CI = 0.98-12.2) rates. Metformin co-administration to IVF
      treatment does not improve pregnancy (OR = 1.29; 95% CI = 0.84-1.98) or live
      birth (OR = 2.02, 95% CI = 0.98-4.14) rates but reduces the risk of ovarian
      hyperstimulation syndrome (OHSS) (OR = 0.21; 95% CI = 0.11-0.41, P < 0.00001).
      CONCLUSIONS: Current data on the use of metformin in the gonadotrophin OI or IVF
      treatment settings are inconclusive because of the review's failure to exclude an
      important clinical treatment effect. Further RCTs are necessary to definitively
      clarify whether metformin co-administration during gonadotrophin OI or IVF will
      improve the efficacy of these treatments in PCOS women.

PMID- 16449311
TI  - Human fetal ovarian culture permits meiotic progression and chromosome pairing
      process.
AB  - BACKGROUND: The female meiotic process seems to be crucial for aneuploidy in
      humans. The first stages of mammalian female meiosis take place during the fetal
      period. Therefore, only little is known about female meiosis. The goal of this
      study was to develop a culture technique that permits human oocytes to progress
      through meiotic prophase, to provide a system to study human female meiosis.
      METHOD: Fetal ovaries from four cases were cultured up to 35 days in alpha
      minimal essential medium, 2% human serum albumin, 5 microg/ml insulin, 5
      microg/ml transferrin, 5 ng/ml selenium and 100 IU/ml penicillin-100 microg/ml
      streptomycin. RESULTS AND CONCLUSIONS: Although ovarian response to culture
      conditions varied, human oocytes survived in vitro up to 5 weeks. In three cases,
      we observed significant variation in stages of meiosis among the cultures. The
      homologous chromosome pairing process was studied for the first time in cultured
      oocytes, and the results suggested that the pairing process was completed
      following the same features described previously for euploid oocytes, as followed
      by the chromosome-13 pairing process and synaptonemal complex formation. Although
      a higher proportion of degenerated oocytes were observed as culture time
      increased, we also observed oogonial entrance to meiotic prophase.

PMID- 16449312
TI  - Laparoscopic nerve-sparing complete excision of deep endometriosis: is it
      feasible?
AB  - BACKGROUND: Little is known about the morbidity associated with laparoscopic
      complete excision of endometriosis in terms of urinary, digestive and sexual
      function. METHODS: We performed a prospective non-randomized study in 45 patients
      with laparoscopic complete excision of all detectable foci of endometriosis with
      segmental bowel resection using a non nerve-sparing technique (control group
      group A n=20) and a nerve-sparing technique (case group-group B n=25). At initial
      gynaecological evaluation, and at follow-up details on dysmenorrhoea, pelvic
      pain, dyspareunia and dyschezia were evaluated using an interview-based
      questionnaire (10-point analogue rating scale: 0=absent, 10=unbearable). RESULTS:
      The mean (+/-SD) follow-up period was 15.3+/-10 months (range, 8.8-23 months) for
      group A and 3.5+/-2.1 months (range, 0.3-5.2 months) for group B. In the
      immediate postoperative course, in group A three women required blood transfusion
      vs seven women in group B (P=0.003). The median time to resume the voiding
      function was significantly shorter in group B (12.5 vs 3.0 days; P<0.01). At the
      time of follow-up a higher proportion of patients in group B were 'very
      satisfied' than those in group A (87.7% vs 59.0%, P=0.013). CONCLUSIONS:
      Laparoscopic nerve-sparing complete excision of endometriosis seems to be
      feasible and offers good results in terms of bladder morbidity reduction with
      apparently higher satisfaction than classical technique. Larger series with
      longer follow-up are needed to confirm our results.

PMID- 16449313
TI  - Membrane glucocorticoid receptors are down regulated by glucocorticoids in
      patients with systemic lupus erythematosus and use a caveolin-1-independent
      expression pathway.
AB  - BACKGROUND: Membrane-bound glucocorticoid receptors (mGCR) are up regulated on
      monocytes after in vitro stimulation and in patients with rheumatoid arthritis.
      Caveolin-1 is critical for the transport of plasma membrane oestrogen receptors
      to the cell surface. OBJECTIVES: To investigate the expression of mGCR in
      patients with systemic lupus erythematosus (SLE)-a disease with different
      aetiopathogenesis and treatment regimens-and to examine whether caveolin-1 is
      critical for the transport of mGCR to the cell surface. METHODS: Frequencies of
      mGCR+ peripheral blood mononuclear cells were measured using high-sensitivity
      immunofluorescent staining and tested for correlation with SLE disease activity
      and glucocorticoid treatment. Semiquantitative polymerase chain reaction,
      immunofluorescence, recombinant expression and confocal laser-scanning microscopy
      were used to search for an association of mGCR with caveolin-1. RESULTS: The
      frequencies of mGCR+ monocytes (CD14+) were considerably higher in patients with
      SLE (n = 33) than in healthy controls (n = 58), whereas B cells (CD19+) were not
      different in this regard. T cells (CD3+) were always mGCR-. The frequency of
      mGCR+ monocytes in patients with SLE did not correlate with disease activity, but
      did inversely correlate with glucocorticoid dosages; this inverse correlation was
      confirmed by corresponding in vitro experiments with stimulated monocytes. The
      induced up regulation of mGCR was not accompanied by an up regulation of caveolin
      1, and mGCR are not colocalised with caveolin-1 in plasma membrane caveolae.
      CONCLUSION: mGCR are (a) up regulated in patients with SLE and by inflammatory
      stimuli and (b) down regulated by glucocorticoids, suggesting a negative feedback
      loop to control glucocorticoid action. Drugs binding selectively to mGCR may in
      future prove to be of therapeutic value.

PMID- 16449314
TI  - Impact of anti-TNF treatment on growth in severe juvenile idiopathic arthritis.
AB  - OBJECTIVES: To evaluate the impact of anti-tumour necrosis factor (TNF) treatment
      on growth and to identify the predictors for the change in growth in severe
      juvenile idiopathic arthritis (JIA). METHODS: Data from 71 JIA patients (43 on
      etanercept, 28 on infliximab) were reviewed two years before and two years on the
      anti-TNF treatment. The patients had polyarticular disease course (48
      polyarthritis, 19 extended oligoarthritis, two systemic arthritis, and two
      enthesitis related arthritis). At the initiation of the anti-TNF treatment, their
      mean age was 9.6 years and the mean duration of JIA, 5.7 years. RESULTS: In the
      patients with delayed growth before anti-TNF treatment (n = 53), the growth
      velocity, measured as the change in height standard deviation score, accelerated
      +0.45 (95% confidence interval, 0.33 to 0.56) (p<0.001) during the anti-TNF
      treatment. In the patients with normal or accelerated growth before anti-TNF
      treatment (n = 18), the change in growth velocity was +0.05 (0.07 to 0.16) (p =
      0.39). At two years on anti-TNF treatment, the growth velocity between these two
      groups was similar. No difference was found between the patients treated with
      etanercept or infliximab. A decelerating growth rate before the anti-TNF
      treatment was the strongest predictor for the observed increase in the growth
      velocity. The change in the inflammatory activity remained a significant
      predictor of the growth velocity even after the decrease in glucocorticoid dose
      was taken into account. CONCLUSIONS: In the treatment of polyarticular JIA, the
      anti-TNF treatment not only suppresses inflammation but also restores growth
      velocity.

PMID- 16449315
TI  - Annexin A5 polymorphism (-1C-->T) and the presence of anti-annexin A5 antibodies
      in the antiphospholipid syndrome.
AB  - BACKGROUND: Annexin A5 is thought to have a role in the pathophysiology of the
      antiphospholipid syndrome (APS)-a syndrome characterised by recurrent thrombosis
      and pregnancy morbidity. OBJECTIVE: To investigate whether anti-annexin A5
      immunoglobulin (Ig)M or IgG antibodies, or the -1C-->T polymorphism of annexin
      A5, is a risk factor for thrombosis or miscarriage, and whether the -1C-->T
      polymorphism is correlated with APS. METHODS: A cohort study was carried out with
      a population of 198 patients with primary APS, systemic lupus erythematosus or
      lupus-like disease. For the detection of anti-annexin A5 antibodies and the
      measurement of annexin A5 plasma levels, ELISA-type methods were used. The
      annexin A5 -1C-->T mutation was detected by restriction fragment length
      polymorphism. RESULTS: 71 patients were positive for annexin A5 IgM or IgG
      antibodies, of whom 53 patients were positive for anti-annexin A5 IgG antibodies
      and 27 of 198 patients were positive for anti-annexin A5 IgM antibodies. The
      prevalence of IgM or IgG anti-annexin A5 antibodies was not significantly
      associated with thrombosis or miscarriage on multivariate analysis. The
      prevalence of the -1C-->T mutation in the annexin A5 gene (46/198 patients) was
      significantly associated with miscarriage (odds ratio 2.7, 95% confidence
      interval 1.1 to 6.7, independent risk factor). CONCLUSION: The detection of anti
      annexin A5 antibodies does not seem relevant for estimating the risk for
      thrombosis or miscarriage in APS. The -1C-->T mutation was an independent risk
      factor for miscarriage, which is independent of APS.

PMID- 16449316
TI  - Citrullinated fibrinogen detected as a soluble citrullinated autoantigen in
      rheumatoid arthritis synovial fluids.
AB  - BACKGROUND: Anti-citrullinated protein antibodies (ACPA) are specifically and
      frequently detected in sera of patients with rheumatoid arthritis (RA).
      Citrullinated fibrin or fibrinogen is a candidate autoantigen of such antibodies.
      OBJECTIVE: To investigate the presence of citrullinated fibrinogen (cFBG) in the
      plasma or synovial fluid of patients with RA and control patients, and to
      determine cFBG levels and their relationship with serum markers for RA if it is
      present. METHODS: A sandwich enzyme linked immunosorbent assay (ELISA) to measure
      cFBG was established using monoclonal antibodies cF16.1 and cF252.1, generated by
      immunising mice with R16Cit and R252Cit, the fibrinogen Aalpha chain derived
      sequences with citrulline at position 16 and 252, respectively, and the presence
      of cFBG was further investigated with immunoprecipitation-western blotting.
      RESULTS: Positive signals were detected in 11/15 RA synovial fluids (RASFs), but
      not in osteoarthritis synovial fluids or RA plasma with sandwich ELISA for cFBG
      using cF16.1 and an anti-modified citrulline (AMC) antibody. The presence of cFBG
      in RASFs was confirmed by immunoprecipitation-western blotting. Furthermore, most
      RA sera strongly reacted against R16Cit. No relationship was seen between RASF
      cFBG levels and C reactive protein or anti-cyclic citrullinated peptide antibody
      levels of the paired sera. CONCLUSION: cFBG is detected as a soluble
      citrullinated autoantigen in RASFs and may therefore be a genuine candidate
      antigen for ACPA in patients with RA.

PMID- 16449317
TI  - The role of MAP65-1 in microtubule bundling during Zinnia tracheary element
      formation.
AB  - The MAP65 family of microtubule-associated proteins performs various functions at
      different stages of the cell cycle and differentiation. In this study, we have
      investigated the synchronous transdifferentiation of Zinnia mesophyll cells into
      tracheary elements in vitro. This allowed us to examine the role of the
      microtubule-associated protein MAP65 during the characteristic bunching of
      cortical microtubules that underlie the developing ribs of secondarily thickened
      cell wall. Immunofluorescence confirmed the microtubule bundles to be decorated
      with anti-MAP65 antibodies. Three Zinnia MAP65 genes were examined; the
      expression of ZeMAP65-1 was found to match that of the differentiation marker
      TED2 and both were found to be upregulated upon addition of inductive hormones.
      We cloned the full-length sequence of ZeMAP65-1 and found it to be most similar
      to other MAP65 isoforms known to bundle microtubules in other plant species.
      However, not all MAP65 proteins crosslink cortical microtubules and so, to
      confirm its potential bundling capacity, ZeMAP65-1 was transiently overexpressed
      in Arabidopsis suspension cells. This resulted in the super-bundling of
      microtubules in patterns resembling those in differentiating xylem cells. These
      findings establish that the MAP65-1 group of proteins is responsible for the
      bundling of cortical microtubules during secondary cell wall formation of
      xylogenesis as well as during the expansion of primary cell walls.

PMID- 16449318
TI  - Connexin31 cannot functionally replace connexin43 during cardiac morphogenesis in
      mice.
AB  - In the gastrulating mouse embryo, the gap junction protein connexin43 is
      expressed exclusively in cells derived from the inner cell mass, whereas
      connexin31 is expressed in cells of the trophoblast lineage. Since connexin43 and
      connexin31 do not form heterotypic gap junction channels in exogenous expression
      systems, such as HeLa cells and Xenopus oocytes, previous studies have suggested
      that the incompatibility of these two connexins could contribute to the
      separation of connexin43-expressing and connexin31-expressing compartments
      between embryo and extraembryonic tissues at gastrulation, respectively. Thus, we
      have generated connexin43 knock-in connexin31 mice, in which the coding region of
      the connexin43 gene was replaced by that of connexin31. Interbreeding of
      heterozygous connexin43 knock-in connexin31 mice resulted in homozygous
      connexin43 knock-in connexin31 mice, but none of them survived to adulthood. As
      these mice were born at the expected Mendelian frequency, we conclude that the
      reported incompatibility of connexin43 and connexin31 to form heterotypic gap
      junction channels does not interfere with normal embryonic development. Neonatal
      homozygous connexin43 knock-in connexin31 hearts showed malformation in the
      subpulmonary outlet of the right ventricle, similar to general connexin43
      deficient mice. Electrocardiograms of neonatal hearts in homozygous connexin43
      knock-in connexin31 mice revealed significantly low voltage of the QRS complex.
      This is in contrast to previous results from our laboratory which showed that
      replacement of connexin43 by connexin40 resulted in morphologically and
      functionally normal hearts. We conclude that connexin31 cannot functionally
      replace connexin43 during cardiac morphogenesis.

PMID- 16449319
TI  - Par-1 kinase establishes cell polarity and functions in Notch signaling in the
      Drosophila embryo.
AB  - The Drosophila protein kinase Par-1 is expressed throughout Drosophila
      development, but its function has not been extensively characterized because of
      oocyte lethality of null mutants. In this report, we have characterized the
      function of Par-1 in embryonic and post-embryonic epithelia. Par-1 protein is
      dynamically localized during embryonic cell polarization, transiently restricted
      to the lateral membrane domain, followed by apicolateral localization. We
      depleted maternal and zygotic par-1 by RNAi and revealed a requirement for Par-1
      in establishing cell polarity. Par-1 restricts the coalescing adherens junction
      to an apicolateral position and prevents its widespread formation along the
      lateral domain. Par-1 also promotes the localization of lateral membrane proteins
      such as Delta. These activities are important for the further development of cell
      polarity during gastrulation. By contrast, Par-1 is not essential to maintain
      epithelial polarity once it has been established. However, it still has a
      maintenance role since overexpression causes severe polarity disruption.
      Additionally, we find a novel role for Par-1 in Notch signal transduction during
      embryonic neurogenesis and retina determination. Epistasis analysis indicates
      that Par-1 functions upstream of Notch and is critical for proper localization of
      the Notch ligand Delta.

PMID- 16449320
TI  - TGFbeta inhibition of yolk-sac-like differentiation of human embryonic stem-cell
      derived embryoid bodies illustrates differences between early mouse and human
      development.
AB  - Transforming growth factor beta (TGFbeta) plays an important role in development
      and maintenance of murine yolk sac vascular development. Targeted deletions of
      Tgfb1 and other components of this signaling pathway, such as Acvrl1, Tgfbr1 and
      Tgfbr2, result in abnormal vascular development especially of the yolk sac,
      leading to embryonic lethality. There are significant differences between murine
      and primate development that limit interpretation of studies from mouse models.
      Thus, to examine the role of TGFbeta in early human vascular development we used
      the model of differentiating human embryonic stem cell-derived embryoid bodies to
      recapitulate early stages of embryonic development. TGFbeta was applied for
      different time frames after initiation of embryoid body cultures to assess its
      effect on differentiation. TGFbeta inhibited the expression of endodermal,
      endothelial and hematopoietic markers, which contrasts with findings in the mouse
      in which TGFbeta reduced the level of endodermal markers but increased
      endothelial marker expression. The inhibition observed was not due to changes in
      proliferation or apoptosis. This marked contrast between the two species may
      reflect the different origins of the yolk sac hemangiogenic lineages in mouse and
      human. TGFbeta effects on the hypoblast, from which these cell lineages are
      derived in human, would decrease subsequent differentiation of hematopoietic,
      endothelial and endodermal cells. By contrast, TGFbeta action on murine
      hypoblast, while affecting endoderm would not affect the hemangiogenic lineages
      that are epiblast-derived in the mouse. This study highlights important
      differences between early human and mouse embryonic development and suggests a
      role of TGFbeta in human hypoblast differentiation.

PMID- 16449321
TI  - A signalling cascade involving PKC, Src and Cdc42 regulates podosome assembly in
      cultured endothelial cells in response to phorbol ester.
AB  - The involvement of Src, Cdc42, RhoA and PKC in the regulation of podosome
      assembly has been identified in various cell models. In endothelial cells, the
      ectopic expression of constitutively active mutants of Src or Cdc42, but not
      RhoA, induced the formation of podosomes. Short-term exposure to phorbol-12
      myristate-13-acetate (PMA) induced the appearance of podosomes and rosettes after
      initial disruption of stress fibres. Molecular analysis of PMA-induced podosomes
      and rosettes revealed that their composition was identical to that of podosomes
      described in other models. Pharmacological inhibition and siRNA knock-down
      experiments revealed that both PKCalpha and PKCdelta isotypes were necessary for
      podosome assembly. However, only constitutively active PKCalpha could mimic PMA
      in podosome formation. Src, Cdc42 and RhoA were required downstream of PKCs in
      this process. Src could be positioned between PKC and Cdc42 in a linear cascade
      leading to podosome assembly. Using in vitro matrix degradation assays, we
      demonstrated that PMA-induced podosomes are endowed with proteolytic activities
      involving MT1-MMP-mediated activation of MMP2. Endothelial podosomes may be
      involved in subendothelial matrix degradation during endothelium remodelling in
      pathophysiological processes.

PMID- 16449322
TI  - Androgens modulate the inflammatory response during acute wound healing.
AB  - Impaired wound healing states in the elderly lead to substantial morbidity and
      mortality, and a cost to the health services of over 9 billion dollars per annum.
      In addition to intrinsic ageing processes that per se cause delayed healing,
      studies have suggested marked differences in wound repair between the sexes. We
      have previously reported that, castration of male mice results in a striking
      acceleration of local cutaneous wound healing and dampens the associated
      inflammatory response. In this study, we report that systemic 5alpha-reductase
      inhibition, which blocks the conversion of testosterone to its more active
      metabolite 5alpha-dihydrotestosterone, mimics the effects of castration in a rat
      model of cutaneous wound healing. The mechanisms underlying the observed effects
      involve a direct, cell-specific upregulation of pro-inflammatory cytokine
      expression by macrophages, but not fibroblasts, in response to androgens.
      Androgens require the transforming growth factor beta signalling intermediate
      Smad3 to be present in order to influence repair and local pro-inflammatory
      cytokine levels. That reducing 5alpha-dihydrotestosterone levels through 5alpha
      reductase antagonism markedly accelerates healing suggests a specific target for
      future therapeutic intervention in impaired wound healing states in elderly
      males.

PMID- 16449323
TI  - Inhibition of TPO-induced MEK or mTOR activity induces opposite effects on the
      ploidy of human differentiating megakaryocytes.
AB  - The megakaryocyte is a paradigm for mammalian polyploid cells. However, the
      mechanisms underlying megakaryocytic polyploidization have not been elucidated.
      In this study, we investigated the role of Shc-Ras-MAPK and PI3K-AKT-mTOR
      pathways in promoting megakaryocytic differentiation, maturation and
      polyploidization. CD34+ cells, purified from human peripheral blood, were induced
      in serum-free liquid suspension culture supplemented with thrombopoietin (TPO) to
      differentiate into a virtually pure megakaryocytic progeny (97-99% CD61+/CD41+
      cells). The early and repeated addition to cell cultures of low concentrations of
      PD98059, an inhibitor of MEK1/2 activation, gave rise to a population of large
      megakaryocytes showing an increase in DNA content and polylobated nuclei (from
      45% to 70% in control and treated cultures, respectively). Conversely, treatment
      with the mTOR inhibitor rapamycin strongly inhibited cell polyploidization, as
      compared with control cultures. Western blot analysis of PD98059-treated
      progenitor cells compared with the control showed a downmodulation of phospho-ERK
      1 and phospho-ERK 2 and a minimal influence on p70S6K activation; by contrast,
      p70S6K activation was completely inhibited in rapamycin-treated cells.
      Interestingly, the cyclin D3 localization was nuclear in PD98059-induced
      polyploid megakaryocytes, whereas it was completely cytoplasmic in those treated
      with rapamycin. Altogether, our results are in line with a model in which binding
      of TPO to the TPO receptor (mpl) could activate the rapamycin-sensitive PI3K-AKT
      mTOR-p70S6K pathway and its downstream targets in promoting megakaryocytic cell
      polyploidization.

PMID- 16449324
TI  - Distinct domains of the spinal muscular atrophy protein SMN are required for
      targeting to Cajal bodies in mammalian cells.
AB  - Mutations of the survival motor neuron gene SMN1 cause the inherited disease
      spinal muscular atrophy (SMA). The ubiquitous SMN protein facilitates the
      biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs). The protein
      is detected in the cytoplasm, nucleoplasm and enriched with snRNPs in nuclear
      Cajal bodies. It is structurally divided into at least an amino-terminal region
      rich in basic amino acid residues, a central Tudor domain, a self-association
      tyrosine-glycine-box and an exon7-encoded C-terminus. To examine the domains
      required for the intranuclear localization of SMN, we have used fluorescently
      tagged protein mutants transiently overexpressed in mammalian cells. The basic
      amino acid residues direct nucleolar localization of SMN mutants. The Tudor
      domain promotes localization of proteins in the nucleus and it cooperates with
      the basic amino acid residues and the tyrosine-glycine-box for protein
      localization in Cajal bodies. Moreover, the most frequent disease-linked mutant
      SMNDeltaex7 reduces accumulation of snRNPs in Cajal bodies, suggesting that the C
      terminus of SMN participates in targeting to Cajal bodies. A reduced number of
      Cajal bodies in patient fibroblasts associates with the absence of snRNPs in
      Cajal bodies, revealing that intranuclear snRNA organization is modified in
      disease. These results indicate that direct and indirect mechanisms regulate
      localization of SMN in Cajal bodies.

PMID- 16449325
TI  - Failure of microtubule-mediated peroxisome division and trafficking in disorders
      with reduced peroxisome abundance.
AB  - In contrast to peroxisomes in normal cells, remnant peroxisomes in cultured skin
      fibroblasts from a subset of the clinically severe peroxisomal disorders that
      includes the biogenesis disorder Zellweger syndrome and the single-enzyme defect
      D-bifunctional protein (D-BP) deficiency, are enlarged and significantly less
      abundant. We tested whether these features could be related to the known role of
      microtubules in peroxisome trafficking in mammalian cells. We found that remnant
      peroxisomes in fibroblasts from patients with PEX1-null Zellweger syndrome or D
      BP deficiency exhibited clustering and loss of alignment along peripheral
      microtubules. Similar effects were observed for both cultured embryonic
      fibroblasts and brain neurons from a PEX13-null mouse with a Zellweger-syndrome
      like phenotype, and a less-pronounced effect was observed for fibroblasts from an
      infantile Refsum patient who was homozygous for a milder PEX1 mutation. By
      contrast, such changes were not seen for patients with peroxisomal disorders
      characterized by normal peroxisome abundance and size. Stable overexpression of
      PEX11beta to induce peroxisome proliferation largely re-established the alignment
      of peroxisomal structures along peripheral microtubules in both PEX1-null and D
      BP-deficient cells. In D-BP-deficient cells, peroxisome division was apparently
      driven to completion, as induced peroxisomal structures were similar to the
      spherical parental structures. By contrast, in PEX1-null cells the majority of
      induced peroxisomal structures were elongated and tubular. These structures were
      apparently blocked at the division step, despite having recruited DLP1, a protein
      necessary for peroxisome fission. These findings indicate that the increased
      size, reduced abundance, and disturbed cytoplasmic distribution of peroxisomal
      structures in PEX1-null and D-BP-deficient cells reflect defects at different
      stages in peroxisome proliferation and division, processes that require
      association of these structures with, and dispersal along, microtubules.

PMID- 16449326
TI  - Ca2+ oscillations induced by testosterone enhance neurite outgrowth.
AB  - Testosterone has short- and long-term roles in regulating neuronal function.
      Here, we show rapid intracellular androgen receptor-independent effects of
      testosterone on intracellular Ca2+ in neuroblastoma cells. We identified
      testosterone-induced Ca2+ signals that began primarily at the neurite tip,
      followed by propagation towards the nucleus, which was then repeated to create an
      oscillatory pattern. The initial transient depended upon production of inositol
      1,4,5-trisphosphate [Ins(1,4,5)P3], but subsequent transients required both
      extracellular Ca2+ influx and Ca2+ release from intracellular stores. Inhibition
      of pertussis toxin-sensitive G-protein receptors or the use of siRNA for the
      Ins(1,4,5)P3 receptor type 1 blocked the Ca2+ response, whereas inhibition or
      knock-down of the intracellular androgen receptor was without effect. Cytosolic
      and nuclear Ca2+ were buffered with parvalbumin engineered to be targeted to the
      cytosol or nucleus. Cytoplasmic parvalbumin blocked Ca2+ signaling in both
      compartments; nuclear parvalbumin blocked only nuclear signals. Expression of a
      mutant parvalbumin did not modify the testosterone-induced Ca2+ signal. Neurite
      outgrowth in neuroblastoma cells was enhanced by the addition of testosterone.
      This effect was inhibited when cytosolic Ca2+ was buffered and was attenuated
      when parvalbumin was targeted to the nucleus. Our results are consistent with a
      fast effect of testosterone, involving Ins(1,4,5)P3-mediated Ca2+ oscillations
      and support the notion that there is synergism in the pathways used for neuronal
      cell differentiation involving rapid non-genomic effects and the classical
      genomic actions of androgens.

PMID- 16449327
TI  - Abp1 regulates pseudopodium number in chemotaxing Dictyostelium cells.
AB  - When starved, Dictyostelium cells respond to extracellular signals, polarize, and
      move with strong persistence into aggregation centers. Actin and actin-associated
      proteins play key roles in regulating both the morphology and directed movements
      of cells during chemotactic aggregation. Recently, we identified an ortholog of
      Abp1 in Dictyostelium (Dabp1). The first actin binding protein identified in
      yeast, Abp1 functions in actin-based endocytosis in yeast and in receptor
      mediated endocytosis in mammalian cells. To explore the functions for Abp1 in
      Dictyostelium, we examined the phenotypes of cells that overexpressed the Dabp1
      protein and cells that eliminated Dabp1 expression. In these mutants, most actin
      based processes were intact. However, cell motility was altered during early
      development. During chemotactic streaming, more than 90% of wild-type cells had a
      single leading pseudopodium and a single uropodium, whereas more than 27% of
      Dabp1 null cells projected multiple pseuodpodia. Similarly, approximately 90% of
      cells that overexpressed Dabp1 projected multiple pseudopodia during chemotactic
      streaming, and displayed reduced rates of cell movement. Expression of the SH3
      domain of Dabp1 showed this domain to be an important determinant in regulating
      pseudopodium number. These results suggest that Abp1 controls pseudopodium number
      and motility in early stages of chemotactic aggregation in Dictyostelium.

PMID- 16449329
TI  - The influence of depression, body mass index, and smoking on serum inhibin B
      levels in late reproductive-aged women.
AB  - CONTEXT: Women experiencing depression have difficult psychosocial functioning,
      and recent data suggest an earlier onset of menopause. Understanding the
      biological mechanism for the impairment of reproductive function associated with
      depression is important. OBJECTIVE: The objective of the study was to determine
      whether a lifetime history of depression is associated with reduced ovarian
      reserve as reflected in serum levels of the granulosa cell product, inhibin B.
      DESIGN: Residual serum samples from a subset of patients in the Harvard Study of
      Cycles and Moods were collected. SETTING: Patients were recruited from seven
      Boston-area communities. PATIENTS: Women with or without a history of major
      depression, based on structured clinical interviews for Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition, were enrolled. A subset
      of patients who had provided an early follicular phase blood specimen at study
      enrollment and two or more other samples over the first 18-month period of follow
      up were included. INTERVENTION: There were no interventions. MAIN OUTCOME
      MEASURE: Serum inhibin B levels were measured. RESULTS: Serum FSH levels were
      higher in women with a history of depression, whereas inhibin B levels did not
      differ between groups. Body mass index and age were significantly and inversely
      related to serum inhibin B levels. Smoking history was noted, for the first time,
      to have a significant negative association with inhibin B levels. CONCLUSIONS:
      Smoking has a direct negative effect on ovarian reserve, as suggested by
      decreased serum inhibin B levels. In contrast, effects of depression on the
      reproductive axis may occur at the level of the pituitary and/or hypothalamus
      rather than at the gonadal level, as suggested by increased serum FSH levels.

PMID- 16449328
TI  - Dynamic expression and regulation of the corticotropin-releasing
      hormone/urocortin-receptor-binding protein system in the primate ovary during the
      menstrual cycle.
AB  - CONTEXT: Microarray analysis discovered that mRNA for CRH-binding protein (CRHBP)
      increased significantly in the primate corpus luteum (CL) after LH withdrawal.
      OBJECTIVE: Our objective was to determine whether other components of the
      CRH/urocortin-receptor-binding protein (UCN-R-BP) system are expressed in the CL
      during the menstrual cycle and regulated by LH. DESIGN: CL were collected from
      monkeys during the early (d 3-5 after the LH surge) to very late (d 18-19) luteal
      phase and from controls or animals receiving GnRH antagonist (Antide, 3 mg/kg
      body weight). CRH/UCN-R-BP system components were quantitated for mRNA levels by
      real-time PCR and analyzed for protein localization by immunohistochemistry.
      RESULTS: All genes encoding the CRH/UCN-R-BP system, except for UCN3, were
      expressed in the CL. CRH mRNA levels did not change during the luteal phase,
      whereas expression of UCN, UCN2, CRHR1, and CRHR2 was maximal at early or mid
      luteal phase before declining (P < 0.05) at the later stages. CRHBP mRNA levels
      were lowest at mid and increased (P < 0.05) in the late luteal phase. Suppressing
      gonadotropin secretion reduced UCN2 (P < 0.05) and increased CRHBP (P < 0.05)
      mRNA levels, without altering the expression of other ligands or receptors. CRH,
      UCN, UCN2 and their receptors were localized to the granulosa-lutein cells of the
      CL, whereas CRHBP was limited to the theca and theca-lutein cells of the
      preovulatory follicle and CL. CONCLUSIONS: A local CRH/UCN-R-BP system exists in
      the macaque CL that is dynamically expressed and LH regulated during the luteal
      phase of the menstrual cycle. Ligand-receptor activity may regulate luteal
      structure-function, at this point in an unknown manner, in primates.

PMID- 16449330
TI  - Identification of acromegalic patients at risk of developing colonic adenomas.
AB  - BACKGROUND: Acromegaly seems to be associated with an increased prevalence of
      colonic adenomas, although factors affecting their development and recurrence of
      the latter are not fully known. SUBJECTS AND METHODS: Seventy-nine patients with
      active acromegaly were prospectively followed up for 5 yr. Two hundred eighty
      healthy subjects served as controls. Colonoscopy and assessment of acromegaly
      activity were performed at 1-yr intervals. Acromegaly was defined as controlled
      if serum IGF-I levels were within the normal age-adjusted range. RESULTS: Colonic
      adenomas were found in 26 of 79 acromegalic patients (32.9%) and 60 of 280
      controls (21.4%) at baseline (P = 0.035, adjusted for age and sex, odds ratio
      1.82, 95% confidence interval, 1.02-3.25). Seven patients had hyperplastic
      polyps; the remaining 46 acromegalic patients had no detectable lesions at
      baseline and did not develop adenomas during the study period. Of the 26 patients
      with colonic adenomas at baseline, 16 (61.5%) had at least one recurrence of
      colonic adenomas (P < 0.0001 vs. patients without colonic lesions at baseline),
      and multiple recurrences were more frequent in patients with uncontrolled
      acromegaly (66.7% vs. 17.6% in patients with controlled acromegaly, P = 0.028).
      CONCLUSIONS: The first colonoscopy helps to identify acromegalic patients at high
      risk of developing colonic adenomas. If colonic adenomas are not present
      initially, it is unlikely that they develop thereafter, independently of
      metabolic control of acromegaly. Conversely, new lesions are frequent (and often
      multiple) in patients who already have colonic adenomas at baseline, particularly
      if acromegalic disease is poorly controlled by treatment.

PMID- 16449331
TI  - Bone turnover across the menopause transition: correlations with inhibins and
      follicle-stimulating hormone.
AB  - CONTEXT: Longitudinal clinical studies demonstrate that increases in bone
      turnover that occur in perimenopausal women correlate better with elevated serum
      FSH than with changes in serum estradiol (E2). This perimenopausal rise in FSH is
      due to a selective decrease in ovarian inhibin B (InhB). Our previous
      demonstration that inhibins suppress both osteoblast and osteoclast development
      suggests that changes in serum inhibins may regulate osteoblast and osteoclast
      differentiation and thereby bone turnover, independent of changes in sex
      steroids. OBJECTIVE: The objective of this study was to determine whether
      decreased serum inhibin A (InhA) and InhB levels correlate with increases in
      markers of bone turnover in women across the menopause transition and to evaluate
      serum inhibins as better predictors of bone turnover markers across the menopause
      transition than FSH or bioavailable E2. DESIGN: We studied a cross-sectional age
      stratified population sample of 188 pre- and postmenopausal women not using oral
      contraceptives or hormone replacement therapy (age, 21-85 yr). RESULTS: Serum
      InhA and InhB levels significantly correlated inversely with markers of bone
      formation and bone resorption in pre- and perimenopausal women and with markers
      of bone formation in postmenopausal women (InhA only). FSH was not significantly
      correlated with bone turnover in either pre- or postmenopausal women; however,
      FSH was significantly correlated with bone resorption (C-terminal collagen I
      cross-link) in perimenopausal women (age, 45-54 yr). Using multivariate analyses,
      serum InhA better predicted bone formation and resorption markers in
      premenopausal women than either FSH or bioavailable E2. CONCLUSIONS: Decreases in
      inhibin levels across the menopause transition are associated with increasing
      bone turnover, regardless of changes in sex steroids or FSH.

PMID- 16449332
TI  - Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine
      years) prospective study of its efficacy in the control of disease activity and
      tumor shrinkage.
AB  - CONTEXT: Neurosurgery is regarded as the first-line treatment of acromegaly.
      Because of its low cure rate in macro and invasive adenoma, the role of primary
      medical treatment is debated. OBJECTIVE: Our objective was to evaluate primary
      pharmacological treatment in acromegaly. DESIGN AND SETTING: We conducted an open
      prospective study at two Italian tertiary level centers. PATIENTS: We studied 67
      consecutive patients (36 women; age, 54.9 +/- 14.2 yr; 72% bearing macroadenoma).
      INTERVENTION: Individually tailored octreotide LAR (OCLAR) was administered. MAIN
      OUTCOME MEASURES: Outcomes included safe GH (<2.5 mug/liter), normal age-matched
      IGF-I levels, and tumor shrinkage. RESULTS: After a median follow-up of 48 months
      (range, 6-108 months), safe GH levels and normal age-matched IGF-I values were
      obtained by 68.7 and 70.1% of patients, respectively. Hormonal endpoints were
      achieved regardless of basal levels, and early results were predictive of
      outcome. Tumor shrank in 82.1% of patients by 62 +/- 31% (range, 0-100%),
      decreasing from 2101 +/- 2912 to 1010 +/- 2196 mm(3) (P < 0.0001). The higher the
      basal GH values and the greater the GH/IGF-I changes on treatment, the greater
      the tumor shrinkage. Tumor disappeared in three patients and was progressively
      reduced to empty sella in five patients; apparent magnetic resonance imaging
      cavernous sinus invasion disappeared in three. In males, testosterone increased,
      restoring eugonadism in 64% of hypogonadal patients. CONCLUSIONS: The efficacy on
      GH/IGF-I levels in unselected patients and the outstanding volumetric control
      indicate that treatment with OCLAR may be the first therapeutic approach to all
      acromegalic patients not amenable to surgical cure. Tumor shrinkage might also
      encourage the evaluation of primary OCLAR adoption in patients with initial
      visual field defects.

PMID- 16449333
TI  - Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and
      cortisol release in patients with anorexia nervosa.
AB  - CONTEXT: Anorexia nervosa (AN) is an eating disorder characterized by self
      induced starvation. Gastric hormone ghrelin, potent orexigen, and natural GH
      secretagogue are increased in AN. Although exogenous ghrelin stimulates appetite,
      GH, prolactin, and cortisol release in humans, its effects have not been studied,
      during infusions, in AN patients. OBJECTIVE: The objective of the study was to
      determine the effects of ghrelin on appetite, sleepiness, and neuroendocrine
      responses in AN patients. DESIGN: This was an acute interventional study.
      SETTING: The study was based at a hospital. Investigated SUBJECTS: Twenty-five
      young women, including nine patients diagnosed with AN with very low body weight,
      six AN patients who partially recovered their body weight but were still
      amenorrheic, and 10 constitutionally thin female subjects, without history of
      eating disorder, weight loss, with regular menstrual cycles, were included in the
      study. INTERVENTION: Each patient received 300-min iv infusion of ghrelin 5
      pmol/kg.min and was asked to complete Visual Analog Scale questionnaires hourly.
      MAIN OUTCOME MEASURES: Visual Analog Scale scores for appetite and sleepiness,
      GH, prolactin, and cortisol responses were measured. RESULTS: At baseline, AN
      patients had significantly higher ghrelin, GH, and cortisol levels and
      significantly lower leptin than constitutionally thin subjects. GH responses to
      ghrelin infusion were blunted in patients with AN. Ghrelin administration did not
      significantly affect appetite but tended to increase sleepiness in AN patients.
      CONCLUSIONS: Ghrelin is unlikely to be effective as a single appetite stimulatory
      treatment for patients with AN. Our results suggest that AN patients are less
      sensitive to ghrelin in terms of GH response and appetite than healthy controls.
      Ghrelin effects on sleep need further studies.

PMID- 16449335
TI  - Increased plasma visfatin concentrations in morbidly obese subjects are reduced
      after gastric banding.
AB  - CONTEXT: The insulin-mimetic adipocytokine visfatin has been linked to obesity.
      The influence of weight loss on plasma visfatin concentrations in obese subjects
      is unknown yet. OBJECTIVES: In this study we investigated whether plasma visfatin
      concentrations are altered by weight loss in patients with obesity. DESIGN AND
      PATIENTS: In a prospective study, fasting plasma visfatin, leptin, and
      adiponectin concentrations were measured before and 6 months after gastric
      banding in 31 morbidly obese patients aged 40 +/- 11 yr with a body mass index
      (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI
      less than 25 kg/m(2) served as controls. RESULTS: Visfatin plasma concentrations
      were markedly elevated in obese subjects (0.037 +/- 0.008 microg/ml), compared
      with controls (0.001 +/- 0.000 microg/ml, P < 0.001). Gastric banding reduced BMI
      to 40 +/- 5 kg/m(2), visfatin to 19.2 +/- 10.9 ng/ml, and leptin from 39.0 +/-
      12.4 to 29.7 +/- 10.0 ng/ml and increased adiponectin from 0.015 +/- 0.007 to
      0.017 +/- 0.007 microg/ml (all P < 0.05) after 6 months. Insulin sensitivity as
      estimated by the homeostasis model assessment insulin resistance index was
      unchanged from 5.8 +/- 3.1 to 4.6 +/- 1.9 (P = 0.13), but individual changes of
      insulin resistance and visfatin were significantly associated (P < 0.05, r = 
      0.43). CONCLUSIONS: Elevated plasma visfatin concentrations in morbidly obese
      subjects are reduced after weight loss. This may be related to changes in insulin
      resistance over time.

PMID- 16449334
TI  - Lower total fasting plasma adiponectin concentrations are associated with higher
      metabolic rates.
AB  - CONTEXT: The possible role of adiponectin, a protein uniquely produced by the
      adipose tissue and significantly reduced in obesity and other insulin-resistant
      states, in the regulation of energy expenditure (EE) is still poorly understood.
      OBJECTIVE: The objective of the study was to investigate the relationship between
      total fasting plasma adiponectin concentrations and the various components of EE
      measured in a metabolic chamber in Pima Indians and to test whether body fat
      distribution may have a role in this association. DESIGN: This was a cross
      sectional study. SETTING: The study was an inpatient clinical research unit.
      PARTICIPANTS: Sixty nondiabetic Pima Indians (45 males and 15 females), aged 18
      45 yr, spanning a wide range of adiposity (body mass index 19.6-46.2 kg/m(2))
      participated in the study. MAIN OUTCOME MEASURES: Total fasting plasma
      adiponectin concentrations, EE (24-h respiratory chamber), insulin sensitivity
      (euglycemic-hyperisulinemic clamp), body composition (dual-energy x-ray
      absorptiometry), and body fat distribution (waist to thigh ratio) were the main
      outcome measures. RESULTS: Total fasting plasma adiponectin concentrations are
      negatively associated with sleep EE adjusted for sex, age, fat-free mass, and fat
      mass. This correlation is still significant, although attenuated, after inclusion
      of insulin-stimulated glucose disposal among the regressors and further
      attenuated when adjusted also for waist to thigh ratio. CONCLUSIONS: The decrease
      in total fasting plasma adiponectin concentrations that accompanies fat
      accumulation may be a mechanism to prevent further weight gain by decreasing
      insulin sensitivity and increasing energy expenditure.

PMID- 16449336
TI  - Impaired cognitive function in women with congenital adrenal hyperplasia.
AB  - CONTEXT: Congenital adrenal hyperplasia (CAH) is a disorder with a wide spectrum
      of severity. OBJECTIVE: The objective of this study was to investigate cognitive
      function in CAH women. DESIGN: This was a case-control study. SETTING: This study
      was conducted at a tertiary center for pediatric endocrinology at the University
      Hospital of Copenhagen. PARTICIPANTS: Thirty-five Danish CAH women (age 17-51 yr)
      were included, and participation rate was 84%. Control women were recruited
      through the Danish Civil Registration System and matched on age and education.
      MAIN OUTCOME MEASURES: An abbreviated form of the Wechsler Adult Intelligence
      Scale was used, i.e. full-scale intelligence quotient (IQ; five of 11 subtests),
      which included three of six verbal IQ subtests and two of five performance IQ
      subtests. RESULTS: A significantly lower IQ was found in CAH patients compared
      with controls with respect to mean full-scale IQ (84.5 vs. 99.1; P < 0.001), mean
      verbal IQ (86.6 vs. 97.3; P < 0.001), and mean performance IQ (85.7 vs. 101.3; P
      < 0.001). The salt-wasting CAH group had lower IQ scores than the simple
      virilizing CAH group, which reached significance for mean total IQ (81.2 vs.
      92.8, P = 0.04) and mean verbal IQ (84.7 vs. 95.5, P = 0.05), and additionally,
      lower scores than the late-onset CAH group, which reached significance for
      performance IQ (mean 81.5 vs. 96.2, P = 0.02). CONCLUSIONS: Impaired cognitive
      function was observed in patients with CAH, especially in salt-wasting CAH. These
      intriguing findings may reflect adverse effects of hyponatremic episodes,
      suboptimal postnatal hormone replacement therapy or prenatal adrenal androgen
      excess, and the potential psychosocial consequences of the disorder.

PMID- 16449337
TI  - Functional characterization of the natural human glucocorticoid receptor (hGR)
      mutants hGRalphaR477H and hGRalphaG679S associated with generalized
      glucocorticoid resistance.
AB  - BACKGROUND: Glucocorticoid resistance is often a result of mutations in the human
      glucocorticoid receptor alpha (hGRalpha) gene, which impair one or more of
      hGRalpha's functions. We investigated the molecular mechanisms through which two
      previously described mutant receptors, hGRalphaR477H and hGRalphaG679S, with
      amino acid substitutions in the DNA- and ligand-binding domains, respectively,
      affect glucocorticoid signal transduction. METHODS AND RESULTS: In transient
      transfection assays, hGRalphaR477H displayed no transcriptional activity, whereas
      hGRalphaG679S showed a 55% reduction in its ability to stimulate the
      transcription of the glucocorticoid-responsive mouse mammary tumor virus promoter
      in response to dexamethasone compared with the wild-type hGRalpha. Neither
      hGRalphaR477H nor hGRalphaG679S exerted a dominant negative effect upon the wild
      type receptor. Dexamethasone binding assays showed that hGRalphaR477H preserved
      normal affinity for the ligand, whereas hGRalphaG679S displayed a 2-fold
      reduction compared with hGRalpha. Nuclear translocation studies confirmed
      predominantly cytoplasmic localization of the mutant receptors in the absence of
      ligand. Exposure to dexamethasone resulted in slower translocation of
      hGRalphaR477H (25 min) and hGRalphaG679S (30 min) into the nucleus than the wild
      type hGRalpha (12 min). In chromatin immunoprecipitation assays in cells stably
      transfected with the mouse mammary tumor virus promoter, hGRalphaR477H did not
      bind to glucocorticoid-response elements, whereas hGRalphaG679S preserved its
      ability to bind to glucocorticoid-response elements. Finally, in glutathione-S
      transferase pull-down assays, hGRalphaG679S interacted with the glucocorticoid
      receptor-interacting protein 1 coactivator in vitro only through its activation
      function (AF)-1, unlike the hGRalphaR477H and hGRalpha, which interacted with the
      glucocorticoid receptor-interacting protein 1 through both their AF-1 and AF-2.
      CONCLUSIONS: The natural mutants hGRalphaR477H and hGRalphaG679S cause
      generalized glucocorticoid resistance by affecting different functions of the
      glucocorticoid receptor, which span the cascade of the hGR signaling system.

PMID- 16449338
TI  - Cortistatin-17 and somatostatin-14 display the same effects on growth hormone,
      prolactin, and insulin secretion in patients with acromegaly or prolactinoma.
AB  - CONTEXT: Cortistatin binds all somatostatin receptor subtypes but also has
      particular central actions; moreover, a specific cortistatin receptor has also
      been discovered. OBJECTIVE: We compared the endocrine effects of cortistatin-17
      with those of somatostatin-14 in patients with acromegaly (ACRO) or prolactinoma
      (PRLOMA). Normal subjects (NS) were studied as control group. DESIGN: All
      subjects underwent the following tests: 1) saline, 2) somatostatin-14 (2.0
      microg/kg.h iv, 0-120 min) and 3) cortistatin-17 (2.0 microg/kg.h iv, 0-120 min)
      infusion. RESULTS: Cortistatin-17 and somatostatin-14 inhibited GH secretion to
      the same extent in ACRO (P < 0.05) and NS (P < 0.01). Cortistatin-17 and
      somatostatin-14 inhibited PRL secretion in PRLOMA (P < 0.05), to some extent in
      ACRO (P value not significant), but not in NS. Insulin secretion was inhibited by
      both cortistatin-17 and somatostatin-14 to the same extent in all groups (P <
      0.05). CONCLUSIONS: Cortistatin-17 and somatostatin-14 display the same effects
      on GH, PRL, and insulin secretion in patients with ACRO or PRLOMA.

PMID- 16449339
TI  - Short-term changes in bone turnover markers and bone mineral density response to
      parathyroid hormone in postmenopausal women with osteoporosis.
AB  - CONTEXT: Treatment of osteoporotic women with PTH increases biochemical markers
      of bone turnover, increases axial bone mineral density (BMD), and reduces
      fracture risk. OBJECTIVE: Our objective was to determine the relationship between
      levels of baseline turnover before PTH therapy and short-term changes in turnover
      during PTH therapy and subsequent changes in areal and volumetric BMD. DESIGN AND
      SETTING: We conducted a randomized, placebo-controlled trial at four academic
      centers. PATIENTS: Patients included 238 postmenopausal women with low hip or
      spine BMD. INTERVENTION: Subjects were randomized to sc PTH (1-84), 100 mug/d
      (119 women), for 1 yr. MAIN OUTCOME MEASURE: Bone turnover markers were measured
      in fasting blood samples collected before therapy and after 1 and 3 months. Areal
      and volumetric BMD at the spine and hip were assessed by dual-energy x-ray
      absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy.
      RESULTS: Among women treated with PTH alone, the relationships between baseline
      turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were
      inconsistent. Greater 1- and 3-month increases in turnover, particularly the
      formation marker N-propeptide of type I collagen, were associated with greater
      increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT,
      greater short-term increases in turnover were even more positively associated
      with 1-yr increases in BMD. Each sd increase in the 3-month change of N
      propeptide of type I collagen was associated with an a 21% greater increase in
      QCT spine trabecular BMD. CONCLUSIONS: Greater short-term changes in turnover
      with PTH therapy are associated with greater 1-yr increases in spine and hip BMD
      among postmenopausal osteoporotic women.

PMID- 16449340
TI  - Contributions of different fatty acid sources to very low-density lipoprotein
      triacylglycerol in the fasted and fed states.
AB  - CONTEXT: The liver's regulation of fatty acids (FAs) postprandially may
      contribute to risk of metabolic diseases. OBJECTIVE: Measurements of steady-state
      metabolism were used to investigate sources of FAs used for very low-density
      lipoprotein (VLDL)-triacylglycerol (TG) synthesis during fasting and feeding in
      vivo. DESIGN/INTERVENTION: Subjects were duodenally fed a formula labeled with
      the stable isotope glyceryl tri-palmitate-d(31) and iv infused with [1,2,3,4
      (13)C(4)]-palmitatic acid and [1-(13)C(1)]-acetate to quantitate the liver's use
      of FAs originating from adipose tissue and de novo lipogenesis.
      SETTING/PARTICIPANTS: This study of healthy men (n = 12; body mass index, 24.4 +/
      2.7 kg/m(2)) was conducted at a General Clinical Research Center. MAIN OUTCOME
      MEASURES: Concentrations of metabolites during fasting and feeding, sources of
      FAs used for lipoprotein synthesis, rate of appearance of serum nonesterified FA
      (NEFA), and VLDL-TG were measured. RESULTS: During fasting, 77.2 +/- 14.0% of
      VLDL-TG was derived from adipose FA recycling and 4.0 +/- 3.6% from lipogenesis;
      with feeding, 43.6 +/- 18.6% came from adipose FAs (P < 0.001), 8.2 +/- 5.1% from
      lipogenesis (P < 0.001), 15.2 +/- 13.7% from uptake of chylomicron-remnant TG,
      and 10.3 +/- 6.9% from dietary FA spillover into the serum NEFA pool. Fed-state
      VLDL-TG from NEFA reesterification decreased in proportion to the reduction in
      adipose NEFA appearance. CONCLUSION: These data: 1) quantify the extent to which
      the healthy liver manages its use of different sources of FAs that flow to it, 2)
      demonstrate how the postprandial reduction in adipose-NEFA flux may be partially
      replaced by other sources, and 3) highlight the potential for dietary FA
      spillover to support the continued dominance of NEFA as a substrate for VLDL-TG
      synthesis.

PMID- 16449341
TI  - Relationship of adolescent polycystic ovary syndrome to parental metabolic
      syndrome.
AB  - CONTEXT: We determined the relationship of metabolic syndrome (MBS) to polycystic
      ovary syndrome (PCOS). OBJECTIVE: We tested the hypothesis that parental MBS is
      related to the PCOS phenotype in their offspring. DESIGN/SETTING: We phenotyped
      for MBS and PCOS in our General Clinical Research Center. PATIENTS: Girls with
      PCOS, 12-19 yr old (n = 36, including one pair of siblings), and their parents
      (35 mothers, 19 fathers) were recruited from the Pediatric Endocrinology Clinic.
      Healthy girls, 12-19 yr old (n = 21), were recruited as a reference population.
      INTERVENTIONS: We measured anthropometrics, blood pressure, fasting lipids and
      androgens, oral glucose tolerance, and ultrasonographically determined polycystic
      ovary status. MAIN OUTCOME MEASURES: MBS in parents, and PCOS features in
      mothers, were related to the presence of PCOS features in probands. RESULTS:
      Fathers had strikingly high prevalence of excess adiposity (94% were obese or
      overweight) and MBS (79%). Premenopausal mothers more commonly had MBS (36%) than
      features of PCOS (< or =22%). Polycystic ovaries in proband offspring of
      premenopausal mothers were associated with maternal polycystic ovaries only in a
      minority of cases. Proband polycystic ovary status was completely concordant to
      fathers' MBS status (P = 0.008), but not their own or their mothers' MBS status,
      in families whose premenopausal mothers lacked polycystic ovaries. Proband
      prevalence of MBS was 27.8%, 3-fold greater than expected for obesity status.
      CONCLUSION: Familial factors related to paternal MBS seem to be fundamental to
      the pathogenesis of PCOS.

PMID- 16449342
TI  - Final height in girls with central idiopathic precocious puberty treated with
      gonadotropin-releasing hormone analog and oxandrolone.
AB  - CONTEXT: GnRH analogs (GnRHa) are considered the treatment of choice for central
      precocious puberty (CPP). During GnRHa administration, the suppression of the
      pituitary-gonadal axis results in decreased rates of linear growth and skeletal
      maturation and in improved adult height. However, in some patients, the growth
      deceleration is so marked that the expected improvement in predicted adult height
      is not achieved. OBJECTIVE: The objective of this study was to assess whether the
      addition of oxandrolone (Ox) may affect the height outcome of patients with CPP
      and growth deceleration during GnRHa treatment. DESIGN: This was an open-label,
      clinical study. SETTING: The study was performed at a pediatric endocrinology
      referral clinic. PATIENTS: Twenty patients with CPP and marked growth
      deceleration during GnRHa treatment were studied. INTERVENTIONS: Treatment
      consisted of GnRHa (Leuprorelina, 3.75 mg im every 28 d) alone (10 patients) or
      in combination with Ox (0.06 mg/kg.d by mouth) (10 patients). MAIN OUTCOME
      MEASURE: The main outcome measure was the patients' adult height. RESULTS: The
      adult height of the patients treated with GnRHa plus Ox was significantly higher
      than pretreatment predicted adult height (162.6 +/- 2.3 vs. 154.8 +/- 1.7 cm,
      mean +/- sem; P < 0.05) and target height (162.6 +/- 2.3 vs. 158.0 +/- 1.9; P >
      0.05). Patients treated with GnRHa alone reached an adult height similar to the
      pretreatment predicted adult height (151.9 +/- 1.2 vs. 155.4 +/- 2.1 cm) but
      significantly lower than target height (151.9 +/- 1.2 vs. 156.6 +/- 1.4 cm; P <
      0.005). No side effects were recorded in either group of patients. CONCLUSIONS:
      Combined GnRHa and Ox therapy is a viable treatment option for children with CPP
      and marked growth deceleration during treatment with GnRHa alone.

PMID- 16449343
TI  - Fat oxidation before and after a high fat load in the obese insulin-resistant
      state.
AB  - BACKGROUND: Obesity may be associated with a lowered use of fat as a fuel, which
      may contribute to the enlarged adipose tissue stores. AIM: The aim of the present
      study was to study fatty acid use in the fasting state and in response to a high
      fat load in a large cohort of obese subjects (n = 701) and a lean reference group
      (n = 113). METHODS: Subjects from eight European centers underwent a test meal
      challenge containing 95 en% fat [energy content 50% of estimated resting energy
      expenditure (EE)]. Fasting and postprandial fat oxidation and circulating
      metabolites and hormones were determined over a 3-h period. RESULTS: Postprandial
      fat oxidation (as percent of postprandial EE, adjusted for fat mass, age, gender,
      center, and energy content of the meal) decreased with increasing body mass index
      (BMI) category (P < 0.01), an effect present only in those obese subjects with a
      relatively low fasting fat oxidation (below median, interaction BMI category x
      fasting fat oxidation, P < 0.001). Fasting fat oxidation increased with
      increasing BMI category (P < 0.001), which was normalized after adjustment for
      fat-free mass and fat mass. Furthermore, insulin resistance was positively
      associated with postprandial fat oxidation (P < 0.05) and negatively associated
      with fasting fat oxidation (expressed as percent of EE), independent of body
      composition. CONCLUSIONS: The present data indicate an impaired capacity to
      regulate fat oxidation in the obese insulin-resistant state, which is
      hypothesized to play a role in the etiology of both obesity and insulin
      resistance.

PMID- 16449345
TI  - Evidence for a role of vasopressin in the control of aldosterone secretion in
      primary aldosteronism: in vitro and in vivo studies.
AB  - CONTEXT: Arginine vasopressin (AVP) stimulates steroid secretion from the normal
      human adrenal gland and some cortisol-producing adrenocortical tumors or
      hyperplasia through activation of the V(1a) receptor. OBJECTIVE: The objective of
      the study was to investigate in vitro and in vivo the possible involvement of AVP
      in the physiopathology of primary aldosteronism. DESIGN: The design of the study
      included immunohistochemical, pharmacological, and molecular studies on
      aldosterone-producing adenoma (APA), followed by a monocentric, crossover trial
      of the orally active V(1a) receptor antagonist, SR 49059, in a double blind,
      randomized, and placebo-controlled fashion. SETTING: The study was conducted at a
      university hospital and research laboratory. PATIENTS: The study population
      included eight untreated patients with primary aldosteronism, four with APA and
      four with idiopathic hyperaldosteronism. MAIN OUTCOME MEASURES: Aldosterone
      secretion of APA cells in vitro and plasma aldosterone, renin, and ACTH were
      measured. INTERVENTION: SR 49059 (200 mg once daily) or placebo was administered
      during two 1-wk treatment periods separated by a 2-wk washout. RESULTS: We
      observed the occurrence of AVP-containing cells in APA tissues. Administration of
      AVP to perifused APA cells induced an increase in aldosterone production, which
      was inhibited by a specific V(1a) antagonist. RT-PCR analysis showed the
      expression of V(1a) receptor mRNA in most APAs studied. In APA patients, SR 49059
      did not induce any effect on basal aldosterone secretion but provoked a plasma
      aldosterone response to orthostatism (P < 0.03) and strengthened the positive
      correlation between plasma aldosterone and ACTH. CONCLUSIONS: The present study
      indicates that functional V(1a) receptors are present in APA and suggests that
      AVP may exert an autocrine/paracrine control of aldosterone secretion in APA
      tissues.

PMID- 16449344
TI  - Sequential comparisons of one-month and three-month depot leuprolide regimens in
      central precocious puberty.
AB  - BACKGROUND: Dosing of monthly depot leuprolide (DL) in central precocious puberty
      (CPP) varies considerably. U.S. practitioners use 7.5-15 mg, in contrast with the
      international standard of 3.75 mg. Pubertal suppression using the newer 3-month
      DL also has been reported from Europe. To date there have been no direct
      comparisons of these different DL doses. OBJECTIVES: In an open 12-month
      protocol, we tested the efficacy of three DL doses (7.5 mg- and 3.75 mg-1 month
      and 11.25 mg-3 month) given sequentially to subjects treated for CPP. Primary
      outcome measures were stimulated gonadotropin (Gn) levels at 12-wk intervals. The
      null hypothesis was no difference among doses. METHODS: Both existing and new
      patients with CPP received our standard therapy (DL 7.5 mg every 4 wk) for a
      minimum of 24 wk. In subjects with DL-stimulated LH 2 IU/liter or less, the dose
      was changed to 3.75 mg every 4 wk and evaluated 12 wk later. Subjects who met LH
      criteria (<4.5 IU/liter) on 3.75 mg then received a single dose of 11.25 mg-3
      month and were reevaluated 12 wk later. Serum LH/FSH and sex steroids were
      obtained 40 min after DL injection. RESULTS: Thirty subjects were enrolled (20
      naive; 24 girls, 6 boys), and 21 were evaluated on all three DL doses. DL
      stimulated LH levels (mean +/- sd) were 1.30 +/- 0.74, 1.73 +/- 0.99, and 2.13 +/
      1.41 on 7.5 mg, 3.75 mg, and 11.25 mg-3 month, respectively (7.5 vs. 3.75 mg, P
      = 0.019; 7.5 mg vs. 11.25 mg-3 month, P = 0.004, Wilcoxon ranked sign test). Mean
      FSH levels were 2.86 +/- 1.91, 3.91 +/- 1.98, and 3.96 +/- 1.34, respectively
      (7.5 vs. 3.75 mg, P = 0.017; 7.5 mg vs. 11.25 mg-3 month, P = 0.020). No
      differences were detected in mean sex steroid levels. CONCLUSIONS: Stimulated LH
      and FSH levels were significantly higher during therapy with both the 3.75 mg and
      11.25 mg-3 month depot leuprolide doses, compared with 7.5 mg, contradicting the
      null hypothesis of no difference. These data suggest that low-dose 1- and 3-month
      DL preparations are associated with persistently greater gonadal stimulation in
      most CPP patients, but the LH/FSH results were not corroborated by differences in
      sex steroid levels. Whether various DL doses lead to long-term therapeutic
      differences remains to be determined.

PMID- 16449346
TI  - Dickkopf-1, an inhibitor of Wnt signaling, is regulated by progesterone in human
      endometrial stromal cells.
AB  - CONTEXT: Some members of the Wnt family, including ligands, receptors,
      inhibitors, and signaling components, are expressed in human endometrium.
      Dickkopf-1 (Dkk-1), a potent inhibitor of the Wnt signaling pathway, was recently
      found to be up-regulated in decidualizing endometrial stromal cells during the
      secretory phase of the menstrual cycle, suggesting regulation by progesterone.
      OBJECTIVES: To test the hypothesis that progesterone regulates Dkk-1 expression
      in human endometrial stromal cells, we investigated the following effects on
      stromal cell expression of Dkk-1 mRNA and protein: decidualizing stimuli
      (progesterone or cAMP), RU486 (an inhibitor of progesterone action), and
      withdrawal of progesterone. RESULTS: Short-term treatment (up to 72 h, which
      corresponds to the full decidualized phenotype in response to cAMP and an early
      response to progesterone) did not reveal regulation of Dkk-1 mRNA or protein by
      cAMP but did show induction of Dkk-1 expression when the cells were treated with
      progesterone, an effect that was blocked by RU486. In long-term cultures (from 14
      to 23 d, which corresponds to the full decidualized phenotype in response to
      progesterone), a significant increase in Dkk-1 mRNA and protein production was
      observed. Addition of RU486 or withdrawal of progesterone after long-term
      decidualization resulted in a decrease of Dkk-1 mRNA and protein to control
      levels. Estradiol alone had no effect on stromal Dkk-1 expression. CONCLUSIONS:
      These data strongly support regulation by progesterone of Dkk-1 mRNA synthesis
      and protein expression in human endometrial stromal cells and that the response
      is specific for progesterone and independent of cAMP and estradiol.

PMID- 16449347
TI  - Degree of facial and body terminal hair growth in unselected black and white
      women: toward a populational definition of hirsutism.
AB  - CONTEXT: Hirsutism (i.e. facial and body terminal hair growth in a male-like
      pattern in women) is the principal clinical sign of hyperandrogenism, although
      its definition remains unclear. OBJECTIVE: The purposes of the present study were
      to define 1) the degree of facial and body terminal hair, as assessed by the
      modified Ferriman-Gallwey (mFG) score, in unselected women from the general
      population; 2) the effect of race (Black and White) on the same; and 3) the
      normative cutoff values. DESIGN AND SETTING: We conducted a prospective
      observational study at a tertiary academic medical center. PATIENTS/PARTICIPANTS:
      Participants included 633 unselected White (n = 283) and Black (n = 350) women
      presenting for a preemployment physical exam. INTERVENTIONS: Interventions
      included history and physical examination. MAIN OUTCOME MEASURES: Terminal body
      hair growth was assessed using the mFG scoring system; nine body areas were
      scored from 0-4 for terminal hair growth distribution. RESULTS: The mFG scores
      were not normally distributed; although cluster analysis failed to identify a
      natural cutoff value or clustering of the population, principal component and
      univariate analyses denoted two nearly distinct clusters that occurred above and
      below an mFG value of 2, with the bulk of the scores below. Overall, an mFG score
      of at least 3 was observed in 22.1% of all subjects (i.e. the upper quartile); of
      these subjects, 69.3% complained of being hirsute, compared with 15.8% of women
      with an mFG score below this value, and similar to the proportion of women with
      an mFG score of at least 8 who considered themselves to be hirsute (70.0%).
      Overall, there were no significant differences between Black and White women.
      CONCLUSIONS: Our data indicate that the prevalence and degree of facial and body
      terminal hair growth, as assessed by the mFG score, is similar in Black and White
      women and that an mFG of at least 3 signals the population of women whose hair
      growth falls out of the norm.

PMID- 16449348
TI  - The Geodia cydonium galectin exhibits prototype and chimera-type characteristics
      and a unique sequence polymorphism within its carbohydrate recognition domain.
AB  - The ancestral galectin from the sponge Geodia cydonium (GCG) is classified on a
      structural basis to the prototype subfamily, whereas its carbohydrate-binding
      specificity is related to that of the mammalian chimera-type galectin-3. This
      dual coordination reveals GCG as a potential precursor of the later evolved
      galectin subfamilies, which is reflected in the primary structure of the protein.
      This study provides evidence that GCG is the LECT1 gene product, while neither a
      previously described LECT2 gene nor a functional LECT2 gene product was found in
      the specimen under investigation. The electrophoretically separated protein
      isomers with apparent molecular masses of 13, 15, and 16 kDa correspond to
      variants of the LECT1 protein-exhibiting peptide sequence polymorphisms that
      concern critical positions of the carbohydrate recognition domain (13 kDa: Leu51,
      Asn55, His130, Gly137; 15 kDa: Ser51, Asn55, Asn130, Gly137; 16 kDa: Ser51,
      Tyr55, Asn130, Glu137). Four residues, highly conserved in the galectin family,
      are substituted. None of the residues claimed to be involved in interactions with
      GalNAcalpha1-3 moieties at an extended binding subsite of galectin-3 was
      identified in the corresponding positions of GCG. Apparently, the substitutions
      do not confer distinct binding characteristics to the GCG variants as evidenced
      by binding studies with a recombinantly expressed 15-kDa isoform. The natural
      isoforms as well as the recombinant 15-kDa isoform oligomerize by the formation
      of non-covalent heteromeric or homomeric complexes. A phosphorylation of the
      galectin was confirmed neither by mass spectrometry nor by alkaline phosphatase
      treatment combined with isoelectric focusing.

PMID- 16449349
TI  - Enzymatic large-scale synthesis of MUC6-Tn glycoconjugates for antitumor
      vaccination.
AB  - In cancer, mucins are aberrantly O-glycosylated, and consequently, they express
      tumor-associated antigens such as the Tn determinant (alpha-GalNAc-O-Ser/Thr). As
      compared with normal tissues, they also exhibit a different pattern of
      expression. In particular, MUC6, which is normally expressed only in gastric
      tissues, has been detected in intestinal, pulmonary, colorectal, and breast
      carcinomas. Recently, we have shown that the MCF7 breast cancer cell line
      expresses MUC6-Tn glycoproteins in vivo. Cancer-associated mucins show antigenic
      differences from normal mucins, and as such, they may be used as potential
      targets for immunotherapy. To develop anticancer vaccines based on the Tn
      antigen, we prepared several MUC6-Tn glycoconjugates. To this end, we performed
      the GalNAc enzymatic transfer to two recombinant MUC6 proteins expressed in
      Escherichia coli, using UDP-N-acetylgalactosamine: polypeptide N
      acetylgalactosaminyltransferases (ppGalNAc-Ts), which catalyze in vivo the Tn
      antigen synthesis. We used either a mixture of ppGalNAc-Ts from MCF7 breast
      cancer cell extracts or a recombinant ppGalNAc-T1. In both cases, we achieved the
      synthesis of MUC6-Tn glycoconjugates at a semi-preparative scale (mg amounts).
      These glycoproteins displayed a high level of Tn antigens, although the overall
      density depends on both enzyme source and protein acceptor. These MUC6-Tn
      glycoconjugates were recognized by two anti-Tn monoclonal antibodies that are
      specific to human cancer cells. Moreover, the MUC6-Tn glycoconjugate glycosylated
      using MCF7 extracts as the ppGalNAc-T source was able to induce immunoglobulin G
      (IgG) antibodies that recognized a human tumor cell line. In conclusion, the
      large-scaled production of MUC6 with tumor-relevant glycoforms holds considerable
      promise for developing effective anticancer vaccines, and further studies of
      their immunological properties are warranted.

PMID- 16449350
TI  - Site-specific glycosylation analysis of the bovine lysosomal alpha-mannosidase.
AB  - Lysosomal alpha-mannosidase is a broad specificity exoglycosidase involved in the
      ordered degradation of glycoproteins. The bovine enzyme is used as an important
      model for understanding the inborn lysosomal storage disorder alpha-mannosidosis.
      This enzyme of about 1,000 amino acids consists of five peptide chains, namely a-
      to e-peptides and contains eight N-glycosylation sites. The N(497) glycosylation
      site of the c-peptide chain is evolutionary conserved among LAMANs and is very
      important for the maintenance of the lysosomal stability of the enzyme. In this
      work, relying on an approach based on mass spectrometric techniques in
      combination with exoglycosidase digestions and chemical derivatizations, we will
      report the detailed structures of the N-glycans and their distribution within six
      of the eight N-glycosylation sites of the bovine glycoprotein. The analysis of
      the PNGase F-released glycans from the bovine LAMAN revealed that the major
      structures fall into three classes, namely high-mannose-type (Fuc(0-1)Glc(0
      1)Man(4-9)GlcNAc(2)), hybrid-type (Gal(0-1)Man(4-5)GlcNAc(4)), and complex-type
      (Fuc(0-1)Gal(0-2)Man(3)GlcNAc(3-5)) N-glycans, with core fucosylation and
      bisecting GlcNAc. To investigate the exact structure of the N-glycans at each
      glycosylation site, the peptide chains of the bovine LAMAN were separated using
      SDS-PAGE and in-gel deglycosylation. These experiments revealed that the N(497)
      and N(930) sites, from the c- and e-peptides, contain only high-mannose-type
      glycans Glc(0-1)Man(5-9)GlcNAc(2), including the evolutionary conserved
      Glc(1)Man(9)GlcNAc(2) glycan, and Fuc(0-1)Man(3-5)GlcNAc(2), respectively.
      Therefore, to determine the microheterogeneity within the remaining glycosylation
      sites, the glycoprotein was reduced, carboxymethylated, and digested with
      trypsin. The tryptic fragments were then subjected to concanavalin A (Con A)
      affinity chromatography, and the material bound by Con A-Sepharose was purified
      using reverse-phase high-performance liquid chromatography (HPLC). The tandem
      mass spectrometry (ESI-MS/MS) and the MALDI analysis of the PNGase F-digested
      glycopeptides indicated that (1) N(692) and N(766) sites from the d-peptide chain
      both bear glycans consisting of high-mannose (Fuc(0-1)Man(3-7)GlcNAc(2)), hybrid
      (Fuc(0-1) Gal(0-1)Man(4-5)GlcNAc(4)), and complex (Fuc(0-1)Gal(0-2)Man(3)GlcNAc(4
      5)) structures; and (2) the N(367) site, from the b-peptide chain, is
      glycosylated only with high-mannose structures (Fuc(0-1)Man(3-5)GlcNAc(2)).
      Taking into consideration the data obtained from the analysis of either the in
      gel-released glycans from the abc- and c-peptides or the tryptic glycopeptide
      containing the N(367) site, the N(133) site, from the a-peptide, was shown to be
      glycosylated with truncated and high-mannose-type (Fuc(0-1)Man(4-5)GlcNAc(2)),
      complex-type (Fuc(0-1)Gal(0-1)Man(3)GlcNAc(5)), and hybrid-type (Fuc(0-1)Gal(0
      1)Man(5)GlcNAc(4)) glycans.

PMID- 16449351
TI  - Genetic restoration of aldose reductase to the collecting tubules restores
      maturation of the urine concentrating mechanism.
AB  - To investigate the underlying causes for aldose reductase deficiency-induced
      diabetes insipidus, we carried out studies with three genotypic groups of mice.
      These included wild-type mice, knockout mice, and a newly created bitransgenic
      line that was homozygous for both the aldose reductase null mutation and an
      aldose reductase knockin transgene driven by the kidney-specific cadherin
      promoter to direct transgene expression in the collecting tubule epithelial
      cells. We found that from early renal developmental stages onward, urine
      osmolality did not exceed 1,000 mosmol/kgH2O in aldose reductase-deficient mice.
      The functional defects were correlated with significant renal cellular and
      structural abnormalities that included cell shrinkage, apoptosis, disorganized
      tubular and vascular structures, and segmental atrophy. In contrast, the
      transgenic aldose reductase expression in the bitransgenic mice largely but
      incompletely rescued urine concentrating capacity and significantly improved
      renal cell survival, cellular morphology, and renal structures. Together, these
      results suggest that aldose reductase not only plays important roles in
      osmoregulation and medullary cell survival but may also be essential for the full
      maturation of the urine concentrating mechanism.

PMID- 16449352
TI  - Effect of simvastatin on high glucose- and angiotensin II-induced activation of
      the JAK/STAT pathway in mesangial cells.
AB  - In the current study, we investigated the effect of simvastatin on the ability of
      high glucose (HG) and ANG II to activate the JAK2-STAT signaling cascade and
      induce glomerular mesangial cell (GMC) growth. We found that pretreatment with
      simvastatin significantly inhibited HG- and ANG II-induced collagen IV
      production, JAK2 activation, and phosphorylation of STAT1 and STAT3 in GMC. We
      also found that the activation of JAK2 by HG and ANG II was dependent on the Rho
      family of GTPases. Consistent with these in vitro results, both albumin protein
      excretion and phosphorylation of JAK2, STAT1, and STAT3 were attenuated in renal
      glomeruli by administration of simvastatin in a streptozotocin-induced rat model
      of HG diabetes. This study demonstrates that simvastatin blocks ANG II-induced
      activation of the JAK/STAT pathway in the diabetic environment, in vitro and in
      vivo, and, thereby, provides new insights into the molecular mechanisms
      underlying early diabetic nephropathy.

PMID- 16449353
TI  - Furin cleavage activates the epithelial Na+ channel by relieving Na+ self
      inhibition.
AB  - Epithelial Na+ channels (ENaC) are inhibited by extracellular Na+, a process
      referred to as Na+ self-inhibition. We previously demonstrated that mutation of
      key residues within two furin cleavage consensus sites in alpha, or one site in
      gamma, blocked subunit proteolysis and inhibited channel activity when mutant
      channels were expressed in Xenopus laevis oocytes (Hughey RP, Bruns JB, Kinlough
      CL, Harkleroad KL, Tong Q, Carattino MD, Johnson JP, Stockand JD, and Kleyman TR.
      J Biol Chem 279: 18111-18114, 2004). Cleavage of subunits was also blocked by
      these mutations when expressed in Madin-Darby canine kidney cells, and both
      subunit cleavage and channel activity were blocked when wild-type subunits were
      expressed in furin-deficient Chinese hamster ovary cells. We now report that
      channels with mutant alpha-subunits lacking either one or both furin cleavage
      sites exhibited a marked enhancement of the Na+ self-inhibition response, while
      channels with a mutant gamma-subunit showed a modestly enhanced Na+ self
      inhibition response. Analysis of Na+ self-inhibition at varying [Na+] indicates
      that channels containing mutant alpha-subunits exhibit an increased Na+ affinity.
      At the single-channel level, channels with a mutant alpha-subunit had a low open
      probability (P(o)) in the presence of a high external [Na+] in the patch pipette.
      P(o) dramatically increased when trypsin was also present, or when a low external
      [Na+] was in the patch pipette. Our results suggest that furin cleavage of ENaC
      subunits activates the channels by relieving Na+ self-inhibition and that
      activation requires that the alpha-subunit be cleaved twice. Moreover, we
      demonstrate for the first time a clear relationship between ENaC P(o) and
      extracellular [Na+], supporting the notion that Na+ self-inhibition reflects a
      P(o) reduction due to high extracellular [Na+].

PMID- 16449354
TI  - Methyl-beta-cyclodextrin induces vasopressin-independent apical accumulation of
      aquaporin-2 in the isolated, perfused rat kidney.
AB  - Vasopressin increases urine concentration by stimulating plasma membrane
      accumulation of aquaporin-2 (AQP2) in collecting duct principal cells, allowing
      bulk water flow across the collecting duct from lumen to interstitium down an
      osmotic gradient. Mutations in the vasopressin type 2 receptor (V2R) cause
      hereditary X-linked nephrogenic diabetes insipidus (NDI), a disease characterized
      by excessive urination and dehydration. Recently, we showed that inhibition of
      endocytosis by the cholesterol-depleting drug methyl-beta-cyclodextrin (mbetaCD)
      induces plasma membrane accumulation of AQP2 in transfected renal epithelial
      cells overexpressing epitope-tagged AQP2. Here, we asked whether mbetaCD could
      induce membrane accumulation of AQP2 in situ using the isolated, perfused kidney
      (IPK). By immunofluorescence and electron microscopy, we show that AQP2 was
      shifted from a predominantly intracellular localization to the apical membrane of
      principal cells following 1-h perfusion of Sprague-Dawley rat kidneys with 5 mM
      mbetaCD. Quantification of staining revealed that the intensity of AQP2 was
      increased from 647+/-114 (control) to 1,968+/-299 units (mbetaCD; P<0.001), an
      effect similar to that seen after perfusion with 4 nM dDAVP (1,860+/-298,
      P<0.001). Similar changes were observed following mbetaCD perfusion of kidneys
      from vasopressin-deficient Brattleboro rats. No effect of mbetaCD treatment on
      the basolateral distribution of AQP3 and AQP4 was detected. These data indicate
      that AQP2 constitutively recycles between the apical membrane and intracellular
      vesicles in principal cells in situ and that inducing apical AQP2 accumulation by
      inhibiting AQP2 endocytosis is a feasible goal for bypassing the defective V2R
      signaling pathway in X-linked NDI.

PMID- 16449355
TI  - Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function
      in experimental cirrhosis.
AB  - Neutral endopeptidase degrades atrial natriuretic peptide (ANP) and bradykinin
      and may generate endothelin-1 from big-endothelin. In advanced cirrhosis, sodium
      retention is accompanied by elevated plasma ANP levels, and infusion of ANP
      causes hypotension, but in normal humans increasing the concentration of ANP
      through the inhibition of neutral endopeptidase, localized in renal proximal
      tubule cells, causes natriuresis without any arterial pressure drop. The purpose
      of this study was the assessment of kidney neutral endopeptidase expression and
      responses to candoxatrilat (a specific inhibitor of this enzyme) in rats with
      CCl4-induced cirrhosis. Two groups of control rats (n = 5) were injected with
      vehicle or 3 mg/kg candoxatrilat. Three groups of cirrhotic rats with ascites (n
      = 10) received vehicle alone or 3 or 10 mg/kg candoxatrilat. In cirrhotic rats,
      Western blot analysis revealed a 170% increase in renal neutral endopeptidase
      protein content (P < 0.03), mainly in the proximal nephron and macula densa, and
      both candoxatrilat dosages increased plasma ANP levels, urinary volume, and
      urinary excretion of sodium, ANP, and cGMP compared with vehicle alone (all P <
      0.03). Candoxatrilat (10 mg/kg) also reduced tubular solute-free water
      reabsorption (P < 0.03) in cirrhotic rats, but renal blood flow, arterial
      pressure, and plasma renin activity were unaffected. Neutral endopeptidase
      inhibition has natriuretic and aquaretic actions in cirrhosis without any effect
      on blood pressure and kidney perfusion due to a significant overexpression of
      this enzyme in renal cortex.

PMID- 16449356
TI  - Urea flux across MDCK-mUT-A2 monolayers is acutely sensitive to AVP, cAMP, and
      [Ca2+]i.
AB  - In this study, we engineered a Madin-Darby canine kidney (MDCK) type I cell line
      to stably express the mouse urea transporter UT-A2. Monolayers of MDCK-mUT-A2
      cells had a basal phloretin-inhibitable urea permeability of 8.4x10(-6)+/-0.3
      cm/s. Treatment of MDCK-mUT-A2 monolayers with AVP led to a rapid dose-dependent
      increase in trans-monolayer phloretin-inhibitable urea flux. The temporal pattern
      of response was markedly different from that observed for MDCK cells expressing
      rat UT-A1. Exposure of MDCK-mUT-A2 cells to either 10 microM forskolin or 250
      microM 8-bromo cAMP also increased urea flux rate. Inclusion of the PKA inhibitor
      H89 (10 microM) had no effect on the forskolin-stimulated increase in urea flux
      across MDCK-mUT-A2 monolayers. Treatment with either 10 microM CPA or 1 mM ATP
      also caused an increase in UT-A2-mediated urea flux, although these responses
      where transient compared with those induced by AVP or elevated cAMP. Taken
      together, these results show for the first time that UT-A2 is acutely sensitive
      to AVP, cAMP, or increased intracellular calcium.

PMID- 16449357
TI  - Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are
      independent of hyperaldosteronism in vasopressin escape.
AB  - Previously, we demonstrated that rats undergoing vasopressin escape had increased
      mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased
      renal protein abundance of the alpha-subunit of the epithelial sodium channel
      (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of
      gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J
      Physiol Renal Physiol 287: F1076-F1083, 2004; Ecelbarger CA, Knepper MA, and
      Verbalis JG. J Am Soc Nephrol 12: 207-217, 2001). Here, we determine whether
      changes in these renal proteins and MAP require elevated aldosterone levels. We
      performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats.
      Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP
      was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-D-arginine]
      vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion,
      seven rats in each group were offered a liquid diet [water load (WL)] or
      continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine
      aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed
      by early natriuresis followed by diuresis; however, urine volume and natriuresis
      were somewhat blunted. WL did not reduce the abundance or activity of 11-beta
      hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase
      in renal aldosterone-sensitive proteins and escape-associated increased MAP
      persisted in clamped rats. The densitometry of immunoblots for NCC, alpha- and
      gamma-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX
      SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids
      blunted the rise at least for NCC and gamma-ENaC (70 kDa). Overall, the increase
      in aldosterone observed in vasopressin escape is not necessary for the increased
      expression of NCC, alpha- or gamma-ENaC or increased MAP associated with
      "escape."

PMID- 16449358
TI  - Divalent metal transporter 1 in the kidney proximal tubule is expressed in late
      endosomes/lysosomal membranes: implications for renal handling of protein-metal
      complexes.
AB  - The H+-coupled polyligand transport protein divalent metal transporter 1 (DMT1)
      plays a key role in mammalian iron homeostasis. It has a widespread pattern of
      expression including tissues associated with iron acquisition and storage.
      Interestingly, it is also highly expressed in the kidney, yet its function in
      this tissue is unknown. The aim of this study was to determine the cellular
      location of DMT1 in proximal tubule cells as a first step to determining the role
      of this protein in the kidney. To do this we performed RT-PCR and immunostaining
      experiments using rat kidney and the S1 proximal tubule-derived WKPT-0293 Cl.2
      cell line. RT-PCR revealed that mRNAs encoding all four DMT1 splice variants were
      present in RNA extracted from rat kidney cortex or WKPT-0293 Cl.2 cells.
      Immunostaining of rat kidney cortex or WKPT-0293 Cl.2 cells showed that DMT1
      protein was expressed intracellularly and was not present in the plasma membrane.
      Expression of DMT1 partially colocalized with the late endosomal/lysosomal
      proteins LAMP1 and cathepsin-L. Using immunogold labeling, DMT1 was shown to be
      expressed in the membranes of late endosomes/lysosomes. Uptake of Alexa Fluor 546
      transferrin was only observed following application to the apical membrane of
      WKPT-0293 Cl.2 cells. Within these cells, Alexa Fluor 546-transferrin colocalized
      with DMT1. In conclusion, renal proximal tubular cells express DMT1 in the
      membranes of organelles, including late endosomes/lysosomes, associated with
      processing of apically sequestered transferrin. These findings have implications
      for renal iron handling and possibly for the handling of nephrotoxic metals that
      are also DMT1 ligands, including Cd2+.

PMID- 16449359
TI  - cGMP stimulates renin secretion in vivo by inhibiting phosphodiesterase-3.
AB  - The interaction between renin, nitric oxide (NO), and its second messenger cGMP
      is controversial. cAMP is the stimulatory second messenger for renin but is
      degraded by phosphodiesterases (PDEs). We previously reported that increasing
      endogenous cGMP in rats by inhibiting its breakdown by PDE-5 stimulated renin
      secretion rate (RSR). This could be reversed by selective inhibition of neuronal
      nitric oxide synthase (nNOS). PDE-3 metabolizes cAMP, but this can be inhibited
      by cGMP, suggesting that renal cGMP could stimulate RSR by diminishing PDE-3
      degradation of cAMP. Rats were anesthetized with Inactin before determination of
      blood pressure (BP), renal blood flow (RBF), and sampling of renal venous and
      arterial blood to determine RSR. In 13 rats, basal BP was 104 +/- 2 mmHg, RBF was
      6.1 ml x min(-1) x g kidney wt(-1) and RSR was 2.9 +/- 1.4 ng ANG I x h(-1) x
      min(-1). Inhibiting PDE-5 with 20 mg/kg body wt i.p. Zaprinast did not change
      hemodynamic parameters but increased RSR fivefold to 12.2 +/- 4.9 ng ANG I x h(
      1) x min(-1) (P < 0.05). Renal venous cAMP was increased by Zaprinast from 93.8
      +/- 27.9 to 149.2 +/- 36.0 pM x min(-1) x g kidney wt(-1) (P < 0.05). When
      another 10 rats were treated with the PDE-3 inhibitor Milrinone (0.4 microg/min
      over 30 min, which did not affect hemodynamics), RSR was elevated to 10.4 +/- 4.4
      ng ANG I x h(-1) x min(-1). Milrinone also increased renal venous cAMP from 212
      +/- 29 to 304 +/- 29 pM x min(-1) x g kidney wt(-1) (P < 0.025). Administration
      of Zaprinast to rats pretreated with Milrinone (n = 10) did not further increase
      in RSR (7.5 +/- 3.3 ng ANG I x h(-1) x min(-1)). These results are consistent
      with endogenous renal cGMP inhibiting PDE-3, which diminishes renal metabolism of
      cAMP. The resulting increase in cAMP serves as an endogenous stimulus for renin
      secretion. This suggests a pathway by which NO can indirectly stimulate RSR
      through its second messenger cGMP.

PMID- 16449360
TI  - Nutrition and reproduction in women.
AB  - Malnutrition is a major problem in developing countries, and obesity and eating
      disorders are increasingly common in developing as well as developed countries.
      The reproductive axis is closely linked to nutritional status, especially
      undernutrition in the female, and inhibitory pathways involving detectors in the
      hind brain suppress ovulation in subjects with weight loss. Recovery may occur
      after minimal reacquisition of weight because energy balance is more important
      than body fat mass. Anorexia nervosa and bulimia nervosa affect up to 5% of women
      of reproductive age causing amenorrhoea, infertility and, in those who do
      conceive, an increased likelihood of miscarriage. Obesity can affect reproduction
      through fat cell metabolism, steroids and secretion of proteins such as leptin
      and adiponectin and through changes induced at the level of important homeostatic
      factors such as pancreatic secretion of insulin, androgen synthesis by the ovary
      and sex hormone-binding globulin (SHBG) production by the liver. WHO estimates
      that 9 to 25% of women in developed countries are severely obese, and obese
      mothers are much more likely to have obese children, especially if they have
      gestational diabetes. Obesity-associated anovulation may lead to infertility and
      to a higher risk of miscarriage. Management of anovulation with obesity involves
      diet and exercise as well as standard approaches to ovulation induction. Many
      obese women conceive without assistance, but pregnancies in obese women have
      increased rates of pregnancy-associated hypertension, gestational diabetes, large
      babies, Cesarean section and perinatal mortality and morbidity. Among
      contraceptors, the fear of weight gain affects uptake and continuation of
      hormonal contraceptives, although existing trials indicate that any such effects
      are small. For all methods of hormonal contraception, weight above 70 kg is
      associated with increased failure rates.

PMID- 16449362
TI  - Association between PADI4 and rheumatoid arthritis: a meta-analysis.
AB  - OBJECTIVE: Polymorphisms and haplotypes of the peptidylarginine deiminase type 4
      gene (PADI4) have been reported to be associated with rheumatoid arthritis (RA)
      in a Japanese population. However, subsequent replication studies showed
      conflicting results. The aim of this study was to determine whether meta-analysis
      would prove the existence of the association. METHODS: PubMed was searched using
      the term 'PADI4' for articles from the publication of the first study to December
      2005. Replication studies that tested the association between PADI4 and RA were
      reviewed for meta-analysis. The Breslow-Day test for homogeneity across the
      studies was calculated. The Mantel-Haenszel procedure was used to pool odds
      ratios (OR) with 95% confidence intervals (CI) to evaluate the association.
      RESULTS: Six replication studies, one from Japan and five from Europe and North
      America, fulfilled the selection criteria for inclusion in the meta-analysis.
      Homogeneity was confirmed across the replication studies. The common OR was 1.14
      (95% CI = 1.07-1.21) for allelic distribution. The association was confirmed when
      only five replication studies in the European descent populations were combined
      (P = 0.0096, common OR = 1.10). CONCLUSIONS: Our meta-analysis showed a positive
      association between PADI4 and RA not only in the Japanese population but also in
      populations of European descent.

PMID- 16449361
TI  - Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan
      on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid
      synovial fibroblasts via down-regulation of NF-kappaB and p38.
AB  - OBJECTIVE: In rheumatoid arthritis (RA), it is well known that rheumatoid
      synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when
      stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta),
      which causes joint destruction. We have previously shown that hyaluronan (HA)
      inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However,
      CD44 mediates HA effects only partially, and intracellular events after the HA
      binding to its receptors remain unclear. We investigated the role of
      intercellular adhesion molecule-1 (ICAM-1), another cell surface receptor for HA,
      and the intracellular signalling pathways in the actions of HA. METHODS: RSF were
      isolated from rheumatoid synovial tissues by enzymatic digestion and cultured in
      monolayers. The confluent cells were incubated for 48 h with IL-1beta, IL-1beta
      in the presence of HA, or IL-1beta in the presence of HA with pretreatment with
      anti-ICAM-1 antibody. Secretion of MMP-1 and MMP-3 was analysed by immunoblotting
      and immunofluorescence cytochemistry. Immunofluorescence cytochemistry was also
      performed to evaluate binding of HA to ICAM-1. The phosphorylation of nuclear
      factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was analysed by
      immunoblotting. RESULTS: Production of MMP-1 and MMP-3 by RSF was stimulated by
      IL-1beta. HA at > or =2 mg/ml significantly inhibited MMP production induced by
      IL-1beta in a dose-dependent manner. Moreover, pretreatment with anti-ICAM-1
      antibody at 50 mug/ml significantly blocked the effects of HA on the actions of
      IL-1beta on RSF, as shown by immunoblotting and immunofluorescence cytochemistry.
      Another immunofluorescence cytochemistry study demonstrated that HA bound RSF via
      ICAM-1. Inhibition studies revealed the requirement of NF-kappaB, p38 and c-jun
      NH2-terminal kinase (JNK) for IL-1beta-induced MMP production. IL-1beta activated
      all three pathways, whereas HA down-regulated their phosphorylation. Pretreatment
      with anti-ICAM-1 antibody reversed the inhibitory effects of HA on the activation
      of NF-kappaB and p38 without affecting JNK. CONCLUSION: HA suppresses IL-1beta
      enhanced MMP-1 and MMP-3 synthesis in RSF via ICAM-1 through down-regulation of
      NF-kappaB and p38. Intra-articular injection of HA of high molecular weight may
      work through such a mechanism in RA joints.

PMID- 16449363
TI  - Fatigue in rheumatoid arthritis reflects pain, not disease activity.
AB  - OBJECTIVE: We determined the amount of fatigue experienced by patients with RA,
      and its relationship to synovitis, pain and other common clinical features. We
      also examined to what extent RA fatigue is improved by disease-modifying
      antirheumatic drugs (DMARDs) and anti-tumour necrosis factor (TNF) therapy.
      METHODS: We studied two cohorts of 238 and 274 RA patients cross-sectionally and
      examined treatment responses in 30 RA patients starting anti-TNF and 54 starting
      DMARDs followed for 3 and 6 months. We measured fatigue using visual analogue
      scores (VAS) and Medical Outcomes Study Short Form 36 (SF-36) vitality scores. We
      recorded the disease activity score for 28 joints and its components
      (tender/swollen joint counts, patient global assessment, ESR), morning stiffness,
      health assessment questionnaire, physician global assessment, erosive disease,
      nodules, rheumatoid factor, concomitant medications and illnesses, and the SF-36
      questionnaire. RESULTS: Fatigue was common in RA patients; over 80% had
      clinically relevant fatigue (VAS > or =20 mm), over 50% had high levels (VAS > or
      =50 mm). It was associated with pain and changes in mental health, particularly
      depression. In each of the two cross-sectional cohorts, this relationship was
      similar whichever measures of fatigue and mental health were used. Fatigue fell
      with DMARDs and anti-TNF: before treatment, 87% of patients had high fatigue,
      after treatment this fell to 50%. These treatment effects were mainly linked to
      improvements in pain. CONCLUSIONS: High fatigue levels characterize RA and are
      mainly linked to pain and depression. The association with disease activity is
      secondary. Fatigue falls with DMARD and anti-TNF therapy. The balance of evidence
      suggests that fatigue is centrally mediated in established RA.

PMID- 16449364
TI  - Association of a non-synonymous single-nucleotide polymorphism of DNASEI with SLE
      susceptibility.
AB  - OBJECTIVES: To investigate the association of a non-synonymous single-nucleotide
      polymorphism (SNP) in DNASEI with susceptibility to systemic lupus erythematosus
      (SLE) and the production of autoantibodies to nuclear antigens. METHODS: The
      Gln244Arg (rs1053874) SNP was studied in 276 SLE patients and in 368 healthy
      controls of Spanish ancestry. Its relationship with SLE susceptibility, serum
      DNase I activity, anti-ribonucleoprotein (RNP), anti-double-stranded DNA (dsDNA),
      anti-nucleosome and anti-single-stranded DNA (ssDNA) antibodies was determined.
      RESULTS: An association of the Gln244Arg SNP with SLE susceptibility that
      followed a recessive genetic model (P=0.002) was found. The GG genotype was more
      common in SLE patients (59.8%) than in controls (47.3%). However, the Gln244Arg
      genotype did not correlate with DNase I activity in sera from SLE patients or
      from controls. In addition, the Gln244Arg SNP did not influence autoantibody
      titres significantly. CONCLUSION: The association of the Gln244Arg SNP with SLE
      susceptibility indicates that common polymorphisms in DNASEI play a role in the
      genetics of SLE. However, the lack of effect of the Gln244Arg SNP on serum DNase
      I activity calls into question the direct involvement of this specific SNP.

PMID- 16449365
TI  - Spa therapy and balneotherapy for treating low back pain: meta-analysis of
      randomized trials.
AB  - OBJECTIVES: Low back pain is a major public health concern and complementary
      treatments are frequently used for this condition. The objective of this
      systematic review and meta-analysis was to assess the evidence for or against the
      effectiveness of spa therapy and balneotherapy for treating low back pain.
      METHODS: Systematic searches were conducted on Medline, Embase, Amed Cochrane
      Central, the UK National Research Register and ClincalTrials.gov (all until July
      2005). Hand searches were performed and experts contacted. Methodological quality
      was assessed using a standard scale. RESULTS: Five randomized clinical trials met
      all inclusion criteria. Quantitative data synthesis was performed. The data for
      spa therapy, assessed on a 100 mm visual analogue scale (VAS), suggest
      significant beneficial effects compared with waiting list control groups
      (weighted mean difference 26.6 mm, 95% confidence interval 20.4-32.8, n=442) for
      patients with chronic low back pain. For balneotherapy the data, assessed on a
      100 mm VAS, also suggest beneficial effects compared with control groups
      (weighted mean difference 18.8 mm, 95% confidence interval 10.3-27.3, n=138).
      CONCLUSIONS: Even though the data are scarce, there is encouraging evidence
      suggesting that spa therapy and balneotherapy may be effective for treating
      patients with low back pain. These data are not compelling but warrant rigorous
      large-scale trials.

PMID- 16449366
TI  - Two simple, reliable and valid tests of proximal muscle function, and their
      application to the management of idiopathic inflammatory myositis.
AB  - OBJECTIVE: To develop objective, isotonic, reliable and valid tests of upper (UL)
      and lower (LL) limb proximal muscle function for use in the management of
      idiopathic inflammatory myositis (IIM). METHODS: The '1 kg arm lift' test was
      devised to assess UL function and the '30 s chair stand' test was used for LL
      function. The tests were performed in 30 control subjects to determine short (24
      h) and long (2 week) interval test-retest reliability. Thirty-two patients with
      IIM were assessed over a period of 2 yr. RESULTS: In the control group both tests
      showed excellent test-retest reliability; Spearman correlation >0.8 for both
      tests over both time intervals. Twenty-four of the 32 IIM patients remained in
      remission over a mean period of 20.7 months throughout which scores varied by <5
      for the '1 kg arm lift' test and <3 for the '30 s chair stand' test from each
      patient's mean score. Eight patients relapsed with scores falling by >5 for the
      '1 kg arm lift' test and by >3 for the '30 s chair stand' test from the mean
      remission score in each case. Both UL and LL scores correlated inversely with
      serum creatinine kinase. CONCLUSION: Two isotonic tests of proximal muscle
      function are described. They exhibit excellent test-retest reliability and
      demonstrate construct validity in IIM. Both tests are responsive to changes in
      disease activity, offer physiological and practical advantages over existing
      tests of muscle function and are suitable for use in clinical practice.

PMID- 16449367
TI  - Serum levels of 8-isoprostane, a marker of oxidative stress, are elevated in
      patients with systemic sclerosis.
AB  - OBJECTIVE: To determine serum levels and clinical correlation of 8-isoprostane,
      which is produced in vivo through free radical-catalysed peroxidation of
      arachidonic acid and reflects oxidative stress, in patients with systemic
      sclerosis (SSc). METHODS: Serum 8-isoprostane levels from 32 patients with
      diffuse cutaneous SSc (dSSc) and 25 patients with limited cutaneous SSc (lSSc)
      were examined by enzyme-linked immunosorbent assay. RESULTS: Serum 8-isoprostane
      levels were elevated in dSSc and lSSc patients by 75-fold compared with normal
      controls (n=32). Serum 8-isoprostane levels correlated negatively with pulmonary
      function, such as percentage vital capacity and diffusion capacity for carbon
      monoxide, and correlated positively with renal vascular damage determined by
      colour flow Doppler ultrasonography. Serum 8-isoprostane levels also correlated
      positively with serum levels of IgG and anti-agalactosyl IgG autoantibody.
      CONCLUSION: Increased 8-isoprostane levels correlated with the severity of
      pulmonary fibrosis, the extent of renal vascular damage and immunological
      abnormalities in SSc, suggesting that enhanced oxidative stress is related to the
      development of SSc.

PMID- 16449368
TI  - Current provision of rheumatology education for undergraduate nursing,
      occupational therapy and physiotherapy students in the UK.
AB  - OBJECTIVES: Rheumatological conditions are common and all health professionals
      (HPs) therefore need sufficient knowledge and skills to manage patients safely
      and effectively. The aim of this study was to examine current undergraduate
      education in rheumatology for HPs in the UK. METHODS: A questionnaire was sent to
      curriculum organizers and clinical placement officers for all undergraduate
      courses in adult nursing, occupational therapy (OT) and physiotherapy (PT) in the
      UK to ascertain the nature and amount of rheumatology theory and clinical
      exposure provided. RESULTS: Of the 47 adult nursing, 26 OT and 30 PT
      undergraduate courses surveyed, 85-90% responded. Overall, rheumatology teaching
      is 5-10 h over 3 yr. Nursing students receive moderate/in-depth teaching on
      rheumatoid arthritis (RA) in only 52% of courses (OT 91%, PT 96%) and on
      osteoarthritis (OA) in 63% (OT 91%, PT 92%). Clinical experience of RA is
      probably/definitely available in only 56% of nursing courses (OT 72%, PT 88%),
      with similar results in OA. Overall, nursing students receive the least
      rheumatology exposure, particularly in psychosocial issues and symptom
      management, while PT students receive the most. OT students have limited
      opportunities for clinical exposure to psychosocial and joint protection issues.
      Use of local rheumatology clinical HP experts is variable (18-93%) and cross
      disciplinary exposure is limited (0-36%). Many educators consider their
      rheumatology training to be insufficient (nursing 50%, PT 42%, OT 24%).
      CONCLUSIONS: Rheumatology training for undergraduate HPs is limited in key areas
      and often fails to take advantage of local clinical expertise, with nursing
      students particularly restricted. Clinical HP experts should consider novel
      methods of addressing these shortfalls within the limited curriculum time
      available.

PMID- 16449369
TI  - Foot pain in community-dwelling older people: an evaluation of the Manchester
      Foot Pain and Disability Index.
AB  - OBJECTIVES: The objectives of this study were (i) to examine the psychometric
      properties of the Manchester Foot Pain and Disability Index (MFPDI) in community
      dwelling older people, and (ii) to determine the correlates of disabling foot
      pain in this age-group. METHODS: A questionnaire consisting of medical history,
      the MFPDI, the Goldberg Anxiety and Depression Scale (GADS) and the Medical
      Outcomes Study Short Form 36 (SF-36) was administered to a sample of 301
      community-dwelling people (117 men, 184 women) aged between 70 and 95 yr (mean
      77.2, s.d. 4.9), who also underwent a clinical assessment of foot problems.
      RESULTS: Using the MFPDI case definition, 108 people (36%) were found to have
      disabling foot pain. Within this subgroup, the MFPDI had high internal
      consistency (Cronbach's alpha=0.89). Principal components analysis revealed a
      four-factor structure representing the constructs of functional limitation, pain
      intensity, concern about appearance, and activity restriction, which explained
      62% of the variance in the original items. Participants with disabling foot pain
      were more likely to report pain in the back, hips, knees and hands or wrists, and
      exhibited flatter feet and less range of motion in the ankle joint. The MFPDI and
      its subscales were significantly associated with scores on the GADS depression
      subscale and the general health and mental health components of the SF-36.
      CONCLUSIONS: These findings confirm the high prevalence of disabling foot pain in
      older people, and suggest that the MFPDI is a suitable tool for assessing foot
      pain in this population.

PMID- 16449371
TI  - Too many decades or too little joined up thinking?

PMID- 16449370
TI  - Analgesic action of acetaminophen in symptomatic osteoarthritis of the knee.
AB  - OBJECTIVES: The study was designed to investigate the analgesic effects and
      mechanisms of acetaminophen (paracetamol) in symptomatic osteoarthritis (OA) of
      the knee. METHODS: Twenty patients with symptomatic OA were randomly allocated to
      two groups treated with either acetaminophen or rofecoxib for 3 months. Visits
      and measurements were scheduled upon entry (T0), at month 1 (T1) and at month 3
      (T3). The intensity of joint pain was evaluated with a 100-mm visual analogue
      scale (VAS). The physical function of the affected knee was evaluated with a
      questionnaire comparable to the Western Ontario McMaster Universities
      Osteoarthritis Index (WOMAC). Levels of serotonin, substance P (SP) and beta
      endorphin (BEND) were determined with commercial enzyme-linked immunoassay kits.
      The expression of kappa opioid receptor (KOR) in peripheral mononuclear blood
      cells (PBMCs) was quantified by real-time PCR. RESULTS: Both acetaminophen and
      rofecoxib relieved pain considerably but with different kinetics, and affected
      different biomarkers. Rofecoxib appeared to be more efficient, reducing pain
      intensity by 56% at T1 (P<0.01), whereas acetaminophen reduced it by only 29%.
      Physical function improved in both groups by T3. Correlated with the pain relief,
      acetaminophen significantly reduced plasma BEND levels, whereas rofecoxib did not
      do so. In both groups plasma SP levels were elevated compared with T0. A
      reduction in serum serotonin was detected in the rofecoxib group at T1 (P=0.004)
      but had recovered at T3. No changes in KOR mRNA in PBMCs were observed in either
      group. CONCLUSIONS: There is a correlation between reduction in circulating BEND
      and OA pain relief in patients treated with acetaminophen.

PMID- 16449372
TI  - Rheumatoid arthritis, pyrexia of unknown origin (PUO) and pancytopenia.

PMID- 16449373
TI  - High-affinity potassium and sodium transport systems in plants.
AB  - All living cells have an absolute requirement for K+, which must be taken up from
      the external medium. In contrast to marine organisms, which live in a medium with
      an inexhaustible supply of K+, terrestrial life evolved in oligotrophic
      environments where the low supply of K+ limited the growth of colonizing plants.
      In these limiting conditions Na+ could substitute for K+ in some cellular
      functions, but in others it is toxic. In the vacuole, Na+ is not toxic and can
      undertake osmotic functions, reducing the total K+ requirements and improving
      growth when the lack of K+ is a limiting factor. Because of these physiological
      requirements, the terrestrial life of plants depends on high-affinity K+ uptake
      systems and benefits from high-affinity Na+ uptake systems. In plants, both
      systems have received extensive attention during recent years and a clear insight
      of their functions is emerging. Some plant HAK transporters mediate high-affinity
      K+ uptake in yeast, mimicking K+ uptake in roots, while other members of the same
      family may be K+ transporters in the tonoplast. In parallel with the HAK
      transporters, some HKT transporters mediate high-affinity Na+ uptake without
      cotransporting K+. HKT transporters have two functions: (i) to take up Na+ from
      the soil solution to reduce K+ requirements when K+ is a limiting factor, and
      (ii) to reduce Na+ accumulation in leaves by both removing Na+ from the xylem sap
      and loading Na+ into the phloem sap.

PMID- 16449374
TI  - Phloem-sap feeding by animals: problems and solutions.
AB  - The incidence of phloem sap feeding by animals appears paradoxical. Although
      phloem sap is nutrient-rich compared with many other plant products and generally
      lacking in toxins and feeding deterrents, it is consumed as the dominant or sole
      diet by a very restricted range of animals, exclusively insects of the order
      Hemiptera. These insects display two sets of adaptations. First, linked to the
      high ratio of non-essential:essential amino acids in phloem sap, these insects
      contain symbiotic micro-organisms which provide them with essential amino acids.
      For example, bacteria of the genus Buchnera contribute up to 90% of the essential
      amino acids required by the pea aphid Acyrthosiphon pisum feeding on Vicia faba.
      Second, the insect tolerance of the very high sugar content and osmotic pressure
      of phloem sap is promoted by their possession in the gut of sucrase
      transglucosidase activity, which transforms excess ingested sugar into long-chain
      oligosaccharides voided via honeydew. Various other animals consume phloem sap by
      proxy, through feeding on the honeydew of phloem-feeding hemipterans. Honeydew is
      physiologically less extreme than phloem sap, with a higher essential:non
      essential amino acid ratio and lower osmotic pressure. Even so, ant species
      strongly dependent on honeydew as food may benefit from nutrients derived from
      their symbiotic bacteria Blochmannia.

PMID- 16449375
TI  - A proteomic approach to analysing responses of Arabidopsis thaliana callus cells
      to clinostat rotation.
AB  - Callus cells of Arabidopsis thaliana (cv. Landsberg erecta) were exposed for 8 h
      to a horizontal clinostat rotation (H, simulated weightlessness), a vertical
      clinostat rotation (V, clinostat control), or a stationary control (S) growth
      condition. The amount of glucose and fructose apparently decreased, while starch
      content increased in the H compared with the V- and S-treated cells. In order to
      investigate the influences of clinostat rotation on the cellular proteome
      further, the proteome alterations induced by horizontal and vertical clinostat
      rotation have been comparatively analysed by high-resolution two-dimensional (2
      D) gel electrophoresis and mass spectrometry. Image analysis of silver-stained 2
      D gels revealed that 80 protein spots showed quantitative and qualitative
      variations that were significantly (P <0.01) and reproducibly different between
      the clinorotated (H or V) and the stationary control samples. Protein spots
      excised from 2-D gels were analysed by microbe high performance liquid
      chromatography-ion trap-mass spectrometry (LC-IT-MS) to obtain the tandem mass
      (MS/MS) spectra. 18 protein spots, which showed significant expression alteration
      only under the H condition compared with those under V and S conditions, were
      identified. Of these proteins, seven were involved in stress responses, and four
      protein spots were identified as key enzymes in carbohydrate metabolism and lipid
      biosynthesis. Two reversibly glycosylated cell wall proteins were down-regulated
      in the H samples. Other proteins such as protein disulphide isomerase,
      transcription initiation factor IIF, and two ribosomal proteins also exhibited
      altered expression under the H condition. The data presented in this study
      illustrate that clinostat rotation of Arabidopsis callus cells has a significant
      impact on the expression of proteins involved in general stress responses,
      metabolic pathways, gene activation/transcription, protein synthesis, and cell
      wall biosynthesis.

PMID- 16449376
TI  - Cloning and functional analysis of a high DP fructan:fructan 1-fructosyl
      transferase from Echinops ritro (Asteraceae): comparison of the native and
      recombinant enzymes.
AB  - Inulin-type fructans are the simplest and most studied fructans and have become
      increasingly popular as prebiotic health-improving compounds. A natural variation
      in the degree of polymerization (DP) of inulins is observed within the family of
      the Asteraceae. Globe thistle (Echinops ritro), artichoke (Cynara scolymus), and
      Viguiera discolor biosynthesize fructans with a considerably higher DP than
      Cichorium intybus (chicory), Helianthus tuberosus (Jerusalem artichoke), and
      Dahlia variabilis. The higher DP in some species can be explained by the presence
      of special fructan:fructan 1-fructosyl transferases (high DP 1-FFTs), different
      from the classical low DP 1-FFTs. Here, the RT-PCR-based cloning of a high DP 1
      FFT cDNA from Echinops ritro is described, starting from peptide sequence
      information derived from the purified native high DP 1-FFT enzyme. The cDNA was
      successfully expressed in Pichia pastoris. A comparison is made between the mass
      fingerprints of the native, heterodimeric enzyme and its recombinant, monomeric
      counterpart (mass fingerprints and kinetical analysis) showing that they have
      very similar properties. The recombinant enzyme is a functional 1-FFT lacking
      invertase and 1-SST activities, but shows a small intrinsic 1-FEH activity. The
      enzyme is capable of producing a high DP inulin pattern in vitro, similar to the
      one observed in vivo. Depending on conditions, the enzyme is able to produce
      fructo-oligosaccharides (FOS) as well. Therefore, the enzyme might be suitable
      for both FOS and high DP inulin production in bioreactors. Alternatively,
      introduction of the high DP 1-FFT gene in chicory, a crop widely used for inulin
      extraction, could lead to an increase in DP which is useful for a number of
      specific industrial applications. 1-FFT expression analysis correlates well with
      high DP fructan accumulation in vivo, suggesting that the enzyme is responsible
      for high DP fructan formation in planta.

PMID- 16449378
TI  - Diel patterns of leaf C export and of main shoot growth for Flaveria linearis
      with altered leaf sucrose-starch partitioning.
AB  - Diel C export from source leaves of two Flaveria linearis lines [85-1: high
      cytosolic fructose-1,6-bisphosphatase (cytFBPase) and 84-9: low cytFBPase] were
      estimated using three methods, including leaf steady-state (14)CO(2) labelling,
      leaf metabolite analysis, and leaf dry mass analysis in conjunction with leaf
      CO(2) exchange measurements. Synthesis and accumulation of starch during the
      daytime were much higher in 84-9. Relative (14)C-export (export as a % of
      photosynthesis) in the light was 36% higher in 85-1. The diel export patterns
      from (14)C-analyses correlated with those based on metabolite or dry weight/gas
      exchange analyses during the daytime, but not during the night. Night-time export
      estimated from (14)C-disappearance was 3.6 times lower than those estimated using
      the other methods. Even though the starch degradation at night was greater for 84
      9, night-time export in 84-9 was similar to 85-1, since 84-9 showed both higher
      respiration and accumulation of soluble sugars (i.e. glucose) at night. Patterns
      of (14)C allocation to sink organs were also different in the two lines. Main
      stem growth was less in 84-9, being reduced most in the light when leaf export
      was lower relative to 85-1. Supplementation with sucrose for 1 h daily via the
      roots at a time when leaf export in 84-9 was low relative to 85-1 increased the
      stem growth rate of 84-9 to a level similar with that of 85-1. This study
      provides evidence that diel C availability predicted by source strength (e.g. C
      export rate) influences main stem extension growth and the pattern of sink
      development in F. linearis.

PMID- 16449377
TI  - Arabidopsis thaliana cyclic nucleotide gated channel 3 forms a non-selective ion
      transporter involved in germination and cation transport.
AB  - The Arabidopsis thaliana genome contains 20 cyclic nucleotide gated channel
      (CNGC) genes encoding putative non-selective ion channels. Classical and reverse
      genetic approaches have revealed that two members of this family (CNGC2 and
      CNGC4) play a role in plant defence responses whereas CNGC1 and CNGC10 may
      participate in heavy metal and cation transport. Yet, it remains to be resolved
      how the ion transport attributes of CNGCs are integrated into their physiological
      function. In this study, CNGC3 is characterized through heterologous expression,
      GUS- and GFP-reporter gene fusions, and by adopting a reverse genetics approach.
      A CNGC3-GFP fusion protein shows that it is mainly targeted to the plasma
      membrane. Promoter GUS studies demonstrate CNGC3 expression predominantly in the
      cortical and epidermal root cells, but also a ubiquitous presence in shoot
      tissues. Expression of CNGC3 in yeast indicates it can function as a Na(+) uptake
      and a K(+) uptake mechanism. cngc3 null mutations decreased seed germination in
      the presence of NaCl but not KCl. Relative to the wild type, mutant seedling
      growth is more resistant to the presence of toxic concentrations of NaCl and KCl.
      The ionic composition and ion uptake characteristics of wild-type and mutant
      seedlings suggests that the growth advantage in these conditions may be due to
      restricted ion influx in mutant plants, and that CNGC3 functions in the non
      selective uptake of monovalent cations in Arabidopsis root tissue.

PMID- 16449379
TI  - How periodic growth pattern and source/sink relations affect root growth in oak
      tree seedlings.
AB  - Seedlings of Quercus pubescens were grown in root boxes to study the growth
      pattern of the root system in relation to shoot development. Shoot growth was
      typically rhythmic. Root elongation was also periodic, in contrast to several
      previous reports on other Quercus species. Both taproot and lateral root
      elongation were depressed during expansion of the second leaf flush, with a more
      pronounced response of lateral root growth. Apical diameter of the taproot
      followed comparable but less prominent trends than taproot elongation. Modifying
      source/sink relationships through various defoliation treatments altered the root
      growth pattern. Ablation of source organs (mature leaves or cotyledons) amplified
      the decrease in root growth concomitant with leaf expansion. Root growth recovery
      was even more difficult when both cotyledons and mature leaves had been removed.
      Ablation of sink aerial organs (young leaves) initially suppressed competition
      for growth between the shoot and the root, and then caused a gradual decrease in
      lateral root growth. Antagonism between maximum leaf expansion and root growth
      reduction during the second flush, and various responses of seedlings with
      modified source/sink relationships, raise an hypothesis of mutual competition for
      carbohydrates. The gradual decrease in lateral root growth after ablation of
      young leaves suggests a long-term carbohydrate limitation, or auxin limitation as
      auxin sources have been removed.

PMID- 16449380
TI  - Metabolic regulation underlying tomato fruit development.
AB  - The development and maturation of tomato fruits has received considerable
      attention because of both the uniqueness of such processes to the biology of
      plants and the importance of these fruits as a component of the human diet.
      Molecular and genetic analysis of fruit development, and especially ripening of
      fleshy fruits, has resulted in significant gains in knowledge over recent years.
      A large amount of knowledge has been gathered on ethylene biosynthesis and
      response, cell wall metabolism, and environmental factors, such as light, that
      impact ripening. Considerably less attention has been paid directly to the
      general metabolic shifts that underpin these responses. Given the vast complexity
      of fruit metabolism, the focus chosen for this review is on primary metabolites
      and those secondary metabolites that are important with respect to fruit quality.
      Here, recent advances in dissecting tomato metabolic pathways are reviewed. Also
      discussed are recent examples in which the combined application of metabolic and
      transcriptional profiling, aimed at identifying candidate genes for modifying
      metabolite contents, was used.

PMID- 16449381
TI  - Arabidopsis variegation mutants: new insights into chloroplast biogenesis.
AB  - Plant variegations are characterized by the presence of white sectors in normally
      green tissues and organs. Whereas the white sectors contain defective plastids
      that lack coloured pigments, the green sectors contain morphologically normal
      chloroplasts. Variegation mutants are defective in chloroplast developmental
      processes and arise due to mutations in nuclear or organellar genes. Despite
      their widespread occurrence in nature, only a few variegations have been studied
      at the molecular level. In this review, recent progress toward understanding two
      Arabidopsis variegations, immutans (im) and var2 is summarized. Both im and var2
      are caused by nuclear recessive mutations and the responsible genes have been
      cloned and characterized. IMMUTANS functions as a chloroplast terminal oxidase
      that transfers electrons from the plastoquinol pool to oxygen. It appears to be a
      versatile electron sink, especially early in chloroplast development, when its
      function is crucial for carotenoid biosynthesis, and in excess light, when it
      serves as a 'safety valve'. IM also probably functions in chlororespiration. VAR2
      encodes a chloroplast FtsH metalloprotease (termed AtFtsH2). Along with other
      AtFtsH proteins (AtFtsH1, 5 and 8), it forms complexes in the thylakoid membrane
      that are probably involved in the process of PSII repair during photoinhibition.
      A model has been proposed to explain the mechanism of var2 variegation, which
      suggests that threshold levels of FtsH complexes are required for green sector
      formation. It is concluded that studies on im and var2 have provided novel
      insights into nuclear-chloroplast interactions and, especially, into mechanisms
      of photoprotection.

PMID- 16449382
TI  - High-throughput identification of IMCD proteins using LC-MS/MS.
AB  - The inner medullary collecting duct (IMCD) is an important site of vasopressin
      regulated water and urea transport. Here we have used protein mass spectrometry
      to investigate the proteome of the IMCD cell and how it is altered in response to
      long-term vasopressin administration in rats. IMCDs were isolated from inner
      medullas of rats, and IMCD proteins were identified by liquid
      chromatography/tandem mass spectrometry (LC-MS/MS). We present a WWW-based "IMCD
      Proteome Database" containing all IMCD proteins identified in this study (n =
      704) and prior MS-based identification studies (n = 301). We used the isotope
      coded affinity tag (ICAT) technique to identify IMCD proteins that change in
      abundance in response to vasopressin. Vasopressin analog (dDAVP) or vehicle was
      infused subcutaneously in Brattleboro rats for 3 days, and IMCDs were isolated
      for proteomic analysis. dDAVP and control samples were labeled with different
      cleavable ICAT reagents (mass difference 9 amu) and mixed. This was followed by
      one-dimensional SDS-PAGE separation, in-gel trypsin digestion, biotin-avidin
      affinity purification, and LC-MS/MS identification and quantification. Responses
      to vasopressin for a total of 165 proteins were quantified. Quantification, based
      on semiquantitative immunoblotting of 16 proteins for which antibodies were
      available, showed a high degree of correlation with ICAT results. In addition to
      aquaporin-2 and gamma-epithelial Na channel (gamma-ENaC), five of the
      immunoblotted proteins were substantially altered in abundance in response to
      dDAVP, viz., syntaxin-7, Rap1, GAPDH, heat shock protein (HSP)70, and cathepsin
      D. A 28-protein vasopressin signaling network was constructed using literature
      based network analysis software focusing on the newly identified proteins,
      providing several new hypotheses for future studies.

PMID- 16449383
TI  - Mapping cis-acting regulatory variation in recombinant congenic strains.
AB  - We present an integrated approach for the enriched detection of genes subject to
      cis-acting variation in the mouse genome. Gene expression profiling was performed
      with lung tissue from a panel of recombinant congenic strains (RCS) derived from
      A/J and C57BL/6J inbred mouse strains. A multiple-regression model measuring the
      association between gene expression level, donor strain of origin (DSO), and
      predominant strain background identified over 1,500 genes (P < 0.05) whose
      expression profiles differed according to the DSO. This model also identified
      over 1,200 genes whose expression showed dependence on background (P < 0.05),
      indicating the influence of background genetic context on transcription levels.
      Sequences obtained from 1-kb segments of 3'-untranslated regions identified
      single nucleotide polymorphisms in 64% of genes whose expression levels
      correlated with DSO status, compared with 29% of genes that displayed no
      association (P < 0.01, Fisher exact test). Allelic imbalance was identified in
      50% of genes positive for expression-DSO association, compared with 22% of
      negative genes (P < 0.05, Fisher exact test). Together, these results demonstrate
      the utility of RCS mice for identifying the roles of proximal genetic
      determinants and background genetic context in determining gene expression
      levels. We propose the use of this integrated experimental approach in multiple
      tissues from this and other RCS panels as a means for genome-wide cataloging of
      genetic regulatory mechanisms in laboratory strains of mice.

PMID- 16449384
TI  - trans-Stilbene oxide induces expression of genes involved in metabolism and
      transport in mouse liver via CAR and Nrf2 transcription factors.
AB  - trans-Stilbene oxide (TSO) induces drug metabolizing enzymes in rat and mouse
      liver. TSO is considered a phenobarbital-like compound because it induces Cyp2B
      mRNA expression in liver. Phenobarbital increases Cyp2B expression in liver via
      activation of the constitutive androstane receptor (CAR). The purpose of this
      study was to determine whether TSO induces gene expression in mouse liver via CAR
      activation. TSO increased CAR nuclear localization in mouse liver, activated the
      human Cyp2B6 promoter in liver in vivo, and activated a reporter plasmid that
      contains five nuclear receptor 1 (NR1) binding sites in HepG2 cells. TSO
      administration increased expression of Cyp2b10, NAD(P)H:quinone oxidoreductase
      (Nqo1), epoxide hydrolase, heme oxygenase-1, UDP-glucuronosyl-transferase (Ugt)
      1a6 and 2b5, and multidrug resistance-associated proteins (Mrp) 2 and 3 mRNA in
      livers from male mice. Cyp2b10 and epoxide hydrolase induction by TSO was
      decreased in livers from CAR-null mice, compared with wild-type mice, suggesting
      CAR involvement. In contrast, TSO administration induced Nqo1 and Mrp3 mRNA
      expression equally in livers from wild-type and CAR-null mice, suggesting that
      TSO induces expression of some genes through a mechanism independent of CAR. TSO
      increased nuclear staining of the transcription factor Nrf2 in liver, and
      activated an antioxidant/electrophile response element luciferase reporter
      construct that was transfected into HepG2 cells. In summary, in mice, TSO
      increases Cyp2b10 and epoxide hydrolase expression in mice via CAR, and
      potentially induces Nqo1 and Mrp3 expression via Nrf2. Moreover, our data
      demonstrate that a single compound can activate both CAR and Nrf2 transcription
      factors in liver.

PMID- 16449385
TI  - Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in
      familial Alzheimer's disease-linked presenilin-1 mutant neurons.
AB  - Presenilins (PS1/PS2) regulate proteolysis of beta-amyloid precursor protein
      (betaAPP) and affect its intracellular trafficking. Here, we demonstrate that a
      PS1-interacting protein, phospholipase D1 (PLD1), affects intracellular
      trafficking of betaAPP. Overexpression of PLD1 in PS1wt cells promotes generation
      of betaAPP-containing vesicles from the trans-Golgi network. Conversely,
      inhibition of PLD1 activity by 1-butanol decreases betaAPP trafficking in both wt
      and PS1-deficient cells. The subcellular localization of PLD1 is altered, and PLD
      enzymatic activity is reduced in cells expressing familial Alzheimer's disease
      (FAD) PS1 mutations compared with PS1wt cells. Overexpression of wt, but not
      catalytically inactive, PLD1 increases budding of betaAPP-containing vesicles
      from the trans-Golgi network in FAD mutant cells. Surface delivery of betaAPP is
      also increased by PLD1 in these cells. The impaired neurite outgrowth capacity in
      FAD mutant neurons was corrected by introducing PLD1 into these cells. The
      results indicate that PLD1 may represent a therapeutic target for rescuing
      compromised neuronal function in AD.

PMID- 16449386
TI  - Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid
      formation.
AB  - Presenilin (PS1/PS2) is a major component of gamma-secretase, the activity that
      mediates proteolysis of beta-amyloid precursor protein to generate beta-amyloid
      (Abeta). Here we demonstrate that PS1, through its loop region, binds to
      phospholipase D1 (PLD1), thereby recruiting it to the Golgi/trans-Golgi network.
      Overexpression of wild-type PLD1 reduces Abeta generation. Conversely, down
      regulation of endogenous PLD1 by small hairpin RNA elevates Abeta production. The
      Abeta-lowering effect of PLD1 is independent of its ability to promote vesicular
      budding of beta-amyloid precursor protein. The data indicate that overexpression
      of PLD1 decreases, and down-regulation of PLD1 increases, the catalytic activity,
      and the association of the subunits, of gamma-secretase.

PMID- 16449388
TI  - Multiple rare variants in NPC1L1 associated with reduced sterol absorption and
      plasma low-density lipoprotein levels.
AB  - An approach to understand quantitative traits was recently proposed based on the
      finding that nonsynonymous (NS) sequence variants in certain genes are
      preferentially enriched at one extreme of the population distribution. The NS
      variants, although individually rare, are cumulatively frequent and influence
      quantitative traits, such as plasma lipoprotein levels. Here, we use the NS
      variant technique to demonstrate that genetic variation in NPC1L1 contributes to
      variability in cholesterol absorption and plasma levels of low-density
      lipoproteins (LDLs). The ratio of plasma campesterol (a plant sterol) to
      lathosterol (a cholesterol precursor) was used to estimate relative cholesterol
      absorption in a population-based study. Nonsynonymous sequence variations in
      NPC1L1 were five times more common in low absorbers (n = 26 of 256) than in high
      absorbers (n = 5 of 256) (P < 0.001). The rare variants identified in low
      absorbers were found in 6% of 1,832 African-Americans and were associated with
      lower plasma levels of LDL cholesterol (LDL-C) (96 +/- 36 mg/dl vs. 105 +/- 36
      mg/dl; P = 0.005). These data, together with prior findings, reveal a genetic
      architecture for LDL-C levels that does not conform to current models for
      quantitative traits and indicate that a significant fraction of genetic variance
      in LDL-C is due to multiple alleles with modest effects that are present at low
      frequencies in the population.

PMID- 16449387
TI  - Lewy bodies.
AB  - Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of
      Parkinson's disease, but they occur in a number of neurodegenerative diseases and
      can be widespread in the nervous system. The characteristics, locations, and
      composition of LB are reviewed, with particular attention to alpha-synuclein
      (alpha-SYN), which appears to be the major component of LB. The propensity for
      alpha-SYN, a presynaptic protein widely expressed in the brain, to aggregate is
      because of an amyloidogenic central region. The factors that favor the
      aggregation of alpha-SYN and mechanisms of toxicity are examined, and a mechanism
      through which aggregates of alpha-SYN could induce mitochondrial dysfunction
      and/or release of proapoptotic molecules is proposed.

PMID- 16449389
TI  - Profile of Alan M. Lambowitz.

PMID- 16449390
TI  - Moving the frontiers forward: incorporating community-based participatory
      research into practice-based research networks.

PMID- 16449391
TI  - Community-based participatory research in practice-based research networks.
AB  - PURPOSE: We wanted to describe community-based participatory research in practice
      based research networks in the United States. METHODS: We surveyed all identified
      practice-based research networks (PBRNs) in the United States to find out whether
      they had a mechanism for obtaining feedback or involvement from the community of
      patients served by PBRN physicians. We asked open-ended questions on how they
      involve community members and whether they had plans for future involvement of
      community members and/or patients. RESULTS: We received 46 completed
      questionnaires (71% response rate). Twenty-four reported that they have some
      mechanism to involve community members and/or patients in their research. No PBRN
      reported full participatory methods; however, several PBRNs reported active
      involvement by community members to generate research ideas, review research
      protocols, interpret results, and disseminate findings. CONCLUSION: While perhaps
      not meeting the classical definition of CBPR, some PBRNs are involving community
      members and patients in their research. There is a wide spectrum of involvement
      by community members in PBRN research. Many PBRNs reported plans to involve
      community members in their research. We believe that community involvement will
      enhance PBRN research.

PMID- 16449392
TI  - Diabetes: how are we diagnosing and initially managing it?
AB  - PURPOSE: We undertook this study to examine the symptoms, clinical events, and
      types of health care encounters that preceded the diagnosis of diabetes mellitus
      in adults, and to examine changes in glycemic control and cardiovascular risk
      factors in the first year after a diabetes diagnosis. METHODS: We conducted a
      historical cohort study of patients in a large multispecialty medical group in
      Minnesota. Among 55,121 adults who were continuously enrolled in the health plan
      and receiving care at the study medical group from January 1, 1993, to December
      31, 1996, we identified 504 who received a new diagnosis of diabetes in 1995 or
      1996. Our main outcome measures were the type of symptoms at diagnosis; the
      clinical circumstances and type of encounter that led to diabetes diagnosis; and
      changes in glycemic control (assessed by hemoglobin A1c [HbA1c] value), low
      density lipoprotein cholesterol level, blood pressure (BP), aspirin use, and body
      weight in the first year after diagnosis, ascertained from a detailed review of
      medical records. RESULTS: Almost one third (32.3%) of adults with newly diagnosed
      diabetes had symptoms of hyperglycemia at initial diagnosis. Compared with
      patients who did not have hyperglycemia symptoms at diagnosis, those who did were
      younger and more often male, and had lower comorbidity scores and higher HbA1c
      values (9.9% vs 8.1%) at diagnosis (P <.01 for each comparison). In the 12 months
      after diagnosis, the group as a whole had significant improvements (P <.001) in
      HbA1c values (from 8.8% to 7.1%), systolic blood pressure (137.5 to 133.2 mm Hg),
      diastolic blood pressure (80.7 to 77.3 mm Hg), weight (207.7 to 201.1 lb), and
      aspirin use (15.3% to 26.1%). Improvements were seen in all patient subgroups,
      including those defined by symptoms at diagnosis and by visit type at diagnosis.
      CONCLUSIONS: Primary care practices may improve detection of undiagnosed diabetes
      in primary care and improve 1-year outcomes by being vigilant for symptoms of
      diabetes, by evaluating those at high risk for this disorder, and by instituting
      appropriate treatments at the time of diagnosis.

PMID- 16449393
TI  - Management of type 2 diabetes in the primary care setting: a practice-based
      research network study.
AB  - PURPOSE: We wanted to describe how primary care clinicians care for patients with
      type 2 diabetes. METHODS: We undertook a cross-sectional study of 95 primary care
      clinicians and 822 of their established patients with type 2 diabetes from 4
      practice-based, primary care research networks in the United States. Clinicians
      were surveyed about their training and practice. Patients completed a self
      administered questionnaire about their care, and medical records were reviewed
      for complications, treatment, and diabetes-control indicators. RESULTS:
      Participating clinicians (average age, 45.7 years) saw an average of 32.6 adult
      patients with diabetes per month. Patients (average age, 59.7 years) reported a
      mean duration of diabetes of 9.1 years, with 34.3% having had the disease more
      than 10 years. Nearly one half (47.5%) of the patients had at least 1 diabetes
      related complication, and 60.8% reported a body mass index greater than 30. Mean
      glycosylated hemoglobin (HbA1c) level was 7.6% (SD 1.73), and 40.5% of patients
      had values <7%. Only 35.3% of patients had adequate blood pressure control
      (<130/85 mm Hg), and only 43.7% had low-density lipoprotein cholesterol (LDL-C)
      levels <100 mg/dL. Only 7.0% of patients met all 3 control targets. Multilevel
      models showed that patient ethnicity, practice type, involvement of midlevel
      clinicians, and treatment were associated with HbA1c level; patient age,
      education level, and practice type were associated with blood pressure control;
      and patient ethnicity was associated with LDL-C control. CONCLUSIONS: Only modest
      numbers of patients achieve established targets of diabetes control.
      Reengineering primary care practice may be necessary to substantially improve
      care.

PMID- 16449394
TI  - Quality of preventive care for diabetes: effects of visit frequency and competing
      demands.
AB  - PURPOSE: We sought to determine the association between timely receipt of
      diabetes-related preventive services and the longitudinal pattern of outpatient
      service use as characterized by a novel taxonomy that prioritized visits based on
      the Oregon State Prioritized Health Services List. METHODS: We performed a cross
      sectional analysis of mail survey and automated health care data for a population
      based sample of patients with diabetes enrolled in a health maintenance
      organization in Washington State (N = 4,463). Outcomes included American Diabetes
      Association-recommended preventive services, including regular hemoglobin A1C
      (HbA1C) monitoring, retinal examination, and microalbuminuria screening. Patients
      with fewer than 8 visits during the 2-year study period were considered
      infrequent users, while patients with 8 or more visits were classified as lower
      priority users if most visits were for conditions of relatively low rank on the
      Oregon list and as higher-priority users otherwise. RESULTS: After adjustment for
      social, demographic, and clinical factors, and depression, infrequent users had
      significantly reduced odds of receiving at least 1 HbA1C test (odds ratio [OR] =
      0.35, 95% confidence interval [CI], 0.24-0.51), retinal examination (OR = 0.74,
      95% CI, 0.63-0.86), and microalbuminuria screening (OR = 0.75, 95% CI, 0.58-0.96)
      relative to higher-priority users during the previous year. Lower-priority users
      also had relatively reduced odds of receiving at least 1 HbA(1C) test (OR = 0.59,
      95% CI, 0.35-1.01), retinal examination (OR = 0.68, 95% CI, 0.56-0.84), and
      microalbuminuria screening (OR = 0.79, 95% CI, 0.57-1.09) despite attending a
      similar mean number of total visits as higher-priority users. CONCLUSIONS:
      Patients who attend relatively few outpatient visits or who attend more frequent
      visits for predominantly lower-priority conditions are more likely to receive
      substandard preventive care for diabetes.

PMID- 16449395
TI  - Encounters by patients with type 2 diabetes--complex and demanding: an
      observational study.
AB  - PURPOSE: We wanted to examine the relationships between quality of diabetes care
      delivered, the type and length of encounter, and time to the next follow-up
      encounter. METHODS: The content of the physician-patient encounter was directly
      observed in 20 primary care clinics for 211 patients with type 2 diabetes
      mellitus. The quality of diabetes care was measured as the percentage of the 5
      following services delivered during the encounter if they had not been offered in
      the previous year: foot examination, referral for an eye examination, a
      glycosylated hemoglobin (HbA1c) measurement, a lipid panel, and a urine
      microalbumin test. RESULTS: All indicated services were performed in 33% of
      encounters. Compared with encounters for an acute illness, patients visiting for
      chronic disease follow-up were 4.8 (95% CI, 1.95%-12.01%) times more likely to
      receive 100% of all indicated services. Length of encounter was associated with
      percentage of services delivered, but only during chronic disease follow-up
      encounters (P = .02). Encounters during which 100% of all indicated services were
      delivered had a mean length of 19.4 minutes. The time to the next scheduled
      encounter was shorter if fewer services were delivered during the observed
      encounter (P = .009). CONCLUSIONS: Competing demands during primary care
      encounters require patient and physician to prioritize services delivered and
      defer indicated services to subsequent visits. Current models of patient care in
      primary care settings are inadequate to address the multitude of tasks facing
      clinicians, especially among patients with complex chronic illnesses. Innovative
      approaches and new models are needed to improve the quality of diabetes care.

PMID- 16449396
TI  - Effects of enhanced depression treatment on diabetes self-care.
AB  - PURPOSE: Among patients with diabetes, major depression is associated with more
      diabetic complications, lower medication adherence, and poorer self-care of
      diabetes. We reported earlier that enhanced depression care reduces depression
      symptoms but not hemoglobin A1c level. This study examined effects of depression
      interventions on self-management among depressed diabetic patients. METHODS: A
      total of 329 patients in 9 primary care clinics were randomized to an evidence
      based collaborative depression treatment (pharmacotherapy, problem-solving
      treatment, or both in combination) or usual primary care (routine medical
      services). Outcome measures included the Summary of Diabetes Self-Care Activities
      (SDSCA), reported at baseline and 3, 6, and 12 months, and medication non
      adherence as assessed by automated pharmacy refill data of oral hypoglycemic
      agents, lipid-lowering agents, and angiotensin-converting enzyme inhibitors. We
      used mixed regression models adjusted for baseline differences to compare the
      intervention with usual care groups at follow-up assessments. RESULTS: During the
      12-month intervention period, enhanced depression care and outcomes were not
      associated with improved diabetes self-care behaviors (healthy nutrition,
      physical activity, or smoking cessation). Relative to the usual care group, the
      intervention group reported a small decrease in body mass index (mean difference
      = 0.70 kg/m2, 95% CI, 0.17 to 1.24 kg/m2) and a higher rate of nonadherence to
      oral hypoglycemic agents (mean difference = -6.3%, 95% CI, -11.91% to -0.71%).
      Adherence to lipid-lowering agents and to antihypertensive medicines was similar
      for the 2 groups. CONCLUSIONS: In general, diabetes self-management did not
      improve among the enhanced depression treatment group during a 12-month period,
      except for small between-group differences of limited clinical importance.
      Research needs to assess whether self-care interventions tailored for specific
      conditions, in addition to enhanced depression care, can achieve better diabetes
      and depression outcomes.

PMID- 16449397
TI  - Shared decision making and the experience of partnership in primary care.
AB  - PURPOSE: Communication has been researched either as a set of behaviors or as a
      facet of the patient-physician relationship, often leading to conflicting
      results. To determine the relationship between these perspectives, we examined
      shared decision making (SDM) and the subjective experience of partnership for
      patients and physicians in primary care. METHODS: From a convenience sample of
      experienced primary care physicians in 3 clinics, we recruited a stratified
      sample of 18 English- or Spanish-speaking patients. Direct observation of visits
      was followed by videotape-triggered stimulated recall sessions with patients and
      physicians. We coded decision moments for objective evidence of SDM, using a
      structured instrument. We classified patients' and physicians' subjective
      experience of partnership as positive or negative by a consensus analysis of
      stimulated recall sessions. We combined results from these 2 analyses to generate
      4 archetypes of engagements and used grounded theory to identify themes
      associated with each archetype. RESULTS: The 18 visits yielded 125 decisions, 62
      (50%) of which demonstrated SDM. Eighty-two decisions were discussed in
      stimulated recall and available for combined analysis, resulting in 4 archetypes
      of engagement in decision making: full engagement (SDM present, subjective
      experience positive)--22%; simulated engagement (SDM present, subjective
      experience negative)--38%; assumed engagement (SDM absent, subjective experience
      positive)--21%; and nonengagement (SDM absent, subjective experience negative)-
      19%. Thematic analysis revealed that both relationship factors (eg, trust, power)
      and communication behavior influenced subjective experience of partnership.
      CONCLUSIONS: Combining direct observation and assessment of the subjective
      experience of partnership suggests that communication behavior does not ensure an
      experience of collaboration, and a positive subjective experience of partnership
      does not reflect full communication. Attempts to enhance patient-physician
      partnership must attend to both effective communication style and affective
      relationship dynamics.

PMID- 16449398
TI  - State anger and the risk of injury: a case-control and case-crossover study.
AB  - PURPOSE: Previous studies have examined anger at a given moment (state anger) and
      proxies for injury, or anger as a trait and injuries per se. Findings have been
      inconsistent. We sought to define further the relationship between state anger
      and risk of injury. METHODS: We conducted a case-control and case-crossover study
      in all 3 emergency departments in 1 county in Missouri. Cases were patients
      seeking care for an acute injury. They were compared with 2 controls: the patient
      himself or herself 24 hours before, and an individual recruited by telephone from
      the community and matched for age-group, sex, and time. Self-reported anger was
      assessed with 3 Likert scale items. Anger just before the injury was compared in
      case-crossover analyses with the respondent's own level of anger 24 hours before,
      and in standard case-control analyses with community participants' level of anger
      at the same hour the same day of the week in a subsequent week. RESULTS: Of 2,517
      patients, 2,446 provided data on anger just before the injury, and 2,117 reported
      data for 24 hours before injury. Of 1,856 community individuals, 1,533 provided
      complete data. Anger was prevalent. Of injured patients, 9%, 7%, and 4% reported
      feeling "quite a bit" or "extremely" "irritable," "angry," and "hostile,"
      respectively, just before injury. Odds ratios for risk of injury were notably
      higher for greater degrees of anger; for example, for "angry," they were 1.8 (95%
      confidence interval, 1.1-2.7) for "quite a bit" and 7.2 (3.9-13) for "extremely."
      Odds ratios in women were substantially lower than those in men. Anger was not
      associated with fall and traffic injuries, but anger was strongly associated with
      intentional injuries inflicted by another person in both men and women.
      CONCLUSIONS: High levels of self-reported state anger increase the risk of
      injury, especially among men, and specifically the risk of intentional injury in
      both sexes.

PMID- 16449400
TI  - The dark bridal canopy.
AB  - Physician narratives in family medicine have the potential to convey the vibrant
      spirit of our field and provide meaningful insights into disease, illness,
      suffering, and the nature of healing. They may also complement empirical
      research, education, and practice through their integrative, expressive nature.
      This true story depicts a challenge faced by the author while serving as a family
      physician in a desolate, desert region in Israel's southern Aravah Valley (south
      of the Dead Sea), where he was privileged to practice for a decade. The episode,
      a fatal car crash in which a newlywed Druse woman (a member of a secretive sect)
      was killed, involved much more than just the terse details listed in the
      emergency log. An example of a family medicine physician-and-self drama, this
      piece takes the reader beyond the basic medical facts into the experience and
      sensations of the event. It also provides a stark contrast to the usual medical
      description and emphasizes the importance of stories as reflective opportunities
      for improving health care, sustaining ourselves as practitioners, and maintaining
      the vitality of our field.

PMID- 16449399
TI  - Effect of improved primary care access on quality of depression care.
AB  - PURPOSE: We wanted to determine whether a major improvement in access to primary
      care during 2000 was associated with changes in the quality of care for patients
      with depression. METHODS: Health plan administrative data were analyzed by
      multilevel regression to compare the quality of care received by patients with
      depression between 1999 and 2001, a time without major changes in depression care
      guidelines. Approximately 6,000 patients with depression who received all care in
      a large multispecialty medical group during any single year were subjects for
      this study. Thirteen different quality measures assessed process quality under
      the dimensions of effectiveness, timeliness, safety, and patient-centeredness.
      RESULTS: The largest change was a reduction in the proportion of depressed
      patients with no follow-up visit in primary care after starting a new
      antidepressant medication: from 33.0% before a change in access to care to 15.4%
      afterward, P =.001. During the same period, continuity of care in primary care
      improved (>50% of primary care visits to 1 doctor increased from 67.3% to 74.0%,
      P = or <.001), as did persistence of 6-month antidepressant medication (from
      46.2% to 50.8%, P = or <.001). Further analyses found that the latter change was
      primarily associated with the change in continuity of care. Measures of
      subspecialty mental health care worsened during this time. CONCLUSION: Marked
      improvement in access to primary care for 1 year was associated with some
      improvement in primary care for patients with depression, but the mechanism
      appeared to be improved continuity. Those planning to implement advanced access
      to care need to do so in such a way that continuity of care is enhanced rather
      than harmed by the change.

PMID- 16449401
TI  - Boy Scouts for Henry.
AB  - "Can we do anything for you?" The question was embarrassing. Henry had been poked
      and prodded and preserved far beyond his wishes. In a medical system that scorns
      comfort care, a resident physician is troubled by the case of an elderly man with
      poor quality of life. An awkward attempt at a Boy Scout service project
      emphasizes how poorly we comfort the terminally ill despite modern technology and
      interventionalism.

PMID- 16449402
TI  - Patients' health literacy skills: the missing demographic variable in primary
      care research.

PMID- 16449403
TI  - Focus on practice redesign, quality improvement.

PMID- 16449404
TI  - The family medicine road to the NIH roadmap.

PMID- 16449405
TI  - Increased serum levels of 8-hydroxy-2'-deoxyguanosine in clinical depression.
AB  - OBJECTIVE: We sought to understand the pathophysiological effects of depression
      by examining group differences in serum levels of 8-hydroxy-2'-deoxyguanosine (8
      OHdG), a biomarker of oxidative damage. METHODS: Our sample consisted of 169
      participants. Eight-four of these participants met diagnostic criteria for
      clinical depression. The 85 participants in our comparison group were matched on
      age, gender, and ethnicity to the depressed group. 8-OHdG was measured by enzyme
      linked immunosorbent assay. RESULTS: After adjusting for age, gender,
      race/ethnicity, years of education, daily smoking, average number of alcoholic
      drinks per week, average amount of physical activity per week, and body mass
      index, participants in the depressed group had significantly higher levels of
      oxidative DNA damage compared with participants in the control group. Pairwise
      comparisons showed that participants with major depression had significantly
      higher levels of 8-OHdG than control subjects and marginally higher levels of 8
      OHdG compared with those with minor depression. Furthermore, participants with
      recurrent episodes of depression had more oxidative damage than participants with
      single episodes, who in turn had more damage than healthy control subjects.
      Finally, participants with recurrent episodes of major depression had more DNA
      damage than other depressed participants, who in turn had more damage than
      healthy control subjects. CONCLUSIONS: Our findings suggest that increased
      oxidative damage may represent a common pathophysiological mechanism, whereby
      depressed individuals become vulnerable to comorbid medical illness.

PMID- 16449406
TI  - Psychophysiological mechanisms in panic disorder: a correlative analysis of
      noradrenaline spillover, neuronal noradrenaline reuptake, power spectral analysis
      of heart rate variability, and psychological variables.
AB  - BACKGROUND: The risk of adverse clinical cardiac events is increased in patients
      with panic disorder (PD). We evaluated possible mechanistic links between PD and
      heart disease. We estimated cardiac vagal activity from heart rate variability
      (HRV) measurements and quantified sympathetic nervous system (SNS) activity using
      plasma noradrenaline tracer kinetics methodology. METHODS: Thirty-nine people
      with PD and 39 age- and gender-matched healthy volunteers were studied. In 19
      participants with PD, both HRV and plasma noradrenaline kinetics were tested; in
      20 with PD and 20 healthy volunteers, HRV measurements only were made, whereas in
      19 healthy volunteers, noradrenaline kinetics only was tested. All panic disorder
      participants completed psychological measures of anxiety sensitivity and state
      and trait anxiety; healthy volunteers in whom HRV was measured also provided
      psychological measures. RESULTS: Sympathetic nervous tone in the heart, based on
      rates of cardiac noradrenaline spillover, was normal in PD. Noradrenaline and
      adrenaline plasma clearance and plasma tritiated noradrenaline and adrenaline
      extraction in transit through the heart, all dependent on the noradrenaline
      transporter (NET), were reduced in PD. Psychometric testing linked inhibition of
      anger to this deficit in NET functioning. Anxiety sensitivity was specifically
      associated with impaired cardiac NET. High- and low-frequency heart rate spectral
      power was unrelated to all plasma noradrenaline kinetics measurements.
      CONCLUSION: Defective neuronal reuptake of noradrenaline, by augmenting the
      sympathetic neural signal in the heart, might have a dual effect, sensitizing the
      heart such as to lead to symptom development (and thus perhaps causing panic
      disorder) and, second, potentially contributing to adverse cardiac events in
      established PD.

PMID- 16449407
TI  - Cognition and all-cause mortality across the entire adult age range: health and
      lifestyle survey.
AB  - OBJECTIVE: To investigate the association of reaction time and brief measures of
      memory and spatial ability with all-cause mortality. METHODS: Participants were
      from the UK Health and Lifestyle Survey (HALS), a national sample survey of
      adults in England, Scotland, and Wales. In 1984/1985, data on lifestyle factors,
      socioeconomic status, and health were collected for 9,003 people. Cognitive data
      were collected for 7,414 individuals. All-cause mortality was investigated over
      19 years of follow-up in relation to simple and choice reaction time, performance
      on a short-term verbal declarative memory test, and on a test of visual-spatial
      reasoning. RESULTS: Slower and more variable simple and choice reaction times
      were significantly related to increased risk of all-cause mortality over 19 years
      of follow-up. The increased risk of all-cause mortality was partly attenuated
      after adjustments for socioeconomic status, health behaviors, and health status.
      A novel finding was the existence of an effect of reaction time on all-cause
      mortality in young adults. Poorer verbal memory ability was also significantly
      related to an increased risk of dying in young adults independently of reaction
      time score. CONCLUSION: Slower and more variable reaction time was related to
      higher mortality risk in younger as well as older participants. Among younger
      adults, higher memory ability was also associated with lower risk of dying. The
      cognition-mortality relationship may be explained in part by the brain's
      efficiency of information processing and memory performance.

PMID- 16449408
TI  - Do depression and anxiety mediate the link between educational attainment and
      CHD?
AB  - OBJECTIVE: Depression and anxiety are frequently hypothesized yet rarely examined
      pathways linking low socioeconomic status (SES) to coronary heart disease (CHD).
      This study evaluates depression and anxiety as mediators of the association
      between educational attainment and incident CHD. METHODS: Subjects (n = 6265, age
      25-74) were participants in NHANES I and follow-up studies, a longitudinal,
      nationally representative study of the US population. Measures of educational
      attainment and depressive and anxious symptoms (General Well-Being Schedule) were
      derived from the baseline interview and incident CHD from hospital records and
      death certificates. Analyses included logistic regression and Cox proportional
      hazards models. RESULTS: In fully adjusted models, less than high school
      (relative risk [RR] = 1.46; 95% confidence interval [CI], 1.15-1.86) and some
      college (RR = 1.40; 95% CI, 1.05-1.88) education were associated with increased
      CHD risk relative to a college education. High depressive (RR = 1.31; 95% CI,
      1.06-1.61) or anxious (RR = 1.35; 95% CI, 1.13-1.62) symptoms were associated
      with significantly increased CHD risk relative to low symptoms. Low educational
      levels were associated with increased risk for high depressive (OR = 3.43; 95%
      CI, 2.34-5.03) and anxious (OR = 1.71; 95% CI, 1.32-2.22) symptoms. However,
      depressive and anxious symptoms accounted for little of the association between
      education and CHD. CONCLUSION: Education and depressive and anxious symptoms are
      associated with each other and risk of incident CHD. Although depressive and
      anxious symptoms are highest among those with lowest levels of education, they do
      not appear to mediate the relation between educational attainment and incident
      CHD. Findings suggest the importance of interventions to reduce socioeconomic
      disadvantage and negative affect in preventing CHD.

PMID- 16449409
TI  - Heart rate responsivity to script-driven imagery in posttraumatic stress
      disorder: specificity of response and effects of psychotherapy.
AB  - OBJECTIVE: Previous psychophysiological studies of posttraumatic stress disorder
      (PTSD) have found heightened physiological responsivity to trauma-specific
      stimuli, but mostly in combat veterans with high comorbidity rates and with
      psychiatric medication. Our aim was to investigate psychophysiological responses
      in two new populations while excluding those confounding influences and to assess
      the effects of psychotherapy on such responses. METHODS: Thirty-nine subjects
      with PTSD (24 civilian outpatients and 15 police officers) and 15 trauma-exposed,
      non-PTSD control subjects underwent psychophysiological assessment while
      listening to neutral, stressful, and trauma scripts. Psychophysiological measures
      were heart rate (HR) and blood pressure in combination with subjective anxiety
      ratings. In a randomized clinical trial, 20 of the civilians were then assigned
      to treatment or waitlist groups. Psychophysiological assessment was repeated on
      them after the treatment stage. RESULTS: Both civilians and police with PTSD
      showed significantly higher HR responses to trauma scripts than the control
      subjects. After successful psychotherapy with the civilians, HR responsivity to
      the trauma scripts was significantly reduced, and it correlated positively with
      PTSD clinical symptoms. CONCLUSIONS: We confirmed previous findings of heightened
      psychophysiological responses in PTSD for two new populations while minimizing
      comorbidity and medication as confounding factors. Successful psychotherapy
      normalized HR response to trauma imagery.

PMID- 16449411
TI  - Depression and prehospital delay in the context of myocardial infarction.
AB  - OBJECTIVE: The purpose of this study was to evaluate how depression might
      influence treatment-seeking behaviors in the context of evolving symptoms of
      myocardial infarction (MI). METHODS: Post-MI patients (n = 433) completed a
      retrospective self-report measure of depressive symptoms with regard to the 2
      weeks preceding the MI and a semistructured interview regarding their treatment
      seeking behaviors. RESULTS: Survival analyses found that delay in seeking
      treatment for acute MI symptoms was observed among participants who (1)
      attributed their symptoms to noncardiac causes, (2) perceived their symptoms to
      be relatively mild, (3) experienced gastrointestinal distress, (4) did not
      experience sweating, and (5) reported being depressed during the 2 weeks before
      hospitalization. Subsidiary analyses indicated that, among depressive symptoms,
      sleep disturbance and fatigue predicted delay. CONCLUSION: Depression warrants
      further attention as a variable that may influence treatment seeking for MI
      symptoms. Results highlight the need to adequately screen for and treat
      depression among persons at risk for MI.

PMID- 16449410
TI  - Socioeconomic status, race, and diurnal cortisol decline in the Coronary Artery
      Risk Development in Young Adults (CARDIA) Study.
AB  - OBJECTIVES: The objectives of this study were to assess whether socioeconomic
      status (SES) is associated with dysregulation of the cortisol diurnal rhythm and
      whether this association is independent of race and occurs equally in whites and
      blacks; and to determine if an association between SES and cortisol can be
      explained (is mediated) by behavioral, social, and emotional differences across
      the SES gradient. METHODS: Seven hundred eighty-one subjects from a multisite
      sample representing both whites and blacks provided six saliva cortisol samples
      over the course of the day: at awakening, 45 minutes, 2.5 hours, 8 hours, and 12
      hours after awakening, and at bedtime. RESULTS: Both lower SES (education and
      income) and being black were associated with higher evening levels of cortisol.
      These relationships were independent of one another and SES associations with
      cortisol were similar across racial categories. The evidence was consistent with
      poorer health practices (primarily smoking), higher levels of depressive
      symptoms, poorer social networks and supports, and feelings of helplessness (low
      mastery) mediating the link between SES and cortisol. However, we found no
      evidence for psychosocial or behavioral mediation of the association between race
      and cortisol response. CONCLUSIONS: Lower SES was associated in a graded fashion
      with flatter diurnal rhythms as a result of less of a decline during the evening.
      This association occurred independent of race and the data were consistent with
      mediation by health practices, emotional and social factors. Blacks also showed a
      flatter rhythm at the end of the day. This association was independent of SES and
      could not be explained by behavioral, social, or emotional mediators.

PMID- 16449412
TI  - Gender differences in associations of C-reactive protein with atherosclerotic
      risk factors and psychosocial characteristics in Japanese civil servants.
AB  - OBJECTIVE: Several prospective studies have demonstrated a direct association
      between high-sensitivity C-reactive protein (hsCRP) and the risks of developing
      cardiovascular disease. A strong sense of coherence (SOC) has also been
      associated with a reduced risk of cardiovascular mortality, but the underlying
      pathophysiologic mechanism remains unclear. We have evaluated the relationship of
      serum CRP and SOC and assessed the association of atherosclerotic risk factors
      with CRP in male and female subjects. METHODS: Data were collected in 2003 and
      2004 cross-sectionally from the two phases of a longitudinal study.
      Atherosclerotic risk factors were evaluated along with psychosocial
      characteristics for 1,339 apparently healthy civil servants (748 women and 591
      men) aged 20 to 60 years. The Japanese version of the SOC-13 was used in the
      study. RESULTS: After controlling for traditional atherosclerotic risk factors,
      SOC was inversely associated with hsCRP levels only in men. Among the
      atherosclerotic risk factors, body mass index and high-density lipoprotein
      cholesterol had the strongest associations with hsCRP in both sexes. Mean
      arterial pressure and blood glucose were positively correlated with hsCRP in men,
      and serum triglyceride levels positively correlated with hsCRP in women.
      CONCLUSION: The findings suggested that a higher SOC might be associated with
      lower serum CRP levels in men. Also, the association of traditional
      atherosclerotic risk factors with CRP was not equal in men and women.

PMID- 16449413
TI  - The role of angry rumination and distraction in blood pressure recovery from
      emotional arousal.
AB  - OBJECTIVE: Cardiovascular recovery of prestress baseline blood pressure has been
      implicated as a possible additional determinant of sustained blood pressure
      elevation. We hypothesize that angry ruminations may slow the recovery process.
      METHOD: A within-subjects design was used in which resting baseline blood
      pressure and heart rate measurements were assessed on 60 subjects, who then took
      part in two anger-recall tasks. After each task, subjects sat quietly and alone
      during a 12-minute recovery period randomized to with or without distractions.
      During baseline, task, and recovery, blood pressure was continuously monitored;
      during recovery, subjects reported their thoughts at five fixed intervals.
      RESULTS: Fewer angry thoughts were reported in the distraction condition (17%)
      compared with no distraction (31%; p = .002); an interaction showed that this
      effect was largely the result of the two intervals immediately after the anger
      recall task. Trait rumination interacted with distraction condition such that
      high ruminators in the no-distraction condition evidenced the poorest blood
      pressure recovery, assessed as area under the curve (p = .044 [systolic blood
      pressure] and p = .046 [diastolic pressure]). CONCLUSIONS: People who have a
      tendency to ruminate about past anger-provoking events may be at greater risk for
      target organ damage as a result of sustained blood pressure elevations; the
      effect is exacerbated when distractions are not available to interrupt the
      ruminative process.

PMID- 16449414
TI  - Violence exposure and optimism predict task-induced changes in blood pressure and
      pulse rate in a normotensive sample of inner-city black youth.
AB  - OBJECTIVE: This investigation examined the association of violence exposure (home
      and neighborhood) and optimism to task-induced changes in systolic blood pressure
      (SBP), diastolic blood pressure (DBP), and pulse rate (PR). METHODS: Drawn from a
      larger investigation, the convenience sample for this study consisted of 172
      normotensive black youth (mean age = 11.5 years, standard deviation = 1.3).
      Violence exposure and optimism were self-reported by participants, and task
      induced changes in SBP, DBP, and PR were measured with an automated monitor
      during two sequentially administered digit-forward and digit-backward tasks.
      RESULTS: Hierarchical regression analyses revealed that violence exposure was
      inversely related to task-induced changes in SBP (p = .010) and DBP (p = .005).
      Optimism was not an independent predictor of blood pressure or PR changes (p-s >
      .32). The final step of these hierarchical analyses indicated that the effects of
      violence exposure and optimism interacted to predict task-induced changes in SBP
      (p = .013) and PR (p = .003). Follow-up regression analyses indicated that
      violence exposure was inversely related to task-induced changes in SBP among
      participants high in optimism and was positively associated with PR reactivity in
      participants low in optimism. CONCLUSIONS: The youth in this study have intact
      mechanisms for buffering blood pressure responses to violence exposure,
      especially those who are more optimistic about their future-a person factor whose
      moderating effects might wane with advancing age.

PMID- 16449415
TI  - History of major depressive disorder and endothelial function in postmenopausal
      women.
AB  - OBJECTIVE: To determine whether history of depression is associated with
      endothelium-dependent flow-mediated dilation (FMD) in postmenopausal women.
      METHODS: Thirty-nine postmenopausal women with no known or suspected
      cardiovascular disease participated. Nineteen had a positive lifetime history of
      major depressive disorder, and 20 were never depressed. None were currently
      depressed, and all had been free of major depressive disorder and antidepressant
      medications for > or =1 year. History of depression was assessed with the
      Structured Clinical Interview for DSM-IV, enhanced by a modified version of the
      timeline follow-back method. Current depressive symptoms were measured with the
      Center for Epidemiological Studies Depression scale (CES-D). Brachial artery FMD
      was measured with ultrasound and calculated as percent dilation from baseline.
      RESULTS: After controlling for current subclinical depressive symptoms,
      ethnicity, hormone replacement therapy, and presence of the metabolic syndrome,
      previously depressed women showed significantly and clinically meaningful lower
      FMD than never depressed women. Controlling the same covariates, there was a dose
      response relationship between number of depressive episodes and FMD. Examination
      of FMD means showed a significant negative correlation between number of
      depressive episodes and FMD. CONCLUSION: In postmenopausal women, depression
      continues to show a negative relationship to endothelial functioning even after
      years of remission. This relationship is not accounted for by residual depressive
      symptoms. Implications pertain to exclusion of previously depressed persons from
      control groups in research exploring the relationship between depression and
      cardiovascular disease.

PMID- 16449416
TI  - Design and rationale for a randomized, controlled trial of interpersonal
      psychotherapy and citalopram for depression in coronary artery disease (CREATE).
AB  - OBJECTIVE: Recognition that depression is associated with increased morbidity and
      mortality in coronary artery disease (CAD) patients has augmented the need for
      evidence-based treatment guidelines. This article presents the design of a
      multisite, Canadian trial of the efficacy, safety, and tolerability of
      interpersonal psychotherapy (IPT), an empirically supported, depression-focused
      therapy, and the selective serotonin reuptake inhibitor citalopram, alone or in
      combination, in the treatment of major depression in CAD patients. METHODS: Two
      hundred eighty stable CAD patients with a current major depressive episode of at
      least 4 weeks' duration, based on the Structured Clinical Interview for
      Depression (SCID), and who have a baseline score >19 on a centralized, telephone
      administered, 24-item Hamilton Depression Rating Scale (HAM-D) will be randomly
      assigned to receive 12 weekly IPT sessions or 12 weekly sessions of standardized
      clinical management (CM). Patients are also randomly assigned to receive 20 to 40
      mg per day of citalopram or pill-placebo. This results in a 2-by-2 factorial
      design with four groups: IPT plus pill-placebo, IPT plus citalopram, CM plus pill
      placebo, and CM plus citalopram. This permits the evaluation of both IPT and
      citalopram. Blinded, centralized, 24-item, HAM-D telephone ratings constitute the
      primary outcome variable. The self-report Beck Depression Inventory-II is the
      secondary outcome. Analyses will involve the intent-to-treat principle with last
      observation carried forward for incomplete assessments. RESULTS: Not applicable.
      CONCLUSIONS: The results of this trial will contribute to the development of
      evidence-based clinical guidelines for managing depression in the context of CAD.

PMID- 16449417
TI  - Major depression and allergy: does neuroticism explain the relationship?
AB  - OBJECTIVE: To determine the association between major depression, neuroticism,
      and self-reported allergy among adults in the community. METHODS: Data were drawn
      from the Midlife Development in the United States Survey, a nationally
      representative sample of 3,032 adults age 25 to 74. ANOVA and multiple logistic
      regression analyses were used to determine the association between depression and
      allergy and the role of neuroticism in these relationships. These links were also
      examined by gender. RESULTS: Among adults in the community, major depression was
      associated with a significantly increased likelihood of allergy (odds ratio [OR],
      1.5; 95% confidence interval [CI], 1.14-1.98). Higher levels of neuroticism were
      also significantly associated with increased likelihood of allergy (OR, 1.22; 95%
      CI, 1.04-1.43). Among women, major depression was associated with a significantly
      increased likelihood of allergy (OR, 1.67; 95% CI, 1.15-2.41), and this
      relationship persisted after adjusting for demographic characteristics and
      neuroticism. Among men, there was no significant relationship between allergy and
      depression, yet neuroticism was related to allergy (OR, 1.42; 95% CI, 1.42-1.82),
      which persisted after adjustment for depression. CONCLUSION: These data are
      consistent with results of previous studies showing an association between major
      depression and allergy among adults and extend these data by providing
      preliminary evidence suggesting that this association is specific to women and
      independent of the effects of neuroticism among women. In addition, the data
      provide preliminary evidence that neuroticism may be related to allergy among
      men, though no link between depression and allergy was found among men. Future
      research with prospective, longitudinal studies is needed next to understand the
      possible biological underpinnings of these associations.

PMID- 16449418
TI  - Investigation of the serotonin transporter regulatory region polymorphism in
      bulimia nervosa: relationships to harm avoidance, nutritional parameters, and
      psychiatric comorbidity.
AB  - OBJECTIVE: Genes involved in 5HT transmission have been supposed to contribute to
      the biologic vulnerability for bulimia nervosa (BN). Because a long (L) and a
      short (S) variant of the promoter region of the 5HT transporter gene have been
      identified, we tested whether the 5HTT gene-linked polymorphic region (5HTTLPR)
      could represent a susceptibility factor for BN and/or could be related to
      nutritional parameters, harm avoidance personality dimension, and psychiatric
      comorbidity. METHODS: A total of 219 white women (125 bulimics and 94 healthy
      control subjects) underwent a blood sample collection for 5HTTLPR genotyping and
      a clinical evaluation assessing comorbidity for axis I and II psychiatric
      disorders, harm avoidance personality dimension, and body composition (only
      patients). RESULTS: The distribution of the 5HTTLPR genotypes did not
      significantly differ between patients and control subjects, although the L allele
      was significantly more frequent in the former. Bulimic individuals carrying at
      least one copy of the S allele had significantly lower mean body mass index and
      body fat mass values and significantly higher mean harm avoidance score than
      patients with the LL genotype. No significant association was found between the
      5HTTLPR genotype and comorbid axis I and II psychiatric disorders. CONCLUSIONS:
      These findings support the view that polymorphic variants of the 5HTT promoter
      region do not play a part in predisposing to BN, whereas they seem to predispose
      bulimic individuals to nutritional impairment and increased harm avoidance.

PMID- 16449419
TI  - Psychiatric morbidity and toxic burden in patients with environmental illness: a
      controlled study.
AB  - OBJECTIVE: Patients with environmental illness experience a large number of
      psychological symptoms. The nature of these symptoms and their pathogenesis
      (toxicogenic versus psychogenic) is controversial. The objective was to (1)
      characterize the nature of the psychological symptoms according to well
      established diagnostic criteria, and (2) to investigate the association between
      toxicological factors and psychological symptoms. METHODS: Toxic burden, somatic
      morbidity, and psychiatric morbidity were assessed in 309 outpatients with
      environmental illness and 59 semiconductor industry workers matched for age and
      gender. Psychiatric disorders were assessed by a structured psychiatric interview
      (SCID), and distress was assessed by the Symptom-Checklist-90-Revised (SCL-90-R).
      Routine and specific laboratory tests in blood and urine samples were used to
      assess chemical exposures. RESULTS: Overall psychiatric morbidity was
      significantly higher in patients than in controls according to SCID (75% versus
      24%). Somatoform, mood, and anxiety disorders were significantly more frequent in
      patients with environmental illness. They also revealed marked stress on the SCL
      90-R somatization subscale and scored significantly higher than controls on most
      of the other subscales. Industry workers from the control group tended to have
      higher urine metal concentrations than environmental illness patients and similar
      concentrations of solvents in blood. CONCLUSION: Our data extend previous
      findings of high psychiatric morbidity in patients with environmental illness.
      They do not support the notion of a direct causal link between chemical exposure
      and the psychological symptoms.

PMID- 16449420
TI  - Role of monitoring and blunting coping styles in primary insomnia.
AB  - OBJECTIVE: Primary insomnia is one of the most prevalent sleep disorders and
      assumed to be initiated and maintained, among other factors, by psychological
      variables such as coping strategies, sleep hygiene techniques, and arousability.
      Althouugh the number and kind of stressors seem to be important initiators of
      insomnia, individual coping dispositions appear to play a larger role in
      maintaining it. This study explores the relationship between different coping
      dispositions (monitoring/blunting) and insomnia. Monitoring refers to information
      seeking behavior under threat; blunting pertains to distractive strategies
      utilized in situations implying threat or danger. METHODS: The study compares 37
      primary insomniacs (DSM IV criteria) and 47 good sleepers. Dependent measures
      included self-rating scales concerning sleep quality (Schlaffragebogen part B,
      Frankfurter Schlaffragebogen), coping styles (Frankfurt Monitoring Blunting
      Scales), and psychopathology (Neo Five Factors Inventory, Beck Anxiety
      Inventory). All measures had documented psychometric properties. RESULTS: Primary
      insomniacs were significantly more likely to rigidly resort to monitoring
      strategies in controllable as well as uncontrollable situations. Further, 73% of
      all rigid monitors identified in the sample were rated as primary insomniacs,
      whereas 86% of all rigid Blunters were good sleepers. Insomniacs showed higher
      levels of anxiety than good sleepers, coping style groups differed in anxiety and
      neuroticism scores. CONCLUSION: The study further supports the hypothesis that a
      monitoring coping style is related to primary insomnia. Blunting appears to be a
      good predictor of high sleep quality. The results are discussed with regard to
      improving treatment for patients suffering from primary insomnia.

PMID- 16449421
TI  - Opioid analgesia in persons at risk for hypertension.
AB  - OBJECTIVE: Acute pain sensitivity is reduced in clinical hypertension, but the
      precise relationship between pain perception and altered blood pressure control
      is not well-characterized. A negative correlation between resting blood pressure
      and pain sensitivity is observed throughout the normotensive range, suggesting
      links between basic mechanisms of blood pressure control and pain regulation. The
      opioid peptides are important endogenous analgesic mechanisms, but their role in
      the hypoalgesia of blood pressure elevations has not been well-established. The
      current study sought to examine the effects of endogenous opioids on blood
      pressure-associated hypoalgesia in young adults at risk for hypertension
      development. METHODS: The effects of the opioid receptor antagonist, naltrexone,
      on cold pressor pain sensitivity were assessed in young adult men (n = 49) and
      women (n = 76) with mildly elevated casual blood pressure. RESULTS: Results
      indicate interactions between hypertension risk and the effects of opioid
      blockade on pain sensitivity. CONCLUSIONS: These findings suggest exaggerated
      opioid analgesia in persons at enhanced risk for hypertension and point to
      important links between altered neuropeptide regulation of pain and altered blood
      pressure control mechanisms in the early stages of hypertension.

PMID- 16449422
TI  - Ethnic differences in pain reports and the moderating role of depression in a
      community sample of Hispanic and Caucasian participants with serious health
      problems.
AB  - OBJECTIVE: The present study examined ethnic differences in pain reports between
      Hispanics (n = 147) and Caucasians (n = 1308) with serious health problems. It
      was predicted that Hispanics would report more pain in relation to their health
      problems than would Caucasians, depression would be associated with increased
      pain reports in both groups, and depression's influence on pain reports would be
      greater for Hispanics compared with Caucasians. METHODS: Data from Hispanic and
      Caucasian participants with a current health problem were utilized from the
      National Comorbidity Survey, a nationally representative epidemiological sample.
      Participants' pain reports, relative to their health problems, were obtained.
      Hierarchal regression analyses were conducted to examine the relationship between
      ethnicity and reported pain and the potentially moderating role of depression.
      RESULTS: Findings indicated that Hispanics reported more pain compared with
      Caucasians and that depression was associated with higher pain reports in both
      groups. Depression moderated the relationship between ethnicity and pain such
      that ethnic differences in pain reports were even greater among depressed
      participants than among nondepressed participants. That is, pain reports for
      Hispanics were higher in the presence of depression than was found for the
      Caucasian participants. CONCLUSIONS: Cultural differences in the acceptability
      and the expression of distress may be related to higher pain reports among
      Hispanics as compared with Caucasians, particularly in the presence of
      depression. The interplay of biological, psychological and sociocultural
      processes involved in both pain and depression were considered.

PMID- 16449423
TI  - Mapping the road from childhood trauma to adult somatization: the role of
      attachment.
AB  - OBJECTIVE: This study tested whether insecure attachment mediates the link
      between childhood trauma and adult somatization. METHODS: A community sample of
      101 couples completed self-report measures, including the Relationship Scales
      Questionnaire, the Childhood Trauma Questionnaire, the Somatic Symptom Inventory,
      the Beck Depression Inventory, and the Conflict Tactics Scale. RESULTS: Childhood
      trauma was associated with higher levels of somatization and insecure attachment.
      Insecure attachment style was also associated with higher levels of somatization.
      Controlling for age, income, and recent intimate partner violence, analyses
      showed that fearful attachment fully mediated the link between childhood trauma
      and somatization for women. For men, there was no such mediation, but both
      childhood trauma and insecure attachment styles made independent contributions to
      predicting levels of somatization. CONCLUSIONS: Findings are consistent with the
      hypothesis that, for women, childhood trauma influences adult levels of
      somatization by fostering insecure adult attachment. For men, findings suggest
      that trauma and attachment are both important independent predictors of adult
      somatization. Study results support the idea that childhood trauma shapes
      patients' styles of relating to others in times of need, and these styles, in
      turn, influence the somatization process and how patients respond to providers.
      Screening for attachment style may provide information that could allow health
      care providers to tailor treatment more effectively.

PMID- 16449424
TI  - The association between somatization and perceived ability: roles in dysmenorrhea
      among Israeli Arab adolescents.
AB  - OBJECTIVE: The aim of this study was to investigate whether somatization and
      attitudes toward menstruation predict the incidence of pain intensity and
      dysmenorrhea among Israeli Arab adolescent females. METHODS: Participants were
      160 Israeli Arab adolescents, including 50 Muslims, 50 Christians, and 60 Druze.
      A 20-item questionnaire was used to assess attitudes regarding menstruation. The
      short version of the Brief Symptom Inventory was used to measure the level of
      somatization. RESULTS: Factor analysis of the Attitudes Toward Menstruation
      Instrument revealed two significant composites: perceived ability and impurity
      during menstruation. High levels of somatization predicted pain intensity and low
      levels of perceived ability predicted the prevalence of dysmenorrhea. Although
      the Israeli Muslim adolescents revealed higher levels of somatization as compared
      with their Christian and Druze counterparts and the Druze revealed the lowest
      levels of perceived ability compared with the other subgroups, no significant
      role for ethnicity and impurity was found. No differences were found between
      groups in scores of menstrual pain and prevalence of dysmenorrhea. Higher levels
      of somatization and lower levels of perceived ability, as well as a greater
      portion of Muslim and Druze and higher levels of religiosity, were found among
      rural residents. CONCLUSIONS: The role of cultural variables and personality
      traits in the complexity of dysmenorrhea as a socio-bio-psychological phenomenon
      is proposed in light of contemporary interactive models. It is suggested that
      within the Israeli Arab minorities the impact of cultural background on health
      affects more the perceptual and cognitive levels and are not generalized to overt
      behavior and morbidity such as dysmenorrhea.

PMID- 16449425
TI  - Randomized clinical trial of cognitive behavioral stress management on human
      immunodeficiency virus viral load in gay men treated with highly active
      antiretroviral therapy.
AB  - OBJECTIVE: Human Immunodeficiency Virus (HIV)-positive individuals treated with
      highly active antiretroviral therapy (HAART) may experience psychological burdens
      and negative mood states, which could impair their ability to derive maximum
      benefits from their medical treatment. We tested whether a cognitive behavioral
      stress management (CBSM) intervention in combination with antiretroviral
      medication adherence training (MAT) from a clinical pharmacist influences HIV
      viral load more than MAT alone. METHODS: HIV-positive men who have sex with men
      were randomized to either a 10-week CBSM + MAT intervention (n = 76) or a MAT
      Only condition (n = 54). Data were collected at baseline immediately following
      the 10-week intervention period, at 9 months postrandomization, and at 15 months
      postrandomization. RESULTS: We found no differences in HIV viral load among the
      130 men randomized. However, in the 101 men with detectable viral load at
      baseline, those randomized to CBSM + MAT (n = 61) displayed reductions of 0.56
      log10 units in HIV viral load over a 15-month period after controlling for
      medication adherence. Men in the MAT-Only condition (n = 40) showed no change.
      Decreases in depressed mood during the intervention period explained the effect
      of CBSM + MAT on HIV viral load reduction over the 15 months. CONCLUSIONS: A time
      limited CBSM + MAT intervention that modulates depressed mood may enhance the
      effects of HAART on suppression of HIV viral load in HIV+ men with detectable
      plasma levels.

PMID- 16449427
TI  - Association between nocturnal vagal tone and sleep depth, sleep quality, and
      fatigue in alcohol dependence.
AB  - BACKGROUND: This study examined whether nocturnal vagal tone as indexed by the
      high-frequency (HF) power component of heart rate variability is related to
      measures of sleep depth and daytime perceptions of sleep quality, sleepiness, and
      fatigue in alcohol dependence. METHODS: Abstinent alcohol-dependent patients (n =
      14) and comparison control subjects (n = 14) underwent all-night polysomnography
      along with assessment of heart rate variability during an awake period before
      sleep and during sleep. Sleep-quality perceptions, along with self-reported
      sleepiness and levels of energy and fatigue, were obtained in the morning.
      RESULTS: As compared with control subjects, alcohol-dependent persons showed
      marked decreases in delta sleep along with impairments of sleep quality and
      daytime energy. In addition, alcoholics showed a decrease of the HF power
      component of heart rate variability during the awake period before sleep and
      during nocturnal sleep as compared with control subjects. HF power during the
      awake period before sleep correlated with electroencephalographic delta sleep and
      delta power observed during the subsequent sleep period. HF power during the
      awake period before sleep also correlated with morning reports of sleep quality,
      sleepiness, and fatigue. CONCLUSIONS: Alcohol dependence compromises vagal output
      measured before sleep onset, which correlates with loss of delta sleep and with
      morning reports of sleep impairments. Testing of interventions that target
      sympathovagal balance might identify new strategies for partial amelioration of
      the sleep disturbances and impairments in daytime functioning observed in persons
      with alcohol dependence.

PMID- 16449426
TI  - Mental and physical comorbid conditions and days in role among persons with
      arthritis.
AB  - OBJECTIVE: To estimate the prevalence of comorbidity among people with arthritis
      in the US adult population and to determine the role of comorbidity in accounting
      for the association of arthritis with days out of role (a measure of inability to
      work or carry out normal activities). METHODS: Data come from the National
      Comorbidity Survey Replication (NCS-R), a nationally representative household
      survey of 9,282 respondents ages 18 and older carried out in 2001 to 2003.
      Arthritis was assessed by self-report in a chronic-conditions checklist, along
      with a wide range of other physical conditions. Mental and substance use
      disorders were ascertained with the World Health Organization Composite
      International Diagnostic Interview (CIDI). Number of days out of role was
      assessed for the 30 days before the interview. RESULTS: Arthritis was reported by
      27.3% of respondents, 80.9% of whom also reported at least one other physical or
      mental disorder, including 45.6% with another chronic pain condition, 62.3% with
      another chronic physical condition, and 24.3% with a 12-month mental disorder.
      Arthritis was significantly associated with days out of role, but comorbidity
      explained more than half of this association. No significant interactions were
      found between arthritis and the other conditions in predicting days out of role.
      CONCLUSION: Comorbidity is the rule rather than the exception among people with
      arthritis. Comorbidity accounts for most of the days out of role associated with
      arthritis. The societal burden of arthritis needs to be understood and managed
      within the context of these comorbid conditions.

PMID- 16449429
TI  - Please don't talk bad about good old Aunt ANOVA!: a reply to A.J. Vickers'
      critique.

PMID- 16449428
TI  - Psychosocial influences on women's experience of planned elective cesarean
      section.
AB  - OBJECTIVE: The successful management of pain from normal or interventional
      delivery is an important part of women's experience of childbirth. Our objective
      was to examine psychosocial factors (expectations, control beliefs, anxiety
      sensitivity) as measured in mothers and birth partners before an elective
      cesarean section. We focused on the impact that these variables have on maternal
      fear and pain during and after delivery. METHODS: Sixty-five women booked for an
      awake cesarean section with a regional nerve block and their birth partners were
      recruited. Data were collected at three time points for the mothers, before,
      during the cesarean section and after delivery on the postnatal ward, and at two
      time points for the birth partners (before and during the cesarean section).
      RESULTS: Maternal fear responses varied during the operation, in that fear was
      greatest at the point of administration of the nerve block. Within mothers,
      preoperative negative expectations were related to fear experiences during
      delivery, which was in turn related to their postoperative pain. Maternal anxiety
      sensitivity was found to mediate the relationship between negative expectations
      and fear, whereas birth partner's fear mediated between maternal fear and
      postoperative pain. Mothers' prenatal perceptions of control over drugs predicted
      their postoperative pain. CONCLUSIONS: Maternal fear during cesarean section not
      only fluctuates, but may be influenced by psychosocial factors, including their
      birth partner. Psychosocial factors were also important predictors of
      postoperative experiences. Interventions that appropriately manage psychological
      and social factors during cesarean delivery may facilitate a more positive
      experience for mothers.

PMID- 16449432
TI  - Notification that new names and new combinations have appeared in volume 55, part
      6, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles). Taxonomic opinions included in
      this List (i.e. the creation of synonyms or the emendation of circumscriptions)
      cannot be considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission.

PMID- 16449433
TI  - Krokinobacter gen. nov., with three novel species, in the family
      Flavobacteriaceae.
AB  - Five strains belonging to the family Flavobacteriaceae were isolated from marine
      sediment samples collected in Sagami and Tokyo bays on the Pacific coastline of
      Japan. The five isolates formed a coherent and novel genus-level lineage within
      the family Flavobacteriaceae. The most closely related species with a validly
      published name was Cellulophaga lytica. The five isolates were rod-shaped, Gram
      negative, aerobic, catalase- and oxidase-positive, flexirubin-negative and yellow
      pigmented. The dominant fatty acids were branched or hydroxy acids, i.e. i
      C(15:0), i-C(15:1) and i-C(17:0) 3-OH. These strains degraded gelatin, casein,
      DNA and Tween 80. The G+C content of their DNAs ranged between 33 and 39 mol%.
      Although analysis of the 16S rRNA gene sequence similarity divided these strains
      into two subgroups with a 2.3% sequence difference, the results of DNA-DNA
      hybridization indicated the grouping of these strains into three distinct
      species. On the basis of phenotypic and genotypic analyses, the novel genus
      Krokinobacter is proposed, with Krokinobacter genikus sp. nov., containing three
      of the strains, as the type species. The type strain is Cos-13T (=NBRC
      100811T=CIP 108744T). The names Krokinobacter eikastus sp. nov. (type strain PMA
      26T=NBRC 100814T=CIP 108743T) and Krokinobacter diaphorus sp. nov. (type strain
      MSKK-32T=NBRC 100817T=CIP 108745T) are proposed for the other two isolates.

PMID- 16449434
TI  - Pediococcus stilesii sp. nov., isolated from maize grains.
AB  - A Gram-positive, coccus-shaped, lactic acid bacterium, strain LMG 23082T, was
      isolated from steeped maize grains. The organism is homofermentative and produces
      D- and L-lactic acid from glucose. 16S rRNA gene sequence analysis revealed that
      the organism belongs to the genus Pediococcus, with Pediococcus pentosaceus and
      Pediococcus acidilactici as nearest neighbours. Genotypic fingerprinting, whole
      cell protein electrophoresis, DNA-DNA hybridizations and physiological and
      biochemical tests allowed differentiation of strain LMG 23082T from other
      established Pediococcus species. A remarkable feature was that, unlike other
      pediococci, this bacterium was capable of growth at pH 9.0. The strain studied
      represents a novel species for which the name Pediococcus stilesii sp. nov. is
      proposed with the type strain LMG 23082T (=BFE 1652T=FAIR-E 180T=CCUG 51290T),
      the only currently known isolate of the species.

PMID- 16449435
TI  - Thorsellia anophelis gen. nov., sp. nov., a new member of the
      Gammaproteobacteria.
AB  - A Gram-negative, rod-shaped organism (CCUG 49520T) was isolated from the midgut
      of the mosquito Anopheles arabiensis. 16S rRNA gene sequence analysis
      demonstrated that this isolate is unique, showing <93% similarity to species of
      the families Enterobacteriaceae and Vibrionaceae. The quinone system consisted
      exclusively of ubiquinone Q-8; the polar lipid profile consisted of the major
      compounds phosphatidylethanolamine and phosphatidylglycerol, a moderate to minor
      amount of two unknown aminophospholipids, an unknown phospholipid and two unknown
      polar lipids; the polyamine pattern was characterized by the predominant compound
      1,3-diaminopropane and showed some significant differences when compared with
      members of the Enterobacteriaceae and Vibrionaceae. On the basis of 16S rRNA gene
      sequence analysis in combination with chemotaxonomic data, strain CCUG 49520T is
      considered to represent a new genus and species, for which the name Thorsellia
      anophelis gen. nov., sp. nov. is proposed. The type strain is CCUG 49520T (=CIP
      108754T).

PMID- 16449436
TI  - Methylobacterium adhaesivum sp. nov., a methylotrophic bacterium isolated from
      drinking water.
AB  - A pink-pigmented, facultatively methylotrophic strain, AR27T, isolated from the
      drinking water distribution system of Seville, Spain, was characterized
      taxonomically. Cells were Gram-negative rods, motile, non-spore-forming and
      strictly aerobic. Growth in liquid media was flocculant whereas on solid media
      growth produced colonies that usually adhered to the agar surface. On the basis
      of its phenotypic characteristics, 16S rRNA gene sequence data and DNA G+C
      content (63.6 mol%), strain AR27T (=CECT 7069T=CCM 7305T) is proposed as the type
      strain of a novel species of the genus Methylobacterium, Methylobacterium
      adhaesivum sp. nov.

PMID- 16449437
TI  - Pseudovibrio ascidiaceicola sp. nov., isolated from ascidians (sea squirts).
AB  - Two bacterial strains, F423T and F10102, were isolated from two ascidians,
      Polycitor proliferus and Botryllidae sp., respectively, which were collected from
      a beach on the Boso peninsula in Japan. Cells of both isolates were motile, rod
      shaped and formed star-shaped aggregates in the early stage of exponential
      growth, but were coccoid in stationary growth phase. The results of 16S rRNA gene
      sequence analysis, fatty acid analysis, DNA-DNA hybridization experiments and
      physiological and biochemical tests indicated that the two strains were members
      of a novel species of the genus Pseudovibrio for which the name Pseudovibrio
      ascidiaceicola sp. nov. is proposed. The type strain is F423T (=NBRC 100514T=IAM
      15084T=DSM 16392T=KCTC 12308T).

PMID- 16449438
TI  - Bacillus macauensis sp. nov., a long-chain bacterium isolated from a drinking
      water supply.
AB  - A novel long-chain, Gram-positive, rod-shaped, endospore-forming strain was
      isolated from the influent of a drinking water treatment plant in Macau, China.
      This facultatively anaerobic isolate (2.0-5.0 microm in length and 0.8-1.2 microm
      in diameter) formed long chains over 100 microm in length in both liquid and
      solid media. It had a growth temperature range of 20-40 degrees C, with an
      optimum at about 30 degrees C, and a growth pH range of 6.0-10.0, with an optimum
      at pH 8.5. The G+C content of the DNA extracted was 40.8 mol%. The main fatty
      acid components were anteiso-C(15:0) (67.2%) and iso-C(15:0) (21.7%), with small
      quantities of iso-C(14:0), C(14:0), iso-C(16:0) and iso-C(17:0). The main quinone
      component was MK-7. Phylogenetic analyses based on its 16S rRNA gene sequence
      revealed that this isolate is a member of the genus Bacillus, with no close
      relatives at the species level (sequence similarity <96.1%). These phenotypic and
      genetic properties suggested that this strain represents a novel species, for
      which the name Bacillus macauensis sp. nov. is proposed. The type strain is ZFHKF
      1T (=JCM 13285T=DSM 17262T).

PMID- 16449439
TI  - Lactobacillus suntoryeus Cachat and Priest 2005 is a later synonym of
      Lactobacillus helveticus (Orla-Jensen 1919) Bergey et al. 1925 (Approved Lists
      1980).
AB  - Strain R0052, isolated from a North American dairy starter culture, was initially
      identified as Lactobacillus acidophilus based on phenotypic analyses. However,
      upon sequencing the 16S rRNA gene, it became clear that the isolate was very
      highly related to Lactobacillus suntoryeus, Lactobacillus helveticus and
      Lactobacillus gallinarum, as similarities ranging from 99.3 to 99.8 % were
      observed. As an initial screening test to investigate the relatedness of strain
      R0052 and reference strains of L. suntoryeus, L. helveticus and L. gallinarum,
      the partial sequences for the genes encoding the alpha subunit of ATP synthase
      (atpA), RNA polymerase alpha subunit (rpoA), phenylalanyl-tRNA synthase alpha
      subunit (pheS), the translational elongation factor Tu (tuf), a surface-layer
      protein (slp) and the Hsp60 chaperonins (groEL) were determined and they revealed
      high relatedness between all of the strains. The determination of the 16S-23S
      rRNA internally transcribed spacer (ITS) sequences revealed 98.3-100% similarity
      between L. suntoryeus and L. helveticus strains. SDS-PAGE of whole-cell proteins
      did not distinguish between these species. Fluorescent amplified fragment length
      polymorphism (FAFLP) could distinguish between these taxa, but they still
      constituted a single cluster within the L. acidophilus group. Finally, DNA-DNA
      hybridization experiments between strain R0052 and the type strains of L.
      helveticus and L. suntoryeus yielded reassociation values above 70% and confirmed
      that these names are synonyms.

PMID- 16449440
TI  - Marinomonas polaris sp. nov., a psychrohalotolerant strain isolated from coastal
      sea water off the subantarctic Kerguelen islands.
AB  - Two aerobic, psychrohalotolerant, motile bacterial isolates, CK13T and CK16,
      isolated from sea-water samples collected off the subantarctic Kerguelen island,
      were characterized by using a polyphasic taxonomic approach. On the basis of 16S
      rRNA gene sequence data, the strains were 99.6% similar and exhibited 93-97%
      similarity with the seven recognized species of Marinomonas. The most closely
      related species were Marinomonas pontica and Marinomonas primoryensis, with 97
      and 96 % similarity at the 16S rRNA gene sequence level, respectively. DNA-DNA
      hybridization values between strain CK13T and M. pontica and M. primoryensis were
      only 58 and 40%, respectively. The major fatty acids present in strain CK13T were
      iso-C(16:0), C(16:0), C(16:1)omega7c and C(18:1)omega7c. The DNA G+C content of
      strain CK13T was 41.2 mol%. Phosphatidylethanolamine and phosphatidylglycerol
      were identified as the predominant phospholipids. All the above characteristics
      support the affiliation of strain CK13T to the genus Marinomonas. Phylogenetic
      analysis and phenotypic and genotypic distinctiveness confirmed that strains
      CK13T and CK16 are members of a novel species of the genus Marinomonas, for which
      the name Marinomonas polaris sp. nov. is proposed. The type strain is CK13T
      (=MTCC 6645T=DSM 16579T=JCM 12522T).

PMID- 16449441
TI  - Thalassomonas loyana sp. nov., a causative agent of the white plague-like disease
      of corals on the Eilat coral reef.
AB  - The taxonomic position of the coral pathogen strain CBMAI 722T was determined on
      the basis of molecular and phenotypic data. We clearly show that the novel
      isolate CBMAI 722 T is a member of the family Colwelliaceae, with Thalassomonas
      ganghwensis as the nearest neighbour (95 % 16S rRNA gene sequence similarity).
      CBMAI 722T can be differentiated from its nearest neighbour on the basis of
      phenotypic and chemotaxonomic features, including the utilization of cellobiose
      and L-arginine, the production of alginase and amylase, but not oxidase, and the
      presence of the fatty acids 12:0 3-OH and 14:0, but not 10:0 or 15:0. The DNA G+C
      content of CBMAI 722T is 39.3 mol%. We conclude that this strain represents a
      novel species for which we propose the name Thalassomonas loyana sp. nov., with
      the type strain CBMAI 722T (=LMG 22536T). This is the first report of the
      involvement of a member of the family Colwelliaceae in coral white plague-like
      disease.

PMID- 16449442
TI  - Tepidimicrobium ferriphilum gen. nov., sp. nov., a novel moderately thermophilic,
      Fe(III)-reducing bacterium of the order Clostridiales.
AB  - A moderately thermophilic, anaerobic bacterium (strain SB91T) was isolated from a
      freshwater hot spring at Barguzin Valley, Buryatiya, Russia. Cells of strain
      SB91T were straight to slightly curved rods, 0.5-0.6 microm in diameter and 3.0
      7.0 mum in length. Formation of endospores was not observed. The temperature
      range for growth was 26-62 degrees C, with an optimum at 50 degrees C. The pH
      range for growth was 5.5-9.5, with an optimum at pH 7.5-8.0. The substrates
      utilized by strain SB91T in the presence of 9,10-anthraquinone 2,6-disulfonate
      included peptone, tryptone, Casamino acids, yeast extract, beef extract, casein
      hydrolysate, alanine plus glycine, alanine plus proline, L-valine and n-propanol.
      Carbohydrates were not utilized. Strain SB91T reduced amorphous Fe(III) oxide,
      Fe(III) citrate, Fe(III) EDTA or Fe(III) nitrilotriacetate with peptone, L-valine
      or n-propanol as an electron donor. Strain SB91T reduced 9,10-anthraquinone 2,6
      disulfonate, thiosulfate, elemental sulfur, fumarate and selenite. Strain SB91T
      survived after exposure to gamma-radiation at a dose of 5.4 kGy. The G+C content
      of the DNA of strain SB91T was 33 mol%. Analysis of the 16S rRNA gene sequence
      revealed that the isolated organism belonged to cluster XII of the clostridia. On
      the basis of its physiological properties and the results of phylogenetic
      analyses, it is proposed that strain SB91T represents the sole species of a novel
      genus, Tepidimicrobium; the name Tepidimicrobium ferriphilum gen. nov., sp. nov.
      is proposed, with strain SB91T (=DSM 16624T=VKM B-2348T) as the type strain.

PMID- 16449443
TI  - Bacillus salarius sp. nov., a halophilic, spore-forming bacterium isolated from a
      salt lake in China.
AB  - A moderately halophilic bacterium, strain BH169T, capable of growing at
      salinities of 3-20% (w/v) NaCl was isolated from a saline lake in China. Strain
      BH169T was strictly aerobic, short-rod-shaped and non-motile (non-flagellated).
      Its major cellular fatty acids were anteiso-C15:0, anteiso-C17:0, iso-C15:0 and
      iso-C16:0. The genomic DNA G+C content was about 43 mol% and the predominant
      quinone was MK-7. The cell-wall peptidoglycan was of the A1gamma type, containing
      meso-diaminopimelic acid as the diagnostic diamino acid. Phylogenetic analysis
      based on 16S rRNA gene sequences showed that the isolate formed a distinct
      phylogenetic line within the spore-forming rods of the genus Bacillus. The levels
      of 16S rRNA gene sequence similarity to the type strains of Bacillus species were
      below 93%. On the basis of phenotypic and molecular properties, strain BH169T
      (=KCTC 3912T=DSM 16461T) represents the type strain of a novel species within the
      genus Bacillus, for which the name Bacillus salarius sp. nov. is proposed.

PMID- 16449444
TI  - Extremely halophilic denitrifying bacteria from hypersaline inland lakes,
      Halovibrio denitrificans sp. nov. and Halospina denitrificans gen. nov., sp.
      nov., and evidence that the genus name Halovibrio Fendrich 1989 with the type
      species Halovibrio variabilis should be associated with DSM 3050.
AB  - Anaerobic enrichments with acetate as electron donor and nitrate as electron
      acceptor at 4 M NaCl from inland, hypersaline lake sediments from Central Asia
      resulted in the isolation of several extremely halophilic bacteria that comprised
      two subgroups, most with vibrio-shaped cells and a single strain with rod-shaped
      cells. Members of both subgroups were extremely halophilic, with growth occurring
      in 2-5 M NaCl with an optimum at 2-3 M. 16S rRNA gene sequence analysis showed a
      close affiliation of the new isolates with Pseudomonas halophila DSM 3050 in the
      Gammaproteobacteria. However, phenotypic comparison of the denitrifying
      halophiles with the original description of P. halophila demonstrated that they
      were more similar to another bacterium isolated from the same source at the same
      time, the extremely halophilic Halovibrio variabilis, which has since been
      reclassified as Halomonas variabilis (DSM 3051). Direct cross-comparison showed
      that the characteristics of these two halophilic bacteria do not correspond with
      the original descriptions associated with these names and DSM numbers. While it
      is desirable that this problem be solved, in connection with the present
      investigations, this is a matter that can only be solved by a Request for an
      Opinion. On the basis of the phenotypic and genetic comparison of these isolates,
      it is proposed that the new denitrifying vibrio-shaped isolates represent a novel
      species, Halovibrio denitrificans sp. nov. (type strain HGD 3T=DSM 15503T=UNIQEM
      U232T) and that the rod-shaped isolate represents a novel genus and species,
      Halospina denitrificans gen. nov., sp. nov. (type strain HGD 1-3T=DSM
      15505T=UNIQEM U233T).

PMID- 16449445
TI  - Janibacter anophelis sp. nov., isolated from the midgut of Anopheles arabiensis.
AB  - A Gram-positive, aerobic, non-motile strain, H2.16BT, isolated from the midgut of
      the mosquito Anopheles arabiensis was investigated using a polyphasic approach.
      On the basis of 16S rRNA gene sequence similarity studies, strain H2.16BT was
      shown to belong to the genus Janibacter, being most closely related to Janibacter
      melonis (98.3%), Janibacter terrae (98.5%) and Janibacter limosus (98.5%).
      Chemotaxonomic data (meso-diaminopimelic acid as the diagnostic diamino acid in
      the cell wall and major fatty acids of iso-C16:0, C17:1omega8c and C17:0))
      supported the allocation of the strain to the genus Janibacter. The results of
      DNA-DNA hybridization and physiological and biochemical tests allowed the
      genotypic and phenotypic differentiation of strain H2.16BT from closely related
      species. Thus, H2.16BT represents a novel species of the genus Janibacter, for
      which the name Janibacter anophelis sp. nov. is proposed. The type strain is
      H2.16BT (=CCUG 49715T=CIP 108728T).

PMID- 16449446
TI  - Three novel species of the genus Catellatospora, Catellatospora chokoriensis sp.
      nov., Catellatospora coxensis sp. nov. and Catellatospora bangladeshensis sp.
      nov., and transfer of Catellatospora citrea subsp. methionotrophica Asano and
      Kawamoto 1988 to Catellatospora methionotrophica sp. nov., comb. nov.
AB  - Three Gram-positive, aerobic, non-motile, mesophilic strains, designated 2
      25(1)T, 2-29(17)T and 2-70(23)T, were isolated from sandy soil from Chokoria,
      Cox's Bazar, Bangladesh. The organisms produce short chains of non-motile spores
      that emerge singly or in tufts from vegetative hyphae on the surface of agar
      media. A comparative phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the isolates formed a distinct clade within the evolutionary
      radiation of the family Micromonosporaceae and clustered with members of the
      genus Catellatospora. The nearest neighbours were Catellatospora citrea subsp.
      citrea and C. citrea subsp. methionotrophica. Chemotaxonomic data, such as the
      presence of meso- and 3-hydroxy-diaminopimelic acids, N-glycolyl type muramic
      acid, arabinose and xylose and glucose in whole-cell hydrolysates,
      phosphatidylethanolamine as a diagnostic phospholipid, a tetrahydrogenated
      menaquinone with 9 isoprene units as a major menaquinone and fatty acid profiles
      predominated by iso-branched hexadecanoic acid and iso-branched pentadecanoic
      acid, supported the affiliation of the novel isolates to the genus
      Catellatospora. The results of DNA-DNA hybridization and physiological and
      biochemical tests allowed the novel isolates to be differentiated genotypically
      and phenotypically from the three recognized Catellatospora species. The three
      isolates therefore represent novel species for which the names Catellatospora
      chokoriensis sp. nov. [type strain 2-25(1)T=JCM 12950T=DSM 44900T],
      Catellatospora coxensis sp. nov. [type strain 2-29(17)T=JCM 12951T=DSM 44901T]
      and Catellatospora bangladeshensis sp. nov. [type strain 2-70(23)T=JCM 12949T=DSM
      44899T], are proposed. DNA-DNA hybridization tests with C. citrea subsp. citrea
      and C. citrea subsp. methionotrophica, in combination with chemotaxonomic and
      physiological data, demonstrated that C. citrea subsp. methionotrophica should be
      elevated to a separate species for which the name Catellatospora methionotrophica
      sp. nov., comb. nov. is proposed (type strain JCM 7543T=DSM 44098T).

PMID- 16449447
TI  - Patulibacter minatonensis gen. nov., sp. nov., a novel actinobacterium isolated
      using an agar medium supplemented with superoxide dismutase, and proposal of
      Patulibacteraceae fam. nov.
AB  - A novel Gram-positive bacterial strain, designated KV-614T, was isolated from a
      soil sample using an agar medium supplemented with superoxide dismutase. Based on
      16S rRNA gene sequence analysis, it was found that the strain represented a novel
      deep-rooting lineage within the class Actinobacteria and clustered with yet
      uncultivated bacteria from terrestrial environments and some unidentified strains
      isolated by unique methods. The most closely related established genus was
      Conexibacter (92.4% sequence similarity to Conexibacter woesei DSM 14684T). Cells
      of strain KV-614T were rod-shaped and motile with long flagella. The strain was
      catalase-positive, oxidase-negative and grew under aerobic conditions. The cell
      wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino
      acid and alanine and glutamic acid. The peptidoglycan acyl type was acetyl. The
      only detected isoprenoid quinone was demethylmenaquinone with seven isoprene
      units (DMK-7). Mycolic acids were not detected. The predominant cellular fatty
      acid was omega9c-octadecenoic acid (C18:1omega9c). Minor components were 12
      methyl tetradecanoic acid (anteiso-C15:0) and 14-methyl hexadecanoic acid
      (anteiso-C17:0). The DNA G+C content was 72 mol%. On the basis of phenotypic and
      genotypic characteristics, it is proposed that strain KV-614T represents a new
      genus and a novel species, Patulibacter minatonensis gen. nov., sp. nov., in the
      class Actinobacteria. The type strain is KV-614T (=NRRL B-24346T=JCM 12834T=NBRC
      100761T). The creation of the family Patulibacteraceae fam. nov. is proposed to
      encompass the genus Patulibacter gen. nov.

PMID- 16449449
TI  - Reclassification of Enterococcus flavescens Pompei et al. 1992 as a later synonym
      of Enterococcus casseliflavus (ex Vaughan et al. 1979) Collins et al. 1984 and
      Enterococcus saccharominimus Vancanneyt et al. 2004 as a later synonym of
      Enterococcus italicus Fortina et al. 2004.
AB  - The taxonomic relatedness between the species Enterococcus casseliflavus and
      Enterococcus flavescens and between Enterococcus italicus and Enterococcus
      saccharominimus was investigated. Literature data had already indicated the
      synonymy between E. casseliflavus and E. flavescens, but this observation had not
      been formally published. Additional evidence that the two taxa represent a single
      species was provided by comparison of the partial sequences for three
      housekeeping genes, phenylalanyl-tRNA synthase alpha subunit (pheS), RNA
      polymerase alpha subunit (rpoA) and the alpha subunit of ATP synthase (atpA).
      Additional genomic data derived from DNA-DNA hybridization demonstrated that the
      two species are synonymous. For E. italicus and E. saccharominimus, two recently
      described taxa, a high 16S rRNA gene sequence similarity of >99% and analogous
      phenotypic features indicated a close taxonomic relatedness. The same multilocus
      sequence analysis scheme for the three housekeeping genes was also applied for E.
      italicus and E. saccharominimus and indicated possible conspecificity, an
      observation that was also confirmed by a high DNA-DNA hybridization value
      (>or=78%). Data from the present study led to the proposal that E. flavescens
      should be reclassified as a later synonym of E. casseliflavus and that E.
      saccharominimus should be reclassified as a later synonym of E. italicus.

PMID- 16449448
TI  - Kribbella lupini sp. nov., isolated from the roots of Lupinus angustifolius.
AB  - Strain LU14T, isolated from the roots of Lupinus angustifolius, was characterized
      using a polyphasic approach. 16S rRNA gene sequence studies showed a similarity
      of 98.7% to the corresponding sequence of Kribbella sandramycini DSM 15626T.
      Chemotaxonomic data gathered for fatty acids, phospholipids, cell-wall
      peptidoglycan and menaquinones strongly supported the classification of this
      strain in the genus Kribbella and DNA-DNA hybridization studies suggested that it
      may represent a novel species. Many physiological features were found that
      clearly distinguished isolate LU14T from other Kribbella species. Based on the
      above data, a novel species of the genus Kribbella, Kribbella lupini sp. nov., is
      proposed with the type strain LU14T (=DSM 16683T=LMG 22957T).

PMID- 16449450
TI  - Roseibacterium elongatum gen. nov., sp. nov., an aerobic, bacteriochlorophyll
      containing bacterium isolated from the west coast of Australia.
AB  - A novel aerobic, chemoheterotrophic, bacteriochlorophyll-containing bacterium,
      strain OCh 323T, was isolated from sand at Monkey Mia, Shark Bay, located on the
      west coast of Australia. The cells were Gram-negative, non-motile rods of
      variable length; one or both cell poles was narrower. Bacteriochlorophyll a was
      synthesized under aerobic conditions. Catalase, oxidase and urease were produced.
      The ONPG reaction was positive. The major component of the cellular fatty acid
      was octadecenoic acid (18:1). The DNA G+C content was 68.1 mol%. The results of
      16S rRNA gene sequence comparisons revealed that strain OCh 323T formed a novel,
      separate line of descent within the alpha-3 group of the Alphaproteobacteria. The
      similarity value for the 16S rRNA gene sequence of strain OCh 323T and that of
      the most closely related species, Rhodovulum sulfidophilum, was 91.4%. It is
      concluded that strain OCh 323T (=JCM 11220T=CIP 107377T) should be placed in a
      novel genus, Roseibacterium gen. nov., as the type strain of a novel species
      Roseibacterium elongatum sp. nov.

PMID- 16449451
TI  - Microbacterium koreense sp. nov., from sea water in the South Sea of Korea.
AB  - Microbacterium strains JS53-2T and JS53-5 were isolated from sea water in the
      South Sea of Korea and subjected to phenotypic, chemotaxonomic and genetic
      characterization. The cells were found to be Gram-positive. These strains
      contained MK-11 and MK-12 as the main respiratory quinones and anteiso-C15:0,
      anteiso-C17:0 and iso-C16:0 as the major cellular fatty acids. The DNA G+C
      content was 68 mol%. The cell-wall sugars of the isolates were galactose and
      xylose, and the diamino acid in the cell-wall hydrolysates was lysine.
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolates
      represented an evolutionary lineage distinct from those of other Microbacterium
      species. DNA-DNA reassociation values between the isolates and reference strains
      Microbacterium terregens KCTC 19034T, Microbacterium lacticum KCTC 9230T,
      Microbacterium aurum KCTC 19091T and Microbacterium schleiferi KCTC 19095T were
      below 23%. On the basis of evaluation of the morphological, physiological and
      chemotaxonomic characteristics, 16S rRNA gene sequence comparisons and DNA-DNA
      hybridizations, a novel species, Microbacterium koreense sp. nov., is proposed
      for these isolates. The type strain is JS53-2T (=KCTC 19074T=CIP 108696T=CCUG
      50754T).

PMID- 16449453
TI  - Chryseobacterium soldanellicola sp. nov. and Chryseobacterium taeanense sp. nov.,
      isolated from roots of sand-dune plants.
AB  - Two Gram-negative, yellow-pigmented bacteria designated PSD1-4T and PHA3-4T,
      isolated from two sand-dune plant species inhabiting coastal areas in Tae-an,
      Korea, were subjected to taxonomic investigation. 16S rRNA gene sequence analysis
      indicated that both isolates should be placed in the genus Chryseobacterium of
      the family Flavobacteriaceae. The phenotypic properties of the strains were also
      consistent with their classification into this genus. The levels of 16S rRNA gene
      sequence similarity between strain PSD1-4T and other Chryseobacterium species
      were 95.2-97.2%; those between PHA3-4T and others were 93.7-97.8%. The DNA-DNA
      relatedness data indicated that strains PSD1-4T and PHA3-4T were clearly
      different from the nearest species, Chryseobacterium indoltheticum and
      Chryseobacterium taichungense. The major fatty acids were 13-methyltetradecanoic
      acid (iso-C15:0), 3-hydroxy-15-methylhexadecanoic acid (iso-C17:0 3-OH) and omega
      9-cis-15-methylhexadecenoic acid (iso-C17:1omega9c) for both strains. On the
      basis of polyphasic taxonomic analysis results, it is evident that each of these
      strains represents a novel species of Chryseobacterium, for which the names
      Chryseobacterium soldanellicola sp. nov. (type strain PSD1-4T=KCTC 12382T=NBRC
      100864T) and Chryseobacterium taeanense sp. nov. (type strain PHA3-4T=KCTC
      12381T=NBRC 100863T) are proposed.

PMID- 16449452
TI  - Catellicoccus marimammalium gen. nov., sp. nov., a novel Gram-positive, catalase
      negative, coccus-shaped bacterium from porpoise and grey seal.
AB  - Two strains of an unknown Gram-positive, catalase-negative, facultatively
      anaerobic, coccus-shaped bacterium, originating from a porpoise and a grey seal,
      were characterized using phenotypic, biochemical and molecular phylogenetic
      methods. Chemical studies revealed the presence of a cell-wall murein based on L
      lysine (type L-lys-gly-D-Asp) and a DNA G+C content of 38 mol%. Comparative 16S
      rRNA gene sequencing showed that this unidentified coccus-shaped organism formed
      a hitherto unknown subline closely related to, albeit distinct from, a number of
      other catalase-negative genera which included Enterococcus, Melissococcus,
      Tetragenococcus and Vagococcus. Other known Gram-positive, catalase-negative taxa
      were more distantly related. Tree-branching considerations and sequence
      divergence values of >6% with recognized taxa were indicative of this novel
      bacterium representing a separate genus. Based on phenotypic and phylogenetic
      evidence, it is proposed that this unknown bacterium, recovered from a porpoise
      and a grey seal, be classified as a novel genus and species, Catellicoccus
      marimammalium gen. nov., sp. nov. The type strain is M35/04/3T (=CCUG 49459T=CIP
      108575T).

PMID- 16449454
TI  - Flavobacterium saliperosum sp. nov., isolated from freshwater lake sediment.
AB  - An aerobic, yellow-pigmented, Gram-negative bacterium, designated strain S13T,
      was isolated from freshwater sediment of Taihu Lake in central China. The
      taxonomy of strain S13T was studied by using phenotypic and phylogenetic methods.
      Cells of strain S13T were rod-shaped, non-motile and with a size range of 0.35
      0.55x1.5-2.5 microm. The nearly complete 16S rRNA gene of strain S13T was
      amplified and sequenced. A blast search and phylogenetic analysis based on 16S
      rRNA gene sequence similarity showed that strain S13T was related to members of
      the genus Flavobacterium, with the highest sequence similarity of 93.8% to
      Flavobacterium columnare (ATCC 23463T). Cells contained menaquinone-6 (MK-6) as
      the major respiratory quinone and the genomic DNA G+C content was 41 mol%. The
      major fatty acids were iso-C15:0 (28.2%) and iso-C17:1omega9c (19.0%). It is
      proposed that S13T (=CGMCC 1.3801T=JCM 13331T) represents the type strain of a
      novel species, Flavobacterium saliperosum sp. nov.

PMID- 16449455
TI  - Shinella granuli gen. nov., sp. nov., and proposal of the reclassification of
      Zoogloea ramigera ATCC 19623 as Shinella zoogloeoides sp. nov.
AB  - The taxonomic position of a novel bacterial strain, Ch06T, isolated from an
      upflow anaerobic sludge blanket reactor was determined. Strain Ch06T was Gram
      negative, aerobic, motile and oxidase- and catalase-positive. A comparative 16S
      rRNA gene sequence analysis showed a clear affiliation of strain Ch06T to the
      Alphaproteobacteria and it was most closely related to Zoogloea ramigera ATCC
      19623 and Mycoplana dimorpha IAM 13154T (97.9 and 96.3% sequence similarity,
      respectively). The major respiratory quinone was Q-10 and the predominant fatty
      acids were C16:0, 3-OH C16:0, C18:0, C19:0 cyclo omega8c and summed feature 7
      (C18:1omega7c/omega9t/omega12t, C18:1omega7c/omega9c/omega12t). On the basis of
      phenotypic, chemotaxonomic and phylogenetic characteristics, the novel isolate
      was assigned to a new genus, Shinella gen. nov., as Shinella granuli gen. nov.,
      sp. nov. (type strain Ch06T=KCTC 12237T=JCM 13254T). It is proposed that Zoogloea
      ramigera ATCC 19623 is reclassified into the novel genus Shinella as Shinella
      zoogloeoides sp. nov. (type strain ATCC 19623T=IAM 12669T=I-16-MT).

PMID- 16449456
TI  - Lactobacillus rennini sp. nov., isolated from rennin and associated with cheese
      spoilage.
AB  - Two bacterial strains, DSM 20253T and DSM 20254, isolated from rennin and
      regarded as causing cheese spoilage, were deposited in the DSMZ as Lactobacillus
      sp. by J. Stadhouders. The strains show 99.9% 16S rRNA gene sequence similarity
      and have less than 94.3% similarity with any other species of the genus.
      Lactobacillus coryniformis is their closest phylogenetic neighbour. DNA-DNA
      hybridization experiments confirmed that the two strains are members of the same
      species with separate status within the genus Lactobacillus. The strains are
      homofermentative lactic acid bacteria and can be phenotypically and genotypically
      distinguished from their closest relatives. 16S rRNA gene-targeted specific
      primers were designed to enable PCR detection of the novel species. The name
      Lactobacillus rennini sp. nov. is proposed for the novel isolates, with strain
      CECT 5922T (=DSM 20253T) as the type strain.

PMID- 16449457
TI  - Burkholderia terrae sp. nov., isolated from a forest soil.
AB  - A Gram-negative, slightly curved rod-shaped bacterium, designated strain KMY02T,
      was isolated from a forest soil in Daejeon, South Korea. On the basis of 16S rRNA
      gene sequence similarity, strain KMY02T was shown to belong to the family
      Burkholderiaceae of the Betaproteobacteria, and to be related most closely to
      Burkholderia hospita LMG 20598T (98.7%), Burkholderia caribensis LMG 18531T
      (98.0%) and Burkholderia phymatum LMG 21445T (97.4%). Its phylogenetic distance
      from all recognized species within the genus Burkholderia was less than 97%.
      Chemotaxonomic data [Q-8 as the major ubiquinone; C16:0, C17:0 cyclo, summed
      feature 7 (C18:1omega7c/omega9t/omega12t) and C15:0 as the major fatty acids]
      supported the affiliation of strain KMY02T to the genus Burkholderia. The results
      of DNA-DNA hybridization experiments and physiological and biochemical tests
      allowed genotypic and phenotypic differentiation of the strain from recognized
      Burkholderia species. Therefore, KMY02T (=KCTC 12388T=NBRC 100964T) represents
      the type strain of a novel species, for which the name Burkholderia terrae sp.
      nov. is proposed.

PMID- 16449458
TI  - Massilia dura sp. nov., Massilia albidiflava sp. nov., Massilia plicata sp. nov.
      and Massilia lutea sp. nov., isolated from soils in China.
AB  - Four Gram-negative, motile, rod-shaped bacterial strains were isolated from soil
      samples collected from south-east China. A taxonomic study including phylogenetic
      analysis based on 16S rRNA gene sequences and phenotypic characteristics was
      performed. DNA G+C contents of the four strains were 63-66 mol%. Their
      predominant ubiquinone was Q-8. The fatty acid profiles contained C16:1omega7c
      (36.9-54.7%) and C16:0 (22.8-25.5%) as the major components. Based on their
      phenotypic characteristics, phylogenetic position as determined by 16S rRNA gene
      sequence analysis and DNA-DNA hybridization results, the four isolates are
      considered to represent four novel species of the genus Massilia, for which the
      names Massilia dura sp. nov. (type strain 16T=CCTCC AB 204070T=KCTC 12342T),
      Massilia albidiflava sp. nov. (type strain 45T=CCTCC AB 204071T=KCTC 12343T),
      Massilia plicata sp. nov. (type strain 76T=CCTCC AB 204072T=KCTC 12344T) and
      Massilia lutea sp. nov. (type strain 101T=CCTCC AB 204073T=KCTC 12345T) are
      proposed.

PMID- 16449459
TI  - Acaricomes phytoseiuli gen. nov., sp. nov., isolated from the predatory mite
      Phytoseiulus persimilis.
AB  - A Gram-positive, rod-shaped, non-spore-forming bacterium, strain CSCT, was
      isolated from diseased, surface-sterilized specimens of the predatory mite
      Phytoseiulus persimilis Athias-Henriot and subjected to polyphasic taxonomic
      analysis. Comparative analysis of the 16S rRNA gene sequence revealed that the
      strain was a new member of the family Micrococcaceae. Nearest phylogenetic
      neighbours were determined as Renibacterium salmoninarum (94.0%), Arthrobacter
      globiformis (94.8%) and Arthrobacter russicus (94.6%). Although the predominant
      fatty acids (anteiso C15:0), cell-wall sugars (galactose, glucose) and polar
      lipids (diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol) are
      in accordance with those of members of the genus Arthrobacter, strain CSCT can be
      distinguished from members of the genus Arthrobacter by biochemical tests, the
      absence of a rod-coccus life cycle and the occurrence of the partially saturated
      menaquinone MK-10(H2) as the predominant menaquinone. The DNA G+C content is 57.7
      mol%. On the basis of morphological, chemotaxonomic and phylogenetic differences
      from other species of the Micrococcaceae, a novel genus and species are proposed,
      Acaricomes phytoseiuli gen. nov., sp. nov. The type strain is CSCT (=DSM
      14247T=CCUG 49701T).

PMID- 16449460
TI  - Streptomyces cheonanensis sp. nov., a novel streptomycete with antifungal
      activity.
AB  - Actinomycete strain VC-A46T, which exhibits antifungal activity, was isolated
      from a soil sample collected from Cheonan, Korea. The strain was determined to
      belong to the genus Streptomyces, based on its morphological and chemotaxonomic
      characteristics. The cell wall of this strain contained ll-diaminopimelic acid.
      The predominant fatty acids were iso-C16:0, C16:0 and C16:1 cis 9. The DNA G+C
      content of strain VC-A46T was 75.5 mol%. Phylogenetic analysis of the 16S rRNA
      gene sequence of this strain revealed that it differed from those of the
      described streptomycetes available in public databases. Analyses of DNA-DNA
      relatedness data, together with data regarding the strain's morphological,
      physiological and biochemical characteristics, also confirmed that this strain
      constitutes a novel Streptomyces taxon, which is distinguishable from closely
      related reference strains. Therefore, it is proposed that strain VC-A46T (=KCCM
      42119T=NBRC 100940T) represents the type strain of a novel species, named
      Streptomyces cheonanensis sp. nov.

PMID- 16449461
TI  - Novel Neosartorya species isolated from soil in Korea.
AB  - Phenotypic and genotypic characters of strains of Neosartorya spinosa and related
      taxa were analysed. N. spinosa, Neosartorya botucatensis and Neosartorya
      paulistensis had identical partial beta-tubulin and calmodulin gene sequences and
      could not be differentiated on macro- and micro-morphological characteristics,
      including by scanning electron microscopy. Based on partial beta-tubulin and
      calmodulin gene sequences and ascospore morphology, two separate groups are
      distinguished and are proposed as novel species. Neosartorya laciniosa sp. nov.
      has microtuberculate ascospores with two bent crests and two distinct equatorial
      rings of small projections. Neosartorya coreana sp. nov. has rugose to weak
      reticulate ascospores with two often bent crests, but without the equatorial
      rings of small projections. The type strain of N. laciniosa is CBS 117721T (=NRRL
      35589T=KACC 41657T) and the type strain of N. coreana is CBS 117059T (=NRRL
      35590T=KACC 41659T).

PMID- 16449462
TI  - The status of the genus name Halovibrio Fendrich 1989 and the identity of the
      strains Pseudomonas halophila DSM 3050 and Halomonas variabilis DSM 3051. Request
      for an opinion.
AB  - During the course of studies on halophilic, Gram-negative bacteria, a comparison
      of two strains of halophilic bacteria, Pseudomonas halophila DSM 3050 and
      Halomonas variabilis DSM 3051 (formerly Halovibrio variabilis) demonstrated that
      the characteristics of strain DSM 3050 corresponded to the original description
      of Halovibrio variabilis and those of DSM 3051 to P. halophila, both of which had
      been isolated from the Great Salt Lake in Utah [Fendrich, C. (1988). Syst Appl
      Microbiol 11, 36-43]. It was concluded that these two strains did not correspond
      with their original descriptions, e.g. the original description of Halovibrio
      variabilis matched that of Pseudomonas halophila DSM 3050 and the original
      description of Pseudomonas halophila matched that of Halovibrio variabilis DSM
      3051, which was subsequently transferred to the genus Halomonas as Halomonas
      variabilis DSM 3051. These findings raise the question of whether the genus name
      Halovibrio, with the type species Halovibrio variabilis, should be associated
      with type strain DSM 3050 and recognition of strain DSM 3051 as the type strain
      of Pseudomonas halophila.

PMID- 16449463
TI  - Proposal that Agrobacterium radiobacter has priority over Agrobacterium
      tumefaciens. Request for an opinion.
AB  - It is proposed that Agrobacterium radiobacter has priority as the earlier
      heterotypic (subjective) synonym when it is united with Agrobacterium
      tumefaciens. The nomenclatural status of A. tumefaciens as a later heterotypic
      synonym of the united species is not lost and it remains the type species of the
      genus. Request for an opinion.

PMID- 16449464
TI  - Bipolar disorder treatment: an evidence-based reality check.

PMID- 16449465
TI  - What is bipolar disorder?

PMID- 16449466
TI  - Pathological gambling: focusing on the addiction, not the activity.

PMID- 16449467
TI  - Psychotherapy in the Journal: what's missing?

PMID- 16449469
TI  - Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine
      beats olanzapine: an exploratory analysis of head-to-head comparison studies of
      second-generation antipsychotics.
AB  - OBJECTIVE: In many parts of the world, second-generation antipsychotics have
      largely replaced typical antipsychotics as the treatment of choice for
      schizophrenia. Consequently, trials comparing two drugs of this class--so-called
      head-to-head studies--are gaining in relevance. The authors reviewed results of
      head-to-head studies of second-generation antipsychotics funded by pharmaceutical
      companies to determine if a relationship existed between the sponsor of the trial
      and the drug favored in the study's overall outcome. METHOD: The authors
      identified head-to-head comparison studies of second-generation antipsychotics
      through a MEDLINE search for the period from 1966 to September 2003 and
      identified additional head-to-head studies from selected conference proceedings
      for the period from 1999 to February 2004. The abstracts of all studies fully or
      partly funded by pharmaceutical companies were modified to mask the names and
      doses of the drugs used in the trial, and two physicians blinded to the study
      sponsor reviewed the abstracts and independently rated which drug was favored by
      the overall outcome measures. Two authors who were not blinded to the study
      sponsor reviewed the entire report of each study for sources of bias that could
      have affected the results in favor of the sponsor's drug. RESULTS: Of the 42
      reports identified by the authors, 33 were sponsored by a pharmaceutical company.
      In 90.0% of the studies, the reported overall outcome was in favor of the
      sponsor's drug. This pattern resulted in contradictory conclusions across studies
      when the findings of studies of the same drugs but with different sponsors were
      compared. Potential sources of bias occurred in the areas of doses and dose
      escalation, study entry criteria and study populations, statistics and methods,
      and reporting of results and wording of findings. CONCLUSIONS: Some sources of
      bias may limit the validity of head-to-head comparison studies of second
      generation antipsychotics. Because most of the sources of bias identified in this
      review were subtle rather than compelling, the clinical usefulness of future
      trials may benefit from minor modifications to help avoid bias. The authors make
      a number of concrete suggestions for ways in which potential sources of bias can
      be addressed by study initiators, peer reviewers of studies under consideration
      for publication, and readers of published studies.

PMID- 16449470
TI  - New-onset bipolar disorder in late life: a case of mistaken identity.

PMID- 16449471
TI  - Myocarditis during clozapine treatment.

PMID- 16449472
TI  - Victor Kandinsky, M.D., 1849-1889.

PMID- 16449473
TI  - Treatment-resistant bipolar depression: a STEP-BD equipoise randomized
      effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or
      risperidone.
AB  - OBJECTIVE: Clinicians have few evidence-based options for the management of
      treatment-resistant bipolar depression. This study represents the first
      randomized trial of competing options for treatment-resistant bipolar depression
      and assesses the effectiveness and safety of antidepressant augmentation with
      lamotrigine, inositol, and risperidone. METHOD: Participants (N=66) were patients
      with bipolar I or bipolar II disorder enrolled in the NIMH Systematic Treatment
      Enhancement Program for Bipolar Disorder (STEP-BD). All patients were in a
      current major depressive episode that was nonresponsive to a combination of
      adequate doses of established mood stabilizers plus at least one antidepressant.
      Patients were randomly assigned to open-label adjunctive treatment with
      lamotrigine, inositol, or risperidone for up to 16 weeks. The primary outcome
      measure was the rate of recovery, defined as no more than two symptoms meeting
      DSM-IV threshold criteria for a mood episode and no significant symptoms present
      for 8 weeks. RESULTS: No significant between-group differences were seen when any
      pair of treatments were compared on the primary outcome measure. However, the
      recovery rate with lamotrigine was 23.8%, whereas the recovery rates with
      inositol and risperidone were 17.4% and 4.6%, respectively. Patients receiving
      lamotrigine had lower depression ratings and Clinical Global Impression severity
      scores as well as greater Global Assessment of Functioning scores compared with
      those receiving inositol and risperidone. CONCLUSIONS: No differences were found
      in primary pairwise comparison analyses of open-label augmentation with
      lamotrigine, inositol, or risperidone. Post hoc secondary analyses suggest that
      lamotrigine may be superior to inositol and risperidone in improving treatment
      resistant bipolar depression.

PMID- 16449475
TI  - Clinical features of bipolar depression versus major depressive disorder in large
      multicenter trials.
AB  - OBJECTIVE: Failure to recognize bipolar disorder in patients who experience a
      major depressive episode may lead to inappropriate treatment and poorer outcomes.
      Clinical features that could distinguish bipolar from unipolar depression would
      facilitate more appropriate treatment selection. METHOD: The authors used data
      from nonpsychotic outpatients participating in three large multicenter clinical
      trials conducted in the United States for the treatment of major depressive
      episodes to compare 477 subjects with a diagnosis of bipolar disorder and 1,074
      with major depressive disorder. RESULTS: Bipolar depression was associated with
      family history of bipolar disorder, an earlier age at onset, a greater previous
      number of depressive episodes, and eight individual symptom items on the
      Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale.
      Fears were more common in patients with bipolar disorder, whereas sadness;
      insomnia; intellectual (cognitive), somatic (muscular), respiratory,
      genitourinary complaints; and depressed behavior were more common in patients
      with unipolar depression. A logistic regression model correctly classified 86.9%
      of the subjects. CONCLUSIONS: Bipolar depression and major depressive disorder
      exhibit subtle differences in presentation, which may help guide the initial
      diagnosis.

PMID- 16449474
TI  - Predictors of recurrence in bipolar disorder: primary outcomes from the
      Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).
AB  - OBJECTIVE: Little is known about clinical features associated with the risk of
      recurrence in patients with bipolar disorder receiving treatment according to
      contemporary practice guidelines. The authors looked for the features associated
      with risk of recurrence. METHOD: The authors examined prospective data from a
      cohort of patients with bipolar disorder participating in the multicenter
      Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for
      up to 24 months. For those who were symptomatic at study entry but subsequently
      achieved recovery, time to recurrence of mania, hypomania, mixed state, or a
      depressive episode was examined with Cox regression. RESULTS: Of 1,469
      participants symptomatic at study entry, 858 (58.4%) subsequently achieved
      recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals
      experienced recurrences, with more than twice as many developing depressive
      episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes
      (118, 13.8%). The time until 25% of the individuals experienced a depressive
      episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode
      was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion
      of days depressed or anxious in the preceding year were significantly associated
      with shorter time to depressive recurrence. Residual manic symptoms at recovery
      and proportion of days of elevated mood in the preceding year were significantly
      associated with shorter time to manic, hypomanic, or mixed episode recurrence.
      CONCLUSIONS: Recurrence was frequent and associated with the presence of residual
      mood symptoms at initial recovery. Targeting residual symptoms in maintenance
      treatment may represent an opportunity to reduce risk of recurrence.

PMID- 16449476
TI  - Risk of switch in mood polarity to hypomania or mania in patients with bipolar
      depression during acute and continuation trials of venlafaxine, sertraline, and
      bupropion as adjuncts to mood stabilizers.
AB  - OBJECTIVE: The authors examined the comparative risks of switches in mood
      polarity into hypomania or mania during acute and continuation trials of
      adjunctive antidepressant treatment of bipolar depression. METHOD: One hundred
      fifty-nine patients with bipolar I disorder or bipolar II disorder participated
      in a total of 228 acute (10-week) randomized trials of bupropion, sertraline, or
      venlafaxine as an adjunct to a mood stabilizer. Patients in 87 of these trials
      entered continuation treatment for up to 1 year. Antidepressant response and the
      occurrence of subthreshold brief hypomania (emergence of brief hypomania [at
      least 1 but <7 days] or recurrent brief hypomania) and threshold switches
      (emergence of full-duration hypomania [> or =7 days] or mania) were blindly
      assessed by using clinician-rated daily reports of mood-associated dysfunction on
      the National Institute of Mental Health Life Chart Method. RESULTS: Threshold
      switches into full-duration hypomania and mania occurred in 11.4% and 7.9%,
      respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively,
      of the continuation trials. The rate of threshold switches was higher in the 169
      trials in patients with bipolar I disorder (30.8%) than the 59 trials in patients
      with bipolar II disorder (18.6%). The ratio of threshold switches to subthreshold
      brief hypomanias was higher in both the acute (ratio=3.60) and continuation
      trials (ratio=3.75) of venlafaxine than in the acute and continuation trials of
      bupropion (ratios=0.85 and 1.17, respectively) and sertraline (ratios=1.67 and
      1.66, respectively). In only 37 (16.2%) of the original 228 acute antidepressant
      trials, or in only 23.3% of the patients, was there a sustained antidepressant
      response in the continuation phase in the absence of a threshold switch.
      CONCLUSIONS: Adjunctive treatment with antidepressants in bipolar depression was
      associated with substantial risks of threshold switches to full-duration
      hypomania or mania in both acute and long-term continuation treatment. Of the
      three antidepressants included in the study, venlafaxine was associated with the
      highest relative risk of such switching and bupropion with the lowest risk.

PMID- 16449477
TI  - Clinical correlates and familial aggregation of age at onset in bipolar disorder.
AB  - OBJECTIVE: To assess whether age at onset variation reflects underlying genetic
      heterogeneity in bipolar disorder, the authors examined the clinical and familial
      characteristics of age at onset in bipolar disorder subjects from families with
      multiple affected members. METHOD: A total of 211 families with 1,856 subjects
      were ascertained through bipolar I disorder probands. All the subjects were
      assessed with the Diagnostic Interview for Genetic Studies and assigned diagnoses
      by trained clinicians using best estimate procedures. Admixture analysis with the
      211 bipolar disorder probands was used to decompose the age-at-onset distribution
      into a mixture of theoretical normal distributions. Logistic regression with
      general estimating equations was then used to examine clinical correlates and
      familial aggregation of age at onset in all 717 bipolar disorder subjects.
      RESULTS: The age-at-onset distribution consisted of a mixture of three normal
      distributions with means of 16.6 (SD=5.1), 26.0 (SD=1.4), and 34.7 (SD=6.6) years
      that comprised 79.7%, 7.2%, and 13.1% of the group, respectively. Cutoff points
      at ages 21 and 28 were derived from this analysis and used to define age-at-onset
      subgroups. Early-onset (age at onset </=21) subjects had higher risks of drug
      abuse, alcohol abuse, rapid cycling, and suicide attempts. Affected subjects from
      a family with an early-onset proband were more likely than others to have an
      early onset (odds ratio=4.53, 95% CI=3.09-6.64). Subjects from a family with a
      proband whose age at onset was <28 were also more likely to have higher risks of
      drug abuse (odds ratio=11.62, 95% CI=2.16-62.66). CONCLUSIONS: Age at onset is
      associated with clinical heterogeneity in bipolar disorder and aggregates,
      possibly along with drug abuse, within families. These findings are consistent
      with the conclusion that age at onset reflects underlying genetic heterogeneity
      in bipolar disorder. Thus, age at onset may conceivably be used to identify more
      homogeneous groups of bipolar disorder families and thereby facilitate the
      mapping of bipolar disorder susceptibility genes.

PMID- 16449478
TI  - Randomized, placebo-controlled trial of olanzapine as maintenance therapy in
      patients with bipolar I disorder responding to acute treatment with olanzapine.
AB  - OBJECTIVE: In a placebo-controlled, double-blind study, the authors investigated
      the efficacy and safety of olanzapine as monotherapy in relapse prevention in
      bipolar I disorder. METHOD: Patients achieving symptomatic remission from a manic
      or mixed episode of bipolar I disorder (Young Mania Rating Scale [YMRS] total
      score < or =12 and 21-item Hamilton Depression Rating Scale [HAM-D] score <or =8)
      at two consecutive weekly visits following 6-12 weeks of open-label acute
      treatment with 5-20 mg/day of olanzapine were randomly assigned to double-blind
      maintenance treatment with olanzapine (N=225) or placebo (N=136) for up to 48
      weeks. The primary measure of efficacy was time to symptomatic relapse into any
      mood episode (YMRS score > or =15, HAM-D score > or =15, or hospitalization).
      RESULTS: Time to symptomatic relapse into any mood episode was significantly
      longer among patients receiving olanzapine (a median of 174 days, compared with a
      median of 22 days in patients receiving placebo). Times to symptomatic relapse
      into manic, depressive, and mixed episodes were all significantly longer among
      patients receiving olanzapine than among patients receiving placebo. The relapse
      rate was significantly lower in the olanzapine group (46.7%) than in the placebo
      group (80.1%). During olanzapine treatment, the most common emergent event was
      weight gain; during the open-label phase, patients who received olanzapine gained
      a mean of 3.1 kg (SD=3.4). In double-blind treatment, placebo patients lost a
      mean of 2.0 kg (SD=4.4) and patients who continued to take olanzapine gained an
      additional 1.0 kg (SD=5.2). CONCLUSIONS: Compared to placebo, olanzapine delays
      relapse into subsequent mood episodes in bipolar I disorder patients who
      responded to open-label acute treatment with olanzapine for a manic or mixed
      episode.

PMID- 16449480
TI  - Laboratory-observed behavioral disinhibition in the young offspring of parents
      with bipolar disorder: a high-risk pilot study.
AB  - OBJECTIVE: This study tested whether behavioral disinhibition is more prevalent
      among offspring of parents with bipolar disorder than among offspring of parents
      without bipolar disorder. METHOD: The authors conducted a secondary analysis of
      data from a preexisting high-risk study of offspring at risk for panic disorder
      and depression (N=278) that had included some children with parents who had
      bipolar disorder (N=34). Children (ages 2-6) had been classified as behaviorally
      inhibited, disinhibited, or neither in laboratory assessments. RESULTS: Offspring
      of bipolar parents had significantly higher rates of behavioral disinhibition
      than offspring of parents without bipolar disorder. Behavioral inhibition did not
      differ between groups. Differences were not accounted for by parental panic
      disorder or major depression or by parental history of attention deficit
      hyperactivity disorder, conduct disorder, antisocial personality, or substance
      use disorders. CONCLUSIONS: Results suggest a familial link between bipolar
      disorder in parents and behavioral disinhibition in their offspring. Behavioral
      disinhibition may be a familially transmitted predisposing factor for
      dysregulatory distress later in life.

PMID- 16449479
TI  - Risk and resilience markers in bipolar disorder: brain responses to emotional
      challenge in bipolar patients and their healthy siblings.
AB  - OBJECTIVE: The authors previously identified depression-specific differences in
      brain responses to an emotional challenge in patients with bipolar and unipolar
      mood disorder. In this study, potential markers of bipolar risk and resilience
      were examined in a new cohort of lithium-responsive bipolar patients and their
      healthy siblings. METHOD: Changes in regional cerebral blood flow (rCBF) were
      measured with [(15)O]water positron emission tomography after induction of
      transient sadness in nine euthymic lithium responders and nine healthy siblings.
      The patterns of change in these groups were compared, and then they were
      contrasted with previous findings on bipolar responders to valproate. RESULTS:
      Common to all three groups with induced sadness were rCBF increases in the
      dorsal/rostral anterior cingulate and anterior insula and decreases in the
      orbitofrontal and inferior temporal cortices. Distinguishing the groups were
      decreases in the medial frontal cortex in the patients but an increase in this
      region in the siblings. DISCUSSION: Common changes with emotional challenge were
      identified in bipolar patients and their healthy siblings. These were not seen
      previously in healthy subjects without a family history of mood disorder,
      suggesting a potential marker of bipolar risk. The siblings' unique increases in
      the medial frontal cortex appear to identify a compensatory response in this at
      risk group, as this pattern was not seen previously in healthy subjects without
      depression risk factors. This differential change pattern in patients and their
      siblings highlights the role of the anterior cingulate and medial frontal regions
      in mediating resiliency and vulnerability in bipolar disorder families.

PMID- 16449481
TI  - Linear relationship of valproate serum concentration to response and optimal
      serum levels for acute mania.
AB  - OBJECTIVE: Several studies have shown that achieving adequate serum valproate
      levels is critical to rapid stabilization of acute mania, but estimates of the
      target therapeutic level have been imprecise. A post hoc analysis of pooled
      intent-to-treat data from three randomized, placebo-controlled studies of
      divalproex treatment for acute mania was performed to test a hypothesized linear
      relationship between serum concentration and response and to determine optimal
      blood levels for treatment of acute mania. METHOD: Subjects (N=374) were
      stratified into seven groups (six valproate serum level ranges and placebo), and
      effect size was determined for each. Linearity of dose response was tested with
      both parametric and nonparametric techniques. ANOVA was used to compare the
      response at each serum level range with that of placebo as well as the lowest
      valproate level (< =55.0 microg/ml). The mean serum valproate level was then
      determined for all subjects with an effect size greater than or equal to the
      maximal effect derived from linear modeling. RESULTS: The fit of blood level and
      response to a linear model was good. Efficacy was significantly greater than
      placebo beginning at the 71.4-85.0 microg/ml range and for all higher valproate
      levels; the 94.1-107.0 and >107.0 microg/ml groups were superior to the lowest
      valproate serum level group. The effect size associated with highest serum levels
      (>94 microg/ml) was 1.06 (0.59 after placebo correction). Subjects obtaining this
      effect or greater (N=84) had a mean serum level of 87.5 microg/ml. Blood levels
      in the lowest effective range were 60% more effective than placebo and in the
      higher ranges were 120% more effective. Tolerability appeared similar for all
      groups. CONCLUSIONS: The results of this study suggest that there is a linear
      relationship between valproate serum concentration and response and that the
      target blood level of valproate for best response in acute mania is above 94
      microg/ml.

PMID- 16449482
TI  - Basal ganglia shape alterations in bipolar disorder.
AB  - OBJECTIVE: Shape differences in the caudate heads and putamen were compared
      between drug-naive and drug-treated patients with bipolar disorder and healthy
      comparison subjects by using spherical harmonic (SPHARM) techniques. On the basis
      of previous studies, the authors hypothesized that the drug-naive patients would
      exhibit shape differences of the caudate heads and putamen, especially on the
      right side, relative to the healthy comparison subjects, and that shape
      differences, relative to healthy comparison subjects, would differ between drug
      naive and drug-treated patients. METHOD: Brain magnetic resonance images were
      acquired from 49 bipolar disorder patients (21 drug-naive and 28 drug-treated
      patients) and 37 healthy comparison subjects. Volumetric measurements were
      obtained, and SPHARM descriptions were used to measure between-group radius
      differences in the surfaces of the caudate heads and putamen. RESULTS: Although
      no significant between-group volume differences were found in the striatal
      structures, significant shape differences in the anterior and ventral surfaces of
      the striatum were observed. Specifically, shape differences, more prominent for
      the right side, were found for drug-naive bipolar disorder patients, relative to
      the healthy comparison subjects, but not for drug-treated bipolar disorder
      subjects. CONCLUSIONS: The findings suggest that drug-naive bipolar disorder
      patients have shape differences of the striatum, relative to healthy comparison
      subjects, and that these differences may be modulated by treatment. The findings
      more generally demonstrate the sensitivity of the SPHARM analytic technique for
      detecting subtle anatomical shape differences in small brain regions in the
      absence of volume differences.

PMID- 16449483
TI  - Neurocognitive function in unmedicated manic and medicated euthymic pediatric
      bipolar patients.
AB  - OBJECTIVE: A systematic evaluation of neuropsychological functioning in
      individuals with pediatric bipolar disorder is necessary to clarify the types of
      cognitive deficits that are associated with acutely ill and euthymic phases of
      the disorder and the effects of medication on these deficits. METHOD: Unmedicated
      (N=28) and medicated (N=28) pediatric bipolar patients and healthy individuals
      (N=28) (mean age=11.74 years, SD=2.99) completed cognitive testing. Groups were
      matched on age, sex, race, parental socioeconomic status, general intelligence,
      and single-word reading ability. A computerized neurocognitive battery and
      standardized neuropsychological tests were administered to assess attention,
      executive function, working memory, verbal memory, visual memory, visuospatial
      perception, and motor skills. RESULTS: Subjects with pediatric bipolar disorder,
      regardless of medication and illness status, showed impairments in the domains of
      attention, executive functioning, working memory, and verbal learning compared to
      healthy individuals. Also, bipolar subjects with comorbid attention deficit
      hyperactivity disorder (ADHD) performed worse on tasks assessing attention and
      executive function than patients with bipolar disorder alone. CONCLUSIONS: The
      absence of differences in the deficits of neurocognitive profiles between acutely
      ill unmedicated patients and euthymic medicated patients suggests that these
      impairments are trait-like characteristics of pediatric bipolar disorder. The
      cognitive deficits found in individuals with pediatric bipolar disorder suggest
      significant involvement of frontal lobe systems supporting working memory and
      mesial temporal lobe systems supporting verbal memory, regardless of ADHD
      comorbidity.

PMID- 16449484
TI  - Autistic social impairment in the siblings of children with pervasive
      developmental disorders.
AB  - OBJECTIVE: Sibling recurrence risk in autism has been estimated to be
      approximately 10%. This study investigated subsyndromal autistic impairments
      among siblings of probands with pervasive developmental disorders. METHOD: The
      authors used the Social Responsiveness Scale to obtain quantitative assessments
      of autistic social impairment in three groups of proband-sibling pairs: 1)
      autistic children from multiple-incidence families and their closest in age
      nonautistic brothers (N=49 pairs); 2) children with any pervasive developmental
      disorder, including autism, and their closest-in-age brothers (N=100 pairs), and
      3) children with psychopathology unrelated to autism and their closest-in-age
      brothers (N=45 pairs). RESULTS: Sibling Social Responsiveness Scale scores were
      continuously distributed and substantially elevated for both the autistic and
      pervasive developmental disorder groups. Highest scores (i.e., greatest
      impairment) were seen among siblings of autistic probands from multiple-incidence
      families, followed by siblings of probands with any pervasive developmental
      disorder, then siblings of probands with psychopathology unrelated to autism.
      CONCLUSIONS: Taken together with previous findings, these results support the
      notion that genetic susceptibility factors responsible for common, subsyndromal
      social impairments may be related to the causes of categorically defined
      pervasive developmental disorders.

PMID- 16449485
TI  - Natural recovery and treatment-seeking in pathological gambling: results of two
      U.S. national surveys.
AB  - OBJECTIVE: Pathological gambling is described in DSM-IV as a chronic and
      persisting disorder, but recent community-based longitudinal studies that have
      highlighted the transitory nature of gambling-related problems have called into
      question whether this is an accurate characterization. This emerging evidence of
      high rates of recovery coupled with low rates of treatment-seeking for
      pathological gambling suggests that natural recovery might be common. The purpose
      of the present study was to document the rates of recovery, treatment-seeking,
      and natural recovery among individuals with DSM-IV pathological gambling disorder
      in two large and representative U.S. national surveys. METHOD: Prevalences of
      recovery, treatment-seeking, and natural recovery were estimated among
      individuals from the Gambling Impact and Behavior Study (N=2,417) and the
      National Epidemiologic Survey on Alcohol and Related Conditions (N=43,093) who
      reported a lifetime history of DSM-IV pathological gambling disorder (N=21 and
      N=185, respectively). RESULTS: Among individuals with a lifetime history of DSM
      IV pathological gambling, 36%-39% did not experience any gambling-related
      problems in the past year, even though only 7%-12% had ever sought either formal
      treatment or attended meetings of Gamblers Anonymous. About one-third of the
      individuals with pathological gambling disorder in these two nationally
      representative U.S. samples were characterized by natural recovery. CONCLUSIONS:
      Pathological gambling may not always follow a chronic and persisting course. A
      substantial portion of individuals with a history of pathological gambling
      eventually recover, most without formal treatment. The results of large
      epidemiological surveys of pathological gambling may eventually overturn the
      established wisdom about pathological gambling disorder.

PMID- 16449486
TI  - Multicenter investigation of the opioid antagonist nalmefene in the treatment of
      pathological gambling.
AB  - OBJECTIVE: Pathological gambling is a disabling disorder experienced by
      approximately 1%-2% of adults and for which there are few empirically validated
      treatments. The authors examined the efficacy and tolerability of the opioid
      antagonist nalmefene in the treatment of adults with pathological gambling.
      METHOD: A 16-week, randomized, dose-ranging, double-blind, placebo-controlled
      trial was conducted at 15 outpatient treatment centers across the United States
      between March 2002 and April 2003. Two hundred seven persons with DSM-IV
      pathological gambling were randomly assigned to receive nalmefene (25 mg/day, 50
      mg/day, or 100 mg/day) or placebo. Scores on the primary outcome measure (Yale
      Brown Obsessive Compulsive Scale Modified for Pathological Gambling) were
      analyzed by using a linear mixed-effects model. RESULTS: Estimated regression
      coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had
      significantly different scores on the Yale-Brown Obsessive Compulsive Scale
      Modified for Pathological Gambling, compared to the placebo group. A total of
      59.2% of the subjects who received 25 mg/day of nalmefene were rated as "much
      improved" or "very much improved" at the last evaluation, compared to 34.0% of
      those who received placebo. Adverse experiences included nausea, dizziness, and
      insomnia. CONCLUSIONS: Subjects who received nalmefene had a statistically
      significant reduction in severity of pathological gambling. Low-dose nalmefene
      (25 mg/day) appeared efficacious and was associated with few adverse events.
      Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects.

PMID- 16449487
TI  - Lower switch rate in depressed patients with bipolar II than bipolar I disorder
      treated adjunctively with second-generation antidepressants.
AB  - OBJECTIVES: The authors compared the switch rate into hypomania/mania in
      depressed patients treated with second-generation antidepressants who had either
      bipolar I or bipolar II disorder. METHOD: In a 10-week trial, 184 outpatients
      with bipolar depression (134 with bipolar I disorder, 48 with bipolar II
      disorder, two with bipolar disorder not otherwise specified) were treated with
      one of three antidepressants as an adjunct to mood stabilizers. The patients'
      switch rates were assessed. Switch was defined as a Young Mania Rating Scale
      (YMRS) score >13 or a Clinical Global Impression (CGI) mania score > or =3
      (mildly ill). RESULTS: Depressed subjects with bipolar II disorder had a
      significantly lower acute switch rate into hypomania/mania when either YMRS or
      CGI criteria were used to define switch. CONCLUSIONS: These data suggest that
      depressed patients with bipolar II disorder are less vulnerable than those with
      bipolar I disorder to switch into hypomania/mania when treated with an
      antidepressant adjunctive to a mood stabilizer.

PMID- 16449489
TI  - Comorbidity in bipolar disorder among the elderly: results from an
      epidemiological community sample.
AB  - OBJECTIVE: This study sought to determine psychiatric comorbidity among elderly
      individuals with bipolar disorder. METHOD: An epidemiological community survey
      identified 84 elderly (ages >/=65) respondents with bipolar disorder, 1,327
      younger adults with bipolar disorder, and 8,121 elderly respondents without
      bipolar disorder. RESULTS: Elderly respondents with bipolar disorder reported
      lifetime and 12-month rates of comorbid alcohol use disorders (38.1%, 38.1%,
      respectively), dysthymia (15.5%, 7.1%), generalized anxiety disorder (20.5%,
      9.5%), and panic disorder (19.0%, 11.9%) that were significantly higher than
      among elderly respondents without bipolar disorder. They had lower lifetime and
      12-month rates of alcohol use disorders and lower 12-month rates of dysthymia and
      panic disorder than younger adults with bipolar disorder. Elderly men with
      bipolar disorder reported a greater prevalence of alcoholism; women reported a
      greater prevalence of panic disorder. CONCLUSIONS: Comorbid axis I disorders,
      including panic disorder, are common among elderly individuals with bipolar
      disorder.

PMID- 16449488
TI  - Differences in brain chemistry in children and adolescents with attention deficit
      hyperactivity disorder with and without comorbid bipolar disorder: a proton
      magnetic resonance spectroscopy study.
AB  - OBJECTIVE: The authors' goal was to investigate phosphatidylinositol and
      glutamatergic metabolism in the anterior cingulate cortex of children and
      adolescents with attention deficit hyperactivity disorder (ADHD) alone, children
      with ADHD plus bipolar disorder, and children with no axis I diagnosis. METHOD:
      Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate
      cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and
      no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were
      healthy comparison subjects. RESULTS: Children with ADHD had a significantly
      higher ratio of glutamate plus glutamine to myo-inositol-containing compounds
      than children with ADHD plus bipolar disorder and healthy children. CONCLUSIONS:
      myo-Inositol-containing compounds may provide information on the action of
      antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and
      glutamine are measures of glutamatergic neurotransmission and thus may also
      reflect changes in serotonin and dopamine pathways.

PMID- 16449490
TI  - Evidence of white matter pathology in bipolar disorder adolescents experiencing
      their first episode of mania: a diffusion tensor imaging study.
AB  - OBJECTIVE: Previous diffusion tensor imaging findings have supported suggestions
      that bipolar disorder is characterized by subtle white matter changes. The
      chronic nature of the study population, however, has limited interpretation of
      these findings. In this study the authors utilized diffusion tensor imaging to
      study white matter tracts of adolescents in their first episode of mania to
      address whether abnormalities are present in early bipolar disorder. METHOD:
      Eleven medication-naive adolescents in their first episode of mania and 17
      healthy subjects underwent diffusion tensor imaging scans. Fractional anisotropy
      and trace apparent diffusion coefficients of prefrontal and posterior regions of
      interest were compared between groups. RESULTS: Bipolar adolescents showed
      significantly decreased fractional anisotropy only in superior-frontal white
      matter tracts. Trace apparent diffusion coefficients did not significantly differ
      in any regions examined. CONCLUSIONS: These findings suggest that prefrontal
      white matter abnormalities are present early in bipolar disorder and may consist
      largely of axonal disorganization. The presence of changes in young first-episode
      patients also suggests that white matter pathology may represent an early marker
      of bipolar disorder.

PMID- 16449491
TI  - Pisa syndrome in a patient in a wheelchair taking valproic acid.

PMID- 16449492
TI  - QTc prolongation and torsades de pointes in an elderly woman taking fluoxetine.

PMID- 16449493
TI  - Comorbidity of anxiety with eating disorders and OCD.

PMID- 16449494
TI  - Comorbidity of anxiety with eating disorders and OCD.

PMID- 16449496
TI  - New mnemonic for depressive symptoms.

PMID- 16449495
TI  - Comorbidity of anxiety with eating disorders and OCD.

PMID- 16449498
TI  - Suicide risk in placebo-controlled trials of bipolar disorder.

PMID- 16449500
TI  - A systematic model to predict transcriptional regulatory mechanisms based on
      overrepresentation of transcription factor binding profiles.
AB  - An important aspect of understanding a biological pathway is to delineate the
      transcriptional regulatory mechanisms of the genes involved. Two important tasks
      are often encountered when studying transcription regulation, i.e., (1) the
      identification of common transcriptional regulators of a set of coexpressed
      genes; (2) the identification of genes that are regulated by one or several
      transcription factors. In this study, a systematic and statistical approach was
      taken to accomplish these tasks by establishing an integrated model considering
      all of the promoters and characterized transcription factors (TFs) in the genome.
      A promoter analysis pipeline (PAP) was developed to implement this approach. PAP
      was tested using coregulated gene clusters collected from the literature. In most
      test cases, PAP identified the transcription regulators of the input genes
      accurately. When compared with chromatin immunoprecipitation experiment data,
      PAP's predictions are consistent with the experimental observations. When PAP was
      used to analyze one published expression-profiling data set and two novel
      coregulated gene sets, PAP was able to generate biologically meaningful
      hypotheses. Therefore, by taking a systematic approach of considering all
      promoters and characterized TFs in our model, we were able to make more reliable
      predictions about the regulation of gene expression in mammalian organisms.

PMID- 16449501
TI  - Identification and analysis of evolutionarily cohesive functional modules in
      protein networks.
AB  - The increasing number of sequenced genomes makes it possible to infer the
      evolutionary history of functional modules, i.e., groups of proteins that
      contribute jointly to the same cellular function in a given species. Here we
      identify and analyze those prokaryotic functional modules, whose composition
      remains largely unchanged during evolution, and study their properties. Such
      "cohesive" modules have a large number of internal functional connections, encode
      genes that tend to be in close proximity in prokaryotic genomes, and correspond
      to physical complexes or complex functional systems like the flagellar apparatus.
      Cohesive modules are enriched in processes such as energy and amino acid
      metabolism, cell motility, and intracellular trafficking, or secretion. By
      grouping genes into modules we achieve a more precise estimate of their age and
      find that the young modules are often horizontally transferred between species
      and are enriched in functions involved in interactions with the environment,
      implying that they play an important role in the adaptation of species to new
      environments.

PMID- 16449502
TI  - High-throughput DNA methylation profiling using universal bead arrays.
AB  - We have developed a high-throughput method for analyzing the methylation status
      of hundreds of preselected genes simultaneously and have applied it to the
      discovery of methylation signatures that distinguish normal from cancer tissue
      samples. Through an adaptation of the GoldenGate genotyping assay implemented on
      a BeadArray platform, the methylation state of 1536 specific CpG sites in 371
      genes (one to nine CpG sites per gene) was measured in a single reaction by
      multiplexed genotyping of 200 ng of bisulfite-treated genomic DNA. The assay was
      used to obtain a quantitative measure of the methylation level at each CpG site.
      After validating the assay in cell lines and normal tissues, we analyzed a panel
      of lung cancer biopsy samples (N = 22) and identified a panel of methylation
      markers that distinguished lung adenocarcinomas from normal lung tissues with
      high specificity. These markers were validated in a second sample set (N = 24).
      These results demonstrate the effectiveness of the method for reliably profiling
      many CpG sites in parallel for the discovery of informative methylation markers.
      The technology should prove useful for DNA methylation analyses in large
      populations, with potential application to the classification and diagnosis of a
      broad range of cancers and other diseases.

PMID- 16449503
TI  - Pregnancy and delivery in women after Fontan palliation.
AB  - OBJECTIVES: To evaluate the outcome of pregnancy in women after Fontan palliation
      and to assess the occurrence of infertility and menstrual cycle disorders. DESIGN
      AND PATIENTS: Two congenital heart disease registries were used to investigate 38
      female patients who had undergone Fontan palliation (aged 18-45 years):
      atriopulmonary anastomosis (n = 23), atrioventricular connection (n = 5) and
      total cavopulmonary connection (n = 10). RESULTS: Six women had 10 pregnancies,
      including five miscarriages (50%) and one aborted ectopic pregnancy. During the
      remaining four live-birth pregnancies clinically significant complications were
      encountered: New York Heart Association class deterioration; atrial fibrillation;
      gestational hypertension; premature rupture of membranes; premature delivery;
      fetal growth retardation and neonatal death. Four of seven women who had
      attempted to become pregnant reported female infertility: non-specified secondary
      infertility (n = 2), uterus bicornis (n = 1) and related to endometriosis (n =
      1). Moreover, several important menstrual cycle disorders were documented. In
      particular, the incidence of primary amenorrhoea was high (n = 15, 40%), which
      resulted in a significant increase in age at menarche (14.6 (SD 2.1) years, p <
      0.0001, compared with the general population). CONCLUSION: Women can successfully
      complete pregnancy after adequate Fontan palliation without important long-term
      sequelae, although it is often complicated by clinically significant (non
      )cardiac events. In addition, subfertility or infertility and menstrual disorders
      were common.

PMID- 16449504
TI  - Atrioventricular block after transcatheter closure of perimembranous ventricular
      septal defects.
AB  - OBJECTIVE: To look at the presentation, treatment and outcome of patients who
      developed atrioventricular block after transcatheter closure of a perimembranous
      ventricular septal defect (PMVSD) with the Amplatzer PMVSD device. SETTING: Three
      tertiary referral centres for paediatric cardiology in two countries. RESULTS:
      All three patients presented within 10 days of the procedure. All three patients
      were treated with intravenous steroids. A permanent pacemaker was inserted in all
      patients but no pacemaker required activation after two months. CONCLUSION:
      Complete atrioventricular block occurring in the weeks after device occlusion of
      a PMVSD appears to resolve quickly. Continued involvement in multicentre device
      databases is required to monitor safety.

PMID- 16449505
TI  - Is there a place for D-dimers in acute type A aortic dissection?
AB  - Plasma concentrations of D-dimer may prove a valuable addition in the diagnostic
      work-up of acute type A aortic dissection, but not as means of predicting
      mortality.

PMID- 16449506
TI  - Darwin and the survival of the fittest in modern interventional cardiology.
AB  - The diabetic patient requires a full armamentarium of proven and developing
      treatments in order to minimise periprocedural risk as well as improve long term
      outcome.

PMID- 16449507
TI  - Tissue Doppler-derived index of left ventricular filling pressure, E/E', predicts
      survival of patients with non-valvular atrial fibrillation.
AB  - OBJECTIVES: To investigate whether the ratio of early transmitral flow velocity
      (E) to early diastolic mitral annular velocity (E') predict prognosis in patients
      with non-valvular atrial fibrillation. METHODS: 230 patients with non-valvular
      atrial fibrillation were enrolled and studied. According to E/E' value, patients
      were divided into groups with lower (group A with E/E' <or= 15) and higher (group
      B with E/E' > 15) E/E'. RESULTS: During follow up (average 245 days), 21 (9.1%)
      deaths were documented. All cause death (15/90 (16.7%) v 6/140 (4.3%)), cardiac
      death (10 (11.1%) v 2 (1.4%)) and congestive heart failure (16 (17.8%) v 8
      (5.7%)) were more common in group B than in group A (all p < 0.01). A Kaplan
      Meier survival curve showed that the cumulative survival rate was significantly
      lower in group B than in group A (log rank p = 0.0013). By multivariate logistic
      regression analysis, E/E' (chi(2) = 4.47, odds ratio (OR) 1.05, 95% confidence
      interval (CI) 1.01 to 1.11, p = 0.03) and age (chi(2) = 6.45, OR 1.06, 95% CI
      1.01 to 1.11, p = 0.02) were independent predictors of mortality. CONCLUSION: The
      Doppler-derived index of left ventricular filling pressure, E/E', is a powerful
      predictor of the clinical outcome of patients with non-valvular atrial
      fibrillation.

PMID- 16449508
TI  - Role of drug eluting stents in diabetic patients.
AB  - There is a clear need for a large multicentre trial comparing the efficacy of the
      two available drug eluting stents, sirolimus and paclitaxel, in diabetic patients
      with multivessel disease.

PMID- 16449509
TI  - Role of regional mechanical dyssynchrony as a determinant of functional mitral
      regurgitation in patients with left ventricular systolic dysfunction.
AB  - OBJECTIVE: To assess regional mechanical dyssynchrony as a determinant of the
      degree of functional mitral regurgitation (FMR). SETTING: Tertiary cardiology
      clinic. PATIENTS: 74 consecutive patients with left ventricular (LV) dysfunction
      (ejection fraction < 40%, mean 32.2 (SD 7.3)%) were evaluated. METHODS: Effective
      regurgitant orifice (ERO) area, indices of mitral deformation (systolic valvular
      tenting, mitral annular contraction) and of global LV function and remodelling
      (ejection fraction, end systolic volume, sphericity index) and local remodelling
      (papillary-fibrosa distance, regional wall motion score index), and tissue
      Doppler-derived dyssynchrony index (DI) (regional DI, defined as the standard
      deviation of time to peak myocardial systolic contraction of eight LV segments
      supporting the papillary muscles attachment) were measured. RESULTS: All the
      assessed variables correlated significantly with ERO. By multivariate analysis,
      systolic valvular tenting was the strongest independent predictor of ERO (R(2) =
      0.77, p = 0.0001), with a minor influence of papillary-fibrosa distance (R(2) =
      0.77, p = 0.01) and regional DI (R(2) = 0.77, p = 0.03). Local LV remodelling
      (regional wall motion score index: R(2) = 0.58, p = 0.001; papillary-fibrosa
      distance: R(2) = 0.58, p = 0.002) and global remodelling indices (sphericity
      index: R(2) = 0.58, p = 0.003) were the main determinants of systolic valvular
      tenting, whereas regional DI did not enter into the model. Regional DI was an
      independent predictor of ERO (R(2) = 0.56, p = 0.005) in patients with non
      ischaemic LV dysfunction but not in patients with ischaemic LV dysfunction when
      these groups were analysed separately. CONCLUSIONS: The degree of FMR is
      associated mainly with mitral deformation indices. The regional dyssynchrony also
      has an independent association with ERO but with a minor influence; however, it
      is not a determinant of FMR in patients with ischaemic LV dysfunction.

PMID- 16449510
TI  - Directional atherectomy facilitates the interventional procedure and leads to a
      low rate of recurrent stenosis in left anterior descending and left circumflex
      artery ostium stenoses: subgroup analysis of the FLEXI-CUT study.
AB  - OBJECTIVES: To examine by retrospective analysis of data from the FLEXI-CUT
      monocentre registry whether atherectomy can effectively simplify complex stent
      implantation in ostial bifurcation lesions by reducing the procedure to stenting
      of the left anterior descending (LAD) or left circumflex (LCX) artery ostium
      alone. PATIENTS AND METHODS: All patients who had been enrolled in the
      prospective FLEXI-CUT study (directional atherectomy with adjunctive balloon
      angioplasty) were retrospectively analysed on the basis of significant LAD or LCX
      ostial stenosis (>or= 70% stenosis) deriving from an undiseased left main stem.
      The primary combined end point was the rate of target lesion revascularisation
      (TLR) and binary restenosis; secondary end points were procedural success and
      major adverse cardiac events (MACE) at the six-month follow up. RESULTS: Of 30
      patients enrolled with significant LAD or LCX ostium stenosis, 29 were
      effectively treated with directional atherectomy (96.7% procedural success). All
      patients underwent single-vessel stenting procedures of solely the LAD or LCX
      ostium. At follow up, binary stenosis was 25% (6 of 24), TLR (angiographic plus
      clinical) 10.3% (3 of 29) and total MACE 6.9% (2 of 29). CONCLUSIONS: Directional
      atherectomy with single-vessel stenting procedures facilitates the interventional
      treatment of LAD and LCX ostium stenosis, and leads to remarkably low TLR and
      binary stenosis at follow up.

PMID- 16449511
TI  - Progressive coronary calcification despite intensive lipid-lowering treatment: a
      randomised controlled trial.
AB  - OBJECTIVES: To evaluate the effect of intensive lipid-lowering treatment on
      coronary artery calcification in a substudy of a trial recruiting patients with
      calcific aortic stenosis. METHODS: In a double blind randomised controlled trial,
      102 patients with calcific aortic stenosis and coronary artery calcification were
      randomly assigned by the minimisation technique to atorvastatin 80 mg daily or
      matched placebo. Coronary artery calcification was assessed annually by helical
      computed tomography. RESULTS: 48 patients were randomly assigned to atorvastatin
      and 54 to placebo with a median follow up of 24 months (interquartile range 24
      30). Baseline characteristics and coronary artery calcium scores were similar in
      both groups. Atorvastatin reduced serum low density lipoprotein cholesterol (
      53%, p < 0.001) and C reactive protein (-49%, p < 0.001) concentrations whereas
      there was no change with placebo (-7% and 17%, p > 0.95 for both). The rate of
      change in coronary artery calcification was 26%/year (0.234 (SE 0.037) log
      arbitrary units (AU)/year; n = 39) in the atorvastatin group and 18%/year (0.167
      (SE 0.034) log AU/year; n = 49) in the placebo group, with a geometric mean
      difference of 7%/year (95% confidence interval -3% to 18%, p = 0.18). Serum low
      density lipoprotein concentrations were not correlated with the rate of
      progression of coronary calcification (r = 0.05, p = 0.62). CONCLUSION: In
      contrast to previous observational studies, this randomised controlled trial has
      shown that, despite reducing systemic inflammation and halving serum low density
      lipoprotein cholesterol concentrations, statin treatment does not have a major
      effect on the rate of progression of coronary artery calcification.

PMID- 16449512
TI  - Outcome of acute fulminant myocarditis in children.
AB  - OBJECTIVES: To highlight clinical features and outcome of acute fulminant
      myocarditis (AFM) in children. METHODS: Diagnostic criteria were (1) the presence
      of severe and acute heart failure; (2) left ventricular dysfunction on
      echocardiography; (3) recent history of viral illness; and (4) no history of
      cardiomyopathy. RESULTS: Eleven children were included between 1998 and 2003, at
      a median age of 1 (0 to 9) year. Their mean left ventricular ejection fraction
      (LVEF) was 22 (SD 9)% at presentation. A virus was identified in five patients:
      human parvovirus B19 (n = 2), Epstein-Barr (n = 1), varicella zoster (n = 1), and
      coxsackie (n = 1). The median intensive care unit course was 13 (2-34) days.
      Intravenous inotropic support was required by nine patients and eight were
      mechanically ventilated. All patients received corticosteroid, associated with
      intravenous immunoglobulin in seven. Five patients experienced cardiocirculatory
      arrest that was successfully resuscitated in four. At a median follow up of 58.7
      (33.8-83.1) months, the 10 survivors are asymptomatic with normalised LVEF.
      CONCLUSION: Despite a severe presentation, the outcome of AFM is favourable.
      Aggressive symptomatic management is warranted and heart transplantation should
      be considered only when maximal supportive therapy does not lead to improvement.

PMID- 16449513
TI  - Non-invasive coronary flow reserve is correlated with microvascular integrity and
      myocardial viability after primary angioplasty in acute myocardial infarction.
AB  - OBJECTIVE: To test whether preserved coronary flow reserve (CFR) two days after
      reperfused acute myocardial infarction (AMI) is associated with less
      microvascular dysfunction (" no-reflow" phenomenon) and is predictive of
      myocardial viability. DESIGN: 24 patients with anterior AMI underwent CFR
      assessment in the left anterior descending coronary artery (LAD) with
      transthoracic echocardiography and myocardial contrast echocardiography (MCE) 48
      h after primary angioplasty in the LAD (mean 4 (SD 2) and 3 (1) days,
      respectively). Low-dose dobutamine echocardiography was performed 6 (3) days
      after AMI and follow-up echocardiography at three months. RESULTS: No-reflow
      extent was greater in patients with impaired CFR (< 2.5) than in those with
      preserved CFR (> 2.5) (55 (35)% v 11 (25)%, p < 0.001). MCE reflow was more
      common in patients with preserved CFR (8/12) than in those with reduced CFR
      (1/12, p < 0.05). Wall motion score index in the LAD territory (A-WMSI) was
      similar at the first echocardiography (2.14 (0.39) v 2.32 (0.47), NS), although
      it was better in patients with preserved CFR at dobutamine (1.38 (0.45) v 1.97
      (0.67), p < 0.05) and follow-up echocardiography (1.36 (0.40) v 1.97 (0.64), p <
      0.05). An inverse correlation was found between CFR and A-WMSI at dobutamine and
      follow-up echocardiography (r = -0.49, p = 0.016 and r = -0.55, p = 0.005) and
      between MCE and A-WMSI at dobutamine and follow-up echocardiography (r = -0.75, p
      < 0.001 and r = -0.75, p < 0.001). By multivariate analysis MCE reflow remained
      the only predictor of recovery at both dobutamine and follow-up echocardiography
      (odds ratio 1.06, 95% CI 1 to 1.1, p = 0.009). CONCLUSION: CFR is inversely
      correlated with the extent of microvascular dysfunction at MCE two days after
      reperfused AMI. CFR and MCE reflow early after AMI are correlated with myocardial
      viability at follow up.

PMID- 16449514
TI  - Delayed diagnosis of congenital heart disease worsens preoperative condition and
      outcome of surgery in neonates.
AB  - OBJECTIVES: To assess whether the route by which neonatal congenital heart
      disease (CHD) is first recognised influences outcome after surgery. METHODS:
      Surgical neonates admitted to a tertiary cardiac unit between March 1999 and
      February 2002 were retrospectively reviewed with analysis of risk factors for
      outcome. Three routes to initial recognition of CHD were compared: antenatal
      diagnosis, detection on the postnatal ward, and presentation after discharge to
      home. Outcome measures were mortality and duration of perioperative ventilation.
      RESULTS: 286 neonates had cardiac surgery with a median duration of ventilation
      of 101 h and in-hospital mortality of 12%. Recognition of CHD was antenatal in
      20%, on the postnatal ward in 55% and after discharge to home in 25%. Multiple
      regression analyses, including the cardiac diagnosis, associated problems and
      other risk factors, indicated that severe cardiovascular compromise on admission
      to the cardiac unit was significantly related to mortality and prolonged
      ventilation. Considered in isolation, the route to recognition of heart disease
      did not influence mortality or ventilation time. Route to initial recognition
      did, however, influence the patient's condition on admission to the cardiac unit.
      Cardiovascular compromise and end organ dysfunction were least likely when
      recognition was antenatal and most common when presentation followed discharge to
      home. CONCLUSION: The setting in which neonatal CHD is first recognised has an
      impact on preoperative condition, which in turn influences postoperative progress
      and survival after surgery. Optimal screening procedures and access to specialist
      care will improve outcome for neonates undergoing cardiac surgery.

PMID- 16449515
TI  - Increased frequency of cardioembolism and patent foramen ovale in patients with
      stroke and a positive travel history suggesting economy class stroke syndrome.
AB  - OBJECTIVE: To investigate the frequency of acute stroke in patients with a recent
      travel history and to analyse risk factors, stroke patterns and presence of a
      patent foramen ovale (PFO) in this patient group. DESIGN: One-year prospective
      observational study. SETTING: Single-centre study. METHODS: Enrolling all
      patients presenting with a first cerebral ischaemia and complementing the usual
      history with a standardised travel history. RESULTS: Of 338 patients with acute
      stroke, 42 had a positive travel history (PTH) (12.4%). Patients with a PTH were
      significantly younger (56.6 (SD 13) years) than patients (66.9 (13.2) years, p =
      0.0001) with a negative travel history (NTH). Frequency of PFO in the PTH group
      (13; 44.8%) was significantly higher than in the NTH group (7; 10.8%) (p =
      0.0001), even after patients were dichotomised into two age groups (younger and
      older than median of all PATIENTS: 31% v 6.1%, p = 0.007 and 13.8% v 4.6%, p =
      0.022, respectively). PTH patients had fewer stroke risk factors (2.2 (1.4) v 3.3
      (1.6), p = 0.0001) and a different risk profile with a lower frequency of
      diabetes (11.9% v 31.4%, p = 0.009), hypertension (52.4% v 78.7%, p = 0.0001),
      atrial fibrillation (7.1% v 22%, p = 0.025) and others (16.7% v 38.9%, p =
      0.005). In contrast, PTH patients had significantly more cardioembolic (35.7% v
      19.3%, p = 0.023) and cryptogenic strokes (50% v 19.9%, p = 0.0001) and more
      often ischaemia in the territory of the posterior cerebral artery (29.6% v 6.3%,
      p = 0.0001). CONCLUSIONS: The finding that more PTH patients had a PFO and a
      cardioembolic stroke pattern but that fewer had other typical stroke risk factors
      led to the hypothesis that PFO is a risk factor for economy class stroke
      syndrome.

PMID- 16449516
TI  - Multiple predictors of coronary restenosis after drug-eluting stent implantation
      in patients with diabetes.
AB  - OBJECTIVES: To identify parameters influencing the likelihood of restenosis after
      implantation of drug-eluting stents (DES) in patients with diabetes. METHODS:
      Stented patients (n = 840) with DES were retrospectively reviewed for inclusion
      in the study from the Multicenter PCI Database Registry. From this database, 211
      (25.1%) of 840 patients with six-month angiographic follow up had diabetes.
      Predictors of coronary restenosis were identified with univariate and
      multivariate logistic regression analyses. RESULTS: Restenosis occurred in 92 of
      629 (14.6%) patients without diabetes and in 44 (20.9%) of 211 patients with
      diabetes (p < 0.001). Multivariate parameters for predicting restenosis in the
      diabetic group were current smoking (odds ratio (OR) 1.923, 95% confidence
      interval (CI) 1.055 to 4.725, p = 0.036), higher C reactive protein concentration
      (OR 1.031, 95% CI 1.011 to 1.075, p = 0.043), use of the paclitaxel-eluting stent
      (OR 2.638, 95% CI 1.338 to 5.200, p = 0.005), longer stent length (OR 1.065, 95%
      CI 1.021 to 1.119, p = 0.033), smaller reference diameter before DES implantation
      (OR 0.501, 95% CI 0.110 to 0.965, p = 0.040), smaller reference diameter (OR
      0.455, 95% CI 0.120 to 0.814, p = 0.026) and minimum lumen diameter (OR 0.447,
      95% CI 0.068 to 0.876, p = 0.039) after DES implantation. CONCLUSION: Even with
      the introduction of DES, diabetes remains a significant predictor of coronary
      restenosis, especially in cases of a small baseline vessel size, small vessel
      size after percutaneous coronary intervention, longer stent length, use of the
      paclitaxel-eluting stent, current smoking and high C reactive protein
      concentration.

PMID- 16449517
TI  - Expression of bone-regulatory proteins in human valve allografts.
AB  - OBJECTIVE: To test the hypothesis that valve allograft (VA) calcification results
      from an ossification process in which bone-regulatory proteins are expressed.
      METHODS: 15 VA that were explanted at the time of surgery for dysfunction were
      studied. VA were analysed and compared with normal aortic valves (n = 20).
      RESULTS: All the VA (5 aortic, 10 pulmonary) exhibited heavy calcification and
      important fibrosis. Immunohistochemistry studies showed that the bone-specific
      transcription factor Cbfa-1 was expressed by stromal cells. Bone alkaline
      phosphatase was expressed in calcified regions. Immunostaining for alpha smooth
      muscle (alpha-SM) actin was increased in VA compared with normal valves and in 6
      of the 15 valves formed cellular clusters close to the calcified nodules. In VA
      osteopontin and osteonectin were expressed by stromal cells, whereas osteocalcin
      was closely associated with the calcified regions. Furthermore, analysis of the
      bone-regulatory proteins that control bone resorption showed that receptor
      activator of nuclear factor kappaB ligand (RANKL), receptor activator of nuclear
      factor kappaB (RANK) and osteoprotegerin (OPG) were differentially expressed in
      calcified VA and normal valves. Normal valve leaflets expressed OPG, whereas OPG
      expression was absent or faint in calcified VA. RANKL and RANK were not detected
      in normal valves, whereas calcified VA expressed RANKL and RANK. CONCLUSION:
      These data suggest that calcification of VA results from an ossification process,
      which relies on tight control of bone-regulatory protein expression. The
      expression pattern of the RANKL/RANK/OPG system suggests that it may have a
      regulatory role not only in osteoclastogenesis but also in the calcification of
      human VA.

PMID- 16449519
TI  - Head-to-head comparison of indices of left ventricular contractile reserve
      assessed by high-dose dobutamine stress echocardiography in idiopathic dilated
      cardiomyopathy: five-year follow up.
AB  - OBJECTIVE: To compare head to head the indices of left ventricular contractile
      reserve assessed by high-dose dobutamine in the five-year prognosis of patients
      with idiopathic dilated cardiomyopathy. DESIGN AND SETTING: Prospective study in
      a tertiary care centre. PATIENTS: 63 consecutive patients with idiopathic dilated
      cardiomyopathy. INTERVENTIONS: High-dose dobutamine stress echocardiography was
      performed in progressive stages lasting 5 min each. Wall motion score index,
      ejection fraction, cardiac power output and end systolic pressure to volume ratio
      were evaluated as indices of left ventricular contractility. MAIN OUTCOME
      MEASURE: Five-year cardiac mortality. RESULTS: During the follow up of 59
      patients, 27 (45.8%) died of cardiac causes. According to Kaplan-Meier and
      receiver operating characteristic analyses all indices of contractile reserve
      differentiated patients with respect to cardiac death. Wall motion score index
      achieved the best separation (log rank 21.75, p < 0.0001, area under the curve
      0.84), followed by change in ejection fraction (log rank 11.25, p = 0.0008, area
      under the curve 0.79), end systolic pressure to volume ratio (log rank 14.32, p =
      0.0002, area under the curve 0.75) and cardiac power output (log rank 9.84, p =
      0.0017, area under the curve 0.71). Cox's regression model identified wall motion
      score index as the only independent predictor of cardiac death. CONCLUSIONS:
      These data show that all examined indices of left ventricular contractile reserve
      are predictive of five-year prognosis, but change in wall motion score index may
      have the greatest prognostic potential.

PMID- 16449518
TI  - Prospective, randomised, controlled trial to study the effect of intracoronary
      injection of verapamil and adenosine on coronary blood flow during percutaneous
      coronary intervention in patients with acute coronary syndromes.
AB  - OBJECTIVES: To study the impact of injection of verapamil and adenosine in the
      coronary arteries on TIMI (Thrombolysis in Myocardial Infarction) frame count
      (TFC) after percutaneous coronary intervention (PCI) in patients with an acute
      coronary syndrome (ACS). METHODS: Prospective, randomised, controlled study of
      the intracoronary administration of normal saline versus verapamil versus
      adenosine in patients undergoing PCI in the setting of an ACS, even when flow is
      visually established to be normal or near normal. Patients were randomised to
      receive verapamil (n = 49), adenosine (n = 51) or normal saline (n = 50) after
      PCI. Quantitative angiography, TIMI flow grade (TFG), TFC and myocardial blush
      grade were assessed before PCI, after PCI and after drugs were given. Wall motion
      index (WMI) was measured at days 1 and 30. RESULTS: 9 patients in the verapamil
      group developed transient heart block, not seen with adenosine (p <or= 0.001).
      Compared with saline, coronary flow measured by TFC improved significantly and
      WMI improved slightly but insignificantly in both the verapamil (TFC: p = 0.02;
      mean difference in improvement in WMI: 0.09, 95% confidence interval (CI) 0.015
      to 0.17, p = 0.02) and the adenosine groups (TFC: p = 0.002; mean difference in
      improvement in WMI: 0.08, 95% CI 0.004 to 0.16, p = 0.04). The improvements in
      TFC and WMI did not differ significantly between the verapamil and the adenosine
      groups (TFC: p = 0.2; mean difference in improvement in WMI: 0.01, 95% CI -0.055
      to 0.08, p = 0.7, respectively). CONCLUSION: Administration of verapamil or
      adenosine significantly improves coronary flow and WMI after PCI in the setting
      of an ACS. Flow and WMI did not differ significantly between verapamil and
      adenosine but verapamil was associated with the development of transient heart
      block.

PMID- 16449520
TI  - Prospects for atherosclerosis regression through increase in high-density
      lipoprotein and other emerging therapeutic targets.
AB  - In a process often seen as progressive and irreversible, deposition and retention
      of lipoproteins and the consequent inflammatory reaction result in the
      accumulation of atherosclerotic plaques from an early age. However, striking
      effects observed in experimental models support the concept that atherosclerosis
      can regress. This is often accompanied by changes in plaque composition favouring
      stability and decreased likelihood of rupture. Large clinical trials have
      established the value of low-density lipoprotein cholesterol reduction with
      statin treatment, although this may prevent no more than 30% of all
      cardiovascular events, and the magnitude of effect on plaque regression seems
      relatively modest. High-density lipoprotein cholesterol (HDL-C) is well
      recognised as an important and independent protective factor, although treatment
      options to increase HDL-C have until now been limited. The recent emergence of
      new treatments will probably establish increased HDL-C as another important
      strategy in antiatherosclerosis treatment. Beyond HDL-C increases, further
      appreciation of mechanisms of cellular lipid homoeostasis and regulation of gene
      transcription have revealed new targets for atherosclerosis treatment. This
      review considers emerging approaches to plaque regression together with some of
      the parallel developments in imaging technology that will improve our
      appreciation of response to treatment.

PMID- 16449521
TI  - Cerebral autoregulation is impaired in cardioinhibitory carotid sinus syndrome.
AB  - OBJECTIVES: To compare changes in cerebral autoregulation in response to
      controlled, lower body negative pressure-induced hypotension in patients with
      carotid sinus syndrome (CSS) and case controls. DESIGN: Prospective case
      controlled study. SETTING: Secondary and tertiary referral falls and syncope
      service. PATIENTS: 17 consecutive patients with CSS and 11 asymptomatic controls.
      INTERVENTIONS: Hypotension insufficient to cause syncope induced by lower body
      negative pressure (minimum 30 mm Hg fall in systolic blood pressure (SBP)) during
      concomitant transcranial Doppler ultrasonography. MAIN OUTCOME MEASURES: Cerebral
      autoregulation (systolic, diastolic and mean middle cerebral arterial blood flow
      velocities and cerebrovascular resistance) with continuous end-tidal carbon
      dioxide and haemodynamic monitoring. RESULTS: Cerebral autoregulatory indices
      differed significantly between patients with CSS and controls. Systolic,
      diastolic and middle cerebral arterial blood flow velocities were, respectively,
      9.2 m/s (95% confidence interval (CI) 2.9 to 15.4 m/s), 4.7 m/s (95% CI 1.5 to
      7.9 m/s) and 6.9 m/s (95% CI 2.5 to 11.4 m/s) slower in patients with CSS.
      Cerebrovascular resistance was significantly greater in patients with CSS than in
      controls at SBP nadir and suction release; differences were 0.9 mm Hg/m/s (95% CI
      0.0 to 1.7 mm Hg/m/s) and 0.8 mm Hg/m/s (95% CI 0.0 to 1.7 mm Hg/m/s),
      respectively. End-tidal carbon dioxide and systemic haemodynamic variables were
      similar for patients and controls at baseline and during lower body negative
      pressure. CONCLUSIONS: Cerebral autoregulation is altered in patients with CSS.
      This difference may have aetiological implications in the differential
      presentation with falls and drop attacks rather than syncope.

PMID- 16449522
TI  - Treatment of acute graft-versus-host disease with prednisolone: significant
      survival advantage for day +5 responders and no advantage for nonresponders
      receiving anti-thymocyte globulin.
AB  - Newly diagnosed patients with acute graft-versus-host disease (GvHD, grades I-IV;
      n = 211) were given 6-methylprednisolone (6MPred) 2 mg/kg per day for 5
      consecutive days; 150 patients (71%) tapered 6MPred on day +5 and were considered
      responders; 61 patients (29%) could not taper their steroid dose and were
      considered nonresponders. The cumulative incidence of transplant-related
      mortality (TRM) for responders and nonresponders is, respectively, 27% and 49% (P
      = .009), and the 5-year survival is 53% and 35% (P = .007). Nonresponders on day
      +5 (n = 61) were randomized to receive 6MPred 5 mg/kg per day for 10 days alone
      (n = 34) or in combination with rabbit anti-thymocyte globulin (ATG, 6.25 mg/kg
      in 10 days; n = 27). The 2 groups were balanced for clinical and GvHD
      characteristics. One month after randomization, 26% had a complete response; 23%,
      a partial response; 33%, stable GvHD; 10%, worsened; and 8%, died. There was no
      significant difference in response, TRM, and survival between the non-ATG and ATG
      group. In conclusion, 5 days of prednisolone as first-line therapy of acute GvHD
      identifies patients with different risk of TRM, and second-line therapy with a
      combination of 6MPred + ATG does not improve patient outcome, compared with
      6MPred alone.

PMID- 16449524
TI  - Protein-tyrosine kinase Syk is required for pathogen engulfment in complement
      mediated phagocytosis.
AB  - The protein tyrosine kinase Syk plays a central role in Fcgamma receptor-mediated
      phagocytosis in the adaptive immune system. We show here that Syk also plays an
      essential role in complement-mediated phagocytosis in innate immunity. Macrophage
      like differentiated HL60 cells and C3bi-opsonized zymosan comprised the pathogen
      phagocyte system. C3bi-opsonized zymosan particles promptly attached to the cells
      and were subsequently engulfed via complement receptor 3. During this process,
      Syk became tyrosine phosphorylated and accumulated around the nascent phagosomes.
      The transfer of Syk-siRNA or dominant-negative Syk (DN-Syk) into HL60 cells
      resulted in impaired phagocytosis. Quenching assays using fluorescent zymosan
      revealed that most of the attached zymosan particles were located inside parental
      HL60 cells, whereas few were ingested by the mutant cells. These data indicated
      that Syk is required for the engulfment of C3bi-opsonized zymosan. During C3bi
      zymosan-induced phagocytosis, actin accumulation occurred around phagosomes and
      was followed by depolymerization, and further RhoA was activated together with
      tyrosine phosphorylation of Vav. These responses including the actin remodeling
      were suppressed in Syk-siRNA- or DN-Syk-expressing cells. Our results
      demonstrated that Syk plays an indispensable role in complement-mediated
      phagocytosis by regulating both actin dynamics and the RhoA activation pathway
      and that these functions of Syk lead to phagosome formation and pathogen
      engulfment.

PMID- 16449523
TI  - Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or
      R-CHOP: a prospective correlative study.
AB  - Bcl-6 protein expression, a marker of germinal center origin, has been associated
      with a favorable prognosis in diffuse large B-cell lymphoma (DLBCL). To determine
      the prognostic significance of this marker when rituximab (R) was added to
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy,
      we prospectively studied Bcl-6 protein expression by immunohistochemical staining
      of 199 paraffin-embedded specimens from patients enrolled in the US Intergroup
      phase 3 trial comparing R-CHOP to CHOP with or without maintenance R. In Bcl-6(-)
      patients, failure-free survival (FFS) and overall survival (OS) were prolonged
      for those treated with R-CHOP alone compared to CHOP alone (2-year FFS 76% versus
      9%, P < .001; 2-year OS 79% versus 17%, P < .001). In contrast, no differences in
      FFS and OS were detected between treatment arms for Bcl-6(+) cases. In the
      multivariate analysis, treatment arm (CHOP versus R-CHOP) was the major
      determinant of both FFS (P < .001) and OS (P < .001) for the Bcl-6(-) subset,
      whereas the International Prognostic Index risk group was the only significant
      predictor of outcome among Bcl-6(+) cases. Bcl-2 protein expression was not
      predictive of outcome in either group. In this study, we observed a reduction in
      treatment failures and death with the addition of R to CHOP in Bcl-6(-) DLBCL
      cases only. Our finding that Bcl-6(+) cases did not benefit from the addition of
      R to CHOP requires independent confirmation.

PMID- 16449525
TI  - Imatinib as a potential antiresorptive therapy for bone disease.
AB  - Osteoclasts (OCs) are large multinucleated cells derived from progenitor cells of
      the monocyte-macrophage lineage. Signal transduction via the macrophage-colony
      stimulating factor (M-CSF) receptor, c-fms, is essential for OC formation. Since
      we have previously demonstrated inhibition of c-fms by imatinib, we examined the
      effect of imatinib on OC formation and activity. OC formation was not affected by
      concentrations of 1.0 microM imatinib and lower, but was reduced by 75% at 3.0
      microM imatinib. In contrast, both the area of resorption and the number of
      resorption lacunae were reduced by 80% at 0.3 microM imatinib, and no resorption
      was observed at concentrations above 3.0 microM. A dose-dependent decrease in
      receptor activator of nuclear factor kappaB (RANK) expression was observed in OCs
      when cultured in the presence of imatinib, providing a mechanism for the decrease
      in OC function. In vivo analysis of the effect of imatinib on OC activity in
      adult mice following 8 weeks of imatinib treatment also demonstrated a decrease
      in OC activity. These results suggest that imatinib may have therapeutic value as
      an antiosteolytic agent in diseases such as osteoporosis, metastatic bone
      disease, and multiple myeloma.

PMID- 16449526
TI  - Notch1 promotes survival of E2A-deficient T cell lymphomas through pre-T cell
      receptor-dependent and -independent mechanisms.
AB  - Loss of E2A transcription factor activity or activation of the intracellular form
      of Notch1 (ICN) leads to the development of leukemia or lymphoma in humans or
      mice, respectively. Current models propose that ICN functions by suppressing E2A
      through a pre-T cell receptor (TCR)-dependent mechanism. Here we show that
      lymphomas arising in E2A(-/-) mice require the activation of Notch1 for their
      survival and have accumulated mutations in, or near, the Notch1 PEST domain,
      resulting in increased stability and signaling. In contrast, lymphomas arising in
      p53(-/-) mice show the activation of Notch1, but no mutations were identified in
      ICN. The requirement for Notch1 signaling in E2A(-/-) lymphomas cannot be
      overcome by ectopic expression of pTalpha; however, pTalpha is required for
      optimal survival and expansion of these cells. Our findings indicate that the
      activation of Notch1 is an important "second hit" for the transformation of E2A(
      /-) T cell lymphomas and that Notch1 promotes survival through pre-TCR-dependent
      and -independent mechanisms.

PMID- 16449527
TI  - Mechanism of platelet adhesion to von Willebrand factor and microparticle
      formation under high shear stress.
AB  - We describe here the mechanism of platelet adhesion to immobilized von Willebrand
      factor (VWF) and subsequent formation of platelet-derived microparticles mediated
      by glycoprotein Ibalpha (GPIbalpha) under high shear stress. As visualized in
      whole blood perfused in a flow chamber, platelet attachment to VWF involved one
      or few membrane areas of 0.05 to 0.1 microm(2) that formed discrete adhesion
      points (DAPs) capable of resisting force in excess of 160 pN. Under the influence
      of hydrodynamic drag, membrane tethers developed between the moving platelet body
      and DAPs firmly adherent to immobilized VWF. Continued stretching eventually
      caused the separation of many such tethers, leaving on the surface tube-shaped or
      spherical microparticles with a diameter as low as 50 to 100 nm. Adhesion
      receptors (GPIbalpha, alphaIIbbeta3) and phosphatidylserine were expressed on the
      surface of these microparticles, which were procoagulant. Shearing platelet-rich
      plasma at the rate of 10,000 s(-1) in a cone-and-plate viscosimeter increased
      microparticle counts up to 55-fold above baseline. Blocking the GPIb-VWF
      interaction abolished microparticle generation in both experimental conditions.
      Thus, a biomechanical process mediated by GPIbalpha-VWF bonds in rapidly flowing
      blood may not only initiate platelet arrest onto reactive vascular surfaces but
      also generate procoagulant microparticles that further enhance thrombus
      formation.

PMID- 16449528
TI  - High-level expression of porcine factor VIII from genetically modified bone
      marrow-derived stem cells.
AB  - Clinical success for gene therapy of hemophilia A will be judged by achievement
      of sustained, therapeutic levels of coagulation factor VIII (fVIII). Previous
      clinical trials have suffered from transient, subtherapeutic expression of human
      fVIII transgenes. Porcine fVIII contains sequence elements that enable more
      efficient biosynthesis than human fVIII due to enhanced posttranslational transit
      through the secretory pathway. In this study, we evaluated ex vivo retroviral
      gene transfer of a high-expression porcine fVIII transgene into bone marrow
      derived stromal and hematopoietic stem/progenitor cells (MSCs and HSCs,
      respectively) and transplantation into genetically immunocompetent hemophilia A
      mice. Both MSCs and HSCs demonstrated high-level expression of porcine fVIII in
      vivo. However, following transplantation of gene-modified MSCs, fVIII activity
      levels rapidly returned to baseline due to the formation of anti-porcine fVIII
      neutralizing antibodies. Alternatively, transplantation of HSCs into myeloablated
      and nonmyeloablated hemophilia A mice resulted in high-level fVIII expression
      despite low-level hematopoietic reconstitution by gene-modified cells. FVIII
      expression was sustained beyond 10 months, indicating that immunologic tolerance
      to porcine fVIII was achieved. Furthermore, transplantation of bone marrow from
      primary recipients into naive secondary recipients resulted in sustained, high
      level fVIII expression demonstrating successful genetic modification and
      engraftment of HSCs.

PMID- 16449529
TI  - Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: role of
      phosphatidylinositol 3-kinase signaling in the glycolytic control of growth.
AB  - The bioenergetic response of B lymphocytes is subject to rapid changes following
      antigen encounter in order to provide ATP and anabolic precursors necessary to
      support growth. However, the pathways involved in glucose acquisition and
      metabolism are unknown. We find that B lymphocytes rapidly increase glucose
      uptake and glycolysis following B-cell antigen receptor (BCR) crosslinking.
      Inhibition of glycolysis blocks BCR-mediated growth. Prior to S-phase entry,
      glucose metabolism shifts from primarily glycolytic to include the pentose
      phosphate pathway. BCR-induced glucose utilization is dependent upon
      phosphatidylinositol 3-kinase (PI-3K) activity as evidenced by inhibition of
      glucose uptake and glycolysis with LY294002 treatment of normal B cells and
      impaired glucose utilization in B cells deficient in the PI-3K regulatory subunit
      p85alpha. Activation of Akt is sufficient to increase glucose utilization in B
      cells. We find that glucose utilization is inhibited by coengagement of the BCR
      and FcgammaRIIB, suggesting that limiting glucose metabolism may represent an
      important mechanism underlying FcgammaRIIB-mediated growth arrest. Taken
      together, these findings demonstrate that both growth-promoting BCR signaling and
      growth-inhibitory FcgammaRIIB signaling modulate glucose energy metabolism.
      Manipulation of these pathways may prove to be useful in the treatment of
      lymphoproliferative disorders, wherein clonal expansion of B lymphocytes plays a
      role.

PMID- 16449531
TI  - CD8+ T-cell-mediated killing of donor dendritic cells prevents alloreactive T
      helper type-2 responses in vivo.
AB  - Accumulating evidence indicates that, in absence of CD8+ T-cell activation, CD4+
      T-cell-mediated allograft rejection is associated with a dominant Th2-cell
      response and eosinophil infiltrates. In this study, we analyzed the mechanisms by
      which CD8+ T cells regulate alloreactive CD4+ T-cell priming and differentiation
      into interleukin 4 (IL-4)-producing cells. We showed that interferon gamma (IFN
      gamma) production by CD8+ T cells was dispensable for the inhibition of Th2-cell
      development, as well as tissue eosinophilia and type 2 cytokine production in the
      rejected grafts. Since we noticed that CD8+ T cells not only suppressed Th2
      differentiation, but also down-modulated the overall priming of alloreactive CD4+
      T cells, we evaluated whether CD8+ T cells act by limiting the accumulation of
      donor-derived dendritic cells (DCs) in lymph nodes. We found that indeed,
      alloreactive CD8+ T cells rapidly eliminated allogeneic DCs from T-cell areas of
      draining lymph nodes, through a perforin-dependent mechanism. Thus, our data
      demonstrate that cytotoxic T lymphocyte (CTL)-mediated clearance of allogeneic
      DCs is a negative feedback mechanism that limits the duration of alloantigen
      presentation in draining lymph nodes, thereby modulating the amplitude and
      polarization of the primary alloreactive CD4+ T-cell responses.

PMID- 16449532
TI  - c-Myc acts downstream of IL-15 in the regulation of memory CD8 T-cell
      homeostasis.
AB  - A subset of CD8 T cells in normal mice, expressing high levels of activation
      markers such as CD44, shares many properties with antigen-specific memory CD8 T
      cells. Homeostasis of CD44(high) CD8 T cells depends upon cytokines such as
      interleukin-15 (IL-15); however, the downstream signaling pathways regulating IL
      15-dependent homeostatic proliferation are poorly defined. Surprisingly, we show
      here that haploinsufficiency of the protooncogene c-myc leads to a highly
      selective decrease in CD44(high) CD8 T cells in mice. Although steady-state
      proliferation and survival of CD44(high) CD8 T cells appeared not to be dependent
      on c-Myc, homeostatic proliferation of c-myc(+/-) CD44(high) CD8 T cells in
      lymphopenic hosts was strongly reduced, and the residual homeostatic
      proliferation of these cells appeared to occur independently of IL-15. Moreover,
      c-myc(+/-) CD44(high) CD8 T cells responded very poorly to purified IL-15 in
      vitro. Backcrossing of c-myc(+/-) mice to IL-15(-/-) mice revealed that the
      number of CD44(high) CD8 T cells decreased in an additive fashion in mice
      heterozygous for c-myc and IL-15. Finally homeostatic proliferation of antigen
      specific memory CD44(high) CD8 T cells was also impaired in c-myc(+/-) mice.
      Collectively, our data identify c-Myc as a novel downstream component of the IL
      15-dependent pathway controlling homeostatic proliferation of memory CD44(high)
      CD8 T cells.

PMID- 16449530
TI  - Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin
      lymphoma.
AB  - Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes
      can alter gene expression, modulate the balance between Th1/Th2 responsiveness,
      and influence susceptibility for autoimmune disorders, infectious diseases, and
      cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20
      candidate Th1/Th2 genes in a population-based case-control study of non-Hodgkin
      lymphoma (NHL; n = 518 cases, 597 controls) among women in Connecticut. SNPs in
      critical genes, IL4, IL5, IL6, and IL10, were associated with risk for NHL and in
      some instances with a specific histologic subtype. Analysis of 4 SNPs in the IL10
      promoter (-3575T>A, -1082A>G, -819C>T, and -592C>A) revealed that both the AGCC
      haplotype (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.21-1.96, P <
      .001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = .02) were
      associated with increased risk for B-cell lymphomas. In contrast, the IL4-1098G
      allele was associated with increased risk of T-cell lymphomas (OR = 3.84; 95% CI
      = 1.79-8.22; P < .001). Further, the IL10 and IL4 SNP associations remained
      significant after adjusting for multiple comparisons. These results suggest that
      SNPs in Th2 cytokine genes may be associated with risk of NHL.

PMID- 16449535
TI  - Hydrogen peroxide burn of the oral mucosa.

PMID- 16449533
TI  - Clinical significance of minimal residual disease, as assessed by different
      techniques, after stem cell transplantation for chronic lymphocytic leukemia.
AB  - We analyzed minimal residual disease (MRD) by consensus polymerase chain reaction
      (PCR), quantitative PCR (qPCR), and flow cytometry in 40 patients with chronic
      lymphocytic leukemia (CLL) who underwent stem cell transplantation; 97.4%, 89%,
      and 100% of the patients could be studied by consensus PCR, qPCR, and flow
      cytometry, respectively. Overall, 164 of 248 samples were negative for MRD by
      consensus PCR. Among those, CLL cells were detected by qPCR and by flow cytometry
      in 77 (47%) and 39 (23%) of the 164 samples, respectively. All 84 samples
      positive on PCR had detectable CLL cells by qPCR and flow cytometry. A good
      correlation was seen between MRD levels by flow cytometry and by qPCR (n = 254; r
      = 0.826; P < .001). Fifteen of 25 patients receiving autografts suffered a
      relapse, with increasing levels of MRD being observed before relapse in all of
      them. MRD detection within the first 6 months after autologous transplantation
      identified patients with a high relapse risk. In contrast, in allografted
      patients (n = 15) MRD did not correlate with outcome. In conclusion, quantitative
      methods to assess MRD (flow cytometry and qPCR) are more accurate than consensus
      PCR to predict clinical evolution. These results might be useful to investigate
      treatments aimed at preventing relapse in patients with CLL who have received an
      autograft.

PMID- 16449534
TI  - Serial measurement of BCR-ABL transcripts in the peripheral blood after
      allogeneic stem cell transplantation for chronic myeloid leukemia: an attempt to
      define patients who may not require further therapy.
AB  - We identified 243 patients with Philadelphia (Ph) chromosome-positive chronic
      myeloid leukemia (CML) who had BCR-ABL transcripts monitored by quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) after allogeneic stem
      cell transplantation for a median of 84.3 months. Individual patients were
      regarded as having achieved molecular relapse (MR) if the BCR-ABL/ABL ratio
      exceeded 0.02% on 3 occasions or reached 0.05% on 2 occasions. Patients were
      allocated to 1 of 4 categories: (1) 36 patients were "persistently negative" or
      had a single low-level positive result; (2) 51 patients, "fluctuating positive,
      low level," had more than 1 positive result but never more than 2 consecutive
      positive results; (3) 27 patients, "persistently positive, low level," had
      persisting low levels of BCR-ABL transcripts but never more than 3 consecutive
      positive results; and (4) 129 patients relapsed. In 107 of these, relapse was
      based initially only on molecular criteria; in 72 (67.3%) patients the leukemia
      progressed to cytogenetic or hematologic relapse either prior to or during
      treatment with donor lymphocyte infusions. We conclude that the pattern of BCR
      ABL transcript levels after allograft is variable; only a minority of patients
      with fluctuating or persistent low levels of BCR-ABL transcripts satisfied our
      definitions of MR, whereas the majority of patients who did so were likely to
      progress further.

PMID- 16449536
TI  - A personal view of the history and future direction of drug information.

PMID- 16449537
TI  - Successful clearance of catheter-related bloodstream infection by antibiotic lock
      therapy using ampicillin.
AB  - OBJECTIVE: To report a case in which ampicillin was used successfully as lock
      therapy for a central venous intravascular catheter and to discuss the
      implications of ampicillin used in this modality. CASE SUMMARY: A 14-month-old
      girl with a long-term central venous catheter acquired a polymicrobial
      (Escherichia coli and Enterococcus durans) bloodstream infection. The central
      venous catheter was suspected as the source for the bacteremia based on the
      timing and number of positive blood cultures in relation to therapy with
      antibiotics. Antibiotic sensitivity testing revealed ampicillin monotherapy to be
      an ideal choice to treat both organisms. A combination of systemic therapy via a
      temporary catheter and antibiotic lock therapy of the central venous catheter was
      then instituted using ampicillin without anticoagulants. The patient tolerated
      this therapy without complications, and follow-up cultures demonstrated effective
      clearance of the bacteria. DISCUSSION: Antibiotic lock therapy has been shown to
      be useful in the treatment of catheter-related bloodstream infections. However,
      many antibiotics have yet to be tested with this modality. Ampicillin, which is
      frequently used in the treatment of Enterococcus and E. coli infections, has not
      previously been reported as a single agent for lock therapy. CONCLUSIONS:
      Ampicillin may be a useful agent with the relatively new modality of lock therapy
      for central venous catheters. Further studies are needed to demonstrate possible
      compatibility of this agent with anticoagulants, such as heparin, as well as its
      efficacy in treating catheter-related bloodstream infections.

PMID- 16449538
TI  - Nonconvulsive status epilepticus due to ifosfamide.
AB  - OBJECTIVE: To report 2 cases of nonconvulsive status epilepticus (NCSE) following
      infusion of ifosfamide. CASE SUMMARIES: Two patients who received ifosfamide
      containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2
      (1 h infusion on days 1-5); confusion, lethargy, and speech deterioration
      developed on day 3. The second patient developed similar symptoms on day 3 of
      treatment with 2500 mg/m2. Both patients responded to intravenous administration
      of diazepam 10 mg and were given levetiracetam as maintenance therapy.
      DISCUSSION: The severity and presentation of central nervous system toxicity due
      to ifosfamide varies greatly and involves a spectrum ranging from subclinical
      electroencephalogram changes to coma. NCSE, an epileptic disorder in which
      typical convulsive activity is absent, has previously been reported in only 4
      patients receiving ifosfamide. Levetiracetam may be used for maintenance
      antiepileptic therapy after diazepam administration. CONCLUSIONS: Among the many
      presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a
      possible explanation for changes in consciousness in a patient receiving this
      agent. An objective causality assessment by use of the Naranjo probability scale
      revealed that NCSE due to ifosfamide was probable.

PMID- 16449540
TI  - Modified-release tacrolimus.
AB  - OBJECTIVE: To review the pharmacokinetics, efficacy, adverse effects, and
      clinical trials of modified-release tacrolimus (MR-4) concerning its equivalence
      to non-modified-release tacrolimus. DATA SOURCES: A PubMed/MEDLINE search was
      conducted (1966-July 2005) using the following terms: MR-4, tacrolimus, FK506,
      Prograf, transplantation, calcineurin inhibitors, and immunosuppression.
      Additional data sources included meeting abstracts, bibliographies from
      identified publications, and information from the manufacturer. STUDY SELECTION
      AND DATA EXTRACTION: All English-language, published, randomized clinical trials
      evaluating MR-4 were included in this review. Clinical trials that used
      tacrolimus for the prevention of solid-organ graft rejection were also selected
      from the data sources. DATA SYNTHESIS: Studies demonstrated that MR-4 has
      pharmacokinetic profiles similar to those of tacrolimus in healthy volunteers,
      renal transplant recipients, and liver transplant recipients. Similar efficacy
      and safety profiles have also been demonstrated. Data also suggest that the
      target whole blood trough concentration range of MR-4 is similar to that of
      tacrolimus and that it is safe to convert from tacrolimus twice daily to MR-4
      once daily using a 1:1 conversion. CONCLUSIONS: Short-term clinical trials
      indicated that MR-4 has efficacy and safety profiles similar to those of
      tacrolimus. MR-4's once-daily dosing offers an advantage over the currently
      available calcineurin inhibitors in preventing graft rejection. However,
      adherence studies with MR-4 that measure clinical and economic outcomes are
      needed.

PMID- 16449539
TI  - Bivalirudin use in carotid endarterectomy in a patient with heparin-induced
      thrombocytopenia.
AB  - OBJECTIVE: To describe the successful use of bivalirudin as the primary
      procedural anticoagulant in a patient with suspected heparin-induced
      thrombocytopenia (HIT) undergoing carotid endarterectomy (CEA). CASE SUMMARY: A
      73-year-old white man presented for an elective CEA 3 weeks after emergent, on
      pump coronary artery bypass grafting. Bivalirudin was used for procedural
      anticoagulation because of seropositivity for heparin-PF4 antibodies and a
      clinical history consistent with HIT. The dose was administered as a 0.75 mg/kg
      bolus and 1.75 mg/kg/h infusion as reported in percutaneous coronary
      intervention, based on review of the available bivalirudin literature. The dosage
      was adjusted for the patient's renal dysfunction. The outcome was successful,
      with the patient discharged home in 8 days without significant complications.
      DISCUSSION: During active HIT, when thrombocytopenia and heparin-PF4 antibodies
      are present, heparin therapy must be avoided. In patients with subacute HIT, when
      platelet counts have recovered but HIT antibodies are still present, it is also
      prudent to avoid heparin administration. In the case of a patient in whom
      anticoagulation is necessary but heparin use is contraindicated, a direct
      thrombin inhibitor, such as bivalirudin, may offer a viable alternative.
      Bivalirudin is not immunogenic and does not cross-react with the heparin-PF4
      antibodies associated with HIT. To our knowledge, as of January 20, 2006, this is
      the first report of the use of bivalirudin for procedural anticoagulation during
      CEA in a patient with HIT antibodies and recent exposure to heparin. CONCLUSIONS:
      Further investigation is warranted to clarify the clinical benefits of
      bivalirudin for patients undergoing vascular surgery of the carotids, including
      potential advantages for vulnerable patient populations such as those with
      diagnosed or suspected HIT as well as those with renal dysfunction.

PMID- 16449541
TI  - Nonfatal, unintentional medication exposures among young children--US, 2001-2003.

PMID- 16449542
TI  - Recommended childhood and adolescent immunization schedule--US, 2006.

PMID- 16449543
TI  - Considerations for supplementing with coenzyme Q10 during statin therapy.
AB  - OBJECTIVE: To review the literature concerning the effects of statin use on
      coenzyme (Co) Q10 concentrations and explain the rationale behind considering
      CoQ10 supplementation. DATA SOURCES: A MEDLINE search was conducted through
      January 2006. Search terms included ubiquinone, coenzyme Q10, HMG-CoA reductase
      inhibitors, statins, myotoxicity, and clinical trials. DATA SYNTHESIS: Statin
      therapy reduces blood CoQ10 concentrations. Studies exploring how this affects
      the development of myotoxicity have been small and dissimilar, thus limiting the
      ability to draw strong conclusions. Isolated studies suggested that statins
      induce mitochondrial dysfunction, but the clinical implications of this effect
      are limited. Limited data suggest that patients with familial
      hypercholesterolemia, heart failure, or who are over 65 years of age might
      represent at-risk populations who would benefit from CoQ10 supplementation.
      CONCLUSIONS: Routine CoQ10 supplementation for all patients taking statins to
      prevent myotoxicity is not recommended. However, certain subpopulations might be
      at risk and warrant further study.

PMID- 16449545
TI  - Comment: comparisons of Aralast and Prolastin, alpha1-protease inhibitors for
      treatment of alpha1-antitrypsin deficiency.

PMID- 16449546
TI  - Meropenem by continuous versus intermittent infusion in ventilator-associated
      pneumonia due to gram-negative bacilli.
AB  - BACKGROUND: It is known that beta-lactam antibiotics exhibit time-dependent
      bactericidal activity. Several studies have found continuous infusion of
      meropenem more effective than intermittent infusion in maintaining constant serum
      concentrations in excess of the minimum inhibitory concentration. However,
      limited data exist on the clinical efficacy of meropenem administered by
      continuous infusion. OBJECTIVE: To evaluate the clinical efficacy of continuous
      versus intermittent infusion of meropenem for the treatment of ventilator
      associated pneumonia (VAP) due to gram-negative bacilli. METHODS: A retrospective
      cohort study was conducted of patients with VAP caused by gram-negative bacilli
      who received initial empiric antibiotic therapy with meropenem. We analyzed 2
      contemporary cohorts: one group received meropenem by continuous infusion (1 g
      over 360 min every 6 h), the other by intermittent infusion (1 g over 30 min
      every 6 h). The administration method was prescribed according to the physician's
      discretion. Patients received meropenem plus tobramycin for 14 days. RESULTS:
      There were no significant differences between patient groups with regard to
      gender, age, APACHE-II at intensive care unit admission, diagnosis, microorganism
      responsible for VAP, or organ dysfunction severity at the time VAP was suspected.
      The group receiving medication by continuous infusion showed a greater clinical
      cure rate than the group treated with intermittent infusion (38 of 42, 90.47%, vs
      28 of 47, 59.57%, respectively, with OR 6.44 [95% CI 1.97 to 21.05; p < 0.001]).
      CONCLUSIONS: Meropenem administered by continuous infusion may have more clinical
      efficacy than intermittent infusion.

PMID- 16449547
TI  - Successful recovery after an overdose of argatroban.
AB  - OBJECTIVE: To report the case of a critically ill man with heparin-induced
      thrombocytopenia (HIT) who received a 125 mg overdose of the direct thrombin
      inhibitor argatroban. CASE SUMMARY: A 74-year-old man with a history of Crohn's
      disease underwent takedown of an ileorectal fistula. He developed HIT
      postoperatively and was treated with argatroban. He became critically ill and was
      transferred to the intensive care unit. On postoperative day 24, he accidentally
      received argatroban 125 mg over 1 hour (26 microg/kg/min). Treatment with fresh
      frozen plasma (FFP) was effective, and there were no significant complications.
      The partial thromboplastin time, however, continued to be prolonged 48 hours
      after the overdose. DISCUSSION: Medication errors with direct thrombin inhibitors
      are common. However, there is no known reversal agent for this class of
      anticoagulants. This patient was treated with FFP and did well, with no bleeding
      complications. However, the clearance of argatroban was prolonged. CONCLUSIONS:
      This case illustrates that supratherapeutic doses of argatroban can be managed
      with FFP and tolerated without significant complications.

PMID- 16449548
TI  - Emerging role of epidemiologic literacy.
AB  - BACKGROUND: The ability to understand and apply epidemiology methods is a growing
      part of pharmacy practice, pharmacy accreditation standards, and evidence-based
      practice. OBJECTIVE: To examine the trends in epidemiology-related terminology
      used in the literature over the past 20 years. METHODS: The frequency of the use
      of epidemiology-related terminology in 3 representative pharmacy journals, 2
      representative medical journals, and 1 public health journal from January through
      December 1984, 1994, and 2004 was recorded. The 3 pharmacy journals were the
      American Journal of Health-System Pharmacy (formerly American Journal of Hospital
      Pharmacy), The Annals of Pharmacotherapy (formerly Drug Intelligence and Clinical
      Pharmacy), and Pharmacotherapy. The 2 medical journals were the New England
      Journal of Medicine and The Journal of the American Medical Association (JAMA),
      and the public health journal was the American Journal of Public Health. The
      number of times an epidemiology-related term was used was summed for each year
      and each journal. RESULTS: For all the journals examined in this study combined,
      the proportion of epidemiologic terms used in the literature has increased over
      the past 20 years. In 1984, of the total articles published in the 6 journals,
      7.02% contained epidemiologic terms increasing to 12.27% and 15.46% in 1994 and
      2004, respectively. The most dramatic differences in the 20-year comparisons were
      noted for Pharmacotherapy (0 to 17.75%) and JAMA (7.32 to 26.72%). CONCLUSIONS:
      The increase in the use of epidemiology-related terms has implications for both
      curricular planning in schools and colleges of pharmacy, as well as for
      continuing education programs and effective interprofessional communication.

PMID- 16449549
TI  - Erythropoietin dose requirements when converting from subcutaneous to intravenous
      administration among patients on hemodialysis.
AB  - BACKGROUND: The optimal route for administration of exogenous erythropoietin
      remains controversial, particularly after the increased incidence in pure red
      cell aplasia. In Canada, the majority of hemodialysis units have converted to the
      intravenous route for administration of erythropoietin to potentially decrease
      the risk of pure red cell aplasia. OBJECTIVE: To compare the difference in the
      weight-adjusted, weekly erythropoietin dose (units/kg/wk) administered by the
      subcutaneous compared with the intravenous route in a chronic hemodialysis
      population followed for 12 months. METHODS: This prospective cohort study
      recruited patients receiving subcutaneous erythropoietin for at least 3 months
      while undergoing dialysis in a tertiary care hemodialysis program. Participants
      were switched to intravenous erythropoietin, and the average weekly dose was
      recorded at 1, 2, 3, 6, and 12 months. Anemia management and hemoglobin, iron,
      and delivered dialysis dose targets remained constant throughout the study.
      RESULTS: The erythropoietin dose increased by 24.5 units/kg/wk (95% CI 12.7 to
      36.3; p < 0.001), representing a 20.2% increase (95% CI 10.5% to 29.9%; p <
      0.001) 12 months after conversion from the subcutaneous to intravenous route of
      administration. Both patients with and without residual renal function at
      baseline required a significant increase in the intravenous dose. CONCLUSIONS: A
      20.2% increase in erythropoietin dose was required to maintain hemoglobin targets
      between 11 and 12 g/dL after conversion from a subcutaneous to intravenous
      formulation. Healthcare funding agencies need to reexamine the cost benefit of
      using intravenous erythropoietin in the hemodialysis population with a low
      incidence of pure red cell aplasia.

PMID- 16449550
TI  - Drug-gene interaction between the insertion/deletion polymorphism of the
      angiotensin-converting enzyme gene and antihypertensive therapy.
AB  - BACKGROUND: Despite the availability of a variety of effective drugs, inadequate
      control of blood pressure is common. There are some indications that the
      angiotensin-converting enzyme (ACE) gene modifies the response to
      antihypertensive drugs, but the results have been inconclusive. OBJECTIVE: To
      investigate whether the insertion/deletion polymorphism of the ACE gene modifies
      blood pressure differences among subjects using diuretics, beta-blockers, calcium
      channel antagonists, or ACE inhibitors. METHODS: Data were used from the
      Rotterdam Study, a population-based, prospective, cohort study in the
      Netherlands, which started in 1990 and included 7983 subjects aged 55 years or
      older. Data from 3 subsequent cross-sectional investigations were used, as well.
      Subjects were included if they had high blood pressure during one or more
      examinations and/or used monotherapy with a diuretic, beta-blocker, calcium
      channel antagonist, or ACE inhibitor. A marginal, generalized, linear model was
      used to assess the association between the mean difference in systolic/diastolic
      blood pressure and antihypertensive classes stratified by the 3 genotypes.
      RESULTS: In total, 3025 hypertensive individuals were included, and 6500
      measurements of blood pressure were taken. The percentages of DD, ID, and II
      genotypes were 28.3%, 51.4%, and 20.3%, respectively. The mean differences in
      systolic blood pressure between the II and DD genotypes were 0.23 mm Hg (95% CI 
      5.48 to 5.94) for diuretics, -2.41 mm Hg (95% CI -6.72 to 1.90) for beta
      blockers, 2.12 mm Hg (95% CI -4.64 to 8.89) for calcium-channel antagonists, and 
      2.01 mm Hg (95% CI -9.82 to 5.79) for ACE inhibitors. CONCLUSIONS: The adjusted
      mean difference in diastolic and systolic blood pressure among diuretic, beta
      blocker, calcium-channel antagonist, or ACE inhibitor users was not modified by
      the ACE insertion/deletion polymorphism.

PMID- 16449551
TI  - Lanthanum carbonate.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and
      safety profile of lanthanum carbonate, a phosphate binder for chronic kidney
      disease (CKD). DATA SOURCES: Information was selected from PubMed (1965-October
      2005). All studies presented as scientific posters and abstracts from nephrology
      meetings from 1999 to 2005 were also included. STUDY SELECTION AND DATA
      EXTRACTION: All published articles regarding lanthanum carbonate were included.
      In addition, abstracts and presentations from scientific meeting symposia were
      also considered for inclusion. DATA SYNTHESIS: Lanthanum carbonate has been
      recently approved as non-calcium-based therapy for phosphate reduction in
      patients with stage 5 CKD requiring dialysis. The recommended dose is 250-500 mg
      with meals, for a maximum of 1500 mg daily. Clinical studies have shown short-
      and long-term safety with lanthanum carbonate administration. Adverse effects
      were primarily gastrointestinal in nature. Clinical trials have also shown
      reductions in serum phosphorus to target concentrations, reductions in associated
      calcium-phosphorus product, and minimal effects on serum calcium and parathyroid
      hormone concentrations. CONCLUSIONS: Lanthanum carbonate is an effective
      phosphate-binding agent without significant risk of hypercalcemia or worsening
      metabolic acidosis. Lanthanum carbonate is a safe and effective drug for
      reduction of elevated serum phosphorus levels associated with stage 5 CKD. The
      role of lanthanum carbonate relative to other phosphate-binding drugs, such as
      calcium salts and sevelamer, remains to be determined.

PMID- 16449552
TI  - Cannabinoid analgesia as a potential new therapeutic option in the treatment of
      chronic pain.
AB  - OBJECTIVE: To review the literature concerning the physiology of the
      endocannabinoid system, current drug development of cannabinoid agonists, and
      current clinical research on the use of cannabinoid agonists for analgesia. DATA
      SOURCES: Articles were identified through a search of MEDLINE (1966-August 2005)
      using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC,
      pain, and analgesia. No search limits were included. Additional references were
      located through review of the bibliographies of the articles identified. STUDY
      SELECTION AND DATA EXTRACTION: Studies of cannabinoid agonists for treatment of
      pain were selected and were not limited by pain type or etiology. Studies or
      reviews using animal models of pain were also included. Articles that related to
      the physiology and pharmacology of the endocannabinoid system were evaluated.
      DATA SYNTHESIS: The discovery of cannabinoid receptors and endogenous ligands for
      these receptors has led to increased drug development of cannabinoid agonists.
      New cannabimimetic agents have been associated with fewer systemic adverse
      effects than delta-9-tetrahydrocannabinol, including recent development of
      cannabis medicinal extracts for sublingual use (approved in Canada), and have had
      promising results for analgesia in initial human trials. Several synthetic
      cannabinoids have also been studied in humans, including 2 cannabinoid agonists
      available on the international market. CONCLUSIONS: Cannabinoids provide a
      potential approach to pain management with a novel therapeutic target and
      mechanism. Chronic pain often requires a polypharmaceutical approach to
      management, and cannabinoids are a potential addition to the arsenal of treatment
      options.

PMID- 16449553
TI  - The V-type H+ ATPase: molecular structure and function, physiological roles and
      regulation.
AB  - It was nearly 30 years before the V-type H+ ATPase was admitted to the small
      circle of bona fide transport ATPases alongside F-type and P-type ATPases. The V
      type H+ ATPase is an ATP-driven enzyme that transforms the energy of ATP
      hydrolysis to electrochemical potential differences of protons across diverse
      biological membranes via the primary active transport of H+. In turn, the
      transmembrane electrochemical potential of H+ is used to drive a variety of (i)
      secondary active transport systems via H+-dependent symporters and antiporters
      and (ii) channel-mediated transport systems. For example, expression of Cl-
      channels or transporters next to the V-type H+ ATPase in vacuoles of plants and
      fungi and in lysosomes of animals brings about the acidification of the endosomal
      compartment, and the expression of the H+/neurotransmitter antiporter next to the
      V-type H+ ATPase concentrates neurotransmitters in synaptic vesicles. First found
      in association with endosomal membranes, the V-type H+ ATPase is now also found
      in increasing examples of plasma membranes where the proton pump energizes
      transport across cell membranes and entire epithelia. The molecular details
      reveal up to 14 protein subunits arranged in (i) a cytoplasmic V1 complex, which
      mediates the hydrolysis of ATP, and (ii) a membrane-embedded V0 complex, which
      translocates H+ across the membrane. Clever experiments have revealed the V-type
      H+ ATPase as a molecular motor akin to F-type ATPases. The hydrolysis of ATP
      turns a rotor consisting largely of one copy of subunits D and F of the V1
      complex and a ring of six or more copies of subunit c of the V0 complex. The
      rotation of the ring is thought to deliver H+ from the cytoplasmic to the
      endosomal or extracellular side of the membrane, probably via channels formed by
      subunit a. The reversible dissociation of V1 and V0 complexes is one mechanism of
      physiological regulation that appears to be widely conserved from yeast to animal
      cells. Other mechanisms, such as subunit-subunit interactions or interactions of
      the V-type H+ ATPase with other proteins that serve physiological regulation,
      remain to be explored. Some diseases can now be attributed to genetic alterations
      of specific subunits of the V-type H+ ATPase.

PMID- 16449554
TI  - Dynamics of the aerial maneuvers of spinner dolphins.
AB  - The spinner dolphin (Stenella longirostris) performs spectacular leaps from the
      water while rotating around its longitudinal axis up to seven times. Although
      twisting of the body while airborne has been proposed as the mechanism to effect
      the spin, the morphology of the dolphin precludes this mechanism for the spinning
      maneuver. A mathematical model was developed that demonstrates that angular
      momentum to induce the spin was generated underwater, prior to the leap.
      Subsurface corkscrewing motion represents a balance between drive torques
      generated by the flukes and by hydrodynamic forces at the pectoral fins, and
      resistive torques, induced by the drag forces acting on the rotating control
      surfaces. As the dolphin leaps clear of the water, this balance is no longer
      maintained as the density of the air is essentially negligible, and a net drive
      torque remains, which permits the dolphin's rotation speed to increase by as much
      as a factor of three for a typical specimen. The model indicates that the high
      rotation rates and orientation of the dolphin's body during re-entry into the
      water could produce enough force to hydrodynamically dislodge unwanted remoras.

PMID- 16449555
TI  - Microtubule-dependent relocation of branchial V-H+-ATPase to the basolateral
      membrane in the Pacific spiny dogfish (Squalus acanthias): a role in base
      secretion.
AB  - We have previously shown that continuous intravenous infusion of NaHCO3 for 24 h
      ( approximately 1000 micromol kg(-1) h(-1)) results in the relocation of V-H+
      ATPase from the cytoplasm to the basolateral membrane in the gills of the Pacific
      dogfish. To further investigate this putative base-secretive process we performed
      similar experiments with the addition of colchicine, an inhibitor of cytoskeleton
      dependent cellular trafficking processes. Blood pH and plasma total CO2 were
      significantly higher in the colchicines-treated, HCO3- -infused fish compared
      with fish infused with HCO3- alone. The effect of colchicine was highest after 24
      h of infusion (8.33+/-0.06 vs 8.02+/-0.03 pH units, 15.72+/-3.29 vs 6.74+/-1.34
      mmol CO2 l(-1), N=5). Immunohistochemistry and western blotting confirmed that
      colchicine blocked the transit of V-H+-ATPase to the basolateral membrane.
      Furthermore, western blotting analyses from whole gill and cell membrane samples
      suggest that the short-term (6 h) response to alkaline stress consists of
      relocation of V-H+-ATPases already present in the cell to the basolateral
      membrane, while in the longer term (24 h) there is both relocation of preexistent
      enzyme and upregulation in the synthesis of new units. Our results strongly
      suggest that cellular relocation of V-H+-ATPase is necessary for enhanced HCO3-
      secretion across the gills of the Pacific dogfish.

PMID- 16449557
TI  - Constrained optimization in human running.
AB  - Walking humans spontaneously select different speed, frequency and step length
      combinations, depending on which of these three parameters is specified. This
      behavior can be explained by constrained optimization of cost of transport
      (metabolic cost/distance) where cost of transport is seen as the main component
      of an underlying objective function that is minimized within the limitations of
      specified constraints. It is then of interest to ask whether or not such results
      are specific to walking only, or indicate a more general feature of locomotion
      control. The current study examines running gait selection within the framework
      of constrained optimization by comparing self-selected running gaits to the gaits
      predicted by constrained optimization of a cost surface constructed from cost
      data available in the literature. Normalizing speed and frequency values in the
      behavioral data by preferred speed and frequency reduced inter-subject
      variability and made group behavioral trends more visible. Although actual
      behavior did not coincide exactly with running cost optimization, self-selected
      gait and predictions from the general human cost surface did agree to within the
      95% confidence interval and the region of minimal cost+0.005 ml O2 kg(-1) m(-1).
      This was similar to the level of agreement between actual and predicted behavior
      observed in walking. Thus, there seems to be substantial evidence to suggest that
      (i) selection of gait parameters in running can largely be predicted using
      constrained optimization, and (ii) general cost surfaces can be constructed using
      metabolic data from one group that will largely predict the behavior of other
      groups.

PMID- 16449556
TI  - Asymmetric craniofacial remodeling and lateralized behavior in larval flatfish.
AB  - Flatfishes, such as flounder, are the world's most asymmetric vertebrates. It is
      unknown if the development of lateralized swimming behavior during metamorphosis
      is an adaptive response to bilaterally asymmetric eye positioning, or if this
      results from a vestibular response to thyroid hormone. This study describes
      larval development in left-sided, right-sided and bilaterally symmetric variants
      of southern flounder (Paralichthys lethostigma). Behavior and skull asymmetries
      precede metamorphosis, and the development of lateralized behaviors was
      independent of eye position in larvae treated with thyroid hormone and in
      symmetrical variants. Therefore, lateralized behavior is not an adaptive response
      to eye translocation, but rather must result from changing vestibular responses
      to thyroid hormone.

PMID- 16449558
TI  - Effects of limb mass distribution on mechanical power outputs during
      quadrupedalism.
AB  - Many researchers have suggested that cursorial mammals concentrate limb muscle
      mass proximally to reduce energy costs during locomotion. Although supported by
      experiments where mass is added to an individual's limbs, mammals with naturally
      occurring distally heavy limbs such as primates have similar energy costs
      compared with other mammals. This study presents a new hypothesis to explain how
      animals with distally heavy limbs maintain low energy costs. Since distal mass
      should increase energy costs due to higher amounts of muscular power outputs,
      this hypothesis is based on the divergent effects of stride frequency on internal
      and external power outputs (the power output to move the limbs and the body
      center of mass, respectively). The use of low stride frequencies reduces limb
      velocities and therefore decreases internal power, while associated long strides
      increase the vertical displacement of the body center of mass and therefore
      increase external power. Total power (the sum of internal and external power) may
      therefore not differ among mammals with different limb mass distributions. To
      test this hypothesis, I examined a sample of infant baboons (Papio cynocephalus)
      during ontogeny and compared them with more cursorial mammals. Limb mass
      distribution changes with age (from distal to more proximally concentrated) in
      baboons, and the infants used shorter strides and higher stride frequencies when
      limb mass was most proximally concentrated. Compared with non-primates who have
      more proximally concentrated limb mass, the infants used longer strides and lower
      stride frequencies. Relatively low internal power was associated with low stride
      frequencies in both the intra- and inter-specific samples. However, only in the
      inter-specific comparison were relatively long strides associated with high
      external power outputs. In both the intra-specific and the inter-specific
      samples, total power did not differ between groups who differed in limb mass
      distribution. The results of this study suggest that a trade-off mechanism is
      available to quadrupeds with distally heavy limbs allowing them to maintain
      similar total power outputs (and likely similar energy costs) compared with
      mammals with more proximally concentrated limb mass.

PMID- 16449559
TI  - Effects of larval nutrition on the endocrinology of mosquito egg development.
AB  - Reproduction by female mosquitoes is dependent on energy resources but modulated
      by hormones. Our study focused on blood-meal-dependent, anautogenous Aedes
      aegypti and autogenous Ochlerotatus atropalpus that rely on larval-derived
      nutrient stores to develop eggs. To determine how larval nutrition affects the
      endocrinology of egg development in these females, we manipulated the quantity of
      larval food and measured in vitro production of juvenile hormone (JH) by corpora
      allata (CA) and ecdysteroids by ovaries. Newly emerged A. aegypti contain lower
      larval-derived protein reserves, and their CA produce high amounts of JH, in
      comparison with similarly staged Oc. atropalpus. Ecdysteroid production was
      initiated in newly emerged Oc. atropalpus females, which have higher protein
      reserves and which develop eggs without a blood meal, which is required by A.
      aegypti females to complete egg development.

PMID- 16449560
TI  - Temperature sensitivities of cytosolic malate dehydrogenases from native and
      invasive species of marine mussels (genus Mytilus): sequence-function linkages
      and correlations with biogeographic distribution.
AB  - The blue mussel Mytilus galloprovincialis, a native of the Mediterranean Sea, has
      invaded the west coast of North America in the past century, displacing the
      native blue mussel, Mytilus trossulus, from most of its former habitats in
      central and southern California. The invasive success of M. galloprovincialis is
      conjectured to be due, in part, to physiological adaptations that enable it to
      outperform M. trossulus at high temperatures. We have examined the structure and
      function of the enzyme cytosolic malate dehydrogenase (cMDH) from these species,
      as well as from the more distantly related ribbed mussel, Mytilus californianus,
      to characterize the effects of temperature on kinetic properties thought to
      exhibit thermal adaptation. The M. trossulus cMDH ortholog differs from the other
      cMDHs in a direction consistent with cold adaptation, as evidenced by a higher
      and more temperature-sensitive Michaelis-Menten constant for the cofactor NADH
      (Km(NADH)). This difference results from minor changes in sequence: the M.
      trossulus ortholog differs from the M. galloprovincialis ortholog by only two
      substitutions in the 334 amino acid monomer, and the M. californianus and M.
      trossulus orthologs differ by five substitutions. In each case, only one of these
      substitutions is non-conservative. To test the effects of individual
      substitutions on kinetic properties, we used site-directed mutagenesis to create
      recombinant cMDHs. Recombinant wild-type M. trossulus cMDH (rWT) has high
      Km(NADH) compared with mutants incorporating the non-conservative substitutions
      found in M. californianus and M. galloprovincialis - V114H and V114N,
      respectively - demonstrating that these mutations are responsible for the
      differences found in substrate affinity. Turnover number (kcat) is also higher in
      rWT compared with the two mutants, consistent with cold adaptation in the M.
      trossulus ortholog. Conversely, rWT and V114H appear more thermostable than
      V114N. Based on a comparison of Km(NADH) and kcat values among the orthologs, we
      propose that immersion temperatures are of greater selective importance in
      adapting kinetic properties than the more extreme temperatures that occur during
      emersion. The relative warm adaptation of M. galloprovincialis cMDH may be one of
      a suite of physiological characters that enhance the competitive ability of this
      invasive species in warm habitats.

PMID- 16449561
TI  - Effect of pH on the rate of myosin head detachment in molluscan catch muscle: are
      myosin heads involved in the catch state?
AB  - Moderate alkalisation is known to terminate the catch state of bivalve mollusc
      smooth muscles such as the anterior byssus retractor muscle (ABRM) of Mytilus
      edulis L. In the present study, we investigated the effect of moderate
      alkalisation (pH 7.2-7.7 vs control pH 6.7) on the myosin head detachment rate in
      saponin-skinned fibre bundles of ABRM in order to investigate the possible role
      of myosin heads in the force maintenance during catch. The detachment rate of
      myosin heads was deduced from two types of experiments. (1) In stretch
      experiments on maximally Ca2+-activated fibre bundles (pCa 4.5), the rate of
      force decay after stepwise stretch was assessed. (2) In ATP step experiments, the
      rate of force decay from high force rigor (pCa>8) was evaluated. The ATP step was
      induced by photolysis of caged ATP. We found that moderate alkalisation induces
      relaxation of skinned fibres in catch, thereby reducing both force and stiffness,
      whereas it does not accelerate the rate of myosin head detachment. This
      acceleration, however, would be expected if catch would be simply due to myosin
      heads remaining sustainably attached to actin filaments. Thus, the myosin heads
      may be less involved in catch than generally assumed. Catch may possibly depend
      on a different kind of myofilament interconnections, which are abolished by
      moderate alkalisation.

PMID- 16449562
TI  - Suppression of Na+/K+-ATPase activity during estivation in the land snail Otala
      lactea.
AB  - Entry into the hypometabolic state of estivation requires a coordinated
      suppression of the rate of cellular ATP turnover, including both ATP-generating
      and ATP-consuming reactions. As one of the largest consumers of cellular ATP, the
      plasma membrane Na+/K+-ATPase is a potentially key target for regulation during
      estivation. Na+/K+-ATPase was investigated in foot muscle and hepatopancreas of
      the land snail Otala lactea, comparing active and estivating states. In both
      tissues enzyme properties changed significantly during estivation: maximal
      activity was reduced by about one-third, affinity for Mg.ATP was reduced (Km was
      40% higher), and activation energy (derived from Arrhenius plots) was increased
      by approximately 45%. Foot muscle Na+/K+-ATPase from estivated snails also showed
      an 80% increase in Km Na+ and a 60% increase in Ka Mg2+ as compared with active
      snails, whereas hepatopancreas Na+/K+-ATPase showed a 70% increase in I50 K+
      during estivation. Western blotting with antibodies recognizing the alpha subunit
      of Na+/K+-ATPase showed no change in the amount of enzyme protein during
      estivation. Instead, the estivation-responsive change in Na+/K+-ATPase activity
      was linked to posttranslational modification. In vitro incubations manipulating
      endogenous kinase and phosphatase activities indicated that Na+/K+-ATPase from
      estivating snails was a high phosphate, low activity form, whereas
      dephosphorylation returned the enzyme to a high activity state characteristic of
      active snails. Treatment with protein kinases A, C or G could all mediate changes
      in enzyme properties in vitro that mimicked the effect of estivation, whereas
      treatments with protein phosphatase 1 or 2A had the opposite effect. Reversible
      phosphorylation control of Na+/K+-ATPase can provide the means of coordinating
      ATP use by this ion pump with the rates of ATP generation by catabolic pathways
      in estivating snails.

PMID- 16449563
TI  - The relationship between 3-D kinematics and gliding performance in the southern
      flying squirrel, Glaucomys volans.
AB  - Gliding is the simplest form of flight, yet relatively little is known about its
      mechanics in animals. The goal of this study was to describe the body position
      and performance of a gliding mammal and to identify correlates between kinematics
      and aerodynamic performance. To do this, I used a pair of high-speed digital
      cameras to record a portion of the middle of glides by southern flying squirrels,
      Glaucomys volans. The squirrels launched from a height of 4 m and landed on a
      vertical pole. Reflective markers were applied to anatomical landmarks and the 3
      D coordinates of these points were computed to describe the kinematics of the
      glides. From these data I estimated the lift and drag generated during the glide,
      and correlated these variables with gliding performance as measured by glide
      angle, glide speed and stability. In the majority of the glide sequences the
      squirrels accelerated in the downward direction and accelerated horizontally
      forward as they moved through the calibrated volume in the middle of the glide
      trajectory, rather than exhibiting a steady glide in which the body weight is
      balanced by the resultant aerodynamic force. Compared to human engineered
      airfoils, the angles of attack used by the squirrels were unexpectedly high,
      ranging from 35.4 degrees to 53.5 degrees , far above the angle of attack at
      which an aircraft wing would typically stall. As expected based on aerodynamic
      theory, there was a negative correlation between angle of attack and lift
      coefficient, indicating that the wings are stalled, and a positive correlation
      between angle of attack and drag coefficient. Also as expected, there was a
      negative correlation between lift-to-drag ratio and angle of attack, as
      increasing angle of attack produced both less lift and more drag. Within glides,
      there was a strong correlation between nose-down pitching rotations and limb
      movements that tended to increase the angle of attack of the wing membrane,
      suggesting that the animals actively control their pitch by moving their limbs.
      The squirrels used much steeper glide angles than those reported for other
      gliding animals, ranging from 40.4 degrees to 57.4 degrees . It is likely that
      this is because they did not launch from a great enough height to reach their
      minimum glide angle. In some trials the glide angle increased over the captured
      portion of the glide, whereas in others it decreased, and the magnitude of the
      changes varied substantially, rendering it difficult to ascertain which portion
      of the glide trajectory was represented. Decreases in glide angle were strongly
      correlated with increases in lift coefficient, but were uncorrelated with drag
      coefficient.

PMID- 16449564
TI  - Hagfish slime ecomechanics: testing the gill-clogging hypothesis.
AB  - Hagfish are able to produce substantial amounts of slime when harassed, but the
      precise ecological function of the slime is unclear. One possibility is that the
      slime acts as a defence against gill-breathing predators, whose gills may become
      entangled with the slime's mixture of mucins and fibrous threads during an
      attack. We previously demonstrated that hagfish slime does not bind water
      tightly, but instead behaves like a fine sieve that slows water down via viscous
      entrainment. These properties are consistent with the gill-clogging hypothesis,
      which we tested here by quantifying the effects of hagfish slime on water flow
      through an artificial gill model and real fish gills. Our results indicate that
      the slime is capable of clogging gills and increasing the resistance that they
      present to the flow of water. We also characterized the behaviour of slime
      release from live hagfish and the effect of convective mixing on the formation of
      slime in vitro. Our observations show that exudate is locally released from the
      slime glands as a coherent jet and that hagfish do not appear to use their slime
      as a protective envelope. We found that convective mixing between the exudate and
      seawater is necessary for proper slime formation, but excessive mixing leads to
      the slime's collapse. We suggest that the loose binding of water by the slime may
      be an optimal solution to the problem of delivering an expanding jet of flow
      inhibiting material to the gills of would-be predators.

PMID- 16449565
TI  - Perturbation of the activity of a single identified neuron affects long-term
      memory formation in a molluscan semi-intact preparation.
AB  - The aim of this study was to investigate the neural basis of operant conditioning
      in a semi-intact preparation of the pond snail, Lymnaea stagnalis. Lymnaea
      learns, via operant conditioning, to reduce its aerial respiratory behaviour in
      response to an aversive tactile stimulus to its open pneumostome. Here we report
      the successful conditioning of naive semi-intact preparations to show ;learning
      in the dish' and long-term memory that persists for at least 18 h. The neurons
      that generate this behaviour are readily identifiable and, for the first time, we
      have recorded from a neuron during a training paradigm that leads to long-term
      memory formation in the same preparation. Specifically, we recorded from the
      respiratory neuron Right Pedal Dorsal 1 (RPeD1), which is part of the respiratory
      central pattern generator and initiates the aerial respiratory behaviour.
      Previous studies have shown that long-term memory of this behaviour results in
      reduced RPeD1 activity. In the present study, we demonstrate that preventing
      RPeD1 impulse activity between training sessions reduces the number of sessions
      needed to produce long-term memory in our semi-intact preparation.

PMID- 16449566
TI  - Local mechanical properties of the head articulation cuticle in the beetle
      Pachnoda marginata (Coleoptera, Scarabaeidae).
AB  - Insect exoskeleton (cuticle) has a broad range of mechanical properties depending
      on the function of a particular structure of the skeleton. Structure and
      mechanical properties of the specialised cuticle of insect joints remain largely
      unknown to date. We used scanning (SEM) and transmission electron microscopy
      (TEM) to obtain information about the material structure of the gula plate, the
      head part of the head-to-neck articulation system in the beetle Pachnoda
      marginata. The surface of this cuticle appears rather smooth in SEM. The fibers
      of the exocuticle are partly oriented almost perpendicular to the surface, which
      is rather unusual for arthropod cuticle. Nanoindentation experiments were
      performed to determine the local mechanical properties (hardness and elastic
      modulus) of the gula material. To understand the effect of desiccation and the
      influence of an outer wax layer on the mechanical behavior of the material, the
      samples were tested in fresh, dry and chemically treated (lipid extraction in
      organic solvents) conditions. Nanoindentation results were found to be strongly
      influenced by desiccation but only slightly by lipid extraction. Decreasing water
      content ( approximately 15-20% of the cuticle mass) led to an increase in
      hardness (from 0.1 to 0.49 GPa) and elastic modulus (from 1.5 to 7.5 GPa). The
      lipid extraction caused a slight further hardening (to 0.52 GPa) as well as
      stiffening (to 7.7 GPa) of the material. The results are discussed in relation to
      the mechanical function of the gula plate.

PMID- 16449567
TI  - A potassium channel (Kv4) cloned from the heart of the tunicate Ciona
      intestinalis and its modulation by a KChIP subunit.
AB  - Voltage-gated ion channels of the Kv4 subfamily produce A-type currents whose
      properties are tuned by accessory subunits termed KChIPs, which are a family of
      Ca2+ sensor proteins. By modifying expression levels and the intrinsic
      biophysical properties of Kv4 channels, KChIPs modulate the excitability
      properties of neurons and myocytes. We studied how a Kv4 channel from a tunicate,
      the first branching clade of the chordates, is modulated by endogenous KChIP
      subunits. BLAST searches in the genome of Ciona intestinalis identified a single
      Kv4 gene and a single KChIP gene, implying that the diversification of both genes
      occurred during early vertebrate evolution, since the corresponding mammalian
      gene families are formed by several paralogues. In this study we describe the
      cloning and characterization of a tunicate Kv4 channel, CionaKv4, and a tunicate
      KChIP subunit, CionaKChIP. We demonstrate that CionaKChIP strongly modulates
      CionaKv4 by producing larger currents that inactivate more slowly than in the
      absence of the KChIP subunit. Furthermore, CionaKChIP shifted the midpoints of
      activation and inactivation and slowed deactivation and recovery from
      inactivation of CionaKv4. Modulation by CionaKChIP requires the presence of the
      intact N terminus of CionaKv4 because, except for a minor effect on inactivation,
      CionaKChIP did not modulate CionaKv4 channels that lacked amino acids 2-32. In
      summary, our results suggest that modulation of Kv4 channels by KChIP subunits is
      an ancient mechanism for modulating electrical excitability.

PMID- 16449568
TI  - Anatomically diverse butterfly scales all produce structural colours by coherent
      scattering.
AB  - The structural colours of butterflies and moths (Lepidoptera) have been
      attributed to a diversity of physical mechanisms, including multilayer
      interference, diffraction, Bragg scattering, Tyndall scattering and Rayleigh
      scattering. We used fibre optic spectrophotometry, transmission electron
      microscopy (TEM) and 2D Fourier analysis to investigate the physical mechanisms
      of structural colour production in twelve lepidopteran species from four
      families, representing all of the previously proposed anatomical and optical
      classes of butterfly nanostructure. The 2D Fourier analyses of TEMs of colour
      producing butterfly scales document that all species are appropriately
      nanostructured to produce visible colours by coherent scattering, i.e.
      differential interference and reinforcement of scattered, visible wavelengths.
      Previously hypothesized to produce a blue colour by incoherent, Tyndall
      scattering, the scales of Papilio zalmoxis are not appropriately nanostructured
      for incoherent scattering. Rather, available data indicate that the blue of P.
      zalmoxis is a fluorescent pigmentary colour. Despite their nanoscale anatomical
      diversity, all structurally coloured butterfly scales share a single fundamental
      physical color production mechanism - coherent scattering. Recognition of this
      commonality provides a new perspective on how the nanostructure and optical
      properties of structurally coloured butterfly scales evolved and diversified
      among and within lepidopteran clades.

PMID- 16449569
TI  - Classical conditioning of activities of salivary neurones in the cockroach.
AB  - Secretion of saliva to aid swallowing and digestion is a basic physiological
      function found in many vertebrates and invertebrates. For mammals, classical
      conditioning of salivation in dogs was reported by Pavlov a century ago. However,
      conditioning of salivation or of related neural activities in non-mammalian
      species has not been reported. In many species of insects, salivation is
      regulated by salivary neurones. In this study, we found that salivary neurones of
      the cockroach Periplaneta americana exhibited a strong response to sucrose
      solution applied to the mouth and a weak response to odours applied to an
      antenna, and we studied the effect of conditioning on the activities of salivary
      neurones. After three sets of differential conditioning trials in which an odour
      was presented just before the presentation of sucrose solution and the other
      odour was presented alone, the response of salivary neurones to sucrose
      associated odour significantly increased but that to the odour presented alone
      was unchanged. Backward pairing trials in which an odour was presented after the
      presentation of sucrose solution were not effective in achieving conditioning.
      Our study of the change in the level of saliva secretion in response to
      electrical stimulation of salivary neurones suggested that the magnitude of
      increase in odour response of salivary neurones by conditioning is sufficient to
      lead to an increased level of salivation. This study suggests classical
      conditioning of salivation in an insect.

PMID- 16449570
TI  - Target hub proteins serve as master regulators of development in yeast.
AB  - To understand the organization of the transcriptional networks that govern cell
      differentiation, we have investigated the transcriptional circuitry controlling
      pseudohyphal development in Saccharomyces cerevisiae. The binding targets of
      Ste12, Tec1, Sok2, Phd1, Mga1, and Flo8 were globally mapped across the yeast
      genome. The factors and their targets form a complex binding network, containing
      patterns characteristic of autoregulation, feedback and feed-forward loops, and
      cross-talk. Combinatorial binding to intergenic regions was commonly observed,
      which allowed for the identification of a novel binding association between Mga1
      and Flo8, in which Mga1 requires Flo8 for binding to promoter regions. Further
      analysis of the network showed that the promoters of MGA1 and PHD1 were bound by
      all of the factors used in this study, identifying them as key target hubs.
      Overexpression of either of these two proteins specifically induced pseudohyphal
      growth under noninducing conditions, highlighting them as master regulators of
      the system. Our results indicate that target hubs can serve as master regulators
      whose activity is sufficient for the induction of complex developmental responses
      and therefore represent important regulatory nodes in biological networks.

PMID- 16449571
TI  - Mammalian sperm translate nuclear-encoded proteins by mitochondrial-type
      ribosomes.
AB  - It is widely accepted that spermatozoa are translationally silent. The present
      study demonstrates, for the first time, incorporation of labeled amino acids into
      polypeptides during sperm capacitation, which was completely inhibited by
      mitochondrial translation inhibitors but not by the cytoplasmic translation
      inhibitor. Unlike 80S cytoplasmic ribosomes, 55S mitochondrial ribosomes were
      present in polysomal fractions, indicating that these ribosomes are actively
      involved in protein translation in spermatozoa. Inhibition of protein translation
      significantly reduced sperm motility, capacitation and in vitro fertilization
      rate. Thus, contrary to the accepted dogma, nuclear genes are expressed as
      proteins in sperm during their residence in the female reproductive tract until
      fertilization.

PMID- 16449572
TI  - Systems thinking and modeling for public health practice.

PMID- 16449573
TI  - HIV prevention case management is not cost-effective.

PMID- 16449574
TI  - Using adjusted relative risks to calculate attributable fractions.

PMID- 16449575
TI  - Collection of legal status information: caution!

PMID- 16449576
TI  - Policy and programmatic importance of spatial alignment of data sources.
AB  - Geographic information systems have proven instrumental in assessing
      environmental impacts on individual and community health, but numerous
      methodological challenges are associated with analyses of highly localized
      phenomena in which spatially misaligned data are used. In a case study based on
      child care facility and traffic data for the Los Angeles metropolitan area, we
      assessed the extent of facility misclassification with spatially unreconciled
      data from 3 different governmental agencies in an attempt to identify child care
      centers in which young children are at risk from high concentrations of toxic
      vehicle-exhaust pollutants. Relative to geographically corrected data,
      unreconciled information produced a modest bias in terms of aggregated number of
      facilities at risk and a substantial number of false positives and negatives.

PMID- 16449577
TI  - Systemic intervention for public health.
AB  - Many calls have been made for a systems approach to public health. My response is
      to offer a methodology for systemic intervention that (1) emphasizes the need to
      explore stakeholder values and boundaries for analysis, (2) challenges
      marginalization, and (3) draws upon a wide range of methods (from the systems
      literature and beyond) to create a flexible and responsive systems practice.I
      present and discuss several well-tested methods with a view to identifying their
      potential for supporting systemic intervention for public health.

PMID- 16449578
TI  - HIV/AIDS and other infectious diseases among correctional inmates: transmission,
      burden, and an appropriate response.
AB  - Correctional inmates engage in drug-related and sexual risk behaviors, and the
      transmission of HIV, hepatitis, and sexually transmitted diseases occurs in
      correctional facilities. However, there is uncertainty about the extent of
      transmission, and hyperbolic descriptions of its extent may further stigmatize
      inmates and elicit punitive responses. Whether infection was acquired within or
      outside correctional facilities, the prevalence of HIV and other infectious
      diseases is much higher among inmates than among those in the general community,
      and the burden of disease among inmates and releasees is disproportionately
      heavy. A comprehensive response is needed, including voluntary counseling and
      testing on request that is linked to high-quality treatment, disease prevention
      education, substance abuse treatment, and discharge planning and transitional
      programs for releasees.

PMID- 16449579
TI  - Learning from evidence in a complex world.
AB  - Policies to promote public health and welfare often fail or worsen the problems
      they are intended to solve. Evidence-based learning should prevent such policy
      resistance, but learning in complex systems is often weak and slow. Complexity
      hinders our ability to discover the delayed and distal impacts of interventions,
      generating unintended "side effects." Yet learning often fails even when strong
      evidence is available: common mental models lead to erroneous but self-confirming
      inferences, allowing harmful beliefs and behaviors to persist and undermining
      implementation of beneficial policies. Here I show how systems thinking and
      simulation modeling can help expand the boundaries of our mental models, enhance
      our ability to generate and learn from evidence, and catalyze effective change in
      public health and beyond.

PMID- 16449580
TI  - Public health asks of systems science: to advance our evidence-based practice,
      can you help us get more practice-based evidence?
AB  - Public health asks of systems science, as it did of sociology 40 years ago, that
      it help us unravel the complexity of causal forces in our varied populations and
      the ecologically layered community and societal circumstances of public health
      practice. We seek a more evidence-based public health practice, but too much of
      our evidence comes from artificially controlled research that does not fit the
      realities of practice. What can we learn from our experience with sociology in
      the past that might guide us in drawing effectively on systems science?

PMID- 16449581
TI  - Practical challenges of systems thinking and modeling in public health.
AB  - OBJECTIVES: Awareness of and support for systems thinking and modeling in the
      public health field are growing, yet there are many practical challenges to
      implementation. We sought to identify and describe these challenges from the
      perspectives of practicing public health professionals. METHODS: A systems-based
      methodology, concept mapping, was used in a study of 133 participants from 2
      systems-based public health initiatives (the Initiative for the Study and
      Implementation of Systems and the Syndemics Prevention Network). This method
      identified 100 key challenges to implementation of systems thinking and modeling
      in public health work. RESULTS: The project resulted in a map identifying 8
      categories of challenges and the dynamic interactions among them. CONCLUSIONS:
      Implementation by public health professionals of the 8 simple rules we derived
      from the clusters in the map identified here will help to address challenges and
      improve the organization of systems that protect the public's health.

PMID- 16449582
TI  - Toward ethical review of health system transformations.
AB  - Efforts to transform health systems constitute social experiments on a
      population. Like clinical research, they deploy measures that are unproven in the
      context of the reform, and they often impose significant risks on some people in
      order to achieve a social goal: the improvement of health delivery. The rationale
      for proactively evaluating clinical experimentation on human subjects also
      applies to these social experiments. We used the "benchmarks of fairness"
      methodology to illustrate the elements such an evidence-based review should
      encompass, leaving open the question of who should perform it. The review must
      include the ethical objectives of reform, namely, an integrated approach to
      equity, accountability, and efficiency; the fit between measures taken and these
      objectives; and the governance of the reform.

PMID- 16449583
TI  - Improving the effectiveness of health care and public health: a multiscale
      complex systems analysis.
AB  - The US health care system is struggling with a mismatch between the large, simple
      (low-information) financial flow and the complex (high-information) treatment of
      individual patients. Efforts to implement cost controls and industrial efficiency
      that are appropriate for repetitive tasks but not high-complexity tasks lead to
      poor quality of care. Multiscale complex systems analysis suggests that an
      important step toward relieving this structural problem is a separation of
      responsibility for 2 distinct types of tasks: medical care of individual patients
      and prevention/population health. These distinct tasks require qualitatively
      different organizational structures. The current use of care providers and
      organizations for both purposes leads to compromises in organizational process
      that adversely affect the ability of health care organizations to provide either
      individual or prevention/population services. Thus, the overall system can be
      dramatically improved by establishing 2 separate but linked systems with distinct
      organizational forms: (a) a high-efficiency system performing large-scale
      repetitive tasks such as screening tests, inoculations, and generic health care,
      and (b) a high-complexity system treating complex medical problems of individual
      patients.

PMID- 16449584
TI  - Institutional and economic determinants of public health system performance.
AB  - OBJECTIVES: Although a growing body of evidence demonstrates that availability
      and quality of essential public health services vary widely across communities,
      relatively little is known about the factors that give rise to these variations.
      We examined the association of institutional, financial, and community
      characteristics of local public health delivery systems and the performance of
      essential services. METHODS: Performance measures were collected from local
      public health systems in 7 states and combined with secondary data sources.
      Multivariate, linear, and nonlinear regression models were used to estimate
      associations between system characteristics and the performance of essential
      services. RESULTS: Performance varied significantly with the size, financial
      resources, and organizational structure of local public health systems, with some
      public health services appearing more sensitive to these characteristics than
      others. Staffing levels and community characteristics also appeared to be related
      to the performance of selected services. CONCLUSIONS: Reconfiguring the
      organization and financing of public health systems in some communities-such as
      through consolidation and enhanced intergovernmental coordination-may hold
      promise for improving the performance of essential services.

PMID- 16449586
TI  - Complex causal process diagrams for analyzing the health impacts of policy
      interventions.
AB  - Causal diagrams are rigorous tools for controlling confounding. They also can be
      used to describe complex causal systems, which is done routinely in communicable
      disease epidemiology. The use of change diagrams has advantages over static
      diagrams, because change diagrams are more tractable, relate better to
      interventions, and have clearer interpretations. Causal diagrams are a useful
      basis for modeling. They make assumptions explicit, provide a framework for
      analysis, generate testable predictions, explore the effects of interventions,
      and identify data gaps. Causal diagrams can be used to integrate different types
      of information and to facilitate communication both among public health experts
      and between public health experts and experts in other fields. Causal diagrams
      allow the use of instrumental variables, which can help control confounding and
      reverse causation.

PMID- 16449585
TI  - Simulation modeling and tobacco control: creating more robust public health
      policies.
AB  - Although previous empirical studies have shown that tobacco control policies are
      effective at reducing smoking rates, such studies have proven of limited
      effectiveness in distinguishing how the effect of policies depend on the other
      policies in place, the length of adjustment period, the way the policy is
      implemented, and the demographic groups considered. An alternative and
      complementary approach to purely statistical equations is simulation models. We
      describe the SimSmoke simulation model and how we used it to assess tobacco
      control policy in a specific case study. Simulation models are not only useful
      for policy prediction and planning but also may help to broaden our understanding
      of the role of different public health policies within a complex, dynamic social
      system.

PMID- 16449587
TI  - Understanding diabetes population dynamics through simulation modeling and
      experimentation.
AB  - Health planners in the Division of Diabetes Translation and others from the
      National Center for Chronic Disease Prevention and Health Promotion of the
      Centers for Disease Control and Prevention used system dynamics simulation
      modeling to gain a better understanding of diabetes population dynamics and to
      explore implications for public health strategy. A model was developed to explain
      the growth of diabetes since 1980 and portray possible futures through 2050. The
      model simulations suggest characteristic dynamics of the diabetes population,
      including unintended increases in diabetes prevalence due to diabetes control,
      the inability of diabetes control efforts alone to reduce diabetes-related deaths
      in the long term, and significant delays between primary prevention efforts and
      downstream improvements in diabetes outcomes.

PMID- 16449588
TI  - The impact of New York City's 1975 fiscal crisis on the tuberculosis, HIV, and
      homicide syndemic.
AB  - In 1975, New York City experienced a fiscal crisis rooted in long-term political
      and economic changes in the city. Budget and policy decisions designed to
      alleviate this fiscal crisis contributed to the subsequent epidemics of
      tuberculosis, human immunodeficiency virus (HIV) infection, and homicide in New
      York City. Because these conditions share underlying social determinants, we
      consider them a syndemic, i.e., all 3 combined to create an excess disease burden
      on the population. Cuts in services; the dismantling of health, public safety,
      and social service infrastructures; and the deterioration of living conditions
      for vulnerable populations contributed to the amplification of these health
      conditions over 2 decades. We estimate that the costs incurred in controlling
      these epidemics exceeded 50 billion US dollars (in 2004 dollars); in contrast,
      the overall budgetary saving during the fiscal crisis was 10 billion US dollars.
      This history has implications for public health professionals who must respond to
      current perceptions of local fiscal crises.

PMID- 16449589
TI  - A societal outcomes map for health research and policy.
AB  - The linkages between decisions about health research and policy and actual health
      outcomes may be extraordinarily difficult to specify. We performed a pilot
      application of a "road mapping" and technology assessment technique to perinatal
      health to illustrate how this technique can clarify the relations between
      available options and improved health outcomes. We used a combination of data
      mining techniques and qualitative analyses to set up the underlying structure of
      a societal health outcomes road map. Societal health outcomes road mapping may be
      a useful tool for enhancing the ability of the public health community,
      policymakers, and other stakeholders, such as research administrators, to
      understand health research and policy options.

PMID- 16449590
TI  - A system for rapidly and accurately collecting patients' race and ethnicity.
AB  - OBJECTIVES: We assessed the feasibility of collecting race/ethnicity data from
      patients using their own preferred racial/ethnic terms. METHODS: The 424 patients
      described their race/ethnicity using their own categories, and we compared their
      descriptions with their responses to the questions (1) "Do you consider yourself
      Latino or Hispanic?" and (2) "Which category best describes your race?" (7
      response options in our computer interview). We also determined patients'
      preferences between the 2 approaches. RESULTS: The proportions of patients who
      described themselves with 1, 2, 3, or 4 terms were 46%, 33%, 14%, and 6%,
      respectively; 2 said only "American" (1%,) and 1 refused to answer (0.5%). The
      average completion time was 37 +/- 17 seconds. Rates of missing values and
      categorization as "other" race were lower than with the closed questions.
      Agreement between racial/ethnic categorization with open-ended and closed
      responses was 93% (kappa =0.88). Latino/Hispanic and multiracial/multiethnic
      individuals were more likely to prefer using their own categories to describe
      their race/ethnicity. CONCLUSIONS: Collecting race/ethnicity data using patients'
      own racial/ethnic categories is feasible with the use of computerized systems to
      capture verbatim responses and results in lower rates of missing and unusable
      data than do standard questions.

PMID- 16449591
TI  - System dynamics modeling for public health: background and opportunities.
AB  - The systems modeling methodology of system dynamics is well suited to address the
      dynamic complexity that characterizes many public health issues. The system
      dynamics approach involves the development of computer simulation models that
      portray processes of accumulation and feedback and that may be tested
      systematically to find effective policies for overcoming policy resistance.
      System dynamics modeling of chronic disease prevention should seek to incorporate
      all the basic elements of a modern ecological approach, including disease
      outcomes, health and risk behaviors, environmental factors, and health-related
      resources and delivery systems. System dynamics shows promise as a means of
      modeling multiple interacting diseases and risks, the interaction of delivery
      systems and diseased populations, and matters of national and state policy.

PMID- 16449593
TI  - Vulnerability, human rights, and comprehensive health care needs of young people
      living with HIV/AIDS.
AB  - We sought to identify and understand the health care needs of young people living
      with HIV/AIDS, particularly in terms of their psychosocial well-being. We
      conducted a qualitative analysis of HIV-positive young people and their
      caregivers, focusing on the implications of an HIV diagnosis for health care
      needs. Stigma was a recurrent issue that arose in the interviews conducted with
      the respondents, and it was evident that youths had been denied many rights
      related to health. We concluded that young people living with HIV need
      comprehensive care based on a human rights approach. In this regard, we offer
      some practical recommendations for health programs.

PMID- 16449592
TI  - Systems analysis of real-world obstacles to successful cervical cancer prevention
      in developing countries.
AB  - Papanicolaou screening is feasible anywhere that screening for cervical cancer,
      the leading cause of cancer-related death among women in developing countries, is
      appropriate. After documenting that the Vietnam War had contributed to the
      problem of cervical cancer in Vietnam, we participated in a grass roots effort to
      establish a nationwide cervical cancer prevention program in that country and
      performed root cause analyses of program deficiencies. We found that real-world
      obstacles to successful cervical cancer prevention in developing countries
      involve people far more than technology and that such obstacles can be
      appropriately managed through a systems approach focused on programmatic quality
      rather than through ideological commitments to technology. A focus on quality
      satisfies public health goals, whereas a focus on technology is compatible with
      market forces.

PMID- 16449595
TI  - Challenges to research in urban community health centers.
AB  - Community health centers (CHCs) are important settings for research aimed at
      reducing health disparities. However, CHCs pose many challenges to research at
      patient, provider, and system levels. We summarized lessons learned from a
      multimethod, formative study to develop intervention strategies for improving
      colorectal cancer screening in CHCs, and make recommendations for future
      research. The call for research in "real world" settings such as CHCs must be
      matched with greater understanding of the challenges, as well as the resources to
      meet those challenges.

PMID- 16449594
TI  - Helping public sector health systems innovate: the strategic approach to
      strengthening reproductive health policies and programs.
AB  - Public sector health systems that provide services to poor and marginalized
      populations in developing countries face great challenges. Change associated with
      health sector reform and structural adjustment often leaves these already
      strained institutions with fewer resources and insufficient capacity to relieve
      health burdens. The Strategic Approach to Strengthening Reproductive Health
      Policies and Programs is a methodological innovation developed by the World
      Health Organization and its partners to help countries identify and prioritize
      their reproductive health service needs, test appropriate interventions, and
      scale up successful innovations to a subnational or national level. The
      participatory, interdisciplinary, and country-owned process can set in motion
      much-needed change. We describe key features of this approach, provide
      illustrations from country experiences, and use insights from the diffusion of
      innovation literature to explain the approach's dissemination and sustainability.

PMID- 16449596
TI  - Public health lessons learned from analysis of New York City subway injuries.
AB  - Serious subway injuries are devastating to their young victims and have high
      rates of mortality and amputation. We identified the urban population at greatest
      risk for subway injuries and investigated the influence of local economies on
      injury rates. We propose using changes in social conditions as a "trigger" for
      increased vigilance and protective measures at times of higher risk.

PMID- 16449597
TI  - Stigmatization of newly emerging infectious diseases: AIDS and SARS.
AB  - OBJECTIVES: We assessed relationships between sociodemographic characteristics
      and mental health status and knowledge of, being worried about, and
      stigmatization of 2 emerging infectious diseases: AIDS and SARS. METHODS: We
      conducted a random-digit-dialed survey of 928 residents of the New York City
      metropolitan area as part of a study of the effects of the September 11, 2001,
      terrorist attacks. Questions added for this study concerned respondents'
      knowledge of, worry about, and support of stigmatizing actions to control AIDS
      and SARS. RESULTS: In general, respondents with greater personal resources
      (income, education, social support) and better mental health status had more
      knowledge, were less worried, and were less likely to stigmatize. This pattern
      held for both AIDS and SARS. CONCLUSIONS: Personal resources and mental health
      factors are likely to influence the public's ability to learn about, rationally
      appraise the threat of, and minimize stigmatization of emerging infectious
      diseases such as AIDS and SARS.

PMID- 16449598
TI  - Building true capacity: indigenous models for indigenous communities.
AB  - Within the past 2 decades, community capacity building and community empowerment
      have emerged as key strategies for reducing health disparities and promoting
      public health. As with other strategies and best practices, these concepts have
      been brought to indigenous (American Indian and Alaska Native) communities
      primarily by mainstream researchers and practitioners. Mainstream models and
      their resultant programs, however, often have limited application in meeting the
      needs and realities of indigenous populations. Tribes are increasingly taking
      control of their local health care services. It is time for indigenous people not
      only to develop tribal programs but also to define and integrate the underlying
      theoretical and cultural frameworks for public health application.

PMID- 16449599
TI  - Life-course socioeconomic position and obesity in African American Women: the
      Pitt County Study.
AB  - OBJECTIVES: We studied obesity in African American women in relationship to their
      socioeconomic position (SEP) in childhood and adulthood. METHODS: On the basis of
      parents' occupation, we classified 679 women in the Pitt County (North Carolina)
      Study into low and high childhood SEP. Women's education, occupation, employment
      status, and home ownership were used to classify them into low and high adulthood
      SEP. Four life-course SEP categories resulted: low childhood/low adulthood, low
      childhood/high adulthood, high childhood/low adulthood, and high childhood/high
      adulthood. RESULTS: The odds of obesity were twice as high among women from low
      versus high childhood SEP backgrounds, and 25% higher among women of low versus
      high adulthood SEP. Compared to that in women of high SEP in both childhood and
      adulthood, the odds of obesity doubled for low/low SEP women, were 55% higher for
      low/high SEP women, and were comparable for high/low SEP women. CONCLUSIONS:
      Socioeconomic deprivation in childhood was a strong predictor of adulthood
      obesity in this community sample of African American women. Findings are
      consistent with both critical period and cumulative burden models of life-course
      socioeconomic deprivation and long-term risk for obesity in African American
      women.

PMID- 16449600
TI  - The formation of the emergency medical services system.
AB  - The evolution of the emergency medical services system in the United States
      accelerated rapidly between 1960 and 1973 as a result of a number of medical,
      historical, and social forces. Current emergency medical services researchers,
      policy advocates, and administrators must acknowledge these forces and their
      limitations and work to modify the system into one that provides uniformly high
      quality acute care to all patients, improves the overall public health through
      injury control and disease prevention programs, participates as a full partner in
      disease surveillance, and is prepared to address new community needs of all
      types.

PMID- 16449601
TI  - Public health systems research: setting a national agenda.
AB  - The Institute of Medicine has recommended that policy decisions about improvement
      of national public health systems be guided by sound scientific evidence.
      However, to date there is no national research agenda to help guide public health
      systems. The Centers for Disease Control and Prevention was called upon to lead a
      collaborative consensus-based process to define key research questions and
      establish a framework to create opportunities to better coordinate, leverage, and
      identify public health resources, which are increasingly scarce. The public
      health systems research agenda that emerged from this process has 14 over-arching
      priority research themes. This national agenda should stimulate and guide
      research to meet the urgent need to improve the nation's public health systems.

PMID- 16449603
TI  - Sufficiency and stability of evidence for public health interventions using
      cumulative meta-analysis.
AB  - We propose cumulative meta-analysis as the procedure of completing a new meta
      analysis at each successive wave in a research database. Two facets of cumulative
      knowledge are considered: the first, sufficiency, refers to whether the meta
      analytic database adequately demonstrates that a public health intervention
      works. The second, stability, refers to the shifts over time in the accruing
      evidence about whether a public health intervention works. We used a hypothetical
      data set to develop the indicators of sufficiency and stability, and then applied
      them to existing, published datasets. Our discussion centers on the implications
      of the use of this procedure in evaluating public health interventions.

PMID- 16449604
TI  - The cover. Still Life With Peonies.

PMID- 16449605
TI  - Link between smoking and mental illness may lead to treatments.

PMID- 16449602
TI  - Barriers to contraceptive use in product labeling and practice guidelines.
AB  - Many contraceptives are encumbered with potentially unnecessary restrictions on
      their use. Indeed, fear of side effects, fostered by alarmist labeling, is a
      leading reason that women do not use contraceptives. In the United States,
      hormonal methods currently require a prescription, although research suggests
      that women can adequately screen themselves for contraindications, manage side
      effects, and determine an appropriate initiation date, leaving little need for
      routine direct physician involvement. Sizing, spermicidal use, and length-of-wear
      limits burden users of cervical barriers and may be unnecessary. Despite recent
      changes in the labeling of intrauterine devices, clinicians commonly restrict use
      of this method and in some countries may limit the types of providers authorized
      to insert them. Although in some cases additional research is necessary, existing
      data indicate that evidence-based demedicalization of contraceptive provision
      could reduce costs and improve access.

PMID- 16449606
TI  - New drug formulations offer hope for easing global burden of malaria.

PMID- 16449607
TI  - Pediatricians warned about student athletes' risky weight-control tactics.

PMID- 16449608
TI  - Studies explore strategies for staying sharp. Interview by Bridget M Kuehn.

PMID- 16449609
TI  - Atypical antipsychotic drugs, dementia, and risk of death.

PMID- 16449610
TI  - Atypical antipsychotic drugs, dementia, and risk of death.

PMID- 16449611
TI  - Atypical antipsychotic drugs, dementia, and risk of death.

PMID- 16449612
TI  - CT scanning for minor head injury.

PMID- 16449613
TI  - Medical issues and Ramadan.

PMID- 16449614
TI  - CT scanning for minor head injury.

PMID- 16449615
TI  - Relapse of major depression during pregnancy in women who maintain or discontinue
      antidepressant treatment.
AB  - CONTEXT: Pregnancy has historically been described as a time of emotional well
      being, providing "protection" against psychiatric disorder. However, systematic
      delineation of risk of relapse in women who maintain or discontinue
      pharmacological treatment during pregnancy is necessary. OBJECTIVE: To describe
      risk of relapse in pregnant women who discontinued antidepressant medication
      proximate to conception compared with those who maintained treatment with these
      medications. DESIGN, SETTING, AND PATIENTS: A prospective naturalistic
      investigation using longitudinal psychiatric assessments on a monthly basis
      across pregnancy; a survival analysis was conducted to determine time to relapse
      of depression during pregnancy. A total of 201 pregnant women were enrolled
      between March 1999 and April 2003 from 3 centers with specific expertise in the
      treatment of psychiatric illness during pregnancy. The cohort of women was
      recruited from (1) within the hospital clinics, (2) self-referral via
      advertisements and community outreach detailing the study, and (3) direct
      referrals from the community. Participants were considered eligible if they (1)
      had a history of major depression prior to pregnancy, (2) were less than 16
      weeks' gestation, (3) were euthymic for at least 3 months prior to their last
      menstrual period, and (4) were currently or recently (<12 weeks prior to last
      menstrual period) receiving antidepressant treatment. Of the 201 participants, 13
      miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up
      prior to completion of pregnancy, and 8 chose to discontinue participation in the
      study. MAIN OUTCOME MEASURE: Relapse of major depression defined as fulfilling
      Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition] Diagnosis (SCID) criteria. RESULTS: Among the
      201 women in the sample, 86 (43%) experienced a relapse of major depression
      during pregnancy. Among the 82 women who maintained their medication throughout
      their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who
      discontinued medication. Women who discontinued medication relapsed significantly
      more frequently over the course of their pregnancy compared with women who
      maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1;
      P<.001). CONCLUSIONS: Pregnancy is not "protective" with respect to risk of
      relapse of major depression. Women with histories of depression who are euthymic
      in the context of ongoing antidepressant therapy should be aware of the
      association of depressive relapse during pregnancy with antidepressant
      discontinuation.

PMID- 16449616
TI  - Bone marrow transplantation for severe combined immune deficiency.
AB  - CONTEXT: Bone marrow transplantation (BMT) using stem cells obtained from a
      family-related, HLA-identical donor (RID) is the optimal treatment for patients
      with severe combined immune deficiency (SCID). In the absence of an RID, HLA
      mismatched related donors (MMRDs) are often used. However, compared with RIDs,
      use of MMRDs for BMT is associated with reduced survival and inferior long-term
      immune reconstitution. Use of HLA-matched unrelated donors (MUDs) represents
      another potential alternative for BMT. OBJECTIVE: To compare outcomes and immune
      reconstitution in a large cohort of patients with SCID who received RID, MUD, or
      MMRD BMT. DESIGN, SETTING, AND PATIENTS: Retrospective study of medical records
      from 94 infants diagnosed as having SCID who received BMT between 1990 and 2004
      at 1 Canadian and 1 Italian pediatric referral center. Thirteen, 41, and 40
      patients received RID, MUD, and MMRD BMT, respectively. MAIN OUTCOME MEASURES:
      Survival and graft failure, along with incidence of graft-vs-host disease,
      infections, and other complications; immune reconstitution was assessed in
      children who survived for more than 2 years after BMT. RESULTS: Survival after
      RID BMT was highest. Twelve (92.3%) of 13 patients who received RID BMT, 33
      (80.5%) of 41 who received MUD BMT, and 21 (52.5%) of 40 patients who received
      MMRD BMT survived. Compared with MMRD BMT, survival was significantly higher with
      RID (P = .008) or with MUD (P = .03). Graft failures and need for repeat BMT were
      more common in patients receiving MMRD BMT than in those who underwent MUD BMT.
      Long-term reconstitution of a full T-cell repertoire was achieved more frequently
      following MUD BMT (94.7%) than after MMRD BMT (61.1%) (P = .02). Acute graft-vs
      host disease was documented in 73.1% of patients following MUD BMT but in only
      45% after MMRD BMT (P = .009). Conversely, interstitial pneumonitis was observed
      more frequently after MMRD BMT (14 [35.0%] of 40) than after MUD BMT (3 [7.3%] of
      41; P = .002). CONCLUSION: Our study suggests that in the absence of a relative
      with identical HLA, MUD BMT may provide better engraftment, immune
      reconstitution, and survival for patients with SCID than MMRD BMT.

PMID- 16449617
TI  - Prevalence of HIV-1 in blood donations following implementation of a structured
      blood safety policy in South Africa.
AB  - CONTEXT: The South African National Blood Service collects more than 700,000
      units of blood annually from a population in which 11.4% is infected with human
      immunodeficiency virus 1 (HIV-1). The prevalence of HIV-1 in blood donations
      increased to 0.26% (1:385) in 1998, indicating that a significant number of
      window-period infective units were entering the blood supply (risk 3.4/100,000).
      OBJECTIVES: To determine whether the implementation of a new donor selection
      policy and educational program introduced in 1999 was associated with reductions
      in the incidence and prevalence of HIV-1 in blood donations and the reduced
      transmission risk. DESIGN: We compared the prevalence of HIV-1 in 880,534 blood
      donations collected from 1999 through 2000 with the 791,639 blood donations
      collected from 2001 through 2002. We estimated the incidence of HIV-1 in 93,378
      (1999-2000) and 67,231 (2001-2002) first-time donations and the residual risk for
      all donations in 2001-2002 using the less-sensitive enzyme-linked immunoassay and
      incidence-window period model. SETTING: All blood donors in the Inland region of
      the South African National Blood Service were analyzed. INTERVENTION: Donor
      clinics in high HIV prevalence areas were closed. Programs targeting repeat
      donors and youth were initiated and HIV risk behavior education programs were
      developed. Structured donor interviews and an enhanced donor self-exclusion
      questionnaire were institutionalized. RESULTS: The prevalence of HIV-1 in blood
      donations declined from 0.17% in 1999-2000 to 0.08% in 2001-2002 after the
      implementation of the new donor selection and education policy. The number of
      high-risk donations collected decreased from 2.6% to 1.7% (P<.001), and the
      likelihood of these donations being infected decreased from 4.8% to 3.25%. The
      likelihood of first-time donors being recently infected with HIV-1 decreased from
      18% to 14% (P = .07) and respective incidence of high-risk donations collected
      decreased from 2.6% to 1.7%. Donations from the majority black population
      declined from 6.6% to 4.2% (P<.001). Analysis of HIV-1 incidence in 2001-2002
      suggests a residual risk of collecting a window period infectious unit of
      2.6/100,000. CONCLUSION: The implementation of enhanced education and selection
      policies in South Africa was associated with decreased prevalence of HIV-1 in
      blood donations.

PMID- 16449618
TI  - Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus
      erythematosus.
AB  - CONTEXT: Manifestations of systemic lupus erythematosus (SLE) may in most
      patients be ameliorated with medications that suppress the immune system.
      Nevertheless, there remains a subset of SLE patients for whom current strategies
      are insufficient to control disease. OBJECTIVE: To assess the safety of intense
      immunosuppression and autologous hematopoietic stem cell support in patients with
      severe and treatment-refractory SLE. DESIGN, SETTING, AND PARTICIPANTS: A single
      arm trial of 50 patients with SLE refractory to standard immunosuppressive
      therapies and either organ- or life-threatening visceral involvement. Patients
      were enrolled from April 1997 through January 2005 in an autologous
      nonmyeloablative hematopoietic stem cell transplantation (HSCT) study at a single
      US medical center. INTERVENTIONS: Peripheral blood stem cells were mobilized with
      cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (5
      microg/kg per day), enriched ex vivo by CD34+ immunoselection, cryopreserved, and
      reinfused after treatment with cyclophosphamide (200 mg/kg) and equine
      antithymocyte globulin (90 mg/kg). MAIN OUTCOME MEASURES: The primary end point
      was survival, both overall and disease-free. Secondary end points included SLE
      Disease Activity Index (SLEDAI), serology (antinuclear antibody [ANA] and anti
      double-stranded (ds) DNA), complement C3 and C4, and changes in renal and
      pulmonary organ function assessed before treatment and at 6 months, 12 months,
      and then yearly for 5 years. RESULTS: Fifty patients were enrolled and underwent
      stem cell mobilization. Two patients died after mobilization, one from
      disseminated mucormycosis and another from active lupus after postponing the
      transplantation for 4 months. Forty-eight patients underwent nonmyeloablative
      HSCT. Treatment-related mortality was 2% (1/50). By intention to treat, treatment
      related mortality was 4% (2/50). With a mean follow-up of 29 months (range, 6
      months to 7.5 years) for patients undergoing HSCT, overall 5-year survival was
      84%, and probability of disease-free survival at 5 years following HSCT was 50%.
      Secondary analysis demonstrated stabilization of renal function and significant
      improvement in SLEDAI score, ANA, anti-ds DNA, complement, and carbon monoxide
      diffusion lung capacity adjusted for hemoglobin. CONCLUSIONS: In treatment
      refractory SLE, autologous nonmyeloablative HSCT results in amelioration of
      disease activity, improvement in serologic markers, and either stabilization or
      reversal of organ dysfunction. These data are nonrandomized and thus preliminary,
      providing the foundation and justification for a definitive randomized trial.
      Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00271934.

PMID- 16449619
TI  - Does the clinical examination predict lower extremity peripheral arterial
      disease?
AB  - CONTEXT: Lower extremity peripheral arterial disease (PAD) is common and
      associated with significant increases in morbidity and mortality. Physicians
      typically depend on the clinical examination to identify patients who need
      further diagnostic testing. OBJECTIVE: To systematically review the accuracy and
      precision of the clinical examination for PAD. DATA SOURCES, STUDY SELECTION, AND
      DATA EXTRACTION: MEDLINE (January 1966 to March 2005) and Cochrane databases were
      searched for articles on the diagnosis of PAD based on physical examination
      published in the English language. Included studies compared an element of the
      history or physical examination with a reference standard of ankle-brachial
      index, duplex sonography, or angiogram. Seventeen of the 51 potential articles
      identified met inclusion criteria. Two of the authors independently extracted
      data, performed quality review, and used consensus to resolve any discrepancies.
      DATA SYNTHESIS: For asymptomatic patients, the most useful clinical findings to
      diagnose PAD are the presence of claudication (likelihood ratio [LR], 3.30; 95%
      confidence interval [CI], 2.30-4.80), femoral bruit (LR, 4.80; 95% CI, 2.40
      9.50), or any pulse abnormality (LR, 3.10; 95% CI, 1.40-6.60). While none of the
      clinical examination features help to lower the likelihood of any degree of PAD,
      the absence of claudication or the presence of normal pulses decreases the
      likelihood of moderate to severe disease. When considering patients who are
      symptomatic with leg complaints, the most useful clinical findings are the
      presence of cool skin (LR, 5.90; 95% CI, 4.10-8.60), the presence of at least 1
      bruit (LR, 5.60; 95% CI, 4.70-6.70), or any palpable pulse abnormality (LR, 4.70;
      95% CI, 2.20-9.90). The absence of any bruits (iliac, femoral, or popliteal) (LR,
      0.39; 95% CI, 0.34-0.45) or pulse abnormality (LR, 0.38; 95% CI, 0.23-0.64)
      reduces the likelihood of PAD. Combinations of physical examination findings do
      not increase the likelihood of PAD beyond that of individual clinical findings.
      However, when combinations of clinical findings are all normal, the likelihood of
      disease is lower than when individual symptoms or signs are normal. A PAD scoring
      system, which includes auscultation of arterial components by handheld Doppler,
      provides greater diagnostic accuracy. CONCLUSIONS: Clinical examination findings
      must be used in the context of the pretest probability because they are not
      independently sufficient to include or exclude a diagnosis of PAD with certainty.
      The PAD screening score using the hand-held Doppler has the greatest diagnostic
      accuracy.

PMID- 16449620
TI  - Medical treatment of peripheral arterial disease.
AB  - CONTEXT: Peripheral arterial disease (PAD) affects approximately 20% of adults
      older than 55 years and is a powerful predictor of myocardial infarction, stroke,
      and death due to vascular causes. The goals of treatment are to prevent future
      major coronary and cerebrovascular events and improve leg symptoms. OBJECTIVE: To
      review the best evidence for medical treatment of PAD. EVIDENCE ACQUISITION:
      MEDLINE and the Cochrane database were searched from 1990 to November 2005 for
      randomized trials and meta-analyses of medical treatments for PAD. References
      from these articles were also searched. Search terms included, singly and in
      combination: peripheral arterial disease, peripheral artery disease, PAD,
      randomized controlled trial, controlled trial, randomized, and meta-analysis.
      Particular attention was directed toward randomized controlled trials and meta
      analyses of clinically relevant medical treatments for PAD. Outcome measures
      included leg symptoms (intermittent claudication and walking distance), death,
      and major coronary and cerebrovascular events. EVIDENCE SYNTHESIS: Symptoms of
      leg claudication, walking distance, and quality of life can be improved by
      smoking cessation (physician advice, nicotine replacement therapy, and
      bupropion), a structured exercise program, statin drugs, cilostazol, and
      angiotensin-converting enzyme inhibitors. The risk of major coronary and
      cerebrovascular events can be reduced through lowering blood pressure with
      angiotensin-converting enzyme inhibitors and other antihypertensive drugs, use of
      statin drugs, antiplatelet therapy with aspirin or clopidogrel, and probably by
      stopping smoking. CONCLUSION: The substantial and increasing burden of PAD, and
      its local and systemic complications, can be reduced by lifestyle modification
      (smoking cessation, exercise) and medical therapies (nicotine replacement
      therapy, bupropion, antihypertensive drugs, statins, and antiplatelet drugs).

PMID- 16449621
TI  - Medical countermeasures for pandemic influenza: ethics and the law.

PMID- 16449622
TI  - Blood safety--at what cost?

PMID- 16449623
TI  - High-dose cyclophosphamide and stem cell transplantation for refractory systemic
      lupus erythematosus.

PMID- 16449628
TI  - JAMA patient page. Peripheral arterial disease.

PMID- 16449630
TI  - A side order of stem cells: the SP phenotype.
AB  - A defining property of murine hematopoietic stem cells (HSCs) is low fluorescence
      after staining with Hoechst 33342 and Rhodamine 123. These dyes have proven to be
      remarkably powerful tools in the purification and characterization of HSCs when
      used alone or in combination with antibodies directed against stem cell epitopes.
      Hoechst low cells are described as side population (SP) cells by virtue of their
      typical profiles in Hoechst red versus Hoechst blue bivariate fluorescent
      activated cell sorting dot plots. Recently, excitement has been generated by the
      findings that putative stem cells from solid tissues may also possess this SP
      phenotype. SP cells have now been isolated from a wide variety of mammalian
      tissues based on this same dye efflux phenomenon, and in many cases this cell
      population has been shown to contain apparently multipotent stem cells. What is
      yet to be clearly addressed is whether cell fusion accounts for this perceived SP
      multipotency. Indeed, if low fluorescence after Hoechst staining is a phenotype
      shared by hematopoietic and organ-specific stem cells, do all resident tissue SP
      cells have bone marrow origins or might the SP phenotype be a property common to
      all stem cells? Subject to further analysis, the SP phenotype may prove
      invaluable for the initial isolation of resident tissue stem cells in the absence
      of definitive cell-surface markers and may have broad-ranging applications in
      stem cell biology, from the purification of novel stem cell populations to the
      development of autologous stem cell therapies.

PMID- 16449631
TI  - The molecular perspective: c-Abl tyrosine kinase.

PMID- 16449632
TI  - Surprising dependency for retinoblastoma protein in ras-mediated tumorigenesis.

PMID- 16449633
TI  - The retinoblastoma protein is required for Ras-induced oncogenic transformation.
AB  - Most human cancers involve either mutational activation of the Ras oncogenic
      pathway and/or inactivation of the retinoblastoma tumor suppressor (RB) pathway.
      Paradoxically, tumors that harbor Ras mutations almost invariably retain
      expression of a wild-type pRB protein. We explain this phenomenon by
      demonstrating that Ras-induced oncogenic transformation surprisingly depends on
      functional pRB protein. Cells lacking pRB are less susceptible to the oncogenic
      actions of H-RasV12 than wild-type cells and activated Ras has an inhibitory
      effect on the proliferation of pRB-deficient human tumor cells. In addition,
      depletion of pRB from Ras-transformed murine cells or human tumor cells that
      harbor Ras pathway mutations inhibits their proliferation and anchorage
      independent growth. In sharp contrast to pRB-/- 3T3 cells, fibroblasts deficient
      in other pRB family members (p107 and p130) are more susceptible to Ras-mediated
      transformation than wild-type 3T3 cells. Moreover, loss of pRB in tumor cells
      harboring a Ras mutation results in increased expression of p107, and
      overexpression of p107 but not pRB strongly inhibits proliferation of these tumor
      cells. Together, these findings suggest that pRB and p107 have distinct roles in
      Ras-mediated transformation and suggest a novel tumor-suppressive role for p107
      in the context of activated Ras.

PMID- 16449634
TI  - Comprehensive mutational analysis of yeast DEXD/H box RNA helicases required for
      small ribosomal subunit synthesis.
AB  - The 17 putative RNA helicases required for pre-rRNA processing are predicted to
      play a crucial role in ribosome biogenesis by driving structural rearrangements
      within preribosomes. To better understand the function of these proteins, we have
      generated a battery of mutations in five putative RNA helicases involved in 18S
      rRNA synthesis and analyzed their effects on cell growth and pre-rRNA processing.
      Our results define functionally important residues within conserved motifs and
      demonstrate that lethal mutations in predicted ATP binding-hydrolysis motifs
      often confer a dominant negative phenotype in vivo when overexpressed in a wild
      type background. We show that dominant negative mutants delay processing of the
      35S pre-rRNA and cause accumulation of pre-rRNA species that normally have low
      steady-state levels. Our combined results establish that not all conserved
      domains function identically in each protein, suggesting that the RNA helicases
      may have distinct biochemical properties and diverse roles in ribosome
      biogenesis.

PMID- 16449635
TI  - Comprehensive mutational analysis of yeast DEXD/H box RNA helicases involved in
      large ribosomal subunit biogenesis.
AB  - DEXD/H box putative RNA helicases are required for pre-rRNA processing in
      Saccharomyces cerevisiae, although their exact roles and substrates are unknown.
      To characterize the significance of the conserved motifs for helicase function, a
      series of five mutations were created in each of the eight essential RNA
      helicases (Has1, Dbp6, Dbp10, Mak5, Mtr4, Drs1, Spb4, and Dbp9) involved in 60S
      ribosomal subunit biogenesis. Each mutant helicase was screened for the ability
      to confer dominant negative growth defects and for functional complementation.
      Different mutations showed different degrees of growth inhibition among the
      helicases, suggesting that the conserved regions do not function identically in
      vivo. Mutations in motif I and motif II (the DEXD/H box) often conferred dominant
      negative growth defects, indicating that these mutations do not interfere with
      substrate binding. In addition, mutations in the putative unwinding domains
      (motif III) demonstrated that conserved amino acids are often not essential for
      function. Northern analysis of steady-state RNA from strains expressing mutant
      helicases showed that the dominant negative mutations also altered pre-rRNA
      processing. Coimmunoprecipitation experiments indicated that some RNA helicases
      associated with each other. In addition, we found that yeasts disrupted in
      expression of the two nonessential RNA helicases, Dbp3 and Dbp7, grew worse than
      when either one alone was disrupted.

PMID- 16449636
TI  - Fox-2 mediates epithelial cell-specific fibroblast growth factor receptor 2 exon
      choice.
AB  - Alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts
      occurs in a cell-type-specific manner leading to the mutually exclusive use of
      exon IIIb in epithelia or exon IIIc in mesenchyme. Epithelial cell-specific exon
      choice is dependent on (U)GCAUG elements, which have been shown to bind Fox
      protein family members. In this paper we show that FGFR2 exon choice is regulated
      by (U)GCAUG elements and Fox protein family members. Fox-2 isoforms are
      differentially expressed in IIIb+ cells in comparison to IIIc+ cells, and
      expression of Fox-1 or Fox-2 in the latter led to a striking alteration in FGFR2
      splice choice from IIIc to IIIb. This switch was absolutely dependent on the
      (U)GCAUG elements present in the FGFR2 pre-mRNA and required critical residues in
      the C-terminal region of Fox-2. Interestingly, Fox-2 expression led to skipping
      of exon 6 among endogenous Fox-2 transcripts and formation of an inactive Fox-2
      isoform, which suggests that Fox-2 can regulate its own activity. Moreover, the
      repression of exon IIIc in IIIb+ cells was abrogated by interfering RNA-mediated
      knockdown of Fox-2. We also show that Fox-2 is critical for the FGFR2(IIIb)-to
      FGFR2(IIIc) switch observed in T Rex-293 cells grown to overconfluency.
      Overconfluent T Rex-293 cells show molecular and morphological changes consistent
      with a mesenchymal-to-epithelial transition. If overconfluent cells are depleted
      of Fox-2, the switch from IIIc to IIIb is abrogated. The data in this paper place
      Fox-2 among critical regulators of gene expression during mesenchymal-epithelial
      transitions and demonstrate that this action of Fox-2 is mediated by mechanisms
      distinct from those described for other cases of Fox activity.

PMID- 16449637
TI  - Cyclic AMP inhibits p38 activation via CREB-induced dynein light chain.
AB  - The mitogen-activated protein kinase p38 plays a critical role in inflammation,
      cell cycle progression, differentiation, and apoptosis. The activity of p38 is
      stimulated by a variety of extracellular stimuli, such as the proinflammatory
      cytokine tumor necrosis factor alpha (TNF-alpha), and subjected to regulation by
      other intracellular signaling pathways, including the cyclic AMP (cAMP) pathway.
      Yet the underlying mechanism by which cAMP inhibits p38 activation is unknown.
      Here we show that the induction of dynein light chain (DLC) by cAMP response
      element-binding protein (CREB) is required for cAMP-mediated inhibition of p38
      activation. cAMP inhibits p38 activation via the protein kinase A-CREB pathway.
      The inhibition is mediated by the CREB target gene Dlc, whose protein product,
      DLC, interferes with the formation of the MKK3/6-p38 complex, thereby suppressing
      p38 phosphorylation activation by MKK3/6. The inhibition of p38 activation by
      cAMP leads to suppression of NF-kappaB activity and promotion of apoptosis in
      response to TNF-alpha. Thus, our results identify DLC as a novel inhibitor of the
      p38 pathway and provide a molecular mechanism by which cAMP suppresses p38
      activation and promotes apoptosis.

PMID- 16449638
TI  - CAND1-mediated substrate adaptor recycling is required for efficient repression
      of Nrf2 by Keap1.
AB  - The bZIP transcription factor Nrf2 controls a genetic program that protects cells
      from oxidative damage and maintains cellular redox homeostasis. Keap1, a BTB
      Kelch protein, is the major upstream regulator of Nrf2. Keap1 functions as a
      substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex to
      repress steady-state levels of Nrf2 and Nrf2-dependent transcription. Cullin
      dependent ubiquitin ligase complexes have been proposed to undergo dynamic cycles
      of assembly and disassembly that enable substrate adaptor exchange or recycling.
      In this report, we have characterized the importance of substrate adaptor
      recycling for regulation of Keap1-mediated repression of Nrf2. Association of
      Keap1 with Cul3 was decreased by ectopic expression of CAND1 and was increased by
      small interfering RNA (siRNA)-mediated knockdown of CAND1. However, both ectopic
      overexpression and siRNA-mediated knockdown of CAND1 decreased the ability of
      Keap1 to target Nrf2 for ubiquitin-dependent degradation, resulting in
      stabilization of Nrf2 and activation of Nrf2-dependent gene expression.
      Neddylation of Cul3 on Lys 712 is required for Keap1-dependent ubiquitination of
      Nrf2 in vivo. However, the K712R mutant Cul3 molecule, which is not neddylated,
      can still assemble with Keap1 into a functional ubiquitin ligase complex in
      vitro. These results provide support for a model in which substrate adaptor
      recycling is required for efficient substrate ubiquitination by cullin-dependent
      E3 ubiquitin ligase complexes.

PMID- 16449639
TI  - Developmental profile of H19 differentially methylated domain (DMD) deletion
      alleles reveals multiple roles of the DMD in regulating allelic expression and
      DNA methylation at the imprinted H19/Igf2 locus.
AB  - The differentially methylated domain (DMD) of the mouse H19 gene is a methylation
      sensitive insulator that blocks access of the Igf2 gene to shared enhancers on
      the maternal allele and inactivates H19 expression on the methylated paternal
      allele. By analyzing H19 DMD deletion alleles H19DeltaDMD and H19Delta3.8kb-5'H19
      in pre- and postimplantation embryos, we show that the DMD exhibits positive
      transcriptional activity and is required for H19 expression in blastocysts and
      full activation of H19 during subsequent development. We also show that the DMD
      is required to establish Igf2 imprinting by blocking access to shared enhancers
      when Igf2 monoallelic expression is initiated in postimplantation embryos and
      that the single remaining CTCF site of the H19DeltaDMD allele is unable to
      provide this function. Furthermore, our data demonstrate that sequence outside of
      the DMD can attract some paternal-allele-specific CpG methylation 5' of H19 in
      preimplantation embryos, although this methylation is not maintained during
      postimplantation in the absence of the DMD. Finally, we report a conditional
      allele floxing the 1.6-kb sequence deleted from the H19DeltaDMD allele and
      demonstrate that the DMD is required to maintain repression of the maternal Igf2
      allele and the full activity of the paternal Igf2 allele in neonatal liver.

PMID- 16449640
TI  - Chromatin decondensation and nuclear reprogramming by nucleoplasmin.
AB  - Somatic cell nuclear cloning has repeatedly demonstrated striking reversibility
      of epigenetic regulation of cell differentiation. Upon injection into eggs, the
      donor nuclei exhibit global chromatin decondensation, which might contribute to
      reprogramming the nuclei by derepressing dormant genes. Decondensation of sperm
      chromatin in eggs is explained by the replacement of sperm-specific histone
      variants with egg-type histones by the egg protein nucleoplasmin (Npm). However,
      little is known about the mechanisms of chromatin decondensation in somatic
      nuclei that do not contain condensation-specific histone variants. Here we found
      that Npm could widely decondense chromatin in undifferentiated mouse cells
      without overt histone exchanges but with specific epigenetic modifications that
      are relevant to open chromatin structure. These modifications included nucleus
      wide multiple histone H3 phosphorylation, acetylation of Lys 14 in histone H3,
      and release of heterochromatin proteins HP1beta and TIF1beta from the nuclei. The
      protein kinase inhibitor staurosporine inhibited chromatin decondensation and
      these epigenetic modifications with the exception of H3 acetylation, potentially
      linking these chromatin events. At the functional level, Npm pretreatment of
      mouse nuclei facilitated activation of four oocyte-specific genes from the nuclei
      injected into Xenopus laevis oocytes. Future molecular elucidation of chromatin
      decondensation by Npm will significantly contribute to our understanding of the
      plasticity of cell differentiation.

PMID- 16449641
TI  - hUPF2 silencing identifies physiologic substrates of mammalian nonsense-mediated
      mRNA decay.
AB  - Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway
      that selectively degrades aberrant mRNAs with premature termination codons
      (PTCs). Although a small number of cases exist in mammals, where NMD controls
      levels of physiologic PTC transcripts, it is still unclear whether the engagement
      of NMD in posttranscriptional control of gene expression is a more prevalent
      phenomenon. To identify physiologic NMD substrates and to study how NMD silencing
      affects the overall dynamics of a cell, we stably down-regulated hUPF2, the human
      homolog of the yeast NMD factor UPF2, by RNA interference. As expected, hUPF2
      silenced HeLa cells were impaired in their ability to recognize ectopically
      expressed aberrant PTC transcripts. Surprisingly, hUPF2 silencing did not affect
      cell growth and viability but clearly diminished phosphorylation of hUPF1,
      suggesting a role of hUPF2 in modulating NMD activity through phosphorylation of
      hUPF1. Genome-wide DNA microarray expression profiling identified 37 novel up
      regulated and 57 down-regulated transcripts in hUPF2-silenced cells. About 60% of
      the up-regulated mRNAs carry typical NMD motifs. Hence, NMD is important not only
      for maintaining the transcriptome integrity by removing nonfunctional and
      aberrant PTC-bearing transcripts but also for posttranscriptional control of
      selected physiologic transcripts with NMD features.

PMID- 16449642
TI  - Recruitment of the histone methyltransferase SUV39H1 and its role in the
      oncogenic properties of the leukemia-associated PML-retinoic acid receptor fusion
      protein.
AB  - Leukemia-associated fusion proteins establish aberrant transcriptional programs,
      which result in the block of hematopoietic differentiation, a prominent feature
      of the leukemic phenotype. The dissection of the mechanisms of deregulated
      transcription by leukemia fusion proteins is therefore critical for the design of
      tailored antileukemic strategies, aimed at reestablishing the differentiation
      program of leukemic cells. The acute promyelocytic leukemia (APL)-associated
      fusion protein PML-retinoic acid receptor (RAR) behaves as an aberrant
      transcriptional repressor, due to its ability to induce chromatin modifications
      (histone deacetylation and DNA methylation) and silencing of PML-RAR target
      genes. Here, we indicate that the ultimate result of PML-RAR action is to impose
      a heterochromatin-like structure on its target genes, thereby establishing a
      permanent transcriptional silencing. This effect is mediated by the previously
      described association of PML-RAR with chromatin-modifying enzymes (histone
      deacetylases and DNA methyltransferases) and by recruitment of the histone
      methyltransferase SUV39H1, responsible for trimethylation of lysine 9 of histone
      H3.

PMID- 16449643
TI  - Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase
      kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion.
AB  - Programmed cell death 4 (Pdcd4) suppresses neoplastic transformation by
      inhibiting the activation of c-Jun and consequently AP-1-dependent transcription.
      We report that Pdcd4 blocks c-Jun activation by inhibiting the expression of
      mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1)/hematopoietic
      progenitor kinase 1, a kinase upstream of Jun N-terminal kinase (JNK). cDNA
      microarray analysis of Pdcd4-overexpressing RKO human colon carcinoma cells
      revealed MAP4K1 as the sole target of Pdcd4 on the JNK activation pathway.
      Cotransfection of a MAP4K1 promoter-reporter with Pdcd4 demonstrated inhibition
      of transcription from the MAP4K1 promoter. Ectopic expression of Pdcd4 in
      metastatic RKO cells suppressed invasion. MAP4K1 activity is functionally
      significant in invasion, as overexpression of a dominant negative MAP4K1
      (dnMAP4K1) mutant in RKO cells inhibited not only c-Jun activation but also
      invasion. Overexpression of a MAP4K1 cDNA in Pdcd4-transfected cells rescued the
      kinase activity of JNK. Thus, Pdcd4 suppresses tumor progression in human colon
      carcinoma cells by the novel mechanism of down-regulating MAP4K1 transcription,
      with consequent inhibition of c-Jun activation and AP-1-dependent transcription.

PMID- 16449644
TI  - Selective repression of low-density lipoprotein receptor expression by SP600125:
      coupling of histone H3-Ser10 phosphorylation and Sp1 occupancy.
AB  - In this study, we show that exposure of human hepatocellular HepG2 cells to
      SP600125 rapidly and dramatically reduced global histone H3-Ser10
      phosphorylation, without significantly affecting the global acetylation of
      neighboring lysines. The loss of phosphorylation is not due to changes in cell
      cycle distribution and/or apoptosis and is mediated independent of either
      p46/54(JNK) or MSK-1/2 inhibition. Moreover, SP600125 repressed the basal
      expression of the endogenous LDL receptor in a gene-specific manner, whereas the
      expression of squalene synthase, sterol response element-binding protein-1, and
      beta-actin was not altered by SP600125. Finally, chromatin immunoprecipitation
      and in vivo footprinting assays provided direct evidence that localized histone
      H3-Ser10 dephosphorylation at the low-density lipoprotein receptor promoter was
      associated with a significant decrease in the occupancy of the Sp1 binding site,
      with a slight reduction in the occupancy of RNA polymerase II. Together, our
      findings show that SP600125 is an efficient inhibitor of histone H3-Ser10
      phosphorylation in vivo, and our results led us to hypothesize that this
      modification plays a novel role in regulating transcriptional control by
      modulating promoter accessibility to maintain basal expression in a gene-specific
      manner.

PMID- 16449645
TI  - The mechanism of nuclear export of Smad3 involves exportin 4 and Ran.
AB  - Transforming growth factor beta (TGF-beta) receptors phosphorylate Smad3 and
      induce its nuclear import so it can regulate gene transcription. Smad3 can return
      to the cytoplasm to propagate further cycles of signal transduction or to be
      degraded. We demonstrate that Smad3 is exported by a constitutive mechanism that
      is insensitive to leptomycin B. The Mad homology 2 (MH2) domain is responsible
      for Smad3 export, which requires the GTPase Ran. Inactive, GDP-locked RanT24N or
      nuclear microinjection of Ran GTPase activating protein 1 blocked Smad3 export.
      Inactivation of the Ran guanine nucleotide exchange factor RCC1 inhibited Smad3
      export and led to nuclear accumulation of phosphorylated Smad3. A screen for
      importin/exportin family members that associate with Smad3 identified exportin 4,
      which binds a conserved peptide sequence in the MH2 domain of Smad3 in a Ran
      dependent manner. Exportin 4 is sufficient for carrying the in vitro nuclear
      export of Smad3 in cooperation with Ran. Knockdown of endogenous exportin 4
      completely abrogates the export of endogenous Smad3. A short peptide representing
      the minimal interaction domain in Smad3 effectively competes with Smad3
      association to exportin 4 and blocks nuclear export of Smad3 in vivo. We thus
      delineate a novel nuclear export pathway for Smad3.

PMID- 16449646
TI  - Splicing of a critical exon of human Survival Motor Neuron is regulated by a
      unique silencer element located in the last intron.
AB  - Humans have two nearly identical copies of the Survival Motor Neuron (SMN) gene,
      SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate
      for the loss of SMN1 due to exclusion of exon 7. Here we describe a novel
      inhibitory element located immediately downstream of the 5' splice site in intron
      7. We call this element intronic splicing silencer N1 (ISS-N1). Deletion of ISS
      N1 promoted exon 7 inclusion in mRNAs derived from the SMN2 minigene. Underlining
      the dominant role of ISS-N1 in exon 7 skipping, abrogation of a number of
      positive cis elements was tolerated when ISS-N1 was deleted. Confirming the
      silencer function of ISS-N1, an antisense oligonucleotide against ISS-N1 restored
      exon 7 inclusion in mRNAs derived from the SMN2 minigene or from endogenous SMN2.
      Consistently, this oligonucleotide increased the levels of SMN protein in SMA
      patient-derived cells that carry only the SMN2 gene. Our findings underscore for
      the first time the profound impact of an evolutionarily nonconserved intronic
      element on SMN2 exon 7 splicing. Considering that oligonucleotides annealing to
      intronic sequences do not interfere with exon-junction complex formation or mRNA
      transport and translation, ISS-N1 provides a very specific and efficient
      therapeutic target for antisense oligonucleotide-mediated correction of SMN2
      splicing in SMA.

PMID- 16449647
TI  - Transcriptional regulation of PEN-2, a key component of the gamma-secretase
      complex, by CREB.
AB  - Gamma-secretase, which is responsible for the intramembranous cleavage of
      Alzheimer's beta-amyloid precursor protein (APP), the signaling receptor Notch,
      and many other substrates, is a multiprotein complex consisting of at least four
      components: presenilin (PS), nicastrin, APH-1, and PEN-2. Despite the fact that
      PEN-2 is known to mediate endoproteolytic cleavage of full-length PS and APH-1
      and nicastrin are required for maintaining the stability of the complex, the
      detailed physiological function of each component remain elusive. Unlike that of
      PS, the transcriptional regulation of PEN-2, APH-1, and nicastrin has not been
      investigated. Here, we characterized the upstream regions of the human PEN-2 gene
      and identified a 238-bp fragment located 353 bp upstream of the translational
      start codon as the key region necessary for the promoter activity. Further
      analysis revealed a CREB binding site located in the 238-bp region that is
      essential for the transcriptional activity of the PEN-2 promoter. Mutation of the
      CREB site abolished the transcriptional activity of the PEN-2 promoter.
      Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis
      showed the binding of CREB to the PEN-2 promoter region both in vitro and in
      vivo. Activation of the CREB transcriptional factor by forskolin dramatically
      promoted the expression of PEN-2 mRNA and protein, whereas the other components
      of the gamma-secretase complex remained unaffected. Forskolin treatment slightly
      increases the secretion of soluble APPalpha and Abeta without affecting Notch
      cleavage. These results demonstrate that expression of PEN-2 is regulated by CREB
      and suggest that the specific control of PEN-2 expression may imply additional
      physiological functions uniquely assigned to PEN-2.

PMID- 16449648
TI  - Eukaryotic translation initiation factor 3 (eIF3) and eIF2 can promote mRNA
      binding to 40S subunits independently of eIF4G in yeast.
AB  - Recruitment of the eukaryotic translation initiation factor 2 (eIF2)-GTP-Met
      tRNAiMet ternary complex to the 40S ribosome is stimulated by multiple initiation
      factors in vitro, including eIF3, eIF1, eIF5, and eIF1A. Recruitment of mRNA is
      thought to require the functions of eIF4F and eIF3, with the latter serving as an
      adaptor between the ribosome and the 4G subunit of eIF4F. To define the factor
      requirements for these reactions in vivo, we examined the effects of depleting
      eIF2, eIF3, eIF5, or eIF4G in Saccharomyces cerevisiae cells on binding of the
      ternary complex, other initiation factors, and RPL41A mRNA to native 43S and 48S
      preinitiation complexes. Depleting eIF2, eIF3, or eIF5 reduced 40S binding of all
      constituents of the multifactor complex (MFC), comprised of these three factors
      and eIF1, supporting a mechanism of coupled 40S binding by MFC components. 40S
      bound mRNA strongly accumulated in eIF5-depleted cells, even though MFC binding
      to 40S subunits was reduced by eIF5 depletion. Hence, stimulation of the GTPase
      activity of the ternary complex, a prerequisite for 60S subunit joining in vitro,
      is likely the rate-limiting function of eIF5 in vivo. Depleting eIF2 or eIF3
      impaired mRNA binding to free 40S subunits, but depleting eIF4G led unexpectedly
      to accumulation of mRNA on 40S subunits. Thus, it appears that eIF3 and eIF2 are
      more critically required than eIF4G for stable binding of at least some mRNAs to
      native preinitiation complexes and that eIF4G has a rate-limiting function at a
      step downstream of 48S complex assembly in vivo.

PMID- 16449649
TI  - Building of the tetraspanin web: distinct structural domains of CD81 function in
      different cellular compartments.
AB  - The tetraspanin web is composed of a network of tetraspanins and their partner
      proteins that facilitate cellular interactions and fusion events by an unknown
      mechanism. Our aim was to unravel the web partnership between the tetraspanin
      CD81 and CD19, a cell surface signaling molecule in B lymphocytes. We found that
      CD81 plays multiple roles in the processing, intracellular trafficking, and
      membrane functions of CD19. Surprisingly, these different roles are embodied in
      distinct CD81 domains, which function in the different cellular compartments: the
      N-terminal tail of CD81 has an effect on the glycosylation of CD19; the first
      transmembrane domain of CD81 is sufficient to support the exit of CD19 from the
      endoplasmic reticulum, although the large extracellular loop (LEL) of CD81
      associates physically with CD19 early during biosynthesis; and finally, the TM2
      and TM3 domains of CD81 play a role in the transmission of signals initiated upon
      engagement of the LEL. The participation of distinct CD81 domains in varied
      functions may explain the pleiotropic effects of CD81 within the tetraspanin web.

PMID- 16449650
TI  - Identification and characterization of SAP25, a novel component of the mSin3
      corepressor complex.
AB  - The transcriptional corepressor mSin3 is associated with histone deacetylases
      (HDACs) and is utilized by many DNA-binding transcriptional repressors. We have
      cloned and characterized a novel mSin3A-binding protein, SAP25. SAP25 binds to
      the PAH1 domain of mSin3A, associates with the mSin3A-HDAC complex in vivo, and
      represses transcription when tethered to DNA. SAP25 is required for mSin3A
      mediated, but not N-CoR-mediated, repression. SAP25 is a nucleocytoplasmic
      shuttling protein, actively exported from the nucleus by a CRM1-dependent
      mechanism. A fraction of SAP25 is located in promyelocytic leukemia protein (PML)
      nuclear bodies, and PML induces a striking nuclear accumulation of SAP25. An
      isotope-coded affinity tag quantitative proteomic analysis of the SAP25 complex
      revealed that SAP25 is associated with several components of the mSin3 complex,
      nuclear export machinery, and regulators of transcription and cell cycle. These
      results suggest that SAP25 is a novel core component of the mSin3 corepressor
      complex whose subcellular location is regulated by PML.

PMID- 16449651
TI  - DNA polymerase eta, the product of the xeroderma pigmentosum variant gene and a
      target of p53, modulates the DNA damage checkpoint and p53 activation.
AB  - DNA polymerase eta (PolH) is the product of the xeroderma pigmentosum variant
      (XPV) gene and a well-characterized Y-family DNA polymerase for translesion
      synthesis. Cells derived from XPV patients are unable to faithfully bypass UV
      photoproducts and DNA adducts and thus acquire genetic mutations. Here, we found
      that PolH can be up-regulated by DNA breaks induced by ionizing radiation or
      chemotherapeutic agents, and knockdown of PolH gives cells resistance to
      apoptosis induced by DNA breaks in multiple cell lines and cell types in a p53
      dependent manner. To explore the underlying mechanism, we examined p53 activation
      upon DNA breaks and found that p53 activation is impaired in PolH knockdown cells
      and PolH-null primary fibroblasts. Importantly, reconstitution of PolH into PolH
      knockdown cells restores p53 activation. Moreover, we provide evidence that, upon
      DNA breaks, PolH is partially colocalized with phosphorylated ATM at gamma-H2AX
      foci and knockdown of PolH impairs ATM to phosphorylate Chk2 and p53. However,
      upon DNA damage by UV, PolH knockdown cells exhibit two opposing temporal
      responses: at the early stage, knockdown of PolH suppresses p53 activation and
      gives cells resistance to UV-induced apoptosis in a p53-dependent manner; at the
      late stage, knockdown of PolH suppresses DNA repair, leading to sustained
      activation of p53 and increased susceptibility to apoptosis in both a p53
      dependent and a p53-independent manner. Taken together, we found that PolH has a
      novel role in the DNA damage checkpoint and that a p53 target can modulate the
      DNA damage response and subsequently regulate p53 activation.

PMID- 16449652
TI  - Distinct posttranscriptional mechanisms regulate the activity of the Zn finger
      transcription factor lame duck during Drosophila myogenesis.
AB  - Skeletal muscle formation in Drosophila melanogaster requires two types of
      myoblasts, muscle founders and fusion-competent myoblasts. Lame duck (Lmd), a
      member of the Gli superfamily of transcription factors, is essential for the
      specification and differentiation of fusion-competent myoblasts. We report herein
      that appropriate levels of active Lmd protein are attained by a combination of
      posttranscriptional mechanisms. We provide evidence that two different regions of
      the Lmd protein are critical for modulating the balance between its nuclear
      translocation and its retention within the cytoplasm. Activation of the Lmd
      protein is also tempered by posttranslational modifications of the protein that
      do not detectably change its subcellular localization. We further show that
      overexpression of Lmd protein derivatives that are constitutively nuclear or
      hyperactive results in severe muscle defects. These findings underscore the
      importance of regulated Lmd protein activity in maintaining proper activation of
      downstream target genes, such as Mef2, within fusion-competent myoblasts.

PMID- 16449653
TI  - Regulation of gross chromosomal rearrangements by ubiquitin and SUMO ligases in
      Saccharomyces cerevisiae.
AB  - Gross chromosomal rearrangements (GCRs) are frequently observed in many cancers.
      Previously, we showed that inactivation of Rad5 or Rad18, ubiquitin ligases (E3)
      targeting for proliferating cell nuclear antigen (PCNA), increases the de novo
      telomere addition type of GCR (S. Smith, J. Y. Hwang, S. Banerjee, A. Majeed, A.
      Gupta, and K. Myung, Proc. Natl. Acad. Sci. USA 101:9039-9044, 2004). GCR
      suppression by Rad5 and Rad18 appears to be exerted by the RAD5-dependent error
      free mode of bypass DNA repair. In contrast, Siz1 SUMO ligase and another
      ubiquitin ligase, Bre1, which target for PCNA and histone H2B, respectively, have
      GCR-supporting activities. Inactivation of homologous recombination (HR) proteins
      or the helicase Srs2 reduces GCR rates elevated by the rad5 or rad18 mutation.
      GCRs are therefore likely to be produced through the restrained recruitment of an
      HR pathway to stalled DNA replication forks. Since this HR pathway is compatible
      with Srs2, it is not a conventional form of recombinational pathway. Lastly, we
      demonstrate that selection of proper DNA repair pathways to stalled DNA
      replication forks is controlled by the Mec1-dependent checkpoint and is executed
      by cooperative functions of Siz1 and Srs2. We propose a mechanism for how defects
      in these proteins could lead to diverse outcomes (proper repair or GCR formation)
      through different regulation of DNA repair machinery.

PMID- 16449654
TI  - Efficient and specific targeting of Polycomb group proteins requires cooperative
      interaction between Grainyhead and Pleiohomeotic.
AB  - Specific targeting of the protein complexes formed by the Polycomb group of
      proteins is critically required to maintain the inactive state of a group of
      developmentally regulated genes. Although the role of DNA binding proteins in
      this process has been well established, it is still not understood how these
      proteins target the Polycomb complexes specifically to their response elements.
      Here we show that the grainyhead gene, which encodes a DNA binding protein,
      interacts with one such Polycomb response element of the bithorax complex.
      Grainyhead binds to this element in vitro. Moreover, grainyhead interacts
      genetically with pleiohomeotic in a transgene-based, pairing-dependent silencing
      assay. Grainyhead also interacts with Pleiohomeotic in vitro, which facilitates
      the binding of both proteins to their respective target DNAs. Such interactions
      between two DNA binding proteins could provide the basis for the cooperative
      assembly of a nucleoprotein complex formed in vitro. Based on these results and
      the available data, we propose that the role of DNA binding proteins in Polycomb
      group-dependent silencing could be described by a model very similar to that of
      an enhanceosome, wherein the unique arrangement of protein-protein interaction
      modules exposed by the cooperatively interacting DNA binding proteins provides
      targeting specificity.

PMID- 16449655
TI  - The multifunctional RNA-binding protein La is required for mouse development and
      for the establishment of embryonic stem cells.
AB  - The La protein is a target of autoantibodies in patients suffering from Sjogren's
      syndrome, systemic lupus erythematosus, and neonatal lupus. Ubiquitous in
      eukaryotes, La functions as a RNA-binding protein that promotes the maturation of
      tRNA precursors and other nascent transcripts synthesized by RNA polymerase III
      as well as other noncoding RNAs. La also associates with a class of mRNAs that
      encode ribosome subunits and precursors to snoRNAs involved in ribosome
      biogenesis. Thus, it was surprising that La is dispensable in the yeasts
      Saccharomyces cerevisiae and Schizosaccharomyces pombe, the organisms from which
      it has been characterized most extensively. To determine whether La is essential
      in mammals and if so, at which developmental stage it is required, mice were
      created with a disrupted La gene, and the offspring from La+/-intercrosses were
      analyzed. La-/- offspring were detected at the expected frequency among
      blastocysts prior to implantation, whereas no nullizygotes were detected after
      implantation, indicating that La is required early in development. Blastocysts
      derived from La+/- intercrosses yielded 38 La+/+ and La+/- embryonic stem (ES)
      cell lines but no La-/- ES cell lines, suggesting that La contributes a critical
      function toward the establishment or survival of ES cells. Consistent with this,
      La-/- blastocyst outgrowths revealed loss of the inner cell mass (ICM). The
      results indicate that in contrast to the situation in yeasts, La is essential in
      mammals and is one of a limited number of genes required as early as the
      development of the ICM.

PMID- 16449656
TI  - Induction of nitric oxide synthase-dependent telomere shortening after functional
      inhibition of Hsp90 in human tumor cells.
AB  - In most cancer cells, the lengths of telomeres, the functional DNA-protein
      complexes located at chromosome ends, are maintained by the ribonucleoprotein
      telomerase. Hsp90 facilitates the assembly of telomerase and remains associated
      with the functional complex, implying a direct involvement of Hsp90 in telomere
      length regulation. In an effort to elucidate the effects of Hsp90 inhibition on
      function and viability of human prostate cancer cells, both pharmacological
      (radicicol) and genetic (small interfering RNA) approaches were utilized to
      target Hsp90. Depletion of functional Hsp90 caused dramatic telomere shortening
      followed by apoptosis. Of particular significance, these cells exhibit a high
      level of nitric oxide synthase (NOS)-dependent free radical production, and
      simultaneous treatment of cells with the NOS inhibitor L-NAME resulted in
      telomere elongation and prevention of apoptosis. In addition, we observe
      significant DNA damage assessed by telomere dysfunction, although in the absence
      of a classical DNA damage response. Overall, our data suggest a novel mechanism
      whereby inhibition of Hsp90 disrupts free radical homeostasis and contributes
      directly to telomere erosion, further implicating Hsp90 as a potential
      therapeutic target for cancer cells.

PMID- 16449657
TI  - Pin1 regulates centrosome duplication, and its overexpression induces centrosome
      amplification, chromosome instability, and oncogenesis.
AB  - Phosphorylation on Ser/Thr-Pro motifs is a major mechanism regulating many events
      involved in cell proliferation and transformation, including centrosome
      duplication, whose defects have been implicated in oncogenesis. Certain
      phosphorylated Ser/Thr-Pro motifs can exist in two distinct conformations whose
      conversion in certain proteins is catalyzed specifically by the prolyl isomerase
      Pin1. Pin1 is prevalently overexpressed in human cancers and is important for the
      activation of multiple oncogenic pathways, and its deletion suppresses the
      ability of certain oncogenes to induce cancer in mice. However, little is known
      about the role of Pin1 in centrosome duplication and the significance of Pin1
      overexpression in cancer development in vivo. Here we show that Pin1
      overexpression correlates with centrosome amplification in human breast cancer
      tissues. Furthermore, Pin1 localizes to and copurifies with centrosomes in
      interphase but not mitotic cells. Moreover, Pin1 ablation in mouse embryonic
      fibroblasts drastically delays centrosome duplication without affecting DNA
      synthesis and Pin1 inhibition also suppresses centrosome amplification in S
      arrested CHO cells. In contrast, overexpression of Pin1 drives centrosome
      duplication and accumulation, resulting in chromosome missegregation, aneuploidy,
      and transformation in nontransformed NIH 3T3 cells. More importantly, transgenic
      overexpression of Pin1 in mouse mammary glands also potently induces centrosome
      amplification, eventually leading to mammary hyperplasia and malignant mammary
      tumors with overamplified centrosomes. These results demonstrate for the first
      time that the phosphorylation-specific isomerase Pin1 regulates centrosome
      duplication and its deregulation can induce centrosome amplification, chromosome
      instability, and oncogenesis.

PMID- 16449658
TI  - AP-1 differentially expressed proteins Krp1 and fibronectin cooperatively enhance
      Rho-ROCK-independent mesenchymal invasion by altering the function, localization,
      and activity of nondifferentially expressed proteins.
AB  - The transcription factor AP-1, which is composed of Fos and Jun family proteins,
      plays an essential role in tumor cell invasion by altering gene expression. We
      report here that Krp1, the AP-1 up-regulated protein that has a role in
      pseudopodial elongation in v-Fos-transformed rat fibroblast cells, forms a novel
      interaction with the nondifferentially expressed actin binding protein Lasp-1.
      Krp1 and Lasp-1 colocalize with actin at the tips of pseudopodia, and this
      localization is maintained by continued AP-1 mediated down-regulation of
      fibronectin that in turn suppresses integrin and Rho-ROCK signaling and allows
      pseudopodial protrusion and mesenchyme-like invasion. Mutation analysis of Lasp-1
      demonstrates that its SH3 domain is necessary for pseudopodial extension and
      invasion. The results support the concept of an AP-1-regulated multigenic
      invasion program in which proteins encoded by differentially expressed genes
      direct the function, localization, and activity of proteins that are not
      differentially expressed to enhance the invasiveness of cells.

PMID- 16449659
TI  - Evidence that Spt2/Sin1, an HMG-like factor, plays roles in transcription
      elongation, chromatin structure, and genome stability in Saccharomyces
      cerevisiae.
AB  - Spt2/Sin1 is a DNA binding protein with HMG-like domains that has been suggested
      to play a role in chromatin-mediated transcription in Saccharomyces cerevisiae.
      Previous studies have suggested models in which Spt2 plays an inhibitory role in
      the initiation of transcription of certain genes. In this work, we have taken
      several approaches to study Spt2 in greater detail. Our results have identified
      previously unknown genetic interactions between spt2Delta and mutations in genes
      encoding transcription elongation factors, including members of the PAF and
      HIR/HPC complexes. In addition, genome-wide and gene-specific chromatin
      immunoprecipitation analyses suggest that Spt2 is primarily associated with
      coding regions in a transcription-dependent fashion. Furthermore, our results
      show that Spt2, like other elongation factors, is required for the repression of
      transcription from a cryptic promoter within a coding region and that Spt2 is
      also required for repression of recombination within transcribed regions.
      Finally, we provide evidence that Spt2 plays a role in regulating the levels of
      histone H3 over transcribed regions. Taken together, our results suggest a direct
      link for Spt2 with transcription elongation, chromatin dynamics, and genome
      stability.

PMID- 16449661
TI  - The NH2 tail of the novel histone variant H2BFWT exhibits properties distinct
      from conventional H2B with respect to the assembly of mitotic chromosomes.
AB  - We have studied the functional and structural properties of nucleosomes
      reconstituted with H2BFWT, a recently identified putative histone variant of the
      H2B family with totally unknown function. We show that H2BFWT can replace the
      conventional histone H2B in the nucleosome. The presence of H2BFWT did not affect
      the overall structure of the nucleosome, and the H2BFWT nucleosomes exhibited the
      same stability as conventional nucleosomes. SWI/SNF was able to efficiently
      remodel and mobilize the H2BFWT nucleosomes. Importantly, H2BFWT, in contrast to
      conventional H2B, was unable to recruit chromosome condensation factors and to
      participate in the assembly of mitotic chromosomes. This was determined by the
      highly divergent (compared to conventional H2B) NH2 tail of H2BFWT. These data,
      in combination with the observations that H2BFWT was found by others in the sperm
      nuclei and appeared to be associated with the telomeric chromatin, suggest that
      H2BFWT could act as a specific epigenetic marker.

PMID- 16449660
TI  - Mouse disabled 1 regulates the nuclear position of neurons in a Drosophila eye
      model.
AB  - Nucleokinesis has recently been suggested as a critical regulator of neuronal
      migration. Here we show that Disabled 1 (Dab1), which is required for neuronal
      positioning in mammals, regulates the nuclear position of postmitotic neurons in
      a phosphorylation-site dependent manner. Dab1 expression in the Drosophila visual
      system partially rescues nuclear position defects caused by a mutation in the
      Dynactin subunit Glued. Furthermore, we observed that a loss-of-function allele
      of amyloid precursor protein (APP)-like, a kinesin cargo receptor, enhanced the
      severity of a Dab1 overexpression phenotype characterized by misplaced nuclei in
      the adult retina. In mammalian neurons, overexpression of APP reduced the ability
      of Reelin to induce Dab1 tyrosine phosphorylation, suggesting an antagonistic
      relationship between APP family members and Dab1 function. This is the first
      evidence that signaling which regulates Dab1 tyrosine phosphorylation determines
      nuclear positioning through Dab1-mediated influences on microtubule motor
      proteins in a subset of neurons.

PMID- 16449663
TI  - Overexpression of PKD1 causes polycystic kidney disease.
AB  - The pathogenetic mechanisms underlying autosomal dominant polycystic kidney
      disease (ADPKD) remain to be elucidated. While there is evidence that Pkd1 gene
      haploinsufficiency and loss of heterozygosity can cause cyst formation in mice,
      paradoxically high levels of Pkd1 expression have been detected in the kidneys of
      ADPKD patients. To determine whether Pkd1 gain of function can be a pathogenetic
      process, a Pkd1 bacterial artificial chromosome (Pkd1-BAC) was modified by
      homologous recombination to solely target a sustained Pkd1 expression
      preferentially to the adult kidney. Several transgenic lines were generated that
      specifically overexpressed the Pkd1 transgene in the kidneys 2- to 15-fold over
      Pkd1 endogenous levels. All transgenic mice reproducibly developed tubular and
      glomerular cysts and renal insufficiency and died of renal failure. This model
      demonstrates that overexpression of wild-type Pkd1 alone is sufficient to trigger
      cystogenesis resembling human ADPKD. Our results also uncovered a striking
      increased renal c-myc expression in mice from all transgenic lines, indicating
      that c-myc is a critical in vivo downstream effector of Pkd1 molecular pathways.
      This study not only produced an invaluable and first PKD model to evaluate
      molecular pathogenesis and therapies but also provides evidence that gain of
      function could be a pathogenetic mechanism in ADPKD.

PMID- 16449662
TI  - An E2F binding-deficient Rb1 protein partially rescues developmental defects
      associated with Rb1 nullizygosity.
AB  - Rb1 is essential for normal embryonic development, as null mice die in
      midgestation with widespread unscheduled cell proliferation. Rb1 protein (pRb)
      mediates cell cycle control by binding E2F transcription factors and repressing
      expression from E2F-dependent promoters. An increasing amount of evidence
      suggests that pRb loss also compromises cellular differentiation. Since
      differentiation is often dependent on cell cycle exit, it is currently unclear
      whether the effects of pRb on differentiation are an indirect consequence of
      pRb/E2F-mediated cell cycle control or whether they reflect direct cell-type
      specific pRb functions. We have mutated Rb1 in the mouse to express a protein
      (R654W) specifically deficient in binding E2F1, E2F2, and E2F3. R654W mutant
      embryos exhibit cell cycle defects the same as those of Rb1 null embryos,
      reinforcing the importance of the interactions of pRb with E2F1, E2F2, and E2F3
      for cell cycle control. However, R654W embryos survive at least 2 days longer
      than Rb1 null embryos, and increased life span is associated with improved
      erythrocyte and fetal liver macrophage differentiation. In contrast, R654W pRb
      does not rescue differentiation defects associated with pRb-deficient retinae.
      These data indicate that Rb1 makes important cell-type-specific contributions to
      cellular differentiation that are genetically separable from its general ability
      to stably bind E2F1, E2F2, and E2F3 and regulate the cell cycle.

PMID- 16449664
TI  - Sialoadhesin-deficient mice exhibit subtle changes in B- and T-cell populations
      and reduced immunoglobulin M levels.
AB  - Sialoadhesin (Sn, also called Siglec-1 or CD169) is a transmembrane receptor and
      the prototypic member of the Siglec family of sialic acid binding immunoglobulin
      like lectins. It is expressed on specialized subsets of resident macrophages in
      hematopoietic and lymphoid tissues and on inflammatory macrophages. In order to
      investigate its function, we generated Sn-deficient mice and confirmed that these
      mice are true nulls by fluorescence-activated cell sorter analysis and
      immunohistochemistry. Mice deficient in Sn were viable and fertile and showed no
      developmental abnormalities. Analysis of cell populations revealed no differences
      in bone marrow, peritoneal cavity, and thymus, but there was a small increase in
      CD8 T cells and a decrease in B220-positive cells in spleens and lymph nodes of
      Sn-deficient mice. Furthermore, in spleen there was a slight decrease in
      follicular B cells with an increase in numbers of marginal zone B cells. B- and T
      cell maturation as well as responses to stimulation with thioglycolate were only
      slightly affected by Sn deficiency. Immunoglobulin titers in Sn-deficient mice
      were significantly decreased for immunoglobulin M (IgM) but similar for IgG
      subclasses. These results suggest a role for sialoadhesin in regulating cells of
      the immune system rather than in influencing steady-state hematopoiesis.

PMID- 16449665
TI  - Mobilization of RAG-generated signal ends by transposition and insertion in vivo.
AB  - In addition to their essential roles in V(D)J recombination, the RAG proteins
      have been found to catalyze transposition in vitro, but it has been difficult to
      demonstrate transposition by the RAG proteins in vivo in vertebrate cells. As
      genomic instability and chromosomal translocations are common outcomes of
      transposition in other species, it is critical to understand if the RAG proteins
      behave as a transposase in vertebrate cells. To facilitate this, we have
      developed an episome-based assay to detect products of RAG-mediated transposition
      in the human embryonic kidney cell line 293T. Transposition events into the
      target episome, accompanied by characteristic target site duplications, were
      detected at a low frequency using RAG1 and either truncated "core" RAG2 or full
      length RAG2. More frequently, insertion of the RAG-generated signal end fragment
      into the target was accompanied by deletions or more complex rearrangements, and
      our data indicate that these events occur by a mechanism that is distinct from
      transposition. An assay to detect transposition from an episome into the human
      genome failed to detect bona fide transposition events but instead yielded
      chromosome deletion and translocation events involving the signal end fragment
      mobilized by the RAG proteins. These assays provide a means of assessing RAG
      mediated transposition in vivo, and our findings provide insight into the
      potential for the products of RAG-mediated DNA cleavage to cause genome
      instability.

PMID- 16449667
TI  - Inhibition of immune responses by ITAM-bearing receptors.
AB  - Cells of the immune system possess many multisubunit receptors that are composed
      of a ligand-binding subunit associated with distinct signaling adaptors
      containing one or more immunoreceptor tyrosine-based activation motifs (ITAMs).
      These receptors include the T cell receptor, the B cell receptor, and many Fc
      receptors, as well as families of activating receptors on myeloid and natural
      killer cells. Receptors that associate with ITAM-containing adaptors classically
      have been viewed as transducing activating signals involving phosphorylation of
      the tyrosines within the ITAM and recruitment of Syk family tyrosine kinases.
      Receptors associated with ITAM-containing adaptors in myeloid cells have also
      been implicated in inhibition of cellular activation. Here, we discuss these new
      negative roles for signaling by receptors that associate with ITAM-bearing
      adaptors in myeloid and other cell types within the immune system.

PMID- 16449668
TI  - Transcending the volume-outcome relationship in cancer care.

PMID- 16449669
TI  - Methylation of Stat1 promoter can contribute to squamous cell carcinogenesis.

PMID- 16449666
TI  - Essential role for protein kinase D family kinases in the regulation of class II
      histone deacetylases in B lymphocytes.
AB  - We have taken a knockout approach to interrogate the function of protein kinase D
      (PKD) serine/threonine kinases in lymphocytes. DT40 B cells express two PKD
      family members, PKD1 and PKD3, which are both rapidly activated by the B-cell
      antigen receptor (BCR). DT40 cells with single or dual deletions of PKD1 and/or
      PKD3 were viable, allowing the role of individual PKD isoforms in BCR signal
      transduction to be assessed. One proposed downstream target for PKD1 in
      lymphocytes is the class II histone deacetylases (HDACs). Regulation of chromatin
      accessibility via class II histone deacetylases is an important mechanism
      controlling gene expression patterns, but the molecules that control this key
      process in B cells are not known. Herein, we show that phosphorylation and
      nuclear export of the class II histone deacetylases HDAC5 and HDAC7 are rapidly
      induced following ligation of the BCR or after treatment with phorbol esters (a
      diacylglycerol mimetic). Loss of either PKD1 or PKD3 had no impact on HDAC
      phosphorylation, but loss of both PKD1 and PKD3 abrogated antigen receptor
      induced class II HDAC5/7 phosphorylation and nuclear export. These studies reveal
      an essential and redundant role for PKD enzymes in controlling class II HDACs in
      B lymphocytes and suggest that PKD serine kinases are a critical link between the
      BCR and epigenetic control of chromatin.

PMID- 16449670
TI  - Very early detection? British group gauges public interest in embryo testing for
      cancer.

PMID- 16449671
TI  - Agencies look to patient navigators to reduce cancer care disparities.

PMID- 16449672
TI  - Stat bite: Mortality from lung and bronchus cancer by race/ethnicity, 1998-2002.

PMID- 16449673
TI  - New data on clinical trials directive in Europe show few favorable outcomes.

PMID- 16449675
TI  - NIH Institutes launch joint venture to map cancer genome.

PMID- 16449674
TI  - Clinical trials going to the dogs: canine program to study tumor treatment,
      biology.

PMID- 16449676
TI  - Associations between hospital and surgeon procedure volumes and patient outcomes
      after ovarian cancer resection.
AB  - BACKGROUND: Strong associations between provider (i.e., hospital or surgeon)
      procedure volumes and patient outcomes have been demonstrated for many types of
      cancer operation. We performed a population-based cohort study to examine these
      associations for ovarian cancer resections. METHODS: We used the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare linked database to identify 2952
      patients aged 65 years or older who had surgery for a primary ovarian cancer
      diagnosed from 1992 through 1999. Hospital- and surgeon-specific procedure
      volumes were ascertained based on the number of claims submitted during the 8
      year study period. Primary outcome measures were mortality at 60 days and 2 years
      after surgery, and overall survival. Length of hospital stay was also examined.
      Patient age at diagnosis, race, marital status, comorbid illness, cancer stage,
      and median income and population density in the area of residence were used to
      adjust for differences in case mix. All P values are two-sided. RESULTS: Neither
      hospital- nor surgeon-specific procedure volume was statistically significantly
      associated with 60-day mortality following primary ovarian cancer resection.
      However, differences by hospital volume were seen with 2-year mortality; patients
      treated at the low-, intermediate-, and high-volume hospitals had 2-year
      mortality rates of 45.2% (95% confidence interval [CI] = 42.1% to 48.4%), 41.1%
      (95% CI = 38.1% to 44.3%), and 40.4% (95% CI = 37.4% to 43.4%), respectively. The
      inverse association between hospital procedure volume and 2-year mortality was
      statistically significant both before (P = .011) and after (P = .006) case-mix
      adjustment but not after adjustment for surgeon volume. Two-year mortality for
      patients treated by low-, intermediate-, and high-volume surgeons was 43.2% (95%
      CI = 40.7% to 45.8%), 42.9% (95% CI = 39.5% to 46.4%), and 39.5% (95% CI = 36.0%
      to 43.2%), respectively; there was no association between 2-year mortality and
      surgeon procedure volume, with or without case-mix adjustment. After case-mix
      adjustment, neither hospital volume (P = .031) nor surgeon volume (P = .062) was
      strongly associated with overall survival. CONCLUSION: Hospital- and surgeon
      specific procedure volumes are not strong predictors of survival outcomes
      following surgery for ovarian cancer among women aged 65 years or older.

PMID- 16449677
TI  - Effect of surgeon specialty on processes of care and outcomes for ovarian cancer
      patients.
AB  - BACKGROUND: For many diseases, specialized care (i.e., care rendered by a
      specialist) has been associated with superior-quality care (i.e., better
      outcomes). We examined associations between physician specialty and outcomes in a
      population-based cohort of elderly ovarian cancer surgery patients. METHODS: We
      analyzed the Medicare claims, by physician specialty, of all women aged 65 years
      or older who underwent surgery for pathologically confirmed invasive epithelial
      ovarian cancer between January 1, 1992, and December 31, 1999, while living in an
      area monitored by the Surveillance, Epidemiology, and End Results (SEER) program
      to assess important care processes (i.e., the appropriate extent of surgery and
      use of adjuvant chemotherapy) and outcomes (i.e., surgical complications, ostomy
      rates, and survival). All statistical tests were two-sided. RESULTS: Among 3067
      ovarian cancer patients who underwent surgery, 1017 patients (33%) were treated
      by a gynecologic oncologist, 1377 patients (45%) by a general gynecologist, and
      673 patients (22%) by a general surgeon. Among patients with stage I or II
      disease, those treated by a gynecologic oncologist (60%) were more likely to
      undergo lymph node dissection than those treated by a general gynecologist (36%)
      or a general surgeon (16%). Patients with stage III or IV disease were more
      likely to undergo a debulking procedure if the initial surgery was performed by a
      gynecologic oncologist (58%) than by a general gynecologist (51%) or a general
      surgeon (40%; P < .001) and were more likely to receive postoperative
      chemotherapy when operated on by a gynecologic oncologist (79%) or a general
      gynecologist (76%) than by a general surgeon (62%, P < .001). Survival among
      patients operated on by gynecologic oncologists (hazard ratio [HR] of death from
      any cause = 0.85, 95% confidence interval [CI] = 0.76 to 0.95) or general
      gynecologists (HR = 0.86, 95% CI = 0.78 to 0.96) was better than that among
      patients operated on by general surgeons. CONCLUSIONS: Ovarian cancer patients
      treated by gynecologic oncologists had marginally better outcomes than those
      treated by general gynecologists and clearly superior outcomes compared with
      patients treated by general surgeons.

PMID- 16449678
TI  - Decreased STAT1 expression by promoter methylation in squamous cell
      carcinogenesis.
AB  - BACKGROUND: Dysregulation of signal transducers and activators of transcription
      (STATs) is associated with many cancers, but no role of STAT1 in human tumor
      progression has been demonstrated. METHODS: We compared STAT1 protein expression
      in squamous cell carcinoma of the head and neck (SCCHN) tumors (n = 28) and
      normal oropharyngeal mucosa samples (n = 10) from patients without cancer as
      assessed by immunoblotting. Stable clones were established from SCCHN 1483 cells
      that were transfected with a STAT1 expression construct; cell growth and
      cisplatin-induced apoptosis of the clones and vector control-transfected 1483
      cells were compared using trypan blue exclusion and Annexin V staining and
      expression of the cyclin-dependent kinase inhibitor p21 was assayed by
      immunoblotting. The growth of STAT1-overexpressing SCCHN 1483 xenograft tumors
      was compared with that of xenograft tumors derived from cells transfected with
      vector control DNA. DNA from SCCHN tumors (n = 16) and paired peripheral blood
      lymphocytes were analyzed for STAT1 mutations and promoter methylation using
      methylation-specific polymerase chain reaction and bisulfite sequencing. SCCHN
      cell lines (PCI-15b, 1483, and UM-22B) were treated with the demethylating agent
      azacytidine alone or in combination with the cytotoxic drug cisplatin, and
      expression of STAT1 and p21 were monitored by immunoblotting. All statistical
      tests were two-sided. RESULTS: STAT1 levels were statistically significantly
      lower in the SCCHN tumors than normal mucosa (median = 0.8 relative units versus
      2.4, difference = 1.6, 95% confidence interval [CI] = 1.3 to 2.0, P < .001).
      Overexpression of STAT1 abrogated the growth of SCCHN cells and xenograft tumors
      and increased p21 expression. STAT1 expression levels of the tumors with STAT1
      promoter methylation (n = 12) were lower than those of tumors (n = 4) without
      promoter methylation of STAT1 (P = .008). Azacytidine treatment increased
      expression of STAT1 and p21 in SCCHN cell lines and increased apoptosis in
      cisplatin-treated 1483 cells compared with cisplatin treatment alone (mean =
      61.3% versus 25.8%, difference = 35.5%, 95% CI = 24.5% to 43.4%; P = .028).
      CONCLUSION: STAT1 can function as a tumor suppressor in SCCHN cells. Silencing of
      the STAT1 gene via promoter methylation may contribute to SCCHN tumor cell
      growth.

PMID- 16449680
TI  - Dynamic monitoring of oncolytic adenovirus in vivo by genetic capsid labeling.
AB  - BACKGROUND: Conditionally replicative adenoviruses represent a promising strategy
      to address the limited efficacy and safety issues associated with conventional
      cancer treatment. Despite rapid translation into human clinical trials and
      demonstrated safety, the fundamental properties of oncolytic adenovirus
      replication and spread and host-vector interactions in vivo have not been
      completely evaluated. METHODS: We developed a noninvasive dynamic monitoring
      system to detect adenovirus replication. We constructed capsid-labeled E1/E3
      deleted and wild-type adenoviruses (Ad-wt) by fusing the minor capsid protein IX
      with red fluorescent proteins mRFP1 and tdimer2(12), resulting in Ad-IX-mRFP1, Ad
      IX-tdimer2(12), and Ad-wt-IX-mRFP1. Virus DNA replication, encapsidation,
      cytopathic effect, thermostability, and binding to primary receptor (coxsackie
      adenovirus receptor) were analyzed using real-time quantitative polymerase chain
      reaction, cell viability (MTS) assay, and fluorescence microscopy. Athymic mice
      (n = 4) carrying xenograft tumors that were derived from A549 lung adenocarcinoma
      cells were intratumorally inoculated with Ad-wt-IX-mRFP1, and adenovirus
      replication was dynamically monitored with a fluorescence noninvasive imaging
      system. Correlations between fluorescence signal intensity and viral DNA
      synthesis and replication were calculated using Pearson's correlation coefficient
      (r). RESULTS: The red fluorescence label had little effect on viral DNA
      replication, encapsidation, cytopathic effect, thermostability, and coxsackie
      adenovirus receptor binding. The fluorescent signal correlated with viral DNA
      synthesis and infectious progeny production both in vitro and in vivo (in A549
      cells, r = .99 and r = .65; in tumors, r = .93 and r = .92, respectively). The
      replication efficiency of Ad-wt-IX-mRFP1 in vivo was variable, and replication
      and viral spreading and persistence were limited, consistent with clinical
      observations. CONCLUSIONS: Genetic capsid labeling provides a promising approach
      for the dynamic assessment of oncolytic adenovirus function in vivo.

PMID- 16449679
TI  - Therapeutic modulation of Akt activity and antitumor efficacy of interleukin-12
      against orthotopic murine neuroblastoma.
AB  - BACKGROUND: Patients with advanced neuroblastoma have a poor prognosis. The
      antiapoptotic protein Akt has been implicated as a possible mediator of the
      resistance of human neuroblastoma cells to apoptosis; the proapoptotic protein
      Bid, is inhibited by activated Akt. Neuroblastoma has demonstrated responsiveness
      to immunotherapeutic approaches in preclinical studies, prompting investigation
      of new therapeutic strategies based on potentiation of the host immune response,
      including the use of systemic cytokines. METHODS: We examined the antitumor
      efficacy and mechanisms of action of the central immunoregulatory cytokine
      interleukin-12 (IL-12) in mice bearing established orthotopic neuroblastoma
      tumors derived from murine TBJ and Neuro-2a cells. Cohorts of mice (10
      mice/group) bearing established orthotopic neuroblastoma tumors were injected
      intraperitoneally with IL-12 or vehicle and monitored for survival. IL-12-induced
      apoptosis within the tumor microenvironment was investigated using ribonuclease
      protection assays, nuclear staining, and electron microscopy. Protein expression
      was determined via Western blot analysis and enzyme-linked immunosorbent assays.
      Confocal microscopy was used to examine the distribution of overexpressed Bid
      enhanced green fluorescent protein fusion protein (Bid-EGFP) in TBJ cells. All
      statistical tests were two-sided. RESULTS: IL-12 induced complete tumor
      regression and long-term survival of 8 (80%) of 10 mice bearing established
      neuroblastoma tumors compared with 1 (10%) of 10 control mice (P = .0055) and
      profound tumor cell apoptosis in vivo despite the fact that TBJ and Neuro-2a
      cells were resistant to receptor-mediated apoptosis in vitro. These cells
      expressed high levels of phosphorylated Akt, a key prosurvival molecule, and Akt
      inhibitors sensitized neuroblastoma cells to apoptosis mediated by IL-12
      inducible cytokines including tumor necrosis factor-alpha and interferon-gamma in
      vitro. IL-12 increased the expression of proapoptotic genes and decreased Akt
      phosphorylation within established TBJ tumors in conjunction with activation and
      subcellular translocation of Bid. CONCLUSIONS: Our results suggest that IL-12
      overcomes a potentially critical mechanism of tumor self-defense in vivo by
      inhibiting Akt activity and imply that IL-12 may possess unique therapeutic
      activity against tumors that express high levels of activated Akt.

PMID- 16449681
TI  - Acute myeloid leukemia following Hodgkin lymphoma: a population-based study of
      35,511 patients.
AB  - Treatments for Hodgkin lymphoma are associated with large relative risks of acute
      myeloid leukemia (AML), but there are few estimates of the excess absolute risk
      (EAR), a useful measure of disease burden. One-year Hodgkin lymphoma survivors (N
      = 35,511) were identified within 14 population-based cancer registries in Nordic
      countries and North America from January 1, 1970, through December 31, 2001. We
      used Poisson regression analysis to model the EAR of AML, per 10,000 person
      years. A total of 217 Hodgkin lymphoma survivors were diagnosed with AML (10.8
      expected; unadjusted EAR = 6.2; 95% confidence interval = 5.4 to 7.1). Excess
      absolute risk for AML was highest during the first 10 years after Hodgkin
      lymphoma diagnosis but remained elevated thereafter. In subsequent analyses,
      adjusted for time since Hodgkin lymphoma diagnosis and presented for the 5-9 year
      interval, the EAR was statistically significantly (P < .001) larger in patients
      diagnosed with Hodgkin lymphoma at age 35 years and older than in those diagnosed
      before 35 years of age. The EAR of AML declined statistically significantly after
      1984 (7.0 to 4.2 and 16.4 to 9.9 in the < 35 and > or = 35 age groups,
      respectively), which may be associated with modifications in chemotherapy.

PMID- 16449682
TI  - Central nervous system toxicity induced by irinotecan.

PMID- 16449683
TI  - It is time to revise the Cochrane criteria.

PMID- 16449684
TI  - Hope and probability: patient perspectives of the meaning of numerical
      information in cancer communication.
AB  - Although the complexities inherent in human communication make it a difficult
      target for empirical investigation and systematic interpretation, it is well
      recognized that patient-provider communication can have either a powerfully
      negative or positive influence on the experience of cancer. Drawing on an
      extensive data set derived from interviews with 200 cancer patients, the authors
      examine the impact of information provided in numerical form within cancer care
      communications from the patient perspective. In this context, they present
      findings related to various uses and abuses of numbers within cancer care
      communication, and illustrate how numerical information constitutes a specialized
      communication form with considerable potency for shaping the cancer experience.
      In particular, accounts of the thematic relationship between numbers and hope,
      from the perspective of those on the receiving end of cancer care, provide a
      unique perspective from which to interpret issues of compassion, caring, and
      informed consent.

PMID- 16449685
TI  - Implementation of a statewide outcome monitoring system: lessons learned from
      substance abuse treatment provider staff.
AB  - The authors analyze the pilot implementation of a statewide automated outcome
      monitoring system (OMS) in California, using the perspectives of substance abuse
      treatment providers responsible for its day-to-day operation. To gain a better
      understanding of changes experienced by staff and their perceptions of barriers
      and facilitators of implementation, they conducted 28 focus groups designed to
      inform midstream adjustments to the system prior to its possible roll-out.
      Qualitative analysis of the focus group data revealed five important factors
      influencing implementation: the treatment provider's ethos, the time-consuming
      nature of the OMS, staff buy-in, resources, and counselor and program discretion.
      Lessons learned underscored the importance of taking into consideration aspects
      of organizational change and institutional resources and infrastructure when
      implementing a major change such as an automated OMS. Findings might be useful to
      those designing and implementing similar systems or other large organizational
      change initiatives.

PMID- 16449686
TI  - What does the use of a computerized checklist mean for patient-centered care? The
      example of a routine diabetes review.
AB  - The authors examine the interaction between nurses and patients with type 2
      diabetes during routine consultations in primary care settings in the United
      Kingdom. Through preconsultation interviews, the authors identified the patients'
      expectations. The article draws on videotaped consultations with 25 patients with
      type 2 diabetes. Using conversation analysis, the authors examine the use of a
      rigid agenda, imposed via a computerized checklist, and consider how far this is
      able to suppress the patient's agenda. They consider the potential impact for the
      patient and the factors that might encourage the clinician, and the nurse
      specifically, to adopt a narrowly task-based approach to the consultation. They
      identify two potentially conflicting strands within contemporary diabetes care,
      patient-centered practice and an emphasis on biomedical audit, and suggest that
      achievement of the former might be compromised by the demands of the latter.

PMID- 16449687
TI  - Developing and implementing a triangulation protocol for qualitative health
      research.
AB  - In this article, the authors present an empirical example of triangulation in
      qualitative health research. The Canadian Heart Health Dissemination Project
      (CHHDP) involves a national examination of capacity building and dissemination
      undertaken within a series of provincial dissemination projects. The Project's
      focus is on the context, processes, and impacts of health promotion capacity
      building and dissemination. The authors collected qualitative data within a
      parallel-case study design using key informant interviews as well as document
      analysis. Given the range of qualitative data sets used, it is essential to
      triangulate the data to address completeness, convergence, and dissonance of key
      themes. Although one finds no shortage of admonitions in the literature that it
      must be done, there is little guidance with respect to operationalizing a
      triangulation process. Consequently, the authors are feeling their way through
      the process, using this opportunity to develop, implement, and reflect on a
      triangulation protocol.

PMID- 16449688
TI  - The politics of evidence.
AB  - The evidence-based movement has influenced medical research to the point that the
      agendas and methods of qualitative inquiry are often excluded from resources of
      medical granting agencies. Yet, its narrow definition of what constitutes
      evidence and its myopic vision about health must be challenged. In this article,
      the author argues that qualitative research does contribute to a reduction in
      morbidity and mortality without the cost in dollars and lives that are
      necessarily incurred in evidence-based inquiry. She asserts that we must reframe
      our definition of evidence to meet this new ethic of inquiry--which she calls the
      ultimate ethic--as a way of conducting research.

PMID- 16449689
TI  - Proving or improving: on health care research as a form of self-reflection.
AB  - As it is, clinical trials are the gold standard of health care research, employed
      to prove that the care practices they study are good. Here, the author suggests
      that we would do better to develop research methods that work toward another
      goal: to improve care practices. This requires that we no longer foreground the
      effectiveness but, instead, investigate the various effects of interventions. If
      undesirable, they might then be tinkered with. As a part of this, the effects on
      bodily parameters and on the intricacies of daily lives should not be separated
      out but studied in connection. With examples drawn from studies into care
      practices for patients with diabetes or atherosclerosis, the author argues that
      instead of trying to turn the clinic into a laboratory, we should strive to
      support and strengthen clinical ways of working.

PMID- 16449690
TI  - Reconceptualizing qualitative evidence.
AB  - As qualitative researchers, we have not explored our own work from the
      qualitative evidence perspective. The author suggests that qualitative
      researchers need to explore the conflicting agendas of evidence-based medicine
      and qualitative inquiry, compare the anatomy of qualitative data and evidenced
      based data, and explore the autonomy of qualitative inquiry within the context of
      evidenced-based medicine. By attending to and communicating the differences in
      qualitative and quantitative evidence, and by accepting the differences in our
      research agendas, qualitative researchers will achieve the legitimacy that they
      deserve and which they require.

PMID- 16449691
TI  - What's in a number? Issues in providing evidence of impact and quality of
      research(ers).
AB  - One of the challenges facing qualitative researchers in a climate in which audit
      culture has permeated many facets of the institutions in which they research is
      how to establish the impact and quality of their research. When examining track
      records, granting institutions place significant emphasis on publication
      performance. Although the quality and impact of publications have traditionally
      been assessed by peer review, there is currently a global trend toward the
      development, refinement, and increased use of quantitative metrics, particularly
      citation analysis and journal impact factor. In this article, the authors share
      their experience of using the metrics citation analysis and journal impact factor
      in the preparation of an application for funding. Their aim is twofold: to raise
      awareness about potential issues in the practical application of these metrics;
      and to offer critique about and, they hope, "quality" to the writing and rhetoric
      concerning how to measure publication impact and quality.

PMID- 16449692
TI  - The four cornerstones of qualitative research.
AB  - Evidence-based practice (EBP) is more than the application of best research
      evidence to practice. Advocates for evidence-based medicine (EBM), the parent
      discipline of EBP, state that EBP has three, and possibly four, components: best
      research evidence, clinical expertise, and patient preferences and wants. Person
      centered physicians also advocate for the person of the practitioner as a fourth
      component. In this article, the author shows the centrality of qualitative
      research to this fuller version of EBP. She also shows how qualitative research
      has four cornerstones that parallel the four components of EBP.

PMID- 16449693
TI  - The publication of qualitative research findings.
AB  - The publication of research findings is sometimes considered almost unrelated to
      the research, as something "coming after," when the research is complete. The
      essence of this short article is an argument against this idea. However, a common
      problem is that the form of publication is ruled not by the research but by, for
      example, research tradition. In Sweden, it has been common to publish extensive
      findings in the social sciences as reports, whereas in medicine and in nursing
      science linked with medicine faculties, publication in the form of international
      articles is the dominant style. The author discusses the "pro" and "cons" of
      these two publication styles. As a conclusion, she argues that we need to make
      explicit the internal paradigmatic demands on qualitative research regarding
      validity, generalization, number of informants, and, not least, publication,
      instead of allowing the old, positivistic paradigm to continue to determine the
      styles of publication.

PMID- 16449694
TI  - Two-week delay in onset of action of antidepressants: new evidence.
AB  - Many sources purport that antidepressants have a delayed onset of action,
      measured in weeks rather than days. Recent data using weekly or daily mood
      ratings demonstrate that maximum improvement occurs during the first 2 weeks,
      with some improvement within the first 3 days. Methodological issues may underlie
      the delayed-onset hypothesis.

PMID- 16449695
TI  - The future of cognitive-behavioural therapy for psychosis: not a quasi
      neuroleptic.
AB  - Some 20 trials of cognitive - behavioural therapy (CBT) for psychosis have re
      established psychotherapy as a credible treatment for psychosis. However, it is
      not without its detractors and problems, including uncertainty about the nature
      of its active ingredients. We believe that the way forward is to abandon the
      neuroleptic metaphor of CBT for psychosis and to develop targeted interventions
      that are informed by the growing understanding of the interface between emotion
      and psychosis.

PMID- 16449696
TI  - Complementary medicines in psychiatry: review of effectiveness and safety.
AB  - BACKGROUND: The use of complementary medicines in those with mental health
      problems is well documented. However, their effectiveness is often not
      established and they may be less harmless than commonly assumed. AIMS: To review
      the complementary medicines routinely encountered in psychiatric practice, their
      effectiveness, potential adverse effects and interactions. METHOD: Electronic and
      manual literature search on the effectiveness and safety of psychotropic
      complementary medicines. RESULTS: Potentially useful substances include ginkgo
      and hydergine as cognitive enhancers, passion flower and valerian as sedatives,
      St John's wort and s-adenosylmethionine as antidepressants, and selenium and
      folate to complement antidepressants. The evidence is less conclusive for the use
      of omega-3 fatty acids as augmentation treatment in schizophrenia, melatonin for
      tardive dyskinesia and 18-methoxycoronaridine, an ibogaine derivative, for the
      treatment of cocaine and heroin addiction. CONCLUSIONS: Systematic clinical
      trials are needed to test promising substances. Meanwhile, those wishing to take
      psychotropic complementary medicines require appropriate advice.

PMID- 16449698
TI  - Neuroleptics and mortality: a 50-year cycle: Invited commentary on...
      Schizophrenia, neuroleptic medication and mortality.

PMID- 16449697
TI  - Schizophrenia, neuroleptic medication and mortality.
AB  - BACKGROUND: There is an excess of death from natural causes among people with
      schizophrenia. AIMS: Schizophrenia and its treatment with neuroleptics were
      studied for their prediction of mortality in a representative population sample
      of 7217 Finns aged >/= 30 years. METHOD: A comprehensive health examination was
      carried out at baseline. Schizophrenia was determined using the Present State
      Examination and previous medical records. RESULTS: During a 17-year follow-up, 39
      of the 99 people with schizophrenia died. Adjusted for age and gender, the
      relative mortality risk between those with schizophrenia and others was 2.84 (95%
      CI 2.06-3.90), and was 2.25 (95% CI1.61-3.15) after further adjusting for somatic
      diseases, bloodpressure, cholesterol, body mass index, smoking, exercise, alcohol
      intake and education. The number of neuroleptics used at the time of the baseline
      survey showed a graded relation to mortality. Adjusted for age, gender, somatic
      diseases and other potential risk factors for premature death, the relative risk
      was 2.50 (95% CI1.46-4.30) per increment of one neuroleptic. CONCLUSIONS: There
      is an urgent need to ascertain whether the high mortality in schizophrenia is
      attributable to the disorder itself or the antipsychotic medication.

PMID- 16449699
TI  - Suicide in mental health in-patients and within 3 months of discharge. National
      clinical survey.
AB  - BACKGROUND: Suicide prevention is a health service priority. Suicide risk may be
      greatest during psychiatric in-patient admission and following discharge. AIMS:
      To describe the social and clinical characteristics of a comprehensive sample of
      in-patient and post-discharge cases of suicide. METHOD: A national clinical
      survey based on a 4-year (1996-2000) sample of cases of suicide in England and
      Wales who had been in recent contact with mental health services (n=4859).
      RESULTS: There were 754 (16%) current in-patients and a further 1100 (23%) had
      been discharged from psychiatric in-patient care less than 3 months before death.
      Nearly a quarter of the in-patient deaths occurred within the first 7 days of
      admission; 236 (31%) occurred on the ward, the majority by hanging. Post
      discharge suicide was most frequent in the first 2 weeks after leaving hospital;
      the highest number occurred on the first day. CONCLUSIONS: Suicide might be
      prevented among in-patients by improving ward design and removing fixtures that
      can be used in hanging. Prevention of suicide after discharge requires early
      community follow-up and closer supervision of high-risk patients.

PMID- 16449700
TI  - Suicide within 12 months of mental health service contact in different age and
      diagnostic groups: National clinical survey.
AB  - BACKGROUND: Suicide prevention is a health service priority but the most
      effective approaches to prevention may differ between different patient groups.
      AIMS: To describe social and clinical characteristics in cases of suicide from
      different age and diagnostic groups. METHOD: A national clinical survey of a 4
      year (1996-2000) sample of cases of suicide in England and Wales where there had
      been recent (<1 year) contact with mental health services (n=4859). RESULTS:
      Deaths of young patients were characterised by jumping from a height or in front
      of a vehicle, schizophrenia, personality disorder, unemployment and substance
      misuse. In older patients, drowning, depression, living alone, physical illness,
      recent bereavement and suicide pacts were more common. People with schizophrenia
      were often in-patients and died by violent means. About a third of people with
      depressive disorder died within a year of illness onset. Those with substance
      dependence or personality disorder had high rates of disengagement from services.
      CONCLUSIONS: Prevention measures likely to benefit young people include targeting
      schizophrenia, dual diagnosis and loss of service contact; those aimed at
      depression, isolation and physical ill-health should have more effect on elderly
      people.

PMID- 16449701
TI  - Rates of mental disorder in people convicted of homicide. National clinical
      survey.
AB  - BACKGROUND: Previous studies of people convicted of homicide have used different
      definitions of mental disorder. AIMS: To estimate the rate of mental disorder in
      people convicted of homicide; to examine the relationship between definitions,
      verdict and outcome in court. METHOD: A national clinical survey of people
      convicted of homicide (n=1594) in England and Wales (1996-1999). Rates of mental
      disorder were estimated based on: lifetime diagnosis, mental illness at the time
      of the offence, contact with psychiatric services, diminished responsibility
      verdict and hospital disposal. RESULTS: Of the 1594,545 (34%) had a mental
      disorder: most had not attended psychiatric services; 85 (5%) had schizophrenia
      (lifetime); 164 (10%) had symptoms of mental illness at the time of the offence;
      149 (9%) received a diminished responsibility verdict and 111 (7%) a hospital
      disposal - both were associated with severe mental illness and symptoms of
      psychosis. CONCLUSIONS: The findings suggest an association between schizophrenia
      and conviction for homicide. Most perpetrators with a history of mental disorder
      were not acutely ill or under mental healthcare at the time of the offence. Some
      perpetrators receive prison sentences despite having severe mental illness.

PMID- 16449702
TI  - Cannabis use and mental health in secondary school children. Findings from a
      Dutch survey.
AB  - BACKGROUND: Cannabis use is associated with mental health problems, and young
      people in particular are at risk. AIMS: To investigate the association between
      cannabis use and mental health in adolescence. METHOD: Data from 5551 adolescents
      aged 12-16 years were drawn from the Dutch Health Behaviour in School-Aged
      Children school survey, carried out aspart of the international 2001 World Health
      Organization project. RESULTS: After adjusting for confounding factors, cannabis
      use was linked to externalising problems (delinquent and aggressive behaviour)
      but not to internalising problems (withdrawn behaviour, somatic complaints and
      depression). An increasing frequency of use resulted in stronger links. No
      significant gender or age by cannabis interaction effects were found.
      CONCLUSIONS: In a country with a liberal drug policy like The Netherlands,
      cannabis use is associated with aggression and delinquency, just as in other
      countries. Cannabis use was not associated with internalising problems. Alcohol
      use and regular smoking were strong confounding factors.

PMID- 16449703
TI  - Trauma exposure in pre-school children in a war zone.
AB  - BACKGROUND: There has been little reported research into the effect of war on the
      behaviour and emotional well-being of pre-school children. AIMS: To investigate
      the relationship between exposure to war trauma and behavioural and emotional
      problems among pre-school children. METHOD: A total of 309 children aged 3-6
      years were selected from kindergartens in the Gaza Strip, and were assessed by
      parental reports in regard to their exposure to war trauma, using the Gaza
      Traumatic Checklist, and their behavioural and emotional problems, using the
      Behaviour Checklist (BCL) and the Strengths and Difficulties Questionnaire (SDQ).
      RESULTS: Pre-school children were exposed to a wide range of traumatic events.
      The total number of traumatic events independently predicted total BCL and SDQ
      scores. Exposure to day raids and shelling of the children's houses by tanks were
      significantly associated with total behavioural and emotional problems scores.
      CONCLUSIONS: Direct and non-direct exposure to war trauma increases the risk of
      behavioural and emotional problems among pre-school children, which may present
      as non-specific psychopathology.

PMID- 16449704
TI  - Psychiatric morbidity among sentenced prisoners: prevalence study in Iran.
AB  - BACKGROUND: Information on psychiatric morbidity of prisoners has almost entirely
      been based on research in Western countries and it is uncertain whether these
      research findings are applicable to other settings. AIMS: The primary objective
      was to investigate the prevalence of psychiatric disorders in Iranian prisoners.
      METHOD: Through stratified random sampling, 351 prisoners were interviewed using
      the clinical version of the Structured Clinical Interview for DSM-IV Axis I
      Disorders and the Psychopathy Checklist: Screening Version. RESULTS: The majority
      (88%) of prisoners met DSM-IV criteria for lifetime diagnosis of at least one
      Axis I disorder and 57% were diagnosed with current Axis I disorders. Opioid
      dependence (73%) had the highest prevalence among lifetime diagnoses, whereas
      major depressive disorder (29%) was the most common current diagnosis.
      Psychopathy was recorded in 23%. Prevalence rates of psychiatric disorders were
      significantly different among offence categories. CONCLUSIONS: The results
      suggest that a substantial burden of psychiatric morbidity exists in the prison
      population of Iran, with treatment challenges that appear to be different from
      those observed in inmates in Western countries.

PMID- 16449705
TI  - Psychological impact of stillbirth on fathers in the subsequent pregnancy and
      puerperium.
AB  - BACKGROUND: Approximately 1 in 200 UK pregnancies ends in stillbirth. Although
      serious psychological effects of stillbirth on mothers are well established, much
      less is known about the impact of such loss on fathers. AIMS: To assess the
      psychological morbidity of fathers in the pregnancy and post-partum year
      subsequent to a stillbirth, to test within-couple effects and to identify risk
      factors. METHOD: This was a community-based cohort study of 38 pregnant couples
      whose previous pregnancy had ended in stillbirth, and 38 pair-matched controls.
      Psychological assessments took place antenatally and at 6 weeks, 6 months and 1
      year postnatally. RESULTS: Fathers in the index group experienced significant
      levels of anxiety and post-traumatic stress disorder antenatally, but all of
      their symptoms remitted postnatally (after the birth of a live baby). Fathers'
      symptom levels were lower than those of mothers at all time points. In contrast
      to mothers, fathers experienced greater anxiety when a subsequent pregnancy
      (following stillbirth) was delayed. CONCLUSIONS: The vulnerability of fathers to
      psychological distress during the pregnancy after a stillbirth needs to be
      recognised.

PMID- 16449706
TI  - Influence of carer expressed emotion and affect on relapse in non-affective
      psychosis.
AB  - BACKGROUND: High expressed emotion in carers predicts relapse in psychosis, but
      it is not known why this is so. In our cognitive model of psychosis, we
      postulated that the effect is mediated through affective changes. AIMS: To
      investigate the relationships between carer expressed emotion, patients' symptoms
      and carer characteristics during a recent relapse of psychosis. METHOD: A total
      of 86 patients and carers were investigated in a cross-sectional design. RESULTS:
      Patients whose carers showed high expressed emotion had significantly higher
      levels of anxiety and depression, but not more psychotic symptoms or lower self
      esteem. Linear regression showed that carers'critical comments predicted anxiety
      in patients. Critical comments were related to low carer self-esteem and avoidant
      coping strategies. Low carer self-esteem was also related to carer depression,
      stress and carer 'burden', and to low patient self-esteem. CONCLUSIONS: Our
      hypothesis was partially supported. Carer criticism was associated with patient
      anxiety, low carer self-esteem and poor carer coping strategies. Family
      interventions should focus on improving these after a relapse of symptoms of
      psychosis.

PMID- 16449707
TI  - Brain white-matter hyperintensities and treatment outcome in major depressive
      disorder.
AB  - BACKGROUND: An increased incidence of brain white-matter hyperintensities has
      been described in major depressive disorder, butthe impact of such
      hyperintensities on treatment outcome is still controversial. AIMS: To
      investigate the relationship of brain white-matter hyperintensities with
      cardiovascular risk factors and with treatment outcome in younger people with
      major depressive disorder. METHOD: We assessed brain white-matter
      hyperintensities and cardiovascular risk factors in 84 people with major
      depressive disorder prior to initiating antidepressant treatment. We also
      assessed hyperintensities in 35 matched controls. RESULTS: We found no
      significant difference in the prevalence of white-matter hyperintensities between
      the depression and the control groups. Left-hemisphere subcortical
      hyperintensities correlated with lower rates of treatment response. We found no
      correlation between global hyperintensity measures and clinical outcome. Brain
      white-matter hyperintensities correlated with hypertension and age and withtotal
      cardiovascular risk score. CONCLUSIONS: Subcortical white-matter hyperintensities
      in the left hemisphere (but notin other brain areas) maybe associated with poor
      response to antidepressant treatment in major depression.

PMID- 16449708
TI  - Intellectual asymmetry and genetic liability in first-degree relatives of
      probands with schizophrenia.
AB  - Intellectual asymmetry with superiority of verbal skills to spatial skills
      frequently characterises patients with schizophrenia, but it is unclear whether
      this pattern also reflects genetic susceptibility to the disorder. We examined
      the association of a continuous measure of genetic liability to schizophrenia
      with Verbal-Spatial Contrast IQ (an index of intellectual asymmetry) in 108 first
      degree relatives without psychosis of probands with schizophrenia. Higher genetic
      liability was significantly associated with greater intellectual asymmetry in
      favour of verbal skills. Intellectual asymmetry with a relative superiority of
      verbal skills to spatial skills represents a putative endophenotype of
      schizophrenia.

PMID- 16449709
TI  - Long-term outcome of two forms of randomised benzodiazepine discontinuation.
AB  - About two-thirds of long-term users of benzodiazepines in the population are able
      to discontinue this drug with the aid of supervised programmes for tapering off.
      Little is known about the long-term outcome of such programmes, and they have
      never been compared with usual care. After a 15-month follow-up of a randomised
      controlled trial comparing such a programme with and without psychotherapy with
      usual care, we found significantly higher longitudinal abstinence rates in long
      term benzodiazepine users who received a benzodiazepine tapering-off programme
      without psychotherapy (25 out of 69, 36%) compared with those who received usual
      care (5 out of 33,15%; P=0.03).

PMID- 16449711
TI  - Devaluation of PTSD.

PMID- 16449710
TI  - Time for a broad phenotype in schizophrenia?

PMID- 16449712
TI  - Schizophrenia, weight gain and atypical antipsychotics.

PMID- 16449713
TI  - Cancer and schizophrenia.

PMID- 16449714
TI  - Brief psychotherapy for Alzheimer's disease.

PMID- 16449715
TI  - Akathisia as a risk factor for suicide.

PMID- 16449716
TI  - Call for a European guidelines institute.

PMID- 16449717
TI  - Cardiology patient page. On-pump and off-pump coronary artery bypass grafting.

PMID- 16449718
TI  - Images in cardiovascular medicine. Giant right atrium in the setting of desmin
      related restrictive cardiomyopathy.

PMID- 16449719
TI  - Images in cardiovascular medicine. Fetal cardiac diverticulum.

PMID- 16449720
TI  - Images in cardiovascular medicine. Multislice computed tomography evaluation 21
      years after heterotopic heart transplantation.

PMID- 16449721
TI  - Letter regarding article by Tonelli et al, "effect of pravastatin on rate of
      kidney function loss in people with or at risk for coronary disease".

PMID- 16449722
TI  - A view from Sweden, January 31, 2006.

PMID- 16449723
TI  - Electrocardiography in women: taking the initiative.

PMID- 16449724
TI  - Angina and cardiac care: are there gender differences, and if so, why?

PMID- 16449725
TI  - "Bridging" and mechanical heart valves: perils, promises, and predictions.

PMID- 16449726
TI  - Electrocardiographic abnormalities that predict coronary heart disease events and
      mortality in postmenopausal women: the Women's Health Initiative.
AB  - BACKGROUND: Information is limited about the independent prognostic value of
      repolarization abnormalities in women. METHODS AND RESULTS: We evaluated hazard
      ratios for ECG variables for combined fatal and nonfatal coronary heart disease
      (CHD) events and for CHD mortality using Cox regression in 38,283 Women's Health
      Initiative (WHI) participants during up to 9.2 years of follow-up. All risk
      models were adjusted for demographic, clinical, and therapeutic variables.
      Evaluated as single ECG variables, wide QRS/T angle and ECG-demonstrated
      myocardial infarction (ECG-MI) were the strongest predictors of CHD events, with
      hazard ratios (95% CI) of 1.90 (1.50 to 2.42) and 1.62 (1.29 to 2.03),
      respectively. Six other repolarization variables were also significant, strong
      predictors of CHD events. Wide QRS/T angle, ECG-MI, and QT prolongation appeared
      as dominant predictors when evaluated simultaneously with other ECG variables in
      a multiadjusted risk model. QRS/T angle, ECG-MI, and high QRS nondipolar voltage
      were the strongest predictors of CHD mortality, with hazard ratios of 2.70, 2.41,
      and 2.18, respectively. The risk increase ranged from 63% to 95% for the other 4
      significant predictors. Five ECG abnormalities were identified as dominant
      mortality risk predictors: wide QRS/T angle, ECG-MI, high QRS nondipolar voltage,
      reduced heart rate variability, and QT prolongation (in the cardiovascular
      disease-free group only). CONCLUSIONS: Ventricular repolarization abnormalities
      in postmenopausal women are as important predictors of CHD events and CHD
      mortality as ECG-MI and other QRS abnormalities. Repolarization variables and QRS
      nondipolar voltage warrant attention in future investigations.

PMID- 16449727
TI  - Electrocardiographic predictors of incident congestive heart failure and all
      cause mortality in postmenopausal women: the Women's Health Initiative.
AB  - BACKGROUND: Information is limited about ECG predictors of the risk of incident
      congestive heart failure (CHF), particularly in women without overt
      manifestations of cardiovascular disease (CVD). METHODS AND RESULTS: We evaluated
      hazard ratios for incident CHF and all-cause mortality using Cox regression in
      38,283 participants of the Women's Health Initiative (WHI) during a 9-year follow
      up. All risk models were adjusted for demographic and available clinical and
      therapeutic variables (multivariable-adjusted models). A backward selection
      procedure was used to identify dominant predictors among those that were
      significant as individual ECG predictors. Eleven ECG variables were significant
      predictors of incident CHF, with none of them having a significant interaction
      with baseline CVD status. From 6 dominant ECG predictors, wide QRS/T angle had a
      nearly 3-fold increased risk in multivariable-adjusted single ECG variable
      models. Two other repolarization variables, STV5 depression and high TV1
      amplitude, and 2 QRS-related variables, QRS non-dipolar voltage and myocardial
      infarction (MI) by ECG, were all associated with &2-fold increase of incident CHF
      risk. Overall, 11 of the 12 ECG variables were significant predictors of all
      cause mortality. Four variables had a significant interaction with CVD status
      requiring stratification. Three among these 4 were strong, dominant predictors in
      the CVD group: ECG MI, wide QRS/T angle, and low TV5 amplitude had risk increase
      from >2-fold to 3-fold, with considerably lower risks in the CVD-free group.
      CONCLUSIONS: Several repolarization variables in postmenopausal women are
      predictors of the risk of incident CHF and all-cause mortality as important as
      old ECG MI.

PMID- 16449728
TI  - Gender differences in the management and clinical outcome of stable angina.
AB  - BACKGROUND: We sought to examine the impact of gender on the investigation and
      subsequent management of stable angina and to assess gender differences in
      clinical outcome at 1 year. METHODS AND RESULTS: The Euro Heart Survey of Stable
      Angina enrolled patients with a clinical diagnosis of stable angina on initial
      assessment by a cardiologist. Baseline clinical details and cardiac
      investigations planned or performed within a 4-week period of the assessment were
      recorded, and follow-up data were collected at 1 year. A total of 3779 patients
      were included in the survey; 42% were female. Women were less likely to undergo
      an exercise ECG (odds ratio, 0.81; 95% CI, 0.69 to 0.95) and less likely to be
      referred for coronary angiography (odds ratio, 0.59; 95% CI, 0.48 to 0.72).
      Antiplatelet and statin therapies were used significantly less in women than in
      men, both at initial assessment and at 1 year, even in those in whom coronary
      disease had been confirmed. Women with confirmed coronary disease were less
      likely to be revascularized than their male counterparts and were twice as likely
      to suffer death or nonfatal myocardial infarction during the 1-year follow-up
      period (hazard ratio, 2.09; 95% CI, 1.13 to 3.85), even after multivariable
      adjustment for age, abnormal ventricular function, severity of coronary disease,
      and diabetes. CONCLUSIONS: Significant gender bias has been identified in the use
      of investigations and evidence-based medical therapy in stable angina. Women were
      also less likely to be revascularized. The observed bias is of particular concern
      in light of the adverse prognosis observed among women with stable angina and
      confirmed coronary disease.

PMID- 16449729
TI  - Obesity as compared with physical activity in predicting risk of coronary heart
      disease in women.
AB  - BACKGROUND: The comparative importance of physical inactivity and obesity as
      predictors of coronary heart disease (CHD) risk remains unsettled. METHODS AND
      RESULTS: We followed 88 393 women, 34 to 59 years of age, in the Nurses' Health
      Study from 1980 to 2000. These participants did not have cardiovascular disease
      and cancer at baseline. We documented 2358 incident major CHD events (including
      nonfatal myocardial infarction and fatal CHD) during 20 years of follow-up,
      including 889 cases of fatal CHD and 1469 cases of nonfatal myocardial
      infarction. In a multivariate model adjusting for cardiovascular risk factors,
      overweight and obesity were significantly associated with increased risk of CHD,
      whereas increasing levels of physical activity were associated with a graded
      reduction in CHD risk (P<0.001). In joint analyses of body mass index (BMI) and
      physical activity in women who had a healthy weight (BMI, 18.5 to 24.9 kg/m2) and
      were physically active (exercise > or =3.5 h/wk) as the reference group, the
      relative risks of CHD were 3.44 (95% confidence interval [CI], 2.81 to 4.21) for
      women who were obese (BMI > or =30 kg/m2) and sedentary (exercise <1 h/wk), 2.48
      (95% CI, 1.84 to 3.34) for women who were active but obese, and 1.48 (95% CI,
      1.24 to 1.77) for women who had a healthy weight but were sedentary. In combined
      analyses of waist-hip ratio and physical activity, both waist-hip ratio and
      physical activity were significant predictors of CHD, and the highest risk was
      among women in the lowest category of physical activity and the highest tertile
      of waist-hip ratio (relative risk=3.03; 95% CI, 1.96 to 4.18). Even a modest
      weight gain (4 to 10 kg) during adulthood was associated with 27% (95% CI, 12% to
      45%) increased risk of CHD compared with women with a stable weight after
      adjusting for physical activity and other cardiovascular risk factors.
      CONCLUSIONS: Obesity and physical inactivity independently contribute to the
      development of CHD in women. These data underscore the importance of both
      maintaining a healthy weight and regular physical activity in preventing CHD.

PMID- 16449730
TI  - Gender differences in outcomes after hospital discharge from coronary artery
      bypass grafting.
AB  - BACKGROUND: There are few comparative data regarding long-term nonfatal outcomes
      for women versus men after coronary artery bypass grafting (CABG). This study
      compares gender differences in cardiac events in a population of hospital
      survivors up to 11 years after isolated CABG surgery in Ontario, Canada. METHODS
      AND RESULTS: A population-based cohort study (n=68,774 patients, 15,043 women)
      between September 1, 1991, and April 1, 2002, was assembled with linked clinical
      and administrative databases. Cox modeling and propensity score matching were
      used to compare death, cardiac readmission (angina, heart failure, myocardial
      infarction), repeat revascularization (angioplasty or CABG), and stroke
      readmission between men and women. Women were older (65+/-17 versus 62+/-13
      years), more likely to present with urgent or emergent status (64% versus 56%),
      and less likely to receive arterial grafts (70% versus 78%). Women had a higher
      rate of cardiac readmission in the first year after surgery (hazard ratio [HR] of
      1.5, 95% confidence interval [CI] 1.36 to 1.56), and this increased risk
      persisted after 1 year (HR 1.2, 95% CI 1.14 to 1.31). This was primarily due to
      readmissions for unstable angina (HR 1.3, 95% CI 1.24 to 1.38) and congestive
      heart failure (HR 1.1, 95% CI 1.06 to 1.21). Propensity-matched women had similar
      rates of death (HR 0.9, 95% CI 0.83 to 0.98) and repeat revascularization (HR
      1.0, 95% CI 0.91 to 1.06). CONCLUSIONS: Women have a more complex clinical
      preoperative presentation and are more likely to be readmitted with unstable
      angina and congestive heart failure after CABG but experience survival similar to
      those seen in men. Gender differences in outcomes may be improved through durable
      revascularization strategies and close postoperative follow-up care targeted to
      women.

PMID- 16449731
TI  - Pregnancy outcomes in women with congenital heart disease.
AB  - BACKGROUND: Pregnant women with congenital heart disease are at increased risk
      for cardiac and neonatal complications, yet risk factors for adverse outcomes are
      not fully defined. METHODS AND RESULTS: Between January 1998 and September 2004,
      90 pregnancies at age 27.7+/-6.1 years were followed in 53 women with congenital
      heart disease. Spontaneous abortions occurred in 11 pregnancies at 10.8+/-3.7
      weeks, and 7 underwent elective pregnancy termination. There were no maternal
      deaths. Primary maternal cardiac events complicated 19.4% of ongoing pregnancies,
      with pulmonary edema in 16.7% and sustained arrhythmias in 2.8%. Univariate risk
      factors included prior history of heart failure (odds ratio [OR], 15.5), NYHA
      functional class > or =2 (OR, 5.4), and decreased subpulmonary ventricular
      ejection fraction (OR, 7.7). Independent predictors were decreased subpulmonary
      ventricular ejection fraction and/or severe pulmonary regurgitation (OR, 9.0) and
      smoking history (OR, 27.2). Adverse neonatal outcomes occurred in 27.8% of
      ongoing pregnancies and included preterm delivery (20.8%), small for gestational
      age (8.3%), respiratory distress syndrome (8.3%), intraventricular hemorrhage
      (1.4%), intrauterine fetal demise (2.8%), and neonatal death (1.4%). A subaortic
      ventricular outflow tract gradient >30 mm Hg independently predicted an adverse
      neonatal outcome (OR, 7.5). Cardiac risk assessment was improved by including
      decreased subpulmonary ventricular systolic function and/or severe pulmonary
      regurgitation (OR, 10.3) in a previously proposed risk index developed in
      pregnant women with acquired and congenital heart disease. CONCLUSIONS: Maternal
      cardiac and neonatal complication rates are considerable in pregnant women with
      congenital heart disease. Patients with impaired subpulmonary ventricular
      systolic function and/or severe pulmonary regurgitation are at increased risk for
      adverse cardiac outcomes.

PMID- 16449732
TI  - National study of women's awareness, preventive action, and barriers to
      cardiovascular health.
AB  - BACKGROUND: There is growing awareness of cardiovascular disease (CVD) as the
      leading cause of death in women, but whether this greater awareness is associated
      with increased action by women to lower their personal or family's risk is
      unknown. METHODS AND RESULTS: A nationally representative sample of 1008 women
      selected through random-digit dialing were given a standardized questionnaire
      about history of CVD/risk factors, awareness of leading cause of death, knowledge
      of healthy and personal levels of CVD risk factors, self-reported actions taken
      to reduce risk, and barriers to heart health. The rate of awareness of CVD as the
      leading cause of death has nearly doubled since 1997 (55% versus 30%) was
      significantly greater for whites compared with blacks and Hispanics (62% versus
      38% and 34%, respectively) and was independently correlated with increased
      physical activity (odds ratio, 1.35; 95% CI, 1.00 to 1.83) and weight loss (odds
      ratio, 1.47; 95% CI, 1.14 to 2.02) in the previous year in logistic regression
      models. Fewer than half of the respondents were aware of healthy levels of risk
      factors. Awareness that personal level was not healthy was positively associated
      with action. Most women took steps to lower risk in family members and
      themselves. The most frequently cited barriers for heart health were confusion in
      the media (49%), the belief that health is determined by a higher power (44%),
      and caretaking responsibilities (36%). CONCLUSIONS: General awareness of CVD risk
      among women is associated with preventive action. Educational interventions need
      to be targeted at racial/ethnic minority women.

PMID- 16449733
TI  - Preventive effect of erythropoietin on cardiac dysfunction in doxorubicin-induced
      cardiomyopathy.
AB  - BACKGROUND: Doxorubicin is a highly effective antineoplastic drug, but its
      clinical use is limited by its adverse side effects on the heart. We investigated
      possible protective effects of erythropoietin against doxorubicin-induced
      cardiomyopathy. METHODS AND RESULTS: Cardiomyopathy was induced in mice by a
      single intraperitoneal injection of doxorubicin (15 mg/kg). In some cases, human
      recombinant erythropoietin (5000 U/kg) was started simultaneously. Two weeks
      later, left ventricular dilatation and dysfunction were apparent in mice given
      doxorubicin but were significantly attenuated by erythropoietin treatment.
      Erythropoietin also protected hearts against doxorubicin-induced cardiomyocyte
      atrophy and degeneration, myocardial fibrosis, inflammatory cell infiltration,
      and downregulation of expression of GATA-4 and 3 sarcomeric proteins, myosin
      heavy chain, troponin I, and desmin. Cyclooxygenase-2 expression was upregulated
      in doxorubicin-treated hearts, and that, too, was attenuated by erythropoietin.
      No doxorubicin-induced apoptotic effects were seen, nor were any changes seen in
      the expression of tumor necrosis factor-alpha or transforming growth factor
      beta1. Antiatrophic and GATA-4 restoring effects of erythropoietin were
      demonstrated in the in vitro experiments with cultured cardiomyocytes exposed to
      doxorubicin, which indicated the direct cardioprotective effects of
      erythropoietin beyond erythropoiesis. Cardiac erythropoietin receptor expression
      was downregulated in doxorubicin-induced cardiomyopathy but was restored by
      erythropoietin. Among the downstream mediators of erythropoietin receptor
      signaling, activation of extracellular signal-regulated kinase was reduced by
      doxorubicin but restored by erythropoietin. By contrast, erythropoietin was
      ineffective when administered after cardiac dysfunction was established in the
      chronic stage. CONCLUSIONS: The present study indicates a protective effect of
      erythropoietin against doxorubicin-induced cardiomyopathy.

PMID- 16449734
TI  - Low-molecular-weight heparin as a bridging anticoagulant early after mechanical
      heart valve replacement.
AB  - BACKGROUND: After mechanical heart valve replacement (MHVR), long-term use of
      unfractionated heparin is sometimes required because vitamin K antagonists (VKA)
      are temporarily contraindicated or because the time to reach the target
      international normalized ratio is long. The aim of this study was to investigate
      the feasibility of low-molecular-weight heparin treatment in these patients.
      METHODS AND RESULTS: This work was conducted as a prospective study. We selected
      all patients (n=695) who underwent MHVR and were transferred to a postoperative
      cardiac rehabilitation center between January 2000 and January 2005. The study
      focused on patients who had not yet started VKA therapy or who had a below-target
      international normalized ratio despite VKA therapy. Unfractionated heparin was
      replaced by enoxaparin (100 IU/kg BID) until VKA treatment was fully effective.
      Two hundred fifty patients (60+/-11 years old) were enrolled 16+/-11 days after
      surgery (aortic valve replacement, n=190; mitral valve replacement, n=34; double
      valve replacement, n=26). Of these, 50% had permanent or transient atrial
      fibrillation, 40% had hypertension, 13% had diabetes, and 19% had a history of
      cardiac surgery. The mean duration of low-molecular-weight heparin treatment was
      8.3+/-6.0 days. Patients were followed for 90 days, during which there were two
      major and three minor bleeding episodes and one transient ischemic attack. There
      were no cases of valve thrombosis and no deaths. CONCLUSIONS: After MHVR, one
      third of patients leave the cardiac surgery unit before VKA treatment is fully
      effective. Bridging anticoagulation therapy with enoxaparin appears to be
      feasible during this high-risk period for thromboembolism and could shorten the
      length of hospital stay.

PMID- 16449735
TI  - Stress testing in patients with diabetes mellitus: diagnostic and prognostic
      value.

PMID- 16449736
TI  - Diagnosis of myocarditis: death of Dallas criteria.

PMID- 16449737
TI  - Editorial: dialogue.

PMID- 16449738
TI  - Loving-kindness meditation findings not related to baseline differences.

PMID- 16449740
TI  - Commentary on "Factors Contributing to Women's Ability to Maintain a Walking
      Program".

PMID- 16449739
TI  - Factors Contributing to Women's Ability to Maintain a Walking Program.
AB  - PURPOSE: The purpose of this descriptive study is to determine what strategies
      were most helpful for women to begin and maintain a walking program. METHOD: Data
      from the field notes of a randomized clinical trial to promote walking in 97
      women were used for the qualitative analysis discussed in this article. FINDINGS:
      Overall, the majority of participants met the study goal of walking 90 minutes
      per week. CONCLUSIONS: In addition, the participants reported other benefits,
      including becoming more physically fit, mental and emotional satisfaction, and
      stress reduction. Some of the barriers mentioned by participants were personal
      and/or professional obligations, weather, injuries and/or illnesses, and
      psychosocial factors. When benefits outweighed barriers, the participants had
      greater success meeting their walking goals. IMPLICATIONS: Furthermore, the
      participants stated that making time, problem solving, internal motivation, and
      the support of family and/or friends were the most helpful factors in achieving
      their walking goals.

PMID- 16449741
TI  - The process of empowerment: a parish nurse perspective.
AB  - PURPOSE: The purpose of this study is to describe the services of parish nurse
      empowerment, of client empowerment and empowerment outcomes for nurses and
      clients. METHOD: A sample of 28 parish nurses participated in one of three focus
      groups. Based on analysis of qualitative data from focus group discussions,
      empowerment themes were identified for nurses and clients. FINDINGS: Six items
      were identified as sources of parish nurse empowerment and client empowerment.
      CONCLUSION: The study showed that empowerment is a reciprocal process between the
      parish nurse and clients characterized by recognition of a higher power.
      IMPLICATIONS: To practice in a holistic manner, the spiritual dimension of person
      is a critical element of care.

PMID- 16449742
TI  - Commentary on "the process of empowerment: a parish nurse perspective".

PMID- 16449743
TI  - Spirituality, chronic illness, and rural life.
AB  - PURPOSE: The purpose of this article is to report the findings of an exploration
      of the associations among spirituality, hope, depression, social support, and
      well-being in rural dwelling people who have one or more chronic conditions.
      METHOD: A mail survey was completed by 111 rural-dwelling people with chronic
      illness in two rural western states. FINDINGS: Spirituality, hope, depression,
      and social support had overlapping influence on well-being, although spirituality
      was not shown to have an independent effect. Participants reported unexpectedly
      high levels of hope and low levels of depression despite living with chronic
      illness. CONCLUSIONS: Although spirituality did not have an independent effect,
      the group as a whole had active spiritual and religious lives, possibly
      influencing the high levels of hope and low levels of depression found.
      IMPLICATIONS: The positive picture of rural people with chronic illness needs
      further investigation for possible mitigating effects of spirituality on problems
      associated with chronic illness.

PMID- 16449744
TI  - Commentary on "spirituality, chronic illness, and rural life".

PMID- 16449745
TI  - Effects of therapeutic touch on blood hemoglobin and hematocrit level.
AB  - BACKGROUND: Therapeutic Touch (TT) is a widely used complementary therapy. This
      study investigated the effects of TT on hemoglobin and hematocrit level in
      students who were basically healthy. METHOD: The volunteers with a hemoglobin
      level less than 12 grams per deciliter (g/dl) were randomly assigned to three
      groups of TT, mimic therapeutic touch (MT), and control. Blood samples were
      collected before the first treatment and again a week after the last one and
      measurements were taken. RESULTS: TT increased the level of hemoglobin (.99 .13
      g/dl) and hematocrit (2.82 .43%) significantly. MT also increased the level of
      hemoglobin (.55 .11 g/dl) and hematocrit (2.75 .44%) significantly. No
      significant changes were found in the control group. TT increased hemoglobin more
      effectively than MT (p< .05). CONCLUSIONS: Significant changes of both variables
      in TT and MTgroups suggest that more careful precision might be needed while
      selecting individuals as sham therapists in further experiments.

PMID- 16449746
TI  - Commentary on "effects of therapeutic touch on blood hemoglobin and hematocrit
      level".

PMID- 16449748
TI  - Commentary on "canine visitation (pet) therapy: pilot data on decreases in child
      pain perception".

PMID- 16449747
TI  - Canine visitation (pet) therapy: pilot data on decreases in child pain
      perception.
AB  - PURPOSE: To explore the effectiveness of canine visitation therapy (CVT) in
      pediatric pain management in a tertiary care children's hospital, a descriptive
      pilot study was conducted. METHOD: A convenience sample of 25 English-speaking
      children ages 5 to 18 years who underwent surgery and experienced acute
      postoperative pain participated in a standard, one-time CVT intervention. Each
      child completed a pre-post survey and a post intervention interview. FINDINGS:
      Quantitative pre-post findings indicate that CVT significantly reduced perceived
      pain. Qualitative findings suggest that one mechanism that makes CVT effective
      may be cognitive. That is, CVTdistracts children from pain-related cognition and
      possibly activates comforting thoughts regarding companionship or home.
      CONCLUSION: The study findings suggest that CVT may be a useful adjunct to
      traditional pain management for children. IMPLICATIONS: Nurses may better serve
      their patients when CVT is an option.

PMID- 16449749
TI  - So, why should I become one?: lessons on becoming a holistic nurse.

PMID- 16449750
TI  - Called to nursing: perceptions of student nurses.
AB  - PURPOSE: This study uncovers reasons students report for wanting to become
      nurses, to quantify those who feel that they are called to nursing, and to learn
      what "being called" means to them. METHOD: A descriptive, cross-sectional survey
      was conducted with all students enrolled in nursing courses at one program in a
      private, faith-based university. FINDINGS: Most students decided to go to nursing
      school while in high school or college and chose nursing because they had a
      desire to help others. The most common personal characteristics they identified
      that will be helpful in nursing were being caring or compassionate. Almost two
      thirds of the students indicated they were "called" by God to become nurses.
      CONCLUSION AND IMPLICATIONS: Findings can help nursing educators and leaders
      determine how to better recruit and retain individuals into the nursing
      profession and how to support and encourage caring and compassionate qualities in
      all nurses.

PMID- 16449751
TI  - Arts in health care: a new paradigm for holistic nursing practice.
AB  - Bringing creativity into health care has opened up a new dimension in nursing.
      Creative interventions have been shown to shorten hospital stays and reduce the
      patient's need for pain medication. In response to these benefits, many major
      medical centers around the world have instituted arts in health care programs.
      Arts in Medicine is one such program that serves hundreds of patients. It was
      established by a nurse at the University of Florida and is directly tied to
      nursing care. Programs like this provide clinical models for nurses who want to
      integrate the arts into their health care practice. This article presents these
      models and discusses ways that nurses can easily implement creative interventions
      into their practice.

PMID- 16449753
TI  - Symptoms underlying unawareness of memory impairment in patients with mild
      Alzheimer's disease.
AB  - Patients with Alzheimer's disease (AD) are often unaware of their cognitive
      impairment. This unawareness might have a multifactorial etiology, including
      impairment of cognitive domains and psychiatric symptoms. We conducted this study
      to determine the factors underlying unawareness of memory impairment (UMI) in
      patients with AD. In 103 patients with mild AD, the UMI was quantified as the
      difference between the patient's self-rating and the rating of the patient's
      caregiver on a standardized memory questionnaire system, the Everyday Memory
      Checklist. We then examined the relationships between UMI and memory, attention,
      language, visuospatial/constructive perception, frontal lobe function, and
      psychiatric symptoms. UMI was positively associated with memory impairment and
      delusions when effects of age, sex, and education were partialled out, suggesting
      that these symptoms are involved in the formation of UMI in the patients. Thus,
      existing treatments for memory impairment and delusions may be beneficial for
      increasing the awareness of mild AD patients of their cognitive impairment.

PMID- 16449754
TI  - Beneficial effect of cholinesterase inhibitor medications on recognition memory
      performance in mild to moderate Alzheimer's disease: preliminary findings.
AB  - Cholinesterase inhibitor (ChEI) medications (ie, donepezil, rivastigmine, and
      galantamine) have been useful in slowing the progression of the mild to moderate
      stages of Alzheimer's disease (AD). Findings supporting this have largely relied
      on a global error score from the Alzheimer's Disease Assessment Scale and have
      not described the nature of the memory problems. We examined this issue by
      comparing learning, recall, and recognition scores among 2 groups of mild to
      moderately demented AD patients. Participants were patients from a memory clinic
      who either were on ChEI treatment (AD+ChEI, n = 14) or had never taken a ChEI (AD
      ChEI, n = 14). Participants underwent a comprehensive neuropsychological
      evaluation, including administration of the CERAD Word List Memory test. Results
      indicated no significant group difference for learning and delayed free recall,
      but the AD+ChEI group had significantly fewer errors than the AD-ChEI group on
      the CERAD Recognition test. Our findings provide preliminary evidence that the
      aspect of memory that is most affected by ChEIs appears to be facilitation of
      retention of new information in memory. The implications of this on clinical care
      and functional abilities as well as future directions are discussed.

PMID- 16449755
TI  - Psychosocial predictors of dementia caregiver desire to institutionalize:
      caregiver, care recipient, and family relationship factors.
AB  - Several factors influence dementia caregiver desire to institutionalize; however,
      little is known about differences in caregivers who desire institutionalization
      versus those who do not. The current study compares predictors of desire to
      institutionalize in dementia caregivers. Seventy-two caregivers completed the
      Desire to Institutionalize Scale (DIS) and several psychosocial measures,
      including burden, dementia knowledge, self-efficacy, depression, health, care
      recipient daily functioning and memory/behavior problems, family functioning, and
      social support. Based on DIS responses, caregivers were divided into No DI versus
      DI groups. DI caregivers had significantly higher burden, greater dementia
      knowledge, more family dysfunction, and decreased social support compared with No
      DI caregivers. Findings emphasize the importance of caregiver and family
      relationship variables in DIS, suggesting potentially modifiable targets for
      caregiver interventions. Dementia knowledge was associated with higher DIS,
      suggesting that educational programs alone may not be helpful to delay
      institutionalization.

PMID- 16449756
TI  - Hippocampal volume is associated with physician-reported acute cognitive deficits
      after electroconvulsive therapy.
AB  - Predicting memory problems in older depressed patients receiving
      electroconvulsive therapy (ECT) is difficult. In this study, hippocampal volume
      and acute memory outcomes were examined in 15 patients following an index course
      of ECT. Smaller hippocampal volume was associated with poorer ECT-related memory
      outcomes. These results add to a growing literature on memory, ECT, and the
      hippocampus. Although the findings are significant, the sample size in the study
      is small, so future studies with more complex modeling of key variables that may
      influence memory are warranted.

PMID- 16449757
TI  - A comparison of depressive mood of older adults in a community, nursing homes,
      and a geriatric hospital: factor analysis of Geriatric Depression Scale.
AB  - The Geriatric Depression Scale (GDS)-15 was used in 607 adults aged 65+ years
      living in a community, nursing homes, and a general hospital to explore
      characteristics of depressive mood in different care settings. Factor analysis of
      GDS-15 extracted 4 factors labeled unhappiness, apathy and anxiety, loss of hope
      and morale, and energy loss. The scale scores labeled unhappiness, apathy and
      anxiety, and loss of hope and morale were negatively correlated with the Barthel
      Index and the Mini-Mental State Examination scores. The results classified the
      depressive patterns into 2 types, one fitting the nursing home residents and the
      other fitting the hospital patients. The dominant factors of the nursing-home
      type were unhappiness and loss of hope and morale, and the hospital type was
      highly related with apathy and anxiety. The results indicate an extended utility
      of the GDS-15 for a deeper understanding of depressive mood in various care
      settings.

PMID- 16449758
TI  - Spatial test for agricultural pesticide "blow-in" effect on prevalence of
      Parkinson's disease.
AB  - The current study used Department of Veteran's Affairs (VA) clinical records,
      State of California pesticide application records, spatial maps of distribution
      of Parkinson's disease patients, and pesticide applications to determine if there
      was evidence for "blow-in" of pesticides as a factor in explaining the prevalence
      of Central Valley Parkinson's disease. The results did not support the hypothesis
      of increasing prevalence of Parkinsonism attributable to wind drift.

PMID- 16449759
TI  - Impaired visual acuity as a risk factor for visual hallucinations in Parkinson's
      disease.
AB  - Pathophysiology of hallucinations in Parkinson's disease is poorly understood.
      This study investigated relationships between visual hallucinations and visual
      acuity. Twenty-six consecutive patients with Parkinson's disease participated in
      this study. Patients were divided into two groups: patients with visual
      hallucinations (VH group) and those without visual hallucinations (no-VH group).
      Unaided and corrected eyesight was evaluated in all patients, and if frequent use
      of prescription glasses or contact lenses was involved, eyesight using these
      lenses was also measured as the patient's own best eyesight. If a patient did not
      use prescription glasses or contact lenses, the patient's own best eyesight was
      defined as the unaided eyesight. Multivariate regression analysis demonstrated
      that agonist use and best eyesight were different after the backward elimination
      method. Visual hallucinations were closely related not to uncorrected eyesight or
      unaided eyesight but to the patient's best eyesight. It is suggested that
      impaired visual acuity is a risk factor for visual hallucinations.

PMID- 16449760
TI  - Frontal assessment battery and brain perfusion image in Parkinson's disease.
AB  - The objective was to compare brain perfusion image using 3-dimensional
      stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine
      single photon emission computed tomography between Parkinson's disease patients
      with a high frontal assessment battery score and those with a low frontal
      assessment battery score. Thirty nondemented patients with Parkinson's disease
      were studied. Patients were divided into 2 groups: a high-scoring group whose
      frontal assessment battery score was 12 or more and a low-scoring group whose
      frontal assessment battery score was 11 or less. The high-scoring group included
      21 patients, and the low-scoring group included 9 patients. They underwent N
      isopropyl-p-123I iodoamphetamine single photon emission computed tomography, and
      we analyzed the data by the 3-dimensional stereotactic surface projection method.
      Results showed that left inferior parietal lobule and left supramarginal gyrus
      perfusion of the low-scoring group were significantly decreased compared with the
      high-scoring group. It is concluded that patients with Parkinson's disease may
      have frontal lobe dysfunction, but the decreased frontal assessment battery score
      may be caused not by progressed frontal lobe dysfunction but by parietal lobe
      dysfunction added to their preexisting frontal lobe impairment.

PMID- 16449761
TI  - Performance monitoring and error processing during a lexical decision task in
      patients with Parkinson's disease.
AB  - To evaluate performance monitoring and error processing during lexical decision
      tasks, event-related potentials (ERPs) obtained by time-locked to correct and
      error responses were studied in 17 Parkinson's disease (PD) patients without
      dementia and 15 healthy elderly participants. The amplitude of error negativity
      (Ne) obtained by averages time-locked to error response was significantly reduced
      in the PD patients, whereas there were no significant differences in the negative
      component for the correct response (Nc) between the two participant groups. The
      amplitude of the error positivity (Pe) and correct positivity (Pc) after the Ne
      and Nc components was also significantly reduced in the PD patients. The PD
      patients showed significantly slower reaction times and higher error rates. The
      reduced amplitude of the Ne, Pe, and Pc components in the PD patients suggested
      impaired performance and conflict monitoring as well as abnormal response
      strategy adjustments and deviant in later error monitoring processes associated
      with emotional, conscious evaluation of the error.

PMID- 16449762
TI  - Agpat6--a novel lipid biosynthetic gene required for triacylglycerol production
      in mammary epithelium.
AB  - In analyzing the sequence tags for mutant mouse embryonic stem (ES) cell lines in
      BayGenomics (a mouse gene-trapping resource), we identified a novel gene, 1
      acylglycerol-3-phosphate O-acyltransferase (Agpat6), with sequence similarities
      to previously characterized glycerolipid acyltransferases. Agpat6's closest
      family member is another novel gene that we have provisionally designated Agpat8.
      Both Agpat6 and Agpat8 are conserved from plants, nematodes, and flies to
      mammals. AGPAT6, which is predicted to contain multiple membrane-spanning
      helices, is found exclusively within the endoplasmic reticulum (ER) in mammalian
      cells. To gain insights into the in vivo importance of Agpat6, we used the Agpat6
      ES cell line from BayGenomics to create Agpat6-deficient (Agpat6-/-) mice. Agpat6
      /- mice lacked full-length Agpat6 transcripts, as judged by northern blots. One
      of the most striking phenotypes of Agpat6-/- mice was a defect in lactation. Pups
      nursed by Agpat6-/- mothers die perinatally. Normally, Agpat6 is expressed at
      high levels in the mammary epithelium of breast tissue, but not in the
      surrounding adipose tissue. Histological studies revealed that the aveoli and
      ducts of Agpat6-/- lactating mammary glands were underdeveloped, and there was a
      dramatic decrease in the size and number of lipid droplets within mammary
      epithelial cells and ducts. Also, the milk from Agpat6-/- mice was markedly
      depleted in diacylglycerols and triacylglycerols. Thus, we identified a novel
      glycerolipid acyltransferase of the ER, AGPAT6, which is crucial for the
      production of milk fat by the mammary gland.

PMID- 16449763
TI  - Shotgun lipidomics of cardiolipin molecular species in lipid extracts of
      biological samples.
AB  - Cardiolipin is a prominent component of the mitochondrial inner membranes
      contributing to the regulation of multiple discrete mitochondrial functions.
      Here, we extend shotgun lipidomics to identify and quantitate cardiolipin
      molecular species directly from lipid extracts of biological samples. Three
      shotgun lipidomics approaches for analyses of cardiolipin molecular species were
      developed using either a continuous ion-transmission instrument (i.e., triple
      quadrupole type) with either low or high mass resolution settings or a high mass
      resolution hybrid pulsed instrument [i.e., quadrupole time-of-flight (QqTOF)
      type]. Three chemical principles were used for the development of these
      approaches. These include the marked enrichment of linoleate in cardiolipin to
      maximize the signal-to-noise ratio, the specific neutral loss of ketenes from
      doubly charged cardiolipin molecular ions to yield doubly charged triacyl
      monolysocardiolipins, and the doubly charged character of two phosphates in each
      cardiolipin molecular species. Through these techniques, we identified and
      quantified the specific molecular species profiles of cardiolipin directly from
      lipid extracts of mouse heart, liver, and skeletal muscle. The accuracy (
      approximately 5%) and the low end of the linear dynamic range (10 fmol/microl)
      for quantitation make these approaches useful for studying alterations in
      cardiolipin metabolism in multiple disease states using either type of mass
      spectrometer.

PMID- 16449765
TI  - Medical professionalism: out with the old and in with the new.

PMID- 16449766
TI  - Life threatening abdominal complications following cocaine abuse.

PMID- 16449767
TI  - Walking the walk.

PMID- 16449768
TI  - Huntington disease.

PMID- 16449769
TI  - Hysteria.

PMID- 16449770
TI  - Super hospitals.

PMID- 16449771
TI  - History of brucellosis.

PMID- 16449772
TI  - Walking the walk.

PMID- 16449773
TI  - Semmelweis and his thesis.

PMID- 16449774
TI  - Death to some cliches.

PMID- 16449775
TI  - Death to all cliches?

PMID- 16449777
TI  - The public health agenda and minority ethnic health: a reflection on priorities.

PMID- 16449776
TI  - Modernizing medical careers: an open letter to Royal College Presidents.

PMID- 16449778
TI  - The polymerase chain reaction patents: going, going,... still going.

PMID- 16449780
TI  - The doctor's PDA and Smartphone Handbook: the task list.

PMID- 16449779
TI  - Research governance: ethical issues.
AB  - Healthcare research is haunted by a history of unethical studies in which
      profound harm was caused to vulnerable individuals. Official systems for gaining
      ethical approval for research, designed to prevent a repetition of these shameful
      examples, can prove bureaucratic and inflexible in practice. The core ethical
      principles of respect for autonomy, prevention of harm, promotion of benefit, and
      justice (which form the basis of professional codes of research conduct) must be
      applied flexibly to take account of contextual, methodological, personal and
      practical considerations. Ensuring that the design and conduct of all research is
      ethically sound is the responsibility of all involved-including researchers,
      research institutions, ethics review committees and regulatory bodies.

PMID- 16449781
TI  - Bullous disease of the lung and cannabis smoking: insufficient evidence for a
      causative link.

PMID- 16449783
TI  - Ruptured ectopic pregnancy after a decline in chorionic gonadotropin.

PMID- 16449782
TI  - Association of population and practice factors with potentially avoidable
      admission rates for chronic diseases in London: cross sectional analysis.
AB  - OBJECTIVES: To examine the association between underlying ill health, material
      deprivation and primary care supply factors and hospital admission rates for
      potentially avoidable admissions in primary care trusts in London. DESIGN: Cross
      sectional analysis at primary care trusts level using routine data from multiple
      sources. SETTING: All 31 primary care trusts in London with a total resident
      population of 7 million patients. MAIN OUTCOME MEASURES: Age-standardized
      hospital admission rates for asthma, diabetes, heart failure, hypertension and
      chronic obstructive pulmonary disease. RESULTS: Admission rates varied widely for
      the conditions examined across the 31 primary care trusts. In 2001, age adjusted
      admission rates for asthma varied from 76 to 189 per 100,000 and for diabetes
      from 38 to 183 per 100,000. There was a significant association between higher
      admission rates and measures of underlying ill health and material deprivation
      but not quantitative measures of primary care service provision. Provision of
      specialist chronic disease services in primary care for diabetes but not for
      asthma were significantly associated with reduced admission rates. There was no
      association of prescribing levels in primary care trusts with admission rates for
      any of the conditions examined. CONCLUSIONS: Although hospital admission for some
      chronic diseases is potentially avoidable and rates of hospital admission for
      these conditions are possible indicators of the quality of care, they should be
      interpreted in conjunction with measures of population composition and
      deprivation. Failure to do this may result in primary care trusts and general
      practitioners being criticized for aspects of health care utilization that are
      not under their direct control.

PMID- 16449784
TI  - Bilateral chronic subdural haematoma: a reversible cause of parkinsonism.

PMID- 16449785
TI  - Down and almost out in Scotland: George Orwell, tuberculosis and getting
      streptomycin in 1948.

PMID- 16449786
TI  - Confidentiality versus public duty.

PMID- 16449787
TI  - Postdocs without borders: science goes global.

PMID- 16449789
TI  - Response to C3a, mast cells, and asthma.

PMID- 16449790
TI  - Statins, cholesterol, and the prevention of coronary heart disease.

PMID- 16449791
TI  - Diverse membrane-associated proteins contain a novel SMP domain.
AB  - We have analyzed the sequence of a mitochondrial integral membrane protein,
      Mdm12, and found that it forms the prototype for a novel domain, designated the
      SMP domain, that is common to an extended family of membrane-associated proteins.
      Comprehensive sequence searches using protein alignment models of SMP proteins
      were cross-validated by statistical resampling; providing strong support for
      these relationships. No consensus of 3-dimensional structure was reached upon
      threading sequences through known folds. SMP proteins are widespread amongst
      eukaryotic species with a particular enrichment in plants and features suggestive
      of species-specific functional variations. Members of 2 SMP families, the
      mitochore and tricalbin proteins, are essential components of protein complexes
      involved in mitochondrial inheritance and receptor endocytosis while a third SMP
      protein family, HT008, is associated with the Rvs161-Rvs167 complex, a known
      regulator of sphingolipid metabolism. In addition, HT008 and PDZK8 SMP proteins
      possess additional protein-protein interaction domains in domain architectures
      that are typical of protein scaffolds and adaptors. We therefore predict that the
      SMP domain is an important link between these distinct membrane-associated
      proteins and a key regulatory hub for unidentified global regulators.-Lee, I.,
      Hong, W. Diverse membrane-associated proteins contain a novel SMP domain.

PMID- 16449793
TI  - Local extravascular pool of C3 is a determinant of postischemic acute renal
      failure.
AB  - The third complement component (C3) is an acute phase protein that plays a
      central role in reperfusion injury in several organ models. To investigate the
      contribution of local synthesis of C3 and distinguish it from that of circulating
      complement mainly produced by hepatic synthesis, we employed a mouse renal
      isograft model. Our model demonstrated a close relationship between the extent of
      intrarenal expression of C3 and cold-ischemia induced injury. Ischemic C3
      positive donor kidneys transplanted into C3-positive or C3-negative recipients
      developed widespread tissue damage and severe acute renal failure. In contrast,
      ischemic C3-negative isografts exhibited only mild degrees of functional and
      structural disturbance, even when transplanted into normal C3-positive
      recipients. Thus local synthesis of C3, mostly identified in the tubular
      epithelium, was essential for complement-mediated reperfusion damage, whereas
      circulating C3 had a negligible effect. Our results suggest a two-compartment
      model for the pathogenic function of C3, in which the extravascular compartment
      is the domain of local synthesis of C3, and where the role of circulating C3 is
      redundant. Our data cast new light on the mechanism of complement-mediated tissue
      injury in nonimmunological disorders, and challenges the longstanding dogma that
      circulating components are the main complement effectors of extravascular tissue
      damage.

PMID- 16449792
TI  - Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores
      ventricular function.
AB  - We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1
      (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after
      acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on
      postinfarction recovery has not been investigated. In the current study, we
      assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV)
      remodeling and function using echocardiographic imaging and histomorphometric
      approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11)
      particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene
      transfer, the animals were subjected to 30 min of ischemia by ligation of left
      anterior descending artery (LAD) followed by reperfusion. Echocardiographic
      measurements were obtained in a blinded fashion prior and at 1.5 and 3 months
      after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ
      groups, respectively at 1.5 months after MI. Three months after MI, EF recovered
      fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV
      dimensions were markedly increased and the anterior wall was markedly thinned in
      the LacZ-treated animals compared with the HO-1-treated animals. Significant
      myocardial scarring and fibrosis were observed in the LacZ-group in association
      with elevated levels of interstitial collagen I and III and MMP-2 activity. Post
      MI myofibroblast accumulation was reduced in the HO-1-treated animals, and
      retroviral overexpression of HO-1 reduced proliferation of isolated cardiac
      fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces
      fibrosis and ventricular remodeling and restores LV function and chamber
      dimensions after myocardial infarction.

PMID- 16449795
TI  - Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP
      transgenic mice model.
AB  - Familial amyloidotic polyneuropathy is an autosomal dominant disorder mainly
      characterized by the extracellular deposition of transthyretin, with special
      involvement of the peripheral nerve. Several animal models have been generated,
      including transgenic mice carrying the most prevalent TTR mutation (TTR
      Val30Met). TTR-Val30Met mice without endogenous TTR (TTR-Val30Met X TTR-KO) were
      previously analyzed in our laboratory and approximately 60% of the animals over 1
      year of age were found to have deposition as amyloid, i.e., with Congo red (CR) 
      positive material, constituting a good tool to investigate the effect of drugs on
      TTR deposition and fibrillogenesis. We recently showed that the drug doxycycline
      acts in vitro as a TTR fibril disrupter. In the present work we assessed the
      activity of this drug in vivo in the TTR-Met30Val X TTR-KO mice. Doxycycline was
      administrated in the drinking water to 23- to 28-month-old mice over a period of
      3 months. Immunohistochemistry analyses revealed no differences in nonfibrillar
      TTR deposition between treated (n=11) and untreated mice (n=11). However, CR
      positive material was observed only in the control group (untreated) whereas none
      of the animals treated with doxycycline was CR-positive. Immunohistochemistry for
      several markers associated with amyloid, such as matrix metalloproteinase-9 (MMP
      9) and serum amyloid P component (SAP), was performed. MMP-9 was altered with
      significantly lower levels in treated animals compared with the control group.
      Mouse SAP was absent in treated animals, being observed only in untreated animals
      presenting TTR congophilic deposits. These results indicate that doxycycline is
      capable of disrupting TTR CR-positive amyloid deposits and decreases standard
      markers associated with fibrillar deposition, being a potential drug in the
      treatment of amyloidosis.

PMID- 16449794
TI  - The C. elegans pvf-1 gene encodes a PDGF/VEGF-like factor able to bind mammalian
      VEGF receptors and to induce angiogenesis.
AB  - Members of the platelet-derived growth factor/vascular endothelial growth factor
      (PDGF/VEGF) family have been implicated in a variety of functions in vertebrates,
      especially angiogenesis. Here we identify and characterize a PDGF/VEGF-like
      factor (named PVF-1) from the nematode C. elegans. We show that PVF-1 has
      biochemical properties similar to vertebrate PDGF/VEGF growth factors. More
      important, PVF-1 binds to the human receptors VEGFR-1 (Flt-1) and VEGFR-2 (KDR)
      and is able to induce angiogenesis in two model systems derived from vertebrates.
      Our results highlight the widespread evolutionary conservation of this important
      class of growth factors and raise the possibility that C. elegans can provide a
      simple experimental system in which to investigate how these factors function.

PMID- 16449796
TI  - Chordin is underexpressed in ovarian tumors and reduces tumor cell motility.
AB  - Ovarian cancers mostly derive from the monolayer epithelium that covers the
      ovary. There are currently very few molecular clues to the etiology of this
      cancer. Bone morphogenetic proteins (BMPs) are required for follicular
      development and female fertility and are expressed in the ovarian surface
      epithelium (OSE). We previously reported the expression of human chordin (CHRD),
      a BMP extracellular regulator, in the ovary. Here we show that CHRD is
      underexpressed in epithelium ovary cancer and epithelial cancer cell lines as
      compared with normal tissues and OSE, respectively. Besides, we detected BMP
      expression in all ovarian cell lines analyzed. To determine the functional
      relevance of the absence of CHRD mRNA in tumors and cancer cell lines, we studied
      the effects of CHRD on two cancer cell lines, BG1 and PEO14. Migratory and
      invasive properties were greatly reduced, whereas cell adhesion to the support
      was enhanced. In addition, we detected chordin (Chrd) expression in OSE of rat
      ovaries in a pattern similar to that of BMP4. Altogether, these results suggest
      that CHRD could participate in regulating BMP activity in normal OSE physiology,
      and that its mis-expression in OSE may facilitate cancer incidence and/or
      progression.

PMID- 16449797
TI  - Potent regulation of microglia-derived oxidative stress and dopaminergic neuron
      survival: substance P vs. dynorphin.
AB  - Unregulated microglial activation has been implicated as a pivotal factor
      contributing to Parkinson's disease. Using mesencephalic neuron-glia cultures, we
      address the novel possibility that peptides endogenous to the substantia nigra
      (SN), substance P and dynorphin (10(-13)-10(-14) M), are opposing mediators of
      microglial activation and consequent DA neurotoxicity. Here, we identify that
      substance P (10(-13)-10(-14) M) is selectively toxic to DA neurons in a microglia
      dependent manner. Mechanistically, substance P (10(-13)-10(-14) M) activated
      microglial NADPH oxidase to produce extracellular superoxide and intracellular
      reactive oxygen species (ROS). Neuron-glia cultures from mice lacking a
      functional NADPH oxidase complex (PHOX-/-) were insensitive to substance P (10(
      13)-10(-14) M) -induced loss of DA neuron function. Mixed glia cultures from
      (PHOX-/-) mice failed to show a significant increase in intracellular ROS in
      response to substance P compared with control cultures (PHOX+/+). Further,
      dynorphin (10(-14) M) inhibited substance P (10(-13) M) -induced loss of [3H] DA
      uptake. Here we demonstrate a tightly regulated mechanism governing microglia
      derived oxidative stress, where the neuropeptide balance of dynorphin and
      substance P is critical to DA neuron survival.

PMID- 16449799
TI  - Protective effect of melatonin against mitochondrial dysfunction associated with
      cardiac ischemia- reperfusion: role of cardiolipin.
AB  - Reactive oxygen species (ROS) are considered an important factor in
      ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration,
      mainly at the level of complex I and III, is an important source of ROS
      generation and hence a potential contributor of cardiac reperfusion injury.
      Appropriate antioxidant strategies could be particularly useful to limit this ROS
      generation and associated mitochondrial dysfunction. Melatonin has been shown to
      effectively protect against ischemic-reperfusion myocardial damage. The mechanism
      by which melatonin exerts this cardioprotective effect is not well established.
      In the present study we examined the effects of melatonin on various parameters
      of mitochondrial bioenergetics in a Langerdoff isolated perfused rat heart model.
      After isolation of mitochondria from control, ischemic-reperfused and melatonin
      treated ischemic-reperfused rat heart, various bioenergetic parameters were
      evaluated such as rates of mitochondrial oxygen consumption, complex I and
      complex III activity, H2O2 production as well as the degree of lipid
      peroxidation, cardiolipin content, and cardiolipin oxidation. We found that
      reperfusion significantly altered all these mitochondrial parameters, while
      melatonin treatment had strong protective effect attenuating these alterations.
      This effect appears to be due, at least in part, to the preservation, by ROS
      attack, of the content and integrity of cardiolipin molecules which play a
      pivotal role in mitochondrial bioenergetics. Protection of mitochondrial
      dysfunction was associated with an improvement of post-ischemic hemodynamic
      function of the heart. Melatonin had also strong protective effect against
      oxidative alterations to complex I and III as well as to cardiolipin in isolated
      mitochondria.

PMID- 16449800
TI  - Extracellular ATP-stimulated current in wild-type and P2X4 receptor transgenic
      mouse ventricular myocytes: implications for a cardiac physiologic role of P2X4
      receptors.
AB  - P2X receptors, activated by extracellular ATP, may be important in regulating
      cardiac function. The objective of the present study was to characterize the
      electrophysiologic actions of P2X4 receptors in cardiac myocytes and to determine
      whether they are involved in mediating the effect of extracellular ATP. Membrane
      currents under voltage clamp were determined in myocytes from both wild-type (WT)
      and P2X4 receptor-overexpressing transgenic (TG) mice. The P2X agonist 2-meSATP
      induced an inward current at -100 mV that was greater in magnitude (2-fold) in TG
      than in WT ventricular cells. In the presence of the P2X4 receptor-selective
      allosteric enhancer ivermectin (3 microM), the 2-meSATP-stimulated current
      increased significantly in both WT and TG ventricular cells, consistent with an
      important role of P2X4 receptors in mediating the ATP current not only in TG but
      also WT myocytes. That the current in both WT and TG cells showed similar voltage
      dependence and reverse potential (approximately 0 mV) further suggests a role for
      this receptor in the normal electrophysiological action of ATP in WT murine
      cardiac myocytes. The P2X antagonist suramin was only able to block partially the
      2-meSATP-stimulated current in WT cells, implying that both P2X4 receptor and
      another yet-to-be-identified P2X receptor mediate this current.

PMID- 16449801
TI  - Control of APP processing and Abeta generation level by BACE1 enzymatic activity
      and transcription.
AB  - Deposition of amyloid beta protein (Abeta) is one of the characteristic features
      of Alzheimer's disease (AD) neuropathology. Beta-secretase, a beta-site APP
      cleaving enzyme 1 (BACE1), is essential for Abeta biosynthesis. Although
      inhibition of BACE1 is considered a valid therapeutic target for AD, the
      enzymatic dynamics of BACE1 in regulating APP processing and Abeta generation has
      not yet been fully defined. To examine this issue, tightly controlled inducible
      BACE1 gene expression was established in the neuronal cell line N2ABP1 and the
      non-neuronal cell line E2BP1 using an ecdysone-inducible system. The BACE1
      protein level was increased in a time- and dosage-dependent manner in the
      inducible BACE1 stable cells by treatment with inducer ponasterone A. The
      generation of APP CTFbeta, the beta-secretase product, increased proportionally
      with the level of BACE1 protein expression. However, Abeta40/42 production
      sharply increased to the plateau level with a relatively small increase in BACE1
      expression. Although further increasing BACE1 expression increased beta-secretase
      activity, it had no additional effect on Abeta production. Furthermore, we found
      that BACE1 mRNA levels and BACE1 promoter activity were significantly lower than
      APP mRNA levels and APP promoter activity. Our data demonstrate that lower BACE
      transcription is responsible for the minority of APP undergoing the amyloidogenic
      pathway and relatively lower Abeta production in the normal conditions, and that
      a slight increase in BACE1 can induce a dramatic elevation in Abeta production,
      indicating that the increase in BACE1 can potentially increase neuritic plaque
      formation in the pathological condition.

PMID- 16449798
TI  - Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity
      in livers of aged and long-lived Snell dwarf mice.
AB  - We have proposed that the age-associated increase of reactive oxygen species
      (ROS) by electron transport chain (ETC) dysfunction may cause the elevated basal
      level of p38 MAPK stress response pathway activity. However, the mechanism by
      which ROS activates this pathway is not clear. Here we propose that activation of
      the p38 MAPK pathway by complex I (CI) generated ROS, in response to rotenone
      (ROT) treatment, is based on the ability of reduced Trx to bind to and inhibit
      ASK 1 and its release from the complex upon oxidation. This balance of free vs.
      bound ASK1 regulates the level of p38 MAPK pathway activity. To support this
      mechanism we demonstrate that the production of ROS by ROT treated AML12
      hepatocyte cells dissociates the Trx-ASK1 complex, thereby increasing p38 MAPK
      pathway activity. This mechanism is supported by the ability of N-acetyl cysteine
      (NAC) to prevent dissociation of Trx-ASK1 and activation of the p38 MAPK pathway.
      We also demonstrated that the ratio of ASK1/Trx-ASK1 increases in aged mouse
      livers and that this correlates with the increased basal activity of the p38 MAPK
      pathway. The longevity of Snell dwarf mice has been attributed to their
      resistance to oxidative stress. A comparison of the levels of Trx-ASK1 in young
      and aged dwarfs showed a higher abundance of the complex than in their age
      matched controls. These results, which are indicative of a decreased level of
      oxidative stress, suggest that increased ROS production in aged liver may alter
      the ratio of ASK1 and Trx-ASK1, thereby increasing the age-associated basal level
      of p38 MAPK pathway activity.

PMID- 16449802
TI  - Phosphorylation and protonation of neighboring MiRP2 sites: function and
      pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis.
AB  - MinK-related peptide 2 (MiRP2) and Kv3.4 subunits assemble in skeletal muscle to
      create subthreshold, voltage-gated potassium channels. MiRP2 acts on Kv3.4 to
      shift the voltage dependence of activation, speed recovery from inactivation,
      suppress cumulative inactivation and increase unitary conductance. We previously
      found an R83H missense mutation in MiRP2 that segregated with periodic paralysis
      in two families and diminished the effects of MiRP2 on Kv3.4. Here we show that
      MiRP2 has a single, functional PKC phosphorylation site at serine 82 and that
      normal MiRP2-Kv3.4 function requires phosphorylation of the site. The R83H
      variant does not prevent PKC phosphorylation of neighboring S82; rather, the
      change shifts the voltage dependence of activation and endows MiRP2-Kv3.4
      channels with sensitivity to changes in intracellular pH across the physiological
      range. Thus, current passed by single R83H channels decreases as internal pH is
      lowered (pK(a) approximately 7.3, consistent with histidine protonation) whereas
      wild-type channels are largely insensitive. These findings identify a key
      regulatory domain in MiRP2 and suggest a mechanistic link between acidosis and
      episodes of periodic paralysis.

PMID- 16449803
TI  - Distribution of costameric proteins in the diaphragm of patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with an
      increased load on the diaphragm. Increased (eccentric) loading has been shown to
      result in disturbances in the cytoskeleton. OBJECTIVES: We hypothesized that due
      to a continuous overload of the diaphragm in COPD patients, distinct alterations
      in the membrane-associated cytoskeleton occur, especially in the costameres.
      METHODS: Diaphragm biopsies from 7 COPD patients (forced expiratory volume in 1 s
      62 +/- 3% predicted) and 5 non-COPD patients (forced expiratory volume in 1 s 105
      +/- 6% predicted) were obtained. Cryosections of these biopsies were stained with
      antibodies against the costameric proteins of the focal adhesion complex
      (vinculin, talin and integrin-beta(1)), the dystroglycan complex (dystrophin and
      beta-dystroglycan) and the spectrin-based membrane cytoskeleton (beta-spectrin).
      Furthermore, in these cryosections, the basal membrane protein laminin was
      stained. RESULTS: We found no differences in the distribution and staining
      intensity of the costameric proteins of the focal adhesion complex, the
      dystroglycan complex and the spectrin-based membrane cytoskeleton in the
      diaphragm between the COPD and the non-COPD patients. Furthermore, no differences
      were observed in the expression of laminin in the diaphragm between COPD and non
      COPD patients. CONCLUSIONS: These results indicate that the increased loading to
      which the diaphragm is exposed in COPD does not result in disturbances in
      expression of the costameric system and histological damage of the sarcolemma.

PMID- 16449804
TI  - Drug-induced pneumonitis associated with imatinib mesylate in a patient with
      idiopathic pulmonary fibrosis.
AB  - A 74-year-old man with idiopathic pulmonary fibrosis (IPF) developed severe
      dyspnea on exertion after the readministration of imatinib mesylate for chronic
      myeloid leukemia. Chest X-ray and CT showed ground-glass opacities in both lungs
      in addition to preexisting honeycombing. Discontinuation of imatinib and
      methylprednisolone pulse therapy followed by administration of oral prednisolone
      resulted in improvement in both symptoms and radiographic findings. Imatinib
      induced pneumonitis was diagnosed based on the clinical course and findings. Only
      five previous reports of imatinib-induced pneumonitis have been published in the
      literature, and this is the first case reported in a patient with IPF.

PMID- 16449805
TI  - Sudden sensorineural hearing loss: evidence from Taiwan.
AB  - OBJECTIVE: This study uses 5-year population data to determine the incidence rate
      of sudden sensorineural hearing loss (SSNHL) in Taiwan, taking into consideration
      the age and gender of patients, as well as seasonal variations. STUDY DESIGN: A
      retrospective cross-sectional study. METHOD: The data used is from the Taiwan
      National Health Insurance Research Database covering the period from 1998 to
      2002. A total of 9,267 sample patients were identified from the database by a
      principal diagnosis of unspecified sudden hearing loss (ICD-9-CM code 3882). The
      autoregressive integrated moving average (ARIMA) method was also carried out in
      order to identify any variations in the monthly incidence rates of SSNHL.
      RESULTS: We find that for the period under examination, gender-specific incidence
      rates per 100,000 of the population were 8.85 for males, and 7.79 for females,
      and that there was an increase in age-specific SSNHL incidence with age. The
      ARIMA test for seasonality was found to be significant for the whole sample. Of
      all the seasons in Taiwan, the highest SSNHL incidence rates were found in
      autumn. CONCLUSIONS: Our finding of significant variations in the monthly
      incidence of SSNHL provides valuable information for otolaryngologists and public
      health officials, creating an awareness of periods of a potential increased risk
      of SSNHL.

PMID- 16449806
TI  - Identification of a novel mutation in the myosin VIIA motor domain in a family
      with autosomal dominant hearing loss (DFNA11).
AB  - We ascertained a large Italian family with an autosomal dominant form of non
      syndromic sensorineural hearing loss with vestibular involvement. A genome-wide
      scan found linkage to locus DFNA11. Sequencing of the MYO7A gene in the linked
      region identified a new missense mutation resulting in an Ala230Val change in the
      motor domain of the myosin VIIA. Myosin VIIA has already been implicated in
      several forms of deafness, but this is the third mutation causing a dominant form
      of deafness, located in the myosin VIIA motor domain in a region never involved
      in hearing loss until now. A modelled protein structure of myosin VII motor
      domain provides evidence for a significant functional effect of this missense
      mutation.

PMID- 16449808
TI  - Disappearance of microembolic signals after heparin in acute cerebral ischemia
      due to cyanotic heart disease with polyglobulia.

PMID- 16449807
TI  - Stroke prevention using the oral direct thrombin inhibitor ximelagatran in
      patients with non-valvular atrial fibrillation. Pooled analysis from the SPORTIF
      III and V studies.
AB  - BACKGROUND: To show results of a prespecified pooled analysis of the studies
      SPORTIF III (open-label) and SPORTIF V (double-blind), to assess the homogeneity
      of the results and to explore subgroup analyses and adverse events. METHODS AND
      RESULTS: 7,329 patients with atrial fibrillation (AF) and >or=1 additional stroke
      risk factor were randomized to warfarin (international normalized ratio 2.0-3.0)
      or ximelagatran (36 mg twice daily). Over 11,346 patient-years (mean 18.5
      months/patient), 184 patients developed primary events of stroke and systemic
      embolism (ximelagatran 1.62 vs. warfarin 1.65%/year; p = 0.94). Heterogeneity
      between trials with respect to the primary event rate (study-by-treatment
      interaction p = 0.026) was found. This could not be explained statistically by
      baseline patient characteristics or by treatment (except perhaps by the better
      anticoagulation with warfarin in SPORTIF V) and was not evident for secondary end
      points. There was no conclusive difference in major bleeding rates (ximelagatran
      1.88 vs. warfarin 2.46%/year; p = 0.054), but combined minor plus major bleeding
      was lower with ximelagatran (31.7 vs. 38.7%/year; p < 0.0001). Elevation of liver
      enzymes occurred more frequently in patients taking ximelagatran (6.1% vs.
      warfarin 0.8%; p < 0.0001) and was reversible except in rare cases. CONCLUSIONS:
      Fixed-dose oral ximelagatran without coagulation monitoring prevented stroke and
      systemic embolism as effectively as warfarin in patients with AF. Differences in
      the results of the two trials might relate to consistency of warfarin
      anticoagulation, different degree of blinding in the two trials, other
      concomitant therapies or chance. Further investigation is required to explore the
      long-term safety profile of ximelagatran.

PMID- 16449809
TI  - What is the best choice for combination therapy in the management of dyslipidemia
      of metabolic syndrome?

PMID- 16449811
TI  - Left ventricular hypertrabeculation/noncompaction with PMP22 duplication-based
      Charcot-Marie-Tooth disease type 1A.
AB  - A 50-year-old women with Charcot-Marie-Tooth hereditary neuropathy type 1A due to
      the PMP22 duplication on chromosome 17p11.2-12 developed a left bundle branch
      block and progressive dilatation of the left ventricle since age 40 years and
      recurrent heart failure since age 44 years. At age 50 years left ventricular
      hypertrabeculation/noncompaction was first recognized on transthoracic
      echocardiography. A possible causal relation between the cardiac abnormalities
      and the PMP22 duplication is discussed.

PMID- 16449812
TI  - QT interval prolongation and Torsades de Pointes in a patient receiving zolpidem
      and amiodarone.

PMID- 16449813
TI  - Letter from Konstantinos P. Letsas et al. - invited editorial comment.

PMID- 16449814
TI  - An evaluation of ECG leads used to assess QT prolongation.
AB  - AIMS: The aim of the present study is to elucidate the optimal lead to be
      selected for the evaluation of drug-induced QT prolongation. METHODS AND RESULTS:
      We assessed the validity of each electrocardiography (ECG) lead for the
      evaluation of QT intervals in 688 patients receiving psychotropic drugs. Abnormal
      QTc prolongation was observed in 96 (14%) patients using the longest ECG lead.
      Prevalence of QTc prolongation was larger when using leads I, III, aVR, aVL, aVF,
      V1, and V6 (> 18%), and smaller when using lead V2 (10%). In the remaining 4 ECG
      leads, the overall accuracy to predict QTc prolongation was higher when using
      lead V3 (94%) compared with lead II (89%) or lead V5 (90%). Sensitivity to
      predict QTc prolongation was higher when using lead V4 (81%) compared with lead
      II (66%) or lead V2 (63%). CONCLUSION: When a single lead was used for the
      evaluation of QT prolongation, the results were not always similar to those using
      the lead which demonstrated the longest QT interval, and if only one lead is to
      be chosen, lead V3 or V4 should be selected.

PMID- 16449815
TI  - Increased expression of RANTES, CCR3 and CCR5 in the lesional skin of patients
      with atopic eczema.
AB  - BACKGROUND: Atopic eczema (AE) is a relapsing inflammatory disease based on IgE
      sensitization and characterized by peripheral blood eosinophilia and eosinophil
      infiltration into the lesional skin. In the patch test reaction of AE by
      allergens, an increased infiltration of activated eosinophils has been
      demonstrated peaking at 24-48 h. Regulated on activation normal T cell expressed
      and secreted (RANTES/CCL5) is a chemokine that induces eosinophil migration, and
      CCR3 and CCR5 are the receptors of RANTES. OBJECTIVE: In order to further clarify
      the pathomechanisms of eosinophil infiltration in ongoing chronic inflammation in
      the skin of patients with AE and its relation to disease severity, we examined
      the expression of RANTES and its receptors CCR3 and CCR5 in challenged and
      unchallenged lesional skin of AE. METHODS: We examined the number of RANTES+
      cells, CCR3+ cells, CCR5+cells, activated (EG2+) eosinophils and CD3+ T cells in
      normal skin of healthy volunteers, and in challenged lesional skin (24 h after
      mite patch test) as well as unchallenged lesional skin of AE patients by
      immunohistochemistry. The cellular source of RANTES, CCR3 and CCR5 was analyzed
      by double immunohistochemistry using specific antibodies to RANTES, CCR3 or CCR5,
      and antibodies to ECP (EG2) or CD3. RESULTS: The numbers of RANTES+ cells, CCR3+
      cells, CCR5+ cells, EG2+ cells and CD3+ cells were all significantly increased in
      challenged (mite patch-tested) lesional skin of AE patients as compared to those
      in unchallenged lesional skin and normal skin. The numbers of these cells in
      unchallenged lesional skin were greater than those in normal skin. The number of
      EG2+ cells in the unchallenged lesional skin correlated with both the peripheral
      blood eosinophil count and the SCORAD index. The number of EG2+ cells in
      challenged lesional skin correlated with the number of CCR5+ cells. Activated
      eosinophils and T cells expressed RANTES and various proportions of these cells
      were CCR3+ and CCR5+ in both challenged and unchallenged lesional skin.
      CONCLUSION: Taken together, these results suggest that RANTES as well as its
      receptors CCR3 and CCR5 may play important roles in the orchestration of
      eosinophil infiltration in ongoing chronic inflammation in AE, and also reflect
      the severity of disease.

PMID- 16449816
TI  - Theophylline as 'add-on' therapy to cetirizine in patients with chronic
      idiopathic urticaria. A randomized, double-blind, placebo-controlled pilot study.
AB  - BACKGROUND: Chronic urticaria is a prevalent condition associated with
      substantial disability. Its pathogenesis is not clearly understood and is divided
      into autoimmune and chronic idiopathic urticaria (CIU). We investigated if the
      non-specific phosphodiesterase inhibitor theophylline could provide additional
      benefit to the histamine-1 receptor (H-1R) antagonist cetirizine in CIU. METHODS:
      This was a double-blind, placebo-controlled, parallel study. Patients were
      randomized to receive either cetirizine and theophylline (200 mg twice daily;
      group A, 67 subjects) or cetirizine and placebo for 6 months (group B, 67
      subjects). Group A patients took theophylline for 6 more months. Response was
      assessed by visual analog scale (VAS) and treatment effectiveness score (TES).
      Blood theophylline levels were also determined at visit t=1 and t=7. RESULTS: The
      study was completed by 54 of the 67 patients (80.6%) in group A and 51 of the 67
      patients (76.1%) in group B. The physician VAS values for group A were lower
      after t=3, while the patient VAS values were decreased after t=2. The physician
      and patient TES values in group A were statistically higher (p<0.05) at all time
      points except for t=1. At least 1 month of theophylline addition was necessary to
      obtain statistically significant benefit over cetirizine, and reducing
      theophylline by 50% during phase 2 did not alter this benefit. Pruritus values
      were reduced, but not statistically significant. CONCLUSIONS: Addition of
      theophylline to conventional H-1R antagonists was well tolerated without any
      adverse effects and provided considerable additional benefit in the management of
      CIU.

PMID- 16449817
TI  - Elevated tryptase levels are associated with greater bone density in a cohort of
      patients with mastocytosis.
AB  - BACKGROUND: Mastocytosis is associated with a pathological increase in tissue
      mast cells. Associated skeletal problems include a decrease in bone density and
      pathological fractures. METHODS: In order to explore the relationship between
      bone density and the severity of mastocytosis, 21 patients with mastocytosis who
      underwent dual-energy X-ray absorptiometry were entered into this study.
      Correlation coefficients were computed between Z-scores and demographic, clinical
      and laboratory data. Femoral neck Z-scores correlated with serum tryptase levels
      when all the patients were considered (p=0.029). RESULTS AND CONCLUSION: Patients
      with less severe disease had significantly lower values at the L1-L4 spine
      (p=0.046) and femoral neck (p=0.029) Z-scores compared to patients with more
      severe disease. Most patients who had low Z-scores (between -1 and -2.5) were
      under 50 years of age, had less severe disease and had lower serum tryptase
      levels. A history of gastroesophageal reflux disease and a history of hypotensive
      episodes correlated with lower L1-L4 spine Z-scores (p<0.05). Thus, patients with
      less severe disease and lower serum tryptase levels should in particular have
      their bone density determined with treatment appropriate to the findings.

PMID- 16449818
TI  - Intracellular pH as a determinant of vascular smooth muscle function.
AB  - Intracellular pH (pHi) is a physiological parameter that is intimately linked to
      contractility, growth and proliferation of vascular smooth muscle (VSM).
      Regarding contractility, no general unifying concept of pHi regulation but a
      rather complex relation between pHi signals and vascular tone has been revealed
      so far. The modulation of vasotone by pHi depends on the type of blood vessel as
      well as on the pattern of regulatory input signals. In addition, changes in pHi
      have been recognized as an important cellular signal to determine the fate of
      cells in terms of proliferation or apoptosis. Cellular sensors for pHi include a
      variety of ion transport systems which control intracellular Ca2+ gradients and
      are likely to serve as a link between pHi and cell functions. Here we provide an
      overview on the potential targets and mechanisms that transduce pHi signals in
      VSM. The role of pHi-sensing signaling complexes and localized pHi signaling as
      the basis of diversity of pHi regulation of VSM function is discussed.

PMID- 16449821
TI  - Association of the -1438G/A polymorphism of the 5-HT2A receptor gene with
      obstructive sleep apnea syndrome.
AB  - OBJECTIVE: Serotonergic neurons innervating motoneurons increase their firing
      rates in response to respiratory challenges, and long-term facilitation of
      respiratory activity in response to hypoxia is serotonin (5-HT) dependent.
      Polymorphism of the genes which code for 5-HT receptors may affect functions of
      the serotonergic system, and may be associated with obstructive sleep apnea
      syndrome (OSAS). The objective in this study was to assess the significance of
      T102C and -1438G/A polymorphisms of the 5-HT2A receptor gene in OSAS. METHODS:
      Fifty-five patients with OSAS and 102 healthy volun teers were included for
      genetic analyses of T102C and -1438G/A polymorphisms of the 5-HT2A receptor gene.
      RESULTS: For the T102C polymorphism, there was no significant difference between
      the patients and controls and both genders (p > 0.05). For the -1438G/A
      polymorphism, the A/A and G/A genotypes were overrepresented in the patients and
      controls, respectively (p = 0.045). In the control group, the genotypes of both
      genders were not significantly different (p > 0.05). In the patients, the A/A and
      G/A genotypes were overrepresented in males and females, respectively (p =
      0.035). Concerning males, the A/A genotype was overrepresented in patients (p =
      0.007). CONCLUSION: Serotonergic mechanisms appear to be related to OSAS. The
      T102C polymorphism of the 5-HT2A receptor gene is not associated with OSAS.
      However, the -1438G/A polymorphism is associated with OSAS occurrence, especially
      in male patients. This polymorphism may also be associated with different OSAS
      incidences of both genders.

PMID- 16449819
TI  - Secretagogin is a novel marker for neuroendocrine differentiation.
AB  - Our previous microarray-based studies identified secretagogin to be highly
      expressed in normal colon mucosa compared to basal expression in colon
      adenocarcinomas. The aim of this study was to analyze the differential expression
      of secretagogin in normal mucosa, adenocarcinomas, and neuroendocrine tumors.
      Western blotting, immunohistochemistry, immunofluorescence microscopy and ELISA
      were applied. Western blot analysis detected a 32-kDa secretagogin band in
      samples from normal mucosa. Immunohistochemical analyses on tissue specimens
      showed that secretagogin is exclusively expressed in neuroendocrine cells and
      nerve cells in normal mucosa of the digestive tract. Tissues adjacent to benign
      hyperplasic polyps and adenomas showed a decreased number of secretagogin
      expressing neuroendocrine cells. Secretagogin co-localized with neuroendocrine
      markers (chromogranin A, neuron-specific enolase, synaptophysin) in
      neuroendocrine cells in crypts of normal mucosa, and in tumor cells of
      carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of
      19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as
      well as in neuroendocrine tumors from the lung, pancreas and adrenal gland.
      Secretagogin was detected in plasma from carcinoid patients with distant
      metastasis. Combined immunohistochemical analysis of secretagogin and FK506
      binding protein 65, a protein de novo synthesized in adenocarcinomas,
      distinguished well-differentiated carcinoids, adenocarcinoids and
      undifferentiated carcinomas. We conclude that secretagogin is a novel marker for
      neuroendocrine differentiation.

PMID- 16449822
TI  - Evaluation of serotypes of Streptococcus pneumoniae isolated from otitis media
      patients by multiplex polymerase chain reaction.
AB  - The increasing difficulty in the management of pneumococcal acute otitis media in
      parallel with increases in antimicrobial-resistant strains has led to much
      interest in pneumococcal capsular types for the adoption of effective prevention
      by vaccines. This study shows that multiplex polymerase chain reaction is a
      valuable and expeditious method for the capsular typing of pneumococci. The
      multiplex polymerase chain reaction method accurately detects the majority of
      serotypes and serogroups frequently isolated from pediatric patients with acute
      otitis media, allowing the characterization of the colonization patterns for
      further implications of pneumococcal vaccines.

PMID- 16449823
TI  - Cymetra injections to treat leakage around a tracheoesophageal puncture.
AB  - Tracheoesophageal puncture (TEP) is a commonly used method of voice restoration
      following total laryngectomy, but leakage around the prosthesis is prevalent.
      Several treatments for leakage have been proposed in the literature, but with
      varying success. This paper examines the efficacy of Cymetra to help shrink the
      TEP site and stop leakage. Six patients with leaking TEP sites refractory to
      downsizing and/or cautery were selected for the study. Injection sites were
      determined based on the primary sites of leakage. Cymetra was rehydrated with 1.0
      % lidocaine saline solution and injected via a 23-gauge needle a few millimeters
      deep to the mucosa, approximately 2 mm from the edge. The patients were followed
      for up to 13 months. Following 1 trial of Cymetra injection, 4 patients achieved
      successful results. Only 1 patient has not yet achieved full resolution of
      leakage. Cymetra may provide a safer and more effective option for resolution of
      leakage than other methods currently employed.

PMID- 16449824
TI  - The power of pharmacological sciences: the example of proton pump inhibitors.
AB  - Critics have questioned the foundational principles of pharmacological sciences
      and modern drug therapy; they also claim that drug therapy is often too expensive
      or of uncertain value. Contemporaneously, alternative medicine has bloomed. Yet
      the US government began to pay for drug therapy under Medicare in 2006, an
      explicit recognition of the value of modern drug therapy. To clarify this
      confusion, we review the philosophical and scientific foundations of
      pharmacology, drug discovery and development, the attendant strategies and
      successful results. We also review and answer the major attacks on the
      philosophical and scientific foundations of modern pharmacology and drug therapy.
      Finally, we define the characteristics of an ideal drug. As an example of the
      principles and strategies of modern pharmacological sciences and their successful
      application, we focus on the discovery and development of proton pump inhibitors
      (PPIs) of stomach acid production. This class of drugs approaches the ideal and
      exemplifies successful application of modern pharmacological principles to drug
      discovery and development. Moreover, the use of PPIs as a pharmacological tool
      allowed the resolution of important scientific questions, e.g., the role of
      stomach acid in peptic diseases of the stomach, duodenum and esophagus.

PMID- 16449825
TI  - Developing paediatric cardiology in the developing countries.

PMID- 16449826
TI  - Treating fractures rationally.

PMID- 16449827
TI  - The future for new doctors.

PMID- 16449828
TI  - Cardiovascular disease in women.

PMID- 16449829
TI  - Clinical study of sentinel lymph node biopsy in early uterine cervical carcinoma.
AB  - BACKGROUND: Radical hysterectomy and complete pelvic lymphadenectomy is the
      standard treatment for early cervical carcinoma. But the rate of pelvic and
      paraaortic nodal metastasis is found to be low, pointing that most of the
      patients possibly undergo unnecessary nodal dissection. AIM: To study the value
      of sentinel lymph nodes (SLNs) in prediction of the pelvic lymph node status and
      to determine the significance of SLN detection in pelvic lymph node dissection in
      patients with early stage cervical carcinoma. SETTINGS AND DESIGN: Retrospective
      study. METHODS: From August 2002 to August 2004, 20 patients with early stage
      cervical carcinoma, planned to undergo radical hysterectomy and extensive pelvic
      lymph node dissection received an intracervical injection of a blue dye to
      identify and perform resection of SLN. The SLNs were pathologically compared with
      non-SLNs with frozen section, paraffin section, and anti-cytokeratin
      immunohistochemical staining. RESULTS: Out of 20 patients, SLNs were detected in
      15 patients. A total of 46 SLNs were identified and the mean was 3 per patient.
      The detection rate of SLN was 75%. Sensitivity, specificity and accuracy of the
      SLN biopsy were 75%, 100% and 95%, respectively. CONCLUSION: SLN detection can
      predict the pelvic lymph node status in early stage cervical carcinoma, but the
      feasibility and safety of this technique to substitute conventional surgical
      modality should be evaluated by large series of prospective studies.

PMID- 16449830
TI  - Correlation between serum-ascites albumin concentration gradient and endoscopic
      parameters of portal hypertension.
AB  - OBJECTIVE: We sought to determine the correlation between the level of serum
      ascites albumin concentration gradient (SAAG) and the complications of portal
      hypertension (PHTN), manifested by the presence and grade of esophageal varices
      (EV). MATERIAL AND METHODS: Our study included 32 patients with ascites,
      demonstrated by ultrasonography, who had measurement of the SAAG. All had upper
      gastrointestinal endoscopy with assessment of the presence and size of EV. High
      SAAG was considered to be present when SAAG was >=1.1 g/dl and Low SAAG when it
      measured < 1.1 g/dl. RESULTS: We found that 25 of 32 (78.13%) patients had High
      SAAG and 7 of 32 (21.87%) had Low SAAG. Esophageal varices were present in 18 of
      25 (72%) patients with High SAAG and in none of 7 (0%) patients with Low SAAG (p
      =<0.001). Among patients with High SAAG, EV were present in four of 8 patients
      (50%) with SAAG values of 1.10-1.49g/dl; in four of seven patients (57.1%) with
      SAAG values of 1.50-1.99g/dl; and in ten of ten (100%) with SAAG values of
      >=2.0g/dl (p = 0.037). The size of the esophageal varices had no association with
      the level of SAAG in patients with High SAAG (p = 0.426). CONCLUSIONS: In
      patients with ascites the presence of esophageal varices is associated only with
      patients with High SAAG. The presence of EV in patients with ascites and High
      SAAG is directly related to the degree of SAAG. The size of the EV in patients
      with ascites and High SAAG is not associated with the degree of SAAG.

PMID- 16449831
TI  - Lipid peroxidation and antioxidant enzyme status in oral carcinoma patients.
AB  - OBJECTIVE: To measure the lipid peroxidation and endogenous antioxidant enzyme
      status in oral carcinoma and the protective role of exogenous antioxidants.
      MATERIAL AND METHODS: 20 new cases of histologically proven oral squamous cell
      carcinoma, 20 of leukoplakia and 20 age and sex matched healthy conrols were
      included. Intra oral pH of patients and controlled were measured by quantitative
      litmus paper test and serum was analysed for malonialdehyde (MDA), super oxide
      bismutase (SOD), catalase and glutathione peroxidase (GP). Patients with
      leukoplakia were treated with exogenous antioxidants for 3 months and the same
      were reassessed. RESULTS: Oral pH of oral cancer patients was neutral (PH-7) but
      that of leukoplakia and controls were mildly acidic (6.64 and 6.58 respectively).
      Serum malonialdehyde levels were highest in oral cancer group. With antioxidant
      enzymes super oxide bismutase, catalase and glutathione peroxidase different
      pattern was noticed. Antioxidant enzymes remained almost the same (P > 0.005
      each) in patients with leukoplakia after 3 months of vitamin A,C and E. but there
      was marginal increase in catalase level (P<0.05). CONCLUSION: This study shows
      the positive benefit of vitamin (A,C,E) and nutrition supplementation on the
      antioxidant enzyme defense system hence prevention of oral carcinogenesis in
      patients with leukoplakia.

PMID- 16449832
TI  - Pattern of intraocular pressure changes following manual small incision cataract
      surgery.
AB  - OBJECTIVES: To find out the pattern of changes in intraocular pressure after
      manual small incision cataract surgery. METHODS: Consecutive patients (291 eyes
      of 291 patients) undergoing manual small incision cataract surgery were
      prospectively evaluated for change in IOP. Patients were further divided into two
      groups based on whether or not sutures were used to close the scleral tunnel. IOP
      was serially measured at day 1, 1st, 2nd, 4th, 6th, 8th and 12th week. RESULTS:
      The mean post operative IOP in eyes where sutures were not applied (12.59+/- 3.02
      mmHg, 12.59+/-2.34mmHg, 12.54+/-2.19mmHg and 12.40+/-2.99 mm Hg at day1, 2week
      and 4weeks respectively) was lower than that where sutures were used to close the
      wound (15.57+/- 3.86mmHg, 14.05+/-2.52mmHg, 14.43+/-3.39mmHg at day1, 2weeks and
      4 weeks respectively). There was a drop of IOP from the preoperative IOP in both
      suture (1.15+/-3.29mm Hg) and non suture (3.29+/-3.07mm Hg) group at 3 months of
      follow up. CONCLUSION: There is a small drop of IOP following sutureless MSICS
      during long term follow up. Eyes where sutures are applied are more likely to
      have higher IOP than those without sutures at the initial post operative period.

PMID- 16449833
TI  - Anthropometric studies on students of the Nepal Medical College: elbow breadth.
AB  - BACKGROUND: Body mass index is a valuable tool to assess the nutritional status
      of an individual. It can be used to identify subjects who are underweight and
      obese. The present study was conducted with a view to identify the prevalence of
      underweight and obesity among Nepalese medical students. The study also detects
      the body frame size of these medical students by elbow breadth measurements. AIM
      OF STUDY: To measure Body mass index and body frame size based on elbow breadth
      measurements. MATERIALS AND METHODS: A total of 191 (males, 106) students
      participated in the study. The ratio of male to female was 1.24:1. The elbow
      breadth was measured by a vernier caliper (Tajima, Japan) to the nearest 0.1 mm.
      The body mass index (kg/m2) (BMI) was calculated using the height and weight
      measurements taken previously. Body frame size was obtained using a table based
      on elbow width. Data were analyzed using Microsoft excel for Windows 98. RESULTS:
      The study reveals that the prevalence of underweight and overweight in males of
      Nepal Medical college Vth batch were 30% and 1% and of IVth batch were 23.2% and
      12.15% respectively. Of the females 38.6% and 2.2% of the IVth batch and 36.6%
      and 4.9% of the Vth batch were underweight and overweight respectively. The body
      frame size results indicted that 70% of the males and 61% of the females had
      small body frame. The study revealed a significant degree of under nutrition in
      male (26.4%) and female (20%) of Nepalese medical students. CONCLUSION: The
      present study observed that majority of the medical students of the Nepal Medical
      College were of small body frame size.

PMID- 16449834
TI  - Our experience with epidural steroid injections in management of low backpain and
      sciatica.
AB  - BACKGROUND: Low back pain and sciatica is a common clinical condition. It is a
      most common orthopaedic complaint in the Kaski region of Nepal. The reason for
      its increased incidence may be hilly terrain, difficult working and living
      environment of the region. The initial treatment of Low back pain is
      conservative. Epidural steroid injection is being slowly established as are
      liable mode of conservative management in many orthopaedic centres of the world.
      This is a preliminary report of on-going study of the use of epidural steroid in
      the management of low back pain cases coming to the orthopaedic department of
      Manipal Teaching Hospital. METHODS: Prospective clinical trial was carried out on
      the patients reporting with low back pain and sciatica not responding to other
      modes of conservative treatment. Pre and post injection evaluation was done
      clinically. The level of pain, improvement in physical signs and ability to do
      activities of daily living were noted. RESULTS: Fifty two patients were observed
      for the average duration of 2.87 months. Average duration of symptoms was for 10
      months. After first epidural steroid injection 83% of patients reported relief on
      day one. In some cases the onset of analgesia was delayed. Four patients reported
      no relief after first injection. Fifteen patients were given two injections and
      four received three injections. The average duration between two injections was
      three weeks. Average duration of pain relief was 20 days. At the end of 3 months,
      good results were seen in 39%, fair in 33% and bad results in 27%. Overall 59% of
      patients were able to do activities of daily living. Three patients
      (5.76%)required operation for disc prolapse. Postoperatively two patients
      reported back with back pain. Most common complaint of patients after injection
      was pain at the injection site. No major complications were encountered.
      CONCLUSION: Epidural Steroid Injection is a safe and effective mode of treatment
      of Low Back Pain. It provides painfree period to enable the patient for
      physiotherapy which helps in early recovery.

PMID- 16449836
TI  - Detection and co-ordinated care management of chronic kidney disease at Kathmandu
      Medical College Teaching Hospital.
AB  - OBJECTIVE: The objective of our study was to analyze the detection parameters,
      categorization and co-ordinated management of Chronic Kidney Disease (CKD). The
      presenting clinical features, common lab investigations, applied treatment
      protocols and noticed complications were recorded. METHODOLOGY: A total of 40
      patients of various stages of CKD on the basis of National Kidney Foundation
      (NKF), Kidney Disease Outcome Quality Initiative (K/DOQI) guideline were included
      in the study. RESULT: Out of them 24(60%) were males and 16(40%) were females.
      Constitutional symptoms like anorexia, nausea and generalized weakness were
      common presenting complaints present in 37(92.5%) patients and were associated
      with features of anaemia, metabolic acidosis and fluid overload in stage 5 CKD
      patients. The average age of presentation was 51.3 years. Among 40 patients
      21(52.5%) were managed conservatively, 17((42.5%) were advised for Renal
      Replacement Therapy (RRT) through dialysis.2 (5%) patient expired during the
      treatment. The average duration of hospital stay was 5.6 days. Diabetes Mellitus
      was the most common cause 18 (45%), followed by Hypertension 14 (35%) and Chronic
      Glomerulonephritis (CGN) 5 (12.5%) leading to CKD. The patients were advised for
      regular follow up at Nephrology clinic.

PMID- 16449835
TI  - Prevalence of Helicobacter pylori in Dhulikhel Hospital, Kathmandu University
      Teaching Hospital: a retrospective histopathologic study.
AB  - OBJECTIVE: The main objective of this study was to determine prevalence of
      Helicobacter pylori infection in Dhulikhel Hospital, Kathmandu University
      Teaching Hospital. METHODOLOGY: Endoscopic antral biopsies from January 1, 2004
      to August 31, 2005 were studied retrospectively. Hematoxylin and eosin and Giemsa
      stained histological sections were examined. RESULTS: Out of 224 patients (Male
      125 and female 99) who underwent endoscopic biopsy and included in the study, a
      total of 76 (33.9%) patients (Male 50 and female 26) were infected by H. pylori.
      The mean age of the H. pylori infected patients was 40.2 years (SD 16.0). The
      infection by H. pylori was significantly higher in males than females (p<0.05)
      with male to female ratio of 1.9:1. The most common (31.3%) histopathologic
      finding was chronic superficial gastritis followed by normal histology (30.8%). A
      total of 10 cases (4.5%) of adenocarcinoma and 16 cases (7.1%) of intestinal
      metaplasia were detected and neither of them showed presence of H. pylori. Two
      cases (0.9%) were diagnosed as suspected malignancy and both were negative for H.
      pylori infection. Among gastritis, H. pylori was most frequently observed in
      chronic active gastritis (86.1%). Two of 69 cases (2.9%) of normal gastric mucosa
      showed H. pylori.

PMID- 16449837
TI  - Ectopic pregnancy - two years review from BPKIHS, Nepal.
AB  - Ectopic pregnancy remains an important cause of morbidity and mortality in early
      pregnancy. The incidence has increased worldwide with an increase in pelvic
      infections and improvements in the diagnostic techniques. The objective of this
      study was to analyse the various aspects of ectopic pregnancy with a view to
      suggest interventions which would decrease the incidence. MATERIAL AND METHODS:
      The study was carried out in the department of Obstetrics and Gynaecology, B.P
      Koirala Institute of Health Sciences, Dharan (Nepal). Data were analysed
      retrospectively using the case sheets and operative notes from the past two years
      (April 02-April 04). The gynaecological admissions and records of the total
      births within the period of study were also used in the analysis. RESULT: The
      incidence of ectopic pregnancy during this study period was 0.93 of total births
      and 2.92% of the total gynaecological admissions. The peak age of incidence was
      in the range of 26-30 years. Majority of patients were in the lower socioeconomic
      group. Pelvic inflammatory disease and induced abortions were the major risk
      factors. Their contribution was 61.3% and 38.6% respectively. 70.6% of patients
      did not use any contraception. 16% used depo provera. Abdominal pain (69.3%),
      vaginal bleeding (45.3%) and syncopal attacks (21.3%) were the most frequent
      presenting complaints. 58.6% had amenorrhea of 6-10 weeks. Only 1.3% presented
      with amenorrhea of greater than 10 weeks. Ampulla (62.6%) followed by isthmus
      (21.3) were the commonest sites of ectopic implantation. Ovarian and abdominal
      pregnancies contributed to only 1.3% each. There was no significant difference
      between the side of the tube involved.82.6% had come with ruptured ectopic but
      only 12% were in shock. Majority of patients underwent salpingectomy (69.3%)
      followed by salpingo-oophorectomy (17.3%). Only 2.6% received methotrexate. 70.6%
      required blood transfusion. CONCLUSION: Majority of patients attending BPKIHS for
      ectopic pregnancy were between 26-30 years and had history of PID & induced
      abortions. Surgery (salpingectomy/salpingo-oophorectomy) was the main stay of
      treatment.

PMID- 16449838
TI  - Antimicrobial utilization pattern in out patient services of ENT department of
      tertiary care hospital of Eastern Nepal.
AB  - OBJECTIVE: The objective of this study was to monitor the antimicrobial
      utilization in ENT out patient services in a tertiary care hospital of Nepal.
      MATERIALS & METHODS: A total of 191 prescriptions were randomly audited at
      varying time interval from the department of ENT in the year 2003. The data was
      collected in customized Performa in the form of antibacterial audit
      questionnaires. It also contained Patient particulars, diagnosis, investigations,
      drug details and information from the prescriber regarding the indication for
      prescribing antimicrobial agent, suspecting organism underlying infection,
      duration of therapy and details of any concomitant medications. RESULTS: The
      incidence of use of antimicrobial agents (AMA) in 191 prescriptions was analyzed
      from the enrolled prescriptions, a total of 218 antimicrobials i.e.1.4
      antimicrobial agent per patient were prescribed. . The AMAs were indicated
      therapeutically in 73.29% of patients & 19.37% patients for prophylaxis. The AMAs
      were advised for more than 72 hours for prophylaxis in 86.48%. In the concomitant
      medications antihistaminic were prescribed in 32.62% and NSAIDS in 21.98% cases.
      Most of patients reported with upper respiratory tract infections (URTI-32.56%),
      Chronic Suppurative otitis Media (CSOM-18.3%), sinusitis (6.28%), tonsillitis
      (5.75%),. Pharyngitis (3.66%), Acute Suppurative Otitis Media (ASOM-2.61%) and
      others. The diagnosis was established clinically in 42.40% and confirmative in
      35.60%. In 21.46% the diagnosis was not disclosed. Out of 191 patients, culture
      sensitivity tests were performed for only 31 patients and 13 patients depicted a
      positive culture sensitivity tests. The common microbes isolated from the culture
      were staphylococcus aureus (69.2%). Streptococcus (7.7%), Enterobacteriacae
      (7.7%), Pseudomonas auroginosa (7.7%) & psendomanas mirabilis (7.7%). Clinically
      suspected organism were mentioned in only 32 prescriptions and most prescriber
      presumed the infections due to staphylococci & pseudomonas (43.75%), streptococci
      (21.8%),Gram negative organisms (12.5%) and H influenza (9.3%). The use of a
      single drug was abundant (89.52%), two drugs (9.94%), and three drugs (0.52%
      )prescriptions. Ciprofloxacin (23.85%) was preferred, followed by amoxycillin
      (20.06%), combination of ampicillin + cloxacillin( 9.17%), doxycyclin (5.96%).
      Erythromycin (4.58%) and cotimoxazole (4.58%). Expensive drugs i.e azithromycin
      (2.75%), roxithromycin (1.37%) and cephalosporins (3.21%) were also prescribed.
      The causative microbes were sensitive to amoxycillin (53.84%), cloxacillin
      (53.84%) ciprofloxacin (46.15%), gentamicin (46.15%), and cephalosporin (46.15%).
      But resistant to erythromycin, tetracycline, cotrimoxazole and norfloxacin)
      CONCLUSIONS: Majority of patients were prescribed drugs irrationally with
      misleading indications without confirming the bacteriological culture and
      sensitivity.

PMID- 16449839
TI  - Study of clinical profile and antibiotic sensitivity pattern in culture positive
      typhoid fever cases.
AB  - OBJECTIVES: The present study was designed to analyze the clinical profile and
      antibiotic sensitivity pattern in the cases of culture positive typhoid fever.
      METHOD: The study was conducted over a period of 1 year. Total of 46 culture
      positive cases of Typhoid fever were included in the study. The sensitivity
      pattern of isolates from blood culture was recorded. The modes of presentation,
      clinical course, lab investigation reports were also recorded. RESULTS: Out of 46
      cases, 33 (71.7%) were males and 13 (28.3%) were females. Average age of
      presentation was 26.17 years. Fever was present in all patients. Resistance of S
      .typhi to amoxycillin, chloramphenicol and co-trimoxazole were significantly
      high. Ciprofloxacin showed resistance in 2 (4.3%) cases. Sensitivity to
      ceftriaxone was 100% in our study. CONCLUSION: Typhoid fever is one of the most
      common health problem in Nepal. Various drugs are being used in the treatment of
      typhoid fever, in the mean time resistance to many of them are emerging. An
      appropriate antibiotic has to be initiated only after culture sensitivity in
      typhoid fever.

PMID- 16449840
TI  - Effectiveness of structured teaching program in improving knowledge and attitude
      of school going adolescents on reproductive health.
AB  - INTRODUCTION: Development of knowledge and attitude takes place during the
      adolescent period, which can have lifelong effects on the individual, family and
      society. Proper education in this age group is important for prevention of
      untoward social and health related problems. OBJECTIVE: To find out the
      effectiveness of structured teaching program in improving knowledge and attitude
      of school going adolescents on reproductive health. MATERIALS AND METHODS: An
      experimental study with pretest - posttest control group design was carried out
      in four selected schools with similar settings in Dharan town of Nepal. All the
      subjects were divided into two groups: experimental and control, each comprising
      of two subgroups of 50 boys and 50 girls. Structured teaching program consisting
      of information on human reproductive system was used as a tool of investigation
      for the experimental group, whereas conventional teaching method was used for the
      control group. RESULTS: A total of 200 Adolescent school students were included
      in this study. The mean (+/-SD) pretest score of the experimental group on
      knowledge of reproductive health was 39.83 (+/- 16.89) and of the control group
      was 39.47(+/- 0.08). The same of experimental group after administration of the
      structured teaching program (84.60+/-10.60) and of the control group with
      conventional teaching method (43.93+/-10.08) was statistically significant
      (p<0.001). Similarly, the post-test scores of knowledge of the groups on
      responsible sexual behaviour and their attitude towards reproductive health were
      better in the experimental group than in the control group (p<0.001). CONCLUSION:
      The knowledge of adolescent school students on reproductive health is inadequate.
      The use of structured teaching program is effective in improving knowledge and
      attitude of the adolescents on reproductive health.

PMID- 16449841
TI  - Benign and malignant breast disease presenting to Bhaktapur Cancer Hospital.
AB  - OBJECTIVE: In the absence of formal breast screening services in Nepal, patients
      must self present upon developing symptoms relating to the breast. Clinical
      examination and diagnostic tests are then used to differentiate benign and
      malignant conditions. Referral / presentation patterns are not well studied and
      this paper aims to investigate this. METHOD: Here we present the clinico
      pathological diagnoses of patients presenting to Bhaktapur Cancer Hospital with
      breast related complaints within a six month period, and report upon their
      subsequent management. RESULTS: 727 patients presented with breast related
      complaints, of whom 34 were diagnosed with breast cancer. These tended to present
      at late stage and their subsequent management is discussed. CONCLUSION: As the
      incidence of breast cancer in Nepal is likely to be under-reported and more than
      likely rising, patient awareness campaigns are underway in order to facilitate
      the earlier diagnosis of malignant disease and thus beneficially influence
      treatment outcomes. To this end the need for the development of dedicated breast
      services is highlighted.

PMID- 16449842
TI  - A study of poisoning cases in emergency Kathmandu Medical College Teaching
      Hospital.
AB  - OBJECTIVE: To determine the pattern and severity of poisoning cases in emergency
      Kathmandu Medical College Teaching Hospital. DESIGN: Retrospective observational
      study. MATERIALS AND METHODS: All the poisoning cases due to various agents who
      attended Emergency from 1st of April 2002 to 30th of March 2003 were evaluated
      retrospectively. RESULTS: A total of 67 poisoning cases attended emergency
      Kathmandu Medical College Teaching Hospital over a period of one year. The
      overall female to male ratio was 1.09:1. Most poisoning occurred in the age group
      21-30 for adults (38.8%) and 2-5 yrs for the children. Organophosphorous was the
      most common poisoning for the adults where as kerosene was common in children.
      Oral route was the most common route of administration which accounted 86.57%.
      Students (35.8%) and housewife (23.3%) were commonly involved in self poisoning.
      Intentional poisoning comprised 58.2% of all poisonings. CONCLUSION: Majority of
      the intentional poisoning occurred in the female housewife & students of younger
      age group but accidental poisoning was found common in children under five years
      mostly with kerosene ingestion.

PMID- 16449843
TI  - Dose-dependent effect of copper chloride on male reproductive function in
      immature rats.
AB  - BACKGROUND: Copper is essential as a trace element for metabolic processes.
      Exposure to copper in industries develops toxicity among the workers. Previous
      findings on adverse effects of copper on male reproductive function in adult
      albino rats led to investigate the effects of this metal on reproductive function
      of maturing male rats in the present experiment. METHODOLOGY: To study these
      effects, immature (30 to 35 days old) Wistar strain albino rats weighing about 50
      60 g were treated intraperitoneally with copper chloride at doses of 1000, 2000
      and 3000 microg/kg body weight/day for 26 days. RESULT: Significant fall in
      accessory sex organ weight and inhibition of testicular 17beta-hydroxysteroid
      dehydrogenase activity along with degeneration of testicular growing
      spermatogenic cells and reduction in serum testosterone, FSH and LH level were
      observed at the doses of 2000 and 3000microg/kg/day. On the other hand, at the
      dose of 1000 microg/kg/day significant increase in testicular steroidogenic
      enzyme activity and stimulation of testicular spermatogenesis along with rise in
      serum testosterone and LH level were observed, though no significant change was
      observed in serum FSH level. This suggests that copper has got a dose-dependent
      effect on testicular steroidogenesis and spermatogenesis and serum testosterone
      and LH level in maturing male rats.

PMID- 16449844
TI  - Superficial sural artery island flap for management of exposed Achilles' tendon -
      surgical techniques and clinical results.
AB  - OBJECTIVE: Superficial Sural artery island flap is a "island flap" based on
      vascular axis of the sural nerve which gets reverse blood flow through
      communication with the perforating branch of the peroneal artery situated in the
      region of lateral malleolar gutter. Achilles Tendon can be exposed due to trauma,
      post-operative wound dehiscence, infection etc. This exposed tendon requires
      immediate coverage to avoid complications. This versatile flap provides an
      excellent coverage for the exposed tendoachilles and has definitive advantages
      such as being easy to raise, having a wide range of arc of rotation, not
      compromising major arteries of the leg, requiring minimal expertise and infra
      structural facilities, and having less morbidity to donor site and being a single
      staged surgery. METHODOLOGY: Thirty patients with exposed Achilles' tendon were
      treated with Superficial Sural Island Flap with excellent outcome. The present
      study was carried out in the Department of Plastic and Reconstructive Surgery,
      National Institute of Traumatology and Orthopaedics Rehabilitation (NITOR), Sher
      e-Banglanagar, Dhaka, Bangladesh between January 2001 to December 2004.

PMID- 16449846
TI  - Anatomical variation of maxillary sinus mimicking a periapical cyst: a case
      report.
AB  - Maxillary sinus can pose diagnostic dilemma radiographically because of its
      anatomical variation which can mimic a periapical pathosis. This case report
      deals with one such diagnostic problem, where a maxillary sinus was interpreted
      in an intraoral periapical radiograph as a periapical cyst. With the advances in
      imaging techniques, the use of an Ultrasound imaging together with application of
      Colour Power Doppler helped in revealing the contents of the radiolucent area and
      come up with an accurate diagnosis. Thus a thorough knowledge about the normal
      anatomy and its variations and proper diagnostic aids are essential in the
      diagnosis of periapical pathology.

PMID- 16449845
TI  - Effectiveness of nicotinic acid and bezafibrate alone and in combination for
      reducing serum triglyceride level.
AB  - OBJECTIVE: To study the effectiveness of nicotinic acid and Bezafibrate alone and
      in combination for reducing triglyceride level. DESIGN: It was a randomised,
      prospective, longitudinal study. SETTING: Patients attending a private clinic,
      and medical department of Kathmandu Medical College, Sinamangal. METHODS: This
      study included 83 consecutive patients, 19 females and 64 males with
      hypertriglyceridaemia (defined as serum triglyceride >200mg/dl) attending the
      department of medicine, Kathmandu Medical College, Sinamangal and private clinic.
      MAIN OUTCOME MEASURES: Statistically significant reduction of serum triglyceride
      level. RESULT: 51 out of 83 patients completed the study in which Nicotinic acid
      alone reduced the serum trygleceride level from 320.62 +/- 104.23 to 182.55 +/-
      46.21, which is a reduction of 138.07 +/- 85.69 (P. value = 001). Bezafibrate
      when given alone also reduced triglyceride level significantly from 345.25 +/-
      181.03 to 203.30+/-93.59 which is a reduction of 141.95 +/- 121.130 (P value=
      .001). When a combination of both drugs was given the reduction of 472.73+/
      247.53 (P value =.002) was achieved. CONCLUSIONS: Nicotinic acid is a very
      effective drug in reducing serum triglyceride level and its effectiveness is
      similar to Bezafibrate. There is no added benefit of giving a combination of
      nicotinic acid and Bezafibrate in reducing serum triglyceride level.

PMID- 16449847
TI  - B-Lynch brace suture simple surgical technique for managing post-partum
      haemorrhage - report of three cases.
AB  - Post-partum haemorrhage is a major contributor to maternal morbidity and
      mortality. Numerous medical and surgical therapies have been used but none has
      been uniformly successful. Three cases which were managed successfully with brace
      suture following failure of medical management for post-partum haemorrhage are
      being presented. The ease and usefulness of this procedure as a life saving
      measure, its relative safety and its capacity for preserving the uterus and thus
      fertility is high lighted.

PMID- 16449848
TI  - Intermediate syndrome in organophosphorous poisoning--a case report.
AB  - A case of organophosphorous poisoning in a 29 year old male who developed
      intermediate syndrome manifested by features of respiratory depression as
      evidenced by marked weakness of the respiratory muscles, tachypnoea, and drop in
      oxygen saturation despite reversal of nicotinic and muscarinic effects of
      organophosphorous poisoning. The case highlights its early recognition and prompt
      institution of mechanical ventilation with continuation of anticholinergic drugs.
      The mechanical ventilation had to be continued for 9 days with successful
      outcome.

PMID- 16449849
TI  - Pedunculated angiomyxoma of the vulva - a rare clinical entity.
AB  - BACKGROUND: Aggressive angiomyxoma is an uncommon mesenchymal tumor that
      preferentially involves the pelvic and perineal regions of females. Since its
      initial description in 1983, approximately 65 cases have been reported in the
      English literature. CASE: A 33-year-old parous woman with a slow growing
      pedunculated soft tissue tumour of the vulva which later underwent surface
      ulceration. Pathological findings in the case were suggestive of an aggressive
      angiomyxoma, a distinctive soft tissue non-malignant tumour, which could, at
      times be locally aggressive.

PMID- 16449850
TI  - HIV/AIDS wasting syndrome in Manipur - a case report.
AB  - A-30-years old married man with HIV/AIDS wasting syndrome is being reported. The
      patient had history of injecting heroin with rampant sharing with his drug
      partners, weight loss, night sweats, productive cough, severe muscle wasting,
      chronic diarrhoea >30 days and fever > 30 days. This syndrome indicates the long
      standing complication of HIV infection. Blood, sputum, CSF, faeces and urine
      routine and culture examination findings to rule out opportunistic infections
      were repeatedly negative. No malignant cells were found. HIV testing was
      positive. The CD 4 positive T-lymphocyte count was measured before and after six
      months of treatment. In the present case report, evaluation of the symptoms
      yielded no specific pathogen and had no evidence of opportunistic infections. He
      is being placed under observation with highly active antiretroviral therapy
      (HAART) along with nutritional support. He is improving clinically and
      immunologically by raising in the patient's CD4 count. Early antiretroviral
      therapy along with meticulous nutritional support is ideal to improve the quality
      of life of AIDS patients.

PMID- 16449851
TI  - Pharmacogenomics - therapeutic and ethical issues.
AB  - Pharmacogenomics deals with the genetic basis underlying variable drug response
      in individual patients. It encompasses sum of all genes. Numerous genes may play
      a role in drug response and toxicity. The newly emerging genomic technologies
      enable the search for relevant genes and their variants to include the entire
      genome and help in the search for candidate genes. Moreover pharmacogenomic
      analysis can identify the disease susceptibility genes representing potential new
      drug targets. The current concept of drug therapy is to apply treatment for a
      large population group whereas application of pharmacogenomic will help
      individual application of drug therapy or on smaller patient sub population but
      whether this individualized medicine will lead to improved and economically
      feasible therapy is yet to be seen. This is again complicated by various ethical
      and legal issues. In this article some of the issues are highlighted.

PMID- 16449852
TI  - Recent advances in the management of epilepsy: a review.
AB  - Epilepsy is a complex disorder affecting brain function having a variety of
      contributing factors. The genetic predisposition plays a key role in the genesis
      of epilepsy. The already existing antiepileptic drugs (AEDs) provide effective
      control of majority of patents with different types of seizures. In some
      refractory cases and in those patients who can not tolerate the conventional
      AEDs, there is an urgent need to provide relief by controlling the seizures
      adequately. Various newer approaches in the rational management of seizures have
      been evolved during the recent years, based on different mechanisms of action and
      side effects profile. A brief account of these newer treatment modalities have
      been incorporated in this review in order to enlighten the readers about the
      possible beneficial effect of this regimen vis a vis the limitations of such use.

PMID- 16449853
TI  - Ocular side effects of antitubercular drugs - a focus on prevention, early
      detection and management.
AB  - Given the increasing prevalence of tuberculosis, antitubercular drugs frequently
      used are also associated with ocular toxicity. Ethambutol is the most commonly
      implicated drug. It is generally well tolerated, but known to cause optic
      neuritis, more specifically retro bulbar neuritis causing blurred vision,
      decreased visual acuity, central scotomas, and loss of red-green color vision.
      The exact mechanism of toxicity is not understood. Though optic neuritis due to
      ethmabutol is generally considered to be reversible upon prompt discontinuation
      of the drug, there are reports of reversible toxicity, particularly in the
      elderly population. Isoniazid can rarely cause retro bulbar neuritis. Dose
      relationship is usually not seen. Streptomycin is known to cause pseudo
      tumorcerebri. Thiacetazone can produce severe cutaneous reactions including
      Steven Johnson Syndrome affecting the skin and mucosa including conjunctiva.
      Educating the patients for early detection of the ocular manifestations and
      regular follow-ups are very essential.

PMID- 16449854
TI  - Entry knowledge and situational feedback of MBBS students.
AB  - INTRODUCTION: A need has been felt to acquire knowledge of students at Kathmandu
      Medical College (KMC) who have decided to take up a medical career and have
      enrolled at KMC after completing two years of basic sciences. OBJECTIVE: The
      intent was to (i) find out the entering status with regard to general knowledge,
      (ii) get feedback from the students about the facilities provided by the
      management both at basic sciences complex at Duwakot and clinical sciences at
      Sinamangal and (iii) get feedback regarding the teaching learning activities
      provided by various departments in KMC. This attempt at getting their point of
      view was for trying to improve upon the facilities by taking up their suggestions
      and doing away with the weaknesses. Preference was given to hostel students as
      they would be able to comment on living conditions. METHODOLOGY: A total of 150
      students from three consecutive batches from basic and clinical sciences were
      included in the study. Survey questionnaires were distributed and all the forms
      were returned. The obtained data was analyzed using SPSS 11.5 version for
      Windows. RESULTS: It was found that the entry knowledge on general issue was
      better in 6th batch of students (87.08+/-17.41) than 5th batch (82.19+/-17.43)
      and 7th batch (78.93+/-20.60), but not significant (p=0.164>0.05). The students
      in different batches differed in their rating of various facilities provided by
      KMCTH. The most liked departments in terms of teaching learning activities were
      departments of Anatomy and Pathology. DISCUSSION: Entry knowledge of the students
      of three batches was found to differ but not significant, correlating with the
      amount of teaching and learning received at KMC. The facilities provided by KMC
      were perceived as more satisfactory by the students who enrolled at KMC in later
      years. The earlier students had to cope with more difficulties as KMC was trying
      to improve on various facilities it provided to its students. CONCLUSION: Level
      of entry knowledge got better as the students attained more and more years of
      teaching and learning activities. It was also seen that the student's perception
      of the quality of facilities provided by KMC got better overtime.

PMID- 16449855
TI  - Medical camps and their usefulness.

PMID- 16449856
TI  - Public Private Partnership - a case study of the Melaka-Manipal Medical College.

PMID- 16449859
TI  - Statement on cardiopulmonary exercise testing in chronic heart failure due to
      left ventricular dysfunction. Recommendations for performance and interpretation.

PMID- 16449858
TI  - The role of complementary and alternative therapies in cardiac rehabilitation: a
      systematic evaluation.
AB  - BACKGROUND: Presently, complementary and alternative medicine, including both
      therapies and herbal/oral supplements, is used globally. Few studies have
      examined the use of specific therapies, separate from herbal/oral supplements, in
      cardiac rehabilitation. This paper presents a systematic evaluation of current
      research evidence related to use of specific complementary and alternative
      medicine therapies in secondary prevention of cardiovascular disease, with a view
      to making recommendations for cardiac rehabilitation. DESIGN AND METHODS: A
      literature search was conducted using complementary and alternative medicine
      websites, Medline, Allied and Complementary Medicine, CINAHL, Cochrane databases,
      EMBASE, SportDiscus, Clinical Evidence, and Evidence-Based Practice to locate
      research-based scientific evidence related to the use of complementary and
      alternative medicine in cardiac rehabilitation. Search keywords included heart,
      cardiac, cardiovascular, coronary, myocardial and rehabilitation, combined with
      particular therapies. Herbal/oral supplements were not included in this
      evaluation. RESULTS: Some complementary and alternative medicine therapies may be
      useful to patients by themselves or coupled with traditional cardiac
      rehabilitation. Tai chi, as a complement to existing exercise interventions, can
      be utilized for low and intermediate risk patients. transcendental meditation may
      be used as a stress reduction technique. There was insufficient evidence found
      for the use of acupuncture or chelation therapy in cardiac rehabilitation or
      secondary prevention. CONCLUSIONS: Some complementary and alternative medicine
      therapies hold promise for patients in cardiac rehabilitation. Further research
      is essential, however, in all areas of complementary and alternative medicine to
      confirm its usefulness as an adjunct to cardiac rehabilitation.

PMID- 16449860
TI  - Trends in the prevalence, awareness, treatment and control of hypertension: the
      WHO MONICA Project.
AB  - OBJECTIVE: To describe the secular changes in the prevalence, awareness,
      treatment and control of hypertension. DESIGN: Two independent cross-sectional
      population surveys using standardized methods conducted between the early 1980s
      and mid-1990s. SETTING: Twenty-four geographically defined populations of the WHO
      MONICA Project. PARTICIPANTS: Randomly selected men and women aged 35-64 years.
      The total number of participants was 69 907. MAIN OUTCOME MEASURES: Two
      definitions of hypertension were used: 160/95 mmHg or above and 140/90 mmHg or
      above for systolic or diastolic blood pressure. Subjects on antihypertensive drug
      treatment were considered to be hypertensive regardless of their blood pressure.
      Treated subjects whose measured blood pressure level was less than 160/95 or
      140/90 mmHg according to the two definitions, respectively, were considered to be
      adequately treated. RESULTS: The age-adjusted prevalence of hypertension
      decreased in most and increased in only a few populations. For both definitions
      of hypertension, the proportion of hypertensive subjects who were aware of their
      condition increased in three-quarters of the male populations and in two-thirds
      of the female populations. Furthermore, the proportion of hypertensive
      individuals on antihypertensive drug treatment increased in three-quarters of the
      populations. In the final survey, hypertension tended to be better treated and
      controlled in women than in men. Nevertheless, a large proportion of patients
      receiving antihypertensive drug therapy still had inadequately controlled blood
      pressure levels. CONCLUSION: Although awareness and treatment of hypertension
      according to the data obtained during the late 1980s to the mid-1990s increased
      in several populations, the effectiveness of antihypertensive treatment showed
      the continuing need for improvements.

PMID- 16449861
TI  - Coronary risk prediction for those with and without diabetes.
AB  - BACKGROUND: Coronary risk prediction 'engines' are now in common use, and their
      worth is well proven. There remains the question of how to deal with a prior
      diagnosis of diabetes. DESIGN: An individual participant meta-analysis of 33
      cohort studies involving 364 566 subjects. METHODS: Fatal coronary hazard ratios
      for age, smoking, systolic blood pressure and cholesterol, were computed from Cox
      models, comparing those with and without diabetes. Three risk prediction
      equations were compared: a 'stepped model', which included the risk factors and
      diabetes status; an 'interaction model', which included interactions between
      diabetes and the risk factors; and a 'fixed model', which fixed the 10-year rate
      of coronary death amongst those with diabetes to be 7%. These were compared
      through the area under the receiver operating characteristic curve (AUC) and
      Hosmer-Lemeshow statistics. RESULTS: The hazard ratio for age was greater for
      those without diabetes than those with, for men (P=0.005) and women (P=0.02); for
      men only, systolic blood pressure showed a similar differential (P=0.011).
      Nevertheless, AUCs were only 0.001 different for the stepped and interaction
      models for each sex. The AUC for the fixed model was lower and, unlike the other
      two, showed significant lack of fit for both sexes (P<0.001). CONCLUSIONS: There
      is no justification for developing separate risk prediction models for those with
      and without diabetes, nor for assuming that everyone with diabetes should be
      considered as being at a common high level of risk. Diabetes status might,
      instead, be used as a risk variable in an overall population equation.

PMID- 16449862
TI  - Is exercise testing useful to improve the prediction of coronary events in
      asymptomatic subjects?
AB  - OBJECTIVE: The value of exercise testing (ET) in asymptomatic subjects remains
      controversial and is unknown in countries with a low coronary heart disease (CHD)
      incidence. The aim of this study was to investigate the ability of ET to improve
      the prediction of a first coronary event in such a population. METHODS: Using a
      prospective cohort study, 1051 consecutive healthy asymptomatic adults were
      enrolled in a cardiovascular screening program including ET. The pre-test risk of
      CHD was evaluated by the 10-year Framingham risk function. Positive ET was
      defined as a horizontal or downsloping ST-segment depression >/=1.0 mm. The
      primary outcome was total coronary events (CE) occurrence, including cardiac
      deaths, acute myocardial infarction and stable or unstable angina. The mean
      follow-up period was 6 years. RESULTS: Subjects were aged 18-79 years and 36%
      were women. A total of 89 subjects (8.5%) had a positive ET. Positive exercise
      testing was associated with CE occurrence in a univariate analysis only in
      subjects with higher pre-test risk, defined by a 10-year Framingham risk >10.4%
      [hazards ratio (HR)=2.61; 95% confidence interval (CI) (1.07-6.40)]. In this risk
      category, ET was able to provide incremental information over the major risk
      factors in both men and women [risk factor-adjusted HR for positive ET=2.86; 95%
      CI (1.14-7.20)]. This risk excess in subjects with positive ET persisted even
      when a coronary revascularization was performed. Subjects with intermediate pre
      test probability (10-15%) and positive ET had a post-test probability of CE
      largely equivalent to the probability in subjects with known CHD. CONCLUSION:
      Additional information provided by ET in subjects with a pre-test risk at 10
      years >10% should lead to a more efficient use of risk-reducing therapies than it
      would be the case in this risk category with the analysis of traditional risk
      factors only.

PMID- 16449863
TI  - Implications of exercise test modality on modern prognostic markers in patients
      with known or suspected coronary artery disease: treadmill versus bicycle.
AB  - BACKGROUND: Important modern prognostic markers such as heart rate recovery
      (HRR), chronotropic index, delayed systolic blood pressure (SBP) response and
      Duke treadmill score (DTS) have been evaluated by treadmill exercise testing.
      Their value in bicycle exercise testing is unclear. METHODS: Patients (n=211, age
      64+/-10; 75% male) with known or suspected coronary artery disease randomly
      underwent either bicycle (n=105) or treadmill (n=106) exercise
      electrocardiography. They were matched for age, gender, body mass index,
      hypertension, smoking, lipid status, prevalence of diabetes, medication,
      haemoglobin level, extent of coronary artery disease and left ventricular
      ejection fraction. RESULTS: Despite a higher peak heart rate (pHR) patients
      stressed by treadmill had a slower drop in HR during the early phase of recovery
      with a significantly higher rate of abnormal HRR (pHR; HR 1 min into recovery <
      or =12 bpm) with 37% in treadmill versus 19% in bicycle (P=0.004). Abnormally
      delayed SBP response [(SBP 1 min into recovery/SBP 3 min into recovery) >1.0] was
      also more common in treadmill (41%) compared to bicycle (12%, P<0.001). However,
      the rate of chronotropic incompetence [(pHR - rest HR)/(220 - age - rest HR)
      <0.8] was significantly lower in treadmill than in bicycle (60 versus 76%,
      P<0.001). Mean DTS was also significantly higher in treadmill compared to bicycle
      (4.8+/-6.5 versus 3.6+/-5.1, P=0.03) mainly due to the higher workload achieved
      when patients were stressed by treadmill (8.5+/-2.5 versus 6.1+/-1.5 metabolic
      equivalents, P<0.001). CONCLUSIONS: Further adjustment is needed prior to routine
      incorporation of these important measures into interpretation of bicycle exercise
      testing.

PMID- 16449864
TI  - Different forms of physical activity and cardiovascular risk factors among 24-64
      year-old men and women in Finland.
AB  - BACKGROUND: There is convincing evidence that regular physical activity reduces
      risk factors for cardiovascular diseases (CVD) among men. However, only a few
      studies have been conducted among women. Most previous studies have focused on
      the effects of leisure-time physical activity on cardiovascular risk factors,
      without considering the impact of occupational or commuting physical activity.
      DESIGN: Four independent cross-sectional surveys were carried out at 5-year
      intervals within the framework of the FINMONICA studies in 1982, 1987, 1992 and
      1997. METHODS: An independent random sample was drawn from the national
      population register for each survey. The samples were stratified by sex and 10
      year age categories according to the WHO MONICA protocol. The survey consisted of
      a self-administered questionnaire. RESULTS: Not only leisure-time physical
      activity, but also commuting activity was directly associated with high-density
      lipoprotein (HDL)-cholesterol and was inversely related to body mass index (BMI)
      and waist circumference among both men and women. High occupational physical
      activity was related to high HDL-cholesterol levels and high total serum
      cholesterol levels in both sexes and to lower BMI, waist circumference and
      diastolic blood pressure (DBP) in men. High leisure-time physical activity was
      associated with reduced DBP among both men and women, whereas high occupational
      physical activity was related to lower DBP only among men. CONCLUSION: Not only
      leisure-time physical activity but also commuting activity is associated with
      reduced levels of some cardiovascular risk factors. All forms of physical
      activity should be promoted to reduce CVD in the population.

PMID- 16449865
TI  - Predicting cardiac rehabilitation enrollment: the role of automatic physician
      referral.
AB  - BACKGROUND: Despite the established benefits of cardiac rehabilitation, evidence
      suggests referral to, and subsequent enrollment in, cardiac rehabilitation
      following a coronary event remains low (10-25%). The aim of this study was to
      identify predictors of attendance to cardiac rehabilitation intake and subsequent
      enrollment in rehabilitation after coronary artery bypass graft surgery within
      the framework of an automatic referral system. DESIGN AND METHODS: We conducted a
      historic prospective study of patients who underwent coronary artery bypass graft
      surgery between 1 April 1996 and 31 March 2000 and lived within the geographic
      referral area of a multi-disciplinary cardiac rehabilitation center in central
      south Ontario, Canada. Coronary artery bypass graft surgery patients are
      automatically referred to cardiac rehabilitation at the time of hospital
      discharge. Consecutive health records of eligible patients were reviewed for
      medical history, cardiac risk factor profiles, and evidence of cardiac
      rehabilitation intake attendance and enrolment. RESULTS: A total of 3536 patients
      met eligibility criteria. Patients were predominantly male (79.1%), approximately
      64 years of age, living with a spouse or a partner, English-speaking, retired and
      had multiple cardiac risk factors. Of eligible patients, 2121 (60.0%) attended
      the cardiac rehabilitation intake appointment. Of patients who attended cardiac
      rehabilitation intake 1463 (69%) enrolled in at least one cardiac rehabilitation
      service, based on their risk factor profile. Selected cardiac rehabilitation
      services were exercise training (n=1287; 88%), nutrition counseling (n=571;
      39.0%), nursing care (n=546; 37.3%), and psychological intervention (n=223;
      15.2%). CONCLUSIONS: An institutionalized, physician-endorsed system of automatic
      referral to cardiac rehabilitation resulted in higher rates of cardiac
      rehabilitation intake and enrollment following coronary artery bypass graft
      surgery than previously reported and should be adopted for all cardiac
      populations.

PMID- 16449866
TI  - Effects of exercise rehabilitation program on heart rate recovery in patients
      with chronic heart failure.
AB  - BACKGROUND: Heart rate recovery (HRR1) immediately after exercise reflects
      parasympathetic activity, which is markedly attenuated in chronic heart failure
      (CHF) patients. The aim of our study was to examine both continuous and interval
      exercise training effects on HRR1 in these patients. DESIGN: The population study
      consisted of 29 stable CHF patients that participated at a rehabilitation program
      of 36 sessions, three times per week. Of the 29 patients, 24 completed the
      program. Patients were randomly assigned to interval {n=10 [100% peak work rate
      (WRp) for 30 s, alternating with rest for 30 s]} and to continuous training [n=14
      (50%WRp)]. METHODS: All patients performed a symptom-limited cardiopulmonary
      exercise test on a cycle ergometer before and after the completion of the
      program. Measurements included peak oxygen uptake (VO2p), anaerobic threshold
      (AT), WRp, first degree slope of VO2 during the first minute of recovery (VO2/t
      slope), chronotropic response [% chronotropic reserve (CR)=(peak HR - resting
      HR)x100/(220 - age - resting HR)], HRR1 (HR difference from peak exercise to one
      minute after). RESULTS: After the completion of the rehabilitation program there
      was a significant increase of WRp, VO2p, AT and VO2/t-slope (by 30%, P=0.01; 6%,
      P=0.01; 10%, P=0.02; and 27%, P=0.03 respectively for continuous training and by
      21%, P<0.05; 8%, P=0.01; 6%, P=NS; and 48%, P=0.02 respectively for interval
      training). However, only patients exercised under the continuous training regime
      had a significant increase in HRR1 (15.0+/-9.0 to 24.0+/-12 bpm; P=0.02) and CR
      (57+/-19 to 72+/-21%, P=0.02), in contrast with those assigned to interval
      training (HRR1: 21+/-11 to 21+/-8 bpm; P=NS and CR: 57+/-18 to 59+/-21%, P=NS).
      CONCLUSIONS: Both continuous and interval exercise training program improves
      exercise capacity in CHF patients. However, continuous rather than interval
      exercise training improves early HRR1, a marker of parasympathetic activity,
      suggesting a greater contribution to the autonomic nervous system.

PMID- 16449867
TI  - Resistance exercise training attenuates alcohol-induced cardiac oxidative stress.
AB  - BACKGROUND: Myocardial oxidative stress is believed to play an important role in
      the pathogenesis of alcoholic cardiomyopathy. Strenuous physical exercise has
      been shown to increase or decrease myocardial oxidative stress depending on the
      mode and duration of the exercise intervention. Given the possibility of
      individuals to engage in both alcohol consumption and weight-training exercise,
      we have examined the effect of resistance exercise training and chronic alcohol
      consumption on myocardial oxidative stress in rats. METHODS: Forty Sprague-Dawley
      rats were randomly assigned to one of four experimental groups: sedentary,
      sedentary plus alcohol treatment, resistance training, or resistance training
      plus alcohol treatment. Rats in the alcohol groups received a liquid diet
      containing alcohol (35% of kilocalorie intake) for 6 weeks. Non-alcohol groups
      were pair-fed the same liquid diet supplemented with a maltose dextrin caloric
      substitute. Rats in the resistance training groups were trained to rise onto
      their hind limbs while wearing lead-weighted vests 30 times per training session,
      3 days per week during the 6 week experimental period. RESULTS: Alcohol treatment
      in the sedentary animals resulted in greater levels of cardiac malondialdehyde, a
      marker of lipid peroxidation, and a depressed index of myocardial antioxidant
      potential compared with all other groups (P<0.05). Hearts from the resistance
      training plus alcohol animals exhibited malondialdehyde and antioxidant levels
      similar to sedentary controls, suggesting that resistance training protected
      against the alcohol-induced myocardial stress. CONCLUSION: These results suggest
      that resistance training may attenuate the damaging effects of alcohol on the
      heart and preserve myocardial antioxidant capacity.

PMID- 16449868
TI  - Cardiac autonomic modulation during recovery from acute endurance versus
      resistance exercise.
AB  - BACKGROUND: The kinetics of parasympathetic reactivation after dynamic endurance
      exercise have been well elucidated. However, autonomic recovery of cardiac
      function after resistance exercise is not known. PURPOSE: The purpose of this
      study was to assess cardiac autonomic modulations during recovery from acute
      resistance exercise versus acute endurance exercise. METHODS: Electrocardiogram
      readings were collected before and 30 min after a single bout of endurance or
      resistance exercise in 14 male participants (aged 25.3+/-2.5 years). Heart rate
      (HR) variability was spectrally decomposed using an autoregressive approach. High
      frequency (HF) power was considered representative of vagal modulation. All
      values were expressed in both absolute and normalized units (normalized for
      change in total power). RESULTS: A mode-by-time interaction (P<0.05) was detected
      for HR, which remained elevated to a greater extent after resistance exercise.
      Total power was significantly reduced after resistance exercise (P<0.05) but not
      endurance exercise. An interaction (P<0.05) was also detected for both a change
      in absolute natural log function HF power and natural log function low frequency
      (LF) power (P<0.05), as both variables decreased more after resistance exercise.
      When normalized for changes in total power, interactions in LF and HF power were
      lost. The LF/HF ratio was significantly increased after both resistance and
      endurance exercise (P<0.05). CONCLUSION: Greater elevations in HR after acute
      resistance exercise versus acute endurance exercise may be related to greater
      reductions in cardiac parasympathetic tone.

PMID- 16449869
TI  - Serum albumin and self-reported prevalence of stroke: a population-based, cross
      sectional study.
AB  - BACKGROUND: Since information about the association between serum albumin and
      risk of stroke is limited the purpose of the present paper was to re-investigate
      this relationship. DESIGN: The study followed a cross-sectional design. METHODS:
      In the cross-sectional Norwegian Oslo Health Study the concentration of serum
      albumin and blood pressure was determined in a random sample of 5071 men and
      women, 30-75 years of age. Logistic regression was used to study the association
      between the serum albumin concentration and self-reported prevalence of stroke.
      In the sample there were 122 subjects with a history of stroke and 4949 subjects
      without. RESULTS: Low albumin (i.e. < or =47 versus >47 g/l) was associated with
      increased prevalence of self-reported stroke (odds ratio 1.83; 95% confidence
      interval, 1.20-2.78; P=0.005), after adjusting for age (< or =45 versus > or =59
      years) and sex. Including smoking, blood pressure and length of education into
      the model did not have any major influence on the result. CONCLUSION: Low serum
      albumin is associated with increased prevalence of self-reported stroke.

PMID- 16449870
TI  - Long-term influence of a health education programme on knowledge and health
      behaviour in children.
AB  - BACKGROUND: Aiming at an active lifestyle, healthy food habits and non-smoking
      among Swedish children, the Swedish Heart Lung Foundation initiated the health
      educational programme 'An adventure with Pelle Pump'. A study kit, including
      theoretical and practical material on heart-lung function and healthy behaviour,
      was offered to all fourth graders in Sweden. The impact of the programme was
      examined by studying health behaviours and health knowledge among programme
      participants using non-participants as a control population. METHODS: A
      questionnaire on health behaviour and health knowledge was answered by a random
      sample of 1369 children from different social classes and living conditions.
      Children subjected to the programme formed the programme group (n=523) and those
      without exposure served as a control group (n=846). RESULTS: Children in the
      programme group had a significantly higher level of knowledge (P<0.001) on
      questions relating to health behaviour and bodily functions. The actual health
      behaviour was, however, not affected by the programme. CONCLUSION: Children
      exposed to a health education programme had, compared with a control population,
      2 years after completing the programme, an increased level of knowledge; however,
      no difference was found in health behaviour.

PMID- 16449871
TI  - Apolipoprotein E polymorphism and preclinical carotid artery disease in untreated
      hypertensive men.
AB  - METHODS: The apolipoprotein E (apoE) polymorphism was evaluated alone, and in
      interaction with smoking status, in predicting carotid intima-medial thickness
      and plaque among 182 untreated, hypertensive, white men (mean age 56+/-8.9
      years). RESULTS: After covariate adjustment (age, education, smoking, body mass
      index, systolic and diastolic blood pressure, glucose, total : high-density
      lipoprotein), apoE genotype (no [epsilon]4 versus any [epsilon]4) predicted mean
      ([beta]=-0.139, P=0.023) and maximum ([beta]=-0.138, P=0.028) intima-medial
      thickness, as well as plaque ([beta]=-0.744; P=0.072). Tests of a genotype-x
      smoking interaction were non-significant. CONCLUSIONS: Mean intima-medial
      thickness was greater in men with the 3/3 than [epsilon]4 genotypes (2/4 3/4
      4/4), suggesting genetic risk for carotid atherosclerosis may be conferred by the
      [epsilon]3, rather than the [epsilon]4, allele.

PMID- 16449872
TI  - Hepatic lipase C-514T polymorphism and its association with high-density
      lipoprotein cholesterol level in Tehran.
AB  - BACKGROUND: The study was conducted to obtain the frequency of the hepatic lipase
      C-514T polymorphism and evaluate its relation with serum HDL cholesterol levels
      in Tehran. METHODS: A segment of the gene mentioned was amplified by polymerase
      chain reaction in 545 people and the restriction fragment length polymorphism
      revealed. RESULTS: The T allele frequency was 0.154. No significant relationship
      between HDL cholesterol levels and C-514T polymorphism was found even after
      adjusting for age, body mass index and blood pressure. CONCLUSION: The frequency
      of the polymorphism is similar to other Caucasian populations and no significant
      relationship exists between the non-CC genotype of the gene and a higher serum
      HDL cholesterol concentration.

PMID- 16449873
TI  - Assessing the quality of risk factor survey data: lessons from the WHO MONICA
      Project.
AB  - BACKGROUND AND PURPOSE: Survey data quality is a combination of the
      representativeness of the sample, the accuracy and precision of measurements,
      data processing and management with several subcomponents in each. The purpose of
      this paper is to show how, in the final risk factor surveys of the WHO MONICA
      Project, information on data quality were obtained, quantified, and used in the
      analysis. METHODS AND RESULTS: In the WHO MONICA (Multinational MONItoring of
      trends and determinants in CArdiovascular disease) Project, the information about
      the data quality components was documented in retrospective quality assessment
      reports. On the basis of the documented information and the survey data, the
      quality of each data component was assessed and summarized using quality scores.
      The quality scores were used in sensitivity testing of the results both by
      excluding populations with low quality scores and by weighting the data by its
      quality scores. CONCLUSIONS: Detailed documentation of all survey procedures with
      standardized protocols, training, and quality control are steps towards
      optimizing data quality. Quantifying data quality is a further step. Methods used
      in the WHO MONICA Project could be adopted to improve quality in other health
      surveys.

PMID- 16449874
TI  - Relationships between sports-specific characteristics of athlete's heart and
      maximal oxygen uptake.
AB  - BACKGROUND: Improvement to maximal oxygen uptake is mainly due to myocardial
      adaptations brought about by physical training. As a consequence, the athlete's
      heart echocardiographic modifications associated with these adaptations are
      already well-known. We studied the relationships between maximal oxygen uptake
      (ml/min) and resting echocardiographic patterns in three athlete groups. METHODS:
      Tumbling (n=16), canoeing (n=12), cycling (n=12) and untrained (n=19)
      participants performed clinical examination and an echocardiogram. Trained groups
      performed a maximal graded exercise test on a cycle ergometer with gas exchange
      analysis. RESULTS: Sport-specific cardiac hypertrophy was observed. No
      significant echocardiographic difference was noted between untrained and tumbling
      participants. Canoeists showed higher end-diastolic thickness of the
      interventricular septum (P<0.001) and left ventricle mass (P<0.05) than untrained
      and higher posterior wall thickness (P<0.001) and than untrained and tumbling
      participants. In comparison between untrained, tumbling and cycling participants,
      left ventricular end-diastolic diameter (P<0.001) and left ventricular mass
      (P<0.001) was higher in cyclists. In trained subjects studied as a global group,
      the main linear correlation with maximal oxygen uptake concerned left ventricular
      end-diastolic diameter (r=0.92; P<0.001), left ventricular mass (r=0.60; P<0.001)
      and to a lesser extent aortic (r=0.39; P<0.01) and left atrium (r=0.36; P<0.05)
      diameters and E (r=0.38; P<0.05) and A (r=-0.33; P<0.05) Doppler peak velocities.
      Each trained group showed specific correlations between echocardiographic
      parameters and absolute maximal oxygen uptake. No further correlation was noted
      with left ventricular end-diastolic diameter or left ventricle mass when each
      group was studied individually. CONCLUSIONS: In athletes, maximal oxygen uptake
      is partly linked to some resting echocardiographic parameters. Specific
      relationships between maximal oxygen uptake and some echocardiographic parameters
      in relation to the sport practised are also observed.

PMID- 16449875
TI  - Cardiac rehabilitation in England: a detailed national survey.
AB  - AIMS: The purpose of this study is to conduct a detailed analysis of cardiac
      rehabilitation programmes in England to compare actual provision with the
      recommendations of the National Service Framework and Scottish Intercollegiate
      Guideline Network guidelines. METHODS: Questionnaires and interviews were
      conducted with key staff from one centre in each Strategic Health Authority in
      England to establish staffing levels, patient throughput, programme details, data
      collection and funding. RESULTS: There were major discrepancies between
      programmes and the national recommendations. Perceptions of the service were
      often at variance within key staff in the trust. Staffing levels, lack of
      facilities and space were identified as a weakness in many of the programmes.
      Inadequate exercise sessions, poor record keeping and a failure to tailor the
      sessions to the patients needs were common. Mean funding was pound288 per patient
      rehabilitated. CONCLUSIONS: For those 30% of eligible patients who enter cardiac
      rehabilitation in England, the service suffers from inadequate staffing,
      facilities and space, associated with gross underfunding. If the recommended 85%
      of eligible patients were included the situation would be much worse. The
      Department of Health recommendations for cardiac rehabilitation have not been
      translated into action, with most hospitals giving it low priority compared with
      other cardiology services. A treatment with demonstrable benefits should at least
      meet the standards recommended by national guidelines.

PMID- 16449877
TI  - From the editor: ethics/integrity and trust.

PMID- 16449878
TI  - Guest editorial: ethics/integrity and trust: bridging the gaps.

PMID- 16449879
TI  - The ethical leader.
AB  - Ethics in healthcare organizations are the purview of not only bioethical
      committees healthcare but also management, which faces ethical dilemmas that are
      as difficult and many sided as are medical decisions faced by patients and their
      families. Leaders with integrity recognize that most issues have numerous
      stakeholders with varying points of view and make it part of their leadership
      competency to include consideration of ethics in their management decisions.

PMID- 16449881
TI  - Issues of trust and ethics in computerized clinical decision support systems.
AB  - Clinical decision support systems are computer technologies that model and
      provide support for human decision-making processes. Decision support mechanisms
      facilitate and enhance a clinician's ability to make decisions at the point of
      care. Decisions are facilitated through technology by using automated mechanisms
      that provide alerts or messages to clinicians about a potential patient problem.
      A clinician's level of trust in these technologies to support decision making is
      affected by how knowledge is represented in these tools, their ability to make
      reasonable decisions, and how they are designed. Furthermore, ethical tensions
      occur if these systems do not promote standards, if clinicians do not understand
      how to use these systems, and when professional relationships are affected.
      Issues of trust and ethical concerns will be examined in this article, using a
      research study of midwestern nursing homes that implemented a clinical decision
      support system.

PMID- 16449880
TI  - Strategic positioning for nursing excellence in health systems: insights from
      chief nursing executives.
AB  - The emergence of health systems as a dominant structure for organizing healthcare
      has stimulated the development of health system chief nursing executive (CNE)
      positions. These positions have large spans of control, requiring CNEs to balance
      a wide range of responsibilities, making them accountable for fiscal management,
      quality of care, compliance, and contributing to organizational growth. As such
      the CNE is required to use principles of distributive justice to guide priority
      setting and decision making. This review addresses important questions about CNE
      system integration strategies, strategic priorities, and organizational
      positioning as they attempt to fulfill their ethical responsibilities to patients
      and the nurses they serve.

PMID- 16449882
TI  - The fair factor in matters of trust.
AB  - Communities are bound together by trust among their members. Trust thrives when a
      pervasive sense of fairness exists. Evidence suggests that trust has social,
      professional, and economic value for today's organizations, making it worthy of
      attention. Matters of trust and justice are important and timely for nurse
      leaders to consider given the challenge to improve practice settings in a manner
      that enhances nurse satisfaction. The aim of this article is to make explicit the
      value in building organizational justice and trust within an organization's
      nursing community. Nursing leadership strategies are integrated, thus offering
      practical guidance in creating a culture of justice, making trust explicit, and
      establishing trustworthiness.

PMID- 16449883
TI  - An imperative to improve discharge planning: predictors of physical function
      among residents of a medicare skilled nursing facility.
AB  - Given the pressure to effects of shorter length of stay among older adults, it is
      important to understand factors that predict trajectories of physical function in
      a posthospital recovery period. Data were collected from the medical records of
      131 older adults following lower extremity surgery to identify admission factors
      that predict physical function at discharge, length of stay, and discharge
      disposition in a Medicare skilled nursing facility. Knowing on admission those
      who are most at risk for poor physical function at discharge can arm nurse
      administrators with critical information for better discharge planning for
      continuing services.

PMID- 16449884
TI  - Caring theory as an ethical guide to administrative and clinical practices.
AB  - This article explores the conventional relationship between caring, economics,
      and administrative practices that no longer serve patients, practitioners, or
      systems. A shift toward human caring values and an ethic of authentic healing
      relationships is required as systems now have to value human resources and life
      purposes, inner meanings, and processes for workers and patients alike, not just
      economics alone. This shift requires a professional ethos with renewed attention
      to practice that is ethics/values-based and theory-guided, alongside evidence and
      economics. Emergent professional, caring-theory-guided practice options are
      presented, which are grounded on this deeper ethical-moral and theoretical
      foundation for transforming the practitioners and the system.

PMID- 16449885
TI  - Ethical considerations for the utilization of tele-health technologies in home
      and hospice care by the nursing profession.
AB  - Home care, including hospice care, is a growing component of the current
      healthcare system and pertains to care services that are provided to individuals,
      their family members, and caregivers in their own residence. Both domains face
      funding limitations as life expectancy and the segment of the population older
      than 65 years increase. Tele-health, defined as the use of advanced
      telecommunication technologies to enable communication between patients and
      healthcare providers separated by geographic distance, is perceived as a concept
      that can enhance both home and hospice care and address some of the current
      challenges. This article discusses ethical challenges associated with the
      utilization of tele-health technologies by the nursing profession in the home
      setting. These factors form a framework for the ethical considerations that
      result from the introduction of these technologies in nursing practice.
      Specifically, the article discusses the issue of privacy and confidentiality of
      patient data, informed consent, equity of access, promoting dependency versus
      independence, the lack of human touch and the impact of technology on the nurse
      patient relationship, and the medicalization of the home environment. These
      issues constitute a road map both for nursing practitioners who are aiming to
      provide an efficient delivery of services in the home and for nursing
      administrators who are asked to make judgments about the use of tele-health
      technology as a supplement to traditional care and as a cost-saving tool.

PMID- 16449886
TI  - Addressing nurses' ethical concerns about research in critical care settings.
AB  - Clinical research with critically ill patients presents numerous ethical issues
      affecting patients' well-being, research integrity, and nursing practice. Key
      findings from a survey of critical care nurses' perceptions about research
      ethical issues in these settings indicated that nurses encounter ethical issues
      about which they have limited knowledge and they may not seek guidance from the
      most appropriate resources. The results suggest that nurses, as well as
      researchers, need not only training about the responsible conduct of research but
      also visible and highly functional organizational structures to support and
      oversee clinical research in research-oriented medical centers.

PMID- 16449887
TI  - Promoting respect for persons: developing a brochure for research participants.
AB  - The Institute of Medicine report Responsible Research: A Systems Approach to
      Protecting Research Participants noted that research participants require
      educational materials and ongoing interactions with investigators and healthcare
      professionals to have sufficient information to make a choice and be empowered to
      ask questions regarding their research participation. One of the ethical
      principles outlined in the Belmont Report, Respect for Persons, provided the
      framework for developing a brochure for research participants specific to the
      Department of Veterans Affairs (VA). The intent was to provide veterans and their
      families information about research in the VA and a list of basic questions to
      guide them through the complex decision making about their rights as research
      participants.

PMID- 16449888
TI  - Ethics and information technology: how nurses balance when integrity and trust
      are at stake.
AB  - When we think about ethics in nursing, such things as "Do Not Resuscitate" (DNR)
      orders and euthanasia come to mind. However, in the information age, there are
      some often-overlooked ethical issues surrounding information and information
      systems. This article examines several information technology influences and
      their impact on the issues of ethics, integrity, and trust.

PMID- 16449889
TI  - Quantitative analysis of changes in cervical intervertebral foramen size with
      vertebral translation.
AB  - STUDY DESIGN: Simulated translation of the C5 vertebra was performed in 20
      embalmed cadaveric cervical spines, and cross-sectional areas of the C4-C5 and C5
      C6 intervertebral foramina were measured and compared before and after
      translation of the C5 vertebra. OBJECTIVE: To determine the relationship of cross
      sectional intervertebral foraminal areas to the degrees of vertebral translation.
      SUMMARY OF BACKGROUND DATA: The common feature of clinical instability and
      adjacent diseases of the cervical spine is malalignment of the cervical spine
      (i.e., there is ventral and dorsal translation of vertebral body with respect to
      the adjacent upper and lower vertebral body, respectively). To our knowledge, no
      previous study has analyzed the quantitative effect of vertebral translation on
      the size of the intervertebral foramina. METHODS: The cross-sectional areas of
      the intervertebral foramina at C4-C5 and C5-C6 were measured on computerized
      tomography. The images were then transferred to the personal computer, where
      consecutive dorsal translations of C5 vertebrae with a 1-mm increment from 1 to 5
      mm displacements were performed using Microsoft paint software (Microsoft, Corp.,
      Redmond, WA). National Institutes of Health (Bethesda, MD) Image J software
      (V1.33m) was then used to measure the areas of both sides of C4-C5 and C4-C6
      foramina at normal and each displacement level in the computer. RESULTS:
      Following dorsal translation of C5 vertebra, anterolisthesis of C4 relative to C5
      and retrolisthesis of C5 relative to C6 was noted. No significant difference was
      found between the measured values using Aquarius Image software (Microsoft,
      Corp.) on computerized tomography and National Institutes of Health image J
      software on the desktop computer (P > 0.05). When compared with normal values,
      there was an increase in the C4-C5 intervertebral foraminal area (i.e., 6%, 14%,
      18%, 21%, and 26% with anterolisthesis of C4 relative to C5 following 1, 2, 3, 4,
      and 5-mm dorsal translation of the C5 vertebra, respectively). There was a 12%
      decrease in the C5-C6 intervertebral foraminal area, with each 1-mm incremental
      retrolisthesis of C5 relative to C6 vertebra. Statistically significant
      differences were found among residual cross-sectional foraminal areas following
      different degrees of dorsal translation (P < 0.05). CONCLUSION: There is a
      significant increase in size with anterolisthesis and decrease in size with
      retrolisthesis of upper and lower adjacent vertebral intervertebral foramina,
      respectively.

PMID- 16449891
TI  - Effects of pelvic skeletal asymmetry on trunk movement: three-dimensional
      analysis in healthy individuals versus patients with mechanical low back pain.
AB  - STUDY DESIGN: Comparative analysis and correlational research design were used to
      investigate the association between anthropometry and biomechanical performance
      among asymptomatic subjects and patients with low back pain (LBP). OBJECTIVES: To
      examine the association between pelvic asymmetry and patterns of trunk motion in
      asymptomatic and LBP subjects. Secondary objective was to investigate the
      association between restricted trunk motion, laterality of referred pain, and
      pelvic asymmetry. SUMMARY OF BACKGROUND DATA: Subtle pelvic asymmetry (exhibited
      as either lateral pelvic tilt or iliac rotational asymmetry), which is common
      among normal individuals, has not been convincingly linked to abnormalities in
      back movements. Given the difficulty in diagnosing most LBP, a classification
      using pelvic asymmetry and patterns of movement could be helpful in establishing
      a rational treatment plan. METHODS: Fifty-nine subjects with no history of LBP
      and 54 patients with mechanical unilateral LBP were tested. An anthropometric
      frame was used to measure pelvic asymmetry in standing. Dynamic motion data,
      comprised of the principal and coupled movements, were collected using the
      Qualysis Motion Capture System. RESULTS: While the groups did not differ in the
      total range of lumbar movement, the LBP group exhibited significantly higher
      asymmetry in the principal motion. The groups differed significantly in the
      pattern of coupled rotation during lateral flexion. Asymmetry in lumbar lateral
      flexion was highly related to two types of pelvic asymmetry: lateral pelvic tilt
      (LPT) and iliac rotation asymmetry (IRA). Asymmetry in lumbar axial rotation was
      highly related to IRA but weakly related to LPT. CONCLUSIONS: This study
      demonstrates objective differences in patterns of lumbar movement between
      asymptomatic subjects and patients with LBP. The study also demonstrates that
      subtle anatomic abnormality in the pelvis is associated with altered mechanics in
      the lumbar spine. We suggest that asymmetry of lumbar movement may be a better
      indicator of functional deficit than the absolute range of movement in LBP.

PMID- 16449890
TI  - Lumbar spinal disorders in patients with athetoid cerebral palsy: a clinical and
      biomechanical study.
AB  - STUDY DESIGN: Radiologic study for patients with athetoid cerebral palsy (CP),
      and a biomechanical study using the finite-element model (FEM). OBJECTIVES: To
      understand the lumbar disorders of athetoid CP patients and the etiology based on
      the results from the FEM study. SUMMARY OF BACKGROUND DATA: Cervical spondylotic
      myelopathy is a well-identified spinal disorder associated with cerebral palsy,
      especially in athetoid type. One can rationalize that the athetoid involuntary
      trunk movement may induce stress-related lumbar disorders. Until now, very few
      investigations have been conducted on lumbar disorders that could occur in
      patients with CP. METHODS: Sixty-one cases with athetoid cerebral palsy were
      clinically reviewed. Radiographs of the lumbar spine in 30 cases with low back
      pain were taken. From these radiographs, the incidence of lumbar spondylolysis
      and endplate lesion was analyzed. The biomechanical study was conducted using a
      three-dimensional FEM of the ligamentous lumbar spine. Axial compression of 400 N
      was applied to simulate preload on the spine during the standing position
      followed with 10.6 Nm moment to simulate extension and axial rotation. The
      combined motion of extension and axial rotation was also simulated. During supine
      position, pure extension and rotation were simulated, and no preload was applied.
      The von Mises stresses were computed at the pars interarticularis at the each
      level and compared for different motions. RESULTS: Among the 61 patients, 41
      complained of symptoms such as low back and leg pain. Thirty of these 41 patients
      gave their consents to undergo radiographic evaluation. Twenty-eight of the 30
      patients (93.3%) showed stress-related disorders such as the spondylolysis and/or
      vertebral endplate lesions. Spondylolysis was found in 18 of the 30 patients
      (60.0%). Spondylolysis was observed at the multiple levels in 4 patients
      involving two levels in 2 cases and three levels in the other 2 cases. Vertebral
      endplate lesions (deformity) were seen in 26 (86.7%) of the 30 patients. Overall,
      the lesions (deformity) were found in 109 of 330 endplates (33.0%) out of all
      lumbar endplates in the 30 patients. The FEM based results showed that stresses
      at pars interarticularis of L5 were the highest of all levels in all loading
      modes, with or without preload. However, compared with the extension or axial
      rotation alone modes, the combined motion of extension and rotation showed higher
      stresses at the pars interarticularis. CONCLUSIONS: The athetoid involuntary
      movements in CP patients may cause stress-related lumbar disorders. Especially,
      combined extension and rotation due to the involuntary trunk motion may
      contribute to the high incidence of spondylolysis.

PMID- 16449892
TI  - Automatic measurement of vertebral rotation in idiopathic scoliosis.
AB  - STUDY DESIGN: Development of an automatic measurement algorithm and comparison
      with manual measurement methods. OBJECTIVES: To develop a new computer-based
      method for automatic measurement of vertebral rotation in idiopathic scoliosis
      from computed tomography images and to compare the automatic method with two
      manual measurement techniques. SUMMARY OF BACKGROUND DATA: Techniques have been
      developed for vertebral rotation measurement in idiopathic scoliosis using plain
      radiographs, computed tomography, or magnetic resonance images. All of these
      techniques require manual selection of landmark points and are therefore subject
      to interobserver and intraobserver error. METHODS: We developed a new method for
      automatic measurement of vertebral rotation in idiopathic scoliosis using a
      symmetry ratio algorithm. The automatic method provided values comparable with
      Aaro and Ho's manual measurement methods for a set of 19 transverse computed
      tomography slices through apical vertebrae, and with Aaro's method for a set of
      204 reformatted computed tomography images through vertebral endplates. RESULTS:
      Confidence intervals (95%) for intraobserver and interobserver variability using
      manual methods were in the range 5.5 degrees to 7.2 degrees . The mean (+/-SD)
      difference between automatic and manual rotation measurements for the 19 apical
      images was -0.5 degrees +/- 3.3 degrees for Aaro's method and 0.7 degrees +/- 3.4
      degrees for Ho's method. The mean (+/-SD) difference between automatic and manual
      rotation measurements for the 204 endplate images was 0.25 degrees +/- 3.8
      degrees . CONCLUSIONS: The symmetry ratio algorithm allows automatic measurement
      of vertebral rotation in idiopathic scoliosis without intraobserver or
      interobserver error due to landmark point selection.

PMID- 16449893
TI  - Arterial injury following percutaneous vertebral augmentation: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a case of injury to a segmental
      branch of the L4 lumbar artery following kyphoplasty. SUMMARY OF BACKGROUND DATA:
      To our knowledge, arterial injury following vertebral augmentation has not been
      described. The complications that have been reported rarely require additional
      intervention. The caliber of the fourth lumbar artery is such that injury to it,
      or to its more proximal branches, may cause significant morbidity. METHODS: An 84
      year-old female who presents 10 days after surgery from L5 kyphoplasty with
      pulsatile bleeding from the kyphoplasty site. An angiogram revealed an injury to
      a segmental branch of L4 lumbar artery. RESULTS: A superselective angiogram was
      performed, followed by embolization of a branch of the L4 lumbar artery. This
      procedure successfully controlled the bleeding. CONCLUSION: Surgeons performing
      percutaneous procedures for the augmentation of vertebral compression fractures
      are not able to visualize the arterial channels on the posterior aspect of the
      vertebral column. Although injury to these structures may be difficult to
      prevent, awareness of this complication will improve our response and decrease
      associated morbidity.

PMID- 16449894
TI  - Epidural varix at the cervicothoracic junction: unusual cause of quadriplegia: a
      case report.
AB  - STUDY DESIGN: A case report describing an unusual incident of quadriplegia in a
      young adult male caused by an epidural varix at the cervicothoracic junction.
      OBJECTIVE: To report an unusual case of quadriplegia caused by an epidural varix
      at the cervicothoracic junction. SUMMARY OF BACKGROUND DATA: Epidural varices are
      dilated tortuous elongated veins inside the central canal. In degenerative spinal
      stenosis, these varices are a result of venous stagnation and contribute to the
      pathogenesis of radicular pain. In the absence of stenosis, primary varicosities
      develop as a result of dynamic obstruction to venous outflow during spinal
      movements. A primary epidural varix can produce neurologic deficit similar to a
      space occupying lesion within the spinal canal. The myeloradiculopathy is of a
      slow progressive nature. MATERIAL AND METHODS: A young man presented with an
      acute onset flaccid quadriplegia in the absence of significant trauma. Magnetic
      resonance imaging revealed an extradural space occupying lesion at the
      cervicothoracic junction that was diagnosed as an isolated epidural varix during
      surgery. RESULTS: No neurologic recovery occurred. Postoperative magnetic
      resonance imaging revealed a syrinx in the cervicothoracic cord. CONCLUSION: In
      the absence of other precipitating factors, the cord injury was attributed to the
      epidural varix. A temporary impedance to the venous outflow with the increase in
      the venous pressure has been hypothesized as the mechanism of cord injury.

PMID- 16449896
TI  - End organ effects of high-dose human equivalent methylprednisolone in a spinal
      cord injury rat model.
AB  - STUDY DESIGN: Interventional study. OBJECTIVE: To analyze the histologic effects
      of high-dose human equivalent methylprednisolone on the pulmonary, cardiac,
      intestinal, renal, hepatic, and splenic tissues in a spinal cord injury rat
      model. SUMMARY OF BACKGROUND DATA: There are numerous investigations of various
      medical interventions for the treatment of acute spinal cord trauma. Currently,
      the only generally accepted medical intervention in an acute spinal cord trauma
      is the intravenous administration of high doses of methylprednisolone. Although
      it has been nearly 2 decades since the first National Acute Spinal Cord Injury
      Study investigated the role high-dose steroids might play in the treatment of
      acute spinal cord trauma, controversy still exists regarding the efficacy of this
      treatment. To our knowledge, no study has examined the role of high-dose
      methylprednisolone in organ systems other than the spinal cord in an acute spinal
      cord injury model at the histologic level. This study attempts to characterize
      end organ histologic response to human dose equivalent (HDE) intravenous
      methylprednisolone administration in a rodent model of acute spinal cord injury.
      METHODS: A total of 48 Sprague-Dawley rats were divided equally into control and
      experimental groups. Each group was subdivided into 6 sets of 4 animals each,
      according to intervals after injury. Groups 1-6 consisted of animals euthanized
      at 0, 4, 8, 16, 24, and 48 hours after spinal cord injury. Paraplegia after lower
      thoracic laminectomy was achieved using a standardized Allen weight drop
      technique. Within 1 hour of injury, experimental animals were treated with HDE
      methylprednisolone, infused for 23 hours continuously. Liver, kidney, lung,
      intestine, spleen, and heart were harvested at variable intervals after injury
      and prepared for histologic examination. These slides were analyzed with
      microscopic staining techniques and compared in a blinded manner by a qualified
      pathologist. RESULTS: Of all the end organs analyzed, the spleens were most
      affected. Lymphocytic depletion was seen in as little as 4 hours after
      methylprednisolone infusion and continued until 48 hours. Pulmonary tissues
      variably showed interstitial congestion and eosinophilic alveolar collections.
      Intestinal mucosal tissues showed edema and autolyzed mucosa from 16 hours
      onwards. Cardiac, kidney, and hepatic tissue did not differ significantly from
      controls. CONCLUSIONS: Histologically, HDE methylprednisolone caused significant
      splenic lymphocytic depletion changes in as little as 4 hours. This trend of end
      organ lymphocytopenia continued to progress until 48 hours. Pulmonary
      eosinophilic infiltrates were seen from 8 until 24 hours. Intestinal mucosal
      edema and necrosis were seen in samples at 16 hours throughout 48 hours. This
      study was designed to evaluate end organ changes seen in an animal model of an
      acute spinal cord injury treated with HDE methylprednisolone. Study animals were
      infused with HDE methylprednisolone given according to the National Acute Spinal
      Cord Injury Study II protocol. The kidney, lung, cardiac, intestinal, splenic,
      and hepatic tissues from the aforementioned animals were then sectioned and
      analyzed using histologic staining techniques by a qualified pathologist.

PMID- 16449897
TI  - Three-dimensional analysis of 2 fusionless scoliosis treatments: a flexible
      ligament tether versus a rigid-shape memory alloy staple.
AB  - STUDY DESIGN: Experimental scoliosis was created and subsequently corrected in
      goats. The 3-dimensional (3-D) effects of the treatments were analyzed.
      OBJECTIVE: To analyze the 3-D effect of 2 different fusionless scoliosis
      treatment techniques on an experimental idiopathic-type scoliosis using plain
      radiographs and computerized tomography. SUMMARY OF BACKGROUND DATA: Scoliosis is
      a complex 3-D spinal deformity with limited treatment options. By preserving
      growth, motion, and function of the spine, fusionless scoliosis surgery provides
      theoretical advantages over current forms of treatment. METHODS: Scoliosis was
      created in 24 Spanish cross-X female goats using a flexible, left posterior
      asymmetric tether from the T5 to L1 laminae, with convex rib resection and
      concave rib tethering from T8 to T13. After 8 weeks of posterior tethering, goats
      were randomized into 3 treatment groups: group 1, no treatment; group 2, anterior
      shape memory alloy staple; and group 3, anterior ligament tether with bone
      anchor. The 6 levels of maximal curvature were instrumented in groups 2 and 3.
      All goats were observed for an additional 12-16 weeks. Serial radiographs and
      computerized tomography were used to document progression/correction of coronal,
      sagittal, and transverse plane deformities throughout the study. RESULTS: There
      were 20 goats that had progressive, structural, idiopathic-type, lordoscoliotic
      curves convex to the right in the thoracic spine over the 8-week tethering
      period. An overall deformity score equaling the sum of the scoliosis, lordosis,
      and axial rotation measurements was calculated for each goat at 3 times.
      CONCLUSION: The data in this study show the ability of a ligament tether attached
      to a bone anchor to correct scoliosis modestly in the coronal plane, but not in
      the sagittal or transverse plane. In addition, although a significant decrease in
      the deformity score was shown initially in this group (P < 0.001), the effect was
      lost over time. The final deformity in the bone anchor/ligament tether group
      wassignificantly less than either the stapled or untreated groups (P < 0.03).
      Further study is warranted to provide a better understanding of the 3-D effects
      of fusionless scoliosis treatments.

PMID- 16449898
TI  - Anatomic reduction and monosegmental fusion in high-grade developmental
      spondylolisthesis.
AB  - STUDY DESIGN: A retrospective review of the clinical and radiographic outcomes of
      reduction by temporary instrumentation of L4 and monosegmental fusion of L5/S1 in
      patients with high-grade developmental spondylolisthesis. OBJECTIVE: To assess
      the efficacy of this technique in the reduction of local deformity and correction
      of overall sagittal profile. SUMMARY OF BACKGROUND DATA: In situ fusions as well
      as partial reduction with fusion L4-S1 via various approaches have been described
      previously. To date and to our knowledge, there have been no reports describing
      complete reduction and monosegmental fusion for high-grade developmental
      spondylolisthesis. METHODS: A total of 27 consecutive patients with severe
      developmental spondylolisthesis of L5/S1 were treated with operative reduction
      via temporary instrumentation of L4 and monosegmental fusion of L5/S1. The
      clinical and radiographic outcomes were retrospectively reviewed for each case at
      a minimum of 2 years (mean follow-up of 45 months; range 24-80). Mean age at
      surgery was 16.7 years (range 9-29). RESULTS: At most recent follow-up, 23
      patients were pain free. There were 4 patients who had moderate pain. All
      radiographic parameters improved. Mean slippage improved from 74.0% before
      surgery to 11.0% after surgery and 10.0% at latest follow-up. Slip angle improved
      from 36.6 degrees before surgery to 8.1 degrees after surgery and 7.6 degrees at
      latest follow-up. Sacral inclination improved from 34.6 degrees before surgery to
      43.4 degrees after surgery and 47.2 degrees at latest follow-up. The overall
      sagittal profile improved dramatically. There was 1 superficial infection, 6
      patients had L5 root symptoms (5 of these resolved, 1 patient had a persistent
      sensory deficit). Four patients had decompensation at L4/5 (2 reoperations).
      CONCLUSIONS: Reduction of L5/S1 with temporary instrumentation of L4 and
      monosegmental fusion of L5/S1 is an effective technique for the treatment of high
      grade developmental spondylolisthesis. A complete reduction of local deformity
      and excellent correction of overall sagittal profile can be achieved. Fusion of
      the primarily healthy segment L4/5 can be avoided.

PMID- 16449899
TI  - Spinal range of motion, muscle endurance, and back pain and function at least 20
      years after fusion or brace treatment for adolescent idiopathic scoliosis: a case
      control study.
AB  - STUDY DESIGN: A consecutive series of patients with adolescent idiopathic
      scoliosis (AIS), treated between 1968 and 1977 before 21 years of age with either
      distraction and fusion using Harrington rods (ST, n = 156; 145 females and 11
      males) or with brace (BT, n = 127; 122 females and 5 males), were followed at
      least 20 years after completion of the treatment. OBJECTIVES: To determine the
      long-term outcome in terms of spinal mobility and muscle strength and its
      possible correlations to present back pain and function in patients surgically or
      brace treated for AIS. SUMMARY OF BACKGROUND DATA: Few reports on long-term
      outcome on these variables have previously been presented for this group of
      patients. METHODS: A total of 135 (87%) of ST and 102 (80%) of BT patients
      underwent a complete examination by two unbiased observers incl. evaluation of
      lumbar muscle endurance and spinal mobility, curve size (Cobb method), validated
      questionnaires in terms of general and disease-specific quality of life aspects,
      as well as present back function and pain. An age- and sex-matched control group
      of 100 persons was randomly selected and subjected to the same examinations.
      RESULTS: For both ST and BT groups, lumbar spinal motion as well as muscle
      endurance were significantly decreased compared with controls. For ST patients,
      better lumbar extensor and flexor muscle endurance or lumbar spinal mobility
      correlated with a better physical function. The length of fusion into the lumbar
      spine correlated inversely with lumbar range of motion, but the finger-floor
      distance was not affected. BT patients with reduced lumbar spinal mobility
      experienced lumbar back pain more often than controls. CONCLUSIONS: For both
      brace treated and surgically treated AIS patients, spinal mobility and muscle
      endurance were reduced more than 20 years after completed treatment. The physical
      function was not severely restricted.

PMID- 16449900
TI  - Effects on lung function of multiple expansion thoracoplasty in children with
      thoracic insufficiency syndrome: a longitudinal study.
AB  - STUDY DESIGN: Longitudinal study of intraoperative pulmonary function in young
      children with thoracic hypoplasia and scoliosis undergoing multiple expansion
      thoracoplasty using the vertical expandable prosthetic titanium ribs (VEPTRs).
      OBJECTIVE: To test the long-term efficacy of VEPTR multiple expansion
      thoracoplasty. SUMMARY OF BACKGROUND DATA: To our knowledge, no direct
      measurements of pulmonary function have been reported with VEPTR expansion
      thoracoplasty. METHODS: There were 10 children with thoracic insufficiency
      syndrome, secondary to thoracic hypoplasia with progressive scoliosis, studied. A
      mobile pulmonary function laboratory unit was used to study forced vital capacity
      (FVC), maximum expiratory flow volume curves, and respiratory system compliance
      (Crs) with the patient under general anesthesia immediately before and after
      expansion thoracoplasty. Studies were repeated every 6 months at each subsequent
      operation for expansion thoracoplasty for the duration up to 33 months. RESULTS:
      At the baseline studies, FVC showed a moderate-to-severe decrease (69% of
      predicted values), indicating the presence of significant restrictive lung
      defect. Only 1 of 10 children had severe airway obstruction. The baseline Crs was
      markedly decreased in part because of the presence of significant atelectasis.
      Crs increased with an average of 42% after repeated hyperinflation (deep sighs).
      There was no change in lung volume or function immediately before versus after
      completion of expansion thoracoplasty. FVC increased significantly over time,
      with an average rate of 26.8% per year, the rate of increase similar to that of
      healthy children of comparative ages. In terms of percent-predicted values, FVC
      did not change significantly between the baseline and last test, indicating that
      in most children studied, lung growth kept up with body growth. CONCLUSION:
      Although it is difficult to assess the extent of the efficacy without a proper or
      historical control group for comparison, the present study indicates that in
      children with severe thoracic insufficiency syndrome, the insertion of VEPTRs
      with multiple expansion thoracoplasties is beneficial over time, by allowing the
      lungs to expand with body growth without further deterioration in lung function.

PMID- 16449902
TI  - Distal junctional kyphosis of adolescent idiopathic thoracic curves following
      anterior or posterior instrumented fusion: incidence, risk factors, and
      prevention.
AB  - STUDY DESIGN: This is a retrospective multicenter analysis of a subset of 375
      patients with thoracic adolescent idiopathic scoliosis (AIS) treated with either
      anterior (238) or posterior (137) fusion with preoperative or postoperative
      distal junctional kyphosis (DJK) >or=10 degrees . OBJECTIVES: To determine the
      incidence of DJK before and after surgery in patients with AIS undergoing either
      anterior or posterior thoracic fusion, and provide recommendations for
      prevention. SUMMARY OF BACKGROUND DATA: DJK following surgical treatment for AIS
      may result in pain, imbalance, and unacceptable deformity. The true incidence of
      DJK following selective anterior or posterior instrumentation and fusion is
      unknown, as are "risk factors" for its development. METHODS: Mean age at surgery
      was 14.4 years (range 9.1-20.9) in the anterior group and 14.7 years (range 10.2
      20.7) in the posterior. Analysis included the Cobb and instrumented levels of the
      thoracic curves, and sagittal measurements, all on preoperative and 2-year follow
      up standing 36-in radiographs. RESULTS: In the anterior group, the incidence of
      preoperative DJK was 4.2%, and postoperative DJK was 7.1%. In the posterior
      group, the incidence of preoperative DJK was 5.0% and 14.6% after surgery. When
      postoperative DJK developed in the posterior group, mean postoperative T10-L2 was
      +17 degrees kyphosis compared to +2 degrees in the posterior group without DJK (P
      < 0.001). When postoperative DJK developed in the anterior group, mean
      postoperative T10-L2 was +12 degrees kyphosis compared to +2 degrees for the
      anterior group without DJK (P = 0.006). DJK was significantly more likely to
      occur in the posterior group if the Cobb was instrumented to less than Cobb +1 (P
      < 0.001). CONCLUSIONS: It appears that both posterior and anterior
      instrumentation for thoracic curves must include the junctional level to prevent
      postoperative DJK when postoperative DJK is present. The presence of increased
      kyphosis after surgery in the T10-L2 region seen in both anterior and posterior
      groups that had postoperative DJK develop constitutes a "risk factor" for the
      development of DJK.

PMID- 16449901
TI  - Comparative analysis of pedicle screw versus hybrid instrumentation in posterior
      spinal fusion of adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective matched cohort study. OBJECTIVE: To comprehensively
      compare the 2-year postoperative results of posterior correction and fusion with
      segmental pedicle screw instrumentation versus with hybrid (proximal hooks and
      distal pedicle screws) constructs in adolescent idiopathic scoliosis (AIS)
      treated at a single institution. SUMMARY OF BACKGROUND DATA: Despite the reports
      of satisfactory correction and maintenance of scoliotic curves by pedicle screw
      instrumentation, there have been no reports on the comprehensive comparison of
      AIS treatment after segmental pedicle screw instrumentation versus hybrid
      instrumentation. MATERIALS AND METHODS: A total of 58 AIS patients that underwent
      posterior fusion with hybrid instrumentation (29) or pedicle screw (29)
      instrumentation at a single institution were sorted and matched according to four
      criteria: similar patient age, fusion levels, identical Lenke curve type, and
      identical operative methods. Patients were compared at 2-year follow-up according
      to radiographic changes, operative time, intraoperative blood loss, pulmonary
      function tests, and SRS-24 outcome scores. RESULTS: The two cohorts were well
      matched. The preoperative major Cobb angle averaged 62 degrees in the screw group
      and 60 degrees in the hybrid group. Average major curve correction was 70% in the
      screw group and 56% in the hybrid group (P = 0.001). At 2-year follow-up, major
      curve correction was 65% and 46%, respectively (P < 0.001). At 2-year follow-up,
      thoracic sagittal Cobb angle changes between T5 and T12 were 9.0 degrees decrease
      in the screw group and 2.4 degrees decrease in the hybrid group compared with
      preoperative (P = 0.024). There were no differences in the lowest instrumented
      vertebra below the lower end vertebra (P = 0.56), operative time (P = 0.14), and
      average estimated blood loss (P = 0.54). Two years following surgery, the screw
      group demonstrated improved percent predicted pulmonary function values compared
      with that of the hybrid group (FVC; 81% --> 81% in screw group vs. 85% --> 79% in
      hybrid group P = 0.08, FEV1; 73% --> 79% in screw group vs. 79% --> 75% in hybrid
      group, P = 0.006). Postoperative total SRS-24 scores were similar in both groups
      (hybrid group: 99 vs. screw group: 95) (P = 0.19). There were no neurologic
      complications related to hybrid or pedicle screw instrumentation. CONCLUSION:
      Pedicle screw instrumentation offers a significantly better major curve
      correction and postoperative pulmonary function values without neurologic
      problems compared with hybrid constructs. Both instrumentation methods offer
      similar junctional change, lowest instrumented vertebra, operative time, and
      postoperative SRS-24 outcome scores in the operative treatment of AIS.

PMID- 16449903
TI  - Minimum 5-year analysis of L5-S1 fusion using sacropelvic fixation (bilateral S1
      and iliac screws) for spinal deformity.
AB  - STUDY DESIGN: Clinical radiographic and outcomes investigation. OBJECTIVE: To
      investigate clinical and radiographic outcomes for lumbosacral fusion (in
      patients with spinal deformity) using a combination of bilateral sacral and iliac
      screws with a minimum 5-year follow-up. SUMMARY OF BACKGROUND DATA: To our
      knowledge, long-term results (>5 years of follow-up) of bilateral S1
      screw/bilateral iliac screw fixation have never been published or presented.
      MATERIALS AND METHODS: A total of 67 patients (from an initial consecutive cohort
      of 81) undergoing lumbosacral fusion with bilateral sacral and iliac screws with
      a minimum follow-up of 5 years (range 5-10 + 5, average 6 + 3) were analyzed for
      radiographic outcome and clinical course by an outcome questionnaire
      (administered at ultimate follow-up) analysis. Patients were divided into 2
      groups: group 1, 34 patients with mostly high-grade spondylolisthesis; and group
      2, 33 with adult scoliosis fused mostly from the thoracic spine to the sacrum. A
      true anteroposterior pelvis film was obtained in all patients to assess for
      sacroiliac joint arthritis, as were standard spine radiographs. Patients were
      administered Oswestry and directed buttock pain questionnaires at latest follow
      up. RESULTS: There were no cases of sacral screw failure (i.e., screw loosening,
      partial screw pullout, or fracture of the sacral screw). There were 5 cases of
      nonunion at L5-S1. Of the 5 cases, 3 did not have anterior column support at L5
      S1. Four of the 5 cases were revised, and, subsequently, 3 achieved union. Iliac
      screws were removed electively on 1 or both sides in 23 of the patients after 2
      years postoperatively because of prominence. There were 7 cases of iliac screw
      breakage. Iliac screw halos were observed in 29 patients. No sacroiliac
      osteoarthritis was observed on the true anteroposterior pelvis films. At ultimate
      follow-up, average visual analog painscale (0-10) score to assess buttock pain
      was 2.4, and average Oswestry score was 20.1. CONCLUSIONS: For high-grade
      spondylolisthesis and long adult deformity fusions to the sacrum, a montage of
      bilateral S1 screws and iliac screws were effective in protecting the sacral
      screws from failure. Pseudarthrosis at L5-S1 was manifested by rod breakage at
      that level. We saw no evidence of a long-term effect of the iliac screws
      predisposing the sacroiliac joints to degeneration at follow-up ranging from 5 to
      10 years.

PMID- 16449904
TI  - The effect of scoliosis fusion on spinal motion: a comparison of fused and
      nonfused patients with idiopathic scoliosis.
AB  - STUDY DESIGN: Movement analysis of spinal motion. OBJECTIVE: To compare spinal
      motion among females with normal spines, those with idiopathic scoliosis who had
      not had spinal fusion, and those who had undergone fusion for idiopathic
      scoliosis. SUMMARY OF BACKGROUND DATA: Previous reports have documented loss of
      spinal motion following fusion for idiopathic scoliosis in adolescents and
      adults. To our knowledge, comparison to control groups both with and without
      scoliosis that have not had spinal fusions has not been performed to date.
      METHODS: A total of 91 females between the ages of 15 and 28 years underwent
      computerized movement analysis. There were 34 fused patients, 32 unfused
      patients, and 25 healthy controls. The fused patients were divided into 3 groups:
      (1) 21 patients who had thoracic fusions that extended distally to T11, T12, or
      L1; (2) 6 patients with thoracic fusions ending at L2; and (3) 7 patients with
      thoracolumbar or lumbar fusions extending to L3 or L4. Marker triads were placed
      at C7-T1, T12-L1, and on the pelvis. Forward bend, extension, and left and right
      lateral bend were measured and divided into thoracic and lumbar motion. RESULTS:
      There was no difference in any motion between the control and unfused groups.
      There was overall 25% less total spinal motion in the surgical groups compared to
      the unfused group. Patients who had thoracic fusions had diminished thoracic
      motion, especially lateral bending, whereas those who had lumbar fusions had the
      least lumbar motion, particularly on forward bend and lateral bend maneuvers.
      There was no compensatory hypermobility of the unfused segments in the surgical
      group. CONCLUSIONS: Diminished spinal motion can be measured in patients who have
      had spinal fusions. Although stiffness in the operated curves should be expected,
      compensatory hypermobility in the unfused segments does not occur, resulting in a
      net loss of flexibility compared to controls.

PMID- 16449905
TI  - Spontaneous correction and derotation of secondary curves after selective
      anterior fusion of idiopathic scoliosis.
AB  - STUDY DESIGN: Clinical, rasterstereographic, and radiographic evaluation of
      spontaneous vertebral derotation of secondary curves in idiopathic scoliosis
      following selective anterior correction and fusion of the primary curve.
      OBJECTIVE: To quantify spontaneous vertebral derotation in secondary curves after
      selective anterior correction with attention to cosmetic outcome. SUMMARY OF
      BACKGROUND DATA: While the derotational effect of anterior instrumentation
      techniques on the instrumented curve is well understood, there is a paucity on
      data of the rotational behavior of the noninstrumented secondary curves. METHODS:
      A total of 43 patients with idiopathic scoliosis (16 with thoracic curves in
      group 1 and 27 with thoracolumbar/lumbar curves in group 2) underwent selective
      anterior instrumentation. Vertebral rotation was analyzed before surgery and, on
      average, 20 months after surgery using digital radiometric rotation analysis,
      back shape analysis with rasterstereography, and scoliometer measurement.
      RESULTS: In Group 1, there was a significant spontaneous vertebral derotation of
      the secondary lumbar curves by 14.2% (range from 12.7 degrees to 10.9 degrees) in
      the digital radiometric rotation analysis, surface derotation amounted to 49%
      (range from 9.6 degrees to 4.9 degrees) in the rasterstereography, and to 70% in
      the clinical scoliometer measurement (range from 8.0 degrees to 2.4 degrees ). In
      group 2, there was an increase of rotation of the noninstrumented secondary
      thoracic curves by 30% (range from 5.0 degrees to 6.5 degrees ) in digital
      radiometry, by 32.9% in the rasterstereography (range from 8.5 degrees to 11.3
      degrees), and a 28.3% increase in scoliometer measurement (range from 6.0 degrees
      to 7.7 degrees). CONCLUSION: Selective anterior instrumentation and fusion of
      primary thoracic curves results in satisfactory spontaneous vertebral and high
      surface derotation of the secondary lumbar curves. However, in primary
      thoracolumbar or lumbar curves, an increase of both vertebral and surface
      rotation of the secondary thoracic curve was noted. This increase can impair
      cosmetic outcome.

PMID- 16449907
TI  - Generalized osteopenia in adolescent idiopathic scoliosis--association with
      abnormal pubertal growth, bone turnover, and calcium intake?
AB  - STUDY DESIGN: A cross-sectional study in girls with adolescent idiopathic
      scoliosis (AIS) and healthy counterparts of similar age. OBJECTIVES: To study the
      association of bone mass with anthropometric parameters, bone turnover, and
      calcium intake in 621 girls with AIS, aged 11-6-years, and compare the results
      with 300 healthy girls of similar age. SUMMARY OF BACKGROUND DATA: Generalized
      low bone mass has been documented in AIS, yet the cause of low bone mineral
      density in AIS is unknown. METHODS: Corrected height and arm span, bone mineral
      density and bone mineral content of proximal femur, lumbar spine, and distal
      tibia, and bone turnover markers (bone alkaline phosphatase [bALP] and
      deoxypyridinoline) were evaluated. RESULTS: From age 13 years and older, the AIS
      group had longer anthropometric parameters (P < 0.05), generalized lower bone
      mass (P < 0.035), and 38.6% higher in bALP (P < 0.004) when compared with
      controls. A stronger inverse correlation between bALP and bone mass was noted in
      the AIS group. The bALP was positively correlated with bone area of tibia (P =
      0.013) in the AIS group only. Deoxypyridonine of the AIS group was not different
      from the controls until age 15 years. The mean calcium intake of the AIS group
      was very low (only 361 mg/day), and calcium intake was significantly associated
      with bone mass in the AIS group. Low bone mass in AIS could be explained by
      faster anthropometric bone growth, higher bone turnover, and lower calcium intake
      in multiple regression analysis. CONCLUSIONS: Results from the current study
      showed that an abnormally faster growth rate and higher bone turnover in the
      patient with AIS might lead to increased bone dimensions. Calcium intake in
      patients with AIS was very low and likely to be insufficient for normal bone
      mineralization. Therefore, low bone mass in AIS may result from abnormal bone
      mineralization qualitatively and quantitatively and, thus, fails to catch up with
      increased bone growth during the peripubertal period.

PMID- 16449906
TI  - Geometric and electromyographic assessments in the evaluation of curve
      progression in idiopathic scoliosis.
AB  - STUDY DESIGN: The natural history of patients with idiopathic scoliosis was
      analyzed radiographically and electromyographically in a prospective longitudinal
      study. OBJECTIVES: To identify changes in geometric variables and the sequence in
      which these changes occur during curve progression in the natural history of
      patients with idiopathic scoliosis. In addition, to study the relationship
      between several geometric variables and electromyographic (EMG) measurements to
      determine their predictive value as risk factors to curve progression of the
      scoliotic deformity. SUMMARY OF BACKGROUND DATA: The main area of concern in
      treating children with adolescent idiopathic scoliosis is the unpredictability of
      curve progression during the early development of the deformity. METHODS: The
      changes in radiographic geometric and EMG variables between the first
      presentation and consecutive 4-6-month follow-up periods were analyzed in 105
      patients with idiopathic scoliosis. Statistical analyses were performed to
      elucidate in more detail how spinal geometry evolves during curve progression.
      RESULTS: Curve severity was associated with remaining growth potential expressed
      as an increasing spinal growth velocity (SGV). With increasing SGV, an enhanced
      EMG activity at the lower part on the convex side of the curve expressed as EMG
      ratio was found. High EMG ratio was associated with increased axial rotation and
      diminished kyphosis before the rapid increase in Cobb angle. Lateral deviation,
      wedge angle, and axial rotation all increased during periods of progression.
      Changes in tilt angle and lordosis were not associated with curve progression.
      CONCLUSIONS: In the natural history of idiopathic scoliosis, SGV and EMG ratio at
      the lower end vertebra are prominent risk factors of curve progression. The
      asymmetric muscle activity is associated with increased axial rotation, which in
      its turn is associated with increasing Cobb angle and diminishing kyphosis. The
      combination of these variables provides insight in the physiologic and 3
      dimensional biomechanical evolution of the natural history of curve progression
      in idiopathic scoliosis.

PMID- 16449908
TI  - The objective determination of compliance in treatment of adolescent idiopathic
      scoliosis with spinal orthoses.
AB  - STUDY DESIGN: Prospective study using a specifically developed microelectronic
      technology. OBJECTIVE: To establish new technical methods for the objective
      measurement of brace use without patient involvement. SUMMARY OF BACKGROUND DATA:
      Effectiveness of spinal bracing clearly depends on the compliance of the patient.
      For further improvement of spinal bracing, reliable data are needed concerning
      the brace use. Questionnaires or clinical judgment usually estimates subjectively
      the compliance, which ranges from 20% to 90%. So far, only 1 study with 10
      patients has investigated the compliance by objective time-stamped logging in a
      daily life environment, showing an average brace use of 65%. METHODS: There were
      9 female patients (age 14.2 years, standard deviation 1.5) with adolescent
      idiopathic scoliosis who took part in the study. Their thoracolumbosacral
      orthoses (Cheneau braces OT-Kiel, Kiel, Germany) were equipped with a
      specifically developed discrete data logger to record temperature at the skin
      brace interface over a period of 5.4 weeks (standard deviation 3.1), at 2-minute
      date/time-stamped intervals. RESULTS: Brace use ranged from 4.2 to 22.4 hours per
      day (average 15.4 hours). Underlying the recommended bracing time of 23 hours,
      average compliance rate was 67.5% (range 19.0% to 97.1%). No patient reached a
      complete 23-hour bracing. Patients with poor compliance usually removed the brace
      during the daytime. The individual bracing pattern did not change over the course
      of an evaluation period, and the compliance can be estimated after 2 weeks.
      CONCLUSIONS: Long-term logging of temperature within a spinal orthosis is a
      reliable and simple way to measure objectively the compliance. Thus, comparison
      of full-time and part-time bracing is made possible on an objective basis.
      Furthermore, knowing the bracing pattern provides a better focus on other
      variables of spinal bracing, such as the force distribution within the brace.
      This knowledge may help to improve further the shape and effectiveness of
      bracing.

PMID- 16449909
TI  - Complications in spinal fusion for adolescent idiopathic scoliosis in the new
      millennium. A report of the Scoliosis Research Society Morbidity and Mortality
      Committee.
AB  - STUDY DESIGN: The Morbidity and Mortality database of the Scoliosis Research
      Society (SRS) was queried as to the incidence and type of complications as
      reported by its members for the treatment of adolescent idiopathic scoliosis
      (AIS) with spinal fusion and instrumentation procedures regarding surgical
      approach (anterior, posterior, or combined anterior-posterior) during a recent 3
      year period. OBJECTIVE: To evaluate the incidence of surgeon-reported
      complications in a large series of spinal fusions with instrumentation for a
      single spinal deformity diagnosis and age group regarding surgical approach.
      SUMMARY OF BACKGROUND DATA: The SRS has been collecting morbidity and mortality
      data from its members since its formation in 1965 with the intent of using these
      data to assess the complications and adverse outcomes (death and/or spinal cord
      injury) of surgical treatment for spinal deformity. Surgical approaches to the
      management of treatment of AIS have a measurable impact on efficacy of
      correction, levels fused, and operative morbidity. However, there is a lack of
      consensus on the choice of surgical approach for the treatment of spinal
      deformity. METHODS: Of the 58,197 surgical cases submitted by members of the SRS
      in the years 2001, 2002, and 2003, 10.9% were identified as having had anterior,
      posterior, or combined spinal fusion with instrumentation for the diagnosis of
      AIS, and comprised the study cohort. All reported complications were tabulated
      and totaled for each of the 3 types of procedures, and statistical analysis was
      conducted. RESULTS: Complications were reported in 5.7% of the 6334 patients in
      this series. Of the 1164 patients who underwent anterior fusion and
      instrumentation, 5.2% had complications, of the 4369 who underwent posterior
      instrumentation and fusion, 5.1% had complications, and of the 801 who underwent
      combined instrumentation and fusion, 10.2% had complications. There were 2
      patients (0.03%) who died of their complications. There was no statistical
      difference in overall complication rates between anterior and posterior
      procedures. However, the difference in complication rates between anterior or
      posterior procedures compared to combined procedures was highly significant (P <
      0.0001). The differences in neurologic complication rates between combined and
      anterior procedures, as well as combined and posterior procedures were also
      highly statistically significant (P < 0.0001), but not between anterior and
      posterior procedures. CONCLUSIONS: This study shows that complication rates are
      similar for anterior versus posterior approaches to AIS deformity correction.
      Combined anterior and posterior instrumentation and fusion has double the
      complication rate of either anterior or posterior instrumentation and fusion
      alone. Combined anterior and posterior instrumentation and fusion also has a
      significantly higher rate of neurologic complications than anterior or posterior
      instrumentation and fusion alone.

PMID- 16449910
TI  - Outcome at 10 years after treatment for adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: A total of 215 consecutive patients treated either by bracing or
      operation received a questionnaire after 9.7 years. OBJECTIVE: The aim of the
      present study was to elucidate the long-term outcome in a group of brace (BT) or
      surgical treated (ST) patients suffering AIS. SUMMARY OF BACKGROUND DATA: In
      adolescent idiopathic scoliosis (AIS), the options are BT or ST and, together
      with the disease itself, they may both be physically and psychologically
      demanding. METHODS: The main topics of a questionnaire were demographics, back
      pain, activities of daily living, and SF-36. RESULTS: A total of 181 replied. The
      mean age at follow-up was 26.0 years. The level of back or leg pain was
      relatively low, and the BT patients had more pain than their ST peers. We saw a
      generally high level of ADL and found no significant difference between BT and ST
      patients in the present study for any of the SF-36 variables. Compared with age
      matched controls, the SF-36 scores were lower in the AIS patients. Brace related
      questions revealed a significant impact of the disease and the treatment on the
      patients' lives. CONCLUSIONS: The patients had moderately reduced perceived
      health status and activities of daily living, and increased pain with the ST
      patients generally at a better level than the BT.

PMID- 16449911
TI  - Nonoperative treatment for adolescent idiopathic scoliosis: a 10- to 60-year
      follow-up with special reference to health-related quality of life.
AB  - STUDY DESIGN: Retrospective study on patients 10 to 60 years of age after
      nonoperative treatment for adolescent idiopathic scoliosis (AIS). OBJECTIVES: To
      investigate long-term outcome with regard to pain, disability, psychological
      disturbance, and health-related quality of life (HRQOL) in nonoperatively treated
      patients with AIS. SUMMARY OF BACKGROUND DATA: Only little is known on the long
      term quality of life and disability in patients nonoperatively treated for AIS. A
      detailed knowledge of the nonoperative treatment results is important when
      advising patients for surgery. METHODS: A total of 135 nonoperatively treated AIS
      patients with a minimum follow-up of 10 years were included in this
      investigation, 121 of whom responded to a questionnaire containing questions on
      pain, disability (Oswestry Disability Index [ODI], Hannover Functional Ability
      Questionnaire [HFAQ], psychological general well-being [PGWB], and health-related
      quality of life [WHOQOLBREF]). Eighty-one patients participated in a
      clinical/radiologic follow-up examination. Nonoperative treatment consisted of
      bracing (n = 60), physiotherapy (n = 59), and electrical stimulation (n = 2). The
      overall follow-up rate was 89.6%. The mean age at follow-up was 38.0 years
      (range, 20-73 years.). RESULTS: In general, patients achieved a satisfactory
      outcome 10 to 60 years (mean, 23 years) after nonoperative treatment with regard
      to pain, disability, and HRQOL. The average curve at first diagnosis measured
      29.5 degrees (range, 15 degrees -59 degrees ) for the thoracic spine, 21.3
      degrees (range, 15 degrees -28 degrees ) for the thoracolumbar spine, and 26.8
      degrees (10 degrees -44 degrees ) for the lumbar spine. Thirteen patients showed
      a substantial change in curve size (+/-10 degrees ) between first diagnosis and
      end of growth: 11 curves progressed more than 10 degrees showing an average
      increase of 19.0 degrees (range, 12 degrees -30 degrees ) and 2 patients
      presented with less severe curves at follow-up (-10 degrees and -13 degrees ).
      After end of growth, 7 patients showed a substantial average increase of 16.3
      degrees (range, 10 degrees -31 degrees ). Five of eight patients with thoracic
      curves greater than 80 degrees had restrictive pulmonary disease. Patients with
      curves greater than 45 degrees reported significantly higher pain levels than
      those with smaller curves. Patients only showed a minimal absolute disability
      (Oswestry and HFAQ), and no significant correlation was found between curve size
      and curve type, respectively. Compared with a healthy control group that was
      matched for age and gender, no significant differences were found in terms of
      HRQOL as assessed by the WHOQOLBREF questionnaire. No significant differences in
      pain, disability, or HRQOL were found between patients with and without brace
      treatment. CONCLUSIONS: Although pain, disability, HRQOL, and psychological
      general well-being are quite satisfactory on an absolute level, curve size was
      found to be a significant predictor for pain in a long-term follow-up.

PMID- 16449914
TI  - Our failure as surgeons to take enough interest in nonoperative care to be more
      secure in predicting success of the operative care.

PMID- 16449915
TI  - Fixation with poly-L-lactide screws in hip osteotomies.
AB  - The purpose of our study was to investigate the bone union rates and complication
      rates, including breakage of screws, infection, and osteolysis, in hip
      osteotomies using poly-L-lactic screws. We prospectively followed up 111 hips in
      100 patients using conventional radiography, in which 81 rotational acetabular
      osteotomies, 26 Chiari pelvic osteotomies, and four Sugioka's transtrochanteric
      osteotomies were performed. The mean age of the patients at the time of surgery
      was 34 years, and the mean followup was 5.4 years. Eighty-one osteotomized
      acetabula and 98 osteotomized greater trochanters were fixed using poly-L-lactic
      screws. These hips were compared with 64 hips in 58 patients using metallic
      screws. Bone union was achieved in 80 of the 81 acetabular osteotomies, except in
      one hip with postoperative deep infection. Proximal displacement of the greater
      trochanter because of poly-L-lactic screw breakage occurred in six (6%) hips.
      None of the metallic screws broke. Osteolysis occurred in one hip with a
      trochanteric osteotomy using poly-L-lactic screws. Poly-L-lactic screws are
      suitable to transfix the osteotomized acetabulum, but there is some risk of
      fracture when used to reattach an osteotomized greater trochanter. Complete bone
      ingrowth in the screw channels cannot be expected for several years after
      insertion. Osteolysis is a possible complication. LEVEL OF EVIDENCE: Therapeutic
      study, Level II (prospective comparative study). See the Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 16449916
TI  - Advantage of limb salvage over amputation for proximal lower extremity tumors.
AB  - Although function after lower extremity amputation and limb salvage has been
      compared, no study has assessed individual functional variables by surgical
      level. Our aim was to determine whether risks of long-term psychologic and
      physical limitations were associated with amputation or limb salvage at four
      levels: below-knee, above-knee, hip, and pelvis. We included 408 patients with
      sarcomas and postoperative followup of 2 years or greater who had completed a
      quality-of-life self-report questionnaire. The mean length of followup was 8.91
      +/- 5.15 years (range, 2-27 years). Relative risk analysis was done on 12
      dichotomous general health, psychologic, and physical function variables. At the
      below-knee level, outcomes were similar after both procedures. At the above-knee
      level, amputation was associated with increased risk of limp (RR = 1.6), walking
      aid use (RR = 2.1), anxiety (RR = 2.4), and inability to drive (RR = 3), and
      decreased risk of muscle weakness (RR = 0.57). At the hip and pelvic levels,
      outcomes were descriptively compared because of the small number of amputations.
      At these higher levels, limitations were more common after amputation. The
      difference in results between the below-knee and above-knee levels supports the
      importance of distinguishing surgical levels. Limb salvage offers a functional
      advantage at proximal tumor locations. LEVEL OF EVIDENCE: Therapeutic study,
      Level III (retrospective, comparative study). See the Guidelines for Authors for
      a complete description of levels of evidence.

PMID- 16449917
TI  - Muscle strength improves after abductor-sparing periacetabular osteotomy.
AB  - We measured muscle strength after curved periacetabular osteotomy, one form of
      abductor-sparing periacetabular osteotomy, and then investigated the factors
      influencing postoperative muscle strength recovery. Curved periacetabular
      osteotomy was performed for acetabular dysplasia on 24 hips in 22 patients. All
      patients were females, with a mean age of 34.4 years. We based the severity of
      hip disease on the Tonnis classification. Isokinetic muscle strengths of the hips
      were measured preoperatively and 6 months and 12 months postoperatively. At 12
      months postoperatively, the mean muscle strength (percentage difference to
      preoperative value) of the abductor was 42.2 Nm (129.6%), adductor 39.4 Nm
      (131.4%), flexor 48.4 Nm (121%), and extensor 45.8 Nm (130.5%), all of which
      exceeded the preoperative values. The 12-month postoperative muscle strength of
      patients with Grade 0 disease based on the Tonnis classification was greater in
      all directions than that of patients with Grades 1 and 2 disease. The
      preoperative stage was thought to be an essential factor in postoperative muscle
      strength recovery. LEVEL OF EVIDENCE: Prognostic study, Level II (lesser quality
      prospective study--eg, patients enrolled at different points in their disease or
      < 80% followup). See the Guidelines for Authors a complete description of levels
      of evidence.

PMID- 16449920
TI  - [Surgery for morbid obesity: necessary medical and surgical follow-up].

PMID- 16449921
TI  - [Bird flu, from where to where?].

PMID- 16449922
TI  - [Update on the human form of bird flu].

PMID- 16449923
TI  - [Clinical aspects and diagnosis of pleural fibromas].
AB  - Pleural fibromas are rare malignant or benign tumors requiring pathology study
      for certain diagnosis. From January 1985 to January 2001, 7 patients underwent
      surgery in our unit for pleural fibroma: 4 females and 3 males, mean age 60
      years. The inaugural symptoms were chest pain (3 patients), dyspnea (2 patients),
      joint pain in a patient with Pierre-Marie pneumonic hypertrophic osteo
      arthropathy, and acute hypoglycemia. Radiological investigations were decisive in
      orienting the diagnosis (chest X-ray, ultrasound, computed tomography and MRI).
      Surgical resection and pathological study of the surgical specimen is required to
      confirm the diagnosis. Patients should be carefully followed due to the risk of
      malignant recurrence.

PMID- 16449924
TI  - [Results of an ambulatory respiratory rehabilitation program: observations in 100
      COPD patients].
AB  - INTRODUCTION: Respiratory rehabilitation is a multidisciplinary approach enabling
      personalized management adapted for each patient's handicap. METHOD: Our
      ambulatory program includes twenty sessions per week (four half-days/week) for
      respiratory training at the ventilatory threshold, respiratory physical therapy,
      and health education. One hundred COPD patients participated in this
      retrospective study: mean age 62.1 +/- 9.6 years; FEV1: 1.51 +/- 0.66 (53 +/- 22%
      of theoretical). RESULTS: At the ventilatory threshold, there was a significant
      9% gain in oxygen uptake and a 31% gain in power. At maximal exercise, there was
      a 6% improvement in oxygen uptake, 21% gain in power, and 7% gain in tidal volume
      (p<0.05). Walking distance improved 15% (+ 61 m). Quality of life was also
      improved significantly, with loss of 8 points on the Saint-George's Hospital
      respiratory questionnaire. CONCLUSION: This study demonstrates the beneficial
      effect of respiratory rehabilitation in terms of improved tolerance to exercise
      and improved quality of life for COPD patients.

PMID- 16449925
TI  - [Pseudotumoral presentation of American pulmonary histioplasmosis].
AB  - In France, American pulmonary histoplasmosis is an imported deep mycosis, caused
      by inhalation of Histoplasma capsulatum. Clinical and radiological features of
      this exotic disease are multiple, simulating tuberculosis or cancer. We report
      two cases of American histoplasmosis with pseudo-tumoral form, in immunocompetent
      subjects working in Venezuela, with a multinodular pulmonary presentation.

PMID- 16449926
TI  - [Chylothorax of cirrhotic origin: a case report].
AB  - Chylothorax and chylous ascites are an accumulation of fluid containing a large
      proportion of triglycerides. The presence of these two effusions simultaneously
      is rare. A case of a patient with a known history of cirrhosis, hospitalized for
      an ascetic decompensation with left pleural effusion is herein presented. The
      woman was diagnosed as presenting both chylous ascites and chylothorax. Both
      fluids are transudate type fluids. After evacuation of the fluids and
      implementation of an adapted treatment neither effusion reappeared. The patient
      has been followed for the past year and has not shown any signs of relapse.
      Chylothorax, in cirrhotic patients is due to trans-diaphragmatic passage of fluid
      originating from the chylous ascites. Both extravasations have the same
      biological characteristics.

PMID- 16449927
TI  - [Left strangulated diaphragmatic hernia: an unusual complication of gastric
      bypass].
AB  - The appearance of left strangulated diaphragmatic hernia doesn't seem to have
      been described in the past as a progressive complication after gastric bypass
      surgery. The authors describe the case of a 54 year old patient suffering from a
      strangulated gastric hernia pushing through a diaphragm defect located next to
      the gastric band. The gastric band had been placed two years previously in this
      patient suffering from morbid obesity. Strangulation of the hernia resulted in
      the sphacelation of the entire stomach fundus. Therefore a partial gastrectomy
      and removal of the band was necessary. Recovery from procedure was without
      complications. The past history of a major spinal trauma in this patient, could
      have led to a discussion regarding the etiology of this hernia, however the delay
      between the two events (28 years) makes this unlikely. It seems, therefore, that
      the placement of a gastric band was the responsible factor. The authors emphasize
      the importance of pre-procedure pulmonary X-ray, prior to any general anesthesia,
      as well as a post procedure cliche following any intervention that might have
      lead to diaphragmatic lesion.

PMID- 16449928
TI  - [Huge benign lung tumor in a female smoker].
AB  - Pulmonary sclerosing hemangioma is a rare, slow-growing, benign tumor. Its
      potential for progression and its histiogenesis remains controversial. CASE
      REPORT: A routine chest X-ray revealed a right abdominal mass in 41-year-old
      woman. Search for a cause was negative. The patient underwent posterolateral
      thoracotomy for tumorectomy. Intraoperative pathology analysis revealed the
      benign nature of the tumor. No complication was observed postoperatively. The
      final pathological conclusion was sclerosing hemangioma of the lung. Pulmonary
      sclerosing hemangioma is a parenchymal tumor of the lung. The latest
      immunohistochemical studies of this lesion suggest a pneumocyte origin. Prognosis
      is good, but extension to lymph nodes may occur. Surgery is always required for
      cure, and must be associated with lymph node dissection for large tumors.

PMID- 16449929
TI  - [Chronic atrophic polychondritis. A case report].
AB  - Chronic atrophic polychondritis is a rare systemic disease characterized by
      recurring inflammation of cartilage of the ear, nose, larynx and of the
      tracheobronchial tree. Nowadays, it is considered to be an autoimmune disease.
      The case of a 25-year-old female patient hospitalized in our department for
      treatment of a dyspnea is herein presented. ORL laryngoscopic examination
      revealed a small sized larynx with a pronounced narrowing of its lumen and very
      "floppy" cartilage. Bronchoscopic findings were a circumferential stenosis along
      the entire trachea and the right major bronchi. Results from biopsies performed
      on the trachea and thyroid cartilage were in favor of chronic atrophic
      polychondritis. The course of the disease was characterized by an aggravation of
      the dyspnea with episodes of asphyxia resulting in a tracheotomy. The tracheotomy
      has not been closed to this day, due to the underlined disease of the patient.

PMID- 16449931
TI  - [Pharmaceutical practices in oncology: from hospital to dispensary.
      Introduction].

PMID- 16449930
TI  - [Large bilateral lung opacities].
AB  - We report the case of a 42-year-old woman operated for neurofibroma of the scalp
      on two occasions who consulted for bilateral chest pain which reveated two
      voluminous bilateral pulmonary masses. Biopsy of one of these masses was in favor
      of secondary or primary leiomyosarcoma. The association of Von Recklinghausen's
      disease and soft tissue sarcoma is rare: most often neurofibroma which
      degenerates is observed. Other types of sarcoma, like leiomyosarcoma, have been
      described.

PMID- 16449933
TI  - [Preparation of antineoplastic agents].
AB  - In the last fifteen years, the preparation of antineoplastic agents has tended to
      be centralized in the hospital pharmacy for two main reasons: to enable better
      protection for the staff, to enable better safety for the patient. The
      consequences of this organization have led to standardization of techniques,
      implementation of a quality system and also a better use of antineoplastic
      agents. After protocols have been standardized by the physician and validated by
      the pharmacist, four main steps are necessary: phamaceutical validation of the
      prescription, preparation of IV admixtures according to a production file,
      control of the final product, dispatching of the preparation to the patient.
      Computer-controlled processes guarantee the safety of these different steps. The
      centralized preparations are made either with a vertical laminar flow hood or
      with an isolator. With the implementation of the National Cancer Plan,
      antineoplastic agents for patients on home treatments will also be prepared in
      centralized hospital pharmacies.

PMID- 16449934
TI  - [Management of cancer pain in children].
AB  - Pain and cancer cannot be dissociated. A particular feature observed in children
      is that the child exhibits a certain psychomotor atony with increasing pain. The
      child complains less and less, making it difficult to recognize the degree of
      suffering and provide adequate relief. The most painful events for the child are
      iatrogenic: local care, puncture, injection, infusion, sample taking. The
      healthcare team must limit such events to the strict minimum.

PMID- 16449935
TI  - [New drug formulations for cancer therapy].
AB  - Despite recent emergence of novel therapeutic agents the major progress achieved
      in cancer treatments results from conventional drugs used for cytotoxic or
      hormone therapy. Over the past 20 years, a more rational and more pharmacological
      based approach to chemotherapy has led to major successes. One of the most
      promising avenues of research is to improve the pharmacokinetic properties of
      well-known anticancer drugs (bioavailability, distribution, targeting, drug
      carriers) by modifications of their formulations (new drug delivery systems). As
      an example, new pharmaceutical forms of analogs of LH-RH, (microparticles or
      implants) permitting sustained release of the drug for months, are now largely
      used in the routine chemotherapy for prostate cancers. Improvement of the oral
      bioavailabilty of drugs previously administered only by the parenteral route is
      simplifying treatment protocols. Parenteral delivery of doxorubicine entrapped in
      liposomes (pegylated liposomes) decreases the cardiotoxicity and increases the
      half-live of this drug widely used in the treatment of breast carcinomas.
      Molecular targeting using immunocarriers such as immunoliposomes is also a very
      strong field of research.

PMID- 16449936
TI  - [Characteristics of clinical trials in oncology: pharmacist's implication].
AB  - French hospital pharmacists have been officially involved in the organization of
      clinical trials since 1988. New responsibilities included reception of clinical
      treatment units and nominative dispensation of these drugs. For quality
      assurance, they organized all the procedures to secure drugs utilization
      according to good clinical practices and ICH guidelines. The pharmacists can be
      participate in ethical counselling and training in methodology. For oncology
      trials, only a few pharmacies are involved because clinical trials for evaluation
      of cytotoxic drugs have been regulated by very strict standardized procedures
      since 1960 in accordance with international rules. Using these rules, Phase I
      studies determine the useful dose for human administration with tolerable
      toxicities. Phase II studies determine the efficacy in specific cancer
      localizations. Good response in a particular indication is usually followed by
      drug approval for Phase III. New clinical and biological end points are arising
      especially for new non-cytotoxic therapeutic agents. This activity is at the
      present time limited to inpatient treatments, but with the growing development of
      outpatient care networks, dispensary pharmacists will come to be more involved in
      the necessary research and development of new anticancer agents.

PMID- 16449939
TI  - Paracelsus: a reevaluation.
AB  - After reviewing the notions of Paracelsus concerning medicine and his ideas about
      knowledge and science, the author discusses his contributions to medicine and
      science. He also discusses the reasons for his popularity. The general conclusion
      is that Paracelsian medicine represented a return to the supernaturalistic
      healing practices of the past.

PMID- 16449938
TI  - [Quality control of hospital preparations: results concerning capsules production
      in a child hospital].
AB  - In France, lack of paediatric drugs leads pharmacies to produce many hospital
      preparations in order to meet prescribers'needs. To ensure the quality of these
      preparations, the pharmacy department of the Armand Trousseau Child Hospital set
      up a quality control system of its capsules. It integrates both European
      Pharmacopeia's requirements (Mass and Content uniformity test) and more strict
      internal quality specifications. They include exactitude of the average content
      compared to the awaited content, coefficient of variation of the contents and,
      "modified" content uniformity test. These criteria and the percentage of
      nonconformity are used as indicators to assure quality follow-up of the
      preparations. We reviewed quality control records for five hospital preparations
      produced over the last three years. We highlighted that lower dosage showed a
      higher percentage of nonconformity compared to higher dosage. Type of active
      ingredients was a key factors too (1,0% and 14.8% of non conform batches for
      ursodesoxycholic acid and for morphine hydrochloride respectively). Analysis
      showed that the essential character of content test because mass test is not
      predictive of the conformity of the batch. Content test was the main criterion to
      judge batches conformity. Thus, it will be generalized to all our preparations.
      These study results helped us to implement new procedures to assure an ongoing
      improvement of our practices of preparation.

PMID- 16449940
TI  - [Research of 99mTcO4- and 99mTcO2- in injectable solutions of 99mTc-HMDP by
      inverse phase HPTLC].
AB  - Bone scintigraphy allows the diagnostic of many pathologies related to bone
      through the intravenous administration of a phosphonate bone marker complexed to
      99 metastable technetium (99mTc). The instability of these injectable solutions
      on contact with air can lead to a mixture of pertechnetate VII (99mTcO4-) and
      technetium IV (99mTcO2-, xH2O), technetium IV being the only derivative to fix
      bone. A qualitative control of the purity of these solutions proved to be
      consequently important before administration. We report here the perfecting of a
      new chromatographic test based on reverse phase high performance thin layer
      chromatography (HPTLC). This test, simple, rapid and reproductive allows without
      ambiguity the detection of 99mTcO4-(VII) and 99mTcO2-(IV), xH2O in
      hydroxymethylene diphosphonate (HMDP) injectable solutions ready to use.

PMID- 16449941
TI  - Pilot study of the G-protein beta3 subunit gene (C825T) polymorphism and clinical
      response to olanzapine or olanzapine-related weight gain in persons with
      schizophrenia.
AB  - BACKGROUND: Despite advances in schizophrenia treatment, nearly 30% of patients
      do not respond to atypical antipsychotic agents, such as olanzapine. Furthermore,
      30-60% of patients will gain significant weight during the course of olanzapine
      therapy. Little research has been done to investigate the relationship between
      antipsychotic treatment outcomes and genetic variability in second messengers
      coupled to serotonin (5HT) receptors. The purpose of this investigation was
      examine associations between the second messenger G-Protein Beta3 Subunit Gene
      (GNB3) C825T polymorphism and olanzapine response and weight gain treatment.
      MATERIAL/METHODS: We conducted a pharmacogenetic association study to examine
      GNB3 genotypes in relation to olanzapine clinical response (as measured by the
      Brief Psychiatric Rating Scale or Scale for the Assessment of Negative Symptoms)
      or weight gain. Subjects included forty-two individuals meeting DSM-IV criteria
      for schizophrenia that started olanzapine, were titrated to a fixed dose for 6
      weeks, and subsequently genotyped for this investigation. RESULTS: No
      statistically significant associations existed between our outcome variables and
      GNB3 genotypes. However we did observe trends suggesting a potential relationship
      between the TT genotype, response, and weight gain that warrant further
      investigation. CONCLUSIONS: Preliminary results showed no statistical
      relationship between the C825T polymorphism and olanzapine response or weight
      gain. Numerical differences in outcome measures between the TT vs. CT/CC genotype
      groups indicate that G-protein second messenger systems variability coupled to
      primary targets of atypical antipsychotics may relate to clinical outcomes in
      persons with schizophrenia and that future research in this area is warranted.

PMID- 16449942
TI  - Matrix metalloproteinase inhibitor (ONO-4817) attenuates ischemia-reperfusion
      injury in rat lung.
AB  - BACKGROUND: Ischemia-reperfusion injury of the lungs seems to be initiated by the
      activation of alveolar macrophages, and mediated by matrix metalloproteinases
      (MMP)s, although their roles have not been fully elucidated. Therefore, we used a
      novel MMP inhibitor (ONO-4817) with high affinities for MMP-2 and MMP-9 to
      investigate the roles of MMPs in reperfusion injury of the lungs.
      MATERIAL/METHODS: After 18 h of cold ischemia, isolated rat lungs were ventilated
      and reperfused. Lungs without ischemia served as controls. Lungs were reperfused
      with fresh blood with or without the MMP inhibitor for 120 min at 37 degrees C.
      RESULTS: The oxygenation capacity of lungs after ischemia deteriorated
      progressively during 120 min of reperfusion, but was preserved by the MMP
      inhibitor (p<0.05). The histopathology of the lungs after ischemia-reperfusion
      showed interstitial edema accompanied by neutrophil migration, and the number of
      neutrophils, but not macrophages, in the broncho-alveolar lavage increased to
      more than two-fold the value in control lungs without ischemia (p<0.01). These
      changes were attenuated by the MMP inhibitor (p<0.01). Similarly, an increase in
      the tissue malondialdehyde level in lungs after ischemia-reperfusion was
      ameliorated by the MMP inhibitor (p<0.01). The expressions of CD11c and CD31
      adhesion molecules in extracted alveolar macrophages increased in lungs after
      ischemia-reperfusion compared with control lungs without ischemia, and the MMP
      inhibitor had no obvious effect. CONCLUSIONS: Our data show that ONO-4817
      prevented neutrophil migration into the interstitial space and alveolus in the
      lungs, and reduced the production of oxygen free radicals, suggesting that this
      is an important mechanism in reperfusion injury.

PMID- 16449943
TI  - Bifenthrin inhibits neurite outgrowth in differentiating PC12 cells.
AB  - BACKGROUND: Bifenthrin is a third generation member of the synthetic pyrethroid
      family of insecticides. As a new pesticide within a relatively new class of
      pesticides, bifenthrin is considered relatively safe. Here, we used the PC12
      neuronal cell line to examine the effect of bifenthrin on the formation of
      neurites and the potential developmental neurotoxicity of this pesticide.
      MATERIAL/METHODS: PC12 cells were exposed to varying concentrations of technical
      grade bifenthrin or Ortho Home Defense. Cell viability was determined using the
      AlmarBlue Toxicity Assay. Nontoxic concentrations of these chemicals were
      concomitantly with nerve growth factor and neurite outgrowth was assessed.
      RESULTS: Ortho Home Defense preparation reduced PC12 cell viability by
      approximately 50% and 70% at dilutions that correlate to bifenthrin
      concentrations of 10(-5) M and 10(-4) M, respectively. In contrast, technical
      grade bifenthrin, was not toxic to PC12 cells at 10(-3) M, which was the highest
      concentration tested that was soluble. At "nontoxic" concentrations of 10(-7) M
      and 10(-6) M, the Ortho Home Defense inhibited nerve growth factor-mediated
      neurite outgrowth by 30% and 55% respectively. Furthermore the nontoxic
      concentrations of technical grade bifenthrin of 10(-6) M and 10(-3) M inhibited
      neurite outgrowth by approximately 35% and 75% respectively. CONCLUSIONS: These
      data suggest that the toxicity of the Ortho Home Defense preparation was due to
      the "inert" additives in the preparation and not the bifenthrin itself. Further,
      these data suggest that, even in the absence of overt toxicity, bifenthrin may
      have deleterious effects to developing nervous system.

PMID- 16449944
TI  - Activation of genes inducing cell-cycle arrest and of increased DNA repair in the
      hearts of rats with early streptozotocin-induced diabetes mellitus.
AB  - BACKGROUND: Oxidative stress was proposed as a critical factor in diabetic
      complications. The etiology of cell degeneration in diabetes mellitus (DM)
      induced cardiomyopathy is unclear. The transition between apoptotic degeneration
      and cell proliferation under stress conditions is regulated at cell-cycle
      checkpoints. This study was aimed at elucidating the role of a potent cellular
      stress-response system of the p53-dependent checkpoint genes, i.e. P21WAF1/CIP1
      and 14-3-3 sigma, in the heart in diabetes. MATERIAL/METHODS: Target gene
      expression levels were analyzed ex vivo in cardiomyocytes of streptozotocin
      induced rats by Western blots and two-dimensional immunoblots. The levels of DNA
      damage/repair in diabetic cardiomyocytes were evaluated by "comet assay" and
      compared with a control group. RESULTS: Whereas no detectable expression of 14-3
      3 sigma and only traces of both p53 and p21WAF1/CIP1 were found in cardiomyocytes
      of the controls, high expression rates of all three genes were observed in the DM
      group. Individual levels of DNA breakage were significantly lower in diabetic
      than in non-diabetic cardiomyocytes. CONCLUSIONS: We propose a dual role for cell
      cycle regulation under diabetic conditions: the expressions of both p21WAF1/CIP1
      and 14-3-3 sigma genes, activated via p53 function, trigger cell-cycle arrest and
      DNA repair, preventing replication of mutated DNA and increasing stress
      resistance of heart tissue at least in early diabetes. However, the double cell
      cycle arrest ultimately inhibits the replication of cells, which consequently
      accumulate in the G1 and G2 phases; this could lead to retarded proliferative
      activity and tissue degeneration in diabetic myocardium in later diabetes.

PMID- 16449945
TI  - Detection of nitric oxide in culture media and studies on nitric oxide formation
      by marine microalgae.
AB  - BACKGROUND: Multiple functions of nitric oxide (NO) in organisms and its special
      function and role in the atmosphere were investigated. In this study, marine
      microalga culture-medium NO concentrations were detected and studied in order to
      find the laws governing NO release by marine microalgae and relevant material was
      collected for discussion on the production mechanisms. MATERIAL/METHODS: NO
      concentrations in culture media of the marine microalgae Platymonas
      subcordiformis, Skeletonema costatum, and Gymnodinium sp. were detected and other
      media parameters, such as nutrients concentrations, Chl-a, alga cell density, and
      pH, were also measured concurrently. RESULTS: The NO concentrations in culture
      media of the marine microalgae Platymonas subcordiformis, Skeletonema costatum,
      and Gymnodinium sp. were detected and found to be about 10(-8)-10(-9) mol/l. The
      relationships between NO and nutrients and NO and pH were discussed. It was found
      that "NO" could serve as the message factor of microalga growth status.
      Experiments showed that factors affecting alga growth, such as trace elements,
      light, temperature, and salinity, all affected the culture-medium NO
      concentration. At the same time, an environmental stimulus could give rise to
      sudden NO peaks, with NO being a signal molecule of marine microalga stress
      response. CONCLUSIONS: These results indicated that low concentrations of NO were
      produced by marine phytoplankton (microalgae) under the condition of normal
      growth. NO is a message factor of microalga growth and is also a signal molecule
      of stress response.

PMID- 16449946
TI  - Exercise increases soluble vascular endothelial growth factor receptor-1 (sFlt-1)
      in circulation of healthy volunteers.
AB  - BACKGROUND: Physical inactivity increases the risk of cancer and atherosclerosis;
      the impaired regulation of angiogenesis is often associated with the development
      of these diseases. We hypothesize that exercise increases circulating sFlt-1, an
      endogenous VEGF inhibitor, which may functionally decrease plasma levels of free
      VEGF. MATERIAL/METHODS: 5 healthy male adults were assigned to a treadmill
      exercise study. The peak speed and the time spent at peak speed on the treadmill
      were 4.8+/-1.0 miles/h and 6.8+/-2.6 minutes, respectively. Plasma levels of sFlt
      1 and VEGF were determined using ELISA (R&D Systems). RESULTS: Basal plasma
      levels of sFlt-1 (before exercise) were 48.8+/-9.0 pg/ml. Plasma levels of sFlt-1
      increased to 72.9+/-14.6 pg/ml at 0.5 h after exercise, compared to the basal
      levels (49% higher, P=0.0048). The plasma levels then returned to 47.5+/-14.3 and
      43.3+/-10.2 pg/ml, at 2 and 6 h after exercise, respectively. There was a
      significant positive correlation between % increase in plasma levels of sFlt-1
      and total peak oxygen consumption during exercise (R2=0.8244; P<0.01). Basal
      plasma levels of unbound VEGF were 37.3+/-7.7 pg/ml, then decreased to 28.2+/
      6.3, 17.5+/-2.5, and 26.6+/-6.4 pg/ml, at 0.5, 2, and 6 h, respectively, after
      exercise. There was a significant increase in basal plasma levels of sFlt-1 after
      repeated exercise for 2 weeks. CONCLUSIONS: We have demonstrated that circulating
      sFlt-1 is significantly increased by exercise in healthy volunteers, which is
      functionally associated with a transient decrease in circulating free VEGF. This
      data may provide new insight into the molecular links between physical inactivity
      and risk of cancer and atherosclerosis.

PMID- 16449947
TI  - Health problems among six-week old Pacific infants living in New Zealand.
AB  - BACKGROUND: The purpose of this paper is to describe maternal reports of various
      health problems experienced by their Pacific infants in the first six weeks of
      their lives and to examine the infant, maternal and socio-demographic factors
      associated with infant health problems. MATERIAL/METHODS: The data were gathered
      as part of the Pacific Islands Families: First Two Years of Life (PIF) Study in
      which mothers in the cohort (n=1376) were interviewed about the health problems
      experienced by their infants (n=1398) in the first six weeks of life. RESULTS:
      Fifty-five percent of mothers reported that their infant had experienced minor
      health problems, and 15.6% reported moderate to severe infant health problems.
      Most mothers (98%) reported that they had a regular family doctor or health
      clinic to go to if their infant had a health problem. We found no meaningful
      associations between infant, maternal, or socio-demograhic variables and general
      infant health problems, possibly because of the wide range of infant illnesses
      reported. Since 43% of the infant health problems reported were related to
      breathing difficulties we carried out univariate and multivariate analyses on
      this specific health problem. Factors significantly associated (p<0.05) with
      infant breathing problems were maternal cigarette smoking during the last
      trimester, cold housing, and residing in New Zealand for over 10 years.
      CONCLUSIONS: The high rate of infant health problems, in particular infant
      breathing problems, among Pacific infants in this cohort and the significant
      links with modifiable factors warrant priority action by housing and health
      agencies to minimise the consequences of these risk factors.

PMID- 16449948
TI  - Validity of plasma fibrinogen, D-dimer, and the von Willebrand factor as markers
      of cardiovascular morbidity in patients on chronic hemodialysis.
AB  - BACKGROUND: Among the non-classic cardiovascular disease risk factors in end
      stage renal disease patients on chronic hemodialysis (HD), plasma fibrinogen, D
      dimer, and von Willebrand factor (vWf) levels are potential markers of
      cardiovascular morbidity. We designed this case-control study to investigate
      their validity and any differences between them. MATERIAL/METHODS: Twenty-five HD
      patients (18 males, mean age: 63, range: 52-69 years) comprised the group with
      prevalent cardiovascular disease (CVD) and 50 HD patients (35 males, mean age:
      62, range: 40-77 years) with non-evident cardiovascular disease history
      constituted the second study group. Twenty-five healthy non-smoking volunteers
      served as controls for comparison with the study groups. RESULTS: Patients with
      CVD had significantly higher concentrations of plasma fibrinogen, D-dimer, and
      vWf than patients without incident CVD. All three parameters correlated
      positively with cardiovascular morbidity, i.e. fibrinogen (r=0.378, P<0.001),
      logDD (r=0.70, P<0.001), vWf (r=0.214, P<0.001), and logCRP (r=0.704, P<0.001).
      Among them, D-dimer exhibited the characteristics most coherent with CVD. The age
      and sex-adjusted odds ratio (OR) of D-dimer for the presence of CVD was 2.0,
      which did not change appreciably when adjustments for several pathophysiological
      clusters of variables were made, except for a marginal reduction in OR following
      adjustment for markers of inflammation. CONCLUSIONS: Among the coagulation
      molecules studied, plasma D-dimer levels exhibited the characteristics most
      coherent with associated CVD and were found to be strongly and independently
      associated with the prevalence of CVD in HD patients.

PMID- 16449949
TI  - Establishing melanocyte cultures in a serum-free system for transplantation in
      vitiligo patients.
AB  - BACKGROUND: The aim of the study was to establish melanocyte cultures obtained
      from the epidermis of vitiligo patients for future treatment and to estimate the
      influence of selected factors on the formation of suction blisters and the
      results of culture. MATERIAL/METHODS: Twenty patients with generalized vitiligo
      were qualified to the study. The melanocyte donor site was the arm or forearm
      where, using an electric vacuum suction machine and a plastic plate, suction
      blisters were formed. The removed roofs of the blisters were used as a melanocyte
      source for culture establishment. After an enzymatic bath, the cell suspension
      was transferred to culture flasks containing melanocyte growth medium (MGM M2).
      The melanocytes in culture were identified by immunocytochemistry. RESULTS:
      Suction blisters were formed in all patients. No melanocyte cultures were
      established from patients whose blisters appeared over a period 58 minutes. In
      addition, a suitable quantity of melanocytes was not obtained for eight other
      patients (with skin phototype II and/or without previous PUVA therapy).
      CONCLUSIONS: The epidermis of the arm and forearm is a good donor site for the
      establishment of melanocyte cultures. The effectiveness of culture depends mainly
      on the time of the formation of suction blisters, the phototype of the skin, and
      previous PUVA therapy.

PMID- 16449950
TI  - Sexual dysfunction after curative radical resection of rectal cancer in men: the
      role of extended systematic lymph-node dissection.
AB  - BACKGROUND: This study was designed to determine the incidence and patterns of
      sexual dysfunction after curative radical resections (CRR) with or without
      extended systematic lymph-node dissection (ESLND) for rectal cancer
      Material/Methods: A total of 91 patients with rectal cancer were reviewed with
      respect to surgical procedures and postoperative sexual functions using the
      International Index of Erectile Function (IIEF), a 15-item self-administered
      questionnaire. CCR (abdomino-perineal resections or sphincter-saving anterior
      resections) was performed in 78 patients (Group I) and ESLND plus CRR in 13
      patients (Group II), and sexual functions were also evaluated in the colostomy
      and non-colostomy subgroups. RESULTS: In the postoperative period, the five
      domains of IIEF scoring decreased significantly from the preoperative scores in
      both groups (p<0.05), but the postoperative decreases were not significant
      between groups I and II (p>0.05). Having a permanent colostomy decreases IIEF
      scores in all colostomized patients. CONCLUSIONS: CRR and CRR+ESLND both decrease
      sexual function and lymph-node dissection is not considered to have any additive
      effect on this decrease. In addition to standard surgery, anxiety about having a
      malignant disease and permanent colostomy may play an important role in male
      sexual dysfunction.

PMID- 16449951
TI  - Risk factors of cardiovascular disease in GH-deficient adults with
      hypopituitarism: a preliminary report.
AB  - BACKGROUND: We estimated the influence of GH deficiency (GHD) in adults on chosen
      risk factors of cardiovascular disease and bone density. MATERIAL/METHODS: Fifty
      four adults (mean age: 50.4 years) with hypopituitarism were studied. We measured
      blood pressure, body mass index, waist-to-hip ratio, total body fat, and bone
      mineral density and the serum levels of lipids, glucose, insulin, pituitary
      hormones, estradiol, testosterone, and thyroxine, and the excretion of free
      cortisol in 24-h urine. GHD was confirmed with the insulin intravenous test (IIT)
      with a GH response to IIT of <3 microg/ml. The control group consisted of 73
      healthy adults. RESULTS: Increased levels of LDL-cholesterol and triglycerides
      and decreased levels of HDL-cholesterol in the GHD group were observed. Fasting
      serum glucose and insulin levels were significantly higher in the GHD group than
      in controls. Significant differences in the QUICKI and FIRI indexes were
      observed. Twenty-three percent of the hypopituitary patients were hypertensive
      and 65% were obese. The percentage of total body fat was significantly higher in
      the studied group than in controls. Thirty-seven percent of the GHD patients were
      osteoporotic and 23% were osteopenic. CONCLUSIONS: An atherogenic lipid profile,
      insulin resistance, obesity, and increased body and trunk fat in GHD adults may
      cause the higher risk of cardiovascular disease in these patients. GHD adults
      should receive human recombinant GH along with conventional replacement therapy.
      This may be a useful method in protecting against early onset of atherosclerosis,
      metabolic disturbances, and osteoporosis, especially in young patients.

PMID- 16449952
TI  - Microbiological surveillance in the intensive care unit: a tertiary hospital
      experience.
AB  - BACKGROUND: Hospital infections are important because of increased risk of
      mortality and morbidity and their economic burden and are most commonly seen in
      intensive care units (ICUs). We aimed to document the characteristics of patients
      at an ICU, obtain bacteriologic samples, and determine the distribution of the
      isolated microorganisms. MATERIAL/METHODS: The study was conducted in the ICU of
      an anesthesiology department with 16 beds. The characteristics of 154 patients
      treated there over a one-year period were documented. The distribution of
      bacteriologic samples and isolated microorganisms and susceptibilities were
      investigated. The emerging hospital infections were determined using surveillance
      methods that were based on clinical and laboratory data. RESULTS: Intoxication
      was the most common cause of hospitalization, followed by respiratory
      insufficiency due to severe pneumonia and/or chronic obstructive respiratory
      disease, then trauma, postoperative conditions, and cerebrovascular problems. The
      mean number of culture studies per patient was 5.36+/-3.27. Cultures were most
      commonly obtained from patients with respiratory insufficiency and trauma.
      According to clinical specimens, the most commonly isolated microorganisms were
      E. Coli (37.2%) in urine, S. Aureus (50.0%) in blood, P. aeruginosa (25.7%) in
      tracheal aspirates, and Acinetobacter spp. (37.5%) in wounds. Considering all
      specimens, MRSA (22.0%) was the most common microorganism. CONCLUSIONS: Hospital
      infections pose an serious problem in an ICU setting. Surveillance studies
      comprise the basis for treatment of ICU infections. A multidisciplinary approach
      is required for a better quality of care and the achievement of therapy.

PMID- 16449953
TI  - Primary hyperparathyroidism: a review of 177 cases.
AB  - BACKGROUND: We designed a comprehensive study to explore different aspects of
      primary hyperparathyroidism in a series of Iranian patients. Our study aimed to
      elucidate the demographic, pathologic, biochemical, and surgical findings of
      these patients. MATERIAL/METHODS: In a retrospective study from 1981 to 2003, we
      reviewed records of 177 patients operated on with the diagnosis of primary
      hyperparathyroidism in Shariati Hospital. Patients with secondary or tertiary
      hyperparathyroidism and those being re-operated were excluded. RESULTS: 88.1% of
      the lesions were adenoma, 9.6% hyperplasia, and 1 case proved to be carcinoma. In
      1.7% of patients, no pathologic gland(s) were found. The majority of patients
      were female (female-to-male ratio: 5.5) and their mean age was 41.9+/-13.6 years.
      Most of the patients (77.6%) had mild hypercalcemia, and the mean calcium level
      was 11.2+/-0.8 mg/dl prior to surgery. Patients with hyperplasia had lower
      calcium levels than patients with adenoma 24 hours post-operation, with mean
      calcium levels of 8.1+/-1.2 mg/dl versus 9.03+/-1.2 mg/dl, respectively (p=0.02).
      Mean weight of adenomas was 4.1 gram (range 0.8-25 g). Adenomas were mostly (74%)
      located in lower parathyroid glands and 6.3% of them were ectopic. CONCLUSIONS:
      Primary hyperparathyroidism should be expected at younger ages in Iran.
      Parathyroid hyperplasia in a patient should alert the surgeon of the higher risk
      of postoperative hypocalcemia.

PMID- 16449954
TI  - Effects of dopamine infusion on forearm blood flow in critical patients.
AB  - BACKGROUND: In critical care, dopamine is administered by infusion at low doses
      (<or=3 microg/kg/min) or at high doses (>or=5 microg/kg/min) for assessment of
      hemodynamics. The present study was conducted to explore the effects of dopamine
      infusion on the vast microvascular network of skeletal muscle in the early phases
      of sepsis. MATERIAL/METHODS: An observational study was performed which included
      twelve critically ill patients. Patients' response to dopamine infusion (3
      microg/kg/min) was studied within 24 hours from admission to the ICU. The forearm
      blood flow (FBF) and vascular resistance (FVR) were measured by near-infrared
      spectroscopy (NIRS). RESULTS: Dopamine did not ameliorate forearm regional
      oxygenation. The infusion of dopamine caused an increase in MAP, while FBF
      decreased with the resistance increase (p>0.05). CONCLUSIONS: NIRS was suitable
      to measure bedside the vascular resistance and to test the effects of low doses
      of dopamine on forearm blood flow. A dopamine infusion of 3.0 microg/kg/min
      caused a reduction in forearm blood flow and an increase in vascular resistance
      in our patients.

PMID- 16449955
TI  - Risk of blood splashes to masks and goggles during cesarean section.
AB  - INTRODUCTION: The study arose out of concern about the transmission of infectious
      diseases through mucocutaneous contact with blood and body fluids. The purpose
      was to identify the risk of blood splashes to masks and goggles during cesarean
      section. MATERIAL/METHODS: The prospective study spanned 6 months between January
      and June 1998 to determine the incidence of blood splashes to the masks and
      goggles of surgeons, assistants, and scrub nurses. All the doctors and scrub
      nurses who participated in surgery were requested to wear masks and goggles for
      all the cesarean section cases during the study period. At the end of surgery,
      the surgeon examined all the masks and goggles for obvious blood splashes and
      documented these in a data sheet. RESULTS: There were 144 cases of cesarean
      section performed during the period, of which 13.2% (19) were elective and 86.8%
      (125) were emergencies. 74.3% (107) of the patients registered for antenatal care
      and delivered in the institution, while 25.7% (37) cases were not booked but
      admitted for delivery. The mean age of the parturient and parity were 27.4+/-2.8
      years and 5.8+/-2.4, respectively. The rate of blood splashes was 62.5% on the
      surgeons' masks, 63.2% on surgeons' goggles, 35.4% on assistants' masks, 38.9% on
      assistants' goggles, 11.1% on scrub nurses' masks, and 16.0% on scrub nurses'
      goggles. CONCLUSIONS: We therefore recommend the use of masks and protective eye
      wear as part of routine surgical attire to avoid body fluid contamination that
      can result in acquiring infectious diseases.

PMID- 16449956
TI  - A case of adult-onset type II citrullinemia--deterioration of clinical course
      after infusion of hyperosmotic and high sugar solutions.
AB  - BACKGROUND: Adult-onset type II citrullinemia (CTLN2) is an autosomal recessive
      disorder caused by mutations of SLC25A13 gene encoding citrin and is
      characterized by recurrent encephalopathy with hyperammonemia. Factors affecting
      disease progression remain unknown. We report a case with CTLN2, whose clinical
      course was rapidly worsened by the administration of Glyceol, a hyperosmotic
      diuretic solution consisting of 10% glycerol and 5% fructose in saline. CASE
      REPORT: A 34-year-old man was admitted in coma after repeated episodes of altered
      consciousness. His plasma ammonia level was markedly elevated without any
      evidence of liver diseases. Brain MRI revealed high signal intensities at the
      bilateral cingulate gyri and insular cortices, suggesting hepatic encephalopathy.
      We administered Glyceol. intravenously to alleviate brain edema, however, he
      developed intractable seizures along with steep increase in plasma ammonia levels
      (from 808 to 2210 microg/dL) and died. The diagnosis of CTLN2 was confirmed by
      elevations of plasma citrulline level (384.3 nmol/mL; normal 17-43 nmol/mL) and
      serum pancreatic secretory trypsin inhibitor (PSTI) (110 ng/mL; normal 4.6-12.2
      ng/mL), decrease in hepatic argininosuccinate synthetase activity (5.5% of
      control), lack of hepatic citrin protein expression and mutations in SLC25A13
      gene (compound heterozygote with S225X and Ex1-1G>A). CONCLUSIONS: Physicians
      should take CTLN2 into consideration as a differential diagnosis in Asian
      patients with a history of repeated unconsciousness with hyperammonemia and use D
      mannitol but not glycerol to treat brain edema in patients with CTLN2.

PMID- 16449957
TI  - Paradoxical decrease in blood pressure after relief of cardiac tamponade: the
      role of sympathetic activity.
AB  - BACKGROUND: In contrast to patients who develop acute cardiac tamponade after
      penetrating trauma, tamponade in medical patients may be accompanied by normal or
      even elevated systolic blood pressure. This has been attributed to heightened
      sympathetic nervous system activity. CASE REPORT: We present a case of a medical
      patient with simultaneous hypertension and cardiac tamponade whose blood pressure
      fell dramatically after pericardiocentesis. We observed a decrease in
      normetanephrine levels in our patient concomitant with the decrease in blood
      pressure. CONCLUSIONS: Our case provides further support for involvement of the
      sympathetic nervous system in medical patients with hypertensive tamponade. To
      our knowledge, this is the first case documenting adrenergic status in a patient
      with a paradoxical decrease in blood pressure after relief of tamponade.

PMID- 16449958
TI  - Measurements of objective and subjective fixation disparity with and without a
      central fusion stimulus.
AB  - BACKGROUND: Fixation disparity is the condition in which the images of a
      binocularly fixated object are not imaged on exactly corresponding retinal
      points, but are still within Panum's fusional areas. Measurements of objective
      and subjective fixation disparity have indicated that subjective fixation
      disparity does not indicate the true eye position. However, the effect of the
      foveal fusional lock (FFL) on the relationship between objective and subjective
      fixation disparity is still not clear. MATERIAL/METHODS: This relationship was
      investigated in five subjects. The objective measurements were made using scleral
      search coils, and at the same time the Sheedy distance disparometer indicated the
      subjective fixation disparity. Measurements were obtained both with and without
      an FFL. RESULTS: It was found that without an FFL there was a significant
      difference (p<0.05) between subjective and objective fixation disparity, whereas
      when an FFL was added, the difference was no longer significant. Additionally,
      the absolute sizes of both SFD and OFD were found to be significantly smaller
      with the FFL. CONCLUSIONS: These results indicate that the presence of an FFL
      makes subjective fixation disparity a more accurate indicator of the objective
      eye position. An instrument with an FFL should therefore be used clinically. The
      difference between objective and subjective fixation disparity presumably
      indicates a change in correspondence.

PMID- 16449960
TI  - Integrating theories of the etiology of Crohn's disease. On the etiology of
      Crohn's disease: questioning the hypotheses.
AB  - The most prominent theory describes the Crohn's Syndrome as a dysregulated,
      inappropriate immune response to otherwise innocuous bowel flora in a genetically
      susceptible host. The autoimmune theory assumes that a specific infectious agent
      does not exist. Data from mouse models, impairment of the mucosal epithelial
      barrier and the influence of gut flora are used to support the autoimmune theory.
      Critics claim that the dysregulated immune responses are not the primary disorder
      but secondary to an underlying infection. Two other theories are also consistent
      with the same data. The immunodeficiency theory hypothesizes that defects in
      innate immunity leading to compensatory immune processes underlie the Crohn's
      phenotype and suggests that therapy should stimulate immunity rather than
      suppress it. The mycobacterial theory proposes that Mycobacterium avium
      subspecies paratuberculosis is one of the causes of the Crohn's Disease syndrome.
      Mycobacterial molecules dysregulate immune signaling pathways as part of the
      organisms'evolved survival strategy. If MAP were to initiate the dysregulated
      immune response then the necessity to hypothesize that commensal gut flora
      provide the antigenic stimulus would be moot. Commensal bacteria would be
      relegated to a secondary role of modifying the immune response rather than
      occupying the central role of providing the initiating antigens. Critics claim
      that MAP is merely a secondary invader. The three theories differ primarily by
      emphasizing different aspects of the same overall process.

PMID- 16449959
TI  - Outpatient tinzaparin therapy in pulmonary embolism quantified with
      ventilation/perfusion scintigraphy.
AB  - BACKGROUND: Out-of-hospital treatment of patients with deep-vein thrombosis (DVT)
      is routine in many countries regardless of frequent concomitant asymptomatic
      pulmonary embolism (PE) in this group. However, patients with symptoms and
      verified PE are still regularly treated in hospital. The objectives were to test
      a model for outpatient tinzaparin therapy and to evaluate its safety and efficacy
      in patients with symptomatic, small or medium-sized PE using quantitative
      ventilation/perfusion scintigraphy (qV/P SCINT) for patient selection and follow
      up. MATERIAL/METHODS: This prospective study included 102 patients treated with
      tinzaparin and warfarin for 5 days at a patient hotel. PE was quantified
      scintigraphically as loss of perfusion with preserved ventilation at segmental or
      subsegmental levels (mismatch). Points were attributed to segments of reduced
      ventilation (RoVent) and perfusion (RoPer). A holistic principle of
      interpretation was applied. Patients were excluded if they had >14 RoPer points
      (7 segments) or >7 RoVent points. Clinical follow-up and scintigraphy were
      repeated at discharge in 100 patients and after 13 months on average. RESULTS:
      Embolism diminished by 44% after 5 days and demanding symptoms declined. There
      was no thromboembolic mortality in the trial. At late follow-up, PE had not
      recurred in patients with resolution after 5 days. In those with insufficient
      early response, persistent perfusion defects were usually observed. CONCLUSIONS:
      The results indicate the safety and efficacy of outpatient treatment of PE
      according to our model and merit larger, multicenter, controlled studies.

PMID- 16449961
TI  - Management of hyperlipidemia: new LDL-C targets for persons at high-risk for
      cardiovascular events.
AB  - Coronary heart disease (CHD) remains the leading cause of mortality in the United
      States, and is associated with significant health care costs. Current evidence
      overwhelmingly confirms the role of low-density lipoprotein cholesterol (LDL-C)
      in the pathogenesis of atherosclerosis and the risk of CHD events. The approach
      to the management of hyperlipidemia has evolved dramatically over the past
      decade. Randomized clinical trails have provided strong evidence that lowering
      plasma cholesterol with statins reduces the risk of cardiovascular events,
      particularly in high-risk patients, irrespective of baseline cholesterol levels.
      The National Cholesterol Education Program (NCEP) report was released in July
      2004. The report examined the results of recently concluded clinical trials and
      provided consensus recommendations on the management of hyperlipidemia. The
      report expands on the core content of the previously published guidelines.
      However, it is by far the most aggressive approach to date for reducing CHD risk.
      A focal element of the report is the modification of LDL-C goal in high-risk
      patients to <70 mg/dL. This goal is provided as a therapeutic option and is based
      on findings of recently concluded clinical trials. The more aggressive
      recommendations add challenges to the health care system, as the number of
      patients requiring drug therapy is likely to increase. In spite of the
      challenges, there are ample opportunities for improving the management of
      hyperlipidemia. Adherence to the recommendations will vastly reduce morbidity and
      mortality associated with CHD.

PMID- 16449962
TI  - What influence do major events in life have on our later quality of life? A
      retrospective study on life events and associated emotions.
AB  - BACKGROUND: To examine associations between global quality of life (QOL) and
      major life events. MATERIAL/METHODS: This was a retrospective study using the
      self-administrated expanded SEQOL questionnaire with questions on life events and
      connected emotions. Seven hundred forty-six people, 55-66 years old, from a
      representative sample of the Danish population participated. Global QOL was
      measured by SEQOL (self-evaluation of quality of life), containing eight global
      QOL measures: well-being, life-satisfaction, happiness, fulfillment of needs,
      experience of temporal and spatial domains, expression of life's potentials, and
      objective factors. RESULTS: Life events related to health such as restraints of
      movement or psychological illness showed a major association with the quality of
      life. Most other associations between quality of life and life events were
      intermediate or minor. CONCLUSIONS: Quality of life cannot simply be determined
      by life events. Actual quality of life is determined by how all the events of
      life have been processed and integrated in the consciousness. The results seem to
      support the idea that global QOL can be efficiently improved by integrating the
      painful events of the past. Since several studies have shown correlations between
      QOL and health, it is likely that such an improvement in QOL will also cause
      improved health and ability.

PMID- 16449963
TI  - Total cell associated electrolyte homeostasis in rat spinal cord cells following
      apparently irreversible injury.
AB  - BACKGROUND: We investigated total electrolyte homeostasis in spinal cord cells of
      rats subjected to irreversible spinal cord trauma. MATERIAL/METHODS: Forty-two
      rats underwent total transection of spinal cord (Group 1); chemical neurolysis by
      10% lidocaine overdose (Group 2); sham "injury" (Group 3). Spinal cords were
      isolated 24 h, 72 h or 7 days following injury. Total cellular Ca, Mg, Na and K
      were measured in the spinal cord thoracic or lumbar parts using an atomic
      absorption spectrometer. RESULTS: Group 1: A significant Ca, Mg, Na, and K efflux
      was observed in thoracic and lumbar parts 24 h following transection. By 72 h, a
      significant re-entrance of Ca was evident. By 168 h, an influx of all
      electrolytes was demonstrable, sometimes reaching concentrations above the pre
      trauma levels. Group 2: Following 24 h, Na, K, Ca, and Mg concentrations dropped
      significantly both in thoracic and lumbar parts. By 72 h, the electrolyte re
      entrance was evident in the thoracic, but not the lumbar part. By 168 h, Na, K,
      Ca, and Mg influx was observed both in thoracic and lumbar parts, the
      concentration approaching pre-trauma levels. Group 3: No changes in electrolyte
      content were observed in spinal cords of sham-operated animals. CONCLUSIONS:
      Following massive, apparently irreversible injury of the spinal cord, some
      restorative processes do take place at the cellular level. Subsequent supernormal
      accumulation of intracellular electrolytes, especially Ca, might eventually
      contribute to a secondary injury. Should this be the case, pharmacotherapeutic
      intervention might prove beneficial.

PMID- 16449964
TI  - Co-resistance to retinoic acid and TRAIL by insertion mutagenesis into RAM.
AB  - Retinoic acid (RA), used as first-line therapy for acute promyelocytic leukemia
      (APL), exerts its antileukemic activity by inducing blast differentiation and
      activating tumor-selective TNF-related apoptosis-inducing ligand (TRAIL)
      signaling. To identify downstream mediators of RA signaling, we used retrovirus
      mediated insertion mutagenesis in PLB985 leukemia cells and established the RA
      resistant cell line WY-1. In PLB985, but not WY-1 cells, RA induced TRAIL and its
      DR4 and DR5 receptors. Knocking down TRAIL expression by RNA interference blocked
      RA-induced apoptosis. WY-1 cells are defective for RA-induced differentiation, G1
      arrest and exhibit co-resistance to TRAIL. In WY-1 cells, a single virus copy is
      integrated into a novel RA-regulated gene termed RAM (retinoic acid modulator).
      RAM is expressed in the myelomonocytic lineage and extinguished by RA in PLB985,
      but not WY-1 cells. Whereas knocking down RAM expression by RNA interference
      promoted RA-induced differentiation and TRAIL-triggered apoptosis of PLB985 and
      WY-1 cells, overexpression of the predicted 109 amino-acid RAM open reading frame
      did not alter RA signaling in PLB985 cells. This indicates that, apart from
      encoding the putative RAM protein, RAM RNA may exert additional functions that
      are impaired by the retrovirus insertion. Our study demonstrates that RA
      induction of the TRAIL pathway is also operative in leukemia cells lacking an
      RARalpha oncofusion protein and identifies RAM as a novel RA-dependent modulator
      of myeloid differentiation and death.

PMID- 16449965
TI  - Regulator of G-protein signaling 2 (RGS2) inhibits androgen-independent
      activation of androgen receptor in prostate cancer cells.
AB  - Hormones acting through G protein-coupled receptors (GPCRs) can cause androgen
      independent activation of androgen receptor (AR) in prostate cancer cells.
      Regulators of G-protein signaling (RGS) proteins, through their GTPase activating
      protein (GAP) activities, inhibit GPCR-mediated signaling by inactivating G
      proteins. Here, we identified RGS2 as a gene specifically downregulated in
      androgen-independent prostate cancer cells. Expression of RGS2, but not other RGS
      proteins, abolished androgen-independent AR activity in androgen-independent
      LNCaP cells and CWR22Rv1 cells. In LNCaP cells, RGS2 inhibited G(q)-coupled GPCR
      signaling. Expression of exogenous wild-type RGS2, but not its GAP-deficient
      mutant, significantly reduced AR activation by constitutively activated G(q)Q209L
      mutant whereas silencing endogenous RGS2 by siRNA enhanced G(q)Q209L-stimulated
      AR activity. RGS2 had no effect on RGS-insensitive G(q)Q209L/G188S-induced AR
      activation. Furthermore, extracellular signal-regulated kinase 1/2 (ERK1/2) was
      found to be involved in RGS2-mediated regulation of androgen-independent AR
      activity. In addition, RGS2 functioned as a growth suppressor for androgen
      independent LNCaP cells whereas androgen-sensitive LNCaP cells with RGS2
      silencing had a growth advantage under steroid-reduced conditions. Finally, RGS2
      expression level was significantly decreased in human prostate tumor specimens.
      Taken together, our results suggest RGS2 as a novel regulator of AR signaling and
      its repression may be an important step during prostate tumorigenesis and
      progression.

PMID- 16449966
TI  - Id3 induces a caspase-3- and -9-dependent apoptosis and mediates UVB
      sensitization of HPV16 E6/7 immortalized human keratinocytes.
AB  - Inhibitor of differentiation/DNA binding (Id) proteins comprise a class of helix
      loop-helix transcription factors involved in proliferation, differentiation,
      apoptosis, and carcinogenesis. We have shown that while Id2 is induced by UVB in
      primary keratinocytes, Id3 is upregulated only in immortalized cells. We have now
      determined that the consequences of ectopic expression of Id3 protein are
      strikingly different between immortalized and primary keratinocytes.
      Overexpression of Id3 induces a significant increase in apoptotic cells as
      revealed by Annexin V positivity as well as proteolytic processing of caspase-3
      in immortalized, but not in primary keratinocytes. Id3-green fluorescent protein
      (GFP)-positive cells exhibited a fivefold increase in apoptotic nuclear
      fragmentation compared to Id3-GFP-negative cells. These apoptotic responses were
      accompanied by activation of caspase-3, as shown by immunocytochemical staining
      with antibodies to active caspase-3. Immunostaining with antibodies to the active
      form of caspase-9 as well as to the active form of Bax further revealed that
      induction of apoptosis in Id3-overexpressing keratinocytes occurred via a
      mitochondrial-caspase-9-mediated pathway. Coexpression of dominant-negative
      caspase-9 with Id3 significantly suppressed apoptotic nuclear fragmentation,
      indicating that caspase-9 activation is essential for Id3-induced cell death.
      This response was also markedly attenuated by coexpression with the Bax
      antagonist antiapoptotic protein Bcl2, confirming a role for Bax activation in
      this apoptotic response. Id3-induced Bax activation may result from increased
      expression of Bax protein. Furthermore, reduction of Id3 expression by small
      interfering RNAs abrogated the UVB-induced proteolytic activation of caspase-3 in
      these cells. These data together suggest that UVB-induced apoptosis of
      immortalized keratinocytes is at least in part due to Id3 upregulation in these
      cells.

PMID- 16449967
TI  - Spindle checkpoint protein Bub1 corrects mitotic aberrancy induced by human T
      cell leukemia virus type I Tax.
AB  - Bub1 is a component of the mitotic spindle checkpoint apparatus. Abnormality of
      this apparatus is known to cause multinuclei formation, a hallmark of chromosomal
      instability (CIN). A549, aneuploid cell line, aberrantly passed through the
      mitotic phase and became multinuclei morphology in the presence of nocodazole.
      Time-lapse videomicroscopy showed unreported bizarre morphology, which we named
      'mitotic lobulation' in A549 cells just before the exit from mitosis and
      multinuclei formation. External expression of wild-type Bub1-EGFP clearly
      suppressed the multinuclei formation by retaining A549 cells at the mitotic phase
      during 48 h of time-lapse observation. This suppressive effect on mitotic
      aberrancy should not be mere restoration of normal Bub1 function, because A549
      cells express proper amount of Bub1, which distributed cytoplasm during
      interphase and concentrated at kinetochore in metaphase. Furthermore, external
      expression of wild-type Bub1-EGFP suppressed multinuclei formation induced by Tax
      both in A549 and HeLa cells. Tax is known to induce mitotic abnormality by
      binding and inactivating Mad1. These observations, therefore, suggest functional
      redundancy between Bub1 and other mitotic checkpoint protein(s) and a possibility
      of correction of mitotic aberrancy by external Bub1 expression.

PMID- 16449968
TI  - S100A2 gene is a direct transcriptional target of p53 homologues during
      keratinocyte differentiation.
AB  - The p53 paralogues p73, p63 and their respective truncated isoforms have been
      shown to be critical regulators of developmental and differentiation processes.
      Indeed, both p73- and p63-deficient mice exhibit severe developmental defects.
      Here, we show that S100A2 gene, whose transcript and protein are induced during
      keratinocyte differentiation of HaCaT cells, is a direct transcriptional target
      of p73beta and DeltaNp63alpha and is required for proper keratinocyte
      differentiation. Transactivation assays reveal that p73beta and DeltaNp63alpha
      exert opposite transcriptional effects on S100A2 gene. While DeltaNp63alpha is
      found in vivo onto S100A2 regulatory regions predominantly in proliferating
      cells, p73beta is recruited in differentiating cells. Silencing of p73 impairs
      the induction of S100A2 during the differentiation of HaCaT cells. Moreover,
      silencing of p73 or S100A2 impairs the proper expression of keratinocyte
      differentiation markers. Of note, p53 family members do not trigger S100A2 gene
      expression in response to apoptotic doses of cisplatin and doxorubicin.

PMID- 16449969
TI  - Tumor suppressor menin: the essential role of nuclear localization signal domains
      in coordinating gene expression.
AB  - Menin is encoded by the tumor suppressor gene MEN1 that is mutated in patients
      with an inherited tumor syndrome, multiple endocrine neoplasia type 1 (MEN1).
      Although menin is a nuclear protein and directly binds to DNA through its nuclear
      localization signals (NLSs), the precise role for each of the NLSs in nuclear
      translocation and gene expression remains to be elucidated. Here, we show that
      point mutations in three individual NLSs, NLS1, NLS2, and a novel accessory NLS,
      NLSa, do not block nuclear translocation, but compromise the ability of menin to
      repress expression of the endogenous insulin-like growth factor binding protein-2
      (IGFBP-2) gene. This repression is not released by an inhibitor of histone
      deacetylases. Although subtle mutations in menin NLSs do not affect menin
      association with chromatin, they abolish menin binding to the IGFBP-2 promoter in
      vivo. Furthermore, each of the NLSs is also crucial for menin-mediated induction
      of caspase 8 expression. Together, these results suggest that menin may act as a
      scaffold protein in coordinating activation and repression of gene transcription
      and that its NLSs play a more important role in controlling gene transcription
      than merely targeting menin into the nucleus.

PMID- 16449970
TI  - Effects of hTERT on metal ion-induced genomic instability.
AB  - There is currently a great interest in delayed chromosomal and other damaging
      effects of low-dose exposure to a variety of pollutants which appear collectively
      to act through induction of stress-response pathways related to oxidative stress
      and ageing. These have been studied mostly in the radiation field but evidence is
      accumulating that the mechanisms can also be triggered by chemicals, especially
      heavy metals. Humans are exposed to metals, including chromium (Cr) (VI) and
      vanadium (V) (V), from the environment, industry and surgical implants. Thus, the
      impact of low-dose stress responses may be larger than expected from individual
      toxicity projections. In this study, a short (24 h) exposure of human fibroblasts
      to low doses of Cr (VI) and V (V) caused both acute chromosome damage and genomic
      instability in the progeny of exposed cells for at least 30 days after exposure.
      Acutely, Cr (VI) caused chromatid breaks without aneuploidy while V (V) caused
      aneuploidy without chromatid breaks. The longer-term genomic instability was
      similar but depended on hTERT positivity. In telomerase-negative hTERT- cells, Cr
      (VI) and V (V) caused a long lasting and transmissible induction of dicentric
      chromosomes, nucleoplasmic bridges, micronuclei and aneuploidy. There was also a
      long term and transmissible reduction of clonogenic survival, with an increased
      beta-galactosidase staining and apoptosis. This instability was not present in
      telomerase-positive hTERT+ cells. In contrast, in hTERT+ cells the metals caused
      a persistent induction of tetraploidy, which was not noted in hTERT- cells. The
      growth and survival of both metal-exposed hTERT+ and hTERT- cells differed if
      they were cultured at subconfluent levels or plated out as colonies. Genomic
      instability is considered to be a driving force towards cancer. This study
      suggests that the type of genomic instability in human cells may depend
      critically on whether they are telomerase-positive or -negative and that their
      sensitivities to metals could depend on whether they are clustered or diffuse.

PMID- 16449971
TI  - Inhibition of tumor growth and metastasis in vitro and in vivo by targeting
      macrophage migration inhibitory factor in human neuroblastoma.
AB  - Macrophage migration inhibitory factor (MIF) has been defined as a novel
      oncogene. Our previous results have shown that MIF may contribute to the
      progression of neuroblastoma by (a) inducing N-Myc expression and (b)
      upregulating the expression of angiogenic factors. The aim of this study was to
      test whether tumor growth could be inhibited by reduction of endogenous MIF
      expression in neuroblastoma and clarify the molecular mechanisms underlying MIF
      reduction on the control of neuroblastoma growth. We established human
      neuroblastoma cell lines stably expressing antisense MIF (AS-MIF) cDNA. These
      stable transfectants were characterized by cell proliferation, gene expression
      profile, tumorigenicity and metastasis in vitro and in vivo. Decreased MIF
      expression was observed after transfection with AS-MIF in neuroblastoma cells and
      downregulation of MIF expression significantly correlated with decreased
      expression of N-Myc, Ras, c-Met and TrkB at protein level. Affymetrix microarray
      analysis revealed that expression of IL-8 and c-met was inhibited and
      neuroblastoma-favorable genes such as EPHB6 and BLU were upregulated in MIF
      reduced cells. Neuroblastoma cell growth exhibited a nearly 80% reduction in AS
      MIF transfectants in vitro. Furthermore, mice in which tumors formed after
      subcutaneous injection of AS-MIF transfectants showed a 90% reduction in tumor
      growth compared to control. Metastasis in mice was also suppressed dramatically.
      Our data demonstrate that targeting MIF expression is a promising therapeutic
      strategy in human neuroblastoma therapy, and also identifies the MIF target genes
      for further study.

PMID- 16449972
TI  - Execution of BMP-4-induced apoptosis by p53-dependent ER dysfunction in myeloma
      and B-cell hybridoma cells.
AB  - Bone morphogenic protein (BMP)-4 inhibits proliferation and induces the apoptosis
      of myeloma cells. However, little is known about the molecular mechanisms of how
      BMP-4 executes this apoptosis. In this report, we investigated the roles of p53
      and the endoplasmic reticulum (ER) in BMP-4-induced apoptosis of mouse hybridoma
      HS-72 cells. We found that 3 ng/ml of BMP-4 is sufficient to induce the
      expression of proapoptotic proteins, puma and bax, in a p53-dependent mechanism,
      and facilitate Ca(2+) release from the ER to the cytosol, resulting in the
      activation of caspase-12 and ER dysfunction. Similarly to HS-72 cells, multiple
      myeloma cells with wild-type p53 genes show much higher sensitivity to BMP-4
      induced apoptosis than cells without wild-type p53 genes, suggesting that wild
      type p53 status is required for dysfunction of the ER during BMP-4-induced
      apoptosis in ER-enriched cells, such as hybridoma and myeloma cells. These
      findings demonstrate that the presence of wild-type p53 genes and enrichment of
      the ER determines the sensitivity to effective apoptosis by BMP-4, and suggest
      that ER stress-inducing agents would be valuable in the treatment of multiple
      myeloma.

PMID- 16449973
TI  - BubR1 is involved in regulation of DNA damage responses.
AB  - Defective mitotic spindles or an impaired spindle-kinetochore interaction
      activates the spindle checkpoint. We have previously shown that BubR1 haplo
      insufficiency results in enhanced genomic instability and tumorigenesis in mice.
      Here we report that BubR1 deficiency also leads to a compromised response to DNA
      damage. Following treatment with doxorubicin, BubR1(+/-) murine fibroblast cells
      (MEF) were defective in undergoing G(2)/M arrest. Thus, whereas in the presence
      of DNA damage BubR1(+/+) MEF cells remained arrested in mitosis, BubR1(+/-) MEFs
      rapidly exited from mitosis and divided. The impaired mitotic arrest of BubR1(+/
      ) MEFs was associated with low levels of phospho-histone H2AX, p53, and p21 after
      DNA damage caused by treatment with both doxorubicin and ultraviolet light (UV).
      The impaired expression of p53 and p21 was also confirmed in human cell lines
      with BubR1 knockdown via RNA interference. Affinity pull-down coupled with mass
      spectrometry identified Poly(ADP-ribose) polymerase 1 (PARP-1) as one of the
      proteins interacting with BubR1. Reciprocal co-immunoprecipitation analysis
      confirmed the physical interaction between BubR1 and PARP-1. Our further study
      revealed that the ability of retaining intact PARP-1 or its cleavage product p89
      was compromised in BubR1(+/-) MEFs upon treatment with doxorubicin or UV. Given
      that PARP-1 mediates DNA damage responses and regulates the activity of p53, our
      studies suggest that there exists a cross-talk between the spindle checkpoint and
      the DNA damage checkpoint and that BubR1 may play an important role in mediating
      the cross-talk.

PMID- 16449974
TI  - Loss of one p53 allele results in four-fold reduction of p53 mRNA and protein: a
      basis for p53 haplo-insufficiency.
AB  - A haploid genotype may be insufficient to support normal wild-type function. Such
      haplo-insufficiency has recently been documented for numerous tumour suppressor
      genes. p53 is a crucial tumour suppressor governing DNA repair, cell cycle arrest
      and apoptosis via its role as a stress-responsive transcription factor. p53 haplo
      insufficiency has been observed in vivo with human familial cancer in Li-Fraumeni
      Syndrome (LFS) and in mouse p53-knockout models of LFS. The increased
      tumorigenesis associated with loss of one p53 allele has been attributed to
      reduced p53-dependent stress responses. However, the underlying biochemical basis
      for such attenuated responses in p53+/- cells remains unclear. Here we have
      determined basal p53 messenger RNA (mRNA) and protein levels, and compared the
      p53 stress response in p53+/+, p53+/- and p53-/- isogenic clones derived from
      HCT116 cells. Basal expression of p53 in p53+/- cells was 25% relative to p53+/+
      cells, and this differential was maintained following oncogenic stress. This
      deficiency was manifested at both p53 mRNA and protein levels and resulted in
      attenuated p53 stress responses, in particular for p21waf1 upregulation and
      survivin downregulation, and reduced G1 arrest and apoptosis. These observations
      identify a molecular basis for wild-type p53 haplo-insufficiency, which may
      explain the attenuated tumour-suppressive phenotype observed in cells with a
      single wild-type p53 allele and in humans with LFS.

PMID- 16449975
TI  - Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated
      with unfavourable prognosis.
AB  - The canonical Wnt signalling pathway plays a key role during embryogenesis and
      defects in this pathway have been implicated in the pathogenesis of various types
      of tumours, including breast cancer. The gene for secreted frizzled-related
      protein 1 (SFRP1) encodes a soluble Wnt antagonist and is located in a
      chromosomal region (8p22-p12) that is often deleted in breast cancer. In colon,
      lung, bladder and ovarian cancer SFRP1 expression is frequently inactivated by
      promoter methylation. We have previously shown that loss of SFRP1 protein
      expression is a common event in breast tumours that is associated with poor
      overall survival in patients with early breast cancer. To investigate the cause
      of SFRP1 loss in breast cancer, we performed mutation, methylation and expression
      analysis in human primary breast tumours and breast cell lines. No SFRP1 gene
      mutations were detected. However, promoter methylation of SFRP1 was frequently
      observed in both primary breast cancer (61%, n=130) and cell lines analysed by
      methylation-specific polymerase chain reaction (MSP). We found a tight
      correlation (P<0.001) between methylation and loss of SFRP1 expression in primary
      breast cancer tissue. SFRP1 expression was restored after treatment of tumour
      cell lines with the demethylating agent 5-aza-2'-deoxycytidine. Most
      interestingly, SFRP1 promoter methylation was an independent factor for adverse
      patient survival in Kaplan-Meier analysis. Our results indicate that promoter
      hypermethylation is the predominant mechanism of SFRP1 gene silencing in human
      breast cancer and that SFRP1 gene inactivation in breast cancer is associated
      with unfavourable prognosis.

PMID- 16449976
TI  - Transcriptional profiling suggests that Barrett's metaplasia is an early
      intermediate stage in esophageal adenocarcinogenesis.
AB  - To investigate the relationship between Barrett's esophagus (BE) and esophageal
      adenocarcinoma (EAC), we determined gene expression profiles of discrete
      pathological stages of esophageal neoplasia using a sequence-verified human cDNA
      microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine
      EACs were hybridized to cDNA microarrays. Five statistical analyses were used for
      the data analysis. Genes showing significantly different expression levels among
      the three sample groups were identified. Genes were grouped into functional
      categories based on the Gene Ontology Consortium. Surprisingly, the expression
      pattern of BE was significantly more similar to EAC than to NE, notwithstanding
      the known histopathologic differences between BE and EAC. The pattern of NE was
      clearly distinct from that of EAC. Thirty-six genes were the most differentially
      modulated, according to these microarray data, in BE-associated neoplastic
      progression. Twelve genes were significantly differentially expressed in cancer
      associated BE's plus EAC (as a single combined tissue group) vs noncancer
      associated BE's. These genes represent potential biomarkers to diagnose EAC at
      its early stages. Our results demonstrate that molecular events at the
      transcriptional level in BE are remarkably similar to BE's-associated
      adenocarcinoma of the esophagus. This finding alarmingly implies that BE is
      biologically closer to cancer than to normal esophagus, and that the cancer risk
      of BE is perhaps higher than we had imagined. These findings suggest that changes
      modulated at the molecular biologic level supervene earlier than histologic
      changes, and that BE is an early intermediate stage in the process of EAC.

PMID- 16449977
TI  - Highly purified CD44+ prostate cancer cells from xenograft human tumors are
      enriched in tumorigenic and metastatic progenitor cells.
AB  - CD44 is a multifunctional protein involved in cell adhesion and signaling. The
      role of CD44 in prostate cancer (PCa) development and progression is
      controversial with studies showing both tumor-promoting and tumor-inhibiting
      effects. Most of these studies have used bulk-cultured PCa cells or PCa tissues
      to carry out correlative or overexpression experiments. The key experiment using
      prospectively purified cells has not been carried out. Here we use FACS to obtain
      homogeneous CD44(+) and CD44(-) tumor cell populations from multiple PCa cell
      cultures as well as four xenograft tumors to compare their in vitro and in vivo
      tumor-associated properties. Our results reveal that the CD44(+) PCa cells are
      more proliferative, clonogenic, tumorigenic, and metastatic than the isogenic
      CD44(-) PCa cells. Subsequent molecular studies demonstrate that the CD44(+) PCa
      cells possess certain intrinsic properties of progenitor cells. First, BrdU pulse
      chase experiments reveal that CD44(+) cells colocalize with a population of
      intermediate label-retaining cells. Second, CD44(+) PCa cells express higher mRNA
      levels of several 'stemness' genes including Oct-3/4, Bmi, beta-catenin, and SMO.
      Third, CD44(+) PCa cells can generate CD44(-) cells in vitro and in vivo. Fourth,
      CD44(+) PCa cells, which are AR(-), can differentiate into AR(+) tumor cells.
      Finally, a very small percentage of CD44(+) PCa cells appear to undergo
      asymmetric cell division in clonal analyses. Altogether, our results suggest that
      the CD44(+) PCa cell population is enriched in tumorigenic and metastatic
      progenitor cells.

PMID- 16449979
TI  - The green tea catechins, (-)-Epigallocatechin-3-gallate (EGCG) and (-)
      Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and
      tumorigenic breast epithelial cells.
AB  - The hepatocyte growth factor (HGF) receptor, Met, is a strong prognostic
      indicator of breast cancer patient outcome and survival, suggesting that
      therapies targeting Met may have beneficial outcomes in the clinic. (-)
      Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been
      recognized as a potential therapeutic agent. We assessed the ability of EGCG to
      inhibit HGF signaling in the immortalized, nontumorigenic breast cell line,
      MCF10A, and the invasive breast carcinoma cell line, MDA-MB-231. HGF treatment in
      both cell lines induced rapid, sustained activation of Met, ERK and AKT.
      Pretreatment of cells with concentrations of EGCG as low as 0.3 microM inhibited
      HGF-induced Met phosphorylation and downstream activation of AKT and ERK.
      Treatment with 5.0 microM EGCG blocked the ability of HGF to induce cell motility
      and invasion. We assessed the ability of alternative green tea catechins to
      inhibit HGF-induced signaling and motility. (-)-Epicatechin-3-gallate (ECG)
      functioned similar to EGCG by completely blocking HGF-induced signaling as low as
      0.6 microM and motility at 5 microM in MCF10A cells; whereas, (-)-epicatechin
      (EC) was unable to inhibit HGF-induced events at any concentration tested. (-)
      Epigallocatechin (EGC), however, completely repressed HGF-induced AKT and ERK
      phosphorylation at concentrations of 10 and 20 microM, but was incapable of
      blocking Met activation. Despite these observations, EGC did inhibit HGF-induced
      motility in MCF10A cells at 10 microM. These observations suggest that the R1
      galloyl and the R2 hydroxyl groups are important in mediating the green tea
      catechins' inhibitory effect towards HGF/Met signaling. These combined in vitro
      studies reveal the possible benefits of green tea polyphenols as cancer
      therapeutic agents to inhibit Met signaling and potentially block invasive cancer
      growth.

PMID- 16449980
TI  - Evolutionary population genetics: were the Vikings immune to HIV?

PMID- 16449978
TI  - Implications of increased tissue transglutaminase (TG2) expression in drug
      resistant breast cancer (MCF-7) cells.
AB  - The development of resistance to chemotherapeutic drugs is a major obstacle to
      the successful treatment of breast cancer. Ways to block or overcome this
      resistance are objects of intense research. We have previously shown that cancer
      cells selected for resistance against chemotherapeutic drugs or isolated from
      metastatic tumor sites have high levels of a calcium-dependent protein
      crosslinking enzyme, tissue transglutaminase (TG2) but no direct link between TG2
      and resistance was established. As TG2 can associate with the beta members of the
      integrin family of proteins, we hypothesized that TG2 promotes cell survival
      signaling pathways by activating integrins on the surface of these cells. To test
      this hypothesis, we studied the expression of TG2 and its interaction with
      various integrins in drug-resistant MCF-7 breast cancer cells. TG2 closely
      associated with beta1 and beta5 integrins on the surface of drug-resistant MCF-7
      (MCF-7/Dox and MCF-7/RT) cells. The incubation of TG2-expressing drug-resistant
      MCF-7 cells on fibronectin (Fn)-coated surfaces strongly activated focal adhesion
      kinase, an event that leads to the activation of several downstream signaling
      pathways and, in turn, can confer apoptosis-resistant phenotype to cancer cells.
      The role of TG2 in Fn-mediated cell attachment, cell growth, and cell survival
      functions was further analysed by small interfering RNA (siRNA) approach.
      Inhibition of TG2 by siRNA-inhibited Fn-mediated cell attachment and cell
      survival functions in drug-resistant MCF-7 cells. We conclude that the expression
      of TG2 in breast cancer cells contributes to the development of the drug
      resistance phenotype by promoting interaction between integrins and Fn.

PMID- 16449981
TI  - Mating patterns and demography in the tristylous daffodil Narcissus triandrus.
AB  - Mating patterns in plant populations are influenced by interactions between
      reproductive traits and ecological conditions, both factors that are likely to
      vary geographically. Narcissus triandrus, a wide-ranging heterostylous herb,
      exhibits populations with either two (dimorphic) or three (trimorphic) style
      morphs and displays substantial geographical variation in demographic attributes
      and floral morphology. Here, we investigate this variation to determine if
      demography, morphology, and mating system differ between the two sexual systems.
      Our surveys in Portugal and NW Spain indicated that dimorphic populations were
      less dense, of smaller size, and had larger plants and flowers compared to
      trimorphic populations. Outcrossing rates estimated using allozyme markers
      revealed similar outcrossing rates in dimorphic and trimorphic populations (t(m)
      dimorphic=0.759; t(m) trimorphic=0.710). All populations experienced significant
      inbreeding in progeny (mean F=0.143). In contrast, parental estimates of
      inbreeding were not significantly different from zero (mean F=0.062), implying
      that few inbred offspring survive to reproductive maturity due to inbreeding
      depression. Although the majority of inbreeding results from selfing, significant
      levels of biparental inbreeding were also detected in eight of the nine
      populations (mean s(s)-s(m)=0.081). Density was negatively associated with levels
      of selfing but positively associated with biparental inbreeding. Population size
      was positively associated with outcrossing but not biparental inbreeding. There
      were no consistent differences among the style morphs in outcrossing or
      biparental inbreeding indicating that the maintenance of trimorphism vs
      dimorphism is unlikely to be associated with inbreeding of maternal parents.

PMID- 16449982
TI  - The rise and falls of introns.
AB  - There has been a lively debate over the evolution of eukaryote introns: at what
      point in the tree of life did they appear and from where, and what has been their
      subsequent pattern of loss and gain? A diverse range of recent research papers is
      relevant to this debate, and it is timely to bring them together. The absence of
      introns that are not self-splicing in prokaryotes and several other lines of
      evidence suggest an ancient eukaryotic origin for these introns, and the
      subsequent gain and loss of introns appears to be an ongoing process in many
      organisms. Some introns are now functionally important and there have been
      suggestions that invoke natural selection for the ancient and recent gain of
      introns, but it is also possible that fixation and loss of introns can occur in
      the absence of positive selection.

PMID- 16449985
TI  - Materials needs for fusion.

PMID- 16449984
TI  - Chloroplast DNA phylogeography of the arctic-montane species Saxifraga hirculus
      (Saxifragaceae).
AB  - The genetic structure of populations of an arctic-montane herb, Saxifraga
      hirculus (Saxifragaceae), was analysed by means of chloroplast restriction
      fragment-length polymorphism. Sampled populations were distributed across Europe
      and North America (Alaska and Colorado). There was no evidence for geographically
      structured genetically divergent lineages, and although no haplotypes were shared
      between North America and Europe, the haplotypes from different continents were
      intermixed on a minimum spanning tree. European populations were much more highly
      differentiated and had much lower levels of haplotype diversity than their
      Alaskan counterparts. Centres of haplotype diversity were concentrated in those
      Alaskan populations located outside the limits of the last (Wisconsin)
      glaciation, suggesting that they may have acted as refugia during the
      Pleistocene. It was not possible to identify putative migration routes or
      corresponding refugia in the European genepool. One British population, from the
      Pentland Hills, was genetically very distant from all the others, for reasons
      that are as yet unknown.

PMID- 16449983
TI  - GISH/FISH mapping of genes for freezing tolerance transferred from Festuca
      pratensis to Lolium multiflorum.
AB  - The first backcross breeding programme for the transfer of freezing-tolerance
      genes from winter hardy Festuca pratensis to winter-sensitive Lolium multiflorum
      is described. A partly fertile, triploid F(1) hybrid F. pratensis (2n=2x=14) x L.
      multiflorum (2n=4x=28) was employed initially, and after two backcrosses to L.
      multiflorum (2x) a total of 242 backcross two (BC(2)) plants were generated.
      Genomic in situ hybridisation (GISH) was performed on 61 BC(2) plants selected
      for their good growth and winter survival characters in the spring following one
      Polish winter (2000-2001). Among the winter survivors, diploid chromosome numbers
      were present in 80% of plants. An appropriate single Festuca introgression in an
      otherwise undisturbed Lolium genome could provide increased freezing tolerance
      without compromise to the good growth and plant vigour found in Lolium. Among all
      the diploids, a total of 20 individuals were identified, each with a single F.
      pratensis chromosome segment. Another diploid plant contained 13 Lolium
      chromosomes and a large metacentric F. pratensis chromosome, identified as
      chromosome 4, with two large distal Lolium introgressions on each chromosome arm.
      Three of the diploid BC(2), including the genotype with Festuca chromosome 4 DNA
      sequences, were found to have freezing tolerance in excess of that of L.
      multiflorum, and in one case in excess of the F. pratensis used as control. A
      detailed cytological analysis combining GISH and fluorescence in situ
      hybridisation analyses with rDNA probes revealed that the other two freezing
      tolerant genotypes carried a Festuca chromosome segment at the same terminal
      location on the non-satellite arm of Lolium chromosome 2.

PMID- 16449986
TI  - Materials research for fusion energy.

PMID- 16449988
TI  - Photonic crystals: straightening out light.

PMID- 16449989
TI  - Colloidal crystals: plenty of room at the top.

PMID- 16449990
TI  - Magnetic materials: compensating for bias.

PMID- 16449991
TI  - Electrochromic materials: out of a niche.

PMID- 16449992
TI  - Two-dimensional crystals: through the looking glass.

PMID- 16449993
TI  - Material witness: no nails.

PMID- 16449994
TI  - Prevalence of serologic reactivity against four strains of mouse mammary tumour
      virus among US women with breast cancer.
AB  - Mouse mammary tumour virus (MMTV) causes breast cancer in mice, and MMTV-specific
      antibodies develop to high titers among mice infected as adults. Whether MMTV or
      a related virus infects humans is uncertain, because MMTV DNA sequences have been
      detected inconsistently and because serologic methods have varied widely. The
      current study used immunoblot and immunoprecipitation with four strains of MMTV
      (RIII, FM, C3H, and LA) to detect specific antibodies in 92 sera from US women
      with breast cancer and in masked dilutions of monoclonal hybridoma and
      hyperimmunised goat positive-control reagents. In these positive controls, MMTV
      antibodies of the expected molecular weights were detected at high titer (1 : 100
      in the monoclonal reagent, 1 : 10000 in the hyperimmunised goat serum). Nearly
      30% of the sera from women with breast cancer had at least one faint band on an
      immunoblot, but none of these matched the molecular weight of bands revealed by
      probing the same blot strips with the goat serum. The goat serum readily
      immunoprecipitated MMTV antigens from all four strains of MMTV, but MMTV antigens
      were not immunoprecipitated by any of the six breast cancer sera that had four or
      more nonspecific immunoblot bands. Thus, among women with breast cancer, we found
      no MMTV-specific antibodies. The upper 95% confidence limit implies that MMTV
      seroprevalence among breast cancer patients does not exceed 3%.

PMID- 16449995
TI  - Quality of life and cost-effectiveness of interferon-alpha in malignant melanoma:
      results from randomised trial.
AB  - A definitive conclusion regarding the value of low-dose extended duration
      adjuvant interferon-alpha therapy in the treatment of malignant melanoma is only
      possible once data on health-related quality of life (HRQoL) and costs have been
      considered. This trial randomised 674 patients to interferon alpha-2a (3
      megaunits three times per week for 2 years or until recurrence) or placebo.
      Health-related quality of life (QoL) was to be assessed up to 60 months using the
      European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Data
      for the economic analysis, including cost information and the EQ-5D were also
      collected. Patients in the observation (OBS) group had significantly better mean
      follow-up quality of on five dimensions of the EORTC QLQ-C30 functional scales:
      role functioning (P = 0.033), emotional functioning (P = 0.003), cognitive
      functioning (P = 0.001), social functioning (P = 0.003) and global health status
      (P = 0.001). Patients in the OBS group had significantly better mean follow-up
      symptom scores on seven dimensions of the EORTC QLQ-C30 V1 symptom scales.
      Economic data showed that costs were 3066 pounds higher in the interferon group
      and produces an incremental cost per quality-adjusted life year of 41,432 pounds
      at 5 years. The results show that interferon has significant effects on QoL and
      symptomatology and is unlikely to be cost-effective in this patient group in the
      UK.

PMID- 16449996
TI  - Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in
      oral cancer: quantitative evaluation using pyrosequencing.
AB  - Methylation profiling of cancer tissues has identified this mechanism as an
      important component of carcinogenesis. Epigenetic silencing of tumour suppressor
      genes through promoter methylation has been investigated by a variety of means,
      the most recent of which is pyrosequencing. We have investigated quantitative
      methylation status in oral squamous cell carcinoma patients. Fresh tumour tissue
      and normal control tissue from resection margin was obtained from 79 consecutive
      patients undergoing resection of oral squamous cell carcinoma. DNA was extracted
      and bisulphite treated. PCR primers were designed to amplify 75-200 bp regions of
      the CpG rich gene promoters of p16, RARbeta, E-cadherin, cytoglobin and cyclinA1.
      Methylation status of 4-5 CpG sites per gene was determined by pyrosequencing.
      Significant CpG methylation of gene promoters within tumour specimens was found
      in 28% for p16, 73% for RARbeta, 42% for E-cadherin, 65% for cytoglobin and 53%
      for cyclinA1. Promoter methylation was significantly elevated in tumours compared
      to normal tissue for p16 (P = 0.048), cytoglobin (P = 0.002) and cyclin A1 (P =
      0.001) but not in RARbeta (P = 0.088) or E-cadherin (P = 0.347). Concordant
      methylation was demonstrated in this tumour series (P = 0.03). Significant
      differences in degree of methylation of individual CpG sites were noted for all
      genes except RARbeta and these differences were in a characteristic pattern that
      was reproduced between tumour samples. Cyclin A1 promoter methylation showed an
      inverse trend with histological grade. Promoter methylation analysis using
      pyrosequencing reveals valuable quantitative data from several CpG sites. In
      contrast to qualitative data generated from methylation specific PCR, our data
      demonstrated p16 promoter methylation in a highly tumour specific pattern.
      Significant tumour specific methylation of cyclin A1 promoter was also seen.
      Cytoglobin is a novel candidate tumour suppressor gene highly methylated in upper
      aero-digestive tract squamous cancer.

PMID- 16449997
TI  - Inhibitory effects of retinoic acid metabolism blocking agents (RAMBAs) on the
      growth of human prostate cancer cells and LNCaP prostate tumour xenografts in
      SCID mice.
AB  - In recent studies, we have identified several highly potent all-trans-retinoic
      acid (ATRA) metabolism blocking agents (RAMBAs). On the basis of previous effects
      of liarozole (a first-generation RAMBA) on the catabolism of ATRA and on growth
      of rat Dunning R3227G prostate tumours, we assessed the effects of our novel
      RAMBAs on human prostate tumour (PCA) cell lines. We examined three different PCA
      cell lines to determine their capacity to induce P450-mediated oxidation of ATRA.
      Among the three different cell lines, enhanced catabolism was detected in LNCaP,
      whereas it was not found in PC-3 and DU-145. This catabolism was strongly
      inhibited by our RAMBAs, the most potent being VN/14-1, VN/50-1, VN/66-1, and
      VN/69-1 with IC50 values of 6.5, 90.0, 62.5, and 90.0 nM, respectively. The
      RAMBAs inhibited the growth of LNCaP cells with IC50 values in the microM-range.
      In LNCaP cell proliferation assays, VN/14-1, VN/50-1, VN/66-1, and VN/69-1 also
      enhanced by 47-, 60-, 70-, and 65-fold, respectively, the ATRA-mediated
      antiproliferative activity. We then examined the molecular mechanism underlying
      the growth inhibitory properties of ATRA alone and in combination with RAMBAs.
      The mechanism appeared to involve the induction of differentiation, cell-cycle
      arrest, and induction of apoptosis (TUNEL), involving increase in Bad expression
      and decrease in Bcl-2 expression. Treatment of LNCaP tumours growing in SCID mice
      with VN/66-1 and VN/69-1 resulted in modest but statistically significant tumour
      growth inhibition of 44 and 47%, respectively, while treatment with VN/14-1 was
      unexpectedly ineffective. These results suggest that some of our novel RAMBAs may
      be useful agents for the treatment of prostate cancer.

PMID- 16449998
TI  - Mutation of the PIK3CA oncogene in human cancers.
AB  - It is now well established that cancer is a genetic disease and that somatic
      mutations of oncogenes and tumour suppressor genes are the initiators of the
      carcinogenic process. The phosphatidylinositol 3-kinase signalling pathway has
      previously been implicated in tumorigenesis, and evidence over the past year
      suggests a pivotal role for the phosphatidylinositol 3-kinase catalytic subunit,
      PIK3CA, in human cancers. In this review, we analyse recent reports describing
      PIK3CA mutations in a variety of human malignancies, and discuss their possible
      implications for diagnosis and therapy.

PMID- 16449999
TI  - Transcriptional profiling of Epstein-Barr virus (EBV) genes and host cellular
      genes in nasal NK/T-cell lymphoma and chronic active EBV infection.
AB  - Nasal NK/T-cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma (NHL)
      that is closely associated with Epstein-Barr virus (EBV). The clonal expansion of
      EBV-infected NK or T cells is also seen in patients with chronic active EBV
      (CAEBV) infection, suggesting that two diseases might share a partially similar
      mechanism by which EBV affects host cellular gene expression. To understand the
      pathogenesis of EBV-associated NK/T-cell lymphoproliferative disorders (LPD) and
      design new therapies, we employed a novel EBV DNA microarray to compare patterns
      of EBV expression in six cell lines established from EBV-associated NK/T-cell
      LPD. We found that expression of BZLF1, which encodes the immediate-early gene
      product Zta, was expressed in SNK/T cells and the expression levels were
      preferentially high in cell lines from CAEBV infection. We also analyzed the gene
      expression patterns of host cellular genes using a human oligonucleotide DNA
      microarray. We identified a subset of pathogenically and clinically relevant host
      cellular genes, including TNFRSF10D, CDK2, HSPCA, IL12A as a common molecular
      biological properties of EBV-associated NK/T-cell LPD and a subset of genes, such
      as PDCD4 as a putative contributor for disease progression. This study describes
      a novel approach from the aspects of viral and host gene expression, which could
      identify novel therapeutic targets in EBV-associated NK/T-cell LPD.

PMID- 16450001
TI  - FADD phosphorylation is critical for cell cycle regulation in breast cancer
      cells.
AB  - Anti-oestrogen therapy is effective for control of hormone receptor-positive
      breast cancers, although the detailed molecular mechanisms, including signal
      transduction, remain unclear. We demonstrated here that long-term tamoxifen
      treatment causes G2/M cell cycle arrest through c-jun N-terminal kinase (JNK)
      activation, which is dependent on phosphorylation of Fas-associated death domain
      containing protein (FADD) at 194 serine in an oestrogen (ER) receptor-positive
      breast cancer cell line, MCF-7. Expression of a dominant negative mutant form of
      MKK7, a kinase upstream of JNK, or mutant FADD (S194A) in MCF-7 cells suppressed
      the cytotoxicity of long-term tamoxifen treatment. Of great interest, similar
      signallings could be evoked by paclitaxel, even in an ER-negative cell line, MDA
      MB-231. In addition, immunohistochemical analysis using human breast cancer
      specimens showed a close correlation between phosphorylated JNK and FADD
      expression, both being significantly reduced in cases with metastatic potential.
      We conclude that JNK-mediated phosphorylation of FADD plays an important role in
      the negative regulation of cell growth and metastasis, independent of the ER
      status of a breast cancer, so that JNK/FADD signals might be promising targets
      for cancer therapy.

PMID- 16450000
TI  - Targeting insulin-like growth factor pathways.
AB  - Some cancer cells depend on the function of specific molecules for their growth,
      survival, and metastatic potential. Targeting of these critical molecules has
      arguably been the best therapy for cancer as demonstrated by the success of
      tamoxifen and trastuzumab in breast cancer. This review will evaluate the type I
      IGF receptor (IGF-IR) as a potential target for cancer therapy. As new drugs come
      forward targeting this receptor system, several issues will need to be addressed
      in the early clinical trials using these agents.

PMID- 16450003
TI  - Beautification and fraud.

PMID- 16450002
TI  - Circulating endothelial cells and angiogenic serum factors during neoadjuvant
      chemotherapy of primary breast cancer.
AB  - Circulating endothelial cells (CECs) as well as bone-marrow-derived endothelial
      precursor cells (EPC) play an important role in neovascularisation and tumour
      growth. To study the impact of neoadjuvant chemotherapy on the amounts of CEC and
      their precursor cells, mature CEC and their progenitors were quantified by flow
      cytometry in peripheral blood of breast cancer patients during anthracycline
      and/or taxane based neoadjuvant chemotherapy and subsequent surgery in comparison
      to age-matched healthy controls. Cell numbers were tested for correlation with
      serum levels of angiopoietin-2, erythropoietin, endostatin, endoglin, VEGF and
      sVCAM-1 as well as clinical and pathological features of breast cancer disease.
      Circulating endothelial cells were significantly elevated in breast cancer
      patients and decreased during chemotherapy, whereas EPC (CD34+/VEGFR-2+) as well
      as their progenitor cell population CD133+/CD34+ and the population of CD34+ stem
      cells increased. Concomitantly with the increase of progenitor cells an increase
      of VEGF, erythropoietin and angiopoietin-2 was observed. These data suggest that
      chemotherapy can only reduce the amounts of mature CEC, probably reflecting
      detached cells from tumour vessels, whereas the EPC and their progenitors are
      mobilised by chemotherapy. Since this mobilisation of EPC may contribute to
      tumour neovascularisation an early antiangiogenic therapy in combination with
      chemotherapy could be beneficial for the success of cancer therapy.

PMID- 16450005
TI  - V-ATPase: a potential pH sensor.

PMID- 16450004
TI  - The transcellular railway: insights into leukocyte diapedesis.

PMID- 16450006
TI  - INCENP at the kinase crossroads.

PMID- 16450007
TI  - microRNA signals cell fate.

PMID- 16450011
TI  - Hepcidin--the iron regulatory hormone.

PMID- 16450010
TI  - A Role for the SmpB-SsrA system in Yersinia pseudotuberculosis pathogenesis.
AB  - Yersinia utilizes a sophisticated type III secretion system to enhance its
      chances of survival and to overcome the host immune system. SmpB (small protein
      B) and SsrA (small stable RNA A) are components of a unique bacterial
      translational control system that help maintain the bacterial translational
      machinery in a fully operational state. We have found that loss of the SmpB-SsrA
      function causes acute defects in the ability of Yersinia pseudotuberculosis to
      survive in hostile environments. Most significantly, we show that mutations in
      smpB-ssrA genes render the bacterium avirulent and unable to cause mortality in
      mice. Consistent with these observations, we show that the mutant strain is
      unable to proliferate in macrophages and exhibits delayed Yop-mediated host cell
      cytotoxicity. Correspondingly, we demonstrate that the smpB-ssrA mutant suffers
      severe deficiencies in expression and secretion of Yersinia virulence effector
      proteins, and that this defect is at the level of transcription. Of further
      interest is the finding that the SmpB-SsrA system might play a similar role in
      the related type III secretion system that governs flagella assembly and
      bacterial motility. These findings highlight the significance of the SmpB-SsrA
      system in bacterial pathogenesis, survival under adverse environmental
      conditions, and motility.

PMID- 16450009
TI  - Pol II-expressed shRNA knocks down Sod2 gene expression and causes phenotypes of
      the gene knockout in mice.
AB  - RNA interference (RNAi) has been used increasingly for reverse genetics in
      invertebrates and mammalian cells, and has the potential to become an alternative
      to gene knockout technology in mammals. Thus far, only RNA polymerase III (Pol
      III)-expressed short hairpin RNA (shRNA) has been used to make shRNA-expressing
      transgenic mice. However, widespread knockdown and induction of phenotypes of
      gene knockout in postnatal mice have not been demonstrated. Previous studies have
      shown that Pol II synthesizes micro RNAs (miRNAs)-the endogenous shRNAs that
      carry out gene silencing function. To achieve efficient gene knockdown in mammals
      and to generate phenotypes of gene knockout, we designed a construct in which a
      Pol II (ubiquitin C) promoter drove the expression of an shRNA with a structure
      that mimics human miRNA miR-30a. Two transgenic lines showed widespread and
      sustained shRNA expression, and efficient knockdown of the target gene Sod2.
      These mice were viable but with phenotypes of SOD2 deficiency. Bigenic
      heterozygous mice generated by crossing these two lines showed nearly
      undetectable target gene expression and phenotypes consistent with the target
      gene knockout, including slow growth, fatty liver, dilated cardiomyopathy, and
      premature death. This approach opens the door of RNAi to a wide array of well
      established Pol II transgenic strategies and offers a technically simpler,
      cheaper, and quicker alternative to gene knockout by homologous recombination for
      reverse genetics in mice and other mammalian species.

PMID- 16450013
TI  - Preparing the biochemistry laboratory for the next outbreak: lessons from SARS in
      Singapore.
AB  - Severe acute respiratory syndrome (SARS) is an emerging disease characterised by
      fever and atypical pneumonia and caused by a novel coronavirus. Singapore was
      affected by the global pandemic in early 2003, with 238 cases and 33 deaths.
      Samples sent to the biochemistry laboratory made up the majority (69%) of all
      SARS samples, yet remained a minority (29%) of total biochemistry workload. This
      paper describes the problems encountered and solutions adopted by the
      biochemistry laboratory at the designated SARS hospital in coping with this
      epidemic. It provides practical advice for laboratories planning for the handling
      of samples from future outbreaks.

PMID- 16450012
TI  - Metabolic syndrome and type 2 diabetes: the Hong Kong perspective.
AB  - The Metabolic syndrome (MetS), obesity and type 2 diabetes are growing global
      epidemics especially in Asian populations. In light of the differences in body
      build between people from the West and the East, definitions of obesity in Asians
      have been modified accordingly. Data from Hong Kong, an epitome of future China,
      may provide important insight into the potential interactions between nature and
      nurture in this global epidemic. Now supported by large scale studies, it is
      clear that Chinese type 2 diabetic patients exhibit marked phenotypic
      heterogeneity in terms of risk profiles and complications. Apart from genetic
      differences, age- and stress-related neurohormonal dysregulation may also
      contribute to the increasing prevalence of obesity, type 2 diabetes and MetS in
      Chinese living in modern societies. In this mini-review, we aim to summarise
      findings from our group collected during the last decade in our attempt to
      understand this epidemic and to develop evidence-based care models to reduce the
      impact of this health hazard.

PMID- 16450015
TI  - Chronic kidney disease and automatic reporting of estimated glomerular filtration
      rate: a position statement.
AB  - The systematic staging of chronic kidney disease (CKD) by glomerular filtration
      measurement and proteinuria has allowed the development of rational and
      appropriate management plans. One of the barriers to early detection of CKD is
      the lack of a precise, reliable and consistent measure of kidney function. The
      most common measure of kidney function is currently serum creatinine
      concentration. It varies with age, sex, muscle mass and diet, and interlaboratory
      variation between measurements is as high as 20%. The reference interval for
      serum creatinine concentration includes up to 25% of people (particularly thin,
      elderly women) who have an estimated glomerular filtration rate (eGFR) that is
      significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated
      formula (MDRD) to estimate GFR from age, sex, race and serum creatinine
      concentration, without any requirement for measures of body mass, allows
      pathology laboratories to "automatically" generate eGFR from data already
      acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine
      measurements would help to identify asymptomatic kidney dysfunction at an earlier
      stage. eGFR correlates well with complications of CKD and an increased risk of
      adverse outcomes such as cardiovascular morbidity and mortality. We recommend
      that pathology laboratories automatically report eGFR each time a serum
      creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in
      patients with normal or near-normal renal function, we recommend that calculated
      eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m",
      rather than as a precise figure.

PMID- 16450014
TI  - Recent developments in the first detection of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) ranks fifth in frequency of cancers worldwide. The
      main aetiological factor is hepatitis B virus (HBV) although the importance of
      hepatitis C virus (HCV) is growing. The most important tumour marker for HCC is
      alpha-fetoprotein (AFP). The common method of screening high risk patients by AFP
      and ultrasonography has been shown to result in earlier detection and
      consequently more easily treatable tumours and longer survival. Proposed
      screening interval varies from once every 3 months to annually to "as indicated'
      but, most commonly, is once every 6 months. AFP is a fairly specific but
      insensitive marker for HCC. Sensitivity of HCC detection by blood markers is
      improved by combining various other markers with AFP. Of the other markers, the
      newer high sensitivity des-gamma-carboxy-prothrombin (DCP) has been found to be
      useful. In addition the AFP fractions L3, P4/5 and the +II band are highly
      specific for HCC. Among routinely assayed tumour markers in the laboratory, CA
      125 is more sensitive for HCC than AFP but far less specific. Various other
      enzymes, isoenzymes, growth factors, adhesion molecules, other proteins such as
      interleukin-2 receptor (IL-2R), human cervical cancer oncogene protein (HCCR) and
      glypican-3 (GPC3), p15 and p16 hypermethylation and nitrite/nitrate ratio have
      been tested; some of these show promise but none is presently in routine use. The
      value of other newer markers such as the HBx protein that is produced by HBV, and
      what are thought to be specific proteins and signatures identified by proteomics
      remain to be determined.

PMID- 16450017
TI  - Rationale, design and baseline characteristics of a large, simple, randomized
      trial of combined folic acid and vitamins B6 and B12 in high-risk patients: the
      Heart Outcomes Prevention Evaluation (HOPE)-2 trial.
AB  - BACKGROUND: Epidemiological studies suggest that mild to moderate elevation in
      plasma homocysteine concentration is associated with increased risk of
      atherothrombotic cardiovascular (CV) disease. Simple, inexpensive and nontoxic
      therapy with folic acid and vitamins B6 and B12 reduces plasma homocysteine
      levels by approximately 25% to 30% and may reduce CV events. Therefore, a large,
      randomized clinical trial--the Heart Outcomes Prevention Evaluation (HOPE)-2
      study--is being conducted to evaluate this therapy in patients at high risk for
      CV events. OBJECTIVES: To evaluate whether long-term therapy with folic acid and
      vitamins B6 and B12 reduces the risk of major CV events in a high-risk
      population. The primary study outcome is the composite of death from CV causes,
      myocardial infarction and stroke. METHODS: A total of 5522 patients aged 55 years
      or older with pre-existing CV disease or with diabetes and additional risk
      factor(s) at 145 centres in 13 countries were randomly assigned to daily therapy
      with combined folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg, or to
      placebo. Follow-up will average five years, to be completed by the end of 2005.
      RESULTS: The patients' baseline characteristics confirmed their high-risk status.
      Baseline homocysteine levels varied between countries and regions. HOPE-2 is one
      of the largest trials of folate and vitamins B6 and B12 and is expected to
      significantly contribute to the evaluation of the role of homocysteine lowering
      in CV prevention.

PMID- 16450019
TI  - Myocardial infarction on snow days: incidence, procedure, use and outcomes.
AB  - BACKGROUND: Snowfall can cause chaos in urban centres and put considerable stress
      on health care systems. Given that myocardial infarction (MI) is a condition that
      may be triggered or aggravated by stress, and that health system stress could
      influence the typical care provided to patients with MI, a study was conducted
      comparing 'snow days' with 'nonsnow days', specifically assessing the incidence
      of MI, the use of acute procedures and in-hospital mortality. METHODS: Hospital
      discharge data were used on all patients discharged after MI. These data were
      merged with data from Environment Canada to determine the amount of snowfall that
      occurred on any given day. The use of acute procedures was determined by linking
      to data from the Alberta Provincial PRoject for Outcomes Assessment in Coronary
      Heart disease (APPROACH). Snow days were defined as days when at least 5 cm of
      snow fell, and the two subsequent days were included because of the lingering
      effect of 'urban chaos' that can ensue after significant snowfall. The average
      incidence of MIs on snow days versus nonsnow days was then determined. Risk
      adjusted odds ratios for the use of direct percutaneous coronary intervention and
      in-hospital mortality were also determined. RESULTS: There were 61 snow days and
      575 nonsnow days. The incidence of MI (incidence density ratio of 1.08, 95% CI
      0.82 to 3.10) and the use of direct percutaneous coronary intervention (adjusted
      OR=1.07, 95% CI 0.74 to 1.54) were slightly higher on snow days. In-hospital
      mortality trended toward being lower (adjusted OR=0.54, 95% CI 0.28 to 1.04) for
      patients admitted on snow days, although none of these differences were
      statistically significant. CONCLUSION: Despite the potential for the significant
      adverse effects of snow days on the incidence of MI, the use of acute procedures
      and outcomes, these findings suggest only minor effects, if any.

PMID- 16450018
TI  - Statin wars following coronary revascularization--evidence-based clinical
      practice?
AB  - BACKGROUND: Randomized clinical trials (RCTs) have shown that statins provide
      substantial heath benefits. Pharmaceutical companies spend enormous amounts of
      money on both clinical trials and marketing. The relative influence of
      information from clinical trials on physician prescription patterns for statins
      is unknown. OBJECTIVE: To examine the correlation between statin prescription
      patterns and the quality of evidence from RCTs. METHODS: Using the computerized
      administrative databases of the Quebec Health Insurance Board, the choice of
      statin for elderly patients (older than 65 years of age) following a coronary
      revascularization procedure (percutaneous coronary intervention or coronary
      artery bypass graft surgery) performed between January 1, 1994, and June 30,
      2003, was examined. Prescriptions for each statin were compared with their
      evidence base obtained from a cumulative systematic literature review of RCTs
      that recorded mortality as an outcome and were published before December 31,
      2002. RESULTS: The study cohort comprised 27,979 elderly revascularized patients
      who received at least one statin prescription. In 1996, the year atorvastatin was
      introduced, simvastatin and pravastatin had 38.3% and 37.1% of the market share,
      respectively. By 2003, atorvastatin had 44% of the market share, compared with
      29.9% and 24.1% for simvastatin and pravastatin, respectively. In contrast, RCTs
      published up to the end of 2002 had culminated in 133,341 and 140,565 patient
      years of follow-up for simvastatin and pravastatin, respectively, and only 1459
      patient-years for atorvastatin. CONCLUSIONS: Prescription patterns regarding the
      choice of statin do not appear to be determined uniquely from high-quality RCTs.
      Further research into the other possible determinants of physician prescription
      patterns is necessary.

PMID- 16450016
TI  - Canadian Cardiovascular Society consensus conference recommendations on heart
      failure 2006: diagnosis and management.
AB  - Heart failure remains a common diagnosis, especially in older individuals. It
      continues to be associated with significant morbidity and mortality, but major
      advances in both diagnosis and management have occurred and will continue to
      improve symptoms and other outcomes in patients. The Canadian Cardiovascular
      Society published its first consensus conference recommendations on the diagnosis
      and management of heart failure in 1994, followed by two brief updates, and
      reconvened this consensus conference to provide a comprehensive review of current
      knowledge and management strategies. New clinical trial evidence and meta
      analyses were critically reviewed by a multidisciplinary primary panel who
      developed both recommendations and practical tips, which were reviewed by a
      secondary panel. The resulting document is intended to provide practical advice
      for specialists, family physicians, nurses, pharmacists and others who are
      involved in the care of heart failure patients. Management of heart failure
      begins with an accurate diagnosis, and requires rational combination drug
      therapy, individualization of care for each patient (based on their symptoms,
      clinical presentation and disease severity), appropriate mechanical interventions
      including revascularization and devices, collaborative efforts among health care
      professionals, and education and cooperation of the patient and their immediate
      caregivers. The goal is to translate best evidence-based therapies into clinical
      practice with a measureable impact on the health of heart failure patients in
      Canada.

PMID- 16450020
TI  - The value of lowering blood pressure.
AB  - According to the Canadian Heart Health Survey, only 14% of Canadian hypertensive
      patients are aware of their disease and are treated appropriately. One of the
      reasons for this could be that physicians are confused by an excess of confusing
      and contradictory information regarding the choice of drugs. Two recent
      publications may contribute to a much-needed simplification of the problem. The
      Blood Pressure Lowering Treatment Trialists' Collaboration published a meta
      analysis based on 29 randomized trials that comprised a total of more that
      162,000 participants. The treatment regimens were based on angiotensin-converting
      enzyme inhibitors, angiotensin receptor blockers, diuretics, beta-blockers and
      calcium channel blockers. The main finding of the meta-analysis was that
      treatment with any of the blood pressure-lowering regimens reduced the risk of
      major cardiovascular events, and the extent of these risk reductions was directly
      related to the degree of blood pressure lowering. The Valsartan Antihypertensive
      Long-term Use Evaluation (VALUE) compared valsartan with amlodipine. At the end
      of the study, the reductions in blood pressure from baseline were 17.3/9.9 mmHg
      in the amlodipine group and 15.2/8.2 mmHg in the valsartan group (P<0.0001).
      There was a significantly lower incidence of myocardial infarction in the
      amlodipine group (4.1%) than in the valsartan group (4.8%). From these two
      studies, it would be reasonable to conclude that the treatment of elevated blood
      pressure has two main goals: to achieve a normal blood pressure and to produce a
      happy patient. The agent or agents used to obtain these goals are relatively
      unimportant.

PMID- 16450021
TI  - Incidence, comorbidity, case fatality and readmission of hospitalized stroke
      patients in Canada.
AB  - BACKGROUND: Stroke is a leading cause of death and disability, and poses a
      significant burden of care for those who survive. OBJECTIVES: To estimate the
      incidence of hospitalization for stroke and describe the impact of age, sex and
      comorbidity on in-hospital mortality, length of stay and readmission rates.
      METHODS: Health insurance numbers were used to link acute care hospitalizations
      across Canada in 1999/2000 for stroke patients with no discharges for a stroke
      within the preceding five years. Patients were followed up for one year from the
      date of their initial admission. RESULTS: The numbers of men (15,367) and women
      (16,740) in the study were similar. The incidence of all types of stroke
      (International Classification of Diseases, ninth revision, codes 430, 431 and
      434/436) for hospitalized men and women was 14.4 per 10,000, with a 15-fold rise
      from 8.7 for the age group of 45 to 64 years to 131.9 per 10,000 for the age
      group 80 years and older. For the index episode, stroke patients spent an average
      of 21.0 days in the hospital, and 18.2% died in the hospital within 28 days. Of
      those who survived the first episode, 10.3% were readmitted to the hospital
      within one year with a recurrent stroke, and overall 37.1% were readmitted for
      any cause (including stroke). Among these stroke patients, hypertension was
      codiagnosed in 35%; diabetes in 17%; arrhythmia in 15%; ischemic heart disease in
      13.6%; and congestive heart failure in 5%. CONCLUSIONS: Hospital records linked
      by patient identification can produce more accurate national estimates of
      patients hospitalized with stroke than any current countrywide surveillance
      system.

PMID- 16450022
TI  - Cardiac tamponade in a patient with moderate hemophilia A and factor VIII
      Inhibitors.
AB  - Cardiac tamponade is a rare, life-threatening complication of hemophilia. The
      management of pericardial bleeding in hemophilia A patients with inhibitors is
      particularly challenging because antibodies to factor (F) VIII render the use of
      high-dose FVIII ineffective. Fortunately, the management of uncontrollable
      bleeding in patients with hemophilia and inhibitors has improved since the
      introduction of treatments that bypass the need for FVIII and FIX. A case of
      hemopericardium complicated by cardiac tamponade occurring one month following an
      upper respiratory tract infection in a patient with hemophilia and FVIII
      inhibitors is presented. Management of the present case was based on current
      guidelines on the use of recombinant FVIIa for acute bleeding in patients with
      hemophilia and inhibitors. The subsequent development of hemothorax in the
      present case indicates that a more protracted course of recombinant FVIIa is
      justified following pericardiocentesis for pericardial bleeding in hemophilia
      with inhibitors. Alternative approaches to the management of this complication
      are also reviewed.

PMID- 16450023
TI  - Onset and progression of fatal coronary dissection during angiography.
AB  - Coronary angiography was performed in a 43-year-old man admitted to hospital for
      chest pain. The first frames after the injection of contrast medium showed plaque
      in the left main coronary artery and subtotal stenosis of the mid-left anterior
      descending coronary artery. Dissection of the left main coronary artery appeared,
      with intimal flaps at the proximal segment of the main trunk and the origin of
      the left anterior descending artery. Dissection rapidly progressed into the
      circumflex artery and left anterior descending coronary artery. Although two
      stents were deployed in the left main coronary artery, the patient died of
      ventricular fibrillation.

PMID- 16450024
TI  - Alternating droplet generation and controlled dynamic droplet fusion in
      microfluidic device for CdS nanoparticle synthesis.
AB  - A multifunctional and high-efficiency microfluidic device for droplet generation
      and fusion is presented. Through unique design of the micro-channels, the device
      is able to alternately generate droplets, generating droplet ratios ranging from
      1 ratio 5 to 5 ratio 1, and fuse droplets, enabling precise chemical reactions in
      several picoliters on a single chip. The controlled fusion is managed by passive
      control based on the channel geometry and liquid phase flow. The synthesis of CdS
      nanoparticles utilizing each fused droplet as a microreactor for rapid and
      efficient mixing of reagents is demonstrated in this paper. Following alternating
      droplet generation, the channel geometry allows the exclusive fusion of alternate
      droplets with concomitant rapid mixing and produces supersaturated solution of
      Cd2+ and S2- ions to form CdS nanoparticles in each fused droplet. The
      spectroscopic properties of the CdS nanoparticles produced by this method are
      compared with CdS prepared by bulk mixing.

PMID- 16450025
TI  - A microfluidic flow distributor generating stepwise concentrations for high
      throughput biochemical processing.
AB  - In this paper, we describe a microfluidic device in which solutions with stepwise
      concentrations can be accurately generated by continuously introducing two kinds
      of miscible liquids from each inlet, and biochemical processing can be conducted
      at the various conditions. Introduced liquid flows are geometrically divided into
      a number of downstream flows through multiple distribution channels, and each
      divided flow is then mixed with the divided flow of another liquid at a confluent
      point. The lengths of the precisely designed distribution channels determine the
      mixing ratio of the two liquids, without the influence of flow rate. In this
      study, a PDMS microfluidic device able to generate nine different concentrations
      was fabricated, and the performance of this device was estimated via colorimetric
      assay. As a biological application of this device, cell cultivation was performed
      under different concentration conditions. Due to its simplicity of operation,
      this microfluidic flow distributor will be applied to various kinds of biological
      analysis and screening systems.

PMID- 16450026
TI  - Characterization of the local temperature in space and time around a developing
      Drosophila embryo in a microfluidic device.
AB  - This paper characterizes a microfluidic platform that differentially controls the
      temperature of each half of a living Drosophila melanogaster fruitfly embryo in
      space and time (E. M. Lucchetta, J. H. Lee, L. A. Fu, N. H. Patel and R. F.
      Ismagilov, Nature, 2005, 434, 1134-1138). This platform relies on laminar flow of
      two streams of liquid with different temperature, and on rapid prototyping in
      polydimethylsiloxane (PDMS). Here, we characterized fluid flow and heat transport
      in this platform both experimentally and by numerical simulation, and estimated
      the temperature distribution around and within the embryo by numerical
      simulation, to identify the conditions for creating a sharper temperature
      difference (temperature step) over the embryo. Embryos were removed from the
      device and immunostained histochemically for detection of Paired protein.
      Biochemical processes are sensitive to small differences in environmental
      temperature. The microfluidic platform characterized here could prove useful in
      understanding dynamics of biochemical networks as they respond to changes in
      temperature.

PMID- 16450027
TI  - Microfluidic system for measuring neutrophil migratory responses to fast switches
      of chemical gradients.
AB  - Experimental systems that provide temporal and spatial control of chemical
      gradients are required for probing into the complex mechanisms of eukaryotic cell
      chemotaxis. However, no current technique can simultaneously generate stable
      chemical gradients and allow fast gradient changes. We developed a microfluidic
      system with microstructured membranes for exposing neutrophils to fast and
      precise changes between stable, linear gradients of the known chemoattractant
      Interleukin-8 (IL-8). We observed that rapidly lowering the average concentration
      of IL-8 within a gradient, while preserving the direction of the gradient,
      resulted in temporary neutrophil depolarization. Fast reversal of the gradient
      direction while increasing or decreasing the average concentration also resulted
      in temporary depolarization. Neutrophils adapted and maintained their directional
      motility, only when the average gradient concentration was increased and the
      direction of the gradient preserved. Based on these observations we propose a two
      component temporal sensing mechanism that uses variations of chemokine
      concentration averaged over the entire cell surface and localized at the leading
      edge, respectively, and directs neutrophil responses to changes in their chemical
      microenvironment.

PMID- 16450028
TI  - Droplet-based microfluidics with nonaqueous solvents and solutions.
AB  - In droplet-based ("digital") microfluidics, liquid droplets in contact with
      dielectric surfaces are created, moved, merged and mixed by applying AC or DC
      potentials across electrodes patterned beneath the dielectric. We show for the
      first time that it is possible to manipulate droplets of organic solvents, ionic
      liquids, and aqueous surfactant solutions in air by these mechanisms using only
      modest voltages (<100 V) and frequencies (<10 kHz). The feasibility of moving any
      liquid can be predicted empirically from its frequency-dependent complex
      permittivity, epsilon*. The threshold for droplet actuation in air with our two
      plate device configuration is /epsilon*/>8x10(-11). The mechanistic implications
      of these results are discussed, along with the greatly expanded range of
      applications for digital microfluidics that these results suggest are now
      feasible.

PMID- 16450029
TI  - Mixing with bubbles: a practical technology for use with portable microfluidic
      devices.
AB  - This paper demonstrates a methodology for micromixing that is sufficiently simple
      that it can be used in portable microfluidic devices. It illustrates the use of
      the micromixer by incorporating it into an elementary, portable microfluidic
      system that includes sample introduction, sample filtration, and valving. This
      system has the following characteristics: (i) it is powered with a single hand
      operated source of vacuum, (ii) it allows samples to be loaded easily by
      depositing them into prefabricated wells, (iii) the samples are filtered in situ
      to prevent clogging of the microchannels, (iv) the structure of the channels
      ensure mixing of the laminar streams by interaction with bubbles of gas
      introduced into the channels, (v) the device is prepared in a single-step soft
      lithographic process, and (vi) the device can be prepared to be resistant to the
      adsorption of proteins, and can be used with or without surface-active agents.

PMID- 16450030
TI  - Lab-on-a-chip with integrated optical transducers.
AB  - Taking the next step from individual functional components to higher integrated
      devices, we present a feasibility study of a lab-on-a-chip system with five
      different components monolithically integrated on one substrate. These five
      components represent three main domains of microchip technology: optics, fluidics
      and electronics. In particular, this device includes an on-chip optically pumped
      liquid dye laser, waveguides and fluidic channels with passive diffusive mixers,
      all defined in one layer of SU-8 polymer, as well as embedded photodiodes in the
      silicon substrate. The dye laser emits light at 576 nm, which is directly coupled
      into five waveguides that bring the light to five different locations along a
      fluidic channel for absorbance measurements. The transmitted portion of the light
      is collected at the other side of this cuvette, again by waveguides, and finally
      detected by the photodiodes. Electrical read-out is accomplished by integrated
      metal connectors. To our knowledge, this is the first time that integration of
      all these components has been demonstrated.

PMID- 16450031
TI  - Characterization of a microfluidic dispensing system for localised stimulation of
      cellular networks.
AB  - We present a 3-D microfluidic device designed for localized drug delivery to
      cellular networks. The device features a flow cell comprising a main channel for
      nutrient delivery as well as multiple channels for drug delivery. This device is
      one key component of a larger, fully integrated system now under development,
      based upon a microelectrode array (MEA) with on-chip CMOS circuitry for recording
      and stimulation of electrogenic cells (e.g. neurons, cardiomyocytes). As a
      critical system unit, the microfluidics must be carefully designed and
      characterized to ensure that candidate drugs are delivered to specific regions of
      the culture at known concentrations. Furthermore, microfluidic design and
      functionality is dictated by the size, geometry, and material/electrical
      characteristics of the CMOS MEA. Therefore, this paper reports on the design
      considerations and fabrication of the flow cell, including theoretical and
      experimental analysis of the mass transfer properties of the nutrient and drug
      flows, which are in good agreement with one another. To demonstrate proof of
      concept, the flow cell was mounted on a dummy CMOS chip, which had been plated
      with HL-1 cardiomyocytes. A test chemical compound was delivered to the cell
      culture in a spatially resolved manner. Envisioned applications of this stand
      alone system include simultaneous toxicological testing of multiple compounds and
      chemical stimulation of natural neural networks for neuroscience investigations.

PMID- 16450032
TI  - Demonstration of a PDMS-based bio-microactuator using cultured cardiomyocytes to
      drive polymer micropillars.
AB  - Natural cellular functions are increasingly exploited for integrated chemical
      systems such as biochemical reactors and biosensors. We propose to utilize the
      intrinsic mechanical function of cardiomyocytes, converting chemical energy into
      mechanical energy. In this report, we demonstrate the working principle of our
      proposed poly(dimethylsiloxane) (PDMS) based cardiomyocyte bio-microactuator
      using fabricated PDMS micropillars driven to repetitive motion by attached
      pulsating cardiomyocytes. Sheets of PDMS embedded with an array of micropillars
      were fabricated and modified for cardiomyocyte attachment in culture. Primary
      neonatal rat cardiomyocytes were cultured on the array, attaching to the
      micropillars and substratum successfully, and exhibiting their typical
      spontaneous, pulsatile phenotype. Micropillars beat with the coupled cells
      spontaneously without any triggers. The beat frequency was 1.4 Hz at 37 degrees C
      and the displacement of the top of the pillar that beat most strongly in our
      observation was 2.8+/-0.2 microm. From this result, contractile forces of
      cultured cardiomyocytes were estimated to exceed 3.5 microN. The estimated force
      is far greater than that of a previously described hydrogel-based cardiomyocyte
      bio-microactuator (K. Morishima et al., in Micro Total Analysis Systems 2003, ed.
      M. A. Northrup et al., The Transducers Research Foundation, San Diego, CA, vol.
      2, pp. 1125-1128). PDMS compatibility as a base material for bio-microactuator
      design using cultured cardiomyocytes was verified. This PDMS-based cell
      microactuator worked for about one week without exchange of the culture medium,
      and this system could be developed for various purposes in the future as self
      actuated and efficient mechanochemical transducers without external energy source
      requirements.

PMID- 16450033
TI  - Power-free sequential injection for microchip immunoassay toward point-of-care
      testing.
AB  - This paper presents a simple fluid handling technique for microchip immunoassay.
      Necessary solutions were sequentially injected into a microchannel by air
      evacuated poly(dimethylsiloxane), and were passively regulated by capillary force
      at the inlet opening. For heterogeneous immunoassay, microchips are potentially
      useful for reduction of sample consumption and assay time. However, most of the
      previously reported microchips have limitations in their use because of the needs
      for external power sources for fluid handling. In this paper, an on-chip
      heterogeneous immunofluorescence assay without such an external power source is
      demonstrated. The microchip consisting of poly(dimethylsiloxane) (PDMS) and glass
      has a simple structure, and therefore is suitable for single-use applications.
      Necessary solutions were sequentially injected into a microchannel in an
      autonomous fashion with the power-free pumping technique, which exploits the high
      solubility and the rapid diffusion of air in PDMS. For deionized water, this
      method yielded flow rates of 3-5 nL s-1 with reproducibility of 4-10%. The inlet
      opening of the microchannel functioned as a passive valve to hold the solution
      when the flow was finished. Rabbit immunoglobulin G (rIgG) and human C-reactive
      protein (CRP) were detected using the microchannel walls as reaction sites. With
      the sample consumption of 1 microL and the assay time of approximately 20 min
      including the antibody immobilization step, the sandwich immunoassay methods for
      rIgG and CRP exhibited the limits of detection of 0.21 nM (0.21 fmol) and 0.42 nM
      (0.42 fmol), respectively.

PMID- 16450034
TI  - Recirculating, passive micromixer with a novel sawtooth structure.
AB  - A microfluidic device capable of recirculating nano to microlitre volumes in
      order to efficiently mix solutions is described. The device consists of molded
      polydimethyl siloxane (PDMS) channels with pressure inlet and outlet holes sealed
      by a glass lid. Recirculation is accomplished by a repeatedly reciprocated flow
      over an iterated sawtooth structure. The sawtooth structure serves to change the
      fluid velocity of individual streamlines differently depending on whether the
      fluid is flowing backwards or forward over the structure. Thus, individual
      streamlines can be accelerated or decelerated relative to the other streamlines
      to allow sections of the fluid to interact that would normally be linearly
      separated. Low Reynolds numbers imply that the process is reversible, neglecting
      diffusion. Computer simulations were carried out using FLUENT. Subsequently,
      fluorescent indicators were employed to experimentally verify these numerical
      simulations of the recirculation principal. Finally, mixing of a
      carboxyfluorescein labeled DMSO plug with an unlabeled DMSO plug across an
      immiscible hydrocarbon plug was investigated. At cycling rates of 1 Hz across
      five sawtooth units, the time was recorded to reach steady state in the channels,
      i.e. until both DMSO plugs had the same fluorescence intensity. In the case of
      the sawtooth structures, steady state was reached five times faster than in
      channels without sawtooth structures, which verified what would be expected based
      on numerical simulations. The microfluidic mixer is unique due to its versatility
      with respect to scaling, its potential to also mix solutions containing small
      particles such as beads and cells, and its ease of fabrication and use.

PMID- 16450035
TI  - Paramagnetic particles and mixing in micro-scale flows.
AB  - Mixing in microscale flows with rotating chains of paramagnetic particles can be
      enhanced by adjusting the ratio of viscous to magnetic forces so that chains
      dynamically break and reform. Lattice Boltzmann (LB) simulations were used to
      calculate the interaction between the fluid and suspended paramagnetic particles
      under the influence of a rotating magnetic field. Fluid velocities obtained from
      the LB simulations are used to solve the advection diffusion equation for
      massless tracer particles. At relatively high Mason numbers, small chains result
      in low edge velocities, and hence mixing is slower than at other Mason numbers.
      At low Mason numbers, long, stable chains form and produce little mixing toward
      the center of the chains. A peak in mixing rate is observed when chains break and
      reform. The uniformity of mixing is greater at higher Mason numbers because more
      small chains result in a larger number of small mixing areas.

PMID- 16450036
TI  - Negative pressure pinched sample injection for microchip-based electrophoresis.
AB  - A simple method for injecting well-defined non-biased sample plugs into the
      separation channel of a microfluidic chip-based capillary electrophoresis system
      was developed by a combination of flows generated by negative pressure,
      electrokinetic and hydrostatic forces. This was achieved by using only a single
      syringe pump and a single voltage supply at constant voltage. In the loading
      step, a partial vacuum in the headspace of a sealed sample waste reservoir was
      produced using a syringe pump equipped with a 3-way valve. Almost
      instantaneously, sample was drawn from the sample reservoir across the injection
      intersection to the sample waste reservoir by negative pressure. Simultaneously,
      buffer flow from the remaining two buffer reservoirs pinched the sample flow to
      form a well-defined sample plug at the channel intersection. In the subsequent
      separation stage, the vacuum in headspace of the sample waste reservoir was
      released to terminate all flows generated by negative pressure, and the sample
      plug at the channel intersection was electrokinetically injected into the
      separation channel under the potential applied along the separation channel. The
      liquid levels of the four reservoirs were optimized to prevent sample leakage
      during the separation stage. The approach considerably simplified the operations
      and equipment for pinched injection in chip-based CE, and improved the
      throughput. Migration time precisions of 3.3 and 1.5% RSD for rhodamine123
      (Rh123) and fluorescein sodium (Flu) in the separation of a mixture of Flu and
      Rh123 were obtained for 56 consecutive determinations with peak height precisions
      of 6.2% and 4.4% RSD for Rh123 and Flu, respectively.

PMID- 16450037
TI  - Paramagnetic capture mode magnetophoretic microseparator for high efficiency
      blood cell separations.
AB  - This paper presents the characterization of continuous single-stage and three
      stage cascade paramagnetic capture (PMC) mode magnetophoretic microseparators for
      high efficiency separation of red and white blood cells from diluted whole blood
      based on their native magnetic properties. The separation mechanism for both PMC
      microseparators is based on a high gradient magnetic separation (HGMS) method.
      This approach enables separation of blood cells without the use of additives such
      as magnetic beads. Experimental results for the single-stage PMC microseparator
      show that 91.1% of red blood cells were continuously separated from the sample at
      a volumetric flow rate of 5 microl h-1. In addition, the three-stage cascade PMC
      microseparator continuously separated 93.5% of red blood cells and 97.4% of white
      blood cells from whole blood at a volumetric flow rate of 5 microl h-1.

PMID- 16450038
TI  - DC-dielectrophoretic separation of microparticles using an oil droplet obstacle.
AB  - A new dielectrophoretic particle separation method is demonstrated and examined
      in the following experimental study. Current electrodeless dielectrophoretic
      (DEP) separation techniques utilize insulating solid obstacles in a DC or low
      frequency AC field, while this novel method employs an oil droplet acting as an
      insulating hurdle between two electrodes. When particles move in a non-uniform DC
      field locally formed by the droplet, they are exposed to a negative DEP force
      linearly dependent on their volume, which allows the particle separation by size.
      Since the size of the droplet can be dynamically changed, the electric field
      gradient, and hence DEP force, becomes easily controllable and adjustable to
      various separation parameters. By adjusting the droplet size, particles of three
      different diameter sizes, 1 microm, 5.7 microm and 15.7 microm, were successfully
      separated in a PDMS microfluidic chip, under applied field strength in the range
      from 80 V cm-1 to 240 V cm-1. A very effective separation was realized at the low
      field strength, since the electric field gradient was proved to be a more
      significant parameter for particle discrimination than the applied voltage. By
      utilizing low strength fields and adaptable field gradient, this method can also
      be applied to the separation of biological samples that are generally very
      sensitive to high electric potential.

PMID- 16450039
TI  - AC electroosmotic pump with bubble-free palladium electrodes and rectifying
      polymer membrane valves.
AB  - We present the design, test and theoretical analysis of a novel micropump. The
      purpose is to make a pump with large flow rate (approximately 10 microL min-1)
      and high pressure capacity (approximately 1 bar) powered by a low voltage
      DeltaV<30 V. The pump is operated in AC mode with an electroosmotic actuator in
      connection with a full wave rectifying valve system. Individual valves are based
      on a flexible membrane with a slit. Bubble-free palladium electrodes are
      implemented in order to increase the range of applications and reduce
      maintenance.

PMID- 16450040
TI  - Formation and removal of alkylthiolate self-assembled monolayers on gold in
      aqueous solutions.
AB  - We report the development of novel reagents and approaches for generating
      recyclable biosensors. The use of aqueous media for the formation of protein
      binding alkylthiolate monolayers on Au surfaces results in accelerated
      alkylthiolate monolayer formation and improvement in monolayer integrity as
      visualized by fluorescence microscopy and CV techniques. We have also developed
      an electrocleaning protocol that is compatible with microfluidics devices, and
      this technique serves as an on-chip method for cleaning Au substrates both before
      and after monolayer formation. The techniques for the formation and dissociation
      of biotinylated SAMs from aqueous solvents reported here may be applied towards
      the development of Au-based sensor devices and microfluidics chips in the future.
      A potential use of these devices includes the specific capture and triggered
      release of target cells, proteins, or small molecules from liquid samples.

PMID- 16450041
TI  - A micro-reactor for preparing uniform molecularly imprinted polymer beads.
AB  - In this study, uniform spherical molecularly imprinted polymer beads were
      prepared via controlled suspension polymerization in a spiral-shaped microchannel
      using mineral oil and perfluorocarbon liquid as continuous phases. Monodisperse
      droplets containing the monomers, template, initiator, and porogenic solvent were
      introduced into the microchannel, and particles of uniform size were produced by
      subsequent UV polymerization, quickly and without wasting polymer materials. The
      droplet/particle size was varied by changing the flow conditions in the
      microfluidic device. The diameter of the resulting products typically had a
      coefficient of variation (CV) below 2%. The specific binding sites that were
      created during the imprinting process were analysed via radioligand binding
      analysis. The molecularly imprinted microspheres produced in the liquid
      perfluorocarbon continuous phase had a higher binding capacity compared with the
      particles produced in the mineral oil continuous phase, though it should be noted
      that the aim of this study was not to optimize or maximize imprinting
      performance, but rather to demonstrate broad applicability and compatibility with
      known MIP production methods. The successful imprinting against a model compound
      using two very different continuous phases (one requiring a surfactant to
      stabilize the droplets the other not) demonstrates the generality of this current
      simple approach.

PMID- 16450042
TI  - Fabrication and validation of a multi-channel type microfluidic chip for
      electrokinetic streaming potential devices.
AB  - To elaborate on the applicability of the electrokinetic micro power generation,
      we designed and fabricated the silicon-glass as well as the PDMS-glass
      microfluidic chips with the unique features of a multi-channel. Besides
      miniaturizing the device, the key advantage of our microfluidic chip utilization
      lies in the reduction in water flow rate. Both a distributor and a collector
      taking the tapered duct geometry are positioned aiming the uniform distribution
      of water flow into all individual channels of the chip, in which several hundreds
      of single microchannels are assembled in parallel. A proper methodology is
      developed accompanying the deep reactive ion etching as well as the anodic
      bonding, and optimum process conditions necessary for hard and soft
      micromachining are presented. It has been shown experimentally and theoretically
      that the silicon-based microchannel leads to increasing streaming potential and
      higher external current compared to those of the PDMS-based one. A proper
      comparison between experimental results and theoretical computations allows
      justification of the validity of our novel devices. It is useful to recognize
      that a material inducing a higher magnitude of zeta potential has an advantage
      for obtaining higher power density under the same external resistance.

PMID- 16450043
TI  - Facile fabrication of microfluidic systems using electron beam lithography.
AB  - We present two fast and generic methods for the fabrication of polymeric
      microfluidic systems using electron beam lithography: one that employs spatially
      varying electron-beam energy to expose to different depths a negative electron
      beam resist, and another that employs a spatially varying electron-beam dose to
      differentially expose a bi-layer resist structure. Using these methods, we
      demonstrate the fabrication of various microfluidic unit structures such as
      microchannels of a range of geometries and also other more complex structures
      such as a synthetic gel and a chaotic mixer. These are made without using any
      separate bonding or sacrificial layer patterning and etching steps. The schemes
      are inherently simple and scalable, afford high resolution without compromising
      on speed and allow post CMOS fabrication of microfluidics. We expect them to
      prove very useful for the rapid prototyping of complete integrated
      micro/nanofluidic systems with sense and control electronics fabricated by
      upstream processes.

PMID- 16450044
TI  - The microgenesis of global perception in autism.
AB  - Several studies have reported that individuals with autism and Asperger's
      syndrome show a local processing bias on tasks involving features and
      configurations. This study assessed whether this bias results from differences in
      the perception of features or a cognitive bias to attend to features in autism as
      a consequence of a deficit in attending to configurations. Children with autism
      and typically developing children performed a task assessing the initial
      perceptual representation of features and configurations following a 50 ms
      stimulus display and the development of the perceptual representation by grouping
      processes following an 800 ms stimulus display. No differences were observed
      between the two groups, suggesting that the perceptual and attentional mechanisms
      marshalled by this task operate typically in children with autism.

PMID- 16450046
TI  - Cavernous malformation within a schwannoma: review of the literature and
      hypothesis of a common genetic etiology.
AB  - The finding of cavernous malformations within tumors of the central or peripheral
      nervous system is a rare occurrence. We report a case of a histologically proven
      cavernous malformation found within an eighth cranial nerve schwannoma in a 76
      year-old man. The patient presented with progressive loss of hearing on the left,
      facial pain and dysesthesia. Symptoms improved significantly after the tumor was
      subtotally resected through a left retrosigmoid craniotomy. Including the present
      report, 34 cases of cavernous malformations associated with tumors of nervous
      system origin, 24 cases (71%) involving tumors of Schwann cell origin, and 9
      cases (26%) involving gliomas have been published. The cases were classified into
      two forms based on the type of association. Conjoined association, in which the
      cavernous malformation is located within the tissue of the nervous system tumor,
      and discrete association, in which the cavernous malformation and nervous system
      tumor are in separate locations. We explore the etiology of this association and
      hypothesize that a common genetic pathway may be involved in a majority of these
      cases.

PMID- 16450047
TI  - Yoshihiko Fujita (1932-2005): a pioneer of photoregulation in cyanobacteria.

PMID- 16450045
TI  - The weak coherence account: detail-focused cognitive style in autism spectrum
      disorders.
AB  - "Weak central coherence" refers to the detail-focused processing style proposed
      to characterise autism spectrum disorders (ASD). The original suggestion of a
      core deficit in central processing resulting in failure to extract global
      form/meaning, has been challenged in three ways. First, it may represent an
      outcome of superiority in local processing. Second, it may be a processing bias,
      rather than deficit. Third, weak coherence may occur alongside, rather than
      explain, deficits in social cognition. A review of over 50 empirical studies of
      coherence suggests robust findings of local bias in ASD, with mixed findings
      regarding weak global processing. Local bias appears not to be a mere side-effect
      of executive dysfunction, and may be independent of theory of mind deficits.
      Possible computational and neural models are discussed.

PMID- 16450048
TI  - Effect of altitude on the primary products of photosynthesis and the associated
      enzymes in barley and wheat.
AB  - There is little information available on the primary products of photosynthesis
      and the change in the activity of the associated enzymes with altitude. We
      studied the same in varieties of barley and wheat grown at 1300 (low altitude,
      LA) and 4200 m (high altitude, HA) elevations above mean sea level in the western
      Himalayas. Plants at both the locations had similar photosynthetic rates, leaf
      water potential and the chlorophyll fluorescence kinetics. The short-term radio
      labelling experiments in leaves showed appearance of (14)CO(2) in phosphoglyceric
      acid and sugar phosphates in plants at both the LA and HA, suggesting a major
      role of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in CO(2)
      fixation in the plants at two altitudes, whereas the appearance of labelled
      carbon in aspartate (Asp) and glutamate (Glu) at HA suggested a role of
      phosphoenolpyruvate carboxylase (PEPCase) in photosynthesis metabolism. Plants at
      HA had significantly higher activities of PEPCase, carboxylase and oxygenase
      activity of Rubisco, aspartate aminotransferase (AspAT), and glutamine synthetase
      (GS). However, the activities of malate dehydrogenase, NAD-malic enzyme and
      citrate synthase were similar at the two locations. Such an altered metabolism at
      HA suggested that PEPCase probably captured CO(2) directly from the atmosphere
      and/or that generated metabolically e.g. from photorespiration at HA. Higher
      oxygenase activity at HA suggests high photorespiratory activity. OAA thus
      produced could be additionally channelised for Asp synthesis using Glu as a
      source of ammonia. Higher GS activity ensures higher assimilation rate of NH(3)
      and the synthesis of Glu through GS-GOGAT (glutamine:2-oxoglutarate
      aminotransferase) pathway, also as supported by the appearance of radiolabel in
      Glu at HA. Enhanced PEPCase activity coupled with higher activities of AspAT and
      GS suggests a role in conserving C and N in the HA environment.

PMID- 16450049
TI  - Triplet state spectra and dynamics of geometric isomers of carotenoids.
AB  - The observation of preferential binding of cis-carotenoids in purple bacterial
      photosynthetic reaction centers versus trans-isomers in antenna pigment protein
      complexes has led to the hypothesis that the natural selection of stereoisomers
      has physiological significance. In order to test this hypothesis, we have
      undertaken a systematic series of investigations comparing the optical
      spectroscopic properties and excited state dynamics of cis and trans isomers of
      carotenoids. The present work compares the triplet state spectra, lifetimes, and
      energy transfer rates of all-trans-spheroidene and 13,14-locked-cis-spheroidene,
      the latter of which is incapable of isomerizing to the all-trans configuration,
      and therefore provides a unique opportunity to examine the triplet state
      properties of a structurally stable cis molecule. The data reveal only small
      differences in spectra, decay dynamics, and transfer times and suggest there is
      little intrinsic advantage in either triplet energy transfer or triplet state
      decay arising from the inherently different isomeric forms of cis compared to
      trans carotenoids.

PMID- 16450050
TI  - Excitation energy transfer in the LHC-II trimer: a model based on the new 2.72 A
      structure.
AB  - Energy transfer of the light harvesting complex LHC-II trimer, extracted from
      spinach, was studied in the Q(y) region at room temperature by femtosecond
      transient absorption spectroscopy. Configuration interaction exciton method
      [Linnanto et al. (1999) J Phys Chem B 103: 8739-8750] and 2.72 A structural
      information reported by Liu et al. was used to calculate spectroscopic properties
      and excitation energy transfer rates of the complex. Site energies of the
      pigments and coupling constants of pigment pairs in close contact were calculated
      by using a quantum chemical configuration interaction method. Gaussian random
      variation of the diagonal and off-diagonal exciton matrix elements was used to
      account for inhomogeneous broadening. Rate calculations included only the
      excitonic states initially excited and probed in the experiments. A kinetic model
      was used to simulate time and wavelength dependent absorption changes after
      excitation on the blue side of the Q(y) transition and compared to experimentally
      recorded rates. Analysis of excitonic wavefunctions allowed identification of
      pigments initially excited and probed into later. It was shown that excitation of
      the blue side of the Q(y) band of a single LHC-II complex results in energy
      transfer from chlorophyll b's of the lumenal side to chlorophyll a's located
      primarly on one of the monomers of the stromal side.

PMID- 16450051
TI  - Left- and right-handed LHC II macroaggregates revealed by circularly polarized
      chlorophyll luminescence.
AB  - Circularly polarized chlorophyll luminescence (CPL) may serve as a measure of
      chiral macroaggregates of the light-harvesting chlorophyll-protein complexes (LHC
      II) in both isolated chloroplasts and intact leaves (Gussakovsky et al (2000)
      Photosynth Res 65: 83-92). In the present work, we applied the CPL approach to
      study the effect of fast (1-2 min) thermal impacts on LHC II macroaggregates. The
      results revealed unexpected temperature-response kinetics, composed of initial
      bell-shaped changes in the CPL signal, followed by degradation down to a steady
      state (equilibrium). The bell-shape effect was dependent upon illumination, and
      vanished in the dark. A mathematical analysis of the temperature-response
      kinetics uniquely indicated that LHC II chiral macroaggregates may persist in
      both left- and right-handed forms. These forms differ in their response to high
      temperatures. Both forms are more thermostable in leaves than in isolated
      chloroplasts. The cooperative degradation of LHC II macroaggregates, which is
      induced by the thermal impact, is irreversible. It is therefore suggested that
      the native LHC II macroaggregates are stable, stationary, non-equilibrium,
      spatially heterogeneous (dissipative) structures. The dissipative properties
      probably allow the interconversion between left- and right-handed forms under
      perturbation by certain factors. Illumination probably serves as one such
      perturbation factor, initiating the interconversion of dark-adapted, left-handed
      to light-dependent, right-handed LHC II macroaggregates. The chiral heterogeneity
      of the LHC II macroaggregates is a newly revealed aspect which needs to be taken
      into consideration in future circular dichroism or CPL studies.

PMID- 16450053
TI  - Review: regulation mechanisms of Kinesin-1.
AB  - Kinesin-1 microtubule motors are common kinesin motors from protozoa, fungi and
      animals. They transport vesicular or particle cargo in a strictly regulated
      manner. The relatively well-studied tail inhibition mechanism is based on a
      conformational change that leads to an interaction of Kinesin-1's tail with the
      junction of neck and hinge regions. This folding causes a decrease in microtubule
      binding and motor activity. In fungal Kinesin-1 motors several lines of evidence
      suggest that a conserved tyrosine in the neck coiled-coil mediates this
      inhibition. In the active state, a region surrounding a conserved tryptophan in
      the hinge stabilises the neck coiled-coil, and prevents the tyrosine from
      inhibiting. Although animal and fungal Kinesin-1 motors are clearly homologous
      and function according to the same chemo-mechanical mechanism, they differ in
      their regulation. Unlike fungal Kinesin-1s, animal kinesins associate with light
      chains that are important for regulation and cargo interaction. Several proteins
      interacting with animal Kinesin-1 heavy or light chains are known, among them
      typical scaffolding proteins that seem to link Kinesin-1 to signalling pathways.

PMID- 16450055
TI  - Expression of myostatin RNA transcript and protein in gastrocnemius muscle of
      rats after sciatic nerve resection.
AB  - Myostatin, a member of the transforming growth factor-beta (TGF-beta)
      superfamily, has been identified as an inhibitor of skeletal muscle mass. To have
      an insight into the expression pattern of myostatin and its potential role in
      skeletal muscle atrophy induced by denervation, we used an animal model of
      peripheral nerve resection to examine the time-dependent changes in myostatin
      mRNA and protein levels in the denervated gastrocnemius muscle of rats after
      sciatic neurectomy by the aid of quantitative real-time RT-PCR and Western
      blotting, respectively. We also conducted morphometric analyses to measure the
      wet weight ratio of the denervated muscle (the operated side/contralateral non
      operated side) and the cross sectional area of muscle fibers and to observe
      muscle morphology. The experimental results showed that myostatin mRNA and
      protein levels in rat gastrocnemius muscle persistently elevated after
      denervation, despite a fluctuation of myostatin mRNA level at day 3 after
      denervation, reached their respective peaks at day 28 after denervation, and then
      depressed slightly until day 56 after denervation. Furthermore, a significant
      negative linear correlation was found between myostatin abundance and muscle
      atrophy degree, suggesting that myostatin might probably play an important role
      in denervation-induced muscle atrophy. Our present study perhaps provides a new
      window into myostatin regulation in association with a specific type of muscle
      atrophy.

PMID- 16450054
TI  - Smooth muscle alpha-actinin binds tightly to fesselin and attenuates its activity
      toward actin polymerization.
AB  - Fesselin is an actin binding protein from smooth muscle that nucleates actin
      polymerization in a Ca(++)-calmodulin dependent manner, bundles actin and
      inhibits the actin-activated ATPase activity of myosin S1. We now report that
      fesselin binds to smooth muscle alpha-actinin. Binding was measured by blot
      overlay, affinity chromatography and sedimentation methods. Binding was moderate
      with an association constant of 1-4 x 10(7) M(-1) assuming a 1:1 association of
      fesselin with alpha-actinin. Fesselin binds to the central spectrin domain repeat
      region of alpha-actinin but not to the CH1-CH2 domain. Fesselin accelerates the
      polymerization of actin. This activity of fesselin was attenuated by alpha
      actinin. These observations support the role of fesselin in organizing the
      cytoskeleton.

PMID- 16450056
TI  - The actin-binding cleft: functional characterisation of myosin II with a strut
      mutation.
AB  - The myosin cross-bridge has two essential properties: to undergo the "power
      stroke" and to bind and release from actin - both under control of ATP binding
      and hydrolysis. In the absence of ATP the cross-bridge binds to actin with high
      affinity: the binding of ATP causes rapid release of the cross-bridge from actin.
      The actin binding-site is split by a deep cleft that closes on strong binding to
      actin. The cleft is straddled by a short polypeptide known as the "strut". In the
      following we summarise the structural basis of the power stroke and the control
      of actin affinity and then present data on the effects on actin affinity of
      replacing the strut by a flexible linker.

PMID- 16450057
TI  - Global and local control of microtubule destabilization promoted by a catastrophe
      kinesin MCAK/XKCM1.
AB  - Traditionally, kinesins have been identified as proteins that use the energy of
      ATP to translocate along microtubules. However, in the last decade some kinesin
      like proteins were found to destabilize microtubule ends. The kinesins that
      destabilize microtubules are known as "catastrophe kinesins". Analyses of a
      Xenopus member of the catastrophe kinesins called MCAK/XKCM1 have shown that, in
      fact, catastrophe kinesins are essential for controlling the distribution of
      microtubules by inducing their depolymerization. Therefore, unraveling the
      mechanisms of how microtubule destabilization promoted by these catastrophe
      kinesins is controlled is essential for understanding how microtubules in a cell
      are distributed. Here we give an overview of the studies that have focused on the
      global and local control of microtubule destabilization promoted by MCAK/XKCM1.

PMID- 16450058
TI  - The function of elastic proteins in the oscillatory contraction of insect flight
      muscle.
AB  - Oscillatory contraction of asynchronous insect flight muscle is activated by
      periodic stretches at constant low concentrations of Ca2+. The fibres must be
      relatively stiff to respond to small length changes occurring at high frequency.
      Several proteins in the flight muscle may determine the overall stiffness of the
      fibres. The Drosophila sallimus (sls) gene codes for multiple isoforms with a
      modular structure made up of immunoglobulin (Ig) and elastic PEVK domains, unique
      sequence, and a few fibronectin (Fn) domains at the end of the molecule. Kettin,
      derived from the sls gene, has Ig domains separated by linker sequences and is
      bound to actin near the Z-disc; the C-terminus is associated with the end of the
      A-band. Flight muscle also has longer isoforms of Sls, with extensible PEVK
      sequence, and C-terminal Fn domains; all extend from the Z-disc to the end of the
      A-band. Projectin, from a different gene, has repeating modules of Fn and Ig
      domains, and is associated with the end of thick filaments; tandem Ig and PEVK
      domains at the N-terminus are in the I-band. Projectin, kettin and other Sls
      isoforms form a mechanical link between thick and thin filaments; all are
      probably part of the connecting filaments, which branch from the thick filaments
      and are linked to actin near the Z-disc. The elasticity of fibres may depend on
      the relative amounts of those isoforms with extensible PEVK sequence. Flightin is
      bound on the outside of thick filaments and maintains the stiffness necessary for
      the transmission of stress along the filaments. Insect flight muscle has multiple
      elastic proteins to give the sarcomere the optimum compliance necessary for high
      frequency oscillatory contraction.

PMID- 16450059
TI  - Dimerization of the cardiac ankyrin protein CARP: implications for MARP titin
      based signaling.
AB  - Cardiac ankyrin repeat protein (CARP) and its two close homologs ankrd2 (Arpp)
      and DARP correspond to a conserved gene family of muscle ankyrin repeat proteins
      (MARPs). All three genes respond to a variety of stress/strain injury signals
      with their cytokine-like induction and can associate with the elastic region of
      titin/connectin. Recently, both CARP and ankrd2 were observed to be elevated in
      cardiac diseases as well as muscular dystrophies, implicating their joined
      signaling in muscle diseases. Here we show that CARP in the yeast two-hybrid
      system (YTH) interacts with itself and desmin. To further verify the YTH data and
      to investigate possible CARP subunit structure(s), we expressed CARP in E. coli.
      Expressed CARP has an apparent mobility of about 70 kDa on gel filtration,
      corresponding to a dimeric species. Yeast two-hybrid experiments using amino- and
      carboxyterminal deletion clones suggest that CARP, ankrd2, and DARP contain
      potential coiled-coil dimerization motifs within their unique aminoterminal
      domains that mediate the formation of homo-dimers. In contrast, we could not
      detect the formation of hetero-dimers between CARP, ankrd2, and DARP. Therefore,
      when CARP, ankrd2 and DARP are upregulated in disease/stress states, they are
      likely to be sorted into distinct structural protein complexes since CARP within
      the MARP family contains a unique aminoterminal dimerization motif.

PMID- 16450060
TI  - Anomalous drainage of the inferior vena cava into the left atrium.

PMID- 16450061
TI  - Partial pericardial defect with left atrial herniation.

PMID- 16450062
TI  - Can cystinosis cause coronary artery dilatation?
AB  - In children, dilated coronary arteries are usually caused by Kawasaki's disease.
      We report four children with dilated coronary arteries and nephropathic
      cystinosis.

PMID- 16450063
TI  - The first finding of a Rickettsia bacterium associated with parthenogenesis
      induction among insects.
AB  - The larval endoparasitoid, Neochrysocharis formosa (Westwood), is an important
      natural enemy of the leafminer Liriomyza trifolii (Burgess) in Japan. The
      thelytokous strain of N. formosa mostly produces female progeny. Male progeny
      were produced by females treated with tetracycline, suggesting that
      microorganisms induce thelytoky in N. formosa. The result of nucleotide
      sequencing of the 16S rRNA gene indicated that the parasitoid is infected with a
      Rickettsia bacterium, which appears to be causative of the thelytoky. Although
      Rickettsia-bellii-like bacteria have been found to be associated with various
      reproductive disorders, this is the first finding of a parthenogenesis-inducing
      Rickettsia among insects.

PMID- 16450064
TI  - Biochemical characterization of a beta-1,3-glucanase from Trichoderma koningii
      induced by cell wall of Rhizoctonia solani.
AB  - Trichoderma species are readily isolated from Brazilian cerrado soil by
      conventional methods and some of them were characterized as Trichoderma koningii.
      The effect of carbon source on the production of beta-1,3-glucanases in the
      culture filtrates of a specific Trichoderma koningii strain (ALL 13) was
      investigated. Enzyme activity was detected in all carbon sources tested and only
      one band of beta-1,3-glucanase was detected in non-denaturing PAGE. This enzyme
      was purified by Sephacryl S-200 gel filtration and Phenyl Sepharose CL 4B
      chromatography. A typical procedure provided 105-fold purification with 13.4%
      yield. The molecular weight of the purified enzyme was 75 kDa as estimated by SDS
      PAGE. The enzyme hydrolyzed laminarin in an endo-like fashion to form small
      oligosaccharides and glucose. The Km and Vmax values for beta-1,3-glucanase,
      using laminarin as substrate, were 0.148 mg.mL-1 and 0.159 U.min-1, respectively.
      The pH optimum for the enzyme was pH 4.6 and maximum activity was obtained at 50
      degrees C. Hg2+ inhibited the purified enzyme.

PMID- 16450065
TI  - Isolation and characterization of a cold-active xylanase enzyme from
      Flavobacterium sp.
AB  - Xylan is the major component of hemicellulose, and xylan should be fully utilized
      to improve the efficiencies of a biobased economy. There are a variety of
      industrial reaction conditions in which an active xylanase enzyme would be
      desired. As a result, xylanase enzymes with different activity profiles are of
      great interest. We isolated a xylanase gene (xyn10) from a Flavobacterium sp.
      whose sequence suggests that it is a glycosyl hydrolase family 10 member. The
      enzyme has a temperature optimum of 30 degrees C, is active at cold temperatures,
      and is thermolabile. The enzyme has an apparent Km of 1.8 mg/ml and kcat of 100
      sec-1 for beechwood xylan, attacks highly branched native xylan substrates, and
      does not have activity against glucans.

PMID- 16450066
TI  - Differential predation by Bdellovibrio bacteriovorus 109J.
AB  - Bdellovibrio bacteriovorus is a predatory bacterium that can replicate only
      inside Gram-negative bacteria. We incubated B. bacteriovorus 109J in a mixture of
      two prey cells present in equal numbers and enumerated prey cells after 3 h of
      predation. In multiple prey pairings, B. bacteriovorus preferentially lysed on
      one prey over the other. When prey were individually incubated with B.
      bacteriovorus, they were preyed on with different efficiencies. Three prey had
      only 5-8% of cells remaining after Bdellovibrio predation and the other three
      prey had 37-43% of cells remaining. Timing of attachment of B. bacteriovorus to
      prey cells also varied with Bdellovibrio attachment to more preferred prey
      occurring the fastest. These results suggest that B. bacteriovorus 109J does not
      randomly infect prey cells but infects and kills some prey more readily than
      others.

PMID- 16450068
TI  - Fuzzy logic control of bioreactor for enhanced biosynthesis of alkaline protease
      by an alkalophilic strain of Bacillus subtilis.
AB  - Present studies describe the optimization of some cultural parameters such as
      medium pH, incubation temperature, and agitation rate for the biosynthesis of
      alkaline protease by Bacillus subtilis IH-72 in a bioreactor using fuzzy logic
      control. The process of fermentation was carried out in a 7.5-L bioreactor (New
      Brunswick Scientific, USA) with a working volume of 5 L. All of the parameters
      were automatically controlled with the help of attached software. The optimum pH,
      temperature, and agitation for the production of alkaline protease by B. subtilis
      IH-72 were found to be 9.0, 35 degrees C, and 175 rpm, respectively. The
      performance of the fuzzy logic of the bioreactor was found to be encouraging for
      enhanced production of the enzymes. The maximum production of alkaline protease
      during the present study was found to be 9.6 U mL-1.

PMID- 16450067
TI  - Bacteroides fragilis group: trends in resistance.
AB  - Representing the major part of the human colon microflora, members of the
      Bacteroides fragilis group are frequently involved in mixed aerobic and anaerobic
      infections. Recent studies show an increased resistance of the B. fragilis group
      against several antimicrobial agents. The aim of the present study was to
      determine the susceptibility of 87 B. fragilis group strains isolated in
      2003/2004 in Western Austria against eight antimicrobial agents by Etest.
      Furthermore, the resistance patterns were compared with those of 45 B. fragilis
      group strains isolated in 1992 and referred to the world wide trend towards
      increased resistance. In 1992 as well as in 2003/2004, all strains were
      susceptible against metronidazole and imipenem. However, comparing the MIC-values
      of the B. fragilis group strains collected 1992 with data from 2003/2004, a
      significant increase in resistance was found for clindamycin (p<0.01). Regarding
      cefoxitin, a similar trend could be observed. However, this difference was not
      yet significant (p=0.144). Our findings underline the emerging resistance of the
      B. fragilis group against antimicrobial agents and underscore the importance of
      susceptibility testing of anaerobes even in routine laboratories.

PMID- 16450069
TI  - Versatile expression and secretion vectors for Bacillus subtilis.
AB  - Most expression systems are based on Escherichia coli as the host strain because
      of the large availability of all kinds of vector plasmids. However, aside from
      the obvious advantages of E. coli systems, serious problems can occur during the
      process of heterologous gene expression and purification. Therefore, low
      expression rates, formation of inclusion bodies, improper protein-folding, and/or
      toxicity problems might enforce changing the expression host. Here we describe
      the construction of two new vectors, pBSMuL1 and pBSMuL2, for overexpression and
      secretion of heterologous proteins in Bacillus subtilis as an alternative
      expression host. The new plasmids combine several advantages in comparison to
      available Bacillus expression systems: an appropriate multiple cloning site
      consisting of 13 unique restriction sites, one (pBSMuL1) or two (pBSMuL2) strong
      constitutive promoters, a high efficient signal sequence for protein secretion,
      and the possibility to express proteins as His-tagged fusions for easy detection
      and purification. We have demonstrated the applicability of the novel vector
      plasmids for the production and purification of the heterologous cutinase from
      Fusarium solani pisi.

PMID- 16450070
TI  - Mycobacterium avium genes upregulated upon infection of Acanthamoeba castellanii
      demonstrate a common response to the intracellular environment.
AB  - Using a previously created Mycobacterium avium genomic library with GFP-promoter
      trap in Mycobacterium smegmatis, we screened for genes that are upregulated upon
      infection of A. castellanii. Clones exhibiting a 2.5-fold or greater increase in
      GFP expression, out of a total of 10,000 clones, were selected for further
      examination. Upregulation was confirmed in subsequent experiments. A total of 20
      clones showed an increase in expression 24 and 48 h after infection. Homologues
      were identified, and genes were found to encode for a variety of functions,
      including metabolic pathways, protein transcription and translation, and
      macromolecule degradation. Eight out of the 20 genes were found to be the same as
      those upregulated upon human macrophage infection. Five genes were selected to
      confirm upregulation in M. avium following amoeba infection, using real time PCR.
      All 5 genes were found to be upregulated at least 2.5-fold in M. avium. These
      results showed that the GFP promoter library in M. smegmatis is a valid system
      for studying gene upregulation in M. avium systems, and that many M. avium genes
      are commonly upregulated following macrophage and amoeba infection.

PMID- 16450071
TI  - Cloning and characterization of a fur homologue from Azospirillum brasilense Sp7.
AB  - A homologue of the ferric uptake regulator gene, fur, was identified from a
      Azospirillum brasilense Sp7 genomic DNA clone. Experiments performed with
      transcriptional lacZ fusions demonstrated that the A. brasilense fur homologue
      regulated the expression of two fur regulated Escherichia coli genes: fiu (ferric
      iron uptake) and fhuF (ferric hydroxamate uptake). A differential regulation by
      the cognate Fur and the heterologous Fur homologue in response to the iron status
      of the growth medium was also observed.

PMID- 16450073
TI  - Isolation and identification of natural endophytic rhizobia from rice (Oryza
      sativa L.) through rDNA PCR-RFLP and sequence analysis.
AB  - Three novel endophytic rhizobial strains (RRE3, RRE5, and RRE6) were isolated
      from naturally growing surface sterilized rice roots. These isolates had the
      ability to nodulate common bean (Phaseolus vulgaris). Polymerase chain reaction
      restriction fragment length polymorphism and sequencing of 16S rDNA of these
      isolates revealed that RRE3 and RRE5 are phylogenetically very close to
      Burkholderia cepacia complex, whereas RRE6 has affinity with Rhizobium
      leguminosarum bv. phaseoli. Plant infection test using gusA reporter gene tagged
      construct of these isolates indicated that bacterial cells can go inside and
      colonize the rice root interiors. A significant increase in biomass and grain
      yield was also recorded in greenhouse-grown rice plants inoculated with these
      isolates.

PMID- 16450072
TI  - Fluoroquinolone resistance linked to both gyrA and parC mutations in the
      quinolone resistance-determining region of Shigella dysenteriae type 1.
AB  - We examined the quinolone resistance-determining region (QRDR) of gyrA, gyrB, and
      parC of recently isolated fluoroquinolone-resistant S. dysenteriae type 1 strains
      from south Asia and compared data with fluoroquinolone-susceptible strains
      associated with previous epidemics of 1978, 1984, and 1994. In fluoroquinolone
      resistant strains, double mutations (Ser83-->Leu, Asp87-->Asn or Gly) and a
      single mutation (Ser80-->Ile) were detected in the QRDRs of gyrA and parC,
      respectively.

PMID- 16450074
TI  - Ischemic preconditioning depends on age and gender.
AB  - The goal of this study was to determine if an ischemic preconditioning (IPC)
      protocol improved post-ischemic functional recovery of female mouse hearts. A
      previous study found that IPC did not occur in hearts from 10-week-old females.
      We studied Langendorff-perfused hearts from both 10- and 18-week-old mice (males
      and females). Hearts were subjected to 45 min ischemia and 45 reperfusion (I/R);
      IPC involved pretreatment with 3 min ischemia. We measured hemodynamics, infarct
      size and levels of the phosphorylated prosurvival kinase Akt (p-Akt). Similar to
      a previous study, for 10- week-old mice we found that the IPC protocol
      appreciably improved recovery of LV developed pressure (LVDP) for hearts from
      males but not females. However, for 18-week-old mice we found that the IPC
      protocol doubled the recovery of LVDP for both males and females. For both ages,
      hearts from females had greater recovery of LVDP and higher levels of p-Akt
      compared to males. CONCLUSIONS: These findings are consistent with growing
      evidence that preconditioning induced by ischemia or other interventions can
      occur in hearts from females. However, for hearts from females, preconditioning
      depends on age. Moreover, consistent with previous studies, hearts from females
      have greater inherent resistance to ischemic injury, possibly involving increased
      signaling via p-Akt.

PMID- 16450075
TI  - Post-conditioning induced cardioprotection requires signaling through a redox
      sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C
      activation.
AB  - Post-conditioning (Post-C) induced cardioprotection involves activation of
      guanylyl-cyclase. In the ischemic preconditioning scenario, the downstream
      targets of cGMP include mitochondrial ATP-sensitive K(+) (mK(ATP)) channels and
      protein kinase C (PKC), which involve reactive oxygen species (ROS) production.
      This study tests the hypothesis that mK(ATP), PKC and ROS are also involved in
      the Post-C protection. Isolated rat hearts underwent 30 min global ischemia (I)
      and 120 min reperfusion (R) with or without Post-C (i.e., 5 cycles of 10 s R/I
      immediately after the 30 min ischemia). In 6 groups (3 with and 3 without Post-C)
      either mK(ATP) channel blocker, 5- hydroxydecanoate (5-HD), or PKC inhibitor,
      chelerythrine (CHE) or ROS scavenger, N-acetyl-cysteine (NAC), were given during
      the entire reperfusion (120 min). In other 6 groups (3 with and 3 without Post
      C), 5-HD, CHE or NAC were infused for 117 min only starting after 3 min of
      reperfusion not to interfere with the early effects of Post-C and/or reperfusion.
      In an additional group NAC was given during Post-C maneuvers (i.e., 3 min only).
      Myocardial damage was evaluated using nitro-blue tetrazolium staining and lactate
      dehydrogenase (LDH) release. Post-C attenuated myocardial infarct size (21 +/- 3%
      vs. 64 +/- 5% in control; p < 0.01). Such an effect was abolished by 5-HD or CHE
      given during either the 120 or 117 min of reperfusion as well as by NAC given
      during the 120 min or the initial 3 min of reperfusion. However, delayed NAC
      (i.e., 117 min infusion) did not alter the protective effect of Post- C (infarct
      size 32 +/- 5%; p < 0.01 vs. control, NS vs. Post-C). CHE, 5-HD or NAC given in
      the absence of Post-C did not alter the effects of I/R. Similar results were
      obtained in terms of LDH release. Our data show that Post-C induced protection
      involves an early redox-sensitive mechanism as well as a persistent activation of
      mK(ATP) and PKC, suggesting that the mK(ATP)/ROS/PKC pathway is involved in post
      conditioning.

PMID- 16450076
TI  - Potentiated response to adrenomedullin in myocardia and aortas in spontaneously
      hypertensive rat.
AB  - Adrenomedullin (AM) is a multifunctional regulatory peptide, and endogenous AM is
      an important factor in regulating cardiovascular and renal homeostasis as a
      potent cardio-reno-protective factor. To illustrate the protective mechanism of
      adrenomedullin (AM) on the cardiovascular system by observing (1) the changes in
      mRNA and protein levels of AM and its receptor-calcitonin receptor-like receptor
      (CL) and receptor activity-modifying proteins (RAMPs)-in myocardia and aortas of
      spontaneously hypertensive rats (SHRs) and (2) the response of cardiovascular
      tissue to AM. The AM content and cyclic adenosine monophosphate (cAMP) production
      in myocardia and aortas were measured in SHRs and Wistar Kyoto (WKY) rats (11
      week-old) by radioimmunoassay (RIA). The mRNA levels of brain natriuretic peptide
      (BNP), AM, CL, RAMP1, -2, -3 were determined by semi-quantitative RTPCR. Protein
      levels of CL, RAMP1, -2, -3 were assayed by Western blotting. SHRs had severe
      hypertension, and the tail-blood pressure was 76.7% higher, the ratio of heart
      weight to body weight (heart coefficient) 45.5% higher, and the BNP gene
      expression 4.5-fold higher than that of WKY rats (all p < 0.01). The AM-ir
      content in plasma, myocardia and aortas of SHRs increased by 42.5%, 68.3% and
      80.4%, respectively (all p < 0.01) compared with WKY rats. Furthermore, the mRNA
      levels of AM, CL, RAMP1, RAMP2 and RAMP3 were elevated by 46% (p < 0.01), 62% (p
      < 0.05), 51.2% (p < 0.01), 41% (p < 0.01) and 54% (p < 0.01), respectively, in
      myocardia and by 72%, 87%, 155%, 53% and 74% (all p < 0.01), respectively, in
      aortas. The elevated mRNA level of CL, RAMP1 RAMP2 and RAMP3 correlated
      positively with that of AM mRNA in hypertrophic myocardia (r= 0.943, 0.621, 0.688
      and 0.633, respectively, all p < 0.01) and aortas (r = 0.762, 0.892, 0.828 and
      0.736, respectively, all p < 0.01). The protein levels of CL, RAMP1, RAMP2 and
      RAMP3 in myocardia and aortas of SHRs were increased compared with that of WKY
      rats. The response to AM was potentiated in myocardia and aortas in SHRs, and the
      production of cAMP was increased by 47% and 65% (both p < 0.01), respectively. AM
      stimulated cAMP generation in myocardia and aortas was blocked by both AM(22-52),
      the specific antagonist of AM, and calcitonin gene-related peptide (CGRP)(8-37),
      the antagonist of the CGRP1 receptor. In myocardia and aortas of SHRs, the gene
      expressions and protein levels of AM, CL, RAMP1, RAMP2 and RAMP3 were increased,
      and the response to AM was potentiated. AM-stimulated cAMP generation in
      myocardia and aortas was blocked by both AM(22-52) and CGRP(8-37). The results
      suggest that the changes of AM and its receptors in cardiovascular tissue, and
      the increased response of cardiovascular tissue to AM might importantly impact
      the pathogenesis of hypertension.

PMID- 16450077
TI  - The antiatherogenic and antiinflammatory effect of HDL-associated
      lysosphingolipids operates via Akt -->NF-kappaB signalling pathways in human
      vascular endothelial cells.
AB  - Adhesion of mononuclear cells to the vascular endothelium and their subsequent
      transmigration into the arterial wall represent key events in the pathogenesis of
      arteriosclerosis. In previous studies we have shown that high density
      lipoproteins (HDL) and the HDL-associated sphingosylphosphorylcholine (SPC) have
      the ability to suppress the TNF-alpha-induced expression of endothelial cell E
      selectin. However, the current understanding of the mechanism by which HDL
      reduces the expression of E-selectin is still incomplete. In the present study we
      show that interaction of the HDL-associated sphingosylphosphorylcholine and
      sphingosylgalactosyl-3-sulfate (lysosulfatide, LSF) with the G-protein-coupled
      EDG receptor initiates a signalling cascade that activates the protein kinase Akt
      and reduces the E-selectin, ICAM-1 and VCAM-1 expression on protein and mRNA
      level. This signalling cascade is consistently associated with a reduced
      translocation of TNF-alpha-activated NF-kappaB into the cell nucleus. The
      suppressor effect of SPC and LSF is completely reverted by inhibition of the
      phosphatidylinositol- 3-kinase/Akt pathway. We conclude that the
      antiatherogenic/antiinflammatory effect of lysosphingolipids depends on a
      competitive interaction of EDG receptor-induced inhibition and TNF-alpha
      initiated stimulation of NF-kappaB translocation into the cell nucleus thereby
      preventing or stimulating inflammatory events in atherogenesis.

PMID- 16450078
TI  - One year results of a randomised controlled multi-centre study comparing Prolene
      and Vypro II-mesh in Lichtenstein hernioplasty.
AB  - A standard polypropylene mesh used in Lichtenstein's operation induces a strong
      foreign tissue reaction with potential harmful effects. A mesh with less
      polypropylene could possibly be beneficial. Six hundred men with primary
      unilateral inguinal hernias were randomised to Lichtenstein's operation using a
      Prolene- or Vypro II-mesh in six centres. The patients were blinded to which mesh
      they received. A validated questionnaire assessing recurrence and pain along with
      SF-36 Health Survey was sent after 1 year to all patients and a selected group
      was clinically examined. Of the 591 operated patients, 526 (89.0%) returned the
      questionnaire. 188 patients had some complaints or sensations of which 111
      patients were clinically examined. The mean follow-up time was 13.6 (SD. 4.0)
      months. The incidence of hernia recurrence (four vs. four patients) and neuralgia
      (three vs. four patients) did not differ between Prolene and Vypro II-groups,
      respectively. One Vypro II-patient was re-operated due to neuralgia. There was no
      difference in the SF-36 scores. The results of Lichtenstein's operation with
      either Prolene or Vypro II do not seem to differ significantly.

PMID- 16450079
TI  - Deepithelialization of a complex ventral hernia for completely extraperitoneal
      Rives-Stoppa herniorrhaphy.
AB  - Peritoneal incisions made during abdominal surgery are associated with numerous
      postoperative complications. Laparoscopic procedures are extraperitoneal, but
      they do not always provide adequate exposure of the defect nor room for
      manipulation. We suggest a de-epithelialization approach prior to mesh placement
      for the repair of large ventral hernias as a means of achieving a completely
      extraperitoneal ventral herniorrhaphy.

PMID- 16450080
TI  - Bochdalek's hernia in an adult with colon necrosis.
AB  - The improper fusion of the posterolateral foramina of the diaphragm was first
      described by Bochdalek in 1848. The true incidence of this congenital anomaly
      ranges from 1/7,000 to 6%. Although it is a well-known neonatal disease, it can
      also be diagnosed incidentally in adult patients. Until now, a total of around
      100 cases of occult asymptomatic Bochdalek's hernia have been reported. The
      symptomatic cases are encountered more rarely. Colon necrosis among the
      symptomatic cases was reported in some cases. We herein report a case of a 21
      year-old man with a left-sided Bochdalek's hernia which led to total necrosis of
      the transverse colon. Following resection and colocolonic anastomosis, the defect
      on the diaphragm was repaired. After an uneventful recovery period, he was
      discharged from the hospital on the 10th postoperative day. Being aware of this
      rarely encountered disease and of the factors for early diagnosis is of utmost
      importance to decrease mortality and morbidity.

PMID- 16450082
TI  - Essential host plant cues in the grapevine moth.
AB  - Host plant odours attract gravid insect females for oviposition. The
      identification of these plant volatile compounds is essential for our
      understanding of plant-insect relationships and contributes to plant breeding for
      improved resistance against insects. Chemical analysis of grape headspace and
      subsequent behavioural studies in the wind tunnel show that host finding in
      grapevine moth Lobesia botrana is encoded by a ratio-specific blend of three
      ubiquitous plant volatiles. The odour signal that attracts mated females to grape
      consists of the terpenoids (E)-beta-caryophyllene, (E)-beta-farnesene and (E)-4,8
      dimethyl-1,3,7-nonatriene. These compounds represent only a fraction of the
      volatiles released by grapes, and they are widespread compounds known throughout
      the plant kingdom. Specificity may be achieved by the blend ratio, which was
      100:78:9 in grape headspace. This blend elicited anemotactic behaviour in moths
      at remarkably small amounts. Females were attracted at release rates of only a
      few nanograms per minute, at levels nearly as low as those known for the
      attraction of male moths to the female sex pheromones.

PMID- 16450081
TI  - Epiploic appendicitis in inguinal hernia sac presenting an inguinal mass.
AB  - Inguinal hernia sometimes surprises surgeons with its unexpected content.
      Epiploic appendagitis in hernia sac is a very rare entity. We report a 60-year
      old male patient with a painless inguinal mass. Surgical exploration showed a 4
      cm mass beneath the external oblique aponeurosis that consisted of a hernia sac
      containing an inflamed and remarkably swollen appendix epiploica of the sigmoid
      colon secondary to torsion. The patient recovered after the resection of epiploic
      appendix and a tension-free hernia repair.

PMID- 16450083
TI  - Judging where a ball will go: the case of curved free kicks in football.
AB  - This study examined whether adding spin to a ball in the free kick situation in
      football affects a professional footballer's perception of the ball's future
      arrival position. Using a virtual reality set-up, participants observed the
      flight paths of aerodynamically realistic free kicks with (+/-600 rpm) and
      without sidespin. With the viewpoint being fixed in the centre of the goal,
      participants had to judge whether the ball would have ended up in the goal or
      not. Results show that trajectories influenced by the Magnus force caused by
      sidespin gave rise to a significant shift in the percentage of goal responses.
      The resulting acceleration that causes the ball to continually change its heading
      direction as the trajectory unfolds does not seem to be taken into account by the
      participants when making goal judgments. We conclude that the visual system is
      not attuned to such accelerated motion, which may explain why goalkeepers appear
      to misjudge the future arrival point of such curved free kicks.

PMID- 16450084
TI  - Tumor staging using whole-body high-resolution 16-channel PET-CT: does additional
      low-dose chest CT in inspiration improve the detection of solitary pulmonary
      nodules?
AB  - For optimal image fusion between CT and F-18-FDG-PET, the acquisition of CT
      images is performed in mild expiratory suspension, which might compromise the
      detection of lung metastases. This study aimed at evaluating the influence of
      expiration on the detection of solitary pulmonary nodules (SPN) and at assessing
      if additional inspiratory low-dose CT (I-LDCT) of the chest can improve the
      detection of potential lung metastases performing whole-body 16-channel PET-CT.
      Sixty-six patients with malignant tumors underwent PET-CT: contrast-enhanced CT
      was acquired during mild expiration and was used for fusion with PET images;
      additionally, chest I-LDCT was performed at deep inspiration. Two radiologists
      reported all SPN detected at I-LDCT and the expiratory CT scan independently.
      Overall, 53% of 128 SPN (mean: 3.8+/-0.2 mm) were detected at both respiratory
      states: 51 SPN only at I-LDCT, and 9 nodules only at expiratory CT. Of the SPN,
      117/128 were classified as certain; 45 of those were additionally detected at I
      LDCT, and 6 nodules at expiratory CT. A 100% detection rate was reached in SPN >4
      mm at I-LDCT versus >8 mm at expiratory CT (all P<0.001). Additional I-LDCT of
      the chest significantly improves the detection of SPN at whole-body F-18-FDG-PET
      CT and thus is recommended as part of the standard protocol for oncological
      patients.

PMID- 16450085
TI  - [Update on the pathomorphological assessment of vasculopathies in pulmonary
      arterial hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a term which has recently been redefined
      and includes idiopathic pulmonary arterial hypertension, familial pulmonary
      arterial hypertension PAH related to specific pathological conditions (e.g.
      connective tissue diseases), as well as PAH caused by veno-occlusive disease or
      capillary hemangiomatosis. The clinical manifestation seems to be related to a
      peculiar pathological anatomy involving small, muscular pulmonary arteries,
      capillaries and veins. In addition to common hypertrophy of the tunica media,
      other vascular compartments may also be affected by intimal thickening or
      adventitial fibrosis. Moreover, complex lesions, such as so called plexiform
      lesions and arteritis can be present in certain forms of the disease. While the
      recent identification of responsible gene mutations in subgroups of patients have
      shed some light on disease evolution, therapeutic strategies must currently rely
      on vasodilative and antimitogenic drugs acting on the intimal and medial level of
      the affected pulmonary vessels. The clinical outcome of patients suffering from
      PAH remains poor, underlining our need for a better comprehension of disease
      pathophysiology, and thus for the characterization of specific histomorphological
      patterns.

PMID- 16450086
TI  - Combined data from two phase III trials of the NK1 antagonist aprepitant plus a
      5HT 3 antagonist and a corticosteroid for prevention of chemotherapy-induced
      nausea and vomiting: effect of gender on treatment response.
AB  - GOALS OF WORK: Prevention of chemotherapy-induced nausea and vomiting (CINV) with
      standard antiemetics has been more difficult to achieve in female patients. Data
      from two phase III trials of the NK1 antagonist aprepitant were assessed for
      potential effect of gender on treatment response. PATIENTS AND METHODS: 1,044
      patients receiving cisplatin (> or = 70 mg/m2) were randomly assigned to control
      regimen [ondansetron (O) 32 mg i.v. and dexamethasone (D) 20 mg p.o. on day 1; D
      8 mg twice daily on days 2-4] or aprepitant (A) regimen (A 125 mg p.o. plus O 32
      mg and D 12 mg on day 1; A 80 mg and D 8 mg once daily on days 2-3; and D 8 mg on
      day 4). The primary endpoint was overall complete response (no emesis and no
      rescue therapy over days 1-5). Data were analyzed by a modified intent-to-treat
      approach. Between-treatment comparisons for each gender were made using logistic
      regression. MAIN RESULTS: Women comprised 42 and 43% of the aprepitant and
      control groups, respectively. In the control group, 41% of women had overall
      complete response compared with 53% of men. In the aprepitant group, 66% of women
      had overall complete response compared with 69% of men. CONCLUSION: The addition
      of aprepitant may negate the adverse prognostic effect of female gender on the
      prevention of CINV in patients receiving highly emetogenic chemotherapy.

PMID- 16450087
TI  - Bisphosphonates for malignancy-related bone disease: current status, future
      developments.
AB  - This review relates to the efficacy and safety of bisphosphonates in metastatic
      bone disease. It discusses practical recommendations and possible future
      indications for bisphosphonate therapy. The current aims of bisphosphonates for
      metastatic bone disease are to prevent skeletal-related events (SREs), reduce
      bone pain and improve quality of life. Phase III clinical trials of clodronate
      and pamidronate have established their efficacy against bone complications in
      patients with breast cancer and multiple myeloma, while randomized trials have
      shown SRE reductions with zoledronic acid in patients with breast cancer and
      multiple myeloma, prostate cancer, and lung and other solid tumors. These
      bisphosphonates also have some effect on metastatic bone pain. Ibandronate is a
      new aminobisphosphonate, available in more than 40 countries outside of the US as
      intravenous and oral formulations for the prevention of skeletal events in
      patients with breast cancer and bone metastases. Phase III studies have shown
      that both intravenously and orally administered ibandronate have efficacy for the
      prevention of skeletal events and for the reduction of metastatic bone pain. In
      addition to efficacy, the long-term tolerability of bisphosphonates in metastatic
      bone disease influences drug selection. Besides their use in patients with
      established bone metastases, recent and ongoing research suggests that
      bisphosphonates also have clinical benefit in the adjuvant setting, and for the
      treatment of cancer-treatment-induced bone loss. Such interesting new
      developments may underpin a new era of bisphosphonate use sometime in the near
      future.

PMID- 16450088
TI  - Development and evaluation of an audiovisual information resource to promote self
      management of chemotherapy side-effects.
AB  - Based on a theoretical framework, we developed an audiovisual resource to promote
      self-management of eight common chemotherapy side-effects. A patient needs
      analysis identified content domains, best evidence for preparing patients for
      threatening medical procedures and a systematic review of effective self-care
      strategies informed script content. Patients and health professionals were
      invited to complete a written evaluation of the video. A 25-min video was
      produced. Fifty health professionals and 37 patients completed the evaluation.
      All considered the video informative and easy to understand. The majority
      believed the video would reduce anxiety and help patients prepare for
      chemotherapy. Underpinned by a robust theoretical framework, we have developed an
      evidence-based resource that is perceived by both patients and health
      professionals as likely to enhance preparedness for chemotherapy.

PMID- 16450089
TI  - N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant
      chemotherapy in colon cancer patients: preliminary data.
AB  - Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant
      chemotherapy for colon cancer may improve disease-free survival, grade 3-4
      sensory neuropathy also increases. To determine whether oral N-acetylcysteine is
      neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study.
      Fourteen stage III colon cancer patients with 4 or more regional lymph nodes
      metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m(2)) plus
      weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N
      acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and
      electrophysiological evaluations were performed at baseline and after 4, 8, and
      12 treatment cycles. Treatment-related toxicity was evaluated based on National
      Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine
      patients in arm B and two of five in arm A experienced grade 1 sensory
      neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2-4
      toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2-4 sensory
      neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There
      were no significant electrophysiological changes in arm A after 4, 8, or 12
      cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the
      incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving
      oxaliplatin-based adjuvant chemotherapy.

PMID- 16450090
TI  - Preterm birth and later insulin resistance: effects of birth weight and postnatal
      growth in a population based longitudinal study from birth into adult life.
AB  - AIMS/HYPOTHESIS: An increased risk of type 2 diabetes mellitus is associated with
      low birthweight after full-term gestation, including amplification of this risk
      by weight gain during infancy and adult body composition. Premature birth is also
      associated with insulin resistance, but studies conducted so far have not
      provided follow-up into adulthood. We studied the effects of (1) lower
      birthweight (as standard deviation score [SDS]) and infancy weight gain on
      insulin resistance in 19-year-olds born before 32 weeks of gestation, and (2) the
      interaction between lower birthweight SDS and infancy weight gain, as well as
      between lower birthweight and adult body composition, on insulin resistance.
      METHODS: This was a prospective follow-up study in 346 subjects from the Project
      on Preterm and Small-for-gestational-age infants cohort, in whom fasting glucose,
      insulin and C-peptide levels were measured at 19 years. Insulin resistance was
      calculated with homeostatic modelling (homeostatic model assessment for insulin
      resistance index [HOMA-IR]). RESULTS: Birthweight SDS was unrelated to the
      outcomes. Rapid infancy weight gain until 3 months post-term was weakly
      associated with higher insulin level (p=0.05). Adult fatness was positively
      associated with insulin and C-peptide levels and HOMA-IR (all p<0.001). On these
      parameters, there was a statistical interaction between birthweight SDS and adult
      fat mass (p=0.002 to 0.03). CONCLUSIONS/INTERPRETATION: In subjects born very
      preterm, rapid infancy weight gain until 3 months predicted higher insulin levels
      at 19 years, but the association was weak. Adult obesity strongly predicted
      higher insulin and C-peptide levels as well as HOMA-IR. The effect of adult fat
      mass on these parameters was dependent on its interaction with birthweight SDS.

PMID- 16450091
TI  - Comment to: Patti ME, McMahon G, Mun EC et al. (2005) Severe hypoglycaemia post
      gastric bypass requiring partial pancreatectomy: evidence for inappropriate
      insulin secretion and pancreatic islet hyperplasia. Diabetologia 48:2236-2240.

PMID- 16450092
TI  - Searching for the etiology of systemic inflammatory response syndrome: is SIRS
      occult endotoxemia?

PMID- 16450093
TI  - Transcutaneous arterial carbon dioxide pressure monitoring in critically ill
      adult patients.
AB  - OBJECTIVE: To evaluate the accuracy of transcutaneous PCO(2) (PtcCO(2)) as a
      surrogate for arterial PCO(2) (PaCO(2)) in a cohort of adult critically ill
      patients in a medical intensive care unit (ICU). DESIGN: Prospective
      observational study comparing paired measures of transcutaneous and arterial
      PCO(2). SETTING: A 26-bed medical ICU. PATIENTS: Fifty ICU patients monitored
      with a SenTec Digital Monitor placed at the ear lobe over prolonged periods.
      RESULTS: A total of 189 paired PCO(2) measures were obtained. Twenty-one were
      excluded from analysis, because profound skin vasoconstriction was present
      (PCO(2) bias =-10.8+/-21.8 mmHg). Finally, 168 were analysed, including 137
      obtained during mechanical ventilation and 82 under catecholamine treatment. Body
      temperature was below 36 degrees C for 27 measurements. Mean duration of
      monitoring was 17+/-17 h. The mean difference between PaCO(2) and PtcCO(2) was 
      0.2+/-4.6 mmHg with a tight correlation (R(2)=0.92, p>0.01). PCO(2) bias did not
      significantly change among three successive measurements. Changes in PaCO(2) and
      in PtcCO(2) between two blood samples were well correlated (R(2)=0.78, p>0.01).
      Variations of more than 8 mmHg in PtcCO(2) had 86% sensitivity and 80%
      specificity to correctly predict similar changes in PaCO(2) in the same
      direction. Catecholamine dose or respiratory support did not affect PtcCO(2)
      accuracy. Hypothermia has only a small effect on accuracy. No complication
      related to a prolonged use of the sensor was observed CONCLUSION: Transcutaneous
      PCO(2) provides a safe and reliable trend-monitoring tool, provided there is no
      major vasoconstriction.

PMID- 16450094
TI  - Dramatic beneficial effects of sildenafil in recurrent massive pulmonary
      embolism.
AB  - OBJECTIVE: Sildenafil has a well established pulmonary vasodilatory effect, but
      has seldom been used in critically ill patients. We report a case of severe
      recurrent pulmonary embolism in which sildenafil was used as a rescue therapy.
      RESULTS: After oral administration of 50 mg of sildenafil, cardiac index
      increased from 2.11/min/m(2) to 3.21/min/m(2); mean pulmonary artery pressure
      decreased from 56 mmHg to 46 mmHg, and pulmonary vascular resistance index
      decreased from 700 dynes/cm(-5)/m(2) to 425 dynes/cm(-5)/m(2), without reduction
      of arterial systemic pressure. Clinical condition also improved during the
      following days under treatment of 50 mg sildenafil three times daily.
      CONCLUSIONS: These observations should stimulate studies with sildenafil in the
      ICU setting. Sildenafil is easy to administer in every ICU and at any time. If
      its potential is confirmed, it may be a life-saving drug in some emergency
      situations caused by severe pulmonary hypertension.

PMID- 16450096
TI  - Comment on: "Nosocomial viral ventilator-associated pneumonia in the intensive
      care unit" by Daubin et al.

PMID- 16450097
TI  - Effects of neuromuscular block on systemic and cerebral hemodynamics and
      bispectral index during moderate or deep sedation in critically ill patients.
AB  - OBJECTIVE: To investigate whether neuromuscular block can affect bispectral index
      (BIS) or cerebral hemodynamics under moderate or deep sedation produced by
      propofol. DESIGN AND SETTING: Prospective, controlled study in a university
      hospital affiliated intensive care unit. PATIENTS: Seventeen surgical patients
      undergoing elective esophagectomy. INTERVENTIONS: After stabilization with either
      light or deep sedation we investigated whether the BIS, electromyographic
      activity (EMG), or cerebral and systemic hemodynamic parameters were affected by
      administration of muscle relaxant. MEASUREMENTS AND MAIN RESULTS: Neuromuscular
      block reduced the BIS during moderate sedation but not during deep sedation
      although the EMG at both levels of sedation was significantly reduced. No
      positive effects of neuromuscular block on cerebral hemodynamics were obtained
      with monitoring of regional cerebral oxygen saturation and middle cerebral artery
      blood velocity; however, significant effects on systemic hemodynamic parameters
      were observed only at moderate propofol sedation. The values of BIS and systemic
      hemodynamic variables with moderate sedation were also very similar to those with
      deep sedation and neuromuscular block although these values differed without
      neuromuscular block. CONCLUSIONS: Neuromuscular block altered the BIS score in
      moderately sedated patients but not in deeply sedated patients although cerebral
      hemodynamics was not affected by neuromuscular block during either moderate or
      deep sedation. Muscular relaxant also enhanced cardiovascular stability with
      moderate sedation. These results suggest that level of consciousness may be
      decreased by neuromuscular block during moderate sedation but not affected during
      deep sedation.

PMID- 16450099
TI  - Jaundice in critical illness: promoting factors of a concealed reality.
AB  - OBJECTIVE: In critical illness, liver dysfunction (LD) is associated with a poor
      outcome independently of other organ dysfunctions. Since strategies to support
      liver function are not available, a timely and accurate identification of factors
      promoting LD may lead to prevention or attenuation of its consequences. The aim
      of this study was to assess risk factors for LD in critically ill patients.
      DESIGN: Prospective, observational study. SETTING: A multidisciplinary intensive
      care unit (ICU) of a university hospital. PATIENTS: All patients consecutively
      admitted over a 6-month period. INTERVENTION: None. MEASUREMENTS AND RESULTS: LD
      was defined as serum bilirubin levels >or=2 mg/dl and lasting for at least 48 h.
      Out of 283 patients, 141 matched inclusion criteria. Forty-four patients (31.2%)
      showed LD (LD group), while 97 (68.8%) were included in control group (C group).
      A binomial analysis showed that LD occurrence was associated with moderate (odds
      ratio [OR] 3.11; p=0.04) and severe shock (OR 3.46; p= 0.05), sepsis (OR 3.03;
      p=0.04), PEEP ventilation (OR 4.25; p=0.006), major surgery (OR 4.03; p=0.03),
      and gram-negative infections (OR 3.94; p=0.002). In stepwise multivariate
      analysis, the single independent predictive factors of LD resulted in severe
      shock (p=0.002), sepsis (p=0.03), PEEP ventilation (p=0.04), and major surgery
      (p=0.05). CONCLUSIONS: In critically ill patients jaundice is common, and severe
      shock states, sepsis, mechanical ventilation with PEEP and major surgery are
      critical risk factors for its onset. Since there is no specific treatment, prompt
      resuscitation, treatment of sepsis and meticulous supportive care will likely
      reduce its incidence and severity.

PMID- 16450098
TI  - Year in review in intensive care medicine. 2005. I. Acute respiratory failure and
      acute lung injury, ventilation, hemodynamics, education, renal failure.

PMID- 16450100
TI  - Endotoxin immunity and the development of the systemic inflammatory response
      syndrome in critically ill children.
AB  - BACKGROUND: The systemic inflammatory response syndrome (SIRS) may be triggered
      by endotoxin. Humans have antibodies directed against the core of endotoxin
      (endotoxin core antibodies, EndoCAb) that appear to be protective following
      surgery and in sepsis. We hypothesised that children with elevated antibodies to
      endotoxin core would be less likely to develop SIRS in their initial period on
      intensive care. Because of the existing literature we defined two sub-groups
      according to the primary reason for ICU admission: infection and non-infection.
      METHODS: We recruited 139 consecutive patients admitted to a paediatric intensive
      care unit (PICU) with more than one organ failure for longer than 12 h as part of
      another study. Patients were classified on admission to PICU as having an
      infectious or a non-infections diagnosis. The occurrence of SIRS within 48 h of
      admission was recorded along with detailed clinical and demographic data, EndoCAb
      concentration and the potential confounding variables C-reactive protein and
      mannose-binding lectin. RESULTS: In the 71 patients admitted without infection
      (primarily post-operative and head injured) IgG EndoCAb was significantly lower
      in patients who developed SIRS than those who did not (72 vs. 131 MU/ml),
      independent of potential confounding variables. In patients with infection there
      was no significant difference in IgG EndoCAb between children developing SIRS and
      those who did not (111 vs. 80 MU/ml). CONCLUSION: Head injured and post-operative
      patients admitted to PICU who develop early SIRS have significantly lower serum
      IgG EndoCAb levels than those who do not.

PMID- 16450101
TI  - Soluble form of the triggering receptor expressed on myeloid cells 1: an anti
      inflammatory mediator?

PMID- 16450103
TI  - Ultrasonographic examination of the venae cavae.

PMID- 16450104
TI  - Rickettsia slovaca in Dermacentor ticks found on humans in Spain.

PMID- 16450102
TI  - Soluble triggering receptor expressed on myeloid cells 1 as an anti-inflammatory
      mediator in sepsis.
AB  - OBJECTIVE: To define the significance of soluble triggering receptor expressed on
      myeloid cells 1 (sTREM-1) in the septic cascade by comparing its kinetics to
      those of other proinflammatory mediators and of interleukin (IL) 10. DESIGN:
      Prospective study in a tertiary unit. PATIENTS: Blood was sampled from 90
      patients with septic syndrome due to ventilator-associated pneumonia for 7 days
      after the appearance of symptoms. Concentrations of tumor necrosis factor (TNF)
      alpha, IL-6, IL-8, IL-10, and sTREM-1 were determined by enzyme-linked
      immunosorbent assay. RESULTS: Serum levels of TNFalpha, IL-6, IL-10, and sTREM-1
      were higher in nonsurvivors than in survivors; similar differences were not found
      for IL-8. Positive correlations were found between the ratios IL-10/TNFalpha and
      sTREM-1/TNFalpha, between IL-10/IL-6 and sTREM-1/IL-6, and between IL-10/IL-8 and
      sTREM-1/IL-8. Median values of IL-10/TNFalpha upon presentation of sepsis, severe
      sepsis, and septic shock were 3.21, 2.16, and 2.86, respectively (NS). Respective
      values for sTREM-1/TNFalpha were 21.28, 7.33, and 27.78 (p=0.047 between sepsis
      and severe sepsis, p=0.003 between severe sepsis and septic shock). CONCLUSIONS:
      sTREM-1 follows the kinetics of IL-10 and should therefore be considered an anti
      inflammatory mediator in sepsis. Decreased ratios of sTREM-1/TNFalpha might
      determine transition from sepsis to severe sepsis and from severe sepsis to
      septic shock.

PMID- 16450105
TI  - Predictive control of grip force when moving object with an elastic load applied
      on the arm.
AB  - Skilled object manipulation relies on the capability to adjust the grip force
      according to the consequences of our movements in terms of the resulting load
      force of the object. Such predictive grip force control requires (at least) two
      neural processes: (1) predicting the kinematic characteristics of the unfolding
      arm trajectory and (2) predicting the load force on the object resulting, among
      other factors, from the arm movement. The goal of this study was to examine
      whether subjects can still anticipate the resulting load force on the object when
      the moving arm is submitted to a type of load that does not contribute to the
      object load. To this end, 12 subjects were asked to rhythmically move a 0.4 kg
      object under three different conditions. In the first condition (ARM), an elastic
      cord was attached to the upper arm. In the second condition, the elastic cord was
      attached to the object (OBJECT). In the third condition, the elastic cord was
      absent (NO ELAST). At the kinematic level, results showed no influence of the
      elastic cord on the pattern of movement of the object. At the kinetic level,
      cross-correlation analyses between grip force and load force acting on the object
      revealed significant correlations with minimal delays. In addition, grip force
      profiles were similar under the ARM and NO ELAST conditions, both differing from
      the OBJECT condition. Overall, we interpret these results as evidence that the
      neural processes involved in the prediction of the arm trajectory and those
      involved in the prediction of the load on the object held can take into account
      different external force fields, thereby preserving the functionality of the
      behaviour.

PMID- 16450107
TI  - Tissue responses to an experimental calcium phosphate cement and mineral trioxide
      aggregate as materials for furcation perforation repair: a histological study in
      dogs.
AB  - The aim was to evaluate histologically the inflammatory reactions and tissue
      responses to an experimental tricalcium phosphate cement (TCP) and mineral
      trioxide aggregate (MTA) when used as repair materials in furcation perforations
      in dogs. Perforations were performed in 24 mandibular premolars of six
      anaesthetised dogs and filled either with ProRoot MTA (grey) or TCP. The root
      canals were subsequently shaped and filled, and the access cavities were closed
      with a bonded composite resin. The animals were killed at 12 weeks. After
      radiological examination, the teeth and surrounding structures were processed for
      light microscopy. Concerning the grades of inflammation, MTA exhibited
      significantly better results than TCP (chi-square test according to Pearson). No
      furcation was free of inflammatory cells. Mild inflammation was observed in nine
      of twelve cases with MTA and only twice in those with TCP. No significant
      differences were revealed between MTA and TCP in terms of bone reorganization or
      deposition of fibrous connective tissue (Mantel-Haenszel chi-square test). The
      grade of radiological examination corresponded with the grade of inflammation or
      differed by only one grade plus or minus. Perforations located in the furcation
      of teeth remain an endodontic and a periodontal problem with an uncertain
      prognosis, in spite of the promising modern materials applied.

PMID- 16450109
TI  - Selection and optimization of proteolytically stable llama single-domain antibody
      fragments for oral immunotherapy.
AB  - We previously demonstrated that oral application of the recombinant single-domain
      antibody fragment (VHH) clone K609, directed against Escherichia coli F4
      fimbriae, reduced E. coli-induced diarrhoea in piglets, but only at high VHH
      doses. We have now shown that a large portion of the orally applied K609 VHH is
      proteolytically degraded in the stomach. Stringent selection for proteolytic
      stability identified seven VHHs with 7- to 138-fold increased stability after in
      vitro incubation in gastric fluid. By DNA shuffling we obtained four clones with
      a further 1.5- to 3-fold increased in vitro stability. These VHHs differed by at
      most ten amino acid residues from each other and K609 that were scattered over
      the VHH sequence and did not overlap with predicted protease cleavage sites. The
      most stable clone, K922, retained 41% activity after incubation in gastric fluid
      and 90% in jejunal fluid. Oral application of K922 to piglets confirmed its
      improved proteolytic stability. In addition, K922 bound to F4 fimbriae with
      higher affinity and inhibited fimbrial adhesion at lower VHH concentrations. K922
      is thus a promising candidate for prevention of piglet diarrhoea. Furthermore,
      our findings could guide selection and improvement by genetic engineering of
      other recombinant antibody fragments for oral use.

PMID- 16450108
TI  - Does irradiation affect the protein composition of saliva?
AB  - The purpose of this study was to compare the relative amount of low molecular
      weight salivary proteins in patients with head and neck tumours treated with
      radiotherapy and healthy subjects. Reverse-phase high-pressure liquid
      chromatography was used for protein separation. Nine protein fractions (including
      acidic and basic proline-rich proteins (PRPs), cystatins, histatins and
      statherin) were identified in saliva from irradiated patients as well as healthy
      subjects. However, compared with non-irradiated healthy subjects, the fraction of
      acidic PRPs was significantly reduced in irradiated patients. These data indicate
      an alteration of the relative amount of low molecular weight salivary proteins in
      irradiated patients besides the reduction of salivary flow.

PMID- 16450110
TI  - The utilization of sugar cane molasses with/without the presence of
      lignosulfonate for the production of bacterial cellulose.
AB  - Production of bacterial cellulose (BC) using sugar cane molasses (MO)
      with/without the presence of lignosulfonate (MOL) as a sole carbon source in a
      Hestrin-Schramm medium (HS) was investigated. Six strains of Acetobacter xylinum
      [American Type Culture Collection 10245 and Institute of Fermentation in Osaka
      (IFO) 13693, 13772, 13773, 14815, and 15237] were screened for their BC
      production. The yield of the BC among all the strains from both the MO and MOL
      media was much higher than that from the HS medium. Acetobacter xylinum IFO 13772
      was the best BC producer for all media. Furthermore, physical properties of these
      BC from the HS, MO, and MOL media were studied using Fourier-transform infrared
      spectroscopy, X-ray diffractometer, and cross polarization/magic angle spinning
      13C nuclear magnetic resonance. There are no significant differences in the
      crystallinity and the recorded Ialpha fraction among the BC produced from the
      different media. A remarkable difference was only recorded in terms of viscosity.
      These results indicate that MO is a better carbon source than glucose for most of
      the strains investigated.

PMID- 16450111
TI  - The complete DNA sequence of the mitochondrial genome of the dermatophyte fungus
      Epidermophyton floccosum.
AB  - We report here the complete nucleotide sequence of the 30.9-kb mitochondrial
      genome of the dermatophyte fungus Epidermophyton floccosum. All genes are encoded
      on the same DNA strand and include seven subunits of the reduced nicotinamide
      adenine dinucleotide ubiquinone oxireductase (nad1, nad2, nad3, nad4, nad4L,
      nad5, and nad6), three subunits of cytochrome oxidase (cox1, cox2, and cox3),
      apocytochrome b (cob), three subunits of ATP synthase (atp6, atp8, and atp9), the
      small and large ribosomal RNAs (rns and rnl), and 25 tRNAs. A ribosomal protein
      gene (rps5) is present as an intronic ORF in the large ribosomal subunit. The
      genes coding for cob and cox1 carry one intron and nad5 carries two introns with
      ORFs. The mtDNA of E. floccosum has the same gene order as Trichophyton rubrum
      mtDNA, with the exception of some tRNA genes. Maximum likelihood phylogenetic
      analysis confirms T. rubrum as a close relative of E. floccosum. This is the
      first complete mitochondrial sequence of a species of the order Onygenales. This
      sequence is available under GenBank accession number AY916130.

PMID- 16450112
TI  - Structural insights into the effect of isonucleosides on B-DNA duplexes using
      molecular-dynamics simulations.
AB  - Some structural insights into the conformations of the isonucleosides containing
      duplexes have been provided. Unrestrained molecular-dynamics simulations on 18
      mer duplexes with isonucleosides incorporated at the 3'-end or in the center of
      one strand have been carried out with explicit solvent under periodic boundary
      conditions using the AMBER force field and the particle mesh Ewald method. The
      Watson-Crick hydrogen-bonding patterns of the duplexes studied remained intact
      throughout the simulation. For the modified duplexes, the changes observed in the
      inter-base pair parameters and backbone torsional angles were primarily localized
      at the isonucleoside-inserted area. All five structures studied remained in the B
      form family. The decreased stacking abilities indicated by the large changes in
      inter-base pair parameters and the large changes in backbones made the modified
      duplexes show a minor thermal destabilization in comparison with native DNA. The
      MM_PBSA method for estimating binding free energies on two complementary strands
      was used. The results showed that the binding free energies of isonucleoside
      incorporated DNA duplexes were lower than the native DNA duplex, which is in good
      agreement with experimental observations.

PMID- 16450113
TI  - Effect of fouling on the capacity and breakthrough characteristics of a packed
      bed ion exchange chromatography column.
AB  - This study examined the impact of fouling with yeast homogenate on capacity and
      breakthrough performance of an ion exchange packed bed column. Column performance
      was assessed by analysis of breakthrough curves obtained with BSA as a test
      protein. The overall impact of fouling on breakthrough performance depended
      heavily on the level of clarification of the feed stream. Challenging the column
      with particulate-free homogenate caused no change in column performance. Loading
      successive small volumes of poorly clarified homogenate, interspersed with
      frequent column salt washes, did not alter significantly the column capacity. By
      contrast, when the column was challenged with an equivalent cumulative volume of
      poorly clarified homogenate, dynamic binding capacity decreased significantly and
      changes in breakthrough curves suggested increased intraparticle and external
      mass transfer limitations. These changes were ascribed to deposition of solid
      particulates in void spaces in the bed and colloidal contaminants in the bead
      pores.

PMID- 16450114
TI  - Further clarification of the contribution of the tryptophan hydroxylase (TPH)
      gene to suicidal behavior using systematic allelic and genotypic meta-analyses.
AB  - Suicide is a major public health issue, especially in western countries,
      accounting for approximately 1 million deaths every year throughout the world.
      The tryptophan hydroxylase (TPH) gene has been extensively studied as a candidate
      for suicidal behavior due to its role in serotonergic neurotransmission. Since
      the first study associating the gene with schizophrenia, there have been many
      attempts to replicate it. However, a number of these studies have produced
      contrary results, possibly reflecting inadequate statistical power and the use of
      different populations. Association data relating European and, more particularly,
      Asian populations has become increasingly available in recent years. To examine
      whether the aggregate data provide evidence of statistical significance, the
      current meta-analysis has combined all the published studies up to July 2005, and
      examined the polymorphisms (A779C, A218C, A-6526G) in the context of varied
      suicidal behaviors by analyzing the studies in total and in subsets. Compared
      with the inconsistent results of previous studies, the current results (22
      references) confirm a strong overall association between suicidal behavior and
      the A779C/A218C polymorphisms, supporting the involvement of TPH in the
      pathogenesis of suicidal behavior.

PMID- 16450115
TI  - Alterations of calf venous and arterial compliance following acclimation to heat
      administered at a fixed daily time in humans.
AB  - We investigated the effects of heat acclimation on venous and arterial compliance
      in humans. Four male and four female volunteers were exposed to an ambient
      temperature of 40 degrees C and relative humidity of 40% for 4 h (1330-1730
      hours) per day for 9-10 consecutive days. The calf venous compliance (CV) was
      estimated using venous occlusion plethysmography with a mercury-in-silastic
      strain gauge placed around the right calf at its maximum girth. The compliance of
      the small (CSA) and large (CLA) arteries were assessed by reflective and
      capacitance compliance by analyzing the radial artery blood pressure waveforms,
      basing on the use of a modified Windkessel model. The calf CV, CSA, CLA, systolic
      and diastolic blood pressures, heart rate and core temperature were determined
      twice a day, 0930-1100 hours (AM test) and 1500-1630 hours (PM test), in both
      heat-acclimated and non-heat-acclimated (control) conditions. Heat acclimation
      appeared to decrease blood pressures, heart rate and significantly lowered core
      temperature only in the PM test. In the control condition, the calf CV was not
      affected by the time of day and the CSA was significantly depressed in the PM
      test. After acclimation to heat, the calf CV significantly increased and the CSA
      did not decrease in the PM test. The results presented suggest that repeated heat
      exposure in humans, for 4 h at a fixed time daily, increases the calf CV and the
      CSA particularly during the period when the subjects were previously exposed to
      heat.

PMID- 16450116
TI  - Active tactile sensing for localization of objects by the cockroach antenna.
AB  - Antennal movement during tactile orientation behavior was examined three
      dimensionally in American cockroaches during tethered walking. When a wooden rod
      was presented to the tip of one antenna in an upright orientation at one of the
      three different horizontal positions (30 degrees , 60 degrees , or 90 degrees
      from the center of the head), the animal touched it repeatedly with the antenna,
      and tried to approach it (positive thigmotaxis). Positional shifts were also
      observed for the contralateral unstimulated antenna. The ipsilateral antenna
      tended to touch the object during inward movement (adduction) at all three test
      angles. The cumulative turn angle made during a continuous test period of 24 s
      clearly depended on the object's position; however, the contact frequencies were
      almost the same regardless of the position. The relationships between contact
      frequency and some locomotion parameters were also investigated on a shorter time
      scale of 3 s. The contact frequency positively correlated with the turn angle,
      with the accuracy of orientation at all three test angles, and with the
      translation velocity at test angles of 30 degrees and 60 degrees . It is
      concluded that the performance during tactile orientation can be represented
      effectively by the frequency with which the antennae touch the attractive
      objects.

PMID- 16450117
TI  - Specializations in the lumbosacral vertebral canal and spinal cord of birds:
      evidence of a function as a sense organ which is involved in the control of
      walking.
AB  - Birds are bipedal animals with a center of gravity rostral to the insertion of
      the hindlimbs. This imposes special demands on keeping balance when moving on the
      ground. Recently, specializations in the lumbosacral region have been suggested
      to function as a sense organ of equilibrium which is involved in the control of
      walking. Morphological, electrophysiological, behavioral and embryological
      evidence for such a function is reviewed. Birds have two nearly independent kinds
      of locomotion and it is suggested that two different sense organs play an
      important role in their respective control: the vestibular organ during flight
      and the lumbosacral system during walking.

PMID- 16450120
TI  - Oncocytic adenocarcinoma of the rectum arising on a villous adenoma with
      oncocytic features.
AB  - Rectal adenocarcinoma with diffuse oncocytic features is a very rare lesion,
      having been reported only once in the English literature. We describe a case of
      oncocytic adenocarcinoma of the rectum, associated with a villous adenoma,
      arising on a 66-year-old man. On histological examination, the adenocarcinoma was
      composed of neoplastic glands lined by a strongly eosinophilic, granular
      epithelium that deeply infiltrated the rectal wall. Some basophilic
      calcifications were present in the gland lumina. Superficially, a villous adenoma
      with high-grade dysplasia was evident; adenomatous cells showed focal
      eosinophilic changes, consisting of a large granular cytoplasm, an oval atypical
      nucleus, and a prominent nucleolus. Immunohistochemically, neoplastic glands
      reacted strongly with antimitochondria antibody, carcinoembryonic antigen,
      cytokeratin 20, p53, and CDX2. Molecular alterations observed in oncocytic
      changes and their significance with regards to neoplastic transformation are
      briefly discussed.

PMID- 16450118
TI  - Encoding and processing biologically relevant temporal information in
      electrosensory systems.
AB  - Wave-type weakly electric fish are specialists in time-domain processing:
      behaviors in these animals are often tightly correlated with the temporal
      structure of electrosensory signals. Behavioral responses in these fish can be
      dependent on differences in the temporal structure of electrosensory signals
      alone. This feature has facilitated the study of temporal codes and processing in
      central nervous system circuits of these animals. The temporal encoding and
      mechanisms used to transform temporal codes in the brain have been identified and
      characterized in several species, including South American gymnotid species and
      in the African mormyrid genus Gymnarchus. These distantly related groups use
      similar strategies for neural computations of information on the order of
      microseconds, milliseconds, and seconds. Here, we describe a suite of mechanisms
      for behaviorally relevant computations of temporal information that have been
      elucidated in these systems. These results show the critical role that behavioral
      experiments continue to have in the study of the neural control of behavior and
      its evolution.

PMID- 16450119
TI  - Interruption of pacemaker signals by a diencephalic nucleus in the African
      electric fish, Gymnarchus niloticus.
AB  - The African electric fish Gymnarchus niloticus rhythmically emits electric organ
      discharges (EODs) for communication and navigation. The EODs are generated by the
      electric organ in the tail in response to the command signals from the medullary
      pacemaker complex, which consists of a pacemaker nucleus (PN), two lateral relay
      nuclei (LRN) and a medial relay nucleus (MRN). The premotor structure and its
      modulatory influences on the pacemaker complex have been investigated in this
      paper. A bilateral prepacemaker nucleus (PPn) was found in the area of the dorsal
      posterior nucleus (DP) of the thalamus by retrograde labeling from the PN. No
      retrogradely labeled neurons outside the pacemaker complex were found after
      tracer injection into the LRN or MRN. Accordingly, anterogradely labeled terminal
      fibers from PPn neurons were found only in the PN. Iontophoresis of L-glutamate
      into the region of the PPn induced EOD interruptions. Despite the exclusive
      projection of the PPn neurons to the PN, extracellular and intracellular
      recordings showed that PN neurons continue their firing while MRN neurons ceased
      their firing during EOD interruption. This mode of EOD interruption differs from
      those found in any other weakly electric fishes in which EOD cessation mechanisms
      have been known.

PMID- 16450122
TI  - In vitro assays for adhesion and migration of osteoblastic cells (Saos-2) on
      titanium surfaces.
AB  - The first event occurring at the boundary between a metal implant and living
      tissue is the attachment of cells onto the metal surface of the implant. The
      attachment characteristics of the metal in this situation are critical in
      determining its biocompatibility and usefulness as artificial bone and tooth
      implants. Using the human osteosarcoma cell line Saos-2, we attempted to
      establish simple and reliable methods for evaluating the attachment of cultured
      osteoblastic cells onto titanium samples that had been subjected to various
      surface treatments. Fluorescence actin imaging showed that cells cultured on
      titanium with hydrofluoric acid etching (HF-Ti) exhibited delayed spreading of
      their cytoplasm, as compared to cells cultured for the same length of time on
      nitrided titanium or physically polished titanium. The HF-Ti-cultured cells also
      exhibited poor assembly of focal contacts, as visualized by vinculin
      immunofluorescence. Furthermore, in motility assays based on an in vitro wound
      model, cells cultured on HF-Ti migrated more slowly than cells cultured on other
      titanium surfaces. These data suggest that Saos-2 cells attach less effectively
      to the HF-Ti surface. The methods described in this study should be useful for
      assessing the initial interactions of cultured cells with various materials,
      including metals.

PMID- 16450123
TI  - Quantitative and spatial differences in the expression of tryptophan-metabolizing
      enzymes in mouse epididymis.
AB  - Previous reports have suggested that indoleamine 2,3-dioxygenase (IDO) activity
      is particularly important in mouse epididymis tissue. We show here, using reverse
      transcription/polymerase chain reaction assays, Northern assays, Western blotting
      experiments, and immunohistochemistry that IDO is indeed highly expressed in
      mouse epididymis, and that IDO mRNA distribution and protein location are
      precisely regionalized within the organ and within sub-territories of the
      proximal part of the epididymal duct, the so-called caput epididymidis. Within
      the caput epididymidis, both the principal and the apical cells have been shown
      to express IDO. On the contrary, tryptophan dioxygenase (TDO), a sister enzyme of
      IDO, is weakly and uniformly expressed in mouse epididymis and, in contrast to
      IDO, is also expressed in testis. In the epididymis, TDO protein expression has
      been found in a totally different cell type in the smooth muscle layer
      surrounding the epididymal tubules. Finally, IDO is not secreted into the
      epididymal lumen, whereas the testis-expressed TDO is present on the head of
      spermatozoa retrieved from the cauda epididymidis. On the basis of the various
      functions that have been associated with IDO/TDO, we discuss the putative impacts
      of IDO/TDO expression on the physiology of mammalian epididymis and spermatozoa.

PMID- 16450124
TI  - Glycosylation and sorting pathways of lysosomal enzymes in mussel digestive
      cells.
AB  - Our aim was to contribute to the understanding of the synthesis, maturation and
      activation of lysosomal enzymes in an invertebrate cellular model: the endo
      lysosomal system (ELS) of mussel digestive cells. The activities of 5'
      nucleotidase (AMPase), arylsulphatase (ASase) and acid phosphatase (AcPase),
      which are transported towards acidic compartments as membrane proteins, were
      localised by enzyme cytochemistry. AcPase activity was found within large
      heterolysosomes and residual bodies. ASase was located in endosomes,
      endolysosomes and heterolysosomes. AcPase and ASase activities were recorded
      within small vesicles and cisterns of the trans-Golgi network. Conversely, AMPase
      activity was primarily found in microvilli and apical vesicles and, less
      conspicuously, in lysosomes and the cis-side of the Golgi and the cis-Golgi
      network (CGN). In order to understand the processes of synthesis and maturation
      of these lysosomal enzymes, selected glycoconjugates were localised after lectin
      cytochemistry. N-acetylglucosamine, mannose and fucose residues were almost
      ubiquitous in the ELS, as were galactose residues, which were apparently less
      abundant. N-acetylglucosamine residues occurred in the inner membrane co
      localised with mannose residues within the lysosomal and pre-lysosomal acidic
      compartments. Based on these results, glycosylation and sorting pathways are
      proposed for both soluble and membrane enzymes. Unlike in mammalian cells, O
      glycosylation is fully completed in the CGN, mannose addition in N-glycosylation
      extends beyond the CGN and galactose addition is fully achieved at the
      intermediate side. Sorting of soluble lysosomal enzymes, as in crustaceans, is
      mediated by the indirect transport of membrane-linked proteins with GlcNAc1-P6Man
      residues that are removed in endolysosomes and heterolysosomes.

PMID- 16450125
TI  - Vagus nerve stimulation preferentially induces Fos expression in nitrergic
      neurons of rat esophagus.
AB  - To identify neurochemical phenotypes of esophageal myenteric neurons synaptically
      activated by vagal preganglionic efferents, we immunohistochemically detected the
      expression of Fos, an immediate early gene product, in whole-mount preparations
      of the entire esophagus of rats following electrical stimulation of the vagus
      nerves. When electrical stimulation was applied to either the cervical left (LVN)
      or right vagus nerve (RVN), neurons with nuclei showing Fos immunoreactivity (IR)
      were found to comprise approximately 10% of the total myenteric neurons in the
      entire esophagus. These neurons increased from the oral toward the gastric end of
      the esophagus, with the highest frequency in the abdominal portion of the
      esophagus. A significant difference was not found in the number of Fos neurons
      between the LVN-stimulated and RVN-stimulated esophagus. Double-immunolabeling
      showed that nitric oxide synthase (NOS)-IR occurred in most (86% and 84% in the
      LVN-stimulated and RVN-stimulated esophagus, respectively) of the Fos neurons in
      the entire esophagus. Furthermore, the stimulation of either of the vagus nerves
      resulted in high proportions (71%-90%) of Fos neurons with NOS-IR, with respect
      to the total Fos neurons in each segment, in the entire esophagus. However, a
      small proportion (8% and 7% in the LVN-stimulated and RVN-stimulated esophagus,
      respectively) of the Fos neurons in the esophagus exhibited choline
      acetyltransferase (ChAT)-IR. The occurrence-frequency of Fos neurons with ChAT-IR
      was less than 4% of the total Fos neurons in any segment of the LVN-stimulated
      and RVN-stimulated esophagus. Some of the Fos neurons with ChAT-IR appeared to be
      innervated by numerous varicose ChAT-positive nerve terminals. The present
      results showing that electrical stimulation of the vagus nerves induces a high
      proportion of Fos neurons with NOS-IR suggests the preferential activation of NOS
      neurons in the esophagus by vagal preganglionic efferents. This connectivity
      between the vagal efferents and intrinsic nitrergic neurons might be involved in
      inhibitory actions on esophageal motility.

PMID- 16450126
TI  - Combined therapy with desferrioxamine and deferiprone in beta thalassemia major
      patients with transfusional iron overload.
AB  - Iron overload is the main cause of morbidity and mortality especially from heart
      failure in patients with beta thalassemia major (TM). Successful iron chelation
      is therefore essential for the optimal management of TM. Although desferrioxamine
      (DFX) has been the major iron-chelating treatment of transfusional iron overload,
      compliance is a major hindrance in achieving optimal therapeutic results. The
      availability of oral iron chelation with deferiprone (L(1)) since 1987 is useful
      but showed poor efficacy when used alone as compared to DFX. We therefore decided
      to compare DFX alone with a prospective combined therapy with DFX and L(1) in
      beta thalassemia major patients with iron overload. We studied 91 patients with
      beta thalassemia major (mean age+/-SD, 15.02+/-5.8; range 2-30 years) attending
      the day care unit for regular transfusional support. They received packed red
      cells every 3-4 weeks to maintain pretransfusion hemoglobin concentration above 9
      g/dl. They had been receiving DFX at a daily dose of 40 mg kg(-1) day(-1) by
      subcutaneous infusion for 8-10 h on 4-5 nights each week for the past several
      years. However, due to various reasons, they had developed considerable
      transfusional iron overload. These patients were allocated to prospectively
      receive additional therapy with oral iron chelator L(1) at 75 mg kg(-1) day(-1)
      body weight in three divided doses with food after informed consent and continued
      to receive treatment with DFX as per the above dosage. Of the 91 patients, six
      developed severe gastrointestinal (GI) upset, two agranulocytosis, two
      arthropathy, one persistently raised liver enzymes, two died owing to sepsis, and
      two received allogeneic bone marrow transplantation. Amongst the remaining 76
      patients, 21 were found noncompliant (not taking DFX regularly, but taking L(1)
      regularly). Thus, in the 55 evaluable patients {6-48 months on combination
      therapy; mean [(+/-SD)22+/-12 months]}, the mean serum ferritin (+/-SD) fell
      dramatically from 3,088 (+/-1,299) ng/ml (DFX alone) to 2,051 (+/-935) ng/ml (DFX
      and L(1); p<0.001). It is interesting to note that there was also a significant
      improvement in the myocardial function as assessed by the ejection fraction
      (p<0.004) and fractional shortening (p<0.05) in those patients (n=42) who could
      be studied after being on combination therapy for a minimum of 1 year. The study
      emphasizes that beta thalassemia major patients with transfusional iron overload
      can be successfully treated with a combination of DFX and L(1). Our results also
      demonstrate a significant statistical improvement after as little as 6 months of
      combination therapy. Furthermore, these improvements lead to a progressive fall
      in the mean serum ferritin. Lastly, the study also demonstrates significant
      improvement in the echocardiographic parameters of myocardial performance in
      these patients receiving combination therapy.

PMID- 16450127
TI  - Thrombophilic mutations in Iranian patients with infertility and recurrent
      spontaneous abortion.
AB  - Factor V Leiden (FVL) G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T,
      and factor II (FII) G20210A mutations are three important causes of
      thrombophilia, the condition that might be related to infertility and recurrent
      spontaneous abortion (RSA). In this study we evaluated the presence of these
      three mutations in 36 female patients with unexplained infertility, 65 female
      patients with unexplained RSA, and 62 healthy fertile women as control group. DNA
      was extracted from peripheral blood samples and PCR-RFLP was performed for the
      molecular diagnosis of each mutation. In addition, activated protein C resistance
      (APC-R) was also evaluated. The frequencies of FVL, MTHFR, and FII mutations
      (heterozygous and homozygous) in the control group were 0.0%, 38.7%, and 3.2%,
      respectively. The frequency of FVL mutation in patients with infertility (30.6%)
      or RSA (20.0%) was significantly higher than that of the control group. A
      significantly higher MTHFR mutation rate was also observed in patients with RSA
      (63.1%) as compared to controls. However, the mutation rate of MTHFR in patients
      with infertility (50.0%) was not statistically different from that in controls.
      No significant difference was observed in the frequencies of FII mutations
      between the patients and controls. Decreased levels of APC-R were observed in
      25.0% of infertile patients and 18.9% of patients with RSA. In conclusion, our
      results show a skew towards higher mutation frequencies of FVL and MTHFR in
      patients that may necessitate detection of such mutations in these Iranian
      patients.

PMID- 16450128
TI  - Rational evaluation of urinary stone disease.
AB  - This article outlines the recent state of the art in the metabolic diagnosis of
      stone disease. The current literature in the field of urolithiasis-including the
      existing German and EAU-Guidelines as well as the Conference Book of the 1st
      International Consultation on Stone Disease-was critically reviewed. As far as
      possible the references were rated according to the EBM criteria. The occurrence
      of stone disease in the western world is increasing greatly. Modern lifestyle,
      dietary habits and excess weight-problems of affluent societies-are emerging as
      the important promoters of the "stone boom" in the new millennium. This even
      affects children, whose stone prevalence is otherwise significantly less than
      that of adults. Criteria for the high-risk group of stone formers were clearly
      defined. A diagnostic standard is formulated for the basic and the elaborate
      metabolic evaluation of a stone patient. The diagnostic pathways for the most
      important stone types and metabolic disorders, respectively, are described. The
      present concept allows a precise risk classification of each stone former and
      facilitates the decision whether stone-specific measures in addition to the basic
      metaphylaxis are recommendable or not.

PMID- 16450130
TI  - Dandy Walker variant and persistent occipital sinus at the museum La Specola in
      Florence.

PMID- 16450129
TI  - Characterization of LEAFY COTYLEDON1-LIKE gene in Helianthus annuus and its
      relationship with zygotic and somatic embryogenesis.
AB  - The Helianthus annuus LEAFY COTYLEDON1-LIKE (HaL1L) gene encodes a heme-activated
      protein 3 subunit of the CCAAT box-binding factor. The phylogenetic analysis
      indicates that HaL1L is closely related to LEAFY COTYLEDON1 (LEC1)-type of
      Arabidopsis thaliana. In particular, the peptide results homologous to the LEC1
      LIKE gene of A. thaliana, with which it shares a high amino acid sequence
      identity (56%). HaL1L transcripts are accumulated primarily at an early stage of
      sunflower embryogenesis. High levels of HaL1L messenger RNA (mRNA) have been
      detected in the developing embryo proper, suspensor, endosperm, integument, and
      integumentary tapetum cells, while in unfertilized ovules, HaL1L mRNA was present
      at rather low levels. In an attempt to examine the involvement of HaL1L on
      somatic embryogenesis, a somaclonal variant of H. annuus x H. tuberosus (EMB-2)
      that produces ectopic embryo- and shoot-like structures, arranged in clusters
      along leaf veins, was used. We found that the epiphyllous proliferation of
      ectopic embryos on EMB-2 leaves was associated to HaL1L mRNA accumulation. The
      detection of HaL1L transcripts was evident in somatic embryos at the heart- and
      early cotyledon-stage. On the contrary, no signal related to HaL1L transcript
      accumulation was observed in EMB-2 leaves characterized by the presence of shoot
      like structures. Together, these results support the conclusion that the
      transcription of the HaL1L gene is maintained both in zygotic and in somatic
      embryogenesis. In addition, the ectopic accumulation of HaL1L mRNA in parenchymal
      cells around the vascular bundles of epiphyllous leaves opens the possibility
      that HaL1L could also be involved in switching somatic cell fate towards
      embryogenic competence.

PMID- 16450131
TI  - Intraoperative MRI for interventional neurosurgical procedures and tumor
      resection control in children.
AB  - INTRODUCTION: Despite the introduction of neuronavigational systems, radical
      tumor removal is still problematic in many neurosurgical procedures. Thus, direct
      intraoperative imaging for tumor resection control was implemented with an
      intraoperative magnetic resonance imaging (ioMRI) scanner installed in the
      operating room. Whereas most procedures with ioMRI were carried out in adults, we
      summarize 7 years of experience using ioMRI in children for interventional
      neurosurgical procedures or for tumor resection control. METHOD: An open magnetic
      resonance scanner (Magnetom Open 0.2 T) was installed in the neurosurgical
      operating room. For tumor resection control, ioMRI was performed in 35
      procedures. After the ioMRI scans were analyzed with respect to quality, the
      identification of residual tumor was considered by the attending neuroradiologist
      and neurosurgeon. If residual tumor tissue was present, a new three-dimensional
      (3D) dataset was acquired to update the neuronavigation; subsequently, the tumor
      resection was extended. In all these procedures, the results of the ioMRI were
      checked by an early postoperative high-field magnetic resonance imaging (MRI)
      study. In addition, ioMRI was carried out in ten other children to monitor
      interventional neurosurgical procedures. RESULTS: In all children, ioMRI was
      adequate both for tumor resection control and monitoring of interventional
      procedures. Primary radical removal of tumor was reached in 40% as confirmed by
      ioMRI, but in 60% of the patients, the tumor resection procedure was extended
      after residual tumor was detected using the new 3D dataset for navigational
      update. By using ioMRI, radical tumor removal improved up to 83% as confirmed by
      early postoperative MRI. Procedure-related complications were not seen in our
      series. For all MR-guided biopsies, histology findings could be confirmed, and
      aspiration of intracranial cysts or abscesses could be monitored online.
      CONCLUSION: IoMRI using the open magnetom is suitable for detecting residual
      tumor tissue, can compensate for the phenomenon of brain shift using a new
      intraopertive 3D dataset for extended tumor resection, and is capable of
      monitoring interventional neurosurgical procedures. By using ioMRI for tumor
      resection control, the degree of tumor resection could be significantly improved.

PMID- 16450132
TI  - Skin-covered midline spinal anomalies: a report of four rare cases with a
      discussion on their genesis and milestones in surgical management.
AB  - BACKGROUND: The differential diagnosis for a dorsal midline mass presenting in a
      newborn encompasses a wide range of pathological conditions, including spinal
      dysraphisms, tumoral overgrowths including teratoma and hamartoma, disturbances
      in regression of fetal tail, and pseudotail formation. OBJECTIVES: To present (a)
      three rare cases of human tails and one case of tethered cord due to a midline
      anomaly resembling part of a human limb, (b) to discuss different kinds of
      clinical and pathological conditions which may be encountered in such newborns,
      (c) to hypothesize a theory about genesis of these congenital lesions, and (d) to
      remind drawbacks in preoperative evaluations and surgical management of these
      newborns. MATERIALS AND METHODS: Four newborns with dorsal midline malformations
      initially diagnosed as heterotopias are presented. Appropriate preoperative
      investigations and proper surgical interventions leading to resection of the
      lesions were performed. All four were skin-covered lesions containing well
      differentiated cellular elements of fat, vascular, muscular, bony, and
      cartilaginous origin. Midline spinal dysraphism was detectable both pre- and
      intraoperatively only in one case in which cord untethering was also performed
      along with the first surgical intervention. In the other three "tailed cases,"
      midline bone defect could not be detected in the available X-ray films;
      consequently, simple excision of the tail-like lesions was done. The first
      patient had to be explored for repeat untethering of the cord after 4 years, but
      the others have not yet developed any sign of tethering during an average period
      of 12 years follow-up. CONCLUSION: Morphological diagnosis of these lesions is
      not easy, and the attending pediatrician and neurosurgeon should be familiar with
      the differential diagnosis of such lesions and be prepared for possible time
      consuming operation mandatory to achieve total resection of the lesion in a
      newborn under general anesthesia. Reviewing the possible theories regarding the
      genesis of such anomalies, it is hypothesized and suggested that all similar
      cases could have been of hamartomatous origin rather than defects of
      embryogenesis.

PMID- 16450133
TI  - Cytochemical characterization of the third-stage larva of Wuchereria bancrofti
      (Nematoda: Filarioidea).
AB  - In the present paper, we report the results we obtained using several
      cytochemical techniques to analyze the infective larva of Wuchereria bancrofti.
      An imidazole osmium tetroxide solution was used to visualize unsaturated fatty
      acids. A highly contrasted material forming a continuous structure was observed
      on the larval surface and over the epicuticle. A strong reaction was observed on
      the esophagus and also on the inner secreted material. Carbohydrates containing
      vic-glycol groups were not observed on the cuticle of the third-stage larva of W.
      bancrofti submitted to the Thiery technique. Using a panel of eight gold-labeled
      lectins, we found that the cuticle exhibited slight labeling with all lectins
      used, indicating residues of N-acetyl-D: -glucosamine, N-acetyl-galactosamine, D:
      -galactose, D: -manose, and L: -fucose. Surface anionic sites were visualized by
      using cationized ferritin particles. Treatment with trypsin partially inhibited
      the reaction, whereas the treatment with chondroitinase ABC, a specific enzyme
      for glycosaminoglycans, completely abolished the labeling with cationic
      particles.

PMID- 16450135
TI  - Short fluorodeoxyuridine exposure of different human glioblastoma lines induces
      high-level accumulation of S-phase cells that avidly incorporate 125I
      iododeoxyuridine.
AB  - PURPOSE: Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy
      agent incorporated into DNA during the synthesis phase. In this study we sought
      to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA
      incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations.
      METHODS: Three human glioblastoma cell lines with different p53 expression were
      pre-treated with various FdUrd conditions. After different intervals, (125)I
      IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell
      cycle analysis was performed after identical intervals post FdUrd pre-treatment.
      RESULTS: The highest increase in (125)I-IdUrd DNA incorporation was induced by 1
      h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was
      greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline
      incorporation in the three cell lines. Furthermore, cell synchronisation in S
      phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24
      h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline. CONCLUSION:
      FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was
      maximal after an interval of 16-24 h and time-correlated with the highest radio
      IdUrd DNA incorporation. These observations might allow the rational design of an
      Auger radiation therapy targeting a maximal number of S-phase cells in single
      treatment cycles.

PMID- 16450136
TI  - 99mTc/188Re-labelled lipid nanocapsules as promising radiotracers for imaging and
      therapy: formulation and biodistribution.
AB  - PURPOSE: This study focuses on a promising carrier system for imaging and
      therapeutic purposes using lipid nanocapsules. To assess their potential for
      clinical use, we labelled nanocapsules with (99m)Tc and (188)Re and analysed some
      kinetic biodistribution parameters after intravenous injection in rats. METHODS:
      Lipophilic complexes [(99m)Tc/(188)Re(S(3)CPh)(2)(S(2)CPh)] ((99m)Tc/(188)Re-SSS)
      were encapsulated within the nanoparticles during their manufacture with
      quantitative yield and satisfactory radiochemical purity. Rats were injected
      intravenously with 3.7 MBq (99m)Tc/(188)Re-labelled nanocapsules and sacrificed
      at 5, 15 and 30 min and 1, 2, 4, 8, 12, 16, 20 and 24 h. RESULTS: Dynamic
      scintigraphic acquisitions showed predominant hepatic uptake, and ex vivo
      counting indicated a long circulation time of labelled nanocapsules, with a half
      life of 21+/-1 min for (99m)Tc and 22+/-2 min for (188)Re. Very weak urinary
      elimination was observed, indicating good stability of (99m)Tc and (188)Re
      labelling. CONCLUSION: (99m)Tc/(188)Re-SSS nanocapsules can be obtained with high
      yield and satisfactory radiochemical purity. The biodistributions of
      (99m)Tc/(188)Re-labelled nanocapsules are close to those of classical PEG-coated
      particles and show good stability of (188)Re/(99m)Tc-SSS labelling.

PMID- 16450137
TI  - Molecular imaging of cell transplantation in Parkinson's disease.

PMID- 16450139
TI  - The possible role of 68Ga-DOTATATE PET in malignant abdominal paraganglioma.

PMID- 16450138
TI  - Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb
      B inhibitor CI-1033.
AB  - PURPOSE: This study was designed as "proof of concept" for a drug development
      model utilising multi-tracer serial small animal PET imaging to characterise
      tumour responses to molecularly targeted therapy. METHODS: Mice bearing
      subcutaneous A431 human squamous carcinoma xenografts (n=6-8) were treated with
      the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6
      or 7) with [(18)F]fluorodeoxyglucose, [(18)F]fluoro-L: -thymidine, [(18)F]fluoro
      azoazomycinarabinoside or [(18)F]fluoromisonidazole. Separate cohorts (n=3) were
      treated identically and tumours were assessed ex vivo for markers of glucose
      metabolism, proliferation and hypoxia. RESULTS: During the study period, mean
      uptake of all PET tracers generally increased for control tumours compared to
      baseline. In contrast, tracer uptake into CI-1033-treated tumours decreased by 20
      60% during treatment. Expression of the glucose transporter Glut-1 and cell cycle
      markers was unchanged or increased in control tumours and generally decreased
      with CI-1033 treatment, compared to baseline. Thymidine kinase activity was
      reduced in all tumours compared to baseline at day 3 but was sevenfold higher in
      control versus CI-1033-treated tumours by day 6 of treatment. Uptake of the
      hypoxia marker pimonidazole was stable in control tumours but was severely
      reduced following 7 days of CI-1033 treatment. CONCLUSION: CI-1033 treatment
      significantly affects tumour metabolism, proliferation and hypoxia as determined
      by PET. The PET findings correlated well with ex vivo biomarkers for each of the
      cellular processes studied. These results confirm the utility of small animal PET
      for evaluation of the effectiveness of molecularly targeted therapies and
      simultaneously definition of specific cellular processes involved in the
      therapeutic response.

PMID- 16450140
TI  - Use of 11C-methionine PET to monitor the effects of temozolomide chemotherapy in
      malignant gliomas.
AB  - PURPOSE: The purpose of this study was to monitor the metabolic effects of
      temozolomide (TMZ) chemotherapy in malignant gliomas by means of repeated
      positron emission tomography (PET) with [(11)C]methionine (MET). METHODS: Fifteen
      patients with histologically proven malignant glioma were treated by TMZ
      chemotherapy. MET-PET studies were performed before and after the third cycle of
      TMZ chemotherapy in all patients, and in 12 patients also after the sixth cycle.
      Gadolinium-enhanced MRI studies were performed in 12 patients before the first
      and after the sixth cycle. Clinical status was assessed by the modified Rankin
      scale. Long-term outcome was assessed by calculating the time to progression
      (TTP) in months. RESULTS: Decline in MET uptake during therapy corresponded to a
      stable clinical status. The median TTP was significantly longer in patients with
      decline in MET uptake than in those with increasing MET uptake (23 vs 3.5 months;
      p=0.01, log rank test). There was no significant correlation between change in
      MET uptake and change in contrast enhancement during treatment for all patients.
      CONCLUSION: The present data demonstrate that clinical stability, which is often
      achieved under TMZ chemotherapy of malignant glioma, corresponds to a decline in
      or stability of tumour amino acid metabolism. Tumour responses can already be
      demonstrated with MET-PET after three cycles of chemotherapy, and absence of
      progression at that time indicates a high probability of further stability during
      the next three cycles. A reduction in MET uptake during TMZ treatment predicts a
      favourable clinical outcome. Molecular imaging of amino acid uptake by MET-PET
      offers a new method of measurement of the biological activity of recurrent
      glioma.

PMID- 16450142
TI  - An immune edited tumour versus a tumour edited immune system: Prospects for
      immune therapy of acute myeloid leukaemia.
AB  - Cell based therapies for acute myeloid leukaemia (AML) have made significant
      progress in the last decade benefiting the prognosis and survival of patients
      with this aggressive form of leukaemia. Due to advances in haematopoietic stem
      cell transplantation (HSCT) and particularly the advent of reduced intensity
      conditioning (RIC), the scope of transplantation has now extended to those
      patients previously ineligible due to age and health restrictions and has been
      associated with a decrease in transplant related mortality. The apparent graft
      versus leukaemia (GvL) effect observed following HSCT demonstrates the potential
      of the immune system to target and eradicate AML cells. Building on previously
      published pre-clinical studies by ourselves and others, we are now initiating a
      Phase I clinical study in which lentiviral vectors are used to genetically modify
      AML cells to express B7.1 (CD80) and IL-2. By combining allogeneic HSCT with
      immunisation, using the autologous AML cells expressing B7.1 and IL-2, we hope to
      stimulate immune eradication of residual AML cells in poor prognosis patients
      that have achieved donor chimerism. In this report we describe the background to
      cell therapy based approaches for AML, and discuss difficulties associated with
      the deployment of a chronically stimulated, hence exhausted/depleted immune
      system to eradicate tumour cells that have already escaped immune surveillance.

PMID- 16450141
TI  - First preclinical evaluation of mono-[123I]iodohypericin as a necrosis-avid
      tracer agent.
AB  - PURPOSE: We have labelled hypericin, a polyphenolic polycyclic quinone found in
      St. John's wort (Hypericum perforatum), with( 123)I and evaluated mono
      [(123)I]iodohypericin (MIH) as a potential necrosis-avid diagnostic tracer agent.
      METHODS: MIH was prepared by an electrophilic radioiodination method. The new
      tracer agent was evaluated in animal models of liver infarction in the rat and
      heart infarction in the rabbit using single-photon emission computed tomography
      (SPECT), triphenyltetrazolium chloride (TTC) histochemical staining, serial
      sectional autoradiography and microscopy, and radioactivity counting techniques.
      RESULTS: Using in vivo SPECT imaging, hepatic and cardiac infarctions were
      persistently visualised as well-defined hot spots over 48 h. Preferential uptake
      of the tracer agent in necrotic tissue was confirmed by perfect match of images
      from post-mortem TTC staining, autoradiography (ARX) and histology. Radioactivity
      concentration in infarcted tissues was over 10 times (liver; 3.51% ID/g in
      necrotic tissue vs 0.38% ID/g in normal tissue at 60 h p.i.) and over 6 times
      (myocardium; 0.36% ID/g in necrotic tissue vs 0.054% ID/g in normal tissue;
      ratios up to 18 for selected parts on ARX images) higher than in normal tissues.
      CONCLUSION: The results suggest that hypericin derivatives may serve as powerful
      necrosis-avid diagnostic agents for assessment of tissue viability.

PMID- 16450143
TI  - Interleukin 2 regulation following semi-allogeneic bone marrow transplantation in
      mice.
AB  - Success of allogeneic and autologous bone marrow transplantation (BMT) is
      hampered by susceptibility to infection during the first two post-treatment
      years. Further, in treating malignant diseases, impaired anti-host reactivity for
      donor cells may contribute to a high rate of relapse. Both complications are a
      consequence of immune deficiency involving B and T lymphocytes. The present study
      evaluates several key parameters of the immunologic reconstitution mechanism in
      mice subjected to myeloablative total body irradiation following semi-allogeneic
      (parental) BMT. This resulted in a gradual reduction of splenic CD3, CD4 and CD8
      cells until day 45 post-BMT. Concomitantly, there was an increase in monocytes
      and CD4+/CD8+ (double positive) cells, accompanied by a persistent elevation in
      the percentage of B lymphocytes. The total thymic and splenic T cell populations
      were reduced until day +30. The cellular reduction correlated with the poor
      proliferative response of the thymic and splenic cells. A decrease occurred in IL
      2 mRNA expression in thymic cells during days 15-20 post-transplant,
      corresponding with the low level of IL-2 secretion in the spleen and thymus of
      the transplanted mice. In conclusion, following semi-allogeneic BMT, there was an
      overall immune down-regulation in the cells, gene and protein levels. Reduced
      immunological responsiveness following BMT reinforces the need for improving the
      immune dysfunction by immunotherapy post-BMT.

PMID- 16450144
TI  - [Pre- and postnatal MRI of the fetus with complex intracranial vascular
      malformation].
AB  - Intracranial vascular malformations (IVM) on the whole occur in neonates very
      rarely. In such cases of IVM two different kinds can and must be discerned: (1)
      dural arteriovenous shunts (DAVS) and (2) vein of Galen aneurysmal malformations
      (VGAM). The latter seem to represent the majority of IVM of newborns. Several
      classifications are known for both types. Mortality of neonates and babies due to
      DAVS exceeds the average mortality from DAVS in adults. VGAM and DAVS can be
      diagnosed by prenatal ultrasonography only when the vessels behind the shunt are
      vasodilated because of the increasing flow stress. For that reason VGAM and DAVS
      are generally not recognized before the last trimenon or even postnatally. The
      prognosis of an IVM is influenced by the shunt capacity and its resulting cardiac
      stress as well as by the child's age. To plan the mostly interventional therapy,
      postnatal angiography (DSA) and MRI are employed and to an increasing extent also
      prenatal MRI examinations. We describe the case of a very complex IVM, the full
      dimensions of which could only be discerned by using pre- and postnatal MRI
      supplementary to the ultrasonography. Besides DAVS, flows from the pericallosal
      arteries as well as from the thalamic branches had to be considered. As a
      consequence DAVS and in addition VGAM existed in parallel.

PMID- 16450145
TI  - [Inflammatory lesions of the brainstem and the cerebellopontine angle].
AB  - Inflammatory lesions of the brainstem and the cerebellopontine angle are often
      critical for the patient, because crucial neuronal and vascular structures are
      found in this region. The patient's prognosis mainly depends on rapid
      identification of the inflammation site and the radiological evaluation of the
      inflammation pathogenesis to develop therapeutic strategies. Therefore, cross
      sectional imaging is complementary to laboratory and CSF analysis as well as
      biopsies. This article gives a survey of inflammatory lesions of the brainstem
      and the cerebellopontine angle.

PMID- 16450146
TI  - Idiopathic biliary perforation in a 10-year-old boy.
AB  - A 10-year-old boy of African origin with AIDS and Stage IV Hodgkin's lymphoma
      presented with a short history of abdominal distension and bile ascites shown to
      be due to a perforation of his common bile duct. This was treated initially by
      laparotomy, external peritoneal drainage and endoscopic biliary stenting although
      without success. He then underwent a laparotomy and biliary diversion (Roux-en-Y
      hepaticojejunostomy) with satisfactory resolution of his bile duct pathology.
      Although the co-morbid conditions are likely to be contributory factors, biliary
      perforation in either disease has not been reported before.

PMID- 16450147
TI  - [Increasingly appropriate depiction of rheumatology for G-DRG reimbursement
      2006].
AB  - Starting with the second year of the so called "convergence period", specialized
      rheumatological treatment is now represented by a specific DRG (197Z) in the
      German G-DRG system. The definition of this DRG is based on the procedure codes
      for the complex and multimodal treatment of rheumatological inpatients (OPS 8-983
      and 8-986). This will result in a more appropriate reimbursement of
      rheumatological treatment. The implementation of specialized rheumatological
      treatment can be regarded as exemplary for the incorporation of medical
      specializations into DRG systems. The first step is the definition of the
      characteristics by procedure codes, which can consequently be utilized within the
      grouping algorithm. After an inadequate representation of a medical
      specialization within the DRG system has been demonstrated, a new DRG will be
      established. As no cost data were available, the calculation of a cost weight for
      the new G-DRG 197Z is not yet possible for 2006. Hence, reimbursement has to be
      negotiated between the individual hospital and the budget commission of the
      health insurers. In this context, the use of clinical pathways is considered
      helpful.

PMID- 16450148
TI  - [Imaging methods in rheumatology: imaging in psoriasis arthritis (PsA)].
AB  - Conventional radiography is still the standard method of imaging in PsA since it
      displays many joints at the same time, thereby allowing different types of joint
      involvement to be recognized. Moreover, thanks to the high resolution of
      radiography, bony changes in a single joint are depicted in a brilliant way.
      Several features of psoriatic arthritis allow the distinction from rheumatoid
      arthritis, including the frequent involvement of the distal interphalangeal
      joints, asymmetry of joint involvement, axial involvement of finger joints,
      oligoarticular involvement; however, symmetric polyarthritis is also possible. At
      the level of the single joint, there are signs of severe destructive changes
      potentially leading to mutilation and at the same time signs of periostal bone
      proliferation and ankylosis may be present. Bony proliferation and/or osteolysis
      are not restricted to the joint region but can affect also the total phalanx with
      bone apposition or concentric osteolysis which may lead to a complete
      disappearance of phalanxes. For purposes of quantification of radiographic
      changes scoring methods are used that were originally developed for rheumatoid
      arthritis. So far, there is only one validated scoring method that was
      specifically designed for PsA and that takes into account both features of PsA,
      damage as well as proliferation of bone. In contrast to conventional radiography,
      MRI and sonography are able to visualize inflammatory processes within the soft
      tissue (joint capsules, tendon sheaths, tendon insertions, etc.), allowing an
      estimation of disease activity. Scintigraphy is nonspecific and can only be used
      to detect clinically silent inflammatory spots. The relatively frequent spinal
      (axial) involvement is similar to that seen in ankylosing spondylitis. However,
      unilateral sacroiliitis, asymmetry of syndesmophytes and development of
      parsyndesmophytes may distinguish PsA from ankylosing spondylitis. While
      conventional radiography demonstrates the bony consequences of inflammation in
      the spine, MRI also shows the active inflammatory changes in sacroiliacal joints
      and vertebrae.

PMID- 16450149
TI  - [5-HT3 receptor antagonist als analgetics in rheumatic diseases].
AB  - Various rheumatic diseases like fibromyalgia, systemic inflammatory rheumatic
      disorders and localized diseases, such as arthritides and activated arthroses,
      tendinopathies and periarthropathies, as well as trigger points can be improved
      considerably by treatment with the 5-HT3 receptor antagonist tropisetron.
      Particularly in the latter group of diseases, local injections have done
      surprisingly rapid analgesic action. This effect matches that of local
      anesthetics, but lasts considerably longer and is comparable to local injections
      of local anesthetics combined with corticosteroids. The action of the 5-HT3
      receptor antagonists can be attributed to an antinociceptive effect that occurs
      at the same time as an antiphlogistic and probably also an immunosuppressive
      effect. Whereas an inhibited release of substance P from the nociceptors, and
      possibly some other neurokins as well, seems to be the most likely explanation
      for the antinociceptive action, the antiphlogistic effect is primarily due to an
      inhibited formation of various different phlogistic substances; in some
      conditions, like systemic inflammatory rheumatic diseases, for example, the 5-HT3
      receptor antagonists may exert an immunosuppressive effect in addition to this.

PMID- 16450150
TI  - [T-large granular lymphocyte leukaemia. An important differential diagnosis to
      Felty's syndrome].
AB  - T-Large Granular Lymphocyte (T-LGL) leukaemia is a rare clonal disease
      characterized by neutropenia and/or anaemia. Because of its strong association
      with rheumatoid arthritis (RA), T-LGL leukaemia is an important differential
      diagnosis to Felty's syndrome. This differentiation might be especially difficult
      since, in severe RA with extraarticular manifestations, there is often an
      expanded memory effector T-cell population which can hardly be separated from T
      LGL leukaemia cells by means of immunophenotyping. The main criterion for T-LGL
      leukaemia is the detection of a clonal T-cell-receptor rearrangement by PCR.
      First-line therapy consists of weekly low-dose methotrexate. Alternatively, other
      immunosuppressives or cytotoxic agents can be useful. There are very limited data
      from therapy studies. The German CLL study group has initiated a protocol using
      parenteral low-dose methotrexate as first-line therapy and fludarabine as second
      line medication.

PMID- 16450151
TI  - [4th Joint Workshop of the Competence Network Rheumatism and the Rheumatism
      Centers' Cooperative. 7-10 April 2005, Heidelberg].

PMID- 16450152
TI  - [Radiosynoviorthesis].
AB  - Intraarticular therapy is an established form of therapy in chronic inflammatory
      joint diseases. Besides the injection of glucocorticoids, radiosynoviorthesis is
      a frequently used procedure. Intraarticular injected beta-emitting radionuclides
      are indicated in chronic synovitis with recurrent joint effusions in rheumatoid
      arthritis, seronegative spondyloarthritis, villonodular synovitis after surgery
      and for bleeding prophylaxis in haemophilic arthropathy. The value of
      radiosynoviorthesis in activated osteoarthritis is not yet clarified.

PMID- 16450153
TI  - [Polyarteritis nodosa - a "classical" case].
AB  - Diagnosis of polyarteritis nodosa is often delayed due to the vast heterogeneity
      of initial clinical symptoms. The case presented shows the clinical image of the
      disease, leading from the first symptoms up to verification of the diagnosis by
      sural-nerve biopsy. We discuss the classification of the disease among other
      types of vasculitis, the classification criteria proposed by the American College
      of Rheumatology (ACR) as well as current therapeutic options. This case
      underlines the interdisciplinary character of the disease, challenging
      neurologists, dermatologists, rheumatologists and orthopedics alike.

PMID- 16450154
TI  - Expression analysis of barley (Hordeum vulgare L.) during salinity stress.
AB  - Barley (Hordeum vulgare L.) is a salt-tolerant crop species with considerable
      economic importance in salinity-affected arid and semiarid regions of the world.
      In this work, barley cultivar Morex was used for transcriptional profiling during
      salinity stress using a microarray containing approximately 22,750 probe sets.
      The experiment was designed to target the early responses of genes to a salinity
      stress at seedling stage. We found a comparable number of probe sets up-regulated
      and down-regulated in response to salinity. The differentially expressed genes
      were broadly characterized using gene ontology and through expression-based
      hierarchical clustering to identify interesting features in the data. A prominent
      feature of the response to salinity was the induction of genes involved in
      jasmonic acid biosynthesis and genes known to respond to jasmonic acid treatment.
      A large number of abiotic stress (heat, drought, and low temperature) related
      genes were also found to be responsive to salinity stress. Our results also
      indicate osmoprotection to be an early response of barley under salinity stress.
      Additionally, we compared the results of our studies with two other reports
      characterizing gene expression of barley under salinity stress and found very few
      genes in common.

PMID- 16450155
TI  - Hydrochlorothiazide efficacy and polymorphisms in ACE, ADD1 and GNB3 in healthy,
      male volunteers.
AB  - OBJECTIVE: The antihypertensive effect of thiazide diuretics has recently been
      associated with genetic variation in the angiotensin I-converting enzyme (ACE),
      alpha-adducin (ADD1) and the G protein subunit beta3 (GNB3). Analysis of short
      term diuretic effects may provide insight into the mechanisms behind these
      findings. METHODS: A total of 103 male volunteers took 25 and 100 mg
      hydrochlorothiazide (HCT) after a placebo day, each. We measured volume, sodium,
      chloride, potassium, calcium excretion, blood pressure and heart rate. RESULTS:
      Excretion and cardiovascular parameters were highly constant between the 2
      placebo days. The resting heart rate was 2-3 beats/minute (bpm) higher per ACE
      insertion allele on all 4 study days. The HCT-induced excretion of sodium,
      chloride and volume was independent of the genotypes. The additional potassium
      excretion induced by 100 mg HCT was 44+/-21, 33+/-27 and 16+/-26 mmol (mean+/-SD,
      p<0.001) in ACE II, ID and DD carriers and the same trend was observed after 25
      mg HCT. As a second finding, the 100 mg HCT-induced calcium retention was 0.2+/
      1.2, 0.7+/-0.8 and 1.7+/-2.1 mmol in ADD1 Gly/Gly, Gly/Trp and Trp/Trp carriers
      (p=0.002) and the same trend existed after 25 mg HCT. CONCLUSION: The effects of
      genetic polymorphisms were stronger with the higher diuretic dose. ACE insertion
      allele carriers appeared to be more prone to hypokalaemia than deletion allele
      carriers. ADD1 Trp460 carriers may especially benefit from the calcium-sparing
      effect of thiazides. Both associations should be further studied in long-term
      treatment with thiazide diuretics.

PMID- 16450156
TI  - Posturography frequency analysis of sound-evoked body sway in normal subjects.
AB  - Sound-evoked activation of the vestibular system has been suggested for a long
      time, and myogenic potentials have been recorded at the level of different
      muscular groups while a high intensity sound was applied. The aim of this study
      was to analyse sound-evoked postural responses in normal subjects and to
      correlate them with the activation of the vestibular system. Body sway was
      measured by posturography and elaborated through spectral frequency analysis in
      40 healthy volunteers in the basal condition and after applying a sound stimulus
      monoaurally. Spectral frequency analysis results showed a significant increase,
      in presence of stimulus, of body sway at low and middle frequencies only on the
      lateral plane and in the closed-eyes condition. As it seems that these frequency
      ranges are mainly under vestibular control, our results suggest that sound
      activates specifically the vestibular system, and posturography during sound
      stimulation represents an alternative approach to assess vestibular function.

PMID- 16450157
TI  - Upper airway surgery: the effect on nasal continuous positive airway pressure
      titration on obstructive sleep apnea patients.
AB  - The objective of this study was to observe the change in CPAP pressure after
      nasal and/or tonsil surgery in a retrospective study involving 17 patients unable
      to tolerate CPAP titration. All patients had two polysomnography studies for
      titration: one before and another subsequent to upper airway surgical treatment.
      The results showed a mean age of 49 +/- 9 years, a body mass index of 30 +/- 4
      kg/m(2) and an apnea-hypopnea index of 38 +/- 19. Surgical procedures were
      radiofrequency reduction of the inferior turbinate (eight patients), septoplasty
      (one patient), septoplasty with inferior turbinectomy (two patients), septoplasty
      with inferior turbinate submucosal diathermy (two patients), septoplasty with
      tonsillectomy (two patients), septoplasty with inferior turbinate submucosal
      diathermy and tonsillectomy (one patient) and tonsillectomy (one patient). CPAP
      titration before and after surgery had respectively a mean pressure of 12.4 +/-
      2.5 and 10.2 +/- 2.2 cmH(2)O ( P = 0.001). Maximum CPAP pressure was 16.4 cmH(2)O
      before and 13 cmH(2)O after surgery. A pressure reduction > or =1 cmH(2)O
      occurred in 76.5% of the patients and > or =3 cmH(2)O in 41.1%. Upper airway
      surgical treatment appears to have some benefit by reducing nasal CPAP pressure
      levels. The effect seems to be greater when the prior pressure was > or =14
      cmH(2)O.

PMID- 16450158
TI  - Agreement of medical decisions in occupational health as a quality requirement.
AB  - OBJECTIVE: Workers' medical examination by the occupational physician (OPs) is a
      decision-making process whose output consists of a variety of evaluations,
      including assessment of fitness for work. The medical literature reports that
      there is no complete agreement among OPs assessing the same workers, evidencing a
      critical aspect of professional performance. This study aims at evaluating the
      inter-individual variability of medical decisions by different occupational
      physicians. METHODS: Four specialists in occupational medicine participated in
      the study. Each specialist examined 100 records of subjects with different
      medical conditions selected from about 2,500 health care workers. Each physician
      completed a form including the following items: assessment of fitness for work,
      advice to workers, need of further investigations, report of occupational
      disease, recommendation for the general practitioner. To assess the inter
      individual variability the percent agreement and the agreement strength or
      Cohen's kappa were measured. RESULTS: The study shows a variable agreement in the
      assessment of fitness for work among different professionals, with percent
      agreement ranging from 58% for the whole group to an average of 77% for
      physicians' pairs. By taking into account the variability expected by chance, the
      agreement ranged from fair to substantial. The agreement of other decisions
      (workers' advice, referral to other specialists, request of further
      investigation, report of occupational disease, recommendation for the general
      practitioner) was more variable. CONCLUSION: The study shows that an inter
      individual variability exists for some decisions taken by OPs. According to the
      need to continuously improve professional practice, in the absence of qualitative
      standards based on the outcome, reduction of inter-individual variability that
      should be considered as a quality requirement of the performance of the
      occupational physician.

PMID- 16450160
TI  - Varicella-related complications and hospitalisations in a tertiary pediatric
      medical center before vaccine introduction.

PMID- 16450159
TI  - Primitive neuroectodermal tumor of the brain in a girl with Turner syndrome
      diagnosed after 4 years of growth hormone therapy.

PMID- 16450162
TI  - MRI diagnosis of spontaneous uterine rupture of an unscarred uterus.
AB  - Spontaneous uterine rupture is a rare, potentially catastrophic complication of
      pregnancy, and its prompt diagnosis and treatment are essential in limiting
      morbidity and mortality. Clinical diagnosis is difficult and relies heavily on
      diagnostic imaging. Radiological diagnosis is also often difficult with most
      documented cases involving the use of ultrasound and computed tomography.
      Although magnetic resonance imaging (MRI) is being used more frequently to assess
      patients, there are few reports illustrating the utility of MRI and its
      advantages over other imaging modalities in the diagnosis of uterine rupture.
      This report documents a case of spontaneous uterine rupture diagnosed by MRI in a
      postpartum patient with an unscarred uterus.

PMID- 16450161
TI  - Optimizing the use of aromatase inhibitors in adjuvant therapy for postmenopausal
      patients with hormone-responsive early breast cancer: current and future
      prospects.
AB  - PURPOSE: Five years of tamoxifen treatment after primary surgery has had a
      significant impact on outcomes for women with early breast cancer, but the third
      generation aromatase inhibitors (AIs) are now challenging tamoxifen as the gold
      standard endocrine adjuvant treatment. Results from two large, phase III, early
      adjuvant studies have indicated that the AIs letrozole and anastrozole offer
      greater protection against recurrence than tamoxifen in upfront substitution
      strategies in the first 5 years after surgery. Similarly, changeover to an AI
      (exemestane or anastrozole) after 2-3 years of tamoxifen has been shown to offer
      greater protection against recurrence than 5 years of tamoxifen. More than 50% of
      early breast cancer recurrences occur five or more years after surgery. Letrozole
      has been shown to offer greater protection against recurrence than placebo in the
      5 years after a standard course of tamoxifen. The safety implications of
      treatment with these potent AIs for 5 years or more are being closely monitored.
      Anticipated effects of estrogen deprivation on bone health may be treatable with
      bisphosphonates, and this strategy is under investigation. Effects on the
      cardiovascular system, and other estrogen-sensitive systems such as the central
      nervous system, are currently unclear and further results are awaited.
      CONCLUSION: Current evidence indicates that the third-generation AIs will improve
      outcomes for many women with early breast cancer.

PMID- 16450163
TI  - Lack of efficacy of imatinib in a patient with metastatic Leydig cell tumor.
AB  - Imatinib is a tyrosine kinase inhibitor with activity in gastrointestinal stromal
      tumor and a variety of other solid and hematological malignancies. Studies in
      vitro and in a mouse model suggested that the imatinib might also be active in
      malignant Leydig cell tumor. We report on the--to our knowledge--first treatment
      experiment with imatinib in a patient with metastatic Leydig cell tumor.
      Unfortunately, the tumor progressed during treatment.

PMID- 16450165
TI  - Interactions between cadence and power output effects on mechanical efficiency
      during sub maximal cycling exercises.
AB  - The purpose of this study was to investigate the interactions between cadence and
      power output effects on cycling efficiency. Fourteen healthy subjects performed
      four constant power output-tests (40, 80, 120 and 160 W) in which the cadence
      varied in five bouts from 40 to 120 rpm. Gross efficiency (GE) was determined
      over the last ten respiratory cycles of each bout and was calculated as the ratio
      of mechanical energy to energy expenditure. Results showed that (1) GE-cadence
      relationships reached a maximum at each power output corresponding to the cadence
      maximising efficiency (CAeff) and (2) GE increased with power output whatever the
      cadence until a maximal theoretical value. Moreover, interactions were found
      between these two factors: the cadence effect decreased linearly with power
      output and the power output effect increased exponentially with cadence.
      Consequently, cycling efficiency decreased more when cadence differed from CAeff
      at low than at high power output, and increased more with power output at high
      cadence than at low cadence. These interactions between cadence and power output
      effects on GE were mainly due to cadence and power output effects on the energy
      expenditure shares not contributing to power production.

PMID- 16450166
TI  - Maximal voluntary hyperpnoea increases blood lactate concentration during
      exercise.
AB  - Ventilatory work during heavy endurance exercise has not been thought to
      influence systemic lactate concentration. We evaluated the effect of maximal
      isocapnic volitional hyperpnoea upon arterialised venous blood lactate
      concentration ([lac-]B) during leg cycling exercise at maximum lactate steady
      state (MLSS). Seven healthy males performed a lactate minimum test to estimate
      MLSS, which was then resolved using separate 30 min constant power tests
      (MLSS=207+/-8 W, mean +/- SEM). Thereafter, a 30 min control trial at MLSS was
      performed. In a further experimental trial, the control trial was mimicked except
      that from 20 to 28 min maximal isocapnic volitional hyperpnoea was superimposed
      on exercise. Over 20-28 min minute ventilation, oxygen uptake, and heart rate
      during the control and experimental trials were 87.3+/-2.4 and 168.3+/-7.0 l min(
      1) (P<0.01), the latter being comparable to that achieved in the maximal phase of
      the lactate minimum test (171.9+/-6.8 l min(-1)), 3.46+/-0.20 and 3.83 +/- 0.20 l
      min(-1) (P<0.01), and 158.5+/-2.7 and 166.8+/-2.7 beats min(-1) (P<0.05),
      respectively. From 20 to 30 min of the experimental trial [lac-]B increased from
      3.7+/-0.2 to 4.7+/-0.3 mmol l(-1) (P<0.05). The partial pressure of carbon
      dioxide in arterialised venous blood increased approximately 3 mmHg during
      volitional hyperpnoea, which may have attenuated the [lac-]B increase. These
      results show that, during heavy exercise, respiratory muscle work may affect [lac
      ]B. We speculate that the changes observed were related to the altered lactate
      turnover in respiratory muscles, locomotor muscles, or both.

PMID- 16450167
TI  - Influence of menstrual cycle phase on pulmonary function in asthmatic athletes.
AB  - The main aim of this study was to investigate whether there is a relationship
      between menstrual cycle phase and exercise-induced bronchoconstriction (EIB) in
      female athletes with mild atopic asthma. Seven eumenorrheic subjects with regular
      28-day menstrual cycles were exercised to volitional exhaustion on day 5 [mid
      follicular (FOL)] and day 21 [mid-luteal (LUT)] of their menstrual cycle.
      Pulmonary function tests were conducted pre- and post-exercise. The maximal
      percentage decline in post-exercise forced expiratory volume in 1 s (FEV(1)) and
      forced expiratory flow from 25 to 75% of forced vital capacity (FEF(25-75%)) was
      significantly greater (P<0.05) on day 21 (mid-LUT phase) (-17.35+/-2.32 and 
      26.28+/-6.04%, respectively), when salivary progesterone concentration was
      highest, compared to day 5 (mid-FOL phase) (-12.81+/-3.35 and -17.23+/-8.20%,
      respectively), when salivary progesterone concentration was lowest. The
      deterioration in the severity of EIB during the mid-LUT phase was accompanied by
      worsening asthma symptoms and increased bronchodilator use. There was a negative
      correlation between the percent change in pre- to post-exercise FEV(1) and
      salivary progesterone concentration. However, no such correlation was found
      between salivary estradiol and the percentage change in pre- to post-exercise
      FEV(1). This study has shown for the first time that menstrual cycle phase is an
      important determinant of the severity of EIB in female athletes with mild atopic
      asthma. Female asthmatic athletes may need to adjust their training and
      competition schedules to their menstrual cycle and to consider the potential
      negative effects of the LUT phase of the menstrual cycle on exercise performance.

PMID- 16450168
TI  - Facial cold-induced vasodilation and skin temperature during exposure to cold
      wind.
AB  - One purpose of this study was to characterize the facial skin temperature and
      cold-induced vasodilation (CIVD) response of 12 subjects (six males and six
      females) during exposure to cold wind (i.e., -10 to 10 degrees C; 2, 5, and 8 m/s
      wind speed). This study found that at each wind speed, facial skin temperature
      decreased as ambient temperature decreased. The percentage of subjects showing
      facial CIVD decreased significantly at an ambient temperature above -10 degrees
      C. A similar CIVD percentage was observed between 0 degrees C dry and 10 degrees
      C wet (face sprayed with fine water mist) at each wind speed. No CIVDs were
      observed during the 10 degrees C dry condition at any wind speed. The incidence
      of CIVD response was more uniform across facial sites when there was a greater
      cold stress (i.e., -10 degrees C and 8 m/s wind). Another objective of the study
      was to examine the effect of the thermal state of the body (as reflected by core
      temperature) on the facial skin temperature response during rest and exercise.
      This study found that nose skin temperature was significantly higher in
      exercising subjects with an elevated core temperature even though there was no
      significant difference in face skin temperature between the two conditions.
      Therefore, this finding suggests that acral regions of the face, such as the
      nose, are more sensitive to changes in the thermal state of the body, and hence
      will stay warmer relative to other parts of the face during exercise in the cold.

PMID- 16450169
TI  - Characterization and functional analysis of a pollen-specific gene st901 in
      Solanum tuberosum.
AB  - A pollen-specific gene, sb401, which was isolated from a cDNA library of in vitro
      geminated pollen of the diploid potato species Solanum berthaultii, belongs to
      the class of genes expressed late during pollen development. Using sb401 as a
      probe, a pollen-specific gene st901 was isolated from the genomic library of a
      potato species Solanum tuberosum cv. Desiree. Sequencing and RT-PCR analysis
      showed that the st901 genomic gene is 2,889 bp long, contains three exons and two
      introns, and encodes a putative polypeptide of 217 residues. The predicted
      protein sequence contains four imperfect repeated motifs of V-V-E-K-K-N/E-E; the
      core sequence of the repeats (K-K-N/E-E) resembles a microtubule-binding domain
      of the microtubule-associated protein MAP1B from mouse. The examination of a
      promoter-reporter construct in transgenic potato plants revealed that the st901
      is expressed exclusively in mature pollen grains, which is consistent with the
      results of Northern blot and RT-PCR. For analysis of the function of st901,
      transgenic plants harboring antisense copies of st901 cDNA driven by a native
      st901 promoter were generated. Suppression of st901 gene in potato resulted in
      aberrant pollen at maturation and pollen viability of transgenic plants ranged
      from 4.4 to 14.8%, while that of control plants were more than 90%. These results
      strongly suggest that st901 has an essential role in pollen development.

PMID- 16450170
TI  - Higher extracellular pH suppresses tracheary element differentiation by affecting
      auxin uptake.
AB  - In an optimized liquid medium containing auxin and cytokinin, mesophyll cells
      isolated from Zinnia elegans L. seedlings can be induced to differentiate into
      tracheary elements (TEs) at high frequency. However, it is known that buffering
      the medium at neutral pH severely suppresses TE differentiation. In the process
      of modifying the medium, we found that excessive administration of auxin restored
      the suppression. Based on this finding, we physiologically characterized auxin
      actions involved in TE differentiation by focusing on the influence of
      extracellular pH. First, dose/response relationships between auxin [1
      naphthaleneacetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D)]
      concentrations and differentiated cell ratios were determined under various
      extracellular pH conditions. Secondly, intracellular concentrations of free forms
      and metabolites of auxin species were determined by analyzing extracts from cells
      cultured with radiolabeled NAA and 2,4-D under different extracellular pH
      conditions with liquid scintillation counting and thin-layer chromatography
      autoradiograms. Higher extracellular pH was found to reduce both the auxin
      potency for inducing TE differentiation and intracellular auxin accumulation.
      Reduction levels correlatively varied depending on the auxin species. These
      results suggest that the weakening in auxin potency at higher extracellular pH is
      ascribed to lower auxin uptake, which leads to decreased intracellular perception
      of the auxin signal. A model to predict auxin action that considers membrane
      transport, metabolism, and the perception of auxin is also presented.

PMID- 16450171
TI  - Cytotoxic thio-malate is transported by both an aluminum-responsive malate efflux
      pathway in wheat and the MAE1 malate permease in Schizosaccharomyces pombe.
AB  - Aluminum (Al) tolerance in wheat (Triticum aestivum L.) is mainly achieved by
      malate efflux, which is regulated by the expression of the recently identified
      gene, presumably encoding an Al-activated malate efflux transporter (ALMT1).
      However, the transport mechanism is not fully understood, partly as a result of
      the rapid turnover of its substrate. We developed a tool to study malate
      transport in wheat by screening biological compounds using the well-characterized
      Schizosaccharomyces pombe malate transporter (SpMAE1). Expression of SpMAE1 in
      both S. pombe and Saccharomyces cerevisiae, which has no SpMAE1 homologue, caused
      hypersensitivity to thio-malic acid. This hypersensitivity was prominent at pH
      3.5, but not pH 4.5, and was accompanied by an increase in thiol content,
      indicating that SpMAE1 mediates the uptake of thio-malic acid at a specific low
      pH. In wheat, root apices were able to accumulate thio-malic acid without growth
      reduction at pH values above 4.2. Pretreatment of root apices with thio-malic
      acid followed by Al treatment induced thio-malate efflux. Al-induced thio-malate
      efflux was much higher in Al-resistant cultivars/genotypes than in Al-sensitive
      ones, and was accompanied by a decrease in thiol-content. Thio-malate efflux in
      the Al-resistant cultivar was slightly activated by lanthanum or ytterbium ion.
      Thio-malic acid did not alleviate the Al-induced inhibition of root elongation in
      wheat. Taken together, our results suggest that thio-malate acts as an analogue
      for malate in malate transport systems in wheat and yeast, and that it may be a
      useful tool for the analysis of malate transport involved in Al-tolerance and of
      other organic ion transport processes.

PMID- 16450173
TI  - Structure and enzyme expression in photosynthetic organs of the atypical C4 grass
      Arundinella hirta.
AB  - In its leaf blade, Arundinella hirta has unusual Kranz cells that lie distant
      from the veins (distinctive cells; DCs), in addition to the usual Kranz units
      composed of concentric layers of mesophyll cells (MCs) and bundle sheath cells
      (BSCs; usual Kranz cells) surrounding the veins. We examined whether
      chlorophyllous organs other than leaf blades--namely, the leaf sheath, stem,
      scale leaf, and constituents of the spike--also have this unique anatomy and the
      C4 pattern of expression of photosynthetic enzymes. All the organs developed DCs
      to varying degrees, as well as BSCs. The stem, rachilla, and pedicel had C4-type
      anatomy with frequent occurrence of DCs, as in the leaf blade. The leaf sheath,
      glume, and scale leaf had a modified C4 anatomy with MCs more than two cells
      distant from the Kranz cells; DCs were relatively rare. An immunocytochemical
      study of C3 and C4 enzymes revealed that all the organs exhibited essentially the
      same C4 pattern of expression as in the leaf blade. In the scale leaf, however,
      intense expression of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
      occurred in the MCs as well as in the BSCs and DCs. In the leaf sheath, the
      distant MCs also expressed Rubisco. In Arundinella hirta, it seems that the ratio
      of MC to Kranz cell volumes, and the distance from the Kranz cells, but not from
      the veins, affects the cellular expression of photosynthetic enzymes. We suggest
      that the main role of DCs is to keep a constant quantitative balance between the
      MCs and Kranz cells, which is a prerequisite for effective C4 pathway operation.

PMID- 16450174
TI  - Ultrastructure of cell contacts of fetal and adult Leydig cells in the rat: a
      systematic study from birth to senium.
AB  - Differentiation, development, and function of Leydig cells in the testis are
      regulated also by macrophages, vascular endothelial cells, and peritubular cells
      in the testis. The aim of the present study was to investigate the possible
      morphological substrates for communication between these cells. The cell contacts
      between adjacent Leydig cells, and between Leydig cells and other interstitial
      cells were studied electron microscopically in the rat testis of various age
      groups from birth to senium. Intercellular bridges with continuous cytoplasm were
      observed between fetal Leydig cells (FLCs) in the early postnatal period. Gap
      junctions were present in nearly every age group. A structural diversity as well
      as an increased occurrence of gap junctions with the maturity of the Leydig cells
      was noted. Coated pits were observed initially on pnd 30. From pnd 50 onwards,
      macrophages and Leydig cells were attached very closely to each other, when the
      cell processes of Leydig cells protruded either into the coated pits or into the
      deep invaginations of macrophages. To conclude, this is the first report on the
      presence of intercellular bridges between FLCs suggesting a possible functional
      synchronization of interconnected Leydig cells. The cell contacts observed here
      are possibly required for a precise communication between the Leydig cells and
      other interstitial cells.

PMID- 16450172
TI  - Isolation of a cDNA clone (PcSrp) encoding serine-rich-protein from Porteresia
      coarctata T. and its expression in yeast and finger millet (Eleusine coracana L.)
      affording salt tolerance.
AB  - A 1.4 Kb cDNA clone encoding a serine-rich protein has been isolated from the
      cDNA library of salt stressed roots of Porteresia coarctata, and designated as P.
      coarctata serine-rich-protein (PcSrp) encoding gene. Northern analysis and in
      situ mRNA hybridization revealed the expression of PcSrp in the salt stressed
      roots and rhizome of P. coarctata. However, no such expression was seen in the
      salt stressed leaves and in the unstressed tissues of root, rhizome and leaf,
      indicating that PcSrp is under the control of a salt-inducible tissue-specific
      promoter. In yeast, the PcSrp conferred increased NaCl tolerance, implicating its
      role in salinity tolerance at cellular level. Further, PcSrp was cloned
      downstream to rice Actin-1 promoter and introduced into finger millet through
      particle-inflow-gun method. Transgenic plants expressing PcSrp were able to grow
      to maturity and set seed under 250 mM NaCl stress. The untransformed control
      plants by contrast failed to survive under similar salt stress. The stressed
      roots of transgenic plants invariably accumulated higher Na(+) and K(+) ion
      contents compared to roots of untransformed plants; whereas, shoots of
      transgenics accumulated lower levels of both the ions than that of untransformed
      plants under identical stress, clearly suggesting the involvement of PcSrp in ion
      homeostasis contributing to salt tolerance.

PMID- 16450175
TI  - Substrate specificity of inner membrane peptidase in yeast mitochondria.
AB  - The inner membrane protease (IMP) cleaves intra-organelle sorting peptides from
      precursor proteins in mitochondria of the yeast Saccharomyces cerevisiae. An
      unusual feature of the IMP is the presence of two catalytic subunits, Imp1p and
      Imp2p, which recognize distinct substrate sets even though both enzymes belong to
      the same protease family. This nonoverlapping substrate specificity was
      hypothesized to result from the recognition of distinct residues at the P'1
      position (also termed +1 position) in the protease substrates. Here, we
      constructed an extensive series of mutations to obtain a profile of the critical
      cleavage site residues in IMP substrates and conclude that Imp1p, and not Imp2p,
      recognizes specific P'1 residues. In addition to its specificity for P'1
      residues, Imp1p also shows substrate specificity for the P3 (-3) position. In
      contrast, Imp2p recognizes the P1 (-1) position and the P3 position. Based on
      this new understanding of IMP substrate specificity, we conducted a survey for
      candidate IMP substrates in mammalian mitochondria and found consensus Imp2p
      cleavage sites in mammalian precursors to cytochrome c1 and glycerol-3-phosphate
      (G-3-P) dehydrogenase. Presence of a putative Imp2p cleavage site in G-3-P
      dehydrogenase was surprising, as its yeast ortholog contains an Imp1p cleavage
      site. To address this issue experimentally, we performed the first co-expression
      of mammalian IMP with proposed mammalian IMP precursors in yeast and show that
      murine precursors to cytochrome c1 and G-3-P dehydrogenase are cleaved by murine
      Imp2p. These results suggest, surprisingly, G-3-P dehydrogenase has switched from
      Imp1p in yeast to Imp2p in mammals.

PMID- 16450176
TI  - Heart rate regularity analysis obtained from pulse oximetric recordings in the
      diagnosis of obstructive sleep apnea.
AB  - Approximate entropy (ApEn) is a technique that can be used to quantify the
      irregularity or variability of time series. We prospectively evaluated the
      validity of ApEn of heart rate data obtained from pulse oximetric recordings as a
      diagnostic test for obstructive sleep apnea (OSA) in patients clinically
      suspected of suffering this disease. A sample of 187 referred outpatients (147
      men and 40 women), with a mean age of 57.9+/-12.8 years and a body mass index of
      29.5+/-5.5 kg/m(2), clinically suspected of having OSA were studied using
      nocturnal pulse oximetric recording performed simultaneously with complete
      polysomnography. A diagnosis of OSA was confirmed in 111 (59.3%). Patients with
      OSA presented significantly higher ApEn levels than those without OSA (1.334+/
      0.189 vs 1.167+/-0.182). Chronic obstructive pulmonary disease (COPD) was
      diagnosed for 42 patients. Among these patients, 22 (52.4%) were diagnosed with
      OSA. COPD patients with OSA showed significantly higher ApEn levels than COPD
      patients without OSA (1.337+/-0.193 vs 1.184+/-0.173; p=0.01). ApEn correlated
      significantly with apnea-hypopnea index (r=0.38; p=0.000). There was no
      significant correlation between ApEn and either age or body mass index. No
      significant changes were observed in ApEn throughout the night in OSA patients.
      Using receiver operating characteristic curve analysis, we obtained a diagnostic
      sensitivity of 71.2%, specificity of 78.9%, positive predictive value of 81.3%,
      and negative predictive value of 66% at a threshold of 1.272. We conclude that
      ApEn analysis of heart rate data obtained from pulse oximetric recordings could
      be a useful tool in the study of OSA.

PMID- 16450177
TI  - Conflict resolution in an ant-plant interaction: Acacia constricta traits reduce
      ant costs to reproduction.
AB  - Many plant species attract ants onto their foliage with food rewards or nesting
      space. However, ants can interfere with plant reproduction when they visit
      flowers. This study tests whether Acacia constricta separates visiting ant
      species temporally or spatially from newly opened inflorescences and pollinators.
      The diurnal activity patterns of ants and A. constricta pollinators peaked at
      different times of day, and the activity of pollinators followed the daily
      dehiscence of A. constricta inflorescences. In addition to being largely
      temporally separated, ants rarely visited open inflorescences. A floral ant
      repellent contributes to the spatial separation of ants and inflorescences. In a
      field experiment, ants of four species were given equal access to inflorescences
      in different developmental stages. On average, the frequency with which ants made
      initial, antennal contact with the floral stages did not differ, but ants
      significantly avoided secondary contact with newly opened inflorescences relative
      to buds and old inflorescences, and old inflorescences relative to buds. Ants
      also avoided contact with pollen alone, indicating that pollen is at least one
      source of the repellent. The results suggest A. constricta has effectively
      resolved the potential conflict between visiting ants and plant reproduction.

PMID- 16450178
TI  - Consequences of pre-dispersal damage by insects for the dispersal and recruitment
      of mangroves.
AB  - Herbivores may enhance plant recruitment, but such positive interactions may be
      overlooked in favour of obvious negative effects of herbivory on propagules. My
      objective was to determine whether larval insects that feed and develop within
      fruit of the mangrove Avicennia marina act as mutualist herbivores by increasing
      the dispersal of propagules without affecting their viability and emerging
      successfully as adults following dispersal of the propagule by water. Surveys
      revealed that frugivory is common throughout the mangrove forest, and fruit had
      up to six exit holes where larvae had emerged as adults. Larval insects did not
      affect the flotation of propagules with pericarps, a thin structure that provides
      buoyancy for dispersal by water. In contrast, after simulating germination by
      removing the pericarp, the majority of propagules with three exit holes floated
      on average for 20 h longer than those without exit holes, which sank immediately.
      Based on this evidence that frugivory could increase the dispersal potential of
      propagules, I predicted that propagules consumed by larval insects should
      disperse farther than undamaged propagules, and this was tested by quantifying
      the potential viability of propagules stranded on beaches at increasing distances
      (up to 20 km) from mangrove forests. Flies and moths emerged as adults after
      being transported tens of kilometres within mangrove propagules, revealing a
      novel mode of dispersal. Proportionally fewer potentially viable propagules were
      supplied to beaches at increasing distances from mangrove forests, however,
      indicating that larval insects negatively affect recruitment and are thus not
      acting as mutualist herbivores. Nevertheless, when transported back to the
      mangrove forest, seedlings established from propagules damaged by larval insects
      and stranded on beaches. Therefore, although frugivory does not preclude mangrove
      recruitment, its negative effects in the pre-dispersal environment may be
      intensified with increasing dispersal distance, thus limiting the long-distance
      supply of propagules and recruitment of mangroves.

PMID- 16450179
TI  - Limitations to seedling establishment in a mesic Hawaiian forest.
AB  - While invasive species may be visible indicators of plant community degradation,
      they may not constitute the only, or even the primary, limitation to stand
      regeneration. We used seed-augmentation and grass-removal experiments under
      different canopy conditions to assess the relative importance of dispersal
      limitation, resource availability, and competition on seedling establishment in
      the understory shrubs Sophora chrysophilla, Dodonea viscosa, and Pipturus albidus
      in a montane mesic forest in Hawaii. The study location was an Acacia koa
      Metrosideros polymorpha forest at 1000-1500 m elevation on the leeward side of
      Hawaii Island; it is a closed-canopy forest historically subject to logging and
      grazing by cattle and sheep and currently dominated by the exotic grass, Ehrharta
      stipoides, in the herb layer. Seedling establishment after 1 and 2 years was
      strongly dispersal limited in Sophora and Dodonea, but not in Acacia, a non
      augmented species in which abundant seedlings established, nor in Pipterus, in
      which only one seedling established in 2 years. Grass cover reduced seedling
      establishment in Acacia, Sophora, and Dodonea and, for the latter two species,
      seedling establishment was substantially greater in the warmer, more moist forest
      at the lowest elevation. Light, moisture, and resin-captured N and P were more
      strongly affected by elevation and canopy composition than by grass cover, but in
      most cases seedling establishment was not positively correlated with resource
      availability. Limitations to the establishment of woody seedlings in this forest
      grassland mixture vary among species; however, both dispersal limitation and
      competition from a shade-tolerant grass are important deterrents to regeneration
      in these forests.

PMID- 16450180
TI  - Strengthened insectivory in a temperate fragmented forest.
AB  - Habitat fragmentation modifies ecological patterns and processes through changes
      in species richness and abundance. In the coastal Maulino forest, central Chile,
      both species richness and abundance of insectivorous birds increases in forest
      fragments compared to continuous forest. Through a field experiment, we examined
      larvae predation in fragmented forests. Higher richness and abundance of birds
      foraging at forest fragments translated into more insect larvae preyed upon in
      forest fragments than in continuous forest. The assessed level of insectivory in
      forest fragments agrees with lower herbivory levels in forest fragments. This
      pattern strongly suggests the strengthening of food interactions web in forest
      fragments of coastal Maulino forest.

PMID- 16450182
TI  - A continental scale evaluation of the role of limpet grazing on rocky shores.
AB  - It is critical for our knowledge of biodiversity and ecosystem processes to
      understand how individual species contribute to ecosystem processes and how these
      contributions vary in space and time. We used a manipulative field experiment in
      five locations over 17 degrees of latitude [from southern Portugal to the Isle of
      Man (British Isles)] to determine the relative response of rocky intertidal algal
      assemblages released from control by the grazing of limpets. Response ratios
      showed that when limpets were removed there was a trend of effects from north to
      south. In the north, grazing had a strong effect on algal assemblages, but
      removing grazers reduced spatial variability in assemblages. In the south, the
      effect of limpet grazing was far weaker and removal of grazers had a much reduced
      impact on spatial variability. Here we show a clear trophic control of an
      ecosystem in that grazing by limpets not only determines macroalgal abundance
      overall but also modifies ecosystem stability via variability in cover of algae.

PMID- 16450181
TI  - Investment in immune defense is linked to pace of life in house sparrows.
AB  - The evidence for a relationship between life history and immune defense is
      equivocal, although the basic premise is intuitively appealing: animals that live
      short lives and reproduce early and rapidly should not waste resources on
      defenses they might never use. One possible reason for a lack of strong support
      for this hypothesis could be the inherent complexity of the vertebrate immune
      system. Indeed, different components of the vertebrate immune system vary in
      their relative costs and benefits, and therefore only some defenses may
      complement variation in species' life history. To address this hypothesis, we
      compared multiple types of immune activity between two populations of house
      sparrows (Passer domesticus) with distinct life histories, one from Colon,
      Panama, which lay small clutches over an extended breeding season (i.e., slow
      living) and the other from Princeton, New Jersey, which lay larger clutches in a
      smaller window of time (i.e., fast-living). We expected (a) that more costly
      types of immune defenses would be stronger in the slow-living sparrows and (2)
      that the slow-living sparrows would show a greater increase in whole-body energy
      expenditure after immune challenge compared to their fast-living counterparts. We
      found that secondary antibody response to a novel antigen was more rapid and
      energetic investment in immune activity was greater in slow-living sparrows.
      However, cell-mediated immune activity was more robust in fast-living sparrows,
      and other measures of defense were not different between populations. These
      results provide partial support for a relationship between life history and
      immune defense in this species, but they also indicate that this relationship is
      not clear-cut. Further study is necessary to identify the influence of other
      factors, particular pathogen environment during development, on the architecture
      of the immune system of wild animals.

PMID- 16450183
TI  - Molecular tagging of stripe rust resistance gene YrZH84 in Chinese wheat line
      Zhou 8425B.
AB  - Stripe rust, caused by Puccinia striiformis f. sp. tritici (PST), is one of the
      most damaging diseases in common wheat (Triticum aestivum L.). With the objective
      of identifying and tagging new genes for resistance to stripe rust, F1, F2 and F3
      populations from the cross Zhou 8425B/Chinese Spring were inoculated with Chinese
      PST isolate CYR32 in the greenhouse. A total of 790 SSR primers were used to test
      the parents and resistant and susceptible bulks. The resulting seven polymorphic
      markers on chromosome 7BL were used for genotyping F2 and F3 populations. Results
      indicated that Zhou 8425B carries a single dominant resistance gene, temporarily
      designated YrZH84, closely linked to SSR markers Xcfa2040-7B and Xbarc32-7B with
      genetic distances of 1.4 and 4.8 cM, respectively. In a seedling test with 25 PST
      isolates, the reaction patterns of YrZH84 were different from those of lines
      carrying Yr2 and Yr6. It was concluded that YrZH84 is probably a new stripe rust
      resistance gene.

PMID- 16450184
TI  - SSR-based linkage map with new markers using an intraspecific population of
      common wheat.
AB  - Simple sequence repeats (SSRs) are valuable molecular markers in many plant
      species. In common wheat (Triticum aestivum L.), which is characteristic of its
      large genomes and alloploidy, SSRs are one of the most useful markers. To
      increase SSR marker sources and construct an SSR-based linkage map of appropriate
      density, we tried to develop new SSR markers from SSR-enriched genomic libraries
      and the public database. SSRs having (GA)n and (GT)n motifs were isolated from
      enriched libraries, and di- and tri-nucleotide repeats were mined from expressed
      sequence tags (ESTs) and DNA sequences of Triticum species in the public
      database. Of the 1,147 primer pairs designed, 842 primers gave accurate
      amplification products, and 478 primers showed polymorphism among the nine wheat
      lines examined. Using a doubled haploid (DH) population from an intraspecific
      cross between Kitamoe and Munstertaler (KM), we constructed an SSR-based linkage
      map that consisted of 464 loci: 185 loci from genomic libraries, 65 loci from the
      sequence database including ESTs, 213 loci from the SSR markers already reported,
      and 1 locus of morphological marker. Although newly developed SSR loci were
      distributed throughout all chromosomes, clustering of them around putative
      centromeric regions was found on several chromosomes. The total length of the KM
      map spanned 3,441 cM and corresponded to approximately 86% genome coverage. The
      KM map comprised of 23 linkage groups because two gaps of over 50 cM distance
      remained on chromosome 6A. This is a first report of SSR-based linkage map using
      single intraspecific population of common wheat. This mapping result suggests
      that it becomes possible to construct linkage maps with sufficient genome
      coverage using only SSR markers without RFLP markers, even in an intraspecific
      population of common wheat. Moreover, the new SSR markers will contribute to the
      enrichment of molecular marker resources in common wheat.

PMID- 16450185
TI  - Locked knee caused by intraarticular ganglion.
AB  - Intraarticular ganglion cyst arising from the cruciate ligament is difficult to
      diagnose by clinical symptom. In our case, Cyst attached anteriorly to posterior
      cruciate ligament, and limited both flexion and extension of knee. The cyst was
      excised in a piecemeal fashion arthroscopically. Knee pain and limitation in knee
      motion disappeared by the day after surgery. We hypothesize that reason of
      restriction of extension is impingement between anterior cruciate ligament and
      intracondylar, and reason of restriction of flexion is stimulation nerve ending
      in the synovial membrane stretched with knee motion.

PMID- 16450186
TI  - Stress relaxation in porcine septal cartilage during electromechanical reshaping:
      mechanical and electrical responses.
AB  - Electromechanical reshaping (EMR) of facial cartilage has recently been developed
      as an alternative to classic surgical techniques to alter cartilage shape. This
      study focuses on determining the underlying physical mechanisms responsible for
      shape change (stress relaxation) in mechanically deformed facial cartilage
      specimens exposed to constant electric fields. Flat porcine nasal septal
      cartilage specimens were deformed by an aluminum jig into semicylindrical shapes
      while a constant electric voltage was applied to the concave and convex surfaces
      of the specimen. Mechanical stress, electric current and resistance were measured
      during voltage application. Specimen shape retention was measured as retained
      bend angle. Total electric charge transferred in the electric circuit was
      calculated from the electric current measurement. Electrical resistance,
      transferred charge and the bend angle increase with increase in voltage
      application time until bend angle reaches maximum value determined by the jig
      geometry. Then, the bend angle decreases and electrical parameters nearly
      saturate. The time dependent behavior of electric current was analyzed using the
      Cottrell equation. The observed changes in electric current suggest that during
      the initial 1-2 min of EMR nonlinear diffusion determines electro-chemical
      reaction rates, which are then followed by a linear diffusion dominated process.
      Close correlation between alteration of cartilage mechanical state and change in
      its electrical properties suggest that an electro-chemical reaction is the
      dominant mechanism behind EMR.

PMID- 16450187
TI  - Numerical solution of ocular fluid dynamics in a rabbit eye: parametric effects.
AB  - Numerical calculations of the aqueous humor dynamics in the anterior chamber of a
      rabbit's eye are presented to delineate the basic flow mechanisms. The
      calculations are based on a geometrical model of the eye, which represents the
      Trabecular meshwork (TM) as a multilayered porous zone of specified pore sizes
      and void fraction. The outer surface of the cornea is assumed to be at a fixed
      temperature (corresponding to the ambient temperature), while the iris surface is
      assumed to be at the core body temperature. Results are obtained for both the
      horizontal upward-facing orientation of the eye, and the vertical orientation of
      the eye. Parameters varied include: the temperature difference between the iris
      and the cornea to underscore the important role of buoyancy in driving the
      aqueous humor flow; and, the pupil size reflecting different levels of ambient
      light. Buoyancy is observed to be the dominant driving mechanism for the
      convective motion in both orientations of the eye. Variations in the pupil size
      appear to have little influence on the IOP or flow distribution in view of the
      dominant role of buoyancy in controlling the flow motion. The study provides
      distributions of the shear stress and flow patterns and delineates the important
      role of the eye-orientation on these results.

PMID- 16450188
TI  - Slow-fast decoupling of the disparity convergence eye movements dynamics.
AB  - In this paper we show how to separate the slow and fast dynamics of the disparity
      convergence of the eye movements dynamic model. The dynamic equations obtained
      determine the modified slow dynamics that takes into account the impact of the
      fast dynamics and the modified fast dynamics that takes into account the impact
      of the slow dynamics. The slow fast decoupling is achieved by finding analytical
      solutions of the transformation equations used. The transformed slow and fast
      subsystems have very simple forms. Having separated the slow and fast dynamics
      completely, neural control problems for the slow and fast eye movements dynamics
      can be independently studied and better understood.

PMID- 16450189
TI  - Education for careers in tissue engineering and regenerative medicine.

PMID- 16450191
TI  - Undergraduate biomedical imaging education.

PMID- 16450190
TI  - The undergraduate biomedical engineering curriculum: devices and instruments.

PMID- 16450192
TI  - Online prediction of onsets of seizure-like events in hippocampal neural networks
      using wavelet artificial neural networks.
AB  - It has been previously shown that wavelet artificial neural networks (WANNs) are
      able to classify the different states of epileptiform activity and predict the
      onsets of seizure-like events (SLEs) by offline processing (Ann. Biomed. Eng.
      33(6):798-810, 2005) of the electrical data from the in-vitro hippocampal slice
      model of recurrent spontaneous SLEs. The WANN design entailed the assumption that
      time-varying frequency information from the biological recordings can be used to
      estimate the times at which onsets of SLEs would most likely occur in the future.
      Progressions of different frequency components were captured by the artificial
      neural network (ANN) using selective frequency inputs from the initial wavelet
      transform of the biological data. The training of the WANN had been established
      using 184 SLE episodes in 34 slices from 21 rats offline. Nine of these rats also
      exhibited periods of interictal bursts (IBs). These IBs were included as part of
      the training to help distinguish the difference in dynamics of bursting
      activities between the preictal- and interictal type. In this paper, we present
      the results of an online processing using WANN on 23 in-vitro rat hippocampal
      slices from 9 rats having 93 spontaneous SLE episodes generated under low
      magnesium conditions. Over the test cases, three of the nine rats exhibited over
      30 min of IB activities. We demonstrated that the WANN was able to classify the
      different states, namely, interictal, preictal, ictal, and IB activities with an
      accuracy of 86.6, 72.6, 84.5, and 69.1%, respectively. Prediction of state
      transitions into ictal events was achieved using regression of initial
      "normalized time-to-onset" estimates. The SLE onsets can be estimated up to 36.4
      s ahead of their actual occurrences, with a mean error of 14.3 +/- 27.0 s. The
      prediction errors decreased progressively as the actual time-to-onset decreased
      and more initial "normalized time-to-onset" estimates were used for the
      regression procedure.

PMID- 16450193
TI  - Biaixal stress-stretch behavior of the mitral valve anterior leaflet at
      physiologic strain rates.
AB  - Characterization of the mechanical properties of the native mitral valve leaflets
      at physiological strain rates is a critical step in improving our understanding
      of MV function and providing experimental data for dynamic constitutive models.
      We explored, for the first time, the effects of strain rate (from quasi-static to
      physiologic) on the biaxial mechanical properties of the native mitral valve
      anterior leaflet (MVAL). A novel high-speed biaxial testing device was developed,
      capable of achieving in vitro strain rates reported for the MVAL (Sacks et al.,
      Ann. Biomed. Eng. 30(10):1280-1290, 2002). Porcine MVAL specimens were loaded to
      physiological load levels with cycle periods of 15, 1, 0.5, 0.1, and 0.05 s. The
      resulting loading stress-strain responses were found to be remarkably independent
      of strain rate. The hysteresis, defined as the fraction of the membrane strain
      energy between the loading and unloading curves tension-areal stretch curves, was
      low (approximately 12%) and did not vary with strain rate. The results of the
      present work indicated that MVAL tissues exhibit complete strain rate
      insensitivity at and below physiological strain rates under physiological loading
      conditions. These novel results suggest that experimental tests utilizing quasi
      static strain rates are appropriate for constitutive model development for mitral
      valve tissues. The mechanisms underlying this quasi-elastic behavior are as yet
      unknown, but are likely an important functional aspect of native mitral valve
      tissues and clearly warrant further study.

PMID- 16450194
TI  - Long-range correlations in rabbit brain neural activity.
AB  - We have analyzed the presence of persistence properties in rabbit brain
      electrical signals by means of non-equilibrium statistical physics tools. To
      measure long-memory properties of these experimental signals, we have first
      determined whether the data are fractional Gaussian noise (fGn) or fractional
      Brownian motion (fBm) by calculating the slope of the power spectral density plot
      of the series. The results show that the series correspond to fBm. Then, the data
      were studied by means of the bridge detrended scaled windowed variance analysis,
      detecting long-term correlation. Three different types of experimental signals
      have been studied: neural basal activity without stimulation, the response
      induced by a single flash light stimulus and the average of the activity evoked
      by 200 flash light stimulations. Analysis of the series revealed the existence of
      persistent behavior in all cases. Moreover, the results also exhibited an
      increasing correlation in the level of long-term memory from recordings without
      stimulation, to one sweep recording or 200 sweeps averaged recordings. Thus,
      brain neural electrical activity is affected not only by its most recent states,
      but also by previous states much more distant in the past.

PMID- 16450195
TI  - Drug delivery in the BME curricula.

PMID- 16450196
TI  - Teaching cellular engineering.
AB  - Cellular engineering is one of the fastest growing subdisciplines in the field of
      Biomedical Engineering. It involves the application of engineering analysis to
      understand and control cellular behavior, with the ultimate objective of
      developing novel therapeutic or diagnostic approaches for the clinic or
      harnessing cellular function for commercial applications. Well-educated students
      in this area need strong foundational knowledge in engineering science,
      chemistry, and cell and molecular biology. In undergraduate curricula, the
      challenge is to include essential engineering skills plus appropriate levels of
      training in chemistry and biology while satisfying accreditation-mandated breadth
      in engineering training. At the graduate level, educators must accommodate
      students with diverse backgrounds and provide them with both a state-of-the-art
      understanding of the life sciences and the most advanced engineering skills.
      Engineering curricular content should include mechanics and materials, physical
      chemistry, transport phenomena, and control theory. Training from faculty with
      appointments and research programs in the life sciences is generally recommended,
      and additional life science content should also be integrated within the
      engineering curriculum. A capstone course in cellular engineering that includes
      opportunities for students to have hands-on experiences with state-of-the-art
      laboratory techniques is highly recommended.

PMID- 16450197
TI  - White paper: Rationale, goals, and approach for education of biosystems and
      biosignals in undergraduate biomedical engineering degree programs.

PMID- 16450198
TI  - Neuronal electrical rhythms described by composite mapped clock oscillators.
AB  - The Mapped Clock Oscillator (MCO) model is a representation of omnipresent
      transmembrane voltage oscillations in excitable cells. We present a generalized
      version of the MCO that can model neuronal electrical oscillations, both labile
      and omnipresent, entirely within the framework of a system of ordinary
      differential equations. The previously described MCO was a second-order system,
      whereas the model presented here, which we call the composite MCO (cMCO) is a
      fourth-order system. Furthermore, we show how this cMCO can also be adapted to
      describe a pair of cells that forms a functional unit, as illustrated here by a
      model of the CA3 pyramidal cell and its basket cell interneuron feedback loop.
      The model was able to reproduce the high frequencies (super gamma) and possibly
      chaotic dynamics observed in the biological system.

PMID- 16450199
TI  - Engineering luminescent quantum dots for in vivo molecular and cellular imaging.
AB  - Semiconductor quantum dots are luminescent nanoparticles that are under intensive
      development for use as a new class of optical imaging contrast agents. Their
      novel properties such as optical tunability, improved photostability, and
      multicolor light emission have opened new opportunities for imaging living cells
      and in vivo animal models at unprecedented sensitivity and spatial resolution.
      Combined with biomolecular engineering strategies for tailoring the particle
      surfaces at the molecular level, bio-conjugated quantum dot probes are well
      suited for imaging single-molecule dynamics in living cells, for monitoring
      protein-protein interactions within specific intracellular locations, and for
      detecting diseased sites and organs in deep tissue. In this article, we describe
      the engineering principles for preparing high-quality quantum dots and for
      conjugating the dots to biomolecular ligands. We also discuss recent advances in
      using quantum dots for in vivo molecular and cellular imaging.

PMID- 16450201
TI  - Differential evolution of mortality between Denmark and Scotland, period 1970 to
      1999. A comparison with mortality data from the European Union.
AB  - Mortality rates in Denmark and Scotland are high compared to rates of the other
      countries of the European Union (EU). Moreover, the evolution of mortality
      between 1970 and 1999 is very different between the two countries. Differences in
      lifestyle as possible explanations have been explored. Mortality rates from all
      causes, total cardiovascular, total cancer and lung cancer for both sexes and
      from female breast cancer were provided by WHO. Food supply data have been
      obtained from FAO and smoking rates from published data. Risk factor distribution
      has been obtained from the Monica survey. The initial mortality was high in both
      countries for all diseases explored, but highest in Scotland. Progressively the
      mortality rates between Scotland and Denmark have equalized, especially due to a
      more rapid decrease of mortality in Scotland. The decrease in all-cause
      mortality, both in Scotland, Denmark and the EU is almost exclusively due to a
      decrease of non-cancer mortality, especially TCV mortality. In conclusion,
      changes in smoking habits and in animal (saturated) fat intake, more pronounced
      in Scotland, offer the best explanation for the observed changes in mortality.
      Smoking and nutrition appear to be the most important determinants of mortality
      in industrialized countries.

PMID- 16450202
TI  - Analysis of the benefits of a Mediterranean diet in the GISSI-Prevenzione study:
      a case study in imputation of missing values from repeated measurements.
AB  - The problem of missing values has increasingly being recognized in epidemiology.
      New methods allow for the analysis of missing data that can provide valid
      estimates of epidemiological quantities of interest. The GISSI-Prevenzione study
      was aimed to reliably assess the long-term relationship between the consumption
      of foods typical of the Mediterranean diet and the risk of mortality amongst
      11,323 Italians with prior myocardial infarction. Food intake frequencies were
      recorded repeatedly over the 4.5 years of follow-up and missing values affected
      each food variable at increasing rates over the course of the study. Comparisons
      were made between the results obtained from the analysis of the complete data and
      those obtained after imputing the missing data with simple imputation methods and
      with various implementations of the multiple imputation (MI) method. MI appeared
      to best address the issue of missing data on the food intake frequencies,
      preserving the observed distributions and relationships between variables whilst
      producing plausible estimates of variability. Given its theoretical properties
      and flexibility to different types of data, MI is more likely to provide valid
      estimates, compared to complete data analysis and imputation by simple methods,
      and is thus worthy of wider consideration amongst epidemiological researchers.

PMID- 16450203
TI  - Characteristics and analysis of risk factors for mortality in infective
      endocarditis.
AB  - OBJECTIVE: The aim of our study was to establish the etiology of and risk factors
      for infective endocarditis (IE) and determine the prognostic factors for adverse
      outcome during hospital admission in a Turkish population. MATERIAL AND METHODS:
      Between January 2002 and January 2004, the clinical and laboratory features of
      112 consecutive adult patients (>18 years) with diagnosis of IE who were referred
      to the infectious diseases clinics/departments of 17 teaching hospitals in Turkey
      were evaluated. Cases of IE were defined according to the modified Duke Criteria.
      Mortality was defined as death occurring within 30 days or during hospital stay
      period. Univariate and multivariate analyses were performed to predict the
      factors related to fatal outcome. RESULTS: A total of 112 consecutive patients
      presented with 101 definite and 11 probable IE episodes were defined according to
      the modified Duke Criteria. The mean age was 45.2+/-19.9. Fifty percent of the
      patients were male. Ninety (60.4%) of the 112 patients had risk factors for IE
      and 48 (42.9%) of them had >or=2 risk factors. On the other hand, 49.1% of
      patients had cardiac risk factors. Blood cultures were positive in 94 (83.9%)
      cases. Staphylococci were the most common agents (50.0%), followed by
      streptococci (28.7%) and enterococci (16.0%). Native cardiac valves were detected
      in 93 (83%) of the episodes of suspected IE. Valvular involvement was present in
      103 (92%) patients; the mitral valve, alone or in combination with other valves,
      was affected in 70 (62.5%) of the patients. Echocardiography detected vegetations
      in 105 patients (93.8%). The mortality rate was 28.6%. Three factors were
      independently associated with mortality: haemodialysis OR: 14.5 (95% CI: 1.5
      138.2), mobile vegetation OR: 4.8 (95% CI: 1.5-15.4) and mental alteration OR:
      4.1 (95% CI: 1.1-15.6). CONCLUSION: Mortality is still high in IE. Our data
      indicate that patients with altered mental status, mobile vegetation, or on
      haemodialysis had poorer prognosis.

PMID- 16450204
TI  - Birth size and coronary heart disease risk score in young adulthood. The
      Atherosclerosis Risk in Young Adults (ARYA) study.
AB  - Data of the Atherosclerosis Risk in Young Adults (ARYA) study were used to
      investigate the association between birth size and the absolute risk for coronary
      heart disease in healthy young adults. The cohort study comprises 750 (46.9% men)
      subjects born between 1970 and 1973. Birth characteristics were obtained from
      school health records. At young adulthood, blood pressure, anthropometry and
      fasting lipid levels were measured. Questionnaires were taken about smoking and
      diabetes. The young adult 10-year risk for coronary heart disease was calculated
      using the Framingham risk score. The overall 10-year risk for coronary heart
      disease was 1.6% (standard deviation (SD) 1.9), 3.0% (SD 1.9) in men and 0.3% (SD
      0.2) in women. Using linear regression it was shown that a SD lower birth weight
      (=0.54 kg) was associated with 0.1% greater risk in the overall population (95%
      confidence interval (CI): -0.19, -0.004). Similarly, a lower ponderal index at
      birth was associated with an 0.11% higher risk (95% CI: -0.21, -0.002). These
      relations were stronger in men. Lower birth length was related with an increased
      risk in women (-0.02% risk/SD birth length; 95% CI: -0.04, 0.0001). These results
      suggest that small birth size is associated with an increased risk score for
      coronary artery disease in young adulthood.

PMID- 16450206
TI  - Evaluation of the cumulative evidence for freedom from BSE in birth cohorts.
AB  - Substantial resources are used for surveillance of bovine spongiform
      encephalopathy (BSE) despite an extremely low detection rate, especially in
      healthy slaughtered cattle. We have developed a method based on the geometric
      waiting time distribution to establish and update the statistical evidence for
      BSE-freedom for defined birth cohorts using continued surveillance data. The
      results suggest that currently (data included till September 2004) a birth cohort
      of Danish cattle born after March 1999 is free from BSE with probability (power)
      of 0.8746 or 0.8509, depending on the choice of a model for the diagnostic
      sensitivity. These results apply to an assumed design prevalence of 1 in 10,000
      and account for prevalence heterogeneity. The age-dependent, diagnostic
      sensitivity for the detection of BSE has been identified as major determinant of
      the power. The incorporation of heterogeneity was deemed adequate on scientific
      grounds and led to improved power values. We propose our model as a decision tool
      for possible future modification of the BSE surveillance and discuss public
      health and international trade implications.

PMID- 16450205
TI  - A geographic correlation study of the incidence of pancreatic and other cancers
      in Whites.
AB  - Ecologic analyses of cancer incidence rates may be helpful to formulate
      hypotheses on risk factors and mechanisms of poorly known neoplasms, such as
      pancreatic cancer. We calculated sex-specific pair-wise and partial (after
      adjustment for lung cancer incidence) correlations between the incidence of
      pancreatic cancer and that of 23 other cancers in two international sets of
      cancer incidence data: the recorded or estimated incidence for 2000 in 38
      European countries and the recorded incidence in Whites for 1993-1997 in 35
      cancer registries from North America and Oceania. In both sexes and datasets, a
      strong, highly significant correlation was present between the incidence of
      pancreatic cancer and that of lung and kidney cancer. For the latter, correlation
      coefficients in the European data were 0.71 in men and 0.74 in women (both
      p<0.0001); in the cancer registry data they were 0.57 (p=0.0004) in men and 0.45
      (p=0.007) in women. The results on kidney cancer were not modified by adjustment
      for the correlation with lung cancer, were confirmed by the application of
      spatial regression models and, with the exception of men in the cancer registry
      data, were confirmed in sensitivity analyses restricted to the populations with
      data of best quality. Weaker, less consistent correlations were found for
      colorectal, endometrial, ovarian and bladder cancers. Tobacco smoking is a
      plausible explanation of the association between pancreatic and lung cancer; the
      association with kidney cancer likely reflects additional common etiologic and
      pathogenetic factors of the two neoplasms.

PMID- 16450207
TI  - Is inflammation a causal chain between low socioeconomic status and type 2
      diabetes? Results from the KORA Survey 2000.
AB  - Low socioeconomic status (SES) is associated with type 2 diabetes. Inflammatory
      markers like C-reactive protein (CRP) are predictive of diabetes. It is unclear,
      whether inflammation may be a mechanism linking low SES to type 2 diabetes. In
      the population-based KORA Survey 2000, 766 men and 710 women aged 55 to 74 years
      were randomly selected in the Augsburg region (Southern Germany). An index for
      SES was defined using education, occupation, and income. In women but not in men,
      increased CRP concentrations were found with lower SES (p<0.01). This significant
      trend was no longer observed after adjusting for BMI and waist circumference
      (p=0.23). Low SES was significantly associated with the age-adjusted odds of
      having type 2 diabetes both in men (OR; 95%CI: 1.35; 1.14-1.60) and in women
      (2.01; 1.37-2.96). The risk of having diabetes associated with low SES was only
      slightly changed after adjusting for CRP, which was itself significantly related
      to diabetes. In multivariate analyses, adjusting for age, obesity, physical
      activity, smoking, alcohol intake, and CRP, low SES yielded only a borderline
      statistical significance in women (p=0.07), whereas no significant association
      with diabetes remained in men (p=0.14). After CRP was dropped from the full
      model, there was no change in the OR obtained for low SES (men: 1.30; 0.92-1.83;
      women: 1.54; 0.97-2.45). Low SES was not related to prediabetes (IFG, IGT),
      whereas CRP was significantly associated with diabetes precursors. In conclusion,
      inflammation appears not to play a major role linking low SES and type 2 diabetes
      in the elderly population.

PMID- 16450208
TI  - Did the 1991-1995 wars in the former Yugoslavia affect sex ratio at birth?
AB  - Proportion of males at birth (commonly referred to as the sex ratio) has been
      investigated for countries of former Yugoslavia that were affected by the 1991
      1995 wars. Number of live births for Slovenia, Croatia, Bosnia and Herzegovina
      with Serbian Republic, and Serbia and Montenegro were obtained from the official
      vital statistics data and analysed with the Chi-square test. Results yielded no
      difference in the sex ratio associated with the war for the entire data set.
      However, country level data analysis revealed a significant increase in Bosnia
      and Herzegovina with the Serbian Republic, where proportion of male births during
      the wartime reached as high as 0.523 (compared to 0.516 in the pre-war and 0.515
      in the post-war period). Countries that were involved in either mild or
      intermediate level of warfare did not exhibit a significant increase in the sex
      ratio (e.g. Slovenia and Croatia). Although war in Croatia lasted a year longer
      than in Bosnia and Herzegovina, analysis of the most intensive wartime periods in
      Croatia did not yield significant change. It seems that a hypothetical threshold
      of the warfare intensity combined with duration has to be reached (e.g. as in
      case of Bosnia and Herzegovina), in order for war to influence the sex ratio.

PMID- 16450209
TI  - Population-based case-control study of the common cold during pregnancy and
      congenital abnormalities.
AB  - The common cold is the most frequent maternal disease during pregnancy. The
      possible association between different congenital abnormalities and the common
      cold in pregnant women was evaluated in the data set of the Hungarian Case
      Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 22,843
      cases with congenital abnormalities, 3,827 (16.8%) had mothers with the common
      cold, while of 38,151 population controls without congenital abnormalities, 5,475
      (14.4%) (adjusted prevalence odds ratio: POR: 1.26 with 95% CI: 1.20-1.32). Of
      834 malformed controls with Down syndrome, 114 (17.3%) had mothers with the
      common cold (POR: 0.96 with 95% CI: 0.80-1.16). Nearly half of mothers with the
      common cold had secondary complications with antifever therapy. The comparison of
      cases with 25 congenital abnormalities and population control mothers with
      medically recorded common cold during the second and third months of gestation
      showed that five congenital abnormality groups: congenital hydrocephaly (3.6, 1.3
      9.7), cleft lip+/-palate (2.3, 1.5-3.6), posterior cleft palate (2.3, 1.2-4.1),
      limb deficiencies (2.2, 1.1-4.1) and multiple CAs (2.0, 1.4-2.9) had adjusted POR
      2 or more. The comparison of cases with different congenital abnormalities and
      malformed controls (including offspring with Down syndrome) as referent,
      indicated a higher prevalence of the common cold during the second and third
      month of gestation only in the mothers of cases with cleft lip+/-palate (adjusted
      POR: 1.7 with 95% CI: 1.2-2.5), however, congenital hydrocephaly, neural-tube
      defects and multiple CAs had also mothers with a somewhat higher occurrence of
      the common cold. The possible association between the common cold during early
      pregnancy and the above mentioned congenital abnormalities may be connected
      mainly with the indirect effect of secondary complications of maternal common
      cold, particularly high fever because antifever drugs were able to prevent the
      possible teratogenic effect of the common cold.

PMID- 16450210
TI  - Seroprevalence of anti-Yersinia antibodies in healthy Austrians.
AB  - Yersiniosis is caused by Y. enterocolitica and Y. pseudotuberculosis mostly
      presenting as intestinal infection. The infection is usually acquired from
      contaminated food. The aim of this study was to determine the seroprevalence of
      anti-Yersinia antibodies in Austrians. Sera of 750 healthy Austrians from all
      nine states were tested for anti-Yersinia IgG antibodies using the recomBlot
      Yersinia Westernblot kit. Overall seroprevalence was 29.7%. Seroprevalence
      increased significantly with age from 24.7% in the group of the 19 to 24 year
      olds to 38.5% in the group of persons older than 44 years. The seroprevalence of
      anti-Yersinia antibodies varied within the states between 18% and 43.5%. The high
      seroprevalence of anti-Yersinia antibodies in contrast to only approximately 100
      reported yersiniosis cases per year points to the fact that the majority of
      infections is either subclinical or mild.

PMID- 16450211
TI  - Long-term outcome and quality of life after continent ileostomy.
AB  - INTRODUCTION: This study was designed to evaluate long-term outcomes for patients
      undergoing Kock continent ileostomy, identify factors associated with adverse
      outcomes, and compare changes in quality of life after removal of the reservoir.
      METHODS: The records of all patients (n = 330) undergoing continent ileostomy at
      the Cleveland Clinic Foundation between 1974 and 2001 were reviewed. Patient
      related, intraoperative, and postoperative factors were evaluated as predictor
      variables of long-term pouch survival. Quality of life was evaluated using the
      continent ileostomy surgery follow-up questionnaire and the Cleveland Global
      Quality of Life scale (n = 216). These were compared between patients with
      continent ileostomy (n = 181) and patients who underwent removal of the continent
      ileostomy and conversion to an end stoma (n = 35). RESULTS: The median patient
      follow-up was 11 (range, 1-27) years. The median revision-free pouch interval was
      14 (95 percent confidence interval, 11-17) months. The 10-year and 20-year pouch
      survival was 87 and 77 percent, respectively. Patients had an average of
      3.7(range, 1-28) complications and 2.9 (range, 1-27) pouch revisions during
      follow-up. On multivariate analysis, Crohn's disease (hazard ratio = 4.5), female
      gender (hazard ratio = 2.4), fistula development (hazard ratio = 3), and body
      mass index (hazard ratio = 2.4 per 5 unit increase) were independent predictors
      of pouch failure. Quality of life measurements for patients with a continent
      ileostomy were higher on all scales in comparison with patients who had the Kock
      reservoir and then reverted to a Brooke ileostomy. CONCLUSIONS: Despite the
      associated morbidity with continent ileostomy surgery, long-term results and
      quality of life were encouraging. Continent ileostomy may be offered as an
      attractive long-term option to select patients whose only alternative is an end
      ileostomy.

PMID- 16450212
TI  - Imaging techniques contribute to increased surgical rescue of relapse in the
      follow-up of colorectal cancer.
AB  - PURPOSE: This study analyzes the results of a follow-up policy in colorectal
      cancer at our institution and evaluates the possible benefit provided by each
      test performed. PATIENTS AND METHODS: Six hundred nineteen patients who had
      radical surgery and adjuvant treatment for colorectal cancer were followed up
      with a protocol that included carcinoembryonic antigen testing and clinical
      examination every three months for the first two years, every four months in the
      third year, and every six months in the fourth and fifth years. Chest X-ray and
      colonoscopy were performed yearly for five years and abdominal ultrasound was
      done every six months for the first three years and yearly afterward.
      Abdominopelvic computerized tomography was performed yearly for the first two
      years in cases with rectal cancer. If relapse was detected, all operable cases
      underwent surgery if possible. RESULTS: Between 1993 and 1999, 619 patients were
      followed-up. Mean follow-up was 66.9 months. Two hundred eight relapses were
      detected, 83.6 percent in the first three years and 73 (35.1 percent) underwent
      surgical resection. Carcinoembryonic antigen testing detected 44.2 percent of
      recurrences and 31.9 percent of them were operated on. Imaging techniques
      detected a lower percentage of recurrences (18.7 percent) but were more often
      resectable: 52 percent and 60 percent of the recurrences detected by computerized
      tomography and chest X-ray, respectively, underwent surgery. Median overall
      survival of patients with resected relapse was 62 months, significantly higher
      than those who were not operable (12.4 months). CONCLUSION: Imaging techniques in
      the surveillance of resected colorectal cancer contribute to early detection of
      relapse with a high proportion of operable metastatic disease.

PMID- 16450213
TI  - Acoustic to electric pitch comparisons in cochlear implant subjects with residual
      hearing.
AB  - The aim of this study was to assess the frequency-position function resulting
      from electric stimulation of electrodes in cochlear implant subjects with
      significant residual hearing in their nonimplanted ear. Six cochlear implant
      users compared the pitch of the auditory sensation produced by stimulation of an
      intracochlear electrode to the pitch of acoustic pure tones presented to their
      contralateral nonimplanted ear. Subjects were implanted with different Clarion
      electrode arrays, designed to lie close to the inner wall of the cochlea. High
      resolution radiographs were used to determine the electrode positions in the
      cochlea. Four out of six subjects presented electrode insertions deeper than 450
      degrees . We used a two-interval (one acoustic, one electric), two-alternative
      forced choice protocol (2I-2AFC), asking the subject to indicate which stimulus
      sounded the highest in pitch. Pure tones were used as acoustic stimuli. Electric
      stimuli consisted of trains of biphasic pulses presented at relatively high rates
      [higher than 700 pulses per second (pps)]. First, all electric stimuli were
      balanced in loudness across electrodes. Second, acoustic pure tones, chosen to
      approximate roughly the pitch sensation produced by each electrode, were balanced
      in loudness to electric stimuli. When electrode insertion lengths were used to
      describe electrode positions, the pitch sensations produced by electric
      stimulation were found to be more than two octaves lower than predicted by
      Greenwood's frequency-position function. When insertion angles were used to
      describe electrode positions, the pitch sensations were found about one octave
      lower than the frequency-position function of a normal ear. The difference found
      between both descriptions is because of the fact that these electrode arrays were
      designed to lie close to the modiolus. As a consequence, the site of excitation
      produced at the level of the organ of Corti corresponds to a longer length than
      the electrode insertion length, which is used in Greenwood's function. Although
      exact measurements of the round window position as well as the length of the
      cochlea could explain the remaining one octave difference found when insertion
      angles were used, physiological phenomena (e.g., stimulation of the spiral
      ganglion cells) could also create this difference. From these data, analysis
      filters could be determined in sound coding strategies to match the pitch
      percepts elicited by electrode stimulation. This step might be of main importance
      for music perception and for the fitting of bilateral cochlear implants.

PMID- 16450215
TI  - The N ratio predicts recurrence and poor prognosis in patients with node-positive
      early gastric cancer.
AB  - BACKGROUND: The metastatic status of the regional node is the most significant
      prognostic factor for early gastric cancer (EGC). However, diverse prognoses are
      evident even among the same N classifications of the current tumor-node
      metastasis system. The aim of this study was to evaluate the prognostic
      significance of the ratio of metastatic to retrieved lymph nodes (N ratio) in
      identifying a high-risk subgroup with node-positive EGC. METHODS: From a
      prospective database of 1264 EGC patients between 1987 and 1997, 156 (12.4%) were
      found to have histologically confirmed node metastasis. A number of prognostic
      factors, including the N ratio, were evaluated by univariate and multivariate
      analysis. RESULTS: The recurrence rate of node-positive EGC was 16.7% (n = 26).
      The overall 5-year survival rate of all patients was 84.0%. It was 26.9% and
      95.4% in patients with and without recurrence, respectively (P < .0001; log-rank
      test). The cutoff value of the N ratio was set at .07. The 5-year survival rate
      of patients with an N ratio <.07 was 94.0%; this was significantly higher than
      the rate (72.6%) for those with a ratio >.07 (P < .0001; log-rank test). Both
      univariate and multivariate analysis identified the N ratio as the most
      significant predictive factor for recurrence and overall survival. Regarding
      stage migration, it shows superiority in comparison to the number-based N
      classification. CONCLUSIONS: The N ratio is a more effective and rational
      indicator for prognostic stratification of patients with lymph node-positive EGC
      than the current N classification of the tumor-node-metastasis system.

PMID- 16450214
TI  - Protein kinase C family members as a target for regulation of blood-brain barrier
      Na,K,2Cl-cotransporter during in vitro stroke conditions and nicotine exposure.
AB  - PURPOSE: The aim of the study is to identify specific protein kinase C (PKC)
      isoforms involvement in K(+) transport mediated at altered blood-brain barrier
      (BBB) response to stroke conditions with prior nicotine exposure, which provides
      ways to intervene pharmacologically in PKC-mediated molecular pathways that could
      lead to effective treatment for smoking stroke patients. METHODS: Changes in PKC
      isoform levels were studied in the cytosolic and membrane fractions of bovine
      brain microvessel endothelial cells subjected to stroke conditions as well as
      nicotine/cotinine exposure. Furthermore, abluminal Na,K,2Cl-cotransporter (NKCC)
      activity regulated by specific conventional PKC isoform activators and inhibitors
      was investigated using rubidium ((86)Rb) uptake studies. RESULTS: Membrane-bound
      PKCalpha, PKCbetaI, and PKCepsilon levels were increased after 6 h
      hypoxia/aglycemia, and this was attenuated by 24-h nicotine/cotinine exposure.
      Interestingly, membrane-bound PKCgamma protein level was decreased after 6 h
      hypoxia/aglycemia and increased by 24-h nicotine/cotinine exposure. (86)Rb uptake
      studies showed that basolateral NKCC activity was down-regulated by both a
      conventional PKC inhibitor and specific inhibitors for PKCalpha, PKCbeta, and
      PKCvarepsilon and was up-regulated by an activator of conventional PKCs during 6
      h hypoxia/aglycemia treatment. CONCLUSION: Specific PKC inhibitors or activators
      might be designed to individualize stroke therapies and improve health outcome
      for smokers by rebalancing ion transport into and out of the brain.

PMID- 16450216
TI  - Surgery in the era of gene expression profiling-based prediction and
      individualized, neoadjuvant breast cancer therapy: the beginning of the end?

PMID- 16450217
TI  - The growing pains of neoadjuvant trials for gastroesophageal carcinoma.

PMID- 16450218
TI  - The practical value of prediction: a semireliable assistant.

PMID- 16450219
TI  - Chemotherapy and radiotherapy in the treatment of resectable non-small-cell lung
      cancer.
AB  - BACKGROUND: Surgical resection remains the cornerstone of therapy for early-stage
      disease and offers the best chance for cure. Local and distant failure rates,
      however, remain unacceptably high with surgery alone. Radiation and systemic
      chemotherapy have been used to reduce recurrences in early-stage disease.
      Neoadjuvant and adjuvant strategies both offer sound theoretical benefit, but
      evidence supporting this has been lacking. The publication of a meta-analysis in
      1995 triggered a reevaluation of adjuvant chemotherapy. Four randomized trials
      reported in the last 2 years support the use of adjuvant platinum-based
      chemotherapy. METHODS: This article reviews the history of clinical trials
      evaluating neoadjuvant and adjuvant therapy in non-small-cell lung cancer.
      RESULTS: Adjuvant chemotherapy improves 5-year survival rates by approximately 5%
      15% compared with surgery alone. CONCLUSIONS: Surgical resection followed by
      adjuvant chemotherapy is the standard of care treatment for patients with
      completely resected stage I, II, and IIIA non-small-cell lung cancer.

PMID- 16450220
TI  - Laparoscopic versus open surgery for rectal cancer: a meta-analysis.
AB  - BACKGROUND: Laparoscopic rectal cancer surgery aims to provide patients with
      curative resection while minimizing postoperative morbidity and mortality. This
      study used meta-analytical techniques to compare laparoscopic and open surgery as
      the primary treatment for patients with rectal cancer with regard to short-term
      and long-term outcomes. METHODS: A literature search was performed on all studies
      between 1993 and 2004 comparing laparoscopic and open surgery for rectal cancer.
      Subgroup analysis was performed on patients undergoing abdominoperineal excision
      of the rectum. The following end points were evaluated: operative outcomes,
      postoperative recovery, and early and late adverse events. RESULTS: Twenty
      studies matched the selection criteria and reported on 2071 subjects, of whom 909
      (44%) underwent laparoscopic and 1162 (56%) underwent open surgery for rectal
      cancer. Time to stomal function (weighted mean difference [WMD], -1.52; 95%
      confidence interval [95% CI], -2.20, -1.01), first bowel movement (WMD, -.72; 95%
      CI, -1.21, -.22), feeding solids (WMD, -.92; 95% CI, -1.35, -.50), and length of
      hospital stay (WMD, -2.67; 95% CI, -3.81, -1.54) were all significantly reduced
      after laparoscopic surgery. In patients who underwent abdominoperineal excision
      of the rectum, wound infection (odds ratio, .15; 95% CI, .03, .73) and
      requirement for postoperative parenteral analgesia (WMD, -.63; 95% CI, -1.22, 
      .04) were also significantly reduced. There was no difference between groups in
      the extent of oncological clearance. CONCLUSIONS: Laparoscopic rectal cancer
      surgery results in an earlier postoperative recovery and a resected specimen that
      is oncologically comparable to open surgery. Results from randomized trials
      reporting long-term outcomes such as cancer recurrence (local and metastatic) and
      5-year survival are eagerly awaited.

PMID- 16450221
TI  - Can rectal cancers with pathologic T0 after neoadjuvant chemoradiation (ypT0) be
      treated by transanal excision alone?
AB  - BACKGROUND: Patients with rectal cancer who have complete rectal wall tumor
      regression after neoadjuvant chemoradiation probably have eradication of tumor
      cells in the mesorectum as well, thus raising the possibility of transanal
      excision. METHODS: All pathology reports of all patients with locally advanced
      low and mid rectal cancer who underwent preoperative chemoradiation followed by
      radical resection from May 2000 to June 2004 were reviewed to evaluate the
      correlation between complete tumor response (ypT0) and nodal response. RESULTS:
      One hundred one consecutive patients had neoadjuvant chemoradiation followed by
      definitive operation. Four were excluded, leaving 64 men and 33 women (median
      age, 62 years). Fifty-three patients (55%) had mid rectal cancer, and 44 (45%)
      had low rectal cancer. Fifty-eight patients (60%) underwent low anterior
      resection, and 36 (37%) underwent abdominoperineal resection. In 17 patients
      (18%), no residual tumor cells were present within the rectal wall. One patient
      (6%) with ypT0 disease had positive lymph nodes. CONCLUSIONS: No residual tumor
      in the rectal wall correlates with the absence of viable cancer cells in the
      mesorectal tissue (94%). Approximately 10% of T1 tumors have involved lymph
      nodes, and local excision is an accepted option. Transanal excision could
      probably be considered in a highly selected group of patients with a mural
      pathologic complete response to neoadjuvant therapy. This approach should be
      prospectively investigated, and strict selection guidelines should be used.

PMID- 16450222
TI  - Assessment of dementia in an HIV-positive population in an ambulatory clinic.

PMID- 16450223
TI  - Neo-Pagan patients' preferences regarding physician discussion of spirituality.

PMID- 16450224
TI  - Unexpected mailed survey response rates.

PMID- 16450225
TI  - Education for all in clinical prevention and population health: an opportunity
      for family medicine educators.

PMID- 16450226
TI  - Regaining balance after "reality vertigo:" teaching learners to attend to the
      psychological aspects of patients with chronic, nonmalignant pain.

PMID- 16450229
TI  - Using movie clips to foster learners' reflection: improving education in the
      affective domain.

PMID- 16450227
TI  - Incorporating caries prevention into the well-child visit in a family medicine
      residency.
AB  - BACKGROUND: The Centers for Disease Control and Prevention reports that topical
      fluoride application may prevent early childhood caries in high-risk populations.
      Yet, there are few published descriptions of caries prevention curricula for
      primary care residents. METHODS: In 2003, the New Hampshire-Dartmouth Family
      Practice Residency hired a dentist and a hygienist to develop and implement a
      didactic and practical oral health curriculum. RESULTS: Over 2 years, faculty and
      residents competent with oral health screening and fluoride varnish application
      rose from 0% to 69% to 100%. In the same period, the percentage of well-child
      visits (ages 6 months to 3 years) with documented oral health screening and
      fluoride varnish application rose from 0% to 80% to 91%. CONCLUSIONS: Our
      successful model of teaching early childhood caries prevention services within
      the well-child visit could be replicated by other residency programs. Programs
      may need start-up funding for initial training by dental professionals.

PMID- 16450230
TI  - Bridging the gap: a curriculum to teach residents cultural humility.
AB  - BACKGROUND AND OBJECTIVES: Family physicians are expected to provide culturally
      sensitive care. However, teaching about cultural diversity and measuring
      educational outcomes can be challenging. We describe a diversity curriculum based
      on the concept of cultural humility, which includes participatory didactic and
      structured learning activities. METHODS: Two classes of second-year family
      medicine residents participated in a yearlong diversity curriculum. Self
      assessment and observational data were collected before and after the curriculum.
      RESULTS: Observational data showed that residents increased patient involvement
      during office visits. Ratings by announced and unannounced simulated patients
      indicated that residents were attentive to the patient's perspective and social
      context. Resident ratings indicated high satisfaction with the learning
      activities. Self-assessment data did not show significant changes in residents'
      perception of their ability to work with particular patients. CONCLUSIONS:
      Participatory learning activities that focus on cultural humility are a promising
      approach for diversity education.

PMID- 16450231
TI  - Cesarean delivery results in a family medicine residency using a specific
      training model.
AB  - BACKGROUND AND OBJECTIVES: This study describes and evaluates a teaching model
      for training family medicine residents to perform cesarean deliveries and
      determines whether family medicine residents can achieve adequate quality care in
      the procedure. METHODS: The teaching model for cesarean deliveries involved
      direct instruction and supervision by an obstetrician. We conducted a review of
      all cesarean deliveries performed over a 3-year period by family medicine
      residents. The review analyzed associated medical conditions, cesarean section
      indications, cesarean rate, blood loss, postoperative complications, and fetal
      outcome. We compared these data to published outcomes in obstetrical literature
      and local obstetricians' data. RESULTS: Maternal outcomes of all 277 cases
      performed under the teaching model were similar to other published results. The
      family medicine residency's cesarean section rate (19.1%) was less than the
      national cesarean section rate (27.6%) and the local obstetricians' rate (22.6%).
      CONCLUSIONS: The teaching model outlined provides family medicine residents with
      the knowledge and skill to perform cesarean deliveries with high-quality
      standards.

PMID- 16450232
TI  - Practice patterns in sildenafil prescribing.
AB  - BACKGROUND: This study explores the incorporation of sildenafil into treatment of
      the common conditions of psychosexual and erectile dysfunction (ED). METHODS: The
      2002 National Ambulatory Medical Care Survey and the National Hospital Ambulatory
      Medical Care Survey were analyzed for visits in which sildenafil was prescribed.
      Patient, visit, and provider characteristics for visits in which sildenafil was
      prescribed were compared between visits that documented a presenting complaint or
      diagnosis consistent with ED and those without documentation consistent with ED.
      RESULTS: Of visits by men 30 years or older receiving sildenafil, 50% had no
      documented presenting complaint or diagnosis consistent with ED. No significant
      differences were found between those prescribed sildenafil with or without a
      reason for visit or diagnosis of ED based on age, race, or payment type.
      Individuals with more visits in the last 12 months were significantly less likely
      to have a recorded diagnosis consistent with ED. Urologists documented ED
      significantly more often than family medicine, internal medicine, and other
      physicians. CONCLUSIONS: Sildenafil is being prescribed at a significant number
      of visits without documentation of a reason for visit or diagnosis consistent
      with psychosexual or erectile dysfunction.

PMID- 16450233
TI  - Protecting participants in family medicine research: a consensus statement on
      improving research integrity and participants' safety in educational research,
      community-based participatory research, and practice network research.
AB  - Recent events that include the deaths of research subjects and the falsification
      of data have drawn greater scrutiny on assuring research data integrity and
      protecting participants. Several organizations have created guidelines to help
      guide researchers working in the area of clinical trials and ensure that their
      research is safe and valid. However, family medicine researchers often engage in
      research that differs from a typical clinical trial. Investigators working in the
      areas of educational research, community-based participatory research, and
      practice-based network research would benefit from similar recommendations to
      guide their own research. With funding from the US Office of Research Integrity
      and the Association of American Medical Colleges, we convened a panel to review
      issues of data integrity and participant protection in educational research,
      community-based participatory research, and research conducted by practice-based
      networks. The panel generated 11 recommendations for researchers working in these
      areas. Three key recommendations include the need for (1) all educational
      research to undergo review and approval by an institutional review board (IRB),
      (2) community-based participatory research to be approved not just by an IRB but
      also by appropriate community representatives, and (3) practice-based researchers
      to undertake only valid and meaningful studies that can be reviewed by a central
      IRB, rather than separate IRBs for each participating practice.

PMID- 16450234
TI  - Exploring the mission of primary care.
AB  - OBJECTIVE: This paper's objective was to examine the mission statements of the
      sponsoring boards and professional organizations of the primary care specialties.
      METHODS: Mission statements were obtained from the Web sites of the specialty
      boards and academies for each of the four primary care specialties of pediatrics,
      obstetrics-gynecology, general internal medicine, and family medicine. The
      mission statements were analyzed by two investigators, and the components of each
      mission statement were identified and categorized. RESULTS: There were 29
      distinct characteristics defined among all the mission statements. Three of the
      four primary care specialty organizations listed 10 components, while the
      American Academy of Pediatrics contained the fewest, with three components. The
      most commonly named characteristics were commitment to public health and
      education along with assuring high-quality standards. There was little overlap
      among the mission statements. Several qualities listed by the Institute of
      Medicine were not included in the mission statements and three-patient trust,
      integration of services, and personalized treatment-were missing from all
      sources. CONCLUSIONS: The mission statements of the primary care specialties vary
      widely in their values and goals. The findings here provide a perspective that
      may help focus collaboration and contribute to the discussion surrounding primary
      care.

PMID- 16450237
TI  - The talking cure.

PMID- 16450236
TI  - Fish, isms, medicine, and marriage.

PMID- 16450235
TI  - An interactive web-based curriculum on evidence-based medicine: design and
      effectiveness.
AB  - BACKGROUND AND OBJECTIVES: Medical education experts have called for improved
      training in evidence-based medicine (EBM) and the increased use of e-learning
      technologies in medical education. In response, we developed an interactive, Web
      based curriculum on key aspects of EBM in family medicine. METHODS: Students
      participating in a 6-week family medicine clerkship (n=238) were randomly
      assigned to intervention (n=134) or control (n=104) groups. Both groups
      participated in the traditional clerkship experience, but intervention group
      students received additional training via an on-line curriculum that included
      learning modules in MEDLINE searching skills, EBM skills, and the calculation of
      the number needed to treat (NNT) statistic. The on-line curriculum was evaluated
      using a case-control design with a test case at the clerkship's end. RESULTS:
      Results suggested that the on-line curriculum was effective, with experimental
      group students outperforming control group participants on a variety of measures,
      including the number of MEDLINE searches conducted during the clerkship (13
      searches versus 3 searches) and the quality of literature search strategies on an
      evaluation patient case study (2.9 versus 2.1 on a 1=poor to 4=excellent scale).
      Intervention group students reported greater confidence and enjoyment in
      searching the biomedical journal literature via MEDLINE and were more likely to
      identify the best articles (randomized controlled trials or meta-analyses) for
      the evaluation case from among those retrieved (60% versus 34%). In addition,
      intervention group students' abilities to correctly calculate the NNT were
      significantly higher than those of control group participants (73% versus 27%).
      Intervention group students were more likely than control subjects to report
      learning from other students during the clerkship. CONCLUSIONS: This study
      demonstrates that an e-learning approach to educating medical students to
      effectively search MEDLINE for articles meeting the criteria for evidence-based
      practice can result in higher-quality literature search strategies,
      identification of higher-quality evidence, and improved confidence in information
      retrieval and analysis skills.

PMID- 16450238
TI  - United Kingdom: Sicker patients are referred more often.

PMID- 16450239
TI  - Republic of Marshall Islands: US residents and an international rotation.

PMID- 16450241
TI  - Canada: What can be done to get more students from rural areas to go to medical
      school?

PMID- 16450240
TI  - Finland: A method of creating and distributing evidence-based guidelines.

PMID- 16450252
TI  - [New ARMD severity scale. What is it used for?].

PMID- 16450253
TI  - Antisense oligonucleotides, aptamers and SiRNA: promises for the treatment of
      ocular diseases.

PMID- 16450254
TI  - [Capsular bag distention syndrome].

PMID- 16450255
TI  - [Age-related macular degeneration: its association with the epsilon4 allele of
      the apolipoprotein E gene].
AB  - OBJECTIVE: The apolipoprotein E (APOE) epsilon4 allele is a well-established
      factor associated with age-related macular degeneration (AMD). This disorder is
      characterized by a typical progressive central visual impairment. Our aim was to
      study further the relationship of the APOE genotype associated with AMD.
      MATERIALS AND METHODS: We evaluated a group of 95 patients with AMD and 65
      controls. The APOE genotype for each participant in the study was determined.
      RESULTS: The allele was associated with age-related macular degeneration (OR =
      5.6; 95% CI = 3.4-8.8 ; p < 0.001). Female patients with at least one epsilon4
      allele had a significantly earlier age at diagnosis (epsilon4+ = 72.2 S.D. 5.1;
      epsilon4- = 78.8 +/- 5.7; p < 0.001). CONCLUSIONS: The APOE epsilon4 allele is
      not a protective factor for AMD, but is associated with an increased risk of its
      development.

PMID- 16450257
TI  - [Study of the retinal nerve fiber layer in childhood strabismus].
AB  - OBJECTIVE: To assess possible differences in the retinal nerve fiber layer (RNFL)
      thickness between children with strabismus and controls. This study also compared
      esotropia with exotropia cases, and dominant eyes with non-dominant eyes. METHOD:
      31 children with esotropia, 17 children with exotropia and 32 controls were
      studied. The peripapillary RNFL average thickness was determined in 4 different
      areas (inferior, superior, nasal and temporal) using optical coherence
      tomography. Statistical analysis was performed a) between the strabic children
      and the control group, b) between the esotropia and exotropia groups, and c)
      between the dominant eyes and the non-dominant eyes of the strabic children.
      RESULTS: No statistically significant differences in RNFL thickness were found in
      any of these statistical comparisons. CONCLUSIONS: From this study, no evidence
      of changes in RNFL thickness, associated to the existence of strabismus, were
      found.

PMID- 16450256
TI  - [Cholesterol, alpha-tocopherol, and retinoid concentrations in silicone oil used
      as a vitreous substitute].
AB  - OBJECTIVE: To verify the existence of organic lipophylic compounds in silicone
      oil extracted from human eyes following its use for previous retinal detachment,
      and to determine the intraocular permanence time of these substances in the oil.
      METHODS: Concentrations of retinoic acid, retinol, retinal, cholesterol and alpha
      tocopherol were detected by HPLC in 23 samples of silicone oil extracted from
      patients with complicated retinal detachments. The time interval between the time
      of injection of the silicone oil and the subsequent assessment varied from 3 to
      50 months (the permanence time). RESULTS: All tested compounds were found in the
      samples, but these were most commonly cholesterol and less frequently alpha
      tocopherol. There was an inverse relationship between retinoic acid concentration
      and age (p=0.023), and a direct relationship between cholesterol concentration
      and permanence time (p=0.0008) at least up to 20 months. CONCLUSIONS: These
      findings confirm that silicone oil is not an inert substance but is capable of
      extracting lipophylic compounds from the intraocular tissues. There is a clear
      linear elevation of cholesterol levels with increased intraocular permanence
      time. This finding could be used to further establish a safe permanence time for
      intraocular silicone oil used in ophthalmologic surgery. More studies with larger
      samples are warranted to evaluate this further.

PMID- 16450258
TI  - [Oxidative stress in a model of experimental diabetic retinopathy: the utility of
      peroxinytrite scavengers].
AB  - PURPOSE: The retina is the neurosensorial tissue of the eye and is extremely rich
      in polyunsaturated lipid membranes. This feature makes it especially sensitive to
      oxygen and/or nitrogen activated species and lipid peroxidation. Several authors
      have postulated the importance of superoxide (O2-) and peroxynitrite production
      in the development of diabetic complications. In the present study, we have used
      two different antioxidants, ebselen and lutein, that present as a common feature
      their peroxynitrite scavenging capacity, to ameliorate the oxidative stress that
      exists in the retina in diabetic patients. METHODS: Hyperglycemia was
      accomplished by the intraperitoneal injection of Alloxan in a mouse model of
      diabetic retinopathy. Malondialdehyde (MDA) and glutathione (GSH) concentrations
      in eye homogenates (without the lens) were determined. We also recorded serial
      electroretinograms (ERG) and measured latency and implicit times. RESULTS: The
      MDA concentration increased and the GSH concentration decreased in the eyes of
      the diabetic animals. Treatment with ebselen and lutein restored the MDA and GSH
      concentrations to control values. Latency and implicit times were not affected by
      the diabetes. CONCLUSION: New studies are required to better understand the
      protective mechanism of ebselen and lutein in this model of experimental diabetic
      retinopathy.

PMID- 16450259
TI  - [Optic nerve glioma in a case of neurofibromatosis-1 in a child].
AB  - CLINICAL CASE: The case of a three-year-old patient with neurofibromatosis type I
      is presented. Ophthalmologic evaluation revealed, by means of magnetic resonance
      imaging, the presence of a silent glioma in the optic nerve of the left eye.
      DISCUSSION: Neurofibromatosis-1 can present in multiple ways to the
      ophthalmologist, with a glioma of the optic nerve being one of the most frequent
      central nervous system presentations in this illness. Generally the glioma
      affects the optic chiasm and its course is indolent, with conservative management
      and close monitoring usually being advised until progression is defined.

PMID- 16450260
TI  - [Tuberculous papillitis].
AB  - CASE REPORT: We describe a 65-year-old asymptomatic woman with unilateral optic
      disc edema. Laboratory testing revealed a very marked positive PPD (25 mm) with
      dermatolysis. Anti-tuberculosis therapy resulted in complete resolution.
      DISCUSSION: Tuberculosis should be considered in the diagnosis of papillitis,
      even in asymptomatic patients.

PMID- 16450262
TI  - [Contralateral amaurosis and extraocular muscle palsies after retrobulbar
      injection].
AB  - CASE REPORT: We report a rare complication of retrobulbar anesthesia in
      ophthalmic surgery-amarurosis and extraocular muscle palsies in the contralateral
      eye. Our patient did not suffer permanent sequelae from the injection.
      DISCUSSION: Numerous complications resulting from retrobulbar injections in the
      eye and orbit have been reported. One possible explanation of this case is the
      inadvertent penetration of the subdural or subarachnoid space surrounding the
      optic nerve and the injection of anesthetic into that space. The drug then tracks
      along the ipsilateral optic nerve to the chiasm and then to the contralateral
      optic nerve. Several methods of decreasing the probability of such a complication
      are discussed.

PMID- 16450261
TI  - [Bilateral sixth nerve and left third nerve palsy after head trauma].
AB  - CASE REPORT: To describe a case of combined bilateral cranial nerve palsy of
      traumatic origin. To determine the lesions that produce the symptoms is useful to
      define the final prognosis and the best treatment. DISCUSSION: We report the case
      of a patient who developed a bilateral sixth nerve and left third nerve palsy
      after head trauma. The underlying lesion was a diffuse axonal injury. After an
      observation period during which no spontaneous improvement occurred, we
      administered botulinum toxin with a successful clinical result. Bilateral
      combined traumatic cranial nerve palsies are rare. When a diffuse axonal injury
      is present, the chance of spontaneous resolution is poor.

PMID- 16450263
TI  - [The XIII hispanic american ophthalmology society meeting (1923) and "the use of
      eyeglasses" (1623)].

PMID- 16450264
TI  - [The convex mirrors in flamenco paintings (II)].

PMID- 16450266
TI  - From concept to practice: the recent history of preterm delivery prevention. Part
      I: cervical competence.
AB  - The prevention of preterm delivery (PTD) is a major desiderate in contemporary
      obstetrics and a societal necessity. The means to achieve this goal remain
      elusive, and the research efforts have been punctuated by several ineffective
      intervention proposals. More recently, new areas of proposed preventive strategy
      have arisen, focusing on cervical competence, subclinical infection, and hormonal
      effects. This review, based on a comprehensive and unbiased review of the
      available literature, will address the rationale and current status of these new
      concepts of significant clinical interest. We will describe the microcosm of
      thought and research dedicated to the prevention of PTD during the last 10 years,
      and the arduous efforts to establish a linkage between predictive observations
      and therapeutic hypotheses. In its first part, the review will discuss the
      recently emerging view that regardless of the preterm labor etiology, a common
      pathway is eventually reached, reflected in cervical changes. The new concept of
      functional cervical insufficiency is addressed from the perspective of cervical
      assessment by ultrasound. Although the existing research has not accurately
      quantified yet the usefulness of ultrasound cervical examination, the technique
      has become commonplace. Several recent studies have demonstrated a continuum of
      risk between shorter cervix on ultrasound and higher rate of PTD, leading to the
      hypothetical argument that women with short cervix on ultrasound might benefit
      from cervical cerclage. Observational and randomized clinical trials of cerclage
      as a modality of pregnancy prolongation have provided conflicting results. The
      relative paucity of data and the conflicting nature of the available evidence
      dictate caution whenever decisions for cervical monitoring or intervention are
      made.

PMID- 16450268
TI  - The effect of maternal diet restriction on pregnancy outcome.
AB  - The purpose of this study was to determine the effect of intermittent maternal
      fasting on pregnancy outcome. The course and outcome of 168 fasted pregnant women
      were reviewed. A total of 168 fasted and 156 control pregnant women were studied.
      The incidence of gestational diabetes (GDM) was significantly higher in the
      fasted group than in the control group ( p = 0.001). Labor was induced in 26 of
      168 women (15.5%) in the fasted group compared with 11 of 156 women (7.1%) in the
      control group ( p = 0.004). The cesarean section rate was significantly higher in
      the fasted group ( p = 0.01). There was no difference in Apgar score at 1 and 5
      minutes between the two groups. Admission to the special care baby unit (SCBU)
      was significantly more frequent in the fasted group than the control group ( p =
      0.001). Maternal diet restriction is associated with an increased risk of GDM and
      induction of labor. The frequency of neonatal admission to SCBU is increased.

PMID- 16450267
TI  - Postterm pregnancy: practice patterns of contemporary obstetricians and
      gynecologists.
AB  - The purpose of this study was to determine the management of postterm pregnancy
      by contemporary practicing obstetricians. A questionnaire investigating practice
      patterns pertaining to postterm pregnancy was mailed to 1000 randomly selected
      American College of Obstetricians and Gynecologists (ACOG) Fellows and Junior
      Fellows in March 2004. The response rate was 52.2% (522/1000). Statistical
      analysis included the answers from the 420 practicing obstetricians. Males
      comprised 55.7% (234/420) of the responding obstetricians. The majority of
      responding obstetricians (95.4%) rated their residency training regarding
      management of postterm pregnancy as adequate or comprehensive. Forty-eight
      percent define postterm pregnancy as 42 weeks gestation or greater, whereas 43.1%
      consider 41 weeks gestation or greater to be postterm. Seventy-three percent
      routinely induce low-risk patients with singletons at 41 weeks gestation. If
      patients decline induction at 41 weeks or if the practitioner does not induce
      patients until after 41 weeks gestation, the majority of respondents (64.8% and
      65.0%, respectively) start postterm pregnancy fetal testing in singletons at 41
      weeks and obtain testing twice weekly. Most (64.6%) use cervical ripening agents
      when inducing both nulliparous and multiparous patients with unfavorable
      cervices. The majority of practitioners (97.3%) do not use prostaglandins when
      inducing postterm patients with one previous cesarean delivery. Although most
      respondents manage postterm pregnancy according to recent ACOG educational
      materials with regard to antenatal fetal surveillance and methods of induction,
      the majority induce patients with singleton postterm pregnancies at 41 weeks
      gestation rather than at 42 weeks gestation.

PMID- 16450269
TI  - Pregnancy outcome following second-trimester amniocentesis: a case-control study.
AB  - The purpose of this study was to investigate whether second-trimester
      amniocentesis increases fetal loss rate. Two thousand sixty-eight women with
      singleton gestations who underwent mid-trimester amniocentesis at 15 to 22 weeks
      gestation and 2068 controls matched one-to-one for maternal age, parity, and the
      number of prior spontaneous abortions were studied prospectively in a case
      control study design. The fetal loss rates and other adverse pregnancy outcomes
      were compared between the study and control groups using the Pearson chi2 test or
      Fisher exact test when appropriate. In the amniocentesis group, eight (0.4%)
      fetal losses occurred within 30 days of the procedure, and in the control group,
      six (0.3%) losses occurred within 30 days of the inclusion in the study; the
      difference was not statistically significant ( p = 0.59; OR, 1.34; 95% CI, 0.46
      to 3.85). The total fetal loss rates including spontaneous abortions and
      intrauterine fetal deaths/stillbirths were 2.3 and 2% in the study and control
      groups, respectively, and the difference was not significant ( p = 0.59; OR,
      1.12; 95% CI, 0.74 to 1.71). Amniotic fluid leakage occurred in only two (0.1%)
      of 2068 study patients. Transplacental needle passage was not associated with an
      increased risk of pregnancy loss compared with nontransplacental amniocentesis (
      p = 0.92; OR, 0.96; 95% CI, 0.47 to 1.95). There was no statistically significant
      difference in fetal loss rate between women requiring two needle insertions to
      obtain amniotic fluid and those having only one insertion ( p = 1.00; OR, 0.75;
      95% CI, 0.10 to 5.53). The rates of preterm deliveries, small for gestational age
      infants, preeclampsia/eclampsia, placental abruptions, and cesarean deliveries
      were also not significantly different between two groups (each p > 0.05). We
      conclude that second-trimester amniocentesis for prenatal diagnosis is a safe
      procedure that does not appear to increase fetal loss rate.

PMID- 16450270
TI  - Plasma homocysteine in late pregnancies complicated with preeclampsia and in
      newborns.
AB  - The aim of this study was to determine the relationship between maternal serum
      homocysteine levels in preeclampsia and the severity of the disease, neonatal
      serum homocysteine levels, maternal complications, and fetal outcome. Fifty
      pregnant women were included in this prospective study, of which 25 were severe
      (group I) and 25 were non-severe preeclamptic (group II). Maternal and neonatal
      serum homocysteine levels were measured by the fluorescence polarization
      immunoassay (FPIA) method. Maternal homocysteine levels in both groups were
      compared. The association of maternal and neonatal serum homocysteine levels with
      maternal complications and fetal outcome was investigated. When the maternal
      serum homocysteine cut-off value was accepted as 15 micromol/L, significant
      differences in relation to maternal (eclampsia; hemolysis, elevated liver
      enzymes, and low platelet count syndrome) and fetal (in utero mort fetalis, low
      birthweight) complications were observed between the group with maternal serum
      homocysteine level > 15 micromol/L and the group with maternal serum homocysteine
      level < or = 15 micromol/L ( p < 0.05). Hyperhomocysteinemia during pregnancy is
      a risk factor for both development of preeclampsia and its complications. Given
      that the diagnosis and treatment of hyperhomocysteinemia is possible, clinical
      trials to determine whether treatment to reduce homocysteine would be valuable in
      the prevention of both maternal and fetal complications in preeclampsia should be
      designed.

PMID- 16450271
TI  - Peripherally inserted central venous catheters in newborn infants: malpositioning
      and spontaneous correction of catheter tips.
AB  - Peripherally inserted central venous catheters (PICCs) are increasingly used in
      the neonatal intensive care unit (NICU). Malpositioning of the catheter's tip is
      a known occurrence that may require repositioning or removal of the catheter. We
      report our experience with insertion and management of PICCs at the NICU of King
      Fahad National Guard Hospital in Riyadh, Saudi Arabia, over a 1-year period. We
      also report on five newborn infants in whom the tips of the catheters were
      malpositioned. Their subsequent course showed spontaneous correction of the tips
      of those catheters within 1 day.

PMID- 16450272
TI  - Neonatal subgaleal hematoma: presentation and outcome--radiological findings and
      factors associated with mortality.
AB  - To describe the presentation and outcome of infants who develop subgaleal
      hematoma (SGH), we compared perinatal factors, clinical and head imaging
      findings, and outcome in a cohort (N = 34) of all infants admitted to Saint Louis
      Children's Hospital neonatal intensive care unit with SGH from January 1991 to
      June 2003. All except three of the infants admitted with SGH had instrumental
      deliveries (31 of 34; 91.2%): 21 vacuum, eight vacuum followed by forceps, two
      forceps). There was also a high frequency of occurrence of associated
      intracranial hemorrhage (17 of 34; 50%: subarachnoid hemorrhage, n = 4;
      intraventricular hemorrhage, n = 4; intraparenchymal hemorrhage, n = 4; subdural
      hemorrhage, n = 11), and skull fracture (six of 34; 19.4%; three of six [50%] of
      them depressed fractures). There was mortality associated with SGH (four of 34,
      11.8%); those who died had significant volume loss with anemia, coagulopathy, and
      shock requiring large volumes of blood and blood products transfusions. The
      presence of ICH did not correlate with the severity of SGH or mortality, but the
      severity of SGH correlates with mortality. Minor neurological abnormalities were
      noted in only four infants at discharge. In conclusion, SGH is an uncommon type
      of birth trauma, and is associated with delivery or attempted delivery by
      instrumentation (vacuum and/or forceps). Severe hypovolemia and coagulopathy, but
      not intracranial hemorrhage, were the most commonly associated clinical problems
      with mortality. ICH does not correlate with severity of SGH. A brain computed
      tomography or magnetic resonance imaging should be considered in evaluating a
      clinically symptomatic SGH. There is associated mortality in severe cases but
      short-term outcome in survivors is good.

PMID- 16450273
TI  - Fetomaternal hemorrhage caused by intraplacental choriocarcinoma: a case report
      and review of literature in Japan.
AB  - Fetomaternal hemorrhage induced by intraplacental choriocarcinoma is considered
      to be extremely rare. We herein describe a neonate with severe anemia caused by
      intraplacental choriocarcinoma that was histopathologically identified after
      birth. Furthermore, we reviewed three other such cases in Japan. As a result, the
      incidence of intraplacental choriocarcinoma may be higher than previously
      estimated. Therefore, we suggest that the placenta should be examined in any
      suspected cases of fetomaternal hemorrhage.

PMID- 16450274
TI  - Fetal pericardial teratoma: presentation of two cases and review of literature.
AB  - We present the fetal ultrasound and echocardiographic findings and clinical
      outcome of two fetuses with intrapericardial teratoma encountered in our
      institution. In the first (diagnosed at 19 weeks of gestation) case there was
      elective termination of pregnancy; in the second case (diagnosed at 24 weeks), a
      pericardio-amniotic shunt was placed after reaccumulation of fluid following
      pericardiocentesis. We review the published experience of intrapericardial
      teratomas, focusing on the diagnosis, fetal echocardiographic findings, and
      outcome with and without prenatal intervention.

PMID- 16450275
TI  - Fatal illness associated with pulmonary hypertension in a neonate caused by
      intrauterine echovirus 11 infection.
AB  - Nonpolio enterovirus (NPEV) infections are known to cause a wide range of
      illnesses in the neonatal period. In most cases, NPEV is presumed to be
      contracted during birth. Intrauterine NPEV infections occur infrequently. A case
      of intrauterine echovirus 11 infection with pneumonia, persistent pulmonary
      hypertension of the newborn, and purpura fulminans is presented.

PMID- 16450276
TI  - Nonimmune hydrops fetalis due to generalized lymphatic dysplasia in an infant
      with Robertsonian trisomy 21.
AB  - We report the first case of generalized lymphatic dysplasia and trisomy 21
      presenting with nonimmune hydrops fetalis. This infant showed intractable
      chylothorax, chylous ascites, and periodic bouts of edema. A karyotype analysis
      revealed Robertsonian trisomy 21: 46,XY,t(14q21q)(q10;q10) +21. This patient died
      of multiple organ failure at 400 days of life, despite the management of chylous
      effusions. The lymphoscintigraphy and histopathological findings led to the final
      diagnosis of generalized lymphatic dysplasia, which might also contribute to the
      development of hydrops. Refractory chylothorax in trisomy 21 patients may
      emphasize the need for intensive scrutiny of lymphatic disorders.

PMID- 16450277
TI  - Three-dimensional first-trimester transvaginal diagnosis of alobar
      holoprosencephaly associated with omphalocele in a 46,XX fetus.
AB  - A three-dimensional (3D) transvaginal diagnosis of alobar holoprosencephaly (HPE)
      with associated omphalocele is reported at 12 weeks, 3 days gestation. Diagnosis
      of HPE was based on visualization of a single holoprosencephalic cavity with
      absent falx and basal ganglia and omphalocele by the presence of abdominal wall
      defect with mid-gut herniation. Chorionic villus sampling showed a normal 46,XX
      karyotype. 3D volumetric reconstruction allowed a more detailed definition of the
      anatomic landmarks of the lesion, including visualization of a thin rim of
      cortical mantel within the prosencephalic cavity, the dysmorphic face with
      flattened nose, and the abdominal eventration that looked like an abdominal air
      bag on 3D volumetric reconstruction.

PMID- 16450278
TI  - Sporadic Larsen syndrome in a preterm female originally diagnosed as positional
      deformities due to oligohydramnios.
AB  - Few reports describe incidental prenatal diagnosis of sporadic Larsen syndrome by
      ultrasound, but none of these discuss coincidental oligohydramnios or an
      association with fetal growth restriction. A 28-year-old woman had prolonged
      rupture of membranes causing marked oligohydramnios at 32 weeks gestation in her
      first pregnancy. Labor was induced by vaginal prostaglandins and oxytocin
      infusion after dexamethasone administration because of concern about placental
      abruption. She delivered vaginally a live female infant weighing 1960 g (< 10th
      percentile) with multiple skeletal malformations and characteristic facies
      originally suspected as positional. Newborn x-rays, however, established the
      diagnosis of Larsen syndrome with bilateral dislocations of the hips, knees (genu
      recurvatum), and ankles (club foot). The neonatal karyotype was 46,XX. Parental
      examination and family history were unremarkable. The newborn did well with
      bilateral lower extremities cast. Postnatal diagnosis of Larsen syndrome should
      be suspected in neonates with multiple skeletal abnormalities following
      oligohydramnios.

PMID- 16450279
TI  - [Qualification and education in gynecological oncology].
AB  - The German Medical Association (Bundesarztekammer) has launched a new
      organisational structure in the curriculum of medical qualification. Beside the
      field of obstetrics and gynecology this has led to three specialisation. The
      newly established specialisation is that of gynecological oncology. Therewith in
      the future the treatment and care for women with genital or breast cancer will be
      focused to those centers having the necessary qualification. In addition the
      German qualification is identical to that of the European Society of
      Gynecological Oncology (ESGO). So German fellows can obtain a national and
      international qualification at qualified centers.

PMID- 16450280
TI  - [Strategic aspects of DRGs in obstetrics and gynecology].

PMID- 16450281
TI  - [Diagnosis and treatment of malignant ovarian tumors 2005: recommendations of the
      Kommission Ovar of the AGO].
AB  - Recommendations for diagnosis and treatment of malignant ovarian tumors with
      regard to the most recent data were worked out in a consensus process and valued
      by level of evidence (LoE) and grade of recommendation (GoR) of the Canadian Task
      Force for Preventive Health Care by the members of the Kommission Ovar der
      Arbeitsgemeinschaft fur Gynakologische Onkologie (AGO) in June 2005. A short
      version of these guidelines is presented.

PMID- 16450282
TI  - [Endometrial cancer -- suggestions for the update of the guidelines].
AB  - Surgical therapy is the mainstay of the treatment of endometrial cancer. Apart
      from total abdominal hysterectomy und bilateral salpingo-oophorectomy, complete
      pelvic and paraaortic lymphadenectomy has become an integral part of the primary
      surgical procedure, allowing for definite surgical/histopathological staging. In
      surgically staged patients, adjuvant measures including external radiotherapy can
      be applied with a clear indication and unnecessary toxicity can be avoided. In
      addition complete lymphadenectomy has probably a relevant therapeutic effect. As
      so far no randomized trials have been completed and lymphadenectomy in the often
      multi-morbid and obese endometrial cancer patients requires a certain amount of
      expertise, it is not accepted by all experts or is accepted only if a variety of
      parameters obtained pre- and intraoperatively are present. On the other hand, the
      National Comprehensive Cancer Network of the USA recommends a complete pelvic and
      paraaortic lymphadenectomy for all patients with endometrial cancer, except for
      those with Stage IA, Grade 1 disease where this procedure is optional. The
      efficacy of an adjuvant pelvic teletherapy in Stage I patients has been
      questioned by several randomized trials. In patients having a complete surgical
      staging, external radiotherapy is often not necessary and can be replaced by
      vaginal brachytherapy. In advanced stages of endometrial cancer chemotherapy has
      been shown to be superior to whole abdominal radiotherapy. New multimodal
      concepts including surgical staging, adjuvant chemo- and targeted radiotherapy
      have to be evaluated. In the palliative setting novel endocrine strategies are
      being assessed in addition to the well established progestagen therapy. The
      efficacy of the standard chemotherapy with adriamycin/cisplatin could be somewhat
      improved by adding paclitaxel, at the expense of a markedly increased toxicity.
      Women with the diagnosis of endometrial cancer should be treated in the context
      of certified clinical trials as it has become the standard for patients with
      breast or ovarian cancer.

PMID- 16450283
TI  - [Unanswered questions in the management of cervical cancer].
AB  - The Task Force Group "Uterus of the Association of Gynecologic Oncology" has
      recently published the interdisciplinary S2 guidelines on diagnostics and therapy
      of cervical cancer. In view of quality development strategies of the German
      Cancer Society and the German Society for Obstetrics and Gynecology, a
      practicable concept with clear algorithms for gynecologists has been presented.
      Nevertheless, both development of oncologic sciences and daily practice, lead to
      new questions which should be answered by prospective studies. In this respect,
      women with cervical cancer should be treated on the same level of quality as
      patients with breast cancer. As discussed both nationally and internationally,
      laparoscopic staging, the development of laparoscopic surgical techniques (i. e.,
      laparoscopic-assisted radical vaginal hysterectomy), the safety and efficacy of
      the sentinel concept, and TMMR, and finally, the indication for trachelectomy are
      main scientific questions. Also, innovative vaccination studies that might
      increase hope of a breakthrough even in cervical cancer prevention, the
      implementation of nerve-sparing surgical techniques, the radical parametrectomy
      or current strategies on exenteration are main focuses of clinical gynecologic
      oncology.

PMID- 16450284
TI  - [Present relation of obstetrics and gynecology between the USA and Germany].
AB  - After World War II there was a blooming association between German and American
      Obstetricians-Gynecologists. When young German scientists began Fellowships in
      the US, they found German Professors of all ranks teaching in the various medical
      schools. At present there is no connection between the Deutsche Gesellschaft fur
      Gynakologie und Geburtshilfe (DGGG) and the American College of Obstetricians and
      Gynecologists ACOG. There is however a close cooperation between ACOG and the
      Berufsverband der Frauenarzte (BVF) who invite their presidents on a yearly
      basis. An advanced formalization of the affilitiation between the two German
      Societies and ACOG is expected to benefit all Societies while not interfering
      with European connections.

PMID- 16450285
TI  - [Adjuvant therapy with trastuzumab (Herceptin) in primary breast cancer].
AB  - The results of four randomized international multicentric trials evaluating the
      therapeutic benefit of Herceptin in the adjuvant treatment of HER2-neu positive
      primary breast cancer have been reported. These reports showed that even after
      short term follow up one year of Herceptin resulted in improved disease free,
      metastases free and overall survival. Design and results of these four studies
      and the recommendations of national and international societies for the use of
      Herceptin in the adjuvant setting will be discussed.

PMID- 16450286
TI  - [Minimizing operative morbidity. Sentinel-lymphonodectomy in vulvar cancer -- quo
      vadis?].
AB  - Complete groin dissection is established in the operative standard procedure in
      treatment of vulvar carcinoma. For lateral localized carcinomas without node
      metastases only ipsilateral dissection is necessary. But in early tumor stages
      most of the patients are node negative and no oncologic benefit can be postulated
      although operative morbidity is high. Only for carcinomas with depth of
      infiltration less than 1 mm it is possible to avoid groin dissection. Studies
      demonstrate that clinical and apparative diagnostic procedures do not predict
      lymph node involvement accurately. Thus the concept of sentinel-lymphonodectomy
      has been evaluated in the last years in vulvar carcinoma. With > 95 % detection
      rate was very high and false negative cases have been reported only very rarely.
      Because results with the first patients in Germany showed similar results the AGO
      developed a concept for an observational study which will avoid complete groin
      dissection in sentinel node negative T1-T2N0 vulvar carcinoma. Before
      participation is possible e learning phase has to be completed. Exact control of
      the patients should look for reduction of operative morbidity with equivalent
      oncologic effectiveness.

PMID- 16450287
TI  - [Vaginal revision of irritation of the obturator nerve within colposuspension].
AB  - Irritation of the obturator-nerve within colposuspension is a possible
      complication because of topographic proximity between obturator-nerve and
      operating-field. The main symptoms are weakness of the adductor muscles, sensory
      disturbance of thigh till paralysis and pain in the operating- field early after
      surgery. Too lateral fixing of the sutures in the pectineal ligament above the
      obturator-channel can cause compression of the obturator-nerve. Precocious
      intervention is a precondition for complete remission of symptoms, retropubic
      revise of surgery is evident. The method outlined here describes vaginal access
      for re-surgery with lateral colpotomy and dissection of the proximal
      colposuspension s suture. In this way a recurrent laparotomy with additional
      trauma of the operating-field can be avoided. In the case described here, this
      method led to the patients complete remission.

PMID- 16450288
TI  - Astragaloside IV from Astragalus membranaceus shows cardioprotection during
      myocardial ischemia in vivo and in vitro.
AB  - Astragaloside IV is the major active constituent of Astragalus membranaceus,
      which has been widely used for the treatment of cardiovascular diseases in China.
      However, the effects of astragaloside IV on myocardial ischemia and its
      mechanisms of action remain largely unknown. In this study, we have examined the
      effects of astragaloside IV on myocardial infarction and coronary flow in vivo
      and in vitro. The possible roles of its antioxidative and nitric oxide-inducing
      properties were also explored. Astragaloside IV significantly reduced infarct
      size in dogs subjected to coronary ligation in vivo. Astragaloside IV also
      improved post-ischemic heart function and ameliorated reperfusion arrhythmias in
      rat hearts in vitro. The cardioprotection of astragaloside IV was accompanied by
      a significant increase in coronary flow both in vivo and in vitro. The nitric
      oxide synthase inhibitor, Nomega-nitro- L-arginine methyl ester partially
      abrogated astragaloside IV's protective effect on heart function. Myocardial
      antioxidative enzyme superoxide dismutase activity increased with astragaloside
      IV administration. These data suggest the potential roles of antioxidative and
      nitric oxide-inducing properties of astragaloside IV in its protection from
      myocardial ischemia.

PMID- 16450289
TI  - Mediation of beta-endorphin by ginsenoside Rh2 to lower plasma glucose in
      streptozotocin-induced diabetic rats.
AB  - We investigated the plasma glucose-lowering mechanism(s) of Rh2, a ginsenoside
      derived from Panax ginseng, in rats with streptozotocin-induced diabetes (STZ
      diabetic rats). After intravenous injection over 120 min into fasting STZ
      diabetic rats, Rh2 decreased plasma glucose in a dose-dependent manner. In
      parallel to the lowering of plasma glucose, an increase of plasma beta-endorphin
      like immunoreactivity was observed. In addition, naloxone and naloxonazine at
      doses sufficient to block opioid mu-receptors inhibited the plasma glucose
      lowering action of Rh2 in genetically wild-type, diabetic mice. In contrast, Rh2
      failed to lower plasma glucose in opioid mu-receptor knockout diabetic mice. An
      increase in gene expression at both the mRNA and protein levels of glucose
      transporter subtype 4 (GLUT 4) was observed in soleus muscle obtained from STZ
      diabetic rats treated with Rh2 three times daily for one day; this increase in
      expression was absent when opioid mu-receptors were blocked. In conclusion, our
      results suggest that ginsenoside Rh2 may lower plasma glucose in STZ-diabetic
      rats based on an increase in beta-endorphin secretion that activates opioid mu
      receptors thereby resulting in an increased expression of GLUT 4.

PMID- 16450290
TI  - A preadipocyte differentiation assay as a method for screening potential anti
      type II diabetes drugs from herbal extracts.
AB  - A cell-based method for screening drug candidates from herbal extracts that have
      possible anti-type II diabetic effects was established. The differentiation of
      preadipocytes into adipocytes was used as a sensitive primary indicator of a
      drug's potential effect on type II diabetes. We established a quantitative method
      by using a computer image analysis system for assessing the morphological
      alterations. The assay was validated by screening compounds extracted from
      Chinese herbs and the known drug rosiglitazone for their capability of modulating
      PPARgamma gene expression and glucose uptake by adipocytes. Two drug candidates
      having possible anti-type II diabetic effects were identified.

PMID- 16450291
TI  - Direct and indirect mechanism(s) of antitumour activity of propolis and its
      polyphenolic compounds.
AB  - The immunomodulatory actions of a water-soluble derivative of propolis (WSDP) and
      two components of propolis, caffeic acid (CA) and caffeic acid phenethyl ester
      (CAPE) were investigated. Oral administration (50 mg/kg) of WSDP, CA, and CAPE
      enhanced the weight and cellularity of the spleen (p<0.05, p<0.01) of treated
      mice. The response of spleen cells to polyclonal mitogens (PHA, Con A, PWM) was
      also increased in mice treated with WSDP as compared to control (p<0.01); in
      contrast, the response of spleen cells of mice treated with CA were significantly
      suppressed (p<0.001). The colony forming ability of HeLa cells plated on
      monolayers of macrophages was completely inhibited by peritoneal macrophages from
      mice receiving either WSDP, CAPE, or CA. Macrophages from treated mice also
      inhibited [3H]TdR incorporation into HeLa cells in vitro. Testing for the
      possible presence of NO in the supernatants of 24 hours cultured macrophages
      activated with either compound revealed that the toxicity of these cells to HeLa
      cells was in part due to the production of NO. Tumour growth was suppressed by
      WSDP and its polyphenolic compounds given orally to mice. Local presence of CA,
      and CAPE in the tissue, caused a significant delay of tumour formation. Based on
      these results, we postulate that the antitumour activity of the test compounds
      includes pronounced immunomodulatory activity mainly due to the augmentation of
      non-specific antitumour resistance in mice via macrophage activation and the
      production of soluble factors by those cells which may interfere with either
      cells of the immune system or directly by tumour cells.

PMID- 16450292
TI  - Pheophorbide a, a major antitumor component purified from Scutellaria barbata,
      induces apoptosis in human hepatocellular carcinoma cells.
AB  - Scutellaria barbata has long been used as a Chinese medicine for the treatment of
      liver diseases such as hepatitis and hepatocellular carcinoma. In the present
      study, a bioassay-guided method was used to isolate the most active components
      from Scutellaria barbata. The anti-proliferative effects on human hepatoma HepG2
      and Hep3B cells of each fraction at every stage of the purification were
      monitored. An active component, which is 97% pure by high performance liquid
      chromatographic analysis, was isolated. Based on nuclear magnetic resonance (NMR)
      and mass spectrophotometric (MS) analysis, this active component was identified
      to be pheophorbide a (C35H36N4O5). Mechanistic studies showed that pheophorbide a
      induced apoptosis in Hep3B cells, a viral-induced hepatoma cell line. However, it
      was found to be non-toxic in normal human liver cells WRL-68. DNA fragmentation,
      sub-G1 cell cycle arrest, as well as suppression of the anti-apoptotic protein
      Bcl-2, release of cytochrome c to the cytosol, and activation of pro-caspase 3
      and pro-caspase 9 were observed when Hep3B cells were treated with 40 microg/mL
      (i. e., 67.5 microM) pheophorbide a for 48 hours. In conclusion, this is the
      first report describing the isolation of pheophorbide a from Scutellaria barbata
      using a bioassay-guided isolation method. The anti-proliferative activity and
      possible mechanisms of action of pheophorbide a on hepatoma Hep3B cells are also
      discussed.

PMID- 16450293
TI  - Attenuation of visceral nociception by alpha- and beta-amyrin, a triterpenoid
      mixture isolated from the resin of Protium heptaphyllum, in mice.
AB  - In the search for novel natural compounds effective against visceral nociception,
      the triterpenoid mixture alpha- and beta-amyrin, isolated from Protium
      heptaphyllum resin, was assessed in two established mouse models of visceral
      nociception. Mice were pretreated orally with alpha- and beta-amyrin (3, 10, 30,
      and 100 mg/kg) or vehicle, and the pain-related behavioral responses to
      intraperitoneal cyclophosphamide or to intracolonic mustard oil were analyzed.
      The triterpenoid mixture showed a dose-related significant antinociception
      against the cyclophosphamide-induced bladder pain, and at 100 mg/kg, the
      nociceptive behavioral expression was almost completely suppressed. Intracolonic
      mustard oil-induced nociceptive behaviors were maximally inhibited by 10 mg/kg
      alpha- and beta-amyrin mixture in a naloxone-reversible manner. While
      pretreatment with ruthenium red (3 mg/kg, s. c.), a non-specific transient
      receptor potential cation channel V1 (TRPV1) antagonist, also caused significant
      inhibition, the alpha (2)-adrenoceptor antagonist, yohimbine (2 mg/kg, s. c.),
      showed no significant effect. The triterpene mixture (10 mg/kg, p. o.) neither
      altered significantly the pentobarbital sleeping time, nor impaired the
      ambulation or motor coordination in open-field and rotarod tests, respectively,
      indicating the absence of sedative or motor abnormalities that could account for
      its antinociception. These results indicate that the antinociceptive potential of
      alpha- and beta-amyrin possibly involves the opioid and vanilloid (TRPV1)
      receptor mechanisms and further suggests that it could be useful to treat
      visceral pain of intestinal and pelvic origins.

PMID- 16450294
TI  - New sesquiterpene dimers from Inula britannica inhibit NF-kappaB activation and
      NO and TNF-alpha production in LPS-stimulated RAW264.7 cells.
AB  - A bioassay-guided isolation of an ethyl acetate-soluble extract of the aerial
      parts of Inula britannica var. chinensis (Rupr.) Regel, using an in vitro NF
      kappaB reporter gene assay, led to the isolation of four new sesquiterpene dimers
      bearing a norbornene moiety, inulanolides A-D, and three known sesquiterpenes,
      1,6alpha-dihydroxyeriolanolide, 1-acetoxy-6alpha-hydroxyeriolanolide, and
      eupatolide. The structures of the new compounds were elucidated by spectroscopic
      methods. Among these compounds, inulanolides B and D and eupatolide, exhibited
      potent inhibitory activity on the LPS-induced NF-kappaB activation with IC50
      values of 0.49 microM, 0.48 microM, and 1.54 microM, respectively. Consistent
      with their inhibitory effect on NF-kappaB activation, compounds and also strongly
      inhibited the production of NO and TNF-alpha in the LPS-stimulated RAW264.7 cells
      with IC50 values in the range of 2 microM.

PMID- 16450295
TI  - Xanthine oxidase inhibitors from the flowers of Chrysanthemum sinense.
AB  - From the MeOH extract of the flowers of Chrysanthemum sinense, a new flavone
      glucoside, acacetin 7- O-(3- O-acetyl- beta- D-glucopyranoside), has been
      isolated together with 27 known compounds including flavonoids, caffeoylquinic
      acid derivatives, phenolics, and a monoterpenoid glucoside. Their structures were
      elucidated on the basis of spectroscopic data. Compounds and displayed
      significant xanthine oxidase inhibitory activity in a concentration-dependent
      manner, and compounds and showed more potent inhibitory activity, with IC50
      values ranging from 0.13 to 2.31 microM, than that of a positive control
      allopurinol (IC50=2.50 microM). The kinetic study indicated that and displayed
      competitive-type inhibition like that of allopurinol, while displayed a mixed
      type inhibition.

PMID- 16450296
TI  - Five new diels-alder type adducts from the stem and root bark of Morus mongolica.
AB  - Five new Diels-Alder type adducts, mongolicins A - E, and nine known compounds,
      mongolicin F, chalcomoracin, mulberrofuran T, mulberrofuran G, mulberrofuran F,
      albanol B, kuwanon O, mulberrofuran H and kuwanon H, were isolated from the stem
      and root bark of Morus mongolica. Their structures were determined by
      spectroscopic analysis and chiroptical methods. Among them, compounds and showed
      potent anti-inflammatory activities (inhibition of release of beta-glucuronidase
      from rat PMNs induced by PAF) with inhibitory ratios of 80.4% (P<0.05) and 77.0%
      (P<0.001) at a concentration of 10(-5) mol L-1. Compounds and were active as
      antioxidatives (inhibition of liver microsomal lipid peroxidation induced by Fe2+
      Cys system) with inhibitory ratios of 83.6% (P<0.05), 86.0% (P<0.05), and 63.0%
      (P<0.05) at a concentration of 10(-5) mol L-1.

PMID- 16450297
TI  - Cytotoxic arylnaphthalide lignan glycosides from the aerial parts of Phyllanthus
      taxodiifolius.
AB  - The arylnaphthalide lignan glycosides, taxodiifoloside, cleistanthoside A,
      cleistanthin A and cleistanthin A methyl ether, together with a triterpene,
      glochidone, have been isolated from the aerial parts of Phyllanthus
      taxodiifolius. The structures were established using spectral and chemical
      methods. Compounds and, as well as the derivatives and exhibited potent cytotoxic
      activities with GI50 values in the range of 10(-7)-10(-9) M in five cultured
      mammalian cancer cell lines while the new compound showed moderate activity (GI50
      in the order of 10(-6) M). Compounds and were inactive in all tested cell lines.

PMID- 16450298
TI  - A new neuroprotective compound of Ligustrum japonicum leaves.
AB  - A new secoiridoid glycoside characterized as (8 Z)-nuezhenide A along with five
      known glycosides, (8 E)-nuezhenide, (8 Z)-nuezhenide, oleonuezhenide,
      osmanthuside B and osmanthuside D, were isolated from the n-BuOH fraction of
      Ligustrum japonicum leaves. All six compounds significantly protected human
      neuroblastoma SH-SY5Y cells from 6-hydroxydopamine-induced neurotoxicity.

PMID- 16450299
TI  - Luteolin inhibits LPS-stimulated inducible nitric oxide synthase expression in BV
      2 microglial cells.
AB  - Overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS)
      acts as a neurotoxic effector in the central nervous system, resulting in
      neurodegenerative diseases. From the alcoholic extracts of Perilla frutescens, we
      have purified an inhibitor of NO production in lipopolysaccharide (LPS)-activated
      microglia by activity-guided purification. The active compound was identified as
      luteolin by spectral analysis. Luteolin inhibited the NO production in LPS
      activated microglia in a dose-dependent manner (IC50=6.9 microM). Luteolin also
      suppressed the degradation of I-kappaB-alpha, the expression of protein and mRNA
      of iNOS in LPS-activated microglia as observed in Western blot analysis and RT
      PCR experiments. Luteolin may have beneficial effects in the treatment of neuro
      inflammatory diseases through the inhibition of iNOS expression.

PMID- 16450300
TI  - Suppression of inducible nitric oxide synthase expression by diarylheptanoids
      from Alpinia officinarum.
AB  - Six diarylheptanoids were isolated from the rhizome of Alpinia officinarum
      (Zingiberaceae) as inhibitors of nitric oxide (NO) production in the
      lipopolysaccharide-activated macrophage cell line RAW 264.7. A double bond at C-4
      of the linker between two aromatic rings was found to be essential for activity.
      Furthermore, the active diarylheptanoids suppressed expression of the inducible
      NO synthase protein and mRNA. These results imply that the traditional use of
      Alpinia officinarum rhizome as anti-inflammatory drug may be explained, at least
      in part, by the inhibition of NO production in activated macrophages.

PMID- 16450301
TI  - Flavonoids from Artemisia copa with anti-inflammatory activity.
AB  - Bioactivity-guided fractionation of the dichloromethane and ethanol extracts from
      the aerial parts of Artemisia copa led to the isolation of the flavonoids
      spinacetin, jaceosidin, axillarin, penduletin, tricin and chrysoeriol. These
      compounds were studied for possible inhibitory activity on the generation of
      inflammatory mediators in a cell line of mouse macrophages (RAW 264.7) stimulated
      with lipopolysaccharide. Spinacetin and jaceosidin weakly inhibited nitric oxide
      production whereas all flavonoids reduced prostaglandin E2 levels to different
      extents. The most active flavonoid was jaceosidin that inhibited cyclooxygenase-2
      activity in a concentration-dependent manner with an IC50 value of 2.8 microM. In
      addition, the other flavonoids partially inhibited synovial phospholipase A2
      activity. These mechanisms may provide a basis for explaining the anti
      inflammatory activity of this plant.

PMID- 16450302
TI  - New cytotoxic 6-oxygenated 8,9-dihydrofurocoumarins, hedyotiscone A - C, from
      Hedyotis biflora.
AB  - Using the bioactivity-guided fractionation method, three new 6-oxygenated 8,9
      dihydrofurocoumarin-type compounds, hedyotiscones A, B, and C were isolated from
      the methanol extract of Hedyotis biflora together with seven known compounds. The
      structures of all isolated compounds were determined on the basis of mass and
      spectroscopic evidence. Compounds, oleanolic acid, and 6'-(beta-sitosteryl-3- O
      beta- D-glucopyranosidyl) pentadecanoate showed marginal cytotoxicity against Hep
      G2 cells (human liver cancer cells) with IC50 values of 14.4, 17.4, 4.9, 8.0, and
      9.2 microg/mL, respectively. Ursolic acid showed significant cytotoxicity against
      MDA-MB-231 cells (human breast carcinoma cells) with an IC50 value of 1.49
      microg/mL.

PMID- 16450303
TI  - Inhibitory effect of the norlignan 2-(2'-hydroxy-4',6'-dimethoxyphenyl)-5-[(E)
      propenyl]benzofuran from Krameria tomentosa on acetylcholine-induced relaxation
      of the rat aorta.
AB  - In this work, we studied the effect of the norlignan 2-(2'-hydroxy-4',6'
      dimethoxyphenyl)-5-[( E)-propenyl]benzofuran (DMPP) in the rat aorta. In aortic
      rings with intact endothelium, DMPP inhibited in a concentration-dependent manner
      the vasodilator effect produced by acetylcholine with an IC50 value of 31.2+/-6.3
      microM. DMPP also inhibited basal nitric oxide production. In endothelium-denuded
      vessels DMPP was without effect whereas superoxide dismutase (SOD) was effective
      in potentiating responses to the NO donor SIN-1. Contractile effects of carbachol
      in guinea-pig ileum and trachea were unaffected by DMPP. It is concluded that
      DMPP inhibits the endothelium-dependent relaxation induced by acetylcholine in
      the rat aorta without affecting receptor or smooth muscle cells function.
      Decreased nitric oxide production by endothelial cells seems to be the mechanism
      involved in the inhibitory effect of DMPP.

PMID- 16450304
TI  - Quercitrin: an antileishmanial flavonoid glycoside from Kalanchoe pinnata.
AB  - Quercitrin (quercetin 3- O-alpha- L-rhamnopyranoside), one of the constituents of
      the biologically active aqueous extract obtained from Kalanchoe pinnata, is
      demonstrated to be a potent antileishmanial compound (IC50 approximately 1
      microg/mL) with a low toxicity profile. This is the first time that
      antileishmanial activity is demonstrated for a flavonoid glycoside.

PMID- 16450305
TI  - Two new abietane diterpenoids from Salvia yunnanensis.
AB  - Two new abietane diterpenoids, yunnannin A and danshenol C, were isolated from
      Salvia yunnanensis together with ten known diterpenoids, danshenol A,
      przewalskin, tanshinone IIA, tanshinone I, crypotanshinone, 1,2
      dihydrotanshinone, tanshinlactone, 5,6-dehydrosugiol, 12-hydroxy-6,7-seco-8,11,3
      abietatriene-6,7-dial and phytol. Their structures were established based on
      spectroscopic data, chemical reactions and comparison with literature data.
      Compounds were tested for their antitumor activity in T-24, QGY, K562, Me180 and
      BIU87 cell lines. Compound showed inhibited growth of K562 (IC50=0.53 microg/mL),
      T-24 (IC50=7.94 microg/mL), QGY (IC50=4.65 microg/mL) and Me180 (IC50=6.89
      microg/mL) cell lines while compound was inactive. Compound showed moderate
      inhibitory activity on QGY (IC50=16.75 microg/mL) and Me180 (IC50=5.84 microg/mL)
      cells.

PMID- 16450306
TI  - New cytotoxic guttiferone analogues from Garcinia virgata from New Caledonia.
AB  - There are thirteen endemic species belonging to the genus Garcinia in New
      Caledonia. Among them, G. virgata is an evergreen tree mainly growing in the rain
      forests of this island. Fractionation of the cyclohexane extract of the stem bark
      of this plant produced the known benzophenones guttiferone E and xanthochymol,
      together with two new guttiferone analogues, namely guttiferones I and J. The
      structures of these benzophenones were mainly elucidated using 1D and 2D NMR
      spectroscopy. Compounds and were weakly cytotoxic on the KB cell line with IC50
      values of 4.70 and 5.0 microg/mL respectively.

PMID- 16450307
TI  - Differentiation of Dendrobium species used as "Huangcao Shihu" by rDNA ITS
      sequence analysis.
AB  - The genus Dendrobium Sw. is composed of 74 species and two varieties in China,
      and 32 species carry the name "Huangcao Shihu" on the herbal medicine market,
      making the identification of the origin of "Huangcao Shihu" difficult for
      consumers. Here, the ITS regions were sequenced and evaluated to differentiate
      the 18 Dendrobium species used as "Huangcao Shihu". Diversity in DNA sequences
      among various species was found with the inter-specific sequence divergence
      ranging from 3.2% to 37.9% in ITS1 and 5.0% to 26.6% in ITS2. Moreover, the
      variations within species were very low, ranging in sequence divergence from 0 to
      3.0% in ITS1 and 0 to 4.0% in ITS2. Therefore, these species could be easily
      distinguished at the DNA level. Furthermore, based on the divergent ITS regions,
      five pairs of species-specific primers were designed and used for the rapid PCR
      identification of five Dendrobium species listed in the Chinese Pharmacopoeia.

PMID- 16450308
TI  - Three new agarofuran sesquiterpenes reissantins F-H from Reissantia buchananii.
AB  - Three new agarofuran sesquiterpenes, reissantins F-H, were isolated from a
      methanol extract of Reissantia buchananii. Their structures as well as their
      relative stereochemistry were established on the basis of modern mass and
      spectroscopic methods. Compounds were assayed for cytotoxicity against HepG2 and
      Hep3B human liver cancer cell lines.

PMID- 16450309
TI  - Lack of correlation between the vitamin D receptor Fokl start codon polymorphism
      and bone mineral density in patients with Crohn's disease.
AB  - INTRODUCTION: We have examined the association of bone mineral density of
      patients with inflammatory bowel disease with a polymorphism in the gene encoding
      the vitamin D receptor. The thymine/cytosine (T/C) polymorphism in the first of
      two start codons can be defined by a restriction fragment length polymorphism
      using the restriction endonuclease FokI. Vitamin D receptor alleles containing
      the polymorphism have been denoted by f and alleles lacking the site by F.
      METHODS: We report on an association analysis of a basic population of 244
      caucasian patients with Crohn's disease. We have genotyped the FokI polymorphism
      of the VDR in these patients and associated the genotype with the bone mineral
      density of the lumbar spine and the femoral neck. RESULTS: In the cohort 42% of
      the patients were scored FF homozygous, 43.7% Ff heterozygous, and 14.3% ff
      homozygous. 14.4% of the FF patients, 18.8% of the Ff patients, and 9.7% of the
      ff patients had osteoporosis of the lumbar spine and 21.25% of the FF patients,
      25.3% of the Ff patients, and 18.5% of the ff patients had osteoporosis of the
      femoral neck. In this cohort no association between the genotype and the bone
      mineral density in the group as a whole nor when separated according to sex or
      age was found. CONCLUSIONS: In summary in our cohort no association of the FokI
      polymorphism and the BMD of the lumbar spine and femoral neck in patients with
      inflammatory bowel disease was found.

PMID- 16450310
TI  - Expression of the glucocorticoid receptor in the human adrenal cortex.
AB  - Glucocorticoids produced in the adrenal cortex act by binding to a specific
      intracellular protein, the glucocorticoid receptor (GR), which then modulates
      gene transcription in target tissues. Whether the adrenal cortex itself is a
      glucocorticoid target tissue has not been analyzed as yet. Since the presence of
      GR would be a prerequisite for such "intracortical" glucocorticoid action, this
      study was designed to analyze GR expression in the normal human adrenal gland
      using RT-PCR, Western blot, and immunohistochemistry. RT-PCR revealed the
      presence of GR mRNA in adrenal cortex as well as in NCIh295 cells. These results
      were confirmed at the protein level by Western blot employing a specific anti
      human GR antibody. Immunohistochemically, weak GR staining was observed in the
      adrenal medulla. In contrast, GR was strongly expressed in the adrenal cortex
      with the zona reticularis showing the most intense staining. Transfection of a GR
      responsive luciferase reporter gene into NCIh295 cells resulted in dexamethasone
      dependent induction of luciferase activity, indicating that GR is functional in
      this tissue. In this study, we show for the first time that GR is expressed in
      the human adrenal cortex. Its preferential expression in the zona reticularis may
      indicate a functional role in the regulation of adrenal androgen biosynthesis.

PMID- 16450311
TI  - Prevalence of impaired glucose tolerance 6 years after gestational diabetes.
AB  - AIM: Prevalence of glucose metabolism disorders in women six years after
      gestational diabetes in the index pregnancy (GDM). METHOD: 227 Caucasian women
      who developed GDM between 1995 and 1996 were investigated; 173 women (BMI 27.5+/
      6.0 kg/m2) received 75 g oGGT on average 5.8+/-2.0 years after delivery. RESULTS:
      Impaired glucose metabolism was found in 31.2%, IGT or IFG 19.1%, diabetes
      mellitus type 2 (DM2) 9.2%, diabetes mellitus type 1 (DM1) 2.3%, second GDM 0.6%.
      27.2% (BMI 25-29.9 kg/m2) were overweight, 23.1% suffered from obesity (BMI 30
      39.9 kg/m2) and 5.2% morbid obesity (BMI>or=40 kg/m2). In comparison to a healthy
      control group, women with DM2 at re-examination were: older in age (32.1+/-5.9
      vs. 29.1+/-4.8 years, p<0.05), had higher BMI (29.4+/-6.9 vs. 24.6+/-4.8 kg/m2,
      p<0.05), higher fasting blood glucose (6.5+/-1.9 vs. 5.2+/-0.9 mmol/l, p<0.05),
      earlier diagnosis of GDM (25+/-8 vs. 29+/-5 SSW, p<0.05), more frequent insulin
      therapy during pregnancy (75 vs. 24%) and had significantly higher insulin- and C
      peptide for all measures of the oGTT, whereas HbA1c was not different (4.9+/-0.5
      vs. 4.8+/-0.3%, n. s.). CONCLUSION: In an average of 5.8 years after the
      diagnosis of GDM, the majority of women still have chronic insulin resistance.
      One third has either IGT, IFG or diabetes mellitus. Therefore, a long term follow
      up is strongly recommended for women diagnosed with GDM.

PMID- 16450312
TI  - Structured diabetes therapy and education improves the outcome of patients with
      insulin treated diabetes mellitus. The 10 year follow-up of a prospective,
      population-based survey on the quality of diabetes care (the JEVIN Trial).
AB  - AIMS/HYPOTHESIS: JEVIN (Jena's St. Vincent Trial) is a prospective, 10 year
      follow-up, population-based survey of all insulin treated patients with type 1
      and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena
      (100,000 inhabitants), Thuringia, Germany. It aims to show the effects of
      implementation of the St. Vincent Declaration and to evaluate the effect of
      recent changes in the health care system and new treatment strategies. PATIENTS
      AND METHODS: 190 patients (83% of the target population), 244 patients (90%) and
      261 patients (90%) were studied in 1989/90, 1994/95 and 1999/2000, respectively.
      RESULTS: Up to 1994/95, the HbA1c of patients with type 1 diabetes mellitus
      increased (1994/95: 8.50+/-1.80% versus 1989/90: 7.83+/-1.60%, p=0.002). For
      patients with type 2 diabetes mellitus, it remained constant (9.01+/-2.06% versus
      9.17+/-1.60%, n. s.). During the period from 1994/95 to 1999/2000, there was a
      substantial improvement in the relative HbA1c of both, patients with type 1
      (7.62+/-1.55%, p<0.0001), and with type 2 diabetes (7.57+/-1.29%, p<0.0001). Up
      to 1999/2000, 87.7% of the patients with type 1 (1989/90: 0%, 1994/95: 73.2%) and
      96.6% of the patients with type 2 diabetes (1989/90: 0%, 1994/95: 89.7%)
      participated in TTP's. The incidence of acute and the prevalence of long-term
      complications remained constant. CONCLUSIONS: Results of the population-based,
      prospective trial to optimise patients' quality of diabetic control suggest: For
      patients with insulin treated type 2 diabetes mellitus, excellent treatment can
      be available by primary care physicians interested, educated and highly engaged
      in diabetes therapy. Moreover, structured diabetes therapy consisting of
      treatment and teaching programmes, regular self-monitoring, patients' insulin
      dose adjustment and patients' empowerment, should be offered to all patients with
      diabetes mellitus.

PMID- 16450313
TI  - Thyrotoxicosis-induced prinzmetal variant angina.
AB  - We describe a postmenopausal women with new onset of variant angina caused by
      thyrotoxicosis due to Graves' disease. During exercise bicycle ergometry at 50
      Watts, the patient developed typical angina with ST segment elevation in the
      precordial leads. A coronary angiogram revealed normal coronary arteries. Graves'
      disease with overt hyperthyroidism was diagnosed. After achieving an euthyroid
      state with administration of propylthiouracil, the symptoms resolved completely
      and the patient had a normal exercise capacity without electrocardiographic
      changes. Thus, we conclude that in patients with thyrotoxicosis, variant angina
      and normal coronary arteries, restoration of normal thyroid function may be
      curative.

PMID- 16450314
TI  - Diabetes insipidus due to herpes encephalitis in a patient with diffuse large
      cell lymphoma. A case report.
AB  - The major causes of central diabetes insipidus are neoplastic or infiltrative
      lesions of the hypothalamus or pituitary, severe head injuries and pituitary or
      hypothalamic surgery. Central diabetes insipidus caused by viral infections has
      been rarely reported in immunosuppressed patients, such as those with acquired
      immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year
      old woman suffering from diffuse large cell lymphoma, who developed hypotonic
      polyuria, hypernatriaemia and somnolence after the first course of chemotherapy
      with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine
      osmolarity and an undetectable vasopressin concentration. MRI revealed no
      pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes
      zoster infection. To the best of our knowledge this is the first description of
      central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS
      infection.

PMID- 16450315
TI  - Association of circulating antibodies against double-stranded and single-stranded
      DNA with thyroid autoantibodies in Graves' disease and Hashimoto's thyroiditis
      patients.
AB  - The occurrence of antinuclear antibody (ANA), rheumatoid factor (RF), antibodies
      to double-stranded DNA (anti-dsDNA) and to single-stranded DNA (anti-ssDNA) was
      investigated in 51 patients with autoimmune thyroid diseases (AITD), and in 25
      matched control subjects. In comparison with controls, the prevalence of anti
      dsDNA was 74.5% in AITD patients (p=0.0001), 82.0% in 39 hyperthyroid Graves'
      disease (GD) (p=0.0001), and 50.0% in 12 euthyroid Hashimoto's thyroiditis (HT)
      patients (p=0.0001). The prevalence of anti-ssDNA was 90.1% in AITD (94.8% in GD
      and 75% in HT; p=0.001). The concentration of both anti-dsDNA and anti-ssDNA were
      higher (p=0.002) in AITD, in GD (p=0.001), and in HT (p=0.01) patients than in
      controls. Two patients with AITD were identified as positive for ANA. RF was
      detected in 4 AITD patients. Positive correlation was noted between anti-dsDNA
      with T4 (p=0.001), T3 (p=0.002), thyroid peroxidase antibody (anti-TPO)
      (p=0.0001), and TSH (p=0.001) values but not with thyroglobulin antibody (anti
      Tg). Serum anti-ssDNA values were also correlated with T3 (p=0.0001), TSH
      (p=0.003), and anti-TPO (p=0.0001). However, by using a multiple regression
      analysis only anti-TPO remained associated with anti-dsDNA and both anti-Tg and
      anti-TPO with anti-ssDNA values. The predisposition to develop systemic
      autoimmune disorders is not influenced by thyroid hormones. The elevated
      prevalence of serum anti-dsDNA and anti-ssDNA in AITD patients points out that we
      must be aware of the risk for predisposition for the development of other
      systemic autoimmune diseases.

PMID- 16450316
TI  - Hormonal and metabolic evaluation in Down's syndrome: preliminary evidence for
      TSH dysregulation in hyperthyrotropinemic patients.

PMID- 16450317
TI  - Insulin glargine and educational intervention in patients with type 2 diabetes in
      clinical practice: long-term improvement in glycaemic control without weight
      gain.

PMID- 16450318
TI  - [Stroke and resources for urgent neurological attention: why arrive in time?].

PMID- 16450319
TI  - [Use of extra-hospital emergency systems in the treatment of acute stroke in the
      region of Murcia. Possible repercussions on the urgent care of stroke patients].
AB  - AIM: To examine the use of extra-hospital emergency systems in the urgent care of
      stroke patients in our region and their influence on the time required to reach
      hospital, the time needed to perform an urgent computerised axial tomography
      (CAT) scan and the delay in receiving attention from the specialist. PATIENTS AND
      METHODS: Samples were collected from 232 stroke patients out of the total number
      admitted to our hospitals. Data about the stroke were collected prospectively,
      and included the arrival time, the time required to perform the CAT scan and the
      time the specialist devoted to attending the patient. Data were also gathered
      about the different extra-hospital transport and emergency systems. A statistical
      analysis was performed to determine the effect of using the extra-hospital
      emergency procedures on the different variables. RESULTS: A total of 53.6% of
      patients arrived within the first three hours. 38.7% went straight to hospital,
      25% visited extra-hospital Emergency Services first, and 18.5% made a prior visit
      to Primary Care. 51.5% found their own way to the hospital and 46.7% arrived by
      ambulance. Mean time taken to perform an urgent CAT scan: 190.4 minutes; mean
      time required for specialist attention: 25.65 hours. The only statistically
      significant relation was the use of extra-hospital emergency systems and health
      care transport according to the type of stroke: both were more likely to be used
      in cases of haemorrhagic stroke. CONCLUSIONS: In hospitals in the Murcia region,
      the use of the extra-hospital emergency system and the means of transport
      utilised do not affect the time stroke patients take to reach hospital or the
      time needed to perform an urgent CAT scan or the delay in receiving attention
      from a specialist; the aetiology of the stroke does, however, influence the use
      of such services.

PMID- 16450320
TI  - [Cognitive performance of right-handed and left-handed persons on the Wechsler
      Adult Intelligence Scale (WAIS-III)].
AB  - AIM: To contribute to the knowledge of the cognitive differences existent between
      right-handed and left-handed evaluating the cognitive outcome in a group of
      adults right-handed and another group of left-handed of similar characteristic
      (age, gender, cultural level) by means of the Wechsler Adult Intelligence Scale
      (WAIS-III). SUBJECTS AND METHODS: Two groups were studied: one formed by 25 right
      handed (RHG) and another formed by 25 left-handed (LHG). None of those subject of
      the study presented mental deficiency neither neurological dysfunctions. The age
      stocking was of 24.28 years, with a range between 20 and 28 years. RESULTS: There
      are not differences in the intellectual quotient (verbal and performance), among
      the two groups. The LHG obtains worse results that the right-handed in speed of
      prosecution and in the subtests of arithmetic and key, while the RHG has obtained
      better results in the subtest of incomplete figures. CONCLUSIONS: The LHG has a
      cognitive yield similar to that of the RHG, with slight deficiencies in
      activities of visoperceptual component. It becomes necessary to continue
      deepening in the neuropsychological and cognitive differences between right
      handed and left-handed, since the cognitive outcome of the left-handed ones
      continues being a topic in discussion.

PMID- 16450321
TI  - [Frontal dysfunction in idiopathic Parkinson's disease].
AB  - INTRODUCTION: In his description of the disease in his original work, James
      Parkinson claimed that the 'senses remained intact', but later reports began to
      identify cognitive impairment that ranged from dementia to barely identifiable
      subclinical deteriorations. Research carried out in recent decades has revealed
      that cognitive disorders form part of the clinical symptoms of Parkinson's
      disease (PD) and point to the frontal lobes as being the most affected areas; a
      great deal of controversy, however, still surrounds their definition,
      epidemiology and pathology. AIM: To determine and classify the frontal deficits
      associated to this disease and to relate this cognitive performance with certain
      characteristics of the disease. SUBJECTS AND METHODS: The sample utilised in the
      study was made up of 222 subjects divided into two groups according to their
      diagnosis: 111 subjects with idiopathic PD and 111 control subjects. The
      neuropsychological examination was performed using the Frontal Assessment
      Battery, the copy of the Rey-Osterrieth complex figure and the digit test for
      determining frontal functioning. RESULTS AND CONCLUSIONS: We prove the existence
      of a frontal dysfunction that is characterised by impaired working memory, with
      visuospatial and executive dysfunction, which suggests greater involvement of the
      dorsolateral prefrontal cortex and cingulate. According to our findings, because
      working memory and visuospatial functioning are correlated to the motor status
      and the time elapsed since the onset of the disease, they could share the same
      underlying neuroanatomical foundations--the nigrostriatal denervation. This is
      not the case of executive function, which was not found to be related to the
      characteristics of the disease under study.

PMID- 16450323
TI  - [Nephrolithiasis and topiramate].
AB  - INTRODUCTION: Topiramate (TPM) is a new antiepileptic drug whose multiple
      mechanisms of action justify both its broad therapeutic spectrum and its
      increasingly widespread use in childhood epilepsy. TPM acts as a carbonic
      anhydrase inhibitor and, although this does not affect its effectiveness as an
      antiepileptic, it does account for certain side effects such as nephrolithiasis.
      The frequency of nephrolithiasis secondary to TPM in childhood is unknown and we
      have only found reports of five cases in children. CASE REPORTS: We describe two
      cases of medication-resistant infantile epilepsy--a 3-year-old female with
      Dravet's syndrome and a male aged 4.5 years with Lennox-Gastaut syndrome. In both
      cases the decision was made to introduce TPM as add-on therapy after a prolonged
      therapeutic programme; a high degree of effectiveness was achieved in both
      patients. Nevertheless, the two patients developed nephrolithiasis secondary to
      TPM, which in the second case was related to the simultaneous treatment with
      adrenocorticotropic hormone (ACTH), while no known favouring factor was found in
      the first patient. CONCLUSIONS: We outline the physiopathogenic mechanism
      explaining nephrolithiasis secondary to TPM, the risk factors involved and the
      therapeutic and preventive options available in dealing with this side effect,
      which occurs in a low percentage of cases but which usually means stopping
      administration of this therapy. We therefore believe it necessary to analyse the
      risk factors for nephrolithiasis before prescribing the drug and we suggest that
      generalised preventive measures should be implemented, especially in children who
      are carriers of encephalopathies or conditions that reduce mobility.

PMID- 16450322
TI  - [Unusual variants of Guillain-Barre syndrome in infancy].
AB  - AIMS: To identify unusual variants within a paediatric population of patients
      with Guillain-Barre syndrome (GBS), to determine the frequency of their
      occurrence and to describe their clinical and electrophysiological
      characteristics. PATIENTS AND METHODS: The medical records of 179 patients
      diagnosed with GBS were reviewed. Those who strictly satisfied the Asbury
      criteria were excluded. RESULTS: Twenty patients, with a mean age of 7.6 years at
      the onset of symptoms, presented the following clinical variants: multiple
      cranial polyneuropathy (4 cases), Miller Fisher syndrome (MFS) (3 cases),
      pharyngeal-cervical-brachial palsy (PCBP) (2 cases), combined MFS and PCBP (3
      cases), paraparesis (4 cases), palpebral ptosis without ophthalmoplegia (1 case),
      ophthalmoplegia without ataxia (1 case), paresis of the abducent nerve with
      paresthesias (1 case), and saltatory (1 case). Albuminocytologic dissociation was
      reported in 77.8% of patients and neuroconduction with a demyelinating pattern
      was noted in 75%. Patients progressed favourably in 94.4% of cases. CONCLUSIONS:
      In our study, 11.2% of a population of children with GBS presented unusual
      variants and did not meet the criteria established by Asbury et al. Recognising
      these variants of GBS in patients with complex pictures such as those described
      here enables therapy to be established quickly. The question remains as to
      whether these variants represent a clinical response to different antibodies or
      to a regional susceptibility of the host.

PMID- 16450324
TI  - [Oxcarbazepine in the treatment of epilepsy. A review and update].
AB  - AIM: To review and update the most important information concerning the mechanism
      of action, efficacy, safety and clinical use of oxcarbazepine (OXC), one of the
      new antiepileptic drugs (AED). DEVELOPMENT: In humans, OXC is rapid and
      extensively metabolized to its pharmacologically active 10-monohydroxy metabolite
      (MHD). OXC is a molecule derived from carbamazepine (CBZ), but these two drugs
      showed differences in their mechanism of action. OXC pharmacokinetics presents
      advantage over CBZ: in contrast with CBZ, OXC does not show autoinduction, the
      OXC dose-MHD serum concentration relationship displays a linear kinetics over the
      therapeutic dose range, and the frequency of drug-drug interactions is lower. So,
      we can establish standardized dose regimen and titration schedules in monotherapy
      and polytherapy. OXC shows better tolerability and safety than CBZ, in part at
      consequence of absence of 10-11-epoxi metabolites from CBZ. The better safety
      profile of OXC is reflected in less adverse drug reactions incidence, lower
      patient risk in overdosing, absence of reported cases of agranulocytosis or
      aplastic anemia, scarce cases founded of cardiotoxicity and lower risk of
      neurotoxicity. Common side effects of OXC are nausea, dizziness, vomiting,
      fatigue, diplopia and somnolence. During treatment with OXC must pay attention to
      development of hyponatremia, neurotoxicity or cutaneous hypersensitivity
      reactions. OXC is approved for use in infants. OXC is indicated for use as
      monotherapy or adjunctive therapy in the treatment of partial seizures with or
      without secondarily generalized seizures in adults and in children age 6 and
      over. CONCLUSIONS: OXC showed important advances on safety and pharmacological
      properties for administration to adults and infants. OXC has similar clinical
      antiepileptic efficacy than older AED in the treatment of partial seizures, and
      it is recommended as a treatment of choice for partial seizures by several
      international guidelines.

PMID- 16450325
TI  - [Cluster headache: its diagnosis, pathophysiology and treatment].
AB  - INTRODUCTION: Cluster headache (CH) is the most frequent subtype of trigeminal
      headache with autonomic symptoms (THAS); yet, despite its characteristic clinical
      profile it remains poorly understood and badly controlled. AIMS: To identify the
      correct diagnostic criteria of CH and the respective differential diagnoses, as
      well as to gain an understanding of the pathophysiology of CH, its treatment and
      prognosis by means of a review of the literature. DEVELOPMENT AND CONCLUSIONS: CH
      is a condition that is characterised by the presence of sharp, or extremely
      sharp, unilateral pain that is short-lasting and usually located in the
      retroocular and/or temporal region; it is also accompanied by ipsilateral
      autonomic symptoms (mainly conjunctival injection). CH can be differentiated from
      other THAS by the frequency with which it appears and the amount of time the pain
      lasts (the average is less than five attacks a day lasting from 30 minutes to 3
      hours), as well as the response to treatment. A number of neuronal pathways are
      involved in the pathophysiology of CH. It has been suggested that the activation
      of the trigeminovascular and the parasympathetic systems, together with the
      dysfunction of the cranial sympathetic system, are involved in this condition.
      Moreover, there is evidence to support the role of functional and structural
      alterations in the hypothalamus. Treatment of CH is based on the proper
      pharmacological implementation of abortive, transitional and prophylactic
      therapies. Surgical interventions are recommended in patients with strictly
      unilateral pain in the ophthalmic division of the trigeminal nerve who are
      resistant to multiple therapies, and/or offer a poor response and/or
      contraindications to pharmacological treatment. Factors related to genetics,
      brain functioning or the environment, as well as the way the symptoms present
      (episodic or chronic), determine the prognosis of CH.

PMID- 16450326
TI  - [Differential diagnosis between osteogenesis imperfecta and child abuse: a
      dilemma with legal implications in Neuropaediatrics].

PMID- 16450327
TI  - [Subcortical crossed aphasia: a case report].

PMID- 16450329
TI  - [Scopolamine poisoning ('burundanga'): loss of the ability to make decisions].

PMID- 16450331
TI  - Evaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast
      agents for MR imaging.
AB  - Different generations of Gd(III)DTPA-terminated poly(propylene imine) dendrimers
      {G1 [n = 4 Gd(III) ions per molecule], G3 (n = 16) and G5 (n = 64)} and reference
      Gd(III)DTPA complex [G0 (n = 1)] were characterized in terms of (i) longitudinal
      (r1) and transverse (r2) relaxivities in mouse blood plasma, (ii) concentration
      detection limits in vitro and (iii) in vivo contrast-enhanced MR imaging (CE-MRI)
      in mice at 1.5 T. Serial and dynamic CE-MRI were performed to monitor the
      distribution of MRI contrast agent in the heart, arteries, renal system, liver,
      spleen, bladder and tumor periphery. The relaxivities increased non-linearly with
      molecular weight (for G0 ionic r1 = 8.1 mM(-1) s(-1) and ionic r2 = 8.6 mM(-1) s(
      1) to G5 19.3 and 25.0, respectively). The minimal detectable dendrimer
      concentration was more than two orders of magnitude lower for G5 (8.1 x 10(-8) M)
      than for G0 (3.1 x 10(-5) M). Sub-millimeter-sized blood vessels were well
      visualized with serial CE-MRI with each contrast agent. Dynamic CE-MRI showed
      timely renal clearance for all contrast agents, but a stronger and a prolonged
      blood signal enhancement for the higher generations of the dendritic contrast
      agent. Moreover, G0 and G1 showed a rapid tumor wash-in and wash-out, whereas G3
      and G5 displayed a more gradual and prolonged tumor wash-in. In conclusion, both
      G0 and dendritic contrast agents G1, G3 and G5 are well suited for non-tissue
      specific MRI of sub-millimeter-sized blood vessels and evaluating tumor
      microcirculatory characteristics in mice. Higher generations of dendritic
      contrast agents display lower concentration detection limits, which suggests
      their future use for molecular imaging.

PMID- 16450332
TI  - Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging.
AB  - In the field of MR imaging and especially in the emerging field of cellular and
      molecular MR imaging, flexible strategies to synthesize contrast agents that can
      be manipulated in terms of size and composition and that can be easily conjugated
      with targeting ligands are required. Furthermore, the relaxivity of the contrast
      agents, especially for molecular imaging applications, should be very high to
      deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as
      liposomes or micelles, have been used extensively in recent decades as drug
      carrier vehicles. A relatively new and promising application of lipidic
      nanoparticles is their use as multimodal MR contrast agents. Lipids are
      amphiphilic molecules with both a hydrophobic and a hydrophilic part, which
      spontaneously assemble into aggregates in an aqueous environment. In these
      aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster
      together and the hydrophilic parts face the water. In the low concentration
      regime, a wide variety of structures can be formed, ranging from spherical
      micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a
      shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum
      dots or perfluorocarbon emulsions can be solubilized using this approach. MR
      detectable and fluorescent amphiphilic molecules can easily be incorporated in
      lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to
      lipidic particles by incorporating lipids with a functional moiety to allow a
      specific interaction with molecular markers and to achieve accumulation of the
      particles at disease sites. In this review, an overview of different lipidic
      nanoparticles for use in MRI is given, with the main emphasis on Gd-based
      contrast agents. The mechanisms of particle formation, conjugation strategies and
      applications in the field of contrast-enhanced, cellular and molecular MRI are
      discussed.

PMID- 16450333
TI  - Tenascin C and annexin II expression in the process of pancreatic carcinogenesis.
AB  - Tenascin C (TNC) is a component of the provisional extracellular matrix (ECM)
      that characterizes solid tumours. Cell surface annexin II is a high-affinity
      receptor for large TNC splice variants. The aim of this study was to analyse
      whether TNC and annexin II play a role in the development of pancreatic ductal
      adenocarcinoma (PDAC). PDAC is characterized by a rich ECM populated by
      pancreatic stellate cells, which play a crucial role in pancreatic desmoplasia.
      The mRNA and protein levels of TNC and of annexin II were analysed in pancreatic
      tissues by DNA array, quantitative reverse transcriptase-polymerase chain
      reaction (QRT-PCR) and immunohistochemistry. TNC large splice variants were
      detected by RT-PCR. Enzyme linked immunosorbent assay (ELISA) was used to measure
      TNC levels in serum and culture supernatants. TNC and annexin II mRNA levels were
      significantly higher in pancreatic cancer tissues than in the normal pancreas.
      TNC expression was detected with increased frequency in the progression from
      PanIN-1 lesions to PDAC, and a parallel switch from cytoplasmic to cell surface
      expression of annexin II was observed. Large TNC transcripts were found in
      pancreatic cancer and in chronic pancreatitis, but not in the normal pancreas.
      TNC expression was demonstrated in pancreatic stellate cells, where it could be
      induced by tumour necrosis factor alpha (TNFalpha), transforming growth factor
      beta1 (TGF-beta1) and by cancer cell supernatants supplemented with TGF-beta1. In
      conclusion, the expression of TNC and cell surface annexin II increases in the
      progression from low-grade PanIN lesions to pancreatic cancer. Pancreatic
      stellate cells are identified as a source of TNC in pancreatic tissues, possibly
      under the influence of soluble factors released by the tumour cells.

PMID- 16450334
TI  - Development of testicular inflammation in the rat involves activation of
      proteinase-activated receptor-2.
AB  - Mast cells are involved in early events crucial to inflammation and autoimmune
      disease. Recently, proteinase-activated receptor-2 (PAR(2)), a G-protein coupled
      receptor important to injury responses, was shown to be activated by mast cell
      tryptase. To investigate whether mast cells and PAR(2) are involved in the
      development and/or aggravation of testicular inflammation, we studied acute and
      chronic inflammatory models in the rat. In normal testes, PAR(2) was detected
      immunohistochemically in macrophages, in peritubular cells (PTCs) and in
      spermatid acrosomes. In experimentally induced autoimmune orchitis (EAO), PAR(2)
      was strongly upregulated in macrophages and peritubular-like cells, forming
      concentric layers around granulomas. Mast cells increased 10-fold in number, were
      more widely distributed throughout the interstitial tissue, and were partially
      degranulated. Isolated PTCs expressed functional PAR(2), responded to PAR(2)
      activation by phosphorylating extracellular signal-regulated kinases 1/2 (ERK1/2)
      and activating protein kinase c, and increased intracellular Ca(2+)
      concentrations as well as monocyte chemoattractant protein-1 (MCP-1),
      transforming growth factor beta(2) (TGFbeta(2)), and cyclooxygenase-2 (COX-2)
      mRNA expression. Expression of these inflammatory mediators, together with iNOS,
      also increased significantly in testes 50 days after EAO. In vivo, expression of
      cytokines and inflammatory mediators was upregulated after injection of
      recombinant tryptase (MCP-1, TGFbeta(2), and COX-2) and a specific PAR(2) peptide
      agonist (MCP-1, TGFbeta(2)) in the testis after 5 h. These results suggest that
      PAR(2) activation elicited on PTCs by mast cell tryptase contributes to acute
      testicular inflammation and that this pathogenetic mechanism may also play a role
      in autoimmune orchitis.

PMID- 16450335
TI  - The HAUSP gene plays an important role in non-small cell lung carcinogenesis
      through p53-dependent pathways.
AB  - Herpesvirus-associated ubiquitin-specific protease (HAUSP) directly stabilizes
      the tumour suppressor p53 by de-ubiquitination. Therefore, the HAUSP gene might
      play an important role in carcinogenesis. In this paper, HAUSP expression and p53
      gene status have been studied in relation to the expression of p53 target genes
      in 131 patients with non-small cell lung cancer (NSCLC). p53 gene status was
      evaluated by polymerase chain reaction-single-strand conformation polymorphism
      (PCR-SSCP) followed by sequencing. Quantitative reverse-transcription polymerase
      chain reaction (RT-PCR) was performed to evaluate the gene expression of HAUSP,
      p21, and bax. Immunohistochemistry was performed to evaluate the protein
      expression of p53, HAUSP, mdm2, p21, and bax. Fifty-nine carcinomas (45.0%)
      showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of
      p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower
      in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the
      frequency of p53 mutation was significantly higher in squamous cell carcinomas
      than in adenocarcinomas (p = 0.0461). There was no significant difference in
      HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas
      (71.0%) showed either mutant p53 or reduced HAUSP expression. The down-regulation
      of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in
      tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53).
      Furthermore, p21 and bax protein expression was significantly lower in tumours
      with either mutant p53 or reduced HAUSP expression than in tumours with both wild
      type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively).
      In addition, the simultaneous evaluation of both HAUSP expression and p53 gene
      status was a significant indicator of poor prognosis in adenocarcinoma patients
      (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP
      gene expression may play an important role in NSCLC carcinogenesis, especially in
      adenocarcinomas, through p53-dependent pathways.

PMID- 16450336
TI  - Effect of the intracellular localization of a Gd-based imaging probe on the
      relaxation enhancement of water protons.
AB  - Gd-HPDO3A has been internalized into rat hepatocarcinoma cells in the cytoplasm
      (by electroporation) or in intracellular vesicles (by pinocytosis), respectively.
      In the former case, the observed relaxation rates are likely dependent upon the
      amount of internalized paramagnetic complex, whereas in the latter case the
      relaxation enhancement is "quenched" to a plateau value (about 3 s(-1)) when the
      entrapped amount of Gd-chelate is higher than 1 x 10(10) Gd/cell. The observed
      behavior has been accounted in terms of a theoretical treatment based on
      equations formally derived by Labadie et al. (J Magn Reson B 1994;105:99-102). On
      this basis, entrapment into intracellular vesicles has been treated as a three
      site water exchange (extracellular/cytoplasm/vesicle compartments), whereas the
      cell pellets containing the paramagnetic agent spread out in the cytoplasm can be
      analyzed by a two-site exchange system.

PMID- 16450338
TI  - Multinuclear NMR and MRI studies of the maturation of pig articular cartilage.
AB  - The maturation of pig articular cartilage was followed by (2)H in-phase double
      quantum filtered (IP-DQF) spectroscopic MRI, (1)H T(2) MRI, and (23)Na DQF and
      triple quantum filtered MRS. The results all lead to the conclusion that the
      order and density of the collagen fibers in articular cartilage increase from
      birth to maturity. At birth, both (2)H IP-DQF signal and (1)H T(2) were
      homogeneous throughout the cartilage and their values independent of the
      orientation of the plug relative to the magnetic field. At maturation, the (2)H
      IP-DQF spectrum near the bone is composed of two pairs of quadrupolar split
      satellites and the (1)H T(2) relaxation is biexponential, indicating the presence
      of two groups of collagen fibers. The (2)H satellites are orientation dependent,
      indicating that the two groups of fibers are well ordered at maturation. The fast
      component of (1)H T(2) is also orientation dependent and thus we have concluded
      that this component results from residual dipolar interaction, while the slow
      T(2) component in mature cartilage, as well as the T(2) relaxation in immature
      cartilage, is governed by other mechanisms.

PMID- 16450339
TI  - Retrospective gating for mouse cardiac MRI.
AB  - Cardiac MR imaging in small animals presents some difficulties due to shorter
      cardiac cycles and smaller dimensions than in human beings, but prospectively
      gated techniques have been successfully applied. As with human imaging, there may
      be certain applications in animal imaging for which retrospective gating is
      preferable to prospective gating. For example, cardiac imaging in multiple mice
      simultaneously is one such application. In this work we investigate the use of
      retrospective gating for cardiac imaging in a mouse. Using a three-dimensional
      imaging protocol, we show that image quality with retrospective gating is
      comparable to prospectively gated imaging. We conclude that retrospective gating
      is applicable for small animal cardiac MRI and show how it can be applied to the
      problem of cardiac MRI in multiple mice.

PMID- 16450341
TI  - Primary tumour genetic alterations and intra-tumoral heterogeneity are maintained
      in xenografts of human colon cancers showing chromosome instability.
AB  - Evaluation of the role of clonal heterogeneity in colon tumour
      sensitivity/resistance to drugs and/or in conferring metastatic potential
      requires an adequate experimental model in which the tumour cells maintain the
      initial genetic alterations and intra-tumoral heterogeneity through maintenance
      of the genetic clones present in the initial tumour. Therefore, we xenografted
      subcutaneously into nude mice seven human colonic tumours (from stages B1 to D)
      that showed chromosome instability and transplanted them sequentially for up to
      14 passages. Maintenance after xenografting of the genetic alterations present in
      the initial tumours was scored by allelotype studies targeting 45 loci localized
      on 18 chromosomes. We show that xenografting does not alter the genetic or the
      histological profiles of the tumours even after 14 passages. Screening of the
      entire genome of one tumour by comparative genome hybridization also showed
      overall stability of the alterations between the initial and the xenografted
      tumour. In addition, intra-tumoral heterogeneity was maintained over time,
      suggesting that no clonal selection occurred in the nude mice. The observation
      that some loci showed partial allelic imbalance in the initial tumour but loss of
      heterozygosity after the first passage in nude mice when all the normal cells
      were lost may allow identification of interesting genetic defects that could be
      involved in tumour expansion. Thus, sequential xenografts of colon tumours will
      provide a powerful model for further study of tumour clonality and for the
      identification of genetic profiles responsible for differential resistance to
      therapeutic treatments. Our data also suggest that tumour expansion can result
      from alterations in several distinct genetic pathways.

PMID- 16450340
TI  - Rasagiline improves quality of life in patients with early Parkinson's disease.
AB  - The objective of this study was to determine the effects of rasagiline as
      monotherapy on quality of life (QOL) in patients with early Parkinson's disease
      (PD). Rasagiline, a potent, second-generation, irreversible, selective monoamine
      oxidase B inhibitor improves PD symptoms in patients with early PD. Patients with
      early untreated PD were randomly assigned to once-daily rasagiline 1 mg/day,
      rasagiline 2 mg/day, or placebo in a 6-month, double-blind trial (n=404). At the
      end of 6 months, patients entered the preplanned, active-treatment phase in which
      those receiving 1 mg/day and 2 mg/day of rasagiline continued on their previously
      assigned dosages and those receiving placebo switched to rasagiline 2 mg/day,
      while maintaining blinding to treatment assignments. QOL was measured with the
      Parkinson's Disease Quality of Life questionnaire (PDQUALIF) at 0, 14, 26, and 52
      weeks after randomization. Analysis of the change in PDQUALIF scores from
      baseline to 6 months showed adjusted treatment effects (with 95% confidence
      interval) favoring rasagiline over placebo of -2.91 units (-5.19, -0.64, P=0.01)
      for the 1 mg/day group and -2.74 units (-5.02, -0.45, P=0.02) for the 2 mg/day.
      Subscore analysis attributed most of this benefit to the self-image/sexuality
      domain. At 12 months (n=266), with all groups receiving rasagiline for at least 6
      months, no significant differences in PDQUALIF scores were seen between groups.
      Rasagiline improved QOL compared with placebo. This QOL improvement appears to be
      accounted for primarily by the symptomatic benefit of rasagiline.

PMID- 16450342
TI  - Measuring the effect of husband's health on wife's labor supply.
AB  - A sizable proportion of women remain married well into late life and an
      increasing proportion of them participate in the labor force. Since women tend to
      marry men older than themselves and men tend to experience serious illnesses at
      younger ages than women, women frequently witness declining health in their
      husbands. This is likely to affect a wife's labor-leisure trade-off in offsetting
      ways. Prior studies have not sought to disentangle the effect of a husband's poor
      health on his wife's reservation wage from the income effect of his ill health.
      We argue that, if we control for husband's earnings, the coefficient of husband's
      health in models of his wife's labor force participation (and hours of work) will
      reflect, in part, her preference over whether to decrease her labor supply to
      provide health care for her husband or whether to instead increase it to purchase
      this care in the market. However, husband's earnings are likely to be endogenous
      in these models due to unobserved characteristics common to husbands and wives.
      We find that the estimated effect of husband's health depends on whether we
      instrument for husband's earnings and on the health measure used. This is
      indicative of the importance of using a variety of health measures and
      controlling for husband's earnings, and their endogeneity, in future research on
      the effect of husband's health on wife's labor supply.

PMID- 16450343
TI  - Targeting histone deacetylase in cancer therapy.
AB  - Histone deacetylase (HDAC) is recognized as one of the promising targets for
      cancer treatment as many HDAC inhibitors have entered clinical trials for both
      solid and liquid tumors. Nevertheless, the mechanisms underlying the
      antiproliferative effects of HDAC inhibitors remain elusive. Although they have
      been shown to regulate the transcription of a defined set of genes through
      chromatin remodeling, increasing evidence suggests that modifications of the
      epigenetic histone code may not be the primary mechanism for HDAC inhibitor
      mediated growth inhibition and apoptosis in cancer cells. While histones still
      represent a primary target for the physiological function of HDACs, the antitumor
      effect of HDAC inhibitors might also be attributed to transcription-independent
      mechanisms by modulating the acetylation status of a series of nonhistone
      targets. Also noteworthy is the effect of HDAC inhibitors on Akt downregulation
      through the alteration of protein phosphatase 1 (PP1) complex formation. To
      provide an overview of the use of HDAC inhibitors in cancer treatment, this
      review addresses the following subjects: (1) the physiological relevance of HDAC
      mediated acetylation of histone and nonhistone substrates, (2) the chemical
      biology of HDACs and development of a novel class of HDAC inhibitors, and (3) the
      protein acetylation-independent effect of HDAC inhibitors on the activation
      status of signaling kinases.

PMID- 16450344
TI  - Partial deficit of pantothenate kinase 2 catalytic activity in a case of tremor
      predominant neurodegeneration with brain iron accumulation.
AB  - We describe an atypical case of pantothenate kinase-associated neurodegeneration
      (PKAN) in which slowly progressive arm tremor was the predominant symptom
      beginning at the age of 25, with late-onset dystonia and dysarthria developing at
      the age of 50. Compound heterozygous mutations resulting in missense amino acid
      substitutions G521R and I529V were identified in the pantothenate kinase (PANK2)
      gene. We demonstrate that while the G521R mutation results in an unstable and
      inactive protein, the previously unreported I529V substitution has no apparent
      effect on the stability or catalytic activity of PanK2. The phenotype that
      results from this combination of mutations suggests that atypical presentations
      of PKAN may arise from partial deficits in PanK2 catalytic activity.

PMID- 16450345
TI  - Structural variants in the vesicular monoamine transporter do not contribute to
      sporadic Parkinson's disease.

PMID- 16450346
TI  - Fetomaternal hemorrhage in relation to chorionic villus sampling revisited.
AB  - OBJECTIVE: To investigate whether chorionic villus sampling (CVS) results in a
      proportional increase of alpha-fetoprotein (AFP) and fetal red cells in maternal
      blood. METHODS: Blood samples were collected before and after CVS. The AFP
      concentration was measured and supervised automated microscopy of Kleihauer-Betke
      slides was applied to quantify fetal red cells. RESULTS: AFP analysis was
      performed in 53 paired samples and automated microscopic scanning in 59 paired
      samples. Median AFP concentrations before and after CVS were 12.0 microg/L (range
      6.4-36.4) and 18.7 microg/L (range 8.2-668.9), respectively, indicating a
      significant increase (p < 0.0001). Median numbers of fetal red cells detected
      before and after CVS were 0 (range 0-36) and 0 (range 0-31), respectively. No
      significant increase of fetal cells was observed (p = 0.72). The delta (Delta)
      fetal red cells and the Delta AFP correlated poorly (rho = -0.22, p = 0.11). The
      amount of villi correlated moderately with the Delta AFP (rho = 0.32, p = 0.02)
      and did not correlate with the Delta fetal red cells (rho = -0.11, p = 0.43).
      CONCLUSIONS: Although the AFP concentration after CVS increased, no increase of
      fetal red cells was detected. These findings suggest that CVS results in a
      leakage of proteins due to placental tissue damage, rather than increased
      trafficking of fetal cells.

PMID- 16450347
TI  - Reliability and validity of the International Cooperative Ataxia Rating Scale: a
      study in 156 spinocerebellar ataxia patients.
AB  - To evaluate the efficacy of treatments in spinocerebellar ataxias (SCAs),
      appropriate clinical scales are required. This study evaluated metric properties
      of the International Cooperative Ataxia Rating Scale (ICARS) in 156 SCA patients
      and 8 controls. ICARS was found to be a reliable scale satisfying accepted
      criteria for interrater reliability, test-retest reliability, and internal
      consistency. Although validity testing was limited, we found evidence of validity
      of ICARS when ataxia disease stages and Barthel index were used as external
      criteria. On the other hand, our study revealed two major problems associated
      with the use of ICARS. First, the redundant and overlapping nature of several
      items gave rise to a considerable number of contradictory ratings. Second, a
      factorial analysis showed that the rating results were determined by four
      different factors that did not coincide with the ICARS subscales, thus
      questioning the justification of ICARS subscore analysis in clinical trials.

PMID- 16450348
TI  - De novo monosomy 9p24.3-pter and trisomy 17q24.3-qter characterised by microarray
      comparative genomic hybridisation in a fetus with an increased nuchal
      translucency.
AB  - OBJECTIVES: Increased nuchal translucency (NT) during the first trimester of
      pregnancy is a useful marker to detect chromosomal abnormalities. Here, we report
      a prenatal case with molecular cytogenetic characterisation of an abnormal
      derivative chromosome 9 identified through NT. METHODS: Amniocentesis was
      performed because of an increased NT (4.4 mm) and showed an abnormal de novo
      46,XX,add(9)(p24.3) karyotype. To characterise the origin of the small additional
      material on 9p, we performed a microarray comparative genomic hybridisation
      (microarray CGH) using a genomic DNA array providing an average of 1 Mb
      resolution. RESULTS: Microarray CGH showed a deletion of distal 9p and a trisomy
      of distal 17q. These results were confirmed by FISH analyses. Microarray CGH
      provided accurate information on the breakpoint regions and the size of both
      distal 9p deletion and distal 17q trisomy. The fetus was therefore a carrier of a
      de novo derivative chromosome 9 arising from a t(9;17)(p24.3;q24.3) translocation
      and generating a monosomy 9p24.3-pter and a trisomy 17q24.3-qter. CONCLUSION:
      This case illustrates that microarray CGH is a rapid, powerful and sensitive
      technology to identify small de novo unbalanced chromosomal abnormalities and can
      be applied in prenatal diagnosis.

PMID- 16450349
TI  - Nuchal translucency measurements are highly correlated in both mono- and
      dichorionic twin pairs.
AB  - OBJECTIVES: To establish the distribution of serological and ultrasound first
      trimester Down syndrome markers in twins and identify correlations of
      significance for risk calculation. METHODS: Nuchal translucency (NT), PAPP-A and
      betahCG data were extracted from 181 twin pregnancies (31 mono- and 150
      dichorionic) with a normal outcome. All pregnancies were consecutively and
      prospectively included and examined in the Copenhagen First-Trimester Study. The
      variance of the sum and the difference of log MoM NT values in twin pairs was
      used to calculate the correlation. RESULTS: The serological markers did not
      correlate and were nearly twice the value seen in singleton pregnancies with a
      median PAPP-A MoM of 2.14 and a median free betahCG MoM of 2.06. Chorionicity was
      not found to influence the level of biochemical markers. In all twin pairs (r =
      0.343, p < 0.001, F-test), as well as mono- (r = 0.404, p = 0.011, F-test) and
      dichorionic twins (r = 0.316, p < 0.001, F-test) there was a significant
      correlation between log MoM NT in each pair. CONCLUSION: As the NT values of
      fetuses in subsequent pregnancies from the same woman do not correlate, the
      correlation between NTs in twins reflects that the NT is influenced by placental
      and maternal factors specific for the particular pregnancy, for example, nutrient
      supply or vascularisation. The correlation may be useful to improve the precision
      of the prenatal risk assessment for Down syndrome in first-trimester twin
      pregnancies. The serological markers were elevated in the examined twins as
      previously described.

PMID- 16450350
TI  - Molecular characterisation of a prenatally diagnosed 5q15q21.3 deletion and
      review of the literature.
AB  - BACKGROUND: Ultrasound examination performed on a 32-year old woman at 30 weeks'
      gestation showed the presence of fetal malformations. Amniocentesis was
      performed. METHODS AND RESULTS: Cytogenetic analysis of cultured amniocytes
      revealed an interstitial deletion of the long arm of chromosome 5. Molecular
      studies confirmed that the deletion included the 5q15-21.3 region and was 14 Mb
      in size. Therefore, the karyotype was: 46,XY,del(5)(q15q21.3). In addition,
      analysis of polymorphic DNA markers showed that the deletion was of paternal
      origin. CONCLUSIONS: The pregnancy was terminated at 34 weeks' gestation. At
      autopsy, the fetus displayed dysmorphic features, thin limbs and renal
      abnormalities. The clinical findings observed in the fetus as well as in 20 cases
      reported previously allowed us to further delineate the phenotype of such
      interstitial 5q15q21.3 deletions.

PMID- 16450351
TI  - Prenatal findings in four consecutive pregnancies with fetal Pierson syndrome, a
      newly defined congenital nephrosis syndrome.
AB  - OBJECTIVE: To describe the prenatal findings in Pierson syndrome, a newly defined
      autosomal recessive entity, comprising congenital nephrotic syndrome (CNS) with
      diffuse mesangial sclerosis and distinct eye abnormalities due to LAMB2
      mutations. METHODS: Serial prenatal ultrasound examinations were performed in
      four consecutive pregnancies affected by Pierson syndrome in the same family.
      LAMB2 mutations were demonstrated in retrospect by direct sequencing of the gene
      in the newborn index patient and three abortuses. RESULTS: Fetal ultrasound
      consistently revealed marked renal hyperechogenicity associated with variable
      degree of pyelectasis. These features were detectable by 15 weeks of gestation in
      all fetuses. Hydrops fetalis due to severe hypalbuminemia demonstrated by
      chordocentesis occurred in one fetus. Placentas were significantly enlarged.
      Development of oligohydramnios indicated prenatal decline of renal excretory
      function. Anencephaly was detected in another fetus with molecularly proven
      Pierson syndrome at 12 weeks of gestation. CONCLUSION: We conclude that Pierson
      syndrome has to be considered in the differential diagnosis of nephrotic
      disorders with prenatal onset. Ultrasound criteria for differentiation from the
      most common type of CNS-congenital nephrosis of the Finnish type (CNF)-are
      discussed. Because of its prognostic relevance, we advocate molecular genetic
      testing of LAMB2 in any case of prenatally detected nephrotic syndrome with
      negative results of NPHS1 mutational screening, especially in the presence of the
      typical sonomorphologic findings of the kidneys and the development of
      oligohydramnios.

PMID- 16450352
TI  - The OEIS complex: two case reports that illustrate the spectrum of abnormalities
      and a review of the literature.
AB  - We present two cases of OEIS (omphalocele, exstrophy, imperforate anus, spinal
      defects) complex -MIM 258040 and a review of the literature. Case 1 was a 14-year
      old girl who presented at 30 weeks' gestation. An ultrasound examination showed
      an omphalocele and spina bifida; the bladder was not visualised. She went into
      spontaneous labour two weeks later and the baby died shortly after birth. A full
      post-mortem examination was refused, but the mother did agree to an external
      examination, skin biopsy for fibroblast culture, X rays and MR imaging. The MR
      imaging showed a pelvic kidney, a large omphalocele containing the other kidney,
      liver, bowel and a fluid filled structure thought to represent an exstrophy of
      the bladder (EB). Case 2 was a 30-year-old woman who had an ultrasound
      examination at 20 weeks' gestation; this showed an omphalocele, but the bladder
      was not visualised. The pregnancy was subsequently terminated and a post-mortem
      examination showed a low set umbilical cord associated with a small omphalocele;
      there was an imperforate anus; a blind ending rectum terminated in the
      omphalocele. We conclude that these two cases illustrate the variability of the
      OEIS complex.

PMID- 16450353
TI  - Relaxometry model of strong dipolar perturbers for balanced-SSFP: application to
      quantification of SPIO loaded cells.
AB  - Magnetic resonance microscopy using magnetically labeled cells is an emerging
      discipline offering the potential for non-destructive studies targeting numerous
      cellular events in medical research. The present work develops a technique to
      quantify superparamagnetic iron-oxide (SPIO) loaded cells using fully balanced
      steady state free precession (b-SSFP) imaging. An analytic model based on phase
      cancellation was derived for a single particle and extended to predict mono
      exponential decay versus echo time in the presence of multiple randomly
      distributed particles. Numerical models verified phase incoherence as the
      dominant contrast mechanism and evaluated the model using a full range of tissue
      decay rates, repetition times, and flip angles. Numerical simulations indicated a
      relaxation rate enhancement (DeltaR(2b)=0.412 gamma . LMD) proportional to LMD,
      the local magnetic dose (the additional sample magnetization due to the SPIO
      particles), a quantity related to the concentration of contrast agent. A phantom
      model of SPIO loaded cells showed excellent agreement with simulations,
      demonstrated comparable sensitivity to gradient echo DeltaR(*) (2) enhancements,
      and 14 times the sensitivity of spin echo DeltaR(2) measurements. We believe this
      model can be used to facilitate the generation of quantitative maps of targeted
      cell populations.

PMID- 16450354
TI  - Numerical equilibration of signal intensity and spatial resolution in time
      resolved continuously moving table imaging.
AB  - Time-resolved continuously moving table imaging techniques have been previously
      developed to observe a dynamically changing phenomenon over an extended field-of
      view. The acquisition involves differential k-space sampling and view sharing.
      Since the table is continuously moving during data acquisition, the k-space for
      any longitudinal position is sampled only sparsely for the first reconstruction
      timeframe and is progressively more fully sampled for subsequent frames.
      Consequently, the signal intensity increases and the lateral spatial resolution
      improves from frame to frame even for static materials, which can mask true
      dynamically changing phenomena. This work provides a description of this effect
      and a means for signal correction in the early reconstruction frames, thus
      permitting any residual variation in signal intensity to be primarily attributed
      to true dynamic processes. The method is tested experimentally on a static
      phantom and in a peripheral vascular study designed to observe the leading edge
      of the contrast bolus.

PMID- 16450355
TI  - Reliability and validity of the Beck depression inventory in patients with
      Parkinson's disease.
AB  - We evaluated the validity, reliability, and potential responsiveness of the Beck
      Depression Inventory (BDI) in patients with Parkinson's disease (PD). In part 1
      of the study, 92 patients with PD underwent a structured clinical interview for
      DSM major depression and based on this patients were considered depressed (PD-D)
      or nondepressed (PD-ND). Subsequently, patients filled in the BDI. In part 2, a
      postal survey consisting the BDI was performed in 185 PD patients and 112
      controls. Test-retest reliability was assessed in 60 PD patients. The factor
      analysis revealed a cognitive-affective and a somatic factor. Cronbachs alpha for
      the BDI was 0.88. Mean BDI indicated significant differences (P<0.001) between
      the PD and control group, between the PD-ND and PD-D group, and between PD-ND and
      control group. In part 1, the receiver operating characteristic curves showed
      that the area under the curve for the total BDI was 0.88. A cutoff was calculated
      for the BDI (14/15) that had the highest sum of sensitivity (0.71) and
      specificity (0.90). In part 2, the test-retest reliability for the BDI total
      score was 0.89 (intraclass correlation coefficient). The smallest real difference
      was 3.3 for the total BDI. The BDI is a valid, reliable, and potential responsive
      instrument to assess the severity of depression in PD. However, an adjusted
      cutoff is recommended.

PMID- 16450356
TI  - Three-way translocation involves MLL, MLLT3, and a novel cell cycle control gene,
      FLJ10374, in the pathogenesis of acute myeloid leukemia with
      t(9;11;19)(p22;q23;p13.3).
AB  - The MLL gene, at 11q23, undergoes chromosomal translocation with a large number
      of partner genes in both acute lymphoblastic and acute myeloid leukemia (AML). We
      report a novel t(9;11;19)(p22;q23;p13.3) disrupting MLL in an infant AML patient.
      The 5' end of MLL fused to chromosome 9 sequences on the der(11), whereas the 3'
      end was translocated to chromosome 19. We developed long-distance inverse
      polymerase chain reaction assays to investigate the localization of the
      breakpoints on der(11) and der(19). We found that intron 5 of MLL was fused to
      intron 5 of MLLT3 at the der(11) genomic breakpoint, resulting in a novel in
      frame MLL exon 5-MLLT3 exon 6 fusion transcript. On the der(19), a novel gene
      annotated as FLJ10374 was disrupted by the breakpoint. Using reverse
      transcription-polymerase chain reaction analysis, we showed that FLJ10374 is
      ubiquitously expressed in human cells. Transfection of the FLJ10374 protein in
      different cell lines revealed that it localized exclusively to the nucleus. In
      serum-starved NIH-3T3 cells, the expression of FLJ10374 decreased the rate of the
      G1-to-S transition of the cell cycle, whereas the suppression of FLJ10374 through
      short interfering RNA increased cell proliferation. These results indicate that
      FLJ10374 negatively regulates cell cycle progression and proliferation. Thus, a
      single chromosomal rearrangement resulting in formation of the MLL-MLLT3 fusion
      gene and haplo-insufficiency of FLJ10374 may have cooperated to promote
      leukemogenesis in AML with t(9;11;19).

PMID- 16450357
TI  - Molecular cytogenetic characterization of doxorubicin-resistant neuroblastoma
      cell lines: evidence that acquired multidrug resistance results from a unique
      large amplification of the 7q21 region.
AB  - Neuroblastoma is a heterogeneous neural crest-derived embryonic childhood
      neoplasm that is the second most common solid tumor found in children. Despite
      recent advances in combined therapy, the overall survival of patients with high
      stage disease has not improved in the last decades. Treatment failure is in part
      attributed to multidrug resistance. To address the mechanisms involved in the
      development of multidrug resistance, we have generated two doxorubicin-resistant
      neuroblastoma cell lines (IGRN-91R and LAN-1R). These cells were shown to
      overexpress the MDR1 gene coding for the P-glycoprotein and were resistant to
      other MDR1- and non-MDR1-substrate drugs. Indeed, the MDR1 inhibitor verapamil
      only partially restored sensitivity to drugs, confirming that P-glycoprotein
      mediated drug efflux was not responsible for 100% resistance. High-resolution and
      array-based comparative genomic hybridization analyses revealed the presence of
      an amplicon in the 7q21 region as the unique genomic alteration common to both
      doxorubicin-resistant cell lines. In addition to the MDR1 locus, this large
      amplified region is likely to harbor additional genes potentially involved in the
      development of drug resistance. This study represents the first molecular
      cytogenetic and genomic approach to identifying genomic regions involved in the
      multidrug-resistant phenotype of neuroblastoma. These results could lead to the
      identification of relevant target genes for the development of new therapeutic
      modalities.

PMID- 16450358
TI  - The effect of the levonorgestrel intrauterine system on uterine artery blood flow
      1 year after insertion.
AB  - OBJECTIVE: To assess whether the morphological alterations of the endometrium
      induced by the levonorgestrel intrauterine system affect the uterine artery
      vasculature. METHODS: Forty-eight premenopausal women attending our gynecology
      clinic because of menorrhagia were enrolled into the study. Clinical measures of
      menstrual bleeding, endometrial thickness and Doppler flow of the uterine artery
      (resistance (RI) and pulsatility (PI) indices) were evaluated before and 1 year
      after insertion of the levonorgestrel intrauterine system. Thirty-three (69%)
      women were available for re-evaluation at the end of the first year and the
      continuation rate was 76% (n = 25). A paired samples t-test and the Mann-Whitney
      U-test were used for comparison of values between groups. RESULTS: The mean age
      of the thirty-three patients was 44.3 +/- 7.6 years. Nine patients (27.3%) were
      amenorrheic and three patients were in menopause at the end of the year. After
      excluding the women in menopause, the increase in mean RI 1 year after insertion
      was statistically significant (0.86 +/- 0.07 vs. 0.81 +/- 0.08; P = 0.046), as
      was the decrease in uterine volume (736.9 +/- 276.9 mL vs. 972.75 +/- 465.71 mL;
      P = 0.029). The mean endometrial thickness decreased 1 year after insertion, but
      not significantly (4.6 +/- 1.6 mm vs. 6.6 +/- 3.5 mm; P = 0.07) and there was no
      statistically significant difference in mean PI between the groups (2.00 +/- 0.63
      and 2.03 +/- 0.64 pre- and post-insertion, respectively; P = 0.83). CONCLUSION:
      The increase in mean RI of the uterine artery and the decrease in uterine volume
      1 year after insertion of the levonorgestrel intrauterine system may be related
      to its progestational effect. This increase in RI may have a role in cessation of
      menstruation.

PMID- 16450359
TI  - Meckel-Gruber syndrome: sonography and pathology.
AB  - OBJECTIVE: To define a specific sonographic pattern for the appearance of the
      kidneys in fetuses affected by Meckel-Gruber syndrome (MGS). METHODS: This was a
      retrospective analysis of 30 cases, collected from five centers, with ultrasound
      features suggestive of MGS. Only fetuses with a confirmed diagnosis of MGS were
      finally included. Analysis included a detailed evaluation of the sonographic
      findings and comparison with pathological follow-up. RESULTS: Seventeen cases met
      the pathological criteria for a diagnosis of MGS and were included in the study.
      In all cases, a typical sonographic pattern was seen: the kidneys were enlarged
      (mean, + 4.8 SD) and showed unusual corticomedullary differentiation, occurring
      as early as the first trimester. In most cases, the medullary areas appeared
      excessively large and mottled due to the presence of multiple small cysts.
      CONCLUSIONS: The kidneys of fetuses with MGS are enlarged, cystic and have
      unusual corticomedullary differentiation. These features can be observed as early
      as the first and early second trimesters.

PMID- 16450360
TI  - Fetal clavicle length throughout gestation: a nomogram.
AB  - OBJECTIVE: To create a nomogram of fetal clavicle length (CL) throughout
      gestation. METHODS: Cross-sectional study of patients between 14 and 42 weeks'
      gestation. Inclusion criteria consisted of well-established dates (consistent
      with early ultrasound), singleton, non-anomalous fetuses, and intact amniotic
      membranes. Sonographic measurements included biparietal diameter (BPD), head
      circumference (HC), abdominal circumference (AC), femur length (FL), humerus
      length (HL) and sonographically estimated fetal weight (SEFW). For every case,
      the average of three separate measurements of the CL was used. The 5th, 50th and
      95th centiles were obtained by least squares regression. Pearson's correlation
      coefficient and associated P-values for the relationships between CL and other
      biometric measurements were calculated. The data were compared to a nomogram of
      the CL generated in 1985 from the measurement of 85 fetuses. RESULTS: A total of
      623 consecutive patients were studied. In all but three cases, CL was
      successfully measured. Mean maternal age was 27.7 +/- 6.2 years, median gravidity
      3 (range, 1-14) and median parity 1 (range, 0-9). Mean CL (mm) = -75.30 +
      32.70*ln(GA) and SD = -0.41 + 0.08328*GA, where ln represents the natural
      logarithm and GA the gestational age in weeks. Fetal CL correlated significantly
      and strongly with BPD, HC, AC, HL, FL and the logarithm of SEFW, with Pearson
      correlation values of 0.973, 0.977, 0.976, 0.979, 0.977 and 0.979, respectively
      (all P < 0.001). Measurements according to comparable 1985 data were consistently
      substantially below the present data (smaller CL for any given GA except below 17
      weeks' gestation). CONCLUSIONS: We propose a new nomogram of CL, which differs
      significantly from the previously published nomogram. We suggest that the present
      data reflect the use of high-resolution ultrasound technology and propose that
      these data, based on a large number of fetuses, replace the previous nomogram. We
      also suggest that the '1 mm = 1 week' rule of thumb should no longer be used,
      since it can be erroneous by as much as 6 weeks.

PMID- 16450361
TI  - Ultrasound diagnosis of fourth branchial arch sinus at 22 weeks' gestation.
AB  - Fourth branchial arch sinus is the rarest of the branchial cleft anomalies and
      its prenatal detection has not previously been reported in the English
      literature. We describe a case of fourth branchial arch sinus identified in a
      fetus during a routine ultrasound evaluation at 22 weeks' gestation. Survey of
      the fetal anatomy revealed a small 'nipple-like' structure on the neck, arising
      anteriorly to the sternocleidomastoid muscle, midway between the chin and the
      left shoulder. The structure persisted unchanged throughout the pregnancy. The
      prenatal diagnosis of fourth branchial arch sinus was confirmed at delivery at
      term.

PMID- 16450362
TI  - WHISCY: what information does surface conservation yield? Application to data
      driven docking.
AB  - Protein-protein interactions play a key role in biological processes. Identifying
      the interacting residues is a first step toward understanding these interactions
      at a structural level. In this study, the interface prediction program WHISCY is
      presented. It combines surface conservation and structural information to predict
      protein-protein interfaces. The accuracy of the predictions is more than three
      times higher than a random prediction. These predictions have been combined with
      another interface prediction program, ProMate [Neuvirth et al. J Mol Biol
      2004;338:181-199], resulting in an even more accurate predictor. The usefulness
      of the predictions was tested using the data-driven docking program HADDOCK
      [Dominguez et al. J Am Chem Soc 2003;125:1731-1737] in an unbound docking
      experiment, with the goal of generating as many near-native structures as
      possible. Unrefined rigid body docking solutions within 10 A ligand RMSD from the
      true structure were generated for 22 out of 25 docked complexes. For 18
      complexes, more than 100 of the 8000 generated models were correct. Our results
      demonstrates the potential of using interface predictions to drive protein
      protein docking.

PMID- 16450363
TI  - Evaluation of different biological data and computational classification methods
      for use in protein interaction prediction.
AB  - Protein-protein interactions play a key role in many biological systems. High
      throughput methods can directly detect the set of interacting proteins in yeast,
      but the results are often incomplete and exhibit high false-positive and false
      negative rates. Recently, many different research groups independently suggested
      using supervised learning methods to integrate direct and indirect biological
      data sources for the protein interaction prediction task. However, the data
      sources, approaches, and implementations varied. Furthermore, the protein
      interaction prediction task itself can be subdivided into prediction of (1)
      physical interaction, (2) co-complex relationship, and (3) pathway co-membership.
      To investigate systematically the utility of different data sources and the way
      the data is encoded as features for predicting each of these types of protein
      interactions, we assembled a large set of biological features and varied their
      encoding for use in each of the three prediction tasks. Six different classifiers
      were used to assess the accuracy in predicting interactions, Random Forest (RF),
      RF similarity-based k-Nearest-Neighbor, Naive Bayes, Decision Tree, Logistic
      Regression, and Support Vector Machine. For all classifiers, the three prediction
      tasks had different success rates, and co-complex prediction appears to be an
      easier task than the other two. Independently of prediction task, however, the RF
      classifier consistently ranked as one of the top two classifiers for all
      combinations of feature sets. Therefore, we used this classifier to study the
      importance of different biological datasets. First, we used the splitting
      function of the RF tree structure, the Gini index, to estimate feature
      importance. Second, we determined classification accuracy when only the top
      ranking features were used as an input in the classifier. We find that the
      importance of different features depends on the specific prediction task and the
      way they are encoded. Strikingly, gene expression is consistently the most
      important feature for all three prediction tasks, while the protein interactions
      identified using the yeast-2-hybrid system were not among the top-ranking
      features under any condition.

PMID- 16450364
TI  - Echoplanar diffusion tensor imaging of the lower leg musculature using eddy
      current nulled stimulated echo preparation.
AB  - A sequence for echoplanar diffusion tensor imaging of musculature was developed
      using a stimulated echo preparation. The strategy was optimized in order to
      obtain reliable diffusion tensor data in a short measuring time. Image distortion
      problems due to eddy currents arising from long-lasting diffusion sensitizing
      gradients could be overcome by insertion of additional gradient pulses in the TM
      interval of the stimulated echo preparation. In contrast to former approaches
      with similar intention, the proposed strategy does not influence the stimulated
      echo signal itself and does not lead to prolonged echo time as in the case of
      spin echo methods. Phantom measurements were performed to compare eddy current
      induced distortion effects in diffusion weighted images. The diffusion tensor in
      the musculature of the lower leg was investigated in four healthy subjects and
      maps of the trace and the three eigenvalues of the diffusion tensor, fractional
      anisotropy maps, and angle maps were calculated.

PMID- 16450365
TI  - Rapid high-resolution T(1) mapping by variable flip angles: accurate and precise
      measurements in the presence of radiofrequency field inhomogeneity.
AB  - Rapid 3D mapping of T(1) relaxation times is valuable in diverse clinical
      applications. Recently, the variable flip angle (VFA) spoiled gradient recalled
      echo approach was shown to be a practical alternative to conventional methods,
      providing better precision and speed. However, the method is known to be
      sensitive to transmit field (B(1) (+)) inhomogeneity and can result in
      significant systematic errors in T(1) estimates, especially at high field
      strengths. The main challenge is to improve the accuracy of the VFA approach
      without sacrificing speed. In this article, the VFA method was optimized for both
      accuracy and precision by considering the influence of imperfect transmit fields,
      noise bias, and selection of flip angles. An analytic solution was developed for
      systematic B(1) (+)-induced T(1) errors and allows simple correction of T(1)
      measurements acquired with any imaging parameters. A noise threshold was also
      identified and provided a guideline for avoiding T(1) biases. Finally, it was
      shown that three flip angles were the most efficient for maintaining accuracy and
      high precision over large ranges of T(1). A rapid B(1) (+) mapping sequence was
      employed in all phantom experiments and high-field in vivo brain scans.
      Experimental results confirmed the theory and validated the accuracy of the
      proposed method.

PMID- 16450366
TI  - Design and analysis of a practical 3D cones trajectory.
AB  - The 3D Cones k-space trajectory has many desirable properties for rapid and ultra
      short echo time magnetic resonance imaging. An algorithm is presented that
      generates the 3D Cones gradient waveforms given a desired field of view and
      resolution. The algorithm enables a favorable trade-off between increases in
      readout time and decreases in the total number of required readouts. The
      resulting trajectory is very signal-to-noise ratio (SNR) efficient and has
      excellent aliasing properties. A rapid high-resolution ultra-short echo time
      imaging sequence is used to compare the 3D Cones trajectory to 3D projection
      reconstruction (3DPR) sampling schemes. For equivalent scan times, the 3D Cones
      trajectory has better SNR performance and fewer aliasing artifacts as compared to
      the 3DPR trajectory.

PMID- 16450367
TI  - Quantitative myocardial infarction on delayed enhancement MRI. Part I: Animal
      validation of an automated feature analysis and combined thresholding infarct
      sizing algorithm.
AB  - PURPOSE: To develop a computer algorithm to measure myocardial infarct size in
      gadolinium-enhanced magnetic resonance (MR) imaging and to validate this method
      using a canine histopathological reference. MATERIALS AND METHODS: Delayed
      enhancement MR was performed in 11 dogs with myocardial infarction (MI)
      determined by triphenyltetrazolium chloride (TTC). Infarct size on in vivo and ex
      vivo images was measured by a computer algorithm based on automated feature
      analysis and combined thresholding (FACT). For comparison, infarct size by human
      manual contouring and simple intensity thresholding (based on two standard
      deviation [2SD] and full width at half maximum [FWHM]) were studied. RESULTS:
      Both in vivo and ex vivo MR infarct size measured by the FACT algorithm
      correlated well with TTC (R = 0.95-0.97) and showed no significant bias on Bland
      Altman analysis (P = not significant). Despite similar correlations (R = 0.91
      0.97), human manual contouring overestimated in vivo MR infarct size by 5.4% of
      the left ventricular (LV) area (equivalent to 55.1% of the MI area) vs. TTC (P <
      0.001). Infarct size measured by simple intensity thresholdings was less accurate
      than the proposed algorithm (P < 0.001 and P = 0.007). CONCLUSION: The FACT
      algorithm accurately measured MI size on delayed enhancement MR imaging in vivo
      and ex vivo. The FACT algorithm was also more accurate than human manual
      contouring and simple intensity thresholding approaches.

PMID- 16450368
TI  - Quantitative myocardial infarction on delayed enhancement MRI. Part II: Clinical
      application of an automated feature analysis and combined thresholding infarct
      sizing algorithm.
AB  - PURPOSE: To compare global and regional myocardial infarction (MI) measurements
      on clinical gadolinium-enhanced magnetic resonance (MR) images using human manual
      contouring and a computer algorithm previously validated by histopathology, and
      to study the degree to which visual assessment and human contouring of infarct
      extent agreed with the computer algorithm. MATERIALS AND METHODS: Infarct size in
      20 patients was measured by human manual contouring and with an automated feature
      analysis and combined thresholding (FACT) computer algorithm. Short-axis slices
      were divided into myocardial sectors for regional analysis. Extent of infarction
      was also graded visually by consensus of expert readers and compared to human and
      computer contouring. RESULTS: Despite good correlations (R = 0.93-0.95) between
      human contouring and the FACT algorithm, human contouring overestimated infarct
      size by 3.8% of the left ventricle (23.8% of the MI) area (P < 0.001). Human
      contouring also overestimated the circumferential extent, transmural extent, and
      extent of infarction within a sector by 7.1%, 18.2%, and 27.9%, respectively (all
      P < 0.001). Both consensus reading and human contouring overestimated infarct
      grades compared with the FACT algorithm (P = 0.002 and P < 0.001). CONCLUSION:
      Clinically relevant overestimation of MI can occur in visual interpretation and
      in human manual contouring, particularly with respect to extent of infarction on
      a regional basis.

PMID- 16450369
TI  - Pyramidal tract maturation after brain injury in newborns with heart disease.
AB  - OBJECTIVE: Our objective was to quantify white matter tract development in term
      newborns with congenital heart disease, a population at high risk for
      perioperative brain injury, using magnetic resonance imaging diffusion tensor
      tractography (DTT). METHODS: Twenty-five newborns with congenital heart disease
      were imaged before and after surgery, with a median of 2 weeks between serial
      magnetic resonance imaging examinations. DTT was performed to segment bilateral
      pyramidal tracts using semiautomated fiber tracking software, and manual region
      of interest measurements were taken for comparison. RESULTS: Significant
      maturational rates of increasing fractional anisotropy (median, 4.4% per week)
      and decreasing mean diffusivity (D(av)) (median, -2.0% per week) in the pyramidal
      tract were measured in infants without brain injury. Fractional anisotropy
      maturation rates were highest in newborns with normal scans, intermediate
      (median, 2.4% per week) in those with postoperative injury, and lowest (median,
      0.9% per week) in those with preoperative injury, indicating a significant trend
      across brain injury groups (p = 0.015). D(av) maturation rates did not differ
      across injury groups (p = 0.15). Manual region of interest measures showed
      greater variability in serial measurements, and no significant differences were
      identified between injury groups, suggesting that DTT may provide more sensitive
      measures. INTERPRETATION: DTT is feasible in term newborns and may help to
      characterize abnormal white matter tract development following acquired brain
      injury.

PMID- 16450370
TI  - UCHL-1 is not a Parkinson's disease susceptibility gene.
AB  - OBJECTIVE: The UCHL-1 gene is widely cited as a susceptibility factor for
      sporadic Parkinson's disease (PD). The strongest evidence comes from a meta
      analysis of small studies that reported the S18Y polymorphism as protective
      against PD, after pooling studies of white and Asian subjects. Here, we present
      data that challenge this association. METHODS: In a new large case-control study
      in white individuals (3,023 subjects), the S18Y variant was not protective
      against PD under any genetic model of inheritance. Similarly, a more powerful
      haplotype-tagging approach did not detect other associated variants. RESULTS:
      Finally, in an updated S18Y-PD meta-analysis (6,594 subjects), no significant
      association was observed under additive, recessive, or dominant models (odds
      ratio = 1.00 [95% confidence interval: 0.74-1.33]; odds ratio = 1.01 [95%
      confidence interval: 0.76-1.35]; and odds ratio = 0.96 [95% confidence interval:
      0.86-1.08], respectively), and a cumulative meta-analysis showed a trend toward a
      null effect. INTERPRETATION: Based on the current evidence, the UCHL-1 gene does
      not exhibit a protective effect in PD.

PMID- 16450372
TI  - T(1) measurement of (31)P metabolites at rest and during steady-state dynamic
      exercise using a clinical nuclear magnetic resonance scanner.
AB  - This article illustrates some problems and possible solutions to determine the
      apparent spin-lattice relaxation time (T(1)) of the muscular (31)P metabolites at
      rest and during dynamic steady-state exercise using a clinical 1.5 T NMR scanner
      and a surface coil. T(1) was first estimated on a phosphates solution (phantom)
      using four different acquisition protocols, all based on the multiple-point
      "progressive saturation" method, and by fitting each data set with two different
      mathematical models. Subsequently, two of the four protocols and both models were
      used to estimate T(1) both at rest and during exercise on the calf muscles of 10
      healthy volunteers. Experimental results obtained on the phantom showed that T(1)
      is greatly affected by the longest nominal explored repetition time (P<0.001) and
      by the mathematical model (P<0.001), ranging from 0.65+/-0.10 to 8.4+/-0.8 s. The
      two acquisition protocols applied on volunteers yielded significantly different
      T(1) (P<0.001), which were also rather different from the literature values for
      the same metabolites. Nevertheless, independently of the acquisition protocol
      and/or the fitting procedure, T(1) of all muscular phosphagens did not change
      statistically from rest to steady-state aerobic exercise.

PMID- 16450371
TI  - Nuclear targeting of a midregion PTHrP fragment is necessary for stimulating
      growth in breast cancer cells.
AB  - Parathyroid-hormone related protein (PTHrP) is the primary factor in humoral
      hypercalcemia of malignancy and is highly secreted by breast cancers. The pro
      hormone undergoes post-translational processing and cleavage to give rise to
      mature secretory peptides, one of which is midregion PTHrP (38-94/95/101)
      containing a nuclear localisation sequence (NLS) in amino acids (87-106). The
      current study investigates whether the NLS in midregion PTHrP is important in
      breast cancer growth. PTHrP-(67-101), a midregion PTHrP fragment containing NLS
      (87-101) significantly increased growth of MCF-7 and MDA-MB231 cells (126.3 and
      121.3% of control respectively in serum conditions), independent of PTHR1 whereas
      PTHrP-(67-86), which lacks the NLS did not. Fluorescent-labelled PTHrP-(67-101)
      translocated to the nucleus, whereas PTHrP-(67-86) remained cytosolic and a
      scrambled(+NLS) peptide was not internalised. In comparison, no growth influence
      or uptake was seen in non-tumour breast cells (Hs578Bst). Increases in
      intracellular calcium mobilisation were observed in breast cancer cells
      stimulated with both PTHrP-(67-101) and PTHrP-(67-86) (EC(50) of 3.2 pM and 2.2
      pM respectively for MCF-7 cells), whereas inositide turnover was not detected.
      Both nuclear uptake and calcium signalling were attenuated in the presence of
      EGTA, but not with U73122 or N-terminal PTHrP peptides. Our studies indicate that
      the NLS-containing midregion PTHrP peptide is dependent on both internalisation
      and nuclear translocation to induce growth in breast cancer cells. These findings
      highlight the importance of midregion PTHrP and its receptor in breast cancer
      growth and may provide potential targets for future therapeutic intervention.

PMID- 16450373
TI  - Cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in patients with
      melanoma: a potential marker of response to immunotherapy?
AB  - Simple, noninvasive methods are needed to follow effectiveness of new treatments
      in patients with melanoma. In our study, we examined cytoplasmic melanoma
      associated antigen (CYT-MAA) serum level in melanoma patients during
      immunotherapy. Sera of 117 patients were assayed for CYT-MAA by double-sandwich
      ELISA before and during treatment with a polyvalent, shed antigen, melanoma
      vaccine. Vaccine-treated patients included 30 with American Joint Committee on
      Cancer (AJCC) stage IIb or IIIa, 30 with stage IIc, IIIb or IIIc, 30 with
      resected stage IV and 27 with measurable stage IV disease. Prior to vaccine
      therapy, 63% of patients had elevated serum CYT-MAA with high levels of antigen
      in all disease stages. After initiation of therapy, the level declined in more
      than 90% of the positive patients and fell below the positive cut-off in 56% of
      these patients within 5 months. By contrast, there was no decline in CYT-MAA
      serum level in 11 patients who served as untreated controls with melanoma.
      Multivariate analysis of the treated patients using accelerated failure time
      Weibull models adjusted for stage and age showed that patients whose CYT-MAA
      serum level remained elevated during treatment were approximately 3 times more
      likely to recur or progress than patients who were consistently below the
      positive cut-off (hazard ratio = 3.42, 95% CI [1.38, 8.47], p = 0.0079).
      Measurement of CYT-MAA serum level appears to show potential as an early marker
      of prognosis in patients with stages IIb to IV melanoma. Measurement of CYT-MAA
      serum level during therapy could provide an intermediate marker of response in
      these patients.

PMID- 16450374
TI  - High antineoplastic activity of new heterocyclic compounds in cancer cells with
      resistance against classical DNA topoisomerase II-targeting drugs.
AB  - Twenty previously synthesized fused heterocyclic DNA-topoisomerase II (Topo II)
      inhibiting compounds were investigated for their potential efficacy in various
      human cancer cell lines that were derived from different tumor entities.
      Moreover, different multidrug-resistant variants of these cancer cell lines with
      decreased Topo II expression were investigated. In parental, drug-sensitive cells
      merely the compounds BD3 and G35 showed efficacies, in terms of microM, which
      were similar to that of the classical Topo II inhibitor etoposide. On the other
      hand, most of the tested heterocyclic compounds were found more effective in drug
      resistant cells than in the parental, drug-sensitive ones, and some of the
      compounds showed high antineoplastic efficacy in several drug-resistant cell
      models. Compounds BD13, BD14 and BD16 exhibited high antineoplastic activities
      against the drug-resistant sublines EPG85-257RNOV and EPG85-257RDB derived from
      gastric carcinoma, EPP85-181RNOV and EPP85-181RDB derived from pancreatic
      carcinoma, MCF-7/Adr derived from breast cancer, D79/86RNOV derived from
      fibrosarcoma, and MeWoETO1 derived from melanoma. Furthermore, compound D23 was
      found highly efficient in the multidrug-resistant variants HT-29RNOV and HT-29RDB
      derived from colon carcinoma, and compound D24 exhibited the highest
      antineoplastic activity among the tested compounds in the drug-resistant subline
      MDA-MB-231ROV derived from breast cancer. In conclusion, compounds BD 13, BD 14,
      BD 16, D 23 and D 24 may be useful for the treatment of different multidrug
      resistant cancer cells with cross resistance against "classical" Topo II
      targeting drugs.

PMID- 16450375
TI  - Navigator gated high temporal resolution tissue phase mapping of myocardial
      motion.
AB  - Data acquisition for phase contrast velocity mapping of myocardial motion is
      typically based on multiple breath-held 2D measurements with limited acquisition
      duration and consequently relatively poor temporal resolution. In order to
      overcome the limitations of breath-hold acquisitions, an improved navigator
      guided technique was implemented based on 2 navigator signals within each cardiac
      cycle in combination with paired acceptance and rejection criteria of successive
      navigator signals. Respiratory gated phase contrast measurements with 3
      directional velocity encoding were performed in 12 healthy volunteers in basal,
      midventricular, and apical locations of the left ventricle during free breathing
      with a temporal resolution of 13.8 ms. Results were compared to standard breath
      hold measurements with a temporal resolution of 69 ms. Data from the high
      temporal resolution study revealed details in left ventricular motion patterns
      that were previously not seen in phase contrast measurements and are only known
      from echocardiography. The proposed navigator gated technique for high temporal
      resolution velocity mapping is, therefore, highly promising for the detection of
      local and global motion abnormalities in patients with disturbed left ventricular
      performance, such as diastolic dysfunction.

PMID- 16450377
TI  - Telomere DNA content and allelic imbalance demonstrate field cancerization in
      histologically normal tissue adjacent to breast tumors.
AB  - Cancer arises from an accumulation of mutations that promote the selection of
      cells with progressively malignant phenotypes. Previous studies have shown that
      genomic instability, a hallmark of cancer cells, is a driving force in this
      process. In the present study, two markers of genomic instability, telomere DNA
      content and allelic imbalance, were examined in two independent cohorts of
      mammary carcinomas. Altered telomeres and unbalanced allelic loci were present in
      both tumors and surrounding histologically normal tissues at distances at least 1
      cm from the visible tumor margins. Although the extent of these genetic changes
      decreases as a function of the distance from the visible tumor margin, unbalanced
      loci are conserved between the surrounding tissues and the tumors, implying
      cellular clonal evolution. Our results are in agreement with the concepts of
      "field cancerization" and "cancer field effect," concepts that were previously
      introduced to describe areas within tissues consisting of histologically normal,
      yet genetically aberrant, cells that represent fertile grounds for tumorigenesis.
      The finding that genomic instability occurs in fields of histologically normal
      tissues surrounding the tumor is of clinical importance, as it has implications
      for the definition of appropriate tumor margins and the assessment of recurrence
      risk factors in the context of breast-sparing surgery.

PMID- 16450376
TI  - MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over
      expressing ErbB2.
AB  - Ethanol is a tumor promoter and may enhance the metastasis of breast cancer. We
      have previously demonstrated that over-expression of ErbB2 promoted ethanol
      mediated invasion of mammary epithelial cells and breast cancer cells. However,
      the underlying cellular/molecular mechanisms remain unknown. By gelatin
      zymography, we showed that over-expression of ErbB2 increased the production of
      matrix metalloproteinase-2 (MMP-2) and MMP-9 in human mammary epithelial cells
      (HB2). Transient or stable transfection of ErbB2 cDNA to HB2 cells upregulated
      the transcripts and the activity of the MMP-2/-9 gene promoter; the upregulation
      of MMP-2/-9 expression was mediated by p38 mitogen-activated protein kinase (p38
      MAPK) and phosphatidylinositol 3-kinase (PI3K). Although ethanol, at
      physiologically relevant concentrations (100-400 mg/dl), did not affect the
      production of MMP-2/-9, it activated MMP-2 in HB2 cells over-expressing ErbB2
      (HB2(ErbB2)), but not HB2 cells; it enhanced the cleavage of proform MMP-2 (72
      kDa) to an active form (62 kDa). The activation was dependent on c-jun N-terminal
      kinases (JNKs) and reactive oxygen species (ROS). On the other hand, ethanol
      affected neither the expression nor the activation of MMP-9. Selective inhibitors
      of MMP-2 (SB-3CT and OA-Hy) and antioxidants significantly inhibited ethanol
      stimulated invasion of HB2(ErbB2) cells. Furthermore, knocking down MMP-2 by
      small interference RNA also induced a partial blockage on ethanol-promoted
      invasion of HB2(ErbB2) cells. Thus, ethanol-stimulated invasion of cells over
      expressing ErbB2 was mediated, at least partially, by MMP-2 activation.

PMID- 16450378
TI  - Plasma levels of receptor activator of nuclear factor-kappaB ligand and
      osteoprotegerin in patients with neuroblastoma.
AB  - Earlier reports showed that the balance between receptor activator of nuclear
      factor-kappaB ligand (RANKL) and its decoy-receptor osteoprotegerin (OPG) plays
      an important role in the pathogenesis of metastatic osteolysis induced by
      neuroblastoma cells. In this study, we investigated whether circulating levels of
      OPG, RANKL and their ratio were associated to the presence of osteolytic lesions
      in advanced neuroblastoma, as well as whether they provided additional
      information on the severity and prognosis of the disease. Plasma levels of RANKL
      and OPG were measured in 54 newly diagnosed neuroblastomas; 27 of them showed
      metastatic disease (stage IV), including 19 bone dissemination. Thirty-five
      children who were admitted to the pediatric department for minor surgical
      problems served as control group. OPG was significantly lower in all patients
      compared with controls, while RANKL levels were significantly increased in
      advanced neuroblastoma. OPG-to-RANKL ratio decreased in stage-IV patients, and
      particularly in those who had bone metastases. The diagnostic accuracy of the OPG
      to-RANKL ratio in discriminating the presence of osteolytic lesions was not
      confirmed statistically. OPG correlated significantly with other prognostic
      factors, namely, ferritin and neurone-specific enolase. In addition, an inverse
      relationship was found between OPG and event-free survival, and it was more
      significant in patients who had bone metastasis. This pilot study confirms that
      the production of OPG and RANKL is disregulated in neuroblastoma. Although the
      OPG-to-RANKL ratio does not have a predictive value in detecting bone metastasis,
      the measurement of the previously mentioned markers could be useful in decisions
      regarding the use of adjuvant therapies.

PMID- 16450379
TI  - Particulate endocytosis mediates biological responses of human mesenchymal stem
      cells to titanium wear debris.
AB  - Continual loading and articulation cycles undergone by metallic (e.g., titanium)
      alloy arthroplasty prostheses lead to liberation of a large number of metallic
      debris particulates, which have long been implicated as a primary cause of
      periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long
      term stability of total joint replacement prostheses relies on proper integration
      between implant biomaterial and osseous tissue, and factors that interfere with
      this integration are likely to cause osteolysis. Because multipotent mesenchymal
      stem cells (MSCs) located adjacent to the implant have an osteoprogenitor
      function and are critical contributors to osseous tissue integrity, when their
      functions or activities are compromised, osteolysis will most likely occur. To
      date, it is not certain or sufficiently confirmed whether MSCs endocytose
      titanium particles, and if so, whether particulate endocytosis has any effect on
      cellular responses to wear debris. This study seeks to clarify the phenomenon of
      titanium endocytosis by human MSCs (hMSCs), and investigates the influence of
      endocytosis on their activities. hMSCs incubated with commercially pure titanium
      particles exhibited internalized particles, as observed by scanning electron
      microscopy and confocal laser scanning microscopy, with time-dependent reduction
      in the number of extracellular particles. Particulate endocytosis was associated
      with reduced rates of cellular proliferation and cell-substrate adhesion,
      suppressed osteogenic differentiation, and increased rate of apoptosis. These
      cellular effects of exposure to titanium particles were reduced when endocytosis
      was inhibited by treatment with cytochalasin D, and no significant effect was
      seen when hMSCs were treated only with conditioned medium obtained from
      particulate-treated cells. These findings strongly suggest that the biological
      responses of hMSCs to wear debris are triggered primarily by the direct
      endocytosis of titanium particulates, and not mediated by secreted soluble
      factors. In this manner, therapeutical approaches that suppress particle
      endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance
      long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic
      osteolysis.

PMID- 16450380
TI  - Generation of tumoricidal PAX3 peptide antigen specific cytotoxic T lymphocytes.
AB  - The transcription factor PAX3 is expressed during early embryogenesis and in
      multiple cancer types, including embryonal rhabdomyosarcoma (ERMS), Ewing sarcoma
      (ES) and malignant melanoma (MEL), suggesting that it could function as a general
      tumor associated antigen. Major histocompatibility complex (MHC) peptide binding
      algorithms were used to predict potential epitopes in PAX3 capable of stimulating
      in vitro naive HLA-A0201 restricted cytotoxic T-lymphocytes (CTLs). Two peptides,
      PAX3-282 (QLMAFNHLI) and a modified version of this peptide PAX3-282.9V
      (QLMAFNHLV), were capable of inducing antigen-specific CTLs. Of these peptides,
      PAX3-282.9V was the most efficient inducer of primary CTL response. These CTLs
      were able to lyse HLA-A0201 expressing target cells that were pulsed with
      peptide, and more importantly, were effective in killing tumor cells that express
      PAX3, including ERMS, ES and MEL cell lines. These findings provide compelling
      evidence that peptide PAX3-282 is naturally processed by tumors and is presented
      in the context of HLA-A0201 in adequate amounts to allow CTL recognition. Also,
      PAX3-282.9V is an effective immunogenic peptide able to induce CTL recognition of
      PAX3-containing tumors and may be used as an antitumor peptide vaccine.

PMID- 16450381
TI  - Suppression of cortical spreading depression in migraine prophylaxis.
AB  - OBJECTIVE: Topiramate, valproate, propranolol, amitriptyline, and methysergide
      have been widely prescribed for migraine prophylaxis, but their mechanism or site
      of action is uncertain. Cortical spreading depression (CSD) has been implicated
      in migraine and as a headache trigger and can be evoked in experimental animals
      by electrical or chemical stimulation. We hypothesized that migraine prophylactic
      agents suppress CSD as a common mechanism of action. METHODS: Rats were treated
      either acutely or chronically over weeks and months, with one of the above
      migraine prophylactic drugs, vehicle, or D-propranolol, a clinically ineffective
      drug. The impact of treatment was determined on the frequency of evoked CSDs
      after topical potassium application or on the incremental cathodal stimulation
      threshold to evoke CSD. RESULTS: Chronic daily administration of migraine
      prophylactic drugs dose-dependently suppressed CSD frequency by 40 to 80% and
      increased the cathodal stimulation threshold, whereas acute treatment was
      ineffective. Longer treatment durations produced stronger CSD suppression.
      Chronic D-propranolol treatment did not differ from saline control.
      INTERPRETATION: Our data suggest that CSD provides a common therapeutic target
      for widely prescribed migraine prophylactic drugs. Assessing CSD threshold may
      prove useful for developing new prophylactic drugs and improving upon existing
      ones.

PMID- 16450382
TI  - Detecting white matter injury in sickle cell disease using voxel-based
      morphometry.
AB  - OBJECTIVE: Sickle cell disease (SCD) is associated with cerebrovascular disease,
      cerebral infarction, and cognitive dysfunction. This study aimed to detect the
      presence and extent of white matter abnormalities in individuals with SCD using
      voxel-based morphometry (VBM). METHODS: Thirty-six children and adolescents with
      SCD (age range, 9-24 years) and 31 controls (8-25 years) underwent magnetic
      resonance investigations using T1- and T2-weighted protocols. White and gray
      matter density maps were obtained from three-dimensional magnetic resonance
      imaging (MRI) data sets. Using VBM, we compared the maps between controls and SCD
      individuals with silent white matter infarct lesions (SCD+L; n = 16), and those
      without visible abnormality (SCD-L; n = 20). RESULTS: In comparison with
      controls, intelligence quotients (IQs) were lower in both SCD groups irrespective
      of presence of visible lesions. VBM showed widespread bilateral white matter
      abnormalities in the SCD+L group, extending beyond the regions of focal
      infarction in the deep anterior and posterior white matter borderzones. Bilateral
      white matter abnormalities were also observed in the SCD-L group, in locations
      similar to those in the SCD+L group. INTERPRETATION: VBM is sensitive to
      detection of widespread white matter injury in SCD patients in borderzones
      between arterial territories even in the absence of evidence of infarction. Those
      changes may contribute to cognitive deficits in this population.

PMID- 16450383
TI  - Truncated APC is required for cell proliferation and DNA replication.
AB  - The tumour suppressor APC is truncated in most colon cancers, which leads to the
      stabilization of beta-catenin and to the constitutive activation of Wnt
      signalling. However, it is not clear why colon cancer cells retain the truncated
      APC fragment. Here, we show that a decrease of APC levels achieved by RNA
      interference impairs cell proliferation and DNA replication, not only in 293
      cells that express a wild-type protein, but also in SW480 colon cancer cells that
      express exclusively a truncated APC fragment. This correlates with a reduction of
      the levels of cyclin A, cyclin A-dependent kinase activity, p27(kip1) and the
      catalytic subunit of DNA polymerase delta. Thus, our data suggest that colon
      cancer cells retain a truncated APC fragment because it is essential for cell
      proliferation.

PMID- 16450384
TI  - Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel
      induced cancer cell death both in vitro and in vivo.
AB  - Intracellular events following paclitaxel binding to microtubules that lead to
      cell death remain poorly understood. Because reactive oxygen species (ROS) are
      involved in the cytotoxicity of anticancer agents acting through independent
      molecular targets, we explored the role of ROS in paclitaxel cytotoxicity. Within
      15 min after in vitro exposure of A549 human lung cancer cells to paclitaxel, a
      concentration-dependent intracellular increase in O(o)(2)(-) and H(2)O(2) levels
      was detected by spectrofluorometry. Addition of N-acetylcysteine (NAC) or
      glutathione, two H(2)O(2) scavenger, induced a 4-fold increase in paclitaxel
      IC(50). Delaying NAC co-incubation by 4 hr, resulted in a 3-fold reduction in
      cell protection. The glutathione synthesis inhibitor, buthionine sulfoximine
      significantly increased paclitaxel cytotoxicity and H(2)O(2) accumulation, but
      did not modify O(o)(2)(-) levels. Co-incubation with diphenylene iodonium
      suggested that paclitaxel induced-O(o)(2)(-) production was in part associated
      with increased activity of cytoplasmic NADPH oxidase. Concomitant treatment with
      inhibitors of caspases 3 and 8 increased cell survival but did not prevent the
      early accumulation of H(2)O(2.) To evaluate the role of ROS in paclitaxel
      antitumoral activity, mice were injected with LLC1 lung cancer cells and treated
      with paclitaxel i.p. and/or NAC. The antitumoral activity of paclitaxel in mice
      was abolished by NAC. In conclusion, the accumulation of H(2)O(2) is an early and
      crucial step for paclitaxel-induced cancer cell death before the commitment of
      the cells into apoptosis. These results suggest that ROS participate in vitro and
      in vivo to paclitaxel cytotoxicity.

PMID- 16450385
TI  - Evolution of cerebral arteriopathies in childhood arterial ischemic stroke.
AB  - OBJECTIVE: To investigate evolution of cerebral arteriopathy in children with
      arterial ischemic stroke (AIS) and its influence on recurrence. METHODS:
      Arteriopathy severity was graded on serial magnetic resonance angiograms from 50
      children with first AIS; diagnostic categories were assigned. RESULTS:
      Arteriopathy affected 72 arteries in 43 of 50 children. Five had clinical
      recurrence, with reinfarction in four; another had clinically silent
      reinfarction. Twelve children (24%; 4 with recurrence) had progressive
      arteriopathy. Arteriopathy improved in 24 patients (including 1 with recurrent
      transient ischemic attacks) and was stable in 7 patients. Magnetic resonance
      angiograms remained normal in seven patients; one had recurrent stroke. Diagnoses
      were transient cerebral arteriopathy (n = 24), chronic cerebral arteriopathy (n =
      11), arterial dissection (n = 3), possible moyamoya (n = 2), primary moyamoya (n
      = 1), dysplastic arteriopathy (n = 1), and cerebral vasculitis (n = 1). Some of
      the first two categories could represent thromboembolic arterial occlusion with
      recanalization. The hazard of recurrence was three times higher when arterial
      disease had progressed (Cox regression hazard ratio, 3.2; 95% confidence
      intervals, 0.5-20.3; p = 0.22). After adjustment for age and number of AIS risk
      factors, the hazard ratio was 3.1 (95% confidence interval, 0.4-22.2; p = 0.27).
      INTERPRETATION: Arteriopathy frequently progresses after childhood AIS. Further
      studies are needed to examine the relationship between progressive arteriopathy
      and recurrence.

PMID- 16450386
TI  - VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and
      gene deletion in endothelial cells.
AB  - The ability to target gene deletion to a specific cellular compartment via the
      Cre/loxP system has been a powerful tool in the analysis of broadly expressed
      genes. Here, we report the generation of a transgenic mouse line in which
      expression of Cre-recombinase is under the regulatory control of the VE-Cadherin
      promoter. Temporal distribution and activity of the enzyme was evaluated with two
      independent Cre reporter lines. Histological analysis was performed throughout
      development and in the adult. Recombination of lox P sites with subsequent
      expression of beta-galactosidase or GFP was detected as early as E7.5 in
      endothelial cells of the yolk sac. Progressive staining of the embryonic
      vasculature was noted from E8.5-13.5; however, more contiguous reporter
      expression was only seen by E14.5 onward in all endothelial compartments
      including arteries, veins, and capillaries. In addition, we found Cre activity in
      lymphatic endothelial cells. Unlike other endothelial-specific Cre mice, this
      model showed expression in the adult quiescent vasculature. Furthermore, the
      constitutive nature of the VE-Cadherin promoter in the adult can be advantageous
      for analysis of gene deletion in pathological settings.

PMID- 16450387
TI  - G3139 antisense oligonucleotide directed against antiapoptotic Bcl-2 enhances
      doxorubicin cytotoxicity in the FU-SY-1 synovial sarcoma cell line.
AB  - Synovial sarcoma (SS) is a highly aggressive, periarticular soft tissue sarcoma
      that causes death in more than half of affected children, adolescents, and young
      adults. Five- and 10-year survival rates are as low as 36 and 20%, respectively.
      Bcl-2, a negative regulator of apoptosis, is overexpressed in up to 90% of SS.
      Increased Bcl-2 expression not only leads to the development of cancer, but also
      to resistance of many anticancer chemotherapeutic agents. We hypothesized
      reducing Bcl-2 expression in SS should enhance doxorubicin cytotoxicity. Cell
      cultures representing two human sarcomas (FU-SY-1 SS and the pleomorphic SW982)
      and a primary human dermal fibroblast comparator (NHDF) were exposed in vitro to
      doxorubicin, or to doxorubicin preceded by Bcl-2 (G3139) antisense
      oligonucleotides, and assayed for cell survival, apoptosis, and modulations in
      Bcl-2 and Bcl-xL mRNA and protein content. SW982 sarcoma cells proved most
      susceptible to doxorubicin, while NHDF mesenchymal cells were least sensitive to
      doxorubicin. Treatment of FU-SY-1 SS with G3139 reduced Bcl-2 mRNA and protein
      levels, which enhanced doxorubicin-induced cell killing. There was a concurrent
      reduction in Bcl-xL mRNA following G3139 application in FU-SY-1 and NHDF
      cultures, but not in SW982. G3139 anti-Bcl-2 intervention sensitized the FU-SY-1
      SS to doxorubicin, due to increased apoptosis. G3139 intervention was ineffective
      in the two non-SS cell lines.

PMID- 16450388
TI  - Performance of clinical mammography: a nationwide study from Denmark.
AB  - Clinical mammography is the key tool for breast cancer diagnosis, but little is
      known about the impact of the organisational set-up on the performance. We
      evaluated whether organisational factors influence the performance of clinical
      mammography. Clinical mammography data from all clinics in Denmark in the year
      2000 were collected and linked to cancer outcome. Use of the National Institute
      of Radiation Hygiene register for identification of radiology clinics ensured
      comprehensive nationwide registration. We used the final mammographic assessment
      at the end of the imaging work-up to determine sensitivity, specificity and
      accuracy, the latter using a receiver-operating characteristics (ROC) analysis.
      In 96,534 clinical mammography examinations, sensitivity was 75% and specificity
      99%. The presence of at least one high volume-reading radiologist in the clinic
      increased accuracy (AUC = 0.91 for <1,000 examinations/year and 0.92 for >2,000
      examinations/year, p = 0.017). The examination volume per clinic showed no clear
      effect on performance, as accuracy was significantly higher in clinics with a
      medium number of examinations (AUC = 0.93 for 2,000-4,000 examinations/year and
      0.90 for >6,000 examinations/year, p = 0.003). Accuracy was significantly lower
      in regions with high annual utilisation rate of clinical mammography, which means
      the proportion of examined women in a region (AUC = 0.90 for 3.0-5.0% annual
      utilisation rate and AUC = 0.93 for 2.0-2.5% annual utilisation rate, and p =
      0.001), indicating that clinical mammography worked best in patient populations
      of purely symptomatic women. Our data indicate that to increase the accuracy of
      clinical mammography at the community level, the presence of an experienced
      radiologist should be prioritized ahead of raising the clinic size.

PMID- 16450389
TI  - SAHA-sensitized prostate cancer cells to TNFalpha-related apoptosis-inducing
      ligand (TRAIL): mechanisms leading to synergistic apoptosis.
AB  - Treatment of cancer cells with histone deacetylase inhibitors (HDACi) such as
      suberolylanilide hydroxamic acid (SAHA) activates genes that promote apoptosis.
      To enhance proapoptotic efficiency, SAHA has been used in combination with
      radiation, kinase inhibitors and cytotoxic drugs. Although several prostate cells
      respond to TNFalpha-Related Apoptosis-Inducing Ligand (TRAIL), LNCaP are
      resistant. This model system was utilized to examine the advantages of combined
      treatment with SAHA and TRAIL. In LNCaP cells, TRAIL induced synergistic
      apoptosis when combined even with the lowest dose of SAHA. Treatment with caspase
      inhibitor confirmed that SAHA-induced apoptosis was mediated through caspases. In
      addition to induction of apoptosis, SAHA and TRAIL decreased the levels of
      proapoptotic proteins IKKalpha, IKKbeta and IKKgamma, suggesting that SAHA
      treatment may reduce the activity of NFkappaB. However, assay for NFkappaB
      luciferase reporter activity showed highly significant increase in SAHA-treated
      cells, supporting earlier suggestions that HDACi promotes NFkappaB
      transcriptional activity. Further analyses to determine the mechanisms by which
      the combination of SAHA and TRAIL led to synergistic apoptosis indicated that the
      apoptotic response of LNCaP is due to a complex regulation of death receptor
      pathway and alterations of NFkappaB activity at several regulatory steps.

PMID- 16450390
TI  - Statins revert doxorubicin resistance via nitric oxide in malignant mesothelioma.
AB  - Human malignant mesothelioma (HMM) is resistant to many anticancer drugs,
      including doxorubicin. Mevastatin and simvastatin, 2 inhibitors of 3-hydroxy-3
      methylglutaryl coenzyme A (HMGCoA) reductase, potentiated the intracellular
      accumulation and the cytotoxicity of doxorubicin in HMM cells constitutively
      expressing P-glycoprotein and multidrug resistance-associated protein 3. This
      effect of statins was nitric oxide (NO)-dependent, since it was reverted by
      either an NO synthase inhibitor or an NO scavenging system. The NO synthase up
      regulation in HMM and other cells is known to be associated with the activation
      of the transcription factor NF-kappaB: in HMM cells statins increased the NF
      kappaB translocation into the nucleus, decreased the level of the NF-kappaB
      inhibitor IkBalpha and increased the phosphorylation/activation of IkB kinase
      alpha (IKKalpha). IKKalpha is under the negative control exerted by RhoA in its
      prenylated (active) form: incubation of HMM cells with statins lowered the amount
      of active RhoA and the level of Rho-associated kinase activity. All statins'
      effects were reverted by mevalonic acid, thus suggesting that they were mediated
      by the inhibition of HMGCoA reductase and were likely to be subsequent to the
      reduced availability of precursor molecules for RhoA prenylation. Both the Rho
      kinase inhibitor Y27632 and the RhoA inhibitor toxin B (from Clostridium
      difficile) mimicked the statins' effects, enhancing doxorubicin accumulation, NO
      synthesis and IKKalpha phosphorylation and decreasing the amount of IkBalpha in
      HMM cells. Simvastatin, Y27632 and toxin B elicited tyrosine nitration in the P
      glycoprotein, thus providing a likely mechanism by which NO reverts the
      doxorubicin resistance in HMM cells.

PMID- 16450391
TI  - Is there a folate-related gene-environment interaction in the etiology of
      childhood acute lymphoblastic leukemia?
AB  - Acute lymphoblastic leukaemia (ALL) is the commonest childhood cancer in
      developed countries. Little is known about its causes, although its early age at
      diagnosis has focused interest on maternal and perinatal factors. We have
      previously observed a protective effect of maternal folate supplementation during
      pregnancy against ALL, and a number of studies have reported protective effects
      of some common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR)
      gene. One study has suggested that the effect of MTHFR polymorphisms on risk of
      ALL may depend on folate status. This study aimed to look for evidence of an
      interaction between maternal folate supplementation and child's genotype among
      the cases from our previous study. Bone marrow specimens from 82 of 83 case
      children were available. DNA was extracted and genotyped for MTHFR C677T and
      A1298C using standard techniques. We used a case-only analysis to estimate the
      case-only odds ratio (COR) for MTHFR genotype and folate supplementation in
      association with ALL. None of the CORs indicated a significant departure from a
      multiplicative model. Adjustment for sex, age or genotype at the other locus had
      little effect on the results. Other studies of this gene and environment
      interaction in ALL and other cancers have produced contradictory results, perhaps
      because of varying definitions of folate exposure. Further research into the
      interaction of folate intake and genotype in causing ALL and other cancers is
      needed. We are specifically studying it in an Australian national case-control
      study of genetic and environmental causes of ALL.

PMID- 16450393
TI  - Sialyltransferase STX (ST8SiaII): a novel molecular marker of metastatic
      neuroblastoma.
AB  - Polysialic acid (PSA) is highly expressed in many human cancers, including
      neuroblastoma (NB), and is critical for cellular adhesion, neuronal migration and
      tumor metastasis. The key enzyme responsible for PSA synthesis is
      sialyltransferase STX (ST8SiaII). Using quantitative RT-PCR we (i) studied STX
      expression in 39 NB tumors and 8 cell lines and (ii) examined its potential
      clinical utility as an early response marker in the bone marrows of the entire
      cohort of 136 high-risk NB patients treated with an immunotherapy protocol
      utilizing anti-GD2 antibody 3F8 and GM-CSF. Based on the quantitation of 24
      normal marrow and peripheral blood samples, a normalized STX transcript value
      below the mean + 2SD was defined as negative. Sensitivity of this assay was 1 NB
      cell in 10(6) normal mononuclear cells. STX expression was high among NB tumors
      of all stages, as well as NB cell lines of different phenotypes. Evaluation for
      early (2.5 months from protocol entry) marrow response by univariate Cox model
      indicated that STX marker status (positive versus negative) was strongly
      associated with both progression-free and overall survival (p < 0.0005 for both).
      Similarly, the STX transcript level of posttreatment marrows was also highly
      prognostic of outcome (PFS, p = 0.001; OS, p < 0.0005). We conclude that STX mRNA
      has potential clinical utility as a molecular marker of metastatic NB.

PMID- 16450394
TI  - Optical diagnosis of cervical cancer by fluorescence spectroscopy technique.
AB  - In the present work, we examine normal and malignant stage IIIB cervical tissue
      by laser induced fluorescence, with 2 different objectives. (i) Development of
      the fluorescence spectroscopy technique as a standard optical method for
      discrimination of normal and malignant tissue samples and, (ii) Optimization of
      the technique by the method of matching of a sample spectrum with calibration
      sets of spectra of pathologically certified samples. Laser-induced fluorescence
      spectra were measured using samples from 62 subjects at different excitation
      wavelengths. Principal component analysis (PCA) of spectra and intensity ratios
      of curve-resolved fluorescence peaks were tested for discrimination. It was found
      that PCA of total fluorescence at 325 nm excitation gives specificity and
      sensitivity over 95%. Use of calibration sets of spectra of histo-pathologically
      certified samples combined with PCA for matching and pass/fail classification of
      test samples is shown to have high sensitivity/specificity for routine diagnostic
      purposes as well as for possible staging of the disease. Further, the multi
      component origin of the fluorescence spectra is illustrated by curve resolution
      and fluorescence spectra of separated proteins of tissue homogenates.

PMID- 16450392
TI  - Evolution and development of Hertwig's epithelial root sheath.
AB  - Periodontal regeneration and tissue engineering has re-awakened interest in the
      role of Hertwig's Epithelial Root Sheath (HERS), an epithelial tissue layer first
      discovered in amphibians more than a century ago. Using developmental,
      evolutionary, and cell biological approaches, we have, therefore, performed a
      careful analysis of the role of HERS in root formation and compared our data with
      clinical findings. Our developmental studies revealed HERS as a transient
      structure assembled in the early period of root formation and elongation and,
      subsequently, fenestrated and reduced to epithelial rests of Malassez (ERM). Our
      comparative evolutionary studies indicated that HERS fenestration was closely
      associated with the presence of a periodontal ligament and a gomphosis-type
      attachment apparatus in crocodilians and mammals. Based on these studies, we are
      proposing that HERS plays an important role in the regulation and maintenance of
      periodontal ligament space and function. Additional support for this hypothesis
      was rendered by our meta-analysis of recent clinical reports related to HERS
      function.

PMID- 16450395
TI  - Cytokine-containing gelfoam implants at a postsurgical tumor excision site to
      stimulate local immune reactivity.
AB  - We previously demonstrated increased numbers of CD34(+) progenitor cells in the
      peripheral blood of tumor bearers. Also demonstrated was the feasibility of
      chemoattracting these cells by sponge implants containing VEGF. The present study
      used a murine Lewis lung carcinoma (LLC) model to test if CD34(+) cells that are
      chemoattracted to a tumor excision site can be differentiated in situ into
      dendritic cells and whether this leads to increased local immune reactivity.
      After surgically excising established LLC tumors, mice received at the excision
      site gelatin sponge implants containing VEGF to chemoattract CD34(+) cells,
      and/or GM-CSF plus SCF to induce CD34(+) cell differentiation into dendritic
      cells. In some studies, lysates of GFP-transfected LLC cells (LLC(GFP)) were also
      included in the implants as a source of tumor antigen. After 2 weeks, implants
      and local lymph nodes were removed and analyzed. Implants containing VEGF, GM
      CSF/SCF or VEGF/GM-CSF/SCF had a higher proportion of CD34(+) cells compared to
      control implants. However, the number of dendritic cells was higher in implants
      containing GM-CSF/SCF or VEGF/GM-CSF/SCF than those containing either VEGF or
      diluent. Regional lymph node from mice containing GM-CSF/SCF or VEGF/GM-CSF/SCF
      implants showed increased dendritic cell levels. However, when lysates from
      LLC(GFP) were added to the implants, the highest proportion of dendritic cells
      associated with GFP was in lymph nodes of mice containing GM-CSF/SCF implants.
      Lymph node cells from mice with GM-CSF/SCF or VEGF/GM-CSF/SCF had a higher level
      of proliferation and IFN-gamma secretion in response to in vitro LLC lysate
      challenge, with the greatest response being from lymph node cells of mice with GM
      CSF/SCF implants. These results suggest the feasibility of using GM-CSF/SCF
      containing implants to increase dendritic cell levels, uptake of tumor antigens,
      trafficking to lymph nodes and stimulation of immune reactivity at tumor excision
      sites with residual tumor.

PMID- 16450396
TI  - Dynamic expression patterns of zebrafish 1G5 (1G5z), a calmodulin kinase-like
      gene in the developing nervous system.
AB  - Evolutionarily well-conserved Ca(2+)/calmodulin-dependent protein kinase (CaMK)
      proteins are known for their role as Ca(2+) signaling mediators. 1G5 encodes a
      CaMK like protein, which belongs to a calmodulin (CaM) kinase gene family. Here,
      we report the isolation of zebrafish homologue of mammalian 1G5, which we named
      1G5z. 1G5z is composed of three major domains: (1) an N-terminal serine/threonine
      kinase domain, (2) a central calmodulin-binding domain, and (3) a C-terminal
      alanine-rich domain, the 1G5z-specific domain. 1G5z shares 83 approximately 84%
      homology with other vertebrate 1G5 proteins. Spatiotemporal expression studies
      found that 1G5z is expressed by means of zygotic transcription and appears in
      various neuronal tissues from the 20-somite stage. 1G5z transcripts are more
      regionalized in the brain and spinal cord at 24 hr postfertilization (hpf). At 35
      hpf, 1G5z transcripts are exclusively present in the anterior trunk spinal cord
      as well as in the hindbrain, tegmentum, hypothalamus, and telencephalon. This
      expression pattern lasts until 48 hpf but ceases in the trunk. At 72 hpf, 1G5z is
      abundantly transcribed particularly in the specific region of the tectum and eye.
      We further observed that the number of 1G5z-positive cells is dramatically
      increased in the mindbomb mutant embryos but abolished in the trigeminal ganglion
      and caudal trunk sensory neuron of the neurogenin1 morphant at 24 hpf. In
      addition, bromodeoxyuridine staining further confirmed that the 1G5z-positive
      cells were postmitotic sensory and interneurons.

PMID- 16450397
TI  - A prospective study of dietary salt intake and gastric cancer incidence in a
      defined Japanese population: the Hisayama study.
AB  - The results of prospective studies of the association between dietary salt intake
      and gastric cancer occurrence remain controversial. To examine this issue in a
      cohort study of a general population, 2,476 subjects aged 40 years or older were
      stratified into 4 groups according to the amount of daily salt intake: namely,
      <10.0, 10.0-12.9, 13.0-15.9, and > or = 16.0 per day and were followed up
      prospectively for 14 years. During the follow-up period, 93 subjects developed
      gastric cancer. The age- and sex-adjusted incidence was significantly higher in
      the second to fourth groups than in the first group (age- and sex-adjusted hazard
      ratio [95% confidence interval], 2.42 [1.24-4.71] for the second group; 2.10
      [1.03-4.30] for the third group; 2.98 [1.53-5.82] for the fourth group). This
      association remained substantially unchanged even after adjusting for other
      confounding factors such as age, sex, Helicobacter pylori infection, atrophic
      gastritis, medical history of peptic ulcer, family history of cancer, body mass
      index, diabetes, total cholesterol, physical activity, alcohol intake, smoking
      habit and other dietary factors. In the stratified analysis, a significant salt
      cancer association was observed only in subjects who had both Helicobacter pylori
      infection and atrophic gastritis (age- and sex-adjusted hazard ratio, 2.87 [1.14
      7.24]). Our findings suggest that high dietary salt intake is a significant risk
      factor for gastric cancer; moreover, this association was found to be strong in
      the presence of Helicobacter pylori infection with atrophic gastritis.

PMID- 16450398
TI  - Cigarette smoking, elevated fasting serum glucose, and risk of pancreatic cancer
      in Korean men.
AB  - Pancreatic cancer is one of the most fatal human cancers and continues to be a
      major unsolved health problem. The goal of this study was to estimate the
      independent effects and interactions between cigarette smoking and diabetes on
      the risk of pancreatic cancer in Korean male population. Cigarette smoking and
      the risk of incidence and death from pancreatic cancer were examined in a 10-year
      prospective cohort study of 446,407 Korean men aged 40 to 65 years who received
      health insurance from the National Health Insurance Corporation and who had a
      medical evaluation in 1992. Relative risks (RR) and 95% confidence intervals (CI)
      were calculated using a Cox proportional hazards model after adjusting for age,
      body mass index, exercise and alcohol use. Current smoking was associated with an
      increased risk of incidence (RR = 1.7, 95% CI = 1.6-1.9) and mortality (RR = 1.6,
      95% CI = 1.4-1.7) from pancreatic cancer. The RR for pancreatic cancer increased
      with both duration and amount of smoking. Diabetes was also associated with an
      increased risk of both incidence (RR = 1.8, 95% CI = 1.5-2.2) and mortality (RR =
      1.7, 95% CI = 1.4-2.1) from pancreatic cancer. There was no interaction between
      smoking and fasting serum glucose in terms of pancreatic cancer risk. Thus, our
      prospective study has demonstrated that cigarette smoking and elevated fasting
      serum glucose are independently associated with an increased risk of pancreatic
      cancer in a large cohort of Korean males.

PMID- 16450399
TI  - Metabolic syndrome as a prognostic factor for breast cancer recurrences.
AB  - Several studies have shown that hormonal, metabolic and inflammatory mechanisms
      may affect breast cancer progression. We tested the prognostic value of metabolic
      syndrome in 110 postmenopausal breast cancer patients, who participated in a 1
      year dietary intervention study. The risk of adverse events after 5.5 years of
      follow-up was examined by Cox' proportional hazard modelling, adjusting for
      hormone receptor status, stage at diagnosis and serum testosterone level, which
      were shown to significantly affect prognosis. The adjusted hazard ratio of
      recurrence for the presence of metabolic syndrome at baseline was 3.0 (95% CI 1.2
      7.1). Combining metabolic syndrome and serum testosterone, the adjusted hazard
      ratio of recurrence among women with metabolic syndrome and testosterone levels
      higher than 0.40 ng/ml (median value) was 6.7 (95% CI 2.3-19.8) compared with
      that among women without metabolic syndrome and testosterone levels < or =0.40
      ng/ml. The results suggest that metabolic syndrome may be an important prognostic
      factor for breast cancer.

PMID- 16450400
TI  - Vascular anatomy of the developing medaka, Oryzias latipes: a complementary fish
      model for cardiovascular research on vertebrates.
AB  - The zebrafish has become a very useful vertebrate model for cardiovascular
      research, but detailed morphogenetic studies have revealed that it differs from
      mammals in certain aspects of the primary circulatory system, in particular, the
      early vitelline circulation. We searched for another teleost species that might
      serve as a complementary model for the formation of these early primary vessels.
      Here (and online at http://www.shigen.nig.ac.jp/medaka/atlas/), we present a
      detailed characterization of the vascular anatomy of the developing medaka embryo
      from the stage 24 (1 day 20 hr) through stage 30 (3 days 10 hr). Three
      dimensional images using confocal microangiography show that the medaka, Oryzias
      latipes, follows the common embryonic circulatory pattern consisting of ventral
      aorta, aortic arches, dorsal aorta, transverse vessels, vitelline capillary
      plexus, and marginal veins. The medaka, thus, may serve as a valuable model
      system for genetic analysis of the primary vasculature of vertebrates.

PMID- 16450401
TI  - Molecular characterization of adenocarcinoma and squamous carcinoma of the
      uterine cervix using microarray analysis of gene expression.
AB  - In an attempt to understand the molecular mechanisms for the different clinical
      features between adenocarcinoma/adenosquamous carcinoma (AC/ASC) and squamous
      carcinoma (SC) of the uterine cervix, we analyzed gene expression profiles of
      different histological subtypes of cervical cancer. Cancer specimens and the
      surrounding normal tissue counterparts were separately collected from cervical
      cancer patients undergoing type III radical hysterectomy. Paired total RNA
      (cancer and normal tissues) was isolated and analyzed with cDNA microarrays
      containing duplicate spots of 7 334 sequence-verified human cDNA clones. Selected
      differentially expressed genes specific for AC or SC were further verified using
      real-time quantitative polymerase chain reaction (RTQ-PCR) and
      immunohistochemistry. Genes, including CEACAM5, TACSTD1, S100P and MSLN were
      upregulated in AC. Contrarily, genes involved in epidermal differentiation
      complex such as S100A9 and ANXA8 were upregulated in SC. Cross-validation of the
      results using an independent but comparable group of patients with known long
      term outcomes (n = 63, median follow-up 70.3 months; range, 4-208 months) showed
      that the correlation between the selected 6 differentially expressed genes and
      histology was highly significant. CEACAM5 (p < 0.0001) and TACSTD1 (p = 0.009)
      were significant prognostic factors by multivariate Cox proportional hazards
      regression analysis. The combination of cDNA microarray, RTQ-PCR and
      immunohistochemical results of this study showed that it is possible to define
      different gene profiles for AC and SC. Moreover, TACSTD1 expression may be a
      novel poor prognostic factor.

PMID- 16450402
TI  - DLG5 variants contribute to Crohn disease risk in a Canadian population.
AB  - Variants in the gene encoding the DLG5 scaffolding protein have been reported to
      be associated with increased risk of inflammatory bowel disease (IBD) and
      particularly Crohn's disease (Crohn disease; CD). These findings have not been
      uniformly replicated in follow-up studies. In this study we genotyped a cohort of
      402 Canadian CD and 179 ulcerative colitis (UC) patients and 537 healthy controls
      for three IBD/CD-associated DLG5 variants. Our data reveal that the common DLG5
      haplotype (A), which was previously considered protective for IBD, is associated
      with modest increases in risk for IBD (P=0.02) and CD (P=0.04). The effects of
      haplotype copy number on risk for IBD were minor, with the odds ratio (ORs) being
      1.37 for the heterozygous risk genotype and 1.7 for the homozygous risk genotype.
      While we were unable to replicate the proposed association between the DLG5
      c.113G>A variant and IBD, an association of IBD (P=0.02) and CD (P=0.04) with the
      rarer c.4136C>A variant was replicated in this cohort. These associations were
      restricted to the non-Jewish subjects in this cohort and were not detected in the
      Ashkenazi Jewish population studied here. Within the non-Jewish group, no
      associations were detected between the DLG5 variants and specific phenotypic
      features, such as site of disease, and there was no evidence of epistasis between
      DLG5 and any of the CD-associated CARD15 or SLC22A4/A5 gene variants. Together,
      the results indicate a role for DLG5 variants in IBD susceptibility and suggest
      that further studies are warranted to evaluate this role in different IBD
      populations and to determine the functional pathways that couple DLG5 variants to
      IBD.

PMID- 16450403
TI  - Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic
      hyperglycinemia.
AB  - Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism characterized
      by accumulation of glycine in body fluids and various neurological symptoms. NKH
      is caused by deficiency of the glycine cleavage multi-enzyme system with three
      specific components encoded by GLDC, AMT, and GCSH. We undertook the first
      comprehensive screening for GLDC, AMT, and GCSH mutations in 69 families (56,
      six, and seven families with neonatal, infantile, and late-onset type NKH,
      respectively). GLDC or AMT mutations were identified in 75% of neonatal and 83%
      of infantile families, but not in late-onset type NKH. No GCSH mutation was
      identified in this study. GLDC mutations were identified in 36 families, and AMT
      mutations were detected in 11 families. In 16 of the 36 families with GLDC
      mutations, mutations were identified in only one allele despite sequencing of the
      entire coding regions. The GLDC gene consists of 25 exons. Seven of the 32 GLDC
      missense mutations were clustered in exon 19, which encodes the cofactor-binding
      site Lys754. A large deletion involving exon 1 of the GLDC gene was found in
      Caucasian, Oriental, and black families. Multiple origins of the exon 1 deletion
      were suggested by haplotype analysis with four GLDC polymorphisms. This study
      provides a comprehensive picture of the genetic background of NKH as it is known
      to date.

PMID- 16450404
TI  - Regular aspirin use and esophageal cancer risk.
AB  - Given the high mortality rate and the rapidly increasing incidence rate of
      esophageal carcinoma, chemopreventive agents are highly desirable. Aspirin has
      been shown to be associated with reduced risk of developing colorectal carcinoma
      and other cancers. Even though previous studies have shown reduced risk of
      esophageal cancer associated with aspirin use, results were inconsistent with
      respect to frequency and duration of use. In this hospital-based case-control
      study, 163 esophageal cancer cases were compared to 482 age- and sex-matched
      hospital controls with nonneoplastic conditions. Participants were classified as
      regular aspirin users if they had taken the drug at least once a week for 6
      months. Results suggest that esophageal cancer risk is significantly lower for
      regular aspirin users compared to nonusers [adjusted odds ratio (aOR) 0.54; 95%
      confidence interval (CI) 0.36-0.86]. Individuals who used an equivalent of at
      least 1 aspirin a day (> or =7 tablets/week) were half as likely to have been
      diagnosed with esophageal carcinoma (aOR 0.47; 95% CI 0.26-0.85), and a linear
      trend was noted with increasing frequency of use (p(trend) 0.007). Similar
      protective effects were noted with < or =20 years of use, whereas no risk
      reduction was noted with >20 years of use. Consistent reduction in risk
      associated with aspirin use was noted among both the major histological subtypes,
      but the protective effect appears to be more pronounced in adenocarcinoma
      compared to squamous cell carcinoma. Overall, results from the current study
      suggest that regular aspirin use may be associated with reduced risk of
      esophageal cancer.

PMID- 16450406
TI  - Interpretation of surface EMGs in children with cerebral palsy: An initial study
      using a fuzzy expert system.
AB  - Surface EMG detected simultaneously at different muscles has become an important
      tool for analysing the gait of children with cerebral palsy (CP), as it offers
      essential information about muscular coordination. However, the interpretation of
      surface EMG is a difficult task that assumes extensive knowledge and experience.
      As such, this noninvasive procedure is not frequently used in the general
      clinical routine. An Artificial Intelligence (AI) system for interpreting surface
      EMG signals and the resulting muscular coordination patterns could overcome these
      limitations. To support such interpretation, an expert system based on fuzzy
      inference methodology was developed. The knowledge-base of the system implemented
      15 rules, from which the fuzzy inference methodology performs a prediction of the
      effectiveness of the muscular coordination during gait. Our aim was to assess the
      feasibility and value of such an expert system in clinical applications. Surface
      EMG signals were recorded from the tibialis anterior, soleus muscle, and
      gastrocnemius muscles of children with CP to assess muscular coordination
      patterns of ankle movement during gait. Nineteen children underwent 114 surface
      EMG measurements. Simultaneously, the gait cycles of each patient were determined
      using foot switches and videotapes. From the EMG signals, the effectiveness of
      the ankle movement was predicted by the expert system, and predictions were
      classified using a three-point ordinal scale. In 91 cases (80%), the clinical
      findings matched the predictions of the expert system. In 23 cases (20%) the
      predictions of the expert system differed from the clinical findings with 12
      cases revealing worse and 11 cases revealing better results in comparison to the
      clinical findings. As this study is a first attempt to verify the feasibility and
      correctness of this expert system, the results are promising. Further study is
      required to assess the correlation with the kinematic data and to include the
      whole leg.

PMID- 16450405
TI  - Effects of 2-hydroxypropyl-beta-cyclodextrin and cholesterol on porcine sperm
      viability and capacitation status following cold shock or incubation.
AB  - Porcine sperm are extremely sensitive to the damaging effects of cold shock. It
      has been shown that cholesterol-binding molecules, such as 2-hydroxypropyl-beta
      cyclodextrin (HBCD), improve post-cooling porcine sperm viability when added to
      an egg yolk-based extender, but also enhance sperm capacitation in other species.
      The objective of this study was to determine the effects of HBCD and cholesterol
      3-sulfate (ChS) on porcine sperm viability and capacitation following cold shock
      or incubation under conditions that support capacitation using a defined medium.
      We report here that porcine sperm incubated in medium containing both HBCD and
      ChS have significantly improved viability following cold shock (10 min at 10
      degrees C) when compared to sperm incubated without HBCD or ChS, or with either
      component alone. Treatment with HBCD plus ChS also completely inhibited the
      increase in protein tyrosine phosphorylation induced by the cold shock treatment
      or by incubation for 3 hr under conditions that support capacitation. Two assays
      of sperm capacitation, the rate of calcium ionophore-induced acrosome reactions
      and chlortetracycline (CTC) staining, were not significantly altered by HBCD and
      ChS following cold shock. However, 3-hr incubation with HBCD plus ChS or with 1
      mM ChS alone decreased the percentage of sperm undergoing the induced acrosome
      reaction without significantly affecting viability when compared to the control.
      These results indicate that the manipulation of sperm plasma membrane cholesterol
      content affects porcine sperm viability and capacitation status and could
      therefore be useful to protect sperm from cold shock during cryopreservation by
      improving viability without promoting premature capacitation.

PMID- 16450407
TI  - HOXD10 M319K mutation in a family with isolated congenital vertical talus.
AB  - Congenital vertical talus (CVT) is a primary dislocation of the talonavicular
      joint that often occurs in neuromusculoskeletal syndromes, but may also be seen
      as an isolated abnormality. Six families with isolated CVT were ascertained. DNA
      was isolated from 21 affected individuals and 17 unaffected individuals from
      these families, as well as from five sporadic patients with CVT. Variable
      expressivity was noted in three families, manifesting as clubfoot in three
      individuals. Genome-wide linkage analysis generated a maximum two-point logarithm
      of odds score on chromosome 2q with D2S1353 (Zmax = 1.43 at theta(max) = 0.1), 17
      Mb from the HOXD gene cluster. DNA from one affected individual of each family
      was subjected to mutational analysis of the HOXD10 gene. A single missense
      mutation was identified (M319K, 956T > A) in the homeodomain recognition helix of
      the HOXD10 gene that segregated with disease in one large British family. This
      mutation was recently described in a family of Italian descent with CVT and
      Charcot-Marie-Tooth deformity HOXD10 gene mutations were not identified in any of
      the other families or sporadic patients with CVT, suggesting that genetic
      heterogeneity underlies this disorder.

PMID- 16450408
TI  - A bioactive sol-gel glass implant for in vivo gentamicin release. Experimental
      model in Rabbit.
AB  - Biomaterial pieces with osteogenic properties, suitable for use in the treatment
      of bone defects, were synthesized. The materials, which avoid bone infections,
      are exclusively composed of gentamicin sulfate and bioactive SiO2-CaO-P2O5 sol
      gel glass (synthesized previously), and were manufactured by means of uniaxial
      and isostatic pressure of the mixed components. After implanting the pieces into
      rabbit femur, we studied (1) antibiotic release, determining the concentration in
      proximal and distal bone, liver, kidney, and lung as a function of time, and (2)
      bone growth as a consequence of the glass reactivity in the biological
      environment. The results demonstrated that the implants are good carriers for
      local gentamicin release into the local osseous tissue, where they show excellent
      biocompatibility and bone integration. Moreover, these implants are able to
      promote bone growth during the resorption process.

PMID- 16450409
TI  - Mitochondrial organization in prepubertal goat oocytes during in vitro maturation
      and fertilization.
AB  - The aim of this study was to evaluate mitochondrial distribution during in vitro
      maturation (at 0, 15, 20, and 27 hr of IVM) and fertilization of prepubertal goat
      oocytes compared to mitochondrial distribution of ovulated and in vitro
      fertilized oocytes from adult goats. Oocytes from prepubertal goats were
      recovered from a slaughterhouse and were matured in M199 with hormones and serum
      for 27 hr. Ovulated oocytes were collected from gonadotrophin-treated Murciana
      goats. Frozen-thawed spermatozoa were selected by centrifugation in Percoll
      gradient and were capacitated in DMH with 20% steer serum for 1 hr. Ovulated and
      IVM-oocytes were inseminated in DMH medium with steer serum and calcium lactate
      for 20 hr. Oocytes and presumptive zygotes were stained with Mitotraker Green FM
      and observed under a confocal laser scanning microscope. Ultrastructural
      morphology of oocytes and presumptive zygotes were analyzed by transmission
      electron microscopy (TEM). Prepubertal goat oocytes at germinal vesicle stage
      (GV) presented mitochondria localized in the cortical and perinuclear region. IVM
      oocytes at metaphase II presented mitochondria peripheral polarized to the region
      opposite were the metaphase spindle is positioned and within the polar body.
      Ovulated oocytes presented peripheral mitochondria distribution and mitochondrial
      aggregation around the MII spindle. At 20 hr post-insemination, mitochondria were
      distributed around the two synchronous pronuclei (2PN rpar; in zygotes ovulated
      oocytes whereas in prepubertal 2PN-zygotes mitochondria presented a peripheral
      polarized distribution. Images by TEM detected that immature prepubertal goat
      oocytes that are less electrodense and present fewer cristae than in vitro
      matured prepubertal goat oocytes; these are characterized by being associated to
      swollen vesicles. Mol. Reprod. Dev. 73: 617-626, 2006 (c) 2006 Wiley-Liss, Inc.

PMID- 16450410
TI  - Efficient and simple production of transgenic mice and rabbits using the new DMSO
      sperm mediated exogenous DNA transfer method.
AB  - A high efficient and simple transgenic technology on mice and rabbits to
      transfect spermatozoa with exogenous DNA/DMSO complex to obtain transgenic
      offspring, which is namely called DMSO-sperm mediated gene transfer (SMGT). Mouse
      sperm could be either directly transfected via injection into testis or cultured
      in vitro with the plasmed DNA containing the enhanced green fluorescent protein
      (EGFP) that could be expressed in the embryos and offspring. Then, 36 living
      transgenic rabbits were produced using the same technology, and the transgenic
      ratio of 56.3% was detected using PCR and Southern blot. As the controls, the
      transgenic ratios of 39.6% and 47.8% have also been tested using the liposomes
      mediated technology of Tfx-50 Reagent or Lipefectamin-2000, respectively. The
      results show that the female transgenic rabbits, as the mammary gland bioreactor
      models, could express the human tissue plasminogen activator mutant (htPAm) in
      their mammary cells when they are adult.

PMID- 16450411
TI  - The role of ARPC4 in tip growth and alignment of the polar axis in filaments of
      Physcomitrella patens.
AB  - When the actin related protein 2/3 (Arp2/3) complex member arpc4 was deleted in
      Physcomitrella patens (moss), the resulting null mutant (Deltaarpc4) was viable
      and revealed no gross changes during morphogenesis of filaments into
      gametophores. However, we observed a striking reduction of filamentous tip
      growth, resulting in smaller, denser colonies. Although polar responses of
      Deltaarpc4 filaments to unilateral white light were unaffected, these mutant
      filaments were defective in their response to polarized white light. These
      observations strongly suggest a specific role of the Arp2/3 complex as a
      downstream target for signals regulating oriented tip growth. Insertion of YFP
      ARPC4 into Deltaarpc4 rescued the mutant phenotypes and localized ARPC4
      exclusively to the tip cell of filaments, the site of actin dynamics and
      polarized growth. The ability of Deltaarpc4 to perform some but not all cellular
      responses will allow the study of its function in orientation of tip growth in
      response to directional cues (e.g. light) in a viable but mutated background.

PMID- 16450412
TI  - Psychometric properties of the Dutch version of the posttraumatic growth
      inventory among cancer patients.
AB  - In the current study, we investigated the psychometric properties of a Dutch
      translation of the posttraumatic growth inventory in a heterogeneous group of
      cancer patients. Its original five-factor structure was maintained. The internal
      consistency of the total scale, as well as its subdimensions, was satisfactory.
      As expected, the experience of posttraumatic growth was positively related to:
      emotional expression about the illness, openness to experience, and feelings of
      innerness. Furthermore, the scale appeared to be sensitive for the demographics
      age and gender. The experience of posttraumatic growth was not related to
      negative feelings such as avoidance, anxiety, depression, and neuroticism. Our
      Dutch translation of the instrument appeared to be a sound measure for the
      experience of posttraumatic growth in cancer patients.

PMID- 16450413
TI  - Waist-to-hip ratio indicates heart attack risk.

PMID- 16450415
TI  - Device reduces risk of falling in women with kyphosis.

PMID- 16450414
TI  - Exercise after 50 can add three years to life expectancy.

PMID- 16450416
TI  - OJ lowers arthritis risk.

PMID- 16450417
TI  - Depression worsens from one generation to the next.

PMID- 16450418
TI  - Aggressive treatment of ACF saves lives.

PMID- 16450419
TI  - Use of B6 and/or folic acid fails to lower cardiovascular events.

PMID- 16450420
TI  - Eating fish may slow decline in mental skills.

PMID- 16450421
TI  - Pancreatic cancer found earlier with 3-D MRI.

PMID- 16450422
TI  - Struggling to hear can impact word memory.

PMID- 16450423
TI  - Lately I have been getting a lot of bruises on the tops of my hands for no
      reason. What's causing this bleeding?

PMID- 16450424
TI  - I'm going to have hip replacement surgery next month. What can I expect to
      undergo or experience prior to surgery?

PMID- 16450425
TI  - I see that some juice companies are adding vitamin D to their orange juice. Is
      this an effective way to get vitamin D? Would I still need a supplement?

PMID- 16450426
TI  - Cancer survivorship: resilience across the lifespan. Proceedings of the National
      Cancer Institute's and American Cancer Society's 2002 Cancer Survivorship
      Conference. June 2-4, 2002. Washington, DC, USA.

PMID- 16450427
TI  - Bibliography. Current world literature. Immunology.

PMID- 16450428
TI  - Cervical cancer prevention - a paradigm shift?

PMID- 16450429
TI  - Optical detection of cervical neoplasia: results from an internally-controlled
      multicenter study.

PMID- 16450431
TI  - Active coping mediates the association between religion/spirituality and
      functional well-being in ovarian cancer.

PMID- 16450430
TI  - A clinical study of the use of impedance spectroscopy in the detection of
      cervical intraepithelial neoplasia (CIN).

PMID- 16450432
TI  - [Abstracts of the 14th annual meeting of the Ophthalmologists Society of Saxony
      Thuringia. 25-26 November 2005, Haldensleben].

PMID- 16450433
TI  - [Syndromes of peripheral nervous system lesions and mechanisms of their formation
      in disorders of connective tissue].
AB  - Systemic rheumatoid diseases are often concomitant with the development of
      central and peripheral systems pathologies. Presented are the results revealing
      high frequency of peripheral nervous system lesions (lupus erythematosus and
      systemic scleroderma), which characterized by polyneuropathy and tunnel
      syndromes. Based on the results of literature and own studies, pathological
      mechanisms of peripheral nervous system lesions in diffusion disorders of
      connective tissue were singled out as follows: ischemic, immunological and
      metabolic. Taking these mechanisms into account will permit to conduct
      pathogenetically valid therapy and to improve its results.

PMID- 16450435
TI  - Bullying among elementary schoolchildren.

PMID- 16450434
TI  - [A study of mydocalm efficiency in the treatment of chronic headache of tension].
AB  - Mydocalm was used for the treatment of 31 patients, mean age 45 +/- 4 years, with
      chronic headache of tension in a dosage of 150 mg 3 times per day during 4 weeks.
      Twenty-six patients have completed the therapy course. Before- and after
      treatment, neurological status, dynamics of psychoautonomic disorders, an extent
      of anxiety and depression, quality of sleep, quality of life, pain syndrome
      measured by a number of tests, were assessed, along with electromyography and
      examination of nociceptive reflex. Subjective evaluation of the drug efficacy was
      taken into account as well. A marked positive effect of mydocalm was observed in
      70% of patients, moderate effect--in 30%. A predictor of mydocalm efficacy was
      severity of muscle tonic syndrome.

PMID- 16450436
TI  - Overweight and risk of muscle, bone and joint problems in children...and some
      help may be on the way.

PMID- 16450437
TI  - Whooping cough outbreaks in Kansas.

PMID- 16450438
TI  - Child safety. Backpacks and back pain in children.

PMID- 16450439
TI  - Support groups with heart. You don't have to go it alone--support groups offer
      information and more.

PMID- 16450441
TI  - The best prescription money can't buy. Conflicting recommendations on exercise
      obscure the main message: just do it.

PMID- 16450440
TI  - A numbers game worth playing. Knowing the numbers for a few key risk factors is
      good for your heart and overall health.

PMID- 16450442
TI  - Leftover drugs pose prescription for trouble. Few programs exist for
      environmentally safe drug disposal. Flushing them is a no-no.

PMID- 16450443
TI  - Shining a light on stealth fats. No more hunting for evidence of trans fats in
      your food. Now you can find it right on the label.

PMID- 16450444
TI  - Ask the doctor. When I go to bed at night, I feel a pulsing in my head above my
      left ear. I never feel this when I am sitting or standing. I have high blood
      pressure and have had three bypasses. Is this something I should be worried
      about?

PMID- 16450445
TI  - Ask the doctor. My rheumatoid arthritis gives me trouble in spite of my
      medications. I have read that statins, in addition to lowering cholesterol, also
      calm inflammation. Would taking a statin help my arthritis?

PMID- 16450446
TI  - How to keep those New Year's resolutions. Psychologists have identified
      successful ways of meeting self-determined goals, but they may not work if you're
      a perfectionist.

PMID- 16450447
TI  - How to handle a hangover. Drinking fluids may help with the morning-after misery
      from getting drunk.

PMID- 16450448
TI  - Gallbladder surgery. Most people who have their gallbladders removed are glad to
      see them go, but for a small percentage, the operation seems to cause bowel
      problems.

PMID- 16450449
TI  - Patient, protect thyself? Studies show that you can, as a patient, spot and
      possibly prevent a medical error from happening to you.

PMID- 16450450
TI  - Could high blood pressure be causing your headache? The pendulum has swung back
      and forth on the connection between hypertension and headaches. A recent study
      find they could be related.

PMID- 16450451
TI  - By the way, doctor. I've had thrush three times this year. I read that it can be
      connected to stress, but also to serious diseases. One doctor told me I was
      "somatizing." What is thrush and could it be related to something?

PMID- 16450452
TI  - By the way, doctor. I developed acute urinary retention after having a pacemaker
      put in. I'm a 90-year-old man and in pretty good shape considering my age, but
      I'd rather not have any more procedures. What are my options?

PMID- 16450453
TI  - Control and eradication strategies of avian influenza in Mexico.
AB  - In December 1994, a highly pathogenic (HP) avian influenza (AI) outbreak occurred
      in Mexico, caused by the subtype H5N2, affecting two main regions of egg and
      poultry-meat production. At that time, governmental actions included immediate
      stamping out of the affected flocks, disinfection of affected premises,
      quarantine measures in the region, strict movement controls on poultry and their
      products and vaccination. With these policies, the disease was eradicated in a
      relatively short time. The last case of HPAI was detected in June 1995 and the
      country was declared as free of HPAI virus in January 1996 to the World Animal
      Health Organisation (OIE). Since then, Mexico has maintained a control programme
      against low pathogenic (LP) AI virus that is based on a zoning classification,
      movement controls and other strategies.

PMID- 16450454
TI  - Research of the magnetic nanometer liposome of emodin.
AB  - OBJECTIVE: In order to enhance the biological availability of emodin inside the
      body, develop the method of preparing the magnetic nanometer liposome of emodin.
      METHODS: Used membrane-ultrasound method to prepare the magnetic nanometer
      liposome of emodin. RESULTS: The particle diameter of the magnetic nanometer
      liposome of emodin was about 100-300nm, and its envelopment rate was 33.75%.
      CONCLUSION: It is easy and feasible to use membrane-ultrasound method to make the
      magnetic nanometer liposome of emodin, and the envelopment rate of emodin is to
      be further enhanced.

PMID- 16450455
TI  - Artisan aphakic intraocular lens implantation in cases of subluxated crystalline
      lenses due to Marfan syndrome.
AB  - PURPOSE: To assess implantation of an Artisan aphakic intraocular lens (IOL) in
      cases with subluxated lenses due to Marfan syndrome. METHODS: Retrospective study
      of a small case series comprised of seven eyes (two children and three adults)
      with subluxated lenses due to Marfan syndrome that underwent lens extraction and
      Artisan aphakic IOL implantation. Best spectacle-corrected visual acuity and
      endothelial cell status were the key elements of follow-up examinations. RESULTS:
      No complications occurred during surgery. Visual acuity was improved by > or = 4
      Snellen lines in all seven eyes. These results were maintained at the last follow
      up. Endothelial cell status remained constant in all cases at 6-month follow-up.
      CONCLUSIONS: In seven eyes with a subluxated crystalline lens due to Marfan
      syndrome, implantation of an Artisan aphakic IOL improved visual acuity while
      preserving anterior chamber status.

PMID- 16450456
TI  - Nasal paraganglioma: a case report.
AB  - Paragangliomas are tumors of the autonomic nervous system, arising from
      paraganglionic tissue. Paragangliomas of the head and neck region are very rare.
      In the head and neck, the most common sites of origin of this neoplasm are the
      carotid body, the jugular bulb and the vagal body. Paragangliomas of the nose and
      paranasal sinuses are very uncommon. The authors referred one case of nasal
      paraganglioma in a 45-year-old male patient, who was submitted to surgical
      excision, and included clinical findings, diagnostic criteria, treatment,
      prognosis and literature review. The importance of reporting this case refers to
      the rare incidence of paragangliomas in the nasal cavity and paranasal sinuses.

PMID- 16450457
TI  - Topical testosterone treatment in idiopathic micropenis.

PMID- 16450458
TI  - Obesity in adolescents living in Mediterranean countries: the report of
      Mediterranean Action Group on Adolescent Medicine (MAGAM), Castriadas Cagliari,
      Italy, 24 October 2003.

PMID- 16450460
TI  - When the doctor is in, but you wish he wasn't.

PMID- 16450459
TI  - Case reopens abortion issue for justices.

PMID- 16450461
TI  - French, in first, use a transplant to repair a face.

PMID- 16450462
TI  - Korean scientist said to admit fabrication in a cloning study.

PMID- 16450463
TI  - Clone scandal: "a tragic turn" for science.

PMID- 16450464
TI  - Drugs, devices and doctors.

PMID- 16450466
TI  - Doctors' delicate balance in keeping hope alive.

PMID- 16450465
TI  - Global trend: more science, more fraud.

PMID- 16450467
TI  - Under a microscope: high-profile cases bring new scrutiny to science's
      superstars.

PMID- 16450469
TI  - Abortion rights in Latin America.

PMID- 16450468
TI  - Korean cloning scientist quits over report he faked research; backers of stem
      cell work fear larger setback.

PMID- 16450470
TI  - "Come again?" Good medicine requires clarity.

PMID- 16450471
TI  - It may look authentic; here's how to tell it isn't: a scientific journal shows
      the way in a new offensive against fraud.

PMID- 16450472
TI  - In article, doctors back ban on drug companies' gifts; concerns cited on quality
      of patient care.

PMID- 16450473
TI  - Plantar ulcers and eyebrow-hair paucity.

PMID- 16450474
TI  - The next abortion decision.

PMID- 16450476
TI  - In appreciation of Lawrence C. Katz, 1956-2005.

PMID- 16450475
TI  - Korean leaves cloning center in ethics furor; admits lying on source of donated
      eggs.

PMID- 16450477
TI  - [Ogata Koan and Soeda Gensyun: the completion of the house of the president of
      the Western Medical School].
AB  - Ogata Koan had an official relationship with Soeda Gensyun as a doctor of the
      Western Medical School in August of Bunkyu 2 (1862), when Ogata became the
      president of the school. At that time, the president's residence had not been
      completed, so he lived in a temporary house. Ogata visited Soeda's house to
      borrow it. The reason why the completion of the president's house was delayed was
      that Shogun Iemoti, his wife, and Tensyoin suffered from measles, and Ito Genboku
      resigned as the court physician (okuisi). Soeda made efforts for the marriage of
      Nanae, Koan's daughter, to Otsuki Gensyun, the first son of Otsuki Synunsai.

PMID- 16450478
TI  - [A brief history of biographical Seishu Hanaoka].
AB  - It was 1804 when Seishu Hanaoka (1760-1835), performed an excision of the breast
      cancer of a patient named Kan Aiya under general anesthesia by Mahutu-san. This
      is the first documented general anesthesia in the world. Numerous studies have
      been made about Seishu Hanaoka during the past 100 years and among them the
      monograph titled "Seishu Hanaoka and His Surgery" by Shuzo Kure published in
      1923, had been thought to be nearly perfect and it had been thought that nothing
      had been left unsolved concerning the biography of Hanaoka. The present author
      made an exhaustive investigation of the monograph in terms of anesthesiology and
      found a serious forgery in the transcription of Hanaoka's "Nyugan chiken roku".
      The author also detected two forged photographs of the record in Kure's book. As
      Kure was a professor of psychiatry of the Tokyo Imperial University and a leading
      medical historian at that time, other investigators of Hanaoka followed him
      unquestioningly and they could not reveal Kure's forgery for 80 years since its
      publication. Because of Kure's forgery the biographical study of Hanaoka was
      retarded seriously and incorrect information about him has prevailed. The cause
      of the academic retardation is considered to have been mainly due to the lack of
      a bibliographical survey of original documents of Hanaoka by following
      investigators.

PMID- 16450479
TI  - [Prof. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery,
      Kyoto University, and his achievements in orthopaedic surgery in the Meiji Era of
      Japan (part 1: establishment of the department)].
AB  - The Department of Orthopaedic and Musculoskeletal Surgery, Graduate School of
      Medicine, Kyoto University (formerly the Department of Orthopaedic Surgery, Kyoto
      Medical School, Kyoto Imperial University) was founded by Imperial Ordinance,
      Article No. 89 issued on April 23, 1906. On May 4, 1906, Dr. Shinichiro Asahara,
      Assistant Professor of the Department of Surgery, was appointed as the first
      director of the Department of Orthopaedic Surgery, Kyoto Medical School, Kyoto
      Imperial University. Dr. Michiharu Matsuoka, Assistant Doctor of the Department
      of Surgery, Tokyo Medical School, Imperial University of Tokyo, was appointed
      Assistant Professor of Surgery, Kyoto Medical School, Kyoto Imperial University
      in March 1901. From August 1903 to May 1906, he studied orthopaedic surgery in
      Germany and returned on May 5, 1906. Dr. Matsuoka was appointed as the director
      and chief of the Department on May 13, 1906 and took over Dr. Asahara's position.
      On June 18, 1906, Dr. Matsuoka started his clinic and began giving lectures on
      orthopaedic surgery. This was the first department of orthopaedic surgery among
      the Japanese medical schools. Dr. Matsuoka was appointed as Professor in 1907. He
      had to overcome several obstacles to establish the medical department of a new
      discipline that had never existed in Japanese medical schools. This article
      discusses Dr. Matsuoka's contributions to establishing and developing orthopaedic
      surgery in Japan in the Meiji-era.

PMID- 16450480
TI  - [In memory of Dr. Naoichi Tsuyama].

PMID- 16450482
TI  - Canine parvovirus: from not there to everywhere: a historical look at the
      emergence, media coverage, and vaccine development of canine parvovirus.

PMID- 16450481
TI  - Defining the threat: American veterinarians and bovine tuberculosis eradication
      in the World War II era.

PMID- 16450483
TI  - Attempting to make practice acts perfect.

PMID- 16450484
TI  - Forgotten veterinarians 5. The doctors Ruth and death in the Superstition
      Mountains.

PMID- 16450485
TI  - Old and mad in Victorian Oxford: a study of patients aged 60 and over admitted to
      the Warneford and Littlemore Asylums in the nineteenth century.
AB  - This is a historical case note analysis of older patients admitted to the
      Warneford and Littlemore Asylums in nineteenth-century Oxford. Of 1044 admissions
      to the Warneford, 93 patients were aged over 60 (8.9%). At Littlemore, 998 of a
      total of 5464 admissions were aged over 60 (18.3%). High levels of
      psychopathology were found, as in other studies examining patients of all ages,
      and were similar for the two institutions. The largest difference was in the
      death rate, which was much higher for Littlemore Asylum. This resulted from the
      preponderance of patients with organic diagnoses who were admitted to Littlemore,
      many of whom died shortly afterwards.

PMID- 16450486
TI  - The impact of mood stabilizers on bipolar disorder: the 1890s and 1990s compared.
AB  - This study comparing patterns of service utilization by bipolar patients in North
      West Wales found a greater prevalence of service utilization in the 1990s
      compared with the 1890s. In the pre-lithium era, admissions for bipolar disorders
      occurred at a rate of 4 every 10 years; they now occur at a rate of 6.3 every 10
      years. Where 100 years ago, there were 16 bipolar patients per million population
      resident per day in hospital, there are now 24 per million resident in acute
      service beds and more in non-acute beds. These data are incompatible with simple
      claims that mood stabilizing drugs 'work'. An alternative is that these agents
      have treatment effects, and further research is needed to match treatments to
      patients in order to optimize outcomes.

PMID- 16450487
TI  - New directions for the Archives.

PMID- 16450489
TI  - FTC report on mail-order PBMs "gives green light to policymakers".

PMID- 16450488
TI  - Taking information technology to the next level.

PMID- 16450490
TI  - Association health plans: deja vu all over again.

PMID- 16450491
TI  - Health plan sponsored personal health records: a tool for information driven
      quality improvement.

PMID- 16450492
TI  - Bringing evidence-based medicine into the physician's office.

PMID- 16450493
TI  - High-tech, high-touch: home-based telemedicine is expanding access to care and
      maximizing resources.

PMID- 16450494
TI  - Lessons learned from chameleons.

PMID- 16450495
TI  - Nonprofit health plan governance practices: drawing on the best in both worlds.

PMID- 16450496
TI  - Your landline should not be a provider's lifeline: how to reduce calls with
      online provider service.

PMID- 16450497
TI  - Not all health content is created equal.

PMID- 16450498
TI  - Automated tools help health plans' members control prescription drug costs.

PMID- 16450499
TI  - The evolution of information management: moving to an active warehouse.

PMID- 16450500
TI  - Endovascular procedures in critical leg ischemia of elderly patients.
AB  - PURPOSE: Purpose of this study was to evaluate angiographic and clinical results
      of popliteal, infrapopliteal, and multi-level disease percutaneous transluminal
      angioplasty (PTA) in over-80 years old patients with chronical clitical leg
      ischemia. In fact such patients with extensive peripheral vascular disease and
      critical limb ischemia (CLI) are generally poor surgical candidates. METHODS:
      Between 1998 and 2003, 37 elderly patients aged 80-89 years old (mean age 83.3)
      with critical leg ischemia were treated with PTA. All patients were at high
      surgical risk. 31/37 (81.5%) patients had chronic non-healing wounds, and 14/37
      (37%) had multi-level disease of superficial femoral, popliteal and crural
      arteries. One hundred and two lesions were treated by angioplasty. Immediate
      angiographic and 1 year clinical results were retrospectively analyzed. RESULTS:
      The overall procedural success rate was 32/37 (84.2%). There were three major
      complications (7.9%), but no deaths, and three technical failures, all were of
      infrapopliteal lesions. After 1 year, 27 patients could be followed, five
      patients died during the first year of unrelated causes. Twenty-three patients
      (85.2%), were clinically re-occluded within 1 year, but complete and partial
      wound healing was achieved in 80% (16/20) and rest pain improvement in 57% (4/7),
      so that overall limb salvage was 74% (20/27). CONCLUSIONS: Elderly patients with
      multi-level CCLI have a short patency term following angioplasty of 14.8% after 1
      year. Nevertheless, this temporary vascular patency enables wound healing or
      improvement in 74% of these patients, thus such endovascular interventions are
      recommended in this age group.

PMID- 16450501
TI  - Nosocomial infections in colo-rectal surgery of the old patient.
AB  - Every surgical act, especially in geriatric age, can be a relevant moment in the
      onset of nosocomial infections. This has a peculiar aspect in patient who undergo
      colo-rectal surgery, both in election and especially in emergency, in which the
      simple opening of intestines always involves a minimal contamination. In order to
      reduce the incidence of infections, and therefore the septic complications of
      this surgery, it is necessary to pay attention to the preparation of the surgical
      equipe, of the operating room, of the surgical instruments and, in election, to
      the careful preparation of the patient through a careful evaluation of the
      possible bio-umoral alterations, in order to correct them. The results of our
      experience allow us to say that the prevention of post-operatory sepsis find its
      main moment in the careful evaluation and eventual correction of the nutritional
      status, in the stimulation of the immune system, in the antibiotic prophylaxis
      both parenteral and topical, and, last but not least, in a correct surgical
      technique. All this is particularly important for patients affected by colo
      rectal neoplastic and inflammatory diseases, for which the intestinal bacteria,
      more virulent in weak and fragile patients, often represent the source of
      contamination that can start a sepsis and then assume an important part in
      determining the final result of surgery.

PMID- 16450502
TI  - Large incisional hernia in the elderly: which kind of treatment?
AB  - Incisional hernia is one of the commonest long-term complications of open
      abdominal surgery. Especially in old patients (over 70 years), the incisional
      hernias represent an invalidating pathology whose treatment, for the high
      incidence of associated respiratory and cardiovascular disease, offers
      difficulties related to the preoperative and postoperative management as well as
      to the surgical treatment. This paper reports the Author's experience about the
      surgical treatment of large incisional hernia (> 10 cm) with open prosthetic mesh
      repair in geriatric patients.

PMID- 16450503
TI  - Laparoscopic colorectal surgery in the elderly.
AB  - BACKGROUND: The efficacy and safety of laparoscopic colorectal surgery have been
      demonstrated in several well designed trials in recent years. At the same time
      the experience in the field of laparoscopy in the elderly has increased. The aim
      of this study was to evaluate retrospectively the experience of laparoscopic
      colorectal surgery in patients over 75 years in our unit. DESIGN: Retrospective
      study. SETTING: Surgical Department, San Lorenzo Hospital, Valdagno (VI).
      SUBJECTS AND METHODS: All the patients over 75 years, out of a total number of
      121 unselected patients, undergoing laparoscopic colectomy or laparoscopic
      abdomino-perineal resection between June 2002 and May 2005. MAIN OUTCOME
      MEASURES: Postoperative mortality, operating time, conversion rate, morbidity,
      time of discharge from hospital. RESULTS: Six patients were converted to open
      surgery. 87 patients over 75 years underwent laparoscopic colorectal surgery.
      There was no postoperative death, in three cases a reoperation was done, because
      of postoperative intestinal obstruction in one case (over 75) and for anastomotic
      fistula in two (one over 75, after low anterior resection). Mean operative time
      was was 180 minutes (range 150-300). CONCLUSIONS: Laparoscopic colorectal surgery
      in elderly patients is a safe group of procedures for benign and malignant
      lesions of large bowel, resulting in a low rate of complications even if the time
      of operation is increased compared with open procedures. Postoperative pain and
      hospital stay, with return to normal life, are decreased compared with open
      surgery.

PMID- 16450504
TI  - Peroperative control of surgical infections.
AB  - The overall incidence of post-surgical infection actually amount to 3-10%, in
      different multicentric trial, although the data may underrepresent the true
      incidence of such infections owing to increase of day-surgery. Antibiotic
      prophylaxis rapresents the first choice in the management of surgical patients,
      which standardization and selection can determine a real protection for all the
      operating time. Standardization of intraoperative procedure, considering utility
      of a multistep precautionary measure and the weight of these measures on post
      operative stay of patients, may be an arm for control really post-operative
      infectious complications, according with control of sterilization's procedures
      and diffusion of dedicated device.

PMID- 16450506
TI  - Venous thromboembolism: which patients are truly at risk?
AB  - In clinical practice there are several conditions that are at relatively high
      risk of venous thromboembolism (VTE). However, not all patients included in the
      high risk category will actually develop VTE, and not all patients in the low
      risk category are protected against this eventuality. A high risk of VTE is
      associated with orthopedic or major surgery; a relative risk is associated with
      laparoscopic surgery, intermediate risk is associated, for instance, with
      oncology. In conclusion, individuals with deficiencies of natural anticoagulants,
      homozygotes due to mutation of Factor V Leiden or prothrombin and individuals
      with multiple risk factors may be defined as "high risk".

PMID- 16450505
TI  - Gastric cancer in the elderly patient.
AB  - The incidence of gastric cancer is increasing in elderly patients, unlike what
      it's being observed in the younger patients. The aim of this study is to evaluate
      the impact of the age on the resecability, resection type (R0-R1-2), morbidity,
      mortality and survival rate. The higher mortality observed in the elderly
      patients, the discussed role of an extended lymphadenectomy and the poor survival
      rate, would lead to a surgical approach which mostly tends to the palliation of
      the symptoms than the obtainment of a curative resection. But, on the other hand,
      the impossibility of making chemotherapy in most of the over 75 year old
      patients, lead us to a R0 surgery treatment.

PMID- 16450507
TI  - New devices for inguinal hernia repair in elderly patients.
AB  - A recent meta-analysis concluded that there was a lower incidence of recurrences
      after mesh hernioplasty, as opposed to non-mesh open methods. Inguinal mesh and
      plug hernioplasties have been performed using prostheses of different sizes and
      shapes, either sutured or not to the tissues. However, hernia repair using mesh
      is sometimes associated with postoperative pain, more or less severe and/or
      persistent. As a consequence it may interfere with the time required to return to
      work and to normal daily activities. Finally, concerning the postoperative
      complications and recurrences, the data presented in our study confirm the very
      low rate for both aspects; then, as regards the time to return to work, our good
      results are similar to those of other studies available in literature. In
      conclusion the tension-free hernia repair described, based upon the use of
      Prolene 3D patch, is a safe operation, simple to be acquired, it can be performed
      on an outpatient basis, with a low complication rate, a low level of pain, and an
      excellent quality of life thereafter. The new device seems to satisfy all
      requisites of a feasible, reliable and effective system for repairing primary
      inguinal hernia, at low cost, high patient comfort, and with low risk of
      recurrences.

PMID- 16450508
TI  - Oesophageal achalasia in elderly people: results of the laparoscopic Heller-Dor
      myotomy.
AB  - AIMS: To assess the outcome of laparoscopic Heller-Dor myotomy for oesophageal
      achalasia in two groups of patients identified by age (under and over 70 years)
      using functional and clinical instruments. BACKGROUND: Current therapies for
      achalasia can't restore normal motility but can palliate dysphagia. Many other
      symptoms may persist difficult to quantify and to compare. In order to understand
      if age is a factor that influences the therapeutic outcome we tested the
      reliability of a specific QoL instrument for comparing outcomes of surgery for
      achalasia. METHODS: Functional examinations and the Gastrointestinal Quality of
      Life Index (GIQLI) were used before and after laparoscopic Heller-Dor myotomy.
      RESULTS: Starting in January 1996, 28 consecutive patients of 32 diagnosed
      (instrumental evidences) achalasia were operated on laparoscopically for various
      clinical stages of achalasia. In 78% of patients dysphagia disappeared, the
      incidence of gastro-oesophageal reflux was of 11%. The patients completed a GIQLI
      questionnaire preoperatively and after a minimum postoperative follow-up of 1
      year. Median preoperative GIQLI score was 78(range 38-109) out of a theoretical
      maximum score of 144. At a median follow-up of 35 months (range 18-72), the score
      had significantly improved to 115 (range 71-140). All the items assessing
      gastrointestinal symptoms and physical, social, and emotional function were
      significantly improved. There is no difference between the two groups identified.
      CONCLUSIONS: The laparoscopic Heller-Dor myotomy is an effective palliation for
      acalasia, the medium-term outcome is not affected by the age of the patients. The
      GIQLI is a reliable instrument to compare the impact of achalasia symptoms on
      health-related QoL.

PMID- 16450509
TI  - Inguinal hernia surgery performed on elderly cardiopath patients.
AB  - Old age cannot be considered as an absolute risk factor in the surgical treatment
      of inguinal hernia, which can also be stated for the majority of elderly people
      pathologies. The opportunity of surgically treating a wider range of individuals
      has been made possible thanks to the use of both modern, less invasive surgical
      techniques and easy-to-handle anaesthetic medicines, as well as a new concept of
      elderly-customer-friendly sanitary planning. The evaluation of the risks is
      multifactorial; consequently, in the case of elderly cardiopath individuals,
      suffering from inguinal hernia, one has to reconsider both the type of
      anaesthetic and the surgical technique to be performed, in view of the increased
      risks, as against the case of non cardiopath, elderly patients. The modern
      tension-free techniques have demonstrated in cardiopath patients the same
      advantages which have been observed in elderly non cardiopath patients, such as a
      faster functional recuperation as well as no significant percentage difference
      related to the early and late complications following the operation.

PMID- 16450510
TI  - The aged patient who has undergone an operation in the intensive care unit.
AB  - The reaching of 13% within the Italian population of those who are older than 70
      has caused a significant rise in the number of the elder people who undergo major
      surgery operations; this is due also to the availability of mini-invasive endo
      laparoscopic techniques, to the availability of new very manageable anaesthetics
      and new anaesthesia plans, suitable for the elder, to a more effective control of
      post-operative pain, and mostly to a comfortable access to I.C.U. in the post
      operative phase.

PMID- 16450511
TI  - Palliative surgery for gastric cancer in elderly patients.
AB  - Poor survival rate of elderly patients affected by locally advanced or metastatic
      gastric cancer is related to primary tumour complications. Bleeding is the most
      important adverse event, other major complications are gastric outlet obstruction
      and nutritional deprivation. Rarely the patients will perforate the stomach
      cancer and there is a sudden end to their life; contamination of the ascites
      result in a rapid death. Thus, an aggressive approach toward palliation of this
      condition is resection: in this manner the expected survival is approximately one
      year. Derivation techniques or endoscopic treatments are applied in those
      patients whose operative risk is inacceptable; in these cases poor median
      survival is expected. The aim of this report in to refer about the experience in
      palliative surgery for gastric cancer in the Department of Geriatric Surgery of
      the University of Padua.

PMID- 16450512
TI  - The treatment of inguinal hernia in the elderly: open technique or laparoscopic
      approach?
AB  - Well defined and shared quality standards characterize the ideal treatment of
      inguinal hernia: it should be the least traumatic as regards both the requested
      type of anaesthesia and the operative technique and the least expensive; it
      should have the least per-and post-operative morbidity. The chosen technique
      should be also the easiest to learn and to perform; and his positive results
      should be the most reproducible. While there are a lot of studies about the
      comparison between open and laparoscopic surgery, the number of the studies about
      the specific evaluation of the problem in the aged is very limited. Aim of the
      paper is to aid in evaluation of the problem in a group of patients, on the basis
      of the reports and on an initial departmental experience. In conclusion the
      laparoscopic repair is a complementary choice and not an alternative to the open
      surgery in the elderly patients.

PMID- 16450513
TI  - Gastrointestinal tumours in elderly.
AB  - The Authors report their experience concerning 129 cases of gastrointestinal
      neoplasms (gastric, colonic, anorectal), recorded during the last years among
      patients aged between 70 and 81 years, who underwent radical surgery. The main
      issues evaluated were: anaesthesiological risk, stage, post-operative mortality
      and morbidity. Elderly seems not to be a contraindication, nor a limit for
      surgery if the patient is correctly and strictly managed pre and post
      operatively.

PMID- 16450514
TI  - Quality of life assessment in geriatric surgery.
AB  - An excessive number of studies on health-related quality of life (HRQOL) has
      rendered results often contradictory and difficult to interpret. HRQOL evaluation
      in the aged is even more difficult, due to intrinsic conceptual and
      methodological problems. Since no structured instruments are available for use in
      geriatric surgery, it would be necessary either to work out a new specific
      instrument or to adapt/adopt an already existing method. Properties and
      methodological steps for development and validation are set forth. The Functional
      Assessment for Cancer Therapy (FACT) scale was developed for patients with cancer
      and has been recently validated also in the elderly. The Multidimensional
      Assessment for Cancer in the Elderly (MACE) was originally developed for elderly
      cancer patients. Since both methods are irrespective of subjects undergoing
      surgery, its use requires further validation. The MACE gives a broad information
      spectrum, but in geriatric surgery it seems too complex. The FACT-G is a simple
      core item questionnaire which can be integrated by disease-specific items and
      seems more compliant. A disease-specific and treatment-specific application of
      FACT questionnaires by multicenter studies might be useful in evaluating surgical
      procedures in patients in whom significant advantages in survival cannot be
      expected, but QOL can still significantly improve.

PMID- 16450515
TI  - Carotid endarterectomy under local anesthesia in elderly: is it worthwhile?
AB  - Carotid endarterectomy (CEA) has a positive effect on stroke free survival in
      patients with either symptomatic or asymptomatic severe carotid bifurcation
      stenosis. However, most trials have excluded elder patients. In addition,
      concerns have arisen regarding the benefits of CEA in the elderly population,
      especially in women. In this study, we performed an outcome analysis in patients
      undergoing CEA comparing those eighty and older to their younger counterparts. A
      total of 262 carotid operations were performed under local anaesthesia between
      1998 and 2004; 76 (34%) were carotid reconstructions in 70 patients over 75 yr of
      age. Twenty patients (26%) presented with asymptomatic critical stenosis.
      Transient ischemic symptoms were the reason for presentation in 35 patients
      (46%). Progressive stroke was documented in two patients (3%) and a stroke with
      persisting neurological deficit was demonstrated in 19 cases (25%). Coronary
      artery disease was present in 47 patients (38%) and arterial hypertension in 55
      (72%). Fifty-nine patients (84%) were classified as ASA group 3. Seventy-one
      thromboendarterectomies of the carotid bifurcation with direct closure were
      performed. Five patients had other types of reconstruction. Postoperative
      complications occurred in three patients. One had a transient neurological
      deficit and another a lethal stroke; the third patient died from myocardial
      infarction. The in-hospital mortality was 2.9%, which was not significantly
      higher than the results of the reconstructions in younger patients (1.5%).
      Surgery for carotid artery occlusive disease under local anaesthesia can be
      safely performed in selected patients of more than 75 yr of age.

PMID- 16450516
TI  - The use of artificial dermis in the treatment of chronic and acute wounds:
      regeneration of dermis and wound healing.
AB  - Wounds with large loss of deep tissue can be repaired using a dermis substitute.
      When wounds have an irregular fund, applying a skin graft on these one can be a
      failure. Integra Dermal Regeneration Template is a bilaminate material, a
      collagen chondroitin-sponge overlayed with silicone. It heals wounds where
      conventional methods of repair fail or are too risk. This study analizes
      Integra's use for chronic and pathological wounds in 7 patients. Applied to
      wounds reduces inflammation and protects it from a possible contamination or
      another injury. Imbibition, fibroblast migration, neovascularization, remodeling
      and maturation are distinct histologic phases of forming neodermis. Trough the
      silicon layer is possible to observe the histogenesis: the change in color of the
      matrix is a predictor of its vascularization. When the color has progressed from
      pink through pale yellow and finally to peach, the neodermis is fully
      vascolarized. The postoperative care is minimum. Integra is removed after three
      weeks regenerating a new dermal tissue. So it can be applied a thin skin graft
      until healing of all patients.

PMID- 16450517
TI  - The treatment by V.A.T.S. and M.A.C. of secondary neoplastic pleural effusion in
      the old patient (> 70 years).
AB  - A secondary malignant pleural effusion is a common event in the evolution of some
      tumours. It is frequent in advanced phase, above all the breast cancer in the
      woman and the cancer of the lung in the man, but such pathology can interest also
      extra-thoracic cancers (ovary, colon, prostate, etc.) and the malignant lymphoma.
      In the majority of cases in order to obtain a good control of the effusion entity
      with reduction of the respiratory symptoms and improvement of the quality of
      life, palliative local therapy is indispensable. Numerous methods and substances
      have been proposed in the time for the treatment of the N.P.E. The talc
      pleurodesis executed in the old patients (> 70 years) by means of the V.A.T.S.
      "one trough" and "Monitored Anaesthesia Care" (MAC) has shown valid procedure for
      the control of the secondary neoplastic pleural effusion, with little uneasiness
      for the patients, reduced complications and a sure effectiveness.

PMID- 16450518
TI  - Cardiovascular risk factors in Saudi Arabian and non-Saudi Arabian diabetic
      patients in Saudi Arabia.
AB  - To determine frequency of cardiovascular risk factors in Saudi and non-Saudi
      diabetics, we studied patients attending King Abdulaziz University Hospital for
      follow-up in the period January 1997 to December 2001. Cardiovascular risk
      factors, including hypertension, hyperlipidaemia, obesity and smoking, were
      studied as well as degree of blood glucose control. Of 1122 patients in the
      study, 48% were Saudis and 52% non-Saudis. No statistically significant
      difference was found for prevalence of cardiovascular risk factors between the
      two groups. Correlation of each of the risk factors to patient's age showed
      significant correlation to hypertension and smoking.

PMID- 16450519
TI  - Clustering of cardiovascular risk factors among Omani adults.
AB  - To determine the distribution and correlates of clustering of cardiovascular
      disease (CVD) risk factors, data from the Oman National Health Survey, 2000 were
      analysed. Based on demographic data (blood pressure, fasting blood glucose, serum
      cholesterol, weight, height, waist and hip measurements), 5660 subjects were
      grouped according to how many of four CVD risk factors (hypertension, high
      cholesterol, diabetes, overweight/obesity) they had. We found that 72% of
      subjects had less than one risk factor and 2% had all four. Older age exacerbated
      risk, while living in rural areas or being single was protective. Metabolic
      cardiovascular syndrome is a public health problem in Oman. Increasing awareness
      in healthcare providers and the wider population by comprehensive dissemination
      of the survey results is crucial.

PMID- 16450520
TI  - Burden of coronary heart disease on the Iranian oil industry (1999-2000).
AB  - To estimate the direct cost of coronary heart disease (CHD) to the Iranian oil
      industry, we calculated the cost of essential services for 1253 CHD patients
      admitted to the National Iranian Oil Corporation (NIOC) Central Hospital. The
      direct cost of CHD at the Hospital was 10940 million rials (US$ 1 = 8000 rials),
      or 8.7 million rials per patient. The direct cost of CHD to the Iranian oil
      industry was estimated at 22 770 million rials. Working days lost to workers
      hospitalized for CHD amounted to 62 832. The heavy burden of CHD on the Iranian
      oil industry necessitates the introduction of an industry-wide prevention
      programme.

PMID- 16450522
TI  - Current and never smokers: differentials in characteristics, knowledge and
      perceptions.
AB  - A cross-sectional interview survey of tobacco use was conducted in Alexandria,
      Egypt, comparing current smokers with never smokers. Among men, the risk of
      current tobacco use was significantly higher among married participants (OR =
      1.74), especially those with low educational or occupational status. In contrast,
      although few women smoked, tobacco use was significantly higher among those
      holding a university degree (OR = 15.33). Never smokers were significantly more
      knowledgeable than current smokers about tobacco-related health hazards. Never
      smokers had significantly better perceptions of the danger of tobacco use,
      susceptibility to health-related hazards and the benefits of being tobacco-free.
      Multivariate analysis revealed that tobacco use is independently predicted by
      participants' sex, age and educational attainment as well as their perceptions.

PMID- 16450521
TI  - Smoking patterns among primary health care attendees, Al-Qassim region, Saudi
      Arabia.
AB  - Prevalence, sociodemographic patterns and medical co-morbidity of smoking among a
      cross-section of primary health care (PHC) clients in Saudi Arabia were examined.
      We used a 44-item semistructured questionnaire to collect data from 1752 patients
      at 25 randomly selected PHC centres. Percentage of smoking was 52.3%. Although
      85% were adult smokers, 8.6% began smoking before age 12. Smokers gave
      overlapping reasons to smoke including peer pressure; non-smokers gave religious
      and health logics against smoking. Of all smokers, 92.8% wanted to learn
      cessation strategies, 11.8% were ignorant of hazards and 32.4% reported
      manifestations of nicotine withdrawal. Besides alcohol use (13.4%), 81.8% had co
      morbid physical disease.

PMID- 16450523
TI  - Hyperhomocysteinaemia, hyperlipidaemia and risk of venous thromboembolism in
      Shiraz.
AB  - To assess the risk of venous thromboembolism (VTE) associated with
      hyperhomocysteinaemia (hyper-Hcy) and hyperlipidaemia, we performed a case
      control study. Fasting total homocysteine (Hcy), triglyceride and cholesterol
      levels were assessed in 43 patients with VTE and 43 controls. Mean Hcy level was
      significantly higher in the test group. Odds ratio (OR) for VTE in patients with
      hyper-Hcy was 2.7, with the association stronger in women and those under 50. The
      OR for those with both hypertriglyceridaemia and hypercholesterolaemia was
      significantly greater in those under 50. Increased risk for venous thrombosis was
      found among those under 50 having both lipid abnormalities.

PMID- 16450524
TI  - Profile of acute poisoning cases presenting to health centres and hospitals in
      Oman.
AB  - A simple pro forma was used for a retrospective study of poisoning cases at 45
      health institutions in Oman during January-December 2000. No deaths were recorded
      among 2009 cases of acute poisoning. A quarter of all cases (55.8% of paediatric
      cases) were children aged 1-4 years. The largest category (59.5%) was animal
      bites and stings: 25.4% undiagnosed, 19.7% scorpion stings, 7.6% bee, spider or
      wasp stings and 6.8% snake bites. Next highest (38.5%) was ingestion of
      substances: 18.2% pharmaceuticals, 8.2% food and 4.7% household products. Most
      drug-related cases were due to paracetamol. Suicide attempts were recorded for
      6.0%. Collection of poisoning data through a central registry system is needed
      for the implementation and future assessment of prevention programmes.

PMID- 16450525
TI  - Pregnancies past the estimated date of confinement: labour and delivery outcome.
AB  - To compare labour and delivery outcomes in women undergoing induction and those
      having spontaneous onset for pregnancies past the estimated date of delivery, a
      prospective study of 395 singleton, uncomplicated pregnancies was performed.
      Labour was induced in 175 women. Overall caesarean section rate was 9.4%, with no
      significant difference between the 2 groups. Overall rate of assisted vaginal
      deliveries was 7%, higher in the induction group than the spontaneous onset group
      but the difference was not significant. There was no significant difference in
      occurrence of intrapartum meconium, nor for maternal morbidity. No neonate needed
      intubation. No perinatal deaths occurred. Perinatal mortality and morbidity are
      preventable, and induction of labour before 42 weeks is justifiable to prevent
      adverse outcomes.

PMID- 16450526
TI  - Breastfeeding indicators in Dakahlia governorate.
AB  - This study was carried out in Dakahlia Governorate to assess current
      breastfeeding practices using the standardized breastfeeding indicators developed
      by the World Health Organization and to highlight the impact of some
      socioeconomic and maternal factors on these indicators. An interview was carried
      out with mothers of 1200 infants and children < 24 months during a poliomyelitis
      immunization campaign in urban and rural areas. The findings indicate that 84.6%
      of infants aged 0-4 months are fully breastfed, with 42.5% and 42.1% of them
      exclusively and predominantly breastfed respectively. Rural infants are more
      likely to be exclusively breastfed, to continue breastfeeding for 1 year and to
      initiate breastfeeding early. Non-working mothers are more likely to breastfeed
      exclusively and more likely to continue breastfeeding for 1 year.

PMID- 16450527
TI  - Influence of mothers' characteristics on their perceptions and use of the growth
      chart.
AB  - Although growth charts are recommended for monitoring children, recent reports
      indicate poor use by mothers. We investigated maternal knowledge and perceptions
      of growth charts and identified characteristics affecting use. At outpatient
      paediatric clinics of a Riyadh hospital, 305 mothers with children under age 5
      were interviewed by questionnaire during May-June 2001. Overall awareness of
      growth charts was 35.8% and ever-use was 8.6%. Education, parity and number of
      living children were significantly associated with knowledge. Among mothers who
      ever used growth charts (8.7%), only 10% reported doctors recommended changes in
      health care because of them. Overall, 71% wanted to monitor their child's growth,
      but 20% did not know how. Increased health education in all health care delivery
      systems is needed.

PMID- 16450528
TI  - Acute rheumatic fever in Jordanian children.
AB  - Rheumatic fever remains a significant health problem in Jordan. We
      retrospectively reviewed medical charts of 28 boys and 22 girls (mean age at
      presentation 10.5 +/- 2.6 years) with confirmed diagnosis based on modified Jones
      criteria at Queen Alia Heart Institute from February 1999 to February 2002.
      Arthritis was the commonest major manifestation (88%; 68% migratory), carditis
      was second commonest (48%; 8% silent carditis) and chorea was seen in 6%. None
      had subcutaneous nodules or erythema marginatum. The mitral valve was most
      commonly affected (80%); both mitral and aortic valves were affected in 25%.
      Pericarditis was seen in 12.5% and acute congestive heart failure in 4%.
      Practitioners should be aware of diverse clinical presentations and emphasize
      strict adherence to prophylaxis guidelines.

PMID- 16450529
TI  - Co-morbidity and treatment of attention deficit hyperactivity disorder in Saudi
      Arabia.
AB  - To review the experience of a child psychiatric clinic regarding co-morbidity and
      treatment characteristics of children with attention deficit hyperactivity
      disorder (ADHD), a retrospective study was done on patients under 19 years who
      were attending the clinic and were diagnosed with ADHD. Co-morbidity and
      treatment characteristics were also studied. ADHD was diagnosed in 25.5% of the
      patients. Of these, 28.3% had coexistent expressive language disorder and 38.7%
      coexistent mild mental retardation. A psychostimulant (methylphenidate) was
      prescribed to 23.6% while antidepressants (primarily imipramine) were prescribed
      to 35.9%. Behavioural therapy was the most commonly offered psychotherapy.
      Antidepressants were used more than psychostimulants. Psychotropics had a more
      beneficial effect than psychotherapy.

PMID- 16450530
TI  - Inpatient child and adolescent psychiatric referrals in Saudi Arabia: clinical
      profiles and treatment.
AB  - A retrospective review was made of the case records of inpatients referred to the
      psychiatric consultation-liaison service of King Khalid University Hospital,
      Saudi Arabia over a 6-year period. For the 109 patients under 18 years old, the
      study noted both the medical or surgical diseases diagnosed as well as
      psychiatric disorders and the treatment approaches used by psychiatrists.
      Depressive and adjustment disorders were the most often diagnosed psychiatric
      illnesses. The most common medical diagnoses were epilepsy, drug overdose,
      ambiguous genitalia, orthopaedic injuries and diabetes mellitus. Young people
      with these medical problems are in real need of psychological assessment and
      intervention.

PMID- 16450531
TI  - Adolescent abuse in a community sample in Beni Suef, Egypt: prevalence and risk
      factors.
AB  - Adolescent abuse was studied in 555 school students (mean age 15.6 +/- 1.5 years)
      selected by multistage random sampling in Beni Suef in 1998. Each student
      received a general physical examination and a pre-coded questionnaire to identify
      determinants of abuse. Prevalence of abuse was 36.6%. Emotional, physical, sexual
      and combined abuse prevalence was 12.3%, 7.6%, 7.0% and 9.7% respectively.
      Significant predictors of sexual abuse were hyperactive child, disabled child,
      disinterested mother, low birth order child or wasted child. For physical abuse,
      significant predictors were maternal disinterest, maternal education and
      injuries. Significant predictors of emotional abuse were overcrowding, disease
      and mistreatment by a teacher. Violent behaviour was reported for more than 20%
      of the emotionally and the sexually abused.

PMID- 16450533
TI  - Outcome of azithromycin treatment of active trachoma in Omani school children.
AB  - A prospective cohort study was made of 386 first-grade primary-school children in
      Oman with active trachoma and 386 matched controls without trachoma. All children
      were educated about trachoma prevention. In addition, trachoma cases were treated
      with a single dose of oral azithromycin (20 mg/kg). Trachoma status was evaluated
      after 6 weeks, 6 months and 12 months. The follicles and inflammatory signs of
      active trachoma resolved 6 weeks or more after azithromycin treatment. The
      protection against subsequent trachoma infection cycles was optimal at 6 months
      (85.2% of cases, 99.0% of controls infection-free) but declined at 12 months
      (66.7% of cases, 98.2% of controls infection-free). Clinical evaluation seems to
      be a useful tool to evaluate the response of azithromycin to active trachoma
      cases in schoolchildren in a country with limited resources.

PMID- 16450532
TI  - Knowledge of and attitudes towards family planning by male teachers in the
      Islamic Republic of Iran.
AB  - A cross-sectional study was carried out on knowledge of and attitudes to family
      planning in male teachers working in the education system in Teheran. We found
      that 65% of the study population had acceptable knowledge regarding the issue.
      More than 95% of respondents reported having a favourable attitude towards the
      implementation of family planning programmes and about 90% believed that decision
      making regarding use of contraceptives should be a joint process. To improve the
      planning and administration of family planning programmes, the main variables
      identified in this study should be further investigated in different population
      groups. Addressing men in family planning programmes may improve their success
      and lead to increased contraceptive use.

PMID- 16450534
TI  - Tuberculin reactivity among health care workers at King Abdulaziz University
      Hospital, Saudi Arabia.
AB  - Tuberculosis is both a nosocomial and an occupational infection. The prevalence
      of positive tuberculin skin reactions at King Abdulaziz University Hospital,
      Saudi Arabia, was investigated by testing 298 health care workers. Conventional
      tuberculin skin testing was performed using 0.1 mL of purified protein derivative
      injected intracutaneously. After 48-72 hours, induration size was recorded. The
      prevalence of positive tests (induration > or = 10 mm) was 78.9% overall, 60.0%
      for Saudi Arabians compared with 81.8% for non-Saudi Arabians (P < 0.01). The
      mean response size (8.9 +/- 7 mm) for Saudis was also significantly lower than
      for non-Saudis (13.9 +/- 7 mm, P < 0.001). To enhance the protection of both
      health care workers and hospitalized patients, effective preventive measures and
      annual tuberculin testing of health care workers should be considered.

PMID- 16450535
TI  - Epidemiology of malaria in Al-Tameem Province, Iraq, 1991-2000.
AB  - To determine the rates of malarial infection in different areas of Al-Tameem
      province, we conducted a cross-sectional study from 1991 to 2000. We found an
      overall infection rate of 0.76% by Plasmodium vivax. Infection rates were highest
      in Dibis district (1.12%), followed by infections from outside the province
      (0.93%) and in Hawija district (0.89%), Kirkuk (0.62%) and Dakok (0.17%). Rates
      of infection varied by year with the lowest rate in 1991 (0.02%) and the highest
      rate in 1996 (1.84%). All ages were represented, with the highest rate of
      infection among 21-30-year-olds. Males had a slightly higher rate of infection
      (0.78%) than females (0.73%).

PMID- 16450536
TI  - Malaria and intestinal parasitosis among children presenting to the paediatric
      centre in Sana'a, Yemen.
AB  - We studied the profile of malaria and intestinal parasitosis among children
      presenting to the Paediatric Health Centre in Sana'a from January 1998 to
      December 2000. In stool samples from 9014 children, Ascaris lumbricoides,
      Entamoeba histolytica, Giardia lamblia and Trichuris trichiura were the most
      common. Infection with parasites of direct life-cycle were similar in boys and
      girls. Schistosome infection was significantly higher in boys than girls, but
      girls were more infected with ascariasis. The only species of malaria parasite
      found in blood samples from 753 children with suspected malaria was Plasmodium
      falciparum, with the highest rates in April-June. The majority of positive cases
      were Yemeni children, but 10.8% were Sudanese or Ethiopian.

PMID- 16450537
TI  - Selected epidemiological features of human brucellosis in Yazd, Islamic Republic
      of Iran: 1993-1998.
AB  - Brucellosis is a significant health problem in countries where control of
      zoonoses is inadequate. During 1993-98, we analysed sera and cultures from 792
      suspected brucellosis patients who presented with histories of fever, chills,
      night sweating, weakness, malaise and headache to the referral hospital in Yazd.
      Cases were investigated by tube agglutination test (TAT) and 2-mercaptoethanol
      test (2-MET) and a questionnaire was completed for each.TAT titre was > or = 1:1
      60 for 745 patients (94.1%) and 2-MET was positive for 42 (5.3%). Of 745
      confirmed cases, 460 were from 1996-1997. Prevalence was highest in summer
      (39.5%) and more common males than among females. Prevalence was highest among
      those aged 10-19 years (27.7%). Most patients had a history of infected cheese,
      milk and milk product consumption (98%).

PMID- 16450538
TI  - Epidemiology of acute renal failure in hospitalized patients: experience from
      southern Saudi Arabia.
AB  - Despite advances in health care, morbidity and mortality associated with acute
      renal failure (ARF) remain high. This study determined the frequency and etiology
      of ARF in hospitalized patients in Saudi Arabia over 2 years. Of the 150 cases of
      ARF, 38.0% were community-acquired and 62.0% hospital-acquired. The main cause
      was acute tubular necrosis (ATN) in 93 patients, due to sepsis (24.7%), ischaemia
      (12.7%), rhabdomyolysis (mainly from road traffic accidents) (10.7%), drugs
      (7.3%) and malaria and snake-bites (4.6%). Overall, 40% died, 48% made a full
      recovery and 1 patient (0.7%) became dialysis-dependant. Factors associated with
      poor prognosis were: age 60+ years, community-acquired ARF, peak blood urea
      nitrogen > 160 mg/dL, duration of ARF > 1 week, need for dialysis and associated
      chronic liver disease.

PMID- 16450539
TI  - Microbiology of wound infection after caesarean section in a Jordanian hospital.
AB  - To determine the microbiology of wound infection following caesarean section and
      to evaluate the use of Gram stain for the predicton of subsequent microbiological
      culture results, 1319 surgical wounds were followed up. We did Gram stains and
      cultures on exudates from open wounds and on aspirates if the wounds had
      demonstrable fluid collection. Incidence of post-caesarean wound infection was
      8.1%. Ninety-three (86.9%) of 107 infected wounds were culture positive, with
      Staphylococcus aureus the most frequently found organism (42%). Organisms seen by
      Gram stain yielded a sensitivity of 96.6%, specificity of 88.9%, positive
      predictive value of 97.7% and negative predictive value of 84.2% when used to
      predict positive culture results for bacterial wound infection.

PMID- 16450541
TI  - Innovative learning approaches in an established medical school: the experience
      at JUST in Jordan.
AB  - The Faculty ot Medicine at Jordan University of Science and Technology was
      established in 1986. Innovative changes were introduced to the traditional
      subject-based, hospital-oriented curriculum in 1999, the objectives of which were
      to integrate student learning, emphasize student-centred learning, develop
      training in a community setting, and introduce elective learning packages. To
      evaluate the integrated learning in the new curriculum, we assessed the validity
      and reliability of students' scores. The scores for the integrated 'modules' were
      compared with those in general subjects studied in the traditional way. Our study
      showed that results of tests taken on the new 'modules' are both valid and
      reliable measures of students' performance.

PMID- 16450540
TI  - [Attitudes of general practitioners to pharmaceutical sales representatives in
      Sousse].
AB  - The therapeutic knowledge of physicians is the corner stone to the rational use
      of medicines; however information about medicines is generally obtained from the
      pharmaceutical industry via their sales representatives (reps). We aimed to
      identify general practitioners' (GPs) attitudes to pharmaceutical reps and the
      information they provide. We surveyed 140 GPs using a self-administered
      questionnaire. The response rate was 78% (72 GPs from the public sector and 68
      from the private sector). About 10% of the GPs said they received daily visits
      from pharmaceutical reps; 84% of GPs considered them an efficient source of
      information and 31% said they might change their therapeutic prescribing
      following visits from these reps. Because of their positive perception of
      pharmaceutical reps, GPs are susceptible to the information they provide.
      Controlling the validity of the therapeutic information imparted by the
      pharmaceutical industry is thus a fundamental component of the programme for the
      rational use of medicines.

PMID- 16450542
TI  - [Cortisol rhythm during the month of Ramadan].
AB  - We studied the nyctohemeral cortisol secretion rhythm and the cortisol response
      to 1-24 corticotropin during Ramadan in 11 healthy, male volunteers aged 20-35
      years. Their response to 250 mg 1-24 corticotropin was investigated 2 weeks
      before Ramadan by testing daily at 08:00 and 20:00 hours. After 16-22 days of
      fasting, their cortisol levels were measured at 08:00 hours and their response to
      1-24 corticotropin at 20:00 hours. Before Ramadan, the baseline cortisol level
      was significantly higher at 08:00 hours than at 20:00 hours and the cortisol
      response to 1-24 corticotropin was also higher at 08:00 hours but this difference
      was not significant. During Ramadan, the cortisol level at 08:00 hours was lower
      than at the same time before Ramadan; the level at 20:00 hours was slightly
      higher than at the same time before Ramadan. There was no significant difference
      between the cortisol response to 1-24 corticotropin at 20:00 hours during Ramadan
      and the responses before Ramadan at 20:00 hours and 08:00 hours.

PMID- 16450543
TI  - [Metabolic effects of the month of Ramadan fasting on type 2 diabetes].
AB  - We assessed the effects of Ramadan fasting on metabolic control, particularly
      change of HDL-cholesterol in 25 type 2 diabetic patients treated with diet or
      oral agents, with good metabolic control. Clinical and biochemical parameters and
      food intake were evaluated 3 weeks before Ramadan, in the fourth week of Ramadan
      and 3 weeks after Ramadan.There were no changes in body weight and blood pressure
      nor any metabolic complications. The mean plasma fasting glucose, serum
      fructosamin and haemoglobin A1c did not change. We found a negative relation
      between cholesterol intake during Ramadan and the change of HDL-cholesterol. When
      cholesterol intake was lower than 400 mg/day, plasma HDL-cholesterol increased by
      13% at the end of Ramadan and by 23% 3 weeks after Ramadan.

PMID- 16450544
TI  - Effect of water softening on the colour intensity of routine haematoxylin and
      eosin stain.
AB  - Haematoxylin and eosin (H&E) is the most popular routine stain used in pathology
      laboratories for highlighting cellular structures. To study the effect of tap
      water'softening' (i.e. calcium extraction) on H&E stains, 5 sets of slides from
      30 different paraffin-embedded human pathologic tissue blocks were prepared in
      the same way except for washing with 5 different types of water. Slides washed in
      untreated tap water showed the best results concerning differentiation and colour
      intensity, while slides washed with softened or other treated water showed poorer
      degrees of differentiation and colour intensity. The worst results were obtained
      from slides washed with water containing sodium bicarbonate. Low calcium and
      magnesium ions and high sodium ions in soft water adversely affect the results of
      routine H&E stain.

PMID- 16450545
TI  - The diabetes prevention and control programme of the Islamic Republic of Iran.
AB  - Diabetes mellitus has become a monumental problem and a major health concern
      throughout the world. We report on the programme developed by the Islamic
      Republic of Iran for control and management of diabetes, which involves screening
      for type 2 diabetes in adults at risk and a systematic approach for delivery of
      health care to people with diabetes.

PMID- 16450546
TI  - Screening for type 2 diabetes in the Iranian national programme: a preliminary
      report.
AB  - Diabetes mellitus is a significant threat to public health. It is estimated that
      more than 1.5 million people with diabetes live in the Islamic Republic of Iran.
      We report on the preliminary results of the national programme for the prevention
      and control of type 2 diabetes which began in 1996. The pilot project has so far
      been instituted in 17 provinces. Of 595 717 people aged 30 years and over, 247
      518 were classed as at risk and 3.6% had diabetes, 4.3% of women and 2.6% of men.
      Diabetes prevalence varied from 1.3% in rural areas to 14.5% in large cities.
      Early detection and control strategies are aimed at diminishing the heavy burden
      of diabetes.

PMID- 16450547
TI  - Kiss of the Benchuca--Chagas' disease presenting with transient third-degree
      atrioventricular block.

PMID- 16450549
TI  - The perfect Christmas gift.

PMID- 16450548
TI  - From "hear" to there.

PMID- 16450550
TI  - The Chief--a comparison of medical school education and the teaching methods of
      Jesus Christ.

PMID- 16450551
TI  - All I want for Christmas is my flu vaccine.

PMID- 16450552
TI  - Births: preliminary data for 2004.
AB  - OBJECTIVES: This report presents preliminary data for 2004 on births in the
      United States. U.S. data on births are shown by age, race, and Hispanic origin of
      mother. Data on marital status, tobacco use, prenatal care, cesarean delivery,
      preterm births, and low birthweight (LBW) are also presented. METHODS: Data in
      this report are based on 99.1 percent of births for 2004. The records are
      weighted to independent control counts of all births received in State vital
      statistics offices in 2004. Comparisons are made with 2003 data. RESULTS: The
      crude birth rate declined 1 percent to 14.0 births per 1,000 population. The
      fertility rate, however, rose slightly to 66.3 births per 1,000 women aged 15-44
      years. Birth rates for teenagers 15-19 years declined modestly. The rate in 2004
      was 41.2 births per 1,000 females aged 15-19 years, 1 percent lower than in 2003.
      Rates declined 1 percent each for teenagers 15-17 and 18-19 years. The rate for
      10-14 year-olds increased slightly. The birth rate for women aged 20-24 years
      declined 1 percent to 101.8, a record low for the Nation. The rate for women aged
      25-29 years remained essentially unchanged at 115.5 per 1,000. The birth rate for
      women aged 30-34 years rose less than 1 percent to 95.5 per 1,000, whereas the
      rates for women aged 35-39 and 40-44 years increased 3 to 4 percent each. The
      rate for women aged 45-49 years rose to 0.6 per 1,000. Childbearing by unmarried
      women rose to a record high of almost 1.5 million births in 2004, a 4-percent
      increase from 2003. The proportion of all births to unmarried women increased to
      35.7 percent. Smoking during pregnancy declined slightly in 2004, to 10.2 percent
      of mothers in the 40-State reporting area. There was no improvement in timely
      receipt of prenatal care. In 2004, 83.9 percent of mothers in the 41-State
      reporting area began care in the first trimester. A record high cesarean delivery
      rate was reported in 2004, at 29.1 percent of all births, a 6-percent increase
      from 2003. The primary cesarean rate rose 8 percent, whereas the rate of vaginal
      birth after cesarean delivery declined 13 percent. Preterm and LBW rates each
      increased in 2004. More than 500,000 infants were born preterm, a rate of 12.5
      percent. The LBW rate increased to 8.1 percent.

PMID- 16450553
TI  - Autonomous regulation in nursing.

PMID- 16450554
TI  - Facilitation as a teaching strategy: the experiences of nursing students.
AB  - This study was undertaken to assess the needs/problems of students of nursing
      regarding facilitation as a teaching/learning method. Facilitation as a teaching
      and learning strategy was uncommon and innovative in nature and presented a
      challenge to the students as it was a new way of learning. Focus group interviews
      were conducted. The sample study consisted of eight (8) groups of learners from
      four universities engaged in this curriculum. To answer the research question a
      qualitative, exploratory, descriptive design was used and the students were
      selected purposively. Data analysis using transcribed focus interviews, was based
      on the combined approaches of Tesch (1990) in Cresswell (1994:153-155) and the
      basic steps of Giorgi (1970) as quoted by Omery (1983:49-63). The themes
      identified were about the experiences of the facilitation process and problems
      with the facilitators. All the students experienced the facilitation of learning
      negatively in the beginning but became more positive later when they adapted to
      this method of learning.

PMID- 16450555
TI  - Dietary intake of pregnant women and their infants in a poor black South African
      community.
AB  - The aims of this study were (i) to determine the dietary intake of women in a
      poor rural area during pregnancy and lactation, and (ii) to determine the
      nutritional status and dietary intake of their infants at age 6 months. We
      recruited 46 women, below 40 years old, in their 2nd trimester of pregnancy. The
      subjects were living in a rural area of Limpopo Province. Their heights and
      weights were recorded, as were their diets during pregnancy and for the first 6
      months after delivery. We also recorded weights, lengths, and dietary intake of
      the infants at 3 and 6 months after birth. The subjects were living in severe
      poverty: none had running water and almost all did their cooking over an open
      fire. None of the subjects smoked and only one consumed alcohol. The diets of the
      subjects consisted mainly of maize, brown bread, sweetened beverages (cold drink
      and tea), and small amounts of vegetables and chicken. The diets were adequate in
      protein but were marginal in energy and in dietary fibre, and may be deficient in
      numerous micronutrients, particularly calcium, iron, zinc, niacin, folate, and
      vitamins A, C, E, and B6. This was seen during pregnancy and lactation. Blood
      analysis 6 months after birth revealed normal levels of vitamins A and E and an
      absence of anaemia. Body mass index (BMI) of the women was 23.9 +/- 5.3 kg/m2
      (mean +/- SD) when measured 6 months after birth. Those above 25 years old had a
      higher BMI than did younger subjects (25.5 vs. 22.2; p = 0.028). Overall, 24%
      were overweight (BMI 25-30) while 9% were obese (BMI > 30). Most infants (93%)
      were breastfed for at least 6 months but exclusive breastfeeding was only done by
      65% of mothers. One-third of breastfed infants also received formula. The use of
      formula while breastfeeding was twice as common among mothers aged above 25 years
      (46% vs. 23%). Early introduction of solid foods was very common in this group.
      Younger mothers introduced solids in the first month (51%) more often compared
      with older mothers who tended to introduce solids at 2-3 months (64%). The most
      common solid food given was maize meal porridge (by 78% of all mothers). Mean BMI
      was low at birth (< 15), but this reached a normal value by 6 months. A
      significant fraction of the infants was underweight or short (i.e., stunted),
      based on being below the 3rd percentile compared with NCHS standards. Underweight
      was short length in girls. This study found that pregnant and lactating women had
      diets low in energy and micronutrients as reflected by the high prevalence of
      underweight at birth. Most infants were exclusively breastfed, but the benefit of
      this was offset by the early introduction of solid foods having a low energy and
      nutrient density. By 6 months, the prevalence of stunting had more than doubled.

PMID- 16450556
TI  - The patient relationship and therapeutic techniques of the South Sotho
      traditional healer.
AB  - Until 1996 the practice of traditional healers was outlawed in South Africa and
      not afforded a legal position in the community of health care providers. In 1978
      the World Health Organization (WHO) identified traditional healers as those
      people forming an essential core of primary health care workers for rural people
      in the Third World Countries. However in 1994 the new South African government
      identified traditional healers as forming an essential element of primary health
      care workers. It is estimated that 80% of the black population uses traditional
      medicine because it is deeply rooted in their culture, which is linked to their
      religion. The traditional healer shares with the patient a world view which is
      completely alien to biomedical personnel. Therapeutic techniques typically used
      in traditional healing conflict with the therapeutic techniques used in
      biomedicine. The patients' perceptions of traditional healing, their needs and
      expectations, may be the driving force behind their continuous persistence to
      consult a traditional healer, even after these patients may have sought the
      therapeutic techniques of biomedical personnel. The operation of both systems in
      the same society creates a problem to both providers and recipients of health
      care. Confusion then arises and the consumer consequently chooses the services
      closer to her. The researcher aimed at investigating the characteristics of the
      relationship between the traditional healers and the patients, explored the
      therapeutic techniques that are used in the South Sotho traditional healing
      process, and investigated the views of both the traditional healers and the
      patients about the South -Sotho traditional healing process, to facilitate
      incorporation of the traditional healers in the National Health Care Delivery
      System. A qualitative research design was followed. Participants were identified
      by means of a non-probable, purposive voluntary sample. Data was collected by
      means of a video camera and semi-structured interviews with the six traditional
      healers and twelve patients, as well as by taking field notes after each session.
      Data analysis was achieved by means of using a checklist for the video
      recordings, and decoding was done for the interviews. A co-coder and the
      researcher analysed the data independently, after which three consensus
      discussions took place to finalise the analysed data. The researcher made
      conclusions, identified shortcomings, and made recommendations for application to
      nursing education, nursing research and nursing practice. The recommendations for
      nursing are reflected in the form of guidelines for the incorporation of the
      traditional healers in the National Health Care Delivery System.

PMID- 16450557
TI  - Accompaniment needs of nursing students related to the dying patient.
AB  - Nurse educators are responsible for accompanying students towards becoming
      capable, competent professional nurses who are a credit to themselves, their
      patients, colleagues and profession. Student nurses need, therefore, to be taught
      to render comprehensive nursing care to patients in all stages of their lives,
      including when they are dying. Being confronted with human suffering and death is
      challenging and traumatic. Those exposed to such events on a daily basis need to
      have a solid foundation of self preservation to see past the pain of suffering
      and to bring light and hope to those in need. A young student nurse will only
      experience positive growth and development in these circumstances if she is also
      cared for and guided with understanding. The researcher utilized a qualitative,
      explorative, descriptive and contextual design based on the phenomenological
      approach to enquiry. The following question was asked at the beginning of each
      unstructured phenomenological interview: "How was if for you to care for a dying
      or deceased patient?" The central theme identified that student nurses experience
      turmoil in their different relationships in their accompaniment of the dying
      patient. Guidelines based on the central theme and sub-themes that emerged from
      raw data, as well as literature, are offered as strategies to promote/enhance
      optimal accompaniment of student nurses caring for the dying patient.

PMID- 16450558
TI  - Maternal anthropometry and pregnancy outcomes: a proposal for the monitoring of
      pregnancy weight gain in outpatient clinics in South Africa.
AB  - The aim of this review was to develop a framework for the monitoring of pregnancy
      weight gain in South African outpatient clinics. Studies showed that intrauterine
      malnutrition have more serious consequences for children than postnatal
      malnutrition. Undernutrition, as well as overnutrition during pregnancy, was
      associated with adverse pregnancy outcomes. The IOM published recommended weight
      gains by pre-pregnancy body mass index (BMI). Wasting in pregnant women can be
      defined as a mid-upperarm circumference (MUAC) < 22cm. Low prepregnancy BMI is
      considered a risk factor for preterm birth and intra-uterine growth retardation.
      Pregnant women in developing countries start to attend antenatal clinics late in
      pregnancy, so that prepregnancy BMI may be unknown and antenatal care can be
      based on pregnancy weight gain only. A framework is proposed that identifies the
      critical points for action during pregnancy to improve birth outcomes. Health
      care providers should measure height, weight and MUAC and try to classify
      pregnant women according to weight status, set weight gain goals and monitor
      gestational weight gain between follow-up visits. Women with short stature (<
      145cm), low body weight (< 45kg), and/or MUAC < 22cm are considered to be at risk
      of adverse pregnancy outcomes. Weekly weight gains should range from 0.3kg for
      overweight women to 0.5kg or more for underweight women from the second
      trimester. Genetic background, age, general health, HIV and educational status,
      cigarette smoking, past nutritional status of the mother, parity, multiple
      pregnancies, climate, socioeconomic conditions and the availability of health
      services should be adjusted for in statistical analyses.

PMID- 16450559
TI  - The development of the model for recognition of prior learning for nurses in
      South Africa: development of RPL guidelines by the policy makers and stakeholders
      of nursing.
AB  - The National Qualifications Framework (NQF) was established to address the
      compartmentalization of education and training, the absence of norms and
      standards and the need for international recognition. According to the South
      African Qualifications Authority (1996),this framework was aimed at developing a
      comprehensive qualifications structure and an integrated approach to education
      and training in the country (NCHE, 1996:46). Educational institutions, including
      those for nursing, were challenged with a view to rethink the whole culture of
      teaching and learning and was counted as knowledge. The major principle of the
      NQF was the Recognition of Prior Learning (RPL), which had to be persued across
      all sectors (Musker, 1998: 8). RPL was seen as a means to widen access into
      learning programs for those who had been historically denied this. The challenge
      for educational institutions was how to ensure that RPL systems once implemented
      did not compromise academic standards. Research into methodologies to implement
      the NF in the absence of mechanisms was then essential. The purpose of the study
      was to develop and test a RPL model for nurses in South Africa. The study adopted
      a multi phase decisions-oriented evaluation research design. Stuffelbeam's
      educational evaluation model was used to guide data collection and analysis. The
      research questions were incorporated under the different phases of evaluation.
      The model was development at six levels: level one was at the policy makers
      level; level two was at the stakeholders; levels three to six were at
      institutional level where three institutions participated at pilot site for the
      RPL model development. These levels are presented as tiers in the figure 1. This
      article present the results of the model development at the first two levels,
      which according to Stuffelbeam's model is the context evaluation for boundary
      setting. Part two will present the model development at institutional level,
      involving the input and process evaluation and depicted as tiers three, and four.

PMID- 16450560
TI  - An assessment by nurses and mothers of a 'Road-to-Health' Book in the Western
      Cape.
AB  - OBJECTIVES: To evaluate English, Afrikaans, and Xhosa mother-retained 'Road-to
      Health Book' (RTH book) for children, and an electronic calculator. DESIGN:
      Researchers D Harrison (DH) and H Harker (HH) informed clinic staff about the
      contents and significance of the RTH book. They requested nurses to use this book
      in conjunction with the Road-to-Health Card and to issue and explain its use to
      every visiting client. The use of an electronic calculator that plotted
      horizontal centile and Z-score charts was demonstrated and explained. To
      determine the relevance of the book and the electronic calculator, nurses
      involved in the study for 6 months were given three standardised descriptive
      questionnaires with 'yes', 'no' and 'don't know' responses. Clients were traced
      and interviewed by the researchers after 6 - 12 months to obtain their views on
      the book. SETTING: Clinics that provided children with healthcare in 24 locations
      in the Western Cape Province participated in the study. The children lived in
      informal settlements, in low-, middle- and high-income residential areas, and on
      farms in the Cape Town, Stellenbosch, and Paarl regions. SUBJECTS: One hundred
      and fourteen nurses were enrolled in the study as well as 581 clients to whom the
      RTH book was issued. OUTCOME MEASURES: The use of and comments on the RTH book by
      nurses and clients were based on analysis of the questionnaires. RESULTS: The
      majority of nurses (81.6%) and clients (96%) found the RTH book useful. The
      horizontal and Z-score growth charts and electronic calculator were less
      acceptable because their use was time-consuming and less well understood.
      CONCLUSION: The RTH book with appropriate modifications should be issued to
      clients in place of the current Road-to-Health card and educational material.

PMID- 16450561
TI  - Experiences of final year nursing students in their preparedness to become
      registered nurses.
AB  - The objectives of this study were: firstly, to explore and describe the
      experiences of final year nursing students relating to how they experience their
      preparedness to fulfil the role of professional nurse; secondly, to explore and
      describe the experiences of novice professional nurses in the role of
      professional nurse; finally, to generate a model which will assist the final year
      nursing student to become a professional nurse. A theory-generative, qualitative,
      explorative, descriptive and contextual research design was utilized to reach the
      objectives of the study. Results indicated that final year nursing students
      experience a lack of confidence to take on the responsibilities of professional
      nursing. The results are displayed in table form and discussed in the article.
      This abstract forms part of a bigger study that addresses the professional
      maturity of the novice professional nurse for the practice of nursing.

PMID- 16450562
TI  - Factors influencing post abortion outcomes among high-risk patients in Zimbabwe.
AB  - Post abortion complications remain one of the major causes of mortality among
      women of child bearing age in Zimbabwe. Based on this problem, factors associated
      with mortalities due to abortion were investigated with the aim of improving post
      abortion outcomes for Zimbabwe's women, and possibly also for women of other
      African countries. Cases and controls were selected from 4895 post abortion
      records to conduct a retrospective case-control study. Significant risk factors
      identified for reducing mortalities due to post abortion complications included
      the administration of oxytocic drugs and evacuation of the uterus whilst anaemia
      and sepsis apparently reduced these women's chances of survival. Women who died
      (cases) from post abortion complications apparently received better reported
      quantitative care than controls. Recommendations based on this research report
      include improved education of health care workers and enhanced in-service
      training, regular audits of patients' records and changed policies for managing
      these conditions more effectively in Zimbabwe.

PMID- 16450564
TI  - Corticosteroid pharmacokinetic/pharmacodynamic parameters and their relationship
      to safety and efficacy.
AB  - All inhaled corticosteroids (ICSs) exert their pharmacologic effects through the
      same mechanism. This review examines pharmacokinetic profiles of ICSs to explain
      the variations in efficacy and adverse effects seen with these agents and
      identify ideal properties for an optimal ICS. For optimum efficacy and safety,
      the ideal ICS would have high pulmonary bioavailability with pulmonary activation
      for targeted delivery, negligible oral bioavailability, high plasma protein
      binding, rapid systemic clearance, and sustained pulmonary residence to permit
      once-daily dosing.

PMID- 16450563
TI  - Farm worker injuries on Western Cape fruit farms: the role of the lay health
      worker.
AB  - AIM AND METHOD: An exploratory and descriptive study to obtain basic data on the
      extent, nature, sources and severity of injuries sustained on fruit farms was
      conducted. The possibility of utilizing lay health workers (LHWs) on farms to
      document routine information on injuries was also investigated. Descriptive
      information of all injuries occurring on selected farms, both occupational and
      other, needing some form of treatment, were documented over a one-year period
      from June 1999 to May 2000. A purposive non-probability sampling method was used.
      Forty-eight fruit farms with a history of trained LHWs were purposefully
      selected. Injuries were documented using a one-page questionnaire. RESULTS: A
      total of 500 injuries were recorded, giving an average of 10.4 injuries per farm
      per year. Half of these injuries were work-related. Workers aged 20-39 were most
      at risk. Injuries sustained were related to routine activities of fruit farming,
      occurred mostly in the orchards and involved cuts, bruises and abrasions to the
      hands, including the fingers, and the eyes. Most of the non-work related injuries
      occurred in and around the home. A third of these injuries were sustained by
      persons < 20. A large percentage of the non-work related injuries were violence-
      and alcohol related. Most of the injuries required basic primary health care that
      could be managed by the LHW. Injury severity caused people to take time off for
      one third of the cases. CONCLUSION: A relatively high occupational injury rate in
      comparison to high-income countries. Occupational Health and Safety legislation
      needs to be institutionalized and adhered to. Alcohol and violence on farms is a
      serious public health problem. LHWs could potentially play an important role in
      documenting injury data.

PMID- 16450565
TI  - The relationships of rhinitis and asthma.
AB  - Rhinitis and asthma are common airway conditions; however, recent data suggest
      that they both can be clinical manifestations of a systemic inflammatory process
      within the respiratory tract. The link between these two airway disorders has
      been called the "integrated airway hypothesis." Several epidemiological studies
      have established an association between rhinitis and asthma, and approximately 19
      38% of patients with allergic rhinitis have coexistent asthma. Additionally, an
      understanding of the biology of the two airway disorders suggests that systemic
      inflammation after local allergen challenge links the upper and lower airways.
      More recently, data from clinical studies in patients with rhinitis and
      coexistent asthma have highlighted that an improved control of nasal symptoms
      frequently results in improved asthma symptom scores. To clarify the
      relationships between upper and lower airway disorders and to establish the
      potential benefits of an integrated airways management approach, additional
      studies are warranted.

PMID- 16450566
TI  - Asthma, sports, and death.
AB  - The impact of asthma on the general population has been described in detail in
      medical literature. However, asthma also has a significant impact on the
      pediatric and adult athlete. This is rarely reported in either the lay press or
      the medical literature. In 2003, Becker and coworkers conducted a retrospective
      analysis of the incidence of asthma as a direct cause of death in competitive
      athletes across the United States between 1993 and 2000. They sought to raise
      awareness that severe asthma exacerbations and even death can occur during sports
      from asthma in athletes, while still supporting the concept of maximal
      participation in sporting activities. To their knowledge, this remains the only
      published study looking specifically at this issue. Fortunately, fatal asthma
      events are infrequent in either the adult or the pediatric populations. Those
      rare cases involving athletes are commonly highlighted in the lay press when they
      do occur, e.g., when the victim is a college football player such as Rashidi
      Wheeler. Wheeler died of a fatal asthma exacerbation on August 3, 2002, during a
      conditioning drill as a member of the Northwestern University football team.
      Although he was known to have chronic asthma with no obvious barriers to health
      care, he nevertheless succumbed to his condition. Here, we report a similar,
      although less well-known, case of an adolescent who died as a direct result of an
      asthma exacerbation during a high school physical education class. We also offer
      a brief review of the literature regarding morbidity and mortality in athletes.

PMID- 16450567
TI  - Differential diagnosis of chronic cough.
AB  - Coughing that lasts >3 weeks is generally considered chronic. The causes of
      chronic cough are many. Most often, chronic cough is due to postnasal drainage,
      asthma, and/or gastroesophageal disease. However, other causes such as
      laryngopharyngeal reflux, vocal cord dysfunction, occult sinusitis, pertussis,
      and angiotensin-converting enzyme inhibitor should be considered. Even rarer
      entities will be discussed as well as some of the pathophysiology associated with
      the cough reflex.

PMID- 16450568
TI  - Conifer pollen sensitivity in western New York: cedar pollens.
AB  - Cedar pollens might be significant allergens in areas where they have not been so
      considered but are prevalent. Eastern red cedar (Juniperus virginiana) and white
      cedar (Thuja occidentalis, American arbor vitae) are common plants in western New
      York. We analyzed skin test results from 158 patients with asthma, rhinitis, or
      both; 102 had positive skin tests to at least one pollen. Among those, 52
      patients (51%) had positive skin tests to at least one of the cedar pollens.
      Patients sensitive on skin testing to cedar pollen were strongly likely (p <
      0.0001) to be sensitive to deciduous tree, grass, or ragweed pollen. Sensitivity
      on skin testing to indigenous cedar pollens is common in our area of western New
      York and therefore could be clinically significant.

PMID- 16450569
TI  - Modern prevalence of insect sensitization in rural asthma and allergic rhinitis
      patients.
AB  - Inhalant allergy to insects other than cockroaches and dust mites was described
      in the 1950s, but little attention has been paid to these findings. Sensitization
      rates for many allergens have increased since then. In this rural population, we
      describe the current prevalence of sensitization to commonly found insects. We
      evaluated 200 patients (38 adults and 162 children), for immunoglobulin E (IgE)
      mediated sensitization to the caddis fly, mayfly, moth, carpenter ant, and
      housefly using the prick technique and commercially available whole-body
      extracts. All had symptoms consistent with asthma and/or allergic rhinitis. They
      also were tested to indoor and outdoor aeroantigens. Of the 200 patients, 60
      patients (30%) tested positive to at least one of the five insects. The most
      prevalent positive skin test was to the mayfly (37/60), followed by the housefly
      (36/60), caddis fly (27/60), moth (14/60), and ant (10/60). Of the 60 patients
      positive for insects, 35 patients (58%) also tested positive to at least one
      species of mite, 36 patients (60%) tested positive to the cockroach. Twelve of
      the 60 patients (20%) with positive insect testing did not react to either
      cockroaches or mites. In our patients, the immunoglobulin E-mediated
      sensitization rate to insects excluding cockroaches is 30%. Many patients also
      were sensitized to mites and/or cockroaches. These insects are all present in the
      indoor/outdoor environment of this rural population. Cross-reactivity with mites
      and cockroaches (insect panallergy) may partially explain our results. The
      presence of skin test sensitivity in the absence of cockroach or mite allergy
      suggests possible true insect sensitization.

PMID- 16450570
TI  - Anaphylaxis and epinephrine prescribing patterns in a military hospital:
      underutilization of the intramuscular route.
AB  - Epinephrine is the only definitive treatment of anaphylaxis, and recent evidence
      suggests that the intramuscular route has superior pharmacokinetics to
      subcutaneous administration. There is little data regarding what route is
      commonly used in clinical practice. The objective of this article is to determine
      the rate of epinephrine use in cases of anaphylaxis and route of administration
      utilized. A retrospective review was made of 220 medical records with the primary
      diagnosis of urticaria, angioedema, or anaphylaxis over a 28-month period at a
      military medical center. Twenty-four cases of anaphylaxis identified in the
      records. Demographics, along with signs and symptoms of those experiencing
      anaphylaxis, were similar to other published reports. Epinephrine was given in
      only 50% of cases and largely by the subcutaneous route. No intramuscular
      epinephrine was administered. H1 blockers and steroids were the most commonly
      administered treatments. H2 blockers were given at the same rate as epinephrine.
      An autoinjector was prescribed in 29% of cases with instruction on its use
      documented in 13%. An allergy referral was made in 29% of cases. Greater
      educational efforts and collaboration are needed between the allergy community
      and other providers regarding the importance of administering epinephrine
      intramuscularly, prescribing autoinjectors, and referring to an allergist in
      cases of anaphylaxis.

PMID- 16450571
TI  - The relationship between delta-forced vital capacity (percent fall in forced
      vital capacity at the PC20 dose of methacholine) and the maximal airway response
      in patients who have mild asthma.
AB  - Airway hypersensitivity is routinely evaluated by measuring the concentration
      (PC20) of inhaled methacholine or histamine that causes a 20% fall in forced
      expiratory volume in 1 second (FEV1). It has been suggested that a percentage
      fall in forced vital capacity (FVC) measured at the PC20 dose of inhaled agonist
      (deltaFVC) is a potentially useful clinical measure in patients who have asthma
      because it provides indirect information about gas trapping and therefore the
      maximal airway response. The relationships between serum eosinophil cationic
      protein (ECP) levels and the maximal airway response or deltaFVC are largely
      unknown. The aims of this study were to determine whether deltaFVC is correlated
      with the degree of maximal airway response and to examine the relationships
      between serum ECP and deltaFVC or maximal airway response in patients who have
      mild asthma. Fifty-eight patients with mild asthma underwent high-dose
      methacholine challenge testing. The PC20, maximal airway response, and deltaFVC
      were measured on the methacholine dose-response curves. Serum ECP levels also
      were determined. Subjects without a maximal response plateau (n = 33) had a
      significantly higher level of deltaFVC (17.9 +/- 4.1%) than subjects with a
      plateau (n = 25; 14.9 +/- 4.8%). A significant correlation was found between
      deltaFVC and the level of maximal response plateau (r = 0.446; p = 0.026). Not
      only methacholine PC20 but also maximal airway response or deltaFVC had no
      relationships with serum ECP levels. Our results suggest that deltaFVC can be
      used as a surrogate marker of maximal airway response in patients who have mild
      asthma and that neither maximal airway response nor deltaFVC reflects blood
      eosinophil activation any more than methacholine PC20.

PMID- 16450572
TI  - Immune defects in subjects with dysmorphic disorders.
AB  - Patients with dysmorphic disorders seem to have frequent respiratory infections
      that may be attributed to associated anatomic or neurological abnormalities, but
      immune defects may contribute to their susceptibility to infections. We screened
      subjects with dysmorphic conditions for major hematologic, B-cell and T-cell
      defects. We studied 84 subjects with dysmorphic disorders: 29 with chromosomal
      disorders, 27 with single gene disorders, and 28 with unclassified dysmorphic
      disorders. They were evaluated by physical examination; medical history
      suggestive of possible immune deficiency; complete blood count; serum
      immunoglobulin G (IgG), IgA, and IgM levels; and lymphocyte subsets. Low
      laboratory values (less than fifth percentile for age) were detected in 54.8%;
      was highest in the chromosomal disorder group (79.3%) followed by the single gene
      disorder group (55.6%) and was lowest in the unclassified dysmorphic disorder
      group (28.6%). The most common low values were in the CD19 and CD16/56 lymphocyte
      subpopulations followed by IgG and IgA levels. None of the subjects had
      neutropenia or thrombocytopenia. History of significant recurrent infections was
      noted in five subjects, all of whom had abnormal laboratory values. The highest
      frequency of abnormal laboratory values was in Down syndrome followed by Turner
      syndrome and chromosome deletions. We concluded that patients with dysmorphic
      disorders, particularly those with chromosomal disorders, have a high frequency
      of various B-cell and T-cell defects that may be contributing to their
      susceptibility to infection. Studies are needed to further delineate the
      immunologic defects in that population and to investigate a possible genetic
      basis at the molecular level.

PMID- 16450573
TI  - An approach of immunoneurological aspects in nasal allergic late phase.
AB  - This examination is an approach of the allergic early phase reaction (EPR) and
      late-phase reaction (LPR) via quality of life (QoL), acoustic rhinometry, and
      eosinophilic cationic protein (ECP), interleukin (IL)-5, and leukotriene C4
      (LTC4). Results are discussed under consideration of a possible neurological
      participation in the occurrence and persistence of the allergic inflammatory
      process. Thirteen patients suffering from seasonal allergic rhinitis were
      challenged intranasally by their specific allergen. In a time window of 8 hours
      after provocation, patients completed QoL questionnaires, and underwent acoustic
      rhinometry. Nasal secretions were analyzed for total protein, ECP, IL-5, and LTC4
      The need to sneeze and a runny nose were the strongest symptoms during the EPR
      and LPR. Restriction of overall QoL persisted much longer than any other symptom.
      Evaluation of acoustic rhinometry revealed an EPR in 100% and a LPR in 92%. The
      EPR was marked by increases in volume of nasal secretions, total protein, and
      elevations in LTC4. Allergic LPR was marked by increases in nasal secretions,
      total protein, ECP, IL-5, and LTC4. Both the need to sneeze as strongest and
      announcing symptom of the allergic LPR and the persisting restriction in overall
      QoL seem to propose a possible neurological participation in the development of
      the allergic late-phase inflammation and consequent hyperresponsiveness of the
      nasal mucosa. In addition, the persistence and enhancement of the nasal cycle
      during the allergic LPR can be interpreted in favor of a hypothetical activation
      of the autonomous nervous system. LTC4 enters this discussion as a promising link
      at the immunoneurological interface.

PMID- 16450574
TI  - Efficacy and safety of desloratadine/pseudoephedrine tablet, 2.5/120 mg two times
      a day, versus individual components in the treatment of patients with seasonal
      allergic rhinitis.
AB  - Although antihistamines are highly effective in alleviating many symptoms
      associated with seasonal allergic rhinitis (SAR), relief from nasal congestion is
      variable. The efficacy of desloratadine, an effective antihistamine, in
      combination with pseudoephedrine, a potent nasal decongestant, was evaluated to
      determine whether combination therapy was more effective than individual
      component therapy in reducing nasal congestion, as well as other SAR symptoms.
      This multicenter, randomized, double-blind, three-arm study included 650 patients
      with SAR. For 2 weeks, patients were administered a combination tablet of
      desloratadine plus pseudoephedrine (desloratadine/pseudoephedrine, 2.5/120 mg)
      twice per day (b.i.d.), desloratadine (5 mg) once per day, or pseudoephedrine
      (120 mg) b.i.d. Patients assessed the severity of their SAR symptoms twice daily
      on symptom diary cards. The primary variable-change from baseline in the
      reflective A.M./P.M. total symptom score, excluding nasal congestion-was
      significantly superior (-6.7) compared with desloratadine (-5.4) or
      pseudoephedrine (-5.3) alone (p < or = 0.001 versus either group). Secondary
      efficacy variables including total symptom scores (plus congestion), total nasal
      symptom scores, and total nonnasal symptom scores were significantly reduced
      after desloratadine/pseudoephedrine therapy compared with the individual
      components. The most frequently reported adverse events were insomnia, headache,
      and dry mouth. Desloratadine/pseudoephedrine, 2.5/120 mg b.i.d., therapy was more
      effective in reducing total symptom scores of SAR, including nasal congestion,
      than were the individual components. These results support the use of this
      combination therapy over desloratadine or pseudoephedrine alone.

PMID- 16450575
TI  - Prevalence and risk factors for childhood asthma in Zonguldak, Turkey.
AB  - Prevalence of asthma and other allergic diseases varies between different regions
      throughout the world. The aim of this study was to determine the prevalence of
      asthma and allergies and some risk factors for asthma in schoolchildren, aged
      between 6 and 16 years old, in Zonguldak, Turkey. We prepared 1500 questionnaires
      according to the International Study of Asthma and Allergies in Childhood
      criteria and distributed them in schools, to be completed at home by parents.
      Appropriately completed 1349 questionnaires, including complementary questions
      for risk factors, were taken into consideration. Data for air-pollutant levels of
      sulfurdioxide (SO2) and total suspended particles were obtained also. The
      prevalence of current wheezing symptoms was 9.6% in children aged between 13 and
      16 years old and 11.2% in the total sample. In terms of physician-diagnosed
      asthma, allergic rhinitis, and eczema, the prevalences were 4.9, 37.7, and 13.2%,
      respectively. A family history of allergy, diagnosis, or symptoms of allergic
      rhinitis and bronchitis (age range, 6-9 years) and male gender were found to be
      significant predictors for asthma symptoms with adjusted odds ratios of 2.089,
      0.336, 4.707, 1.652, and 0.599, respectively. Strongly positive correlation
      between number of symptomatic asthmatic patients and air pollution levels for SO2
      (r = 0.864; p = 0.001) and total suspended particles (r = 0.891; p = 0.001) were
      observed also. The prevalence of asthma is high in Zonguldak, Turkey, and there
      is a strong correlation between air pollution and asthma symptoms. Allergy in the
      first-degree relatives, diagnosis of bronchitis and allergic rhinitis, age, and
      male gender are more important than the other factors in predicting asthma.

PMID- 16450576
TI  - The prevalence of asthma, allergic rhinitis, and atopy in Antalya, Turkey.
AB  - Bronchial asthma is a common chronic inflammatory disorder of the airways that
      causes serious morbidity and mortality. The prevalence of the disorder has been
      increasing, especially in developed countries. The population-based asthma
      prevalence studies provide data from Ankara, Istanbul, Gaziantep, Trabzon,
      Izmnir, and Kayseri in our country and asthma prevalence ranges between 1.4 and
      3%. However, the prevalence of adult asthma in our city was not known. We aimed
      to determine the prevalence of asthma, allergic rhinitis, and atopy in the adult
      population of Antalya and compare the data with other countries and other regions
      of our country. The European Commission Respiratory Health Survey, the first
      study to assess the geographical variation in asthma and allergic diseases,
      provided comparable data from 22 countries and 140,000 individuals. Therefore,
      the European Commission Respiratory Health Survey protocol was preferred in our
      study. The first stage consisted of 1000 subjects; of these 1000 subjects, 200
      subjects were randomly selected for the second stage. The response rates were
      99.5 and 55.4% for stages I and II, respectively. The current prevalence of
      asthma, allergic rhinitis, and atopy in Antalya was 9.4, 27.7, and 31.1%,
      respectively. The most prevalent type of sensitization was mite allergy detected
      in 31 (20.9%) subjects. Sensitization to more than one allergen was frequent in
      subjects with asthma and allergic rhinitis. Bronchial asthma, allergic rhinitis,
      and atopy are frequent in our city and when compared with previous studies
      performed in Turkey, the highest results were in Antalya.

PMID- 16450578
TI  - Resolution of chronic urticaria and angioedema with thyroxine.
AB  - Chronic urticaria (CU) is a clinically perplexing condition that not only can
      compromise the patient's quality of life but also frequently fails to respond
      satisfactorily to treatment with antiallergy medications such as antihistamines.
      For a considerable time, CU has been considered a disease of unknown etiology,
      but in recent years, a wide variety of causes and mechanisms have been suggested.
      An autoimmune basis linking the role of autoantibodies to thyroid tissue(s) in
      the pathogenesis of CU has been reported in a limited number of patients with the
      condition. Once diagnosed, most such cases respond well to the addition of
      thyroxine to the therapeutic regimen. Nevertheless, the evaluation of CU rarely
      includes consideration of the causal relationship of autoimmune thyroiditis in CU
      and inclusion of thyroid autoantibodies in the diagnostic regimen. This case
      report documents the dramatic improvement of a patient with CU after initiation
      of thyroxine therapy.

PMID- 16450577
TI  - Is there an increase in the prevalence of allergic diseases among schoolchildren
      from the Aegean region of Turkey?
AB  - The prevalence of asthma, allergic rhinitis, allergic conjunctivitis, and
      allergic skin disorders (urticaria and atopic dermatitis) was investigated
      between the years 1993 and 1994 in the Aegean region of Turkey and was found to
      be 3.8, 4.6, 12.6, and 19.4%, respectively (Tanac R, Kurugol Z, Demir E, et al.,
      Cocuk Sagligi ve Hast Derg 39:77-85, 1996). The aim of the present study was to
      determine whether there is a change in the prevalence of allergic diseases in the
      Aegean region in the last 8 years, based on the comparison of the results using
      the same method applied in the study mentioned above. Three thousand three
      hundred seventy children (48.6% male participants and 51.4% female participants)
      between the ages of 5 and 18 years (mean age, 11.55 +/- 3.34 years) were enrolled
      in the study. The participants were randomly chosen among children attending
      primary schools in the cities of the Aegean region. The children completed a
      questionnaire; and physical examinations, serum-specific immunoglobulin E
      antibody levels, and peak expiratory flow measurements were done for each of
      them. Of the children, 21.2% were found to have at least one attack of wheezing
      whereas the prevalence of asthma was 6.4%. The prevalence of allergic rhinitis,
      allergic conjunctivitis, and allergic skin disorders (urticaria and atopic
      dermatitis) were found to be 13.6, 13.2, and 23.7%, respectively. The increase of
      prevalence for asthma was 2.6%, for allergic rhinitis was 9%, and for allergic
      conjunctivitis was 0.6%. These data show that the prevalence of allergic
      diseases, especially respiratory allergy, has increased among schoolchildren from
      the Aegean region of Turkey.

PMID- 16450579
TI  - Susceptibility to mycobacterial infections due to interferon-gamma and
      interleukin-12 pathway defects.
AB  - A case of interferon-gamma (IFN-gamma)/interleukin-12 (IL-12) pathway defect is
      presented. Pathophysiology, clinical characteristics, diagnostic test, and case
      management are reviewed. Clinical Pearls and Pitfalls include: (1) A high
      probability of a defect in the IFN-gamma/IL-12 cascade exists in patients with
      disseminated or recurrent infection due to poorly pathogenic mycobacteria or
      systemic infections caused by non-typhi Salmonella species that are persistent
      and recurrent despite antibiotic therapy. (2) Although less frequent, patients
      with impaired IFN-gamma/IL-12 mediated immunity are more susceptible to
      cytomegalovirus, human herpesvirus 8, herpes simplex virus, Listeria
      monocytogenes, and Histoplasma capsulatum.

PMID- 16450580
TI  - Joint Council of Allergy, Asthma, and Immunology news: focus on practice
      management, marketing basics.

PMID- 16450581
TI  - Mechanism of trinucleotide repeats instabilities: the necessities of repeat non-B
      secondary structure formation and the roles of cellular trans-acting factors.
AB  - The mechanism underlying CAG.CTG CGG.CCG and GAA.TTC trinucleotide repeats
      expansion and contraction instabilities has not been clearly understood.
      Investigations in vitro have demonstrated that the disease causing repeats are
      capable of adopting non-B secondary structures that mediate repeats expansion.
      However, in vivo, similar observations have not been easily made so far.
      Investigations on the non-B secondary structure formation using E.coli, yeast etc
      cannot simulate the suggested repeats expansion instability. These could leave a
      space to infer a disassociation of the suggested repeats non-B secondary
      structure formation and the repeats expansion in vivo. Although longer
      trinucleotide repeats may be theoretically easier to form non-B DNA secondary
      structures in replication or in post-replication, however such non-B secondary
      structures are likely to cause repeat fragility rather than repeat expansion. In
      fact, repeat expansion as seen in patients may not necessarily require
      trinucleotide repeats to form non-B secondary structures, instead the repeat
      expansions can be produced through a RNA transcription-stimulated local repeat
      DNA replication and a subsequent DNA rearrangement.

PMID- 16450582
TI  - The admixture linkage disequilibrium and genetic linkage inference on the gradual
      admixture population.
AB  - Through the theoretical analysis of the admixture linkage disequilibrium (ALD) in
      the gradual admixture (GA) model, in which admixture occurs in every generation,
      the ALD is found to be proportional to the difference in marker allele
      frequencies, P1 - P2, between two subpopulations. Based on this property, we can
      employ a strict monotonic function (delta(ker) = delta/(P1-P2), where delta
      denotes the linkage disequilibrium (LD)) of the recombination fraction between
      the marker locus and the disease locus to infer the true genetic linkage. We
      construct a quasi likelihood ratio test (LRT) for the case-only data utilizing
      the information of unlinked markers in the human genome. The simulation results
      show that our tests can be used to fine map a disease locus. The effects of
      parameter values in the ALD mapping are also discussed.

PMID- 16450583
TI  - Genetic analysis of a family with 46,XY "female" associated with infertility.
AB  - Genetic analysis of a family with 46,XY "female" associated with infertility was
      performed using the conventional G-banding and gene mutation screening. The
      karyotypes of the two female patients were 46,XY and those of their parents were
      normal. The mutation screenings in sex-determining region Y (SRY) gene and
      androgen receptor (AR) gene were carried out. No mutation has been found in the
      whole coding sequence of SRY gene. The mutation of codon 840 CGT (arginine) to
      CAT (histidine) of AR gene led to the infertility in the patients. The patients
      showed androgen insensitivity. The clinical phenotype of theirs presented more
      deleteriously than and different from the one reported before, though they had
      the same mutation of codon 840 CGT (arginine) to CAT (histidine) of AR gene,
      which was very different from the mutation of 840 CGT (arginine) to TGT
      (cysteine) at the same codon.

PMID- 16450584
TI  - Experimental study on the suppression of human nuclear receptor hLRH-1 via a
      vector-based RNA interference.
AB  - To explore the inhibitions of human nuclear receptor hLRH-1 via RNA interference,
      siRNAs expressing vectors pShLRH-1.1 and pShLRH-1.2, and targeting hLRH-1 were
      designed and constructed. The recombinants were introduced into hepatocellular
      carcinoma cells, BEL-7402, mediated by lipofectamin. RT-PCR was carried out to
      examine the inhibition ratio of hLRH-1 expression. The same method was also
      applied to analyze the expression of farnesyl pyrophosphate synthetase (FPPS)
      gene. Our results demonstrated that after transient transfection, both pShLRH-1.1
      and pShLRH-1.2 could trigger the efficient inhibition of hLRH-1 in cultured
      cells, BEL-7402. The inhibition ratios were up to 80%. By comparing with non
      transfection and vector-transfection control, the expression of FPPS in cells
      with inhibition of hLRH-1 was up-regulated significantly. Thus, the inhibition of
      expression of hLRH-1 in cultured cells was achieved via RNA interference in this
      study. Our results also suggested that hLRH-1 acts as a negative regulator in
      FPPS expression.

PMID- 16450585
TI  - Role of svp in Drosophila pericardial cell growth.
AB  - The Drosophila dorsal vessel is a segmentally repeated linear organ, in which
      seven-up (svp) is expressed in two pairs of cardioblasts and two pairs of
      pericardial cells in each segment. Under the control of hedgehog (hh) signaling
      from the dorsal ectoderm, svp participates in diversifying cardioblast identities
      within each segment. In this experiment, the homozygous embryos of svp mutants
      exhibited an increase in cell size of Eve positive pericardial cells (EPCs) and a
      disarranged expression pattern, while the cardioblasts pattern of svp-lacZ
      expression was normal. In the meantime, the DAI muscle founders were absent in
      some segments in svp mutant embryos, and the dorsal somatic muscle patterning was
      also severely damaged in the late stage mutant embryos, suggesting that svp is
      required for the differentiation of Eve-positive pericardial cells and DA1 muscle
      founders and may have a role in EPC cell growth.

PMID- 16450586
TI  - Molecular cloning of the rice field eel Nup93 with predominant expression in
      gonad and kidney.
AB  - Nucleoporins (Nups) are important components of nuclear pore complexes (NPCs).
      NPCs control gene expression, cells proliferation and differentiation by
      mediating exchange of cellular signal molecules on both nuclear and cytoplasmic
      sides. Using subtractive screening, 3'end fragment of Nup93 from the testis cDNA
      library of the rice field eel was obtained. Full-length cDNA of the gene was
      further cloned by degenerate PCR and 5'RACE methods. Sequence analysis indicated
      that the homology of the rice field eel Nup93 were 36.5% with yeast Nic96, 94.6%
      and 90.5% with Nup93 of zebrafish and human, respectively. Phylogenetic analysis
      showed that the rice field eel Nup93 fits with Nup93 of the other fishes. Real
      time PCR result showed that expression of Nup93 in gonads and kidney were much
      higher than in other tissues, and different expression quantities among gonads of
      three sexes were also observed, suggesting that Nup93 may involve in gonad
      development.

PMID- 16450587
TI  - Generation of mouse FANCL antibody and analysis of FANCL protein expression
      profile in mouse tissues.
AB  - Fanconi anemia complementation group L (FANCL) is a novel Fanconi anemia protein,
      which mono-ubiquitinates FANCD2 as a ubiquitin E3 ligase, and plays a crucial
      role in DNA damage repair and chromosome stability maintenance. FANCL is involved
      in the proliferation of primordial germ cells (PGC) in early embryonic stages,
      and may play a role in the development of germ cells by forming a novel testis
      specific network with testis-specific proteins in the adult testis. FancL cDNA
      sequence was cloned by RT-PCR from mouse testis total RNA, and expressed in E.
      coli BL21(DE3). Rabbit FANCL polyclonal antiserum was generated using the
      recombinant protein as the antigen. To prepare an antigen column for affinity
      purification of FANCL-specific antibody, recombinant His-tagged FANCL was
      purified by Ni(2+)-charged HiTrap Chelating HP column and coupled to an NHS
      activated HiTrap column. To confirm the activity and specificity of the FANCL
      antibody, we constructed plasmid pCMV-HA/FANCL to transfect HEK 293T cells.
      Transiently expressed HA-FANCL fusion protein was analyzed by immunoblotting with
      both the FANCL antibody and HA monoclonal antibody. The antibody was used in
      Western blotting to check the expression of FANCL protein in mouse tissues. We
      found wide expression of FANCL in brain, muscle, heart, lung, liver, spleen,
      kidney, testis, ovary and uterus, indicating the functional importance of this
      novel protein.

PMID- 16450588
TI  - Expression of human BMP-2 gene in different tissues of tobacco plants.
AB  - The bone morphogenetic proteins (BMPs) are a family of growth factors that
      regulate the development of bone. BMP-2 is the most effective in the induction of
      bone tissue. A large amount of BMP-2 is needed for both bone tissue engineering
      research and clinical application. Thus, an effective way is necessary to produce
      sufficient BMP-2 protein. With the advance in plant biotechnology, transgenic
      plants have been targeted as a bioreactor to produce desired recombinant
      proteins. Here, the expression of recombinant human bmp-2 gene (rhbmp-2) was
      studied in tobacco plants using gus as a reporter gene. The difference of
      expression levels in root, stem and leaf tissues was analyzed by GUS activity
      assay, semi-quantitive RT-PCR and western blotting.The results indicated that the
      expression levels of fusion protein in root and stem tissues were significantly
      higher than those in leaf tissue. For the protein compositions in root and stem
      tissues were simpler than those in leaf tissue,this suggested that the
      purification process with root and stem tissues would potentially be easier.

PMID- 16450589
TI  - Impacts of QTL x environment interactions on genetic response to marker-assisted
      selection.
AB  - Genotype x environment (GE) interaction is a common characteristic for
      quantitative traits, and has been a subject of great concern for breeding
      programs. Simulation studies were conducted to investigate the effects of GE
      interaction on genetic response to marker-assisted selection (MAS). In our study
      we demonstrated that MAS is generally more efficient than phenotypic selection in
      the presence of GE interaction, and this trend is more pronounced for developing
      broadly adaptable varieties. The utilization of different QTL information
      dramatically influences MAS efficiency. When MAS is based on QTLs evaluated in a
      single environment, the causal QTL x environment (QE) interactions usually reduce
      general response across environments, and the reduction in the cumulative general
      response is a function of the proportion of QE interactions for the trait
      studied. However, MAS using QTL information evaluated in multiple environments
      not only yields higher general response, but the general response obtained is
      also reasonably robust to QE interactions. The total response achieved by MAS in
      a specific environment depends largely on the total heritability of traits and is
      slightly subject to relative changes between general heritability and GE
      interaction heritability. Two breeding strategies, breeding experiments conducted
      in one environment throughout and in two environments alternately, were also
      examined for the implementation of marker-based selection. It was thus concluded
      that plant breeders should be cautious to utilize QTL information from only one
      environment and execute breeding studies in another.

PMID- 16450590
TI  - Genetic analysis and physical mapping of Lk-4(t), a major gene controlling grain
      length in rice, with a BC2F2 population.
AB  - Grain size and shape are important factors affecting grain quality and yield in
      rice. Mapping, tagging and identification of their related genes can lead us to
      understand their expression pattern and mechanism network, which is to their
      control. In this study we mapped a grain length controlling gene named Lk-4(t)
      with SSR and CAPs markers by screening 800 recessive plants in a BC2F2 population
      derived from a cross of Shuhui527xXiaoli and backcrossed with Xiaoli as the donor
      parent. The distribution of grain shape parameters and thousand grain weight in
      F2 and BC2F2 population showed that backcross can diminish most unnecessary
      variations to identify the target gene more clearly. There were only two grain
      length phenotypes found among the 3 209 BC2F2 plants, long and short, indicating
      it is a qualitative trait. The frequency distribution for the grain length showed
      a typical segregation ratio of 3:1, suggesting that only one allele was
      responsible for the variation. By screening the recessive long grain plants with
      three CAPs markers, P1-EcoRV, P2-Sac I and P3-Mbo I, we tagged the locus on the
      arm of chromosome 3 near the centromere. Lk-4(t) was located between P1- EcoRV
      and P2-Sac I, with genetic distance of 0.90 cM and 0.50 cM from the two markers
      respectively. Mapping of the gene is a foundation for its final identification
      and function analysis.

PMID- 16450591
TI  - A non-transformation method for identifying differentially expressed genes from
      cDNA microarrays.
AB  - cDNA microarray data are subject to many sources of variation that have to be
      removed before statistical tests can be applied for identifying genes that are
      expressed differentially. Background correction, log-ratio transformation, and
      normalization, referred as the log-ratio approach, have been widely used for this
      purpose. However, there are some problems associated with this procedure. In this
      study, we proposed an alternative approach that obviates the log-ratio
      transformation step and goes directly to normalization after background
      correction. The method can estimate the "noise" effect by utilizing the
      information more effectively. Simulation studies were carried out to compare the
      feasibility and efficiency of this approach for detecting the specifically and
      differentially expressed genes under various conditions with the log-ratio
      approach. The results showed that our approach worked well and was more robust
      and powerful than the log-ratio approach.

PMID- 16450592
TI  - Shift the threshold--adenosine in tissue protection.

PMID- 16450593
TI  - Bolus injection of adenosine before cardioplegic induction improves postischemic
      global function in coronary artery bypass grafting.
AB  - BACKGROUND: Alternative strategies to optimize preexisting cardioplegia during
      myocardial preservation are currently under extensive investigation. Adenosine,
      an endogenous purine nucleoside, has been approved for its cardioprotective
      potential against ischemic-reperfusion injury. Yet, little information is
      available with respect to the use of adenosine for cardioplegic induction in
      humans. The purpose of the present study was, therefore, to assess the clinical
      relevance of intra-aortic administration of adenosine following aortic cross
      clamping with respect to the exertion of additional protection in routine
      coronary artery bypass surgery. METHODS: Thirty patients to receive elective
      coronary artery bypass grafting under cardiopulmonary bypass (CPB) were
      prospectively randomized into two study groups. Immediate after aortic cross
      clamping and just before the application of modified St. Thomas cardioplegic (20
      mL/kg), adenosine solution (250 microg/kg) was injected into the aortic root in
      the study group (n = 15), while the same amount of normal saline injection was
      administered in the control group (n = 15). Anesthesia was carried out in all
      patients in a similar fashion, and all the surgeries were performed by the same
      team. Homodynamic change, cardiac enzyme assay, and post-bypass inotropic
      supplementation were recorded throughout the study period to evaluate the extent
      of myocardial ischemic injury. RESULTS: The mean time to asystole after aortic
      cross-clamping was significantly shorter for the adenosine group compared with
      the control group (8.1 +/- 5.9 vs. 79.0 +/- 35.3 sec, respectively; P< 0.01). To
      compare with the baseline value, the mean cardiac index immediately post CPB and
      24 hours postoperatively was increased significantly for the adenosine group
      (from 2.1 +/- 0.6 to 2.6 +/- 0.6 and 3.2 +/- 0.6 L/min/m2, respectively; P <
      0.05), as contrasted with the control group (from 2.3 +/- 0.5 to 2.0 +/- 0.4 and
      2.5 +/- 0.4 L/min/m2). Further, the requirement for inotropic support after CPB
      and postoperative troponin I release were significantly less in the adenosine
      group. There appeared no adverse effects associated with adenosine
      administration. CONCLUSIONS: Immediate administration of 250 microg/kg adenosine
      via the aortic root following aortic cross-clamping could optimize the myocardial
      protective effect of conventional cardioplegia, quicken cardiac standstill, and
      offer better postoperative myocardial performance after CPB.

PMID- 16450595
TI  - Cell saver does not increase pro-inflammatory cytokine levels and expression of
      adhesive molecules in the salvaged blood of patients undergoing off-pump coronary
      artery bypass surgery.
AB  - BACKGROUND: Autotransfusion has been developed to avoid the risks of
      contaminating with infectious diseases and susceptivity to other complications of
      allogeneic blood transfusion. Previous studies have shown significant pro
      inflammatory cytokine release and complement activation during blood salvage with
      cell saver (CS) in the course of on-pump coronary artery bypass grafting (CABG)
      surgery. Because both extracorporeal pump and CS machine are possible to induce
      the adverse cytokines release, thus, in this study, we investigated the influence
      of CS alone on the levels of pro-inflammatory cytokines and the expression of
      leukocyte surface antigens in patients undergoing off-pump CABG. METHODS: Thirty
      patients proposed to undergo off-pump CABG were enrolled in this study. Five
      perioperative blood samples (peripheral blood before operation, blood in
      pericardial sac at operation, blood in the cell saver container, blood in the
      blood bag before transfusion, and peripheral blood one hour after operation) were
      obtained from each patient. The expression of activated leukocyte adhesive
      molecules (CD11b and CD18) and cytokine-inducible leukocyte-endothelial adhesive
      molecule (CD62P) were studied by flow cytometry. Enzyme-linked immunosorbent
      assay (ELISA) was conducted to determine the levels of pro-inflammatory cytokines
      including tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8.
      RESULTS: All blood samples except the one obtained one hour after operation
      showed no difference of the expression of CD11b, and CD62P and the levels of TNF
      alpha, IL-6 and IL-8 (P> 0.05). However, the expression of CD18 was decreased
      during the course of blood salvage. The peripheral blood obtained one hour after
      operation had significantly higher expression of the three tested leukocyte
      surface antigens and higher levels of three studied cytokines (P < 0.05).
      CONCLUSIONS: Our investigation indicated that the blood processing in cell saver
      alone did not increase the expression of either CD11b, CD18, or CD62P, and the
      levels of TNF-alpha, IL-6 and IL-8. The results suggest that cell saver seems not
      to significantly activate the leukocytes or cause inflammatory responses in the
      salvaged blood.

PMID- 16450594
TI  - Prophylactic versus therapeutic administration of intravenous lidocaine for
      suppression of post-extubation cough following cataract surgery: a randomized
      double blind placebo controlled clinical trial.
AB  - BACKGROUND: Post-extubation cough causes considerable patient discomfort and in
      certain surgical procedures may lead to postoperative surgical complication.
      Different drugs and techniques have been used for the prevention of post
      extubation cough with variable success rates. Prophylactic administration of
      lidocaine has been tried for the prevention of post-extubation cough with
      controversial results. No previous study has been performed to evaluate the
      therapeutic effect of intravenous lidocaine for treatment of post-extubation
      cough. This study was designed to compare the prophylactic effect of intravenous
      lidocaine with that of the therapeutic lidocaine in a sample of adult patients
      undergoing general anesthesia for cataract surgery. METHODS: The study was
      performed in two phases. In the first phase 200 adult patients were consecutively
      included in the study. They were randomly divided into two groups to receive
      either intravenous lidocaine 1 mg/kg or the same volume of normal saline as
      placebo prior to extubation. Proportions of patient with post-extubation cough
      were compared between two groups. Patients with established cough comprised the
      sample of the second phase of the study in which they randomly divided into two
      groups to receive either intravenous lidocaine 0.5 mg/kg or placebo to abort the
      coughs. Proportions of patients with successful response to lidocaine were
      compared between two groups. RESULTS: Proportions of patients with post
      extubation cough were not significantly different in two prophylactic groups as
      revealed by 19 (20.7%) in lidocaine vs. 27 (28.7%) in placebo. The efficacy of
      prophylactic lidocaine for suppression of post-extubation cough was estimated to
      be 28.1%. Proportion of patients who were successfully treated in the second
      phase of the study was significantly higher in therapeutic lidocaine group 20
      (80%) vs. 10 (38.5%) in placebo group (P = 0.003). CONCLUSIONS: The outcome of
      this study shows that prophylactic administration of lidocaine prior to tracheal
      extubation may be ineffective to prevent post-extubation cough. Based on the
      results of this study it can be recommended that post-extubation cough should be
      treated upon occurrence instead of routine prophylactic administration of
      lidocaine.

PMID- 16450596
TI  - Vigilant surgical hemostasis challenged by ketamine or hypervolemia induced
      hemodynamic stress to minimize postoperative hemorrhage in patients with
      parasagittal/or parafalcian meningiomas: an interventional study.
AB  - BACKGROUND: Prevention of postoperative intracranial hemorrhage, a serious and
      sometimes fatal complication remains the cornerstone for successful neurosurgical
      procedures. The aim of this study was to test the hypothesis whether vigilant
      rehemostasis challenged by ketamine or hypervolemia-induced hemodynamic stress
      could minimize postoperative hemorrhage. METHODS: During a five-year period
      between 1995 and 2000, in an interventional study, 37 patients having
      parasagittal or parafalcian meningiomas were randomly allocated into three
      groups. After accomplishing tumor resection and securing initial surgical
      hemostasis, the patients received one of the following treatment regimens, i.e.
      group 1, 1.5 mg/kg of ketamine given intravenously, group II, 1 liter of isotonic
      saline, and group III, as the control group receiving conventional maintenance
      fluids intraoperatively, and in all the three groups, the time consumed to
      achieve rehemostasis at the tumor bed was recorded. Twenty four hours later, a
      brain computed tomogram was obtained to evaluate the hematoma volume to tumor
      volume ratio and extent of perifocal edema and the results were recorded.
      RESULTS: The calculated hematoma volume to tumor volume ratio and the edema score
      in the ketamine group was significantly less than the control group (P < 0.05).
      These measurements were also less in the hypervolemia group compared with the
      control group although the differences were not statistically significant. The
      rehemostasis time was also significantly more in the ketamine group compared with
      the control group (P < 0.05). The postoperative hospital stay however, was
      significantly shorter in the ketamine group (P < 0.05). On the other hand the
      occurrence of postoperative edema was significantly less in the ketamine group (P
      = 0.02) compared with the control group. CONCLUSIONS: It is concluded from our
      data that, vigilant rehemostasis challenged by ketamine or hypervolemia-induced
      hemodynamic stress minimizes postoperative hemorrhage without producing
      troublesome brain edema.

PMID- 16450597
TI  - An esterification method for synthesizing prodrugs of buprenorphine.
AB  - BACKGROUND: Buprenorphine is a potent analgesic. Extending its duration of action
      would make buprenorphine more valuable for clinical use. The depot formulation
      with prodrug design is a method used to prolong the duration of a short-acting
      drug. The aim of this study was to design and develop an esterification method to
      synthesize the prodrugs of buprenorphine and also to find out the detailed
      chemical characteristics of these prodrugs. METHODS: A method of esterification
      was used. Buprenorphine prodrugs were synthesized by esterizing buprenorphine
      with various fatty acids and then purified by silica-gel column chromatography.
      The chemical structures of the prodrugs were affirmed by infrared, nuclear
      magnetic resonance and gas chromatography/mass spectrometries. RESULTS: Six ester
      type prodrugs of buprenorphine were successfully synthesized: buprenorphine
      propionate, pivalate, benzoate, valerate, enanthate, and decanoate. CONCLUSIONS:
      A proper method for esterification of buprenorphine was developed. Six ester-type
      prodrugs of buprenorphine were successfully synthesized and the detailed chemical
      characteristics of these prodrugs were put forward.

PMID- 16450598
TI  - Bilateral severe bronchial obstruction after metallic tracheal stent insertion
      for tracheal stenosis--a case report.
AB  - Metallic wire expandable stents are increasingly used to alleviate tracheal
      obstruction due to malignancies. Patients usually tolerate these stents well and
      benefit from good to excellent palliation of their symptoms. Nevertheless, some
      miserable complications have also come to our notice. We report here an
      unfortunate case in whom severe bilateral main bronchial obstruction occurred
      immediately after the insertion of a Wall-stent over the tracheal stenosis.

PMID- 16450599
TI  - Tracheo-innominate artery fistula after tracheostomy--a case report.
AB  - Tracheo-innominate artery fistula (TIF) is a rare but fatal complication after
      tracheostomy. There are no reports of survival without surgical intervention. We
      report a patient with an undiagnosed TIF who suffered massive bleeding from
      tracheostomy when we replaced the tracheostomy tube with an oral endotracheal
      tube. We emphasize the importance of keeping a high suspicion toward a possible
      TIF in any patient with bleeding from the tracheostomy site.

PMID- 16450600
TI  - Successful management of air embolism-induced ventricular fibrillation in
      orthotopic liver transplantation.
AB  - Ventricular fibrillation (VF) although less common during noncardiac surgery
      often brings about severe complication as an aftermath. We report a case of VF
      which was highly suspected to be induced by air embolism at the moment when the
      surgeon was dissecting the collateral vessels of portal vein in liver
      transplantation surgery. The outcome of this patient was excellent due to
      aggressive resuscitative measures including open-chest cardiac massage.
      Transesophageal echocardiogram (TEE) was not applied in this patient in fear of
      increased risk of esophageal varicose bleeding in a liver cirrhotic patient.
      However, some reports described the use of TEE in cirrhotic patients without
      obvious complications. In this case, venous air embolism (VAE) happened during
      the dissection of collateral vessels of the portal vein, which to our knowledge
      was ever been reported in liver transplantation surgery. The related literature
      has been reviewed and the success of the resuscitation is also herein discussed.

PMID- 16450601
TI  - Cerebral arteriovenous malformation diagnosed during labor induction with
      headache and convulsions as presentations--a case report.
AB  - The occurrence of complications of intracranial arteriovenous malformation (AVM)
      during labor induction is relatively uncommon. Intracranial AVM can cause
      convulsions, headache, focal neurological deficits and intracranial hemorrhage if
      ruptures. We present a 33-year-old parturient with history of paroxysmal
      supraventricular tachycardia, who was admitted for labor induction. She
      experienced a bout of convulsion following a 30-min oxytocin infusion, by which
      time it was three and half hours since she was given the test dose of epidural
      analgesic. She also denied having history of convulsions or preeclampsia.
      Magnetic resonance imaging (MRI) of brain demonstrated a cerebral AVM in the left
      frontal base without signs of intracranial hemorrhage or brain edema. The
      obstetrician opted for Cesarean section in order to avoid stress during vaginal
      delivery. The surgery was successfully performed under general anesthesia without
      hemodynamic fluctuations or neurological complications. We discuss the possible
      mechanisms of the convulsions attack in this patient and the ensuring anesthetic
      management for the Cesarean section she sustained.

PMID- 16450602
TI  - Latrogenic aortic dissection during mitral valve replacement surgery--a case
      report.
AB  - Intraoperative aortic dissection is one of the complications of aortic
      cannulation, which is potentially lethal with an incidence of about 0.16%. Early
      diagnosis and treatment can lower the mortality rate effectively. We report a 68
      y/o female patient sustaining an acute type A aortic dissection in consequence of
      aortic cannulation for mitral valve replacement surgery. Induction of general
      anesthesia and endotracheal intubation were performed smoothly. Transesophageal
      echocardiography (TEE) has proven itself as an important tool to offer definite
      diagnosis of aortic dissection. Iatrogenic intraoperative aortic dissection is
      rare but is potentially a fatal complication. Early diagnosis and prompt
      treatment are important for survival.

PMID- 16450603
TI  - Renal vascular injury during percutaneous nephrolithotomy and migration of a
      double-J catheter fragment into pulmonary artery in the following nephrectomy--a
      case report.
AB  - A 60-year-old male underwent percutaneous nephrolithotomy (PCNL) for left renal
      stone at a community hospital. The surgery was, in general, unremarkable and a
      double-J ureteral catheter was placed before completion of surgery. Dyspnea,
      irritability, hypotension and flank pain developed in the recovery room. In
      addition, pleural effusion and elevation of the left hemidiaphragm were revealed
      on chest roentgenogram, and mild hypoxemia and respiratory acidosis were also
      detected by gas analysis. He was transferred to our hospital for further
      management. After arrival at our hospital, we decided to reintubate the patient
      and transfer him to the intensive care unit (ICU). There, the vital signs
      deteriorated, so an emergent laparotomy was performed and left nephrectomy was
      done because of severe and unmanageable renal hemorrhage. A catheter fragment was
      found to be missing after left kidney was dissected. During the search for the
      missing fragment, pulseless electrical activity (PEA) happened. The patient
      recovered shortly after the use of vasopressors. Postoperatively, a chest X-ray
      (CXR) taken to search for the missing section of the cather revealed that there
      was a catheter-like foreign body in the heart, which was also demonstrated by
      computed tomography (CT) scan. The catheter fragment was quickly removed soon via
      percutaneous angiography. The patient was discharged 2 weeks later. We present
      this case with two iatrogenic complications, each in two consecutive renal
      procedures, to emphasize the importance of vigilance in anesthesia.

PMID- 16450604
TI  - 2005 National Caring Award winner. Sister Antonia Brenner. Bringing an angel's
      touch to life in prison.

PMID- 16450605
TI  - 2005 National Caring Award winner. Alice Coles. Delivering people promised land.

PMID- 16450606
TI  - 2005 National Caring Award winner. Father Theodore Hesburgh. Serving God, country
      and Notre Dame.

PMID- 16450607
TI  - 2005 National Caring Award winner. Alfredo J. Molina. Taking philanthropy to a
      higher level.

PMID- 16450608
TI  - 2005 National Caring Award winner. Genny Nelson. Listening to and serving the
      homeless.

PMID- 16450609
TI  - 2005 National Caring Award winner. Dr. Gloria Wilderbrathwaite. Bringing love and
      health care to those most in need.

PMID- 16450610
TI  - 2005 National Caring Award winner. Mother Mary Ann Wright. A modern miracle of
      loaves and fishes.

PMID- 16450611
TI  - 2005 National Caring Awards Youth winner. Kyle Amber. Founder--"Kids that Care".

PMID- 16450612
TI  - 2005 National Caring Awards Youth winner. May Lan Dong. Founder--Operation West
      Africa.

PMID- 16450613
TI  - 2005 National Caring Awards Youth winner. Jacob Komar. Founder--"Computer for
      Communities".

PMID- 16450614
TI  - 2005 National Caring Awards Youth winner. Aishlinn O'Connor. Founder--"Kids
      Helping Kids".

PMID- 16450615
TI  - 2005 National Caring Awards Youth winner. Greg Sweeney. Founder--Cub Scout Pack
      506.

PMID- 16450616
TI  - A tribute to the Honorable Robert J. Dole.

PMID- 16450618
TI  - Linking operations and health services research.

PMID- 16450617
TI  - Caring = do unto others.

PMID- 16450619
TI  - Shooting arrows in the dark: the policies and practices of waitlist management in
      Canada.
AB  - Wait times for medical procedures in Canada are universally thought to be too
      long, particularly for elective procedures. In this paper we point out the
      conceptual and practical difficulties surrounding wait list management in Canada.
      We suggest that while waits need to exist as a distributive allocation policy,
      the data to make informed decisions about wait times and their impact on patient
      care is absent. We also show that current waitlist initiatives lack an underlying
      conceptual model of why waits occur. The paper concludes with a discussion of why
      operational research (OR) models are not in greater use for wait list management
      and suggest a program of research to improve knowledge uptake for OR models.

PMID- 16450620
TI  - Overcoming the barriers to implementation of operations research simulation
      models in healthcare.
AB  - Since the 1960s, Operations Research models have been applied to a range of
      healthcare problems. Despite the proliferation of papers in the academic
      literature, and individual anecdotal success stories, there are still major
      issues around getting OR models widely accepted and used as part of mainstream
      decision-making by clinicians, health managers and policy-makers. In this paper,
      focussing on simulation models, we discuss some of the possible reasons for this,
      briefly describe one successful implementation and suggest some potential ways
      forward.

PMID- 16450621
TI  - Bottleneck analysis of emergency cardiac in-patient flow in a university setting:
      an application of queueing theory.

PMID- 16450622
TI  - A Canadian network for modeling and simulation in healthcare.

PMID- 16450624
TI  - Beginning patient flow modeling in Vancouver Coastal Health.
AB  - This paper reports on the development of patient flow modeling in Vancouver
      Coastal Health (VCH). The first section provides the context for the initiative.
      The organizational priority is then presented, with the project's purpose and
      goals. The initial models are briefly identified. The paper closes with examples
      of possible future directions for modeling in VCH.

PMID- 16450623
TI  - Don't panic--prepare: towards crisis-aware models of emergency department
      operations.
AB  - The existing models of Emergency Department (ED) operations that are based on the
      "flow-shop" management logic do not provide adequate decision support in dealing
      with the ED overcrowding crises. A conceptually different crisis-aware approach
      to ED modelling and operational decision support is introduced in this paper. It
      is based on Perrow's theory of "normal accidents" and calls for recognizing the
      inevitable nature of ED overcrowding crises within current health system setup.
      Managing the crisis before it happens--a standard approach in crisis management
      area--should become an integral part of ED operations management. The potential
      implications of adopting such a crisis-aware perspective for health services
      research and ED management are outlined.

PMID- 16450625
TI  - Mathematical methods to assist with hospital operation and planning.
AB  - Within health Operational Research, the use of 'computer package' methods such as
      simulation and system dynamics is becoming so prevalent that it feels somewhat
      old hat to use analytical methods to develop explicit mathematical formulae or
      even to explore the mathematical structure of problems. This paper will discuss
      the use of such 'back of the envelope' analysis illustrating its usefulness. It
      will be shown that not only does this approach yield considerable insight, but
      also that it can give rise to powerful and practical solution methods. Examples
      of this will be discussed in relation to issues such as bed needs estimation,
      admissions and facilities planning. The author is Director of the Clinical
      Operational Research Unit (CORU) which was established in 1983, receiving core
      funding from the UK Department of Health. The concept of a full time university
      based research unit dedicated to applying expertise in Operational Research (OR)
      to problems in health care provides a relatively rare research resource. Yet, the
      scope for such research, applied to an increasing range of health care activity,
      is enormous. Issues such as treatment evaluation, performance measures, clinical
      governance, evidence based medicine and health service delivery are all amenable
      to OR. Further, OR often provides an immensely cost effective alternative to
      traditional methods of clinical research based on randomised controlled trials or
      large scale epidemiological studies. The nature of OR, and one of its main
      strengths, is that it encompasses a wide range of analytical and scientific
      methods. Mathematical modeling, statistics, computer-based methods, trial design
      and analysis all contribute to health OR and, under both of its Directors since
      1983, a conscious effort has been made within CORU to foster a diversity of
      research methodologies. Particular emphasis is put on developing new mathematical
      methods and computer software. This is somewhat at odds with what seems to be a
      growing trend in health OR towards researchers specialising in just one or two
      areas of methodology; thus Tom does queueing theory, Dick does simulation and
      Harry does System Dynamics. Of course there are exceptions, but for whatever
      reason, the trend towards specialisation seems real. In this paper, benefits of a
      more diverse approach to health OR is advocated, particularly the use of 'back of
      envelope' mathematical methods as an alternative to the use of proprietary
      software packages. Three case studies are described to illustrate this approach.

PMID- 16450626
TI  - Modeling change in a health system: implications on patient flows and resource
      allocations.
AB  - This work is motivated by the recent changes in the health system in Turkey,
      which is a consolidation of health insurance funds, and its implications on the
      resource allocations and the flow of patients in the system. Our aim is to
      provide a model to find the best reallocation of resources between the hospitals
      and the best patient-hospital match to minimize the costs.

PMID- 16450627
TI  - On comprehensive and realistic modeling: some ruminations on the what, the how
      and the why.

PMID- 16450628
TI  - Combining data mining tools with health care models for improved understanding of
      health processes and resource utilisation.
AB  - Variability and uncertainty are inherent characteristics of most health care
      processes. Patient pathways and dwelling times even within the same process
      typically vary from patient to patient, such as the flow of patients through a
      particular health care provider or patient progression through the natural
      history of a given disease. The challenge for the OR modeller is to adequately
      handle and capture the stochastic features within developed models. This paper
      will discuss the benefits of combining patient classification tools (data mining
      techniques) with developed OR models, such as simulation tools, to more
      accurately capture patient outcomes, risks and resource needs. Illustrative
      applications will demonstrate the approach.

PMID- 16450629
TI  - Hillmaker: an open source occupancy analysis tool.
AB  - Managerial decision making problems in the healthcare industry often involve
      considerations of customer occupancy by time of day and day of week. We describe
      an occupancy analysis tool called Hillmaker which has been used in numerous
      healthcare operations studies. It is being released as a free and open source
      software project.

PMID- 16450630
TI  - The challenge of modeling patient safety risk management in a complex health care
      environment.

PMID- 16450631
TI  - Categorizing outcomes of health care delivery.
AB  - After a patient presents with symptoms of illness and undergoes treatment, there
      are three features of care that require assessment: the impact of delivering care
      on the patient, the benefits and harms of treatment, and the functioning of the
      health care system. This formulation leads to three types of outcomes of care
      delivery that require assessment: 1) patient outcomes, which reflect the impact
      on patients of undergoing care; 2) treatment outcomes, which reflect the intended
      and unintended medical consequences of undergoing therapy; and 3) system
      outcomes, which reflect the impact on the system of delivering health care to a
      group of patients. In this paper, examples of these three types of outcomes are
      presented, with particular reference to coronary artery bypass graft surgery. It
      is argued that the current focus of computer simulation models on system outcomes
      should be expanded to include patient and treatment outcomes.

PMID- 16450632
TI  - Toward patient centric and distributed healthcare delivery networks.

PMID- 16450633
TI  - An operating room block allocation model to improve hospital patient flow.

PMID- 16450634
TI  - Seven rules for modeling health care systems.

PMID- 16450635
TI  - Policy analysis using patient flow simulations: conceptual framework and study
      design.
AB  - How do we know that innovations in healthcare delivery would work? In this paper,
      we discuss the idea of applying the methodology of group-randomized intervention
      studies to evaluation of surgical care policies using data from simulation
      experiments. We argue that a new interdisciplinary framework, which links health
      services research, operations research, and computer sciences, is required.
      Specifically, the methodological rigor of evaluative studies should be applied to
      the analysis of simulation experiments. In turn, the evaluation of policy
      initiatives should include the simulation of health-system operations. We
      introduce the framework and study design to evaluate methods for improving the
      peri-operative process with the use of patient flow simulations.

PMID- 16450636
TI  - An outpatient segmentation model: estimation of stakeholder costs.
AB  - This research describes a constraint-based heuristic model of capacity
      segmentation for outpatient facilities used to estimate the effect of
      segmentation constraints on stakeholders. Growth of free-standing ambulatory
      surgery centres has been dramatic in recent years with institutions being urged
      by governments and insurers to segment inpatients (IP) and outpatients (OP) to
      reduce costs and improve services. Critics of segmentation argue it is a false
      economy to separate inpatients and outpatients since pooling of patients in large
      IP facilities offers economies of scale and opportunities for parallel
      processing, not to mention elimination of infrastructure. We implemented a
      constraint-based heuristic model of capacity segmentation for OP facilities and
      used it to estimate the effect of segmentation on stakeholders.

PMID- 16450637
TI  - Comparing two methods of scheduling outpatient clinic appointments using
      simulation experiments.

PMID- 16450638
TI  - On the significance of reducing the need for stroke patients to visit the
      emergency department.
AB  - We studied the care-provider paths followed by 3,946 patients in Quebec in 2001.
      We showed that the patients flow during the three months preceding discharge from
      hospital can be represented by a Markov model with memory. This model enables
      study of four major scenarios to improve health outcomes, workloads and cost
      efficiency in the overall community-based care delivery system. Based on the
      field data, we establish that increasing the availability of specialists, family
      physicians and general practitioners to mitigate the need for ER visits would be
      an effective strategy for improvement. A comprehensive policy to support stroke
      patients needs to incorporate both hospital-based and community-based care
      delivery processes. The seamless flow of patients through the healthcare
      providers in such an integrated system is crucial for achieving successful
      outcomes. Emergency rooms (ER) have a crucial role in this context, since in many
      cases ER acts as the hospital's "gate keeper", determining if a patient needs to
      be (re)admitted. In this paper, we establish (based on field data) that
      mitigating the ER visits of stroke patients improves health outcomes,
      distribution of workload across the healthcare system as well as associated
      costs. To this end, we make use of a Markov modeling framework, where the
      aggregate patient flow information is represented in a compact form through the
      use of a transition-probability matrix. This allows us to investigate the system
      wide impact of several plausible scenarios with regards to the delivery of
      community-based care to stroke patients who are recently discharged from
      hospital.

PMID- 16450639
TI  - Support for buprenorphine and methadone prescription to heroin-dependent patients
      among New York City physicians.
AB  - Methadone and buprenorphine are treatments for heroin-dependent patients.
      Methadone is available through highly-regulated treatment centers while
      buprenorphine was approved in 2002 for prescription by certified physicians. Just
      prior to the approval of buprenorphine, we conducted a random postal survey of
      770 physicians in New York City to determine willingness to prescribe methadone
      or buprenorphine for heroin-dependent patients to be picked up at a pharmacy.
      Among 247 respondents, 36.3% would consider prescribing methadone and 17.9% were
      unsure, while 25.8% would consider prescribing buprenorphine and 31.8% were
      unsure. Willingness to prescribe methadone or buprenorphine was associated with
      more recent year of licensure (p = 0.044; p = 0.033), working in a hospital or
      clinic as opposed to an office setting (p = 0.009; p = 0.024), and being the
      director of a clinic or program (p = 0.031; p = 0.008). This preliminary study
      suggests that a substantial proportion of New York City physicians would
      prescribe methadone or buprenorphine to heroin-dependent patients.

PMID- 16450640
TI  - Predictors of prison-based treatment outcomes: a comparison of men and women
      participants.
AB  - The purpose of this study was to examine differences between men and women
      entering prison-based therapeutic community (TC) treatment and to explore the
      relationship of those differences to posttreatment outcomes (i.e., aftercare
      participation and reincarceration rates). Extensive treatment-intake interview
      data for 4,386 women and 4,164 men from 16 prison-based TCs in California were
      compared using chi-square analyses and t-tests. Logistic regression analyses were
      then conducted separately for men and women to identify gender-specific factors
      associated with post-treatment outcomes. Prison intake data and treatment
      participation data come from a 5-year process and outcome evaluation of the
      California Department of Corrections' (CDC) Prison Treatment Expansion
      Initiative. The return-to-custody data came from the CDC's Offender Based
      Information System. Bivariate results showed that women were at a substantial
      disadvantage compared with their male counterparts with regard to histories of
      employment, substance abuse, psychological functioning, and sexual and physical
      abuse prior to incarceration. In contrast, men had more serious criminal justice
      involvement than women prior to incarceration. After controlling for these and
      other factors related to outcomes, regression findings showed that there were
      both similarities and differences with regard to gender-specific predictors of
      posttreatment outcomes. Time in treatment and motivation for treatment were
      similar predictors of aftercare participation for men and women. Psychological
      impairment was the strongest predictor of recidivism for both men and women.
      Substantial differences in background characteristics and the limited number of
      predictors related to posttreatment outcomes for women suggests the plausibility
      of gender-specific paths in the recovery process.

PMID- 16450641
TI  - Adolescent inhalant use among male patients in treatment for substance and
      behavior problems: two-year outcome.
AB  - Adolescent inhalant users are significantly more likely than other patients to
      have conduct disorder, to report abuse and neglect, and to have previously
      attempted suicide. Yet little has been published regarding treatment outcome for
      inhalant users. METHODS: Eighty male adolescents admitted to a residential
      treatment program underwent baseline assessment during treatment, and follow-up
      assessment at two-years post admission. Subjects reporting any lifetime inhalant
      use at baseline (n = 34) were compared to the other patients (n = 46) on 4
      outcome variables. RESULTS: Adolescents reporting any lifetime inhalant use at
      baseline assessment reported twice as many past-year conduct disorder symptoms at
      two-year follow up (p = 0.03). The relationship between inhalant use and conduct
      disorder symptoms remained significant (p = 0.03) in analyses that controlled for
      age, time in jail or restricted environments in the 6-months preceding follow-up,
      as well as baseline-reported lifetime number of conduct disorder symptoms.
      Inhalant users were not significantly worse on these other outcome measures:
      crime in the last month (p = 0.60), days of nontobacco substance use in the last
      6 months (p = 0.65), or, commission of selected crimes in the last 6 months (p =
      0.06). CONCLUSIONS: Inhalant use among adolescent males in treatment for
      substance and behavior problems may predict more severe conduct disorder symptoms
      after treatment.

PMID- 16450642
TI  - Risk for marijuana-related problems among college students: an application of
      zero-inflated negative binomial regression.
AB  - METHOD: This study examined the association between marijuana-related problems
      and social norms, impulsivity, and perceived use utility among 292 college
      students. Zero-inflated negative binomial regression was used to simultaneously
      predict expected nonusers as well as predict counts of reported marijuana-related
      problems among expected users. Gender, social norms, impulsivity, and perceived
      use utility were used to predict expected nonusers as well as number of marijuana
      related problems among expected users. RESULTS: Only social norms were associated
      with the prediction of zero-values. In contrast, only perceived use utility was
      associated with the prediction of number of marijuana-related problems.
      CONCLUSIONS: Results generally are consistent with theories of the differential
      association of social-environmental and biopsychological variables with use and
      problems, respectively. Zero-inflated regression models are a useful strategy to
      examine risk behaviors with low base rates.

PMID- 16450643
TI  - Emergency department utilization by crack-cocaine smokers in Dayton, Ohio.
AB  - The objective of this study was to determine the frequency, principal diagnoses,
      and correlates of emergency department (ED) visits made by persons with a history
      of crack-cocaine use (n = 333) over a 3-year period. Data were collected from
      participant self-reports and hospital records. During the study a total of 643 ED
      visits were made by 211 people, ranging from 53.5 to 76.7/100 persons/year.
      Injury and poisoning accounted for the largest single category of ED visits
      (29.5%). Men had lower odds of visiting the ED (OR=0.79, 95%CI=0.62-0.99), as did
      participants with higher levels of education (OR=0.83, 95%CI=0.73-0.94). Number
      of times in drug abuse treatment (OR=1.04, 95%CI=1.01-1.09), having a chronic
      disease (OR=1.46, 95%CI=1.06-1.99), and higher Addiction Severity Index composite
      medical scores (OR=1.62, 95%CI=1.15-2.29) increased the odds of an ED visit.
      Factors in addition to drug use are likely to affect ED utilization rates among
      crack-cocaine smokers.

PMID- 16450644
TI  - Assessing the service linkages of substance abuse agencies with mental health and
      primary care organizations.
AB  - Fragmentation of substance abuse treatment represents a major barrier to
      effective treatment for individuals with cooccurring substance abuse and mental
      and physical health disorders. Linkages of substance abuse treatment
      organizations with primary care and mental health agencies are widely considered
      to be a feasible way to integrate services. In this study, we analyzed
      information collected from a national sample of 62 outpatient substance abuse
      treatment units (OSATs) to understand the extent of services linkages in these
      organizations and to identify facilitators and barriers to service linkages.
      Results showed that OSATs had limited service linkages with primary care and
      mental health providers. The cited barriers to linkages included clients'
      financial problems, managed care restrictions, and limited organizational
      capacity. Onsite service provision was implemented in some OSATs. The pattern of
      service linkages in OSATs appeared to reflect the health needs of substance abuse
      clients.

PMID- 16450646
TI  - Screening for substance use patterns among patients referred for a variety of
      sleep complaints.
AB  - Virtually all psychiatric and substance use disorders are associated with sleep
      disruption. Studies indicate that psychiatric disorders are related closely to
      chronic insomnia and that psychoactive substances have acute and chronic effects
      on sleep architecture. Several aspects of sleep are compromised in individuals
      taking these substances, ranging from difficulty initiating sleep to difficulty
      maintaining sleep and hypersomnia. Sleep disturbances are apparent in person
      taking psychoactive drugs or alcohol and have been found to persist long after
      withdrawing from these drugs. For some, sleep disturbance can be so severe as to
      reverse treatment success and precipitate relapse to addiction or dependence.
      There is increasing evidence that primary insomnia without a concurrent
      psychiatric disorder is a risk factor for later developing substance use
      disorders. Patients were asked to complete two brief screening tools, the
      Michigan Alcohol Screening Test and Drug Abuse Screening Test, to examine
      substance use patterns among patients referred for a variety of sleep complaints
      in a sleep disorders clinic. We found that patients who demonstrated a variety of
      sleep complaints were more likely to have alcohol and drug problems than those in
      the general populations.

PMID- 16450645
TI  - Substance abuse among rural and very rural drug users at treatment entry.
AB  - Historically, researchers and policymakers concerned with the problems of
      substance abuse have focused their attention almost exclusively on urban America.
      However, this focus now includes the special needs of rural areas. In the past,
      rural areas were more sheltered from the problems of mainstream America, but now,
      mass communication has decreased the isolation of rural areas. The purpose of
      this study is to examine rural and very rural drug users; including: (a)
      demographic and other selected background characteristics of rural and very rural
      drug users admitted to substance abuse treatment, (b) lifetime drug use patterns,
      (c) current drug use, (d) age of first drug use, (e) recognition of drug abuse as
      a problem, and (f) correlates of drug use behavior to identify potential
      predisposing factors. It was hypothesized that drug users from very rural areas
      would be more sheltered and the severity of their involvement with drug use would
      be less than that of drug users from rural areas. Between November 15, 1999 and
      January 31, 2001, face-to-face interviews were conducted in three geographic
      regions of Kentucky (N=604); eastern Kentucky (n=206), south central Kentucky (n=
      165)--both frequently are considered rural (n=371)--and Western Kentucky, which
      is considered more urban (N=233). Over half of the participants were admitted to
      outpatient treatment (57%). The majority of participants were male (75%), White
      (94%), had no religious preference (51%), had been referred to by the criminal
      justice system (64%), and had a history of prior substance abuse treatment (55%).
      Findings indicate that being from very rural areas may be somewhat protective
      with lower current drug use and older age at drug use initiation. While alcohol
      remains the most used substance in terms of lifetime and current use, cocaine use
      was three times higher in rural areas than in very rural areas. Implications are
      discussed and recommendations are presented for substance abuse treatment
      providers and policymakers.

PMID- 16450647
TI  - Predictive validity of the RIASI: alcohol and drug use and problems six months
      following remedial program participation.
AB  - The ability of screening instruments for convicted drinking drivers to predict
      subsequent alcohol and drug-related problems rarely has been studied. The
      predictive validity of the Research Institute on Addictions Self-Inventory
      (RIASI) was investigated in a sample of 6,003 convicted drinking drivers who were
      participating in Back on Track (BOT), Ontario's remedial measures program for
      convicted drinking drivers. All BOT participants complete an assessment (which
      includes the RIASI), followed by a brief education or treatment program, and
      concluded 6 months later by a follow-up interview. The follow-up interview
      collects information on self-reported alcohol and other drug use and problems,
      and contacts with other health care providers in the 90 days prior to the follow
      up contact. The ability of scores on the RIASI to predict these measures was
      assessed. The results revealed that, for almost all comparisons, individuals who
      used alcohol and other drugs, reported more substance-related problems at follow
      up, and reported more contacts with other health and addictions providers had
      significantly higher scores on the RIASI total score and the RIASI recidivism
      scale at the initial assessment. The data indicate that this instrument appears
      to be able to identify individuals who will experience alcohol and drug related
      problems in the future.

PMID- 16450648
TI  - Make war history.

PMID- 16450649
TI  - Lessons from the unsuccessful 2005 Nuclear Non-Proliferation Treaty Review
      Conference.
AB  - The Nuclear Non-Proliferation Treaty is probably the most important treaty for
      the control of nuclear weapons. A Review Conference was held in May 2005 but the
      member states failed to agree on any decisions or recommendations. Possible
      causes for this failure reside in the unsupportive geopolitical climate
      surrounding the conference, design limitations of the Treaty, and the
      obstructionist actions of particular states. However, valuable contributions were
      made at the conference by some states and by civil society representatives.
      Fortunately there are still many ways for states and civil society to make future
      conferences more successful in eliminating the threat to human security from
      nuclear weapons.

PMID- 16450650
TI  - With war in mind: a dialogical analysis of the mindset underlying Blair's case
      for war with Iraq in 2003.
AB  - Dialogical Analysis, a tool from Cognitive Analytic Therapy, is used to discover
      how the mindset of war silences dialogue. The savage costs of war were hidden
      whilst the United Kingdom government expected to attract the admiration of a
      grateful world. This article looks at an example of this mindset expressed
      through Tony Blair MP's speech to the House of Commons on 18 March 2003. The
      speech aimed at convincing parliament that war was inevitable, necessary and the
      only obvious choice. It offered an extremely narrow presentation of options
      available to the government, in which 'staying firm' was coupled with the case
      for war whilst alternative, peaceful methods of conflict resolution were
      identified as 'weak and feeble' and viewed as encouraging terrorists.

PMID- 16450651
TI  - The role of health professionals in preventing and mediating conflict.
AB  - Since the early 1980s academics, governmental and non-governmental organisations
      have undertaken field projects inspired by the Peace through Health and similar
      concepts formulated by the World Health Organisation and the Department of Peace
      Studies at McMaster University, Canada. These have been criticised for lack of
      proper evaluation, the appropriateness of the skills of health workers involved,
      and the overall usefulness of the approach. This article, based on a literature
      review, compares existing evidence with the theoretical framework. There is still
      a lack of systematic evaluation, but no direct disproof of Peace through Health
      theory. It is concluded that the Peace through Health approach can have a
      positive impact on healing and reconciliation on a community scale, but there is
      no evidence of a peace impact on a larger scale.

PMID- 16450652
TI  - The impact of small arms on health in Nigeria.
AB  - Nigeria, the most populous Black country in the world, though it has contributed
      to the welfare of other African countries, is plagued by internal conflicts with
      small arms. Over a million illegal small arms circulate in Nigeria in the hands
      of militant groups. Over 10,000 may have died in conflicts between these groups
      and the government. Quality health care is unavailable in much of the country,
      and small arms injuries often overstretch emergency health care. A national
      committee has been set up to implement the ECOWAS moratorium on small arms and
      light weapons, but much remains to be done.

PMID- 16450653
TI  - Patient safety: a renewed focus.

PMID- 16450654
TI  - Asthma: an important comorbidity of allergic rhinitis.

PMID- 16450655
TI  - An algorithm-for local non-surgical management of complicated wounds in head and
      neck cancer patients.
AB  - This review paper introduces an algorithm for non-surgical local wound care in
      head and neck cancer patients who have delayed and complicated wound healing.
      Wound complications are common in patients undergoing head and neck cancer
      treatment, regardless of whether their primary treatment modality is surgery or
      chemoradiation. The risk for complications is compounded by the vital structures
      in the regional anatomy of these tumors and by the toxicities and long-term
      consequences of the cancer treatments employed. There is limited empirical and
      clinical evidence to specifically guide and improve local wound healing outcomes
      in head and neck cancer patients. The algorithm, based on an analysis of the
      medical literature, begins with the assessment of five simple wound environment
      characteristics: exudate volume; slough and eschar; large vessel exposure;
      proliferation; and systemic nutrition and perfusion. Assessing these wound
      characteristics is the basis for planning local care. The wound characteristics
      are discussed in relation to the pertinent literature, product categories, and
      other known interventions presented herein.

PMID- 16450656
TI  - Creating our country's laws.

PMID- 16450657
TI  - Ten tips for streamlined surgery scheduling.
AB  - Despite its operational importance, there are few academic references available
      related to efficient and effective surgery scheduling. This article outlines ten
      practical tips for streamlining the process of scheduling surgeries.

PMID- 16450658
TI  - Hispanic access to hospice services in a predominantly Hispanic community.
AB  - Although the largest minority population in the United States, Hispanics are
      under-represented in hospice at the national level. The study purpose was to
      document Hispanic access to hospice services in an environment where Hispanics
      are a majority population. The framework for the study was Aday and Anderson's
      model for access to medical care. In this framework, access is not defined as
      availability of services and resources, but whether services are actually used by
      the people who need them. We completed retrospective chart reviews of 500
      Medicare beneficiaries who died in four hospices. Study variables were decedent
      characteristics and access to hospice and hospice disciplines. Results showed
      that Hispanics and whites differed on characteristics known to influence access
      to health services, e.g., preferred language and type of caregiver Although the
      proportion of Hispanic elders dying in hospice was less than the proportion
      living in the community, the proportions of Hispanic elders who died in the
      community or died in their homes were not differentfrom the proportion that died
      in hospice. When access to hospice disciplines was compared between Hispanic and
      white decendents, the results showed one difference-more whites than Hispanics
      had access to volunteer services. Overall, the study showed that Hispanics were
      not underrepresented in hospice, and they had equal access to hospice
      disciplines. These findings differ from national data and may be associated with
      Hispanics being the majority population in the community. To learn how population
      dominance influences minority access to services, Hispanic access to hospice
      could be studied in locales with varying proportions of Hispanics in the
      population.

PMID- 16450659
TI  - Deathbed phenomena and their effect on a palliative care team: a pilot study.
AB  - Anecdotal evidence suggests that death may be heralded by deathbed phenomena
      (DBP) such as visions that comfort the dying and prepare them spiritually for
      death. Medical practitioners have been slow to recognize DBP, and there has been
      little research into the spiritual effect that DBP have on caregivers or on how
      these phenomena influence their work. A pilot study looking into the occurrence
      of DBP was conducted by the palliative care team at Camden Primary Care Trust.
      Interviews revealed that patients regularly report these phenomena as an
      important part of their dying process, and that DBP are far broader than the
      traditional image of an apparition at the end of the bed. Results of the
      interviews raise concerns about the lack of education or training to help
      palliative care teams recognize the wider implications of DBP and deal with
      difficult questions or situations associated with them. Many DBP may go
      unreported because of this. Results of this pilot study also suggest that DBP are
      not drug-induced, and that patients would rather talk to nurses than doctors
      about their experiences.

PMID- 16450661
TI  - Use of methylphenidate in patients with cancer.
AB  - Cancer and its treatment are often associated with symptoms such as depression,
      somnolence, cognitive abnormalities, and fatigue. Methylphenidate, a stimulant
      medication, is commonly used to treat these symptoms. Several small pilot and a
      few adequately powered studies have assessed the safety and efficacy of
      methylphenidate in patients with cancer Overall, the studies so far suggest that
      methylphenidate is well-tolerated in patients with cancer Further, the studies
      have provided initial evidence of efficacy of this agent in patients with cancer
      The present article reviews the evidence base behind the use of methylphenidate
      in these patients.

PMID- 16450660
TI  - Screening the soul: communication regarding spiritual concerns among primary care
      physicians and seriously ill patients approaching the end of life.
AB  - The purpose of this study was to explore the spiritual concerns of seriously ill
      patients and the spiritual-care practices of primary care physicians (PCPs).
      Questionnaires were administered to outpatients (n=65, 90 percent response rate)
      with end-stage illness and to PCPs (n=67, 87 percent response rate) in a diverse
      general medicine practice. Most patients (62 percent) and PCPs (68 percent)
      considered it important that physicians attend to patients 'spiritual concerns.
      However, few patients reported receiving such care, and most (62 percent) did not
      think it was the PCP's job to talk about spiritual concerns. Although both
      seriously ill outpatients and PCPs assert the importance of spiritual concerns,
      PCPs often do not provide spiritual care. Appropriate provision of spiritual care
      within a diverse population of seriously ill outpatients is complex,
      necessitating appropriate and attentive screening.

PMID- 16450662
TI  - A prospective randomized controlled clinical trial of zoledronic acid for bone
      metastases.
AB  - In this study, we assessed the safety, tolerability, and effectiveness of two
      therapeutic regimens relating to the frequency of zoledronic acid (ZOL) infusion.
      Sixty adult patients with bone metastases were randomly assigned to two study
      groups. The first group (group A) received 4 mg ZOL every two weeks, and the
      second group (group B) received 4 mg ZOL every four weeks. Assessment measures
      included C-telopeptide (CTX) rate, the Greek Brief Pain Inventory (GBPI), the
      linear analogue scale assessment (LASA) of quality of life, and biochemical
      markers. Assessments were made at weeks 12, 24, 36, and 48. Clinical endpoints
      included effective decrease in bone resorption markers, pain relief and
      improvement of mobility status. The follow-up period was 48 weeks. No
      statistically significant differences between groups A and B were found in
      overall profile of biochemical markers, Eastern Cooperative Oncology Group (ECOG)
      performance status, and GBPI score at the end of the follow-up period. Assessment
      of bone metastases revealed a slight difference between the two groups, however
      this difference was not statistically significant. These findings indicate that
      administering zoledronic acid at four rather that two weeks has no significant
      impact on overall outcome.

PMID- 16450663
TI  - Urban and rural differences in end-of-life pain and treatment status on admission
      to a nursing facility.
AB  - Individuals receiving end-of-life (EOL) care may have needs that are unrecognized
      or treated inappropriately. Yet, very little is known about differences in pain
      and special-care needs of EOL patients admitted to rural nursing facilities
      compared with urban nursing facilities, and whether the differing payer mix in
      urban and rural facilities affects the treatment ordered on admission. We examine
      a nationally representative sample of 6084 EOL patients upon admission to nursing
      homes to examine differences in diseases, pain assessments, and treatment orders.
      We found that rural EOL residents have higher rates of congestive heart failure,
      cancer, renal failure, and emphysema than urban EOL residents and are
      significantly more likely to report frequent pain, however, they are less likely
      to receive treatments such as IV medications, dialysis, and wound care.

PMID- 16450664
TI  - Case study: advisability of partial-code orders.

PMID- 16450666
TI  - Were we the problem?

PMID- 16450665
TI  - Doctors visiting the dying patient: medicine for family distress.

PMID- 16450667
TI  - The ongoing battle over economic credentialing.

PMID- 16450669
TI  - Critical review.

PMID- 16450668
TI  - Preventive services vital for children, state, providers.

PMID- 16450670
TI  - Parsonage Turner syndrome.

PMID- 16450671
TI  - Meet our members: Clay W. Ferguson, MD.

PMID- 16450673
TI  - Anesthetic management of Down syndrome: a review.

PMID- 16450672
TI  - Spine bone densitometry in asthmatic children treated with high dose
      corticosteroids: correcting for racial discrepancies.
AB  - PURPOSE: Our hypothesis is that the use of standards based on Caucasian children
      will under-estimate the incidence of abnormal bone density in African American
      children. MATERIALS AND METHODS: Eighty-two African American and 80 Caucasian
      asthmatic children classified as high-dose inhaled corticosteroid users comprised
      the study population. Bone mineral density measurements were compared to
      reference standards, based on Caucasians, to calculate Z-values. Regression
      analysis was used to compare Z-values derived from the race-specific and
      Caucasian standards for 32 African American children. The derived regression
      analysis equation was then applied to the entire African American population to
      determine the incidence of abnormal bone density. RESULTS: The asthmatic
      Caucasian mean spine bone density was significantly less than the normal
      standards (p < .001), but the African American mean spine bone density was not,
      despite the high-dose steroid use. Using the Caucasian standards, Caucasians were
      significantly more likely to have abnormal bone density detected (p < 0.015).
      Regression analysis of the 32 children with available race specific standards
      resulted in the following equation: Z African American= Z Caucasian-0.86. The
      number of African Americans with abnormal bone density detected using the
      regression equation was not significantly different than the Caucasian children
      (p > 0.12). CONCLUSIONS: Asthmatic African Americans treated with high-dose
      inhaled corticosteroids had denser bones than Caucasians. Caucasian standards can
      be adjusted using a regression equation.

PMID- 16450674
TI  - Insecticide-treated nets in the prevention of malaria.

PMID- 16450676
TI  - Determinants of immunisation coverage in Butere-Mumias district, Kenya.
AB  - BACKGROUND: Butere-Mumias district is one of the districts which performs poorly
      on immunisation coverage, as observed from the Kenya Expanded Programme of
      Immunisation reports. OBJECTIVE: To identify factors that contribute to the low
      level of immunisation coverage in the district among children under the age of
      five years. DESIGN: Cross-sectional descriptive study. SETTING: Butere-Mumias
      district. RESULTS: Out of the 293 mothers who were sampled, 238 (80%) had
      attained primary level of education while, 55 (20%) attained secondary level and
      above. Immunisation coverage was found to be 35% in this district. Long distances
      to health facilities, poor states of the roads, age, attitude and knowledge
      regarding immunisation among mothers were significant factors that determined
      immunisation coverage. CONCLUSION: Low levels of education, long distances to the
      nearest health facilities, lack of knowledge on immunisations and lack of staff
      were responsible for the low coverage. There is therefore, need to act on these
      factors which hamper the immunisation coverage in order to reduce child mortality
      rate which are attributable to non-immunisation.

PMID- 16450675
TI  - Maternal use of insecticide-treated nets in the prevention of malaria among
      children under five years in Nyamira district, Kenya.
AB  - BACKGROUND: Insecticide treated nets (ITNs) have been proved as one of the most
      effective ways of reducing malaria morbidity and mortality in children and
      pregnant women. Proper use and care of insecticide treated nets reduce malaria
      health risk to children. OBJECTIVE: To determine maternal use of insecticide
      treated nets in the prevention of malaria among children under five years in
      Nyamira district. DESIGN: Cross-sectional, descriptive study. SETTING: Eight
      health centres in Nyamira district. SUBJECTS: Four hundred mothers bringing their
      children aged five years and below to the child health clinics between August and
      October 2003. RESULTS: There was very low usage of mosquito nets (33.8%) with the
      proportion of under five using bed nets and insecticide treated nets being 33.3%
      and 23.8% respectively. The possibility of a mother having an insecticide treated
      net was significantly related with the level of education of the mother (p =
      0.003), occupation (p = 0.001) and knowledge (p = 0.000). Among the reasons given
      by mothers regarding non usage of insecticide treated nets included lack of
      money, they were expensive, ignorance and carelessness. CONCLUSION: There was low
      use of ITNs (23.8%) among children. There is need for health information,
      education and communication campaigns to sensitise the mothers on most risk
      groups from malaria so as to create awareness of who needed more protection
      through use of ITNs. There is need for ITNs intervention projects for malaria
      prevention in the area.

PMID- 16450677
TI  - Barriers to utilisation of eye care services in Kibera slums of Nairobi.
AB  - OBJECTIVES: To identify the main barriers to utilisation of eye care services
      among the slum population of Kibera in Nairobi, Kenya. DESIGN: Community based
      survey. SETTING: Kibera slums, Nairobi City, Kenya. SUBJECTS: Randomly selected
      1,438 Kibera slum dwellers aged over two years. RESULTS: Majority of subjects
      (83.3%) do not utilise the nearby well-established eye clinics. Twenty one
      percent of those with poor vision do not seek treatment at all. The main barriers
      to seeking eye care services were lack of money, ignorance and the problem not
      causing much discomfort to warrant medical attention. There was significant,
      association between the level of education and health seeking behaviour (P =
      0.008). CONCLUSION: Majority of Kibera slum dwellers have no access to eye care.
      RECOMMENDATION: There is need to establish a comprehensive primary eye care
      project to provide low cost but quality services affordable to Kibera slum
      dwellers.

PMID- 16450678
TI  - Pattern of bone loss in dry mandibles of individuals who died before 1957.
AB  - OBJECTIVE: To map out the pattern of periodontal disease in individuals who died
      before 1957 and were not exposed to formal dental services. DESIGN: Descriptive
      cross-sectional study. SETTING: National Museums of Kenya. SUBJECTS: The
      skeletons of people who died before independence are preserved at the National
      Museums of Kenya in Nairobi. Sixty four out of the 170 dry mandibles stored at
      the Museum were assessed for periodontal bone loss using a calibrated ruler.
      RESULTS: All the 64 mandibles assessed were of individuals who died before 1957.
      Two thousand two hundred and seventy four sites were examined. Most of the
      subjects were adults aged 30-45 years and the age range was 18-80 years. Majority
      of the mandibles examined were of the ethnic group from Central Kenya. Of the
      teeth examined, premolars and molars were the teeth most frequently preserved
      intact in the sockets. The total mean bone loss for all teeth was 2.51 (SD 1.15)
      with a range of 0.85-5.80. When the different sites were examined, values for
      bone loss were 2.59 for mesial surfaces; 2.55 buccal surfaces; 2.38 for distal
      surfaces. Three categories were identified as follows:- 70% of the individuals
      had minimal or no bone loss, 26.5% had 3-4 mm or moderate bone loss and 3.5% had
      >5 mm bone loss or advanced bone loss. Further analysis showed that when bone
      loss of >3 mm was examined, only 28.12% of the individuals were in this group,
      10.93% had >4 mm bone loss and 3.12% had 5 mm or more bone loss. The first molars
      were the teeth most commonly affected by bone loss of 3mm or more followed by
      second molars then the premolars. CONCLUSIONS: In this group of individuals
      mainly from Central Kenya, the bone loss pattern showed that only a small number
      had experienced periodontal destruction as recorded by bone loss levels. Three
      groups were identified; those who had no or minimal destruction, those who had
      experienced moderate destruction and those where obvious bone destruction was
      evident. Thus susceptibility to periodontal disease is evident in a small
      proportion of individuals even in populations not exposed to modern diet and
      formal dental services. Periodontal destruction seems to affect a fraction of the
      population even when older populations are examined, thus it would save on
      resources both human and physical if these susceptible individuals could be
      identified early and treatment provided.

PMID- 16450679
TI  - Echocardiographic patterns of juvenile rheumatic heart disease at the Kenyatta
      National Hospital, Nairobi.
AB  - OBJECTIVE: To describe the echocardiographic features of children with rheumatic
      heart disease seen at the Kenyatta National Hospital. DESIGN: A retrospective
      study. SETTING: The Kenyatta National Hospital Heart Unit. SUBJECTS: Patients
      aged 20 years and less with echocardiographic diagnosis of rheumatic heart
      disease. RESULTS: Two hundred and twenty four echocardiograms were analysed.
      Seventy six point four of cases were aged between 5 and 15 years, while on 3%
      were less than five years. The combinations mitral and aortic regurgitation was
      the most common lesion followed by isolated mitral regurgitation. Isolated aortic
      regurgitation was as rare as isolated mitral stenosis in the paediatric age group
      1.8% and 2.7% respectively. When seen in the younger age group, the leaflet
      morphology in mitral regurgitation was predominantly thickening and clubbing of
      the leaflets while in the older children the pathology was of marked fibrosis of
      the sub-valvular apparatus. Leaflet prolapse and commissural fusion was the major
      pathology in aortic regurgitation. Pulmonary hypertension was the most common
      complication commonly seen in mitral valve disease. Calcification was a rare
      encounter in this age bracket. CONCLUSIONS: Rheumatic heart disease in the
      paediatric age commonly presents as isolated mitral regurgitation or in
      combinations of mitral and aortic regurgitation. The complications of pulmonary
      hypertension was predominant in mitral valve disease. Valvular calcification is
      rare in juvenile rheumatic heart disease.

PMID- 16450680
TI  - Dietary patterns and nutritional status of pre-school children in Nairobi.
AB  - OBJECTIVE: To determine the dietary patterns and nutritional status of pre-school
      children in Nairobi, Kenya. DESIGN: A cross-sectional study. SETTING: Pre-schools
      in Nairobi, Kenya. SUBJECTS: Three hundred and four pre-school children (149
      males and 155 females) aged three to five years were assessed. RESULTS: About 96%
      of the children had been breastfed 46.7% of them for 12-24 months (46.7%), and
      the mean breastfeeding duration was 20.17 months. The most commonly consumed
      foods on a daily basis were fruits, vegetables bread, ugali, porridge and milk.
      The level of malnutrition was low with underweight at 16% stunting 4.3% and
      wasting 1.0%. The factors that positively correlated with child nutritional
      status were the age of the mother and father. CONCLUSIONS: The children were
      consuming a variety of foods both at home and in school, and this together with
      the high literacy levels the parents/guardians could have contributed towards the
      good nutritional status.

PMID- 16450681
TI  - Appendicitis at Kenyatta National Hospital, Nairobi.
AB  - BACKGROUND: Appendicitis still remains a diagnostic challenge particularly in
      women and extremes of age. The incidence of appendicectomy for suspected
      appendicitis is higher but declining in the developed countries in contrast with
      a low but increasing incidence in Africa. OBJECTIVE: To describe the
      characteristics of appendicitis at Kenyatta National Hospital, with emphasis on
      epidemiological oddities. DESIGN: A prospective descriptive study. SETTING:
      Kenyatta National Hospital, a 2000 bed teaching and referral hospital in Nairobi,
      Kenya SUBJECTS: One hundred and eighty nine patients managed for suspected acute
      appendicitis between July 2000 and June 2001. RESULTS: There were 116 males and
      73 females. The peak incidence was in the third decade. Sixty four percent of
      patients were below 30 years of age. The elderly (< 60 years of age) accounted
      for 1.6% of cases. The rate of false appendicectomy was 18.0%. This rate of
      negative appendicectomies was 12.9% for males and 30.1% for females. The rate of
      perforation/gangrene was 29.7%. Hospital stay averaged 6.4 days. Overall
      morbidity was 12.3%. It was 19.4% in perforated appendicitis and 7.6% in non
      perforated appendicitis. There was no mortality. CONCLUSION: The incidence of
      appendicitis has increased at Kenyatta National Hospital over the last 30 years.
      The disease is common in men in their third decade. These odd characteristics
      warrant further investigations.

PMID- 16450682
TI  - Comparing walk-in and call-responsive donors in a national and a private hospital
      in Nairobi.
AB  - BACKGROUND: The non-remunerated donors in many of Kenya's hospital blood banks
      are either call responsive (CR) or walk-in (WI) donors. These donors impact
      differently on the national blood transfusion services. OBJECTIVE: To examine the
      walk-in (WI) and call responsive (CR) donors' influence on the national blood
      transfusion services. DESIGN: A retrospective study. SETTING: A national referral
      and a private hospital in Nairobi, Kenya. MAIN OUTCOME MEASURES: Donor's age,
      sex, whether walk in or responded to a call to donate for a relative or emergency
      blood requirement and test results of; HIV, HBsAg, syphilis and HCV. RESULTS:
      Between April 1999 and April 2000, 10,295 persons donated blood either responding
      to a call or walked in. The national referral hospital had 8,563 (83%) and
      private hospital 1,732 (17%). In total, 2.5% were WI and 97.5% CR. The lowest age
      of donors were CR 15, and WI 18 years. Of 1,138 (11.1%) rejected were 4.6% WI and
      11.2% CR donors. The infections 5.8% HIV, 4% HBSAg, 1.2% VDRL and 0.2% HCV were
      statistically significant in WI compared to CR (p=0.002), also in female compared
      to male donors (p=0.001). CONCLUSION: This study shows that walk in donors were
      fewer than call responsive but had less rates of transfusion associated
      infections.

PMID- 16450683
TI  - Systemic ototoxicity: a review.
AB  - BACKGROUND: Systemic ototoxicity is a significant cause of vestibulocochlear
      morbidity in sub-Saharan Africa. It may result in permanent hearing impairment
      and/or balance problems. OBJECTIVES: To review the literature pertaining to the
      ototoxic potential of three frequently prescribed systemic medications in the sub
      Saharan setting; quinine, furosemide and aminoglycoside antibiotics. The
      pathophysiology, clinical manifestations and risk factors and risk minimisation
      strategies regarding the ototoxicity associated with these drugs are presented in
      order to highlight this problem and reduce the incidence of adverse outcomes.
      DATA SOURCES: The biomedical literature was systematically reviewed. This
      included a search of the National Library of Medicine's PubMed database
      (http://www.ncbi.nlm.nih.gov/ entrez/query.fcgi?db=PubMed). The search was
      limited to the English language literature and used the following search terms:
      ototoxicity; aminoglycosides; quinine; furosemide; gentamicin; vestibular
      toxicity; auditory toxicity; and Africa. STUDY SELECTION: Studies and reviews
      directly addressing clinical ototoxicity, experimental studies and studies
      regarding ototoxicity in sub-Saharan Africa were reviewed. The authors formed a
      consensus opinion regarding the most relevant articles considering factors
      including evidence level. DATA EXTRACTION: Systematic data extraction was
      undertaken from relevant studies. CONCLUSIONS: Quinine, furosemide and
      aminoglycosides are potentially ototoxic. High doses, prolonged treatment and
      intravenous administration increase this risk. The clinical condition of the
      patient may further predispose patients to ototoxic damage. Lack of monitoring
      facilities and efficacious, cost effective alternatives increase the risks of
      ototoxicity in the African setting. Clinicians must be aware of these risks and
      those patients at increased risk, and be vigilant in recognising their clinical
      manifestations.

PMID- 16450684
TI  - Gastroschisis: immediate reduction by bianchi procedure at Moi Teaching and
      Referral Hospital, Eldoret: case report.
AB  - This is a report of the only case of gastroschisis that has survived at the Moi
      Teaching and Referral Hospital in the past five years. Others, who have been
      referred to this hospital arriving occasionally without the necessary care for
      this problem in place, have not even managed to survive through the period of
      resuscitation. The objective of this report is to show that these children can
      survive. Immediate post-natal care for protruded abdominal organs, fluid
      resuscitation and adherence to the principles of neonatal transport are
      essential.

PMID- 16450685
TI  - Incidence of Brescia-Cimino arterio-venous fistula formation at the wrist level
      in chronic kidney disease patients requiring haemodialysis at Chris Hani
      Baragwanath Hospital.

PMID- 16450686
TI  - Shoehorn technique for reduction of distal radius fracture: a technical note.
AB  - We describe a minimally invasive technique for reducing a fracture of the distal
      radius after closed reduction has failed. Being able to disimpact, distract, and
      translate the distal fracture fragment--using a small, intrafocally placed
      periosteal elevator as a lever--can make formal open reduction unnecessary for
      such fractures. Soft-tissue dissection and bone devascularization can be
      minimized with use of this technique.

PMID- 16450687
TI  - Periprosthetic fractures of the humerus.
AB  - Periprosthetic humeral fractures present a treatment challenge for the orthopedic
      surgeon. The overall incidence of fracture is between 0.5% and 3%, with the
      majority of fractures occurring intraoperatively and involving the humeral
      diaphysis. Excess torque produced during surgery is usually responsible for
      intraoperative fractures. Improper canal preparation or prosthetic placement may
      also increase the chance of sustaining a fracture. Postoperative fractures are
      most commonly caused by minor trauma, such as a fall. Poor bone quality, female
      sex, advanced age, and history of rheumatoid arthritis are the risk factors most
      commonly associated with periprosthetic fractures. All 4 systems used to describe
      periprosthetic humeral shaft fractures classify fracture patterns according to
      the anatomic relation of the fracture to the prosthetic stem. Treatment decisions
      should be made with respect to obtaining fracture stability, initiating early
      gleno-humeral motion, and restoring shoulder function. Intraoperative fractures
      and any postoperative fracture resulting in prosthetic instability should be
      treated with a long-stem prosthesis extending at least 2 to 3 cortical diameters
      past the fracture site with consideration for rigid plate fixation. Short oblique
      or transverse postoperative fractures should be managed with early stable
      fixation. There has been some support for conservative treatment of long oblique
      or spiral postoperative fractures. Postoperative diaphyseal fractures distal to
      the stem generally are well maintained with standard fracture management.

PMID- 16450689
TI  - Developing a management algorithm for persistent shoulder pain.

PMID- 16450688
TI  - Tramadol/acetaminophen tablets in the treatment of postsurgical orthopedic pain.
AB  - Tramadol/acetaminophen (APAP) combination tablets were shown effective and safe
      for postsurgical orthopedic pain in a 6-day, multicenter, randomized, double
      blind, active- and placebo-controlled study. Of 305 intent-to-treat (ITT)
      postsurgical patients, 153 patients undergoing arthroscopy who had at least
      moderate pain were randomized to receive either tramadol 37.5 mg/APAP 325 mg
      (mean, 4.3 tablets), or codeine 30 mg/APAP 300 mg (mean, 4.6 tablets), or
      placebo. Tramadol/APAP was superior to placebo for the following outcome
      variables: total pain relief (TOTPAR, P = .013), sum of pain intensity
      differences (SPID, P = .049), sum of total pain relief and sum of pain intensity
      differences (SPRID, P = .018), and average daily pain relief (P = .031). Similar
      incidence of adverse events for tramadol/APAP and codeine/APAP was found, except
      for constipation (0% vs 10.9%) and vomiting (8.2% vs 16.4%).

PMID- 16450690
TI  - Persistent shoulder pain: epidemiology, pathophysiology, and diagnosis.
AB  - Persistent shoulder pain is a very common condition that often has a
      multifactorial underlying pathology and is associated with high societal cost and
      patient burden. In 2000, the direct costs for the treatment of shoulder
      dysfunction in the United States totaled $7 billion. Persistent shoulder pain can
      result from bursitis, tendinitis, rotator cuff tear, adhesive capsulitis,
      impingement syndrome, avascular necrosis, glenohumeral osteoarthritis (OA), and
      other causes of degenerative joint disease or from traumatic injury, either in
      combination or as a separate entity. Rotator cuff disorders, adhesive capsulitis,
      and glenohumeral OA are all common causes of persistent shoulder pain, accounting
      for about 10%, 6%, and 2% to 5%, respectively, of all shoulder pain. All 3
      conditions have complex etiologies, but they can be diagnosed in the majority of
      patients on the basis of medical history, focused physical examination, and plain
      film radiographs. This brief review and the following articles in this supplement
      focus on persistent shoulder pain associated with rotator cuff disorders,
      adhesive capsulitis, and glenohumeral OA.

PMID- 16450691
TI  - An overview of treatment options for persistent shoulder pain.
AB  - Persistent shoulder pain (PSP) associated with rotator cuff disorders,
      glenohumeral osteoarthritis (OA), or adhesive capsulitis is a very common, often
      difficult-to-treat condition. The first step in nonoperative therapy for PSP in
      most patients is physical therapy, rest, and use of various heat modalities.
      Relief of pain from exercises aimed at improving strength and range of motion may
      be enhanced by administration of oral analgesics. Oral nonsteroidal anti
      inflammatory drugs are often prescribed for patients with PSP, but their use may
      be complicated by gastrointestinal side effects and a potential for increased
      risk for serious cardiovascular events. Intra-articular corticosteroid injections
      have been demonstrated to provide benefit in patients with rotator cuff disorders
      and perhaps also in those with adhesive capsulitis. Results from both small-scale
      studies and a recent large-scale trial have shown that injection of sodium
      hyaluronate is also effective for the treatment of PSP, particularly in patients
      with glenohumeral OA. Additional well-controlled comparative trials are needed to
      define which treatment modalities are likely to be most effective in subsets of
      patients with PSP.

PMID- 16450692
TI  - Management of persistent shoulder pain: a treatment algorithm.
AB  - Treatment of patients with complex multifactorial diseases can be clarified by
      the development of clear, evidence-based treatment guidelines or algorithms. This
      article presents a detailed algorithm for the management of patients who present
      with persistent shoulder pain secondary to rotator cuff disorder, adhesive
      capsulitis, or glenohumeral osteoarthritis. The algorithm includes both
      nonpharmacologic and pharmacologic interventions and provides a stepwise approach
      for managing patients' care. While "treatment pathways" are set forth for these
      specific disorders, the algorithm also provides a common nonoperative protocol
      for general shoulder conditions that should help simplify patient management and
      guide clinicians to alternative therapies.

PMID- 16450693
TI  - Case management outcomes help prove your value to your hospital.

PMID- 16450694
TI  - Conferences help CMs, MDs agree on avoidable days.

PMID- 16450695
TI  - Care plans for frequent flyers save money, cut costs.

PMID- 16450697
TI  - QI experts say 'automatic' handoffs could cause errors.

PMID- 16450696
TI  - Simple acronym helps staff focus on neuro patients' needs.

PMID- 16450698
TI  - CDM analyst is 'next step' to ensure clean claim.

PMID- 16450699
TI  - Stroke program wins first Codman Award for DM.

PMID- 16450700
TI  - Pediatric cancer patients present challenges.

PMID- 16450701
TI  - Adaptation.
AB  - The term adaptation is used in biology in three different ways. It may refer to
      changes which occur at the cell and organ level, or at the individual level, or
      at the level of gene action and evolutionary processes. Adaptation by cells,
      especially nerve cells helps in: communication within the body, the
      distinguishing of stimuli, the avoidance of overload and the conservation of
      energy. The time course and complexity of these mechanisms varies. Adaptive
      characters of organisms, including adaptive behaviours, increase fitness so this
      adaptation is evolutionary. The major part of this paper concerns adaptation by
      individuals and its relationships to welfare. In complex animals, feed forward
      control is widely used. Individuals predict problems and adapt by acting before
      the environmental effect is substantial. Much of adaptation involves brain
      control and animals have a set of needs, located in the brain and acting largely
      via motivational mechanisms, to regulate life. Needs may be for resources but are
      also for actions and stimuli which are part of the mechanism which has evolved to
      obtain the resources. Hence pigs do not just need food but need to be able to
      carry out actions like rooting in earth or manipulating materials which are part
      of foraging behaviour. The welfare of an individual is its state as regards its
      attempts to cope with its environment. This state includes various adaptive
      mechanisms including feelings and those which cope with disease. The part of
      welfare which is concerned with coping with pathology is health. Disease, which
      implies some significant effect of pathology, always results in poor welfare.
      Welfare varies over a range from very good, when adaptation is effective and
      there are feelings of pleasure or contentment, to very poor. A key point
      concerning the concept of individual adaptation in relation to welfare is that
      welfare may be good or poor while adaptation is occurring. Some adaptation is
      very easy and energetically cheap and welfare can be very good when it is
      occurring. Other adaptation is difficult and may involve lower or higher level
      emergency physiological responses or abnormal behaviour, often with bad feelings
      such as pain or fear. In that case, welfare is poor or very poor even if complete
      adaptation eventually occurs and there is no long-term threat to the life of the
      individual. In some circumstances, adaptation may be unsuccessful, the individual
      is not able to cope, stress occurs and welfare is ultimately very poor.

PMID- 16450702
TI  - [Methods for transcriptome and proteome research: applications for studying the
      biology of reproduction in cattle].
AB  - Improvements of animal health, welfare and product quality are major goals of
      modern animal breeding. Thus, in addition to the classical production traits,
      functional traits such as disease resistance, fertility and longevity moved into
      the center of animal breeder's interests. Due to their low heritability, the
      improvement of functional traits using conventional approaches of phenotypic
      testing and quantitative genetics is difficult. A number of studies have been
      conducted worldwide in various species to map quantitative trait loci (QTLs) and
      to identify genetic markers for health traits. This has revealed a plethora of
      chromosome regions which may harbor genes with relevance for animal health.
      Functional genome research integrates holistic investigations at the level of the
      genome, at the level of gene activity (transcriptome, proteome) and at various
      levels of phenotypic expression. The integration of all these levels of
      information provides the basis for the functional dissection of complex traits.
      This review provides an overview of the most important strategies for holistic
      transcriptome and proteome analyses. The successful application of these
      techniques is exemplified by our studies of bovine reproductive biology.

PMID- 16450703
TI  - Effects of reduction in floor space during crating on haematological indices in
      broilers.
AB  - In the perspective of animal protection and welfare, the most common and
      potentially the most frightening events encountered by the domestic fowl are
      procedures connected with transport. This study provides an evidence that
      reduction in floor space during crating, which is approximately 10% above
      requirements given to EEC Directives (accompanied with mixed social and heat
      stress due to high animal density), induces markedly elevated stress in broilers
      which is manifested by changes in haematological indices. The experiment was
      performed on ROSS 308 broilers (total number 70, mean body weight 3.05 kg). At 42
      days of age, the broilers were crated for 2-hours either with reduction in floor
      space to 115 cm2/kg (S115) or 105 cm2/kg (S105) of body weight. The total
      erythrocyte and leukocyte count, haematocrit, haemoglobin, MCV (mean cell value),
      MCH (mean cell haemoglobin) and MCHC (mean cell haemoglobin concentration) values
      were monitored and differential leukocyte count was assessed 20 h following
      crating. When compared with uncrated control, S105 broilers exhibited highly
      significant increase in haemoglobin level, MCH and MCHC values, significant
      increase in MCV values and significant decrease in total erythrocyte count. S115
      broilers did not manifest any significant changes in haematological parameters
      compared with control. When compared with S115 broilers, S105 broilers manifested
      significantly elevated haemoglobin level and MCV values, highly significantly
      elevated MCH and MCHC values and depressed erythrocyte count. It follows from
      results that the reduction in floor space to 115 cm2/kg for 2 hours did not
      induce any significant changes in both total and differential leukocyte counts in
      blood of broilers when compared with control chickens. However, reduction in
      floor space to 105 cm2/kg resulted in highly significant increase in heterophil
      counts and subsequently also HLR (heterophil/lymphocyte ratio) was significantly
      elevated. When compared S105 and S115 broilers, mean values of heterophil counts
      and HLR ratio were higher due to reduction in floor space to 105 cm2/kg. The
      differences, however, were not statistically significant.

PMID- 16450704
TI  - [Detection of Salmonella in faecal, tissue, and feed samples by conventional
      culture methods and VIDAS Salmonella Test].
AB  - The VIDAS Salmonella Test (VST) is an enzyme-linked fluorescent immunoassay for
      the detection of Salmonella-antigens. The suitability of VST for the detection of
      Salmonella in faecal, tissue, and feed samples was evaluated by the comparison
      with routine culture methods. From 312 naturally contaminated samples 17 were
      classified as Salmonella positive by routine methods and 28 by VST. Salmonella
      were isolated from 15 VST positive samples by the routine method and from eight
      samples only by an extended culture method. Five positive VST results could not
      be proved by culture. Two samples were classified as positive by the routine
      method and as false-negative by VST. The sensitivity varied between 88% and 100%
      and the specifity between 92% and 100%, depending on the kind of sample. Matrix
      or serovar specific factors resulting in a false VST result could not be
      determined. The performance of VST was easy and did not require special
      experiences. Mostly, samples with Salmonella negative results were faster
      detected than by culture methods. VST is suitable for the detection of Salmonella
      in the studied kind of samples especially as a screening method.

PMID- 16450705
TI  - [Molecularbiological diagnosis of herpes virus infection of a juvenile Russian
      tortoise (Agrionemys horsfieldii) with skin and lung lesions].
AB  - Herpesvirus infections are significant in the care of turtles and tortoises.
      Clinical signs range from unspecific symptoms, due to the variety of organ
      manifestations, to the "classical" picture of rhinitis-stomatitis. The presented
      case study showed the typical disease only with respect to clinical symptoms
      following hibernation, but lacks stomatitis, erosions or plaques in the oral
      mucosa. On the other hand, skin lesions on the extremeties, causative with
      herpesvirus infection, could be diagnosed. In this case study, various symptoms,
      sampling procedures and diagnostics using two different PCR methods are
      presented. Following hibernation, samples from a Russian tortoise (Agrionemys
      horsfieldii) were taken ante mortem and post mortem and screened with respect to
      virology, pathology, bacteriology and parasitology. DNA-fragments specific for
      tortoise herpesvirus were detected in various organs and body liquids.
      Furthermore basophilic intranuclear inclusion bodies were found. The
      bacteriological examination showed a high level of Pasteurella testunis in the
      lungs. By parasitological examination nematodes (Oxyridae) were diagnosed. A
      potential prophylaxis tortoise herpesvirus is discussed.

PMID- 16450706
TI  - Detection of canine coronaviruses genotype I and II in raised Canidae animals in
      China.
AB  - An RT-nPCR assay was used for testing fecal samples of dogs, foxes, raccoon dogs
      and minks for the presence of canine coronavirus (CCV). The animals were raised
      in homes, dog schools or farms. Seventy out of 81 healthy dog feces from three
      cities and 21 out of 48 diarrhea feces from pet dogs were positive for type II
      CCV. From a total of 61 healthy fox feces, 43 were positive for type II and 29
      for type I CCV, out of which 25 were simultaneously positive for the two
      different genotypes. Among 24 raccoon dogs samples, 22 were CCV type II-positive,
      and from those 16 were additionally type I positive. No CCVs was detected from
      healthy mink feces. Sequence analysis found that ten type II CCVs fragments of M
      gene shared a high similarity with reference strain CCV 1-71 (96.5-99.5%), and
      four type I CCVs shared a high similarity (96.7%-98.1%) with a reported FCV-like
      CCV strain. The sequence of one particular M gene fragment was found to cluster
      between the type I and type II CCV branches in phylogenetic analysis, suggesting
      the existence of a novel strain. Our study confirmed that type II CCVs infection
      is very common in domestic dog, fox, and raccoon dog populations in China. This
      is also the first report on the co-existence of two CCV genotypes in healthy
      foxes and raccoon dogs.

PMID- 16450707
TI  - Concentration of airborne endotoxins and airborne bacteria in Chinese rabbit
      houses.
AB  - Concentration of airborne endotoxins, airborne aerobic bacteria and airborne
      aerobic gram-negative bacteria were measured in 3 rabbit houses. Further, the
      species composition of the airborne gram-negative bacterial flora was
      investigated. The total amount of airborne endotoxin ranged from 22 to 774 EU/m3
      (Endotoxin Units/m3). The number of total airborne aerobic bacteria varied
      between 780 and 20100 CFU/m3, the number of airborne aerobic gram-negative
      bacteria between 39 and 1030 CFU/m3. Most gram-negative bacterial isolates
      belonged to the family Enterobacteriaceae with E. coli as primary species. In two
      rabbit houses also airborne Pasteurella multocida spp. multocida, the most common
      respiratory pathogen of rabbits, was isolated.

PMID- 16450708
TI  - Comparison of California Mastitis Test (CMT), Somatic Cell Counts (SCC) and
      bacteriological examinations for detection of camel (Camelus dromedarius)
      mastitis in Ethiopia.
AB  - A total of 956 quarter milk samples from 253 traditionally managed lactating
      camels were collected aseptically from Negele (Borena Region), Dire Dawa, and
      Gewane (Afar Region), Ethiopia, according to multi-stage sampling. The quarter
      milk samples were subjected to California Mastitis Test (CMT), Somatic Cell
      Counts (SCC) and bacteriological examinations. Five hundred and seventy one
      (59.7%) quarter milk samples had microorganisms. Of these, 428 (75.0%) had
      isolates that were identified as major pathogens (MAP) and 143 (25.0%) as minor
      pathogens (MIP). A positive correlation was found between CMT scores and
      bacteriological classes (MAP, MIP) (p-value = 0.00). Strong correlation (p-value
      = 0.00) between CMT scores and SCC was recorded. The differences among the median
      log SCC of bacteriological classes (MAP, MIP) were not significant (p-value =
      0.24). Similarly, the application of the cut-off level of 2.5 x 10(5) ml(-1)
      indicated less agreement (p-value = 0.32) for bacteriological classes MAP and
      MIP.

PMID- 16450709
TI  - The use of Thymi Herba as feed additive (0.1%, 0.5%, 1.0%) in weanling piglets
      with assessment of the shedding of haemolysing E. coli and the detection of
      thymol in the blood plasma.
AB  - Thymi Herba (Thymus vulgaris, rubbed) was given as feed additive to weanling
      piglets. 3 concentrations (0.1%, 0.5%, 1%) were tested against a control group.
      Rectal swabs were collected weekly and were sent in for bacterial testing. The
      shedding of haemolysing E. coli was evaluated. There was no significant
      difference in the shedding of haemolysing E. coli between the 4 groups. Neither
      was there a difference in the distribution of the various serotypes. Thymol was
      detected in the blood plasma in all thyme groups. The increase in thymol level
      with greater amounts of thyme herb was significant. Three days after withdrawal
      of the feed additive no thymol levels were detected. The study results did not
      reveal any effects on haemolysing E. coli in the gut.

PMID- 16450711
TI  - [Suitability of the peroral administration of the marker creatinine for the
      quantitative determination of the glomerular filtration rate (GFR) in dogs].
AB  - Established renal function tests for the quantitative determination of the
      glomerular filtration rate (GFR) in small animals by means of an exogenous
      clearance marker like creatinine are based on the intravenous or subcutaneous
      administration of the marker. In order to simplify performing the test, the
      suitability of the peroral administration of the marker substance was tested.
      Exogenous creatinine was administered to 17 Beagle dogs successively by the
      peroral (dose: 4 g/m2 BSA) and the subcutaneous route (dose: 2 g/m2 BSA). Both
      routes were tested sequentially in fasted and fed animals. In addition to the
      peroral administration of creatinine, the absorption marker D-Xylose (dose: 0.5
      g/kg body weight) was given per os. Pharmacokinetic parameters were calculated
      based on serum concentration--time data of both markers. Maximum serum
      concentrations of the exogenous creatinine (C(max) = 1284 +/- 173 micromol/l)
      were observed 92 +/- 19 min post-dose (t(max)) in fasted dogs after peroral
      administration of creatinine. C(max) (956 +/- 209 micromol/l) and t(max) (67 +/-
      13 min) were statistically significantly reduced in fed animals. The exogenous
      plasma clearance of creatinine was about 1/3 lower in fasted animals (94 +/- 15
      ml/min/m2) than in fed ones (134 +/- 28 ml/min/m2). The apparent terminal
      disposition half-life of the exogenous creatinine showed mean values of about 170
      min (fasted) and 200 min (fed). After peroral administration of D-Xylose, fasted
      animals showed higher C(max) (3.9 +/- 0.99 mmol/l) and t(max) values (60 +/- 18
      min) than fed dogs (C(max) = 2.2 +/- 0.55 mmol/l, t(max) = 40 +/- 15 min). C(max)
      and t(max) did not differ between fed and fasted dogs after subcutaneous
      administration of creatinine. Creatinine clearance was again higher in fed (124
      +/- 12.8 ml/min/m2) than in fasted dogs (104 +/- 9.0 ml/min/m2) after
      subcutaneous administration of the marker. The terminal disposition half-live
      was, however, similar with about 130-140 min. The route of administration
      (peroral vs. subcutaneous) did not influence the calculated clearance (no
      statistical significance when p < 0.01 is required). Creatinine in a dose of 4
      g/m2 BSA can be administered by the peroral route of administration for assessing
      the GFR. For the quantitative determination of GFR standardized condition are
      required, i.e. animals have to be fasted for > or = 6 hours.

PMID- 16450710
TI  - [Autoantibodies against structures of the central nervous system in steroid
      responsive meningitis-arteriitis in dogs].
AB  - Steroid-responsive meningitis-arteriitis (SRMA) is a disease of dogs familiar in
      small animal practice for decades. A combined evaluation of IgA in serum and
      cerebrospinal fluid (CSF) is an important diagnostic tool. It is suspected that
      immunpathological mechanisms are involved in the pathogenesis of SRMA because of
      the marked response to steroids. Excessive production of IgA seems to play a
      central role and might be caused by an immune reaction to self-antigens of the
      central nervous system (CNS). To test this hypothesis, we analyzed CSF samples
      from 55 dogs with SRMA using the western blot method. After blotting canine brain
      tissue, IgA, IgM and IgG of the CSF samples were tested for their binding to CNS
      antigens. We also evaluated CSF samples from 45 dogs with other brain diseases,
      including different encephalitides and intracranial tumors, and from healthy dogs
      as controls. Positive reactions (mostly IgA) were observed in the CSF samples
      from dogs with SRMA, different encephalitides and brain tumors (a total of 8%
      positive samples). The occurrence of autoantibodies against CNS structures was
      significantly higher in the control group "other brain diseases" than in the SRMA
      group (p = 0.0135). There was no significant difference in the number of positive
      samples between dogs with SRMA and the negative control group (healthy dogs, p =
      0.1535). Despite the small number of positive samples, only dogs with abnormal
      findings in the CSF analysis also had autoantibodies in the CSF. There was no
      significant correlation between the occurrence of autoantibodies and levels of
      IgA, protein content and cell counts in the cerebrospinal fluid. However, there
      was a certain trend toward positive reactions in CSF samples with high protein
      content. The occurrence of autoantibodies in dogs with SRMA thus seems to be an
      epiphenomenona rather than the cause of the disease.

PMID- 16450712
TI  - Influence of milking technique and lactation on the bovine teat by means of
      ultrasonographic examination.
AB  - The teats of Brown Swiss and Austrian Simmental cows, divided into two groups,
      one milked by means of an automatic milking system, the other using a
      conventional milking parlour, were examined monthly by ultrasonography. Aim of
      the study was to compare the effects of two different milking machines upon the
      structures of the bovine teat canal and wall by ultrasonography and thereby
      evaluate ultrasonography as a research tool for visualisation of different
      influences on the bovine teat. Length and thickness of the teat canal and teat
      wall thickness were measured and analysed. During lactation, teat canal length
      and thickness increased in both groups, teat canal length decreased in
      conventional milked cows at the end of lactation. Shorter and narrower teat
      canals were observed in automatic milked cows. Differences between the groups in
      teat canal length and thickness were determined in early lactation. During
      lactation teat wall thickness showed a slight increase. Automatic milked cows
      displayed thinner teat walls than cows milked in the milking parlour. Teat
      morphology was influenced by the number and duration of lactations, milk yield,
      quarter of the udder and time and date of examination. It was concluded that the
      effect of the two different milking machines caused significant differences in
      bovine teat morphology and that ultrasonography proved to be an appropriate
      method for visualising influences of the milking technique on the bovine teat.

PMID- 16450713
TI  - [Effects of teat position on selected milk components of primiparous sows during
      lactation].
AB  - The composition of sow colostrum and milk from single teats were characterized in
      20 primiparous German Landrace sows at ten points throughout lactation time
      (after birth of the first piglet, and subsequently at 12 and 24 h, 3, 5, 7, 14,
      21, 28 and 35 d postpartum). In these samples contents of protein, IgG, lactose
      and fat were analyzed. In the first 3 days of lactation protein- and IgG-contents
      drastically decreased, on the other hand the levels of energy resources lactose
      and fat increased. Significant effects of the single teat and the teat pair on
      the content of protein at farrowing and 12 h later as well as on the contents of
      IgG and lactose 12 h postpartum were found. The highest contents of protein and
      IgG were analyzed in colostrum of teats in the median udder section, the
      colostrum of cranial teats had the highest content of lactose. At days 3 and 5 of
      lactation milk showed large coefficients of variation (cv) in milk composition
      from teat to teat as well as from sow to sow (intraindividual cv: protein: 22%,
      IgG: 45%, lactose: 20%, fat: 34%; interindividual cv: protein: 36%, IgG: 85%,
      lactose: 27%, fat: 47%). During lactation period the intraindividual variation of
      milk parameters was lower than the interindividual variation. Possible reasons
      for these results are discussed.

PMID- 16450714
TI  - [Plasma haptoglobin concentration in cattle with surgically corrected torsio
      uteri intrapartum].
AB  - In 26 cows with surgically corrected torsio uteri intra partum, severity of
      disease, wound healing and secondary diseases were correlated with plasma
      haptoglobin concentration. The objective of the investigation was to determine,
      if an increased plasma haptoglobin concentration indicates the severity of
      disease respectively expected wound healing disorders or secondary diseases. The
      degree of severity of disease was determined by rectally diagnosed elasticity of
      the uterus before the surgery. In the present investigation, the severity of a
      uterine torsion intra partum could not be evaluated by determining the plasma
      haptoglobin concentration. In 9 of 11 days of investigation there was no
      significant difference in the plasma haptoglobin concentration of animals with an
      elastic uterus (animals with good prognosis) in contrast to cows with tight
      uterus (patients with poor prognosis) found. The significant differences on the
      6th and 7th day post surgery are related to secondary diseases in patients with
      poor prognosis, which develop evidently earlier and form stronger. The
      correlation of all cows with--to those without secondary illnesses shows, that 10
      days post surgery patients with secondary diseases have a significant higher
      plasma haptoglobin concentration (p < 0.05) compared to animals without secondary
      illnesses. No correlations existed between plasma haptoglobin concentration and
      wound healing in the examined cattle. A postoperatively increase of haptoglobin
      indicates a higher risk of secondary illnesses and complications.

PMID- 16450715
TI  - [Treatment of gastrointestinal stromal tumors with imatinib mesylate: a center
      based study of 13 patients].
AB  - Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors, with specific
      histological characteristics. These tumors are resistant to conventional
      radiation and chemotherapy treatment and therefore, patients with unresectable or
      metastatic GIST have a poor prognosis. Imatinib, a c-kit tyrosine kinase
      inhibitor, has recently been found to be highly effective for patients with
      advanced GIST. We report on 13 consecutive patients, aged 43-78 years, treated at
      our center between the years 2001-2004. Two patients were given imatinib as
      neoadjuvant treatment and the other 11 patients were treated with palliative
      intent. Response to imatinib was evaluable in 11 out of 13 patients. Objective
      response was seen in 10 patients (91%) and included complete response in two of
      them (18%). After a follow-up of 4-33 months (median 7 months), the median time
      to tumor progression has not yet been reached. The treatment was generally well
      tolerated. The most common adverse events included edema of the periorbital and
      lower extremities. We conclude that imatinib is a safe and highly effective
      therapy for GIST patients with unresectable or metastatic disease, providing new
      hope for durable remission in these patients.

PMID- 16450716
TI  - [Brachytherapy combined with external beam radiation in localized prostate
      cancer].
AB  - BACKGROUND & RATIONALE: A combination of brachytherapy with external beam
      radiotherapy is one treatment option for localized moderately to poorly
      differentiated prostate cancer. This article presents initial Israeli experience
      with this treatment option. METHODS: In the last 6 years, 56 men were treated
      with a combination of internal brachytherapy, external beam radiation and 6
      months adjuvant hormonotherapy. All were prospectively followed while using
      validated questionnaires to assess urinary morbidity and sexual function.
      RESULTS: Treatment was well tolerated by all. None had grade 2-3 rectal
      morbidity. Mild to moderate urinary morbidity was seen in most, not different
      than seen in radiation therapy when given as monotherapy. Sexual function was
      only mildly affected. Biochemical NED (PSA based) rates albeit for a rather short
      follow-up period, were similar to those seen when utilizing other radical
      treatment options. CONCLUSIONS: Combining I125-brachytherapy with external beam
      radiation together with a short course of hormonotherapy results in acceptable
      morbidity and good biochemical outcome. This option should be offered to selected
      patients with higher grade localized prostate cancer, when other options are less
      optimal.

PMID- 16450717
TI  - [Prophylactic oophorectomy among carriers of BRCA1/2 mutations--demographic and
      pathologic data].
AB  - BACKGROUND: During the past few years, the genes BRCAI and BRCA2 were cloned.
      Mutations in each gene are responsible for the syndrome of familial breast and
      ovarian carcinoma. Among women who carry such a mutation, there is a 56%-80% life
      time risk of developing breast cancer and a 16%-60% risk of developing ovarian
      cancer. Recently, it has been proven that prophylactic mastectomy and/or
      oophorectomy might reduce such risks of developing cancer. Neither of these
      treatments offers full protection and furthermore, compliance of carriers is
      partial, considering the physical and mental consequences of such treatment.
      GOALS AND METHODS: This study describes the sociodemographic profile of 30
      healthy carriers of BRCA1/2 mutations that underwent prophylactic salpingo
      oophorectomy. We also examined the pathological specimens and point out the ratio
      of significant pathological findings, especially the presence of cancer. The
      women are being followed-up at Hadassah Medical Center, Jerusalem. RESULTS:
      Pathological examination of the ovaries and fallopian tubes of 30 healthy
      carriers of BRCA1/2 mutations who underwent prophylactic salpingo-oophorectomy
      revealed tumor in three cases (10%). Two tumors were in the ovaries and one in
      the fallopian tube. One of these tumors was in an advanced stage and two were
      small and confined to the organ. CONCLUSIONS: Based on the above results, we
      noted that salpingo-oophorectomy, despite being quite a radical preventive
      method, might offer protection for the carriers against life-threatening silently
      developing cancer. We found cancer in 10% (3) of the women, and in two of these
      cases, prophylactic salpingo-oophorectomy became the definitive treatment for a
      small occult tumor.

PMID- 16450718
TI  - [Epidemiology of transitional cell carcinoma among Israeli Arabs].
AB  - INTRODUCTION AND OBJECTIVE: Environmental, nutritional and hereditary factors are
      known to influence the epidemiology and the course of transitional cell carcinoma
      of the bladder (TCCB) and hence attribute to major ethnic and national
      differences. The focus of this study was on the characteristics of TCCB among
      Israeli Arabs who form a particular ethnic group in the Israeli population and
      were treated in our medical centers. METHODS: All the Arab patients who presented
      with TCCB between 1993-2003 to 3 medical centers (Meir, Kfar Saba; Soroka, Beer
      Sheba and Hillel Yaffe, Hadera) were included in this study. Data was collected
      retrospectively, with special attention given to epidemiological parameters, risk
      factors, and treated history of TCCB among these patients. RESULTS: Of 1638
      patients who presented with TCCB between 1993 and 2004 at those 3 medical
      centers, 100 (6.1%) were Israeli Arabs. Male to female ratio among Arabs was
      13.4:1 (93 males, 7 females). The prevalence of smoking was 91% and 14% among
      Arab men and women respectively. The mean age at presentation was 64 (22-93).
      Arab women were older than men at the time of presentation (mean age 75.7 and
      63.1 respectively). Eighty-three percent of patients presented with superficial
      TCCB and 17% were diagnosed with invasive disease: 80% of patients who presented
      with superficial TCCB did not progress during the follow-up. In 15% of the
      patients with stage Ta TCCB progressed to stage T1, while 20% of the patients
      with superficial TCCB progressed to an invasive stage. The distribution of tumor
      grades at presentation was 21%, 47% and 32% for grades 1, 2 and 3 respectively.
      CONCLUSIONS: This study demonstrates some major differences in the epidemiology
      of TCCB among Israeli Arabs in comparison to the general Jewish population. The
      male to female ratio is significantly skewed towards male predominance. The mean
      age of the Arab men at presentation with TCCB is younger in comparison to Jewish
      men as well as to Arab women. The prevalence of smoking among Arab men who
      present with TCCB is especially high. On the other hand, the treated history and
      course of TCCB among Arabs seems to follow the known figures of TCCB.
      Environmental, life style, nutritional and hereditary factors characteristic to
      the Israeli Arab population may be associated with these ethnic epidemiological
      differences.

PMID- 16450719
TI  - [Taxotere-based chemotherapy in androgen-independent prostate cancer].
AB  - OBJECTIVE: Taxotere-based chemotherapy is the only approach which has recently
      demonstrated prolongation of survival in patients with androgen-independent
      prostate cancer. This article presents our experience with this therapy. METHODS:
      Since August 1999 we treated 49 patients with Taxotere/Estramustine or
      Taxotere/Prednisone combinations. RESULTS: Biochemical response occurred in 27
      (55.1%) patients, unaffected by prior exposure to chemotherapy. Among the 32
      patients with measurable disease, 7 (21/8%) patients demonstrated partial
      response and an additional 16 (50%) patients obtained stable disease. Half of the
      patients withdrew morphine palliative therapy. The median survival of all
      patients was 12.6 months, significantly longer in patients with biochemical
      response (14.3 vs 5.4 months) and no prior chemotherapy (14.3 vs 9.1 months). The
      disease recurred equally among osseous and soft tissue sites (18 sites each
      group). The most significant toxicity was neutropenia grade 3-4 in 26 (53%)
      patients. Infection, among them one fatal, developed in 18 (37.3%) patients.
      CONCLUSIONS: Taxotere-based chemotherapy is active and tolerated in androgen
      independent prostate cancer. Heavily pretreated patients are sensitive to
      therapy. Progression occurred in bone and soft-tissue sites.

PMID- 16450721
TI  - [Metastatic testicular cancer presenting with venous thromboembolism].
AB  - Metastatic testicular cancer can be associated with a variety of complications
      due to obstruction or invasion of adjacent structures. This is a case study of 2
      patients with testicular cancer who presented with venous thromboembolism.

PMID- 16450720
TI  - [Plasma chromogranin-A (CgA)--a potential marker for diagnosis, monitoring and
      management of prostate cancer patients].
AB  - INTRODUCTION: Neuroendocrine differentiation of prostatic adenocarcinoma is a
      recognized phenomenon, which is believed to parallel tumor progression to hormone
      refractory state. Circulating CgA levels were shown to reflect neuroendocrine
      differentiation and were found to correlate with the stage and the state of
      hormone refractoriness. Hence, CgA may become a marker for diagnosis, monitoring
      and management of prostate cancer patients. PATIENTS AND METHODS: CgA level was
      measured in plasma samples which were obtained from 40 patients with prostate
      cancer, using the ELISA kit (DAKO, Glostrup-Denmark). The normal range of CgA was
      2-18, SD = 4. The normal threshold was hence set to 26 u/L calculated as upper
      normal level + 2SD. Additionally, serum levels of PSA, CEA, CA-125, CA-15.3 and
      CA-19.9 were measured at that time. Clinical data was collected from medical
      records. RESULTS: Overall, CgA was elevated in 18 patients (45%) including 25% of
      the patients with organ confined disease, 52.9% with locally advanced disease,
      71.4% of the patients with metastases, 75% of the patients with hormone
      refractory prostate cancer and 23.1% of patients with hormone sensitive disease
      (p = 0.009). Mean CgA and PSA levels among patients with elevated CgA was 100.2
      u/L (27-717) and 301 ng/ml (4.5-1450) respectively. In comparison to 18.8 u/L (14
      26) and 14.7 ng/ml (2.6-59.7) respectively, in patients with CgA within the
      normal range (p < 0.05). PSA at the time of CgA sampling did not differ among the
      two groups. CONCLUSIONS: In this study high plasma CgA levels correlated with
      known poor prognostic factors including advanced and metastatic disease at the
      time of presentation, high pretreatment PSA levels and hormone refractoriness.
      CgA levels which reflect neuroendocrine differentiation of prostatic carcinoma
      may have a diagnostic, therapeutic and prognostic role in the management of
      prostate cancer patients.

PMID- 16450722
TI  - [Medical students' reactions to their experience in oncology and its contribution
      to their training].
AB  - The need to deepen the teaching of oncology was recognized by the Sackler Faculty
      of Medicine. In 2004, a weekly short clerkship was introduced into the 6th year
      curriculum, aiming to expose students to a variety of cancer diseases and
      treatments and to internalize the comprehensive approach to the patient and his
      family by the multi-professional team. OBJECTIVES OF THE STUDY: To present
      students' reactions to their experiences in oncology in order to learn about the
      clerkship's contribution and to find ways to improve the training. MATERIAL AND
      METHODS: A questionnaire was circulated to students at the end of their
      experiences. The response rate was 87% (out of 83), of which 55% were women. The
      answers were summarized by qualitative and quantitative methods. RESULTS: The
      students perceived the change in their attitude to cancer patients as a result of
      the acquisition of knowledge and their exposure to treatments of the diseases and
      patients (75%). They highly appreciated the implementation of the patient-doctor
      relationship and the multi-disciplinary teamwork (over 50%), transforming the
      oncologist into a different physician from his colleagues (70%), and more
      optimistic as to the prognosis. Twenty-five percent of the students expressed
      their interest in becoming involved with oncology in the future. While women
      noted the behavioral aspects of oncology significantly more than men, men
      indicated a greater appreciation of the knowledge and technologies they
      encountered. No relationship was found with the occurrence of cancer in the
      students' families. CONCLUSIONS: With the growing need to deepen physicians'
      empathy with patients and their families, especially with long-term diseases and
      health problems, oncology departments were found to serve as a unique site,
      suitable for training students. This was asserted by the students' reactions to
      the clerkship, as expressed in this study. The students furthermore expressed
      their preference for broader training exposure to palliative care and pain
      relief, and increased involvement in clinical work rather than didactics.

PMID- 16450723
TI  - [The treatment options for localized prostate cancer].
AB  - Prostate cancer is a very common tumor in men. Today the disease is very often
      diagnosed early because of an elevated PSA without symptoms and the disease is
      localized to the prostate. Patients with prostate cancer can be divided into 3
      subgroups for the carcinoma: favorable, moderate, and poorly. The grouping
      depends mainly on the Gleason score of the prostate biopsy. According to the
      Gleason score, favorable cancer is up to score 6 (3 + 3), moderate score 7, and
      poor--Gleason score 8-10. The other favorable clinical factors are PSA < 10
      ng/ml, and clinical stage by DRE of T1C or T2 (no nodule or palpable nodule not
      extending beyond the prostatic capsule). The treatment options for cure when the
      prostate cancer is localized are either radical prostatectomy or radiotherapy
      (external or brachytherapy or combination). Each of these therapies has side
      effects and each has advantages and disadvantages. Sometimes the treatment choice
      is not for cure and the options are hormonal treatment or watchful waiting.
      Twenty to 30% of the patients treated for cure may fail the treatment and have
      elevation of PSA without any clinical symptoms, or signs of local recurrence or
      distant spread. Some of these patients with biochemical failure may be cured by
      salvage treatment: radiotherapy after radical prostatectomy and salvage radical
      prostatectomy or cryotherapy following failure of radiotherapy.

PMID- 16450724
TI  - [Medical students and cancer].

PMID- 16450725
TI  - [Alcohol: a risk factor for breast cancer].
AB  - A total of 53 epidemiological studies were found that investigated the
      relationship between breast cancer and the consumption of alcohol. These studies
      discovered that the risk increased with increasing alcohol consumption.
      Specifically, there was a 7% increase in risk with each 10 gr. of alcohol per
      day. Therefore, women who drink should do so at low levels, and in many cases
      this will mean drinking less.

PMID- 16450726
TI  - [Mistletoe (Viscum album) preparations: an optional drug for cancer patients?].
AB  - Extracts and preparations from the parasitic plant mistletoe (Viscum album L.)
      have been used in the treatment of cancer for decades. Mistletoe treatment for
      cancer was introduced in 1920 by Steiner and Wegman, founders of the
      Anthroposophical medical method. Today, mistletoe extracts are the most
      frequently prescribed unconventional cancer therapies in Germany, as in some
      other European countries. Full clinical data about the efficacy of the mistletoe
      preparations is still missing. The preparations are usually given as subcutaneous
      injections, but other routes of administration are also used. Numerous
      preclinical and in-vitro studies have reported immunostimulatory, cytotoxic and
      proapoptotic effects. More than 15 prospective clinical trials using mistletoe
      extracts in patients with different malignancies have been reported. In most of
      these studies the authors reported that mistletoe extracts had therapeutic
      benefit in terms of response rate, overall survival, quality of life and
      reduction in side-effects of the oncological treatment. Unfortunately, almost all
      of these reported studies had at least one major weakness that questioned their
      reliability. Side effects of the different mistletoe preparation used in human
      studies are generally minimal and non-life threatening. In the current review
      recent studies, including two phase II studies from our center, are included. In
      the future, data that will be obtained from good quality studies might facilitate
      reaching firm conclusions regarding the therapeutic benefit of mistletoe
      preparation for oncological treatment.

PMID- 16450727
TI  - [Nutrition and pharmacological treatment for prevention of prostate cancer].
AB  - Prostate cancer is the most common neoplasm and the second cause of cancer death.
      It is an excellent target for primary chemopreventive strategies for the
      following reasons: it is highly prevalent and has a long latency period, there
      are identifiable risk factors and a precursor lesion and it produces a
      biochemical marker (serum PSA) which can serve as an intermediate end point in
      chemoprevention studies. The goal of primary prevention strategies is to prevent
      development of clinical life-threatening neoplasms in asymptomatic patients with
      no evidence of clinical disease. Identification of populations at risk for
      developing cancer is the cornerstone of chemoprevention. Well-established risk
      factors for prostate cancer include African-American race, older age and family
      history. Data on diet and obesity are less clearly defined. Since high grade
      prostatic intraepithelial neoplasia (PIN) is an early predictor of prostate
      cancer, preventive strategies focusing on men with high grade PIN are being
      explored. It was demonstrated that finasteride could significantly reduce
      prostate cancer in asymptomatic men with normal PSA and no abnormalities on
      rectal examination. Elevated prostaglandin levels, and upregulation of
      cyclooxygenase-2 (COX-2) are found in prostate cancer cell lines. There is some
      epidemiologic evidence that regular use of NSAIDs, which inhibit COX-2, may be
      associated with a lower risk of prostate cancer. In the field of nutrition, data
      from prospective large-scale studies demonstrated that increased consumption of
      lycopene-rich tomato-based foods referred to a reduction in the risk for prostate
      cancer. Vitamin E was also found to reduce prostate cancer risk. Prospective data
      showed that vitamin D has an inhibitory effect on prostate cancer development
      while increased calcium consumption, independent from dietary intake, might
      increase the risk. Dietary fat intake, particularly from animal sources, may also
      increase the risk for prostate cancer. Whether this effect is strictly due to the
      already identified compounds or to other compounds, remains to be explored.
      Further study will hopefully help to establish a core set of nutritional and
      dietary factors that can positively or negatively affect prostate cancer
      development, as well as a set of pharmacologic agents that can reduce the risk of
      prostate cancer development and/or progression in selected patients.

PMID- 16450729
TI  - [Special prescriptions and financial aspects of prescribing].

PMID- 16450728
TI  - [Hematuria in children].
AB  - A symptomatic hematuria is very common in pediatrics and adolescence. In contrast
      to painless adult hematuria, the differential diagnosis and investigative
      modalities in the pediatric population is vastly different. This article presents
      the major diseases that may cause hematuria in children and suggests an
      evaluation algorithm for the pediatric urologist.

PMID- 16450730
TI  - [Avian influenza: facts versus rumors].

PMID- 16450731
TI  - [Metaanalysis of reference values in hematology].
AB  - The reference values of the most commonly used parameters in hematology were
      evaluated in a metaanalysis using practices of a group of major hospitals in
      Switzerland and in detail review of the literature. Extensive differences of the
      reference values have been noted being caused mainly by selection of different
      patient/control collectives. Whenever possible, reference values were separately
      evaluated for age, gender and race. The reported reference values approximated a
      Gauss distribution allowing for statistical evaluation accordingly. Due to recent
      standardization (ICSH and NCCLS), differences caused by instrumentation and
      preanalytics were found to be of less importance. Our presented validated
      reference values in hematology should allow for better discrimination of
      classical hematological disease entities such as an iron deficiency anemia,
      thalassemia and hemolysis.

PMID- 16450732
TI  - [Sideroblastic anemias].
AB  - Sideroblastic anemias are a heterogenous group of disorders characterized by the
      presence of sideroblasts in the bone marrow aspirate. Current classification
      schemes distinguish between diseases of the heme synthesis pathway and diseases
      of other mitochondrial pathways which can either be of primary origin (defects in
      mitochondrial DNA) or of secondary origin (defects in nuclear DNA). Although
      several distinct hereditary forms exist, sideroblastic anemias are most
      frequently acquired diseases and belong to the group of myelodysplastic syndromes
      with the propensity to develop into overt leukemia. Treatment is mainly
      supportive (vitamins, blood transfusions, cytokines) and only rarely are bone
      marrow transplantations performed. The molecular defects of a few hereditary
      forms have already been elucidated, but the genes involved in the acquired forms
      are still largely unknown.

PMID- 16450733
TI  - [Hemoglobinopathies--clinical symptoms and diagnosis of thalassemia and abnormal
      hemoglobins].
AB  - Haemoglobinopathies constitute entities that are generated by either an abnormal
      haemoglobin or thalassaemias. While abnormal haemoglobins are caused by a
      qualitative structural abnormality of the haemoglobin molecule, thalassaemias
      result by diminished synthesis of the globin chain. Due to increased immigration
      from Asia, Africa and the Mediterranean to Northern Europe, haemoglobin S,
      haemoglobin C, haemoglobin E are also encountered commonly in Switzerland, while
      other abnormal haemoglobins are rare, yet can cause clinically relevant symptoms.
      This include haemolysis, polyglobulia, cyanosis or a combination thereof
      Thalassaemia-syndroms constitute with two million affected individuals to the
      most prelevant monogenetic diseases worldwide. Due to migration into Switzerland,
      they are also found quite commonly among our patients with 10-15 per cent of all
      hypochromic, microcytic, anemia second only to iron deficiency. Importantly,
      thalassaemias and haemoglobinopathies can occur concomitantly sometimes even with
      a normal haemoglobin variant. This results in wide-spread presentations, making
      diagnosis and clinical judgement difficult. We describe in this article not only
      physiological mechanisms and clinical presentation but also propose a step-wise
      diagnostic algorithm including selective use of molecular biology methods.

PMID- 16450734
TI  - [Hereditary enzyme defects of erythrocytes: glucose-6-phosphate dehydrogenase
      deficiency and pyruvate kinase deficiency].
AB  - Possible causes for a normocytic hyperregeneratory anemia are beside an
      incomplete treatment of iron deficiency, vitamin B12 deficiency or folic acid
      deficiency notably a hemolysis. After exclusion of other causes of hemolysis like
      immune hemolytic anemias, microangiopathic hemolytic anemias and
      hemoglobinopathies, an enzyme deficiency of erythrocytes should be considered. By
      far the most common form worldwide is the Glucose-6-phosphate deficiency. In the
      most frequent variants of this disease hemolysis occurs only during stress,
      imposed for example by infection, "oxidative" drugs or after ingestion of fava
      beans. The most serious clinical complication of the Glucose-6-phosphate
      deficiency is the rarely observed neonatal icterus. Some enzyme variants can
      cause chronic hemolysis which is described as chronic nonsperocytic hemolytic
      anemia. This form of chronic anemia can also be caused by other enzyme
      deficiencies, most frequently by the Pyruvate kinase deficiency. All other
      deficiencies of glycolytic enzymes are even rarer. It should be noted that in
      some of these very rare forms neurological rather than hematological symptoms
      predominate the clinical syndrome. If there is suspicion, on the basis of
      clinical symptoms and/or familial history, diagnosis of an enzyme deficiency can
      be achieved relatively easy by measurement of the enzyme activity. Accurate
      diagnosis might be helpful in therapeutic decisions (e.g. splenectomy in certain
      forms) and it is essential for genetic counseling, since certain deficiencies are
      transmitted as autosomal recessive disorders (e.g. pyruvate kinase deficiency),
      while the most common form, the glucose-6-phosphate dehydrogenase deficiency is
      linked to the X-chromosome.

PMID- 16450735
TI  - [Red cell membrane defects].
AB  - Genetic defects of red cell membrane proteins constitute in Europe the most
      common cause of congenital hemolytic anemias. During the past decennium the
      defects and the pathogenetic mechanisms have been eludicated. Relatively simple
      hematologic tests allow for differentiation into groups with different severity
      of the disease. This allows prognostic assessment and careful risk-benefit
      evaluation for splenectomy.

PMID- 16450736
TI  - [Paroxysmal nocturnal hemoglobinuria--consequences of a missing anchor].
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematological disorder
      characterized by the clonal expansion and differentiation of a multi-potent
      hematopoietic stem cell carrying a somatic mutation in the X-linked PIG-A gene.
      As a consequence of this mutation, glycosylphosphatidylinositol (GPI)-anchored
      proteins are lacking on the surface of blood cells derived from the mutated stem
      cell. This may result clinically in hemolytic anemia and a tendency for venous
      thrombosis and serious infection. Bone marrow failure is a frequently observed
      phenomenon associated with PNH. Reliable diagnosis of PNH is currently best
      achieved by flow cytometric analysis of GPI-anchored proteins on peripheral blood
      cells. Both the clinically relevant size of the PNH clone and type of GPI
      deficiency (complete or partial) can be reproducibly determined by this method.
      Most patients will benefit from supportive measures, albeit that allogeneic
      hematopoietic stem cell transplantation is currently considered the only
      potentially curative therapy. The development of a new therapeutic monoclonal
      antibody that reduces intravascular hemolysis and progress in diagnostic flow
      cytometry using a new GPI-specific marker may provide further benefit for PNH
      patients in the future.

PMID- 16450738
TI  - [Eosinophilia].
AB  - Eosinophils normally account for only one to three percent of peripheral-blood
      leukocytes, and the upper limit of the normal range is 450 cells per cubic
      millimeter of blood. Eosinophilia occurs in a variety of disorders. The most
      common cause of eosinophilia worldwide is helminthic infections, and the most
      common cause in industrialized nations is atopic disease. The diverse causes,
      clinical signs and symptoms, the diagnostic work-up as well as the therapeutic
      strategies will be discussed in this review. The "hypereosinophilic syndrome"
      constitutes an evolving concept and is most likely the result of a clonal
      (neoplastic) disorder. A number of new therapeutic approaches for these
      conditions have been developed and will be discussed in this article.

PMID- 16450737
TI  - [Leukopenia/neutropenia].
AB  - The first step in evaluating leukopenia is the analysis of the different
      leukocyte subpopulations. The automated total blood cell count gives a first
      impression of the decreased leukocyte subtype and if erythrocytes and/or
      platelets are involved. Microscopic interpretation of the blood smear verifies
      the automated differential and allows a statement on the morphology of the
      individual cells. Differential diagnosis of the decreased leukocyte subpopulation
      is vast and in many cases leukopenia is only an epiphenomenona of a systemic
      disease. Therefore therapy is always directed towards the underlying disorder.

PMID- 16450739
TI  - [Mast cells and basophils and their disorders].
AB  - This short review gives a brief overview on recent findings about the roles of
      basophils and mast cells in acquired and innate immunity. We try to give some
      insight into the methods used to study physiologic functions of mast cells and
      basophils. We mention variations of circulating basophil numbers as an
      epiphenomenon of some internal diseases and present an update on mastocytosis.

PMID- 16450740
TI  - [Disease entities caused by or involving the mononuclear phagocyte system].
AB  - In this review article we present an overview over the different functions of the
      mononuclear phagocyte system including different celltypes, i.e. monocyte,
      macrophage, epitheloid cells, Langhans cells and different dendritic cells.
      Further, diseases in which mononuclear macrophages are directly or indirectly
      involved are discussed. The review also discusses causes of monocytosis and
      monocytopenia along with non-malignant and malignant diseases, in which the
      mononuclear phagocyte has a crucial role.

PMID- 16450741
TI  - [Erythrocyte sedimentation rate--more than an old fashion?].
AB  - The erythrocyte sedimentation rate (ESR) is a time-honored blood test, which
      assesses the degree of erythrocyte aggregation by acute phase proteins such as
      fibrinogen and immunoglobulins. Various intrinsic factors may influence the ESR,
      among them polycytemia, microcytosis or fibrinogen consumption lead to a
      decreased ESR, while anemia, macrocytosis or hypoalbuminemia lead to an increased
      ESR. The ESR still is a very valid test for the diagnosis of certain chronic
      diseases (polymyalgia, rheumatoid arthritis, multiple myeloma, septic arthritis
      and ostemyelitis) and the follow-up of certain chronic diseases (polymyalgia
      rheumatica, systemic lupus erythematodes, chronic infections, prostatic cancer,
      and Hodgkin's disease). In acute disease states and their monitoring C-reactive
      protein and eventually procalcitonin are the tests of choice. The ESR should not
      be used for screening and check-up examinations in asymptomatic patients.

PMID- 16450742
TI  - A national survey of acute cerebrovascular disease in Israel: burden, management,
      outcome and adherence to guidelines.
AB  - BACKGROUND: There are no national data on the burden and management of acute
      cerebrovascular disease in Israel. OBJECTIVES: To delineate the burden,
      characteristics, management and outcomes of hospitalized patients with acute
      cerebrovascular disease in Israel, and to examine adherence to current
      guidelines. METHODS: We prospectively performed a national survey in all 28
      hospitals in Israel admitting patients with acute cerebrovascular events (stroke
      or transient ischemic attacks) during February and March 2004. RESULTS: During
      the survey period 2174 patients were admitted with acute cerebrovascular disease
      (mean age 71 +/- 13 years, 47% women; 89% ischemic stroke or TIA, 7%
      intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of
      patients were admitted to departments of medicine and a third to neurology, of
      which only 7% were admitted to departments with a designated stroke unit. Head
      computed tomography was performed during hospitalization in 93% of patients. The
      overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%.
      Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic
      medication at hospital discharge, and among those with atrial fibrillation about
      half were prescribed warfarin. Carotid duplex was performed in 30% and any
      vascular imaging study in 36% of patients with ischemic events. The mean (+/-SD)
      length of hospital stay was 12 +/- 27 days for ICH and 8 +/- 11 days for ischemic
      stroke. Among patients with ICH, 28% died during hospitalization and 66% died or
      remained with severe disability while for ischemic stroke the corresponding rates
      were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH
      and 14% for ischemic stroke. CONCLUSIONS: This national survey demonstrates the
      high burden of acute stroke in Israel and reveals discordance between existing
      guidelines and current practice. The findings highlight important areas for which
      reorganization is imperative for patients afflicted with acute stroke.

PMID- 16450743
TI  - Effectiveness of a "doctor-helicopter" system in Japan.
AB  - BACKGROUND: In Japan, helicopters have rarely been used for emergency medical
      services. The use of helicopters not only ensures rapid evacuation but may also
      serve to provide emergency management to patients with life-threatening injuries
      in the prehospital setting. OBJECTIVES: To evaluate a Japanese helicopter-based
      emergency medical system including an onboard physician, particularly in terms of
      probability of survival. METHODS: We conducted a retrospective review of trauma
      victims, and calculated two estimates of PS--at the scene and on arrival at the
      emergency department--based on patient age, Injury Severity Score, and Revised
      Trauma Score. RESULTS: We identified trauma victims who had an ISS above 15 and
      were transported from the scene by helicopter. Excluding cardiopulmonary arrest
      at the scene, 151 cases were studied. Thirty-two patients had hemodynamic
      instability with systolic blood pressures below 90 mmHg, caused by hemorrhagic
      shock (29 cases) or obstructive shock (3 cases). Their PS values were 0.56 +/-
      0.38 in the prehospital setting and 0.65 +/- 0.38 on arrival at the ED,
      representing a significant difference (P = 0.0003). Twenty-four of these patients
      survived, reflecting successful resuscitation during prehospital and ED
      management. CONCLUSIONS: A doctor-helicopter system was shown to improve
      probability of survival for life-threatening trauma in the Japanese emergency
      medical system.

PMID- 16450744
TI  - Effect of phototherapy on cardiorespiratory activity during sleep in neonates
      with physiologic jaundice.
AB  - BACKGROUND: Phototherapy is considered the standard of care for neonatal
      jaundice. However, its short-term cardiorespiratory effects have not been studied
      thoroughly. OBJECTIVES: To assess the cardiorespiratory effect of phototherapy
      during sleep in term infants with physiologicjaundice. METHODS: We performed two
      polysomnography studies during 3 hours sleep in 10 healthy term infants with
      physiologic jaundice; each infant served as his/her own control. The first study
      was performed just prior to phototherapy and the second study during phototherapy
      24 hours later. Heart and respiratory rates, type and duration of apneas, and
      arterial oxygen saturation were analyzed during active and quiet sleep. RESULTS:
      Term infants (gestational age 38.6 +/- 1.4 weeks, birth weight 3.2 +/- 0.5 kg)
      underwent the two polysomnography studies within a short time interval and had a
      comparable bilrubin level (3.6 +/- 0.8 and 4.5 +/- 0.8 days; 14.5 +/- 1.4 and
      13.8 +/- 2.1 mg/dl, P = NS, respectively). There was no difference in sleeping
      time or the fraction of active and quiet sleep before or during phototherapy.
      During active sleep under phototherapy there was a significant decrease in
      respiratory rate and increase in heart rate (54.3 +/- 10.3 vs. 49.1 +/- 10.8
      breaths/minute, and 125.9 +/- 11.7 vs. 129.7 +/- 15.3 beats/minute, respectively,
      P < 0.05), as well as a decrease in respiratory effort in response to apnea.
      These effects were not found during quiet sleep. Phototherapy had no significant
      effect on oxygen saturation, apnea rate or periodic breathing in either sleep
      state. No clinical significant apnea or bradycardia occurred. CONCLUSIONS:
      Phototherapy affected the cardiorespiratory activity during active sleep but not
      during quiet sleep in term infants with physiologic jaundice. These effects do
      not seem to have clinical significance in "real-life" conditions.

PMID- 16450745
TI  - Does mitral valve intervention have an impact on late survival in ischemic
      cardiomyopathy?
AB  - BACKGROUND: Ischemic mitral regurgitation is associated with reduced survival
      after coronary artery bypass surgery. OBJECTIVES: To compare long-term survival
      among patients undergoing coronary surgery for reduced left ventricular function
      and severe ischemic MR in whom the valve was repaired, replaced, or no
      intervention was performed. METHODS: Eighty patients with severe left ventricular
      dysfunction and severe MR underwent coronary bypass surgery. The mean age of the
      patients was 65 years (range 42-82), and 63 (79%) were male. Sixty-three (79%)
      were in preoperative NYHA functional class III-IV (mean NYHA 3.3), and 26 (32%)
      were operated on an urgent/emergent basis. Coronary artery bypass surgery was
      performed in all patients. The mitral valve was repaired in 38 and replaced in
      14, and in 28 there was no intervention. The clinical profile was similar in the
      three groups, although patients undergoing repair were slightly younger. RESULTS:
      Operative mortality was 15% (8%, 14%, and 25% for the repair, replacement and no
      intervention respectively; not significant). Long-term follow up was 100%
      complete, for a mean of 38 months (range 2-92). Twenty-nine patients (57%) were
      in NYHA I-II (mean NYHA 2.3). Among the surgery survivors, late survival was
      improved in the repair group compared to the other groups (P < 0.05). Predictors
      for late mortality were non-repair of the mitral valve, residual MR, and stroke
      (P = 0.005). CONCLUSIONS: Patients with severe ischemic cardiomyopathy and severe
      MR undergoing coronary bypass surgery should have a mitral procedure at the time
      of surgery. Mitral valve repair offers a survival advantage as compared to
      replacement or no intervention on the valve. Patients with residual MR had the
      worst results.

PMID- 16450746
TI  - Epidemiologic characteristics of pediatric active tuberculosis among immigrants
      from high to low tuberculosis-endemic countries: the Israeli experience.
AB  - BACKGROUND: During the last decade, Israel, a country with low tuberculosis
      rates, absorbed some 900,000 new immigrants from TB-endemic countries.
      OBJECTIVES: To analyze the specific impact of our screening procedures on active
      TB among children in Israel. METHODS: We conducted a retrospective analysis of
      epidemiologic and clinical data of all children (aged 0-17) with TB notified to
      the Ministry of Health between 1990 and 1999. RESULTS: There were 479 children
      with TB (male/female ratio 1.36). Most cases (81.8%) were foreign born,
      predominantly (88.2%) immigrants from Ethiopia and, therefore, huge differences
      existed in TB incidence rates according to countries of origin. Some 80% were
      diagnosed within 3 years of arrival, mainly due to active case-finding. Pulmonary
      TB, with infiltrates on chest X-ray, was found in 49.5%. Extra-pulmonary TB sites
      were: intra-thoracic lymphadenitis (31.1%), extra-thoracic lymphadenitis (12.5%),
      bones (3.6%), pleura (1.3%), meninges (1%), and others (1%). Seventy percent had
      a tuberculin skin test reaction > or =10 mm in size. Two (non-immigrant) children
      died of TB meningitis. CONCLUSIONS: Most of the pediatric TB cases occurred in
      recent immigrants and were diagnosed within 3 years of immigration. These data
      support our policy of active case-finding among new immigrants from Ethiopia and
      extensive contact evaluation for all TB cases.

PMID- 16450747
TI  - One year maintenance of carboplatin in patients with epithelial ovarian cancer--a
      phase II study.
AB  - BACKGROUND: The 5 year survival rate in patients with advanced epithelial ovarian
      cancer is 25-40% and treatment is mainly palliative once the disease recurs.
      OBJECTIVES: To determine the time to progression, overall survival and toxicity
      of 1 year maintenance treatment with carboplatin in women with advanced EOC after
      achieving complete remission with platinum-based combination chemotherapy.
      METHODS: Twenty-two women with epithelial ovarian cancer stage III-IV previously
      treated with platinum-based combinations who had achieved complete remission
      evidenced by symptoms, pelvic examination, computerized tomography and serum CA
      125, were assigned to the study protocol consisting of: carboplatin of AUC=6,
      three cycles every 2 months, followed by two cycles once every 3 months for a
      total of five courses over 1 year. RESULTS: Median follow-up in the 22 patients
      was 83 months (range 18-133 months), median disease-free survival was 36 months
      (range 2.5-126.4, 95% confidence interval 16.39-56.34). The 5 year survival was
      59.7% with a mean overall survival of 83 months (range 18-133, 95% CI 39.11
      127.29). Eleven patients have relapsed and died, 11 are alive, 6 are still in
      complete remission, and 5 are alive with recurrent disease. Grade III-IV toxicity
      was shown in some of the patients, anemia in 9%, thrombocytopenia in 9%, fatigue
      in 4.5%, and hypersensitivity in 4.5%. CONCLUSIONS: A 1 year extension of
      treatment with a single-agent carboplatin, administered to women with advanced
      EOC who had achieved complete recovery on platinum-based chemotherapy as their
      first-line therapy, has an acceptable toxicity. The disease-free survival and
      overall survival values noted in this study are encouraging and warrant further
      investigation.

PMID- 16450748
TI  - Sibutramine as an adjuvant therapy in adolescents suffering from morbid obesity.
AB  - BACKGROUND: The prevalence of morbid obesity is increasing rapidly. Weight
      reduction is very difficult using diet restriction and physical activity alone.
      Sibutramine has been shown to be effective and safe as an adjuvant therapy to
      diet restrictions. OBJECTIVES: To describe our experience using sibutramine in
      weight reduction treatment of adolescents suffering from morbid obesity. METHODS:
      The study group comprised 20 young persons (13 females, mean age 15 years 4
      months, range 13-18 years) with morbid obesity (body mass index above the 95th
      percentile for age and/or > or =30 kg/m2) who were treated with sibutramine 10 mg
      once a day for 1 year. RESULTS: Mean BMI was 40 +/- 5.6 kg/m2 (range 30.1 - 49.5
      kg/m2) at the beginning of treatment. Most patients showed an early weight
      reduction to mean BMI 39.3 +/- 4.9 and 35.9 +/- 5.7 at 3 and 6 months
      respectively, but stopped losing weight over the next 6 months. During the follow
      up period 17 patients discontinued the treatment. The main reason for dropout was
      the slow rate of weight reduction after 6 months. Patients suffering from
      concomitant disorders (severe asthma, hypertension, sleep obstructive apnea)
      showed improvement after weight reduction. Adverse reactions from the treatment
      were transient, mild and well tolerated. CONCLUSIONS: Sibutramine may help in
      achieving weight reduction for a short period and in improving concomitant health
      problems, however its long-term effect is limited.

PMID- 16450749
TI  - Lipoid pneumonia: a preventable complication.
AB  - BACKGROUND: Lipoid pneumonia is a pneumonitis resulting from the aspiration of
      lipids, and is commonly associated with the use of mineral oil as a laxative. LP
      is relatively unfamiliar to clinicians and is probably underdiagnosed.
      OBJECTIVES: To increase physicians' awareness of LP, its diagnosis and
      prevention. METHODS: We present two illustrative cases of LP and review the
      literature. RESULTS: Two cases of LP were diagnosed within half a year in an
      internal medicine ward. Both cases were elderly patients, and LP was associated
      with the use of mineral oil as a laxative agent. Computerized tomography revealed
      bilateral low attenuation infiltrates, associated with a "crazy paving" pattern
      in one case. Sudan Black staining was diagnostic in both cases--in one on a
      transbronchial biopsy specimen, and in the other on sputum cytologic examination.
      Both patients suffered from neurologic diseases and were at risk of aspiration.
      In both cases clinical symptoms and signs continued for several months prior to
      diagnosis but resolved after the mineral oil was discontinued. CONCLUSIONS: LP
      often occurs in elderly patients who are at risk of aspiration. The condition may
      be underdiagnosed. Since in most cases mineral oil cathartics are the causative
      agent, an effort at primary prevention is indicated. It is suggested that the
      licensing of mineral oil for internal use be changed.

PMID- 16450750
TI  - Advanced glycation end products stimulate tumor necrosis factor-alpha and
      interleukin-1 beta secretion by peritoneal macrophages in patients on continuous
      ambulatory peritoneal dialysis.
AB  - BACKGROUND: Advanced glycation end products, formed by the non-enzymatic
      glycation of proteins with reducing sugars, are thought to play a pathogenetic
      role in the vascular complications of diabetes, uremia and atherosclerosis. 132
      microglobulin is a major constituent of amyloid fibrils in dialysis-related
      amyloidosis. AGE1-modified beta2m has been found in amyloid deposits of long-term
      hemodialysis patients. AGE-modified 132m has also been shown to enhance
      chemotaxis and increase tumor necrosis factor-alpha and interleukin-1 beta
      secretion by circulating and tissue monocytes/macrophages. OBJECTIVES: To
      investigate the effect of AGE-modified 132m and AGE-human serum albumin on TNF
      alpha and IL-1beta secretion by human peritoneal macrophages derived from
      patients on continuous ambulatory peritoneal dialysis. METHODS: Human PMO were
      isolated from peritoneal dialysis effluent of stable CAPD patients and were
      incubated for 24 hours with AGE-modified beta2m, beta2m, AGE-HSA, HSA or
      lipopolysaccharide. TNF-alpha or IL-1beta secretion was measured by enzyme-linked
      immunosorbent assay in cell-free culture supernatants. RESULTS: Both AGE-modified
      beta2m and AGE-HSA significantly increased TNF-alpha and IL-1beta secretion by
      human PMO in a dose-dependent manner (50-200 microg/ml). In contrast, beta2m or
      HSA had no such stimulatory effect on TNF-alpha secretion but had a small
      significant increase in IL-1beta secretion. CONCLUSIONS: AGE-modified beta2m
      promotes in vitro TNF-alpha and IL-13 secretion by human PMO of CAPD patients.
      Activation of these macrophages by AGE-modified beta2m may be a contributory
      factor to the morphologic changes and altered permeability of the peritoneal
      membrane in long-term CAPD.

PMID- 16450751
TI  - Sentinel node mapping for gastric cancer.
AB  - BACKGROUND: Sentinel lymph node mapping is the standard of care for patients with
      malignant melanoma and breast cancer. Recently, SLN mapping was introduced to the
      field of gastric cancer. OBJECTIVES: To evaluate SLN mapping in patients with
      gastric cancer. METHODS: In 43 patients with gastric cancer, open intraoperative
      subserosal dye injection in four opposing peritumoral points was used. Ten
      minutes following dye injection, stained LNs were located, marked and examined
      postoperatively from the surgical specimen. RESULTS: SLN mapping was performed in
      43 patients with gastric cancer; 782 lymph nodes were harvested and evaluated.
      SLNs were stained in 34 of the patients (79.1%) with a mean of 2.85 SLNs per
      patient. The false negative rate was 20.9%, the positive predictive value 100%,
      the negative predictive value 78.6% and the sensitivity 86.9%. CONCLUSIONS: SLN
      mapping in patients with gastric cancer is feasible and easy to perform. SLN
      mapping may mainly affect the extent of lymph node dissection, and to a lesser
      degree gastric resection. However, more data are needed.

PMID- 16450752
TI  - Immunopathophysiologic mechanisms of cystic fibrosis lung disease.
AB  - Cystic fibrosis is a life-threatening autosomal recessive disorder with a highly
      variable clinical presentation. The pathophysiology is related to the mutant
      transmembrane conductance regulator (CFTR), a chloride channel that is encoded by
      the CF single gene located on chromosome 7. The variability of the clinical
      presentations, even among patients carrying the same mutation, is extensive
      enough to justify the hypothesis that other pathophysiologic mechanisms
      participate in the evolution of the disease phenotype. Presented here are recent
      lines of research on the contributing factors to respiratory tract morbidity, as
      well as the innate defense mechanisms in the CF lungs, the cytokines and
      chemokines that influence the inflammatory processes, the antioxidative system,
      and the composition of the airways surface fluid. These studies concluded that
      the clinical presentation is determined by pathology of the CFTR as well as by
      other mechanisms, some of which are related to the CFTR functions and others to
      the products of modifier genes as well as the influence of the environment.

PMID- 16450753
TI  - On the complexity of the pulmonary microbiology in cystic fibrosis: thoughts of a
      clinician.
AB  - The pulmonary microbiology is a dominant element in cystic fibrosis and the main
      cause of death. Contemporary consensus accords an exclusive role in this to a
      single microorganism, Pseudomonas aeruginosa. The evidence convincingly shows
      that the microbiology consists of a multiplicity of species living in perpetual
      interaction and in a variety of forms--planktonic, sessile, anaerobic--and in
      organized communities as microcosms, biofilms and ecosystem. This compound
      microbiology, the essence of the pulmonary disease, is of necessity exposed to
      constant influence both from without (the air) and within (via the blood),
      leading to a perpetual state of flux with consequent impact on the clinical
      course. It is perhaps significant that to date, most or all microbiologic studies
      were probably conducted, classically, with inert instruments (glass? plastic?),
      whereas in real life the CF microbiology lives in "test-tubes" of live mucosa
      with which it maintains a permanent "cross-talk." The difference to microbial
      life between these two media may well be very important. It therefore justifies
      study and may be far-reaching in its effect. There is persuasive argument to
      strive for a novel holistic view of the totality of the complex microbiology of
      CF, and to initiate fresh concepts, strategies and methods.

PMID- 16450754
TI  - Protein Z and its role in venous and arterial thrombosis.

PMID- 16450755
TI  - Civilian use of helicopters improves access to trauma care and increases chances
      of survival.

PMID- 16450756
TI  - Cystic fibrosis lung disease: interplay of a microbial microcosm and extremes of
      inflammation.

PMID- 16450758
TI  - Adult stem cells for neuronal repair.

PMID- 16450757
TI  - Regenerative medicine and stem cell therapy.

PMID- 16450759
TI  - An intraocular injury from a dog bite.

PMID- 16450761
TI  - The evolution of infantile pyloric stenosis.

PMID- 16450760
TI  - Atypical presentation of acute myocardial infarction in a young man diagnosed by
      multidetector computed tomography.

PMID- 16450762
TI  - Exertion dyspnea and stridor: an unusual presentation of localized laryngeal
      amyloidosis.

PMID- 16450763
TI  - Imagring silent type A aortic dissection.

PMID- 16450764
TI  - Quality of diabetes care in the community.

PMID- 16450765
TI  - Quality of diabetes care in the community.

PMID- 16450766
TI  - CAM--what is alternative and what is complementary?

PMID- 16450768
TI  - Current opinions in sialolithiasis diagnosis and treatment.
AB  - The introduction, 15 years ago, of extracorporeal shock wave lithotripsy in the
      treatment of salivary gland calculi, has changed the therapeutic approach in
      these patients. Aim of this study was to evaluate the efficacy of lithotripsy in
      sialolithiasis, after 10 years follow-up. A review has been made of the
      literature to establish current opinions in diagnosis and treatment of
      sialolithiasis. The role of ultrasonography, radiography and, in particular, of
      sialomagnetic resonance imaging in diagnosis of salivary lithiasis has been
      evaluated. The greater efficiency of the extracorporeal shock wave lithotripsy
      treatment for parotid, compared to submandibular calculi, has been demonstrated
      (57% versus 33%). In 68% of our patients, lithotripsy was resolutive after 10
      years. Ultrasonograpy should be considered first choice examination in diagnosis
      of salivary calculi. Sialo-magnetic resonance imaging is a recent, non-invasive
      diagnostic procedure with the advantage of no radiation exposure, and with better
      definition of anatomical and functional state of glandular parenchyma and duct,
      compared to other available techniques.

PMID- 16450769
TI  - Role of electron microscopy in diagnosis of parotid tumours.

PMID- 16450767
TI  - Sjogren's syndrome: an autoimmune disorder with otolaryngological involvement.
AB  - Sjorgen's syndrome (SS) is an autoimmune exocrinopathy characterized by
      lymphocyte infiltration of salivary and lacrimal glands that leads to progressive
      xerostomia and xerophtalmia. One-third of patients suffer of systemic
      manifestations including arthritis, fever, fatigue and mucosal dryness whereas
      those with major salivary involvement show an increased risk to develop low-grade
      non-Hpdgkin lymphomas. In addition, a minority of patients show symptoms related
      to progressive hearing loss whose pathogenesis remains undefined. Both deposition
      of autoantibodies to antigens of the inner-ear structures and infiltration by
      autoreactive T-cells have been implicated in its pathogenesis. In this context,
      high levels of autoantibodies to both cardiolipin and M3 muscarinic receprtors as
      well as to ciliar epitopes of the cochlear cells have been recently described.
      Here we review recent advances on the pathodgenesis of SS with a particular focus
      to otolaryngological manifestations.

PMID- 16450770
TI  - Genetic expression profiling of parotid neoplasms by cDNA microarrays.
AB  - Differentially expressed genes in various benign and malignant salivary gland
      tumours were identified by use of cDNA microarrays containing 19,000 human
      expressed sequence tags. Samples were derived from 5 patients with pleomorphic
      adenoma, 4 with Warthin's tumour, one with clear cell carcinoma, and 2 with
      mucoepidermoid carcinoma. Tumours were classified by using a subset of 486 genes.
      Benign Warthin's tumour and pleomorphic adenoma showed very distinctive gene
      expression patterns. A total of 133 genes differentiated the single malignant
      clear cell carcinoma from non-tumour salivary glands (p < 0.01), whereas only 16
      genes separated it from the highly related benign pleomorphic adenoma (p < 0.01).
      A total of 57 cDNAs were associated with mucoepidermoid carcinoma (p < 0.01). The
      results show gene expression alterations common to all tumours and unique to each
      benign and malignant tumour. The numerous Expressed Sequence Tags of unknown
      function we identified could also become useful as tumour markers and represent a
      set of novel tumour-associated genes.

PMID- 16450771
TI  - Prognostic relevance of cell proliferation in major salivary gland carcinomas.
AB  - Several proliferation markers, such as DNA ploidy, Ki67, MiB1 and proliferating
      cell nuclear antigen have been shown to correlate with clinical course and
      prognosis in several epithelial tumours and lymphomas. In the present study, the
      prognostic relevance of these markers was evaluated in major salivary gland
      carcinomas. A sample of 36 cases out of 85 patients submitted to surgery for
      major salivary gland carcinomas at our institution between 1987 and 1997 were
      studied. The sample comprised 8 adenoid-cystic carcinomas, 6 ductal carcinomas,
      11 mucoepidermoid carcinomas and 11 acinic cell carcinomas. Follow-up ranged from
      1 to 12 years (mean 6.2). In some patients, DNA ploidy (euploid or aneuploid) was
      studied by flow cytometry. In others, proliferation activity was studied by means
      of monoclonal antibody MiB1, identifying cells in the proliferative cycle. In
      some patients, both techniques were used. Follow-up was related to these indices,
      TNM and stage. Even if ploidy suggested a favourable outcome in diploid cancer
      (13 favourable vs. 2 unfavourable) and poor outcome in aneuploid cancer (4
      favourable vs. 5 unfavourable), the difference was not statistically significant
      with p = 0.06 in Fisher's exact test. Instead, the proliferative tumour cell
      fraction, evaluated by MiB1, was statistically correlated with prognosis.
      Comparing survival curves by Log rank Test it yielded p = 0.007 using an MiB1 cut
      off of 5. Applying a cut-off of 20 yielded p = 0.001. Of particular interest were
      MiB1 values in acinic cell carcinomas for which grading is challenging and lacks
      consensus. In our group of acinic cell carcinomas, survival correlated with
      values of MiB1 > or < 15 with p = 0.009 in Log rank test. In conclusion, despite
      a trend towards correlation between ploidy and prognosis, the present study
      yielded p = 0.06, whereas the proliferative fraction assessed by MiB1 was
      significantly correlated with outcomes. Indeed, "growth fraction" in acinic cell
      carcinomas may stratify different classes of risk.

PMID- 16450772
TI  - Extended parotidectomy.
AB  - Malignant tumours of the parotid gland represent a group of relatively rare
      lesions. The medical records of 363 patients with parotid swelling treated
      between 1974 and 2003 at the "G. Ferreri" Department of Otorhinolaryngology, "La
      Sapienza" University in Rome were retrospectively analysed. Clinical
      presentation, pre-operative investigations, surgical procedure, histopathology
      report, post-operative complications, and the oncological results of 19 patients
      who underwent extended radical parotidectomy for malignant neoplasm of the
      parotid gland are discussed. Extended radical parotidectomy, reserved for
      neoplasms in an advanced stage, involves the removal of the entire parotid gland,
      with sacrifice of the facial nerve and the resection en bloc of the adjacent
      structures affected by neoplastic infiltration, such as the temporal bone, the
      mandibular bone, the skin, blood vessels and nerves. In addition to this surgical
      treatment, a cycle of adjuvant radiotherapy is also necessary. The overall rate
      of survival at 10 years depends mainly on the histological characteristics of the
      tumour, and, in this series, is reported to be approximately 58%. These data
      indicate that total extended radical parotidectomy combined with post-operative
      radiotherapy, represents the best therapeutic approach with regard both to
      quality of life and life expectancy, in patients with an advanced stage of
      malignant neoplasm of the parotid gland.

PMID- 16450773
TI  - Treatment of complications of parotid gland surgery.
AB  - Although several reports in the literature have documented the surgical
      technique, and the oncological outcome achieved with parotidectomy, only a few
      articles have described the complications of parotid gland surgery and their
      management. Several complications have been reported in parotid surgery. We re
      classified the complications of parotidectomy in intra-operative and post
      operative (early and late). The commonest complications after parotidectomy are
      temporary or permanent facial palsy and Frey's syndrome.

PMID- 16450774
TI  - Current role of chemotherapy in exclusive and integrated treatment of malignant
      tumours of salivary glands.
AB  - In the management of salivary glands carcinomas, surgery is the treatment of
      choice. Post-operative radiotherapy is indicated in cases with high risk of loco
      regional relapse. Radiotherapy is also standard treatment in cases that are
      inoperable at onset. Chemotherapy plays a palliative role. Today, the integration
      between radiotherapy and chemotherapy, which provides increased local control,
      represents a significant step forward. This integration is important since 5-year
      survival in tumours with high grade histology is approximately 50%. Overall
      incidence of metastases is approximately 25%. Primary locations of metastases are
      lungs, liver, bone, central nervous system and other organs. In cases of
      metastatic disease, chemotherapy plays only a palliative role.

PMID- 16450775
TI  - Major salivary gland diseases. Multicentre study.
AB  - This multicentre study involved 28 Italian ORL Centres responding to a
      questionnaire sent by us which allowed recruitment of a high large number of
      cases of parotid neoplasms observed over a 10-year period. Statistical data
      obtained partly confirmed previous findings. Benign tumours account for 80% of
      case histories with a relationship 1:4 M/F, the most frequent being pleomorphic
      adenoma (57.3% of cases), followed by Warthin's tumour (32.4%), this rating not
      having been confirmed in case histories (8-10%) in the literature. Malignant
      tumours instead were fewer in number compared to the literature (14% vs 25-30%);
      the most frequent being mucoepidermoid carcinoma (18.2%) of which 44% G1, 33% G2
      and 23% G3. Adenoid-cystic carcinoma was observed in 15.3% and < or = 10% for all
      the other most frequent histological malignant neoplasms. Diagnostic work-up
      included echotomography and fine-needle aspiration biopsy, less used imaging
      techniques were computed tomography, magnetic resonance imaging, Sialo-computed
      tomography. During this multicentre investigation more widespread use of imaging
      techniques has, however, been observed. The greater use of ecotomography and of
      fine-needle aspiration biopsy was due to simplicity of application and low cost
      offering good sensitivity and specificity. Surgical treatment of benign tumours
      consisted, in 50% of cases, in superficial paroditectomy and in approximately 30%
      of total paroditectomy. Enucleoresection was limited to approximately 15% of
      neoplasms, enucleation to <10% of cases with only 2% of pleomorph adenoma due to
      the well-known anatomo-pathological characteristics which may lead to relapse.
      For malignant neoplasms, total parotidectomy was performed in approximately 50%
      of cases, while in the remaining 50% an almost equal rate of superficial
      parotidectomy was carried out and enlarged parotidectomy, with or without
      sacrificing the facial nerve, which was rebuilt in 60% of cases. The lateral neck
      dissection most frequently carried out was of functional type in 54% and
      selective type in 46% with removal of levels I-III and II-IV in approximately 60%
      of cases. Sentinel lymph node was observed in a limited number of centres. When
      no clinically evident lymph nodes were present (NO) considering the tumour
      histotype, two thirds of patients underwent surgery or radiotherapy, while in the
      remainder the wait-and-see attitude was prefered. Post-operative-complementary
      radiotherapy was very frequently performed instead of chemotherapy. Oncological
      results obtained were compared with those reported in the literature: in fact for
      all benign neoplasms relapse ratings are about 5%, while for malignant tumours
      the worst prognosis was in squamous cell carcinoma with median of 37.7 on
      survival and metastasis rate of 16.5%. Finally, mucoepidermoid carcinoma tumours
      showed best survival, followed by adenoid-cystic carcinoma with ranges,
      respectively, 83 and 81.

PMID- 16450776
TI  - Schwannoma of cervical sympathetic chain: assessment and management.
AB  - Schwannoma arising from the cervical sympathetic chain is an uncommon benign
      nerve tumour. This tumour most often presents as an asymptomatic solitary neck
      mass, with slow-growing and rare malignant degeneration. Definitive pre-operative
      diagnosis may be difficult and investigations are not usually helpful. The
      carotid artery and internal jugular vein may be displaced anterior-laterally.
      Diagnosis relies on clinical suspicion and confirmation is often obtained by
      means of surgical pathology. Surgical excision is the treatment of choice for
      this tumour, with recurrence being rare. Homer's syndrome is a common post
      operative neurological consequence, but does not appear to cause problems to the
      patient. The case is described of a 42-year-old male who presented an
      asymptomatic left neck mass. Diagnostic studies included computed tomography,
      magnetic resonance imaging, and ultrasound which confirmed a circumscribed mass
      in the upper left portion of the neck next to the thyroid gland. The mass was
      excised through a transverse left cervical skin incision. Post-operatively the
      patient showed clinical findings of Horner's syndrome. The pathologic and
      radiological evaluations, treatment and postoperative complications of this
      neoplasm are discussed.

PMID- 16450777
TI  - Maxillo-ethmoidal chloroma in acute myeloid leukaemia: case report.
AB  - Chloroma, also called Granulocytic Sarcoma or Myeloid Sarcoma, is a rare
      malignant extra-medullary neoplasm of myeloid precursor cells. It is usually
      associated with myelo-proliferative disorders but its appearance may precede the
      onset of leukaemia. Chloroma may be found in several extracranial sites.
      Involvement of the head and neck region is uncommon. Differential diagnosis is
      often difficult and includes acute lymphoblastic leukaemia, large cell NHL,
      lymphoblastic lymphoma and Ewing's sarcoma. The case is presented of a maxillo
      ethmoidal chloroma occurring in a case of poor prognosis acute myeloid leukaemia,
      emphasizing the clinical and cyto-histological features and problems concerning
      differential diagnosis.

PMID- 16450778
TI  - The crisis of measles and the need to expand the ways of delivering vaccines in
      Papua New Guinea.

PMID- 16450779
TI  - Neonatal outcome at Modilon Hospital, Madang: a 5-year review.
AB  - An audit of neonatal care at Modilon Hospital, Madang was performed using
      obstetric and neonatal data for the five years 1995-1999. The overall perinatal
      mortality rate (PNMR) was 51.1 per 1000 total births with an early neonatal
      mortality rate (ENNMR) of 12.7 and a stillbirth rate (SBR) of 38.5. 839 neonates
      aged 0-28 days were admitted to the Special Care Nursery. The male to female
      ratio was 1.3:1. 186 babies (22%) died. The case fatality rate was higher in
      males than females (p<0.001). Babies born at health centres or born before
      arrival had a significantly higher fatality rate than hospital-born babies
      (p<0.001). The case fatality rate was highest in babies born preterm and declined
      with increasing birthweight from less than 1000 to 3999 g. The major recorded
      causes of admission were neonatal sepsis, prematurity, neonatal jaundice, birth
      asphyxia, respiratory distress and meconium aspiration syndrome. 60% of deaths
      occurred within 48 hours of admission, 32% between 48 hours and 7 days and 8% at
      7 days or older. The proportion of deaths occurring during the afternoon and
      night shifts was significantly higher than that during the morning shift
      (p<0.001). This was most likely to be related to staffing levels. The major
      causes of death were prematurity or low birthweight (27%), sepsis (23%) and birth
      asphyxia (17%). Other causes of death included congenital abnormalities, meconium
      aspiration and meningitis. Antenatal care is still not universally available for
      Papua New Guinean women. Home delivery of high-risk mothers is commonplace, and
      women delivering in hospital often present in established labour. Perinatal and
      neonatal problems are therefore frequent. Newborn babies have the right to the
      best available care. This can only be provided if hospitals and health facilities
      understand the basic requirements of neonatal care and provide designated space,
      adequate staffing and proper equipment.

PMID- 16450780
TI  - The epidemiology of malaria in the Papua New Guinea highlands: 1. Western
      Highlands Province.
AB  - Despite a resurgence of malaria in many Papua New Guinea highlands and highlands
      fringe areas after the cessation of control activities in the early 1980s the
      malaria situation in these areas has received little attention. A series of cross
      sectional surveys were therefore carried out to provide accurate and up-to-date
      information on the prevalence of malaria and the risk of epidemics and to propose
      adequate malaria control strategies. Studies in 24 villages in Western Highlands
      Province found the prevalence of malarial infections to be strongly correlated
      with altitude, ranging from 1.6% at altitudes of 1500-1800 m to over 30% in
      villages below 900 m. Malaria outbreaks were observed at the end of the rainy
      season. All four human malaria species were present with P. falciparum infections
      clearly dominating. The relative importance of P. vivax increased with altitude,
      while both P. malariae and P. ovale were rare. Many infections were of low
      density. While malaria is an important source of febrile illness in endemic areas
      below 1500 m altitude, only few observed or reported fevers are due to malarial
      infections in higher, nonendemic areas. Rates of enlarged spleens, mean
      haemoglobin levels and the prevalence of anaemia (Hb <7.5 g/dl) were strongly
      linked to the level of malaria found in each community and were associated with
      both altitude and concurrent malarial infection. Based on the survey results,
      areas of different malaria epidemiology are delineated and options for control in
      each area are discussed.

PMID- 16450781
TI  - Antepartum prediction of respiratory distress syndrome: a comparison of the shake
      test, the tap test and the turbidity test.
AB  - The shake test, the tap test and the turbidity test were evaluated to determine
      their accuracy in predicting lung function maturity, ie their ability to predict
      respiratory distress syndrome (RDS). The turbidity test was the most efficient
      with a sensitivity of 60%, a specificity of 97%, a positive predictive value of
      82% and a negative predictive value of 92%. The shake test had a sensitivity of
      40%, a specificity of 95%, a positive predictive value of 63% and a negative
      predictive value of 88%. The tap test at 2 minutes had a sensitivity of 57%, a
      specificity of 78%, a positive predictive value of 35% and a negative predictive
      value of 89%. It was fortuitous that the simplest and cheapest test was found to
      be the most efficient test of the three. We recommend that the turbidity test or
      at least one of these tests should be used to determine the maturity of lung
      function when non-urgent elective deliveries are contemplated, to help reduce the
      incidence of RDS in this group of patients.

PMID- 16450782
TI  - Gastroschisis management: an experience in Angau Memorial Hospital.
AB  - This paper is the report of a 2 kg baby girl born with a large gastroschisis at
      the Angau Memorial Hospital. She is the first long-term survivor in Papua New
      Guinea with this major ventral abdominal wall defect as far as we are aware. In
      the report important steps in the management of this major congenital defect are
      highlighted from both the surgical and anaesthetic perspectives. It is imperative
      that a large gastroschisis be managed by a reduction carried out over two or more
      stages to prevent catastrophic abdominal compartment syndrome. Postoperative
      ventilation via an endotracheal tube was required due to respiratory compromise
      from the raised intra-abdominal pressure. Deflation of the dilated small bowel
      was shown to be an important step to allow full return of the small bowel into
      the abdominal cavity. A percutaneous jejunostomy feeding tube was inserted for
      feeding postoperatively as total parenteral nutrition was not available, and this
      was crucial for the nutritional management and ultimate survival of the baby.
      Gastroschisis is a very significant congenital defect with major challenges in
      its management in a developing country, but if important principles of management
      are followed, the prognosis can be remarkably improved.

PMID- 16450783
TI  - The assessment of patients' waiting and nursing consultation times at urban
      clinics in the National Capital District, Papua New Guinea.
AB  - This study was conducted in the National Capital District during the months of
      August, September and October 2000. The study sites were the 3 urban clinics
      situated in the suburbs of Six Mile, Hohola and Konedobu. The aim of the study
      was to determine the patients' waiting times and nursing consultation times in
      the urban clinics. A total of 1075 patients were surveyed, including 264 children
      under 5 years of age. 58% of patients were males. 24% of patients were able to
      see a nurse within 30 minutes and 70% within 2 hours. 47% had to wait 1-3 hours
      to see a consulting nurse and a further 9.5% had to wait 3-5 hours. 67% of
      nursing consultations were 5 minutes or less, which is too short to interview,
      examine and prescribe treatment for the patients and to use the Paediatric 10
      Steps. The short consultations of 5 minutes or less did not involve children
      under 5 years of age. There were only one to two nurses seeing the patients when
      79% of patients were seen. This explains why the patients' waiting time was long.
      After consultations many patients (71%) were able to get their treatment within
      30 minutes but 28% had to wait from 30 minutes to 2 hours for their treatment.
      The small number of nurses giving treatment leads to long waiting times. From the
      time of entry to exit out of the clinic, only 11% of patients spent 30 minutes or
      less in the clinic while 51% spent between 1 and 3 hours. The patients' waiting
      times and the short nursing consultation times are directly related to the
      insufficient number of nursing officers working in the clinics.

PMID- 16450785
TI  - Towards a method for informing the planning of community-based rehabilitation in
      Papua New Guinea.
AB  - Disability is a major public health problem, particularly in developing
      countries, where there is a close link between poverty and disability. The
      complex nature of disability allows it to be addressed from a number of different
      perspectives. Community-based rehabilitation (CBR) is a holistic approach towards
      disability which is currently being supported in many parts of the world,
      including Papua New Guinea (PNG). Unfortunately CBR is frequently implemented in
      resource-poor contexts, which limits the scope for research. As a result little
      effort is put into determining a need before CBR programs are established, or
      into evaluating CBR programs following implementation. This research in the
      Middle Ramu, Madang Province, tested a method for acquiring information for the
      purposes of CBR planning in PNG. The method used an adapted form of the Ten
      Questions Screen for Childhood Disability. Quantitative and qualitative methods
      were further utilized to determine the types of disability presenting, the
      biomedical and perceived causes of the various disabilities, help-seeking
      behaviours, the disabled individual's participation in village activities, and
      the needs of both disabled individuals and their caregivers. A total of 158
      disabled individuals were identified in a population of 4946 people and 20 in
      depth interviews were conducted. The data obtained were analyzed to formulate an
      appropriate 'CBR package' that would cater for the specific needs of this
      population in the Middle Ramu. Evaluation of the basic survey method revealed
      that it was more sensitive than other methods previously tried in PNG, with an
      overall disability prevalence of 3.2% obtained. Qualitative methods allowed the
      fieldworkers to get a much deeper insight into the feelings and perceptions of
      disabled individuals. The methods tested for this research in the Middle Ramu
      could have application for CBR workers in other parts of PNG.

PMID- 16450784
TI  - Survey of rickettsial antibodies at two local sites and review of rickettsiosis
      in Papua New Guinea.
AB  - The status of rickettsial infection in Papua New Guinea (PNG) is unknown although
      several reports of typhus-like illnesses infecting predominantly white settlers
      and the Allied troops during World War 2 were published between 1930 and 1945. We
      performed a serological survey for evidence of rickettsial infection by measuring
      rickettsia-specific antibody levels in the blood of 191 non-randomly selected
      Papua New Guineans living in Port Moresby (n=93) and in the highland villages of
      Samberigi (n=98). Antibodies were measured by a microimmunofluorescence method
      using a panel of rickettsial antigens of a number of species and strains. In
      addition, we have reviewed the current status of rickettsiosis in PNG. Overall,
      we were able to demonstrate significant titres of antibodies to two groups of
      rickettsiae, the scrub typhus group (STG) and the spotted fever group (SFG). All
      positive individuals (7/191) were residents of Port Moresby. None from the
      highlands showed any significant levels of antibodies to rickettsiae. The strains
      detected within each group were Gilliam and Karp for STG and, for SFG, Rickettsia
      honei, R. conorii, R. sibirica, R. rickettsii, R. australis and R. akari. No
      significant antibody titres to typhus group infection were detected in either
      Port Moresby or highland volunteers. These findings were not surprising given
      previous reports of typhus-like illnesses and favourable environmental
      characteristics for rickettsiae in some parts of PNG. Until a definite status of
      this disease is known, we suggest that rickettsial infection be included as a
      differential diagnosis for patients presenting with acute febrile illness in Port
      Moresby and surrounding areas.

PMID- 16450787
TI  - Immunohistochemical markers in the evaluation of tumors of the urinary bladder: a
      review.
AB  - The clinical utility of immunohistochemistry in the diagnosis of tumors of the
      urinary bladder is well established. With recent advances in molecular biology
      and novel technologies, several biomarkers have emerged as important adjuncts in
      the diagnosis of lesions of the bladder. When used in conjunction with careful
      histologic examination, immunohistochemistry can be a valuable aid in classifying
      adenocarcinoma presenting in the bladder and mesenchymal lesions of the bladder
      and in establishing the urothelial origin of a metastatic tumor. In addition, a
      number of biomarkers may prove to be important indicators of prognosis or
      response to chemotherapy.

PMID- 16450786
TI  - Hospital twinning between Australia and Papua New Guinea.
AB  - This brief paper presents an argument for the establishment of permanent twinning
      relationships between hospitals in Australia and Papua New Guinea as one way of
      expressing the advantages of expanding globalization while countering its
      disadvantages for human health, especially in poorer countries. This particular
      suggestion is based on the general argument that widespread and sustainable
      improvement in people's health will be more likely to occur if health
      professionals take action themselves and work directly with each other. Disease
      does not respect national borders. Therefore, professional solidarity must be
      international, and strengthening the global health sector will amplify its
      benefits to human health, now and in the future. The particular suggestion that
      is made here is but one small step in this direction, but should have immediate
      benefit to those involved.

PMID- 16450788
TI  - A systematic approach to identifying urothelial cells likely to be polysomic by
      fluorescence in situ hybridization.
AB  - OBJECTIVE: To determine which nuclear morphologic and background features are
      most associated with normal and abnormal chromosome patterns in urine cells
      evaluated by fluorescence in situ hybridization (FISH) with Vysis UroVysion
      (Downers Grove, Illinois, USA). STUDY DESIGN: One hundred specimens were analyzed
      and the nuclear morphologic and background features compared between FISH
      negative (disomic) and -positive (polysomic) cases. RESULTS: Our data show that
      polysomic urothelial cells have significantly (p < 0.001) weaker DAPI nuclear
      counterstaining, nuclear enlargement, more irregular nuclear shape and more
      chromatin clumping when compared to disomic cells. CONCLUSION: These findings
      indicate that there are specific staining and nuclear cytologic features that can
      help identify cells that have a high probability of being polysomic by FISH. This
      information may help cytologists decrease the time required to evaluate urine
      specimens by FISH and may aid in the development of instruments that automate
      FISH analysis.

PMID- 16450789
TI  - The evolution of scanning microphotometry: a historical review.
AB  - This article traces the evolution of scanning microphotometry from its beginning,
      with an emphasis on the developing technologies that have made feasible the rapid
      and detailed capture of high-resolution image information. Consideration is given
      to future directions that may prove fruitful to clinical practice.

PMID- 16450791
TI  - What makes a good doctor?

PMID- 16450790
TI  - AgNOR counts in cervical smears under normal and other cytopathologic conditions.
AB  - OBJECTIVE: To investigate the diagnostic value of AgNOR counts in cervical smears
      in the process of cervical carcinogenesis and in discriminating the different
      grades of squamous intraepithelial lesion (SIL). STUDY DESIGN: Silver nitrate
      staining for AgNOR counts was performed in 50 cervical smears of cytologically
      diagnosed normal, inflammatory, low grade SIL (LSIL) (mild dysplasia), high grade
      SIL (HSIL) (moderate and severe dysplasia) and squamous cell carcinoma. The
      smears were derived from the ongoing routine outpatient cytology screening at
      Queen Mary's Hospital, Lucknow, India. RESULTS: In normal and inflammatory
      smears, the number of AgNOR dots varied from 1 to 2, in mild dysplasia from 2 to
      4, in moderate dysplasia from 4 to 6 and in severe dysplasia from 6 to 8. Frank
      cervical carcinoma cases revealed 8-10 dots. Thus, a progressive increase in
      AgNOR counts was observed when the severity of pathologic lesions increased.
      Statistical analysis revealed a significant difference in AgNOR counts between
      normal and inflammatory smears, but it was highly significant between
      inflammatory and LSIL cases, between LSIL and HSIL, and between severe dysplasia
      and frank malignancy. CONCLUSION: This study underscored the diagnostic
      importance of AgNOR counts, especially in discriminating between LSIL and HSIL of
      the cervix. Another study is under way to assess the potentiality of AgNOR counts
      as tumor markers in cervical carcinogenesis.

PMID- 16450792
TI  - The benefits of statin therapy--what questions remain?
AB  - Early hydroxymethylglutaryl-CoA reductase inhibitor (statin) trials provided the
      first evidence of the benefits of statin therapy in secondary prevention of
      coronary heart disease (CHD). Outcomes data from more recent trials involving
      atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin, have since
      expanded the patient population shown to benefit from statin therapy. Current
      studies are evaluating the benefits of lowering lipid levels with statins to
      below current goals, as well as examining benefits in special patient populations
      and evaluating the value of surrogate markers of CHD. Early trials provided a
      solid foundation of knowledge on the efficacy and safety of statins. Recent and
      ongoing trials generate new data to resolve remaining questions in the fields of
      CHD prevention and lipidology.

PMID- 16450793
TI  - Coronary angiography of cardiac myxoma.
AB  - BACKGROUND: Myxoma usually presents with nonspecific symptoms. Preoperative
      coronary angiography is presently only considered if patients are at increased
      risk of coronary artery disease (CAD). The angiographic patterns of cardiac
      myxoma have not been fully described. HYPOTHESIS: The aim of our study was to
      investigate coronary angiograms as well as patterns of tumor vascularity in
      patients with cardiac myxoma. METHODS: From January 1990 to December 2003, 33
      patients with cardiac myxoma, who had received surgical resection at our
      hospital, were enrolled; of these, 9 patients underwent preoperative coronary
      angiography. The severity and extent of coronary artery stenosis, as well as
      tumor angiographic patterns, were analyzed. Coronary artery disease is defined as
      a > 50% stenosis in diameter at any segment of the coronary artery viewed by two
      orthogonal views on cineangiogram. RESULTS: Four (44.4%) patients showed
      concomitant CAD. The presence of coronary risk factors was not different between
      patients with and without CAD. Contrast media-enhanced tumor vasculature was
      found in five (55.6%) patients. Four (80%) patients had multiple feeding
      arteries. There was the characteristic "sea anemone" appearance of the tumor
      vasculature composed of (1) basal vascular network, (2) vessel stem, (3) backbone
      branches, and (4) dye brushes. These findings were characteristic of cardiac
      myxoma. CONCLUSION: Coronary angiography can detect the concomitant coronary
      disease and the unique vascular appearances of cardiac myxoma. Familiarity with
      the "sea-anemone" angiographic findings may help in the diagnosis of cardiac
      myxoma.

PMID- 16450794
TI  - Preinterventional peak monocyte count and in-stent intimal hyperplasia after
      coronary stent implantation in human coronary arteries.
AB  - BACKGROUND: The mechanism of restenosis after stent implantation principally is
      neointimal hyperplasia. There is evidence that monocytes play a important role in
      in-stent restenosis (ISR) after stent implantation. HYPOTHESIS: This study
      assessed the relationship between preinterventional peak monocyte count and
      neointimal growth after successful stent implantation. METHODS: We performed
      coronary stent implantation in 85 patients (85 de novo lesions). Peripheral blood
      sample was obtained in all patients every 12 h before coronary angiography for
      measurement of peripheral monocytes. All patients received angiographic and
      intravascular ultrasound (IVUS) follow-up at 6 months after stenting. RESULTS:
      The preinterventional circulating monocyte count was significantly higher in the
      ISR group than that in the group without ISR (654 +/- 62/vs. 461 +/- 222/mm3, p <
      0.001) and was significantly higher in the reintervention group than that in the
      no-reintervention group (660 +/- 72/ vs. 470 +/- 216/mm3, p< 0.001). The
      incidence of ISR and repeat intervention associated with preinterventional
      monocyte count was highest among the patients in the highest tertile, who were at
      a 2.64-fold increased risk of ISR and 3.22-fold increased risk of repeat
      intervention compared with the patients in the lowest tertile. A significant
      positive correlation was found between preinterventional peak monocyte count and
      preinterventional plaque and media cross-sectional area and follow-up neointima
      area (r = 0.311, p = 0.007, r = 0.465, p < 0.001, respectively). The neointima
      area associated with preinterventional monocyte count was largest among the
      patients in the highest tertile, that is, 2-fold larger than that of the patients
      in the lowest tertile (p < 0.001) and 1.44-fold larger than that of the patients
      in the middle tertile (p = 0.001). CONCLUSION: Our results suggest that
      circulating preinterventional monocytes play a principal role in the process of
      in-stent neointimal growth after successful stent implantation.

PMID- 16450795
TI  - Assessment of continuous positive airway pressure treatment in obstructive sleep
      apnea syndrome using 24-hour urinary catecholamines.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is related to diurnal
      sympathetic hyperactivity and increased blood pressure, both factors that are
      likely to lead to the development of cardiovascular disease. HYPOTHESIS: The
      study investigated whether 24-h urinary catecholamines would reflect the effect
      of obstructive sleep apnea on autonomic activity. METHODS: Standard
      polysomnography was performed in 17 patients with OSAS (age 53.7 +/- 13.5 years,
      mean +/- standard deviation). The number of apnea/hypopnea episodes per hour of
      sleep (apnea/hypopnea index [AHI]); number of oxygen desaturation episodes per
      hour (desaturation index [DSI]); arousals per hour (arousal index); lowest oxygen
      saturation (lowest SpO2); and percentages of stages 1, 2, 3/4, and rapid eye
      movement sleep (% stage 1, -2, and -3/4, and % REM, respectively) were measured.
      Overnight continuous positive airway pressure (CPAP) titration was performed the
      night after the baseline sleep measurements had been taken. Twenty-four-hour
      urinary adrenaline and noradrenaline were also examined. RESULTS: During the CPAP
      treatment, both 24-h urinary adrenaline and noradrenaline were significantly
      lower compared with natural sleep. Continuous positive airway pressure
      significantly decreased the AHI, DSI, % stage 1, and arousal index and
      significantly increased the lowest SpO2. There were no significant differences in
      % stage 2, % stage 3/4, and % REM between before and during CPAP treatment.
      Multiple analysis of covariance tests revealed that lowest SpO2 was the most
      important factor for increasing 24-h urinary noradrenaline levels (F = 4.75, p =
      0.048). CONCLUSIONS: One night CPAP treatment could improve autonomic
      dysfunction. The assessment of 24-h urinary noradrenaline would provide important
      information for evaluating the effect of CPAP treatment.

PMID- 16450796
TI  - Dobutamine stress echocardiography can predict reversible ventricular dysfunction
      after acute myocardial infarction.
AB  - BACKGROUND: The aim of early treatment of acute myocardial infarction (AMI) is to
      achieve the rapid reperfusion of the culprit artery, which correlates with
      improvement in ventricular function and survival. With the widespread use of
      thrombolytic agents or coronary angioplasty as reperfusion strategies for AMI, it
      is possible to reduce the amount of myocardial necrosis. HYPOTHESIS: The
      assessment of residual viability with dobutamine stress echocardiography (DSE) in
      the infarcted area after AMI is relevant to subsequent management and prognosis.
      METHODS: Thirty-seven patients with AMI (mean age 59 +/- 12, 31 male, 22 with
      anterior AMI, 15 with inferior AMI) admitted to the coronary care unit within 3.8
      +/- 1.8 h of the onset of symptoms were included. Two-dimensional
      echocardiography (2-D echo) study and DSE were performed at a mean of 4.7 +/- 1.8
      days. Follow-up 2-D echo was performed at a mean of 25 +/- 11 days. To assess
      left ventricular regional systolic function, 2-D echo images were obtained at
      rest and during dobutamine-induced stress and were analyzed off-line according to
      the 13-segment model. Improvement in wall motion score (WMS) was defined by a
      decrease of at least two grades in the score. RESULTS: Wall motion score improved
      in 13 of the 37 patients after DSE (rest WMS 20.9 +/- 2.0 vs. D-WMS 17.7 +/- 2.2;
      p<0.001), which correlated with clinical or angiographic signs of reperfusion of
      the culprit vessel in all cases. Follow-up WMS evidenced a significant
      correlation with WMS after DSE (r = 0.91; p < 0.001). Sensitivity, specificity,
      and positive and negative predictive values of DSE in detecting patients whose
      left ventricular function (LVF) improved at 2-D echo follow-up were 72,96,92.8,
      and 82.7%, respectively. CONCLUSIONS: (1) Dobutamine stress echocardiography
      improved WMS in 35% of patients and correlated with signs of patency of the
      culprit vessel; (2) LVF improvement after dobutamine was predictive of late LVF
      recovery; (3) DSE can be a useful and safe tool for detecting reversible
      myocardial dysfunction after AMI.

PMID- 16450797
TI  - Low rates of exercise in patients with metabolic syndrome after an acute coronary
      syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetSyn) has reached epidemic proportions;
      however, regular exercise can prevent its progression to type 2 diabetes.
      HYPOTHESIS: The study was undertaken to determine both the rate and predictors of
      routine exercise 1 year after an acute coronary syndrome (ACS) in patients with
      MetSyn. METHODS: In a registry of 1,199 patients presenting with ACS, those with
      MetSyn were identified using the modified NCEP-ATP III criteria. Baseline and 1
      year exercise patterns were examined in these patients, and the characteristics
      of those who were exercising were then compared with those who were not. A
      multivariable logistic regression analysis was subsequently conducted to identify
      independent predictors of exercise at 1 year. RESULTS: Of 273 patients with
      MetSyn, baseline and 1-year data about patients' exercise patterns were available
      for 170, of whom only 92 (54.2%) were exercising at 1 year. Characteristics that
      differed between those who were and those who were not exercising at 1 year
      included exercise at baseline (40 vs. 16.7%, p<0.001), Caucasian race (92.4 vs.
      79.5%, p = 0.01), and body mass index (BMI) (30.4 +/- 4.3 vs. 32.1 +/- 5.0, p =
      0.02). In a multivariable analysis, significant independent predictors of
      exercise were routine exercise at the time of admission for ACS (odds ratio [OR]
      = 2.6,95% confidence interval [CI] = 1.1-6.4), younger age (OR = 0.67 per 10-year
      increase [95% CI = 0.45-0.99]), and lower BMI (OR = 0.4 per 10-unit increase [95%
      CI = 0.17-0.911). CONCLUSIONS: Almost half of patients with MetSyn did not
      participate in routine exercise 1 year after their admission for ACS. Innovative
      strategies are needed to increase exercise participation in such patients,
      particularly those not exercising at baseline as well as obese and older
      patients.

PMID- 16450798
TI  - Usefulness of low-density lipoprotein particle size measurement in cardiovascular
      disease prevention.
AB  - BACKGROUND: Cardiovascular disease is largely explained by the traditional risk
      factors, but there are several novel risk factors that have been shown to predict
      cardiovascular morbidity. The measurement of low-density lipoprotein particle
      size (LDLPS) is a novel cardiovascular risk factor, yet it is unknown whether
      this measurement provides additional information that may influence the
      subsequent medical treatment of patients. HYPOTHESIS: The measurement of LDLPS
      provides additional information that may influence preventive treatment for
      cardiovascular disease. METHODS: In an observational study of 82 patients
      referred to a tertiary care preventive cardiology clinic, LDLPS was dichotomized
      as either small or large and was determined by either the NMR LipoProfile test,
      the Vertical Auto Profile (VAP) cholesterol test, or gradient gel
      electrophoresis. Lipid profiles were obtained and Framingham risk scores were
      calculated. Patients were stratified by Adult Treatment Panel guidelines as being
      at low, intermediate, or high risk. RESULTS: The study included 56 men and 26
      women with a mean age of 54 +/- 11 years. In the entire cohort of 82 patients,
      only 31 (38%) were at non-high-density lipoprotein (HDL) goal, only 21 (26%) were
      at goals for both non-HDL and HDL, and only 18 (22%) were at goal for non-HDL,
      HDL, and triglycerides. When considering each of the risk factor strata, 19 of 43
      (44%) low-risk patients were at non-HDL goal and 12 of these also had a small
      LDLPS. Only 8 of 18 (44%) intermediate-risk patients were at non-HDL goal and 7
      of these (88%) had small LDLPS. Finally, only four high-risk patients were at non
      HDL goal and three of these (75%) had small LDLPS. CONCLUSIONS: Knowing the LDLPS
      could alter subsequent therapeutic recommendations for most patients who have
      reached target lipid values.

PMID- 16450799
TI  - Sudden cardiac death associated with an extremely rare coronary anomaly of the
      left and right coronary arteries arising exclusively from the posterior
      (noncoronary) sinus of valsalva.
AB  - Congenital anomalies of the coronary arteries are relatively uncommon conditions
      and have been associated with sudden cardiac death (SCD) in children. Although
      anomalous coronary artery distribution is widely reported in the literature, no
      articles to date address the origin of both the right (RCA) and left coronary
      arteries (LCA) from the posterior (noncoronary) sinus of Valsalva. This is a
      report of a 16-year-old black male in good health, who collapsed and was unable
      to be resuscitated after physical exertion while playing basketball. In this
      patient, postmortem evaluation revealed the LCA and RCA originating exclusively
      from the posterior (noncoronary) sinus with acute angle takeoff of the LCA which
      likely lead to ischemia, causing SCD. We discuss the incidence of coronary artery
      anomalies and the proposed mechanisms that led to SCD in these patients.

PMID- 16450800
TI  - Images in cardiology: magnetic resonance imaging of left ventricular lateral wall
      pseudoaneurysm.

PMID- 16450801
TI  - Alfred Wilhelm Volkmann.

PMID- 16450802
TI  - Controversies in the management of intracerebral hemorrhage.

PMID- 16450803
TI  - Primary intracerebral hemorrhage: pathophysiology.
AB  - We here review the pathophysiology of primary intracerebral hemorrhage to compare
      and contrast bleeds due to hypertension and congophilic angiopathy. Hypertension
      is characterized by early proliferation of arteriolar smooth muscle, followed
      later by apoptotic smooth muscle cell death and collagen deposition. Eventually
      excess or deficient collagen deposition can lead respectively to arteriolar
      occlusion, ectasia or both. Collagen has no contractile capability and is
      brittle, unable to withstand breakage due to pulse pressure. Arterioles
      physiologically bring down both blood pressure and pulse pressure, but excessive
      dilatation results in Charcot-Bouchard aneurysms, which are fusiform, not
      saccular structures. The distribution of hypertensive hemorrhage reflects the
      high pulse pressure of arterioles immediately downstream from major end arteries
      with minimal intervening branching. Cerebrovascular amyloidosis is a stagnant
      beta-fibrillosis of arterioles, arising from failure of brain egress of beta
      amyloid, after amyloid precursor protein cleavage within brain parenchyma. The
      lobar distribution of changes reflect an impairment of amyloid removal from brain
      interstitial fluid and Virchow-Robin spaces. Both diseases cause similar brittle
      arterioles with poor contractile capability, likely accounting for early growth
      of hematomas when they rupture. Fibrin globes form in concentric spheres and
      attempt to seal off the site of bleeding. The size of the final sphere of blood
      at cessation of bleeding determines the clinical spectrum, from asymptomatic to
      fatal. Since arteriolar bleeding is slower than arterial bleeding, several hours
      exist where intervention may be useful with recombinant factor VIIa or other
      therapies. We speculate on the importance of pulse pressure in the etiology of
      hemorrhage and resolve the debate over the existence of Charcot-Bouchard
      aneurysms. The high pulse pressure and brisk interstitial fluid pumping in
      Virchow-Robin spaces deep within the brain selectively protects against
      amyloidosis, while leaving these basal arterioles vulnerable to hypertensive
      damage. Hypertensive hemorrhages occur deep within the centrencephalon, while
      amyloid hemorrhages occur in a lobar distribution, where pulse pressure and bulk
      flow are less, away from the major feeding vessels of the brain. The brain
      distributions of hypertensive and of amyloid hemorrhages are thus different and
      complementary.

PMID- 16450804
TI  - Controversies in medical management of intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating form of stroke that is associated
      with a very high mortality rate. Both medical therapies to control blood
      pressure, blood sugar, temperature, and surgical therapies to remove or contain
      clot remain controversial. The decision when to offer medical versus surgical
      treatment is very challenging and uncertain. Novel therapies are currently being
      developed and may be successful in containing the neurological injury associated
      with ICH. This review will highlight the controversies underlying medical
      management of ICH and the current ongoing research in the field.

PMID- 16450805
TI  - Spontaneous supratentorial intracerebral hemorrhage: the role of surgical
      management.
AB  - Spontaneous supratentorial intracerebral hemorrhage is a vexing clinical problem.
      Without established guidelines, clinicians are often forced to make case-by-case
      decisions, based on their own interpretation of relevant studies and experience.
      A number of randomized studies and several meta-analyses have been unable to
      provide a clear indication for surgery for this condition. Data from both
      experimental and clinical studies suggest that early surgical evacuation in some
      circumstances may be beneficial. This may include a subset of patients with
      moderate sized hemorrhages and associated moderate neurological deficits;
      specifically those patients that are likely to survive the primary bleed but with
      significant permanent neurological deficits. Minimal access surgical techniques
      may offer advantages over standard large craniotomies, although a role for
      stereotactic aspirations has not yet been established. The timing of any surgery
      may also be important with theoretical advantages associated with early and
      thorough clot evacuation. Future surgical advances will require techniques or
      adjuvant medical treatment to reduce the occurrence of clot expansion and
      rebleeding, that have been identified as a source of early deteration and post
      operative condition. We review the randomized clinical trials, experimental
      evidence and management options related to surgical treatment of spontaneous
      supratentorial intracerebral hemorrhage.

PMID- 16450806
TI  - Ultra-early hemostatic therapy for primary intracerebral hemorrhage: a review.
AB  - Stroke is a major health problem worldwide, causing high morbidity and mortality.
      Intracerebral hemorrhage (ICH) accounts for 10% of stroke cases in the United
      States and Europe and up to 30% in Asian populations. Intracerebral hemorrhage is
      less treatable than other forms of stroke and causes higher morbidity and
      disability. Data suggest that early hematoma growth is the principal cause of
      early neurological deterioration after ICH. Prospective and retrospective studies
      indicate that early hematoma growth occurs in 18-38% of patients scanned within
      three hours of ICH onset, and that hematoma volume is an important predictor of
      30-day mortality. Recombinant activated factor VII (rFVIIa, NovoSeven), a
      powerful initiator of hemostasis, is approved for the treatment of bleeding in
      patients with hemophilia and inhibitors, and can also promote hemostasis in
      patients with normal coagulation. A Phase-IIB randomized, double-blind, placebo
      controlled, dose-ranging trial has been conducted in 399 patients with ICH to
      investigate the potential of rFVIIa as an ultra-early hemostatic therapy. A
      reduction in hematoma growth in non-coagulopathic ICH patients was evident with
      reduced mortality and improved clinical outcome at three months. The significance
      of these findings for neurocritical care is discussed.

PMID- 16450808
TI  - Prevention of sudden cardiac death.
AB  - It is often unclear why some patients suffer sudden cardiac death (SCD), or even
      what risk factors correlate best with the syndrome. This review describes current
      thinking on the prevention of SCD. Most studies have focused on the prevention of
      potentially fatal ventricular arrhythmias in patients post myocardial infarction
      (MI). While pharmacotherapy has a role in the prevention of SCD in patients post
      MI, the interpretation of drug trials can be problematic. This is because not all
      patients participating in such trials received optimized medical therapy by
      today's standards. As a result, trial outcomes for new therapies may not reflect
      their true efficacy when they are added to a background of best medical care. The
      two principal prophylactic modalities for SCD studied to date are antiarrhythmic
      drug therapy and use of an implantable cardioverter defibrillator (ICD). At the
      present time, antiarrhythmic drugs, such as the class III agent amiodarone, seem
      to display relatively limited efficacy for the primary prevention of sudden death
      in most patients post MI. Most clinical trials have found that ICD therapy has a
      significant mortality benefit in patients at high risk for ventricular
      arrhythmias. This has been demonstrated in primary prevention trials, and in
      secondary prevention trials such as Antiarrhythmics Versus Implantable
      Defibrillators (AVID), which studied patients who survived a near-fatal
      ventricular arrhythmia. Based on an analysis of secondary prevention trials, the
      single patient characteristic that best predicted an advantage of ICD therapy
      over antiarrhythmic drug therapy was a left ventricular (LV) ejection fraction <
      or = 35%. Cardiac resynchronization therapy has been established as having a
      mortality benefit in patients with dyssynchronous LV contraction associated with
      dilated cardiomyopathy.

PMID- 16450807
TI  - Epidemiology and stratification of risk for sudden cardiac death.
AB  - Sudden cardiac death (SCD) is a major cause of mortality in the United States.
      Approximately 65% of cases of SCD occur in patients with underlying acute or
      chronic ischemic heart disease. The incidence of SCD increases 2- to 4-fold in
      the presence of coronary disease and 6- to 10-fold in the presence of structural
      heart disease. Ventricular fibrillation (VF) precipitated by ventricular
      tachycardia (VT) is a common mechanism of cardiac arrest leading to SCD. Triggers
      for SCD include electrolyte disturbances, heart failure, and transient ischemia.
      Although a large percentage of patients with out-of-hospital SCD do not survive,
      successful resuscitation to hospitalization has improved in recent years. One of
      the challenges for preventing SCD lies in identifying individuals at highest risk
      for SCD within a lower-risk population. The progression from conventional risk
      factors of coronary artery disease to arrhythmogenesis and SCD can be represented
      as a cascade of changes associated with levels of increasing risk. At the first
      level is atherogenesis, followed by changes in atherosclerotic plaque anatomy,
      which may be mediated by inflammatory processes. Disruption of active plaque
      formed during a transitional state initiates the thrombotic cascade and acute
      occlusion, after which acute changes in myocardial electrophysiology become the
      immediate trigger for arrhythmogenesis and SCD. Each level of the cascade offers
      different opportunities for risk prediction. Among the classes of risk predictors
      are clinical markers, such as ECG measures and ejection fraction. Transient risk
      markers, such as inflammatory markers, are potentially useful for identifying
      triggers for SCD. In the future, genetic profiling is expected to allow better
      assessment of individual risks for SCD.

PMID- 16450809
TI  - Reducing the risks of sudden death and heart failure post myocardial infarction:
      utility of optimized pharmacotherapy.
AB  - Current guidelines define the standard of care for patients after myocardial
      infarction (MI), with particular focus on patients with significant ventricular
      dysfunction. Inherent in these recommendations are assumptions about the relative
      risks and benefits, as well as the costs, of the available options. This review
      will consider strategies to prevent sudden death and heart failure post-MI by
      utilization of pharmacologic therapies--angiotensin-converting enzyme (ACE)
      inhibitors, angiotensin receptor blockers (ARB), aldosterone antagonists,
      statins, and beta-blockers--in parallel with the approaches reviewed elsewhere in
      this supplement. A patient-centric approach necessitates that drugs in each class
      be compared for efficacy within this patient population. Clinical trials have
      demonstrated the efficacy of several drugs, such as ACE inhibitors, beta
      blockers, and aldosterone antagonists, in patients post-MI, yet these benefits do
      not seem to be reflected in the epidemiologic data. This may reflect
      underutilization of these therapies or, alternatively, support the notion that
      efficacy in clinical trials does not assure effectiveness in clinical practice.
      The latter point is a subject of ongoing investigation, while the former is being
      addressed through quality-of-care initiatives. In clinical practice,
      aggressiveness is key, starting with patient education. If patients understand
      their risks better, compliance and adoption of a more ideal lifestyle seem more
      likely. However, even with educational programs, human nature teaches us that
      marked change in behavior is difficult and therefore, to minimize risks,
      particularly of sudden death and heart failure post infarction, an optimized
      pharmacologic regimen serves as a powerful tool.

PMID- 16450811
TI  - Coronary interventions and their impact on post myocardial infarction survival.
AB  - Rapid reestablishment of infarct vessel patency and microvascular flow provides
      the best opportunity for minimizing mortality in the patient post myocardial
      infarction (MI). Early infarct artery patency can be restored by thrombolysis,
      primary angioplasty, or facilitated percutaneous coronary intervention (PCI). In
      comparative studies, primary angioplasty offers a greater mortality benefit than
      thrombolysis in patients with acute MI. Short-term rates of mortality and stroke
      were significantly lower in patients receiving primary angioplasty compared with
      thrombolysis, as was the risk of nonfatal reinfarction. The timing of reperfusion
      therapy after symptom onset affects outcomes. Patients presenting >3 h after
      symptom onset are likely to benefit more from PCI than from thrombolysis.
      Nevertheless, PCI should be performed as soon as possible for optimal results. If
      PCI is to be delayed, then immediate thrombolysis is likely to be as effective as
      PCI. Registry data indicate that reperfusion for acute MI is currently underused,
      with different techniques frequently misapplied. Outcomes tend to be better at
      centers that perform a high volume of reperfusion procedures, partly due to
      shorter treatment delays. Facilitated PCI combines fibrinolytic therapy with
      angioplasty. It is designed to promote very early patency in those who respond to
      drug therapy, with very high final patency rates assured by angioplasty. Clinical
      trials have generally found facilitated PCI to be more efficacious than
      thrombolysis alone. Rescue PCI in cases of failed fibrinolysis is associated with
      a modest mortality benefit compared with conservative treatment. Myocardial
      injury following reperfusion after ischemia can limit the benefits of PCI and
      fibrinolysis; however, strategies for minimizing reperfusion injury have not yet
      shown clinical efficacy.

PMID- 16450810
TI  - Practical algorithms for pharmacologic management of the post myocardial
      infarction patient.
AB  - The pharmacologic management of the patient post myocardial infarction (MI) aims
      to achieve several goals. Chief among these is to prevent subsequent events,
      which include death, reinfarction, and rehospitalization. Secondary goals include
      preventing arrhythmias, minimizing left ventricular (LV) remodeling, and
      preventing progression to heart failure. This review describes practical
      algorithms for use in the pharmacologic management of the patient post MI based
      on American Heart Association/American College of Cardiology guidelines. The
      intensity of drug treatment is determined guided by the degree of LV dysfunction
      and the presence or absence of ischemia and arrhythmic risk markers. All patients
      post MI require an angiotensin-converting enzyme (ACE) inhibitor and antiplatelet
      therapy, usually with aspirin. In individuals who cannot tolerate an ACE
      inhibitor, an angiotensin receptor blocker (ARB) is an adequate substitute.
      Numerous studies document the efficacy of ACE inhibitors, which decrease
      mortality and the risk of heart failure and stroke. Aldosterone blockade is
      recommended long-term for patients post MI with an LV ejection fraction < or =
      40% and either symptomatic heart failure or diabetes. Use of a beta blocker is an
      important addition to most post-MI drug regimens. Beta blockers decrease
      mortality and are especially effective in patients with impaired LV function.
      Among the beta blockers, carvedilol, which also has alpha-adrenergic receptor
      blocking activity, was found to decrease mortality significantly in patients with
      low ejection fractions and heart failure. Another drug therapy of value in post
      MI treatment is use of calcium-channel blockers. These are restricted to patients
      with conserved LV function in whom congestion is absent and in whom beta blockers
      are contraindicated. Current guidelines also recommend that patients post MI with
      elevated cholesterol levels should be prescribed lipid therapy with a statin at
      hospital discharge.

PMID- 16450812
TI  - New insights into cardiac resynchronization therapy.
AB  - Ventricular dyssynchrony plays a central role in the expression and progression
      of heart failure (HF). An independent risk factor for cardiac mortality,
      ventricular dyssynchrony is characterized by delay in left ventricular (LV)
      lateral wall contraction. This leads to decreased pumping efficiency, with
      resulting fluid retention and impaired exercise tolerance. Cardiac
      resynchronization therapy (CRT) attempts to improve cardiac efficiency by
      restoring the normal mechanical relationship between right and left ventricular
      contraction. Cardiac output increases with resynchronization, while ventricular
      filling pressure decreases without increasing cardiac oxygen consumption. Cardiac
      resynchronization therapy can also reverse LV dysfunction and reduce mitral
      regurgitation in patients with HF. Since 1999, the efficacy of implantable CRT
      devices has been evaluated in clinical trials enrolling more than 4,000 patients
      with heart disease. In the CARE-HF trial, CRT reduced the risk of death by 36%
      relative to standard pharmacologic therapy. Combining CRT with a defibrillator
      might produce an added benefit. In the COMPANION trial, all-cause mortality in
      patients randomized to a CRT-defibrillator combination was less than in patients
      receiving CRT therapy alone. Cardiac resynchronization therapy has also been
      found to decrease morbidity and improve functional status and quality of life. At
      the present time, the indications for CRT are limited and include symptomatic HF
      despite optimal medical therapy, prolonged QRS interval, and LVEF < or = 35%.
      However, indications for CRT are still evolving and may be expanded as further
      studies identify those most likely to benefit.

PMID- 16450813
TI  - Post myocardial infarction, left ventricular dysfunction, and the expanding role
      of cardiac implantable electrical devices.
AB  - In patients post myocardial infarction (MI) at risk for fatal ventricular
      arrhythmias, cardiac implantable devices offer a means of preventive therapy that
      complements optimal pharmacologic therapy. In patients with depressed ejection
      fractions, prophylactic implantable cardioverter defibrillators (ICDs)
      significantly improve survival. The efficacy of ICDs in the primary prevention of
      sudden cardiac death in patients post MI has been examined in a number of major
      primary prevention trials. These trials demonstrated as much benefit as some
      secondary prevention trials, which were conducted in high-risk patients who
      already had a spontaneous sustained ventricular tachyarrhythmia. In patients who
      are candidates for an ICD, best medical therapy for left ventricular dysfunction
      should be in place for some time before implanting. This waiting period could
      mean avoiding the implantation of a device in a patient who would heal
      sufficiently with pharmacologic therapy alone. In New York Heart Association
      (NYHA) class III and IV, patients with heart failure, and QRS intervals > or =
      120 ms, cardiac resynchronization therapy (CRT) in combination with a
      defibrillator is a valuable addition to optimal pharmacologic therapy. Recent
      studies have demonstrated improved survival with CRT as well as improved quality
      of life. The high cost of cardiac implantable devices has led the Centers for
      Medicare and Medicaid Services to impose strict indications for use. However, it
      is likely that indications will be broadened for ICDs to include selected
      patients with left ventricular ejection fraction up to 40%, compared with the
      current indication of < or = 30%. Implanted devices must be followed up
      appropriately, with periodic interrogation and program adjustment to reduce the
      risk for pacing-induced desynchronization and to optimize hemodynamic benefit.

PMID- 16450815
TI  - Screening for prostate cancer in military populations.
AB  - With the widespread use of the prostate-specific antigen (PSA) test, smaller
      cancers are being detected among younger men and 5-year, cancer-specific,
      survival rates are on the rise. Although this lead-time effect may not translate
      into long-term improvement, these changes are a necessary prerequisite to
      effective screening. For high-risk patients, i.e., men with a family history of
      the disease and African American men, a strategy consisting of annual PSA blood
      testing and digital rectal examination for men > or = 40 years of age appears
      prudent. Many low/average-risk men of age 40 to 49 also request testing, and it
      is reasonable to offer testing and risk assessment to them. The exact screening
      threshold for total PSA levels for these men is not known, but 95% have PSA
      levels of < or = 1.5 to 2.5 ng/mL. PSA velocity (< 20% per year), percentage of
      free PSA (> 18-25%), and complexed PSA levels may be used to help determine risk.
      More study of young men is needed.

PMID- 16450814
TI  - Real-world algorithms for the optimal use of drugs and devices in the patient
      post myocardial infarction and the future of post myocardial infarction
      management.
AB  - Patients with left ventricular dysfunction (LVD) are at increased risk for dying
      suddenly of cardiac causes. The most common causes of LVD are coronary artery
      disease (CAD) and myocardial infarction (MI). Aggressive intervention following
      MI is essential for minimizing the myocardial damage that leads to LVD and the
      subsequent risk for heart failure and sudden cardiac death. This article
      describes practical algorithms for managing the patient post MI to minimize such
      risks. The degree of LVD is a key factor for determining clinical management
      strategies in the patient post MI. Risk factor reduction and selective
      neurohormonal blockade, especially with angiotensin-converting enzyme inhibitors,
      are usually recommended in the presence or absence of LVD, along with early use
      of a beta blocker. In patients with LVD, more aggressive intervention includes
      extended use of a beta blocker. In cases of LVD progressed to heart failure, the
      mixed beta and alpha blocker carvedilol has improved outcomes significantly. In
      clinical trials, carvedilol has been demonstrated to have antiarrhythmic
      activity, a property that offers protection against sudden arrhythmic death in
      high-risk patients with LVD. Addition of an aldosterone antagonist is also
      advised in patients with heart failure. In selected patients with reduced
      ejection fractions, use of surgical/catheter treatment and device therapy offers
      further benefits.

PMID- 16450816
TI  - Medical errors--is total quality management for the battlefield desirable?
AB  - There has recently been a great deal of discussion in both the lay press as well
      as the medical press regarding the incidence of errors that occur during medical
      practice. There have been many discussions of how quality control measures from
      industry can be applied to the health care system. Indeed both civilian and
      "brick and mortar" military medical treatment facilities are adapting these
      techniques. It is important that we understand the principles behind Total
      Quality Management (TQM) as well as its techniques and limitations. TQM is based
      on limiting deviation from an accepted standard of practice. These principles may
      be as applicable to our military health care facilities in a field environment as
      they are to our fixed facilities, although the standards used for measurement may
      have to be modified to adapt to different constraints of environment and
      resources. TQM techniques can nonetheless be applied in virtually any facility to
      ensure the best possible care and outcomes for our soldiers.

PMID- 16450817
TI  - Burn injury care for Special Forces and far-forward deployed troops.
AB  - Special Forces are at risk of serious burn injury. We have suggested standard
      operating procedures for burn injury management in a constrained environment,
      with novel uses of operational kit components for trauma care. In addition, we
      propose instruction in basic skills of escharotomy for forward troops.

PMID- 16450818
TI  - Use of a hemorrhage simulator to train military medics.
AB  - BACKGROUND: The leading cause of preventable battlefield death is extremity
      hemorrhage. This study examines how current first aid training for the management
      of severe extremity hemorrhage can be improved by using a patient simulator.
      METHODS: This was a prospective trial involving two cohorts of U.S. Army combat
      medic trainees. The control group received the standard first aid training for
      bleeding, including lectures and practical exercises. The study group received
      the same lectures but was exposed to a hemorrhage simulator during the practical
      exercises. Both groups were then evaluated during a field exercise 7 weeks later.
      RESULTS: The study group showed a statistically significant improvement in the
      time it took to stop severe extremity hemorrhage in a simulated patient.
      CONCLUSIONS: Simple innovations in training may play a significant role in
      preparing medics (and combatants) to care for injuries they will encounter on the
      battlefield.

PMID- 16450819
TI  - Narrowing of lumbar spinal canal predicts chronic low back pain more accurately
      than intervertebral disc degeneration: a magnetic resonance imaging study in
      young Finnish male conscripts.
AB  - The objective of this magnetic resonance imaging study was to evaluate the role
      of degenerative changes, developmental spinal stenosis, and compression of spinal
      nerve roots in chronic low back (CLBP) and radicular pain in Finnish conscripts.
      The degree of degeneration, protrusion, and herniation of the intervertebral
      discs and stenosis of the nerve root canals was evaluated, and the midsagittal
      diameter and cross-sectional area of the lumbar vertebrae canal were measured in
      108 conscripts with CLBP and 90 asymptomatic controls. The midsagittal diameters
      at L1-L4 levels were significantly smaller in the patients with CLBP than in the
      controls. Moreover, degeneration of the L4/5 disc and protrusion or herniation of
      the L5/S1 disc and stenosis of the nerve root canals at level L5/S1 were more
      frequent among the CLBP patients. Multifactorial analysis of the magnetic
      resonance imaging findings provided a total explanatory rate of only 33%.
      Narrowing of the vertebral canal in the anteroposterior direction was more likely
      to produce CLBP and radiating pain than intervertebral disc degeneration or
      narrowing of the intervertebral nerve root canals.

PMID- 16450820
TI  - Evaluation of intravenous cannula and administration set fixation methods.
AB  - Intravenous cannula and administration set fixation is crucial for fluid
      resuscitation and intravenous administration of medications. Because conventional
      hospital fixations are insufficient for the military field scenario, two
      consecutive, prospective, randomized, clinical trials were performed in the
      Israel Defense Forces Medical School, to determine the most effective fixation
      method in the military arena. Gauze bandage, adhesive bandage, Coban wrap, and
      plastic wrap fixation methods were tested for field conditions and intravenous
      fluid flow. The results showed that plastic wrap is the fastest fixation method,
      withstands field conditions with minimal negative effects on the intravenous
      fluid flow, and is the most cost-effective.

PMID- 16450821
TI  - Health effects in Army Gulf War veterans possibly exposed to chemical munitions
      destruction at Khamisiyah, Iraq: Part I. Morbidity associated with potential
      exposure.
AB  - In March 1991, U.S. troops detonated the Khamisiyah, Iraq, ammunition depot,
      possibly releasing two chemical warfare agents, sarin and cyclosarin. The long
      term health effects associated with possible exposure to these chemical warfare
      agents are unknown. This study was undertaken to investigate whether possible
      exposure was associated with morbidity among Army Gulf War veterans using
      morbidity data for 5,555 Army veterans who were deployed to the Gulf region.
      Responses to 86 self-assessed health measures, as reported in the 1995 Department
      of Veterans Affairs National Health Survey of Gulf War Era Veterans, were
      evaluated. We found little association between potential exposure and health,
      after adjustment for demographic variables, and conclude that potential exposure
      to sarin or cyclosarin at Khamisiyah does not seem to have adversely affected
      self-perceived health status, as evidenced by a wide range of health measures.

PMID- 16450822
TI  - Health effects in Army Gulf War veterans possibly exposed to chemical munitions
      destruction at Khamisiyah, Iraq: Part II. Morbidity associated with notification
      of potential exposure.
AB  - The purpose of this study was to examine the association of notification of
      potential exposure to chemical warfare agents in the 1991 Gulf War with
      subsequent self-reported morbidity. The study sample included 1,056 deployed Army
      Gulf War veterans who responded to the 1995 National Health Survey of Gulf War
      Era Veterans and who were resurveyed in 2000. One-half of the subjects had been
      notified of potential exposure to chemical warfare agents and one-half had not.
      Comparing notified and non-notified subjects, there were no statistically
      significant differences with respect to bed days, activity limitations, clinic
      visits, or hospital visits. Among 71 self-reported medical conditions and
      symptoms, there were 5 statistically significant differences, 4 of which were for
      lower rates of illness among notified subjects. Our findings contradict the
      prevailing notion that perceived exposure to chemical warfare agents should be
      considered an important cause of morbidity among Gulf War veterans.

PMID- 16450824
TI  - The psychometric properties of the Stages of Change Readiness and Treatment
      Eagerness Scale (SOCRATES) in a clinical sample of active duty military service
      members.
AB  - The increasing prominence of the construct of readiness to change in the field of
      substance abuse treatment has led to the development of instruments designed to
      assess the construct. We examined the psychometric properties of one such
      instrument, the Stages of Change Readiness and Treatment Eagerness Scale
      (SOCRATES), in a sample of treatment-seeking, active duty, U.S. military service
      members diagnosed with alcohol and/or drug dependence. A principal components
      analysis of the items was consistent with the tridimensional structure of the
      SOCRATES found among treatment-seeking civilians but resulted in a 14-item scale,
      as opposed to the 19-item version found for civilians. Normative data, in the
      form of means and decile rankings for the SOCRATES subscales, for substance
      dependent military patients are provided to complement those available for
      civilian patients. Future research should examine the concurrent and predictive
      validity of the scale.

PMID- 16450823
TI  - Organization and management of care for military veterans with human
      immunodeficiency virus/acquired immunodeficiency syndrome in Department of
      Veterans Affairs Medical Centers.
AB  - OBJECTIVE: As the largest provider of human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome health care services, the Department of Veterans
      Affairs (VA) has launched a national quality improvement program. As a first
      step, an assessment of how care for veterans with HIV/acquired immunodeficiency
      syndrome was organized was conducted. METHODS: Structured surveys were
      administered to senior HIV clinicians in 118 VA facilities, about local
      approaches to structuring, staffing, and delivering HIV health services. RESULTS:
      HIV care was chiefly delivered in special VA-based HIV clinics. HIV-related
      services were widely available on site, with non-VA referrals being more commonly
      needed to meet long-term care needs. Urban VA facilities had greater HIV
      caseloads, were more likely to have separate HIV clinics, and had greater access
      to HIV expertise, whereas rural practices focused on primary care-based models
      and tended to rely on off-site VA HIV experts. CONCLUSIONS: Understanding the
      organization and management of VA-based HIV services will help design systematic
      quality improvement efforts and meet the treatment needs of HIV-infected
      veterans.

PMID- 16450825
TI  - The potential of risk adjustment for the Military Health System TRICARE Program.
AB  - Using industry leading methods and software products, this article explores the
      potential for health risk adjustment in the Department of Defense (DoD) Military
      Health System. From an epidemiologic perspective, the study assesses whether DoD
      populations enrolled to and served by different provider groups exhibit
      sufficient variation in risk to justify changes in resource allocation, such as
      staffing, services, and facility modification. In addition, the study
      investigates whether systematic differences in risk exist between TRICARE
      enrollees and commercially insured enrollees. Given the interest of the DoD in
      managed care, risk prediction tools are shown to project future risk for
      individuals with sufficient accuracy to justify development of disease management
      programs for patients with chronic conditions. Analyses demonstrate that Military
      Health System data support industry requirements to perform risk grouping among a
      random sample of 200,000 enrollees selected from 495,941 eligible enrollees.

PMID- 16450826
TI  - Impetigo in soldiers after hand-to-hand combat training.
AB  - Bacterial skin infections are very common and trigger destruction of the skin
      integrity. Impetigo is a consequence of group A beta-hemolytic streptococcus or
      Staphylococcus aureus infection. The clinical presentation in general is very
      typical and empiric treatment is usually successful. In cases of close contacts
      such as between classmates, athletes, or soldiers, the prompt recognition and
      appropriate treatment of the infection may stop an epidemic. We report a group of
      six soldiers who shared the same military equipment (physical shields) during
      hand-to-hand combat training. All of the soldiers had skin lesions and two of
      them suffered from systemic symptoms. Group A beta-hemolytic streptococcus and S.
      aureus were cultured from the impetiginous lesions. All patients recovered after
      systemic and/or local antibiotic treatments. These cases emphasize the need for
      the maintenance of proper hygiene throughout the training program to prevent
      spread of the disease and the importance of rapid diagnosis by bacteriological
      identification.

PMID- 16450827
TI  - Novel nutritional immune formula maintains host defense mechanisms.
AB  - Military combat and training stress induce immune changes that increase the risk
      of infection and ultimately influence soldiers' performance and readiness.
      Strenuous military training/assessment provides a uniform stress and the
      opportunity to evaluate nutritional strategies to minimize stress-induced immune
      changes that predispose soldiers to infection. Immunological changes and effects
      of a novel nutritional immune formula (NNIF) were examined prospectively in a
      double-blind, controlled study of 200 soldiers attending Special Forces
      Assessment and Selection School. Immune function was measured by skin delayed
      type hypersensitivity, lymphocyte phenotyping, mitogenic proliferative responses,
      and granulocyte function. Approximately 50% of soldiers completed the study
      (control, n = 57; NNIF, n = 50). Several stress-induced lymphocyte changes were
      observed (decreased mitogen-induced proliferation, T and total lymphocytes, and
      interferon-gamma-producing lymphocytes and increased percentage of neutrophils).
      NNIF modified several changes, including delayed-type hypersensitivity responses
      (NNIF, 78%; control, 59%; p < 0.05), increased proportions of helper T cells,
      activation of B cells, enhanced neutrophil phagocytosis, and attenuation of
      declines in certain functional subpopulations (i.e., cytotoxic/ suppressor
      lymphocytes). Soldiers who consumed NNIF experienced less stress-induced immune
      impairment, thereby lowering the risk of infection.

PMID- 16450828
TI  - Histopathological evaluation of five unusual gingival enlargement cases.
AB  - Gingival fibromatosis represents the fibrous hyperplasia of the gingival tissue.
      Clinical examination reveals enlargement of buccal and palatal gingival tissue.
      Many forms of gingival fibromatosis are of unknown etiology and termed as
      idiopathic gingival fibromatosis. However, several authors use various terms such
      as gingivomatosis and elephantiasis to describe these lesions. Our aim in this
      case report is to present five patients (one female, four males) with unusual
      clinical forms of gingival hyperplasia and to discuss the histopathological and
      clinical features in comparison to similar enlargements. Clinical examinations
      did not reveal increased periodontal pocket depths, besides plaque and gingival
      index scores were found to be in normal range. All of the patients were
      systemically healthy and were not subject to medications, which could lead to
      gingival hyperplasia. Additionally, clinical appearance of the lesions did not
      show any signs of trauma. Excisional biopsies were performed in all cases. The
      pathological examinations of the specimens demonstrated fibroconnective tissue
      characteristics, which were in accordance with the clinical appearance of all
      patients. Lesions healed successfully without sequelae or infection, and no
      recurrence was observed after 1-year follow-up.

PMID- 16450829
TI  - Comprehensive head and neck trauma screening: the USS Cole experience.
AB  - A prospective study was designed to determine the incidence of occult head and
      neck injuries after initial triage of patients following the USS Cole terrorist
      bombing. All 39 patients evacuated to Landstuhl Regional Medical Center underwent
      comprehensive head and neck examinations, regardless of known diagnoses at the
      time of arrival. Appropriate interventions were performed, and detailed summaries
      were added to the patients' records. Initial triage listed nine of 39 patients as
      having sustained head and neck injuries. After screening by an otolaryngology
      team, 23 of 39 patients were identified as having head and neck injuries
      requiring further care. The majority of head and neck injuries were not initially
      reported to the head and neck trauma service. Our conclusion is that occult head
      and neck injuries are common after blast injuries. Early identification and
      intervention by a subspecialty head and neck trauma team can aid in achieving
      optimal outcomes after blast injury.

PMID- 16450830
TI  - Malaria on a military peacekeeping operation: a case study with no case.

PMID- 16450831
TI  - The rare and serious total open luxation of the talus.

PMID- 16450832
TI  - Resolutions.

PMID- 16450833
TI  - Genetic diversity among Lactococcus sp. and Leuconostoc sp. strains using PCR
      RFLP of insertion sequences ISS1-type, IS904, and IS982.
AB  - PCR-RFLP analysis of commonly occurring insertion sequences ISS1-type, IS904 and
      IS982 in Lactococcus sp. and Leuconostoc sp. was used for the genetic
      differentiation of 17 strains of lactic acid bacteria. ISS1-type and IS982 were
      found in all analysed strains while IS904 was present exclusively in strains
      belonging to Lactococcus sp. Amplification of ISS1-type IS sequences resulted in
      formation of about 820 bp long amplicons, except of strains Lactococcus lactis
      ssp. lactis E and Leuconostoc lactis R where extra DNA bands about 370 bp long
      were observed. Similarly for strains of Leuconostoc lactis M and N, additional
      DNA bands about 280 bp long were present. TaqI digestion of ISS1-type amplicons
      revealed that all analysed sequences belonged to the restriction type (ii) or
      (iii) for which major restriction products were 543 and 147 bp long.
      Amplification of IS904 from all strains of Lactococcus sp. generated amplicons
      about 1260 bp long. In three strains of Leuconostoc sp. M, N and R, shorter
      amplicons about 880 bp were observed whereas strains O and P did not contained
      IS904. Amplification of IS982 resulted in formation of amplicons about 1000 bp
      long and no extra bands were observed for all tested strains. TaqI digestion of
      amplification products showed that for strains C, I and F, G, H, belonging to
      Lactococcus sp. smaller DNA bands were visible suggesting that they contain two
      different types of IS982.

PMID- 16450834
TI  - Lysostaphin as a potential therapeutic agent for staphylococcal biofilm
      eradication.
AB  - The aim was to study the activity of lysostaphin in monotherapy or in combination
      with oxacillin, towards biofilms built by clinical and reference S. aureus and S.
      epidermidis strains in the wells of microplate, in the chambers of a LabTekII
      chamber slide or on the polyethylene catheter. MICs of oxacillin and lysostaphin
      for planktonic bacteria were determined according to the standards of NCCLS. BIC
      (Biofilm Inhibitory Concentration) was estimated by the MTT assay. The integrity
      of biofilm treated with antimicrobials was also examined: by staining with FITC
      and laser scanning fluorescence confocal microscopy and visually by TTC reduction
      assay. Despite the fact that susceptibility of planktonic cultures of 25
      staphylococcal strains to lysostaphin action was various, we have demonstrated
      the effectiveness of lysostaphin in the treatment of biofilm, built not only on
      the flat surface of the microplates but also on catheter's surface. The
      synergistic effect of subBIC lysostaphin+oxacillin was observed for MSSA and MRSA
      biofilms but not for 1474/01 hVISA strain. Also BICOXA for S. epidermidis RP12
      and A4c strains, but not for 6756/99 MRSE biofilms was reduced when lysostaphin
      was simultaneously used.

PMID- 16450836
TI  - The prognostic and diagnostic markers of invasive candidiasis in patients during
      chemotherapy.
AB  - The aim of the work was the early detection of Candida spp. in clinical samples
      of patients with carcinoma ovariorum undergoing chemotherapy by comparing three
      indicators of candidiasis: presence of mannan and yeast DNA in the bloodstream
      and colonization of mucosal membranes by Candida species as a prognostic marker
      of deep candidiasis. Thirty-one women with carcinoma ovariorum, during
      chemotherapy without symptoms of deep fungal infections, were examined twice over
      a six-day period. C. albicans was the dominant organism isolated from mucosal
      membranes. Two serum samples were positive for mannan on the first day of
      examination. All these patients were previously colonized by Candida spp. on
      mucous membranes. Four patients were positive on the last day of examination.
      Three of these patients were colonized by Candida spp. C. albicans infection was
      detected early in 4 out of 12 clinical samples by a combination of PCR and mannan
      detecting methods. Colonization increases the risk of deep candidiasis. PCR and
      antigen detection are fast and reliable methods for early detection of Candida in
      bloodstream. For patients at risk, the clinical samples must be tested by at
      least two independent methods.

PMID- 16450835
TI  - GyrA mutations in ciprofloxacin-resistant clinical isolates of Pseudomonas
      aeruginosa in a Silesian Hospital in Poland.
AB  - Among 73 clinical isolates of Pseudomonas aeruginosa 48 strains were
      ciprofloxacine (CIP) susceptible and 25 CIP resistant (Minimal inhibitory
      concentration--MIC>32 microg/ml - 14 strains) or of intermediate susceptibility
      to CIP (MIC > or = 1,5 - 32 microg/ml - 11 isolates). Mutations in the quinolone
      resistance-determining region (QRDR) of gyrA gene were searched in groups of CIP
      resistant and of intermediate susceptibility to CIP isolates. Two methods:
      restriction fragment length polymorphism (RFLP) analysis and DNA sequencing
      analysis allowed to detect three different mutations. The nucleotide
      substitutions observed led to the following amino acid replacements: Thr-83 -->
      Ile, Asp-87 --> Asn, Asp-87 --> Gly. One mutated strain among the group of
      mutants analyzed showed double mutation (Thr-83 --> Ile, Asp-87 --> Gly) and
      additional silent mutation (Val-103 --> Val); whilst the rest of the isolates
      showed different single missense mutations. The most frequently detected mutation
      in the gyrA gene (16 out of 25 mutants) was the Thr-83 --> Ile substitution.

PMID- 16450837
TI  - Seroepidemiological studies of Chlamydia pneumoniae infections in 1-36 months old
      children with respiratory tract infections and other diseases in Poland.
AB  - Presence of specific IgM, IgG and IgA antibodies against Chlamydia pneumoniae was
      evaluated in children aged 1 week to 36 months to investigate the role of C.
      pneumoniae in respiratory infections and other diseases. Serum samples were
      obtained from 150 hospitalized children, including 123 children presenting the
      clinical symptoms of various respiratory tract infections, two children with
      acute diarrhoea, two children with meningitis, 14 children with urinary tract
      infection, and 9 children with non-infectious diseases. Levels of specific C.
      pneumoniae IgM, IgG and IgA serum antibodies were measured by enzyme-linked
      immunoassay (ELISA). C. pneumoniae IgM antibodies were detected in 16 (13.0 %) of
      123 children with respiratory tract infections. Specific IgG antibodies were
      found in sera of 11 children under 12 months old. Among 27 children without
      symptoms of a respiratory tract disease, specific C. pneumoniae IgM were found in
      two (7.4%) children, including one child with meningitis and another child with
      urinary tract infection. Specific IgA antibodies were not found in any tested
      child. All cases of C. pneumoniae infections were identified within two calendar
      years out of eight that were analyzed, i.e. in 1997 and 2000. The incidence of C.
      pneumoniae infections varied seasonally, with most children infected in autumn.
      C. pneumoniae IgM antibodies were detected more often in girls (17.9%) then in
      boys (7.2%). C. pneumoniae infections occur among small children in central
      Poland. The results of this study indicate that C. pneumoniae may play a role in
      the etiology of respiratory tract infections in infants and young children.

PMID- 16450838
TI  - Occurrence of serum class G immunoglobulins interacting with specific antigens of
      Helicobacter pylori in patients with unstable coronary artery disease and in
      symptomless individuals.
AB  - An impact of Helicobacter pylori on the process of atherogenesis may be related
      to the intensity of humoral response against selected specific antigens of this
      bacteria. We performed serological studies in which the recognition of 7 selected
      antigens was possible. The investigated group consisted of 56 patients
      hospitalized due to unstable angina pectoris. The control group consisted of 29
      symptomless volunteers. The levels of class G serum immunoglobulins interacting
      with glycine extract (GE) of H. pylori antigens were assessed by ELISA test in
      both groups. The same sera were tested by the Milenia blot H. pylori IgG system.
      In this assessment the presence of IgG antibodies interacting with antigens of
      molecular weight of 120, 87, 64, 35, 30, 26, and 20 kDa was estimated separately
      for every listed antigen. The results revealed significant differences between
      investigated groups in the prevalence of anti-GE IgG (unstable angina - 100% vs.
      controls - 60%) and in the level of such antibodies expressed as total optical
      density units--OD450 (6.1 +/- 3.0 vs. 3.4 +/- 3.0 respectively, p<0.05). However,
      anti-GE IgG detected in the sera of patients as well as controls reacted with
      similar frequency with selected H. pylori antigens: highly specific (120, 87, 64,
      30 kDa) and specific (35, 26, and 20 kDa). We conclude, that although H. pylori
      infection is so common and mainly associated with gastroduodenal symptoms, it is
      also recognized by serological methods with high prevalence in patients with
      coronary artery disease, and less frequently in symptomless individuals. The
      humoral response against H. pylori in class G immunoglobulins in patients with
      unstable angina is characterized by higher levels of anti-H. pylori IgG but not
      by the higher prevalence of serum IgG interactions with the highly specific and
      specific H. pylori antigens. Such infection could be considered as a cofactor for
      atherogenesis by inducing strong humoral response against surface antigens of
      this bacteria.

PMID- 16450839
TI  - Enzyme production and biotypes of vaginal Candida albicans.
AB  - Candidial vulvovaginitis is one of the most common forms of vaginal infection.
      However, the origin of the infecting organism is sometimes doubtful. Therefore,
      epidemiological investigation can help to recognize routes of infection
      spreading. The aim of the present study was to determine the ability to produce
      esterases by clinical isolates of C. albicans and to find the relationship
      between their serotypes. Also, it was intended to determine the ability of these
      strains to produce proteases and lipases as well as the ability of the strains to
      assimilate carbohydrates. 46 strains of C. albicans isolates from the vagina of
      women suffering from vulvovaginitis were examined. Three main kinds of esterases
      were distinquished by their spectra of hydrolytic activity toward alpha-naphthyl
      acetate, beta-naphthyl propionate and indoxyl acetate. The strains were grouped
      into four categories: three categories in which esterase patterns were observed
      and one category in which esterase bands were not observed. On the basis of the
      20 carbon sources assimilated, the C. albicans strains were categorized into 11
      biotypes with the major biotype accounting for 21 (45.7%) strains. The
      examination of proteolytic activity using casein and albumin enabled to divide
      the strains into four groups. All of the examined strains belonged to serotype A
      and all of them expressed lipolytic activity. Esterase electrophoretic patterns
      and biotypes based on proteolytic activities were compared with the ability to
      assimilate carbon from various sources.

PMID- 16450840
TI  - Purification and characterization of two extracellular lipases from Pseudomonas
      aeruginosa Ps-x.
AB  - Two different extracellular lipases were isolated and purified from Pseudomonas
      aeruginosa Ps-x to apparent homogeneity using ammonium sulfate precipitation
      followed by ion exchange chromatography on Q- and S-Sepharose column. Both of the
      purified lipases are monomeric protein with molecular weight of 15.5 and 54.97
      KDa respectively. The optimal activities of the enzymes were at 45 and 50 degrees
      C and pHs 10.0 and 9.0. Calcium ions increase thermostability of both purified
      lipases I and II. The purified lipase I showed no metal ion dependence for its
      activity since EDTA up to 10 mM has no effect on the enzyme activity. However
      purified lipase II showed slight inhibition by EDTA at the same concentration.
      Moreover, a serine protease inhibitor, PMSF showed an inhibitory effect on both
      purified enzymes.

PMID- 16450841
TI  - Extraction of milk-clotting enzyme produced by solid state fermentation of
      Aspergillus oryzae.
AB  - Studies on the extraction of milk-clotting enzyme after solid-state fermentation
      (SSF) of wheat bran by a local strain of Aspergillus oryzae LS1 were done. The
      extraction of the enzyme was found to be depended on different parameters like
      nature of extractant, soaking time, temperature etc. From different inorganic and
      organic extractants, calcium chloride (0.05%) and glycerol (40%) were found to be
      the best solvents for leaching out milk-clotting enzyme. The optimum volume of
      calcium chloride was 5 ml/g biomass. An extraction time of 180 min. at 30 degrees
      C and 100 rpm was sufficient to extract out nearly 28% of the enzyme (2666.7 U/g
      biomass). Most of the enzyme (about 98.71%) was recovered in four repeated
      extractions.

PMID- 16450843
TI  - Co-occurrence of urogenital mycoplasmas and group B streptococci with chlamydial
      cervicitis.
AB  - The aim of our study was to evaluate whether in women with chlamydial cervicitis
      urogenital mycoplasmas and group B streptococci (GBS) colonization is found more
      often than among women with non-chlamydial cervicitis. This study included 351
      (mean age 31.7 +/- 6.82) not pregnant, menstruating, sexually active women. We
      confirmed a high frequency (49.3%) of C. trachomatis infection among women with
      cervicitis. Cervical ectopia was confirmed in 26.5% of examined women, in half of
      them ectopia was associated with chlamydial infection. We did not notice
      differences in frequency of colonization by urogenital mycoplasmas and GBS among
      women with chlamydial and non-chlamydial cervicitis.

PMID- 16450842
TI  - Cloning and preliminary characterization of a GATC-specific beta2-class DNA:m6A
      methyltransferase encoded by transposon Tn1549 from Enterococcus spp.
AB  - A recent study revealed a subfamily of N6-adenine (m6A) methyltransferases that
      comprises a few functionally studied eukaryotic members acting on mRNA and
      prokaryotic members acting on DNA as well as numerous uncharacterized open
      reading frames. Here, we report cloning and functional characterization of a
      prokaryotic member of this family encoded by transposon Tn1549 from Enterococcus
      spp.

PMID- 16450844
TI  - American College Health Association-National College Health Assessment (ACHA
      NCHA) Spring 2004 Reference Group data report (abridged).
AB  - Assessing and understanding the health needs and capacities of college students
      is paramount to creating healthy campus communities. The American College Health
      Association-National College Health Assessment (ACHA-NCHA) is a survey instrument
      developed by the ACHA in 1998 to assist institutions of higher education in
      achieving this goal. The ACHA-NCHA contains approximately 300 questions assessing
      student health status and health problems, risk and protective behaviors, access
      to health information, impediments to academic performance, and perceived norms
      across a variety of content areas, including injury prevention; personal safety
      and violence; alcohol, tobacco, and other drug use; sexual health; weight,
      nutrition, and exercise; and mental health. Twice a year, the ACHA compiles
      aggregate data from participating institutions in a reference group report for
      data comparison. Results from the Spring 2004 Reference Group (N = 47,202) are
      presented in this article.

PMID- 16450845
TI  - Social norms approaches using descriptive drinking norms education: a review of
      the research on personalized normative feedback.
AB  - College students have been shown to consistently overestimate the drinking of
      their peers. As a result, social norms approaches are effective in correcting
      these misperceived norms to reduce alcohol consumption and alcohol-related
      problems. In this review of literature, the authors critically evaluated the
      effectiveness of personalized normative feedback. In addition, the authors
      reviewed personalized normative feedback interventions and provided suggestions
      for increasing the efficacy of these interventions by making better use of
      salient referent group data.

PMID- 16450846
TI  - Web-assisted instruction for changing social cognitive variables related to
      physical activity.
AB  - The authors examined the efficacy of Web-assisted instruction for promoting the
      use of social cognitive theory (SCT) strategies related to physical activity.
      They recruited college students attending health courses. The authors created 3
      groups (Web-assisted, comparison, and control) based on the course structure. The
      Web-assisted group received information on exercise and fitness and a Web-based
      program (treatment, n = 127); 7 sections received the same exercise and fitness
      information as the treatment condition, but no Web-based program (comparison, n =
      118); and 6 sections received information in unrelated areas (control, n = 178).
      The Web-based program consisted of 9 Web assignments (1 per week) that targeted
      key SCT variables. Satisfaction with the Web-based program was high. Use of self
      regulation strategies was significantly higher at posttest in the treatment group
      than it was in the other groups. Knowledge concerning the skills taught by the
      Web assignments was significantly greater in the treatment group than it was in
      the comparison group. The results of this study demonstrate that a Web-based
      instructional program has a positive impact on knowledge and skills related to
      SCT strategies for changing physical activity behavior.

PMID- 16450847
TI  - Awareness and use of a university recreational trail.
AB  - The purpose of this study was to assess awareness and use of a university
      recreational trail. The authors used an Internet questionnaire developed by the
      university's Institutional Research Department, with questions derived from the
      Environmental Supports for Physical Activity Questionnaire and the National
      College Health Risk Behavior Survey Physical Activity Module. Four hundred and
      sixty-seven undergraduate college students participated. Ninety-one percent of
      students reported being aware of the trail, and 73% reported using the trail.
      Sixty-four percent of students reported seeing signage referring to the
      recreational trail. Sixty-seven percent of the students reported using the trail
      once in the past week, 7% reported using the trail twice in the past week, and
      only 2% of the students reported using the trail more than 3 times in the past
      week. Sixty-two percent reported using the trail with another individual.
      Students who were aware of the trail were more likely to use the trail. However,
      of the individuals who used the trail, the majority only used the trail 1 day a
      week. University programming is needed to increase trail usage among college
      students.

PMID- 16450848
TI  - Development and evaluation of the Sleep Treatment and Education Program for
      Students (STEPS).
AB  - University students report significantly worse sleep quality than the general
      population. Sleep problems are related to increased health concerns,
      irritability, depression, fatigue, and attention and concentration difficulties,
      along with poor academic performance. Clinical research indicates that
      psychoeducational interventions are among the most effective methods for
      improving sleep quality in the general population. Similar studies for university
      students are lacking. In this study, the authors describe the development of the
      Sleep Treatment and Education Program for Students (STEPS) and evaluate its
      effectiveness with a double blind, experimental design. Students in the treatment
      group reported significantly improved sleep quality and sleep hygiene behaviors
      at 6 weeks posttreatment.

PMID- 16450849
TI  - Perceived parental approval of drinking and its impact on problem drinking
      behaviors among first-year college students.
AB  - There is a paucity of research investigating the impact that parents may have on
      college drinking. In this study, the authors investigated the relationship
      between students' perceptions of parent approval of drinking and problem drinking
      occurrence. They conducted a Web-based survey of 265 first-year students living
      on campus during their second semester. The authors used logistic regression to
      examine the relationship between students' perceptions of their mothers' and
      fathers' attitudes toward their drinking, their mothers' and fathers' drinking
      habits, and problem drinking since they had begun college. Sixty-nine percent of
      respondents reported experiencing at least 1 drinking problem. Over one third of
      students perceived that their parents would approve of them drinking
      occasionally. Students perceiving more parental approval for their drinking were
      more likely to report at least 1 drinking problem. Student perceptions of
      parental approval of drinking warrant further investigation as a potentially
      mutable correlate of problem drinking.

PMID- 16450850
TI  - The contribution of Jurgen Lauter to multivariate statistics.

PMID- 16450851
TI  - Establishing efficacy of a new experimental treatment in the 'gold standard'
      design.
AB  - Provided that there are no ethical concerns, the comparison of an active drug
      with placebo in a randomized two-arm clinical trial provides the most convincing
      way to demonstrate the efficacy of a new experimental treatment. However, in a
      placebo-controlled clinical trial it is not sufficient to demonstrate merely a
      statistically significant treatment difference. Regulatory authorities strongly
      recommend to assess additionally whether the observed treatment difference is
      also of clinical relevance. The inherent issue is the necessity of the a priori
      definition of what constitutes a clinically relevant difference in efficacy. This
      problem can be solved in a three-arm study by including an active control group.
      We address the necessary conditions in the gold standard design which allow the
      claim of efficacy for the new treatment with particular focus on assay
      sensitivity.

PMID- 16450852
TI  - On confidence bounds for the ratio of net differences in the "gold standard"
      design with reference, experimental, and placebo treatment.
AB  - The three-arm clinical study including a placebo has been recommended to be the
      preferred study design for the comparison of an experimental treatment relative
      to a reference treatment. In a confirmatory three-arm study multiplicity issues
      arise that are not present in two-arm studies. In the past a successful
      demonstration of superiority of the reference over placebo has been regarded a
      prerequisite validation step for the demonstration of superiority of the
      experimental treatment over placebo. However, for an investigator this last
      comparison is the most critical one. In a clinical study the demonstration of
      superiority of the experimental treatment over placebo is a result of its own
      value and this should therefore not be made dependent on tests that are of higher
      priority in a hierarchical test procedure. This can be achieved through a
      symmetrical formulation of Fieller's method for constructing confidence intervals
      for ratio of the expected values from normally distributed variables. In the
      symmetrical formulation the different meanings of nominator and denominator
      disappear, and simultaneous statements for comparisons between the experimental
      treatment and placebo, reference treatment and placebo, and reference and
      experimental treatment can be made. This is accomplished by moving the discussion
      on confidence sets from the line of real numbers to the unit circle which allows
      representing confidence sectors always as connected sets, gives always simple
      geometrical interpretations, and is easy to be transformed back to the real
      numbers if the traditional calculations behave well. The proposed procedures
      provides additional insight in existing methods but does obviously not answer the
      clinical question whether or not the demonstration of superiority of the
      reference treatment over placebo is a necessary validation step for further
      comparisons.

PMID- 16450853
TI  - A note on including time-dependent covariate in regression model for competing
      risks data.
AB  - Recently, regression analysis of the cumulative incidence function has gained
      interest in competing risks data analysis, through the model proposed by Fine and
      Gray (JASA 1999; 94: 496-509). In this note, we point out that inclusion of time
      dependent covariates in this model can lead to serious bias. We illustrate the
      problems arising in such a context, using bone marrow transplant data as a
      working example and numerical simulations. Practical advices are given,
      preventing the misuse of this model.

PMID- 16450854
TI  - A class of goodness of fit tests for a copula based on bivariate right-censored
      data.
AB  - The copula of a bivariate distribution, constructed by making marginal
      transformations of each component, captures all the information in the bivariate
      distribution about the dependence between two variables. For frailty models for
      bivariate data the choice of a family of distributions for the random frailty
      corresponds to the choice of a parametric family for the copula. A class of tests
      of the hypothesis that the copula is in a given parametric family, with
      unspecified association parameter, based on bivariate right censored data is
      proposed. These tests are based on first making marginal Kaplan-Meier
      transformations of the data and then comparing a non-parametric estimate of the
      copula to an estimate based on the assumed family of models. A number of options
      are available for choosing the scale and the distance measure for this
      comparison. Significance levels of the test are found by a modified bootstrap
      procedure. The procedure is used to check the appropriateness of a gamma or a
      positive stable frailty model in a set of survival data on Danish twins.

PMID- 16450855
TI  - A semi-Markov model based on generalized Weibull distribution with an
      illustration for HIV disease.
AB  - Multi-state stochastic models are useful tools for studying complex dynamics such
      as chronic diseases. Semi-Markov models explicitly define distributions of
      waiting times, giving an extension of continuous time and homogeneous Markov
      models based implicitly on exponential distributions. This paper develops a
      parametric model adapted to complex medical processes. (i) We introduced a hazard
      function of waiting times with a U or inverse U shape. (ii) These distributions
      were specifically selected for each transition. (iii) The vector of covariates
      was also selected for each transition. We applied this method to the evolution of
      HIV infected patients. We used a sample of 1244 patients followed up at the
      hospital in Nice, France.

PMID- 16450856
TI  - Markov modelling of immunological and virological states in HIV-1 infected
      patients.
AB  - The purpose of this study was to evaluate the evolution of HIV infected patients
      and to bring out some significant factors associated with this pathology. The
      main criteria revealing the State of illness is viral load measurement (VL).
      However the CD4 lymphocytes also represent an important marker as these reflect
      the State of the immune reservoir. Many studies have been carried out in this
      field and different models have been proposed with a view to a better
      understanding of this disease. Multi State Markov models defined in terms of CD4
      counts, or in terms of viral load, have proved to be very useful tools for
      modelling HIV disease progression. The model we have developed in this study is
      based on both the CD4 lymphocytes counts and VL. Markov models are characterized
      by transition intensities. In this paper we explored several structures in
      succession. First, we used a homogeneous continuous time Markov process with four
      states defined by crossed values of CD4 and VL in a given patient at a given
      time. Then, the effect of certain covariates on the infection process was
      introduced into the model via the transition intensity functions, as with a Cox
      regression model. Since the hypothesis of homogeneity may be unrealistic in
      certain cases, we also considered piecewise homogeneous Markov models. Finally,
      the effects of covariates and time were combined in a piecewise homogeneous model
      with a covariate. We applied these methods to data from 1313 HIV-infected
      patients included in the NADIS cohort.

PMID- 16450857
TI  - A version of the EM algorithm for proportional hazard model with random effects.
AB  - Proportional hazard models with multivariate random effects (frailties) acting
      multiplicatively on the baseline hazard have recently become a topic of an
      intensive research. One of the main practical problems related to the models is
      the estimation of parameters. To this aim, several approaches based on the EM
      algorithm have been proposed. The major difference between these approaches is
      the method of the computation of conditional expectations required at the E-step.
      In this paper an alternative implementation of the EM algorithm is proposed, in
      which the expected values are computed with the use of the Laplace approximation.
      The method is computationally less demanding than the approaches developed
      previously. Its performance is assessed based on a simulation study and compared
      to a non-EM based estimation approach proposed by Ripatti and Palmgren (2000).

PMID- 16450858
TI  - Calibration of multivariate scatter plots for exploratory analysis of relations
      within and between sets of variables in genomic research.
AB  - The scatter plot is a well known and easily applicable graphical tool to explore
      relationships between two quantitative variables. For the exploration of
      relations between multiple variables, generalisations of the scatter plot are
      useful. We present an overview of multivariate scatter plots focussing on the
      following situations. Firstly, we look at a scatter plot for portraying relations
      between quantitative variables within one data matrix. Secondly, we discuss a
      similar plot for the case of qualitative variables. Thirdly, we describe scatter
      plots for the relationships between two sets of variables where we focus on
      correlations. Finally, we treat plots of the relationships between multiple
      response and predictor variables, focussing on the matrix of regression
      coefficients. We will present both known and new results, where an important
      original contribution concerns a procedure for the inclusion of scales for the
      variables in multivariate scatter plots. We provide software for drawing such
      scales. We illustrate the construction and interpretation of the plots by means
      of examples on data collected in a genomic research program on taste in tomato.

PMID- 16450859
TI  - A note on comparing exposure data to a regulatory limit in the presence of
      unexposed and a limit of detection.
AB  - In some occupational health studies, observations occur in both exposed and
      unexposed individuals. If the levels of all exposed individuals have been
      detected, a two-part zero-inflated log-normal model is usually recommended, which
      assumes that the data has a probability mass at zero for unexposed individuals
      and a continuous response for values greater than zero for exposed individuals.
      However, many quantitative exposure measurements are subject to left censoring
      due to values falling below assay detection limits. A zero-inflated log-normal
      mixture model is suggested in this situation since unexposed zeros are not
      distinguishable from those exposed with values below detection limits. In the
      context of this mixture distribution, the information contributed by values
      falling below a fixed detection limit is used only to estimate the probability of
      unexposed. We consider sample size and statistical power calculation when
      comparing the median of exposed measurements to a regulatory limit. We calculate
      the required sample size for the data presented in a recent paper comparing the
      benzene TWA exposure data to a regulatory occupational exposure limit. A
      simulation study is conducted to investigate the performance of the proposed
      sample size calculation methods.

PMID- 16450860
TI  - Pathogenicity of a local peste des petits ruminants virus isolate in sheep in
      Turkey.

PMID- 16450861
TI  - Ovulatory response and embryo yield in Jakhrana goats following treatments with
      PMSG and FSH.
AB  - Superovulatory response and embryo production efficacy were investigated in adult
      (age 2-4 years, average body weight: 27-43 kg) cycling Jakhrana goats (n = 15)
      under semi-arid environmental conditions of India by administering different
      superovulatory regimens. Goats were reared under semi-intensive system of
      management in established farm conditions. To synchronize oestrus, a luteolytic
      dose of carboprost tromethamine (Upjohn, UK) was administered intramuscularly to
      all does at the dose rate of 5 microg per kg body weight in a double dose
      schedule with an interval of 11 days. For superovulation, 750 IU of PMSG
      (Folligon, Intervet, Boxmeer, Holland) per goat was administered intramuscularly
      24 h before administering a second dose of luteolytic agent in five does
      (treatment 1). FSH (Sigma, St. Louis, MO, USA) 12.50 IU per goat was administered
      intramuscularly in a decreasing daily dose schedule (2.50, 2.50; 1.875, 1.875;
      1.25, 1.25; 0.625, 0.625) at 12 h intervals over four days, initiated 48 h before
      administering second dose of carboprost tromethamine in 5 does (treatment 2). FSH
      (Super-Ov, Ausa Intern, USA) was administered at a uniform dose rate of 8.33
      units per goat intramuscularly at 24 h intervals over three consecutive days
      (total dose was 25 units), initiated 48 h before administering a second dose of
      carboprost tromethamine in 5 does (treatment 3). To synchronize ovulation in
      responders, human chorionic gonadotrophin (hCG, Chorulon, Intervet) was injected
      intramuscularly at a dose rate of 500 IU in each goat on the day of oestrus
      appearance. Goats were laparotomized 72-82 h following the onset of synchronized
      oestrus and their genitalia were flushed using a standard collection procedure.
      Variability (p > 0.05) in superovulatory response (number of established corpora
      lutea) was observed: FSH (Sigma), 11.8 +/- 2.9; FSH (Super-Ov), 11.6 +/- 4.5;
      PMSG (Intervet), 8.4 +/- 2.3. A similar pattern was reflected in mean embryo and
      transferable embryo recovery, respectively (p > 0.05): FSH (Sigma), 8.0 +/- 1.8,
      5.2 +/- 1.7; FSH (Super-Ov), 6.6 +/- 2.4, 5.4 +/- 2.4; PMSG, 5.8 +/- 1.9, 3.8 +/-
      2.2. In PMSG-treated does, comparatively more unfertilized ova or retarded
      embryos were recovered than in FSH-treated does. The superiority of FSH
      preparations over PMSG was reflected in terms of total and transferable embryo
      production (p > 0.05). On average, five transferable embryos (excellent and good
      quality) were recovered per doe treated with FSH of either source. The mean
      ova/embryo recovery was satisfactory (55-68%). Results indicated that Jakhrana
      goats can be superovulated for embryo production using FSH of either source to
      augment productivity.

PMID- 16450862
TI  - Factors affecting fertility according to the postpartum period in crossbred dual
      purpose suckling cows in the tropics.
AB  - To determine the relationship between first service conception rate (FSC) and the
      postpartum period (PP), 6160 calvings from 2250 crossbred dual-purpose cows were
      analysed. The effects of breed predominance (BT: Bos taurus and BI: Bos indicus),
      season of service (dry, intermediate and humid), parity (1 or 2 and more),
      agroecological region (Sub-humid and Dry Tropical Forest) and milk production
      were studied. The postpartum period was grouped according to the calving-first
      service interval as G1 < or = 60 days (n = 1889); G2 > 60 < or = 90 days (n =
      1436); G3 > 90 < or = 120 days (n = 1030); and G4 > 120 days (n = 1805). Data
      were analysed by chi-squared test. The overall mean for FSC was 58.2% and was
      lower in G1 (p < 0.01). All PP showed a breed effect on FSC, with mean values of
      61.6% and 53.3% for BI and BT, respectively. Season of service also affected FSC,
      which was significantly lower during the humid period: 51.2% versus 57.4% and
      61.5% for the intermediate and dry periods (p < 0.01), respectively. Parity and
      environmental effects were not observed on FSC. Levels of milk yield did
      influence the FSC, which decreased from 66.7% and 61.0% for milk yields of < 1500
      kg and between 1501 and 2000 kg to 46.0% in milk yields > 2000 kg (p < 0.01).

PMID- 16450863
TI  - Effect of scavenging and supplementation of lysine and methionine on the feed
      intake, performance and carcase quality of improved dual-purpose growing
      chickens.
AB  - An experiment was conducted with 192 improved dual-purpose chickens from 4 to 12
      weeks of age to evaluate the effects of management system (confinement and
      scavenging) and amino acid supplementation (with and without lysine and
      methionine) of a low-protein diet on the feed and nutrient intake, performance
      and carcase quality of improved chickens. Mean daily dry matter (DM), crude
      protein and metabolizable energy intakes were higher for the confined birds (65
      g, 13.3 g and 966 kJ, respectively) than for the scavenging birds (58 g, 12.0 g
      and 868 kJ, respectively) (p < 0.001) and higher for the unsupplemented (63.3 g,
      13.0 g and 945 kJ, respectively) than for the supplemented birds (59.5 g, 12.2 g
      and 889 kJ, respectively) (p < 0.001). Mean DM intake was 68.0 and 54.9 g/day for
      the males and females (p < 0.001), respectively. Average daily weight gains (ADG)
      were higher for scavenging (26.9g) than for confined birds (23.9g) (p < 0.001),
      higher for supplemented (27.6 g) than for unsupplemented birds (23.2 g) (p <
      0.001) and higher for males (27.5 g) than for females (23.3 g) (p < 0.001).
      Carcase, breast and thigh percentages were higher for supplemented than for
      unsupplemented birds (p < 0.001) and higher for scavenging than for confined
      birds (p < 0.001). Abdominal fat percentage was significantly lower for the
      scavenging treatments compared to the corresponding confined treatments (p <
      0.001). Feed conversion ratios (kg feed/kg gain) and feed costs/kg gain were
      lower for the scavenging than for the confinement treatments, and lower for the
      supplemented than for the unsupplemented birds (p < 0.001). Supplementation of
      lysine and methionine in diets that were suboptimal in terms of protein and
      essential amino acids improved performance and carcase quality and reduced feed
      costs, in particular of the confined growers.

PMID- 16450864
TI  - Economic contribution of draught animals to Mazahua smallholder Campesino farming
      systems in the highlands of Central Mexico.
AB  - The economic contribution of draught animals to smallholder Mazahua campesino
      systems in two mountain villages of San Felipe del Progreso, in the central
      highlands of Mexico, was assessed. Campesinos rely on draught animals for
      cultivation tasks, as pack animals, and as transport for agricultural and
      domestic activities. The villages were San Pablo Tlalchichilpa (SPT) and La
      Concepcion Mayorazgo (LCM). Twelve households that possessed draught animals were
      monitored from July 1999 to June 2000, nine in SPT and three in LCM, in terms of
      animal inventories and income from their draught animals, in cash and opportunity
      values. Equines in SPT have substituted bulls, and are recognized for their
      multipurpose contribution, while in LCM bulls are still used for ploughing the
      land. Overall total mean gross income was US dollar 490.78 per farm per year,
      plus US dollar 56 as opportunity value of the fertilizer value of manure for both
      villages. Deducting estimated costs, owning draught animals leaves a mean net
      margin of US dollar 412.50/year in SPT and of US dollar 285.64/year in LCM. There
      is a significant correlation (p < 0.05) between ownership of draught animals and
      incomes, with a regression coefficient of US dollar 279.16 per year per draught
      animal. Besides positive economic returns, having work animals alleviates
      drudgery for the campesino families.

PMID- 16450865
TI  - Fluorescent antibody-viability staining and beta-glucuronidase assay as rapid
      methods for monitoring Escherichia coli viability in coastal marine waters.
AB  - A faecal pollution monitoring of coastal Messina waters was performed by
      comparing three (microscopic, enzyme, and culture) methods. Evidence of
      Escherichia coli cells (29.99 to 96.79% of the total enteropathogenic serotypes)
      retaining their viability into the marine environment was shown. beta
      Glucuronidase activity rates suggested that living cells were also metabolically
      active. Heavily polluted sites were detected, where improperly treated urban
      wastes were discharged. Significant relationships between microscopic and
      enzymatic data proved both methods to be suitable alternatives to the culture
      method for E. coli detection, improving environmental quality assessment.

PMID- 16450866
TI  - Development of colorimetric enzyme-linked immunosorbent assay for human chorionic
      gonadotropin.
AB  - The present study demonstrated the development of a solid phase competitive
      enzyme linked immunosorbent assay (ELISA) for direct estimation of human
      chorionic gonadotropin (hCG) in serum and urine. Polyclonal antisera raised
      against the beta- subunit of peak-I hCG was used in the assay. The Peak-IA hCG
      penicillinase was used as tracer. The performance of this antiserum and tracer
      was compared against hCG-beta antisera of NIH, USA and penicillinase conjugated
      to hCG-beta obtained from NIH, respectively. Almost parallel standard curves were
      obtained in both cases, suggesting that these antisera and enzyme label have much
      potential for developing ELISA system. To the anti-rabbit gamma globulin (ARGG)
      coated polystyrene tubes, standard or serum or urine samples (50 microL), 100
      microL of hCG-beta antiserum, 100 microL of peak-I(A) hCG-penicillinase conjugate
      and 350 microL of assay buffer were incubated at 37 degrees C for 2 hours. Bound
      enzyme activity was measured using Penicilline V as substrate. In this new
      strategy, locally available polystyrene tubes were ground from inside and coated
      with ARGG. The sensitivity of the assay was 17 mIU/mL in urine and 18 mIU/mL in
      serum. The intra-assay and inter-assay coefficients of variation (CVs) appeared
      to be within acceptable limits of 10%. The serum and urinary hCG values, obtained
      by this method, correlated well with those obtained by radioimmunoassay (RIA) r =
      0.98 (n = 100 for serum samples; n = 250 for urinary samples).

PMID- 16450867
TI  - A quantitative nitroblue tetrazolium assay for determining intracellular
      superoxide anion production in phagocytic cells.
AB  - Conventionally, a semi-quantitative microscopic nitroblue tetrazolium (NBT) assay
      is used to determine the production of superoxide anion (O2(-)) in various
      phagocytic cells. This microscopic assay is conducted by counting the cells
      containing blue NBT formazan deposits, which are formed by reduction of the
      membrane permeable, water-soluble, yellow-colored, nitroblue tetrazolium (Y-NBT)
      by O2(-). However, this assay is semi-quantitative and is prone to observer bias.
      In the present study, we modified the NBT assay by dissolving the blue formazan
      particles using 2M potassium hydroxide and dimethylsulfoxide and then measured
      its absorbance using a microplate reader at 620nm. The absorbance of dissolved
      NBT increased in proportion to cell number (r = 0.9907), incubation time, and
      stimulus concentration. To test the usefulness of this modified assay, we
      compared the abilities of a number of types of phagocytic cells to produce O2(-).
      The cells examined included murine macrophage cell lines (RAW 264.7 and J774),
      freshly prepared murine peritoneal macrophages and neutrophils, a human myeloid
      cell line (PLB-985), and freshly prepared human peripheral blood neutrophils. In
      addition, we demonstrate that nitric oxide produced by RAW 264.7 cells does not
      interfere with the modified colorimetric NBT assay. Taken together, our results
      indicate that the modified colorimetric NBT assay is simple, sensitive, and
      quantitative, and that it can be used to determine the amounts of intracellular
      O2(-) produced by phagocytic cells. Thus, this assay is sensitive enough to
      measure, quantitatively, even the small amounts of O2(-) produced in monocytes
      and macrophages that are not detectable by the conventional microscopic NBT
      assay.

PMID- 16450868
TI  - Immunochemical identification and detection of a 36-kDa Toxoplasma gondii
      circulating antigen in sera of infected women for laboratory diagnosis of
      toxoplasmosis.
AB  - The detection of Toxoplasma gondii circulating antigens has been indicated to be
      a reliable diagnostic approach of active human toxoplasmosis. However, few
      reports have appeared in the literature regarding the diagnostic potential of T.
      gondii circulating antigens. Here, a specific antibody and western blot analyses
      were used to demonstrate the presence of a highly reactive antigen of 36-kDa, not
      only in the extract of T. gondii tachyzoites, but also in selected sera of women
      with confirmed laboratory and clinical signs of recent toxoplasmosis. The 36-kDa
      Toxoplasma antigen was purified from T. gondii tachyzoites and human serum using
      electroelution from preparative polyacrylamide gels. The purified polypeptides
      showed a single peak at 10.9 min when analyzed by capillary zone electrophoresis.
      Based on the above encouraging results, we have developed an ELISA format for the
      detection of target Toxoplasma antigen (TAg-ELISA) in human serum samples. The
      TAg-ELISA detected the target antigen in 88% sera of acutely infected women and
      showed high degree of specificity (91%) among sera from non-infected women. In
      conclusion, the detection of 36-kDa Toxoplasma circulating antigen in human sera
      appears to be a promising alternative approach for laboratory diagnosis of active
      T. gondii infection.

PMID- 16450869
TI  - Impact of different cell isolation techniques on lymphocyte viability and
      function.
AB  - The outcome of immunological assays is markedly influenced by the method of
      isolation of lymphocytes. It is, therefore, important to comparatively assess
      various techniques of isolation of lymphocytes, an aspect thus far not thoroughly
      addressed. In particular, the potential of isolation techniques to influence cell
      recovery, viability, and function has not yet been evaluated. These studies were
      designed to determine the effect of different mechanical tissue dissociation
      methods on the viability and function of lymphocytes. Following spleen and thymus
      removal, the lymphoid organs were dissociated by one of four different tissue
      dissociation techniques: metallic screen, sheer force slide, commercial
      stomacher, or plunger-screen. Cells were then enumerated and a trypan blue
      exclusion technique and 7-amino-actinomycin D (7-AAD) were both employed to
      assess viability. Mitogen-induced lymphocyte proliferation was measured using the
      Alamar Blue assay. Cell viability and lymphocyte surface antigen expression were
      assessed using flow cytometry. No significant differences in lymphocyte
      viability, morphology, or surface antigen expression were observed among the
      different techniques. Likewise, cellular apoptosis and necrosis were comparable
      across all the techniques. However, mitogen induced splenic T-cell proliferation
      was higher in cells collected using the metallic screen and plunger-screen
      isolation methods as compared to the sheer force slide or commercial stomacher
      procedures. These data suggest that cell recovery, morphology, and viability are
      not affected by isolation techniques. However, lymphocyte function, as assessed
      by mitogen induced proliferation, was negatively affected by the sheer force
      slide or commercial stomacher isolation techniques.

PMID- 16450870
TI  - Optimized flow cytometric analysis of endothelial progenitor cells in peripheral
      blood.
AB  - Although flow cytometry is a rapid and convenient way to measure the number of
      circulating endothelial progenitor cells (EPC), there is no standard technique
      for preparation and measurement. The aim of this study was to present an
      optimized preparation method for EPC measurement which should serve as a standard
      to facilitate the comparison of the results in stem cell investigations by
      different research groups. We have looked for the preparation method which
      delivered the best immunostaining with the directly conjugated antibodies against
      VEGF R2, CD133, CD34, and CD45. In order to test the sensitivity of the method,
      we determined the number of EPC in the peripheral blood of volunteers by flow
      cytometry and by cell culture assay. Furthermore, we have evaluated the influence
      of different durations of conservation on the EPC cell count. The pre-treatment
      of blood samples with 0.2% formaldehyde for 30 minutes delivers the best
      immunostaining, and blood samples can be stored overnight at 4 degrees C without
      loss of counting rate for EPC. We found an excellent correlation (r = 0.98)
      between the flow cytometric measurement and the cell count of the cell culture
      method. The presented protocol for the flow cytometric measurement of EPC in the
      peripheral blood can be used as a diagnostic or prognostic tool; we propose this
      protocol as the standard for EPC quantification.

PMID- 16450871
TI  - Change in immunoreactive human hepatic triglyceride lipase (HTGL) mass and the
      shelf-life of the HTGL ELISA kit in long-term storage.
AB  - Objectives of this work are to study changes in the immunoreactive HTGL mass
      during storage under various conditions. In addition, the shelf-life of the HTGL
      ELISA kit was confirmed. The immunological reactivity of HTGL in PHP stored in
      the liquid, frozen, or lyophilized state was monitored using purified human PHP
      HTGL as the standard material. Furthermore, the long-term stability of the HTGL
      ELISA kit was ascertained. The immunoreactive HTGL mass in the lyophilized PHP
      maintained its initial immunological reactivity for at least 26 months at 4
      degrees C or lower. The other reagents included in the HTGL ELISA kit also have a
      long shelf-life when they are stored at 4 degrees C or less. HTGL in PHP was
      stabilized by lyophilization and can be used as the standard material for HTGL
      ELISA; the HTGL ELISA kit has a long shelf-life, i.e., more than two years.

PMID- 16450872
TI  - Distinct serum immunoglobulins pattern in Egyptian patients with chronic HCV
      infection analyzed by nephelometry.
AB  - Hepatitis C has emerged as a major worldwide public health problem. The host
      immune response to HCV infection is composed of both a non-specific immune
      response, including interferon (IFN) production and natural killer (NK) cell
      activity, and a virus-specific immune response, including humoral and cellular
      components. Susceptibility to infection has been related to immunological
      disturbances. Several studies have provided experimental evidence of disorders of
      both cellular and humoral immunity. The present study was carried out to evaluate
      the serum immunoglobulins level (IgG, IgM, IgA) and IgG-subclasses (IgG1-4) in
      chronic hepatitis C patients in comparison with healthy control patients. This
      study included 50 patients with biochemical, serologic, virologic, and histologic
      evidence of chronic hepatitis C. Total IgG, IgA, and IgM were assayed by
      nephelometry. IgG subclasses were assayed using human IgG subclasses enzyme
      immunoassay. The results showed a significant increase of total serum IgG and IgM
      levels found in patients with chronic HCV compared with the healthy control
      patients (P < 0.001 for each). There was a statistically significant difference
      in the IgG subclasses (IgG1 to IgG4) between the patients and controls (P < 0.001
      for each). On the other hand, no significant difference was found between
      patients and healthy controls in IgA level (P = 0.4). The normal total serum
      immunoglobulins pattern is apparently shifted in chronic hepatitis C infection in
      the Egyptian patients. This pattern may include an ethnic or biologic background
      and could be used in the differentiation of the patients with minimal liver
      disease.

PMID- 16450873
TI  - Investigating euthanasia: methodological, ethical and clinical considerations.

PMID- 16450874
TI  - Differences between terminally ill cancer patients who died after euthanasia had
      been performed and terminally ill cancer patients who did not request euthanasia.
AB  - Palliative care, directed at improving the quality of life of terminally ill
      patients, is generally not aimed at any form of postponing or hastening death. It
      is possible that high quality palliative care could prevent requests for
      euthanasia. However, empirical evidence on this issue is scarce. In a national
      survey of end-of-life medical decisions in The Netherlands the subject of care at
      the end of life has been addressed. Data on terminally ill cancer patients who
      died after their request was granted and euthanasia had been performed were
      compared with those of terminally ill cancer patients who did not request
      euthanasia. The results show that the prevalence and severity of symptoms e.g.,
      pain, feeling unwell, nausea, was higher in patients who died after their request
      was granted and euthanasia had been performed. No differences concerning the
      treatment of symptoms or the care provided were found between the two groups. The
      results suggest that the practice of euthanasia is mainly related to the
      patient's suffering.

PMID- 16450875
TI  - The demand for euthanasia in palliative care units: a prospective study in seven
      units of the 'Rhone-Alpes' region.
AB  - A prospective survey of five palliative care units in the Rhone-Alpes region of
      France over a six-month period identified 13 requests for euthanasia (from the
      patient, family or both). The frequency of the request was low at 2.1% (of 611
      patients). We have sought to establish the reasons for this request from the
      patient or family and the follow up of this request over time.

PMID- 16450876
TI  - Receiving bad news: patients with haematological cancer reflect upon their
      experience.
AB  - The literature on breaking bad news (BBN) tends to focus on professional
      consensus rather than empirical patient evidence--the 'giver' rather than the
      'receiver'. Using semi-structured interviews, this study explores the experiences
      of patients with haematological cancer as they reflect on the process and content
      of receiving bad news. Fifteen patients with a diagnosis of leukaemia or lymphoma
      were recruited through a haematology service during a routine clinical visit,
      with the decision to participate being made later. Interviews were audiotaped,
      transcribed and analysed using thematic content analysis. Patients place
      importance on not being rushed during the bad news consultation and the doctor's
      manner. Receiving bad news was the first step on a journey, not an isolated
      incident. Doctors were regarded as the best judge of their information needs,
      with leaflets and written summaries as supplements. Patients had strong
      preferences about continuity and language use. Displays of empathy were
      important, but must be genuine. Patients wanted to know about likely emotional
      reactions and future support. Where patients brought a companion, they found this
      valuable. Patients concur with much of the content of the guidelines, but place
      more emphasis on their illness journey, the doctor's ability to adapt to their
      emotional needs, language used, information leaflets, having a companion and
      genuinely personalizing the approach. Reflection on these patient-derived factors
      may help health professionals better serve patients with serious illness.

PMID- 16450877
TI  - Being a hospice volunteer.
AB  - The aim of this study was to obtain an understanding of what it means to be a
      hospice volunteer in a country without a tradition of hospice or palliative
      volunteer care services. Ten volunteers from three different hospices in Sweden
      were interviewed. Their narratives were interpreted with a phenomenological
      hermeneutic method. Three themes were disclosed: motives for becoming involved in
      hospices, encountering the hospice and encountering the patient. The
      interpretations disclose a need for the volunteer to be affirmed as a caring
      person and received in fellowship at the hospice. Positive encounters with a
      hospice are closely related to personal growth. Volunteers feel rejected if their
      need for meaning and for belonging to the hospice is not satisfied. This shows
      that hospices need to set goals in terms of volunteer support, particularly
      regarding existential issues following the encounter with the hospice and the
      patient.

PMID- 16450878
TI  - An exploration of family carers' experience of respite services in one specialist
      palliative care unit.
AB  - BACKGROUND: Changing patterns of care for terminally ill people mean that 90% of
      patients in the UK now spend the majority of their last year of life at home. It
      is now widely accepted that supporting individuals to die at home relies heavily
      on the availability of family carers to provide the majority of the care needed.
      However, one of the most common reasons for unplanned admissions near the end of
      life is carers' inability to provide continuing care. One strategy to overcome
      these challenges has been to offer planned respite care. Despite recent studies,
      in reality little is known about respite services for patients with life limiting
      illness, in particular how respite is experienced by the caregivers or to what
      extent respite services address their needs. METHODS: This prospective study,
      comprising mixed methods of data collection, explored the experiences of 25
      family carers whose relative had been admitted to the local hospice for inpatient
      respite care. Semi-structured interviews were conducted at two time points: pre-
      and post-respite. The Relative Stress Scale Inventory was administered at both
      interviews. RESULTS: Just over half of the sample were caring for a relative with
      a diagnosis of cancer (n=13); the majority of the others had a number of
      neurological conditions (n = 12). The data demonstrate that managing care for
      relatives with a life limiting illness was perceived to be hard work, both
      physically and mentally. Inpatient respite care was considered important as it
      enabled family carers to have a break from the ongoing care-giving
      responsibilities, as well as being an opportunity to experience 'normal life'
      independently. The majority of family carers felt that their expectations of
      respite for themselves had been achieved. The respite service was well evaluated
      in relation to: standard of nursing care; alternative facilities on offer,
      atmosphere; and other care homes. DISCUSSION: Currently, inpatient respite
      services are provided to two patient groups--those in the last year of life and
      those with a chronic life limiting illness. However, on closer analysis, the
      current model of service delivery, a two-week inpatient stay, may not be best
      suited to those caring for a relative in the last year of life. Similarly, it
      might be questioned whether an inpatient hospice is the most suitable setting for
      those patients needing supportive care, rather than specialist palliative care.
      The study has raised many issues that need to be considered in the support of
      carers caring for relatives with a life limiting illness with uncertain
      trajectories.

PMID- 16450879
TI  - 'Now nobody falls through the net': practitioners' perspectives on the Gold
      Standards Framework for community palliative care.
AB  - The Gold Standards Framework (GSF) seeks to facilitate consistent and high
      quality community palliative care through a set of guidelines, mechanisms and
      assessment tools. The present study set out to examine practitioners'
      perspectives on the GSF during its first national roll-out. Two general practices
      that had adopted the GSF were recruited in each of four geographical areas, and
      each matched as closely as possible with a non-GSF practice. Sixty-eight semi
      structured telephone interviews were carried out with general practitioners and
      district nurses in 16 selected practices, along with the GSF facilitator and up
      to four other 'stakeholders' in each area. Analysis revealed that the majority of
      GSF participants felt that the framework had strengthened their provision of
      community palliative care. In particular, communication within primary health
      care teams and co-ordination of services improved, aspects which were better in
      the GSF practices than in the matched non-GSF practices. Practitioners felt there
      was more consistency of care, with a reduced likelihood that individual patients
      would 'slip through the net'. The most common areas of concern were in relation
      to the workload associated with the role of the GSF co-ordinator. Implications
      for the development and effective implementation of the framework and for further
      research are discussed.

PMID- 16450881
TI  - Clinical notes for informal carers in palliative care: recommendations from a
      random patient file audit.
AB  - Although palliative care aims to support family members and informal carers,
      current evidence suggests that high levels of unmet need persist, and that this
      population is challenging to work with. This study aimed to 1) measure the
      proportion of patients that have an informal carer, 2) describe the clinical
      notes data on existing needs and coping, 3) measure the completeness of
      assessment data recording, 4) appraise the utility of existing informal carers'
      sections in the patient files, and 5) make recommendations for improvement. An
      audit was conducted reviewing 145 closed patient files. Of these, 100 had
      identifiable informal carers (69.9%). Although patient data was complete, data
      was severely lacking on their informal carer. Diverse coping strategies were
      described, and the primary need was for finance and advice about state welfare
      payments (n=64). The findings suggest a need for files to identify and record
      informal carers as potentially distinct from family members, promote assessment
      data completion for informal carers on a par with that of patients, and to
      develop systematic approaches to systems that maximize utility and incorporate
      multiprofessional input into the development of clinical notes.

PMID- 16450880
TI  - The last three months of life of Italian cancer patients. Methods, sample
      characteristics and response rate of the Italian Survey of the Dying of Cancer
      (ISDOC).
AB  - STUDY OBJECTIVE: The Italian Survey of the Dying of Cancer (ISDOC) was undertaken
      to evaluate the experiences of Italian people dying from cancer during their last
      three months of life in all settings of care. STUDY DESIGN: A two-stage
      probability sample was used to estimate end-of-life outcomes of about 160 000
      Italian cancer deaths. In the first stage, 30 of the 197 Italian Local Health
      Districts (LHD) were randomly selected after stratification. In the second stage,
      a fixed proportion of cancer deaths was randomly drawn from each LHD, and 2000
      death certificates of patients who died of cancer were identified. The non
      professional caregivers were identified and interviewed using a semi-structured
      questionnaire derived from the Views of Informal Carers--Evaluation of Services
      (VOICES). RESULTS: Caregivers were successfully identified for 95% of the sample
      (n=1900). The caregiver was the child (42.7%), the spouse (36.5%), another family
      member (17.3%), or a friend (1.5%). Only 3% of the sample had no non-professional
      support. An interview was obtained for 1289 (64.5%) of the sample, at a median
      time of 234 days after death (range: 103-374). Higher response rates were
      associated with home death (67.7%) and with a higher education (>70%).
      Conversely, a lower response rate was observed when the caregiver was the spouse
      (56.2%). Response rates ranged from about 80% for letters sent four to six months
      after the patients' death to about 60% for letters sent after eight months or
      more. A descriptive analysis of refusals, based on the transcripts of the
      telephone calls, allowed classification of 61% of refusals for at least one of
      the two dimensions examined: caregiver psychological suffering and quality of
      care received by the patient. Psychological suffering was present in 99% of
      refusals examined for this dimension (48%). Conversely, a poor quality of care
      was reported by 63% of the refusals examined for this dimension (23%).
      CONCLUSION: The ISDOC survey provides a representative picture of the needs and
      problems associated with the last three months of life of Italian cancer
      patients.

PMID- 16450882
TI  - Quorum sensing and the lifestyle of Yersinia.
AB  - Bacterial cell-to-cell communication ('quorum sensing') is mediated by
      structurally diverse, small diffusible signal molecules which regulate gene
      expression as a function of cell population density. Many different Gram-negative
      animal, plant and fish pathogens employ N-acylhomoserine lactones (AHLs) as
      quorum sensing signal molecules which control diverse physiological processes
      including bioluminescence, swarming, antibiotic biosynthesis, plasmid conjugal
      transfer, biofilm development and virulence. AHL-dependent quorum sensing is
      highly conserved in both pathogenic and non-pathogenic members of the genus
      Yersinia. Yersinia pseudotuberculosis for example, produces at least eight
      different AHLs and possesses two homologues of the LuxI family of AHL synthases
      and two members of the LuxR family of AHL-dependent response regulators. In all
      Yersinia species so far examined, the genes coding for LuxR and LuxI homologues
      are characteristically arranged convergently and overlapping. In Y.
      pseudotuberculosis AHL-dependent quorum sensing is involved in the control of
      cell aggregation and swimming motility, the latter via the flagellar regulatory
      cascade. This is also the case for swimming and also swarming motility in
      Yersinia enterocolitica. Howeverthe role of AHL-dependent quorum sensing in
      Yersinia pestis remains to be determined.

PMID- 16450883
TI  - Antimicrobial peptide resistance mechanisms of human bacterial pathogens.
AB  - The critical role played by antimicrobial peptides (AMPs) in mammalian innate
      immunity is increasingly recognized. Bacteria differ in their intrinsic
      susceptibility to AMPs, and the relative resistance of some important human
      pathogens to these defense molecules is now appreciated as an important virulence
      phenotype. Experimental analysis has identified diverse mechanisms of bacterial
      AMP resistance including altered cell surface charge, active efflux, production
      of proteases or trapping proteins, and modification of host cellular processes.
      The contribution of these resistance mechanisms to pathogenesis is confirmed
      through direct comparison of wild-type bacteria and AMP-sensitive mutants using
      in vivo infection models. Knowledge of the molecular basis of bacterial AMP
      resistance may provide new targets for antimicrobial therapy of human infectious
      diseases.

PMID- 16450884
TI  - The role of tyrosine phosphorylation in regulation of signal transduction
      pathways in unicellular eukaryotes.
AB  - The review summarizes for the first time the current concepts of the role of
      tyrosine phosphorylation in regulation of signal transduction pathways in
      unicellular eukaryotes. Evolutionary concepts are developed about the origin of
      protein tyrosine kinases (PTK)-signaling.

PMID- 16450885
TI  - Ligand-responsive transcriptional regulation by members of the MarR family of
      winged helix proteins.
AB  - The MarR (multiple antibiotic resistance regulator) family of prokaryotic
      transcriptional regulators includes proteins critical for control of virulence
      factor production, bacterial response to antibiotic and oxidative stresses and
      catabolism of environmental aromatic compounds. Recognition of the adaptive
      cellular responses mediated by MarR homologs, and the clinical isolation of
      antibiotic-resistant bacterial strains harboring MarR mutations, has garnered
      increasing medical and agricultural attention to this family. MarR proteins exist
      as homodimers in both free and DNA-bound states. Sequence specific DNA-binding to
      palindromic or pseudopalindromic sites is mediated by a conserved winged helix
      fold and, for numerous homologs, this association is attenuated by specific
      anionic lipophilic ligands. The mechanism of ligand-mediated allosteric control
      of DNA binding is unique amongst prokaryotic transcriptional regulators in that
      the DNA- and ligand-binding domains almost completely overlap in the residues
      involved. Until recently, our understanding of ligand-binding has been limited to
      a MarR-salicylate co-crystal structure, with little information on the allosteric
      mechanisms linking ligand-recognition and DNA-binding. However, recent
      biochemical and biophysical data on MarR homologs have begun to resolve the
      mechanisms by which these proteins mediate ligand-responsive transcriptional
      control.

PMID- 16450886
TI  - This spud's for you.

PMID- 16450887
TI  - Service leadership.

PMID- 16450888
TI  - Health hazard?

PMID- 16450889
TI  - Go the distance.

PMID- 16450890
TI  - Batter up.

PMID- 16450891
TI  - Strength in numbers.

PMID- 16450892
TI  - Partners by proxy.

PMID- 16450893
TI  - Gateway to the web.

PMID- 16450894
TI  - Easy writer.

PMID- 16450895
TI  - Beyond the call.

PMID- 16450896
TI  - Applications of fluorescence in situ hybridization in cytopathology: a review.
AB  - Fluorescence in situ hybridization (FISH) is a molecular cytogenetic technique
      that is a powerful and versatile research tool and an important adjunct to tumor
      diagnosis and prognosis. Akin to the recent role of immunohistochemistry,
      research and clinical applications of FISH in cytopathology have been growing
      enormously over the last few years. Furthermore, due to its feasibility for
      virtually all types of cytologic specimens, a new and exciting era in both
      investigative and clinical cytopathology is expected.

PMID- 16450897
TI  - Sensitivity of HPV tests on stained vs. unstained cervical smears.
AB  - OBJECTIVE: To examine the effect of Pspanicolaou staining of cervical smears on
      the sensitivity of molecular biologic HPV tests. STUDY DESIGN: Two sensitive HPV
      tests were used, HPV DNA sequence analysis after polymerase chain reaction (PCR)
      amplification and the Hybrid Capture II method (HC II) (Digene Diagnostics Inc.,
      Silver Spring, Maryland, USA). Papanicolaou-stained and unstained smears taken
      simultaneously were examined from 265 women readmitted for examination due to an
      atypical squamous cells of undetermined significance diagnosis. RESULTS: After an
      HPV test with the PCR method on unstained slides, 66% of the women were HPV
      positive, whereas the same women were HPVpositive in 54% when Papanicolaou
      stained slides were analyzed. However, this difference was not statistically
      significant (p > 0.1). With the HC II method, 55% of unstained smears were HPV
      positive whereas 29% were HPV positive, when Papanicolaou-stained slides were
      examined. This difference was significant (p < 0.001). The same strong
      differences in sensitivity were observed when both the PCR and HC II methods were
      studied on the same Papanicolaou stained glass slides, whereas on unstained
      slides no significant difference was found. CONCLUSION: The results demonstrate
      that Papanicolaou staining of a cervical smear significantly decreases the
      sensitivity of an HPV test performed with the HC II method, whereas the PCR
      method is less affected. With the Papanicolaou method, the hematoxylin bath is
      followed by HCl treatment, and strong acid treatment destroys DNA.

PMID- 16450898
TI  - Utility of papanicolaou stain-induced fluorescence in the cytodiagnosis of
      extrapulmonary tuberculosis.
AB  - OBJECTIVE: To study the utility of Papanicolaou stain-induced fluorescence (PIF)
      in the detection of tubercle bacilli and to compare its diagnostic efficacy with
      that of the conventional Ziehl-Neelsen (ZN) method. STUDY DESIGN: This
      prospective study was carried out at a tertiary health care center, over a period
      of 2 years between January 2001 and December 2002. A total of 500 cases offine
      needle aspiration cytology from lymph nodes and other extrapulmonary sites were
      studied. Only cases that were clinically and cytologically suggestive of
      tuberculosis were included in the study. The smears were stained with ZN and
      Papanicolaou stain and examined under light and fluorescence microscopes,
      respectively for detection of acid-fast bacilli (AFB). Mycobacterial culture was
      used as the gold standard to compare the results. RESULTS: Cytologic smears were
      categorized into 4 distinct cytomorphologic patterns: epithelioid granulomas
      without caseous necrosis (101 cases), epithelioid granulomas with caseous
      necrosis (268 cases), caseation or acute inflammatory exudate only (114 cases),
      and occasional epithelioid cells without necrosis or giant cells (17 cases). The
      overall AFB positivity was 30.8% with the ZN method, while it was 40.6% with PIF.
      Moreover, PIF was more effective in detecting bacilli in group I lesions (18.8%
      vs. 6.9% with ZN method), in which the bacillary load is very low. CONCLUSION:
      PIF is superior to the conventional ZN method in detecting tubercle bacilli,
      particularly when the bacillary load is low. It is a relatively inexpensive and
      fast technique.

PMID- 16450899
TI  - Cytologic evaluation of prognostic markers in breast carcinoma.
AB  - To type breast carcinomaon on fine needle aspiration cytology (FNAC) material and
      correlate the results with histologic typing, to grade breast carcinoma on FNAC
      material and correlate the findings with Bloom-Richardson histologic grading, and
      to determine the estrogen receptor (ER) status in cases of breast carcinoma by
      immunocytochemical (ICC) staining of FNA cytologic material and correlate the
      findings with ER status, as determined by immunohistochemical (IHC) staining of
      tissue sections. STUDY DESIGN: Seventy-seven cases of breast carcinoma diagnosed
      on FNAC formed the basis of this study. Typing was done in all cases on the basis
      of cytologic features and grading in 62. (Fifteen cases were special types of
      breast carcinoma). In all cases, ER status was determined by immunostaining of
      cytologic smears. Results of tumor typing, grading and ER status on cytologic
      material were compared with the results of histologic typing, grading and
      immunostaining of histologic material obtained from mastectomy or wide excision
      specimens. RESULTS: Tumor typing was accurate in 73 of 77 cases (94.8%). Fifteen
      of 18 cases that were cytologically grade 3 were confirmed on histology, while 3
      proved to be grade 2. Of 40 cytologic grade 2 cases, 26 were confirmed on
      histology, while 14 cases were grade 3. Three of 4 cytologically grade 1 cases
      were confirmed on histology while 1 was grade 2. The overall accuracy for
      cytologic grading was 71% (44 of 62 cases). Thirty-seven of 40 ER-positive cases
      (92.5%) were labeled ER positive on ICC. One case was ER negative on cytology,
      while in 2 cases the cellularity of the cytologic smear was insufficient to
      assess ER expression. Thirty-seven cases were negativefor ER on IHC. Nine of
      these showed ER positivity on ICC, 26 were negative, and 2 had cellularity that
      was inadequate for assessment of ER. Sensitivity and specificity rates for ER
      detection on ICC were 97.4% and 74.3%, respectively. CONCLUSION: Tumor typing,
      grading and evaluation of ER status on FNA C material in breast carcinomas are
      simple, quick and moderately reliable techniques that compare and correlate
      favorably with histologic typing, grading and ER status on IHC.

PMID- 16450900
TI  - Two cytologic patterns in invasive ductal adenocarcinoma of the pancreas.
AB  - OBJECTIVE: To clarify 2 cytologic patterns: severe ductal dysplasia
      (SD)/carcinoma in situ (CIS) and invasive components of invasive ductal
      adenocarcinoma of the pancreas (IDAP). STUDY DESIGN: Tumor samples from 12
      patients with IDAP were examined cytologically and histologically. Cytologic
      specimens were obtained by fine needle aspiration (ENA) and imprint smears from
      resected pancreases. RESULTS: In the 12 IDAP cases, roughly 2 cell populations,
      SD/CIS-type cells and invasive component-type cells, were detected cytologically.
      The former composed a small portion of the tumor cells, exhibited a small nuclei
      without anisonucleosis and had a decreased total quantity of chromatin as
      compared with invasive component-type cells. SD/CIS-type cells were found in
      small papillary-cohesive and compactly packed clusters and had clearly defined
      cytoplasmic borders, a nucleus individually enveloped in well-preserved cytoplasm
      and small amount of cytoplasm (< 15 microm in short diameter) without prominent
      anisocytosis. The latter comprised mostly of the tumor cells, were present
      characteristically as a loose and discohesive population and contained a
      combination of hyperchromatin, large nuclei (> 15 microm) and abundant cytoplasm
      (>21 microm). Histologically, these 12 cases exhibited IDAP with SD/CIS. Hence,
      the invasive component-type cells appeared to originate with ordinary invasive
      spread of IDAP, and the SD/CIS type cells appeared to originate with noninvasive
      intraductal spread. CONCLUSION: Two cytologic patterns originating with SD/CIS
      and invasive components of IDAP could be differentiated.

PMID- 16450901
TI  - Diagnostic utility of GLUT-1 expression in the cytologic evaluation of serous
      fluids.
AB  - OBJECTIVE: To evaluate the extent to which adenocarcinomas in body cavity fluids
      express GLUT-1 in comparison to currently available markers for adenocarcinomas.
      STUDY DESIGN: Archival paraffin-embedded cell blocks of serous fluids from 25
      cases of benign effusions containing reactive mesothelial cells and 39 cases of
      malignant effusions with metastatic adenocarcinoma (11 ovarian, 11 pulmonary, 9
      gastrointestinal and 8 breast) were retrieved from the surgical pathology files.
      All cases were stained with antibodies for GLUT-1, Ber-Ep4, B72.3 and CEA.
      Positive staining was defined as distinct linear membrane staining for GLUT-1 and
      Ber-EP4, cytoplasmic staining for CEA, and cytoplasmic or membrane staining for
      B72.3. Strong staining in at least 10% of the tumor cells was required in order
      to consider the case positive for the particular marker. RESULTS: GLUT-1 was
      expressed in 72% (28 of 39) of cases of malignant effusions: 100% (11 of 11) from
      the ovary, 91% (10 of 11) from the lung, 67% (6 of 9) from the gastrointestinal
      tract and 12% (1 of 8) from the breast. None (0 of 25) of the benign effusions
      expressed GLUT-1. Malignant effusions expressed CEA in 74% (29 of 39), Ber-Ep4 in
      85% (33 of 39), and B72.3 in 62% (24 of 39). Benign effusions expressed CEA in 3
      cases and B72.3 in 2 cases. CONCLUSION: GLUT-1 is a useful marker that can be
      applied to cytologic specimens. It can be used as a reliable component of an
      antibody panel to distinguish reactive mesothelial cells from metastatic
      adenocarcinoma in particular adenocarcinomas of body cavity effusions, in
      particular adenocarcinomas of ovarian and pulmonary origin.

PMID- 16450902
TI  - Morphology of healthy human parathyroid glands in cytologic smears.
AB  - OBJECTIVE: To compare the morphology of different parenchymal cell types in
      healthy human parathyroid glands (HPGs) in cytologic smears with their structure
      on histologic sections and to establish criteria for their recognition in smears.
      STUDY DESIGN: The HPGs of 47 subjects (27 females and 20 males) were incidentally
      removed during surgery on the thyroid gland. The tissue of glands with a normal
      macroscopic and microscopic appearance was analyzed in cytologic smears and on
      histologic sections. RESULTS: In cytologic smears (as well on histologic
      sections), dark and light chief cells predominated. Dark chief cells, which were
      more numerous than light ones, had a smaller nucleus without a visible nucleolus.
      The nucleus of light chief cells was larger with 1 or 2 nucleoli visible. The
      cytoplasm of both types of chief cells was poorly defined, grey-blue and often
      vacuolated. In the smears, the cytoplasm of oxyphilic cells was dense, gray-rose
      and well defined. In dark oxyphilic cells, the nuclei were smaller and without a
      visible nucleolus. Light oxyphilic cells had a larger nucleus and visible
      nucleolus. CONCLUSION: The identification and distribution of 4 parenchymal cell
      subtypes in the smears of pathologically altered HPGs may yield insights into the
      possible role of these cells in a specific disease.

PMID- 16450903
TI  - Prevalence of bacterial vaginosis in a community setting and role of the pap
      smear in its detection.
AB  - OBJECTIVE: To study the revalence of bacterial vaginosis (BV) in symptomatic and
      asymptomatic women in a community setting, to assess the validiy of the Pap smear
      in the detection of BV and to determine the sensitivity and specificity of
      clinical criteria for the diagnosis of BV. STUDY DESIGN: Gram staining was
      performed on vaginal secretions collected from 301 women to determine the
      prevalence of BV. Each smear was assigned a score on the basis of the bacterial
      morphotypes identified. The bacterial pattern was also studied on 270 adequate,
      Pap-stained cervical smears and compared with the gold standard, the morphotypes
      on gram stain, to derive the validity of the Pap smear in diagnosing BV. Also
      each clinical criterion defined for diagnosis of BV was independently evaluated
      to determine their sensitivity and specificity. RESULTS: The overall prevalence
      of BV was 41.5% in the study subjects using Amsel's and Nugent's criteria. The
      Pap smear was 78.3% sensitive and 86.9% specific in detection of BV. Among the
      clinical criteria, the presence of clue cells on wet mounts was both highly
      sensitive (76.7%) and specific (92.4%) for diagnosing BV, while a positive whiff
      test had a specificity of 86.9% with sensitivity of 33.9%. Vaginal pH > 4.5 was
      sensitive (88.3%) but less specific (58.6%). The presence of a thin, homogeneous
      discharge clinging to vaginal mucosa had low sensitivity (56.3%) and specificity
      (48.9%). In this study, BV was prevalent in both symptomatic and asymptomatic
      women. The routine Pap smear was able to detect BV in the majority of women. Its
      utility can be greater in asymptomatic women, in whom this infection may go
      undetected otherwise, resulting in future complications related to reproductive
      health. Among Amsel's clinical criteria, the most sensitive and specific was the
      presence of clue cells in wet mounts. They can be detected easily by laboratory
      staff with little training in primary health care seting

PMID- 16450905
TI  - Aspiration cytology of fibrosarcomatous variant of dermatofibrosarcoma
      protuberans with osteoclastlike giant cells in the chest wall: a case report.
AB  - BACKGROUND: A case of fibrosarcomatous variant of dermatofibrosarcoma protuberans
      (FS-DFSP) with osteoclastlike giant cells involved the dermis and subcutaneous
      tissue of the chest wall. This case was misdiagnosed as primary breast tumor
      clinically and had cytologic features similar to those of the metaplastic breast
      carcinoma (MRBC). CASE: A 53-year-old female presented with a nodular breast mass
      enlarging slowly over a long period of time and growing rapidly for about 3
      months. The aspirates showed high cellularity with both individually scattered
      and fascicular arrays of spindle cells. A few multinucleated giant cells without
      nuclear atypia were intermixed with dissociated spindle cells. There was no
      epithelial component in the smear. Cytologic evaluation suggested the possibility
      of a low grade spindle cell sarcoma as well as MBC. Subsequently, the patient
      underwent modified radical mastectomy, and the diagnosis of FS-DFSP was made.
      CONCLUSION: Distinguishing FS-DFSP with osteoclastlike giant cells from other
      spindle cell tumors of the breast, especially MBC showing predominantly spindle
      cell components, may pose significant challenges to the pathologist. However,
      clinical and radiologic findings and a meticulous search for other components
      raised the possibility of FS-DFSP on aspiration cytology.

PMID- 16450904
TI  - 100% rapid rescreening for quality assurance in a quality control program in a
      public health cytologic laboratory.
AB  - OBJECTIVE: To verij5 the efficacy of the quality control (QC) program in a
      cytologic laboratwy with a rapid rescreening (RR) protocol. STUDY DESIGN: RR,
      according to the Turret RR method, of all samples initially screened as negative
      at the Laboratory of Cytology, Adolfo Lutz Institute, was performed. The slides
      were reviewed for 60 seconds. Suspect smears were fully checked by 2 reviewers to
      determine the final diagnoses. A total of 2954 sequential cytologic results were
      considered in this study. Of the 2954, 2568 (86.9%) were considered initially
      negative according to our internal QC, and these cases underwent RR. Also, 10%
      were randomly selected from these negative cases for full reviewing. The internal
      QC in our laboratory includes review of cases selected according to clinical and
      cytomorphologic criteria. RESULTS: Among the 2954 total cases, QC detected 386
      (13%) atypias with final diagnoses reported according to The Bethesda System 2001
      as follows: 82 (2.18%) low grade squamous intraepithelial lesions (LSILs), 35
      (1.18%) high grade squamous intraepithelial lesions (HSILs), 2 (0.06%) squamous
      cell carcinomas, 105 (3.5%) atypical cells of undetermined significance (ASC-US),
      4 (0.12%) atypical endocervical cells (AECs) and 158 (5.3%) unsatisfactory
      samples. RR of 2568 smears initially considered negative selected 194 (7.5%)
      slides. Of the 194, 146 (75.3%) were negative, 28 (14.4%) ASC-US, 5 (2.6%) AEC, 1
      (0.5%) LSIL and 14 (7.2%) unsatisfactory. Full review of a 10% random fraction of
      the 2568 cases interpreted as negative did not detect lesions but did detect 5
      (1.95%) unsatisfactory samples. CONCLUSION: Internal QC used in our laboratory
      based on clinical and cytomorphologic criteria to select cases for review proved
      to be an efficient method of detecting HSIL and cervical cancer. The consensus
      basis of this program strongly limits the false positive and false negative rates
      and also provides subjects with continuing education. One hundred percent RR is
      more efficient than 10% full reviewing in detecting cervical abnormalities.

PMID- 16450906
TI  - Concurrent chronic myelogenous leukemia and tuberculous lymphadenitis: a case
      report.
AB  - BACKGROUND: Double pathology is uncommon. The diagnostic effort must be directed
      toward uncovering a disorder that can explain all the findings in a given
      patient. However, exceptions occur, notably in the sphere of infectious
      disorders. This is particularly true in the context of multiple infections in
      immunocompromised patients. CASE: Fine needle aspiration was performed on 2 lymph
      nodes in a 22-year-old male. Extramedullary hematopoiesis was seen in 1, while
      the other showed acellular necrosis with acid-fast bacilli. The hematologic
      workup revealed chronic myelogenous leukemia. CONCLUSION: Extramedullary
      hematopoiesis can be a cytologic clue to hematologic disorders. A search for an
      additional infectious disease may be in order.

PMID- 16450907
TI  - Fine needle aspiration cytology of focal myositis: a case report.
AB  - BACKGROUND: Focal myositis is an unusual inflammatwy lesion of the skeletal
      muscle first described by Heffizer. It is a benign condition and usually involves
      the muscles of the limbs. CASE: A man presented with a palpable mass in the left
      leg of 6 months' duration. Nuclear magnetic resonance of the leg showed a mass in
      the tibial muscle; the presumptive diagnosis was sarcoma of the muscle. Smears
      showed inflammatory cells, skeletal muscle fibers with degenerative and
      regenerative changes, and fibrous tissue, suggesting a diagnosis of focal
      myositis. An incisional muscle biopsy was performed, confirming the diagnosis.
      CONCLUSION: Focal myositis should always he considered when aspirating muscle
      masses because it is a clinical mimic of a neoplasm. The prognosis is good, and
      all cases reported in the literature were self-limiting and gradually resolved.

PMID- 16450908
TI  - Leiomyosarcoma of the breast: report of a case with fine needle aspiration
      cytologic, histologic and immunohistochemical features.
AB  - BACKGROUND: Leiomyosarcoma of the breast is a rare neoplasm. We present a case of
      primary leiomyosarcoma of the breast in a middle-aged female in whom fine needle
      aspiration cytologic features suggested sarcoma. CASE: A 55-year-old female
      presented with a rapidly growing breast lump of 1 month's duration. On
      examination, an ulcerating, 12 x 10 cm tumor was seen involving the lower medial
      and lateral quadrants of the right breast. Fine needle aspiration cytology showed
      variably sized, dissociated and loosely clustered polygonal, plump and spindle
      cells with pale blue cytoplasm and vesicular nuclei that were round, oval or
      irregular. Occasional giant forms and nucleolated and mitotic cells were present.
      A single cluster of benign ductal cells was seen. The tumor cells did not express
      immunocytologic reactivity to estrogen receptor protein. A cytologic diagnosis of
      sarcoma was given with differential diagnoses of metaplastic carcinoma and
      malignant phyllodes tumor. Histologic study established the diagnosis of
      leiomyosarcoma. Leiomyosarcoma of the breast shows fine needle aspiration
      cytologic features of sarcoma, but specific tumor typing may not be possible,
      especially when the cytologic material is inadequate for ancillary staining
      required to distinguish leiomyosarcoma from metaplastic carcinoma and malignant
      phyllodes tumor.

PMID- 16450909
TI  - Primary non-Hodgkin's lymphoma of the breast: a case report.
AB  - Extranodal non-Hodgkin's lymphoma (NHL) of the breast is a rare entity. It
      represents 0.04-1.1% of malignant tumors of the breast. 1.7-2.2% of extranodal
      lymphomas and 0.7% of all NHL. However, primary NHL (PNHL) is the most frequent
      hematopojetic tumor of the breast. CASE: A 23-year-old woman presented with a
      mass in the left breast for 3 months followed by enlarged left axillary lymph
      nodes. Mammography showed a diffuse increase in the density of the left breast.
      Other investigations were unremarkable. Both fine needle aspiration cytology
      (FNAC) and histopathology were diagnostic of NHL. Immunohistochemistry was
      confirmatory of NHL, diffuse large cell type, of B-cell lineage. CONCLUSION:
      Primary and secondary lymphomas of the breast, though rare, should be considered
      in the differential diagnosis of breast malignancies. PNHL of the breast is
      usually right sided, but this patient had left breast involvement. Diagnosis by
      FNAC was successful as the cytologic picture is similar to that of any other
      lymphoid or extranodal NHL. When histopathology and immunohistopathology are
      conclusive, FNAC, supplemented by immunocytochemistry, can be applied as a
      simple, reliable and cost-effective tool in the early diagnosis of breast
      lymphomas.

PMID- 16450910
TI  - Fine needle aspiration of subcutaneous masses caused by Aspergillus: a report of
      2 cases.
AB  - BACKGROUND: Fine needle aspiration biopsy is a well-established method for
      dijfrrentiation of infective from neoplastic lesions. Varions infective agents,
      such as mycobacteria, leishmaniasis and microfaria can be diagnosed from
      aspirates, but there are few case reports on fungal infections in aspirates.
      Cytologic diagnosis of Aspergillus has occasionally occurred on sputum, pulmonary
      samples, vaginal secretions, endometrial washings and maxillary sinus specimens.
      One case of hepatic and subcutaneous masses was diagnosed as Aspergillus by fine
      needle aspiration and confirmed by culture and histology. CASES: Two cases of
      subcutaneous aspergillosis were diagnosed by fine needle aspiration and confirmed
      by culture and histology. CONCLUSION: Fine needle aspiration cytology is a rapid,
      sensitive and important method of diagnosing Aspergillus and provides a rapid
      diagnosis, which may be life saving in an immunocompromised patient.

PMID- 16450911
TI  - Aspiration cytology of mediastinal seminoma: report of a case with emphasis on
      the diagnostic role of aspiration cytology, cell block and immunocytochemistry.
AB  - BACKGROUND: Medigstinal seminoma ia an uncommon tumor that occurs primarily in
      young males. We present a case of mediastinal seminoma in an elderly male
      diagnosed on fine needle aspiration (FNA) tytology. CASE: A 62-year-old male was
      admitted to our hospital because of anterior chest pain for 2 weeks. Chest
      computed tomography revealed a huge, lobulated mass in the anterior mediastinum.
      Aspirate smears were highly cellular. The tumor cells appeared singly or in loose
      groups of a few cells in a markedly necrotic background without lymphocytic or
      tigroid characteristics. Well-preserved cells were relatively uniform, large and
      polygonal, with round or ovoid nuclei, 2 1 prominent nucleoli and a mild to
      moderate amount of clear, occasionally vacuolated cytoplasm. The chromatin
      wasfinely granular. Mitotic figures were frequently found. The cell block section
      showed solid nests of tumor cells with cytologic features similar to those in the
      smears, supported by loose, fibrous stroma infiltrated by some lymphocytes.
      Immunocytochemically the tumor showed diffuse reactivity for c-kit and
      appearedfocally positive for placentalike alkaline phosphatase and was uniformly
      negative for pancytokeratin, CAM 5.2 low-molecular-weight cytokeratin, CD5, CD30,
      alpha-fetoprotein and leukocyte common antigen. CONCLUSION: A confident diagnosis
      of mediastinal seminoma can be established by FNA cytology, cell block and
      immunocytochemistry.

PMID- 16450912
TI  - Primary pleuropulmonary synovial sarcoma diagnosed by fine needle aspiration with
      cytogenetic confirmation: a case report.
AB  - BACKGROUND: Pleuropulmonary synovial sarcomas (PPSSs) are rare neoplasins that
      have been well described in recent years, although there are only very infrequent
      reports within the cytology literature. Such lesions present a diagnostic
      challenge on fine needle aspiration (ENA) due to several factors, particularly
      when the aspirate material displays monophasic, small cell or poorly
      differentiated morphology. Immunoperoxidase studies on cell block material and
      confirmation with molecular cytogenetics are important tools to establish the
      diagnosis and determine appropriate therapy. We report a case of PPSS in a 27
      year-old man diagnosed by computed tomography (CT)-guided FNA with confirmation
      by conventional and molecular cytogenetics. CASE: A 27-year-old man presented
      with several rapidly enlarging, pleura-based masses following a several-month
      history of recurrent hemopneumothorax. Previous surgical pathology on
      decorticated pleura was interpreted as a reactive mesothelial proliferation at
      another institution. Upon referral, CT-guided transthoracic FNA was performed.
      Smears revealed a highly cellular, dispersed "small round blue cell" neoplasm in
      a hemorrhagic background. The cytomorphology, in conjunction with a select
      immunoperoxidase panel, was diagnostic of PPSS. Conventional and molecular
      cytogenetics subsequently provided confirmation of the diagnosis. CONCLUSION:
      PPSSs are uncommon neoplasms seldom diagnosed by FNA, with only very rare reports
      in the cytology literature. Although their cytomorphology has been well
      described, monophasic tumors and other morphologic variants present a diagnostic
      challenge and may be difficult to discern from a variety of neoplastic and
      reactive/reparative processes. Emphasis should be placed upon securing material
      at the time of aspiration for immunoperoxidase studies (cell block or core
      biopsy). In equivocal cases, conventional and/or molecular cytogenetic studies
      may be needed.

PMID- 16450913
TI  - Cytologic features of high grade squamous intraepithelial lesions involving
      endocervical glands on thin-layer cytology.

PMID- 16450914
TI  - Bilateral carotid body tumor diagnosed on cytology.

PMID- 16450915
TI  - Emperipolesis in pleural mesothelial cells in a patient with chronic lymphocytic
      leukemia.

PMID- 16450916
TI  - Quality control in cervical cancer screening: Brazilian experience.

PMID- 16450917
TI  - New cytologic features of solid and papillary epithelial neoplasms of the
      pancreas.

PMID- 16450918
TI  - Yolk sac tumor of childhood: diagnosis on fine needle aspiration biopsy.

PMID- 16450920
TI  - The viability of speech-in-noise audiometric screening using domestic audio
      equipment.
AB  - Speech-in-noise audiometry has potential application as a low-cost, self
      screening test for sensorineural hearing loss. To realize this potential, the
      influence of variations in audio equipment and listening environment need
      assessment. The present study assessed: 1) the frequency response and distortion
      produced by a wide range of commercially available audio equipment; 2) the
      effects of such variations upon test results with normally hearing subjects using
      a simple, open-set, word-identification test; 3) the effect of distortion on the
      speech reception threshold using digitally applied distortion; and 4) the
      reliability of the test in listening environments with different levels of
      reverberation. In addition, preliminary tests were conducted with elderly
      listeners. The results indicate that variations in equipment have negligible
      effects on speech-in-noise audiometry. The only factor that substantially
      elevated normally hearing listeners' thresholds was high levels of room
      reverberation when using loudspeaker presentation. Variations in equipment and
      environment thus present no significant obstacle to the development of a self
      administered audiometric screening test based on speech in noise.

PMID- 16450919
TI  - The effect of auditory experience on speech perception, localization, and
      functional performance of children who use a cochlear implant and a hearing aid
      in opposite ears.
AB  - This study was aimed at determining the effect of auditory experience on binaural
      benefits from using a cochlear implant and a hearing aid in opposite ears.
      Eighteen children were evaluated using tests of speech perception, horizontal
      localization, and functional performance when they used either a cochlear implant
      alone (CI) or a cochlear implant with a hearing aid (CIHA). Eight were
      experienced CIHA users, whereas ten had not worn a hearing aid in the non
      implanted ear for up to eight years prior to participation. All children were
      fitted with a hearing aid in the non-implanted ear using the NAL-RP prescription,
      and the hearing aids were fine-tuned individually using a paired-comparisons
      procedure and a loudness balancing test. Evaluation results indicated that
      performance for all measures was significantly better with CIHA than with CI for
      both groups of children. We conclude that children who receive a unilateral
      cochlear implant should be encouraged to wear a hearing aid in the opposite ear
      where there is usable residual hearing.

PMID- 16450921
TI  - The influence of visual feedback on closed-set word test performance over time.
AB  - Closed-set word tests can be implemented with or without trial-by-trial visual
      feedback. Feedback is considered to increase subject motivation yet its influence
      on performance is unknown. The aim of this study was to compare performance on
      the Four Alternative Auditory Feature (FAAF) test with and without visual
      feedback over a 24-week period following fitting of a hearing aid. A total of 32
      elderly subjects were recruited as new users and fitted monaurally with the same
      model of linear, programmable hearing aid that provided in excess of 20 dB
      insertion gain at 2-4 kHz. Half of the subjects were provided with visual
      feedback. In these subjects, mean performance increased by 5% across the study
      period. The improvement in performance over time was statistically significant on
      analysis of variance (p < 0.05). Mean performance did not increase in the
      remaining subjects who were not provided with feedback. If closed-set word tests
      are to be used with visual feedback to measure changes over time, the potentially
      confounding effects of practice must be controlled carefully. Alternatively,
      omitting feedback leads to simpler experimental designs.

PMID- 16450922
TI  - Psychological general well-being (quality of life) in patients with cochlear
      implants: importance of social environment and age.
AB  - The purpose of this study was to investigate the variables that affect
      psychological general well-being (quality of life) in patients with cochlear
      implants (CIs). The study sample consists of 96 adult patients with a CI, aged 24
      86 years (Mean = 61.8 yrs; SD = 15.3 yrs). 48 were patients from the Sahlgrenska
      University Hospital in Sweden and 48 were patients from the University of
      Florida, USA. The Psychological General Well-being Index and the International
      Outcome Inventory-Cochlear implants were used in collecting data. Possible
      independent variables were socioeconomic factors such as age, gender,
      nationality, living arrangement, education, and social support; as well as length
      of time since implantation, age when hearing loss became a problem, and
      subjective benefit of the CI. A stepwise multiple regression analysis showed that
      49% of the variance was explained by attitudes from others, restricted social
      participation, perceived social support and age.

PMID- 16450923
TI  - Readiness of paediatric audiology services for newborn hearing screening:
      findings and implications from the programme in England.
AB  - As well as evaluating the newborn hearing screen itself, the government-funded
      evaluation of the implementation of a Newborn Hearing Screening Programme (NHSP)
      in England is assessing the impact of the screen on follow-up services. In the UK
      context, these are principally paediatric audiology, education, and social
      services. This article presents results from a mixed method research study
      involving paediatric audiology services specifically. Results demonstrate
      significant variety in current practice with regard to routine tests and
      procedures, considerable variability in number of current referrals and time
      allocated to caseloads, and considerable variability in expectations of how the
      numbers will change following newborn screening implementation. The challenges of
      and opportunities afforded by NHSP which were identified by respondents,
      highlight the urgent need for further training. The study has implications for
      paediatric audiology services that are yet to start NHSP in the UK, as well as
      for services and professionals in other countries.

PMID- 16450925
TI  - An elephant in the room.

PMID- 16450924
TI  - Methodology for quantifying perceptual effects from noise suppression systems.
AB  - Methodology is proposed for perceptual assessment of both subjective sound
      quality and speech recognition in such way that results can be compared between
      these two aspects. Validation is performed with a noise suppression system
      applied to hearing instruments. A method termed Interpolated Paired Comparison
      Rating (IPCR) was developed for time efficient assessment of subjective
      impression of different aspects of sound quality for a variety of noise
      conditions. The method is based on paired comparisons between processed and
      unprocessed stimuli, and the results are expressed as the difference in signal-to
      noise ratio (dB) between these that give equal subjective impression. For tests
      of speech recognition in noise, validated adaptive test methods can be used that
      give results in terms of speech-to-noise ratio. The methodology was shown to be
      sensitive enough to detect significant mean differences between processed and
      unprocessed speech in noise, both regarding subjective sound quality and speech
      recognition ability in groups consisting of 30 subjects. An effect on sound
      quality from the noise suppression equivalent to about 3-4 dB is required to be
      statistically significant for a single subject. A corresponding effect of 3-6 dB
      is required for speech recognition (one-sided test). The magnitude of difference
      that occurred in the present study for sound quality was sufficient to show
      significant differences for sound quality within individuals, but this was not
      the case for speech recognition.

PMID- 16450926
TI  - A collaborative rehabilitation approach to the improvement of inpatient treatment
      for persons with a psychiatric disability.
AB  - With the growth of community support programs the role of the state psychiatric
      hospital has changed. Reduced funding levels have resulted in overcrowding,
      inadequate staffing and ineffective programming. In order to improve the quality
      of care and introduce more psychiatric rehabilitation-oriented activities into
      hospital programming, a large state hospital and a state health sciences
      university have entered into a time-limited collaborative partnership. This paper
      describes that partnership and its attempt to improve staff competencies, enhance
      service delivery and integrate a more rehabilitation-oriented philosophy of care
      into the hospital through undergraduate education, in-service training, program
      development, staff mentoring and organizational change activities.

PMID- 16450927
TI  - Small business employers' views on hiring individuals with mental illness.
AB  - This study investigated the beliefs of small business employers regarding hiring
      individuals with mental illness. Fifty-eight participants completed mail-in
      questionnaires concerning beliefs and willingness to hire persons with mental
      illness. Employers were most concerned regarding the social and emotional skills
      of individuals with mental illness. Those employers who reported positive
      beliefs, had positive interactions with individuals with mental illness, or
      operated in public/social services, stated greater willingness to hire a person
      with mental illness. Methods to decrease stigma are discussed.

PMID- 16450928
TI  - The Kansas Consumer as Provider program: measuring the effects of a supported
      education initiative.
AB  - Consumers providing direct services at mental health centers contribute positive
      qualities to the service delivery system; however, there are few instructional
      programs to prepare consumers for these roles. Of the few consumer-provider
      training programs that exist, those conducting research have focused on
      employment and hospitalization outcomes. No program has researched changes in
      students' perceptions of subjective well-being. Research with students in the
      Kansas Consumer as Provider (CAP) training program found significant differences
      in students' perception of hope, self-esteem, and recovery after the training
      program.

PMID- 16450929
TI  - Facilitating discharge in state psychiatric institutions: a group intervention
      strategy.
AB  - Despite more than 30 years of deinstitutionalization, a significant number of
      individuals continue to experience prolonged stays in state psychiatric
      hospitals. Many of these individuals appear to develop an ambivalence or
      resistance to discharge. This can itself contribute to further delay in discharge
      planning and implementation. We will describe a group intervention for persons
      with long stays labeled as "resistant." This effort was guided by the premise
      that each individual could benefit from personally exploring those aspects of his
      or her experience that may be contributing to continued hospitalization. The
      group utilized standard methods of rehabilitation and training with strong
      emphasis on validating individual needs and feelings, peer support and practical
      results. After 1 1/2 years of group intervention, 5 of the 7 group members had
      achieved discharge and initial community success.

PMID- 16450930
TI  - Adjustment to community residential settings over time among older adults with
      serious mental illnesses.
AB  - This exploratory cross-sectional study examined adjustment over time of three
      groups of seniors with serious mental illnesses (N=33), who were transferred from
      a psychiatric hospital to a community residential facility from 1995-1998. The
      study participants had lived in the community for 6-41 months. Outcomes included
      measures of global, social, cognitive and ADL functioning, quality of life and
      rehospitalizations. Analyses revealed no significant deterioration in
      symptomatology, cognitive and ADL functioning between groups and a significant
      change in social functioning. Five participants were readmitted for short
      hospitalizations. Participants in all groups expressed a positive quality of life
      in their current community residence.

PMID- 16450931
TI  - What's in a service? Consumers' views of Australian mental health services.
AB  - This paper reports on a series of interviews with consumers of mental health
      services, conducted as part of the Consumer Evaluation of Mental Health Services
      project (CEO-MHS). With one of our overarching aims being to develop a consumer
      oriented and consumer directed method of evaluating mental health services, we
      considered seeking consumers' views of mental health services, using qualitative
      interviews, to be essential. Consumer Researchers from the team conducted 33
      interviews in NSW, Australia. Eleven themes emerged from analysis of the
      interview data and these themes are described in detail.

PMID- 16450932
TI  - The personal and vocational impact of training and employing people with
      psychiatric disabilities as providers.
AB  - OBJECTIVE: This study examined the feasibility of a structured peer provider
      training program and its effect on peer providers with respect to their own
      personal and vocational recovery. METHODS: Sixty-six individuals participated in
      an evaluation of a 60-hour, 5-week long peer training program. Participants were
      assessed prior to and after the training on scales to measure recovery,
      empowerment and self-concept. Analyses of variance were used to examine
      subjective changes in these measures. Job acquisition and retention data were
      also examined at posttest. RESULTS: Participants experienced gains in perceived
      empowerment, attitudes toward recovery and self-concept. Trainees went on to
      obtain peer provider positions within the mental health agency in which they
      received the training and 89% of those trained retained employment at 12 months.
      Twenty-nine percent of the initial jobs into which the peer providers were placed
      were full-time; 52% were part-time and 19% were hourly. CONCLUSIONS: Findings
      suggest that a standardized program designed to provide peer training was used
      successfully and participants' recovery and employability were improved. Further
      studies are recommended to rigorously test peer providers' impact on their
      clients and to examine the advantages that accrue to the agency when mental
      health recipients are employed as peer providers.

PMID- 16450933
TI  - Impact of a clinical-administrative review procedure on reducing reliance on
      psychotropic PRN medication.
AB  - The author reviews and evaluates the impact of a clinical/administrative review
      procedure, previously demonstrated as useful for reducing seclusion/restraint
      reliance, on psychotropic PRN reliance within a public psychiatric hospital
      (average census=310; 215 with a stay of greater than 30 days). After 20 weeks of
      baseline, the impact of the review procedure on PRN reliance was evaluated over
      an additional 52 weeks. This review procedure reduced the number of individuals
      who exceeded a review threshold from 20.8 per week prior to initiation to 12.4
      per week after initiation, a reduction of 40%. The results underscore the
      importance of clinical/administrative behavior for encouraging alternatives to
      psychotropic PRN reliance in behavior management.

PMID- 16450934
TI  - Which factors predict case management services and how do these services relate
      to client outcomes?
AB  - The current study explores two issues: which factors predict case management
      services and which case management services predict outcomes. Thirty individuals
      with schizophrenia participated in the study. Information regarding clients'
      characteristics and the working alliance was collected within the first 2 months
      of participation in the program and again 1 year later. Case managers completed a
      daily contact log for each client over the course of the year. Results suggest
      that the working alliance is a strong predictor of case management services. The
      working alliance and the frequency with which housing and medication were
      discussed were strong predictors of community functioning outcomes. Directions
      for future research are provided that are based upon these preliminary findings.

PMID- 16450935
TI  - Turning the tables: inpatients as decision makers in the treatment mall program
      at a state hospital.
AB  - Professionals have traditionally accomplished rehabilitative program development
      at public inpatient psychiatric facilities with limited input from program users.
      This report describes initial results and observations associated with the
      introduction of a user-controlled decision-making council built into the program
      development design of an evolving treatment mall at a state facility. Participant
      productivity and the satisfaction expressed by participants with regards to this
      approach captured the attention of staff facilitators and clinical managers,
      providing a sound basis for future impact studies.

PMID- 16450936
TI  - Recovery commentary: with the passage of time.

PMID- 16450937
TI  - [Importance of vaccination chronic hepatitis B].
AB  - Weak therapeutic responses and weak immune cytotoxic CD8 and CD4 response in
      chronic hepatitis B emphasize the necessity to find new therapeutic strategies
      especially as specific immunotherapy. Vaccination, whose principle was to widen
      immune repertoire, was used as a curative treatment of chronic hepatitis B. It
      would be the therapeutic procedure with the lowest cost and the potentially
      greatest benefit. Our purpose was to enhance the interest of therapeutic
      vaccination in chronic hepatitis B in order to debate later its usefulness in
      developing countries.

PMID- 16450938
TI  - [Chemotherapy in advanced non small cell lung cancer].
AB  - Lung cancer is the world's first cause of death by cancer. Locally advanced and
      metastatic non small cell cancers represent 2/3rd of cases at diagnosis and are
      of worst prognosis. We conducted a retrospective study of 202 patients to
      investigate the effect of chemotherapy on survival and quality of life. 95
      patients received chemotherapy with VP16-CDDP (88%) or Gemcitabin-CDDP.
      Improvement survival was observed in the chemotherapy group: 8 month IC 95% [6.6
      9.3] 4 month IC 95% [3.1-4.9] in the control group. Chemotherapy also had a good
      perfect on the quality of life with improvement of performance status, symptoms
      and need of analgesic. However although significant, the role of chemotherapy in
      NSCLC remains modest and new therapeutic approaches are needed including
      prevention and early detection which are probably more effective and cheaper.

PMID- 16450939
TI  - [Behaviours and needs for health of secondary-school-adolescents in Sousse
      (Tunisia)].
AB  - It was a descriptive study bearing on a probabilistic sample of one-degree
      cluster composed of 685 adolescents studying in six secondary state schools in
      Sousse, during 1998-1999 school year. The facts had been collected through an
      anonymous and self administrated questionnaire. 23.3% of youngsters had a
      negative image of themselves. Parent-adolescent communication was inexistent in
      30.6% of cases. At school, 24.3% of youngsters had a bad relationship with their
      teachers. One adolescent on four felted rather alone. One on three was not
      satisfied by leisure means putted at his disposal. Alimentary behavior was
      disturbed for one adolescent on three. The prevalence rates of smoking and
      alcoholism were respectively 14.8% and 9%. At least, one suicide attempt was
      observed in 7.7%. Among sexually active youngsters, 23.8% did not use a
      contraceptive mean. This study reveled that adolescent was threatened by a
      hostile environment which may worsen his identity crisis and exposed him to adopt
      many risky behaviors.

PMID- 16450940
TI  - [Arthritis of the hip in spondylarthorpathy: retrospective study about 126
      cases].
AB  - PURPOSE: To determine epidemiological and clinical features of arthritis of the
      hip in a Tunisian population of spondylarthrpathy (SA). PATIENTS AND METHODS:
      This is a retrospective study about patients suffering from SA treated in a
      rheumatology unit. A radiological investigation of the pelvis was systematically
      performed on each patient. RESULTS: The study in involved 126 cases of SA (83 men
      and 43 women), with a middle age of 32.6 years. Arthritis of the hip showed
      within 3.8 years. Total hip arthroplasty was indicated in 18% of cases. Arthritis
      of the hip in spondylarthropathy is an important cause of functional disability.
      We insist in our study on the frequency of arthritis of the hip in North Africa
      and particularly in patients aged under 16 years.

PMID- 16450941
TI  - [Cryptorchidism in adults. About 81 cases].
AB  - Cryptorchidism is more often diagnosed and treated in pediatric age. Its
      occurence in adult provides opportunity to study its spontaneous course. This
      study has been realized on one series of 81 files of patients cryptorchides of
      age superior than 14 years. Cryptorchidism was unilateral in 87.6% of cases and
      bilateral in 12.4% of cases. The higher the location, the more important the
      glandular atrophy and histological lesions. Global rate of secretory azoospermia
      was 93% in relation with a seminiferous disertion and an intersitial fibrosis.
      The lesions are important when cryptorchidism is bilateral. In two patients there
      was a progression to malignancy. Occasional cases of return to normal semen after
      orchidopexy have been reported, and that should preclude systematic orchidectomy
      advocated by some. Orchidopexy remain a treatment of choice even in adults.

PMID- 16450942
TI  - [Prognostic value of clinicopathologic factors in superficial bladder tumors: a
      retrospective analysis].
AB  - OBJECTIVE: To study, through a series of superficial bladder tumors, the
      prognostic factors of recurrence and tumoral progression. MATERIALS AND METHODS:
      This is a retrospective study of a series of 59 urothelial tumors of the bladder
      at stage pTa or pT1. The following parameters were considered: age, sex,
      treatment, stage and grade. The chi square test was used in search of a
      correlation between the different parameters and the course (recurrence and
      progress) of the disease. A multivariate analysis was undertaken by integrating
      factors correlated with the course. RESULTS: Thirty two tumors (54 %) had recured
      versus 27 (46%) without recurrence. Eight tumors (25 %) progressed in grade and 4
      (12,5 %) had become infiltrative. Age beyond 65 years, tumoral size > 3 cm and
      multifocality were predictive factors of recurrence with a relative risks of
      2,36, 3,28 and 3,88 respectively. In a multivariate analysis, these factors
      remained significant with adjusted relatif risks respectively of 1,36, 1,6 and
      1,7.

PMID- 16450943
TI  - [Gastrointestinal angiodysplasia: about 54 cases].
AB  - Angiodysplasia is an arteriovenous malformation which can reach the entire
      gastrointestinal tract and especially the colon. Its management is often
      difficult. The aim of this study was to assess the clinical, topographic and
      therapeutic characteristics of angiodysplasia. METHODS: it is a retrospective
      study including 54 cases of GI angiodysplasia collected over 13 years. RESULTS:
      the mean age was 62 years: 66% were males. Angiodysplastic lesions were
      predominantly located in the colon (85%). Nine patients required an endoscopic
      treatment. Electrocoagulation wases used in 8 cases and a sclerotherapy in 1
      case. Surgical resection was necessary in 2 patients which died of the after
      effects of surgery. CONCLUSION: angiodysplasia is a common etiology of chronic
      lower GI bleeding particularly in the elderly.

PMID- 16450944
TI  - [The sacrified of sacrifice day].
AB  - This prospective study was carried out in the plastic and reconstructive surgery
      department of Kassab's hospital in Tunis and the hospital of Monastir (Tunisa)
      during the sacrifice day (Aid el kebir). The study involved 50 patients. Our
      purpose was to identify the injuries of the hand occurring during this religions
      festival. The average age of patients was 39 years with sex ratio of 1.17. All
      socials and occupational sectors were affected. The lesions concern the dorsal
      face of non dominant hand (72%) with a peak in the frequency for the thumb (40%)
      and the index (37%). Extensor system of the radial finger on the non dominant
      hand was the main delicate element witch is most exposed during such festival.
      The thumb is being worthy of special mention, for it is the most serious lesions
      (amputation 10%) The lesions of flexor tendons are generally associated with
      nerve and vascular injury. 46% of patients had to undergo surgery.

PMID- 16450945
TI  - [Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 49
      Tunisian cases].
AB  - This is a retrospective study about 49 cases of xeroderma pigmentosum (XP). The
      goal was to determine the clinical features of XP in Tunisia. Our study revealed
      the predominance of a moderate form. Malignant skin tumors showed early. Squamous
      cell carcinoma (SCC) remainsed the most frequent skin malignancy in all clinical
      forms. Neurological abnormalities were more frequent in the moderate form. Mental
      retardation and peripheral neuropathy were the most common signs.

PMID- 16450946
TI  - [The approach diagnoses of ovarian tumors by echography].
AB  - In more of positive diagnosis, echography makes it possible to approach the
      histological nature of ovarian tumors. From a series of 106 cases of ovarian
      tumours, we propose to evaluate this approach by analysing the various
      echographic signs according to histological types'. The serous cysts are
      anechogen in 77,7% of the cases. The mucinous cysts are anechogen in 71,4% and
      finely echogen in 28,5% of the cases. The dermoid cysts are echogen in 47,3% and
      heterogeneous in 26,3%. The endometriosic cysts can be finely echogen (45%),
      heterogeneous (25%) or echogen (20%). The malignant tumors are of mixed aspect in
      54,55% of the cases. The sensitivity of echography for the malignant tumors is
      81,82% whereas specificity is 75,79%. The negative predictive value is 97,3%, and
      the positive predictive value is 28,13%. The size of the tumor, the vegetations
      and the partitions are also studied: a size lower than 5 cm and the absence of
      partition and vegetation are synonymous with benignity in all the cases.

PMID- 16450947
TI  - [Study of contents of nitrates, fluorides, aluminium in dialysis water in
      Tunisia].
AB  - Nitrates, fluorides and aluminum have often been incriminated in cases of
      poisoning sometimes life threatening such as methaemoglobinaemia, dental and
      skeletal fluorosis, and myoclonal encephalopathy in patients undergoing
      haemodialysis. The three elements mentioned have something in common: their water
      origin (drinking water and dialysis water). To study the situation in Tunisia in
      this respect we propose to determinate the contents of nitrates, fluorides, and
      aluminum in drinking water and dialysis water supplied by the water board
      (SONEDE). 540 samples of drinking water and dialysis water were taken from 95
      centers of haemodialysis scattered all over the country, between January 2000 and
      December 2001. These samples are divided in three parts (drinking water, soften
      water, and dialysis water ). Results show levels of fluorides < 1.5 ppm in most
      areas with the exception of zones rich in phosphate where the mean level is 1.61
      +/- 1.22. the levels of nitrates are in most regions < 50mg/l and those of
      aluminum < 100microg/l. The levels of fluorides, nitrates and aluminum in
      dialysis water were within acceptable national and international limits excepting
      a few centers where the levels of the these contaminants are high, exposing
      patients on haemodialysis to acute and chronic intoxication. This contamination
      is caused in majority of cases by a dysfunction of water dialysis treatment
      chain, therefore caution is necessary and strict measures of control should be
      introduced.

PMID- 16450948
TI  - [Appendiculoureteroplasty: about 6 cases].
AB  - OBJECTIVE: Through this work we want to specify the place of
      ureteroappendiculoplasty as an important technical procedure for ureteral
      substitution. MATERIAL AND METHODS: Between January 1997 and September 2002, 6
      patients had an appendiculoureteroplasty. RESULTS: four women and two men with a
      mean age of 37 years (range 12 to 55 years) had a lesion of the right ureter. The
      decision is use the appendix was taken peroperatively in front of the
      difficulties associated with other procedures. The mean length of ureteral loss
      was 12 cm (6-15 cm), the pelvic portion of ureter was more damaged than other
      segments (4 cases). The appendix was suspended between the 2 ureteric extremities
      in 2 cases and between the ureter and the bladder in 4 cases. After a mean follow
      up of 3 years (1-5 years), we noted a recovery of the kidney function in all
      cases. CONCLUSIONS: autotransplantation of the appendix can be considered a
      simple procedure that allows sometimes to reestablish the continuity of the
      ureter with good results.

PMID- 16450949
TI  - [Breast cancer and pregnancy: a study of 3 cases].
AB  - Cancer is rare during pregnancy. Breast cancer is the most common cancer in
      pregnant women. We report 3 cases of breast cancer associated with pregnancy. The
      mean age was of 34 years. Cancer was detected during the second trimester of
      pregnancy in two patients. They were treated with mastectomy followed by 6
      courses of adjuvant chemotherapy. The first course was given before delivery.
      Loco regional radiotherapy was given after the end of chemotherapy. The third
      patient presented with a bilateral breast cancer which was discovered 2 months
      after delivery. The patient was treated with mastectomy of the left breast and
      conservative surgery of the right one, associated with adjuvant chemotherapy and
      radiotherapy. Two patients died the course of the disease. Twenty months later,
      the third patient is still alive, free of all symptoms and signs. Based on our
      findings and through a review of literature, we try to determine the
      epidemiological and clinical features of this association as well the outcome of
      therapy and eventual prognosis.

PMID- 16450950
TI  - [Usefulness of endoscopic ultrasonography for diagnosis between multivesicular
      hydatic cyst and serous cystadenoma of the pancreas. Case report].
AB  - Hydatid cyst of the pancreas is very rare. However, it should be suspected in
      every case of pancreatic cyst, especially in hydatid countries where hydatic cyst
      disease is endemic. In the paper we report the first case of a multivesicular
      hydatid cyst of the pancreas explored by endoscopic ultrasonography. Endoscopic
      ultrasonography is very reliable in the investigation of pancreatic cystic
      tumors. However it did not allow us to define semiological criteria capable of
      permitting a differential diagnosis between a hydatid cyst and serous
      cystadenoma. Per-echoendoscopic transduodenal puncture might improve the
      efficiency of this procedure with of hydatid cysts of the head of the pancreas.

PMID- 16450951
TI  - [Lung cancer and chondromatous hamartoma: a case report].
AB  - The association lung cancer with chondromatous hamartoma is frequent. We present
      a case of synchronous primary lung adenocarcinoma and chondromatous hamartoma.
      Although hamartoma is generally considered to be a benign tumor, there have been
      several reports of increased risk of lung cancer in patients with a chondromatous
      hamartoma. Therefore we recommend that patients with hamartoma should be
      submitted to a complete evaluation and to regular follow up, considering the risk
      of associated synchronous malignancy.

PMID- 16450953
TI  - The moribund state as an experimental endpoint.

PMID- 16450954
TI  - Animal welfare and toxicology/safety studies: making sense of the regulatory
      environment.

PMID- 16450952
TI  - [Imaging diagnosis of an unilateral painful ophtalmoplegia].
AB  - The ophtalmoplegia may be due to several lesions and the diagnosis is made by
      imaging modalities. We report the case of a giant aneurysm of the wright
      intracavernous internal carotid artery revealed by painful ophtalmoplegia with
      subarachnoid haemorrhage. The diagnosis was made by magnetic resonance imaging
      and angiography.

PMID- 16450956
TI  - Analgesic efficacy of acetaminophen and buprenorphine administered in the
      drinking water of rats.

PMID- 16450955
TI  - A comparison of ketamine, ketamine-acepromazine, and tiletamine-zolazepam on
      various hematologic parameters in rhesus monkeys (Macaca mulatta).

PMID- 16450957
TI  - Synthetic cast protective dressing for skin experiments in rats.

PMID- 16450958
TI  - Breeding nine-banded armadillos (Dasypus novemcinctus) in captivity.

PMID- 16450959
TI  - Evaluation of objects for environmental enrichment of mice.

PMID- 16450960
TI  - Surgical management of a nasal adenocarcinoma in an olive baboon (Papio
      cynanocephalus).

PMID- 16450961
TI  - Multicystic lesion of the jaw in a rabbit.

PMID- 16450962
TI  - A simple technique for collection of large amounts of blood from tranquilized or
      anesthetized rabbits.

PMID- 16450963
TI  - Safety testing--an essential use of laboratory animals.

PMID- 16450964
TI  - Institutional Animal Care and Use Committees: a survey covering 10 years of
      experience.

PMID- 16450965
TI  - Barrier film protects skin of incontinent rats.

PMID- 16450966
TI  - A practical in-house method for bile duct cannulation of rats.

PMID- 16450967
TI  - Use of computed tomography to aid in diagnosing transient blindness in a rhesus
      macaque (Macaca mulatata).

PMID- 16450968
TI  - A rapid and simple technique for serial or continuous collection of blood samples
      and intravenous administration of drugs to conscious swine.

PMID- 16450969
TI  - The influence of position and orientation of racks on airflow dynamics in a small
      animal room.

PMID- 16450970
TI  - Spontaneous hypertrophic osteopathy in a Wistar rat.

PMID- 16450971
TI  - Hemangiopericytoma in a rat.

PMID- 16450972
TI  - Spontaneous carotid-cavernous sinus fistula in an aged rhesus monkey (Macaca
      mulatta).

PMID- 16450973
TI  - In-house development of an integrated management information system for a
      laboratory animal facility.

PMID- 16450974
TI  - AAALAC history through 1990.

PMID- 16450975
TI  - Correlation of inulin with creatinine clearance in partial unilateral ureteral
      obstruction for determination of differential glomerular filtration rate in
      rabbits.

PMID- 16450976
TI  - Use of the laryngeal mask airway for emergency or elective airway management
      situations in pigs.

PMID- 16450977
TI  - The use of plastinated specimens as teaching aids of orolaryngeal anatomy in
      selected laboratory animals.

PMID- 16450978
TI  - Grooming-contact bars provide social contact for individually caged laboratory
      macaques.

PMID- 16450980
TI  - Rodent enrichment devices--evaluation of preference and efficacy.

PMID- 16450979
TI  - Nutritional, physiologic, and behavioral effects of metabolism crates on lambs.

PMID- 16450981
TI  - Comparison of the effect of two automatic watering systems and environmental
      manipulations on frequency of wet bedding created by mice housed in solid-bottom
      suspended caging systems.

PMID- 16450982
TI  - An innovative aquatic non-recirculating system for use in housing African clawed
      frogs (Xenopus laevis).

PMID- 16450983
TI  - Customized rat restraint.

PMID- 16450984
TI  - Use of a modified rotating cutting needle for testicular biopsy in cynomolgus
      monkeys (Macaca fascicularis).

PMID- 16450985
TI  - U.S. primate research is alive and well in the 1990s.

PMID- 16450986
TI  - Understanding the emotional experiences of animal research personnel.

PMID- 16450987
TI  - Sampling of prenatal and postnatal offspring from individual rat dams enhances
      animal use without compromising development.

PMID- 16450988
TI  - Continuous deep intravenous infusion for use in rat pre- and postnatal studies.

PMID- 16450989
TI  - Evaluation of treatment strategies for Rauschtineria citelli (Nematoda;
      Oxyuridae; Syphacinae) infections in laboratory squirrels.

PMID- 16450991
TI  - Spontaneous osteosarcoma in a severe combined immunodeficient (SCID/Sed) mouse.

PMID- 16450990
TI  - Novel device for small animal anesthesia.

PMID- 16450992
TI  - Serous biliary cystadenoma in ferrets (Mustela putorius furo).

PMID- 16450993
TI  - Plasma cell neoplasia in a Rhesus monkey and brief review of related dysplasias
      in man and nonhuman primates.

PMID- 16450994
TI  - Colonic intussusception in a rabbit.

PMID- 16450995
TI  - Surgical correction of an aberrant right subclavian artery in a cat.

PMID- 16450996
TI  - Gold apes hydrogen. The structure and bonding in the planar B7Au2- and B7Au2
      clusters.
AB  - We produced the B7Au2- mixed cluster and studied its electronic structure and
      chemical bonding using photoelectron spectroscopy and ab initio calculations. The
      photoelectron spectra of B7Au2- were observed to be relatively simple with
      vibrational resolution, in contrast to the complicated spectra observed for pure
      B7-, which had contributions from three isomers (Alexandrova et al. J. Phys.
      Chem. A 2004, 108, 3509). Theoretical calculations show that B7Au2- possesses an
      extremely stable planar structure, identical to that of B7H2-, demonstrating that
      Au mimics H in its bonding to boron, analogous to the Au-Si bonding. The ground
      state structure of B7Au2- (B7H2-) can be viewed as adding two Au (H) atoms to the
      terminal B atoms of a higher-lying planar isomer of B7-. The bonding and
      stability in the planar B7Au2- (B7H2-) clusters are elucidated on the basis of
      the strong covalent B-Au (H) bonding and the concepts of
      aromaticity/antiaromaticity in these systems.

PMID- 16450997
TI  - Photoisomerization of cis,cis-1,4-diphenyl-1,3-butadiene in the solid state: the
      bicycle-pedal mechanism.
AB  - The cis-trans photoisomerization of crystalline or powdered cis,cis-1,4-diphenyl
      1,3-butadiene (cc-DPB) was studied at room temperature. The progress of the
      reaction was monitored by fluorescence spectroscopy, powder X-ray diffraction, 1H
      NMR and HPLC. High conversions (up to 90%) to the trans,trans isomer were
      observed in a crystal to crystal reaction. Formation of the cis,trans isomer, the
      sole product obtained in solution and in very viscous glassy media at 77 K is
      entirely suppressed in the solid state. The observed two-bond photoisomerization
      is explained by Warshel's bicycle-pedal photoisomerization mechanism (BP). The
      results are consistent with X-ray diffraction measurements, which have revealed
      that cc-DPB molecules exist in crystals in edge to face alternating arrays of two
      conformer structures whose phenyl rings deviate significantly from the plane of
      the central diene moiety ( approximately 40 degrees ). One of the conformers has
      the two phenyls in parallel planes and the other in roughly perpendicular planes.
      Least motion considerations suggest that the former should undergo the two-bond
      photoisomerization more easily, in agreement with observations that indicate that
      the reaction proceeds in discrete stages. Recently reported cis,cis- to
      trans,trans-muconate photoisomerizations in the solid state are proposed to also
      proceed via the BP mechanism. The reactions are consistent with the X-ray crystal
      structures of the cis,cis-muconate isomers.

PMID- 16450998
TI  - Hydrogen bonding properties of Coumarin 151, 500, and 35: the effect of
      substitution at the 7-amino position.
AB  - The steady-state spectral properties (absorption and emission) of three
      structurally similar Coumarin dyes, C151, C500, and C35 were investigated in 13
      different solvents. A Kamlet-Taft (KT) analysis of the spectral peak frequencies
      reveals that, in addition to polarity, hydrogen bonding between the carbonyl
      oxygen and a protic solvent in the excited state imparts maximum stabilization
      for C151 and minimum for C35, while that for C500 lies in between. The spectral
      properties of the three dyes in two solvents, chloroform and THF, which have
      similar polarity in the KT scale but have only hydrogen-bond donor (chloroform)
      and hydrogen-bond acceptor (THF) properties, are seen to be sensitive to the
      substitution pattern at the 7-amino position. In addition, a slow emission
      spectral relaxation is observed for C151 and C500 having a time constant of
      approximately 500 ps in chloroform. For C35 this was too fast to be detected by
      the time resolution of our setup. The exact reason for this slow spectral
      relaxation in chloroform is unclear at present, and further studies are needed to
      understand clearly the structural effects on the hydrogen bonding dynamics of
      these dyes.

PMID- 16450999
TI  - Solvation dynamics of the electron produced by two-photon ionization of liquid
      polyols. 1. Ethylene glycol.
AB  - Solvated electrons have been produced in ethylene glycol by two-photon ionization
      of the solvent with 263 nm femtosecond laser pulses. The two-photon absorption
      coefficient of ethylene glycol at 263 nm is determined to be beta = (2.1 +/- 0.2)
      x 10(-11) m W(-1). The dynamics of electron solvation in ethylene glycol has been
      studied by pump-probe transient absorption spectroscopy. So, time-resolved
      absorption spectra ranging from 430 to 710 nm have been measured. A blue shift of
      the spectra is observed for the first tens of picoseconds. Using the Bayesian
      data analysis method, the observed solvation dynamics are reconstructed with
      different models: stepwise mechanisms, continuous relaxation models, or
      combinations of stepwise and continuous relaxation. Comparison between models is
      in favor of continuous relaxation, which is mainly governed by solvent molecular
      motions.

PMID- 16451000
TI  - Electron-transfer oxidation properties of unsaturated fatty acids and mechanistic
      insight into lipoxygenases.
AB  - Rate constants of photoinduced electron-transfer oxidation of unsaturated fatty
      acids with a series of singlet excited states of oxidants in acetonitrile at 298
      K were examined and the resulting electron-transfer rate constants (k(et)) were
      evaluated in light of the free energy relationship of electron transfer to
      determine the one-electron oxidation potentials (E(ox)) of unsaturated fatty
      acids and the intrinsic barrier of electron transfer. The k(et) values of
      linoleic acid with a series of oxidants are the same as the corresponding k(et)
      values of methyl linoleate, linolenic acid, and arachidonic acid, leading to the
      same E(ox) value of linoleic acid, methyl linoleate, linolenic acid, and
      arachidonic acid (1.76 V vs SCE), which is significantly lower than that of oleic
      acid (2.03 V vs SCE) as indicated by the smaller k(et) values of oleic acid than
      those of other unsaturated fatty acids. The radical cation of linoleic acid
      produced in photoinduced electron transfer from linoleic acid to the singlet
      excited state of 10-methylacridinium ion as well as that of 9,10
      dicyanoanthracene was detected by laser flash photolysis experiments. The
      apparent rate constant of deprotonation of the radical cation of linoleic acid
      was determined as 8.1 x 10(3) s(-1). In the presence of oxygen, the addition of
      oxygen to the deprotonated radical produces the peroxyl radical, which has
      successfully been detected by ESR. No thermal electron transfer or proton-coupled
      electron transfer has occurred from linoleic acid to a strong one-electron
      oxidant, Ru(bpy)3(3+) (bpy = 2,2'-bipyridine) or Fe(bpy)3(3+). The present
      results on the electron-transfer and proton-transfer properties of unsaturated
      fatty acids provide valuable mechanistic insight into lipoxygenases to clarify
      the proton-coupled electron-transfer process in the catalytic function.

PMID- 16451002
TI  - Quenching mechanism of Rose Bengal triplet state involved in photosensitization
      of oxygen in ethylene glycol.
AB  - The quenching rate constants of the excited triplet state of Rose Bengal (RB) by
      oxygen (k(obs)) were measured in ethylene glycol (EG) at different temperatures
      using nanosecond laser flash photolysis. Although a plot of the quenching rate
      constant k(obs) for RB triplet state vs oxygen concentration is linear at 20
      degrees C, the oxygen dependence of k(obs) does not exhibit linearity but upward
      curvature at high temperatures from 130 to 140 degrees C. The upward curvature at
      high temperatures is not well-described by a kinetic scheme first postulated by
      Gijzeman et al., which is characterized by exciplex formation and a unimolecular
      dissociation of the exciplex to products, but instead by a more comprehensive
      mechanism involving a bimolecular dissociation in addition to a unimolecular one.
      The measurements of the oxygen dependence of k(obs) for RB triplet state at
      different temperatures yielded a reaction enthalpy for the exciplex formation of
      150 kJ mol(-1). Due to the large exothermic reaction enthalpy, equilibrium was
      obtained for the exciplex at 20 degrees C even at low oxygen concentration and
      the bimolecular quenching by oxygen became the major dissociation process. The
      equilibrium attainment and bimolecular dissociation provide a linear oxygen
      dependence of k(obs) to all outward appearances. Therefore, linearity does not
      always mean that exciplex dissociation proceeds solely through a unimolecular
      mechanism.

PMID- 16451003
TI  - Computational characterization of low-lying states and intramolecular charge
      transfers in N-phenylpyrrole and the planar-rigidized fluorazene.
AB  - Low-lying states and intramolecular charge transfers in N-phenylpyrrole (PP) and
      its planar-rigidized derivative fluorazene (FPP) have been investigated by ab
      initio methodologies. On the basis of calculations, properties of the excited
      states and plausible dual-fluorescence mechanisms have been elucidated. Present
      results show that S2 as a key state is involved in the consecutive photophysical
      processes. The S2 state is easily populated under excitation. In the polar MeCN
      solution, S2 can evolve to either a lower-energy locally excited state or a lower
      energy solvated intramolecular charge-transfer state (S-ICT). The former emits a
      normal fluorescence back to the ground state, and the latter is exclusively
      responsible for the red-shifted fluorescence band. Calculations reveal that the
      emissive ICT states in both FPP and PP have similar geometric features, an
      elongated N-phenyl bond, a pyramidal carbon atom linking the pyrrole ring, and a
      quinonoid phenyl ring. The twisting of molecule around the N-phenyl bond is not
      necessary for the intramolecular charge transfer. Predicted absorption and
      emission spectra are in reasonable agreement with the experimental observations.

PMID- 16451001
TI  - Characterizing the fluorescence intermittency and photobleaching kinetics of dye
      molecules immobilized on a glass surface.
AB  - The blinking behavior of single Atto565 molecules on a glass surface is studied
      under air or nitrogen atmospheres using confocal microscopy. The broad
      distributions for both on- and off-time durations obey power law kinetics that
      are rationalized using a charge tunneling model. In this case, a charge is
      transferred from the Atto565 molecule to localized states found on the glass
      surface. Subsequent charge recombination by back charge tunneling from trap to
      Atto565 cation (i.e., dark state) restores the fluorescence. The off-time
      distribution is independent of excitation intensity (I), whereas the on-time
      distribution exhibits a power law exponent that varies with I. Two pathways have
      been identified to lead to the formation of the radical dark state. The first
      involves direct charge tunneling from the excited singlet S1 state to charge
      traps in the surrounding matrix, and the second requires charge ejection from the
      triplet T1 state after intersystem crossing from S1. Monte Carlo simulation
      studies complement the two-pathway model. Photobleaching curves of both single
      and ensemble molecules do not exhibit monoexponential decays suggesting complex
      bleaching dynamics arising from triplet and radical states.

PMID- 16451004
TI  - Mechanism of the cyclopropenone decarbonylation reaction. A density functional
      theory and transient spectroscopy study.
AB  - The density functional theory analysis predicts that the thermal decarbonylation
      of cyclopropenones proceeds by the sequential and regioselective cleavage of both
      single bonds in a three-membered ring. The initial ring-opening process results
      in the formation of a reactive zwitterionic intermediate 6, which is separated
      from the free alkyne and carbon monoxide by a very low energy barrier.
      Femtosecond pump-probe transient absorption spectroscopy experiments showed that
      light-induced decarbonylation is also a stepwise process but apparently proceeds
      on the excited-state surface. The lifetime of the intermediate in the
      photodecarbonylation reaction is very short and is dependent on substitution and
      solvent polarity. Thus, bis-p-anisyl-substituted species decays with tau = 0.6
      ps, bis-alpha-naphthyl-substituted intermediate has a lifetime of tau = 11 ps,
      while the bis(2-methoxy-1-naphthyl)-substituted analogue survives for 83 ps in
      chloroform and for 168 ps in argon-saturated methanol. The loss of carbon
      monoxide from these intermediates results in the formation of corresponding
      acetylenes in an electronically ground state. The addition of triplet quenchers
      does not affect the dynamics or outcome of the reaction.

PMID- 16451005
TI  - Excited-state hydrogen-atom transfer along solvent wires: water molecules stop
      the transfer.
AB  - Excited-state hydrogen-atom transfer (ESHAT) along a hydrogen-bonded solvent wire
      occurs for the supersonically cooled n = 3 ammonia-wire cluster attached to the
      scaffold molecule 7-hydroxyquinoline (7HQ) [Tanner, C.; et al. Science 2003, 302,
      1736]. Here, we study the analogous three-membered solvent-wire clusters
      7HQ.(NH3)n.(H2O)m, n + m = 3, using resonant two-photon ionization (R2PI) and UV
      UV hole-burning spectroscopies. Substitution of H2O for NH3 has a dramatic effect
      on the excited-state H-atom transfer: The threshold for the ESHAT reaction is
      approximately 200 cm(-1) for 7HQ.(NH3)3, approximately 350 cm(-1) for both
      isomers of the 7HQ.(NH3)2.H2O cluster, and approximately 600 cm(-1) for
      7HQ.NH3.(H2O)2 but increases to approximately 2000 cm(-1) for the pure 7HQ.(H2O)3
      water-wire cluster. To understand the effect of the chemical composition of the
      solvent wire on the H-atom transfer, the reaction profiles of the low-lying
      electronic excited states of the n = 3 pure and mixed solvent-wire clusters are
      calculated with the configuration interaction singles (CIS) method. For those
      solvent wires with an NH3 molecule at the first position, injection of the H atom
      into the wire can occur by tunneling. However, further H-atom transfer is blocked
      by a high barrier at the first (and second) H2O molecule along the solvent wire.
      H-atom transfer along the entire length of the solvent wire, leading to formation
      of the 7-ketoquinoline (7KQ) tautomer, cannot occur for any of the H2O-containing
      clusters, in agreement with experimentally observed absence of 7KQ fluorescence.

PMID- 16451006
TI  - Flexible biradicals in liquid and supercritical carbon dioxide: the exchange
      interaction, the chain dynamics, and a comparison with conventional solvents.
AB  - X-band time-resolved electron paramagnetic resonance (TREPR) spectra of three
      flexible biradicals of varying chain length and structure were obtained in liquid
      and supercritical carbon dioxide (CO2) solutions and compared to conventional
      solvents. For C16 acyl-alkyl biradical 1a, an average spin exchange interaction
      between the radical centers, J(avg), was obtained by spectral simulation using a
      simple model for spin-correlated radical pairs (SCRPs) and a small amount of T2
      relaxation from a previously established J modulation mechanism. A large solvent
      effect on J(avg) was observed for the first time, varying by almost 1 order of
      magnitude from CO2 (J(avg) = -120 +/- 10 MHz) to heavy mineral oil (-11 +/- 3
      MHz) for 1a. For C15 bis(alkyl) biradical 1b, spectra obtained under
      supercritical conditions are only slightly different from those detected in
      liquid CO2 but differ from spectra taken in benzene. For C10 acyl-alkyl biradical
      2a, more emissive spin polarization due to S-T- mixing is observed in CO2 than in
      benzene. These results are discussed in terms of solvent properties such as
      dielectric constant, viscosity, and specific interactions. Both chain dynamics
      and changes to the equilibrium distribution of end-to-end distances can alter
      J(avg) and the observed ratio of S-T0 to S-T- mixing; however, faster chain
      dynamics is concluded to be the most likely cause of the observed effects in
      these systems.

PMID- 16451007
TI  - Density matrix analysis, simulation, and measurements of electronic absorption
      and fluorescence spectra of spirobifluorenes.
AB  - The linear absorption and fluorescence spectra as well as the oscillator
      strengths of 2,2',7,7'-tetraphenyl-9,9'-spirobifluorene (A), 2,2',7,7'
      tetrakis(biphenyl-4-yl)-9,9'-spirobifluorene (B), and 2,2',7,7'-tetrakis(9,9'
      spirobifluoren-2-yl)-9,9'-spirobifluorene (C) are calculated on the basis of the
      collective electronic oscillator (CEO) approach of Mukamel et al. (see, e.g.,
      Chem. Rev. 2002, 102, 3171). The graphical visualization and quantitative
      characterization of CEO modes allows one to extract the real-space distribution
      of electronic excitations of the molecules under study. Effects of the
      lengthening and branching of the oligophenylene segments have been analyzed. The
      influence of the lowest excited (S1) vs ground-state (S0) geometry changes on the
      CEO modes is investigated and related to the geometry changes of the molecular
      parts. The obtained theoretical results are in good agreement with experimental
      trends observed in absorption and fluorescence data.

PMID- 16451008
TI  - Collision-energy-resolved penning ionization electron spectroscopy of
      phenylacetylene and diphenylacetylene by collision with He*(2(3)s) metastable
      atoms.
AB  - Penning ionization of phenylacetylene and diphenylacetylene upon collision with
      metastable He*(2(3)S) atoms was studied by collision-energy-/electron-energy
      resolved two-dimensional Penning ionization electron spectroscopy (2D-PIES). On
      the basis of the collision energy dependence of partial ionization cross-sections
      (CEDPICS) obtained from 2D-PIES as well as ab initio molecular orbital
      calculations for the approach of a metastable atom to the target molecule,
      anisotropy of interaction between the target molecule and He*(2(3)S) was
      investigated. For the calculations of interaction potential, a Li(2(2)S) atom was
      used in place of He*(2(3)S) metastable atom because of its well-known interaction
      behavior with various targets. The results indicate that attractive potentials
      localize in the pi regions of the phenyl groups as well as in the pi-conjugated
      regions of the acetylene group. Although similar attractive interactions were
      also found by the observation of CEDPICS for ionization of all pi MOs localized
      at the C[triple bond]C bond, the in-plane regions have repulsive potentials.
      Rotation of the phenyl groups about the C[triple bond]C bond can be observed for
      diphenylacetylene because of a low torsion barrier. So the examination of
      measured PIES was performed taking into consideration the change of ionization
      energies for conjugated molecular orbitals.

PMID- 16451009
TI  - Electron impact ionization of haloalkanes in helium nanodroplets.
AB  - Electron impact (EI) mass spectra of a selection of C1-C3 haloalkanes in helium
      nanodroplets have been recorded to determine if the helium solvent can
      significantly reduce molecular ion fragmentation. Haloalkanes were chosen for
      investigation because their EI mass spectra in the gas phase show extensive ion
      fragmentation. There is no evidence of any major softening effect in large helium
      droplets ( approximately 60 000 helium atoms), but some branching ratios are
      altered. In particular, channels requiring C-C bond fission or concerted
      processes leading to the ejection of hydrogen halide molecules are suppressed by
      helium solvation. Rapid cooling by the helium is not sufficient to account for
      all the differences between the helium droplet and gas phase mass spectra. It is
      also suggested that the formation of a solid "snowball" of helium around the
      molecular ion introduces a cage effect, which enhances those fragmentation
      channels that require minimal disruption to the helium cage for products to
      escape.

PMID- 16451010
TI  - Liquid structure and preferential solvation of metal ions in solvent mixtures of
      N,N-dimethylformamide and N-methylformamide.
AB  - Raman spectra of aprotic N,N-dimethylformamide (DMF) and protic N-methylformamide
      (NMF) mixtures containing manganese(II), nickel(II), and zinc(II) perchlorate
      were obtained, and the individual solvation numbers around the metal ions were
      determined over the whole range of solvent compositions. Variation profiles of
      the individual solvation numbers with solvent composition showed no significant
      difference among the metal systems examined. In all of these metal systems, no
      preferential solvation occurs in mixtures with DMF mole fraction of x(DMF) < 0.5,
      whereas DMF preferentially solvates the metal ions at x(DMF) > 0.5. The liquid
      structure of the mixtures was also studied by means of small-angle neutron
      scattering (SANS) and low-frequency Raman spectroscopy. SANS experiments
      demonstrate that DMF molecules do not appreciably self-aggregate in the mixtures
      over the whole range of solvent composition. Low-frequency Raman spectroscopy
      suggests that DMF molecules are extensively hydrogen-bonded with NMF in NMF-rich
      mixtures, whereas NMF molecules extensively self-aggregate in DMF-rich mixtures,
      although the liquid structure in neat NMF is partly ruptured. The bulk solvent
      structure in the mixtures thus varies with solvent composition, which plays a
      decisive role in developing the varying profiles of the individual solvation
      numbers of metal ions in the solvent mixtures.

PMID- 16451012
TI  - 3,4-dimethylbenzyl radical formed in a corona discharge of 1,2,4
      trimethylbenzene.
AB  - A precursor, 1,2,4-trimethylbenzene, seeded in a large amount of an inert carrier
      gas, helium, was electrically discharged in a corona-excited supersonic expansion
      using a pinhole-type glass nozzle. The blue-green colored fluorescence emanating
      from the downstream jet was recorded with a long path monochromator to observe
      the vibronic emission spectrum of the benzyl-type radical formed. Analysis of the
      spectrum suggests that the most dominant product of the corona discharge is the
      3,4-dimethylbenzyl radical formed by extracting a hydrogen atom from the methyl
      group at the 4-position. The electronic energies of the D1 and D2 states and the
      vibrational mode frequencies of the 3,4-dimethylbenzyl radical were accurately
      obtained for the first time by comparison with those from an ab initio
      calculation as well as those of the known vibrational mode frequencies of the
      precursor.

PMID- 16451011
TI  - Surface-enhanced resonance Raman scattering and density functional calculations
      of hemicyanine adsorbed on colloidal silver surface.
AB  - Resonance Raman (RR) and surface-enhanced resonance Raman scattering (SERRS) of
      4'-(N,N'-dimethylaminostyryl)-4-propylpyridinium bromide (hemicyanine, HC dye) in
      acetonitrile solution and on a colloidal silver surface have been investigated.
      The structure of the dye in the ground (S0) and excited (S1) electronic states
      was optimized using density functional calculations along with the B3LYP and the
      configuration interaction with the singlet excitation (CIS) methods,
      respectively, using the 6-31G basis set. The vibrational frequencies of the
      molecule were computed at the optimized geometry and compared with the observed
      Raman bands. A complete normal-mode analysis has been carried out because it is
      essential for the accurate assignment of the vibrational spectra. From the
      observed enhancement along various in-plane and out-of-plane vibrations in the
      SERRS spectrum and from theoretical calculations, it has been inferred that the
      interaction with the silver surface occurs via the nitrogen lone pair of the
      pyridyl or the dimethylamino group of the molecule with a tilted orientation. The
      observed red-shifts in the SERRS spectrum along various vibrations indicate
      strong interaction (chemisorption) of the HC dye with the silver surface. This is
      also supported by the presence of a Ag-N stretching vibration at 241 cm(-1). The
      effect of the dye concentration on the orientation of the molecule is also
      discussed.

PMID- 16451013
TI  - Infrared emission and theoretical study of carbon monoxide adsorbed on alumina
      supported Rh, Ir, and Pt catalysts.
AB  - The infrared emission spectra of CO adsorbed on alumina-supported 1, 3, and 5 wt
      % Rh, Ir, and Pt metal-containing catalysts were studied at 423 and 473 K. While
      CO is adsorbed in dicarbonyl (dimer), linearly (on-top) bonded and bridged
      carbonyl forms on rhodium and platinum, the dimer form is dominant on iridium.
      The relative intensity of Rh-CO and Ir-CO linear bands decrease with increasing
      temperature compared to the intensity of the dicarbonyl bands; the corresponding
      bands on Pt behave the opposite way. Two dicarbonyl and two linear Pt-CO bands
      were identified in the infrared spectra of Pt/Al(2)O(3) catalysts. The surface
      structure (kinked or planar Pt atoms), the dispersity of the metal, the
      temperature, and the quantity of adsorbed CO on the surfaces all have an effect
      on the fine structure of the Pt-CO stretching bands. The metal-carbon and CO
      stretching force constants were calculated for surface dicarbonyl, linearly
      bonded CO, and bridged carbonyl species. The metal-carbon stretching wavenumbers
      and force constants were predicted and compared between surface species and metal
      carbonyl complexes. The iridium-carbon bonds were found always stronger than the
      Rh-C and Pt-C ones in all surface species. The observed stretching wavenumbers
      and force constants seem to support the idea that CO and metal-carbon bonds are
      always stronger in metal carbonyl complexes than in adsorbed surface species. The
      distribution and mode of CO adsorption on surface metal sites can be effectively
      studied by means of infrared emission spectroscopy.

PMID- 16451014
TI  - Experimental and theoretical 17O NMR study of the influence of hydrogen-bonding
      on C=O and O-H oxygens in carboxylic solids.
AB  - A systematic solid-state 17O NMR study of a series of carboxylic compounds,
      maleic acid, chloromaleic acid, KH maleate, KH chloromaleate, K2 chloromaleate,
      and LiH phthalate.MeOH, is reported. Magic-angle spinning (MAS), triple-quantum
      (3Q) MAS, and double angle rotation (DOR) 17O NMR spectra were recorded at high
      magnetic fields (14.1 and 18.8 T). 17O MAS NMR for metal-free carboxylic acids
      and metal-containing carboxylic salts show featured spectra and demonstrate that
      this combined, where necessary, with DOR and 3QMAS, can yield site-specific
      information for samples containing multiple oxygen sites. In addition to 17O NMR
      spectroscopy, extensive quantum mechanical calculations were carried out to
      explore the influence of hydrogen bonding at these oxygen sites. B3LYP/6
      311G++(d,p) calculations of 17O NMR parameters yielded good agreement with the
      experimental values. Linear correlations are observed between the calculated 17O
      NMR parameters and the hydrogen bond strengths, suggesting the possibility of
      estimating H-bonding information from 17O NMR data. The calculations also
      revealed intermolecular H-bond effects on the 17O NMR shielding tensors. It is
      found that the delta11 and delta22 components of the chemical shift tensor at O-H
      and C=O, respectively, are aligned nearly parallel with the strong H-bond and
      shift away from this direction as the H-bond interaction weakens.

PMID- 16451015
TI  - Ion-neutral potential models in atmospheric pressure ion mobility time-of-flight
      mass spectrometry IM(tof)MS.
AB  - The ion mobilities and their respective masses of several classes of amines
      (primary, secondary, and tertiary) were measured by electrospray ionization
      atmospheric pressure ion mobility time-of-flight mass spectrometry IM(tof)MS. The
      experimental data obtained were comparatively analyzed by the one-temperature
      kinetic theory of Chapman-Enskog. Several theoretical models were used to
      estimate the collision cross-sections; they include the rigid-sphere,
      polarization-limit, 12-6-4, and 12-4 potential models. These models were
      investigated to represent the interaction potentials contained within the
      collision integral that occurs between the polyatomic ions and the neutral drift
      gas molecules. The effectiveness of these collision cross-section models on
      predicting the mobility of these amine ions was explored. Moreover, the effects
      of drift gas selectivity on the reduced-mass term and in the collision cross
      section term was examined. Use of a series of drift gases, namely, helium, neon,
      argon, nitrogen, and carbon dioxide, made it possible to distinguish between mass
      effects and polarizability effects. It was found that the modified 12-4 potential
      that compensates for the center of charge not being at the same location as the
      centers of mass showed improved agreement over the other collision cross-section
      models with respect to experimental data.

PMID- 16451016
TI  - Noble gas-transition-metal complexes: coordination of VO2 and VO4 by Ar and Xe
      atoms in solid noble gas matrixes.
AB  - The matrix isolation infrared spectroscopic and quantum chemical calculation
      results indicate that vanadium oxides, VO2 and VO4, coordinate noble gas atoms in
      forming noble gas complexes. The results showed that VO2 coordinates two Ar or Xe
      atoms and that VO4 coordinates one Ar or Xe atom in solid noble gas matrixes.
      Hence, the VO2 and VO4 molecules trapped in solid noble gas matrixes should be
      regarded as the VO2(Ng)2 and VO4(Ng) (Ng = Ar or Xe) complexes. The total V-Ng
      binding energies were predicted to be 12.8, 18.2, 5.0, and 7.3 kcal/mol,
      respectively, for the VO2(Ar)2, VO2(Xe)2, VO4(Ar), and VO4(Xe) complexes at the
      CCSD(T)//B3LYP level of theory.

PMID- 16451017
TI  - Infrared spectra and density functional calculations for the Sc(OH)2,3 and HOScO
      molecules and the Sc(OH)2+ cation in solid argon.
AB  - Reactions of laser-ablated Sc atoms with H2O2 molecules or H2 and O2 mixtures in
      excess solid argon gives four major new products, which are identified from
      concentration dependence, isotopic substitution, the effect of electron trap
      doping, and comparison to frequencies calculated by the B3LYP density functional.
      These are the Sc(OH)3 trihydroxide, the Sc(OH)2 dihydroxide, the Sc(OH)2+ cation,
      and the trihydroxide anhydride HOScO molecule. The Sc(OH)2+ cation forms a
      complex in solid argon that is effectively modeled by calculations for the
      [(Ar)4Sc(OH)2]+ cation including frequency shifts between the neutral and cation
      dihydroxides. Finally, the Sc(OH)4- anion is detected in H2O2 experiments.

PMID- 16451018
TI  - Gas-phase molecular halogen formation from NaCl and NaBr aerosols: when are
      interface reactions important?
AB  - Unique interface reactions at the surface of sea-salt particles have been
      suggested as an important source of photolyzable gas-phase halogen species in the
      troposphere. Many factors influence the relative importance of interface
      chemistry compared to aqueous-phase chemistry. The Model of Aerosol, Gas, and
      Interfacial Chemistry (MAGIC 2.0) is used to study the influence of interface
      reactions on gas-phase molecular halogen production from pure NaCl and NaBr
      aerosols. The main focus is to identify the relative importance of bulk compared
      to interface chemistry and to determine when interface chemistry dominates.
      Results show that the interface process involving Cl-(surf) and OH(g) is the main
      source of Cl2(g). For the analogous oxidation of bromide by OH, gaseous Br2 is
      formed mainly in the bulk aqueous phase and transferred across the interface.
      However, the reaction of Br-(surf) with O3(g) at the interface is the primary
      source of Br2(g) under dark conditions. The effect of aerosol size is also
      studied. Potential atmospheric implications and effects of interface processes on
      aerosol pH are discussed.

PMID- 16451019
TI  - Quantum chemical study of solvent and substituent effects on the 1,5-hydride
      shift in 2,6-dimethyl-2-heptyl cations.
AB  - The mechanism of the degenerate 1,5-hydride shift in 2,6-dimethyl-2-heptyl
      cations has been investigated using ab initio MP2 and density functional theory
      (DFT) hybrid (B3LYP) calculations. The potential-energy profile for the 1,5
      hydride shift consists of three minima corresponding to two equivalent acyclic
      carbocations and one symmetrically mu-hydrido-bridged carbocation, while two
      equivalent unsymmetrically hydrido-bridged carbocations were located as
      transition-state structures. The calculated relative energy differences between
      acyclic carbocations and symmetrically mu-hydrido-bridged structure are
      significantly affected by introduction of alkyl and (CH2)n-substituents at the C4
      position of the 2,6-dimethyl-2-heptyl cation structure. DFT self-consistent
      isodensity polarizable continuum method (SCI-PCM) and MP2 PCM continuum methods
      have been used to calculate the effect of solvation on geometries and relative
      energies of the species involved in the 1,5-hydride shift. It is found that
      relative energies of acyclic and mu-hydrido-bridged carbocation structures as
      well as the energy barriers for 1,5-hydride shifts are in accord with
      experimental data if solvation effects are taken into account.

PMID- 16451020
TI  - Low-temperature rate coefficients for the reaction of ethynyl radical (C2H) with
      benzene.
AB  - The reaction of the C2H radical with benzene is studied at low temperature using
      a pulsed Laval nozzle apparatus. The C2H radical is prepared by 193-nm photolysis
      of acetylene, and the C2H concentration is monitored using CH(A2Delta)
      chemiluminescence from the C2H + O2 reaction. Measurements at very low photolysis
      energy are performed using CF3C2H as the C2H precursor to study the influence of
      benzene photodissociation on the rate coefficient. Rate coefficients are obtained
      over a temperature range between 105 and 298 K. The average rate coefficient is
      found to be five times greater than the estimated value presently used in the
      photochemical modeling of Titan's atmosphere. The reaction exhibits a slight
      negative temperature dependence which can be fitted to the expression k(cm3
      molecule(-1) s(-1)) = 3.28(+/-1.0) x 10(-10) (T/298)(-0.18(+/-0.18)). The results
      show that this reaction has no barrier and may play an important role in the
      formation of large molecules and aerosols at low temperature. Our results are
      consistent with the formation of a short lifetime intermediate that decomposes to
      give the final products.

PMID- 16451021
TI  - Phase changes during hygroscopic cycles of mixed organic/inorganic model systems
      of tropospheric aerosols.
AB  - A correct description of the aerosol's phases is required to determine its
      gas/particle partitioning, its reactivity and its water uptake and release. In
      this study, we investigate organic/electrolyte interactions of ammonium sulfate,
      nitrate and sodium chloride with substances containing carboxylic acids (COOH)
      and hydroxyl (OH) functional groups. As organic model compounds, we chose polyols
      with different OH/CHn (n = 0-3) ratios-namely, glycerol, 1,4-butanediol, and 1,2
      hexanediol-as well as PEG 400 and a mixture of dicarboxylic acids consisting of
      malic, malonic, maleic, glutaric, and methylsuccinic acid. Bulk solubility and
      water activity measurements of these model systems together with a survey of
      literature data showed that NaCl is a salting-out agent for alcohols and organic
      acids whereas ammonium nitrate and sulfate exhibited salting-in and salting-out
      tendencies depending on the nature and number of functional groups as well as on
      the concentration of the solution. All investigated salts induce a liquid-liquid
      phase separation in the 1,2-hexanediol/water system. Considering the composition
      of the tropospheric aerosol, such phase separations might indeed occur frequently
      when particles in the atmosphere are exposed to varying relative humidity. To
      complement the bulk experiments, we investigated single particles consisting of
      ammonium sulfate and dicarboxylic acids as well as of ammonium sulfate and PEG
      400 in an electrodynamic balance. Whereas the relative humidities of total
      deliquescence as well as the water uptake and release of the fully deliquesced
      particles are in good agreement with the bulk results and represent thermodynamic
      equilibrium, the water uptake before full deliquescence shows significant
      deviations. These deviations may be caused by morphological effects.

PMID- 16451023
TI  - Rates and mechanisms of conversion of ice nanocrystals to ether clathrate
      hydrates: guest-molecule catalytic effects at approximately 120 k.
AB  - A Fourier transform infrared investigation of the rates and energetics of
      conversion of ice nanocrystals within 3-D arrays to ether clathrate-hydrate (CH)
      particles at approximately 120 K is reported. After an induction period,
      apparently necessitated by relatively slow nucleation of the CH phase, the well
      established shrinking-core model of particle-adsorbate reaction applies to these
      conversions in the presence of an abundance of adsorbed ether. This implies that
      the transport of the ether adsorbate through the product crust encasing a
      reacting particle core (a necessary aspect of a particle reaction mechanism) is
      the rate-controlling factor. Diffusion moves adsorbed reactant molecules to the
      reaction zone at the interface of the ice core with the product (CH) crust. The
      results indicate that ether hydrate formation rates near 120 K resemble rates for
      gas hydrates measured near 260 K, implying rates greater by many orders of
      magnitude for comparable temperatures. A surprising secondary enhancement of
      ether CH-formation rates by the simultaneous incorporation of simple small gas
      molecules (N2, CO2, CH4, CO, and N2O) has also been quantified in this study. The
      rapid CH formation at low temperatures is conjectured to derive from defect
      facilitated transport of reactants to an interfacial reaction zone, with the
      defect populations enhanced through transient H bonding of guest-ether proton
      acceptor groups with O-H groups of the hydrate cage walls.

PMID- 16451022
TI  - Effect of pH on one-electron oxidation chemistry of organoselenium compounds in
      aqueous solutions.
AB  - Pulse radiolysis coupled with absorption detection has been employed to study one
      electron oxidation of selenomethionine (SeM), selenocystine (SeCys), methyl
      selenocysteine (MeSeCys), and selenourea (SeU) in aqueous solutions. Hydroxyl
      radicals (*OH) in the pH range from 1 to 7 and specific one-electron oxidants
      Cl2*- (pH 1) and Br2*- (pH 7) have been used to carry out the oxidation
      reactions. The bimolecular rate constants for these reactions were reported to be
      in the range of 2 x 10(9) to 10 x 10(9) M(-1) s(-1). Reactions of oxidizing
      radicals with all these compounds produced selenium-centered radical cations. The
      structure and stability of the radical cation were found to depend mainly on the
      substituent and pH. SeM, at pH 7, produced a monomer radical cation (lambdamax
      approximately 380 nm), while at pH 1, a dimer radical cation was formed by the
      interaction between oxidized and parent SeM (lambdamax approximately 480 nm).
      Similarly, SeCys, at pH 7, on one-electron oxidation, produced a monomer radical
      cation (lambdamax approximately 460 nm), while at pH 1, the reaction produced a
      transient species with (lambdamax approximately 560 nm), which is also a monomer
      radical cation. MeSeCys on one-electron oxidation in the pH range from 1 to 7
      produced monomer radical cations (lambdamax approximately 350 nm), while at pH <
      0, the reaction produced dimer radical cations (lambdamax approximately 460 nm).
      SeU at all the pH ranges produced dimer radical cations (lambdamax approximately
      410 nm). The association constants of the dimer radical cations of SeM, MeSeCys,
      and SeU were determined by following absorption changes at lambdamax as a
      function of concentration. From these studies it is concluded that formation of
      monomer and dimer radical cations mainly depends on the substitution, pH, and the
      heteroatoms like N and O. The availability of a lone pair on an N or O atom at
      the beta or gamma position results in monomer radical cations having
      intramolecular stabilization. When such a lone pair is not available, the monomer
      radical cation is converted into a dimer radical cation which acquires
      intermolecular stabilization by the other selenium atom. The pH dependency
      confirms the role of protonation on stabilization. The oxidation chemistry of
      these selenium compounds is compared with that of their sulfur analogues.

PMID- 16451024
TI  - Experimental investigation of the homogeneous freezing of aqueous ammonium
      sulfate droplets.
AB  - We have measured the light scattering intensity and homogeneous ice nucleation
      temperatures from water droplets containing 0-33 wt % ammonium sulfate. In these
      laboratory experiments, we used a free-fall freezing tube technique to determine
      the fraction of frozen droplets at a particular droplet temperature by measuring
      the depolarized light scattering intensity from the droplets in free-fall.
      Previously reported freezing temperatures for solution concentrations greater
      than 5 wt % display a larger spread than can be accounted for by the reported
      experimental errors. We find freezing temperatures in good agreement with the
      lowest temperature freezing results reported by previous experiments. Our
      ammonium sulfate freezing temperature data set with water activity less than 0.98
      is consistent with a curve that deviates in activity shift by about 5% from the
      best-fit ice nucleation temperature versus water activity curve found by Koop et
      al. in 2000, but the significance of this deviation will only be known with
      further high-precision ice nucleation temperature measurements for other aqueous
      solutions.

PMID- 16451025
TI  - Isopropylcyclopropane + OH gas phase reaction: a quantum chemistry + CVT/SCT
      approach.
AB  - A theoretical study of the mechanism and kinetics of the OH hydrogen abstraction
      from isopropylcyclopropane (IPCP) is presented. Optimum geometries, frequencies
      and gradients have been computed at the BHandHLYP/6-311++G(d,p) level of theory
      for all stationary points, as well as for additional points along the minimum
      energy path (MEP). Energies have been improved by single-point calculations at
      the above geometries using CCSD(T)/6-311++G(d,p) to produce the potential energy
      surface. The rate coefficients are calculated for the temperature range 260-350 K
      by using canonical variational theory (CVT) with small-curvature tunneling (SCT)
      corrections. Our analysis suggests a stepwise mechanism involving the formation
      of a reactant complex in the entrance channel and a product complex in the exit
      channel, for all the modeled paths. The reactant complexes are examined in
      detail, because they exhibit alkene-like structure. The excellent agreement
      between the overall calculated and experimental rate coefficients at 298 K
      supports the reliability of the parameters obtained for the temperature
      dependence and branching ratios of the IPCP + OH reaction, proposed here for the
      fist time. The expression that best describes the studied reaction is k(overall)
      = 6.15 x 10(-13)e1747/RT cm3 x molecule(-1) x s(-1). The predicted activation
      energy is -0.89 kcal/mol.

PMID- 16451026
TI  - Theoretical UV circular dichroism of cyclo(L-Proline-L-Proline).
AB  - MP2, DFT, and molecular mechanics (AMBER, CVFF, and CFF91) geometry optimizations
      were performed on the cyclic dipeptide cyclo(L-Pro-L-Pro) starting from crystal
      structure data. Three stable conformations were identified as energy minima by
      all methods, but assignment of relative energy varied between the methods. The pi
      pi transition feature of the UV circular dichroic (CD) spectrum was predicted for
      each minimized structure using the classical physics method of the dipole
      interaction model. The model was sensitive to the different conformations. The UV
      CD predictions were compared individually and as a Boltzmann-weighted composite
      with published experimental CD spectra [Bowman, R. L.; Kellerman, M.; Johnson, W.
      C., Jr. Biopolymers 1983, 22, 1045]. For all structures, the original parameters
      of Applequist [Applequist, J. J. Chem. Phys. 1979, 71, 4324] with a bandwidth of
      3000 cm(-1) most accurately replicated experiment, except for the CFF91
      structures, which matched experiment best with a bandwidth of 4000 cm(-1). The
      inclusion of solvent by a continuum model did not significantly alter the
      minimized geometries obtained by molecular or quantum mechanics, but it did have
      an effect on the relative predicted energies of CFF91 and B3LYP conformations.
      The overall effect of solvent inclusion was negligible when Boltzmann-weighted
      spectra were considered. Gas-phase CFF91 structures were also reasonably good for
      prediction of CD spectra, and when water was included via a continuum model for
      energy calculations, the weighting scheme resembled that of the higher-level
      weightings. The CD calculated using the MP2/6-311G structures and energies for
      weighting were most descriptive of the 180 nm negative band in the experimental
      CD, but red-shifted the location of the 205 nm band. DFT structures were
      comparably, though not identically, as descriptive of the first pi-pi band, and
      did a better job with placement of the second (positive) pi-pi band. DFT
      calculations were less sensitive to basis set effect than the MP2 calculations,
      with 6-31G results in close agreement with 6-311G. The results suggest that it is
      possible to use geometries obtained from a variety of different methods
      (molecular mechanical or quantum mechanical) with the classical physics dipole
      interaction model to qualitatively reproduce the UV CD of model amides.

PMID- 16451027
TI  - pi --> n fluorescence transition in formaldehyde in aqueous solution: a combined
      quantum chemical statistical mechanical study.
AB  - The solvent shift to the fluorescence transition pi --> n in formaldehyde in
      aqueous solution is theoretically analyzed. The solvent model has explicit
      representation of the solvent and uses the complete active space state
      interaction (CASSI) method to obtain a description of the wave function of the
      solute similar to what the complete active space self-consistent-field (CASSCF)
      method would give. In the description of the solute-solvent interaction the
      discrete set of solvent molecules perturb the solute not only through an
      electrostatic perturbation but also through a nonelectrostatic operator. The
      latter describes in a way analogous to pseudopotential theory the effect the
      Pauli principle has on the solute embedded in the solvent. This way the exchange
      repulsion between solute and solvent is accounted for which therefore can be
      anisotropic. The best estimate of the average shift is a blue shift of 0.003 eV,
      and for the current transition the nonelectrostatic perturbation broadens the
      distribution but has no significant effect on the average shift.

PMID- 16451028
TI  - Gas-phase deprotonation of uracil-Cu2+ and thiouracil-Cu2+ complexes.
AB  - The deprotonation of Cu2+ complexes with uracil, 2-thiouracil, 4-thiouracil, and
      2,4-dithiouracil has been investigated by means of B3LYP/ 6-311+G(2df,2p)//6
      31G(d) calculations. The most stable [(uracil-H)Cu]+ and [(thiouracil-H)Cu]+
      complexes correspond to bidentate structures in which Cu interacts with the
      deprotonated ring-nitrogen atom and with the oxygen or the sulfur atom of the
      adjacent carbonyl or thiocarbonyl group. For 2- and 4-thiouracil derivatives, the
      structures in which the metal cation interacts with the thiocarbonyl group are
      clearly favored with respect to those in which Cu interacts with the carbonyl
      group. This is at variance with what was found to be the most stable structure of
      the corresponding Cu2+ complexes, where association to the carbonyl oxygen was
      always preferred over the association to the thiocarbonyl group. The [(uracil
      H)Cu]+ and [(thiouracil-H)Cu]+ complexes can be viewed as the result of Cu+
      attachment to the uracil-H and thiouracil-H radicals formed by the deprotonation
      of the corresponding uracil+* and thiouracil+* radical cations. As a matter of
      fact their relative stability is dictated by the intrinsic stability of the
      corresponding uracil-H and thiouracil-H radical and by the fact that, in general,
      the N3-deprotonated site is a better electron donor than the N1. In all
      complexes, the bonding of Cu both to nitrogen and sulfur and to nitrogen and
      oxygen has a significantly large covalent character.

PMID- 16451030
TI  - Effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+) and water
      coordination on the structure of glycine and zwitterionic glycine.
AB  - Interactions between metal ions and amino acids are common both in solution and
      in the gas phase. Here, the effect of metal ions and water on the structure of
      glycine is examined. The effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+,
      Cu2+, and Zn2+) and water on structures of Gly.Mn+(H2O)m and GlyZwitt.Mn+(H2O)m
      (m = 0, 2, 5) complexes have been determined theoretically by employing the
      hybrid B3LYP exchange-correlation functional and using extended basis sets.
      Selected calculations were carried out also by means of CBS-QB3 model chemistry.
      The interaction enthalpies, entropies, and Gibbs energies of eight complexes
      Gly.Mn+ (Mn+ = Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+) were determined at
      the B3LYP density functional level of theory. The computed Gibbs energies DeltaG
      degrees are negative and span a rather broad energy interval (from -90 to -1100
      kJ mol(-1)), meaning that the ions studied form strong complexes. The largest
      interaction Gibbs energy (-1076 kJ mol(-1)) was computed for the NiGly2+ complex.
      Calculations of the molecular structure and relative stability of the
      Gly.Mn+(H2O)m and GlyZwitt.Mn+(H2O)m (Mn+ = Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+,
      and Zn2+; m = 0, 2, and 5) systems indicate that in the complexes with monovalent
      metal cations the most stable species are the NO coordinated metal cations in non
      zwitterionic glycine. Divalent cations Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+ prefer
      coordination via the OO bifurcated bonds of the zwitterionic glycine. Stepwise
      addition of two and five water molecules leads to considerable changes in the
      relative stability of the hydrated species. Addition of two water molecules at
      the metal ion in both Gly.Mn+ and GlyZwitt.Mn+ complexes reduces the relative
      stability of metallic complexes of glycine. For Mn+ = Li+ or Na+, the addition of
      five water molecules does not change the relative order of stability. In the
      Gly.K+ complex, the solvation shell of water molecules around K+ ion has, because
      of the larger size of the potassium cation, a different structure with a reduced
      number of hydrogen-bonded contacts. This results in a net preference (by 10.3 kJ
      mol(-1)) of the GlyZwitt.K+H2O5 system. Addition of five water molecules to the
      glycine complexes containing divalent cations Mg2+, Ca2+, Ni2+, Cu2+, and Zn2+
      results in a net preference for non-zwitterionic glycine species. The computed
      relative Gibbs energies are quite high (-10 to -38 kJ mol(-1)), and the NO
      coordination is preferred in the Gly.Mn+(H2O)5 (Mn+ = Mg2+, Ca2+, Ni2+, Cu2+, and
      Zn2+) complexes over the OO coordination.

PMID- 16451031
TI  - Accurate heats of formation of the "Arduengo-type" carbene and various adducts
      including H2 from ab initio molecular orbital theory.
AB  - The heats of formation of saturated and unsaturated diaminocarbenes (imadazol(in)
      2-ylidenes) have been calculated by using high levels of ab initio electronic
      structure theory. The calculations were done at the coupled cluster level through
      noniterative triple excitations with augmented correlation consistent basis sets
      up through quadruple. In addition, four other corrections were applied to the
      frozen core atomization energies: (1) a zero point vibrational correction; (2) a
      core/valence correlation correction; (3) a scalar relativistic correction; (4) a
      first-order atomic spin-orbit correction. The value of DeltaHf( 298) for the
      unsaturated carbene 1 is calculated to be 56.4 kcal/mol. The value of DeltaHf(
      298) for the unsaturated triplet carbene (3)1 is calculated to be 142.8 kcal/mol,
      giving a singlet-triplet splitting of 86.4 kcal/mol. Addition of a proton to 1
      forms 3 with DeltaHf( 298)(3) = 171.6 kcal/mol with a proton affinity for 1 of
      250.5 kcal/mol at 298 K. Addition of a hydrogen atom to 1 forms 4 with DeltaHf(
      298)(4) = 72.7 kcal/mol and a C-H bond energy of 35.8 kcal/mol at 298 K. Addition
      of H- to 1 gives 5 with DeltaHf( 298)(5) = 81.2 kcal/mol and 5 is not stable with
      respect to loss of an electron to form 4. Addition of H2 to the carbene center
      forms 6 with DeltaHf( 298)(6) = 41.5 kcal/mol and a heat of hydrogenation at 298
      K of -14.9 kcal/mol. The value of DeltaHf( 298) for the saturated carbene 7
      (obtained by adding H2 to the C=C bond of 1) is 47.4 kcal/mol. Hydrogenation of 7
      to form the fully saturated imidazolidine, 8, gives DeltaHf( 298)(8) = 14.8
      kcal/mol and a heat of hydrogenation at 298 K of -32.6 kcal/mol. The estimated
      error bars for the calculated heats of formation are +/-1.0 kcal/mol.

PMID- 16451029
TI  - Solid-state modeling of the terahertz spectrum of the high explosive HMX.
AB  - The experimental solid-state terahertz (THz) spectrum (3-120 cm(-1)) of the beta
      crystal form of the high explosive octahydro-1,3,5,7-tetranitro-1,3,5,7
      tetrazocine (HMX) has been analyzed using solid-state density functional theory
      calculations. Various density functionals (both generalized gradient
      approximation and local density approximation) are compared in terms of their
      abilities to reproduce the experimentally observed solid-state structure and low
      frequency vibrational motions. Good-to-excellent agreement between solid-state
      theory and experiment can be achieved in the THz region where isolated-molecule
      calculations fail to reproduce the observed spectral features, demonstrating a
      clear limitation of using isolated-molecule calculations for the assignment of
      THz frequency motions in molecular solids. The deficiency of isolated-molecule
      calculations is traced to modification of the molecular structure in the solid
      state through crystal packing effects and the formation of weak C-H...O hydrogen
      bonds.

PMID- 16451032
TI  - Reliable electron affinities of perfluorocyclopropane and perfluorocyclobutane
      from convergent ab initio computations.
AB  - To resolve discrepancies concerning the magnitude of the electron affinities of
      perfluorocyclopropane and perfluorocyclobutane, quantum chemical calculations
      have been carried out with the MP2 and CCSD(T) methods in conjunction with
      augmented correlation consistent basis sets (aug-cc-pVX Z, X = D, T, Q). Though
      no experimental values have been found for perfluorocyclopropane, we estimate its
      electron affinity to be 0.17 eV (0.00 eV without zero-point vibrational energy
      corrections). In addition, determination of the electron affinity of
      perfluorocyclobutane (0.61 and 0.44 eV with and without zero-point vibrational
      energy corrections, respectively) is in good agreement with experimental values
      reported by Miller and co-workers (0.63 +/- 0.05 eV). This study also
      demonstrates that the widely prescribed B3LYP/DZP++ model chemistry for computing
      electron affinities does not correctly describe these systems.

PMID- 16451033
TI  - Solvation of yttrium with ammonia revisited. Di-amide formation in the reaction
      of yttrium with ammonia.
AB  - The reactivity of yttrium atoms toward ammonia is revisited using expanded
      density functional theory calculations. The new results reveal that absorption of
      NH3 on YNH is dissociative to form Y(NH2)2. The di-amide species can adsorb
      further NH3 molecules molecularly to form Y(NH2)2NH3 and Y(NH2)2(NH3)2. The
      calculations aimed to reveal the detail of the potential energy curves between
      the imide and the di-amide forms. The Y(NH2)2(NH3)x species are more stable than
      those of YNH(NH3)x by more than 20 kcal/mol.

PMID- 16451034
TI  - Hydrogen transfer between sulfuric acid and hydroxyl radical in the gas phase:
      competition among hydrogen atom transfer, proton-coupled electron-transfer, and
      double proton transfer.
AB  - In an attempt to assess the potential role of the hydroxyl radical in the
      atmospheric degradation of sulfuric acid, the hydrogen transfer between H2SO4 and
      HO* in the gas phase has been investigated by means of DFT and quantum-mechanical
      electronic-structure calculations, as well as classical transition state theory
      computations. The first step of the H2SO4 + HO* reaction is the barrierless
      formation of a prereactive hydrogen-bonded complex (Cr1) lying 8.1 kcal mol(-1)
      below the sum of the (298 K) enthalpies of the reactants. After forming Cr1, a
      single hydrogen transfer from H2SO4 to HO* and a degenerate double hydrogen
      exchange between H2SO4 and HO* may occur. The single hydrogen transfer, yielding
      HSO4* and H2O, can take place through three different transition structures, the
      two lowest energy ones (TS1 and TS2) corresponding to a proton-coupled electron
      transfer mechanism, whereas the higher energy one (TS3) is associated with a
      hydrogen atom transfer mechanism. The double hydrogen-exchange, affording
      products identical to reactants, takes place through a transition structure (TS4)
      involving a double proton-transfer mechanism and is predicted to be the dominant
      pathway. A rate constant of 1.50 x 10(-14) cm(3) molecule(-1) s(-1) at 298 K is
      obtained for the overall reaction H2SO4 + HO*. The single hydrogen transfer
      through TS1, TS2, and TS3 contributes to the overall rate constant at 298 K with
      a 43.4%. It is concluded that the single hydrogen transfer from H2SO4 to HO*
      yielding HSO4* and H2O might well be a significant sink for gaseous sulfuric acid
      in the atmosphere.

PMID- 16451035
TI  - Theoretical models on the Cu2O2 torture track: mechanistic implications for
      oxytyrosinase and small-molecule analogues.
AB  - Accurately describing the relative energetics of alternative bis(mu-oxo) and mu
      eta2:eta2 peroxo isomers of Cu2O2 cores supported by 0, 2, 4, and 6 ammonia
      ligands is remarkably challenging for a wide variety of theoretical models,
      primarily owing to the difficulty of maintaining a balanced description of
      rapidly changing dynamical and nondynamical electron correlation effects and a
      varying degree of biradical character along the isomerization coordinate. The
      completely renormalized coupled-cluster level of theory including triple
      excitations and extremely efficient pure density functional levels of theory
      quantitatively agree with one another and also agree qualitatively with
      experimental results for Cu2O2 cores supported by analogous but larger ligands.
      Standard coupled-cluster methods, such as CCSD(T), are in most cases considerably
      less accurate and exhibit poor convergence in predicted relative energies. Hybrid
      density functionals significantly underestimate the stability of the bis(mu-oxo)
      form, with the magnitude of the error being directly proportional to the
      percentage Hartree-Fock exchange in the functional. Single-root CASPT2
      multireference second-order perturbation theory, by contrast, significantly
      overestimates the stability of bis(mu-oxo) isomers. Implications of these results
      for modeling the mechanism of C-H bond activation by supported Cu2O2 cores, like
      that found in the active site of oxytyrosinase, are discussed.

PMID- 16451036
TI  - Quantum chemical modeling of the reduction of quinones.
AB  - A systematic study of the redox properties of six parent quinones has been
      carried out using quantum chemistry methods. The reduction of the ortho (o-) and
      para (p-) isomers of benzoquinone and naphthoquinone, 9,10- anthraquinone and
      9,10-phenantrenequinone to the corresponding hydroquinones and semiquinone
      radicals was investigated at the B3LYP/6-311+G(d,p) level of theory.
      Thermodynamic functions in the gas-phase were calculated for all the reduction
      reactions. Gibbs energies of reaction and standard potentials in water for the
      reductions were determined using the IEF-PCM model and an empirical correction to
      the calculations based on the limited thermodynamic data available for the
      quinones. Potentials were calculated both for the direct reduction to the
      quinols, and for the two-step reduction via the neutral semiquinones. The
      calculated potentials for the 2e-, 2H+ reductions were found in good agreement
      with experiment and to display the same trends as gas-phase enthalpies and
      energies, i.e., to correlate with the number of C=C double bonds, as well as on
      the relative position of the C=O groups. The small deviations between experiment
      and theoretically predicted standard potentials were found to originate from
      basis set incompleteness and the shortcomings in the B3LYP exchange correlation
      functional rather than the models used for the thermochemical calculations or
      description of solvation. Accurate theoretical shifts in standard potentials for
      the p-/o- pairs of Q <--> HQ and HQ <--> H2Q reactions are presented and compared
      to experiment. Reliable standard potentials and shifts for the neutral
      semiquinones are predicted for the first time.

PMID- 16451037
TI  - An investigation of chlorophenol proton affinities and their influence on the
      biological activity of microorganisms.
AB  - The proton affinities of 15 chlorophenols are calculated by ab initio methods.
      Straight correlation between proton affinities and changes in the electronic
      structure is observed. The proton affinities decrease linearly with the
      electronic density gain on the chlorine atoms, as the liberation of the proton
      increases. To confirm the importance of the proton affinities on the toxicity of
      chlorophenols, calorimetric responses of these molecules and related ones where
      the acid proton is changed to a methyl group (anisol and its chlorinated
      derivatives) were used to verify their effects on Chromobacterium violaceum. The
      results confirmed that the chlorophenols are more toxic than the respective
      chloroanisols and suggest that high proton affinities are associated with low
      toxic activity. The toxicity of the chlorophenols can be associated with the
      respiratory mechanism in some microorganisms.

PMID- 16451038
TI  - Intermolecular interaction between hexafluorobenzene and benzene: Ab initio
      calculations including CCSD(T) level electron correlation correction.
AB  - The intermolecular interaction energy of hexafluorobenzene-benzene has been
      calculated with the ARS-E model (a model chemistry for the evaluation of the
      intermolecular interaction energy between aromatic systems using extrapolation),
      which was formerly called the AIMI model. The CCSD(T) interaction energy at the
      basis-set limit has been estimated from the MP2 interaction energy at the basis
      set limit and the CCSD(T) correction term obtained using a medium-sized basis
      set. The slipped-parallel (Cs) complex has the largest (most negative)
      interaction energy (-5.38 kcal/mol). The sandwich (C6v) complex is slightly less
      stable (-5.07 kcal/mol). The interaction energies of two T-shaped (C2v) complexes
      are very small (-1.74 and -0.88 kcal/mol). The calculated interaction energy of
      the slipped-parallel complex is about twice as large as that of the benzene
      dimer. The dispersion interaction is found to be the major source of attraction
      in the complex, although electrostatic interaction also contributes to the
      attraction. The dispersion interaction increases the relative stability of the
      slipped-parallel benzene dimer and the hexafluorobenzene-benzene complex compared
      to T-shaped ones. The electrostatic interaction is repulsive in the slipped
      parallel benzene dimer, whereas it stabilizes the slipped-parallel
      hexafluorobenzene-benzene complex. Both electrostatic and dispersion interactions
      stabilize the slipped-parallel hexafluorobenzene-benzene complex, which is the
      cause of the preference of the slipped-parallel orientation and the larger
      interaction energy of the complex compared to the benzene dimer.

PMID- 16451039
TI  - Stability and thermal rearrangement of (E,E)-1,3-cycloheptadiene and trans
      bicyclo[3.2.0]hept-6-ene.
AB  - The highly strained (E,E)-1,3-cycloheptadiene was shown to be a minimum on the
      potential energy surface; two structural isomers were found at the MP2 level, but
      multiconfiguration self-consistent field calculations show that only one is a
      true minimum. The isomerization of (E,E)-1,3-cycloheptadiene was investigated
      through double bond rotation, and electrocyclic ring closure. The first pathway
      gives (E,Z)-1,3-cycloheptadiene, with a barrier of 7.2 kcal x mol(-1), and the
      second pathway gives the trans isomer of bicyclo[3.2.0]hept-6-ene with a barrier
      of 13.0 kcal x mol(-1). The strain energy of (E,E)-1,3-cycloheptadiene was
      calculated using homodesmotic reactions and found to be about 96 kcal x mol(-1)
      whereas that for (E,Z)-1,3-cycloheptadiene was only 38 kcal x mol(-1), implying
      that the second trans double bond imparts an additional 58 kcal x mol(-1) in
      strain energy. The trans isomer of bicyclo[3.2.0]hept-6-ene was calculated to
      have a strain energy of 69 kcal x mol(-1) and a barrier of 27 kcal x mol(-1) for
      isomerization to (Z,Z)-1,3-cycloheptadiene. Although many of the structures
      reported here could be described using a single determinant wave function,
      several could not, making a multireference method necessary for a complete
      description of the potential energy surface.

PMID- 16451040
TI  - Molecular structures and electronic transitions of 3,6-diphenyl-1,2-dithiin and
      its radical cation: a spectroelectrochemical and DFT study.
AB  - One-electron oxidation of 3,6-diphenyl-1,2-dithiin yields the corresponding
      radical cation. The product is stable at low temperatures and can be
      distinguished by a triplet EPR signal. Cyclic voltammetric, UV-vis
      spectroelectrochemical, and DFT studies were performed to elucidate its molecular
      structure and electronic properties. Time-dependent DFT calculations reproduce
      appreciably well the UV-vis spectral changes observed during the oxidation. The
      results reveal a moderately twisted structure of the 1,2-dithiin heterocycle in
      the radical cation.

PMID- 16451041
TI  - Molecular structure and benzene ring deformation of three ethynylbenzenes from
      gas-phase electron diffraction and quantum chemical calculations.
AB  - The molecular structures of ethynylbenzene and s-triethynylbenzene have been
      accurately determined by gas-phase electron diffraction and ab initio/DFT MO
      calculations and are compared to that of p-diethynylbenzene from a previous study
      [Domenicano, A.; Arcadi, A.; Ramondo, F.; Campanelli, A. R.; Portalone, G.;
      Schultz, G.; Hargittai, I. J. Phys. Chem. 1996, 100, 14625]. Although the
      equilibrium structures of the three molecules have C2v, D3h, and D2h symmetry,
      respectively, the corresponding average structures in the gaseous phase are best
      described by nonplanar models of Cs, C3v, and C2v symmetry, respectively. The
      lowering of symmetry is due to the large-amplitude motions of the substituents
      out of the plane of the benzene ring. The use of nonplanar models in the electron
      diffraction analysis yields ring angles consistent with those from MO
      calculations. The molecular structure of ethynylbenzene reported from microwave
      spectroscopy studies is shown to be inaccurate in the ipso region of the benzene
      ring. The variations of the ring C-C bonds and C-C-C angles in p-diethynylbenzene
      and s-triethynylbenzene are well interpreted as arising from the superposition of
      independent effects from each substituent. In particular, experiments and
      calculations consistently show that the mean length of the ring C-C bonds
      increases by about 0.002 A per ethynyl group. MO calculations at different levels
      of theory indicate that though the length of the C[triple bond]C bond of the
      ethynyl group is unaffected by the pattern of substitution, the C(ipso)
      C(ethynyl) bonds in p-diethynylbenzene are 0.001-0.002 A shorter than the
      corresponding bonds in ethynylbenzene and s-triethynylbenzene. This small effect
      is attributed to conjugation of the two substituents through the benzene ring.
      Comparison of experimental and MO results shows that the differences between the
      lengths of the C(ipso)-C(ethynyl) and C(ipso)-C(ortho) bonds in the three
      molecules, 0.023-0.027 A, are correctly computed at the MP2 and B3LYP levels of
      theory but are overestimated by a factor of 2 when calculated at the HF level.

PMID- 16451042
TI  - Molecular structures and compositions of trans-1,2-dichlorocyclohexane and trans
      1,2-difluorocyclohexane in the gas phase: an electron-diffraction investigation.
AB  - The structures and compositions of gaseous trans-1,2-dichloro- (DCCH) and trans
      1,2-difluorocyclohexane (DFCH), each of which may exist with the halogen atoms in
      a diaxial (aa) or diequatorial (ee) conformation, have been investigated by
      electron diffraction. The analysis was aided by rotational constants from
      microwave spectroscopy for the ee form of DFCH and by ab initio and density
      functional theory molecular orbital calculations for all species. The skeletons
      of the molecules have similar parameter values, but for the Cl-C-C-Cl and F-C-C-F
      fragments there are significant differences between the corresponding C-C-X bond
      angles and the X-C-C-X torsion angles in the two systems. There are also
      significant differences between the values of these parameters in the aa and ee
      forms of the same system. The composition of DCCH at 100 degrees C was measured
      to be 60(4)% aa, and that of DFCH at 70 degrees C was 42(7)% aa; the
      uncertainties are estimated 2sigma. From the preferred B3LYP/aug-cc-pVTZ
      calculations, the predicted theoretical composition is 51.2% aa for DCCH and
      40.8% aa for DFCH. (Calculations at the levels B3LYP/6-31G(d) and MP2/6-31G(d)
      give similar results for DCCH, but both predict more aa than ee for DFCH.) Values
      (r(g)/A and angle(alpha)/degree) for some of the more important parameters of the
      aa/ee forms of DCCH are <C-C> = 1.525(4)/1.525(6), C-Cl = 1.806(2)/1.787(2),
      angleC2-C1-Cl = 107.3(3)/111.5(3), angleC1-C2-C3 = 113.9(5)/111.6(5), angleC2-C3
      C4 = 111.3(12)/109.9(12), and Cl-C2-C3-Cl = 165.3(9)/-59.4(9); and for DFCH C-C =
      1.525(6)/1.520(9), C-F = 1.398(2)/1.390(2), angleC2-C1-F = 106.5(6)/109.2(6),
      angleC1-C2-C3 = 111.4(9)/110.9(9), angleC2-C3-C4 = 113.1(10)/113.1(10), and F-C2
      C3-F = 171.1(37)/-67.2(37). The structures and compositions are discussed.

PMID- 16451043
TI  - Impact of local and density fitting approximations on harmonic vibrational
      frequencies.
AB  - Harmonic vibrational frequencies are computed using second-order Moller-Plesset
      perturbation theory (MP2) with and without local (LMP2) and density fitting (DF)
      approximations. Results for a test set of 17 small and medium size molecules (366
      normal modes) are presented, and frequency scaling factors for LMP2 in
      combination with two different basis sets are determined. Comparison of the MP2
      and LMP2 frequencies with experimental data reveals that the introduction of
      local approximations leads to a slightly better agreement with experiment. This
      is attributed to the reduction of basis set superposition errors in local
      calculations. Introduction of DF approximations within the LMP2 formalism leads
      to negligible deviations but significantly reduces the computational cost. These
      facts extend the applicability of the method to larger systems with large basis
      sets. As an example, the method is applied to a full DF-LMP2/cc-pVTZ frequency
      calculation for testosterone (49 atoms).

PMID- 16451044
TI  - Origin of rotational barriers of the N-N bond in hydrazine: NBO analysis.
AB  - Hydrazine passes through two transition states, TS1 (phi = 0 degrees ) and TS2
      (phi = 180 degrees ), in the course of internal rotation around its N-N bond. The
      origin of the corresponding rotational barriers in hydrazine has been extensively
      studied by experimental and theoretical methods. Here, we used natural bond
      orbital (NBO) analysis and energy decomposition of rotational barrier energy
      (DeltaE(barrier)) to understand the origin of the torsional potential energy
      profile of this molecule. DeltaE(barrier) was dissected into structural
      (DeltaE(struc)), steric exchange (DeltaE(steric)), and hyperconjugative
      (DeltaE(deloc)) energy contributions. In both transition states, the major
      barrier-forming contribution is DeltaE(deloc). The TS2 barrier is lowered by
      pyramidalization of nitrogen atoms through lowering DeltaE(struc), not by N-N
      bond lengthening through lowering DeltaE(steric). Higher pyramidality of nitrogen
      atoms of TS2 than that of TS1 explains well why the N-N bond of TS2 is longer
      than that of TS1. Finally, the steric repulsion between nitrogen lone pairs does
      not determine the rotational barrier; nuclear-nuclear Coulombic repulsion between
      outer H/H atoms in TS1 plays an important role in increasing DeltaE(struc). Taken
      together, we explain the reason for the different TS1 and TS2 barriers. We show
      that NBO analysis is a useful tool for understanding structures and potential
      energy surfaces of compounds containing the N-N bond.

PMID- 16451045
TI  - Toward understanding the Hofmeister series. 3. Effects of sodium halides on the
      molecular organization of H2O as probed by 1-propanol.
AB  - We investigated the effects of NaF, NaCl, NaBr, and NaI on the molecular
      organization of H2O by a calorimetric methodology developed by us earlier. We use
      the third derivative quantities of G pertaining to 1-propanol (1P) in ternary 1P
      a salt-H2O as a probe to elucidate the effects of a salt on H2O. We found that
      NaF and NaCl worked as hydration centers. The hydration numbers were 19 +/- 2 for
      NaF and 7.5 +/- 0.6 for NaCl. Furthermore, the bulk H2O away from the hydration
      shell was found unaffected by the presence of Na+, F-, and Cl-. For NaBr and NaI,
      in addition to the hydration to Na+, Br- and I- acted like a hydrophilic moiety
      such as urea. Namely, they formed a hydrogen bond to the existing H2O network and
      retarded the fluctuation nature of H2O. These findings were discussed with
      respect to the Hofmeister ranking. We suggested that more chaotropic anions Br-
      and I- are characterized as hydrophiles, whereas kosmotropes, F- and Cl-, are
      hydration centers.

PMID- 16451046
TI  - Comment on "Temperature and pressure dependence of the multichannel rate
      coefficients for the CH3 + OH system".

PMID- 16451048
TI  - Aminoethylenes: a tetrahedral intermediate isostere yielding potent inhibitors of
      the aspartyl protease BACE-1.
AB  - A series of novel beta-site amyloid precursor protein cleaving enzyme (BACE-1)
      inhibitors containing an aminoethylene (AE) tetrahedral intermediate isostere
      were synthesized and evaluated in comparison to corresponding hydroxyethylene
      (HE) compounds. Enzymatic inhibitory values were similar for both isosteres, as
      were structure-activity relationships with respect to stereochemical preference
      and substituent variation (P2/P3, P1, and P2'); however, the AE compounds were
      markedly more potent in a cell-based assay for reduction of beta-secretase
      activity. The incorporation of preferred P2/P3, P1, and P2' substituents into the
      AE pharmacophore yielded compound 7, which possessed enzymatic and cell assay
      IC(50)s of 26 nM and 180 nM, respectively. A three-dimensional crystal structure
      of 7 in complex with BACE-1 revealed that the amino group of the inhibitor core
      engages the catalytic aspartates in a manner analogous to hydroxyl groups in HE
      inhibitors. The AE isostere class represents a promising advance in the
      development of BACE-1 inhibitors.

PMID- 16451049
TI  - A selective estrogen receptor modulator for the treatment of hot flushes.
AB  - A selective estrogen receptor modulator (SERM) for the potential treatment of hot
      flushes is described. (R)-(+)-7,9-difluoro-5-[4-(2-piperidin-1-ylethoxy)phenyl]
      5H-6-oxachrysen-2-ol, LSN2120310, potently binds ERalpha and ERbeta and is an
      antagonist in MCF-7 breast adenocarcinoma and Ishikawa uterine cancer cell lines.
      The compound is a potent estrogen antagonist in the rat uterus. In ovariectomized
      rats, the compound lowers cholesterol, maintains bone mineral density, and is
      efficacious in a morphine dependent rat model of hot flush efficacy.

PMID- 16451050
TI  - Identification of a novel spiropiperidine opioid receptor-like 1 antagonist class
      by a focused library approach featuring 3D-pharmacophore similarity.
AB  - A focused library approach identifying novel leads to develop a potent ORL1
      antagonist is described. Beginning from a compound identified by random
      screening, an exploratory library that exhibited a diverse display of
      pharmacophores was designed. After evaluating ORL1 antagonistic activity, a
      highly focused library was designed based on 3D-pharmacophore similarity to known
      actives. A novel D-proline amide class was identified in this library and was
      found to possess potent ORL1 antagonistic activity.

PMID- 16451052
TI  - Synthesis of thieno[2,3-b]pyridinones acting as cytoprotectants and as inhibitors
      of [3H]glycine binding to the N-methyl-D-aspartate (NMDA) receptor.
AB  - The standard glycine site antagonist of the N-methyl-D-aspartate (NMDA) receptor,
      3-phenyl-4-hydroxyquinolin-2(1H)-one (21), was used as a template for bioisostere
      benzene/thiophene exchange. Phenylacetylation of aminothiophene carboxylic acid
      methyl esters and subsequent cyclization delivered the three possible
      thienopyridinone isomers. 4-Hydroxy-5-phenylthieno[2,3-b]pyridin-6(7H)-one (3a),
      with the shortest distance between the sulfur and the nitrogen atom, was the most
      potent isomer (K(i) against the binding of [(3)H]glycine to rat membranes 16
      microM), comparable in potency to the model quinolinone (21, 12 microM).
      Replacement of the phenyl substituent of 21 by a 2-thienyl residue resulted in a
      2-5-fold loss in potency and was abandoned. In the thieno part of the
      thienopyridinone nucleus, the most successful substituents were halogen (Cl or
      Br) close to the sulfur atom and short alkyl chains at the other position,
      resulting in 7h, 8h, 8i, and 8m, with K(i) values between 5.8 and 10.5 nM.
      Introduction of a 3'-phenoxy moiety yielded several compounds with still higher
      potencies (18h, 18i, 18l, and 18m; K(i) between 1.1 and 2.0 nM). Quantitative
      structure-activity relationship (QSAR) calculations resulted in a consistent
      interpretation of the potencies of most compounds. Several of these 3'-phenoxy
      derivatives protected mouse fibroblast cell lines with transfected NMDA receptors
      from glutamate-induced toxicity. In addition, we report in vivo results for four
      of these compounds.

PMID- 16451051
TI  - Novel benzodiazepine photoaffinity probe stereoselectively labels a site deep
      within the membrane-spanning domain of the cholecystokinin receptor.
AB  - An understanding of the molecular basis of drug action provides opportunities for
      refinement of drug properties and for development of more potent and selective
      molecules that act at the same biological target. In this work, we have
      identified the active enantiomers in racemic mixtures of structurally related
      benzophenone derivatives of 1,5-benzodiazepines, representing both antagonist and
      agonist ligands of the type A cholecystokinin receptor. The parent compounds of
      the 1,5-benzodiazepine CCK receptor photoaffinity ligands were originally
      prepared in an effort to develop orally active drugs. The enantiomeric compounds
      reported in this study selectively photoaffinity-labeled the CCK receptor,
      resulting in the identification of a site of attachment for the photolabile
      moiety of the antagonist probe deep within the receptor's membrane-spanning
      region at Leu(88), a residue within transmembrane segment two. In contrast, the
      agonist probe labeled a region including extracellular loop one and a portion of
      transmembrane segment three. The antagonist covalent attachment site to the
      receptor served as a guide in the construction of theoretical three-dimensional
      molecular models for the antagonist-receptor complex. These models provided a
      means for visualization of physically plausible ligand-receptor interactions in
      the context of all currently available biological data that address small
      molecule interactions with the CCK receptor. Our approach, featuring the use of
      novel photolabile compounds targeting the membrane-spanning receptor domain to
      probe the binding site region, introduces powerful tools and a strategy for
      direct and selective investigation of nonpeptidyl ligand binding to peptide
      receptors.

PMID- 16451053
TI  - Synthesis and activity of 1,3,5-triphenylimidazolidine-2,4-diones and 1,3,5
      triphenyl-2-thioxoimidazolidin-4-ones: characterization of new CB1 cannabinoid
      receptor inverse agonists/antagonists.
AB  - Obesity and metabolic syndrome, along with drug dependence (nicotine, alcohol,
      opiates), are two of the major therapeutic applications for CB(1) cannabinoid
      receptor antagonists and inverse agonists. In the present study, we report the
      synthesis and structure-affinity relationships of 1,5-diphenylimidazolidine-2,4
      dione and 1,3,5-triphenylimidazolidine-2,4-dione derivatives. These new 1,3,5
      triphenylimidazolidine-2,4-dione derivatives and their thio isosteres were
      obtained by an original pathway and exhibited interesting affinity and
      selectivity for the human CB(1) cannabinoid receptor. A [(35)S]-GTPgammaS binding
      assay revealed the inverse agonist properties of the compounds at the CB(1)
      cannabinoid receptor. Furthermore, molecular modeling studies were conducted in
      order to delineate the binding mode of this series of derivatives into the CB(1)
      cannabinoid receptor. 1,3-Bis(4-bromophenyl)-5-phenylimidazolidine-2,4-dione (25)
      and 1,3-bis(4-chlorophenyl)-5-phenylimidazolidine-2,4-dione (23) are the
      imidazolidine-2,4-dione derivatives possessing the highest affinity for the human
      CB(1) cannabinoid receptor reported to date.

PMID- 16451054
TI  - Soft quaternary anticholinergics: comprehensive quantitative structure-activity
      relationship (QSAR) with a linearized biexponential (LinBiExp) model.
AB  - A comprehensive quantitative structure-activity relationship (QSAR) study is
      presented for quaternary soft anticholinergics including two distinctly different
      classes designed on the basis of the soft analogue and the inactive metabolite
      approaches. Because of the clear biphasic (bilinear) nature of the activity data
      when all structures (n = 76) were considered as a function of molecular size
      (volume), a nonlinear model had to be used, and a linearized biexponential
      (LinBiExp) model proved very adequate. LinBiExp can fit activity data that show a
      maximum (or a minimum) around a given parameter value but tend to show linearity
      away from this turning point. Contrary to Hansch-type parabolic models, LinBiExp
      represents a natural extension of linear models, and a direct correspondence
      between its parameters and those obtained earlier by linear regression on
      compound subsets covering more limited parameter ranges could be easily
      established. Stereospecificity was confirmed as important, and the presence of an
      acid moiety was found to essentially eliminate activity. The consideration of
      bilinear behavior, which most likely results from size limitations at the binding
      site, can also explain the embarrassingly low activity found for a relatively
      large compound predicted as highly active by Lien, Ariens, and co-workers based
      on their QSAR study.

PMID- 16451055
TI  - Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically
      with posaconazole.
AB  - There is no effective treatment for the prevalent chronic form of Chagas' disease
      in Latin America. Its causative agent, the protozoan parasite Trypanosoma cruzi,
      has an essential requirement for ergosterol, and ergosterol biosynthesis
      inhibitors, such as the antifungal drug posaconazole, have potent trypanocidal
      activity. The antiarrhythmic compound amiodarone, frequently prescribed for the
      symptomatic treatment of Chagas' disease patients, has also recently been shown
      to have antifungal activity. We now show here for the first time that amiodarone
      has direct activity against T. cruzi, both in vitro and in vivo, and that it acts
      synergistically with posaconazole. We found that amiodarone, in addition to
      disrupting the parasites' Ca(2+) homeostasis, also blocks ergosterol
      biosynthesis, and that posaconazole also affects Ca(2+) homeostasis. These
      results provide logical explanations for the synergistic activity of amiodarone
      with azoles against T. cruzi and open up the possibility of novel, combination
      therapy approaches to the treatment of Chagas' disease using currently approved
      drugs.

PMID- 16451056
TI  - Structure-based design, synthesis, and biological evaluation of novel inhibitors
      of human cyclophilin A.
AB  - Cyclophilin A is involved in many cellular processes, including protein folding
      and intracellular transports. Because cyclophilin A has been shown to interact
      with HIV-1 gag proteins and to enhance the viral infectivity,
      nonimmunosuppressive cyclophilin A ligands may represent a new class of
      therapeutic agents against HIV. Here, we report a virtual screening using
      structure- and pharmacophore-based design to identify original nonpeptidic
      cyclophilin ligands. Following a lead identification of compounds 1 [1-(3
      benzyloxypyridin-2-yl)-3-(3-chlorophenyl)urea] and 2 [1-(3-benzyloxypyridin-2-yl)
      3-(3-trifluoromethylphenyl)urea] (IC(50) = 0.3 microM), a series of molecules
      were synthesized from a diarylurea scaffold and evaluated for their in vitro
      ability to inhibit the cis-trans isomerase activity of cyclophilin A. Molecular
      modifications provided several more potent compounds, in particular analogues 4d
      and 4i with IC(50) of 14 and 20 nM, respectively. Then, we evaluated the effect
      of analogues 1 and 2 on HIV virion infectivity in both immortalized and primary
      cells. Both 1 and 2 reduced virion infectivity in the replication-defective one
      round infection assay, but only 1 impaired wild-type HIV infection in human
      peripheral blood mononuclear cells.

PMID- 16451057
TI  - Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic
      pocket formed by I3.28(125), I3.32(129), and I7.42(291) is critical for receptor
      activation.
AB  - The melanocortin 4 receptor is involved in the control of the feeding behavior
      and energy homeostasis. It is regulated by internal agonist (alpha-MSH) and
      antagonists (Agouti). Peptide agonists bind in a beta-turn conformation that
      organizes the characteristic message sequence (His-L/DPhe-Arg-Trp) in an optimal
      arrangement for binding and activation of the receptor. Our goal is to determine
      the most likely binding modes of peptide and small molecule agonists to use this
      information to guide our structure-based drug design efforts. Previous studies
      have identified some residues that are likely to be involved in peptide agonist
      binding, giving an initial estimate of the main contacts between peptides and
      receptor. However, a more detailed description of the orientation of the peptide
      in a beta-turn conformation in the binding site, as well as of the small molecule
      agonists, and it is commonalities with the peptide agonist binding modes is
      necessary to serve as the basis for structure-based drug design. In the current
      study we combine site-directed mutagenesis with molecular modeling studies to
      determine the most likely binding mode of peptide and small molecule agonists,
      and we found that Y6.58(268), Y7.38(287), I3.28(125), I3.32(129), and I7.42(291)
      also line the binding site and are likely to have direct contacts with the MC4R
      agonists. Of particular interest are residues I3.28(125), I3.32(129), and
      I7.42(291), which form a hydrophobic pocket where I7.42(291), on top of the NPXXY
      motif, is likely to act as a new rotamer switch implicated in the activation of
      the receptor.

PMID- 16451058
TI  - Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric
      sulfonamide phosphonates.
AB  - Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of
      zinc proteases that can degrade all the components of the extracellular matrix,
      could be useful for treatment of diseases such as cancer and arthritis. The most
      potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha
      Arylsulfonylamino phosphonates incorporate a particularly favorable combination
      of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity
      exceptionally attains the nanomolar strength frequently observed for hydroxamate
      analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4
      sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal
      structures of the complexes that the R- and S-enantiomers respectively form with
      MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are
      underlined and the differences in the mode of binding of analogous alpha
      arylsulfonylamino hydroxamates and carboxylates are discussed.

PMID- 16451059
TI  - Discovery of a daunorubicin analogue that exhibits potent antitumor activity and
      overcomes P-gp-mediated drug resistance.
AB  - Anthracyclines are considered to be some of the most effective anticancer drugs
      for cancer therapy. However, drug resistance and cardiotoxicity of anthracyclines
      limit their clinical application. We hypothesize that direct modifications of the
      sugar moiety of anthracyclines avert P-glycoprotein (P-gp) recognition and
      efflux, increase drug intracellular concentration in cancer cells, and thus
      overcome P-gp-mediated drug resistance. Daunorubicin (DNR) analogues with sugar
      modifications were synthesized by directly transforming the amino group of DNR to
      an azido group or triazole group. Molecular docking showed that the lead compound
      (3'-azidodaunorubicin, ADNR) averts P-gp binding, while daunorubicin (DNR)
      extensively interacts with multidrug-resistance (MDR) protein through H-bonds and
      electrostatic interactions. FACS assay demonstrated that these new compounds
      abolished P-gp drug efflux and accumulated high intracellular concentration in
      the drug-resistant leukemia K562/Dox. P-gp inhibition by CsA confirmed that these
      new analogues are no longer P-gp substrates. ADNR exhibited potent anticancer
      activity in both drug-sensitive (K562) and drug-resistant leukemia cells
      (K562/Dox), with a 25-fold lower drug resistance index than DNR. An in vivo
      xenograft model demonstrated that ADNR showed more than 2.5-fold higher maximum
      growth inhibition rate against drug-resistant cancers and significant improvement
      for animal survival rate versus DNR. No significant body weight reduction in mice
      was observed for ADNR at the maximum tolerable dose, as compared to more than 70%
      body weight reduction for DNR. These data suggest that sugar modifications of
      anthracyclines avert P-gp binding, abolish P-gp-mediated drug efflux, increase
      intracellular drug concentration, and thus overcome P-gp-mediated drug resistance
      in cancer therapy.

PMID- 16451060
TI  - Evaluation of carbon-11-labeled 2beta-carbomethoxy-3beta-[4'-((Z)-2
      iodoethenyl)phenyl]nortropane as a potential radioligand for imaging the
      serotonin transporter by PET.
AB  - The nortropane cocaine analogue, 2beta-carbomethoxy-3beta-[4'-((Z)-2
      iodoethenyl)phenyl]nortropane (ZIENT), is a high affinity, selective serotonin
      transporter (SERT) ligand that has shown promise as a SERT imaging agent for
      single photon computed tomography (SPECT) when labeled with I-123. Synthesis of
      the labeling precursor, radiosynthesis of [(11)C]ZIENT, and in vivo evaluation in
      anesthetized and awake monkeys have been performed to determine the suitability
      of [(11)C]ZIENT as a PET agent for SERT imaging.

PMID- 16451061
TI  - New arylthioindoles: potent inhibitors of tubulin polymerization. 2. Structure
      activity relationships and molecular modeling studies.
AB  - Arylthioindoles (ATIs) that possess a 3-methoxyphenylthio or a 3,5
      dimethoxyphenylthio moiety at position 2 of the indole ring were effective
      tubulin assembly inhibitors, but weak inhibitors of MCF-7 cell growth. ATIs
      bearing a 3-(3,4,5-trimethoxyphenyl)thio moiety were potent tubulin
      polymerization inhibitors, with IC(50)s in the 2.0 (35) to 4.5 (37) microM range.
      They also inhibited MCF-7 cell growth at nanomolar concentrations. The 3,4,5
      trimethoxy substituted ATIs showed potencies comparable to those of the reference
      compounds colchicine and combretastatin A-4 in both tubulin assembly and cell
      growth inhibition assays. Dynamics simulation studies correlate well with the
      observed experimental data. Furthermore, from careful analysis of the biological
      and in silico data, we can now hypothesize a basic pharmacophore for this class
      of compounds.

PMID- 16451062
TI  - Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B
      kinase inhibitors.
AB  - The synthesis of a novel series of quinazolines substituted at C4 by five
      membered ring aminoheterocycles is reported. Their in vitro structure-activity
      relationships versus Aurora A and B serine-threonine kinases is discussed. Our
      results demonstrate that quinazolines with a substituted aminothiazole at C4
      possess potent Aurora A and B inhibitory activity and excellent selectivity
      against a panel of various serine-threonine and tyrosine kinases, as exemplified
      by compound 46. We found also that the position and nature of the substituent on
      the thiazole play key roles in cellular potency. Compounds with an acetanilide
      substituent at C5' have the greatest cellular activity. The importance of the C5'
      position for substitution has been rationalized by ab initio molecular orbital
      calculations. Results show that the planar conformation with the sulfur of the
      thiazole next to the quinazoline N-3 is strongly favored over the other possible
      planar conformation. Compound 46 is a potent suppressor of the expression of
      phospho-histone H3 in tumor cells in vitro as well as in vivo, where 46,
      administered as its phosphate prodrug 54, suppresses the expression of phospho
      histone H3 in subcutaneously implanted tumors in nude mice.

PMID- 16451063
TI  - 3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones,
      potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase.
AB  - Recently, we disclosed a new class of HCV polymerase inhibitors discovered
      through high-throughput screening (HTS) of the GlaxoSmithKline proprietary
      compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4
      benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV
      polymerase enzymatic activity and inhibits the ability of the subgenomic HCV
      replicon to replicate in Huh-7 cells. This report will focus on the structure
      activity relationships (SAR) of substituents on the quinolinone ring, culminating
      in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin
      3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent
      potency in biochemical and cellular assays possessing attractive molecular
      properties for advancement as a clinical candidate. The potential for development
      and safety assessment profile of compound 130 will also be discussed.

PMID- 16451064
TI  - Cannabinoid CB2/CB1 selectivity. Receptor modeling and automated docking
      analysis.
AB  - Three-dimensional models of the CB1 and CB2 cannabinoid receptors were
      constructed by means of a molecular modeling procedure, using the X-ray structure
      of bovine rhodopsin as the initial template, and taking into account the
      available site-directed mutagenesis data. The cannabinoid system was studied by
      means of docking techniques. An analysis of the interaction of WIN55212-2 with
      both receptors showed that CB2/CB1 selectivity is mainly determined by the
      interaction in the CB2 with the nonconserved residues S3.31 and F5.46, whose
      importance was suggested by site-directed mutagenesis data. We also carried out
      an automated docking of several ligands into the CB2 model, using the AUTODOCK
      3.0 program; the good correlation obtained between the estimated free energy
      binding and the experimental binding data confirmed our binding hypothesis and
      the reliability of the model.

PMID- 16451065
TI  - Novel potent hepatitis C virus NS3 serine protease inhibitors derived from
      proline-based macrocycles.
AB  - The hepatitis C virus (HCV) NS3 protease is essential for viral replication. It
      has been a target of choice for intensive drug discovery research. On the basis
      of an active pentapeptide inhibitor, 1, we envisioned that macrocyclization from
      the P2 proline to P3 capping could enhance binding to the backbone Ala156 residue
      and the S4 pocket. Thus, a number of P2 proline-based macrocyclic alpha-ketoamide
      inhibitors were prepared and investigated in an HCV NS3 serine protease
      continuous assay (K(i*)). The biological activity varied substantially depending
      on factors such as the ring size, number of amino acid residues, number of methyl
      substituents, type of heteroatom in the linker, P3 residue, and configuration at
      the proline C-4 center. The pentapeptide inhibitors were very potent, with the C
      terminal acids and amides being the most active ones (24, K(i*) = 8 nM). The
      tetrapeptides and tripeptides were less potent. Sixteen- and seventeen-membered
      macrocyclic compounds were equally potent, while fifteen-membered analogues were
      slightly less active. gem-Dimethyl substituents at the linker improved the
      potency of all inhibitors (the best compound was 45, K(i*) = 6 nM). The
      combination of tert-leucine at P3 and dimethyl substituents at the linker in
      compound 47 realized a selectivity of 307 against human neutrophil elastase.
      Compound 45 had an IC(50) of 130 nM in a cellular replicon assay, while IC(50)
      for 24 was 400 nM. Several compounds had excellent subcutaneous AUC and
      bioavailability in rats. Although tripeptide compound 40 was 97% orally
      bioavailable, larger pentapeptides generally had low oral bioavailability. The X
      ray crystal structure of compounds 24 and 45 bound to the protease demonstrated
      the close interaction of the macrocycle with the Ala156 methyl group and S4
      pocket. The strategy of macrocyclization has been proved to be successful in
      improving potency (>20-fold greater than that of 1) and in structural
      depeptization.

PMID- 16451066
TI  - Design and synthesis of 5-aryl-pyridone-carboxamides as inhibitors of anaplastic
      lymphoma kinase.
AB  - Anaplastic lymphoma kinase (ALK) is a promising new target for therapy of certain
      cancers such as anaplastic large-cell lymphoma (ALCL) and inflammatory
      myofibroblastic tumor (IMT). We have identified a series of novel pyridones as
      kinase inhibitors of ALK by application of a stepwise process involving in vitro
      screening of a novel targeted library followed by iterative template modification
      based on medicinal chemistry insights and computational ranking of virtual
      libraries. Using this process, we discovered ALK-selective inhibitors with
      improved potency and selectivity. Herein the details of the design process and
      synthesis of these novel pyridones, along with their enzymatic and cell-based
      activity, are discussed.

PMID- 16451067
TI  - Potent CYP19 (aromatase) 1-[(benzofuran-2-yl)(phenylmethyl)pyridine, -imidazole,
      and -triazole inhibitors: synthesis and biological evaluation.
AB  - The synthesis of a series of novel 1-[(benzofuran-2-yl)phenylmethyl]-pyridine, 
      imidazole, and -triazole derivatives is described. All the compounds were
      evaluated in vitro for inhibitory activity against aromatase (P450(AROM), CYP19),
      using human placental microsomes. The 6-methoxy- and 6-hydroxy-substituted
      benzofuran derivatives were shown to be potent CYP19 inhibitors (IC(50) = 0.01
      1.46 microM) with activity greater than that observed for the unsubstituted
      parent compounds and inhibitory activity comparable with or greater than the
      reference compound arimidex (IC(50) = 0.6 microM). Six of the benzofuran
      derivatives were subjected to in vitro cytotoxicity assays, using rat liver
      hepatocytes with cytotoxicity determined from alteration in cell morphology and
      lactate dehydrogenase enzyme retention over a period of 24 h, and selectivity
      (CYP17, 17beta-HSD types 1 and 3, CYP24, and CYP26) determination; negligible
      inhibitory activity was observed, suggesting a good selectivity for CYP19. The
      pyridine benzofuran 4a containing the 4-fluorophenyl group was the most promising
      (IC(50) = 44 nM; LC(50) >100 microM) compared with arimidex (IC(50) = 600 nM;
      LC(50) > 200 microM).

PMID- 16451068
TI  - Docking of aminoglycosides to hydrated and flexible RNA.
AB  - Although much effort has been devoted to the development of programs suited for
      the docking of ligands to proteins, much less progress has been achieved in the
      nucleic acid field. We have developed a unique approach for docking
      aminoglycosides to RNA considering the flexibility of these macromolecules using
      conformational ensembles and accounting for the role of the first hydration
      shell. This concept, successfully implemented in AutoDock, relies on the
      computation of the intermolecular interaction energy that accounts for the
      presence of dynamically bound water molecules to the RNA. As an application, a
      set of 11 aminoglycosides was docked with an average root-mean-square deviation
      (RMSD) of 1.41 A to be compared with an average RMSD of 3.25 A when the original
      AutoDock protocol was used.

PMID- 16451069
TI  - SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA
      polymerase.
AB  - Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub
      micromolar biochemical potency have been identified which are selective for the
      inhibition of HCV NS5b over other polymerases. The structures of the complexes
      formed between several of these inhibitors and HCV NS5b were determined by X-ray
      crystallography, and the inhibitors were found to bind in an allosteric binding
      site separate from the active site. Structure-activity relationships and
      structural studies have identified the mechanism of action for compounds in this
      series, several of which possess drug-like properties, as unique, reversible,
      covalent inhibitors of HCV NS5b.

PMID- 16451070
TI  - GIP(Lys16PAL) and GIP(Lys37PAL): novel long-acting acylated analogues of glucose
      dependent insulinotropic polypeptide with improved antidiabetic potential.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin
      releasing peptide. We have developed two novel fatty acid derivatized GIP
      analogues, which bind to serum albumin and demonstrate enhanced duration of
      action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl
      peptidase IV (DPP IV) degradation. In vitro studies demonstrated that GIP
      analogues retained their ability to activate the GIP receptor through production
      of cAMP and to stimulate insulin secretion. Intraperitoneal administration of GIP
      analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic
      excursion and elicited increased and prolonged insulin responses compared to
      native GIP. A protracted glucose-lowering effect was observed 24 h following
      GIP(Lys(37)PAL) administration. Once a day injection for 14 days decreased
      nonfasting glucose, improved glucose tolerance, and enhanced the insulin response
      to glucose. These data demonstrate that fatty acid derivatized GIP peptides
      represent a novel class of long-acting stable GIP analogues for therapy of type 2
      diabetes.

PMID- 16451071
TI  - Dual inhibitors of thymidylate synthase and dihydrofolate reductase as antitumor
      agents: design, synthesis, and biological evaluation of classical and
      nonclassical pyrrolo[2,3-d]pyrimidine antifolates(1).
AB  - We designed and synthesized a classical analogue N-[4-[(2-amino-6-ethyl-3,4
      dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)thio]benzoyl]-L-glutamic acid (4)
      and thirteen nonclassical analogues 5-17 as potential dual thymidylate synthase
      (TS) and dihydrofolate reductase (DHFR) inhibitors and as antitumor agents. The
      key intermediate in their synthesis was 2-amino-6-ethyl-3,4-dihydro-4-oxo-7H
      pyrrolo[2,3-d]pyrimidine, 22, to which various aryl thiols were conveniently
      attached at the 5-position via an oxidative addition reaction using iodine. For
      the classical analogue 4, the ester obtained from the reaction was deprotected
      and coupled with diethyl L-glutamate followed by saponification. Compound 4 was a
      potent dual inhibitor of human TS (IC(50) = 90 nM) and human DHFR (IC(50) = 420
      nM). Compound 4 was not a substrate for human FPGS. Metabolite protection studies
      established TS as its principal target. Most of the nonclassical analogues were
      only inhibitors of human TS with IC(50) values of 0.23-26 microM.

PMID- 16451072
TI  - Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the design
      of potent inhibitors of cathepsin K.
AB  - A new series of nonpeptidic cathepsin K inhibitors that are based on a beta
      substituted cyclohexanecarboxamide motif has been developed. Lead optimization
      yielded compounds with sub-nanomolar potency and exceptional selectivity profiles
      against cathepsins B, L, and S. Use of fluorine atoms to block metabolism on the
      cyclohexyl ring led to compounds with excellent pharmacokinetic properties.
      Considering the well-established role of cathepsin K in osteoclast-mediated bone
      turnover, compounds such as (-)-34a (hrab Cat K IC(50) 0.28 nM; >800-fold
      selectivity vs Cat B, L, and S; PK data in dogs: F 55%, t(1/2) = 15 h) exhibit
      great potential for development as an orally bioavailable therapeutic for
      treatment of diseases that involve bone loss.

PMID- 16451073
TI  - Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol-4
      yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate
      receptor subtype 5 antagonists; search for cocaine medications.
AB  - Recent genetic and pharmacological studies have suggested that the metabotropic
      glutamate receptor subtype 5 (mGluR5) may represent a druggable target in
      identifying new therapeutics for the treatment of various central nervous system
      disorders including drug abuse. In particular, considerable attention in the
      mGluR5 field has been devoted to identifying ligands that bind to the allosteric
      modulatory site, distinct from the site for the primary agonist glutamate. Both 2
      methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4
      thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent
      noncompetitive antagonists of mGluR5. Because of results presented in this study
      showing that MTEP prevents the reinstatement of cocaine self-administration
      caused by the presentation of environmental cues previously associated with
      cocaine availability, we have prepared a series of analogues of MTEP with the aim
      of gaining a better understanding of the structural features relevant to its
      antagonist potency and with the ultimate aim of investigating the effects of such
      compounds in blunting the self-administration of cocaine. These efforts have led
      to the identification of compounds showing higher potency as mGluR5 antagonists
      than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity
      as mGluR5 antagonists that are 490 and 230 times, respectively, better than that
      of MTEP.

PMID- 16451074
TI  - Trace amine-associated receptor agonists: synthesis and evaluation of
      thyronamines and related analogues.
AB  - We have previously shown that several thyronamines, decarboxylated and
      deiodinated metabolites of the thyroid hormone, potently activate an orphan G
      protein-coupled receptor in vitro (TAAR1) and induced hypothermia in vivo on a
      rapid time scale [Scanlan, T. S.; Suchland, K. L.; Hart, M. E.; Chiellini, G.;
      Huang, Y.; Kruzich, P. J.; Frascarelli, S.; Crossley, D. A.; Bunzow, J. R.; Ronca
      Testoni, S.; Lin, E. T.; Hatton, D.; Zucchi, R.; Grandy, D. K. 3-Iodothyronamine
      is an endogenous and rapid-acting derivative of thyroid hormone. Nat. Med. 2004,
      10 (6), 638-642]. Herein, we report the synthesis of these thyronamines.
      Additionally, a large number of thyroamine derivatives were synthesized in an
      effort to understand the molecular basis of TAAR1 activation and hypothermia
      induction. Several derivatives were found to potently activate both rTAAR1 and
      mTAAR1 in vitro (compounds 77, 85, 91, and 92). When administered to mice at a 50
      mg/kg dose, these derivatives all induced significant hypothermia within 60 min
      and exhibited a hypothermic induction profile analogous to 3-iodothyronamine (1,
      T(1)AM) except 91, which proved to be more efficacious. On the basis of this
      result, a dose-dependent profile for 91 was generated and an ED(50) of 30
      mumol/kg was calculated. Compound 91 proved to be more potent than T(1)AM for
      TAAR1 activation and exhibits increased potency and efficacy for hypothermia
      induction. These data further strengthen the pharmacological correlation linking
      TAAR1 activation by thyronamines and hypothermia induction in mice.

PMID- 16451076
TI  - Probabilistic neural network model for the in silico evaluation of anti-HIV
      activity and mechanism of action.
AB  - A theoretical model has been developed that discriminates between active and
      nonactive drugs against HIV-1 with four different mechanisms of action for the
      active drugs. The model was built up using a probabilistic neural network (PNN)
      algorithm and a database of 2720 compounds. The model showed an overall accuracy
      of 97.34% in the training series, 85.12% in the selection series, and 84.78% in
      an external prediction series. The model not only correctly classified a very
      heterogeneous series of organic compounds but also discriminated between very
      similar active/nonactive chemicals that belong to the same family of compounds.
      More specifically, the model recognized 96.02% of nonactive compounds, 94.24% of
      active compounds that inhibited reverse transcriptase, 97.24% of protease
      inhibitors, 97.14% of virus uncoating inhibitors, and 90.32% of integrase
      inhibitors. The results indicate that this approach may represent a powerful tool
      for modeling large databases in QSAR with applications in medicinal chemistry.

PMID- 16451075
TI  - New cannabidiol derivatives: synthesis, binding to cannabinoid receptor, and
      evaluation of their antiinflammatory activity.
AB  - Cannabidiol (CBD) and cannabidiol dimethyl hephtyl (CBD-DMH) were hydrogenated to
      give four different epimers. The new derivatives were evaluated for their ability
      to modulate the production of reactive oxygen intermediates (ROI), nitric oxide
      (NO), and tumor necrosis factor (TNF-alpha) by murine macrophages, and for their
      binding to the cannabinoid receptor (CB(1)). Surprisingly, we found that these
      derivatives exhibit good binding to CB(1). In addition hydrogenated CBD and CBD
      DMH demonstrate bioactivities different from their original compounds.

PMID- 16451078
TI  - Synthesis of cyclopentenyl carbocyclic nucleosides as potential antiviral agents
      against orthopoxviruses and SARS.
AB  - A practical and convenient methodology for the synthesis of chiral cyclopentenol
      derivative (+)-12a has been developed as the key intermediate that was utilized
      for the synthesis of biologically active carbocyclic nucleosides. The selective
      protection of allylic hydroxyl group followed by the ring-closing metathesis
      (RCM) reaction with Grubbs catalysts provided (+)-12a on a 10 g scale with 52%
      overall yield from D-ribose (4). The key intermediate (+)-12a was utilized for
      the synthesis of unnatural five-membered ring heterocyclic carbocyclic
      nucleosides. The newly synthesized 1,2,3-triazole analogue (17c) exhibited potent
      antiviral activity (EC(50) 0.4 microM) against vaccinia virus and moderate
      activities (EC(50) 39 microM) against cowpox virus and severe acute respiratory
      syndrome coronavirus (SARSCoV) (EC(50) 47 microM). The 1,2,4-triazole analogue
      (17a) also exhibited moderate antiviral activity (EC(50) 21 microM) against
      SARSCoV.

PMID- 16451077
TI  - Pyrrolizidine esters and amides as 5-HT4 receptor agonists and antagonists.
AB  - A series of pyrrolizidine esters, amides, and ureas was prepared and tested for 5
      HT(4) and 5-HT(3) receptor binding, 5-HT(4) receptor agonism in the rat tunica
      muscularis mucosae (TMM) assay, and for 5-HT(3) receptor-mediated functional
      antagonism in the Bezold-Jarisch reflex assay. Several pyrrolizidine derivatives
      were identified with high affinity for the 5-HT(4) receptor, including benzamide
      12a (SC-53116), a potent and selective 5-HT(4) partial agonist that exhibits
      efficacy in promoting antral contractions and activity in promoting gastric
      emptying in canine models. Also discovered were 5-HT(4) receptor antagonists,
      including imidazopyridine amide 12h (SC-53606), which is a potent and selective 5
      HT(4) receptor antagonist with a pA(2) value of 8.13 in the rat TMM assay. N
      Methyl indole ester 13d was identified as a potent 5-HT(4) antagonist with a
      pA(2) value of 8.93. High selectivity was observed for these pyrrolizidine
      derivatives versus other monoamine receptors, including 5-HT(1), 5-HT(2), D(1),
      D(2), alpha(1), alpha(2), and beta receptors.

PMID- 16451079
TI  - A QSAR model for in silico screening of MAO-A inhibitors. Prediction, synthesis,
      and biological assay of novel coumarins.
AB  - This work explores the potential of the MARCH-INSIDE methodology to seek a QSAR
      for MAO-A inhibitors from a heterogeneous series of compounds. A Markov model was
      used to quickly calculate the molecular electron delocalization, polarizability,
      refractivity, and n-octanol/water partition coefficients for a series of 1406
      active/nonactive compounds. LDA was subsequently used to fit a classification
      function. The model showed 92.8% and 91.8% global accuracy and predictability in
      training and validation studies. This QSAR model was validated through a virtual
      screening of a series of coumarin derivatives. The 15 selected compounds were
      prepared and evaluated as in vitro MAO-A inhibitors. The theoretical prediction
      was compared with the experimental results and the model correctly predicted 13
      compounds with only two mistakes on compounds with activities very close to the
      cutoff point established for the model. Consequently, this method represents a
      useful tool for the "in silico" screening of MAO-A inhibitors.

PMID- 16451081
TI  - Discovery and structure-activity relationship of antagonists of B-cell lymphoma 2
      family proteins with chemopotentiation activity in vitro and in vivo.
AB  - Development of a rationally designed potentiator of cancer chemotherapy, via
      inhibition of Bcl-X(L) function, is described. Lead compounds generated by NMR
      screening and directed parallel synthesis displayed sub-microM binding but were
      strongly deactivated in the presence of serum. The dominant component of serum
      deactivation was identified as domain III of human serum albumin (HSA); NMR
      solution structures of inhibitors bound to both Bcl-X(L) and HSA domain III
      indicated two potential optimization sites for separation of affinities.
      Modifications at both sites resulted in compounds with improved Bcl-X(L) binding
      and greatly increased activity in the presence of human serum, culminating in
      73R, which bound to Bcl-X(L) with a K(i) of 0.8 nM. In a cellular assay 73R
      reversed the protection afforded by Bcl-X(L) overexpression against cytokine
      deprivation in FL5.12 cells with an EC(50) of 0.47 microM. 73R showed little
      effect on the viability of the human non small cell lung cancer cell line A549.
      However, consistent with the proposed mechanism, 73R potentiated the activity of
      paclitaxel and UV irradiation in vitro and potentiated the antitumor efficacy of
      paclitaxel in a mouse xenograft model.

PMID- 16451082
TI  - Mono- and polynuclear [alkylamine]platinum(II) complexes of [1,2-bis(4
      fluorophenyl)ethylenediamine]platinum(II): synthesis and investigations on
      cytotoxicity, cellular distribution, and DNA and protein binding.
AB  - A series of mononuclear and dinuclear alkylamine derivatives of [meso-1,2-bis(4
      fluorophenyl)ethylenediamine]platinum(II) (m-4F-PtL-R1 and (m-4F-PtL)2-R2; R(1) =
      alkylamine, R(2) = alkyldiamine, L = DMSO or Cl) as well as the DAB(PA)(4)
      polyimine dendrimer complex ((m-4F-PtDMSO)4DAB(PA)4; DAB(PA)4 = N,N,N',N'
      tetrakis(3-aminopropyl)butane-1,4-diamine) were synthesized and tested for
      cytotoxicity, intracellular distribution, and DNA and protein binding. All
      compounds strongly bound to human serum albumin by hydrophobic and electrostatic
      interactions. These inactivation reactions hindered the uptake into tumor cells
      and prevented strong cytotoxic effects. If serum-free medium was used, a high
      accumulation grade in MCF-7 breast cancer cells and a high DNA binding was
      observed. As most efficient compound (m-4F-PtDMSO)4DAB(PA)4 was identified. It
      showed a 20-fold higher cellular uptake and an approximately 700-fold higher DNA
      binding than cisplatin.

PMID- 16451080
TI  - PABA/NO as an anticancer lead: analogue synthesis, structure revision, solution
      chemistry, reactivity toward glutathione, and in vitro activity.
AB  - PABA/NO is a diazeniumdiolate of structure Me(2)NN(O)=NOAr (where Ar is a 5
      substituted-2,4-dinitrophenyl ring whose 5-substituent is N-methyl-p-aminobenzoic
      acid). It has shown activity against human ovarian cancer xenografts in mice
      rivaling that of cisplatin, but it is poorly soluble and relatively unstable in
      water. Here we report structure-based optimization efforts resulting in three
      analogues with improved solubility and stability in aqueous solution. We sought
      to explain PABA/NO's physicochemical uniqueness among these four compounds, whose
      aminobenzoic acid precursors differ structurally only in the presence or absence
      of the N-methyl group and/or the position of the carboxyl moiety (meta or para).
      Studies revealed that PABA/NO's N-methyl-p-aminobenzoic acid substituent is bound
      to the dinitrobenzene ring via its carboxyl oxygen while the other three are
      linked through the aniline nitrogen. This constitutes a revision of the
      previously published PABA/NO structure. All four analogues reacted with GSH to
      produce bioactive nitric oxide (NO), but PABA/NO was the most reactive.
      Consistent with PABA/NO's potent suppression of A2780 human ovarian cancer
      xenograft growth in mice, it was the most potent of the four in the OVCAR-3 cell
      line.

PMID- 16451083
TI  - Synthesis and biological evaluation of novel, peripherally selective chromanyl
      imidazolethione-based inhibitors of dopamine beta-hydroxylase.
AB  - A novel series of dopamine beta-hydroxylase (DBH) inhibitors was designed and
      synthesized incorporating modifications to the core structure of nepicastat 3,
      with the principal aim of discovering potent DBH inhibitors exerting minimal
      effects on dopamine (DA) and noradrenaline (NA) levels in the central nervous
      system. This study resulted in the identification of a potent, peripherally
      selective DBH inhibitor, (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3
      dihydroimidazole-2-thione hydrochloride 54 (BIA 5-453). In experiments in mice
      and rats at T(max) (9 h after administration), 54 reduced NA levels in a dose
      dependent manner in both the left atrium and the left ventricle, with the maximal
      inhibitory effect attained at a dose of 100 mg/kg. In contrast to that found in
      the heart, 54 failed to affect NA tissue levels in the brain. Compound 54 is thus
      presented as a candidate for clinical evaluation for the treatment of chronic
      heart failure and hypertension.

PMID- 16451084
TI  - Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent
      severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.
AB  - This paper describes the design and synthesis of dipeptidyl N,N-dimethyl
      glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome
      coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV
      induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting
      effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk
      (6a) was found to be a potent inhibitor with low toxicity in cells, protecting
      cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of
      >40.

PMID- 16451085
TI  - Design, synthesis, and biological activity of novel polycyclic aza-amide FKBP12
      ligands.
AB  - Since the discovery that FK-506 promotes neurite outgrowth, considerable
      attention has been focused on the development of potent nonimmunosuppressive
      ligands for FK-506 binding proteins (FKBPs). Such neuroimmunophilin agents have
      been reported to show neuroregenerative activity in a variety of cell and animal
      models including neurite outgrowth, age-related cognitive decline, Parkinson's
      disease, peripheral nerve injury, optic nerve degeneration, and diabetic
      neuropathy. We have designed and synthesized a unique series of tetracyclic aza
      amides that have been shown to be potent FKBP12 rotamase inhibitors. The
      structure-activity relationships established in this study have demonstrated
      diverse structural modifications that result in potent rotamase inhibitory
      activity.

PMID- 16451086
TI  - Evaluation of hydroxyimine as cytochrome P450-selective prodrug structure.
AB  - Hydroxyimine derivatives of ketoprofen (1) and nabumetone (2) were synthesized
      and evaluated in vitro and in vivo as cytochrome P450-selective intermediate
      prodrug structures of ketones. 2 released nabumetone in vitro in the presence of
      isolated rat and human liver microsomes and in different recombinant human CYP
      isoforms. Bioconversion of 2 to both nabumetone and its active metabolite, 6
      methoxy-2-naphthylacetic acid (6-MNA), was further confirmed in rats in vivo.
      Results indicate that hydroxyimine is a useful intermediate prodrug structure for
      ketone drugs.

PMID- 16451087
TI  - Indol-1-yl acetic acids as peroxisome proliferator-activated receptor agonists:
      design, synthesis, structural biology, and molecular docking studies.
AB  - A series of novel indole-based PPAR agonists is described leading to discovery of
      10k, a highly potent PPAR pan-agonist. The structural biology and molecular
      docking studies revealed that the distances between the acidic group and the
      linker, when a ligand was complexed with PPARgamma protein, were important for
      the potent activity. The hydrophobic tail part of 10k makes intensive hydrophobic
      interaction with the PPARgamma protein resulting in potent activity.

PMID- 16451088
TI  - Synthesis and cytotoxic evaluation of new derivatives of the marine alkaloid
      variolin B.
AB  - The marine alkaloid variolin B 2 and eight synthetic derivatives with different
      substituents at positions C-5 and C-7 have been tested in a panel of sixteen
      human tumor cell lines to evaluate their cytotoxic potential.

PMID- 16451089
TI  - Impact of increased heart rate on clinical outcomes in hypertension: implications
      for antihypertensive drug therapy.
AB  - Thirty-eight studies have been published to date on the association between
      elevated heart rate and mortality. After adjustment for other risk factors, only
      two studies for all-cause mortality and four studies for cardiovascular mortality
      reported an absence of association between heart rate and mortality in male
      populations. This relationship has been found to be generally weaker among
      females. Most of these studies investigated samples of general populations. The
      four studies performed in hypertensive men found a positive association between
      heart rate and all-cause mortality (hazard ratios ranging from 1.9 to 2.0) or
      cardiovascular mortality (hazard ratios ranging from 1.3 to 1.7). In spite of
      this evidence, elevated heart rate remains a neglected cardiovascular risk factor
      in both genders. The pathogenetic mechanisms connecting high heart rate,
      hypertension, atherosclerosis and cardiovascular events have also been explicated
      in many studies. Elevated heart rate is due to an increased sympathetic and
      decreased parasympathetic tone. This altered balance of the autonomic nervous
      system tone could explain the increase in events with the increased heart rate.
      However, it has also been proved that blood flow changes associated with high
      heart rate favour both the formation of the atherosclerotic lesion and the
      occurrence of the cardiovascular event. Reduction of heart rate in hypertensive
      patients with increased heart rate could be an additional goal of
      antihypertensive therapy. Several trials retrospectively showed the beneficial
      effect of cardiac-slowing drugs, such as beta-adrenoceptor antagonists (beta
      blockers) and non-dihydropyridine calcium channel antagonists, on mortality,
      notably in patients with coronary heart disease, but no published data are
      available in patients with hypertension free of coronary heart disease. Other
      antihypertensive drugs that have been shown to reduce the heart rate are
      centrally acting drugs and angiotensin II receptor antagonists, but their
      bradycardic effect is rather weak. The f-channel antagonist ivabradine is a
      selective heart rate-lowering agent with no effect on blood pressure. Although it
      has not been proven in existing trials, it would seem reasonable to recommend
      antihypertensive agents that decrease the heart rate in hypertensive patients
      with a heart rate higher than 80-85 beats per minute. Since the fast heart rate
      per se causes cardiovascular damage, all drugs that lower the heart rate have the
      potential of further reducing cardiovascular events in patients with elevated
      heart rate. Unfortunately, lowering of the heart rate is not a clinically
      recognised goal. Prospective trials investigating whether treatment of high heart
      rate can prevent cardiovascular events, notably in hypertensive patients, are
      warranted.

PMID- 16451090
TI  - HMG-CoA reductase inhibitors in chronic heart failure: potential mechanisms of
      benefit and risk.
AB  - HMG-CoA reductase inhibitors (statins) have been shown to reduce mortality and
      cardiovascular morbidity in patients with hyperlipidaemia and those with coronary
      artery disease. However, evidence for statin treatment in patients with chronic
      heart failure (CHF) remains a subject of debate. Patients with heart failure were
      generally excluded in the existing trials and a different patient population with
      a distinct pattern of morbidity and treatment was studied. In addition, no safety
      data are available for statins in patients with heart failure, where there are
      potential concerns about coenzyme Q10 depletion and excessive low-density
      lipoprotein reduction. This review summarises the clinical and preclinical
      evidence for potential beneficial effects of statins in CHF. In experimental
      systems, statins have been shown to improve cardiac function through
      antioxidative and anti-inflammatory action. Statins improve endothelial function,
      may reduce neurohormonal activation, and stimulate endothelial progenitor cells.
      Some of these effects occur independently of cholesterol lowering and can be
      explained by inhibition of isoprenylation of signal transducing proteins of the
      family of Rho guanosine triphosphatases. Two ongoing controlled randomised trials
      (CORONA [Controlled Rosuvastatin Multinational Study in Heart Failure] and GISSI
      HF [Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-
      Heart Failure]) will help us to assess whether the described beneficial effects
      of statins in heart failure outweigh the potential negative effects and translate
      into the reduction of clinical endpoints.

PMID- 16451092
TI  - Solifenacin in overactive bladder syndrome.
AB  - Overactive bladder (OAB) syndrome is a prevalent condition, increasingly
      recognised as a cause of reduced quality of life that places a substantial
      economic burden on healthcare provision. While antimuscarinic agents are the
      therapy of choice for OAB, their use is associated with a number of drawbacks,
      not least of which is the high rate of adverse events, which is intimately linked
      with poor compliance with treatment. Solifenacin succinate is a novel
      antimuscarinic agent approved in Europe and the US for the treatment of men and
      women with OAB. The recommended starting dose of solifenacin is 5 mg once daily
      and, if needed, the dose may be increased to 10 mg once daily. In multiple
      clinical trials, solifenacin treatment has been associated with statistically
      significant reductions in all key symptoms of OAB (notably frequency, urgency and
      incontinence) as well as increases in volume voided. Solifenacin has been shown
      to be well tolerated, producing few adverse effects, which are usually mild in
      nature. Furthermore, possibly because of this favourable efficacy and
      tolerability, solifenacin treatment has been associated with a high rate of
      patient persistence with therapy, with 81% of 1802 patients who completed 12
      week, double-blind trials enrolling in and completing a 40-week open-label
      extension study. Solifenacin has been shown to display selectivity for bladder
      versus salivary tissue in vitro, and studies in healthy men have shown that
      absorption is slow but extensive with an absolute bioavailability of 88%.
      Solifenacin is a well tolerated and efficacious agent for the treatment of OAB,
      significantly reducing symptoms and improving patients' quality of life.

PMID- 16451094
TI  - Tramadol sustained-release capsules.
AB  - Tramadol is a synthetic, centrally acting analgesic. A sustained-release (SR)
      capsule formulation of tramadol gradually releases active drug, allowing for
      twice-daily dosing. Compared with tramadol SR tablets, tramadol SR capsules
      produced a smoother plasma concentration profile, with more gradual absorption
      and lower peak concentrations. There was less intra- and intersubject variability
      in tramadol plasma concentrations with SR capsules versus SR. Tramadol SR
      capsules had identical bioavailability to tramadol immediate-release (IR)
      capsules with lower peak concentrations and less fluctuation in plasma
      concentrations. Tramadol SR 100 mg capsules administered twice daily had
      equivalent efficacy to tramadol IR 50 mg capsules administered four times daily
      in the treatment of moderate to severe chronic low back pain in a well designed
      study. Patients receiving tramadol SR capsules were significantly less likely
      than those receiving tramadol IR capsules to report nausea. Starting treatment
      with tramadol SR capsules at a dosage of 50 mg twice daily with subsequent dose
      escalation resulted in improved tolerability in patients with moderate to severe
      chronic pain. The lowest tramadol SR capsule dosage of 50 mg twice daily
      (administered to 35% of patients with moderate to severe non-oncological pain)
      significantly improved pain intensity and frequency in 83.4% and 70.4% of
      patients, respectively, in a postmarketing observational study evaluating
      tramadol SR capsules 50-200 mg twice daily (n = 3888).

PMID- 16451095
TI  - Tramadol sustained-release capsules : a viewpoint by Maurizio Evangelista.

PMID- 16451091
TI  - Psychiatric and substance use disorders in individuals with hepatitis C:
      epidemiology and management.
AB  - Hepatitis C virus (HCV) infection is a major health concern in the US as well as
      in other countries worldwide. Treatment issues and disease management strategies
      are complicated by the extremely high rate of psychiatric and substance use
      disorders in those who have HCV. The majority of new and existing cases of HCV
      are related to injection drug use and, in this population, the prevalence of
      psychiatric comorbidity is high. Optimally, all patients with HCV should be
      screened for psychiatric and substance use disorders before initiation of
      antiviral therapy. If a patient screens positive, he or she should be referred to
      a mental healthcare provider or addiction specialist, assessed for the presence
      of a psychiatric or substance use disorder, and appropriately treated prior to
      initiation of antiviral (i.e. interferon) therapy. Although interferon-based
      therapies can lead to severe neuropsychiatric adverse effects, including in rare
      instances suicide, evidence suggests that many patients with comorbid psychiatric
      and substance use diagnoses can be treated safely and effectively using
      comanagement strategies. However, most patients with HCV are not treated with
      antiviral therapy. Therefore, we must expand our definition of HCV 'treatment' to
      include treatment of the comorbid psychiatric and substance use disorders that
      accompany HCV infection and precede antiviral therapy. This paper reviews the
      epidemiology and management of psychiatric and substance use disorders in
      patients with HCV, the issue of psychiatric and substance use disorders as
      contraindications for antiviral therapy, and current treatment strategies for HCV
      patients with these comorbid conditions.

PMID- 16451096
TI  - Tramadol sustained-release capsules: a viewpoint by Miquel Casals.

PMID- 16451097
TI  - Tramadol sustained-release capsules : a viewpoint by Sergio Canavero and Vincenzo
      Bonicalzi.

PMID- 16451093
TI  - Emerging selective estrogen receptor modulators: special focus on effects on
      coronary heart disease in postmenopausal women.
AB  - Menopause, regardless of age at onset, is associated with a marked increase in
      coronary heart disease (CHD) risk. On the basis of epidemiological studies that
      demonstrated mainly positive effects of postmenopausal hormone therapy on CHD as
      well as on risk markers of CHD, it has been suggested that CHD could be prevented
      in postmenopausal women with long-term hormone therapy. However, since the
      publications of the Heart and Estrogen/progestin Replacement Study and the
      Women's Health Initiative trial, prescription of hormone therapy for the
      prevention of CHD has become controversial. Major efforts have been made to
      identify alternatives for hormone therapy. Compounds suggested have included
      selective estrogen receptor modulators (SERMs), which represent a class with a
      growing number of compounds that act as either estrogen receptor agonists or
      antagonists in a tissue-specific manner. This pharmacological profile may offer
      the opportunity to dissociate favourable estrogenic effects on the bone and
      cardiovascular system from unfavourable stimulatory effects on the breast and
      endometrium. Two SERMs presently on the market are tamoxifen and raloxifene. The
      only data available regarding the effects of tamoxifen on cardiovascular events
      in postmenopausal women are from breast cancer trials. These trials found fewer
      fatal myocardial events in women randomly assigned to tamoxifen compared with
      women assigned to placebo. Raloxifene is a second-generation SERM that has been
      shown to prevent osteoporotic fractures, is safe for the endometrium and holds
      high promise for the prevention of breast cancer. The effect of raloxifene on CHD
      is still uncertain. On the basis of the MORE (Multiple Outcomes of Raloxifene
      Evaluation) trial, raloxifene may offer some protection to women with CHD or to
      those who are at high risk of CHD. Proof that raloxifene reduces the risk of CHD
      requires a clinical trial with hard clinical endpoints. Such a study is currently
      underway. Next-generation SERMs taken into clinical development include
      idoxifene, droloxifene, ospemifene, arzoxifene, acolbifene/EM-800,
      levormeloxifene, lasofoxifene, bazedoxifene and HMR 3339. The aim is to find a
      compound with the ideal profile, that is, alleviation of climacteric symptoms and
      prevention of osteoporotic fractures, but without an adverse effect on the breast
      and endometrium, and no negative effect or even a beneficial effect on the
      cardiovascular system and the brain. Currently, limited data are available with
      regard to these next-generation SERMs and CHD. Nevertheless, some of these novel
      agents provide arguments for continuing the search for an ideal SERM.

PMID- 16451098
TI  - Perindopril: a review of its use in patients with or at risk of developing
      coronary artery disease.
AB  - Perindopril (Coversyl) is a prodrug ester of perindoprilat, an ACE inhibitor.
      This agent has shown pharmacodynamic effects beyond those responsible for
      lowering blood pressure (BP), including the improvement of endothelial function
      and the normalisation of vascular and cardiac structure and function. Perindopril
      has a well established role in the treatment of patients with hypertension or
      heart failure. In the EUROPA trial, once-daily perindopril 8 mg prevented
      cardiovascular events in patients with stable coronary artery disease (CAD)
      without any apparent heart failure receiving standard recommended therapy. In the
      ASCOT-BPLA trial, a calcium channel antagonist +/- perindopril regimen
      demonstrated significant cardiovascular benefits compared with a conventional
      beta-blocker +/- diuretic regimen in patients with hypertension who were at risk
      of developing cardiovascular events. These trials demonstrate that while
      perindopril, in addition to standard recommended therapy, has a potential role in
      preventing cardiovascular events in hypertensive patients, its role in the
      management of patients with stable CAD is clearly established.

PMID- 16451100
TI  - Immunotherapy and the development of cancer vaccines.

PMID- 16451103
TI  - Development of the PANVAC-VF vaccine for pancreatic cancer.
AB  - PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia
      virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic
      antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include
      B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen
      3. Vaccination is administered by subcutaneous injection followed by 4 days of
      local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at
      the vaccination site. The vaccine has been developed for patients with advanced
      pancreatic cancer and has now entered a randomized Phase III clinical trial. This
      review will describe the background of recombinant poxvirus technology for tumor
      vaccine development, detail the key preclinical studies supporting the regimen,
      review the clinical trials supporting the current Phase III study, and highlight
      the key challenges and future obstacles to successful implementation of PANVAC-VF
      for pancreatic cancer.

PMID- 16451099
TI  - Indapamide sustained release: a review of its use in the treatment of
      hypertension.
AB  - A low-dose sustained-release (SR) formulation of the thiazide-type diuretic
      indapamide, indapamide SR (Natrilix SR), retains the antihypertensive activity of
      the immediate-release (IR) formulation, with a smoother pharmacokinetic profile.
      In well controlled 12- to 52-week clinical trials, indapamide SR 1.5 mg/day was
      well tolerated and reduced blood pressure as effectively as therapeutic dosages
      of amlodipine, candesartan, enalapril, hydrochlorothiazide or indapamide IR.
      Indapamide SR was also more effective than enalapril in reducing left ventricular
      hypertrophy (LVH), and similar reductions in renal end-organ damage, assessed by
      microalbuminuria, were seen with indapamide SR- and enalapril-based
      antihypertensive strategies. Indapamide SR provides an effective option for
      initial antihypertensive monotherapy and a basis for multidrug antihypertensive
      strategies.

PMID- 16451104
TI  - Meeting on planning Plasmodium vivax vaccine efficacy trials. July 20-21, 2004,
      Singapore.

PMID- 16451105
TI  - Modern approaches to therapeutic vaccination as treatment for type 1 respiratory
      hypersensitivity (allergy) treatment.
AB  - The incidence of respiratory and other allergies has increased dramatically in
      many countries over the last few decades. Drug treatment is symptomatic and has a
      minimal effect on the underlying immunological dysfunction. This disease process
      may, however, be modified by allergy vaccination, which is typically applied by
      injecting increasing strengths of the offending allergens. Its use has been
      fairly limited owing to long injection schedules involving many visits to the
      physician, occasional local or systemic side effects, perceived limited efficacy
      and poor compliance. A greater understanding of the immunological mechanisms
      involved in allergy vaccination has led recently to the development of new
      generations of products with properties that address some of these issues, and
      these advances are likely to increase the successful use of the therapy.

PMID- 16451106
TI  - Human leukocyte antigen polymorphisms: variable humoral immune responses to viral
      vaccines.
AB  - Antibody formation in response to antigen stimulation remains the basis for
      measuring an individual's response and protection for most viral vaccines. A
      significant proportion of the variation in individual humoral immune response to
      vaccination appears to be genetic. The collection of genes found on chromosome 6
      forming the human leukocyte antigen system provides one of the greatest sources
      of genetic variation in individuals with respect to their immunological
      responses. Recent research has demonstrated significant associations between
      vaccine response and human leukocyte antigen alleles. These associations not only
      explain why vaccine-induced humoral immune responses vary among individuals and
      between populations, but these variations may also hold the key to the
      development of future generations of vaccines.

PMID- 16451107
TI  - Extraintestinal isolates of Escherichia coli: identification and prospects for
      vaccine development.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) cause a wide variety of
      infections that are responsible for significant morbidity, mortality and costs to
      our healthcare system. Thereby, the development of an efficacious ExPEC vaccine
      will minimize disease and may be cost-effective in selected patient groups.
      Surface polysaccharides, such as capsule, have been traditional targets for
      vaccine development. Considering that significant antigenic heterogeneity exists
      among surface polysaccharides present in various ExPEC strains, their use as
      vaccine candidates will be challenging. Therefore, alternative vaccine
      candidates/approaches are being identified and evaluated and are discussed in
      this review. The authors envision that an efficacious ExPEC vaccine will consist
      of either a polyvalent subunit vaccine or a genetically engineered killed whole
      cell vaccine.

PMID- 16451108
TI  - Role of natural killer cell function in dendritic cell-based vaccines.
AB  - Recent studies have elucidated the functional links between natural killer (NK)
      cells and, demonstrating the reciprocal activation of these cell types through NK
      DC interactions. The subsets of cells and molecular pathways involved in such
      interactions have been defined, and the possible anatomical sites of these
      interactions have also been reported. Murine experiments have demonstrated that
      injection of mature DCs induces rapid recruitment of NK cells to lymph nodes and
      that these NK cells provide interferon-gamma for Type 1 priming. Thus, there is
      an increasing body of in vivo evidence indicating that NK-DC interactions during
      the early phase of innate immunity can impact the quality and magnitude of the
      subsequent adaptive immune response. Importantly, these studies imply that NK
      cells might not serve merely as cytotoxic lymphocytes combating viral pathogens
      and malignant tumors, but must also be considered as important immunoregulatory
      cells with a significant influence on adaptive immunity. In contrast to the large
      volume of knowledge obtained through basic research, there is a relative paucity
      of information regarding NK cell function in adaptive immunity from clinical
      trials, as few DC vaccine studies have attempted to evaluate the nonspecific, yet
      potentially clinically relevant, NK response to immunization. In this article,
      the authors will review studies focusing on NK-DC interactions and highlight the
      most recent clinical findings relating to the potential role of NK cells in DC
      based vaccine therapy.

PMID- 16451109
TI  - Progress towards an effective syphilis vaccine: the past, present and future.
AB  - Syphilis is a disease caused by infection with the spirochetal pathogen Treponema
      pallidum subspp. pallidum. Despite intensive efforts, the unusual biology of T.
      pallidum has hindered progress towards the development of a vaccine to prevent
      infection. This review describes previous endeavors to develop a syphilis
      vaccine, outlines the key issues in the field and proposes new directions in the
      design of a T. pallidum vaccine. Following a brief overview of the disease
      symptoms, epidemiology, diagnosis and treatment, a case is put forward for the
      benefit of pursuing a syphilis vaccine. Relevant material concerning immunity to
      T. pallidum infection is summarized and evaluated, and pilot experiments
      describing the use of whole-cell bacterin vaccines and similar preparations are
      included. A detailed section concerning subunit vaccines is provided,
      incorporating discussions pertaining to relevant antigen selection, the
      identification of putative T. pallidum surface-exposed outer membrane proteins,
      factors hindering previous attempts to vaccinate with recombinant outer membrane
      proteins, problems and pitfalls of syphilis outer membrane protein-based
      vaccines, anti-attachment vaccines and the potential use of nonprotein subunit
      preparations as vaccinogens. Subsequently, critical aspects concerning vaccine
      antigen preparation and delivery are noted, including protein conformation,
      synergy, post-translational modifications, live attenuated organisms as vaccine
      vectors, prime-boost methodologies, adjuvant selection and immunization routes.
      Finally, animal models are discussed with particular reference to
      immunoprotection studies. A more thorough understanding of immunity to syphilis,
      a comprehensive assessment of the immunoprotective capacity of the putative
      surface-accessible antigens of T. pallidum and utilization of the latest advances
      in vaccine science should set the scene for future development of a syphilis
      vaccine.

PMID- 16451110
TI  - Advances in vaccine development against the pre-erythrocytic stage of Plasmodium
      falciparum malaria.
AB  - With approximately 2.4 billion people at risk, Plasmodium falciparum malaria
      infection caused by an infectious bite of an Anopheles mosquito continues to be a
      major cause of mortality and morbidity, mainly in the tropics and subtropics.
      Measures to control the mosquito vector on a broad scale are expensive and need
      to be maintained continuously. The rapid emergence of parasite strains that are
      resistant to affordable drugs highlights the urgent need for a cheap and
      effective vaccine. Candidate vaccines that have been developed to date target
      different stages of the parasite life cycle. This review describes the recent
      advances in the development of a vaccine that aims to terminate the infection at
      its first stage in the liver. The candidate vaccines that are currently under
      clinical evaluation are introduced and the results from recent trials discussed.
      The review aims to explain the immunologic challenges a successful vaccine has to
      meet, as well as the different strategies that are currently employed in an
      attempt to induce a protective immune response. Furthermore, an outline of
      available options to be tested in the near future will be presented.

PMID- 16451111
TI  - Genomic and proteomic approaches to vaccine candidate identification for
      Anaplasma marginale.
AB  - Outer membrane protein preparations have been demonstrated to elicit protective
      immunity for Anaplasma marginale. Attempts to recreate this protective immunity
      using known surface proteins have been unsuccessful; therefore, novel outer
      membrane proteins have been searched for using a proteomic/genomic approach.
      Annotation of the whole genome sequence identified 62 outer membrane protein
      candidates based on sequence similarity to known surface proteins. In a
      proteomics approach for the identification of immunostimulatory outer membrane
      proteins, outer membrane preparations that were separated on 2D gels were used to
      immunize calves . Antisera from the calves were used to detect immunoreactive
      proteins, which were then selected and subjected to mass spectrometric analyses.
      These data were mapped back to the annotated A. marginale genome and have
      identified several new outer membrane proteins that are vaccine candidates.

PMID- 16451112
TI  - Molecular approaches for new vaccines against allergy.
AB  - Type I allergy represents an important health problem that is currently affecting
      approximately 25% of the population in Western countries. Immunotherapy, the only
      causative treatment of Type I allergy, is currently performed with crude allergen
      extracts, which contain unpredictable amounts of allergenic, as well as
      nonallergenic, components. The application of molecular biology for allergen
      characterization has revealed the molecular nature of the most common allergens
      and allowed the production of recombinant allergens that equal natural allergens.
      Based on this knowledge, several different strategies to improve immunotherapy
      have become available. Until now, T-cell peptides, selected wild-type-like
      recombinant allergens and genetically modified hypoallergenic allergen
      derivatives have been evaluated in clinical trials in patients. Immunotherapy
      based on T-cell peptides has focused on allergen-specific T-cell responses,
      whereas genetically modified recombinant allergen molecules offer the advantage
      of combining T-cell and B-cell epitopes. Genetically modified recombinant birch
      pollen derivatives (Bet v 1-fragments, Bet v 1-trimer) have been evaluated in a
      double-blind, placebo-controlled, multicenter study. Vaccination with the Bet v 1
      derivatives improved symptoms of birch pollen allergy, induced a healthy allergen
      specific immunoglobulin G response and led to a significant reduction of
      seasonally induced boosts of immunoglobulin E.

PMID- 16451113
TI  - Influenza vaccine in patients with asthma.
AB  - Influenza virus continues to be a major cause of respiratory infection and is an
      important contributor to morbidity and mortality in at-risk populations,
      including those with underlying pulmonary conditions such as asthma. Vaccination
      with inactivated influenza vaccine remains the most popular method in controlling
      influenza through prevention. Current guidelines recommend the administration of
      the influenza vaccine to all patients with asthma. However, a third or fewer of
      those patients with asthma are currently receiving this vaccine. In this review,
      the risk-versus-benefit of influenza vaccination in children and adults with
      asthma is evaluated, based on the current evidence.

PMID- 16451114
TI  - Equine herpesvirus type 1 modified live virus vaccines: quo vaditis?
AB  - Infections of horses with equine herpesvirus type 1 (EHV-1) have garnered new
      attention over the last few years. Devastating outbreaks occurring worldwide,
      primarily of the neurologic form of the disease, have resulted in a reassessment
      of the control strategies, and particularly the prophylactic measures, that are
      necessary to keep the infection and spread of disease in check. Most of the
      available EHV-1 vaccines are based on preparations of inactivated virus, which
      are applied monovalently for prevention of EHV-1-caused abortion in pregnant
      mares or as part of multivalent vaccines to prevent respiratory disease. Despite
      the importance of an induction of cytotoxic immune responses for protection
      against EHV-1-induced disease, only two modified live virus vaccine preparations,
      which are both based on the avirulent EHV-1 strain RacH and were developed more
      than 40 years ago, are commercially available. Current efforts focus on
      exploiting the available infectious bacterial artificial chromosome clones of
      various EHV-1 strains to engineer a new generation of modified live virus
      vaccines. Both more efficient and long-lasting anti-EHV-1 immunity and delivery
      of immunogens of other pathogens are attempted and within immediate reach. The
      improvement of modified live virus vaccines will likely be a major focus of
      research in the future, and will hopefully help to more completely protect horses
      against one of the most important and devastating viral diseases.

PMID- 16451115
TI  - Sheep-associated malignant catarrhal fever virus: prospects for vaccine
      development.
AB  - Sheep-associated malignant catarrhal fever is emerging as a significant problem
      for several ruminant species worldwide. The inability to propagate the causative
      agent, ovine herpesvirus 2, in vitro has seriously hindered research efforts in
      the development of effective programs for control of the disease in clinically
      susceptible hosts. Recent molecular technologic advances have provided powerful
      tools for investigating this difficult-to-study virus. Identification of the
      infectious virus source, establishment of experimental animal models and
      completion of sequencing the genome for ovine herpesvirus 2 have put us in a
      position to pursue the development of vaccines for control of the disease. In
      this review, the authors briefly describe the current understanding of ovine
      herpesvirus 2 and prospectively discuss vaccine development against the virus.

PMID- 16451116
TI  - Poultry coccidiosis: recent advancements in control measures and vaccine
      development.
AB  - Coccidiosis is recognized as the major parasitic disease of poultry and is caused
      by the apicomplexan protozoan Eimeria. Coccidiosis seriously impairs the growth
      and feed utilization of infected animals resulting in loss of productivity.
      Conventional disease control strategies rely heavily on chemoprophylaxis and, to
      a certain extent, live vaccines. Combined, these factors inflict tremendous
      economic losses to the world poultry industry in excess of USD 3 billion
      annually. Increasing regulations and bans on the use of anticoccidial drugs
      coupled with the associated costs in developing new drugs and live vaccines
      increases the need for the development of novel approaches and alternative
      control strategies for coccidiosis. This paper aims to review the current
      progress in understanding the host immune response to Eimeria and discuss current
      and potential strategies being developed for coccidiosis control in poultry.

PMID- 16451122
TI  - Relations between structure and function of the mitochondrial ADP/ATP carrier.
AB  - Import and export of metabolites through mitochondrial membranes are vital
      processes that are highly controlled and regulated at the level of the inner
      membrane. Proteins of the mitochondrial carrier family ( MCF ) are embedded in
      this membrane, and each member of the family achieves the selective transport of
      a specific metabolite. Among these, the ADP/ATP carrier transports ADP into the
      mitochondrial matrix and exports ATP toward the cytosol after its synthesis.
      Because of its natural abundance, the ADP/ATP carrier is the best characterized
      within MCF, and a high-resolution structure of one conformation is known. The
      overall structure is basket shaped and formed by six transmembrane helices that
      are not only tilted with respect to the membrane, but three of them are also
      kinked at the level of prolines. The functional mechanisms, nucleotide
      recognition, and conformational changes for the transport, suggested from the
      structure, are discussed along with the large body of biochemical and functional
      results.

PMID- 16451123
TI  - Alveolar recruitment during prone position: time matters.
AB  - Alveolar recruitment is one of the beneficial effects of prone positioning in
      patients with ARDS (acute respiratory distress syndrome). However, responses vary
      among patients and, therefore, we hypothesized that alveolar recruitment is an
      individual time-dependent process and its measurement might be helpful to 'dose'
      prone positioning individually. In 13 patients diagnosed with ARDS, EELV (end
      expiratory lung volume) was measured in the supine position, immediately after
      turning to the prone position, at 1, 2, 4 and 8 h in the prone position and after
      returning to the supine position. Responders were defined based on a 30% increase
      in oxygenation. EELV increased in responders, whereas it remained constant in non
      responders. The time course was different in individual patients. In some
      responders, a plateau was reached as early as 2-4 h, whereas, in others, 8 h of
      prone positioning was not sufficient to allow complete recruitment. The increase
      in lung volume was associated with both an increase in arterial oxygenation and a
      decrease in venous admixture. Furthermore, responders had significantly lower
      baseline EELVs than non-responders. In conclusion, alveolar recruitment during
      prone positioning has been characterized as an individual time-dependent process.
      Its measurement might be useful to apply prone positioning more individually and
      might also help to identify responders.

PMID- 16451124
TI  - The endogenous anti-angiogenic family of splice variants of VEGF, VEGFxxxb, are
      down-regulated in pre-eclamptic placentae at term.
AB  - PET (pre-eclamptic toxaemia) has recently been linked with alterations in
      production of a VEGFR1 [VEGF (vascular endothelial growth factor) receptor 1]
      splice variant that acts as a circulating inhibitor. We have recently described a
      family of naturally occurring splice variants of VEGF, termed VEGFxxxb, that also
      appear to act as inhibitors of conventional VEGFxxx-mediated angiogenesis. To
      determine whether alteration in splicing of VEGF-VEGFR family members extended
      beyond VEGFR1, we investigated the effect of pre-eclampsia on placental VEGFxxxb
      mRNA and protein expression. VEGFxxx and VEGFxxxb mRNA and protein were both
      found in normal human term placentae. VEGFxxx protein formed the majority of the
      total VEGF protein (980+/-195 pg/mg), whereas VEGFxxxb (11.5 pg/mg) was found to
      form a small part of the total VEGF protein expression (1.5+/-0.24%). Evidence
      for VEGF165b, VEGF121b and VEGF145b expression was found. In pre-eclamptic
      placentae, there was a significant down-regulation of VEGFxxxb isoforms, but a
      small up-regulation of VEGFxxx isoforms. In normal placenta VEGFxxxb and VEGFxxx
      concentrations were positively correlated (r=0.69, P<0.02), whereas in pre
      eclamptic placentae, there was a significant negative correlation between
      VEGFxxxb and VEGFxxx protein expression (r=-0.8, P<0.02), indicating that there
      was a significant uncoupling of the splicing regulation of the VEGF isoforms.
      Combined with previous studies showing increased soluble VEGFR1 isoforms in human
      pre-eclampsia, these data suggest that there may be a common mechanism in pre
      eclampsia that involves dysregulation of mRNA splicing of members of the VEGF
      VEGFR axis.

PMID- 16451125
TI  - Synergy of fatty acid and reactive alkenal activation of proton conductance
      through uncoupling protein 1 in mitochondria.
AB  - The kinetics of proton transport through mammalian UCP1 (uncoupling protein 1)
      expressed in yeast mitochondria were measured. There was little or no UCP1
      activity in the absence of added palmitate, but significant activity in its
      presence. The activator 4-HNE (4-hydroxy-2-nonenal) had little effect when added
      alone, but significantly enhanced proton conductance in the presence of added
      palmitate. Activation of the proton conductance of UCP1 was synergistic: proton
      conductance in the presence of both palmitate and 4-HNE was significantly greater
      than the sum of the individual effects. Mitochondria from control yeast
      transformed with empty vector showed no such synergy, showing that synergy is a
      property of UCP1. Activation by the 4-HNE analogue trans-cinnamate showed
      essentially the same characteristics as activation by 4-HNE. Mitochondria from
      brown adipose tissue also showed synergistic activation of GDP-sensitive proton
      conductance by palmitate and 4-HNE. These results show that reactive alkenals
      activate the proton conductance of UCP1 more strongly when fatty acids are also
      added, with implications for both mechanistic and physiological models of UCP1
      activation.

PMID- 16451126
TI  - Altered gene silencing and human diseases.
AB  - Epigenetic regulation of gene expression is mediated through several mechanisms,
      including modifications in DNA methylation, covalent modifications of core
      nucleosomal histones, rearrangement of histones and RNA interference. It is now
      clear that deregulation of epigenetic mechanisms cooperates with genetic
      alterations in the development and progression of several Mendelian disorders.
      Here, we summarize the recent findings that highlight how certain inherited
      diseases, such as Rett syndrome, Immunodeficiency-centromeric instability-facial
      anomalies syndrome, and facioscapulohumeral muscular dystrophy, result from
      altered gene silencing.

PMID- 16451127
TI  - Predictive genetic testing in young people for adult-onset conditions: where is
      the empirical evidence?
AB  - Predictive genetic testing in young people for severe, adult-onset conditions is
      advised against in current guidelines. Despite this, there has been considerable
      debate regarding the issue. Some perceive such testing as too potentially harmful
      to allow. Others perceive it as an opportunity for the promotion of benefit, an
      opportunity even for the prevention of harm. The only way to resolve this
      theoretical debate is to collect empirical data related to the effects of such
      testing when it occurs. However, more than 15 years after the debate began, there
      is virtually no such empirical evidence available. The reasons for this lack of
      evidence appear to relate to the rarity of such testing, which when it occurs is
      not studied systematically. Additionally, clinicians performing such tests may
      feel vulnerable in sharing the outcomes, given that such testing is contrary to
      current recommendations. We propose a way forward that entails the provision of
      tests to mature minors, where clinicians deem this appropriate. These tests
      should be performed as part of an international research collaboration,
      facilitated by one leading group.

PMID- 16451129
TI  - Loud and clear evidence for gene silencing by epigenetic mechanisms in autism
      spectrum and related neurodevelopmental disorders.

PMID- 16451133
TI  - CD36 expression and its relationship with obesity in blood cells from people with
      and without Prader-Willi syndrome.
AB  - Although Prader-Willi syndrome (PWS) has been linked to the loss of function of
      imprinted genes in 15q11q13, very little is known about the pathogenesis. Using
      quantitative real-time PCR, we have confirmed the previous observation of an
      abnormality of CD36 expression in cells with maternal uniparental disomy 15,
      obtained from a proband with mosaicism for PWS, by demonstrating reduced
      expression levels in blood cells from a series of non-mosaic probands with PWS.
      Furthermore, we have extended these observations to show that CD36 expression in
      a non-PWS population is inversely correlated with body mass index but that this
      correlation does not hold in PWS. CD36 which maps to 7q11.2 is the first gene
      outside the 15q11q13 region whose level of expression appears to be reduced in
      people with PWS. Low CD36 expression levels in PWS point to an abnormal control
      of lipid and glucose homeostasis which may explain the insatiable hunger in these
      patients.

PMID- 16451134
TI  - Functional variants of the lipoprotein lipase gene and the risk of preeclampsia
      among non-Hispanic Caucasian women.
AB  - Hypertriglyceridemia is an important pathophysiologic feature of preeclampsia, a
      common vascular disorder of pregnancy. Three well-documented functional variants
      (N291S, S447X, and D9N) of the lipoprotein lipase gene were related to
      hypertriglyceridemia. Results from the only two studies concerning the
      relationship between these variants and preeclampsia risk have been inconsistent.
      We investigated this relationship in a case-control study including 144
      preeclamptic and 290 normotensive pregnant women (all non-Hispanic Caucasians).
      We estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for
      maternal age, pre-pregnancy body mass index, and parity. After adjusting for
      covariates, women with the 291 N/S or S/S genotype had significantly increased
      risk of preeclampsia (OR 6.9, 95% CI 1.9-25.4) compared with women with the
      common 291N/N genotype. The 447 S/X or X/X genotype was not significantly
      associated with preeclampsia risk. The frequency of the 9N variant allele was
      1.8% in controls, while this allele was not observed among cases. Haplotype
      9D/291S/447S was strongly associated with higher risk of preeclampsia as compared
      with the most common haplotype 9D/291N/447S (adjusted OR 6.6, 95% CI 1.7-25.0).
      Results from our study support the thesis that abnormal lipid metabolism is
      important in the pathogenesis of preeclampsia.

PMID- 16451135
TI  - Germline MSH2 and MLH1 mutational spectrum including large rearrangements in
      HNPCC families from Poland (update study).
AB  - Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 account for a
      significant proportion of hereditary non-polyposis colorectal cancer (HNPCC)
      families. One approach by which development of an efficient DNA-testing procedure
      can be implemented is to describe the nature and frequency of common mutations in
      particular ethnic groups. Two hundred and twenty-six patients from families
      matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were
      screened for MSH2 and MLH1 germline mutations. Fifty different pathogenic
      mutations were found, 25 in MSH2 and 25 in MLH1. Twenty-four of these had not
      previously been described in other populations. Among our 78 families with MSH2
      or MLH1 mutations, 54 (69.2%) were affected by recurrent mutations including 38
      found at least twice in our own series. Two of the most frequent alterations were
      a substitution of A to T at the splice donor site of intron 5 of MSH2 and a
      missense change (A681T) of MLH1 found in 10 and eight families, respectively.
      Among large deletions detected by the multiplex ligation-dependent probe
      amplification assay, exon 9 deletions in the MSH2 gene were found in two
      families. Our results indicate that a screening protocol specific for the Polish
      population that is limited to the detection of all reported mutations will result
      in the identification of the majority of changes present in MLH1 and MSH2 genes
      in Polish HNPCC kindreds.

PMID- 16451136
TI  - Initial screening transferrin saturation values, serum ferritin concentrations,
      and HFE genotypes in Native Americans and whites in the Hemochromatosis and Iron
      Overload Screening Study.
AB  - We compared initial screening transferrin saturation (TfSat) and serum ferritin
      (SF) phenotypes and HFE C282Y and H63D genotypes of 645 Native American and
      43,453 white Hemochromatosis and Iron Overload Screening Study participants who
      did not report a previous diagnosis of hemochromatosis or iron overload. Elevated
      measurements were defined as TfSat >50% in men and >45% in women and SF >300
      ng/ml in men and >200 ng/ml in women. Mean TfSat was 31% in Native American men
      and 32% in white men (p = 0.0337) and 25% in Native American women and 27% in
      white women (p < 0.0001). Mean SF was 153 microg/l in Native American and 151
      microg/l in white men (p = 0.8256); mean SF was 55 microg/l in Native American
      women and 63 microg/l in white women (p = 0.0015). The C282Y allele frequency was
      0.0340 in Native Americans and 0.0683 in whites (p < 0.0001). The H63D allele
      frequency was 0.1150 in Native Americans and 0.1532 in whites (p = 0.0001). We
      conclude that the screening TfSat and SF phenotypes of Native Americans are
      similar to those of whites. The allele frequencies of HFE C282Y and H63D are
      significantly lower in Native Americans than in whites.

PMID- 16451138
TI  - Detection of human chromosomal abnormalities using a new technique combining 4',6
      diamidino-2-phenyl-indole staining and image analysis.
AB  - Chromosomal abnormalities are associated with a variety of diseases. We have
      developed a new technique for detecting chromosomal abnormalities, and the
      technique combines conventional 4',6-diamidino-2-phenyl-indole staining (DAPI)
      with image analysis. The image analysis consists of two simple steps:
      deconvolution and three-dimensional reconstruction. The technique has been
      reported for analyzing plant chromosomes but has not been applied to analyze
      human chromosomes yet. To test the technique, we analyzed five translocations:
      46,XX,t(3;21)(12;18), 46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and
      46,XY,t(3;7). The results showed that the karyotype of the 46,XX,t(3;21)(12;18)
      was 46,XX,t(3;21)(q11.1;p13),t(12;18) (q21.2;q23), and the karyotypes of the
      46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and 46,XY,t(3;7) were
      46,XX,t(11;22)(q23;q12.1); 46,XY,t(7;22)(q32;q13.2); 46,XY,t(11;18)(q13.3;q23),
      and 46,XY,t(3;7)(q22.1;p13), respectively. The identity of derivative chromosomes
      involved in the translocations was verified by chromosome painting as well as
      FISH analyses with centromere probes. The new technique has two advantages: the
      procedure is simple and convenient, and the results are accurate. The technique
      has the potential to be used in cytogenetic studies and clinical diagnosis of
      human diseases in the future.

PMID- 16451137
TI  - Multiplex ligation-dependent probe amplification to detect subtelomeric
      rearrangements in routine diagnostics.
AB  - Subtelomeric rearrangements are believed to be responsible for 5-7% of idiopathic
      mental retardation cases. Due to the relative complexity and high cost of the
      screening methods used till now, only preselected patient populations including
      mostly the more severely affected cases have been screened. Recently, multiplex
      ligation-dependent probe amplification (MLPA) has been adapted for use in
      subtelomeric screening, and we have incorporated this technique into routine
      diagnostics of our laboratory. Since the evaluation of MLPA as a screening
      method, we tested 275 unselected patients with idiopathic mental retardation and
      detected 12 possible subtelomeric aberrations: a der(11)t(11;20)(qter;qter), a
      19pter duplication, a der(18)t(18;10)(qter; pter), a 15qter deletion, a 8pter
      deletion, a 6qter deletion, a der(X)t(X;1)(pter;qter), a der(X)t(X;3)(pter;pter),
      a 5qter duplication, a 3pter deletion, and two 3qter duplications. The patients
      can be subdivided into two groups: the first containing de novo rearrangements
      that are likely related to the clinical presentation of the patient and the
      second including aberrations also present in one of the parents that may or may
      not be causative of the mental retardation. In our patient cohort, five (1.8%)
      subtelomeric rearrangements were de novo, three (1.1%) rearrangements were
      familial and suggestively disease causing, and four (1.5%) were possible
      polymorphisms. This high frequency of subtelomeric abnormalities detected in an
      unselected population warrants further investigation about the feasibility of
      routine screening for subtelomeric aberrations in mentally retarded patients.

PMID- 16451139
TI  - Genetic and biochemical approach to early prenatal diagnosis in a family with mut
      methylmalonic aciduria.
AB  - Genetic and biochemical prenatal diagnosis was performed at 11 weeks of gestation
      in a family with a proband affected by mut methylmalonic aciduria (MMA) and
      homozygotes for the MUT gene c.643G>A (p.Gly215Ser) mutation. Both chorionic
      villus and amniotic fluid samples were used. The presence of high levels of
      methylmalonic acid and propionylcarnitine determined by gas chromatography/mass
      spectrometry and LC/MS/MS analysis, respectively, and the identification of the
      p.Gly215Ser at a homozygous level in foetal DNA allowed a certain, rapid and
      early diagnosis. To our knowledge, this is the first mut MMA prenatal diagnosis
      carried out by genetic and biochemical approach.

PMID- 16451140
TI  - Maternal urinary steroid profiles in prenatal diagnosis of Smith-Lemli-Opitz
      syndrome: first patient series comparing biochemical and molecular studies.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by
      reduced activity of 7-dehydrocholesterol (7DHC) reductase, resulting in a
      decreased level of cholesterol and increased concentrations of 7DHC and 8DHC in
      body fluids and tissues. Ten pregnancies at 25% risk of SLOS underwent prenatal
      testing. Diagnostic studies included DHCR7 mutation analysis in chorionic villus
      samples, amniotic fluid sterol analysis and serial measurements of oestriol (E3),
      pregnanetriol (PT), 7-dehydropregnanetriol (7DHPT) and 8-dehydroesteriol (8DHE3)
      concentrations in maternal urine samples obtained between 9 and 20 weeks of
      gestation. All tests were diagnostic and revealed nine unaffected foetuses (two
      normal homozygotes and seven DHCR7 heterozygotes) and one affected foetus. In the
      affected pregnancy, 7DHC and 8DHC in amniotic fluid were 9.87 and 3.7 microg/ml,
      respectively [reference range (RR) 0.0026 +/- 0.0015 microg/ml and not
      detectable, respectively] and maternal urinary steroid analyses showed increased
      ratios of 7DHPT/PT and 8DHE3/E3 of 0.74 and 1.7, respectively (RR 0-0.0147 and 0
      0.019). In the heterozygous foetuses, 7DHPT/PT and 8DHE3/E3 ratios did not exceed
      those found in 48 normal controls. This is the first series of prenatal
      diagnostic testing for SLOS where non-invasive biochemical testing was performed
      in tandem with invasive diagnostic testing. We conclude that steroid measurements
      in maternal urine are a reliable means of prenatal diagnosis for SLOS.

PMID- 16451142
TI  - Genetic counseling for mental illness: goals resemble counseling goals for other
      common conditions.

PMID- 16451141
TI  - Adams-Oliver syndrome: clinical description of a four-generation family and
      exclusion of five candidate genes.
AB  - We present a Belgian Adams-Oliver syndrome (AOS) family with 10 affected
      individuals over four generations, of which six were available for this study.
      Clinical symptoms observed in these patients were very variable as previously
      reported in other families and included large areas of alopecia on the vertex of
      the skull and serious limb reduction defects with agenesis of all toes of one
      foot. To identify the disease-causing gene, we sequenced the MSX1, CART1, P63
      (P73L), RUNX2, and HOXD13 genes in this family and nine previously reported
      families, but no disease-causing mutations were found. Further investigation is
      ongoing in these families in order to identify the genetic cause of AOS.

PMID- 16451144
TI  - A qualitative systematic review of peri-operative dextromethorphan in post
      operative pain.
AB  - BACKGROUND: The N-methyl-D-aspartate (NMDA) receptor antagonist, dextromethorphan
      (DM), has received interest as an adjunctive agent in post-operative pain
      management. Clinical trials have been contradictory. This systematic review aims
      to evaluate the available literature examining the analgesic efficacy of DM in
      post-operative patients. METHODS: Twenty-eight randomized, double-blind, clinical
      studies, with 40 comparisons, including a variety of dosing regimens comparing DM
      treatment with placebo, were included. Meta-analysis was intended but deemed to
      be inappropriate because of the substantial difference in methodology and
      reporting between trials. The outcome measures (pain scores at rest, time to
      first analgesic request and supplemental analgesic consumption) were evaluated
      qualitatively by significant difference (P<0.05) as reported in the original
      investigations. RESULTS: DM did not reduce the post-operative pain score with a
      clinically significant magnitude. The time to first analgesic request was
      significantly prolonged in most comparisons with DM. Significant decreases in
      supplemental opioid consumption were observed in the majority of parenteral DM
      studies and in about one-half of the oral studies. The decreases were of
      questionable clinical importance in most comparisons, although a relationship
      between a decrease in opioid consumption and opioid-related side-effects was
      established in some studies. CONCLUSION: Based on the studies available, DM has
      the potential to be a safe adjunctive agent to opioid analgesia in post-operative
      pain management, but the consistency of the potential opioid-sparing and pain
      reducing effect must be questioned. Consequently, it is not possible to recommend
      dose regimens or routine clinical use of DM in post-operative pain. The route of
      administration may be important for the beneficial effect.

PMID- 16451145
TI  - Early recovery, cognitive function and costs of a desflurane inhalational vs. a
      total intravenous anaesthesia regimen in long-term surgery.
AB  - BACKGROUND: The purpose of the study was to compare time of recovery, return of
      cognitive function, post-anaesthetic care unit (PACU) stay and costs of a
      propofol/remifentanil (TIVA) with a desflurane/fentanyl-based anaesthesia
      (desflurane group) in surgical procedures lasting more than 150 min. METHODS:
      Forty-nine patients undergoing elective abdominal prostatectomy were allocated
      randomly to receive bispectal index (BIS)-controlled desflurane/fentanyl (n=24)
      or propofol/remifentanil (n=25). Awakening, clinical recovery, direct drug
      acquisition and post-operative pain treatment were documented. Cognitive skills
      were tested using the Mini-Mental Status (MMST) test. RESULTS: Extubation was
      significantly faster with desflurane (6.9+/-3.5 min) than with TIVA (11.2+/-4.0
      min) as well as times for stating name and date of birth (desflurane: 6.1+/-3.9
      and 6.6+/-4.0 min; TIVA: 12.4+/-11.5 min and 13.4+/-11.3 min). There were no
      significant differences in PACU discharge times or MMS scores between the groups.
      Significantly more patients suffered post-operative nausea and vomiting (PONV) in
      the desflurane (33% vs. 0%) than the TIVA group. Overall costs were significantly
      higher in the TIVA (58.8+/-11.6 euro) than in the desflurane group (35.0+/-5.7
      euro). CONCLUSION: Patients undergoing prolonged surgical procedures showed a
      faster early recovery after desflurane/fentanyl than using TIVA, whereas stay in
      the PACU and recovery of cognitive function were similar in both groups. Costs of
      a TIVA regimen were significantly higher than using a desflurane-based
      anaesthesia technique.

PMID- 16451146
TI  - Postoperative outcome among elderly patients after general anesthesia.
AB  - BACKGROUND: Preoperative decision-making for elderly patients requires a long
      term perspective. The aim of this study was to identify preoperative risk factors
      for decreased 1- to 5-year survival rates and to compare the survival rates of
      stratified risk groups with those of the sex- and age-matched general population.
      METHODS: Subjects were 406 patients, aged 80 years or older, who underwent
      surgery with general anesthesia. Higher age, male sex, dependency in daily
      living, low serum albumin level, malignancy, abdominal surgery, emergency surgery
      and high ASA class were analyzed for survival using univariate and multivariate
      analysis with Cox's proportional hazard model. One- to 5-year survival rates were
      estimated using life table analysis for patients divided by risk factors. The
      survival data were also compared with the cumulative survival rates of the sex-
      and age-matched general population. RESULTS: Multivariate analysis identified
      three factors that were significantly associated with decreased survival rates:
      male sex, dependency in daily living and abdominal surgery. Long-term survival
      among patients older than 90 years was comparable to those of the general
      population. Although improved in recent years, overall survival rates were much
      lower than expected due to poor outcome among patients dependent in daily living
      and those who underwent abdominal surgery. CONCLUSIONS: In patients 80 years or
      older who underwent surgery with general anesthesia, independent risk factors for
      decreased survival are male sex, dependency in daily living and abdominal
      surgery. Only patients independent in daily living who underwent non-abdominal
      surgery had survival rates comparable to those of the general population.

PMID- 16451147
TI  - Supplemental 80% oxygen does not attenuate post-operative nausea and vomiting
      after breast surgery.
AB  - BACKGROUND: Although supplemental oxygen has been shown to be as effective as
      ondansetron in the prevention of post-operative nausea and vomiting (PONV) in one
      study in abdominal surgery patients, the antiemetic efficacy of supplemental
      oxygen is controversial on the basis of studies with other patients. We compared
      the efficacy of 80% and 30% oxygen in decreasing PONV in breast surgery.
      Ondansetron was used as an active control. METHODS: Ninety patients were given a
      standardized sevoflurane anesthetic. They were randomly assigned to three groups:
      30% oxygen in nitrogen and saline 2 ml intravenously (i.v.) at the end of surgery
      (group 30); 80% oxygen in nitrogen and saline 2 ml (group 80); and 30% oxygen in
      nitrogen and ondansetron 4 mg (group O). Oxygen was administered during surgery
      and up to 2 h after surgery. RESULTS: The incidence of total response (no
      retching or vomiting, no nausea) during the first 24 post-operative hours was not
      different between group 80 (17%) and group 30 (11%) but was higher in group O
      (43%) than in group 30 (P<0.05). Compared with group O, patients in group 80
      experienced more vomiting during the study period 0-24 h (66% vs. 32%; P<0.05)
      and more nausea during the period 6-24 h (72% vs. 39%; P<0.05). There was no
      difference between the groups in their risk for PONV, pain scores, opioid
      consumption, or patient satisfaction. CONCLUSIONS: In this study, supplemental
      80% oxygen administration failed to decrease PONV in breast surgery.

PMID- 16451148
TI  - Response Entropy is not more sensitive than State Entropy in distinguishing the
      use of esmolol instead of remifentanil in patients undergoing gynaecological
      laparoscopy.
AB  - BACKGROUND: Monitoring of analgesia remains a challenge during general
      anaesthesia. Activation of Response Entropy (RE) to painful stimuli has been
      suggested to be a sign of inadequate analgesia. We evaluated the ability of RE to
      be more sensitive than State Entropy (SE) in measuring nociception in patients
      undergoing gynaecological laparoscopy. Our hypothesis was that while keeping SE
      at a predetermined level, RE would be higher in patients receiving a beta
      blocking agent (esmolol) instead of an opioid (remifentanil) during a
      propofol/nitrous oxide anaesthesia. METHODS: Fifty-one women aged between 22-53
      years were randomly assigned to receive esmolol (n=25) or remifentanil (n=26). SE
      was kept at 50+/-5. RE and SE were recorded at an interval of 30 s to 2 min and
      the areas under the RE and SE value-time curves (AUCRE and AUCSE) were calculated
      during the time of intubation and start of surgery as well as during the entire
      anaesthesia. The difference between RE and SE recordings in both groups was
      determined by subtracting the AUCSE from the corresponding AUCRE. Movements of
      the patients were recorded. RESULTS: No significant differences were detected in
      any of the several AUC values between the groups. The difference between RE and
      SE recordings was similar in both groups. Every patient in the esmolol group
      moved some time during the procedure interfering with surgery while no one in the
      remifentanil group moved. CONCLUSION: In patients undergoing gynaecological
      laparoscopic day-case surgery, RE seems not to be more sensitive than SE in
      guiding the use of opioids during general anaesthesia.

PMID- 16451149
TI  - Comparison of airway management with the intubating laryngeal mask, laryngeal
      tube and CobraPLA by paramedical students in anaesthetized patients.
AB  - BACKGROUND: Because of the importance of airway management in emergency care,
      alternative methods with shorter learning curves for inexperienced personnel have
      been looked for as a substitute for endotracheal intubation (ETI). METHODS: We
      compared the success of insertion, oxygenation and ventilation of the intubating
      laryngeal mask (ILMA), laryngeal tube (LT) and CobraPLA (COB) in anaesthetized
      patients when used by paramedical students. After informed consent, 96 patients
      were monitored and anaesthetized for general surgery without the use of a muscle
      relaxant. After the induction of anaesthesia, 32 paramedical students inserted
      the ILMA, LT or COB in a random order and ventilated the patient for a 60-s
      period. The number of insertion attempts, the time needed for insertion, and
      oxygenation and ventilation parameters were recorded. The students gave a
      subjective evaluation of the airway devices after the test. RESULTS: Twenty-four
      of the 32 students (75%) successfully inserted ILMA at the first attempt,
      compared with 14 of 32 (44%) for LT and seven of 32 (22%) for COB (P<0.001, ILMA
      vs. COB). One student failed to insert ILMA after all three attempts, compared
      with seven of 32 (21%) using LT and seven of 32 (21%) using COB (P=not
      significant). Oxygenation and ventilation parameters did not differ between the
      groups after successful insertion. CONCLUSION: Clinically inexperienced
      paramedical students can successfully use ILMA in anaesthetized patients. Further
      investigations are warranted to study whether ILMA or LT can replace ETI in
      emergency airway management when used by inexperienced medical or paramedical
      staff.

PMID- 16451150
TI  - An interchangeable Mapleson A-E breathing system is practical and cost effective.
AB  - BACKGROUND: In locations where oxygen and anesthesia gas supplies are limited,
      and where circle systems are not practical, means to reduce fresh gas flow during
      maintenance of inhalational anesthesia are of potential value. We investigated
      whether a common transport breathing apparatus could be modified to allow
      interchange between Mapleson D (Map-D) and Mapleson A (Map A) configurations.
      METHODS: A common Map-D transport system was converted to a Map-A system by
      switching positions of the exhaust valve and the elbow connector where fresh gas
      is delivered; these two breathing systems were compared in this study. The key
      question was whether rebreathing of CO2 could be eliminated at a lower fresh gas
      flow rate (FGF) with the Map-A design. A structured protocol was followed.
      RESULTS: A mean decrease in FGF of 2.8 l/min was seen with the Map-A apparatus
      when compared with the Map-D (P=0.003). With no significant differences in
      physiologic or anesthetic variables, FGF/V(E) was significantly lower with the
      Mapleson A configuration than with the Mapleson D system design (1.1 vs. 1.8;
      P=0.007). The extent to which FGF could be lowered when switching between
      Mapleson D and A systems correlated strongly with the patients' respiratory rate
      while under anesthesia (r=0.45, P<0.01). CONCLUSIONS: Cost and resource savings
      can be realized through the use of a breathing system modification that achieves
      appropriate ventilation at lower fresh gas flows.

PMID- 16451151
TI  - The sensitivity and specificity of three common statistical rules for the
      classification of post-operative cognitive dysfunction following coronary artery
      bypass graft surgery.
AB  - BACKGROUND: The application of statistical rules to determine post-operative
      cognitive dysfunction (POCD) has varied, and partially explains the wide range of
      reported incidences of POCD in the literature. The current study assessed the
      sensitivity and specificity of three commonly used statistical rules in a sample
      of coronary artery bypass graft (CABG) patients and healthy non-surgical
      controls. METHODS: Two hundred and four CABG patients [mean age, 68.8 years;
      standard deviation (SD), 7.0 years] completed neuropsychological assessment pre
      operatively (baseline) and 1 week and 3 months post-operatively. Ninety age- and
      gender-matched non-surgical controls (mean age, 67.8 years; SD, 7.9 years)
      completed the same tasks at the same time points. POCD was determined in each
      group using three rules: the 1SD decline on two or more tasks; the 20% decline on
      20% of tasks rule; and a modified reliable change index. RESULTS: The modified
      reliable change index demonstrated the greatest combination of sensitivity and
      specificity. The 20% decline on 20% of tasks rule detected the largest incidence
      of impairment in the CABG group, but showed large incidences of false positive
      classifications in the control group. The 1SD rule detected the lowest incidence
      of POCD in the CABG group, but detected a larger incidence of impairment in the
      control group. CONCLUSIONS: The use of the modified reliable change index is
      recommended, given the sensitivity to change it displayed and the low rates of
      false positive classification in the control sample. The use of control groups in
      future research is also recommended.

PMID- 16451152
TI  - Significance of working conditions on burnout in anesthetists.
AB  - BACKGROUND: The influence of working conditions on the development of burnout
      syndrome was assessed in anesthetists working at a university hospital. METHODS:
      Self-reporting questionnaires were used to assess physical health and emotional
      well-being (Health and Stress Profile), burnout syndrome (Maslach Burnout
      Inventory) and working conditions (Instrument for Stress-Oriented Task Analysis)
      in anesthetists. RESULTS: Twenty-three anesthetists (25.8%) appeared to be at
      risk for burnout, and three anesthetists (3.4%) had already developed full-blown
      burnout syndrome. Anesthetists at risk for burnout more frequently suffered from
      limited complexity of work (P=0.001), lacking individual time control (P=0.004),
      lack of participation possibilities (P=0.012), and had more physical complaints
      (P=0.017) and greater job dissatisfaction (P=0.002) than did their colleagues
      with no burnout symptoms. CONCLUSION: Job conditions providing little opportunity
      to influence work pace and participation contribute to the development of burnout
      syndrome. Communication and contact with colleagues appear to be an important
      preventive regulative.

PMID- 16451153
TI  - Oxygenation within the first 120 h following coronary artery bypass grafting.
      Influence of systemic hypothermia (32 degrees C) or normothermia (36 degrees C)
      during the cardiopulmonary bypass: a randomized clinical trial.
AB  - BACKGROUND: Lung function is often impaired after cardiac surgery performed under
      cardiopulmonary bypass (CPB). Normothermic CPB has become more common, but it
      remains unknown whether it reduces post-operative lung function compared with
      hypothermic CPB. The aim of this study was to investigate oxygenation within the
      first 120 h after systemic hypothermia and normothermia under CPB. METHODS:
      Thirty patients undergoing coronary artery bypass grafting (CABG) were randomized
      to either hypothermic (32 degrees C) or normothermic (36 degrees C) CPB.
      Oxygenation was studied by a simple method for the estimation of intrapulmonary
      shunt and ventilation-perfusion (V/Q) mismatch pre-operatively and 4, 48 and 120
      h post-operatively by changing Fio2 in four to six steps. V/Q mismatch was
      described with DeltaPo2 (normal values, 0-2.38 kPa). RESULTS: Shunt and V/Q
      mismatch (DeltaPo2) increased post-operatively in both groups (P<0.01), with no
      differences between the groups, and with the nadir values 48 h after surgery,
      i.e. shunt of 15% (5.8-25%) and DeltaPo2 of 3.0 kPa (0.8-14 kPa) [values given as
      median (range)]. CONCLUSIONS: Impaired oxygenation is prevalent and prolonged
      following CABG, with equal intensity after hypothermic and normothermic CPB.

PMID- 16451154
TI  - International Programme for Resource Use in Critical Care (IPOC)--a methodology
      and initial results of cost and provision in four European countries.
AB  - BACKGROUND: A standardized top-down costing method is not currently available
      internationally. An internally validated method developed in the UK was modified
      for use in critical care in different countries. Costs could then be compared
      using the World Health Organization's Purchasing Power Parities (WHO PPPs).
      METHODS: This was an observational, retrospective, cross-sectional, multicentre
      study set in four European countries: France, UK, Germany and Hungary. A total of
      329 adult intensive care units (ICUs) participated in the study. RESULTS: The
      costs are reported in international dollars ($) derived from the WHO PPP
      programme. The results show significant differences in resource use and costs of
      ICUs over the four countries. On the basis of the sum of the means for the major
      components, the average cost per patient day in UK hospitals was $1512, in French
      hospitals $934, in German hospitals $726 and in Hungarian hospitals $280.
      CONCLUSIONS: The reasons for such differences are poorly understood but warrant
      further investigation. This information will allow us to better adjust our
      measures of international ICU costs.

PMID- 16451155
TI  - Changes in respiratory mechanics and gas exchange during the acute respiratory
      distress syndrome.
AB  - BACKGROUND: The time course of impairment of respiratory mechanics and gas
      exchange in the acute respiratory distress syndrome (ARDS) remains poorly
      defined. We assessed the changes in respiratory mechanics and gas exchange during
      ARDS. We hypothesized that due to the changes in respiratory mechanics over time,
      ventilatory strategies based on rigid volume or pressure limits might fail to
      prevent overdistension throughout the disease process. METHODS: Seventeen severe
      ARDS patients {PaO2/FiO2 10.1 (9.2-14.3) kPa; 76 (69-107) mmHg [median (25th-75th
      percentiles)] and bilateral infiltrates} were studied during the acute,
      intermediate, and late stages of ARDS (at 1-3, 4-6 and 7 days after diagnosis).
      Severity of lung injury, gas exchange, and hemodynamics were assessed. Pressure
      volume (PV) curves of the respiratory system were obtained, and upper and lower
      inflection points (UIP, LIP) and recruitment were estimated. RESULTS: (1) UIP
      decreased from early to established (intermediate and late) ARDS [30 (28-30)
      cmH2O, 27 (25-30) cmH2O and 25 (23-28) cmH2O (P=0.014)]; (2) oxygenation improved
      in survivors and in patients with non-pulmonary etiology in late ARDS, whereas
      all patients developed hypercapnia from early to established ARDS; and (3) dead
      space ventilation and pulmonary shunt were larger in patients with pulmonary
      etiology during late ARDS. CONCLUSION: We found a decrease in UIP from acute to
      established ARDS. If applied to our data, the inspiratory pressure limit
      advocated by the ARDSnet (30 cmH2O) would produce ventilation over the UIP, with
      a consequent increased risk of overdistension in 12%, 43% and 65% of our patients
      during the acute, intermediate and late phases of ARDS, respectively. Lung
      protective strategies based on fixed tidal volume or pressure limits may thus not
      fully avoid the risk of lung overdistension throughout ARDS.

PMID- 16451156
TI  - The effect of tracheostomy on outcome in intensive care unit patients.
AB  - BACKGROUND: Percutaneous dilatation tracheostomy (PDT) is increasingly being used
      in the intensive care unit (ICU), and has probably increased the number of
      procedures performed. The primary aim of this study was to document the short-
      and long-term outcome of patients with a tracheostomy performed during an ICU
      stay. METHODS: Patients in our ICU who underwent an unplanned tracheostomy
      between 1997 and 2003 were included in this analysis. The type of tracheostomy
      (PDT or surgical tracheostomy) and time of the procedure were registered
      prospectively in our ICU database. Survival was followed using the People's
      Registry of Norway and morbidity data from the individual hospital record. These
      patients were also compared with a group of ICU patients ventilated for more than
      24 h, but managed without a tracheostomy. We also compared patients who had early
      tracheostomy (less than median time to procedure) with those who had late
      tracheostomy. RESULTS: Of the 2844 admissions (2581 patients), unplanned
      tracheostomy was performed during 461 admissions (16.2%) on 454 patients (17.6%).
      The median time to tracheostomy was 6 days. The ICU, hospital and 1-year
      mortality rates were 10.8, 27.1 and 37.2%, respectively, significantly less than
      those of the group ventilated without tracheostomy. The median time to
      decannulation was 14 days. Patients who had early tracheostomy had a more
      favourable long-term survival than those who had late tracheostomy. No procedure
      related mortality was registered. CONCLUSIONS: In our ICU, having a tracheostomy
      performed was associated with a favourable long-term outcome with regard to
      survival, and early tracheostomy improved survival in addition to consuming less
      ICU resources.

PMID- 16451157
TI  - Myocardial glycerol release, arrhythmias and hemodynamic instability during
      regional ischemia-reperfusion in an open chest pig model.
AB  - BACKGROUND: To develop cardioprotection against peri-operative myocardial
      ischemia-reperfusion injury, we need animal models where the local metabolism and
      blood flow are studied concomitantly with the global circulatory consequences
      during regional coronary occlusion. METHODS: In six anesthetized domestic pigs,
      the largest branch of the circumflex artery was occluded for 30 min.
      Microdialysate was sampled from the ischemic and non-ischemic myocardium along
      with continuous measurements of local coronary artery flow, global hemodynamics
      and registration of arrhythmias, from baseline through to 30 min of ischemia and
      180 min of reperfusion. RESULTS: During ischemia, the microdialysate glucose
      concentration decreased, the glycerol concentration increased and the
      lactate/pyruvate ratio increased significantly. For glycerol, there was a further
      increase at reperfusion. During ischemia, cardiac output was unchanged; however,
      during reperfusion there was a significant drop lasting for several minutes,
      longer than the period in which an increased number of arrhythmias were
      registered. CONCLUSION: The present study demonstrates deranged circulation and
      arrhythmias corresponding to ischemic metabolism after regional myocardial
      ischemia and reperfusion. Reperfusion induced more pronounced circulatory changes
      than the actual ischemia. A substantial increase in myocardial glycerol release
      seems to be a marker of ischemic metabolism and may prove to be an indicator of
      reperfusion injury.

PMID- 16451158
TI  - Effects of intravascular volume therapy using hydroxyethyl starch (130/0.4) on
      post-operative bleeding and transfusion requirements in children undergoing
      cardiac surgery: a randomized clinical trial.
AB  - BACKGROUND: Hydroxyethyl starch (HES) used for intravascular volume expansion may
      cause coagulation abnormalities, especially in cardiac patients. Although low
      molecular weight HES (130/0.4) has been developed to minimize its influence on
      coagulation, experience with HES (130/0.4) in children is limited. Therefore, we
      evaluated the effects of a HES (130/0.4) infusion on post-operative blood loss in
      children undergoing cardiac surgery. METHODS: Forty-two children undergoing
      cardiac surgery were assigned at random to receive either 10 ml/kg fresh frozen
      plasma (FFP group; n=21) or HES (130/0.4) (HES group; n=21) shortly after
      cardiopulmonary bypass termination. Activated partial thromboplastin time (aPTT)
      and international normalization ratio (INR) were measured. In addition, post
      operative transfusion requirements and blood loss until the end of the first post
      operative day were compared. RESULTS: INR was significantly prolonged after HES
      infusion in comparison to the FFP group (P<0.05). During the first 24 h after
      surgery, post-operative blood loss, the use of allogenic blood/blood products and
      aPTT were similar in all children. CONCLUSIONS: Our study shows that the
      administration of a moderate dose of HES (130/0.4) in children undergoing cardiac
      surgery does not cause more bleeding or a higher transfusion requirement than a
      FFP infusion, and suggests that the administration of 10 ml/kg HES (130/0.4) is a
      safe alternative to plasma for intravascular volume replacement in this patient
      population.

PMID- 16451159
TI  - Transarterial block as an addition to a conventional catheter technique improves
      the axillary block.
AB  - BACKGROUND: We have had favourable experience with a triple injection technique,
      combining an axillary catheter technique with a transarterial axillary block.
      This method has been used successfully for routine surgery and re-implantation of
      fingers, hand or forearm. We hypothesized that with this technique, block onset
      time and effectiveness are better than with a conventional catheter technique,
      and designed a study comparing this new technique with a conventional single
      injection through a catheter. METHODS: Fifty-one adult patients were included in
      a prospective study. In all patients, a short axillary plexus catheter was
      positioned close to the median nerve. All patients had an injection through the
      catheter, while 26 of the patients had an additional injection behind, and in
      front of, the axillary artery. Sensory and motor block were tested continuously
      every minute for 29 min. Block success was recorded as onset time to analgesia,
      anaesthesia and complete motor block in the first 29 min. At 30 and 50 min, an
      analgesia block score was recorded. RESULTS: The transarterial injection plus
      catheter method was more effective, with a higher success rate and faster onset,
      than the catheter method. Readiness for surgery with analgesia in the median,
      radial and ulnar nerves was achieved in the catheter group in 13 patients (52%)
      at a mean time of 20.8 min, and in the combined group in 21 patients (81%) at a
      mean time of 13.3 min (P<0.05, P<0.05). At 50 min the situation was 17 (68%) and
      24 (92%), respectively (P<0.05). CONCLUSION: The combined triple injection is
      faster and more effective than the catheter method alone.

PMID- 16451160
TI  - A case of suspected non-neurosurgical adult fatal propofol infusion syndrome.
AB  - A previously healthy woman (20 years old) was admitted to our hospital with
      several fractures after a car accident. She was sedated with propofol, etc. in
      doses ranging from 1.4 to 5.1 mg/kg/h for 88 h. She developed multiple organ
      failure with rhabdomyolysis and died. This case fulfils (except acidosis) the
      criteria of propofol-infusion syndrome (PRIS) in a young adult.

PMID- 16451161
TI  - Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with
      complement 1 (C1) inhibitor concentrate.
AB  - BACKGROUND: Up to seven in every 1000 patients experience angioedema from
      angiotensin-converting enzyme (ACE) inhibitors, even after many years of use. In
      2003, every 20th Norwegian used an ACE inhibitor. CASE REPORT: A 61-year-old
      woman with chronic obstructive pulmonary disease and a past acute myocardial
      infarction had used 7.5 mg of ramipril daily for the past 7 years. She also used
      acetylsalicylic acid, simvastatin, theophylline and salmeterol. One night she
      woke up with edema of the tongue. On hospital arrival, 250 mg of hydrocortisone
      and 5 mg of dexchlorpheniramine were given intravenously (i.v.) and 0.3 mg of
      epinephrine was given subcutaneously (s.c.). The edema of the tongue progressed
      over the next 8 h and made the tongue protrude. Fiberscopy revealed glassy edema
      of the arytenoids. Inspiratory stridor was heard and the patient could not speak.
      She became increasingly uneasy and restless. Berinert complement 1 (C1) inhibitor
      concentrate (1500 units) was administered i.v. Over the following 20 min, stridor
      gradually subsided, the patient calmed and she was able to talk. DISCUSSION: ACE
      inhibitor-provoked angioedema shares many clinical features with hereditary
      angioedema (HAE), including a limited effect of steroids, antihistamines and
      epinephrine. HAE, caused by excess bradykinin formation as a result of C1
      inhibitor deficiency, usually has its laryngeal edema effectively reversed by C1
      inhibitor in less than 0.5 h. Although patients experiencing ACE inhibitor
      provoked angioedema have normal C1 inhibitor values, as in our patient, excess
      bradykinin is probably important as ACE breaks down bradykinin. It is unknown why
      ACE inhibitor-provoked angioedema appears in some and sometimes after many years
      of use. CONCLUSION: We believe that C1 inhibitor was effective in reversing the
      ACE inhibitor-induced angioedema in our patient.

PMID- 16451162
TI  - 'Different concentrations' are more than one.

PMID- 16451163
TI  - Pain and emergence agitation in children.

PMID- 16451165
TI  - Myoglobinemia and propofol infusion.

PMID- 16451167
TI  - Jaw thrust maneuver.

PMID- 16451169
TI  - Validity and new malignant hyperthermia diagnostic procedures.

PMID- 16451170
TI  - Erythropoietin and autologous blood pre-donation.

PMID- 16451172
TI  - Quorum sensing: the many languages of bacteria.
AB  - In the conventional view of prokaryotic existence, bacteria live unicellularly,
      with responses to external stimuli limited to the detection of chemical and
      physical signals of environmental origin. This view of bacteriology is now
      recognized to be overly simplistic, because bacteria communicate with each other
      through small 'hormone-like' organic compounds referred to as autoinducers. These
      bacterial cell-to-cell signaling systems were initially described as mechanisms
      through which bacteria regulate gene expression via cell density and, therefore,
      they have been collectively termed quorum sensing. The functions controlled by
      quorum sensing are varied and reflect the needs of a particular species of
      bacteria to inhabit a given niche. Three major quorum-sensing circuits have been
      described: one used primarily by Gram-negative bacteria, one used primarily by
      Gram-positive bacteria, and one that has been proposed to be universal.

PMID- 16451173
TI  - Pathogenesis of enteroaggregative Escherichia coli infection.
AB  - Enteroaggregative Escherichia coli (EAEC) is emerging as a significant diarrheal
      pathogen in multiple population groups. Although most commonly associated with
      pediatric diarrhea in developing countries, EAEC is also linked to diarrhea in
      adults including HIV-positive patients and travelers and has been a cause of food
      borne outbreaks in the industrialized world. Current data suggest that one set of
      virulence elements is not associated with all EAEC strains, but that combinations
      of multiple factors prevail. Pathogenesis is believed to be initiated with
      adherence to the terminal ileum and colon in an aggregative, stacked-brick-type
      pattern by means of one of several different hydrophobic aggregative adherence
      fimbriae. Some strains of EAEC may then elaborate cytotoxins including the
      plasmid-encoded toxin and the enterotoxins, EAST1 and ShET1. An AraC homolog
      termed AggR regulates several genes contributing to fimbrial biogenesis in
      'typical EAEC strains'. AggR has now also been shown to regulate genes on a
      chromosomal island. Sequencing of the EAEC type strain 042 completed at the
      Sanger Center has revealed two other chromosomal islands that are being explored
      for their pathogenetic potential. This article reviews these virulence elements
      and presents on-going areas of research in EAEC pathogenesis.

PMID- 16451174
TI  - Isolation of a temperature-sensitive dnaA mutant of Staphylococcus aureus.
AB  - Of 750 temperature-sensitive mutants of Gram-positive Staphylococcus aureus, one
      was complemented by the dnaA gene. This mutant had a single base transition in
      the dnaA gene causing the amino-acid substitution mutation, Ala40Thr. Phage
      transduction experiments showed that this temperature-sensitive phenotype was
      linked with a drug-resistant marker inserted near the dnaA gene, suggesting the
      dnaA mutation is responsible for the phenotype. Flow cytometric analysis revealed
      that the dnaA mutant was unable to initiate DNA replication at a restrictive
      temperature and exhibited asynchrony in the replication initiation at a
      permissive temperature. This is the first report of a temperature-sensitive dnaA
      mutant in S. aureus, and the results show that DnaA is required for the
      initiation of chromosomal replication and for the regulation of synchrony in the
      bacterial cells.

PMID- 16451175
TI  - Comparative study of vanA gene transfer from Enterococcus faecium to Enterococcus
      faecalis and to Enterococcus faecium in the intestine of mice.
AB  - Vancomycin-resistant enterococci represent a large reservoir in animals because
      of the use of avoparcin as a growth promoter in Europe. These strains of animal
      origin enter the food chain and can either colonize the human gut or transfer
      their resistance genes to the human microbiota. In this study, we compared the
      transfer of vancomycin resistance from resistant animal Enterococcus faecium to
      sensitive human Enterococcus faecalis and E. faecium. We analysed these transfers
      in dibiotic mice and human faecal flora-associated mice. VanA transfer from
      animal E. faecium to human E. faecalis occurred in dibiotic mice. The
      transconjugants appeared rapidly and persisted at levels between 3.0 and 4.0
      log10 colony-forming units g(-1) of faeces. In human faecal flora-associated
      mice, vanA gene transfer was not detected towards E. faecalis but was possible
      between E. faecium strains. Our experiments revealed the possibility of vanA
      transfer from animal E. faecium to human E. faecalis in vitro and in vivo in the
      intestine of dibiotic mice. However, intraspecies transfer of vanA gene seems
      more common than interspecies transfer among enterococci.

PMID- 16451176
TI  - Attachment of different soil bacteria to arbuscular mycorrhizal fungal
      extraradical hyphae is determined by hyphal vitality and fungal species.
AB  - Attachment of certain bacteria to living arbuscular mycorrhizal fungal
      extraradical hyphae may be an important prerequisite for interactions between
      these microorganisms, with implications for nutrient supply and plant health. The
      attachment of five different strains of gfp-tagged soil bacteria (Paenibacillus
      brasilensis PB177 (pnf8), Bacillus cereus VA1 (pnf8), Pseudomonas fluorescens
      SBW25 :: gfp/lux, Arthrobacter chlorophenolicus A6G, and Paenibacillus peoriae
      BD62 (pnf8)) to vital and nonvital extraradical hyphae of the arbuscular
      mycorrhizal fungi Glomus sp. MUCL 43205 and Glomus intraradices MUCL 43194 was
      examined. Arthrobacter chlorophenolicus did not attach to hyphae, whereas the
      other bacterial strains did to a varying degree. Only P. brasilensis showed
      greater attachment to vital hyphae than nonvital hyphae of both Glomus species
      tested. Pseudomonas fluorescens showed a higher attachment to vital compared with
      nonvital Glomus sp. MUCL 43205 hyphae, whereas this relationship was opposite for
      attachment to G. intraradices. Both B. cereus and P. peoriae showed higher
      attachment to nonvital hyphae. This study provides novel evidence that under
      laboratory conditions soil bacteria differ in their ability to colonize vital and
      nonvital hyphae and that this can also be influenced by the arbuscular
      mycorrhizal fungal species involved. The significance of bacterial attachment to
      mycorrhizal fungal extraradical hyphae is discussed.

PMID- 16451178
TI  - Enterobacter sp. VKGH12 growing with n-butanol as the sole carbon source and
      cells to which the alcohol is added as pure toxin show considerable differences
      in their adaptive responses.
AB  - The solvent-tolerant bacterium Enterobacter sp. VKGH12 is able to grow in toxic
      concentrations of n-butanol up to 1.5 % (volume in volume) as the sole carbon and
      energy source. Morphology changes in the cells growing on increasing
      concentrations of n-butanol were observed. The size of the bacteria decreased
      with increasing concentrations of n-butanol, also leading to an enhanced ratio
      between the surface and volume of the cells. This is in complete contradiction to
      the reaction of glucose-grown cells to which n-butanol had been added as a toxin.
      Similar differences were found in typical adaptive responses to toxic organic
      compounds, namely changes in fatty acid composition of membrane lipids and the
      activity of catalase. In both cases, reactions depending on the n-butanol
      concentrations could be observed when the toxin was added to glucose-grown cells,
      whereas no reaction was observable when the cells were growing in n-butanol as
      the sole carbon and energy source. This is another proof for the observation that
      there are certain differences between the adaptive strategies of cells when
      adapting to high concentrations of a growth substrate and those when adapting to
      a toxin added to growing cells.

PMID- 16451177
TI  - SipA, a novel type of protein from Synechococcus sp. PCC 7942, binds to the
      kinase domain of NblS.
AB  - Cyanobacteria respond to nutrient stress conditions by degrading their light
      harvesting complexes for photosynthesis, a process regulated in Synechococcus sp.
      PCC 7942 by the sensor histidine kinase non-bleaching sensor (NblS). In yeast two
      hybrid screenings for proteins interacting with NblS we have identified a novel
      type of protein, named SipA for NblS interacting protein A. Specific binding
      between NblS and SipA is observed with both yeast and bacterial two-hybrid
      systems. Additional yeast two-hybrid screenings with SipA as bait further
      confirmed the specificity of the interaction and allowed us to map their
      determinants to the ATP-binding domain of NblS. Strong conservation and
      coevolution of both NblS and SipA in cyanobacteria further suggests the
      importance of SipA in the context of the NblS signal transduction network.

PMID- 16451179
TI  - Cloning and characterization of a gene encoding a cold-shock protein in
      Lactobacillus casei.
AB  - One csp-like gene, called cspA, from the lactic acid bacterium Lactobacillus
      casei was identified by an inverse polymerase chain reaction approach based on
      degenerate primers. cspA encodes a protein of 66 amino acid residues, which
      displays at least 74% identity with Csp proteins of Lactobacillus genera.
      Northern blot analysis revealed that cspA is transcribed monocistronically and
      that its expression is induced after a temperature downshift from 37 degrees C to
      20 degrees C. The transcriptional start site has been determined and is situated
      98 bp upstream of the initiation codon. A cspA mutant strain was constructed and
      it showed reduced growth rate compared with the wild type at both optimal and low
      temperatures, demonstrating that CspA plays an important role in the physiology
      of L. casei.

PMID- 16451180
TI  - Identification of a Ferric uptake regulator from Microcystis aeruginosa PCC7806.
AB  - Ferric uptake regulator (Fur) proteins are widely recognized as repressors that
      in many prokaryotes regulate a large number of genes involved in iron homeostasis
      and oxidative stress response. In our study, we were able to identify the
      complete sequence of the fur gene from Microcystis aeruginosa using inverse
      polymerase chain reaction. DNA sequence analysis confirmed the presence of a 183
      amino-acid open reading frame that showed high identity with Fur proteins
      reported for cyanobacteria. The recombinant Fur protein has been purified and
      electrophoretical mobility shift assays shown to be active. Mn2+ and
      dithiothreitol enable Fur to bind to its promoter, with dithiothreitol being more
      potent. The expression of Fur in Microcystis was induced about twofold in iron
      deficient conditions.

PMID- 16451181
TI  - Persistent infection in a dairy herd with an unusual genotype of bovine
      Cryptosporidium parvum.
AB  - On two occasions, we identified Cryptosporidium parvum with an unusual banding
      pattern after restriction enzyme digestion of Cryptosporidium oocyst wall protein
      PCR fragments. The samples originated from a single farm with calf diarrhoea. The
      Cryptosporidium oocyst wall protein PCR fragment sequence revealed a point
      mutation in one of the recognition sites for RsaI. Our subgenotyping showed that
      samples from both samplings shared the same MS1 and GP15 alleles. Analysis of the
      TP14 microsatellite was less sensitive, and results were only obtained from two
      samples. Both had the same allele. This is, to our knowledge, the first
      description of a C. parvum with this Cryptosporidium oocyst wall protein
      genotype. More importantly, the genotype seems to be stable over time since we
      could detect it again among newborn animals almost 1 year after it was first
      identified.

PMID- 16451183
TI  - Modification of the biophysical characteristics of membranes in commensal
      Escherichia coli strains from breast cancer patients.
AB  - Escherichia coli G35 N49 strain, from the gut of breast cancer patients, in
      comparison with the E. coli G35 N61 strain, from the gut of healthy people, shows
      in vitro reduction in growth rates and maximal growth yield. The changes in
      certain membrane characteristics, such as low membrane potential and disturbance
      in intramembrane interaction of H+ -ATPase F0F1 with the TrkA system, indicate a
      dysfunction in ion transport and enzymatic activity. These changes can be
      detected during fermentation and in anaerobic conditions (in the gut, for
      example) and may be influenced by unfavorable conditions in the gut of cancer
      patients.

PMID- 16451182
TI  - Analysis of integrons in clinical isolates of Escherichia coli in China during
      the last six years.
AB  - A multiple PCR for the detection of the integrase genes of the three classes of
      integrons was carried out, and their gene cassettes were characterized in 111
      clinical strains of Escherichia coli isolated in Guangzhou City, China during the
      last 6 years. IntI1 and intI2 genes were detected in 95 isolates (85.6%) and four
      isolates (3.6%), respectively. No intI3 gene was detected. Six different gene
      cassettes were found in these strains, and a high prevalence of dfr and aad genes
      was observed. The E. coli isolates that contained a 1664-bp amplicon of dfrA17
      aadA5 in class 1 integron were found to be phylogenetically unrelated to each
      other by using the enterobacterial repetitive intergenic consensus PCR, as the
      cassette could be transferred to recipient strains, indicating that the gene
      cassettes might be disseminated in the clinical strains by a horizontal gene
      transfer. Therefore, it is important that guidelines for the prudent use of
      antimicrobial agents are adopted and surveillance programs are established.

PMID- 16451184
TI  - LadR, a new PadR-related transcriptional regulator from Listeria monocytogenes,
      negatively regulates the expression of the multidrug efflux pump MdrL.
AB  - The Listeria monocytogenes genome encodes putative multidrug efflux transporters
      but only the MdrL transporter has been partially characterized in the wild-type
      LO28 strain. Here, we show in the LO28 strain, that the expression of MdrL is
      repressed at the transcriptional level, under standard growth conditions, by the
      product of a new gene ladR (lmo1408), and the expression of MdrL is induced in
      the presence of rhodamine. Phylogenetic analysis in related firmicutes shows that
      LadR, conserved in all sequenced Listeria genomes, forms an independent group
      from the large and diverse PadR transcriptional regulator family (PF03551). This
      is the first report of a bacterial multidrug transporter controlled by a member
      of the PadR family.

PMID- 16451185
TI  - Aerobic biodegradation of 4-methylpyridine and 4-ethylpyridine by newly isolated
      Pseudonocardia sp. strain M43.
AB  - A filamentous bacterium capable of utilizing 4-methylpyridine and 4-ethylpyridine
      as the sole source of carbon, nitrogen and energy was isolated from sludge. The
      organism, designated as strain M43, clustered most closely with members of the
      genus Pseudonocardia by 16S rRNA gene sequence analysis. During the degradation
      of 4-methylpyridine and 4-ethylpyridine, c. 60% of nitrogen in the pyridine ring
      was released as ammonia. Metabolite analyses showed that 2-hydroxy-4
      methylpyridine and 2-hydroxy-4-ethylpyridine were transiently accumulated during
      the degradation of 4-methylpyridine and 4-ethylpyridine, respectively. Strain M43
      was also able to degrade pyridine, 3,4-dimethylpyridine, 4-carboxypyridine and 2
      hydroxy-4-methylpyridine. The results indicate that degradation of 4
      methylpyridine and 4-ethylpyridine by strain M43 proceeded via initial
      hydroxylation.

PMID- 16451186
TI  - Assignment of the outer-membrane-subunit-selective domain of the membrane fusion
      protein in the tripartite xenobiotic efflux pump of Pseudomonas aeruginosa.
AB  - Early in vivo experiments revealed that the MexA-MexB dipartite pump unit of
      Pseudomonas aeruginosa conferred drug resistance to the cells, which expressed
      OprM, but not to the OprN-bearing cells. While the MexE-MexF unit interplayed
      with either the outer membrane subunits. Taking advantage of this subunit
      selectivity, we selected the MexA mutant that gained the ability to interplay
      with OprN. Four mutants have been isolated and all showed an amino acid
      substitution (Q116R) in the coiled-coil domain of MexA. The hybrid protein
      bearing the coiled-coil domain of MexA and the remainder domains from MexE
      retained the ability to interplay with OprM, but lost the functional interplay
      with OprN. These results established that the coiled-coil domain of the membrane
      fusion protein is responsible for selecting the compatible outer membrane
      subunit.

PMID- 16451187
TI  - Purification and sequencing of cerein 7B, a novel bacteriocin produced by
      Bacillus cereus Bc7.
AB  - Cerein 7B is a new bacteriocin produced simultaneously with cerein 7A by Bacillus
      cereus Bc7 in liquid brain heart infusion cultures. Both bacteriocins are not
      synergistic. The two peptides have been purified to homogeneity by hydrophobic
      interaction, cation exchange and reverse-phase liquid chromatography. They can be
      distinguished by their N-terminal amino acid sequences N-Gly-Trp-Gly-Asp-Val-Leu
      (7A) and N-Gly-Trp-Trp-Asn-Ser-Trp-Gly-Lys (7B). Pre-cerein 7B is 74 amino acids
      long and contains an 18 aminoacid double-glycine type leader sequence that is
      removed to produce the mature bacteriocin. The leader peptide sequence is related
      to that of sec-independent secretion signals suggesting that cerein 7B belongs to
      class II sec-independent bacteriocins.

PMID- 16451188
TI  - H2 and acetate transfers during xylan fermentation between a butyrate-producing
      xylanolytic species and hydrogenotrophic microorganisms from the human gut.
AB  - The aim of this work was to investigate in vitro interrelationships during xylan
      fermentation between an H2 and butyrate-producing xylanolytic species recently
      isolated in our laboratory from human faeces and identified as Roseburia
      intestinalis and the H2-utilizing acetogen Ruminococcus hydrogenotrophicus or the
      methanogen Methanobrevibacter smithii. H2 transfer between M. smithii or Ru.
      hydrogenotrophicus and the xylanolytic species was evidenced, confirming the
      great potential of these H2-consuming microorganisms to reutilize fermentative H2
      during fibre fermentation in the gut. In addition, acetate transfer was
      demonstrated between the xylanolytic Roseburia sp. and the acetogenic species,
      both metabolites transfers leading to butyric fermentation of oat xylan without
      production of H2.

PMID- 16451189
TI  - Enumeration and detection of acetic acid bacteria by real-time PCR and nested
      PCR.
AB  - Acetic acid bacteria play a negative role in wine making because they increase
      the volatile acidity of wines. They can survive in the various phases of
      alcoholic fermentation and it is very important to control their presence and
      ulterior development. The main objective of the present work is to test fast,
      sensitive and reliable techniques such as real-time PCR (rt-PCR) and nested PCR
      for enumerating and detecting the presence of this bacterial group without
      plating. Primers were designed on the basis of the available 16S rRNA gene
      sequences and tested successfully with reference acetic acid bacteria strains.
      The usefulness of rt-PCR was demonstrated by comparing the results with
      traditional techniques (colony and microscope counting). The results were similar
      with all the techniques. Optimized rt-PCR enabled numbers between 10(7) and 10(1)
      cells mL(-1) to be enumerated, while nested PCR detected less than 10 cells mL(
      1). Although this latter technique cannot be used for enumeration, it has several
      advantages in routine laboratory analysis.

PMID- 16451190
TI  - Comparative study of two typing methods, hsp65 PRA and ITS sequencing, revealed a
      possible evolutionary link between Mycobacterium kansasii type I and II isolates.
AB  - One hundred and ninety-eight clinical isolates of Mycobacterium kansasii
      collected between 2003 and 2004 in Japan were genotyped by PCR and restriction
      enzyme analysis (PRA) and 16S-23S internal transcribed spacer (ITS) sequencing.
      The results demonstrated that clinical isolates of M. kansasii in Japan are
      almost exclusively of the type I PRA genotype, as is the case in other countries.
      Although the results of subtyping using the 16S-23S ITS sequence were generally
      consistent with subtyping using hsp65 PRA, four strains showed a discrepancy
      between the two methods. Sequence analysis of the hsp65, gyrB and 16S rRNA genes
      and the ITS sequence of the four strains suggests that they branched from type II
      and could be considered an ancestral strain of the type I strain. The newly
      recognized strains were designated as intermediate type I.

PMID- 16451191
TI  - Co-operative inhibition by fluoride and zinc of glucosyl transferase production
      and polysaccharide synthesis by mutans streptococci in suspension cultures and
      biofilms.
AB  - Fluoride and zinc, alone or in combination at concentrations of 0.2 mM, inhibited
      production-secretion of glucosyltranferases by Streptococcus mutans UA159 growing
      in suspension cultures. Inhibition did not involve growth inhibition or
      starvation. Fluoride and zinc also inhibited glucan production, especially
      insoluble glucan, in fed-batch biofilms. Inhibition of biofilms appeared to be
      associated with starvation as indicated by markedly decreased ATP pools and
      iodophilic polysaccharide levels in biofilm cells. As insoluble glucans are
      important for virulence of mutans streptococci, the inhibitory actions of
      fluoride and zinc could significantly affect cariogenicity.

PMID- 16451192
TI  - DeoT, a DeoR-type transcriptional regulator of multiple target genes.
AB  - In this study, we investigated the genetic organization and function of
      Escherichia coli yciT, a gene predicted by computational methods to belong to the
      DeoR-type family of transcriptional regulators. We show that transcription of
      yciT (here denoted deoT for deoR-Type) initiates from a promoter located upstream
      of a putative open reading frame (denoted deoL for deoT Leader). We also show
      that DeoT acts as a global regulator, repressing the expression of a number of
      genes involved in a variety of metabolic pathways including transport of maltose,
      fatty acid beta-oxidation and peptide degradation.

PMID- 16451193
TI  - Insights into the role of gp63-like proteins in lower trypanosomatids.
AB  - Any actual understanding of trypanosomatids in general requires a comprehensive
      analysis of the less-specialized species as thorough as our knowledge of the more
      specialized Leishmania and Trypanosoma. In this context, we have shown by
      antibody cross-reactivity that purified extracellular metallopeptidases from
      Phytomonas francai, Crithidia deanei (cured strain) and Crithidia guilhermei
      share common epitopes with the leishmanial gp63. Flow cytometry and fluorescence
      microscopy analyses indicated the presence of gp63-like molecules on the cell
      surface of these lower trypanosomatids. Binding assays with explanted guts of
      Aedes aegypti incubated with purified gp63 and the pretreatment of
      trypanosomatids with anti-gp63 antibodies indicated that the gp63-like molecules
      are involved in the adhesive process of these trypanosomatids to the A. aegypti
      gut wall. In addition, our results indicate for the first time that the gp63-like
      molecule binds to a polypeptide of 50 kDa on the A. aegypti gut epithelium
      extract.

PMID- 16451194
TI  - Identification and comparative analysis of the large subunit mitochondrial
      ribosomal proteins of Neurospora crassa.
AB  - The mitochondrial ribosome (mitoribosome) has highly evolved from its putative
      prokaryotic ancestor and varies considerably from one organism to another. To
      gain further insights into its structural and evolutionary characteristics, we
      have purified and identified individual mitochondrial ribosomal proteins of
      Neurospora crassa by mass spectrometry and compared them with those of the
      budding yeast Saccharomyces cerevisiae. Most of the mitochondrial ribosomal
      proteins of the two fungi are well conserved with each other, although the degree
      of conservation varies to a large extent. One of the N. crassa mitochondrial
      ribosomal proteins was found to be homologous to yeast Mhr1p that is involved in
      homologous DNA recombination and genome maintenance in yeast mitochondria.

PMID- 16451195
TI  - Isolation and analysis of genes specifically expressed during fruiting body
      development in the basidiomycete Flammulina velutipes by fluorescence
      differential display.
AB  - Using fluorescence differential display, cDNAs specifically expressed at the
      primordial stage of fruiting body development were isolated from the
      basidiomycete, Flammulina velutipes. Seventy-five cDNAs were sequenced and
      compared with the amino-acid sequences of proteins in the database by BLASTX
      search. Significant similarity was found for 29 cDNAs coding for proteins with
      known function, GTP-binding protein, growth factor, ubiquitin-proteasome,
      cytochrome P450 and hydrophobin, all of which would be associated with fruiting
      body development. Seventeen cDNAs were not similar to proteins in the database
      and may represent unique genes that play specific roles in the process of
      fruiting in F. velutipes.

PMID- 16451196
TI  - SOCS1: a potent and multifaceted regulator of cytokines and cell-mediated
      inflammation.
AB  - Suppressor of cytokine signalling-1 (SOCS1), as the name implies, is a protein
      that functions as a negative regulator of cytokine signalling. Initially
      characterized for its ability to inhibit JAK phosphorylation and function, SOCS1
      also targets proteins for degradation by the proteosome machinery. The expression
      of SOCS1 can be regulated at the transcription, translation and protein level.
      Despite the broad spectrum of cytokines that can induce SOCS1 expression and/or
      be inhibited by SOCS1 in vitro, the use of genetically modified mice has revealed
      a more specific role for SOCS1 in vivo including a critical role in the
      regulation of IFNgamma signalling. In addition, SOCS1 has a complex role in T
      cell activation, and studies have revealed significant roles for SOCS1 in the
      regulation of IL-4, IL-12 and IL-15 in vivo. Interestingly, SOCS1 action is not
      limited to the regulation of the classical JAK/STAT-signalling pathway, because
      SOCS1 also inhibits cytokines like insulin and toll-like receptor signal
      transduction, neither of which activates the JAK/STAT pathway. Evidence is
      emerging for a role for aberrant SOCS1 expression in human disease, particularly
      in a number of malignancies.

PMID- 16451197
TI  - Monoclonal antibodies to native mouse angiotensin-converting enzyme (CD143): ACE
      expression quantification, lung endothelial cell targeting and gene delivery.
AB  - We demonstrated previously that the monoclonal antibody 9B9 to angiotensin
      converting enzyme (ACE), which accumulates very selectively into the rat lung
      after systemic injection, is a powerful tool for immunotargeting of therapeutic
      agents or genes to the rat lung vascular bed. Bearing in mind a high research and
      therapeutic potential of lung targeting via ACE, we obtained a new set of rat
      monoclonal antibodies to different epitopes of mouse ACE in order to expand this
      approach to mice. Nine new monoclonal antibodies, recognizing epitopes on the N-
      and C-domains of catalytically active mouse ACE, were obtained and examined for
      their efficacy to bind ACE both in vitro and in vivo. This set of monoclonal
      antibodies was proved to be useful for ACE quantification (by flow cytometry and
      cell enzyme-linked immunosorbent assay) on the surface of different mouse ACE
      expressing cells: endothelial cells, monocytes, macrophages, dendritic cells and
      spermatozoa. Moreover, gene delivery into mouse ACE-expressing cells using
      adenoviruses increased 40-fold after redirecting of these viruses to ACE (by
      coating these viruses with anti-ACE monoclonal antibodies). Radiolabelled
      (I(125)) monoclonal antibodies specifically accumulated in the mouse lung after
      systemic injection. Monoclonal antibodies 3G8.17, 4B10.5 and 4B10.17 demonstrated
      the highest level of lung uptake, 40-50% of injected dose, and high selectivity
      of lung uptake. Influence of monoclonal antibodies on ACE shedding was
      negligible, except monoclonal antibody 1D10.11. None of the tested monoclonal
      antibodies inhibited ACE activity in vitro. In conclusion, a new set of rat
      monoclonal antibodies to mouse ACE was obtained suitable to study ACE biology in
      mice and for ACE expression quantification on mouse cells in particular. These
      monoclonal antibodies also demonstrated highly efficient and selective lung
      accumulation and thus has the potential for targeting drugs/genes to the
      pulmonary vasculature in different mouse models of human lung diseases, including
      numerous knockout models.

PMID- 16451199
TI  - HLA-A, HLA-B, and HLA-DRB1 alleles and haplotypes in Naxi and Han populations in
      southwestern China (Yunnan province).
AB  - The frequencies of the human leukocyte antigen alleles HLA-A, HLA-B, and HLA-DRB1
      and the A-B-DRB1, A-B, and B-DRB1 haplotypes were studied in Naxi and Yunnan Han
      populations using polymerase chain reaction (PCR)-sequence-specific amplification
      for alleles A and B and a PCR-microtiter plate hybridization method for the DRB1
      allele. A total of 8 A, 19 B, and 30 DRB1 alleles were found in the Naxi
      population, and 15 A, 21 B, and 36 DRB1 alleles were found in Yunnan Han
      population. The common A-B-DRB1 haplotypes in the Naxi population were A*24-B*15
      DRB1*1202, A*11-B*15-DRB1*0405, A*11-B*15-DRB1*1202, A*11-B*38-DRB1*08032, and
      A*11-B*55-DRB1*0405; the common A-B haplotypes were A*11-B*15, A*11-B*38, and
      A*24-B*15; and the common B-DRB1 haplotypes were B*15-DRB1*1202, B*38-DRB1*08032,
      and B*48-DRB1*1201. In the Yunnan Han population, the common A-B-DRB1 haplotypes
      were A*24-B*15-DRB1*1501, A*24-B*46-DRB1*08032, and A*24-B*15-DRB1*1201; the
      common A-B haplotypes were A*24-B*15, A*24-B*46, and A*34-B*46; and the common B
      DRB1 haplotypes were B*15-DRB1*1501, B*46-DRB1*09012, and B*46-DRB1*1401.
      Phylogenetic tree and principal component analyzes based on HLA-A, HLA-B, and
      DRB1 allele frequencies suggested that the Naxi ethnic group belongs to the
      southern Chinese groups, while the Yunnan Han population is a characteristic
      population located intermediate between northern and southern Chinese groups,
      although they live in the southwest of China.

PMID- 16451198
TI  - HLA class I diversity among rural rainforest inhabitants in Cameroon:
      identification of A*2612-B*4407 haplotype.
AB  - The population distribution of alleles of the classical HLA class I loci in
      Cameroon has not been well studied but is of particular interest given the AIDS
      and malarial epidemics afflicting this population. We investigated the genetic
      diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon.
      Subjects from seven small, isolated, indigenous populations (N = 274) in the
      rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles
      using a polymerase chain reaction/sequence-specific oligonucleotide probe assay
      and sequence analysis. Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and
      HLA-C (N = 21) loci were identified, of which A*2301[allele frequency (AF) =
      12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent
      individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF =
      22.4%) the most common serologically defined groups of alleles. Twenty-six
      (28.9%) alleles with a frequency of less than 1% (AF < 1%), 39 (43%) with a
      frequency of 2.0-15.0% (AF = 2.0-15.0%), three globally uncommon alleles [A*2612
      (AF = 2.0%), B*4016 (AF = 0.7%) and B*4407 (AF = 1.4%)], and the A*2612
      Cw*0701/06/18-B*4407 haplotype (haplotype frequency = 1.3%) were also identified.
      Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and
      HLA-C, respectively. The extensive allelic and haplotypic diversity observed in
      this population may have resulted from varied natural selective pressures on the
      population, as well as intermingling of peoples from multiple origins. Thus, from
      an anthropologic perspective, these data highlight the challenges in T-cell-based
      vaccine development, the identification of allogeneic transplant donors and the
      understanding of infectious disease patterns in different populations.

PMID- 16451200
TI  - Inhibitory effects on HLA-DR1-specific T-cell activation by influenza virus
      haemagglutinin-derived peptides.
AB  - Collagen (CII) 263-272 peptide, an autoantigen in rheumatoid arthritis, is a
      specific human leukocyte antigen (HLA)-DR1/4-binding peptide recognized by T-cell
      receptors (TCR). The affinity of influenza virus haemagglutinin (HA) 306-318
      peptide for the antigen-binding groove of HLA-DR1/4 molecules is higher than that
      of CII263-272. The HLA-DR1/4-binding residues of HA306-318 are located in the
      region 308-317. Altered HA308-317 peptides with substitutions of TCR-contact
      residues may inhibit HLA-DR1/4-specific T-cell activation by blocking the antigen
      binding site of HLA-DR1/4 molecules. To evaluate the role of altered HA308-317
      peptides in HLA-DR1-restricted T-cell activation, we synthesized three altered
      HA308-317 peptides. The specific binding of altered HA308-317 peptides to HLA-DR1
      molecules was examined using flow cytometry. Effects of altered HA308-317
      peptides on HLA-DR1-specific T-cell hybridoma were studied by measuring T-cell
      proliferation and surface expression of CD69 or CD25. The results showed that
      altered HA308-317 peptides were able to bind to HLA-DR1 molecules and competed
      with CII263-272 or wildtype HA308-317 peptide. Compared with wildtype CII263-272
      or HA308-317, altered HA308-317 peptides did not stimulate significant T-cell
      proliferation and CD69 or CD25 expression. Furthermore, the altered HA308-317
      peptides inhibited HLA-DR1-specific T-cell activation induced by CII263-272 or
      wildtype HA308-317 peptide, which may suggest an effective therapeutic strategy
      in inhibition of HLA-DR1-specific T-cell responses in autoimmunity.

PMID- 16451201
TI  - Association of hypothyroid disease in Doberman Pinscher dogs with a rare major
      histocompatibility complex DLA class II haplotype.
AB  - Canine hypothyroid disease is similar to Hashimoto's disease in humans, which has
      been shown to be associated with human major histocompatibility complex (MHC)
      genes. We have collected 27 Doberman Pinschers affected with primary hypothyroid
      disease and compared their MHC class II haplotypes with 129 unaffected Doberman
      Pinschers. Three dog-leucocyte antigen (DLA) genes, DLA-DRB1, DQA1 and DQB1, were
      characterized by sequence-based typing and assigned to haplotypes for each dog.
      One rare haplotype was found at an increased frequency in the affected dogs
      compared to the unaffected dogs (Odds ratio = 2.43, P < 0.02). This haplotype has
      only been found in Doberman Pinschers and Labradors to date.

PMID- 16451202
TI  - Levels of the soluble forms of CD80, CD86, and CD83 are elevated in the synovial
      fluid of rheumatoid arthritis patients.
AB  - The release of soluble forms of CD80 (sCD80), CD86 (sCD86), and CD83 (sCD83)
      provide a potentially powerful immunoregulatory mechanism. We therefore
      investigated the potential presence and relative levels of these molecules in the
      synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA) and
      osteoarthritis (OA). Serum and SF levels were measured by enzyme-linked
      immunosorbent assay. Serum levels of sCD80, sCD86, and sCD83 in RA and OA
      patients were similar to those present in normal donor serum (NDS) and the SF of
      OA patients. In contrast, when compared with NDS and OA SF levels, almost all RA
      SF samples had elevated sCD83 levels (32/35, >0.63 ng/ml) and a substantial
      proportion had elevated sCD80 (13/29, >0.22 ng/ml) or sCD86 (16/33, >2.31 ng/ml)
      levels. Analysis of matched pairs of serum and SF from RA patients demonstrated
      that the SF/serum ratio for sCD80 (95% CI = 1.7-3), sCD86 (95% CI = 1.5-3.1), and
      sCD83 (95% CI = 3.6-7.8) levels was >1 in almost all patients. In conclusion,
      this study shows that the SF from almost all RA patients contain elevated levels
      of sCD83 and the majority of these samples also contain elevated levels of sCD80
      and/or sCD86. These molecules may play a role in modulating immune responses
      within the rheumatoid joint.

PMID- 16451204
TI  - HLA-A and HLA-B distribution in Toto - a vanishing sub-Himalayan tribe of India.
AB  - The frequency of HLA-A and HLA-B locus alleles was studied by using polymerase
      chain reaction-based sequence-specific primer method in a very primitive and
      vanishing sub-Himalayan Indian Tribe, the Toto population of North Bengal. The
      Toto, a Mongoloid tribe with a population size of 1172 reside only in the
      Totopara of Jalpaiguri district of North Bengal. We studied 40 individuals and
      observed some high frequency alleles when compared to other Indian tribal, non
      tribal, and major world populations. Particularly, the frequency of HLA-B14 was
      32.5% in the Toto population, the highest known frequency reported in any
      population in the world. This indigenous tribal population may harbour novel HLA
      alleles and unique haplotypes which extensive HLA genotyping will help to reveal,
      and thus further our understanding of their genetic admixture and migration
      patterns.

PMID- 16451203
TI  - A deletion in exon 3 results in a new HLA-A*01 null allele (A*0115N) in a
      Martinican woman.
AB  - We report the identification of a new HLA-A null allele, HLA-A*0115N. This null
      allele has been identified within the A*01 group by a combination of serological
      and molecular typing [Polymerase chain reaction (PCR) sequence-specific primers,
      PCR sequence-specific oligoprobes and sequence-based typing (SBT)] in a potential
      intrafamilial bone marrow donor from Martinique (French West Indies). To
      characterize this A*01 null allele, we performed DNA typing by PCR-SBT on genomic
      DNA from the beginning of exon 2 (position 84) through the end of the exon 4
      (position 895) and revealed a nucleotide deletion at the end of the exon 3. This
      sole difference between the new allele and the HLA-A*0101 generates a premature
      stop codon (TGA) in the beginning of exon 4. This deletion most likely explains
      the lack of cell surface expression of the encoded protein despite the presence
      of A*01 allele. The absence of correct expression of the antigen on the cell
      surface was confirmed by one-dimensional isoelectric focusing (1D-IEF). To date,
      this is the fourth null allele described within the A*01 group.

PMID- 16451205
TI  - Strategies for evaluating B*18 allelic diversity by sequence-based typing applied
      to studies of a population from Singapore and African-Americans.
AB  - Strategies to resolve B*18 alleles which carry a deletion in intron 1 close to
      the 5' end of exon 2 relative to other HLA-B alleles or a null allele mutation in
      exon 1 and to resolve ambiguities among allele combinations including B*18 are
      described. B*18 allele frequencies from volunteer donors recruited for two
      hematopoietic stem cell registries show the presence of two alleles, B*180101 and
      B*1802, in a population from Singapore and only B*180101 in African-Americans.

PMID- 16451206
TI  - Generation of the B*41 group of alleles as indicated by intron sequences.
AB  - The generation of the B*41 alleles has been analysed using exon 1, intron 1, exon
      2, intron 2 and exon 3 sequences. Results showed that B*4102 may have been
      generated as the first B*41 allele by a recombination mechanism between B*400102
      and B*0801 or B*4201 involving intron 2. B*4101, B*4104 and B*4107 alleles could
      have been generated from B*4102 by a gene conversion event taking three different
      fragments from sequences belonging to intron 2/exon 3 of B*45, B*50 or B*49
      alleles. B*4105 and B*4106 could be generated from B*4101 allele by point
      mutations, and B*4103 generation is unclear due to the lack of intron 2. The
      importance of introns in HLA-B allele polymorphism generation is stressed.

PMID- 16451207
TI  - Intergenic recombination with HLA-C leads to a novel HLA-A*19 allele, HLA-A*2910,
      that is characterized by a functionally inactive amino acid exchange in the loop
      connecting the alpha and alpha domains.
AB  - This report describes the HLA-A*29 allele (A*2910) that has been identified by
      sequence-based typing in an 8-year-old Turkish female with leukaemia during
      search for a family-related stem cell donor. The allele is characterized by a
      nucleotide substitution (Guanine to Adenine) in exon 3 at position 258, leading
      to an amino acid exchange from glutamic acid to lysine at position 177. From
      family analysis and sequence comparison, the HLA-A*2910 allele has arisen from
      intergenic recombination with HLA-C. Structurally, the amino acid exchange at
      position 177 is probably functionally inactive due to the location of this amino
      acid exchange in the loop connecting the alpha(2) and alpha(3) domains.

PMID- 16451208
TI  - The association between HLA class II haplotype with Graves' disease in Thai
      population.
AB  - The distribution of HLA-DRB1, -DQA1 and -DQB1 alleles were analysed in 124
      Graves' disease (GD) patients compared to 124 normal controls in order to
      identify the alleles/haplotypes associated with GD in Thai population. The
      DRB1*1602-DQA1*0102-DQB1*0502 haplotype was significantly increased in GD
      patients (P = 0.0209, OR = 2.55). DRB1*07-DQA1*0201-DQB1*0201 haplotype (P =
      0.039, OR = 0.32) and HLA-DRB1*12-DQA1*0601-DQB1*0301 haplotype (P = 0.0025, OR =
      0.28) were significantly decreased in GD patients. Interestingly, a protective
      DRB1*07 allele in Thai population lacks an arginine at position 74 similar to
      DRB1*0311 (a protective allele in Caucasians). A significant association of
      DRB1*1602-DQA1*0102-DQB1*0502 and HLA-DRB1*12-DQA1*0601-DQB1*0301 alleles and
      haplotypes with GD was recently reported in Korean but not in any Caucasian
      studies. Thus, DRB1*1602 allele and closely linked haplotype, DRB1*1602-DQA1*0102
      DQB1*0502, might serve as a marker for genetic susceptibility to GD in Asian
      population.

PMID- 16451209
TI  - Structural aspect of novel HLA-A*02 allele, A*0286, identified by sequence-based
      typing.

PMID- 16451210
TI  - Description of seven new non-human primate MHC-B alleles.

PMID- 16451212
TI  - Nomenclature for factors of the HLA system, update August 2005.

PMID- 16451211
TI  - Nomenclature for factors of the HLA system, update July 2005.

PMID- 16451213
TI  - Nomenclature for factors of the HLA system, update September 2005.

PMID- 16451215
TI  - Expression of AMPA receptor subunits (GluR1-GluR4) in gonadotrophin-releasing
      hormone neurones of young and middle-aged persistently oestrous rats during the
      steroid-induced luteinising hormone surge.
AB  - Glutamate provides excitatory input to gonadotrophin-releasing hormone (GnRH)
      neurones and elicits a response indicative of AMPA receptors. To determine if and
      which AMPA subunits are expressed by GnRH neurones, we conducted triple-label
      immunohistochemistry and confocal analyses on tissue obtained at 08.00, 12.00,
      16.00 and 20.00 h from young and middle-aged, persistently oestrous (MA-PE) rats
      that were ovariectomised and primed with oestrogen and progesterone to induce a
      luteinising hormone (LH) surge. Each AMPA subunit was found in GnRH neurones, but
      in different patterns across the diurnal cycle, which were influenced by age.
      GluR1 expression increased earlier in young rats and the percentage of Fos
      positive GnRH neurones expressing GluR1 rose significantly and was sustained from
      12.00-16.00 h. GluR1 expression was delayed in MA-PE rats and the percentage of
      Fos-positive GnRH neurones expressing GluR1 peaked at 20.00 h. GluR2 expression
      in GnRH neurones did not change over time and was not affected by age; however,
      the percentage of Fos-positive GnRH neurones expressing GluR2 increased earlier
      and was sustained from 08.00-16.00 h in young rats whereas, in MA-PE rats, this
      percentage peaked at 20.00 h. GluR3 expression also increased earlier in young
      rats and peaked at 12.00 h but was delayed in MA-PE rats and peaked at 20.00 h.
      The number of Fos-positive GnRH neurones that coexpressed GluR3 peaked at 12.00 h
      in young rats but showed little change from 12.00-20.00 h in MA-PE rats. GluR4
      expression was maintained at higher levels at 08.00 and 12.00 h in young rats;
      although the percentage of Fos-positive GnRH neurones expressing GluR4 peaked at
      12.00 h in young rats, it showed little change in MA-PE rats. In summary, our
      data show that a higher proportion of Fos-positive GnRH neurones coexpressed AMPA
      receptor subunits in young rats and the expression, particularly of GluR1 and
      GluR2, was increased and sustained throughout the surge, whereas GluR3 and GluR4
      expression peaked just before. In MA-PE rats, the rate of expression of GluR
      subunits and Fos in GnRH neurones was altered in a manner that may explain the
      delay and attenuation of the LH surge.

PMID- 16451216
TI  - Changes in hypothalamic-pituitary-adrenal function, body temperature, body weight
      and food intake with repeated social stress exposure in rats.
AB  - These present studies aimed to compare changes in hypothalamic-pituitary-adrenal
      (HPA) activity and body temperature in response to acute social defeat, to
      repeated social stress and to novel restraint after repeated stress, as well as
      to assess effects on metabolic parameters by measuring body weight gain and food
      and water intake. We found that social defeat produced a marked increase in both
      adrenocorticotrophic hormone and corticosterone compared to placement in a novel
      cage. Similarly, body temperature was also increased during social defeat and
      during 30 min of recovery from defeat. We then examined the effects of 6 days of
      repeated social stress and observed minimal HPA responses to repeated social
      stress compared to control rats. These neuroendocrine responses were contrasted
      by robust increases in body temperature during stress and during recovery from
      stress during 6 days of repeated stress. However, in response to novel restraint,
      repeatedly stressed rats displayed facilitated body temperature responses
      compared to controls, similar to our previous findings with HPA activity. Food
      intake was increased during the light period during which defeat took place, but
      later intake during the dark period was not affected. Repeated stress decreased
      body weight gain in the dark period but food intake was increased overall during
      the 6 days of repeated stress in the light period. As a result, repeated stress
      increased cumulative food intake during the light period in the stressed rats but
      these relatively small increases in food intake were unable to prevent the
      diminished total weight gain in repeatedly stressed rats. Overall, the results
      demonstrate that, although acute social defeat has similar effects on temperature
      and HPA activity, repeated exposure to social stress has divergent effects on HPA
      activity compared to body temperature and that dampened weight gain produced by
      repeated social stress cannot be fully explained by changes in food intake.

PMID- 16451217
TI  - Influence of oestrogenic compounds on monoamine transporters in rat striatum.
AB  - Oestrogens have been reported to modulate rat membrane (DAT) and vesicular
      (VMAT(2)) dopamine transporters. A recent pilot study of postmenopausal women
      showed that chronic oestrogen replacement therapy increases striatal DAT. In the
      present study, we first investigated whether the oestrogen receptors alpha and
      beta mediate the effects of oestradiol on DAT and VMAT(2). Two days after
      ovariectomy, Sprague-Dawley rats were treated for 2 weeks with oestradiol or
      specific ligands for oestrogen receptor alpha, 4,4',4''-(4-propyl-[1H]-pyrazole
      1,3,5-triyl)trisphenol (PPT) or oestrogen receptor beta, 2,3-bis(4-hydroxyphenyl)
      propionitrile (DPN). Ovariectomy caused a decrease in [(125)I]-3beta-(4
      iodophenyl)-tropane-2beta-carboxylic acid isopropyl ester ([(125)I] RTI-121)
      specific binding to DAT transporters in the middle striatum compared to values
      for intact rats, and this was reversed by oestradiol replacement therapy. DPN,
      but not PPT, mimicked the effect of oestradiol. [(125)I] RTI-121 specific binding
      in the anterior and posterior striatum was not affected by ovariectomy or any of
      the drug treatments. Second, we investigated whether oestradiol increased DAT
      specific binding after a longer period of hormonal withdrawal (a model of
      hormonal withdrawal at menopause) and whether the selective oestrogen receptor
      modulators (SERMs), tamoxifen and raloxifene, could reproduce the oestradiol
      induced increase of [(125)I] RTI-121 specific binding in long-term ovariectomised
      rats. Four months after ovariectomy, Sprague-Dawley rats were treated for 2 weeks
      with oestradiol, tamoxifen or raloxifene, and then killed. Ovariectomy decreased
      [(3)H] RTI-121 specific binding to DAT transporters in the middle striatum
      compared to values for intact rats. Treatment with oestradiol, tamoxifen and
      raloxifene reversed this effect. [(125)I] RTI-121 specific binding in anterior
      and posterior striatum was not affected by ovariectomy or treatment with
      oestrogen receptor ligands. In both experiments, neither ovariectomy nor the
      oestrogenic treatments modulated striatal [(3)H] tetrahydrobenazine specific
      binding to VMAT(2). Overall, these results suggest that oestrogen receptor beta
      mediates the oestradiol-induced increase of striatal DAT and that oestradiol can
      increase DAT density even after long-term steroid withdrawal. The results also
      support the premise that the SERMs tamoxifen and raloxifene exert oestrogenic
      agonist effects in the brain.

PMID- 16451218
TI  - Galanin-like peptide promotes feeding behaviour via activation of orexinergic
      neurones in the rat lateral hypothalamus.
AB  - Galanin-like peptide (GALP) is produced in neurones in the hypothalamic arcuate
      nucleus and is implicated in the neural control of feeding behaviour. Previously,
      we have reported that GALP immunoreactive fibres were in direct contact with
      orexin/hypocretin immunoreactive neurones in the rat lateral hypothalamus using
      double-immunofluorescence. Centrally administered GALP is known to stimulate
      feeding behaviour. However, the target neurones of this action have not been
      clarified. The present study aimed to determine features of the GALP-mediated
      neuronal feeding pathway in rat. Accordingly, at the ultrastructural level, GALP
      immunoreactive axon terminals were found to make synapses on orexin/hypocretin
      immunoreactive cell bodies and dendritic processes in the lateral hypothalamus. c
      Fos immunoreactivity was expressed in orexin/hypocretin-immunoreactive neurones
      but not in melanin concentrating hormone-immunoreactive neurones in the lateral
      hypothalamus at 90 min after the application of GALP by i.c.v. infusion.
      Furthermore, to determine whether GALP regulates feeding behaviour via
      orexin/hypocretin neurones, the feeding behaviour of rats was studied following
      GALP i.c.v. injection with or without anti-orexin A and B immunoglobulin (IgG)
      pretreatment. The anti-orexin IgGs markedly inhibited GALP-induced hyperphagia.
      These results suggest that orexin/hypocretin-containing neurones in the lateral
      hypothalamus are targeted by GALP, and that GALP-induced hyperphagia is mediated
      via orexin/hypocretin neurones in the rat hypothalamus.

PMID- 16451219
TI  - Inhibition of corticotrophin-releasing hormone transcription by inducible cAMP
      early repressor in the hypothalamic cell line, 4B.
AB  - We have shown recently that the rapid decline in corticotrophin-releasing hormone
      (CRH) transcription following activation by stress is associated with induction
      and binding to the CRH promoter of the repressor isoforms of cAMP responsive
      element modulator (CREM), inducible cAMP early repressor (ICER). The ability of
      ICER to inhibit CRH transcription was examined in the hypothalamic cell line, 4B,
      which expresses CRH. Co-transfection of the inhibitory isoforms of CREM, ICER I
      and II and CREMbeta, and CRH promoter-luciferase constructs in 4B cells blunted
      basal and forskolin-stimulated CRH promoter activity, an effect which was
      abolished by mutation of the CRE of the CRH promoter. Western blot analyses and
      electromobility gel-shift and super-shift showed increases in endogenous ICER
      after 3 h of incubation with forskolin. Consistent with an inhibitory effect of
      CREM on CRH transcription, chromatin immunoprecipitation assays in cells
      transfected with ICER I revealed recruitment of CREM by the CRH promoter in
      conjunction with decreases in Pol II association. The study shows that generation
      of ICER following prolonged stimulation with forskolin, or transfection of an
      ICER expression vector in hypothalamic cell lines expressing CRH, is associated
      with CREM binding to the CRH promoter and transcriptional repression. The data
      support the hypothesis that induction of repressor isoforms of CREM is part of an
      intracellular feedback mechanism contributing to the termination of CRH
      transcription during stimulation.

PMID- 16451220
TI  - Regulation of MT melatonin receptor expression in the foetal rat pituitary.
AB  - During development, melatonin receptors are transiently expressed in multiple
      neuroendocrine tissues, suggesting a novel role for melatonin in developmental
      physiology. The best characterised model of melatonin signalling during
      development is the pars distalis of the rat pituitary. However, although many
      studies have characterised the postnatal decline of melatonin receptors in the
      rat pars distalis, the mechanism(s) that time the developmental onset of receptor
      expression during embryogenesis are unknown. Analysis of these mechanisms may
      yield important information regarding the putative role of melatonin in
      neuroendocrine development. Here, we report the expression of MT(1) melatonin
      receptor mRNA in the rat pituitary from embryonic day 15.5 (e15.5). Prior to
      e15.5, the homeodomain transcription factor Msx-1, an inhibitor of cellular
      differentiation, is widely expressed throughout the pituitary. In transient
      transfection experiments, Msx-1 potently inhibited pituitary homeobox-1 (Pitx-1)
      induced MT(1) promoter activity and therefore may represent a key inhibitor of
      MT(1) expression in early pituitary development. During late embryogenesis, MT(1)
      mRNA was expressed in both the ventral and dorsal pituitary. Analysis of a 1.5-kb
      fragment of the rat MT(1) promoter revealed four putative cis-elements for the
      POU domain factor Pit-1, which is associated with mid-dorsal cell lineages.
      Although Pit-1 induced a strong, dose-dependent stimulation of MT(1) promoter
      activity in vitro, dual-labelled in situ hybridisation revealed no colocalisation
      of MT(1) and Pit-1 mRNAs in vivo at e19.5. By contrast, all MT(1) positive cells
      colocalised with alphaGSU and most with betaTSH mRNA. Our data therefore
      implicate the decline of Msx-1 expression as a key event that times the onset of
      melatonin receptor expression to the differentiation of endocrine cells types in
      the developing pituitary gland, and suggest that the melatonin-sensitive cells in
      the embryonic pituitary are primarily Pit-1-independent thyrotrophs in the
      rostral pituitary, with a secondary population of pars distalis gonadotrophs.

PMID- 16451221
TI  - Attenuation of fever at near term: is interleukin-6-STAT3 signalling altered?
AB  - Pregnant rats in late gestation show a reduced fever response after stimulation
      with lipopolysaccharide (LPS). This can result from either an increased action of
      endogenous antipyretics or a reduction in the production or action of endogenous
      pyrogens. Nonpregnant rats given LPS release interleukin (IL)-6, which causes
      nuclear translocation of the signal transducer and activator of transcription 3
      (STAT3) in the vascular organ of the lamina terminalis (OVLT), followed by a
      significant increase in core body temperature. The present study investigated
      whether the reduced fever response in near-term pregnant rats is associated with
      a reduced nuclear STAT3 response. Rats at gestation day 15 (G15), gestation day
      21 (G21, near term) and at lactation day 5 (L5) were injected with LPS (50
      microg/kg, i.p.) or vehicle. Only near-term pregnant rats responded with an
      attenuated body temperature during the fever response. Immunohistological
      analysis indicated no significant difference in nuclear STAT3 in the OVLT of the
      different animal groups 2 h after LPS. Measurement of total and phosphorylated
      STAT3 protein in the OVLT with semiquantitative western blot revealed no
      significant differences of this protein among these immune challenged animal
      groups. IL-6 concentrations were also similar at G15, G21 and L5 2 h after
      injection of LPS. These results lead to the conclusion that the attenuation of
      the fever response at near-term pregnancy is not associated with a reduced amount
      of nuclear STAT3 in the OVLT, indicating a maintained IL-6-STAT3 signalling
      pathway in the OVLT.

PMID- 16451223
TI  - Distinguished senior psychologist forum.

PMID- 16451222
TI  - Cell biology of the ghrelin receptor.
AB  - Ghrelin, a gastric peptide involved in growth hormone release and energy
      homeostasis, is the endogenous ligand of the growth hormone secretagogue receptor
      type 1a (GHS-R1a), a G-protein coupled receptor mainly expressed in the pituitary
      and hypothalamus. This receptor mediates the main ghrelin-stimulated endocrine
      actions and some of the nonendocrine actions. However, a number of nonendocrine
      actions associated with ghrelin appear to be mediated by various GHS-R1a-related
      receptor subtypes, which are widely distributed in the central and peripheral
      tissues. This review summarises data concerning the localisation, regulation and
      function of GHS-R1a, as well as related receptors.

PMID- 16451224
TI  - Prelude to a theme on emotion and gratitude.

PMID- 16451225
TI  - Emotions and interpersonal relationships: toward a person-centered
      conceptualization of emotions and coping.
AB  - This essay describes my theory of emotions. I make a case for studying discrete
      emotions in the context of four processes that represent the central features of
      my theoretical system: appraising, coping, flow of actions and reactions, and
      relational meaning. I explain why coping is a key feature of the emotion process,
      and I discuss issues related to the measurement of coping and the importance of
      understanding coping processes in the context of personality and situational
      demands. I make the argument that emotions are best studied as narratives, and I
      offer one such narrative in the form of a case study to demonstrate how emotions
      can best be understood in the context of an interpersonal relationship and by
      considering individual differences, interpersonal transactions, and relational
      meaning. I conclude this essay with a caution that field specialization may
      interfere with our understanding of emotions and other psychological phenomena,
      and I underscore the virtues of ipsative-normative research designs as a way to
      move closer to a person-centered personality psychology.

PMID- 16451226
TI  - Functional impulsivity and reinforcement sensitivity theory.
AB  - In this article, we attempt to integrate Dickman's (1990) descriptive concept of
      Functional Impulsivity (FI) with Gray's (1970, 1991) Reinforcement Sensitivity
      Theory (RST). Specifically, we consider that FI bears great conceptual similarity
      to Gray's concept of reward-reactivity, which is thought to be caused by the
      combined effects of a Behavioral Activation System (BAS) and Behavioral
      Inhibition System (BIS). In our first study, we examine the construct validity
      and structural correlates of FI. Results indicate that FI is related positively
      to measures of BAS and Extraversion, negatively to measures of BIS and
      Neuroticism, and is separate from Psychoticism and typical trait Impulsivity,
      which Dickman calls Dysfunctional Impulsivity (DI). In our second study, we use a
      go/no-go discrimination task to examine the relationship between FI and response
      bias under conditions of rewarding and punishing feedback. Results indicate that
      FI, along with two measures of BAS, predicted the development of a response bias
      for the rewarded alternative. In comparison, high DI appeared to reflect
      indifference toward either reward or punishment. We consider how these findings
      might reconcile the perspectives of Gray and Dickman and help clarify the broader
      understanding of Impulsivity.

PMID- 16451228
TI  - Discrepancies between implicit and explicit self-esteem: implications for
      narcissism and self-esteem instability.
AB  - There appear to be two forms of high self-esteem: secure high self-esteem (which
      is often linked with psychological health) and fragile high self-esteem (which is
      generally associated with poor psychological adjustment and impaired
      interpersonal relationships). Discrepant high self-esteem is a form of fragile
      self-esteem characterized by high explicit self-esteem and low implicit self
      esteem. The present study examined whether discrepant high self-esteem was
      associated with narcissism and self-esteem instability in an undergraduate
      sample. Using multiple measures of implicit self-esteem, two basic findings
      emerged from the present study. First, participants with discrepant high self
      esteem possessed the highest levels of narcissism. Second, participants with high
      explicit self-esteem and high implicit self-esteem displayed the most stable self
      esteem. Findings are discussed in terms of secure and fragile high self-esteem.

PMID- 16451227
TI  - Religion and unforgivable offenses.
AB  - The value of forgiveness is emphasized in many religions, but little is known
      about how members of distinct religious cultures differ in their views of
      forgiveness. We hypothesized and found that Jews would agree more than
      Protestants that certain offenses are unforgivable and that religious commitment
      would be more negatively correlated with belief in unforgivable offenses among
      Protestants than among Jews (Studies 1 and 2). Dispositional forgiveness
      tendencies did not explain these effects (Studies 1 and 2). In Study 3, Jews were
      more inclined than Protestants to endorse theologically derived reasons for
      unforgivable offenses (i.e., some offenses are too severe to forgive, only
      victims have the right to forgive, and forgiveness requires repentance by the
      perpetrator). Differential endorsement of these reasons for nonforgiveness fully
      mediated Jew-Protestant differences in forgiveness of a plagiarism offense and a
      Holocaust offense.

PMID- 16451229
TI  - An exploration of the influence of dispositional traits and appraisal on coping
      strategies in African American college students.
AB  - This study explored the correlates of self-reported coping strategies from both
      an appraisal (e.g., severity, impact, desirability of the event, as well as
      perceived stress) and a dispositional (e.g., preferred/typical coping style, self
      concept clarity, self-esteem, emotion regulation, problem-solving style, anxiety)
      perspective. Participants were 211 African American undergraduate and graduate
      students from diverse socioeconomic backgrounds. The results indicated that
      dispositional traits (especially problem-solving style) are associated uniquely
      with preferred/typical coping styles. The results also provided modest evidence
      that dispositional traits and subjects' appraisals (e.g., challenge, harm/threat,
      impact) are predictive of subjects' coping strategies in specific ongoing
      stressful situations. The general findings from this study appear to mirror
      research on Caucasian subjects.

PMID- 16451230
TI  - Approach and avoidance social motives and goals.
AB  - It was predicted that approach social motives and goals would be linked to
      outcomes characterized by the presence of positive social features, and avoidance
      social motives and goals would be linked to outcomes characterized by the
      presence of negative social features and that the link between approach motives
      and outcomes would be mediated by different processes than the link between
      avoidance motives and outcomes. These hypotheses were examined in three studies
      (two of them longitudinal) that measured participants' dispositional social
      motives, short-term social goals, and social outcomes (e.g., loneliness).
      Approach motives and goals were reliably associated with less loneliness and more
      satisfaction with social bonds, whereas avoidance motives and goals were reliably
      associated with more loneliness, negative social attitudes, and relationship
      insecurity. Results also suggested that these associations were mediated by
      different processes. Implications for the conceptualization of close
      relationships along these two dimensions are discussed.

PMID- 16451231
TI  - Mother and self-representations: investigating associations with symptomatic
      behavior and academic competence in middle childhood.
AB  - This article reports two studies examining the content and structural aspects of
      maternal and self-representations in middle childhood in two prospective studies
      of 9 to 11-year-old children, their stability over time and interrelations, and
      their contribution to symptomatology and academic functioning. In Study 1
      (N=169), content and structural dimensions of participants' open-ended narratives
      of self and mother were assessed, and their factor structure was replicated
      across two consecutive measurement waves carried out a year apart. In Study 2
      (N=137), using an independent sample, the authors investigated the associations
      of self- and maternal representations with teachers' subsequent reports of
      children's internalizing and externalizing symptomatology and academic
      competence. It was assumed that dimensions of self-representations played a
      mediating role in the prediction of children's symptomatology and competence by
      their maternal representations. Results corroborated the existence of
      interdependent but distinct representations of self and mother in middle
      childhood, as well as the stability over time of the structural and thematic
      aspects within each representation. The content of the self- and maternal
      representations was found to associate with observed symptomatic behavior, while
      their structure associated with children's academic competence. In addition,
      results indicated that self-representation content mediates the association of
      maternal representation content with subsequent symptomatic behavior. Findings
      are discussed in the light of the differentiation and interdependence of self-
      and maternal representations in middle childhood.

PMID- 16451232
TI  - Effects of writing about emotions versus goals on psychological and physical
      health among third-year medical students.
AB  - A randomized, controlled trial compared writing about emotional topics (EMO) to
      writing about goals as the "best possible self" (BPS; after King, 2001) and
      evaluated emotional approach coping, i.e., efforts to cope through processing and
      expressing emotion, as a moderator of writing effects on psychological and
      physical health in 64 third-year medical students. In participants with higher
      baseline hostility, the EMO condition was associated with less hostility at 3
      months compared to the BPS and control conditions. Emotional processing (EP) and
      emotional expression (EE) moderated the effect of experimental condition on
      depressive symptoms at 3 months; high EP/EE participants reported fewer
      depressive symptoms in the EMO condition, whereas low EP/EE individuals reported
      fewer depressive symptoms in the BPS condition compared to the EMO and control
      conditions. A moderating effect of EP on physical health was also identified,
      such that low EP individuals who wrote about goals (BPS) had fewer health care
      visits at 3 months compared to low EP participants in the EMO and control
      conditions.

PMID- 16451234
TI  - Learning in teaching hospitals and the community: time to get the balance right.

PMID- 16451233
TI  - Cloninger's temperament dimensions and threat, stress, and performance appraisals
      during different challenges among young adults.
AB  - We examined the relationship of Cloninger's temperament factors-Novelty Seeking,
      Harm Avoidance, Reward Dependence, and Persistence-to perceived threat and stress
      and performance appraisals during different challenges, i.e., mental arithmetic,
      the reaction time task, and three public speaking tasks, among 97 young adult men
      and women. Temperament was measured by the Temperament and Character Inventory.
      The results showed that, although some of the predictions made by Cloninger's
      model were confirmed, some were unsupported. The results revealed also some
      associations between temperament and cognitive appraisals that were intelligible,
      but not predicted by Cloninger's model. There were considerable domain
      specificity and gender differences in the associations found. Cloninger's
      temperament dimensions are related to threat, stress, and performance appraisals,
      thereby influencing individual's stress vulnerability, adjustment, and personal
      functioning.

PMID- 16451235
TI  - Is there a role for peer review in performance appraisal of medical students?

PMID- 16451236
TI  - Making sense of grounded theory in medical education.
AB  - BACKGROUND: Grounded theory is a research methodology designed to develop,
      through collection and analysis of data that is primarily (but not exclusively)
      qualitative, a well-integrated set of concepts that provide a theoretical
      explanation of a social phenomenon. OBJECTIVE: This paper aims to provide an
      introduction to key features of grounded theory methodology within the context of
      medical education research. OVERVIEW: In this paper we include a discussion of
      the origins of grounded theory, a description of key methodological processes, a
      comment on pitfalls encountered commonly in the application of grounded theory
      research, and a summary of the strengths of grounded theory methodology with
      illustrations from the medical education domain. DISCUSSION: The significant
      strengths of grounded theory that have resulted in its enduring prominence in
      qualitative research include its clearly articulated analytical process and its
      emphasis on the generation of pragmatic theory that is grounded in the data of
      experience. When applied properly and thoughtfully, grounded theory can address
      research questions of significant relevance to the domain of medical education.

PMID- 16451237
TI  - Empirical evidence for symbiotic medical education: a comparative analysis of
      community and tertiary-based programmes.
AB  - BACKGROUND: Flinders University has developed the Parallel Rural Community
      Curriculum (PRCC), a full year clinical curriculum based in rural general
      practice in South Australia. The examination performance of students on this
      course has been shown to be higher than that of their tertiary hospital-based
      peers. AIM: To compare the learning experiences of students in the community
      based programme with those of students in the tertiary hospital in order to
      explain these improved academic outcomes. METHOD: A case study was undertaken,
      using an interpretivist perspective, with 3 structured interviews carried out
      over 2 academic years with each of 6 students from the community-based programme
      and 16 students from the tertiary hospital. The taped interviews were transcribed
      and analysed thematically using NUD*IST software. RESULTS: The community-based
      programme was successful in immersing the students in the clinical environment in
      a meaningful way. Four key themes were found in the data. These represented clear
      differences between the experiences of the community-based and hospital-based
      students. These differences involved: the value that students perceived they were
      given by supervising doctors and their patients; the extent to which the
      student's presence realised a synergy between the work of the university and the
      health service; opportunities for students to meet the aspirations of both the
      community and government policy, and opportunities for students to learn how
      professional expectations can mesh with their own personal values. CONCLUSION:
      This study has provided empirical evidence for the importance of the concept of
      symbiosis in understanding quality in medical education.

PMID- 16451238
TI  - Comparative academic performance of medical students in rural and urban clinical
      settings.
AB  - OBJECTIVE: To determine whether the academic performance of medical students
      learning in rural settings differs from those learning in urban settings. DESIGN:
      Comparison of results of assessment for 2 full cohorts and 1 part cohort of
      medical students learning in rural and urban settings in 2002 (209 students),
      2003 (226 students) and 2004 (220 students), including results for each
      specialist rotation in the 3rd year and end-of-year examinations in the 2nd and
      4th years. SETTING: University of Queensland School of Medicine, Brisbane.
      Students spent the whole 3rd year (of a 4-year graduate entry programme)
      conducting 5 specialist 8-week rotations in either the rural clinical division
      (rural students) or in Brisbane (urban students), all following the same
      curriculum and taking the same examinations. RESULTS: For the 2002 cohort there
      were no statistically significant differences in academic performance between
      rural and urban students. For the 2003 cohort the only significant difference was
      a higher score for rural students in the end of the 4th-year clinical skills
      examination (65.7 versus 62.3%, P = 0.025). For the 2004 cohort, rural students
      scored higher in the 3rd-year mental health rotation (79.3 versus 76.2%, P =
      0.038) and lower in the medicine rotation (65.5 versus 68.6%, P = 0.037).
      CONCLUSION: Academic performance among students studying in rural and urban
      settings is comparable.

PMID- 16451239
TI  - Perceptions of the learning environment in higher specialist training of doctors:
      implications for recruitment and retention.
AB  - INTRODUCTION: Career choice, sense of professional identity and career behaviour
      are influenced, subject to change and capable of development through interaction
      with the learning environment. In this paper workplace learning discourses are
      used to frame ongoing concerns associated with higher specialist training. Data
      from the first stage of a multimethods investigation into recruitment into and
      retention in specialties in the West Midlands is used to consider some possible
      effects of the specialist learning environment on recruitment and retention.
      METHODS: The aim of the study was to identify issues, through interviews with 6
      consultants and questionnaires completed by specialist registrars from
      specialties representing a range of recruitment levels. These would inform
      subsequent study of attributes and dispositions relevant to specialist practice
      and recruitment. The data were analysed using NVivo software for qualitative data
      management. RESULTS: Participants' perceptions are presented as bipolar
      dimensions, associated with: curriculum structure, learning relationships,
      assessment of learning, and learning climate. They demonstrate ongoing struggle
      between different models of workplace learning. CONCLUSION: Changes in the
      postgraduate education of doctors seem set to continue well into the future. How
      these are reflected in the balance between workplace learning models, and how
      they influence doctors' sense of identity as specialists suggests a useful basis
      for examination of career satisfaction and recruitment to specialties.

PMID- 16451240
TI  - Analysis of verbal interactions in tutorial groups: a process study.
AB  - INTRODUCTION: Collaborative learning, including problem-based learning (PBL), is
      a powerful learning method. Group interaction plays a crucial role in stimulating
      student learning. However, few studies on learning processes in medical education
      have examined group interactions. Most studies on collaboration within PBL used
      self-reported data rather than observational data. We investigated the following
      types of interactions in PBL tutorial groups: learning-oriented interactions
      (exploratory questioning, cumulative reasoning and handling conflicts about
      knowledge); procedural interactions, and irrelevant/off-task interactions. AIM:
      The central question concerned how much time is spent on the different types of
      interaction during group sessions and how the types of interaction are
      distributed over the meeting. METHOD: Four tutorial group sessions in Year 2 of
      the PBL undergraduate curriculum of Maastricht Medical School were videotaped and
      analysed. The sessions concerned the reporting phase of the PBL process. We
      analysed the interactions using a coding scheme distinguishing several verbal
      interaction types, such as questions, arguments and evaluations. RESULTS:
      Learning-orientated interactions accounted for 80% of the interactions, with
      cumulative reasoning, exploratory questioning and handling conflicts about
      knowledge accounting for about 63%, 10% and 7% of the interactions, respectively.
      Exploratory questioning often preceded cumulative reasoning. Both types occurred
      throughout the meeting. Handling conflicts mainly occurred after the first 20
      minutes. CONCLUSIONS: Task involvement in the tutorial groups was high. All types
      of learning-orientated interactions were observed. Relatively little time was
      spent on exploratory questions and handling conflicts about knowledge. Problem
      based learning training should pay special attention to stimulating discussion
      about contradictory information.

PMID- 16451241
TI  - Multi-dimensional profiling of medical students' cognitive models about learning.
AB  - INTRODUCTION: In current constructivist paradigms, learners' previous subject
      matter knowledge, or cognitive models, provide the foundations for the
      construction of new knowledge. Learners' cognitive models about learning also
      mediate students' capacities to learn in their chosen topics of study. The
      diverse backgrounds of students entering medicine suggest that they might come to
      medical studies equipped with a wide variety of cognitive models about learning.
      Some current theories tend to reduce students' cognitions about learning to
      parsimonious representations, such as surface-deep approaches or mastery
      performance goals. It is possible that such reduced representations
      underrepresent, or misrepresent, the complexity of students' cognitive models
      about learning. Good quality teaching needs to take account of learners'
      cognitive models, not just about subject matter, but also about learning. This
      study investigated the diversity and complexity of medical students' cognitive
      models about learning. METHODS: A total of 7 graduate entry, clinical-year
      medical students volunteered for in-depth interviews about learning. NUD*IST text
      analysis software and correspondence analysis were employed to identify
      dimensions and to profile students' responses. RESULTS: The correspondence
      analysis identified a significant 4-dimensional solution that illustrates the
      contributions of multiple variables to students' cognitive models about learning.
      Individual profiles highlight diversity between participants. DISCUSSION: This
      study provides evidence that students' cognitive models about learning are
      complex and highly differentiated. Representations of what students know about
      learning need to take account of such complexity in order to inform instructional
      practice more adequately.

PMID- 16451242
TI  - The acquisition of tacit knowledge in medical education: learning by doing.
AB  - AIM: This study was designed to assess medical school teachers' tacit knowledge
      of basic pedagogic principles and to explore the specific character of the
      knowledge base. METHODS: We developed a 50-item, multiple-choice question test
      based on important pedagogic principles, and classified all questions as
      requiring either declarative or procedural knowledge. A total of 72 medical
      teachers representing 5 different groups of clinicians and educators agreed to
      sit the test. RESULTS: Teachers in all 5 groups performed well on the test of
      tacit pedagogic knowledge but those with advanced education degrees, or local
      recognition as experts, performed best. All test takers performed best on
      questions requiring procedural knowledge. CONCLUSION: Medical teachers possess
      tacit knowledge of basic pedagogic principles. Superior test performance on
      questions requiring procedural knowledge is consistent with their working in a
      clinical environment characterised by repeated procedural activities.

PMID- 16451243
TI  - Broadening conceptions of learning in medical education: the message from
      teamworking.
AB  - BACKGROUND: There is a mismatch between the broad range of learning theories
      offered in the wider education literature and a relatively narrow range of
      theories privileged in the medical education literature. The latter are usually
      described under the heading of 'adult learning theory'. METHODS: This paper
      critically addresses the limitations of the current dominant learning theories
      informing medical education. An argument is made that such theories, which
      address how an individual learns, fail to explain how learning occurs in dynamic,
      complex and unstable systems such as fluid clinical teams. RESULTS: Models of
      learning that take into account distributed knowing, learning through time as
      well as space, and the complexity of a learning environment including
      relationships between persons and artefacts, are more powerful in explaining and
      predicting how learning occurs in clinical teams. Learning theories may be
      privileged for ideological reasons, such as medicine's concern with autonomy.
      CONCLUSIONS: Where an increasing amount of medical education occurs in workplace
      contexts, sociocultural learning theories offer a best-fit exploration and
      explanation of such learning. We need to continue to develop testable models of
      learning that inform safe work practice. One type of learning theory will not
      inform all practice contexts and we need to think about a range of fit-for
      purpose theories that are testable in practice. Exciting current developments
      include dynamicist models of learning drawing on complexity theory.

PMID- 16451244
TI  - Follow the patient: process and outcome evaluation of medical students'
      educational experiences accompanying outpatients.
AB  - BACKGROUND: To instill patient-centred attitudes in medical students, several
      medical schools in Japan have recently started to offer educational experiences
      in which medical students accompany outpatients throughout entire visits to
      hospitals. OBJECTIVE: To evaluate the processes and outcomes of the educational
      experience of Year 5 medical students accompanying outpatients at Nagoya
      University Hospital. METHODS: An integrated, multimethod approach was adopted
      using a written survey with open-ended questions for students, focus groups with
      students, and a written evaluation survey for patients. In all, 99 students
      completed the survey, 19 students participated in 3 focus groups, and 46 patients
      participated in the evaluation. RESULTS: Many students were sceptical about the
      objectives of the exercise. We were able to gain insight into student perceptions
      about facets of the exercise such as the ratio of students to patients and
      whether or not students should wear white coats. In particular, there was
      consensus among students about the importance of the debriefing session after the
      experience. Students achieved different learning outcomes depending on their
      particular individual experiences. In the student survey, 49% were satisfied with
      this experience, 6% were dissatisfied, and 43% were neither. In contrast,
      patients were highly satisfied with the experience (mean score 4.2 out of 5.0 on
      a Likert scale). Some students expressed concern about being a burden to
      patients, while many patients reported feeling emotionally supported by being
      accompanied by students. CONCLUSION: An integrated approach to programme
      evaluation, using quantitative and qualitative methods, was useful in the process
      and outcome evaluation of this new educational experience. The results have been
      taken into consideration for quality improvement of this curricular element.

PMID- 16451245
TI  - Setting school-level outcome standards.
AB  - BACKGROUND: To establish international standards for medical schools, an
      appropriate panel of experts must decide on performance standards. A pilot test
      of such standards was set in the context of a multidimensional (multiple-choice
      question examination, objective structured clinical examination, faculty
      observation) examination at 8 leading schools in China. METHODS: A group of 16
      medical education leaders from a broad array of countries met over a 3-day
      period. These individuals considered competency domains, examination items, and
      the percentage of students who could fall below a cut-off score if the school was
      still to be considered as meeting competencies. This 2-step process started with
      a discussion of the borderline school and the relative difficulty of a borderline
      school in achieving acceptable standards in a given competency domain. Committee
      members then estimated the percentage of students falling below the standard that
      is tolerable at a borderline school and were allowed to revise their ratings
      after viewing pilot data. RESULTS: Tolerable failure rates ranged from 10% to 26%
      across competency domains and examination types. As with other standard-setting
      exercises, standard deviations from initial to final estimates of the tolerable
      failure rates fell, but the cut-off scores did not change significantly. Final,
      but not initial cut-off scores were correlated with student failure rates (r =
      0.59, P = 0.03). DISCUSSION: This paper describes a method to set school-level
      outcome standards at an international level based on prior established standard
      setting methods. Further refinement of this process and validation using other
      examinations in other countries will be needed to achieve accurate international
      standards.

PMID- 16451246
TI  - Not knowing that they do not know: self-assessment accuracy of third-year medical
      students.
AB  - PURPOSE: The development of self-regulated learning is a major focus of our
      problem-based learning (PBL) medical programme. Students who are unsuccessful in
      assessments often seem to lack insight into the standard of their own
      performance, yet the ability to self-assess accurately is essential for the
      effective self-management of learning. The aim of this project was to evaluate
      the accuracy of self- and peer-assessment according to academic performance.
      METHOD: In 2004, 175 3rd-year students undertook an integrated, case-based, short
      essay, formative assessment. After the assessment they were provided with model
      answers and marking criteria. Students marked their own assessment paper and the
      paper of one of their peers. Assessment papers were subsequently marked by
      faculty members. The following data was available for each student: self-mark,
      faculty-mark, score awarded by a peer and the score that they awarded to their
      peer. Self-assessment and peer-assessment ability was compared to overall
      academic performance. RESULTS: Low-achieving students score themselves and their
      peers generously. High-achieving students score themselves more harshly than
      faculty. However, they score their peers accurately. CONCLUSION: In the 3rd year
      of the programme low-achieving students are unable to assess accurately the
      quality of their own work or the work of their peers in a formative written
      assessment. The PBL curriculum does not guarantee the appropriate development of
      self-assessment skills.

PMID- 16451247
TI  - The relationship between professional behaviour grades and tutor performance
      ratings in problem-based learning.
AB  - PURPOSE: We investigated the influence of harsh grading by tutors on tutor
      performance rating by students. METHODS: A total of 187 tutors assessed students'
      professional behaviour in tutorial groups. Students rated tutor performance after
      receiving their grades for professional behaviour. In addition, students were
      asked to indicate whether they perceived their professional behaviour grades as
      too positive, adequate or too negative. This was considered to reflect tutors'
      harshness of grading. Students also rated the quality of the feedback they
      received from tutors with respect to their grades. RESULTS: Professional
      behaviour grades that students perceived as too negative, adequate or too
      positive were associated with tutor performance ratings of 7.4 (SD = 0.9, scale 1
      10, n = 33), 7.7 (SD = 0.9, scale 1-10, n = 95) and 7.5 (SD = 0.8, scale 1-10, n
      = 59), respectively. Harshness of grading did not influence tutor performance
      ratings significantly. Tutor ratings were predicted more effectively by the
      quality of the feedback tutors provided on grades than by the harshness of
      grading. CONCLUSIONS: Tutor performance ratings were not related significantly to
      harshness of grading. Two explanations can be given: (1) tutor performance
      ratings were based on rating by groups of students and (2) the percentage of
      tutors who rated students' professional behaviour as unsatisfactory was low. The
      strong relationship between tutor performance ratings and the adequacy of the
      feedback given by tutors suggests that the tutor performance ratings collected in
      this study are a valid measure of the quality of their teaching, although, for a
      full picture of teaching quality, more measures will be needed.

PMID- 16451248
TI  - Medical students and literature: are we expecting too much?

PMID- 16451249
TI  - Quest for limbal stem cells.

PMID- 16451250
TI  - Resisting susceptibility: bacterial keratitis and generations of antibiotics.

PMID- 16451251
TI  - Changing from Snellen to LogMAR: debate or delay?
AB  - Visual acuity is the most commonly used test to assess visual function. The
      Snellen chart is the universally accepted tool for testing visual acuity despite
      its poor reliability and reproducibility. Newer logMAR charts are now available
      that have negated the disadvantages of the Snellen chart. However, these charts
      are not being used regularly in daily practice. This article discusses the
      reasons for the delayed acceptance of the logMAR chart.

PMID- 16451252
TI  - Awareness of and compliance with recommended dietary supplement among age-related
      macular degeneration patients.
AB  - BACKGROUND: The age-related eye disease study suggested that taking zinc and anti
      oxidants supplements could reduce the progression of age-related macular
      degeneration (AMD). In Australia, the available supplement is Macu-Vision. The
      study aimed to assess the awareness of and compliance with taking this supplement
      and the public health implication. METHODS: The fundus photograph database of
      patients aged 55 years and older at the ophthalmology department of a public
      teaching hospital in Adelaide, Australia was reviewed. In total, 125 patients
      with category 3 and 4 AMD were identified. A total of 100 patients participated
      in this cross-sectional study. RESULTS: In total, 53% of participants were aware
      of the availability of the formulae available in Australia, 38% were taking the
      supplement and only 1% were taking the correct dose. Of those taking the
      supplement 95% (36/38) were taking half the recommended dosage. Among those who
      were aware of the supplement but not taking it, cost was the most common reason
      (31%). Another 31% were not taking it because of actual side-effects experienced,
      fear of potential side-effect and/or fear of interaction with other medications.
      There was no predictive factor for failing to take the formulae available in
      Australia among age, sex, smoking status, living arrangement and category of AMD.
      CONCLUSIONS: Clinicians need to emphasize that the recommended dosage is twice
      that on the supplement label. If the trend demonstrated here of underutilizing
      the formulae available in Australia among public hospital patients continues, it
      is unlikely to have any major public health impact in similar settings in
      Australia.

PMID- 16451253
TI  - Glaucomatous damage in normotensive fellow eyes of patients with unilateral
      hypertensive pseudoexfoliation glaucoma: normotensive pseudoexfoliation glaucoma?
AB  - BACKGROUND: The objective of the study was to investigate the prevalence of
      glaucomatous damage in normotensive fellow eyes of patients with unilateral high
      tension pseudoexfoliation (PX) glaucoma. METHODS: Initial examination records of
      111 patients with unilateral PX glaucoma with intraocular pressure (IOP) > or =
      22 mmHg in the hypertensive eye and IOP < or = 21 mmHg in the normotensive fellow
      eye without any prior antiglaucomatous treatment were retrospectively studied.
      Visual field and optic disc examination results were evaluated for glaucomatous
      damage in the normotensive eyes. RESULTS: Glaucomatous changes were detected in
      45 of the 111 fellow eyes (40%). The damage was mild in 25 eyes (22%), moderate
      in 18 eyes (16%), and severe in 2 (2%). The factors significantly associated with
      glaucomatous findings in the normotensive eyes were clinical detection of PX,
      higher age (> or =70 years), higher maximal IOP (> or =18 mmHg) and wider IOP
      fluctuation (> or =6 mmHg) in the univariate analyses. In the multivariate
      analysis, associated factors remained as higher maximal IOP (odds ratio = 7.92,
      confidence interval = 2.82-22.23, P < 0.001) and wider IOP fluctuation (odds
      ratio = 5.67, confidence interval = 2.05-15.74, P = 0.001). CONCLUSION:
      Normotensive fellow eyes of patients with unilateral high-tension PX glaucoma are
      under significant risk of glaucomatous damage, related with the level and the
      fluctuation range of IOP.

PMID- 16451254
TI  - Progression of visual field loss in open angle glaucoma in the Melbourne Visual
      Impairment Project.
AB  - PURPOSE: To quantify the progression of visual field loss in participants with
      open angle glaucoma. METHODS: Cluster random samples of 3271 participants
      participated in this study. Each participant underwent a standardized ophthalmic
      examination, which included intraocular pressure measurement, Humphrey 24-2
      Fastpac visual field testing and stereophotography of the optic disc. At baseline
      118 participants were identified as possible, probable or definite open angle
      glaucoma and 74 (62.7%) of these were seen again at the follow-up examination.
      Progression of visual field loss was defined using three methods: the Advanced
      Glaucoma Intervention Study criteria, the modified Anderson criteria and the
      Blumenthal method. RESULTS: In total, 49% of subjects showed progressive visual
      field loss with at least one method. The Blumenthal criteria yielded the highest
      rate of progression (37%), followed by the modified Anderson method (33%) and the
      Advanced Glaucoma Intervention Study method (16%). The progressive visual field
      loss was associated with baseline glaucoma status (P = 0.02); 65% of the definite
      glaucoma progressed, compared with 57% of the probable glaucoma and 25% of the
      possible glaucoma. Participants who had been previously diagnosed with glaucoma
      had a higher rate of progression (54%) when compared with those who had not been
      diagnosed previously (47%). In total, 50% (four of eight) of those receiving
      glaucoma medication at baseline had progressive visual field loss; all were in
      the definite glaucoma category. CONCLUSION: Despite use of glaucoma medications
      the majority of glaucoma patients managed by their regular ophthalmologist
      experienced progressive visual field loss over a 5-year period.

PMID- 16451255
TI  - Intravitreal triamcinolone injection for chronic diffuse diabetic macular oedema.
AB  - PURPOSE: To determine the efficacy and safety of intravitreal triamcinolone in
      chronic diffuse diabetic macular oedema. METHODS: This prospective,
      interventional consecutive case series study consisted of 59 eyes (36 patients)
      with chronic diffuse diabetic macular oedema, which received an intravitreal
      injection of 4 mg triamcinolone acetonide. The results were evaluated by clinical
      examination and fluorescein angiography. Potential complications such as a rise
      in intraocular pressure, cataract progression and endophthalmitis were recorded.
      RESULTS: All patients completed at least 6 months follow up. The mean visual
      acuity improved significantly from 0.17 +/- 3.4 to a maximum of 0.30 +/- 3.3 at
      the third postinjection month (P < 0.01). Mean improvements in visual acuity
      measured were 2.15 +/- 1.66, 2.42 +/- 2.66, 1.13 +/- 2.74, 0.96 +/- 2.01 and 0.08
      +/- 2.34 lines at the 1, 3, 6, 9 and 12 months follow-up intervals, respectively.
      In all eyes in fluorescein angiography, macular oedema was resolved (63%) or
      decreased (37%) during the follow up. However, the macular oedema reached the
      pretreatment level in 29 (49%) of the eyes at 6 months and 15 of 21 eyes (71%) at
      9 months after injection. Intraocular pressure exceeded 21 mmHg in 10 eyes, which
      were controlled by topical medication. Four eyes showed cataract progression.
      Endophthalmitis was not observed in any of the eyes. CONCLUSIONS: Intravitreal
      injection of 4 mg triamcinolone acetonide appears to be an effective and
      relatively safe therapeutic method for diffuse diabetic macular oedema. Further
      studies are warranted to assess the long-term efficacy, safety and the need for
      reinjection.

PMID- 16451256
TI  - Fluorescein angiography and adverse drug reactions revisited: the Lions Eye
      experience.
AB  - BACKGROUND: The last major survey of adverse reactions to intravenous fluorescein
      angiography was performed more than 20 years ago. There have been two recent
      fatalities involving intravenous fluorescein in Australia. It is important to
      review the current incidence of adverse reactions and latest literature on the
      pathogenesis, prophylaxis and alternatives to intravenous fluorescein
      angiography. METHODS: A retrospective review of all adverse reactions to
      intravenous sodium fluorescein in patients undergoing fluorescein angiography
      between June 1998 and June 2004 was undertaken. The total number of fluorescein
      angiograms performed and the number of patients with adverse reactions were
      identified from the photographic department database and the fluorescein adverse
      reaction register at the Lions Eye Institute. RESULTS: A total of 11 898
      fluorescein angiograms were performed during the study period. There were 132
      adverse reactions recorded. The commonest adverse reactions were nausea and
      vomiting. There were no serious adverse reactions or deaths recorded. There was a
      statistically significant difference in the incidence of adverse reactions
      between sodium fluorescein used from two manufacturers. CONCLUSIONS: Fluorescein
      angiography is a relative safe procedure and comparable to other intravenous
      radiocontrast media angiography or investigation. The present results are
      consistent with previous studies. Prophylactic treatment, fluorescein
      desensitization or oral fluorescein angiography should be considered in high-risk
      patients. Safe guards should be in place to manage potential serious adverse
      reactions. Other imaging techniques, like optical coherence tomography, should be
      considered as an alternative in selected cases.

PMID- 16451257
TI  - National survey on the management of lacrimal canalicular injury in the United
      Kingdom.
AB  - PURPOSE: The management of lacrimal canalicular injury is controversial. It is
      believed that practice varies widely among surgeons. METHODS: One hundred and
      twenty National Health Service-based Consultant Ophthalmologists with
      oculoplastic interest across the United Kingdom (UK) were identified via the
      website http://www.specialistinfo.com, which is a website that asks UK
      consultants to identify their areas of subspecialty interests. Questionnaires
      were sent out to them to determine caseload, intraoperative techniques
      (magnification, suture and stents) and postoperative management (antibiotic use,
      stent placement and replacement and secondary lacrimal surgery) of patients with
      canalicular injuries. RESULTS: Eighty-nine (74%) completed questionnaires were
      returned and analysed. Most (63%) of the respondents treated between one and five
      canalicular injuries over the past year. Thirty-eight (43%) of them would repair
      a monocanalicular injury only if the lower canaliculus was involved and 36 (40%)
      respondents would always repair a monocanalicular injury. Eighty-two (92%)
      respondents used magnification during surgery. Fifty-one (57%) respondents would
      never consider using the pigtail probe. Eighty-five (96%) would use the bubble
      test and/or fluorescein dye to locate the severed medial canalicular end. Vicryl
      or dexon was the suture of choice for 76 (85%) and 63 (71%) respondents for
      repairing pericanalicular and canalicular tissues, respectively. Thirteen (14.6%)
      respondents did not stent their canalicular repairs. Forty-seven (53%) routinely
      used prophylactic antibiotics. Sixty-eight (76%) respondents would wait between 3
      and 12 months before undertaking further lacrimal surgery. CONCLUSION: This study
      confirmed that management of lacrimal canalicular injury varies widely among
      surgeons in the UK.

PMID- 16451258
TI  - Bacteria commonly isolated from keratitis specimens retain antibiotic
      susceptibility to fluoroquinolones and gentamicin plus cephalothin.
AB  - PURPOSE: Patients presenting with presumed infective keratitis were studied to
      determine predisposing factors, the current susceptibilities of the bacterial
      isolates to a range of relevant antibiotics, the success rate of topical
      antibiotic treatment of keratitis and predictors of failure of topical therapy.
      METHODS: Corneal scrapings taken from patients who presented between January 2002
      and December 2003 to the Sydney Eye Hospital Emergency Department with keratitis
      were cultured. The minimum inhibitory concentration of selected antibiotics was
      determined for each bacterial isolate using an agar dilution technique. RESULTS:
      One hundred and twelve consecutive patients presented with corneal ulcers. Forty
      seven of the 112 (42%) patients had a growth from the corneal scraping. Potential
      predisposing factors were identified in 64% of patients, most frequently contact
      lens wear (36% of patients). Coagulase-negative staphylococci were the most
      common species isolated. Other common organisms isolated include Pseudomonas
      aeruginosa, Corynebacterium spp., Staphylococcus aureus and Streptococcus spp.
      CONCLUSIONS: Most microorganisms isolated from patients with bacterial keratitis
      showed susceptibility to ciprofloxacin and aminoglycosides. Cephalothin plus
      aminoglycoside constituted an effective initial broad-spectrum antibiotic
      combination. The success rate of topical antibiotic treatment of corneal abscess
      is 89%. Predictors of failure include older age group, medium or large ulcer,
      culture-negative keratitis, hypopyon and poor visual acuity.

PMID- 16451259
TI  - Wegener's granulomatosis presenting with painless bulbar-conjunctival ulcer and
      central retinal artery occlusion.
AB  - Herein an unusual case of Wegener's granulomatosis with a painless, bulbar
      conjunctival ulcer in the right eye is reported. Rapid disease progression
      occurred with central retinal artery occlusion in the fellow eye. Biopsy of the
      diseased conjunctiva confirmed the clinical diagnosis. The clinical and
      histopathological findings are discussed.

PMID- 16451260
TI  - Possible role of excitotoxicity in the pathogenesis of glaucoma.
AB  - Excitotoxicity describes the process of neuronal injury by excess stimulation of
      amino acid receptors. This form of insult was first described in the retina, and
      subsequently has been shown to be an important component of the pathogenesis of
      ischaemic and traumatic injury in the central nervous system. Furthermore, there
      is increasing evidence that excitotoxicity is involved in several chronic
      neurological conditions, and anti-excitotoxic treatment has already been approved
      for some of these conditions. A large-scale trial is currently underway that will
      determine the efficacy of an anti-excitotoxic drug (memantine) in the management
      of glaucoma. This review provides an overview of neurotransmission and the
      mechanisms of excitotoxicity. The evidence for excitotoxicity as a component of
      certain neurological diseases, including glaucoma, is discussed.

PMID- 16451261
TI  - Limbal stem cells: the search for a marker.
AB  - The corneal epithelium is a self-renewing tissue and must, by definition, have a
      resident basal cell population necessary for homeostasis and wound healing. There
      is a substantial body of evidence, both experimental and clinical, pointing to
      the basal cells of the limbus as the location of corneal epithelial stem cells.
      However, in the absence of a definitive marker of limbal stem cells, the evidence
      remains largely circumstantial. Many markers such as p63 and integrin alpha9 are
      preferentially localized to the limbus but cannot be regarded as stem cell
      specific. Other markers such as K3 and connexin 43 can be regarded as markers of
      corneal differentiation. The discovery of stem cell markers in other organ
      systems, such as the haematopoietic system, offers optimism that a marker of
      limbal stem cells will one day be found. Such a discovery will have far-reaching
      implications for the study of ocular surface biology and stratified squamous
      epithelia in general.

PMID- 16451262
TI  - Unsual ocular metastasis from breast cancer.
AB  - Herein a clinical case of an unusual metastasis from breast cancer to the retina
      and vitreous confirmed by diagnostic vitrectomy is described. Further
      investigation also demonstrated the central nervous system metastasis.

PMID- 16451263
TI  - Idiopathic sclerochoroidal calcification in a 79-year-old woman.
AB  - Sclerochoroidal calcification is an uncommon ocular condition usually seen in
      elderly patients. Lesions are typically bilateral and observed in the mid
      peripheral fundus, frequently near the superotemporal arcade. It is often an
      incidental finding, observed as multiple ill-defined, elevated yellow plaque-like
      lesions, in otherwise asymptomatic patients.

PMID- 16451264
TI  - Migratory intraocular cilium following phacoemulsification.
AB  - A case of an intraocular cilium noted in the anterior chamber after routine small
      incision phacoemulsification is described. The cilium was noted on the third
      postoperative day. It initially protruded internally from the paracentesis site
      and subsequently pierced the peripheral iris to migrate through to the posterior
      chamber to finally re-emerge through the pupil and come to rest in the inferior
      angle. No adverse effects have been noted and the patient's visual acuity was
      stable at 6/5 after 6 months of follow up.

PMID- 16451265
TI  - Anaesthetic abuse keratopathy as a manifestation of ocular Munchausen's syndrome.
AB  - Two patients, both with a history of major depressive disorder, presented with
      large bilateral corneal epithelial defects and ring-shaped stromal opacities.
      Both were initially treated unsuccessfully with topical antibiotic therapy for
      presumed infectious keratitis. One patient eventually admitted to topical
      anaesthetic abuse. In the second patient, signs of topical anaesthetic abuse and
      Munchausen's syndrome became evident. Cessation of anaesthetic use resulted in
      rapid resolution of the corneal epithelial defects in both patients. Anaesthetic
      abuse keratopathy is often a manifestation of underlying psychiatric illness, and
      psychiatric intervention is a very important part of management. To the authors'
      knowledge, this is the first report of ocular Munchausen's syndrome manifesting
      as anaesthetic abuse keratopathy.

PMID- 16451266
TI  - Congenital rubella cataract: a timely reminder in the new millennium?
AB  - Maternal infection with rubella in the first trimester is an important cause of
      congenital cataract. Any injury affecting the foetus following maternal rubella
      infection in the phase of organogenesis results in congenital defects
      collectively termed as congenital rubella syndrome (CRS). Although rubella
      embryopathy is a less common cause for congenital cataract than in the past, it
      is still seen. The number of cases reduced to one in 1997 after which there were
      no new cases till 2002. However, there have been two new cases of CRS in 2003.
      Herein another one in early 2004 is reported. Outbreaks of CRS will continue
      until the percentage of susceptible individuals is reduced to a minimum through
      immunization. The majority of rubella cases in Australia are confined to young
      female immigrants, many coming for marriage. We must continue to immunize
      children, identify and immunize vaccine failures and susceptible women before
      they become pregnant, and to screen pregnant women so they can be vaccinated
      after delivery.

PMID- 16451267
TI  - Ocular coherence tomography findings with retained submacular perfluoron.
AB  - Herein a case of retained perfluorocarbon liquid beneath the macula, following
      surgical repair of a complicated retinal detachment, is reported. The ocular
      coherence tomography findings were helpful in distinguishing retained
      perfluorocarbon liquid from residual subretinal fluid, macular cyst or cystoid
      macular oedema.

PMID- 16451268
TI  - Inadvertent sclerostomy with encysted bleb following trans-scleral contact diode
      laser cyclophotocoagulation.
AB  - A 22-year-old woman underwent 360 degrees trans-scleral contact diode laser
      cyclophotocoagulation for refractory glaucoma. Conjunctival burns and scleral
      thinning were noticed inferonasally at the last laser application. Intraocular
      pressure in the first week was normal. Six months later the patient presented
      with encysted filtering bleb and high intraocular pressure. Ultrasound
      biomicroscopy revealed a full thickness sclerostomy. This report suggests that
      inadvertent sclerostomy may present with encysted bleb months after trans-scleral
      contact diode laser cyclophotocoagulation.

PMID- 16451269
TI  - Traumatic optic nerve avulsion and central retinal artery occlusion following
      rugby injury.
AB  - Optic nerve avulsion (ONA) secondary to finger gouging is a rare complication. A
      case is reported of a 14-year-old boy who had an acute loss of vision after being
      poked in his left eye during a game of rugby union. He was later diagnosed with
      ONA, and this was associated with central retinal artery occlusion, which was
      rarely reported in the literature. His progress was complicated by a delayed
      onset of neovascular glaucoma. This is the first report of ONA secondary to a
      rugby injury and highlights the need for clinicians to be aware of the potential
      for loss of sight from gouging.

PMID- 16451270
TI  - Negative electroretinograms in pericentral pigmentary retinal degeneration.
AB  - The clinical presentation and electrophysiological findings are described of
      three consecutive cases with pericentral pigmentary retinal degeneration. The
      responses to bright flashes after dark adaptation showed negative waveform shape
      in all cases. Rod responses were strongly reduced compared with cone responses.
      Cone electroretinograms elicited by long-duration stimuli showed greater loss of
      the on-response than the off-response. The ratio of the on-response amplitude to
      off-response amplitude of these patients (0.52 +/- 0.12; mean +/- SD, n = 6) was
      significantly smaller than that of normal subject (0.83 +/- 0.21; mean +/- SD, n
      = 8) (Mann-Whitney U-test, P < 0.01). The electrophysiological findings of these
      cases suggest a greater defect of inner retinal function, especially in
      transmission between photoreceptors and depolarizing bipolar cells.

PMID- 16451273
TI  - Assessing the accuracy of Orbscan II post-LASIK: apparent keratectasia is
      paradoxically associated with anterior chamber depth reduction in successful
      procedures--comment.

PMID- 16451272
TI  - Glaucomatous optic neuropathy and the "baropathies".

PMID- 16451274
TI  - Nosology and the glaucomas.

PMID- 16451276
TI  - Indocyanine green-assisted macular pucker surgery.

PMID- 16451278
TI  - Pulse pressure and carotid atherosclerosis: an important link revisited?

PMID- 16451279
TI  - The second Princeton consensus on sexual dysfunction and cardiac risk: new
      guidelines, new challenges.

PMID- 16451280
TI  - Changes in organisation of oxygen therapy in England and Wales.

PMID- 16451281
TI  - Rasagiline -- is there a place for this drug in managing Parkinson's disease?

PMID- 16451283
TI  - Erectile dysfunction and statin treatment in high cardiovascular risk patients.
AB  - Erectile dysfunction (ED) has been associated with risk factors for
      atherosclerosis. Medications used for atherosclerosis have also been implicated
      in ED. The aim of this study is to investigate the relationship of erectile
      function to cardiovascular risk factors and specific drug therapies before and
      after 6 months of statin therapy. In this prospective observational study,
      International Index of Erectile Function (IIEF) scores were measured in 93 men
      attending cardiovascular risk clinics. Cardiovascular risk factors and drug
      therapies were assessed prior to initiation and after 6 months of statin therapy.
      Prior to statin therapy, the median IIEF score was 21 (range 0-25), and 57% had
      impairment of erectile function. After statin therapy, IIEF scores were reduced
      to 6.5 (range 0-25) (p < 0.001), and 22% experienced new onset ED. Before statin
      therapy no correlation was observed between IIEF score and any individual
      cardiovascular risk factor. After 6 months of statin therapy, correlations were
      observed between lower IIEF scores (r = 0.62; p < 0.001) and age and diabetes and
      weakly with smoking. Differences in dose, relative efficacy or relative
      lipophilicity of statin prescribed showed no correlation with change in IIEF
      score. This study suggests ED following statin therapy is more likely in patients
      with severe endothelial dysfunction due to established cardiovascular risk
      factors including age, smoking and diabetes.

PMID- 16451282
TI  - Pulse pressure, aortic regurgitation and carotid atherosclerosis: a comparison
      between hypertensives and normotensives.
AB  - Pulse pressure (PP) has often been associated with cardiovascular morbidity and
      mortality. Patients with aortic regurgitation (AR) often have increased PP. The
      aim of this study is to investigate the associations among PP, AR and
      extracranial carotid artery (ECCA) carotid atherosclerosis (CA) in hypertensives
      and age- and sex-matched normotensives. Two hundred and sixty-three hypertensive
      patients and 270 normotensive subjects from the Chin-Shan Community
      Cardiovascular Cohort participated in this study in 1996. CA, expressed as
      maximal common carotid artery intima-media thickness (IMT) > or = 75th percentile
      and ECCA plaque score > 6, was measured using high-resolution B-mode
      ultrasonography. The presence of AR was assessed by echocardiography, and their
      relationships with CA were evaluated. Results showed measurements of CA
      significantly associated with increased PP. Presence of AR associated with CA,
      but this relationship was attenuated after controlling for age. Multivariate
      logistic regression analyses revealed that an ECCA score > 6 significantly
      increase the risk in conjunction with PP, age and smoking in hypertensives.
      Correspondingly, CA increased with age, smoking and left ventricular hypertrophy
      on electrocardiography but not PP in normotensives. In conclusion, higher PP is
      strongly associated with CA in patients with hypertension. In terms of risk
      stratification, PP is more important in hypertensives than in normotensives which
      seem to imply that pulsatile haemodynamic component of BP is crucial in
      association with atherosclerosis.

PMID- 16451284
TI  - Do patients prescribed short-burst oxygen therapy meet criteria for ambulatory
      oxygen?
AB  - The aim of this study was to determine whether patients (n = 40) with chronic
      obstructive pulmonary disease (COPD) currently receiving short-burst oxygen
      therapy meet existing criteria for ambulatory oxygen. A prospective randomised
      balanced double-blind crossover design was used. Criterion (i) for ambulatory
      oxygen (desaturation by 4% to below 90% on the practice walk) was met in 21
      patients; 15 of these 21 patients also met criterion (ii) (10% improvement in
      distance and/or breathlessness score with oxygen). Despite no evidence of
      desaturation in 19/40 patients, 9/19 improved their distance and/or
      breathlessness score with oxygen. This study has shown that many patients on
      short-burst oxygen meet existing criteria for ambulatory oxygen and may have been
      receiving suboptimal therapy. It supports recent proposals for the development of
      comprehensive assessment services which incorporate assessment for all categories
      of oxygen.

PMID- 16451285
TI  - Validation of growth charts for girls with Turner syndrome.
AB  - Growth charts, which describe the natural course of growth in Turner syndrome
      (TS) patients, are commonly used in studies in lieu of control groups. While
      analysing data, various charts produce different final height estimations and
      height-gain predictions. The choice of an appropriate chart should be the first
      task when assessing effects of growth hormone treatment. The purpose of this
      study was to establish the most appropriate growth chart for the subsequent
      analysis of growth rate in the patients with TS observed initially for a short
      time without treatment in our clinic. We propose the criteria that a standardised
      chart should meet. The obtained height-standardised values (height standard
      deviation score -- Ht SDS) should represent normal distribution with a mean of 0
      and standard deviation of 1; their initial mean value and mean change in these
      values during observation without treatment should not be different from 0. We
      studied 62 untreated girls with TS using three different growth charts. The
      values of Ht SDS based on the Lyon chart showed a significant difference from
      normal distribution (p < 0.05). Only the mean value of an initiaent from 0 (p =
      0.088). The mean change of the Ht SDS value based on Lyon and Ranke charts during
      the follow-up period was not statistically different from 0 (p > 0.05), whereas
      the difference was statistically significant when the Wisniewski chart was used.
      Only the Ranke chart correctly characterised TS girls in our clinic. This
      analysis indicates the importance of careful selection of an appropriate growth
      chart for an observed population, before applying it to evaluate the effects of
      hormonal therapy.

PMID- 16451286
TI  - Hyperlipidaemia and outcome in acute pancreatitis.
AB  - There is a well-recognised association between hyperlipidaemia and acute
      pancreatitis. However, the role of hyperlipidaemia in modulating disease course
      is not clear. The aim of the study was to conduct a prospective study in acute
      pancreatitis to assess the relation between hyperlipidaemia and disease severity
      using current disease descriptors. The study population constituted 43 patients
      with acute pancreatitis, admitted during the calendar year 2001. There were 19
      (44%) males. The median (range) age was 50 (21-86) years. Serum triglycerides,
      cholesterol and high-density lipids were measured on admission. Patients were
      followed-up for at least 6 months after discharge. Principal outcomes were
      relation between hyperlipidaemia and peri-pancreatic complications and end-of
      episode disease severity. The results showed that hypertriglyceridaemia was
      present in 14 patients (33%). There was a significant difference in mean (SEM)
      serum triglyceride levels between patients with alcohol-induced pancreatitis
      compared with pancreatitis of other aetiologies [3.07 (1.0) mmol/l vs. 1.26
      (0.11) mmol/l; p = 0.03, Fisher's exact test]. There was no correlation between
      admission hypertriglyceridaemia and admission APACHE II score (r(2) = 0.0015).
      Similarly, there was no correlation between triglyceride level and either
      pancreatic inflammatory complications or final outcome. In conclusion, this study
      has demonstrated that there was no significant correlation between
      hypertriglyceridaemia and either complications of disease or overall end-of
      episode severity in this population of patients with acute pancreatitis.

PMID- 16451287
TI  - Prospective cohort study comparing sequential organ failure assessment and acute
      physiology, age, chronic health evaluation III scoring systems for hospital
      mortality prediction in critically ill cirrhotic patients.
AB  - The aim of the study was to evaluate the usefulness of sequential organ failure
      assessment (SOFA) and acute physiology, age, chronic health evaluation III
      (APACHE III) scoring systems obtained on the first day of intensive care unit
      (ICU) admission in predicting hospital mortality in critically ill cirrhotic
      patients. The study enrolled 102 cirrhotic patients consecutively admitted to ICU
      during a 1-year period. Twenty-five demographic, clinical and laboratory
      variables were analysed as predicators of survival. Information considered
      necessary to calculate the Child-Pugh, SOFA and APACHE III scores on the first
      day of ICU admission was also gathered. Overall hospital mortality was 68.6%.
      Multiple logistic regression analysis revealed that mean arterial pressure, SOFA
      and APACHE III scores were significantly related to prognosis. Goodness-of-fit
      was good for the SOFA and APACHE III models. Both predictive models displayed a
      similar degree of the best Youden index (0.68) and overall correctness (84%) of
      prediction. The SOFA and APACHE III models displayed good areas under the
      receiver-operating characteristic curve (0.917 +/- 0.028 and 0.912 +/- 0.029,
      respectively). Finally, a strong and significant positive correlation exists
      between SOFA and APACHE III scores for individual patients (r(2) = 0.628, p <
      0.001). This investigation confirms the grave prognosis for cirrhotic patients
      admitted to ICU. Both SOFA and APACHE III scores are excellent tools to predict
      the hospital mortality in critically ill cirrhotic patients. The overall
      predictive accuracy of SOFA and APACHE III is superior to that of Child-Pugh
      system. The role of these scoring systems in describing the dynamic aspects of
      clinical courses and allocating ICU resources needs to be clarified.

PMID- 16451288
TI  - Combined transurethral resection of prostate and inguinal mesh hernioplasty.
AB  - We aimed to evaluate the difference among early post-operative morbidities of
      transurethral resection of prostate (TURP), inguinal herniorrhaphy and their
      combination in this study. Between 1998 and 2004, 44 patients undergoing combined
      inguinal herniorrhaphy and TURP (Group I) were compared with 50 consecutive cases
      of TURP alone (Group II) and 50 consecutive cases of inguinal herniorrhaphy alone
      (Group III). There were no differences in the mean age and mean prostatic volume
      between Group I and II. The mean operation time and length of hospital stay were
      126.1 +/- 20.9 min, 3.0 +/- 0.7 days for Group I, 61.4 +/- 15.6 min and 2.9 +/-
      0.69 days for Group II and 55.0 +/- 15.6 min and 1.2 +/- 0.4 days for Group III,
      respectively. The mean operation time of Group I was found as longer than Group
      II and III. There were no significant differences among all groups regarding post
      operative complications. No mesh infection was detected. Combined TURP and
      inguinal herniorrhaphy is a practical, safe and effective procedure.

PMID- 16451289
TI  - Detection of virulence factors of Escherichia coli from children by multiplex
      polymerase chain reaction.
AB  - A total of 161 Escherichia coli (E. coli) strains isolated from children with
      urinary tract infection (UTI) were analysed for the genes encoding the virulence
      factors such as pyelonephritis (pap), s fimbriae (sfa), afimbrial adhesin I
      (afaI), haemolysin (hly), cytotoxic necrotising factor I (cnf I) and aerobactin
      (aer) by multiplex PCR. Ninety-four E. coli strains were found to carry at least
      one virulence factor. Therefore, 58.38% of total population was positive for one
      virulence gene at least. Percentage of genes within the total population for pap,
      sfa, afaI, hly, cnf I and aer was found as 22.98, 6.21, 9.94, 1.24, 9.94 and
      39.75, respectively. Our analysis showed that sfa-pap (p < 0.001); pap-aer, afaI
      aer and cnf I-pap (P < 0.05) and hly-sfa (p < 0.01) significantly co-occurred in
      their respective samples. In the light of these findings, we suggest an important
      role of pap causing UTI.

PMID- 16451290
TI  - Tuning fork (128 Hz) versus neurothesiometer: a comparison of methods of
      assessing vibration sensation in patients with diabetes mellitus.
AB  - The current study compared the effectiveness of the graduated tuning fork (128
      Hz) and the neurothesiometer in assessing vibration sensation perception in
      patients presenting with type II diabetes mellitus. A quota sample of patients (n
      = 21; age range 43-73 years) were assessed using the neurothesiometer and tuning
      fork by two investigators at five sites on both feet. There was a positive
      correlation between the results for the two methods of assessment for both
      investigators, and also between the results for both tools at three individual
      sites. Overall, there was 66.2% agreement between the results obtained from the
      two investigators using the tuning fork at each site; however, Kappa values only
      reached statistical significance at one site, indicating variability between the
      results from the two tools. This study suggests that assessment of vibration
      sensation with the tuning fork may be unreliable. These preliminary findings are
      based on a small sample size; thus further research is warranted.

PMID- 16451291
TI  - Angiotensin II-receptor blocker dosages: how high should we go?

PMID- 16451292
TI  - Managing stress urinary incontinence -- a primary care issue.
AB  - Stress urinary incontinence (SUI) is a common condition in women, caused by
      anatomical problems related to factors such as age, parity, menopause and
      obesity. Depending on the clinical findings and on the severity of symptoms, SUI
      can be managed with conservative methods including pelvic floor exercises,
      vaginal cones and general lifestyle modification advice; or, it can be treated
      surgically with procedures such as Burch colposuspension, vaginal slings or
      tension-free tapes and injection of bulking agents alongside the urethra. SUI is
      greatly underdiagnosed, because many women are reluctant to consult their doctors
      about their condition. Department of Health guidelines are placing greater
      emphasis on primary care management of the condition and Primary Care Trusts
      (PCTs) to provide consistent, integrated continence care services. The
      availability of new, non-invasive treatment options, such as duloxetine, are
      likely to have a positive impact on the future of SUI management.

PMID- 16451293
TI  - Management of acute bacterial rhinosinusitis: current issues and future
      perspectives.
AB  - Acute bacterial rhinosinusitis (ABRS), which manifests as an inflammation of at
      least one of the paranasal sinuses, is a major public health issue in developed
      countries. Diagnosis and treatment of ABRS can pose significant challenges in
      clinical practice, including difficulty in differentiation between viral and
      bacterial infection and a lack of simple, reliable and convenient methods for
      definitive diagnosis. Treatment choice is also a challenge because a decision is
      typically made empirically; therefore, the selection of therapy should be based
      on knowledge of local patterns of antimicrobial resistance, spectrum of activity
      against the most common ABRS pathogens (including those that are resistant to
      penicillins and macrolides) and pharmacodynamic potency. Current guidelines for
      diagnosis and treatment of ABRS in various countries share some similarities but
      also have important differences. Criteria for making the clinical diagnosis of
      sinusitis vary only slightly from country to country, while recommendations of
      therapy reflect the local impact of bacterial resistance.

PMID- 16451294
TI  - Interferon-induced sarcoidosis.
AB  - Interferons (IFNs) are widely used for the treatment of various medical diseases.
      They have marked immunomodulatory effects, and many reports have been published
      associating IFN therapy with the induction of autoimmune phenomena and other
      disorders of immune regulation such as sarcoidosis. The clinical presentation of
      IFN-induced sarcoidosis (IIS) is insidious and can be confused with common
      constitutional side effects of these drugs. The age of onset of IIS is later than
      that of naturally occurring sarcoidosis. The most common organs involved are the
      lungs and skin. In the majority of cases, IIS follows a benign course. As we show
      in an illustrative case report, complete resolution after discontinuation of IFN
      therapy can be expected. This review summarises 65 cases of IIS reported in the
      literature and highlights the pathophysiology, clinical features, diagnostic
      modalities and therapeutic options for this increasingly recognised phenomenon.

PMID- 16451295
TI  - Differential diagnosis between Crohn's disease and intestinal tuberculosis in
      China.
AB  - To evaluate the values of clinical findings in differential diagnosis between
      Crohn's disease (CD) and intestinal tuberculosis (ITb), so that better diagnosis
      strategies could be found, we analysed the records of 30 patients with ITb and 30
      patients with CD retrospectively. We reviewed the cardinal symptomatic and
      physical, radiological, colonoscopic, pathological findings in the patients. Some
      cardinal symptomatic and physical, radiographic and colonscopic features of CD
      and ITb were positive correlation. Its Pearson correlation coefficients were
      0.976, 0.953 and 0.961, respectively (p = 0.000, 0.003 and 0.000). Some
      histological features of CD and ITb had no correlation. Its Pearson correlation
      coefficient was 0.140 (p = 0.765). It is difficult to differentiate CD from ITb
      in clinical practice. The differential diagnosis depends largely upon colonoscopy
      and histopathology.

PMID- 16451296
TI  - Rasagiline: defining the role of a novel therapy in the treatment of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a therapy area with considerable unmet needs. The
      current key targets for PD treatment include the slowing of disease progression,
      improved control of motor fluctuations in advanced disease and the treatment of
      non-motor symptoms. In view of such major requirements, it is important to
      consider how new drug treatments fit into the context of PD therapy, and the
      practical advantages that they may offer in the management of PD in clinical
      practice. Rasagiline is a novel, second-generation, irreversible, selective
      monoamine oxidase type B inhibitor that is indicated for the treatment of
      idiopathic PD, either as initial monotherapy or as adjunct therapy (with
      levodopa) for patients experiencing end-of-dose motor fluctuations. This review
      assesses the outcome from several large-scale clinical studies that have
      investigated the use of rasagiline in early and advanced PD patient populations
      and discusses the role of rasagiline within the current scope of PD therapy.

PMID- 16451297
TI  - Ivabradine -- the first selective sinus node I(f) channel inhibitor in the
      treatment of stable angina.
AB  - Heart rate, a major determinant of angina in coronary disease, is also an
      important predictor of cardiovascular mortality. Lowering heart rate is therefore
      one of the most important therapeutic approaches in the treatment of stable
      angina pectoris. To date, beta-blockers and some calcium-channel antagonists
      reduce heart rate, but their use may be limited by adverse reactions or
      contraindications. Heart rate is determined by spontaneous electrical pacemaker
      activity in the sinoatrial node controlled by the I(f) current. Ivabradine is the
      first specific heart rate-lowering agent that has completed clinical development
      for stable angina pectoris. It is selective for the I(f) current, lowering heart
      rate at concentrations that do not affect other cardiac ionic currents. Specific
      heart-rate lowering with ivabradine reduces myocardial oxygen demand,
      simultaneously improving oxygen supply. Ivabradine has no negative inotropic or
      lusitropic effects, preserving ventricular contractility, and does not change any
      major electrophysiological parameters unrelated to heart rate. Randomised
      clinical studies in patients with stable angina show that ivabradine effectively
      reduces heart rate, improves exercise capacity and reduces the number of angina
      attacks. It has superior anti-anginal and anti-ischaemic activity to placebo and
      is non-inferior to atenolol and amlodipine. Ivabradine therefore offers a
      valuable approach to lowering heart rate exclusively and provides an attractive
      alternative to conventional treatment for a wide range of patients with confirmed
      stable angina.

PMID- 16451298
TI  - An unusual case of bowel perforation due to fish fin ingestion.
AB  - We reported the case of an 85-year-old woman who presented with an acutely tender
      abdomen and underwent abdominal computed tomography (CT) scanning initially
      reported as showing diverticulitis. After failed conservative management, this
      patient was taken to theatre, and laparotomy revealed a punctate perforation of
      the ileum due to a 4 x 3 cm fish fin, which was removed through enterotomy.
      Retrospective analysis of the initial CT scans showed a foreign body consistent
      with that removed. This is the first case documented in the literature of
      perforation of bowel due to fish fin ingestion, as opposed to fish bone. It
      highlights firstly how common presentations may have an uncommon cause and
      secondly, how easily a small foreign body can be missed on CT scan. It also
      highlights and the importance of (i) eliciting a full history of eating habits in
      those presenting with abdominal pain and (ii) basing intervention on clinical
      findings. In this case report, we review the wider medical literature on
      perforation due to foreign body ingestion.

PMID- 16451299
TI  - What we see is not what we get in catamenial haemoptysis.
AB  - Catamenial haemoptysis is rare entity, a part of thoracic endometriosis syndrome.
      We present a young woman who was timely diagnosed, successfully treated using
      video-assisted thoracoscopic surgery and pathologically confirmed the case. The
      change in lung parenchyma over time in the computed tomography is highlighted.

PMID- 16451300
TI  - Press through package mis-swallowing.
AB  - A press through package (PTP) is commonly used as a package for drugs and also
      being seen increasingly in cases of foreign body in the digestive tract. We
      presented three cases of inadvertent PTP ingestion with a variety of clinical
      presentations. Although commonly considered to be small and soft to cause bowel
      damage, a PTP tends to be caught and poses potential risk for perforation of the
      bowel because of its sharp edges. The PTP material is thought to be difficult to
      detect on plain abdominal roentgenography due to its radiolucency. However, air
      trapped in the PTP makes the drug tablet possibly visible on the radiograph. All
      of the three cases were diagnosed with correct interpretation of these special
      radiographic findings, even without the recall of accidental swallowing of the
      tablet. A PTP in the oesophagus and stomach should be tried to be removed, while
      computerised tomography and early laparotomy should be considered when it passes
      through the pyloric ring and the patient develops symptoms. An effort to prevent
      the PTP swallowing should be an essential part in our everyday practice,
      especially for the elderly patients.

PMID- 16451301
TI  - Guiding Principles for Pharmaceutical Physicians from the Ethical Issues
      Committee of the Faculty of Pharmaceutical Medicine of the Royal Colleges of
      Physicians of the UK.
AB  - Medical practitioners practising in the field of pharmaceutical medicine, whether
      in industry, regulatory bodies or an academic environment, are bound by the same
      ethical standards which apply to all doctors. Their work, however, leads to some
      very specific ethical considerations which may not be fully explored in ethical
      codes based in clinical medicine. This document aims to establish some guiding
      principles which should underpin a working ethical framework for pharmaceutical
      physicians. It clearly places the protection of patients (and research subjects)
      and the doctor's duties to wider society ahead of responsibilities to an
      individual employer while emphasising the importance of adherence to high
      standards of research, including dissemination of findings. These principles form
      the basis of a fuller report which offers more specific practical advice on
      possible ethical conflicts or dilemmas.

PMID- 16451302
TI  - Ethics and pharmaceutical medicine -- the full report of the Ethical Issues
      Committee of the Faculty of Pharmaceutical Medicine of the Royal Colleges of
      Physicians of the UK.
AB  - The practice of pharmaceutical medicine brings with it ethical challenges and
      dilemmas often very different from those encountered in the practice of clinical
      medicine. Having established a framework of guiding ethical principles, this
      report aims to look in some detail at specific areas of possible ethical concern
      to pharmaceutical physicians, offering practical advice and guidance on good
      practice. The report covers issues related to pharmaceutical research, including
      dissemination of research findings, communication with other health professionals
      and patients and involvement of pharmaceutical physicians and companies in the
      provision of patient services. The primacy of the interests of patients and the
      wider public is emphasised, and the possible impact of new developments in
      pharmaceutical technology is explored. It is hoped that the report will help
      those working in pharmaceutical medicine and act as a stimulus for wider
      discussion and debate.

PMID- 16451303
TI  - Evidence for prescribing exercise as therapy in chronic disease.
AB  - Considerable knowledge has accumulated in recent decades concerning the
      significance of physical activity in the treatment of a number of diseases,
      including diseases that do not primarily manifest as disorders of the locomotive
      apparatus. In this review we present the evidence for prescribing exercise
      therapy in the treatment of metabolic syndrome-related disorders (insulin
      resistance, type 2 diabetes, dyslipidemia, hypertension, obesity), heart and
      pulmonary diseases (chronic obstructive pulmonary disease, coronary heart
      disease, chronic heart failure, intermittent claudication), muscle, bone and
      joint diseases (osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia,
      chronic fatigue syndrome) and cancer, depression, asthma and type 1 diabetes. For
      each disease, we review the effect of exercise therapy on disease pathogenesis,
      on symptoms specific to the diagnosis, on physical fitness or strength and on
      quality of life. The possible mechanisms of action are briefly examined and the
      principles for prescribing exercise therapy are discussed, focusing on the type
      and amount of exercise and possible contraindications.

PMID- 16451305
TI  - Randomized controlled clinical trials on agents used for chemical plaque control.
AB  - Taking into account the limitations of the daily self-performed oral hygiene the
      use of chemical agents that can be incorporated in dentifrice or mouth rinse
      formulations has been advocated. The present review deals with randomized
      controlled clinical trials of >or=6 months in duration, on the use of those
      agents and their effects on plaque and gingival inflammation.

PMID- 16451306
TI  - Dysphagia management in a 3-year dental hygiene education programme in Japan.
AB  - This paper reports the development and evaluation of a dysphagia management
      course taught to the third year dental hygiene students during 2004-2005 as one
      framework of the new curriculum. The course consisted of lectures by specialists
      in each field, basic practice and clinical practice at a facility for the
      elderly. Evaluation of the course showed that improvements were found in
      students' understanding in certain subjects when compared with that during 2003
      2004. Scores on the post-test were statistically significantly higher than those
      on the pre-test, showing that basic knowledge of the students had been improved.
      Introductory and follow-up lectures by dental hygiene instructors and appropriate
      basic practice enhanced the learning process of the students. In the clinical
      practice, the concept of 'dental hygiene process of care' was incorporated. The
      dental hygiene process facilitated the students in planning and implementing
      dental hygiene care that meets the needs of the individual clients. This active
      learning experience enhanced the students' understanding of dysphagia management.
      Although further improvements are necessary, this dysphagia management course
      should help dental hygienists in playing a greater role in the field of oral care
      and dysphagia rehabilitation.

PMID- 16451307
TI  - A proposed model for a collaborative approach to dental hygiene research.
AB  - As dental hygiene responds to the increased need for quality oral health
      services, dental hygienists seek quality research findings on which to base their
      practice decisions. However, the amount of research published by dental
      hygienists, and addressing dental hygiene interventions, remains limited. There
      are few dental hygienists in Canada working in positions that have time dedicated
      to research activities. To increase the amount of dental hygiene research,
      innovative approaches such as collaborative research must be considered. This
      paper considers measures that facilitate the conduct of collaborative research,
      and discusses challenges to the process that should be considered during the
      design. An example of a group investigation is presented, involving dental
      hygiene educators who collaborated on a research project implemented within their
      respective educational institutions. A model for a collaborative approach to
      future research initiatives is proposed. Lessons learned are shared and
      recommendations are put forward. It is suggested that innovative collaborations
      such as this may help to increase the body of knowledge for dental hygiene in
      Canada.

PMID- 16451309
TI  - Dental hygienists on top of the world: supporting oral health education in Nepal.
AB  - This article describes the oral health situation in Nepal. Based on research and
      strategic planning reports from the WHO and the Ministry of Health in Nepal the
      value of Oral Health Promotion in Nepal is being promoted. The implications of
      possible dental treatment and/or oral health promotions are being discussed. A
      plan for support of improvement of the oral health in Nepal is presented. The
      main focus is the support of the development of the dental hygiene education and
      profession in Nepal. Another focus of attention is the ability of dental
      hygienists in Nepal to develop them individually and to create independent
      professionalization. This article forms the basis for developing a 5-year
      collaborative programme with Kantipur School of Dentistry and the Dental Hygiene
      Education, Amsterdam. It can be a means to inspire dental hygienists around the
      world to put efforts into improving oral health in developing countries.

PMID- 16451308
TI  - The effectiveness of self-performed mechanical plaque control with triclosan
      containing dentifrices.
AB  - OBJECTIVE: To assess the effectiveness of self-performed mechanical plaque
      control with triclosan (5-chloro-2-(2,4 dichlorophenoxy)phenol) containing
      dentifrice. SEARCH STRATEGY: An electronic search of the National Library of
      Medicine, Washington DC (Medline-PubMed; up to and including March 2005) was
      performed using specific search terms to identify clinical trials of >or=6 months
      in duration, which assessed the effect of various forms of plaque control in
      gingivitis subjects. In those trials the manual toothbrush group (frequently the
      control group) served to provide data for the assessment of the effectiveness of
      self-performed mechanical plaque control with a triclosan-containing dentifrice.
      The data were analysed depending on the (baseline) intervention, being either a
      professional oral hygiene instructions, a prophylaxis, or both. DATA COLLECTION
      AND ANALYSIS: Two reviewers extracted information (KPKJH and GAW). Where
      appropriate plaque and gingivitis data for baseline and end-trial were used to
      calculate weighted mean differences (WMD) with the appropriate 95% confidence
      intervals (CI) using a random effect models. MAIN RESULTS: Of 105 titles and
      abstracts, 18 trials were found suitable for clinical data were extracted. Meta
      analysis were conducted. In studies (n=9) evaluating a triclosan/copolymer
      dentifrice, plaque control [Quigley and Hein (1962) Journal of American Dental
      Association, Vol. 65: pp. 26-29] was significantly improved compared with a
      control fluoride dentifrice, with a WMD of -0.48 (95% CI: -0.73 to -0.24). For
      gingival inflammation as assessed with the gingival index [Loe and Silness (1963)
      Acta Odontologica Scandinavica, Vol. 21: pp. 533-551] a significant WMD of -0.24
      (95% CI: -0.35 to -0.13) was found. From studies (n=6) evaluating the Triclosan
      zinc/citrate dentifrices a small but significant WMD for plaque control [Silness
      and Loe (1964) Acta Odontologica Scandinavica, Vol. 22: pp. 121-135] was observed
      in favour of the test group as compared with the standard fluoride dentifrice
      formulations (WMD -0.07, 95% CI: -0.10 to 0.05). While at baseline the proportion
      of bleeding was comparable, at the end of the studies a significant -10.81% WMD
      (95% CI: -12.69 to -8.93) in favour of the triclosan/zinc citrate dentifrice was
      observed. CONCLUSION: This systematic review indicates, based on studies >or=6
      months of duration in adults with gingivitis, that the effectiveness of self
      performed mechanical plaque control with a triclosan-containing dentifrice, had a
      significant albeit small positive effect on the reduction of plaque and
      gingivitis.

PMID- 16451310
TI  - Oral Hygiene and dental student's knowledge, attitude and behaviour in managing
      HIV/AIDS patients.
AB  - The human immunodeficiency virus (AIDS) and the acquired immunodeficiency
      syndrome (AIDS) have profoundly affected every aspect of the public health
      sector. The possibility of HIV transmission in the oral health care setting is
      very rare. Nonetheless, the oral health care environment has become a helpful
      setting for early detection, as most lesions of HIV infection present orally
      during the first stages of the disease. Willingness to treat patients with
      HIV/AIDS appears to be related to knowledge of the disease process, its oral
      manifestations and modes of transmission, thus influencing health workers'
      attitudes and behaviour towards management of HIV/AIDS patients. This study
      assessed the level of management of HIV/AIDS patients amongst dental and oral
      hygiene students at the University of the Western Cape Dental faculty. Student's
      knowledge of HIV/AIDS, their behaviour and attitude in treating HIV/AIDS
      patients, the precautionary measures practiced and their perceptions of
      curriculum preparation on HIV/AIDS were assessed. Data were collected by means of
      a self- administered questionnaire. The results indicated that students'
      knowledge on HIV/AIDS generally increased as they progressed throughout their
      curriculum but their utilization of all barrier techniques for infection control
      and clinical protocol, lacked consistency and compliance. Given the fact that the
      possibility of transmission of HIV/AIDS does exist within the dental setting, it
      is important that supervisors reinforce universal precautions. Clinical
      application of these precautions has a direct impact on the spread of the
      disease.

PMID- 16451311
TI  - Treatment planning.

PMID- 16451312
TI  - American heart association.

PMID- 16451313
TI  - Is your knowledge up-to-date?

PMID- 16451315
TI  - Towards the feeling of emergence.
AB  - Emergence is a multi-dimensional notion; the meanings it has acquired span the
      mythopoetic to the scientific, especially as found in complex systems. Examples
      of emergence in Navaho and Egyptian imagery underscore its diverse cultural
      origins and applications as well as suggesting an underlying archetypal quality
      to the core concept. A brief overview of the use of this term in science starting
      in the 17th century helps to locate the roots of modern emergent views in the
      philosophy of Leibniz. Jung's own use of early systems approaches was a part of
      his formulations of a 'third' position associated with the transcendent function.
      As this paper was delivered at the 50th anniversary conference of the Journal of
      Analytical Psychology, aspects of the emergence of the Journal within the
      contents of the first issue are explored. Attention is drawn to several articles,
      especially a case of brief child therapy done by Robert Moody. His approach to
      working his case is strikingly modern and vividly demonstrates principles of
      emergence within the clinical setting. Following this there is a discussion of
      some neuroscientific research on neural body maps, pointing to the experience of
      feelings as an emergent process. It is suggested that feelings derive from phase
      transitions in the brain's body mapping states. A reconsideration of a seeming
      impasse in the case described by Moody leads instead to a view of the initial
      phase of treatment as a pre-critical period. Research findings on mirror neurons
      are presented in terms of the feeling of empathy. Subjective feelings are then
      shown to be associated with moments of emergence, especially surprise and
      curiosity, exemplified by a case from the author's practice.

PMID- 16451316
TI  - Imagination and the imaginary.
AB  - This paper argues that real imagination depends on the capacity to acknowledge
      the absence of what is imagined from the world of material actuality. This leads
      on to a view of symbol formation as the operation of the transcendent function
      between the opposites of presence and absence. 'The imaginary' is contrasted with
      this as a defensive misuse of imagination that attempts to deny 'negation' where
      negation is defined as all those aspects of the world that constitute a check to
      the omnipotence of fantasy--e.g., absence, loss, difference, otherness etc.
      Parallels are drawn with theoretical antecedents in analytical psychology and
      psychoanalysis, with particular attention to papers published in the Journal of
      Analytical Psychology (JAP) in the 1960s on the relation between active
      imagination, transference and ego development. A clinical example is given to
      show the use of the imaginary as a means of warding off the unbearable pain of
      Oedipal disappointment.

PMID- 16451317
TI  - The dreaming mind-brain: a Jungian perspective.
AB  - In this paper I discuss the nature and role of dream and the dreaming process in
      Jungian clinical practice in the light of neuroscience. Insights from
      contemporary neuroscience support rather than contest Jung's view that emotional
      truth, not censorship or disguise, underpins the dreaming process. I use clinical
      material to illustrate how work with dreams within the total interactive
      experience of the analytic dyad enables the development of the emotional
      scaffolding necessary for the development of 'mind'. Large scale evidence-based
      research reveals that dreaming is caused by brain activity during sleep that is
      both biochemically and regionally different from that of waking states. Recent
      imaging studies confirm that dreams are the mind's vehicle for the processing of
      emotional states of being, particularly the fear, anxiety, anger or elation that
      often figure prominently. Dream sleep is understood as also being the guardian of
      memory, playing a part in forgetting, encoding and affective organization of
      memory. In the clinical section of the paper I let a series of dreams speak for
      themselves, revealing the emotionally salient concerns of the dreamer, weaving
      past and present, transference and reality together in a way that demonstrates
      the healthy attempt of the brain-mind to come to terms with difficult emotional
      experience from the past. The dreams become dreamable as part of the meaning
      making process of analysis.

PMID- 16451318
TI  - Response to Margaret Wilkinson.

PMID- 16451319
TI  - A Spinozan lens onto the confusions of borderline relations.
AB  - In this paper the author describes how, in his analytic work with difficult
      personality disorders, he uses a neo-Spinozan position or attitude of alpha
      thinking and functioning to understand, clarify, and so to manage confused and
      confusing psychosomatic 'body-mind' and emotional relations, both internally and
      inter-personally. Two case examples are given, followed by reflections on
      technique and on the limits of mourning, transformation and irony. The author
      suggests that a private, ideational double-aspect, mind-body position may be
      helpful in working with these analysands. This analytic mode may create a
      radically different understanding by incorporating a relational system of
      containment, self-containment, observation and memory. In addition, the author
      gives his own version of the aetiology and dynamics of borderline states and
      relations, and weaves the two cases he reports on into reflections on his
      countertransferential responses, reactions, inter-actions and 'reverie' through
      the lens of a neo-Spinozan conceptual system.

PMID- 16451320
TI  - The interdisciplinary approach to Jungian clinical practice in the IAAP and the
      JAP.

PMID- 16451322
TI  - The IAAP and the JAP: a brief history of their management of theoretical
      diversity.

PMID- 16451323
TI  - The complementary roles of the IAAP and the JAP in developing Jungian clinical
      practice.

PMID- 16451324
TI  - The analyst's body as tuning fork: embodied resonance in countertransference.
AB  - This paper examines the phenomenon of embodied countertransference: where the
      analyst experiences a somatic reaction rather than the more common
      countertransference responses of thoughts, feelings, images, fantasies and
      dreams. Discussion of clinical material considers neurotic and syntonic aspects.
      The analogy is made of resonance with a tuning fork. Several questions are posed:
      Why does countertransference resonate in the bodies of some analysts but not all?
      Why do those analysts who are sensitive to this, experience it with some patients
      but not with others? And what are the conditions which are conducive to producing
      somatic responses? It proposes that somatic reactions are more likely to occur
      when a number of conditions come together: when working with patients exhibiting
      borderline, psychotic or severe narcissistic elements; where there has been early
      severe childhood trauma; and where there is fear of expressing strong emotions
      directly. In addition another theoretical factor is proposed, namely the typology
      of the analyst.

PMID- 16451325
TI  - The developmental/emergent model of archetype, its implications and its
      application to shamanism.
AB  - This paper addresses the ongoing debate in the JAP to do with archetype theory
      and supports an emergent/developmental model which sees archetypal imagery as an
      emergent phenomenon arising out of neural bio-structures laid down in early
      infant life as a result of developmental experience. This model is supported by
      the current findings of those developmental biologists who adhere to
      Developmental Systems Theory. The themes of Developmental Systems Theory are
      examined and corroborative parallels are drawn with the model. A number of
      implications follows: the model has substantial explanatory power and leads to a
      new perspective on innatism; it implies an archetype-environment nexus; it
      collapses the nature-nurture debate in relation to archetype theory; it collapses
      the 'sacred heritage' approach to archetypes and it removes the conceptual
      division between the collective and personal unconscious. This
      developmental/emergent perspective is then applied to the shaman archetype, using
      ethnographic records of the Sakha (Yakut) Siberian tribe. The material supports
      the hypothesis that the shamanic complex is laid down in early infancy by a
      combination of events which cause emotional ruptures in the mother-infant dyad.
      Siberian shamanism is then understood to arise out of developmental experience
      and not from the constellation of an autochthonous archetype.

PMID- 16451326
TI  - Endnotes: clinical developments and organizational containment.

PMID- 16451335
TI  - Editorial: Global elimination of lymphatic filariasis: fact or fantasy?
AB  - In 1997, the World Health Assembly resolved to eliminate lymphatic filariasis as
      a public health problem by the year 2020. By the end of 2004, almost half of the
      83 endemic countries had initiated national programmes, providing mass drug
      administration to an at risk population of approximately 435 million. This
      remarkable achievement is the result of an enormous amount of technical,
      financial and political support from public and private sectors at the community,
      national, regional and global level. As the global programme to eliminate
      lymphatic filariasis enters its second quarter of operations, there are
      substantial opportunities to be taken and critical challenges to be addressed.
      These are the focus of this editorial.

PMID- 16451336
TI  - Short communication: Negative spatial association between lymphatic filariasis
      and malaria in West Africa.
AB  - OBJECTIVE: To determine the relationship between human lymphatic filariasis,
      caused by Wuchereria bancrofti, and falciparum malaria, which are co-endemic
      throughout West Africa. METHODS: We used geographical information systems and
      spatial statistics to examine the prevalence of lymphatic filariasis in relation
      to malaria prevalence, mosquito species distributions, vegetation and climate.
      RESULTS: A negative spatial association between W. bancrofti and falciparum
      malaria prevalence exists. Interspecies competition between parasites,
      seasonality, differences in the distribution and vector competence of Anopheles
      vectors, agricultural practices and insecticide resistance may be factors driving
      current (and potentially future) spatial distributions. CONCLUSION: Further
      investigating these factors will become crucial as large-scale lymphatic
      filariasis and malaria control programmes are implemented in West Africa that may
      influence the epidemiology of both diseases.

PMID- 16451337
TI  - [The impact of war on the evolution of sleeping sickness in west-central Cote
      d'Ivoire].
AB  - OBJECTIVE: To evaluate the situation of sleeping sickness in west-central Cote
      d'Ivoire from 2000 to 2003, in view of the war which broke out in September 2002.
      METHODS: Active surveys by medical teams and passive case detection. RESULTS:
      Between 2000 and 2003, 250 patients were diagnosed with sleeping sickness. At
      first it appeared that sleeping sickness prevalence had fallen since the
      beginning of political troubles. But this apparent drop was due to poor
      population coverage. Participation in medical surveys differed according to
      ethnic group, reflecting land use conflicts between ethnic communities. Such
      conflicts are common in this area, but have been exacerbated by the war.
      CONCLUSION: In war, assessing the importance of sleeping sickness by medical
      surveys only is very difficult. But detection of sleeping sickness cases by
      passive surveillance increased.

PMID- 16451338
TI  - Drug-resistance of Trypanosoma b. rhodesiense isolates from Tanzania.
AB  - OBJECTIVE: To determine the drug resistance of Trypanosoma brucei rhodesiense
      strains isolated from sleeping sickness patients in Tanzania. METHOD: We first
      screened 35 T. b. rhodesiense strains in the mouse model, for sensitivity to
      melarsoprol (1.8, 3.6 and 7.2 mg/kg), diminazene aceturate (3.5, 7 and 14 mg/kg),
      suramin (5, 10 and 20 mg/kg) and isometamidium (0.1, 1.0 and 2 mg/kg). A 13
      isolates suspected to be resistant were selected for further testing in vitro and
      in vivo. From the in vitro testing, IC(50) values were determined by short-term
      viability assay, and MIC values were calculated by long-term viability assay. For
      in vivo testing, doses higher than those in the initial screening test were used.
      RESULTS: Two T. b rhodesiense stocks expressed resistance in vivo to melarsoprol
      at 5 mg/kg and at 10 mg/kg. These strains had high IC(50) and MIC values
      consistent with those of the melarsoprol-resistant reference strain. Another
      isolate relapsed after treatment with 5 mg/kg of melarsoprol although it did not
      appear resistant in vitro. One isolate was resistant to diminazene at 14 mg/kg
      and another was resistant at both 14 and 28 mg/kg of diminazene. These two
      isolates had high IC(50) values consistent with the diminazene-resistant
      reference strain. Two isolates relapsed at a dose of 5 mg/kg of suramin, although
      no isolate appeared resistant in the in vitro tests. Two isolates were resistant
      to isometamidium at 1.0 mg/kg and had higher IC(50) values. Two isolates were
      cross-resistant to melarsoprol and diminazene and one isolate was cross-resistant
      to suramin and isometamidium. CONCLUSION: The reduced susceptibility of T. b.
      rhodesiense isolates to these drugs strongly indicates that drug resistance may
      be emerging in north-western Tanzania.

PMID- 16451340
TI  - Accessibility of diagnostic and treatment centres for visceral leishmaniasis in
      Gedaref State, northern Sudan.
AB  - OBJECTIVE: To evaluate the accessibility of visceral leishmaniasis (VL)
      treatment. METHOD: Community-based study using in-depth qualitative interviews
      and focus group discussions with key informants, as well as quantitative
      questionnaires with 448 randomly selected heads of households in nine
      representative villages in three geographical sub-regions. RESULTS: Despite the
      high incidence of the disease, most people in Gedaref State know little about VL,
      and help at a treatment centre is usually sought only after traditional remedies
      and basic allopathic drugs have failed. Factors barring access to treatment are:
      lack of money for treatment and transport, impassability of roads, work
      priorities, severe cultural restrictions of women's decision-making power and
      distance to the next health center. CONCLUSIONS: To provide more VL patients with
      access to treatment in this highly endemic area, diagnostic and treatment
      services should be decentralized. Health education would be a useful tool to
      rationalise people's health-seeking behaviour.

PMID- 16451339
TI  - Clinical value of anti-live Leishmania (Viannia) braziliensis immunoglobulin G
      subclasses, detected by flow cytometry, for diagnosing active localized cutaneous
      leishmaniasis.
AB  - OBJECTIVE: To evaluate the clinical value of flow cytometry anti-live
      promastigate antibody (FC-ALPA), for diagnosing active cutaneous leishmaniasis.
      METHOD: Serum samples from 145 individuals living in endemic areas for localized
      cutaneous leishmaniasis (population 1) were classified as having the disease or
      not and then tested for their IgG reactivity by indirect immunofluorescence assay
      and FC-ALPA-IgG. The results of FC-ALPA-IgG were expressed as percentage of
      positive fluorescent parasite. Both tests were also evaluated in serum samples of
      people with visceral leishmaniasis and Chagas disease (population 1A). RESULTS:
      In population 1, FC-ALPA-IgG performed better than the immunofluorescence assay
      regarding sensitivity, specificity and predictive values. Analysis of the results
      according to the likelihood ratios indicated that a percentage of positive
      fluorescent parasite <or=60 practically excludes the diagnosis of localized
      cutaneous leishmaniasis (likelihood ratio=0.07), whereas at >60% it reinforces
      diagnosis of the disease (likelihood ratio = 7.0). Immunofluorescent assay is of
      little value (likelihood ratio=2.04). In population 1A, both tests performed
      worse, but FC-ALPA-IgG achieved better statistical indexes than immunofluorescent
      assay. CONCLUSION: The FC-ALPA-IgG is a valuable method for serological diagnosis
      of localized cutaneous leishmaniasis. FC-ALPA-IgG1/ALPA-IgG2 combined analysis is
      an additional serological tool for discriminating localized visceral
      leishmaniasis, Chagas disease and visceral leishmaniasis in areas where these
      infections co-exist.

PMID- 16451341
TI  - Condom use after voluntary counselling and testing in central Mozambique.
AB  - OBJECTIVE: To evaluate the efficacy of voluntary counselling and testing (VCT)
      for HIV/AIDS in changing risky sexual behaviour in central Mozambique. METHOD:
      Longitudinal cohort study of men and women aged at least 18 years from October
      2002 to June 2003. We interviewed 622 participants in VCT groups and 598 in non
      VCT groups. The interviews occurred before counselling and 4 and 6 months
      afterwards. RESULTS: Reported use of condoms while having sex with a
      friends/prostitute increased over each time period in the VCT group and between
      baseline and first visit in the non-VCT group. Both men and women in the VCT
      group increased their condom use over time, but the women in the non-VCT group
      did not. Reported always/sometimes use of condoms for both literate and
      illiterate subjects was higher and rose over time in the VCT group. CONCLUSION:
      People who undergo voluntary counselling and testing fro HIV/AIDS change their
      behaviour, presumably as a result of their counselling.

PMID- 16451342
TI  - Differences in fertility by HIV serostatus and adjusted HIV prevalence data from
      an antenatal clinic in northern Uganda.
AB  - OBJECTIVES: To estimate differences in fertility by HIV serostatus and to
      validate an adjustment method for estimating the HIV prevalence in the general
      female population using data from an antenatal clinic. METHODS: We used Cox
      regression models to retrospectively estimate the age-specific relative fertility
      (RF) of HIV-positive compared to HIV-negative women among 3314 antenatal clinic
      attenders in northern Uganda. RF and the age distribution of women in the general
      female population were used to extrapolate the antenatal clinic-based HIV
      prevalence. This procedure was indirectly validated by comparing the adjusted
      estimate with those based on standard adjustment factors derived from general
      female populations in Uganda and Tanzania. RESULTS: HIV-positive women reported a
      lower fertility than HIV-negative women [age-adjusted RF=0.83, 95% confidence
      interval (CI): 0.75-0.93]. Except for girls aged 15-19 (RF=0.96, 95% CI: 0.74
      1.24) HIV-positive women in all age groups were less fertile (20-24 year:
      RF=0.83, 95% CI: 0.67-1.01; 25-29 years: RF=0.79, 95% CI: 0.62-1.00; 30-49 year:
      RF=0.79, 95% CI: 0.65-0.96]. Adjusting the antenatal clinic-based HIV prevalence
      (11.6%) for these differences yields a higher estimate (13.8%) that is lower than
      those based on standard adjustment factors derived from general female
      populations (from 14.6% to 17.7%). CONCLUSIONS: The age-specific pattern of
      differential fertility by HIV serostatus derived from antenatal clinic data is
      consistent with findings from population-based studies conducted in Africa.
      However, differences in fertility between HIV positive and HIV-negative clients
      underestimate those in the general female population yielding inaccurate
      estimates when used to extrapolate the HIV prevalence.

PMID- 16451343
TI  - Modelling distances travelled to government health services in Kenya.
AB  - OBJECTIVE: To systematically evaluate descriptive measures of spatial access to
      medical treatment, as part of the millennium development goals to reduce the
      burden of HIV/AIDS, tuberculosis and malaria. METHODS: We obtained high
      resolution spatial and epidemiological data on health services, population,
      transport network, topography, land cover and paediatric fever treatment in four
      Kenyan districts to develop access and use models for government health services
      in Kenya. Community survey data were used to model use of government health
      services by febrile children. A model based on the transport network was then
      implemented and adjusted for actual use patterns. We compared the predictive
      accuracy of this refined model to that of Euclidean distance metrics. RESULTS
      Higher-order facilities were more attractive to patients (54%, 58% and 60% in
      three scenarios) than lower-order ones. The transport network model, adjusted for
      competition between facilities, was most accurate and selected as the best-fit
      model. It estimated that 63% of the population of the study districts were within
      the 1 h national access benchmark, against 82% estimated by the Euclidean model.
      CONCLUSIONS: Extrapolating the results from the best-fit model in study districts
      to the national level shows that approximately six million people are currently
      incorrectly estimated to have access to government health services within 1 h.
      Simple Euclidean distance assumptions, which underpin needs assessments and
      against which millennium development goals are evaluated, thus require
      reconsideration.

PMID- 16451344
TI  - Isolation of a Plasmodium vivax refractory Anopheles culicifacies strain from
      India.
AB  - Anopheles culicifaciessensu lato comprises five sibling species. We report the
      isolation of an An. culicifacies species B strain which is completely refractory
      to Plasmodium vivax sporogonic development and partially refractory to P.
      falciparum. Parasite development in this strain is arrested by a melanotic
      encapsulation mechanism in the mid-gut. We compare the infectivity of this
      refractory strain and four other species B strains from different epidemiological
      zones of India with P. vivax in the laboratory.

PMID- 16451345
TI  - Urban malaria in the Sahel: prevalence and seasonality of presumptive malaria and
      parasitaemia at primary care level in Chad.
AB  - OBJECTIVE: To assess malaria prevalence rates and seasonal patterns among
      clinically diagnosed malaria cases at the level of primary care facilities in an
      urban Sahelian setting. METHOD: Screening all patients consulting two private and
      two governmental providers on a randomly selected weekday over a period of 9
      months. Patients with presumptive malaria underwent a blood test. RESULTS: Of
      1658 patients included in the survey, 47% were clinically diagnosed and treated
      as malaria cases. Malaria was more often diagnosed by private providers. There
      were no clear seasonal patterns in presumptive malaria. A 30% of clinically
      diagnosed cases were positive for Plasmodium (all falciparum) by thick film
      examination. Thus, false positive cases constituted more than 70% of the
      clinically diagnosed malaria cases. The highest positive prevalence rates were
      found at the end and shortly after the rainy season (44%-47%) and the lowest
      during the dry season (2%). CONCLUSIONS: Clinical diagnosis of malaria has a very
      low positive predicted value in this low endemicity urban setting, and its low
      specificity leads to inappropriate care for a large proportion of patients. This
      has a major impact on economic costs for health services and households. In the
      Sahel, systematic use of microscopy-based diagnosis and/or rapid diagnostic tests
      should be considered to appropriately manage malaria and non-malaria cases.

PMID- 16451346
TI  - In vivo sensitivity monitoring of mefloquine monotherapy and artesunate
      mefloquine combinations for the treatment of uncomplicated falciparum malaria in
      Thailand in 2003.
AB  - OBJECTIVE: To monitor the efficacy of anti-malarial treatments in Thailand.
      METHOD: A 28-day in vivo study in nine provinces along international borders in
      2003. The first group comprised 164 patients from four provinces: Mae Hong Son,
      Chiang Mai, Ratchaburi and Ubon Ratchathani. These patients received 15 mg/kg
      mefloquine as a single dose. The second group, 58 patients from Kanchanaburi,
      were treated with 15 mg/kg mefloquine plus artesunate (12 mg/kg). The third
      group, 196 patients from provinces with high-level mefloquine resistance (Tak,
      Ranong, Chanthaburi and Trat), received 25 mg/kg of mefloquine plus 12 mg/kg
      artesunate. In all arms, follow-up blood smears were scheduled for days 1, 2, 3,
      7, 14, 21 and 28. All patients tolerated the regimens well. RESULTS: The
      percentage of adequate clinical and parasitological response to mefloquine
      monotherapy was 62.0% in Mae Hong Son, 75.0% in Chiang Mai, 94.0% in Ratchaburi
      and 89.7% in Ubon Ratchathani. In Kanchanaburi, the percentage of adequate
      clinical and parasitological response to the artesunate-mefloquine combination
      was 94.2%. In the third group, this response exceeded 90%, except in Trat, where
      it was only 78.6% (44 patients). CONCLUSION: Mefloquine monotherapy must urgently
      be replaced in Mae Hong Son and Chiang Mai. The markedly reduced efficacy of the
      artesunate-mefloquine combination used in Trat raises questions about the future
      of this therapy on the southeastern border of Thailand with Cambodia. It is very
      worrying because no practical and affordable alternative is yet available.

PMID- 16451347
TI  - Distance to water source and altitude in relation to active trachoma in Rombo
      district, Tanzania.
AB  - OBJECTIVES: To investigate the relationship between distance to water source,
      altitude and active trachoma in children in Rombo district, Tanzania. METHODS: In
      each of Rombo's 64 villages, 10 balozis (groups of 8-40 households) were selected
      at random and all resident children aged 1-9 years were examined for clinical
      signs of active trachoma. The households of these children and village water
      sources were mapped using differentially corrected global positioning system data
      to determine each household's altitude and distance to the nearest water supply.
      RESULTS: We examined 12 415 children and diagnosed 1171 cases of active trachoma
      (weighted prevalence=9.1%, 95% CI: 8.0, 10.2%). Active trachoma prevalence ranged
      from 0% to 33.7% across villages. Increasing distance to the nearest water source
      was significantly associated with rising trachoma prevalence (age-adjusted odds
      ratio for infection (OR) for highest quartile compared to lowest=3.56, 95% CI
      2.47, 5.14, P for trend <0.0001). Altitude was significantly inversely associated
      with trachoma prevalence (age-adjusted OR for highest quartile compared to
      lowest=0.55, 95% CI 0.41, 0.75, P for trend <0.0001). These associations remained
      significant after adjustment in multivariate analysis. CONCLUSIONS: Trachoma is
      endemic in Rombo district, although the prevalence varies considerably between
      villages. Spatial mapping is a useful method for analysing risk factors for
      active trachoma.

PMID- 16451348
TI  - Financial implications of skilled attendance at delivery in Nepal.
AB  - OBJECTIVE: To measure costs and willingness-to-pay for delivery care services in
      8 districts of Nepal. METHOD: Household costs were used to estimate total
      resource requirements to finance: (1) the current pattern of service use; (2) all
      women to deliver in a health facility; (3) skilled attendance at home deliveries
      with timely referral of complicated cases to a facility offering comprehensive
      obstetric services. RESULTS: The average cost to a household of a home delivery
      ranged from 410 RS (5.43 dollars) (with a friend or relative attending) to 879 RS
      (11.63 dollars) (with a health worker). At a facility the average fee for a
      normal delivery was 678 RS (8.97 dollars). When additional charges, opportunity
      and transport costs were added, the total amount paid exceeded 5,300 RS (70
      dollars). For a caesarean section the total household cost was more than 11,400
      RS (150 dollars). Based on these figures, the cost of financing current practice
      is 45 RS (0.60 dollar) per capita. A policy of universal institutional delivery
      would cost 238 RS (3.15 dollars) per capita while a policy of skilled attendance
      at home with early referral of cases from remote areas would cost around 117 RS
      (1.55 dollars) per capita. These are significant sums in the context of a health
      budget of about 400 RS (5 dollars) per capita. Conclusions The financial cost of
      developing a skilled attendance strategy in Nepal is substantial. The mechanisms
      to direct funding to women in need must to be improved, pricing needs to be more
      transparent, and payment exemptions in public facilities must be better financed
      if we are to overcome both supply and demand-side barriers to care seeking.

PMID- 16451349
TI  - Determinants of skilled birth attendance in rural Cambodia.
AB  - OBJECTIVE: To identify the determinants of skilled and unskilled birth
      attendance. METHOD: Population-based survey in a rural area in Cambodia, of women
      aged 15-49 years who had delivered during the previous 3-month period. An
      analytical framework based on Andersen's behavioural model served to identify
      determinants according to delivery place (facility vs. non-facility), birth
      attendant at home births (skilled vs. unskilled), and change of birth attendant
      during delivery (changed vs. unchanged). We used logistic regression to analyse
      the data. RESULTS: Of 980 women included in the analyses, 19.8% had skilled
      attendants present during delivery. The determinants of facility delivery were
      different from those for having skilled attendants assisting in home births. In
      case of facility deliveries, previous contact with a skilled attendant through
      antenatal care was a significant determinant. In case of home births, the type of
      birth attendant (i.e. skilled or unskilled) at the preceding delivery was a
      significant determinant. CONCLUSION: Community-based programmes need to reach
      primiparas, because once a woman has delivered with the aid of an unskilled
      attendant, she is five to seven times less likely to seek skilled help than a
      primipara.

PMID- 16451350
TI  - Letter to the editors.

PMID- 16451351
TI  - Embryonic stem cells: similarities and differences between human and murine
      embryonic stem cells.
AB  - The derivation of murine embryonic stem (mES) cell lines was reported for the
      first time in 1981 (Nature, 1981; 292:154-156; Proc Natl Acad Sci U S A, 1981;
      78:7634-7638), and they have since proved to be a very useful tool with which to
      study mammalian development, which is characterized by pluripotency and
      differentiation. About 20 years later, the successful generation of human
      embryonic stem (hES) cell lines was described (Science, 1998; 282:1145-1147).
      Although mES and hES are derived from mammals, they cannot be looked at as being
      one and the same. While basic information for hES can be derived from mES, such
      information does not correspond on a one-to-one basis. This review gives an
      overview of the characteristics of embryonic stem cells with the main focus on
      the similarities and differences between human and mES cells.

PMID- 16451352
TI  - Increased interleukin-6 messenger RNA expression in macrophage-cocultured
      endometrial stromal cells in adenomyosis.
AB  - PROBLEM: To determine the effects of macrophage on endometrial stromal cells
      (ESCs) in women with adenomyosis. METHOD OF STUDY: Eutopic endometrium was
      obtained and separated into single ESC in 10 women with adenomyosis (study group)
      and 11 without adenomyosis (control group). ESCs were then cultured alone or with
      macrophage for 24 hr. RESULTS: Immunohistochemistry identified the presence of
      interleukin-6 (IL-6), IL-8, and IL-10 in ESCs. Real-time quantitative PCR
      revealed that the IL-6 mRNA was significantly expressed in macrophage-cocultured
      ESCs in adenomyosis than that in the controls, but was not different in ESCs
      cultured alone between the two groups. The levels of IL-8 and IL-10 mRNA were
      similar in ESCs either cultured alone or with macrophage between women with and
      without adenomyosis. CONCLUSION: IL-6 mRNA was significantly expressed in ESCs
      after in vitro coculture with macrophage in adenomyosis. This aberrant behavior
      of ESCs might play a role in the formation of ectopic endometrial implants in
      adenomyosis.

PMID- 16451353
TI  - Evidence for expression of both classical and non-classical major
      histocompatibility complex class I genes in bovine trophoblast cells.
AB  - PROBLEM: During the third trimester of pregnancy bovine trophoblast cells in the
      interplacentomal and arcade regions of the placenta express major
      histocompatibility complex class I (MHC-I) antigens. At parturition immunological
      recognition of MHC-I antigens appears to contribute to normal placental release.
      Therefore, we hypothesized that during late pregnancy bovine trophoblast cells
      express polymorphic, classical MHC-I antigens. METHOD OF STUDY: Cloning,
      microarray screening and sequencing of cDNA were used to study transcription of
      MHC-I genes in peripheral blood mononuclear cells (PBMC) and interplacentomal,
      trophoblast cells. Real-time reverse transcription, polymerase chain reaction (RT
      PCR) was used to compare the abundance of MHC-I transcripts in PBMC and
      trophoblast cells. RESULTS: Screening of cloned MHC-I cDNA on MHC-I microarrays
      indicated that in PBMC 90-98% of MHC-I transcripts were encoded by classical MHC
      I genes with the remainder encoded by non-classical MHC-I genes. In contrast, 21
      66% of MHC-I transcripts from interplacentomal trophoblast cells were from
      classical genes and 34-79% were from non-classical genes. Transcripts from four
      non-classical MHC-I loci were identified by sequence analysis. Real-time RT-PCR
      indicated that the overall levels of MHC-I gene expression in PBMC and
      trophoblast were similar. CONCLUSION: Bovine interplacentomal trophoblast cells
      express both classical and non-classical MHC-I genes, but the relative level of
      expression varies considerably.

PMID- 16451354
TI  - Autoantibodies in Argentine women with recurrent pregnancy loss.
AB  - PROBLEM: To determine the presence or absence of subclinical autoimmunity in
      Caucasian Argentine healthy women with first trimester recurrent pregnancy loss
      (RPL), the sera of 118 healthy women with a history of three or more consecutive
      abortions and 125 fertile control women without abortions and two children were
      analyzed for the presence of autoantibodies: immunoglobulin (Ig)G and IgM
      anticardiolipin, antinuclear (ANA), antismooth muscle (ASMA), antimitocondrial
      (AMA), antiliver-kidney-microsomal fraction (LKM), antigastric parietal cells
      (GPC), antineutrophil cytoplasmatic (ANCA) and antibodies antigliadin type IgA
      and IgG and IgA antitransglutaminase related with celiac disease (CD). METHOD OF
      STUDY: ANA, ASMA, AMA, anti-LKM, antibodies to GPC and ANCA were determined by
      indirect immunofluorescence (IFI) and anticardiolipin, antigliadina and
      antitransglutaminase antibodies were measured by enzyme-linked immunosorbent
      assays (ELISA). RESULTS: There was no significant difference between controls and
      patients with ANA, ASMA, AMA, LKM, ANCA and GPC. The prevalence of
      anticardiolipin antibodies in RPL was significantly higher than controls (P <
      0,01) and the prevalence of positive antibodies for antigliadina type IgA and IgG
      and IgA antitransglutaminase in RPL was significantly higher than controls (P <
      0.04). CONCLUSION: We show that Caucasian Argentine women with RPL showed
      significantly higher incidence of anticardiolipin antibodies than normal controls
      and finally we recommended the screening of IgA and IgG antigliadina and IgA
      antitransglutaminase antibodies in pregnancy, because of the high prevalence of
      subclinical CD in RPL and the chance of reversibility through consumption of a
      gluten free diet.

PMID- 16451355
TI  - A sandwich enzyme-linked immunoabsorbent assay for measurement of gonadotropin
      releasing hormone-toxin conjugates.
AB  - PROBLEM: Biological effectiveness of targeted cytotoxins is dependent on their
      stability, circulating half-life, receptor binding ability, and cytotoxicity. The
      objective of this study was to compare stability of gonadotropin-releasing
      hormone (GnRH)-toxin conjugates made with disulfide linkers to those using a
      maleimidodibutyryl (mb) linkage. METHOD OF STUDY: We developed a sandwich enzyme
      linked immunoabsorbent assay recognizing both GnRH analog and cytotoxin to ensure
      the conjugate measured was intact. Anti-D-Leu(6)-GnRH was used for capture and
      anti-pokeweed antiviral protein (anti-PAP) or anti-RNase for quantification.
      Specificity was verified by lack of reactivity with ovine FSH and LH, PAP, RNase,
      and D-Lys(6)-GnRH. RESULTS: Conjugates prepared using disulfide linkages were not
      stable in serum in vitro (half-lives <10 min), whereas mb conjugates had half
      lives >2 hr. Clearance of mbGnRH-PAP from the circulation of sheep was rapid
      (t(1/2) <20 min). CONCLUSION: The assays were found to be specific, sensitive and
      accurate for measurement of GnRH-toxin conjugates in vitro and in vivo.

PMID- 16451356
TI  - Short-term cytolytic mediators' expression in decidual lymphocytes is enhanced by
      interleukin-15.
AB  - PROBLEM: We investigated whether decidual adherent cells (DAC) and interleukin
      (IL)-15, in comparison to interleukin (IL)-2 affect cytolytic potential of first
      trimester decidual lymphocytes (DL). METHOD OF STUDY: Decidual mononuclear cells
      were obtained by enzymatic digestion and density gradient centrifugation. Non
      adherent DL were collected after 2-hr adherence and cultured for 18 or 72 hr
      with: IL-15 (0.5-5 ng/mL), IL-2 (100-1000 U/mL) or both of these cytokines, DAC
      (ratio 3:1 and 1:1) or DAC and anti-IL-15 antibody. Perforin, Fas ligand (FasL)
      and granzyme B were detected at mRNA level in indicated culture conditions.
      Cytolytic activity of DL against K-562, P815 and P815-Fas was measured by 2-hr
      PKH-26 cytotoxicity assay. The dynamics of perforin protein and mRNA expression
      were measured in DL after a contact with K-562 targets. RESULTS: Interleukin-15
      enhanced perforin, FasL and granzyme B transcription after 18-hr culture and
      prevented perforin protein downregulation, observed after DL culture. IL-2 had
      similar effects. DAC sustained perforin expression in DL and anti-IL-15
      monoclonal antibody abrogated this effect. DAC increased cytotoxicity of DL
      against K-562 which was mediated by IL-15. CONCLUSION: Interleukin-15, probably
      produced by DAC, upregulates cytolytic mediators' expression and perforin
      mediated cytotoxicity of DL, with equal efficiency as high concentrations of IL
      2.

PMID- 16451357
TI  - Elevation of macrophage colony-stimulating factor in amniotic fluid at late stage
      of normal pregnancy.
AB  - PROBLEM: Macrophage colony-stimulating factor (M-CSF) promotes placental growth
      and maintenance, and regulates trophoblast invasion into the placental bed. We
      evaluated whether the amniotic fluid M-CSF levels at the late stage of normal
      pregnancy is altered compared with those at the middle stage. METHOD OF STUDY:
      This study enrolled 52 subjects experiencing normotensive pregnancies with single
      fetuses, of whom 26 were women at the late stage (term gravidas) and 26 were
      women at the middle stage (controls). The average gestational age at entry was 38
      weeks of gestation and 17 weeks, respectively. Amniotic fluid was collected from
      these subjects. Amniotic fluid M-CSF levels were determined by the enzyme-linked
      immunosorbent assay method then compared between term gravidas and controls.
      RESULTS: Amniotic fluid M-CSF concentrations were 4815 pg/mL (median) in term
      gravidas and 3795 pg/mL in controls; the concentrations were significantly higher
      in term gravidas than in controls. CONCLUSIONS: We demonstrated a significant
      increase in amniotic fluid M-CSF levels in term gravidas. These results suggest
      that elevated levels of M-CSF in amniotic fluid have an important immunological
      function in the maintenance of pregnancy and fetal growth.

PMID- 16451360
TI  - Research utilization among dental hygienists in Sweden--a national survey.
AB  - Over the last decade evidence-based practice has become increasingly important in
      health care as an approach to improve patient outcomes. It is vital that dental
      hygienists, like other health professionals, use research findings to inform
      clinical practice. The objective of the present study was to investigate the
      extent of research utilization among dental hygienists in Sweden and to
      investigate the relationship between level of education and factors related to
      research utilization. A random sample of 261 dental hygienists in Sweden, 113
      with 1 year and 148 with 2-year education, responded to a postal questionnaire
      covering various aspects of research utilization, i.e. their attitudes towards
      research, availability and support for the implementation of research findings,
      use of research in daily practice, their activity in seeking new research
      findings and their participation in a range of research-related activities.
      Dental hygienists with 2-year education had a more positive attitude towards
      research, used research to a greater extent and were more active in seeking new
      research findings than dental hygienists with 1-year education. Overall,
      relatively few dental hygienists reported that they implemented research findings
      in practice; the most frequently reported activity concerned reading research
      articles in professional journals. The conclusions are that the length of dental
      hygiene education is a key factor influencing the application of research
      findings to practice. One-year education appears to be inadequate to achieve
      evidence-based practice. Moreover, not even two years of formal education
      guarantees necessary competence in research for evidence-based dental hygiene
      practice.

PMID- 16451358
TI  - High levels of peripheral blood NK cells in women suffering from recurrent
      spontaneous abortion are reverted from high-dose intravenous immunoglobulins.
AB  - PROBLEM: To determine the levels of peripheral blood natural killer (NK) cells in
      healthy women and recurrent aborters, and the effect of intravenous
      immunoglobulins (IVIGs) on these levels. METHOD OF STUDY: A total of 659 women
      were evaluated for NK cells by means of flow cytofluorimetry: 42 non-pregnant
      healthy women, 394 non-pregnant recurrent spontaneous abortion (RSA) women, 36
      pregnant healthy women and 187 pregnant RSA women. Fifty-four of the pregnant RSA
      women were treated with IVIG; in 18 of them NK cells were measured immediately
      before and after the very first IVIG infusion (0.5 g/kg body weight). RESULTS:
      Blood NK cell results were increased in RSA pregnant/non-pregnant women, and
      significantly reduced by IVIG, even after the very first infusion. In RSA
      pregnant women treated by means of IVIG therapy, 92.3% success rate was observed.
      CONCLUSIONS: High levels of NK cells are detected in women affected by RSA. IVIGs
      are capable of decreasing them with a short- and long-term efficacy, allowing
      having a very high success rate of pregnancies in RSA women.

PMID- 16451361
TI  - Assessing the prevalence of dental caries among elementary school children in
      North Korea: a cross-sectional survey in the Kangwon province.
AB  - OBJECTIVES: The lack of epidemiological studies has made it difficult to assess
      the extent of public health problems in North Korea. In the absence of empirical
      data, less intrusive study designs acceptable to the North Korean government
      could be developed to gauge the public's health. To this end we developed a basic
      oral health survey in order to assess the prevalence of untreated dental caries
      among children. METHODS: A cross-sectional survey of 854 elementary school
      students was conducted in the city of Wonsan, North Korea. Students were screened
      and classified into one of three states of oral health: no caries, minor caries
      or severe dental caries. Verbal surveys were concurrently administered on
      children to collect basic information on oral health behaviours and demographic
      characteristics. Statistical analyses were performed to determine if any
      variables were significant predictors of oral health status category. RESULTS:
      Among the 854 students screened, we found 255 students with no caries (29.9%),
      316 students with minor caries (37.0%), and 283 students with severe caries
      (33.1%). The majority of students (70.1%) screened had dental caries. Almost all
      of the students (98.5%) claimed to brush their teeth daily and 71.2% of students
      visited a dentist in the past year. There were no significant predictors of oral
      health status. CONCLUSIONS: The oral health of children in Wonsan, North Korea is
      comparable if not slightly better than the oral health status of children of
      similar age in countries with similar Social-Economic Status (SES). Basic oral
      health screens are useful to produce a snapshot of general oral health status
      among children in North Korea and may provide insight as to the general health of
      these children.

PMID- 16451362
TI  - Swedish dental hygienists' preferences for workplace improvement and continuing
      professional development.
AB  - The present study examined factors for workplace improvement and continuing
      professional development (CPD) for Swedish dental hygienists. Seventy-one per
      cent of 577 randomly selected members of Sweden's Dental Hygienist Association
      responded to a questionnaire. The chi-square test, Spearman's rank correlation,
      and multiple stepwise logistic regression modelling were used in the statistical
      analysis. The results showed that dental hygienists having more than 10 sick days
      annually and with a strong commitment to their work increased the preference for
      workplace improvements, such as peer recognition of dental hygienists'
      professional qualifications, clinical process quality, and time for reading
      research articles and participating in projects. In addition, dental hygienists
      in the 41-52 age group were associated with workplace improvements. This is in
      contrast to the factors that decreased preferences for workplace improvements:
      clear work roles, a 1-year training programme, a male clinic manager, and working
      in the private sector. Practicing dental hygiene in the public sector and
      lifestyle factors were the most influential determinants for a strong interest in
      CPD. CONCLUSION: Workplaces should observe people that are obviously committed to
      their work, those with many sick days, and those in a specific age group, as they
      indicate different preferences for workplace improvements. CPD seems to be a
      lower priority than workplace improvements for Swedish dental hygienists.

PMID- 16451363
TI  - Use of miswak versus toothbrushes: oral health beliefs and behaviours among a
      sample of Jordanian adults.
AB  - OBJECTIVE: This descriptive survey aimed at determining the perceived
      relationship among miswak, the toothbrush, and toothbrush-plus-miswak usage on
      oral health beliefs and behaviours of Jordanian adults, 18-60 years old, seeking
      dental care in the city of Irbid, northern Jordan. METHODS: Patients (n = 138)
      voluntarily completed a self-designed questionnaire prior to their dental
      appointments at public and private clinics. RESULTS: Overall, the level of oral
      health knowledge was low; of 71 people who attempted to define dental plaque,
      only 26% knew the meaning of dental plaque. While 12% have never been to a
      dentist, and 12% visit the dentist on a regular basis, the majority (63.2%) of
      the respondents reported that they visit the dentist only when they have pain.
      The majority (72%) use the toothbrush, 20.5% use the toothbrush-plus-miswak and
      only 3% use miswak alone. Toothbrush users believe that using the toothbrush-plus
      miswak is most effective in reducing mouth debris (chi2 = 32.069, d.f. = 16, P =
      0.01); and level of education is significantly associated with the type of oral
      cleaning device used (chi2 = 25.817, d.f. = 12, P = 0.05). There was no
      significant difference between toothbrush users and toothbrush-plus-miswak users
      in terms of how they perceive their oral health status. About 19% of the study
      participants use dental floss, 60.9% use mouth rinses and 8.3% use inter-dental
      brushes. Educated people (baccalaureate or associate degrees) tended to use
      toothbrushes and toothbrush-plus-miswak. The toothbrush-plus-miswak users are
      most likely to spend 1-2 min each day cleaning their teeth (chi2 = 34.9, d.f. =
      20, P = 0.02) than those using other devices. Respondents who use the toothbrush
      are most likely to visit the dentist when they have pain (chi2 = 34.02, d.f. =
      12, P = 0.00) than those using other devices. CONCLUSION: The oral health
      awareness level among Jordanian adults is poor and needs to be improved. Evidence
      based and community-based dental health education and a philosophical change from
      disease-oriented and pain management care to primary preventive care are highly
      recommended for the Jordanian population.

PMID- 16451364
TI  - Changes in the awareness of oral health among new students newly enrolled at the
      University of Tokyo over the past 15 years.
AB  - OBJECTIVE: The aim of this study was to examine changes in awareness of oral
      health among Japanese university students. METHODS: Between 1990 and 2004, a
      total of 51,650 students newly enrolled at the University of Tokyo responded to
      an annual written questionnaire on oral health. RESULTS: (i) Approximately 60% of
      the students brushed their teeth twice a day. Female students brushed more
      frequently than male students. (ii) The percentage of students who brushed for 2
      3 min per time decreased, while the percentage who brushed four or more minutes
      increased. (iii) The number of students who had learned how to brush properly
      increased. This trend was particularly clear-cut among male students, although
      the proportion of female students who had learned to brush properly remained
      higher than that of male students. (iv) The percentage of female students who
      sought treatment for malocclusion was higher than that of male students. The
      percentage of students who underwent orthodontic treatment increased from 11.6 to
      19.7%. The percentage of female students who received orthodontic treatment was
      approximately twofold that of male students. (v) The percentage of students who
      had temporomandibular disorders was 0.7% in males and 1.5% in females. (vi) More
      than 40% of the students had periodontal diseases, with a higher prevalence among
      male students than female students. (vii) Approximately 20% of the students
      wanted to consult our service centre. CONCLUSIONS: The awareness of oral health
      among new undergraduates at the University of Tokyo has improved over the past 15
      years.

PMID- 16451365
TI  - Independent dental hygiene practice worldwide: a report of two meetings.
AB  - OBJECTIVES: Following a meeting at the EUROPERIO in Berlin in 2003, a forum on
      Independent Practice of Dental Hygienists was held at the International Symposium
      on Dental Hygiene (ISDH) in Madrid July, 2004. The forum was organized and
      moderated by Beate Gatermann, President of the German Dental Hygiene Association.
      The participants were asked to address the following issues: population of
      country/state; population of dentists; population of state recognized dental
      hygienists (Canada/USA etc.); number of hygienists with 'Diploma' (Europe);
      duration of dental hygiene education; cost of education (2/3 year base
      approximately); when and how independent practice began in the country and who
      must be consulted or approve the application for an independent office (e.g.
      Health Department); what services are allowed? Can dental hygienists administer
      local anaesthesia in the dental office, and if so, must a dentist be present? Can
      dental hygienists purchase the necessary medication for the injection? Does the
      dental hygienist require additional education to provide local anaesthesia? How
      are the patients charged? Does the country offer a service fee list? Do insurance
      companies pay claims of the dental hygienist? What is the approximate average fee
      per hour charged (Euro/dollars)? Do dentists refer patients to you? If so, do
      they need a letter of referral? Are dental hygienists allowed to take radiographs
      in independent dental hygiene offices?

PMID- 16451366
TI  - The new food pyramid.

PMID- 16451370
TI  - Behavioural science in dentistry. The role of the dental hygienist in prevention
      and treatment of the fearful dental patient.
AB  - The prevalence of dental anxiety in the general population seems to be fairly
      stable, and the incidence is not reduced in spite of more modern treatment
      methods. Intensive fear often leads to avoidance of care and consequences like
      poor oral health, psychosocial problems and reduced quality of life. The
      aetiology of dental anxiety is complex, but is often associated with direct
      traumatic dental experiences during childhood. These negative experiences are
      reported as painful/unpleasant and are influenced by the patient's perception of
      lack of coping and control. The theory of latent inhibition indicates that
      several positive dental appointments before any invasive or painful treatment
      sessions may act as a barrier to these perceptions of lack of coping. This paper
      is presenting a short overview of behavioural science in dentistry and discussing
      the role of the dental hygienists as potential key personnel in prevention and
      treatment of dental anxiety.

PMID- 16451371
TI  - A study in vitro of the combined effects of soft drinks and tooth brushing with
      fluoride toothpaste on the wear of dentine.
AB  - The aim of this study was to measure loss of dentine produced by soft drinks
      alone and combined with tooth brushing with and without toothpastes. Groups of
      flat human dentine specimens were exposed for 10 min and then 30 min to orange
      juice (OJ), carbonated cola (CC) or modified blackcurrant (MB) drinks alone or
      after the exposures brushed with a fluoride toothpaste for 10 s. Further groups
      were exposed to OJ as before but brushed with water or non-fluoride toothpaste or
      placed in slurries of fluoride paste. Five cycles of each regimen were carried
      out. Tissue loss was determined by profilometry. Water immersion/brushing and
      brushing controls were included. OJ and CC produced similar erosion and
      significantly more than MB. Compared with drinks alone, dentine loss was reduced
      by fluoride toothpaste brushing but increased by water and non-fluoride
      toothpaste brushing. Fluoride toothpaste slurry had no significant effect on soft
      drink erosion. Very little abrasion with brushing alone was recorded over the
      time frame of these experiments. It is concluded that fluoride toothpaste could
      provide protection, albeit small, against erosion. The data again support the
      concept of brushing before meals.

PMID- 16451372
TI  - Factors related to oral hygiene in persons with scleroderma.
AB  - OBJECTIVES: The purpose of this study was to assess potential risk factors for
      the development of poor oral hygiene and increased dental caries in individuals
      with scleroderma. METHODS: Twenty-two subjects with scleroderma participated in
      this study. All subjects were examined with the Patient Hygiene Performance (PHP)
      Index, which assesses the extent of plaque and debris over a tooth surface. In
      addition, oral aperature, xerostomia and dominant upper extremity strength,
      motion, skin thickness, and dexterity were measured. RESULTS: None of the
      subjects had good or excellent hygiene. Fifteen subjects had fair oral hygiene
      and seven subjects had poor oral hygiene as measured by the PHP Index.
      Significant differences were seen between these two groups for oral aperture,
      percentage of teeth with caries, skin thickness, dexterity and finger flexion.
      Dexterity and joint motion correlated significantly with the number of decayed
      surfaces and number of caries. Oral aperture correlated with the PHP Index and
      the number of dental caries. CONCLUSIONS: Subjects with poor oral hygiene
      required more time to complete manual dexterity task and had decreased hand
      strength and joint motion. Moreover, these same subjects had more contractures,
      scars, ulcers, and higher skin scores (more disease activity) than subjects in
      the fair hygiene group. In addition to frequent dental exam and routine cleaning,
      dental personnel may want to consider exercises to increase oral aperature and
      investigate toothbrush and dental floss selection used by persons with
      scleroderma.

PMID- 16451373
TI  - An in vitro antimicrobial comparison of miswak extract with commercially
      available non-alcohol mouthrinses.
AB  - The aim of this study was to assess the antimicrobial activity of eight
      commercially available mouthrinses and 50% miswak extract against seven
      microorganisms. Corsodyl, Alprox, Oral-B advantage, Florosept, Sensodyne,
      Aquafresh Mint, Betadine and Emoform mouthrinses were used while 50% aqueous
      extract of miswak (Salvadora persica) was used against Streptococcus faecalis,
      Streptococcus pyogenis, Streptococcus mutans, Candida albicans, Staphylococcus
      aureus and Staphylococcus epidermidis. The ditch plate method was used to test
      the antimicrobial activity. Inhibition zones of microorganisms around ditches
      were measured in millimetres. Range, mean and standard deviations were used for
      comparison of antimicrobial activity. Mouthrinses containing chlorhexidine was
      with maximum antibacterial activity, while cetylpyridinium chloride mouthrinses
      were with moderate and miswak extract was with low antibacterial activity.
      Further research is needed for the substantivity of these mouthrinses and further
      in vivo/in vitro studies are needed using Biofilm model to substantiate present
      findings. Dental professionals must exercise caution and provide guidance in
      assisting their patients in making informed choices regarding their use of
      mouthrinses for clinical efficacy.

PMID- 16451374
TI  - Clinical studies to determine the effectiveness of a whitening toothpaste at
      reducing stain (using a forced stain model).
AB  - AIMS: Two single centre, randomized single-blind, crossover studies were
      performed, to compare the effect of a test toothpaste with a conventional
      fluoride paste in the inhibition and removal of extrinsic dental stain promoted
      by repeated chlorhexidine/tea rinses. METHODS: These studies used 24 subjects in
      each of two separate clinical trials. On the Friday before each trial period, the
      subjects received a prophylaxis to remove all staining, plaque and calculus
      deposits. On the following Monday, subjects were checked whether they were stain
      free and then under direct supervision they rinsed with a 0.2% chlorhexidine
      mouthrinse, immediately followed by a rinse with a warm black tea solution. This
      cycle was repeated hourly eight times throughout the day and on the following
      days until the Friday. In addition subjects also received daily a single
      toothpaste slurry rinse or control water rinse in the morning and lunchtime. No
      other form of oral hygiene was permitted during this period. On the Friday, both
      stain area and intensity was assessed using the Lobene Stain Index. For the stain
      removal study, stain was promoted again using chlorhexidine and tea rinses. After
      4 days, stain was measured both prior to and immediately after brushing with the
      allocated toothpaste for 2 min. Subjects were then instructed to use the
      toothbrush at home according to their normal oral hygiene practices. On the
      following Wednesday, the amount of stain present was re-assessed. Each subject
      subsequently received a thorough prophylaxis to remove all plaque calculus and
      staining before starting the following periods of the study. RESULTS: The study
      showed no difference in the ability of the test whitening toothpaste, control
      toothpaste and water control at inhibiting stain. There was also only a small
      difference (3.5% for product of area and intensity) between the ability of the
      two toothpastes to help remove stain after a single brushing. The difference was
      however in favour of the test product which approached a conventional level of
      significance (P = 0.089). There was no evidence of superiority for either of the
      pastes after normal home usage. CONCLUSIONS: This study has suggested that the
      test product may have some advantage over the conventional paste at removing
      stain but the magnitude of difference would appear to be small and of little
      clinical relevance.

PMID- 16451375
TI  - Mapping an appropriate health promotion approach for creches in an informal
      settlement.
AB  - BACKGROUND: People living in informal settlements in South Africa experience the
      double burden of poverty and ill health. Wallacedene, an informal settlement was
      highlighted in the media as being a socially and otherwise deprived community,
      with many accompanying health problems. AIM: It was against this background that
      this study was conducted to gain a better understanding of the health and oral
      health status of children attending creches in Wallacedene. It was designed to
      inform the mapping of an appropriate approach to develop a health promotion
      programme for creches. METHOD: Baseline data were collected through oral and
      general health examinations, site observations, a structured questionnaire and
      interviews with key people working with the children at two creches. RESULTS: The
      results indicate poor oral and general health. Gingival inflammation (82.8%),
      caries (81.5%), and moderate to abundant plaque deposits (95.7%), fungal
      infections (33.9%), runny nose (51.4%), lymphadenopathy (45.7%) and itchy skin
      (5.7%) were found. Caregivers were not well informed about oral health. However,
      they were enthusiastic to engage in new interventions. The community was
      impoverished; public health interventions were limited with minimal resources
      such as health centres and voluntary service providers. The limited resources
      were not coordinated and did not adequately address the health and educational
      needs of the children. CONCLUSION: A multi-sectoral approach focusing on
      community development is an appropriate approach to address the needs of creche
      children in this community.

PMID- 16451376
TI  - International employment in clinical practice: influencing factors for the dental
      hygienist.
AB  - PURPOSE: To assess demographics, job characteristics, geographical regions,
      resources and commitment, which influence dental hygienists seeking international
      clinical practice employment opportunities. METHODS: Questionnaires were mailed
      to a convenience sample of members of the Dental Hygienists' Association of the
      City of New York. Statistical analyses were conducted and frequency distributions
      and relationships between variables were calculated. RESULTS: Seventy-two percent
      of respondents reported that they are or may be interested in working overseas.
      Italy and Spain (67%) were the regions of most interest. Salary (65%) was cited
      as the most influencing factor in selection, whereas non-compliance with the
      equivalency to Occupational Safety and Health Administration standards (74%) was
      the most frequently perceived barrier. Multiple language fluency was
      statistically significant (0.003) regarding interest in overseas employment.
      CONCLUSION: Policy makers, employers and educators need to be aware of these
      findings should recruitment be a possibility to render urgently needed oral
      hygiene care in regions where there is a perceived shortage of dental hygienists.

PMID- 16451377
TI  - Diabetes in women.

PMID- 16451379
TI  - Is your knowledge up-to-date? Diabetic mellitus, type 1.

PMID- 16451382
TI  - Oral hygiene: past history and future recommendations.
AB  - Review of the dental literature reveals a changing emphasis attached to
      maintenance of optimal oral hygiene among patients over time. Moreover, a
      different relationship to this topic has been evident in the USA, Britain and
      Scandinavia. These changes, differences, and the rationale behind them, are
      described. The age of initiating oral hygiene practice and the optimal frequency
      of dental cleaning is discussed. Finally, recommendations are offered concerning
      oral hygiene promotion, both at the individual and community levels.

PMID- 16451383
TI  - A non-staining chlorhexidine mouthwash? Probably not: a study in vitro.
AB  - BACKGROUND AND AIM: Tooth staining is a common side effect of chlorhexidine mouth
      rinses and caused by the interaction of the di-cationic antiseptic with dietary
      chromogens. A product is now available, which claims an anti-discolouration
      system (ADS) with one clinical study in support. This study in vitro aims to
      determine whether two ADS rinses do or do not bind dietary chromogens. METHOD AND
      MATERIALS: Optically clear acrylic specimens were cycled through human saliva (2
      min), one of the three chlorhexidine rinses (two ADS and a positive control) (2
      min) or water and then soaked in tea (60 min). After each cycle the optical
      density (OD) of specimens were read on a UV/visible spectrophotometer. The exit
      point was the cycle at which OD was >2.0. RESULTS: All three rinses exceeded OD 2
      at 11 cycles and there was no significant difference in staining for the ADS
      rinses compared with the positive control rinse. CONCLUSION: Based on extensive
      literature for the correlation of this test in vitro with chlorhexidine anti
      plaque activity and propensity to stain in vivo these ADS rinses will have the
      same anti-plaque efficacy and potential to cause stain as established
      chlorhexidine rinse products.

PMID- 16451384
TI  - Tooth loss among habitual chewing-stick and plastic toothbrush users in the adult
      population of Mtwara, rural Tanzania.
AB  - OBJECTIVES: The aim of this study was to determine the extent and type of tooth
      loss in relation to habitual chewing-stick (CS) and plastic toothbrush (PT) users
      in adults. METHODS: A cross-sectional descriptive study was conducted in Mtwara's
      rural population aged >or=40 years. A total of 206 randomly selected study
      participants - males (55.8%) and females (44.2%) - were interviewed on oral
      hygiene practices using a structured questionnaire, and a clinical examination
      performed for assessment of tooth loss. RESULTS: Of the total, 93.2% were
      partially edentulous, 2.4% completely edentulous and those with no tooth loss
      4.4%. The total number of missing teeth were 1728 (mean, 8.38 +/- 7.9), and the
      causes were caries (74.9%), mutilation (4.8%) and others including periodontal
      and trauma (20.3%). There was no significant difference in the mean number of
      tooth loss between the upper and lower jaw, and between males and females.
      However, the mean number of missing teeth in the lower jaw was higher in females
      than in males (P = 0.04), and on lower left than lower right jaw (P = 0.008).
      Lower molars, especially first molars, were the teeth lost most often. Tooth
      cleaning devices included PT (51.5%), CS (25.7%), both type (BT; 17.0%) and
      unspecified (5.8%). The differences in the mean number of missing teeth were
      higher in CS than habitual PT users (P = 0.024) and in BT (P = 0.029). Tooth loss
      was also higher among those who brushed once when compared with those who brushed
      two times or more per day (P = 0.046). CONCLUSION: Tooth loss was significantly
      higher in CS than PT habitual users and affected mostly the lower molars and
      especially the first molar. However, for economical reasons, effective use of CS
      should be promoted for enhanced tooth retention.

PMID- 16451385
TI  - The use of the Internet to access oral health-related information by patients
      attending dental hygiene clinics.
AB  - BACKGROUND: The degree to which patients access the Internet for oral health
      related information is unknown. OBJECTIVES: This study was designed to determine
      if patients attending student dental hygiene clinics had: (1) accessed the
      Internet, (2) used the Internet as a source of information on both general health
      and oral health, (3) bought oral health care products on-line, and (4) were
      interested in being directed to appropriate on-line oral health resources by
      dental professionals. METHODS: A self-complete questionnaire was administered to
      a quota sample of 280 new and returning patients attending the student dental
      hygiene clinic at either the Cardiff Dental Hospital or a nearby Primary Dental
      Care Unit. RESULTS: A total of 269 (96%) patients consented to participate in the
      study. Of these, 147 (54.6%) had accessed the Internet, the majority (61.2%) from
      home. Internet use was significantly related to both patient age and level of
      education (P < 0.001). In total, 59 patients claimed accessing the Internet for
      information on general health topics. Only eight respondents had used the
      Internet for information on oral health/dental topics, with seven reporting that
      they found the information useful. On-line purchase of oral health products was
      reported by seven patients. However, 117 (43.5% of all respondents) patients
      indicated that they would be interested in the Internet as a future source of
      oral health information and 112 (41.6%) would appreciate being directed to
      appropriate sites by their dentist or dental hygienist. CONCLUSIONS: Patients
      attending student dental hygiene clinics make little use of the Internet for oral
      health information. However, reported interest in future access is such that
      dental professionals should develop and harness the potential of the Internet as
      an educational resource.

PMID- 16451386
TI  - Periodontal disease awareness among pregnant women and its relationship with
      socio-demographic variables.
AB  - Certain conditions may have an affect on gingival status and may aggravate pre
      existing disease, especially in persons with poor oral hygiene. Pregnancy is one
      of these conditions. In addition, there is evidence in the literature suggesting
      an association between periodontal diseases in pregnant women and giving birth to
      premature, low-birth infants. The purpose of this study was to evaluate the
      degree of periodontal health knowledge, and awareness, among pregnant women in
      Jordan. This was carried out by cross-sectional survey using self-administered,
      structured questionnaires distributed at six maternity care centres in Irbid
      City. Questionnaire items addressed personal and socio-demographic variables and
      periodontal health awareness and knowledge of pregnant women. Women (n = 300)
      were randomly chosen from attendants to these centres. Of the 300 questionnaires
      distributed, only 275 pregnant women ages 16-45 years with a mean of 29 year
      responded and were included in the study. Data were analysed by chi-squared test
      with the level of significance set at (P < 0.05). About one-third of the
      participants had secondary level of education; it appeared that a minority of the
      pregnant women had knowledge or ability to identify dental plaque (16.4%) and its
      harmful effects (22.5%), while most of them (88%) were aware that bleeding gums
      indicated the presence of periodontal disease. The differences in the responses
      to knowledge questions were only significant for question number one (What is
      plaque?) among different educational levels and groups. This study revealed that
      (71.6%) of the pregnant women knew the main cause of gum disease; however 56% of
      them do not believe that frequency of teeth brushing should be increased during
      pregnancy and only 5.1% believed there might be a relationship between gum
      diseases and premature labour. Knowledge and awareness for pregnant women about
      their teeth and gingival condition is generally poor. Pregnant women need
      accurate information about their teeth and oral health. Simple educational
      preventive programmes on oral self-care and disease prevention before and during
      pregnancy should be provided to improve oral health.

PMID- 16451387
TI  - Dental anxiety in children and its relationship to dental caries and gingival
      condition.
AB  - The aim of this study was to determine the levels of dental anxiety, dental
      caries and gingivitis among 12-15-year-old schoolchildren, in Irbid
      Governorate/northern Jordan, and to evaluate the correlation between these
      variables. Two schools were selected by a simple random method from each of the
      five geographic areas in Irbid Governorate. All children (1021), from the 10
      selected schools, who participated in this study completed a questionnaire
      modified from Kleinknecht's Dental Fear Survey (DFS questionnaire). Children
      underwent oral examination for dental caries and gingival condition, using
      Decayed, Missing and Filled Teeth (DMFT) Index and Loe and Silness Gingival Index
      (GI), respectively. Results of this survey showed that the prevalence of low to
      moderate 'general dental fear' among the study population was 43% while that of
      'high dental fear' was 10%. The self-reported 'general fear of dental treatment'
      was higher among girls than boys. Fear of specific stimuli (pain) was the most
      common source of dental fear. The sight and sensation of the anaesthetic needle
      and the sight, sound and sensation of the drill were rated the most fear
      eliciting stimuli. The mean DMFT (2.89) and GI (1.80) of boys was not
      significantly different from the DMFT (3.37) and GI (1.53) of girls (P > 0.05).
      Spearman's correlation test demonstrated no association between 'general dental
      fear' and dental caries (r = 0.06) or gingivitis (r = 0.007).

PMID- 16451388
TI  - Work stress and burnout among dental hygienists.
AB  - OBJECTIVES: The aim of this study was to describe the factors associated with
      work stress and burnout among dental hygienists. Furthermore, how to deal with
      work stressors in order to prevent burnout in the dental hygienist work
      environment will be discussed. METHODS: From a small literature search, only a
      few empirical studies could be traced that describe work stress or burnout among
      dental hygienists. RESULTS: Burnout incidence among dental hygienists appears to
      be relatively favourable, when compared with other professions, according to a 20
      year-old study. On the contrary, in a recent study, it was described that one out
      of eight dental hygienists felt emotionally exhausted from work. Dental
      hygienists, when compared with other professionals, are relatively negative about
      the variety of tasks they find in their work. Factors associated with experienced
      work stress are, according to another study, musculoskeletal pain, combining work
      and private life, highly efficient organization of work, long working hours,
      working without assistant, difficult or demanding patients, lack of leisure time,
      lack of support by practice management and doubts about one's own capabilities.
      Some factors that may prevent burnout are: recognition of one's own work
      pressure, learning to unwind, time management and organization of work, realistic
      career expectancies, social skills, healthy life-style, peer-group contacts and
      pre-graduate reflection. CONCLUSIONS: There appears to be a lack of recent data
      on burnout among dental hygienists. Although some knowledge exists on work
      stressors, a thorough investigation on burnout incidence, risk factors, as well
      as job resources is needed.

PMID- 16451389
TI  - Antioxidants in oral health care: making the connection.

PMID- 16451394
TI  - Sickle cell anemia in Guadeloupean children: pattern and prevalence of acute
      clinical events.
AB  - We analyzed the records of 153 Guadeloupean children with sickle cell anemia
      (SCA), for whom clinical and laboratory data were prospectively collected (mean
      follow-up duration 8.4 +/- 4.6 yr). Prevalence and age-specific frequencies of
      acute clinical events were determined and correlations between complications,
      hematological parameters and potential modulating factors investigated. Painful
      crisis and acute chest syndrome (ACS) were the two most common complications,
      affecting 65.4% and 58.8% of the patients, respectively. The frequency of acute
      anemia was 49.7% (acute splenic sequestration 24.8%; acute aplastic anemia
      15.0%). Prevalences of septicemia-meningitis and osteomyelitis were 15.7% and
      16.3%, respectively. A higher incidence of infections, painful crises and acute
      anemia was detected in patients who developed ACS. The well-documented protective
      effect of HbF level on the overall disease expression was observed with higher
      HbF level in asymptomatic than in symptomatic patients (17.5% +/- 8% vs. 9.9% +/-
      6.4%, P = 0.01) with similar ages and sex ratio. It was also confirmed on ACS
      and, for the first time, further extended to acute anemic events and septicemia.
      Besides its effect on hematological parameters, alpha-thalassemia seems to have
      little impact on the prevalence of complications, as do beta(S)-globin
      haplotypes. Comparison with other series suggests that the natural history of SCA
      in Guadeloupe is more similar to that in Jamaica with regard to those reported in
      Europe and the United States, suggesting a potential impact of environmental
      factors on the clinical course of the disease.

PMID- 16451393
TI  - Evaluation of the efficacy of oral deferiprone in beta-thalassemia major by
      multislice multiecho T2*.
AB  - OBJECTIVES: Oral deferiprone (L1) appears to be promising in the treatment of
      beta-thalassemia major (TM) patients. T2* magnetic resonance imaging (MRI) with a
      single measurement in the mid-ventricular septum was validated as a quantitative
      evaluation of myocardial iron overload. Previous studies suggested a marked
      heterogeneity of iron distribution in the myocardium. We set up a multislice
      multiecho T2* MRI for the detection of this heterogeneity. The aim of our study
      was to investigate differences between the L1 vs. the subcutaneous
      desferrioxamine (DF)-treated patients using this new approach. METHODS: Thirty
      six beta-TM patients (age 29 +/- 8 yr) underwent MRI. Eighteen patients received
      long-term L1, and 18 other patients matched for age and sex received DF. T2*
      multiecho sequences on three short axis views of the left ventricle were obtained
      and analyzed by custom-made software. In each slice, the myocardium was
      automatically segmented into four segments. Cine-dynamic images were also
      obtained to evaluate biventricular function. RESULTS: For multislice T2*
      technique, the coefficient of variation for intra- and inter-observer, and inter
      study reproducibility was 3.9%, 4.7%, and 5.5%, respectively. The global heart
      T2* value was significantly higher in the L1 vs. DF group (35 +/- 7 vs. 27 +/- 2
      ms; P = 0.02). The number of segments with normal T2* value (>20 ms) was
      significantly higher in the L1 vs. the DF group (11 +/- 1 vs. 8 +/- 5 segments; P
      = 0.03). We did not detect significant differences in biventricular function
      parameters. CONCLUSIONS: This new approach confirms that L1 could be more
      effective than DF in removal of myocardial iron.

PMID- 16451395
TI  - C-reactive protein level as a predictor of transient vs. sustained
      anticardiolipin antibody positivity.
AB  - The antiphospholipid (APLA) syndrome is defined as the occurrence of venous or
      arterial thromboembolism or recurrent fetal loss in patients with a positive
      anticardiolipin (aCL) or lupus anticoagulant test on two occasions, 3 months
      apart. In this study, we sought to determine whether the level of C-reactive
      protein (CRP), a non-specific inflammatory marker, at the time of the initial
      positive aCL test is a predictor of the transient vs. sustained nature of the
      aCL. Patients with a positive aCL antibody test underwent high sensitivity (hs)
      CRP testing. A repeat aCL antibody assay was performed on a serum sample obtained
      3-4 months later. The positive and negative predictive values of the hs-CRP assay
      as a predictor of the second aCL result were calculated and correlation between
      the hs-CRP result and second aCL result was determined. Fifty-four consecutive
      patients with a positive aCL test were studied. Forty-two had a positive aCL-2.
      The predictive value of a negative CRP test for a positive aCL-2 was found to be
      82.5% (33 of 42 patients). A positive CRP was able to predict a negative aCL-2 in
      35.7% of cases (nine of 14 patients). Our results suggest that the hs-CRP test
      may be useful in the assessment of patients with a positive aCL antibody test. A
      concurrently performed negative hs-CRP test result may be useful in making
      diagnostic and therapeutic decisions.

PMID- 16451397
TI  - Quantification of chimerism within peripheral blood, bone marrow and purified
      leukocyte subsets: comparison of singleplex and multiplex PCR amplification of
      short tandem repeat (STR) loci.
AB  - OBJECTIVE AND METHODS: Chimerism analysis has become a routine diagnostic
      procedure after haematopoietic allogeneic stem cell transplantation for early
      detection of relapse of disease or graft failure. Whereas some centres developed
      individual in-house short tandem repeat (STR) systems, others prefer commercial
      multiplex PCR systems. However, little is known about inter-assay variation,
      which could have a significant impact on treatment decision. We therefore
      compared two commercial multiplex PCR kits with our in-house STR system using
      different sample sources, such as peripheral blood (PB), bone marrow (BM) and
      specific leukocyte subsets. RESULTS: Fifty samples of eighteen paediatric
      patients were analysed. For neither material, PB, BM and leukocyte subtypes, a
      significant difference between the STR systems tested was observed. Chimerism
      analyses of each single STR primer, which is component of both the in-house and
      the commercial STR system, did not reveal significant differences. CONCLUSION:
      Our analysis demonstrates that similar results can be obtained with both assays,
      even when using various sample sources. Further evaluation of different test
      systems will help to increase interlaboratory standardisation of chimerism
      analyses for early clinical intervention.

PMID- 16451396
TI  - The length of treatment of aggressive non-Hodgkin's lymphomas established
      according to the international prognostic index score: long-term results of the
      GISL LA03 study.
AB  - OBJECTIVES: To compare two different schedules of two different anthracycline
      containing regimens, where length of treatment is modulated according to the
      international prognostic index (IPI) in patients with aggressive non-Hodgkin's
      Lymphoma (NHL). METHODS: In 1993 the Gruppo Italiano per lo Studio dei Linfomi
      (GISL) started a randomized 2 x 2 factorial phase III clinical trial for patients
      with newly diagnosed aggressive NHL comparing ProME(Epidoxorubicin)CE-CytaBOM (PE
      C) to ProMI(Idarubicin)CE-CytaBOM (PI-C) and a fixed to a flexible treatment
      schedule where anthracycline dose was to be modulated according to observed
      hematological toxicity. Patients with low or low-intermediate IPI (IPI 0-2) and
      those with intermediate-high or high IPI (IPI 3-5) should receive six or eight
      courses, respectively. Involved-field radiotherapy was allowed for patients with
      initial bulky disease or with residual masses. RESULTS: Three hundred and fifty
      six patients were registered into the study and randomized. Patients were well
      balanced among the four study arms in terms of clinical characteristics and
      prognostic factors. Three hundred and forty-five patients were available for
      evaluation of study endpoints. At the end of induction therapy complete remission
      rate was 61%, 5-year failure-free survival (FFS) rate was 40% and 5-year overall
      survival (OS) rate was 59%; no differences were observed according to treatment
      arms. Patients in the flexible arm received higher dose intensity of
      anthracycline (P < 0.001) with no apparent increase in toxicity. However, the
      flexible schedule was not superior to the fixed one. Patients with IPI 3-5 showed
      lower response rates (45% vs. 67%: P < 0.0001) and lower 5-year FFS (29% vs. 45%:
      P < 0.0001) compared to those with IPI 0-2. CONCLUSIONS: six courses of fixed or
      flexible PE-C or PI-C can determine a promising success rate in patients with
      advanced aggressive NHL with IPI 0-2, whereas the same regimens are less
      effective in patients with IPI 3-5, even if two additional courses are delivered.
      For the latter group of patients innovative approaches are warranted.

PMID- 16451398
TI  - Cyclosporine-responsive thrombocytopenia in a patient with chloramphenicol
      associated myelodysplastic syndrome.
AB  - A 64-yr-old patient with myelodysplastic syndrome (MDS), with refractory
      cytopenia with multilineage dysplasia subtype following chloramphenicol exposure
      received immunosuppressive treatment with antithymocyte globulin and cyclosporine
      (CsA). Complete remission was achieved and CsA was tapered after 2.5 yr. Shortly
      after CsA withdrawal, the patient relapsed with thrombocytopenia but responded to
      restoration of CsA. This case illustrates that immune-mediated mechanisms of
      cytopenia in MDS may be dependent on continued immunosuppressive treatment
      similar to aplastic anemia.

PMID- 16451399
TI  - Marrow aplasia developing 13 years after HLA-identical sibling allogeneic
      transplantation for chronic myeloid leukaemia: successful treatment with
      antithymocyte globulin and peripheral blood stem cell infusion from the original
      donor.
AB  - Secondary or late graft failure has been defined as the development of inadequate
      marrow function after initial engraftment has been achieved. We describe a case
      of profound marrow aplasia occurring 13 years after sibling allogeneic bone
      marrow transplantation for chronic myeloid leukaemia (CML) in first chronic
      phase. Although the patient remained a complete donor chimera, thereby suggesting
      that an unselected infusion of donor peripheral blood stem cells (PBSC) or bone
      marrow might be indicated, the newly acquired aplasia was thought to be immune in
      aetiology and some immunosuppression was therefore considered appropriate. Rapid
      haematological recovery was achieved after the infusion of unselected PBSC from
      the original donor following conditioning with anti-thymocyte globulin (ATG).

PMID- 16451400
TI  - Complete donor chimaerism of Langerhans cells in lymph node early after
      allogeneic bone marrow transplantation.
AB  - Host-derived Langerhans cells (LCs) are crucial antigen-presenting cells that
      cause graft-vs.-host disease after allogeneic haematopoietic stem cell
      transplantation (HSCT). However, chimaerism of LCs after allogeneic HSCT is
      largely unknown in humans. We here report a case that developed dermatopathic
      lymphadenitis accompanied by an accumulation of donor-derived LCs in the second
      month after allogeneic HSCT with reduced-intensity conditioning. This is the
      first case to show that donor LCs have the ability to migrate into draining lymph
      nodes and replace host LCs early after HSCT in humans.

PMID- 16451401
TI  - Cutaneous leucoclastic vasculitis (LV) following bortezomib therapy in a myeloma
      patient; association with pro-inflammatory cytokines.
AB  - The proteasome inhibitor, bortezomib, has anti-myeloma activity even in myeloma
      cells refractory to multiple prior treatments. Bortezomib blocks the production
      of nuclear factor-kappaB (NFkappaB)-mediated pro-inflammatory cytokines. We
      report a patient with myeloma who developed a cutaneous leucoclastic vasculitis
      (LV) after bortezomib treatment. The patient with LV exhibited a marked increase
      in serum levels of IL-6, TNF-alpha, and C-reactive protein (CRP). Bortezomib
      administration may enhance the release of pro-inflammatory cytokines, which might
      play a role in bortezomib-induced cutaneous LV.

PMID- 16451402
TI  - Life-threatening interaction between antiretroviral therapy and vinblastine in
      HIV-associated multicentric Castleman's disease.
AB  - BACKGROUND: HIV-infected patients still present a high risk of developing
      lymphoproliferative malignancies, despite the fact that their prognosis has been
      considerably improved by highly active antiretroviral therapy (HAART). Potential
      interactions exist between antiretroviral drugs, in particular protease
      inhibitors, and anti-neoplastic ones, but their impact in terms of clinical and
      haematological adverse events remains unclear. METHODS: We report a case of
      potentially life-threatening interaction between vinblastine and antiretroviral
      therapy in a patient presenting with HIV-associated multicentric Castleman's
      disease (MCD). RESULTS: A 55-year-old HIV-1 infected patient was diagnosed with
      MCD while being treated with a salvage HAART regimen consisting of zidovudine,
      lamivudine, abacavir, nevirapine and ritonavir-boosted lopinavir. Vinblastine was
      prescribed as a monotherapy at the usual dose of 6 mg/m2 (i.e. 10 mg) every 3
      weeks. The first vinblastine course was performed without HAART with no adverse
      event. Antiretroviral therapy was resumed for the two following courses which
      were associated with unexpected severe digestive and haematological toxicities,
      and moderate renal failure. Vinblastine was then administered alone at increasing
      doses without toxicity. HAART was finally resumed and we assessed that a
      decreased vinblastine dose of 2 mg/m2 was well tolerated, with a complete
      response of MCD. CONCLUSIONS: HAART regimen comprising protease inhibitors, which
      are potent inhibitors of cytochrome P450 and P-gp, could interfere with anti
      neoplastic drugs, as demonstrated with vinblastine in our case report.

PMID- 16451404
TI  - Diagnostic approaches for immunocompromised paediatric patients with pulmonary
      infiltrates.
AB  - Pulmonary infiltrates in immunocompromised children often pose problems in terms
      of deciding on further diagnostic and therapeutic procedures, but few studies
      have evaluated the value of non-invasive and invasive diagnostic methods in
      paediatric populations. Both galactomannan ELISA and PCR protocols appear to be
      less useful in children than in adults. Invasive procedures, such as
      bronchoalveolar lavage or lung biopsy, can yield a pathohistological diagnosis
      and/or the isolation of a pathogen. Prospective studies in paediatric patients
      are needed urgently to assess the value of different diagnostic procedures and to
      define an effective and safe diagnostic strategy for the individual child.

PMID- 16451405
TI  - Herpes simplex virus infection, with particular reference to the progression and
      complications of primary herpetic gingivostomatitis.
AB  - Primary herpetic gingivostomatitis (PHGS) represents the clinically apparent
      pattern of primary herpes simplex virus (HSV) infection, since the vast majority
      of other primary infections are symptomless. PHGS is caused predominantly by HSV
      1 and affects mainly children. Prodromal symptoms, such as fever, anorexia,
      irritability, malaise and headache, may occur in advance of disease. The disease
      presents as numerous pin-head vesicles, which rupture rapidly to form painful
      irregular ulcerations covered by yellow-grey membranes. Sub-mandibular
      lymphadenitis, halitosis and refusal to drink are usual concomitant findings.
      Following resolution of the lesions, the virus travels through the nerve endings
      to the nerve cells serving the affected area, whereupon it enters a latent state.
      When the host becomes stressed, the virus replicates and migrates in skin,
      mucosae and, in rare instances, the central nervous system. A range of
      morbidities, or even mortality, may then occur, i.e., recurrent HSV infections,
      which are directly or indirectly associated with PHGS. These pathological
      entities range from the innocuous herpes labialis to life-threatening
      meningoencephalitis.

PMID- 16451407
TI  - Risk of bacteraemia and mortality in patients with haematological malignancies.
AB  - This study examined the association between type of haematological malignancy,
      risk of bacteraemia and risk of mortality, with emphasis on the impact of
      bacteraemia type on mortality. A population-based cohort design was used, and all
      patients aged > or = 15 years with an incident haematological malignancy who were
      living in North Jutland County, Denmark, during 1992-2002 were included in the
      study. Among 1666 patients with an incident haematological malignancy, 358 (21%)
      suffered an episode of bacteraemia during a median follow-up period of 1.1 years
      (quartile 0.2-3.4) from the date of cancer diagnosis (overall incidence rate of
      96/1000 person-years). In comparison to Hodgkin's disease, adjusted incidence
      rate ratios (IRRs) were 23.3 (95% CI, 10.0-54.5) for acute myeloid leukaemia, 3.8
      (95% CI, 1.5-9.3) for multiple myeloma, and 2.2 (95% CI, 0.9-5.1) for non
      Hodgkin's lymphoma or chronic lymphatic leukaemia. Overall cumulative 30-day
      mortality was 32% (95% CI, 27-37), and 90-day mortality was 50% (95% CI, 44-55).
      In comparison with acute myeloid leukaemia, adjusted mortality rate ratios (MRRs)
      were close to 1.0 for other haematological malignancies. In comparison to
      bacteraemia caused by Gram-positive bacteria, adjusted MRRs were 1.0 (95% CI, 0.6
      1.5) for Gram-negative bacteraemia, and 1.9 (95% CI, 1.1-3.3) for polymicrobial
      bacteraemia or fungaemia. Thus, the risk of bacteraemia varied greatly according
      to the type of malignancy, while mortality rates were similar for these diseases,
      although dependent on the type of bacteraemia. Polymicrobial bacteraemia or
      fungaemia was associated with higher mortality.

PMID- 16451406
TI  - Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer
      patients.
AB  - Combination therapy with a beta-lactam plus an aminoglycoside has been the
      standard approach for treating febrile neutropenia for many years. More recently,
      beta-lactam monotherapy has also been shown to be a reliable and safe approach.
      In the present study, 763 eligible patients with fever and neutropenia received
      piperacillin-tazobactam monotherapy. On day 3, according to the study protocol,
      165 patients with persistent fever who fulfilled the study entry criteria were
      randomised to receive vancomycin or a placebo. The success rate was 51% in the
      intention-to-treat analysis and 62% in the per-protocol analysis. The overall
      mortality rate was 8% (58/763), with only 18 (2.4%) deaths attributed to the
      initial or subsequent infection. Randomisation had no influence on the study
      endpoints. The adverse event rate was evaluated only in the patient population
      not included in the randomised part of the study. Among these patients, adverse
      events probably or definitely related to piperacillin-tazobactam therapy were
      uncommon, confirming the favourable safety profile of piperacillin-tazobactam. It
      was concluded that piperacillin-tazobactam could be considered as monotherapy for
      patients with high-risk febrile neutropenia.

PMID- 16451408
TI  - Population-based surveillance of invasive pyogenic streptococcal infection in a
      large Canadian region.
AB  - Pyogenic streptococci are a major cause of invasive infection. This study
      presents the results of a population-based laboratory surveillance for invasive
      pyogenic streptococcal infections among residents of the Calgary Health Region
      (population 1 million) between 1 July 1999 and 30 June 2004. The overall annual
      incidence rate was 18.65/100,000 population, with isolates belonging to the
      Streptococcus milleri group forming the most important aetiology (incidence of
      8.65/100,000 population). Invasive infection with groups A, B, G and C
      streptococci occurred at annual rates of 4.27, 3.13, 1.83 and 0.41/100,000
      population, respectively. There was a close relationship between increasing age
      and development of an invasive pyogenic streptococcal infection, and the
      incidence of infection was higher among males than among females. Differences in
      the seasonal occurrence and focus of infection occurred between the different
      groups.

PMID- 16451409
TI  - Pneumocystis jirovecii colonisation in patients with interstitial lung disease.
AB  - A prospective study was conducted to determine the prevalence of colonisation by
      Pneumocystis jirovecii in 80 consecutive patients who required bronchoscopy and
      bronchoalveolar lavage (BAL) following suspicion of interstitial lung disease
      (ILD). The mtLSU rRNA gene of P. jirovecii was identified by nested PCR in BAL
      samples. Patients with ILDs were divided into three groups: group A comprised
      those with idiopathic interstitial pneumonias; group B comprised those with
      sarcoidosis; and group C comprised those with other ILDs. The overall prevalence
      of P. jirovecii carriage was 33.8%, with colonisation rates of 37.8%, 18.8% and
      37% in groups A, B and C, respectively (p not significant). There were more
      smokers among the carriers, but there were no other significant differences
      between carriers and non-carriers. The high prevalence of P. jirovecii carriers
      found among immunocompetent patients with ILDs in Spain suggests a possible role
      of P. jirovecii in the natural history of these diseases.

PMID- 16451410
TI  - IgA antibodies in persisting Helicobacter pylori infection in Finnish adults.
AB  - Most individuals infected with Helicobacter pylori have elevated levels of
      specific IgG antibodies, but only in about two-thirds of cases does the IgA titre
      exceed the cut-off level. The aim of this study was to determine whether H.
      pylori-infected subjects with elevated IgG levels would subsequently produce IgA
      antibodies, and whether elevated IgA levels increased during infection. Paired
      sera were available from 336 adults who took part in a large population-based
      health survey in 1977-1980 and a follow-up study on asthma and atopic diseases in
      1997-1998 (series A). Data on paired sera from 224 adults who participated in a
      population-based health survey in Vammala, Finland in 1973 and who gave a follow
      up blood sample in 1994 (series B) were also re-analysed. H. pylori IgG and IgA
      levels were determined with commercially available (series A) and in-house
      (series B) enzyme immunoassays. Twenty-one (35%) of the 60 subjects who initially
      had elevated levels of IgG antibodies only were found to be IgA-positive at
      follow-up. In those subjects whose baseline and follow-up samples were IgG- and
      IgA-positive, the median IgA levels increased by 48% and 22% in series A and B (p
      < 0.0001 and p 0.0241), respectively, whereas the median IgG levels did not
      change significantly in either series. During H. pylori infection, an increase in
      specific IgA was reflected by the increase in the number of responders and by the
      rise in titres.

PMID- 16451411
TI  - Alert surveillance of intensive care unit-acquired Acinetobacter infections in a
      Sicilian hospital.
AB  - The epidemiological impact of Acinetobacter baumannii nosocomial infections in a
      Sicilian intensive care unit (ICU) was investigated to determine the
      Acinetobacter-specific infection rates, to estimate the preventable proportion of
      Acinetobacter infections, i.e., those resulting from cross-transmission, and to
      investigate the molecular epidemiology of antimicrobial resistance in
      Acinetobacter. The impact of Acinetobacter nosocomial infection in the ICU was
      determined to be 3.0 new cases per 100 admissions. Site-specific rates confirmed
      that ICU-acquired pneumonia was the most important infection type. The incidence
      rate, adjusted by the number of patient-days, was 3.3 infections/1000 patient
      days. The estimated preventable proportion of A. baumannii nosocomial infections
      in the ICU was 66.7%. A class 1 integron, characterised by its gene cassette
      content, was present in all A. baumannii isolates of four different pulsed-field
      gel electrophoresis types, and was associated significantly with clones
      implicated in cross-transmission episodes. Furthermore, the same integron was
      detected in two genetically distinct isolates responsible for recurrent infection
      in the same patient, suggesting the occurrence of horizontal gene transfer in
      vivo. Even in an endemic setting with low infection rates, spread of A. baumannii
      was caused mainly by infection control shortcomings that require appropriate
      surveillance and control policies.

PMID- 16451412
TI  - Selection of an Escherichia coli O157:H7 bacteriophage for persistence in the
      circulatory system of mice infected experimentally.
AB  - A bacteriophage lytic for Escherichia coli O157:H7 was isolated from bovine
      manure. Following in-vivo selection, the phage acquired the capacity to persist
      in the circulatory system of mice for at least 38 days. When mice were infected
      experimentally with E. coli O157:H7 (10(7) CFU/mouse), simultaneous injection of
      the mice with phage (10(8) PFU/mouse) cleared E. coli O157:H7 from the mice
      within 48 h.

PMID- 16451414
TI  - Characterisation of non-multiresistant methicillin-resistant Staphylococcus
      aureus (including EMRSA-15) in Kuwait Hospitals.
AB  - This study characterised non-multiresistant methicillin-resistant Staphylococcus
      aureus (nmMRSA) isolates from Kuwait hospitals to ascertain whether they were
      community-acquired MRSA (CA-MRSA). Forty-two nmMRSA isolates obtained between
      July 2001 and October 2003 were analysed by staphylococcal cassette chromosome
      mec (SCCmec) typing, bacteriophage typing, production of Panton-Valentine
      leukocidin (PVL), urease and staphylococcal enterotoxins A, B, C and D, TSST-1,
      and by pulsed-field gel electrophoresis (PFGE). Forty-one isolates were SCCmec
      type IV, and one isolate was SCCmec type III. The isolates belonged to six PFGE
      patterns, with two types, A and D, distributed in six and four hospitals,
      respectively. Most (n = 26; 61.9%) isolates produced urease. These isolates were
      mainly from wound and skin infections, showed low-level methicillin resistance
      (MIC 8-48 mg/L), and nine carried genes for PVL. These characteristics, together
      with their carriage of the type-IV SCCmec, identified the isolates as CA-MRSA.
      Ten of the 16 urease-negative isolates produced staphylococal enterotoxin C; 12
      reacted weakly with phage 75, and were resistant to clindamycin and/or
      erythromycin, which are characteristics of EMRSA-15. Thus, this study identified
      the co-existence of two types of nmMRSA, i.e., CA-MRSA and EMRSA-15, in Kuwait
      hospitals.

PMID- 16451415
TI  - Genetic analysis of a multiresistant strain of Pseudomonas aeruginosa producing
      PER-1 beta-lactamase.
AB  - A multiresistant strain of Pseudomonas aeruginosa, PA2345, belonging to serotype
      O:1, was isolated at the Teaching Hospital of Besancon, France. Resistance to
      beta-lactams, including third-generation cephalosporins, depended upon a
      chromosomally-located composite transposon carrying the bla(PER-1) gene encoding
      extended-spectrum beta-lactamase PER-1. PA2345 was unrelated genotypically to two
      previous PER-1-producing isolates of P. aeruginosa. Sequence analysis of the
      transposon in PA2345 revealed the presence of two insertion sequences (ISPa23 and
      ISPa24) with very different predicted transposases (TnpA1, TnpA2), which were
      both bordered by closely related 16-bp inverted repeats. High resistance of
      PA2345 to aminoglycosides was caused, in part, by a chromosomal class-I integron
      containing gene cassettes aadB, encoding an ANT(2'') enzyme, and aadA11, encoding
      a new ANT(3'') enzyme with 281 amino-acids that conferred elevated resistance to
      streptomycin and spectinomycin. Stable overproduction of efflux system MexXY
      contributed to resistance to amikacin, while mutations in the quinolone
      resistance-determining regions of gyrA and parC accounted for the high resistance
      of PA2345 to fluoroquinolones. The study indicates that multidrug resistance in
      P. aeruginosa might arise from sequential acquisition of a variety of mechanisms
      provided by both horizontal gene transfers and mutations in chromosomal genes.

PMID- 16451413
TI  - Genetic diversity of Legionella pneumophila inferred from rpoB and dotA
      sequences.
AB  - This study characterised the population structure of Legionella pneumophila by
      comparing the rpoB (300-bp) and dotA (360-bp) sequences of 267 isolates (18
      reference strains, 149 Korean isolates and 100 Japanese isolates). In addition to
      the six clonal subgroups established previously, four subgroups, P-V to P-VIII,
      were identified. Subgroupings based on rpoB and dotA sequences were found to
      correlate with the source of the isolates, and this data may be useful for future
      epidemiological studies. Fourteen (five Korean and nine Japanese) isolates showed
      incongruent subgroupings in the rpoB and dotA trees, suggesting that genetic
      exchange among subgroups, and even among subspecies, may occur frequently in
      nature.

PMID- 16451416
TI  - Risk-factors for acquisition of extended-spectrum beta-lactamase-producing
      Escherichia coli among hospitalised patients.
AB  - Between 1996 and 2002, 103 hospitalised patients yielding one or more clinical
      isolates of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC)
      were identified. A significant increase was observed in the incidence of ESBL-EC
      colonisation or infection during the study period (1.65 episodes/100 000 patient
      days in 1996 to 12.6 episodes/100 000 patient-days in 2002; p 0.01). Infection
      developed in 70 (68%) patients (75 episodes), with surgical site (44%) and
      urinary tract (17%) infections being the most frequent. Pulsed-field gel
      electrophoresis showed extensive clonal diversity among the isolates. A case
      control study and multivariate analysis identified female gender (OR 2.1; p
      0.01), use of a nasogastric tube (OR 3.5; p 0.001) and previous antibiotic
      therapy (OR 3.9; p < 0.001) as independent variables associated with acquisition
      of ESBL-EC. The study demonstrated a progressive increase in the number of ESBL
      EC isolates in a non-epidemic setting. Most cases of ESBL-EC colonisation or
      infection occurred in hospitalised patients exposed to invasive procedures and
      antibiotic pressure.

PMID- 16451417
TI  - Characterisation of the first CTX-M-10-producing isolate of Salmonella enterica
      serotype Virchow.
AB  - Microbiological analysis of a urine sample from an outpatient with symptoms of
      urinary infection detected >10(5) CFU/mL urine of Salmonella enterica serotype
      Virchow with resistance to cefotaxime. Molecular analysis demonstrated the
      presence of the gene encoding CTX-M-10 beta-lactamase in this clinical isolate.
      This is the first report of this enzyme in Salmonella spp.

PMID- 16451418
TI  - Adults with spontaneous aerobic Gram-negative bacillary meningitis admitted to
      the intensive care unit.
AB  - The characteristics of spontaneous aerobic Gram-negative bacillary meningitis
      (AGNBM) were determined in 40 adults requiring admission to an intensive care
      unit (ICU) during a 16-year period in ten French ICUs. Eight infections were
      hospital-acquired and most patients had predisposing factors, mainly chronic
      alcoholism and an immunocompromised status. Three immunosuppressed patients had
      disseminated strongyloidiasis. Gram's stain, cerebrospinal fluid and blood
      cultures were positive for 85%, 98% and 80% of cases, respectively. Escherichia
      coli (57%) and Klebsiella pneumoniae (17%) were the most frequent pathogens. In
      ICU mortality was 38%. Spontaneous AGNBM is a rare complication of bacteraemia in
      adults. The severity of predisposing underlying diseases might explain the poor
      prognosis despite appropriate antimicrobial therapy.

PMID- 16451419
TI  - Influence of hepatitis C and hepatitis G virus co-infection on viral and cellular
      dynamics in patients infected with human immunodeficiency virus following
      interruption of highly active anti-retroviral therapy.
AB  - This study describes the influence of hepatitis C virus (HCV) and hepatitis G
      virus (HGV) co-infection on CD4 cell count decline and plasma human
      immunodeficiency virus (HIV) viral load in HIV-infected patients during a 1-year
      period following interruption of highly active anti-retroviral therapy (HAART)
      guided by CD4 count. CD4 cell count decline and plasma HIV viral load did not
      differ between HIV mono-infected patients and those patients co-infected with HCV
      and HGV. HCV genotype 1 had no apparent influence on the cellular and viral
      dynamics in HIV-infected patients compared with other HCV genotypes, although the
      unbalanced groups make larger studies desirable.

PMID- 16451421
TI  - Changes in macrolide resistance among respiratory pathogens after decreased
      erythromycin consumption in Taiwan.
AB  - Measures to alleviate the growing problem of macrolide resistance in Taiwan
      resulted in a decrease in macrolide consumption, from 0.629 defined daily
      doses/1000 inhabitants per day (DIDs) in 1999 to 0.301 DIDs in 2003 (a reduction
      of 52%). A linear relationship was observed between the decline in erythromycin
      consumption and the decline in erythromycin resistance in Streptococcus pyogenes
      (46% in 1999 vs. 17% in 2003; p < 0.001) and azithromycin resistance in
      Haemophilus influenzae (31% in 2000 vs. 0% in 2003; p < 0.001). However, the rate
      of erythromycin resistance in Streptococcus pneumoniae showed a continued
      increase, from 80.2% in 1999 to 92% in 2003.

PMID- 16451420
TI  - Comparison of redox and D29 phage methods for detection of isoniazid and
      rifampicin resistance in Mycobacterium tuberculosis.
AB  - Rapid, accurate and inexpensive methods are essential to detect drug-resistant
      Mycobacterium tuberculosis and allow timely application of effective treatment
      and precautions to prevent transmission. The proportion method, the MTT and
      Alamar Blue redox methods, and the D29 mycobacteriophage assay, were compared for
      their ability to detect resistance to isoniazid and rifampicin. When tested
      against a panel of known M. tuberculosis strains, the redox methods and the D29
      assay showed good sensitivity and specificity compared to the proportion method,
      suggesting that they could be useful alternatives for identifying multidrug
      resistance in M. tuberculosis.

PMID- 16451422
TI  - Disseminating research internationally.

PMID- 16451423
TI  - The impact of sleep interruptions on vital measurements and chronic fatigue of
      female caregivers providing home care in Japan.
AB  - The purposes of this study were to examine the impact of sleep interruptions on
      diurnal changes in blood pressure and chronic fatigue in middle-aged and elderly
      caregivers by using a cross-sectional quantitative method. Thirty-five female
      caregivers who were not taking antihypertensive and/or sleeping drugs were
      recruited for this study. Blood pressure was monitored over a 24 h period.
      Sleeping or waking periods were monitored with an actigraph. Fatigue was
      determined from a self-administered questionnaire. Participants were classified
      into four groups by cause of sleep interruption. One-way analysis of variance
      showed no differences in blood pressure, but hypertension was prevalent (40%).
      Sleep duration differed significantly, with the longest duration for those
      scheduled to wake up for care. Substantial variations were identified in the
      eight subcategories of chronic fatigue, with those without sleep interruption
      having the worst profile. This suggests that multiple factors in addition to
      sleep interruption affect the care burden.

PMID- 16451424
TI  - Concept analysis of coping with arthritic pain by South Korean older adults:
      development of a hybrid model.
AB  - This study was conducted to clarify and conceptualize the phenomenon of coping
      with arthritic pain by older adults. The Hybrid Model of concept development was
      applied to develop a conceptual structure of coping with arthritic pain by older
      adults. A refined definition of coping with arthritic pain by older adults
      emerged that identified the attributes and structure of the concept. This study
      reveals the characteristics of the ways that older adults cope with arthritic
      pain, such as how they experience themselves, how pain affects their daily life,
      and how they perceive the meaning of coping with arthritic pain. These
      characteristics indicate the complexity of the concept regarding the coping of
      older adults with arthritic pain. This area needs to be clarified when nursing
      staff assess coping with pain and plan pain management for older adults.

PMID- 16451425
TI  - The art of professional development and caring in cancer nursing.
AB  - The impetus for this qualitative study was the premise expressed by lay people
      that nursing terminally ill cancer patients must be depressing and difficult to
      cope with. Its focus was nurses' stress and coping strategies, both secular and
      religious. Data was collected using a narrative life-story approach, and then
      Lazaruz and Folkman's coping theory and Pargament's theory on the psychology of
      religion were used during the analysis of the data. Several factors were
      identified, related to the individual and group levels, that influence a nurse's
      identity and professional development. A person's life orientation was suggested
      as a first concept for developing a professional paradigm that includes caritas
      as a main orienting factor. Directed by the nurse's secular and religious
      orientation, competence develops, making it possible to understand, analyze,
      manage, and appreciate the significance of the professional work of caring.

PMID- 16451426
TI  - Comparison of knowledge, attitudes, experience, and opinions between teachers and
      guardians regarding the emergency contraceptive pill in Chiang Mai, Thailand.
AB  - Teachers and guardians (parents or authorized persons) are expected to
      collaborate in educating female students about emergency contraceptive pills
      (ECPs) but it is unknown whether they have similar perspectives on ECPs. This
      study aimed to compare their knowledge, attitudes, experience, and opinions
      regarding ECPs. Questionnaires were distributed to 720 female teachers and
      guardians of eight randomly selected high schools and vocational schools in
      Chiang Mai, Thailand. There were significantly more teachers who knew about the
      existence of ECPs than guardians. More guardians reported some accurate
      information regarding ECPs than did teachers. More teachers than guardians
      believed that the use of ECPs was not morally wrong. Both teachers and guardians
      had similar experience with ECP use and similar agreement in teaching female
      adolescents about ECPs. The teachers and guardians had some different opinions on
      teaching barriers. It is suggested that both teachers and guardians are suited to
      teach female adolescents about ECPs, but they need preparation in different
      aspects.

PMID- 16451427
TI  - Development and validation of the Human Activity Profile into Chinese language:
      lessons in determining equivalence.
AB  - The Human Activity Profile (HAP), and associated Dyspnea Scale, is a self-report
      instrument for assessing levels of human activity. Although it has been used in
      studies examining the levels of activity in people, it is limited to people who
      are only able to understand English. However, many countries are multicultural
      with significant numbers of people whose native language is not English. This
      study sought to demonstrate the equivalence between the Chinese and English
      versions of the HAP and Dyspnea scales. Thirty-five bilingual university students
      completed both the Chinese and English versions of each questionnaire. There was
      89% and 85% agreement between items across the HAP and Dyspnea Scale
      questionnaires, respectively. Although the psychometric evaluations suggested
      there was equivalence between the Chinese and English versions of both the HAP
      and Dyspnea Scale, lessons have been learnt regarding the different written forms
      of Chinese.

PMID- 16451428
TI  - Self-Efficacy in Infant Care Scale: development and psychometric testing.
AB  - The Self-Efficacy in Infant Care Scale (SICS) is a self-administered measure to
      assess maternal judgments about the ability to care for the baby during the first
      year of life. The SICS was initially composed of 67 items and was tested on 397
      Thai mothers with infants < 12 months old. The test demonstrated adequate
      internal consistency and test-retest reliability. Factor analysis yielded 42
      items with five dimensions of self-efficacy in infant care. With an acceptable
      model fit using confirmatory factor analysis, a final version of the SICS
      contained 40 items with four dimensions of self-efficacy in infant care:
      developmental promotion, general health care, safety, and diet. This preliminary
      test for the psychometric properties revealed that the SICS has potential uses
      for both research and clinical purposes. However, the model selected must be
      viewed as tentative; further refinement is suggested.

PMID- 16451429
TI  - Iranian staff nurses' views of their productivity and management factors
      improving and impeding it: a qualitative study.
AB  - As the biggest proportion of hospital personnel, Iranian nurses have a major role
      in providing quality care to patients. Nursing managers and nurses no longer feel
      that nurses' work is valued and they are concerned about their productivity.
      Nurses' views about productivity and management factors affecting it have been
      identified as the most important aspects affecting productivity. Thus, this study
      assesses productivity from the nurse's view. A grounded theory approach was used
      for this research. Purposive sampling and semistructured interviews were used.
      The data were analyzed using constant comparative analysis. Most participants
      felt that the qualitative nature (effectiveness) of productivity is very
      important. Also, participants indicated that management is the most important
      factor that can promote or impede their productivity. They suggested that
      managers' performance and their skill level are the factors influencing
      productivity. Effective management can improve nurses' productivity and the
      quality of care that nurses provide.

PMID- 16451430
TI  - Diagnostic practise in nursing: a critical review of the literature.
AB  - The purpose of this article is to critically review and synthesize the literature
      related to the general concepts and the process of diagnosing the client's
      condition, and the possible variables which influence diagnostic practise in
      nursing. It is suggested that statistical theories are capable of capturing the
      diagnostic process and offer an effective means to predict diagnostic decisions.
      Studies underpinned by information-processing theory argue that diagnosing a
      patient's condition follows a hypothetico-deductive model that consists of
      specific stages. Those who hold a phenomenological perspective remark that there
      is yet another form of diagnostic practise: intuitive reasoning, which plays an
      important role in diagnosing the patient's clinical condition. Other related
      studies suggest that diagnostic practise is contingent on some personal,
      psychosocial, and structural variables. Regrettably, these studies offer no
      conclusive explanation to delineate diagnostic practise in nursing. Based on the
      literature reviewed, a conceptual framework is suggested to help articulate the
      underlying structures and processes of diagnostic practise in nursing.

PMID- 16451431
TI  - Irukandji Syndrome: what nurses need to know.
AB  - Irukandji Syndrome can be frightening for the patient and make care delivery
      difficult for the nurse. Nurses' knowledge of Irukandji Syndrome has been limited
      to information provided by marine biologists, doctors, and tropical medicine
      specialists. This paper proposes to assist with the evolution of nursing
      knowledge for the care of the patient with Irukandji Syndrome. An algorithm of
      nursing management is presented that has been derived from the continuing debate
      among scientists about the etiology of signs, symptoms, and treatment rationales.
      Community safety and education surrounding Irukandji Syndrome requires concurrent
      progression of nursing knowledge and scientific inquiry.

PMID- 16451433
TI  - Risk factors for periodontitis.
AB  - This review presents a selected overview of the literature concerning risk
      factors for periodontitis. That in some individuals gingivitis develops into
      periodontitis is still a matter of extensive research. Cross-sectional studies of
      clinical and microbiological factors can be meaningful. Longitudinal studies of
      the natural history allow analysis of potential factors and conditions that may
      have an impact on the disease process. At present, several possible risk factors
      for the initiation and progression of periodontitis have been identified: age,
      gender, plaque, calculus, existing attachment loss. A consistent finding appears
      to be genetic predisposition for the development of the disease. In terms of
      microbiology, several micro-organisms have been identified. The results of the
      Java Project on natural development of Periodontal Disease clearly pinpoint
      Actinobacillus actinimycetemcomitans as being associated with the onset of
      disease. The presence of subgingival calculus was found to be associated with
      onset and dental plaque with progression of disease. Consistent with literature
      males are more susceptible to disease. The presence of pockets > or = 5 mm appear
      to be a useful tool, since it was found to be a prognostic factor for disease
      progression.

PMID- 16451434
TI  - Factors behind change in knowledge after a mass media campaign targeting
      periodontitis.
AB  - The aim of this study was to investigate changes in knowledge before and after a
      mass media campaign, in relation to social attributes, care system attributes and
      oral health aspects. The study was based on a questionnaire in a cohort design,
      sent out to 900 randomly sampled people aged 50-75 in Sweden. The response rate
      to the questionnaire before and after the campaign was 70% and 65% respectively.
      Sixty-four percent answered both questionnaires. Two questions addressed
      knowledge, while 10 questions aimed to measure social attributes, care system
      attributes and oral health aspects. Data were analysed for bivariate relations as
      to change in knowledge and social attributes, care system attributes and oral
      health aspects. Data were also analysed in multiple regression analysis with
      knowledge before, knowledge after and knowledge differences as dependent
      variables. The results showed that there were a number of independent variables
      with influence on the dependent variables. Of the social attributes, secondary
      education gave almost 10% (P < 0.001) better knowledge both before and after the
      campaign. Among care system attributes, high care utilization was related to
      knowledge both before and after the campaign. The most important factors for
      knowledge about periodontitis were education, care utilization and perceived
      importance of oral health. In conclusion, this study demonstrates that mass media
      might increase knowledge about periodontitis as a health promotion strategy.

PMID- 16451435
TI  - A laboratory study to determine the effects of universal and rotating ultrasonic
      inserts on wrist movement and scaling time efficiency of dental hygienists.
AB  - PURPOSE: The purpose of this study was to determine if differences existed in
      range of wrist movements and scaling time efficiency of dental hygienists using a
      rotating ultrasonic insert when compared with a standard universal insert.
      METHODS: A convenience sample of 32 consenting experienced dental hygienists who
      met inclusion criteria was invited to participate. Using a cross-over research
      design, the 32 participants were randomly assigned to one of the two subgroups.
      Subgroup A (n = 16) used the rotating universal ultrasonic insert on a typodont,
      rested for 15 min and the standard universal insert on a different typodont.
      Subgroup B (n = 16) used the standard universal ultrasonic insert on a typodont,
      rested for 15 min and the rotating universal ultrasonic insert on a different
      typodont. Each participant used the rotating and standard universal ultrasonic
      scaling inserts to remove 2 cm3 artificial calculus from two different typodonts
      for up to 15 min per insert. Scaling time efficiency was determined using a
      Modified Volpe-Manhold Calculus Index, measuring the amount of artificial
      calculus remaining after ultrasonic scaling. While scaling, each participant wore
      the WristSensor goniometry gloves, which determined changes in wrist movements
      (flexion and extension and ulnar and radial deviations), measured as a deviation
      from the neutral position. RESULTS: A paired t-test (P = 0.05) using 30 subjects
      with useable data, revealed no statistically significant differences between the
      two different inserts in terms of wrist movements and scaling time efficiency. A
      multivariate analysis of variance revealed no statistically significant
      differences in the percentage of time dental hygienists were in high, medium or
      low-risk posture categories while using the rotating ultrasonic insert compared
      with the standard universal insert. Based on the results of this laboratory
      study, dental hygienists using a rotating ultrasonic insert appear to experience
      no ergonomic advantage in terms of wrist postures or timesavings over a standard
      insert.

PMID- 16451436
TI  - Research defines public dental health promotion in youth.
AB  - In the Netherlands, Dental Public Health Service workers work in the healthcare
      delivery system to promote dental health. Since 1994, research has been conducted
      in Flevoland on the condition of children's teeth. This research has shaped the
      content of the dental health promotion directed at children in this region. The
      research comprises two parts: questionnaires for parents and children above the
      age of 12 and a dental examination of children aged 6 and 12 in the regional
      primary schools. The dental examination registers the health of the children's
      teeth. Sound teeth are defined as being free of visible caries and/or
      restoration. Not sound teeth show at least one case of visible caries and/or
      restoration. The research results have shown great dental differences between the
      various schools and between municipalities. The percentage of children with sound
      teeth ranges between 28 and 100 per school. Based on the final results of the
      research, an information pack will be disseminated. In the case of high-risk
      schools the dental health promotion will be conducted more intensively. The
      Dental Public Health Service workers will give information sessions to groups of
      parents and children, the dentist and the dental hygienist will provide
      individual information and prevention. At the child health clinic
      (consultatiebureau), education will be provided to parents of children ranging in
      age from 0 to 4. This combined approach has proven to be effective on a large
      majority of the children. To ensure uniform dental health promotion, information
      protocols are used in these promotion activities within Flevoland.

PMID- 16451437
TI  - The efficacy of a school-based caries preventive program: a 4-year study.
AB  - This longitudinal study aimed at testing the efficacy of a school-based caries
      preventive program, by comparing dental caries status of two groups, a study
      group (436 children) and a control group (420 children) over a period of 4 years.
      The study group received a preventive program which consisted of intensive oral
      hygiene instructions sessions, and supervised daily tooth brushing using
      fluoridated tooth paste in schools. The control group received only oral hygiene
      instructions sessions. Annual dental examination to record dental caries status,
      using Decayed Missed Filled Teeth Index (DMFT) and deft, was conducted for both
      groups over a period of 4 years. At the end of the fourth year the efficacy of
      the program was tested by comparing the DMFT and deft indices for the two groups
      using Pearson chi-square test and Cochran-Mantel-Haenzele test. The level of
      significance was set at P < 0.05. The results after 4 years showed that the
      caries status of the children in the study group was better than that of the
      control group. The difference was statistically significant (P-value 0.001). The
      estimates of relative risk values also showed that children in the control group
      are 3.1 and 6.4 times at higher risk of having dental caries than those in the
      study group for age group 12 and 6 respectively. This study proves that
      supervised daily tooth brushing using fluoridated toothpaste is successful in
      controlling dental caries in children.

PMID- 16451438
TI  - Inter-individual variation in the plaque formation rate of young individuals.
AB  - OBJECTIVES: The aim of the present study was to describe the inter-individual
      variation in the plaque formation rate of 38 young adults. METHODS: The plaque
      formation rate was estimated by employing a quantitative plaque percent index (P%
      index). A substantial inter-individual variation in the plaque formation rate was
      observed. The possible contributions of stimulated salivary flow rate, buffer
      capacity, diet and smoking to the variation in plaque formation were estimated by
      regression analysis. RESULTS: The control variables explained only 2.5% of the
      variance in the plaque formation rate. Neither associations nor the total model
      were significant. The present method of measuring plaque presented as a simple
      and time-effective procedure. CONCLUSIONS: It is suggested that the observed
      variation in the plague formation rate between the young individuals can be
      regarded as a biological function which is possibly an inherent individual
      characteristic. Studies with larger sample sizes are required to confirm the
      findings of the present study.

PMID- 16451439
TI  - Periodontal response to all-ceramic crowns (IPS Empress) in general practice.
AB  - OBJECTIVE: The purpose of this study was to investigate the periodontal response
      to the presence of all-ceramic crowns (IPS Empress) in general practice patients.
      METHODS: The convenience sample included 82 IPS Empress crowns placed in 64
      patients. These crowns had been in place for an average of 16.27 (SD 9.26) months
      and ranged from 6.2 to 48.87 months at the time of clinical examination.
      Periodontal health status (as determined by dental plaque, gingival health
      status, periodontal pockets) was assessed around all crowned teeth and around
      matched contralateral teeth by one calibrated examiner. Periodontal indices
      utilized included the Plaque Index (PI), Gingival Index (GI) and pocket depth
      (PD) with calibrated probes graduated in millimetres. Plaque, gingival and PD
      values for crowned teeth were compared with those for control teeth using
      Wilcoxon signed-rank test for each clinical parameters. Chi-square was used to
      test the significance of the difference in their distribution between crowns and
      control teeth. RESULTS: Statistically, PI (0.35), GI (0.41) and mean PD scores
      (1.42) of IPS Empress crowned teeth compared less favourably with scores of the
      control teeth (0.27, 0.23 and 0.86 respectively). CONCLUSION: Teeth with IPS
      Empress crowns had poorer periodontal health and more clinically evident plaque
      than uncrowned teeth.

PMID- 16451440
TI  - Integration of oral health into primary health care: the role of dental
      hygienists and the WHO stewardship.
AB  - Interest in addressing the unmet oral health needs of the citizens of the world
      has manifested itself, lately, in noteworthy expressions of commitment. Oral
      health is integrated with general health and support for community programmes
      offering 'essential oral health' within primary health care (PHC) is increasing.
      The WHO Global Goals for Oral Health 2020 has assumed a more directed public
      health orientation, and the Global Oral Health Programme has its focus on
      modifiable oral risk behaviours. Last, but not the least, opportunities are being
      created, under the 'stewardship' of the World Health Organization (WHO), for the
      expansion of oral disease prevention and health promotion knowledge and practices
      in communities. A review of the literature on community-oriented oral health
      primary care reveals one dominant and disease-oriented practice model with dental
      practitioners being the principal and exclusive actors. One alternative to this
      biomedical model of care that may be better suited to translate health promotion
      principles into action at community levels is the practice that involves
      hygienists serving as primary oral health care providers. The WHO 'stewardship'
      should include the support of dental hygiene practice within PHC, many
      legislative restrictions and regulatory barriers would be relaxed, thus enabling
      dental hygienists to respond to the WHO's call for community-based demonstration
      projects. With their focus on preventive oral care, hygienists are 'best poised'
      to help accelerate the integration of oral health with primary care, particularly
      in the light of the compelling evidence confirming the cost-effectiveness of the
      care delivered by intermediate providers.

PMID- 16451441
TI  - The oral healthcare professional's role in the assessment and treatment of eating
      disorders.

PMID- 16451443
TI  - Is your knowledge up-to-date?

PMID- 16451446
TI  - Seniors' attitudes: oral health and quality of life.
AB  - The objective of this study was to determine what impact, if any, oral health was
      having on the quality of life for selected seniors in Prince Edward Island,
      Canada. The attitudes of seniors towards oral health and its relationship to
      quality of life is important to define. This self-reported assessment provides
      information on this particular relationship. The research design was a random
      cluster sampling that covered all geographical areas of Prince Edward Island. It
      represented the cultural diversity within these geographical areas. The survey
      instrument selected was the Subjective Oral Health Indicators' Status, a
      validated survey instrument. This particular instrument addressed all the issues
      raised in the objectives. Data were analysed using Pearson's correlation with age
      and number of teeth present. The independent t-test was used to identify
      differences in responses by gender. Results of the survey showed identification
      of individual indicators that were having an impact on quality of life. Gender
      differences in responses were identified in four of the eight subject areas. The
      level of worry/concern was inconclusive because of the high non-response rate to
      the last question. Non-response rates increased with each topic in the
      questionnaire. More research is needed to identify clinical needs of seniors on
      Prince Edward Island. Qualitative study to determine attitudes and beliefs could
      provide groundwork for future programme design.

PMID- 16451447
TI  - Attitudes to and perceptions of oral health and oral care among community
      dwelling elderly residents of Stockholm, Sweden: an interview study.
AB  - The aim of this study was to document perceptions of oral health of community
      dwelling elderly people and how it had been affected through life. Twelve
      individuals (mean age 78.2 years) were gradually recruited to an interview study.
      The interviews were conducted as conversations, and the topics in a guide model
      were introduced only if they did not arise spontaneously. The interviews lasted
      60-90 min and were tape-recorded and transcribed verbatim and analysed by the
      phenomenological-hermeneutic method. The interviews dealt with perceptions of
      growing old, life style, general health, former dental experiences, dental care
      in adult life, current oral health, general medical care, dental care, oral
      hygiene, dental hygienist care and the level of participation in treatment
      decisions. The interviewees were generally satisfied with their present oral
      health and often referred to their parents' oral problems as deterrents. Dental
      experiences from childhood, in association with the welfare state and personal
      financial security, were factors which influenced attitudes and perceptions of
      oral health and oral care. Although dental care was regarded as very expensive,
      it had been given priority over other expenses in adult life. The results confirm
      that the dental hygienist must take into account the importance of oral health to
      well being in old age and be aware that in elderly people, perception of personal
      oral health is multifactorial, influenced by life-long experience.

PMID- 16451449
TI  - Surgical magnification in dental hygiene practice.
AB  - The potential for improving the occupational health of dental clinicians has
      expanded as increasingly sophisticated equipment enters the marketplace, yet
      there has been little improvement to the ergonomics with which dental hygienists
      operate. The use of surgical magnification has great potential to increase the
      quality of dental hygiene clinical care and to support the musculoskeletal health
      of dental hygienists. Although the research evidence to support a relationship
      between the use of surgical magnification and increased quality of dental hygiene
      care is extrapolated from parallel studies in dentistry, specific dental hygiene
      studies suggest that the integration of surgical magnification would be helpful
      in reducing the incidence of musculoskeletal symptoms experienced by dental
      hygienists. This is not to suggest that the integration of surgical magnification
      is a panacea for the musculoskeletal problems experienced by dental hygienists.
      In fact, improperly selected or adjusted surgical magnification systems can
      promote positions that place clinicians at increased risk for such problems.
      Clinicians must first determine the optimal working position that supports their
      musculoskeletal health and then select magnification systems that will support
      that position. The working distance, depth of field and optical declination angle
      of the chosen system must correspond to the musculoskeletal needs of the
      clinician.

PMID- 16451448
TI  - Oral manifestations in selective IgA deficiency.
AB  - Selective immunoglobulin A (IgA) deficiency is the most common of the primary
      immunodeficiencies with a frequency of 1/300-1/3000, depending on the screened
      population. As secretory IgA (SIgA) has a protective role in mucosal surfaces
      from invasion of microorganisms, it is thought that IgA-deficient subjects are
      susceptible to periodontal diseases and oral manifestations. Previous studies
      show contradictory results, concerning the involvement of the individuals'
      periodontium with IgA deficiency. The aim of this study was to investigate and
      compare the oral manifestations in IgA-deficient subjects with controls. Eleven
      selective IgA-deficient subjects aged 3-18 years with serum IgA levels <10 mg dl(
      1) and 11 age-sex-matched healthy children as the controls entered the study.
      Oral mucosal investigation, dental caries, plaque accumulation and periodontal
      status were assessed. Serum immunoglobulin levels were measured by single radial
      immunodiffusion (SRID) method. Saliva immunoglobulins and secretory component
      levels were measured by enzyme linked immunosorbent assay (ELISA) methods. IgA
      deficient patients had serum and saliva IgA levels less than 10 mg dl(-1) and 10
      microg ml(-1), respectively, but other serum immunoglobulin levels were normal
      and saliva immunoglobulin M (IgM) levels were increased, compared with controls.
      There were no significant differences in oral manifestations between IgA
      deficient subjects and controls, which may be a result of compensatory increase
      of saliva IgM or other non-immunological defence factors in saliva. Thus, it is
      not necessary to evaluate IgA and SIgA in all the patients with oral and dental
      lesions and it is thought that it is better to investigate other factors.

PMID- 16451450
TI  - The collaborative practice of dental hygiene.
AB  - This paper discusses the collaborative practice of dental hygiene, primarily
      using examples from California and New Mexico. Several advantages are discussed,
      including an increased access to all populations and more respect for the field.
      The earliest roles of a dental hygienist reflect common components of a
      collaborative practice. Responsibilities of dental hygienists today as educators
      and preventive dental providers are also tied to this type of practice.
      Currently, few states in the USA allow such practices; however, benefits are
      discussed and the positive effects noted. Opposition to these practices exists,
      although the concerns have not been proven accurate. Collaborative dental hygiene
      practices are shown to be a positive avenue through which the population can gain
      access to noted provider shortages, as well as a rewarding option for the field
      of dental hygiene.

PMID- 16451451
TI  - Power toothbrushes: a critical review.
AB  - Although the first toothbrush is thought to have been used in about 1000 ad,
      tooth brushing in America did not gain popularity until after 1945. The
      introduction of the powered toothbrush in 1960 has led to a large number of
      studies comparing the safety and efficacy of powered toothbrushes to manual
      toothbrushes. There is a general agreement that powered toothbrushes are as safe
      as manual toothbrushes; however, studies show significantly differing conclusions
      regarding the efficacy of power toothbrushes for the removal of plaque. The
      recent amendment of the Cochrane report on this subject concluded that the only
      type of powered toothbrush that removes more plaque than a manual toothbrush is
      one with rotational oscillation movement. Their conclusion was based on the
      review of 29 published studies, conducted between 1964 and 2001, with a total of
      2547 participants. All these studies used similar research design criteria. The
      Cochrane conclusion is in agreement with a 1996 study carried out in the
      Netherlands. Many of the conflicting study conclusions, to date, on powered
      toothbrushes, are the result of using differing study design criteria. While the
      dental profession desires evidence-based research, it is clear that dental
      schools will need to increase the level of attention in their curriculum to
      address disciplined techniques for research design in order to reconcile the
      large variances in reported research results.

PMID- 16451459
TI  - Is your knowledge up-to-date? Periodontal abscess.

PMID- 16451463
TI  - Smoking, periodontal disease and the role of the dental profession.
AB  - Epidemiological investigations support a firm relationship between smoking and
      periodontal disease. The likely benefits of smoking cessation programmes are
      considerable for periodontal disease, cancers and nearly all chronic systemic
      diseases. The mechanisms by which smoking may influence the development and
      progression of periodontal disease are as yet unclear, but may include changes in
      the vasculature, the immune and inflammatory systems, tissue oxygenation and the
      healing processes. Unfortunately, although dental professionals have more
      opportunities to encourage smokers to quit (most people visit their dentist more
      frequently than their doctor), dentists claim that they are not well informed on
      this subject. The purpose of this review is to describe the evidence for a link
      between smoking and periodontal disease, the possible pathology induced by
      smoking on the periodontal tissues and its impact on therapy, and to outline the
      smoking cessation techniques that are currently available.

PMID- 16451464
TI  - A cross-sectional study of buccal cervical sensitivity in UK general dental
      practice and a summary review of prevalence studies.
AB  - AIM: The initial aim of this study was to establish the prevalence of dentine
      hypersensitivity (DH) in a cross-sectional study of patients visiting general
      dental practitioners in the UK over a period of one calendar month. METHODS:
      Eighteen dental practitioners examined 5,477 patients over a period of one
      calendar month, and patients who were diagnosed with DH were questioned further
      about their occupation and smoking habits. The amount of buccal gingival
      recession associated with the sensitive teeth was also recorded, as was the
      presence of periodontal disease. RESULTS: One hundred and fifty-two patients were
      diagnosed as having DH, giving a prevalence figure of 2.8%. The commonest teeth
      affected were the first molars and premolars, and the commonest initiating factor
      was cold drinks. A tendency for a greater number of DH teeth was also found for
      patients with periodontal disease who also smoked. There was also a tendency for
      the patients with DH teeth to come from higher social groups. CONCLUSION: At the
      time of conducting this study, the European Federation of Periodontology had not
      recommended that sensitive teeth associated with periodontal disease and
      treatment be termed root sensitivity (RS). The title of this paper was therefore
      chosen to reflect this decision, and the data represent teeth both within and
      between subjects with DH and RS.

PMID- 16451465
TI  - Oral health problems in elderly rehabilitation patients.
AB  - A combination of poor oral hygiene and dry mouth may be hazardous to the oral
      health status. However, systematic assessments in order to detect oral health
      problems are seldom performed in the nursing care of the elderly. The aims of
      this study were to investigate the occurrence of oral health problems measured
      using the Revised Oral Assessment Guide (ROAG) and to analyse associations
      between oral health problems and age, gender, living conditions, cohabitation,
      reason for admission, number of drugs, and functional and nutritional status. One
      registered nurse performed oral health assessments using ROAG in 161 newly
      admitted elderly patients in rehabilitation care. Oral health problems were found
      in 71% of the patients. Thirty per cent of these patients had between four and
      eight problems. Low saliva flow and problems related to lips were the most
      frequent oral health problems. Problems in oral health status were significantly
      associated with presence of respiratory diseases (problems with gums, lips,
      alterations on the tongue and mucous membranes), living in special accommodation
      (low saliva flow, problems with teeth/dentures and alterations on the tongue),
      being undernourished (alterations on the tongue and low saliva flow) and being a
      woman (low saliva flow). The highest Odds ratio (OR) was found in problems with
      gums in relation with prevalence of respiratory diseases (OR 8.9; confidence
      interval (CI) 2.8-27.8; P < 0.0005). This study indicates the importance of
      standardised oral health assessments in order to detect oral health problems
      which can otherwise be hidden when the patients are admitted to the hospital
      ward.

PMID- 16451466
TI  - Oral health knowledge and dental health practices among schoolchildren in Jerash
      district/Jordan.
AB  - OBJECTIVE: This study aims at determining the oral health awareness level, the
      patterns of dental health practices and their potential relationship with certain
      socio-demographic factors, including gender (sex), mother's education and the
      socio-economic status of the family, among 14-15-year-old schoolchildren in
      Jerash Governorate, Northern Jordan. PARTICIPANTS AND METHOD: Cross-sectional
      survey including 1362 public schoolchildren, who completed a self-administered
      structured questionnaire. RESULTS: Overall, the level of oral health knowledge
      among the surveyed children was low. Of the 1362 schoolchildren included in this
      survey, only 18 and 17% did know the meaning of plaque and what plaque can cause,
      respectively. Female performance was significantly better than male performance
      on two of the six knowledge questions (P < 0.01). While 17% of children have
      never been to the dentist, there are 10% only who visit the dentist on regular
      basis. The majority (56%) of these pupils said they visit the dentist when there
      is a serious dental or oral health problem. Fear of the dentist and difficulty in
      obtaining an appointment with the dentist were the causes of irregular visit to
      the dental clinic in 28 and 19% of the cases, respectively. CONCLUSION: Results
      of this study prove that oral health awareness level among public schoolchildren
      in Jordan is still poor and needs to be improved. Based upon these findings, the
      establishment of a long-term school-based oral health education programme in
      Jordan is highly recommended.

PMID- 16451468
TI  - Life-saving medical advances: help for a healthier 2004.

PMID- 16451467
TI  - Establishing dental hygiene education in Germany: current facts and future
      perspectives.
AB  - As there is a marked need to increase the number of dental hygienists (DHs)
      working in German dental practices, efforts are being made to establish dental
      hygiene education in accordance with international standards. However, as current
      German legislation does not envisage a perennial full-time training programme,
      dental hygiene education may currently be provided within a modular concept only.
      The basic qualification for enrollment in a modular hygienist training programme
      of this kind is accredited vocational training as a dental assistant (DA),
      followed by board-certified continuing education as an oral prophylaxis
      assistant. Thus, the current system of advanced training for qualification as a
      DH is subject to at least 6 years' work experience in the field of dentistry. A
      950-h full-time advanced training course, meeting all the requirements of this
      concept, was established by the Westphalia-Lippe Dental Association in
      cooperation with the University of Munster. The curriculum underlying this
      programme was outlined considering the recommendations for dental hygiene
      education issued by the European Federation of Periodontology, although reduced
      in standards to comply with current German legislation. In addition, the
      recommendations for American Dental Hygiene education by the American Dental
      Association were used as a guide for programme development. The contents and
      implementation of the Munster Dental Hygienist Curriculum may allow the
      professional competence generated during practical work experience to be linked
      with international requirements of dental hygiene education.

PMID- 16451469
TI  - Website update.

PMID- 16451470
TI  - Tongue piercing: part I.

PMID- 16451473
TI  - Suppression of overt gingival inflammation in tobacco smokers - clinical and
      mechanistic considerations.
AB  - Gingivitis is a reversible inflammatory disease of the periodontal tissues.
      Periodontitis, in addition, involves destruction of the supporting structures of
      teeth. Diagnoses of gingivitis and periodontitis are predominantly dependent on
      clinical measurements of key inflammatory indices. Smokers are more susceptible
      to developing periodontal diseases, yet smoking masks overt signs of
      inflammation, presenting dental professionals with a clinical conundrum. We
      review the evidence that tobacco smoke may (i) cause acute periodontal
      vasoconstriction, (ii) inhibit periodontal angiogenesis in response to
      inflammatory stimuli, and/or (iii) suppress the production of pro-inflammatory
      mediators. It is clear that the mechanisms by which cigarette smoking dampens the
      periodontal inflammatory response are not yet fully understood. Further research
      into inflammatory suppression is warranted and should point to improved methods
      of diagnosis, not only in smokers, but also in non-smokers.

PMID- 16451474
TI  - A review of common herbs and potential interactions.

PMID- 16451475
TI  - Chlorhexidine with an Anti Discoloration System. A comparative study.
AB  - Correct oral hygiene is believed to be the basis of primary and secondary
      prevention. Sometimes, using a toothbrush or other mechanical instruments for
      oral hygiene may be difficult and it may become necessary to use an antiseptic.
      Chlorhexidine is an essential component in many available preparations on sale,
      because of its marked antiseptic qualities. One of the most frequent side-effects
      is the appearance of stains on the teeth and mucous membranes, which particularly
      disturbs the patient. A new mouthwash containing chlorhexidine has recently
      become available, besides maintaining its antiseptic qualities, also avoids the
      side-effect of staining. OBJECTIVES: The aim of this study was to check the
      capacity of the new mouthwash, which contains chlorhexidine and Anti
      Discoloration System (ADS), not only to prevent plaque formation like the other
      mouthwashes containing chlorhexidine but also to avoid staining that is one of
      the most frequent side-effects. STUDY DESIGN: The comparative study was carried
      out on a sample of 15 patients treated with two mouthwashes both containing 0.2%
      chlorhexidine, but different in that the first does not contain ADS, which is
      instead present in the second, a new product. The results obtained show that in
      the 15 patients treated, there is no statistically significant difference in the
      ability of the mouthwash to prevent bacterial plaque, however evidence of the
      stain was much less with the new mouthwash.

PMID- 16451476
TI  - Dental hygiene in Slovakia.
AB  - This article reports on the development of the dental hygiene profession in
      Slovakia from a global perspective. The aim is to inform about current
      developments and to examine, how access to qualified dental hygiene care might be
      improved and how professional challenges might be met. For an international study
      on dental hygiene, secondary source data were obtained from members of the House
      of Delegates of the International Federation of Dental Hygienists (IFDH) or by
      fax and e-mail from experts involved in the national professional and educational
      organization of dental hygiene in non-IFDH member countries, such as Slovakia.
      Responses were followed-up by interviews, e-mail correspondence, visits to
      international universities, and a review of supporting studies and reference
      literature. Results show that the introduction of dental hygiene in Slovakia in
      1992 was inspired by the delivery of preventive care in Switzerland. Initiating
      local dentists and dental hygienists strive to attain a high educational level,
      equitable to that of countries in which dental hygiene has an established
      tradition of high quality care. Low access to qualified dental hygiene care may
      be a result of insufficient funding for preventive services, social and cultural
      lack of awareness of the benefits of preventive care, and of limitations inherent
      in the legal constraints preventing unsupervised dental hygiene practice. These
      may be a result of gender politics affecting a female-dominated profession and of
      a perception that dental hygiene is auxiliary to dental care. International
      comparison show that of all Eastern European countries, the dental hygiene
      profession appears most advanced in Slovakia. This is expressed in high evidence
      based academic goals, in extensive work with international consultants from the
      Netherlands and Switzerland, in annual congresses of high professional quality,
      and in the establishment of a profession, which has not been introduced in all
      Western EU countries.

PMID- 16451477
TI  - Assessment of periodontal knowledge and periodontal status of an adult population
      in Jordan.
AB  - The aim of this study was to assess periodontal knowledge and periodontal status
      in 20-60-year-old adult population in northern Jordan. A convenient sample
      consisting of 722 adults was included in this study. A questionnaire
      incorporating items related to socio-demographic and periodontal knowledge
      questions was completed before clinical examination, using the Community
      Periodontal Index of Treatment Needs (CPITN). The results showed that the
      proportions of subjects who reported bleeding gums, gums' irritation, rough tooth
      surface and gum disease decreased steadily with age, there is an evident linear
      trend with high statistical significant difference among various age groups (P <
      0.001). Furthermore, the proportions of subjects who answered correctly the
      periodontal knowledge questions related to plaque definition and its role in
      disease aetiology and prevention, decreased with age, with a high significant
      difference for all knowledge questions (P < 0.001). The prevalence of subjects
      with healthy periodontium (score 0) decreased with age, being 41.1% among 20-29
      year-old group and 11.1% in 50-60-year-old group. Similar trend was seen for
      bleeding on probing (score 1) whilst calculus deposit (score 2) was the major
      problem in all age groups over 29 years. The prevalence of periodontal pockets
      was relatively low, with a range of 4.5-18.6% for shallow pockets (score 3) and
      2.9-11.1% for deep pockets in younger and older age groups, respectively. Younger
      age group had more healthy sextants than older age groups. In addition, sextants
      with bleeding on probing were highest in 20-29-year-old age group (1.8) compared
      with that in 50-60-year-old age group (0.60) whilst those with calculus deposits
      varied slightly among different age groups (1.50-1.65). Sextants affected by
      shallow or deep pockets increased steadily with age. Such a finding was also
      noted in excluded sextants, with an increase from 0.15 at 20-29 year-old group to
      0.94 at the age of 50-60 years. It is concluded that health knowledge and status
      related to periodontal disease is still poor in northern Jordan. Therefore,
      dental health education provision is necessary to improve oral health knowledge
      and conditions among population in general and among older population in
      particular.

PMID- 16451478
TI  - Secretion rate and buffer capacity of whole saliva depend on the weight of the
      mechanical stimulus.

PMID- 16451479
TI  - C-reactive protein, cardiovascular disease, and periodontal disease.

PMID- 16451484
TI  - Website update.

PMID- 16451485
TI  - Tongue piercing: part II.

PMID- 16451487
TI  - Comment from the DDHV in response to your article: 'Establishing dental hygiene
      education in Germany: current facts and future perspectives'.

PMID- 16451489
TI  - Evidence-based practice and the professionalization of dental hygiene.
AB  - The application of knowledge is fundamental to human problem solving. In health
      disciplines, knowledge utilization commonly manifests through evidence-based
      decision making in practice. The purpose of this paper is to explore the
      development of the evidence-based practice (EBP) movement in health professions
      in general, and dental hygiene in particular, and to examine its relationship to
      the professionalization agenda of dental hygiene in Canada. EBP means integrating
      practitioner expertise with the best available external evidence from research.
      Proponents of EBP believe that it holds promise for reducing a research-practice
      gap by encouraging clinicians to seek current research results. Both the Canadian
      and American Dental Hygienists Associations support practice based on current
      research evidence, yet recent studies show variation in practice.
      Professionalization refers to the developmental stages through which an organized
      occupation passes as it develops traits that characterize it as a profession. The
      status conferred by professionalization privileges a group to make and monitor
      its own decisions relative to practice. Dental hygiene's success in acquiring
      attributes of a profession suggests that transformation to a profession is
      occurring. This paper compares the assumptions and challenges of both movements,
      and argues the need for a principal focus on the development of a culture of
      evidence-based dental hygiene practice.

PMID- 16451490
TI  - Teledentistry in the United States: a new horizon of dental care.
AB  - Teledentistry has been developing since 1994 as a means to allow dental
      professionals to communicate with one another over long distances. It allows
      collaboration by multiple practitioners regarding a patient and the necessary
      treatment for this patient. Teledentistry can be greatly utilized with rural
      communities or those of underserved populations. It would increase the
      accessibility of specialists, besides decreasing time and cost associated with
      specialty consultations. Real-time videoconferencing and store and forward
      techniques are the mostly commonly used methodologies for teledentistry.
      Teledentistry will become more widely seen and utilized by the increase in
      digital media found in dental practices.

PMID- 16451491
TI  - Dental hygiene in Australia: a global perspective.
AB  - AIM: This article reports on the practice of dental hygiene in Australia from a
      global perspective. The aim is to examine how access to qualified dental hygiene
      care could be improved and how current professional challenges might be met.
      METHOD: Secondary source data were obtained from a survey questionnaire presented
      to members of the House of Delegates of the IFDH or by fax and e-mail to experts
      involved in the national professional and educational organization of dental
      hygiene in non-IFDH member countries. Responses were followed-up by interviews, e
      mail correspondence, visits to international universities, and a review of
      supporting studies and reference literature. RESULTS: The introduction of dental
      hygiene in Australia was inspired by the delivery of preventive care in Great
      Britain. Today dental hygiene is a paramedical profession, generally studied at
      institutions of higher education. Study duration is 2 (diploma and associate
      degree programmes) and 3 years (Bachelor of Oral Health Programs). A recent trend
      to combine dental therapy and dental hygiene education poses the challenge to
      maintain a stand-alone degree in dental hygiene as it is practiced worldwide. Low
      access to qualified dental hygiene care may be a result of insufficient funding
      for preventive services, social and cultural lack of awareness of the benefits of
      preventive care, and of limitations inherent in the legal constraints preventing
      unsupervised dental hygiene practice. These may be a result of gender politics
      affecting a female dominated profession and of a perception that dental hygiene
      is auxiliary to dental care. Changes are expected to reflect the global trend
      towards a decrease in supervision and towards higher education. An example of
      innovative practice of public health is the involvement of dental hygienists in
      the educational process of aboriginal health workers in order to promote access
      to oral health education for indigenous populations.

PMID- 16451492
TI  - Knowledge on gingivitis and oral hygiene practices among secondary school
      adolescents in rural and urban Morogoro, Tanzania.
AB  - OBJECTIVES: To assess and compare knowledge on gingivitis and oral hygiene
      practices among rural and urban secondary school students. DESIGN: A cross
      section descriptive study involving secondary school students aged between 13 and
      17 years in Morogoro rural and urban districts. METHODS: Questionnaire was used
      to collect information about knowledge on causes, signs, symptoms, complications,
      treatment modalities and prevention of gingivitis, as well as on oral hygiene
      practices. RESULTS: A total of 196 students participated in this study, of which
      58.7% were females, and 52% were from urban schools. The responses were graded
      into three criteria namely 'lack of knowledge', 'partial knowledge' and 'total or
      full knowledge'. There was a partial knowledge about gingivitis and full
      knowledge of the basic oral hygiene measures among secondary school teenagers.
      The difference between rural and urban residence on the level of understanding
      was statistically significant in relation to tooth brushing practices (P =
      0.0088), necessity of using toothpaste (P = 0.0204), reasons for using toothpaste
      (P = 0.0057), signs and symptoms of gingivitis (P = 0.0261) and treatment of
      gingivitis (P = 0.0106). However, there were no statistically significant
      differences in distribution of study participants, understanding of tooth
      brushing practices, reasons for tooth brushing, causes, prevention and
      complications of gingivitis. CONCLUSION: Secondary school teenagers have partial
      knowledge about gingivitis and a good knowledge of the basic oral hygiene
      measures necessary to maintain proper oral health. A small difference on
      knowledge in specific areas was noted among rural and urban respondents.

PMID- 16451493
TI  - Dental hygiene education in Japan: present status and future directions.
AB  - The aim of this report is to provide basic information about the historical
      development, current status and future needs of education and training of dental
      hygienists in Japan. The first formal training of dental hygienists in Japan
      started at Tokyo in 1949. Restructure and modification of the dental hygiene
      education system has been reiterated over the years in order to satisfy the needs
      of the constantly changing society. Although previously only vocational training
      was provided for dental hygienists, higher-level education has been conducted.
      The present legislation of dental hygiene has gone through a complicated process.
      The student should take the dental hygienist licensing examination which is held
      once a year by the National Board organized by the Ministry of Health, Labour and
      Welfare. Currently there are 136 dental hygiene schools and the total enrolment
      is about 7000. The duration of dental hygiene education course has been prolonged
      from 2 to 3 years since 2001. In 2004, the 4-year course started. The 2-year
      dental hygiene education program is expected to be replaced with the 3- and 4
      year courses by 2010. The dental hygiene education system in Japan will be
      improved in many ways as dental hygienists are expected to participate in health
      promotion and preventive care, and to gain knowledge of the economics and
      organization of health care in relation to oral hygiene.

PMID- 16451494
TI  - Oral bacteria and clinical variables in dependent individuals at a special
      facility.
AB  - The oral health of dependent residents at special facilities has often been
      reported as being poor, but it is difficult to relate oral health to general
      health and define the need for oral health care. Microbiological analyses of the
      oral flora have been suggested as a suitable method for evaluating oral health in
      this group of patients. A study was performed at a nursing facility where 33
      individuals participated. The aim was to describe their oral flora in relation to
      other health variables and to classify the residents on different risk levels. An
      oral examination of the residents was made at the facility, together with a 3-day
      food record and an oral microbiological analysis. The analysis classified the
      residents in different categories according to both acid-producing bacteria and
      the flora correlated with a reduction in general health. The categories were
      based on previous studies conducted at the Department of Microbiology (Faculty of
      Odontology in Goteborg). The present study revealed that the level for acid
      producing bacteria was high in 12 individuals and the micriobial level according
      to decreased general health was high in seven individuals. A high level of acid
      producing bacteria was related to functional impairment, which was in turn
      related to nutritional problems and help with oral hygiene. The microbial level
      according to the reduction in general health did not significantly correlate with
      other variables.

PMID- 16451495
TI  - Women and heart disease: new AHA guidelines. What oral health care professionals
      need to know.

PMID- 16451496
TI  - Is your knowledge up-to-date?

PMID- 16451497
TI  - Website update.

PMID- 16451500
TI  - How to select the right mouthrinses in periodontal prevention and therapy. Part
      II. Clinical use and recommendations.
AB  - Based on scientific proof, only few mouthrinse solutions can be recommended.
      However, it is impossible to construct an extended table that would provide
      precise recommendations or advices for mouthrinse utilisation related to any
      possible discomfort or diseases. Only reliable information on the drugs available
      against periodontal disease can be offered to the therapist. By evaluation of her
      or his individual experiences, she or he has to judge all the armamentarium she
      or he possesses to react in the best possible way in each specific situation.

PMID- 16451501
TI  - The effects of gender disparities on dental hygiene education and practice in
      Europe.
AB  - In Europe, over 96.5% of dental hygienists are women. The objective of this
      report was to examine the impact of gender role stereotyping on the image of the
      dental hygiene profession and on disparities in educational attainment and work
      regulations within Europe. Data pertaining to regulated or non-regulated dental
      hygiene practice in 22 European countries were analysed according to possible
      gender impact on access to education and on the structure of the delivery of
      care. It was examined whether there is a correlation between national differences
      found in the dental hygiene profession and gender related disparities found in
      other work-related areas. Results show that the gender bias in the dental hygiene
      profession has an effect on equal access to education, and on equal occupational
      opportunities for dental hygienists within the European Union (EU) and beyond. In
      northern Europe, higher educational attainment in the field of dental hygiene,
      more extensive professional responsibilities and greater opportunities for self
      employment in autonomous practice tend to correlate with greater equality in the
      work force. In eastern Europe, lower educational and professional opportunities
      in dental hygiene correlate with greater gender disparities found in other work
      related areas. In some western European countries, the profession has not been
      implemented because of the political impact of organised dentistry, which expects
      financial loss from autonomous dental hygiene practice. In order to fulfil
      mandates of the EU, initiatives must be taken to remove the gender bias in the
      delivery of preventive care and to promote equal access to educational attainment
      and to professional development in the whole of Europe for those who choose to do
      so.

PMID- 16451502
TI  - Social relations and breath odour.
AB  - In this retrospective qualitative study, the researcher reviewed 55 client
      records of The Breath Odour Clinic. The purpose was to determine if individuals
      attended a clinic specialised in treating oral malodour for medical or social
      reasons. The study focused on the psychosocial and breath odour history. Clients
      had agreed to the use of information for research purposes. Society uses odour as
      a means to define and interact with the world. The olfactory, smelling experience
      is intimate, emotionally charged and connects us with the world. It follows that
      the smell from mouth breath odour can connect or disconnect a person from their
      social environment and intimate relationships. How one experiences one's own body
      is very personal and private but also very public. Breath odour is public as it
      occurs within a social and cultural context and personal as it affects one's body
      image and self-confidence. Body image, self-image and social relations mesh,
      interact and impact upon each other. Breath odour is a dynamic and interactive
      aspect of the self-image. In addition, breath odour may be value-coded as 'bad'.
      In 75% of the cases reviewed, decreased self-confidence and insecurity in social
      and intimate relations led clients to seek treatment at the specialised breath
      odour clinic. Their doctor, dental hygienist or dentist had treated medical and
      oral conditions but not resolved their breath odour problem. When a person
      perceives a constant bad breath problem, she/he uses defence techniques, and may
      avoid social situations and social relations. This affects a person's well-being.

PMID- 16451503
TI  - Quality assurance and dental hygiene.
AB  - Dental hygiene in Canada has experienced significant growth. It has shifted from
      an emerging occupation to a regulated health profession in several jurisdictions.
      Many achievements may be attributed to this growth, including self-regulation and
      a national code of ethics. However, the majority of Canadian dental hygienists
      are relying on traditional, outdated and ineffective quality assurance
      mechanisms, such as mandatory continuing education requirements. In the interests
      of public protection, dental hygiene needs to ensure that the quality assurance
      activities required from its members are effective, valid and reliable. Quality
      assurance in health care continues to undergo modifications that better reflect
      the public's need for competent, ethical, safe and appropriate health care.
      Dental hygienists and dental hygiene regulatory bodies are challenged to find
      valid, reliable and effective methods of quality assurance. This paper discusses
      some of the developments in quality assurance in health care as well as some of
      the key and significant achievements of dental hygiene in Canada. The use of
      quality assurance mechanisms currently used in dental hygiene in Canada is also
      discussed. The paper concludes with a discussion on the potential barriers and
      issues that the profession may face when attempting to incorporate suitable
      quality assurance activities into daily dental hygiene practice.

PMID- 16451504
TI  - The Dental Hygiene Program in Portugal.
AB  - The Dental Hygiene Program is a fairly recent addition in the field of the health
      professions in Portugal. In the past 19 years, the programme has developed
      community activities alongside with clinical work. This programme provides an
      education that is responsive, scientific and professional, in a learning
      environment that is dynamic, student-centred and that encourages collaboration
      between students and faculty. The community activities play a major role in the
      curricula of the programme and allow the students to develop skills in working
      with a wide range of population groups and to attend to their specific needs.
      Dental hygienists are integrated in health teams and work under the supervision
      of a physician or a dentist. Among other responsibilities, the following
      functions are part of the scope of the profession: to participate in health
      education programmes and sensitise the population to the prevention of dental
      diseases, to participate in the planning, implementation, and evaluation of the
      public health programmes and to perform clinical treatment for prevention and
      control of gingivitis, periodontitis, and dental caries. An overview of the
      activities developed in the year 2002 and future perspectives are presented in
      this article.

PMID- 16451506
TI  - New research paradigm.
AB  - Scientists are looking at a variety of ways to prevent disease and help insure
      wellness across the lifespan. Health and disease are linked to human behavior,
      environment, and biology. Biological influences are many, including a person's
      sex. Age-old infectious diseases continue to warrant out attention, whether they
      are acute or chronic. Changing models of disease are focusing on quality of life
      issues, taking into account the physiological and social influences that affect
      one's life from cradle to grave. This article reviews recent discoveries in the
      area of antibiotics, premedication, genetics, obesity, tongue piercing, and
      tongue splitting. As oral health care professionals, dental hygienists should be
      aware of the latest trends in research, and models of disease prevention and
      maintenance of wellness.

PMID- 16451505
TI  - Evaluation of motivation methods used to obtain appropriate oral hygiene levels
      in schoolchildren.
AB  - The aim of the present study is to assess the behaviour of different motivation
      methods on levels of oral hygiene among schoolchildren aged from 7 to 9 years in
      Araraquara, SP, Brazil. The methods tested were: indirect instruction using 'The
      Smiling Robot' (group I), indirect instruction through class presentation (group
      II) and direct instruction with macromodels (group III). A control group was also
      constituted, which received no kind of motivation (group IV). The O'Leary Plaque
      Index was used as the evaluation method, applied before the instruction and 30
      days after application of the different methods. It was noted that the plaque
      index had not decreased in group IV only. In conclusion, all the motivation
      methods promoted significant decrease of plaque index and among these methods,
      the 'The Smiling Robot' was the one that provided the best results.

PMID- 16451507
TI  - Journal resources written for dental hygienists.

PMID- 16451508
TI  - Is your knowledge up-to-date?

PMID- 16451512
TI  - Microbiology in diagnosis and treatment planning in periodontics.
AB  - Periodontitis is considered a multifactorial infectious disease in which bacteria
      play an essential role. It has become clear that not all patients with
      periodontitis harbour the same subgingival microflora, and so far, a limited
      number of species have been recognised as indicators for progression of
      periodontal breakdown. These findings are the basis for the use of clinical
      periodontal microbiology. Microbiological information can assist in diagnosis and
      treatment planning in periodontics, and is essential for the rational use of
      topical and systemic antimicrobial treatment. Different antimicrobial regimes
      have been proposed as adjuncts to mechanical periodontal treatment. This article
      reviews the current knowledge on periodontal microbiology, different techniques
      to test for marker bacteria and the use of antibiotics in the treatment of severe
      periodontitis.

PMID- 16451513
TI  - Antiviral activity of alcohol for surface disinfection.
AB  - Bacteria and viruses from the patient's mouth travel with dental splatter and
      spills. A surface disinfectant should possess antiviral activity as well as
      antibacterial action. Because of frequent and 'open' application in the dental
      office, such a disinfectant should be non-toxic, non-allergenic and safe for the
      hygienist. It now appears that high-concentration alcohol mixtures (i.e. 80%
      ethanol + 5% isopropanol) are not only excellent antibacterials, but quickly
      inactivate HIV as well as hepatitis B and hepatitis C viruses. Compared to
      alternative surface disinfectants, use of high-concentration alcohol for the
      spray-wipe-spray method of surface disinfection in dentistry appears safe and
      efficient. However, dried matter should be wiped and hydrated first.

PMID- 16451514
TI  - How to select the right mouthrinses in periodontal prevention and therapy. Part
      I. Test systems and clinical investigations.
AB  - The use of mouthrinses is increasing, especially as adjuncts to the daily
      mechanical oral hygiene. Different test systems may and can be used to test their
      antibacterial and clinical effects: bacteriology in vitro, substantivity in vivo,
      4-day plaque re-growth, experimental gingivitis and long-term use. The plaque re
      growth investigations of a few days are not only of limited use but may also be
      dangerous because often too extensive conclusions have been drawn from their
      design. The 'gold standard' test is the experimental gingivitis model to reveal
      the antiplaque as well as the antigingivitis effects of any mouthrinse
      preparation during 3 weeks. The last kind of investigations are of several
      months' duration, where the substances are used as supplements to mechanical oral
      hygiene measures.

PMID- 16451515
TI  - Tongue coating and tongue brushing: a literature review.
AB  - The present paper reviews the role of the tongue as a habitat for oral
      microorganisms and the potential need for tongue cleaning as part of daily oral
      hygiene. In addition tongue coating is described. Many microorganisms have been
      found colonizing the dorsum of the tongue. Some studies find a positive effect to
      tongue brushing on bacterial counts on the tongue. On the other hand there are
      also studies that do not find any differences in bacterial counts before or after
      tongue brushing. Bacteria colonizing the tongue and periodontal pockets play an
      important role in the production of volatile sulphur compounds in periodontal
      health and disease. These compounds can be the cause of oral malodour. The amount
      of tongue coating in patients complaining of halitosis was significantly greater
      than in patients without halitosis. Tongue brushing on a regular basis,
      particular aiming at removing the coating on the dorsum of the tongue, has been
      found to be fruitful in reducing oral malodour. Studies investigating the role of
      tongue brushing and plaque accumulation or gingival inflammation show conflicting
      results. It is clear that the tongue forms the largest niche for microorganims in
      the oral cavity. However, on the basis of literature, there appears to be no data
      to justify the necessity to clean the tongue on a regular basis. One exception
      would be oral malodour.

PMID- 16451516
TI  - Quality assurance in health care: past, present and future.
AB  - Quality of health care delivery is a growing concern globally given current
      budget restraints and increasing demands on health care providers. The variety of
      quality assurance and quality management activities equals the numerous ways
      health care practitioners of all genres provide health care. Dental hygienists
      around the world must be knowledgeable about quality assurance and management in
      health care as it is a significant factor in the evolution of the dental hygiene
      profession and the quality of oral health care provided by dental hygienists. The
      objective of this research was to conduct a literature review on quality
      assurance and quality management. A MEDLINE search from 1966 to 2002 was
      conducted. The search resulted in approximately 145 articles. Additional
      references from works generated by the search were also obtained. The literature
      revealed information on the background and history of quality assurance and
      quality management. Much of the literature was devoted to discussions of the
      validity, reliability and effectiveness of most prominent quality management
      activities being utilised in health care today. The investigation revealed
      numerous issues and barriers surrounding quality management. This article
      concludes with suggestions for future directions of quality assurance and quality
      management.

PMID- 16451517
TI  - Status of oral healthcare in long-term care facilities.
AB  - Oral health is a fundamental component in the overall well-being and quality of
      life for elders living in long-term care facilities. Effective oral care
      interventions must not only involve recognising the importance of oral health in
      this population, but giving oral hygiene the same priority as other care
      practices in long-term care settings.

PMID- 16451518
TI  - Oral health care for pregnant and postpartum women.
AB  - Pregnancy may pose a number of concerns to the mother and the foetus. This can
      include systemic and oral issues that effect health. Transmission of caries
      causing bacteria is one problem that can be minimized by utilizing simple, cost
      effective measures. Chlorhexidine rinses and xylitol containing chewing gum will
      be discussed as possible solutions to this tremendous public health problem.

PMID- 16451520
TI  - Website update.

PMID- 16451521
TI  - Is your knowledge up-to-date?

PMID- 16451523
TI  - Origins and benefits of dental hygiene practice in Europe: the current status in
      Germany.

PMID- 16451526
TI  - Oral health trends in the US.
AB  - In the US, dental hygienists are an integral part of the health care workforce.
      Dental hygienists are prevention specialists who understand that recognising the
      association between oral and total health can prevent disease. In the US, they
      also consider it as a part of their job to detect the presence of systemic
      illnesses. Although they cannot make a medical diagnosis, they can explain their
      findings to the patients and urge them to see a physician. This report explains
      the educational requirements for a dental hygienist, barriers and access-to-care
      issues, some oral health preventive methods, among other things.

PMID- 16451527
TI  - Dental hygiene in Hong Kong: a global perspective.
AB  - PURPOSE: This article examines how dental hygiene status in Hong Kong compared to
      global developments of the profession. The aim is to address access to cost
      effective, qualified preventive care. METHODS: Information for this study was
      obtained using questionnaires and followed up by e-mail correspondence with
      International Federation of Dental Hygienists (IFDH) delegates and additional
      experts, supporting studies and reference literature. All experts consulted are
      involved in the professional and educational organisation of dental hygiene on a
      national level. RESULTS: Results show that dental hygiene is practised in about
      30 countries, generally as a licensed profession, studied at institutions of
      higher education. Average study duration is 3 years. Globally, low access to
      qualified dental hygiene care tends to be a result of a lack of social and
      cultural awareness of the benefits of preventive care and insufficient funding
      for preventive services as well as supervision requirements, which tie dental
      hygiene care to private practice dentistry settings. In several countries, a
      reduction of supervision requirements has opened the door to provide care at
      alternative settings and public health institutions. CONCLUSION: In Hong Kong,
      owing to a small number of practising dental hygienists, access to qualified
      preventive care is scarce. Public awareness of the benefits and cost
      effectiveness of preventive measures need to be raised to achieve higher
      acceptance of the profession. Global and scientific developments mandate an
      extension of study duration. Access to qualified care could be addressed by
      public health initiatives, which utilise the expertise of dental hygienists in
      setting and attaining preventive health goals.

PMID- 16451528
TI  - Dental hygienists in Korea.
AB  - The purpose of this paper is to give basic information about the status of dental
      hygienists in Korea. This paper examines the changing process of the dental
      hygiene education system in Korea, from its start in 1965 until the present,
      2003, the composition of dental personnel in Korea, the specialised areas and
      roles of dental hygienists after they receive their licenses, employment of
      dental hygienists, dental hygiene-related organisations, and the status and
      direction of dental hygienists in Korea. This paper shows the organisational,
      educational, governmental and individual efforts to increase the level of
      professionalism, education and quality of care delivered to Korean citizens
      nationwide.

PMID- 16451530
TI  - Partnerships for better oral health.
AB  - Improving oral health in populations who do not easily access the private dental
      office or the available community care site is a challenge to dental hygienists
      and others concerned with the health and well-being of all. Partnerships for
      improved oral health have been part of the community health efforts for many
      years and in many countries. With the knowledge, skills, and resources that are
      held by specific groups and organisations combined into a larger entity of a
      partnership or coalition, greater impact on oral health issue may be possible.
      Agencies and individuals interested in making improvements in oral health status
      in any particular target group may begin a process of working with others who
      have an interest in improving the health and well being of that target group. In
      a world that is increasingly synergistic and mutually dependent, improvements in
      oral health can be advanced by considering the elements of successful coalition
      building and forming partnerships with multiple organisations and individuals.

PMID- 16451531
TI  - A dental hygienist's role in tobacco cessation.
AB  - Dental professionals are uniquely poised to contribute to the battle against
      tobacco use. When tobacco users receive a consistent anti-tobacco message from a
      variety of health care providers, the likelihood of success in the battle to quit
      is increased. Most people receive many warnings in the media about the negative
      health effects of tobacco, especially those regarding cancer and heart disease.
      Smokers and smokeless tobacco users may not be as knowledgeable about the
      negative oral manifestations of tobacco use, and dental hygienists can be
      instrumental in educating their patients on these effects. Including questions
      about tobacco use in the health history is a vital first step to identifying
      patients who may benefit from tobacco intervention counselling in the dental
      office. Once identified, the hygienist can proceed to discover the patient's
      motivation to quit, and assist in providing information that may be of help to
      the patient in ceasing tobacco dependency. Helping and encouraging patients in
      their battle against tobacco use is an important way that dental hygienists can
      contribute to their patients' improved health.

PMID- 16451529
TI  - Dental hygiene's interdisciplinary relationship with dental public health: a
      position paper.
AB  - Dental hygienists' collaboration with social institutions, health-care workers
      and organisations, educational institutions, and dentistry can prevent oral
      diseases. Dental hygienists working in these organisations can reach an
      unprecedented number of people, thereby increasing preventive oral care to many
      undeserved. Working within a dental public health career increases choices and
      opportunities for the dental hygienist and benefits the public.

PMID- 16451533
TI  - Periodontal bone loss associated with an improper flossing technique: a case
      report.
AB  - PURPOSE: This article documents a case in which soft tissue and bone damage was
      associated with a long-standing habit of improper flossing. CASE DESCRIPTION: A
      33-year-old patient with excellent oral hygiene presented with gingival clefting
      and an unusual pattern of moderate angular bone loss at several sites. Previous
      radiographs suggested that some bony lesions had been present for more than 13
      years. Examination revealed no evidence that the osseous defects were related to
      chronic periodontitis or occlusal trauma. The focus of treatment for these
      chronic injuries was teaching the patient an atraumatic flossing technique.
      CONCLUSION: As the lesions had gone undiagnosed for many years, this case
      underscores the need to look for clinical signs of floss-induced damage during
      periodic examinations.

PMID- 16451534
TI  - Assessing the validity of online information.

PMID- 16451532
TI  - Comparison of modified Bass technique with normal toothbrushing practices for
      efficacy in supragingival plaque removal.
AB  - OBJECTIVES: This study was designed to compare the efficacy in supragingival
      plaque removal of normal toothbrushing practices and a particular toothbrushing
      technique, the modified Bass method. SUBJECTS AND METHODS: The research consisted
      of two identical experiments with two toothbrushing methods: the normal
      toothbrushing practices and the modified Bass technique. Forty-six secondary, non
      dental students (10 males and 36 females) with ages ranging from 18 to 30 years
      were selected. Dental plaque was assessed according to the Turesky modification
      of Quigley-Hein Index. Subjects were requested not to brush their teeth 48 h
      prior to the baseline record of plaque index. Participants were instructed to
      brush twice daily during 3 min for the duration of the 3-week trial using their
      usual toothpaste. Plaque index was recorded at 2, 7 and 21 days. RESULTS: The
      modified Bass (Mod-Bass) technique was significantly (P < 0.05) more effective in
      removing supragingival plaque than normal toothbrushing practices both in all,
      buccal and lingual sites. After 21 days, the normal practices did not
      significantly decrease mean plaque indices compared to the scores calculated
      after 7 days (P > 0.05), but did so with the modified Bass technique (P < 0.05).
      The modified Bass technique was specially efficient at the lingual sites where it
      was 2.9-fold more effective than normal practices in reducing plaque scores (P <
      0.01). CONCLUSION: The results show that a particular toothbrushing technique as
      modified Bass method is significantly superior to normal toothbrushing practices
      in supragingival plaque removal. The introduction of a specific toothbrushing
      technique, such as modified Bass technique represents an important improvement in
      the oral hygiene of the patients.

PMID- 16451535
TI  - Oral hygiene instructions.

PMID- 16451536
TI  - Case history.

PMID- 16451539
TI  - Editorial.

PMID- 16451540
TI  - The rational use of fluoride toothpaste.
AB  - Well-formulated fluoride toothpastes are clinically proven to prevent and control
      dental caries. They may also be a risk factor in the aetiology of dental
      fluorosis. This review considers the available evidence to support the
      appropriate use of fluoride toothpaste to maximise the benefit and minimise the
      risk. Three factors have an important influence on the anticaries efficacy of
      fluoride toothpaste, namely concentration, frequency of brushing and post
      brushing rinsing behaviour. The evidence suggests that low-fluoride (<600 ppm F)
      toothpastes provide less caries protection than standard (1,000 ppm F) or high
      (1,500 ppm F) concentration formulations. However, low-fluoride toothpastes are
      appropriate for very young children (under 7 years) at low caries risk,
      particularly if living in fluoridated areas. For other young children, higher
      concentrations of fluoride should be used. Brushing should be recommended twice
      daily, whilst rinsing with large volumes of water should be discouraged. Small
      amounts of toothpaste are comparable in efficacy to large amounts. The risk of
      fluorosis is associated with the ingestion of high doses of fluoride during tooth
      development and consequently only young children are at risk. The variability in
      the dose of fluoride ingested is mainly a function of the amount used, less so
      its concentration. To minimise fluorosis risk, parents should be advised to use
      only a pea-sized amount of toothpaste and encourage spitting out of excess. It is
      concluded that by using fluoride toothpastes appropriately, the benefits can be
      maximised and the risks of fluorosis minimised.

PMID- 16451541
TI  - Can we successfully maintain risk patients?
AB  - The most fundamental premise in the current view of periodontal disease is that
      not all individuals are at equal risk for disease and disease progression.
      Studies reveal that about 5-20% of the population is at risk for severe disease
      progression. The purpose of this paper is to define at-risk patients, review risk
      factors and indicators of disease progression, and outline an evidence-based
      strategy that includes both self-care and professional care for maintaining
      periodontal health. Risk factors/risk indicators considered include history of
      previous disease, increased pocket depth and loss of clinical attachment,
      frequency of dental care, specific bacterial pathogens, and
      systemic/environmental host factors such as smoking, diabetes mellitus, genetics,
      and stress. Because host factors may have more influence on disease progression
      than periodontal pathogens, personal and professional maintenance care must
      include the role of the host in periodontal disease progression. By examining the
      evidence surrounding these complex issues, dentists and dental hygienists are
      able to determine the extent to which evidence supports available approaches to
      maintain periodontal health and control disease progression.

PMID- 16451542
TI  - The making of a nation-wide campaign fighting the nursing caries.
AB  - Although, in the Netherlands, the fight against tooth decay has been successful
      over the past decades, in 1994, the incidence of nursing caries made the Ivory
      Cross(*), the Dutch National Association for the Promotion of Oral Hygiene,
      decide to develop and implement a campaign to address the phenomenon. The
      campaign is based on a two-step approach: a community strategy that exposes both
      the intermediaries and the target group to the message. It mainly focussed on
      intermediaries (step 1) such as child health clinic teams and care attendants,
      aiming to motivate and enable them to address the topic in their communication
      with parents of children aged 0-4 years (step 2). The development of this
      campaign lasted for about 1.5 years and will be described along the lines of the
      OPUS model: Orientation, Planning, execUtion and cloSure. The campaign was
      continuously assessed by means of research consisting of a pretest of materials,
      and a process and outcome evaluation. The research results gave the organisers a
      lot of information to monitor the campaign and useful insights for future
      activities.

PMID- 16451543
TI  - Percent of plaque on individual tooth surfaces and differences in plaque area
      between adjacent teeth in healthy adults.
AB  - OBJECTIVES: To apply a planimetric method to determine the percentage of the
      tooth area covered by plaque on individual tooth surfaces and to compare the
      percentage of plaque between adjacent tooth surfaces. METHODS: Forty-three
      adults, mean age 43.0 years, with no signs of periodontal disease, participated.
      The subjects underwent comprehensive professional cleaning of all teeth. The
      subjects were then instructed to maintain their ordinary oral hygiene habits.
      Plaque was registered after 1 month, on each individual tooth surface by use of
      P%I. RESULTS: The pattern of plaque accumulation was in large symmetrical, with
      differences in mean P%I between several adjacent tooth surfaces, e.g. for the
      maxillary buccal and lingual tooth surfaces between the first and second molars
      (P<0.001) and for the lingual tooth surfaces between the canines and the first
      premolars (P<0.01). CONCLUSION: In the present study, it was possible to identify
      and describe adjacent tooth surfaces with the most pronounced plaque
      accumulation, to make further improvements of oral hygiene possible.

PMID- 16451544
TI  - Origins and benefits of dental hygiene practice in Europe.
AB  - Origins and benefits of the practice of dental hygiene were investigated in order
      to provide guidelines to countries where initiatives are being taken to introduce
      the profession. In Europe, so far the profession has been introduced in the Czech
      Republic, Denmark, Great Britain, Finland, Italy, Latvia, Lithuania, the
      Netherlands, Norway, Portugal, Sweden, Switzerland and Spain. Programmes in
      Ireland, Poland, and Romania are not presented in this article. Information for
      this study was obtained using questionnaires and followed up by e-mail
      correspondence with additional experts, supporting studies and reference
      literature. All experts consulted are involved in the professional and
      educational organisation of dental hygiene in their countries. Results show that
      dentists and dental hygienists who had been inspired by the delivery of
      preventive care in the US, initiated the European dental hygiene movement. In
      some countries, opposition of organised dentistry had to be overcome. In
      countries where the population has limited access to qualified dental hygiene
      care, such as in Austria, Belgium, Germany and France, a high prevalence of
      untreated periodontal disease has been reported. There, the lucrative practice of
      delegating dental hygiene tasks to dental assistants without qualifying education
      has slowed efforts to implement the profession and resulted in negative health
      and vocational outcomes. This leads to the conclusion that an implementation of
      legislation governing the practice and the educational process of dental hygiene
      in the EU and beyond would contribute to an equitable standard of health care as
      well as to equal opportunities in education and employment.

PMID- 16451545
TI  - The discourse of dental hygiene practice in Canada.
AB  - Recently the discourse in Canada relating to dental hygiene practice has changed.
      While dentistry still exercises controlling power over the public's oral cavity,
      dental hygienists have made inroads through legislative changes. A description of
      Canadian dental hygiene practice is provided to set the stage for a discussion
      about current discourse in the dental hygiene profession. Although power is often
      perceived as a shifting changing set of relations, these can be frozen in
      abstraction. It is rather like taking a photo of a single moment or event in an
      ongoing activity. This moment provides a starting point, an event that can be
      analysed. Four such events are evident in Canadian dental hygiene practice; they
      include, education, recognition of dental hygienists as primary care providers,
      the culture of dental hygiene and self-regulation. While all the events are
      important, self-regulation is critical to the viability and development of the
      profession. It is the central event that provides the backdrop for effecting
      change. With self-regulation comes responsibility and accountability for
      professional actions. It also provides possibilities for changing the discourse
      in oral care. As oral health care discourse is transformed through legislation
      and public awareness, the public will, hopefully, be able to directly access
      dental hygiene services, and dental hygienists themselves might increasingly
      recognise their importance as contributors in the health care system.

PMID- 16451546
TI  - A collaborative approach for improving information literacy skills of dental
      hygiene students.
AB  - BACKGROUND: Evidence-based practitioners need to develop proficiency in locating
      and evaluating necessary information from a variety of sources, a concept known
      as information literacy. One potential source of information is the World Wide
      Web; however, the wide range in the quality of information available through the
      Internet indicates a need for strong critical appraisal skills. OBJECTIVES: To
      facilitate development of these skills in dental hygiene students, dental hygiene
      faculty collaborated with a librarian to implement a project to improve
      information literacy skills and integrate the use of the Internet into dental
      hygiene course work. METHODS: Students were required to develop a scenario about
      an aspect of dental hygiene practice, such as client health concern, practice
      management, or selection of an appropriate dental hygiene therapy. Students were
      to search the Internet, locate and evaluate a website that could address their
      scenario, and post this information and additional comments to a text-based
      computer conferencing section of a class website. Web CT software, particularly
      the computer conferencing function, was used to support asynchronous online
      activities. Student evaluation of the assignment was conducted using a 5-point
      Likert scale. RESULTS: Mean ratings for structure variables ranged from 3.94 to
      3.81. Slightly lower mean ratings for process variables, ranging from 3.74 to
      3.21, suggest room for improvement to activities. Mean ratings for outcome
      variables, ranging from 4.42 to 3.29, suggest achievement of the desired learning
      outcomes. CONCLUSION: Evaluation results warrant the continued inclusion of
      asynchronous online activities in conjunction with face-to-face classroom
      instruction.

PMID- 16451547
TI  - Towards international curriculum standards.
AB  - In 1998, the House of Delegates of the International Federation of Dental Hygiene
      requested that the education committee of the federation develop curriculum
      guidelines to serve as models for countries that were initiating dental hygiene
      educational programmes. This article reviews the process of guideline
      development, identifies challenges and directions for the future. A review of
      topics, goal and descriptions of 2, 3 and 4 years is presented. The process of
      development of the guidelines provided an opportunity for discussion of
      differences in dental hygiene paradigm from various countries. Participants began
      to understand the legal, cultural and educational differences that have an impact
      on curriculum for health care. It is a beginning in the process of developing
      international educational standards in dental hygiene education.

PMID- 16451548
TI  - Mobius syndrome: a dental hygiene case study and review of the literature.
AB  - Mobius syndrome, a rare, non-progressive, congenital neuromuscular disorder,
      presents with multiple dental and medical complications. Signs and symptoms of
      this condition include: congenital, bilateral or unilateral palsies of the facial
      and abducens cranial nerves (cardinal sign), and a broad scope of multisystem
      abnormalities, which may or may not include the following: opthalmoplegia
      externa, lingual palsy, clubfoot, branchial malformation, ptosis, mental
      retardation, and pectoralis muscle defect. From a dental standpoint, a number of
      anomalies may manifest, including: multiple congenitally missing teeth (both
      deciduous and permanent), micrognathia, paralysis and hypoplasia of the tongue,
      absence of facial expression and weakness of the palate. This article reviews the
      case study of a 40-year-old male client with Mobius syndrome, dental hygiene
      diagnosis (DHDx) and intervention, and the dental hygienists' responsibility and
      role in care.

PMID- 16451549
TI  - HRT, women and heart disease: facts about prevention.
AB  - In 1996, the U.S. Preventive Services Task Force (USPSTF) recommended counseling
      all perimenopausal and postmenopausal women about the potential benefits and
      harms of HRT. They determined that there was insufficient evidence to recommend
      for or against HRT for all women, but thought that individual decisions should be
      based on patient risk factors, an understanding of the probable benefits (for
      example, the prevention of myocardial infraction or fracture) and harms (for
      example, endometrial cancer with unopposed estrogen or breast cancer), and
      personal preferences. New recommendations were posted on October 23, 2002, and
      now the USPSTF recommends against the routine use of estrogen and progestin for
      the prevention of chronic conditions in postmenopausal women. The USPSTF found
      fair to good evidence that the combination of estrogen and progestin has both
      benefits and harms.

PMID- 16451550
TI  - An essential periodontal website for dental hygienists.

PMID- 16451551
TI  - Is your knowledge up to date?

PMID- 16451553
TI  - Clinical and neuropathological evolution of the hydrocephalus developed by the
      mutant mouse hyh.

PMID- 16451555
TI  - Linkage analysis of complex diseases using microsatellites and single-nucleotide
      polymorphisms: application to alcoholism.
AB  - The efficacy of linkage studies using microsatellites and single-nucleotide
      polymorphisms (SNPs) was evaluated. Analyzed data were supplied by the
      Collaborative Study on the Genetics of Alcoholism (COGA). Alcoholism was analyzed
      together with a simulated trait caused by a gene of known position, through a
      nonparametric linkage test (NPL). For the alcoholism trait, four densities of
      SNPs (1 SNP per 0.2 cM, 0.5 cM, 1 cM and 2 cM) showed higher peaks of NPL z
      scores and smaller significant p-values than the usual 10-cM density of
      microsatellites. However, the two highest densities of SNPs had unstable z score
      signals, and therefore were difficult to interpret. Analyzing a simulated trait
      with the same markers in the same pedigrees, we confirmed the higher power of all
      four densities of SNPs compared to the 10-cM microsatellites panel, although the
      existence of other confounding peaks was confirmed for maps that are denser than
      1 SNP/cM. We further showed that estimating the gene position using SNPs is far
      less biased than using the usual panel of microsatellites (biases of 0-2 cM for
      SNPs vs. 8.9 cM for microsatellites). We conclude that using dense maps of SNPs
      in linkage analysis is more powerful and less biased than using the 10-cM maps of
      microsatellites. However, linkage signals can be unstable and difficult to
      interpret when several SNPs are genotyped per centimorgan. The power and accuracy
      of 1 SNP/cM or 1 SNP/2 cM may be sufficient in a genome-wide linkage scan while
      denser maps may be most useful in fine-gene mapping studies exploiting linkage
      disequilibrium.

PMID- 16451554
TI  - Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism
      marker loci for genome-wide scans.

PMID- 16451556
TI  - Linkage disequilibrium mapping via cladistic analysis of phase-unknown genotypes
      and inferred haplotypes in the Genetic Analysis Workshop 14 simulated data.
AB  - We recently described a method for linkage disequilibrium (LD) mapping, using
      cladistic analysis of phased single-nucleotide polymorphism (SNP) haplotypes in a
      logistic regression framework. However, haplotypes are often not available and
      cannot be deduced with certainty from the unphased genotypes. One possible two
      stage approach is to infer the phase of multilocus genotype data and analyze the
      resulting haplotypes as if known. Here, haplotypes are inferred using the
      expectation-maximization (EM) algorithm and the best-guess phase assignment for
      each individual analyzed. However, inferring haplotypes from phase-unknown data
      is prone to error and this should be taken into account in the subsequent
      analysis. An alternative approach is to analyze the phase-unknown multilocus
      genotypes themselves. Here we present a generalization of the method for phase
      known haplotype data to the case of unphased SNP genotypes. Our approach is
      designed for high-density SNP data, so we opted to analyze the simulated dataset.
      The marker spacing in the initial screen was too large for our method to be
      effective, so we used the answers provided to request further data in regions
      around the disease loci and in null regions. Power to detect the disease loci,
      accuracy in localizing the true site of the locus, and false-positive error rates
      are reported for the inferred-haplotype and unphased genotype methods. For this
      data, analyzing inferred haplotypes outperforms analysis of genotypes. As
      expected, our results suggest that when there is little or no LD between a
      disease locus and the flanking region, there will be no chance of detecting it
      unless the disease variant itself is genotyped.

PMID- 16451557
TI  - Methods to test for association between a disease and a multi-allelic marker
      applied to a candidate region.
AB  - We report the analysis results of the Genetic Analysis Workshop 14 simulated
      microsatellite marker dataset, using replicate 50 from the Danacaa population. We
      applied several methods for association analysis of multi-allelic markers to case
      control data to study the association between Kofendrerd Personality Disorder and
      multi-allelic markers in a candidate region previously identified by the linkage
      analysis. Evidence for association was found for marker D03S0127 (p < 0.01). The
      analyses were done without any prior knowledge of the answers.

PMID- 16451558
TI  - Identification of susceptibility loci for complex diseases in a case-control
      association study using the Genetic Analysis Workshop 14 dataset.
AB  - Although current methods in genetic epidemiology have been extremely successful
      in identifying genetic loci responsible for Mendelian traits, most common
      diseases do not follow simple Mendelian modes of inheritance. It is important to
      consider how our current methodologies function in the realm of complex diseases.
      The aim of this study was to determine the ability of conventional association
      methods to fine map a locus of interest. Six study populations were selected from
      10 replicates (New York) from the Genetic Analysis Workshop 14 simulated dataset
      and analyzed for association between the disease trait and locus D2. Genotypes
      from 45 single-nucleotide polymorphisms in the telomeric region of chromosome 3
      were analyzed by Pearson's chi-square tests for independence to test for
      association with the disease trait of interest. A significant association was
      detected within the region; however, it was found 3 cM from the documented
      location of the D2 disease locus. This result was most likely due to the method
      used for data simulation. In general, this study showed that conventional case
      control association methods could detect disease loci responsible for the
      development of complex traits.

PMID- 16451559
TI  - Comparisons of case-selection approaches based on allele sharing and/or disease
      severity index: application to the GAW14 simulated data.
AB  - For mapping complex disease traits, linkage studies are often followed by a case
      control association strategy in order to identify disease-associated genes/single
      nucleotide polymorphisms (SNPs). Substantial efforts are required in selecting
      the most informative cases from a large collection of affected individuals in
      order to maximize the power of the study, while taking into consideration study
      cost. In this article, we applied and extended three case-selection strategies
      that use allele-sharing information method for families with multiple affected
      offspring to select most informative cases using additional information on
      disease severity. Our results revealed that most significant associations, as
      measured by the lowest p-values, were obtained from a strategy that selected a
      case with the most allele sharing with other affected sibs from linked families
      ("linked-best"), despite reduction in sample size resulting from discarding
      unlinked families. Moreover, information on disease severity appears to be useful
      to improve the ability to detect associations between markers and disease loci.

PMID- 16451560
TI  - Hierarchical modeling in association studies of multiple phenotypes.
AB  - The genetic study of disease-associated phenotypes has become common because such
      phenotypes are often easier to measure and in many cases are under greater
      genetic control than the complex disease itself. Some disease-associated
      phenotypes are rare, however, making it difficult to evaluate their effects due
      to small informative sample sizes. In addition, analyzing numerous phenotypes
      introduces the issue of multiple comparisons. To address these issues, we have
      developed a hierarchical model (HM) for multiple phenotypes that provides more
      accurate effect estimates with a lower false-positive rate. We evaluated the
      validity and power of HM in association studies of multiple phenotypes using
      randomly selected cases and controls from the simulated data set in the Genetic
      Analysis Workshop 14. In particular, we first analyzed the association between
      each of the 12 subclinical phenotypes and single-nucleotide polymorphisms within
      the known causal loci using a conventional logistic regression model (LRM). Then
      we added a second-stage model by regressing all of the logistic coefficients of
      the phenotypes obtained from LRM on a Z matrix that incorporates the clinical
      correlation of the phenotypes. Specially, the 12 phenotypes were grouped into 3
      clusters: 1) communally shared emotions; 2) behavioral related; and 3) anxiety
      related. A semi-Bayes HM effect estimate for each phenotype was calculated and
      compared with those from LRM. We observed that using HM to evaluate the
      association between SNPs and multiple related phenotypes slightly increased power
      for detecting the true associations and also led to fewer false-positive results.

PMID- 16451562
TI  - Combining evidence for association from transmission disequilibrium and case
      control studies using single-nucleotide polymorphisms.
AB  - The aim of the present analysis is to combine evidence for association from the
      two most commonly used designs in genetic association analysis, the case-control
      design and the transmission disequilibrium test (TDT) design. The cases here are
      affected offspring from nuclear families and are used in both the case-control
      and TDT designs. As a result, inference from these designs is not independent. We
      applied a simple logistic regression method for combining evidence for
      association from case-control and TDT designs to single-nucleotide polymorphism
      data purchased on a region on chromosome 3, replicate 1 of the Aipotu population.
      Combining the evidence from the case-control and TDT designs yielded a 5-10%
      reduction in the standard errors of the relative risk estimates. The authors did
      not know the results before the analyses were conducted.

PMID- 16451561
TI  - Selecting cases from nuclear families for case-control association analysis.
AB  - We examine the efficiency of a number of schemes to select cases from nuclear
      families for case-control association analysis using the Genetic Analysis
      Workshop 14 simulated dataset. We show that with this simulated dataset comparing
      all affected siblings with unrelated controls is considerably more powerful than
      all of the other approaches considered. We find that the test statistic is
      increased by almost 3-fold compared to the next best sampling schemes of
      selecting all affected sibs only from families with affected parents (AF aff),
      one affected sib with most evidence of allele-sharing from each family (SF), and
      all affected sibs from families with evidence for linkage (AF L). We consider
      accounting for biological relatedness of samples in the association analysis to
      maintain the correct type I error. We also discuss the relative efficiencies of
      increasing the ratio of unrelated cases to controls, methods to confirm
      associations and issues to consider when applying our conclusions to other
      complex disease datasets.

PMID- 16451563
TI  - Robust trend tests for genetic association in case-control studies using family
      data.
AB  - We studied a trend test for genetic association between disease and the number of
      risk alleles using case-control data. When the data are sampled from families,
      this trend test can be adjusted to take into account the correlations among
      family members in complex pedigrees. However, the test depends on the scores
      based on the underlying genetic model and thus it may have substantial loss of
      power when the model is misspecified. Since the mode of inheritance will be
      unknown for complex diseases, we have developed two robust trend tests for case
      control studies using family data. These robust tests have relatively good power
      for a class of possible genetic models. The trend tests and robust trend tests
      were applied to a dataset of Genetic Analysis Workshop 14 from the Collaborative
      Study on the Genetics of Alcoholism.

PMID- 16451564
TI  - How to quantify information loss due to phase ambiguity in haplotype case-control
      studies.
AB  - Assigning haplotypes in a case-control study is a challenging problem. We
      proposed a method to quantify the information loss due to missing phase
      information. We determined which individuals were responsible for the information
      loss, and calculated how much information could be gained when the ambiguous
      individuals could be resolved by adding additional parental information.

PMID- 16451565
TI  - Effects of population structure on genetic association studies.
AB  - Population-based case-control association is a promising approach for unravelling
      the genetic basis of complex diseases. One potential problem of this approach is
      the presence of population structure in the samples. Using the Collaborative
      Study on the Genetics of Alcoholism (COGA) single-nucleotide polymorphism (SNP)
      datasets, we addressed three questions: How can the degree of population
      structure be quantified, and how does the population structure affect association
      studies? How accurate and efficient is the genomic control method in correcting
      for population structure? The amount of population structure in the COGA SNP data
      was found to inflate the p-value in association tests. Genomic control was found
      to be effective only when the appropriate number of markers was used in the
      control group in order to correctly calibrate the test. The approach presented in
      this paper could be used to select the appropriate number of markers for use in
      the genomic control method of correcting population structure.

PMID- 16451566
TI  - Comparison of marker types and map assumptions using Markov chain Monte Carlo
      based linkage analysis of COGA data.
AB  - We performed multipoint linkage analysis of the electrophysiological trait ECB21
      on chromosome 4 in the full pedigrees provided by the Collaborative Study on the
      Genetics of Alcoholism (COGA). Three Markov chain Monte Carlo (MCMC)-based
      approaches were applied to the provided and re-estimated genetic maps and to five
      different marker panels consisting of microsatellite (STRP) and/or SNP markers at
      various densities. We found evidence of linkage near the GABRB1 STRP using all
      methods, maps, and marker panels. Difficulties encountered with SNP panels
      included convergence problems and demanding computations.

PMID- 16451567
TI  - A new family-based association test via a least-squares method.
AB  - To test the association between a dichotomous phenotype and genetic marker based
      on family data, we propose a least-squares method using the vector of phenotypes
      and their cross products within each family. This new approach allows covariate
      adjustment and is numerically much simpler to implement compared to likelihood-
      based methods. The new approach is asymptotically equivalent to the generalized
      estimating equation approach with a diagonal working covariance matrix, thus
      avoiding some difficulties with the working covariance matrix reported previously
      in the literature. When applied to the data from Collaborative Study on the
      Genetics of Alcoholism, this new method shows a significant association between
      the marker rs1037475 and alcoholism.

PMID- 16451568
TI  - Smoothing of the bivariate LOD score for non-normal quantitative traits.
AB  - Variance component analysis provides an efficient method for performing linkage
      analysis for quantitative traits. However, type I error of variance components
      based likelihood ratio testing may be affected when phenotypic data are non
      normally distributed (especially with high values of kurtosis). This results in
      inflated LOD scores when the normality assumption does not hold. Even though
      different solutions have been proposed to deal with this problem with univariate
      phenotypes, little work has been done in the multivariate case. We present an
      empirical approach to adjust the inflated LOD scores obtained from a bivariate
      phenotype that violates the assumption of normality. Using the Collaborative
      Study on the Genetics of Alcoholism data available for the Genetic Analysis
      Workshop 14, we show how bivariate linkage analysis with leptokurtotic traits
      gives an inflated type I error. We perform a novel correction that achieves
      acceptable levels of type I error.

PMID- 16451569
TI  - Identification of genes involved in alcohol consumption and cigarettes smoking.
AB  - We compared the results of quantitative linkage analysis using single-nucleotide
      polymorphisms and microsatellite markers and introduced a new screening test for
      multivariate quantitative linkage analysis using the Collaborative Study on the
      Genetics of Alcoholism data. We analyzed 115 extended non-Hispanic White families
      and tested for linkage using two phenotypes: the maximum number of drinks in a 24
      hour period and the number of packs smoked per day for one year. Our results
      showed that the linkage signal increased using single-nucleotide polymorphisms
      compared with microsatellite markers and that the screening test gave similar
      results to that of the bivariate analysis, suggesting its potential use in
      reducing overall analysis time.

PMID- 16451570
TI  - A power study of bivariate LOD score analysis of a complex trait and
      fear/discomfort with strangers.
AB  - Complex diseases are often reported along with disease-related traits (DRT).
      Sometimes investigators consider both disease and DRT phenotypes separately and
      sometimes they consider individuals as affected if they have either the disease
      or the DRT, or both. We propose instead to consider the joint distribution of the
      disease and the DRT and do a linkage analysis assuming a pleiotropic model. We
      evaluated our results through analysis of the simulated datasets provided by
      Genetic Analysis Workshop 14. We first conducted univariate linkage analysis of
      the simulated disease, Kofendrerd Personality Disorder and one of its simulated
      associated traits, phenotype b (fear/discomfort with strangers). Subsequently, we
      considered the bivariate phenotype, which combined the information on Kofendrerd
      Personality Disorder and fear/discomfort with strangers. We developed a program
      to perform bivariate linkage analysis using an extension to the Elston-Stewart
      peeling method of likelihood calculation. Using this program we considered the
      microsatellites within 30 cM of the gene pleiotropic for this simulated disease
      and DRT. Based on 100 simulations of 300 families we observed excellent power to
      detect linkage within 10 cM of the disease locus using the DRT and the bivariate
      trait.

PMID- 16451571
TI  - Bivariate genome scans incorporating factor and principal component analyses to
      identify common genetic components of alcoholism, event-related potential, and
      electroencephalogram phenotypes.
AB  - Genetic components significantly contribute to the susceptibilities of alcoholism
      and its endophenotypes, such as event-related potential measures and
      electroencephalogram. An endophenotype is a correlated trait which identifies
      individuals at risk. Correlated traits could be influenced by shared genes. This
      study is intended to identify chromosome regions that may harbor common genetic
      loci contributing to alcoholism, event related potential measures and
      electroencephalogram. All 143 Collaborative Study on the Genetics of Alcoholism
      families with 1,614 individuals provided by the Genetic Analysis Workshop 14 were
      used for the analysis with aldx1 as an alcoholism diagnosis. We carried out
      factor and principal component analyses on the 12 event-related potentials, then
      bivariate genome scans on aldx1 and electroencephalogram (ecb21), as well as
      alcoholism and the principal component scores of the event-related potential
      measures. A univariate genome scan was also carried out on each trait. Factor and
      principal component analysis on the event-related potential measures showed that
      the 4 ttths and 4 ntths belong to one cluster (cluster 1), while the 4 ttdts
      belonged to another (cluster 2). From each cluster, one principal component was
      extracted and saved as pc1 (for cluster 1) and pc2 (for cluster 2). The results
      of genome scans revealed only one chromosome region, chromosome 4 q at about 100
      cM, identified by several univariate genome scans including aldx1, ecb21, and
      pc2, and the evidence of linkage increased significantly in the bivariate genome
      scans of aldx1 and ecb21 and aldx1 and pc2. Our study suggests that the same
      quantitative trait locus on the chromosome 4 q region, where ADH3 is located, may
      influence the risk of alcoholism, variations of electroencephalogram, and the 4
      ttdts of the event-related potential measures.

PMID- 16451572
TI  - Genomic screening in family-based association testing.
AB  - Due to the recent gains in the availability of single-nucleotide polymorphism
      data, genome-wide association testing has become feasible. It is hoped that this
      additional data may confirm the presence of disease susceptibility loci, and
      identify new genetic determinants of disease. However, the problem of multiple
      comparisons threatens to diminish any potential gains from this newly available
      data. To circumvent the multiple comparisons issue, we utilize a recently
      developed screening technique using family-based association testing. This
      screening methodology allows for the identification of the most promising single
      nucleotide polymorphisms for testing without biasing the nominal significance
      level of our test statistic. We compare the results of our screening technique
      across univariate and multivariate family-based association tests. From our
      analyses, we observe that the screening technique, applied to different settings,
      is fairly consistent in identifying optimal markers for testing. One of the
      identified markers, TSC0047225, was significantly associated with both the ttth1
      (p = 0.004) and ttth1-ttth4 (p = 0.004) phenotype(s). We find that both
      univariate- and multivariate-based screening techniques are powerful tools for
      detecting an association.

PMID- 16451573
TI  - A Bayesian genome screening of maximum number of drinks as an alcoholism
      phenotype with the new Haseman-Elston method.
AB  - Common human disorders, such as alcoholism, may be the result of interactions of
      many genes as well as environmental risk factors. Therefore, it is important to
      incorporate gene x gene and gene x environment interactions in complex disease
      gene mapping. In this study, we applied a robust Bayesian genome screening method
      that can incorporate interaction effects to map genes underlying alcoholism
      through its application to the data of the Collaborative Studies on Genetics of
      Alcoholism provided by Genetic Analysis Workshop 14. Our Bayesian genome
      screening method uses the regression-based stochastic variable selection, coupled
      with the new Haseman-Elston method to identify markers linked to phenotypes of
      interest. Compared to traditional linkage methods based on single-gene disease
      models, our method allows for multilocus disease models for simultaneous
      screening including both main and interaction (epistatic) effects. It is
      conceptually simple and computationally efficient through the use of Gibbs
      sampler. We conducted genome-wide analysis and comparison between scans based on
      microsatellites and single-nucleotide polymorphisms. A total of 328
      microsatellites and 11,560 single-nucleotide polymorphisms (by Affymetrix) on 22
      autosomal chromosomes and sex chromosome were used.

PMID- 16451574
TI  - A comparison of univariate, bivariate, and trivariate whole-genome linkage
      screens of genetically correlated electrophysiological endophenotypes.
AB  - We used a maximum-likelihood based multipoint linkage approach implemented in
      SOLAR to examine simultaneously linkage for three electrophysiological
      endophenotypes from the Collaborative Study of the Genetics of Alcoholism: TTTH1,
      TTTH2, and TTTH3. These endophenotypes have been identified as markers of alcohol
      dependence susceptibility. Data were from 905 individuals in 143 families.
      Measured covariates considered included sex, age at electrophysiology data
      collection, habitual smoking status, and the maximum number of drinks consumed in
      a 24-hour period. Comparisons were made among genome-wide univariate, bivariate,
      and trivariate linkage analyses using genotypes based on microsatellite markers
      supplied by the Center for Inherited Disease Research, and genotypes based on
      single-nucleotide polymorphism markers provided by Illumina. All LODs were
      corrected to a standard equivalent to 1 degree of freedom. Using the trivariate
      approach and the microsatellite-based genotypes, we estimated a maximum
      multipoint linkage signal of LOD = 2.66 on chromosome 7q at 157 cM. Analyses
      using the Illumina SNP genotypes produced similar results, yielding a maximum
      multipoint LOD of 2.95 on 7q at 174 cM. These regions of interest correspond to
      those identified in the univariate and bivariate linkage screens. Our results
      suggest that trivariate multipoint linkage analyses have utility in the further
      characterization of chromosomal regions potentially containing genes influencing
      the phenotypes being examined. Based on a comparison of the number of LOD scores
      achieving statistical significance, our results suggest that the microsatellite-
      and Illumina SNP-based genotypes have similar utility for detecting genomic
      regions of interest.

PMID- 16451575
TI  - Multivariate linkage analysis using the electrophysiological phenotypes in the
      COGA alcoholism data.
AB  - Multivariate linkage analysis using several correlated traits may provide greater
      statistical power to detect susceptibility genes in loci whose effects are too
      small to be detected in univariate analysis. In this analysis, we apply a new
      approach and perform a linkage analysis of several electrophysiological
      phenotypes of the Collaborative Study on the Genetics of Alcoholism data of the
      Genetic Analysis Workshop 14. Our approach is based on a variance-component model
      to map candidate genes using repeated or longitudinal measurements. It can take
      into account covariate effects and time-dependent genetic effects in general
      pedigree data. We compare our results with the ones obtained by SOLAR using
      single measurement data. Our multivariate linkage analysis found linkage evidence
      on two regions on chromosome 4: around marker GABRB1 at 51.4 cM and marker FABP2
      at 116.8 cM (unadjusted p-value = 0.00006).

PMID- 16451576
TI  - Genes, age, and alcoholism: analysis of GAW14 data.
AB  - A genetic analysis of age of onset of alcoholism was performed on the
      Collaborative Study on the Genetics of Alcoholism data released for Genetic
      Analysis Workshop 14. Our study illustrates an application of the log-normal age
      of onset model in our software Genetic Epidemiology Models (GEMs). The phenotype
      ALDX1 of alcoholism was studied. The analysis strategy was to first find the
      markers of the Affymetrix SNP dataset with significant association with age of
      onset, and then to perform linkage analysis on them. ALDX1 revealed strong
      evidence of linkage for marker tsc0041591 on chromosome 2 and suggestive linkage
      for marker tsc0894042 on chromosome 3. The largest separation in mean ages of
      onset of ALDX1 was 19.76 and 24.41 between male smokers who are carriers of the
      risk allele of tsc0041591 and the non-carriers, respectively. Hence, male smokers
      who are carriers of marker tsc0041591 on chromosome 2 have an average onset of
      ALDX1 almost 5 years earlier than non-carriers.

PMID- 16451577
TI  - Genome-wide linkage analysis of age at onset of alcohol dependence: a comparison
      between microsatellites and single-nucleotide polymorphisms.
AB  - BACKGROUND: Using the dataset provided for Genetic Analysis Workshop 14 by the
      Collaborative Study on the Genetics of Alcoholism, we performed genome-wide
      linkage analysis of age at onset of alcoholism to compare the utility of
      microsatellites and single-nucleotide polymorphisms (SNPs) in genetic linkage
      study. METHODS: A multipoint nonparametric variance component linkage analysis
      method was applied to the survival distribution function obtained from
      semiparametric proportional hazards model of the age at onset phenotype of
      alcoholism. Three separate linkage analyses were carried out using 315
      microsatellites, 2,467 and 9,467 SNPs, spanning the 22 autosomal chromosomes.
      RESULTS: Heritability of age at onset was estimated to be approximately 12% (p <
      0.001). We observed weak correlation, both in trend and strength, of genome-wide
      linkage signals between microsatellites and SNPs. Results from SNPs revealed more
      and stronger linkage signals across the genome compared with those from
      microsatellites. The only suggestive evidence of linkage from microsatellites was
      on chromosome 1 (LOD of 1.43). Differences in map densities between the two sets
      of SNPs used in this study did not appear to confer an advantage in terms of
      strength of linkage signals. CONCLUSION: Our study provided support for better
      performance of dense SNP maps compared with the sparse microsatellite maps
      currently available for linkage analysis of quantitative traits. This better
      performance could be attributable to precise definition and high map resolutions
      achievable with dense SNP maps, thus resulting in increased power to detect
      possible loci affecting given trait or disease.

PMID- 16451578
TI  - Effect of genotype x alcoholism interaction on linkage analysis of an alcoholism
      related quantitative phenotype.
AB  - Studies have shown that genetic and environmental factors and their interactions
      affect several alcoholism phenotypes. Genotype x alcoholism (GxA) interaction
      refers to the environmental (alcoholic and non-alcoholic) influences on the
      autosomal genes contributing to variation in an alcoholism-related quantitative
      phenotype. The purpose of this study was to examine the effects of GxA
      interaction on the detection of linkage for alcoholism-related phenotypes. We
      used phenotypic and genotypic data from the Collaborative Study on the Genetics
      of Alcoholism relating to 1,388 subjects as part of Genetic Analysis Workshop 14
      problem 1. We analyzed the MXDRNK phenotype to detect GxA interaction using
      SOLAR. Upon detecting significant interaction, we conducted variance-component
      linkage analyses using microsatellite marker data. For maximum number of drinks
      per a 24 hour period, the highest LODs were observed on chromosomes 1, 4, and 13
      without GxA interaction. Interaction analysis yielded four regions on chromosomes
      1, 4, 13, and 15. On chromosome 4, a maximum LOD of 1.5 at the same location as
      the initial analysis was obtained after incorporating GxA interaction effects.
      However, after correcting for extra parameters, the LOD score was reduced to a
      corrected LOD of 1.1, which is similar to the LOD observed in the non-interaction
      analysis. Thus, we see little differences in LOD scores, while some linkage
      regions showed large differences in the magnitudes of estimated quantitative
      trait loci heritabilities between the alcoholic and non-alcoholic groups. These
      potential hints of differences in genetic effect may influence future analyses of
      variants under these linkage peaks.

PMID- 16451579
TI  - Two novel quantitative trait linkage analysis statistics based on the posterior
      probability of linkage: application to the COGA families.
AB  - BACKGROUND: In this paper we apply two novel quantitative trait linkage
      statistics based on the posterior probability of linkage (PPL) to chromosome 4
      from the GAW 14 COGA dataset. Our approaches are advantageous since they use the
      full likelihood, use full phenotypic information, do not assume normality at the
      population level or require population/sample parameter estimates; and like other
      forms of the PPL, they are specifically tailored to accumulate linkage evidence,
      either for or against linkage, across multiple sets of heterogeneous data.
      RESULTS: The first statistic uses all quantitative trait (QT) information from
      the pedigree (QT-posterior probability of linkage, PPL); we applied the QT-PPL to
      the trait ecb21 (resting electroencephalogram). The second statistic allows
      simultaneous incorporation of dichotomous trait data into the QT analysis via a
      threshold model (QTT-PPL); we applied the QTT-PPL to combined data on ecb21 and
      ALDX1. We obtained a QT-PPL of 96% at GABRB1 and a QT-PPL of 18% at FABP2 while
      the QTT-PPL was 4% and 2% at the same two loci, respectively. By comparison, the
      variance-components (VC) method, as implemented in SOLAR, yielded multipoint VC
      LOD scores of 2.05 and 2.21 at GABRB1 and FABP2, respectively; no other VC LODs
      were greater than 2. CONCLUSION: The QTT-PPL was only 4% at GABARB1, which might
      suggest that the underlying ecb21 gene does not also cause ALDX1, although
      features of the data complicate interpretation of this result.

PMID- 16451580
TI  - Microsatellites versus single-nucleotide polymorphisms in linkage analysis for
      quantitative and qualitative measures.
AB  - BACKGROUND: Genetic maps based on single-nucleotide polymorphisms (SNP) are
      increasingly being used as an alternative to microsatellite maps. This study
      compares linkage results for both types of maps for a neurophysiology phenotype
      and for an alcohol dependence phenotype. Our analysis used two SNP maps on the
      Illumina and Affymetrix platforms. We also considered the effect of high linkage
      disequilibrium (LD) in regions near the linkage peaks by analysing a "sparse" SNP
      map obtained by dropping some markers in high LD with other markers in those
      regions. RESULTS: The neurophysiology phenotype at the main linkage peak near 130
      MB gave LOD scores of 2.76, 2.53, 3.22, and 2.68 for the microsatellite,
      Affymetrix, Illumina, and Illumina-sparse maps, respectively. The alcohol
      dependence phenotype at the main linkage peak near 101 MB gave LOD scores of
      3.09, 3.69, 4.08, and 4.11 for the microsatellite, Affymetrix, Illumina, and
      Illumina-sparse maps, respectively. CONCLUSION: The linkage results were stronger
      overall for SNPs than for microsatellites for both phenotypes. However, LOD
      scores may be artificially elevated in regions of high LD. Our analysis indicates
      that appropriately thinning a SNP map in regions of high LD should give more
      accurate LOD scores. These results suggest that SNPs can be an efficient
      substitute for microsatellites for linkage analysis of both quantitative and
      qualitative phenotypes.

PMID- 16451581
TI  - Quantitative trait locus-specific genotype x alcoholism interaction on linkage
      for evoked electroencephalogram oscillations.
AB  - We explored the evidence for a quantitative trait locus (QTL)-specific genotype x
      alcoholism interaction for an evoked electroencephalogram theta band oscillation
      (ERP) phenotype on a region of chromosome 7 in participants of the US
      Collaborative Study on the Genetics of Alcoholism. Among 901 participants with
      both genotype and phenotype data available, we performed variance component
      linkage analysis (SOLAR version 2.1.2) in the full sample and stratified by DSM
      III-R and Feighner-definite alcoholism categories. The heritability of the ERP
      phenotype after adjusting for age and sex effects in the combined sample and in
      the alcoholism classification sub-groups ranged from 40% to 66%. Linkage on
      chromosome 7 was identified at 158 cM (LOD = 3.8) in the full sample and at 108
      in the non-alcoholic subgroup (LOD = 3.1). Further, we detected QTL-specific
      genotype x alcoholism interaction at these loci. This work demonstrates the
      importance of considering the complexity of common complex traits in our search
      for genes that predispose to alcoholism.

PMID- 16451583
TI  - COGA phenotypes and linkages on chromosome 2.
AB  - An initial linkage analysis of the alcoholism phenotype as defined by DSM-III-R
      criteria and alcoholism defined by DSM-IV criteria showed many, sometimes
      striking, inconsistencies. These inconsistencies are greatly reduced by making
      the definition of alcoholism more specific. We defined new phenotypes combining
      the alcoholism definitions and the latent variables, defining an individual as
      affected if that individual is alcoholic under one of the definitions (either DSM
      III-R or DSM-IV), and indicated having a symptom defined by one of the latent
      variables. This was done for each of the two alcoholism definitions and five
      latent variables, selected from a canonical discriminant analyses indicating they
      formed significant groupings using the electrophysiological variables. We found
      that linkage analyses utilizing these latent variables were much more robust and
      consistent than the linkage results based on DSM-III-R or DSM-IV criteria for
      definition of alcoholism. We also performed linkage analyses on two first
      principal components derived phenotypes, one derived from the
      electrophysiological variables, and the other derived from the latent variables.
      A region on chromosome 2 at 250 cM was found to be linked to both of these
      derived phenotypes. Further examination of the SNPs in this region identified
      several haplotypes strongly associated with these derived phenotypes.

PMID- 16451582
TI  - Genetic analysis of the maximum drinks phenotype.
AB  - Using data provided by the Collaborative Study on the Genetics of Alcoholism we
      studied the genetics of a quantitative trait: the maximum number of drinks
      consumed in a 24-hour period. A two-stage method was used. First, linkage
      analysis was performed, followed by association analysis in regions where linkage
      was detected. Additionally, the extent of linkage disequilibrium among single
      nucleotide polymorphisms (SNP) associated with the phenotype was assessed.
      Linkage to chromosomes 2 and 7 was detected, and follow-up association analysis
      found multiple trait-associated SNPs in the chromosome 7 linkage region.
      Chromosome 4, which has been implicated in previous studies of the maximum drinks
      phenotype, did not pass our threshold for linkage evidence in stage 1, but
      secondary analyses of this chromosome indicated modest evidence for both linkage
      and association. The evidence suggests that chromosome 7 may harbor an additional
      locus influencing the maximum drinks consumption phenotype.

PMID- 16451584
TI  - A study of genetic association with electrophysiological measures related to
      alcoholism: GAW14 data.
AB  - Recently, alcohol-related traits have been shown to have a genetic component.
      Here, we study the association of specific genetic measures in one of the three
      sets of electrophysiological measures in families with alcoholism distributed as
      part of the Genetic Analysis Workshop 14 data, the NTTH (non-target case of
      Visual Oddball experiment for 4 electrode placements) phenotypes: ntth1, ntth2,
      ntth3, and ntth4. We focused on the analysis of the 786 Affymetrix markers on
      chromosome 4. Our desire was to find at least a partial answer to the question of
      whether ntth1, ntth2, ntth3, and ntth4 are separately or jointly genetically
      controlled, so we studied the principal components that explain most of the
      covariation of the four quantitative traits. The first principal component, which
      explains 70% of the covariation, showed association but not genetic linkage to
      two markers: tsc0272102 and tsc0560854. On the other hand, ntth1 appeared to be
      the trait driving the variation in the second principal component, which showed
      association and genetic linkage at markers in four regions: tsc0045058,
      tsc1213381, tsc0055068, and tsc0051777 at map distances 53.26, 85.42, 89.31, and
      172.86, respectively. These results show that the partial answer to our starting
      question for this brief analysis is that the NTTH phenotypes are not jointly
      genetically controlled. The component ntth1 displays marked genetic linkage.

PMID- 16451585
TI  - Mixed-effects Cox models of alcohol dependence in extended families.
AB  - The presence of disease is commonly used in genetic studies; however, the time to
      onset often provides additional information. To apply the popular Cox model for
      such data, it is desirable to consider the familial correlation, which involves
      kinship or identity by descent (IBD) information between family members.
      Recently, such a framework has been developed and implemented in a UNIX-based S
      PLUS package called kinship, extending the Cox model with mixed effects and
      familial relationship. The model is of great potential in joint analysis of
      family data with genetic and environmental factors. We apply this framework to
      data from the Collaborative Study on the Genetics of Alcoholism data as part of
      Genetic Analysis Workshop 14. We use the S-PLUS package, ported into the R
      environment http://www.r-project.org, for the analysis of microsatellite data on
      chromosomes 4 and 7. In these analyses, IBD information at those markers is used
      in addition to the basic Cox model with mixed effects, which provides estimates
      of the relative contribution of specific genetic markers. D4S1645 had the largest
      variance and contribution to the log-likelihood on chromosome 4, but the
      significance of this finding requires further investigation.

PMID- 16451586
TI  - A genome-wide linkage and association study using COGA data.
AB  - BACKGROUND: Genome-wide association will soon be available to use as an adjunct
      to traditional linkage analysis. We studied alcoholism in 119 families collected
      by the Collaborative Study on the Genetics of Alcoholism and made available in
      Genetic Analysis Workshop 14, using genome-wide linkage and association analyses.
      METHODS: Genome-wide linkage analysis was first performed using microsatellite
      markers and a region with the strongest linkage evidence was further analyzed
      using single-nucleotide polymorphisms (SNPs). Family based genome-wide
      association test was also conducted using the SNPs. RESULTS: Nonparametric
      linkage analysis revealed weak linkage evidence on chromosome 7, and association
      analysis identified SNP tsc0515272 on chromosome 3 as significantly associated
      with alcoholism. CONCLUSION: Linkage analysis may require large sample sizes and
      high quality genotyping and marker maps to adequately improve power, while
      association analysis could hold more promise in efforts to identify variants
      responsible for complex traits.

PMID- 16451587
TI  - An artificial neural network for estimating haplotype frequencies.
AB  - The problem of estimating haplotype frequencies from population data has been
      considered by numerous investigators, resulting in a wide variety of possible
      algorithmic and statistical solutions. We propose a relatively unique approach
      that employs an artificial neural network (ANN) to predict the most likely
      haplotype frequencies from a sample of population genotype data. Through an
      innovative ANN design for mapping genotype patterns to diplotypes, we have
      produced a prototype that demonstrates the feasibility of this approach, with
      provisional results that correlate well with estimates produced by the
      expectation maximization algorithm for haplotype frequency estimation. Given the
      computational demands of estimating haplotype frequencies for 20 or more single
      nucleotide polymorphisms, the ANN approach is promising because its design fits
      well with parallel computing architectures.

PMID- 16451588
TI  - Comparing single-nucleotide polymorphism marker-based and microsatellite marker
      based linkage analyses.
AB  - We compared linkage analysis results for an alcoholism trait, ALDX1 (DSM-III-R
      and Feigner criteria) using a nonparametric linkage analysis method, which takes
      into account allele sharing among several affected persons, for both
      microsatellite and single-nucleotide polymorphism (SNP) markers (Affymetrix and
      Illumina) in the Collaborative Study on the Genetics of Alcoholism (COGA) dataset
      provided to participants at the Genetic Analysis Workshop 14 (GAW14). The two
      sets of linkage results from the dense Affymetrix SNP markers and less densely
      spaced Illumina SNP markers are very similar. The linkage analysis results from
      microsatellite and SNP markers are generally similar, but the match is not
      perfect. Strong linkage peaks were found on chromosome 7 in three sets of linkage
      analyses using both SNP and microsatellite marker data. We also observed that for
      SNP markers, using the given genetic map and using the map by converting 1
      megabase pair (1 Mb) to 1 centimorgan (cM), did not change the linkage results.
      We recommend the use of the 1 Mb-to-1 cM converted map in a first round of
      linkage analysis with SNP markers in which map integration is an issue.

PMID- 16451589
TI  - Whole-genome association studies on alcoholism comparing different phenotypes
      using single-nucleotide polymorphisms and microsatellites.
AB  - Alcoholism is a complex disease. As with other common diseases, genetic variants
      underlying alcoholism have been illusive, possibly due to the small effect from
      each individual susceptible variant, gene x environment and gene x gene
      interactions and complications in phenotype definition. We conducted association
      tests, the family-based association tests (FBAT) and the backward haplotype
      transmission association (BHTA), on the Collaborative Study of the Genetics of
      Alcoholism (COGA) data provided by Genetic Analysis Workshop (GAW) 14. Efron's
      local false discovery rate method was applied to control the proportion of false
      discoveries. For FBAT, we compared the results based on different types of
      genetic markers (single-nucleotide polymorphisms (SNPs) versus microsatellites)
      and different phenotype definitions (clinical diagnoses versus
      electrophysiological phenotypes). Significant association results were found only
      between SNPs and clinical diagnoses. In contrast, significant results were found
      only between microsatellites and electrophysiological phenotypes. In addition, we
      obtained the association results for SNPs and microsatellites using COGA
      diagnosis as phenotype based on BHTA. In this case, the results for SNPs and
      microsatellites are more consistent. Compared to FBAT, more significant markers
      are detected with BHTA.

PMID- 16451590
TI  - Diagnosis of alcoholism based on neural network analysis of phenotypic risk
      factors.
AB  - BACKGROUND: Alcoholism is a serious public health problem. It has both genetic
      and environmental causes. In an effort to gain understanding of the underlying
      genetic susceptibility to alcoholism, a long-term study has been undertaken. The
      Collaborative Study on the Genetics of Alcoholism (COGA) provides a rich source
      of genetic and phenotypic data. One ongoing problem is the difficulty of reliably
      diagnosing alcoholism, despite many known risk factors and measurements. We have
      applied a well known pattern-matching method, neural network analysis, to
      phenotypic data provided to participants in Genetic Analysis Workshop 14 by COGA.
      The aim is to train the network to recognize complex phenotypic patterns that are
      characteristic of those with alcoholism as well as those who are free of
      symptoms. Our results indicate that this approach may be helpful in the diagnosis
      of alcoholism. RESULTS: Training and testing of input/output pairs of risk
      factors by means of a "feed-forward back-propagation" neural network resulted in
      reliability of about 94% in predicting the presence or absence of alcoholism
      based on 36 input phenotypic risk factors. Pruning the neural network to remove
      relatively uninformative factors resulted in a reduced network of 14 input
      factors that was still 95% reliable. Some of the factors selected by the pruning
      steps have been identified as traits that show either linkage or association to
      potential candidate regions. CONCLUSION: The complex, multivariate picture formed
      by known risk factors for alcoholism can be incorporated into a neural network
      analysis that reliably predicts the presence or absence of alcoholism about 94
      95% of the time. Several characteristics that were identified by a pruned neural
      network have previously been shown to be important in this disease based on more
      traditional linkage and association studies. Neural networks therefore provide
      one less traditional approach to both identifying alcoholic individuals and
      determining the most informative risk factors.

PMID- 16451591
TI  - Boosting alternating decision trees modeling of disease trait information.
AB  - We applied the alternating decision trees (ADTrees) method to the last 3
      replicates from the Aipotu, Danacca, Karangar, and NYC populations in the Problem
      2 simulated Genetic Analysis Workshop dataset. Using information from the 12
      binary phenotypes and sex as input and Kofendrerd Personality Disorder disease
      status as the outcome of ADTrees-based classifiers, we obtained a new
      quantitative trait based on average prediction scores, which was then used for
      genome-wide quantitative trait linkage (QTL) analysis. ADTrees are machine
      learning methods that combine boosting and decision trees algorithms to generate
      smaller and easier-to-interpret classification rules. In this application, we
      compared four modeling strategies from the combinations of two boosting
      iterations (log or exponential loss functions) coupled with two choices of tree
      generation types (a full alternating decision tree or a classic boosting decision
      tree). These four different strategies were applied to the founders in each
      population to construct four classifiers, which were then applied to each study
      participant. To compute average prediction score for each subject with a specific
      trait profile, such a process was repeated with 10 runs of 10-fold cross
      validation, and standardized prediction scores obtained from the 10 runs were
      averaged and used in subsequent expectation-maximization Haseman-Elston QTL
      analyses (implemented in GENEHUNTER) with the approximate 900 SNPs in Hardy
      Weinberg equilibrium provided for each population. Our QTL analyses on the basis
      of four models (a full alternating decision tree and a classic boosting decision
      tree paired with either log or exponential loss function) detected evidence for
      linkage (Z >or= 1.96, p < 0.01) on chromosomes 1, 3, 5, and 9. Moreover, using
      average iteration and abundance scores for the 12 phenotypes and sex as their
      relevancy measurements, we found all relevant phenotypes for all four populations
      except phenotype b for the Karangar population, with suggested subgroup structure
      consistent with latent traits used in the model. In conclusion, our findings
      suggest that the ADTrees method may offer a more accurate representation of the
      disease status that allows for better detection of linkage evidence.

PMID- 16451593
TI  - Power and type I error rate of false discovery rate approaches in genome-wide
      association studies.
AB  - In genome-wide genetic studies with a large number of markers, balancing the type
      I error rate and power is a challenging issue. Recently proposed false discovery
      rate (FDR) approaches are promising solutions to this problem. Using the 100
      simulated datasets of a genome-wide marker map spaced about 3 cM and phenotypes
      from the Genetic Analysis Workshop 14, we studied the type I error rate and power
      of Storey's FDR approach, and compared it to the traditional Bonferroni
      procedure. We confirmed that Storey's FDR approach had a strong control of FDR.
      We found that Storey's FDR approach only provided weak control of family-wise
      error rate (FWER). For these simulated datasets, Storey's FDR approach only had
      slightly higher power than the Bonferroni procedure. In conclusion, Storey's FDR
      approach is more powerful than the Bonferroni procedure if strong control of FDR
      or weak control of FWER is desired. Storey's FDR approach has little power
      advantage over the Bonferroni procedure if there is low linkage disequilibrium
      among the markers. Further evaluation of the type I error rate and power of the
      FDR approaches for higher linkage disequilibrium and for haplotype analyses is
      warranted.

PMID- 16451592
TI  - Data mining of the GAW14 simulated data using rough set theory and tree-based
      methods.
AB  - Rough set theory and decision trees are data mining methods used for dealing with
      vagueness and uncertainty. They have been utilized to unearth hidden patterns in
      complicated datasets collected for industrial processes. The Genetic Analysis
      Workshop 14 simulated data were generated using a system that implemented
      multiple correlations among four consequential layers of genetic data (disease
      related loci, endophenotypes, phenotypes, and one disease trait). When
      information of one layer was blocked and uncertainty was created in the
      correlations among these layers, the correlation between the first and last
      layers (susceptibility genes and the disease trait in this case), was not easily
      directly detected. In this study, we proposed a two-stage process that applied
      rough set theory and decision trees to identify genes susceptible to the disease
      trait. During the first stage, based on phenotypes of subjects and their parents,
      decision trees were built to predict trait values. Phenotypes retained in the
      decision trees were then advanced to the second stage, where rough set theory was
      applied to discover the minimal subsets of genes associated with the disease
      trait. For comparison, decision trees were also constructed to map susceptible
      genes during the second stage. Our results showed that the decision trees of the
      first stage had accuracy rates of about 99% in predicting the disease trait. The
      decision trees and rough set theory failed to identify the true disease-related
      loci.

PMID- 16451594
TI  - A genome-wide tree- and forest-based association analysis of comorbidity of
      alcoholism and smoking.
AB  - Genetic mechanisms underlying alcoholism are complex. Understanding the etiology
      of alcohol dependence and its comorbid conditions such as smoking is important
      because of the significant health concerns. In this report, we describe a method
      based on classification trees and deterministic forests for association studies
      to perform a genome-wide joint association analysis of alcoholism and smoking.
      This approach is used to analyze the single-nucleotide polymorphism data from the
      Collaborative Study on the Genetics of Alcoholism in the Genetic Analysis
      Workshop 14. Our analysis reaffirmed the importance of sex difference in
      alcoholism. Our analysis also identified genes that were reported in other
      studies of alcoholism and identified new genes or single-nucleotide polymorphisms
      that can be useful candidates for future studies.

PMID- 16451595
TI  - Analysis of alcoholism data using support vector machines.
AB  - A supervised learning method, support vector machine, was used to analyze the
      microsatellite marker dataset of the Collaborative Study on the Genetics of
      Alcoholism Problem 1 for the Genetic Analysis Workshop 14. Twelve binary-valued
      phenotype variables were chosen for analyses using the markers from all autosomal
      chromosomes. Using various polynomial kernel functions of the support vector
      machine and randomly divided genome regions, we were able to observe the
      association of some marker sets with the chosen phenotypes and thus reduce the
      size of the dataset. The successful classifications established with the chosen
      support vector machine kernel function had high levels of correctness for each
      prediction, e.g., 96% in the fourfold cross-validations. However, owing to the
      limited sample data, we were not able to test the predictions of the classifiers
      in the new sample data.

PMID- 16451596
TI  - Use of susceptibility scoring in conjunction with the genotypic transmission
      disequilibrium test.
AB  - We explored the utility of selecting a genetically predisposed subgroup to
      increase the finding of a genetic signal in the Genetic Analysis Workshop 14
      Collaborative Study on the Genetics of Alcoholism dataset. A subgroup of affected
      probands with low environmental risk exposures was defined using a susceptibility
      score calculated from an environmental risk model. Thirty-nine probands with
      highly positive scores were selected, along with their parents, for use in a
      genotypic transmission disequilibrium test (TDT) test. We compared the results of
      the genotypic TDT in this subgroup to the TDT results using all probands and
      their parents. For some markers, the susceptibility scoring approach resulted in
      smaller p-values, while for other markers, evidence for a genetic signal
      weakened. Further explorations into genetic and environmental population
      characteristics that benefit from this approach are warranted.

PMID- 16451597
TI  - A new Bayesian approach incorporating covariate information for heterogeneity and
      its comparison with HLOD.
AB  - We consider a new Bayesian approach for heterogeneity that can take into account
      categorical covariates, if available. We use the Genetic Analysis Workshop 14
      simulated data to first compare the Bayesian approach with the heterogeneity LOD,
      when no covariate information is used. We find that the former is more powerful,
      while the two approaches have comparable false-positive rates. We then include
      informative covariates in the Bayesian approach and find that it tends to give
      more precise interval estimates of the disease gene location than when covariates
      are not included. We had knowledge of the simulation models at the time we
      performed the analyses.

PMID- 16451598
TI  - Construction of endophenotypes for complex diseases in the presence of
      heterogeneity.
AB  - Endophenotypes such as behavior disorders have been increasingly adopted in
      genetic studies for complex traits. For efficient gene mapping, it is essential
      that an endophenotype is associated with the disease of interest and is
      inheritable or co-segregating within families. In this study, we proposed a
      strategy to construct endophenotypes to analyze the Genetic Analysis Workshop 14
      simulated dataset. Initially, generalized estimating equation models were
      employed to identify phenotypes that were correlated to the disease (affected
      status) in combination with the family structures in data. Endophenotypes were
      then constructed with consideration of heterogeneity as functions of the
      identified phenotypes. Genome scans on the constructed endophenotypes were
      carried out using family-based association analysis. For comparison, genome scans
      were also performed with the original affected status. The family-based
      association analysis using the endophenotypes correctly identified the same
      susceptible gene in about 80 of the 100 replicates.

PMID- 16451599
TI  - Linkage analysis of the GAW14 simulated dataset with microsatellite and single
      nucleotide polymorphism markers in large pedigrees.
AB  - Recent studies have suggested that a high-density single nucleotide polymorphism
      (SNP) marker set could provide equivalent or even superior information compared
      with currently used microsatellite (STR) marker sets for gene mapping by linkage.
      The focus of this study was to compare results obtained from linkage analyses
      involving extended pedigrees with STR and single-nucleotide polymorphism (SNP)
      marker sets. We also wanted to compare the performance of current linkage
      programs in the presence of high marker density and extended pedigree structures.
      One replicate of the Genetic Analysis Workshop 14 (GAW14) simulated extended
      pedigrees (n = 50) from New York City was analyzed to identify the major gene D2.
      Four marker sets with varying information content and density on chromosome 3
      (STR [7.5 cM]; SNP [3 cM, 1 cM, 0.3 cM]) were analyzed to detect two traits, the
      original affection status, and a redefined trait more closely correlated with D2.
      Multipoint parametric and nonparametric linkage analyses (NPL) were performed
      using programs GENEHUNTER, MERLIN, SIMWALK2, and S.A.G.E. SIBPAL. Our results
      suggested that the densest SNP map (0.3 cM) had the greatest power to detect
      linkage for the original trait (genetic heterogeneity), with the highest LOD
      score/NPL score and mapping precision. However, no significant improvement in
      linkage signals was observed with the densest SNP map compared with STR or SNP-1
      cM maps for the redefined affection status (genetic homogeneity), possibly due to
      the extremely high information contents for all maps. Finally, our results
      suggested that each linkage program had limitations in handling the large,
      complex pedigrees as well as a high-density SNP marker set.

PMID- 16451600
TI  - Impact of the diagnosis definition on linkage detection.
AB  - Previous genome scan linkage analyses of the disease Kofendrerd Personality
      Disorder (KPD) with microsatellites led to detect some regions on chromosomes 1,
      3, 5, and 9 that were identical for the three populations AI, KA, and DA but with
      large differences in significance levels. These differences in results may be
      explained by the different diagnosis definitions depending on the
      presence/absence of 12 traits that were used in the 3 populations AI, KA, and DA.
      Heterogeneity of linkage was thus investigated here according to the
      absence/presence of each of the 12 traits in the 3 populations. For this purpose,
      two methods, the triangle test statistic and the predivided sample test were
      applied to search for genetic heterogeneity. Three regions with a strong
      heterogeneity of linkage were detected: the region on chromosome 1 according to
      the presence/absence of the traits a and b, the region on chromosome 3 for the
      trait b, and the region on chromosome 9 for the traits k and l. These 3 regions
      were the same as those detected by linkage analyses. No novel region was detected
      by the heterogeneity tests. Concerning chromosome 1, linkage analyses showed a
      much stronger evidence of linkage for traits a and b and for a combination of
      these traits than for KPD. Moreover, there was no indication of linkage to any of
      the other traits used to define the diagnosis of KPD. A genetic factor located on
      the chromosome 1 may have been detected here which would be involved specifically
      in traits a and b or in a combination of these traits.

PMID- 16451601
TI  - Performance comparison of two-point linkage methods using microsatellite markers
      flanking known disease locations.
AB  - The Genetic Analysis Workshop 14 simulated data presents an interesting,
      challenging, and plausible example of a complex disease interaction in a dataset.
      This paper summarizes the ease of detection for each of the simulated Kofendrerd
      Personality Disorder (KPD) genes across all of the replicates for five standard
      linkage statistics. Using the KPD affection status, we have analyzed the
      microsatellite markers flanking each of the disease genes, plus an additional 2
      markers that were not linked to any of the disease loci. All markers were
      analyzed using the following two-point linkage methods: 1) a MMLS, which is a
      standard admixture LOD score maximized over theta, alpha, and mode of
      inheritance, 2) a MLS calculated by GENEHUNTER, 3) the Kong and Cox LOD score as
      computed by MERLIN, 4) a MOD score (standard heterogeneity LOD maximized over
      theta, alpha, and a grid of genetic model parameters), and 5) the PPL, a Bayesian
      statistic that directly measures the strength of evidence for linkage to a
      marker. All of the major loci (D1-D4) were detectable with varying probabilities
      in the different populations. However, the modifier genes (D5 and D6) were
      difficult to detect, with similar distributions under the null and alternative
      across populations and statistics. The pooling of the four datasets in each
      replicate (n = 350 pedigrees) greatly improved the chance of detecting the major
      genes using all five methods, but failed to increase the chance to detect D5 and
      D6.

PMID- 16451602
TI  - Standard linkage and association methods identify the mechanism of four
      susceptibility genes for a simulated complex disease.
AB  - The simulated dataset of the Genetic Analysis Workshop 14 provided affection
      status and the presence or absence of 12 traits. It was determined that all
      affected individuals must have traits E, F and H (EFH phenotype) and they must
      also have either trait B (B subtype) or traits C, D, and G (CDG subtype). A
      genome screen was performed, and linkage peaks were identified on chromosomes 1,
      3, 5, and 9 using microsatellite markers. Dense panels of single-nucleotide
      polymorphism (SNP) markers were ordered for each of the four linkage peaks. In
      each case, association analyses identified a single SNP that accounted for the
      linkage evidence. The SNP on chromosome 1 appeared to primarily influence the B
      subtype, while the SNPs on chromosomes 5 and 9 primarily influenced the CDG
      subtype. The chromosome 3 SNP had the strongest effect and influenced both
      subtypes, as well as the requisite EFH phenotype. Recognizing the two subtypes
      prior to linkage analysis was key to identifying these loci using only a single
      replicate. This highlights the need in real life situations for careful
      examination of the phenotypic data prior to genetic analysis.

PMID- 16451603
TI  - Analysis of alcohol dependence phenotype in the COGA families using covariates to
      detect linkage.
AB  - Linkage analysis methods that incorporate etiological heterogeneity of complex
      diseases are likely to demonstrate greater power than traditional linkage
      analysis methods. Several such methods use covariates to discriminate between
      linked and unlinked pedigrees with respect to a certain disease locus. Here we
      apply several such methods including two mixture models, ordered subset analysis,
      and a conditional logistic model to genome scan data on the DSM-IV alcohol
      dependence phenotype on the Collaborative Studies on Genetics of Alcoholism
      families, and compare the results to traditional nonparametric linkage analysis.
      In general, there was little agreement among the various covariate-based linkage
      statistics. Linkage signals with empirical p-values less than 0.001 were detected
      on chromosomes 3, 4, 7, 10, and 12, with the highest peak occurring at the GABRB1
      gene using the ecb21 covariate.

PMID- 16451604
TI  - Methods for detecting gene x gene interaction in multiplex extended pedigrees.
AB  - Complex diseases are multifactorial in nature and can involve multiple loci with
      gene x gene and gene x environment interactions. Research on methods to uncover
      the interactions between those genes that confer susceptibility to disease has
      been extensive, but many of these methods have only been developed for sibling
      pairs or sibships. In this report, we assess the performance of two methods for
      finding gene x gene interactions that are applicable to arbitrarily sized
      pedigrees, one based on correlation in per-family nonparametric linkage scores
      and another that incorporates candidate loci genotypes as covariates into an
      affected relative pair linkage analysis. The power and type I error rate of both
      of these methods was addressed using the simulated Genetic Analysis Workshop 14
      data. In general, we found detection of the interacting loci to be a difficult
      problem, and though we experienced some modest success there is a clear need to
      continue developing new methods and approaches to the problem.

PMID- 16451605
TI  - Extension of multifactor dimensionality reduction for identifying multilocus
      effects in the GAW14 simulated data.
AB  - The multifactor dimensionality reduction (MDR) is a model-free approach that can
      identify gene x gene or gene x environment effects in a case-control study. Here
      we explore several modifications of the MDR method. We extended MDR to provide
      model selection without crossvalidation, and use a chi-square statistic as an
      alternative to prediction error (PE). We also modified the permutation test to
      provide different levels of stringency. The extended MDR (EMDR) includes three
      permutation tests (fixed, non-fixed, and omnibus) to obtain p-values of
      multilocus models. The goal of this study was to compare the different approaches
      implemented in the EMDR method and evaluate the ability to identify genetic
      effects in the Genetic Analysis Workshop 14 simulated data. We used three
      replicates from the simulated family data, generating matched pairs from family
      triads. The results showed: 1) chi-square and PE statistics give nearly
      consistent results; 2) results of EMDR without cross-validation matched that of
      EMDR with 10-fold cross-validation; 3) the fixed permutation test reports false
      positive results in data from loci unrelated to the disease, but the non-fixed
      and omnibus permutation tests perform well in preventing false positives, with
      the omnibus test being the most conservative. We conclude that the non-cross
      validation test can provide accurate results with the advantage of high
      efficiency compared to 10-cross-validation, and the non-fixed permutation test
      provides a good compromise between power and false-positive rate.

PMID- 16451607
TI  - Identifying susceptibility genes by using joint tests of association and linkage
      and accounting for epistasis.
AB  - Simulated Genetic Analysis Workshop 14 data were analyzed by jointly testing
      linkage and association and by accounting for epistasis using a candidate gene
      approach. Our group was unblinded to the "answers." The 48 single-nucleotide
      polymorphisms (SNPs) within the six disease loci were analyzed in addition to
      five SNPs from each of two non-disease-related loci. Affected sib-parent data was
      extracted from the first 10 replicates for populations Aipotu, Kaarangar, and
      Danacaa, and analyzed separately for each replicate. We developed a likelihood
      for testing association and/or linkage using data from affected sib pairs and
      their parents. Identical-by-descent (IBD) allele sharing between sibs was
      explicitly modeled using a conditional logistic regression approach and
      incorporating a covariate that represents expected IBD allele sharing given the
      genotypes of the sibs and their parents. Interactions were accounted for by
      performing likelihood ratio tests in stages determined by the highest order
      interaction term in the model. In the first stage, main effects were tested
      independently, and in subsequent stages, multilocus effects were tested
      conditional on significant marginal effects. A reduction in the number of tests
      performed was achieved by prescreening gene combinations with a goodness-of-fit
      chi square statistic that depended on mating-type frequencies. SNP-specific joint
      effects of linkage and association were identified for loci D1, D2, D3, and D4 in
      multiple replicates. The strongest effect was for SNP B03T3056, which had a
      median p-value of 1.98 x 10(-34). No two- or three-locus effects were found in
      more than one replicate.

PMID- 16451606
TI  - Multifactor-dimensionality reduction versus family-based association tests in
      detecting susceptibility loci in discordant sib-pair studies.
AB  - Complex diseases are generally thought to be under the influence of multiple, and
      possibly interacting, genes. Many association methods have been developed to
      identify susceptibility genes assuming a single-gene disease model, referred to
      as single-locus methods. Multilocus methods consider joint effects of multiple
      genes and environmental factors. One commonly used method for family-based
      association analysis is implemented in FBAT. The multifactor-dimensionality
      reduction method (MDR) is a multilocus method, which identifies multiple genetic
      loci associated with the occurrence of complex disease. Many studies of late
      onset complex diseases employ a discordant sib pairs design. We compared the FBAT
      and MDR in their ability to detect susceptibility loci using a discordant sib
      pair dataset generated from the simulated data made available to participants in
      the Genetic Analysis Workshop 14. Using FBAT, we were able to identify the effect
      of one susceptibility locus. However, the finding was not statistically
      significant. We were not able to detect any of the interactions using this
      method. This is probably because the FBAT test is designed to find loci with
      major effects, not interactions. Using MDR, the best result we obtained
      identified two interactions. However, neither of these reached a level of
      statistical significance. This is mainly due to the heterogeneity of the disease
      trait and noise in the data.

PMID- 16451608
TI  - Searching for epistatic interactions in nuclear families using conditional
      linkage analysis.
AB  - BACKGROUND: Genomic screens generally employ a single-locus strategy for linkage
      analysis, but this may have low power in the presence of epistasis. Ordered
      subsets analysis (OSA) is a method for conditional linkage analysis using
      continuous covariates. METHODS: We used OSA to evaluate two-locus interactions in
      the simulated Genetic Analysis Workshop 14 dataset. We used all nuclear families
      ascertained by Aipotu, Karangar, and Danacaa. Using the single-nucleotide
      polymorphism map, multipoint affected-sibling-pair (ASP) linkage analysis was
      performed on all 100 replicates for each chromosome using SIBLINK. OSA was used
      to examine linkage on each chromosome using LOD scores at each 3-cM location on
      every other chromosome as covariates. Two methods were used to identify positive
      results: one searching across the entire covariate chromosome, the other
      conditioning on location of known disease loci. RESULTS: Single-locus linkage
      analysis revealed very high LOD scores for disease loci D1 through D4, with mean
      LOD scores over 100 replicates ranging from 4.0 to 7.8. Although OSA did not
      obscure this linkage evidence, it did not detect the simulated interactions
      between any of the locus pairs. We found inflated type I error rates using the
      first OSA method, highlighting the need to correct for multiple comparisons.
      Therefore, using "null chromosome pairs" without simulated disease loci, we
      calculated a corrected alpha-level. CONCLUSION: We were unable to detect two
      locus interactions using OSA. This may have been due to lack of incorporation of
      phenotypic subgroups, or because linkage evidence as summarized by LOD scores
      performs poorly as an OSA covariate. We found inflated type I error rates, but
      were able to calculate a corrected alpha-level for future analyses employing this
      strategy to search for two-locus interactions.

PMID- 16451609
TI  - Analysis of genes for alcoholism using two-disease-locus models.
AB  - Using model-based two-locus methods for mapping genes, we analyzed the family
      data from the Collaborative Study on the Genetics of Alcoholism. Microsatellite
      data from 143 families ascertained through having three or more individuals
      affected with alcohol dependence were used for this investigation. Four regions
      showing evidence for linkage were identified using single-locus models from
      previous investigations. We investigated the genetic linkage, pattern of disease
      inheritance, and pair-wise genetic epistasis of these loci using the TLINKAGE
      program for two-disease-locus analysis.

PMID- 16451610
TI  - Whole-genome variance components linkage analysis using single-nucleotide
      polymorphisms versus microsatellites on quantitative traits of derived phenotypes
      from factor analysis of electroencephalogram waves.
AB  - Alcohol dependence is a serious public health problem. We studied data from
      families participating in the Collaborative Study on the Genetics of Alcoholism
      (COGA) and made available to participants in the Genetic Analysis Workshop 14
      (GAW14) in order to search for genes predisposing to alcohol dependence. Using
      factor analysis, we identified four factors (F1, F2, F3, F4) related to the
      electroencephalogram traits. We conducted variance components linkage analysis
      with each of the factors. Our results using the Affymetrix single-nucleotide
      polymorphism dataset showed significant evidence for a novel linkage of F3
      (factor comprised of the three midline channel EEG measures from the target case
      of the Visual Oddball experiment ttdt2, 3, 4) to chromosome 18 (LOD = 3.45). This
      finding was confirmed by analyses of the microsatellite data (LOD = 2.73) and
      Illumina SNP data (LOD = 3.30). We also demonstrated that, in a sample like the
      COGA data, a dense single-nucleotide polymorphism map provides better linkage
      signals than low-resolution microsatellite map with quantitative traits.

PMID- 16451611
TI  - Precision and type I error rate in the presence of genotype errors and missing
      parental data: a comparison between the original transmission disequilibrium test
      (TDT) and TDTae statistics.
AB  - BACKGROUND: Two factors impacting robustness of the original transmission
      disequilibrium test (TDT) are: i) missing parental genotypes and ii) undetected
      genotype errors. While it is known that independently these factors can inflate
      false-positive rates for the original TDT, no study has considered either the
      joint impact of these factors on false-positive rates or the precision score of
      TDT statistics regarding these factors. By precision score, we mean the absolute
      difference between disease gene position and the position of markers whose TDT
      statistic exceeds some threshold. METHODS: We apply our transmission
      disequilibrium test allowing for errors (TDTae) and the original TDT to phenotype
      and modified single-nucleotide polymorphism genotype simulation data from Genetic
      Analysis Workshop. We modify genotype data by randomly introducing genotype
      errors and removing a percentage of parental genotype data. We compute empirical
      distributions of each statistic's precision score for a chromosome harboring a
      simulated disease locus. We also consider inflation in type I error by studying
      markers on a chromosome harboring no disease locus. RESULTS: The TDTae shows
      median precision scores of approximately 13 cM, 2 cM, 0 cM, and 0 cM at the 5%,
      1%, 0.1%, and 0.01% significance levels, respectively. By contrast, the original
      TDT shows median precision scores of approximately 23 cM, 21 cM, 15 cM, and 7 cM
      at the corresponding significance levels, respectively. For null chromosomes, the
      original TDT falsely rejects the null hypothesis for 28.8%, 14.8%, 5.4%, and 1.7%
      at the 5%, 1%, 0.1% and 0.01%, significance levels, respectively, while TDTae
      maintains the correct false-positive rate. CONCLUSION: Because missing parental
      genotypes and undetected genotype errors are unknown to the investigator, but are
      expected to be increasingly prevalent in multilocus datasets, we strongly
      recommend TDTae methods as a standard procedure, particularly where stricter
      significance levels are required.

PMID- 16451612
TI  - The effect of missing data on linkage disequilibrium mapping and haplotype
      association analysis in the GAW14 simulated datasets.
AB  - We used our newly developed linkage disequilibrium (LD) plotting software, JLIN,
      to plot linkage disequilibrium between pairs of single-nucleotide polymorphisms
      (SNPs) for three chromosomes of the Genetic Analysis Workshop 14 Aipotu simulated
      population to assess the effect of missing data on LD calculations. Our haplotype
      analysis program, SIMHAP, was used to assess the effect of missing data on
      haplotype-phenotype association. Genotype data was removed at random, at levels
      of 1%, 5%, and 10%, and the LD calculations and haplotype association results for
      these levels of missingness were compared to those for the complete dataset. It
      was concluded that ignoring individuals with missing data substantially affects
      the number of regions of LD detected which, in turn, could affect tagging SNPs
      chosen to generate haplotypes.

PMID- 16451613
TI  - An analysis of identical single-nucleotide polymorphisms genotyped by two
      different platforms.
AB  - The overlap of 94 single-nucleotide polymorphisms (SNP) among the 4,720 and
      11,120 SNPs contained in the linkage panels of Illumina and Affymetrix,
      respectively, allows an assessment of the discrepancy rate produced by these two
      platforms. Although the no-call rate for the Affymetrix platform is approximately
      8.6 times greater than for the Illumina platform, when both platforms make a
      genotypic call, the agreement is an impressive 99.85%. To determine if disputed
      genotypes can be resolved without sequencing, we studied recombination in the
      region of the discrepancy for the most discrepant SNP rs958883 (typed by
      Illumina) and tsc02060848 (typed by Affymetrix). We find that the number of
      inferred recombinants is substantially higher for the Affymetrix genotypes
      compared to the Illumina genotypes. We illustrate this with pedigree 10043, in
      which 3 of 7 versus 0 of 7 offspring must be double recombinants using the
      genotypes from the Affymetrix and the Illumina platforms, respectively. Of the 36
      SNPs with one or more discrepancies, we identified a subset that appears to
      cluster in families. Some of this clustering may be due to the presence of a
      second segregating SNP that obliterates a XbaI site (the restriction enzyme used
      in the Affymetrix platform), resulting in a fragment too long (>1,000 bp) to be
      amplified.

PMID- 16451614
TI  - Effect of genotyping error in model-free linkage analysis using microsatellite or
      single-nucleotide polymorphism marker maps.
AB  - Errors while genotyping are inevitable and can reduce the power to detect
      linkage. However, does genotyping error have the same impact on linkage results
      for single-nucleotide polymorphism (SNP) and microsatellite (MS) marker maps? To
      evaluate this question we detected genotyping errors that are consistent with
      Mendelian inheritance using large changes in multipoint identity-by-descent
      sharing in neighboring markers. Only a small fraction of Mendelian consistent
      errors were detectable (e.g., 18% of MS and 2.4% of SNP genotyping errors). More
      SNP genotyping errors are Mendelian consistent compared to MS genotyping errors,
      so genotyping error may have a greater impact on linkage results using SNP marker
      maps. We also evaluated the effect of genotyping error on the power and type I
      error rate using simulated nuclear families with missing parents under 0, 0.14,
      and 2.8% genotyping error rates. In the presence of genotyping error, we found
      that the power to detect a true linkage signal was greater for SNP (75%) than MS
      (67%) marker maps, although there were also slightly more false-positive signals
      using SNP marker maps (5 compared with 3 for MS). Finally, we evaluated the
      usefulness of accounting for genotyping error in the SNP data using a likelihood
      based approach, which restores some of the power that is lost when genotyping
      error is introduced.

PMID- 16451615
TI  - Characteristics of replicated single-nucleotide polymorphism genotypes from COGA:
      Affymetrix and Center for Inherited Disease Research.
AB  - Genetic Analysis Workshop 14 provided re-genotyped single-nucleotide polymorphism
      (SNP) data. Specifically, both Center for Inherited Disease Research (CIDR) and
      Affymetrix genotyped the same 11,560 SNPs from the Affymetrix GeneChip Mapping
      10K Array marker set on the same 184 individuals from the Collaborative Study on
      the Genetics of Alcoholism database. While the inconsistency rate between CIDR
      and Affymetrix (two different genotypes for the same subject) was low (0.2%), the
      non-replication rate (two different genotypes for the same subject or one
      identified genotype and one missing genotype) was substantial (9.5%). The missing
      data could be from no-call regions, which is inconsistent with recent
      recommendations about the use of no-call regions in association tests. In
      addition, no-call regions would suggest that the actual inconsistency rate is
      higher than reported. A high inconsistency rate has significant impact on power
      in related hypothesis tests. In addition, the data are consistent with
      assumptions made in a recently proposed likelihood ratio test of association for
      re-genotyped data.

PMID- 16451616
TI  - Evaluating outlier loci and their effect on the identification of pedigree
      errors.
AB  - Homozygosity outlier loci, which show patterns of variation that are extremely
      divergent from the rest of the genome, can be evaluated by comparison of the
      homozygosity under Hardy-Weinberg proportions (the sum of the squares of allele
      frequencies) with the expected homozygosity under neutrality. Such outlier loci
      are potentially under selection (balancing selection or directional selection)
      when genome-wide effects (such as bottleneck and rapid population growth) are
      excluded. Outlier loci show skewed allele frequencies with respect to neutrality
      and may therefore affect the identification of pedigree errors. However, choosing
      neutral markers (excluding outlier loci) for the identification of pedigree
      errors has been neglected thus far. Our results showed that 4.1%, 5.5%, and 1.5%
      of the microsatellite markers, Illumina single-nucleotide polymorphisms (SNPs),
      and Affymetrix SNPs, respectively, on the autosomes appear to be under balancing
      selection (p <or= 0.01) while 0.8% of the Affymetrix SNPs are consistent with
      directional selection. On the X-chromosome, 7.7%, 3.2%, and 0.4% of the
      microsatellite markers, Illumina SNPs, and Affymetrix SNPs, respectively, appear
      to be under balancing selection. 9.3% of Illumina SNPs and 6.7% of Affymetrix
      SNPs which have high minor allele frequency (>or=40%) appear to be under
      balancing selection. Pedigree structure errors in 15 of 143 pedigrees were
      detected using microsatellite markers from the autosomes and/or selected SNPs
      from chromosomes 1 to 18 of the Illumina and/or selected SNPs from chromosomes 1
      to 16 of the Affymetrix. Outlier loci did not make a major difference to the
      identification of pedigree errors. The Collaborative Study on the Genetics of
      Alcoholism data has pedigree errors and some of them may be due to sample mix up.

PMID- 16451617
TI  - Linkage analysis of alcoholism-related electrophysiological phenotypes: genome
      scans with microsatellites compared to single-nucleotide polymorphisms.
AB  - P300 amplitude is an electrophysiological quantitative trait that is correlated
      with both alcoholism and smoking status. Using the Collaborative Study on the
      Genetics of Alcoholism data, we performed model-free linkage analysis to
      investigate the relationship between alcoholism, P300 amplitude, and habitual
      smoking. We also analyzed the effect of parent-of-origin on alcoholism, and
      utilized both microsatellites (MS) markers and single-nucleotide polymorphisms
      (SNPs). We found significant evidence of linkage for alcoholism to chromosome 10;
      inclusion of P300 amplitude as a covariate provided additional evidence of
      linkage to chromosome 12. This same region on chromosome 12 showed some evidence
      for a parent-of-origin effect. We found evidence of linkage for the P300
      phenotype to chromosome 7 in non-smokers, and to chromosome 17 in alcoholics. The
      effects of alcoholism and habitual smoking on P300 amplitude appear to have
      separate genetic determinants. Overall, there were few differences between MS and
      SNP genome scans. The use of covariates and parent-of-origin effects allowed
      detection of linkage not seen otherwise.

PMID- 16451618
TI  - X chromosome effects and their interactions with mitochondrial effects.
AB  - We report a simple and rapid method for detecting additive genetic variance due
      to X-linked loci in the absence of marker data for this chromosome. We examined
      the interaction of this method with an established method for detecting
      mitochondrial linkage (another source of sex-asymmetric genetic covariance). When
      applied to data from the Collaborative Study on the Genetics of Alcoholism, this
      method found evidence of X-chromosomal linkage for one continuous trait (ntth1)
      and one discrete trait (SPENT). Evidence of mitochondrial contribution was found
      for one discrete trait (CRAVING) and three continuous traits (ln(CIGPKYR), ecb21,
      and tth1). Results for ntth1 suggest that methods that do not also allow for male
      female heterogeneity in environmental variance may be overly conservative in
      detection of X-chromosomal effects.

PMID- 16451619
TI  - Mitochondrial genetic effects on latent class variables associated with
      susceptibility to alcoholism.
AB  - We report the results of statistical genetic analyses of data from the
      Collaborative Study on the Genetics of Alcoholism prepared for the Genetic
      Analysis Workshop 14 to detect and characterize maternally inherited
      mitochondrial genetic effects on variation in latent class psychiatric/behavioral
      variables employed in the diagnosis of alcoholism. Using published extensions to
      variance decomposition methods for statistical genetic analysis of continuous and
      discrete traits we: 1) estimated the proportion of the variance in each trait due
      to the effects of mitochondrial DNA (mtDNA), 2) tested for pleiotropy, both
      mitochondrial genetic and residual additive genetic, between trait pairs, and 3)
      evaluated whether the simultaneous estimation of mitochondrial genetic effects on
      these traits improves our ability to detect and localize quantitative trait loci
      (QTL) in the nuclear genome. After correction for multiple testing, we find
      significant (p < 0.009) mitochondrial genetic contributions to the variance for
      two latent class variables. Although we do detect significant residual additive
      genetic correlations between the two traits, there is no evidence of a residual
      mitochondrial genetic correlation between them. Evidence for autosomal QTL for
      these traits is improved when linkage screens are conditioned on significant
      mitochondrial genetic effects. We conclude that mitochondrial genes may
      contribute to variation in some latent class psychiatric/behavioral variables
      associated with alcoholism.

PMID- 16451620
TI  - A simple nonparametric multipoint procedure to test for linkage through mothers
      or fathers as well as imprinting effects in the presence of linkage.
AB  - A simple multipoint procedure to test for parent-of-origin effects in samples of
      affected siblings is discussed. The procedure consists of artificially changing
      all full sibs to half-sibs, with distinct mothers or fathers depending on the
      parental origin to be evaluated, then analyzing these families with commonly used
      statistics and software. The procedure leads to tests for linkage through mothers
      or fathers and also leads to a test for imprinting effects in the presence of
      linkage. Moreover, simulations illustrate that in regions unlinked to
      susceptibility genes this multipoint procedure does not have an inflated type I
      error if a sex-averaged genetic map is used, even when large differences exist
      between male-specific and female-specific maps. In regions linked with
      susceptibility genes, the test of imprinting is biased under the null hypothesis
      if differences exist between sex-specific maps, irrespective of the map used in
      the analysis. The procedure is applied to the Collaborative Study on the Genetics
      of Alcoholism dataset from the Genetic Analysis Workshop 14. Results indicate
      that brothers categorized as affected according to the DMS-III-R and Feighner
      classification show evidence of linkage through fathers to the 6q25 region (p =
      0.00038) as well as modest evidence of imprinting (p = 0.018). This region
      harbors OPRM1, a candidate gene for substance dependence.

PMID- 16451621
TI  - Which strategy is better for linkage analysis: single-nucleotide polymorphisms or
      microsatellites? Evaluation by identity-by-state-identity-by-descent
      transformation affected sib-pair method on GAW14 data.
AB  - The central issue for Genetic Analysis Workshop 14 (GAW14) is the question, which
      is the better strategy for linkage analysis, the use of single-nucleotide
      polymorphisms (SNPs) or microsatellite markers? To answer this question we
      analyzed the simulated data using Duffy's SIB-PAIR program, which can incorporate
      parental genotypes, and our identity-by-state - identity-by-descent (IBS-IBD)
      transformation method of affected sib-pair linkage analysis which uses the matrix
      transformation between IBS and IBD. The advantages of our method are as follows:
      the assumption of Hardy-Weinberg equilibrium is not necessary; the parental
      genotype information maybe all unknown; both IBS and its related IBD
      transformation can be used in the linkage analysis; the determinant of the IBS
      IBD transformation matrix provides a quantitative measure of the quality of the
      marker in linkage analysis. With the originally distributed simulated data, we
      found that 1) for microsatellite markers there are virtually no differences in
      types I and II error rates when parental genotypes were or were not used; 2) on
      average, a microsatellite marker has more power than a SNP marker does in linkage
      detection; 3) if parental genotype information is used, SNP markers show lower
      type I error rates than microsatellite markers; and 4) if parental genotypes are
      not available, SNP markers show considerable variation in type I error rates for
      different methods.

PMID- 16451622
TI  - A genome scan for parent-of-origin linkage effects in alcoholism.
AB  - BACKGROUND: Alcoholism is a complex disease in which genomic imprinting may play
      an important role in its susceptibility. OBJECTIVE: To conduct a genome-wide
      search for loci that may have strong parent-of-origin linkage effects in
      alcoholism; to compare the linkage results between the microsatellites and the
      two single-nucleotide polymorphism (SNP) platforms. METHODS: Nonparametric
      linkage analyses were performed using ALLEGRO with the three sets of markers
      provided by the Genetic Analysis Workshop 14 for the Collaborative Study on the
      Genetics of Alcoholism Problem 1 data. Both sex-averaged and sex-specific genetic
      maps were used. We also provided a valid statistical test to determine whether
      the parental allele sharing differed significantly. RESULTS: Significant maternal
      linkage effects (paternal imprinting) were observed on chromosome 12 using either
      the microsatellite markers or the two SNP panels. The two SNP sets did not
      improve the linkage signals compared to the results from the microsatellite
      markers on chromosome 12. Possible paternal linkage effects (maternal imprinting)
      on chromosome 7 and maternal linkage effects (paternal imprinting) on chromosome
      10 were found using the two SNP panels. CONCLUSION: For diseases which may have
      parent-of-origin effects, linkage analysis looking at parental sharing separately
      may reduce locus heterogeneity and increase the ability to identify that which
      can not be identified with usual linkage analysis.

PMID- 16451623
TI  - Genetic imprinting analysis for alcoholism genes using variance components
      approach.
AB  - Genomic imprinting, which is also known as the parent-of-origin effect, is a
      mechanism that only expresses one copy of a gene pair depending upon the parental
      origin. Although many chromosomal regions in the human genome are likely to be
      imprinted, imprinting is not accounted for in the usual linkage analysis. In this
      study, using a variance-components approach with a quantitative phenotype ttth
      FP1, we found significant evidence of imprinting at two loci, D7S1790 and
      D1S1631, on chromosome 1 and chromosome 7, respectively. Our results suggest that
      allowing for the possibility of imprinting can increase the power to detect
      linkage for localizing genes for alcoholism.

PMID- 16451624
TI  - Linkage analysis of alcohol dependence using MOD scores.
AB  - Alcohol dependence is a typical example of a complex trait that is governed by
      several genes and for which the mode of inheritance is unknown. We analyzed the
      microsatellite markers and the Affymetrix single-nucleotide polymorphisms (SNPs)
      for a subset of the Collaborative Study on the Genetics of Alcoholism family
      sample, 93 pedigrees of Caucasian ancestry comprising 919 persons, 390 of whom
      are affected according to DSM III-R and Feighner criteria. In particular, we
      performed parametric single-marker linkage analysis using MLINK of the LINKAGE
      package (for the microsatellite data), as well as multipoint MOD-score analysis
      with GENEHUNTER-MODSCORE (for the microsatellite and SNP data). By use of two
      liability classes, different penetrances were assigned to males and females. In
      order to investigate parent-of-origin effects, we calculated MOD scores under
      trait models with and without imprinting. In addition, for the microsatellite
      data, the MOD-score analysis was performed with sex-averaged as well as sex
      specific maps. The highest linkage peaks were obtained on chromosomes 1, 2, 7,
      10, 12, 13, 15, and 21. There was evidence for paternal imprinting at the loci on
      chromosomes 2, 10, 12, 13, 15, and 21. A tendency to maternal imprinting was
      observed at two loci on chromosome 7. Our findings underscore the fact that an
      adequate modeling of the genotype-phenotype relation is crucial for the genetic
      mapping of a complex trait.

PMID- 16451626
TI  - Detection of susceptibility loci by genome-wide linkage analysis.
AB  - The objective of this study is to evaluate the efficacy of a model-free linkage
      statistics for finding evidence of linkage using two different maps and to
      illustrate how the comparison of results from several populations might provide
      insight into the underlying genetic etiology of the disease of interest. The
      results obtained in terms of detection of the risk loci and threshold for
      declaring linkage and power are very similar for a dense SNP map and a sparser
      microsatellite map. The populations differed in terms of family ascertainment and
      diagnosis criteria, leading to different power to detect the individual
      underlying disease loci. Our results for the individual replicates are consistent
      with the disease model used in the simulation.

PMID- 16451625
TI  - A genome-wide linkage analysis of alcoholism on microsatellite and single
      nucleotide polymorphism data, using alcohol dependence phenotypes and
      electroencephalogram measures.
AB  - The Collaborative Study on the Genetics of Alcoholism (COGA) is a large-scale
      family study designed to identify genes that affect the risk for alcoholism and
      alcohol-related phenotypes. We performed genome-wide linkage analyses on the COGA
      data made available to participants in the Genetic Analysis Workshop 14 (GAW 14).
      The dataset comprised 1,350 participants from 143 families. The samples were
      analyzed on three technologies: microsatellites spaced at 10 cM, Affymetrix
      GeneChip Human Mapping 10 K Array (HMA10K) and Illumina SNP-based Linkage III
      Panel. We used ALDX1 and ALDX2, the COGA definitions of alcohol dependence, as
      well as electrophysiological measures TTTH1 and ECB21 to detect alcoholism
      susceptibility loci. Many chromosomal regions were found to be significant for
      each of the phenotypes at a p-value of 0.05. The most significant region for
      ALDX1 is on chromosome 7, with a maximum LOD score of 2.25 for Affymetrix SNPs,
      1.97 for Illumina SNPs, and 1.72 for microsatellites. The same regions on
      chromosome 7 (96-106 cM) and 10 (149-176 cM) were found to be significant for
      both ALDX1 and ALDX2. A region on chromosome 7 (112-153 cM) and a region on
      chromosome 6 (169-185 cM) were identified as the most significant regions for
      TTTH1 and ECB21, respectively. We also performed linkage analysis on denser maps
      of markers by combining the SNPs datasets from Affymetrix and Illumina. Adding
      the microsatellite data to the combined SNP dataset improved the results only
      marginally. The results indicated that SNPs outperform microsatellites with the
      densest marker sets performing the best.

PMID- 16451627
TI  - Linkage mapping of a complex trait in the New York population of the GAW14
      simulated dataset: a multivariate phenotype approach.
AB  - Multivariate phenotypes underlie complex traits. Thus, instead of using the end
      point trait, it may be statistically more powerful to use a multivariate
      phenotype correlated to the end-point trait for detecting linkage. In this study,
      we develop a reverse regression method to analyze linkage of Kofendrerd
      Personality Disorder affection status in the New York population of the Genetic
      Analysis Workshop 14 (GAW14) simulated dataset. When we used the multivariate
      phenotype, we obtained significant evidence of linkage near four of the six
      putative loci in at least 25% of the replicates. On the other hand, the linkage
      analysis based on Kofendrerd Personality Disorder status as a phenotype produced
      significant findings only near two of the loci and in a smaller proportion of
      replicates.

PMID- 16451629
TI  - Investigation of altering single-nucleotide polymorphism density on the power to
      detect trait loci and frequency of false positive in nonparametric linkage
      analyses of qualitative traits.
AB  - Genome-wide linkage analysis using microsatellite markers has been successful in
      the identification of numerous Mendelian and complex disease loci. The recent
      availability of high-density single-nucleotide polymorphism (SNP) maps provides a
      potentially more powerful option. Using the simulated and Collaborative Study on
      the Genetics of Alcoholism (COGA) datasets from the Genetics Analysis Workshop 14
      (GAW14), we examined how altering the density of SNP marker sets impacted the
      overall information content, the power to detect trait loci, and the number of
      false positive results. For the simulated data we used SNP maps with density of
      0.3 cM, 1 cM, 2 cM, and 3 cM. For the COGA data we combined the marker sets from
      Illumina and Affymetrix to create a map with average density of 0.25 cM and then,
      using a sub-sample of these markers, created maps with density of 0.3 cM, 0.6 cM,
      1 cM, 2 cM, and 3 cM. For each marker set, multipoint linkage analysis using
      MERLIN was performed for both dominant and recessive traits derived from marker
      loci. Our results showed that information content increased with increased map
      density. For the homogeneous, completely penetrant traits we created, there was
      only a modest difference in ability to detect trait loci. Additionally, as map
      density increased there was only a slight increase in the number of false
      positive results when there was linkage disequilibrium (LD) between markers. The
      presence of LD between markers may have led to an increased number of false
      positive regions but no clear relationship between regions of high LD and
      locations of false positive linkage signals was observed.

PMID- 16451628
TI  - Description of the data from the Collaborative Study on the Genetics of
      Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic
      Analysis Workshop 14.
AB  - The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of
      a collaboration among several different groups, catalyzed by Elizabeth Pugh from
      The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14,
      Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and
      microsatellite genomic survey were provided by the Collaborative Study on the
      Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the
      National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute
      of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing
      genes that affect the susceptibility to develop alcohol dependence and related
      phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide
      polymorphism genotyping of a large subset of the COGA subjects. This article
      briefly describes the dataset that was provided.

PMID- 16451630
TI  - Interval estimation of disease loci: development and applications of new linkage
      methods.
AB  - Three variants of the confidence set inference (CSI) procedure were proposed and
      applied to both the simulated and the Collaborative Study on the Genetics of
      Alcoholism (COGA) data. For each of the two applications, we first performed a
      preliminary genome scan study based on the microsatellite markers using the
      GENEHUNTER+ software to identify regions that potentially harbor disease loci.
      For each such region, we estimated the sibling identity-by-descent sharing
      probability distribution at the putative disease locus. Based on these estimated
      probabilities, the CSI procedures were employed to further localize the disease
      loci using the single-nucleotide polymorphism markers, leading to confidence
      intervals/regions for their locations. For our analysis with the simulated data,
      we had knowledge of the simulating models at the time we performed the analysis.

PMID- 16451631
TI  - Inclusion of unaffected sibs increases power in model-free linkage analysis of a
      behavioral trait.
AB  - Study design strategies are of critical importance in the search for genes
      underlying complex diseases. Two important design choices in planning gene
      mapping studies are the analytic strategy to be used, which will have an impact
      on the type of data to be collected, and the choice of genetic markers. In the
      present paper, we used the simulated behavioral trait data provided in the
      Genetic Analysis Workshop 14 to: 1) investigate the usefulness of incorporating
      unaffected sibs in model-free linkage analysis and, 2) compare linkage results of
      genome scans using a 7-cM microsatellite map with a 3-cM single nucleotide
      polymorphisms map. To achieve these aims, we used the maximum-likelihood-binomial
      method with two different coding approaches. We defined the unaffected sibs as
      those totally free of phenotypes correlated to the disease. Without prior
      knowledge of the answers, we were able to correctly localize 2 out of 5 loci (LOD
      > 3) in a sample of 200 families that included the unaffected sibs but only one
      locus when based on an affected-only strategy, using either microsatellite or
      SNPs genome scan. LOD scores were considerably higher using the analytic strategy
      which incorporated the unaffected sibs. In conclusion, including unaffected sibs
      in model-free linkage analysis of complex binary traits is helpful, at least when
      complete parental data are available, whereas there are no striking advantages in
      using single nucleotide polymorphisms over microsatellite map at marker densities
      used in the current study.

PMID- 16451632
TI  - Local false discovery rate and minimum total error rate approaches to identifying
      interesting chromosomal regions.
AB  - The simultaneous testing of a large number of hypotheses in a genome scan, using
      individual thresholds for significance, inherently leads to inflated genome-wide
      false positive rates. There exist various approaches to approximating the correct
      genomewide p-values under various assumptions, either by way of asymptotics or
      simulations. We explore a philosophically different criterion, recently proposed
      in the literature, which controls the false discovery rate. The test statistics
      are assumed to arise from a mixture of distributions under the null and non-null
      hypotheses. We fit the mixture distribution using both a nonparametric approach
      and commingling analysis, and then apply the local false discovery rate to select
      cut-off points for regions to be declared interesting. Another criterion, the
      minimum total error, is also explored. Both criteria seem to be sensible
      alternatives to controlling the classical type I and type II error rates.

PMID- 16451633
TI  - Resampling methods to reduce the selection bias in genetic effect estimation in
      genome-wide scans.
AB  - Using the simulated data of Problem 2 for Genetic Analysis Workshop 14 (GAW14),
      we investigated the ability of three bootstrap-based resampling estimators (a
      shrinkage, an out-of-sample, and a weighted estimator) to reduce the selection
      bias for genetic effect estimation in genome-wide linkage scans. For the given
      marker density in the preliminary genome scans (7 cM for microsatellite and 3 cM
      for SNP), we found that the two sets of markers produce comparable results in
      terms of power to detect linkage, localization accuracy, and magnitude of test
      statistic at the peak location. At the locations detected in the scan,
      application of the three bootstrap-based estimators substantially reduced the
      upward selection bias in genetic effect estimation for both true and false
      positives. The relative effectiveness of the estimators depended on the true
      genetic effect size and the inherent power to detect it. The shrinkage estimator
      is recommended when the power to detect the disease locus is low. Otherwise, the
      weighted estimator is recommended.

PMID- 16451634
TI  - Linkage and association analyses of microsatellites and single-nucleotide
      polymorphisms in nuclear families.
AB  - Several simulation studies have suggested that a high-density single-nucleotide
      polymorphisms (SNPs) marker set may be as useful as a traditional microsatellites
      (MS) marker set in performing whole-genome linkage analysis. However, very few
      studies have directly tested the SNPs-based genome-wide scan. In the present
      study, we compared the linkage results from the SNPs-based scan with a map
      density of 3-cM spacing with those from the MS scan using a 10-cM marker set
      among 300 nuclear families each from the Aipotu (AI), Danacaa (DA), and Karangar
      (KA) populations from the simulated Genetic Analysis Workshop 14 Problem 2 data.
      We found that information contents obtained from the SNPs scan were somewhat
      lower than those from the MS scan. However, the linkage results obtained from the
      two scans showed a high degree of similarity. Both scans identified a similar
      number of chromosomal regions attaining nominal significance (p < 0.05).
      Specifically, both scans detected confirmed evidence for linkage (NPL >or= 4.07,
      p = 2 x 10(-5)) to chromosome 1 in the AI families, chromosomes 1 and 3 in the DA
      families, and chromosomes 3, 5, and 9 in the KA families. An additional confirmed
      linkage to chromosome 5 in the AI families was detected only by the MS scan. We
      also observed slightly wider 1-LOD intervals for more of the SNP peaks than for
      the MS peaks, which is likely due to lower information contents for the SNPs.
      Subsequent fine-mapping association analysis further identified 2 to 3 markers
      significantly associated with disease status in each population; B03T3056,
      B03T3058, and B05T4139 in the AI population, B03T3056 and B03T3058 in the KA
      population, and B03T3056, B03T3057, and B03T3058 in the DA population. Among the
      four markers, three were chosen based on results obtained from the two scans, but
      one was solely from the SNP scan. In summary, our finding suggests that the SNP
      based genome scan has the potential to be as powerful as the traditional MS-based
      scan and offers good identification of peak location for further fine-mapped
      association analysis.

PMID- 16451635
TI  - Comparison of single-nucleotide polymorphisms and microsatellites in inference of
      population structure.
AB  - Single-nucleotide polymorphisms (SNPs) are a class of attractive genetic markers
      for population genetic studies and for identifying genetic variations underlying
      complex traits. However, the usefulness and efficiency of SNPs in comparison to
      microsatellites in different scientific contexts, e.g., population structure
      inference or association analysis, still must be systematically evaluated through
      large empirical studies. In this article, we use the Collaborative Studies on
      Genetics of Alcoholism (COGA) data from Genetic Analysis Workshop 14 (GAW14) to
      compare the performance of microsatellites and SNPs in the whole human genome in
      the context of population structure inference. A total of 328 microsatellites and
      15,840 SNPs are used to infer population structure in 236 unrelated individuals.
      We find that, on average, the informativeness of random microsatellites is four
      to twelve times that of random SNPs for various population comparisons, which is
      consistent with previous studies. Our results also indicate that for the combined
      set of microsatellites and SNPs, SNPs constitute the majority among the most
      informative markers and the use of these SNPs leads to better inference of
      population structure than the use of microsatellites. We also find that the
      inclusion of less informative markers may add noise and worsen the results.

PMID- 16451636
TI  - A comparison between microsatellite and single-nucleotide polymorphism markers
      with respect to two measures of information content.
AB  - Using the Genetic Analysis Workshop 14 (GAW14) simulated dataset, we compare
      microsatellite and single-nucleotide polymorphism (SNP) markers in terms of two
      measures of information content, the traditional entropy-based information
      content measure, and a new "relative information" measure. Both attempt to
      measure the amount of information contained in the markers about the identity-by
      descent (IBD) sharing among relatives. The performance of the two information
      measures are compared based on their variability and ability to predict change in
      the LOD score (Delta LOD) as map density increases for SNP markers. Although in a
      linked region, LOD scores are correlated with measures of information, we observe
      that none of the measures predict the LOD score itself very well. In an unlinked
      region, the LOD score is not related to either measures of information. The
      information content of microsatellite markers with 7.5-cM spacing is slightly
      higher than that of SNP markers with 3-cM spacing. At these map densities,
      microsatellites are found to be uniformly more informative than SNPs irrespective
      of their level of heterozygosity. For SNPs, we found that as the level of
      heterozygosity increases, the information content increases. As reported in all
      other previous studies, we also found that high-density SNPs have higher
      information content compared to low-density microsatellites. Performance of both
      the two information measures considered here are similar, but the relative
      information measure predicts Delta LOD as marker density increases better than
      the traditional entropy-based information measure.

PMID- 16451637
TI  - Whole-genome linkage analysis in mapping alcoholism genes using single-nucleotide
      polymorphisms and microsatellites.
AB  - There is currently a great interest in using single-nucleotide polymorphisms
      (SNPs) in genetic linkage and association studies because of the abundance of
      SNPs as well as the availability of high-throughput genotyping technologies. In
      this study, we compared the performance of whole-genome scans using SNPs with
      microsatellites on 143 pedigrees from the Collaborative Studies on Genetics of
      Alcoholism provided by Genetic Analysis Workshop 14. A total of 315
      microsatellites and 10,081 SNPs from Affymetrix on 22 autosomal chromosomes were
      used in our analyses. We found that the results from the two scans had good
      overall concordance. One region on chromosome 2 and two regions on chromosome 7
      showed significant linkage signals (i.e., NPL >or= 2) for alcoholism from both
      the SNP and microsatellite scans. The different results observed between the two
      scans may be explained by the difference observed in information content between
      the SNPs and the microsatellites.

PMID- 16451638
TI  - Comparison of microsatellites, single-nucleotide polymorphisms (SNPs) and
      composite markers derived from SNPs in linkage analysis.
AB  - There is growing evidence that a map of dense single-nucleotide polymorphisms
      (SNPs) can outperform a map of sparse microsatellites for linkage analysis. There
      is also argument as to whether a clustered SNP map can outperform an evenly
      spaced SNP map. Using Genetic Analysis Workshop 14 simulated data, we compared
      for linkage analysis microsatellites, SNPs, and composite markers derived from
      SNPs. We encoded the composite markers in a two-step approach, in which the
      maximum identity length contrast method was employed to allow for recombination
      between loci. A SNP map 2.3 times as dense as a microsatellite map (approximately
      2.9 cM compared to approximately 6.7 cM apart) provided slightly less information
      content (approximately 0.83 compared to approximately 0.89). Most inheritance
      information could be extracted when the SNPs were spaced < 1 cM apart. Comparing
      the linkage results on using SNPs or composite markers derived from them based on
      both 3 cM and 0.3 cM resolution maps, we showed that the inter-SNP distance
      should be kept small (< 1 cM), and that for multipoint linkage analysis the
      original markers and the derived composite markers had similar power; but for
      single point linkage analysis the resulting composite markers lead to more power.
      Considering all factors, such as information content, flexibility of analysis
      method, map errors, and genotyping errors, a map of clustered SNPs can be an
      efficient design for a genome-wide linkage scan.

PMID- 16451639
TI  - Construction of the model for the Genetic Analysis Workshop 14 simulated data:
      genotype-phenotype relationships, gene interaction, linkage, association,
      disequilibrium, and ascertainment effects for a complex phenotype.
AB  - The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the
      ability to find genes related to a complex disease (such as alcoholism). Such a
      disease may be given a variety of definitions by different investigators, have
      associated endophenotypes that are common in the general population, and is
      likely to be not one disease but a heterogeneous collection of clinically
      similar, but genetically distinct, entities. 2) To observe the effect on genetic
      analysis and gene discovery of a complex set of gene x gene interactions. 3) To
      allow comparison of microsatellite vs. large-scale single-nucleotide polymorphism
      (SNP) data. 4) To allow testing of association to identify the disease gene and
      the effect of moderate marker x marker linkage disequilibrium. 5) To observe the
      effect of different ascertainment/disease definition schemes on the analysis.
      Data was distributed in two forms. Data distributed to participants contained
      about 1,000 SNPs and 400 microsatellite markers. Internet-obtainable data
      consisted of a finer 10,000 SNP map, which also contained data on controls. While
      disease characteristics and parameters were constant, four "studies" used varying
      ascertainment schemes based on differing beliefs about disease characteristics.
      One of the studies contained multiplex two- and three-generation pedigrees with
      at least four affected members. The simulated disease was a psychiatric condition
      with many associated behaviors (endophenotypes), almost all of which were genetic
      in origin. The underlying disease model contained four major genes and two
      modifier genes. The four major genes interacted with each other to produce three
      different phenotypes, which were themselves heterogeneous. The population
      parameters were calibrated so that the major genes could be discovered by linkage
      analysis in most datasets. The association evidence was more difficult to
      calibrate but was designed to find statistically significant association in 50%
      of datasets. We also simulated some marker x marker linkage disequilibrium around
      some of the genes and also in areas without disease genes. We tried two different
      methods to simulate the linkage disequilibrium.

PMID- 16451640
TI  - A genome-wide scanning and fine mapping study of COGA data.
AB  - A thorough genetic mapping study was performed to identify predisposing genes for
      alcoholism dependence using the Collaborative Study on the Genetics of Alcoholism
      (COGA) data. The procedure comprised whole-genome linkage and confirmation
      analyses, single locus and haplotype fine mapping analyses, and gene x
      environment haplotype regression. Stratified analysis was considered to reduce
      the ethnic heterogeneity and simultaneously family-based and case-control study
      designs were applied to detect potential genetic signals. By using different
      methods and markers, we found high linkage signals at D1S225 (253.7 cM), D1S547
      (279.2 cM), D2S1356 (64.6 cM), and D7S2846 (56.8 cM) with nonparametric linkage
      scores of 3.92, 4.10, 4.44, and 3.55, respectively. We also conducted haplotype
      and odds ratio analyses, where the response was the dichotomous status of alcohol
      dependence, explanatory variables were the inferred individual haplotypes and the
      three statistically significant covariates were age, gender, and max drink (the
      maximum number of drinks consumed in a 24-hr period). The final model identified
      important AD-related haplotypes within a candidate region of NRXN1 at 2p21 and a
      few others in the inter-gene regions. The relative magnitude of risks to the
      identified risky/protective haplotypes was elucidated.

PMID- 16451641
TI  - Linkage analysis and association analysis in the presence of linkage using age at
      onset of COGA alcoholism data.
AB  - Complex disease mapping usually involves a combination of linkage and association
      techniques. Linkage analysis can scan the entire genome in a few hundred tests.
      Association tests may involve an even greater number of tests. However,
      association tests can localize the susceptibility genes more accurately. Using a
      recently developed combined linkage and association strategy, we analyzed a
      subset of the Collaborative Study on the Genetics of Alcoholism (COGA) data for
      the Genetic Analysis Workshop 14 (GAW14). In this analysis, we first employed
      linkage analysis based on frailty models that take into account age of onset
      information to establish which regions along the chromosome are likely to harbor
      disease susceptibility genes for alcohol dependence. Second, we used an
      association analysis by exploiting linkage disequilibrium to narrow down the peak
      regions. We also compare the methods with mean identity-by-descent tests and
      transmission/disequilibrium tests that do not use age of onset information.

PMID- 16451642
TI  - Single-nucleotide polymorphism versus microsatellite markers in a combined
      linkage and segregation analysis of a quantitative trait.
AB  - Increasingly, single-nucleotide polymorphism (SNP) markers are being used in
      preference to microsatellite markers. However, methods developed for
      microsatellites may be problematic when applied to SNP markers. We evaluated the
      results of using SNPs vs. microsatellites in Monte Carlo Markov chain (MCMC)
      oligogenic combined segregation and linkage analysis methods. These methods were
      developed with microsatellite markers in mind. We selected chromosome 7 from the
      Collaborative Study on the Genetics of Alcoholism dataset for analysis because
      linkage to an electrophysiological trait had been reported there. We found
      linkage in the same region of chromosome 7 with the Affymetrix SNP data, the
      Illumina SNP data, and the microsatellite marker data. The MCMC sampler appears
      to mix with both types of data. The sampler implemented in this MCMC oligogenic
      combined segregation and linkage analysis appears to handle SNP data as well as
      microsatellite data and it is possible that the localizations with the SNP data
      are better.

PMID- 16451643
TI  - Application of the propensity score in a covariate-based linkage analysis of the
      Collaborative Study on the Genetics of Alcoholism.
AB  - BACKGROUND: Covariate-based linkage analyses using a conditional logistic model
      as implemented in LODPAL can increase the power to detect linkage by minimizing
      disease heterogeneity. However, each additional covariate analyzed will increase
      the degrees of freedom for the linkage test, and therefore can also increase the
      type I error rate. Use of a propensity score (PS) has been shown to improve
      consistently the statistical power to detect linkage in simulation studies.
      Defined as the conditional probability of being affected given the observed
      covariate data, the PS collapses multiple covariates into a single variable. This
      study evaluates the performance of the PS to detect linkage evidence in a genome
      wide linkage analysis of microsatellite marker data from the Collaborative Study
      on the Genetics of Alcoholism. Analytical methods included nonparametric linkage
      analysis without covariates, with one covariate at a time including multiple PS
      definitions, and with multiple covariates simultaneously that corresponded to the
      PS definitions. Several definitions of the PS were calculated, each with
      increasing number of covariates up to a maximum of five. To account for the
      potential inflation in the type I error rates, permutation based p-values were
      calculated. RESULTS: Results suggest that the use of individual covariates may
      not necessarily increase the power to detect linkage. However the use of a PS can
      lead to an increase when compared to using all covariates simultaneously.
      Specifically, PS3, which combines age at interview, sex, and smoking status,
      resulted in the greatest number of significant markers identified. All methods
      consistently identified several chromosomal regions as significant, including
      loci on chromosome 2, 6, 7, and 12. CONCLUSION: These results suggest that the
      use of a propensity score can increase the power to detect linkage for a complex
      disease such as alcoholism, especially when multiple important covariates can be
      used to predict risk and thereby minimize linkage heterogeneity. However, because
      the PS is calculated as a conditional probability of being affected, it does
      require the presence of observed covariate data on both affected and unaffected
      individuals, which may not always be available in real data sets.

PMID- 16451644
TI  - Multipoint identity-by-descent computations for single-point polymorphism and
      microsatellite maps.
AB  - We used the LOKI software to generate multipoint identity-by-descent matrices for
      a microsatellite map (with 31 markers) and two single-nucleotide polymorphism
      (SNP) maps to examine information content across chromosome 7 in the
      Collaborative Study on the Genetics of Alcoholism dataset. Despite the lower
      information provided by a single SNP, SNP maps overall had higher and more
      uniform information content across the chromosome. The Affymetrix map (578 SNPs)
      and the Illumina map (271 SNPs) provided almost identical information. However,
      increased information has a computational cost: SNP maps require 100 times as
      many iterations as microsatellites to produce stable estimates.

PMID- 16451645
TI  - Simulation-based homozygosity mapping with the GAW14 COGA dataset on alcoholism.
AB  - BACKGROUND: We have developed a simulation-based approach to the analysis of
      shared homozygous chromosomal segments and have applied it to data on allele
      sharing among alcoholics in a single Collaborative Study on the Genetics of
      Alcoholism pedigree. Our assessment of sharing involved the use of a single
      nucleotide polymorphism (SNP) marker map provided by Affymetrix. RESULTS: All 11
      affected individuals in the selected pedigree shared 2 copies of an allele at 4
      adjacent SNPs in a region on chromosome 5. Via simulation, we determined that the
      probability that such sharing is caused by mere chance is less than 0.0000001.
      After correcting for undocumented inbreeding, this probability rose to 0.0016.
      The probability that the shared segment emanates from a single ancestor and is
      unrelated to the affection status is less than 0.0000001 in the corrected
      pedigree. Haplotype association analysis and a search for a protective locus
      using unaffected individuals yielded no significant results. CONCLUSION:
      Homozygosity mapping results on chromosome 5 provide suggestive evidence of the
      region's role as one that may harbor a genetic determinant of alcoholism.
      Furthermore, the probabilities of chance homozygous allele sharing for the
      original and for the inbreeding-corrected pedigree provide insight into the
      impact that inbreeding can have on such calculations.

PMID- 16451646
TI  - Linkage analysis of alcohol dependence using both affected and discordant sib
      pairs.
AB  - The basic idea of affected-sib-pair (ASP) linkage analysis is to test whether the
      inheritance pattern of a marker deviates from Mendelian expectation in a sample
      of ASPs. The test depends on an assumed Mendelian control distribution of the
      number of marker alleles shared identical by descent (IBD), i.e., 1/4, 1/2, and
      1/4 for 2, 1, and 0 allele(s) IBD, respectively. However, Mendelian transmission
      may not always hold, for example because of inbreeding or meiotic drive at the
      marker or a nearby locus. A more robust and valid approach is to incorporate
      discordant-sib-pairs (DSPs) as controls to avoid possible false-positive results.
      To be robust to deviation from Mendelian transmission, here we analyzed
      Collaborative Study on the Genetics of Alcoholism data by modifying the ASP LOD
      score method to contrast the estimated distribution of the number of allele(s)
      shared IBD by ASPs with that by DSPs, instead of with the expected distribution
      under the Mendelian assumption. This strategy assesses the difference in IBD
      sharing between ASPs and the IBD sharing between DSPs. Further, it works better
      than the conventional LOD score ASP linkage method in these data in the sense of
      avoiding false-positive linkage evidence.

PMID- 16451647
TI  - Multilocus and interaction-based genome scan for alcoholism risk factors in
      Caucasian Americans: the COGA study.
AB  - In this paper, we applied the nonparametric linkage regression approach to the
      Caucasian genome scan data from the Collaborative Study on the Genetics of
      Alcoholism to search for regions of the genome that exhibit evidence for linkage
      to putative alcoholism-predisposing genes. The multipoint single-locus model
      identified four regions of the genome with LOD scores greater than one. These
      regions were on 7p near D7S1790 (LOD = 1.31), two regions on 7q near D7S1870 (LOD
      = 1.15) and D7S1799 (LOD = 1.13) and 21q near D21S1440 and D21S1446 (LOD = 1.78).
      Jointly modeling these loci provided stronger evidence for linkage in each of
      these regions (LOD = 1.58 on 7q11, LOD = 1.61 on 11q23, and LOD = 1.95 on 21q22).
      The evidence for linkage tended to increase among pedigrees with earlier mean age
      of onset at 8q23 (p = 0.0016), 14q21 (p = 0.0079), and 18p12 (p = 0.0021) and
      with later mean age of onset at 4q35 (p = 0.0067) and 9p22 (p = 0.0008).

PMID- 16451648
TI  - Recursive partitioning models for linkage in COGA data.
AB  - We have developed a recursive-partitioning (RP) algorithm for identifying
      phenotype and covariate groupings that interact with the evidence for linkage.
      This data-mining approach for detecting gene x environment interactions uses
      genotype and covariate data on affected relative pairs to find evidence for
      linkage heterogeneity across covariate-defined subgroups. We adapted a likelihood
      ratio based test of linkage parameterized with relative risks to a recursive
      partitioning framework, including a cross-validation based deviance measurement
      for choosing optimal tree size and a bootstrap sampling procedure for choosing
      robust tree structure. ALDX2 category 5 individuals were considered affected,
      categories 1 and 3 unaffected, and all others unknown. We sampled non-overlapping
      affected relative pairs from each family; therefore, we used 144 affected pairs
      in the RP model. Twenty pair-level covariates were defined from smoking status,
      maximum drinks, ethnicity, sex, and age at onset. Using the all-pairs score in
      GENEHUNTER, the nonparametric linkage tests showed no regions with suggestive
      linkage evidence. However, using the RP model, several suggestive regions were
      found on chromosomes 2, 4, 6, 14, and 20, with detection of associated covariates
      such as sex and age at onset.

PMID- 16451649
TI  - A Bayesian approach for applying Haseman-Elston methods.
AB  - The main goal of this paper is to couple the Haseman-Elston method with a simple
      yet effective Bayesian factor-screening approach. This approach selects markers
      by considering a set of multigenic models that include epistasis effects. The
      markers are ranked based on their marginal posterior probability. A significant
      improvement over our previously proposed Bayesian variable selection methodology
      is a simple Metropolis-Hasting algorithm that requires minimum tuning on the
      prior settings. The algorithm, however, is also flexible enough for us to easily
      incorporate our hypotheses and avoid computational pitfalls. We apply our
      approach to the microsatellite data of Collaborative Studies on Genetics of
      Alcoholism using the coded values for the ALDX1 variable as our response.

PMID- 16451650
TI  - Genome scan linkage analysis comparing microsatellites and single-nucleotide
      polymorphisms markers for two measures of alcoholism in chromosomes 1, 4, and 7.
AB  - BACKGROUND: We analyzed 143 pedigrees (364 nuclear families) in the Collaborative
      Study on the Genetics of Alcoholism (COGA) data provided to the participants in
      the Genetic Analysis Workshop 14 (GAW14) with the goal of comparing results
      obtained from genome linkage analysis using microsatellite and with results
      obtained using SNP markers for two measures of alcoholism (maximum number of
      drinks -MAXDRINK and an electrophysiological measure from EEG -TTTH1). First, we
      constructed haplotype blocks by using the entire set of single-nucleotide
      polymorphisms (SNP) in chromosomes 1, 4, and 7. These chromosomes have shown
      linkage signals for MAXDRINK or EEG-TTTH1 in previous reports. Second, we
      randomly selected one, two, three, four, and five SNPs from each block (referred
      to as Rep1 - Rep5, respectively) to conduct linkage analysis using variance
      component approach. Finally, results of all SNP analyses were compared with those
      obtained using microsatellite markers. RESULTS: The LOD scores obtained from SNPs
      were slightly higher but the curves were not radically different from those
      obtained from microsatellite analyses. The peaks of linkage regions from SNP sets
      were slightly shifted to the left when compared to those from microsatellite
      markers. The reduced sets of SNPs provide signals in the same linkage regions but
      with a smaller LOD score suggesting a significant impact of the decrease in
      information content on linkage results. The widths of 1 LOD support interval of
      linkage regions from SNP sets were smaller when compared to those of
      microsatellite markers. However, two linkage regions obtained from the
      microsatellite linkage analysis on chromosome 7 for LOG of TTTH1 were not
      detected in the SNP based analyses. CONCLUSION: The linkage results from SNPs
      showed narrower linkage regions and slightly higher LOD scores when compared to
      those of microsatellite markers. The different builds of the genetic maps used in
      microsatellite and SNPs markers or/and errors in genotyping may account for the
      microsatellite linkage signals on chromosome 7 that were not identified using
      SNPs. Also, unresolved map issues between SNPs and microsatellite markers may be
      partly responsible for the shifted linkage peaks when comparing the two types of
      markers.

PMID- 16451651
TI  - Linkage analysis of GAW14 simulated data: comparison of multimarker, multipoint,
      and conditional approaches.
AB  - The purposes of this study were 1) to examine the performance of a new
      multimarker regression approach for model-free linkage analysis in comparison to
      a conventional multipoint approach, and 2) to determine the whether a
      conditioning strategy would improve the performance of the conventional
      multipoint method when applied to data from two interacting loci. Linkage
      analysis of the Kofendrerd Personality Disorder phenotype to chromosomes 1 and 3
      was performed in three populations for all 100 replicates of the Genetic Analysis
      Workshop 14 simulated data. Three approaches were used: a conventional multipoint
      analysis using the Zlr statistic as calculated in the program ALLEGRO; a
      conditioning approach in which the per-family contribution on one chromosome was
      weighted according to evidence for linkage on the other chromosome; and a novel
      multimarker regression approach. The multipoint and multimarker approaches were
      generally successful in localizing known susceptibility loci on chromosomes 1 and
      3, and were found to give broadly similar results. No advantage was found with
      the per-family conditioning approach. The effect on power and type I error of
      different choices of weighting scheme (to account for different numbers of
      affected siblings) in the multimarker approach was examined.

PMID- 16451652
TI  - Genome-wide linkage and association mapping of disease genes with the GAW14
      simulated datasets.
AB  - We combined the results of whole-genome linkage and association analyses to
      determine which markers were most strongly associated with Kofendrerd Personality
      Disorder. Using replicate 1 from the Genetic Analysis Workshop 14 Aipotu,
      Karangar, Danacaa, and New York City simulated populations, we determined that
      several markers showed significant linkage and association with disease status.
      We used both SNP and microsatellite markers to determine patterns and chromosomal
      regions of markers. Three consistently associated markers were C01R0050,
      C03R0280, and C10R0882. Using generalized linear mixed models, we modelled the
      effect of the three predefined phenotypic categories on disease status and
      concluded that the phenotypes defining the "anxiety-related" category best
      predicted the outcome.

PMID- 16451653
TI  - Identifying genomic regions for fine-mapping using genome scan meta-analysis
      (GSMA) to identify the minimum regions of maximum significance (MRMS) across
      populations.
AB  - In order to detect linkage of the simulated complex disease Kofendrerd
      Personality Disorder across studies from multiple populations, we performed a
      genome scan meta-analysis (GSMA). Using the 7-cM microsatellite map,
      nonparametric multipoint linkage analyses were performed separately on each of
      the four simulated populations independently to determine p-values. The genome of
      each population was divided into 20-cM bin regions, and each bin was rank-ordered
      based on the most significant linkage p-value for that population in that region.
      The bin ranks were then averaged across all four studies to determine the most
      significant 20-cM regions over all studies. Statistical significance of the
      averaged bin ranks was determined from a normal distribution of randomly assigned
      rank averages. To narrow the region of interest for fine-mapping, the meta
      analysis was repeated two additional times, with each of the 20-cM bins offset by
      7 cM and 13 cM, respectively, creating regions of overlap with the original
      method. The 6-7 cM shared regions, where the highest averaged 20-cM bins from
      each of the three offsets overlap, designated the minimum region of maximum
      significance (MRMS). Application of the GSMA-MRMS method revealed genome wide
      significance (p-values refer to the average rank assigned to the bin) at regions
      including or adjacent to all of the simulated disease loci: chromosome 1 (p <
      0.0001 for 160-167 cM, including D1), chromosome 3 (p-value < 0.0000001 for 287
      294 cM, including D2), chromosome 5 (p-value < 0.001 for 0-7 cM, including D3),
      and chromosome 9 (p-value < 0.05 for 7-14 cM, the region adjacent to D4). This
      GSMA analysis approach demonstrates the power of linkage meta-analysis to detect
      multiple genes simultaneously for a complex disorder. The MRMS method enhances
      this powerful tool to focus on more localized regions of linkage.

PMID- 16451654
TI  - An updated meta-analysis approach for genetic linkage.
AB  - We present a meta-analysis procedure for genome-wide linkage studies (MAGS). The
      MAGS procedure combines genome-wide linkage results across studies with possibly
      distinct marker maps. We applied the MAGS procedure to the simulated data from
      the Genetic Analysis Workshop 14 in order to investigate power to detect linkage
      to disease genes and power to detect linkage to disease modifier genes while
      controlling for type I error. We analyzed all 100 replicates of the four
      simulated studies for chromosomes 1 (disease gene), 2 (modifier gene), 3 (disease
      gene), 4 (no disease gene), 5 (disease gene), and 10 (modifier gene) with
      knowledge of the simulated disease gene locations. We found that the procedure
      correctly identified the disease loci on chromosomes 1, 3, and 5 and did not
      erroneously identify a linkage signal on chromosome 4. The MAGS procedure
      provided little to no evidence of linkage to the disease modifier genes on
      chromosomes 2 and 10.

PMID- 16451655
TI  - Calculation of multipoint likelihoods using flanking marker data: a simulation
      study.
AB  - The calculation of multipoint likelihoods is computationally challenging, with
      the exact calculation of multipoint probabilities only possible on small
      pedigrees with many markers or large pedigrees with few markers. This paper
      explores the utility of calculating multipoint likelihoods using data on markers
      flanking a hypothesized position of the trait locus. The calculation of such
      likelihoods is often feasible, even on large pedigrees with missing data and
      complex structures. Performance characteristics of the flanking marker procedure
      are assessed through the calculation of multipoint heterogeneity LOD scores on
      data simulated for Genetic Analysis Workshop 14 (GAW14). Analysis is restricted
      to data on the Aipotu population on chromosomes 1, 3, and 4, where chromosomes 1
      and 3 are known to contain disease loci. The flanking marker procedure performs
      well, even when missing data and genotyping errors are introduced.

PMID- 16451657
TI  - Modeling the effect of an associated single-nucleotide polymorphism in linkage
      studies.
AB  - For linkage analysis in affected sibling pairs, we propose a regression model to
      incorporate information from a disease-associated single-nucleotide polymorphism
      located under the linkage peak. This model can be used to study if the associated
      single-nucleotide polymorphism marker partly explains the original linkage peak.
      Two sources of information are used for performing this task, namely the
      genotypes of the parents and the genotypes of the siblings. We applied the
      methods to three significantly disease-associated single-nucleotide polymorphisms
      and five microsatellite markers at the end of chromosome 3 of replicate 1 of
      Aipotu population. Two out of five of the microsatellite markers showed a LOD
      score higher than 3. The question to be answered was whether one of the single
      nucleotide polymorphisms partly explains these high LOD scores. We did not have
      the answers when we analyzed the data.

PMID- 16451656
TI  - Covariate linkage analysis of GAW14 simulated data incorporating subclinical
      phenotype, sex, population, parent-of-origin, and interaction.
AB  - BACKGROUND: We evaluate a method for the incorporation of covariates into linkage
      analysis using the Genetic Analysis Workshop 14 simulated data. Focusing on a
      randomly chosen replicate (42) we investigated the effect of the 12 subclinical
      phenotypes, sex, population, and parent-of-origin on the linkage signal from a
      model-free linkage analysis of Kofendrerd Personality Disorder. RESULTS: We
      detected a linkage peak on chromosome 1, at about 175 cM, which varied depending
      upon individuals' status for subclinical phenotype b. A linkage peak on
      chromosome 3 (310 cM) was found not to depend upon subclinical phenotype status.
      Further peaks were found on chromosomes 5 (12 cM), 9 (4 cM), and 10 (95 cM),
      depending on the status of subclinical phenotypes a, k, and c/d/g, respectively.
      CONCLUSION: Retrospective comparison of our results with the simulation model
      showed correct identification of disease loci D1-5 on chromosomes 1, 3, 5, 9 and
      10, respectively.

PMID- 16451658
TI  - A gene-model-free method for linkage analysis of a disease-related-trait based on
      analysis of proband/sibling pairs.
AB  - In this paper we investigate the power of finding linkage to a disease locus
      through analysis of the disease-related traits. We propose two family-based gene
      model-free linkage statistics. Both involve considering the distribution of the
      number of alleles identical by descent with the proband and comparing siblings
      with the disease-related trait to those without the disease-related-trait. The
      objective is to find linkages to disease-related traits that are pleiotropic for
      both the disease and the disease-related-traits. The power of these statistics is
      investigated for Kofendrerd Personality Disorder-related traits a
      (Joining/founding cults) and trait b (Fear/discomfort with strangers) of the
      simulated data. The answers were known prior to the execution of the reported
      analyses. We find that both tests have very high power when applied to the
      samples created by combining the data of the three cities for which we have
      nuclear family data.

PMID- 16451659
TI  - The role of parametric linkage methods in complex trait analyses using
      microsatellites.
AB  - Many investigators of complexly inherited familial traits bypass classical
      segregation analysis to perform model-free genome-wide linkage scans. Because
      model-based or parametric linkage analysis may be the most powerful means to
      localize genes when a model can be approximated, model-free statistics may result
      in a loss of power to detect linkage. We performed limited segregation analyses
      on the electrophysiological measurements that have been collected for the
      Collaborative Study on the Genetics of Alcoholism. The resulting models are used
      in whole-genome scans. Four genomic regions provided a model-based LOD > 2 and
      only 3 of these were detected (p < 0.05) by a model-free approach. We conclude
      that parametric methods, using even over-simplified models of complex phenotypes,
      may complement nonparametric methods and decrease false positives.

PMID- 16451660
TI  - Including endophenotypes as covariates in variance component heritability and
      linkage analysis.
AB  - The purpose of these analyses was to determine if incorporating or adjusting for
      covariates in genetic analyses helped or hindered in genetic analyses,
      specifically heritability and linkage analyses. To study this question, two types
      of covariate models were used in the simulated Genetic Analysis Workshop 14
      dataset in which the true gene locations are known. All four populations of one
      replicate were combined for the analyses. The first model included typical
      covariates of sex and cohort (population) and the second included the typical
      covariates and also those related endophenotypes that are thought to be
      associated with the trait (phenotypes A, B, C, D, E, F, G, H, I, J, K, and L). A
      final best fit model produced in the heritability analyses was used for linkage.
      Linkage for disease genes D1, D3, and D4 were localized using models with and
      without the covariates. The use of inclusion of covariates did not appear to have
      any consistent advantage or disadvantage for the different phenotypes in regards
      to gene localization or false positive rate.

PMID- 16451661
TI  - Comparison of single-nucleotide polymorphisms and microsatellites in detecting
      quantitative trait loci for alcoholism: the Collaborative Study on the Genetics
      of Alcoholism.
AB  - BACKGROUND: The feasibility of effectively analyzing high-density single
      nucleotide polymorphism (SNP) maps in whole genome scans of complex traits is not
      known. The purpose of this study was to compare variance components linkage
      results using different density marker maps in data from the Collaborative Study
      on the Genetics of Alcoholism (COGA). Marker maps having an average spacing of 10
      cM (microsatellite), 0.78 cM (SNP1), and 0.31 cM (SNP2) were used to identify
      quantitative trait loci (QTLs) affecting maximum number of alcoholic drinks
      consumed in a 24-hour period (Inmaxalc). RESULTS: Heritability of Inmaxalc was
      estimated to be 15%. Multipoint variance components linkage analysis revealed
      similar linkage patterns among the three marker panels, with the SNP maps
      consistently yielding higher LOD scores. Robust LOD scores > 1.0 were observed on
      chromosomes 1 and 13 for all three marker maps. Additional LODs > 1.0 were
      observed on chromosome 4 with both SNP maps and on chromosomes 18 and 21 with the
      SNP2 map. Peak LOD scores for Inmaxalc were observed on chromosome 1, although
      none reached genome-wide statistical significance. Quantile-quantile plots
      revealed that the multipoint distribution of SNP results appeared to fit the
      asymptotic null distribution better than the twopoint results. CONCLUSION: In
      conclusion, variance-components linkage analysis using high-density SNP maps
      provided higher LOD scores compared with the standard microsatellite map, similar
      to studies using nonparametric linkage methods. Widespread application of SNP
      maps will depend on further improvements in the computational methods implemented
      in current software packages.

PMID- 16451662
TI  - Haseman-Elston weighted by marker informativity.
AB  - In the Haseman-Elston approach the squared phenotypic difference is regressed on
      the proportion of alleles shared identical by descent (IBD) to map a quantitative
      trait to a genetic marker. In applications the IBD distribution is estimated and
      usually cannot be determined uniquely owing to incomplete marker information. At
      Genetic Analysis Workshop (GAW) 13, Jacobs et al. [BMC Genet 2003, 4(Suppl
      1):S82] proposed to improve the power of the Haseman-Elston algorithm by
      weighting for information available from marker genotypes. The authors did not
      show, however, the validity of the employed asymptotic distribution. In this
      paper, we use the simulated data provided for GAW 14 and show that weighting
      Haseman-Elston by marker information results in increased type I error rates.
      Specifically, we demonstrate that the number of significant findings throughout
      the chromosome is significantly increased with weighting schemes. Furthermore, we
      show that the classical Haseman-Elston method keeps its nominal significance
      level when applied to the same data. We therefore recommend to use Haseman-Elston
      with marker informativity weights only in conjunction with empirical p-values.
      Whether this approach in fact yields an increase in power needs to be
      investigated further.

PMID- 16451663
TI  - Whole-genome association analysis to identify markers associated with
      recombination rates using single-nucleotide polymorphisms and microsatellites.
AB  - Recombination during meiosis is one of the most important biological processes,
      and the level of recombination rates for a given individual is under genetic
      control. In this study, we conducted genome-wide association studies to identify
      chromosomal regions associated with recombination rates. We analyzed genotype
      data collected on the pedigrees in the Collaborative Study on the Genetics on
      Alcoholism data provided by Genetic Analysis Workshop 14. A total of 315
      microsatellites and 10,081 single-nucleotide polymorphisms from Affymetrix on 22
      autosomal chromosomes were used in our association analysis. Genome-wide gender
      specific recombination counts for family founders were inferred first and
      association analysis was performed using multiple linear regressions. We used the
      positive false discovery rate (pFDR) to account for multiple comparisons in the
      two genome-wide scans. Eight regions showed some evidence of association with
      recombination counts based on the single-nucleotide polymorphism analysis after
      adjusting for multiple comparisons. However, no region was found to be
      significant using microsatellites.

PMID- 16451664
TI  - On normality, ethnicity, and missing values in quantitative trait locus mapping.
AB  - BACKGROUND: This paper deals with the detection of significant linkage for
      quantitative traits using a variance components approach. Microsatellite markers
      were obtained for the Genetic Analysis Workshop 14 Collaborative Study on the
      Genetics of Alcoholism data. Ethnic heterogeneity, highly skewed quantitative
      measures, and a high rate of missing values are all present in this dataset and
      well known to impact upon linkage analysis. This makes it a good candidate for
      investigation. RESULTS: As expected, we observed a number of changes in LOD
      scores, especially for chromosomes 1, 7, and 18, along with the three factors
      studied. A dramatic example of such changes can be found in chromosome 7. Highly
      significant linkage to one of the quantitative traits became insignificant when a
      proper normalizing transformation of the trait was used and when analysis was
      carried out on an ethnically homogeneous subset of the original pedigrees.
      CONCLUSION: In agreement with existing literature, transforming a trait to ensure
      normality using a Box-Cox transformation is highly recommended in order to avoid
      false-positive linkages. Furthermore, pedigrees should be sorted by ethnic groups
      and analyses should be carried out separately. Finally, one should be aware that
      the inclusion of covariates with a high rate of missing values reduces
      considerably the number of subjects included in the model. In such a case, the
      loss in power may be large. Imputation methods are then recommended.

PMID- 16451665
TI  - Application of a rank-based genetic association test to age-at-onset data from
      the Collaborative Study on the Genetics of Alcoholism study.
AB  - Association studies of quantitative traits have often relied on methods in which
      a normal distribution of the trait is assumed. However, quantitative phenotypes
      from complex human diseases are often censored, highly skewed, or contaminated
      with outlying values. We recently developed a rank-based association method that
      takes into account censoring and makes no distributional assumptions about the
      trait. In this study, we applied our new method to age-at-onset data on ALDX1 and
      ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We
      performed a whole genome association study of age at onset of the ALDX1 trait
      using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of
      markers were significant. However, we identified two regions on chromosomes 14
      and 15, which each have at least four significant markers clustering together.
      These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2.
      Future fine mapping of these two regions with densely spaced markers is
      warranted.

PMID- 16451666
TI  - Critical values and variation in type I error along chromosomes in the COGA
      dataset using the applied pseudo-trait method.
AB  - BACKGROUND: By analyzing a "pseudo-trait," a trait not linked or associated with
      any of the markers tested, the distribution of the test statistic under the null
      hypothesis can provide the critical value for the appropriate percentile of the
      distribution. In addition, the anecdotal observation that p-values tend to be
      more significant near the telomeres was investigated. RESULTS: The applied pseudo
      trait (APT) method was applied to the Affymetrix and Illumina SNPs in the
      Collaborative Study on the Genetics of Alcoholism dataset to determine
      appropriate critical values for regression of offspring on mid-parent (ROMP) and
      Haseman-Elston association and linkage analyses, investigating the occurrence of
      type I errors in different chromosomal locations, and the extent to which the
      critical values obtained depend on the type of pseudo-trait used. CONCLUSION: On
      average, the 5 percentile critical values obtained for this study were less than
      the expected 0.05. The distribution of p-values does not seem to depend on
      chromosomal position for ROMP association analysis methods, but does in some
      cases for Haseman-Elston linkage analysis. Results vary with different pseudo
      traits.

PMID- 16451667
TI  - Surrogate phenotype definition for alcohol use disorders: a genome-wide search
      for linkage and association.
AB  - For the identification of susceptibility loci in complex diseases the choice of
      the target phenotype is very important. We compared results of genome-wide
      searches for linkage or for association related to three phenotypes for alcohol
      use disorder. These are a behavioral score BQ, based on a 12-item questionnaire
      about drinking behavior and the subject's report of drinking-related health
      problems, and ERP pattern and ERP magnitude, both derived from the eyes closed
      resting ERP measures to quantify brain activity. Overall, we were able to
      identify 11 candidate regions for linkage. Only two regions were found to be
      related to both BQ and one of the ERP phenotypes. The genome-wide search for
      association using single-nucleotide polymorphisms did not yield interesting
      leads.

PMID- 16451668
TI  - Application of the regression of offspring on mid-parent method to detect
      associations between single-nucleotide polymorphisms and the beta 2
      electroencephalogram phenotype in the COGA data.
AB  - The beta 2 electroencephalogram (EEG) phenotype is used as a quantitative measure
      related to alcoholism, and evidence of linkage and association has previously
      been reported in the Collaborative Study on the Genetics of Alcoholism data. In
      this study, associations between the beta 2 EEG phenotype and single nucleotide
      polymorphisms from whole-genome Illumina and Affymetrix panels were investigated
      with the regression of offspring on mid-parent method to identify significant
      genetic effects and to estimate their heritability. Separate regressions on
      father and mother were performed to identify parent-specific effects. Estimates
      of the heritability of the beta 2 EEG phenotype were 0.68 +/- 0.12 and 0.52 +/-
      0.07 based on father-offspring and mother-offspring pairs, respectively.
      Significant associations at the 0.0005 level, some of which were parent-specific,
      were found on chromosomes 1, 2, 5, 6, 7, 8, 11, 12, 15, 16, 17, 18, and 19 with
      heritability attributable to each SNP ranging from 0.01 to 8%.

PMID- 16451669
TI  - A comparison of discrete versus continuous environment in a variance components
      based linkage analysis of the COGA data.
AB  - BACKGROUND: The information content of a continuous variable exceeds that of its
      categorical counterpart. The parameterization of a model may diminish the benefit
      of using a continuous variable. We explored the use of continuous versus discrete
      environment in variance components based analyses examining gene x environment
      interaction in the electrophysiological phenotypes from the Collaborative Study
      on the Genetics of Alcoholism. RESULTS: The parameterization using the continuous
      environment produced a greater number of significant gene x environment
      interactions and lower AICs (Akaike's information criterion). In these cases, the
      genetic variance increased with increasing cigarette pack-years, the continuous
      environment of interest. This did not, however, result in enhanced LOD scores
      when linkage analyses incorporated the gene x continuous environment interaction.
      CONCLUSION: Alternative parameterizations may better represent the functional
      relationship between the continuous environment and the genetic variance.

PMID- 16451670
TI  - A variance component analysis on recombination rate in the COGA pedigrees.
AB  - We estimated the crossover frequency in 1,232 gametes from 356 subjects in
      pedigrees from the Collaborative Study on the Genetics on Alcoholism. We examined
      the effect of covariates including age, ethnicity, and years with ALDX1 on
      recombination rate, and found a positive correlation between recombination rate
      and years with ALDX1. By variance-component analysis, we estimated the
      heritability of recombination rate to be around 0.5, and provided suggestive
      evidence for a locus linked to recombination rate.

PMID- 16451671
TI  - Linkage and association analysis in pedigrees from different populations.
AB  - Using the Genetic Analysis Workshop 14 simulated datasets we carried out
      nonparametric linkage analyses and applied a log-linear method for analysis of
      case-parent-triad data with stratification on parental mating type. We proposed
      and applied a random effect modelling approach to explore the impact of
      population heterogeneity on tests of association between genetic markers and
      disease status. The estimated genetic effect may appear to be strongly
      significant in one population but nonsignificant in another population, leading
      to confusion about interpretation. However, when results are interpreted in the
      light of a random effects model, both studies may be making similar statements
      about a genetic effect that varies depending on environment and background.

PMID- 16451672
TI  - The effect of linkage disequilibrium on linkage analysis of incomplete pedigrees.
AB  - Dense SNP maps can be highly informative for linkage studies. But when parental
      genotypes are missing, multipoint linkage scores can be inflated in regions with
      substantial marker-marker linkage disequilibrium (LD). Such regions were observed
      in the Affymetrix SNP genotypes for the Genetic Analysis Workshop 14 (GAW14)
      Collaborative Study on the Genetics of Alcoholism (COGA) dataset, providing an
      opportunity to test a novel simulation strategy for studying this problem. First,
      an inheritance vector (with or without linkage present) is simulated for each
      replicate, i.e., locations of recombinations and transmission of parental
      chromosomes are determined for each meiosis. Then, two sets of founder haplotypes
      are superimposed onto the inheritance vector: one set that is inferred from the
      actual data and which contains the pattern of LD; and one set created by randomly
      selecting parental alleles based on the known allele frequencies, with no
      correlation (LD) between markers. Applying this strategy to a map of 176 SNPs (66
      Mb of chromosome 7) for 100 replicates of 116 sibling pairs, significant
      inflation of multipoint linkage scores was observed in regions of high LD when
      parental genotypes were set to missing, with no linkage present. Similar
      inflation was observed in analyses of the COGA data for these affected sib pairs
      with parental genotypes set to missing, but not after reducing the marker map
      until r2 between any pair of markers was <or= 0.05. Additional simulation studies
      of affected sib pairs assuming uniform LD throughout a marker map demonstrated
      inflation of significance levels at r2 values greater than 0.05. When genotypes
      are available only from two affected siblings in many families in a sample,
      trimming SNP maps to limit r2 to 0-0.05 for all marker pairs will prevent
      inflation of linkage scores without sacrificing substantial linkage information.
      Simulation studies on the observed pedigree structures and map can also be used
      to determine the effect of LD on a particular study.

PMID- 16451673
TI  - Locally weighted transmission/disequilibrium test for genetic association
      analysis.
AB  - The transmission/disequilibrium test statistic has been used for assessing
      genetic association in affected-parent trios. In the presence of multiple tightly
      linked marker loci where local dependency may exist, haplotypes are reconstructed
      statistically to estimate the joint effects of these markers. In this manuscript,
      we propose an alternative to the haplotype approach by taking a weighted average
      of multiple loci, where the weight is proportional to the product of (1-2X
      recombination fraction) and the linkage disequilibrium between markers. As an
      illustration, we applied the method to the simulated Aipotu data.

PMID- 16451674
TI  - Optimizing the evidence for linkage by permuting marker order.
AB  - We developed a new marker-reordering algorithm to find the best order of fine
      mapping markers for multipoint linkage analysis. The algorithm searches for the
      best order of fine-mapping markers such that the sum of the squared differences
      in identity-by-descent distribution between neighboring markers is minimized. To
      test this algorithm, we examined its effect on the evidence for linkage in the
      simulated and the Collaborative Studies on Genetics of Alcoholism (COGA) data. We
      found enhanced evidence for linkage with the reordered map at the true location
      in the simulated data (p-value decreased from 1.16 x 10(-9) to 9.70 x 10(-10)).
      Analysis of the White population from the COGA data with the reordered map for
      alcohol dependence led to a significant change of the linkage signal (p = 0.0365
      decreased to p = 0.0039) on chromosome 1 between marker D1S1592 and D1S1598. Our
      results suggest that reordering fine-mapping markers in candidate regions when
      the genetic map is uncertain can be a critical step when considering a dense map.

PMID- 16451675
TI  - Comparison of family-based association tests in chromosome regions selected by
      linkage-based confidence intervals.
AB  - We use the Genetic Analysis Workshop 14 simulated data to explore the
      effectiveness of a two-stage strategy for mapping complex disease loci consisting
      of an initial genome scan with confidence interval construction for gene
      location, followed by fine mapping with family-based tests of association on a
      dense set of single-nucleotide polymorphisms. We considered four types of
      intervals: the 1-LOD interval, a basic percentile bootstrap confidence interval
      based on the position of the maximum Zlr score, and asymptotic and bootstrap
      confidence intervals based on a generalized estimating equations method. For fine
      mapping we considered two family-based tests of association: a test based on a
      likelihood ratio statistic and a transmission-disequilibrium-type test
      implemented in the software FBAT. In two of the simulation replicates, we found
      that the bootstrap confidence intervals based on the peak Zlr and the 1-LOD
      support interval always contained the true disease loci and that the likelihood
      ratio test provided further strong confirmatory evidence of the presence of
      disease loci in these regions.

PMID- 16451677
TI  - Potts model for haplotype associations.
AB  - Bayesian spatial modeling has become important in disease mapping and has also
      been suggested as a useful tool in genetic fine mapping. We have implemented the
      Potts model and applied it to the Genetic Analysis Workshop 14 (GAW14) simulated
      data. Because the "answers" were known we have analyzed latent phenotype P1
      related observed phenotypes affection status (genetically determined) and i
      (random) in the Danacaa population replicate 2. Analysis of the
      microsatellite/single-nucleotide polymorphism-based haplotypes at chromosomes 1
      and 3 failed to identify multiple clusters of haplotype effects. However, the
      analysis of separately simulated data with postulated differences in the effects
      of the two clusters has yielded clear estimated division into the two clusters,
      demonstrating the correctness of the algorithm. Although we could not clearly
      identify the disease-related and the non-associated groups of haplotypes, results
      of both GAW14 and our own simulation encourage us to improve the efficiency and
      sensitivity of the estimation algorithm and to further compare the proposed
      method with more traditional methods.

PMID- 16451676
TI  - Fine mapping--19th century style.
AB  - BACKGROUND: There is great interest in the use of computationally intensive
      methods for fine mapping of marker data. In this paper we develop methods based
      upon ideas originally proposed 100 years ago in the context of spatial
      clustering. METHODS: We use spatial clustering of haplotypes as a low-dimensional
      surrogate for the unobserved genealogy underlying a set of genotype data. In
      doing so we hope to avoid the computational complexity inherent in explicitly
      modelling details of the ancestry of the sample, while at the same time capturing
      the key correlations induced by that ancestry at a much lower computational cost.
      RESULTS: We benchmark our methods using the simulated Genetic Analysis Workshop
      14 data, using 100 replicates of 4 phenotypes to indicate the power of our
      method. When a functional mutation relating to a trait is actually present, we
      find evidence for that mutation in 97 out of 100 replicates, on average.
      CONCLUSION: Our results show that our method has the ability to accurately infer
      the location of functional mutations from unphased genotype data.

PMID- 16451678
TI  - Comparison of genotype- and haplotype-based approaches for fine-mapping of
      alcohol dependence using COGA data.
AB  - It is generally assumed that the detection of disease susceptibility genes via
      fine-mapping association study is facilitated by consideration of marker
      haplotypes. In this study, we compared the performance of genotype-based and
      haplotype-based association studies using the Collaborative Study of Genetics of
      Alcoholism dataset, on several chromosomal regions showing evidence for linkage
      with ALDX1. After correction for multiple testing, the most significant results
      were observed with the genotype-based analyses on two regions of chromosomes 2
      and 7. Interestingly, the analyses results from this dataset showed that there
      was no advantage of the haplotype-based analyses over genotype-based (single
      locus) analyses. However, caution should be taken when generalizing these results
      to other chromosomal regions or to other populations.

PMID- 16451679
TI  - Will the real disease gene please stand up?
AB  - A common dilemma arising in linkage studies of complex genetic diseases is the
      selection of positive signals, their follow-up with association studies and
      discrimination between true and false positive results. Several strategies for
      overcoming these issues have been devised. Using the Genetic Analysis Workshop 14
      simulated dataset, we aimed to apply different analytical approaches and evaluate
      their performance in discerning real associations. We considered a) haplotype
      analyses, b) different methods adjusting for multiple testing, c) replication in
      a second dataset, and d) exhaustive genotyping of all markers in a sufficiently
      powered, large sample group. We found that haplotype-based analyses did not
      substantially improve over single-point analysis, although this may reflect the
      low levels of linkage disequilibrium simulated in the datasets provided. Multiple
      testing correction methods were in general found to be over-conservative.
      Replication of nominally positive results in a second dataset appears to be less
      stringent, resulting in the follow-up of false positives. Performing a
      comprehensive assay of all markers in a large, well-powered dataset appears to be
      the most effective strategy for complex disease gene identification.

PMID- 16451680
TI  - Fine-mapping using the weighted average method for a case-control study.
AB  - We present a new method for fine-mapping a disease susceptibility locus using a
      case-control design. The new method, termed the weighted average (WA) statistic,
      averages the Cochran-Armitage (CA) trend test statistic and the difference
      between the Hardy-Weinberg disequilibrium test statistic for cases and controls
      (the HWD trend). The main characteristics of the WA statistic are that it
      improves on the weaknesses, and maintains the strengths, of both the CA trend
      test and the HWD trend test. Data from three different populations in the Genetic
      Analysis Workshop 14 (GAW14) simulated dataset (Aipotu, Karangar, and Danacaa)
      were first subjected to model-free linkage analysis to find regions exhibiting
      linkage. Then, for fine-scale mapping, 140 SNPs within the significant linkage
      regions were analyzed with the WA test statistic on replicates of the three
      populations, both separately and combined. The regions that were significant in
      the multipoint linkage analysis were also significant in this fine-scale mapping.
      The most significant regions that were obtained using the WA statistic were
      regions in chromosome 3 (B03T3056-B03T3058, p-value < 1 x 10(-10)) and chromosome
      9 (B09T8332-B09T8334, p-value 1 x 10(-6)). Based on the results of the simulated
      GAW14 data, the WA test statistic showed good performance and could narrow down
      the region containing the susceptibility locus. However, the strength of the
      signal depends on both the strength of the linkage disequilibrium and the
      heterozygosity of the linked marker.

PMID- 16451681
TI  - Application of family-based association testing to assess the genotype-phenotype
      association involved in complex traits using single-nucleotide polymorphisms.
AB  - BACKGROUND: We used the FBAT (family-based association test) software to test for
      association between 300 individual single-nucleotide polymorphisms and P1 (a
      latent trait of Kofendred Personality Disorder) in 100 simulated replicates of
      the Aipotu population. Using the Genetic Analysis Workshop 14 dataset, we
      calculated the power of FBAT to detect linkage disequilibrium on chromosome 3
      (D2). Also, we calculated the false-positive rate on chromosome 1, which contains
      a true locus (D1) but no linkage disequilibrium was simulated between the trait
      and all the surrounding single-nucleotide polymorphisms. RESULTS: We were able to
      detect the associations between phenotype P1 and three adjacent markers B03T3056
      (average p-value = 0.0002), B03T3057 (average p-value = 0.00072), and B03T3058
      (average p-value = 0.0038) with power of 98%, 87%, 71% on chromosome 3,
      respectively. The overall false positive rate to detect association was 0.06 on
      chromosome 1. CONCLUSION: The power to detect a significant association in 100
      nuclear families affected with the latent trait of Kofendred Personality Disorder
      by using FBAT was reasonable (based on 100 replicates). In the future, we will
      compare the performance of FBAT with alternative approaches, such as using FBAT
      generalized estimating equations methods to test for association in families
      affected with complex traits.

PMID- 16451682
TI  - Robust testing of haplotype/disease association.
AB  - Haplotypes, the combination of closely linked alleles that fall on the same
      chromosome, show great promise for studying the genetic components of complex
      diseases. However, when only multilocus genotype data are available, statistical
      approaches need to be employed to resolve haplotype phase ambiguity. Recently, we
      have proposed an approach to testing and estimating haplotype/disease association
      that is invariant to any existing genetic structure in the population. Here we
      evaluate this approach by applying it to the Genetic Analysis Workshop 14
      simulated data.

PMID- 16451684
TI  - Haplotype-sharing analysis using Mantel statistics for combined genetic effects.
AB  - We applied a new approach based on Mantel statistics to analyze the Genetic
      Analysis Workshop 14 simulated data with prior knowledge of the answers. The
      method was developed in order to improve the power of a haplotype sharing
      analysis for gene mapping in complex disease. The new statistic correlates
      genetic similarity and phenotypic similarity across pairs of haplotypes from case
      control studies. The genetic similarity is measured as the shared length between
      haplotype pairs around a genetic marker. The phenotypic similarity is measured as
      the mean corrected cross-product based on the respective phenotypes. Cases with
      phenotype P1 and unrelated controls were drawn from the population of Danacaa.
      Power to detect main effects was compared to the X2-test for association based on
      3-marker haplotypes and a global permutation test for haplotype association to
      test for main effects. Power to detect gene x gene interaction was compared to
      unconditional logistic regression. The results suggest that the Mantel statistics
      might be more powerful than alternative tests.

PMID- 16451683
TI  - Comparison of the power between microsatellite and single-nucleotide polymorphism
      markers for linkage and linkage disequilibrium mapping of an electrophysiological
      phenotype.
AB  - We performed linkage and linkage disequilibrium (LD) mapping analyses to compare
      the power between microsatellite and single nucleotide polymorphism (SNP)
      markers. Chromosome-wide analyses were performed for a quantitative
      electrophysiological phenotype, ttth1, on chromosome 7. Multipoint analysis of
      microsatellite markers using the variance component (VC) method showed the
      highest LOD score of 4.20 at 162 cM, near D7S509 (163.7 cM). Two-point analysis
      of SNPs using the VC method yielded the highest LOD score of 3.98 in the Illumina
      SNP data and 3.45 in the Affymetrix SNP data around 152-153 cM. In family-based
      single SNP and SNP haplotype LD analysis, we identified seven SNPs associated
      with ttth1. We searched for any potential candidate genes in the location of the
      seven SNPs. The SNPs rs1476640 and rs768055 are located in the FLJ40852 gene (a
      hypothetical protein), and SNP rs1859646 is located in the TAS2R5 gene (a taste
      receptor). The other four SNPs are not located in any known or annotated genes.
      We found the high density SNP scan to be superior to microsatellites because it
      is effective in downstream fine mapping due to a better defined linkage region.
      Our study proves the utility of high density SNP in genome-wide mapping studies.

PMID- 16451685
TI  - A comparison of five methods for selecting tagging single-nucleotide
      polymorphisms.
AB  - Our goal was to compare methods for tagging single-nucleotide polymorphisms
      (tagSNPs) with respect to the power to detect disease association under differing
      haplotype-disease association models. We were also interested in the effect that
      SNP selection samples, consisting of either cases, controls, or a mixture, would
      have on power. We investigated five previously described algorithms for choosing
      tagSNPS: two that picked SNPs based on haplotype structure (Chapman-haplotypic
      and Stram), two that picked SNPs based on pair-wise allelic association (Chapman
      allelic and Cousin), and one control method that chose equally spaced SNPs
      (Zhai). In two disease-associated regions from the Genetic Analysis Workshop 14
      simulated data, we tested the association between tagSNP genotype and disease
      over the tagSNP sets chosen by each method for each sampling scheme. This was
      repeated for 100 replicates to estimate power. The two allelic methods chose
      essentially all SNPs in the region and had nearly optimal power. The two
      haplotypic methods chose about half as many SNPs. The haplotypic methods had poor
      performance compared to the allelic methods in both regions. We expected an
      improvement in power when the selection sample contained cases; however, there
      was only moderate variation in power between the sampling approaches for each
      method. Finally, when compared to the haplotypic methods, the reference method
      performed as well or worse in the region with ancestral disease haplotype
      structure.

PMID- 16451686
TI  - Strategies for selecting subsets of single-nucleotide polymorphisms to genotype
      in association studies.
AB  - In genetic association studies, linkage disequilibrium (LD) within a region can
      be exploited to select a subset of single-nucleotide polymorphisms (SNPs) to
      genotype with minimal loss of information. A novel entropy-based method for
      selecting SNPs is proposed and compared to an existing method based on the
      coefficient of determination (R2) using simulated data from Genetic Analysis
      Workshop 14. The effect of the size of the sample used to investigate LD (by
      estimating haplotype frequencies) and hence select the SNPs is also investigated
      for both measures. It is found that the novel method and the established method
      select SNP subsets that do not differ greatly. The entropy-based measure may thus
      have value because it is easier to compute than R2. Increasing the sample size
      used to estimate haplotype frequencies improves the predictive power of the
      subset of SNPs selected. A smaller subset of SNPs chosen using a large initial
      sample to estimate LD can in some instances be more informative than a larger
      subset chosen based on poor estimates of LD (using a small initial sample). An
      initial sample size of 50 individuals is sufficient in most situations
      investigated, which involved selection from a set of 7 SNPs, although to select a
      larger number of SNPs, a larger initial sample size may be required.

PMID- 16451688
TI  - Fine-scale mapping in case-control samples using locus scoring and haplotype
      sharing methods.
AB  - Both haplotype-based and locus-based methods have been proposed as the most
      powerful methods to employ when fine mapping by association. Although haplotype
      based methods utilize more information, they may lose power as a result of
      overparameterization, given the large number of haplotypes possible over even a
      few loci. Recently methods have been developed that cluster haplotypes with
      similar structure in the hope that this reflects shared genealogical ancestry.
      The aim is to reduce the number of parameters while retaining the genotype
      information relating to disease susceptibility. We have compared several
      haplotype-based methods with locus-based methods. We utilized 2 regions (D2 and
      D4) simulated to be in linkage disequilibrium and to be associated with disease
      susceptibility, combining 5 replicates at a time to produce 4 datasets that were
      analyzed. We found little difference in the performance of the haplotype-based
      methods and the locus-based methods in this dataset.

PMID- 16451687
TI  - Identification of tag single-nucleotide polymorphisms in regions with varying
      linkage disequilibrium.
AB  - We compared seven different tagging single-nucleotide polymorphism (SNP) programs
      in 10 regions with varied amounts of linkage disequilibrium (LD) and physical
      distance. We used the Collaborative Studies on the Genetics of Alcoholism
      dataset, part of the Genetic Analysis Workshop 14. We show that in regions with
      moderate to strong LD these programs are relatively consistent, despite different
      parameters and methods. In addition, we compared the selected SNPs in a
      multipoint linkage analysis for one region with strong LD. As the number of
      selected SNPs increased, the LOD score, mean information content, and type I
      error also increased.

PMID- 16451689
TI  - Haplotype-sharing analysis for alcohol dependence based on quantitative traits
      and the Mantel statistic.
AB  - Haplotype-based methods have become increasingly popular in the last decade
      because shared lengths in haplotypes can be used for disease localization. In
      this contribution, we propose a novel linkage-based haplotype-sharing approach
      for quantitative traits based on the class of Mantel statistics which is closely
      related to the weighted pair-wise correlation statistic. Because these statistics
      are known to be liberal, we propose a permutation test to evaluate significance.
      We applied the Mantel statistic to the autosomal data from the genome-wide scan
      of the Collaborative Study on the Genetics of Alcoholism with the Affymetrix
      Genotype 10 K array that was provided for the Genetic Analysis Workshop 14. Four
      regions on chromosome 4, 8, 16, and 20 showed p-values less than 0.005 with a
      minimum p-value of < 0.0001 on chromosome 16 (tsc0520638 at 72.8 cM). Three of
      these four regions located on chromosome 4, 16, and 20 have been reported
      previously in the Genetic Analysis Workshop 11.

PMID- 16451690
TI  - Comparisons of methods for linkage analysis and haplotype reconstruction using
      extended pedigree data.
AB  - We compare and contrast the performance of SIMPLE, a Monte Carlo based software,
      with that of several other methods for linkage and haplotype analyses, focusing
      on the simulated data from the New York City population. First, a whole-genome
      scan study based on the microsatellite markers was performed using GENEHUNTER.
      Because GENEHUNTER had to drop individuals for many of the pedigrees, we
      performed a follow-up study focusing on several regions of interest using SIMPLE,
      which can handle all pedigrees in their entirety. Second, 3 haplotyping programs,
      including that in SIMPLE, were used to reconstruct haplotypic configurations in
      pedigrees. SIMPLE emerges clearly as a preferred tool, as it can handle large
      pedigrees and produces haplotypic configurations without double recombinant
      haplotypes. For this study, we had knowledge of the simulating models at the time
      we performed the analysis.

PMID- 16451691
TI  - Haplotypic structure of the X chromosome in the COGA population sample and the
      quality of its reconstruction by extant software packages.
AB  - BACKGROUND: The haplotypes of the X chromosome are accessible to direct count in
      males, whereas the diplotypes of the females may be inferred knowing the
      haplotype of their sons or fathers. Here, we investigated: 1) the possible large
      scale haplotypic structure of the X chromosome in a Caucasian population sample,
      given the single-nucleotide polymorphism (SNP) maps and genotypes provided by
      Illumina and Affimetrix for Genetic Analysis Workshop 14, and, 2) the
      performances of widely used programs in reconstructing haplotypes from population
      genotypic data, given their known distribution in a sample of unrelated
      individuals. RESULTS: All possible unrelated mother-son pairs of Caucasian
      ancestry (N = 104) were selected from the 143 families of the Collaborative Study
      on the Genetics of Alcoholism pedigree files, and the diplotypes of the mothers
      were inferred from the X chromosomes of their sons. The marker set included 313
      SNPs at an average density of 0.47 Mb. Linkage disequilibrium between pairs of
      markers was computed by the parameter D', whereas for measuring multilocus
      disequilibrium, we developed here an index called D*, and applied it to all
      possible sliding windows of 5 markers each. Results showed a complex pattern of
      haplotypic structure, with regions of low linkage disequilibrium separated by
      regions of high values of D*. The following programs were evaluated for their
      accuracy in inferring population haplotype frequencies: 1) ARLEQUIN 2.001; 2)
      PHASE 2.1.1; 3) SNPHAP 1.1; 4) HAPLOBLOCK 1.2; 5) HAPLOTYPER 1.0. Performances
      were evaluated by Pearson correlation (r) coefficient between the true and the
      inferred distribution of haplotype frequencies. CONCLUSION: The SNP haplotypic
      structure of the X chromosome is complex, with regions of high haplotype
      conservation interspersed among regions of higher haplotype diversity. All the
      tested programs were accurate (r = 1) in reconstructing the distribution of
      haplotype frequencies in case of high D* values. However, only the program PHASE
      realized a high correlation coefficient (r > 0.7) in conditions of low linkage
      disequilibrium.

PMID- 16451692
TI  - Comparison of type I error for multiple test corrections in large single
      nucleotide polymorphism studies using principal components versus haplotype
      blocking algorithms.
AB  - Although permutation testing has been the gold standard for assessing
      significance levels in studies using multiple markers, it is time-consuming. A
      Bonferroni correction to the nominal p-value that uses the underlying pair-wise
      linkage disequilibrium (LD) structure among the markers to determine the number
      of effectively independent tests has recently been proposed. We propose using the
      number of independent LD blocks plus the number of independent single-nucleotide
      polymorphisms for correction. Using the Collaborative Study on the Genetics of
      Alcoholism LD data for chromosome 21, we simulated 1,000 replicates of parent
      child trio data under the null hypothesis with two levels of LD: moderate and
      high. Assuming haplotype blocks were independent, we calculated the number of
      independent statistical tests using 3 haplotype blocking algorithms. We then
      compared the type I error rates using a principal components-based method, the
      three blocking methods, a traditional Bonferroni correction, and the unadjusted p
      values obtained from FBAT. Under high LD conditions, the PC method and one of the
      blocking methods were slightly conservative, whereas the 2 other blocking methods
      exceeded the target type I error rate. Under conditions of moderate LD, we show
      that the blocking algorithm corrections are closest to the desired type I error,
      although still slightly conservative, with the principal components-based method
      being almost as conservative as the traditional Bonferroni correction.

PMID- 16451693
TI  - Haplotype sharing correlation of alcohol dependence on chromosomes 1-6 in 93
      nuclear families.
AB  - Haplotype data contain signatures of ancestral alleles and increased information
      for mapping genes associated with complex traits. The motivation of this paper is
      to test the feasibility of a recently developed haplotype reconstruction
      algorithm and to perform haplotype-sharing correlation (HSC) analysis in nuclear
      families using data provided by the Genetic Analysis Workshop 14 and the
      Collaborative Study of the Genetics of Alcoholism. As an exemplary analysis,
      haplotype data on chromosomes 1-6 were reconstructed from genotype data in 93
      nuclear families by minimizing both the recombinants in within-family haplotypes
      and the tree distance in between-family haplotypes. HSC analysis was performed
      using the best set of reconstructed haplotypes, and chromosome-wide significance
      was evaluated using a permutation procedure. Three markers were found to have
      significant haplotype associations with DSM-IV alcohol dependence that exceeded
      the 0.05 level of chromosome-wide significance: marker rs895941 at 36.7 cM on
      chromosome 3 (p = 0.03), marker rs1631833 at 109.1 cM on chromosome 4 (p =
      0.008), and marker rs953887 at 74.2 cM on chromosome 6 (p = 0.02). These results
      indicated the usefulness of HSC analysis and provided further evidence on
      chromosome regions associated with alcohol dependence.

PMID- 16451694
TI  - Genome-wide linkage analysis for alcohol dependence: a comparison between single
      nucleotide polymorphism and microsatellite marker assays.
AB  - Both theoretical and applied studies have proven that the utility of single
      nucleotide polymorphism (SNP) markers in linkage analysis is more powerful and
      cost-effective than current microsatellite marker assays. Here we performed a
      whole-genome scan on 115 White, non-Hispanic families segregating for alcohol
      dependence, using one 10.3-cM microsatellite marker set and two SNP data sets
      (0.33-cM, 0.78-cM spacing). Two definitions of alcohol dependence (ALDX1 and
      ALDX2) were used. Our multipoint nonparametric linkage analysis found alcoholism
      was nominal linked to 12 genomic regions. The linkage peaks obtained by using the
      microsatellite marker set and the two SNP sets had a high degree of
      correspondence in general, but the microsatellite marker set was insufficient to
      detect some nominal linkage peaks. The presence of linkage disequilibrium between
      markers did not significantly affect the results. Across the entire genome, SNP
      datasets had a much higher average linkage information content (0.33 cM: 0.93,
      0.78 cM: 0.91) than did microsatellite marker set (0.57). The linkage peaks
      obtained through two SNP datasets were very similar with some minor differences.
      We conclude that genome-wide linkage analysis by using approximately 5,000 SNP
      markers evenly distributed across the human genome is sufficient and might be
      more powerful than current 10-cM microsatellite marker assays.

PMID- 16451695
TI  - Accuracy of haplotype estimation in a region of low linkage disequilibrium.
AB  - We compared the accuracy of haplotype inferences at a 6 Mb region on chromosome 7
      where significant linkage between a brain oscillation phenotype and a cholinergic
      muscarinic receptor gene was previously reported. Individual haplotype
      assignments and haplotype frequencies were estimated using 5, 10, and 14
      consecutive Illumina single-nucleotide polymorphisms (SNPs) within the 1-LOD unit
      support interval of the chromosome 7 linkage peak. Initially, haplotypes were
      constructed incorporating phase information provided by relatives using the
      pedigree analysis package MERLIN. Population-based haplotypes were inferred using
      the haplotype estimation software HAPLO.STATS and PHASE, using unrelated
      individuals. The 14 SNPs within this region exhibited markedly low linkage
      disequilibrium, and the average D' estimate between SNPs was 0.18 (range: 0.01
      0.97). In comparison to the family-based haplotypes calculated in MERLIN, the
      computational inferences of individual haplotype assignments were most accurate
      when considering 5 consecutive SNPs, but decayed dramatically when considering 10
      or 14 SNPs in both PHASE and HAPLO.STATS. When comparing the two haplotype
      inference methods, both PHASE and HAPLO.STATS performed poorly. These analyses
      underscore the difficulties of haplotype estimation in the presence of low
      linkage disequilibrium and stress the importance of careful consideration of
      confidence measures when using estimated haplotype frequencies and individual
      assignments in biomedical research.

PMID- 16451696
TI  - An exploration of sex-specific linkage disequilibrium on chromosome X in
      Caucasians from the COGA study.
AB  - This paper explores the decay of linkage disequilibrium (LD) on the autosomes and
      chromosome X. The extent of marker-marker LD is important for both linkage and
      association studies. The analysis of the Caucasian sample from the Collaborative
      Study on the Genetics of Alcoholism study revealed the expected negative
      relationship between the magnitude of the marker-marker LD and distance (cM),
      with the male and female subgroups exhibiting similar patterns of LD. The
      observed extent of LD in females was less across the pseudoautosomal markers
      relative to the heterosomal region of chromosome X. Marked differences in LD
      patterns were also observed between chromosomes X and the 22 autosomes in both
      males and females.

PMID- 16451697
TI  - Bias of allele-sharing linkage statistics in the presence of intermarker linkage
      disequilibrium.
AB  - Current genome-wide linkage-mapping single-nucleotide polymorphism (SNP) panels
      with densities of 0.3 cM are likely to have increased intermarker linkage
      disequilibrium (LD) compared to 5-cM microsatellite panels. The resulting
      difference in haplotype frequencies versus that predicted may affect multipoint
      linkage analysis with ungenotyped founders; a common haplotype may be assumed to
      be rare, leading to inflation of identical-by-descent (IBD) allele-sharing
      estimates and evidence for linkage. Using data simulated for the Genetic Analysis
      Workshop 14, we assessed bias in allele-sharing measures and nonparametric
      linkage (NPL all) and Kong and Cox LOD (KC-LOD) scores in a targeted analysis of
      regions with and without LD and with and without genes. Using over 100
      replicates, we found that if founders were not genotyped, multipoint IBD
      estimates and delta parameters were modestly inflated and NPL all and KC-LOD
      scores were biased upwards in the region with LD and no gene; rather than
      centering on the null, the mean NPL all and KC-LOD scores were 0.51 +/- 0.91 and
      0.19 +/- 0.38, respectively. Reduction of LD by dropping markers reduced this
      upward bias. These trends were not seen in the non-LD region with no gene. In
      regions with genes (with and without LD), a slight loss in power with dropping
      markers was suggested. These results indicate that LD should be considered in
      dense scans; removal of markers in LD may reduce false-positive results although
      information may also be lost. Methods to address LD in a high-throughput manner
      are needed for efficient, robust genomic scans with dense SNPs.

PMID- 16451698
TI  - Examining the effect of linkage disequilibrium on multipoint linkage analysis.
AB  - Most linkage programs assume linkage equilibrium among multiple linked markers.
      This assumption may lead to bias for tightly linked markers where strong linkage
      disequilibrium (LD) exists. We used simulated data from Genetic Analysis Workshop
      14 to examine the possible effect of LD on multipoint linkage analysis. Single
      nucleotide polymorphism packets from a non-disease-related region that was
      generated with LD were used for both model-free and parametric linkage analyses.
      Results showed that high LD among markers can induce false-positive evidence of
      linkage for affected sib-pair analysis when parental data are missing. Bias can
      be eliminated with parental data and can be reduced when additional markers not
      in LD are included in the analyses.

PMID- 16451699
TI  - The efficacy of short tandem repeat polymorphisms versus single-nucleotide
      polymorphisms for resolving population structure.
AB  - Accurately resolving population structure in a sample is important for both
      linkage and association studies. In this study we investigated the power of
      single-nucleotide polymorphisms (SNPs) in detecting population structure in a
      sample of 286 unrelated individuals. We varied the number of SNPs to determine
      how many are required to approach the degree of resolution obtained with the
      Collaborative Study on the Genetics of Alcoholism (COGA) short tandem repeat
      polymorphisms (STRPs). In addition, we selected SNPs with varying minor allele
      frequencies (MAFs) to determine whether low or high frequency SNPs are more
      efficient in resolving population structure. We conclude that a set of at least
      100 evenly spaced SNPs with MAFs of 40-50% is required to resolve population
      structure in this dataset. If SNPs with lower MAFs are used, then more than 250
      SNPs may be required to obtain reliable results.

PMID- 16451700
TI  - Evaluation of linkage disequilibrium and its effect on non-parametric multipoint
      linkage analysis using two high density single-nucleotide polymorphism mapping
      panels.
AB  - Genotype data from the Illumina Linkage III SNP panel (n = 4,720 SNPs) and the
      Affymetrix 10 k mapping array (n = 11,120 SNPs) were used to test the effects of
      linkage disequilibrium (LD) between SNPs in a linkage analysis in the
      Collaborative Study on the Genetics of Alcoholism pedigree collection (143
      pedigrees; 1,614 individuals). The average r2 between adjacent markers across the
      genetic map was 0.099 +/- 0.003 in the Illumina III panel and 0.17 +/- 0.003 in
      the Affymetrix 10 k array. In order to determine the effect of LD between marker
      loci in a nonparametric multipoint linkage analysis, markers in strong LD with
      another marker (r2 > 0.40) were removed (n = 471 loci in the Illumina panel; n =
      1,804 loci in the Affymetrix panel) and the linkage analysis results were
      compared to the results using the entire marker sets. In all analyses using the
      ALDX1 phenotype, 8 linkage regions on 5 chromosomes (2, 7, 10, 11, X) were
      detected (peak markers p < 0.01), and the Illumina panel detected an additional
      region on chromosome 6. Analysis of the same pedigree set and ALDX1 phenotype
      using short tandem repeat markers (STRs) resulted in 3 linkage regions on 3
      chromosomes (peak markers p < 0.01). These results suggest that in this pedigree
      set, LD between loci with spacing similar to the SNP panels tested may not
      significantly affect the overall detection of linkage regions in a genome scan.
      Moreover, since the data quality and information content are greatly improved in
      the SNP panels over STR genotyping methods, new linkage regions may be identified
      due to higher information content and data quality in a dense SNP linkage panel.

PMID- 16451701
TI  - Linkage disequilibrium across two different single-nucleotide polymorphism genome
      scans.
AB  - Linkage disequilibrium (LD) content was calculated for the Genetic Analysis
      Workshop 14 Affymetrix and Illumina single-nucleotide polymorphism (SNP) genome
      scans of the Collaborative Study on the Genetics of Alcoholism samples. Pair-wise
      LD was measured as both D' and r2 on 505 pedigree founder individuals. The r2
      estimates were then used to correct the multipoint identity by descent matrix
      (MIBD) calculation to account for LD and LOD scores on chromosomes 3 and 18 were
      calculated for COGA's ttdt3 electrophysiological trait using those MIBDs.
      Extensive LD was observed throughout both marker sets, and it was higher in
      Affymetrix's more dense SNP map. However, SNP density did not solely account for
      Affymetrix's higher LD. MIBD estimation procedures assume linkage equilibrium to
      construct genotypes of non-genotyped pedigree founder individuals, and dense SNP
      genotyping maps are likely to contain moderate to high LD between markers. LOD
      score plots calculated after correction for LD followed the same general pattern
      as uncorrected ones. Since in our study almost half of the pedigree founders were
      genotyped, it is possible that LD had a minor impact on the LOD scores. Caution
      should probably be taken when using high density SNP maps when many non-genotyped
      founders are present in the study pedigrees.

PMID- 16451702
TI  - Modeling the effect of a genetic factor for a complex trait in a simulated
      population.
AB  - Genetic Analysis Workshop 14 simulated data have been analyzed with MASC(marker
      association segregation chi-squares) in which we implemented a bootstrap
      procedure to provide the variation intervals of parameter estimates. We model
      here the effect of a genetic factor, S, for Kofendrerd Personality Disorder in
      the region of the marker C03R0281 for the Aipotu population. The goodness of fit
      of several genetic models with two alleles for one locus has been tested. The
      data are not compatible with a direct effect of a single-nucleotide polymorphism
      (SNP) (SNP 16, 17, 18, 19 of pack 153) in the region. Therefore, we can conclude
      that the functional polymorphism has not been typed and is in linkage
      disequilibrium with the four studied SNPs. We obtained very large variation
      intervals both of the disease allele frequency and the degree of dominance. The
      uncertainty of the model parameters can be explained first, by the method used,
      which models marginal effects when the disease is due to complex interactions,
      second, by the presence of different sub-criteria used for the diagnosis that are
      not determined by S in the same way, and third, by the fact that the segregation
      of the disease in the families was not taken into account. However, we could not
      find any model that could explain the familial segregation of the trait, namely
      the higher proportion of affected parents than affected sibs.

PMID- 16451703
TI  - Identification of polymorphisms explaining a linkage signal: application to the
      GAW14 simulated data.
AB  - We applied three approaches for the identification of polymorphisms explaining
      the linkage evidence to the Genetic Analysis Workshop 14 simulated data: 1) the
      genotype-IBD sharing test (GIST); 2) an approach suggested by Horikawa and
      colleagues; and 3) the homozygote sharing test (HST). These tests were compared
      with a family-based association test. Two linked regions with highest
      nonparametric linkage scores were selected to apply these methods. In the first
      region, Horikawa's method identified the most SNPs within the region containing
      the disease susceptibility locus, while HST performed best in the second region.
      However, Horikawa's method also had the most type I errors. These methods show
      potential as additional tools to complement family-based association tests for
      the identification of disease susceptibility variants.

PMID- 16451704
TI  - A comparison in association and linkage genome-wide scans for alcoholism
      susceptibility genes using single-nucleotide polymorphisms.
AB  - We conducted genome-wide linkage scans using both microsatellite and single
      nucleotide polymorphism (SNP) markers. Regions showing the strongest evidence of
      linkage to alcoholism susceptibility genes were identified. Haplotype analyses
      using a sliding-window approach for SNPs in these regions were performed. In
      addition, we performed a genome-wide association scan using SNP data. SNPs in
      these regions with evidence of association (P <or= 0.0001) were identified. We
      found that the general patterns for nonparametric linkage (NPL) scores from SNP
      and microsatellite genome scans are fairly consistent; however, the peaks of the
      NPL scores are mostly higher in the SNP-based scan than those using
      microsatellite markers, which might be located at different regions. Furthermore,
      SNPs identified from linkage screens were not so strongly associated with
      alcoholism (the most significant SNP had a p-value of 0.030) as those identified
      from association genomic screening (the most significant SNP had a p-value of 2.0
      x 10(-8)).

PMID- 16451705
TI  - Whole-genome association studies of alcoholism with loci linked to schizophrenia
      susceptibility.
AB  - BACKGROUND: Alcoholism is a complex disease. There have been many reports on
      significant comorbidity between alcoholism and schizophrenia. For the genetic
      study of complex diseases, association analysis has been recommended because of
      its higher power than that of the linkage analysis for detecting genes with
      modest effects on disease. RESULTS: To identify alcoholism susceptibility loci,
      we performed genome-wide single-nucleotide polymorphisms (SNP) association tests,
      which yielded 489 significant SNPs at the 1% significance level. The association
      tests showed that tsc0593964 (P-value 0.000013) on chromosome 7 was most
      significantly associated with alcoholism. From 489 SNPs, 74 genes were
      identified. Among these genes, GABRA1 is a member of the same gene family with
      GABRA2 that was recently reported as alcoholism susceptibility gene. CONCLUSION:
      By comparing 74 genes to the published results of various linkage studies of
      schizophrenia, we identified 13 alcoholism associated genes that were located in
      the regions reported to be linked to schizophrenia. These 13 identified genes can
      be important candidate genes to study the genetic mechanism of co-occurrence of
      both diseases.

PMID- 16451706
TI  - Impact of non-ignorable missingness on genetic tests of linkage and/or
      association using case-parent trios.
AB  - The transmission/disequilibrium test was introduced to test for linkage
      disequilibrium between a marker and a putative disease locus using case-parent
      trios. However, parental genotypes may be incomplete in such a study. When
      parental information is non-randomly missing, due, for example, to death from the
      disease under study, the impact on type I error and power under dominant and
      recessive disease models has been reported. In this paper, we examine non
      ignorable missingness by assigning missing values to the genotypes of affected
      parents. We used unrelated case-parent trios in the Genetic Analysis Workshop 14
      simulated data for the Danacaa population. Our computer simulations revealed that
      the type I error of these tests using incomplete trios was not inflated over the
      nominal level under either recessive or dominant disease models. However, the
      power of these tests appears to be inflated over the complete information case
      due to an excess of heterozygous parents in dyads.

PMID- 16451707
TI  - The quantitative trait linkage disequilibrium test: a more powerful alternative
      to the quantitative transmission disequilibrium test for use in the absence of
      population stratification.
AB  - Linkage analysis based on identity-by-descent allele-sharing can be used to
      identify a chromosomal region harboring a quantitative trait locus (QTL), but
      lacks the resolution required for gene identification. Consequently, linkage
      disequilibrium (association) analysis is often employed for fine-mapping.
      Variance-components based combined linkage and association analysis for
      quantitative traits in sib pairs, in which association is modeled as a mean
      effect and linkage is modeled in the covariance structure has been extended to
      general pedigrees (quantitative transmission disequilibrium test, QTDT). The QTDT
      approach accommodates data not only from parents and siblings, but also from all
      available relatives. QTDT is also robust to population stratification. However,
      when population stratification is absent, it is possible to utilize even more
      information, namely the additional information contained in the founder
      genotypes. In this paper, we introduce a simple modification of the allelic
      transmission scoring method used in the QTDT that results in a more powerful test
      of linkage disequilibrium, but is only applicable in the absence of population
      stratification. This test, the quantitative trait linkage disequilibrium (QTLD)
      test, has been incorporated into a new procedure in the statistical genetics
      computer package SOLAR. We apply this procedure in a linkage/association analysis
      of an electrophysiological measurement previously shown to be related to
      alcoholism. We also demonstrate by simulation the increase in power obtained with
      the QTLD test, relative to the QTDT, when a true association exists between a
      marker and a QTL.

PMID- 16451708
TI  - Analysis of binary traits: testing association in the presence of linkage.
AB  - Most methods for testing association in the presence of linkage, using family
      based studies, have been developed for continuous traits. FBAT (family-based
      association tests) is one of few methods appropriate for discrete outcomes. In
      this article we describe a new test of association in the presence of linkage for
      binary traits. We use a gamma random effects model in which association and
      linkage are modelled as fixed effects and random effects, respectively. We have
      compared the gamma random effects model to an FBAT and a generalized estimating
      equation-based alternative, using two regions in the Genetic Analysis Workshop 14
      simulated data. One of these regions contained haplotypes associated with
      disease, and the other did not.

PMID- 16451709
TI  - Selection of single-nucleotide polymorphisms in disease association data.
AB  - We studied several methods for selecting single-nucleotide polymorphisms (SNPs)
      in a disease association study. Two major categories for analytical strategy are
      the univariate and the set selection approaches. The univariate approach
      evaluates each SNP marker one at a time, while the set selection approach tests
      disease association of a set of SNP markers simultaneously. We examined various
      test statistics that can be utilized in testing disease association and also
      reviewed several multiple testing procedures that can properly control the family
      wise error rates when the univariate approach is applied to multiple markers. The
      set association methods were then briefly reviewed. Finally, we applied these
      methods to the data from Collaborative Study on the Genetics of Alcoholism
      (COGA).

PMID- 16451710
TI  - Microsatellite linkage analysis, single-nucleotide polymorphisms, and haplotype
      associations with ECB21 in the COGA data.
AB  - This study, part of the Genetic Analysis Workshop 14 (GAW14), explored real
      Collaborative Study on the Genetics of Alcoholism data for linkage and
      association mapping between genetic polymorphisms (microsatellite and single
      nucleotide polymorphisms (SNPs)) and beta (16.5-20 Hz) oscillations of the brain
      rhythms (ecb21). The ecb21 phenotype underwent the statistical adjustments for
      the age of participants, and for attaining a normal distribution. A total of
      1,000 subjects' available phenotypes were included in linkage analysis with
      microsatellite markers. Linkage analysis was performed only for chromosome 4
      where a quantitative trait locus with 5.01 LOD score had been previously
      reported. Previous findings related this location with the gamma-aminobutyric
      acid type A (GABAA) receptor. At the same location, our analysis showed a LOD
      score of 2.2. This decrease in the LOD score is the result of a drastic reduction
      (one-third) of the available GAW14 phenotypic data. We performed SNP and
      haplotype association analyses with the same phenotypic data under the linkage
      peak region on chromosome 4. Seven Affymetrix and two Illumina SNPs showed
      significant associations with ecb21 phenotype. A haplotype, a combination of SNPs
      TSC0044171 and TSC0551006 (the latter almost under the region of GABAA genes),
      showed a significant association with ecb21 (p = 0.015) and a relatively high
      frequency in the sample studied. Our results affirmed that the GABA region has
      potential of harboring genes that contribute quantitatively to the beta
      oscillation of the brain rhythms. The inclusion of the remaining 614 subjects,
      which in the GAW14 had missing data for the ecb21, can improve the strength of
      the associations as they have already shown that they contribute quite important
      information in the linkage analysis.

PMID- 16451711
TI  - A regression based transmission/disequilibrium test for binary traits: the power
      of joint tests for linkage and association.
AB  - BACKGROUND: In this analysis we applied a regression based transmission
      disequilibrium test to the binary trait presence or absence of Kofendred
      Personality Disorder in the Genetic Analysis Workshop 14 (GAW14) simulated
      dataset and determined the power and type I error rate of the method at varying
      map densities and sample sizes. To conduct this transmission disequilibrium test,
      the logit transformation was applied to a binary outcome and regressed on an
      indicator variable for the transmitted allele from informative matings. All 100
      replicates from chromosomes 1, 3, 5, and 9 for the Aipotu and the combined
      Aipotu, Karangar, and Danacaa populations were used at densities of 3, 1, and 0.3
      cM. Power and type I error were determined by the number of replicates
      significant at the 0.05 level. RESULTS: The maximum power to detect linkage and
      association with the Aipotu population was 93% for chromosome 3 using a 0.3-cM
      map. For chromosomes 1, 5, and 9 the power was less than 10% at the 3-cM scan and
      less than 22% for the 0.3-cM map. With the larger sample size, power increased to
      38% for chromosome 1, 100% for chromosome 3, 31% for chromosome 5, and 23% for
      chromosome 9. Type I error was approximately 7%. CONCLUSION: The power of this
      method is highly dependent on the amount of information in a region. This study
      suggests that single-point methods are not particularly effective in narrowing a
      fine-mapping region, particularly when using single-nucleotide polymorphism data
      and when linkage disequilibrium in the region is variable.

PMID- 16451712
TI  - Comparison of linkage and association strategies for quantitative traits using
      the COGA dataset.
AB  - Genome scans using dense single-nucleotide polymorphism (SNP) data have recently
      become a reality. It is thought that the increase in information content for
      linkage analysis as a result of the denser scans will help refine previously
      identified linkage regions and possibly identify new regions not identifiable
      using the sparser, microsatellite scans. In the context of the dense SNP scans,
      it is also possible to consider association strategies to provide even more
      information about potential regions of interest. To circumvent the multiple
      testing issues inherent in association analysis, we use a recently developed
      strategy, implemented in PBAT, which screens the data to identify the optimal
      SNPs for testing, without biasing the nominal significance level. We compare the
      results from the PBAT analysis to that of quantitative linkage analysis on
      chromosome 4 using the Collaborative Study on the Genetics of Alcoholism data, as
      released through Genetic Analysis Workshop 14.

PMID- 16451713
TI  - Identifying genetic variation affecting a complex trait in simulated data: a
      comparison of meta-analysis with pooled data analysis.
AB  - We explored the power and consistency to detect linkage and association with meta
      analysis and pooled data analysis using Genetic Analysis Workshop 14 simulated
      data. The first 10 replicates from Aipotu population were used. Significant
      linkage and association was found at all 4 regions containing the major loci for
      Kofendrerd Personality Disorder (KPD) using both combined analyses although no
      significant linkage and association was found at all these regions in a single
      replicate. The linkage results from both analyses are consistent in terms of the
      significance level of linkage test and the estimate of locus location. After
      correction for multiple-testing, significant associations were detected for the
      same 8 single-nucleotide polymorphisms (SNP) in both analyses. There were another
      2 SNPs for which significant associations with KPD were found only by pooled data
      analysis. Our study showed that, under homogeneous condition, the results from
      meta-analysis and pooled data analysis are similar in both linkage and
      association studies and the loss of power is limited using meta-analysis. Thus,
      meta-analysis can provide an overall evaluation of linkage and association when
      the original raw data is not available for combining.

PMID- 16451714
TI  - Comparing strategies for association mapping in samples with related individuals.
AB  - In this paper, different strategies to test for association in samples with
      related individuals designed for linkage studies are compared. Because no
      independent controls are available, a family-based association test and case
      control tests corrected for the presence of related individuals in which
      unaffected relatives are used as controls were tested. When unrelated controls
      are available, additional strategies including selection of a single case per
      family considering either all families or a subset of linked families, are also
      considered. Analyses are performed on the simulated dataset, blind to the
      answers. The case-control test corrected for the presence of related individuals
      is the most powerful strategy to detect three loci associated with the disease
      under study. Using a correction factor for the case-control test performed
      conditional on the marker information rather than unconditional does not impact
      the power significantly.

PMID- 16451715
TI  - Using mixture models to characterize disease-related traits.
AB  - We consider 12 event-related potentials and one electroencephalogram measure as
      disease-related traits to compare alcohol-dependent individuals (cases) to
      unaffected individuals (controls). We use two approaches: 1) two-way analysis of
      variance (with sex and alcohol dependency as the factors), and 2) likelihood
      ratio tests comparing sex adjusted values of cases to controls assuming that
      within each group the trait has a 2 (or 3) component normal mixture distribution.
      In the second approach, we test the null hypothesis that the parameters of the
      mixtures are equal for the cases and controls. Based on the two-way analysis of
      variance, we find 1) males have significantly (p < 0.05) lower mean response
      values than females for 7 of these traits. 2) Alcohol-dependent cases have
      significantly lower mean response than controls for 3 traits. The mixture
      analysis of sex-adjusted values of 1 of these traits, the event-related potential
      obtained at the parietal midline channel (ttth4), found the appearance of a 3
      component normal mixture in cases and controls. The mixtures differed in that the
      cases had significantly lower mean values than controls and significantly
      different mixing proportions in 2 of the 3 components. Implications of this study
      are: 1) Sex needs to be taken into account when studying risk factors for alcohol
      dependency to prevent finding a spurious association between alcohol dependency
      and the risk factor. 2) Mixture analysis indicates that for the event-related
      potential "ttth4", the difference observed reflects strong evidence of
      heterogeneity of response in both the cases and controls.

PMID- 16451716
TI  - Diversity and utilization of antimalarial ethnophytotherapeutic remedies among
      the Kikuyus (Central Kenya).
AB  - Plants in Kenya are becoming increasingly important as sources of traditional
      medicines. The World Health Organization (WHO) has estimated that malaria kills
      about 2.7 million people every year, 90% of who are from Africa. Malaria
      continues to be a national concern in Kenya as it plays a major role in the high
      mortality rates being experienced currently. The use and mis-use of chloroquine
      to prevent and treat falciparium malaria has led to widespread appearance of
      chloroquine resistant parasites in Kenya and other tropical countries. These
      factors and the rising costs of non-chloroquine drugs have made the local people
      to turn to traditional remedies for management of this menace. This paper
      examines the current utilization of traditional plant medicines in managing
      malaria menace in Central Kenya. The results show both indigenous and introduced
      species are in use indicating traditional medicinal practices in this region are
      dynamic. In total 58 species in 54 genera and 33 families were identified. The
      family Rubiaceae was found to have the highest number of reported species. Use of
      the various taxa is compared between five districts within Central Province of
      Kenya. The commonest species in this pharmacopoeia are: Caesalpinia volkensii
      Harms, Strychnos henningsii Gilg, Ajuga remota Benth., Warbugia ugandensis
      Sprague and Olea europaea L. The first three species are used in all the five
      districts while the others are restricted in some of the districts. In 74% of the
      anti-malarial plant species reported in this study, the remedies are obtained in
      destructive manner and may need conservation measures to ensure sustainable
      utilization. The results of this study become a basis for selecting plants for
      further pharmacological and phytochemical studies in developing new and locally
      relevant anti-malarial agents.

PMID- 16451717
TI  - Injection drug use and HIV/AIDS in China: review of current situation, prevention
      and policy implications.
AB  - Illicit drug abuse and HIV/AIDS have increased rapidly in the past 10 to 20 years
      in China. This paper reviews drug abuse in China, the HIV/AIDS epidemic and its
      association with injection drug use (IDU), and Chinese policies on illicit drug
      abuse and prevention of HIV/AIDS based on published literature and unpublished
      official data. As a major drug trans-shipment country with source drugs from the
      "Golden Triangle" and "Gold Crescent" areas in Asia, China has also become an
      increasingly important drug consuming market. About half of China's 1.14 million
      documented drug users inject, and many share needles. IDU has contributed to 42%
      of cumulatively reported HIV/AIDS cases thus far. Drug trafficking is illegal in
      China and can lead to the death penalty. The public security departments adopt
      "zero tolerance" approach to drug use, which conflict with harm reduction
      policies of the public health departments. Past experience in China suggests that
      cracking down on drug smuggling and prohibiting drug use alone can not prevent or
      solve all illicit drug related problems in the era of globalization. In recent
      years, the central government has outlined a series of pragmatic policies to
      encourage harm reduction programs; meanwhile, some local governments have not
      fully mobilized to deal with drug abuse and HIV/AIDS problems seriously.
      Strengthening government leadership at both central and local levels; scaling up
      methadone substitution and needle exchange programs; making HIV voluntary
      counseling and testing available and affordable to both urban and rural drug
      users; and increasing utilization of outreach and nongovernmental organizations
      are offered as additional strategies to help cope with China's HIV and drug abuse
      problem.

PMID- 16451718
TI  - Progesterone improves the number and quality of hormone induced Fowler toad (Bufo
      fowleri) oocytes.
AB  - Combinations of progesterone, lutenizing hormone releasing hormone analogue
      (LHRHa), human chorionic gonadotrophin (hCG), and the dopamine-2 (DA2) receptor
      antagonist 1-[1-[4,4-bis(4-Fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-2H
      benzimidazol-2-one (Pimozide; Orap) were tested for improvement of spawning
      rates, oocyte numbers, fertilization and neurulation rates of the Fowler toad
      (Bufo fowleri). Only treatments combined with progesterone produced large numbers
      of oocytes. The best treatment on oocyte numbers, neurulation rates, and the
      number of neurulas was with 5 mg progesterone, 20 mic.g LHRHa, and 0.25 mg
      Pimozide. Progesterone (5 mg) with 60 mic.g LHRHa gave high spawning rates,
      oocyte numbers, and fertilization rates but neurulation rates were low.
      Progesterone alone in high repeated doses did not result in ovulation. High doses
      of LHRHa (60 mic.g) with hCG, progesterone, and Pimozide gave the greatest number
      of toads spawning, however, they resulted in low oocyte numbers, fertilization
      and neurulation rates. A low dose of LHRHa (4 mic.g) with hCG, or hCG alone as a
      second administration, and progesterone with Pimozide produced few good quality
      oocytes. Toads were given normal ovulatory doses of hormones 24 or 48 hrs after
      their initial dose, but these resulted in low oocyte numbers followed by poor
      fertilization. Overall, these results suggest that progesterone with a dose
      between 20 mic.g and 60 mic.g of LHRHa may be optimal for the induction of
      ovulation in these toads. Moreover, Pimozide can supplement low doses of LHRHa
      but not replace it.

PMID- 16451719
TI  - Personality preference influences medical student use of specific computer-aided
      instruction (CAI).
AB  - BACKGROUND: The objective of this study was to test the hypothesis that
      personality preference, which can be related to learning style, influences
      individual utilization of CAI applications developed specifically for the
      undergraduate medical curriculum. METHODS: Personality preferences of students
      were obtained using the Myers-Briggs Type Indicator (MBTI) test. CAI utilization
      for individual students was collected from entry logs for two different web-based
      applications (a discussion forum and a tutorial) used in the basic science course
      on human anatomy. Individual login data were sorted by personality preference and
      the data statistically analyzed by 2-way mixed ANOVA and correlation. RESULTS:
      There was a wide discrepancy in the level and pattern of student use of both CAI.
      Although individual use of both CAI was positively correlated irrespective of
      MBTI preference, students with a "Sensing" preference tended to use both CAI
      applications more than the "iNtuitives". Differences in the level of use of these
      CAI applications (i.e., higher use of discussion forum vs. a tutorial) were also
      found for the "Perceiving/Judging" dimension. CONCLUSION: We conclude that
      personality/learning preferences of individual students influence their use of
      CAI in the medical curriculum.

PMID- 16451720
TI  - A survey of factors affecting clinician acceptance of clinical decision support.
AB  - BACKGROUND: Real-time clinical decision support (CDS) integrated into clinicians'
      workflow has the potential to profoundly affect the cost, quality, and safety of
      health care delivery. Recent reports have identified a surprisingly low
      acceptance rate for different types of CDS. We hypothesized that factors
      affecting CDS system acceptance could be categorized as relating to differences
      in patients, physicians, CDS-type, or environmental characteristics. METHODS: We
      conducted a survey of all adult primary care physicians (PCPs, n = 225) within
      our group model Health Maintenance Organization (HMO) to identify factors that
      affect their acceptance of CDS. We defined clinical decision support broadly as
      "clinical information" that is either provided to you or accessible by you, from
      the clinical workstation (e.g., enhanced flow sheet displays, health maintenance
      reminders, alternative medication suggestions, order sets, alerts, and access to
      any internet-based information resources). RESULTS: 110 surveys were returned
      (49%). There were no differences in the age, gender, or years of service between
      those who returned the survey and the entire adult PCP population. Overall,
      clinicians stated that the CDS provided "helps them take better care of their
      patients" (3.6 on scale of 1:Never-5:Always), "is worth the time it takes" (3.5),
      and "reminds them of something they've forgotten" (3.2). There was no difference
      in the perceived acceptance rate of alerts based on their type (i.e., cost,
      safety, health maintenance). When asked about specific patient characteristics
      that would make the clinicians "more", "equally" or "less" likely to accept
      alerts: 41% stated that they were more (8% stated "less") likely to accept alerts
      on elderly patients (> 65 yrs); 38% were more (14% stated less) likely to accept
      alerts on patients with more than 5 current medications; and 38% were more (20%
      stated less) likely to accept alerts on patients with more than 5 chronic
      clinical conditions. Interestingly, 80% said they were less likely to accept
      alerts when they were behind schedule and 84% of clinicians admitted to being at
      least 20 minutes behind schedule "some", "most", or "all of the time".
      CONCLUSION: Even though a majority of our clinical decision support suggestions
      are not explicitly followed, clinicians feel they are of benefit and would be
      even more beneficial if they had more time available to address them.

PMID- 16451721
TI  - Epstein-barr virus induced cellular changes in nasal mucosa.
AB  - A 21-year-old man presented with nasal obstruction of the right nasal fossa of 1
      year duration. Nasal endoscopy revealed in the right inferior turbinate head a
      rounded neoplasm about 1 cm in diameter. Cytologic study of a nasal scraping
      specimen disclosed numerous clusters containing columnar cells with cytomegaly,
      prominent multinucleation, markedly sparse shortened cilia; the cytoplasm
      contained an acidophil area and a small round area that stained poorly; cells
      with a large intracytoplasmic vacuole that was acidophil and PAS+. Serology tests
      using the nested polymer chain reaction (PCR) technique on serum, nasal and
      pharyngeal smears revealed an Epstein-Barr virus (EBV) infection that was
      confirmed at electron microscopy. The clinical and cytological features resolved
      19 months after the initial evaluation. CONCLUSION: The authors advise carrying
      out clinical (endoscopy, serology, etc.) evaluation of all endonasal neoplasms
      and to routinely perform cytological study on nasal scraping specimens. When
      samples test positive for EBV, nasal and nasopharyngeal endoscopy should be
      performed regularly to detect possible evidence for nasopharyngeal carcinoma
      (NPC).

PMID- 16451722
TI  - Analysis of air pollution mortality in terms of life expectancy changes: relation
      between time series, intervention, and cohort studies.
AB  - BACKGROUND: Information on life expectancy change is of great concern for policy
      makers, as evidenced by the discussions of the so-called "harvesting" issue (i.e.
      the question being, how large a loss each death corresponds to in the mortality
      results of time series studies). METHODS: Whereas most epidemiological studies of
      air pollution mortality have been formulated in terms of mortality risk, this
      paper shows that a formulation in terms of life expectancy change is
      mathematically equivalent, but offers several advantages: it automatically takes
      into account the constraint that everybody dies exactly once, regardless of
      pollution; it provides a unified framework for time series, intervention studies
      and cohort studies; and in time series and intervention studies, it yields the
      life expectancy change directly as a time integral of the observed mortality
      rate. RESULTS: Results are presented for life expectancy change in time series
      studies. Determination of the corresponding total number of attributable deaths
      (as opposed to the number of observed deaths) is shown to be problematic. The
      time variation of mortality after a change in exposure is shown to depend on the
      processes by which the body can repair air pollution damage, in particular on
      their time constants. Hypothetical results are presented for repair models that
      are plausible in view of the available intervention studies of air pollution and
      of smoking cessation. If these repair models can also be assumed for acute
      effects, the results of cohort studies are compatible with those of time series.
      CONCLUSION: The proposed life expectancy framework provides information on the
      life expectancy change in time series studies, and it clarifies the relation
      between the results of time series, intervention, and cohort studies.

PMID- 16451723
TI  - Kenyan medicinal plants used as antivenin: a comparison of plant usage.
AB  - The success of snake bite healers is vaguely understood in Kenya, partly due to
      their unknown materia medica and occult-mystical nature of their practice. A
      comparison is made of plants used in snake bite treatments by two culturally
      distinct African groups (the Kamba and Luo). Thirty two plants used for snakebite
      treatment are documented. The majority of the antidotes are prepared from freshly
      collected plant material - frequently leaves. Though knowledge of snake bite
      conditions etiological perceptions of the ethnic groups is similar, field
      ethnobotanical data suggests that plant species used by the two ethnic groups are
      independently derived. Antivenin medicinal plants effectively illustrate the
      cultural context of medicine. Randomness or the use of a variety of species in
      different families appears to be a feature of traditional snake bite treatments.
      A high degree of informant consensus for the species was observed. The study
      indicates rural Kenya inhabitants rely on medicinal plants for healthcare.

PMID- 16451724
TI  - Apgar score and hospitalization for epilepsy in childhood: a registry-based
      cohort study.
AB  - BACKGROUND: A depressed Apgar score at 5 minutes is a marker for perinatal
      insults, including neurologic damage. We examined the association between 5
      minute Apgar score and the risk of epilepsy hospitalization in childhood.
      METHODS: Using records linked from population registries, we conducted a cohort
      study among singleton children born alive in the period 1978-2001 in North
      Jutland County, Denmark. The first hospital discharge diagnosis of epilepsy
      during the follow-up time was the main outcome. We followed each child for up to
      12 years, calculated absolute risks and risk differences, and used a Poisson
      regression model to estimate risk ratios for epilepsy hospitalization. We
      adjusted risk ratio estimates for birth weight, gestational age, mode of
      delivery, birth presentation, mother's age at delivery, and birth defects.
      RESULTS: One percent of the 131,853 eligible newborns had a 5-minute Apgar score
      <7. These children were more likely to be hospitalized with epilepsy during the
      follow-up than were children with an Apgar score of 7 or greater. The crude risk
      difference for epilepsy hospitalization was 2.5 cases per 100 (95% confidence
      interval [CI] 1.3 to 3.8). The risk difference estimates were greater in the
      presence of other perinatal risk factors. The adjusted risk ratio was 2.4 (95% CI
      1.5 to 3.8). Half of the 12-year risk for epilepsy hospitalization in those with
      a depressed Apgar score occurred during the first year of life. The risk ratio
      during the first year of life was 4.9 (95% CI 2.0 to 12.3). CONCLUSION: An Apgar
      score <7 at five minutes predicts an increase in the subsequent risk of epilepsy
      hospitalization. This association is amplified by other perinatal risk factors.

PMID- 16451725
TI  - Assessing stability of gene selection in microarray data analysis.
AB  - BACKGROUND: The number of genes declared differentially expressed is a random
      variable and its variability can be assessed by resampling techniques. Another
      important stability indicator is the frequency with which a given gene is
      selected across subsamples. We have conducted studies to assess stability and
      some other properties of several gene selection procedures with biological and
      simulated data. RESULTS: Using resampling techniques we have found that some
      genes are selected much less frequently (across sub-samples) than other genes
      with the same adjusted p-values. The extent to which this type of instability
      manifests itself can be assessed by a method introduced in this paper. The effect
      of correlation between gene expression levels on the performance of multiple
      testing procedures is studied by computer simulations. CONCLUSION: Resampling
      represents a tool for reducing the set of initially selected genes to those with
      a sufficiently high selection frequency. Using resampling techniques it is also
      possible to assess variability of different performance indicators. Stability
      properties of several multiple testing procedures are described at length in the
      present paper.

PMID- 16451726
TI  - The relationship between stage 1 and 2 non-small cell lung cancer and lung
      function in men and women.
AB  - BACKGROUND: Reduced forced expiratory volume in one second (FEV1) has been linked
      to non small cell lung cancer (NSCLC). However, it is unclear whether all or only
      certain histological subtypes of NSCLC are associated with reduced FEV1.
      Moreover, there is little information on whether gender modifies this
      relationship. Using a large tissue registry, we sought to determine the
      relationship between FEV1 and subtypes of NSCLC and determine whether this
      relationship is modified by gender. METHODS: We used data from patients who
      underwent tumor resection for NSCLC at a teaching hospital in Vancouver and had
      various pre-operative clinical measurements including FEV1. We divided the cohort
      into quartiles of predicted FEV1 and using both logistic and linear regression
      modeling techniques determined whether FEV1 was related to the occurrence of
      adeno or squamous cell carcinoma in men and women. RESULTS: There were 610
      patients in the study (36% females). On average, women were more likely to have
      adenocarcinoma than were men (72% of all cases of NSCLC in women versus 40% in
      men; p < 0.001). In women, there was no significant relationship between FEV1 and
      the risk of any histological subtypes of NSCLC. In men, however, there was an
      inverse relationship between the risk of adenocarcinoma and FEV1 such that the
      lowest quartile of FEV1 was 47% less likely to have adenocarcinoma compared with
      the highest FEV1 quartile (adjusted odds ratio, 0.52; 0.28 to 0.98; p for trend,
      0.028). The reverse was observed for squamous cell carcinoma. CONCLUSION: In
      individuals undergoing lung resection for NSCLC, the risk of adenocarcinoma and
      squamous cell carcinoma of the lung varies as a function of FEV1, independent of
      smoking intensity in men but not in women. CLINICAL IMPLICATIONS: These data
      indicate that women are much more susceptible to adenocarcinoma than are men
      especially when they have normal or near normal lung function. It may thus be
      useful to conduct periodic surveillance chest radiographs in asymptomatic female
      smokers (or ex-smokers) to ascertain peripheral nodules or masses before distant
      metastases occur since adenocarcinomas tend to metastasize earlier in the disease
      course than squamous cell carcinomas.

PMID- 16451727
TI  - Massive empyema caused by Mycoplasma pneumoniae in an adult: a case report.
AB  - BACKGROUND: Mycoplasma pneumoniae is responsible for more than 20% of community
      acquired pneumonia cases, and capable of causing upper respiratory illness as
      well. Complications of M.pneumoniae infections include CNS involvement but other
      as pericarditis were also reported. The lack of feasible culture methods and
      under appreciation of the pathogens ability to cause invasive disease leads to
      reduced number of diagnosed M.pneumoniae related complications. In contrast to
      many other respiratory pathogens causing pneumonia, M. pneumoniae related severe
      pleural complications were almost never reported. CASE PRESENTATION: We report a
      previously healthy 57 years old woman presented with indolent massive right
      pleural effusion, leukocytosis and elevated ESR. Extensive microbiological
      evaluation didn't reveal any pathogen in the pus even before antibiotic treatment
      was started. Surprisingly, M.pneumoniae DNA was detected in the pus from the
      empyema using PCR designed to detect M.pneumoniae. A serological assay (Serodia
      Myco II) using convalescent serum was indeterminate with a titer of 1:80. The
      patient responded well to a treatment that included right thoracotomy with
      pleural decortication and a combination of antibiotics and anti-inflammatory
      medications. CONCLUSION: M.pneumoniae related empyema was never reported before
      in adult patients and was reported in only a few pediatric patients. In our
      patient there was no evidence to any common pathogens even before initiating
      antibiotic treatment. The only pathogen detected was M.pneumoniae. In this
      patient, serology was not helpful in establishing the diagnosis of M.pneumoniae
      related diseases, as was suggested before for older patients. We suggest that
      M.pneumoniae related empyema is probably under-diagnosed complication due to
      insensitivity of serology in older patients and under use of other diagnosis
      methods.

PMID- 16451728
TI  - Malaria prophylaxis policy for travellers from Europe to the Indian Subcontinent.
AB  - Analysis of malaria imported into eight European countries from the Indian Sub
      continent (ISC) (India, Pakistan, Bangladesh and Sri Lanka) led to a consensus
      statement on the use of chemoprophylaxis within TropNetEurop. The proportion of
      cases from the ISC in 2004 ranged from 1.4%-4.6% of total imported cases.
      Plasmodium falciparum cases reported from the eight countries was only 23 (13% of
      all cases from the region). Total malaria reports between 1999-2004 fell from 317
      to 180. The risk of malaria in UK residents visiting the region was > 1 case per
      1,000 years exposed. The group recommended non-selective prescribing of
      chemoprophylaxis for visitors to India, Pakistan, Bangladesh and Sri Lanka should
      be dropped.

PMID- 16451730
TI  - A non-randomised, single-centre comparison of induction chemotherapy followed by
      radiochemotherapy versus concomitant chemotherapy with hyperfractionated
      radiotherapy in inoperable head and neck carcinomas.
AB  - BACKGROUND: The application of induction chemotherapy failed to provide a
      consistent benefit for local control in primary treatment of advanced head and
      neck (H&N) cancers. The aim of this study was to compare the results of
      concomitant application of radiochemotherapy for treating locally advanced head
      and-neck carcinoma in comparison with the former standard of sequential
      radiochemotherapy. METHODS: Between 1987 and 1995 we treated 122 patients with
      unresectable (stage IV head and neck) cancer by two different protocols. The
      sequential protocol (SEQ; 1987-1992) started with two courses of neoadjuvant
      chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic
      acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy
      using conventional fractionation up to 70 Gy. The concomitant protocol (CON;
      since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC)
      concomitantly with a course of radiotherapy up to 30 Gy in conventional
      fractionation, followed by a hyperfractionated course up to 72 Gy. Results from
      the two groups were compared. RESULTS: Patient and tumor characteristics were
      balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs.
      71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local
      control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group,
      revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08)
      and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis
      grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was
      similar in both groups. CONCLUSION: Concurrent chemotherapy seemed more effective
      in treating head and neck tumors than induction chemotherapy followed by
      chemoradiation, resulting in better local control and a trend towards improved
      survival.

PMID- 16451729
TI  - Housing conditions and Plasmodium falciparum infection: protective effect of iron
      sheet roofed houses.
AB  - BACKGROUND: Identification and better understanding of potential risk factors for
      malaria are important for targeted and cost-effective health interventions.
      Housing conditions have been suggested as one of the potential risk factors. This
      study aims to further investigate this risk factor, and is focused on the effect
      of the type of roof on Plasmodium falciparum infection among children below five
      years in the North West of Burkina Faso. METHODS: In a cross-sectional study
      design, 661 children aged six to 60 months were randomly selected from three
      rural and one semi-urban site at the end of the rainy season (November 2003). The
      children were screened for fever and tested for Plasmodium falciparum infection.
      In addition, data on bed net use and house characteristics was collected from the
      household were each child lived. Using adjusted odds ratios, children living in
      house roofed with iron-sheet were compared with those in house with mud or grass
      roof. RESULTS: Overall P. falciparum infection prevalence was 22.8 % with a
      significant variation between (Chi-square, p < 0.0001). The prevalence in Cisse
      (33.3 %) and Goni (30.6 %) were twice times more than in Nouna (15.2 %) and
      Kodougou (13.2 %). After adjusting for age, sex, use of bed net and housing
      conditions, children living in houses with mud roofs had significantly higher
      risk of getting P. falciparum infection compared to those living in iron-sheet
      roofed houses (Odds Ratio 2.6; 95% Confidence Interval, 1.4-4.7). CONCLUSION:
      These results suggest that house characteristics should be taken into
      consideration when designing health intervention against P. falciparum infection
      and particular attention should be paid to children living in houses with mud
      roofs.

PMID- 16451731
TI  - Field evaluation of a rapid immunochromatographic dipstick test for the diagnosis
      of cholera in a high-risk population.
AB  - BACKGROUND: Early detection of cholera outbreaks is crucial for the
      implementation of the most appropriate control strategies. METHODS: The
      performance of an immunochromatographic dipstick test (Institute Pasteur, Paris,
      France) specific for Vibrio cholerae O1 was evaluated in a prospective study in
      Beira, Mozambique, during the 2004 cholera season (January-May). Fecal specimens
      were collected from 391 patients with acute watery nonbloody diarrhea and tested
      by dipstick and conventional culture. RESULTS: The overall sensitivity and
      specificity of the rapid test compared to culture were 95% (95% confidence
      interval [CI]: 91%-99%) and 89% (95% CI: 86%-93%), respectively. After
      stratification by type of sample (rectal swab/bulk stool) and severity of
      diarrhea, the sensitivity ranged between 85% and 98% and specificity between 77%
      and 97%. CONCLUSION: This one-step dipstick test performed well in the diagnosis
      of V. cholerae O1 in a setting with seasonal outbreaks where rapid tests are most
      urgently needed.

PMID- 16451732
TI  - Influences of obese (ob/ob) and diabetes (db/db) genotype mutations on lumber
      vertebral radiological and morphometric indices: skeletal deformation associated
      with dysregulated systemic glucometabolism.
AB  - BACKGROUND: Both diabetes and obesity syndromes are recognized to promote lumbar
      vertebral instability, premature osteodegeneration, exacerbate progressive
      osteoporosis and increase the propensity towards vertebral degeneration,
      instability and deformation in humans. METHODS: The influences of single-gene
      missense mutations, expressing either diabetes (db/db) or obese (ob/ob) metabolic
      syndromes on vertebral maturation and development in C57BL/KsJ mice were
      evaluated by radiological and macro-morphometric analysis of the resulting
      variances in osteodevelopment indices relative to control parameters between 8
      and 16 weeks of age (syndrome onset @ 4 weeks), and the influences of low-dose 17
      B-estradiol therapy on vertebral growth expression evaluated. RESULTS: Associated
      with the indicative genotypic obesity and hyper-glycemic/-insulinemic states,
      both db/db and ob/ob mutants demonstrated a significant (P < or = 0.05)
      elongation of total lumbar vertebrae column (VC) regional length, and individual
      lumbar vertebrae (LV1-5) lengths, relative to control VC and LV parameters. In
      contrast, LV1-5 width indices were suppressed in db/db and ob/ob mutants relative
      to control LV growth rates. Between 8 and 16 weeks of age, the suppressed LV1-5
      width indices were sustained in both genotype mutant groups relative to control
      osteomaturation rates. The severity of LV1-5 width osteosuppression correlated
      with the severe systemic hyperglycemic and hypertriglyceridemic conditions
      sustained in ob/ob and db/db mutants. Low-dose 17-B-estradiol therapy (E2-HRx:
      1.0 ug/ 0.1 ml oil s.c/3.5 days), initiated at 4 weeks of age (i.e., initial
      onset phase of db/db and ob/ob expressions) re-established control LV 1-5 width
      indices without influencing VC or LV lengths in db/db groups. CONCLUSION: These
      data demonstrate that the abnormal systemic endometabolic states associated with
      the expression of db/db and ob/ob genomutation syndromes suppress LV 1-5 width
      osteomaturation rates, but enhanced development related VC and LV length
      expression, relative to control indices in a progressive manner similar to
      recognized human metabolic syndrome conditions. Therapeutic E2 modulation of the
      hyperglycemic component of diabetes-obesity syndrome protected the regional LV
      from the mutation-induced osteopenic width-growth suppression. These data suggest
      that these genotype mutation models may prove valuable for the evaluation of
      therapeutic methodologies suitable for the treatment of human diabetes- or
      obesity-influenced, LV degeneration-linked human conditions, which demonstrate
      amelioration from conventional replacement therapies following diagnosis of
      systemic syndrome-induced LV osteomaturation-associated deformations.

PMID- 16451733
TI  - D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D
      MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells.
AB  - BACKGROUND: The family of c-Jun NH2-terminal kinases (JNK) plays important roles
      in embryonic development and in cellular responses to stress. Toxic metals and
      their compounds are potent activators of JNK in mammalian cells. The mechanism of
      mammalian JNK activation by cadmium and sodium arsenite involves toxicant-induced
      oxidative stress. The study of mammalian signaling pathways to JNK is complicated
      by the significant degree of redundancy among upstream JNK regulators, especially
      at the level of JNK kinase kinases (JNKKK). RESULTS: Using Drosophila
      melanogaster S2 cells, we demonstrate here that cadmium and arsenite activate
      Drosophila JNK (D-JNK) via oxidative stress as well, thus providing a simpler
      model system to study JNK signaling. To elucidate the signaling pathways that
      lead to activation of D-JNK in response to cadmium or arsenite, we employed RNA
      interference (RNAi) to knock down thirteen upstream regulators of D-JNK, either
      singly or in combinations of up to seven at a time. CONCLUSION: D-MEKK1, the fly
      orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediates the
      activation of D-JNK by cadmium and arsenite.

PMID- 16451734
TI  - A novel cell immunoassay to measure survival of motor neurons protein in blood
      cells.
AB  - BACKGROUND: The motor neuron degenerative disease spinal muscular atrophy (SMA)
      is the leading genetic cause of infant mortality and is caused by mutations in
      the survival of motor neurons (SMN) gene that reduce the expression levels of the
      SMN protein. A major goal of current therapeutic approaches is to increase SMN
      levels in SMA patients. The purpose of this study was to develop a reliable assay
      to measure SMN protein levels from peripheral blood samples. METHODS: We
      developed a novel cell immunoassay to quantitatively measure SMN levels from
      peripheral blood mononuclear cells (PBMCs) using a single anti-SMN antibody.
      RESULTS: SMN levels determined by the cell immunoassay are comparable to levels
      determined by Western blot, but in contrast, the immunoassay does not involve
      cell lysis, requires a small amount of patient material, and can be done on a
      large number of samples simultaneously. SMN levels from PBMCs are not influenced
      by cell type heterogeneity. CONCLUSION: SMN levels measured from total PBMCs
      provide an important snapshot of SMN protein expression, which should be a useful
      aid in SMA diagnosis, and a surrogate marker of efficacy of treatment in SMA
      clinical trials.

PMID- 16451735
TI  - Thrombocytopenia in the experimental leptospirosis of guinea pig is not related
      to disseminated intravascular coagulation.
AB  - BACKGROUND: Thrombocytopenia is commonly observed in severe leptospirosis.
      However, previous studies on coagulation alterations during leptospirosis
      resulted in inconsistent conclusions. Some findings showed that the prominent
      levels of thrombocytopenia observed in severe leptospirosis did not reflect the
      occurrence of disseminated intravascular coagulation (DIC) syndrome, while the
      others reached the conclusion that the hemorrhages observed in leptospirosis were
      due to DIC. The aim of this study is to elucidate whether DIC is an important
      feature of leptospirosis. METHODS: The leptospirosis model of guinea pig was
      established by intraperitoneal inoculation of Leptospira interrogans strain Lai.
      Hematoxylin and eosin (HE) staining, electron microscopy and immunohistochemistry
      staining were used to detect the pathologic changes. Platelet thrombus or fibrin
      thrombus was detected by HE, Martius Scarlet Blue (MSB) staining and electron
      microscopy. Hemostatic molecular markers such as 11-dehydrogenate thromboxane B2
      (11-DH-TXB2), thrombomodulin (TM), thrombin-antithrombin III complex (TAT), D
      Dimer and fibrin (ogen) degradation products (FDPs) in the plasma were examined
      by quantitative enzyme-linked immunosorbent assay (ELISA) to evaluate the
      hematological coagulative alterations in leptospirosis models. RESULTS: Pulmonary
      hemorrhage appeared in the model guinea pig 24 hours after leptospires
      intraperitoneal inoculation, progressing to a peak at 96 hours after the
      infection. Leptospires were detected 24 hours post-inoculation in the liver, 48
      hours in the lung and 72 hours in the kidney by immunohistochemistry staining.
      Spiral form of the bacteria was initially observed in the liver, lung and kidney
      suggestive of intact leptospires, granular form of leptospires was seen as the
      severity increased. Platelet aggregation in hepatic sinusoid as well as
      phagocytosis of erythrocytes and platelets by Kupffer cells were both observed.
      Neither platelet thrombus nor fibrin thrombus was found in the liver, lung or
      kidney via morphological observation. Thrombocytopenia was observed in all
      infected guinea pigs of our experimental leptospirosis study. Analysis of
      hematologic molecular markers showed that 11-DH-TXB2 and TM in the plasma were
      elevated significantly. TAT that reflects the thrombin activation had a trend of
      decline after infection. Although D-dimer and FDPs increased statistically, the
      increasing may not bear clinical significance. CONCLUSION: Pathologic and
      hematological studies for experimental leptospirosis of guinea pig indicated that
      the thrombocytopenia found in guinea pigs did not correlate with the occurrence
      of DIC. The platelet aggregation and Kupffer cells phagocytosis might be the
      potential causes of thrombocytopenia in severe leptospirosis.

PMID- 16451736
TI  - Combined immunohistochemistry of beta-catenin, cytokeratin 7, and cytokeratin 20
      is useful in discriminating primary lung adenocarcinomas from metastatic
      colorectal cancer.
AB  - BACKGROUND: It is important to discriminate between primary and secondary lung
      cancer. However, often, the discriminating diagnosis of primary lung acinar
      adenocarcinoma and lung metastasis of colorectal cancer based on morphological
      and pathological findings is difficult. The purpose of this study was to evaluate
      the clinical usefulness of immunohistochemistry of beta-catenin, cytokeratin (CK)
      7, and CK20 for the discriminating diagnosis of lung cancer. METHODS: We
      performed immunohistochemistry of beta-catenin, CK7, and CK20 in 19 lung
      metastasis of colorectal cancer samples, 10 corresponding primary colorectal
      cancer samples and 11 primary lung acinar adenocarcinoma samples and compared the
      levels of accuracy of the discriminating diagnosis by using antibodies against
      these antigens. RESULTS: Positive staining of beta-catenin was observed in all
      the lung metastasis of colorectal cancer samples as well as in the primary
      colorectal cancer samples but in none of the primary lung acinar adenocarcinoma
      samples. Positive staining of CK7 was observed in 90.9% of the primary lung
      acinar adenocarcinoma samples and in 5.3% of the lung metastasis of colorectal
      cancer samples, but in none of the primary colorectal cancer samples. Positive
      staining of CK20 was observed in all the primary colorectal cancer samples and in
      84.2% of the lung metastasis of colorectal cancer samples, but in none of the
      primary lung acinar adenocarcinoma samples. CONCLUSION: Combined
      immunohistochemistry of beta-catenin, CK7, and CK20 is useful for making a
      discriminating diagnosis between lung metastasis of colorectal cancer and primary
      lung acinar adenocarcinoma. This method will enable accurate diagnosis of a lung
      tumor and will be useful for selecting appropriate therapeutic strategies,
      including chemotherapeutic agents and operation methods.

PMID- 16451737
TI  - Detection of compound mode of action by computational integration of whole-genome
      measurements and genetic perturbations.
AB  - BACKGROUND: A key problem of drug development is to decide which compounds to
      evaluate further in expensive clinical trials (Phase I- III). This decision is
      primarily based on the primary targets and mechanisms of action of the chemical
      compounds under consideration. Whole-genome expression measurements have shown to
      be useful for this process but current approaches suffer from requiring either a
      large number of mutant experiments or a detailed understanding of the regulatory
      networks. RESULTS: We have designed an algorithm, CutTree that when applied to
      whole-genome expression datasets identifies the primary affected genes (PAGs) of
      a chemical compound by separating them from downstream, indirectly affected
      genes. Unlike previous methods requiring whole-genome deletion libraries or a
      complete map of gene network architecture, CutTree identifies PAGs from a limited
      set of experimental perturbations without requiring any prior information about
      the underlying pathways. The principle for CutTree is to iteratively filter out
      PAGs from other recurrently active genes (RAGs) that are not PAGs. The in silico
      validation predicted that CutTree should be able to identify 3-4 out of 5 known
      PAGs (approximately 70%). In accordance, when we applied CutTree to whole-genome
      expression profiles from 17 genetic perturbations in the presence of galactose in
      Yeast, CutTree identified four out of five known primary galactose targets (80%).
      Using an exhaustive search strategy to detect these PAGs would not have been
      feasible (>1012 combinations). CONCLUSION: In combination with genetic
      perturbation techniques like short interfering RNA (siRNA) followed by whole
      genome expression measurements, CutTree sets the stage for compound target
      identification in less well-characterized but more disease-relevant mammalian
      cell systems.

PMID- 16451742
TI  - In-vitro and in-vivo assays for angiogenesis-modulating drug discovery and
      development.
AB  - In the past 35 years, significant findings have been made in relation to
      angiogenesis, and how this usually normal physiological function is converted
      into an abnormal state in cancer. To search for agents that can inhibit
      angiogenesis, and thereby prevent a tumour from proliferation and spread that is
      ultimately fatal to the patient, various in-vitro assays have been developed. In
      addition, older assays have been refined usually into high throughput screening
      formats, mainly by the biopharmaceutical industry in their attempts to develop
      novel therapeutic molecules and maintain a pipeline of lead candidates. The
      central aim is to extract more accurate data that would facilitate the birth of
      innovative mechanisms to defeat aberrant angiogenesis in-vivo. At the same time,
      better in-vivo models have been established, with the goal to mimic as close as
      possible the natural progression of various types of neoplasms in response to a
      good angiogenic response. More clinically relevant models are needed as anti
      angiogenesis drug discovery and drug development companies fast track their lead
      molecules from preclinical investigations to phase I clinical trials.

PMID- 16451739
TI  - A review of the correlation of tergites, sternites, and leg pairs in diplopods.
AB  - In some arthropods there is a discrepancy in the number of dorsal tergites
      compared to the number of ventral sternites and leg pairs. The posterior tergites
      of the Diplopoda (millipedes) each cover two sternites and two pairs of legs.
      This segment arrangement is called diplosegmentation. The molecular nature of
      diplosegmentation is still unknown. There are even conflicting theories on the
      way the tergites and sternites/leg pairs should be correlated to each other. The
      different theories are based either on embryological analyses or on studies of
      the adult morphology and turned out to be not compatible with each other. We have
      previously used the expression patterns of segmentation genes in the pill
      millipede Glomeris marginata (Myriapoda: Diplopoda) to study millipede
      segmentation. Here we review the existing models on the alignment of tergites and
      leg pairs in millipedes with special emphasis on the implications the gene
      expression data have on the debate of tergite and leg pair assignment in
      millipedes. The remarkable outcome of the gene expression analysis was that (1)
      there is no coupling of dorsal and ventral segmentation and, importantly, that
      (2) the boundaries delimiting the tergites do neither correlate to the embryonic
      boundaries of the dorsal embryonic segments nor to the boundaries of the ventral
      embryonic segments. Using these new insights, we critically reinvestigated the
      correlation of tergites, sternites, and leg pairs in millipedes. Our model, which
      takes into account that the tergite boundaries are different from the dorsal
      embryonic segment boundaries, provides a solution of the problem of tergite to
      sternite/leg pair correlation in basal milipedes with non-fused exoskeletal
      elements and also has implications for derived species with exoskeletal rings.
      Moreover, lack of coupling of dorsal and ventral segmentation may also explain
      the discrepancy in numbers of dorsal tergites and ventral leg pairs seen in some
      other arthropods.

PMID- 16451738
TI  - NADPH- diaphorase positive cardiac neurons in the atria of mice. A
      morphoquantitative study.
AB  - BACKGROUND: The present study was conducted to determine the location, the
      morphology and distribution of NADPH-diaphorase positive neurons in the cardiac
      nerve plexus of the atria of mice (ASn). This plexus lies over the muscular layer
      of the atria, dorsal to the muscle itself, in the connective tissue of the
      subepicardium. NADPH- diaphorase staining was performed on whole-mount
      preparations of the atria mice. For descriptive purposes, all data are presented
      as means +/- SEM. RESULTS: The majority of the NADPH-diaphorase positive neurons
      were observed in the ganglia of the plexus. A few single neurons were also
      observed. The number of NADPH-d positive neurons was 57 +/- 4 (ranging from 39 to
      79 neurons). The ganglion neurons were located in 3 distinct groups: (1) in the
      region situated cranial to the pulmonary veins, (2) caudally to the pulmonary
      veins, and (3) in the atrial groove. The largest group of neurons was located
      cranially to the pulmonary veins (66.7%). Three morphological types of NADPH
      diaphorase neurons could be distinguished on the basis of their shape: unipolar
      cells, bipolar cells and cells with three processes (multipolar cells). The
      unipolar neurons predominated (78.9%), whereas the multipolar were encountered
      less frequently (5,3%). The sizes (area of maximal cell profile) of the neurons
      ranged from about 90 microm2 to about 220 microm2. Morphometrically, the three
      types of neurons were similar and there were no significant differences in their
      sizes. The total number of cardiac neurons (obtained by staining the neurons with
      NADH-diaphorase method) was 530 +/- 23. Therefore, the NADPH-diaphorase positive
      neurons of the heart represent 10% of the number of cardiac neurons stained by
      NADH. CONCLUSION: The obtained data have shown that the NADPH-d positive neurons
      in the cardiac plexus of the atria of mice are morphologically different, and
      therefore, it is possible that the function of the neurons may also be different.

PMID- 16451743
TI  - Skin permeation of retinol in Tween 20-based deformable liposomes: in-vitro
      evaluation in human skin and keratinocyte models.
AB  - To develop a more effective transdermal delivery method for lipophilic functional
      cosmetic compounds such as retinol, we formulated various deformable liposomes
      and compared their transdermal delivery efficiency with those of neutral or
      negatively-charged conventional liposomes. We tested the deformability of
      liposomes containing edge activators such as bile salts, polyoxyethylene esters
      and polyoxyethylene ethers. As indicators of deformability, we used the passed
      volume and phospholipid ratios during extrusion, as well as the deformability
      index. We found that the type of edge activator significantly affected the extent
      of deformability, and that Tween 20 provided the highest level of deformability.
      Accordingly, we used Tween 20 to formulate deformable liposomes containing
      retinol in the membrane bilayers, and conducted a skin permeation study in Franz
      diffusion cells, using dermatomed human skin and three-dimensional human
      keratinocyte layers. As compared with the use of conventional neutral or
      negatively-charged liposomes, the use of Tween 20-based deformable liposomes
      significantly increased the skin permeation of retinol. These results suggested
      that deformable liposomes might be of potential use for the formulation of
      retinol and other lipophilic functional cosmetic compounds.

PMID- 16451744
TI  - Design, synthesis and characterization of captopril prodrugs for enhanced
      percutaneous absorption.
AB  - Most drugs are designed primarily for oral administration, but the activity and
      stability profiles desirable for this route often make them unsuitable for
      transdermal delivery. We were therefore interested in designing analogues of
      captopril, a model drug with poor percutaneous penetration, for which the
      sustained steady-state blood plasma level associated with transdermal delivery
      (and which is unattainable orally) would be particularly beneficial. Quantitative
      structure-permeability relationships (QSPRs) predicted that ester and thiol
      prodrug derivatives of captopril would have lower maximal transdermal flux (J(m))
      than the parent drug, since the increases in permeability coefficient (k(p)) of
      prodrugs would be outweighed by the reductions in aqueous solubility. Therefore,
      the aim of this study was to synthesize a series of prodrugs of captopril and to
      determine if a QSPR model could be used to design therapeutically viable
      prodrugs. Molecules with the highest predicted k(p) values were synthesized and
      characterized, and J(m) measured in Franz diffusion cells from saturated aqueous
      donor across porcine skin (fresh and frozen). In-vitro metabolism was also
      measured. Captopril and the prodrugs crossed the skin relatively freely, with
      J(m) being highest for ethyl to butyl esters. Substantial first-order metabolism
      of the prodrugs was observed, suggesting that their enhanced percutaneous
      absorption was complemented by their metabolic performance. The results suggested
      that QSPR models provided excellent enhancements in drug delivery. This was not
      seen at higher lipophilicities, suggesting that issues of solubility need to be
      considered in conjunction with any such use of a QSPR model.

PMID- 16451745
TI  - Characterization of pilocarpine-loaded chitosan/Carbopol nanoparticles.
AB  - Patients using ophthalmic drops are faced with frequent dosing schedules and
      difficult drop instillation. Therefore, a long-lasting pilocarpine-loaded
      chitosan (CS)/Carbopol nanoparticle ophthalmic formulation was developed. The
      physicochemical properties of the prepared nanoparticles were investigated using
      dynamic light scattering, zeta-potential, transmission electron microscopy,
      Fourier transform infrared ray spectroscopy (FT-IR) and differential scanning
      calorimetry (DSC). The sustained-release effects of pilocarpine-loaded
      nanoparticles were evaluated using in-vitro release and in-vivo miotic tests, and
      compared with pilocarpine in solution, gel and liposomes. We found that the
      prepared nanoparticles were about 294 nm in size. DSC and FT-IR studies suggested
      that an electrostatic interaction between CS and Carbopol contributes at least in
      part to the stabilization of pilocarpine/CS/Carbopol nanoparticles. When compared
      with pilocarpine in solution, gel or liposomes, the best slow-release profile of
      pilocarpine from the prepared nanoparticles occurred in a dissolution test. In
      the in-vivo miotic study, pilocarpine-loaded CS/Carbopol nanoparticles showed the
      most significant long-lasting decrease in the pupil diameter of rabbits. The
      advantages of CS and Carbopol are good biocompatibility, biodegradability and low
      toxicity. CS is also a mucoadhesive polymer. Thus, pilocarpine/CS/Carbopol
      nanoparticles may provide an excellent potential alternative ophthalmic sustained
      release formulation of pilocarpine for clinical use. CS/Carbopol nanoparticles
      may also be useful for a variety of other therapeutic delivery systems.

PMID- 16451746
TI  - Amphiphilogels as drug carriers: effects of drug incorporation on the gel and on
      the active drug.
AB  - Amphiphilogels (a subset of organogels) are being studied as drug carriers in our
      laboratories. In this paper, the effects of drug incorporation on the drugs and
      the gels are discussed. Amphiphilogels were prepared by heating a mixture of the
      gelator (sorbitan monostearate or sorbitan monopalmitate) and the liquid (e.g.
      Tweens or liquid Spans) to form a solution/dispersion, which was cooled to the
      gel state. Drugs were dissolved by heating a mixture of the drug and the gel and
      cooling the resulting solution. Hydrophilic gels (composed of hydrophilic Tweens
      as the liquid) were more effective solvents than hydrophobic ones (composed of
      hydrophobic Span 20 or 80 liquids). The latter's solvent capacity could, however,
      be increased by the inclusion of co-solvents, such as propylene glycol and
      ethanol. Drug incorporation at 10% w/w did not cause any detrimental changes in
      gel stability, while the drug's release rate was dependent on its concentration
      and on the nature of the gel's liquid component (which influences drug
      solubility), but not on gelator concentration or on the method of drug
      incorporation. This study shows the importance of the nature of the gels' liquid
      component and the possibility of using hydrophilic amphiphilogels as solvents for
      poorly water-soluble drugs.

PMID- 16451747
TI  - Activation of P2Y receptor enhances high-molecular compound absorption from rat
      ileum.
AB  - While there are no reports concerning the effects of extracellular nucleotides on
      the intestinal absorption of drugs, it is well known that extracellular
      nucleotides are important regulators of intestinal epithelial ion transport. This
      report using fluorescein isothiocyanate dextran 4000 (FD-4) as the model compound
      is the first to investigate the effects of purine nucleotides on absorption of
      poorly absorbed drugs from intestine. ATP enhanced the absorption of FD-4 from
      rat ileum in a concentration-dependent manner. ADP also enhanced the absorption
      of FD-4. Other purine nucleotides (adenosine, AMP, UTP and UDP) did not show an
      absorption-enhancing effect. The absorption-enhancing effect by ATP was inhibited
      by suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS), which
      are known P2 receptor antagonists. Additionally, 2-methylthio ATP (a P2Y receptor
      agonist) enhanced the absorption of FD-4, but alpha,beta-methylene ATP (a P2X
      receptor agonist) did not. These findings suggest that activation of the P2Y
      receptor may improve the absorption of water-soluble and high-molecular compounds
      from the ileum.

PMID- 16451748
TI  - Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet
      long-term in mice.
AB  - Three low molecular weight chitosans (molecular weight: 21, 46 and 130 kDa)
      obtained by enzymatic hydrolysis of a high molecular weight chitosan (average
      molecular weight: 650 kDa) had low viscosity and were water-soluble. The effects
      of these water-soluble chitosans on pancreatic lipase (in-vitro) and the
      elevation of plasma triacylglycerol concentration after the oral lipid tolerance
      test were examined in mice. The water-soluble 46-kDa chitosan was the most
      effective at inhibiting pancreatic lipase activity (in-vitro) and plasma
      triacylglycerol elevation after the oral lipid tolerance test. Based on this
      result, the effects of the 46-kDa chitosan on increases in bodyweight, various
      white adipose tissue weights, and plasma and liver lipids were examined in mice
      fed a high-fat diet for 20 weeks. Water-soluble 46-kDa chitosan (300 mg kg(-1),
      twice daily) prevented increases in bodyweight, various white adipose tissue
      weights and liver lipids (cholesterol and triacylglycerol) in mice fed a high-fat
      diet, and further increased the faecal bile acid and fat. The results suggest
      that the lipid-lowering effects of the 46-kDa chitosan may be mediated by
      increases in faecal fat and/or bile acid excretion resulting from the binding of
      bile acids, and by a decrease in the absorption of dietary lipids
      (triacylglycerol and cholesterol) from the small intestine as a result of the
      inhibition of pancreatic lipase activity. Water-soluble 46-kDa chitosan (100 and
      300 mg kg(-1), twice daily) did not cause liver damage with the elevation of
      glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, or kidney
      damage with the elevation of blood nitrogen urea. It was concluded that water
      soluble 46-kDa chitosan is a safe functional food.

PMID- 16451749
TI  - Synthesis and binding profile of constrained analogues of N-[4-(4-arylpiperazin-1
      yl)butyl]-3-methoxybenzamides, a class of potent dopamine D3 receptor ligands.
AB  - We recently reported on a series of N-[4-(4-arylpiperazin-1-yl)butyl]-3
      methoxybenzamides, endowed with high affinity for dopamine D(3) receptors, but
      lacking of selectivity over D(4), D(2), 5-HT(1A), and alpha(1)-receptors. To
      improve the D(3)-receptor affinity and selectivity, without causing a
      considerable increasing in the lipophilicity, the flexible butyl linker was
      replaced by a more conformationally constrained cyclohexyl linker. The new cis-
      and trans-N-[4-(4-aryl-1-piperazinyl)cyclohexyl]-3-methoxybenzamides (Aryl= 2,3
      di-Cl-Ph, 2-CH(3)O-Ph, 4-Cl-Ph, 2,3-di-CH(3)-Ph) were tested in-vitro for their
      binding affinity for D(3), D(4), D(2), 5-HT(1A), and alpha(1)-receptors. The
      trans- derivatives were found to be more potent at D(3) receptor than the
      corresponding cis- isomers, but less potent than the opened counterparts. This
      reflected negatively on the selectivity over the other studied receptors.
      Derivative trans-N-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]cyclohexyl}-3
      methoxybenzamide (trans-7) showed high D(3)-receptor affinity (K(i)=0.18 nM) and
      a relevant selectivity over D(4), D(2), 5-HT(1A), and alpha(1)-receptors (>200
      fold). This compound was characterized as a full agonist at D(3) receptor when
      tested in the Eu-GTP binding assay.

PMID- 16451750
TI  - Evaluation of in-vitro anti-inflammatory activity of some 2-alkyl-4,6-dimethoxy
      1,3,5-triazines.
AB  - The ability of some 2-alkyl(aryl)-4,6-dimethoxy-1,3,5-triazine derivatives to
      interfere with production of reactive oxygen species (ROS) by human phagocytes
      was evaluated in an in-vitro cell model. Superoxide anion (O(2)(-*)) production
      by human polymorphonuclear cells (PMNs), challenged by the chemotactic agent N
      formylmethionyl-leucyl-phenylalanine (FMLP), was inhibited in a dose-dependent
      manner by all the compounds tested, compounds 3, 4 and 5 being statistically the
      most active. Adhesion of PMNs to vascular endothelial cells (ECs) is a critical
      step in recruitment and infiltration of leucocytes into tissues during
      inflammation, and the effects of 1,3,5-triazine derivatives on PMN adhesion to
      ECs from the human umbilical vein (HUVEC) were also investigated. Triazines were
      incubated with PMNs and HUVEC; adhesion was quantitated by computerized micro
      imaging fluorescence analysis. The 1,3,5-triazines tested inhibited the adhesion
      evoked by pro-inflammatory stimuli, such as platelet activating factor (PAF),
      FMLP, phorbol myristate acetate (PMA), tumour necrosis factor-alpha (TNF-alpha)
      and interleukin-1beta(IL-1beta) in a dose-response manner over the concentration
      range 10(-9) to 10(-4)M, compounds 5 and 6 being the most active. Both of these
      compounds inhibited PMN adhesion to HUVEC, even when endothelial or PMN stimuli
      were used. Indeed, when both cell populations were activated contemporarily, the
      anti-adhesive effect was enhanced. The study suggests that 2-aryl-4,6-dimethoxy
      1,3,5-triazines deserve further evaluation as anti-inflammatory agents.

PMID- 16451751
TI  - Mechanism underlying mitochondrial protection of asiatic acid against
      hepatotoxicity in mice.
AB  - Asiatic acid (AA) is one of the triterpenoid components of Terminalia catappa L.,
      which has antioxidative, anti-inflammatory and hepatoprotective activity. This
      research focused on the mitochondrial protection of AA against acute liver injury
      induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) in mice. It was
      found that pretreatment with 25, 50 or 100 mg kg(-1) AA significantly blocked the
      LPS + D-GalN-induced increase in both serum aspartate aminotransferase (sAST) and
      serum alanine aminotransferase (sALT) levels, which was confirmed by
      ultrastructural observation under an electron microscope, showing improved
      nuclear condensation, ameliorated mitochondrion proliferation and less lipid
      deposition. Meanwhile, different doses of AA could decrease both the
      transcription and the translation level of voltage-dependent anion channels
      (VDACs), the most important mitochondrial PTP component protein, and block the
      translocation of cytochrome c from mitochondria to cytosol. On the other hand,
      pre-incubation with 25, 50 and 100 microg mL(-1) AA inhibited the Ca(2+)-induced
      mitochondrial permeability transition (MPT), including mitochondrial swelling,
      membrane potential dissipation and releasing of matrix Ca(2+) in liver
      mitochondria separated from normal mice, indicating the direct role of AA on
      mitochondria. Collectively, the above data suggest that AA could protect liver
      from damage and the mechanism might be related to up-regulating mitochondrial
      VDACs and inhibiting the process of MPT.

PMID- 16451752
TI  - In-vitro and in-vivo antitumour activity of physalins B and D from Physalis
      angulata.
AB  - We have evaluated the in-vitro and in-vivo antitumour activity of physalin B and
      physalin D isolated from the aerial parts of Physalis angulata. In-vitro, both
      compounds displayed considerable cytotoxicity against several cancer cell lines,
      showing IC50 values in the range of 0.58 to 15.18 microg mL(-1) for physalin B,
      and 0.28 to 2.43 microg mL(-1) for physalin D. The antitumour activity of both
      compounds was confirmed in-vivo using mice bearing sarcoma 180 tumour cells. The
      in-vivo antitumour activity was related to the inhibition of tumour
      proliferation, as observed by the reduction of Ki67 staining in tumours of
      treated animals. Histopathological examination of the kidney and liver showed
      that both organs were affected by physalin treatment, but in a reversible manner.
      These compounds were probably responsible for the previously described antitumour
      activity of ethanol extracts of P. angulata, and their identification and
      characterization presented here could explain the ethnopharmacological use of
      this species in the treatment of cancer.

PMID- 16451754
TI  - In-vitro effect of flavonoids from Solidago canadensis extract on glutathione S
      transferase.
AB  - Solidago canadensis is typical of a flavonoid-rich herb and the effect of an
      aqueous ethanol extract on glutathione-S-transferase (GST) activity using HepG2
      cells was compared with those of the flavonol quercetin and its glycosides
      quercitrin and rutin, found as major constituents. The composition of the extract
      was determined by HPLC and rutin was found to be the major flavonoidal component
      of the extract. Total GST activity was assessed using 1-chloro-2,4-dinitrobenzene
      as a substrate. The glycosides rutin and quercitrin gave dose-dependent increases
      in GST activity, with a 50% and 24.5% increase at 250 mM, respectively, while the
      aglycone quercetin inhibited the enzyme by 30% at 250 mM. The total extract of
      the herb gave an overall dose-dependent increase, the fractions corresponding to
      the flavonoids showed activating effects while those containing caffeic acid
      derivatives were inhibitory. The activity observed corresponds to that reported
      for similar compounds in-vivo using rats, thus the HepG2 cell line could serve as
      a more satisfactory method of assessing the effects of extracts and compounds on
      GST.

PMID- 16451753
TI  - Effects of Ginkgo biloba extract on blood pressure and vascular endothelial
      response by acetylcholine in spontaneously hypertensive rats.
AB  - We previously demonstrated that Ginkgo biloba extract (Ginkgo) produced
      vasodilation via the nitric oxide pathway in aortic segments isolated from Wistar
      rats. In this study, we have analysed the effects of daily long-term oral Ginkgo
      treatment on blood pressure, vascular tone, and calcium mobilization to evaluate
      the clinical availability. Spontaneously hypertensive rats (SHR) and Wistar Kyoto
      rats (WKY) were fed either a control diet or a diet containing 0.05%-0.5% Ginkgo
      for 30 days. Administration of Ginkgo did not change systolic blood pressure in
      WKY, but significantly decreased systolic blood pressure in SHR. In thoracic
      aortic preparations isolated from SHR, diminished relaxation in response to
      acetylcholine was improved by a Ginkgo-containing diet. This diet significantly
      decreased the EC50 value and significantly increased maximum relaxation in
      response to acetylcholine in SHR. In aortic segments isolated from WKY,
      acetylcholine-induced relaxation was not affected by a Ginkgo-containing diet.
      Sodium nitroprusside-induced relaxation was unchanged by a Ginkgo-containing diet
      in SHR and WKY. We also examined the effects of a Ginkgo-containing diet on the
      intracellular calcium level of aortic endothelium using a fluorescent confocal
      microscopic imaging system. Calcium Green 1/AM preloading indicated that
      acetylcholine significantly increased the endothelial intracellular calcium
      level. The Ginkgo-containing diet significantly enhanced this increase in the
      aortic endothelium of SHR, but did not change that of WKY. The results suggested
      that Ginkgo enhanced endothelium-dependent vasodilation and elevation of the
      endothelial intracellular Ca(2+) level in SHR, resulting in hypotension. This
      accelerative effect of Ginkgo on Ca(2+) mobilization seemed to be associated with
      restoration of impaired dilatory function induced by acetylcholine in endothelial
      cells.

PMID- 16451755
TI  - Protective effect of Nardostachys jatamansi on oxidative injury and cellular
      abnormalities during doxorubicin-induced cardiac damage in rats.
AB  - Nardostachys jatamansi is a medicinally important herb of Indian origin. It has
      been used for centuries in the Ayurvedic and Unani systems of medicine for the
      treatment of various ailments. We have evaluated the effect of N. jatamansi
      (rhizomes) on the biochemical changes, tissue peroxidative damage and abnormal
      antioxidant levels in doxorubicin (adriamycin)-induced cardiac damage.
      Preliminary studies on the effect of the graded dose of extract showed that 500
      mg kg(-1) orally for seven days was found to be optimum and hence all further
      study was carried out with this particular dose. Rats administered doxorubicin
      (15 mg kg(-1), i.p.) showed myocardial damage that was manifested by the
      elevation of serum marker enzymes (lactate dehydrogenase, creatine phosphokinase,
      aspartate aminotransaminase and alanine aminotransaminase). The animals showed
      significant changes in the antioxidant enzymes (superoxide dismutase, catalase,
      glutathione peroxidase and glutathione-S-transferase) and lipid peroxidation
      levels. Pretreatment with N. jatamansi extract significantly prevented these
      alterations and restored the enzyme activity and lipid peroxides to near normal
      levels. Restoration of cellular normality accredits the N. jatamansi with a
      cytoprotective role in doxorubicin-induced cardiac damage.

PMID- 16451756
TI  - Effect of berberine on proliferation, biosynthesis of macromolecules, cell cycle
      and induction of intercalation with DNA, dsDNA damage and apoptosis in Ehrlich
      ascites carcinoma cells.
AB  - Our primary aim was to study berberine, a potential anti-cancer drug, for its
      cytotoxic and antiproliferative activity in-vitro using Ehrlich ascites carcinoma
      (EAC) cells. Cytotoxicity was measured by the growth inhibition assay. We
      investigated the effect of berberine on the biosynthesis of macro-molecules (DNA,
      RNA, proteins), cell cycle effects and induction of dsDNA damage and apoptosis in
      berberine-treated EAC cells. Our results showed that berberine acts cytotoxically
      on EAC cells. The cytotoxicity was directly concentration and time dependent. The
      highest cytotoxic concentrations (100 and 50 microg mL(-1)) induced intercalation
      of berberine with DNA, formation of dsDNA breaks, inhibition of DNA synthesis and
      death of EAC cells. A concentration of 10 mug mL(-1) induced clear apoptotic cell
      death, which was followed by inhibition of protein synthesis.

PMID- 16451757
TI  - Paracellular and transcellular pathways facilitate insulin permeability in rat
      gut.
AB  - The aim of this study was to conduct a systematic investigation of the absorption
      of insulin in the rat intestine in the presence of permeation enhancers and
      protease inhibitors. An in-situ perfused rat gut model was used for the co
      perfusion of insulin and PEG 4000 in the presence or absence of bile salts, bile
      salt:fatty acid surfactant systems and protease inhibitors. Perfusion experiments
      were conducted for 180 min with perfusate and blood collection at regular
      intervals. Permeability coefficients for insulin were calculated from plasma
      insulin and PEG 4000 permeability coefficients were calculated from lumenal
      disappearance data. In the absence of enzyme inhibitors, insulin permeability was
      consistently lower than PEG 4000, but increased in proportion to PEG 4000
      permeability. Large increases in insulin permeability were obtained for mixed
      micellar systems and protease inhibitors. In the presence of protease inhibitors
      and simple micelle systems, PEG 4000 permeability was three-fold greater than
      insulin permeability. In the presence of absorption enhancers, PEG 4000
      permeability increased up to a maximum value of 3.63 x 10(-6)cm s(-1), a value
      five-fold less than that of the estimated aqueous boundary layer permeability for
      PEG 4000. This suggests that PEG 4000 permeability is primarily membrane
      controlled. Insulin permeability is enhanced to a maximum value of 9.17 x 10(
      6)cm s(-1), suggesting that paracellular transport routes do not account
      exclusively for insulin permeation across the intestinal epithelium. The results
      add support to suggestions that routes other than the paracellular route may
      contribute to insulin absorption in rat gut.

PMID- 16451758
TI  - Protective effects of Swertia longifolia Boiss. and its active compound,
      swerchirin, on paracetamol-induced hepatotoxicity in mice.
AB  - Aerial parts of Swertia longifolia Boiss. (Gentianaceae), which grows in the
      north of Iran, were screened for hepatoprotective activity against paracetamol
      (acetaminophen)-induced hepatotoxicity in Swiss mice. Pretreatment with total
      plant extract and swerchirin, the major component of the plant, significantly
      reduced the elevation of biochemical parameters, AST (aspartate
      aminotransferase), ALT (alanine aminotransferase) and ALP (alkaline phosphatase),
      the enzymes that are increased by liver damage (P < 0.001). Our results indicated
      that total plant extract and swerchirin were hepatoprotective in the range of 6
      50 mg kg(-1) orally.

PMID- 16451762
TI  - Comparison of muscle activity associated with structural differences in dental
      hygiene mirrors.
AB  - PURPOSE: Ergonomic studies suggest that the commonly used pinch grasp, held in a
      static position, is a contributing factor for dental Hygienists' development of
      work-related musculoskeletal disorders (WMSDs) such as carpal tunnel syndrome
      (CTS), Trigger Thumb, de Quervain's stenosing tenosynovitis, and carpometacarpal
      (CMC) osteoarthritis. The pinch grasp is commonly used by the dental hygienist
      while holding the dental mirror in the non-dominant hand. In response to this
      concern, manufacturers are redesigning dental mirror handles. The value of these
      re-designed products is based solely on anecdotal evidence. To date, minimal
      research has been done to examine the non-dominant mirror hand. The purpose of
      this study was to objectively evaluate dental mirror handle design using surface
      electromyography (sEMG) to compare muscle activity associated with grasping the
      mirror. METHODS: This randomized controlled clinical trial utilized a two-by-two
      repeated measures statistical design. Data was collected on a convenience sample
      of 19 (N=19) healthy dental hygiene students in their last year of study. Data
      collection was divided into two phases to maintain a balanced study. The
      independent variables in phase I were diameter and weight. The independent
      variables in phase II were weight and padding. Muscle activity was measured while
      grasping various dental hygiene mirrors in 30-second increments using sEMG.
      Following data collection subjects designated which mirror felt most and least
      comfortable to compare subjective data with objective data. RESULTS: Three
      statistically significant results occurred. In phase II, padding (p=.01)
      demonstrated the largest reduction of muscle activity in the flexor pollicis
      brevis, by decreasing mean muscle activity by 3.7 microv. The interaction of
      diameter and weight (p=.01) in phase I reduced the mean muscle activity in the
      extensor digitorum by .8 microV and weight (p=.02) in phase II decreased the
      muscle activity in the extensor digitorum by .62 microV. Self-reports of comfort
      reported by the subjects in this study were not consistent with the measurements
      of muscle activity using sEMG. CONCLUSION: Ergonomic adaptations to dental
      hygiene mirror handles were associated with increases and decreases in muscle
      activity. The clinical impact of this is amplified as force is exerted.
      Furthermore, it may be possible to reduce WMSDs for dental hygienists by using
      instrument designs during the workday. Self-reports of comfort by the subjects in
      this study did not calibrate with the measurements of muscle activity using sEMG.
      Additional research is needed to further isolate the external variables of the
      study and to determine what actual reduction in muscle activity is significant
      for maintaining musculoskeletal health.

PMID- 16451763
TI  - Ethics instruction in the dental hygiene curriculum.
AB  - PURPOSE: Dental hygiene ethics is an essential component of the dental hygiene
      curriculum. The accreditation standards for dental hygiene education state that
      graduates must be competent in applying ethical concepts to the provision and/or
      support of oral health care services. Although the standards for entry into the
      profession of dental hygiene emphasize the importance of ethical reasoning, there
      is little published research specific to ethics instruction in dental hygiene
      programs. The purpose of this study was to assess how ethics is taught in the
      dental hygiene curriculum. METHODS: A 17-item survey was designed and distributed
      to 261 accredited dental hygiene programs in the United States for a response
      rate of 56% (N=147). The survey requested that participants provide information
      on teaching and evaluation methodologies, didactic and clinical hours of
      instruction, individuals responsible for providing instruction, and the degree of
      emphasis placed on ethics and integration of ethical reasoning within the dental
      hygiene curriculum. RESULTS: Results of the survey reflect that dental hygiene
      programs devote a mean of 20. hours to teaching dental hygiene ethics in the
      didactic component of the curriculum. With regard to the clinical component of
      the curriculum, 63% of respondents indicated that 10 or less hours are devoted to
      ethics instruction. These results show an increase in didactic hours of
      instruction from previous studies where the mean hours of instruction ranged from
      7 to 11.7 hours. Results showed 64% of respondents offered a separate course in
      ethics; however, 82% of programs surveyed indicated that ethics was incorporated
      into one or more dental hygiene courses with 98% utilizing dental hygiene faculty
      to provide instruction. Most programs utilized a variety of instructional methods
      to teach ethics with the majority employing class discussion and lecture (99% and
      97% respectively). The type of institution-technical college, community college,
      four-year university with a dental school, and four-year university without a
      dental school-had little influence on the degree of emphasis placed on teaching
      ethics. Although the number of hours devoted to ethics instruction has increased,
      43% of respondents indicated that they would like to see more emphasis placed on
      ethics in the program with which they are affiliated. CONCLUSION: This study
      reveals that programs have taken measures to employ a variety of teaching
      strategies to ensure that students are competent in applying ethical concepts in
      the provision of oral health care. However, programs continue to rely primarily
      on traditional methods of instruction and evaluation such as lecture, discussion,
      quizzes, and written assignments. Inferential analysis focusing on the influence
      of the type of institution, showed that in general, the type of institution has
      little influence on the level of emphasis placed on teaching ethics in dental
      hygiene curricula. It is recommended that dental hygiene programs continue to
      implement and evaluate instructional methods that simulate real life experiences
      and emphasize ethical concepts that promote comprehensive oral health care.
      Future studies should investigate the effectiveness of ethics instruction within
      dental hygiene curricula.

PMID- 16451764
TI  - Differences between herbal and nonherbal users in dental practice.
AB  - PURPOSE: The purposes of this study were to describe basic demographics and
      health belief differences between herb users and nonherb users, any potential
      herb-drug interactions, and examine the association between dental chart noted
      and questionnaire self-reported use of herbal remedies. METHODS: A 3-part survey
      instrument was administered to a convenience sample of 149 individuals at a
      dental clinic and two dental practices. The first part ascertained demographic
      information and prescription drug use using open-ended and closed-ended
      questions. The second part listed 51 individual/combination herbs and the third
      part assessed healthcare behavior using a 5-point Likert scale. A chart audit
      compared written responses between a patient's medical/dental history chart and
      his/her survey on herbal use. Descriptive analyses and MANOVA were used to
      examine the relationship between herbal users and nonusers. RESULTS: Eighty
      participants (54%) reported using some form of herbs. They were characterized as
      mostly female (71%), who were less likely to disclose herbal usage to
      practitioners (p< .05), believed in herbal effectiveness (p< .05), and reported a
      more positive perceived level of health status compared to nonusers (p= .02).
      Although herb users reported a willingness to disclose use of herbs to health
      practitioners, only three patients had any written documentation of their herb
      use in their medical/dental health chart (p= .0001). Fifty-five herb users were
      also taking prescription drugs (69%) that could potentially lead to herb-drug
      interactions. CONCLUSION: The findings provide supportive evidence that dental
      hygiene practitioners need to be aware of their patients' use of herbs. Knowing
      potential risks, side effects, and possible drug interactions is necessary for
      patient management and each patient's oral health.

PMID- 16451765
TI  - Sulcular sulfide monitoring: an indicator of early dental plaque-induced gingival
      disease.
AB  - PURPOSE: The purpose of this study was to evaluate the relationship between
      volatile sulfur compounds (VSC) and gingival health status and to determine if
      volatile sulfur compounds can detect early dental plaque-induced gingival
      disease. METHODS: A split-mouth design with randomly selected quadrants of the
      mandibular arch enabled 39 participants to serve as their own controls. At
      baseline and at three subsequent appointments (days 7, 14, and 21) gingival
      inflammation (GI), bleeding on probing (BOP), and sulfide levels (SUL) were
      measured using the Gingival Index and the Diamond Probe/Perio 2000 System. For
      three weeks, participants refrained from brushing and flossing one randomly
      selected quadrant of the mandibular arch. The Pearson correlation test was used
      to determine the relationship between sulfide concentrations and gingival health.
      The Wilcoxon signed rank test was used to compare the differences in mean GI,
      BOP, and SUL scores between the hygiene side (H) and the non-hygiene side (NH).
      RESULTS: Data suggest that SUL correlate positively to GI and BOP on both sides;
      however, the strength of the correlation was stronger for the NH side. A
      comparison of mean GI, BOP, and SUL scores revealed a statistically significant
      difference between sides for all three parameters from baseline to day 21, except
      for SUL on day 14. CONCLUSIONS: Based on study outcomes, the Diamond Probe/Perio
      2000 System demonstrated the ability to detect sites with elevated SUL;
      therefore, SUL may be a useful adjunctive indicator of early plaque-induced
      gingivitis. In addition, data revealed a moderate correlation between SUL levels
      and gingival inflammation on the NH sides. Whether sulfur by-product is a
      contributor to the disease process, or merely a correlate, is inconclusive.

PMID- 16451766
TI  - The comparative effects of 0.12% chlorhexidine and herbal oral rinse on dental
      plaque-induced gingivitis.
AB  - PURPOSE: The purpose of this study was to determine the effects of two oral
      rinses-one 0.12% chlorhexidine rinse (CHX) and one herbal rinse (HBR)-on gingival
      health status over time. METHODS: Sixty-three participants were randomly assigned
      to one of three treatment groups: CHX, HBR, or placebo. For three months,
      participants rinsed twice daily (morning and evening) with (1/2) ounce of
      allocated rinse after brushing and flossing. Individuals were given the same type
      of soft bristle toothbrush and whitening toothpaste. No attempt was made to
      modify participants' routine oral care, except they were advised to refrain from
      use of any other oral rinse for the duration of the study. Data were collected at
      baseline (B), month one (1), two (2), and three (3) utilizing the Gingival Index
      (GI), Plaque Index (PI), and bleeding on probing (BOP). A full mouth periodontal
      probing was performed at baseline and at the completion of the study. A soft
      tissue oral assessment was completed at each visit. CHX, HBR, and placebo data
      were compared between three time intervals, B-1, B-2, and B-3. Statistical
      analysis was conducted by means of multiple regression using generalized linear
      models. Paired comparison tests--ANOVA followed by a post hoc Tukey test--were
      used to confirm results. RESULTS: CHX was the only oral rinse to demonstrate a
      statistically significant effect on the reduction of mean GI, BOP, and PI scores
      when compared to placebo. CHX demonstrated a 31% reduction in the proportion of
      GI scores between B-2 and a 29% reduction between B-3 (p=.003 and p=.012,
      respectively). CHX demonstrated a 19% reduction of BOP sites between B-1, 32%
      reduction between B-2, and 29% reduction between B-3 (p=.028, p=.000, and p=.005,
      respectively). CHX demonstrated a 20% reduction in PI scores between B-1, and a
      28% reduction between B-2 (p=.005 and p=.032, respectively). The effects of HBR
      on reducing mean GI, BOP, and PI scores were not statistically greater than
      placebo at any time during the study.

PMID- 16451768
TI  - Coverage policy and use beyond the FDA-approved label.

PMID- 16451770
TI  - Indication and timing of thyroid surgery for patients with hereditary medullary
      thyroid cancer syndromes.
AB  - Hereditary medullary thyroid cancer syndromes comprise familial medullary thyroid
      cancer (FMTC) and multiple endocrine neoplasia types 2A and 2B. Hereditary
      medullary thyroid cancers have an autosomal dominant pattern of inheritance and
      are caused by activating germline point mutations in the RET proto-oncogene.
      Evaluation of the onset, extent, and progression of hereditary medullary thyroid
      cancer associated with specific RET mutations has enabled clinicians to treat
      patients based on the level of risk associated with their specific mutation.
      Children identified by RET screening to be at risk for the development of
      medullary thyroid cancer can be treated with prophylactic thyroidectomy before
      developing the disease. This review covers the diagnosis, evaluation, timing of
      surgical management, and optimal follow-up of patients with hereditary medullary
      thyroid cancer syndromes.

PMID- 16451769
TI  - Neuroendocrine tumors.

PMID- 16451771
TI  - Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1.
AB  - The surgical management of pancreatic endocrine tumors in patients with multiple
      endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are
      the 2 most common functional pancreatic neuroendocrine tumors in patients with
      multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid
      hypersecretion and peptic ulcer disease that are best managed using proton pump
      inhibitors. Surgery to remove the gastrinoma in patients with multiple endocrine
      neoplasia type 1 is seldom curative unless a more extensive Whipple
      pancreaticoduodenectomy is performed. Because the prognosis is excellent,
      aggressive resections such as a Whipple procedure are only indicated for large,
      locally metastatic, advanced tumors. Furthermore, surgery to remove imageable
      tumors that are 2 cm in diameter is associated with excellent outcomes and
      decreased probability of liver metastases. Because gastrinomas are commonly
      multiple and most originate in the duodenum and develop lymph node metastases,
      the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas
      cause hypoglycemia that results in neuroglycopenic symptoms. Medical management
      of the hypoglycemia is less effective than that of the gastric acid
      hypersecretion. Fortunately, the insulinoma is usually clearly identified using
      routine pancreatic imaging studies. There is a high likelihood of cure when the
      insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and
      careful follow-up is indicated.

PMID- 16451772
TI  - Genetic/familial high-risk assessment: breast and ovarian.

PMID- 16451773
TI  - Bilateral risk-reducing oophorectomy in BRCA1 and BRCA2 mutation carriers.
AB  - Bilateral risk-reducing oophorectomy (BRRO) is widely used for cancer risk
      reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations. BRRO significantly
      reduces breast cancer risk by approximately 50% and ovarian cancer risk by 85% to
      95%, but it may be accompanied by menopausal symptoms, impaired quality of life,
      and accelerated bone loss. Therefore, decisions regarding the timing of BRRO, the
      risks and benefits of a simultaneous hysterectomy, and the use of hormone
      replacement therapy (HRT) must be made in concert with the patient and
      individualized to their circumstances. However, recent data demonstrate that HRT
      after BRRO in unaffected premenopausal women does not negate the breast cancer
      risk reduction that BRRO provides. This article reviews the studies regarding
      BRRO in BRCA1/2 mutation carriers, with particular focus on the use of HRT.

PMID- 16451775
TI  - Extended-regimen contraception: effects on menstrual symptoms and quality of
      life.

PMID- 16451774
TI  - Ethical obligations and counseling challenges in cancer genetics.
AB  - Cancer genetics is creating new practice opportunities in medical genetics,
      oncology, and primary care. The ethical and counseling challenges of this new
      area of practice are not unique but sometimes take new form in the context of
      genetic risk. This article uses cases to explore the issues associated with
      shared family risk, including competing concerns of family members, duty to warn
      relatives of genetic risk, and testing of children and other relatives. The
      ethical obligations of clinicians start with the need to maintain competence in
      the face of rapidly evolving science. Clinicians should be able to identify
      patients within their practice who are candidates for genetic testing. When
      genetic susceptibility to cancer is identified, patients should be offered
      counseling and follow-up, with referral as appropriate, to ensure delivery of
      care consistent with current standards. When patients experience barriers to
      needed health care, clinicians should advocate for their needs. Clinicians must
      ensure the autonomy and informed decision-making of all members of cancer-prone
      families. Clinicians must also provide emotional support and accurate information
      about cancer risks and cancer risk reduction measures, including uncertainties.
      Teamwork among different specialties is important in addressing these challenges.

PMID- 16451776
TI  - Cephalosporins can be prescribed safely for penicillin-allergic patients.
AB  - The widely quoted cross-allergy risk of 10% between penicillin and cephalosporins
      is a myth. Cephalothin, cephalexin, cefadroxil, and cefazolin confer an increased
      risk of allergic reaction among patients with penicillin allergy. Cefprozil,
      cefuroxime, cefpodoxime, ceftazidime, and ceftriaxone do not increase risk of an
      allergic reaction.

PMID- 16451777
TI  - Disaster medical response: maximizing your effectiveness.
AB  - In the aftermath of Hurricane Katrina, physicians and other health professionals
      volunteered for deployment to the affected area to provide medical services. The
      frustrating reality most of them encountered was the incapacity of those in
      charge to use the number of professional volunteers expressing interest.
      Untrained volunteers, though well intentioned, are often not that helpful. The
      immediate needs of a disaster area relate to public health and other safety
      issues. Until a proper infrastructure is re-established, general medical services
      cannot be provided. Physician services are most effectively provided in
      collaboration with, or as part of, an organized local response agency.

PMID- 16451778
TI  - Chest pain, weakness, and elevated cardiac enzymes: how would you treat?
AB  - You are making rounds in the hospital one Saturday morning when you receive a
      call from the emergency department saying a 68-year-old man is having chest pain,
      weakness, and "positive cardiac enzymes." His electrocardiogram (ECG) reading is
      reported as unremarkable. Because it is the weekend and no cardiology
      consultation is available at your hospital, the family medicine resident wants to
      know if you would like to admit the patient to your service or transfer him to a
      larger hospital. You decide that you can best make this decision by going to the
      emergency department and personally evaluating the patient.

PMID- 16451779
TI  - Annular rash on a newborn.
AB  - A full-term, healthy female newborn was delivered via cesarean section because
      the labor did not adequately progress. The mother, age 33 years and of Asian
      ancestry, had a significant medical and obstetrical history: chronic hepatitis B
      carrier without cirrhosis, cutaneous lupus erythematosus (positive anti-Ro and
      anti-La antibodies), and a positive group B streptococcal recto-vaginal culture
      at 35 weeks' gestation. The mother received 4 doses of intravenous ampicillin
      during labor. The infant's initial hospital course was complicated by a transient
      and otherwise asymptomatic bradycardia. An electrocardiogram (ECG) confirmed a
      heart rate of 96 with normal interval parameters, but there were changes
      suggestive of left ventricular hypertrophy. An echocardiogram was normal. Follow
      up office visits for common newborn feeding problems demonstrated consistent
      weight gain and normal vital signs, including heart rate and facial milia.
      However, by age 4 weeks an erythematous eruption extending from the frontal scalp
      and forehead to the cheek area had developed. What is the differential diagnosis?
      What tests should be done to make the diagnosis?

PMID- 16451780
TI  - Is pulse palpation helpful in detecting atrial fibrillation? A systematic review.
AB  - BACKGROUND: Atrial fibrillation in the elderly is common and potentially life
      threatening. The classical sign of atrial fibrillation is an irregularly
      irregular pulse. OBJECTIVE: The objective of this research was to determine the
      accuracy of pulse palpation to detect atrial fibrillation. METHODS: We searched
      Medline, EMBASE, and the reference lists of review articles for studies that
      compared pulse palpation with the electrocardiogram (ECG) diagnosis of atrial
      fibrillation. Two reviewers independently assessed the search results to
      determine the eligibility of studies, extracted data, and assessed the quality of
      the studies. RESULTS: We identified 3 studies (2385 patients) that compared pulse
      palpation with ECG. The estimated sensitivity of pulse palpation ranged from 91%
      to 100%, while specificity ranged from 70% to 77%. Pooled sensitivity was 94%
      (95% confidence interval [CI], 84%-97%) and pooled specificity was 72% (95% CI,
      69%-75%). The pooled positive likelihood ratio was 3.39, while the pooled
      negative likelihood ratio was 0.10. CONCLUSIONS: Pulse palpation has a high
      sensitivity but relatively low specificity for atrial fibrillation. It is
      therefore useful for ruling out atrial fibrillation. It may also be a useful
      screen to apply opportunistically for previously undetected atrial fibrillation.
      Assuming a prevalence of 3% for undetected atrial fibrillation in patients older
      than 65 years, and given the test's sensitivity and specificity, opportunistic
      pulse palpation in this age group would detect an irregular pulse in 30% of
      screened patients, requiring further testing with ECG. Among screened patients,
      0.2% would have atrial fibrillation undetected with pulse palpation.

PMID- 16451781
TI  - The liver transplant recipient: what you need to know for long-term care.
AB  - In general, long-term treatment of hypertension, diabetes, and obesity after
      liver transplantation is similar to that for the general population. Measure bone
      density within the first year after transplantation. Treat osteoporosis with
      standard agents. Joint replacement surgery appears safe in this group of
      patients. Resume standard screening for malignancy 2 to 3 years after
      transplantation, and repeat at intervals similar to that used with the general
      population. Given the high risk of skin cancer, transplant recipients should wear
      sunblock (SPF >40) and have routine dermatologic examinations. Patients should
      wait at least 2 years before considering pregnancy and use barrier-type methods
      in this period. Vaccinate patients against hepatitis A and B, influenza, and
      pneumococcus. Avoid live vaccines.

PMID- 16451782
TI  - What is the appropriate management for a patient with CIN1 on colposcopy?
AB  - Of the different strategies available for managing cervical intraepithelial
      neoplasia grade 1 (CIN1), testing for high-risk subtypes of the human
      papillomavirus (hr-HPV) DNA at 12 months has the highest sensitivity for
      predicting the development of CIN2 or CIN3 and leads to the lowest rate of
      referral to repeat colposcopy. If the hr-HPV DNA test result is negative at 12
      months, then the patient may return to routine cytology screening. If the hr-HPV
      DNA test result is positive, the patient should undergo repeat colposcopy.

PMID- 16451783
TI  - How safe is vaginal birth after cesarean section for the mother and fetus?
AB  - Compared with planned repeat low-transverse cesarean section, vaginal birth after
      cesarean section (VBAC) is not associated with increased risk of maternal or
      neonatal mortality (strength of recommendation [SOR]: B). Morbidity is slightly
      increased, as evidenced by higher uterine rupture rates and some neonatal outcome
      measures (SOR: B).

PMID- 16451784
TI  - What is the best surveillance for hepatocellular carcinoma in chronic carriers of
      hepatitis B?
AB  - Screening patients with chronic hepatitis B infection (HBsAg+) for hepatocellular
      carcinoma by alpha-fetoprotein (AFP) or by AFP plus ultrasound (AFP/US) detects
      hepatocellular carcinoma tumors at earlier stages and increases resection rates
      (strength of recommendation [SOR]: B, based on a systematic review of fair
      quality randomized controlled trials). It is unclear whether screening with AFP
      or AFP/US improves disease-specific or all-cause mortality (SOR: B).

PMID- 16451786
TI  - What is the recommended approach to asymptomatic patients who develop a reactive
      PPD?
AB  - Clinical evaluation and chest x-ray are recommended for asymptomatic patients
      with a positive purified protein derivative (PPD) test result, to exclude the
      slight possibility of active tuberculosis (TB). Patients with radiographic
      evidence of old (healed) TB infection should also undergo sputum testing
      (strength of recommendation [SOR]: C, expert opinion). Treatment with isoniazid
      (INH) monotherapy (300 mg/d) reduces progression of latent tuberculosis to active
      disease (SOR: A, large randomized controlled trials [RCT]), with 9 months as the
      optimal treatment length (SOR: B, derivation from RCTs). A 3-month course of
      combined rifampin (600 mg/d) and INH (300 mg/d) is equivalent in efficacy to INH
      monotherapy and is associated with similar rates of toxicity (SOR: A, meta
      analysis of RCTs), but this regimen is not included in Centers for Disease
      Control and Prevention recommendations.

PMID- 16451785
TI  - Are major bleeding events from falls more likely in patients on warfarin?
AB  - There is no evidence of increased risk for major bleeding as a result of falls in
      hospitalized patients taking warfarin (strength of recommendation [SOR]: B, based
      on retrospective cohort studies). In the average patient taking warfarin for
      atrial fibrillation, the risk of intracranial hemorrhage from a fall is much
      smaller than the benefit gained from reducing risk of stroke (SOR: A, based on
      decision analysis of systematic reviews with sensitivity analysis).

PMID- 16451787
TI  - What is the best duration of steroid therapy for contact dermatitis (rhus)?
AB  - Scant evidence exists for the best duration of steroid therapy for contact
      dermatitis due to plants (rhus). Review articles recommend 10 to 21 days of
      treatment with topical or oral corticosteroids for moderate to severe contact
      dermatitis due to plants (strength of recommendation [SOR]: C, based on review
      articles). The primary reason given for the duration of 2 to 3 weeks is to
      prevent rebound dermatitis.

PMID- 16451789
TI  - The power of allele frequency comparisons to detect the footprint of selection in
      natural and experimental situations.
AB  - Recently, inter-population comparisons of allele frequencies to detect past
      selection haven gained popularity. Data from genome-wide scans are used to detect
      the number and position of genes that have responded to unknown selection
      pressures in natural populations, or known selection pressures in experimental
      lines. Yet, the limitations and possibilities of these methods have not been well
      studied. In this paper, the objectives were (1) to investigate the distance over
      which a signal of directional selection is detectable under various scenarios,
      and (2) to study the power of the method depending on the properties of the used
      markers, for both natural populations and experimental set-ups. A combination of
      recurrence equations and simulations was used. The results show that intermediate
      strength selection on new mutations can be detected with a marker spacing of
      about 0.5 cM in large natural populations, 200 to 400 generations after the
      divergence of subpopulations. In experimental situations, only strong selection
      will be detectable, while markers can be spaced a few cM apart. Adaptation from
      standing variation in the base population will be hard to detect, though some
      solutions are presented for experimental designs.

PMID- 16451790
TI  - An efficient variance component approach implementing an average information REML
      suitable for combined LD and linkage mapping with a general complex pedigree.
AB  - Variance component (VC) approaches based on restricted maximum likelihood (REML)
      have been used as an attractive method for positioning of quantitative trait loci
      (QTL). Linkage disequilibrium (LD) information can be easily implemented in the
      covariance structure among QTL effects (e.g. genotype relationship matrix) and
      mapping resolution appears to be high. Because of the use of LD information, the
      covariance structure becomes much richer and denser compared to the use of
      linkage information alone. This makes an average information (AI) REML algorithm
      based on mixed model equations and sparse matrix techniques less useful. In
      addition, (near-) singularity problems often occur with high marker densities,
      which is common in fine-mapping, causing numerical problems in AIREML based on
      mixed model equations. The present study investigates the direct use of the
      variance covariance matrix of all observations in AIREML for LD mapping with a
      general complex pedigree. The method presented is more efficient than the usual
      approach based on mixed model equations and robust to numerical problems caused
      by near-singularity due to closely linked markers. It is also feasible to fit
      multiple QTL simultaneously in the proposed method whereas this would drastically
      increase computing time when using mixed model equation-based methods.

PMID- 16451791
TI  - A bivariate quantitative genetic model for a linear Gaussian trait and a survival
      trait.
AB  - With the increasing use of survival models in animal breeding to address the
      genetic aspects of mainly longevity of livestock but also disease traits, the
      need for methods to infer genetic correlations and to do multivariate evaluations
      of survival traits and other types of traits has become increasingly important.
      In this study we derived and implemented a bivariate quantitative genetic model
      for a linear Gaussian and a survival trait that are genetically and
      environmentally correlated. For the survival trait, we considered the Weibull log
      normal animal frailty model. A Bayesian approach using Gibbs sampling was
      adopted. Model parameters were inferred from their marginal posterior
      distributions. The required fully conditional posterior distributions were
      derived and issues on implementation are discussed. The two Weibull baseline
      parameters were updated jointly using a Metropolis-Hasting step. The remaining
      model parameters with non-normalized fully conditional distributions were updated
      univariately using adaptive rejection sampling. Simulation results showed that
      the estimated marginal posterior distributions covered well and placed high
      density to the true parameter values used in the simulation of data. In
      conclusion, the proposed method allows inferring additive genetic and
      environmental correlations, and doing multivariate genetic evaluation of a linear
      Gaussian trait and a survival trait.

PMID- 16451792
TI  - Validation of an approximate approach to compute genetic correlations between
      longevity and linear traits.
AB  - The estimation of genetic correlations between a nonlinear trait such as
      longevity and linear traits is computationally difficult on large datasets. A two
      step approach was proposed and was checked via simulation. First, univariate
      analyses were performed to get genetic variance estimates and to compute pseudo
      records and their associated weights. These pseudo-records were virtual
      performances free of all environmental effects that can be used in a BLUP animal
      model, leading to the same breeding values as in the (possibly nonlinear) initial
      analyses. By combining these pseudo-records in a multiple trait model and fixing
      the genetic and residual variances to their values computed during the first
      step, we obtained correlation estimates by AI-REML and approximate MT-BLUP
      predicted breeding values that blend direct and indirect information on
      longevity. Mean genetic correlations and reliabilities obtained on simulated data
      confirmed the suitability of this approach in a wide range of situations. When
      nonzero residual correlations exist between traits, a sire model gave nearly
      unbiased estimates of genetic correlations, while the animal model estimates were
      biased upwards. Finally, when an incorrect genetic trend was simulated to lead to
      biased pseudo-records, a joint analysis including a time effect could adequately
      correct for this bias.

PMID- 16451793
TI  - Mapping quantitative trait loci affecting fatness and breast muscle weight in
      meat-type chicken lines divergently selected on abdominal fatness.
AB  - Quantitative trait loci (QTL) for abdominal fatness and breast muscle weight were
      investigated in a three-generation design performed by inter-crossing two
      experimental meat-type chicken lines that were divergently selected on abdominal
      fatness. A total of 585 F2 male offspring from 5 F1 sires and 38 F1 dams were
      recorded at 8 weeks of age for live body, abdominal fat and breast muscle
      weights. One hundred-twenty nine microsatellite markers, evenly located
      throughout the genome and heterozygous for most of the F1 sires, were used for
      genotyping the F2 birds. In each sire family, those offspring exhibiting the most
      extreme values for each trait were genotyped. Multipoint QTL analyses using
      maximum likelihood methods were performed for abdominal fat and breast muscle
      weights, which were corrected for the effects of 8-week body weight, dam and
      hatching group. Isolated markers were assessed by analyses of variance. Two
      significant QTL were identified on chromosomes 1 and 5 with effects of about one
      within-family residual standard deviation. One breast muscle QTL was identified
      on GGA1 with an effect of 2.0 within-family residual standard deviation.

PMID- 16451794
TI  - Optimum allocation of conservation funds and choice of conservation programs for
      a set of African cattle breeds.
AB  - Although funds for livestock conservation are limited there is little known about
      the optimal allocation of conservation funds. A new algorithm was used to
      allocate Mio US dollar 1, 2, 3, 5 or unlimited funds, discounted over 50 years,
      on 23 African cattle breeds conserved with four different possible conservation
      programs. Additionally, Mio US dollar 1 was preferably allocated to breeds with
      special traits. The conceptional in situ conservation programs strongly involve
      breeders and give them part of the responsibility for the conservation of the
      breed. Therefore, the pure in situ conservation was more efficient than
      cryoconservation or combined in situ and cryoconservation. The average annual
      discounted conservation cost for a breed can be as low as US dollar 1000 to US
      dollar 4400 depending on the design of the conservation program and the economic
      situation of the country of conservation. The choice of the breeds and the
      optimal conservation program and the amount of money allocated to each breed
      depend on many factors such as the amount of funds available, the conservation
      potential of each breed, the effects of the conservation program as well as its
      cost. With Mio US dollar 1, 64% of the present diversity could be maintained over
      50 years, which is 13% more than would be maintained if no conservation measures
      were implemented. Special traits could be conserved with a rather small amount of
      the total funds. Diversity can not be conserved completely, not even with
      unlimited funds. A maximum of 92% of the present diversity could be conserved
      with Mio US dollar 10, leaving 8% of the diversity to unpredictable happenings.
      The suggested algorithm proved to be useful for optimal allocation of
      conservation funds. It allocated the funds optimally among breeds by identifying
      the most suited conservation program for each breed, also accounting for
      differences in currency exchange rates between the different countries.

PMID- 16451795
TI  - Spatial analysis of fatal and injury crashes in Pennsylvania.
AB  - Using injury and fatal crash data for Pennsylvania for 1996-2000, full Bayes (FB)
      hierarchical models (with spatial and temporal effects and space-time
      interactions) are compared to traditional negative binomial (NB) estimates of
      annual county-level crash frequency. Covariates include socio-demographics,
      weather conditions, transportation infrastructure and amount of travel. FB
      hierarchical models are generally consistent with the NB estimates. Counties with
      a higher percentage of the population under poverty level, higher percentage of
      their population in age groups 0-14, 15-24, and over 64 and those with increased
      road mileage and road density have significantly increased crash risk. Total
      precipitation is significant and positive in the NB models, but not significant
      with FB. Spatial correlation, time trend, and space-time interactions are
      significant in the FB injury crash models. County-level FB models reveal the
      existence of spatial correlation in crash data and provide a mechanism to
      quantify, and reduce the effect of, this correlation. Addressing spatial
      correlation is likely to be even more important in road segment and intersection
      level crash models, where spatial correlation is likely to be even more
      pronounced.

PMID- 16451796
TI  - Contribution of serum response factor and myocardin to transcriptional regulation
      of smoothelins.
AB  - OBJECTIVE: Smoothelin-A and -B isoforms are highly restricted to contractile
      smooth muscle cells (SMCs). Serum response factor (SRF) and myocardin are
      essential for contractile SMC differentiation. We evaluated the contribution of
      SRF/myocardin to transcriptional regulation of smoothelins. METHODS: Rat vascular
      SMCs were transfected with smoothelin-A and smoothelin-B promoter reporter
      constructs and promoter activity was analyzed. The effects of mutations in the
      smoothelin-A promoter CArG-boxes and co-transfections with a myocardin expression
      plasmid were assessed. Electrophoretic mobility shift assays and chromatin
      immunoprecipitations were performed to investigate SRF-binding to the smoothelin
      A CArG-boxes. RESULTS: Smoothelin promoter activity was detected in vascular
      SMCs. Comparative sequence analysis revealed two conserved CArG elements in the
      smoothelin-A promoter that bind SRF as shown by chromatin immunoprecipitation.
      The proximal CArG-near bound SRF stronger than CArG-far in gel shift assays.
      Mutagenesis studies also indicated that CArG-near is more important than CArG-far
      in regulating smoothelin-A promoter activity. Myocardin augmented smoothelin-A
      promoter activity 2.5-fold in a CArG-near-dependent manner. In contrast,
      myocardin had little effect on the smoothelin-B promoter. CONCLUSION: Smoothelin
      A expression is controlled by an intragenic promoter whose activity is, in part,
      dependent on two CArG boxes that bind SRF. Our data show a role for SRF/myocardin
      in regulating smoothelin-A whereas the higher smoothelin-B expression appears to
      be SRF/myocardin-independent.

PMID- 16451797
TI  - Effect of Salmonella minnesota R595 LPS on the dipalmitoylphosphatidyl
      ethanolamine (DPPE)-dipalmitoylglycerol (DPG)-water model membrane system.
AB  - The effect of Salmonella minnesota R595 lipopolysaccharide (LPS) on model
      membrane consisting of a mixture of fully hydrated lipids
      (dipalmitoylphosphatidylethanolamine (DPPE) and dipalmitoylglycerol (DPG)) was
      investigated by differential scanning calorimetry (DSC), small-angle X-ray
      scattering (SAXS) and freeze-fracture methods. The DPPE-DPG/water system forms a
      multilamellar arrangement in the gel phase which transforms into a mixture of
      inverted hexagonal and cubic structures. By the presence of LPS the thermotropic
      behaviour of the system was affected significantly only at its high concentration
      (1:1 mol/mol LPS/DPPE-DPG) in the gel phase, while above the chain melting
      transition the ratio of the inverted cubic and the hexagonal structures was
      changed and at the 1:1 mol/mol LPS/DPPE-DPG ratio a complex and amorphous phase
      was formed. The structural parameters of the inverted hexagonal and cubic phases
      are modified by the temperature and also by the LPS concentration, as deduced
      from the characteristic SAXS curves. Summarizing the effects of the LPS molecules
      on the DPPE-DPG/water vesicle system a schematic phase diagram was constructed.

PMID- 16451798
TI  - Protective effect of lipoic acid on cyclophosphamide-induced testicular toxicity.
AB  - BACKGROUND: Cyclophosphamide (CP), a widely used anticancer and immunosuppressive
      drug causes severe testicular toxicity. We investigated the protective effect of
      lipoic acid in CP-induced testicular toxicity. METHODS: Two groups of male Wistar
      rats (140+/-20 g) were administered CP (15 mg/kg body weight, oral gavage) once a
      week for 10 weeks to induce testicular toxicity; one of these groups received
      lipoic acid treatment (35 mg/kg body weight, i.p., 24 h prior to CP
      administration) once a week for 10 weeks. A vehicle treated control and a lipoic
      acid control groups were also included. RESULTS: The untreated CP exposed rats
      showed a significant increase in testicular reactive oxygen species (ROS) level,
      along with a significant decrease in cellular thiol levels. The activities of
      testicular marker enzymes such as gamma-glutamyl transferase, beta-glucuronidase,
      acid phosphatase and alkaline phosphatase were increased whereas the activities
      of sorbitol dehydrogenase and lactate dehydrogenase-X were decreased
      significantly in the animals treated with CP. In contrast, rats pretreated with
      lipoic acid showed normal marker enzymic patterns and normal levels of ROS and
      thiols. Testicular protection by lipoic acid is further substantiated by the
      normal histologic findings as against shrunken seminiferous tubules with impaired
      spermatogenesis in the CP administered rats. CONCLUSIONS: By the reversal of
      biochemical and morphological changes towards normalcy, the cytoprotective role
      of lipoic acid is illuminated in CP-induced testicular toxicity.

PMID- 16451800
TI  - Inhibition of Rho-kinase normalizes nonspecific hyperresponsiveness in passively
      sensitized airway smooth muscle preparations.
AB  - Currently, little is known about mechanisms underlying passive sensitization
      induced nonspecific airway hyperresponsiveness. We sought to determine whether
      the nonspecific airway hyperresponsiveness observed after passive sensitization
      involves an increased role of Rho-kinase in airway smooth muscle contraction. In
      addition, the contribution of Rho-kinase to specific allergen-induced airway
      smooth muscle contraction was studied. Guinea pig tracheal smooth muscle
      preparations were incubated for 16 h, in the presence of serum obtained from
      nonsensitized guinea pigs or atopic serum obtained from actively ovalbumin
      sensitized guinea pigs. After incubation, the contribution of Rho-kinase to
      histamine-, methacholine- or ovalbumin-induced isometric contractions was
      determined, using the specific Rho-kinase inhibitor Y-27632. Maximal contractions
      induced by histamine and methacholine were significantly increased in passively
      sensitized preparations, without a change in potency (-logEC50). In control
      preparations, Y-27632 reduced the potency of both agonists, without affecting
      maximal contraction. Remarkably, the increased agonist responsiveness induced by
      passive sensitization was fully normalized by Y-27632. Treatment with Y-27632
      also reduced ovalbumin-induced contraction in these preparations. This study
      shows that the nonspecific airway smooth muscle hyperresponsiveness as well as
      the specific allergen responsiveness induced by passive sensitization are
      dependent on Rho-kinase. The complete inhibition by Y-27632 of the passive
      sensitization-induced increased responsiveness toward histamine and methacholine
      indicates a pivotal role of Rho-kinase in this process.

PMID- 16451799
TI  - Penicillamine administration reverses the inhibitory effect of
      hyperhomocysteinaemia on endothelium-dependent relaxation and superoxide
      formation in the aorta of the rabbit.
AB  - Although hyperhomocysteinaemia is a risk factor for cardiovascular disease, the
      mechanisms underlying this association have not been elucidated. It has been
      demonstrated, however, that copper augments the inhibitory effect of homocysteine
      on nitric oxide (NO)-mediated relaxation of the rat aorta through increased
      superoxide formation, which reacts with NO thereby reducing the bioavailability
      of NO. Since it follows that the administration of a copper chelator may blunt
      the pathogenic impact of hyperhomocysteinaemia, in vivo, the effect of
      penicillamine administration on NO-dependent relaxation and superoxide formation
      in the aortae of hyperhomocysteinaemic rabbits was studied. New Zealand White
      rabbits were fed a methionine-rich (20 g/kg chow) diet for 1 month+/
      penicillamine administered orally (10 mg/kg/day) and aortic relaxation elicited
      with acetylcholine and superoxide measured. The role of NADPH oxidase was also
      studied using a range of inhibitors and western analysis of gp47(phox) (a
      catalytic subunit of NADPH oxidase). The methionine-rich diet markedly increased
      plasma total homocysteine levels. In hyperhomocysteinaemic rabbits there was a
      marked reduction of acetylcholine-stimulated relaxation and an increase in
      superoxide formation that were both inhibited with superoxide dismutase and
      apocynin, an NADPH oxidase inhibitor. Gp47(phox) expression was also increased in
      aortae from methionine fed rabbits. Penicillamine administration significantly
      reduced plasma total copper in methionine-fed rabbits compared to controls.
      Impaired acetylcholine-stimulated relaxation, increased superoxide formation and
      increased gp47(phox) expression in aortae from methionine-fed rabbits was
      reversed by penicillamine administration. These data indicate that
      hyperhomocysteinaemia augments the formation of arterial superoxide through an
      increase in NADPH oxidase expression/activity which in turn reduces NO
      bioavailability. Since these effects were reversed by penicillamine, these data
      consolidate the hypothesis that copper plays a role in mediating homocysteine
      induced vasculopathy.

PMID- 16451801
TI  - Application of ultra performance liquid chromatography-tandem mass spectrometry
      to the analysis of priority pesticides in groundwater.
AB  - Ultra performance liquid chromatography coupled to triple quadrupole tandem mass
      spectrometry (UPLC-MS/MS) has been applied for the accurate and rapid analysis of
      nine trace level priority pesticides in water. The UPLC technology, based on the
      use of columns packed with 1.7 microm porous particles combined with higher
      pressures than those conventionally applied in HPLC, enabled to improve in peak
      resolution, sensitivity and speed of analysis. UPLC chromatograms showed very
      sharp peaks with less than 2 s wide at the base, except for alachlor. This
      enhanced efficiency resulted in an increased separation speed of the whole UPLC
      MS/MS procedure that required less than 5 min. Limits of detection, determined
      for 300 ml water samples after SPE preconcentration were in the range between 0.1
      and 20 ng/L. The presence of matrix effects or ion suppression was checked by the
      obtaining of calibration curves in both pure solvent and matrix matched
      standards. Other performance characteristics of the method, such as linearity and
      precision were also satisfactory. Finally, the method was successfully applied to
      the analysis of two water samples from an inter-laboratory exercise.

PMID- 16451802
TI  - Processing gas chromatographic data and confidence interval calculation for
      partition coefficients determined by the phase ratio variation method.
AB  - The phase ratio variation (PRV) method is widely used for the determination of
      partition coefficient values (dimensionless Henry's law constants) by headspace
      gas chromatography. Traditional data processing by linear regression has several
      drawbacks: potential bias introduced by linearization, absence of quality
      indicator of the resulting value and, in case of replicate determinations, poor
      utilisation of the existing measurements leading to unnecessarily large
      confidence intervals. The paper compares existing PRV data processing methods
      (linear and nonlinear regression, parametric) and derives confidence intervals
      for the resulting partition coefficient values. The possibility of using several
      series of measurements to derive a single partition coefficient value with
      tighter and more reliable confidence intervals is presented for all three
      processing methods. The methods are tested on published literature data and new
      experimental data for 12 volatile organic compounds in water at 25 degrees C. The
      nonlinear regression based on several series of measurements appears to be the
      method of choice.

PMID- 16451803
TI  - Chromatographic determination of plant saponins--an update (2002-2005).
AB  - The developments during 2002-2005 in the methods used for saponin analyses in
      plant material are presented. There were number of papers published on isolation
      and identification of new saponins by chromatographic techniques. Some new
      developments can be found in separation techniques or solid and mobiles phases
      used. Separation of individual saponins is still complicated and time consuming.
      This is due to the fact that in most of the plant species saponins occur as a
      multi-component mixture of compounds of very similar polarities. Thus, to isolate
      single compound for structure elucidation or biological activity testing, a
      combination of different chromatographic techniques has to be used, e.g. first
      separation of the mixture to simpler sub-fractions on reversed phase C18 has to
      be followed by further purification on normal phase Silica gel column. Especially
      difficult is determination of saponins in plant material as these compounds do
      not possess chromophores and their profiles cannot be registered in UV. Most HPLC
      methods apply not only specific registration at 200-210 nm, but these methods are
      not applicable for determination of many saponins in plant material at levels
      lower than 200-300 mg/kg. Some new or improved techniques for quantification of
      saponins in plant material were published in reviewed period. These include
      further progress in the application of evaporative light scattering detection
      (ELSD) for saponin profiling and quantification, which is also not only specific
      but also more sensitive in comparison to 200-210 nm detection. Some progress in
      development of new applications for liquid chromatography-electrospray mass
      spectrometry (LC/ESI/MS) for saponin determination has also been done. This
      method gives highest sensitivity and on line identification of separated saponins
      and should be recommended for specialized analyses of extracts and pharmaceutical
      formulas like the validation of a new assay. From non-chromatographic techniques
      for saponin determination, a sensitive and compound specific ELISA tests for some
      saponins were developed.

PMID- 16451804
TI  - Selective extraction of organophosphorus nerve agent degradation products by
      molecularly imprinted solid-phase extraction.
AB  - The analysis of alkyl alkylphosphonic acids, the degradation products of V and G
      nerve agents as VX, Sarin or Soman, is an important task for the verification of
      compliance to the Chemical Weapons Convention. The detection of these
      contaminants at low concentration levels is often difficult in complex matrices
      due to the amount of interfering substances. Molecularly imprinted solid-phase
      extraction technique should allow a selective extraction of these compounds from
      complex samples, and thus make their detection easier. Two molecularly imprinted
      polymers (MIPs) prepared with methacrylic acid (MAA) as monomer and pinacolyl
      methylphosphonic acid (PMPA) as template molecule were synthesised and tested.
      The first polymer, MIP A, was prepared with ethylene glycol dimethacrylate
      (EGDMA) in dichloromethane. The second polymer, MIP B, was synthesised using
      trimethylolpropane trimethacrylate (TRIM) in acetonitrile. To evaluate the
      selectivity provided by these MIPs, the retention of the ethyl methylphosphonic
      acid (EMPA) target molecule was studied in parallel on a non-imprinted polymer
      (NIP). While MIP A does not show any difference compared to NIP A, a good
      selectivity was obtained for MIP B. After the optimisation of the extraction
      process, 60% of EMPA can be removed from the NIP B without affecting the
      retention on the MIP B. A recovery of extraction of 93% was then obtained on the
      MIP B. Its capacity was then measured and corresponds to 97 microg of EMPA per
      gram of MIP. Finally, the selectivity of MIP B was clearly demonstrated by
      applying it to the clean-up of a soil extract spiked with EMPA.

PMID- 16451805
TI  - Toward a better understanding of cerebral plasticity in multiple sclerosis.

PMID- 16451806
TI  - Distribution of survival times of deliberate Plasmodium falciparum infections in
      tertiary syphilis patients.
AB  - Survival time data of Plasmodium falciparum infections from deliberate infection
      of human subjects with P. falciparum between 1940 and 1963 as a treatment for
      neurosyphilis in the USA (Georgia) have been used to test the fits of five
      commonly used parametric distributions for survival times using quantile-quantile
      plots. Our results suggest that the best fit is obtained from the Gompertz or
      Weibull distributions. This result has important implications for mathematical
      modelling of malaria, which has for the past century exclusively assumed that the
      duration of malaria infections has an exponential distribution. It is desirable
      to know the correct distribution because its shape profoundly influences the
      length of monitoring needed in an intervention programme for eliminating or
      reducing malaria.

PMID- 16451807
TI  - Effects of the A 2A adenosine receptor antagonist KW6002 in the nucleus accumbens
      in vitro and in vivo.
AB  - In this study, we have used the selective A 2A adenosine receptor antagonist
      KW6002 to investigate the function of A 2A receptors in the Lister hooded rat
      nucleus accumbens in vitro and in vivo. Radioligand binding studies confirmed a
      greater than 50-fold selectivity of KW6002 for A 2A receptors compared to A1
      receptors. Release of [3H]-dopamine from nucleus accumbens slices in vitro was
      almost doubled in the presence of 300 nM KW6002, while GABA release was inhibited
      by approximately one third. In vivo, intraperitoneal administration of KW6002 (4
      mg kg(-1)) increased dopamine overflow almost 4-fold in the nucleus accumbens. In
      behavioural testing, KW6002 elicited place preference and increased locomotor
      activity at 1, 2 and 4 mg kg(-1). Taken together, these results suggest a role
      for tonic activation of A 2A adenosine receptors in reward-related phenomena.

PMID- 16451809
TI  - Ca2+ permeability through rat cloned alpha9-containing nicotinic acetylcholine
      receptors.
AB  - We investigated the functional properties of rat alpha9 and alpha9alpha10
      nicotinic acetylcholine receptors (nAChRs) expressed by transient transfection in
      the rat GH4C1 cell line, using both Ca(2+) imaging and whole-cell recording.
      Acute applications of ACh generated short-delay fast-rising and quick-decaying
      Ca(2+) transients, suppressed in Ca(2+)-free medium and invariably accompanied by
      the activation of whole-cell inward currents. The mean amplitude of ACh-induced
      currents was as small as -16 pA in alpha9 subunit cDNA-transfected GH4C1 cells
      (alpha9-GH4C1), while they were much larger (range: -150 to -300 pA) in
      alpha9alpha10 subunit cDNAs-transfected GH4C1 cells (alpha9alpha10-GH4C1).
      Currents were not activated by nicotine, were blocked by methyllycaconitine and
      were ACh concentration-dependent. Because the Ca(2+) permeability of alpha9
      containing nAChRs has been estimated in immortalized cochlear UB/OC-2 mouse
      cells, we also characterized the ACh-induced responses in these cells. Unlike
      alpha9- and alpha9alpha10-GH4C1 cells, UB/OC-2 cells responded to ACh with both
      long-delay methyllycaconitine-insensitive whole-cell currents and long-lasting
      Ca(2+) transients, the latter being detected in the absence of Ca(2+) in the
      extracellular medium and being suppressed by the Ca(2+)-ATPase inhibitor
      thapsigargin, known to deplete IP(3)-sensitive stores. These results indicated
      the involvement of muscarinic nAChRs and the lack of functional ACh-gated
      receptor channels in UB/OC-2 cells. Thus, we measured the fractional Ca(2+)
      current (P(f), i.e. the percentage of total current carried by Ca(2+) ions) in
      alpha9alpha10-GH4C1, obtaining a P(f) value of 22 +/- 4%; this is the largest
      value estimated to date for a ligand-gated receptor channel. The physiological
      role played by Ca(2+) entry through alpha9-containing nAChRs gated by ACh is
      discussed.

PMID- 16451808
TI  - Comparison of kinetic constants of creatine kinase isoforms.
AB  - The purpose of this study was to elucidate the functional differences between the
      CK isoforms by cloning the cDNAs of 12 CK isoforms: the M and B cytoplasmic forms
      and uMiCK from mouse, the M1, M2 and B cytoplasmic forms from Danio rerio, M1 and
      M2 cytoplasmic forms from the lower vertebrate Lampetra japonica, a cytoplasmic
      CK and a MiCK from the marine worm Neanthes diversicolor, and a cytoplasmic CK
      and a MiCK from the soft coral Dendronephthya gigantea. These were expressed in
      Escherichia coli as a fusion protein with maltose-binding protein, and kinetic
      constants (K(m), K(d) and k(cat)) of all the recombinant enzymes, except for the
      unstable Dendronephthya cytoplasmic CK, were determined for the forward reaction.
      The kinetic constants of the M- and B-forms of the mouse and Danio cytoplasmic
      CKs differed significantly, with the K(m) for creatine (K(m)Cr) of M-CK being
      three- to nine-fold higher than that of B-CK, possibly reflecting differences in
      the concentration of creatine in muscle and brain cells. The mouse uMiCK had the
      lowest K(m)Cr value among the CK isoforms. In addition, it also exhibited a
      strong synergism for substrate binding (K(d)/K(m)=11.8). These results indicate
      that uMiCK has unique characteristics compared with other CK isoforms. Two
      subisoforms of M-CK were found in the lower vertebrate L. japonica, and the
      kinetic constants of recombinant M1- and M2-CKs differed significantly. The M1-
      and M2-CKs were expressed in skeletal muscle with a ratio of 7:3, while M1-CK was
      the predominant subisoform in the testis. The kinetic constants of cytoplasmic CK
      from the marine worm Neanthes were significantly different from those of Neanthes
      MiCK, possibly indicating that functional differences among CK isoforms occurred
      at least before the divergence of annelids from other protostome invertebrates.

PMID- 16451811
TI  - Outcomes of a computer-based cognitive rehabilitation program on Alzheimer's
      disease patients compared with those on patients affected by mild cognitive
      impairment.
AB  - The aim of the present study is to evaluate the outcomes of a computer-based
      cognitive training on patients affected by Alzheimer's disease (AD) compared with
      the outcomes on patients affected by mild cognitive impairment (MCI), multiple
      system atrophy (MSA). Ten AD patients aged 74.1+/-5.6 years, with mini-mental
      state examination (MMSE) score at baseline of 23.9+/-2.4, and 10 MCI patients
      aged 70.6+/-6.0 years, with MMSE score of 28.0+/-1.4, attending our day-hospital
      of neurorehabilitation were selected for the study. Three MSA patients aged
      69.0+/-9.5 years, MMSE scores 26.7+/-2.3 were selected from the same setting in
      order to have a different control group. Each patient attended two training
      programs and was evaluated according to cognitive and non-cognitive functions at
      baseline at the end of the second training program. The AD group showed a
      significant MMSE score improvement (p=0.010). On the contrary, MMSE scores at
      baseline and at follow-up remained quite stable in the other two groups. AD
      patients also showed significant improvement in the areas of verbal production
      (p=0.036) and executive functions (p=0.050). MCI patients significantly improved
      in behavioral memory (p=0.017; p=0.011). No significant improvement was observed
      in MSA group. Our data seem to indicate that the same individualized
      rehabilitative intervention could have different effects according to patient's
      diagnosis. MCI and AD patients had significant improvements in global cognitive
      status and/or in specific cognitive areas. On the contrary, MSA patients did not
      benefit at all.

PMID- 16451810
TI  - Cerebellar neurotransmission in attention-deficit/hyperactivity disorder: does
      dopamine neurotransmission occur in the cerebellar vermis?
AB  - Children and adolescents with attention-deficit/hyperactivity disorder (ADHD)
      have smaller cerebellar volumes, particularly in the posterior-inferior
      cerebellar vermis (lobules VIII-X). Functional activation of the human cerebellar
      vermis following stimulant administration has also been repeatedly demonstrated.
      There is no well-characterized dopaminergic pathway that projects to the
      posterior-inferior cerebellar vermis, although the dopamine transporter (DAT) and
      tyrosine hydroxylase (TH) have been localized in the posterior-inferior vermis in
      the non-human primate by immunohistochemistry. We hypothesized that DA
      neurotransmission may occur in localized "hot spots" in the cerebellar vermis,
      and if so, that differences in such neurotransmission might be relevant to the
      pathophysiology of ADHD. To investigate this hypothesis, cerebellar tissue was
      obtained from rats and non-human primates. Catecholamines were extracted and
      analyzed using HPLC with coulometric detection. A regional gradient of
      norepinephrine (NE) and DA was found throughout the cerebellum with NE levels
      always roughly 10-40-fold higher than DA in both rats and monkeys. In addition,
      in vivo microdialysis studies were performed in the rat posterior-inferior
      cerebellar vermis in anesthetized animals. Significant NE overflow was observed
      over baseline following reverse microdialysis induced release by potassium or d
      amphetamine. DA overflow was not observed over baseline for potassium
      stimulation, but was significant for d-amphetamine stimulation. These studies
      refute the hypothesis that DA neurotransmission normally occurs in the rat
      cerebellar vermis, but highlight that vermal DA is released by d-amphetamine. The
      presence of DAT may therefore allow for enhanced regulation of NE and not
      regulation of released DA.

PMID- 16451812
TI  - Geographical and temporal aspects of an outbreak of off-flavours in bulk-tank
      milk in Prince Edward Island, Canada.
AB  - The geographical and temporal dynamics of the outbreak of off-flavours in bulk
      tank milk that occurred between September 2000 and June 2002 in Prince Edward
      Island (PEI) dairy herds were described using spatial, temporal and space-time
      scan statistics. Results suggested clustering both in time and space. We found
      one primary cluster (six case herds, feed off-flavour, October 2000 to January
      2001) and two secondary clusters formed of feed (5 case herds, October 2000 to
      January 2001)) and rancid (five case herds, December 2000 to March 2001) off
      flavours, respectively. The relative risk (RR) for producing off-flavoured milk
      was similar for these three clusters (RR=6.4).

PMID- 16451813
TI  - A new and rapid bioassay for the detection of gliotoxin and related
      epipolythiodioxopiperazines produced by fungi.
AB  - Gliotoxin is an immunosuppressive cytotoxin produced by numerous environmental or
      pathogenic fungal species. For this reason, it is one of the mycotoxins which
      must be systematically searched for in samples for biological control. In this
      study, a new, rapid and sensitive method for detecting gliotoxin has been
      developed. This bioassay is based on the induction of morphological changes in
      cultured cells (human KB cell line) by gliotoxin. Interpretation of the assay can
      be carried out after 1 h of incubation, either by direct microscopic observation,
      or with an automated microplate-reader at 630 nm. The limit of detection is 18-20
      ng of gliotoxin in the well, depending on the used observation method. A high
      degree of specificity of the detection is brought about by the ability of the
      reducing reactant dithiothreitol to inhibit the biological activities of
      epipolythiodioxopiperazines (ETPs), such as gliotoxin, by reducing their
      polysulfide bridge. The bioassay allows a rapid primary screening of samples and
      a semi-quantitative evaluation of the gliotoxin concentration in extracts. The
      method has been used to study the gliotoxin production by different fungal
      strains, allowing to highlight 3 strains of Aspergillus fumigatus producing
      gliotoxin in various extracts.

PMID- 16451814
TI  - Why do not patients receive influenza vaccine in December and January?
AB  - BACKGROUND: Influenza vaccination levels in older patients have changed little
      since the mid-1990s. Despite frequent health care visits by a majority of older
      persons, many missed opportunities continue to occur. METHODS: Patients were
      eligible for the study if they were age 50 and older, had not received influenza
      vaccine during the current season and were making a scheduled visit to one of the
      13 study sites in California, New York, or New Mexico for purposes other than
      vaccination. Through direct observation, we determined if office staff inquired
      about vaccination status, discussed vaccination, or both. We defined missed
      opportunities as failure to administer influenza vaccine to patients for whom it
      was indicated. RESULTS: Missed opportunities increased steadily from October to
      January (P < 0.0001), and were more common when there was no inquiry or
      discussion (P < 0.00001), among patients aged 50-64 (P < 0.0001) and in
      California and New Mexico (P = 0.001). A classification tree analysis revealed
      that lack of inquiry and week of visit contributed most to missed opportunities.
      DISCUSSION: Early in the vaccination season, missed opportunities were uncommon
      and specific inquiries into or discussion of vaccination did not appear
      necessary. In December and January, patients tended to be vaccinated only when
      vaccination was addressed during the visit. Efforts to remind patients about
      vaccination later in the vaccination season may be essential to achieving higher
      coverage in the U.S.

PMID- 16451815
TI  - Glial fibrillary acidic protein expression after electroconvulsive shocks in rat
      brain.
AB  - OBJECTIVE: The aim of the present study was to assess the effect of
      electroconvulsive shock (ECS) in glial fibrillary acidic protein (GFAP)
      expression in rat brain. METHODS: Rats were given either a single (acute) or a
      series of eight (chronic) ECS. Brain regions were isolated and levels of glial
      fibrillary acidic protein (GFAP) in the brain tissue (cortex, hippocampus, and
      cerebellum) were assessed using an enzyme-linked immunosorbent assay (ELISA).
      RESULTS: We showed that GFAP expression is reduced in the hippocampus within 48 h
      and 7 days after acute ECS. GFAP levels are increased in the cerebellum
      immediately after acute and chronic ECS. No changes were observed in the cortex.
      CONCLUSIONS: Our findings showed a differential effect of acute and chronic ECS
      in the astroglial response in the brain of rats.

PMID- 16451816
TI  - Effect of selenium-containing compounds on hepatic chemoprotective enzymes in
      mice.
AB  - Selenite and organoselenium compounds have been examined at supranutritional
      levels for their ability to influence the activity and mRNA levels of
      chemoprotective enzymes in the livers of selenium-sufficient mice and the changes
      compared to those elicited by oltipraz. Compounds investigated included novel
      selenocysteine prodrugs that have previously been evaluated for their ability to
      reduce the tumorigenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      in mice. Following seven daily doses (i.g.), all compounds except 2
      methylselenazolidine-4(R)-carboxylic acid (MSCA) increased thioredoxin reductase
      activity (43-92%) but only for 2-oxoselenazolidine-4(R)-carboxylic acid (OSCA)
      was there an accompanying increase in mRNA. No compound enhanced glutathione
      peroxidase activity, although sodium selenite significantly elevated the mRNA of
      this enzyme. Oltipraz was an efficacious inducer of both thioredoxin reductase
      and glutathione peroxidase mRNAs. Sodium selenite, selenazolidine-4(R)-carboxylic
      acid (SCA), and OSCA elevated NAD(P)H-quinone oxidoreductase mRNA but only for
      OSCA was the elevation in mRNA accompanied by an increase in enzyme activity. L
      Selenocystine significantly increased this activity without increasing mRNA
      levels. Sodium selenite, L-selenocystine, L-selenomethionine, and Se-methyl-L
      selenocysteine all enhanced glutathione S-transferase activity. The increased
      activity with sodium selenite was accompanied by increases in mRNAs of Gst alpha,
      Gst mu and Gst pi classes, while for L-selenocystine and Se-methyl-L
      selenocysteine, only an elevation in the mRNA for the Gst alpha class was
      observed. Gst alpha and Gst mu class mRNAs were elevated by OSCA without a
      significant elevation in enzyme activity. SCA and MSCA both elevated a Gst pi
      mRNA and MSCA elevated Gst mu in addition. By comparison, oltipraz only
      significantly elevated the mRNA of Gst mu, adding to the conclusion that across
      the entire study, no selenium compound appears to be acting purely through the
      antioxidant response typified by oltipraz. Despite their chemical similarity, the
      three cysteine prodrugs, SCA, MSCA, and OSCA, each produced its own unique
      pattern of effects on protective enzymes and none was identical to the pattern
      elicited by sodium selenite, L-selenocystine, L-selenomethionine, and Se-methyl-L
      selenocysteine. The study also shows that after 7 days of administration, there
      was only occasional concordance between elevations in mRNA and enzyme activity
      for any selenium compound and for any protective enzyme, there was no response in
      common for all selenium compounds.

PMID- 16451817
TI  - Molecular overlap of fly circadian rhythms and human pancreatic cancer.
AB  - Circumstantial evidence demonstrating a role for circadian rhythms in cancer has
      been presented but there is little direct molecular evidence to support this idea
      in human cancer. Herein, we report a significant similarity between fly genes
      with strong circadian rhythms and human genes under expressed in pancreatic
      cancer. The list of genes includes both circadian regulator genes, such as period
      1 and DEC1, and downstream effectors, such as ubiquitin specific protease 30.
      This observation may indicate that the pancreas peripheral clock is disrupted in
      pancreatic cancer and are consistent with the recent proposals that circadian
      genes act as tumor suppressors.

PMID- 16451818
TI  - A robust central venous line dressing for use in burns.

PMID- 16451819
TI  - Free flap survival despite severe anemia after fourth degree hand burn.

PMID- 16451820
TI  - Resuscitation fluid volume and abdominal compartment syndrome in patients with
      major burns.
AB  - Abdominal compartment syndrome (ACS) is rarely reported as a complication of
      severe burn. This study clarified the risk of burned patients with and without
      ACS, especially regarding the resuscitation fluid volume. Extensively burned
      patients admitted to our burn unit from January 2003, through to June 2004, were
      examined. Vital signs, blood gas analysis, bladder pressure to estimate intra
      abdominal pressure (IAP), peak inspiratory pressure (PIP), resuscitation fluid
      volume, and urine output (UO) were analyzed. Intra-abdominal hypertension (IAH)
      was defined as an IAP of more than 30 cm of H2O. Eight of 48 patients suffering
      from a more than 30% total burn surface area developed ACS in 18.3+/-4.9 h. In
      these patients, IAP (49+/-12 cmH2O), PIP (50+/-16 cmH2O), heart rate (115+/
      8/min), and PaCO2 (54.6+/-10.1 mmHg) were higher than normal, and their
      resuscitation volume was 0.40+/-0.11 L/kg. Also, a significant correlation
      between the IBP, PIP and resuscitation volume was observed. Most patients with
      severe burns required more than 300 mL/kg of resuscitation fluid for the first 24
      h after injury that led to ACS and had higher HR, IBP, PIP and PaCO2 despite
      arterial pressure showing no significant difference.

PMID- 16451821
TI  - Autonomy (vs. sociotropy) and depressive symptoms in quitting smoking: evidence
      for trait-congruence and the role of gender.
AB  - According to Beck's cognitive theory of depression, autonomy (high achievement
      concerns) and sociotropy (high interpersonal concerns) are vulnerability factors
      for depression when achievement or interpersonal stressors, respectively, are
      experienced. This hypothesis was tested among men and women attempting to quit
      smoking, an achievement stressor that can provoke depressive symptoms. Smokers
      recruited from the community (N=210) provided information about their quit
      attempt through mailed questionnaires. For the 48-h period following the quit,
      relationships among autonomy, sociotropy, coping, depressive symptoms and lapsing
      were assessed. Structural equation models supported the trait-congruence
      hypothesis because greater autonomy, but not sociotropy, was associated with
      elevated depressive symptoms among both men and women smokers. However, results
      were stronger for men (beta=.47, p=.0001) than for women (beta=.20, p=.05). After
      accounting for autonomy's relationship with depressive symptoms, greater autonomy
      was inversely associated with lapsing among men (beta=-.35, p=.01), but not
      women. Results point to the potential usefulness of a theoretical approach to
      understanding relationships between depressive symptoms and smoking cessation,
      and indicate that autonomous personality may be an important factor in smoking
      cessation in men.

PMID- 16451822
TI  - HMGN1 is dispensable for myogenesis and adipogenesis.
AB  - Expression of key regulatory and tissue specific proteins necessary for
      myogenesis and adipogenesis are dependent on functional SWI/SNF enzymes that
      hydrolyze ATP to remodel chromatin and allow factors access to chromatinized DNA.
      Functional chromatin structural changes also can be facilitated by the high
      mobility group-N1 (HMGN1) protein. HMGN1 is a chromatin architectural protein
      that specifically interacts with nucleosomes and has been shown to facilitate the
      reversal of repressive chromatin structure, thereby making it more conducive for
      transcription. To determine if HMGN1 functions in myogenesis or adipogensis, two
      SWI/SNF-dependent processes, we used RNA interference to created stable cell
      lines with reduced HMGN1 protein levels and differentiated them along the
      myogenic and adipogenic pathways. We show that neither myogenesis nor
      adipogenesis was affected by reduced HMGN1 protein levels. We further demonstrate
      that HMGN1 levels naturally decrease as a function of contact-mediated cell cycle
      arrest, thereby explaining the lack of requirement for HMGN1 in these cellular
      differentiation processes.

PMID- 16451823
TI  - Limonene GP1/PG organogel as a vehicle in transdermal delivery of haloperidol.
AB  - Penetration enhancers are a classical means for improving transdermal drug
      delivery (TDD). Enhancers permeate into the skin and reversibly decrease the
      barrier resistance. Basically, our aim is to formulate a transdermal gel
      containing an appropriate enhancer for a controlled drug release. Terpenes,
      namely limonene, linalool and cineole, in propylene glycol (PG) were first
      investigated in vitro for their capacity to enhance the percutaneous release of
      an anti-psychotic drug, haloperidol (HP). Relative to oxygenated linalool and
      cineole, hydrocarbon limonene was more effective as a skin enhancer; it increased
      human skin permeability and decreased lag time. Limonene was thus incorporated in
      an organogel comprised of gelator GP1 and PG. This skin-friendly gel in a
      transdermal patch could act as a long-acting formulation that delivers HP at a
      sustained percutaneous rate. The microscopic framework of the organogel is a
      branched network of interlocking fibres. Varying the gelator content modulates
      the fibre density and gel stiffness, and presents different degrees of resistance
      to drug diffusion on the vehicle side. Rheological and permeation studies
      demonstrated that an increase in gelator concentration increased gel moduli and
      decreased drug flux simultaneously. The rheology of the gel matrix influenced
      drug release rate in a manner described by several experimentally-derived
      correlations.

PMID- 16451824
TI  - Oral delivery of beta-lactamase by Lactococcus lactis subsp. lactis transformed
      with Plasmid ss80.
AB  - The objective was to use normal flora to deliver protein/peptide drugs orally. A
      probiotic bacterium, Lactococcus lactis subsp. lactis (L. lactis) transformed
      with Plasmid ss80, which made it able to synthesize and secrete beta-lactamase, a
      29 kDa protein, was used as the delivery system for beta-lactamase. Oral
      absorption of beta-lactamase in rats when delivered by this L. lactis system was
      investigated. The oral bioavailability of beta-lactamase delivered by 3x10(7) of
      the L. lactis was equivalent to 209 mU of i.v. dose, and the estimated relative
      bioavailability was 16.7%. When delivered by beta-lactamase free solution form,
      the relative oral bioavailability was 4.7%, which increased to 6.0% when co
      administered with 3x10(7) of the untransformed L. lactis. The results
      demonstrated that the L. lactis significantly increased the beta-lactamase oral
      bioavailability by 2-3-folds (p<0.01), the mean residence time (MRT) by 3-4 times
      (p<0.01), and the mean absorption time (MAT) by 6-14 times (p<0.01), as compared
      to the free solution form with/without the untransformed L. lactis. In
      conclusion, the L. lactis is more efficient in delivering beta-lactamase orally
      compared with the free solution form. It also provides a sustained delivery
      mechanism for beta-lactamase. Gene-transformed normal flora may be used as an
      efficient and sustained delivery system for protein drugs through oral route.

PMID- 16451825
TI  - State-of-the-art ultrasonography of hepatocellular carcinoma.
AB  - Over the last few decades sonographic techniques have progressed remarkably.
      Recent advances in ultrasonography include harmonics, real-time spatial compound
      imaging, adaptive image processing, 3D power Doppler imaging and contrast
      enhanced gray-scale harmonic ultrasonography. These advances have had positive
      effects on the diagnosis of hepatocellular carcinomas and on the evaluation of
      their responses to therapy. In this article, we review recent sonographic
      advances for the diagnosis and treatment of hepatocellular carcinomas and its
      typical imaging features.

PMID- 16451826
TI  - Identification of Mycobacterium marinum macrophage infection mutants.
AB  - Mycobacterium marinum is an important pathogen of humans, amphibians and fish.
      Most pathogenic mycobacteria, including M. marinum, infect, survive and replicate
      primarily intracellularly within macrophages. We constructed a transposon mutant
      library in M. marinum using Tn5367 delivered by phage transduction in the shuttle
      phasmid phAE94. We screened 529 clones from the transposon library directly in
      macrophage infection assays. All clones were screened for their ability to
      initially infect macrophages as well as survive and replicate intracellularly. We
      identified 19 mutants that fit within three classes: class I) defective for
      growth in association with macrophages (42%), class II) defective for macrophage
      infection (21%) and class III) defective for infection of and growth in
      association with macrophages (37%). Although 14 of the macrophage infection
      mutants (Mim) carry insertions in genes that have not been previously identified,
      five are associated with virulence of mycobacteria in animal models. These
      observations confirm the utility of mutant screens directly in association with
      macrophages to identify new virulence determinants in mycobacteria. We
      complemented four of the Mim mutants with their M. tuberculosis homologue,
      demonstrating that secondary mutations are not responsible for the observed
      defect in macrophage infection. The genes we identified provide insight into the
      molecular mechanisms of macrophage infection by M. marinum.

PMID- 16451827
TI  - Molecular cDNA cloning and analysis of the organization and expression of the IL
      1beta gene in the Nile tilapia, Oreochromis niloticus.
AB  - The full-length cDNA sequence of interleukin-1beta (IL-1beta) from the Nile
      tilapia, Oreochromis niloticus, was determined by using PCR with primers designed
      from known fish IL-1beta sequences followed by elongation of the 5' and 3' ends
      using Rapid Amplification of cDNA Ends (RACE). The cDNA contains a 92-bp 5'
      untranslated region (UTR), a single open reading frame (ORF) of 732 bp that
      translates into a 243-amino acid molecule, a 341-bp 3' UTR with four cytokine RNA
      instability motifs (ATTTA), and a polyadenylation signal (AATAAA) at 15
      nucleotides upstream of the poly(A) tail. The organization of the genomic IL
      1beta based on the cDNA sequence appeared to be 4 introns and 5 exons. In
      comparison with known IL-1beta amino acid sequences, including human, catshark,
      trout, turbot, carp, sea bream, sea bass and goldfish, the amino acid sequence
      deduced from the cDNA sequence of Nile tilapia showed different levels of
      identity ranging from 25.32% to 66.80% and homology ranging from 41.88% to
      82.19%. Although the entire cDNA sequence of Nile tilapia IL-1beta showed from
      49.45% to 67.05% identity to those of other reported IL-1beta cDNAs, each exon
      also showed different levels of identity to the corresponding exons of other
      reported IL-1beta cDNAs. The highest nucleotide sequence identity for exon 1 and
      exons 2-5 of Nile tilapia IL-1beta was found in the corresponding exons of sea
      bream and sea bass, respectively. After in vitro stimulation with
      lipopolysaccharide (LPS), we found an increased level of IL-1beta expression in
      head kidney cells compared to that of unstimulated cells. However, this
      difference was no longer apparent after 4 h of stimulation, at which time the
      levels were similar in stimulated and unstimulated cells. Head kidney cells
      stimulated in vivo by an intraperitoneal injection of LPS showed a peak level of
      IL-1beta expression after 1 day and a decreased level after 3 days. At 7 days
      after stimulation, we were hardly able to detect IL-1beta expression.

PMID- 16451828
TI  - Profibrotic cytokines and lymphocyte proliferation in stable renal allograft
      recipients treated with or without cyclosporine A.
AB  - Profibrotic cytokines such as transforming growth factor-beta 1 (TGF-beta1) and
      endothelin-1 (ET-1) are involved in the pathogenesis of chronic allograft
      nephropathy. We assessed the effect of maintenance immunosuppression with or
      without cyclosporine A on TGF-beta1 and ET-1 expression as well as lymphocyte
      proliferation in renal allograft recipients. Patients were divided into groups
      according to their maintenance immunosuppression: A, azathioprine +
      methylprednisolone; B, cyclosporine A + azathioprine + methylprednisolone. TGF
      beta1 and ET-1 plasma concentrations were not different between both groups. TGF
      beta1 concentrations in cell culture supernatants and lymphocyte proliferation
      were higher in group B as compared to group A. No correlation was found between
      TGF-beta1 plasma concentrations and lymphocyte proliferation. Multiple linear
      regression analysis revealed that patient characteristics influence TGF-beta1 and
      ET-1 expression. In conclusion, plasma levels of profibrotic cytokines do not
      reflect the existing profibrotic potential of immunosuppressive drugs.
      Demographic factors and the employed co-medication confound the results.

PMID- 16451829
TI  - Platypnoea orthodeoxia in a patient with aortic root dilatation and a patent
      foramen ovale.
AB  - Platypnoea orthodeoxia syndrome is a rare condition in which shortness of breath
      and hypoxaemia occur when upright and resolve when prone. The hypoxaemia results
      from increased right to left shunting of deoxygenated blood, when standing,
      through a patent foramen ovale (PFO), atrial septal defect (ASD) or other right
      to left shunt, in the absence of raised right-heart pressure. We present the case
      of a patient with platypnoea orthodeoxia with marked shunting through a large
      PFO, evaluated by transesophageal and transthoracic echo.

PMID- 16451831
TI  - Transient total occlusion of the mitral valve orifice by a free-floating left
      atrial ball thrombus.
AB  - In patients with mitral stenosis (MS), a free-floating ball thrombus in the left
      atrium (LA) is a very rare clinical manifestation, but has potentially
      catastrophic consequences such as fatal systemic emboli or total obstruction of
      the narrowed mitral valve orifice, often resulting in sudden death. In this
      report, we demonstrated a free-floating ball thrombus within the LA cavity and
      transient complete occlusion of blood flow through the stenotic mitral valve by
      transthoracic echocardiography. Awareness of the possibility of such an entity,
      early diagnosis and treatment may prevent significant morbidity and mortality.

PMID- 16451830
TI  - Echocardiography of acute mitral prosthesis dehiscence.
AB  - We report a 20-year-old man with acute mitral prosthesis endocarditis complicated
      by valve desinsertion. In developing countries, the lack of surgical facilities
      makes management of these complications difficult.

PMID- 16451833
TI  - Application of microbore HPLC in combination with tandem MS for the
      quantification of rosuvastatin in human plasma.
AB  - The potential of microbore high-performance liquid chromatography (HPLC) in
      combination with tandem mass spectrometry (MS/MS) for the sensitive detection of
      rosuvastatin (Crestor) in human plasma was investigated. Three microbore HPLC
      columns with internal diameters (i.d.) of 0.5, 1.0 and 2.0 mm were evaluated for
      column efficiency and mass sensitivity, and compared to a conventional 4.6 mm
      i.d. column. The 2.0 and 1.0 mm i.d. columns performed very well while the 0.5 mm
      i.d. column was slightly less efficient, this is probably due to a lower packing
      density. Good results with respect to gains in mass sensitivity compared to the
      conventional analytical column were achieved with the 2.0 and 1.0 mm columns.
      Thus, the 2.0 mm i.d. column had an improved signal-to-noise (S/N) ratio of 16
      whilst the 1.0 mm i.d. column had an improved S/N ratio of greater than 70.
      Experiments with the 1.0 mm i.d. HPLC column were performed to determine the
      robustness of the microbore method for human plasma extracts after sample
      preparation using solid-phase extraction (SPE). A number of problems were
      encountered with extracts including high backgrounds, the blocking of the column
      and a rapid deterioration in column performance. The blocking of the column by
      particulates was solved by off-line filtration of the sample extracts. Peak
      tailing of the analytes and high background, both of which were due to endogenous
      interferences in the extracts, were eliminated using gradient elution. Using
      these approaches over 500 injections of plasma extracts were achieved without
      significant deterioration in assay performance. Quantities of rosuvastatin of 0.3
      pg on-column could be detected and cross-validation experiments demonstrated that
      the conventional and the microbore HPLC-MS/MS methods provided similar
      information on the concentration of rosuvastatin but with greatly reduced sample
      consumption using the microbore method.

PMID- 16451832
TI  - The zic1 gene is expressed in chick somites but not in migratory neural crest.
AB  - Zic transcription factors regulate the expression of neural and neural crest
      specific genes and are expressed in the cells of the dorsal neural tube and the
      premigratory neural crest. Here we characterize zic1 expression in the chick
      embryo during somite formation and neural crest migration. zic1 is expressed in
      the dorsomedial portion of epithelial somites and subsequently in the dorsomedial
      lip of the dermomyotome. Although zic1 is expressed in cells of the nascent
      myotome, it is absent from differentiated myotome cells that express myosin. As
      the dorsal root ganglia form, zic1 is expressed at high levels in the dorsal
      sclerotome and zic1 expression is more pronounced in the caudal regions of the
      somites. Double-label experiments showed that cells expressing zic1 are not
      labeled by the HNK-1 antibody specific for migratory neural crest cells. Thus,
      migrating neural crest cells do not express zic1.

PMID- 16451834
TI  - New thinking on neurodevelopment.

PMID- 16451835
TI  - Flu vaccine production gets a shot in the arm.

PMID- 16451837
TI  - Norton Nelson's legacy: the science of environmental health.

PMID- 16451838
TI  - Environmental health sciences and the community.

PMID- 16451839
TI  - Phosphine toxicity: ethical questions.

PMID- 16451840
TI  - Effects of lead on IQ in children.

PMID- 16451841
TI  - Sheep reared on sewage sludge-treated pasture: flawed conclusions.

PMID- 16451842
TI  - Prenatal phthalate exposure and anogenital distance in male infants.

PMID- 16451843
TI  - Phthalates not in plastic food packaging.

PMID- 16451844
TI  - Cloud banks: airlines save halon.

PMID- 16451845
TI  - Making progress on breast cancer.

PMID- 16451846
TI  - Elemental mercury spills.
AB  - Sources of elemental mercury (Hg0) include old natural gas regulators,
      manometers, sphygmomanometers, thermometers, and thermostats. Causes of Hg0
      spills include improper storage, container breakage, children playing with Hg0,
      the breakage of devices containing Hg0, and ritualistic use of Hg0. Inhalation is
      the primary exposure route for Hg0. Mercury released into the environment can
      enter lakes and streams, where bacteria convert it into methylmercury, which
      bioaccumulates in fish. Chronic exposure to Hg0 vapors can damage the kidneys and
      neurologic system. Short-term exposure to high levels of Hg0 vapors may cause
      lung damage, nausea, vomiting, diarrhea, increases in blood pressure or heart
      rate, skin rashes, and eye irritation, among other effects. Minimizing Hg0
      dispersal is important after an Hg0 spill. Tracking by shoes or apparel or
      vacuuming can spread Hg0, increasing airborne concentrations and cleanup costs.
      The Illinois Department of Public Health's response to an Hg0 spill depends on
      the size of the spill. Airborne concentrations after large spills are mapped with
      a mercury vapor analyzer (MVA). The cleanup begins with the spill site and any
      hot spots that were identified with the MVA. Hard surfaces can usually be
      cleaned, but contaminated porous items must be discarded. Leaving marginally
      contaminated items outdoors for a month or more during warm weather may dissipate
      the Hg0. After a cleanup, clearance sampling is conducted to determine if further
      cleanup is needed. The best way to prevent Hg0 spills is reduce its use. Key
      words: cleanup, elemental mercury, health effects, mercury, prevention,
      remediation, spill, spill management.

PMID- 16451847
TI  - Assessing the reliability and credibility of industry science and scientists.
AB  - The chemical industry extensively researches and tests its products to implement
      product stewardship commitments and to ensure compliance with governmental
      requirements. In this commentary we argue that a wide variety of mechanisms
      enable policymakers and the public to assure themselves that studies performed or
      funded by industry are identified as such, meet high scientific standards, and
      are not suppressed when their findings are adverse to industry's interests. The
      more a given study follows these practices and standards, the more confidence one
      can place in it. No federal laws, rules, or policies express a presumption that
      scientific work should be ignored or given lesser weight because of the source of
      its funding. To the contrary, Congress has consistently mandated that agencies
      allow interested or affected parties to provide information to them and fairly
      consider that information. All participants in scientific review panels should
      disclose sources of potential biases and conflicts of interest. The former should
      be considered in seeking a balanced panel rather than being used as a basis for
      disqualification. Conflicts of interest generally do require disqualification,
      except where outweighed by the need for a person's services. Within these
      constraints, chemical industry scientists can serve important and legitimate
      functions on scientific advisory panels and should not be unjustifiably prevented
      from contributing to their work.

PMID- 16451849
TI  - A toxicologic review of quantum dots: toxicity depends on physicochemical and
      environmental factors.
AB  - As a growing applied science, nanotechnology has considerable global
      socioeconomic value, and the benefits afforded by nanoscale materials and
      processes are expected to have significant impacts on almost all industries and
      all areas of society. A diverse array of engineered nanoscale products and
      processes have emerged [e.g., carbon nanotubes, fullerene derivatives, and
      quantum dots (QDs)], with widespread applications in fields such as medicine,
      plastics, energy, electronics, and aerospace. With the nanotechnology economy
      estimated to be valued at dollar 1 trillion by 2012, the prevalence of these
      materials in society will be increasing, as will the likelihood of exposures.
      Importantly, the vastness and novelty of the nanotechnology frontier leave many
      areas unexplored, or underexplored, such as the potential adverse human health
      effects resulting from exposure to novel nanomaterials. It is within this context
      that the need for understanding the potentially harmful side effects of these
      materials becomes clear. The reviewed literature suggests several key points: Not
      all QDs are alike; engineered QDs cannot be considered a uniform group of
      substances. QD absorption, distribution, metabolism, excretion, and toxicity
      depend on multiple factors derived from both inherent physicochemical properties
      and environmental conditions; QD size, charge, concentration, outer coating
      bioactivity (capping material and functional groups), and oxidative, photolytic,
      and mechanical stability have each been implicated as determining factors in QD
      toxicity. Although they offer potentially invaluable societal benefits such as
      drug targeting and in vivo biomedical imaging, QDs may also pose risks to human
      health and the environment under certain conditions. Key words: environment,
      human health, nanomaterials, nanosized particles, nanotechnology, nanotoxicology,
      quantum dots, toxicology.

PMID- 16451848
TI  - Pesticides and Parkinson's disease--is there a link?
AB  - Parkinson's disease (PD) is an idiopathic disease of the nervous system
      characterized by progressive tremor, bradykinesia, rigidity, and postural
      instability. It has been postulated that exogenous toxicants, including
      pesticides, might be involved in the etiology of PD. In this article we present a
      comprehensive review of the published epidemiologic and toxicologic literature
      and critically evaluate whether a relationship exists between pesticide exposure
      and PD. From the epidemiologic literature, there does appear to be a relatively
      consistent relationship between pesticide exposure and PD. This relationship
      appears strongest for exposure to herbicides and insecticides, and after long
      durations of exposure. Toxicologic data suggest that paraquat and rotenone may
      have neurotoxic actions that potentially play a role in the development of PD,
      with limited data for other pesticides. However, both the epidemiology and
      toxicology studies were limited by methodologic weaknesses. Particular issues of
      current and future interest include multiple exposures (both pesticides and other
      exogenous toxicants), developmental exposures, and gene-environment interactions.
      At present, the weight of evidence is sufficient to conclude that a generic
      association between pesticide exposure and PD exists but is insufficient for
      concluding that this is a causal relationship or that such a relationship exists
      for any particular pesticide compound or combined pesticide and other exogenous
      toxicant exposure.

PMID- 16451850
TI  - Blood mercury reporting in NHANES: identifying Asian, Pacific Islander, Native
      American, and multiracial groups.
AB  - INTRODUCTION: Asians, Pacific Islanders, and Native Americans are a potentially
      high-risk group for dietary exposure to methylmercury through fish consumption.
      However, blood mercury levels in this group have not been identified in recent
      reports of the National Health and Nutrition Examination Survey (NHANES) for the
      years 1999-2002. METHODS: We used NHANES data from 1999-2002 to obtain population
      estimates of blood mercury levels among women of childbearing age classified as
      belonging to the "other" racial/ethnic group (Asian, Pacific Islander, Native
      American, and multiracial; n = 140). Blood mercury levels in this group were
      compared with those among all other women participants, classified as Mexican
      American, non-Hispanic black, non-Hispanic white, and "other" Hispanic. RESULTS:
      An estimated 16.59 +/- 4.0% (mean +/- SE) of adult female participants who self
      identified as Asian, Pacific Islander, Native American, or multiracial (n = 140)
      had blood mercury levels > or = 5.8 microg/L, and 27.26 +/- 4.22% had levels > or
      = 3.5 microg/L. Among remaining survey participants (n = 3,497), 5.08 +/- 0.90%
      had blood mercury levels > or = 5.8 microg/L, and 10.86 +/- 1.45% had levels > or
      = 3.5 microg/L. CONCLUSIONS: Study subjects in NHANES who self-identified as
      Asian, Pacific Islander, Native American, or multiracial had a higher prevalence
      of elevated blood mercury than all other racial/ethnic participants in the
      survey. Future studies should address reasons for the high mercury levels in this
      group and explore possible interventions for lowering risk of methylmercury
      exposure in this population.

PMID- 16451851
TI  - Apparent half-lives of hepta- to decabrominated diphenyl ethers in human serum as
      determined in occupationally exposed workers.
AB  - The aim of the present study was to model apparent serum half-lives of
      polybrominated diphenyl ethers (PBDEs) with 7-10 bromine substituents. Workers
      with occupational exposure to PBDEs have elevated serum levels of PBDEs, but
      these substances are also found in the general population and are ubiquitous
      environmental contaminants. The calculations were based on exposure assessments
      of rubber workers (manufactured flame-retarded rubber compound) and electronics
      dismantlers who donated blood during a period with no work-related exposures to
      PBDEs, and referents without any known occupational exposure (clerks, cleaners,
      and abattoir workers). The workers had previously been found to have elevated
      levels of high- and medium-brominated diphenyl ethers compared with the referent
      populations. We performed nonlinear mixed-effects modeling of kinetics, using
      data from previous and present chemical analyses. The calculated apparent half
      life for decabromodiphenyl ether (BDE-209) was 15 days (95% confidence interval,
      11-18 days). The three nona-BDEs and four octa-BDE congeners were found to have
      half-lives of 18-39 and 37-91 days, respectively. BDE-209 has a short half-life
      in human blood. Because BDE-209 is commonly present in humans in general, the
      results of this study imply that humans must be more or less continuously exposed
      to BDE-209 to sustain the serum concentrations observed. BDE-209 is more readily
      transformed and/or eliminated than are lower brominated diphenyl ether congeners,
      and human health risk must be assessed accordingly.

PMID- 16451852
TI  - Dermal exposure to jet fuel JP-8 significantly contributes to the production of
      urinary naphthols in fuel-cell maintenance workers.
AB  - Jet propulsion fuel 8 (JP-8) is the major jet fuel used worldwide and has been
      recognized as a major source of chemical exposure, both inhalation and dermal,
      for fuel-cell maintenance workers. We investigated the contributions of dermal
      and inhalation exposure to JP-8 to the total body dose of U.S. Air Force fuel
      cell maintenance workers using naphthalene as a surrogate for JP-8 exposure.
      Dermal, breathing zone, and exhaled breath measurements of naphthalene were
      obtained using tape-strip sampling, passive monitoring, and glass bulbs,
      respectively. Levels of urinary 1- and 2-naphthols were determined in urine
      samples and used as biomarkers of JP-8 exposure. Multiple linear regression
      analyses were conducted to investigate the relative contributions of dermal and
      inhalation exposure to JP-8, and demographic and work-related covariates, to the
      levels of urinary naphthols. Our results show that both inhalation exposure and
      smoking significantly contributed to urinary 1-naphthol levels. The contribution
      of dermal exposure was significantly associated with levels of urinary 2-naphthol
      but not with urinary 1-naphthol among fuel-cell maintenance workers who wore
      supplied-air respirators. We conclude that dermal exposure to JP-8 significantly
      contributes to the systemic dose and affects the levels of urinary naphthalene
      metabolites. Future work on dermal xenobiotic metabolism and toxicokinetic
      studies are warranted in order to gain additional knowledge on naphthalene
      metabolism in the skin and the contribution to systemic exposure.

PMID- 16451853
TI  - Mortality from ischemic heart disease and diabetes mellitus (type 2) in four U.S.
      wheat-producing states: a hypothesis-generating study.
AB  - In this ecologic study I examined ischemic heart disease (IHD) and diabetes
      mortality in rural agricultural counties of Minnesota, Montana, North Dakota, and
      South Dakota, in association with environmental exposure to chlorophenoxy
      herbicides, using wheat acreage as a surrogate exposure. I collected data on
      agricultural land use and 1979-1998 mortality from the U.S. Department of
      Agriculture and the Centers for Disease Control and Prevention websites,
      respectively. Counties were grouped based on percentage of land area dedicated to
      wheat farming. Poisson relative risks (RR) and 95% confidence intervals (CIs),
      comparing high- and medium- with low-wheat counties, were obtained for IHD, the
      subcategories acute myocardial infarction (AMI) and coronary atherosclerosis
      (CAS), and diabetes, adjusting for sex, age, mortality cohort, and poverty index.
      Mortality from IHD was modestly increased (RR = 1.08; 95% CI, 1.04-1.12).
      Analyses of its two major forms were more revealing. Compared with low-wheat
      counties, mortality in high-wheat counties from AMI increased (RR = 1.20; 95% CI,
      1.14-1.26), and mortality from CAS decreased (RR = 0.89; 95% CI, 0.83-0.96).
      Mortality from AMI was more pronounced for those < 65 years of age (RR = 1.31;
      95% CI 1.22-1.39). Mortality from type 2 diabetes increased (RR = 1.16; 95% CI,
      1.08-1.24). These results suggest that the underlying cause of mortality from AMI
      and type 2 diabetes increased and the underlying cause of mortality from CAS
      decreased in counties where a large proportion of the land area is dedicated to
      spring and durum wheat farming. Firm conclusions on causal inference cannot be
      reached until more definitive studies have been conducted.

PMID- 16451854
TI  - Effects of developmental exposure to 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE
      99) on sex steroids, sexual development, and sexually dimorphic behavior in rats.
AB  - Increasing concentrations of polybrominated flame retardants, including
      polybrominated diphenyl ethers (PBDEs), in breast milk cause concern about
      possible developmental effects in nursed babies. Because previous studies in rats
      have indicated effects on sex steroids and sexually dimorphic behavior after
      maternal exposure to polychlorinated biphenyls (PCBs), our goal in the present
      study was to determine if developmental exposure to 2,2 ,4,4 ,5
      pentabromodiphenyl ether (PBDE-99) induces similar endocrine-mediated effects.
      Pregnant rats were exposed to vehicle or PBDE-99 (1 or 10 mg/kg body weight,
      daily during gestational days 10-18). For comparison, we also included a group
      exposed to the technical PCB mixture Aroclor 1254 (30 mg/kg body weight, daily).
      PBDE exposure resulted in pronounced decreases in circulating sex steroids in
      male offspring at weaning and in adulthood. Female offspring were less affected.
      Anogenital distance was reduced in male offspring. Puberty onset was delayed in
      female offspring at the higher dose level, whereas a slight acceleration was
      detected in low-dose males. The number of primordial/primary ovarian follicles
      was reduced in females at the lower dose, whereas decline of secondary follicles
      was more pronounced at the higher dose. Sweet preference was dose-dependently
      increased in PBDE-exposed adult males, indicating a feminization of this sexually
      dimorphic behavior. Aroclor 1254 did not alter sweet preference and numbers of
      primordial/primary and secondary follicles but it did affect steroid
      concentrations in males and sexual development in both sexes. PBDE concentrations
      in tissues of dams and offspring were highest on gestational day 19. These
      results support the hypothesis that PBDEs are endocrine-active compounds and
      interfere with sexual development and sexually dimorphic behavior.

PMID- 16451855
TI  - Breast milk dioxins in Hong Kong and Pearl River Delta.
AB  - There are no previous reports from South China on chemically determined
      polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans
      (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) in human breast milk
      expressed as World Health Organization (WHO) toxic equivalents (TEQs). In a 2002
      2003 WHO exposure study, 13 pools of breast milk comprising samples from 316
      primiparous women in Hong Kong in 2002 were analyzed by gas chromatography/mass
      spectrometry for 29 PCDD/F and dioxin-like PCB congeners. Total WHO-TEQs ranged
      from 8.97 to 16.7 pg/g fat (weighted mean, 12.9 pg; weighted median, 13.4 pg).
      Variations in TEQs included positive associations with age (R2 = 0.73, p <
      0.0005), higher consumption of dairy products and seafood, and lower TEQs in
      overseas mothers and ever-smokers. Congener profiles indicated geographic
      specificity of exposure in Hong Kong, mainland China, and overseas Asian
      countries, including higher proportions of PCB-TEQs (overseas) and PCDF-TEQs
      (mainland China). The median TEQs of PCDD/Fs (8.69 pg/g fat) and PCBs (4.73 pg/g
      fat) in Hong Kong were highest among the five Asian Pacific countries but lower
      than the levels for at least half of the European countries that participated in
      the WHO study. However, future international studies should incorporate mother's
      age in the design of the pooling strategy to allow standardization by other
      exposure factors and valid comparisons among different countries. The findings
      allow support for the WHO breast-feeding advisory. Trends in human dioxin levels
      in the region cannot yet be determined, and rigorous controls are needed to
      reduce emissions of dioxins and human exposure in mainland China.

PMID- 16451856
TI  - Effects of multiday exposure to ozone on airway inflammation as determined using
      sputum induction.
AB  - Single short-term exposures to ozone are known to cause acute changes in
      pulmonary function and neutrophilic airway inflammation. The respiratory health
      effects of repeated exposures are not as well studied. Pulmonary function
      decrements are known to attenuate, but it is less clear how injury and
      inflammation are affected. Using sputum induction (SI) to sample respiratory
      tract lining fluid after single- and multiday exposures, we designed a study to
      test the hypothesis that neutrophils would increase after multiday exposure
      compared with single-day exposure. In a randomized, crossover design, 15 normal
      healthy subjects were exposed to O3 (0.2 ppm) under two conditions: for 4 hr for
      1 day (1D) and for 4 hr for 4 consecutive days (4D). Pulmonary function testing
      was performed immediately before and after each 4-hr exposure. The SI was
      performed 18 hr after the end of the 1D and 4D conditions. The symptom and
      pulmonary function data followed a pattern seen in other multiday O3 exposure
      studies, with the greatest changes occurring on the second day. In contrast to
      previous studies using bronchoalveolar lavage, however, there was a significant
      increase in the percentage of neutrophils and a significant decrease in the
      percentage of macrophages after the 4D condition compared with the 1D condition.
      Given that SI likely samples proximal airways better than distal lung, these
      results add to the body of evidence that differential airway compartmental
      responses to O3 occur in humans and other species.

PMID- 16451857
TI  - Cancer in persons working in dry cleaning in the Nordic countries.
AB  - U.S. studies have reported an increased risk of esophageal and some other cancers
      in dry cleaners exposed to tetrachloroethylene. We investigated whether the U.S.
      findings could be reproduced in the Nordic countries using a series of case
      control studies nested in cohorts of laundry and dry-cleaning workers identified
      from the 1970 censuses in Denmark, Norway, Sweden, and Finland. Dry-cleaning work
      in the Nordic countries during the period when tetrachloroethylene was the
      dominant solvent was not associated with an increased risk of esophageal cancer
      [rate ratio (RR) = 0.76; 95% confidence interval (CI), 0.34-1.69], but our study
      was hampered by some unclassifiable cases. The risks of cancer of the gastric
      cardia, liver, pancreas, and kidney and non-Hodgkin lymphoma were not
      significantly increased. Assistants in dry-cleaning shops had a borderline
      significant excess risk of cervical cancer not found in women directly involved
      in dry cleaning. We found an excess risk of bladder cancer (RR = 1.44; 95% CI,
      1.07-1.93) not associated with length of employment. The finding of no excess
      risk of esophageal cancer in Nordic dry cleaners differs from U.S. findings.
      Chance, differences in level of exposure to tetrachloroethylene, and confounding
      may explain the findings. The overall evidence on bladder cancer in dry cleaners
      is equivocal.

PMID- 16451858
TI  - Assessing the measurement precision of various arsenic forms and arsenic exposure
      in the National Human Exposure Assessment Survey (NHEXAS).
AB  - Archived samples collected from 1995 to 1997 in the National Human Exposure
      Assessment Survey (NHEXAS) in U.S. Environmental Protection Agency Region 5 (R5)
      and the Children's Study (CS) in Minnesota were analyzed for total arsenic,
      arsenate [As(V)], arsenite, dimethyl arsenic acid (DMA), monomethyl arsenic acid
      (MMA), arsenobetaine (AsB), and arsenocholine. Samples for the CS included
      drinking water, urine, hair, and dust; both studies included food (duplicate
      plate, composited 4-day food samples from participants). Except for AsB and
      As(V), the levels for As species measured in the food and drinking water samples
      were very low or nonexistent. The analytical methods used for measuring As
      species were sensitive to < 1 ppb. During the analysis of food and drinking water
      samples, chromatographic peaks appeared that contained As, but they did not
      correspond to those being quantified. Thus, in some samples, the sum of the
      individual As species levels was less than the total As level measured because
      the unknown forms of As were not quantified. On the other hand, total As was
      detectable in almost all samples (> 90%) except for hair (47%), indicating that
      the analytical method was sufficiently sensitive. Population distributions of As
      concentrations measured in drinking water, food (duplicate plate), dust, urine,
      and hair were estimated. Exposures to total As in food for children in the CS
      were about twice as high as in the general R5 population (medians of 17.5 ppb and
      7.72 ppb, respectively). In addition, AsB was the most frequently detected form
      of As in food eaten by the participants, while As(V) was only rarely detected.
      Thus, the predominant dietary exposure was from an organic form of As. The major
      form of As in drinking water was As(V). Spearman (rank) correlations and Pearson
      (log-concentration scale) correlations between the biomarkers (urine, hair) and
      the other measures (food, drinking water, dust) and urine versus hair were
      performed. In the NHEXAS CS, total As and AsB in the food eaten were
      significantly correlated with their levels in urine. Also, levels of As(V) in
      drinking water correlated with DMA and MMA in urine. Arsenic levels in dust did
      not show a relationship with urine or hair levels, and no relationship was
      observed for food, drinking water, and dust with hair. Urine samples were
      collected on days 3, 5, and 7 of participants' monitoring periods. Total As
      levels in urine were significantly associated across the three pairwise
      combinations--i.e., day 3 versus day 5, day 3 versus day 7, and day 5 versus day
      7. Because the half-life of As in the body is approximately 3 days, this suggests
      that some exposure occurred continually from day to day. This trend was also
      observed for AsB, suggesting that food is primarily responsible for the continual
      exposure. DMA and MMA in urine were also significantly correlated but not in all
      combinations.

PMID- 16451859
TI  - A randomized controlled trial assessing infectious disease risks from bathing in
      fresh recreational waters in relation to the concentration of Escherichia coli,
      intestinal enterococci, Clostridium perfringens, and somatic coliphages.
AB  - We performed epidemiologic studies at public freshwater bathing sites in Germany
      to provide a better scientific basis for the definition of recreational water
      quality standards. A total of 2,196 participants were recruited from the local
      population and randomized into bathers and nonbathers. Bathers were exposed for
      10 min and had to immerse their head at least three times. Water samples for
      microbiological analysis were collected at 20-min intervals. Unbiased
      concentration-response effects with no-observed-adverse-effect levels (NOAELs)
      were demonstrated for three different definitions of gastroenteritis and four
      fecal indicator organisms. Relative risks for bathing in waters with levels above
      NOAELs compared with nonbathing ranged from 1.8 (95% CI, 1.2-2.6) to 4.6 (95% CI,
      2.1-10.1), depending on the definition of gastroenteritis. The effect of
      swallowing water provided additional evidence for true dose-response
      relationships. Based on the NOAELs, the following guide values for water quality
      are suggested: 100 Escherichia coli, 25 intestinal enterococci, 10 somatic
      coliphages, or 10 Clostridium perfringens per 100 mL. Recreational water quality
      standards are intended to protect the health of those consumers who are not
      already immune or resistant to pathogens that may be associated with indicator
      organisms. In contrast to current World Health Organization recommendations, we
      concluded that standards should be based on rates of compliance with NOAELs
      rather than on attributable risks determined above NOAELs, because these risks
      depend mainly on the unpredictable susceptibility of the cohorts. Although in
      theory there is no threshold in real concentration-response relationships, we
      demonstrated that a NOAEL approach would be a more robust and practical solution
      to the complex problem of setting standards.

PMID- 16451860
TI  - Exposure to fumonisins and the occurrence of neural tube defects along the Texas
      Mexico border.
AB  - Along the Texas-Mexico border, the prevalence of neural tube defects (NTDs) among
      Mexican-American women doubled during 1990-1991. The human outbreak began during
      the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin
      that often contaminates corn. Because Mexican Americans in Texas consume large
      quantities of corn, primarily in the form of tortillas, they may be exposed to
      high levels of fumonisins. We examined whether or not maternal exposure to
      fumonisins increases the risk of NTDs in offspring using a population-based case
      control study. We estimated fumonisin exposure from a postpartum
      sphinganine:sphingosine (sa:so) ratio, a biomarker for fumonisin exposure
      measured in maternal serum, and from maternal recall of periconceptional corn
      tortilla intake. After adjusting for confounders, moderate (301-400) compared
      with low (< or = 100) consumption of tortillas during the first trimester was
      associated with increased odds ratios (ORs) of having an NTD-affected pregnancy
      (OR = 2.4; 95% confidence interval, 1.1-5.3). No increased risks were observed at
      intakes higher than 400 tortillas (OR = 0.8 for 401-800, OR = 1.0 for > 800).
      Based on the postpartum sa:so ratio, increasing levels of fumonisin exposure were
      associated with increasing ORs for NTD occurrences, except for the highest
      exposure category (sa:so > 0.35). Our findings suggest that fumonisin exposure
      increases the risk of NTD, proportionate to dose, up to a threshold level, at
      which point fetal death may be more likely to occur. These results also call for
      population studies that can more directly measure individual fumonisin intakes
      and assess effects on the developing embryo.

PMID- 16451861
TI  - Survival analysis to estimate association between short-term mortality and air
      pollution.
AB  - BACKGROUND: Ecologic studies are commonly used to report associations between
      short-term air pollution and mortality. In such studies, the unit of observation
      is the day rather than the individual. Moreover, individual data on the subjects
      are rarely available, which limits the assessment of individual risk factors.
      These associations can also be investigated using case-crossover studies.
      However, by definition, individual risk factors are not studied, and such studies
      analyze only dead subjects, which limits the statistical power. OBJECTIVE: We
      suggest that the survival analysis is more suitable when cohorts are examined
      with a time-dependent ecologic exposure. To our knowledge, to date this type of
      analysis has never been proposed. DESIGN, PARTICIPANTS, MEASUREMENTS: In the
      present study we used a Cox proportional hazards model to investigate the
      distribution over time of the short-term effect of black smoke and sulfur dioxide
      in 439 nonaccidental and 158 cardiorespiratory deaths among the 1,469 subjects of
      the Personnes Agees QUID (PAQUID) cohort in Bordeaux, France. The model has a
      delayed entry and a polynomial distributed lag from 0 to 5 days. Results are
      adjusted for individual risk factors, temperature, relative humidity, weekday,
      season, influenza epidemics, and a time function to control temporal trends.
      RESULTS: We identified a positive and significant association between
      cardiorespiratory mortality and black smoke, with a 24% increase in deaths 3 days
      after a 10-microg/m3 increase in black smoke (95% confidence interval, 4-47%).
      CONCLUSIONS: We conclude that the Cox proportional hazards model with time
      dependent covariates is very suitable to investigate simultaneously the short
      term effect of air pollution on health and the effect of individual risk factors
      on a cohort study.

PMID- 16451862
TI  - Radio frequency nonionizing radiation in a community exposed to radio and
      television broadcasting.
AB  - Exposure to radio frequency (RF) nonionizing radiation from telecommunications is
      pervasive in modern society. Elevated disease risks have been observed in some
      populations exposed to radio and television transmissions, although findings are
      inconsistent. This study quantified RF exposures among 280 residents living near
      the broadcasting transmitters for Denver, Colorado. RF power densities outside
      and inside each residence were obtained, and a global positioning system (GPS)
      identified geographic coordinates and elevations. A view-shed model within a
      geographic information system (GIS) characterized the average distance and
      percentage of transmitters visible from each residence. Data were collected at
      the beginning and end of a 2.5-day period, and some measurements were repeated 8
      29 months later. RF levels logged at 1-min intervals for 2.5 days varied
      considerably among some homes and were quite similar among others. The greatest
      differences appeared among homes within 1 km of the transmitters. Overall, there
      were no differences in mean residential RF levels compared over 2.5 days.
      However, after a 1- to 2-year follow-up, only 25% of exterior and 38% of interior
      RF measurements were unchanged. Increasing proximity, elevation, and line-of
      sight visibility were each associated with elevated RF exposures. At average
      distances from > 1-3 km, exterior RF measurements were 13-30 times greater among
      homes that had > 50% of the transmitters visible compared with homes with < or =
      50% visibility at those distances. This study demonstrated that both spatial and
      temporal factors contribute to residential RF exposure and that GPS/GIS
      technologies can improve RF exposure assessment and reduce exposure
      misclassification.

PMID- 16451864
TI  - Organic diets significantly lower children's dietary exposure to organophosphorus
      pesticides.
AB  - We used a novel study design to measure dietary organophosphorus pesticide
      exposure in a group of 23 elementary school-age children through urinary
      biomonitoring. We substituted most of children's conventional diets with organic
      food items for 5 consecutive days and collected two spot daily urine samples,
      first-morning and before-bedtime voids, throughout the 15-day study period. We
      found that the median urinary concentrations of the specific metabolites for
      malathion and chlorpyrifos decreased to the nondetect levels immediately after
      the introduction of organic diets and remained nondetectable until the
      conventional diets were reintroduced. The median concentrations for other
      organophosphorus pesticide metabolites were also lower in the organic diet
      consumption days; however, the detection of those metabolites was not frequent
      enough to show any statistical significance. In conclusion, we were able to
      demonstrate that an organic diet provides a dramatic and immediate protective
      effect against exposures to organophosphorus pesticides that are commonly used in
      agricultural production. We also concluded that these children were most likely
      exposed to these organophosphorus pesticides exclusively through their diet. To
      our knowledge, this is the first study to employ a longitudinal design with a
      dietary intervention to assess children's exposure to pesticides. It provides new
      and persuasive evidence of the effectiveness of this intervention.

PMID- 16451863
TI  - Proteomic evaluation of neonatal exposure to 2,2 ,4,4 ,5-pentabromodiphenyl
      ether.
AB  - Exposure to the brominated flame retardant 2,2 ,4,4 ,5-pentabromodiphenyl ether
      (PBDE-99) during the brain growth spurt disrupts normal brain development in mice
      and results in disturbed spontaneous behavior in adulthood. The
      neurodevelopmental toxicity of PBDE-99 has been reported to affect the
      cholinergic and catecholaminergic systems. In this study we use a proteomics
      approach to study the early effect of PBDE-99 in two distinct regions of the
      neonatal mouse brain, the striatum and the hippocampus. A single oral dose of
      PBDE-99 (12 mg/kg body weight) or vehicle was administered to male NMRI mice on
      neonatal day 10, and the striatum and the hippocampus were isolated. Using two
      dimensional fluorescence difference gel electrophoresis (2D-DIGE), we found 40
      and 56 protein spots with significantly (p < 0.01) altered levels in the striatum
      and the hippocampus, respectively. We used matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-ToF-MS) to determine the
      protein identity of 11 spots from the striatum and 10 from the hippocampus. We
      found that the levels of proteins involved in neurodegeneration and
      neuroplasticity (e.g., Gap-43/neuromodulin, stathmin) were typically altered in
      the striatum, and proteins involved in metabolism and energy production [e.g.,
      alpha-enolase; gamma-enolase; ATP synthase, H+ transporting, mitochondrial F1
      complex, beta subunit (Atp5b); and alpha-synuclein] were typically altered in the
      hippocampus. Interestingly, many of the identified proteins have been linked to
      protein kinase C signaling. In conclusion, we identify responses to early
      exposure to PBDE-99 that could contribute to persistent neurotoxic effects. This
      study also shows the usefulness of proteomics to identify potential biomarkers of
      developmental neurotoxicity of organohalogen compounds.

PMID- 16451865
TI  - Measuring potential dermal transfer of a pesticide to children in a child care
      center.
AB  - Currently, the major determinants of children's exposure to pesticides are not
      fully understood, and approaches for measuring and assessing dermal exposure in a
      residential setting have not been sufficiently evaluated. In one approach, dermal
      exposure is estimated using empirically derived transfer coefficients. To assess
      the feasibility of using this approach for assessing children's exposure to
      pesticides, we conducted a study was conducted in a child care center that had a
      preexisting contract with a pest control service for regular monthly pesticide
      applications. Children in the selected child care center were monitored using
      full-body cotton garments to measure dermal loading. Pesticide residues on
      classroom surfaces were measured in the areas where the children spent time.
      Measured surface-wipe loadings ranged from 0.47 to 120 ng/cm2, and total garment
      loadings ranged from 0.5 to 660 pg/cm2. The garment and surface loading
      measurements were used to calculate dermal-transfer coefficients for use in
      assessing children's residential exposure to pesticides. Dermal-transfer
      coefficients calculated using these data range from approximately 10 to 6,000
      cm2/hr. The wide range in these values demonstrates the importance of developing
      standard surface-measurement protocols if this approach is to be used to assess
      dermal exposure in a residential environment. The upper-range values resulting
      from this study were found to be similar to the default value used by the U.S.
      Environmental Protection Agency to assess children's dermal exposures resulting
      from contact with indoor surfaces.

PMID- 16451866
TI  - Human breast milk contamination with phthalates and alterations of endogenous
      reproductive hormones in infants three months of age.
AB  - Phthalates adversely affect the male reproductive system in animals. We
      investigated whether phthalate monoester contamination of human breast milk had
      any influence on the postnatal surge of reproductive hormones in newborn boys as
      a sign of testicular dysgenesis. DESIGN: We obtained biologic samples from a
      prospective Danish-Finnish cohort study on cryptorchidism from 1997 to 2001. We
      analyzed individual breast milk samples collected as additive aliquots 1-3 months
      postnatally (n = 130; 62 cryptorchid/68 healthy boys) for phthalate monoesters
      [mono-methyl phthalate (mMP), mono-ethyl phthalate (mEP), mono-n-butyl phthalate
      (mBP), mono-benzyl phthalate (mBzP), mono-2-ethylhexyl phthalate (mEHP), mono
      isononyl phthalate (miNP)]. We analyzed serum samples (obtained in 74% of all
      boys) for gonadotropins, sex-hormone binding globulin (SHBG), testosterone, and
      inhibin B. RESULTS: All phthalate monoesters were found in breast milk with large
      variations [medians (minimum-maximum)]: mMP 0.10 (< 0.01-5.53 microg/L), mEP 0.95
      (0.07-41.4 microg/L), mBP 9.6 (0.6-10,900 microg/L), mBzP 1.2 (0.2-26 microg/L),
      mEHP 11 (1.5-1,410 microg/L), miNP 95 (27-469 microg/L). Finnish breast milk had
      higher concentrations of mBP, mBzP, mEHP, and Danish breast milk had higher
      values for miNP (p = 0.0001-0.056). No association was found between phthalate
      monoester levels and cryptorchidism. However, mEP and mBP showed positive
      correlations with SHBG (r = 0.323, p = 0.002 and r = 0.272, p = 0.01,
      respectively); mMP, mEP, and mBP with LH:free testosterone ratio (r = 0.21-0.323,
      p = 0.002-0.044) and miNP with luteinizing hormone (r = 0.243, p = 0.019). mBP
      was negatively correlated with free testosterone (r = -0.22, p = 0.033). Other
      phthalate monoesters showed similar but nonsignificant tendencies. CONCLUSIONS:
      Our data on reproductive hormone profiles and phthalate exposures in newborn boys
      are in accordance with rodent data and suggest that human Leydig cell development
      and function may also be vulnerable to perinatal exposure to some phthalates. Our
      findings are also in line with other recent human data showing incomplete
      virilization in infant boys exposed to phthalates prenatally.

PMID- 16451867
TI  - A case-crossover study of wintertime ambient air pollution and infant
      bronchiolitis.
AB  - We examined the association of infant bronchiolitis with acute exposure to
      ambient air pollutants. DESIGN: We employed a time-stratified case-crossover
      method and based the exposure windows on a priori, biologically based hypotheses.
      PARTICIPANTS: We evaluated effects in 19,901 infants in the South Coast Air Basin
      of California in 1995-2000 with a hospital discharge record for bronchiolitis in
      the first year of life (International Classification of Diseases, 9th Revision,
      CM466.1). EVALUATIONS/MEASUREMENTS: Study subjects' ZIP code was linked to
      ambient air pollution monitors to derive exposures. We estimated the risk of
      bronchiolitis hospitalization associated with increases in wintertime ambient air
      pollutants using conditional logistic regression. RESULTS: We observed no
      increased risk after acute exposure to particulate matter < or = 2.5 microm in
      aerodynamic diameter (PM2.5), carbon monoxide, or nitrogen dioxide. PM2.5
      exposure models suggested a 26-41% increased risk in the most premature infants
      born at gestational ages between 25 and 29 weeks; however, these findings were
      based on very small numbers. CONCLUSIONS: We found little support for a link
      between acute increases in ambient air pollution and infant bronchiolitis except
      modestly increased risk for PM2.5 exposure among infants born very prematurely.
      In these infants, the periods of viral acquisition and incubation concurred with
      the time of increased risk. RELEVANCE TO PROFESSIONAL PRACTICE: We present novel
      data for the infant period and the key respiratory disease of infancy,
      bronchiolitis. Incompletely explained trends in rising bronchiolitis
      hospitalization rates and increasing number of infants born prematurely
      underscore the importance of evaluating the impact of ambient air pollution in
      this age group in other populations and studies.

PMID- 16451868
TI  - The influence of large-scale airborne particle decline and traffic-related
      exposure on children's lung function.
AB  - Between 1991 and 2000, ambient air pollution in East Germany changed to resemble
      West German pollution levels: The concentration of total suspended particles
      (TSPs) decreased on a broad scale while traffic increased. During that time, we
      analyzed total lung capacity (TLC) and airway resistance (R(aw)) of East and West
      German children. We tested children 5-7 years of age (n = 2,574) with cooperation
      independent body plethysmography in repeated cross sections. We used random
      effect models to determine the mutually adjusted association between lung
      function and short-term and chronic particle exposure and its interaction with
      living near a busy road. Annual averages of TSPs declined from 77 to 44
      microg/m2; averages on the day of investigation declined from 133 to 30
      microg/m2. Differences in lung function between East and West German children
      vanished during the investigation time. The association of TSPs with R(aw) and
      TLC was stronger in children living > 50 m away from busy roads. East German
      children from this group had an R(aw) 2.5% higher [95% confidence interval (CI),
      0.0-5.1%] per 40-microg/m2 increase of daily TSP averages. TLC decreased by 6.2%
      (95% CI, 0.04-11.6%) per 40-microg/m2 increase in annual mean TSPs, and this
      effect was equally pronounced in East and West Germany. TSP exposure decreased on
      a broad scale between 1991 and 2000. Lower concentrations of TSPs were associated
      with better measures of lung function in 6-year-old children. For children living
      near busy roads, this effect was diminished.

PMID- 16451869
TI  - Preface: recent findings in mercury health effects.

PMID- 16451870
TI  - Personality traits in miners with past occupational elemental mercury exposure.
AB  - In this study, we evaluated the impact of long-term occupational exposure to
      elemental mercury vapor (Hg0) on the personality traits of ex-mercury miners.
      Study groups included 53 ex-miners previously exposed to Hg0 and 53 age-matched
      controls. Miners and controls completed the self-reporting Eysenck Personality
      Questionnaire and the Emotional States Questionnaire. The relationship between
      the indices of past occupational exposure and the observed personality traits was
      evaluated using Pearson's correlation coefficient and on a subgroup level by
      machine learning methods (regression trees). The ex-mercury miners were
      intermittently exposed to Hg0 for a period of 7-31 years. The means of exposure
      cycle urine mercury (U-Hg) concentrations ranged from 20 to 120 microg/L. The
      results obtained indicate that ex-miners tend to be more introverted and sincere,
      more depressive, more rigid in expressing their emotions and are likely to have
      more negative self-concepts than controls, but no correlations were found with
      the indices of past occupational exposure. Despite certain limitations, results
      obtained by the regression tree suggest that higher alcohol consumption per se
      and long-term intermittent, moderate exposure to Hg0 (exposure cycle mean U-Hg
      concentrations > 38.7 < 53.5 microg/L) in interaction with alcohol remain a
      plausible explanation for the depression associated with negative self-concept
      found in subgroups of ex-mercury miners. This could be one of the reason for the
      higher risk of suicide among miners of the Idrija Mercury Mine in the last 45
      years.

PMID- 16451871
TI  - The roles of serum selenium and selenoproteins on mercury toxicity in
      environmental and occupational exposure.
AB  - Many studies have found that mercury (Hg) exposure is associated with selenium
      (Se) accumulation in vivo. However, human studies are limited. To study the
      interaction between Se and Hg, we investigated the total Se and Hg concentrations
      in body fluids and serum Se-containing proteins in individuals exposed to high
      concentrations of Hg. Our objective was to elucidate the possible roles of serum
      Se and selenoproteins in transporting and binding Hg in human populations. We
      collected data from 72 subjects: 35 had very low Hg exposure as evidenced by mean
      Hg concentrations of 0.91 and 1.25 ng/mL measured in serum and urine,
      respectively; 37 had high exposure (mean Hg concentrations of 38.5 and 86.8 ng/mL
      measured in serum and urine, respectively). An association between Se and Hg was
      found in urine (r = 0.625; p < 0.001) but not in serum. Hg exposure may affect Se
      concentrations and selenoprotein distribution in human serum. Expression of both
      selenoprotein P and glutathione peroxidase (GSH-Px) was greatly increased in Hg
      miners. These increases were accompanied by elevated Se concentrations in serum.
      In addition, selenoprotein P bound more Hg at higher Hg exposure concentrations.
      Biochemical observations revealed that both GSH-Px activity and malondialdehyde
      concentrations increased in serum of the Hg-exposed group. This study aids in the
      understanding of the interaction between Se and Hg. Selenoproteins play two
      important roles in protecting against Hg toxicity. First, they may bind more Hg
      through their highly reactive selenol group, and second, their antioxidative
      properties help eliminate the reactive oxygen species induced by Hg in vivo.

PMID- 16451872
TI  - New evidence on variations of human body burden of methylmercury from fish
      consumption.
AB  - Epidemiologic studies commonly use mercury (Hg) level in hair as a valid proxy to
      estimate human exposure to methylmercury (MeHg) through fish consumption. This
      study presents the results yielded by a complete data set on fish consumption
      habits, Hg levels in edible fish resources, and corresponding Hg accumulation in
      hair, gathered in three distinct communities of eastern Canada. For one of these
      communities, the average hair Hg concentration was 14 times less than the
      expected value based on calculated daily oral exposure and current knowledge of
      MeHg metabolism. This finding could be explained by differences in specific
      genetic characteristics and/or interactive effects of other dietary components.

PMID- 16451874
TI  - What's 'in the body' is actually 'in the mind'!

PMID- 16451873
TI  - Prenatal methylmercury exposure and developmental outcomes: review of the
      evidence and discussion of future directions.
AB  - I conducted a review of the published literature to assess the strength of the
      evidence for an association between prenatal exposure to methylmercury (MeHg) and
      subsequent child development. I identified 12 studies on this subject published
      since 1980. Of these, 3 were longitudinal studies--2 conducted in the Seychelle
      Islands, and 1 in the Faroe Islands. Nine were cross-sectional studies conducted
      in different countries where seafood, a source of MeHg, constituted a major part
      of the diet. The ages of the children studied ranged from 2 weeks to 12 years.
      The results of the longitudinal studies were contradictory. Researchers in the
      Faroe Islands identified an association between MeHg exposure and developmental
      effects, whereas those in the Seychelle Islands identified no such association.
      This inconsistency was mirrored in the results of the cross-sectional studies
      where there were some positive and some negative findings. It was concluded that
      it was not possible from currently available data to determine whether there is
      an association between prenatal MeHg exposure and adverse developmental effects
      in children. In advance of future research, consideration should be given to
      resolving the uncertainties surrounding exposure assessment and outcome
      measurement, as both elements varied between studies. It was suggested that
      questions of exposure assessment would benefit from the application of an expert
      review process. Outcome assessment would benefit from the development of
      theoretically based measures of specific aspects of cognitive functioning to
      replace the relatively crude measures of attainment and IQ currently employed in
      most studies. This would assist in the development of classic longitudinal
      studies by allowing repeated assessment over the full age range and providing
      data that are more readily interpretable and comparable between studies.

PMID- 16451875
TI  - Towards better understanding and management of somatoform disorders.
AB  - Much research has recently been conducted on somatoform disorders demonstrating
      their clinical importance, associated health-service burden and economic cost.
      These conditions are often comorbid with other mental and physical disorders and
      particularly prevalent in primary care and general medical settings. Although
      culture-specific manifestations and variations of somatization occur--it is now
      accepted that medically unexplained somatic symptoms are a universal phenomenon.
      The management of somatoform disorders is generally a complex and lengthy
      process; however, a number of recent studies have demonstrated the effectiveness
      of short-term treatments such as cognitive behaviour therapy and educational
      interventions. Despite advances in their understanding and treatment, debate
      still surrounds the conceptualization and categorization of somatoform disorders,
      with a number of experts proposing a complete re-evaluation and reassignment of
      this diagnostic classification category. The following paper represents a review
      of recently published literature on frequency, characteristics,
      conceptualization, impact and management of somatoform disorders.

PMID- 16451876
TI  - Somatoform disorders as disorders of affect regulation: a development
      perspective.
AB  - This paper considers the role of disturbances in affect regulation in the
      development and course of somatoform disorders. We first give an overview of
      contemporary theories in the field of psychosomatic medicine that links deficits
      in emotion regulation to the process of somatization, and then review recent
      empirical research that focuses on the association between affect regulation and
      somatoform disorders, with an emphasis on studies investigating the alexithymia
      construct. Overall, the findings suggest that somatoform disorders are linked to
      a diminished capacity to consciously experience and differentiate affects and
      express them in an adequate or healthy way. It must be noted, however, that this
      result has not been obtained exclusively for somatoform disorders. A promising
      approach to further our understanding of the developmental roots of impaired
      affect regulation in somatoform disorders is attachment research. The attachment
      research reviewed in this paper indicates that a dismissing status of attachment
      is linked to defensive forms of processing and expressing emotions. We present
      some new data that not only provide empirical support of a high proportion of
      dismissing attachment in somatoform disorders but also suggest that the degree to
      which somatoform disorder patients employ dismissing attachment strategies is
      strongly related to affect dysregulation. Finally, some implications for
      psychotherapeutic interventions in patients with somatoform disorders are
      considered.

PMID- 16451877
TI  - Somatization, somatosensory amplification, attribution styles and illness
      behaviour: a review.
AB  - Somatic symptoms have been conceptualized in many different ways in literature.
      Current classifications mainly focus on the numbers of symptoms, with relative
      neglect of the underlying psychopathology. Researchers have emphasized the
      importance of a number of experiential, perceptual and cognitive-behavioural
      aspects of somatization. This review focuses on existing literature on the role
      of somatosensory amplification, attribution styles, and illness behaviour in
      somatization. Evidence suggests that somatosensory amplification is neither
      sensitive nor specific to somatizing states, and that other factors like anxiety,
      depression, neuroticism, alexithymia may also have an influence. Attribution
      research supports the existence of multiple causal attributions, which are
      related to the numbers of somatic symptoms. While somatizing patients have more
      organic attributions, depressed patients have more psychological attributions. A
      global somatic attribution style is associated with the number of obscure somatic
      symptoms, while a psychological attribution style is associated with both-
      psychological and somatic-- symptoms of depression and anxiety. There are
      conflicting findings with respect to the role of normalizing attributions in
      reducing physician recognition of anxiety and depression. Specific symptom
      attributions appear to explain physician recognition of psychological distress,
      but global attribution styles do not appear to explain any further variance in
      physician recognition beyond that explained by specific causal attributions.
      Illness behaviour has been studied in two distinct ways in literature. Research
      focusing on attendance rates as a form of illness behaviour suggests that
      somatization is associated with high levels of health care utilization. There is
      also some evidence that health care utilization, amplification and attributions
      styles may be interrelated among somatizing patients. More structured ways to
      assess illness behaviour have found high levels of abnormal illness behaviour in
      this population. Overall, research appears to suggest a complex (and as yet
      unclear) relationship between somatic symptoms and underlying cognitions/illness
      behaviours. While it is clear that somatization is closely related to a number of
      perceptual and cognitive-behavioural factors, the precise nature of these
      relationships are yet to be elucidated.

PMID- 16451878
TI  - Somatoform disorders in the workplace in Japan.
AB  - The literature related to somatoform disorders in the workplace is very limited,
      and these disorders need more attention from mental health professionals in the
      workplace as well as from employers. Over the last decade, major changes have
      taken place in the work environment in Japan. More stress and less support from
      supervisors or colleagues in the workplace have made employees stressed out. The
      number of employees with mental disorders, including somatoform disorders, taking
      sick leave has significantly increased. In our multi-centre collaborative study,
      somatoform disorders were the third most prevalent psychiatric disorder in
      employees, after mood and schizophrenic disorders. Employees with neurotic
      disorders manifested physical symptoms more frequently than those without. Young
      employees frequently reported somatic symptoms such as general malaise, nausea,
      constipation, diarrhoea, headache, stiff shoulder, and dizziness. A rational new
      approach is needed to tackle this important psychopathology increasingly seen
      among employees.

PMID- 16451879
TI  - Somatization disorders in dermatology.
AB  - This paper reviews a wide range of somatization-related symptoms that are
      encountered in dermatology. These include the unexplained cutaneous sensory
      syndromes especially the cutaneous dysesthesias associated with pain, numbness
      and pruritus; traumatic memories in post-traumatic stress disorder (PTSD) which
      are experienced on a sensory level as 'body memories' and may present as local or
      generalized pruritic states, urticaria and angioedema; and unexplained flushing
      reactions and profuse perspiration, in addition to unexplained exacerbations of
      stress-reactive dermatoses such as psoriasis and atopic eczema secondary to the
      autonomic hyperarousal in PTSD; classic 'pseudoneurologic' symptoms associated
      with dissociation including unexplained loss of touch or pain, in addition to the
      self-induced dermatoses such as dermatitis artefacta and trichotillomania that
      are encountered with dissociative states; and body dysmorphic disorder where the
      patient often presents with a somatic preoccupation involving the skin or hair.

PMID- 16451880
TI  - Somatization in cancer.
AB  - Somatic symptoms can occur in disease-free cancer patients. The causes of such
      symptoms in cancer can be many and varied. These could be due to anxiety,
      depression, somatization or a manifestation of illness behaviour. Somatic
      symptoms can also arise out of treatments for the cancer like radiation treatment
      or chemotherapy. Cancer related somatic symptoms have cognitive, psychological,
      and physiological causes, each of which is amenable to treatment. The occurrence
      of somatoform disorders in cancer patients is likely to complicate the treatment
      and outcome of the cancer. Common somatic symptoms in cancer have been found to
      be pain, fatigue, anorexia, tiredness or exhaustion, weakness, reduced energy,
      lethargy, and tremors. Breathlessness, muscle pain, dizziness, and palpitation
      are common symptoms of anxiety and panic attack which have also been noted in
      cancer patients. Somatic concern and preoccupation are also common. These
      symptoms create difficulty in diagnosing depression and anxiety in cancer
      patients, and leads to the need for modification of the standard diagnostic
      criteria. Somatic symptoms in cancer respond to counselling and
      psychopharmacotherapy. More research are needed on this area to understand the
      process of somatization in a somatic disease.

PMID- 16451881
TI  - Somatoform disorders: perspectives from Pakistan.
AB  - Somatoform disorders represent widespread and largely unsolved problems at the
      border between psychiatry and medicine. Patients with somatoform disorders often
      present difficult diagnostic and management problems. A series of three community
      based epidemiological surveys of rural and urban populations in Pakistan found
      high prevalence of common mental disorders where the core presentations were
      somatic complaints. All the three epidemiological surveys used the Bradford
      Somatic Inventory (BSI), which was developed from symptom reports by psychiatric
      patients in Pakistan; these enquired about somatic symptoms in the local
      language, taking into account local cultural idioms of distress. At a
      conservative estimate, 66% of women and 25% men suffered from anxiety and
      depressive disorders whereby the complaints predominantly were somatic in nature.
      People in rural non-Western cultures are not psychologically minded and do not
      have abstract language or concepts of emotional distress and therefore
      communicate their emotions somatically. In Pakistan somatoform disorders possess
      a prominent diagnostic dilemma. The cornerstone of the management is a
      comprehensive medical, psychiatric and psychosocial evaluation of the patient.
      Patients with multiple somatic complaints not only present formidable management
      problems but also often have severe functional impairments that may outweigh
      those of patients with other so-called severe mental illnesses. Since somatoform
      disorders are the most common psychiatric disorders to present in non-psychiatric
      settings, it is important that training about them begin at undergraduate level.
      It should also be incorporated in the training of a wide variety of non
      psychiatric specialists, both medical and non-medical.

PMID- 16451882
TI  - Somatoform disorders: the role of consultation liaison psychiatry.
AB  - The somatoform disorders are encountered commonly in both primary and secondary
      care. Despite their high incidence, few hospitals have teams with the expertise
      to manage this group of conditions. The lack of appropriate carers leads to
      inappropriate care, including increased numbers of admissions and investigations,
      to the detriment of the patients. The absence of appropriate care also increases
      the cost to the health services. Multidisciplinary Consultation Liaison (C-L)
      Psychiatry teams operate within non-psychiatric settings and are dedicated to the
      mental health care of patients presenting in these areas. Their unique skills and
      approaches offer support and education to these non-psychiatric teams and care to
      this group of patients. They are thus ideally placed to assess, diagnose and
      manage individuals presenting with somatoform disorders. Unfortunately, these
      teams are not widely available, largely because the current climate within
      psychiatry leads services to concentrate on what is defined as serious mental
      illness, a term usually used synonymously with psychotic disorders, despite the
      large number of people suffering from somatoform disorders and the cost of their
      care. The dislike that some colleagues have for this group of conditions may
      further hamper the creation of these services. In order to provide efficient
      assessment of and treatment for individuals with somatoform disorders, C-L
      Psychiatry teams must be created to lead clinical development, research and
      training in this discipline. These teams will also lead on the further research
      required.

PMID- 16451884
TI  - Somatoform disorders, somatization and abnormal illness behaviour.
AB  - Somatization and abnormal illness behaviour (AIB) often co-exist, and their inter
      relationship appears to be complex. Patients with somatization are often observed
      to demonstrate abnormal illness behaviour. On the other hand, somatization has
      been explained in terms of abnormal illness behaviour. The exact cause-effect or
      any other relationship is not fully understood. This review examines the
      available evidence to understand these two clinically important, common and
      interrelated phenomena, their measurements and management. Many studies have
      confirmed that occurrence of multiple somatic symptoms as the chief or presenting
      complaints are highly suggestive of abnormal illness behaviour. Recognition of
      AIB in somatoform disorders is important in order to avoid unnecessary tests,
      inappropriate treatment, and to prevent encouragement and reinforcement of
      abnormal behaviours.

PMID- 16451883
TI  - Behavioural mechanisms and cognitive-behavioural interventions of somatoform
      disorders.
AB  - Due to the lack of adequate cure or medication for somatoform disorders,
      cognitive-behavioural intervention or cognitive-behavioural therapy (CBT) seems
      to be an optimal treatment resource for patients with these disorders, since the
      cause of the somatoform disorders cannot to be explained by medical illness, but
      can be analyzed in the process of both responding and operant conditioning.
      According to the reviews, randomized controlled trials are limited, but the
      efficacy of the intervention is quite impressive. Most of the studies use
      multiple treatment strategies, and no standardized treatment methods have been
      established. In general, the following steps are taken in CBT treatments: (1)
      assessment; (2) rationale of treatment choice; (3) course of treatment; (4)
      evaluation of treatment; and (5) reviewing treatment effects. In CBT, functional
      analysis in the assessment session is the key to success, to identify the
      relationship among discriminative stimuli and consequences, in order to reduce
      the undesirable behaviour, and the most effective approach of the treatment would
      be a combination of multiple techniques. However, as the efficacy of the
      treatments is established, expansion of accurate knowledge of functional analysis
      and training sessions for health care providers and patients should be provided.
      Further research should explore the effect of individual techniques, and
      comparison should be made to identify the relative benefits of the techniques
      using both individual, and group format.

PMID- 16451885
TI  - AMEE Education Guide no. 28: the development and role of departments of medical
      education.
AB  - A department of medical education is becoming an essential requirement for a
      medical school. This publication is intended for those wishing to establish or
      develop a medical education department. It may also prove useful to teachers in
      medicine by providing information on how such a department can support their
      activities. This will vary with the local context but the principles are
      generalizable. Medical education departments are established in response to
      increased public expectations relating to healthcare, societal trends towards
      increased accountability, educational developments, increased interest in what to
      teach and how to educate doctors and the need to train more doctors. The
      functions of a department of medical education include research, teaching,
      service provision and career development of the staff. The scope of its
      activities includes undergraduate and postgraduate education, continuing
      professional development and continuing medical education. These activities may
      be extended to other healthcare professions. Flexibility is the key to staffing a
      department of medical education. Various contractual arrangements, affiliations
      and support from non-affiliated personnel are needed to provide a multi
      professional team with a range of expertise. The precise structure of the
      department will depend on the individual institution. The name of the department
      may suggest its position within the university structure. The director provides
      academic leadership for the department and his/her responsibilities include
      promotion of staff collaboration, fostering career development of the staff and
      establishing local, regional and international links. Financial support may come
      from external funding agencies, government or university sources. Some
      departments of medical education are financially self-supporting. The department
      should be closely integrated with the medical school. Support for the department
      from the dean is an essential factor for sustainability. Several case studies of
      medical education departments throughout the world are included as examples of
      the different roles and functions of a department of medical education.

PMID- 16451886
TI  - Challenges facing PBL tutors: 12 tips for successful group facilitation.
AB  - One of the main tasks of a problem-based learning (PBL) tutor is to facilitate
      group discussion. Group facilitation is about process rather than content. In
      this process, a tutor helps the group increase their skills and progress in their
      discussion. Several studies have highlighted strategies and training used in
      preparing PBL tutors. However, PBL tutors usually feel that it is not that easy
      to change their teaching style to the PBL format. They are sometimes unsure about
      their role or what strategy they might use to facilitate their students'
      discussion. This article in the '12 Tips' series is a detailed description of,
      and provides answers to, common challenges faced by PBL tutors. The tips provided
      in this manuscript should help tutors with practical answers. The article may be
      useful to PBL tutors, medical and health educators and those responsible for PBL
      training workshops.

PMID- 16451887
TI  - How we changed from paper to online education: Teaching Immunization Delivery and
      Evaluation.
AB  - This article discusses meeting the challenges encountered in changing a paper
      based, interactive immunization delivery curriculum into an online, self-paced
      format. The program, TIDE (Teaching Immunization Delivery and Evaluation), was
      developed through collaborative efforts of medical educators and content experts
      with initial funding from the Centers for Disease Control and Prevention, the
      Ambulatory Pediatric Association and the Medical University of South Carolina. We
      summarize the efforts of the development team to create interactive case
      scenarios, provide ready access to resource materials and an audit tool for
      assessing the immunization rate of the learner's clinic or practice, and meet the
      rigorous requirements of awarding continuing education credit. Data based on more
      than 100 doctors' and nurses' evaluations indicate a trend toward higher overall
      ratings of the online version than the paper version (88% online vs. 76% paper
      reported module as very good or excellent). As the TIDE program is evaluated, the
      team's goal is to incorporate instructional methods to increase relevance and
      learners' opportunities for 'learning by doing.' Future plans include extending
      online office assessment tools to encourage use for continuous quality
      improvement, and providing a mechanism for learners to share their techniques for
      obtaining and maintaining high immunization rates.

PMID- 16451888
TI  - An update on master's degrees in medical education.
AB  - Planning and implementing educational programs in medicine optimally requires a
      background in educational theory and practice. An avenue of training open to such
      practitioners is a master's degree in medical education. A single 1998 report
      lists the programs known at that time and information about them remains scarce.
      The authors have re-examined all current programs offering master's degrees in
      medical or health sciences education in the English-speaking world, including the
      Netherlands. The authors contacted the programs identified in the 1998 report to
      establish how many were still in operation. The search was extended using Pubmed
      and other search engines. A further verification targeted a selected sample of 10
      prominent US medical schools. Twenty-one currently operating programs were
      identified: six in the US, eight in the UK, three in Canada, three in Australia
      and one in Holland. Seven of nine original master's programs were still in
      existence. URLs, website and other logistical information about each program are
      tabled. A master's degree in medical or health sciences education is the most
      specific method for medical faculty to obtain a credentialed grounding in
      educational theory and practice. The authors provide up-to-date contact
      information for current programs and summarize other related essential logistical
      data.

PMID- 16451889
TI  - Junior faculty experiences with informal mentoring.
AB  - Mentoring is one way in which new faculty can acquire the skills needed for a
      successful academic career. Little is known about how informal mentoring is
      operationalized in an academic setting. This study had two main objectives: (1)
      to determine if junior faculty identify as having an informal mentor(s) and to
      describe their informal mentoring relationships; and (2) to identify the areas in
      which these faculty seek career assistance and advice. The study employed a
      grounded theory approach. Subjects were recruited from the clinical teaching
      faculty and were 3-7 years into their first faculty position. Theoretical
      sampling was employed in which data analysis proceeded along-side data
      collection, and collection ceased when saturation of themes was reached.
      Saturation was reached at ten subjects. Data were collected by individual
      interviews. Four topics recurred: qualities sought in mentors, processes by which
      guidance is obtained, content of the guidance received and barriers. Faculty
      obtained guidance in two principal ways: (a) through collegial working
      relationships; and (b) through discussion with senior clinicians as part of the
      evaluative system in the department. Participants discussed the degree of
      mentoring they received in the areas of: career focus, orientation to the
      organization, transition of role from trainee to faculty and work/nonwork
      balance. Barriers identified included an evaluative role and conflict of interest
      on the mentor's part. Junior faculty identify some relationships from which they
      receive guidance; however, limitations in these relationships result in a lack of
      mentorship on career direction and on balancing career with personal life.

PMID- 16451890
TI  - The elusive content of the medical-school curriculum: a method to the madness.
AB  - A major problem for curriculum and course planners is coping simultaneously with
      the expanding knowledge base and having less time to teach. A widely used
      solution is to include huge amounts of information in the curriculum. A better
      solution is to identify a manageable core of relevant knowledge. One way is to
      begin with program goals and systematically identify content with increasing
      specificity that would be needed to achieve those goals. Another is the empirical
      determination of content, which has not been widely attempted. These studies
      would include experiments and practice analyses. There is a need to mount greater
      and more rigorous efforts to help advance the scholarship and to provide useful
      information to curriculum planners. Large-scale, multi-site studies that compare
      the results from various methods and from different sources will be more useful
      to medical education generally. In these days of exploding information and
      technology and greater understanding of how people learn, more than ever, efforts
      need to be focused on finding the very specific content that will result in the
      best learning for our students.

PMID- 16451891
TI  - Assessment of professional attitude and conduct in medical undergraduates.
AB  - One year after implementation of a new schedule of summative assessment of
      professional attitude and conduct (AC) for medical undergraduates at the
      University of Wales College of Medicine (UWCM), we evaluated its effectiveness
      and obtained feedback of the perceptions of participating teachers and students.
      An anonymous questionnaire was administered to all 4th year students and their
      clinical teachers. Four out of 180 students actually failed to complete the 4th
      year as a result of unsatisfactory AC. Of these, three students were identified
      as having a problem which benefited from supportive remediation. One hundred and
      twenty out of 244 (49%) teachers and 166 out of 195 (85%) students completed the
      feedback questionnaires. The majority of students and teachers agreed that AC
      should be an integral part of their assessment. However, several problems were
      highlighted, in particular, students' perception that marks were sometimes based
      on assessment of knowledge rather than attitude and conduct and teachers'
      reluctance to identify unprofessional behaviour in students. The use of
      longitudinal assessment of professional AC was found to be effective at
      identifying students with persistent AC problems and also provided an opportunity
      for formative experience. The reluctance of teachers to identify negative
      behaviours, compared to deficiencies in skill and knowledge, is an important
      aspect of developing a reliable method of evaluating professional attitudes.

PMID- 16451892
TI  - Students' conceptions of the medical profession; an interview study.
AB  - Students' beliefs and attitudes towards the medical profession have been studied
      in relation to career choices, but most research has been restricted to either
      predetermined aspects or to a limited number of specialties. This study aimed at
      getting unprompted insight in the students' perceptions of their future
      profession in dimensions that may be determinants of study success and career
      choice. Undergraduate and graduated medical students were interviewed and asked
      to characterize the medical profession in general and four contrasting
      specialties in particular. Grounded Theory methodology was used to analyse the
      data. Participants were medical students at the start of their training (n = 16),
      during clerkships (n = 10) and after graduation (n = 37). Beginning students
      perceive the medical profession in limited dimensions: the activities of a
      physician, their relationship to patients and the physician's knowledge, skills
      and personality. They do not see many differences between specialties, in
      contrast with students with clinical experience and graduate students.
      Undergraduate students' perception is focussed more on social aspects of the
      profession compared to graduates.

PMID- 16451893
TI  - Cultivating psychological well-being in Hong Kong's future doctors.
AB  - There has been much recent attention on psychological well-being and pastoral
      care for medical students. This study examines psychological morbidity
      (depression, anxiety and stress) in Hong Kong medical students, as well as their
      concerns, coping mechanisms and their help-seeking. Medical students in Hong Kong
      reported a higher level of psychological morbidity as compared with other
      tertiary education students. Their main concerns include examinations, stress,
      career, adjusting to the new medical curriculum and commitment to the course. The
      coping skills adopted were largely adaptive. Maladaptive coping skills like
      'denial', 'self-blame' and 'behavioural disengagement' were highly correlated
      with depression, anxiety and stress scores. Most of the students concerned wanted
      support services that were specifically tailored to their needs and at least
      partly provided by people who had been through medical training themselves. The
      faculty at the University of Hong Kong is establishing a Programme for Effective
      Transition and Student Support (PETSS) to provide a multi-faceted support system
      for its medical students. The findings in this study help to ensure that the
      services provided will be relevant, accessible and acceptable to the students.

PMID- 16451894
TI  - Student-selected components in the undergraduate medical curriculum: a multi
      institutional consensus on assessable key tasks.
AB  - This paper describes further progress by the Northern Universities SSC Consortium
      in achieving consensus on the contribution of the Student Selected Components
      (SSCs) to undergraduate medical courses. Following the identification of common
      purposes and outcomes, the group has matched these to assessable key tasks which
      students may undertake in order to demonstrate competence on a range of
      attributes not normally fully assessed in the core curriculum. In some schools,
      SSCs may be the predominant route through which students gain exposure to
      research methods and reflective practice. In addition to opportunities to acquire
      knowledge and skills outside the core curriculum, SSCs can contribute towards
      enhancement of core skills. SSCs may also contribute to the overall longitudinal
      assessment of personal and professional development. The potential role of
      portfolios in maximizing student learning from SSCs is discussed, and future
      areas for development identified.

PMID- 16451895
TI  - The relative importance of individual and organizational factors for the
      prevention of job stress during internship: a nationwide and prospective study.
AB  - This study aimed to investigate the relative and sequential importance of
      individual and organizational predictors of job stress associated with medical
      internship work. All medical students who graduated in Norway over 2 years (n =
      631) were surveyed and followed up 1 year later at the end of the hospital
      internship year. The outcome was job stress as a house officer; predictor
      variables included individual factors at medical school and work-related factors
      during internship. A total of 371 (58%) responded at both time points. Adjusted
      predictors of job stress were: vulnerability (neuroticism) personality trait
      (beta 1.7 [95% CI, 0.94 to 2.5]); perceived recording skills (beta -0.43 [-0.78
      to -0.08]); number of hours of sleep when on call (beta -2.3 [-3.6 to -1.0]); and
      learning environment on the hospital wards (beta -0.56 [-0.82 to -0.30]) (see
      table 2). The vulnerability trait was especially important among the female
      interns. The predictors explained 29% of the total variance in the model;
      personality contributed 16% of the variance, perceived recording skills 4% and
      the organizational factors measured in the internship year explained 9%. In terms
      of prevention, both individual factors (personality trait and perceived skills)
      and organizational work-related factors (sleep deprivation and learning
      environment on the wards) should be considered.

PMID- 16451896
TI  - Medical students' perceptions of mentoring: a focus-group analysis.
AB  - Characteristics of medical students' mentoring relationships and factors that
      affect mentoring during medical school are poorly understood. The authors
      conducted four focus groups with fourth-year medical students to explore what
      students sought from mentors, perceived barriers to mentoring and suggestions for
      improvement. Data were analyzed using grounded theory. Students with and without
      mentors described a mentoring relationship as a personal connection with a
      faculty member invested in helping the student achieve a personal and
      professional vision. The short duration of courses, abrupt change from classroom
      learning to clerkships and limited exposure to clinicians were perceived as
      barriers to mentoring. Students recommended that the school explicitly promote
      mentoring with early education about finding mentors, placing the responsibility
      on students while also expanding the pool of potential mentors. It is concluded
      that medical students characterize mentoring in terms of the interpersonal
      dynamics of the relationship, emphasizing personal connection and advocacy.
      Educating and empowering students along with faculty education regarding
      students' needs may improve mentoring.

PMID- 16451897
TI  - Views of family medicine department Chairs about mentoring junior faculty.
AB  - Mentoring can be a key component contributing to the success of faculty. We
      investigated the attitudes of family medicine department Chairs toward mentoring,
      with emphasis on mentoring female and minority faculty. This qualitative inquiry
      used semi-structured interviews with 13 Chairs of US departments of family
      medicine. Although most Chairs felt that mentoring had value, a minority of our
      sample had formal mentoring programs. Multiple mentors were suggested for female
      and minority faculty to meet both their personal career and content needs.
      Availability of senior faculty is a key resource. Until more senior women and
      minority faculty are available, cross-gender and cross-ethnicity mentoring will
      need to be utilized.

PMID- 16451898
TI  - Does change from a traditional to a new medical curriculum reduce negative
      attitudes among students? A quasi-experimental study.
AB  - The authors investigated whether a new type of medical school curriculum-with
      problem-based learning, integrated preclinical and clinical phases, and increased
      levels of contact between students, patients and teachers--is associated with
      lower levels of students' negative attitudes towards medical training than is a
      traditional medical school curriculum. This association was found, and was
      confirmed by a comparison between students in a university that had changed from
      a traditional curriculum to a new curriculum. Curriculum design may explain
      differences in students' attitudes towards medical school.

PMID- 16452049
TI  - Long-term effect of pentoxifylline and NG-nitro-L-arginine methyl ester on
      testicular function in spermatic artery ligation.
AB  - OBJECTIVE: To investigate long-term testicular function in pentoxifylline- and NG
      nitro-L-arginine methyl ester (L-NAME)-treated rats prior to spermatic artery
      ligation by assessing serum inhibin B concentration, a reliable endocrine marker
      of spermatogenesis. MATERIAL AND METHODS: Forty prepubertal rats were randomly
      divided into four equal groups. Right orchiectomy was performed in all rats.
      Intraperitoneal pentoxifylline and L-NAME were administered to Groups 1 and 2,
      respectively. Rats in Group 3 did not receive any medication. The spermatic
      arteries of the left testes were ligated in all groups with the exception of the
      sham controls (Group 4). One month postoperatively, a histopathologic evaluation
      was performed and serum inhibin B concentrations were assessed in all groups.
      RESULTS: There were no statistically significant differences in testis size or
      serum inhibin B concentration between Groups 1, 2 and 3. However, the testes were
      significantly smaller (p(1)=0.01, p(2)=0.01, p(3)=0.01) and serum inhibin B
      levels were significantly decreased (p(1)=0.01, p(2)=0.01, p(3)=0.01) when Groups
      1-3 were compared with Group 4. Histopathological evaluations revealed necrosis
      and calcification in all specimens with the exception of the sham-operated group.
      CONCLUSIONS: The long-term outcomes of spermatic artery ligation were poor and
      testicular atrophy developed in rat testes in all study groups. Testicular
      atrophy could not be reversed by preoperative administration of pentoxifylline
      and L-NAME.

PMID- 16452050
TI  - Protective role of natural antioxidant supplementation on testicular tissue after
      testicular torsion and detorsion.
AB  - OBJECTIVES: To investigate the impact of garlic extract (GE), which is known for
      its antioxidant activity, on a testicular torsion/detorsion model in animals and
      to help understand how to prevent both ischemic and reperfusion injuries after
      testicular torsion and detorsion. MATERIAL AND METHODS: Six groups of rats (n=7
      in each group) were used. The animals in the control group (Group I) did not
      receive any treatment. The animals in the sham group (Group II) underwent scrotal
      incision and testicular fixation only. The animals in Groups III-VI underwent 720
      degrees of left testicular torsion for 2 h; subsequent detorsion was performed
      for 2h in Groups IV and VI only. Animals in Groups V and VI were treated exactly
      the same as those in Groups III and IV, respectively except that they were
      pretreated with oral GE for 5 days at a dosage of 5 ml/kg. Both testicles in all
      rats were removed and tissue malondialdehyde (MDA) levels and enzymatic
      activities of xanthine oxidase (XO) were studied, in addition to a histological
      evaluation after hematoxylin-eosin staining. RESULTS: Testicular MDA levels and
      XO activities were higher in Group III compared to Group II (p<0.05).
      Pretreatment with GE prevented these increases. Detorsion caused more damage and
      resulted in a further increase in MDA levels but MDA levels were not increased in
      animals pretreated with GE. Histologically, torsion caused some separation
      between germinative cells in the seminiferous tubules, which became much more
      prominent in Group IV and was attenuated by GE pretreatment. There were no
      significant changes in any of the above-mentioned enzymatic activities or
      histopathologic changes in the contralateral testicle in any of the groups.
      CONCLUSIONS: We believe that both testicular torsion and detorsion result in
      testicular tissue damage by means of lipid peroxidation, which is evident by an
      increase in the tissue levels of MDA. Dietary supplementation with GE seems to
      attenuate the generation of toxic free radicals, as evidenced indirectly by low
      tissue MDA levels.

PMID- 16452051
TI  - CHEK2*1100delC is not an important high-risk gene in families with hereditary
      prostate cancer in southern Sweden.
AB  - OBJECTIVE: CHEK2*1100delC is a frame-shifting germ-line mutation which abolishes
      the function of cell-cycle-checkpoint kinase 2 (chk2) and hence impairs the
      cells' response to DNA damage. This variant occurs in 1% of the general Western
      population but has been reported to be more common among patients with breast and
      prostate cancer. The aim of this study was to investigate the significance of
      CHEK2*1100delC as a possible high-risk gene for hereditary prostate cancer in the
      population of southern Sweden. MATERIAL AND METHODS: We screened for the
      CHEK2*1100delC variant in 419 men diagnosed with prostate cancer in southern
      Sweden, 145 of whom were sporadic cases that were divided into two subgroups
      depending on whether they were diagnosed before (n=64) or after (n=81) the age of
      55 years. A further 126 men were classified as familial prostate cancer cases and
      148 as hereditary prostate cancer cases. The control group consisted of 305
      military conscripts aged 18 years (range 18-21 years). RESULTS: The
      CHEK2*1100delC variant was found in 1.2% of the cases (sporadic: 0.7%; familial:
      1.6%; hereditary: 1.4%) and in 1.0% of the controls. CONCLUSION: The CHEK2
      1100delC mutation is not a clinically important high-risk gene for hereditary
      prostate cancer susceptibility in the population of southern Sweden.

PMID- 16452052
TI  - Screening for bladder tumours in men aged 60-70 years with a bladder tumour
      marker (UBC) and dipstick-detected haematuria using both white-light and
      fluorescence cystoscopy.
AB  - OBJECTIVE: To investigate the relevance of bladder tumour screening using
      haematuria dipsticks and a bladder tumour marker in a random selection of men,
      age 60-70 years, from a well-defined geographical area using both fluorescence
      and white-light cystoscopy. MATERIAL AND METHODS: A total of 2000 randomly
      selected men, age 60-70 years, were invited by mail to participate in a screening
      for bladder tumours by having their urine tested with a dipstick for haematuria
      and a bladder tumour marker (UBC). Men with 5-10 red blood cells (RBC)/microl and
      an International Prostate Symptom Score (IPSS) of >10 and all men with =25
      RBC/microl and/or elevated UBC levels underwent both white-light and fluorescence
      cystoscopy. RESULTS: A total of 1096 men (55%) responded and were included in the
      study. The incidence of 5-10 RBC/microl was high: 14%. A tumour was detected in
      one of the 62 men with 5-10 RBC/microl and an IPSS of >10. Among the 10% of men
      (n=112) with =25 RBC/microl, four bladder tumours were detected. Another two
      tumours were detected in men without haematuria (positive UBC test). No tumours
      were observed using only fluorescence cystoscopy. CONCLUSIONS: Fluorescence
      cystoscopy and the UBC test were of no use in this screening situation. The
      incidence of haematuria (=5-10 RBC/microl) was so high (1:4) that this borderline
      for bladder tumour screening appears unrealistic. The incidence of =25 RBC/microl
      was 1:10 and one of 28 cystoscopies revealed a bladder tumour. All seven tumours
      were detected in men who were or had been smokers. A haematuria-based screening
      among older male smokers with =25 RBC/microl on dipstick testing is thus an
      option that should be considered.

PMID- 16452053
TI  - Reboxetine in therapy-resistant enuresis: results and pathogenetic implications.
AB  - OBJECTIVE: To investigate whether the norepinephrine reuptake inhibitor
      reboxetine is effective as a non-cardiotoxic alternative to imipramine in the
      treatment of therapy-resistant enuresis. MATERIAL AND METHODS: Twenty-two
      children with severely socially handicapping enuresis resistant to urotherapy,
      the enuresis alarm, desmopressin and anticholinergics (all children had tried all
      these treatments) were given reboxetine, 4-8 mg at bed-time, for compassionate
      reasons. RESULTS: Thirteen of the children (59%) achieved complete dryness with
      reboxetine, either as monotherapy or combined with desmopressin. Side-effects
      were minor and did not lead to discontinuation of treatment. CONCLUSIONS:
      Although the results of this study need to be confirmed in randomized, placebo
      controlled trials, reboxetine may prove to be a useful treatment for therapy
      resistant nocturnal enuresis.

PMID- 16452054
TI  - Effect of acute acid loading on acid-base and calcium metabolism.
AB  - OBJECTIVE: To investigate the acid-base and calcium metabolic responses to acute
      non-carbonic acid loading in idiopathic calcium stone-formers and healthy males
      using a quantitative organ physiological approach. MATERIAL AND METHODS: Five-h
      ammonium chloride loading studies were performed in 12 male recurrent idiopathic
      calcium stone-formers and 12 matched healthy men using a randomized, placebo
      controlled, cross-over design. Arterialized capillary blood, serum and urine were
      collected hourly for measurement of electrolytes, ionized calcium, magnesium,
      phosphate, parathyroid hormone and acid-base status. Concentrations of non
      metabolizable base (NB) and acid (NA) were calculated from measured
      concentrations of non-metabolizable ions. RESULTS: The extracellular acid-base
      status in the stone-formers during basal conditions and acid loading was
      comparable to the levels in the healthy controls. The stone-formers tended to
      have lower renal excretion rates of NA during acid loading; however, for a given
      degree of non-carbonic acidosis, controls and stone-formers excreted
      approximately the same amount of NA in the urine, suggesting that the capacity of
      tubular regeneration of NB was comparable in the two groups. Acid loading
      resulted in significantly increased concentrations of ionized calcium in serum in
      both controls and stone-formers. The increase in serum ionized calcium in
      response to acid loading was, however, significantly higher in the calcium stone
      formers than in the healthy individuals. Acid loading resulted in massive
      calciuria in both groups, with significantly higher urinary calcium excretion
      rates in the stone-formers compared to the healthy subjects. Renal excretion
      rates of NA correlated significantly with renal calcium excretion rates in both
      groups. However, the stone-formers excreted significantly more calcium in the
      urine at a given rate of renal NA excretion. CONCLUSIONS: The hypercalciuric and
      hypercalcaemic responses to loading with non-carbonic acid are more pronounced in
      recurrent idiopathic calcium stone-formers than in healthy individuals. Acid
      loading (i.e. protein ingestion) may contribute to disturbed bone metabolism in
      idiopathic calcium nephrolithiasis as well as calcium stone formation.

PMID- 16452055
TI  - Body size and weight as predisposing factors in varicocele.
AB  - OBJECTIVE: The literature regarding the constitutional type of children and
      adolescents with varicocele is inconsistent. The aim of this investigation was to
      examine a possible influence of weight, height and body mass index (BMI) on the
      formation of varicoceles during childhood and adolescence. MATERIAL AND METHODS:
      In a retrospective data analysis, 193 Caucasian children and adolescents aged 9
      19 years (mean age 14.7 years) with left-sided varicocele grade 2-3 were studied.
      The weight, height and BMI of the subjects were compared with the age-correlated
      normal values currently accepted in Germany. Additionally, the familial
      disposition for varicocele and the occurrence of relevant concurrent diseases
      were considered. RESULTS: In the group of patients examined, the mean percentiles
      of weight (57th) and height (58th) were significantly above and the mean BMI
      percentile (42th) was significantly below the age-correlated 50th percentile for
      the normal population (p=0.019, 0.005 and 0.002). In our case material, 12.2% of
      all brothers of the patients had varicoceles. CONCLUSIONS: The results of this
      investigation suggest a correlation between physical appearance and the formation
      of a varicocele during childhood or adolescence. We were able to demonstrate that
      patients with varicocele were heavier and taller than an age-correlated normal
      population, but had a distinctly lower BMI. Further studies are needed to verify
      whether this rather athletic habitus, together with the postulated difference in
      muscle:fat ratio, represents an important etiologic factor for varicocele
      formation.

PMID- 16452056
TI  - Evaluation of patients after treatment of arterial priapism with selective micro
      embolization.
AB  - OBJECTIVE: Arterial (high-flow) priapism is characterized by a prolonged non
      painful erection without sexual arousal as a result of unregulated inflow of
      blood to the corpus cavernosum. Treatment is based on decreasing this elevated
      inflow, primarily by means of selective arteriography and embolization. The aim
      of this study was to evaluate the treatment of patients with arterial priapism.
      MATERIAL AND METHODS: In the period between 1990 and 2004, 10 patients with
      arterial priapism were admitted to our department. The mean age when priapism
      developed was 32 years (range 11-62 years). Eight patients were treated with
      selective embolization, one was operated on and one refused treatment. Nine
      patients completed a standardized questionnaire which included the International
      Index of Erectile Function (IIEF-5). The mean follow-up time after treatment was
      70 months. RESULTS: All patients treated with selective embolization achieved
      reduced tumescence. Six out of eight patients had an improved IIEF-5 score after
      treatment. In nine men, the etiology of the arterial priapism was perineal
      trauma. In one case, an anomaly with an accessory artery to the corpus cavernosum
      was diagnosed, which required surgery, and in one case recurrence of the priapism
      necessitated a second embolization. CONCLUSIONS: Selective embolization results
      in reduced tumescence and an improvement in erectile function in patients with
      arterial priapism. Trauma to the perineum was the main etiology in this study.

PMID- 16452057
TI  - Ureteroscopic management of urological complications after renal transplantation.
AB  - OBJECTIVE: To determine the feasibility, safety and efficacy of diagnostic and
      therapeutic ureteroscopy in renal allograft ureters. MATERIAL AND METHODS: We
      reviewed 1560 consecutive renal allografts performed between June 1989 and
      February 2002. A total of 28 patients (1.8%) had indications for an endoscopic
      procedure on the allograft ureter, as follows: obstructive ureteral calculi with
      a history of failed extracorporeal shock-wave lithotripsy, n=6; suspected
      ureteral stricture, n=3; upwardly migrated ureteral stents, n=9; and ureteral
      stricture at the ureteroneocystostomy site, n=10. Ureters were anastomosed to the
      bladder using the Leadbetter-Politano and Lich-Gregoire methods in six and 22
      cases, respectively. Ureteroscopies were performed with a semi-rigid 9.8 F Wolf
      ureteroscope. RESULTS: Identification of the ureteral orifice and insertion of a
      guide-wire into it was successful in 19 cases (68%). If we exclude the 10
      patients with ureteral stricture, ureteroscopy was successful in 13/18 cases
      (72%). Four ureteral calculi (67%) were removed with the ureteroscope. Seven out
      of nine migrated stents (78%) were retrieved. Four patients with ureteral
      stricture at the ureteroneocystostomy site (40%) underwent successful ureteral
      dilatation and double-J ureteral catheters were also inserted. Diagnostic
      ureteroscopy was successful in all cases. Two complications (one urinary leakage
      and one symptomatic urinary tract infection) occurred and were managed
      conservatively. CONCLUSIONS: Ureteral endoscopy is a safe and effective method
      for the management of urological complications after renal transplantation. This
      procedure can be considered the first choice, in preference to percutaneous and
      antegrade modalities.

PMID- 16452059
TI  - Effects of N-acetylcysteine on radiocontrast nephropathy in rats.
AB  - OBJECTIVE: N-acetylcysteine (NAC) has yielded some promising results recently in
      the prevention of radiocontrast nephropathy (RCN). In this study, the structural
      and functional effects of NAC on RCN were analyzed. MATERIAL AND METHODS: Twenty
      eight Wistar rats were randomized into four groups, as follows: Group 1,
      controls; Group 2, contrast; Group 3, contrast+NAC; and Group 4, NAC. All rats
      were deprived of water for 24 h and then contrast medium (ioxoglate; 10 ml/kg)
      was administered to Groups 2 and 3. NAC (50 mg/kg) was introduced enterally to
      Groups 3 and 4 at a dose of 50 mg/kg in 0.5 ml of distilled water, in four
      sequential doses 12h apart, starting after 12?h of water deprivation. After 4
      days, rats were sacrificed. Creatinine clearance was calculated. The
      malondialdehyde (MDA) level was quantified in tissue samples. Slides stained with
      hematoxylin-eosin and periodic acid-Schiff were examined by means of light
      microscopy. Each tubular cross-section from all images was scored as either mild
      (preserved brush border, no necrosis), moderate (loss of brush border, no
      necrosis) or severe (loss of brush border accompanied by necrosis) and the
      frequencies of these lesion severities were compared. RESULTS: Mean baseline
      serum creatinine levels and creatinine clearances were similar in all groups.
      Mean serum creatinine level increased significantly only in Group 2 (0.6+/-0.1 vs
      0.7+/-0.2 mg/dl; p<0.05). Tissue MDA levels were similar in all groups. Moderate
      (13.8%+/-1.5% vs 42%+/-1.4%; p<0.05) and severe (0% vs 40%+/-2.1%; p<0.05)
      lesions were significantly more frequent in Group 2 compared to Group 1. The
      frequency of severe lesions in Group 3 was found to be halved compared to that in
      Group 1 (40%+/-2.1% vs 20.2%+/-0.86%; p<0.05). CONCLUSION: NAC protects the
      kidneys following exposure to contrast medium as it decreased the severity of
      tubular lesions in rats.

PMID- 16452058
TI  - Fucoidin, an inhibitor of leukocyte adhesion, exacerbates acute ischemic renal
      failure and stimulates nitric oxide synthesis.
AB  - OBJECTIVES: To lessen renal ischemic injury caused by fucoidin, a substance
      capable of reducing tissue infiltration by neutrophils, and to seek a possible
      interrelationship with the nitric oxide system which may also modulate leukocyte
      infiltration. MATERIAL AND METHODS: Acute ischemic renal failure was induced in
      rats by uninephrectomy followed by 60 min of clamping of the renal artery. The
      rats were injected with fucoidin (25 mg/kg) or fucoidin+nitroprusside (2.5 mg/kg)
      before reperfusion, and urine was collected for 24 h afterwards. Serum and urine
      were examined for creatinine sodium and protein; creatinine clearance and
      fractional excretion of sodium (FENa) were calculated. The renal tissue of the
      sacrificed animals was examined histologically for tissue damage and
      histochemically for myeloperoxidase, a marker of neutrophil infiltration. The
      nitric oxide system was evaluated by measuring urinary nitrates and inducible
      nitric oxide synthase messenger RNA (iNOs mRNA). RESULTS: Renal failure was more
      severe in the fucoidin group than the nitroprusside group (creatinine clearance
      0.11+/-0.08 ml/min for ischemia+fucoidin versus 0.26+/-0.11 ml/min for ischemia
      only; p<0.002). Adding nitroprusside to fucoidin lessened the decline in
      creatinine clearance (0.13+/-0.13 ml/min; p=NS). Fucoidin was associated with
      greater tubular damage, as evidenced by increased FENa (7.2%+/-2.8% vs 1.51%+/
      1.96% for ischemia only; p<0.001). Nitroprusside weakened this trend. Fucoidin
      caused an increase in the fractional excretion of nitrates, a response
      accompanied by increased iNOS mRNA. CONCLUSIONS: Fucoidin failed to protect the
      kidney from ischemic damage and was even nephrotoxic. It also stimulated the
      formation of iNOS RNA.

PMID- 16452060
TI  - Use of the osmolal gap to guide the start and duration of dialysis in methanol
      poisoning.
AB  - OBJECTIVE: Rapid diagnosis and treatment of methanol poisoning is mandatory.
      Dependence on serum methanol analysis in this situation may delay diagnosis and
      treatment. The anion and osmolal gaps have been recommended for use as diagnostic
      tools, but the use of these gaps to evaluate the length of hemodialysis treatment
      has only been emphasized in a few reports. We evaluated the usefulness of the
      osmolal gap in estimating the need for dialysis and the duration of this
      treatment in 17 methanol-poisoned subjects. MATERIAL AND METHODS: Patients were
      part of a recent outbreak of methanol poisoning, in which the diagnosis upon
      admission was mainly based on use of the anion and osmolal gaps. The duration of
      dialysis generally followed the standard recommendation of 8h. During dialysis,
      blood samples were frequently collected and analyzed to determine acid-base
      status and serum methanol and to calculate the osmolal gap. In nine patients, the
      duration of dialysis was compared with the duration necessary to normalize serum
      methanol and the osmolal gap. RESULTS: There was a good correlation between serum
      methanol and the osmolal gap during hemodialysis (y=1.09x+3.82; R(2)=0.92). The
      osmolal gap therefore gives a good estimate of the serum methanol level during
      hemodialysis, and could have saved a total of 23 h of dialysis treatment (34%) in
      nine patients had it been applied. CONCLUSIONS: In the absence of serum methanol
      analyses, the osmolal gap is useful to assess the indication for and duration of
      hemodialysis in methanol-poisoned patients. In mass poisoning situations, use of
      the osmolal gap makes it possible to reduce the duration of dialysis in a safe
      manner.

PMID- 16452061
TI  - Inguinal metastasis of a bladder mixed carcinoma with predominant adenocarcinoma
      component.
AB  - We report a case of urinary bladder mixed carcinoma with inguinal metastasis.
      Histological examination of the transurethral resection specimens revealed
      adenocarcinoma with small foci of squamous and transitional cell carcinomas. A
      right inguinal metastasis occurred 1 year after radical cystourethrectomy.
      Chemotherapy and radiotherapy were performed but the metastatic tumor remained
      unchanged.

PMID- 16452062
TI  - Chest drain insertion may result in the acute scrotum.
AB  - Pneumoscrotum is an extremely rare occurrence following a variety of procedural
      and pathological causes. We describe a case following multiple chest drain
      insertions which was managed conservatively. It is important to differentiate
      pneumoscrotum from other causes of acute scrotum as it may precede a serious
      pathology and may require medical or surgical intervention.

PMID- 16452063
TI  - Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine
      for initial treatment of HIV-1 infection: TONUS study.
AB  - BACKGROUND: To assess the efficacy and safety of the triple NRTI combination of
      abacavir (ABC), lamivudine (3TC), and tenofovir (TDF) in a once-daily regimen.
      METHOD: 38 HIV-naive patients (pts) were treated in a prospective open-arm study
      over 48 weeks (W48). Virological failure was defined as never achieving plasma
      HIV-1 RNA < 400 copies/mL or rebound of > or = 0.7 log10. RESULTS: 12/36 (33%)
      pts had virologic failure at W24 and 10 additional pts had HIV RNA > 50 copies/mL
      at W12 or W24. There was a significant association between baseline viral load
      (VL) and virologic failure in 0%, 29%, and 64% pts with baseline VL levels < 4, 4
      5, and > 5 log10 copies/mL, respectively (p = .014). 76% of pts developed K65R
      and M184V/I mutations by W24, and 19% developed M184V/I alone. At W4, 86% of pts
      had adequate plasma Cmin for the 3 drugs. 14 pts with K65R and M184V/I were given
      a rescue therapy with a successful outcome (< 50 copies/mL; median follow-up 48
      weeks). CONCLUSION: Convergent genetic pathway to resistance, in conjunction with
      lower antiretroviral potency, may explain the high rate of selection K65R and
      M184V mutations. These mutations did not appear to have a negative effect on
      rescue therapy with a variety of regimens.

PMID- 16452064
TI  - Prospective, open-label comparative study of liver toxicity in an unselected
      population of HIV-infected patients treated for the first time with efavirenz or
      nevirapine.
AB  - OBJECTIVE: To compare the two nonnucleoside reverse transcriptase inhibitors
      (NNRTIs) when first introduced in an antiretroviral regimen, a prospective open
      label assessment of the frequency, severity, risk factors, and outcome of
      hepatotoxicity was performed. METHOD: Liver enzymes were followed-up during 18
      months in patients who received efavirenz (EFV; 324 patients) or nevirapine (NVP;
      299). RESULTS: The two study groups were comparable, except for the lower
      baseline CD4+ count found in the EFV group. No differences were found when
      considering the type and duration of eventual prior anti-HIV therapy; frequency
      and length of protease inhibitors, methadone, or anti-tubercular drug use; HCV
      HBV co-infection; other hepatobiliary disorders; and alcohol-drug abuse. The
      frequency of overall and first-month drug interruption proved similar in the two
      study groups. A hepatotoxicity characterized by at least a 2-fold increase of
      transaminases versus baseline was significantly linked with NVP, and the number
      of patients showing hepatotoxicity tended to a reduction in the EFV group. Also
      the time to peak transaminase alterations was shorter in the NVP group. All
      significant differences regarding liver-pancreatic toxicities were controlled per
      eventual baseline hepatobiliary-pancreatic diseases, HIV stage, and concurrent
      drug therapies. DISCUSSION: Hepatotoxicity is a significant concern in the
      setting of antiretroviral-treated HIV disease. NVP-based HAART may be more
      hepatotoxic than EFV-based HAART, and a role is played by chronic liver
      disorders. Although concurrent hepatobiliary disorders and the possible
      hepatotoxicity of antiretrovirals do not represent contraindications to
      nonnucleoside inhibitor use, strict monitoring is recommended.

PMID- 16452065
TI  - Higher virological effectiveness of NNRTI-based antiretroviral regimens
      containing nevirapine or efavirenz compared to a triple NRTI regimen as initial
      therapy in HIV-1-infected adults.
AB  - PURPOSE: To compare outcomes of nonnucleoside reverse transcriptase inhibitors
      (NNRTIs) nevirapine or efavirenz versus abacavir-based regimens with a backbone
      of zidovudine and lamivudine as initial therapy of treatment-naive adults with
      HIV-1 infection in routine clinical care. METHOD: All patients starting their
      first antiretroviral therapy with any of the studied regimens from January 1999
      to December 2002 were included in the analysis. Rates of viral suppression (HIV
      RNA below 50 copies/mL) and discontinuation of any component of the regimen were
      compared at 48 weeks. RESULTS: Fifty-one patients started with one of the two
      NNRTI-based regimens and 49 started with the triple nucleoside regimen (3-NRTI).
      After 48 weeks, more patients in the NNRTI regimens (76.5%) than in the 3-NRTI
      (51.1%) regimen achieved a HIV-1 RNA level below the limit of detection (<1.7
      log10 copies/mL; p = .008). Time to change the antiretroviral regimen was shorter
      with 3-NRTI (median [range]: 234 [139-329] days) than with NNRTI (346 [0-756]
      days) (p = .0901). More withdrawals related to drug toxicity or intolerance
      occurred with the 3-NRTI-based regimen. CONCLUSION: In a routine clinical care
      setting, initial antiretroviral treatment with an NNRTI (nevirapine or efavirenz)
      plus zidovudine and lamivudine was virologically superior and safer than a 3-NRTI
      therapy (abacavir with the same NRTI backbone).

PMID- 16452066
TI  - Characteristics and prospects for hepatitis C therapy of an HIV-HCV coinfected
      population followed at a reference HIV center.
AB  - PURPOSE: A cross-sectional study was performed during 2004 at a large HIV clinic
      in Spain to identify HIV-HCV coinfected individuals who might be candidates for
      HCV therapy. METHOD: Plasma HCV RNA levels were measured in 405 anti-HCV antibody
      positive patients. Spontaneous HCV clearance had occurred in 11.4%. Overall, 165
      (40.1%) of HCV-HIV coinfected patients had already been exposed to interferon
      (IFN)-based therapies. Excluding those currently on treatment, the majority of
      them had either failed (64/142; 45.1%) or not completed therapy (25/142; 17.6%).
      Other 103 (25.4%) chronic HCV carriers refused treatment or were not considered
      as appropriate candidates, most often due to low CD4 counts or severe
      neuropsychiatric conditions. Treatment was deemed feasible and planned in the
      near future in 91 (22.5%) patients. Unfavorable HCV genotypes (1 and 4) were
      significantly more frequent in this group of individuals ready for HCV treatment
      compared to those who had cleared HCV in the past following IFN-based therapies.
      RESULTS: Spontaneous clearance of the HCV infection was low in HIV-coinfected
      patients. One third of our HIV-HCV coinfected population had already been exposed
      to HCV therapy, but only a minority had achieved sustained HCV clearance. Half of
      patients with active HCV replication never exposed to IFN were not considered as
      appropriate candidates for HCV therapy. CONCLUSION: More flexible criteria would
      considerably increase the number of patients to be treated with IFN-based
      therapy. The majority of patients ready to initiate HCV therapy have a poor
      therapeutic profile.

PMID- 16452067
TI  - Changes in body fat measured by DEXA in patients taking different formulations of
      stavudine.
AB  - BACKGROUND: Lipoatrophy is a frequent complication of chronic stavudine therapy.
      Stavudine extended release formulation (stavudine ER) gives lower peak and higher
      trough levels than the immediate release formulation (stavudine IR), and we
      hypothesized that the lower peak might result in less lipoatrophy. OBJECTIVE: To
      compare the rate of peripheral lipoatrophy between patients taking stavudine ER
      and stavudine IR. METHOD: Body composition was measured by dual energy X-ray
      absorptiometry (DEXA) every 6 months for 18 months in 29 patients taking either
      stavudine ER or IR as part of a randomized controlled clinical trial. RESULTS:
      DEXA fat measurements did not differ between the ER and IR groups at baseline,
      after a median of 32 months on stavudine-containing treatment. Over the 18 months
      of follow-up in the whole cohort limb fat decreased by a mean of 0.29 +/- 0.50 kg
      (p = .01) and leg fat percent decreased by a mean of 1.23% +/- 1.92% (p = .001),
      whereas trunk fat and trunk-to-limb fat percent ratio did not change
      significantly. There was no significant difference between the ER and IR groups
      in the rate of change of any of the fat parameters. At study completion, the
      proportion of patients with clinical lipodystrophy was similar in the stavudine
      ER and stavudine IR groups (67% and 64%, respectively; p = .893). CONCLUSION:
      Stavudine ER does not appear to cause less peripheral lipoatrophy.

PMID- 16452068
TI  - Six new cellulose synthase genes from Eucalyptus are associated with primary and
      secondary cell wall biosynthesis.
AB  - Higher plants contain a family of cellulose synthase catalytic subunit (CesA)
      genes that encode components of an enzyme complex embedded in the cell membrane.
      Recent studies in several higher plant species have demonstrated that two groups
      of CesA genes exist, associated with either primary or secondary cell wall
      deposition. We cloned six full-length CesA cDNAs from Eucalyptus grandis W. Hill
      ex Maiden (EgCesA1 through 6) and determined their expression patterns in a
      variety of organs from an adult tree. The six EgCesA genes encode predicted
      proteins of 978 to 1097 amino acid residues, each of which contains all of the
      key regions and motifs characteristic of functional CESA proteins. The predicted
      proteins share limited amino acid identity with each other, ranging from 61 to
      70%. In contrast, similar CESA proteins from higher plant species exhibit 81 to
      90% identity with the six EgCESAs. Gene expression analysis using quantitative
      reverse-transcription polymerase chain reaction indicated that transcripts of
      EgCesA1 to 3 were abundant in tissues enriched with cells laying down secondary
      cell walls (e.g., xylem), but were weakly expressed in tissues undergoing primary
      growth (e.g., unfolding leaves). Expression of EgCesA4 and EgCesA5 was
      upregulated in tissues rich in rapidly dividing cells undergoing primary wall
      synthesis, whereas EgCesA6 was weakly expressed in all tissues analyzed. These
      results suggest that Eucalyptus, like other higher plants, expresses two
      contrasting groups of apparently co-regulated CesAs involved in either primary or
      secondary cell wall biosynthesis.

PMID- 16452069
TI  - Assessment of Populus wood chemistry following the introduction of a Bt toxin
      gene.
AB  - Unintended changes in plant physiology, anatomy and metabolism as a result of
      genetic engineering are a concern as more transgenic plants are commercially
      deployed in the ecosystem. We compared the cell wall chemical composition of
      three Populus lines (Populus trichocarpa Torr. & A. Gray x Populus trichocarpa
      Bartr. ex Marsh., Populus trichocarpa x Populus nigra L. and Populus deltoides x
      Populus nigra) genetically modified to express the Cry3A or Cry3B2 protein of
      Bacillus thuringiensis (Bt) with the cell wall chemistry of non-transformed
      isogenic control lines. Three genetically modified clones, each represented by 10
      independent transgenic lines, were analyzed by pyrolysis molecular beam mass
      spectrometry, gas chromatography/mass spectrometry and traditional wet chemical
      analytical methods to assess changes in cell wall composition. Based on the
      outcome of these techniques, there were no comprehensive differences in chemical
      composition between the transgenic and control lines for any of the studied
      clones.

PMID- 16452070
TI  - Citrate-release-mediated aluminum resistance is coupled to the inducible
      expression of mitochondrial citrate synthase gene in Paraserianthes falcataria.
AB  - Aluminum (Al) resistance in some leguminous plants is achieved by enhanced
      citrate release from roots. Enhancement requires several hours for complete
      activation and is postulated to involve Al-responsive genes or components. We
      examined the mechanism of Al-induced citrate release by studying the relationship
      between citrate release and expression of the mitochondrial citrate synthase
      (mCS) gene in three leguminous trees. Root elongation in Leucaena leucocephala
      (Lam.) de Wit was arrested within 24 h by 30 microM Al, whereas root elongation
      in Paraserianthes falcataria (L.) Neilson and Acacia mangium Willd. was inhibited
      < 50% by a 48-h treatment with 100 microM Al in calcium chloride solution. Roots
      of P. falcataria and A. mangium maintained enhanced release and accumulation of
      citrate for at least 28 days in response to Al treatment. Aluminum increased the
      accumulation of mCS transcripts in P. falcataria roots, but not in L.
      leucocephala roots, and thus up-regulation decreased following removal of Al.
      Lanthanum did not alter the expression level of mCS. Aluminum increased mCS
      activity concomitantly with enhanced mCS gene expression in P. falcataria,
      whereas it did not affect mCS activity in L. leucocephala. Aluminum content in
      root apices of P. falcataria was increased by cycloheximide, supporting the idea
      that de novo synthesis of proteins is a prerequisite for Al resistance. Our
      findings suggest that Al-inducible expression of mCS coupled with enhanced
      citrate release mediates Al resistance in P. falcataria.

PMID- 16452071
TI  - Differential regulation of two dehydrin genes from peach (Prunus persica) by
      photoperiod, low temperature and water deficit.
AB  - Dehydrins are one of several proteins that have been specifically associated with
      qualitative and quantitative changes in cold hardiness. Recent evidence indicates
      that the regulation of dehydrin genes by low nonfreezing temperature (LT) and
      short photoperiod (SD) can be complex and deserves more detailed analysis to
      better understand the role of specific dehydrin genes and proteins in the
      response of woody plants to environmental stress. We have identified a new peach
      (Prunus persica (L.) Batsch) dehydrin gene (PpDhn2) and examined the responses of
      this gene and a previously identified dehydrin (PpDhn1) to SD, LT and water
      deficit. PpDhn2 was strongly induced by water deficit but not by LT or SD. It was
      also present in the mature embryos of peach. In contrast, PpDhn1 was induced by
      water deficit and LT but not by SD. We conducted an in silico analysis of the
      promoters of these genes and found that the promoter region of PpDhn1 contained
      two dehydration-responsive-elements (DRE)/C-repeats that are responsive to LT and
      several abscisic acid (ABA)-response elements (ABREs). In contrast, the promoter
      region of PpDhn2 contained no LT elements but contained several ABREs and an
      MYCERD1 motif. Both promoter analyses were consistent with the observed
      expression patterns. The discrepancy between field-collected samples and growth
      chamber experiments in the expression of PpDhn1 in response to SD suggests that
      SD-induced expression of dehydrin genes is complex and may be the result of
      several interacting factors.

PMID- 16452072
TI  - Somaclonal variation in micropropagated oil palm. Characterization of two novel
      genes with enhanced expression in epigenetically abnormal cell lines and in
      response to auxin.
AB  - In vitro micropropagation based on somatic embryogenesis provides an efficient
      means to multiply selected genotypes of oil palm (Elaeis guineensis Jacq.).
      Despite its considerable potential, somatic embryogenesis can yield plants
      bearing a homeotic flowering abnormality known as mantled. Because the mantled
      abnormality is epigenetic, it cannot be detected with conventional structural
      molecular markers. Thus, to develop a means of discriminating among callus
      cultures carrying or lacking the mantled abnormality, we used a gene expression
      approach. We describe two novel oil palm genes, EgM39A and EgIAA1, both of which
      display increased transcript accumulation in epigenetically abnormal calli.
      EgIAA1 codes for an oil palm relative of the Arabidopsis thaliana (L.) Heynh.
      AXR3/IAA17 protein involved in early auxin response and EgM39A codes for a
      protein of unknown function sharing sequence similarities with asparagine
      synthetases. In addition to their enhanced expression in somaclonal variant
      callus lines, both genes displayed increased transcript accumulation in response
      to auxin treatment. Normal seed-derived zygotic embryos germinated in the
      presence of auxin accumulated increased amounts of EgIAA1 transcripts after a few
      hours of treatment, suggesting a role in auxin response similar to that
      demonstrated for IAA genes in other species. The EgM39A gene also displayed
      enhanced transcript accumulation in auxin-treated zygotic embryos. Although only
      a small increase was seen after 24 h, greater changes were observed after 15
      days. Both genes show potential as early markers of clonal conformity and may
      help to elucidate the nature of the epigenetic changes causing the mantled
      abnormality.

PMID- 16452073
TI  - Phenotypic variation and quantitative trait locus identification for osmotic
      potential in an interspecific hybrid inbred F2 poplar pedigree grown in
      contrasting environments.
AB  - Elucidation of the mechanisms of dehydration tolerance in poplar (Populus sp.)
      trees will permit development of biochemical and molecular indicators to identify
      dehydration-tolerant genotypes during genetic selection. The objectives of this
      study were to characterize the degree of phenotypic variation in osmotic
      potential (a determinant of dehydration tolerance), determine the relationship
      between osmotic potential at full turgor and relative growth rate, and identify
      quantitative trait loci (QTL) for osmotic potential in an advanced-generation,
      interspecific poplar pedigree established in contrasting environments. A three
      generation, sib-mated black cottonwood (Populus trichocarpa Torr. & Gray) and
      eastern cottonwood (P. deltoides Bartr.) segregating F(2) family (Family 331) was
      analyzed at a dry site east of the Cascade Mountain Range (Boardman, OR) and at a
      wet site west of the mountains (Clatskanie, OR). At the Boardman site, 2-year-old
      trees (59 clones) were either irrigated everyday (wet) or every other day (dry),
      whereas 3- and 4-year-old trees (58 clones) at the Clatskanie site were
      unirrigated. At the Boardman site, the typically narrow range of osmotic
      potentials exhibited by grandparents and parents was greatly expanded in the F(2)
      population, spanning from -1.38 to -2.35 MPa under wet conditions, with a similar
      range under dry conditions (-1.40 to -2.15 MPa). Clones that had osmotic
      potentials < or = -1.90 MPa generally displayed full maintenance of stem relative
      growth rates under dry conditions in contrast to clones with osmotic potentials
      that were < or = -1.60 MPa, in which stem relative growth rates were reduced by
      an average of 38% in the dry treatment relative to the wet treatment. Although
      osmotic adjustments of 0.13 to 0.36 MPa were observed in nine out of 59 clones,
      adjustment typically occurred from relatively high baseline osmotic potentials.
      The range in osmotic potential at the wetter Clatskanie site at age three was
      higher (-1.27 to -1.84 MPa) and was further expanded the following year (-1.14 to
      -1.94 MPa), which had a wetter spring than the previous year, followed by a
      typically dry July. Seven QTL for osmotic potential were identified that each
      explained > 7.5% of the variation in osmotic potential. Given that four clones
      (7%) had osmotic potentials of -2.00 MPa or less and that QTL for osmotic
      potential have been identified, we suggest that there are opportunities to extend
      the limit of dehydration tolerance in Populus.

PMID- 16452075
TI  - The importance of being red when young: anthocyanins and the protection of young
      leaves of Quercus coccifera from insect herbivory and excess light.
AB  - Young leaves of many plants are transiently red because of the accumulation of
      anthocyanins, with the redness disappearing as leaves mature. Among the many
      hypothetical functions of foliar anthocyanins, two are tested in this field
      study: the sunscreen photoprotective function against excess visible light and
      the handicap signal against herbivory. We took advantage of intraspecies
      variation in anthocyanin concentrations of young leaves of Quercus coccifera L.
      to compare in vivo chlorophyll fluorescence parameters, reflectance spectra,
      total phenolics and the extent of herbivory of leaves of red- and green-leaved
      phenotypes occupying the same habitat. Photosystem II (PSII) photochemical
      efficiencies obtained at various photon fluence rates of red light were similar
      in green and red leaves. In white light, PSII efficiencies were slightly higher
      in red leaves than in green leaves, indicating a slight photoprotective role of
      anthocyanins in the field. However, compared with red phenotypes, green
      phenotypes suffered greater herbivore damage, as judged by the number of leaves
      attacked and the area lost to herbivory. In addition, there was a positive
      correlation between the concentrations of anthocyanins and total phenolics. We
      suggest that the importance of a photoprotective anthocyanic screen is low in
      thin, young leaves with low chlorophyll concentrations because the green light
      attenuated by anthocyanins is less significant for chlorophyll excitation.
      However, the decreased reflectance in the green spectral band and the concomitant
      leveling of reflectance throughout the 400-570 nm spectral range may either make
      red leaves less discernible to some insect herbivores or make insect herbivores
      more discernible to predators, or both. Moreover, excessive herbivory may be
      additionally discouraged by the high phenolic concentrations in red leaves.

PMID- 16452074
TI  - Monolignol oxidation by xylem peroxidase isoforms of Norway spruce (Picea abies)
      and silver birch (Betula pendula).
AB  - We partially purified peroxidase isoform fractions from xylem extracts of a
      gymnosperm, Norway spruce (Picea abies (L.) Karst.), and an angiosperm, silver
      birch (Betula pendula Roth.), to determine the participation of xylem-localized
      peroxidases in polymerization of different types of lignin in vivo. Several
      peroxidase fractions varying in isoelectric point values from acidic to basic
      were tested for their ability to catalyze the oxidation of the monolignols
      coniferyl alcohol, sinapyl alcohol and p-coumaryl alcohol in vitro. All of the
      xylem peroxidases extracted from Norway spruce and most of those from silver
      birch showed the highest rate of oxidation with coniferyl alcohol in the presence
      of hydrogen peroxide. The exception was an acidic peroxidase fraction (pI 3.60
      3.65) from silver birch that exhibited higher oxidation activity for sinapyl
      alcohol than for coniferyl alcohol. For the xylem enzyme fractions extracted from
      silver birch, the ability to oxidize the artificial phenolic substrate
      syringaldazine coincided with high specific activity for sinapyl alcohol.
      Therefore, we conclude that the acidic, neutral and basic xylem peroxidases of
      Norway spruce all function in the synthesis of guaiacyl-type lignin, whereas in
      silver birch the acidic peroxidases preferentially oxidize sinapyl subunits. The
      latter provides a mechanism for synthesis of guaiacyl-syringyl lignin typical of
      tracheid cell walls in angiosperm trees.

PMID- 16452077
TI  - Coordination of crown structure, leaf plasticity and carbon gain within the
      crowns of three winter-deciduous mature trees.
AB  - We examined the vertical profiles of leaf characteristics within the crowns of
      two late-successional (Fagus crenata Blume and Fagus japonica Maxim.) and one
      early-successional tree species (Betula grossa Sieb. et Zucc.) in a Japanese
      forest. We also assessed the contributions of the leaves in each crown layer to
      whole-crown instantaneous carbon gain at midday. Carbon gain was estimated from
      the relationship between electron transport and photosynthetic rates. We
      hypothesized that more irradiance can penetrate into the middle of the crown if
      the upper crown layers have steep leaf inclination angles. We found that such a
      crown has a high whole-crown carbon gain, even if leaf traits do not change
      greatly with decreasing crown height. Leaf area indices (LAIs) of the two Fagus
      trees (5.26-5.52) were higher than the LAI of the B. grossa tree (4.50) and the
      leaves of the F. crenata tree were more concentrated in the top crown layers than
      were leaves of the other trees. Whole-crown carbon gain per unit ground area
      (micromol m(-2) ground s(-1)) at midday on fine days in summer was 16.3 for F.
      crenata, 11.0 for F. japonica, and 20.4 for B. grossa. In all study trees, leaf
      dry mass (LMA) and leaf nitrogen content (N) per unit area decreased with
      decreasing height in the crown, but leaf N per unit mass increased. Variations
      (plasticity) between the uppermost and lowermost crown layers in LMA, leaf N, the
      ratio of chlorophyll to N and the ratio of chlorophyll a to b were smaller for F.
      japonica and B. grossa than for F. crenata. The light extinction coefficients in
      the crowns were lower for the F. japonica and B. grossa trees than for the F.
      crenata tree. The leaf carbon isotope ratio (delta(13)C) was higher for F.
      japonica and B. grossa than for F. crenata, especially in the mid-crown. These
      results suggest that, in crowns with low leaf plasticity but steep leaf
      inclination angles, such as those of F. japonica and B. grossa trees, irradiance
      can penetrate into the middle of the crowns, thereby enhancing whole-crown carbon
      gain.

PMID- 16452076
TI  - Patterns of shoot mortality in Betula platyphylla in northern Japan.
AB  - To understand the development of crown structure in Betula platyphylla Sukatch.,
      mortality patterns of long shoots were analyzed quantitatively. We selected 25
      saplings growing under various light conditions and measured the relative
      photosynthetically active radiation (rPAR) at, and the three-dimensional position
      of, first-order branches. A long shoot was assigned "no buds" (NB) status if it
      lacked buds at the end of the growing season, including at the tips of short
      shoots. A long shoot was classified as dead if it was NB and all the offspring
      long shoots issuing from it were NB. The probability that a leafy long shoot (a
      current-year long shoot with leaves or an older long shoot with short shoots with
      leaves) would become NB by the end of the season was positively dependent on
      shoot age and branch age, and negatively dependent on shoot length, centripetal
      shoot order, branch height and rPAR at the branch. Randomization tests revealed
      that shoots became NB and dead in clusters of connected shoots. In particular,
      shoot clusters originating from 3-year-old shoots were more likely to die than
      expected if each shoot was assumed to become NB regardless of the connection.
      Stepwise logistic regression revealed that the maximum rPAR within the crown of
      an individual tree had a significant effect on the mortality rate of 3-year-old
      shoot clusters, together with the rPAR at the level of the branch and other
      structural entities. Correlative inhibition is an important mechanism for
      determining shoot mortality patterns.

PMID- 16452078
TI  - Contrasting seasonal leaf habits of canopy trees between tropical dry-deciduous
      and evergreen forests in Thailand.
AB  - We compared differences in leaf properties, leaf gas exchange and photochemical
      properties between drought-deciduous and evergreen trees in tropical dry forests,
      where soil nutrients differed but rainfall was similar. Three canopy trees
      (Shorea siamensis Miq., Xylia xylocarpa (Roxb.) W. Theob. and Vitex peduncularis
      Wall. ex Schauer) in a drought-deciduous forest and a canopy tree (Hopea ferrea
      Lanessan) in an evergreen forest were selected. Soil nutrient availability is
      lower in the evergreen forest than in the deciduous forest. Compared with the
      evergreen tree, the deciduous trees had shorter leaf life spans, lower leaf
      masses per area, higher leaf mass-based nitrogen (N) contents, higher leaf mass
      based photosynthetic rates (mass-based P(n)), higher leaf N-based P(n), higher
      daily maximum stomatal conductance (g(s)) and wider conduits in wood xylem. Mass
      based P(n) decreased from the wet to the dry season for all species. Following
      onset of the dry season, daily maximum g(s) and sensitivity of g(s) to leaf-to
      air vapor pressure deficit remained relatively unchanged in the deciduous trees,
      whereas both properties decreased in the evergreen tree during the dry season.
      Photochemical capacity and non-photochemical quenching (NPQ) of photosystem II
      (PSII) also remained relatively unchanged in the deciduous trees even after the
      onset of the dry season. In contrast, photochemical capacity decreased and NPQ
      increased in the evergreen tree during the dry season, indicating that the leaves
      coped with prolonged drought by down-regulating PSII. Thus, the drought-avoidant
      deciduous species were characterized by high N allocation for leaf carbon
      assimilation, high water use and photoinhibition avoidance, whereas the drought
      tolerant evergreen was characterized by low N allocation for leaf carbon
      assimilation, conservative water use and photoinhibition tolerance.

PMID- 16452079
TI  - Seasonal patterns of leaf gas exchange and water relations in dry rain forest
      trees of contrasting leaf phenology.
AB  - Diurnal and seasonal patterns of leaf gas exchange and water relations were
      examined in tree species of contrasting leaf phenology growing in a seasonally
      dry tropical rain forest in north-eastern Australia. Two drought-deciduous
      species, Brachychiton australis (Schott and Endl.) A. Terracc. and Cochlospermum
      gillivraei Benth., and two evergreen species, Alphitonia excelsa (Fenzal) Benth.
      and Austromyrtus bidwillii (Benth.) Burret. were studied. The deciduous species
      had higher specific leaf areas and maximum photosynthetic rates per leaf dry mass
      in the wet season than the evergreens. During the transition from wet season to
      dry season, total canopy area was reduced by 70-90% in the deciduous species and
      stomatal conductance (g(s)) and assimilation rate (A) were markedly lower in the
      remaining leaves. Deciduous species maintained daytime leaf water potentials
      (Psi(L)) at close to or above wet season values by a combination of stomatal
      regulation and reduction in leaf area. Thus, the timing of leaf drop in deciduous
      species was not associated with large negative values of daytime Psi(L) (greater
      than -1.6 MPa) or predawn Psi(L) (greater than -1.0 MPa). The deciduous species
      appeared sensitive to small perturbations in soil and leaf water status that
      signalled the onset of drought. The evergreen species were less sensitive to the
      onset of drought and g(s) values were not significantly lower during the
      transitional period. In the dry season, the evergreen species maintained their
      canopies despite increasing water-stress; however, unlike Eucalyptus species from
      northern Australian savannas, A and g(s) were significantly lower than wet season
      values.

PMID- 16452081
TI  - Internal cycling of nitrogen, potassium and magnesium in young Sitka spruce.
AB  - Potassium (K) and magnesium (Mg) are essential macro-nutrients, but little is
      known about how they are cycled within plants. Stable isotope studies have shown
      that the internal cycling of nitrogen (N) is independent of current nutrient
      supply in temperate tree species. This is ecologically significant because it
      allows trees to produce rapid shoot growth in spring independent of current soil
      N uptake. We used stable isotopes to quantify N, K and Mg in new shoots of Sitka
      spruce (Picea sitchensis (Bong.) Carr.) seedlings and to compare the relative
      contributions from current uptake and internal cycling. Two-year-old Sitka spruce
      seedlings were labeled with (15)N, (41)K and (26)Mg in an abundant or a limited
      supply for one growing season. The trees were repotted in the subsequent dormant
      season to prevent further root uptake of enriched isotopes and provided with an
      abundant or a limited supply of unlabeled nutrients until they were harvested in
      early summer of the following year. The supply was switched for half the trees in
      the second year to create four nutrient regimes. Enrichment of (15)N, (41)K and
      (26)Mg in current-year growth was attributed to internally cycled N, K and Mg
      uptake from the previous year. The internal cycling of N, K and Mg in new growth
      was significantly affected by the first-year nutrient treatments. The second-year
      nutrient supply affected the growth rates of the trees, but had no effect on the
      amounts of N, K or Mg contributed from internal cycling. Thus, internal cycling
      of K and Mg in Sitka spruce are, like that of N, independent of current nutrient
      supply.

PMID- 16452080
TI  - Growth and physiological responses to supplemental UV-B radiation of two
      contrasting poplar species.
AB  - We compared the growth and physiological responses of cuttings of Populus
      kangdingensis C. Wang et Tung and P. cathayana Rehder originating from altitudes
      of 3500 m and 1500 m, respectively, when exposed to three ultraviolet-B (UV-B)
      radiation regimes: zero UV-B, ambient (4.5 kJ m(-2) day(-1)) and twice-ambient (9
      kJ m(-2) day(-1)) biologically effective UV-B radiation for one growing season,
      to determine if Populus trees that are adapted to contrasting UV-B habitats
      exhibit different tolerances to enhanced UV-B radiation. Compared with cuttings
      grown without UV-B radiation, twice-ambient UV-B radiation significantly
      decreased total biomass, total leaf area and internode length in both species,
      whereas root/shoot ratio, leaf number, amount of photosynthetic pigments and
      ascorbate peroxidase activity were unaffected. Differences in responses were also
      observed between the study species. Cutting height increment, total biomass,
      total leaf area, free proline concentration and membrane damage assessed by
      electrolyte leakage were significantly more affected by the twice-ambient UV-B
      radiation in P. cathayana than in P. kangdingensis. However, specific leaf mass,
      amount of UV-B absorbing compounds and superoxide dismutase and guaiacol
      peroxidase activities increased more with increasing UV-B radiation in P.
      kangdingensis than in P. cathayana, perhaps reflecting important characteristics
      of species with low to moderate tolerance to UV-B radiation. Overall, the results
      indicated that P. kangdingensis, which originates from altitudes of 3500 m, has
      greater tolerance to enhanced UV-B radiation than P. cathayana originating from
      altitudes of 1500 m.

PMID- 16452082
TI  - Signals controlling root suckering and adventitious shoot formation in aspen
      (Populus tremuloides).
AB  - We determined the effects of removal of leaves, stem axillary buds, or the entire
      shoot on root suckering (adventitious shoot formation by roots) and basal stem
      sprouts in 3- and 4-year-old potted seedlings of aspen (Populus tremuloides
      Michx.). The greatest number of root suckers (67.9 +/- 8.5 per plant) emerged
      after excision of the entire shoot. Defoliated and debudded stems were the major
      source of inhibitory agents for root suckering, although axillary buds and
      developing new leaves also exerted a significant inhibitory effect. Removal of
      mature leaves had only a minor effect on root suckering. Removal of a continuous
      band of bark (girdling) at the base of the stem consistently stimulated growth of
      adventitious shoots from the stem below the girdle and occasionally promoted root
      suckering. Exogenous application of indole-3-acetic acid to excised stumps
      inhibited root suckering and basal stem sprouting. Naphthylphthalamic acid (NPA),
      an auxin polar transport inhibitor, had no effect on root suckering or stem
      sprouting when it was applied to the bark of the basal stem. However, NPA
      significantly increased root suckering when it was applied to the exposed surface
      of xylem after girdling. These results suggest that polar transport of auxin in
      the xylem parenchyma is an important inhibitor of root suckering. On decapitated
      stems, vacuum extraction of xylem sap from the root system lowered the frequency
      of root suckering compared with decapitation alone, indicating that substance(s)
      originating in the root system also play a significant role in controlling root
      suckering.

PMID- 16452083
TI  - Clinical pharmacy practice--its functional relationship to drug information
      service. 1971.

PMID- 16452084
TI  - Education and training of the drug information specialist. 1967.

PMID- 16452085
TI  - Combinations of antibiotics. 1968.

PMID- 16452086
TI  - Patient oriented pharmacy practice--does it include traditional services? 1975.

PMID- 16452087
TI  - Comprehensive identification of phosphorylation sites in postsynaptic density
      preparations.
AB  - In the mammalian central nervous system, the structure known as the postsynaptic
      density (PSD) is a dense complex of proteins whose function is to detect and
      respond to neurotransmitter released from presynaptic axon terminals. Regulation
      of protein phosphorylation in this molecular machinery is critical to the
      activity of its components, which include neurotransmitter receptors,
      kinases/phosphatases, scaffolding molecules, and proteins regulating cytoskeletal
      structure. To characterize the phosphorylation state of proteins in PSD samples,
      we combined strong cation exchange (SCX) chromatography with IMAC. Initially,
      tryptic peptides were separated by cation exchange and analyzed by reverse phase
      chromatography coupled to tandem mass spectrometry, which led to the
      identification of phosphopeptides in most SCX fractions. Because each of these
      individual fractions was too complex to characterize completely in single LC
      MS/MS runs, we enriched for phosphopeptides by performing IMAC on each SCX
      fraction, yielding at least a 3-fold increase in identified phosphopeptides
      relative to either approach alone (SCX or IMAC). This enabled us to identify at
      least one site of phosphorylation on 23% (287 of 1,264) of all proteins found to
      be present in the postsynaptic density preparation. In total, we identified 998
      unique phosphorylated peptides, mapping to 723 unique sites of phosphorylation.
      At least one exact site of phosphorylation was determined on 62% (621 of 998) of
      all phosphopeptides, and approximately 80% of identified phosphorylation sites
      are novel.

PMID- 16452088
TI  - O-linked N-acetylglucosamine proteomics of postsynaptic density preparations
      using lectin weak affinity chromatography and mass spectrometry.
AB  - O-GlcNAc is a widespread dynamic carbohydrate modification of cytosolic and
      nuclear proteins with features analogous to phosphorylation. O-GlcNAc acts
      critically in many cellular processes, including signal transduction, protein
      degradation, and regulation of gene expression. However, the study of its
      specific regulatory functions has been limited by difficulties in mapping sites
      of O-GlcNAc modification. We report methods for direct enrichment and
      identification of in vivo O-GlcNAc-modified peptides through lectin weak affinity
      chromatography (LWAC) and mass spectrometry. The effectiveness of this strategy
      on complex peptide mixtures was demonstrated through enrichment of 145 unique O
      GlcNAc-modified peptides from a postsynaptic density preparation. 65 of these O
      GlcNAc-modified peptides were sequenced and belonged to proteins with diverse
      functions in synaptic transmission. Beta-elimination/Michael addition, MS(3) on O
      GlcNAc neutral loss ions, and electron capture dissociation were shown to
      facilitate analysis of O-GlcNAc-modified peptides/sites from lectin weak affinity
      chromatography enriched postsynaptic density samples. Bassoon and Piccolo,
      proteins critical to synapse assembly and vesicle docking, were extensively
      modified by O-GlcNAc. In some cases, O-GlcNAc was mapped to peptides previously
      identified as phosphorylated, indicating potential interplay between these
      modifications. Shared substrate amino acid context was apparent in subsets of O
      GlcNAc-modified peptides, including "PVST" and a novel "TTA" motif (two hydroxyl
      containing amino acids adjacent to an alanine). The results suggest specific
      roles for O-GlcNAc modification in synaptic transmission, establish a basis for
      site-specific regulatory studies, and provide methods that will facilitate O
      GlcNAc proteome analysis across a wide variety of cells and tissues.

PMID- 16452089
TI  - Proteomic profiling of accessory structures from the mouse sperm flagellum.
AB  - The flagellum of a mammalian spermatozoon consists of an axoneme surrounded in
      distinct regions by accessory structures known as the fibrous sheath, outer dense
      fibers, and the mitochondrial sheath. Although the characterization of individual
      proteins has provided clues about the roles of these accessory structures, a more
      complete understanding of flagellar function requires the identification of all
      the polypeptides in these assemblies. Epididymal mouse sperm were treated with
      SDS to dislodge sperm heads and to extract the axoneme and membranous elements.
      The remaining flagellar accessory structures were purified by sucrose gradient
      centrifugation. Analysis of proteins from these structures by two-dimensional gel
      electrophoresis and colloidal Coomassie Blue staining showed a highly
      reproducible pattern of >200 spots. Individual spots were picked, digested with
      trypsin, and identified by mass spectrometry and peptide microsequencing.
      Approximately 50 individual proteins were identified that could be assigned to
      five general categories: 1) proteins previously reported to localize to the
      accessory structures, e.g. ODF2 in the outer dense fibers, the sperm-specific
      glyceraldehyde-3-phosphate dehydrogenase in the fibrous sheath, and glutathione
      peroxidase in the mitochondrial sheath, validating this proteomic approach; 2)
      proteins that had not been shown to localize to any accessory structure but would
      be predicted to be present, e.g. glycolytic enzymes; 3) proteins known to be part
      of the flagellum but not localized to a specific site, e.g. adenylate kinase; 4)
      proteins not expected to be part of the accessory structures based on their
      previously reported locations, e.g. tektins; and 5) unknown proteins for which no
      information is available to make a determination as to location. The unexpected
      presence of the tektins in the accessory structures of the flagellum was
      confirmed by both immunoblot and immunofluorescence analysis. This proteomic
      analysis identified a number of unexpected and novel proteins in the accessory
      structures of the mammalian flagellum.

PMID- 16452090
TI  - Competence of cranial ectoderm to respond to Fgf signaling suggests a two-step
      model of otic placode induction.
AB  - Vertebrate craniofacial sensory organs derive from ectodermal placodes early in
      development. It has been suggested that all craniofacial placodes arise from a
      common ectodermal domain adjacent to the anterior neural plate, and a number of
      genes have been recently identified that mark such a 'pre-placodal' domain.
      However, the functional significance of this pre-placodal domain is still
      unclear. In the present study, we show that Fgf signaling is necessary and
      sufficient to directly induce some, but not all, markers of the otic placode in
      ectoderm taken from the pre-placodal domain. By contrast, ectoderm from outside
      this domain is not competent to express otic markers in response to Fgfs.
      Grafting naive ectoderm into the pre-placodal domain causes upregulation of pre
      placodal markers within 8 hours, together with the acquisition of competence to
      respond to Fgf signaling. This suggests a two-step model of craniofacial placode
      induction in which ectoderm first acquires pre-placodal region identity, and
      subsequently differentiates into particular craniofacial placodes under the
      influence of local inducing signals.

PMID- 16452091
TI  - An ancient Wnt-Dickkopf antagonism in Hydra.
AB  - The dickkopf (dkk) gene family encodes secreted antagonists of Wnt signalling
      proteins, which have important functions in the control of cell fate,
      proliferation, and cell polarity during development. Here, we report the
      isolation, from a regeneration-specific signal peptide screen, of a novel
      dickkopf gene from the fresh water cnidarian Hydra. Comparative sequence analysis
      demonstrates that the Wnt antagonistic subfamily Dkk1/Dkk2/Dkk4 and the non
      modulating subfamily Dkk3 separated prior to the divergence of cnidarians and
      bilaterians. In steady-state Hydra, hydkk1/2/4-expression is inversely related to
      that of hywnt3a. hydkk1/2/4 is an early injury and regeneration responsive gene,
      and hydkk1/2/4-expressing gland cells are essential for head regeneration in
      Hydra, although once the head has regenerated they are excluded from it.
      Activation of Wnt/beta-Catenin signalling leads to the complete downregulation of
      hydkk1/2/4 transcripts. When overexpressed in Xenopus, HyDkk1/2/4 has similar Wnt
      antagonizing activity to the Xenopus gene Dkk1. Based on the corresponding
      expression patterns of hydkk1/2/4 and neuronal genes, we suggest that the body
      column of Hydra is a neurogenic environment suppressing Wnt signalling and
      facilitating neurogenesis.

PMID- 16452092
TI  - Inactivation of Tbx1 in the pharyngeal endoderm results in 22q11DS malformations.
AB  - The 22q11 deletion (22q11DS; velo-cardio-facial syndrome/DiGeorge syndrome) is
      characterized by defects in the derivatives of the pharyngeal apparatus. Mouse
      genetic studies have identified Tbx1, a member of the T-box family of
      transcription factors, as being responsible for the physical malformations of the
      syndrome. Mice heterozygous for a null mutation in Tbx1 have mild anomalies,
      whereas homozygous Tbx1 mutants die at birth with severe defects in the
      derivatives of the pharyngeal apparatus, including cleft palate, thymus gland
      aplasia and cardiac outflow tract malformations. Tbx1 is expressed in the
      splanchnic mesenchyme, the pharyngeal endoderm (PE) and in the core mesoderm of
      the pharyngeal apparatus. Tissue interactions between the epithelia and
      mesenchyme of the arches are required for development of the pharyngeal
      apparatus; the precise role of Tbx1 in each tissue is not known. To assess the
      role of Tbx1 in the PE, a conditional allele of Tbx1 was generated using the
      Cre/loxP system. Foxg1-Cre was used to drive PE-specific ablation of Tbx1.
      Conditional null mutants survived embryogenesis, but died in the neonatal period
      with malformations identical to the defects observed in Tbx1 homozygous null
      mutants. The abnormalities appear to be secondary to failed outgrowth of the
      pharyngeal pouches. These results show that Tbx1 in the PE is required for the
      patterning and development of the pharyngeal apparatus, thereby disrupting the
      formation of its derivative structures.

PMID- 16452093
TI  - Retinoids signal directly to zebrafish endoderm to specify insulin-expressing
      beta-cells.
AB  - During vertebrate development, the endodermal germ layer becomes regionalized
      along its anteroposterior axis to give rise to a variety of organs, including the
      pancreas. Genetic studies in zebrafish and mice have established that the
      signaling molecule retinoic acid (RA) plays a crucial role in endoderm patterning
      and promotes pancreas development. To identify how RA signals to pancreatic
      progenitors in the endoderm, we have developed a novel cell transplantation
      technique, using the ability of the SOX32 transcription factor to confer
      endodermal identity, to selectively target reagents to (or exclude them from) the
      endodermal germ layer of the zebrafish. We show that RA synthesized in the
      anterior paraxial mesoderm adjacent to the foregut is necessary for the
      development of insulin-expressing beta-cells. Conversely, RA receptor function is
      required in the foregut endoderm for insulin expression, but not in mesoderm or
      ectoderm. We further show that activation of RA signal transduction in endoderm
      alone is sufficient to induce insulin expression. Our results reveal that RA is
      an instructive signal from the mesoderm that directly induces precursors of the
      endocrine pancreas. These findings suggest that RA will have important
      applications in the quest to induce islets from stem cells for therapeutic uses.

PMID- 16452094
TI  - Signal dynamics in Sonic hedgehog tissue patterning.
AB  - During development, secreted signaling factors, called morphogens, instruct cells
      to adopt specific mature phenotypes. However, the mechanisms that morphogen
      systems employ to establish a precise concentration gradient for patterning
      tissue architecture are highly complex and are typically analyzed only at long
      times after secretion (i.e. steady state). We have developed a theoretical model
      that analyzes dynamically how the intricate transport and signal transduction
      mechanisms of a model morphogen, Sonic hedgehog (Shh), cooperate in modular
      fashion to regulate tissue patterning in the neural tube. Consistent with
      numerous recent studies, the model elucidates how the dynamics of gradient
      formation can be a key determinant of cell response. In addition, this work
      yields several novel insights into how different transport mechanisms or
      ;modules' control pattern formation. The model predicts that slowing the
      transport of a morphogen, such as by lipid modification of the ligand Shh, by
      ligand binding to proteoglycans, or by the moderate upregulation of dedicated
      transport molecules like Dispatched, can actually increase the signaling range of
      the morphogen by concentrating it near the secretion source. Furthermore, several
      transcriptional targets of Shh, such as Patched and Hedgehog-interacting protein,
      significantly limit its signaling range by slowing transport and promoting ligand
      degradation. This modeling approach elucidates how individual modular elements
      that operate dynamically at various times during patterning can shape a tissue
      pattern.

PMID- 16452095
TI  - Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning
      of the zebrafish diencephalon.
AB  - Midway between the anterior neural border and the midbrain-hindbrain boundary,
      two well-known local signalling centres in the early developing brain, is a
      further transverse boundary with putative signalling properties -- the zona
      limitans intrathalamica (ZLI). Here, we describe formation of the ZLI in
      zebrafish in relation to expression of sonic hedgehog (shh) and tiggy-winkle
      hedgehog (twhh), and to development of the forebrain regions that flank the ZLI:
      the prethalamus and thalamus. We find that enhanced Hh signalling increases the
      size of prethalamic and thalamic gene expression domains, whereas lack of Hh
      signalling leads to absence of these domains. In addition, we show that shh and
      twhh display both unique and redundant functions during diencephalic patterning.
      Genetic ablation of the basal plate shows that Hh expression in the ZLI alone is
      sufficient for diencephalic differentiation. Furthermore, acquisition of correct
      prethalamic and thalamic gene expression is dependent on direct Hh signalling. We
      conclude that proper maturation of the diencephalon requires ZLI-derived Hh
      signalling.

PMID- 16452096
TI  - Notch 1 inhibits photoreceptor production in the developing mammalian retina.
AB  - The transmembrane receptor Notch1 plays a role in development and homeostasis in
      vertebrates and invertebrates. The mammalian retina is an excellent tissue in
      which to dissect the precise role of Notch signaling in regulating cell fate and
      proliferation. However, a systematic analysis has been limited by the early
      embryonic lethality of Notch1-null mice. Here, Notch1 was conditionally removed
      from the murine retina either early or late in development. Removal of Notch1
      early led to a reduction in the size of the retina as well as aberrant
      morphology. A decrease in the number of progenitor cells and premature
      neurogenesis accounted for the reduction in size. Unexpectedly, ablation of
      Notch1 in early progenitor cells led to enhanced cone photoreceptor production,
      and ablation of Notch1 at later points led to an almost exclusive production of
      rod photoreceptor cells. These data suggest that Notch1 not only maintains the
      progenitor state, but is required to inhibit the photoreceptor fate. These cone
      enriched mutant mice should prove to be a valuable resource for the study of this
      relatively rare mammalian photoreceptor cell type.

PMID- 16452097
TI  - Fat and Wingless signaling oppositely regulate epithelial cell-cell adhesion and
      distal wing development in Drosophila.
AB  - Development of organ-specific size and shape demands tight coordination between
      tissue growth and cell-cell adhesion. Dynamic regulation of cell adhesion
      proteins thus plays an important role during organogenesis. In Drosophila, the
      homophilic cell adhesion protein DE-Cadherin (DE-Cad) regulates epithelial cell
      cell adhesion at adherens junctions (AJs). Here, we show that along the
      proximodistal (PD) axis of the developing wing epithelium, apical cell shapes and
      expression of DE-Cad are graded in response to Wingless (Wg), a morphogen
      secreted from the dorsoventral (DV) organizer in distal wing, suggesting a PD
      gradient of cell-cell adhesion. The Fat (Ft) tumor suppressor, by contrast,
      represses DE-Cad expression. In genetic tests, ft behaves as a suppressor of Wg
      signaling. Cytoplasmic pool of beta-catenin/Arm, the intracellular transducer of
      Wg signaling, is negatively correlated with the activity of Ft. Moreover, unlike
      that of Wg, signaling by Ft negatively regulates the expression of Distalless
      (Dll) and Vestigial (Vg). Finally, we show that Ft intersects Wnt/Wg signaling,
      downstream of the Wg ligand. Fat and Wg signaling thus exert opposing regulation
      to coordinate cell-cell adhesion and patterning along the PD axis of Drosophila
      wing.

PMID- 16452098
TI  - Wnt signals mediate a fate decision between otic placode and epidermis.
AB  - The otic placode, the anlagen of the inner ear, develops from an ectodermal field
      characterized by expression of the transcription factor Pax2. Previous fate
      mapping studies suggest that these Pax2(+) cells will give rise to both otic
      placode tissue and epidermis, but the signals that divide the Pax2(+) field into
      placodal and epidermal territories are unknown. We report that Wnt signaling is
      normally activated in a subset of Pax2(+) cells, and that conditional
      inactivation of beta-catenin in these cells causes an expansion of epidermal
      markers at the expense of the otic placode. Conversely, conditional activation of
      beta-catenin in Pax2(+) cells causes an expansion of the otic placode at the
      expense of epidermis, and the resulting otic tissue expresses exclusively dorsal
      otocyst markers. Together, these results suggest that Wnt signaling acts
      instructively to direct Pax2(+) cells to an otic placodal, rather than an
      epidermal, fate and promotes dorsal cell identities in the otocyst.

PMID- 16452100
TI  - Sema3a1 guides spinal motor axons in a cell- and stage-specific manner in
      zebrafish.
AB  - In order for axons to reach their proper targets, both spatiotemporal regulation
      of guidance molecules and stepwise control of growth cone sensitivity to guidance
      molecules is required. Here, we show that, in zebrafish, Sema3a1, a secreted
      class 3 semaphorin, plays an essential role in guiding the caudal primary (CaP)
      motor axon that pioneers the initial region of the motor pathway. The expression
      pattern of Sema3a1 suggests that it delimits the pioneer CaP axons to the
      initial, common pathway via a repulsive action, but then CaP axons become
      insensitive to Sema3a1 beyond the common pathway. Indeed, nrp1a, which probably
      encodes a component of the Sema3a1 receptor, is specifically expressed by CaP
      during the early part of its outgrowth but not during later stages when extending
      into sema3a1-expressing muscle cells. To examine this hypothesis directly,
      expression of sema3a1 and/or nrp1a was manipulated in several ways. First,
      antisense knockdown of Sema3a1 induced CaP axons to branch excessively, stall
      and/or follow aberrant pathways. Furthermore, dynamic analysis showed they
      extended more lateral filopodia and often failed to pause at the horizontal
      myoseptal choice point. Second, antisense knockdown of Nrp1a and double knockdown
      of Nrp1a/Sema3a1 induced similar outgrowth defects in CaP. Third, CaP axons were
      inhibited by focally misexpressed sema3a1 along the initial common pathway but
      not along their pathway beyond the common pathway. Thus, as predicted, Sema3a1 is
      repulsive to CaP axons in the common region of the pathway, but not beyond the
      common pathway. Fourth, induced ubiquitous overexpression of sema3a1 caused the
      CaP axons but not the other primary motor axons to follow aberrant pathways.
      These results suggest that the repulsive response to Sema3a1 of the primary motor
      axons along the common pathway is both cell-type specific and dynamically
      regulated, perhaps via regulation of nrp1a.

PMID- 16452099
TI  - Transgenic isolation of skeletal muscle and kidney defects in laminin beta2
      mutant mice: implications for Pierson syndrome.
AB  - Pierson syndrome is a recently defined disease usually lethal within the first
      postnatal months and caused by mutations in the gene encoding laminin beta2
      (LAMB2). The hallmarks of Pierson syndrome are congenital nephrotic syndrome
      accompanied by ocular abnormalities, including microcoria (small pupils), with
      muscular and neurological developmental defects also present. Lamb2(-/-) mice are
      a model for Pierson syndrome; they exhibit defects in the kidney glomerular
      barrier, in the development and organization of the neuromuscular junction, and
      in the retina. Lamb2(-/-) mice fail to thrive and die very small at 3 weeks of
      age, but to what extent the kidney and neuromuscular defects each contribute to
      this severe phenotype has been obscure, though highly relevant to understanding
      Pierson syndrome. To investigate this, we generated transgenic mouse lines
      expressing rat laminin beta2 either in muscle or in glomerular epithelial cells
      (podocytes) and crossed them onto the Lamb2(-/-) background. Rat beta2 was
      confined in skeletal muscle to synapses and myotendinous junctions, and in kidney
      to the glomerular basement membrane. In transgenic Lamb2(-/-) mice, beta2
      deposition in only glomeruli prevented proteinuria but did not ameliorate the
      severe phenotype. By contrast, beta2 expression in only muscle restored synaptic
      architecture and led to greatly improved health, but the mice died from kidney
      disease at 1 month. Rescue of both glomeruli and synapses was associated with
      normal weight gain, fertility and lifespan. We conclude that muscle defects in
      Lamb2(-/-) mice are responsible for the severe failure to thrive phenotype, and
      that renal replacement therapy alone will be an inadequate treatment for Pierson
      syndrome.

PMID- 16452101
TI  - EMERALD, AIMI, and PROMISE: is there still a potential for embolic protection in
      primary PCI?
AB  - The recent trials of routine use of embolic protection devices for primary
      percutaneous coronary interventions (PCI) (the EMERALD, PROMISE, and AIMI trials)
      have demonstrated neutral or even negative effects of these devices on myocardial
      reperfusion and final infarct size. Despite these results, there is still ground
      to believe that PCI-induced embolization may be clinically relevant in specific
      subsets of patients with acute myocardial infarction (AMI). Significant clinical
      consequences may be expected when embolization is quantitatively relevant and/or
      is qualitatively characterized by lipid-rich athero-embolism (as is the case of
      lipid core embolization through the ruptured cap of a fibro-atheroma). Future
      trials on embolic protection devices in primary PCI should adopt a selective,
      rather than a routine strategy, through the identification, by angiographic or
      intravascular imaging parameters, of patients at highest risk of clinically
      relevant embolization. Such trials should also adopt specific endpoints able to
      evaluate the effect of micro-embolization, which is currently far from optimally
      assessed by the standard markers of myocardial reperfusion.

PMID- 16452102
TI  - Non-degenerative mild cognitive impairment in elderly people and use of
      anticholinergic drugs: longitudinal cohort study.
AB  - OBJECTIVE: To assess the potential of anticholinergic drugs as a cause of non
      degenerative mild cognitive impairment in elderly people. DESIGN: Longitudinal
      cohort study. SETTING: 63 randomly selected general practices in the Montpellier
      region of southern France. PARTICIPANTS: 372 people aged > 60 years without
      dementia at recruitment. MAIN OUTCOME MEASURES: Anticholinergic burden from drug
      use, cognitive examination, and neurological assessment. RESULTS: 9.2% of
      subjects continuously used anticholinergic drugs during the year before cognitive
      assessment. Compared with non-users, they had poorer performance on reaction
      time, attention, delayed non-verbal memory, narrative recall, visuospatial
      construction, and language tasks but not on tasks of reasoning, immediate and
      delayed recall of wordlists, and implicit memory. Eighty per cent of the
      continuous users were classified as having mild cognitive impairment compared
      with 35% of non-users, and anticholinergic drug use was a strong predictor of
      mild cognitive impairment (odds ratio 5.12, P = 0.001). No difference was found
      between users and non-users in risk of developing dementia at follow-up after
      eight years. CONCLUSIONS: Elderly people taking anticholinergic drugs had
      significant deficits in cognitive functioning and were highly likely to be
      classified as mildly cognitively impaired, although not at increased risk for
      dementia. Doctors should assess current use of anticholinergic drugs in elderly
      people with mild cognitive impairment before considering administration of
      acetylcholinesterase inhibitors.

PMID- 16452103
TI  - Sham device v inert pill: randomised controlled trial of two placebo treatments.
AB  - OBJECTIVE: To investigate whether a sham device (a validated sham acupuncture
      needle) has a greater placebo effect than an inert pill in patients with
      persistent arm pain. DESIGN: A single blind randomised controlled trial created
      from the two week placebo run-in periods for two nested trials that compared
      acupuncture and amitriptyline with their respective placebo controls. Comparison
      of participants who remained on placebo continued beyond the run-in period to the
      end of the study. SETTING: Academic medical centre. PARTICIPANTS: 270 adults with
      arm pain due to repetitive use that had lasted at least three months despite
      treatment and who scored > or =3 on a 10 point pain scale. INTERVENTIONS:
      Acupuncture with sham device twice a week for six weeks or placebo pill once a
      day for eight weeks. MAIN OUTCOME MEASURES: Arm pain measured on a 10 point pain
      scale. Secondary outcomes were symptoms measured by the Levine symptom severity
      scale, function measured by Pransky's upper extremity function scale, and grip
      strength. RESULTS: Pain decreased during the two week placebo run-in period in
      both the sham device and placebo pill groups, but changes were not different
      between the groups (-0.14, 95% confidence interval -0.52 to 0.25, P = 0.49).
      Changes in severity scores for arm symptoms and grip strength were similar
      between groups, but arm function improved more in the placebo pill group (2.0,
      0.06 to 3.92, P = 0.04). Longitudinal regression analyses that followed
      participants throughout the treatment period showed significantly greater
      downward slopes per week on the 10 point arm pain scale in the sham device group
      than in the placebo pill group (-0.33 (-0.40 to -0.26) v -0.15 (-0.21 to -0.09),
      P = 0.0001) and on the symptom severity scale (-0.07 (-0.09 to -0.05) v -0.05 (
      0.06 to -0.03), P = 0.02). Differences were not significant, however, on the
      function scale or for grip strength. Reported adverse effects were different in
      the two groups. CONCLUSIONS: The sham device had greater effects than the placebo
      pill on self reported pain and severity of symptoms over the entire course of
      treatment but not during the two week placebo run in. Placebo effects seem to be
      malleable and depend on the behaviours embedded in medical rituals.

PMID- 16452104
TI  - Does IQ explain socioeconomic inequalities in health? Evidence from a population
      based cohort study in the west of Scotland.
AB  - OBJECTIVE: To test the hypothesis that IQ is a fundamental cause of socioeconomic
      inequalities in health. DESIGN: Cross sectional and prospective cohort study, in
      which indicators of IQ were assessed by written test and socioeconomic position
      by self report. SETTING: West of Scotland. PARTICIPANTS: 1347 people (739 women)
      aged 56 in 1987. MAIN OUTCOME MEASURES: Total mortality and coronary heart
      disease mortality (ascertained between 1987 and 2004); respiratory function, self
      reported minor psychiatric morbidity, long term illness, and self perceived
      health (all assessed in 1988). RESULTS: In sex adjusted analyses, indices of
      socioeconomic position (childhood and current social class, education, income,
      and area deprivation) were significantly associated with each health outcome.
      Thus the greatest risk of ill health and mortality was evident in the most
      socioeconomically disadvantaged groups, as expected. After adjustment for IQ, a
      marked attenuation in risk occurred for poor mental health (range of attenuation
      in risk ratio across the five socioeconomic indicators: 15-58%), long term
      illness (25-53%), poor self perceived health (41-56%), respiratory function (44
      66%), coronary heart disease mortality (31-111%), and total mortality (45-131%).
      Despite the clear reduction in the magnitude of these effects after controlling
      for IQ, in half of the associations examined the risk of ill health in
      socioeconomically disadvantaged people was still at least twice that of
      advantaged people. Statistical significance was lost for only 5/25 separate
      socioeconomic health gradients that showed significant relations in sex adjusted
      analyses. CONCLUSIONS: Scores from the IQ test used here did not completely
      explain the socioeconomic gradients in health. However, controlling for IQ did
      lead to a marked reduction in the magnitude of these gradients. Further
      exploration of the currently scant information about IQ, socioeconomic position,
      and health is needed.

PMID- 16452106
TI  - Disentangling contextual effects on cause-specific mortality in a longitudinal 23
      year follow-up study: impact of population density or socioeconomic environment?
AB  - BACKGROUND: Various studies have investigated urban/rural differences in cause
      specific mortality. A separate body of literature has analysed effects of
      socioeconomic environment on mortality. Almost no studies have attempted to
      disentangle effects of population density and socioeconomic environment on
      mortality, beyond the effects of individual characteristics. METHODS: Considering
      all individuals living in the region of Scania, Sweden, from 1970-93, we
      performed 10 year mortality follow-ups on (i) individuals aged 55, (ii)
      individuals aged 65, and (iii) individuals aged 75 years at baseline. Cox
      multilevel models adjusted for individual factors allowed us to investigate the
      independent effects of population density and median income in the parish of
      residence on mortality from ischaemic heart disease (IHD), lung cancer, and
      chronic obstructive pulmonary disease (COPD) among individuals who had lived in
      the same parish for at least 10 years prior to mortality follow-up. RESULTS: In
      females, as in males, after adjustment for individual and contextual
      socioeconomic status, we found a dose-response association between population
      density and mortality from lung cancer and COPD in all age groups investigated,
      and from IHD especially in the youngest age group. Overall, the population
      density effect was the strongest on lung cancer mortality. Median income had an
      additional impact only in 2 out of 16 subgroups of age x gender x cause of death.
      CONCLUSIONS: In our region-wide study conducted at the parish level, contextual
      disparities in mortality were dominated by the population density effect.
      However, it may be unwise to conclude that truly contextual effects exist on
      mortality, before identification of plausible mediating processes through which
      urbanicity may influence mortality risk.

PMID- 16452105
TI  - Fetal lung volume in congenital diaphragmatic hernia.
AB  - In a retrospective study of 22 neonates with congenital diaphragmatic hernia,
      fetal lung volume (FLV) measured by magnetic resonance imaging was associated
      with survival; the best FLV ratio cut-off to predict mortality was 30% of
      expected FLV. This study supports a correlation between FLV and the chances of
      survival.

PMID- 16452107
TI  - Cohort profile: the Aberdeen children of the 1950s study.

PMID- 16452108
TI  - Oxidative stress induces internalization of the bile salt export pump, Bsep, and
      bile salt secretory failure in isolated rat hepatocyte couplets: a role for
      protein kinase C and prevention by protein kinase A.
AB  - We have shown that Ca2+-mediated protein kinase C (PKC) activation induces
      impairment of bile salt secretory function and F-actin redistribution in
      hepatocyte couplets. Because oxidative stress induces Ca2+ elevation, we tested
      here whether PKC inhibition or protein kinase A (PKA) activation, which often
      counteracts PKC-dependent effects, can prevent and reverse these alterations. The
      pro-oxidant compounds tert-butylhydroperoxide (tBOOH, 100 microM) and 2,3
      dimethoxy-1,4-naphthoquinone (30 microM), reduced by -41% and -29%, respectively,
      the percentage of couplets accumulating the fluorescent bile salt analog, cholyl
      lysylfluorescein in their canalicular vacuoles (p < 0.01). tBOOH-induced bile
      salt secretory failure was accompanied by internalization of the canalicular bile
      salt export pump (Bsep), and disarrangement of cytoskeletal F-actin. All these
      deleterious effects were fully prevented by the intracellular Ca2+ chelator
      BAPTA/AM (20 microM), the pan-specific PKC inhibitors H7 (100 microM) and
      staurosporine (1 microM), the inhibitor of Ca2+-dependent PKCs, Go6976 (2
      microM), and the PKA activator dibutyryl-cAMP (500 microM). H7, Go6976, and
      dibutyryl-cAMP not only prevented but also fully reversed the decrease in the
      cholyl-lysyl-fluorescein accumulation. In conclusion, these results suggest that
      low levels of oxidative stress impair bile salt secretion by internalizing Bsep
      through a Ca2+-dependent, PKC-mediated mechanism, and that inhibition of PKC, or
      activation of PKA, prevents and reverses these effects. Alterations in actin
      organization may be a causal factor.

PMID- 16452110
TI  - Cortical bone geometry in asthmatic children.
AB  - At the mid-radius, pre-pubertal asthmatic children had smaller periosteal and
      endosteal circumferences and thicker cortical shells compared to controls, when
      assessed by peripheral quantitative computed tomography. Asthmatics had
      diminished periosteal expansion for muscle size, suggesting that asthma, its
      treatment, or its effects on physical activity had resulted in impaired
      adaptation of bone to muscle loading. Alterations in cortical bone geometry might
      explain the increased fracture risk in asthmatic children.

PMID- 16452109
TI  - Mothers' postpartum psychological adjustment and infantile colic.
AB  - BACKGROUND: Infantile colic is a common problem of early infancy. There is
      limited data on the relation between postpartum maternal psychological problems
      and colic. AIM: : To investigate whether infantile colic is associated with
      postpartum mood disorders or insecure adult attachment style of the mother.
      METHODS: Seventy eight mothers and newborns were enrolled in this prospective,
      longitudinal study. Maternal depressive symptoms were screened with Edinburgh
      Postpartum Depression Score (EPDS) and maternal anxiety was assessed with State
      Trait Anxiety Inventory (STAI). The Adult Attachment Scale was used to determine
      the attachment style of the mother. Infantile colic was defined according to
      Wessel criteria. RESULTS: Infantile colic was present in 17 infants (21.7%);
      12.9% of the mothers had an EPDS > or =13. The mean EPDS of the mothers whose
      infants had infantile colic (10.2+/-6.0) was significantly higher than that of
      the mothers of infants without colic (6.3+/-4.0). Among infants with infantile
      colic, 62.5% had mothers who had insecure attachment style, whereas only 31.1% of
      mothers had insecure attachment when the infant did not have infantile colic.
      CONCLUSION: Postpartum maternal depressive symptoms and insecure attachment style
      are associated with infantile colic. Screening and early intervention of
      postpartum depression might promote the health of both the mother and infant.

PMID- 16452111
TI  - MAMMOT--a set of tools for the design, management and visualization of genomic
      tiling arrays.
AB  - The MAMMOT software suite is a collection of Perl and PHP scripts for designing,
      annotating and visualizing genome tiling arrays to, for example, facilitate
      studies into the epigenetics of gene regulation. The web design allows rapid
      experimental data entry from multiple users, and results can easily be shared
      between groups and individuals. AVAILABILITY: http://www.mammot.org.uk/ CONTACT:
      e.ryder@gen.cam.ac.uk.

PMID- 16452112
TI  - Efficient estimation of graphlet frequency distributions in protein-protein
      interaction networks.
AB  - MOTIVATION: Algorithmic and modeling advances in the area of protein-protein
      interaction (PPI) network analysis could contribute to the understanding of
      biological processes. Local structure of networks can be measured by the
      frequency distribution of graphlets, small connected non-isomorphic induced
      subgraphs. This measure of local structure has been used to show that high
      confidence PPI networks have local structure of geometric random graphs. Finding
      graphlets exhaustively in a large network is computationally intensive. More
      complete PPI networks, as well as PPI networks of higher organisms, will thus
      require efficient heuristic approaches. RESULTS: We propose two efficient and
      scalable heuristics for finding graphlets in high-confidence PPI networks. We
      show that both PPI and their model geometric random networks, have defined
      boundaries that are sparser than the 'inner parts' of the networks. In addition,
      these networks exhibit 'uniformity' of local structure inside the networks. Our
      first heuristic exploits these two structural properties of PPI and geometric
      random networks to find good estimates of graphlet frequency distributions in
      these networks up to 690 times faster than the exhaustive searches. Our second
      heuristic is a variant of a more standard sampling technique and it produces
      accurate approximate results up to 377 times faster than the exhaustive searches.
      We indicate how the combination of these approaches may result in an even better
      heuristic. AVAILABILITY: Supplementary information is available at
      http://www.cs.toronto.edu/~natasha/BIOINF-2005-0946/Supplementary.pdf. Software
      implementing the algorithms is available at
      http://www.cs.toronto.edu/~natasha/BIOINF-2005-0946/estimate_grap-hlets.html.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 16452113
TI  - Structured polychotomous machine diagnosis of multiple cancer types using gene
      expression.
AB  - MOTIVATION: The problem of class prediction has received a tremendous amount of
      attention in the literature recently. In the context of DNA microarrays, where
      the task is to classify and predict the diagnostic category of a sample on the
      basis of its gene expression profile, a problem of particular importance is the
      diagnosis of cancer type based on microarray data. One method of classification
      which has been very successful in cancer diagnosis is the support vector machine
      (SVM). The latter has been shown (through simulations) to be superior in
      comparison with other methods, such as classical discriminant analysis, however,
      SVM suffers from the drawback that the solution is implicit and therefore is
      difficult to interpret. In order to remedy this difficulty, an analysis of
      variance decomposition using structured kernels is proposed and is referred to as
      the structured polychotomous machine. This technique utilizes Newton-Raphson to
      find estimates of coefficients followed by the Rao and Wald tests, respectively,
      for addition and deletion of import vectors. RESULTS: The proposed method is
      applied to microarray data and simulation data. The major breakthrough of our
      method is efficiency in that only a minimal number of genes that accurately
      predict the classes are selected. It has been verified that the selected genes
      serve as legitimate markers for cancer classification from a biological point of
      view. AVAILABILITY: All source codes used are available on request from the
      authors.

PMID- 16452114
TI  - Memory efficient folding algorithms for circular RNA secondary structures.
AB  - BACKGROUND: A small class of RNA molecules, in particular the tiny genomes of
      viroids, are circular. Yet most structure prediction algorithms handle only
      linear RNAs. The most straightforward approach is to compute circular structures
      from 'internal' and 'external' substructures separated by a base pair. This is
      incompatible, however, with the memory-saving approach of the Vienna RNA Package
      which builds a linear RNA structure from shorter (internal) structures only.
      RESULT: Here we describe how circular secondary structures can be obtained
      without additional memory requirements as a kind of 'post-processing' of the
      linear structures. AVAILABILITY: The circular folding algorithm is implemented in
      the current version of the of RNAfold program of the Vienna RNA Package, which
      can be downloaded from http://www.tbi.univie.ac.at/RNA/

PMID- 16452115
TI  - Dynamics of subcutaneous tissue response to the implantation of tetracycline
      treated or untreated membrane of demineralized bovine cortical bone in rats.
AB  - This study aims to conduct a histological evaluation of tissue response to a
      membrane obtained from demineralized bovine cortical bone, associated or not, to
      tetracycline (TTC). TTC treated and untreated bovine membranes were implanted in
      the subcutaneous tissue of rats (n = 120). The animals were killed 1, 3, 7, 15,
      30, and 60 days after surgery. The tissue around the material was fixed in 10%
      buffered formalin for 24 h. Sections of 6 mm were stained with hematoxylin and
      eosin. In general, moderate to intense inflammatory response was observed in the
      initial periods (1 and 3 days), moderate response in the 7- and 15-day periods,
      and that was remarkably reduced at 30 and 60 days. Resorptions of the membranes
      by mononuclear cells (fibroblasts and macrophages) and multinucleated giant cells
      were observed 15 days after implantation. Only the remnants of the material could
      be detected in some animals in 60 days. Both membranes were tolerated by the
      tissue and were completely resorbed after 30-60 days. While the association of
      TTC apparently accelerated the biodegradability of the membrane substrate, no
      significant differences were found in the tissue response behavior between the
      two groups tested.

PMID- 16452116
TI  - The evolutionary origin of peroxisomes: an ER-peroxisome connection.
AB  - The peroxisome is an essential eukaryotic organelle, crucial for lipid metabolism
      and free radical detoxification, development, differentiation, and morphogenesis
      from yeasts to humans. Loss of peroxisomes invariably leads to fatal peroxisome
      biogenesis disorders in man. The evolutionary origin of peroxisomes remains
      unsolved; proposals for either a symbiogenetic or cellular membrane invagination
      event are unconclusive. To address this question, we have probed with a
      peroxisomal proteome, an "ensemble" of 19 representative eukaryotic complete
      genomes. Molecular phylogenetic and sequence comparison tools allowed us to
      identify four proteins as peroxisomal markers for unequivocal in silico
      peroxisome detection. We have then detected the Apicomplexa phylum as the first
      group of organisms devoid of peroxisomes, in the presence of mitochondria.
      Finally, we deliver evidence against a prokaryotic ancestor of peroxisomes: (1)
      the peroxisomal membrane is composed of purely eukaryotic bricks and is thus
      useful to trace the eukaryotes in their evolutionary paths and (2) the
      peroxisomal matrix protein import system shares mechanistic similarities with the
      endoplasmic reticulum/proteasome degradation process, indicating a common
      evolutionary history.

PMID- 16452118
TI  - The relationship between chain connectivity and domain stability in the
      equilibrium and kinetic folding mechanisms of dihydrofolate reductase from
      E.coli.
AB  - The role of domains in defining the equilibrium and kinetic folding properties of
      dihydrofolate reductase (DHFR) from Escherichia coli was probed by examining the
      thermodynamic and kinetic properties of a set of variants in which the chain
      connectivity in the discontinuous loop domain (DLD) and the adenosine-binding
      domain (ABD) was altered by permutation. To test the concept that chain cleavage
      can selectively destabilize the domain in which the N- and C-termini are
      resident, permutations were introduced at one position within the ABD, one within
      the DLD and one at a boundary between the domains. The results demonstrated that
      a continuous ABD is required for a stable thermal intermediate and a continuous
      DLD is required for a stable urea intermediate. The permutation at the domain
      interface had both a thermal and urea intermediate. Strikingly, the observable
      kinetic folding responses of all three permuted proteins were very similar to the
      wild-type protein. These results demonstrate a crucial role for stable domains in
      defining the energy surface for the equilibrium folding reaction of DHFR. If
      domain connectivity affects the kinetic mechanism, the effects must occur in the
      sub-millisecond time range.

PMID- 16452117
TI  - Recombination estimation under complex evolutionary models with the coalescent
      composite-likelihood method.
AB  - The composite-likelihood estimator (CLE) of the population recombination rate
      considers only sites with exactly two alleles under a finite-sites mutation model
      (McVean, G. A. T., P. Awadalla, and P. Fearnhead. 2002. A coalescent-based method
      for detecting and estimating recombination from gene sequences. Genetics 160:1231
      1241). While in such a model the identity of alleles is not considered, the CLE
      has been shown to be robust to minor misspecification of the underlying
      mutational model. However, there are many situations where the putative mutation
      and demographic history can be quite complex. One good example is rapidly
      evolving pathogens, like HIV-1. First we evaluated the performance of the CLE and
      the likelihood permutation test (LPT) under more complex, realistic models,
      including a general time reversible (GTR) substitution model, rate heterogeneity
      among sites (Gamma), positive selection, population growth, population structure,
      and noncontemporaneous sampling. Second, we relaxed some of the assumptions of
      the CLE allowing for a four-allele, GTR + Gamma model in an attempt to use the
      data more efficiently. Through simulations and the analysis of real data, we
      concluded that the CLE is robust to severe misspecifications of the substitution
      model, but underestimates the recombination rate in the presence of exponential
      growth, population mixture, selection, or noncontemporaneous sampling. In such
      cases, the use of more complex models slightly increases performance in some
      occasions, especially in the case of the LPT. Thus, our results provide for a
      more robust application of the estimation of recombination rates.

PMID- 16452119
TI  - Increased thermal and organic solvent tolerance of modified horseradish
      peroxidase.
AB  - Horseradish peroxidase (HRP) was modified by maleic anhydride and citraconic
      anhydride. The thermal and organic solvent tolerances of native and modified
      enzyme were compared. These chemical modifications of HRP increased their
      thermostability both in aqueous buffer and some organic solvents, and also
      enhanced their tolerances of some organic solvents. We have studied the unfolding
      of native and modified HRP by heat to determine the conformational stability. The
      temperature at the midpoint of thermal denaturation (T(m)) was increased upon
      modification. Both enthalpy change (DeltaH(m)) and entropy change (DeltaS(m)) for
      unfolding of modified enzyme at T(m) were decreased compared with native enzyme.
      Circular dichroism studies proved that these modifications changed the
      conformation of HRP. The improvements of stability are related to side chain
      reorientations of aromatics upon both modifications.

PMID- 16452120
TI  - Studies on transcriptional regulation of endogenous genes by ERF2 transcription
      factor in tobacco cells.
AB  - In this study, we showed that overexpression of ethylene-responsive transcription
      factor (ERF) 2 activated the expression of endogenous genes that have the GCC box
      in their promoter region, in tobacco plants. These include not only a defense
      related gene, CHN50, encoding class I basic chitinase, but also a transcriptional
      repressor gene, ERF3. In tobacco plants constitutively expressing
      ERF2:glucocorticoid receptor fusion protein, treatment with dexamethazone induced
      a rapid increase of ERF3 mRNA and a slow increase of CHN50 mRNA. These results
      suggest that an antagonistic interplay of ERF2 and ERF3 is involved in the
      transcriptional regulation of the class I basic chitinase genes in tobacco.

PMID- 16452121
TI  - Whole heart action potential duration restitution properties in cardiac patients:
      a combined clinical and modelling study.
AB  - Steep action potential duration (APD) restitution has been shown to facilitate
      wavebreak and ventricular fibrillation. The global APD restitution properties in
      cardiac patients are unknown. We report a combined clinical electrophysiology and
      computer modelling study to: (1) determine global APD restitution properties in
      cardiac patients; and (2) examine the interaction of the observed APD restitution
      with known arrhythmia mechanisms. In 14 patients aged 52-85 years undergoing
      routine cardiac surgery, 256 electrode epicardial mapping was performed.
      Activation-recovery intervals (ARI; a surrogate for APD) were recorded over the
      entire ventricular surface. Mono-exponential restitution curves were constructed
      for each electrode site using a standard S1-S2 pacing protocol. The median
      maximum restitution slope was 0.91, with 27% of all electrode sites with
      slopes<0.5, 29% between 0.5 and 1.0, and 20% between 1.0 and 1.5. Eleven per cent
      of restitution curves maintained slope>1 over a range of diastolic intervals of
      at least 30 ms; and 0.3% for at least 50 ms. Activation-recovery interval
      restitution was spatially heterogeneous, showing regional organization with
      multiple discrete areas of steep and shallow slope. We used a simplified computer
      model of 2-D cardiac tissue to investigate how heterogeneous APD restitution can
      influence vulnerability to, and stability of re-entry. Our model showed that
      heterogeneity of restitution can act as a potent arrhythmogenic substrate, as
      well as influencing the stability of re-entrant arrhythmias. Global epicardial
      mapping in humans showed that APD restitution slopes were organized into regions
      of shallow and steep slopes. This heterogeneous organization of restitution may
      provide a substrate for arrhythmia.

PMID- 16452122
TI  - Chemoreflex sympathoexcitation was not altered by the antagonism of glutamate
      receptors in the commissural nucleus tractus solitarii in the working heart
      brainstem preparation of rats.
AB  - The changes in thoracic sympathetic nerve activity, heart rate and frequency of
      phrenic nerve discharge in response to chemoreflex activation before and after
      bilateral microinjections of glutamate receptor antagonists into the comissural
      nucleus tractus solitarii (cNTS) were evaluated in the working heart-brainstem
      preparation of rats. Microinjections of kynurenic acid (KYN, 250 mM), (+/-)-alpha
      methyl-4-carboxyphenylglycine (MCPG, 100 mM), or KYN plus MCPG into the cNTS were
      performed in three different groups. These microinjections into the cNTS did not
      affect the increase in the thoracic sympathetic nerve activity elicited by
      chemoreflex activation (KYN, 54 +/- 3 versus 51 +/- 2%, n = 11; MCPG, 48 +/- 5
      versus 54 +/- 5%, n = 7; and KYN plus MCPG, 57 +/- 6 versus 55 +/- 3%, n = 5).
      The increase in the frequency of the phrenic nerve discharge in response to
      chemoreflex activation was also not affected by KYN (0.28 +/- 0.02 versus 0.30 +/
      0.04 Hz), MCPG (0.27 +/- 0.03 versus 0.27 +/- 0.04 Hz), or KYN plus MCPG (0.30
      +/- 0.04 versus 0.20 +/- 0.03 Hz). The bradycardic response to chemoreflex
      activation was significantly reduced after microinjection of KYN at 2 (-220 +/-
      16 versus -50 +/- 6 beats min(-1)) and 10 min (-220 +/- 16 versus -65 +/- 9 beats
      min(-1)) and after microinjection of KYN plus MCPG into the NTS it was abolished
      at 2 (-192 +/- 14 versus -2 +/- 1 beats min(-1)) and 10 min (-192 +/- 14 versus 
      4 +/- 2 beats min(-1)). These data support the hypothesis that the
      neurotransmission of the sympathoexcitatory and respiratory components of the
      chemoreflex in the cNTS involves neurotransmitters other than L-glutamate and
      also the concept that the parasympathetic component of this reflex is mediated by
      L-glutamate.

PMID- 16452123
TI  - Correlation of alpha-skeletal actin expression, ventricular fibrosis and heart
      function with the degree of pressure overload cardiac hypertrophy in rats.
AB  - We have analysed alterations of alpha-skeletal actin expression and volume
      fraction of fibrosis in the ventricular myocardium and their functional
      counterpart in terms of arrhythmogenesis and haemodynamic variables, in rats with
      different degrees of compensated cardiac hypertrophy induced by infra-renal
      abdominal aortic coarctation. The following coarctation calibres were used: 1.3
      (AC1.3 group), 0.7 (AC0.7) and 0.4 mm (AC0.4); age-matched rats were used as
      controls (C group). One month after surgery, spontaneous and sympathetic-induced
      ventricular arrhythmias were telemetrically recorded from conscious freely moving
      animals, and invasive haemodynamic measurements were performed in anaesthetized
      animals. After killing, subgroups of AC and C rats were used to evaluate in the
      left ventricle the expression and spatial distribution of alpha-skeletal actin
      and the amount of perivascular and interstitial fibrosis. As compared with C, all
      AC groups exhibited higher values of systolic pressure, ventricular weight and
      ventricular wall thickness. AC0.7 and AC0.4 rats also showed a larger amount of
      fibrosis and upregulation of alpha-skeletal actin expression associated with a
      higher vulnerability to ventricular arrhythmias (AC0.7 and AC0.4) and enhanced
      myocardial contractility (AC0.4). Our results illustrate the progressive changes
      in the extracellular matrix features accompanying early ventricular remodelling
      in response to different degrees of pressure overload that may be involved in the
      development of cardiac electrical instability. We also demonstrate for the first
      time a linear correlation between an increase in alpha-skeletal actin expression
      and the degree of compensated cardiac hypertrophy, possibly acting as an early
      compensatory mechanism to maintain normal mechanical performance.

PMID- 16452124
TI  - Effects of diet and osmotic pressure on Na+ transport and tissue conductance of
      sheep isolated rumen epithelium.
AB  - The intention of this study was to determine the effects of mucosal osmotic
      pressure on transport and barrier functions of the rumen epithelium of sheep,
      which were fed various diets: hay ad libitum, or 600, 1200 or 1800 g day(-1) of a
      supplemented diet plus hay ad libitum. The experiments were conducted by using
      the conventional Ussing chamber technique. Mucosal osmolarity was adjusted to 300
      (control), 375 or 450 mosmol l(-1). Feeding of a supplemented diet led to a
      significant increase of mucosal to serosal Na+ transport and net Na+ transport,
      probably because of an increase of apical Na+-H+ exchange activity. An increase
      in mucosal osmotic pressure: (a) reduced net Na+ transport in all feeding groups,
      the remaining net Na+ transport being higher in tissues of sheep fed a
      supplemented diet; (b) increased transepithelial tissue conductance, this rise
      being smallest with a high intake of the supplemented diet; and (c) enhanced the
      serosal to mucosal Na+ transport in tissues of hay-fed sheep and sheep fed with
      600 g day(-1) of the supplemented diet, while higher intakes of the supplemented
      diet (1200 and 1800 g) did not produce any effect. All these changes indicate a
      diet-dependent adaptation to luminal hypertonicity.

PMID- 16452125
TI  - Aggregate formation and phosphorylation of neurofilament-L Pro22 Charcot-Marie
      Tooth disease mutants.
AB  - Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral nerve
      disorder. The causative gene for axonal type CMT2E has been identified as
      neurofilament light (NF-L) chain. Using cultured cells and in vitro assays, we
      analyzed the filament formation ability of Pro22 CMT mutant proteins of NF-L,
      P22S and P22T. NF-L Pro22 mutant proteins formed large aggregates in SW13- cells
      and cortical neurons and assembled into short twisty threads thinner than 10 nm
      filaments in vitro. Those threads associated with each other at their ends and
      entangled into large aggregates, also abnormalities, were detected at steps in
      oligomer formation. Pro22 mutations abolished Thr21 phosphorylation by cyclin
      dependent kinase 5 and external signal regulated kinase, which suppressed
      filament assembly, but phosphorylation by protein kinase A (PKA) inhibited
      aggregate formation in vitro and alleviated aggregates in cortical neurons. These
      results indicate that the Pro22 CMT mutation induces abnormal filament aggregates
      by disrupting proper oligomer formation and the aggregates are mitigated by
      phosphorylation with PKA, which makes it a viable target for the development for
      therapeutics.

PMID- 16452127
TI  - Creating political will: moving from the science to the art of health promotion.

PMID- 16452128
TI  - Lessons learned from recruiting young female students to a randomised controlled
      trial of chlamydia screening.
AB  - BACKGROUND: Recruitment is a problem in many trials. Two female medical students
      offered to help with recruiting problems in a community-based trial of chlamydia
      screening to prevent pelvic inflammatory disease. We need to recruit 2500
      sexually active female students and ask them to provide a self-taken low vaginal
      swab and complete a questionnaire with follow-up after a year. OBJECTIVES: To
      identify recruitment difficulties in a community-based trial of chlamydia
      screening and to investigate how they might be overcome. DESIGN: Descriptive
      study. SETTING: London South Bank and Kingston Universities. METHODS: The
      students observed the recruitment methods used for the first 4 months of the
      trial. This comprised single researchers recruiting individual women in student
      bars and common rooms. With the researchers they piloted a new method of group
      recruitment with pairs of researchers making announcements at the end of lectures
      after first sending out all male students and those aged>25 years. This involved
      extra time planning and liaising with the lecturers in advance of recruitment
      sessions. RESULTS: The recruitment rate had been averaging only 25 participants
      per week. Many students were ineligible: never been sexually active, too old,
      recently been tested for chlamydia. Many eligible students were reluctant to take
      part because of embarrassment or anxiety about providing a swab. Using a new
      method of group recruitment after lectures we recruited 192 participants in 2
      weeks. CONCLUSION: For a study on a sensitive topic, two researchers recruiting
      women in groups after lectures may be a more effective and cost-effective way
      than individual recruitment by researchers working alone.

PMID- 16452126
TI  - MYC-containing double minutes in hematologic malignancies: evidence in favor of
      the episome model and exclusion of MYC as the target gene.
AB  - Double minutes (dmin)-circular, extra-chromosomal amplifications of specific
      acentric DNA fragments-are relatively frequent in malignant disorders,
      particularly in solid tumors. In acute myeloid leukemia (AML) and myelodysplastic
      syndromes (MDS), dmin are observed in approximately 1% of the cases. Most of them
      consist of an amplified segment from chromosome band 8q24, always including the
      MYC gene. Besides this information, little is known about their internal
      structure. We have characterized in detail the genomic organization of 32 AML and
      two MDS cases with MYC-containing dmin. The minimally amplified region was shown
      to be 4.26 Mb in size, harboring five known genes, with the proximal and the
      distal amplicon breakpoints clustering in two regions of approximately 500 and
      600 kb, respectively. Interestingly, in 23 (68%) of the studied cases, the
      amplified region was deleted in one of the chromosome 8 homologs at 8q24,
      suggesting excision of a DNA segment from the original chromosomal location
      according to the 'episome model'. In one case, sequencing of both the dmin and
      del(8q) junctions was achieved and provided definitive evidence in favor of the
      episome model for the formation of dmin. Expression status of the TRIB1 and MYC
      genes, encompassed by the minimally amplified region, was assessed by northern
      blot analysis. The TRIB1 gene was found over-expressed in only a subset of the
      AML/MDS cases, whereas MYC, contrary to expectations, was always silent. The
      present study, therefore, strongly suggests that MYC is not the target gene of
      the 8q24 amplifications.

PMID- 16452129
TI  - Chromosomal numerical abnormality profiles of gastrointestinal stromal tumors.
AB  - BACKGROUND: Biological variations in and the heterogeneity of gastrointestinal
      stromal tumors (GISTs) are well known, but chromosomal numerical abnormality
      (CNA) has not been fully examined especially in this context. The aim of this
      study is to test CNA as a possible biological predictor of biological behavior of
      GISTs. METHOD: We applied microwave-assisted FISH protocol to pathological
      archives of GIST tumors displaying different clinical features to characterize
      the CNA profile of these tumors. A panel of 18 centromere enumeration probes
      (CEP) and 24 bacterial artificial chromosome (BAC) or P1-derived artificial
      chromosome (PAC) probes containing genes like Aurora kinases (AURKs) and other
      candidate genes involved in human carcinogenesis were used. CNA profiles,
      histopathological risk categorization and Ki-67 labeling indexes of 23 primary
      and/or metastatic GIST tumors of 12 subjects (both primary and metastatic in 7
      subjects) were compared between primary GIST with and without metastases, and
      between metastatic and primary portions in 7 individuals. RESULTS: CNA in the
      primary sites was more extensive in the GISTs with recurrence and metastasis than
      in those without, especially as to the loss of chromosome 20 and genomic
      imbalance of AURKA-containing BAC probe on 20q in the cases with metastasis. The
      consistent loss of one allele of chromosome 14q was also noted. Interestingly,
      both primary and metastatic tumors in identical individuals had similar CNA
      profiles. CONCLUSION: The extent of CNA differed between GISTS with and without
      recurrence or metastasis; thus, FISH analysis of specimens from the primary sites
      may predict the biological behavior of this tumor.

PMID- 16452131
TI  - Determinants of accident proneness: a case-control study in railway workers.
AB  - BACKGROUND: Accident proneness or workers who have more frequent occupational
      injuries is common but the role of occupational and individual factors has rarely
      been studied. AIM: To assess the relationships of certain occupational and
      individual characteristics with frequency of occupational injuries. METHOD: This
      case-control study included 1305 male workers with occupational injuries during
      1999-2000 and 1305 controls from a railway company. A standardized questionnaire
      was completed by the occupational physician in the presence of the subject. The
      data were analysed using logistic regression. RESULTS: Having more than one
      injury was associated with short service in the present job, younger age, sleep
      disorders, smoking, requesting a job change, physical disability and lack of
      physical activity. Safety training was negatively related to injury frequency.
      Short service in the present job was the only significant factor for single
      injuries. CONCLUSION: This study identified a number of work and individual
      factors that predicted occupational injury frequency and may be useful in
      designing preventative measures. Occupational physicians could assist workers to
      be more aware of the risks and to find remedial measures.

PMID- 16452130
TI  - A case-control study of risk factors for arm pain presenting to primary care
      services.
AB  - OBJECTIVES: To investigate the association of occupational activities, mental
      health and comorbidity with care seeking for arm pain, and to test the hypothesis
      that specific disorders arise from physical risk factors and non-specific pain
      from psychological ones. METHODS: Patients with a new episode of arm pain and
      matched controls were recruited from eight general practices. A questionnaire
      about risk factors was completed and cases were classified using a validated
      examination schedule. Questions were asked about occupational activities and
      psychosocial stressors. Mental health was assessed using the Hospital Anxiety
      Depression Scale, elements of the Brief Symptom Inventory (somatizing tendency)
      and the Whiteley Index (health anxiety); comorbidity from chronic fatigue
      syndrome (CFS) and chronic widespread pain (CWP) was ascertained using standard
      definitions. Associations were explored using logistic regression and summarized
      as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS:
      Altogether, 132 cases and 127 controls were studied. Consulting with arm pain was
      strongly associated with all of the mental health variables and with CFS and CWP,
      irrespective of the site of arm pain or diagnosis. The OR in those with >3 versus
      <3 distressing somatic symptoms was 3.9 (95% CI 1.7-9.0). There were several
      significant associations with physical activity, but none with occupational
      psychosocial stressors. Repeated wrist/finger movements and carrying weights were
      more strongly associated with specific diagnoses than with non-specific pain.
      CONCLUSIONS: Somatizing tendency, health anxiety, low mood, CFS and CWP are more
      common in arm pain consulters. Certain mechanical activities are also
      overrepresented, particularly in those with specific pathology.

PMID- 16452132
TI  - Disability management through positive intervention in stakeholders' information
      asymmetry. A pilot study.
AB  - BACKGROUND: One increasingly attractive hypothesis to account for prolonged
      sickness absence from work is the presence of 'information asymmetry' among
      stakeholders. Information asymmetry refers to a situation in which critical
      information is not (appropriately) exchanged, in this case among those involved
      in disability management. AIM: The purpose of this study was to intervene
      positively in the information asymmetry that currently exists between social
      insurance physicians and occupational physicians in Belgium. METHODS: We
      developed a novel model aimed at improving information exchange, and a pilot
      study protocol based on the model. Our first objective was to investigate
      feasibility of implementing the study protocol. Our second and main objective was
      to obtain preliminary results on whether improving information exchange between
      physicians would facilitate work resumption of employees out on sickness absence.
      RESULTS: Of 126 patients recruited, 91 were eligible and assigned to one of two
      groups: a control group, whose physicians used the standard Belgian evaluation
      protocol, and an intervention group, whose physicians used our new protocol.
      Outcome parameters from the 15 patients assigned to the intervention group
      revealed that enhanced inter-physician information exchange produced favourable
      work resumption rates (73%), suggesting that both the model and study protocol
      show promise. CONCLUSIONS: The issue of sharing information among all
      stakeholders involved in disability management is an important one. Moreover,
      professional reintegration of employees after a sickness absence is universally
      important to occupational health practitioners. Our preliminary results suggest
      that reducing information asymmetry among physicians should be investigated
      further in larger intervention trials.

PMID- 16452133
TI  - Aberrant nucleo-cytoplasmic cross-talk results in donor cell mtDNA persistence in
      cloned embryos.
AB  - Mitochondrial DNA is an extranuclear genome normally maternally inherited through
      the oocyte. However, the use of nuclear transfer can result in both donor cell
      and recipient oocyte mitochondrial DNA persisting through to blastocyst and being
      transmitted to the offspring. The degree of donor mitochondrial DNA transmission
      appears to be random and currently no evidence exists to explain this phenomenon.
      To determine whether this is a dilution factor or directly related to the
      transcriptional status of the donor cell in respect of mitochondrial DNA
      transcription factors, we have generated sheep nuclear transfer embryos using
      donor cells: (1) possessing their full mitochondrial DNA complement, (2) those
      partially depleted, and (3) those depleted but containing residual levels. For
      each donor type, donor mitochondrial DNA persisted in some blastocysts. It is
      evident from the donor cells used that nuclear-encoded mitochondrial DNA
      transcription and replication factors persist even after mitochondrial DNA
      depletion, as do transcripts for some of the mitochondrial-encoded genes. These
      cells are therefore still programmed to drive mitochondrial DNA replication and
      transcription. In nuclear transfer-derived embryos, we have observed the
      persistence of these nuclear-encoded mitochondrial DNA transcription and
      replication factors but not in those embryos generated through in vitro
      fertilization. Consequently, nucleo-mitochondrial interaction following nuclear
      transfer is out of sequence as the onset of mitochondrial replication is a
      postimplantation event.

PMID- 16452134
TI  - Genomic organization of gypsy chromatin insulators in Drosophila melanogaster.
AB  - Chromatin insulators have been implicated in the regulation of higher-order
      chromatin structure and may function to compartmentalize the eukaryotic genome
      into independent domains of gene expression. To test this possibility, we used
      biochemical and computational approaches to identify gypsy-like genomic-binding
      sites for the Suppressor of Hairy-wing [Su(Hw)] protein, a component of the gypsy
      insulator. EMSA and FISH analyses suggest that these are genuine Su(Hw)-binding
      sites. In addition, functional tests indicate that genomic Su(Hw)-binding sites
      can inhibit enhancer-promoter interactions and thus function as bona fide
      insulators. The insulator strength is dependent on the genomic location of the
      transgene and the number of Su(Hw)-binding sites, with clusters of two to three
      sites showing a stronger effect than individual sites. These clusters of Su(Hw)
      binding sites are located mostly in intergenic regions or in introns of large
      genes, an arrangement that fits well with their proposed role in the formation of
      chromatin domains. Taken together, these data suggest that genomic gypsy-like
      insulators may provide a means for the compartmentalization of the genome within
      the nucleus.

PMID- 16452135
TI  - Smc5p promotes faithful chromosome transmission and DNA repair in Saccharomyces
      cerevisiae.
AB  - Heterodimers of structural maintenance of chromosomes (SMC) proteins form the
      core of several protein complexes involved in the organization of DNA, including
      condensation and cohesion of the chromosomes at metaphase. The functions of the
      complexes with a heterodimer of Smc5p and Smc6p are less clear. To better
      understand them, we created two S. cerevisiae strains bearing temperature
      sensitive alleles of SMC5. When shifted to the restrictive temperature, both
      mutants lose viability gradually, concomitant with the appearance of nuclear
      abnormalities and phosphorylation of the Rad53p DNA damage checkpoint protein.
      Removal of Rad52p or overexpression of the SUMO ligase Mms21p partially
      suppresses the temperature sensitivity of smc5 strains and increases their
      survival at the restrictive temperature. At the permissive temperature, smc5-31
      but not smc5-33 cells exhibit hypersensitivity to several DNA-damaging agents
      despite induction of the DNA damage checkpoint. Similarly, smc5-31 but not smc5
      33 cells are killed by overexpression of the SUMO ligase-defective Mms21-SAp but
      not by overexpression of wild-type Mms21p. Both smc5 alleles are synthetically
      lethal with mms21-SA and exhibit Rad52p-independent chromosome fragmentation and
      loss at semipermissive temperatures. Our data indicate a critical role for the S.
      cerevisiae Smc5/6-containing complexes in both DNA repair and chromosome
      segregation.

PMID- 16452136
TI  - The C terminus of collagen SQT-3 has complex and essential functions in nematode
      collagen assembly.
AB  - The nematode exoskeleton is a multilayered structure secreted by the underlying
      hypodermal cells and mainly composed of small collagens, which are encoded by a
      large gene family. In previous work, we reported analysis of the C. elegans dpy
      31 locus, encoding a hypodermally expressed zinc-metalloprotease of the BMP
      1/TOLLOID family essential for viability and cuticle deposition. We have
      generated a large set of extragenic suppressors of dpy-31 lethality, most of
      which we show here to be allelic to the cuticle collagen genes sqt-3 and dpy-17.
      We analyzed the interaction among dpy-31, sqt-3, and dpy-17 using a SQT-3
      specific antiserum, which was employed in immunofluorescence experiments. Our
      results support a role for DPY-31 in SQT-3 extracellular processing and suggest
      that the SQT-3 C-terminal nontrimeric region serves multiple roles during SQT-3
      assembly. Different missense mutations of this region have diverse phenotypic
      consequences, including cold-sensitive lethality. Furthermore, the biochemical
      and genetic data indicate that the extracellular assemblies of DPY-17 and SQT-3
      are interdependent, most likely because the collagens are incorporated into the
      same cuticular substructure. We find that absence of DPY-17 causes extensive
      intracellular retention of SQT-3, indicating that formation of the SQT-3-DPY-17
      polymer could begin in the intracellular environment before secretion.

PMID- 16452137
TI  - Mismatch tolerance by DNA polymerase Pol4 in the course of nonhomologous end
      joining in Saccharomyces cerevisiae.
AB  - In yeast, the nonhomologous end joining pathway (NHEJ) mobilizes the DNA
      polymerase Pol4 to repair DNA double-strand breaks when gap filling is required
      prior to ligation. Using telomere-telomere fusions caused by loss of the
      telomeric protein Rap1 and double-strand break repair on transformed DNA as
      assays for NHEJ between fully uncohesive ends, we show that Pol4 is able to
      extend a 3'-end whose last bases are mismatched, i.e., mispaired or unpaired, to
      the template strand.

PMID- 16452138
TI  - Palmitoyl-protein thioesterase 1 deficiency in Drosophila melanogaster causes
      accumulation of abnormal storage material and reduced life span.
AB  - Human neuronal ceroid lipofuscinoses (NCLs) are a group of genetic
      neurodegenerative diseases characterized by progressive death of neurons in the
      central nervous system (CNS) and accumulation of abnormal lysosomal storage
      material. Infantile NCL (INCL), the most severe form of NCL, is caused by
      mutations in the Ppt1 gene, which encodes the lysosomal enzyme palmitoyl-protein
      thioesterase 1 (Ppt1). We generated mutations in the Ppt1 ortholog of Drosophila
      melanogaster to characterize phenotypes caused by Ppt1 deficiency in flies. Ppt1
      deficient flies accumulate abnormal autofluorescent storage material
      predominantly in the adult CNS and have a life span 30% shorter than wild type,
      phenotypes that generally recapitulate disease-associated phenotypes common to
      all forms of NCL. In contrast, some phenotypes of Ppt1-deficient flies differed
      from those observed in human INCL. Storage material in flies appeared as highly
      laminar spherical deposits in cells of the brain and as curvilinear profiles in
      cells of the thoracic ganglion. This contrasts with the granular deposits
      characteristic of human INCL. In addition, the reduced life span of Ppt1
      deficient flies is not caused by progressive death of CNS neurons. No changes in
      brain morphology or increases in apoptotic cell death of CNS neurons were
      detected in Ppt1-deficient flies, even at advanced ages. Thus, Ppt1-deficient
      flies accumulate abnormal storage material and have a shortened life span without
      evidence of concomitant neurodegeneration.

PMID- 16452139
TI  - Efficient gene targeting in Drosophila with zinc-finger nucleases.
AB  - This report describes high-frequency germline gene targeting at two genomic loci
      in Drosophila melanogaster, y and ry. In the best case, nearly all induced
      parents produced mutant progeny; 25% of their offspring were new mutants and most
      of these were targeted gene replacements resulting from homologous recombination
      (HR) with a marked donor DNA. The procedure that generates these high frequencies
      relies on cleavage of the target by designed zinc-finger nucleases (ZFNs) and
      production of a linear donor in situ. Increased induction of ZFN expression led
      to higher frequencies of gene targeting, demonstrating the beneficial effect of
      activating the target. In the absence of a homologous donor DNA, ZFN cleavage led
      to the recovery of new mutants at three loci-y, ry and bw-through nonhomologous
      end joining (NHEJ) after cleavage. Because zinc fingers can be directed to a
      broad range of DNA sequences and targeting is very efficient, this approach
      promises to allow genetic manipulation of many different genes, even in cases
      where the mutant phenotype cannot be predicted.

PMID- 16452141
TI  - Coalescent processes when the distribution of offspring number among individuals
      is highly skewed.
AB  - We report a complex set of scaling relationships between mutation and
      reproduction in a simple model of a population. These follow from a consideration
      of patterns of genetic diversity in a sample of DNA sequences. Five different
      possible limit processes, each with a different scaled mutation parameter, can be
      used to describe genetic diversity in a large population. Only one of these
      corresponds to the usual population genetic model, and the others make
      drastically different predictions about genetic diversity. The complexity arises
      because individuals can potentially have very many offspring. To the extent that
      this occurs in a given species, our results imply that inferences from genetic
      data made under the usual assumptions are likely to be wrong. Our results also
      uncover a fundamental difference between populations in which generations are
      overlapping and those in which generations are discrete. We choose one of the
      five limit processes that appears to be appropriate for some marine organisms and
      use a sample of genetic data from a population of Pacific oysters to infer the
      parameters of the model. The data suggest the presence of rare reproduction
      events in which approximately 8% of the population is replaced by the offspring
      of a single individual.

PMID- 16452140
TI  - A functional module of yeast mediator that governs the dynamic range of heat
      shock gene expression.
AB  - We report the results of a genetic screen designed to identify transcriptional
      coregulators of yeast heat-shock factor (HSF). This sequence-specific activator
      is required to stimulate both basal and induced transcription; however, the
      identity of factors that collaborate with HSF in governing noninduced heat-shock
      gene expression is unknown. In an effort to identify these factors, we isolated
      spontaneous extragenic suppressors of hsp82-deltaHSE1, an allele of HSP82 that
      bears a 32-bp deletion of its high-affinity HSF-binding site, yet retains its two
      low-affinity HSF sites. Nearly 200 suppressors of the null phenotype of hsp82
      deltaHSE1 were isolated and characterized, and they sorted into six expression
      without heat-shock element (EWE) complementation groups. Strikingly, all six
      groups contain alleles of genes that encode subunits of Mediator. Three of the
      six subunits, Med7, Med10/Nut2, and Med21/Srb7, map to Mediator's middle domain;
      two subunits, Med14/Rgr1 and Med16/Sin4, to its tail domain; and one subunit,
      Med19/Rox3, to its head domain. Mutations in genes encoding these factors enhance
      not only the basal transcription of hsp82-deltaHSE1, but also that of wild-type
      heat-shock genes. In contrast to their effect on basal transcription, the more
      severe ewe mutations strongly reduce activated transcription, drastically
      diminishing the dynamic range of heat-shock gene expression. Notably, targeted
      deletion of other Mediator subunits, including the negative regulators
      Cdk8/Srb10, Med5/Nut1, and Med15/Gal11 fail to derepress hsp82-deltaHSE1. Taken
      together, our data suggest that the Ewe subunits constitute a distinct functional
      module within Mediator that modulates both basal and induced heat-shock gene
      transcription.

PMID- 16452143
TI  - Tracing nonlegume orthologs of legume genes required for nodulation and
      arbuscular mycorrhizal symbioses.
AB  - Most land plants can form a root symbiosis with arbuscular mycorrhizal (AM) fungi
      for assimilation of inorganic phosphate from the soil. In contrast, the nitrogen
      fixing root nodule symbiosis is almost completely restricted to the legumes. The
      finding that the two symbioses share common signaling components in legumes
      suggests that the evolutionarily younger nitrogen-fixing symbiosis has recruited
      functions from the more ancient AM symbiosis. The recent advances in cloning of
      the genes required for nodulation and AM symbioses from the two model legumes,
      Medicago truncatula and Lotus japonicus, provide a unique opportunity to address
      biological questions pertaining to the evolution of root symbioses in plants.
      Here, we report that nearly all cloned legume genes required for nodulation and
      AM symbioses have their putative orthologs in nonlegumes. The orthologous
      relationship can be clearly defined on the basis of both sequence similarity and
      microsyntenic relationship. The results presented here serve as a prelude to the
      comparative analysis of orthologous gene function between legumes and nonlegumes
      and facilitate our understanding of how gene functions and signaling pathways
      have evolved to generate species- or family-specific phenotypes.

PMID- 16452142
TI  - Functions of multiple exonucleases are essential for cell viability, DNA repair
      and homologous recombination in recD mutants of Escherichia coli.
AB  - Heterotrimeric RecBCD enzyme unwinds and resects a DNA duplex containing blunt
      double-stranded ends and directs loading of the strand-exchange protein RecA onto
      the unwound 3'-ending strand, thereby initiating the majority of recombination in
      wild-type Escherichia coli. When the enzyme lacks its RecD subunit, the resulting
      RecBC enzyme, active in recD mutants, is recombination proficient although it has
      only helicase and RecA loading activity and is not a nuclease. However, E. coli
      encodes for several other exonucleases that digest double-stranded and single
      stranded DNA and thus might act in consort with the RecBC enzyme to efficiently
      promote recombination reactions. To test this hypothesis, I inactivated multiple
      exonucleases (i.e., exonuclease I, exonuclease X, exonuclease VII, RecJ, and
      SbcCD) in recD derivatives of the wild-type and nuclease-deficient recB1067
      strain and assessed the ability of the resultant mutants to maintain cell
      viability and to promote DNA repair and homologous recombination. A complex
      pattern of overlapping and sometimes competing activities of multiple
      exonucleases in recD mutants was thus revealed. These exonucleases were shown to
      be essential for cell viability, DNA repair (of UV- and gamma-induced lesions),
      and homologous recombination (during Hfr conjugation and P1 transduction), which
      are dependent on the RecBC enzyme. A model for donor DNA processing in recD
      transconjugants and transductants was proposed.

PMID- 16452144
TI  - Saccharomyces cerevisiae polymerase zeta functions in mitochondria.
AB  - The MtArg8 reversion assay, which measures point mutation in mtDNA, indicates
      that in budding yeast Saccharomyces cerevisiae, DNA polymerase zeta and Rev1
      proteins participate in the mitochondrial DNA mutagenesis. Supporting this
      evidence, both polymerase zeta and Rev1p were found to be localized in the
      mitochondria. This is the first report demonstrating that the DNA polymerase zeta
      and Rev1 proteins function in the mitochondria.

PMID- 16452145
TI  - Dynamics of gene introgression in the African malaria vector Anopheles gambiae.
AB  - Anopheles gambiae is a major malaria vector in Africa and a popular model species
      for a variety of ecological, evolutionary, and genetic studies on vector control.
      Genetic manipulation of mosquito vectorial capacity is a promising new weapon for
      the control of malaria. However, the release of exotic transgenic mosquitoes will
      bring in novel alleles in addition to the parasite-inhibiting genes, which may
      have unknown effects on the local population. Therefore, it is necessary to
      develop methodologies that can be used to evaluate the spread rate of introduced
      genes in A. gambiae. In this study, the effects and dynamics of genetic
      introgression between two geographically distinct A. gambiae populations from
      western Kenya (Mbita) and eastern Tanzania (Ifakara) were investigated with
      amplified fragment length polymorphisms (AFLPs) and microsatellite markers.
      Microsatellites and polymorphic cDNA markers revealed a large genetic
      differentiation between the two populations (average F(ST) = 0.093, P < 0.001).
      When the two strains were crossed in random mating between the two populations,
      significant differences in the rate of genetic introgression were found in the
      mixed populations. Allele frequencies of 18 AFLP markers (64.3%) for Mbita and of
      26 markers (92.9%) for Ifakara varied significantly from F5 to F20. This study
      provides basic information on how a mosquito release program would alter the
      genetic makeup of natural populations, which is critical for pilot field testing
      and ecological risk evaluation of transgenic mosquitoes.

PMID- 16452146
TI  - Substitution mapping of dth1.1, a flowering-time quantitative trait locus (QTL)
      associated with transgressive variation in rice, reveals multiple sub-QTL.
AB  - A quantitative trait locus (QTL), dth1.1, was associated with transgressive
      variation for days to heading in an advanced backcross population derived from
      the Oryza sativa variety Jefferson and an accession of the wild rice relative
      Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O.
      rufipogon introgressions across the target region were constructed to dissect
      dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon
      parent, O. rufipogon alleles in the substitution lines caused early flowering
      under both short- and long-day lengths and provided evidence for at least two
      distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these
      sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and
      EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon
      introgressions in combination with dth1.1 alleles also detected an early
      flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and
      provided evidence for additional sub-QTL in the dth1.1 region. The availability
      of a series of near-isogenic lines with alleles introgressed from a wild relative
      of rice provides an opportunity to better understand the molecular basis of
      transgressive variation in a quantitative trait.

PMID- 16452147
TI  - In vivo analysis of a gain-of-function mutation in the Drosophila eag-encoded K+
      channel.
AB  - Neuronal Na+ and K+ channels elicit currents in opposing directions and thus have
      opposing effects on neuronal excitability. Mutations in genes encoding Na+ or K+
      channels often interact genetically, leading to either phenotypic suppression or
      enhancement for genes with opposing or similar effects on excitability,
      respectively. For example, the effects of mutations in Shaker (Sh), which encodes
      a K+ channel subunit, are suppressed by loss-of-function mutations in the Na+
      channel structural gene para, but enhanced by loss-of-function mutations in a
      second K+ channel encoded by eag. Here we identify two novel mutations that
      suppress the effects of a Sh mutation on behavior and neuronal excitability. We
      used recombination mapping to localize both mutations to the eag locus, and we
      used sequence analysis to determine that both mutations are caused by a single
      amino acid substitution (G297E) in the S2-S3 linker of Eag. Because these novel
      eag mutations confer opposite phenotypes to eag loss-of-function mutations, we
      suggest that eag(G297E) causes an eag gain-of-function phenotype. We hypothesize
      that the G297E substitution may cause premature, prolonged, or constitutive
      opening of the Eag channels by favoring the "unlocked" state of the channel.

PMID- 16452148
TI  - A linkage map for brown trout (Salmo trutta): chromosome homeologies and
      comparative genome organization with other salmonid fish.
AB  - We report on the construction of a linkage map for brown trout (Salmo trutta) and
      its comparison with those of other tetraploid-derivative fish in the family
      Salmonidae, including Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus
      mykiss), and Arctic char (Salvelinus alpinus). Overall, we identified 37 linkage
      groups (2n = 80) from the analysis of 288 microsatellite polymorphisms, 13
      allozyme markers, and phenotypic sex in four backcross families. Additionally, we
      used gene-centromere analysis to approximate the position of the centromere for
      20 linkage groups and thus relate linkage arrangements to the physical morphology
      of chromosomes. Sex-specific maps derived from multiple parents were estimated to
      cover 346.4 and 912.5 cM of the male and female genomes, respectively. As
      previously observed in other salmonids, recombination rates showed large sex
      differences (average female-to-male ratio was 6.4), with male crossovers
      generally localized toward the distal end of linkage groups. Putative homeologous
      regions inherited from the salmonid tetraploid ancestor were identified for 10
      pairs of linkage groups, including five chromosomes showing evidence of residual
      tetrasomy (pseudolinkage). Map alignments with orthologous regions in Atlantic
      salmon, rainbow trout, and Arctic char also revealed extensive conservation of
      syntenic blocks across species, which was generally consistent with chromosome
      divergence through Robertsonian translocations.

PMID- 16452149
TI  - Unique evolutionary mechanism in R-genes under the presence/absence polymorphism
      in Arabidopsis thaliana.
AB  - While the presence/absence polymorphism is commonly observed in disease
      resistance (R-) genes in Arabidopsis, only a few R-genes under the
      presence/absence polymorphism (R-P/A) have been investigated. To understand the
      mechanism of the molecular evolution of R-P/A, we investigated genetic variation
      of nine R-P/A in A. thaliana from worldwide populations. The number of possessed
      R-genes varied widely among accessions (two to nine, on average 4.3 +/-
      1.6/accession). No pair of accessions shared the same haplotype, and no clear
      geographic differentiation was observed with respect to the pattern of
      presence/absence of the R-genes investigated. Presence allele frequencies also
      varied among loci (25-70%), and no linkage disequilibrium was detected among
      them. Although the LRR region in regular R-genes is known to be highly
      polymorphic and has a high Ka/Ks ratio in A. thaliana, nucleotide sequences of
      this region in the R-P/A showed a relatively low level of genetic variation (pi =
      0.0002-0.016) and low Ka/Ks (0.03-0.70, <1). In contrast, the nucleotide
      diversities around the deletion junction of R-P/A were constantly high between
      presence and absence accessions for the R-genes (D(xy) = 0.031-0.103). Our
      results suggest that R-P/A loci evolved differently from other R-gene loci and
      that balancing selection plays an important role in molecular evolution of R-P/A.

PMID- 16452150
TI  - Mutations in the extra sex combs and Enhancer of Polycomb genes increase
      homologous recombination in somatic cells of Drosophila melanogaster.
AB  - We found that heterozygous mutant alleles of E(Pc) and esc increased homologous
      recombination from an allelic template in somatic cells in a P-element-induced
      double-strand break repair assay. Flies heterozygous for mutant alleles of these
      genes showed increased genome stability and decreased levels of apoptosis in
      imaginal discs and a concomitant increase in survival following ionizing
      radiation. We propose that this was caused by a genomewide increase in homologous
      recombination in somatic cells. A double mutant of E(Pc) and esc had no additive
      effect, showing that these genes act in the same pathway. Finally, we found that
      a heterozygous deficiency for the histone deacetylase, Rpd3, masked the radiation
      resistant phenotype of both esc and E(Pc) mutants. These findings provide
      evidence for a gene dosage-dependent interaction between the esc/E(z) complex and
      the Tip60 histone acetyltransferase complex. We propose that esc and E(Pc)
      mutants enhance homologous recombination by modulating the histone acetylation
      status of histone H4 at the double-strand break.

PMID- 16452151
TI  - A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled
      with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in
      Candida albicans.
AB  - TAC1, a Candida albicans transcription factor situated near the mating-type locus
      on chromosome 5, is necessary for the upregulation of the ABC-transporter genes
      CDR1 and CDR2, which mediate azole resistance. We showed previously the existence
      of both wild-type and hyperactive TAC1 alleles. Wild-type alleles mediate
      upregulation of CDR1 and CDR2 upon exposure to inducers such as fluphenazine,
      while hyperactive alleles result in constitutive high expression of CDR1 and
      CDR2. Here we recovered TAC1 alleles from two pairs of matched azole-susceptible
      (DSY294; FH1: heterozygous at mating-type locus) and azole-resistant isolates
      (DSY296; FH3: homozygous at mating-type locus). Two different TAC1 wild-type
      alleles were recovered from DSY294 (TAC1-3 and TAC1-4) while a single hyperactive
      allele (TAC1-5) was isolated from DSY296. A single amino acid (aa) difference
      between TAC1-4 and TAC1-5 (Asn977 to Asp or N977D) was observed in a region
      corresponding to the predicted activation domain of Tac1p. Two TAC1 alleles were
      recovered from FH1 (TAC1-6 and TAC1-7) and a single hyperactive allele (TAC1-7)
      was recovered from FH3. The N977D change was seen in TAC1-7 in addition to
      several other aa differences. The importance of N977D in conferring hyperactivity
      to TAC1 was confirmed by site-directed mutagenesis. Both hyperactive alleles TAC1
      5 and TAC1-7 were codominant with wild-type alleles and conferred hyperactive
      phenotypes only when homozygous. The mechanisms by which hyperactive alleles
      become homozygous was addressed by comparative genome hybridization and single
      nucleotide polymorphism arrays and indicated that loss of TAC1 heterozygosity can
      occur by recombination between portions of chromosome 5 or by chromosome 5
      duplication.

PMID- 16452153
TI  - The hitchhiking effect on linkage disequilibrium between linked neutral loci.
AB  - We analyzed a three-locus model of genetic hitchhiking with one locus
      experiencing positive directional selection and two partially linked neutral
      loci. Following the original hitchhiking approach by Maynard Smith and Haigh, our
      analysis is purely deterministic. In the first half of the selected phase after a
      favored mutation has entered the population, hitchhiking may lead to a strong
      increase of linkage disequilibrium (LD) between the two neutral sites if both are
      <0.1 s away from the selected site (where s is the selection coefficient). In the
      second half of the selected phase, the main effect of hitchhiking is to destroy
      LD. This occurs very quickly (before the end of the selected phase) when the
      selected site is between both neutral loci. This pattern cannot be attributed to
      the well-known variation-reducing effect of hitchhiking but is a consequence of
      secondary hitchhiking effects on the recombinants created in the selected phase.
      When the selected site is outside the neutral loci (which are, say, <0.1s apart),
      however, a fast decay of LD is observed only if the selected site is in the
      immediate neighborhood of one of the neutral sites (i.e., if the recombination
      rate r between the selected site and one of the neutral sites satisfies r<<0.1
      s). If the selected site is far away from the neutral sites (say, r > 0.3 s), the
      decay rate of LD approaches that of neutrality. Averaging over a uniform
      distribution of initial gamete frequencies shows that the expected LD at the end
      of the hitchhiking phase is driven toward zero, while the variance is increased
      when the selected site is well outside the two neutral sites. When the direction
      of LD is polarized with respect to the more common allele at each neutral site,
      hitchhiking creates more positive than negative linkage disequilibrium. Thus,
      hitchhiking may have a distinctively patterned LD-reducing effect, in particular
      near the target of selection.

PMID- 16452154
TI  - Do extracellular matrix protein expressions change with cyclic reproductive
      hormones in pelvic connective tissue from women with stress urinary incontinence?
AB  - BACKGROUND: To evaluate differential expression of transforming growth factor
      (TGF-beta1), latent transforming factor-binding proteins (LTBP-1, LTBP-2) and
      elastin microfibril components (fibrillin-1 and fibrillin-2) in vaginal tissue
      from women with stress urinary incontinence (SUI). METHODS: In this case-control
      study, vaginal tissue from women in both phases of the menstrual cycle was
      obtained. Messenger RNA (mRNA) expressions of LTBP-1, LTBP-2, fibrillin-1,
      fibrillin-2 and TGF-beta1 were determined by relative real-time quantification
      PCR. Tissue localization was analysed by immunohistochemistry, and
      semiquantitative protein expression was evaluated by Western blot analysis.
      RESULTS: Vaginal wall fibroblasts synthesized all proteins tested. LTBP-1, LTBP-2
      and TGF-beta1 co-localized with elastin microfibrils, fibrillin-1 and fibrillin-2
      in the extracellular matrix. LTBP-1 mRNA and protein expressions were higher in
      control versus women affected with SUI in the proliferative phase (P = 0.04),
      while in the secretory phase, mRNA expression in cases was higher (P = 0.04).
      Fibrillin-1 mRNA was higher in women affected by SUI versus controls in both
      phases, but no statistical differences in fibrillin-1 protein expression were
      observed between the two groups in either phase. LTBP-2 and TGF-beta1 mRNA
      expressions showed the same trends as LTBP-1. CONCLUSION: LTBP-1, LTBP-2, TGF
      beta1, fibrillin-1, and fibrillin-2 expressions are hormonally regulated in
      vaginal wall fibroblasts and differ in women affected by SUI when compared to
      controls. These data suggest a mechanism to regulate TGF-beta1 activity in pelvic
      connective tissue.

PMID- 16452152
TI  - De novo appearance and "strain" formation of yeast prion [PSI+] are regulated by
      the heat-shock transcription factor.
AB  - Yeast prions are non-Mendelian genetic elements that are conferred by altered and
      self-propagating protein conformations. Such a protein conformation-based
      transmission is similar to that of PrP(Sc), the infectious protein responsible
      for prion diseases. Despite recent progress in understanding the molecular nature
      and epigenetic transmission of prions, the underlying mechanisms governing prion
      conformational switch and determining prion "strains" are not understood. We
      report here that the evolutionarily conserved heat-shock transcription factor
      (HSF) strongly influences yeast prion formation and strain determination. An hsf1
      mutant lacking the amino-terminal activation domain inhibits the yeast prion
      [PSI+] formation whereas a mutant lacking the carboxyl-terminal activation domain
      promotes [PSI+] formation. Moreover, specific [PSI+] strains are preferentially
      formed in these mutants, demonstrating the importance of genetic makeup in
      determining de novo appearance of prion strains. Although these hsf1 mutants
      preferentially support the formation of certain [PSI+] strains, they are capable
      of receiving and faithfully propagating nonpreferable strains, suggesting that
      prion initiation and propagation are distinct processes requiring different
      cellular components. Our findings establish the importance of HSF in prion
      initiation and strain determination and imply a similar regulatory role of
      mammalian HSFs in the complex etiology of prion disease.

PMID- 16452155
TI  - Modulation of hepatocellular swelling-activated K+ currents by phosphoinositide
      pathway-dependent protein kinase C.
AB  - K(+) channels participate in the regulatory volume decrease (RVD) accompanying
      hepatocellular nutrient uptake and bile formation. We recently identified KCNQ1
      as a molecular candidate for a significant fraction of the hepatocellular
      swelling-activated K(+) current (I(KVol)). We have shown that the KCNQ1 inhibitor
      chromanol 293B significantly inhibited RVD-associated K(+) flux in isolated
      perfused rat liver and used patch-clamp techniques to define the signaling
      pathway linking swelling to I(KVol) activation. Patch-electrode dialysis of
      hepatocytes with solutions that maintain or increase phosphatidylinositol 4,5
      bisphosphate (PIP(2)) increased I(KVol), whereas conditions that decrease
      cellular PIP(2) decreased I(KVol). GTP and AlF(4)(-) stimulated I(KVol)
      development, suggesting a role for G proteins and phospholipase C (PLC).
      Supporting this, the PLC blocker U-73122 decreased I(KVol) and inhibited the
      stimulatory response to PIP(2) or GTP. Protein kinase C (PKC) is involved,
      because K(+) current was enhanced by 1-oleoyl-2-acetyl-sn-glycerol and inhibited
      after chronic PKC stimulation with phorbol 12-myristate 13-acetate (PMA) or the
      PKC inhibitor GF 109203X. Both I(KVol) and the accompanying membrane capacitance
      increase were blocked by cytochalasin D or GF 109203X. Acute PMA did not
      eliminate the cytochalasin D inhibition, suggesting that PKC-mediated I(KVol)
      activation involves the cytoskeleton. Under isotonic conditions, a slowly
      developing K(+) current similar to I(KVol) was activated by PIP(2), lipid
      phosphatase inhibitors to counter PIP(2) depletion, a PLC-coupled alpha(1)
      adrenoceptor agonist, or PKC activators and was depressed by PKC inhibition,
      suggesting that hypotonicity is one of a set of stimuli that can activate I(KVol)
      through a PIP(2)/PKC-dependent pathway. The results indicate that PIP(2)
      indirectly activates hepatocellular KCNQ1-like channels via cytoskeletal
      rearrangement involving PKC activation.

PMID- 16452156
TI  - Temperature dependence of human ether-a-go-go-related gene K+ currents.
AB  - The function of voltage-gated human ether-a-go-go related gene (hERG) K(+)
      channels is critical for both normal cardiac repolarization and suppression of
      arrhythmias initiated by premature excitation. These important functions are
      facilitated by their unusual kinetics that combine relatively slow activation and
      deactivation with rapid and voltage-dependent inactivation and recovery from
      inactivation. The thermodynamics of these unusual features were examined by
      exploring the effect of temperature on the activation and inactivation processes
      of hERG channels expressed in Chinese hamster ovary cells. Increased temperature
      shifted the voltage dependence of activation in the hyperpolarizing direction but
      that of inactivation in the depolarizing direction. This increases the relative
      occupancy of the open state and contributes to the marked temperature sensitivity
      of hERG current magnitude observed during action potential voltage clamps. The
      rates of activation and deactivation also increase with higher temperatures, but
      less markedly than do the rates of inactivation and recovery from inactivation.
      Our results also emphasize that one cannot extrapolate results obtained at room
      temperature to 37 degrees C by using a single temperature scale factor.

PMID- 16452157
TI  - Aortic smooth muscle and endothelial plasma membrane Ca2+ pump isoforms are
      inhibited differently by the extracellular inhibitor caloxin 1b1.
AB  - Plasma membrane Ca(2+) pumps (PMCA) that expel Ca(2+) from cells are encoded by
      four genes (PMCA1-4). In this study, we show that aortic endothelium and smooth
      muscle differ in their PMCA isoform mRNA expression: endothelium expressed
      predominantly PMCA1, and smooth muscle expressed PMCA4 and a lower level of
      PMCA1. In this study, we report a novel peptide (caloxin 1b1, obtained by
      screening for binding to extracellular domain 1 of PMCA4), which inhibited PMCA
      extracellularly, selectively, and had a higher affinity for PMCA4 than PMCA1. It
      inhibited the PMCA Ca(2+)-Mg(2+)-ATPase activity in leaky erythrocyte ghosts
      (mainly PMCA4) with a K(i) value of 46 +/- 5 microM, making it 10x more potent
      than the previously reported caloxin 2a1. It was isoform selective because it
      inhibited the PMCA1 Ca(2+)-Mg(2+)-ATPase in human embryonic kidney-293 cells with
      a higher K(i) value (105 +/- 11 microM) than for PMCA4. Caloxin 1b1 was selective
      in that it did not inhibit other ATPases. Because caloxin 1b1 had been selected
      to bind to an extracellular domain of PMCA, it could be added directly to cells
      and tissues to examine its effects on smooth muscle and endothelium. In de
      endothelialized aortic rings, caloxin 1b1 (200 microM) produced a contraction. It
      also increased the force of contraction produced by a submaximum concentration of
      phenylephrine. In aortic rings with endothelium intact, precontracted with
      phenylephrine and relaxed partially with a submaximum concentration of carbachol,
      caloxin 1b1 increased the force of contraction rather than potentiating the
      endothelium-dependent relaxation. In cultured cells, caloxin 1b1 increased the
      cytosolic [Ca(2+)] more in arterial smooth muscle cells than in endothelial
      cells. Thus caloxin 1b1 is the first highly selective extracellular PMCA
      inhibitor that works better on vascular smooth muscle than on endothelium.

PMID- 16452158
TI  - Dynamic biophysical strain modulates proinflammatory gene induction in meniscal
      fibrochondrocytes.
AB  - Fibrochondrocytes of meniscus adapt to changes in their biomechanical environment
      by mechanisms that are yet to be elucidated. In this study, the
      mechanoresponsiveness of fibrochondrocytes under normal and inflammatory
      conditions was investigated. Fibrochondrocytes from rat meniscus were exposed to
      dynamic tensile forces (DTF) at various magnitudes and frequencies. The
      mechanoresponsiveness was assessed by examining the expression of inducible
      nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), and matrix
      metalloproteinase-13 mRNA expression. The mRNA and protein analyses revealed that
      DTF at magnitudes of 5% to 20% did not induce proinflammatory gene expression. IL
      1beta induced a rapid increase in the iNOS mRNA. DTF strongly repressed IL-1beta
      dependent iNOS induction in a magnitude-dependent manner. Exposure to 15% DTF
      resulted in >90% suppression of IL-1beta-induced mRNA within 4 h and this
      suppression was sustained for the ensuing 20 h. The mechanosensitivity of
      fibrochondrocytes was also frequency dependent and maximal suppression of iNOS
      mRNA expression was observed at rapid frequencies of DTF compared with lower
      frequencies. Like iNOS, DTF also inhibited IL-1beta-induced expression of
      proinflammatory mediators involved in joint inflammation. The examination of
      temporal effects of DTF revealed that 4- or 8-h exposure of DTF was sufficient
      for its sustained anti-inflammatory effects during the next 20 or 16 h,
      respectively. Our findings indicate that mechanical signals act as potent anti
      inflammatory signals, where their magnitude and frequency are critical
      determinants of their actions. Furthermore, mechanical signals continue
      attenuating proinflammatory gene transcription for prolonged periods of time
      after their removal.

PMID- 16452159
TI  - Oncostatin M differentially regulates CXC chemokines in mouse cardiac
      fibroblasts.
AB  - Ischemia-reperfusion injury in the heart is characterized by marked infiltration
      of neutrophils in the myocardial interstitial space. Studies in human, canine,
      and murine models have revealed oncostatin M (OSM) expression in infiltrating
      leukocytes. In an effort to assess possible roles of OSM in the myocardium, we
      used cardiac fibroblasts (mCFs) isolated from adult mouse heart to determine
      whether recombinant murine OSM regulates the synthesis and release of MIP2/CXCL2,
      KC/CXCL1, and LIX/CXCL5, which are three potent neutrophil chemoattractants in
      the mouse. Our results demonstrate that mCFs express OSM receptors and that,
      within the IL-6 cytokine family, OSM uniquely induces significant release of KC
      and LIX in mCFs. In addition, although OSM activates the JAK-signal transducers
      and activators of transcription and MAPK pathways, we demonstrate that the OSM
      mediated CXC chemokine release in mCFs is also dependent on the activation of the
      phosphatidylinositol 3-kinase pathway.

PMID- 16452160
TI  - Multiple signaling pathways are involved in endothelin-1-induced brain
      endothelial cell migration.
AB  - We have observed that the vasoactive peptide endothelin-1 is a potent inducer of
      migration of primary human brain-derived microvascular endothelial cells. By
      blocking signal transduction pathways with specific inhibitors, and using
      dominant negative mutant infections, we have demonstrated that multiple pathways
      are involved in endothelin-1-induced migration. Absolutely required for migration
      are protein tyrosine kinase Src, Ras, protein kinase C (PKC),
      phosphatidylinositol 3-kinase, ERK, and JNK; partial requirements were exhibited
      by cAMP-activated protein kinase and p38 kinase. Partial elucidation of the
      signal transduction sequences showed that the MAPKs ERK, JNK, and p38 are
      positioned downstream of both PKC and cAMP-activated protein kinase in the signal
      transduction scheme. The results show that human brain endothelial cell migration
      has distinct characteristics, different from cells derived from other vascular
      beds, or from other species, often used as model systems. Furthermore, the
      results indicate that endothelin-1, secreted by many tumors, is an important
      contributor to tumor-produced proangiogenic microenvironment. This growth factor
      has been associated with increased microvessel density in tumors and is
      responsible for endothelial cell proliferation, migration, invasion, and tubule
      formation. Because many signal transduction pathways investigated in this study
      are potential or current targets for anti-angiogenesis therapy, these results are
      of critical importance for designing physiological antiangiogenic protocols.

PMID- 16452161
TI  - Albumin inhibits adipogenesis and stimulates cytokine release from human
      adipocytes.
AB  - Bovine serum albumin (BSA) is commonly used in adipocyte experiments as a binding
      protein for fat-soluble substances. Therefore, it is of interest to investigate
      whether BSA per se is influencing the functioning of human adipocytes in vitro.
      In the present study, we investigated the potential of BSA to affect the
      proliferation and differentiation capacity of human preadipocytes. BSA was found
      to inhibit adipose differentiation in a dose-dependent manner (being significant
      at concentrations of 2.5 microM), whereas proliferation was not affected. We
      further investigated the effect of BSA on the secretory function of adipocytes
      focusing on the release of selected cytokines. Preadipocytes and freshly isolated
      adipocytes incubated with BSA secreted significantly higher amounts of IL-6, -8,
      and -10, and TNF-alpha compared with cells incubated without BSA. The effects on
      cytokine secretion seemed to reside at the level of gene expression because BSA
      increased TNF-alpha and IL-6 mRNA in a dose-dependent manner. The results of the
      present study indicate that the presence of BSA in the culture medium has
      considerable effects on adipocyte function in vitro. These effects should be
      carefully considered for in vitro studies of adipose tissue.

PMID- 16452162
TI  - Paracrine signaling through the epithelial estrogen receptor alpha is required
      for proliferation and morphogenesis in the mammary gland.
AB  - Estradiol is a major regulator of postnatal mammary gland development and thought
      to exert its effects through estrogen receptor alpha (ERalpha) expressed in the
      mammary gland stroma and epithelium. Previous studies, however, were confounded
      by the use of an ERalpha mutant strain that retains some of the protein with
      transactivation activity. Here, we use an ERalpha-/- mouse strain in which no
      ERalpha transcript can be detected to analyze mammary gland development in the
      complete absence of ERalpha signaling. The ERalpha-/- females show no development
      beyond a rudimentary ductal system. By grafting ERalpha-/- epithelium or stroma
      in combination with ERalpha WT stroma or epithelium, we show that the primary
      target for estradiol is the mammary epithelium, whereas a direct response of the
      mammary stroma is not required for mammary gland development to proceed normally.
      Mammary glands reconstituted with ERalpha-/- mammary epithelium exposed to
      pregnancy hormones show increased transcription of milk protein genes, indicating
      that ERalpha signaling is not an absolute requirement for a transcriptional
      response to pregnancy hormones. When ERalpha-/- mammary epithelial cells are in
      close vicinity to ERalpha WT cells, they proliferate and contribute to all
      aspects of mammary gland development, indicating that estradiol, like
      progesterone, orchestrates proliferation and morphogenesis by a paracrine
      mechanism, affecting nearby cells in the mammary epithelium.

PMID- 16452163
TI  - Monitoring bacterial chemotaxis by using bioluminescence resonance energy
      transfer: absence of feedback from the flagellar motors.
AB  - We looked for a feedback system in Escherichia coli that might sense the
      rotational bias of flagellar motors and regulate the activity of the chemotaxis
      receptor kinase. Our search was based on the assumption that any machinery that
      senses rotational bias will be perturbed if flagellar rotation stops. We
      monitored the activity of the kinase in swimming cells by bioluminescence
      resonance energy transfer (BRET) between Renilla luciferase fused to the
      phosphatase, CheZ, and yellow fluorescent protein fused to the response
      regulator, CheY. Then we jammed the flagellar motors by adding an antifilament
      antibody that crosslinks adjacent filaments in flagellar bundles. At steady
      state, the rate of phosphorylation of CheY is equal to the rate of
      dephosphorylation of CheY-P, which is proportional to the degree of association
      between CheZ and CheY-P, the quantity sensed by BRET. No changes were observed,
      even upon addition of an amount of antibody that stopped the swimming of >95% of
      cells within a few seconds. So, the kinase does not appear to be sensitive to
      motor output. The BRET technique is complementary to one based on FRET, described
      previously. Its reliability was confirmed by measurements of the response of
      cells to the addition of attractants.

PMID- 16452164
TI  - Protein-protein interactions for cancer therapy.

PMID- 16452165
TI  - Dicer function is essential for lung epithelium morphogenesis.
AB  - DICER is a key enzyme that processes microRNA and small interfering RNA
      precursors into their short mature forms, enabling them to regulate gene
      expression. Only a single Dicer gene exists in the mouse genome, and it is
      broadly expressed in developing tissues. Dicer-null mutants die before
      gastrulation. Therefore, to study Dicer function in the later event of lung
      formation, we inactivated it in the mouse lung epithelium using a Dicer
      conditional allele and the Sonic Hedgehogcre (Shhcre) allele. Branching arrests
      in these mutant lungs, although epithelial growth continues in distal domains
      that are expanded compared with normal samples. These defects result in a few
      large epithelial pouches in the mutant lung instead of numerous fine branches
      present in a normal lung. Significantly, the initial phenotypes are apparent
      before an increase in epithelial cell death is observed, leading us to propose
      that Dicer plays a specific role in regulating lung epithelial morphogenesis
      independent of its requirement in cell survival. In addition, we found that the
      expression of Fgf10, a key gene involved in lung development, is up-regulated and
      expanded in the mesenchyme of Dicer mutant lungs. Previous studies support the
      hypothesis that precise localization of FGF10 in discrete sites of the lung
      mesenchyme serves as a chemoattractant for the outgrowth of epithelial branches.
      The aberrant Fgf10 expression may contribute to the Dicer morphological defects.
      However, the mechanism by which DICER functions in the epithelium to influence
      Fgf10 expression in the mesenchyme remains unknown.

PMID- 16452166
TI  - Links between alpha-catenin, NF-kappaB, and squamous cell carcinoma in skin.
AB  - Cancers display a diverse set of cellular defects, which are thought to be
      elicited by multiple genetic mutations. In this study, we show that when a single
      adherens junction protein, alpha-catenin, is removed by conditional targeting,
      the entire skin epidermis systematically transforms to a hyperproliferative,
      invasive tissue replete with inflammation. Transcriptional profiling and
      biochemical analyses reveal that alpha-catenin ablation is accompanied by
      activation of NF-kappaB and its proinflammatory target genes, along with genes
      involved in proliferation, wound healing, angiogenesis, and metastasis. Many of
      these alterations occur in vitro and in the embryo, and thus seem at least partly
      to be intrinsic to the loss of alpha-catenin. We show that reductions in alpha
      catenin, activation of NF-kappaB, and inflammation are common features of human
      squamous cell carcinomas of the skin.

PMID- 16452167
TI  - Nonsynchronous recovery of community characteristics in island spiders after a
      catastrophic hurricane.
AB  - We monitored spiders on 41 Bahamian islands for 4 years before and then 4 years
      after the catastrophic Hurricane Floyd passed directly over the site, inundating
      the study islands with its storm surge. The respective recoveries of major
      community properties after this annihilation were far from synchronous. Before
      the hurricane, the species-area relation was generally strong and the slope
      showed no temporal trend. After the hurricane, the slope increased from near zero
      (7 months later) to a value about equal to its prehurricane state. The lizard
      effect (difference in spider abundance or species richness between islands with
      and without the lizard Anolis sagrei) was generally strong before the hurricane;
      7 months after, the lizard effect on abundance was weak and the effect on
      richness had vanished. In subsequent years, the lizard effect on abundance became
      strong again, but the effect on species richness remained weak. The strength of
      the lizard effect on both abundance and richness over the 8 years was strongly
      positively related to the density of lizards measured on a subset of the study
      islands. Twelve months after the hurricane, species richness averaged over all
      islands rebounded to the last prehurricane value, but abundance attained only
      about half that value; this finding was remarkably similar to results found in an
      earlier study of spiders impacted by Hurricane Lili (1996) in a different
      Bahamian region. Nonetheless, in the next 3 years, species richness failed to
      increase further, part of its long-term decline at the study site.

PMID- 16452168
TI  - Roles of static and dynamic domains in stability and catalysis of adenylate
      kinase.
AB  - Protein dynamics, including conformational switching, are recognized to be
      crucial for the function of many systems. These motions are more challenging to
      study than simple static structures. Here, we present evidence suggesting that in
      the enzyme adenylate kinase large "hinge bending" motions closely related to
      catalysis are regulated by intrinsic properties of the moving domains and not by
      their hinges, by anchoring domains, or by remote allosteric-like regions. From a
      pair of highly homologous mesophilic and thermophilic adenylate kinases, we
      generated a series of chimeric enzymes using a previously undescribed method with
      synthetic genes. Subsequent analysis of the chimeras has revealed unexpected
      spatial separation of stability and activity control. Our results highlight
      specific contributions of dynamics to catalysis in adenylate kinase. Furthermore,
      the overall strategy and the specific mutagenesis method used in this study can
      be generally applied.

PMID- 16452170
TI  - Arsenic detoxification and evolution of trimethylarsine gas by a microbial
      arsenite S-adenosylmethionine methyltransferase.
AB  - In this article, a mechanism of arsenite [As(III)]resistance through methylation
      and subsequent volatization is described. Heterologous expression of arsM from
      Rhodopseudomonas palustris was shown to confer As(III) resistance to an arsenic
      sensitive strain of Escherichia coli. ArsM catalyzes the formation of a number of
      methylated intermediates from As(III), with trimethylarsine as the end product.
      The net result is loss of arsenic, from both the medium and the cells. Because
      ArsM homologues are widespread in nature, this microbial-mediated transformation
      is proposed to have an important impact on the global arsenic cycle.

PMID- 16452169
TI  - Crystal structure of human apolipoprotein A-I: insights into its protective
      effect against cardiovascular diseases.
AB  - Despite three decades of extensive studies on human apolipoprotein A-I (apoA-I),
      the major protein component in high-density lipoproteins, the molecular basis for
      its antiatherogenic function is elusive, in part because of lack of a structure
      of the full-length protein. We describe here the crystal structure of lipid-free
      apoA-I at 2.4 A. The structure shows that apoA-I is comprised of an N-terminal
      four-helix bundle and two C-terminal helices. The N-terminal domain plays a
      prominent role in maintaining its lipid-free conformation, indicating that
      mutants with truncations in this region form inadequate models for explaining
      functional properties of apoA-I. A model for transformation of the lipid-free
      conformation to the high-density lipoprotein-bound form follows from an analysis
      of solvent-accessible hydrophobic patches on the surface of the structure and
      their proximity to the hydrophobic core of the four-helix bundle. The crystal
      structure of human apoA-I displays a hitherto-unobserved array of positively and
      negatively charged areas on the surface. Positioning of the charged surface
      patches relative to hydrophobic regions near the C terminus of the protein offers
      insights into its interaction with cell-surface components of the reverse
      cholesterol transport pathway and antiatherogenic properties of this protein.
      This structure provides a much-needed structural template for exploration of
      molecular mechanisms by which human apoA-I ameliorates atherosclerosis and
      inflammatory diseases.

PMID- 16452171
TI  - Cohn's Crenothrix is a filamentous methane oxidizer with an unusual methane
      monooxygenase.
AB  - 135 years ago Ferdinand Cohn, the founder of bacteriology, microscopically
      observed a conspicuous filamentous bacterium with a complex life cycle and
      described it as Crenothrix polyspora. This uncultured bacterium is infamous for
      mass developments in drinking water systems, but its phylogeny and physiology
      remained unknown. We show that C. polyspora is a gammaproteobacterium closely
      related to methanotrophs and capable of oxidizing methane. We discovered that C.
      polyspora encodes a phylogenetically very unusual particulate methane
      monooxygenase whose expression is strongly increased in the presence of methane.
      Our findings demonstrate a previously unrecognized complexity of the evolutionary
      history and cell biology of methane-oxidizing bacteria.

PMID- 16452173
TI  - Prevalence and long-term significance of paraproteinaemia in rheumatoid
      arthritis.

PMID- 16452174
TI  - Germ line polymorphism in metastatic progression.
AB  - Somatic genetic analysis of tumors and metastases has yielded a plethora of
      information regarding genes associated with cancer progression. However, somatic
      alterations in tumor cells are only one source of variability. Genetic
      polymorphism may also play a significant role in person-to-person variability in
      metastasis frequency, raising the intriguing possibility that some individuals
      could be predisposed to secondary tumor development. The identification and
      characterization of these polymorphisms may have significant implications for the
      development of tailored treatment or prevention of recurrent disease.

PMID- 16452176
TI  - The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody
      therapy of experimental melanoma.
AB  - We examined the role of FcgammaR in antibody therapy of metastatic melanoma in
      wild-type and different FcgammaR knock-out mice. Treatment of B16F10-challenged
      wild-type mice with TA99 antibody specific for the gp75 tumor antigen resulted in
      a marked decrease in numbers of lung metastases. Treatment of individual FcgammaR
      knock-out mice revealed the high-affinity IgG receptor, FcgammaRI (CD64), to
      represent the central FcgammaR for TA99-induced antitumor effects. The potential
      of immune-modulating agents to further enhance the protective effect induced by
      monoclonal antibody (mAb) TA99 was examined in combination treatments consisting
      of mAb TA99 and a TLR-4 agonist, monophosphoryl lipid A (MPL). MPL did potently
      boost TA99 antibody-induced effects, and combination therapy was, again, found to
      be dependent on the presence of FcgammaRI.

PMID- 16452175
TI  - Counting heads in the war against cancer: defining the role of annexin A5 imaging
      in cancer treatment and surveillance.
AB  - The unveiling of the heterogeneous nature of cell death modes has compromised the
      long-lived consensus that cancer treatment typically kills cancer cells through
      apoptosis. Moreover, it implies that measures of apoptosis may be misleading
      indicators of treatment efficacy. Simultaneously, it has become clear that
      phosphatidylserine exposition, traditionally considered a hallmark of apoptosis,
      is also associated with most other cell death programs, rendering
      phosphatidylserine an attractive target for overall cell death imaging. Annexin
      A5 binds with strong affinity to phosphatidylserine and hence offers an
      interesting opportunity for visualization of aggregate cell death, thus providing
      a fit benchmark for in vivo monitoring of anticancer treatment. This might be of
      significant value for pharmacologic therapy development as well as clinical
      monitoring of treatment success.

PMID- 16452172
TI  - Drusen complement components C3a and C5a promote choroidal neovascularization.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in industrialized nations, affecting 30-50 million people worldwide.
      The earliest clinical hallmark of AMD is the presence of drusen, extracellular
      deposits that accumulate beneath the retinal pigmented epithelium. Although
      drusen nearly always precede and increase the risk of choroidal
      neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown
      whether drusen contribute to the development of CNV. Both in patients with AMD
      and in a recently described mouse model of AMD, early subretinal pigmented
      epithelium deposition of complement components C3 and C5 occurs, suggesting a
      contributing role for these inflammatory proteins in the development of AMD. Here
      we provide evidence that bioactive fragments of these complement components (C3a
      and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce
      VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a
      are generated early in the course of laser-induced CNV, an accelerated model of
      neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We
      also show that genetic ablation of receptors for C3a or C5a reduces VEGF
      expression, leukocyte recruitment, and CNV formation after laser injury, and that
      antibody-mediated neutralization of C3a or C5a or pharmacological blockade of
      their receptors also reduces CNV. Collectively, these findings establish a
      mechanistic basis for the clinical observation that drusen predispose to CNV,
      revealing a role for immunological phenomena in angiogenesis and providing
      therapeutic targets for AMD.

PMID- 16452177
TI  - Bone marrow-derived stromal cells express lineage-related messenger RNA species.
AB  - Evidence has emerged that bone marrow cells have a greater degree of plasticity
      than previously thought. However, there has been a call to establish proof that
      these bone marrow-derived cells function appropriately in their new environment.
      We have already shown that the bone marrow contributes to myofibroblasts in
      multiple organs and that this is exacerbated by injury and occurs in a mouse
      tumor model. Here, we provide evidence that these cells are functioning
      appropriately by showing that bone marrow-derived myofibroblasts are expressing
      mRNA for the alpha(1) chain of type I (pro)collagen using a new customized
      technique. This provides evidence that the bone marrow-tumor stroma axis is
      functionally relevant and may therefore subsequently be exploited to develop new
      strategies for anticancer therapy.

PMID- 16452178
TI  - Syrian hamster as a permissive immunocompetent animal model for the study of
      oncolytic adenovirus vectors.
AB  - Oncolytic adenoviruses represent an innovative approach to cancer therapy. These
      vectors are typically evaluated in immunodeficient mice with human xenograft
      tumors. However, in addition to being immunodeficient, this model is limited
      because normal and cancerous mouse tissues are poorly permissive for human
      adenovirus replication. This prompted us to search for a model that more
      accurately reflects the use of oncolytic adenoviruses in cancer patients. To this
      end, we developed a novel Syrian hamster model that is both immunocompetent and
      replication-permissive. We found that human adenovirus replicates well in Syrian
      hamster cell lines and confirmed replication in the lungs. Oncolytic adenovirus
      injection showed efficacy in three different hamster tumor models. Furthermore,
      i.t. oncolytic adenovirus injection resulted in suppression of primary and
      metastatic lesions, i.t. replication and necrosis, vector entrance into the
      bloodstream, replication in the liver and lungs, and anti-adenovirus antibody
      induction. Our findings show that the Syrian hamster is a promising
      immunocompetent model that is permissive to human adenovirus replication in
      tumors as well as normal tissues. Therefore, the Syrian hamster model may become
      a valuable tool for the field of oncolytic adenovirus vectors in which vector
      safety and efficacy can be evaluated.

PMID- 16452179
TI  - Rapid alteration of microRNA levels by histone deacetylase inhibition.
AB  - Improved understanding of the molecular mechanisms by which small-molecule
      inhibitors of histone deacetylases (HDAC) induce programs, such as cellular
      differentiation and apoptosis, would undoubtedly assist their clinical
      development as anticancer agents. As modulators of gene transcript levels, HDAC
      inhibitors (HDACi) typically affect only 5% to 10% of actively transcribed genes
      with approximately as many mRNA transcripts being up-regulated as down-regulated.
      Using microRNA (miRNA) array analysis, we report rapid alteration of miRNA levels
      in response to the potent hydroxamic acid HDACi LAQ824 in the breast cancer cell
      line SKBr3. Within 5 hours of exposure to a proapoptotic dose of LAQ824,
      significant changes were measured in 40% of the >60 different miRNA species
      expressed in SKBr3 cells with 22 miRNA species down-regulated and 5 miRNAs up
      regulated. To explore a potential functional link between HDACi induced mRNA up
      regulation and miRNA down-regulation, antisense experiments were done against miR
      27a and miR-27b, both abundantly expressed and down-regulated in SKBr3 cells by
      LAQ824. Correlating a set of genes previously determined by cDNA array analysis
      to be rapidly up-regulated by LAQ824 in SKBr3 with a database of potential 3'
      untranslated region miRNA binding elements, two genes containing putative miR-27
      anchor elements were identified as transcriptionally up-regulated following miR
      27 antisense transfection, ZBTB10/RINZF, a Sp1 repressor, and RYBP/DEDAF, an
      apoptotic facilitator. These findings emphasize the importance of post
      transcriptional mRNA regulation by HDACi in addition to their established effects
      on promoter-driven gene expression.

PMID- 16452180
TI  - Adenovirus-induced extracellular signal-regulated kinase phosphorylation during
      the late phase of infection enhances viral protein levels and virus progeny.
AB  - The Raf/mitogen-activated protein/extracellular signal-regulated kinase (ERK)
      kinase (MEK)/ERK signaling cascade enhances tumor cell proliferation in many
      cases. Here, we show that adenovirus type 5, a small DNA tumor virus used in
      experimental cancer therapy, strongly induces ERK phosphorylation during the late
      phase of infection. Pharmacologic inhibition of ERK phosphorylation reduced virus
      recovery by >100-fold. Blocking MEK/ERK signaling affected virus DNA replication
      and mRNA levels only weakly but strongly reduced the amount of viral proteins,
      independently of the kinases MNK1 and PKR. Hence, adenovirus induces the
      oncogenic Raf/MEK/ERK signaling pathway to enhance viral progeny by sustaining
      the levels of viral proteins. Concerning therapy, our results suggest that the
      use of Raf/MEK/ERK inhibitors will interfere with the propagation of oncolytic
      adenoviruses.

PMID- 16452181
TI  - The c-myc gene is a direct target of mammalian SWI/SNF-related complexes during
      differentiation-associated cell cycle arrest.
AB  - The activity of mammalian SWI/SNF-related chromatin remodeling complexes is
      crucial for differentiation, development, and tumor suppression. Cell cycle
      regulating activities dependent on the complexes include induction of the
      p21(WAF1/CIP1) kinase inhibitor and repression of E2F-responsive promoters. These
      responses are linked through effects on pRb phosphorylation, but the direct role
      of the SWI/SNF-related complexes in their regulation is not fully understood.
      Results presented here reveal that the complexes are required for regulation of a
      distinct pathway of proliferation control involving repression of c-myc
      expression in differentiating cells. This involves direct promoter targeting of
      the c-myc gene by the complexes. Induction of p21(WAF1/CIP1) is specifically
      dependent on prior repression of c-myc, but repression of E2F-responsive genes is
      dissociable from the regulation of c-myc and p21(WAF1/CIP1).

PMID- 16452182
TI  - Grg1 acts as a lung-specific oncogene in a transgenic mouse model.
AB  - Groucho proteins are transcriptional corepressors that are recruited to gene
      regulatory regions by numerous transcription factors. Long isoforms, such as
      Grg1, have all the domains of the prototype Drosophila Groucho. Short Groucho
      proteins, such as Grg5, have only the amino-terminal Q and G/P domains. We
      generated Grg1 and Grg5 transgenic mice and found that Grg1 overexpression
      induces lung adenocarcinoma, whereas Grg5 overexpression does not. Coexpression
      of Grg5 with Grg1 reduces tumor burden. Grg1 and Grg5 both diminish p53 protein
      levels; however, only Grg1 overexpression induces elevated levels of ErbB1 and
      ErbB2 receptor tyrosine kinases. The molecular and biological changes that
      accompany tumor progression in Grg1 transgenic mice closely reiterate events seen
      in human lung cancer. We also found that within a human lung tumor tissue array,
      a significant number of carcinomas overexpress Grg1/TLE1. Our data suggest that
      Grg1 overexpression contributes to malignancy in human lung cancers.

PMID- 16452183
TI  - PTEN loss promotes rasHa-mediated papillomatogenesis via dual up-regulation of
      AKT activity and cell cycle deregulation but malignant conversion proceeds via
      PTEN-associated pathways.
AB  - PTEN tumor suppressor gene failure in ras(Ha)-activated skin carcinogenesis was
      investigated by mating exon 5 floxed-PTEN (Delta5PTEN) mice to HK1.ras mice that
      expressed a RU486-inducible cre recombinase (K14.creP). PTEN inactivation in
      K14.cre/PTEN(flx/flx) keratinocytes resulted in epidermal
      hyperplasia/hyperkeratosis and novel 12-O-tetradecanoylphorbol-13-acetate (TPA)
      promoted papillomas, whereas HK1.ras/K14.cre/PTEN(flx/flx) cohorts displayed a
      rapid onset of papillomatogenesis due to a synergism of increased AKT activity
      and extracellular signal-regulated kinase (ERK) elevation. High 5-bromo-4
      deoxyuridine labeling in Delta5PTEN papillomas showed that a second promotion
      mechanism centered on failures in cell cycle control. Elevated cyclin D1 was
      associated with both HK1.ras/ERK- and Delta5PTEN-mediated AKT signaling, whereas
      cyclin E2 overexpression seemed dependent on PTEN loss. Spontaneous
      HK1.ras/Delta5PTEN malignant conversion was rare, whereas TPA promotion resulted
      in conversion with high frequency. On comparison with all previous HK1.ras
      carcinomas, such TPA-induced carcinomas expressed atypical retention of keratin
      K1 and lack of K13, a unique marker profile exhibited by TPA-induced
      K14.cre/PTEN(flx/flx) papillomas that also lacked endogenous c-ras(Ha)
      activation. Moreover, in all PTEN-null tumors, levels of ras(Ha)-associated total
      ERK protein became reduced, whereas phosphorylated ERK and cyclin D1 were lowered
      in late-stage papillomas returning to elevated levels, alongside increased cyclin
      E2 expression, in TPA-derived carcinomas. Thus, during early papillomatogenesis,
      PTEN loss promotes ras(Ha) initiation via elevation of AKT activity and
      synergistic failures in cyclin regulation. However, in progression, reduced
      ras(Ha)-associated ERK protein and activity, increased Delta5PTEN-associated
      cyclin E2 expression, and unique K1/K13 profiles following TPA treatment suggest
      that PTEN loss, rather than ras(Ha) activation, gives rise to a population of
      cells with greater malignant potential.

PMID- 16452184
TI  - Characterization of a von Hippel Lindau pathway involved in extracellular matrix
      remodeling, cell invasion, and angiogenesis.
AB  - Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene results in
      highly vascularized tumors, making the VHL tumor syndrome an ideal system to
      study the mechanisms of angiogenesis. VHL operates along two pathways with the
      first involving hypoxia-inducible factor-alpha degradation and down-regulation of
      its proangiogenic target genes vascular endothelial growth factor and platelet
      derived growth factor-beta, and the second pathway promoting extracellular matrix
      (ECM) assembly. Secretion of proangiogenic factors was shown to be a primary
      inducer of angiogenesis. Here, we show that loss of ECM assembly correlates with
      tumor angiogenesis in VHL disease. Upon inactivation of the VHL-ECM assembly
      pathway, we observe tumors that are highly vascularized, have a disrupted ECM,
      and show increased matrix metalloproteinase-2 activity. Loss of the VHL pathway
      leading to hypoxia-inducible factor-alpha degradation results in tumors with
      increased vascular endothelial growth factor levels but with surprisingly low
      microvessel density, a tightly assembled ECM and low invasive ability. We
      conclude that loss of ECM integrity could promote and maintain tumor angiogenesis
      by providing a route for blood vessels to infiltrate tumors.

PMID- 16452186
TI  - Delayed onset of Igf2-induced mammary tumors in Igf2r transgenic mice.
AB  - The insulin-like growth factor-II (IGF-II) receptor (IGF2R) regulates the level
      or activity of numerous proteins, including factors that control growth and
      differentiation. Frequent loss or inactivation of this receptor in a diverse
      group of tumors indicates that it may act as a tumor suppressor, but it is not
      known which functions of this receptor are selected against in the tumors.
      Lysosomal targeting and degradation of the growth-promoting IGF-II has been
      proposed as a mechanism for the tumor suppressor effects of IGF2R. As a genetic
      test of this hypothesis in vivo, we have produced Igf2r transgenic mice that
      ubiquitously express the transgene and have crossed these mice with mice that
      develop mammary tumors as a consequence of Igf2 overexpression. Our findings
      indicate that the presence of the Igf2r transgene delays mammary tumor onset and
      decreases tumor multiplicity in Igf2 transgenic mice. These findings are relevant
      to human tumors and preneoplastic conditions accompanied by altered IGF2
      expression.

PMID- 16452185
TI  - Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase
      pathway is involved in myostatin-regulated differentiation repression.
AB  - The cytokines of transforming growth factor beta (TGF-beta) and its superfamily
      members are potent regulators of tumorigenesis and multiple cellular events.
      Myostatin is a member of TGF-beta superfamily and plays a negative role in the
      control of cell proliferation and differentiation. We now show that myostatin
      rapidly activated the extracellular signal-regulated kinase 1/2 (Erk1/2) cascade
      in C2C12 myoblasts. A more remarkable Erk1/2 activation stimulated by myostatin
      was observed in differentiating cells than proliferating cells. The results also
      showed that Ras was the upstream regulator and participated in myostatin-induced
      Erk1/2 activation because the expression of a dominant-negative Ras prevented
      myostatin-mediated inhibition of Erk1/2 activation and proliferation.
      Importantly, the myostatin-suppressed myotube fusion and differentiation marker
      gene expression were attenuated by blockade of Erk1/2 mitogen-activated protein
      kinase (MAPK) pathway through pretreatment with MAPK/Erk kinase 1 (MEK1)
      inhibitor PD98059, indicating that myostatin-stimulated activation of Erk1/2
      negatively regulates myogenic differentiation. Activin receptor type IIb
      (ActRIIb) was previously suggested as the only type II membrane receptor
      triggering myostatin signaling. In this study, by using synthesized small
      interfering RNAs and dominant-negative ActRIIb, we show that myostatin failed to
      stimulate Erk1/2 phosphorylation and could not inhibit myoblast differentiation
      in ActRIIb-knockdown C2C12 cells, indicating that ActRIIb was required for
      myostatin-stimulated differentiation suppression. Altogether, our findings in
      this report provide the first evidence to reveal functional role of the Erk1/2
      MAPK pathway in myostatin action as a negative regulator of muscle cell growth.

PMID- 16452187
TI  - Urogenital carcinogenesis in female CD1 mice induced by in utero arsenic exposure
      is exacerbated by postnatal diethylstilbestrol treatment.
AB  - Transplacental inorganic arsenic carcinogenicity, together with postnatal
      exposure to diethylstilbestrol or tamoxifen, was studied. Pregnant CD1 mice
      received 85 ppm arsenic in the drinking water from gestation days 8 to 18 and
      were allowed to give birth. Groups (n = 35) of female offspring were injected
      s.c. on postpartum days 1 through 5 with diethylstilbestrol (2 microg/pup/d) or
      tamoxifen (10 microg/pup/d) and observed for 90 weeks. Arsenic alone induced some
      urogenital system tumors, including mostly benign tumors of the ovary and uterus,
      and adrenal adenoma. Diethylstilbestrol alone induced some tumors (primarily
      cervical) but when given after in utero arsenic, it greatly enhanced urogenital
      tumor incidence, multiplicity, and progression. For instance, compared with the
      incidence of urogenital malignancies in the control (0%), arsenic alone (9%), and
      diethylstilbestrol alone (21%) groups, arsenic plus diethylstilbestrol acted
      synergistically, inducing a 48% incidence of malignant urogenital tumors. Of the
      urogenital tumors induced by arsenic plus diethylstilbestrol, 80% were malignant,
      and 55% were multiple site. Arsenic plus diethylstilbestrol increased ovarian,
      uterine, and vaginal tumors, and urinary bladder proliferative lesions, including
      three transitional cell carcinomas. Tamoxifen alone did not increase urogenital
      tumors or affect arsenic-induced neoplasia but did increase arsenic-induced
      uroepithelial proliferative lesions. Uterine and bladder carcinoma induced by
      arsenic plus diethylstilbestrol greatly overexpressed estrogen receptor-alpha (ER
      alpha) and pS2, an estrogen-regulated gene. In neonatal uteri, prenatal arsenic
      increased ER-alpha expression and enhanced estrogen-related gene expression
      induced by postnatal diethylstilbestrol. Thus, arsenic acts with estrogens to
      enhance production of female mouse urogenital cancers.

PMID- 16452188
TI  - Cofactor of BRCA1: a novel transcription factor regulator in upper
      gastrointestinal adenocarcinomas.
AB  - Cofactor of BRCA1 (COBRA1) is a newly characterized member of the negative
      elongation factor (NELF) complex. In this work, we show that COBRA1 is
      overexpressed in the majority of primary upper gastrointestinal adenocarcinomas
      (UGC), and its overexpression correlates with down-regulation of TFF1. We have
      detected overexpression of COBRA1 mRNA using quantitative real-time reverse
      transcription-PCR in 28 (79%) primary UGCs. Immunohistochemical analysis of UGC
      tissue arrays that contained 70 tumor samples showed moderate-strong staining for
      COBRA1 in 60 (84%) tumors. Interestingly, the tumor samples showed absent-weak
      staining for TFF1 in 45 (65%) of the tumors. Simultaneous loss of TFF1 expression
      and overexpression of COBRA1 was observed in 42 of 70 (60%) tumors. Using small
      interfering RNA technology with gastric cancer cells, we have shown that COBRA1
      inhibition leads to increased TFF1 promoter activity and gene expression.
      Promoter analysis of TFF1 indicated that regulation of TFF1 by COBRA1 is estrogen
      independent in contrast to breast cancer. Moreover, COBRA1 regulation of TFF1 in
      gastric cancer cells was independent of NELF-E. Using several truncated mutants
      and site mutants of the TFF1 promoter, we have shown that COBRA1 can negatively
      regulate the activator protein-1 (AP-1) complex at the TFF1 promoter and thus
      down-regulate TFF1 expression in gastric cancer cell lines. Electrophoretic
      mobility shift assay showed that COBRA1 attenuates AP-1 binding to DNA. Our
      results suggest COBRA1 as a novel oncogene in UGCs that regulate AP-1 binding and
      the expression of TFF1 in upper gastric epithelia.

PMID- 16452189
TI  - Fibroblast growth factor 9 has oncogenic activity and is a downstream target of
      Wnt signaling in ovarian endometrioid adenocarcinomas.
AB  - Wnt signaling plays a key role in development and adult tissues via effects on
      cell proliferation, motility, and differentiation. The cellular response to Wnt
      ligands largely depends on their ability to stabilize beta-catenin and the
      ability of beta-catenin to bind and activate T-cell factor (TCF) transcription
      factors. Roughly 40% of ovarian endometrioid adenocarcinomas (OEA) have
      constitutive activation of Wnt signaling as a result of oncogenic mutations in
      the beta-catenin protein or inactivating mutations in key negative regulators of
      beta-catenin, such as the adenomatous polyposis coli and Axin tumor suppressor
      proteins. We used oligonucleotide microarrays to identify genes of which
      expression was activated in OEAs with beta-catenin dysregulation compared with
      OEAs lacking Wnt/beta-catenin pathway defects. Using microarray and quantitative
      PCR-based approaches, we found that fibroblast growth factor (FGF9) expression
      was increased >6-fold in primary OEAs with Wnt/beta-catenin pathway defects
      compared with OEAs lacking such defects. Evidence that beta-catenin and TCFs
      regulate FGF9 expression in several epithelial cell lines was obtained. We found
      FGF9 was mitogenic for epithelial cells and fibroblasts and FGF9 could stimulate
      invasion of epithelial and endothelial cells through Matrigel in transwell
      assays. Furthermore, FGF9 could promote neoplastic transformation of the E1A
      immortalized RK3E epithelial cell line, and short hairpin RNA-mediated inhibition
      of endogenous FGF9 expression in the OEA cell line TOV112D, which carries a beta
      catenin mutation, inhibited neoplastic growth properties of the cells. Our
      findings support the notion that FGF9 is a key factor contributing to the cancer
      phenotype of OEAs carrying Wnt/beta-catenin pathway defects.

PMID- 16452191
TI  - Mutational and epigenetic evidence for independent pathways for lung
      adenocarcinomas arising in smokers and never smokers.
AB  - Genetic and epigenetic alterations are considered to play important roles in lung
      cancer. Recent studies showed that EGFR and K-RAS mutations exhibited a mutually
      exclusive pattern in adenocarcinoma of the lung, suggesting the presence of two
      independent oncogenic pathways. However, it is unknown how epigenetic alterations
      were involved in lung carcinogenesis mediated by EGFR or K-RAS mutation. In this
      study, we examined the relationship between genetic and epigenetic alterations in
      164 cases of lung adenocarcinoma. Somatic mutations were determined by direct
      sequence of EGFR exons 18 to 21 and K-RAS codons 12 and 13. Methylation status of
      p16(INK4a), RASSF1A, APC, RARbeta, and CDH13, frequently methylated in lung
      cancer, was determined by methylation-specific PCR and the degree of methylation
      was defined as the methylation index. Multivariate analysis adjusted for age,
      sex, and smoking dose showed that the probability of having EGFR mutation was
      significantly lower among those with p16(INK4a) and CDH13 methylation than in
      those without [p16(INK4a): odds ratio (OR), 0.07; 95% confidence interval (95%
      CI), 0.02-0.33; CDH13: OR, 0.34; 95% CI, 0.15-0.77] and the methylation index was
      significantly lower in EGFR mutant cases than in wild type (OR, 0.70; 95% CI,
      0.52-0.95). By contrast, K-RAS mutation was significantly higher in p16(INK4a)
      methylated cases than in unmethylated cases (OR, 4.93; 95% CI, 1.54-15.7) and the
      methylation index was higher in K-RAS mutant cases than in wild type with
      marginal significance (OR, 1.46; 95% CI, 0.95-2.25). Our results indicate the
      differences in the evolvement of epigenetic alterations between the EGFR- and K
      RAS-mediated tumorigenesis and suggest the specific interaction of genetic and
      epigenetic changes in tumorigenesis of lung cancer.

PMID- 16452190
TI  - Transcriptional repression of telomerase RNA gene expression by c-Jun-NH2-kinase
      and Sp1/Sp3.
AB  - Telomerase is essential for immortalization of most human cancer cells.
      Expression of the core telomerase RNA (hTR) and reverse transcriptase (hTERT)
      subunits is mainly regulated by transcription. However, hTR transcriptional
      regulation remains poorly understood. We previously showed that the core hTR
      promoter is activated by Sp1 and is repressed by Sp3. Here, we show that the
      mitogen-activated protein kinase kinase kinase 1 (MEKK1)/c-Jun-NH(2)-kinase (JNK)
      pathway represses hTR expression by a mechanism that involves Sp1 and Sp3.
      Promoter activity was induced by the JNK inhibitor SP600125 and was repressed by
      activated MEKK1. Repression by MEKK1 was blocked by SP600125 or enhanced by
      coexpression of wild-type but not phosphoacceptor mutated JNK. SP600125 treatment
      also increased levels of endogenous hTR. Mutations in the hTR promoter Sp1/Sp3
      binding sites attenuated SP600125-mediated promoter induction, whereas
      coexpression of MEKK1 with Sp3 enhanced hTR promoter repression. Chromatin
      immunoprecipitation showed that levels of immunoreactive Sp1 associated with the
      hTR promoter were low in comparison with Sp3 in control cells but increased after
      JNK inhibition with a reciprocal decrease in Sp3 levels. No corresponding changes
      in Sp1/Sp3 protein levels were detected. Thus, JNK represses hTR promoter
      activity and expression, apparently by enhancing repression through Sp3.

PMID- 16452192
TI  - Protein chip discovery of secreted proteins regulated by the phosphatidylinositol
      3-kinase pathway in ovarian cancer cell lines.
AB  - Ovarian cancer has the highest mortality among the gynecologic malignancies. The
      phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated, leading to
      increased cell survival. This study aimed to identify secreted proteins regulated
      by the PI3K pathway in ovarian cancer cell lines. Surface-enhanced laser
      desorption-ionization time-of-flight mass spectrometry with cation-exchange
      protein-chips was used to analyze secreted proteins from five ovarian cancer cell
      lines (SKOV-3, PE01, OVCAR-3, OV167, and OV207). To activate the PI3K pathway,
      cells were treated with 50 ng/mL epidermal growth factor (EGF) with or without 10
      micromol/L LY294002, a PI3K inhibitor. Proteins induced by EGF and inhibited by
      LY294002, in the m/z range 7,500 to 9,500, were purified chromatographically,
      identified by peptide mass fingerprinting and NH(2)-terminal sequencing, and
      confirmed by immunodepletion. Two immunologically related proteins, m/z
      approximately 8,385 and 8,922, were identified as truncated and intact forms,
      respectively, of interleukin 8, a chemokine previously shown to be elevated in
      serum of ovarian cancer patients. Another protein, m/z 7,866, was identified as
      CXC chemokine ligand 1 (CXCL1) or GRO-alpha, a chemokine associated with melanoma
      formation and some epithelial cancers. EGF-stimulated CXCL1 levels were variably
      decreased by mitogen-activated protein kinase (MAPK)/extracellular signal
      regulated kinase kinase and p38 MAPK inhibition in the five cell lines, but only
      LY294002 fully reversed the EGF effect in all cell lines. Immunoreactive CXCL1
      levels in 160 conditioned media were highly correlated with corresponding peak
      intensities at m/z 7,866 by mass spectrometry, indicating the quantitative nature
      of these analyses. We conclude that proteomic analysis of cell models of human
      disease may facilitate the discovery of pathway-dependent proteins.

PMID- 16452193
TI  - GATA5 activation of the progesterone receptor gene promoter in breast cancer
      cells is influenced by the +331G/A polymorphism.
AB  - Previously, a modest association was observed between the progesterone receptor
      +331G/A gene variant and breast cancer risk. Here, in a larger sample of breast
      cancer cases and controls (n = 1,322/n = 1,953) nested in the Nurses' Health
      Study cohort, we confirm a significant association (odds ratio, 1.41; 95%
      confidence interval, 1.10-1.79) and suggest a molecular model. The association of
      the +331G/A variant with breast cancer was particularly strong among obese women
      (body mass index > 30; odds ratio, 2.87; 95% confidence interval, 1.40-5.90). To
      help understand the molecular mechanism by which this variant may predispose
      women to breast cancer, we identified nearby transcription factor binding sites.
      This search predicted a binding site for the GATA family of transcriptional
      regulators adjacent to this hPR polymorphism. Importantly, we found GATA3, GATA4,
      and GATA6 are expressed in normal breast tissue and two breast cancer cell lines,
      whereas GATA5 is minimally expressed in normal mammary tissue and more strongly
      expressed in two breast cancer cell lines. This finding was relevant because
      GATA5 bound the site adjacent to the +331G/A polymorphism, and activated the hPR
      (-711 to +822)-luciferase reporter plasmid in breast cancer cells. Overexpression
      of GATA5 increased expression of the endogenous hPR transcript, and GATA5 more
      strongly activated an hPR promoter construct encoding the PR-B isoform. Finally,
      hPR promoter constructs including the +331A were more strongly activated by GATA5
      than constructs including +331G. Our findings suggest that GATA5 interacts with
      the +331G/A polymorphism to stimulate hPR-B expression in mammary cells, which
      may contribute to breast cancer susceptibility.

PMID- 16452194
TI  - Ataxia telangiectasia mutated and checkpoint kinase 2 regulate BRCA1 to promote
      the fidelity of DNA end-joining.
AB  - Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are the two
      mechanisms responsible for repairing DNA double-strand breaks (DSBs) and act in
      either a collaborative or competitive manner in mammalian cells. DSB repaired by
      NHEJ may be more complicated than the simple joining of the ends of DSB, because,
      if nucleotides were lost, it would result in error-prone repair. This has led to
      the proposal that a subpathway of precise NHEJ exists that can repair DSBs with
      higher fidelity; this is supported by recent findings that the expression of the
      HR gene, BRCA1, is causally linked to in vitro and in vivo precise NHEJ activity.
      To further delineate this mechanism, the present study explored the connection
      between NHEJ and the cell-cycle checkpoint proteins, ataxia telangiectasia
      mutated (ATM) and checkpoint kinase 2 (Chk2), known to be involved in activating
      BRCA1, and tested the hypothesis that ATM and Chk2 promote precise end-joining by
      BRCA1. Support for this hypothesis came from the observations that (a) knockdown
      of ATM and Chk2 expression affected end-joining activity; (b) in BRCA1-defective
      cells, precise end-joining activity was not restored by a BRCA1 mutant lacking
      the site phosphorylated by Chk2 but was restored by wild-type BRCA1 or a mutant
      mimicking phosphorylation by Chk2; (c) Chk2 mutants lacking kinase activity or
      with a mutation at a site phosphorylated by ATM had a dominant negative effect on
      precise end-joining in BRCA1-expressing cells. These results suggest that the
      other two HR regulatory proteins, ATM and Chk2, act jointly to regulate the
      activity of BRCA1 in controlling the fidelity of DNA end-joining by precise NHEJ.

PMID- 16452195
TI  - Checkpoint kinase 2-mediated phosphorylation of BRCA1 regulates the fidelity of
      nonhomologous end-joining.
AB  - The tumor suppressor gene BRCA1 maintains genomic integrity by protecting cells
      from the deleterious effects of DNA double-strand breaks (DSBs). Through its
      interactions with the checkpoint kinase 2 (Chk2) kinase and Rad51, BRCA1 promotes
      homologous recombination, which is typically an error-free repair process. In
      addition, accumulating evidence implicates BRCA1 in the regulation of
      nonhomologous end-joining (NHEJ), which may involve precise religation of the DSB
      ends if they are compatible (i.e., error-free repair) or sequence alteration upon
      rejoining (i.e., error-prone or mutagenic repair). However, the precise role of
      BRCA1 in regulating these different subtypes of NHEJ is not clear. We provide
      here the genetic and biochemical evidence to show that BRCA1 promotes error-free
      rejoining of DSBs in human breast carcinoma cells while suppressing microhomology
      mediated error-prone end-joining and restricting sequence deletion at the break
      junction during repair. The repair spectrum in BRCA1-deficient cells was
      characterized by an increase in the formation of >2 kb deletions and in the usage
      of long microhomologies distal to the break site, compared with wild-type (WT)
      cells. This error-prone repair phenotype could also be revealed by disruption of
      the Chk2 phosphorylation site of BRCA1, or by expression of a dominant-negative
      kinase-dead Chk2 mutant in cells with WT BRCA1. We suggest that the differential
      control of NHEJ subprocesses by BRCA1, in concert with Chk2, reduces the
      mutagenic potential of NHEJ, thereby contributing to the prevention of familial
      breast cancers.

PMID- 16452196
TI  - An essential role of alternative splicing of c-myc suppressor FUSE-binding
      protein-interacting repressor in carcinogenesis.
AB  - Elevated expression of c-myc has been detected in a broad range of human cancers,
      indicating a key role for this oncogene in tumor development. Recently, an
      interaction between FUSE-binding protein-interacting repressor (FIR) and
      TFIIH/p89/XPB helicase was found to repress c-myc transcription and might be
      important for suppressing tumor formation. In this study, we showed that enforced
      expression of FIR induced apoptosis. Deletion of the NH(2)-terminal repression
      domain of FIR rescued the cells from apoptosis as did coexpression of c-Myc with
      FIR; thus, repression of Myc mediates FIR-driven apoptosis. Surprisingly, a
      splicing variant of FIR unable to repress c-myc or to drive apoptosis was
      frequently discovered in human primary colorectal cancers but not in the adjacent
      normal tissues. Coexpression of this splicing variant with repressor-competent
      FIR, either in HeLa cells or in the colon cancer cell line SW480, not only
      abrogated c-Myc suppression but also inhibited apoptosis. These results strongly
      suggest the expression of this splicing variant promotes tumor development by
      disabling FIR repression and sustaining high levels of c-Myc and opposing
      apoptosis in colorectal cancer.

PMID- 16452197
TI  - ErbB3-dependent motility and intravasation in breast cancer metastasis.
AB  - A better understanding of how epidermal growth factor receptor family members
      (ErbBs) contribute to metastasis is important for evaluating ErbB-directed
      therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation
      and motility. We find that increasing ErbB3-dependent signaling in orthotopic
      injection models of breast cancer can enhance intravasation and lung metastasis
      with no effect on primary tumor growth or microvessel density. Enhanced
      metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with
      stronger chemotaxis and invasion responses to heregulin beta1. Suppression of
      ErbB3 expression reduced both intravasation and metastasis. A human breast cancer
      tumor tissue microarray showed a significant association between ErbB3 and ErbB2
      expression and metastasis independent of tumor size. These results indicate that
      ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to
      metastasis through enhancing tumor cell invasion and intravasation in vivo and
      that ErbB-directed therapies may be useful for the inhibition of invasion
      independent of effects on tumor growth.

PMID- 16452198
TI  - Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces
      gene expression in prostate cancer.
AB  - Essential fatty acids are not only energy-rich molecules; they are also an
      important component of the membrane bilayer and recently have been implicated in
      induction of fatty acid synthase and other genes. Using gene chip analysis, we
      have found that arachidonic acid, an omega-6 fatty acid, induced 11 genes that
      are regulated by nuclear factor-kappaB (NF-kappaB). We verified gene induction by
      omega-6 fatty acid, including COX-2, IkappaBalpha, NF-kappaB, GM-CSF, IL-1beta,
      CXCL-1, TNF-alpha, IL-6, LTA, IL-8, PPARgamma, and ICAM-1, using quantitative
      reverse transcription-PCR. Prostaglandin E(2) (PGE(2)) synthesis was increased
      within 5 minutes of addition of arachidonic acid. Analysis of upstream signal
      transduction showed that within 5 minutes of fatty acid addition,
      phosphatidylinositol 3-kinase (PI3K) was significantly activated followed by
      activation of Akt at 30 minutes. Extracellular signal-regulated kinase 1 and 2,
      p38 and stress-activated protein kinase/c-Jun-NH(2)-kinase were not
      phosphorylated after omega-6 fatty acid addition. Thirty minutes after fatty acid
      addition, we found a significant 3-fold increase in translocation of NF-kappaB
      transcription factor to the nucleus. Addition of a nonsteroidal anti-inflammatory
      drug (NSAID) caused a decrease in COX-2 protein synthesis, PGE(2) synthesis, as
      well as inhibition of PI3K activation. We have previously shown that NSAIDs cause
      an inhibition of arachidonic acid-induced proliferation; here, we have shown that
      arachidonic acid-induced proliferation is also blocked (P < 0.001) by PI3K
      inhibitor LY294002. LY294002 also significantly inhibited the arachidonic acid
      induced gene expression of COX-2, IL-1beta, GM-CSF, and ICAM1. Taken together,
      the data suggest that arachidonic acid via conversion to PGE(2) plays an
      important role in stimulation of growth-related genes and proliferation via PI3K
      signaling and NF-kappaB translocation to the nucleus.

PMID- 16452199
TI  - Effect of inhibition of vascular endothelial growth factor signaling on
      distribution of extravasated antibodies in tumors.
AB  - Antibodies and other macromolecular therapeutics can gain access to tumor cells
      via leaky tumor vessels. Inhibition of vascular endothelial growth factor (VEGF)
      signaling can reduce the vascularity of tumors and leakiness of surviving
      vessels, but little is known about how these changes affect the distribution of
      antibodies within tumors. We addressed this issue by examining the distribution
      of extravasated antibodies in islet cell tumors of RIP-Tag2 transgenic mice and
      implanted Lewis lung carcinomas using fluorescence and confocal microscopic
      imaging. Extravasated nonspecific immunoglobulin G (IgG) and antibodies to fibrin
      or E-cadherin accumulated in irregular patchy regions of stroma. Fibrin also
      accumulated in these regions. Anti-E-cadherin antibody, which targets epitopes on
      tumor cells of RIP-Tag2 adenomas, was the only antibody to achieve detectable
      levels within tumor cell clusters at 6 hours after i.v. injection. Treatment for
      7 days with AG-013736, a potent inhibitor of VEGF signaling, reduced the tumor
      vascularity by 86%. The overall area density of extravasated IgG/antibodies
      decreased after treatment but the change was less than the reduction in
      vascularity and actually increased when expressed per surviving tumor vessel.
      Accumulation of anti-E-cadherin antibody in tumor cell clusters was similarly
      affected. The patchy pattern of antibodies in stroma after treatment
      qualitatively resembled untreated tumors and surprisingly coincided with sleeves
      of basement membrane left behind after pruning of tumor vessels. Together, the
      findings suggest that antibody transport increases from surviving tumor vessels
      after normalization by inhibition of VEGF signaling. Basement membrane sleeves
      may facilitate this transport. Antibodies preferentially distribute to tumor
      stroma but also accumulate on tumor cells if binding sites are accessible.

PMID- 16452200
TI  - Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and
      suppress apoptosis in breast cancer cells.
AB  - Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor-3
      (VEGFR-3) are protein tyrosine kinases that are overexpressed in human cancer and
      play an important role in survival signaling. In addition to its involvement with
      cell survival, VEGFR-3 is a primary factor in lymphatic angiogenesis. Because FAK
      function is regulated by its COOH terminus (FAK-CD), we used FAK-CD as a target
      to identify binding partners. We isolated a peptide from a phage library that
      bound to FAK-CD, specifically the focal adhesion targeting domain of FAK and was
      homologous to VEGFR-3, suggesting these two tyrosine kinases physically interact.
      We have also shown that VEGFR-3 is overexpressed in human breast tumors and
      cancer cell lines. For the first time, we have shown the physical association of
      FAK and VEGFR-3. The association between the NH(2) terminus of VEGFR-3,
      containing the peptide identified by phage display, and the COOH terminus of FAK
      was detected by in vitro and in vivo binding studies. We then coupled a 12-amino
      acid VEGFR-3 peptide, AV3, to a TAT cellular penetration sequence and showed that
      AV3 and not control-scrambled peptide caused specific displacement of FAK from
      the focal adhesions and affected colocalization of FAK and VEGFR-3. In addition,
      AV3 peptide decreased proliferation and caused cell detachment and apoptosis in
      breast cancer cell lines but not in normal breast cells. Thus, the FAK/VEGFR-3
      interaction may have a potential use to develop novel molecular therapeutics to
      target the signaling between FAK and VEGFR-3 in human tumors.

PMID- 16452201
TI  - Heparanase induces vascular endothelial growth factor expression: correlation
      with p38 phosphorylation levels and Src activation.
AB  - Heparanase is an endo-beta-D-glucuronidase involved in cleavage of heparan
      sulfate moieties and hence participates in extracellular matrix (ECM) degradation
      and remodeling. Traditionally, heparanase activity was correlated with the
      metastatic potential of a variety of tumor-derived cell types. Cloning of the
      heparanase gene indicated that heparanase expression is up-regulated in a variety
      of primary human tumors. In some cases, heparanase up-regulation correlated with
      increased tumor vascularity, an angiogenic feature that could be recapitulated in
      a number of in vitro and in vivo models. The mechanism by which heparanase
      enhances angiogenic responses is not entirely clear but is thought to be mediated
      primarily by release of ECM-resident angiogenic growth factors such as basic
      fibroblast growth factor and vascular endothelial growth factor (VEGF). Here, we
      examined the possibility that heparanase directly participates in VEGF gene
      regulation. We provide evidence that heparanase overexpression in human embryonic
      kidney 293, MDA-MB-435 human breast carcinoma, and rat C6 glioma cells resulted
      in a 3- to 6-fold increase in VEGF protein and mRNA levels, which correlated with
      elevation of p38 phosphorylation. Moreover, heparanase down-regulation in B16
      mouse melanoma cells by a specific siRNA vector was accompanied by a decrease in
      VEGF and p38 phosphorylation levels, suggesting that VEGF gene expression is
      regulated by endogenous heparanase. Interestingly, a specific p38 inhibitor did
      not attenuate VEGF up-regulation by heparanase whereas Src inhibitors completely
      abrogated this effect. These results indicate, for the first time, that
      heparanase is actively involved in the regulation of VEGF gene expression,
      mediated by activation of Src family members.

PMID- 16452202
TI  - Isolation of a natural inhibitor of human malignant glial cell invasion: inter
      alpha-trypsin inhibitor heavy chain 2.
AB  - Malignant central nervous system (CNS) tumors, such as glioblastoma multiforme,
      invade the brain and disrupt normal tissue architecture, making complete surgical
      removal virtually impossible. Here, we have developed and optimized a
      purification strategy to isolate and identify natural inhibitors of glioma cell
      invasion in a three-dimensional collagen type I matrix. Inter alpha-trypsin
      inhibitor heavy chain 2 (ITI H2) was identified from the most inhibitory
      fractions and its presence was confirmed both as a single protein and in a
      bikunin-bound form. Stable overexpression in U251 glioma cells validated ITI H2's
      strong inhibition of human glioma cell invasion together with significant
      inhibition of cell proliferation and promotion of cell-cell adhesion. Analysis of
      primary human brain tumors showed significantly higher levels of ITI H2 in normal
      brain and low-grade tumors compared with high-grade gliomas, indicating an
      inverse correlation with malignancy. The phosphatidylinositol 3-kinase/Akt
      signaling cascade seemed to be one of the pathways involved in the effect of ITI
      H2 on U251 cells. These findings suggest that reduction of ITI H2 expression
      correlates with brain tumor progression and that targeting factors responsible
      for its loss or restoring the ITI supply exogenously may serve as potential
      therapeutic strategies for a variety of CNS tumors.

PMID- 16452203
TI  - Human lymphoblastoid proteome analysis reveals a role for the inhibitor of
      acetyltransferases complex in DNA double-strand break response.
AB  - A DNA double-strand break (DSB) is highly cytotoxic; it emerges as the type of
      DNA damage that most severely affects the genomic integrity of the cell. It is
      essential that DNA DSBs are recognized and repaired efficiently, in particular,
      prior to mitosis, to prevent genomic instability and eventually, the development
      of cancer. To assess the pathways that are induced on DNA DSBs, 14 human
      lymphoblastoid cell lines were challenged with bleomycin for 30 and 240 minutes
      to establish the fast and more prolonged response, respectively. The proteomes of
      14 lymphoblastoid cell lines were investigated to account for the variation among
      individuals. The primary DNA DSB response was expected to occur within the
      nucleus; therefore, the nuclear extracts were considered. Differential analysis
      was done using two-dimensional difference in gel electrophoresis; paired ANOVA
      statistics were used to recognize significant changes in time. Many proteins
      whose nuclear levels changed statistically significantly showed a fast response,
      i.e., within 30 minutes after bleomycin challenge. A significant number of these
      proteins could be assigned to known DNA DSB response processes, such as sensing
      DSBs (Ku70), DNA repair through effectors (high-mobility group protein 1), or
      cell cycle arrest at the G(2)-M phase checkpoint (14-3-3 zeta). Interestingly,
      the nuclear levels of all three proteins in the INHAT complex were reduced after
      30 minutes of bleomycin challenge, suggesting that this complex may have a role
      in changing the chromatin structure, allowing the DNA repair enzymes to gain
      access to the DNA lesions.

PMID- 16452204
TI  - Ectopic activity of fibroblast growth factor receptor 1 in hepatocytes
      accelerates hepatocarcinogenesis by driving proliferation and vascular
      endothelial growth factor-induced angiogenesis.
AB  - Fibroblast growth factor (FGF) signaling mediates cell-to-cell communication in
      development and organ homeostasis in adults. Of the four FGF receptor (FGFR)
      tyrosine kinases, only FGFR4 is expressed in mature hepatocytes. Although FGFR1
      is expressed by hepatic cell progenitors and adult nonparenchymal cells, ectopic
      expression is commonly observed in hepatoma cells. Here, we determined whether
      ectopic FGFR1 is a cause or consequence of hepatocellular carcinoma by targeting
      a constitutively active human FGFR1 to mouse hepatocytes. Livers of transgenic
      mice exhibited accelerated regeneration after partial hepatectomy but no signs of
      neoplastic or preneoplastic abnormalities for up to 18 months. However, in
      diethylnitrosamine-treated mice, the chronic FGFR1 activity promoted an incidence
      of 44% adenomas at 4 months and 38% hepatocellular carcinoma at 8 months. No
      adenoma or hepatocellular carcinoma was observed in diethylnitrosamine-treated
      wild-type (WT) livers at 4 or 8 months, respectively. At 10 and 12 months, tumor
      bearing livers in transgenic mice were twice the size of those in WT animals.
      Isolated hepatoma cells from the transgenic tumors exhibited a growth advantage
      in culture. Advanced hepatocellular carcinoma in the transgenic livers exhibited
      a reduced rate of necrosis. This was accompanied by a mean microvessel density of
      2.7 times that of WT tumors and a markedly higher level of vascular endothelial
      growth factor. In cooperation with an initiator, the persistent activity of
      ectopic FGFR1 in hepatocytes is a strong promoter of hepatocellular carcinoma by
      driving cell proliferation at early stages and promoting neoangiogenesis at late
      stages of progression.

PMID- 16452205
TI  - Autocrine production of interleukin-4 and interleukin-10 is required for survival
      and growth of thyroid cancer cells.
AB  - Although CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass
      does not seem to be affected by such expression. We have recently shown that
      thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance
      to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly
      purified thyroid cancer cells were completely refractory to CD95-induced
      apoptosis despite the consistent expression of Fas-associated death domain and
      caspase-8. The analysis of potential molecules able to prevent caspase-8
      activation in thyroid cancer cells revealed a remarkable up-regulation of
      cellular FLIP(L) (cFLIP(L)) and PED/PEA-15, two antiapoptotic proteins whose
      exogenous expression in normal thyrocytes inhibited the death-inducing signaling
      complex of CD95. Additionally, small interfering RNA FLIP and PED antisense
      sensitized thyroid cancer cells to CD95-mediated apoptosis. Exposure of normal
      thyrocytes to IL-4 and IL-10 potently up-regulated cFLIP and PED/PEA-15,
      suggesting that these cytokines are responsible for thyroid cancer cell
      resistance to CD95 stimulation. Moreover, treatment with neutralizing antibodies
      against IL-4 and IL-10 or exogenous expression of suppressor of cytokine
      signaling-1 of thyroid cancer cells resulted in cFLIP and PED/PEA-15 down
      regulation and CD95 sensitization. More importantly, prolonged IL-4 and IL-10
      neutralization induced cancer cell growth inhibition and apoptosis, which were
      prevented by blocking antibodies against CD95 ligand. Altogether, autocrine
      production of IL-4 and IL-10 neutralizes CD95-generated signals and allows
      survival and growth of thyroid cancer cells. Thus, IL-4 and IL-10 may represent
      key targets for the treatment of thyroid cancer.

PMID- 16452206
TI  - mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates
      Akt.
AB  - Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor
      activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic
      cellular effects including an mTOR-dependent loss in insulin receptor substrate-1
      expression leading to feedback down-regulation of signaling through the pathway.
      In model systems, tumors exhibiting mutational activation of phosphoinositide-3
      kinase/Akt kinase, a common event in cancers, are hypersensitive to mTOR
      inhibitors, including rapamycin. Despite the activity in model systems, in
      patients, mTOR inhibitors exhibit more modest antitumor activity. We now show
      that mTOR inhibition induces insulin receptor substrate-1 expression and
      abrogates feedback inhibition of the pathway, resulting in Akt activation both in
      cancer cell lines and in patient tumors treated with the rapamycin derivative,
      RAD001. IGF-I receptor inhibition prevents rapamycin-induced Akt activation and
      sensitizes tumor cells to inhibition of mTOR. In contrast, IGF-I reverses the
      antiproliferative effects of rapamycin in serum-free medium. The data suggest
      that feedback down-regulation of receptor tyrosine kinase signaling is a frequent
      event in tumor cells with constitutive mTOR activation. Reversal of this feedback
      loop by rapamycin may attenuate its therapeutic effects, whereas combination
      therapy that ablates mTOR function and prevents Akt activation may have improved
      antitumor activity.

PMID- 16452208
TI  - Aberrant activation of notch signaling in human breast cancer.
AB  - A role for Notch signaling in human breast cancer has been suggested by both the
      development of adenocarcinomas in the murine mammary gland following pathway
      activation and the loss of Numb expression, a negative regulator of the Notch
      pathway, in a large proportion of breast carcinomas. However, it is not clear
      currently whether Notch signaling is frequently activated in breast tumors, and
      how it causes cellular transformation. Here, we show accumulation of the
      intracellular domain of Notch1 and hence increased Notch signaling in a wide
      variety of human breast carcinomas. In addition, we show that increased RBP
      Jkappa-dependent Notch signaling is sufficient to transform normal breast
      epithelial cells and that the mechanism of transformation is most likely through
      the suppression of apoptosis. More significantly, we show that attenuation of
      Notch signaling reverts the transformed phenotype of human breast cancer cell
      lines, suggesting that inhibition of Notch signaling may be a therapeutic
      strategy for this disease.

PMID- 16452207
TI  - Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1:
      implications for tumor progression and metastasis.
AB  - Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1- and tumor
      necrosis factor alpha (TNF-alpha)-inducible transcript in primary human fetal
      astrocytes by a rapid subtraction hybridization approach. Interestingly, AEG-1
      expression is elevated in subsets of breast cancer, glioblastoma multiforme and
      melanoma cells and AEG-1 cooperates with Ha-ras to promote transformation of
      immortalized melanocytes. Activation of the transcription factor nuclear factor
      kappaB (NF-kappaB), a TNF-alpha downstream signaling component, is associated
      with several human illnesses, including cancer, and NF-kappaB controls the
      expression of multiple genes involved in tumor progression and metastasis. We now
      document that AEG-1 is a significant positive regulator of NF-kappaB. Enhanced
      expression of AEG-1 via a replication-incompetent adenovirus (Ad.AEG-1) in HeLa
      cells markedly increased binding of the transcriptional activator p50/p65 complex
      of NF-kappaB. The NF-kappaB activation induced by AEG-1 corresponded with
      degradation of IkappaBalpha and nuclear translocation of p65 that resulted in the
      induction of NF-kappaB downstream genes. Infection with an adenovirus expressing
      the mt32IkappaBalpha superrepressor (Ad.IkappaBalpha-mt32), which prevents p65
      nuclear translocation, inhibited AEG-1-induced enhanced agar cloning efficiency
      and increased matrigel invasion of HeLa cells. We also document that TNF-alpha
      treatment resulted in nuclear translocation of both AEG-1 and p65 wherein these
      two proteins physically interacted, suggesting a potential mechanism by which AEG
      1 could activate NF-kappaB. Our findings suggest that activation of NF-kappaB by
      AEG-1 could represent a key molecular mechanism by which AEG-1 promotes anchorage
      independent growth and invasion, two central features of the neoplastic
      phenotype.

PMID- 16452210
TI  - L-selectin facilitation of metastasis involves temporal induction of Fut7
      dependent ligands at sites of tumor cell arrest.
AB  - Hematogenous carcinoma metastasis is supported by aggregated platelets and
      leukocytes, forming tumor cell emboli. Early tumor cell-platelet interactions can
      be mediated by P-selectin binding to tumor cell surface ligands and this process
      is blocked by heparin. We previously showed that L-selectin deficiency also
      attenuates experimental metastasis. However, the mechanisms and timing of L
      selectin action remained unknown. Here, we study how L-selectin facilitates
      establishment of pulmonary metastatic foci in syngeneic mice by using
      experimental metastasis to time events following entry of tumor cells into the
      bloodstream. Although L-selectin deficiency did not affect platelet aggregation
      or initial tumor cell embolization, the association of leukocytes with tumor
      cells was reduced and tumor cell survival was diminished 24 hours later. Temporal
      inhibition of L-selectin by a function-blocking antibody reduced metastasis.
      Moreover, although selectin blockade by heparin 6 to 18 hours after tumor cell
      injection was synergistic with P-selectin deficiency in reducing metastasis,
      there was no further effect in L-selectin-deficient animals. Thus, heparin
      apparently works at these time points primarily by blocking L-selectin.
      Endogenous L-selectin ligands were concomitantly induced adjacent to established
      intravascular tumor cell emboli in a similar time window when leukocytes were
      also present. Metastasis was attenuated in mice missing these induced endogenous
      L-selectin ligands due to fucosyltransferase-7 deficiency. Thus, L-selectin
      facilitation of metastasis progression involves leukocyte-endothelial
      interactions at sites of intravascular arrest supported by local induction of L
      selectin ligands via fucosyltransferase-7. These data provide the first
      explanation for how leukocyte L-selectin facilitates tumor metastasis.

PMID- 16452209
TI  - Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells,
      inhibits growth, and distinguishes malignant from normal phenotype in three
      dimensional cultures and in vivo.
AB  - Current therapeutic approaches to cancer are designed to target molecules that
      contribute to malignant behavior but leave normal tissues intact. beta(1)
      integrin is a candidate target well known for mediating cell-extracellular matrix
      (ECM) interactions that influence diverse cellular functions; its aberrant
      expression has been implicated in breast cancer progression and resistance to
      cytotoxic therapy. The addition of beta(1) integrin inhibitory agents to breast
      cancer cells at a single-cell stage in a laminin-rich ECM (three-dimensional
      lrECM) culture was shown to down-modulate beta(1) integrin signaling, resulting
      in malignant reversion. To investigate beta(1) integrin as a therapeutic target,
      we modified the three-dimensional lrECM protocol to approximate the clinical
      situation: before treatment, we allowed nonmalignant cells to form organized
      acinar structures and malignant cells to form tumor-like colonies. We then tested
      the ability of beta(1) integrin inhibitory antibody, AIIB2, to inhibit tumor cell
      growth in several breast cancer cell lines (T4-2, MDA-MB-231, BT474, SKBR3, and
      MCF-7) and one nonmalignant cell line (S-1). We show that beta(1) integrin
      inhibition resulted in a significant loss of cancer cells, associated with a
      decrease in proliferation and increase in apoptosis, and a global change in the
      composition of residual colonies. In contrast, nonmalignant cells that formed
      tissue-like structures remained resistant. Moreover, these cancer cell-specific
      antiproliferative and proapoptotic effects were confirmed in vivo with no
      discernible toxicity to animals. Our findings indicate that beta(1) integrin is a
      promising therapeutic target, and that the three-dimensional lrECM culture assay
      can be used to effectively distinguish malignant and normal tissue response to
      therapy.

PMID- 16452211
TI  - SRC uses Cas to suppress Fhl1 in order to promote nonanchored growth and
      migration of tumor cells.
AB  - Anchorage independence and motility are hallmarks of tumor cell growth. Tumor
      cell growth and morphology can be normalized by contact with nontransformed
      cells. The Src tyrosine kinase phosphorylates specific sites on the focal
      adhesion adaptor protein Crk-associated substrate (Cas) to promote nonanchored
      cell growth and migration. We studied the effects of Src and Cas on the
      expression of >14,000 genes to identify molecular events that underlie these
      activities. Gene expression in tumor cells that were normalized by neighboring
      nontransformed cells was used as an additional filter to identify genes that
      control metastatic cell growth. This process enabled the identification of genes
      that play roles in anchorage-independent cell growth and migration. One
      candidate, four and a half LIM domains 1 (Fhl1), acts as a transcriptional
      regulator that can associate with cell junctions as well as with the nucleus. We
      show here that Src phosphorylates Cas to block Fhl1 expression. In addition,
      suppression of Fhl1 is required for Src to promote tumor cell growth. These data
      show that Fhl1 is a tumor suppressor gene that acts downstream of Src and Cas to
      specifically block anchorage-independent cell growth and migration. Moreover,
      Fhl1 was suppressed in tumors from several human tissues. Thus, identification of
      how Fhl1 controls fundamental aspects of tumor cell growth and metastasis may
      lead to the development of novel markers that can be used to diagnose human
      clinical specimens as well as open innovative avenues of investigations aimed at
      developing reagents that target cancer cells while minimizing damage to normal
      cells.

PMID- 16452212
TI  - von Hippel-Lindau tumor suppressor protein regulates the assembly of
      intercellular junctions in renal cancer cells through hypoxia-inducible factor
      independent mechanisms.
AB  - Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene is responsible
      for the development of renal cell cancers (RCC), pheochromocytomas, and tumors in
      other organs. The best known function of VHL protein (VHL) is to target the
      hypoxia-inducible factor (HIF) for proteasome degradation. VHL is also required
      for the establishment of an epithelial-like cell shape in otherwise fibroblastic
      like RCC cell lines. However, the underlying mechanisms and whether this is
      linked to HIF remain undetermined. Because the breakage of intercellular
      junctions induces a fibroblastic-like phenotype in multiple cancer cell models,
      we hypothesized that VHL may be required for the assembly of intercellular
      junctions in RCC cells. Our experiments showed that VHL in RCC cell lines is
      necessary for the normal organization of adherens and tight intercellular
      junctions, the maintenance of cell polarity, and control of paracellular
      permeability. Additionally, 786-O cells reconstituted with wild-type VHL and with
      a constitutively active form of HIF-2alpha did not reproduce any of the
      phenotypic alterations of VHL-negative cells. In summary, we show that VHL
      inactivation in RCC cells disrupts intercellular junctions and cell shape through
      HIF-independent events, supporting the concept that VHL has additional functions
      beside its role in the regulation of HIF.

PMID- 16452213
TI  - Mutations in the PI3K/PTEN/TSC2 pathway contribute to mammalian target of
      rapamycin activity and increased translation under hypoxic conditions.
AB  - Decreased oxygen causes a rapid inhibition of mRNA translation. An important
      regulatory mechanism of translational repression under hypoxic conditions
      involves inhibition of the mammalian target of rapamycin (mTOR). mTOR is a target
      of the phosphatase and tensin homologue detected on chromosome 10
      (PTEN)/phosphatidylinositol 3-kinase/AKT/TSC2 pathway, a pathway that is
      frequently mutated in human cancers. Although hypoxia has been shown to inhibit
      mTOR activity, we show here that the hypoxia-induced inhibition of mTOR activity
      is attenuated in cells lacking TSC2 or PTEN, resulting in a higher translation
      rate even under hypoxic conditions. Comparison of mTOR inhibition by hypoxia
      alone or in combination with rapamycin showed that prolonged exposure to hypoxia
      was required to fully inhibit mTOR activity even in wild-type cells. Increased
      mTOR activity and protein synthesis did not translate into enhanced cell
      proliferation rates. However, lack of TSC2 resulted in a survival advantage when
      cells were exposed to hypoxia. Protection against hypoxia-induced cell death due
      to TSC2 deficiency is rapamycin-resistant, suggesting that TSC2 affects an
      apoptotic pathway. Tumors derived from TSC2 wild-type cells exhibited a growth
      delay compared with TSC2-deficient tumors, indicating that enhanced mTOR activity
      is advantageous in the initial phase of tumor growth. Therefore, failure to
      inhibit mTOR under oxygen-limiting conditions can be affected by upstream
      activating mutations and increases the survival and growth of hypoxic tumor
      cells.

PMID- 16452214
TI  - B7-h4 is a novel membrane-bound protein and a candidate serum and tissue
      biomarker for ovarian cancer.
AB  - Using cDNA database mining strategies and real-time quantitative reverse
      transcription-PCR, we identified B7-H4 as a novel gene that is overexpressed in
      ovarian and breast cancer tissues when compared with normal tissues. The gene
      encodes a protein of 282 amino acids with a signal sequence, an immunoglobulin
      domain, and a COOH-terminal hydrophobic transmembrane domain.
      Immunohistochemistry experiments show plasma membrane staining in serous ovarian
      and breast cancer, confirming the tissue specificity and cell surface
      localization. We have developed a sensitive dual monoclonal antibody sandwich
      ELISA to analyze the level of B7-H4 protein in >2,500 serum samples, ascites
      fluids, and tissue lysates. High levels of B7-H4 protein were detected in ovarian
      cancer tissue lysates when compared with normal tissues. B7-H4 was present at low
      levels in all sera but showed an elevated level in serum samples from ovarian
      cancer patients when compared with healthy controls or women with benign
      gynecologic diseases. The median B7-H4 concentration in endometrioid and serous
      histotypes was higher than in mucinous histotypes, consistent with results of
      immunohistochemical staining. The multivariate logistic regression analysis of B7
      H4 and CA125 measured in the same sample set resulted in an area under the curve
      (AUC) of 0.86 for all stages and 0.86 for stage I/II patients, which was
      significantly higher than the AUC for either marker alone. In early-stage
      patients, the sensitivity at 97% specificity increased from 52% for CA125 alone
      to 65% when used in combination with B7-H4. We conclude that B7-H4 is a promising
      new biomarker for ovarian carcinoma.

PMID- 16452215
TI  - Octreotide, a somatostatin analogue, mediates its antiproliferative action in
      pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and
      inducing Zac1 expression.
AB  - Somatostatin limits cell growth by inhibiting the proliferative activity of
      growth factor receptors. In this study, it is shown that in pituitary tumor
      cells, the somatostatin analogue octreotide produces its antiproliferative action
      by inducing the expression the tumor suppressor gene Zac1. ZAC/Zac1 induces cell
      cycle arrest and apoptosis and is highly expressed in normal pituitary, mammary,
      and ovarian glands but is down-regulated in pituitary, breast, and ovarian
      tumors. Knocking down Zac1 by RNA interference abolished the antiproliferative
      effect of octreotide in pituitary tumor cells, indicating that Zac1 is necessary
      for the action of octreotide. The effect of octreotide on Zac1 expression was
      pertussis toxin sensitive and was abolished after transfection with a dominant
      negative vector for SHP-1. Zac1 is a target of the phosphatidylinositol 3-kinase
      (PI3K) survival pathway. Octreotide treatment decreased the tyrosine
      phosphorylation levels of the PI3K regulatory subunit p85, induced
      dephosphorylation of phosphoinositide-dependent kinase 1 (PDK1) and Akt, and
      activated glycogen synthase kinase 3beta (GSKbeta). Therefore, in pituitary tumor
      cells, somatostatin analogues produce their antiproliferative action by acting on
      the PI3K/Akt signaling pathway and increasing Zac1 gene expression.

PMID- 16452216
TI  - EFA6A enhances glioma cell invasion through ADP ribosylation factor
      6/extracellular signal-regulated kinase signaling.
AB  - EFA6A, or Pleckstrin and Sec7 domain protein, is a member of guanine nucleotide
      exchange factors for ADP ribosylation factor 6 (ARF6). Whereas EFA6A is
      specifically expressed in the brain, little is known about its function in glial
      cells or glioma. Here we show that elevated EFA6A expression is detectable in
      both low-grade and high-grade human glioma tissues samples. To investigate the
      role of EFA6A in glioma carcinogenesis, we generated a human glioblastoma cell
      line which conditionally overexpresses EFA6A (U373-EFA6A). We showed that
      overexpression of EFA6A had no effect on cell proliferation, apoptosis, or cell
      cycle control. However, as shown by wound healing and in vitro cell invasion
      assays, it significantly enhanced the cell motility and invasiveness whereas
      silencing EFA6A by its dominant negative mutant EFA6A(E242K) produced opposite
      effects. We further showed that ARF6/extracellular signal-regulated kinase (ERK)
      signaling is required for the EFA6A-mediated cell invasion because both
      EFA6A(E242K) and ARF6 dominant negative mutant ARF6(T27N) markedly reduced the
      phosphorylated ERK level and EFA6A-mediated invasive capacity. Consistently,
      mitogen-activated protein kinase/ERK kinase inhibitor U0126 could abolish the
      EFA6A-induced cell invasion. These results suggest for the first time a potential
      role of EFA6A/ARF6/ERK signal cascade in glioma cell migration and invasion.

PMID- 16452217
TI  - Growth properties of colonic tumor cells are a function of the intrinsic
      mitochondrial membrane potential.
AB  - Development of malignant transformation in the colonic mucosa includes disruption
      in the equilibrium between proliferation and apoptosis, decreased expression and
      deletions of the mitochondrial genome, alterations in mitochondrial enzymatic
      activity, and elevations in the mitochondrial membrane potential (Deltapsim).
      Focusing on the role of the Deltapsim in tumor development and progression, we
      generated novel isogenic colonic carcinoma cell lines that exhibit highly
      significant, stable differences in their intrinsic Deltapsim. Using these cell
      lines, we have recently shown that the intrinsic Deltapsim has a significant
      influence on steady state mitochondrial activity and the extent to which cells
      enter butyrate-mediated growth arrest and apoptotic cascades. Here, we report
      that the Deltapsim is also profoundly linked to important tumorigenic properties
      of the cells. Compared with cells with lower Deltapsim, cells with elevated
      intrinsic Deltapsim have an enhanced capacity to (a) respond to hypoxia by
      avoiding apoptosis and initiating angiogenesis, (b) escape anoikis and grow under
      anchorage-independent conditions, and (c) invade the basement membrane. Combined
      with our previous work, these data implicate the intrinsic Deltapsim of colonic
      carcinoma cells in determining the probability of tumor expansion and
      progression.

PMID- 16452218
TI  - An integrated computational/experimental model of tumor invasion.
AB  - The intracellular and extracellular dynamics that govern tumor growth and
      invasiveness in vivo remain poorly understood. Cell genotype and phenotype, and
      nutrient, oxygen, and growth factor concentrations are key variables. In previous
      work, using a reaction-diffusion mathematical model based on variables that
      directly describe tumor cell cycle and biology, we formulated the hypothesis that
      tumor morphology is determined by the competition between heterogeneous cell
      proliferation caused by spatial diffusion gradients, e.g., of cell nutrients,
      driving shape instability and invasive tumor morphologies, and stabilizing
      mechanical forces, e.g., cell-to-cell and cell-to-matrix adhesion. To test this
      hypothesis, we here obtain variable-based statistics for input to the
      mathematical model from in vitro human and rat glioblastoma cultures. A linear
      stability analysis of the model predicts that glioma spheroid morphology is
      marginally stable. In agreement with this prediction, for a range of variable
      values, unbounded growth of the tumor mass and invasion of the environment are
      observed in vitro. The mechanism of invasion is recursive subspheroid component
      development at the tumor viable rim and separation from the parent spheroid.
      Results of computer simulations of the mathematical model closely resemble the
      morphologies and spatial arrangement of tumor cells from the in vitro model. We
      propose that tumor morphogenesis in vivo may be a function of marginally stable
      environmental conditions caused by spatial variations in cell nutrients, oxygen,
      and growth factors, and that controlling these conditions by decreasing spatial
      gradients could benefit treatment outcomes, whereas current treatment, and
      especially antiangiogenic therapy, may trigger spatial heterogeneity (e.g., local
      hypoxia), thus causing invasive instability.

PMID- 16452219
TI  - Inhibition of glutamate cysteine ligase activity sensitizes human breast cancer
      cells to the toxicity of 2-deoxy-D-glucose.
AB  - It has been hypothesized that cancer cells increase glucose metabolism to protect
      against metabolic fluxes of hydroperoxides via glutathione-dependent peroxidases.
      2-Deoxy-D-glucose, inhibits glucose metabolism and has been shown to cause
      cytotoxicity in cancer cells that is partially mediated by disruptions in thiol
      metabolism. In the current study, human breast cancer cells were continuously
      treated (24 hours) with 2-deoxy-D-glucose, and total glutathione content as well
      as the expression of the first enzyme in the glutathione synthetic pathway
      [glutamate cysteine ligase (GCL)] were found to be induced 2.0-fold. Inhibiting
      GCL activity during 2-deoxy-D-glucose exposure using l-buthionine-[S,R]
      sulfoximine (BSO) significantly enhanced the cytotoxic effects of 2-deoxy-D
      glucose and caused increases in endpoints indicative of oxidative stress,
      including % oxidized glutathione and steady-state levels of pro-oxidants as
      assayed using an oxidation-sensitive fluorescent probe. These results show that
      treatment of human breast cancer cells with 2-deoxy-d-glucose causes metabolic
      oxidative stress that is accompanied by increases in steady-state levels of GCL
      mRNA, GCL activity, and glutathione content. Furthermore, inhibition of 2-deoxy-D
      glucose-mediated induction of GCL activity with BSO increases endpoints
      indicative of oxidative stress and sensitizes cancer cells to 2-deoxy-D-glucose
      induced cytotoxicity. These results support the hypothesis that drug combinations
      capable of inhibiting both glucose and hydroperoxide metabolism may provide an
      effective biochemical strategy for sensitizing human cancer cells to metabolic
      oxidative stress.

PMID- 16452220
TI  - The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis
      in melanoma cells.
AB  - Mitogen-activated protein kinase (MAPK) is activated in the majority of
      melanomas, and its activity is essential for cell survival. In this report, we
      examined the effects of a novel raf inhibitor BAY 43-9006 on melanoma cell
      viability and intracellular signaling and found that it induces apoptosis through
      a caspase-independent mechanism. At concentrations that suppress extracellular
      signal-regulated kinase (ERK) phosphorylation, BAY 43-9006 dephosphorylates Bad
      on Ser(75) and Ser(99), activates Bak and Bax, and reduces the mitochondrial
      transmembrane potential. BAY 43-9006 (sorafenib) down-modulates the levels of Bcl
      2 and Bcl-X(L) in a MAPK-independent manner in A2058 and SKMEL5 melanoma cells
      but not in the more resistant A375 cells. Of the three lines tested, only A375
      cells were rescued from BAY 43-9006-induced apoptosis by knocking down Bad. BAY
      43-9006 induced poly(ADP-ribose) polymerase cleavage and the mitochondrial
      release of cytochrome c and SMAC. However, the pan-caspase inhibitor Z-VAD-fmk
      had only a modest protective effect against the drug, suggesting that BAY 43-9006
      induced apoptosis is largely caspase independent. BAY 43-9006 but not the MAP/ERK
      kinase inhibitors PD98059 or U0126 induced the nuclear translocation of apoptosis
      inducing factor (AIF) in A2058 and SKMEL5 cells, and the introduction of a small
      interfering RNA (siRNA) for AIF partially protected these cells from BAY 43-9006
      induced apoptosis. The AIF siRNA had little effect in A375 cells, in which drug
      induced AIF release was negligible. These data indicate that in sensitive cell
      lines, BAY 43-9006-induced apoptosis is independent of Bad dephosphorylation and
      caspase activation and largely mediated through the nuclear translocation of AIF.

PMID- 16452221
TI  - Increased efficacy and safety in the treatment of experimental liver cancer with
      a novel adenovirus-alphavirus hybrid vector.
AB  - An improved viral vector for cancer gene therapy should be capable of infecting
      tumors with high efficiency, inducing specific and high-level expression of
      transgene in the tumor and selectively destroying tumor cells. In the design of
      such a vector to treat hepatocellular carcinoma, we took advantage of (a) the
      high infectivity of adenoviruses for hepatic cells, (b) the high level of protein
      expression and proapoptotic properties that characterize Semliki Forest virus
      (SFV) replicon, and (c) tumor selectivity provided by alpha-fetoprotein (AFP)
      promoter. We constructed a hybrid viral vector composed of a helper-dependent
      adenovirus containing an SFV replicon under the transcriptional control of AFP
      promoter and a transgene driven by SFV subgenomic promoter. Hybrid vectors
      containing murine interleukin-12 (mIL-12) genes or reporter gene LacZ showed very
      specific and high-level expression of transgenes in AFP-expressing hepatocellular
      carcinoma cells, both in vitro and in an in vivo hepatocellular carcinoma animal
      model. Infected hepatocellular carcinoma cells were selectively eliminated due to
      the induction of apoptosis by SFV replication. In a rat orthotopic liver tumor
      model, treatment of established tumors with a hybrid vector carrying mIL-12 gene
      resulted in strong antitumoral activity without accompanying toxicity. This new
      type of hybrid vectors may provide a potent and safe tool for cancer gene
      therapy.

PMID- 16452222
TI  - Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2
      overexpressing and trastuzumab-treated breast cancer cells.
AB  - Lapatinib (GW572016) is a selective inhibitor of both epidermal growth factor
      receptor (EGFR) and HER-2 tyrosine kinases. Here, we explore the therapeutic
      potential of lapatinib by testing its effect on tumor cell growth in a panel of
      31 characterized human breast cancer cell lines, including trastuzumab
      conditioned HER-2-positive cell lines. We further characterize its activity in
      combination with trastuzumab and analyze whether EGFR and HER-2 expression or
      changes induced in the activation of EGFR, HER-2, Raf, AKT, or extracellular
      signal-regulated kinase (ERK) are markers of drug activity. We report that
      concentration-dependent antiproliferative effects of lapatinib were seen in all
      breast cancer cell lines tested but varied significantly between individual cell
      lines with up to 1,000-fold difference in the IC(50)s (range, 0.010-18.6
      micromol/L). Response to lapatinib was significantly correlated with HER-2
      expression and its ability to inhibit HER-2, Raf, AKT, and ERK phosphorylation.
      Long-term in vivo lapatinib studies were conducted with human breast cancer
      xenografts in athymic mice. Treatment over 77 days resulted in a sustained and
      significant reduction in xenograft volume compared with untreated controls. For
      the combination of lapatinib plus trastuzumab, synergistic drug interactions were
      observed in four different HER-2-overexpressing cell lines. Moreover, lapatinib
      retained significant in vitro activity against cell lines selected for long-term
      outgrowth (>9 months) in trastuzumab-containing (100 microg/mL) culture medium.
      These observations provide a clear biological rationale to test lapatinib as a
      single agent or in combination with trastuzumab in HER-2-overexpressing breast
      cancer and in patients with clinical resistance to trastuzumab.

PMID- 16452223
TI  - Regulation of survivin by ErbB2 signaling: therapeutic implications for ErbB2
      overexpressing breast cancers.
AB  - In breast cancer, overexpression of ErbB2 or aberrant regulation of survivin, a
      member of the inhibitor of apoptosis family, is associated with resistance to
      chemo/hormone therapy and predicts for a poor clinical outcome. A functional link
      between the two predictive factors has not been previously shown. Here, using
      genetic and pharmacologic approaches to block ErbB2 signaling, we show that ErbB2
      regulates survivin protein expression in ErbB2-overexpressing breast cancer
      cells. Selective knockdown of ErbB2 using small interfering RNA markedly reduced
      survivin protein, resulting in apoptosis of ErbB2-overexpressing breast cancer
      cell lines such as BT474. Alternatively, inhibition of ErbB2 signaling using
      lapatinib (GW572016), a reversible small-molecule inhibitor of ErbB1/ErbB2
      tyrosine kinases, at pharmacologically relevant concentrations, leads to marked
      inhibition of survivin protein with subsequent apoptosis. The effect of lapatinib
      on survivin seems to be predominantly posttranslational, mediated by ubiquitin
      proteosome degradation as lactacystin, a proteosome inhibitor, reverses these
      effects. Furthermore, lapatinib down-regulated the expression of His-tagged
      survivin, which was under the transcriptional control of a heterologous promoter,
      providing additional evidence supporting a posttranslational mechanism of
      regulation. In contrast, trastuzumab and gefitinib failed to down-regulate
      survivin in ErbB2-overexpressing breast cancer cells. Importantly, the clinical
      relevance of these findings was illustrated in patients with ErbB2-overexpressing
      breast cancer whose clinical response to lapatinib was associated with marked
      inhibition of survivin in their tumors. These findings shed new light on the
      mechanism by which ErbB2 overexpression protects against apoptotic stimuli in
      breast cancer and identifies therapeutic interventions to improve clinical
      outcomes in these aggressive tumors.

PMID- 16452224
TI  - Transforming growth factor-beta receptor inhibition enhances adenoviral
      infectability of carcinoma cells via up-regulation of Coxsackie and Adenovirus
      Receptor in conjunction with reversal of epithelial-mesenchymal transition.
AB  - Expression of the Coxsackie and Adenovirus Receptor (CAR) is frequently reduced
      in carcinomas, resulting in decreased susceptibility of such tumors to infection
      with therapeutic adenoviruses. Because CAR participates physiologically in the
      formation of tight-junction protein complexes, we examined whether molecular
      mechanisms known to down-regulate cell-cell adhesions cause loss of CAR
      expression. Transforming growth factor-beta (TGF-beta)-mediated epithelial
      mesenchymal transition (EMT) is a phenomenon associated with tumor progression
      that is characterized by loss of epithelial-type cell-cell adhesion molecules
      (including E-cadherin and the tight junction protein ZO-1), gain of mesenchymal
      biochemical markers, such as fibronectin, and acquisition of a spindle cell
      phenotype. CAR expression is reduced in tumor cells that have undergone EMT in
      response to TGF-beta. This down-regulation results from repression of CAR gene
      transcription, whereas altered RNA stability and increased proteasomal protein
      degradation play no role. Loss of CAR expression in response to TGF-beta is
      accompanied by reduced susceptibility to adenovirus infection. Indeed, treatment
      of carcinoma cells with LY2109761, a specific pharmacologic inhibitor of TGF-beta
      receptor types I and II kinases, resulted in increased CAR RNA and protein levels
      as well as improved infectability with adenovirus. This was observed in cells
      induced to undergo EMT by addition of exogenous TGF-beta and in those that were
      transformed by endogenous autocrine/paracrine TGF-beta. These findings show down
      regulation of CAR in the context of EMT and suggest that combination of
      therapeutic adenoviruses and TGF-beta receptor inhibitors could be an efficient
      anticancer strategy.

PMID- 16452225
TI  - Identification of a melanoma marker derived from melanoma-associated endogenous
      retroviruses.
AB  - We previously described the expression of melanoma-associated endogenous
      retrovirus (MERV) proteins and viral particles in human melanomas and metastases.
      The objective of the present study was to determine whether a humoral immune
      response to MERV proteins occurs in melanoma. Candidate B-cell epitopes on MERV
      proteins were predicted using bioinformatic screening. The reactivity of MERV
      peptides corresponding to the predicted epitopes with antibodies prevalent in
      sera of melanoma patients was analyzed. An immunodominant peptide located in the
      env protein of MERV was identified. Subsequent analyzes using 81 samples from
      stage I to stage IV melanoma patients and 95 sera from healthy subjects revealed
      statistically significant differences in seroprevalence of antibodies in melanoma
      sera samples when compared with reference samples from healthy subjects. The
      prevalence of anti-MERV antibodies in melanoma patient sera was confirmed by
      immunofluorescence on env-transfected cells. These data indicate the potential of
      this candidate peptide as target for diagnosis and immunotherapy.

PMID- 16452226
TI  - Low-dose metronomic daily cyclophosphamide and weekly tirapazamine: a well
      tolerated combination regimen with enhanced efficacy that exploits tumor hypoxia.
AB  - The recent clinical successes of antiangiogenic drug-based therapies have also
      served to highlight the problem of acquired resistance because, similar to other
      types of cancer therapy, tumors that initially respond eventually stop doing so.
      Consequently, strategies designed to delay resistance or treat resistant
      subpopulations when they arise have assumed considerable importance. This
      requires a better understanding of the various possible mechanisms for
      resistance. In this regard, reduced oxygenation is thought to be a key mediator
      of the antitumor effects of antiangiogenic therapies; accordingly, increased
      hypoxia tolerance of the tumor cells presents a potential mechanism of
      resistance. However, hypoxia can also be exploited therapeutically through the
      use of hypoxic cell cytotoxins, such as tirapazamine. With this in mind, we
      measured the oxygenation of PC-3 human prostate cancer xenografts subjected to
      chronic low-dose metronomic (LDM) antiangiogenic chemotherapy using
      cyclophosphamide given through the drinking water. We found that LDM
      cyclophosphamide impairs the oxygenation of PC-3 xenografts even during relapse,
      coinciding with reduced microvessel density. Combination of LDM cyclophosphamide
      with tirapazamine results in significantly improved tumor control in the PC-3, HT
      29 colon adenocarcinoma, and MDA-MB-231 breast cancer human xenograft models
      without having a negative effect on the favorable toxicity profile of LDM
      cyclophosphamide. These results provide further evidence that reduced vascular
      dependence/increased hypoxia tolerance may be a basis for eventual resistance of
      tumors exposed to long-term LDM chemotherapy.

PMID- 16452227
TI  - The dispersal of replication proteins after Etoposide treatment requires the
      cooperation of Nbs1 with the ataxia telangiectasia Rad3-related/Chk1 pathway.
AB  - In mammalian cells, DNA replication takes place in functional subnuclear
      compartments, called replication factories, where replicative factors accumulate.
      The distribution pattern of replication factories is diagnostic of the different
      moments (early, mid, and late) of the S phase. This dynamic organization is
      affected by different agents that induce cell cycle checkpoint activation via DNA
      damage or stalling of replication forks. Here, we explore the cell response to
      etoposide, an anticancer drug belonging to the topoisomerase II poisons.
      Etoposide does not induce an immediate block of DNA synthesis and progressively
      affects the distribution of replication proteins in S phase. First, it triggers
      the formation of large nuclear foci that contain the single-strand DNA binding
      protein replication protein A (RPA), suggesting that lesions produced by the drug
      are processed into extended single-stranded regions. These RPA foci colocalize
      with DNA replicated at the beginning of the treatment. Etoposide also triggers
      the dispersal of replicative proteins, proliferating cell nuclear antigen and DNA
      ligase I, from replication factories. This event requires the activity of the
      ataxia telangiectasia Rad3-related (ATR) checkpoint kinase. By comparing the
      effect of the drug in cell lines defective in different DNA repair and checkpoint
      pathways, we show that, along with the downstream kinase Chk1, the Nbs1 protein,
      mutated in the Nijmegen breakage syndrome, is also relevant for this response and
      for ATR-dependent phosphorylation. Finally, our analysis evidences a critical
      role of Nbs1 in the etoposide-induced inhibition of DNA replication in early S
      phase.

PMID- 16452228
TI  - Hypoxia-inducible factor-1alpha promotes nonhypoxia-mediated proliferation in
      colon cancer cells and xenografts.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that
      directly transactivates genes important for the growth and metabolism of solid
      tumors. HIF-1alpha is overexpressed in cancer, and its level of expression is
      correlated with patient mortality. Increased synthesis or stability of HIF-1alpha
      can be induced by hypoxia-dependent or hypoxia-independent factors. Thus, HIF
      1alpha is expressed in both nonhypoxic and hypoxic cancer cells. The role of HIF
      1alpha in nonhypoxia-mediated cancer cell proliferation remains speculative. We
      have disrupted HIF-1alpha by targeted homologous recombination in HCT116 and RKO
      human colon cancer cells. Loss of HIF-1alpha significantly reduced nonhypoxia
      mediated cell proliferation in vitro and in vivo. Paradoxically, loss of HIF
      1alpha expression did not grossly affect the hypoxic compartments within tumor
      xenografts in vivo, although HIF-1alpha promoted cell proliferation and survival
      under hypoxia in vitro. To further test the role of HIF-1alpha within tumor
      compartments, we generated cells with combined disruptions of both HIF-1alpha and
      vascular endothelial growth factor (VEGF). In all xenografts, disruption of VEGF
      led to marked expansion of the hypoxic compartments and growth delay.
      Nonetheless, the presence or absence of HIF-1alpha did not grossly affect these
      expanded hypoxic compartments. These data provide compelling evidence that, in a
      subset of colon cancers, (a) HIF-1alpha is a positive factor for nonhypoxia
      mediated cell proliferation in vitro and in vivo and (b) HIF-1alpha is a positive
      factor for cell proliferation and survival under hypoxic conditions in vitro, but
      does not grossly contribute to the tumor hypoxic compartments in vivo.

PMID- 16452229
TI  - P21-activated kinase 1 regulation of estrogen receptor-alpha activation involves
      serine 305 activation linked with serine 118 phosphorylation.
AB  - Here, we investigated the role of P21-activated kinase 1 (Pak1) signaling in the
      function of estrogen receptor-alpha (ER-alpha) as assessed by serine 305 (S305)
      activation and transactivation activity of ER. We found that Pak1 overexpression
      interfered with the antiestrogenic action of tamoxifen upon the ER
      transactivation function in hormone-sensitive cells. In addition, tamoxifen
      stimulation led to up-regulation of ER target genes in breast cancer cells with
      increased Pak1 expression. Tamoxifen also increased Pak1-ER interaction in
      tamoxifen-resistant but not in tamoxifen-sensitive cells. Results from the
      mutational studies discovered a role of ER-S305 phosphorylation in triggering a
      subsequent phosphorylation of serine 118 (S118), and these effects were further
      potentiated by tamoxifen treatment. We found that S305 activation-linked ER
      transactivation function requires a functional S118, and active Pak1 signaling is
      required for a sustaining S118 phosphorylation of the endogenous ER. All of these
      events were positively influenced by tamoxifen and thus may contribute toward the
      loss of antiestrogenic effect of tamoxifen. These findings suggest that Pak1
      signaling-dependent activation of ER-S305 leads to an enhanced S118
      phosphorylation presumably due to a conformational change, and such structural
      modifications may participate in the development of tamoxifen resistance.

PMID- 16452230
TI  - Functional coupling of p38-induced up-regulation of BiP and activation of RNA
      dependent protein kinase-like endoplasmic reticulum kinase to drug resistance of
      dormant carcinoma cells.
AB  - It has been proposed that occult, disseminated metastatic cells are refractory to
      chemotherapy due to lack of proliferation. We have shown that p38 activation
      induces dormancy of squamous carcinoma cells. We now show that p38 signaling in
      these cells activates a prosurvival mechanism via the up-regulation of the
      endoplasmic reticulum (ER) chaperone BiP and increased activation of the ER
      stress-activated eukaryotic translation initiator factor 2alpha kinase RNA
      dependent protein kinase-like ER kinase (PERK) allowing dormant tumor cells to
      resist drug toxicity. RNA interference and dominant-negative expression studies
      revealed that both BiP and PERK signaling promote survival and drug resistance of
      dormant cells, and that BiP up-regulation prevents Bax activation. We propose
      that stress-dependent activation of p38 via BiP up-regulation and PERK activation
      protects dormant tumor cells from stress insults, such as chemotherapy.

PMID- 16452231
TI  - Increased levels of the FoxM1 transcription factor accelerate development and
      progression of prostate carcinomas in both TRAMP and LADY transgenic mice.
AB  - The proliferation-specific Forkhead Box M1 (FoxM1 or FoxM1b) transcription factor
      is overexpressed in a number of aggressive human carcinomas. Mouse hepatocytes
      deficient in FoxM1 fail to proliferate and are highly resistant to developing
      carcinogen-induced liver tumors. We previously developed a transgenic (TG) mouse
      line in which the ubiquitous Rosa26 promoter was used to drive expression of the
      human FoxM1b cDNA transgene in all mouse cell types. To investigate the role of
      FoxM1b in prostate cancer progression, we bred Rosa26-FoxM1b mice with both TRAMP
      and LADY TG mouse models of prostate cancer. We show that increased expression of
      FoxM1b accelerated development, proliferation, and growth of prostatic tumors in
      both TRAMP and LADY double TG mice. Furthermore, development of prostate
      carcinomas in TRAMP/Rosa26-FoxM1b double TG mice required high levels of FoxM1
      protein to overcome sustained expression of the alternative reading frame tumor
      suppressor, a potent inhibitor of FoxM1 transcriptional activity. Depletion of
      FoxM1 levels in prostate cancer cell lines PC-3, LNCaP, or DU-145 by small
      interfering RNA transfection caused significant reduction in proliferation and
      anchorage-independent growth on soft agar. This phenotype was associated with
      increased nuclear levels of the cyclin-dependent kinase inhibitor protein
      p27(Kip1) and diminished expression of S-phase promoting cyclin A2 and M-phase
      promoting cyclin B1 proteins. Finally, we show that elevated levels of FoxM1
      protein correlate with high proliferation rates in human prostate
      adenocarcinomas. Our results suggest that the FoxM1 transcription factor
      regulates development and proliferation of prostate tumors, and that FoxM1 is a
      novel target for prostate cancer treatment.

PMID- 16452232
TI  - Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic
      potential against hepatocyte growth factor/c-Met-dependent human tumors.
AB  - c-Met is a well-characterized receptor tyrosine kinase for hepatocyte growth
      factor (HGF). Compelling evidence from studies in human tumors and both cellular
      and animal tumor models indicates that signaling through the HGF/c-Met pathway
      mediates a plethora of normal cellular activities, including proliferation,
      survival, migration, and invasion, that are at the root of cancer cell
      dysregulation, tumorigenesis, and tumor metastasis. Inhibiting HGF-mediated
      signaling may provide a novel therapeutic approach for treating patients with a
      broad spectrum of human tumors. Toward this goal, we generated and characterized
      five different fully human monoclonal antibodies that bound to and neutralized
      human HGF. Antibodies with subnanomolar affinities for HGF blocked binding of
      human HGF to c-Met and inhibited HGF-mediated c-Met phosphorylation, cell
      proliferation, survival, and invasion. Using a series of human-mouse chimeric HGF
      proteins, we showed that the neutralizing antibodies bind to a unique epitope in
      the beta-chain of human HGF. Importantly, these antibodies inhibited HGF
      dependent autocrine-driven tumor growth and caused significant regression of
      established U-87 MG tumor xenografts. Treatment with anti-HGF antibody rapidly
      inhibited tumor cell proliferation and significantly increased the proportion of
      apoptotic U-87 MG tumor cells in vivo. These results suggest that an antibody to
      an epitope in the beta-chain of HGF has potential as a novel therapeutic agent
      for treating patients with HGF-dependent tumors.

PMID- 16452233
TI  - Resistance of cancers to immunologic cytotoxicity and adoptive immunotherapy via
      X-linked inhibitor of apoptosis protein expression and coexisting defects in
      mitochondrial death signaling.
AB  - The ability of cancers to evade immune surveillance and resist immunotherapy
      raises a fundamental question of how tumor cells survive in the presence of a
      competent immune system. Studies to address this question have primarily focused
      on mechanisms by which tumor cells avoid recognition by or induce tolerance in
      the immune system. However, little is known about whether cancer cells also
      acquire an intrinsic ability to resist killing by immune effectors. We find that
      cancer cells enhance their ability to withstand an attack by cytotoxic immune
      effector cells via acquisition of specific genetic alterations that interfere
      with the shared mitochondrial death signaling pathway entrained by granzyme B,
      IFN-gamma, and Apo2 ligand/tumor necrosis factor-related apoptosis inducing
      ligand (Apo2L/TRAIL), three key mediators of immunologic cell-mediated
      cytotoxicity. We show that the coexistence of specific mitochondrial signaling
      defects (either deletion of Bax, overexpression of Bcl-x(L), or deletion of Smac)
      with expression of X-linked inhibitor of apoptosis protein decreases the
      sensitivity of cancer cells to IFN-gamma/Apo2L/TRAIL- or granzyme B-induced
      apoptosis, lymphocyte-mediated cytotoxicity in vitro, and adoptive cellular
      immunotherapy in vivo. Conversely, negating X-linked inhibitor of apoptosis
      protein expression or function in tumor cells with defective mitochondrial
      signaling enables direct activation of caspase-3/-7 by granzyme B or Apo2L/TRAIL,
      and restores their susceptibility to immunologic cytotoxicity. These findings
      identify an important mechanism by which cancers evade elimination by immune
      effector cells and suggest that cancer immunotherapy might be improved by
      concurrent strategies to alleviate or circumvent the intrinsic mitochondrial
      death signaling defects that help cancer cells resist immunologic cytotoxicity.

PMID- 16452235
TI  - Identification of arctigenin as an antitumor agent having the ability to
      eliminate the tolerance of cancer cells to nutrient starvation.
AB  - Tumor cells generally proliferate rapidly and the demand for essential nutrients
      as well as oxygen always exceeds the supply due to the unregulated growth and the
      insufficient and inappropriate vascular supply. However, cancer cells show an
      inherent ability to tolerate extreme conditions, such as that characterized by
      low nutrient and oxygen supply, by modulating their energy metabolism. Thus,
      targeting nutrient-deprived cancer cells may be a novel strategy in anticancer
      drug development. Based on that, we established a novel screening method to
      discover anticancer agents that preferentially inhibit cancer cell viability
      under the nutrient-deprived condition. After screening 500 medicinal plant
      extracts used in Japanese Kampo medicine, we found that a CH(2)Cl(2)-soluble
      extract of Arctium lappa exhibited 100% preferential cytotoxicity under the
      nutrient-deprived condition at a concentration of 50 microg/mL with virtually no
      cytotoxicity under nutrient-rich condition. Further bioassay-guided fractionation
      and isolation led to the isolation of arctigenin as the primary compound
      responsible for such preferential cytotoxicity; the compound exhibited 100%
      preferential cytotoxicity against nutrient-deprived cells at a concentration of
      0.01 microg/mL. Furthermore, arctigenin was also found to strongly suppress the
      PANC-1 tumor growth in nude mice, as well as the growth of several of the tested
      pancreatic cancer cell lines, suggesting the feasibility of this novel
      antiausterity approach in cancer therapy. Further investigation of the mechanism
      of action of arctigenin revealed that the compound blocked the activation of Akt
      induced by glucose starvation, which is a key process in the tolerance exhibited
      by cancer cells to glucose starvation.

PMID- 16452234
TI  - Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-resistant hepatoma cells to TRAIL-induced apoptosis through reactive
      oxygen species-mediated up-regulation of DR5.
AB  - Sulforaphane is a chemopreventive agent present in various cruciferous
      vegetables, including broccoli. Here, we show that treatment with tumor necrosis
      factor (TNF)-related apoptosis-inducing ligand (TRAIL) in combination with
      subtoxic doses of sulforaphane significantly induces rapid apoptosis in TRAIL
      resistant hepatoma cells. Neither TNF-alpha- nor Fas-mediated apoptosis was
      sensitized in hepatoma cells by cotreatment with sulforaphane, suggesting that
      sulforaphane can selectively sensitize cells to TRAIL-induced apoptosis but not
      to apoptosis mediated by other death receptors. We found that sulforaphane
      treatment significantly up-regulated mRNA and protein levels of DR5, a death
      receptor of TRAIL. This was accompanied by an increase in the generation of
      reactive oxygen species (ROS). Pretreatment with N-acetyl-l-cysteine and
      overexpression of catalase inhibited sulforaphane-induced up-regulation of DR5
      and almost completely blocked the cotreatment-induced apoptosis. Furthermore, the
      sulforaphane-mediated sensitization to TRAIL was efficiently reduced by
      administration of a blocking antibody or small interfering RNAs for DR5. These
      results collectively indicate that sulforaphane-induced generation of ROS and the
      subsequent up-regulation of DR5 are critical for triggering and amplifying TRAIL
      induced apoptotic signaling. We also found that sulforaphane can sensitize both
      Bcl-xL- and Bcl-2-overexpressing hepatoma cells to TRAIL-induced apoptosis,
      indicating that treatment with a combination of TRAIL and sulforaphane may be a
      safe strategy for treating resistant hepatomas.

PMID- 16452236
TI  - The cyclin-dependent kinase 2 inhibitor down-regulates interleukin-1beta-mediated
      induction of cyclooxygenase-2 expression in human lung carcinoma cells.
AB  - Overexpression of cyclooxygenase-2 (COX-2) is frequently observed in several
      human cancers, including lung, colon, and head and neck. Malignancies are also
      associated with the dysregulation of cell cycle events and concomitant elevated
      activity of cyclin-dependent kinases (CDK). CDK2 is a key cell cycle regulatory
      protein that controls the transition of cells from G(1) to S phase. In this
      study, we furnish several lines of evidence that show a functional role for the
      CDK2 in interleukin-1beta (IL-1beta)-induced COX-2 expression in H358 human non
      small cell lung carcinoma cell line by blocking CDK2 activity. First, we show
      that BMS-387032, a potent CDK2 inhibitor, blocks IL-1beta-induced expression as
      well as steady-state mRNA levels of COX-2. Second, we show that small interfering
      RNA that abrogates CDK2 expression also blocks IL-1beta-induced COX-2 expression.
      Third, results from in vitro kinase assays clearly show that IL-1beta induces
      CDK2 activity in H358 cells and this activity is significantly inhibited by BMS
      387032. Moreover, CDK2 inhibition blocks IL-1beta-induced binding to the NF-IL6
      element of the COX-2 promoter and inhibits transcription of the COX-2 gene. We
      also observed that BMS-387032 does not inhibit endogenous expression of COX-2 or
      prostaglandin synthesis in lung carcinoma cells. Finally, we provide evidence
      showing that IL-1beta-induced signaling events, such as p38 mitogen-activated
      protein kinase, phosphorylated stress-activated protein kinase/c-Jun NH(2)
      terminal kinase, phosphorylated AKT, and phosphorylated extracellular signal
      regulated kinase 1/2, are not inhibited by CDK2 inhibitor. Taken together, the
      data suggest that CDK2 activity may play an important event in the IL-1beta
      induced COX-2 expression and prostaglandin E(2) synthesis and might represent a
      novel target for BMS-387032.

PMID- 16452237
TI  - A novel small-molecule inhibitor of protein kinase Ciota blocks transformed
      growth of non-small-cell lung cancer cells.
AB  - We recently showed that atypical protein kinase Ciota (PKCiota) is required for
      transformed growth of human non-small-cell lung cancer (NSCLC) cells by
      activating Rac1. Genetic disruption of PKCiota signaling blocks Rac1 activity and
      transformed growth, indicating that PKCiota is a viable target for development of
      novel therapeutics for NSCLC. Here, we designed and implemented a novel
      fluorescence resonance energy transfer-based assay to identify inhibitors of
      oncogenic PKCiota signaling. This assay was used to identify compounds that
      disrupt the interaction between PKCiota and its downstream effector Par6, which
      links PKCiota to Rac1. We identified aurothioglucose (ATG), a gold compound used
      clinically to treat rheumatoid arthritis, and the related compound,
      aurothiomalate (ATM), as potent inhibitors of PKCiota-Par6 interactions in vitro
      (IC(50) approximately 1 micromol/L). ATG blocks PKCiota-dependent signaling to
      Rac1 and inhibits transformed growth of NSCLC cells. ATG-mediated inhibition of
      transformation is relieved by expression of constitutively active Rac1,
      consistent with a mechanism at the level of the interaction between PKCiota and
      Par6. ATG inhibits A549 cell tumor growth in nude mice, showing efficacy against
      NSCLC in a relevant preclinical model. Our data show the utility of targeting
      protein-protein interactions involving PKCiota for antitumor drug development and
      provide proof of concept that chemical disruption of PKCiota signaling can be an
      effective treatment for NSCLC. ATG and ATM will be useful reagents for studying
      PKCiota function in transformation and represent promising new agents for the
      clinical treatment of NSCLC.

PMID- 16452238
TI  - The immunomodulatory benzodiazepine Bz-423 inhibits B-cell proliferation by
      targeting c-myc protein for rapid and specific degradation.
AB  - Myc proteins regulate cell growth and are oncogenic in many cancers. Although
      these proteins are validated molecular anticancer targets, new therapies aimed at
      modulating myc have yet to emerge. A benzodiazepine (Bz-423) that was discovered
      in efforts to find new drugs for lupus was found recently to have
      antiproliferative effects on Burkitt's lymphoma cells. We now show that the basis
      for the antiproliferative effects of Bz-423 is the rapid and specific depletion
      of c-myc protein, which is coupled to growth-suppressing effects on key
      regulators of proliferation and cell cycle progression. c-Myc is depleted as a
      result of signals coupled to Bz-423 binding its molecular target, the oligomycin
      sensitivity-conferring protein subunit of the mitochondrial F(1)F(o)-ATPase. Bz
      423 inhibits F(1)F(o)-ATPase activity, blocking respiratory chain function and
      generating superoxide, which at growth-inhibiting concentrations triggers
      proteasomal degradation of c-myc. Bz-423-induced c-myc degradation is independent
      of glycogen synthase kinase but is substantially blocked by mutation of the
      phosphosensitive residue threonine 58, which when phosphorylated targets c-myc
      for ubiquitination and subsequent proteasomal degradation. Collectively, this
      work describes a new lead compound, with drug-like properties, which regulates c
      myc by a novel molecular mechanism that may be therapeutically useful.

PMID- 16452239
TI  - Targeting heat shock response to sensitize cancer cells to proteasome and Hsp90
      inhibitors.
AB  - Novel classes of anticancer drugs, including proteasome inhibitors and Hsp90
      inhibitors, potently induce heat shock proteins (Hsps). Because Hsps show
      antiapoptotic activities, we suggested that suppression of such induction may
      sensitize cancer cells to these drugs. Here, we knocked out the major heat shock
      transcription factor HSF-1 in several cancer cell lines using small interfering
      RNA and showed that such cells, which can no longer induce Hsps in response to
      proteasome and Hsp90 inhibitors, become more sensitive to these drugs.
      Furthermore, we developed a high-throughput screen for small molecules that
      inhibit induction of Hsps. The first step was a cell-based screen for inhibitors
      of Hsps-mediated luciferase refolding followed by a counterscreen for toxicity.
      The second step was a direct testing for inhibition of Hsp induction by
      immunoblotting with anti-Hsp72 antibody. After screening of 20,000 compounds from
      several diversity libraries, we focused on a compound we called NZ28, which
      potently inhibited induction of Hsps by heat shock, proteasome, and Hsp90
      inhibitors in a variety of cell lines, and showed no significant toxicity. After
      testing of a set of analogues of NZ28, we identified a structural element that
      was critical for the activity. We also identified another inhibitor of the Hsp
      induction that was practically nontoxic. This compound, which we called emunin,
      strongly sensitized myeloma cells to proteasome and Hsp90 inhibitors and prostate
      carcinoma cells to proteasome inhibitors. This work indicates that targeting the
      heat shock response may facilitate use of proteasome and Hsp90 inhibitors for
      cancer treatment.

PMID- 16452240
TI  - Application of Bayesian modeling of autologous antibody responses against ovarian
      tumor-associated antigens to cancer detection.
AB  - Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently
      needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We
      tested multiplex detection of antibodies to candidate ovarian TAAs and
      statistical modeling for discrimination of sera of EOC patients and controls.
      Binding of serum antibody of women with EOC or healthy controls to candidate TAA
      coated microspheres was assayed in parallel. A Bayesian model/variable selection
      approach using Markov Chain Monte Carlo computations was applied to these data,
      and serum CA125 values, to determine the best predictive model. The selected
      model was subjected to area under the receiver-operator curve (AUC) analysis. The
      best model generated an AUC of 0.86 [95% confidence interval (95% CI), 0.78-0.90]
      for discrimination between sera of EOC patients and healthy patients using
      antibody specific to p53, NY-CO-8, and HOXB7. Inclusion of CA125 in the model
      provided an AUC of 0.89 (95% CI, 0.84-0.92) compared with an AUC of 0.83 (95% CI,
      0.81-0.85) using CA125 alone. However, using TAA responses alone, the model
      discriminated between independent sera of women with nonmalignant gynecologic
      conditions and those with advanced-stage or early-stage EOC with AUCs of 0.71
      (95% CI, 0.67-0.76) and 0.70 (95% CI, 0.48-0.75), respectively. Serum antibody to
      p53 and HOXB7 is positively associated with EOC, whereas NY-CO-8-specific
      antibody shows negative association. Bayesian modeling of these TAA-specific
      serum antibody responses exhibits similar discrimination of patients with early
      stage and advanced-stage EOC from women with nonmalignant gynecologic conditions
      and may be complementary to CA125.

PMID- 16452241
TI  - The anti-human leukocyte antigen-DR monoclonal antibody 1D09C3 activates the
      mitochondrial cell death pathway and exerts a potent antitumor activity in
      lymphoma-bearing nonobese diabetic/severe combined immunodeficient mice.
AB  - The fully human anti-HLA-DR antibody 1D09C3 has been shown to delay lymphoma cell
      growth in severe combined immunodeficient (SCID) mice. The present study was
      aimed at (a) investigating the mechanism(s) of 1D09C3-induced cell death and (b)
      further exploring the therapeutic efficacy of 1D09C3 in nonobese diabetic
      (NOD)/SCID mice. The chronic lymphocytic leukemia cell line JVM-2 and the mantle
      cell lymphoma cell line GRANTA-519 were used. Generation of reactive oxygen
      species (ROS) and mitochondrial membrane depolarization were measured by flow
      cytometry following cell incubation with dihydroethidium and TMRE, respectively.
      Western blot analysis was used to detect c-Jun-NH(2)-kinase (JNK) phosphorylation
      and apoptosis-inducing factor (AIF). NOD/SCID mice were used to investigate the
      activity of 1D09C3 in early- or advanced-stage tumor xenografts. In vitro, 1D09C3
      induced cell death involves a cascade of events, including ROS increase, JNK
      activation, mitochondrial membrane depolarization, and AIF release from
      mitochondria. Inhibition of JNK activity significantly reduced 1D09C3-induced
      apoptosis, indicating that 1D09C3 activity involves activation of the kinase. In
      vivo, 1D09C3 induces long-term disease-free survival in a significant proportion
      of tumor-bearing mice treated at an early stage of disease. Treatment of mice
      bearing advanced-stage lymphoma results in a highly significant prolongation of
      survival. These data show that 1D09C3 (a) exerts a potent antitumor effect by
      activating ROS-dependent, JNK-driven cell death, (b) cures the great majority of
      mice treated at an early-stage of disease, and (c) significantly prolongs
      survival of mice with advanced-stage disease.

PMID- 16452242
TI  - An essential role of antigen-presenting cell/T-helper type 1 cell-cell
      interactions in draining lymph node during complete eradication of class II
      negative tumor tissue by T-helper type 1 cell therapy.
AB  - Prior studies have shown that transfer of ovalbumin (OVA)-specific T helper type
      1 (Th1) cells into mice bearing MHC class II+ OVA-expressing tumor cells (A20
      OVA) causes complete tumor rejection. Here we show that, although Th1 cell
      therapy alone was not effective against MHC class II- OVA-expressing tumor cells
      (EG-7), treatment of mice bearing established EG-7 tumors by i.v. transfer of Th1
      cells combined with i.t. injection of the model tumor antigen OVA induced
      complete tumor rejection. Transferred Th1 cells enhanced the migration of tumor
      infiltrating antigen-presenting cells (APC) that had processed OVA into the
      draining lymph node (DLN). Although transferred Th1 cells were randomly
      distributed in DLN, distal LN, spleen, and tumor tissue, active proliferation of
      Th1 cells always initiated in DLN, where Th1 cells efficiently interacted with
      APC that presented OVA. In parallel, OVA-tetramer+ CTLs, showing EG-7-specific
      cytotoxicity, were highly induced in DLN and the local tumor site. The OVA
      tetramer+ CTL functioned systemically because two bilateral tumor masses were
      both completely rejected on treatment of one tumor. Furthermore, either active
      proliferation of transferred Th1 cells or generation of tetramer+ CTL was not
      induced in MHC class II-deficient mice and LN-deficient Aly/Aly mice. These
      results indicate that DLN is an indispensable organ for initiating active APC/Th1
      cell interactions, which is critical for inducing complete eradication of tumor
      mass by tumor-specific CTL.

PMID- 16452243
TI  - Identification and epitope enhancement of a PAX-FKHR fusion protein breakpoint
      epitope in alveolar rhabdomyosarcoma cells created by a tumorigenic chromosomal
      translocation inducing CTL capable of lysing human tumors.
AB  - Fusion proteins created by chromosomal translocations in tumors can create
      neoantigenic determinants at the breakpoint, which are unique to the tumor cells
      but shared by the vast majority of tumors of that histologic type. If the fusion
      protein is responsible for the malignant transformation, its expression cannot be
      lost by the tumor to escape immune responses against this tumor antigen. Here, we
      identify such a fusion protein breakpoint epitope in the PAX-FKHR fusion protein
      created by the t(2;13) translocation present in 80% of cases of alveolar
      rhabdomyosarcoma, a highly aggressive pediatric soft-tissue sarcoma. We use
      autologous dendritic cells pulsed with the RS10 breakpoint fusion peptide to
      raise a human CTL line from a normal healthy HLA-B7+ blood donor specific for
      this peptide. These CTLs are CD8+ (CD4-CD56-) and restricted by HLA-B7. These
      human peptide-specific CTL lyse human HLA-B7+ rhabdomyosarcoma tumor cells.
      Therefore, the fusion protein is endogenously processed to produce this natural
      epitope presented by HLA-B7 and thus this peptide is a bone fide human tumor
      antigen. We also define a substitution that increases the affinity for HLA-B7
      without loss of antigenicity. This epitope-enhanced peptide may serve as a
      candidate cancer vaccine for HLA-B7+ patients with alveolar rhabdomyosarcoma.

PMID- 16452244
TI  - Defining the role of prolactin as an invasion suppressor hormone in breast cancer
      cells.
AB  - Prolactin hormone (PRL) is well characterized as a terminal differentiation
      factor for mammary epithelial cells and as an autocrine growth/survival factor in
      breast cancer cells. However, this function of PRL may not fully signify its role
      in breast tumorigenesis. Cancer is a complex multistep progressive disease
      resulting not only from defects in cell growth but also in cell differentiation.
      Indeed, dedifferentiation of tumor cells is now recognized as a crucial event in
      invasion and metastasis. PRL plays a critical role in inducing/maintaining
      differentiation of mammary epithelial cells, suggesting that PRL signaling could
      serve to inhibit tumor progression. We show here that in breast cancer cells, PRL
      and Janus-activated kinase 2, a major kinase involved in PRL signaling, play a
      critical role in regulating epithelial-mesenchymal transformation (EMT), an
      essential process associated with tumor metastasis. Activation of the PRL
      receptor (PRLR), achieved by restoring PRL/JAK2 signaling in mesenchymal-like
      breast cancer cells, MDA-MB-231, suppressed their mesenchymal properties and
      reduced their invasive behavior. While blocking PRL autocrine function in
      epithelial-like breast cancer cells, T47D, using pharmacologic and genetic
      approaches induced mesenchymal-like phenotypic changes and enhanced their
      invasive propensity. Moreover, our results indicate that blocking PRL signaling
      led to activation of mitogen-activated protein kinase (extracellular signal
      regulated kinase 1/2) and transforming growth factor-beta/Smad signaling
      pathways, two major prometastatic pathways. Furthermore, our results indicate
      that following PRL/JAK2 inhibition, ERK1/2 activation precedes and is required
      for Smad2 activation and EMT induction in breast cancer cells. Together, these
      results highlight PRL as a critical regulator of epithelial plasticity and
      implicate PRL as an invasion suppressor hormone in breast cancer.

PMID- 16452245
TI  - Hepatocellular neoplasms induced by low-number pancreatic islet transplants in
      autoimmune diabetic BB/Pfd rats.
AB  - It has been shown that combined high local hyperinsulinism and hyperglycemia
      after low-number islet transplantation into the livers of streptozotocin-diabetic
      rats lead to the development of hepatocellular neoplasms but a substantial
      cocarcinogenic effect of genotoxic streptozotocin could not be ruled out
      completely. Thus, we herein investigated this model in BB/Pfd rats (n = 805; nine
      experimental groups), which develop spontaneous autoimmune diabetes similar to
      human type 1 diabetes. After low-number islet transplantation (n = 450), the
      liver acini downstream of the islets show insulin-induced alterations: massive
      glycogen and/or fat accumulation, translocation of the insulin receptor, decrease
      in glucose-6-phosphatase activity, increase in expression of insulin-like growth
      factor (IGF)-I, IGF-II/mannose-6-phosphate receptor, insulin receptor substrate
      1, Raf-1, and Mek-1, corresponding to clear cell preneoplastic foci of altered
      hepatocytes known from chemical hepatocarcinogenesis and identical to that in
      streptozotocin-diabetic Lewis rats. After 6 months, many altered liver acini
      progressed to other types of preneoplasias often accompanied by an overexpression
      of the glutathione-S transferase (placental form), IGF-I receptor, and
      transforming growth factor (TGF)-alpha. After 12 to 15 and 15 to 18 months, 52%
      and 100% of the animals showed one or multiple hepatocellular adenomas or
      hepatocellular carcinomas (HCCs), respectively. Conclusively, this study
      identifies combined hyperinsulinism and hyperglycemia as a carcinogenic mechanism
      for the development of HCCs in diabetic rats. Hepatocarcinogenesis is independent
      from additional genotoxic compounds (i.e., streptozotocin), but is primarily
      triggered by increased intracellular insulin signaling via pathways associated
      with cell growth and proliferation, such as the Ras-Raf-mitogen-activated protein
      kinase pathway and the IGF system, and secondarily involves other growth factors,
      such as TGF-alpha.

PMID- 16452246
TI  - Discovering clinical biomarkers of ionizing radiation exposure with serum
      proteomic analysis.
AB  - In this study, we sought to explore the merit of proteomic profiling strategies
      in patients with cancer before and during radiotherapy in an effort to discover
      clinical biomarkers of radiation exposure. Patients with a diagnosis of cancer
      provided informed consent for enrollment on a study permitting the collection of
      serum immediately before and during a course of radiation therapy. High
      resolution surface-enhanced laser desorption and ionization-time of flight (SELDI
      TOF) mass spectrometry (MS) was used to generate high-throughput proteomic
      profiles of unfractionated serum samples using an immobilized metal ion-affinity
      chromatography nickel-affinity chip surface. Resultant proteomic profiles were
      analyzed for unique biomarker signatures using supervised classification
      techniques. MS-based protein identification was then done on pooled sera in an
      effort to begin to identify specific protein fragments that are altered with
      radiation exposure. Sixty-eight patients with a wide range of diagnoses and
      radiation treatment plans provided serum samples both before and during ionizing
      radiation exposure. Computer-based analyses of the SELDI protein spectra could
      distinguish unexposed from radiation-exposed patient samples with 91% to 100%
      sensitivity and 97% to 100% specificity using various classifier models. The
      method also showed an ability to distinguish high from low dose-volume levels of
      exposure with a sensitivity of 83% to 100% and specificity of 91% to 100%. Using
      direct identity techniques of albumin-bound peptides, known to underpin the SELDI
      TOF fingerprints, 23 protein fragments/peptides were uniquely detected in the
      radiation exposure group, including an interleukin-6 precursor protein. The
      composition of proteins in serum seems to change with ionizing radiation
      exposure. Proteomic analysis for the discovery of clinical biomarkers of
      radiation exposure warrants further study.

PMID- 16452247
TI  - Soy phytochemicals prevent orthotopic growth and metastasis of bladder cancer in
      mice by alterations of cancer cell proliferation and apoptosis and tumor
      angiogenesis.
AB  - A role of dietary bioactive components in bladder cancer prevention is
      biologically plausible because most substances or metabolites are excreted
      through the urinary tract and are consequently in direct contact with the mucosa
      of the bladder. We first determined antigrowth activity of genistein against
      poorly differentiated 253J B-V human bladder cancer cells in vitro. Genistein
      inhibited the cell growth in a time- and dose-dependent manner via G(2)-M arrest,
      down-regulation of nuclear factor kappaB (NF-kappaB), and induction of apoptosis.
      We also evaluated both genistin, which is a natural form of genistein, and the
      isoflavone-rich soy phytochemical concentrate (SPC) on the growth and metastasis
      of 253J B-V tumors in an orthotopic tumor model. Mice treated with genistin and
      SPC had reduced final tumor weights by 56% (P < 0.05) and 52% (P < 0.05),
      respectively, associated with induction of tumor cell apoptosis and inhibition of
      tumor angiogenesis in vivo. In addition, SPC treatment, but not genistin
      treatment, significantly inhibited lung metastases by 95% (P < 0.01) associated
      with significant down-regulation of NF-kappaB expression in tumor tissues and
      reduction of circulating insulin-like growth factor-I levels, suggesting that SPC
      may contain other bioactive ingredients that have antimetastatic activity. The
      results from our studies suggest that further clinical investigation should be
      warranted to apply soy phytochemicals, such as SPC, as a potent prevention
      regimen for bladder cancer progression. This orthotopic human bladder tumor model
      also provides a clinically relevant experimental tool for assessing potential
      preventive activity of other dietary components against bladder tumor growth and
      metastasis.

PMID- 16452248
TI  - Red meat enhances the colonic formation of the DNA adduct O6-carboxymethyl
      guanine: implications for colorectal cancer risk.
AB  - Red meat is associated with increased risk of colorectal cancer and increases the
      endogenous formation of N-nitrosocompounds (NOC). To investigate the genotoxic
      effects of NOC arising from red meat consumption, human volunteers were fed high
      (420 g) red meat, vegetarian, and high red meat, high-fiber diets for 15 days in
      a randomized crossover design while living in a volunteer suite, where food was
      carefully controlled and all specimens were collected. In 21 volunteers, there
      was a consistent and significant (P < 0.0001) increase in endogenous formation of
      NOC with the red meat diet compared with the vegetarian diet as measured by
      apparent total NOC (ATNC) in feces. In colonic exfoliated cells, the percentage
      staining positive for the NOC-specific DNA adduct, O(6)-carboxymethyl guanine
      (O(6)CMG) was significantly (P < 0.001) higher on the high red meat diet. In 13
      volunteers, levels were intermediate on the high-fiber, high red meat diet. Fecal
      ATNC were positively correlated with the percentage of cells staining positive
      for O(6)CMG (r(2) = 0.56, P = 0.011). The presence of O(6)CMG was also shown in
      intact small intestine from rats treated with the N-nitrosopeptide N-acetyl-N'
      prolyl-N'-nitrosoglycine and in HT-29 cells treated with diazoacetate. This study
      has shown that fecal NOC arising from red meat include direct acting
      diazopeptides or N-nitrosopeptides able to form alkylating DNA adducts in the
      colon. As these O(6)CMG adducts are not repaired, and if other related adducts
      are formed and not repaired, this may explain the association of red meat with
      colorectal cancer.

PMID- 16452249
TI  - Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers.
AB  - High breast density as measured on mammograms is a strong risk factor for breast
      cancer in the general population, but its effect in carriers of germline BRCA1
      and BRCA2 mutations is unclear. We obtained mammograms from 206 female carriers
      of BRCA1 or BRCA2 mutations, 96 of whom were subsequently diagnosed with breast
      cancer and 136 relatives of carriers who were themselves noncarriers. We compared
      the mammographic densities of affected carriers (cases) and unaffected carriers
      (controls), and of mutation carriers and noncarriers, using a computer-assisted
      method of measurement and visual assessment by two observers. Analyses were
      adjusted for age, parity, body mass index, menopausal status, and hormone
      replacement therapy use. There was no difference in the mean percent density
      between noncarriers and carriers. Among carriers, increasing mammographic density
      was associated with an increased risk of breast cancer (P(trend) = 0.024). The
      odds ratio (OR; 95% confidence interval) for breast cancer associated with a
      density of > or =50% was 2.29 (1.23-4.26; P = 0.009). The OR did not differ
      between BRCA1 and BRCA2 carriers or between premenopausal and postmenopausal
      carriers. The results suggest that the distribution of breast density in BRCA1
      and BRCA2 carriers is similar to that in non-carriers. High breast density in
      carriers is associated with an increased risk of breast cancer, with the relative
      risk being similar to that observed in the general population. Use of
      mammographic density could improve individual risk prediction in carriers.

PMID- 16452250
TI  - Thiazolidinediones inhibit insulin-like growth factor-i-induced activation of
      p70S6 kinase and suppress insulin-like growth factor-I tumor-promoting activity.
AB  - Thiazolidinediones are a novel class of antidiabetic drugs that improve insulin
      sensitivity in type 2 diabetic patients. Recently, these compounds have also been
      shown to suppress tumor development in several animal models. The molecular basis
      for their antitumor action, however, is largely unknown. We report here that oral
      administration of thiazolidinediones (rosiglitazone and troglitazone) remarkably
      inhibited insulin-like growth factor-I (IGF-I)-promoted skin tumor development by
      73% in BK5.IGF-1 transgenic mice, although they were previously found to be
      ineffective in inhibiting UV- or chemically induced mouse skin tumorigenesis. The
      anti-IGF-I effect of troglitazone in mouse skin keratinocytes was due to, at
      least partially, inhibition of IGF-I-induced phosphorylation of p70S6 kinase
      (p70S6K) at Thr(389), a site specifically phosphorylated by mammalian target of
      rapamycin (mTOR). Troglitazone did not directly inhibit mTOR kinase activity as
      shown by mTOR in vitro kinase assay but rapidly activated AMP-activated protein
      kinase (AMPK) through a yet undefined peroxisome proliferator-activated receptor
      gamma-independent mechanism. Expression of a dominant-negative AMPK reversed the
      inhibitory effect of troglitazone on IGF-I-induced phosphorylation of p70S6K,
      suggesting that troglitazone inhibited IGF-I and p70S6K signaling through
      activation of AMPK. Collectively, these data suggest that thiazolidinediones
      specifically inhibit IGF-I tumor-promoting activity in mouse skin through
      activation of AMPK and subsequent inhibition of p70S6K.

PMID- 16452251
TI  - Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African
      American women.

PMID- 16452252
TI  - Metabotropic receptor-dependent long-term depression persists in the absence of
      protein synthesis in the mouse model of fragile X syndrome.
AB  - Fragile X syndrome (FXS), a form of human mental retardation, is caused by loss
      of function mutations in the fragile X mental retardation gene (FMR1). The
      protein product of FMR1, fragile X mental retardation protein (FMRP) is an RNA
      binding protein and may function as a translational suppressor. Metabotropic
      glutamate receptor-dependent long-term depression (mGluR-LTD) in hippocampal area
      CA1 is a form of synaptic plasticity that relies on dendritic protein synthesis.
      mGluR-LTD is enhanced in the mouse model of FXS, Fmr1 knockout (KO) mice,
      suggesting that FMRP negatively regulates translation of proteins required for
      LTD. Here we examine the synaptic and cellular mechanisms of mGluR-LTD in KO mice
      and find that mGluR-LTD no longer requires new protein synthesis, in contrast to
      wild-type (WT) mice. We further show that mGluR-LTD in KO and WT mice is
      associated with decreases in AMPA receptor (AMPAR) surface expression, indicating
      a similar postsynaptic expression mechanism. However, like LTD, mGluR-induced
      decreases in AMPAR surface expression in KO mice persist in protein synthesis
      inhibitors. These results are consistent with recent findings of elevated protein
      synthesis rates and synaptic protein levels in Fmr1 KO mice and suggest that
      these elevated levels of synaptic proteins are available to increase the
      persistence of LTD without de novo protein synthesis.

PMID- 16452253
TI  - Vesicle depletion and synaptic depression at a mammalian ribbon synapse.
AB  - We estimated the size of the readily releasable pool (RRP) of vesicles at a
      ribbon synapse in the rat retina by making paired voltage-clamp recordings from
      presynaptic rod bipolar cells (RBCs) and postsynaptic AII amacrine cells in an in
      vitro retinal slice preparation. The RRP at each active zone was estimated to
      constitute seven vesicles, in the range of estimated RRP sizes at conventional
      synapses. During sustained presynaptic Ca(2+) entry, the RRP could be released
      with a time constant of about 4 ms. This ribbon synapse exhibited pronounced
      paired-pulse depression (PPD), which was attributable primarily to vesicle
      depletion. Recovery from PPD was slow (tau approximately 4 s) but could be
      accelerated by increasing the duration of the depressing stimulus. The small RRP
      and very high release probability likely contribute to the transient
      characteristics of neurotransmission at RBC synapses.

PMID- 16452254
TI  - Cortical effects of brief daily periods of unrestricted vision during early
      monocular form deprivation.
AB  - Experiencing daily brief periods of unrestricted vision during early monocular
      form deprivation prevents or reduces the degree of resulting amblyopia. To gain
      insight into the neural basis for these "protective" effects, we analyzed the
      monocular and binocular response properties of individual neurons in the primary
      visual cortex (V1) of macaque monkeys that received intermittent unrestricted
      vision. Microelectrode-recording experiments revealed significant decreases in
      the proportion of units that were dominated by the treated eyes, and the
      magnitude of this ocular dominance imbalance was correlated with the degree of
      amblyopia. The sensitivity of V1 neurons to interocular spatial phase disparity
      was significantly reduced in all treated monkeys compared with normal adults.
      With unrestricted vision, however, there was a small but significant increase in
      overall disparity sensitivity. Binocular suppression was prevalent in monkeys
      with constant form deprivation but significantly reduced by the daily periods of
      unrestricted vision. If neurons exhibited consistent responses to stimulation of
      the treated eye, monocular response properties obtained by stimulation of the two
      eyes were similar. These results suggest that the observed protective effects of
      brief periods of unrestricted vision are closely associated with the ability of
      V1 neurons to maintain their functional connections from the deprived eye and
      that interocular suppression in V1 may play an important role in regulating
      synaptic plasticity of these monkeys.

PMID- 16452255
TI  - Somato-dendritic morphology predicts physiology for neurons that contribute to
      several kinds of limb movements.
AB  - It has been difficult to predict the behavioral roles of vertebrate CNS neurons
      based solely on their morphologies, especially for the neurons that control limb
      movements in adults. We examined the morphologies of spinal interneurons involved
      in limb movement control, using intracellular recording followed by Neurobiotin
      injection in the in vivo adult turtle spinal cord preparation. We report here the
      first description of a class of spinal interneurons whose somato-dendritic
      morphologies predict their robust activity during multiple forms of ipsilateral
      and contralateral fictive hindlimb scratching and fictive hindlimb withdrawal.
      These "transverse interneurons" or T cells have a mediolaterally elongated soma
      and a simple dendritic tree that is extensive in the transverse plane but
      restricted rostrocaudally. During fictive scratching, these cells display strong
      rhythmic modulation with higher peak firing rates than other scratch-activated
      interneurons. These higher peak firing rates are at least partly caused by T
      cells having larger phase-locked membrane potential oscillations and narrower
      action potentials with briefer afterhyperpolarizations than other scratch
      activated interneurons. Many T cells have axon terminal arborizations in the
      ventral horn of the spinal cord hindlimb enlargement. Identification of this
      morphological and physiological class of spinal interneurons should facilitate
      further exploration of the mechanisms of hindlimb motor pattern selection and
      generation.

PMID- 16452256
TI  - Dopamine D1/5 receptor modulation of firing rate and bidirectional theta burst
      firing in medial septal/vertical limb of diagonal band neurons in vivo.
AB  - The medial septum/vertical limb of diagonal band complex (MS/vDB) consists of
      cholinergic, GABAergic, and glutamatergic neurons that project to the hippocampus
      and functionally regulate attention, memory, and cognitive processes. Using
      tyrosine hydroxlase (TH) immunocytochemistry and dark-field light microscopy, we
      found that the MS/vDB is innervated by a sparse network of TH-immunoreactive
      (putative catecholaminergic) terminals. MS/vDB neurons are known to fire in
      rhythmic theta burst frequency of 3-7 Hz to pace hippocampal theta rhythm.
      Extracellular single-unit recording in theta and non-theta firing MS/vDB neurons
      and antidromically identified MS/vDB-hippocampal neurons were made in urethan
      anesthetized rats. Tail-pinch noxious stimuli and ventral tegmental area (VTA)
      stimulation (20 Hz) evoked spontaneous theta burst firing in MS/vDB neurons.
      Systemic D1/5 antagonists SCH23390 or SCH39166 (0.1 mg/kg iv) alone suppressed
      the spontaneous theta bursts, suggesting a tonic facilitatory endogenous dopamine
      D1 "tone" that modulates theta bursts in vivo. Activation of D1/5 receptor by
      dihydrexidine (10 mg/kg iv) led to an increase in mean firing rate in 60% of all
      theta and non-theta MS/vDB neurons with an increase in the number of theta bursts
      and spikes/burst in theta cells. In strong theta firing MS/vDB neurons, D1/5
      receptor stimulation suppressed the occurrence of theta burst firing, whereas the
      overall increase in spontaneous mean firing rate remained. In low baseline theta
      MS/vDB neurons D1/5 receptor stimulation increases the occurrence of theta bursts
      along with a net increase in mean firing rate. Atropine injection consistently
      disrupts theta burst pattern and reduced the time spent in theta firing.
      Collectively, these data suggest that dopamine D1/5 stimulation enhances the mean
      firing rate of most MS/vDB neurons and also provides a state-dependent
      bidirectional modulation of theta burst occurrence. Some of these MS/vDB neurons
      may be cholinergic or GABAergic that may indirectly regulate theta rhythm in the
      hippocampus.

PMID- 16452257
TI  - Hippocampal network hyperactivity after selective reduction of tonic inhibition
      in GABA A receptor alpha5 subunit-deficient mice.
AB  - Functionally, gamma-aminobutyric acid receptor (GABAR)-mediated inhibition can be
      classified as phasic (synaptic) and tonic (extrasynaptic). The GABARs underlying
      tonic inhibition assemble from subunits different from those responsible for
      phasic inhibition. We wanted to assess the excitability of hippocampal pyramidal
      cell (PC) networks following a selective impairment of tonic inhibition. This is
      difficult to accomplish by pharmacological means. Because the GABAR alpha5
      subunits mostly mediate the tonic inhibition in CA1 and CA3 PCs, we quantified
      changes in tonic inhibition and examined network excitability in slices of adult
      gabra5-/- mice. In gabra5-/- CA1 and CA3 PCs tonic inhibitory currents were 60
      and 53%, respectively, of those recorded in wild type (WT), with no alterations
      in phasic inhibition. The amount of tonic inhibition recorded in slices was
      significantly affected by the method of slice storage (interface or submerged
      chamber). Field recordings in gabra5-/- CA3 pyramidal layer showed an increased
      network excitability that was decreased by the GABAR agonist muscimol at a
      concentration that restored the tonic inhibition of gabra5-/- PCs to the WT level
      without altering phasic inhibition. Through a battery of pharmacological
      experiments, we have identified delta subunit-containing GABARs as the mediators
      of the residual tonic inhibition in gabra5-/- PCs. Our study is consistent with
      an important role of tonic inhibition in the control of hippocampal network
      excitability and highlights selective enhancers of tonic inhibition as promising
      therapeutic approaches for diseases involving network hyperexcitability.

PMID- 16452258
TI  - Synaptic and somatic effects of axotomy in the intact, innervated rat sympathetic
      neuron.
AB  - A biophysical description of the axotomized rat sympathetic neuron is reported,
      obtained by the two-electrode voltage-clamp technique in mature, intact superior
      cervical ganglia in vitro. Multiple aspects of neuron functioning were tested.
      Synaptic conductance activated by the whole presynaptic input decreased to 29% of
      the control value (0.92 muS per neuron) 1 day after axotomy and to 18% after 3
      days. Despite the decrease in amplitude of the macroscopic current, miniature
      excitatory postsynaptic current (mEPSC) mean conductance, acetylcholine (ACh)
      equilibrium potential, and EPSC decay time constant were unaffected. Synaptic
      efficacy was tested during paired-pulse or maintained stimulation (5, 10, and 15
      Hz, 10-s duration). Quantal release in axotomized neurons was preserved during
      the tetanus despite the reduction of the initial EPSC amplitude, suggesting that
      ACh secretion depended on the number of surviving synapses; each of them
      exhibited dynamic behavior during trains similar to that of normal synapses.
      Facilitation of EPSC amplitude was noted in 2-day axotomized neurons during the
      first few impulses in the train. Voltage-dependent potassium currents (the
      delayed I(KD) and the transient I(A)) exhibited an early drastic decrease in peak
      amplitude; these effects persisted 7 days after axotomy. Marked changes in I(A)
      kinetics occurred after injury: the steady-state inactivation curve shifted by up
      to +17 mV toward positive potentials and the voltage sensitivity of inactivation
      removal became steeper. I(A) impairment was reflected in a reduced inward
      threshold charge for discharge and reduced spike repolarization rate. Synaptic
      and somatic data were applied in a mathematical model to describe the progressive
      decrease in the safety factor, and the eventual failure of ganglionic
      transmission after axotomy.

PMID- 16452259
TI  - Does unilateral pedaling activate a rhythmic locomotor pattern in the nonpedaling
      leg in post-stroke hemiparesis?
AB  - Recent investigation in persons with clinically complete spinal cord injury has
      revealed that locomotor activity in one limb can activate rhythmic locomotor
      activity in the opposite limb. Although our previous research has demonstrated
      profound influences of the nonparetic limb on paretic limb motor activity
      poststroke, the potency of interlimb pathways for increasing recruitment of the
      paretic limb motor pattern is unknown. This experiment tested whether there is an
      increased propensity for rhythmic motor activity in one limb (pedaling limb) to
      induce rhythmic motor activity in the opposite limb (test limb) in persons
      poststroke. Forty-nine subjects with chronic poststroke hemiparesis and twenty
      controls pedaled against a constant mechanical load with their pedaling leg while
      we recorded EMG and pedal forces from the test leg. For the experimental
      conditions, subjects were instructed to either pedal with their test leg
      (bilateral pedaling) or rest their test leg while it was either stationary or
      moved anti-phased (unilateral pedaling). In persons poststroke, unilateral
      pedaling activated a complete pattern of rhythmic alternating muscle activity in
      the nonpedaling, test leg. This effect was most clearly demonstrated in the most
      severely impaired individuals. In most of the control subjects, unilateral
      pedaling activated some muscles in the nonpedaling leg weakly, if at all. We
      propose that, ipsilateral excitatory pathways associated with contralateral
      pedaling in control subjects are increasingly up-regulated in both legs in
      persons with hemiparesis as a function of increased hemiparetic severity. This
      enhancement of interlimb pathways may be of functional importance since
      contralateral pedaling induced a complete motor pattern of similar amplitude to
      the bilateral pattern in both the paretic and nonparetic leg of the subjects with
      severe hemiparesis.

PMID- 16452260
TI  - Atypical phenotypes from flatworm Kv3 channels.
AB  - Divergence of the Shaker superfamily of voltage-gated (Kv) ion channels early in
      metazoan evolution created numerous electrical phenotypes that were presumably
      selected to produce a wide range of excitability characteristics in neurons,
      myocytes, and other cells. A comparative approach that emphasizes this early
      radiation provides a comprehensive sampling of sequence space that is necessary
      to develop generally applicable models of the structure-function relationship in
      the Kv potassium channel family. We have cloned and characterized two Shaw-type
      potassium channels from a flatworm (Notoplana atomata) that is arguably a
      representative of early diverging bilaterians. When expressed in Xenopus oocytes,
      one of these cloned channels, N.at-Kv3.1, exhibits a noninactivating, outward
      current with slow opening kinetics that are dependent on both the holding
      potential and the activating potential. A second Shaw-type channel, N.at-Kv3.2,
      has very different properties, showing weak inward rectification. These results
      demonstrate that broad phylogenetic sampling of proteins of a single family will
      reveal unexpected properties that lead to new interpretations of structure
      function relationships.

PMID- 16452261
TI  - Doublet discharges in motoneurons of young and older adults.
AB  - The purpose of this study was to investigate the occurrence of motor unit doublet
      discharges in young and older individuals at different rates of increasing force.
      Participants included eight young (21.9 +/- 3.56 yr) and eight older (74.1 +/-
      8.79 yr) individuals, with equal numbers of males and females in each group.
      Motor unit activity was recorded from the tibialis anterior during isometric
      dorsiflexion using a four-wire needle electrode. Subjects performed three ramp
      contractions from zero to 50% maximal voluntary contraction (MVC) force at each
      of three rates: 10, 30, and 50% MVC/s. Overall, the occurrence of doublets was
      significantly higher in the young than in the older individuals. However, neither
      group showed differences in the occurrence of doublets across the three rates of
      force production. Doublet firings were observed in 45.6 (young) and 35.1% (old)
      of motor units at 10% MVC/s; 48.6 (young) and 22.5% (old) of motor units at 30%
      MVC/s; and 48.4 (young) and 31.4% (old) at 50% MVC/s. The maximal firing rate was
      significantly higher and the force at which the motor units were recruited was
      significantly lower for those units that fired doublets than those that did not.
      The force at which doublets occurred ranged from 3.42 to 50% MVC in the young
      subjects and from 0 (force onset) to 50% MVC in the older subjects. The results
      of this study suggest that the occurrence of doublets is dependent on both motor
      unit firing rate and force level. The lower incidence of doublets in older
      individuals may be attributable to changes in the intrinsic properties of the
      motoneurons with aging, which appear to play a role in doublet discharges.

PMID- 16452262
TI  - Inflammation-susceptible Lewis rats show less sensitivity than resistant Fischer
      rats in the formalin inflammatory pain test and with repeated thermal testing.
AB  - Comparisons between Lewis and Fischer inbred strains of rats are used frequently
      to study the effect of inherent differences in function of the hypothalamic
      pituitary-adrenal axis on pain-relevant traits, including differential
      susceptibility to chronic inflammatory disease and differential responsiveness to
      analgesic drugs. Increasing use of genetic models including transgenic knockout
      mice and inbred strains of rodents has raised our awareness of, and the
      importance of, thorough characterization (or phenotyping) of the strains of
      rodents being compared. Furthermore, genetic variability in analgesic sensitivity
      is correlated with, and may be caused by, genetically determined baseline
      sensitivity. Thus in this study, baseline inflammatory and thermal nociceptive
      sensitivities were measured in awake male and female Lewis and Fischer rats to
      examine whether the results could explain relevant strain differences reported in
      the literature. The effect of maternal separation was also examined and no effect
      was found on nociceptive sensitivity, corticosterone responses, or the
      development of adjuvant-induced arthritis, a model of rheumatoid arthritis. Lewis
      rats and female rats were more sensitive to thermal nociception in the tail
      withdrawal test (mean of 3 trials) than Fischer rats and male rats, respectively.
      Unexpectedly, the more inflammation-susceptible Lewis rats were less sensitive in
      the formalin inflammatory nociception test, and showed a significant decrease in
      sensitivity with repeated thermal nociceptive testing, whereas Fischer rats did
      not. These results affect the interpretation of previously observed results.
      Further study of the underlying mechanisms and the relevance to differential
      susceptibility to chronic inflammation is warranted.

PMID- 16452263
TI  - Role of an identified looming-sensitive neuron in triggering a flying locust's
      escape.
AB  - Flying locusts perform a characteristic gliding dive in response to predator
      sized stimuli looming from one side. These visual looming stimuli trigger trains
      of spikes in the descending contralateral movement detector (DCMD) neuron that
      increase in frequency as the stimulus gets nearer. Here we provide evidence that
      high-frequency (>150 Hz) DCMD spikes are involved in triggering the glide: the
      DCMD is the only excitatory input to a key gliding motor neuron during a loom;
      DCMD-mediated EPSPs only summate significantly in this motor neuron when they
      occur at >150 Hz; when a looming stimulus ceases approach prematurely, high
      frequency DCMD spikes are removed from its response and the occurrence of gliding
      is reduced; and an axon important for glide triggering descends in the nerve cord
      contralateral to the eye detecting a looming stimulus, as the DCMD does. DCMD
      recordings from tethered flying locusts showed that glides follow high-frequency
      spikes in a DCMD, but analyses could not identify a feature of the DCMD response
      alone that was reliably associated with glides in all trials. This was because,
      for a glide to be triggered, the high-frequency spikes must be timed
      appropriately within the wingbeat cycle to coincide with wing elevation. We
      interpret this as flight-gating of the DCMD response resulting from rhythmic
      modulation of the flight motor neuron's membrane potential during flight. This
      means that the locust's escape behavior can vary in response to the same looming
      stimulus, meaning that a predator cannot exploit predictability in the locust's
      collision avoidance behavior.

PMID- 16452264
TI  - Operative and nonoperative treatments of medial collateral ligament rupture with
      early anterior cruciate ligament reconstruction: a prospective randomized study.
AB  - BACKGROUND: The apparent consensus is that solitary medial collateral ligament
      rupture can be treated nonoperatively, but treatment of severe combined ruptures
      of the medial collateral ligament and anterior cruciate ligament remains
      controversial. HYPOTHESES: Nonoperative and early operative treatments of grade
      III medial collateral ligament rupture lead to similar results when the anterior
      cruciate ligament is reconstructed in the early phase. STUDY DESIGN: Randomized
      controlled clinical trial; Level of evidence, 1. METHODS: Forty-seven consecutive
      patients with combined anterior cruciate ligament and grade III medial collateral
      ligament injuries were randomized into 2 groups. The medial collateral ligament
      injury was treated operatively in group 1 (n = 23) and non-operatively in group 2
      (n = 24). In both groups, the anterior cruciate ligament injury was treated with
      early reconstruction, using bone-patellar tendon-bone graft and interference
      screw. Two years postoperatively, knee stability was measured with a KT-1000
      arthrometer and Telos valgus radiography and knee extension strength with a
      Biodex dynamometer and a 1-legged hop test. An International Knee Documentation
      Committee evaluation form and Lysholm score were completed. RESULTS: All 47
      patients were available for clinical evaluation for a mean of 27 months (range,
      20-37 months) after surgery. There were no statistically significant differences
      between the 2 groups with respect to subjective function of the knee,
      postoperative stability, range of motion, muscle power, return to activities,
      Lysholm score, and overall International Knee Documentation Committee evaluation.
      The subjective outcome and Lysholm score were good and anteroposterior knee
      stability excellent in both groups. CONCLUSION: Nonoperative and operative
      treatments of medial collateral ligament injuries lead to equally good results.
      Medial collateral ligament ruptures need not be treated operatively when the
      anterior cruciate ligament is reconstructed in the early phase.

PMID- 16452265
TI  - Comparison of fresh osteochondral autografts and allografts: a canine model.
AB  - BACKGROUND: Osteochondral autografts and allografts have been widely used in the
      treatment of isolated grade IV articular cartilage lesions of the knee. However,
      the authors are not aware of any study that has prospectively compared fresh
      osteochondral autografts to fresh allografts with regard to imaging,
      biomechanical testing, and histology. HYPOTHESIS: The imaging, biomechanical
      properties, and histologic appearance of fresh osteochondral autograft and fresh
      allograft are similar with respect to bony incorporation into host bone,
      articular cartilage composition, and biomechanical properties. STUDY DESIGN:
      Controlled laboratory study. METHODS: Eighteen adult dogs underwent bilateral
      knee osteochondral graft implantation after creation of an Outerbridge grade IV
      cartilage defect. One knee received an autograft, and the contralateral knee
      received a fresh allograft. Nine dogs were sacrificed at 3 months, and 9 dogs
      were sacrificed at 6 months. Graft analysis included gross examination,
      radiographs, magnetic resonance imaging, biomechanical testing, and histology.
      RESULTS: Magnetic resonance imaging demonstrated excellent bony incorporation of
      both autografts and allografts. Biomechanical testing demonstrated no significant
      difference between autografts versus allografts versus control at 3 or 6 months
      (P = .36-.91). A post hoc calculation showed 80% power to detect a 30% difference
      between allograft and control. Histologic examination showed normal cartilage
      structure for both autografts and allografts. CONCLUSION: Fresh osteochondral
      autograft and fresh allograft tissues are not statistically different with
      respect to bony incorporation, articular cartilage composition, or biomechanical
      properties up to 6 months after implantation. CLINICAL RELEVANCE: The use of
      fresh allograft tissue to treat osteochondral defects eliminates morbidity
      associated with harvesting autograft tissue without compromising the results of
      the surgical procedure.

PMID- 16452266
TI  - Popliteus strain causing tibial nerve palsy with a permanent partial deficit: a
      case report.

PMID- 16452267
TI  - Midterm and long-term results after arthroscopic suture repair of isolated,
      longitudinal, vertical meniscal tears in stable knees.
AB  - BACKGROUND: The long-term outcome of meniscal suture repair has not been firmly
      established. PURPOSE: To compare the midterm and long-term functional and
      radiographic outcome of meniscal suture repairs with the natural history of the
      uninjured knees of each of a cohort of patients. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: Eighty-eight patients with an isolated,
      longitudinal, vertical tear of one of the menisci within a stable knee were
      arthroscopically treated with a meniscal suture repair. No patient had a previous
      surgery, and no additional chondral lesion was present. The opposite knee of each
      patient was uninjured. Both knees of each patient were examined clinically and
      radiographically in a retrospective follow-up 5 to 17 years (mean, 10 years)
      after meniscal repair. RESULTS: Three patients with postoperative complications
      and 21 patients whose menisci had to be removed because of rerupture were
      excluded from further evaluation for purposes of this study. The remaining 64
      patients reached a mean Tegner activity level of 6 points (range, 3-10 points)
      and achieved a mean Lysholm score of 94 points (range, 26-100 points).
      Osteoarthritis was found in 46 of the injured knees, compared with 27 of the
      uninjured knees (P = .004). However, 42 of the patients had no difference in the
      grade of osteoarthritis between the injured knee and the uninjured knee, 19 had a
      difference of 1 grade, 2 had a difference of 2 grades, and 1 had a difference of
      3 grades. CONCLUSION: Arthroscopic meniscal repair for isolated longitudinal
      meniscal injuries in stable knees yields favorable functional results, but its
      effects on the risk of secondary osteoarthritis are not clear.

PMID- 16452268
TI  - Sports and recreation activity of ankle arthritis patients before and after total
      ankle replacement.
AB  - BACKGROUND: Total ankle replacement is a possible treatment for ankle arthritis;
      however, participation in sports after this procedure has not yet been analyzed.
      HYPOTHESES: There is a significant increase of sports activity after total ankle
      replacement in patients with arthritis. There is a significant correlation
      between sports activity and American Orthopaedic Foot and Ankle Society hindfoot
      score in patients after total ankle replacement. STUDY DESIGN: Case series; Level
      of evidence, 4. METHODS: A clinical evaluation was performed preoperatively and
      at follow-up after total ankle replacement in 147 patients (152 ankles) with
      ankle arthritis (mean age, 59.6 years; range, 28-86 years). Ankle arthritis
      origin, patient satisfaction, range of motion, American Orthopaedic Foot and
      Ankle Society hindfoot score, radiologic assessment, and rate, level, and type of
      sports activity were documented at both evaluations. The mean follow-up was 2.8
      years (range, 2-4 years). RESULTS: Preoperative diagnosis was posttraumatic
      osteoarthritis in 115 cases (76%). At total ankle replacement follow-up,
      excellent and good outcomes were reported in 126 cases (83%); 105 cases (69%)
      were pain free. The mean range of motion pre-operatively was 21 degrees (range, 0
      degrees -45 degrees ); after total ankle replacement, it was 35 degrees (range,
      10 degrees -55 degrees ; P < .05). The preoperative American Orthopaedic Foot and
      Ankle Society score was 36 points; after total ankle replacement, it was 84
      points (P < .001). Before surgery, 36% of the patients were active in sports;
      after surgery, this percentage rose to 56% (P < .001). After total ankle
      replacement, sports-active patients showed a significantly higher hindfoot score
      than did patients not active in sports: 88 versus 79 points (P < .001). The 3
      most frequent sports activities were hiking, biking, and swimming. CONCLUSION:
      There was a significant increase of sports activity by treating ankle arthritis
      patients with total ankle replacement. Sports-active total ankle replacement
      patients showed better functional results than did inactive ones.

PMID- 16452269
TI  - Risk factors for shoulder and elbow injuries in adolescent baseball pitchers.
AB  - BACKGROUND: There is little evidence supporting current safety recommendations
      for adolescent pitchers. HYPOTHESIS: Pitching practices of adolescent pitchers
      without history of arm injury will be significantly different from those of
      adolescent pitchers who required shoulder or elbow surgery. STUDY DESIGN: Case
      control study; Level of evidence, 3. METHODS: Ninety-five adolescent pitchers who
      had shoulder or elbow surgery and 45 adolescent pitchers who never had a
      significant pitching-related injury completed a survey. Responses were compared
      between the 2 groups using t tests and chi(2) analyses. Multivariable logistic
      regression models were developed to identify the risk factors. RESULTS: The
      injured group pitched significantly more months per year, games per year, innings
      per game, pitches per game, pitches per year, and warm-up pitches before a game.
      These pitchers were more frequently starting pitchers, pitched in more showcases,
      pitched with higher velocity, and pitched more often with arm pain and fatigue.
      They also used anti-inflammatory drugs and ice more frequently to prevent an
      injury. Although the groups were age matched, the injured group was taller and
      heavier. There were no significant differences regarding private pitching
      instruction, coach's chief concern, pitcher's self-rating, exercise programs,
      stretching practices, relieving frequency, pitch type frequency, or age at which
      pitch types were first thrown. CONCLUSION: Pitching practices were significantly
      different between the groups. The factors with the strongest associations with
      injury were overuse and fatigue. High pitch velocity and participation in
      showcases were also associated with increased risk for injury. CLINICAL
      RELEVANCE: New recommendations were made based on these results. Adherence to the
      recommendations may reduce the incidence of significant injury to adolescent
      pitchers.

PMID- 16452270
TI  - The effect of the inferior capsular shift on shoulder intra-articular pressure: a
      cadaveric study.
AB  - BACKGROUND: The inferior capsular shift procedure is commonly performed for
      multidirectional instability of the shoulder with excellent clinical results.
      HYPOTHESIS: The mechanism of this procedure is to increase shoulder stability by
      changing the responsiveness of intra-articular pressure to downward loading.
      STUDY DESIGN: Controlled laboratory study. METHODS: In 7 fresh-frozen cadaveric
      shoulders, inferior capsular shift was simulated by imbricating the anterior and
      posterior capsule using clamps. The position was monitored using an
      electromagnetic tracking device with the glenohumeral joint capsule intact,
      imbricated anteriorly, or imbricated anteriorly and posteriorly and with the
      inferior load of 0, 0.5, or 1.0 kg. Simultaneously, intra-articular pressure was
      monitored using a pressure transducer. Saline was injected into the glenohumeral
      joint to measure capsular volume. The capsule was vented, and the position was
      again measured. RESULTS: Intra-articular pressure was -71 +/- 19, -221 +/- 70,
      and -366 +/- 73 cm H(2)O with 0, 0.5, and 1.0 kg of load, respectively, with the
      capsule intact. With anterior imbrication, intra-articular pressure decreased to 
      79 +/- 10, -274 +/- 103, and -460 +/- 135 cm H(2)O, respectively, and with
      anterior and posterior imbrication, intra-articular pressure further decreased to
      -87 +/- 16, -308 +/- 74, and -548 +/- 39 cm H(2)O, respectively. The volume of
      the intact shoulder (36 +/- 9 mL) significantly decreased to 27 +/- 7 mL (75%)
      with anterior imbrication and to 15 +/- 5 mL (42%) with anterior and posterior
      imbrications (P = .0001). Before venting the capsule, inferior displacement was
      5% of the vertical length of the glenoid, even with 1.0 kg of load with any
      capsular conditions. After venting, the humeral head dislocated inferiorly in all
      shoulders, even after imbrications. CONCLUSION: The inferior capsular shift
      procedure decreases joint volume and increases responsiveness of intra-articular
      pressure to downward loading. CLINICAL RELEVANCE: Biomechanical data provide
      scientific background to the commonly performed procedures of inferior capsular
      shift and thermal capsular shrinkage.

PMID- 16452271
TI  - Recurrent subluxation of the peroneal tendons.
AB  - BACKGROUND: Recurrent peroneal tendon subluxation is uncommon. HYPOTHESIS: The
      authors tested the null hypothesis that there are no differences between
      preoperative and postoperative status after anatomical repair of the superior
      peroneal retinaculum. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      In the period 1996 to 2001, the authors operated on 14 patients (all men; mean
      age, 25.3 +/- 6.3 years; range, 18-37 years) with traumatic recurrent unilateral
      peroneal tendon subluxation, with a follow-up of 38 +/- 3 months (range, 22-47
      months). RESULTS: No patient experienced a further episode of peroneal tendon
      subluxation, and all had returned to their normal activities. Maximum calf
      circumference, functional ability, peak torque, total work, and mean power of
      plantar flexion were always lower in the operated leg, but the differences did
      not reach statistical significance. The American Orthopaedic Foot and Ankle
      Society Ankle-Hindfoot Scale score increased significantly from 54.3 +/- 11.4 to
      94.5 +/- 6.4 (P = .03), with 5 patients reporting a fully normal ankle.
      CONCLUSION: If an anatomical approach is used, reattachment of the superior
      retinaculum is a most appropriate technique. It returns patients to a high level
      of physical activity and gives a high rate of satisfactory results both
      objectively and subjectively. Randomized control trials may be the way forward in
      determining the best surgical management method. However, the relative rarity of
      the condition and the large number of techniques make such a study difficult.

PMID- 16452273
TI  - PREP as a teaching tool.

PMID- 16452272
TI  - Anatomical study of the femoral and tibial insertions of the anteromedial and
      posterolateral bundles of human anterior cruciate ligament.
AB  - BACKGROUND: Recently, anatomical anterior cruciate ligament reconstruction with 2
      bundle reconstruction has been proposed. Few previous publications have mentioned
      anatomical measurements of the insertions of these bundles. PURPOSE: To determine
      the precise anatomical measurements of the femoral and tibial insertions for
      anteromedial and posterolateral bundles of anterior cruciate ligament grafts.
      STUDY DESIGN: Descriptive laboratory study. METHODS: Thirty-two femurs and 31
      tibias were selected. The anterior cruciate ligament was divided into
      anteromedial and posterolateral bundles to the insertion footprint. Six
      measurements of the femoral insertion and 4 measurements of the tibial insertion
      were examined. Locations of the femoral insertions were examined using lateral
      radiographs of the femur. RESULTS: The distance between the center of the femoral
      insertions of the anteromedial and posterolateral bundles and the posterior
      margin of the lateral femoral condyle averaged 7.6 and 7.0 mm, respectively. The
      distance between the center of the femoral insertions of the anteromedial and
      posterolateral bundles to the intercondylar roof averaged 4.1 and 11.3 mm,
      respectively. The sagittal distance between the center of the tibial insertions
      of the anteromedial and posterolateral bundles from the anterior margin of the
      tibial articular cartilage averaged 13.0 and 14.7 mm, respectively. The distance
      from the lateral margin of the articular cartilage of the tibial plateau to the
      center of the tibial insertions of the anteromedial and posterolateral bundles
      averaged 44.2% and 52.4% of the total widest width of the tibial plateau,
      respectively. On the lateral radiograph of femoral condyles, the center of the
      anteromedial bundle was located at 31.9% from the posterior margin of the femoral
      condyle and 26.9% from the roof, and that of the posterolateral bundle was
      located at 39.8% from the posterior margin of the femoral condyle and 53.2% from
      the roof. CLINICAL RELEVANCE: It is important to know the precise anatomy of
      anterior cruciate ligament bundles when performing reconstruction and to evaluate
      anterior cruciate ligament reconstruction surgery on an anatomical basis.

PMID- 16452274
TI  - Vitamins.

PMID- 16452275
TI  - Separation anxiety disorder and school refusal in children and adolescents.

PMID- 16452276
TI  - Consultation with the specialist: dysmenorrhea.

PMID- 16452277
TI  - Index of suspicion.

PMID- 16452278
TI  - Preformed reggie/flotillin caps: stable priming platforms for macrodomain
      assembly in T cells.
AB  - T cell activation after contact with an antigen-presenting cell depends on the
      regulated assembly of the T cell receptor signaling complex, which involves the
      polarized assembly of a stable, raft-like macrodomain surrounding engaged T cell
      receptors. Here we show that the preformed reggie/flotillin caps present in
      resting T cells act as priming platforms for macrodomain assembly. Preformed
      reggie-1/flotillin-2 caps are exceptionally stable, as shown by fluorescence
      recovery after photobleaching (FRAP). Upon T cell stimulation, signaling
      molecules are recruited to the stable reggie/flotillin caps. Importantly, a trans
      negative reggie-1/flotillin-2 deletion mutant, which interferes with assembly of
      the preformed reggie/flotillin cap, impairs raft polarization and macrodomain
      formation after T cell activation. Accordingly, expression of the trans-negative
      reggie-1 mutant leads to the incorrect positioning of the guanine nucleotide
      exchange factor Vav, resulting in defects in cytoskeletal reorganization. Thus,
      the preformed reggie/flotillin caps are stable priming platforms for the assembly
      of multiprotein complexes controlling actin reorganization during T cell
      activation.

PMID- 16452279
TI  - Medicaid and family wealth transfer.
AB  - PURPOSE: This study examines whether the relationship between making familial
      wealth transfers and becoming a Medicaid recipient sheds light on the current
      debate about Medicaid estate planning, whereby some elders transfer their assets
      to their families to qualify for Medicaid. DESIGN AND METHODS: Using the Health
      and Retirement Study, we tracked a national sample of community-based elders who
      did not receive Medicaid at the 1993 baseline interview but became Medicaid
      recipients during a 10-year time period and examined wealth transfers for these
      new Medicaid beneficiaries. RESULTS: Among elders aged 70 or older who did not
      receive Medicaid in 1993, 16.4% became Medicaid recipients over 10 years. Among
      these new Medicaid recipients, 17.9% transferred their wealth to family members
      before receiving Medicaid benefits, with an average transfer amount of $8,507
      during the 2 years prior to receiving Medicaid benefits. In addition, 15.2% of
      community-residing elders entered a nursing home during the 10-year period, and
      26.3% of these were covered by Medicaid. Of these new Medicaid recipients living
      in nursing homes, 12.6% transferred wealth to their families in the mean amount
      of $4,112. IMPLICATIONS: Familial wealth transfers do occur before changes in
      Medicaid eligibility in a small, but nontrivial, number of cases, but the amount
      transferred is modest, especially among nursing home residents. This finding
      implies that policies to reduce Medicaid long-term-care expenditures by limiting
      such transfers may not be very effective.

PMID- 16452280
TI  - Depression treatment preferences in older primary care patients.
AB  - PURPOSE: For depressed older primary care patients, this study aimed to examine
      (a) characteristics associated with depression treatment preferences; (b)
      predictors of receiving preferred treatment; and (c) whether receiving preferred
      treatment predicted satisfaction and depression outcomes. DESIGN AND METHODS:
      Data are from 1,602 depressed older primary care patients who participated in a
      multisite, randomized clinical trial comparing usual care to collaborative care,
      which offered medication and counseling for up to 12 months. Baseline assessment
      included demographics, depression, health information, prior depression
      treatment, potential barriers, and treatment preferences (medication,
      counseling). At 12 months, services received, satisfaction, and depression
      outcomes were assessed. RESULTS: More patients preferred counseling (57%) than
      medication (43%). Previous experience with a treatment type was the strongest
      predictor of preference. In addition, medication preference was predicted by male
      gender and diagnosis of major depression (vs dysthymia). The collaborative care
      model greatly improved access to preferred treatment, especially for counseling
      (74% vs 33% in usual care). Receipt of preferred treatment did not predict
      satisfaction or depression outcomes; these outcomes were most strongly impacted
      by treatment condition. IMPLICATIONS: Many depressed older primary care patients
      desire counseling, which is infrequently available in usual primary care.
      Discussion of treatment preferences should include an assessment of prior
      treatment experiences. A collaborative care model that increases collaboration
      between primary care and mental health professionals can increase access to
      preferred treatment. If preferred treatment is not available, collaborative care
      still results in good satisfaction and depression outcomes.

PMID- 16452281
TI  - Concepts and causation of depression: a cross-cultural study of the beliefs of
      older adults.
AB  - PURPOSE: This U.K. study explored how older adults with depression (treated and
      untreated) and the general older population conceptualize depression. A
      multicultural approach was used that incorporated the perspectives of Black
      Caribbean, South Asian, and White British older adults. The study sought to
      explore and compare beliefs about the nature and causes of depression, and to
      suggest ways in which these beliefs act to facilitate or deter older people from
      accessing treatment. DESIGN AND METHODS: One hundred and ten in-depth separate
      interviews were conducted for 45 White British, 33 South Asian, and 32 Black
      Caribbean individuals. The interviews explored what the word depression meant to
      participants, and their beliefs regarding depression's causes. RESULTS:
      Depression was often viewed as an illness arising from adverse personal and
      social circumstances that accrue in old age. White British and Black Caribbean
      participants defined depression in terms of low mood and hopelessness; South
      Asian and Black Caribbean participants frequently defined depression in terms of
      worry. Those receiving antidepressants were more likely to acknowledge
      psychological symptoms of depression. Differences in attribution were found
      between the ethnic groups. IMPLICATIONS: A social model of depression is closer
      to the beliefs of older people than the traditional medical model. Culturally
      appropriate inquiries about recent life events could be used to facilitate
      discussion about depression. Our data suggest that many older adults would
      respond to probing by primary care physicians about their mood. Health and social
      care professionals need to be sensitive to the language of depression used by
      different ethnic groups.

PMID- 16452283
TI  - Assessing and comparing physical environments for nursing home residents: using
      new tools for greater research specificity.
AB  - PURPOSE: We developed and tested theoretically derived procedures to observe
      physical environments experienced by nursing home residents at three nested
      levels: their rooms, the nursing unit, and the overall facility. Illustrating
      with selected descriptive results, in this article we discuss the development of
      the approach. DESIGN AND METHODS: On the basis of published literature, existing
      instruments, and expert opinion about environmental elements that might affect
      quality of life, we developed separate observational checklists for the room and
      bath environment, unit environment, and facility environment. We trained 40
      interviewers without specialized design experience to high interrater reliability
      with the room-level assessment. We used the three checklists to assess 1,988
      resident room and bath environments, 131 nursing units, and 40 facilities in five
      states. From the data elements, we developed quantitative indices to describe the
      facilities according to environmentally relevant constructs such as function
      enhancing features, life-enriching features, resident environmental controls, and
      personalization. RESULTS: We reliably gathered data on a large number of
      environmental items at three environmental levels. Environments varied within and
      across facilities, and we noted many environmental deficits potentially relevant
      to resident quality of life. IMPLICATIONS: This research permits resident
      specific data collection on physical environments and resident-level research
      using hierarchical analysis to examine the effects of specific environmental
      constellations. We describe practice and research implications for this approach.

PMID- 16452282
TI  - Differences between newly admitted nursing home residents in rural and nonrural
      areas in a national sample.
AB  - PURPOSE: Previous research in specific locales indicates that individuals
      admitted to rural nursing homes have lower care needs than individuals admitted
      to nursing homes in urban areas, and that rural nursing homes differ in their mix
      of short-stay and chronic-care residents. This research investigates whether
      differences in acuity are a function of differences in resident payer status and
      occur for both individuals admitted for short stays, with Medicare as payer, and
      those needing chronic care. DESIGN AND METHODS: We used a representative 10%
      sample of national resident assessments (Minimum Data Set) for calendar year 2000
      (N = 197,589). We conducted statistical analyses (means, percentages, and
      logistic regression) to investigate differences in Medicare and non-Medicare
      admissions to facilities in metropolitan and nonmetropolitan areas. RESULTS: Non
      Medicare residents admitted to rural nursing facilities have lower acuity scores
      than non-Medicare residents admitted to metropolitan nursing homes. However,
      individuals admitted under Medicare were similar in rural and urban areas.
      IMPLICATIONS: Differences in resident acuity at admission among facilities in
      different locales were largely a function of lower acuity levels for individuals
      admitted to rural nursing homes for long-term or chronic care, although
      differences in Medicare census also played some role in facility-level
      differences in acuity. Other factors must be explored to determine why this lower
      acuity occurs and whether higher use of rural nursing homes by less impaired
      older persons meets their needs and preferences and represents good public
      policy.

PMID- 16452284
TI  - Caregivers' reasons for nursing home placement: clues for improving discussions
      with families prior to the transition.
AB  - PURPOSE: This study identifies the relative importance of reasons for
      institutionalization endorsed by caregivers of patients with dementia; examines
      the relationship between caregivers' reasons for institutionalization and
      indicators of caregiver and patient physical and emotional functioning measured
      in the prior year; and compares, on these indicators, caregivers who
      institutionalized their care recipients with caregivers who did not. DESIGN AND
      METHODS: Participants were 2,200 caregivers from the National Longitudinal
      Caregiver Study, including 580 who institutionalized their care recipient during
      the 3-year interval. Caregivers' reason(s) for institutionalization were examined
      and correlated with indicators of caregiver and patient physical and emotional
      functioning. These indicators were used in a proportional hazards model to
      determine independent predictors. RESULTS: Caregivers' reasons for placement
      included (a) the need for more skilled care (65%); (b) the caregivers' health
      (49%); (c) the patients' dementia-related behaviors (46%); and (d) the need for
      more assistance (23%). Each of these reasons was significantly associated with
      indicators in the prior year's survey. This study uniquely demonstrates that
      caregiving task demand and a single-item measure of caregiver life satisfaction
      significantly predict placement. IMPLICATIONS: These findings emphasize that
      caregivers' reasons have valid underpinnings and that institutionalization of
      dementia patients results from caregiver and patient factors evident in the year
      prior to placement. In routine office visits, caregivers should be systematically
      screened; accounts of low life satisfaction, dementia problem behaviors, or high
      task demand should cue clinicians that discussions of nursing home placement
      would be timely and appropriate.

PMID- 16452285
TI  - Organizational characteristics associated with staff turnover in nursing homes.
AB  - PURPOSE: The association between certified nurse aide, licensed practical nurse,
      and registered nurse turnover and the organizational characteristics of nursing
      homes are examined. DESIGN AND METHODS: Hypotheses for eight organizational
      characteristics are examined (staffing levels, top management turnover, resident
      case mix, facility quality, ownership, chain membership, size, and Medicaid
      census), using Online Survey, Certification, and Reporting (known as OSCAR) data.
      Turnover information came from primary data collected from 854 facilities in six
      states (Missouri, Texas, Connecticut, New York, Pennsylvania, and New Jersey).
      RESULTS: The 1-year turnover rates were 56.4%, 39.7%, and 35.8% for certified
      nurse aides, licensed practical nurses, and registered nurses, respectively. The
      results consistently show that, for all caregivers, lower staffing levels, lower
      quality, for-profit ownership, and higher bed size are associated with higher
      turnover. Some differences also are found for different levels of turnover, but
      there are few differences among types of nursing staff. IMPLICATIONS: Given that
      turnover rates are problematic, this study gives us a better understanding of the
      phenomenon and at the same time helps us further understand the wide variation
      that is known to exist between nursing homes, based on their organizational
      characteristics.

PMID- 16452286
TI  - Nursing home staffing standards: their relationship to nurse staffing levels.
AB  - PURPOSE: This study reviews staffing standards from the 50 states and the
      District of Columbia to determine if these standards are related to nursing home
      staffing levels. DESIGN AND METHODS: Rules and regulations for states' nursing
      home staffing standards were obtained for the 50 states and the District of
      Columbia. Nurse staffing data were obtained from the Centers for Medicare and
      Medicaid Services On-Line Survey, Certification, and Reporting (known as OSCAR)
      database. The minimum hours per resident day (HPRD) staffing standards for each
      state were categorized according to the following: no state-specific HPRD
      standard (adheres only to federal staffing guidelines); low HPRD standard (< or =
      2.5 HPRD); and high HPRD standard (> 2.5 HPRD). A series of hierarchical linear
      models examined the relationships between state staffing standards and actual
      facility staffing (total, licensed, and certified nurse aide HPRD), using a
      number of covariates. RESULTS: The variance in facility staffing was much greater
      within than between states. Facilities in states with high staffing standards had
      somewhat higher staffing than states with no standards or low standards, whereas
      facility staffing in states with low standards was not significantly different
      from that in states with no standards. Other factors, such as resident acuity and
      average state Medicaid rate, also were related to staffing. IMPLICATIONS: State
      staffing standards may not be effective policy tools because they are only one of
      many factors that affect facility staffing levels. Setting a low minimum HPRD
      standard may fail to raise staffing, or it may even have a dampening effect on
      staffing rates in facilities.

PMID- 16452287
TI  - Obtaining self-report data from cognitively impaired elders: methodological
      issues and clinical implications for nursing home pain assessment.
AB  - PURPOSE: We developed and evaluated an explicit procedure for obtaining self
      report pain data from nursing home residents across a broad range of cognitive
      status, and we evaluated the consistency, stability, and concurrent validity of
      resident responses. DESIGN AND METHODS: Using a modification of the Geriatric
      Pain Measure (GPM-M2), we interviewed 61 residents from two nursing homes (Mini
      Mental State Examination score, M = 15 +/- 7) once a week for 4 consecutive
      weeks. We collected additional data by means of chart review, cognitive status
      assessments, and surveys of certified nursing assistants. We used descriptive and
      correlational analyses to address our primary aims. RESULTS: Eighty-nine percent
      of residents completed all four scheduled interviews. Cognitive status was not
      significantly correlated with number of nonresponses and prompts for yes-no
      questions, but it was significantly correlated with nonresponses and prompts for
      Likert-scale questions (r = -.48, p <.001 and r = -.59, p <.001, respectively).
      Completion time for the 17-item pain measure (M = 13 min) was not predicted by
      cognitive status. Residents' scores on the GPM-M2 were significantly correlated
      with number of chronic pain-associated diagnoses, r =.37, p <.01, and internal
      consistency was excellent, alpha = 0.87 - 0.91. Residents' GPM-M2 scores were
      stable over time, r =.74-.80, p <.0001, for all comparisons. IMPLICATIONS: Using
      explicit protocols and reporting procedural data allows researchers and
      clinicians to better understand and apply results of self-report studies with
      cognitively impaired elders. Results suggest that many nursing home residents can
      provide consistent and reliable self-report pain data, given appropriate time and
      assistance.

PMID- 16452288
TI  - Dressing of cognitively impaired nursing home residents: description and
      analysis.
AB  - PURPOSE: Getting dressed is an activity that is of particular difficulty for many
      persons with dementia, given the need for hand-eye coordination, fine motor
      skills, and overall planning skills. Despite several studies concerning
      interventions to improve dressing behavior, very little is known about the
      dressing process as it is currently performed. The purpose of this study is to
      characterize the dressing activity of daily living (ADL) of nursing home
      residents suffering from dementia and thereby identify ways to improve the
      dressing process. DESIGN AND METHODS: We analyzed videotapes of dressing of 20
      special care unit residents to describe the dressing process and the interaction
      between residents and staff members. RESULTS: Staff members completely dressed
      the residents in the majority of cases. Interaction between the staff members and
      the residents was considered insufficient in most sessions. IMPLICATIONS: The
      study identified possible intervention techniques, assistive devices,
      organizational routines, and environmental changes that may improve the dressing
      process. The results have implications that nursing homes may consider in their
      policies, care activities, staff training, and environment to facilitate safety,
      comfort, and satisfaction during the dressing process.

PMID- 16452289
TI  - The role of family functioning in the stress process of dementia caregivers: a
      structural family framework.
AB  - PURPOSE: The purpose of the study was to evaluate the role of family functioning
      in the stress process in a sample of caregivers of dementia patients by using a
      structural family framework. The stress-process model of caregiver distress
      included family functioning as an intervening variable in the relationship
      between objective burden and distress. We theorized family functioning to
      partially mediate the relationship between objective burden and distress and to
      significantly account for the prediction of distress beyond well-recognized
      predictors. DESIGN AND METHODS: One hundred eighty-one family caregivers from the
      Miami site of the Resources for Enhancing Alzheimer's Caregiver Health project
      participated in this study. We assessed sociodemographics, burden, depression,
      anxiety, and perceived health for each caregiver. We measured family functioning
      by using a multidimensional and observational instrument. We used structural
      equation modeling to assess the fit of the model for the overall sample and for
      different caregiver subgroups and to examine whether demographic variables
      affected the relationships in the model. RESULTS: The results of the study
      indicated that family functioning significantly contributed to distress in the
      overall sample and partially mediated the relationship between objective burden
      and distress. We also found that the stress-process model was adequately fit by
      the hypothesized relationships between objective burden, family functioning, and
      distress for the overall sample and all of the subsamples, except for wives.
      IMPLICATIONS: This study provides support for the structural family approach as
      an explanatory model for the influence of family functioning on dementia
      caregivers. Family structural functioning is one contributor to the caregiver
      stress process. This suggests that interventions targeting structural family
      problems may reduce caregiver distress.

PMID- 16452290
TI  - At the eleventh hour: psychosocial dynamics in short hospice stays.
AB  - PURPOSE: This study explored the psychosocial dynamics of short hospice stays
      (less than 2 weeks) of cancer patients age 65 and older. DESIGN AND METHODS: In
      depth interviews with 59 caregivers of 50 patients were audiotaped, transcribed,
      and coded by using Atlas ti software. RESULTS: A descriptive typology is
      presented. A late diagnosis (n = 22 or 44%) was one in which cancer was diagnosed
      between 2 and 4 weeks before death, rendering earlier hospice admission
      impossible. Late diagnoses were made because the cancer was missed, masked by
      comorbidities, or the person resisted seeing a health care provider. A known
      diagnosis (n = 25 or 50%) was one in which the diagnosis was made long before
      hospice admission; admission was delayed because the person elected ongoing
      curative treatment until the final days of life, or the family managed the care
      without hospice until a turning point (medical, functional, pragmatic, or
      emotional) occurred, making the care unmanageable. IMPLICATIONS: Hospice
      utilization is influenced by the interrelationship among patient-family-provider
      factors. Understanding the characteristics and needs of subgroups of terminally
      ill people is key to providing good care at life's end.

PMID- 16452291
TI  - Promoting independence for wheelchair users: the role of home accommodations.
AB  - PURPOSE: The objective of this research is to investigate whether home
      accommodations influence the amount of human help provided to a nationally
      representative sample of adults who use wheelchairs. DESIGN AND METHODS: We
      analyzed data from the Adult Disability Follow-back Survey (DFS), Phase II, of
      the Disability Supplement to the 1994-1995 National Health Interview Surveys
      (NHIS-D). The analytic sample consisted of 899 adults aged 18 and older who
      reported using wheelchairs in the previous 2 weeks. We conducted logistic
      regression and ordinary least squares (OLS) regression analyses to test the
      influence of home accommodations on the receipt of any human help, and among
      respondents who received help, on the hours of help received, respectively. We
      analyzed paid and unpaid help separately. RESULTS: Home accommodations were
      related to the receipt of unpaid, but not paid, help. Relative to having no home
      accommodations, the presence of each additional accommodation decreased the odds
      of having unpaid help by 14% (OR =.86; 95% CI =.76,.97). Additionally, we
      observed an inverse relationship between the number of accommodations in the home
      and hours of unpaid help (p <.01). For wheelchair users who live alone, specific
      types of home accommodations were also inversely related to hours of unpaid help.
      IMPLICATIONS: Policies that reimburse for home accommodations may be an efficient
      response to the growing demand for home-care support while enabling greater
      autonomy and independence for people who use wheelchairs.

PMID- 16452292
TI  - Trends in the use of assistive technology and personal care for late-life
      disability, 1992-2001.
AB  - We describe national trends during the 1990s in late-life difficulty and
      assistance with self-care activities. Among older Americans living in the
      community and experiencing difficulty with self-care activities, assistive
      technology use increased substantially whereas use of personal care declined.
      Using a decomposition technique, we demonstrate that these shifts in assistance
      toward technology account for half the decline in the number of people dependent
      on personal care.

PMID- 16452293
TI  - Interdisciplinary care planning and the written care plan in nursing homes: a
      critical review.
AB  - PURPOSE: This article is a critical review the history, research evidence, and
      state-of-the-art technology in interdisciplinary care planning and the written
      plan of care in American nursing homes. DESIGN AND METHODS: We reviewed
      educational and empirical literature. RESULTS: Interdisciplinary care planning
      and the written care plan are mandated processes that are imbedded in the
      regulatory fabric and routines of the American nursing home. These processes
      evolved from the discipline of nursing, where care planning has had a long and
      controversial history. IMPLICATIONS: Practice implications are provided.

PMID- 16452294
TI  - The value of telephone support groups among ethnically diverse caregivers of
      persons with dementia.
AB  - PURPOSE: Dementia caregiving is a rapidly growing public health problem.
      Logistical problems prevent many caregivers from utilizing available
      interventions. This article provides a demonstration of the usefulness of
      technology for conducting telephone-based support groups in ethnically diverse
      dementia caregivers. DESIGN AND METHODS: Participants were 41 White American and
      Cuban American dementia caregivers participating at the Miami site of the
      Resources for Enhancing Alzheimer's Caregiver Health (known as REACH) program.
      Support groups were conducted over the telephone in English and Spanish as
      appropriate. RESULTS: Eighty-one percent of the participants found the group
      "valuable," largely because of the social and emotional support and useful
      information obtained from other group members. The majority of caregivers also
      reported that their participation had increased their knowledge and skills as
      caregivers. IMPLICATIONS: The findings demonstrate that telecommunications
      technology can overcome the often formidable logistical problems faced by both
      English- and Spanish-speaking caregivers, and it can provide benefits similar to
      those obtained in face-to-face support groups.

PMID- 16452295
TI  - A general method for manipulating DNA sequences from any organism with optical
      tweezers.
AB  - Mechanical manipulation of single DNA molecules can provide novel information
      about DNA properties and protein-DNA interactions. Here we describe and
      characterize a useful method for manipulating desired DNA sequences from any
      organism with optical tweezers. Molecules are produced from either genomic or
      cloned DNA by PCR using labeled primers and are tethered between two optically
      trapped microspheres. We demonstrate that human, insect, plant, bacterial and
      viral sequences ranging from approximately 10 to 40 kilobasepairs can be
      manipulated. Force-extension measurements show that these constructs exhibit
      uniform elastic properties in accord with the expected contour lengths for the
      targeted sequences. Detailed protocols for preparing and manipulating these
      molecules are presented, and tethering efficiency is characterized as a function
      of DNA concentration, ionic strength and pH. Attachment strength is characterized
      by measuring the unbinding time as a function of applied force. An alternative
      stronger attachment method using an amino-carboxyl linkage, which allows for
      reliable DNA overstretching, is also described.

PMID- 16452296
TI  - Degradation of RNA in bacteria: comparison of mRNA and stable RNA.
AB  - Degradation of RNA plays a central role in RNA metabolism. In recent years, our
      knowledge of the mechanisms of RNA degradation has increased considerably with
      discovery of the participating RNases and analysis of mutants affected in the
      various degradative pathways. Among these processes, mRNA decay and stable RNA
      degradation generally have been considered distinct, and also separate from RNA
      maturation. In this review, each of these processes is described, as it is
      currently understood in bacteria. The picture that emerges is that decay of mRNA
      and degradation of stable RNA share many common features, and that their initial
      steps also overlap with those of RNA maturation. Thus, bacterial cells do not
      contain dedicated machinery for degradation of different classes of RNA or for
      different processes. Rather, only the specificity of the RNase and the
      accessibility of the substrate determine whether or not a particular RNA will be
      acted upon.

PMID- 16452297
TI  - Two conformational states in the crystal structure of the Homo sapiens
      cytoplasmic ribosomal decoding A site.
AB  - The decoding A site of the small ribosomal subunit is an RNA molecular switch,
      which monitors codon-anticodon interactions to guarantee translation fidelity. We
      have solved the crystal structure of an RNA fragment containing two Homo sapiens
      cytoplasmic A sites. Each of the two A sites presents a different conformational
      state. In one state, adenines A1492 and A1493 are fully bulged-out with C1409
      forming a wobble-like pair to A1491. In the second state, adenines A1492 and
      A1493 form non-Watson-Crick pairs with C1409 and G1408, respectively while A1491
      bulges out. The first state of the eukaryotic A site is, thus, basically the same
      as in the bacterial A site with bulging A1492 and A1493. It is the state used for
      recognition of the codon/anticodon complex. On the contrary, the second state of
      the H.sapiens cytoplasmic A site is drastically different from any of those
      observed for the bacterial A site without bulging A1492 and A1493.

PMID- 16452299
TI  - Coordinated changes of histone modifications and HDAC mobilization regulate the
      induction of MHC class II genes by Trichostatin A.
AB  - The deacetylase inhibitor Trichostatin A (TSA) induces the transcription of the
      Major Histocompatibility Class II (MHC II) DRA gene in a way independent of the
      master coactivator CIITA. To analyze the molecular mechanisms by which this
      epigenetic regulator stimulates MHC II expression, we used chromatin
      immunoprecipitation (ChIP) assays to monitor the alterations in histone
      modifications that correlate with DRA transcription after TSA treatment. We found
      that a dramatic increase in promoter linked histone acetylation is followed by an
      increase in Histone H3 lysine 4 methylation and a decrease of lysine 9
      methylation. Fluorescence recovery after photobleaching (FRAP) experiments showed
      that TSA increases the mobility of HDAC while decreasing the mobility of the
      class II enhanceosome factor RFX5. These data, in combination with ChIP
      experiments, indicate that the TSA-mediated induction of DRA transcription
      involves HDAC relocation and enhanceosome stabilization. In order to gain a
      genome-wide view of the genes responding to inhibition of deacetylases, we
      compared the transcriptome of B cells before and after TSA treatment using
      Affymetrix microarrays. This analysis showed that in addition to the DRA gene,
      the entire MHC II family and the adjacent histone cluster that are located in
      chromosome 6p21-22 locus are strongly induced by TSA. A complex pattern of gene
      reprogramming by TSA involves immune recognition, antiviral, apoptotic and
      inflammatory pathways and extends the rationale for using Histone Deacetylase
      Inhibitors (HDACi) to modulate the immune response.

PMID- 16452298
TI  - Post-transcriptional nucleotide modification and alternative folding of RNA.
AB  - Alternative foldings are an inherent property of RNA and a ubiquitous problem in
      scientific investigations. To a living organism, alternative foldings can be a
      blessing or a problem, and so nature has found both, ways to harness this
      property and ways to avoid the drawbacks. A simple and effective method employed
      by nature to avoid unwanted folding is the modulation of conformation space
      through post-transcriptional base modification. Modified nucleotides occur in
      almost all classes of natural RNAs in great chemical diversity. There are about
      100 different base modifications known, which may perform a plethora of
      functions. The presumably most ancient and simple nucleotide modifications, such
      as methylations and uridine isomerization, are able to perform structural tasks
      on the most basic level, namely by blocking or reinforcing single base-pairs or
      even single hydrogen bonds in RNA. In this paper, functional, genomic and
      structural evidence on cases of folding space alteration by post-transcriptional
      modifications in native RNA are reviewed.

PMID- 16452300
TI  - A new anti conformation for N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG)
      allows Watson-Crick pairing in the Sulfolobus solfataricus P2 DNA polymerase IV
      (Dpo4).
AB  - Primer extension studies have shown that the Y-family DNA polymerase IV (Dpo4)
      from Sulfolobus solfataricus P2 can preferentially insert C opposite N
      (deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) [F. Boudsocq, S. Iwai, F.
      Hanaoka and R. Woodgate (2001) Nucleic Acids Res., 29, 4607-4616]. Our goal is to
      elucidate on a structural level how AAF-dG can be harbored in the Dpo4 active
      site opposite an incoming dCTP, using molecular modeling and molecular dynamics
      simulations, since AAF-dG prefers the syn glycosidic torsion. Both anti and syn
      conformations of the templating AAF-dG in a Dpo4 ternary complex were
      investigated. All four dNTPs were studied. We found that an anti glycosidic
      torsion with C1'-exo deoxyribose conformation allows AAF-dG to be Watson-Crick
      hydrogen-bonded with dCTP with modest polymerase perturbation, but other
      nucleotides are more distorting. The AAF is situated in the Dpo4 major groove
      open pocket with fluorenyl rings 3'- and acetyl 5'-directed along the modified
      strand, irrespective of dNTP. With AAF-dG syn, the fluorenyl rings are in the
      small minor groove pocket and the active site region is highly distorted. The
      anti-AAF-dG conformation with C1'-exo sugar pucker can explain the preferential
      incorporation of dC by Dpo4. Possible relevance of our new major groove structure
      for AAF-dG to other polymerases, lesion repair and solution conformations are
      discussed.

PMID- 16452302
TI  - Genetic manipulation of polyamine catabolism in rodents.
AB  - Activation of polyamine catabolism through the overexpression of
      spermidine/spermine N1-acetyltransferase (SSAT) in transgenic rodents does not
      only lead to distorted tissue polyamine homeostasis, manifested as striking
      accumulation of putrescine, appearance N1-acetylspermidine and reduction of
      tissue spermidine and/or spermine pools, but likewise creates striking phenotypic
      changes. The latter include loss of hair, lipoatrophy and female infertility.
      Forced expression of SSAT modulates skin, prostate and intestinal carcinogenesis,
      induces acute pancreatitis and blocks early liver regeneration. Although many of
      these features are directly attributable to altered tissue polyamine pools, some
      of them are more likely related to the greatly accelerated flux of the polyamines
      caused by activated catabolism and compensatorily enhanced biosynthesis.

PMID- 16452301
TI  - Structure of the Tetrahymena thermophila telomerase RNA helix II template
      boundary element.
AB  - Telomere addition by telomerase requires an internal templating sequence located
      in the RNA subunit of telomerase. The correct boundary definition of this
      template sequence is essential for the proper addition of the nucleotide repeats.
      Incorporation of incorrect telomeric repeats onto the ends of chromosomes has
      been shown to induce chromosomal instability in ciliate, yeast and human cells. A
      5' template boundary defining element (TBE) has been identified in human, yeast
      and ciliate telomerase RNAs. Here, we report the solution structure of the TBE
      element (helix II) from Tetrahymena thermophila telomerase RNA. Our results
      indicate that helix II and its capping pentaloop form a well-defined structure
      including unpaired, stacked adenine nucleotides in the stem and an unusual syn
      adenine nucleotide in the loop. A comparison of the T.thermophila helix II
      pentaloop with a pentaloop of the same sequence found in the 23S rRNA of the
      Haloarcula marismortui ribosome suggests possible RNA and/or protein interactions
      for the helix II loop within the Tetrahymena telomerase holoenzyme.

PMID- 16452303
TI  - The post-translational synthesis of a polyamine-derived amino acid, hypusine, in
      the eukaryotic translation initiation factor 5A (eIF5A).
AB  - The eukaryotic translation initiation factor 5A (eIF5A) is the only cellular
      protein that contains the unique polyamine-derived amino acid, hypusine [Nepsilon
      (4-amino-2-hydroxybutyl)lysine]. Hypusine is formed in eIF5A by a novel post
      translational modification reaction that involves two enzymatic steps. In the
      first step, deoxyhypusine synthase catalyzes the cleavage of the polyamine
      spermidine and transfer of its 4-aminobutyl moiety to the epsilon-amino group of
      one specific lysine residue of the eIF5A precursor to form a deoxyhypusine
      intermediate. In the second step, deoxyhypusine hydroxylase converts the
      deoxyhypusine-containing intermediate to the hypusine-containing mature eIF5A.
      The structure and mechanism of deoxyhypusine synthase have been extensively
      characterized. Deoxyhypusine hydroxylase is a HEAT-repeat protein with a
      symmetrical superhelical structure consisting of 8 helical hairpins (HEAT
      motifs). It is a novel metalloenzyme containing tightly bound iron at the active
      sites. Four strictly conserved His-Glu pairs were identified as iron coordination
      sites. The structural fold of deoxyhypusine hydroxylase is entirely different
      from those of the other known protein hydroxylases such as prolyl 4-hydroxylase
      and lysyl hydroxylases. The eIF5A protein and deoxyhypusine/hypusine modification
      are essential for eukaryotic cell proliferation. Thus, hypusine synthesis
      represents the most specific protein modification known to date, and presents a
      novel target for intervention in mammalian cell proliferation.

PMID- 16452304
TI  - The kinase complex responsible for IRF-3-mediated IFN-beta production in myeloid
      dendritic cells (mDC).
AB  - Type I interferons (IFN) IFN-alpha and -beta play a central role in the induction
      of antiviral immunity, which involves up-regulation or activation of a large
      number of IFN-inducible genes in host immune competent cells. Initial events in
      the antiviral response may occur in myeloid dendritic cells (mDCs), and the
      proteins expressed provoke early responses to cope with concomitant infection in
      the host. The participation of transcription factors IRF-3/7, AP1 and NF-kappaB
      in IFN-beta promoter activation in mDCs is well established. An initial trigger
      of this event is a viral dsRNA that is recognized by proteins with an RNA-binding
      motif. Toll-like receptor (TLR) 3 on membranes and RIG-Iin the cytoplasm are
      molecules with dsRNA-recognition ability. Our main aim in the present review is
      to describe how IRF-3 and/or NF-kappaB are activated through the initial
      recognition of dsRNA by these pattern-recognition receptors. By analogy to the
      trimolecular complex of IKKgamma, IKKalpha and IKKbeta, thus far, IRF-3-activated
      kinases have been reported to be kinase complexes with trimolecular assembly. Two
      kinases, TBK1 and IKKepsilon, are thought to be linked to regulatory subunit TANK
      or NAP1 with no kinase activity like IKKgamma. The TLR3 and RIG-I pathways
      converge upstream of IRF-3, possibly at NAP1, the regulatory subunit of IRF-3
      activating kinase. Thus, a novel function of the regulatory subunit has emerged.
      These proteins are involved in the TLR3 and RIG-I pathways, and act as adapters
      bridging on the dsRNA-recognition unit and IRF-3-activating kinases in addition
      to their kinase-regulatory function. Here, we summarize the properties of
      regulatory subunits NAP1 and TANK, and the mode of activation of NF-kappaB and
      IRF-3 in conjunction with the unique properties of the TLR3 function.

PMID- 16452305
TI  - Mammalian chromatin remodeling complex SWI/SNF is essential for enhanced
      expression of the albumin gene during liver development.
AB  - The chromatin remodeling complex SWI/SNF is known to regulate the transcription
      of several genes by controlling chromatin structure in an ATP-dependent manner.
      SWI/SNF contains the Swi2p/Snf2p like ATPases BRG1 or BRM exclusively. We found
      that the expression of BRM gradually increases and that of BRG1 decreases as
      liver cells differentiate. Chromatin immunoprecipitation assays revealed that the
      ATPase subunits of SWI/SNF and tumor suppressor retinoblastoma (RB) family
      proteins bind to the promoter region of the albumin gene in hepatocytes, and that
      the replacement of BRG1 with BRM and pRB with p130 at this site occurs over the
      course of differentiation. Small interfering RNA experiments showed that blocking
      the expression of BRG1 and BRM in fetal and adult hepatocytes, respectively,
      causes a reduction in albumin expression. In luciferase reporter assays with a
      pREP4-based reporter plasmid that forms a chromatin structure, BRG1 showed
      activity stimulating the expression of the albumin promoter mediated by
      CCAAT/enhancer-binding protein alpha (C/EBPalpha). This enhancement was
      facilitated by the RB family members pRB and p130. ATPase assays showed that both
      pRB and C/EBPalpha proteins directly stimulate the ATPase activity of BRG1. Our
      findings suggest that the mechanism by which the activity of transcription
      factors is enhanced by RB family members and SWI/SNF includes an increase in the
      ATPase activity of the chromatin remodeling complex.

PMID- 16452306
TI  - Prodomain processing of recombinant plasmepsin II and IV, the aspartic proteases
      of Plasmodium falciparum, is auto- and trans-catalytic.
AB  - Prodomain processing of the four food vacuole plasmepsins (PMs), the malarial
      aspartic proteases, is prerequisite for their activity on hemoglobin degradation
      of the parasite Plasmodium falciparum. Although previous studies have suggested
      the involvement of a calpain-like PM convertase in the processing of PMs, the
      underlying mechanism of their processing remains to be clarified. Here, to
      investigate the mechanism by which food vacuole PM II and IV are processed, we
      used their wild-type and mutant proteins in which the catalytic Asp residue in
      two active-site motifs was mutated, as well as protease inhibitors. Autocatalytic
      processing of wild-type PM II and IV was inhibited only by an aspartic protease
      inhibitor pepstatin A. Unexpectedly, their proteolytic activities were inhibited
      not only by pepstatin A but also by calpain inhibitor ALLN. The active-site
      mutants of both PM II and IV showed neither autocatalytic processing nor
      proteolytic activities. However, the mutants of both PMs were efficiently
      processed upon incubation with their respective wild type proteins. Furthermore,
      the mutants of both PMs were processed upon incubation with each other's wild
      type PM in both pepstatin A- and ALLN-sensitive manners. These results suggest
      that the processing of PM II and IV occurs via an intra- and inter-molecular
      autocatalytic event as well as via a transcatalytic event between them.

PMID- 16452307
TI  - Paenidase, a novel D-aspartyl endopeptidase from Paenibacillus sp. B38:
      purification and substrate specificity.
AB  - We discovered and characterized a novel type D-aspartyl endopeptidase (DAEP)
      produced extracellularly by Paenibacillus sp. B38. This bacterial DAEP of M(r)
      34,798 (named paenidase) appeared to be converted into a smaller form of M(r)
      34,169 by the proteolytic removal of 5 amino acid residues from the N-terminal.
      The intact and modified forms of the enzyme displayed essentially the same
      enzymatic properties. The enzyme specifically hydrolyzed succinyl-D-aspartic acid
      alpha-(p-nitroanilide) and succinyl-D-aspartic acid alpha-(4-methylcoumaryl-7
      amide) to generate p-nitroaniline and 7-amino-4-methylcoumarin, and internally
      cleaved a synthetic peptide (D-A-E-F-R-H-[D-Asp]-G-S-Y) of the [D-Asp](7) amyloid
      beta (Abeta) protein between [D-Asp](7)-G(8). Either was totally inert to the
      normal Abeta peptide sequence containing L-Asp, instead of D-Asp at the 7th
      position. Thus, paenidase is the first DAEP from a microorganism that
      specifically recognizes an internal D-Asp residue to cleave [D-Asp]-X peptide
      bonds.

PMID- 16452308
TI  - Superoxide stress decreases expression of srfA through inhibition of
      transcription of the comQXP quorum-sensing locus in Bacillus subtilis.
AB  - During the course of screening for competence-deficient mutants in the mutant
      collection constructed by the Japan Consortium of Bacillus Functional Genomics, a
      disruption mutant of sodA encoding superoxide dismutase was identified as a
      mutant with decreased transformation efficiency. In fact, in the sodA mutant we
      observed a severe decrease in the expression of srfA required for the development
      of genetic competence. Northern and primer extension analyses revealed inhibition
      of the transcription of the comQXP quorum-sensing locus in the sodA mutant,
      thereby preventing srfA expression. Furthermore, an excess amount of superoxide
      anion induced by the addition of paraquat also resulted in a decrease in comQXP
      transcription. Thus, it was concluded that high levels of superoxide are able to
      inhibit specifically the transcription of the comQXP operon. In support of this
      conclusion, the effect of added paraquat was significantly alleviated in a comX
      independent srfA expression system.

PMID- 16452309
TI  - Binding of glucose to the D-galactose/D-glucose-binding protein from Escherichia
      coli restores the native protein secondary structure and thermostability that are
      lost upon calcium depletion.
AB  - The effect of the depletion of calcium on the structure and thermal stability of
      the D-galactose/D-glucose-binding protein (GGBP) from Escherichia coli was
      studied by fluorescence spectroscopy and Fourier-transform infrared spectroscopy.
      The calcium-depleted protein (GGBP-Ca) was also studied in the presence of
      glucose (GGBP-Ca/Glc). The results show that calcium depletion has a small effect
      on the secondary structure of GGBP, and, in particular it affects a population of
      alpha-helices with a low exposure to solvent. Alternatively, glucose-binding to
      GGBP-Ca eliminates the effect induced by calcium depletion by restoring a
      secondary structure similar to that of the native protein. In addition, the
      infrared and fluorescence data obtained reveal that calcium depletion markedly
      reduces the thermal stability of GGBP. In particular, the spectroscopic
      experiments show that the depletion of calcium mainly affects the stability of
      the C-terminal domain of the protein. However, the binding of glucose restores
      the thermal stability of GGBP-Ca. The thermostability of GGBP and GGBP-Ca was
      also studied by molecular dynamics simulations. The simulation data support the
      spectroscopic results. New insights into the role of calcium in the thermal
      stability of GGBP contribute to a better understanding of the protein function
      and constitute important information for the development of biotechnological
      applications of this protein. Mutations and/or labelling of amino acid residues
      located in the protein C-terminal domain may affect the stability of the whole
      protein structure.

PMID- 16452310
TI  - A novel 96-kDa aminopeptidase localized on epithelial cell membranes of Bombyx
      mori midgut, which binds to Cry1Ac toxin of Bacillus thuringiensis.
AB  - Proteins in the brush border membrane (BBM) of the midgut binding to the
      insecticidal Cry1Ac toxin from Bacillus thuringiensis were investigated to
      examine the lower sensitivity of Bombyx mori to Cry1Ac, and new aminopeptidase N
      that bound to Cry1Ac was discovered. DEAE chromatography of Triton X-100-soluble
      BBM proteins from the midgut revealed 96-kDa aminopeptidase that bound to Cry1Ac.
      The enzyme was purified to homogeneity and estimated to be a 96.4-kDa molecule on
      a silver-stained SDS-PAGE gel. However, the native protein was eluted as a single
      peak corresponding to approximately 190-kDa on gel filtration and gave a single
      band on native PAGE. The enzyme was determined to be an aminopeptidase N (APN96)
      from its substrate specificity. Antiserum to class 3 B. mori APN (BmAPN3)
      recognized APN96, but peptide mass fingerprinting revealed that 54% of the amino
      acids of matched peptides were identical to those of BmAPN3, suggesting that
      APN96 was a novel isoform of the APN3 family. On ligand blots, APN96 bound to
      Cry1Ac but not Cry1Aa or Cry1Ab, and the interaction was inhibited by GalNAc.
      K(D) of the APN96-Cry1Ac interaction was determined to be 1.83 +/- 0.95 microM.
      The lectin binding assay suggested that APN96 had an N-linked bi-antennal
      oligosaccharide or an O-linked mucin type one. The role of APN96 was discussed in
      relation to the insensitivity of B. mori to Cry1Ac.

PMID- 16452311
TI  - Cloning and expression of the pyridoxal 5'-phosphate-dependent aspartate racemase
      gene from the bivalve mollusk Scapharca broughtonii and characterization of the
      recombinant enzyme.
AB  - D-aspartate is present at high concentrations in the tissues of Scapharca
      broughtonii, and its production depends on aspartate racemase. This enzyme is the
      first aspartate racemase purified from animal tissues and unique in its pyridoxal
      5'-phosphate (PLP)-dependence in contrast to microbial aspartate racemases thus
      far characterized. The enzyme activity is markedly increased in the presence of
      AMP and decreased in the presence of ATP. To analyze the structure-function
      relationship of the enzyme further, we cloned the cDNA of aspartate racemase, and
      then purified and characterized the recombinant enzyme expressed in Escherichia
      coli. The cDNA included an open reading frame of 1,017 bp encoding a protein of
      338 amino acids, and the deduced amino acid sequence contained a PLP-binding
      motif. The sequence exhibits the highest identity (43-44%) to mammalian serine
      racemase, followed mainly by threonine dehydratase. These relationships are fully
      supported by phylogenetic analyses of the enzymes. The active recombinant
      aspartate racemase found in the Escherichia coli extract represented about 10% of
      total bacterial protein and was purified to display essentially identical
      physicochemical and catalytic properties with those of the native enzyme. In
      addition, the enzyme showed a dehydratase activity toward L-threo-3
      hydroxyaspartate, similar to the mammalian serine racemase that produces pyruvate
      from D- and L-serine.

PMID- 16452313
TI  - Apoptosis occurs via the ceramide recycling pathway in human HaCaT keratinocytes.
AB  - Keratinocytes contain abundant ceramides compared to other cells. However,
      studies on these cells have mainly focused on the barrier function of ceramide,
      while their other roles, such as those in apoptosis or cell cycle arrest, have
      not been well addressed. In this study, we investigated the apoptosis-inducing
      effect of exogenously added cell-permeable ceramides in HaCaT keratinocytes. We
      found that N-hexanoyl sphingosine (C6-ceramide) induced apoptosis efficiently
      through the accumulation of long chain ceramides. On the other hand, N-acetyl
      sphingosine (C2-ceramide) induced neither apoptosis nor accumulation of long
      chain ceramides. We also found that exogenously added C6-ceramide was hydrolyzed
      to sphingosine and then reacylated in long chain ceramides (ceramide recycling
      pathway), but that C2-ceramide was not hydrolyzed and thus not recycled. We
      propose that this is the basis for the chain length-specific heterogeneity
      observed in ceramide-induced apoptosis in these cells. These results also imply
      that keratinocytes utilize exogenous sphingolipids or ceramides to coordinate
      their own ceramide compositions.

PMID- 16452312
TI  - The internalization and metabolism of 3-deoxyglucosone in human umbilical vein
      endothelial cells.
AB  - 3-Deoxyglucosone (3-DG), a dicarbonyl compound produced by glycation, plays a
      role in the modification and cross-linking of long-lived proteins. We synthesized
      [3H]3-DG from [3H]glucose and developed an internalization assay system using
      HPLC to examine its cellular metabolism. When smooth muscle cells or human
      umbilical vein endothelial cells were incubated with [3H]3-DG, it was found that
      [3H]3-DG was internalized by cells in a time dependent manner. The rate of
      internalization was reduced when the cells were incubated at 4 degrees C or
      treated with phenylarsine oxide (PAO). By monitoring [3H]3-DG taken up by cells,
      it was confirmed that 3-DG is reduced to 3-deoxyfructose (3-DF) and that this
      reaction was inhibited by an aldo-keto reductase inhibitor (ARI). The presence of
      3-DG led to an increase in reactive oxygen species levels in the cells and
      subsequent apoptosis, and the effect was enhanced by pretreatment with ARI. These
      results suggest that 3-DG is internalized by cells and reduced to 3-DF by aldo
      keto reductases, and that the internalized 3-DG is responsible for the production
      of intracellular oxidative stress.

PMID- 16452315
TI  - The effects of the side chains of hydrophobic aliphatic amino acid residues in an
      amphipathic polypeptide on the formation of alpha helix and its association.
AB  - The polypeptide alpha3, which was synthesized by us to produce an amphipathic
      helix structure, contains the regular three times repeated sequence (LETLAKA)(3),
      and alpha3 forms a fibrous assembly. To clarify how the side chains of amino acid
      residues affect the formation of alpha helix, Leu residues, which are located in
      the hydrophobic surface of an amphipathic helix, were replaced by other
      hydrophobic aliphatic amino acid residues systematically, and the characters of
      the resulting polypeptides were studied. According to the circular dichroism (CD)
      spectra, the Ile-substituted polypeptides formed alpha helix like alpha3.
      However, their helix formation ability was weaker than that of alpha3 under some
      conditions. The Val-substituted polypeptides formed alpha helix only under
      restricted condition. The Ala-substituted polypeptides did not form alpha helix
      under any condition. Thus, it is clear that the order of the alpha helix
      formation ability is as follows: Leu >or= Ile > Val > Ala. The formation of alpha
      helix was confirmed by Fourier Transform Infrared (FTIR) spectra. Through
      electron microscopic observation, it was clarified that the formation of the
      alpha helix structure correlates with the formation of a fibrous assembly. The
      amphipathic alpha helix structure would be stabilized by the formation of the
      fibrous assembly.

PMID- 16452314
TI  - Attenuation of cardiac hypertrophy in carnitine-deficient juvenile visceral
      steatosis (JVS) mice achieved by lowering dietary lipid.
AB  - We examined the development of cardiac hypertrophy in juvenile visceral steatosis
      (JVS) mice, a model of systemic carnitine deficiency, by varying the amount of
      lipid in the diet. Cardiac hypertrophy was markedly attenuated by decreasing soy
      bean oil (SBO) from 5% (w/w) to 1%. Triglyceride contents of the ventricles of
      JVS mice fed 1% SBO were significantly lower than in JVS mice fed 5% SBO. The
      addition of medium-chain triglycerides metabolically utilized by JVS mice did not
      affect the development of cardiac hypertrophy. On the other hand, the mRNA levels
      of atrial natriuretic peptide and skeletal alpha-actin, which are related to
      cardiac hypertrophy, were also attenuated by decreasing lipid in the diet.
      Adenylate energy charge and creatine phosphate in the heart of JVS mice at the
      early stage of hypertrophy were not significantly different from control mice
      given the same laboratory chow (4.6% of lipid). Although urinary prostaglandin
      F(2alpha) levels were found to be increased in JVS mice at 15 days of age when
      they developed cardiac hypertrophy, administration of aspirin was not
      efficacious. We, therefore, propose that the proportion of lipid in the diet is
      important in the development of cardiac hypertrophy in carnitine-deficient JVS
      mice, and that this is not related to prostaglandin formation.

PMID- 16452316
TI  - Analysis of sialyltransferase-like proteins from Oryza sativa.
AB  - Sialic acids are widely distributed among living creatures, from bacteria to
      mammals, but it has been commonly accepted that they do not exist in plants.
      However, with the progress of genome analyses, putative gene homologs of animal
      sialyltransferases have been detected in the genome of some plants. In this
      study, we cloned three genes from Oryza sativa (Japanese rice) that encode
      sialyltransferase-like proteins, designated OsSTLP1, 2, and 3, and analyzed the
      enzymatic activity of the proteins. OsSTLP1, 2, and 3 consist of 393, 396, and
      384 amino acids, respectively, and each contains sequences similar to the sialyl
      motifs that are highly conserved among animal sialyltransferases. The recombinant
      soluble forms of OsSTLPs produced by COS-7 cells were analyzed for
      sialyltransferase-like activity. OsSTLP1 exhibited such activity toward the
      oligosaccharide Galbeta1,4GlcNAc and such glycoproteins as asialofetuin, alpha1
      acid glycoprotein, and asialo-alpha1-acid glycoprotein; OsSTLP3 exhibited similar
      activity toward asialofetuin; and OsSTLP2 exhibited no sialyltransferase-like
      activity. The sialic acid transferred by OsSTLP1 or 3 was linked to galactose of
      Galbeta1,4GlcNAc through alpha2,6-linkage. This is the first report of plant
      proteins having sialyltransferase-like activity.

PMID- 16452317
TI  - Troponin is a potential regulator for actomyosin interactions.
AB  - Troponin extracted from rabbit skeletal muscle directly binds to an actin
      filament in a molar ratio of 1:1 even in the absence of tropomyosin. An actin
      filament decorated with troponin did not exhibit significant difference from pure
      actin filaments in the maximum rate of actomyosin ATP hydrolysis and the sliding
      velocity of the filament examined by means of an in vitro motility assay.
      However, the relative number of troponin-bound actin filaments moving in the
      absence of calcium ions decreased to half that in their presence. The amount of
      HMM bound to the filaments was less than 4% of actin monomers in the presence of
      TNs. In addition, actin filaments could not move when Tn molecules were bound in
      the molar ratio of about 1:1 although they sufficiently bind to myosin heads.
      These results indicate that troponin can transform an actin monomer within a
      filament into an Off-state without sterically blocking of the myosin-binding
      sites with tropomyosin molecules.

PMID- 16452318
TI  - Potential role for astroglial D-amino acid oxidase in extracellular D-serine
      metabolism and cytotoxicity.
AB  - D-amino acid oxidase (DAO) is a flavoenzyme that catalyzes the oxidation of D
      amino acids. In the brain, gene expression of DAO is detected in astrocytes.
      Among the possible substrates of DAO in vivo, D-serine is proposed to be a
      neuromodulator of the N-methyl-D-aspartate (NMDA) receptor. In a search for the
      physiological role of DAO in the brain, we investigated the metabolism of
      extracellular D-serine in glial cells. Here we show that after D-serine
      treatment, rat primary type-1 astrocytes exhibited increased cell death. In order
      to enhance the enzyme activity of DAO in cells, we established stable rat C6
      glial cells overexpressing mouse DAO designated as C6/DAO. Treatment with a high
      dose of D-serine led to the production of hydrogen peroxide (H(2)O(2)) followed
      by apoptosis in C6/DAO cells. Among the amino acids tested, D-serine specifically
      exhibited a significant cell death-inducing effect. DAO inhibitors, i.e., sodium
      benzoate and chlorpromazine, partially prevented the death of C6/DAO cells
      treated with D-serine, indicating the involvement of DAO activity in d-serine
      metabolism. Overall, we consider that extracellular D-serine can gain access to
      intracellular DAO, being metabolized to produce H(2)O(2). These results support
      the proposal that astroglial DAO plays an important role in metabolizing a
      neuromodulator, D-serine.

PMID- 16452319
TI  - Suppression of STAT3 activity by Duplin, which is a negative regulator of the Wnt
      signal.
AB  - Duplin was originally isolated as a negative regulator of beta-catenin-dependent
      T-cell factor (Tcf) transcriptional activity in the Wnt signaling pathway.
      However, Duplin knockout mice exhibit embryonic lethality at 5.5-em day,
      suggesting that Duplin has important roles other than as a negative regulator of
      the Wnt signal. To identify new roles of Duplin, the Duplin-binding proteins were
      screened. PIAS3, which is a SUMO E3 ligase and acts as an inhibitor of signal
      transducer and activator of transcription (STAT3), was identified as a Duplin
      binding protein. Duplin was sumoylated, but PIAS3 affected neither the
      sumoylation of Duplin nor its ability to inhibit Tcf-4 activity. Like PIAS3,
      Duplin suppressed the leukemia-inhibitory factor (LIF)-induced STAT3
      transcriptional activity. Duplin did not affect the LIF-dependent tyrosine
      phosphorylation or nuclear localization of STAT3 but inhibited the formation of
      complex between STAT3 and DNA. Although STAT3 is not modified with SUMO, PIAS3
      inhibited the STAT3 activity in a manner partially depending on its SUMO E3
      ligase activity. Duplin suppressed the LIF-dependent STAT3 activity independently
      of sumoylation. These results demonstrate that Duplin inhibits not only Tcf-4 but
      also STAT3, suggesting that Duplin may act as a repressor for multiple
      transcriptional factors.

PMID- 16452320
TI  - Endemic iron deficiency associated with Helicobacter pylori infection among
      school-aged children in Alaska.
AB  - OBJECTIVES: Rural Alaska Natives have a high prevalence of iron deficiency and
      Helicobacter pylori infection. The objective of this study was to estimate the
      prevalence of iron deficiency, iron-deficiency anemia, and active H pylori
      infection among school-aged children in rural Alaska. METHODS: We enrolled 68%
      (688) of the 7- to 11-year-old children from 10 predominantly Alaska Native
      villages in southwestern Alaska. We collected venous blood samples to assess iron
      deficiency and anemia. Each child was tested for active H pylori infection by 13C
      urea breath test (UBT). Evaluated risk factors included age, gender, village of
      residence, number of household members, number of household members who were
      younger than 5 years, recent antibiotic use, and household water source. RESULTS:
      Of 688 enrolled children, iron deficiency was present in 38%, iron-deficiency
      anemia was present in 7.8%, and H pylori infection by UBT was present in 86%.
      Iron deficiency was independently associated with living in a household with >6
      people and village of residence. H pylori infection by UBT was independently
      associated with child's age > or =10 years and village of residence. Ninety-one
      percent of children with iron deficiency had H pylori infection by UBT, and
      children with active H pylori infection were more likely to be iron deficient
      than uninfected children. Children with H pylori infection by UBT were also more
      likely to have iron-deficiency anemia than uninfected children. CONCLUSIONS: In
      this study of nearly 700 children in 10 different villages in Alaska, we
      confirmed that the high prevalence of iron deficiency persists among school-aged
      children. We found that active H pylori infection was independently associated
      with iron deficiency and iron-deficiency anemia among children in this region. H
      pylori infection may account for a portion of the iron deficiency and iron
      deficiency anemia in rural Alaska and other areas with high prevalences of both
      conditions. Innovative approaches are critically needed to address the iron
      deficiency in high prevalence areas such as rural Alaska and most of the
      developing world.

PMID- 16452321
TI  - Sarcoidosis in chronic granulomatous disease.
AB  - In addition to increased susceptibility to infections in patients with chronic
      granulomatous disease (CGD), a higher incidence of sterile inflammatory disorders
      in these patients has been noted. However, sarcoidosis has not been reported
      previously in CGD. In this report, we describe two patients who have CGD and a
      disorder consistent with sarcoidosis on the basis of unequivocal clinical
      radiographic presentations, their responses to treatment, and serum angiotensin
      converting enzyme levels. Serum angiotensin-converting enzyme levels were
      measured in 26 other patients with CGD to establish an appropriate reference
      range. A possible relationship between CGD and sarcoidosis is discussed.

PMID- 16452322
TI  - Prenatal diagnosis of familial type I choledochal cyst.
AB  - Familial choledochal cysts are extremely rare. High-resolution ultrasound now
      allows for the antenatal diagnosis of these anomalies. After delivery, elective
      surgical resection should be planned; however, increases in size, deterioration
      of liver function, and ascending cholangitis frequently force early intervention.
      We report an unusual occurrence of siblings with type I choledochal cysts and
      review the existing literature on cause, genetics, classification, diagnosis, and
      management of this disease.

PMID- 16452323
TI  - Body-checking rules and childhood injuries in ice hockey.
AB  - BACKGROUND: Body checking is the predominant mechanism of youth ice hockey
      injuries. The Canadian Hockey Association has allowed body checking from ages 12
      to 13 (peewee level) and up. One Canadian province (Ontario) introduced body
      checking at ages 10 to 11 (atom level) in the competitive leagues, whereas in
      Quebec body checking has only been allowed at ages 14 to 15 (bantam Level). The
      purpose of this study was to compare body-checking injuries, fractures, and
      concussions in boys' minor hockey between jurisdictions in which checking is
      allowed and jurisdictions in which body checking is not allowed. METHODS: Data
      from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) were
      used to characterize children's ice hockey injuries from September 1995 to the
      end of August 2002. Children treated at CHIRPP hospitals in areas in which
      checking was allowed were compared with children in areas in which checking was
      not allowed. RESULTS: Of the 4736 hockey injuries, 3006 (63%) were in Ontario and
      1730 (37%) were in Quebec. Most of the injuries occurred in areas in which
      checking was allowed (3618 [76.4%]) [corrected] At ages 10 to 13, players had
      significantly greater odds of suffering a checking injury where checking was
      allowed (odds ratio [OR]: 2.65 [corrected]; 95% confidence interval [CI]:
      2.21[corrected]-3.18 [corrected]). Players in this age group were also more
      likely to suffer a concussion (OR: 1.53 [corrected]; 95% CI: 0.93 [corrected]
      2.52 [corrected]) or fracture (OR: 1.20 [corrected]; 95% CI: 1.00 [corrected]
      1.47) where checking was allowed. Among older players, when checking was allowed
      in both provinces, there were higher odds (OR: 1.1 [corrected]; 95% CI: 0.94
      [corrected]-1.33 [corrected]) of receiving a checking injury in the province that
      had introduced checking at a younger age, suggesting that there is no protective
      effect from learning to check earlier. CONCLUSIONS: Increased injuries
      attributable to checking were observed where checking was allowed. This study
      supports policies that disallow body checking to reduce ice hockey injuries in
      children.

PMID- 16452324
TI  - Evaluation of a school-based tuberculosis-screening program and associate
      investigation targeting recently immigrated children in a low-burden country.
AB  - CONTEXT: In countries with a low incidence of tuberculosis (TB), screening
      programs targeting recent immigrants from TB-endemic countries have been shown to
      be effective in further reducing TB incidence; however, evaluative data on some
      aspects of these programs remain sparse. OBJECTIVE: We sought to retrospectively
      evaluate a school-based screening program targeting children at high risk for TB
      infection in Montreal, Canada, as well as subsequently investigate family and
      household associates of the schoolchildren with latent TB infection (LTBI), based
      on adherence to LTBI therapy and cost-benefit analysis. DESIGN, SETTING, AND
      PARTICIPANTS: Newly arrived immigrant children (aged 4-18 years) in selected
      schools were screened for LTBI by using the tuberculin skin test (TST). The TST
      was defined as positive at an induration of > or =10 mm. Each child who tested
      positive on the TST was referred for medical evaluation. Family and household
      associates of the TST-positive child also were screened for LTBI. Classroom
      attendance sheets and medical charts were reviewed for 16 elementary and
      secondary schools that comprised the school-screening program of the Montreal
      Children's Hospital from 1998 to 2003. Medical charts of the child associates
      (<18 years old) who were screened were reviewed also. MAIN OUTCOME MEASURES: The
      main outcome measures were TST-positivity rate, rate of adherence to LTBI
      therapy, estimation of factors associated with adherence, and net cost/benefit of
      the school-screening and associate-investigation programs, both respectively and
      as a combined program, compared with the cost of passive treatment of TB disease.
      RESULTS: Of 2524 immigrant children screened, 542 (21%) were TST-positive. Of 342
      children started on therapy, 316 (92%) demonstrated adequate adherence. The only
      predictor of adherence among the schoolchildren was having > or =2 family members
      brought in for TB screening (adjusted odds ratio: 2.0; 95% confidence interval:
      1.3-3.3). There were 599 associates investigated from the 484 TST-positive
      schoolchildren seen at the TB clinic. Of 555 associates with TST results, 211
      (38%) were found to be TST-positive. Of 136 TST-positive child associates, 131
      were seen at the Montreal Children's Hospital TB clinic and had their chart
      reviewed. Of these, 108 (82%) were started on LTBI therapy, and 78 (79%) of 99 of
      those children with information complied adequately with their therapy. We found
      net benefits from both school-based screening and associate investigation, both
      as stand-alone programs and as 1 coordinated, targeted TB-screening program.
      CONCLUSION: We demonstrated the effectiveness, including cost-effectiveness, of a
      targeted, school-based screening program in a low-burden country and the extra
      benefit given by adding associates to such a program.

PMID- 16452325
TI  - Influenza vaccinations of young children increased with media coverage in 2003.
AB  - OBJECTIVE: We sought to evaluate the impact of intense influenza media coverage
      during the 2003-2004 influenza season on the influenza vaccination status of
      children 6 to 59 months of age. METHODS: Children 6 to 59 months of age who
      presented to a large, academic pediatric continuity clinic or affiliated acute
      care clinic in the summer of 2004 were enrolled. A parental survey ascertained
      the influenza vaccination status of the child and family members during the 2003
      2004 influenza season and factors that influenced their vaccination status. For
      children vaccinated in the clinic or health department, influenza vaccination
      dates were confirmed in a computerized medical chart or state immunization
      registry. RESULTS: Of 256 enrolled children, 98 (38%) parents reported that their
      child had received the 2003-2004 influenza vaccine, and 64 (65%) had confirmed
      influenza vaccination dates. Unlike the previous influenza season in which
      confirmed influenza vaccination dates from a similar study population were
      distributed more evenly from October through December, most children (75%) with
      confirmed vaccination dates received the vaccine after the media coverage in mid
      November. Influenza vaccinations per week increased dramatically after the media
      coverage began (2.4 vs 8.6 per week; t test: P < .001). In late November and
      December 2003, the influenza-related media coverage, which focused primarily on
      an early, severe influenza season, increased dramatically and explained 85% of
      the variation in influenza vaccinations. Multivariate analysis showed that
      recalling a physician recommendation (odds ratio [OR]: 6.8; 95% confidence
      interval [CI]: 2.3-19.7), having a family member who had received the influenza
      vaccine (OR: 9.5; 95% CI: 4.3-21.3), having a continuity clinic visit between
      October and January (OR: 4.5; 95% CI: 2.0-10.1), and having a high-risk medical
      condition (OR: 2.9; 95% CI: 1.1-7.8) strongly predicted the influenza vaccination
      status in the children. CONCLUSION: Media coverage in conjunction with explicit
      physician recommendation for children and their contacts are key factors that are
      associated with influenza vaccination rates in children.

PMID- 16452326
TI  - A survey of delivery room resuscitation practices in the United States.
AB  - OBJECTIVE: To determine current resuscitation practices of neonatologists in the
      United States. METHODS: A 15-question survey was developed and mailed to neonatal
      directors in May 2004. RESULTS: Of the total of 797 surveys mailed, 84 were
      returned undeliverable or unanswered and 450 were returned completed (63%
      response rate). Respondents were mainly (70%) from level III NICUs. Most programs
      resuscitate newborns in the delivery room (83%), rather than in a separate room.
      The number and background of individuals attending deliveries vary greatly, with
      31% of programs having <3 individuals attending deliveries. Flow-inflating bags
      are most commonly used (51%), followed by self-inflating bags (40%) and T-piece
      resuscitators (14%). Pulse oximeters are used during resuscitation by 52% of
      programs, and 23% of respondents indicated that there was a useful signal within
      1 minute after application. Blenders are available for 42% of programs, of which
      77% use pure oxygen for the initial resuscitation and 68% use oximeters to alter
      the fraction of inspired oxygen. Thirty-two percent of programs use carbon
      dioxide detectors to confirm intubation, 48% routinely and 43% when there is
      difficulty confirming intubation. Preterm infants are wrapped with plastic wrap
      to prevent heat loss in 29% of programs, of which 77% dry the infant before wrap
      application. A majority of programs (76%) attempt to provide continuous positive
      airway pressure or positive end expiratory pressure (PEEP) during resuscitation,
      most commonly with a flow-inflating bag (58%), followed by a self-inflating bag
      with PEEP valve (19%) and T-piece resuscitator (16%). A level of 5 cm H2O is used
      by 55% of programs. CONCLUSIONS: Substantial variations exist in neonatal
      resuscitation practices, some of which are not addressed in standard guidelines.
      Future guidelines should include recommendations regarding the use of blenders,
      oximeters, continuous positive airway pressure/PEEP, and plastic wrap during
      resuscitation.

PMID- 16452327
TI  - Time well spent? Relating television use to children's free-time activities.
AB  - OBJECTIVES: This study assessed the claim that children's television use
      interferes with time spent in more developmentally appropriate activities.
      METHODS: Data came from the first wave of the Child Development Supplement, a
      nationally representative sample of children aged 0 to 12 in 1997 (N = 1712).
      Twenty-four-hour time-use diaries from 1 randomly chosen weekday and 1 randomly
      chosen weekend day were used to assess children's time spent watching television,
      time spent with parents, time spent with siblings, time spent reading (or being
      read to), time spent doing homework, time spent in creative play, and time spent
      in active play. Ordinary least squares multiple regression was used to assess the
      relationship between children's television use and time spent pursuing other
      activities. RESULTS: Results indicated that time spent watching television both
      with and without parents or siblings was negatively related to time spent with
      parents or siblings, respectively, in other activities. Television viewing also
      was negatively related to time spent doing homework for 7- to 12-year-olds and
      negatively related to creative play, especially among very young children
      (younger than 5 years). There was no relationship between time spent watching
      television and time spent reading (or being read to) or to time spent in active
      play. CONCLUSIONS: The results of this study are among the first to provide
      empirical support for the assumptions made by the American Academy of Pediatrics
      in their screen time recommendations. Time spent viewing television both with and
      without parents and siblings present was strongly negatively related to time
      spent interacting with parents or siblings. Television viewing was associated
      with decreased homework time and decreased time in creative play. Conversely,
      there was no support for the widespread belief that television interferes with
      time spent reading or in active play.

PMID- 16452328
TI  - Behavior problems among inner-city children with asthma: findings from a
      community-based sample.
AB  - OBJECTIVE: Previous studies have suggested a relationship between childhood
      asthma and behavior problems. However, few studies have used community-based
      samples to assess the prevalence of behavior problems among urban children with
      asthma symptoms. The objective of this study was to evaluate the relationship
      between asthma symptoms and behavior among a population-based sample of inner
      city children and to determine the prevalence of behavioral comorbidity among
      children with asthma symptoms. METHODS: In 2003, parents of children who were
      entering kindergarten in the city of Rochester completed a detailed survey
      regarding the child's background, medical history (with specific questions about
      asthma symptoms), and behavior. We compared children with no asthma symptoms,
      intermittent symptoms, and persistent symptoms with regard to positive peer
      social skills (eg, makes friends easily), negative peer social skills (eg, fights
      with other children), task orientation (eg, concentrates well), and shy/anxious
      behavior (eg, is withdrawn) (validated scales; range: 1-4). We used multivariate
      regression to determine the independent association between symptom severity and
      behavioral outcomes. RESULTS: A total of 1619 children were included (response
      rate: 80%; mean age: 5.1 year), and 15% had asthma symptoms (8% persistent, 7%
      intermittent). Average negative peer scores were worse for children with
      persistent asthma symptoms compared with children with intermittent and no
      symptoms (mean scores: 1.88, 1.70, and 1.65). Children with persistent symptoms
      also scored worse than children with no symptoms on the assessment of task
      orientation (2.85 vs 3.03) and shy/anxious behavior (2.11 vs 1.89). Among
      children with persistent asthma symptoms, >20% scored >1 SD below average on 2 or
      more scales, compared with 16% of children with intermittent symptoms and 10%
      with no symptoms. CONCLUSIONS: Urban children with persistent asthma symptoms
      demonstrate more behavior problems across several domains compared with children
      with no symptoms. These findings suggest a clear need for an early
      biopsychosocial approach to care for vulnerable children with asthma.

PMID- 16452330
TI  - Weight teasing and disordered eating behaviors in adolescents: longitudinal
      findings from Project EAT (Eating Among Teens).
AB  - OBJECTIVE: To assess whether weight-related teasing predicts the development of
      binge eating, unhealthy weight control behaviors, and frequent dieting among male
      and female adolescents. METHODS: A prospective study was conducted with an
      ethnically and socioeconomically diverse sample of 2516 adolescents who completed
      surveys at both time 1 (1998-1999) and time 2 (2003-2004) of the Project EAT
      (Eating Among Teens) study. RESULTS: In 1998-1999, approximately one fourth of
      participants reported being teased about their weight at least a few times a
      year. After adjustment for age, race/ethnicity, socioeconomic status (SES), and
      BMI, boys who were teased about their weight were more likely than their peers to
      initiate binge eating with loss of control and unhealthy weight control behaviors
      5 years later. The predicted prevalence for incident binge eating behaviors with
      loss of control among boys who were teased was 4.1% as compared with 1.4% for
      those who were not teased, after adjustment for age, race/ethnicity, SES, and
      BMI. For unhealthy weight control behaviors at time 2, the predicted prevalence
      was 27.5% among boys who were teased and 19.3% for boys who were not teased,
      after adjustment for age, race/ethnicity, SES, and BMI. Girls who were teased
      were more likely than their peers to become frequent dieters. The predicted
      prevalence for incident frequent dieting among girls who were teased was 18.2% as
      compared with 11.0% for those who were not teased, after adjustment for age,
      race/ethnicity, SES, and BMI. CONCLUSIONS: Weight teasing in adolescence predicts
      disordered eating behaviors at 5-year follow-up. The patterns of these
      associations differ by gender. Reducing teasing through educational interventions
      and policies may reduce the level of disordered eating behaviors among youths.

PMID- 16452329
TI  - Increases in overweight after adenotonsillectomy in overweight children with
      obstructive sleep-disordered breathing are associated with decreases in motor
      activity and hyperactivity.
AB  - OBJECTIVE: To examine the effect of adenotonsillectomy (T&A) in children with
      obstructive sleep-disordered breathing on growth, hyperactivity, and sleep and
      waking motor activity. METHODS: We studied 54 children who were aged 6 to 12
      years and had adenotonsillar hypertrophy and an obstructive apnea-hypopnea index
      of > or =1 before and 12 months after they all received adenotonsillectomy (T&A).
      We measured their height, weight, percentage overweight (patient BMI - BMI at
      50th percentile)/BMI at 50th percentile x 100) and obtained a hyperactivity score
      from parent report on a standardized behavior questionnaire scale. A subset of 21
      of these children were also studied for motor activity by wrist actigraphy for 7
      consecutive days and nights before and 12 months after T&A. RESULTS: After T&A,
      mean obstructive apnea-hypopnea index decreased from 7.6 to 0.6. Height
      percentile did not change, but weight percentile increased; as a consequence,
      percentage overweight increased from 32.0% to 36.3%. Hyperactivity scores and
      total daily motor activity were reduced after T&A. From linear regression, the
      reduction in hyperactivity scores predicted an increase in percentage overweight.
      Reduced motor activity was correlated with increased percentage overweight.
      CONCLUSIONS: An increase in percentage overweight after T&A in children with
      obstructive sleep-disordered breathing is correlated to decreased child
      hyperactivity scores and to decreased measured motor activity in the subset
      studied. These associations suggest that the increase in overweight may be
      attributable to reductions in physical activity and fidgeting energy expenditure.

PMID- 16452331
TI  - Effect of maternal multivitamin supplementation on the mental and psychomotor
      development of children who are born to HIV-1-infected mothers in Tanzania.
AB  - OBJECTIVES: To determine the association between maternal multivitamin
      supplementation and the mental and psychomotor development of children who are
      born to HIV-1-infected mothers in Tanzania, as secondary endpoints in a
      randomized trial that investigated the effect of maternal multivitamin
      supplementation on HIV-1 vertical transmission and progression. METHODS: The
      Bayley Scales of Infant Development, 2nd Edition, were administered at 6, 12, and
      18 months of age to a subset of children (N = 327). We assessed the effect of
      vitamin A and multivitamin (vitamins B, C, and E) supplementation using linear
      regression models and Cox proportional hazard models for the Mental Development
      Index, the Psychomotor Development Index, and raw scores separately. RESULTS:
      Multivitamin supplementation was associated significantly with a mean increase in
      Psychomotor Development Index score of 2.6 (95% confidence interval: 0.1-5.1).
      Multivitamins were also significantly protective against the risk for
      developmental delay on the motor scale (relative risk: 0.4; 95% confidence
      interval: 0.2-0.7) but not on the Mental Development Index. Vitamin A
      supplementation had no significant effect on these outcomes. CONCLUSIONS:
      Maternal multivitamin supplements provide a low-cost intervention to reduce the
      risk for developmental delays among infants who are born to HIV-positive mothers
      in developing countries.

PMID- 16452332
TI  - Project Universal Preschool Vision Screening: a demonstration project.
AB  - OBJECTIVES: Visual disorders among preschool-aged children are common, yet
      screening is infrequent. The purpose of this project was to implement the vision
      screening recommendations proposed by the Maternal and Child Health Bureau and
      National Eye Institute Vision Screening in the Preschool Child Task Force:
      monocular visual acuity and stereopsis testing. METHODS: Four sites fully
      participated in the implementation of the task force recommendations with 3- and
      4-year-old children. Two of the sites worked with primary care practices (testing
      performed by staff); 2 worked with community-based programs (testing performed by
      lay volunteers). Each site tracked number of children screened by age, as well as
      proportion testable, referred, and with documented follow-up evaluation. RESULTS:
      Variations in implementation of the recommendations were observed. Successful
      screening among 3-year-olds ranged from 70% to 93%; referral rates were 1% to
      41%, and follow-up rates were 29% to 100%. Successful screening among 4-year-olds
      ranged from 88% to 98%; referral rates were 2% to 40%, and follow-up rates were
      41% to 100%. The proportion of 3-year-olds who were treated was significantly
      different between the community-based sites (n = 20) and the primary care sites
      (n = 2). Similarly, the proportion of 4-year-olds who were treated was
      significantly different between the community-based sites (n = 36) and the
      primary care sites (n = 11). CONCLUSION: . The variability across pilot sites in
      numbers successfully screened and numbers referred suggests that all aspects of
      preschool vision screening need thorough review before the goal of universal
      preschool vision screening can be realized.

PMID- 16452333
TI  - Epidemiology of DSM-IV insomnia in adolescence: lifetime prevalence, chronicity,
      and an emergent gender difference.
AB  - OBJECTIVE: The confluence of sleep/wake cycle and circadian rhythm changes that
      accompany pubertal development and the social and emotional developmental tasks
      of adolescence may create a period of substantial risk for development of
      insomnia. Although poor sleep affects cognitive performance and is associated
      with poor emotional and physical health, epidemiologic studies among adolescents
      have been limited. In this first epidemiologic study of insomnia defined by
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      criteria in a US sample of adolescents, we estimated lifetime prevalence of
      insomnia, examined chronicity and onset, and explored the role of pubertal
      development. METHODS: Data come from a random sample of 1014 adolescents who were
      13 to 16 years of age, selected from households in a 400000-member health
      maintenance organization encompassing metropolitan Detroit. Response rate was
      71.2%. The main outcome measured was DSM-IV-defined insomnia. RESULTS: Lifetime
      prevalence of insomnia was 10.7%. A total of 88% of adolescents with a history of
      insomnia reported current insomnia. The median age of onset of insomnia was 11.
      Of those with insomnia, 52.8% had a comorbid psychiatric disorder. In exploratory
      analyses of insomnia and pubertal development, onset of menses was associated
      with a 2.75-fold increased risk for insomnia. There was no difference in risk for
      insomnia among girls before menses onset relative to boys, but a difference
      emerged after menses onset. In contrast, maturational development was not
      associated with insomnia in boys. CONCLUSIONS: Insomnia seems to be common and
      chronic among adolescents. The often found gender difference in risk for insomnia
      seems to emerge in association with onset of menses.

PMID- 16452334
TI  - Influenza among healthy young children: changes in parental attitudes and
      predictors of immunization during the 2003 to 2004 influenza season.
AB  - BACKGROUND: In Colorado, the 2003 to 2004 influenza season was unusually early
      and severe and received substantial media attention. OBJECTIVES: Among parents of
      healthy young children, to determine how parental knowledge and attitudes
      regarding influenza infection and immunization changed during the 2003 to 2004
      influenza season and to identify factors predictive of influenza immunization.
      METHODS: The study was conducted in 5 metropolitan Denver pediatric practices. A
      total of 839 healthy children age 6 to 21 months and their parents were randomly
      selected for participation. Parents were surveyed by telephone before (August 18
      to October 7, 2003) and after (March 31 to June 10, 2004) the influenza season.
      RESULTS: Among 828 eligible parents, 472 (57%) completed the preseason survey;
      316 (67%) of these parents subsequently completed the postseason survey. All
      analyses were performed for the 316 subjects who completed both preseason and
      postseason surveys. Compared with their attitudes before the influenza season,
      48% of parents interviewed after the season viewed their child as more
      susceptible to influenza, 58% viewed influenza infections as more severe, and 66%
      perceived fewer risks associated with influenza vaccine. Ninety-five percent of
      parents reported hearing in the media about Colorado's influenza outbreak, and
      having heard about the outbreak in the media was associated with viewing
      influenza infections as more severe. A total of 258 parents (82%) immunized their
      child against influenza. In multivariate analyses, positive predictors of
      immunization included a physician recommendation for immunization and a preseason
      to postseason increase in the perception that immunization was the social norm.
      Negative predictors of immunization included high perceived barriers to
      immunization, less parental education, and preseason intention not to immunize.
      CONCLUSIONS: Parent attitudes about influenza infection and immunization changed
      substantially during the 2003 to 2004 influenza season, with changes favoring
      increased parental acceptance of influenza vaccination for young children. During
      an intensively publicized influenza outbreak, a physician recommendation of
      vaccination was an important predictor of influenza immunization.

PMID- 16452335
TI  - Physical health outcomes of childhood exposure to intimate partner violence: a
      systematic review.
AB  - BACKGROUND: Children exposed to intimate partner violence (IPV) are at increased
      risk for adverse mental and behavioral health sequelae, as has been documented by
      both systematic reviews and meta-analyses. Studies addressing the physical health
      impact of childhood IPV exposure, however, have not been summarized in a manner
      that might facilitate additional hypothesis-driven research and accelerate the
      development of targeted interventions. METHODS: To identify a comprehensive set
      of articles examining the association between childhood IPV exposure and physical
      health, we searched online bibliographic databases including Medline, CINAHL,
      PsychInfo, and Sociological Abstracts using the keywords "domestic" or "intimate
      partner violence" and "infant," "child," or "pediatric." From >2000 articles
      retrieved in the initial search, we used online abstract and bibliographic
      information to identify 94 articles potentially meeting the inclusion criteria of
      studies that (1) examined a postnatal physical health outcome related to IPV
      exposure and (2) had a contemporaneous control group. Thorough review of these 94
      published studies yielded 22 that met these inclusion criteria. The data then
      were abstracted independently by 2 of the authors, and differences were settled
      with the assistance of a third author. RESULTS: Childhood exposure to IPV
      increases the likelihood of risk-taking behaviors during adolescence and
      adulthood and is likely associated with underimmunization. Minimal data and study
      limitations preclude establishing a clear connection between IPV exposure and
      general health and use of health services, breastfeeding, or weight gain.
      CONCLUSIONS: The impact on physical health from exposure to IPV during childhood
      is still uncertain. Future studies should be grounded in a theoretical model that
      specifies how IPV exposure can affect child health, should adjust for confounders
      adequately, should include a community-based sample, and should be of larger
      scale.

PMID- 16452336
TI  - Association between bone density and fractures in children: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: The objective of this article was to systematically review all
      published studies that investigated the association between bone density and
      fractures in children. DESIGN: Potentially relevant articles were identified by
      searching electronic databases. Duplicates were removed, abstracts were
      inspected, and relevant articles were obtained. Studies were included in the
      systematic review if participants were <16.0 years old, were healthy, had
      extractable data on bone mass, and had fractures as the outcome. RESULTS: Ten
      case-control studies were identified. No prospective studies were found. There
      was no evidence of heterogeneity between studies or of funnel-plot asymmetry.
      Eight of the studies were included in the meta-analysis, because they presented
      results as means and standard deviations of bone density in cases and controls.
      The pooled standardized mean difference for bone mass in children with and
      without fractures, from a fixed-effects model, was -0.32 (95% confidence
      interval: -0.43 to -0.21). CONCLUSIONS: Evidence for an association between bone
      density and fractures in children is limited. The results from this meta-analysis
      suggest that there is an association between low bone density and fractures in
      children. Although there was no evidence of heterogeneity or publication bias,
      this meta-analysis is based on case-control studies that are prone to bias.
      Large, well-conducted prospective cohort studies are required to confirm the
      association between bone density and fractures in children.

PMID- 16452338
TI  - Hot brains: manipulating body heat to save the brain.

PMID- 16452337
TI  - Screening for speech and language delay in preschool children: systematic
      evidence review for the US Preventive Services Task Force.
AB  - BACKGROUND: PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
      Published in the public domain by the American Academy of Pediatrics. Speech and
      language development is a useful indicator of a child's overall development and
      cognitive ability and is related to school success. Identification of children at
      risk for developmental delay or related problems may lead to intervention
      services and family assistance at a young age, when the chances for improvement
      are best. However, optimal methods for screening for speech and language delay
      have not been identified, and screening is practiced inconsistently in primary
      care. PURPOSE: We sought to evaluate the strengths and limits of evidence about
      the effectiveness of screening and interventions for speech and language delay in
      preschool-aged children to determine the balance of benefits and adverse effects
      of routine screening in primary care for the development of guidelines by the US
      Preventive Services Task Force. The target population includes all children up to
      5 years old without previously known conditions associated with speech and
      language delay, such as hearing and neurologic impairments. METHODS: Studies were
      identified from Medline, PsycINFO, and CINAHL databases (1966 to November 19,
      2004), systematic reviews, reference lists, and experts. The evidence review
      included only English-language, published articles that are available through
      libraries. Only randomized, controlled trials were considered for examining the
      effectiveness of interventions. Outcome measures were considered if they were
      obtained at any time or age after screening and/or intervention as long as the
      initial assessment occurred while the child was < or =5 years old. Outcomes
      included speech and language measures and other functional and health outcomes
      such as social behavior. A total of 745 full-text articles met our eligibility
      criteria and were reviewed. Data were extracted from each included study,
      summarized descriptively, and rated for quality by using criteria specific to
      different study designs developed by the US Preventive Services Task Force.
      RESULTS: The use of risk factors for selective screening has not been evaluated,
      and a list of specific risk factors to guide primary care physicians has not been
      developed or tested. Sixteen studies about potential risk factors for speech and
      language delay in children enrolled heterogeneous populations, had dissimilar
      inclusion and exclusion criteria, and measured different risk factors and
      outcomes. The most consistently reported risk factors included a family history
      of speech and language delay, male gender, and perinatal factors. Other risk
      factors reported less consistently included educational levels of the mother and
      father, childhood illnesses, birth order, and family size. The performance
      characteristics of evaluation techniques that take < or =10 minutes to administer
      were described in 24 studies relevant to screening. Studies that were rated good
      to fair quality reported wide ranges of sensitivity and specificity when compared
      with reference standards (sensitivity: 17-100%; specificity: 45-100%). Most of
      the evaluations, however, were not designed for screening purposes, the
      instruments measured different domains, and the study populations and settings
      were often outside of primary care. No "gold standard" has been developed and
      tested for screening, reference standards varied across studies, few studies
      compared the performance of > or =2 screening techniques in 1 population, and
      comparisons of a single screening technique across different populations are
      lacking. Fourteen good- and fair-quality randomized, controlled trials of
      interventions reported significantly improved speech and language outcomes
      compared with control groups. Improvement was demonstrated in several domains
      including articulation, phonology, expressive language, receptive language,
      lexical acquisition, and syntax among children in all age groups studied and
      across multiple therapeutic settings. Improvement in other functional outcomes
      such as socialization skills, self-esteem, and improved play themes were
      demonstrated in some, but not all, of the 4 studies that measured them. In
      general, studies of interventions were small and heterogeneous, may be subject to
      plateau effects, and reported short-term outcomes based on various instruments
      and measures. As a result, long-term outcomes are not known, interventions could
      not be compared directly, and generalizability is questionable. CONCLUSIONS: Use
      of risk factors to guide selective screening is not supported by studies. Several
      aspects of screening have been inadequately studied to determine optimal methods,
      including which instrument to use, the age at which to screen, and which interval
      is most useful. Trials of interventions demonstrate improvement in some outcome
      measures, but conclusions and generalizability are limited. Data are not
      available addressing other key issues including the effectiveness of screening in
      primary care settings, role of enhanced surveillance by primary care physicians
      before referral for diagnostic evaluation, non-speech and language and long-term
      benefits of interventions, and adverse effects of screening and interventions.

PMID- 16452339
TI  - Of lobsters, electronic medical records, and neonatal total parenteral nutrition.
AB  - At the Mayo Health System in LaCrosse, Wisconsin, there are >1000 infant total
      parenteral nutrition (TPN) orders placed per year. It is the most complicated
      order that the pharmacy fills, so a recent peer-review article in Pediatrics
      moved a group of us to action at our center to buy or develop a TPN calculator.
      We did this because no stand-alone commercial calculators were available to us,
      and expensive electronic medical records typically do not include TPN calculators
      for neonatal patients. The new software includes decision support, and the orders
      are consistently legible. The physician performs fewer calculations, and there
      are no mathematical errors. This article examines the broader significance of
      providers having to write their own TPN software.

PMID- 16452340
TI  - Visceral larva migrans associated with earthworm ingestion: clinical evolution in
      an adolescent patient.
AB  - A 16-year-old girl developed a cough, hypereosinophilia (absolute eosinophil
      count: 32000/mm3), hypergammaglobulinemia, and multiple noncavitary pulmonary
      nodules 1 month after having ingested an earthworm on a dare. Spirometry revealed
      moderate restriction and reduced gas diffusion. Parabronchial biopsy demonstrated
      eosinophilic organizing pneumonitis with multiple eosinophilic microabscesses,
      and Toxocara titers were elevated (>1:4096). Ophthalmologic examination ruled out
      ocular larva migrans. The patient received a 10-day course of albendazole (400 mg
      orally twice daily) and demonstrated significant clinical improvement with
      resolution of cough and pulmonary function abnormalities. Her white blood cell
      count and hypergammaglobulinemia normalized within 20 days, yet eosinophils
      (absolute eosinophil count: 1780/mm3) and Toxocara serologies (>1:4096) remained
      elevated 3 months after completing antihelminthic therapy. In this instance, the
      ingested earthworm served as the paratenic carrier of Toxocara larvae from the
      soil to the patient. This case highlights the clinical evolution of pulmonary
      visceral larva migrans infection caused by Toxocara spp. associated with a
      discrete ingestion in an adolescent patient. In addition, it provides a rare
      opportunity to define the incubation period of visceral larva migrans and
      emphasizes the importance of education regarding sources of Toxocara infection.

PMID- 16452341
TI  - The pediatrician and disaster preparedness.
AB  - For decades, emergency planning for natural disasters, public health emergencies,
      workplace accidents, and other calamities has been the responsibility of
      government agencies on all levels and certain nongovernment organizations such as
      the American Red Cross. In the case of terrorism, however, entirely new
      approaches to emergency planning are under development for a variety of reasons.
      Terrorism preparedness is a highly specific component of general emergency
      preparedness. In addition to the unique pediatric issues involved in general
      emergency preparedness, terrorism preparedness must consider several additional
      issues, including the unique vulnerabilities of children to various agents as
      well as the limited availability of age- and weight-appropriate antidotes and
      treatments. Although children may respond more rapidly to therapeutic
      intervention, they are at the same time more susceptible to various agents and
      conditions and more likely to deteriorate if they are not monitored carefully.
      This article is designed to provide an overview of key issues for the
      pediatrician with respect to disaster, terrorism, and public health emergency
      preparedness. It is not intended to be a complete compendium of didactic content
      but rather offers an approach to what pediatricians need to know and how
      pediatricians must lend their expertise to enhance preparedness in every
      community. To become fully and optimally prepared, pediatricians need to become
      familiar with these key areas of emergency preparedness: unique aspects of
      children related to terrorism and other disasters; terrorism preparedness; mental
      health vulnerabilities and development of resiliency; managing family concerns
      about terrorism and disaster preparedness; office-based preparedness; hospital
      preparedness; community, government, and public health preparedness; and
      advocating for children and families in preparedness planning.

PMID- 16452342
TI  - Wide geographic variation between Pennsylvania counties in the population rates
      of hospital admissions for pneumonia among children with and without comorbid
      chronic conditions.
AB  - OBJECTIVES: To compare county rates of hospital admissions for pediatric
      pneumonia and to assess the contribution of comorbid chronic conditions to county
      and state pediatric pneumonia admission rates. METHODS: We performed
      retrospective analyses of data for all Pennsylvania-resident children 2 months
      through 17 years of age who were admitted to acute care hospitals with a
      principal diagnosis of pneumonia in 2003 or 2004. We divided the admissions into
      2 groups (all pneumonia and pneumonia excluding coded comorbid chronic
      conditions) and calculated admission rates for each Pennsylvania county. RESULTS:
      There were 5429 pediatric pneumonia admissions during the 12-month study period,
      of which 4948 (91.1%) were included in the study. The Pennsylvania state
      admission rate for all pneumonia was 156.3 admissions per 100000 children. County
      admission rates for all pneumonia ranged from 77.0 admissions per 100000 children
      to 457.6 admissions per 100000 children. Similar geographic patterns were seen
      among the 2851 admissions that remained in the second group after the exclusion
      of 2097 records (42.4%) coded for comorbid chronic conditions. The Pennsylvania
      state admission rate for pneumonia without chronic conditions was 90.0 admissions
      per 100000 children. County admission rates for pneumonia without comorbid
      chronic conditions ranged from 18.3 admissions per 100000 children to 350.3
      admissions per 100000 children. Sixty-two (93%) of 67 counties remained in the
      same or an adjacent admission rate quintile after children with comorbid chronic
      conditions were excluded. On average, the county admission rates for pneumonia
      without comorbid chronic conditions were 58.1% of their admission rates for all
      pneumonia. CONCLUSIONS: County pediatric pneumonia admission rates vary widely,
      even among geographically contiguous and demographically similar counties.
      Excluding children with comorbid chronic conditions, to control for varying
      community disease burdens, did not alter substantially the county rank order or
      the pattern or degree of variations in admission rates in our study.

PMID- 16452343
TI  - A combination measles, mumps, rubella, and varicella vaccine (ProQuad) given to 4
      to 6-year-old healthy children vaccinated previously with M-M-RII and Varivax.
AB  - BACKGROUND: In the United States, children receive primary doses of M-M-RII
      (Merck & Co, Inc, West Point, PA) and Varivax (Merck & Co, Inc) beginning at 12
      months, often at the same health care visit. Currently a second dose of M-M-RII
      is given to 4- to 6-year-old children, to increase vaccination rates and to
      reduce the number of individuals without detectable antibodies. A second dose of
      a varicella-containing vaccine may result in similar benefits. OBJECTIVES: To
      demonstrate that ProQuad (measles, mumps, rubella, and varicella virus vaccine
      live; Merck & Co, Inc) may be given in place of a second dose of M-M-RII or
      second doses of M-M-RII and Varivax for 4- to 6-year-old children. METHODS: Four-
      to 6-year-old children who had been immunized previously with M-M-RII and Varivax
      were assigned randomly to receive either ProQuad and placebo (N = 399), M-M-RII
      and placebo (N = 195), or M-M-RII and Varivax (N = 205) and were then monitored
      for safety and immunogenicity. RESULTS: ProQuad was generally well tolerated.
      Similarity (noninferiority) was demonstrated in postvaccination antibody
      responses to measles, mumps, and rubella between recipients of ProQuad and all
      recipients of M-M-RII and in responses to varicella between recipients of ProQuad
      and recipients of Varivax. Postvaccination seropositivity rates for antibodies
      against all 4 viruses were nearly 100% in all 3 groups. Small fold increases were
      observed for measles, mumps, and rubella antibody titers. In contrast,
      substantial boosts in varicella antibody titers were observed among recipients of
      a second dose of varicella vaccine, administered as ProQuad or Varivax.
      CONCLUSIONS: ProQuad may be used in place of a second dose of M-M-RII or second
      doses of M-M-RII and Varivax for 4- to 6-year-old children.

PMID- 16452344
TI  - Quality of life for children and adolescents: impact of HIV infection and
      antiretroviral treatment.
AB  - BACKGROUND: HIV/AIDS mortality rates in the United States are declining;
      pediatric HIV has become a chronic disease, with quality of life (QoL) outcomes
      assuming greater importance. OBJECTIVES: To compare QoL among HIV-infected and
      uninfected children and to assess the impact of different antiretroviral regimens
      on QoL among HIV-infected children. METHODS: Perinatally exposed, HIV-infected (N
      = 1847) and uninfected (N = 712) children and adolescents were studied. Among
      infected children, 1283 were available for the antiretroviral regimen analysis.
      QoL domain scores were assessed for subjects 6 months to 4 years, 5 to 11 years,
      and 12 to 21 years of age, and the impact of infection status and alternative
      treatment regimens on QoL domains was evaluated. RESULTS: HIV infection was
      associated with significantly worse mean adjusted scores for functional status
      among children 6 months to 4 years of age and health perceptions, physical
      resilience, physical functioning, and social/role functioning among those 5 to 11
      years of age. However, uninfected children 5 to 11 years of age reported
      significantly worse psychological functioning. HIV-infected children (5-11 years
      of age) and adolescents (12-21 years of age) receiving no antiretroviral
      treatment had worse health perceptions. Adolescents receiving no antiretroviral
      agents also had worse symptoms. When antiretroviral regimens were compared,
      adolescents receiving protease inhibitor plus nonnucleoside reverse transcriptase
      inhibitor-containing therapy had worse symptoms, compared with those receiving
      protease inhibitor-containing therapy; otherwise, no significant differences were
      found. CONCLUSIONS: Generally parents of HIV-infected children 6 months to 4
      years and 5 to 11 years of age generally reported lower mean QoL scores than did
      parents of uninfected children, although worse psychological functioning was
      reported for uninfected children. HIV-infected adolescents not receiving
      antiretroviral treatment had worse health perceptions and symptoms. We found no
      consistent QoL differences among children receiving different antiretroviral
      regimens.

PMID- 16452345
TI  - Shortcomings in infant iron deficiency screening methods.
AB  - BACKGROUND: Screening for iron deficiency anemia is a well-established practice
      in pediatrics, but numerous challenges surrounding current recommendations raise
      questions about the effectiveness of this strategy. OBJECTIVE: To evaluate iron
      deficiency anemia screening approaches, by assessing rates of follow-up testing
      and resolution among patients meeting screening criteria in a primary care
      setting. METHODS: A retrospective cohort study was performed. We extracted
      electronic medical record data on complete blood counts for infants who received
      primary care in our clinics in the past 10 years. We calculated rates of positive
      screening results with 9 different measurement criteria and determined rates of
      follow-up testing and of documented correction of iron deficiency among those who
      screened positive. RESULTS: Our cohort consisted of 4984 children who were
      screened at 9 to 15 months of age, between 1994 and 2004. There was a wide
      distribution of positive detection rates (range: 1.5-14.5%) among the 9 screening
      criteria. Follow-up testing rates were low. No more than 25% of infants who
      screened positive by any criterion underwent a repeat complete blood count within
      6 months. Moreover, no more than 11.6% (range: 4.4-11.6%) had documented
      correction of their laboratory abnormalities. CONCLUSIONS: Significant
      shortcomings exist in current iron deficiency anemia screening practices. A
      widely agreed-on, specific, and inexpensive screening criterion, with increased
      emphasis on systems-based approaches to iron deficiency screening, is needed.

PMID- 16452346
TI  - Acute and sustained effects of lucinactant versus poractant-alpha on pulmonary
      gas exchange and mechanics in premature lambs with respiratory distress syndrome.
AB  - BACKGROUND: Animal-derived, protein-containing surfactants seem to be superior to
      protein-free surfactants. Lucinactant, a synthetic surfactant containing a
      surfactant protein-B peptide analog, has been shown to be effective in animal
      models and phase II clinical trials. To date, lucinactant has not been compared
      with an animal-derived surfactant in a premature animal model. OBJECTIVE: The
      objective was to compare the acute and sustained effects of lucinactant among
      premature lambs with respiratory distress syndrome (RDS) with the effects of a
      natural porcine surfactant (poractant-alpha). METHODS: After 5 minutes of
      mechanical ventilation twin premature lambs were assigned randomly to the
      lucinactant group (30 mg/mL, 5.8 mL/kg) or the poractant-alpha group (80 mg/mL,
      2.2 mL/kg). Heart rate, systemic arterial pressure, arterial pH, blood gas
      values, and lung mechanics were recorded for 12 hours. RESULTS: Baseline fetal pH
      values were similar for the 2 groups (pH 7.27). After 5 minutes of mechanical
      ventilation, severe RDS developed (pH: <7.08; Paco2: >80 mm Hg; Pao2: <40 mm Hg;
      dynamic compliance: <0.08 mL/cm H2O per kg). After surfactant instillation,
      similar improvements in gas exchange and lung mechanics were observed for the
      lucinactant and poractant-alpha groups at 1 hour (pH: 7.3 +/- 0.1 vs 7.4 +/- 0.1;
      Paco2: 8 +/- 18 mm Hg vs 40 +/- 8 mm Hg; Pao2: 167 +/- 52 mm Hg vs 259 +/- 51 mm
      Hg; dynamic compliance: 0.3 +/- 0.1 mL/cm H2O per kg vs 0.3 +/- 0.1 mL/cm H2O per
      kg). The improvements in lung function were sustained, with no differences
      between groups. Cardiovascular profiles remained stable in both groups.
      CONCLUSIONS: Among preterm lambs with severe RDS, lucinactant produced
      improvements in gas exchange and lung mechanics similar to those observed with a
      porcine-derived surfactant.

PMID- 16452347
TI  - Risk of intracranial pathologic conditions requiring emergency intervention after
      a first complex febrile seizure episode among children.
AB  - OBJECTIVE: To determine the likelihood of intracranial pathologic conditions
      requiring emergency neurosurgical or medical intervention among children without
      meningitis who presented to the pediatric emergency department after a first
      complex febrile seizure. METHODS: We performed a retrospective review of
      prospectively collected data for children in neurologically normal condition who
      presented to a single pediatric emergency department after a first complex
      febrile seizure (focal, multiple, or prolonged). The complex febrile seizure
      classification was determined independently by 2 epileptologists. The presence of
      intracranial pathologic conditions was determined through review of neuroimaging
      results, telephone interviews, or medical record review. RESULTS: Data for 71
      children with first complex febrile seizures were analyzed. Fifty-one (72%) had a
      single complex feature (20 focal, 22 multiple, and 9 prolonged), and 20 (28%) had
      multiple complex features. None of the 71 patients (1-sided 95% confidence
      interval: 4%) had intracranial pathologic conditions that required emergency
      neurosurgical or medical intervention. CONCLUSIONS: For children with first
      complex febrile seizures, the risk of intracranial pathologic conditions that
      require emergency neurosurgical or medical intervention is low, which suggests
      that routine emergency neuroimaging for this population is unnecessary.

PMID- 16452348
TI  - Personality in young adults who are born preterm.
AB  - INTRODUCTION: Very preterm birth (VPT; <33 weeks' gestation) is associated with
      later neuromotor and cognitive impairment, reduced school performance, and
      psychiatric morbidity. Several follow-up studies have demonstrated increased
      anxiety and social rejection and reduced self-esteem in preterm children and
      adolescents, but few studies have examined the effects of preterm birth on adult
      personality. METHODS: We assessed 108 VPT individuals and 67 term-born controls
      at ages 18 to 19 years with the Eysenck Personality Questionnaire-Revised, short
      form (EPQ-RS). This questionnaire rates 3 dimensions of personality: extraversion
      (sociability, liveliness, sensation seeking); neuroticism (anxiety, low mood, low
      self-esteem); and psychoticism (coldness, aggression, predisposition to
      antisocial behavior). A fourth scale, "lie," which measures dissimulation, is
      also derived. RESULTS: VPT individuals had significantly lower extraversion
      scores, higher neuroticism scores, and higher lie scores than term-born controls,
      after controlling for age at assessment and socioeconomic status. P scores were
      not significantly different between the 2 groups. There was a gender difference
      in that the increased neuroticism and decreased extraversion scores were
      accounted for mainly by VPT females. Associations between EPQ-RS scores and
      neonatal status, adolescent behavioral ratings, and body size at 18 to 19 years
      were assessed by using Kendall partial correlations, correcting for age at
      assessment and socioeconomic status. Gestational age, indices of neonatal
      hypoxia, and neonatal ultrasound ratings were not correlated with EPQ-RS scores.
      Birth weight was weakly associated with increased lie scores. Rutter Parents'
      Scale score, a measure of adolescent psychopathology, was associated with an
      increased neuroticism score. Poor social adjustment in adolescence was associated
      with an increased lie score. Height and weight at 18 to 19 years were not
      associated with EPQ-RS, but reduced occipitofrontal circumference was associated
      with both decreased extraversion and increased lie scores. CONCLUSIONS: Young
      adults who are born VPT have different personality styles from their term-born
      peers. This may be associated with an increased risk of psychiatric difficulties.

PMID- 16452349
TI  - Child outcomes and family characteristics 1 year after severe inflicted or
      noninflicted traumatic brain injury.
AB  - OBJECTIVE: To assess outcomes 1 year after severe traumatic brain injury (TBI)
      among young children and to compare outcomes between children with inflicted
      versus noninflicted injuries. STUDY DESIGN: Prospective cohort study. METHODS:
      All North Carolina-resident children who were hospitalized between January 2000
      and December 2001 in any of the state's 9 PICUs and who survived a severe TBI
      that occurred on or before their second birthday were eligible to participate.
      Child health status, child use of ancillary medical resources, and family
      characteristics were determined through maternal caregiver interviews
      approximately 1 year after injury. Comparisons were made between family
      characteristics and child outcomes according to injury type. RESULTS: Seventy-two
      interviews of maternal caregivers were completed among 112 survivors (64.3%).
      Children with inflicted injuries (n = 41) had worse outcomes than did children
      with noninflicted injuries (n = 31), as measured with the Pediatric Outcome
      Performance Category and Stein-Jessup Functional Status II (Revised) tools.
      However, approximately 50% of children with inflicted injuries had only mild
      deficits or better. Children with inflicted injuries had a higher use of
      ancillary medical resources. Families caring for the children did not differ
      substantively, with a large proportion of single, working, minority mothers.
      CONCLUSIONS: Children with inflicted TBIs had worse outcomes than did children
      with other TBIs 1 year after injury. However, outcomes for these children were
      better than those reported previously. Many families caring for children after
      severe TBI are socially disadvantaged. Interventions to improve child outcomes
      may include enhanced family support.

PMID- 16452350
TI  - Identification of inflicted traumatic brain injury in well-appearing infants
      using serum and cerebrospinal markers: a possible screening tool.
AB  - OBJECTIVE: Inflicted traumatic brain injury (iTBI) is the leading cause of death
      from TBI in infants. Misdiagnosis of iTBI is common and results in increased
      morbidity and mortality. Biomarkers may be able to assist in screening infants
      who are at high risk for iTBI and whose injury might otherwise be missed. We
      investigated whether serum and/or cerebrospinal fluid (CSF) concentrations of
      neuron-specific enolase (NSE), S100B, and myelin-basic protein (MBP) are
      sensitive and specific for iTBI in high-risk infants. METHODS: A prospective case
      control study was conducted of 98 well-appearing infants who presented with
      nonspecific symptoms and no history of trauma. Serum or CSF was collected. NSE,
      S100B, and MBP concentrations were measured by enzyme-linked immunosorbent assay.
      Abnormal marker concentrations were defined a priori. Patients were followed for
      12 months to assess for subsequent abuse. RESULTS: Fourteen patients received a
      clinical diagnosis of iTBI. Using preestablished cutoffs, NSE was 77% sensitive
      and 66% specific and MBP was 36% sensitive and 100% specific for iTBI. S100B was
      neither sensitive nor specific for iTBI. Five patients who were not identified
      with iTBI at enrollment were identified at follow-up as being possible victims of
      abuse; 4 had an increased NSE concentration at enrollment. CONCLUSIONS: Serum
      and/or CSF concentrations of NSE and MBP may be useful as a screening test to
      identify infants who are at increased risk for iTBI and may benefit from
      additional evaluation with a head computed tomography scan. S100B is neither
      sensitive nor specific for iTBI in this study population. The ability to identify
      iTBI that might otherwise be missed has important implications for decreasing the
      morbidity and the mortality from iTBI.

PMID- 16452351
TI  - Cerebral oxygenation and electrical activity after birth asphyxia: their relation
      to outcome.
AB  - OBJECTIVE: To determine the value of regional cerebral oxygen saturation (rSo2),
      fractional cerebral tissue oxygen extraction (FTOE) measured by near-infrared
      spectroscopy (NIRS), and amplitude integrated electroencephalogram (aEEG) after
      birth asphyxia in relation to neurodevelopmental outcome. METHODS: NIRS measured
      rSo2, FTOE, and aEEG were monitored simultaneously, together with arterial oxygen
      saturation (Sao2) and blood pressure during the first 48 hours after severe birth
      asphyxia in 18 term infants. FTOE was calculated as [Sao2-rSo2]/Sao2.
      Neurodevelopmental outcome was assessed at 3, 9, and 18 months and 3 and 5 years
      of age. At the time points 6, 12, 18, 24, 30, 36, 42, and 48 hours after birth,
      the mean values of Sao2, rSo2, FTOE, and mean arterial blood pressure were
      calculated over a 1-hour period. A stepwise-regression model was used to
      investigate the relative contribution of rSo2, FTOE, or aEEG to developmental
      outcome. RESULTS: Nine Infants died during the neonatal period as a result of
      neurologic deterioration, and 8 infants had a normal outcome at 5 years of age.
      One child developed learning disabilities and a mild diplegia. The rSo2 and FTOE
      remained stable in infants with a normal outcome. The rSo2 increased and the FTOE
      decreased after 24 hours in the infants with an adverse outcome. (rSo2: 65% vs
      84% at 12 and 48 hours, respectively; FTOE: 0.32 vs 0.12 at 12 and 48 hours,
      respectively). aEEG showed the closest relationship with outcome, but also rSo2
      showed a significant correlation 24 hours after birth. CONCLUSIONS: rSo2 and FTOE
      seem to reflect secondary energy failure. aEEG showed the closest relationship
      with outcome after severe birth asphyxia.

PMID- 16452352
TI  - Persistent bacteremia and severe thrombocytopenia caused by coagulase-negative
      Staphylococcus in a neonatal intensive care unit.
AB  - OBJECTIVE: Coagulase-negative Staphylococcus (CoNS) is the most frequent cause of
      late-onset sepsis in NICUs, but mortality is rare and morbidity is unusual. We
      report a new syndrome of CoNS sepsis characterized by significant morbidity and
      persistent bacteremia despite aggressive antibiotic therapy and no identified
      focus of infection. METHODS: We conducted a retrospective review of infants in
      the NICU with CoNS bacteremia between 2000 and 2002. Statistical analysis
      included an initial exploratory analysis followed by logistic regression.
      Microbiological identification of all isolates and molecular typing were
      performed. RESULTS: Thirty-one neonates with persistent CoNS bacteremia were
      compared with 60 randomly selected neonates from a group of 140 with
      nonpersistent CoNS bacteremia. The clinical manifestations at presentation,
      gestational ages, and birth weights were similar in the 2 groups.
      Thrombocytopenia was present in 26 (84%) neonates with persistent CoNS bacteremia
      but only in 8 (13%) neonates in the nonpersistent group. Central venous
      catheterization increased the risk for persistent CoNS bacteremia, but 42% of the
      persistent group was never catheterized. Staphylococcus epidermidis was the most
      common isolate in both groups. Molecular typing failed to identify a predominant
      clone. CONCLUSIONS: The syndrome of persistent CoNS septicemia is remarkable for
      thrombocytopenia and persistence in the absence of central venous
      catheterization. Clinical manifestations at presentation and demographic
      characteristics did not discriminate between the persistent and nonpersistent
      groups. We did not identify the emergence of a particularly virulent clone, but
      it is possible that some strains of CoNS have acquired the capacity to persist
      under different conditions.

PMID- 16452353
TI  - Effect of altitude on hospitalizations for respiratory syncytial virus infection.
AB  - OBJECTIVE: Respiratory syncytial virus (RSV) infection is the foremost cause of
      serious lower respiratory tract infection in young children and infants. Because
      higher rates of hospitalization for bronchiolitis and pneumonia have been noted
      in high-altitude regions, we hypothesized that physiologic responses to altitude
      would predispose children to more severe illness from RSV infection. This study
      examined the effect of residential altitude on hospitalizations for RSV infection
      in Colorado from 1998 through 2002. METHODS: A geographic information system was
      used to assemble data for altitude and demographic variables by zip code
      tabulation areas. Data then were linked with hospital discharge data for RSV
      infections. Poisson regression models were developed to explore correlations
      between hospitalization rates and residential altitude, after adjustment for
      socioeconomic differences in the underlying population. RESULTS: RSV-associated
      hospitalizations averaged 15.9 per 1000 infants who were younger than 1 year and
      1.8 per 1000 children who were 1 to 4 years of age per season. A multivariate
      analysis suggested that the rate of hospitalization for RSV-specific
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes increased 25% among infants who were younger than 1 year and 53% among
      children who were 1 to 4 years of age for every 1000-m increase in altitude. The
      risk for RSV-associated hospitalization was highest at elevations above 2500 m.
      CONCLUSIONS: High altitude above 2500 m is a modest predictor for RSV-associated
      hospitalization. Practitioners in these regions should consider additional
      efforts to educate parents about RSV infection and its prevention and the
      importance of early treatment.

PMID- 16452354
TI  - Factors associated with neurodevelopmental outcome at 2 years after very preterm
      birth: the population-based Nord-Pas-de-Calais EPIPAGE cohort.
AB  - OBJECTIVE: We sought to (1) evaluate at 2 years the postsurfactant era
      developmental outcome of children who were born before 33 weeks of gestational
      age (GA) in the Nord-Pas-de-Calais area in France in 1997 and (2) identify risk
      factors of poor developmental quotient (DQ). Children were part of the EPIPAGE
      study, which included all of these births in 9 French regions. METHODS: A
      prospective observational study was conducted of all births before 33 weeks in
      1997. Risk factors of poor DQ were obtained from a multiple linear regression,
      and results were expressed as DQ differences with 95% confidence intervals.
      RESULTS: A total of 546 births were included in the study. A total of 461 (84.4%)
      had a clinical evaluation at 2 years of age, and 380 (69.6%) had an assessment
      with the use of the Brunet-Lezine scale of infant development. Their mean GA was
      29.9 weeks (29.7-30.1 weeks), and mean birth weight was 1378 g (1338-1418 g). A
      total of 9% had a recognizable pattern of cerebral palsy, 0.2% were blind, and
      0.8% required hearing aids. The mean DQ was 94 +/- 11 and decreased from 97 at 32
      weeks to 86 at 24 to 25 weeks. After multivariate analysis, children who were
      born at 24 to 25 weeks had a mean DQ reduction of 11 points (-20 to -1) compared
      with those who were born at 32 weeks, but minor differences were found from 26 to
      32 weeks. Boys had a DQ 4 points lower than girls (-7 to -1). CONCLUSION: In this
      study, the outcome of extremely preterm infants was poor. After 25 weeks, outcome
      was related mainly to the sociocultural level of the family and to the presence
      of severe cerebral ultrasound abnormalities. Consequently, in the postsurfactant
      era, we have to propose follow-up programs to children who are born extremely
      preterm and to concentrate our efforts on children with less-than-optimal social
      and family setting.

PMID- 16452356
TI  - Axial and radial diffusivity in preterm infants who have diffuse white matter
      changes on magnetic resonance imaging at term-equivalent age.
AB  - OBJECTIVE: Diffuse excessive high signal intensity (DEHSI) is observed in the
      majority of preterm infants at term-equivalent age on conventional MRI, and
      diffusion-weighted imaging has shown that apparent diffusion coefficient values
      are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion
      tensor imaging on preterm infants at term-equivalent age and term control infants
      to test the hypothesis that radial diffusivity was significantly different in the
      WM in preterm infants with DEHSI compared with both preterm infants with normal
      appearing WM on conventional MRI and term control infants. METHODS: Diffusion
      tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8
      term control infants. Values for axial (lambda1) and radial [(lambda2 +
      lambda3)/2] diffusivity were calculated in regions of interest positioned in the
      central WM at the level of the centrum semiovale, frontal WM, posterior
      periventricular WM, occipital WM, anterior and posterior portions of the
      posterior limb of the internal capsule, and the genu and splenium of the corpus
      callosum. RESULTS: Radial diffusivity was elevated significantly in the posterior
      portion of the posterior limb of the internal capsule and the splenium of the
      corpus callosum, and both axial and radial diffusivity were elevated
      significantly in the WM at the level of the centrum semiovale, the frontal WM,
      the periventricular WM, and the occipital WM in preterm infants with DEHSI
      compared with preterm infants with normal-appearing WM and term control infants.
      There was no significant difference between term control infants and preterm
      infants with normal-appearing WM in any region studied. CONCLUSIONS: These
      findings suggest that DEHSI represents an oligodendrocyte and/or axonal
      abnormality that is widespread throughout the cerebral WM.

PMID- 16452355
TI  - A double-blind, randomized, controlled study of a "stress dose" of hydrocortisone
      for rescue treatment of refractory hypotension in preterm infants.
AB  - OBJECTIVE: To assess the effectiveness of a "stress dose" of hydrocortisone for
      rescue treatment of refractory hypotension and adrenocortical insufficiency of
      prematurity in very low birth weight (VLBW) infants. We hypothesized that
      significantly more VLBW infants who were receiving dopamine > or =10 microg/kg
      per min could wean off vasopressor support 72 hours after treatment with
      hydrocortisone. METHODS: A double-blind, randomized, controlled study was
      conducted in a university neonatal center. Forty-eight VLBW infants who had
      refractory hypotension and required dopamine > or =10 microg/kg per min were
      randomly assigned to receive a stress dose of hydrocortisone (1 mg/kg every 8
      hours for 5 days; n = 24) or an equivalent volume of the placebo solution
      (isotonic saline; n = 24). RESULTS: The baseline clinical characteristics were
      similar between the groups. Serum cortisol concentrations were very low
      immediately before randomization in both groups of infants. Significantly more
      VLBW infants who were treated with hydrocortisone weaned off vasopressor support
      72 hours after starting treatment. The use of volume expander, cumulative dose of
      dopamine, and dobutamine were significantly less in hydrocortisone-treated
      infants compared with control infants. In addition, the median duration of
      vasopressor treatment was halved in hydrocortisone-treated patients. Two versus
      11 infants in the hydrocortisone and control groups required a second vasopressor
      for treatment of refractory hypotension. The trend (linear and quadratic) of the
      mean arterial blood pressure was also significantly and consistently higher in
      hydrocortisone-treated infants. CONCLUSIONS: A stress dose of hydrocortisone was
      effective in treating refractory hypotension in VLBW infants. Although routine
      and prophylactic use of systemic corticosteroids could not be recommended because
      of their potential adverse effects, this relatively low dose of hydrocortisone
      would probably be preferable to high-dose dexamethasone for treatment of
      refractory hypotension in emergency and life-threatening situations.

PMID- 16452357
TI  - Vaccine adverse event reporting system reporting source: a possible source of
      bias in longitudinal studies.
AB  - OBJECTIVE: The US Vaccine Adverse Event Reporting System (VAERS) is a passive
      reporting system to which anyone can report an event. Publicity related to
      potential adverse events may change reporting patterns. The objective of this
      paper is to show how litigation-related reports have influenced the trends in
      possible adverse event reports to VAERS. METHODS: The VAERS public-use data files
      were downloaded in July 2004 and translated into identical SAS data sets for
      analysis. Cases that were related to litigation were identified using a word
      search algorithm. All cases for the most frequently reported symptoms in
      litigation (overdose, neuropathy, autism, "mental retardation," arthralgia, and
      "speech disorder") were reviewed. RESULTS: In recent years, most case reports to
      VAERS that were related to overdose, neuropathy, and thimerosal were related to
      litigation. Many cases that were related to autism and mental retardation were as
      well. CONCLUSIONS: This review shows a previously undisclosed rise in the number
      of reports to the VAERS related to pending litigation for vaccine injury. The
      implications of this for understanding longitudinal reporting patterns are
      discussed.

PMID- 16452358
TI  - Temporal associations among energy intake, plasma linoleic acid, and growth
      improvement in response to treatment initiation after diagnosis of cystic
      fibrosis.
AB  - OBJECTIVE: It is unclear why some patients with cystic fibrosis (CF) succeed
      ("responders") in recovering from malnutrition and growth faltering after
      treatment initiation whereas others fail to do so ("nonresponders"). We conducted
      a study to test the hypothesis that sustained high energy intake (increased EN)
      and normal plasma essential fatty acid status are critical determinants of
      treatment responsiveness within 2 years after diagnosis of CF. METHODS: A total
      of 71 CF children who had pancreatic insufficiency but not meconium ileus and
      were enrolled in the Wisconsin CF Neonatal Screening Project were studied.
      Responders were defined by having achieved adequate weight gain, as indicated by
      a recovery of weight z score (Wtz) comparable to Wtz at birth (WtzBR) within 2
      years of diagnosis. Increased EN and sustained normal plasma linoleic acid level
      (increased pLA) were defined by achieving energy intake > or =120% of estimated
      requirement for > or =75% of the time and maintaining plasma LA > or =26% of
      total fatty acids for > or =75% of the time, respectively. RESULTS: Thirty-two
      (68%) screened patients and 13 (54%) patients whose CF was diagnosed
      conventionally recovered WtzBR within 2 years of diagnosis. Screened patients
      responded at significantly younger ages (mean/median: 6.3/4.3 months) than
      patients whose CF was diagnosed conventionally (mean/median: 15.8/11.8 months).
      Proportionately fewer screened patients (33%) achieved increased EN compared with
      patients whose CF was diagnosed conventionally (73%). However, more screened
      patients responded to increased EN and recovered WtzBR (91%) than patients whose
      CF was diagnosed conventionally (56%), although this difference was of borderline
      significance. Compared with having neither increased EN nor increased pLA, the
      likelihood of being a responder was greatest with combined increased EN and
      increased pLA, followed by increased EN only. The positive associations between
      increased EN and increased pLA to treatment responsiveness remained significant
      after adjustment for neonatal screening status, baseline height and weight
      status, and indices of pulmonary disease severity. CONCLUSION: Increased EN and
      increased pLA are critical in promoting adequate weight gain in children with
      newly diagnosed CF.

PMID- 16452359
TI  - Timing of solid food introduction in relation to atopic dermatitis and atopic
      sensitization: results from a prospective birth cohort study.
AB  - OBJECTIVE: Prophylactic feeding guidelines recommend a delayed introduction of
      solid foods for the prevention of atopic diseases. Scientific evidence for this
      is scarce. This study investigates whether a delayed introduction of solids (past
      4 months or 6 months) is protective against the development of atopic dermatitis
      (AD) and atopic sensitization when considering reverse causality. METHODS: Data
      from 2612 infants in an ongoing birth cohort study were analyzed at 2 years of
      age. Information on diet and on symptoms and diagnoses of AD was collected
      semiannually, and information on specific immunoglobulin E levels was collected
      at 2 years of age. RESULTS: Solid food introduction past the first 4 months of
      life decreased the odds of symptomatic AD but not for doctor-diagnosed AD,
      combined doctor-diagnosed and symptomatic AD, or atopic sensitization. Postponing
      the introduction beyond the sixth month of life was not protective in relation to
      either definition of AD or atopic sensitization. There was also no evidence for a
      protective effect of a delayed introduction of solids on AD and atopic
      sensitization in children of atopic parents. There was clear evidence for reverse
      causality between early skin or allergic symptoms and the introduction of solids.
      CONCLUSIONS: This study does not find evidence supporting a delayed introduction
      of solids beyond the sixth month of life for the prevention of AD and atopic
      sensitization. We cannot rule out that delaying the introduction of solids for
      the first 4 months of life might offer some protection. Measures to avoid reverse
      causality have to be considered in the conduction, analysis, and interpretation
      of cohort studies on the topic.

PMID- 16452360
TI  - Neck/shoulder, low back, and arm pain in relation to computer use, physical
      activity, stress, and depression among Dutch adolescents.
AB  - OBJECTIVE: To examine among adolescents (1) the prevalence of neck/shoulder, low
      back, and arm pain within different sociodemographic groups and (2) the
      association of neck/shoulder, low back, and arm pain with computer use, physical
      activity, depression, and stress. METHODS: A school-based questionnaire survey in
      2002 and 2003 of neck/shoulder, low back, and arm pain, computer use, physical
      activity, depression, and stress. The survey was given to 3485 adolescents aged
      12 to 16 years who attended secondary schools in Amsterdam, Netherlands. RESULTS:
      The overall prevalence of neck/shoulder, low back, and arm pain was 11.5%, 7.5%,
      and 3.9%, respectively. The prevalence of neck/shoulder pain was higher among
      girls and adolescents not living with both parents. The prevalence of low back
      pain also was higher among girls. Depressive symptoms were associated with
      neck/shoulder pain, low back pain, and arm pain. The stress experienced was
      associated with neck/shoulder pain and with low back pain. CONCLUSIONS: This
      study strengthens the findings that musculoskeletal pain is common among
      adolescents and is associated with depression and stress but not with computer
      use and physical activity.

PMID- 16452361
TI  - Inequality in the built environment underlies key health disparities in physical
      activity and obesity.
AB  - CONTEXT: Environmental factors are suggested to play a major role in physical
      activity (PA) and other obesity-related behaviors, yet there is no national
      research on the relationship between disparity in access to recreational
      facilities and additional impact on PA and overweight patterns in US adolescents.
      OBJECTIVE: In a nationally representative cohort, we sought to assess the
      geographic and social distribution of PA facilities and how disparity in access
      might underlie population-level PA and overweight patterns. DESIGN, SETTING, AND
      PARTICIPANTS: Residential locations of US adolescents in wave I (1994-1995) of
      the National Longitudinal Study of Adolescent Health (N = 20745) were geocoded,
      and a 8.05-km buffer around each residence was drawn (N = 42857 census-block
      groups [19% of US block groups]). PA facilities, measured by national databases
      and satellite data, were linked with Geographic Information Systems technology to
      each respondent. Logistic-regression analyses tested the relationship of PA
      related facilities with block-group socioeconomic status (SES) (at the community
      level) and the subsequent association of facilities with overweight and PA (at
      the individual level), controlling for population density. MAIN OUTCOME MEASURES:
      Outcome measures were overweight (BMI > or = 95th percentile of the Centers for
      Disease Control and Prevention/National Center for Health Statistics growth
      curves) and achievement of > or = 5 bouts per week of moderate-vigorous PA.
      RESULTS: Higher-SES block groups had a significantly greater relative odds of
      having 1 or more facilities. Low-SES and high-minority block groups were less
      likely to have facilities. Relative to zero facilities per block group, an
      increasing number of facilities was associated with decreased overweight and
      increased relative odds of achieving > or = 5 bouts per week of moderate-vigorous
      PA. CONCLUSIONS: Lower-SES and high-minority block groups had reduced access to
      facilities, which in turn was associated with decreased PA and increased
      overweight. Inequality in availability of PA facilities may contribute to ethnic
      and SES disparities in PA and overweight patterns.

PMID- 16452362
TI  - Full breastfeeding duration and associated decrease in respiratory tract
      infection in US children.
AB  - OBJECTIVE: The American Academy of Pediatrics recommends exclusive breastfeeding
      for an infant's first 6 months of life. When compared with exclusive
      breastfeeding for 4 months, greater protection against gastrointestinal
      infection, but not respiratory tract infection, has been demonstrated for the 6
      month duration. The objective of this study was to ascertain if full
      breastfeeding of > or = 6 months compared with 4 to < 6 months in the United
      States provides greater protection against respiratory tract infection. METHODS:
      Secondary analysis of data from the National Health and Nutrition Examination
      Survey III, a nationally representative cross-sectional home survey conducted
      from 1988 to 1994, was performed. Data from 2277 children aged 6 to < 24 months,
      who were divided into 5 groups according to breastfeeding status, were compared.
      Children who required neonatal intensive care were excluded. SUDAAN software was
      used to account for the complex sampling design. Logistic regression adjusted for
      confounding factors. Outcome measures included adjusted odds of acquiring
      pneumonia, > or = 3 episodes of cold/influenza, > or = 3 episodes of otitis media
      (OM), or wheezing in the past year or acquiring first OM at < 12 months of age.
      RESULTS: In unadjusted analyses, infants who were fully breastfed for 4 to < 6
      months (n = 223) were at greater risk for pneumonia than those who were fully
      breastfed for > or = 6 months (n = 136) (6.5% vs 1.6%). There were not
      statistically significant differences in > or = 3 episodes of cold/influenza (45%
      vs 41%), wheezing (23% vs 24%), > or = 3 episodes of OM (27% vs 20%), or first OM
      at < 12 months of age (49% vs 47%). Adjusting for demographic variables,
      childcare, and smoke exposure revealed statistically significant increased risk
      for both pneumonia (odds ratio [OR]: 4.27; 95% confidence interval [CI]: 1.27
      14.35) and > or = 3 episodes of OM (OR: 1.95; 95% CI: 1.06-3.59) in those who
      were fully breastfed for 4 to < 6 months compared with > or = 6 months.
      CONCLUSIONS: This nationally representative study documents increased risk of
      respiratory tract infection including pneumonia and recurrent OM in children who
      were fully breastfed for 4 vs 6 months. These findings support current
      recommendations that infants receive only breast milk for the first 6 months of
      life.

PMID- 16452363
TI  - Panton-Valentine leukocidin genes are associated with enhanced inflammatory
      response and local disease in acute hematogenous Staphylococcus aureus
      osteomyelitis in children.
AB  - BACKGROUND: Staphylococcus aureus strains carrying the genes encoding Panton
      Valentine leukocidin (pvl-positive [pvl+]) are associated with more febrile days
      and higher complication rates of osteomyelitis in children than are pvl-negative
      (pvl-) strains. OBJECTIVES: Selected clinical, laboratory, and radiographic
      findings in children with osteomyelitis caused by pvl+ and pvl- S aureus strains
      were compared. METHODS: The demographics, selected clinical features, laboratory
      values, and radiographic findings of children with community-acquired S aureus
      osteomyelitis prospectively identified at Texas Children's Hospital between
      August 2001 and July 2004 were reviewed. Polymerase chain reaction was performed
      to detect the genes for pvl (luk-S-PV and luk-F-PV) and fibronectin-binding
      protein (fnbB) in S aureus isolates. Chi2, 2-sample t test, and multiple logistic
      regression were used for statistical analysis. RESULTS: Methicillin-susceptible
      and methicillin-resistant S aureus (MSSA and MRSA, respectively) caused
      osteomyelitis in 33 and 56 children, respectively. Twenty-six isolates were pvl-
      (26 MSSA), 59 were pvl+ (3 MSSA, 56 MRSA), and 4 were not available for analysis
      (4 MSSA). On univariate analysis, patients with pvl+ S aureus isolates had
      significantly higher erythrocyte sedimentation rate (ESR) and C-reactive protein
      (CRP) level both at presentation and as a maximum value during hospitalization
      and were more likely to have a blood culture positive for S aureus during their
      admission. Patients with pvl+ S aureus isolates were significantly more likely to
      have concomitant myositis or pyomyositis compared with patients with pvl- S
      aureus isolates on MRI. In a multivariate analysis pvl remained significantly
      associated with ESR and CRP levels at presentation and blood culture positive for
      S aureus. pvl+ status and younger age were associated with myositis on MRI.
      CONCLUSIONS: Osteomyelitis caused by pvl+ S aureus strains were associated with
      more severe local disease and a greater systemic inflammatory response compared
      with osteomyelitis caused by pvl- S aureus.

PMID- 16452364
TI  - Parental expectations, physical punishment, and violence among adolescents who
      score positive on a psychosocial screening test in primary care.
AB  - OBJECTIVE: We sought to examine the relationship between perceived and stated
      parental expectations regarding adolescents' use of violence, parental use of
      physical punishment as discipline, and young adolescents' violence-related
      attitudes and involvement. METHODS: Surveys were completed by 134 youth and their
      parents attending 8 pediatric practices. All youth were 10 to 15 years of age and
      had scored positive on a psychosocial screening test. RESULTS: Multivariate
      analyses revealed that perceived parental disapproval of the use of violence was
      associated with a more prosocial attitude toward interpersonal peer violence and
      a decreased likelihood of physical fighting by the youth. Parental report of
      whether they would advise their child to use violence in a conflict situation
      (stated parental expectations) was not associated with the adolescents' attitudes
      toward interpersonal peer violence, intentions to fight, physical fighting,
      bullying, or violence victimization. Parental use of corporal punishment as a
      disciplining method was inversely associated with a prosocial attitude toward
      interpersonal peer violence among the youth and positively correlated with
      youths' intentions to fight and fighting, bullying, and violence victimization.
      CONCLUSIONS: Perceived parental disapproval of the use of violence may be an
      important protective factor against youth involvement in violence, and parental
      use of physical punishment is associated with both violence perpetration and
      victimization among youth. Parents should be encouraged to clearly communicate to
      their children how to resolve conflicts without resorting to violence and to
      model these skills themselves by avoiding the use of physical punishment.

PMID- 16452365
TI  - Onset of mechanical ventilation is associated with rapid activation of
      circulating phagocytes in preterm infants.
AB  - OBJECTIVE: In preterm infants with respiratory distress syndrome (RDS),
      circulating neutrophils are activated. Kinetics and effects of surfactant therapy
      on this activation are unknown. Therefore, we studied activation of circulating
      neutrophils and monocytes in newborn preterm infants with and without RDS.
      PATIENTS AND METHODS: Preterm infants with RDS who were mechanically ventilated
      and received surfactant ("ventilated infants": n = 38; mean gestational age +/-
      SD: 28.3 +/- 2.2 weeks; mean birth weight +/- SD: 1086 +/- 353 g) and preterm
      infants who received nasal continuous positive airway pressure (n = 8) or no
      ventilatory support (n = 17) ("control infants": mean gestational age +/- SD:
      32.1 +/- 1.2 weeks; mean birth weight +/- SD: 1787 +/- 457 g) were recruited.
      Blood samples were taken from ventilated infants at birth, before surfactant
      treatment, at 1 and 2 hours after surfactant, and at 12 to 24 hours of age. Blood
      samples were taken from control infants at birth, at 2 to 6 hours, and at 12 to
      24 hours of age. Phagocyte CD11b expression was analyzed by flow cytometry.
      RESULTS: In ventilated infants, phagocyte CD11b expression increased from birth
      to the first postnatal samples. It increased further by 12 to 24 hours of age.
      Control infants with or without nasal continuous positive airway pressure showed
      no significant increase after birth. At 12 to 24 hours of age, phagocyte CD11b
      expression was higher in ventilated infants than in control infants. In
      ventilated infants, neutrophil CD11b expression at 1 and 2 hours after surfactant
      correlated positively with gestational age. CONCLUSIONS: In preterm infants with
      RDS, significant activation of circulating phagocytes occurs within 1 to 3 hours
      of the onset of mechanical ventilation, independent of surfactant administration,
      which indicates that mechanical ventilation may be the inducer of this systemic
      inflammatory response.

PMID- 16452366
TI  - Anticipatory guidance and violence prevention: results from family and
      pediatrician focus groups.
AB  - OBJECTIVES: Anticipatory guidance is a cornerstone of modern pediatric practice.
      Recent American Academy of Pediatrics policies related to violence prevention,
      notably those that advocate firearms safety and the use of alternatives to
      corporal punishment, seem to be discrepant with common parenting practices. To
      develop more effective anticipatory guidance, we sought the opinions of parents
      and pediatricians on how best to communicate these messages. DESIGN: Focus groups
      were conducted to elicit parent and provider opinions. SUBJECTS: Forty-nine
      parents participated in a total of 9 90-minute focus groups that were held in 3
      cities. Twenty-six pediatricians participated in 3 focus groups that were held at
      a single national meeting. PROCEDURES: Participants were read summaries of
      current American Academy of Pediatrics policies and led through a systematic
      discussion of how these policies might best be communicated. The group
      discussions were audiotaped, transcribed, and analyzed. Common themes heard in
      multiple groups are reported. RESULTS: Parents provided specific feedback about
      corporal punishment and firearms and also raised a number of general issues.
      Pediatricians reported that anticipatory guidance was important to them but cited
      cultural and reimbursement issues as barriers to practice. They also reported the
      need for additional training and support to make anticipatory guidance more
      effective. DISCUSSION: Focus groups provide insight into doctor-patient
      communications and can inform efforts to improve primary prevention in the
      clinical setting. Anticipatory guidance that consists of authoritative useful
      information, offered in a supportive manner that communicates respect for
      parental decision-making, may be effective in improving parenting practices.

PMID- 16452367
TI  - Household food insecurity and overweight status in young school children: results
      from the Early Childhood Longitudinal Study.
AB  - OBJECTIVE: Recent work on the determinants of obesity has shown a positive
      association between household food insecurity and overweight status in adult
      women, yet research exploring this issue in children has been inconclusive. In
      this study we examine the association between food insecurity and overweight
      status in young school children by using a large, nationally representative
      sample. METHODS: Data from the Early Childhood Longitudinal Study-Kindergarten
      Cohort (ECLS-K) were analyzed. Replicate heights and weights were measured on
      kindergarten children (N = 16889) in the spring of 1999. Children with a body
      mass index > or = 95th percentile of their gender-specific BMI-for-age chart were
      considered overweight. Food-insecurity status was assessed by using the full 18
      question US Department of Agriculture Household Food Security Scale. Multivariate
      logistic regression was used to assess the relationship between overweight and
      food-insecurity status while controlling for potential demographic,
      socioeconomic, and behavioral confounders. RESULTS: Overall, 11.2% of the girls
      and 11.8% of the boys were overweight. Children from food-insecure households
      were 20% less likely to be overweight than their food-secure counterparts.
      Similar results on the food-insecurity/overweight link were found across a range
      of different models and expressions for key variables. Positive predictors of
      overweight status included low physical activity, television watching for > 2
      hours/day, high birth weight, black or Latino ethnicity, and low income.
      CONCLUSIONS: There are strong arguments for reducing food insecurity among
      households with young children. This research suggests that these arguments would
      be based on reasons other than a potential link to obesity. Low activity levels
      and excessive television watching, however, were strongly related to overweight
      status, a finding that supports continued efforts to intervene in these areas.

PMID- 16452368
TI  - Toward understanding kernicterus: a challenge to improve the management of
      jaundiced newborns.
AB  - PURPOSE: We sought to evaluate the sensitivity and specificity of total serum
      bilirubin concentration (TSB) and free (unbound) bilirubin concentration (Bf) as
      predictors of risk for bilirubin toxicity and kernicterus and to examine
      consistency between these findings and proposed mechanisms of bilirubin transport
      and brain uptake. METHODS: A review of literature was undertaken to define basic
      principles of bilirubin transport and brain uptake leading to neurotoxicity. We
      then reviewed experimental and clinical evidence that relate TSB or Bf to risk
      for bilirubin toxicity and kernicterus. RESULTS: There are insufficient published
      data to precisely define sensitivity and specificity of either TSB or Bf in
      determining risk for acute bilirubin neurotoxicity or chronic sequelae
      (kernicterus). However, available laboratory and clinical evidence indicate that
      Bf is better than TSB in discriminating risk for bilirubin toxicity in patients
      with severe hyperbilirubinemia. These findings are consistent with basic
      pharmacokinetic principles involved in bilirubin transport and tissue uptake.
      CONCLUSIONS: Experimental and clinical data strongly suggest that measurement of
      Bf in newborns with hyperbilirubinemia will improve risk assessment for
      neurotoxicity, which emphasizes the need for additional clinical evaluation
      relating Bf and TSB to acute bilirubin toxicity and long-term outcome. We
      speculate that establishing risk thresholds for neurotoxicity by using newer
      methods for measuring Bf in minimally diluted serum samples will improve the
      sensitivity and specificity of serum indicators for treating hyperbilirubinemia,
      thus reducing unnecessary aggressive intervention and associated cost and
      morbidity.

PMID- 16452369
TI  - Improved asthma care after enrollment in the State Children's Health Insurance
      Program in New York.
AB  - BACKGROUND: Uninsured children with asthma are known to face barriers to asthma
      care, but little is known about the impact of health insurance on asthma care.
      OBJECTIVES: We sought to assess the impact of New York's State Children's Health
      Insurance Program (SCHIP) on health care for children with asthma. DESIGN:
      Parents of a stratified random sample of new enrollees in New York's SCHIP were
      interviewed by telephone shortly after enrollment (baseline, n = 2644 [74% of
      eligible children]) and 1 year later (follow-up, n = 2310 [87%]). Asthma was
      defined by parent report using questions based on National Heart, Lung, and Blood
      Institute criteria. A comparison group (n = 401) who enrolled in SCHIP 1 year
      later was interviewed as a test for secular trends. MAIN OUTCOME MEASURES: Access
      (having a usual source of care [USC], unmet health needs, problems receiving
      acute asthma care), asthma-related medical visits, quality (continuity of care at
      the USC, problems receiving chronic asthma care, use of antiinflammatory
      medications), and asthma outcomes (change in asthma care or severity) were the
      main outcome measures used. Bivariate and multivariate analyses compared measures
      at baseline (year before SCHIP) versus follow-up (year during SCHIP). RESULTS:
      Three-hundred eighty-three children (14%) had asthma at baseline, and 364 had
      asthma at follow-up (16%). No secular trends were detected between the baseline
      study group and the comparison group. After enrollment in SCHIP, improvements
      were noted in access: lacking a USC (decrease from 5% to 1%), unmet health needs
      (48% to 21%), and problems getting to the USC for asthma (13 to 4%). Children had
      fewer asthma-related attacks and medical visits after SCHIP (mean number of
      attacks: 9.5 to 3.8: mean number of asthma visits: 3.0 to 1.5; hospitalizations:
      11% to 3%). Quality of asthma care improved for general measures (most/all visits
      to USC: 53% to 94%; mean rating of provider: 7.9 to 8.8 of 10) and asthma
      specific measures (problems getting to the USC for asthma care when child was
      well: 13% to 1%). More than two thirds of the parents at follow-up reported that
      both quality of asthma care and asthma severity were "better or much better" than
      at baseline, generally because of insurance coverage or lower costs of
      medications and medical care. CONCLUSIONS: Enrollment in New York's SCHIP was
      associated with improvements in access to asthma care, quality of asthma care,
      and asthma-specific outcomes. These findings suggest that health insurance
      improves the health of children with asthma.

PMID- 16452370
TI  - Screening for speech and language delay in preschool children: recommendation
      statement.

PMID- 16452371
TI  - Hydrocortisone and vasopressor-resistant shock in preterm neonates.

PMID- 16452372
TI  - Pediatricians leading the way: integrating a career and a family/personal life
      over the life cycle.

PMID- 16452373
TI  - Bilirubin unbound: deja vu all over again?

PMID- 16452374
TI  - Unbound bilirubin and risk assessment in the jaundiced newborn: possibilities and
      limitations.

PMID- 16452375
TI  - Children presenting with complex febrile seizures do not routinely need computed
      tomography scanning in the emergency department.

PMID- 16452376
TI  - Association of H2-blocker therapy and higher incidence of necrotizing
      enterocolitis: a case of excessive collateral damage?

PMID- 16452377
TI  - Screening for speech and language delay in preschool children: more answers are
      needed.

PMID- 16452378
TI  - Toddlers at risk for paper shredder injury in the home: easy access and severe
      injury.
AB  - A 2-year-old girl sustained severe injury to 2 fingers from a home paper
      shredder. This case illustrates the risk of injury from paper shredders, which
      are increasingly common household items. Toddlers are at risk of finger injury
      and amputation. The US Consumer Product Safety Commission performed an
      investigation of reported injuries and the characteristics of paper shredders
      that might have contributed to the injuries, and we summarize their findings.

PMID- 16452379
TI  - Successful wireless capsule endoscopy for a 2.5-year-old child: obscure
      gastrointestinal bleeding from mixed, juvenile, capillary hemangioma-angiomatosis
      of the jejunum.
AB  - The lesion responsible for obscure gastrointestinal bleeding in the pediatric
      population may not be determined with standard primary endoscopic methods.
      Wireless capsule endoscopy, now a first-line modality for evaluation of the small
      bowel in the adult population, is a tool that may be useful among children. We
      report a case of a 2.5-year-old girl who presented with melenic stools. Upper and
      lower endoscopy, Meckel scans, and mesenteric angiography yielded negative
      results. Wireless capsule endoscopy identified numerous abnormal, dilated, blood
      vessels in the proximal jejunum, with associated fresh blood. The patient
      underwent surgical exploration, with resection of the affected portion of the
      jejunum. Pathologically, the dilated blood vessels were consistent with mixed,
      juvenile, capillary hemangioma-angiomatosis of developmental or congenital
      origin. The patient fared well postoperatively, with no additional bleeding in 9
      months of follow-up monitoring. This case report highlights the use of capsule
      endoscopy in the diagnosis and successful treatment of gastrointestinal bleeding
      in a young infant. This is the youngest reported patient treated with the use of
      wireless capsule endoscopy in the pediatric population.

PMID- 16452380
TI  - Dietary recommendations for children and adolescents: a guide for practitioners.
AB  - Since the American Heart Association last presented nutrition guidelines for
      children, significant changes have occurred in the prevalence of cardiovascular
      risk factors and nutrition behaviors in children. Overweight has increased,
      whereas saturated fat and cholesterol intake have decreased, at least as
      percentage of total caloric intake. Better understanding of children's
      cardiovascular risk status and current diet is available from national survey
      data. New research on the efficacy of diet intervention in children has been
      published. Also, increasing attention has been paid to the importance of
      nutrition early in life, including the fetal milieu. This scientific statement
      summarizes current available information on cardiovascular nutrition in children
      and makes recommendations for both primordial and primary prevention of
      cardiovascular disease beginning at a young age.

PMID- 16452381
TI  - The pediatrician and disaster preparedness.
AB  - Recent natural disasters and events of terrorism and war have heightened
      society's recognition of the need for emergency preparedness. In addition to the
      unique pediatric issues involved in general emergency preparedness, several
      additional issues related to terrorism preparedness must be considered, including
      the unique vulnerabilities of children to various agents as well as the limited
      availability of age- and weight-appropriate antidotes and treatments. Although
      children may respond more rapidly to therapeutic intervention, they are at the
      same time more susceptible to various agents and conditions and more likely to
      deteriorate if not monitored carefully. The challenge of dealing with the threat
      of terrorism, natural disasters, and public health emergencies in the United
      States is daunting not only for disaster planners but also for our medical system
      and health professionals of all types, including pediatricians. As part of the
      network of health responders, pediatricians need to be able to answer concerns of
      patients and families, recognize signs of possible exposure to a weapon of
      terror, understand first-line response to such attacks, and sufficiently
      participate in disaster planning to ensure that the unique needs of children are
      addressed satisfactorily in the overall process. Pediatricians play a central
      role in disaster and terrorism preparedness with families, children, and their
      communities. This applies not only to the general pediatrician but also to the
      pediatric medical subspecialist and pediatric surgical specialist. Families view
      pediatricians as their expert resource, and most of them expect the pediatrician
      to be knowledgeable in areas of concern. Providing expert guidance entails
      educating families in anticipation of events and responding to questions during
      and after actual events. It is essential that pediatricians educate themselves
      regarding these issues of emergency preparedness. For pediatricians, some
      information is currently available on virtually all of these issues in recently
      produced printed materials, at special conferences, in broadcasts of various
      types, and on the Internet. However, selecting appropriate, accurate sources of
      information and determining how much information is sufficient remain difficult
      challenges. Similarly, guidance is needed with respect to developing relevant
      curricula for medical students and postdoctoral clinical trainees.

PMID- 16452382
TI  - Reducing the risk of HIV infection associated with illicit drug use.
AB  - Substance abuse, specifically the use of illicit drugs that are administered
      intravenously, continues to play a role in the transmission of human
      immunodeficiency virus type 1 (HIV-1) among adolescents and young adults (youth).
      Risks of HIV-1 infection may result from direct exposure to contaminated blood
      through sharing of injection drug equipment and from unsafe sexual practices
      (while under the influence of drugs and/or in exchange for drugs). Reducing the
      risk of HIV-1 infection that is associated with illicit drug use requires
      prevention education and prompt engagement in treatment. Providing patients with
      education, instruction on decontamination of used injection drug equipment,
      improved access to sterile syringes and needles, and postexposure prophylaxis may
      decrease their risk of acquiring HIV-1 infection. Pediatricians should assess
      risk behaviors as part of every health care encounter, including queries about
      tobacco, alcohol, and marijuana use. The risks and benefits of postexposure
      prophylaxis with antiretroviral drugs should be considered for youth with a
      single recent (within 72 hours) high-risk exposure to HIV-1 through sharing
      needles/syringes with an HIV-1-infected individual or having unprotected
      intercourse with an individual who engages in injection drug use. Such
      prophylaxis must be accompanied by risk-reduction counseling, appropriate
      referrals for treatment, and evaluation for pregnancy and associated sexually
      transmitted infections. There is an urgent need for more substance-abuse
      prevention and treatment programs, legislation that facilitates unencumbered
      access to sterile syringes, and expedient availability of reproductive health
      care services for sexually active youth, including voluntary HIV-1 counseling and
      testing.

PMID- 16452383
TI  - Screening examination of premature infants for retinopathy of prematurity.
AB  - This statement revises a previous statement on screening of preterm infants for
      retinopathy of prematurity (ROP) that was published in 2001. ROP is a pathologic
      process that occurs only in immature retinal tissue and can progress to a
      tractional retinal detachment, which can result in functional or complete
      blindness. Recent development of peripheral retinal ablative therapy using laser
      photocoagulation has resulted in the possibility of markedly decreasing the
      incidence of this poor visual outcome, but the sequential nature of ROP creates a
      requirement that at-risk preterm infants be examined at proper times to detect
      the changes of ROP before they become permanently destructive. This statement
      presents the attributes on which an effective program for detecting and treating
      ROP could be based, including the timing of initial examination and subsequent
      reexamination intervals.

PMID- 16452385
TI  - Optimizing bone health and calcium intakes of infants, children, and adolescents.
AB  - Most older children and adolescents in the United States currently do not achieve
      the recommended intake of calcium. Maintaining adequate calcium intake during
      childhood and adolescence is necessary for the development of peak bone mass,
      which may be important in reducing the risk of fractures and osteoporosis later
      in life. Optimal calcium intake is especially relevant during adolescence, when
      most bone mineral accretion occurs. Because of the influence of the family's diet
      on the diet of children and adolescents, adequate calcium intake by all members
      of the family is important. Assessment of calcium intake can be performed in the
      physician's office. A well-rounded diet including low-fat dairy products, fruits,
      and vegetables and appropriate physical activity are important for achieving good
      bone health. Establishing these practices in childhood is important so that they
      will be followed throughout the life span.

PMID- 16452386
TI  - Diabetic retinopathy screening.

PMID- 16452387
TI  - Absence of unfavorable effect of atomoxetine on growth in pediatric patients is
      still not demonstrated.

PMID- 16452388
TI  - "Inferiority complex" for a reason.

PMID- 16452389
TI  - A prevalent functional polymorphism of insulin-like growth factor system is not
      associated with perinatal complications in preterm infants.

PMID- 16452390
TI  - Developmental and behavioral services and child welfare.

PMID- 16452391
TI  - A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated
      gene expression in synoviocytes.
AB  - Spleen tyrosine kinase (Syk) is a key regulator of cell signaling induced by
      cytokines or Fc receptor engagement. However, the role of Syk in rheumatoid
      arthritis (RA) is not known yet. We investigated the pathways activated by Syk in
      tumor necrosis factor-alpha (TNFalpha)-stimulated fibroblast-like synoviocytes
      (FLS) using the novel Syk inhibitor N4-(2,2-dimethyl-3-oxo-4H-pyrid[1,4]oxazin-6
      yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine (R406). Using
      immunohistochemistry, Syk was detected in RA synovial tissue (ST), primarily in
      the synovial intimal lining. Western blot analysis demonstrated significantly
      greater amounts of phospho-Syk expression in RA ST compared with osteoarthritis
      ST. The kinase was expressed and functionally activated by TNFalpha in FLS and
      was blocked by R406. Western blot analysis demonstrated that Syk inhibition by
      R406 markedly suppressed TNFalpha-induced c-Jun N-terminal kinase (JNK)
      phosphorylation in FLS, with a modest decrease in extracellular signal-regulated
      kinase phosphorylation. Surprisingly, p38 activation was not affected by R406.
      The Syk inhibitor also decreased TNFalpha-induced mitogen-activated protein
      kinase kinase (MKK) 4 phosphorylation but not MKK3 and MKK6 phosphorylation,
      which is consistent with its selective sparing of p38. The connection between Syk
      and JNK was confirmed by demonstrating decreased phospho-c-Jun protein expression
      and complete inhibition of JNK function in R406-treated cells. R406 also
      suppressed downstream actions of JNK, as determined by activator protein 1
      binding, as well as matrix metalloproteinase 3 gene expression. These data
      demonstrate that Syk activation plays an essential role in TNFalpha-induced
      cytokine and matrix metalloproteinase production in RA FLS, especially by
      suppressing activation of the JNK pathway.

PMID- 16452392
TI  - Enhanced hepatic uptake and bioactivity of type alpha1(I) collagen gene promoter
      specific triplex-forming oligonucleotides after conjugation with cholesterol.
AB  - A triplex-forming oligonucleotide (TFO) specific for type alpha1(I) collagen
      promoter is a promising candidate for treating liver fibrosis. Earlier, we
      determined the pharmacokinetics and biodistribution of TFO after systemic
      administration into normal and fibrotic rats. In this study, we conjugated
      cholesterol to the 3' end of the TFO via a disulfide bond and determined its
      cellular and nuclear uptake and bioactivity using HSC-T6 cell lines in vitro,
      followed by biodistribution at whole-body, organ (liver), and subcellular levels.
      Conjugation with cholesterol had little effect on the triplex-forming ability of
      the TFO with target duplex DNA, and the cellular uptake of (33)P-TFO-cholesterol
      (Chol) increased by 2- to approximately 4-fold. Real-time reverse transcriptase
      polymerase chain reaction analysis after transfection of HSC-T6 cells with TFO
      Chol or TFO indicated that TFO-Chol had higher inhibition on type alpha1(I)
      collagen primary transcript than naked TFO at low concentration (200 nM) but
      showed similar inhibition at higher concentration (500 and 1000 nM). There was
      increase in the inhibition on primary transcript with transfection time. The
      hepatic uptake of (33)P-TFO-Chol after systemic administration was 72.22% of the
      dose compared with 45.8% of (33)P-TFO. There was significant increase in the
      uptake of (33)P-TFO-Chol by hepatic stellate cells and hepatocytes. More
      importantly, the nuclear uptake of TFO-Chol was higher than TFO in cell culture
      system and in vivo studies. In conclusion, TFO-Chol is a potential antifibrotic
      agent.

PMID- 16452393
TI  - Segmental differences in the roles of rho-kinase and protein kinase C in
      mediating vasoconstriction.
AB  - Rho-kinase and protein kinase C (PKC) have each been reported to mediate
      vasoconstriction via calcium sensitization. However, the relative contributions
      of these two kinases to vascular contraction, and whether their roles vary
      between large and small arteries, are largely unknown. We therefore assessed the
      relative roles of rho-kinase and PKC in mediating vasoconstriction in arteries
      from three segments of the aortic and mesenteric vasculature. We studied
      contractile responses of rat isolated thoracic aorta (diameter approximately 2
      mm), superior mesenteric artery (SMA; approximately 1.5 mm), and second order
      branches of the superior mesenteric artery (BMA; approximately 300 mum). The
      roles of rho-kinase and PKC in mediating contractile responses to phenylephrine,
      9,11-dideoxy-9,11-methanoepoxy prostaglandin F(2alpha) (U46619), and KCl were
      assessed by using the rho-kinase inhibitor R-[+]-trans-N-[4-pyridyl]-4-[1
      aminoethyl]-cycloheaxanecarboxamide (Y-27632) (1 and 10 muM) and the PKC
      inhibitor 3-[1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3-yl)
      maleimide (Ro 31-8220) (5 muM). Contractile responses of aorta and SMA were
      reduced by either 1 or 10 muM Y-27632 (P < 0.05), whereas responses of BMA were
      reduced by 10 muM (P < 0.05) but not 1 muM Y-27632. In contrast, Ro 31-8220
      partly reduced contractile responses in aorta and SMA (P < 0.05), but it
      abolished responses of BMA (P < 0.05). Cotreatment with Y-27632 and Ro 31-8220
      markedly attenuated contractile responses to phenylephrine and KCl in all
      vessels, but it had only a moderate inhibitory effect on responses to U46619 in
      aorta and SMA. Thus, contractile responses of the larger arteries can involve
      both rho-kinase and PKC to varying degrees. Conversely, contractile responses of
      small mesenteric resistance arteries seem to be mediated exclusively by PKC, with
      no apparent role for rho-kinase.

PMID- 16452394
TI  - Follow-up of occult bone lesions detected at MR imaging: systematic review.
AB  - PURPOSE: To perform a systematic review of the literature regarding the natural
      course of posttraumatic occult bone lesions (often referred to as bone bruises)
      detected at magnetic resonance (MR) imaging. MATERIALS AND METHODS: A systematic
      review of the literature was performed by searching the MEDLINE database (from
      January 1966 to February 2003) with the keywords bone bruise, trauma, follow-up,
      and MRI. Keywords were linked by using the Boolean operator AND. Studies were
      included if all of the following criteria were fulfilled: patients sustained
      trauma, MR imaging was used as a diagnostic method, results of clinical or MR
      imaging follow-up were available, and study was written in English, Dutch,
      German, French, Spanish, Italian, Swedish, Danish, or Norwegian. The quality of
      each study was assessed by using a standardized criteria set, and kappa
      statistics were estimated to rate the level of agreement between the two
      reviewers. Results were compared with regard to study design and quality scores.
      RESULTS: The MEDLINE search identified 266 articles, 13 of which met the
      inclusion criteria. The quality of the included studies was moderate. The two
      reviewers initially agreed on 179 quality items (kappa = 0.84). The study
      population was generally small, and follow-up periods ranged from 1 to 73 months.
      Four different classification systems were used, and in two studies bone bruise
      was not specified. Study results suggest a generally good clinical prognosis of
      bone bruises. Normalization of MR imaging appearance is possible and is most
      often encountered after the occurrence of reticular lesions. Cartilage loss at
      follow-up is often found in cases of initial cartilage damage (impaction or
      osteochondral fracture). CONCLUSION: In general, a healing response was often
      encountered after sustained posttraumatic occult bone lesions. The initial MR
      imaging appearance appears to have prognostic value.

PMID- 16452395
TI  - Follow-up of posttraumatic ligamentous and meniscal knee lesions detected at MR
      imaging: systematic review.
AB  - PURPOSE: To perform a systematic review of the literature regarding the natural
      course of ligamentous and meniscal knee lesions detected at magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: The MEDLINE database was searched from
      January 1966 to February 2003. Studies were included if all of the following
      criteria were met: patients had collateral ligament, cruciate ligament, or
      meniscal lesions; MR imaging was performed in all patients; study included a
      group and/or subgroup of patients who underwent conservative treatment during
      follow-up; patients returned to the clinic for follow-up and clinical data or MR
      imaging outcomes were noted; and article was written in English, Dutch, German,
      French, Spanish, Italian, Swedish, Danish, or Norwegian. The quality of each
      study was assessed by using a standardized criteria set, and kappa statistics
      were used to grade the level of agreement between the two reviewers. Studies with
      quality scores of 8 or more were designated as high quality. Results were
      compared with regard to study design and quality scores. RESULTS: The literature
      search identified 649 articles, and 11 studies (five on posterior cruciate
      ligament [PCL] injuries, five on anterior cruciate ligament [ACL] injuries, and
      one on meniscal injuries) met the inclusion criteria. No studies on the follow-up
      of collateral ligament injuries were identified. Four studies were of high
      quality, and the kappa value for quality items was 0.80. Between 77% and 93% of
      the partial or complete PCL ruptures regained continuity. In cases of partial or
      total ACL rupture, repair of continuity was also possible. A possible association
      between MR imaging continuity and clinical stability was identified. CONCLUSION:
      The ACL and PCL can regain continuity after partial or complete rupture. On the
      basis of this review, no conclusions can be drawn about the natural course of
      meniscal or collateral ligament injury seen at MR imaging.

PMID- 16452396
TI  - Suspected aortic dissection and other aortic disorders: multi-detector row CT in
      373 cases in the emergency setting.
AB  - PURPOSE: To retrospectively review the authors' experience with multi-detector
      row computed tomography (CT) for detection of aortic dissection in the emergency
      setting. MATERIALS AND METHODS: The investigation was institutional review board
      approved, did not require informed patient consent, and was HIPAA compliant. In
      373 clinical evaluations in the emergency setting, 365 patients suspected of
      having aortic dissection and/or other aortic disorders underwent multidetector
      CT. Criteria for acute aortic disorder were confirmed by using surgical and
      pathologic diagnoses or findings at clinical follow-up and any subsequent imaging
      as the reference standard. Positive cases were characterized according to type of
      disorder interpreted. Resulting sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV), and accuracy were calculated by
      using two-way contingency tables. All cases found to be negative for acute aortic
      disorders were grouped according to alternative CT findings. RESULTS: Sixty-seven
      (18.0%) of the 373 cases were interpreted as positive for acute aortic disorder.
      One hundred twelve acute aortic disorders were identified in these 67 cases: 23
      acute aortic dissections, 14 acute aortic intramural hematomas, 20 acute
      penetrating aortic ulcers, 44 new or enlarging aortic aneurysms, and 11 acute
      aortic ruptures. Three hundred five (81.8%) cases were interpreted as negative
      for acute aortic disorder. In 48 negative cases, multidetector CT depicted
      alternative findings that accounted for the clinical presentation. Of these,
      three included both acute aortic disorders and alternative findings, and 45
      included only alternative findings. One (0.3%) case was indeterminate for acute
      aortic disorder. Overall, 112 findings were interpreted as positive for acute
      aortic disorder, an alternative finding, or both at CT. No interpretations were
      false-positive, one was false-negative, 67 were true-positive, and 304 were true
      negative. Sensitivity, specificity, PPV, NPV, and accuracy were 99% (67 of 68),
      100% (304 of 304), 100% (67 of 67), 99.7% (304 of 305), and 99.5% (371 of 373),
      respectively. CONCLUSION: The positivity rate for acute aortic dissection or
      other acute aortic disorder in 373 cases examined at multi-detector row CT was
      18.0%.

PMID- 16452397
TI  - Pituitary macroadenomas: preoperative evaluation of consistency with diffusion
      weighted MR imaging--initial experience.
AB  - PURPOSE: To prospectively evaluate use of diffusion-weighted (DW) magnetic
      resonance (MR) images and apparent diffusion coefficient (ADC) maps for
      determination of the consistency of macroadenomas. MATERIALS AND METHODS: The
      study protocol was approved by the institutional ethics committee, and informed
      consent was obtained from all patients. Twenty-two patients with pituitary
      macroadenoma (10 men, 12 women; mean age, 54 years +/- 17.09 [standard
      deviation]; range, 21-75 years) were examined. All patients underwent MR
      examination, which included T1-weighted spin-echo and T2-weighted turbo spin-echo
      DW imaging with ADC mapping and contrast material-enhanced T1-weighted spin-echo
      imaging. Regions of interest (ROIs) were drawn in the macroadenomas and in normal
      white matter on DW images, ADC maps, and conventional MR images. Consistency of
      macroadenomas was evaluated at surgery and was classified as soft, intermediate,
      or hard. Histologic examination was performed on surgical specimens of
      macroadenomas. Mean ADC values, signal intensity (SI) ratios of tumor to white
      matter within ROIs on conventional and DW MR images, and degree of enhancement
      were compared with tumor consistency and with percentage of collagen content at
      histologic examination by using analysis of variance for linear trend. RESULTS:
      The mean value of ADC in the soft group was (0.663 +/- 0.109) x 10(-3) mm(2)/sec;
      in the intermediate group, (0.842 +/- 0.081) x 10(-3) mm(2)/sec; and in the hard
      group, (1.363 +/- 0.259) x 10(-3) mm(2)/sec. Statistical analysis revealed a
      significant correlation between tumor consistency and ADC values, DW image SI
      ratios, T2-weighted image SI ratios, and percentage of collagen content (P <
      .001, analysis of variance). No other statistically significant correlations were
      found. CONCLUSION: Findings in this study suggest that DW MR images with ADC maps
      can provide information about the consistency of macroadenomas.

PMID- 16452398
TI  - Structural model reveals key interactions in the assembly of the pregnane X
      receptor/corepressor complex.
AB  - The human pregnane X receptor (PXR), also known as steroid and xenobiotic
      receptor, is a member of the orphan nuclear receptors and mediates the mammalian
      xenobiotic response with broad specificity and implications for drug clearance.
      The mouse pregnane X receptor is highly similar to the human ortholog in
      structure but with subtle species differentiation in the ligand binding domain
      (LBD). The C-terminal helix named alphaAF or AF-2 helix in other nuclear
      receptors is responsible for transcription activation by recruiting coactivators
      through conformational change. In the absence of ligands, PXR can also repress
      gene expression by interacting with transcriptional corepressors, such as the
      silencing mediator for retinoid and thyroid hormone receptor (SMRT). We first
      constructed homology models of the complete LBD with two SMRT nuclear receptor
      (NR)-interacting domains (ID1 and ID2), respectively. We then performed energy
      minimization and molecular dynamics simulations on these systems to study the
      specific interactions between the interacting domains and LBD. Further
      experimental results supported and validated the observed preference of SMRT
      toward ID2 over ID1. Our modeling results revealed the key interactions that
      account for the binding preference. Here, we propose structural models of the PXR
      LBD/SMRT-ID1 and PXR-LBD/SMRT-ID2 complexes to understand their molecular
      interactions and potential inhibitory mechanism.

PMID- 16452399
TI  - An uncharged region within the N terminus of the P2X6 receptor inhibits its
      assembly and exit from the endoplasmic reticulum.
AB  - ATP-gated P2X receptors are trimeric complexes formed by the homomeric or
      heteromeric assembly of seven different subunits. We have shown previously that,
      unlike all of the other P2X subunits, the P2X6 subunit cannot form homomeric
      receptors and when expressed alone is retained in the endoplasmic reticulum (ER)
      in monomeric form (J Biol Chem 280: 107591-10765, 2005). However, other studies
      have shown that P2X6 can form functional heteromeric receptors with P2X2 and P2X4
      subunits. In this study, we used a combination of immunocytochemistry, surface
      biotinylation, and atomic force microscopy to investigate the assembly and
      trafficking of the P2X6 subunit, both alone and as part of a heteromer. We show
      that as a heteromer, it exits the ER and is either stably expressed at the cell
      surface or constitutively internalized, depending on its partner. Through the use
      of targeted mutation, we demonstrate that an uncharged region at the N terminus
      of P2X6 exerts an inhibitory effect on its assembly and export from the ER. When
      this region is removed, or when charge is added to it, P2X6 forms homotrimeric
      assemblies, undergoes complex glycosylation and is delivered to the plasma
      membrane, albeit less efficiently than the P2X2 receptor. The N-terminal mutants
      were, however, nonfunctional. Substituting the uncharged 14-amino acid N-terminal
      region for the equivalent region of P2X2 increased ER retention but was not
      sufficient to prevent the formation of functional homomeric receptors. We propose
      that the N terminus of the P2X6 subunit contributes to a mechanism that prevents
      the inappropriate export and plasma membrane expression of nonfunctional P2X
      receptors.

PMID- 16452400
TI  - Peroxisome proliferator-activated receptor gamma-independent repression of
      prostate-specific antigen expression by thiazolidinediones in prostate cancer
      cells.
AB  - In light of the potential use of the thiazolidinedione family of peroxisome
      proliferator-activated receptor-gamma (PPARgamma) agonists in prostate cancer
      treatment, this study assessed the mechanism by which these agents suppress
      prostate-specific antigen (PSA) secretion in prostate cancer cells. Two lines of
      evidence indicate that the effect of thiazolidinediones on PSA down-regulation is
      independent of PPARgamma activation. First, this thiazolidinedione-mediated PSA
      down-regulation is structure-specific irrespective of the relative PPARgamma
      agonist potency. Second, the PPARgamma-inactive analogs of troglitazone and
      ciglitazone [Delta2TG (5-[4-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl-methoxy)
      benzylidene]-thiazolidine-2,4-dione) and Delta2CG (5-[4-(1-methyl
      cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione), respectively] exhibit
      higher potency than the parent compound in inhibiting dihydrotestosterone (DHT)
      stimulated PSA secretion. Although 10 microM troglitazone and Delta2TG
      significantly inhibit PSA secretion, they do not alter the expression level of
      androgen receptor (AR) or interfere with DHT-activated nuclear translocation of
      AR. However, reporter gene and chromatin immunoprecipitation studies indicate
      that troglitazone and Delta2TG block AR recruitment to the androgen response
      elements within the PSA promoter. Thus, this study raises the question of whether
      the ability of oral troglitazone to reduce PSA levels in prostate cancer patients
      is therapeutically relevant. A major concern is that the concentration for
      troglitazone to mediate antitumor effects is severalfold higher than that of PSA
      down-regulation, which is difficult to attain at therapeutic doses. Nevertheless,
      it is noteworthy that troglitazone and Delta2TG at high doses were able to
      inhibit AR expression. From a translational perspective, separation of PPARgamma
      agonist activity from AR down-regulation provides a molecular basis to use
      troglitazone as a platform to design AR-ablative agents.

PMID- 16452401
TI  - Keeping their options open: acute versus persistent infections.

PMID- 16452402
TI  - The global regulatory proteins LetA and RpoS control phospholipase A,
      lysophospholipase A, acyltransferase, and other hydrolytic activities of
      Legionella pneumophila JR32.
AB  - Legionella pneumophila possesses a variety of secreted and cell-associated
      hydrolytic activities that could be involved in pathogenesis. The activities
      include phospholipase A, lysophospholipase A, glycerophospholipid:cholesterol
      acyltransferase, lipase, protease, phosphatase, RNase, and p
      nitrophenylphosphorylcholine (p-NPPC) hydrolase. Up to now, there have been no
      data available on the regulation of the enzymes in L. pneumophila and no data at
      all concerning the regulation of bacterial phospholipases A. Therefore, we used
      L. pneumophila mutants in the genes coding for the global regulatory proteins
      RpoS and LetA to investigate the dependency of hydrolytic activities on a global
      regulatory network proposed to control important virulence traits in L.
      pneumophila. Our results show that both L. pneumophila rpoS and letA mutants
      exhibit on the one hand a dramatic reduction of secreted phospholipase A and
      glycerophospholipid:cholesterol acyltransferase activities, while on the other
      hand secreted lysophospholipase A and lipase activities were significantly
      increased during late logarithmic growth phase. The cell-associated phospholipase
      A, lysophospholipase A, and p-NPPC hydrolase activities, as well as the secreted
      protease, phosphatase, and p-NPPC hydrolase activities were significantly
      decreased in both of the mutant strains. Only cell-associated phosphatase
      activity was slightly increased. In contrast, RNase activity was not affected.
      The expression of plaC, coding for a secreted acyltransferase, phospholipase A,
      and lysophospholipase A, was found to be regulated by LetA and RpoS. In
      conclusion, our results show that RpoS and LetA affect phospholipase A,
      lysophospholipase A, acyltransferase, and other hydrolytic activities of L.
      pneumophila in a similar way, thereby corroborating the existence of the
      LetA/RpoS regulation cascade.

PMID- 16452404
TI  - Biosynthesis of a natural polyketide-isoprenoid hybrid compound, furaquinocin A:
      identification and heterologous expression of the gene cluster.
AB  - Furaquinocin (FQ) A, produced by Streptomyces sp. strain KO-3988, is a natural
      polyketide-isoprenoid hybrid compound that exhibits a potent antitumor activity.
      As a first step toward understanding the biosynthetic machinery of this unique
      and pharmaceutically useful compound, we have cloned an FQ A biosynthetic gene
      cluster by taking advantage of the fact that an isoprenoid biosynthetic gene
      cluster generally exists in flanking regions of the mevalonate (MV) pathway gene
      cluster in actinomycetes. Interestingly, Streptomyces sp. strain KO-3988 was the
      first example of a microorganism equipped with two distinct mevalonate pathway
      gene clusters. We were able to localize a 25-kb DNA region that harbored FQ A
      biosynthetic genes (fur genes) in both the upstream and downstream regions of one
      of the MV pathway gene clusters (MV2) by using heterologous expression in
      Streptomyces lividans TK23. This was the first example of a gene cluster
      responsible for the biosynthesis of a polyketide-isoprenoid hybrid compound. We
      have also confirmed that four genes responsible for viguiepinol [3-hydroxypimara
      9(11),15-diene] biosynthesis exist in the upstream region of the other MV pathway
      gene cluster (MV1), which had previously been cloned from strain KO-3988. This
      was the first example of prokaryotic enzymes with these biosynthetic functions.
      By phylogenetic analysis, these two MV pathway clusters were identified as
      probably being independently distributed in strain KO-3988 (orthologs), rather
      than one cluster being generated by the duplication of the other cluster
      (paralogs).

PMID- 16452403
TI  - Oxygen reactivity of PutA from Helicobacter species and proline-linked oxidative
      stress.
AB  - Proline is converted to glutamate in two successive steps by the proline
      utilization A (PutA) flavoenzyme in gram-negative bacteria. PutA contains a
      proline dehydrogenase domain that catalyzes the flavin adenine dinucleotide (FAD)
      dependent oxidation of proline to delta1-pyrroline-5-carboxylate (P5C) and a P5C
      dehydrogenase domain that catalyzes the NAD+-dependent oxidation of P5C to
      glutamate. Here, we characterize PutA from Helicobacter hepaticus (PutA(Hh)) and
      Helicobacter pylori (PutA(Hp)) to provide new insights into proline metabolism in
      these gastrointestinal pathogens. Both PutA(Hh) and PutA(Hp) lack DNA binding
      activity, in contrast to PutA from Escherichia coli (PutA(Ec)), which both
      regulates and catalyzes proline utilization. PutA(Hh) and PutA(Hp) display
      catalytic activities similar to that of PutA(Ec) but have higher oxygen
      reactivity. PutA(Hh) and PutA(Hp) exhibit 100-fold-higher turnover numbers
      (approximately 30 min(-1)) than PutA(Ec) (<0. 3 min(-1)) using oxygen as an
      electron acceptor during catalytic turnover with proline. Consistent with
      increased oxygen reactivity, PutA(Hh) forms a reversible FAD-sulfite adduct. The
      significance of increased oxygen reactivity in PutA(Hh) and PutA(Hp) was probed
      by oxidative stress studies in E. coli. Expression of PutA(Ec) and PutA from
      Bradyrhizobium japonicum, which exhibit low oxygen reactivity, does not diminish
      stress survival rates of E. coli cell cultures. In contrast, PutA(Hp) and
      PutA(Hh) expression dramatically reduces E. coli cell survival and is correlated
      with relatively lower proline levels and increased hydrogen peroxide formation.
      The discovery of reduced oxygen species formation by PutA suggests that proline
      catabolism may influence redox homeostasis in the ecological niches of these
      Helicobacter species.

PMID- 16452405
TI  - Nickel represses the synthesis of the nickel permease NixA of Helicobacter
      pylori.
AB  - Nickel acquisition is necessary for urease activity, a major virulence factor of
      the human gastric pathogen Helicobacter pylori. NixA was identified as a specific
      nickel uptake system in this organism. Addition of small amounts of nickel to
      media strongly stimulates urea hydrolysis. On the other hand, high nickel
      concentrations are deleterious to cell growth. As a possible protective reaction,
      nickel uptake seems to be reduced in H. pylori grown in nickel-rich media. These
      observations led to investigations of regulation of the expression of the nickel
      permease NixA. We found that increasing the nickel concentration in media reduced
      the amount of NixA. In order to address the question of whether this phenomenon
      was subject to transcriptional or translational regulation, we quantified nixA
      mRNA from H. pylori by real-time PCR. The amount of nixA mRNA was gradually
      reduced five- to sevenfold in a time- and concentration-dependent manner.
      Repression could be measured as soon as 5 min after nickel addition, and the
      maximum repression occurred after 20 to 30 min. The maximum repression was
      obtained with an external nickel concentration of 100 microM. The observed nickel
      repression of NixA was dependent on nikR encoding the nickel-responsive
      regulatory protein NikR. In conclusion, we demonstrated that synthesis of the
      NixA nickel permease of H. pylori shows nickel-responsive regulation mediated by
      NikR to maintain the balance between effective nickel acquisition and a toxic
      overload.

PMID- 16452406
TI  - Archaeal and bacterial SecD and SecF homologs exhibit striking structural and
      functional conservation.
AB  - The majority of secretory proteins are translocated into and across hydrophobic
      membranes via the universally conserved Sec pore. Accessory proteins, including
      the SecDF-YajC Escherichia coli membrane complex, are required for efficient
      protein secretion. E. coli SecDF-YajC has been proposed to be involved in the
      membrane cycling of SecA, the cytoplasmic bacterial translocation ATPase, and in
      the stabilizing of SecG, a subunit of the Sec pore. While there are no identified
      archaeal homologs of either SecA or SecG, many archaea possess homologs of SecD
      and SecF. Here, we present the first study that addresses the function of
      archaeal SecD and SecF homologs. We show that the SecD and SecF components in the
      model archaeon Haloferax volcanii form a cytoplasmic membrane complex in the
      native host. Furthermore, as in E. coli, an H. volcanii deltasecFD mutant strain
      exhibits both severe cold sensitivity and a Sec-specific protein translocation
      defect. Taken together, these results demonstrate significant functional
      conservation among the prokaryotic SecD and SecF homologs despite the distinct
      composition of their translocation machineries.

PMID- 16452407
TI  - Lactose-over-glucose preference in Bifidobacterium longum NCC2705: glcP, encoding
      a glucose transporter, is subject to lactose repression.
AB  - Analysis of culture supernatants obtained from Bifidobacterium longum NCC2705
      grown on glucose and lactose revealed that glucose utilization is impaired until
      depletion of lactose. Thus, unlike many other bacteria, B. longum preferentially
      uses lactose rather than glucose as the primary carbon source. Glucose uptake
      experiments with B. longum cells showed that glucose transport was repressed in
      the presence of lactose. A comparative analysis of global gene expression
      profiling using DNA arrays led to the identification of only one gene repressed
      by lactose, the putative glucose transporter gene glcP. The functionality of GlcP
      as glucose transporter was demonstrated by heterologous complementation of a
      glucose transport-deficient Escherichia coli strain. Additionally, GlcP exhibited
      the highest substrate specificity for glucose. Primer extension and real-time PCR
      analyses confirmed that expression of glcP was mediated by lactose. Hence, our
      data demonstrate that the presence of lactose in culture medium leads to the
      repression of glucose transport and transcriptional down-regulation of the
      glucose transporter gene glcP. This may reflect the highly adapted life-style of
      B. longum in the gastrointestinal tract of mammals.

PMID- 16452408
TI  - CcpA causes repression of the phoPR promoter through a novel transcription start
      site, P(A6).
AB  - The Bacillus subtilis PhoPR two-component system is directly responsible for
      activation or repression of Pho regulon genes in response to phosphate
      deprivation. The response regulator, PhoP, and the histidine kinase, PhoR, are
      encoded in a single operon with a complex promoter region that contains five
      known transcription start sites, which respond to at least two regulatory
      proteins. We report here the identification of another direct regulator of phoPR
      transcription, carbon catabolite protein A, CcpA. This regulator functions in the
      presence of glucose or other readily metabolized carbon sources. The maximum
      derepression of phoPR expression in a ccpA mutant compared to a wild-type stain
      was observed under excess phosphate conditions with glucose either throughout
      growth in a high-phosphate defined medium or in a low-phosphate defined medium
      during exponential growth, a growth condition when phoPR transcription is low in
      a wild-type strain due to the absence of autoinduction. Either HPr or Crh were
      sufficient to cause CcpA dependent repression of the phoPR promoter in vivo. A
      ptsH1 (Hpr) crh double mutant completely relieves phoPR repression during
      phosphate starvation but not during phosphate replete growth. In vivo and in
      vitro studies showed that CcpA repressed phoPR transcription by binding directly
      to the cre consensus sequence present in the promoter. Primer extension and in
      vitro transcription studies revealed that the CcpA regulation of phoPR
      transcription was due to repression of P(A6), a previously unidentified promoter
      positioned immediately upstream of the cre box. Esigma(A) was sufficient for
      transcription of P(A6), which was repressed by CcpA in vitro. These studies
      showed direct repression by CcpA of a newly discovered Esigma(A)-responsive phoPR
      promoter that required either Hpr or Crh in vivo for direct binding to the
      putative consensus cre sequence located between P(A6) and the five downstream
      promoters characterized previously.

PMID- 16452409
TI  - The bacteriophage T4 inhibitor and coactivator AsiA inhibits Escherichia coli RNA
      Polymerase more rapidly in the absence of sigma70 region 1.1: evidence that
      region 1.1 stabilizes the interaction between sigma70 and core.
AB  - The N-terminal region (region 1.1) of sigma70, the primary sigma subunit of
      Escherichia coli RNA polymerase, is a negatively charged domain that affects the
      DNA binding properties of sigma70 regions 2 and 4. Region 1.1 prevents the
      interaction of free sigma70 with DNA and modulates the formation of stable (open)
      polymerase/promoter complexes at certain promoters. The bacteriophage T4 AsiA
      protein is an inhibitor of sigma70-dependent transcription from promoters that
      require an interaction between sigma70 region 4 and the -35 DNA element and is
      the coactivator of transcription at T4 MotA-dependent promoters. Like AsiA, the
      T4 activator MotA also interacts with sigma70 region 4. We have investigated the
      effect of region 1.1 on AsiA inhibition and MotA/AsiA activation. We show that
      sigma70 region 1.1 is not required for MotA/AsiA activation at the T4 middle
      promoter P(uvsX). However, the rate of AsiA inhibition and of MotA/AsiA
      activation of polymerase is significantly increased when region 1.1 is missing.
      We also find that RNA polymerase reconstituted with sigma70 that lacks region 1.1
      is less stable than polymerase with full-length sigma70. Our previous work has
      demonstrated that the AsiA-inhibited polymerase is formed when AsiA binds to
      region 4 of free sigma70 and then the AsiA/sigma70 complex binds to core. Our
      results suggest that in the absence of region 1.1, there is a shift in the
      dynamic equilibrium between polymerase holoenzyme and free sigma70 plus core,
      yielding more free sigma70 at any given time. Thus, the rate of AsiA inhibition
      and AsiA/MotA activation increases when RNA polymerase lacks region 1.1 because
      of the increased availability of free sigma70. Previous work has argued both for
      and against a direct interaction between regions 1.1 and 4. Using an E. coli two
      hybrid assay, we do not detect an interaction between these regions. This result
      supports the idea that the ability of region 1.1 to prevent DNA binding by free
      sigma70 arises through an indirect effect.

PMID- 16452410
TI  - Sll1717 affects the redox state of the plastoquinone pool by modulating quinol
      oxidase activity in thylakoids.
AB  - A Synechocystis sp. strain PCC 6803 mutant lacking CtaI, a main subunit of
      cytochrome c oxidase, is not capable of growing at light intensities below 5
      micromol photons m(-2) s(-1), presumably due to an overreduced plastoquinone pool
      in the thylakoid membrane. Upon selection for growth at light intensities below 5
      micromol photons m(-2) s(-1), a secondary mutant was generated that retained the
      CtaI deletion and had fully assembled photosystem II complexes; in this secondary
      mutant (pseudorevertant), oxygen evolution and respiratory activities were
      similar to those in the wild type. Functional complementation of the original
      CtaI-less strain to low-light tolerance by transformation with restriction
      fragments of genomic DNA of the pseudorevertant and subsequent mapping of the
      pseudoreversion site showed that the point mutation led to a Ser186Cys
      substitution in Sll1717, a protein of as-yet-unknown function and with a
      predicted ATP/GTP-binding domain. This mutation caused a decrease in the
      plastoquinone pool reduction level of thylakoids compared to that observed for
      the wild type. Based on a variety of experimental evidence, the most plausible
      mechanism to cause this effect is an activation of plastoquinol oxidation in
      thylakoids by the quinol oxidase CydAB that occurs without upregulation of the
      corresponding gene and that may be caused by an increased CydAB activity in
      thylakoids, conceivably due to altered CydAB sorting between cytoplasmic and
      thylakoid membranes. Sll1717 appears to be unique to Synechocystis sp. strain PCC
      6803 and has a close homologue encoded in the genome of this organism. The
      transcript level of sll1717 is low, which suggests that the corresponding protein
      is regulatory rather than structural.

PMID- 16452411
TI  - The Brucella abortus xthA-1 gene product participates in base excision repair and
      resistance to oxidative killing but is not required for wild-type virulence in
      the mouse model.
AB  - Exonuclease III, encoded by the xthA gene, plays a central role in the base
      excision pathway of DNA repair in bacteria. Studies with Escherichia coli xthA
      mutants have also shown that exonuclease III participates in the repair of
      oxidative damage to DNA. An isogenic xthA-1 mutant (designated CAM220) derived
      from virulent Brucella abortus 2308 exhibited increased sensitivity to the
      alkylating agent methyl methanesulfonate (MMS) compared to the parent strain. In
      contrast, 2308 and the isogenic xthA-1 mutant displayed similar levels of
      resistance to the DNA cross-linker mitomycin C. These phenotypic properties are
      those that would be predicted for a strain defective in base excision repair. The
      B. abortus xthA-1 mutant also displayed reduced resistance to killing by H2O2 and
      the ONOO(-)-generating compound 3-morpholinosydnonimine (SIN-1) compared to
      strain 2308, indicating that the xthA-1 gene product participates in protecting
      B. abortus 2308 from oxidative damage. Introducing a plasmid-borne copy of the
      parental xthA-1 gene into CAM220 restored wild-type resistance of this mutant to
      MMS, H2O2, and SIN-1. Although the B. abortus xthA-1 mutant exhibited increased
      sensitivity to oxidative killing compared to the parental strain in laboratory
      assays, CAM220 and 2308 displayed equivalent spleen colonization profiles in
      C57BL/6 [corrected] mice through 8 weeks postinfection and equivalent
      intracellular survival and replication profiles in cultured murine macrophages.
      Thus, although the xthA-1 gene product participates in base excision repair and
      resistance to oxidative killing in B. abortus 2308, XthA-1 is not required for
      wild-type virulence of this strain in the mouse model.

PMID- 16452412
TI  - The dltABCD operon of Bacillus anthracis sterne is required for virulence and
      resistance to peptide, enzymatic, and cellular mediators of innate immunity.
AB  - In the environment, the gram-positive bacterium Bacillus anthracis persists as a
      metabolically dormant endospore. Upon inoculation into the host the endospores
      germinate and outgrow into vegetative bacilli able to cause disease. The dramatic
      morphogenic changes to the bacterium during germination and outgrowth are
      numerous and include major rearrangement of and modifications to the bacterial
      surface. Such modifications occur during a time in the B. anthracis infectious
      cycle when the bacterium must guard against a multitude of innate immune
      mediators. The dltABCD locus of B. anthracis encodes a cell wall d-alanine
      esterification system that is initiated by transcriptional activation during
      endospore outgrowth. The level of transcription from the dltABCD operon
      determined B. anthracis resistance to cationic antibacterial peptides during
      vegetative growth and cationic peptide, enzymatic, and cellular mediators of
      innate immunity during outgrowth. Mutation of dltABCD was also attenuating in a
      mouse model of infection. We propose that the dltABCD locus is important for
      protection of endosporeforming bacteria from environmental assault during
      outgrowth and that such protection may be critical during the establishment phase
      of anthrax.

PMID- 16452413
TI  - The innate immune modulators staphylococcal complement inhibitor and chemotaxis
      inhibitory protein of Staphylococcus aureus are located on beta-hemolysin
      converting bacteriophages.
AB  - Two newly discovered immune modulators, chemotaxis inhibitory protein of
      Staphylococcus aureus (CHIPS) and staphylococcal complement inhibitor (SCIN),
      cluster on the conserved 3' end of beta-hemolysin (hlb)-converting bacteriophages
      (betaC-phis). Since these betaC-phis also carry the genes for the immune evasion
      molecules staphylokinase (sak) and enterotoxin A (sea), this 8-kb region at the
      3' end of betaC-phi represents an innate immune evasion cluster (IEC). By PCR and
      Southern analyses of 85 clinical Staphylococcus aureus strains and 5 classical
      laboratory strains, we show that 90% of S. aureus strains carry a betaC-phi with
      an IEC. Seven IEC variants were discovered, carrying different combinations of
      chp, sak, or sea (or sep), always in the same 5'-to-3' orientation and on the 3'
      end of a betaC-phi. From most IEC variants we could isolate active bacteriophages
      by mitomycin C treatment, of which lysogens were generated in S. aureus R5 (broad
      phage host). All IEC-carrying bacteriophages integrated into hlb, as was measured
      by Southern blotting of R5 lysogens. Large quantities of the different
      bacteriophages were obtained by mitomycin C treatment of the lysogens, and
      bacteriophages were collected and used to reinfect all lysogenic R5 strains. In
      total, five lytic families were found. Furthermore, phage DNA was isolated and
      digested with EcoR1, revealing that one IEC variant can be found on different
      betaI-phis. In conclusion, the four human-specific innate immune modulators SCIN,
      CHIPS, SAK, and SEA form an IEC that is easily transferred among S. aureus
      strains by a diverse group of beta-hemolysin-converting bacteriophages.

PMID- 16452414
TI  - The transcriptional antiterminator RfaH represses biofilm formation in
      Escherichia coli.
AB  - We investigated the influence of regulatory and pathogenicity island-associated
      factors (Hha, RpoS, LuxS, EvgA, RfaH, and tRNA5Leu) on biofilm formation by
      uropathogenic Escherichia coli (UPEC) strain 536. Only inactivation of rfaH,
      which encodes a transcriptional antiterminator, resulted in increased initial
      adhesion and biofilm formation by E. coli 536. rfaH inactivation in nonpathogenic
      E. coli K-12 isolate MG1655 resulted in the same phenotype. Transcriptome
      analysis of wild-type strain 536 and an rfaH mutant of this strain revealed that
      deletion of rfaH correlated with increased expression of flu orthologs. flu
      encodes antigen 43 (Ag43), which mediates autoaggregation and biofilm formation.
      We confirmed that deletion of rfaH leads to increased levels of flu and flu-like
      transcripts in E. coli K-12 and UPEC. Supporting the hypothesis that RfaH
      represses biofilm formation through reduction of the Ag43 level, the increased
      biofilm phenotype of E. coli MG1655rfaH was reversed upon inactivation of flu.
      Deletion of the two flu orthologs, however, did not modify the behavior of mutant
      536rfaH. Our results demonstrate that the strong initial adhesion and biofilm
      formation capacities of strain MG1655rfaH are mediated by both increased steady
      state production of Ag43 and likely increased Ag43 presentation due to null rfaH
      dependent lipopolysaccharide depletion. Although the roles of rfaH in the biofilm
      phenotype are different in UPEC strain 536 and K-12 strain MG1655, this study
      shows that RfaH, in addition to affecting the expression of bacterial virulence
      factors, also negatively controls expression and surface presentation of Ag43 and
      possibly another Ag43-independent factor(s) that mediates cell-cell interactions
      and biofilm formation.

PMID- 16452415
TI  - Characterization of the twin-arginine translocase secretion system of
      Mycobacterium smegmatis.
AB  - The twin-arginine translocation (TAT) system secretes fully folded proteins that
      contain a twin-arginine motif within their signal sequence across the cytoplasmic
      membrane in bacteria. Using a green fluorescent protein fused with a TAT signal
      sequence, we demonstrated that Mycobacterium smegmatis contains a TAT system. By
      inactivating individual genes, we showed that three genes (tatA, tatB, and tatC)
      are required for a functional TAT system in M. smegmatis. The tat mutants
      exhibited a decreased growth rate and altered colony morphology compared to the
      parent strain. Comparison of the secreted proteins of the deltatatC and parent
      strain by two-dimensional polyacrylamide gel electrophoresis revealed an
      alteration in the secretion of at least five proteins, and one of the major TAT
      dependent secreted proteins was identified as beta-lactamase (BlaS). The genome
      of M. smegmatis was analyzed with the TATFIND program, and 49 putative TAT
      substrates were identified, including the succinate transporter DctP. Because
      disruption of the TAT secretion system has a direct effect on the physiology of
      M. smegmatis and homologs of the TAT proteins are also present in the genome of
      Mycobacterium tuberculosis, the TAT secretion system or its substrates may be
      good candidates for drug or vaccine development.

PMID- 16452416
TI  - Pyruvate:quinone oxidoreductase in Corynebacterium glutamicum: molecular analysis
      of the pqo gene, significance of the enzyme, and phylogenetic aspects.
AB  - Corynebacterium glutamicum recently has been shown to possess pyruvate:quinone
      oxidoreductase (PQO), catalyzing the oxidative decarboxylation of pyruvate to
      acetate and CO2 with a quinone as the electron acceptor. Here, we analyze the
      expression of the C. glutamicum pqo gene, investigate the relevance of the PQO
      enzyme for growth and amino acid production, and perform phylogenetic studies.
      Expression analyses revealed that transcription of pqo is initiated 45 bp
      upstream of the translational start site and that it is organized in an operon
      together with genes encoding a putative metal-activated pyridoxal enzyme and a
      putative activator protein. Inactivation of the chromosomal pqo gene led to the
      absence of PQO activity; however, growth and amino acid production were not
      affected under either condition tested. Introduction of plasmid-bound pqo into a
      pyruvate dehydrogenase complex-negative C. glutamicum strain partially relieved
      the growth phenotype of this mutant, indicating that high PQO activity can
      compensate for the function of the pyruvate dehydrogenase complex. To investigate
      the distribution of PQO enzymes in prokaryotes and to clarify the relationship
      between PQO, pyruvate oxidase (POX), and acetohydroxy acid synthase enzymes, we
      compiled and analyzed the phylogeny of respective proteins deposited in public
      databases. The analyses revealed a wide distribution of PQOs among prokaryotes,
      corroborated the hypothesis of a common ancestry of the three enzymes, and led us
      to propose that the POX enzymes of Lactobacillales were derived from a PQO.

PMID- 16452418
TI  - Characterization of a glutathione metabolic mutant of Mycobacterium tuberculosis
      and its resistance to glutathione and nitrosoglutathione.
AB  - Glutathione is a tripeptide and antioxidant, synthesized at high levels by cells
      during the production of reactive oxygen and nitrogen intermediates. Glutathione
      also serves as a carrier molecule for nitric oxide in the form of S
      nitrosoglutathione. Previous studies from this laboratory have shown that
      glutathione and S-nitrosoglutathione are directly toxic to mycobacteria.
      Glutathione is not transported into the cells as a tripeptide. Extracellular
      glutathione is converted to a dipeptide due to the action of transpeptidase, and
      the dipeptide is then transported into the bacterial cells. The processing of
      glutathione and S-nitrosoglutathione is brought about by the action of the enzyme
      gamma-glutamyl transpeptidase. The function of gamma-glutamyl transpeptidase is
      to cleave glutathione and S-nitrosoglutathione to the dipeptide (Cys-Gly), which
      is then transported into the bacterium by the multicomponent ABC transporter
      dipeptide permease. We have created a mutant strain of Mycobacterium tuberculosis
      lacking this metabolic enzyme. We investigated the sensitivity of this strain to
      glutathione and S-nitrosoglutathione compared to that of the wild-type bacteria.
      In addition, we examined the role of glutathione and/or S-nitrosoglutathione in
      controlling the growth of intracellular M. tuberculosis inside mouse macrophages.

PMID- 16452417
TI  - lbtA and lbtB are required for production of the Legionella pneumophila
      siderophore legiobactin.
AB  - Under iron stress, Legionella pneumophila secretes legiobactin, a nonclassical
      siderophore that is reactive in the chrome azurol S (CAS) assay. Here, we have
      optimized conditions for legiobactin expression, shown its biological activity,
      and identified two genes, lbtA and lbtB, which are involved in legiobactin
      production. lbtA appears to be iron repressed and encodes a protein that has
      significant homology with siderophore synthetases, and FrgA, a previously
      described iron-regulated protein of L. pneumophila. lbtB encodes a protein
      homologous with members of the major facilitator superfamily of multidrug efflux
      pumps. Mutants lacking lbtA or lbtB were defective for legiobactin, producing 40
      to 70% less CAS reactivity in deferrated chemically defined medium (CDM). In
      bioassays, mutant CDM culture supernatants, unlike those of the wild type, did
      not support growth of iron-limited wild-type bacteria in 2',2'-dipyridyl
      containing buffered charcoal yeast extract (BCYE) agar and a ferrous iron
      transport mutant on BCYE agar without added iron. The lbtA mutant was modestly
      defective for growth in deferrated CDM containing the iron chelator citrate,
      indicating that legiobactin is required in conditions of severe iron limitation.
      Complementation of the lbt mutants restored both siderophore expression, as
      measured by the CAS assay and bioassays, and bacterial growth in deferrated,
      citrate-containing media. The lbtA mutant replicated as the wild type did in
      macrophages, amoebae, and the lungs of mice. However, L. pneumophila expresses
      lbtA in the macrophage, suggesting that legiobactin, though not required, may
      play a dispensable role in intracellular growth. The discovery of lbtAB
      represents the first identification of genes required for L. pneumophila
      siderophore expression.

PMID- 16452419
TI  - Disruption of the operon encoding Ehb hydrogenase limits anabolic CO2
      assimilation in the archaeon Methanococcus maripaludis.
AB  - Methanococcus maripaludis is a mesophilic archaeon that reduces CO2 to methane
      with H2 or formate as an energy source. It contains two membrane-bound energy
      conserving hydrogenases, Eha and Ehb. To determine the role of Ehb, a deletion in
      the ehb operon was constructed to yield the mutant, strain S40. Growth of S40 was
      severely impaired in minimal medium. Both acetate and yeast extract were
      necessary to restore growth to nearly wild-type levels, suggesting that Ehb was
      involved in multiple steps in carbon assimilation. However, no differences in the
      total hydrogenase specific activities were found between the wild type and mutant
      in either cell extracts or membrane-purified fractions. Methanogenesis by resting
      cells with pyruvate as the electron donor was also reduced by 30% in S40,
      suggesting a defect in pyruvate oxidation. CO dehydrogenase/acetyl coenzyme A
      (CoA) synthase and pyruvate oxidoreductase had higher specific activities in the
      mutant, and genes encoding these enzymes, as well as AMP-forming acetyl-CoA
      synthetase, were expressed at increased levels. These observations support a role
      for Ehb in anabolic CO2 assimilation in methanococci.

PMID- 16452420
TI  - Characterization of late acyltransferase genes of Yersinia pestis and their role
      in temperature-dependent lipid A variation.
AB  - Yersinia pestis is an important human pathogen that is maintained in flea-rodent
      enzootic cycles in many parts of the world. During its life cycle, Y. pestis
      senses host-specific environmental cues such as temperature and regulates gene
      expression appropriately to adapt to the insect or mammalian host. For example,
      Y. pestis synthesizes different forms of lipid A when grown at temperatures
      corresponding to the in vivo environments of the mammalian host and the flea
      vector. At 37 degrees C, tetra-acylated lipid A is the major form; but at 26
      degrees C or below, hexa-acylated lipid A predominates. In this study, we show
      that the Y. pestis msbB (lpxM) and lpxP homologs encode the acyltransferases that
      add C12 and C(16:1) groups, respectively, to lipid IV(A) to generate the hexa
      acylated form, and that their expression is upregulated at 21 degrees C in vitro
      and in the flea midgut. A Y. pestis deltamsbB deltalpxP double mutant that did
      not produce hexa-acylated lipid A was more sensitive to cecropin A, but not to
      polymyxin B. This mutant was able to infect and block fleas as well as the
      parental wild-type strain, indicating that the low-temperature-dependent change
      to hexa-acylated lipid A synthesis is not required for survival in the flea gut.

PMID- 16452421
TI  - Novel organic hydroperoxide-sensing and responding mechanisms for OhrR, a major
      bacterial sensor and regulator of organic hydroperoxide stress.
AB  - Xanthomonas campestris pv. phaseoli OhrR belongs to a major family of multiple
      cysteine-containing bacterial organic hydroperoxide sensors and transcription
      repressors. Site-directed mutagenesis and subsequent in vivo functional analyses
      revealed that changing any cysteine residue to serine did not alter the ability
      of OhrR to bind to the P1 ohrR-ohr promoter but drastically affected the organic
      hydroperoxide-sensing and response mechanisms of the protein. Xanthomonas OhrR
      requires two cysteine residues, C22 and C127, to sense and respond to organic
      hydroperoxides. Analysis of the free thiol groups in wild-type and mutant OhrRs
      under reducing and oxidizing conditions indicates that C22 is the organic
      hydroperoxide-sensing residue. Exposure to organic hydroperoxides led to the
      formation of an unstable OhrR-C22 sulfenic acid intermediate that could be
      trapped by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole and detected by UV-visible
      spectral analysis in an oxidized C127S-C131S mutant OhrR. In wild-type OhrR, the
      cysteine sulfenic acid intermediate rapidly reacts with the thiol group of C127,
      forming a disulfide bond. The high-performance liquid chromatography-mass
      spectrometry analysis of tryptic fragments of alkylated, oxidized OhrR and
      nonreducing polyacrylamide gel electrophoresis analyses confirmed the formation
      of reversible intersubunit disulfide bonds between C22 and C127. Oxidation of
      OhrR led to cross-linking of two OhrR monomers, resulting in the inactivation of
      its repressor function. Evidence presented here provides insight into a new
      organic hydroperoxide-sensing and response mechanism for OhrRs of the multiple
      cysteine family, the primary bacterial transcription regulator of the organic
      hydroperoxide stress response.

PMID- 16452422
TI  - Inhibition of cell division suppresses heterocyst development in Anabaena sp.
      strain PCC 7120.
AB  - When the filamentous cyanobacterium Anabaena PCC 7120 is exposed to combined
      nitrogen starvation, 5 to 10% of the cells along each filament at semiregular
      intervals differentiate into heterocysts specialized in nitrogen fixation.
      Heterocysts are terminally differentiated cells in which the major cell division
      protein FtsZ is undetectable. In this report, we provide molecular evidence
      indicating that cell division is necessary for heterocyst development. FtsZ,
      which is translationally fused to the green fluorescent protein (GFP) as a
      reporter, is found to form a ring structure at the mid-cell position. SulA from
      Escherichia coli inhibits the GTPase activity of FtsZ in vitro and prevents the
      formation of FtsZ rings when expressed in Anabaena PCC 7120. The expression of
      sulA arrests cell division and suppresses heterocyst differentiation completely.
      The antibiotic aztreonam, which is targeted to the FtsI protein necessary for
      septum formation, has similar effects on both cell division and heterocyst
      differentiation, although in this case, the FtsZ ring is still formed. Therefore,
      heterocyst differentiation is coupled to cell division but independent of the
      formation of the FtsZ ring. Consistently, once the inhibitory pressure of cell
      division is removed, cell division should take place first before heterocyst
      differentiation resumes at a normal frequency. The arrest of cell division does
      not affect the accumulation of 2-oxoglutarate, which triggers heterocyst
      differentiation. Consistently, a nonmetabolizable analogue of 2-oxoglutarate does
      not rescue the failure of heterocyst differentiation when cell division is
      blocked. These results suggest that the control of heterocyst differentiation by
      cell division is independent of the 2-oxoglutarate signal.

PMID- 16452423
TI  - Positive selection of the Hrp pilin HrpE of the plant pathogen Xanthomonas.
AB  - The plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria possesses a
      type III secretion (TTS) system which is encoded by the 23-kb hrp (hypersensitive
      response and pathogenicity) gene cluster. The TTS system is necessary for
      pathogenicity in susceptible hosts and induction of the hypersensitive response
      in resistant plants. At the cell surface, the TTS system is associated with an
      extracellular filamentous structure, the Hrp pilus, which serves as a conduit for
      the transfer of bacterial proteins into the plant cell cytosol. The major pilus
      component, the HrpE pilin, is unique to xanthomonads. Previous work showed that
      HrpE contains two regions: a hypervariable surface-exposed domain, including the
      N-terminal secretion signal, and a C-terminal polymerization domain. In this
      study, the evolutionary rate of the hrpE gene was analyzed. Twenty-one alleles
      were cloned, sequenced, and compared with five known hrpE alleles. The ratio of
      synonymous (K(s)) and nonsynonymous (K(a)) substitution rates shows that parts of
      the HrpE N terminus are subjected to positive selection and the C terminus is
      subjected to purifying selection. The trade-off between positive and purifying
      selection at the very-N terminus allowed us to ascertain the amphipathic alpha
      helical nature of the TTS signal. This is the first report of a surface structure
      from a plant-pathogenic bacterium that evolved under the constraint of positive
      selection and hints to the evolutionary adaptation of this extracellular
      appendage to avoid recognition by the plant defense surveillance system.

PMID- 16452424
TI  - Spo0A-dependent activation of an extended -10 region promoter in Bacillus
      subtilis.
AB  - At the onset of endospore formation in Bacillus subtilis the DNA-binding protein
      Spo0A directly activates transcription from promoters of about 40 genes. One of
      these promoters, Pskf, controls expression of an operon encoding a killing factor
      that acts on sibling cells. AbrB-mediated repression of Pskf provides one level
      of security ensuring that this promoter is not activated prematurely. However,
      Spo0A also appears to activate the promoter directly, since Spo0A is required for
      Pskf activity in a DeltaabrB strain. Here we investigate the mechanism of Pskf
      activation. DNase I footprinting was used to determine the locations at which
      Spo0A bound to the promoter, and mutations in these sites were found to
      significantly reduce promoter activity. The sequence near the -10 region of the
      promoter was found to be similar to those of extended -10 region promoters, which
      contain a TRTGn motif. Mutational analysis showed that this extended -10 region,
      as well as other base pairs in the -10 region, is required for Spo0A-dependent
      activation of the promoter. We found that a substitution of the consensus base
      pair for the nonconsensus base pair at position -9 of Pskf produced a promoter
      that was active constitutively in both deltaabrB and deltaspo0A deltaabrB
      strains. Therefore, the base pair at position -9 of Pskf makes its activity
      dependent on Spo0A binding, and the extended -10 region motif of the promoter
      contributes to its high level of activity.

PMID- 16452426
TI  - Active-site residues in the type IV prepilin peptidase homologue PibD from the
      archaeon Sulfolobus solfataricus.
AB  - Archaeal preflagellin peptidases and bacterial type IV prepilin peptidases belong
      to a family of aspartic acid proteases that cleave the leader peptides of
      precursor proteins with type IV prepilin signal sequences. The substrate
      repertoire of PibD from the crenarchaeon Sulfolobus solfataricus is unusually
      diverse. In addition to flagellin, PibD cleaves three sugar-binding proteins
      unique to this species and a number of proteins with unknown function. Here we
      demonstrate that PibD contains two aspartic acid residues that are essential for
      cleavage activity. An additional pair of aspartic acids in a large cytoplasmic
      loop is also important for function and is possibly involved in leader peptide
      recognition. Combining the results of transmembrane segment predictions and
      cysteine-labeling experiments, we suggest a membrane topology model for PibD with
      the active-site aspartic acid residues exposed to the cytosol.

PMID- 16452425
TI  - The genome of the novel phage Rtp, with a rosette-like tail tip, is homologous to
      the genome of phage T1.
AB  - A new Escherichia coli phage, named Rtp, was isolated and shown to be closely
      related to phage T1. Electron microscopy revealed that phage Rtp has a
      morphologically unique tail tip consisting of four leaf-like structures arranged
      in a rosette, whereas phage T1 has thinner, flexible leaves that thicken toward
      the ends. In contrast to T1, Rtp did not require FhuA and TonB for infection. The
      46.2-kb genome of phage Rtp encodes 75 open reading frames, 47 of which are
      homologous to phage T1 genes. Like phage T1, phage Rtp encodes a large number of
      small genes at the genome termini that exhibit no sequence similarity to known
      genes. Six predicted genes larger than 300 nucleotides in the highly homologous
      region of Rtp are not found in T1. Two predicted HNH endonucleases are encoded at
      positions different from those in phage T1. The sequence similarity of rtp37, 
      38, -39, -41, -42, and -43 to equally arranged genes of lambdoid phages suggests
      a common tail assembly initiation complex. Protein Rtp43 is homologous to the
      lambda J protein, which determines lambda host specificity. Since the two
      proteins differ most in the C-proximal area, where the binding site to the LamB
      receptor resides in the J protein, we propose that Rtp43 contributes to Rtp host
      specificity. Lipoproteins similar to the predicted lipoprotein Rtp45 are found in
      a number of phages (encoded by cor genes) in which they prevent superinfection by
      inactivating the receptors. We propose that, similar to the proposed function of
      the phage T5 lipoprotein, Rtp45 prevents inactivation of Rtp by adsorption to its
      receptor during cells lysis. Rtp52 is a putative transcriptional regulator, for
      which 10 conserved inverted repeats were identified upstream of genes in the Rtp
      genome. In contrast, the much larger E. coli genome has only one such repeat
      sequence.

PMID- 16452427
TI  - Lethal mutations in the isoprenoid pathway of Salmonella enterica.
AB  - Essential isoprenoid compounds are synthesized using the 2-C-methyl-D-erythritol
      4-phosphate (MEP) pathway in many gram-negative bacteria, some gram-positive
      bacteria, some apicomplexan parasites, and plant chloroplasts. The alternative
      mevalonate pathway is found in archaea and eukaryotes, including cytosolic
      biosynthesis in plants. The existence of orthogonal essential pathways in
      eukaryotes and bacteria makes the MEP pathway an attractive target for the
      development of antimicrobial agents. A system is described for identifying
      mutations in the MEP pathway of Salmonella enterica serovar Typhimurium. Using
      this system, point mutations induced by diethyl sulfate were found in the all
      genes of the essential MEP pathway and also in genes involved in uptake of
      methylerythritol. Curiously, none of the MEP pathway genes could be identified in
      the same parent strain by transposon mutagenesis, despite extensive searches. The
      results complement the biochemical and bioinformatic approaches to the
      elucidation of the genes involved in the MEP pathway and also identify key
      residues for activity in the enzymes of the pathway.

PMID- 16452428
TI  - Quorum sensing in Yersinia enterocolitica controls swimming and swarming
      motility.
AB  - The Yersinia enterocolitica LuxI homologue YenI directs the synthesis of N-3
      (oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) and N-hexanoylhomoserine lactone
      (C6-HSL). In a Y. enterocolitica yenI mutant, swimming motility is temporally
      delayed while swarming motility is abolished. Since both swimming and swarming
      are flagellum dependent, we purified the flagellin protein from the parent and
      yenI mutant. Electrophoresis revealed that in contrast to the parent strain, the
      yenI mutant grown for 17 h at 26 degrees C lacked the 45-kDa flagellin protein
      FleB. Reverse transcription-PCR indicated that while mutation of yenI had no
      effect on yenR, flhDC (the motility master regulator) or fliA (the flagellar
      sigma factor) expression, fleB (the flagellin structural gene) was down
      regulated. Since 3-oxo-C6-HSL and C6-HSL did not restore swimming or swarming in
      the yenI mutant, we reexamined the N-acylhomoserine lactone (AHL) profile of Y.
      enterocolitica. Using AHL biosensors and mass spectrometry, we identified three
      additional AHLs synthesized via YenI: N-(3-oxodecanoyl)homoserine lactone, N-(3
      oxododecanoyl)homoserine lactone (3-oxo-C12-HSL), and N-(3
      oxotetradecanoyl)homoserine lactone. However, none of the long-chain AHLs either
      alone or in combination with the short-chain AHLs restored swarming or swimming
      in the yenI mutant. By investigating the transport of radiolabeled 3-oxo-C12-HSL
      and by introducing an AHL biosensor into the yenI mutant we demonstrate that the
      inability of exogenous AHLs to restore motility to the yenI mutant is not related
      to a lack of AHL uptake. However, both AHL synthesis and motility were restored
      by complementation of the yenI mutant with a plasmid-borne copy of yenI.

PMID- 16452429
TI  - Genetic diversity in Mycobacterium ulcerans isolates from Ghana revealed by a
      newly identified locus containing a variable number of tandem repeats.
AB  - The molecular typing methods used so far for Mycobacterium ulcerans isolates have
      not been able to identify genetic differences among isolates from Africa. This
      apparent lack of genetic diversity among M. ulcerans isolates is indicative of a
      clonal population structure. We analyzed the genetic diversity of 72 African
      isolates, including 57 strains from Ghana, by variable number of tandem repeat
      (VNTR) typing based on a newly identified polymorphic locus designated ST1 and
      the previously described locus MIRU 1. Three different genotypes were found in
      Ghana, demonstrating for the first time the genetic diversity of M. ulcerans in
      an African country. While the ST1/MIRU 1 allele combination BD/BAA seems to
      dominate in Africa, it was only rarely found in isolates from Ghana, where the
      combination BD/B was dominant and observed in all districts studied. A third
      variant genotype (C/BAA) was found only in the Amansie-West district. The results
      indicate that new genetic variants of M. ulcerans emerged and spread within Ghana
      and support the potential of VNTR-based typing for genotyping of M. ulcerans.

PMID- 16452430
TI  - Roles of charged residues of rotor and stator in flagellar rotation: comparative
      study using H+-driven and Na+-driven motors in Escherichia coli.
AB  - In Escherichia coli, rotation of the flagellar motor has been shown to depend
      upon electrostatic interactions between charged residues of the stator protein
      MotA and the rotor protein FliG. These charged residues are conserved in the Na+
      driven polar flagellum of Vibrio alginolyticus, but mutational studies in V.
      alginolyticus suggested that they are relatively unimportant for motor rotation.
      The electrostatic interactions detected in E. coli therefore might not be a
      general feature of flagellar motors, or, alternatively, the V. alginolyticus
      motor might rely on similar interactions but incorporate additional features that
      make it more robust against mutation. Here, we have carried out a comparative
      study of chimeric motors that were resident in E. coli but engineered to use V.
      alginolyticus stator components, rotor components, or both. Charged residues in
      the V. alginolyticus rotor and stator proteins were found to be essential for
      motor rotation when the proteins functioned in the setting of the E. coli motor.
      Patterns of synergism and suppression in rotor/stator double mutants indicate
      that the V. alginolyticus proteins interact in essentially the same way as their
      counterparts in E. coli. The robustness of the rotor-stator interface in V.
      alginolyticus is in part due to the presence of additional charged residues in
      PomA but appears mainly due to other factors, because an E. coli motor using both
      rotor and stator components from V. alginolyticus remained sensitive to mutation.
      Motor function in V. alginolyticus may be enhanced by the proteins MotX and MotY.

PMID- 16452432
TI  - ParABS systems of the four replicons of Burkholderia cenocepacia: new chromosome
      centromeres confer partition specificity.
AB  - Most bacterial chromosomes carry an analogue of the parABS systems that govern
      plasmid partition, but their role in chromosome partition is ambiguous. parABS
      systems might be particularly important for orderly segregation of multipartite
      genomes, where their role may thus be easier to evaluate. We have characterized
      parABS systems in Burkholderia cenocepacia, whose genome comprises three
      chromosomes and one low-copy-number plasmid. A single parAB locus and a set of
      ParB-binding (parS) centromere sites are located near the origin of each
      replicon. ParA and ParB of the longest chromosome are phylogenetically similar to
      analogues in other multichromosome and monochromosome bacteria but are distinct
      from those of smaller chromosomes. The latter form subgroups that correspond to
      the taxa of their hosts, indicating evolution from plasmids. The parS sites on
      the smaller chromosomes and the plasmid are similar to the "universal" parS of
      the main chromosome but with a sequence specific to their replicon. In an
      Escherichia coli plasmid stabilization test, each parAB exhibits partition
      activity only with the parS of its own replicon. Hence, parABS function is based
      on the independent partition of individual chromosomes rather than on a single
      communal system or network of interacting systems. Stabilization by the smaller
      chromosome and plasmid systems was enhanced by mutation of parS sites and a
      promoter internal to their parAB operons, suggesting autoregulatory mechanisms.
      The small chromosome ParBs were found to silence transcription, a property
      relevant to autoregulation.

PMID- 16452431
TI  - The genome sequence of the obligately chemolithoautotrophic, facultatively
      anaerobic bacterium Thiobacillus denitrificans.
AB  - The complete genome sequence of Thiobacillus denitrificans ATCC 25259 is the
      first to become available for an obligately chemolithoautotrophic, sulfur
      compound-oxidizing, beta-proteobacterium. Analysis of the 2,909,809-bp genome
      will facilitate our molecular and biochemical understanding of the unusual
      metabolic repertoire of this bacterium, including its ability to couple
      denitrification to sulfur-compound oxidation, to catalyze anaerobic, nitrate
      dependent oxidation of Fe(II) and U(IV), and to oxidize mineral electron donors.
      Notable genomic features include (i) genes encoding c-type cytochromes totaling 1
      to 2 percent of the genome, which is a proportion greater than for almost all
      bacterial and archaeal species sequenced to date, (ii) genes encoding two
      [NiFe]hydrogenases, which is particularly significant because no information on
      hydrogenases has previously been reported for T. denitrificans and hydrogen
      oxidation appears to be critical for anaerobic U(IV) oxidation by this species,
      (iii) a diverse complement of more than 50 genes associated with sulfur-compound
      oxidation (including sox genes, dsr genes, and genes associated with the AMP
      dependent oxidation of sulfite to sulfate), some of which occur in multiple (up
      to eight) copies, (iv) a relatively large number of genes associated with
      inorganic ion transport and heavy metal resistance, and (v) a paucity of genes
      encoding organic-compound transporters, commensurate with obligate
      chemolithoautotrophy. Ultimately, the genome sequence of T. denitrificans will
      enable elucidation of the mechanisms of aerobic and anaerobic sulfur-compound
      oxidation by beta-proteobacteria and will help reveal the molecular basis of this
      organism's role in major biogeochemical cycles (i.e., those involving sulfur,
      nitrogen, and carbon) and groundwater restoration.

PMID- 16452433
TI  - The bifunctional FtsK protein mediates chromosome partitioning and cell division
      in Caulobacter.
AB  - Bacterial chromosome partitioning and cell division are tightly connected
      cellular processes. We show here that the Caulobacter crescentus FtsK protein
      localizes to the division plane, where it mediates multiple functions involved in
      chromosome segregation and cytokinesis. The first 258 amino acids of the N
      terminus are necessary and sufficient for targeting the protein to the division
      plane. Furthermore, the FtsK N terminus is required to either assemble or
      maintain FtsZ rings at the division plane. The FtsK C terminus is essential in
      Caulobacter and is involved in maintaining accurate chromosome partitioning. In
      addition, the C-terminal region of FtsK is required for the localization of the
      topoisomerase IV ParC subunit to the replisome to facilitate chromosomal
      decatenation prior to cell division. These results suggest that the
      interdependence between chromosome partitioning and cell division in Caulobacter
      is mediated, in part, by the FtsK protein.

PMID- 16452434
TI  - Solution structure of a low-molecular-weight protein tyrosine phosphatase from
      Bacillus subtilis.
AB  - The low-molecular-weight (LMW) protein tyrosine phosphatases (PTPs) exist
      ubiquitously in prokaryotes and eukaryotes and play important roles in cellular
      processes. We report here the solution structure of YwlE, an LMW PTP identified
      from the gram-positive bacteria Bacillus subtilis. YwlE consists of a twisted
      central four-stranded parallel beta-sheet with seven alpha-helices packing on
      both sides. Similar to LMW PTPs from other organisms, the conformation of the
      YwlE active site is favorable for phosphotyrosine binding, indicating that it may
      share a common catalytic mechanism in the hydrolysis of phosphate on tyrosine
      residue in proteins. Though the overall structure resembles that of the
      eukaryotic LMW PTPs, significant differences were observed around the active
      site. Residue Asp115 is likely interacting with residue Arg13 through
      electrostatic interaction or hydrogen bond interaction to stabilize the
      conformation of the active cavity, which may be a unique character of bacterial
      LMW PTPs. Residues in the loop region from Phe40 to Thr48 forming a wall of the
      active cavity are more flexible than those in other regions. Ala41 and Gly45 are
      located near the active cavity and form a noncharged surface around it. These
      unique properties demonstrate that this loop may be involved in interaction with
      specific substrates. In addition, the results from spin relaxation experiments
      elucidate further insights into the mobility of the active site. The solution
      structure in combination with the backbone dynamics provides insights into the
      mechanism of substrate specificity of bacterial LMW PTPs.

PMID- 16452435
TI  - A mobile quorum-sensing system in Serratia marcescens.
AB  - Quorum-sensing systems that have been widely identified in bacteria play
      important roles in the regulation of bacterial multicellular behavior by which
      bacteria sense population density to control various biological functions,
      including virulence. One characteristic of the luxIR quorum-sensing genes is
      their diverse and discontinuous distribution among proteobacteria. Here we report
      that the spnIR quorum-sensing system identified in the enterobacterium Serratia
      marcescens strain SS-1 is carried in a transposon, TnTIR, which has common
      characteristics of Tn3 family transposons and is mobile between chromosomes and
      plasmids of different enterobacterial hosts. SpnIR functions in the new host and
      was shown to negatively regulate the TnTIR transposition frequency. This finding
      may help reveal the horizontal transfer and evolutionary mechanism of quorum
      sensing genes and alter the way that we perceive regulation of bacterial
      multicellular behavior.

PMID- 16452437
TI  - In the Bacillus stearothermophilus DnaB-DnaG complex, the activities of the two
      proteins are modulated by distinct but overlapping networks of residues.
AB  - We demonstrate the primase activity of Bacillus stearothermophilus DnaG and show
      that it initiates at 3'-ATC-5' and 3'-ATT-5' sites synthesizing primers that are
      22 or 23 nucleotides long. In the presence of the helicase DnaB the size
      distribution of primers is different, and a range of additional smaller primers
      are also synthesized. Nine residues from the N- and C-terminal domains of DnaB,
      as well as its linker region, have been reported previously to affect this
      interaction. In Bacillus stearothermophilus only three residues from the linker
      region (I119 and I125) and the N-terminal domain (Y88) of DnaB have been shown
      previously to have direct structural importance, and I119 and I125 mediate DnaG
      induced effects on DnaB activity. The functions of the other residues (L138,
      T191, E192, R195, and M196) are still a mystery. Here we show that the E15A,
      Y88A, and E15A Y88A mutants bind DnaG but are not able to modulate primer size,
      whereas the R195A M196A mutant inhibited the primase activity. Therefore, four of
      these residues, E15 and Y88 (N-terminal domain) and R195 and M196 (C-terminal
      domain), mediate DnaB-induced effects on DnaG activity. Overall, the data suggest
      that the effects of DnaB on DnaG activity and vice versa are mediated by distinct
      but overlapping networks of residues.

PMID- 16452436
TI  - Assembly of distinct pilus structures on the surface of Corynebacterium
      diphtheriae.
AB  - Different surface organelles contribute to specific interactions of a pathogen
      with host tissues or infectious partners. Multiple pilus gene clusters
      potentially encoding different surface structures have been identified in several
      gram-positive bacterial genomes sequenced to date, including actinomycetales,
      clostridia, corynebacteria, and streptococci. Corynebacterium diphtheriae has
      been shown to assemble a pilus structure, with sortase SrtA essential for the
      assembly of a major subunit SpaA and two minor proteins, SpaB and SpaC. We report
      here the characterization of a second pilus consisting of SpaD, SpaE, and SpaF,
      of which SpaD and SpaE form the pilus shaft and SpaF may be located at the pilus
      tip. The structure of the SpaDEF pilus contains no SpaABC pilins as detected by
      immunoelectron microscopy. Neither deletion of spaA nor sortase srtA abolishes
      SpaDEF pilus formation. The assembly of the SpaDEF pilus requires specific
      sortases located within the SpaDEF pilus gene cluster. Although either sortase
      SrtB or SrtC is sufficient to polymerize SpaDF, the incorporation of SpaE into
      the SpaD pili requires sortase SrtB. In addition, an alanine in place of the
      lysine of the SpaD pilin motif abrogates pilus polymerization. Thus, SpaD, SpaE,
      and SpaF constitute a different pilus structure that is independently assembled
      and morphologically distinct from the SpaABC pili and possibly other pili of C.
      diphtheriae.

PMID- 16452438
TI  - Influence of CrgA on assembly of the cell division protein FtsZ during
      development of Streptomyces coelicolor.
AB  - The product of the crgA gene of Streptomyces coelicolor represents a novel family
      of small proteins. A single orthologous gene is located close to the origin of
      replication of all fully sequenced actinomycete genomes and borders a conserved
      gene cluster implicated in cell growth and division. In S. coelicolor, CrgA is
      important for coordinating growth and cell division in sporogenic hyphae. In this
      study, we demonstrate that CrgA is an integral membrane protein whose peak
      expression is coordinated with the onset of development of aerial hyphae. The
      protein localizes to discrete foci away from growing hyphal tips. Upon
      overexpression, CrgA localizes to apical syncytial cells of aerial hyphae and
      inhibits the formation of productive cytokinetic rings of the bacterial tubulin
      homolog FtsZ, leading to proteolytic turnover of this major cell division
      determinant. In the absence of known prokaryotic cell division inhibitors in
      actinomycetes, CrgA may have an important conserved function influencing Z-ring
      formation in these bacteria.

PMID- 16452439
TI  - Genetic and transcriptional analysis of the siderophore malleobactin biosynthesis
      and transport genes in the human pathogen Burkholderia pseudomallei K96243.
AB  - Burkholderia pseudomallei is a gram-negative facultative intracellular pathogen
      that causes melioidosis, an invasive disease of humans and animals. To address
      the response of this bacterium to iron-limiting conditions, we first performed a
      global transcriptional analysis of RNA extracted from bacteria grown under iron
      limiting and iron-rich conditions by microarrays. We focused our study on those
      open reading frames (ORFs) induced under iron limitation, which encoded predicted
      proteins that could be involved in the biosynthesis and uptake of the siderophore
      malleobactin. We purified this siderophore and determined that it consisted of at
      least three compounds with different molecular weights. We demonstrated that ORFs
      BPSL1776 and BPSL1774, designated mbaA and mbaF, respectively, are involved in
      the biosynthesis of malleobactin, while BPSL1775, named fmtA, is involved in its
      transport. These genes are in an operon with two other ORFs (mbaJ and mbaI) whose
      transcription is under the control of MbaS, a protein that belongs to the
      extracytoplasmic function sigma factors. Interestingly, the transcription of the
      mbaA, fmtA, and mbaS genes is not controlled by the availability of the
      siderophore malleobactin.

PMID- 16452440
TI  - Tetrapyrrole biosynthesis in Rhodobacter capsulatus is transcriptionally
      regulated by the heme-binding regulatory protein, HbrL.
AB  - We demonstrate that the expression of hem genes in Rhodobacter capsulatus is
      transcriptionally repressed in response to the exogenous addition of heme. A high
      copy suppressor screen for regulators of hem gene expression resulted in the
      identification of an LysR-type transcriptional regulator, called HbrL, that
      regulates hem promoters in response to the availability of heme. HbrL is shown to
      activate the expression of hemA and hemZ in the absence of exogenous hemin and
      repress hemB expression in the presence of exogenous hemin. Heterologously
      expressed HbrL apoprotein binds heme b and is purified with bound heme b when
      expressed in the presence of 5-aminolevulinic acid. Electrophoretic gel shift
      analysis demonstrated that HbrL binds the promoter region of hemA, hemB, and hemZ
      as well as its own promoter and that the presence of heme increases the binding
      affinity of HbrL to hemB.

PMID- 16452441
TI  - A Na+:H+ antiporter and a molybdate transporter are essential for arsenite
      oxidation in Agrobacterium tumefaciens.
AB  - Transposon Tn5-B22 mutagenesis was used to identify genetic determinants required
      for arsenite [As(III)] oxidation in an Agrobacterium tumefaciens soil isolate,
      strain 5A. In one mutant, the transposon interrupted modB, which codes for the
      permease component of a high-affinity molybdate transporter. In a second mutant,
      the transposon insertion occurred in mrpB, which is part of a seven-gene operon
      encoding an Mrp-type Na+:H+ antiporter complex. Complementation experiments with
      mod and mrp operons PCR cloned from the genome-sequenced A. tumefaciens strain
      C58 resulted in complementation back to an As(III)-oxidizing phenotype,
      confirming that these genes encode activities essential for As(III) oxidation in
      this strain of A. tumefaciens. As expected, the mrp mutant was extremely
      sensitive to NaCl and LiCl, indicating that the Mrp complex in A. tumefaciens is
      involved in Na+ circulation across the membrane. Gene expression studies (lacZ
      reporter and reverse transcriptase PCR experiments) failed to show evidence of
      transcriptional regulation of the mrp operon in response to As(III) exposure,
      whereas expression of the mod operon was found to be up-regulated by As(III)
      exposure. In each mutant, the loss of As(III)-oxidizing capacity resulted in
      conversion to an arsenate [As(V)]-reducing phenotype. Neither mutant was more
      sensitive to As(III) than the parental strain.

PMID- 16452443
TI  - Unusual extra space at the active site and high activity for acetylated
      hydroxyproline of prolyl aminopeptidase from Serratia marcescens.
AB  - The prolyl aminopeptidase complexes of Ala-TBODA [2-alanyl-5-tert-butyl-(1, 3, 4)
      oxadiazole] and Sar-TBODA [2-sarcosyl-5-tert-butyl-(1, 3, 4)-oxadiazole] were
      analyzed by X-ray crystallography at 2.4 angstroms resolution. Frames of alanine
      and sarcosine residues were well superimposed on each other in the pyrrolidine
      ring of proline residue, suggesting that Ala and Sar are recognized as parts of
      this ring of proline residue by the presence of a hydrophobic proline pocket at
      the active site. Interestingly, there was an unusual extra space at the bottom of
      the hydrophobic pocket where proline residue is fixed in the prolyl
      aminopeptidase. Moreover, 4-acetyloxyproline-betaNA (4-acetyloxyproline beta
      naphthylamide) was a better substrate than Pro-betaNA. Computer docking
      simulation well supports the idea that the 4-acetyloxyl group of the substrate
      fitted into that space. Alanine scanning mutagenesis of Phe139, Tyr149, Tyr150,
      Phe236, and Cys271, consisting of the hydrophobic pocket, revealed that all of
      these five residues are involved significantly in the formation of the
      hydrophobic proline pocket for the substrate. Tyr149 and Cys271 may be important
      for the extra space and may orient the acetyl derivative of hydroxyproline to a
      preferable position for hydrolysis. These findings imply that the efficient
      degradation of collagen fragment may be achieved through an acetylation process
      by the bacteria.

PMID- 16452442
TI  - Complete sequencing and diversity analysis of the enterotoxin-encoding plasmids
      in Clostridium perfringens type A non-food-borne human gastrointestinal disease
      isolates.
AB  - Enterotoxin-producing Clostridium perfringens type A isolates are an important
      cause of food poisoning and non-food-borne human gastrointestinal diseases, e.g.,
      sporadic diarrhea (SPOR) and antibiotic-associated diarrhea (AAD). The
      enterotoxin gene (cpe) is usually chromosomal in food poisoning isolates but
      plasmid-borne in AAD/SPOR isolates. Previous studies determined that type A SPOR
      isolate F5603 has a plasmid (pCPF5603) carrying cpe, IS1151, and the beta2 toxin
      gene (cpb2), while type A SPOR isolate F4969 has a plasmid (pCPF4969) lacking
      cpb2 and IS1151 but carrying cpe and IS1470-like sequences. By completely
      sequencing these two cpe plasmids, the current study identified pCPF5603 as a
      75.3-kb plasmid carrying 73 open reading frames (ORFs) and pCPF4969 as a 70.5-kb
      plasmid carrying 62 ORFs. These plasmids share an approximately 35-kb conserved
      region that potentially encodes virulence factors and carries ORFs found on the
      conjugative transposon Tn916. The 34.5-kb pCPF4969 variable region contains ORFs
      that putatively encode two bacteriocins and a two-component regulator similar to
      VirR/VirS, while the approximately 43.6-kb pCPF5603 variable region contains a
      functional cpb2 gene and several metabolic genes. Diversity studies indicated
      that other type A plasmid cpe+/IS1151 SPOR/AAD isolates carry a pCPF5603-like
      plasmid, while other type A plasmid cpe+/IS1470-like SPOR/AAD isolates carry a
      pCPF4969-like plasmid. Tn916-related ORFs similar to those in pCPF4969 (known to
      transfer conjugatively) were detected in the cpe plasmids of other type A
      SPOR/AAD isolates, as well as in representative C. perfringens type B to D
      isolates carrying other virulence plasmids, possibly suggesting that most or all
      C. perfringens virulence plasmids transfer conjugatively.

PMID- 16452444
TI  - The crystal structure of the zinc phosphodiesterase from Escherichia coli
      provides insight into function and cooperativity of tRNase Z-family proteins.
AB  - The elaC gene product from Escherichia coli, ZiPD, is a 3' tRNA-processing
      endonuclease belonging to the tRNase Z family of enzymes that have been
      identified in a wide variety of organisms. In contrast to the elaC homologue from
      Bacillus subtilis, E. coli elaC is not essential for viability, and although both
      enzymes process only precursor tRNA (pre-tRNA) lacking a CCA triplet at the 3'
      end in vitro, the physiological role of ZiPD remains enigmatic because all pre
      tRNA species in E. coli are transcribed with the CCA triplet. We present the
      first crystal structure of ZiPD determined by multiple anomalous diffraction at a
      resolution of 2.9 A. This structure shares many features with the tRNase Z
      enzymes from B. subtilis and Thermotoga maritima, but there are distinct
      differences in metal binding and overall domain organization. Unlike the
      previously described homologous structures, ZiPD dimers display crystallographic
      symmetry and fully loaded metal sites. The ZiPD exosite is similar to that of the
      B. subtilis enzyme structurally, but its position with respect to the protein
      core differs substantially, illustrating its ability to act as a clamp in binding
      tRNA. Furthermore, the ZiPD crystal structure presented here provides insight
      into the enzyme's cooperativity and assists the ongoing attempt to elucidate the
      physiological function of this protein.

PMID- 16452445
TI  - NnrA is required for full virulence and regulates several Brucella melitensis
      denitrification genes.
AB  - We identified two regulators of denitrification genes in Brucella melitensis 16M:
      NarR, which regulates the nitrate reductase (nar) operon, and NnrA, which is
      involved in the expression of the last three reductases of the denitrification
      pathway (nirK, norB, and nosZ). NnrA is required for virulence in mice and for
      intracellular resistance to nitric oxide.

PMID- 16452446
TI  - Apyrase, the product of the virulence plasmid-encoded phoN2 (apy) gene of
      Shigella flexneri, is necessary for proper unipolar IcsA localization and for
      efficient intercellular spread.
AB  - The role in virulence of the Shigella flexneri ospB-phoN2 operon has been
      evaluated. Here we confirm that OspB is an effector and show that apyrase, the
      product of phoN2, may be a virulence factor, since it is required for efficient
      intercellular spreading. Apyrase may be important in a deoxynucleoside
      triphosphate-hydrolyzing activity-independent manner, suggesting that it may act
      as an interaction partner in the process of IcsA localization.

PMID- 16452448
TI  - Transcriptome profiling of Shewanella oneidensis gene expression following
      exposure to acidic and alkaline pH.
AB  - The molecular response of Shewanella oneidensis MR-1 to variations in
      extracellular pH was investigated based on genomewide gene expression profiling.
      Microarray analysis revealed that cells elicited both general and specific
      transcriptome responses when challenged with environmental acid (pH 4) or base
      (pH 10) conditions over a 60-min period. Global responses included the
      differential expression of genes functionally linked to amino acid metabolism,
      transcriptional regulation and signal transduction, transport, cell membrane
      structure, and oxidative stress protection. Response to acid stress included the
      elevated expression of genes encoding glycogen biosynthetic enzymes, phosphate
      transporters, and the RNA polymerase sigma-38 factor (rpoS), whereas the
      molecular response to alkaline pH was characterized by upregulation of nhaA and
      nhaR, which are predicted to encode an Na+/H+ antiporter and transcriptional
      activator, respectively, as well as sulfate transport and sulfur metabolism
      genes. Collectively, these results suggest that S. oneidensis modulates multiple
      transporters, cell envelope components, and pathways of amino acid consumption
      and central intermediary metabolism as part of its transcriptome response to
      changing external pH conditions.

PMID- 16452447
TI  - A eukaryotic-type serine/threonine protein kinase is required for biofilm
      formation, genetic competence, and acid resistance in Streptococcus mutans.
AB  - We report an operon encoding a eukaryotic-type serine/threonine protein kinase
      (STPK) and its cognate phosphatase (STPP) in Streptococcus mutans. Mutation of
      the gene encoding the STPK produced defects in biofilm formation, genetic
      competence, and acid resistance, determinants important in caries pathogenesis.

PMID- 16452449
TI  - Identification of a gene encoding a functional reverse transcriptase within a
      highly variable locus in the P2-like coliphages.
AB  - The P2-like coliphages are highly similar; the structural genes show at least 96%
      identity. However, at two loci they have genes believed to be horizontally
      transferred. We show that the genetic content at the second loci, the TO region,
      contains six completely different sequences with high AT contents and with
      different open reading frames. The product of one of them exhibits reverse
      transcriptase activity and blocks infection of phage T5.

PMID- 16452450
TI  - Global transcriptome analysis of Staphylococcus aureus response to hydrogen
      peroxide.
AB  - Staphylococcus aureus responds with protective strategies against phagocyte
      derived reactive oxidants to infect humans. Herein, we report the transcriptome
      analysis of the cellular response of S. aureus to hydrogen peroxide-induced
      oxidative stress. The data indicate that the oxidative response includes the
      induction of genes involved in virulence, DNA repair, and notably, anaerobic
      metabolism.

PMID- 16452451
TI  - MurQ Etherase is required by Escherichia coli in order to metabolize anhydro-N
      acetylmuramic acid obtained either from the environment or from its own cell
      wall.
AB  - MurQ is an N-acetylmuramic acid-phosphate (MurNAc-P) etherase that converts
      MurNAc-P to N-acetylglucosamine-phosphate and is essential for growth on MurNAc
      as the sole source of carbon (T. Jaegar, M. Arsic, and C. Mayer, J. Biol. Chem.
      280:30100-30106, 2005). Here we show that MurQ is the only MurNAc-P etherase in
      Escherichia coli and that MurQ and AnmK kinase are required for utilization of
      anhydro-MurNAc derived either from cell wall murein or imported from the medium.

PMID- 16452452
TI  - Repressor of phage 16-3 with altered binding specificity indicates spatial
      differences in repressor-operator complexes.
AB  - The C repressor protein of phage 16-3, which is required for establishing and
      maintaining lysogeny, recognizes structurally different operators which differ by
      2 bp in the length of the spacer between the conserved palindromic sequences. A
      "rotationally flexible protein homodimers" model has been proposed in order to
      explain the conformational adaptivity of the 16-3 repressor. In this paper, we
      report on the isolation of a repressor mutant with altered binding specificity
      which was used to identify a residue-base pair contact and to monitor the spatial
      relationship of the recognition helix of C repressor to the contacting major
      groove of DNA within the two kinds of repressor-operator complexes. Our results
      indicate spatial differences at the interface which may reflect different docking
      arrangements in recognition of the structurally different operators by the 16-3
      repressor.

PMID- 16452453
TI  - Regulation of reconstituted high density lipoprotein structure and remodeling by
      apolipoprotein E.
AB  - Apolipoprotein E (apoE) enters the plasma as a component of discoidal HDL and is
      subsequently incorporated into spherical HDL, most of which contain apoE as the
      sole apolipoprotein. This study investigates the regulation, origins, and
      structure of spherical, apoE-containing HDLs and their remodeling by cholesteryl
      ester transfer protein (CETP). When the ability of discoidal reconstituted high
      density lipoprotein (rHDL) containing apoE2 [(E2)rHDL], apoE3 [(E3)rHDL], or
      apoE4 [(E4)rHDL] as the sole apolipoprotein to act as substrates for LCAT were
      compared with that of discoidal rHDL containing apoA-I [(A-I)rHDL], the rate of
      cholesterol esterification was (A-I)rHDL >> (E2)rHDL approximately (E3)rHDL >
      (E4)rHDL. LCAT also had a higher affinity for discoidal (A-I)rHDL than for the
      apoE-containing rHDL. When the discoidal rHDLs were incubated with LCAT and LDL,
      the resulting spherical (E2)rHDL, (E3)rHDL, and (E4)rHDL were larger than, and
      structurally distinct from, spherical (A-I)rHDL. Incubation of the apoE
      containing spherical rHDL with CETP and Intralipid(R) generated large fusion
      products without the dissociation of apoE, whereas the spherical (A-I)rHDLs were
      remodeled into small particles with the formation of lipid-poor apoA-I. In
      conclusion, i) apoE activates LCAT less efficiently than apoA-I; ii) apoE
      containing spherical rHDLs are structurally distinct from spherical (A-I)rHDL;
      and iii) the CETP-mediated remodeling of apoE-containing spherical rHDL differs
      from that of spherical (A-I)rHDL.

PMID- 16452454
TI  - Cross-modal interactions between olfaction and touch.
AB  - We report two experiments designed to investigate the nature of any cross-modal
      interactions between olfactory and tactile information processing. In Experiment
      1, we assessed the influence of olfactory cues on the tactile perception of
      fabric softness using computer-controlled stimulus presentation. The results
      showed that participants rated fabric swatches as feeling significantly softer
      when presented with a lemon odor than when presented with an animal-like odor,
      demonstrating that olfactory cues can modulate tactile perception. In Experiment
      2, we assessed whether this modulatory effect varied as a function of the
      particular odors being used and/or of the spatial coincidence between the
      olfactory and tactile stimuli. The results replicated those reported in
      Experiment 1 thus further supporting the claim that people's rating of tactile
      stimuli can be modulated by the presence of an odor. Taken together, the results
      of the two experiments reported here support the existence of a cross-modal
      interaction between olfaction and touch.

PMID- 16452455
TI  - Characterization and long-term maintenance of rat taste cells in culture.
AB  - Taste cells have a limited life span and are replaced from a basal cell
      population, although the specific factors involved in this process are not well
      known. Short- and long-term cultures of other sensory cells have facilitated
      efforts to understand the signals involved in proliferation, differentiation, and
      senescence, yet few studies have reported successful primary culture protocols
      for taste cells. Furthermore, no studies have demonstrated both proliferation and
      differentiation in vitro. In this study, we have developed an in vitro culture
      system to maintain and utilize rat primary taste cells for more than 2 months
      without losing key molecular and biochemical features. Gustducin, phospholipase C
      beta2 (PLC-beta2), T1R3, and T2R5 mRNA were detected in the cultured cells by
      reverse transcriptase-polymerase chain reaction. Western blot analysis
      demonstrated gustducin and PLC-beta2 expression in the same samples, which was
      confirmed by immunocytochemistry. Labeling with bromo-2-deoxyuridine (BrdU)
      demonstrated proliferation, and a subset of BrdU-labeled cells were also
      immunoreactive for either gustducin or PLC-beta2, indicating differentiation of
      newly generated cells in vitro. Cultured cells also exhibited increases in
      intracellular calcium in response to several taste stimuli. These results
      indicate that taste cells from adult rats can be generated and maintained under
      the described conditions for at least 2 months. This system will enable further
      studies of the processes involved in proliferation, differentiation, and function
      of mammalian taste receptor cells in an in vitro preparation.

PMID- 16452456
TI  - Stanniocalcin (STC) in the endometrial glands of the ovine uterus: regulation by
      progesterone and placental hormones.
AB  - Stanniocalcin (STC) is a hormone in fish that regulates calcium levels. Mammals
      have two orthologs of STC with roles in calcium and phosphate metabolism and
      perhaps cell differentiation. In the kidney and gut, STC regulates calcium and
      phosphate homeostasis. In the mouse uterus, Stc1 increases in the mesometrial
      decidua during implantation. These studies determined the effects of pregnancy
      and related hormones on STC expression in the ovine uterus. In Days 10-16 cyclic
      and pregnant ewes, STC1 mRNA was not detected in the uterus. Intriguingly, STC1
      mRNA appeared on Day 18 of pregnancy, specifically in the endometrial glands,
      increased from Day 18 to Day 80, and remained abundant to Day 120 of gestation.
      STC1 mRNA was not detected in the placenta, whereas STC2 mRNA was detected at low
      abundance in conceptus trophectoderm and endometrial glands during later
      pregnancy. Immunoreactive STC1 protein was detected predominantly in the
      endometrial glands after Day 16 of pregnancy and in areolae that transport
      uterine gland secretions across the placenta. In ovariectomized ewes, long-term
      progesterone therapy induced STC1 mRNA. Although interferon tau had no effect on
      endometrial STC1, intrauterine infusions of ovine placental lactogen (PL)
      increased endometrial gland STC1 mRNA abundance in progestinized ewes. These
      studies demonstrate that STC1 is induced by progesterone and increased by a
      placental hormone (PL) in endometrial glands of the ovine uterus during conceptus
      (embryo/fetus and extraembryonic membranes) implantation and placentation.
      Western blot analyses revealed the presence of a 25-kDa STC1 protein in the
      endometrium, uterine luminal fluid, and allantoic fluid. The data suggest that
      STC1 secreted by the endometrial glands is transported into the fetal circulation
      and allantoic fluid, where it is hypothesized to regulate growth and
      differentiation of the fetus and placenta, by placental areolae.

PMID- 16452457
TI  - Sexually dimorphic regulation of inhibin beta B in establishing gonadal
      vasculature in mice.
AB  - Sexually dimorphic differentiation of gonads is accomplished through balanced
      interactions between positive and negative regulators. One of the earliest
      features of gonadal differentiation is the divergent patterning of the
      vasculature. A male-specific coelomic vessel develops on the anterior to
      posterior of the XY gonad, whereas this vessel is absent in XX gonads. It is
      postulated that the testis-determining gene Sry controls formation of the
      coelomic vessel, but the exact molecular mechanism remains unknown. Here we
      reveal a novel role for inhibin beta B in establishing sex-specific gonad
      vasculature. In the testis, inhibin beta B contributes to proper formation of the
      coelomic vessel, a male-specific artery critical for testis development and,
      later in development, hormone transportation. On the other hand, in the ovary,
      inhibin beta B is repressed by WNT4 and its downstream target follistatin,
      leading to the absence of the coelomic vessel. When either Wnt4 or follistatin
      was inactivated, the coelomic vessel appeared ectopically in the XX ovary.
      However, when inhibin beta B was also removed in either the Wnt4-null or
      follistatin-null background, normal ovarian development was restored and no
      coelomic vessel was found. Our results indicate that the sex-specific formation
      of the coelomic vessel is established by positive components in the testis as
      well as an antagonizing pathway from the ovary. Inhibin beta B is strategically
      positioned at the intersection of these opposing pathways.

PMID- 16452458
TI  - Multiplicity of progesterone's actions and receptors in the mammalian ovary.
AB  - This minireview summarizes the role that progesterone (P4) plays in regulating
      granulosa and luteal cell function. These actions include the stimulation of P4
      synthesis and the inhibition of estrogen synthesis, mitosis, and apoptosis. P4
      also plays a key role in the ovulatory process. Although P4's actions are well
      documented, the mechanism or mechanisms that mediate all of these actions have
      not been defined. In addition to P4-induced gene transcription that is mediated
      by the nuclear P4 receptors (PGR-A and PGR-B), three other receptor/signal
      transduction pathways could account for P4's intraovarian actions. These pathways
      could be mediated by 1) the PGR localizing at or near the plasma membrane and
      activating SRC family kinases, 2) a membrane progestin receptor that responds to
      P4 by lowering intracellular cAMP and increasing MAPK 3/1 activity, and 3) a
      membrane receptor complex composed of serpine 1 mRNA binding protein (also known
      as PAIRBP1 or RDA288) and progesterone receptor membrane component 1. Ligand
      activation of this complex likely leads to an increase in protein kinase G
      activity, the maintenance of low basal intracellular free calcium, and the
      inhibition of granulosa and luteal cell mitosis and apoptosis. Given the
      complexity of P4's actions within the ovary, it is likely that all of these
      receptor/signal transduction pathways influence some aspect of ovarian function
      with the specific P4 response dependent on 1) the expression pattern of these
      putative P4 receptors, 2) the P4 binding affinity of each receptor system, and 3)
      the amount of available P4.

PMID- 16452459
TI  - Effect of steroid milieu on gonadotropin-releasing hormone-1 neuron firing
      pattern and luteinizing hormone levels in male mice.
AB  - GnRH neuronal function is regulated by gonadal hormone feedback. In males,
      testosterone can act directly or be converted to either dihydrotestosterone (DHT)
      or estradiol (E2). We examined central steroid feedback by recording firing of
      green fluorescent protein (GFP)-identified GnRH neurons in brain slices from male
      mice that were intact, castrated, or castrated and treated with implants
      containing DHT, E2, or E2 + DHT. Castration increased LH levels. DHT or E2 alone
      partially suppressed LH, whereas E2 + DHT reduced LH to intact levels. Despite
      the inhibitory actions on LH, the combination of E2 + DHT increased GnRH neuron
      activity relative to other treatments, reflected in mean firing rate, amplitude
      of peaks in firing rate, and area under the curve of firing rate vs. time.
      Cluster8 was used to identify peaks in firing activity that may be correlated
      with hormone release. Castration increased the frequency of peaks in firing rate.
      Treatment with DHT failed to reduce frequency of these peaks. In contrast,
      treatment with E2 reduced peak frequency to intact levels. The frequency of peaks
      in firing rate was intermediate in animals treated with E2 + DHT, perhaps
      suggesting the activating effects of this combination partially counteracts the
      inhibitory actions of E2. These data indicate that E2 mediates central negative
      feedback in males primarily by affecting the pattern of GnRH neuron activity, and
      that androgens combined with estrogens have a central activating effect on GnRH
      neurons. The negative feedback induced by E2 + DHT to restore LH to intact levels
      may mask an excitatory central effect of this combination.

PMID- 16452460
TI  - Developmental effects of sublethal mitochondrial injury in mouse oocytes.
AB  - Mitochondrial dysfunction may be acquired or inherited by oocytes without
      detectable morphological abnormalities. This pathology may account for some
      examples of unexplained pregnancy loss in women following transfer of
      morphologically normal in vitro fertilization (IVF) embryos. The present study
      was intended to determine whether sublethal mitochondrial injury in mouse oocytes
      before IVF negatively affects pre- and postimplantation development, and to
      further define the latency of developmental compromise in relation to aberrant
      mitochondrial metabolism. Mature mouse oocytes were loaded with the mitochondrial
      fluorophore rhodamine-123 and photosensitized for 20 sec, a duration previously
      found to permit preimplantation embryo development to the blastocyst stage and so
      deemed "sublethal." This treatment resulted in some aberrations in cytoplasmic
      patterning of organelles, but did not inhibit zygote mitochondrial metabolism.
      Blastocyst development following IVF was not significantly inhibited following
      sublethal oocyte photosensitization; however, a decrease in trophectoderm cell
      numbers was observed relative to untreated controls. Following intrauterine
      transfer, blastocysts derived from sublethally photosensitized oocytes implanted
      but later aborted at a higher rate, formed fetuses with lower average weights,
      and, in rare cases, formed abnormal fetuses relative to controls.
      Photosensitization for more prolonged durations resulted in failed fertilization
      (2 min) and rapid oocyte degeneration (10 min). Therefore, photosensitization
      duration and the consequent degree of mitochondrial dysfunction are negatively
      related to the onset of developmental compromise. Acquired low-level
      mitochondrial injury is heritable by the resultant embryos and can cause
      postimplantation developmental compromise that may be relevant to some clinically
      observed outcomes following human assisted reproduction strategies, including
      reduced birth weights for gestational age. Future strategies for the detection
      and prevention of mitochondrial dysfunction may assist in improving outcomes for
      some clinically infertile women.

PMID- 16452461
TI  - Maintenance of spermatogenesis by the activated human (Asp567Gly) FSH receptor
      during testicular regression due to hormonal withdrawal.
AB  - The first activating mutation of the FSH receptor (FSHR*D567G) was identified in
      a gonadotropin-deficient hypophysectomized man who exhibited persistent
      spermatogenesis and fertility with only androgen replacement. We have determined
      the ability of FSHR* activity to maintain spermatogenesis and/or steroidogenesis
      during gonadotropin and androgen deprivation in mature transgenic FSHR* mice
      (Tg(Abpa-FSHR*D567G)1Cmal), hereafter referred to as Tg-FSHR* mice. Testes of
      untreated adult Tg-FSHR* males were equivalent in weight to nontransgenic
      controls but exhibited increased total Sertoli cell (24%) and spermatogonia (34%)
      numbers and nonsignificantly elevated spermatocyte-spermatid numbers (13%-17%).
      During sustained GNRH1 agonist treatment that markedly reduced (96%-98%) serum LH
      and testosterone (T) and decreased serum FSH (68%-72%), the testes of GNRH1
      agonist-treated Tg-FSHR* mice remained significantly larger than treated
      nontransgenic controls. After 4 wk of gonadotropin suppression, Sertoli cell
      numbers were reduced in Tg-FSHR* testes to levels comparable with nontransgenic
      testes, whereas spermatogonia numbers were maintained at higher levels relative
      to nontransgenic testes. However, after 8 wk of GNRH1 agonist treatment, the
      total spermatogonia, spermatocyte, or postmeiotic spermatid numbers were reduced
      to equivalent levels in Tg-FSHR* and nontransgenic mice. FSHR* effects were
      further examined in gonadotropin-deficient hypogonadal Gnrh1hpg/Gnrh1hpg (Gnrh1(
      /-)) mice during testicular regression following withdrawal of T after maximal T
      stimulated spermatogenesis. After 6 wk of T withdrawal, spermatogonia,
      spermatocyte, and postmeiotic spermatid numbers in Tg-FSHR* Gnrh1(-/-) testes
      decreased to levels found in untreated Tg-FSHR* Gnrh1(-/-) testes. Basal serum T
      levels in untreated Tg-FSHR* Gnrh1(-/-) males were 2-fold higher than Gnrh1(-/-)
      controls, but following T treatment/withdrawal, serum T and epididymal weights
      declined to basal levels found in nontransgenic Gnrh1(-/-) mice. Therefore, FSHR*
      was unable to sustain circulating T or androgen-dependent epididymal size or
      postmeiotic spermatogenic development. We conclude that FSHR* activity enhances
      Sertoli and spermatogenic development in normal testes but has limited ability to
      maintain spermatogenesis during gonadotropin deficiency, in which the testicular
      response provided by the FSHR*D567G mutation resembled typical FSH-mediated but
      not steroidogenic activity.

PMID- 16452462
TI  - Neither Aurora B activity nor histone H3 phosphorylation is essential for
      chromosome condensation during meiotic maturation of porcine oocytes.
AB  - Aurora kinase B (AURKB) is a chromosomal passenger protein that is essential for
      a number of processes during mitosis. Its activity is regulated by association
      with two other passenger proteins, INCENP and Survivin, and by phosphorylation on
      Thr 232. In this study, we examine expression and phosphorylation on Thr-232 of
      AURKB during meiotic maturation of pig oocytes in correlation with histone H3
      phosphorylation and chromosome condensation. We show that histone H3
      phosphorylation on Ser-10, but not on Ser-28, correlates with progressive
      chromosome condensation during oocyte maturation; Ser-10 phosphorylation starts
      around the time of the breakdown of the nuclear envelope, with the maximal
      activity in metaphase I, whereas Ser-28 phosphorylation does not significantly
      change in maturing oocytes. Treatment of oocytes with 50 microM butyrolactone I
      (BL-I), an inhibitor of cyclin-dependent kinases, or cycloheximide (10
      microg/ml), inhibitor of proteosynthesis, results in a block of oocytes in the
      germinal vesicle stage, when nuclear membrane remains intact; however, condensed
      chromosome fibers or highly condensed chromosome bivalents can be seen in the
      nucleoplasm of BL-I- or cycloheximide-treated oocytes, respectively. In these
      treated oocytes, no or only very weak AURKB activity and phosphorylation of
      histone H3 on Ser-10 can be detected after 27 h of treatment, whereas
      phosphorylation on Ser-28 is not influenced. These results suggest that AURKB
      activity and Ser-10 phosphorylation of histone H3 are not required for chromosome
      condensation in pig oocytes, but might be required for further processing of
      chromosomes during meiosis.

PMID- 16452463
TI  - Expression of porcine endometrial prostaglandin synthase during the estrous cycle
      and early pregnancy, and following endocrine disruption of pregnancy.
AB  - Porcine trophoblast attachment to the uterine surface is associated with
      increased conceptus and endometrial production of prostaglandins. Conceptus
      secretion of estrogen on Day 12 of gestation is important for establishment of
      pregnancy; however, early (Days 9 and 10) exposure to exogenous estrogens results
      in embryonic mortality. Present studies established the temporal and spatial
      pattern of endometrial PTGS1 (prostaglandin-endoperoxide synthase 1) and PTGS2
      expression during the estrous cycle and early pregnancy and determined the effect
      of early estrogen treatment on endometrial PTGS expression in pregnant gilts.
      Endometrial PTGS1 mRNA expression increased 2- to 3-fold after Day 10 of the
      estrous cycle and pregnancy, whereas PTGS2 mRNA expression increased 76-fold
      between Days 5 and 15 of the estrous cycle and pregnancy. Increased expression of
      the PTGS2 transcript was detected in the lumenal epithelium after Day 10 in both
      cyclic and pregnant gilts. There was a 10- and 20-fold increase in endometrial
      PTGS2 protein expression between Days 5 and 18 of the estrous cycle and pregnancy
      respectively. Administration of estrogen on Days 9 and 10 of gestation increased
      endometrial PTGS2 mRNA and protein on Day 10, but decreased PTGS2 mRNA and
      protein in lumenal epithelium (LE) on Day 12 of gestation compared to vehicle
      treated gilts. The present study demonstrates that an increase in uterine
      epithelial PTGS2 expression occurs after Day 10 of the estrous cycle and early
      pregnancy in the pig. The conceptus-independent increase in the uterine LE
      indicates that a novel pathway exists for endometrial induction PTGS2 expression
      before conceptus elongation and attachment to the uterine surface. Epithelial
      expression of PTGS2 may serve as one of the signals for placental attachment and
      embryo survival in the pig. Early administration of estrogen on Days 9 and 10 of
      pregnancy alters endometrial PTGS2 mRNA and protein expression, which may, at
      least in part, represent a mechanism by which endocrine disruption of pregnancy
      causes total embryonic loss during implantation in the pig.

PMID- 16452464
TI  - Visualization of GM1 with cholera toxin B in live epididymal versus ejaculated
      bull, mouse, and human spermatozoa.
AB  - The organization of membrane subdomains in mammalian sperm has recently generated
      controversy, with several reports describing widely differing localization
      patterns for the ganglioside GM1. Using the pentameric B subunit of cholera toxin
      (CTB), we found GM1 to be restricted to the plasma membrane overlying the
      acrosome in the heads of live murine sperm. Interestingly, CTB had minimal
      binding to live bovine and human sperm. To investigate whether this difference in
      GM1 localization was because of species differences or differences between
      collection from the epididymis (mouse) or an ejaculate (bull, human), we examined
      epididymal bovine and human sperm. We found that GM1 localized to the plasma
      membrane overlying the acrosome in sperm from these species. To determine whether
      some component of seminal plasma was interfering with the ability of CTB to
      access GM1, we incubated epididymal mouse sperm with fluid from murine seminal
      vesicles and epididymal bull sperm with bovine seminal plasma. This treatment
      largely abolished the ability of the CTB to bind to GM1, producing a fluorescence
      pattern similar to that reported for the human. The most abundant seminal plasma
      protein, PDC-109, was not responsible for this loss. As demonstration that the
      seminal plasma was not removing GM1, sperm exposed to seminal plasma were fixed
      before CTB addition, and again displayed fluorescence over the acrosome. These
      observations reconcile inconsistencies reported for the localization of GM1 in
      sperm of different species, and provide evidence for the segregation of GM1 to a
      stable subdomain in the plasma membrane overlying the acrosome.

PMID- 16452465
TI  - The chemokines, CX3CL1, CCL14, and CCL4, promote human trophoblast migration at
      the feto-maternal interface.
AB  - Human embryo implantation is a complex process involving blastocyst attachment to
      the endometrial epithelium and subsequent trophoblast invasion of the decidua.
      Chemokines, critical regulators of leukocyte migration, are abundant in
      endometrial epithelial and decidual cells at this time. We hypothesized that
      endometrial chemokines stimulate trophoblast invasion. Chemokine receptors CX3CR1
      and CCR1 were immunolocalized in human first-trimester implantation sites,
      specifically to endovascular extravillous trophoblasts, but not to the invading
      interstitial EVTs (iEVTs), with weak staining also on syncytium. CCR3 was
      localized to invading iEVTs and to microvilli on the syncytial surface.
      Expression of CX3CL1 (fractalkine), CCL7 (MCP-3), and their receptors (CX3CR1,
      CCR1, CCR2, CCR3, and CCR5) mRNA was examined in cellular components of the
      maternal-embryonic interface by RT-PCR. Both chemokines were abundant in entire
      endometrium and placenta, endometrial cells (primary cultures and HES, a human
      endometrial epithelial cell line) and trophoblast cell lines (JEG-3, ACIM-88, and
      ACIM-32). Chemokine receptor mRNA was expressed by placenta and trophoblast cell
      lines: CCR1 by all trophoblast cell types, whereas CCR2, CCR3, and CX3CR1 were
      more variable. CX3CR1, CCR1, CCR2, and CCR5 were also expressed by endometrial
      cells. Migration assays used the trophoblast cell line most closely resembling
      extravillous cytotrophoblast (AC1M-88). Trophoblast migration occurred in
      response to CX3CL1, CCL14, and CCL4, but not CCL7. Endometrial cell-conditioned
      media also stimulated trophoblast migration; this was attenuated by neutralizing
      antibodies to CX3CL1 and CCL4. Thus, chemokines are expressed by maternal and
      embryonic cells during implantation, whereas corresponding receptors are on
      trophoblast cells. Promotion of trophoblast migration by chemokines and
      endometrial cell conditioned medium indicates an important involvement of
      chemokines in maternal-fetal communication.

PMID- 16452467
TI  - Relationship between UDP-galactose 4'-epimerase activity and galactose
      sensitivity in yeast.
AB  - UDP-galactose 4'-epimerase (GALE) catalyzes the final step of the highly
      conserved Leloir pathway of galactose metabolism. Loss of GALE in humans results
      in a variant form of the metabolic disorder, galactosemia. Loss of GALE in yeast
      results in galactose-dependent growth arrest. Although the role of GALE in
      galactose metabolism has been recognized for decades, the precise relationship
      between GALE activity and galactose sensitivity has remained unclear. Here we
      have explored this relationship by asking the following. 1) Is GALE rate-limiting
      for galactose metabolism in yeast? 2) What is the relationship between GALE
      activity and galactose-dependent growth arrest in yeast? 3) What is the
      relationship between GALE activity and the abnormal accumulation of galactose
      metabolites in yeast? To answer these questions we engineered a strain of yeast
      in which GALE was doxycycline-repressible and studied these cells under
      conditions of intermediate GALE expression. Our results demonstrated a smooth
      linear relationship between galactose metabolism and GALE activity over a range
      from 0 to approximately 5% but a steep threshold relationship between growth rate
      in galactose and GALE activity over the same range. The relationship between
      abnormal accumulation of metabolites and GALE activity was also linear over the
      range from 0 to approximately 5%, suggesting that if the abnormal accumulation of
      metabolites underlies galactose-dependent growth-arrest in GALE-impaired yeast,
      either the impact of individual metabolites must be synergistic and/or the
      threshold of sensitivity must be very steep. Together these data reveal important
      points of similarity and contrast between the roles of GALE and galactose-1
      phosphate uridylyltransferase in galactose metabolism in yeast and provide a
      framework for future studies in mammalian systems.

PMID- 16452468
TI  - Regulation of intracellular glucose and polyol pathway by thiamine and
      benfotiamine in vascular cells cultured in high glucose.
AB  - Hyperglycemia is a causal factor in the development of the vascular complications
      of diabetes. One of the biochemical mechanisms activated by excess glucose is the
      polyol pathway, the key enzyme of which, aldose reductase, transforms d-glucose
      into d-sorbitol, leading to imbalances of intracellular homeostasis. We aimed at
      verifying the effects of thiamine and benfotiamine on the polyol pathway,
      transketolase activity, and intracellular glucose in endothelial cells and
      pericytes under high ambient glucose. Human umbilical vein endothelial cells and
      bovine retinal pericytes were cultured in normal (5.6 mmol/liter) or high (28
      mmol/liter) glucose, with or without thiamine or benfotiamine 50 or 100
      mumol/liter. Transketolase and aldose reductase mRNA expression was determined by
      reverse transcription-PCR, and their activity was measured
      spectrophotometrically; sorbitol concentrations were quantified by gas
      chromatography-mass spectrometry and intracellular glucose concentrations by
      fluorescent enzyme-linked immunosorbent assay method. Thiamine and benfotiamine
      reduce aldose reductase mRNA expression, activity, sorbitol concentrations, and
      intracellular glucose while increasing the expression and activity of
      transketolase, for which it is a coenzyme, in human endothelial cells and bovine
      retinal pericytes cultured in high glucose. Thiamine and benfotiamine correct
      polyol pathway activation induced by high glucose in vascular cells. Activation
      of transketolase may shift excess glycolytic metabolites into the pentose
      phosphate cycle, accelerate the glycolytic flux, and reduce intracellular free
      glucose, thereby preventing its conversion to sorbitol. This effect on the polyol
      pathway, together with other beneficial effects reported for thiamine in high
      glucose, could justify testing thiamine as a potential approach to the prevention
      and/or treatment of diabetic complications.

PMID- 16452469
TI  - Extracellular signal-regulated kinase-dependent proliferation is mediated through
      the protein kinase A/B-Raf pathway in human uveal melanoma cells.
AB  - Mutated B-Raf-mediated constitutive activation of ERK1/2 is involved in about 66%
      of cutaneous melanoma. By contrast, activating mutations in B-RAF are rare in
      ocular melanoma. This study aimed to determine the role of wild-type B-Raf ((WT)B
      Raf) in uveal melanoma cell growth. We used cell lines derived from primary
      tumors of uveal melanoma to assess the role of (WT)B-Raf in cell proliferation
      and to characterize its upstream regulators and downstream effectors. Melanoma
      cell lines expressing (WT)B-Raf and (WT)Ras grew with similar proliferation
      rates, showed constitutive activation of ERK1/2, and had similar levels of B-Raf
      expression and B-Raf kinase activity as melanoma cell lines expressing the
      activating V600E mutation ((V600E)B-Raf). They were equally as sensitive to
      pharmacological inhibition of MEK1/2 for cell proliferation and transformation as
      (V600E)B-Raf cells. siRNA-mediated depletion of Raf-1 did not affect either
      ERK1/2 activation, whereas siRNA-mediated depletion of B-Raf reduced cell
      proliferation by up to 65% through the inhibition of ERK1/2 activation,
      irrespective of the mutational status of B-Raf. Pharmacological inhibition of
      cAMP-dependent protein kinase (PKA) and siRNA-mediated depletion of PKA greatly
      reduced B-Raf activity, ERK1/2 activation, and cell proliferation in (WT)B-Raf
      cells, whereas it did not affect (V600E)B-Raf cells, demonstrating a key role of
      PKA in mediating (WT)B-Raf/ERK signaling for uveal melanoma cell growth.
      Moreover, inactivation or depletion of PKA did not affect Rap-1 activity, and Rap
      1 depletion did not affect either B-Raf activity or ERK1/2 activation. This ruled
      out a role for Rap1 in the PKA-mediated B-Raf/ERK activation in (WT)B-Raf cells.
      Finally, we demonstrated the importance of cyclin D1 in mediating PKA/(WT)B-Raf
      signaling for cell proliferation. Altogether, our results suggest that the PKA/B
      Raf pathway is a potential target for therapeutic strategies against (WT)B-Raf
      expressing uveal melanoma.

PMID- 16452470
TI  - Prolonged activation of cAMP-response element-binding protein and ATF-2 needed
      for nicotine-triggered elevation of tyrosine hydroxylase gene transcription in
      PC12 cells.
AB  - Phosphorylation (P-) of cAMP-response element-binding protein (CREB) by protein
      kinase A or mitogen-activated protein kinases was implicated in mediating the
      increased tyrosine hydroxylase (TH) gene expression after prolonged exposure to
      nicotine in vivo and in cell culture. We examined the time course and signaling
      pathways for phosphorylation of CREB and possible involvement of ATF-2. Treatment
      of PC12 cells with 200 microm nicotine triggered rapid but transient elevation of
      P-CREB followed by a second sustained rise after 2-5 h of continuous nicotine. In
      contrast, ERK1/2 was only phosphorylated with short term nicotine exposure. MEK
      inhibitor U0126 abolished nicotine-induced rise in P-ERK1/2, but not P-CREB, nor
      did it inhibit nicotine-evoked elevation in TH promoter activity, indicating that
      ERK1/2 was not needed for induction of TH gene expression by nicotine. In
      contrast, protein kinase A inhibitor H-89 or Ca(2+)/calmodulin-activated protein
      kinase inhibitor KN-93 reduced the nicotine-triggered rise in P-CREB and TH
      promoter activity. There was a delayed elevation of P-ATF-2 after 1 h of nicotine
      treatment, accompanied by increased ATF-2 protein. Upstream kinase JNK, but not
      p38, was phosphorylated especially after 5 min to 2 h of nicotine exposure. To
      examine the requirement for CREB and ATF-2, cells were transfected with dominant
      negative forms of ATF-2 or CREB. Both reduced the basal TH promoter activity and
      the response to nicotine. Knockdown of ATF-2 or CREB with siRNA did not alter
      basal TH promoter activity or mRNA but greatly attenuated the response to
      nicotine. The results suggest that both ATF-2 and CREB mediate activation of TH
      gene transcription by nicotine.

PMID- 16452471
TI  - Chromophore attachment to phycobiliprotein beta-subunits:
      phycocyanobilin:cysteine-beta84 phycobiliprotein lyase activity of CpeS-like
      protein from Anabaena Sp. PCC7120.
AB  - The gene alr0617, from the cyanobacterium Anabaena sp. PCC7120, which is
      homologous to cpeS from Gloeobacter violaceus PCC 7421, Fremyella diplosiphon
      (Calothrix PCC7601), and Synechococcus sp. WH8102, and to cpcS from Synechococcus
      sp. PCC7002, was overexpressed in Escherichia coli. CpeS acts as a
      phycocyanobilin: Cys-beta84-phycobiliprotein lyase that can attach, in vitro and
      in vivo, phycocyanobilin (PCB) to cysteine-beta84 of the apo-beta-subunits of C
      phycocyanin (CpcB) and phycoerythrocyanin (PecB). We found the following: (a) In
      vitro, CpeS attaches PCB to native CpcB and PecB, and to their C155I-mutants, but
      not to the C84S mutants. Under optimal conditions (150 mm NaCl and 500 mm
      potassium phosphate, 37 degrees C, and pH 7.5), no cofactors are required, and
      the lyase had a Km(PCB) = 2.7 and 2.3 microm, and a kcat = 1.7 x 10(-5) and 1.1 x
      10(-5) s(-1) for PCB attachment to CpcB (C155I) and PecB (C155I), respectively;
      (b) Reconstitution products had absorption maxima at 619 and 602 nm and
      fluorescence emission maxima at 643 and 629 nm, respectively; and (c) PCB
      CpcB(C155I) and PCB-PecB(C155I), with the same absorption and fluorescence
      maxima, were also biosynthesized heterologously in vivo, when cpeS was introduced
      into E. coli with cpcB(C155I) or pecB(C155I), respectively, together with genes
      ho1 (encoding heme oxygenase) and pcyA (encoding PCB:ferredoxin oxidoreductase),
      thereby further proving the lyase function of CpeS.

PMID- 16452472
TI  - Functional genomic analysis of CAF-1 mutants in Arabidopsis thaliana.
AB  - Duplication of chromatin following DNA replication requires spatial
      reorganization of chromatin domains assisted by chromatin assembly factor CAF-1.
      Here, we tested the genomic consequences of CAF-1 loss and the function of
      chromatin assembly factor CAF-1 in heterochromatin formation. Genes located in
      heterochromatic regions are usually silent, and we found that this
      transcriptional repression persists in the absence of CAF-1 in Arabidopsis.
      However, using microarrays we observed that genes that are active during late S
      phase, when heterochromatin is duplicated, were up-regulated in CAF-1 mutants.
      Arabidopsis CAF-1 mutants also have reduced cytological heterochromatin content;
      however, DNA methylation of pericentromeric repeats was normal, demonstrating
      that CAF-1 is not required for maintenance of DNA methylation. Instead,
      hypomethylation of the genome, which has only mild effects on the development of
      wild-type plants, completely arrested development of CAF-1 mutants. These results
      suggest that CAF-1 functions in heterochromatin formation. CAF-1 and DNA
      methylation, which is also needed for heterochromatin formation, have partially
      redundant functions that are essential for cell proliferation. Interestingly,
      transcriptional repression and heterochromatin compaction can be genetically
      separated, and CAF-1 is required only for the complete compaction of
      heterochromatin but not to maintain transcriptional repression of heterochromatic
      genes.

PMID- 16452473
TI  - Structural model for the mannose receptor family uncovered by electron microscopy
      of Endo180 and the mannose receptor.
AB  - The mannose receptor family comprises four members in mammals, Endo180 (CD280),
      DEC-205 (CD205), phospholipase A(2) receptor (PLA(2)R) and the mannose receptor
      (MR, CD206), whose extracellular portion contains a similar domain arrangement:
      an N-terminal cysteine-rich domain (CysR) followed by a single fibronectin type
      II domain (FNII) and 8-10 C-type lectin-like domains (CTLDs). These proteins
      mediate diverse functions ranging from extracellular matrix turnover through
      collagen uptake to homeostasis and immunity based on sugar recognition. Endo180
      and the MR are multivalent transmembrane receptors capable of interacting with
      multiple ligands; in both receptors FNII recognizes collagens, and a single CTLD
      retains lectin activity (CTLD2 in Endo180 and CTLD4 in MR). It is expected that
      the overall conformation of these multivalent molecules would deeply influence
      their function as the availability of their binding sites could be altered under
      different conditions. However, conflicting reports have been published on the
      three-dimensional arrangement of these receptors. Here, we have used single
      particle electron microscopy to elucidate the three-dimensional organization of
      the MR and Endo180. Strikingly, we have found that both receptors display
      distinct three-dimensional structures, which are, however, conceptually very
      similar: a bent and compact conformation built upon interactions of the CysR
      domain and the lone functional CTLD. Biochemical and electron microscopy
      experiments indicate that, under a low pH mimicking the endosomal environment,
      both MR and Endo180 experience large conformational changes. We propose a
      structural model for the mannose receptor family where at least two conformations
      exist that may serve to regulate differences in ligand selectivity.

PMID- 16452474
TI  - Src-dependent aprotein kinase C iota/lambda (aPKCiota/lambda) tyrosine
      phosphorylation is required for aPKCiota/lambda association with Rab2 and
      glyceraldehyde-3-phosphate dehydrogenase on pre-golgi intermediates.
AB  - The small GTPase Rab2 is required for membrane transport between the endoplasmic
      reticulum (ER) and the Golgi complex. Rab2 associates with pre-Golgi
      intermediates (also termed vesicular tubular clusters; VTCs) that sort cargo to
      the anterograde pathway from recycling proteins retrieved to the ER. Our previous
      studies have shown that Rab2 stimulates atypical protein kinase C iota/lambda
      (aPKCiota/lambda) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      recruitment to VTCs. Both aPKCiota/lambda and GAPDH bind directly to Rab2 and
      aPKCiota/lambda and GAPDH interact. Based on the reports demonstrating aPKCiota
      Src interaction and Src activity in the retrograde pathway (Golgi-ER), studies
      were initiated to learn whether Rab2 also promoted Src recruitment to VTCs. Using
      a quantitative membrane binding assay, we found that Rab2-stimulated Src membrane
      association in a dose-dependent manner. The recruited Src binds to
      aPKCiota/lambda and GAPDH on the membrane; however, Src does not interact with
      Rab2. The membrane-associated Src tyrosine phosphorylates aPKCiota/lambda on the
      VTC. To determine the consequence of aPKCiota/lambda tyrosine phosphorylation,
      the membrane binding assay was supplemented with the Src-specific tyrosine kinase
      inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine (PP2).
      Although Rab2, Src, and GAPDH recruitment was not affected, the Rab2-PP2-treated
      membranes contained a negligible amount of aPKCiota/lambda. Since Rab2 requires
      aPKCiota/lambda for the downstream recruitment of beta-coat protein (beta-COP) to
      VTCs, the Rab2-PP2-treated membranes were evaluated for the presence of beta-COP.
      Like aPKCiota/lambda, the membranes contained a negligible amount of beta-COP
      that was reflected by the drastic reduction in Rab2-dependent vesicle formation.
      These data suggest that Src-mediated tyrosine phosphorylation of aPKCiota/lambda
      facilitates aPKCiota/lambda association with Rab2-Src-GAPDH on VTCs, which is
      ultimately necessary for the downstream recruitment of beta-COP and release of
      Rab2-mediated retrograde-directed vesicles.

PMID- 16452476
TI  - Unveiling a hidden folding intermediate in c-type cytochromes by protein
      engineering.
AB  - Several investigators have highlighted a correlation between the basic features
      of the folding process of a protein and its topology, which dictates the folding
      pathway. Within this conceptual framework we proposed that different members of
      the cytochrome c (cyt c) family share the same folding mechanism, involving a
      consensus partially structured state. Pseudomonas aeruginosa cyt c(551) (Pa cyt
      c(551)) folds via an apparent two-state mechanism through a high energy
      intermediate. Here we present kinetic evidence demonstrating that it is possible
      to switch its folding mechanism from two to three state, stabilizing the high
      energy intermediate by rational mutagenesis. Characterization of the folding
      kinetics of one single-site mutant of the Pa cyt c(551) (Phe(7) to Ala) indeed
      reveals an additional refolding phase and a fast unfolding process which are
      explained by the accumulation of a partially folded species. Further kinetic
      analysis highlights the presence of two parallel processes both leading to the
      native state, suggesting that the above mentioned species is a non obligatory on
      pathway intermediate. Determination of the crystallographic structure of F7A
      shows the presence of an extended internal cavity, which hosts three "bound"
      water molecules and a H-bond in the N-terminal helix, which is shorter than in
      the wild type protein. These two features allow us to propose a detailed
      structural interpretation for the stabilization of the native and especially the
      intermediate states induced by a single crucial mutation. These results show how
      protein engineering, x-ray crystallography and state-of-the-art kinetics concur
      to unveil a folding intermediate and the structural determinants of its
      stability.

PMID- 16452475
TI  - Tumor necrosis factor receptor (TNFR)-associated factor 5 is a critical
      intermediate of costimulatory signaling pathways triggered by glucocorticoid
      induced TNFR in T cells.
AB  - Tumor necrosis factor receptor (TNFR) family members such as glucocorticoid
      induced TNFR (GITR) control T cell activation, differentiation, and effector
      functions. Importantly, GITR functions as a pivotal regulator of physiologic and
      pathologic immune responses by abrogating the suppressive effects of T regulatory
      cells and costimulating T effector cells. However, the molecular mechanisms
      underlying GITR-triggered signal transduction pathways remain unclear.
      Interestingly, GITR-induced stimulation of TNFR-associated factor (TRAF) 5
      deficient T cells resulted in decreased activation of nuclear factor kappaB as
      well as the mitogen-activated protein kinases p38 and extracellular signal
      regulated protein kinase, whereas activation of c-Jun N-terminal kinase was less
      affected. Consistent with impaired signaling, costimulatory effects of GITR were
      diminished in TRAF5-/- T cells. In sum, our studies indicate that TRAF5 plays a
      crucial role in GITR-induced signaling pathways that augment T cell activation.

PMID- 16452477
TI  - Identification of a novel region of the cytoplasmic Dynein intermediate chain
      important for dimerization in the absence of the light chains.
AB  - Cytoplasmic dynein is the multisubunit protein complex responsible for many
      microtubule-based intracellular movements. Its cargo binding domain consists of
      dimers of five subunits: the intermediate chains, the light intermediate chains,
      and the Tctex1, Roadblock, and LC8 light chains. The intermediate chains have a
      key role in the dynein complex. They bind the three light chains and the heavy
      chains, which contain the motor domains, but little is known about how the two
      intermediate chains interact. There are six intermediate chain isoforms, and it
      has been hypothesized that different isoforms may regulate specific dynein
      functions. However, there are little data on the potential combinations of the
      intermediate chain isoforms in the dynein complexes. We used co
      immunoprecipitation analyses to demonstrate that all combinations of homo- and
      heterodimers of the six intermediate chains are possible. Therefore the formation
      of dynein complexes with different combinations of isoforms is not limited by
      interaction between the various intermediate chains. We further sought to
      identify the domain necessary for the dimerization of the intermediate chains.
      Analysis of a series of truncation and deletion mutants showed that a 61-amino
      acid region is necessary for dimerization of the intermediate chain. This region
      does not include the N-terminal coiled-coil, the C-terminal WD repeat domain, or
      the three different binding sites for the Tctex1, LC8, and Roadblock light
      chains. Analytical gel filtration and covalent cross-linking of purified
      recombinant polypeptides further demonstrated that the intermediate chains can
      dimerize in vitro in the absence of the light chains.

PMID- 16452478
TI  - The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by
      hypoxia through a HIF-1alpha-dependent mechanism.
AB  - The monocarboxylate transporter MCT4 mediates lactic acid efflux from most
      tissues that are dependent on glycolysis for their ATP production. Here we
      demonstrate that expression of MCT4 mRNA and protein was increased >3-fold by a
      48-h exposure to 1% O(2), whereas MCT1 expression was not increased. The effect
      was mimicked by CoCl(2) (50 microm), suggesting transcriptional regulation by
      hypoxia-inducible factor 1alpha (HIF-1alpha). The predicted promoters for human
      MCT1, MCT2, and MCT4 were cloned into the pGL3 vector and shown to be active
      (luciferase luminescence) under basal conditions. Only the MCT4 promoter was
      activated (>2-fold) by hypoxia. No response was found in cells lacking HIF
      1alpha. Four potential hypoxia-response elements were identified, but deletion
      analysis implicated only two in the hypoxia response. These were just upstream
      from the transcription start site and also found in the mouse MCT4 promoter.
      Mutation of site 2 totally abolished the hypoxic response, whereas mutation of
      site 1 only reduced the response. Gel-shift analysis demonstrated that nuclear
      extracts of hypoxic but not normoxic HeLa cells contained two transcription
      factors that bound to DNA probes containing these hypoxia-response elements. The
      major shifted band was abolished by mutation of site 2, and supershift analysis
      confirmed that HIF-1alpha bound to this site. Binding of the second factor was
      abolished by mutation of site 1. We conclude that MCT4, like other glycolytic
      enzymes, is up-regulated by hypoxia through a HIF-1alpha-mediated mechanism. This
      adaptive response allows the increased lactic acid produced during hypoxia to be
      rapidly lost from the cell.

PMID- 16452479
TI  - NFkappaB signaling is induced by the oncoprotein Tio through direct interaction
      with TRAF6.
AB  - The transcription factor NFkappaB is a major regulator of genes involved in
      inflammation and oncogenesis. NFkappaB is induced upon stimulation of cellular
      receptors coupled to different intracellular signaling molecules. Further
      downstream, TRAF6 links at least two receptor pathways to take control of
      IkappaB, the administrator of NFkappaB activity. Here we report on a strong
      NFkappaB activation by Tio, a unique herpesviral oncoprotein promoting
      transformation of human T cells in a Src-kinase-dependent manner. NFkappaB
      induction by Tio is independent of Src-kinase interaction and tyrosine
      phosphorylation of Tio. Mutation of a glutamic acid-rich motif at the N terminus
      of Tio, corresponding to a TRAF6 consensus binding motif, completely abrogated
      NFkappaB activation. Cotransfection of a dominant negative TRAF6 construct led to
      a decrease in NFkappaB activation. Furthermore, we provide evidence that TRAF6
      directly binds to the Tio oncoprotein. Identification of TRAF6 as the direct
      target of Tio describes a novel mechanism for the constitutive activation of
      NFkappaB through an oncoprotein.

PMID- 16452480
TI  - Chronic ethanol intake impairs insulin signaling in rats by disrupting Akt
      association with the cell membrane. Role of TRB3 in inhibition of Akt/protein
      kinase B activation.
AB  - Chronic and excessive alcohol consumption is an important and modifiable risk
      factor for type 2 diabetes. We previously reported elevations in hepatic Class 1
      alcohol dehydrogenase (ADH) expression in ethanol-fed rats correspondent with
      reduced levels of mature, nuclear sterol-regulatory element-binding protein-1
      (SREBP-1), an insulin-induced transcriptional repressor of the ADH gene. In this
      report, we have studied the effects of insulin and ethanol on ADH gene expression
      in a highly differentiated rat hepatoma cell line (FGC-4), as well as the in vivo
      effects of chronic intake of an ethanol-containing diet on hepatic insulin
      signaling. Insulin inhibited ADH gene expression, and this was abolished by
      LY294002 (a phosphatidylinositol 3-kinase inhibitor) and small interfering RNA
      knockdown of SREBP-1. Chronic ethanol intake led to decreased phosphorylation of
      Akt (protein kinase B) at Thr308, increased phosphorylation of Akt at Ser473, and
      decreased phosphorylation of glycogen synthase kinase-3beta (a downstream
      effector of Akt). Hepatic membrane-associated Akt content was decreased and
      cytosolic Akt content was increased in rats fed an ethanol-containing diet. Thus,
      disruptive effects of ethanol on insulin signaling occurred via impaired
      phosphorylation of Akt at Thr308. TRB3, a negative regulator of Akt, was induced
      in liver of ethanol-fed rats. In ethanol-treated FGC-4 cells, small interfering
      RNA knockdown of TRB3 increased membrane-associated Akt and the phosphorylation
      of Akt at Thr308. Our results suggest that ethanol induces TRB3, which, through
      binding to the pleckstrin homology domain of Akt, prevents its plasma membrane
      association, Akt-Thr308 phosphorylation, and subsequent Akt-mediated signaling.
      Ethanol inhibition of insulin signaling reduces nuclear SREBP accumulation and
      results in disinhibition of Class 1 ADH transcription.

PMID- 16452481
TI  - Clotrimazole inhibits the Ca2+-ATPase (SERCA) by interfering with Ca2+ binding
      and favoring the E2 conformation.
AB  - Clotrimazole (CLT) is an antimycotic imidazole derivative that is known to
      inhibit cytochrome P-450, ergosterol biosynthesis and proliferation of cells in
      culture, and to interfere with cellular Ca(2+) homeostasis. We found that CLT
      inhibits the Ca(2+)-ATPase of rabbit fast-twitch skeletal muscle (SERCA1), and we
      characterized in detail the effect of CLT on this calcium transport ATPase. We
      used biochemical methods for characterization of the ATPase and its partial
      reactions, and we also performed measurements of charge movements following
      adsorption of sarcoplasmic reticulum vesicles containing the ATPase onto a gold
      supported biomimetic membrane. CLT inhibits Ca(2+)-ATPase and Ca(2+) transport
      with a K(I) of 35 mum. Ca(2+) binding in the absence of ATP and phosphoenzyme
      formation by the utilization of ATP in the presence of Ca(2+) are also inhibited
      within the same CLT concentration range. On the other hand, phosphoenzyme
      formation by utilization of P(i) in the absence of Ca(2+) is only minimally
      inhibited. It is concluded that CLT inhibits primarily Ca(2+) binding and,
      consequently, the Ca(2+)-dependent reactions of the SERCA cycle. It is suggested
      that CLT resides within the membrane-bound region of the transport ATPase,
      thereby interfering with binding and the conformational effects of the activating
      cation.

PMID- 16452482
TI  - ATM activation by ionizing radiation requires BRCA1-associated BAAT1.
AB  - ATM (ataxia telangiectasia mutated) is required for the early response to DNA
      damaging agents such as ionizing radiation (IR) that induce DNA double-strand
      breaks. Cells deficient in ATM are extremely sensitive to IR. It has been shown
      that IR induces immediate phosphorylation of ATM at Ser(1981), leading to
      catalytic activation of the protein. We recently isolated a novel BRCA1
      associated protein, BAAT1 (BRCA1-associated protein required for ATM activation
      1), by yeast two-hybrid screening and found that BAAT1 also binds to ATM,
      localizes to double-strand breaks, and is required for Ser(1981) phosphorylation
      of ATM. Small interfering RNA-mediated stable or transient reduction of BAAT1
      resulted in decreased phosphorylation of both ATM at Ser(1981) and CHK2 at
      Thr(68). Treatment of BAAT1-depleted cells with okadaic acid greatly restored
      phosphorylation of ATM at Ser(1981), suggesting that BAAT1 is involved in the
      regulation of ATM phosphatase. Protein phosphatase 2A-mediated dephosphorylation
      of ATM was partially blocked by purified BAAT1 in vitro. Significantly, acute
      loss of BAAT1 resulted in increased p53, leading to apoptosis. These results
      demonstrate that DNA damage-induced ATM activation requires a coordinated
      assembly of BRCA1, BAAT1, and ATM.

PMID- 16452483
TI  - The actin-depolymerizing factor homology and charged/helical domains of drebrin
      and mAbp1 direct membrane binding and localization via distinct interactions with
      actin.
AB  - Cytoskeletal dynamics are important for efficient function of the secretory
      pathway. ADP-ribosylation factor, ARF1, triggers vesicle coat assembly and, in
      concert with Cdc42, regulates actin polymerization and molecular motor-based
      motility. Drebrin and mammalian Abp1 (mAbp1) are actin-binding proteins found
      previously to bind to Golgi membranes in an ARF1-dependent manner in vitro.
      Despite sharing homology through two shared actin binding domains, drebrin and
      mAbp1 have different subcellular localization and bind to distinct actin
      structures on the Golgi apparatus. We find that the actin-depolymerizing factor
      homology (ADFH) and charged/helical actin binding domains of drebrin and mAbp1
      are sufficient for regulated binding to Golgi membranes and subcellular
      localization. We have used mutant proteins and chimeras between mAbp1 and drebrin
      to identify motifs that direct targeting. We find that a linker region between
      the ADFH and charged/helical domains confers Golgi binding properties to mAbp1.
      mAbp1 binds to a specific actin pool through its ADFH/linker domain that is not
      bound by drebrin. Drebrin localization to the cell surface was found to involve
      motifs within the charged/helical domain. Our results indicate that targeting of
      these proteins is directed through multiple distinct interactions with the actin
      cytoskeleton. The mechanisms for selective recruitment of mAbp1 and drebrin to
      Golgi membranes indicate how actin-based structures are able to select specific
      actin-binding proteins and, thus, carry out multiple different functions within
      cells.

PMID- 16452484
TI  - Pyruvate formate-lyase and a novel route of eukaryotic ATP synthesis in
      Chlamydomonas mitochondria.
AB  - Pyruvate formate-lyase (PFL) catalyzes the non-oxidative conversion of pyruvate
      to formate and acetyl-CoA. PFL and its activating enzyme (PFL-AE) are common
      among strict anaerobic and microaerophilic prokaryotes but are very rare among
      eukaryotes. In a proteome survey of isolated Chlamydomonas reinhardtii
      mitochondria, we found several PFL-specific peptides leading to the
      identification of cDNAs for PFL and PFL-AE, establishing the existence of a PFL
      system in this photosynthetic algae. Anaerobiosis and darkness led to increased
      PFL transcripts but had little effect on protein levels, as determined with
      antiserum raised against C. reinhardtii PFL. Protein blots revealed the
      occurrence of PFL in both chloroplast and mitochondria purified from aerobically
      grown cells. Mass spectrometry sequencing of C. reinhardtii mitochondrial
      proteins, furthermore, identified peptides for phosphotransacetylase and acetate
      kinase. The phosphotransacetylase-acetate kinase pathway is a common route of ATP
      synthesis or acetate assimilation among prokaryotes but is novel among
      eukaryotes. In addition to PFL and pyruvate dehydrogenase, the algae also
      expresses pyruvate:ferredoxin oxidoreductase and bifunctional aldehyde/alcohol
      dehydrogenase. Among eukaryotes, the oxygen producer C. reinhardtii has the
      broadest repertoire of pyruvate-, ethanol-, and acetate-metabolizing enzymes
      described to date, many of which were previously viewed as specific to anaerobic
      eukaryotic lineages.

PMID- 16452485
TI  - Suppression of apoptosis in the protein kinase Cdelta null mouse in vivo.
AB  - Protein kinase C (PKC) delta is an essential regulator of mitochondrial dependent
      apoptosis in epithelial cells. We have used the PKCdelta(-/-) mouse to ask if
      loss of PKCdelta protects salivary glands against gamma-irradiation-induced
      apoptosis in vivo and to explore the mechanism underlying protection from
      apoptosis. We show that gamma-irradiation in vivo results in a robust induction
      of apoptosis in the parotid glands of wild type mice, whereas apoptosis is
      suppressed by greater than 60% in the parotid glands of PKCdelta(-/-) mice.
      Primary parotid cells from PKCdelta(-/-) mice are defective in mitochondrial
      dependent apoptosis as indicated by suppression of etoposide-induced cytochrome c
      release, poly(ADP-ribose) polymerase cleavage, and caspase-3 activation. Notably,
      apoptotic responsiveness can be restored by re-introduction of PKCdelta by
      adenoviral transduction. Etoposide and gamma-irradiation-induced activation of
      p53 is similar in primary parotid cells and parotid glands from PKCdelta(+/+) and
      PKCdelta(-/-) mice, indicating that PKCdelta functions downstream of the DNA
      damage response. In contrast, activation of the c-Jun amino-terminal kinase is
      reduced in primary parotid cells from PKCdelta(-/-) cells and in parotid C5
      cells, which express a dominant inhibitory mutant of PKCdelta. Similarly, c-Jun
      amino-terminal kinase activation is suppressed in vivo in gamma-irradiated
      parotid glands from PKCdelta(-/-) mice. These studies indicate an essential role
      for PKCdelta downstream of the p53 response and upstream of the c-Jun amino
      terminal kinase activation in DNA damage-induced apoptosis in vivo and in vitro.

PMID- 16452486
TI  - Stress activation of mammary epithelial cell xanthine oxidoreductase is mediated
      by p38 MAPK and CCAAT/enhancer-binding protein-beta.
AB  - Xanthine oxidoreductase (XOR) catalyzes the formation of uric acid from xanthine
      and hypoxanthine and is recognized as a source of reactive oxygen and nitrogen
      species. Unexpectedly, XOR was found to play an essential role in milk secretion
      in the differentiating mammary gland, where it is an integral component of the
      milk fat globule. XOR gene expression in both mammary glands and differentiating
      mammary epithelial cells in culture is regulated by the lactogenic hormones
      prolactin and cortisol. Expression in mammary epithelial cells is also regulated
      by inflammatory cytokines and induced by cycloheximide. Cycloheximide was found
      to stimulate XOR gene expression in differentiating HC11 mouse mammary epithelial
      cells. Activation of XOR gene expression by both cycloheximide and inflammatory
      cytokines suggested that XOR may be regulated by stress-activated protein
      kinases, the MAPKs. We demonstrate here that XOR was induced in HC11 cells by low
      dose cycloheximide and that expression was blocked by inhibitors of p38 MAPK.
      Accumulation of phospho-p38 was stimulated by low dose cycloheximide. Low dose
      cycloheximide stress promoted phosphorylation and nuclear accumulation of the
      CCAAT/enhancer-binding protein-beta (C/EBPbeta) transcription factor, which was
      blocked by inhibition of p38. Furthermore, C/EBPbeta was found to activate the
      mouse XOR promoter, and XOR promoter-C/EBPbeta protein complexes were induced by
      low dose cycloheximide stress. These data demonstrate, for the first time, that
      mouse mammary epithelial cell XOR is regulated by p38 MAPK. They identify an
      essential function of the C/EBPbeta transcription factor in mouse XOR expression
      and suggest a potential role for p38 MAPK activation of C/EBPbeta in mammary
      epithelial cells.

PMID- 16452487
TI  - Dissection of the interaction of the human cytomegalovirus-derived US2 protein
      with major histocompatibility complex class I molecules: prominent role of a
      single arginine residue in human leukocyte antigen-A2.
AB  - Human cytomegalovirus encodes several proteins that interfere with expression of
      major histocompatibility complex (MHC) class I molecules on the surface of
      infected cells. The unique short protein 2 (US2) binds to many MHC class I
      allomorphs in the endoplasmic reticulum, preventing cell surface expression of
      the class I molecule in question. The molecular interactions underlying US2
      binding to MHC class I molecules and its allele specificity have not been fully
      clarified. In the present study, we first compared the sequences and the
      structures of US2 retained versus non-retained human leukocyte antigen (HLA)
      class I allomorphs to identify MHC residues of potential importance for US2
      binding. On the basis of this analysis, 18 individual HLA-A2 mutants were
      generated and the ability of full-length US2 to bind wild-type and mutated HLA-A2
      complexes was assessed. We demonstrate that Arg181 plays a critical role in US2
      mediated inhibition of HLA-A2 cell surface expression. The structural comparison
      of all known crystal structures of HLA-A2 either alone, or in complex with T cell
      receptor or the CD8 co-receptor, indicates that binding of US2 to HLA-A2 results
      in a unique, large conformational change of the side chain of Arg181. However,
      although the presence of Arg181 seems to be a prerequisite for US2 binding to HLA
      A2, it is not sufficient for binding to all MHC class I alleles.

PMID- 16452488
TI  - Agmatine stimulates hepatic fatty acid oxidation: a possible mechanism for up
      regulation of ureagenesis.
AB  - We demonstrated previously in a liver perfusion system that agmatine increases
      oxygen consumption as well as the synthesis of N-acetylglutamate and urea by an
      undefined mechanism. In this study our aim was to identify the mechanism(s) by
      which agmatine up-regulates ureagenesis. We hypothesized that increased oxygen
      consumption and N-acetylglutamate and urea synthesis are coupled to agmatine
      induced stimulation of mitochondrial fatty acid oxidation. We used 13C-labeled
      fatty acid as a tracer in either a liver perfusion system or isolated
      mitochondria to monitor fatty acid oxidation and the incorporation of 13C-labeled
      acetyl-CoA into ketone bodies, tricarboxylic acid cycle intermediates, amino
      acids, and N-acetylglutamate. With [U-13C16] palmitate in the perfusate, agmatine
      significantly increased the output of 13C-labeled beta-hydroxybutyrate,
      acetoacetate, and CO2, indicating stimulated fatty acid oxidation. The
      stimulation of [U-13C16]palmitate oxidation was accompanied by greater production
      of urea and a higher 13C enrichment in glutamate, N-acetylglutamate, and
      aspartate. These observations suggest that agmatine leads to increased
      incorporation and flux of 13C-labeled acetyl-CoA in the tricarboxylic acid cycle
      and to increased utilization of 13C-labeled acetyl-CoA for synthesis of N
      acetylglutamate. Experiments with isolated mitochondria and 13C-labeled octanoic
      acid also demonstrated that agmatine increased synthesis of 13C-labeled beta
      hydroxybutyrate, acetoacetate, and N-acetylglutamate. The current data document
      that agmatine stimulates mitochondrial beta-oxidation and suggest a coupling
      between the stimulation of hepatic beta-oxidation and up-regulation of
      ureagenesis. This action of agmatine may be mediated via a second messenger such
      as cAMP, and the effects on ureagenesis and fatty acid oxidation may occur
      simultaneously and/or independently.

PMID- 16452489
TI  - In vivo regulation of Grp78/BiP transcription in the embryonic heart: role of the
      endoplasmic reticulum stress response element and GATA-4.
AB  - The transcriptional activation of GRP78, which controls multiple signaling
      pathways of the unfolded protein response, has been used extensively as an
      indicator for the onset of endoplasmic reticulum stress in tissue culture
      systems. Here we investigate the mechanism of Grp78 induction during mouse
      embryonic development. Our results reveal that in transgenic mouse models,
      reporter gene activity driven by the Grp78 promoter is strongly activated during
      early embryonic heart development but subsides in later stages. This activation
      is strictly dependent on a 100-base pair region of the Grp78 promoter containing
      the endoplasmic reticulum stress response elements (ERSEs). Previous studies
      establish that endoplasmic reticulum stress induces in vivo binding of YY1 and
      the nuclear form of ATF6 to the ERSE. Since the expression of YY1 as well as ATF6
      is ubiquitous in the mouse embryo, activation of the Grp78 promoter in the early
      embryonic heart may involve a specific mechanism. Here we report that GATA-4, a
      transcription factor essential for heart development, binds to the Grp78 promoter
      in vivo and activates the ERSE, which does not contain a consensus GATA binding
      site. GATA-4 cooperatively activates the Grp78 promoter with YY1, and the DNA
      binding domain of YY1 is necessary and sufficient for this cooperation. In
      addition, GATA-4 activation of the Grp78 promoter is enhanced by the nuclear form
      of ATF6, and this synergy is further potentiated by YY1. These results suggest
      that during early heart organogenesis, Grp78 can be activated through cooperation
      between the cell type-specific transcription factors and ERSE-binding factors.

PMID- 16452490
TI  - World Kidney Day: an idea whose time has come.

PMID- 16452491
TI  - Explaining variability in mycophenolic acid exposure to optimize mycophenolate
      mofetil dosing: a population pharmacokinetic meta-analysis of mycophenolic acid
      in renal transplant recipients.
AB  - Large between- and within-patient variability has been observed in the
      pharmacokinetics of mycophenolic acid (MPA). However, conflicting results exist
      about the influence of patient characteristics that explain the variability in
      MPA exposure. This population pharmacokinetic meta-analysis of MPA in renal
      transplant recipients was performed to explore whether race, renal function,
      albumin level, delayed graft function, diabetes, and co-medication are
      determinants of total MPA exposure. A total of 13,346 MPA concentration-time data
      points from 468 renal transplant patients who participated in six clinical
      studies were combined and analyzed retrospectively. Sampling occasions ranged
      from day 1 after transplantation to 10 yr after transplantation. Concentration
      time data were analyzed with nonlinear mixed-effect modeling. Exposure to total
      MPA, as determined by MPA clearance, significantly increased with increasing
      renal function, albumin level, and hemoglobin as well as decreasing cyclosporine
      predose level (P<0.001). These variables could explain 18% of the between-patient
      and 38% of the within-patient variability in MPA exposure. Differences in MPA
      exposure between patients with or without delayed graft function or between
      patients of different races are likely to be caused by the effect of renal
      function on MPA exposure. Diabetes did not have an effect on MPA exposure. The
      clinical implication is that a change in renal function or albumin level provides
      an indication for therapeutic drug monitoring as MPA exposure may be altered.
      Patients in whom cyclosporine and mycophenolate mofetil are combined may need
      higher mycophenolate mofetil doses, especially during the early phase after
      transplantation than currently recommended for optimal MPA exposure.

PMID- 16452493
TI  - CD44 disruption prevents degeneration of the capillary network in obstructive
      nephropathy via reduction of TGF-beta1-induced apoptosis.
AB  - CD44 is a glycoprotein that is involved in inflammation and cell-cell/cell-matrix
      interactions, is upregulated in the kidney upon injury, and leads to fibrosis
      through enhancement of TGF-beta1 signaling. Absence of CD44 prevents development
      of renal fibrosis in unilateral ureteral obstruction (UUO). A hallmark of
      development of renal fibrosis is the degeneration of the capillary network. This
      study shows that CD44 is upregulated on capillary endothelial cells during UUO.
      For elucidation of the role of CD44 on peritubular endothelial cells in UUO,
      capillary network degeneration was compared in CD44+/+ and CD44-/- mice. As
      expected, degeneration of the capillary network was observed in CD44+/+ mice
      during UUO, associated with increased endothelial apoptosis. However, in the
      absence of CD44, degeneration of the network is prevented as a result of a
      decrease in the rate of apoptosis in endothelial cells. The divergence in
      endothelial apoptosis is not correlated to differential vascular endothelial
      growth factor or thrombospondin-1 expression. For further investigation of
      capillary regression, CD44+/+ and CD44-/- peritubular capillary endothelial cell
      lines were established. With the use of these cells, it is shown that interaction
      between CD44 and its ligand hyaluronic acid enhances the proapoptotic effect of
      TGF-beta1 but not thrombospondin-1 on endothelial cells, contributing to the
      degeneration of the capillary network. Blocking interaction between hyaluronic
      acid and CD44 therefore may be a potential therapeutic opportunity to preserve
      the capillary network and prevent the development of fibrosis in chronic renal
      disease.

PMID- 16452492
TI  - Mortality risk stratification in chronic kidney disease: one size for all ages?
AB  - Current National Kidney Foundation Kidney Disease Outcomes Quality Initiative
      staging criteria for chronic kidney disease (CKD) are intended to apply to all
      age groups. However, it is unclear whether different levels of estimated GFR
      (eGFR) have the same prognostic significance in older and younger patients. The
      study cohort was composed of Department of Veterans Affairs (VA) patients who
      were aged 18 to 100 yr and had at least one outpatient serum creatinine
      measurement between October 1, 2001, and September 30, 2002 (n=2583,911).
      Patients with ESRD were excluded. GFR was estimated using the Modification of
      Diet in Renal Disease equation using each patient's first outpatient creatinine
      measurement during the study period. The association of eGFR with survival was
      measured by age group. Twenty percent of cohort patients had an eGFR<60 ml/min
      per 1.73 m2, ranging from 3% among 18- to 44-yr-olds to as high as 49% among 85-
      to 100-yr-olds. Fifty-two percent (n=266,421) of cohort patients with an eGFR<60
      ml/min per 1.73 m2 had "very" moderate reductions in eGFR into the 50- to 59
      ml/min per 1.73 m2 range. The association of eGFR with mortality was weaker in
      the elderly than in younger age groups: Whereas severe reductions in eGFR were
      associated with an increased risk for death in all age groups, "very" moderate
      reductions in eGFR (50 to 59 ml/min per 1.73 m2) were associated with an
      increased adjusted risk for death only among patients who were younger than 65
      yr. Age-related attenuation of the association of eGFR with mortality was also
      present among women and black patients. In the clinical setting, mortality risk
      stratification in elderly patients should not be based on the same eGFR cut
      points as for younger age groups and would benefit from finer categorization of
      the 30- to 59-ml/min per 1.73 m2 eGFR group.

PMID- 16452494
TI  - Comparison of methods for determining renal function decline in early autosomal
      dominant polycystic kidney disease: the consortium of radiologic imaging studies
      of polycystic kidney disease cohort.
AB  - A decline in renal function suggests progression of chronic kidney disease. This
      can be determined by measured GFR (e.g., iothalamate clearance), serum creatinine
      (SCr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with
      autosomal dominant polycystic kidney disease and baseline creatinine clearance>70
      ml/min were followed annually for four visits. Iothalamate clearance, SCr, and
      creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was
      determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft
      Gault equations. Renal function slopes had a mean residual SD of 10.7% by
      iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation,
      and 14.8% by creatinine clearance. By each method, a decline in renal function
      (lowest quintile slope) was compared among baseline predictors. Hypertension was
      associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95%
      confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or
      OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.9]), and creatinine clearance (OR 2.0;
      95% CI 1.0 to 4.2). Each doubling of kidney volume at baseline was associated
      with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7
      [95% CI 1.1 to 2.6] or 2.1 [95% CI 1.4 to 3.3]), and creatinine clearance (OR
      1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR.
      Misclassification from changes in non-GFR factors (e.g., creatinine production,
      tubular secretion) conservatively biased associations with eGFR.
      Misclassification from method imprecision attenuated associations with creatinine
      clearance.

PMID- 16452495
TI  - Prevention of lithotripsy-induced renal injury by pretreating kidneys with low
      energy shock waves.
AB  - Lithotripsy shock waves (SW) to one renal pole damage that pole but protect the
      opposite pole from the damage inflicted by another, immediate application of SW.
      This study investigated whether the protection (1) occurs when the first
      treatment causes no injury, (2) is caused by SW or injury, (3) exhibits a
      threshold, and (4) occurs when the same pole receives both treatments. Six- to 7
      wk-old anesthetized female pigs were studied. The following groups were studied:
      group 1 (n=4), 2000 SW at 12 kV to one pole and 2000 SW at 24 kV (standard) to
      the opposite pole; group 2 (n=6), same as group 1 except 500 12-kV SW
      pretreatment; group 3 (n=8), 500 12-kV, 2000 standard SW, all to the same pole;
      and group 4 (n=8), same as group 3 except 100 12-kV SW pretreatment. Mean+/-SD
      lesion size in group 1, first pole treated, was 0.66+/-0.82% of functional renal
      volume (FRV; P<0.05 versus 5.22+/-3.6% FRV with no pretreatment [NP]; 95%
      confidence interval [CI] -7.0 to -2.1) and 0.50+/-0.68% FRV in the opposite pole
      after 2000 standard SW (P<0.05 versus NP; 95% CI -9.4 to -0.08). Mean lesion size
      (first pole) in group 2 was 0.020+/-0.028% FRV (P<0.01 versus NP; 95% CI -9.2 to 
      1.2) and 0.43+/-0.54% FRV in the opposite pole after 2000 standard SW (P<0.05
      versus NP; 95% CI -8.8 to -0.82). Same-pole SW (groups 3 and 4) also protected.
      Mean lesion sizes were 0.28+/-0.33% (P<0.01 versus NP; 95% CI -8.0 to -1.9) in
      group 3 and 0.39+/-0.48% FRV (P<0.01 versus NP; 95% CI -8.2 to -1.7) in group 4.
      It is concluded that the pretreatment protocol substantially limits the renal
      injury that normally is caused by SWL and occurs when the pretreatment and
      standard SW are applied to the same pole. The threshold for the protection may be
      <100 SW.

PMID- 16452496
TI  - Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of
      excessive Rho signaling.
AB  - Statins have been reported to confer renoprotection in several experimental
      models of renal disease through pleiotropic actions. The roles of statins in
      glomerular podocytes have not been explored. The objective of this study was to
      evaluate the effects of fluvastatin on podocyte and tubulointerstitial injury in
      puromycin aminonucleoside (PAN)-induced nephrosis. PAN induced massive
      proteinuria and serum creatinine elevation on day 7, which were significantly
      suppressed by fluvastatin. Immunofluorescence studies of podocyte-associated
      proteins nephrin and podocin revealed diminished and discontinuous staining
      patterns in rats with PAN nephrosis, indicating severe podocyte injury.
      Fluvastatin treatment dramatically mitigated the abnormal staining profiles.
      Reduction of nephrin expression by PAN and its reversal by fluvastatin were
      confirmed by quantitative analyses. By electron microscopy, effacement of foot
      processes was ameliorated in fluvastatin-treated rats. Fluvastatin also mitigated
      tubulointerstitial damage in PAN nephrosis, with the repression of PAN-induced NF
      kappaB and activator protein-1 activation in the kidneys. In addition, expression
      of activated membrane-bound small GTPase RhoA was markedly increased in the
      glomeruli of PAN nephrosis, which was inhibited by fluvastatin treatment. In
      cultured podocytes, fluvastatin suppressed PAN-evoked activation of RhoA and
      actin cytoskeletal reorganization. Furthermore, fasudil, a specific Rho-kinase
      inhibitor, successfully ameliorated PAN-induced podocyte damage and proteinuria.
      In summary, fluvastatin alleviated podocyte and tubulointerstitial injury in PAN
      nephrosis. The beneficial effects of fluvastatin on podocytes can be attributable
      to direct modulation of excessive RhoA activity. Our data suggest a therapeutic
      role for statins in clinical conditions that are relevant to podocyte injury.

PMID- 16452498
TI  - N-acetyl-seryl-aspartyl-lysyl-proline ameliorates the progression of renal
      dysfunction and fibrosis in WKY rats with established anti-glomerular basement
      membrane nephritis.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is hydrolyzed by
      angiotensin-converting enzyme, is a natural regulator of hematopoiesis. Here it
      is shown that Ac-SDKP inhibits TGF-beta action in mesangial cells. Because TGF
      beta is thought to play a pivotal role in the development and progression of
      glomerulonephritis, the therapeutic effects of Ac-SDKP on an established model of
      renal dysfunction and histologic alteration in Wistar-Kyoto rats with anti
      glomerular basement membrane nephritis was examined. Fourteen days after the
      induction of anti-glomerular basement membrane nephritis, the rats were treated
      subcutaneously with Ac-SDKP at a dose of 1 mg/kg per d for 4 wk. Treatment with
      Ac-SDKP significantly improved proteinuria and renal dysfunction, including
      increased plasma blood urea nitrogen and creatinine levels and decreased
      creatinine clearance. Histologic examination showed severe glomerulosclerosis and
      interstitial fibrosis in the vehicle-treated rats, whereas these histologic
      injuries were significantly ameliorated in rats that were treated with Ac-SDKP.
      The histologic improvements were accompanied by the suppression of gene and
      protein expression of fibronectin, interstitial collagen, and TGF-beta1 in the
      nephritic kidney. Furthermore, treatment with Ac-SDKP resulted in the inhibition
      of Smad2 phosphorylation, an increase in Smad7 expression in the kidney, and
      reduction of macrophage accumulation into the glomeruli and tubulointerstitium in
      nephritic rats. In conclusion, Ac-SDKP significantly ameliorated the progression
      of renal dysfunction and fibrosis even after the establishment of nephritis. The
      inhibitory effect of Ac-SDKP was mediated in part by the inhibition of TGF
      beta/Smad signal transduction and the inflammatory response. These findings
      suggest that Ac-SDKP treatment may be a novel and useful therapeutic strategy for
      the treatment of progressive renal diseases.

PMID- 16452497
TI  - Polycystin-1 induces resistance to apoptosis through the phosphatidylinositol 3
      kinase/Akt signaling pathway.
AB  - Polycystin-1 (PC-1), the PKD1 gene product, is a large receptor whose expression
      in renal epithelial cells results in resistance to apoptosis and tubulogenesis, a
      model consistent with the phenotype observed in patients. This study links PC-1
      expression to a signaling pathway that is known to be both antiapoptotic and
      important for normal tubulogenesis. This study found that PC-1 expression results
      in phosphorylation of Akt and downstream effectors and that phosphatidylinositol
      3-kinase (PI3-K) inhibitors prevent this process. In addition, it is shown that
      dominant negative Akt can revert PC-1-induced protection from apoptosis.
      Furthermore, it was observed that increased PI3-K beta activity in PC-1
      expressing MDCK cells seems to be dependent on both tyrosine-kinase activity and
      heterotrimeric G proteins. It also was found that PC-1-induced tubulogenesis is
      inhibited by PI3-K inhibitors. Taken together, these data suggest that the PI3
      K/Akt cascade may be a central modulator of PC-1 function and that its
      deregulation might be important in autosomal dominant polycystic kidney disease.

PMID- 16452499
TI  - CD40L proinflammatory and profibrotic effects on proximal tubular epithelial
      cells: role of NF-kappaB and lyn.
AB  - Chronic allograft nephropathy (CAN) is the main cause of renal graft loss, but
      its pathogenic mechanisms are still unclear. Immune system activation has been
      suggested as a key event in the development of CAN. CD40 is a co-stimulatory
      protein whose expression is upregulated in proximal tubular epithelial cells
      (PTEC) in acute rejection. This receptor interacts with CD40L, expressed by
      activated T cells. CD40L induces the production by PTEC of different
      proinflammatory cytokines, but very little is known of its profibrotic effects.
      The aim of this study was to investigate the effect of CD40/CD40L interaction on
      PTEC expression of plasminogen activator inhibitor-1 (PAI-1), a powerful
      profibrotic mediator, and monocyte chemoattractant protein-1 (MCP-1), a
      proinflammatory cytokine, and to investigate the signaling pathways that lead to
      these effects. Soluble CD40L induced a time-dependent increase in both PAI-1 and
      MCP-1 gene expression and protein production in PTEC. CD40 cross-linking on PTEC
      caused TNF-R-associated factors 2 and 6 membrane translocation. This event led to
      NF-kappaB activation, through the NF-kappaB-inducing kinase, and to a significant
      increase in the phosphorylation of lyn, a src-related tyrosine kinase. Lyn, upon
      phosphorylation, became strictly associated with caveolin-1, a scaffolding
      protein enriched in caveolae. Lyn inhibition did not have any effect on CD40L
      induced NF-kappaB activation and MCP-1 expression but abolished PAI-1 induction.
      On the contrary, NF-kappaB inhibition significantly reduced only MCP-1
      expression. In conclusion, CD40L could play a key role in the pathogenesis of CAN
      through PAI-1 induction. CD40L profibrotic and proinflammatory effects are
      mediated by different signaling pathways, suggesting that drugs that inhibit
      inflammation may not be equally effective in reducing fibrosis.

PMID- 16452500
TI  - Accumulation of immune complexes in glomerular disease is independent of locally
      synthesized c3.
AB  - Although complement activation can make immune complex glomerulonephritis worse,
      the third complement component also can solubilize immune complexes and thus
      reduce the severity of disease. How C3 that is produced within the kidney
      contributes to this balance is unknown. This study therefore investigated the
      relative roles of systemic and local C3 production in a model of glomerular
      immune complex disease. Injection of sheep anti-glomerular basement membrane
      antibody into preimmunized mice resulted in accumulation of immune complexes and
      progressive loss of function over 14 d that was much more marked in C3-deficient
      (C3-/-) mice. In C3-sufficient mice that received a transplant of a C3-/- mouse
      kidney and in C3-/- mice with C3-sufficient mouse kidney transplants, the
      severity and the pattern of injury went with the complement status of the
      recipient. That is, mice with deficient circulating C3 developed severe
      glomerular immune complex disease, whereas those with a high level of circulating
      C3 had well-preserved glomerular structure and function. It is concluded that
      circulating C3 is a critical factor in reducing the glomerular accumulation of
      immune complexes. Local synthesis of C3 did not have a major influence on this
      aspect of glomerular disease.

PMID- 16452501
TI  - Coordination and communication between the p53 and IGF-1-AKT-TOR signal
      transduction pathways.
AB  - Over the past 10 years the signal transduction networks for p53, IGF-1-AKT, and
      TOR pathways have been assembled in worms, flies, and mammals, and their
      functions elucidated. In the past 1-2 years a number of genes and their proteins
      have been identified that permit extensive communication and coordination between
      these pathways. These three pathways are involved in sensing and integrating
      signals arising from nutrient and growth factor availability, signals from
      sensory and sexual organs, and intrinsic and extrinsic stress signals. In turn
      these pathways regulate cell growth, proliferation, and death. These networks are
      central to our understanding of a variety of physiological and pathological
      conditions, including cancer, diabetes, and longevity.

PMID- 16452502
TI  - Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome
      remodeling complexes during an inflammatory response.
AB  - Studies of mammalian genes activated in response to an acute stimulus have
      suggested diverse mechanisms through which chromatin structure and nucleosome
      remodeling events contribute to inducible gene transcription. However, because of
      this diversity, the logical organization of the genome with respect to nucleosome
      remodeling and gene induction has remained obscure. Numerous proinflammatory
      genes are rapidly induced in macrophages in response to microbial infection.
      Here, we show that in lipopolysaccharide-stimulated macrophages, the catalytic
      BRG1/BRM subunits of the SWI/SNF class of ATP-dependent nucleosome remodeling
      complexes are consistently required for the activation of secondary response
      genes and primary response genes induced with delayed kinetics, but not for
      rapidly induced primary response genes. Surprisingly, a Mi-2beta complex was
      selectively recruited along with the SWI/SNF complexes to the control regions of
      secondary response and delayed primary response genes, with the Mi-2beta complex
      acting antagonistically to limit the induction of these gene classes. SWI/SNF and
      Mi-2beta complexes influenced cell size in a similarly antagonistic manner. These
      results provide insight into the differential contributions of nucleosome
      remodeling complexes to the rapid induction of defined classes of mammalian genes
      and reveal a robust anti-inflammatory function of Mi-2beta.

PMID- 16452503
TI  - A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C.
AB  - AP-1 (Activating Protein 1) transcription factor activity is tightly regulated at
      multiple levels, including dimer formation (i.e., Fos/Jun). Here we show that the
      intermediate filament protein lamin A/C suppresses AP-1 function through direct
      interaction with c-Fos, and that both proteins can interact and colocalize at the
      nuclear envelope (NE) in mammalian cells. Perinuclear localization of c-Fos is
      absent in Lmna-null cells but can be restored by lamin A overexpression. In
      vitro, preincubation of c-Fos with lamin A prior to the addition of c-Jun
      inhibits AP-1 DNA-binding activity. In vivo, overexpression of lamin A reduces
      the formation of c-Fos/c-Jun heterodimers, and suppresses AP-1 DNA-binding and
      transcriptional activity. Notably, c-Fos colocalizes with lamin A/C at the NE in
      starvation-synchronized quiescent cells lacking detectable AP-1 DNA binding. In
      contrast, serum-induced AP-1 DNA-binding activity coincides with abundant
      nucleoplasmic c-Fos expression without changes in lamin A/C localization. We also
      found that Lmna-null cells display enhanced proliferation. In contrast, lamin A
      overexpression causes growth arrest, and ectopic c-Fos partially overcomes lamin
      A/C-induced cell cycle alterations. We propose lamin A/C-mediated c-Fos
      sequestration at the NE as a novel mechanism of transcriptional and cell cycle
      control.

PMID- 16452504
TI  - Critical and distinct roles for key RET tyrosine docking sites in renal
      development.
AB  - Molecular mechanisms that lead to congenital anomalies of kidneys and the lower
      urinary tract (CAKUT) are poorly understood. To elucidate the molecular basis for
      signaling specificity of GDNF-mediated RET signaling in kidney development, we
      characterized mice that exclusively express either the human RET9 or RET51
      isoform, or express these isoforms with individual mutations in docking tyrosines
      for PTB and SH2-domain-containing adaptors Src (Y981), PLCgamma (Y1015), and Shc
      (Y1062). Our results provide evidence for differential and isoform-specific roles
      of these docking sites in murine kidney development. Homozygous Ret(RET9) and
      Ret(RET51) mice were viable and show normally developed kidneys, indicating
      redundant roles of human RET isoforms in murine kidney development. In the
      context of the RET51 isoform, only mutation of the docking Tyr 1015 (Y1015F)
      resulted in severe renal anomalies. These included bilateral megaureters and
      multicystic kidneys that were caused by supernumerary ureteric buds that fail to
      separate from the wolffian duct as well as decreased branching morphogenesis.
      Similar kidney and ureter defects were observed in RET9(Y1015F) mice that contain
      the Y1015F mutation in the RET9 isoform. Interestingly, loss of RET9(Y1062)
      mediated AKT/MAPK activation resulted in renal agenesis or kidney rudiments,
      whereas mutation of this residue in RET51 had no obvious effect on AKT/MAPK
      activity and renal development. These results reveal novel roles of key RET
      dependent signaling pathways in embryonic kidney development and provide murine
      models and new insights into the molecular basis for CAKUT.

PMID- 16452505
TI  - Control of ribonucleotide reductase localization through an anchoring mechanism
      involving Wtm1.
AB  - The control of deoxyribonucleotide levels is essential for DNA synthesis and
      repair. This control is exerted through regulation of ribonucleotide reductase
      (RNR). One mode of RNR regulation is differential localization of its subunits.
      In Saccharomyces cerevisiae, the catalytic subunit hererodimer, Rnr2/Rnr4, is
      localized to the nucleus while its regulatory subunit, Rnr1, is cytoplasmic.
      During S phase and in response to DNA damage, Rnr2-Rnr4 enters the cytoplasm,
      where it presumably combines with Rnr1 to form an active complex. The mechanism
      of its nuclear localization is not understood. Here, we report the isolation of
      the WTM (WD40-containing transcriptional modulator) proteins as regulators of
      Rnr2/Rnr4 localization. Overproduction of Wtm2 increased Rnr2/Rnr4. Deletion of
      WTM1, a homolog of WTM2, leads to the cytoplasmic localization of Rnr2/Rnr4, and
      increased hydroxyurea (HU)-resistance in mec1 mutants. Wtm1 binds Rnr2/4
      complexes and release them to the cytoplasm in response to DNA damage. Forced
      localization of Wtm1 to the nucleolus causes Rnr2/Rnr4 complexes to relocalize to
      the nucleolus. Thus, Wtm1 acts as a nuclear anchor to maintain nuclear
      localization of Rnr2/4 complexes outside of S phase. In the presence of DNA
      damage this association is disrupted and Rnr2/Rnr4 become cytoplasmic, where they
      join with Rnr1 to form an intact complex.

PMID- 16452506
TI  - Telomere elongation is under the control of the RNAi-based mechanism in the
      Drosophila germline.
AB  - Telomeres in Drosophila are maintained by transposition of specialized telomeric
      retroelements HeT-A, TAHRE, and TART instead of the short DNA repeats generated
      by telomerase in other eukaryotes. Here we implicate the RNA interference
      machinery in the control of Drosophila telomere length in ovaries. The abundance
      of telomeric retroelement transcripts is up-regulated owing to mutations in the
      spn-E and aub genes, encoding a putative RNA helicase and protein of the
      Argonaute family, respectively, which are related to the RNA interference (RNAi)
      machinery. These mutations cause an increase in the frequency of telomeric
      element retrotransposition to a broken chromosome end. spn-E mutations eliminate
      HeT-A and TART short RNAs in ovaries, suggesting an RNAi-based mechanism in the
      control of telomere maintenance in the Drosophila germline. Enhanced frequency of
      TART, but not HeT-A, attachments in individuals carrying one dose of mutant spn-E
      or aub alleles suggests that TART is a primary target of the RNAi machinery. At
      the same time, we detected enhanced HeT-A attachments to broken chromosome ends
      in oocytes from homozygous spn-E mutants. Double-stranded RNA (dsRNA)-mediated
      control of telomeric retroelement transposition may occur at premeiotic stages,
      resulting in the maintenance of appropriate telomere length in gamete precursors.

PMID- 16452507
TI  - Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction
      complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.
AB  - Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNA
      containing premature termination codons (PTCs). In mammalian cells, recognition
      of PTCs requires translation and depends on the presence on the mRNA with the
      splicing-dependent exon junction complex (EJC). While it is known that a key
      event in the triggering of NMD is phosphorylation of the trans-acting factor,
      Upf1, by SMG-1, the relationship between Upf1 phosphorylation and PTC recognition
      remains undetermined. Here we show that SMG-1 binds to the mRNA-associated
      components of the EJC, Upf2, Upf3b, eIF4A3, Magoh, and Y14. Further, we describe
      a novel complex that contains the NMD factors SMG-1 and Upf1, and the translation
      termination release factors eRF1 and eRF3 (SURF). Importantly, an association
      between SURF and the EJC is required for SMG-1-mediated Upf1 phosphorylation and
      NMD. Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association
      of SURF with EJC, which provides the link between the EJC and recognition of PTCs
      and triggers NMD.

PMID- 16452508
TI  - Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2
      mRNA 3' UTR: translational repression for dosage compensation.
AB  - MSL-2 (male-specific lethal 2) is the limiting component of the Drosophila dosage
      compensation complex (DCC) that specifically increases transcription from the
      male X chromosome. Ectopic expression of MSL-2 protein in females causes DCC
      assembly on both X chromosomes and lethality. Inhibition of MSL-2 synthesis
      requires the female-specific protein sex-lethal (SXL), which binds to the msl-2
      mRNA 5' and 3' untranslated regions (UTRs) and blocks translation through
      distinct UTR-specific mechanisms. Here, we purify translationally silenced msl-2
      mRNPs and identify UNR (upstream of N-ras) as a protein recruited to the 3' UTR
      by SXL. We demonstrate that SXL requires UNR as a corepressor for 3'-UTR-mediated
      regulation, imparting a female-specific function to the ubiquitously expressed
      UNR protein. Our results reveal a novel functional role for UNR as a
      translational repressor and indicate that UNR is a key component of a "fail-safe"
      dosage compensation regulatory system that prevents toxic MSL-2 synthesis in
      female cells.

PMID- 16452510
TI  - Rice GIBBERELLIN INSENSITIVE DWARF1 is a gibberellin receptor that illuminates
      and raises questions about GA signaling.

PMID- 16452513
TI  - First federal comparative effectiveness review examines GI disorder.

PMID- 16452511
TI  - Medical Reserve Corps pharmacists assist evacuees.

PMID- 16452509
TI  - Drosophila UNR is required for translational repression of male-specific lethal 2
      mRNA during regulation of X-chromosome dosage compensation.
AB  - The inhibition of male-specific lethal 2 (msl-2) mRNA translation by the RNA
      binding protein sex-lethal (SXL) is an essential regulatory step for X-chromosome
      dosage compensation in Drosophila melanogaster. The mammalian upstream of N-ras
      (UNR) protein has been implicated in the regulation of mRNA stability and
      internal ribosome entry site (IRES)-dependent mRNA translation. Here we have
      identified the Drosophila homolog of mammalian UNR as a cofactor required for SXL
      mediated repression of msl-2 translation. UNR interacts with SXL, a female
      specific protein. Although UNR is present in both male and female flies, binding
      of SXL to uridine-rich sequences in the 3' untranslated region (UTR) of msl-2
      mRNA recruits UNR to adjacent regulatory sequences, thereby conferring a sex
      specific function to UNR. These data identify a novel regulator of dosage
      compensation in Drosophila that acts coordinately with SXL in translational
      control.

PMID- 16452514
TI  - New drug and biologic product approvals, 2005.

PMID- 16452515
TI  - Backtracking: pursuing residency training after working.

PMID- 16452517
TI  - Effect of methylphenidate formulation on treatment patterns and use of emergency
      room services.
AB  - PURPOSE: The treatment patterns of and use of emergency room services by patients
      with attention-deficit/hyperactivity disorder (ADHD) who initiated therapy with
      thrice-daily, immediate-release (IR) methylphenidate versus once-daily, extended
      release (ER) oral system methylphenidate were studied. METHODS: Using a large
      claims database, patients who were newly initiated on either ER methylphenidate
      or IR methylphenidate were retrospectively identified. Analysis of covariance was
      used to examine differences in treatment patterns between individuals who
      initiated therapy on ER methylphenidate and those who initiated therapy on IR
      methylphenidate. Multivariate regressions were used to examine the probability of
      visiting the emergency room and the number of visits to the emergency room.
      RESULTS: Of the 5939 patients who met the inclusion criteria, 4785 were initiated
      on ER methylphenidate and 1154 were initiated on IR methylphenidate.
      Significantly fewer patients initiated on ER methylphenidate had a 15- or 30-day
      gap in therapy or switched to another ADHD medication (p < 0.0001 for all
      comparisons). In addition, patients initiated on the ER formulation had a
      significantly longer duration of therapy than did those who received IR
      methylphenidate (p < 0.0001). Patients who received initial treatment with ER
      methylphenidate were also significantly less likely to visit an emergency room
      (odds ratio, 0.79; p = 0.01) and had, on average, 0.21 fewer visit to the
      emergency room (p = 0.0101). CONCLUSION: A retrospective analysis of a patient
      database demonstrated that initial treatment with ER methylphenidate for patients
      with ADHD was associated with longer treatment periods, fewer switches in
      therapy, increased patient adherence, and a lower usage rate of emergency room
      services compared with initial treatment with IR methylphenidate.

PMID- 16452518
TI  - Children's acetaminophen exposures reported to a regional poison control center.
AB  - PURPOSE: The patient characteristics, doses taken, and types of exposures in
      children with acetaminophen-related exposures reported to a regional poison
      control center (RPCC) were studied. METHODS: A retrospective review was conducted
      of all acetaminophen exposures that occurred between October 31, 2000, and
      October 31, 2003, in children younger than 18 years who were managed by an RPCC.
      Children were grouped into three age categories: less than 6 years (group 1), 6
      12 years (group 2), and 13-17 years (group 3). Data collected included patient
      demographics, drug details, type of exposure, time since exposure, exposure site,
      and caller site. RESULTS: There were 473 exposures to acetaminophen: 76% in group
      1, 3% in group 2, and 21% in group 3. Sex was distributed equally among groups,
      except group 3 was 83% females. The majority of callers seeking information on
      acetaminophen ingestion in children younger than 12 years were family members
      (62%), whereas health professionals (61%) were the most common callers for
      children over 12 years. Unintentional ingestion was the most common type of
      exposure in group 1 (100%) and group 2 (93.7%). In group 3, intentional
      ingestions were more common (91%), with females representing far more of these
      exposures than males (87% versus 14%, respectively). Acetaminophen doses over 200
      mg/kg were ingested by 47% of children in group 3. CONCLUSION: Most acetaminophen
      exposures reported to an RPCC occurred in children less than six years of age and
      were unintentional, whereas exposures in children over 12 years were more likely
      to be intentional overdoses.

PMID- 16452519
TI  - ASHP national survey of pharmacy practice in hospital settings: dispensing and
      administration--2005.
AB  - PURPOSE: Results of the 2005 ASHP national survey of pharmacy practice in
      hospital settings that pertain to dispensing and administration are presented.
      METHODS: A stratified random sample of pharmacy directors at 1173 general and
      children's medical-surgical hospitals in the United States was surveyed by mail.
      RESULTS: The response rate was 43.5%. Most hospitals had a centralized drug
      distribution system; however, there is evidence of growth in decentralized models
      compared with data from 2002. Automated dispensing cabinets were used by 72% of
      hospitals and robots by 15%. The percentage of doses dispensed in unit dose form
      increased, as did the use of two-pharmacist checks for high-risk drugs and high
      risk patient groups. However, the percentage of medication preparation and
      dispensing quality-improvement programs declined over the past six years.
      Medication administration records (MARs) have become increasingly computerized
      over the past six years. Consequently, the use of handwritten MARs has declined
      substantially. Technology implemented at the administration step of the
      medication-use process is continuing to grow. Bar-code technology was implemented
      by 9.4% of hospitals, and 32.2% of hospitals had smart infusion pumps. Pharmacy
      hours of operation were stable, with 30% of hospitals providing around-the-clock
      services. About 12% of hospitals are using off-site medication order review and
      entry after hours. Pharmacy staffing has steadily increased over the past three
      years; however, hospital pharmacies reported a 5.6% vacancy rate. CONCLUSION:
      Safe systems continue to be in place in most hospitals, but the adoption of new
      technology is changing the philosophy of medication distribution. Pharmacists are
      continuing to improve medication use at the dispensing and administration steps
      of the medication-use process.

PMID- 16452520
TI  - Literacy and perceived barriers to medication taking among homeless mothers and
      their children.
AB  - PURPOSE: The relation of medical literacy to women-reported barriers to taking
      medication themselves or giving medication to their children was studied.
      METHODS: Women in 18 homeless shelters in four counties in central North Carolina
      were recruited. Head-of-household homeless mothers with psychiatric or substance
      abuse disorders and dependent children were eligible to participate. Trained
      interviewers administered a site-specific questionnaire on medication use.
      RESULTS: One hundred sixty-four homeless women participated. Forty-two percent of
      the women were currently taking a medication. Forty-six percent of the women
      stated that there was a barrier to taking their medications as prescribed.
      Medical literacy was not significantly related to whether women felt there were
      barriers to taking a medication. Seventy-five percent of the women reported
      having one or more children living with them. Thirty-seven percent reported
      having a child with asthma live with them, and 12% reported having a child with
      attention-deficit disorder. Forty percent reported a barrier to giving their
      child a needed medication. Taste was the most commonly reported barrier. Women
      with lower medical literacy and younger women were significantly more likely to
      report a barrier to giving their children a needed medication. Over 80% of women
      listed pharmacists as their first or second choice for receiving drug information
      orally. CONCLUSION: Race and perceived barriers to medication use affected the
      medication-taking behavior of homeless women, while their age and literacy level
      affected the reporting rates of the barriers to medication use for their
      children. Homeless women preferred receiving both written and oral drug
      information from a physician or a pharmacist.

PMID- 16452521
TI  - Potential benefits and problems with computerized prescriber order entry:
      analysis of a voluntary medication error-reporting database.
AB  - PURPOSE: The potential benefits and problems associated with computerized
      prescriber-order-entry (CPOE) systems were studied. METHODS: A national voluntary
      medication error-reporting database, Medmarx, was used to compare facilities that
      had CPOE with those that did not have CPOE. The characteristics of medication
      errors reportedly caused by CPOE were explored, and the text descriptions of
      these errors were qualitatively analyzed. RESULTS: Facilities with CPOE reported
      fewer inpatient medication errors and more outpatient medication errors than
      facilities without CPOE, but the statistical significance of these differences
      could not be determined. Facilities with CPOE less frequently reported medication
      errors that reached patients (p < 0.01) or harmed patients (p < 0.01). More than
      7000 CPOE-related medication errors were reported over seven months in 2003, and
      about 0.1% of them resulted in harm or adverse events. The most common CPOE
      errors were dosing errors (i.e., wrong dose, wrong dosage form, or extra dose).
      Both quantitative and qualitative analyses indicate that CPOE could lead to
      medication errors not only because of faulty computer interface, mis
      communication with other systems, and lack of adequate decision support but also
      because of common human errors such as knowledge deficit, distractions,
      inexperience, and typing errors. CONCLUSION: A national, voluntary medication
      error-reporting database cannot be used to determine the effectiveness of a CPOE
      system in reducing medication errors because of the variability in the number of
      reports from different institutions. However, it may provide valuable information
      on the specific types of errors related to CPOE systems.

PMID- 16452522
TI  - Predictors of rehospitalization after acute coronary syndromes.

PMID- 16452523
TI  - Effect on health outcomes of a community-based medication therapy management
      program for seniors with limited incomes.

PMID- 16452524
TI  - Amifostine-induced back pain: a case report.

PMID- 16452525
TI  - Role of peripheral innervation in p-chloroamphetamine-induced ejaculation in
      anesthetized rats.
AB  - The occurrence of ejaculation, which consists of 2 distinct phases (emission and
      expulsion), requires a tight coordination of peripheral autonomic and somatic
      nerves. However, some aspects of the mechanism of ejaculation are not clearly
      defined. To clarify this issue, we used the p-chloroamphetamine (PCA)-induced
      ejaculation model in anesthetized rats and investigated the effects of selective
      peripheral nerves lesions on seminal vesicle and bulbospongiosus (BS) muscle
      activities as representing physiological markers of emission and expulsion
      phases, respectively. In intact rats, ejaculation induced with PCA
      (intraperitoneal 5 mg/kg) correlated with coordinated increases in seminal
      vesicle pressure (SVP) and BS electromyographic activity. PCA-induced ejaculation
      was still observed in rats with bilateral lesion of hypogastric nerves (HNx),
      lumbar paravertebral sympathetic chain (LSCx), or dorsal nerves of the penis
      (DNPx). Conversely, bilateral section of pelvic nerves (PNx) or L6-S1 dorsal
      roots (DRx) abolished PCA-induced ejaculation. The amplitude of SVP increases
      induced by PCA was reduced in PNx, HNx, and LSCx rats, whereas it was unchanged
      in DRx and DNPx rats. The time interval between SVP increases and BS muscle
      contractions induced by PCA was comparable in the different neural lesion groups.
      In conclusion, PCA initiates both emission and expulsion independently from each
      other. In this model, afferents conveyed by the pelvic nerves appear to be
      unnecessary for occurrence of BS muscle contractions but are essential for a
      complete ejaculatory response.

PMID- 16452526
TI  - Expression of orphan receptors TR2, TR3, TR4, and p53 in heat-treated testis of
      cynomolgus monkeys (Macaca fascicularis).
AB  - To investigate the possible role of testicular orphan receptors (TR) TR2, TR3,
      and TR4 in the process of germ cell apoptosis in the heat-treated testis of
      monkey, we have examined the spatiotemporal expression of the 3 TR mRNAs in
      relation to p53 mRNA levels in the monkey testis by in situ hybridization and
      reverse transcription polymerase chain reaction techniques. The results showed
      that TR2 mRNA was confined to spermatocytes; TR4 and TR3 mRNAs were expressed in
      both spermatocytes and spermatids. The heat treatment did not change TR2 mRNA
      level but significantly reduced TR4 mRNA expression in spermatocytes on days 3
      and 8 after the heat treatment. TR3 mRNA expression was affected by the heat
      treatment in a time-dependent manner, with the lowest level on day 30 after the
      heat shock. Low to moderate signal for p53 mRNA was detected in spermatocytes
      before treatment, which increased dramatically on days 3, 8, and 30 after the
      heat shock. The coincident expression of the testicular TR3 and p53 mRNA,
      spatially and time dependently, implied that the decrease in TR3 expression in
      the heat-treated testis might be closely related to the p53 signal pathway,
      whereas the temporal decrease in TR4 production in the testis at the early stage
      indicated that this orphan receptor might be also involved in germ cell
      apoptosis. The data suggest that TR3, TR4, and p53 could be important regulators
      of germ cell apoptosis induced by the heat treatment, whereas TR2 might not be a
      key regulator in this process.

PMID- 16452527
TI  - The multi PDZ domain protein MUPP1 as a putative scaffolding protein for
      organizing signaling complexes in the acrosome of mammalian spermatozoa.
AB  - Spermatozoa undergo complex sequences of precisely timed events during the
      process of fertilization. These priming events, which comprise capacitation, egg
      recognition, acrosome reaction, and sperm-oocyte fusion, are regulated by the
      activation of different intracellular signaling pathways. The efficacy and
      accuracy of signal transduction pathways often depend on the assembly of
      multiprotein signaling complexes, thereby coordinating and guiding the flow of
      regulatory information. To address the question whether PDZ-domain proteins, the
      most abundant protein interaction modules involved in the assembly of
      supramolecular signaling complexes, are present in rodent sperm, homologue of the
      RT-PCR approaches were performed with specific primer pairs for the vertebrate
      INAD-like PDZ domain protein MUPP1. The results revealed that this scaffolding
      protein, which comprises 13 different PDZ domains, is expressed in mouse testis.
      To obtain further support for the expression of the multi-PDZ domain protein
      MUPP1 in testicular tissue, immunohistochemical as well as immunocytochemical
      experiments were performed using a MUPP1-specific antibody. Detailed analyses of
      the spatial MUPP1-expression profile revealed that immunoreactivity is
      concentrated within the acrosomal region of round as well as elongated mouse
      spermatozoa. These results were confirmed in experimental approaches
      demonstrating that MUPP1 immunofluorescence was shed off from the acrosome region
      after acrosome reaction. To examine whether MUPP1 is also present in other
      mammalian sperm, immunocytochemical approaches were performed with isolated
      bovine as well as human sperm. The results revealed prominent MUPP1 expression
      which was restricted to the apical acrosomal region and, most notably, to the
      equatorial segment of the acrosome. The predominant expression profile of MUPP1
      in sperm of different mammalian species suggests that this PDZ-domain protein may
      be involved in organizing signaling molecules mediating primary reactions of
      fertilization.

PMID- 16452528
TI  - Semen and sperm reference ranges for men 45 years of age and older.
AB  - The most widely used reference values for human semen and sperm variables were
      developed by the World Health Organization (WHO) to help assess the fertility
      status of men interested in reproduction (typically a younger population). In
      this retrospective analysis, data from a large population of men aged 45 years or
      older were analyzed to derive semen and sperm reference ranges for an older
      population. Baseline semen samples were obtained from 1174 men with no or mild
      erectile dysfunction (ED) during the screening phase of two clinical trials
      evaluating the effects of a drug on human spermatogenesis. The median values and
      95% reference ranges for 4 measured semen and sperm parameters (semen volume,
      sperm concentration, sperm motility, and sperm morphology) and 1 derived
      parameter (total sperm count) were calculated for the population and by age
      quartile. These references ranges were compared to established WHO reference
      values. Associations between the semen and sperm parameters and smoking status,
      alcohol use, and serum hormone concentrations were also analyzed. The mean age
      was 52.9 years (range: 45-80). Median semen volume, sperm motility, and sperm
      morphology parameters declined significantly with age. Only 46% of study subjects
      had baseline values for semen and sperm parameters that met or surpassed all the
      WHO reference values. This is the first study to statistically derive semen
      reference ranges from a large population of men aged 45 years or older. The
      observation that less than half the men in this study met all 4 WHO reference
      values for measured semen and sperm parameters underscores the need for age
      specific reference ranges.

PMID- 16452529
TI  - Cybernetic principles in the systematic concept of hypothalamic feeding control.
AB  - Research on biological mechanisms of eating behavior and related disorders, such
      as obesity and anorexia nervosa, has become a large field of research in the last
      15 years. With the discovery of peptides related to hypothalamic control of food
      intake (e.g. leptin and ghrelin) the search for the biological 'master key' of
      feeding control was renewed. As a result, mid-20th century biological concepts
      based on systematic and cybernetic thoughts fell into oblivion. This review
      highlights discoveries of hypothalamic-controlled feeding and eating behavior
      with a cybernetic and systematic perspective. Interestingly, older ideas of
      hypothalamic function offer possibilities for the incorporation of new molecular
      discoveries into systematic concepts of feeding behavior.

PMID- 16452530
TI  - Osteoporosis and male age-related hypogonadism: role of sex steroids on bone
      (patho)physiology.
AB  - Male age-related bone loss is caused, at least in part, by hypogonadism that
      occurs with advancing age. The study of the effects of sex steroids on bone
      physiology in men has recently highlighted the central role of estrogens on bone
      pathophysiology. This review focuses on particular aspects of bone physiology and
      pathophysiology in aging men, noting both the similarities to and the differences
      from female counterparts. In particular, the role of sex steroids on bone sexual
      dimorphism in health and disease has been analyzed.

PMID- 16452531
TI  - Quinagolide--a valuable treatment option for hyperprolactinaemia.
AB  - Hyperprolactinaemia is characterised by gonadal dysfunction, including
      infertility and reduced libido and, if left untreated, is associated with an
      increased risk of long-term complications, such as osteoporosis. The first-line
      therapy for patients with hyperprolactinaemia is pharmacological intervention
      with a dopamine agonist. Currently, there are three dopamine agonists available
      for hyperprolactinaemia therapy: bromocriptine, quinagolide and cabergoline.
      Bromocriptine has a long history of use; however, a range of 5-18% of patients
      are reported to show bromocriptine resistance, with only partial lowering of
      plasma prolactin levels and an absence of tumour shrinkage. The newer dopamine
      agonists, quinagolide and cabergoline, offer improved efficacy over
      bromocriptine, with a lower incidence of adverse events. Quinagolide and
      cabergoline have also demonstrated efficacy in many patients intolerant or
      resistant to bromocriptine. Thus, the selection of dopamine agonists available
      provides more than one option for pharmacological intervention of
      hyperprolactinaemia. This review discusses the clinical use of quinagolide in
      comparison to other dopamine agonists for hyperprolactinaemia therapy.
      Quinagolide may improve patient compliance to treatment owing to its reduced side
      effect profile, simple and rapid titration over just 7 days, once-daily dosing
      regimen and easy to use starter pack (available in some countries). Quinagolide
      offers an additional benefit for patients wishing to become pregnant, as it can
      be used until the point of confirmation of pregnancy. Therefore, as a well
      tolerated and effective therapy, with a simple dosing regimen, quinagolide should
      be considered as a first-line therapy in the treatment of hyperprolactinaemia.

PMID- 16452532
TI  - Vascular and renal function in experimental thyroid disorders.
AB  - This review focuses on the effects of thyroid hormones in vascular and renal
      systems. Special emphasis is given to the mechanisms by which thyroid hormones
      affect the regulation of body fluids, vascular resistance and, ultimately, blood
      pressure. Vascular function is markedly affected by thyroid hormones that produce
      changes in vascular reactivity and endothelial function in hyper- and
      hypothyroidism. The hypothyroid state is accompanied by a marked decrease in
      sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration
      that may play a role in the reduced blood pressure of hypothyroid rats, as well
      as in the preventive effects of hypothyroidism on experimental hypertension.
      Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors
      vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an
      increased endothelium-dependent responsiveness that may be secondary to the shear
      stress induced by the hyperdynamic circulation, and that may contribute to the
      reduced vascular resistance characteristic of this disease. Thyroid hormones also
      have important effects in the kidney, affecting renal growth, renal
      haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a
      resetting of the pressure-natriuresis relationship related to hyperactivity of
      the renin-angiotensin system, which contributes to the arterial hypertension
      associated with this endocrine disease. Moreover, thyroid hormones affect the
      development and/or maintenance of various forms of arterial hypertension. This
      review also describes recent advances in our understanding of thyroid hormone
      action on nitric oxide and oxidative stress in the regulation of cardiovascular
      and renal function and in the long-term control of blood pressure.

PMID- 16452533
TI  - Elevated transaminases during medical treatment of acromegaly: a review of the
      German pegvisomant surveillance experience and a report of a patient with
      histologically proven chronic mild active hepatitis.
AB  - OBJECTIVE: The new GH receptor antagonist pegvisomant is the most effective
      medical therapy to normalize IGF-I levels in patients with acromegaly. Based on
      currently available data pegvisomant is well tolerated; however, treatment
      induced elevation of transaminases has been reported and led to the necessity for
      drug discontinuation in some patients in the pivotal studies. The aim of this
      study was to evaluate and characterize the prevalence of elevated transaminases
      and to describe in detail the findings in a single case who required drug
      discontinuation because of elevation of transaminases which emerged during
      treatment and who underwent liver biopsy. DESIGN AND METHODS: Retrospective
      safety analyses were carried out on 142 patients with acromegaly receiving
      pegvisomant treatment in Germany between March 2003 and the end of 2004. Of these
      patients, 123 were documented in a post-marketing surveillance study, one case of
      elevated transaminases was reported spontaneously and the other patients were
      treated in a clinical study. RESULTS: Mean treatment duration with pegvisomant in
      the ongoing observational study at the end of 2004 was 28.3 +/- 19.9 (S.D.)
      weeks. Twelve out of the 142 patients had elevated transaminases above three
      times the upper limit of normal, likely caused by biliary obstruction in five of
      the patients. All patients but one affected by elevated transaminases had been
      previously treated with somatostatin analogues. In six out of 142 (4%) of
      patients, pegvisomant was permanently withdrawn because of elevated
      transaminases. The same number of patients showed a transient increase of
      transaminases with either spontaneous remission without dose modification (n = 4)
      or no re-increase of transaminases after temporary discontinuation and re
      exposure (n = 2). The liver biopsy of one patient who was permanently withdrawn
      showed a chronic mild hepatitis with a mixed portal inflammation including
      eosinophilic granulocytes. CONCLUSIONS: Liver function tests should be regularly
      followed on pegvisomant treatment. Biliary complications, which may arise from
      restitution of normal gall bladder motility after cessation of somatostatin
      analogue treatment, need to be differentiated from pegvisomant-induced
      abnormalities. The histological pattern of the liver biopsy performed in one of
      the patients showed a mild chronic active hepatitis. The lack of dose dependency
      and rather low frequency of elevated transaminases in those cases where a biliary
      disorder was excluded render this reaction an idiosyncratic drug toxicity.

PMID- 16452534
TI  - Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a
      familial case and management with an aromatase inhibitor.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder
      characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous
      pigmentation and increased predisposition to various neoplasms. Endocrine
      manifestations in PJS include gynecomastia due to calcified Sertoli cell
      testicular tumors usually referred to as large-cell calcifying Sertoli cell
      tumors (LSCT). OBJECTIVE: To evaluate the value of endocrine markers and
      aromatase inhibitor treatment in children with PJS and LSCT. DESIGN AND SETTING:
      Familial cases, followed in a tertiary care center. PATIENTS: Two male siblings
      aged 7 and 9 years with PJS and LSCT. INTERVENTION: Third generation aromatase
      inhibitor (anastrozole) in one of the patients. MAIN OUTCOME MEASURES:
      Longitudinal measurements of sex-steroids, gonadotropins, Sertoli cell markers
      and auxological evaluation. RESULTS: The two male siblings with PJS had similar
      bilateral multifocal testicular calcifications and biochemical evidence of
      Sertoli cell dysfunction manifested by elevated plasma inhibin-alpha levels. Only
      one sibling had gynecomastia. Estradiol levels were normal in both. During
      treatment with anastrozole, estradiol levels, growth and skeletal maturation, as
      well as Sertoli cell markers (inhibin B, inhibin-alpha and anti-Mullerian
      hormone) decreased. CONCLUSIONS: Inhibin-alpha may be considered as a marker for
      LSCT in children with PJS, pointing to a specific defect in inhibin regulation in
      this condition. Moreover, the decrease in Sertoli cell markers during aromatase
      inhibitor treatment suggests that increased estrogen production is a primary
      event regulating downstream production of Sertoli cell peptides. Anastrozole is
      efficient in controlling the clinical features of the disease and should be
      proposed as an alternative to bilateral orchidectomy, which is often performed in
      this condition.

PMID- 16452535
TI  - The role of thiocyanate in the etiology of goiter in an industrial metropolitan
      area.
AB  - OBJECTIVE: Thiocyanate (SCN-) has concentration dependent antithyroid properties
      and a role in the etiology of goiter has been suggested in several studies. In
      1991 an epidemiological survey conducted in the region of Halle/Leipzig (Saxony),
      an area with significant air pollution, suggested an inverse relationship between
      urinary iodine (I-)/SCN- excretion and goiter prevalence. 10 years later, we
      reinvestigated the same industrial area to clarify if the situation has changed
      after the elimination of most industrial waste products and moreover, if SCN-
      excretion levels alone or in combination with air pollution or smoking as a SCN-
      source are critical for thyroid function. DESIGN AND METHODS: We investigated a
      cohort of 708 probands for I-, SCN- and creatinine excretion in spot urine
      samples and determined the prevalence of goiter and thyroid nodules by high
      resolution ultrasonography. RESULTS: Probands with goiter (n = 79, 11%) had
      significantly higher urinary SCN- excretions than probands without (3.9 +/- 2.8
      vs 3.1 +/- 3.4 mg SCN-/g creatinine) and significantly lower urinary I-/SCN-
      ratios than patients without thyroid disorders (41 +/- 38 vs 61 +/- 71 microg I
      /mg SCN-/l). Mean urinary I- excretions were not different between probands with
      or without goiter. Smokers showed significantly elevated urinary SCN-/creatinine
      ratios in comparison to non-smokers (4.3 +/- 4.3 vs 2.4 +/- 2.1 mg SCN-/g
      creatinine). ANOVA revealed a prediction of thyroid volume through age (P <
      0.001), gender (P < 0.001), body weight (P < 0.05) and smoking (P < 0.05).
      CONCLUSIONS: In our investigation, age, gender and smoking (raising SCN- levels
      by CN- inhalation) were predictive for thyroid volume and the urinary I-/SCN-
      ratios were able to detect probands with an increased risk of developing goiter
      in contrast to urinary I- excretion levels alone. These data suggest, that in an
      era and area of decreased cyanide pollution, SCN- may remain a cofactor in the
      multifactorial aetiology of goiter.

PMID- 16452536
TI  - Fetal microchimerism in Hashimoto's thyroiditis: a quantitative approach.
AB  - OBJECTIVE: Fetal microchimerism (MCH) has been implicated in the etiology of
      autoimmune diseases such as autoimmune thyroiditis. The goal of the study was to
      reliably estimate the number of fetal engrafted cells and to further investigate
      factors influencing the development of MCH. METHODS: Quantitative real-time PCR
      amplification using Y-chromosome specific (DYS14) and autosomal (beta-globin)
      loci was performed on thyroid gland specimens. Furthermore, we compared the
      distribution of ABO and rhesus systems in mothers with and without blood MCH in
      relation to the blood groups of the children. RESULTS: MCH was detected in eight
      of 21 Hashimoto patients in a frequency range of 15 to 4900 male cells per
      100,000 total cells (median 97 cells), but in none of 17 healthy thyroid glands.
      In a third group, consisting of 18 nodular goiters, only one sample was positive
      (182 male cells/100,000 total cells). No woman who had not had a prior pregnancy
      with a male fetus showed MCH. Mothers both with and without MCH showed the same
      rate of mother/child incompatibilities for the ABO and rhesus systems.
      CONCLUSIONS: The percentage of microchimeric cells varies to a great extent in
      Hashimoto's thyroiditis, and this phenomenon can occur in nodular goiter in rare
      instances, but it appears to be absent from normal thyroid glands. Nevertheless,
      the biological significance of MCH remains unclear. Moreover, we have concluded
      that the tested blood group systems (as opposed to their role in graft vs host
      disease after transplantations) have no effect on fetal MCH.

PMID- 16452537
TI  - Low-dose recombinant human thyrotropin-aided radioiodine treatment of large,
      multinodular goiters in elderly patients.
AB  - OBJECTIVE: We aimed to assess low-dose recombinant human thyroid-stimulating
      hormone (rhTSH)-aided, fixed-activity radioiodine therapy of large, multinodular
      goiters (MNGs) in elderly patients with comorbidities. DESIGN: This was a short
      term, observational study. METHODS: We measured 24-h thyroid radioiodine uptake
      (RAIU) of 2 microCi 131-iodine at baseline and 24 h after intramuscular injection
      of 0.03 mg rhTSH in 17 patients (aged 60-86 years, 12 women), who subsequently
      received 30 mCi 131-iodine 24 h after an identical rhTSH injection. TSH and free
      thyroxine (FT4) were measured at baseline and days 10, 30 and 90 after therapy.
      Thyroid volume was assessed by computed tomography at baseline and day 180.
      RESULTS: rhTSH, 0.03 mg, significantly increased mean 24-h thyroid RAIU from
      25.8% +/- 10.3% to 43.3% +/- 8.4% (68% relative increase; t(16) = -8.43, P <
      0.001). The proportion of patients overtly or subclinically hyperthyroid (TSH <
      0.5 mU/l) decreased from 71% (12/17) at baseline to 19% (3/16) at 3 months. Mean
      serum FT4 peaked at slightly above normal range, 25.9 +/- 7.7 pmol/l (46% over
      baseline) and was 21% under baseline levels at 3 months. Mean estimated thyroid
      volume fell 34% from baseline to 6 months (170.0 +/- 112.8 to 113.1 +/- 97.5 ml;
      P < 0.01). Symptomatic relief, improved well-being, and/or reduction or
      elimination of antihyperthyroid medication were seen in 76% of patients. Three
      (18%) patients had transient neck pain or tenderness, or palpitations; one had
      transient asymptomatic thyroid enlargement; and three (18%) became hypothyroid by
      3 months. CONCLUSIONS: Intramuscular rhTSH, 0.03 mg, followed 24 h later by 30
      mCi 131-iodine, is a safe, effective and convenient treatment for MNG in elderly
      patients with comorbidities.

PMID- 16452538
TI  - Treatment of tall stature in boys with somatostatin analogue 201-995: effect on
      final height.
AB  - BACKGROUND: An optimal treatment for tall stature in boys in terms of efficacy
      and safety is not available. Treatment with somatostatin analogue 201-995 (SMS)
      has been tried with positive short-term results. METHODS: We evaluated the effect
      of SMS treatment on reducing adult height. Over 2 years, 16 boys presenting to
      our university hospital with tall stature (constitutional tall stature (n = 13),
      Marfan syndrome (n = 2) and tethered spinal cord (n = 1)) with a predicted final
      height above 197 cm were included in the study and prospectively followed until
      final height was reached. As one boy was lost to follow-up we have reported on 15
      boys. Treatment with SMS as a single subcutaneous dose was started and continued
      until final height was reached. In eight boys androgens were given to induce
      puberty after the start of SMS and five boys were on treatment with androgens
      prior to SMS treatment. Effect on reduction of final height prediction,
      calculated with the index of potential height based on the bone age of Greulich
      and Pyle, was the main outcome measure. Standard anthropometric assessments were
      performed a year before and every 3 months during treatment. Bone age was
      assessed by the method of Greulich and Pyle at the start and after 6 and 12
      months. RESULTS: Mean reduction in final height prediction (predicted adult
      height minus achieved adult height) was -0.1 cm (range -6.4 to +5.7). In three
      boys, asymptomatic microlithiasis of the gall bladder was diagnosed. CONCLUSIONS:
      We have concluded that, in spite of encouraging short-term results, long-term
      treatment with SMS does not reduce final height in a manner sufficient to justify
      SMS treatment in tall stature.

PMID- 16452539
TI  - Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic
      brain injury.
AB  - OBJECTIVE: Cross-sectional studies report a high prevalence of hypopituitarism
      after traumatic brain injury (TBI); however, no longitudinal studies on time of
      manifestation and reversibility exist. This study was conducted to assess
      hypopituitarism 3 and 12 months after TBI. DESIGN: This was a prospective,
      longitudinal, diagnostic study. METHODS: Seventy-eight patients (52 men, 26
      women, mean age 36.0 years) with TBI grades I-III and 38 healthy subjects (25
      men, 13 women, mean age 36.4 years) as a control group for the GHRH + arginine
      test were studied. The prevalence of hypopituitarism was assessed 3 and 12 months
      after TBI by GHRH + arginine test, short adrenocorticotropic hormone (ACTH) test,
      and basal hormone measurements in patients. RESULTS: After 3 months, 56% of all
      patients had impairments of at least one pituitary axis with axes being affected
      as follows: gonadotropic 32%, corticotropic 19%, somatotropic 9% and thyrotropic
      8%. After 12 months, fewer patients were affected, but in some cases new
      impairments occurred; 36% still had impairments. The axes were affected as
      follows after 12 months: gonadotropic 21%, somatotropic 10%, corticotropic 9% and
      thyrotropic 3%. CONCLUSIONS: Hypopituitarism occurs often in the post-acute phase
      after TBI and may normalize later, but may also develop after the post-acute
      phase of TBI.

PMID- 16452540
TI  - The octreotide test dose is not a reliable predictor of the subsequent response
      to somatostatin analogue therapy in patients with acromegaly.
AB  - In many centres, a test dose (TD) of octreotide is administered before commencing
      somatostatin analogue therapy (SAT), although the merits of this procedure are
      uncertain. We have analysed the value of the GH response to a TD in predicting
      the efficacy of subsequent SAT in 47 patients with acromegaly (25 male, median
      age 51 years, range 20-82). The primary goal of SAT was a mean GH of < 5 mU/l.
      Median baseline GH was 19.3 mU/l (2.2-233 mU/l) and with the TD fell by 78% (35
      98%) to a nadir of 4.2 mU/l (< 0.3-85 mU/l). Optimal predictive power was
      observed when GH fell to < 5 mU/l after the TD. With this criterion, the TD had a
      positive predictive value (PPV) of achieving the primary goal on SAT of 82% and a
      negative predictive value (NPV) of 50%. However, baseline GH was also highly
      predictive of the likelihood of successful SAT (GH < 5 mU/l). The GH response to
      the TD had PPV of 83% and NPV of 61% of normalising IGF-I on SAT. In summary,
      baseline GH and nadir after a TD are highly predictive of a good response to SAT;
      however, a poor response to a TD does not exclude an optimal response to SAT.
      Furthermore, failure to achieve biochemical control does not equate to no
      benefit, as biochemical improvement was seen in every patient; therefore, no
      patient should be deprived of octreotide therapy because of the result of a TD.
      In conclusion, our data indicate that the octreotide TD has no place in selecting
      patients for SAT.

PMID- 16452541
TI  - Celiac disease in North Italian patients with autoimmune Addison's disease.
AB  - OBJECTIVE: Patients with autoimmune Addison's disease (AAD) are prone to develop
      other autoimmune manifestations. An increased prevalence of celiac disease (CD)
      has recently been demonstrated in Northern European patients with AAD. IgA
      deficiency is the most frequent type of immunodeficiency among humans and is
      present in about one in every 600 individuals in the population. IgA deficiency
      is frequent in patients with other autoimmune diseases, but data concerning AAD
      are still unavailable. DESIGN: The aim was to define the prevalence of CD and of
      IgA deficiency in a group of Italian patients with AAD. METHODS: One hundred and
      nine patients with AAD were enrolled and examined for tissue transglutaminase
      autoantibodies of the IgA class, circulating levels of IgA and adrenal cortex
      antibodies. RESULTS: Two (1.8%) of the patients were affected by already
      diagnosed CD and were already on a gluten-free diet. Out of the remaining 107
      patients, four (3.7%) were found to be positive for IgA antibodies to human
      tissue transglutaminase. Three of the four patients who were positive for tissue
      transglutaminase autoantibodies agreed to undergo endoscopy and duodenal biopsies
      and, in one, a latent form of CD was identified. The clinical, silent or latent
      form of CD was present in six out of 109 (5.4%). This prevalence was
      significantly higher (P = 0.0001) than that reported for the Northern Italian
      population which was equal to 0.063%. Specifically, CD was present in 12.5% of
      the autoimmune polyglandular syndrome (APS) type 1 cases, in four out of 60
      (6.7%) of the APS type 2 cases and in one out of 40 (2.5%) of the isolated AAD
      cases. IgA deficiency was present in two out of 109 patients (1.8%), all of whom
      had normal IgG anti-gliadin. Autoantibodies to the adrenal cortex were detected
      in 81 out of 109 patients (74.3%). CONCLUSIONS: In patients with AAD there is a
      high prevalence of both CD and IgA deficiency. Consequently, it is important to
      screen for CD with tissue transglutaminase autoantibodies of the IgA class and
      for IgA levels.

PMID- 16452542
TI  - Maternal plasma corticotrophin-releasing factor and urocortin levels in post-term
      pregnancies.
AB  - OBJECTIVE: Corticotrophin-releasing factor (CRF) and urocortin are two placental
      neuropeptides that are involved in the mechanisms of labour by modulating
      myometrial activity. Maternal plasma levels of both CRF and urocortin are
      increased at term and preterm labour, whilst those of CRF are reduced in women
      who are destined to experience post-term delivery. The present study evaluated
      maternal plasma levels in term and post-term pregnancies out of labour. DESIGN: A
      group of healthy pregnant women was enrolled and subdivided as follows: (i) at
      term out of labour (n = 19; 276 +/- 0.7 days of gestation; samples collected at
      the time of elective caesarean section due to previous uterine surgery); (ii)
      post-term (n = 19; 291 +/- 1.4 days of gestation), from whom samples were
      collected before induction of labour. METHODS: Urocortin and CRF measurements by
      radioimmunoassay; digital palpatory cervical examination and Bishop score
      computation; cervical length and funnelling presence assessment by transvaginal
      ultrasonography. RESULTS: Maternal plasma CRF concentrations were significantly
      (P < 0.05) lower whilst those of urocortin were unchanged in post-term compared
      with term pregnancy. However, CRF and urocortin levels were both significantly (P
      < 0.05 and P < 0.001 respectively) higher in pregnancies delivered within 12 h of
      labour induction than in those that remained undelivered, and were significantly
      correlated with the induction-delivery interval (CRF: r = -0.676, P = 0.0015;
      urocortin: r = -0.783, P < 0.0001). CONCLUSIONS: CRF and urocortin levels are
      decreased and unchanged, respectively, in post-term pregnancy when compared with
      term pregnancy. Both CRF and urocortin correlate with the time of labour onset
      after induction. Since CRF derives from the placenta, and urocortin from the
      fetus, the concerted expression of these neuropeptides appears to be relevant in
      determining the length of human gestation.

PMID- 16452543
TI  - Decreased soluble leptin receptor levels in women with polycystic ovary syndrome.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with insulin resistance
      and a high incidence of obesity. Leptin, the product of the ob gene, is involved
      in the regulation of energy balance and obesity and circulates in both free and
      bound forms. The soluble leptin receptor (sOB-R) is the most important leptin
      binding protein, thus influencing the biologically active free leptin level.
      DESIGN: We assessed the correlation of metabolic and endocrine parameters with
      leptin and sOB-R levels in 122 PCOS women (aged 27 +/- 5.7 years) and 81 healthy
      controls (aged 25 +/- 4.0 years). METHODS: Leptin and sOB-R levels were measured
      using ELISA kits. In addition, anthropometric variables, body fat and endocrine
      parameters were evaluated and a glucose tolerance test performed to assess
      indices of insulin resistance and glucose metabolism. RESULTS: In PCOS patients,
      no correlation was found between leptin or sOB-R and parameters of hyper
      androgenism. However, as expected, body mass index (BMI), body fat, waist
      circumference and indices of insulin resistance were significantly correlated
      with leptin in PCOS subjects and controls. In a subgroup analysis of lean,
      overweight and obese PCOS patients, significant differences were found in leptin
      (29.7 +/- 20.7 vs 45.4 +/- 25.0 vs 67.7 +/- 28.8 ng/ml, P < 0.0001) and sOB-R
      (8.0 +/- 3.4 vs 6.4 +/- 2.5 vs 5.7 +/- 2.3 ng/ml, P < 0.05). Compared with BMI
      matched controls, lean PCOS patients had lower sOB-R levels (8.0 +/- 3.4 vs 12.7
      +/- 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 +/- 3.9 vs 2.8 +/-
      2.2, P = 0.0285). CONCLUSION: Taking into account that low sOB-R levels
      supposedly compensate diminished leptin action, PCOS per se might cause leptin
      resistance.

PMID- 16452544
TI  - Predictors of abnormal glucose metabolism in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a risk factor for type 2 diabetes
      mellitus and screening for abnormal glucose metabolism has been recommended by an
      oral glucose tolerance test (OGTT). This procedure is time-consuming and
      inconvenient, limiting its general use. Therefore, an easy method is wanted to
      separate PCOS women with normal from those with potentially abnormal glucose
      metabolism. DESIGN: Simple parameters obtained from 101 consecutive PCOS patients
      were assessed by receiver operating curve analysis for their ability to predict
      abnormal glucose metabolism. RESULTS: Comparing discriminating parameters at
      defined sensitivities revealed that, assessed by homeostasis model assessment
      (HOMA), insulin resistance (HOMA%S) had the highest specificity. At a cut-off
      point of 73.1%, HOMA%S had a sensitivity of 95.5% and a specificity of 51.9%.
      Applying this cut-off separated 59 women who had a high probability of abnormal
      glucose metabolism from 42 women who were at low risk (less than 2.5%). Fasting
      insulin was the second-best parameter and had a similar specificity. A screening
      strategy which applies HOMA%S or fasting insulin could almost halve the number of
      OGTTs by directing them to those PCOS women most likely to be suffering from
      abnormal glucose metabolism. The negative predictive value of this strategy was
      97%. The strategy was tested and confirmed in a second and independent cohort of
      264 PCOS women. CONCLUSIONS: HOMA%S, or to a lesser extent fasting insulin,
      appears to allow for stratified metabolic screening of PCOS women with OGTT.

PMID- 16452545
TI  - Bone mineral density and bone turnover in young adult survivors of childhood
      acute lymphoblastic leukaemia.
AB  - OBJECTIVE: Treatment for childhood leukaemia induces many risk factors for
      development of decreased bone mineral density (BMD). Physical activity is also
      known to affect BMD. The aim was to study BMD and markers of bone turnover in a
      well-defined group of survivors of acute lymphoblastic leukaemia (ALL) who had
      all reached final height as well as peak bone mass, taking both previous
      treatment and physical activity into consideration. DESIGN: All patients treated
      for ALL before the onset of puberty in the region of western Sweden, between 1973
      and 1985, in first remission were included. Thirty-five out of forty-seven
      patients aged 20-32 years participated. Nineteen patients had received cranial
      radiotherapy, and the median follow-up time was 20 years. METHODS: BMD was
      assessed using dual-energy X-ray absorptiometry (DEXA). Serum concentrations of
      markers of bone turnover were analysed. Physical performance was measured using a
      performance exercise capacity stress test. RESULTS: BMD was slightly reduced in
      lumbar spine (-0.4 SD), but not in femoral neck or total body. BMD in femoral
      neck was correlated to physical performance and dose of corticosteroid, but no
      correlation was found with spontaneous growth hormone (GH) secretion. Markers of
      bone turnover were also correlated to physical performance, but not to GH
      secretion. CONCLUSIONS: Physical fitness seems to be the most important factor in
      developing and preserving normal bone mineral density in ALL patients. We propose
      that lifestyle education promoting physical activity is encouraged from an early
      point in time for these patients.

PMID- 16452546
TI  - Systemic monocyte chemoattractant protein-1 concentrations are independent of
      type 2 diabetes or parameters of obesity: results from the Cooperative Health
      Research in the Region of Augsburg Survey S4 (KORA S4).
AB  - OBJECTIVE: Data on the relevance of monocyte chemoattractant protein (MCP)-1 in
      the pathophysiology of type 2 diabetes (T2D) and obesity are inconsistent. Since
      MCP-1 is produced by adipocytes and has been postulated to be involved in
      macrophage infiltration into adipose tissue, we wanted to test whether serum MCP
      1 levels were correlated with T2D or obesity. DESIGN AND METHODS: Out of 1653
      individuals aged 55 to 74 years participating in the population-based KORA Survey
      S4 (KORA/Cooperative Health Research in the Region of Augsburg) in Southern
      Germany, 236 patients with T2D, 242 subjects with impaired glucose tolerance and
      244 normoglycaemic controls matched for age and sex were analysed for circulating
      MCP-1 concentrations. RESULTS: MCP-1 serum concentrations were not associated
      with impaired glucose tolerance, type 2 diabetes or several parameters of
      obesity. Moreover, systemic MCP-1 levels were not significantly correlated with
      all but one (fasting triglycerides) of the biochemical markers tested.
      CONCLUSIONS: Our data indicate that MCP-1 levels are not associated with T2D and
      that the contribution of fat mass to systemic MCP-1 protein might be low,
      suggesting that the possible local pathogenic role of MCP-1 may not be reflected
      by increased systemic levels of MCP-1.

PMID- 16452547
TI  - Plasma adiponectin concentration and tumor necrosis factor-alpha system activity
      in lean non-diabetic offspring of type 2 diabetic subjects.
AB  - OBJECTIVE: There is growing evidence that adiponectin function is related to the
      pathogenesis of insulin resistance. Insulin resistance might be present even in
      lean subjects with a strong family history of type 2 diabetes. The aim of the
      study was to look for adiponectin's role in the pathogenesis of insulin
      resistance in offspring of type 2 diabetic patients, and its relation to the
      activity of the tumor necrosis factor (TNF)-alpha system. RESEARCH DESIGN AND
      METHODS: The study was carried out in 23 lean offspring of type 2 diabetic
      subjects and in 23 controls matched for age, sex and body mass index. The oral
      glucose tolerance test for glucose and insulin estimations and hyperinsulinemic,
      euglycemic clamp studies were performed in all patients. The plasma concentration
      of adiponectin, TNF-alpha, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c,
      total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density
      lipoprotein-cholesterol and triglycerides were estimated. RESULTS: The insulin
      sensitivity index, normalized for fat-free mass (M(ffm)) and adiponectin
      concentrations were markedly decreased in offspring of type 2 diabetic subjects
      compared with the control group (P = 0.0046 and P = 0.00058 respectively). TNF
      alpha and sTNFR1 concentrations did not differ between the studied groups;
      however the concentration of sTNFR2 was markedly increased in the offspring of
      type 2 diabetic patients (P = 0.0002). Adiponectin concentration was positively
      correlated to the insulin sensitivity index (r = 0.34; P = 0.020) and to HDL
      cholesterol (r = 0.29, P = 0.047) and was inversely related to sTNFR2 (r = -0.33,
      P = 0.027). CONCLUSIONS: The obtained results suggest that adiponectin could play
      a role in the pathogenesis of insulin resistance in lean offspring of type 2
      diabetic subjects.

PMID- 16452548
TI  - Cortisol correlates with metabolic disturbances in a population study of type 2
      diabetic patients.
AB  - OBJECTIVE: The prevalence of type 2 diabetes mellitus is increasing rapidly in
      industrialized countries, and adrenal glucocorticoids may intensify this disease.
      We sought to assess the relationship between diabetes-associated metabolic
      disturbances and cortisol concentrations in patients with type 2 diabetes.
      DESIGN: We investigated 190 type 2 diabetic patients who volunteered from a
      population study of 12,430 people in Luebeck and its suburbs. The target
      population comprised men and women born between 1939 and 1958 who initially
      received a postal questionnaire about their health status. We identified 346
      subjects with confirmed diabetes mellitus and 216 patients participated in the
      study. Patients with type 1 diabetes were excluded. METHODS: Five salivary
      cortisol samples were collected before and after lunch, in the evening and then
      the next morning before and after standing. Clinical variables associated with
      diabetes were measured and correlated with cortisol concentrations. RESULTS: None
      of the cohort had salivary cortisol concentrations that exceeded the normally
      accepted range. Based on cortisol samples collected just prior to a standard
      lunch, the cohort was divided into tertiles. Cortisol was positively related to:
      fasting blood, urinary and postprandial glucose; glycosylated hemoglobin; and
      systolic and diastolic blood pressures (all P < 0.05). Cortisol concentrations
      also correlated with the relative abdominal mass (P < 0.05) when patients with
      marked glucosuria were excluded. CONCLUSIONS: The degree of severity of several
      clinical measures of type 2 diabetes correlates with cortisol concentrations.
      Moreover, the results provide evidence for a positive relationship between
      metabolic disturbances and cortisol concentrations that are within the accepted
      normal range.

PMID- 16452549
TI  - Association between serum ferritin and the insulin resistance syndrome in a
      representative population.
AB  - OBJECTIVE: Unexplained hepatic iron overload with increased serum ferritin (SF)
      values has been associated with the insulin resistance syndrome (IRS), defined by
      the presence of one or more of the following criteria: increased body mass index
      (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association
      between IRS and SF in a representative population has not been investigated.
      METHODS: The study subjects participated in a nationwide epidemiological survey
      on metabolic disorders in the adult German population. The 1200 probands included
      in this study are representative of the German population. To eliminate major
      causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol
      consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C
      were excluded. For all remaining 1070 probands, complete clinical data of SF,
      HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and
      blood pressure were available. RESULTS: SF values were significantly increased in
      men and women with high BMI (> 25 kg/m2), increased cholesterol (> 200 mg/dl),
      and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and
      in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there
      was a significant correlation between the number of IRS criteria and SF.
      CONCLUSIONS: This study shows a significant correlation between SF and the
      presence of IRS criteria in a large representative population. Interestingly, the
      severity of the IRS seems to be associated with increased SF levels suggesting a
      causal connection. Further studies are required to investigate the
      pathophysiological mechanism and consequences of increased SF levels in patients
      with IRS.

PMID- 16452550
TI  - Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele
      specific PCR amplification (MASA).
AB  - OBJECTIVE: The somatic point mutation in the BRAF gene, which results in a valine
      to-glutamate substitution at residue 600 (BRAF(V600E)), is an ideal hallmark of
      papillary thyroid carcinoma (PTC). However, its prevalence is varyingly reported
      in different studies, and its expression in the follicular variant PTC is
      controversial, reducing its potential usefulness as diagnostic marker. DESIGN AND
      METHODS: We developed an assay based on mutant allele-specific PCR amplification
      (MASA) to detect BRAF mutation. We compared the sensitivity of MASA, single
      strand conformation polymorphism (SSCP) and direct DNA sequencing of PCR
      products. Then, we used MASA 78 to analyze 78 archival thyroid tissues, including
      normal samples, follicular adenomas, follicular carcinomas and PTC. RESULTS: The
      MASA assay proved to be a more sensitive method than SSCP and DNA sequencing of
      PCR products. BRAF mutation was found by MASA in 19/43 (44.2%) of PTC, including
      14/31 (45.2%) classic forms and 5/12 (41.7%) follicular variants. No mutations of
      BRAF were detected in the normal thyroid tissues, nor in follicular adenomas or
      follicular carcinomas. No correlation was found between BRAF mutation and
      clinicopathologic features nor with recurrence during a postoperative follow-up
      period of 4-11 years. BRAF(V600E) significantly correlated with absence of node
      metastasis. CONCLUSIONS: BRAF(V600E) is present in PTC, both in the classic form
      and in follicular variant with similar prevalence. No correlation was found
      between BRAF mutation and aggressive clinical behavior. MASA-PCR proved to be a
      specific, sensitive and reliable method to detect BRAF T1799A in DNA extracted
      from different sources, including cytologic samples obtained either fresh or from
      archival glass slides. We propose this method as a useful tool to improve
      accuracy of preoperative diagnosis identifying PTC from biopsies with
      indeterminate cytologic findings.

PMID- 16452551
TI  - Leukemia inhibitory factor reduces body fat mass in ovariectomized mice.
AB  - OBJECTIVE: Ovariectomized (OVX) mice are known to gain body fat while exposure to
      estrogens decreases fat mass. We have previously shown that estrogen replacement
      therapy enhances the expression of receptors for the cytokine, leukemia
      inhibitory factor (LIF). LIF and other cytokines acting via the gp130 signal
      transducing receptor have been reported to decrease obesity. In the present
      study, we investigated whether LIF treatment can reduce obesity in OVX mice.
      DESIGN: Eight-week-old female C57Bl/6 mice were OVX or sham-operated. The mice
      were treated with LIF, 30 microg/kg or PBS via daily i.p. injections for 15 days
      (n = 9-10). METHODS: Dual X-ray absorptiometry and computerized tomography.
      RESULTS: We found that LIF treatment of OVX mice caused a significant reduction
      in the weight of white fat depots (P = 0.017) and serum leptin levels (P =
      0.011). LIF also caused a significant decrease in brown fat mass (P = 0.036).
      Treatment with LIF decreased thymus weight but did not affect crown-rump length,
      femur length, trabecular bone mineral density or the weight of several non-fat
      organs including the uterus. CONCLUSION: The cytokine, LIF, decreases body fat
      mass in OVX mice, suggesting that estrogen signaling is not required for this
      effect.

PMID- 16452552
TI  - The direct effects of the angiotensin-converting enzyme inhibitors, zofenoprilat
      and enalaprilat, on isolated human pancreatic islets.
AB  - OBJECTIVE: Data from prospective studies suggest a significant reduction in the
      risk of new diabetes from drug therapies containing angiotensin-converting enzyme
      (ACE) inhibitors. Since the renin-angiotensin system (RAS) has been found locally
      in several tissues and cells, including pancreatic islets, we hypothesized that
      the positive metabolic effects of ACE inhibitors may be due to a beneficial
      action of these compounds on insulin-secreting beta-cells. DESIGN AND METHODS:
      Isolated human pancreatic islets were studied after 24 h of incubation with 22.2
      mmol/l glucose, with or without the presence in the incubation medium of 0.5-6.0
      mmol/l zofenoprilat or enalaprilat, ACE inhibitor drugs which differ by the
      presence of a sulphydryl or a carboxyl group in their structural formula.
      Functional and molecular studies were then performed to assess insulin secretion,
      redox balance, mRNA and protein expression. RESULTS: Angiotensinogen, ACE and
      angiotensin type 1 receptor mRNA expression increased in islets cultured in high
      glucose; this was similarly prevented by the presence of either ACE inhibitor. As
      expected, preculture of human islets in high glucose determined a marked
      reduction in insulin secretion which was associated with enhanced oxidative
      stress, as shown by increased nitrotyrosine concentrations, and enhanced
      expression of protein kinase C beta and NADPH oxidase. The presence of either of
      the ACE inhibitors counteracted several of the deleterious effects of high
      glucose exposure, including reduction of insulin secretion and increased
      oxidative stress; zofenoprilat showed significantly more marked effects.
      CONCLUSIONS: These results showed that: (a) RAS molecules are present in human
      islets and their expression is sensitive to glucose concentration, (b) ACE
      inhibitors, and in particular zofenoprilat, protect human islets from
      glucotoxicity and (c) the effects of ACE inhibition are associated with decreased
      oxidative stress. Together, these findings provide evidence that the possible
      beneficial effects of ACE inhibitors in human diabetes are due, at least in part,
      to a protective action on pancreatic beta-cells.

PMID- 16452553
TI  - Home testing for HIV.

PMID- 16452554
TI  - Unfinished business--expanding HIV testing in developing countries.

PMID- 16452555
TI  - Volunteering overseas--lessons from surgical brigades.

PMID- 16452556
TI  - Adopting orphan drugs--two dozen years of treating rare diseases.

PMID- 16452557
TI  - Intensive insulin therapy in the medical ICU.
AB  - BACKGROUND: Intensive insulin therapy reduces morbidity and mortality in patients
      in surgical intensive care units (ICUs), but its role in patients in medical ICUs
      is unknown. METHODS: In a prospective, randomized, controlled study of adult
      patients admitted to our medical ICU, we studied patients who were considered to
      need intensive care for at least three days. On admission, patients were randomly
      assigned to strict normalization of blood glucose levels (80 to 110 mg per
      deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to
      conventional therapy (insulin administered when the blood glucose level exceeded
      215 mg per deciliter [12 mmol per liter], with the infusion tapered when the
      level fell below 180 mg per deciliter [10 mmol per liter]). There was a history
      of diabetes in 16.9 percent of the patients. RESULTS: In the intention-to-treat
      analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels
      but did not significantly reduce in-hospital mortality (40.0 percent in the
      conventional-treatment group vs. 37.3 percent in the intensive-treatment group,
      P=0.33). However, morbidity was significantly reduced by the prevention of newly
      acquired kidney injury, accelerated weaning from mechanical ventilation, and
      accelerated discharge from the ICU and the hospital. Although length of stay in
      the ICU could not be predicted on admission, among 433 patients who stayed in the
      ICU for less than three days, mortality was greater among those receiving
      intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU
      for three or more days, in-hospital mortality in the 386 who received intensive
      insulin therapy was reduced from 52.5 to 43.0 percent (P=0.009) and morbidity was
      also reduced. CONCLUSIONS: Intensive insulin therapy significantly reduced
      morbidity but not mortality among all patients in the medical ICU. Although the
      risk of subsequent death and disease was reduced in patients treated for three or
      more days, these patients could not be identified before therapy. Further studies
      are needed to confirm these preliminary data. (ClinicalTrials.gov number,
      NCT00115479.)

PMID- 16452558
TI  - Human botulism immune globulin for the treatment of infant botulism.
AB  - BACKGROUND: We created the orphan drug Human Botulism Immune Globulin Intravenous
      (Human) (BIG-IV), which neutralizes botulinum toxin, and evaluated its safety and
      efficacy in treating infant botulism, the intestinal-toxemia form of human
      botulism. METHODS: We performed a five-year, randomized, double-blind, placebo
      controlled trial statewide, in California, of BIG-IV in 122 infants with
      suspected (and subsequently laboratory-confirmed) infant botulism (75 caused by
      type A Clostridium botulinum toxin, and 47 by type B toxin); treatment was given
      within three days after hospital admission. We subsequently performed a 6-year
      nationwide, open-label study of 382 laboratory-confirmed cases of infant botulism
      treated within 18 days after hospital admission. RESULTS: As compared with the
      control group in the randomized trial, infants treated with BIG-IV had a
      reduction in the mean length of the hospital stay, the primary efficacy outcome
      measure, from 5.7 weeks to 2.6 weeks (P<0.001). BIG-IV treatment also reduced the
      mean duration of intensive care by 3.2 weeks (P<0.001), the mean duration of
      mechanical ventilation by 2.6 weeks (P=0.01), the mean duration of tube or
      intravenous feeding by 6.4 weeks (P<0.001), and the mean hospital charges per
      patient by 88,600 dollars (in 2004 U.S. dollars; P<0.001). There were no serious
      adverse events attributable to BIG-IV. In the open-label study, infants treated
      with BIG-IV within seven days of admission had a mean length of hospital stay of
      2.2 weeks, and early treatment with BIG-IV shortened the mean length of stay
      significantly more than did later treatment. CONCLUSIONS: Prompt treatment of
      infant botulism type A or type B with BIG-IV was safe and effective in shortening
      the length and cost of the hospital stay and the severity of illness.

PMID- 16452559
TI  - Clozapine alone versus clozapine and risperidone with refractory schizophrenia.
AB  - BACKGROUND: The treatment of schizophrenia with multiple antipsychotic drugs is
      common, but the benefits and risks are not known. METHODS: In a randomized,
      double-blind study, we evaluated patients with schizophrenia and a poor response
      to treatment with clozapine. The patients continued to take clozapine and were
      randomly assigned to receive eight weeks of daily augmentation with 3 mg of
      risperidone or with placebo. This course of treatment was followed by an optional
      18 weeks of augmentation with risperidone. The primary outcome was reduction in
      the total score for severity of symptoms on the Positive and Negative Syndrome
      Scale (PANSS). The secondary outcomes included cognitive functioning. RESULTS: A
      total of 68 patients were randomly assigned to treatment. In the double-blind
      phase, the mean total score for the severity of symptoms decreased from baseline
      to eight weeks in both the risperidone and the placebo groups. There was no
      statistically significant difference in symptomatic benefit between augmentation
      with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34
      receiving risperidone responded to treatment (P=0.38). The mean difference in the
      change in PANSS scores from baseline to eight weeks between those receiving
      risperidone and those receiving placebo was 0.1 (95 percent confidence interval, 
      7.3 to 7.0). The verbal working-memory index showed a small decline in the
      risperidone group and a small improvement in the placebo group (P=0.02 for the
      comparison between the two groups in the change from baseline). The increase in
      fasting blood glucose levels was mildly greater in the risperidone group than in
      the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter],
      P=0.04). The incidence and severity of other side effects did not differ between
      the two groups. CONCLUSIONS: In this short-term study, the addition of
      risperidone to clozapine did not improve symptoms in patients with severe
      schizophrenia. (ClinicalTrials.gov number, NCT00272584).

PMID- 16452560
TI  - Coronary-artery stents.

PMID- 16452561
TI  - Positron-emission tomography and assessment of cancer therapy.

PMID- 16452562
TI  - Images in clinical medicine. A medical mystery--concentric calcification.

PMID- 16452563
TI  - Clinical problem-solving. Empirically incorrect.

PMID- 16452564
TI  - Intensive insulin in intensive care.

PMID- 16452565
TI  - The choice of drugs for schizophrenia.

PMID- 16452566
TI  - No stem cell is an islet (yet).

PMID- 16452567
TI  - MicroRNA in chronic lymphocytic leukemia.

PMID- 16452568
TI  - Response of glioblastomas to EGFR kinase inhibitors.

PMID- 16452569
TI  - Assessing EGFR mutations.

PMID- 16452570
TI  - The metrics of the physician brain drain.

PMID- 16452571
TI  - Health-information altruists.

PMID- 16452572
TI  - Magnetic resonance imaging and cerebrospinal fluid valves.

PMID- 16452573
TI  - Thiamine shortage--plight of low-cost, lifesaving orphan drugs.

PMID- 16452574
TI  - FEV6: a shortcut in spirometry?

PMID- 16452575
TI  - How can we improve our assessment of inflammation in clinical studies of COPD
      that use bronchial biopsies?

PMID- 16452576
TI  - Multimodality measurements of small airways disease.

PMID- 16452577
TI  - Identification of hBD-3 in respiratory tract and serum: the increase in
      pneumonia.
AB  - Human beta-defensin (hBD)-3, a 45 amino acid antimicrobial peptide, was
      originally isolated from human skin. hBD-3 mRNA has also been detected in the
      airways by RT-PCR. While hBD-3 may be involved in antimicrobial defences within
      the respiratory tract, the presence of hBD-3 peptide in the respiratory system
      has not yet been confirmed. The antimicrobial activity of the synthesised hBD-3
      peptide was measured by a radial diffusion assay and a colony count assay. The
      present authors confirmed the presence of hBD-3 peptide in homogenates of human
      lung and serum using reverse-phase HPLC coupled with a highly sensitive RIA. The
      localisation of the hBD-3 peptide was investigated by immunohistochemistry. In
      addition, the serum concentrations of hBD-3 were measured by RIA. hBD-3 exhibited
      a strong antimicrobial activity, which was unaffected by increasing salt
      concentrations. Immunohistochemically, the current authors observed the
      expression of hBD-3 in bronchial and bronchiolar epithelial cells. The mean+/-sd
      serum concentration of hBD-3 in patients with bacterial pneumonia was 239.4+/
      17.8 pg x mL(-1) in the acute phase and, decreased to 159.3+/-20.1 pg x mL(-1)
      after the completion of therapy. In conclusion, these findings will help
      elucidate the role of human beta-defensin-3 in host immune responses and identify
      the pathophysiological significance of this molecule in respiratory infections.

PMID- 16452578
TI  - Computed tomographic estimation of lung dimensions throughout the growth period.
AB  - The aim of the current study was to use computed tomography (CT) to estimate
      airway wall and lumen, and arterial and parenchyma dimensions in children
      throughout the growth period, and to provide normative data to study alterations
      caused by pulmonary disease. Clinical CT scans reported as normal that were
      performed in children for nonpulmonary and noncardiac reasons were analysed for
      lung weight, gas volume, lung expansion, lung surface/volume ratio, airway wall
      area, airway lumen area, airway lumen perimeter, arterial area and airway surface
      length/area ratio. The age range of the 50 subjects was 0-17.2 yrs. The data
      showed only little increase in lung expansion throughout childhood (n = 32).
      There was substantial variability in lung expansion between subjects. Airway wall
      and lumen and arterial area were exponentially associated with subjects' height
      (n = 50). Airway surface length/area ratio was linearly associated to alveolar
      surface/volume ratio. The data from the current study provide normative computed
      tomography estimates of airway wall and lumen, and arterial and parenchyma
      dimensions throughout the growth period that may be useful for the study of
      alterations in disease.

PMID- 16452579
TI  - Assessment of right ventricular function by strain rate imaging in chronic
      obstructive pulmonary disease.
AB  - The purpose of the current study was to compare right ventricular (RV) myocardial
      wall velocities (tissue Doppler imaging) and strain rate imaging (SRI) parameters
      with conventional echocardiographic indices evaluating RV function in chronic
      obstructive pulmonary disease (COPD) patients. In total, 39 patients with COPD
      and 22 healthy subjects were included in the current study. Seventeen patients
      had pulmonary artery pressure <35 mmHg (group I) and 22 patients had pulmonary
      artery pressure >35 mmHg (group II). Tissue Doppler imaging, strain and strain
      rate (SR) values were obtained from RV free wall (FW) and interventricular
      septum. Respiratory function tests were performed (forced expiratory volume in
      one second/vital capacity (FEV(1)/VC) and carbon monoxide diffusion lung capacity
      per unit of alveolar volume (D(L,CO)/V(A))). Strain/SR values were reduced in all
      segments of group II patients compared with group I patients and controls with
      lowest values at basal FW site. A significant relationship was shown between peak
      systolic SR at basal FW site and radionuclide RV ejection fraction. A significant
      relationship was shown between peak systolic SR at basal FW site and D(L,CO)/V(A)
      and FEV(1)/VC. In conclusion, in chronic obstructive pulmonary disease patients,
      strain rate imaging parameters can determine right ventricular dysfunction that
      is complementary to conventional echocardiographic indices and is correlated with
      pulmonary hypertension and respiratory function tests.

PMID- 16452581
TI  - Antioxidant intake, GSTM1 polymorphism and pulmonary function in healthy young
      adults.
AB  - Dietary antioxidants may protect lung tissue against reactive oxygen species
      induced injury, adverse respiratory effects and reduced pulmonary function.
      Genetic variability in antioxidant enzymes also determines response to oxidative
      stress in the lung. The current authors evaluated whether lung function levels
      are associated with dietary intake of antioxidants and the glutathione S
      transferase M1 (GSTM1) polymorphism. The current study cohort consisted of
      healthy, nonsmoking freshmen students who were lifetime residents in the Los
      Angeles or the San Francisco Bay areas (CA, USA). Participants completed
      comprehensive residential history, health history and food frequency
      questionnaires. Blood for genotyping was collected and forced expiratory volume
      measurements were obtained. Dietary vitamin C, magnesium and daily fruit servings
      were associated positively with forced expiratory volume in one second in males
      and with maximum mid-expiratory flow, forced expiratory flow after 75% of
      expelled volume, and the ratio of maximum mid-expiratory flow to forced vital
      capacity in females. In multivariable regression, vitamin C (or fruit for male
      students) and magnesium showed a consistent, positive association with lung
      function. Among healthy female adolescents, dietary intake of vitamin C is
      associated with increased levels of lung function. The current study does not
      support a role for the glutathione S-transferase M1-null genotype as an
      independent risk factor for decrements in lung function.

PMID- 16452580
TI  - Endobronchial ultrasound and positron emission tomography positive mediastinal
      lymph nodes.
AB  - Positron emission tomography with 18F-fluoro-2-deoxy-d-glucose (FDG-PET) is more
      accurate than computed tomography for staging of mediastinal (hilar) lymph nodes.
      In the case of positive findings, tissue sampling of lymph nodes is required. The
      diagnostic/staging yield of transbronchial needle aspiration (TBNA) following
      endobronchial ultrasound (EBUS) localisation was assessed in this particular
      clinical setting. The number of avoided surgical procedures was evaluated. All
      consecutive patients referred for staging and/or diagnosis of mediastinal FDG-PET
      positive lesions were included. Data were prospectively collected. TBNA sampling
      of lymph nodes was performed after EBUS localisation. If no diagnosis was
      reached, further surgical sampling or adequate follow-up was performed. From
      January 2003 to June 2004, 33 patients were included. The average number of TBNA
      samples per patient was 4.2+/-1.5. Cytological or histological diagnoses were
      obtained in 27 (82%) of the patients, of which 78% were obtained after previous
      EBUS localisation. In 25 (76%) of the 33 patients, surgical staging procedures
      were suppressed. In conclusion, transbronchial needle aspiration after
      endobronchial ultrasound localisation should be considered as a primary method of
      evaluation of lymph nodes positive by positron emission tomography with 18F
      fluoro-2-deoxy-d-glucose, and may replace the majority of surgical mediastinal
      staging/diagnostic procedures.

PMID- 16452582
TI  - Limitation of cigarette consumption by CYP2A6*4, *7 and *9 polymorphisms.
AB  - The whole gene deletion CYP2A6*4, the defect of the main nicotine oxidase,
      contributes to limiting lifelong and daily cigarette consumption. However, the
      effects on smoking habits of CYP2A6*7 and *9, two major functional polymorphisms
      common in Asian populations, have not been reported. The present study examined
      the relationship between polymorphisms *4, *7 and *9 with the smoking habits of
      200 Japanese smokers who visited the Keio University Hospital (Tokyo, Japan). The
      allele frequencies of *1 (wild type), *4, *7 and *9 were 52, 17, 11 and 20%,
      respectively. When the three polymorphisms were considered simultaneously, the
      percentages of homozygous wild type, heterozygote, and homozygous mutants and
      compound heterozygotes were 26.0, 52.5 and 21.5%, respectively. Homozygous
      mutants and compound heterozygotes (n = 43) smoked fewer cigarettes daily than
      heterozygotes (n = 105) and homozygous wild-type individuals (n = 52). Smokers
      with *7/*7, *9/*9 or *7/*9 had lower daily cigarette consumption than smokers
      with *1/*1. In conclusion, polymorphisms *4, *7 and *9 of CYP2A6 were detected in
      approximately three out of four Japanese smokers, and their daily cigarette
      consumption was genetically modulated by these functional polymorphisms.

PMID- 16452583
TI  - Variability of bronchial inflammation in chronic obstructive pulmonary disease:
      implications for study design.
AB  - There is variability in the distribution of inflammatory cells in bronchial
      tissue in chronic obstructive pulmonary disease (COPD). Better strategies for
      biopsy sampling of the airway mucosa may improve the capacity to show a
      difference between study populations where variability in distribution exists.
      The current authors have examined sources of biological variability in the
      quantification of inflammatory cells in endobronchial biopsies using
      immunostained samples taken from 51 subjects with COPD, with a mean forced
      expiratory volume in one second of 1.71 L, 55% predicted. The distribution of
      variance contributed by different sources was similar for different inflammatory
      cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest
      contribution to intra-subject variability (39%) was time (i.e. 10 weeks between
      biopsies of placebo-treated subjects), followed by airway generation (23%),
      biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations
      demonstrated that examining one section from one biopsy, from each of two airway
      generations, would require a sample size of 32 subjects per group to show a
      difference of one doubling or halving in CD8+ cells, compared with 47 subjects
      per group if only one airway generation was sampled. Therefore, biopsies from
      more than one airway generation should be examined in order to maximise
      statistical power to detect a difference between study groups.

PMID- 16452584
TI  - Stability of housekeeping genes in alveolar macrophages from COPD patients.
AB  - The stability of housekeeping genes is critical when performing gene expression
      studies. To date, there have been no studies that look at the stability of
      commonly used housekeeping genes in alveolar macrophages. Expression levels may
      be affected by culture, stimulation or disease severity. The present study
      investigated the expression level of 10 housekeeping genes and analysed the
      stability of their expression in alveolar macrophages from chronic obstructive
      pulmonary disease patients (n = 22) who were classified according to disease
      severity. Guanine nucleotide-binding protein, beta polypeptide 2-like 1 (GNB2L1),
      hypoxanthine phosphoribosyl transferase 1 (HPRT1) and ribosomal protein L32
      (RPL32) were the most stably expressed in alveolar macrophages, irrespective of
      disease severity. There was no difference in the expression levels of 10
      housekeeping genes between mild and moderate/severe patients. GNB2L1, HPRT1 and
      RPL32 were also stably expressed in alveolar macrophages cultured with no
      stimulation, or with interleukin-1beta, lipopolysaccharide or tumour necrosis
      factor-alpha stimulation. In conclusion, as fluctuations in the expression of
      some housekeeping genes were observed, including glyceraldehyde-3-phosphate
      dehydrogenase, it is recommended that guanine nucleotide binding protein, beta
      polypeptide 2-like 1 be used as a reference gene for alveolar macrophages in
      similar study designs, or that the stability of housekeeping genes be validated
      in alveolar macrophages prior to expression studies.

PMID- 16452585
TI  - Montelukast improves regional air-trapping due to small airways obstruction in
      asthma.
AB  - Quantitative image analysis of high-resolution computed tomography (HRCT)
      performed at residual volume, before and after methacholine, is a sensitive
      method of detecting small airways involvement in asthma and response to therapy
      targeted to the small airways. Since an oral anti-leukotriene reaches the small
      airways via the circulation, the present authors hypothesised that treatment with
      montelukast would lead to improved small airway patency. A double-blind crossover
      study compared the effect of montelukast versus placebo for 4 weeks in 16 mild-to
      moderate steroid-naive asthmatics. Small airways function was evaluated by HRCT
      at residual volume before and after methacholine to assess regional air-trapping
      and airways hyperresponsiveness, as well as by physiological studies of small
      airways. Montelukast treatment resulted in significantly less regional air
      trapping on HRCT on the pre-methacholine images when compared with placebo, as
      well as improvement in total quality of life scores and symptom sub-scores.
      However, montelukast treatment had no effect on increases in regional air
      trapping on HRCT in response to methacholine. No differences were noted in global
      measures of small airways physiology between placebo and montelukast. In
      conclusion, distal airways disease improves in asthmatic subjects treated with
      montelukast. This improvement can be detected with high-resolution computed
      tomography, but not with conventional physiological studies.

PMID- 16452586
TI  - The effect of inhaled budesonide on adrenal and growth suppression in asthmatic
      children.
AB  - The present authors evaluated adrenal reserve in asthmatic children on long-term
      inhaled corticosteroids and whether possible adrenal suppression could be
      predicted by growth retardation. Low-dose synacthen test (0.5 microg x 1.73 m(
      2)) was performed in 72 asthmatic children with a median age of 9.4 (range 4.2
      15.7) yrs on long-term treatment (median 18 (range 6-84) months) with low-to
      moderate doses (median 363 (range 127-1012) microg x m(-2)) of inhaled
      budesonide, as well as in 30 controls. Adrenal suppression was considered as a
      peak serum cortisol <495 nmol x L(-1). The current authors calculated height
      standard deviation score (HSDS) at the time of testing and height velocity SDS
      (HVSDS) in the preceding year. Mean HSDS was 0.06+/-1.3 and HVSDS was -0.9+/-2.3.
      Adrenal suppression was disclosed in 15 asthmatic children (20.8%). There were no
      differences in HSDS and HVSDS between children with and without adrenal
      suppression. There was no correlation between peak cortisol response and dose or
      duration of treatment. However, a positive relationship between HVSDS and
      duration of treatment was noted. These data suggest that long-term treatment of
      asthmatic children with low and moderate doses of inhaled budesonide may result
      in mild adrenal suppression that cannot be predicted by growth deceleration. The
      negative influence of inhaled corticosteroids on growth becomes less the longer
      the duration of treatment.

PMID- 16452587
TI  - Sleep-disordered breathing and upper airway size in pregnancy and post-partum.
AB  - Sleep-disordered breathing and snoring are common in pregnancy. The aim of this
      study was to determine whether pregnancy was associated with upper airway
      narrowing. One-hundred females in the third trimester of pregnancy were recruited
      and 50 agreed to be restudied 3 months after delivery. One-hundred nonpregnant
      females were also recruited. Upper airway dimensions were measured using acoustic
      reflection. Snoring was less common in nonpregnant (17%) than pregnant females
      (41%; odds ratio (OR) 3.34; 95% confidence interval (CI) 1.65-6.74) and returned
      to nonpregnant levels after delivery (18%; OR 0.15; 95% CI 0.06-0.40). Pregnant
      females had significantly smaller upper airways than nonpregnant females at the
      oropharyngeal junction when seated (mean difference 0.12; 95% CI 0.008-0.25), and
      smaller mean pharyngeal areas in the seated (mean difference 0.14; 95% CI 0.001
      0.28), supine (mean difference 0.11; 95% CI 0.01-0.22) and lateral postures (mean
      difference 0.13; 95% CI 0.02-0.24) compared with the nonpregnant females.
      Pregnant females had smaller mean pharyngeal areas compared with post-partum in
      the seated (mean difference 0.18; 95% CI 0.02-0.32), supine (mean difference
      0.20; 95% CI 0.06-0.35) and lateral postures (mean difference 0.26; 95% CI 0.12
      0.39). In conclusion, this study confirmed increased snoring and showed narrower
      upper airways during the third trimester of pregnancy.

PMID- 16452588
TI  - Pre-eclampsia is associated with sleep-disordered breathing and endothelial
      dysfunction.
AB  - Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction
      (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with
      PET would demonstrate both SDB and ED, and that a correlation between these two
      would suggest a potential causative association. A total of 17 females with PET
      and 25 matched females with uncomplicated pregnancy were studied. They underwent
      a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive
      evaluation of endothelial function utilising the reactive hyperaemia test (using
      Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude
      (endothelial function index (EFI)) indicated better endothelial function. Females
      with PET had a significantly higher respiratory disturbance index (RDI) and lower
      EFI than controls (18.4+/-8.4 versus 8.3+/-1.3.h(-1), and 1.5+/-0.1 versus 1.8+/
      0.1, respectively). Blood pressure significantly correlated with RDI and with
      EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that
      both sleep-disordered breathing and endothelial dysfunction are more likely to
      occur in females with pre-eclamptic toxaemia than in females with uncomplicated
      pregnancies. The current authors speculate that respiratory disturbances
      contribute to the functional abnormality of the blood vessels seen in females
      with pre-eclamptic toxaemia, although causality cannot be determined based on
      this study.

PMID- 16452589
TI  - Diaphragm electromyograms recorded from multiple surface electrodes following
      magnetic stimulation.
AB  - The diaphragm compound-muscle action potential (CMAPdi), elicited by unilateral
      magnetic stimulation (UMS) of the phrenic nerve can be recorded using surface
      electrodes. However, there is no consensus on the best positioning of surface
      electrodes and there are no data on the reproducibility of the signal. Using 36
      surface electrode pairs, in five healthy subjects, the CMAPdi elicited by UMS and
      electrical stimulation (ES) were compared and 12 pairs were identified as
      providing acceptable signals. The latency and amplitude were measured for each
      CMAPdi, following UMS at 60-100% of maximal stimulator output, in 12 healthy
      subjects, on two occasions. Latencies obtained using UMS and ES ranged between
      6.1-7.33 and 6.25-7.17 ms, respectively. Optimum CMAPdi were not recorded from
      the same electrode pair in all subjects, or for both hemidiaphragms in each
      subject. However, the optimal recording site for a particular individual remained
      unchanged on subsequent testing. When recorded from the optimal site, latencies
      and amplitudes of CMAPdi elicited on the two occasions were not significantly
      different. The current study suggests that the use of multiple chest wall
      electrodes can identify an optimal electrode pair, from which it is possible to
      obtain reproducible compound-muscle action potential signals.

PMID- 16452590
TI  - Maximal inspiratory and expiratory pressure measurement in tracheotomised
      patients.
AB  - The present study compared four different sites and conditions for the
      measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure
      (MEP) in 38 spontaneous breathing tracheotomised patients. Of the patients, 28
      had chronic obstructive pulmonary disease (COPD). The four different conditions
      were: 1) through a cuff inflated cannula (condition A); 2) through the mouth with
      a deflated cannula (condition B); 3) through the mouth with a phonetic uncuffed
      cannula (condition C); and 4) through the mouth after stoma closure (condition
      D). Five trials in each condition were performed using a standardised method. The
      measurement of both MIP and MEP differed significantly depending on the condition
      of measurement. MIP taken in condition A was significantly higher when compared
      with conditions B, C and D. MEP in condition A was significantly higher when
      compared with condition B and D. In condition A the highest frequency of the best
      measurement of MIP and MEP was observed at the fourth and fifth effort,
      respectively. The same results were obtained after the selection of only COPD
      patients. In conclusion, respiratory muscle assessment differs significantly
      depending on measurement condition. Measurement through inflated cannula
      tracheotomy yields higher values of both maximal inspiratory and maximal
      expiratory pressure.

PMID- 16452591
TI  - Exhaled nitric oxide is not reduced in infants with cystic fibrosis.
AB  - Fractional exhaled nitric oxide (F(eNO)) has been reported to be reduced in
      cystic fibrosis (CF) patients. However, data from young children are conflicting
      and it is not clear whether this is a primary feature of the disease or a
      secondary response. The present study compared F(eNO) between CF and healthy
      infants using a validated single-breath technique. A total of 23 healthy infants
      (11 females; mean age 40.1 weeks) and 18 infants with CF (nine females; 64.9
      weeks) underwent tests of lung function and F(eNO). Bronchoalveolar lavage (BAL)
      was collected from all CF infants 2-5 days after lung function testing. There was
      no significant difference in F(eNO) between the CF and healthy infants (geometric
      mean: 23.1 parts per billion (ppb) and 17.0 ppb, respectively). There was an
      inverse relationship between age and F(eNO) in the CF patients, but not in the
      healthy group. Within the CF group, there was no association between F(eNO) and
      any marker of airway inflammation measured in the BAL. Exhaled nitric oxide is
      not reduced in cystic fibrosis infants, but does decrease with age. The current
      data indicate that F(eNO) is not a good marker of airway inflammation in cystic
      fibrosis.

PMID- 16452592
TI  - Inhaled heparin in cystic fibrosis.
AB  - Cystic fibrosis (CF) is characterised by inspissated airway secretions and
      chronic endobronchial infection associated with exuberant neutrophilic
      inflammation. Unfractionated heparin may be mucolytic and has demonstrated a
      number of anti-inflammatory properties; however, further safety data are needed
      in these subjects who are at risk of airway bleeding. The current study aimed to
      assess the medium-term safety and tolerability of moderately high-dose inhaled
      heparin in CF adults and to explore possible in vivo mucolytic and anti
      inflammatory outcomes. A randomised, double-blind, placebo-controlled crossover
      study of twice daily inhalation of 50,000 IU of heparin for 2 weeks was
      undertaken in CF adults, with a 1-week washout period. Eighteen subjects were
      randomised and 14 (mean+/-sd age 23+/-7.8 yrs and percentage-predicted forced
      expiratory volume in one second 52.1+/-15.56%) completed the study protocol.
      Heparin neither affected blood coagulation parameters nor resulted in any
      increase in adverse events. Heparin inhalation had no significant effect upon
      forced expiratory volume in one second, symptoms of sputum clearance or sputum
      inflammatory markers. The current pilot study demonstrated no evidence of
      improved sputum clearance with 50,000 IU of inhaled heparin given twice daily to
      adult cystic fibrosis subjects. However, inhaled heparin was safe and the future
      evaluation of larger doses over a longer period may be warranted.

PMID- 16452593
TI  - Airway antioxidant and inflammatory responses to diesel exhaust exposure in
      healthy humans.
AB  - Pulmonary cells exposed to diesel exhaust (DE) particles in vitro respond in a
      hierarchical fashion with protective antioxidant responses predominating at low
      doses and inflammation and injury only occurring at higher concentrations. In the
      present study, the authors examined whether similar responses occurred in vivo,
      specifically whether antioxidants were upregulated following a low-dose DE
      challenge and investigated how these responses related to the development of
      airway inflammation at different levels of the respiratory tract where particle
      dose varies markedly. A total of 15 volunteers were exposed to DE (100 microg x
      m(-3) airborne particulate matter with a diameter of <10 microm for 2 h) and air
      in a double-blinded, randomised fashion. At 18 h post-exposure, bronchoscopy was
      performed with lavage and mucosal biopsies taken to assess airway redox and
      inflammatory status. Following DE exposure, the current authors observed an
      increase in bronchial mucosa neutrophil and mast cell numbers, as well as
      increased neutrophil numbers, interleukin-8 and myeloperoxidase concentrations in
      bronchial lavage. No inflammatory responses were seen in the alveolar
      compartment, but both reduced glutathione and urate concentrations were increased
      following diesel exposure. In conclusion, the lung inflammatory response to
      diesel exhaust is compartmentalised, related to differing antioxidant responses
      in the conducting airway and alveolar regions.

PMID- 16452595
TI  - FEV6 as a surrogate for FVC in detecting airways obstruction and restriction in
      the workplace.
AB  - Compared with measurements of forced vital capacity (FVC), using the forced
      expiratory volume in six seconds (FEV(6)) reduces test time and frustration. It
      was hypothesised that using FEV(6) in the workplace setting would result in an
      acceptably low misclassification rate for detecting airways obstruction and
      spirometry-defined restriction when compared with using the traditional FVC.
      Experienced technicians from the National Institute for Occupational Safety and
      Health performed spirometry using dry rolling-seal spirometers as per American
      Thoracic Society guidelines in four workplace investigations. Airways obstruction
      was defined as an FEV(1)/FVC % below the lower limit of normal (LLN) using
      National Health and Nutrition Examination Survey III reference equations.
      Restriction was defined as an FVC below the LLN with a normal FEV(1)/FVC %. These
      "gold standard" definitions were compared with definitions based on FEV(6)
      (obstruction: FEV(1)/FEV(6) below the LLN; restriction: FEV(6) below the LLN with
      a normal FEV(1)/FEV(6)). The median (range) age of the 1,139 workers was 37 yrs
      (18-71 yrs) and 51.4% were male. A significantly high overall agreement was
      obtained between the two definitions. In conclusion, the current results confirm
      that forced expiratory volume in six seconds can be used as a surrogate for
      forced vital capacity in detecting airways obstruction and restriction in
      workers, although with some misclassification when compared to obtaining American
      Thoracic Society-acceptable manoeuvres of longer duration.

PMID- 16452594
TI  - Inflammatory responses to the occupational inhalation of metal fume.
AB  - Occupational exposure to metal fume promotes a reversible increase in the risk of
      pneumonia, but by mechanisms which are unclear. To investigate, the current
      authors measured various markers of host defence function in welders and
      nonwelders. Induced sputum and venous blood samples were collected from 27
      welders with regular long-term exposure to ferrous metal fume and 31 unexposed
      matched controls. In sputum, the present authors measured cell counts, the
      soluble and cellular iron concentration, and levels of interleukin-8, tumour
      necrosis factor-alpha, myeloperoxidase, matrix metalloproteinase-9,
      immunoglobulin (Ig)A, alpha(2)-macroglobulin and unsaturated iron-binding
      capacity. Blood samples were assayed for evidence of neutrophil activation and
      pneumococcal IgG antibodies. Welders had significantly higher iron levels and a
      substantially lower unsaturated iron-binding capacity in their sputum, but,
      despite a high iron challenge, there was a noteworthy absence of an inflammatory
      response. Only blood counts of eosinophils and basophils were significantly
      related to the extent of welding. Weak nonsignificant trends were observed for
      several other measures, consistent with low-grade priming of neutrophils. In
      conclusion, these data suggest that chronic exposure to metal fume blunts
      responsiveness to inhaled particulate matter. However, the mechanism behind the
      lack of detectable local inflammatory response requires further investigation.

PMID- 16452596
TI  - Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6
      and FEV6.
AB  - The purpose of this study was to determine fixed cut-off points for forced
      expiratory volume in one second (FEV(1))/FEV(6) and FEV(6) as an alternative for
      FEV(1)/forced vital capacity (FVC) and FVC in the detection of obstructive and
      restrictive spirometric patterns, respectively. For the study, a total of 11,676
      spirometric examinations, which took place on Caucasian subjects aged between 20
      80 yrs, were analysed. Receiver-operator characteristic curves were used to
      determine the FEV(1)/FEV(6) ratio and FEV(6) value that corresponded to the
      optimal combination of sensitivity and specificity, compared with the commonly
      used fixed cut-off term for FEV(1)/FVC and FVC. The data from the current study
      indicate that FEV(1)/ FEV(6) <73% and FEV(6) <82% predicted can be used as a
      valid alternative for the FEV(1)/FVC <70% and FVC <80% pred cut-off points for
      the detection of obstruction and restriction, respectively. The statistical
      analysis demonstrated very good, overall, agreement between the two
      categorisation schemes. For the spirometric diagnosis of airway obstruction
      (prevalence of 45.9%), FEV(1)/FEV(6) sensitivity and specificity were 94.4 and
      93.3%, respectively; the positive and negative predictive values were 92.2 and
      95.2%, respectively. For the spirometric detection of a restrictive pattern
      (prevalence of 14.9%), FEV(6) sensitivity and specificity were 95.9 and 98.6%,
      respectively; the positive and negative predictive values were 92.2 and 99.3%,
      respectively. This study demonstrates that forced expiratory volume in one
      second/forced expiratory volume in six seconds <73% and forced expiratory volume
      in six seconds <82% predicted, can be used as valid alternatives to forced
      expiratory volume in one second/forced vital capacity <70% and forced vital
      capacity <80% predicted, as fixed cut-off terms for the detection of an
      obstructive or restrictive spirometric pattern in adults.

PMID- 16452597
TI  - Laryngeal ultrasound: a useful method in predicting post-extubation stridor. A
      pilot study.
AB  - The cuff-leak test was widely used for the prediction of post-extubation stridor,
      but controversial results limit its clinical application. The current study used
      real-time ultrasonography to evaluate the air-leak and hypothesised that the air
      column width, measured by ultrasonography, may be correlated to the development
      of post-extubation stridor. From June 1, 2001 to March 1, 2002, a total of 51
      planned extubations in 51 consecutively intubated patients were included. All of
      the patients received ultrasonographical examinations of their vocal cords and
      larynx in addition to an air-column width measurement within 24 h prior to
      extubation. The overall post-extubation stridor rate was 7.8%. The air-leak
      volume presented as median (interquartile range) were 300 (350) mL and 25 (20)
      mL, respectively, for the nonstridor and stridor groups. The air-column width
      during cuff deflation was 6.4 (2) mm and 4.5 (0.8) mm, respectively. They were
      found to be statistically significant. In conclusion, the authors demonstrated
      that laryngeal ultrasonography could be a reliable, noninvasive method, in the
      evaluation of vocal cords, laryngeal morphology and the ease of airflow, which
      passed through vocal cords or subglottic area due to laryngeal oedema. The air
      column width during cuff deflation was a potential predictor of post-extubation
      stridor.

PMID- 16452598
TI  - The potential impact of anaemia of chronic disease in COPD.
AB  - Anaemia of chronic disease (ACD), with chronically low levels of circulating
      haemoglobin, is an immune driven abnormality that occurs in many inflammatory
      diseases, and also in chronic heart failure. Although chronic obstructive
      pulmonary disease (COPD) is "traditionally" associated with polycythaemia, the
      systemic inflammation that is now recognised as a feature of COPD makes it a
      possible cause of ACD. If present in COPD, anaemia could worsen dyspnoea and
      limit exercise tolerance. Preliminary evidence suggests that anaemia in COPD
      patients may be more prevalent than expected, concerning 10-15% of patients
      suffering from severe forms of the disease. A database study conducted in 2,524
      COPD patients being prescribed long-term oxygen therapy has shown that a low
      haematocrit is a strong predictor of survival in this population, before body
      mass index, and is associated with more hospitalisations and a longer cumulative
      duration of hospitalisation. COPD patients with low haemoglobin levels have a
      poorer prognosis than COPD patients with normal haemoglobin levels in the event
      of acute gastrointestinal bleeding or after elective aneurysm repair. Raising
      haemoglobinaemia through transfusion decreases minute ventilation and work of
      breathing in COPD patients. These preliminary evidences point to the need to
      study the prevalence of anaemia, and its physiological and clinical impact in
      chronic obstructive pulmonary disease. When this body of knowledge is available,
      the question of the putative benefits of raising haemoglobinaemia in chronic
      obstructive pulmonary disease will have to be addressed.

PMID- 16452599
TI  - Chronic obstructive pulmonary disease: current burden and future projections.

PMID- 16452600
TI  - Corticosteroid effects on cell signalling.
AB  - Corticosteroids are the most effective anti-inflammatory therapy for asthma.
      Inflammation in asthma is characterised by the increased expression of multiple
      inflammatory genes regulated by pro-inflammatory transcription factors, such as
      nuclear factor-kappaB and activator protein-1, which bind to and activate
      coactivator molecules that acetylate core histones and switch on gene
      transcription. Corticosteroids suppress the multiple inflammatory genes that are
      activated in asthmatic airways, mainly by reversing histone acetylation of
      activated inflammatory genes through binding of glucocorticoid receptors to
      coactivators and recruitment of histone deacetylase 2 to the activated
      transcription complex. Activated glucocorticoid receptors also bind to
      recognition sites in the promoters of certain genes in order to activate their
      transcription, resulting in secretion of anti-inflammatory proteins, such as
      mitogen-activated protein kinase phosphatase-1, which inhibits mitogen-activated
      protein kinase signalling pathways. Glucocorticoid receptors may also interact
      with other recognition sites to inhibit transcription, for example of several
      genes linked to their side-effects. In some patients with steroid-resistant
      asthma, there are abnormalities in glucocorticoid receptor signalling pathways.
      In chronic obstructive pulmonary disease patients and asthmatic patients who
      smoke, histone deacetylase 2 is markedly impaired as a result of
      oxidative/nitrative stress, and so inflammation is resistant to the anti
      inflammatory effects of corticosteroids. The therapeutic implications of these
      new findings are discussed.

PMID- 16452601
TI  - Radiotherapy: a novel treatment for pneumothorax.
AB  - Pneumothorax is a relatively common condition that is usually managed either
      conservatively, by chest tube drainage or, if a refractory air leak persists,
      then with cardiothoracic intervention. However, there is a small group of
      patients with a persistent air leak in whom surgical intervention is felt to be
      inappropriate. This study looks at a novel management strategy in a patient
      presenting with this scenario. A male with underlying bullous lung disease
      presented with a right pneumothorax. Complete re-expansion was not achieved,
      despite chest tube drainage and suction. Cardiothoracic intervention was felt to
      be inappropriate and the air leak persisted despite prolonged conservative
      management. Ventilation scintigraphy was therefore used to localise the air leak
      prior to targeted radiotherapy in an attempt to seal the leak via radiation
      induced fibrosis. Three weeks after the first fraction of radiotherapy, the air
      leak ceased. In complex cases of pneumothorax with persistent air leak where
      cardiothoracic intervention is deemed inappropriate, identification of the air
      leak site and localised radiotherapy could be considered.

PMID- 16452602
TI  - A "respiratory" cause of abdominal pain.

PMID- 16452603
TI  - A theory explaining time trends in asthma prevalence.

PMID- 16452604
TI  - Combined pulmonary fibrosis and emphysema in patients exposed to agrochemical
      compounds.

PMID- 16452605
TI  - Nasogastric tube feeding is a cause of aspiration pneumonia in ventilated
      patients.

PMID- 16452606
TI  - Eradication of Pseudomonas aeruginosa in cystic fibrosis.

PMID- 16452609
TI  - Implications of utilizing a phonics-based reading curriculum with children who
      are deaf or hard of hearing.
AB  - Extensive literature has reiterated the reading difficulties of students who are
      deaf or hard of hearing. Building and expanding upon the work of B. J. Trezek and
      K. W. Malmgren, this study demonstrated that given 1 year of instruction from a
      phonics-based reading curriculum supplemented by Visual Phonics, kindergarten and
      first-grade students who were deaf or hard of hearing could demonstrate
      improvements in beginning reading skills as measured by standardized assessments
      of (a) word reading, (b) pseudoword decoding, and (c) reading comprehension.
      Furthermore, the acquisition of beginning reading skills did not appear to be
      related to degree of hearing loss. In this study, students with various degrees
      of hearing loss benefited equally well from this phonics-based reading curriculum
      supplemented by Visual Phonics.

PMID- 16452610
TI  - Cochlear implanted pupils in Scottish schools: 4-year school attainment data
      (2000-2004).
AB  - The Achievements of Deaf Pupils in Scotland (ADPS) project has been tracking the
      educational attainment of deaf pupils in Scotland's schools since 2000. At the
      time of writing, the database contains records for 1,752 deaf pupils (2000-2005).
      Here 4-year aggregate educational attainment data are reported for a subset of
      152 school-aged deaf pupils with cochlear implants notified to the ADPS database
      between June 2000 and June 2004. The data describe primary and secondary school
      results in reading, writing, and math for this subgroup, as well as placement and
      communication characteristics. The educational attainment of the group of deaf
      pupils with cochlear implants is clearly marked when the deaf pupil population is
      disaggregated for hearing loss, achieving comparatively higher average attainment
      in both 5-14 Curriculum National Tests (Mathematics in particular) and Standard
      Grades. Therefore the gap in performance relative to the national population data
      is reduced for those deaf pupils, although it still widens at higher levels of
      achievement for the National Tests. Although most pupils with cochlear implants
      are placed in the mainstream, there is no pattern of migration toward mainstream
      schools. Some deaf pupils with cochlear implants moved out of mainstream to other
      types of placement, and this has implications for health-economic cost-utility
      assessments of cochlear implantation that favor mainstream education by drawing
      upon the relative cost of different placement types. These findings suggest that
      the ADPS program of research can contribute school outcome data as valuable real
      life outcome measures in wider assessments of the benefit of cochlear implants to
      deaf children and deaf young people.

PMID- 16452608
TI  - Flat affect in schizophrenia: relation to emotion processing and neurocognitive
      measures.
AB  - Impaired emotional functioning in schizophrenia is a prominent clinical feature
      that manifests primarily as flat affect. Studies have examined the perception,
      experience, and expression of emotions in schizophrenia and reported normal
      ratings of experience but impaired affect identification. However, the relation
      between flat affect and performance on facial affect identification and cognitive
      tasks has not been systematically examined in relation to premorbid adjustment
      and clinical outcome. We report a prospective study of 63 patients with at least
      moderate severity of flat affect and 99 patients without flat affect, who were
      compared on functional domains, emotion processing tasks, and neurocognitive
      measures. Flat affect was more common in men and was associated with poorer
      premorbid adjustment, worse current quality of life, and worse outcome at 1-year
      follow-up. Patients overall performed more poorly on emotion processing tasks,
      one that required identification of happy and sad emotions and one that required
      differentiating among intensities within these emotions. They responded
      inaccurately yet faster than controls for the intensity differentiation task,
      suggesting a decomposition of the normal relation between accuracy and speed.
      Flat affect ratings, compared with other negative symptoms, uniquely predicted
      performance on emotion processing tasks. Patients with flat affect showed greater
      impairment in both emotion processing tasks, with the most pronounced impairment
      for the intensity differentiation task. However, the 2 patient groups did not
      differ in the neurocognitive profile except for verbal memory. We conclude that
      flat affect is an important clinical feature of schizophrenia that exacerbates
      the course of illness.

PMID- 16452611
TI  - Hearing dogs: a longitudinal study of social and psychological effects on deaf
      and hard-of-hearing recipients.
AB  - The organization Hearing Dogs for Deaf People provides assistance dogs that alert
      their deaf or hard-of-hearing recipients to key sounds, thus increasing their
      independence and also providing companionship. Fifty-one recipients took part in
      a longitudinal study to monitor the dogs' working performance over time and to
      examine the social and psychological effects of having a Hearing Dog. The Profile
      of Mood State (POMS) questionnaire and the General Health Questionnaire (GHQ)
      were used together with a Hearing Dog Questionnaire (HDQ) specifically developed
      for this study. There were a number of significant differences in measures of
      well-being between the period prior to placing the Hearing Dog and the period
      after placement, but there were no comparable differences during the year-long
      waiting period prior to placement of the dog. Recipients reported significant
      reductions in hearing-related problems such as response to environmental sounds;
      significant reductions in measures of tension, anxiety, and depression; and
      significant improvements in social involvement and independence. The longitudinal
      nature of this study supports evidence that these improvements persist for some
      time after the placement of a dog, with significant differences being reported,
      in many cases, up to 18 months after acquiring a dog.

PMID- 16452612
TI  - Mimicking the action of GroEL in molecular dynamics simulations: application to
      the refinement of protein structures.
AB  - Bacterial chaperonin, GroEL, together with its co-chaperonin, GroES, facilitates
      the folding of a variety of polypeptides. Experiments suggest that GroEL
      stimulates protein folding by multiple cycles of binding and release. Misfolded
      proteins first bind to an exposed hydrophobic surface on GroEL. GroES then
      encapsulates the substrate and triggers its release into the central cavity of
      the GroEL/ES complex for folding. In this work, we investigate the possibility to
      facilitate protein folding in molecular dynamics simulations by mimicking the
      effects of GroEL/ES namely, repeated binding and release, together with spatial
      confinement. During the binding stage, the (metastable) partially folded proteins
      are allowed to attach spontaneously to a hydrophobic surface within the
      simulation box. This destabilizes the structures, which are then transferred into
      a spatially confined cavity for folding. The approach has been tested by
      attempting to refine protein structural models generated using the ROSETTA
      procedure for ab initio structure prediction. Dramatic improvements in regard to
      the deviation of protein models from the corresponding experimental structures
      were observed. The results suggest that the primary effects of the GroEL/ES
      system can be mimicked in a simple coarse-grained manner and be used to
      facilitate protein folding in molecular dynamics simulations. Furthermore, the
      results support the assumption that the spatial confinement in GroEL/ES assists
      the folding of encapsulated proteins.

PMID- 16452613
TI  - A general model of G protein-coupled receptor sequences and its application to
      detect remote homologs.
AB  - G protein-coupled receptors (GPCRs) constitute a large superfamily involved in
      various types of signal transduction pathways triggered by hormones, odorants,
      peptides, proteins, and other types of ligands. The superfamily is so diverse
      that many members lack sequence similarity, although they all span the cell
      membrane seven times with an extracellular N and a cytosolic C terminus. We
      analyzed a divergent set of GPCRs and found distinct loop length patterns and
      differences in amino acid composition between cytosolic loops, extracellular
      loops, and membrane regions. We configured GPCRHMM, a hidden Markov model, to fit
      those features and trained it on a large dataset representing the entire
      superfamily. GPCRHMM was benchmarked to profile HMMs and generic transmembrane
      detectors on sets of known GPCRs and non-GPCRs. In a cross-validation procedure,
      profile HMMs produced an error rate nearly twice as high as GPCRHMM. In a
      sensitivity-selectivity test, GPCRHMM's sensitivity was about 15% higher than
      that of the best transmembrane predictors, at comparable false positive rates. We
      used GPCRHMM to search for novel members of the GPCR superfamily in five
      proteomes. All in all we detected 120 sequences that lacked annotation and are
      potentially novel GPCRs. Out of those 102 were found in Caenorhabditis elegans,
      four in human, and seven in mouse. Many predictions (65) belonged to Pfam domains
      of unknown function. GPCRHMM strongly rejected a family of arthropod-specific
      odorant receptors believed to be GPCRs. A detailed analysis showed that these
      sequences are indeed very different from other GPCRs. GPCRHMM is available at
      http://gpcrhmm.cgb.ki.se.

PMID- 16452614
TI  - The solution structure of the methylated form of the N-terminal 16-kDa domain of
      Escherichia coli Ada protein.
AB  - The N-terminal 16-kDa domain of Escherichia coli Ada protein (N-Ada16k) repairs
      DNA methyl phosphotriester lesions by an irreversible methyl transfer to its
      cysteine residue. Upon the methylation, the sequence-specific DNA binding
      affinity for the promoter region of the alkylation resistance genes is enhanced
      by 10(3)-fold. Then, it acts as a transcriptional regulator for the methylation
      damage. In this paper, we identified the methyl acceptor residue of N-Ada16k and
      determined the solution structure of the methylated form of N-Ada16k by using NMR
      and mass spectrometry. The results of a 13C-filtered 1H-13C HMBC experiment and
      MALDI-TOF MS and MS/MS experiments clearly showed that the methyl acceptor
      residue is Cys38. The solution structure revealed that it has two distinct
      subdomains connected by a flexible linker loop: the methyltransferase (MTase)
      subdomain with the zinc-thiolate center, and the helical subdomain with a helix
      turn-helix motif. Interestingly, there is no potential hydrogen bond donor around
      Cys38, whereas the other three cysteine residues coordinated to a zinc ion have
      potential donors. Hence, Cys38 could retain its inherent nucleophilicity and
      react with a methyl phosphotriester. Furthermore, the structure comparison shows
      that there is no indication of a remarkable conformational change occurring upon
      the methylation. This implies that the electrostatic repulsion between the
      negatively charged DNA and the zinc-thiolate center may avoid the contact between
      the MTase subdomain and the DNA in the nonmethylated form. Thus, after the Cys38
      methylation, the MTase subdomain can bind the cognate DNA because the negative
      charge of the zinc-thiolate center is reduced.

PMID- 16452615
TI  - Domain:domain interactions within Hop, the Hsp70/Hsp90 organizing protein, are
      required for protein stability and structure.
AB  - The major heat shock protein (Hsp) chaperones Hsp70 and Hsp90 both bind the co
      chaperone Hop (Hsp70/Hsp90 organizing protein), which coordinates Hsp actions in
      folding protein substrates. Hop contains three tetratricopeptide repeat (TPR)
      domains that have binding sites for the conserved EEVD C termini of Hsp70 and
      Hsp90. Crystallographic studies have shown that EEVD interacts with positively
      charged amino acids in Hop TPR-binding pockets (called carboxylate clamps), and
      point mutations of these carboxylate clamp positions can disrupt Hsp binding. In
      this report, we use circular dichroism to assess the effects of point mutations
      and Hsp70/Hsp90 peptide binding on Hop conformation. Our results show that Hop
      global conformation is destabilized by single point mutations in carboxylate
      clamp positions at pH 5, while the structure of individual TPR domains is
      unaffected. Binding of peptides corresponding to the C termini of Hsp70 and Hsp90
      alters the global conformation of wild-type Hop, whereas peptide binding does not
      alter conformation of individual TPR domains. These results provide biophysical
      evidence that Hop-binding pockets are directly involved with domain:domain
      interactions, both influencing Hop global conformation and Hsp binding, and
      contributing to proper coordination of Hsp70 and Hsp90 interactions with protein
      substrates.

PMID- 16452617
TI  - Site-specific labeling of proteins for single-molecule FRET by combining chemical
      and enzymatic modification.
AB  - An often limiting factor for studying protein folding by single-molecule
      fluorescence resonance energy transfer (FRET) is the ability to site-specifically
      introduce a photostable organic FRET donor (D) and a complementary acceptor (A)
      into a polypeptide chain. Using alternating-laser excitation and chymotrypsin
      inhibitor 2 as a model, we show that chemical labeling of a unique cysteine,
      followed by enzymatic modification of a reactive glutamine in an N-terminally
      appended substrate sequence recognition tag for transglutaminase (TGase) affords
      stoichiometrically D-/A-labeled protein suitable for single-molecule FRET
      experiments. Thermodynamic data indicate that neither the presence of the TGase
      tag nor D/A labeling perturbs protein stability. As the N terminus in proteins is
      typically solvent accessible, a TGase tag can (in principle) be appended to any
      protein of interest by genetic engineering. Two-step chemical/enzymatic labeling
      may thus represent a simple, low-cost, and widely available strategy for D/A
      labeling of proteins for FRET-based single-molecule protein folding studies, even
      for non-protein-experts laboratories.

PMID- 16452616
TI  - Octapeptide repeat insertions increase the rate of protease-resistant prion
      protein formation.
AB  - A central feature of transmissible spongiform encephalopathies (TSE or prion
      diseases) involves the conversion of a normal, protease-sensitive glycoprotein
      termed prion protein (PrP-sen) into a pro-tease-resistant form, termed PrP-res.
      The N terminus of PrP-sen has five copies of a repeating eight amino acid
      sequence (octapeptide repeat). The presence of one to nine extra copies of this
      motif is associated with a heritable form of Creutzfeld-Jakob disease (CJD) in
      humans. An increasing number of octapeptide repeats correlates with earlier CJD
      onset, suggesting that the rate at which PrP-sen misfolds into PrP-res may be
      influenced by these mutations. In order to determine if octapeptide repeat
      insertions influence the rate at which PrP-res is formed, we used a hamster PrP
      amyloid-forming peptide (residues 23-144) into which two to 10 extra octapeptide
      repeats were inserted. The spontaneous formation of protease-resistant PrP
      amyloid from these peptides was more rapid in response to an increased number of
      octapeptide repeats. Furthermore, experiments using full-length glycosylated
      hamster PrP-sen demonstrated that PrP-res formation also occurred more rapidly
      from PrP-sen molecules expressing 10 extra copies of the octapeptide repeat. The
      rate increase for PrP-res formation did not appear to be due to any influence of
      the octapeptide repeat region on PrP structure, but rather to more rapid binding
      between PrP molecules. Our data from both models support the hypothesis that
      extra octapeptide repeats in PrP increase the rate at which protease resistant
      PrP is formed which in turn may affect the rate of disease onset in familial
      forms of CJD.

PMID- 16452618
TI  - Methionine oxidation of monomeric lambda repressor: the denatured state ensemble
      under nondenaturing conditions.
AB  - Although poorly understood, the properties of the denatured state ensemble are
      critical to the thermodynamics and the kinetics of protein folding. The most
      relevant conformations to cellular protein folding are the ones populated under
      physiological conditions. To avoid the problem of low expression that is seen
      with unstable variants, we used methionine oxidation to destabilize monomeric
      lambda repressor and predominantly populate the denatured state under
      nondenaturing buffer conditions. The denatured ensemble populated under these
      conditions comprises conformations that are compact. Analytical
      ultracentrifugation sedimentation velocity experiments indicate a small increase
      in Stokes radius over that of the native state. A significant degree of alpha
      helical structure in these conformations is detected by far-UV circular
      dichroism, and some tertiary interactions are suggested by near-UV circular
      dichroism. The characteristics of the denatured state populated by methionine
      oxidation in nondenaturing buffer are very different from those found in chemical
      denaturant.

PMID- 16452619
TI  - Solution structure of PcFK1, a spider peptide active against Plasmodium
      falciparum.
AB  - Psalmopeotoxin I (PcFK1) is a 33-amino-acid residue peptide isolated from the
      venom of the tarantula Psalmopoeus cambridgei. It has been recently shown to
      possess strong antiplasmodial activity against the intra-erythrocyte stage of
      Plasmodium falciparum in vitro. Although the molecular target for PcFK1 is not
      yet determined, this peptide does not lyse erythrocytes, is not cytotoxic to
      nucleated mammalian cells, and does not inhibit neuromuscular function. We
      investigated the structural properties of PcFK1 to help understand the unique
      mechanism of action of this peptide and to enhance its utility as a lead compound
      for rational development of new antimalarial drugs. In this paper, we have
      determined the three-dimensional solution structure by (1)H two-dimensional NMR
      means of recombinant PcFK1, which is shown to belong to the ICK structural
      superfamily with structural determinants common to several neurotoxins acting as
      ion channels effectors.

PMID- 16452620
TI  - Fluorescence resonance energy transfer and molecular modeling studies on 4',6
      diamidino-2-phenylindole (DAPI) complexes with tubulin.
AB  - The goal of this work was to determine the binding properties and location of
      4',6-diamidino-2-phenylindole (DAPI) complexed with tubulin. Using fluorescence
      anisotropy, a dissociation constant of 5.2+/-0.4 microM for the DAPI-tubulin
      complex was determined, slightly lower than that for the tubulin S complex. The
      influence of the C-terminal region on the binding of DAPI to tubulin was also
      characterized. Using FRET experiments, and assuming a kappa2 value of 2/3,
      distances between Co2+ bound to its high-affinity binding site and the DAPI
      binding site and 2',3'-O-(trinitrophenyl)guanosine 5'-triphosphate bound to the
      exchangeable nucleotide and the DAPI-binding site were found to be 20+/-2 A and
      43+/-2 A, respectively. To locate potential DAPI-binding sites on tubulin, a
      molecular modeling study was carried out using the tubulin crystal structure and
      energy minimization calculations. The results from the FRET measurements were
      used to limit the possible location of DAPI in the tubulin structure. Several
      candidate binding sites were found and these are discussed in the context of the
      various properties of bound DAPI.

PMID- 16452621
TI  - Temperature-induced reversible conformational change in the first 100 residues of
      alpha-synuclein.
AB  - Natively disordered proteins are a growing class of anomalies to the structure
      function paradigm. The natively disordered protein alpha-synuclein is the primary
      component of Lewy bodies, the cellular hallmark of Parkinson's disease. We
      noticed a dramatic difference in dilute solution 1H-15N Heteronuclear Single
      Quantum Coherence (HSQC) spectra of wild-type alpha-synuclein and two disease
      related mutants (A30P and A53T), with spectra collected at 35 degrees C showing
      fewer cross-peaks than spectra acquired at 10 degrees C. Here, we show the change
      to be the result of a reversible conformational exchange linked to an increase in
      hydrodynamic radius and secondary structure as the temperature is raised.
      Combined with analytical ultracentrifugation data showing alpha-synuclein to be
      monomeric at both temperatures, we conclude that the poor quality of the 1H-15N
      HSQC spectra obtained at 35 degrees C is due to conformational fluctuations that
      occur on the proton chemical shift time scale. Using a truncated variant of alpha
      synuclein, we show the conformational exchange occurs in the first 100 amino
      acids of the protein. Our data illustrate a key difference between globular and
      natively disordered proteins. The properties of globular proteins change little
      with solution conditions until they denature cooperatively, but the properties of
      natively disordered proteins can vary dramatically with solution conditions.

PMID- 16452622
TI  - Role of Trp140 at subsite -6 on the maltohexaose production of maltohexaose
      producing amylase from alkalophilic Bacillus sp.707.
AB  - Maltohexaose-producing amylase (G6-amylase) from alkalophilic Bacillus sp.707
      predominantly produces maltohexaose (G6) in the yield of >30% of the total
      products from short-chain amylose (DP=17). Our previous crystallographic study
      showed that G6-amylase has nine subsites, from -6 to +3, and pointed out the
      importance of the indole moiety of Trp140 in G6 production. G6-amylase has very
      low levels of hydrolytic activities for oligosaccharides shorter than
      maltoheptaose. To elucidate the mechanism underlying G6 production, we determined
      the crystal structures of the G6-amylase complexes with G6 and maltopentaose
      (G5). In the active site of the G6-amylase/G5 complex, G5 is bound to subsites -6
      to -2, while G1 and G6 are found at subsites +2 and -7 to -2, respectively, in
      the G6-amylase/G6 complex. In both structures, the glucosyl residue located at
      subsite -6 is stacked to the indole moiety of Trp140 within a distance of 4A. The
      measurement of the activities of the mutant enzymes when Trp140 was replaced by
      leucine (W140L) or by tyrosine (W140Y) showed that the G6 production from short
      chain amylose by W140L is lower than that by W140Y or wild-type enzyme. The face
      to-face short contact between Trp140 and substrate sugars is suggested to
      regulate the disposition of the glucosyl residue at subsite -6 and to govern
      product specificity for G6 production.

PMID- 16452623
TI  - Global structural rearrangement of the cell penetrating ribonuclease colicin E3
      on interaction with phospholipid membranes.
AB  - Nuclease type colicins and related bacteriocins possess the unprecedented ability
      to translocate an enzymatic polypeptide chain across the Gram-negative cell
      envelope. Here we use the rRNase domain of the cytotoxic ribonuclease colicin E3
      to examine the structural changes on its interaction with the membrane. Using
      phospholipid vesicles as model membranes we show that anionic membranes
      destabilize the nuclease domain of the rRNase type colicin E3. Intrinsic
      tryptophan fluorescence and circular dichroism show that vesicles consisting of
      pure DOPA act as a powerful protein denaturant toward the rRNase domain, although
      this interaction can be entirely prevented by the addition of salt. Binding of E3
      rRNase to DOPA vesicles is an endothermic process (DeltaH=24 kcal mol-1),
      reflecting unfolding of the protein. Consistent with this, binding of a highly
      destabilized mutant of the E3 rRNase to DOPA vesicles is exothermic. With mixed
      vesicles containing anionic and neutral phospholipids at a ratio of 1:3, set to
      mimic the charge of the Escherichia coli inner membrane, destabilization of E3
      rRNase is lessened, although the melting temperature of the protein at pH 7.0 is
      greatly reduced from 50 degrees C to 30 degrees C. The interaction of E3 rRNase
      with 1:3 DOPA:DOPC vesicles is also highly dependent on both ionic strength and
      temperature. We discuss these results in terms of the likely interaction of the
      E3 rRNase and the related E9 DNase domains with the E. coli inner membrane and
      their subsequent translocation to the cell cytoplasm.

PMID- 16452625
TI  - Exploring the interaction between the protein kinase A catalytic subunit and
      caveolin-1 scaffolding domain with shotgun scanning, oligomer complementation,
      NMR, and docking.
AB  - The techniques of phage-displayed homolog shotgun scanning, oligomer
      complementation, NMR secondary structure analysis, and computational docking
      provide a complementary suite of tools for dissecting protein-protein
      interactions. Focusing these tools on the interaction between the catalytic sub
      unit of protein kinase A (PKAcat) and caveolin-1 scaffolding domain (CSD) reveals
      the first structural model for the interaction. Homolog shotgun scanning varied
      each CSD residue as either a wild-type or a homologous amino acid. Wild-type to
      homolog ratios from 116 different homologous CSD variants identified side-chain
      functional groups responsible for precise contacts with PKAcat. Structural
      analysis by NMR assigned an alpha-helical conformation to the central residues 84
      97 of CSD. The extensive mutagenesis data and NMR secondary structure
      information provided constraints for developing a model for the PKAcat-CSD
      interaction. Addition of synthetic CSD to phage-displayed CSD resulted in
      oligomer complementation, or enhanced binding to PKAcat. Together with previous
      experiments examining the interaction between CSD and endothelial nitric oxide
      synthase (eNOS), the results suggest a general oligomerization-dependent
      enhancement of binding between signal transducing enzymes and caveolin-1.

PMID- 16452624
TI  - Genetic selection for protein solubility enabled by the folding quality control
      feature of the twin-arginine translocation pathway.
AB  - One of the most vexing problems facing structural genomics efforts and the
      biotechnology enterprise in general is the inability to efficiently produce
      functional proteins due to poor folding and insolubility. Additionally, protein
      misfolding and aggregation has been linked to a number of human diseases, such as
      Alzheimer's. Thus, a robust cellular assay that allows for direct monitoring,
      manipulation, and improvement of protein folding could have a profound impact. We
      report the development and characterization of a genetic selection for protein
      folding and solubility in living bacterial cells. The basis for this assay is the
      observation that protein transport through the bacterial twin-arginine
      translocation (Tat) pathway depends on correct folding of the protein prior to
      transport. In this system, a test protein is expressed as a tripartite fusion
      between an N-terminal Tat signal peptide and a C-terminal TEM1 beta-lactamase
      reporter protein. We demonstrate that survival of Escherichia coli cells on
      selective medium expressing a Tat-targeted test protein/beta-lactamase fusion
      correlates with the solubility of the test protein. Using this assay, we isolated
      solubility-enhanced variants of the Alzheimer's Abeta42 peptide from a large
      combinatorial library of Abeta42 sequences, thereby confirming that our assay is
      a highly effective selection tool for soluble proteins. By allowing the bacterial
      Tat pathway to exert folding quality control on expressed target protein
      sequences, we have generated a powerful tool for monitoring protein folding and
      solubility in living cells, for molecular engineering of solubility-enhanced
      proteins or for the isolation of factors and/or cellular conditions that
      stabilize aggregation-prone proteins.

PMID- 16452626
TI  - Monitoring protein aggregation during thermal unfolding in circular dichroism
      experiments.
AB  - Thermal unfolding monitored by spectroscopy or calorimetry is widely used to
      determine protein stability. Equilibrium thermodynamic analysis of such unfolding
      is often hampered by its irreversibility, which usually results from aggregation
      of thermally denatured protein. In addition, heat-induced protein misfolding and
      aggregation often lead to formation of amyloid-like structures. We propose a
      convenient method to monitor in real time protein aggregation during thermal
      folding/ unfolding transition by recording turbidity or 90 degrees light
      scattering data in circular dichroism (CD) spectroscopic experiments. Since the
      measurements of turbidity and 90 degrees light scattering can be done
      simultaneously with far- or near-UV CD data collection, they require no
      additional time or sample and can be directly correlated with the protein
      conformational changes monitored by CD. The results can provide useful insights
      into the origins of irreversible conformational changes and test the linkage
      between protein unfolding or misfolding and aggregation in various macromolecular
      systems, including globular proteins and protein-lipid complexes described in
      this study, as well as a wide range of amyloid-forming proteins and peptides.

PMID- 16452627
TI  - Cooperative hydrogen bond interactions in the streptavidin-biotin system.
AB  - The thermodynamic and structural cooperativity between the Ser45- and D128-biotin
      hydrogen bonds was measured by calorimetric and X-ray crystallographic studies of
      the S45A/D128A double mutant of streptavidin. The double mutant exhibits a
      binding affinity approximately 2x10(7) times lower than that of wild-type
      streptavidin at 25 degrees C. The corresponding reduction in binding free energy
      (DeltaDeltaG) of 10.1 kcal/mol was nearly completely due to binding enthalpy
      losses at this temperature. The loss of binding affinity is 11-fold greater than
      that predicted by a linear combination of the single-mutant energetic
      perturbations (8.7 kcal/mol), indicating that these two mutations interact
      cooperatively. Crystallographic characterization of the double mutant and
      comparison with the two single mutant structures suggest that structural
      rearrangements at the S45 position, when the D128 carboxylate is removed, mask
      the true energetic contribution of the D128-biotin interaction. Taken together,
      the thermodynamic and structural analyses support the conclusion that the wild
      type hydrogen bond between D128-OD and biotin-N2 is thermodynamically stronger
      than that between S45-OG and biotin-N1.

PMID- 16452628
TI  - Differential requirements for actin polymerization, calmodulin, and Ca2+ define
      distinct stages of lysosome/phagosome targeting.
AB  - Fusion of phagosomes with late endocytic organelles is essential for cellular
      digestion of microbial pathogens, senescent cells, apoptotic bodies, and retinal
      outer segment fragments. To further elucidate the biochemistry of the targeting
      process, we developed a scintillation proximity assay to study the stepwise
      association of lysosomes and phagosomes in vitro. Incubation of tritium-labeled
      lysosomes with phagosomes containing scintillant latex beads led to light
      emission in a reaction requiring cytosol, ATP, and low Ca(2+) concentrations. The
      nascent complex was sensitive to disruption by alkaline carbonate, indicating
      that the organelles had "docked" but not fused. Through inhibitor studies and
      fluorescence microscopy we show that docking is preceded by a tethering step that
      requires actin polymerization and calmodulin. In the docked state ongoing actin
      polymerization and calmodulin are no longer necessary. The tethering/docking
      activity was purified to near homogeneity from rat liver cytosol. Major proteins
      in the active fractions included actin, calmodulin and IQGAP2. IQGAPs are known
      to bind calmodulin and cross-link F-actin, suggesting a key coordinating role
      during lysosome/phagosome attachment. The current results support the conclusion
      that lysosome/phagosome interactions proceed through distinct stages and provide
      a useful new approach for further experimental dissection.

PMID- 16452629
TI  - Domains within the GARP subunit Vps54 confer separate functions in complex
      assembly and early endosome recognition.
AB  - Tethering complexes contribute to the specificity of membrane fusion by
      recognizing organelle features on both donor and acceptor membranes. The Golgi
      associated retrograde protein (GARP) complex is required for retrograde traffic
      from both early and late endosomes to the trans-Golgi network (TGN), presenting a
      paradox as to how a single complex can interact specifically with vesicles from
      multiple upstream compartments. We have found that a subunit of the GARP complex,
      Vps54, can be separated into N- and C-terminal regions that have different
      functions. Whereas the N-terminus of Vps54 is important for GARP complex assembly
      and stability, a conserved C-terminal domain mediates localization to an early
      endocytic compartment. Mutation of this C-terminal domain has no effect on
      retrograde transport from late endosomes. However, a specific defect in retrieval
      of Snc1 from early endosomes is observed when recycling from late endosomes to
      the Golgi is blocked. These data suggest that separate domains recruit tethering
      complexes to different upstream compartments to regulate individual trafficking
      pathways.

PMID- 16452630
TI  - EDEM is involved in retrotranslocation of ricin from the endoplasmic reticulum to
      the cytosol.
AB  - The plant toxin ricin is transported retrogradely from the cell surface to the
      endoplasmic reticulum (ER) from where the enzymatically active part is
      retrotranslocated to the cytosol, presumably by the same mechanism as used by
      misfolded proteins. The ER degradation enhancing alpha-mannosidase I-like
      protein, EDEM, is responsible for directing aberrant proteins for ER-associated
      protein degradation. In this study, we have investigated whether EDEM is involved
      in ricin retrotranslocation. Overexpression of EDEM strongly protects against
      ricin. However, when the interaction between EDEM and misfolded proteins is
      inhibited by kifunensin, EDEM promotes retrotranslocation of ricin from the ER to
      the cytosol. Furthermore, puromycin, which inhibits synthesis and thereby
      transport of proteins into the ER, counteracted the protection seen in EDEM
      transfected cells. Coimmunoprecipitation studies revealed that ricin can interact
      with EDEM and with Sec61alpha, and both kifunensin and puromycin increase these
      interactions. Importantly, vector-based RNA interference against EDEM, which
      leads to reduction of the cellular level of EDEM, decreased retrotranslocation of
      ricin A-chain to the cytosol. In conclusion, our results indicate that EDEM is
      involved in retrotranslocation of ricin from the ER to the cytosol.

PMID- 16452631
TI  - Versican mediates mesenchymal-epithelial transition.
AB  - Versican is a large extracellular chondroitin sulfate proteoglycan that belongs
      to the family of lecticans. Alternative splicing of versican generates at least
      four isoforms named V0, V1, V2, and V3. We show here that ectopic expression of
      versican V1 isoform induced mesenchymal-epithelial transition (MET) in NIH3T3
      fibroblasts, and inhibition of endogenous versican expression abolished the MET
      in metanephric mesenchyme. MET in NIH3T3 cells was demonstrated by morphological
      changes and dramatic alterations in both membrane and cytoskeleton architecture.
      Molecular analysis showed that V1 promoted a "switch" in cadherin expression from
      N- to E-cadherin, resulting in epithelial specific adhesion junctions. V1
      expression reduced vimentin levels and induced expression of occludin, an
      epithelial-specific marker, resulting in polarization of V1-transfected cells.
      Furthermore, an MSP (methylation-specific PCR) assay showed that N-cadherin
      expression was suppressed through methylation of its DNA promoter. Exogenous
      expression of N-cadherin in V1-transfected cells reversed V1's effect on cell
      aggregation. Reduction of E-cadherin expression by Snail transfection and siRNA
      targeting E-cadherin abolished V1-induced morphological alteration. Transfection
      of an siRNA construct targeting versican also reversed the changed morphology
      induced by V1 expression. Silencing of endogenous versican prevented MET of
      metanephric mesenchyme. Taken together, our results demonstrate the involvement
      of versican in MET: expression of versican is sufficient to induce MET in NIH3T3
      fibroblasts and reduction of versican expression decreased MET in metanephric
      mesenchyme.

PMID- 16452632
TI  - Loss of P4 ATPases Drs2p and Dnf3p disrupts aminophospholipid transport and
      asymmetry in yeast post-Golgi secretory vesicles.
AB  - Eukaryotic plasma membranes generally display asymmetric lipid distributions with
      the aminophospholipids concentrated in the cytosolic leaflet. This arrangement is
      maintained by aminophospholipid translocases (APLTs) that use ATP hydrolysis to
      flip phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the external
      to the cytosolic leaflet. The identity of APLTs has not been established, but
      prime candidates are members of the P4 subfamily of P-type ATPases. Removal of P4
      ATPases Dnf1p and Dnf2p from budding yeast abolishes inward translocation of 6
      [(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminocaproyl] (NBD)-labeled PS, PE, and
      phosphatidylcholine (PC) across the plasma membrane and causes cell surface
      exposure of endogenous PE. Here, we show that yeast post-Golgi secretory vesicles
      (SVs) contain a translocase activity that flips NBD-PS, NBD-PE, and NBD-PC to the
      cytosolic leaflet. This activity is independent of Dnf1p and Dnf2p but requires
      two other P4 ATPases, Drs2p and Dnf3p, that reside primarily in the trans-Golgi
      network. Moreover, SVs have an asymmetric PE arrangement that is lost upon
      removal of Drs2p and Dnf3p. Our results indicate that aminophospholipid asymmetry
      is created when membrane flows through the Golgi and that P4-ATPases are
      essential for this process.

PMID- 16452633
TI  - The Gcs1 Arf-GAP mediates Snc1,2 v-SNARE retrieval to the Golgi in yeast.
AB  - Gcs1 is an Arf GTPase-activating protein (Arf-GAP) that mediates Golgi-ER and
      post-Golgi vesicle transport in yeast. Here we show that the Snc1,2 v-SNAREs,
      which mediate endocytosis and exocytosis, interact physically and genetically
      with Gcs1. Moreover, Gcs1 and the Snc v-SNAREs colocalize to subcellular
      structures that correspond to the trans-Golgi and endosomal compartments. Studies
      performed in vitro demonstrate that the Snc-Gcs1 interaction results in the
      efficient binding of recombinant Arf1Delta17N-Q71L to the v-SNARE and the
      recruitment of purified coatomer. In contrast, the presence of Snc had no effect
      on Gcs1 Arf-GAP activity in vitro, suggesting that v-SNARE binding does not
      attenuate Arf1 function. Disruption of both the SNC and GCS1 genes results in
      synthetic lethality, whereas overexpression of either SNC gene inhibits the
      growth of a distinct subset of COPI mutants. We show that GFP-Snc1 recycling to
      the trans-Golgi is impaired in gcs1Delta cells and these COPI mutants. Together,
      these results suggest that Gcs1 facilitates the incorporation of the Snc v-SNAREs
      into COPI recycling vesicles and subsequent endosome-Golgi sorting in yeast.

PMID- 16452634
TI  - GSK-3 is activated by the tyrosine kinase Pyk2 during LPA1-mediated neurite
      retraction.
AB  - Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine kinase
      that is usually inactivated by serine phosphorylation in response to
      extracellular cues. However, GSK-3 can also be activated by tyrosine
      phosphorylation, but little is known about the upstream signaling events and
      tyrosine kinase(s) involved. Here we describe a G protein signaling pathway
      leading to GSK-3 activation during lysophosphatidic acid (LPA)-induced neurite
      retraction. Using neuronal cells expressing the LPA(1) receptor, we show that
      LPA(1) mediates tyrosine phosphorylation and activation of GSK-3 with subsequent
      phosphorylation of the microtubule-associated protein tau via the G(i)-linked
      PIP(2) hydrolysis-Ca(2+) mobilization pathway. LPA concomitantly activates the
      Ca(2+)-dependent tyrosine kinase Pyk2, which is detected in a complex with GSK
      3beta. Inactivation or knockdown of Pyk2 inhibits LPA-induced (but not basal)
      tyrosine phosphorylation of GSK-3 and partially inhibits LPA-induced neurite
      retraction, similar to what is observed following GSK-3 inhibition. Thus, Pyk2
      mediates LPA(1)-induced activation of GSK-3 and subsequent phosphorylation of
      microtubule-associated proteins. Pyk2-mediated GSK-3 activation is initiated by
      PIP(2) hydrolysis and may serve to destabilize microtubules during actomyosin
      driven neurite retraction.

PMID- 16452635
TI  - Involvement of mitochondrial complex II defects in neuronal death produced by N
      terminus fragment of mutated huntingtin.
AB  - Alterations of mitochondrial function may play a central role in neuronal death
      in Huntington's disease (HD). However, the molecular mechanisms underlying such
      functional deficits of mitochondria are not elucidated yet. We herein showed that
      the expression of two important constituents of mitochondrial complex II, the 30
      kDa iron-sulfur (Ip) subunit and the 70-kDa FAD (Fp) subunit, was preferentially
      decreased in the striatum of HD patients compared with controls. We also examined
      several mitochondrial proteins in striatal neurons that were infected with
      lentiviral vectors coding for the N-terminus part of huntingtin (Htt) with either
      a pathological (Htt171-82Q) or physiological (Htt171-19Q) polyglutamine tract.
      Compared with Htt171-19Q, expression of Htt171-82Q preferentially decreased the
      levels of Ip and Fp subunits and affected the dehydrogenase activity of the
      complex. The Htt171-82Q-induced preferential loss of complex II was not
      associated with a decrease in mRNA levels, suggesting the involvement of a
      posttranscriptional mechanism. Importantly, the overexpression of either Ip or Fp
      subunit restored complex II levels and blocked mitochondrial dysfunction and
      striatal cell death induced by Htt171-82Q in striatal neurons. The present
      results strongly suggest that complex II defects in HD may be instrumental in
      striatal cell death.

PMID- 16452637
TI  - Cholesterol is required for efficient endoplasmic reticulum-to-Golgi transport of
      secretory membrane proteins.
AB  - Although cholesterol is synthesized in the endoplasmic reticulum (ER), compared
      with other cellular membranes, ER membrane has low cholesterol (3-6%). Most of
      the molecular machinery that regulates cellular cholesterol homeostasis also
      resides in the ER. Little is known about how cholesterol itself affects the ER
      membrane. Here, we demonstrate that acute cholesterol depletion in ER membranes
      impairs ER-to-Golgi transport of secretory membrane proteins. Cholesterol
      depletion is achieved by a brief inhibition of cholesterol synthesis with statins
      in cells grown in cholesterol-depleted medium. We provide evidence that secretory
      membrane proteins vesicular stomatitis virus glycoprotein and scavenger receptor
      A failed to be efficiently transported from the ER upon cholesterol depletion.
      Fluorescence photobleaching recovery experiments indicated that cholesterol
      depletion by statins leads to a severe loss of lateral mobility on the ER
      membrane of these transmembrane proteins, but not loss of mobility of proteins in
      the ER lumen. This impaired lateral mobility is correlated with impaired ER-to
      Golgi transport. These results provide evidence for the first time that
      cholesterol is required in the ER membrane to maintain mobility of membrane
      proteins and thus protein secretion.

PMID- 16452638
TI  - GABA-A receptors regulate neocortical neuronal migration in vitro and in vivo.
AB  - The cortical migration process depends on a number of trophic factors and on the
      activation of different voltage- and ligand-gated channels. We investigated the
      role of gamma-aminobutyric acid (GABA) type A receptors in the neuronal migration
      process of the newborn rat parietal cortex in vivo and in vitro. Local in vivo
      application of the GABA-A antagonist bicuculline methiodide (BMI) or the agonist
      muscimol via cortical surface Elvax implants induced prominent alterations in the
      cortical architecture when compared with untreated or sham-operated controls. BMI
      and muscimol-treated animals revealed heterotopic cell clusters in the upper
      layers and a complete loss of the cortical lamination in the region underlying
      the Elvax implant. Immunocytochemical staining for glial fibrillary acidic
      protein, N-methyl-D-aspartate receptors, and GABA demonstrated that heterotopia
      was not provoked by glial proliferation and confirmed the presence of both
      glutamatergic and GABAergic neurons. In organotypic neocortical slices from
      embryonic day 18-19 embryos, application of BMI and to a lesser extent also
      muscimol induced an increase in the migration speed and an accumulation of
      neurons in the upper cortical layers. Spontaneous intracellular calcium ([Ca2+]i)
      oscillations in neocortical slices from newborn rats were abolished by BMI (5 and
      20 microM) and muscimol (1 and 10 microM), indicating that both compounds
      interfere with [Ca2+]i signaling required for normal neuronal migration.
      Electrophysiological recordings from migrating neurons in newborn rat neocortical
      slices indicate that long-term application of muscimol causes a pronounced
      reduction (1 microM muscimol) or blockade (10 microM) in the responsiveness of
      postsynaptic GABA-A receptors due to a pronounced receptor desensitization. Our
      results indicate that modulation of GABA-A receptors by compounds acting as
      agonists or antagonists may profoundly influence the neuronal migration process
      in the developing cerebral cortex.

PMID- 16452636
TI  - Cell surface transglutaminase promotes RhoA activation via integrin clustering
      and suppression of the Src-p190RhoGAP signaling pathway.
AB  - Tissue transglutaminase (tTG) is a multifunctional protein that serves as cross
      linking enzyme and integrin-binding adhesion coreceptor for fibronectin on the
      cell surface. Previous work showed activation of small GTPase RhoA via enzymatic
      transamidation by cytoplasmic tTG. Here, we report an alternative nonenzymatic
      mechanism of RhoA activation by cell surface tTG. Direct engagement of surface
      tTG with specific antibody or the fibronectin fragment containing modules
      I(6)II(1,2)I(7-9) increases RhoA-GTP levels. Integrin-dependent signaling to RhoA
      and its downstream target Rho-associated coiled-coil containing serine/threonine
      protein kinase (ROCK) is amplified by surface tTG. tTG expression on the cell
      surface elevates RhoA-GTP levels in nonadherent and adherent cells, delays
      maximal RhoA activation upon cell adhesion to fibronectin and accelerates a rise
      in RhoA activity after binding soluble integrin ligands. These data indicate that
      surface tTG induces integrin clustering regardless of integrin-ligand
      interactions. This notion is supported by visualization of integrin clusters,
      increased susceptibility of integrins to chemical cross-linking, and biochemical
      detection of large integrin complexes in cells expressing tTG. In turn, integrin
      aggregation by surface tTG inhibits Src kinase activity and decreases activation
      of the Src substrate p190RhoGAP. Moreover, pharmacological inhibition of Src
      kinase reveals inactivation of Src signaling as the primary cause of elevated
      RhoA activity in cells expressing tTG. Together, these findings show that surface
      tTG amplifies integrin-mediated signaling to RhoA/ROCK via integrin clustering
      and down-regulation of the Src-p190RhoGAP regulatory pathway.

PMID- 16452640
TI  - Alpha phase reset contributes to the generation of ERPs.
AB  - An unresolved question in electroencephalogram (EEG) research is whether event
      related potentials (ERPs) are generated by phase-reset or evoked response. We
      analyzed data of a visual feature detection task and will show 1) phase
      concentration in the alpha frequency range, 2) ongoing alpha activity prior to
      stimulus onset, 3) evoked alpha oscillation in the ERP, 4) lack of power increase
      during phase concentration, 5) decrease in amplitude variance during early evoked
      components preceding a decrease in power, and 6) the same cortical sources for
      induced prestimulus power and evoked poststimulus power. Because none of these
      data provide unequivocal evidence for phase reset, we additionally tested the
      basic assumption of the evoked model, which is the additivity of the evoked
      response on the basis of a simulation approach. Our findings suggest that
      nonadditive processes-typical for a phase reset-are involved in the generation of
      the ERP. Thus, together with the other findings this study provides unequivocal
      evidence for phase resetting in the human EEG.

PMID- 16452639
TI  - A temporal continuity to the vertical organization of the human neocortex.
AB  - Radial translaminar arrays of pyramidal cells-minicolumns-are a pervasive
      structural motif of placental mammalian neocortex, which are anticipated in the
      earliest stages of cortical development by the formation of ontogenetic cell
      columns comprising radial glial cells and associated radially migrating neurons.
      In the present study we examine the temporal continuity in these structures
      throughout development and aging. Computerized image analysis of micrograph Nissl
      stained postmortem tissue produced estimates of the median free path through
      neuropil in the radial direction (parallel to pyramidal cell arrays) and in the
      tangential direction (parallel to the cortical surface). These data were modeled
      as a biphasic power law with respect to in utero development and postnatal age,
      multiplied by a decay factor. No significant change in the ratio of radial to
      tangential neuropil space was demonstrated in either the prenatal or postnatal
      sample population. Neuropil development follows a prenatal phase of cubic
      volumetric growth with a postnatal phase of linear volumetric growth. The data
      suggest the continuity of columnar structures from early in gestation through
      postnatal maturation.

PMID- 16452641
TI  - Impairment and facilitation of transverse patterning after lesions of the
      perirhinal cortex and hippocampus, respectively.
AB  - We have recently suggested that certain effects of perirhinal cortex removals in
      monkeys can be attributed to the lesion compromising complex configural
      representations of visual stimuli. On this view, monkeys with perirhinal cortex
      lesions will be impaired on acquisition of discrimination problems that possess
      high "feature ambiguity," that is, those in which many of the same features
      belong to both rewarded and unrewarded stimuli. A subclass of feature-ambiguous
      problems includes "configural" discrimination problems in which all features are
      ambiguous. In the present study, we tested control monkeys and monkeys with
      bilateral lesions of perirhinal cortex on a configural discrimination problem,
      the transverse-patterning task (i.e., A+ vs. B-, B+ vs. C-, C+ vs. A-), using
      complex 2-dimensional visual stimuli. In addition, we investigated the effects of
      lesions to another structure that has been implicated in configural learning, the
      hippocampus. Monkeys with perirhinal cortex lesions were impaired, whereas
      monkeys with selective hippocampal lesions were facilitated, on acquisition of
      the transverse-patterning task. These data do not provide support for mass action
      theories of medial temporal lobe function, which cannot account for the opposing
      effects of the 2 lesions. These results are, however, compatible with a view that
      perirhinal cortex, and not the hippocampus, contains complex configural
      representations of visual stimuli critical to the solution of the transverse
      patterning task.

PMID- 16452642
TI  - Small-world networks and functional connectivity in Alzheimer's disease.
AB  - We investigated whether functional brain networks are abnormally organized in
      Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to
      matrices of functional connectivity of beta band-filtered electroencephalography
      (EEG) channels, in 15 Alzheimer patients and 13 control subjects. Correlations
      between all pairwise combinations of EEG channels were determined with the
      synchronization likelihood. The resulting synchronization matrices were converted
      to graphs by applying a threshold, and cluster coefficients and path lengths were
      computed as a function of threshold or as a function of degree K. For a wide
      range of thresholds, the characteristic path length L was significantly longer in
      the Alzheimer patients, whereas the cluster coefficient C showed no significant
      changes. This pattern was still present when L and C were computed as a function
      of K. A longer path length with a relatively preserved cluster coefficient
      suggests a loss of complexity and a less optimal organization. The present study
      provides further support for the presence of "small-world" features in functional
      brain networks and demonstrates that AD is characterized by a loss of small-world
      network characteristics. Graph theoretical analysis may be a useful approach to
      study the complexity of patterns of interrelations between EEG channels.

PMID- 16452643
TI  - Large-scale visuomotor integration in the cerebral cortex.
AB  - Efficient visuomotor behavior depends on integrated processing by the visual and
      motor systems of the cerebral cortex. Yet, many previous cortical neurophysiology
      studies have examined the visual and motor modalities in isolation, largely
      ignoring questions of large-scale cross-modal integration. To address this issue,
      we analyzed event-related local field potentials simultaneously recorded from
      multiple visual, motor, and executive cortical sites in monkeys performing a
      visuomotor pattern discrimination task. The timing and cortical location of four
      aspects of event-related activities were examined: stimulus-evoked activation
      onset, stimulus-specific processing, stimulus category-specific processing, and
      response-specific processing. Activations appeared earliest in striate cortex and
      rapidly thereafter in other visual areas. Stimulus-specific processing began
      early in most visual cortical areas, some at activation onset. Early onset
      latencies were also observed in motor, premotor, and prefrontal areas, some as
      early as in striate cortex, but these early-activating frontal sites did not show
      early stimulus-specific processing. Response-specific processing began around 150
      ms poststimulus in widespread cortical areas, suggesting that perceptual decision
      formation and response selection arose through concurrent processes of visual,
      motor, and executive areas. The occurrence of stimulus-specific and stimulus
      category-specific differences after the onset of response-specific processing
      suggests that sensory and motor stages of visuomotor processing overlapped in
      time.

PMID- 16452644
TI  - Manganese-enhanced MRI reveals structural and functional changes in the cortex of
      Bassoon mutant mice.
AB  - Manganese-enhanced magnetic resonance imaging (ME-MRI) was used to analyze the
      brain architecture in mice lacking the functional presynaptic active zone protein
      Bassoon. Anatomical characterization revealed a significant increase in the total
      brain volume in Bassoon mutants as compared with wild-type mice, which is mainly
      caused by changes in cortex and hippocampus volume. The measured enlargement in
      cortical volume coincides with an altered Mn2+ distribution within cortical
      layers as visualized by T1-weighted magnetic resonance imaging. Two days after
      manganese application, the cortex of Bassoon mutant mice appeared more laminated
      in ME-MRI, with an enhanced accumulation of manganese in deep, central, and
      superficial cortical cell layers. Whereas morphologically the cortical lamination
      is not affected by the absence of a functional Bassoon, an altered basal
      activation pattern was found in the cortex of the mutant mice both by metabolic
      labeling with [14C]-2-deoxyglucose and histochemical detection of the potassium
      analogue thallium uptake. Consequently, the results indicate that the absence of
      the functional presynaptic protein Bassoon causes disturbance in the formation of
      normal basal cortical activation patterns and thereby in the functional cortical
      architecture. Furthermore, this study shows that ME-MRI can become a valuable
      tool for a structural characterization of genetically modified mice.

PMID- 16452645
TI  - An exploration of social cognitive theory mediators of father-son communication
      about sex.
AB  - OBJECTIVES: R.E.A.L. MEN (responsible, empowered, aware, living) is an HIV
      prevention project developed for fathers and their sons. The primary aim of
      R.E.A.L. MEN was to test the efficacy of an intervention to promote delay of
      sexual intercourse among 11- to 14-year-old adolescents and to enhance the
      father's role as a sexuality educator. In this article, we report the outcomes
      related to father-son communication about sex and the results of an exploratory
      analysis to test the hypothesis that the intervention effect on father-son
      communication about sex-related topics is mediated by the social cognitive
      variables of self-efficacy and outcome expectations. METHODS: Two hundred seventy
      seven fathers and their sons enrolled in the study. Fathers randomized to the
      intervention group attended seven group sessions, and their sons attended the
      final session with them. Fathers and sons completed baseline and 3-, 6-, and 12
      month follow-up assessments. The fathers who completed the 3-month follow-up
      assessment were included in the mediation analyses described in this article.
      RESULTS: All the participants were male, most were African American (97%), and
      most fathers and sons reported residing in the same household. The mean age of
      father participants was 40.5 years; most had graduated from high school, and
      about 60% reported a yearly income over 30,000 dollars. Based on the results of
      mediation analyses, the data supported a mediation model that suggests that the
      effect of the intervention on father-son communication was mediated by
      differences in self-efficacy. A mediation effect for outcome expectations was
      weak and could not be validated using additional tests. CONCLUSIONS: The
      mediation analysis provides some understanding of the role of self-efficacy and
      outcome expectations in promoting behavioral change. Understanding the active
      components of interventions can help refine the interventions to eliminate
      nonfunctioning components and enhance the active components leading to more
      streamlined programs.

PMID- 16452646
TI  - Community collaborative youth-focused HIV/AIDS prevention in South Africa and
      Trinidad: preliminary findings.
AB  - BACKGROUND: South Africa and Trinidad and Tobago are disproportionately impacted
      by high rates of HIV/AIDS among adolescents. OBJECTIVE: The article describes the
      HIV crises in these countries; outlines a community participatory research
      framework to adapt and deliver family-based prevention; and presents preliminary
      data from intervention pilots in each setting. METHODS: Adapted interventions
      were piloted with N = 140 families in South Africa and N=16 families in Trinidad
      and Tobago to refine recruitment and retention efforts and to assess the adapted
      interventions' impact on family and risk-related constructs. RESULTS: Both
      settings reported promising results including high recruitment and retention and
      favourable pre to post changes in parent/youth frequency and comfort in talking
      about sensitive subjects, HIV transmission knowledge and attitudes about persons
      with HIV/AIDS. CONCLUSION: International HIV-prevention alliances are increasing.
      Such alliances are challenged by trust issues, power-differentials and
      ideological differences. Recommendations are provided on how some challenges can
      be overcome.

PMID- 16452647
TI  - Hugging my uncle: the impact of a parent training on children's comfort
      interacting with persons living with HIV.
AB  - OBJECTIVE: HIV-related stigma affects not only persons living with HIV (PLwHIV)
      but also their communities and families including children. This study aimed to
      determine whether an interactive training administered to community parents
      significantly increases their children's reported comfort interacting with
      PLwHIV. METHODS: A randomized clinical trial with random-quota dwelling unit
      sampling and a random invitation to treatment had 238 parent and 238 child
      participants. RESULTS: For children of trained parents, significant increases in
      comfort were obtained, baseline to 6-month follow-up, on 14 of 22 reported daily
      activities with PLwHIV. For children who recently interacted with a person living
      with HIV, this comfort predicted the number of recent activities, even after
      controlling for closeness to the person living with HIV and for the number of
      persons with HIV known, living or deceased. CONCLUSIONS: Training parents to be
      HIV health educators of their children significantly impacts youth and shows
      promise for reducing HIV-related stigma and social isolation.

PMID- 16452648
TI  - Anisomycin and the reconsolidation hypothesis.

PMID- 16452649
TI  - Reduced extinction of hippocampal-dependent memories in CPEB knockout mice.
AB  - CPEB is a sequence-specific RNA binding protein that regulates translation at
      synapses. In neurons of CPEB knockout mice, synaptic efficacy is reduced. Here,
      we have performed a battery of behavioral tests and find that relative to wild
      type animals, CPEB knockout mice, although similar on many baseline behaviors,
      have reduced extinction of memories on two hippocampal-dependent tasks. A
      corresponding microarray analysis reveals that about 0.14% of hippocampal genes
      have an altered expression in the CPEB knockout mouse. These data suggest that
      CPEB-dependent local protein synthesis may be an important cellular mechanism
      underlying extinction of hippocampal-dependent memories.

PMID- 16452650
TI  - Beta1-adrenoceptor or alpha1-adrenoceptor activation initiates early odor
      preference learning in rat pups: support for the mitral cell/cAMP model of odor
      preference learning.
AB  - We proposed that mitral cell beta1-adrenoceptor activation mediates rat pup odor
      preference learning. Here we evaluate beta1-, beta2-, alpha1-, and alpha2
      adrenoceptor agonists in such learning. The beta1-adrenoceptor agonist,
      dobutamine, and the alpha1-adrenoceptor agonist, phenylephrine, induced learning,
      and both exhibited an inverted U-curve dose-response relationship to odor
      preference learning. Phenylephrine-induced learning occurred in the presence of
      propranolol to prevent indirect activation of beta-adrenoceptors. Alpha1
      adrenoceptor mediation may represent a novel mechanism inducing learning or may
      increase cAMP in mitral cells via indirect activation of GABA(B) receptors.
      Neither the beta2-adrenoceptor agonist, salbutamol, nor the alpha2-adrenoceptor
      agonist, clonidine, induced learning.

PMID- 16452651
TI  - Anisomycin infused into the hippocampus fails to block "reconsolidation" but
      impairs extinction: the role of re-exposure duration.
AB  - Recent studies have reported new evidence consistent with the hypothesis that
      reactivating a memory by re-exposure to a training context destabilizes the
      memory and induces "reconsolidation." In the present experiments, rats' memory
      for inhibitory avoidance (IA) training was tested 6 h (Test 1), 2 d (Test 2), and
      6 d (Test 3) after training. On Test 1 the rats were either removed from the
      shock compartment immediately after entry or retained in the shock context for
      200 sec, and intrahippocampal infusions of the protein synthesis inhibitor
      anisomycin (75 microg/side) were administered immediately after the test.
      Anisomycin infusions administered after Test 1 impaired IA performance on Test 2
      in animals given the brief re-exposure, but impaired extinction in animals
      exposed to the context for 200 sec. Rats with anisomycin-induced retention
      impairment on Test 2 demonstrated spontaneous recovery of retention performance
      on Test 3, whereas rats showing extinction on Test 2 showed further extinction on
      Test 3. The findings indicate that post-retrieval administration of anisomycin
      impairs subsequent retention performance only in the absence of extinction and
      that this impairment is temporary.

PMID- 16452652
TI  - Critical role of nitric oxide-cGMP cascade in the formation of cAMP-dependent
      long-term memory.
AB  - Cyclic AMP pathway plays an essential role in formation of long-term memory
      (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found
      to act in parallel and complementary to the cAMP pathway for LTM formation. Here
      we describe a new role of the NO-cGMP pathway, namely, stimulation of the cAMP
      pathway to induce LTM. We have studied the signaling cascade underlying LTM
      formation by systematically coinjecting various "LTM-inducing" and "LTM-blocking"
      drugs in crickets. Multiple-trial olfactory conditioning led to LTM that lasted
      for several days, while memory induced by single-trial conditioning decayed away
      within several hours. Injection of inhibitors of the enzyme forming NO, cGMP, or
      cAMP into the hemolymph prior to multiple-trial conditioning blocked LTM, whereas
      injection of an NO donor, cGMP analog, or cAMP analog prior to single-trial
      conditioning induced LTM. Induction of LTM by injection of an NO donor or cGMP
      analog paired with single-trial conditioning was blocked by inhibitors of the
      cAMP pathway, but induction of LTM by a cAMP analog was unaffected by inhibitors
      of the NO-cGMP pathway. Inhibitors of cyclic nucleotide-gated channel (CNG
      channel) or calmodulin-blocked induction of LTM by cGMP analog paired with single
      trial conditioning, but they did not affect induction of LTM by cAMP analog. Our
      findings suggest that the cAMP pathway is a downstream target of the NO-cGMP
      pathway for the formation of LTM, and that the CNG channel and calcium-calmodulin
      intervene between the NO-cGMP pathway and the cAMP pathway.

PMID- 16452655
TI  - Appetite for destruction: neuron ablations, prey capture, and sensorimotor
      integration in larval zebrafish.

PMID- 16452653
TI  - NMDA and muscarinic receptors of the nucleus accumbens have differential effects
      on taste memory formation.
AB  - Animals recognize a taste cue as aversive when it has been associated with post
      ingestive malaise; this associative learning is known as conditioned taste
      aversion (CTA). When an animal consumes a new taste and no negative consequences
      follow, it becomes recognized as a safe signal, leading to an increase in its
      consumption in subsequent presentations (attenuation of neophobia, AN). It has
      been shown that the nucleus accumbens (NAcc) has an important role in taste
      learning. To elucidate the involvement of N-methyl-D-aspartate (NMDA) and
      muscarinic receptors in the NAcc during safe and aversive taste memory formation,
      we administrated bilateral infusions of DL-2-amino-5-phosphonopentanoic acid
      (APV) or scopolamine in the NAcc shell or core respectively. Our results showed
      that pre-training injections of APV in the NAcc core and shell disrupted aversive
      but not safe taste memory formation, whereas pre-training injections of
      scopolamine in the NAcc shell, but not core, disrupted both CTA and AN. These
      results suggest that muscarinic receptors seem to be necessary for processing
      taste stimuli for either safe or aversive taste memory, whereas NMDA receptors
      are only involved in the aversive taste memory trace formation.

PMID- 16452656
TI  - Relating NMDA receptor function to receptor subunit composition: limitations of
      the pharmacological approach.

PMID- 16452654
TI  - 5-HT1a receptor antagonists block perforant path-dentate LTP induced in novel,
      but not familiar, environments.
AB  - Numerous studies suggest roles for monoamines in modulating long-term
      potentiation (LTP). Previously, we reported that both induction and maintenance
      of perforant path-dentate gyrus LTP is enhanced when induced while animals
      explore novel environments. Here we investigate the contribution of serotonin and
      5-HT1a receptors to the novelty-mediated enhancement of LTP. In freely moving
      animals, systemic administration of the selective 5-HT1a antagonist WAY-100635
      (WAY) attenuated LTP in a dose-dependent manner when LTP was induced while
      animals explored novel cages. In contrast, LTP was completely unaffected by WAY
      when induced in familiar environments. LTP was also blocked in anesthetized
      animals by direct application of WAY to the dentate gyrus, but not to the median
      raphe nucleus (MRN), suggesting the effect of systemic WAY is mediated by a block
      of dentate 5-HT1a receptors. Paradoxically, systemic administration of the 5-HT1a
      agonist 8-OH-DPAT also attenuated LTP. This attenuation was mimicked in
      anesthetized animals following application of 8-OH-DPAT to the MRN, but not the
      dentate gyrus. In addition, application of a 5-HT1a agonist to the dentate gyrus
      reduced somatic GABAergic inhibition. Because serotonergic projections from the
      MRN terminate on dentate inhibitory interneurons, these data suggest 5-HT1a
      receptors contribute to LTP induction via inhibition of GABAergic interneurons.
      Moreover, activation of raphe 5-HT1a autoreceptors, which inhibits serotonin
      release, attenuated LTP induction even in familiar environments. This suggests
      that serotonin normally contributes to dentate LTP induction in a variety of
      behavioral states. Together, these data suggest that serotonin and dentate 5-HT1a
      receptors play a permissive role in dentate LTP induction, particularly in novel
      conditions, and presumably, during the encoding of novel, hippocampus-relevant
      information.

PMID- 16452657
TI  - Intracranial delivery of CLN2 reduces brain pathology in a mouse model of
      classical late infantile neuronal ceroid lipofuscinosis.
AB  - Classical late infantile neuronal ceroid lipofuscinosis (cLINCL) is a lysosomal
      storage disorder caused by mutations in CLN2, which encodes lysosomal tripeptidyl
      peptidase I (TPP1). Lack of TPP1 results in accumulation of autofluorescent
      storage material and curvilinear bodies in cells throughout the CNS, leading to
      progressive neurodegeneration and death typically in childhood. In this study, we
      injected adeno-associated virus (AAV) vectors containing the human CLN2 cDNA into
      the brains of CLN2(-/-) mice to determine therapeutic efficacy. AAV2CUhCLN2 or
      AAV5CUhCLN2 were stereotaxically injected into the motor cortex, thalamus, and
      cerebellum of both hemispheres at 6 weeks of age, and mice were then killed at 13
      weeks after injection. Mice treated with AAV2CUhCLN2 and AAV5CUhCLN2 contained
      TPP1 activity at each injection tract that was equivalent to 0.5- and 2-fold that
      of CLN2(+/+) control mice, respectively. Lysosome-associated membrane protein 1
      immunostaining and confocal microscopy showed intracellular targeting of TPP1 to
      the lysosomal compartment. Compared with control animals, there was a marked
      reduction of autofluorescent storage in the AAV2CUhCLN2 and AAV5CUhCLN2 injected
      brain regions, as well as adjacent regions, including the striatum and
      hippocampus. Analysis by electron microscopy confirmed a significant decrease in
      pathological curvilinear bodies in cells. This study demonstrates that AAV
      mediated TPP1 enzyme replacement corrects the hallmark cellular pathologies of
      cLINCL in the mouse model and raises the possibility of using AAV gene therapy to
      treat cLINCL patients.

PMID- 16452658
TI  - Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor
      protein 23 transgenic mice.
AB  - Locus ceruleus (LC) degeneration and loss of cortical noradrenergic innervation
      occur early in Alzheimer's disease (AD). Although this has been known for several
      decades, the contribution of LC degeneration to AD pathogenesis remains unclear.
      We induced LC degeneration with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine
      (dsp4) in amyloid precursor protein 23 (APP23) transgenic mice with a low amyloid
      load. Then 6 months later the LC projection areas showed a robust elevation of
      glial inflammation along with augmented amyloid plaque deposits. Moreover,
      neurodegeneration and neuronal loss significantly increased. Importantly, the
      paraventricular thalamus, a nonprojection area, remained unaffected. Radial arm
      maze and social partner recognition tests revealed increased memory deficits
      while high-resolution magnetic resonance imaging-guided micro-positron emission
      tomography demonstrated reduced cerebral glucose metabolism, disturbed neuronal
      integrity, and attenuated acetylcholinesterase activity. Nontransgenic mice with
      LC degeneration were devoid of these alterations. Our data demonstrate that the
      degeneration of LC affects morphology, metabolism, and function of amyloid plaque
      containing higher brain regions in APP23 mice. We postulate that LC degeneration
      substantially contributes to AD development.

PMID- 16452659
TI  - Synaptic Ras GTPase activating protein regulates pattern formation in the
      trigeminal system of mice.
AB  - The development of ordered connections or "maps" within the nervous system is a
      common feature of sensory systems and is crucial for their normal function. NMDA
      receptors are known to play a key role in the formation of these maps; however,
      the intracellular signaling pathways that mediate the effects of glutamate are
      poorly understood. Here, we demonstrate that SynGAP, a synaptic Ras GTPase
      activating protein, is essential for the anatomical development of whisker
      related patterns in the developing somatosensory pathways in rodent forebrain.
      Mice lacking SynGAP show only partial segregation of barreloids in the thalamus,
      and thalamocortical axons segregate into rows but do not form whisker-related
      patches. In cortex, layer 4 cells do not aggregate to form barrels. In Syngap(+/
      ) animals, barreloids develop normally, and thalamocortical afferents segregate
      in layer 4, but cell segregation is retarded. SynGAP is not necessary for the
      development of whisker-related patterns in the brainstem. Immunoelectron
      microscopy for SynGAP from layer 4 revealed a postsynaptic localization with
      labeling in developing postsynaptic densities (PSDs). Biochemically, SynGAP
      associates with the PSD in a PSD-95-independent manner, and Psd-95(-/-) animals
      develop normal barrels. These data demonstrate an essential role for SynGAP
      signaling in the activity-dependent development of whisker-related maps
      selectively in forebrain structures indicating that the intracellular pathways by
      which NMDA receptor activation mediates map formation differ between brain
      regions and developmental stage.

PMID- 16452660
TI  - Physiological temperatures reduce the rate of vesicle pool depletion and short
      term depression via an acceleration of vesicle recruitment.
AB  - The timing and strength of synaptic transmission is profoundly dependent on
      temperature. However, the temperature dependence of the multiple mechanisms that
      contribute to short-term synaptic plasticity is poorly understood. Here, we use
      voltage-clamp recordings to quantify the temperature dependence of exocytosis at
      the calyx of Held synapse. EPSC and miniature EPSC amplitudes were larger at
      physiological temperature, but quantal content during low-frequency (0.05 Hz)
      stimulation was constant after temperature jumps from 22-24 degrees C to 35-37
      degrees C. The initial degree of EPSC depression during 100 Hz stimuli trains was
      unchanged with temperature, as were estimates of release probability and vesicle
      pool size. In contrast, physiological temperatures dramatically relieved
      depression measured after 40 stimuli at 100 Hz by increasing twofold the rate of
      recovery from depression. Presynaptic calyx recordings revealed that
      physiological temperature increased capacitance jumps resulting from 0.5 and 1 ms
      depolarizations by increasing Ca2+ influx. When Ca2+ entry was equalized at the
      two temperatures, exocytosis exhibited little temperature dependence for brief
      depolarizations. However, in response to longer depolarizations, raising
      temperature increased a slow phase of exocytosis, without affecting overall Ca2+
      entry or the size of the readily releasable pool of vesicles. Higher temperatures
      also increased the rate of presynaptic Ca2+ current inactivation; nevertheless,
      the degree of steady-state EPSC depression was greatly reduced. Our results thus
      suggest that changes in steady-state EPSCs during stimulus trains at
      physiological temperature reflect larger quantal amplitudes and faster refilling
      of synaptic vesicle pools, leading to reduced short-term depression during
      prolonged high-frequency firing.

PMID- 16452661
TI  - P2X7 receptors mediate ATP release and amplification of astrocytic intercellular
      Ca2+ signaling.
AB  - Modulation of synaptic transmission and brain microcirculation are new roles
      ascribed to astrocytes in CNS function. A mechanism by which astrocytes modify
      neuronal activity in the healthy brain depends on fluctuations of cytosolic Ca2+
      levels, which regulate the release of "gliotransmitters" via an exocytic pathway.
      Under pathological conditions, however, the participation of other pathways,
      including connexin hemichannels and the pore-forming P2X7R, have been proposed
      but remain controversial. Through the use of genetically modified 1321N1 human
      astrocytoma cells and of spinal cord astrocytes derived from neonatal Cx43- and
      P2X7R-null mice, we provide strong evidence that P2X7Rs, but not Cx43
      hemichannels, are sites of ATP release that promote the amplification of Ca2+
      signal transmission within the astrocytic network after exposure to low divalent
      cation solution. Moreover, our results showing that gap junction channel blockers
      (heptanol, octanol, carbenoxolone, flufenamic acid, and mefloquine) are
      antagonists of the P2X7R indicate the inadequacy of using these compounds as
      evidence for the participation of connexin hemichannels as sites of
      gliotransmitter release.

PMID- 16452662
TI  - Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid
      beta plaque deposition.
AB  - Pathophysiologic hypotheses for Alzheimer's disease (AD) are centered on the role
      of the amyloid plaque Abeta peptide and the mechanism of its derivation from the
      amyloid precursor protein (APP). As part of the disease process, an aberrant
      axonal sprouting response is known to occur near Abeta deposits. A Nogo to Nogo
      66 receptor (NgR) pathway contributes to determining the ability of adult CNS
      axons to extend after traumatic injuries. Here, we consider the potential role of
      NgR mechanisms in AD. Both Nogo and NgR are mislocalized in AD brain samples. APP
      physically associates with the NgR. Overexpression of NgR decreases Abeta
      production in neuroblastoma culture, and targeted disruption of NgR expression
      increases transgenic mouse brain Abeta levels, Abeta plaque deposition, and
      dystrophic neurites. Infusion of a soluble NgR fragment reduces Abeta levels,
      amyloid plaque deposits, and dystrophic neurites in a mouse transgenic AD model.
      Changes in NgR level produce parallel changes in secreted APPalpha and Abeta,
      implicating NgR as a blocker of secretase processing of APP. The NgR provides a
      novel site for modifying the course of AD and highlights the role of axonal
      dysfunction in the disease.

PMID- 16452664
TI  - The dopaminergic midbrain participates in human episodic memory formation:
      evidence from genetic imaging.
AB  - Recent data from animal studies raise the possibility that dopaminergic
      neuromodulation promotes the encoding of novel stimuli. We investigated a
      possible role for the dopaminergic midbrain in human episodic memory by measuring
      how polymorphisms in dopamine clearance pathways affect encoding-related brain
      activity (functional magnetic resonance imaging) in an episodic memory task. In
      51 young, healthy adults, successful episodic encoding was associated with
      activation of the substantia nigra. This midbrain activation was modulated by a
      functional variable number of tandem repeat (VNTR) polymorphism in the dopamine
      transporter (DAT1) gene. Despite no differences in memory performance between
      genotype groups, carriers of the (low expressing) 9-repeat allele of the DAT1
      VNTR showed relatively higher midbrain activation when compared with subjects
      homozygous for the 10-repeat allele, who express DAT1 at higher levels. The
      catechol-O-methyl transferase (COMT) Val108/158Met polymorphism, which is known
      to modulate enzyme activity, affected encoding-related activity in the right
      prefrontal cortex (PFC) and in occipital brain regions but not in the midbrain.
      Moreover, subjects homozygous for the (low activity) Met allele showed stronger
      functional coupling between the PFC and the hippocampus during encoding. Our
      finding that genetic variations in the dopamine clearance pathways affect
      encoding-related activation patterns in midbrain and PFC provides strong support
      for a role of dopaminergic neuromodulation in human episodic memory formation. It
      also supports the hypothesis of anatomically and functionally distinct roles for
      DAT1 and COMT in dopamine metabolism, with DAT1 modulating rapid, phasic midbrain
      activity and COMT being particularly involved in prefrontal dopamine clearance.

PMID- 16452663
TI  - The chloride transporter Na(+)-K(+)-Cl- cotransporter isoform-1 contributes to
      intracellular chloride increases after in vitro ischemia.
AB  - Ischemic episodes in the CNS cause significant disturbances in neuronal ionic
      homeostasis. To directly measure changes in intracellular Cl- concentration ([Cl
      ]i) during and after ischemia, we used Clomeleon, a novel ratiometric optical
      indicator for Cl-. Hippocampal slices from adult transgenic mice expressing
      Clomeleon in hippocampal neurons were subjected to 8 min of oxygen-glucose
      deprivation (OGD) (an in vitro model for ischemia) and reoxygenated in the
      presence of glucose. This produced mild neuronal damage 3 h later that was
      prevented when the extracellular [Cl-] was maintained at 10 mm during
      reoxygenation. OGD induced a transient decrease in fluorescence resonance energy
      transfer within Clomeleon, indicating an increase in [Cl-]i. During
      reoxygenation, there was a partial recovery in [Cl-]i, but [Cl-]i rose again 45
      min later. To investigate sources of Cl- accumulation, we examined the effects of
      Cl- transport inhibitors on the rises in [Cl-]i during and after OGD. Bumetanide
      and furosemide, which inhibit Cl- influx through the Na(+)-K(+)-Cl- cotransporter
      isoform-1 (NKCC-1) and efflux through the K(+)-Cl- cotransporter isoform-2, were
      unable to inhibit the first rise in [Cl-]i, yet entirely prevented the secondary
      rise in [Cl-]i during reoxygenation. In contrast, picrotoxin, which blocks the
      GABA-gated Cl- channel, did not inhibit the secondary rise in [Cl-]i after OGD.
      [Cl-]i increases during reoxygenation were accompanied by an increase in
      phosphorylation of NKCC-1, an indication of increased NKCC-1 activity after OGD.
      We conclude that NKCC-1 plays an important role in OGD-induced Cl- accumulation
      and subsequent neuronal damage.

PMID- 16452665
TI  - Rac1 and RhoA promote neurite outgrowth through formation and stabilization of
      growth cone point contacts.
AB  - Growth cone advance depends on coordinated membrane protrusion and adhesion to
      the extracellular matrix. Although many studies have addressed the mechanisms
      responsible for membrane protrusion, the assembly of integrin-dependent adhesion
      sites known as point contacts remains poorly understood in growth cones. We show
      balanced Rac1 activity controls both leading edge protrusion and point contact
      dynamics during neurite outgrowth. Immunocytochemistry and live imaging of
      paxillin-green fluorescent protein (GFP) showed that inhibiting Rac1 blocked
      point contact formation, whereas Rac1 overactivation produced small, unstable
      point contacts. Both inhibition and overactivation of Rac1 reduced the
      persistence of lamellar protrusions and neurite outgrowth. Inhibition of ROCK
      (Rho kinase), a RhoA effector, perturbed protrusion and point contact dynamics
      similar to Rac1 overactivation. Moreover, the repulsive guidance cue Semaphorin
      3A, which signals through Rac1, destabilizes point contacts. Together, our data
      suggest that coordinated Rho GTPase activities regulate neurite outgrowth through
      point contact formation and stabilization of membrane protrusion.

PMID- 16452666
TI  - Between-task competition and cognitive control in task switching.
AB  - Cognitive control is required to regulate interactions between brain regions to
      produce effective, purposeful behavior. We used functional magnetic resonance
      imaging to investigate the nature of these interactions and the role of
      prefrontal cortex (PFC) in cognitive control as subjects switched between simple
      face and word categorization tasks. Face and word stimuli were used because
      previous research has shown them to activate distinguishable cortical regions,
      allowing us to measure levels of activity in task-selective brain regions during
      task switching. We found that activity in brain regions selective for the
      currently irrelevant task predicted the behavioral cost associated with switching
      tasks. This finding supports the theory that between-task competition is a
      critical determinant of behavior. Task switching was also associated with
      increased activity in a network of regions implicated in cognitive control,
      including lateral PFC and parietal cortex. Within this network of regions, we
      observed dissociations between task-selective and general purpose mechanisms.
      These findings provide support for theories that propose a control hierarchy
      comprising regions responsible for maintaining task-specific information about
      rules or goals, and regions involved in the coordination of these goals.

PMID- 16452667
TI  - Proliferation and death of oligodendrocytes and myelin proteins are
      differentially regulated in male and female rodents.
AB  - Sexual dimorphism of neurons and astrocytes has been demonstrated in different
      centers of the brain, but sexual dimorphism of oligodendrocytes and myelin has
      not been examined. We show, using immunocytochemistry and in situ hybridization,
      that the density of oligodendrocytes in corpus callosum, fornix, and spinal cord
      is 20-40% greater in males compared with females. These differences are present
      in young and aged rodents and are independent of strain and species. Proteolipid
      protein and carbonic anhydrase-II transcripts, measured by real-time PCR, are
      approximately two to three times greater in males. Myelin basic protein and 2',
      3'-cyclic nucleotide 3'-phosphodiesterase, measured by Western blots, are 20-160%
      greater in males compared with females. Surprisingly, both generation of new glia
      and apoptosis of glia, including oligodendrocytes, are approximately two times
      greater in female corpus callosum. These results indicate that the lifespan of
      oligodendrocytes is shorter in females than in males. Castration of males
      produces a female phenotype characterized by fewer oligodendrocytes and increased
      generation of new glia. These findings indicate that exogenous androgens
      differentially affect the lifespan of male and female oligodendrocytes, and they
      can override the endogenous production of neurosteroids. The data imply that
      turnover of myelin is greater in females than in males. Mu-calpain, a protease
      upregulated in degeneration of myelin, is dramatically increased at both
      transcriptional and translational levels in females compared with males. These
      morphological, molecular, and biochemical data show surprisingly large
      differences in turnover of oligodendrocytes and myelin between sexes. We discuss
      the potential significance of these differences to multiple sclerosis, a sexually
      dimorphic disease, whose progression is altered by exogenous hormones.

PMID- 16452669
TI  - The dopamine D3 receptor is part of a homeostatic pathway regulating ethanol
      consumption.
AB  - We recently identified a homeostatic pathway that inhibits ethanol intake. This
      protective pathway consists of the scaffolding protein RACK1 and brain-derived
      neurotrophic factor (BDNF). RACK1 translocates to the nucleus after exposure of
      neurons to ethanol and increases expression of BDNF (McGough et al., 2004). We
      also found that increasing the levels of BDNF via systemic administration of
      RACK1 expressed as a Tat-fusion protein (Tat-RACK1) reduces ethanol consumption,
      whereas reduction of BDNF levels augments this behavior (McGough et al., 2004).
      Based on these results, we hypothesized that activation of the BDNF receptor TrkB
      is necessary for the effects of BDNF on ethanol intake and that gene products
      downstream of BDNF negatively regulate ethanol consumption. Here, we show that
      inhibition of the BDNF receptor TrkB increases voluntary ethanol consumption in
      wild-type mice but not in mice lacking one copy of the BDNF gene (BDNF(+/-)). We
      also find that increases in the levels of BDNF, mediated by ethanol or RACK1,
      lead to increased dorsal striatal levels of the dopamine D3 receptor (D3R), a
      gene downstream of BDNF, via activation of the TrkB receptor. Finally, we show
      that the Tat-RACK1-mediated reduction of ethanol consumption is attenuated by
      coinjection with either the Trk inhibitor K252a or the dopamine D3R-prefering
      antagonist U-99194A [5, 6-dimethoxy-2-(di-n-propylamino)indan], suggesting that
      activation of the BDNF pathway via RACK1 leads to increased expression of the
      dopamine D3R, which in turn mediates the attenuation of ethanol consumption.

PMID- 16452668
TI  - The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan
      3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress
      by acting through estrogen receptor beta-expressing neurons in the hypothalamus.
AB  - Estrogen receptor beta (ERbeta) and androgen receptor (AR) are found in high
      levels within populations of neurons in the hypothalamus. To determine whether AR
      or ERbeta plays a role in regulating hypothalamo-pituitary-adrenal (HPA) axis
      function by direct action on these neurons, we examined the effects of central
      implants of 17beta-estradiol (E2), 5alpha-dihydrotestosterone (DHT), the DHT
      metabolite 5alpha-androstan-3beta, 17beta-diol (3beta-diol), and several ER
      subtype-selective agonists on the corticosterone and adrenocorticotropin (ACTH)
      response to immobilization stress. In addition, activation of neurons in the
      paraventricular nucleus (PVN) was monitored by examining c-fos mRNA expression.
      Pellets containing these compounds were stereotaxically implanted near the PVN of
      gonadectomized male rats. Seven days later, animals were killed directly from
      their home cage (nonstressed) or were restrained for 30 min (stressed) before
      they were killed. Compared with controls, E2 and the ERalpha-selective agonists
      moxestrol and propyl-pyrazole-triol significantly increased the stress induced
      release of corticosterone and ACTH. In contrast, central administration of DHT,
      3beta-diol, and the ERbeta-selective compound diarylpropionitrile significantly
      decreased the corticosterone and ACTH response to immobilization. Cotreatment
      with the ER antagonist tamoxifen completely blocked the effects of 3beta-diol and
      partially blocked the effect of DHT, whereas the AR antagonist flutamide had no
      effect. Moreover, DHT, 3beta-diol, and diarylpropionitrile treatment
      significantly decreased restraint-induced c-fos mRNA expression in the PVN.
      Together, these studies indicate that the inhibitory effects of DHT on HPA axis
      activity may be in part mediated via its conversion to 3beta-diol and subsequent
      binding to ERbeta.

PMID- 16452670
TI  - Presynaptic, activity-dependent modulation of cannabinoid type 1 receptor
      mediated inhibition of GABA release.
AB  - Endocannabinoid signaling couples activity-dependent rises in postsynaptic Ca2+
      levels to decreased presynaptic GABA release. Here, we present evidence from
      paired recording experiments that cannabinoid-mediated inhibition of GABA release
      depends on the firing rates of the presynaptic interneurons. Low-frequency action
      potentials in post hoc identified cholecystokinin-positive CA1 basket cells
      elicited IPSCs in the postsynaptic pyramidal cells that, as expected, were fully
      abolished by the exogenous application of the cannabinoid receptor agonist
      WIN55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]
      1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate] at 5 microM.
      However, the presynaptic basket cells recovered from the cannabinoid agonist
      induced inhibition of GABA release when the presynaptic firing rate was increased
      to > or =20 Hz. Pharmacological experiments showed that the recovered
      transmission was exclusively dependent on presynaptic N-type Ca2+ channels.
      Furthermore, the increased presynaptic firing could also overcome even complete
      depolarization-induced suppression of inhibition, indicating that the magnitude
      of DSI markedly depends on the activity levels of basket cells. These results
      reveal a new locus of activity-dependent modulation for endocannabinoid signaling
      and suggest that endocannabinoid-mediated inhibition of GABA release may differ
      in distinct behavioral states.

PMID- 16452671
TI  - Neuromechanics of coordination during swallowing in Aplysia californica.
AB  - Bernstein (1967) hypothesized that preparation of the periphery was crucial for
      correct responses to motor output. To test this hypothesis in a behaving animal,
      we examined the roles of two identified motor neurons, B7 and B8, which
      contribute to feeding behavior in the marine mollusk Aplysia californica. Neuron
      B7 innervates a hinge muscle and has no overt behavioral effect during smaller
      amplitude (type A) swallows, because the hinge muscle is too short to exert
      force. Neuron B8 activates a muscle (I4) that acts solely to grasp material
      during type A swallows. During larger-amplitude (type B) swallows, the behavioral
      actions of both motor neurons change, because the larger-amplitude anterior
      movement of the grasper sets up the periphery to respond differently to motor
      outputs. The larger anterior movement stretches the hinge muscle, so that
      activating neuron B7 mediates the initial retraction phase of swallowing. The
      changed position of the I4 muscle allows neuron B8 not only to induce grasping
      but also to pull material into the buccal cavity, contributing to retraction.
      Thus, larger-amplitude swallows are associated with the expression of two new
      degrees of freedom (use of the hinge to retract and use of the grasper to
      retract) that are essential for mediating type B swallows. These results provide
      a direct demonstration of Bernstein's hypothesis that properly positioning the
      periphery can be crucial for its ability to correctly respond to motor output and
      also demonstrate that biomechanical context can alter the functions of identified
      motor neurons.

PMID- 16452673
TI  - Delta subunit susceptibility variants E177A and R220H associated with complex
      epilepsy alter channel gating and surface expression of alpha4beta2delta GABAA
      receptors.
AB  - Most human idiopathic generalized epilepsies (IGEs) are polygenic, but virtually
      nothing is known of the molecular basis for any of the complex epilepsies.
      Recently, two GABAA receptor delta subunit variants (E177A, R220H) were proposed
      as susceptibility alleles for generalized epilepsy with febrile seizures plus and
      juvenile myoclonic epilepsy. In human embryonic kidney 293T cells, recombinant
      halpha1beta2delta(E177A) and halpha1beta2delta(R220H) receptor currents were
      reduced, but the basis for the current reduction was not determined. We examined
      the mechanistic basis for the current reduction produced by these variants using
      the halpha4beta2delta receptor, an isoform more physiologically relevant and
      linked to epileptogenesis, by characterizing the effects of these variants on
      receptor cell surface expression and single-channel gating properties. Expression
      of variant alpha4beta2delta(R220H) receptors resulted in a decrease in surface
      receptor proteins, and a smaller, but significant, reduction was observed for
      variant alpha4beta2delta(E177A) receptors. For both variants, no significant
      alterations of surface expression were observed for mixed population of wild-type
      and variant receptors. The mean open durations of alpha4beta2delta(E177A) and
      alpha4beta2delta(R220H) receptor single-channel currents were both significantly
      decreased compared to wild-type receptors. These data suggest that both
      delta(E177A) and delta(R220H) variants may result in disinhibition in IGEs by
      similar cellular and molecular mechanisms, and in heterozygously affected
      individuals, a reduction in channel open duration of delta subunit-containing
      GABAA receptors may be the major contributor to the epilepsy phenotypes.

PMID- 16452672
TI  - Coordination and modulation of locomotion pattern generators in Drosophila
      larvae: effects of altered biogenic amine levels by the tyramine beta hydroxlyase
      mutation.
AB  - Forward locomotion of Drosophila melanogaster larvae is composed of rhythmic
      waves of contractions that are thought to be produced by segmentally organized
      central pattern generators. We present a systematic description of spike activity
      patterns during locomotive contraction waves in semi-intact wild-type and mutant
      larval preparations. We have shown previously that Tbetah(nM18) mutants, with
      altered levels of octopamine and tyramine, have a locomotion deficit. By
      recording en passant from the segmental nerves, we investigated the coordination
      of the neuronal activity driving contraction waves of the abdominal body-wall
      muscles. Rhythmic bursts of activity that occurred concurrently with locomotive
      waves were frequently observed in wild-type larvae but were rarely seen in
      Tbetah(nM18) mutants. These centrally generated patterned activities were
      eliminated in the distal stumps of both wild-type and Tbetah(nM18) larvae after
      severing the segmental nerve from the CNS. Patterned activities persisted in the
      proximal stumps deprived of sensory feedback from the periphery. Simultaneous
      recordings demonstrated a delay in the bursting activity between different
      segments, with greater delay for segments that were farther apart. In contrast,
      bilateral recordings within a single segment revealed a well synchronized
      activity pattern in nerves innervating each hemisegment in both wild-type and
      Tbetah(nM18) larvae. Significantly, rhythmic patterns of bursts and waves could
      be evoked in Tbetah(nM18) mutants by head or tail stimulation despite their
      highly irregular spontaneous activities. These observations suggest a role of the
      biogenic amines in the initiation and modulation of motor pattern generation. The
      technique presented here can be readily extended to examine the locomotion motor
      program of other mutants.

PMID- 16452675
TI  - Long-term adeno-associated viral vector-mediated expression of truncated TrkB in
      the adult rat facial nucleus results in motor neuron degeneration.
AB  - Adult facial motor neurons continue to express full-length TrkB tyrosine kinase
      receptor (TrkB.FL), the high-affinity receptor for the neurotrophins BDNF and
      neurotrophic factor-4/5 (NT-4/5), suggesting that they remain dependent on target
      derived and locally produced neurotrophins in adulthood. Studies on the role of
      TrkB signaling in the adult CNS have been hampered by the early lethality of
      bdnf, nt-4/5, and trkB knock-out mice. We disrupted TrkB.FL signaling in adult
      facial motor neurons using adeno-associated viral vector-mediated overexpression
      of a naturally occurring dominant-negative TrkB receptor, TrkB.T1. Expression of
      TrkB.T1 resulted in neuronal atrophy and downregulation of NeuN (neuronal
      specific nuclear protein) and ChAT expression in facial motor neurons. A subset
      of transduced neurons displayed signs of motor neuron degeneration that included
      dendritic beading and rounding of the soma at 2 months of TrkB.T1 expression.
      Cell counts revealed a significant reduction in motor neuron number in the facial
      nucleus at 4 months after onset of expression of TrkB.T1, suggesting that a
      proportion of TrkB.T1-expressing motor neurons became undetectable as a result of
      severe atrophy or was lost because of cell death. In contrast, overexpression of
      TrkB.FL did not result in a decrease in facial motor neuron number. Our results
      indicate that a subset of facial motor neurons remains dependent on TrkB ligands
      for the maintenance of structural and molecular characteristics in adulthood.

PMID- 16452674
TI  - Fornix lesions decouple the induction of hippocampal arc transcription from
      behavior but not plasticity.
AB  - The immediate-early gene (IEG) Arc is transcribed after behavioral and
      physiological treatments that induce synaptic plasticity and is implicated in
      memory consolidation. The relative contributions of neuronal activity and
      learning-related plasticity to the behavioral induction of Arc remain to be
      defined. To differentiate the contributions of each, we assessed the induction of
      Arc transcription in rats with fornix lesions that impair hippocampal learning
      yet leave cortical connectivity and neuronal firing essentially intact. Arc
      expression was assessed after exploration of novel environments and performance
      of a novel water maze task during which normal rats learned the spatial location
      of an escape platform. During the same task, rats with fornix lesions learned to
      approach a visible platform but did not learn its spatial location. Rats with
      fornix lesions had normal baseline levels of hippocampal Arc mRNA, but unlike
      normal rats, expression was not increased in response to water maze training. The
      integrity of signaling pathways controlling Arc expression was demonstrated by
      stimulation of the medial perforant path, which induced normal synaptic
      potentiation and Arc in rats with fornix lesions. Together, the results
      demonstrate that Arc induction can be decoupled from behavior and is more likely
      to indicate the engagement of synaptic plasticity mechanisms than synaptic or
      neuronal activity per se. The results further imply that fornix lesions may
      impair memory in part by decoupling neuronal activity from signaling pathways
      required for long-lasting hippocampal synaptic plasticity.

PMID- 16452676
TI  - Retinoid-related orphan receptor alpha controls the early steps of Purkinje cell
      dendritic differentiation.
AB  - Dendritic differentiation involves both regressive and growth events. The
      mechanisms controlling the regressive events are poorly understood. This study is
      aimed at determining the role of the nuclear receptor retinoid-related orphan
      receptor alpha (RORalpha) in Purkinje cell (PC) dendritic differentiation in
      organotypic cultures. As observed in vivo, in these cultures, fusiform PCs with
      embryonic bipolar shape undergo regression before the outgrowth of the ultimate
      dendritic tree. We show that lentiviral-mediated hRORalpha1 overexpression in
      fusiform PCs leads to a cell-autonomous accelerated progression of dendritic
      differentiation. In addition, RORalpha is necessary for the PC regressive events:
      whereas staggerer RORalpha-deficient PCs remain in the embryonic fusiform stage,
      replacement of hRORalpha1 restores normal dendritogenesis. These results
      demonstrate that RORalpha expression in fusiform PCs is crucial for the dendritic
      regression and progression of the following step of extension of dendritic
      processes. However, it does not seem to participate to the last stage of
      dendritic growth. This study identifies RORalpha as a nuclear receptor crucial
      for the control of dendritic remodeling during development.

PMID- 16452677
TI  - The level and integrity of synaptic input regulates dendrite structure.
AB  - How localized synaptic input regulates dendritic branch structure is not well
      understood. For these experiments, we used single-cell electroporation, live cell
      imaging, in vitro deafferentation, pharmacology, and electrophysiological
      stimulation to study how local alterations in synaptic input affect dendritic
      branch structure in nucleus laminaris (NL). We found that interrupting or
      modulating synaptic input to distinct sets of NL dendrites can regulate their
      structure on a very short timescale. Specifically, eliminating synaptic input by
      deafferenting only one set of the bitufted NL dendrites caused a selective
      reduction in the total dendritic branch length of the deafferented dendrites but
      relatively few changes in the normally innervated dendrites on the same cell. An
      analysis of individual dendritic branch changes demonstrated that both control
      and deafferented NL dendrites exhibit branch extension and retraction. However,
      the presence of intact synaptic inputs balanced these changes, maintaining the
      total dendritic branch length of control dendrites. When glutamate receptor
      signaling was blocked (DNQX and AP-5), NL neurons exhibited significant dendrite
      retraction, demonstrating that NL dendrite maintenance depends in part on
      presynaptic glutamatergic input. Electrophysiological experiments further
      confirmed that modulating the level of synaptic input regulates NL dendrite
      structure. Differential stimulation of the two sets of dendrites resulted in a
      selective reduction in the total dendritic branch length of the unstimulated
      dendrites and a selective increase in the total dendritic branch length of the
      stimulated dorsal dendrites. These results suggest that balanced activation of
      the two sets of NL dendrites is required to maintain the relative amount of
      dendritic surface area allotted to each input.

PMID- 16452678
TI  - The endocannabinoid system promotes astroglial differentiation by acting on
      neural progenitor cells.
AB  - Endocannabinoids exert an important neuromodulatory role via presynaptic
      cannabinoid CB1 receptors and may also participate in the control of neural cell
      death and survival. The function of the endocannabinoid system has been
      extensively studied in differentiated neurons, but its potential role in neural
      progenitor cells remains to be elucidated. Here we show that the CB1 receptor and
      the endocannabinoid-inactivating enzyme fatty acid amide hydrolase are expressed,
      both in vitro and in vivo, in postnatal radial glia (RC2+ cells) and in adult
      nestin type I (nestin(+)GFAP+) neural progenitor cells. Cell culture experiments
      show that CB1 receptor activation increases progenitor proliferation and
      differentiation into astroglial cells in vitro. In vivo analysis evidences that,
      in postnatal CB1(-/-) mouse brain, progenitor proliferation and astrogliogenesis
      are impaired. Likewise, in adult CB1-deficient mice, neural progenitor
      proliferation is decreased but is increased in fatty acid amide hydrolase
      deficient mice. In addition, endocannabinoid signaling controls neural progenitor
      differentiation in the adult brain by promoting astroglial differentiation of
      newly born cells. These results show a novel physiological role of
      endocannabinoids, which constitute a new family of signaling cues involved in the
      regulation of neural progenitor cell function.

PMID- 16452679
TI  - Hippocampal CA3 NMDA receptors are crucial for adaptive timing of trace eyeblink
      conditioned response.
AB  - Classical conditioning of the eyeblink reflex is a simple form of associative
      learning for motor responses. To examine the involvement of hippocampal CA3 NMDA
      receptors (NRs) in nonspatial associative memory, mice lacking an NR1 subunit
      selectively in adult CA3 pyramidal cells [CA3-NR1 knock-out (KO) mice] were
      subjected to eyeblink conditioning paradigms. Mice received paired presentations
      of an auditory conditioned stimulus (CS) and a periorbital shock unconditioned
      stimulus (US). With repeated presentation of the CS followed by the US, wild-type
      mice learned to blink in anticipation of the US before its onset. We first
      confirmed that wild-type mice require an intact hippocampus in the trace version
      of eyeblink conditioning in which the CS and US do not overlap, creating a
      stimulus-free time gap of 500 ms. Under the same condition, CA3-NR1 KO mice
      successfully acquired conditioned responses (CRs) during the 10 d acquisition
      sessions, whereas the extinction of CRs was impaired on the first day of
      extinction sessions. Importantly, CA3-NR1 KO mice were impaired in the formation
      of an adaptively timed CR during the first five trials in the daily acquisition
      sessions. The aberrantly timed CR was also observed in the extinction sessions in
      accordance with the impaired extinction of CRs. These results indicate that CA3
      NR1 KO mice are unable to rapidly retrieve adaptive CR timing, suggesting that
      CA3 NRs play a crucial role in the memory of adaptive CR timing in trace
      conditioning.

PMID- 16452680
TI  - Chronic stress increases the plasmalemmal distribution of the norepinephrine
      transporter and the coexpression of tyrosine hydroxylase in norepinephrine axons
      in the prefrontal cortex.
AB  - Norepinephrine (NE) potently modulates the cognitive and affective functions of
      the prefrontal cortex (PFC). Deficits in NE transmission are implicated in
      psychiatric disorders, and antidepressant drugs that block the NE transporter
      (NET) effectively treat these conditions. Our initial ultrastructural studies of
      the rat PFC revealed that most NE axons (85-90%) express NET primarily within the
      cytoplasm and lack detectable levels of the synthetic enzyme tyrosine hydroxylase
      (TH). In contrast, the remaining 10-15% of PFC NE axons exhibit predominantly
      plasmalemmal NET and evident TH immunoreactivity. These unusual characteristics
      suggest that most PFC NE axons have an unrecognized, latent capacity to enhance
      the synthesis and recovery of transmitter. In the present study, we used dual
      labeling immunocytochemistry and electron microscopy to examine whether chronic
      cold stress, a paradigm that persistently increases NE activity, would trigger
      cellular changes consistent with this hypothesis. After chronic stress, neither
      the number of profiles exhibiting NET labeling nor their size was changed.
      However, the proportion of plasmalemmal NET nearly doubled from 29% in control
      animals to 51% in stressed rats. Moreover, the expression of detectable TH in NET
      labeled axons increased from only 13% of profiles in control rats to 32% of
      profiles in stressed animals. Despite the consistency of these findings, the
      magnitude of the changes varied across individual rats. These data represent the
      first demonstration of activity-dependent trafficking of NET and expression of TH
      under physiological conditions and have important implications for understanding
      the pathophysiology and treatment of stress-related affective disorders.

PMID- 16452681
TI  - Cocaine increases actin cycling: effects in the reinstatement model of drug
      seeking.
AB  - Addiction to cocaine is associated with persistent changes in synaptic function.
      The cycling of actin between polymerized [F (for filamentous)] and depolymerized
      forms contributes to synaptic plasticity, and acute and withdrawal from repeated
      cocaine administration produced reversible and enduring elevations, respectively,
      in F-actin in the nucleus accumbens. Increased F-actin after 3 weeks withdrawal
      from repeated cocaine resulted from changes in the content or phosphorylation
      state of actin binding proteins (ABPs) that cosediment with F-actin. The profile
      of altered APBs was consistent with filopodia formation, including increased
      mammalian Enabled, phosphorylated (p)-cortactin, and p-vasodilator-stimulated
      phosphoprotein, and increased actin depolymerization [e.g., reduced LIM
      (Lin11/Isl-1/Mec3)-kinase and p-cofilin]. In contrast to repeated cocaine, the
      increase in F-actin after acute cocaine administration resulted from reduced
      depolymerization and actin cycling. The potential involvement of chronic cocaine
      induced increases in actin cycling in cocaine addiction was examined using the
      reinstatement of cocaine seeking in rats previously trained to self-administer
      cocaine by inhibiting actin polymerization with intra-accumbens latrunculin A or
      by accelerating actin depolymerization with a LIM-kinase inhibitor. Disrupting
      actin cycling via either mechanism augmented cocaine-induced reinstatement of
      drug seeking but did not affect the locomotor response to acute cocaine
      administration. Thus, withdrawal from repeated cocaine induces a restructuring of
      actin-ABP complexes, which increases actin cycling and may modulate cocaine
      induced reinstatement of drug seeking.

PMID- 16452682
TI  - Simultaneous release of glutamate and acetylcholine from single magnocellular
      "cholinergic" basal forebrain neurons.
AB  - Basal forebrain (BF) neurons provide the principal cholinergic drive to the
      hippocampus and cortex. Their degeneration is associated with the cognitive
      defects of Alzheimer's disease. Immunohistochemical studies suggest that some of
      these neurons contain glutamate, so might also release it. To test this, we made
      microisland cultures of single BF neurons from 12- to 14-d-old rats. Over 1-8
      weeks in culture, neuronal processes made autaptic connections onto the neuron.
      In 34 of 36 cells tested, a somatically generated action potential was followed
      by a short-latency EPSC that was blocked by 1 mM kynurenic acid, showing that
      they released glutamate. To test whether the same neuron also released
      acetylcholine, we placed a voltage-clamped rat myoball expressing nicotinic
      receptors in contact with a neurite. In six of six neurons tested, the
      glutamatergic EPSC was accompanied by a nicotinic (hexamethonium-sensitive)
      myoball current. Stimulation of the M2-muscarinic presynaptic receptors
      (characterized using tripitramine and pirenzepine) produced a parallel inhibition
      of autaptic glutamatergic and myoball nicotinic responses; metabotropic glutamate
      receptor stimulation produced similar but less consistent and weaker effects.
      Atropine enhanced the glutamatergic EPSCs during repetitive stimulation by 25 +/-
      6%; the anti-cholinesterase neostigmine reduced the train EPSCs by 37 +/- 6%.
      Hence, synaptically released acetylcholine exerted a negative-feedback inhibition
      of coreleased glutamate. We conclude that most cholinergic basal forebrain
      neurons are capable of releasing glutamate as a cotransmitter and that the
      release of both transmitters is subject to simultaneous feedback inhibition by
      synaptically released acetylcholine. This has implications for BF neuron function
      and for the use of cholinesterase inhibitors in Alzheimer's disease.

PMID- 16452683
TI  - The lipoprotein receptor LR11 regulates amyloid beta production and amyloid
      precursor protein traffic in endosomal compartments.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive cognitive decline and neuropathological changes, including the
      deposition of amyloid beta (Abeta) in senile plaques. The mechanisms causing the
      disease and Abeta accumulation are not well understood, but important genetic
      associations with apolipoprotein E genotype and involvement of lipoprotein
      receptors have become apparent. LR11 (also known as SorLA), a member of the low
      density lipoprotein receptor family, has been identified previously as an altered
      transcript in microarray analyses of samples from human AD cases. Here, we show
      neuronal expression of the lipoprotein receptor LR11 in control brain in regions
      vulnerable to AD neuropathology and marked reduction of LR11 expression in these
      regions in AD brains before cell death. Overexpression of LR11 drastically
      reduces levels of extracellular Abeta and also lowers levels of total cellular
      amyloid precursor protein (APP). LR11 colocalizes with APP and regulates its
      trafficking in endocytic compartments, which are important intracellular sites
      for APP processing and Abeta generation. Endogenous LR11 localizes to neuronal
      multivesicular bodies in both rat and human brain. The robust correlation between
      reduced LR11 expression and AD neuropathology and its potent effects on
      extracellular Abeta levels suggest that this neuronal lipoprotein receptor could
      play an important role in AD pathogenesis.

PMID- 16452684
TI  - A specific role for NR2A-containing NMDA receptors in the maintenance of
      parvalbumin and GAD67 immunoreactivity in cultured interneurons.
AB  - Several lines of evidence suggest that a hypoglutamatergic condition may induce a
      phenotypic loss of cortical parvalbumin (PV)-positive GABAergic interneurons,
      such as that observed in brain tissue of schizophrenic subjects. However, it is
      not known whether the loss of PV interneurons is a consequence of the
      hypoglutamatergic condition or a secondary aspect of the disease. We
      characterized the signaling and subunit expression of NMDA receptors in cultured
      cortical PV interneurons and determined whether a hypoglutamatergic condition,
      created by direct application of sublethal concentrations of ketamine or subunit
      selective NMDA receptor antagonists, can affect the expression of the GABAergic
      markers as observed in vivo. Real-time PCR performed on mRNA isolated from single
      neurons showed that PV interneurons present a fivefold higher NR2A/NR2B ratio
      than pyramidal neurons. Brief, nontoxic, exposure to NMDA led to an increase in
      ERK1/2 (extracellular signal-regulated kinase 1/2) and cAMP response element
      binding protein phosphorylation in PV interneurons, and this increase was blocked
      by the NR2A-selective antagonist NVP-AAM077. Application of the nonselective NMDA
      receptor antagonist ketamine, at sublethal concentrations, induced a time and
      dose-dependent decrease in parvalbumin and GAD67 immunoreactivity specifically in
      PV interneurons. These effects were reversible and were also observed with the
      NR2A-selective antagonist, whereas the NR2B-selective antagonist Ro-25-6981 only
      partially reduced GAD67 immunoreactivity. Coexposure to the calcium channel
      opener BayK, or the group I metabotropic glutamate receptor agonist DHPG [(RS)
      3,5-dihydroxyphenylglycine] attenuated the decrease in GAD67 and parvalbumin
      induced by the NMDA receptor antagonists. These results suggest that the activity
      of NR2A-containing NMDA receptors play a pivotal role in the maintenance of the
      GABAergic function of PV interneurons.

PMID- 16452685
TI  - Amygdala regulation of immediate-early gene expression in the hippocampus induced
      by contextual fear conditioning.
AB  - The basolateral nuclei of the amygdala (BLA) are thought to modulate memory
      storage in other brain regions (McGaugh, 2004). We reported that BLA modulates
      the memory for both an explored context and for contextual fear conditioning.
      Both of these memories depend on the hippocampus. Here, we examined the
      hypothesis that the BLA exerts its modulatory effect by regulating the expression
      of immediate-early genes (IEGs) in the hippocampus. The main findings of these
      experiments were: (1) Arc activity-regulated cytoskeletal protein (Arc), an
      immediate-early gene (also termed Arg 3.1) and c-fos mRNA are induced in the
      hippocampus after a context exposure, or context plus shock experience, but not
      after an immediate shock; and (2) BLA inactivation with muscimol attenuated the
      increase in Arc and c-fos mRNA in the hippocampus associated with contextual fear
      conditioning but did not influence Arc mRNA associated with context exploration.
      These results support the hypothesis that the amygdala modulates contextual fear
      memory by regulating expression of IEGs in the hippocampus.

PMID- 16452686
TI  - Regulation of the neuronal proteasome by Zif268 (Egr1).
AB  - Most forms of neuronal plasticity are associated with induction of the
      transcription factor Zif268 (Egr1/Krox24/NGF-IA). In a genome-wide scan, we
      obtained evidence for potential modulation of proteasome subunit and regulatory
      genes by Zif268 in neurons, a finding of significance considering emerging
      evidence that the proteasome modulates synaptic function. Bioinformatic analysis
      indicated that the candidate proteasome Zif268 target genes had a rich
      concentration of putative Zif268 binding sites immediately upstream of the
      transcriptional start sites. Regulation of the mRNAs encoding the psmb9 (Lmp2)
      and psme2 (PA28beta) proteasome subunits, along with the proteasome-regulatory
      kinase serum/glucocorticoid-regulated kinase (SGK) and the proteasome-associated
      antigen peptide transporter subunit 1 (Tap1), was confirmed after transfection of
      a neuronal cell line with Zif268. Conversely, these mRNAs were upregulated in
      cerebral cortex tissue from Zif268 knock-out mice relative to controls,
      confirming that Zif268 suppresses their expression in the CNS. Transfected Zif268
      reduced the activity of psmb9, SGK, and Tap1 promoter-reporter constructs.
      Altered psmb9, SGK, and Tap1 mRNA levels were also observed in an in vivo model
      of neuronal plasticity involving Zif268 induction: the effect of haloperidol
      administration on striatal gene expression. Consistent with these effects on
      proteasome gene expression, increased Zif268 expression suppressed proteasome
      activity, whereas Zif268 knock-out mice exhibited elevated cortical proteasome
      activity. Our findings reveal that Zif268 regulates the expression of proteasome
      and related genes in neuronal cells and provide new evidence that altered
      expression of proteasome activity after Zif268 induction may be a key component
      of long-lasting CNS plasticity.

PMID- 16452687
TI  - Inhibition of calcineurin by FK506 protects against polyglutamine-huntingtin
      toxicity through an increase of huntingtin phosphorylation at S421.
AB  - Huntington's disease (HD) is caused by an abnormal expanded polyglutamine (polyQ)
      repeat in the huntingtin protein. Insulin-like growth factor-1 acting through the
      prosurvival kinase Akt mediates the phosphorylation of huntingtin at S421 and
      inhibits the toxicity of polyQ-expanded huntingtin in cell culture, suggesting
      that compounds enhancing phosphorylation are of therapeutic interest. However, it
      is not clear whether phosphorylation of S421 is crucial in vivo. Using a rat
      model of HD based on lentiviral-mediated expression of a polyQ-huntingtin
      fragment in the striatum, we demonstrate here that phosphorylation of S421 is
      neuroprotective in vivo. We next demonstrate that calcineurin (CaN), a
      calcium/calmodulin-regulated Ser/Thr protein phosphatase, dephosphorylates S421
      in vitro and in cells. Inhibition of calcineurin activity, either by
      overexpression of the dominant-interfering form of CaN or by treatment with the
      specific inhibitor FK506, favors the phosphorylation of S421, restores the
      alteration in huntingtin S421 phosphorylation in HD neuronal cells, and prevents
      polyQ-mediated cell death of striatal neurons. Finally, we show that
      administration of FK506 to mice increases huntingtin S421 phosphorylation in
      brain. Collectively, these data highlight the importance of CaN in the modulation
      of S421 phosphorylation and suggest the potential use of CaN inhibition as a
      therapeutic approach to treat HD.

PMID- 16452688
TI  - Layer positioning of late-born cortical interneurons is dependent on Reelin but
      not p35 signaling.
AB  - We tested the response of interneurons to the absence of Reelin signaling or p35
      in the mouse neocortex. We provide three independent strands of evidence to
      demonstrate that layering of late-born (but not early-born) interneurons is
      regulated by Reelin signaling. First, early-born and late-born interneurons
      behaved differently in mice lacking Reelin or disabled 1 (Dab1). Early-born
      interneurons showed layer inversion, whereas late-born interneurons did not
      demonstrate layer inversion but were randomly distributed across the cortex.
      Second, in p35 mutant brains (in which Reelin signaling is intact), late-born
      interneurons are appropriately positioned in the upper layers despite the
      malpositioning of all other cortical neurons in these mice. Third, transplanted
      late-born interneuron precursors (wild type) into Dab1(-/-) cortices showed
      appropriate upper layer segregation. Together, these results indicate that, in
      the absence of Reelin signaling, late-born interneurons fail to laminate
      properly, and this is restored in an environment in which Reelin signaling is
      intact. These studies suggest different mechanisms for the stratification of
      cortical interneurons. Whereas the early-born interneurons appear to be
      associated with projection neuron layering, late-born interneurons rely on Reelin
      signaling for their correct lamination.

PMID- 16452689
TI  - Pharmaceutical policy issues for medical schools.

PMID- 16452691
TI  - Problem-solving skills for cognitive rehabilitation among persons with chronic
      psychotic disorders in Italy.
AB  - Studies have shown that teaching persons with mental illness to identify and cope
      with their real-life problems yields substantial clinical improvements. In Italy
      a structured problem-solving group was established in a day treatment center in
      2003. This column describes the approach and focuses on the outcomes achieved by
      15 patients with severe mental illness who were in this group. After completion
      of the problem-solving program, significant improvements were noted in symptom
      scores on the Positive and Negative Syndrome Scale and in problem-solving and
      neurocognitive test performance, with further improvements six months after
      completion of the group sessions. Problem-solving training may contribute to
      improved neurocognition and symptoms.

PMID- 16452692
TI  - Antidepressant medication use in private insurance health plans, 2002.

PMID- 16452693
TI  - Scaling Mount Rushmore: cartography of a manic episode.

PMID- 16452694
TI  - Relationship management therapy for patients with borderline personality
      disorder.
AB  - Relationship management therapy allows patients to choose their own treatment.
      The model requires that patients who engage in or threaten self-harm or
      aggressive behavior are discharged from the inpatient part of the program for 24
      hours. This study compared mean annual outcome rates for the 27 patients who were
      consecutively enrolled in the relationship management therapy program from 1998
      to 2000. Significant reductions were found in restraint, constant nursing
      observation, self-harm incidents, and inpatient days. These results fill a gap in
      the literature about a treatment model that one day could be considered a best
      practice.

PMID- 16452695
TI  - Comparison of ACT and standard case management for delivering integrated
      treatment for co-occurring disorders.
AB  - OBJECTIVE: Clients with co-occurring severe mental and substance use disorders
      are at high risk of institutionalization and other adverse outcomes. Although
      integrated mental health and substance abuse treatment is becoming a standard
      clinical approach for such clients, the optimal method for delivering integrated
      treatment remains unclear. METHOD: This study compared integrated treatment
      delivered within two different models of community-based case management
      (assertive community treatment and standard clinical case management). A total of
      198 clients in two urban sites who had co-occurring disorders and were homeless
      or unstably housed were randomly assigned to one of two treatment conditions and
      were followed for three years. RESULTS: Participants in both treatment conditions
      improved over time in multiple outcome domains, and few differences were found
      between the two models. Decreases in substance use were greater than would be
      expected given time alone. At the site that had higher rates of
      institutionalization, clients who received standard case management were more
      likely to be institutionalized. However, in the site that had lower rates of
      institutionalization, no differences in the rate of institutionalization were
      found between the two treatment conditions. CONCLUSIONS: Integrated treatment can
      be successfully delivered either by assertive community treatment or by standard
      clinical case management.

PMID- 16452696
TI  - Randomized trial of psychiatric care with representative payeeship for persons
      with serious mental illness.
AB  - OBJECTIVES: This randomized clinical trial assessed whether a community-based
      representative payee program that was coordinated with psychiatric care from the
      Department of Veterans Affairs was more effective than customary treatment.
      METHODS: In the experimental condition representative payeeship was provided by a
      community agency that worked to enroll clients and coordinate payeeship with
      clinical care through communication with clinical staff. The control condition
      consisted of customary clinical care that included the typical availability of
      representative payeeship. Hypotheses were that, compared with the control group,
      the experimental group would experience greater enrollment in a representative
      payee program; improved residential status; improved quality of life, including
      fewer symptoms of mental illness; less substance abuse; and improved money
      management. Participants were interviewed at baseline and at six and 12 months.
      Outcomes were analyzed with analysis of covariance by using covariates from the
      baseline. RESULTS: A total of 184 participants were enrolled at baseline (94 in
      the experimental group and 90 in the control group). A total of 152 interviews
      were completed at six months, and 149 were completed at 12 months. At 12 months,
      31 percent of patients in the experimental group and 14 percent of those in the
      control group were receiving representative payee services. At 12 months,
      significant positive effects were observed for the experimental group on
      enrollment in a representative payeeship, alcohol and drug use, quality of life,
      and money management. Residential status approached significance. CONCLUSIONS:
      Use of a coordinated representative payee program was found to be effective in
      improving outcomes at 12 months. Although this evidence supports the wider
      implementation of a coordinated representative payee program, only 31 percent of
      the experimental group had their money banked with a representative payee.
      Therefore, future studies should focus on achieving a better understanding of the
      causal components of the intervention.

PMID- 16452697
TI  - Awareness of illness and nonadherence to antipsychotic medications among persons
      with schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to assess the effects of patients'
      awareness of their illness on the clinical presentation, management, and course
      of nonadherence to antipsychotic medications among patients with schizophrenia.
      METHODS: A national survey was conducted of psychiatrists who were treating
      patients with schizophrenia. The survey was sent to 771 psychiatrists, of whom
      534 responded, for a response rate of 69 percent. The psychiatrists were asked to
      report on presentation, management, and course for one adult patient with
      schizophrenia who had been under their care for at least one year and who had
      been nonadherent to oral antipsychotics at some point in the past year. Patients
      who were aware that they had a mental illness were compared with those who were
      not aware. RESULTS: Of the 534 respondent psychiatrists, 310 reported on an
      eligible patient, and 300 of these patients were classified by illness awareness.
      Ninety-seven patients, or 32 percent, were not aware that they had a mental
      illness. These patients who lacked awareness had significantly longer episodes of
      antipsychotic nonadherence, were more likely to completely cease taking the
      antipsychotic medication, were more likely to have severe positive symptoms, and
      were more likely to be psychiatrically hospitalized after nonadherence than those
      who were aware of their illness. Psychological interventions and several types of
      family interventions were significantly less effective among patients who lacked
      awareness. CONCLUSIONS: A lack of awareness of mental illness is common among
      patients with schizophrenia who are nonadherent to antipsychotics. Such
      nonadherence tends to be especially disruptive and unresponsive to simple
      commonly used psychological interventions.

PMID- 16452698
TI  - A meta-analysis of labor supply effects of interventions for major depressive
      disorder.
AB  - OBJECTIVE: The aims of this study were to examine labor supply effects of
      interventions for major depressive disorder and to compare these effects with a
      summary measure of clinical effectiveness. METHODS: Research articles published
      in English-language journals from 1980 through May 2004 were searched by using
      five research databases. Only randomized trials that included a placebo group or
      a usual care group were eligible for the study, regardless of the specific type
      of intervention. Valid trials were those that enrolled adult patients with major
      depressive disorder and assessed changes in labor output by using a measure of
      time worked or labor market participation. From a total of 706 trials uncovered
      from the database searches, only four met all inclusion criteria. Trial outcomes
      were transformed into standardized effect sizes on the basis of Cohen's d.
      Hierarchical linear models were used to separately pool work outcomes and
      clinical outcomes. RESULTS: An improvement of .34 standard deviation was found in
      the size of the clinical effect of interventions compared with placebo or usual
      care among 1,261 unique patients with depression. An improvement of .12 standard
      deviation was found in the size of the effect on labor supply among 1,848 unique
      patients. CONCLUSIONS: Although the interventions studied were associated with
      reduced symptoms of depression and increased labor output, the labor benefits
      were small according to standard benchmarks used in interpreting the substantive
      significance of values of Cohen's d. The difference in effects may have been due
      to different underlying efficacies, brief durations of follow-up, or extrinsic
      factors that affect labor supply.

PMID- 16452699
TI  - Use of environmental supports among patients with schizophrenia.
AB  - OBJECTIVE: Cognitive adaptation training is a psychosocial treatment that uses
      individually tailored environmental supports, such as signs, calendars, hygiene
      supplies, and pill containers, to cue and sequence adaptive behavior in the
      client's home environment. Generic environmental supports offer a less costly
      treatment that provides a predetermined package of helpful supports to clients at
      the time of their routine clinic visit. Previous studies have demonstrated the
      efficacy of cognitive adaptation training. The study reported here examined the
      extent to which environmental supports are used by clients. METHODS: As part of
      an ongoing study, persons with schizophrenia were randomly assigned to one of
      three conditions: cognitive adaptation training, generic environmental supports,
      or assessment only. Rates of use of supports for the first three months of
      treatment were examined for the first 64 patients assigned to the first two
      groups. RESULTS: Rates of overall use averaged approximately 80 percent for
      cognitive adaptation training and 44 percent for generic environmental supports.
      Specific categories of supports were also significantly more likely to be used by
      patients who were receiving cognitive adaptation training. More than 66 percent
      of patients in cognitive adaptation training were classified as high users of
      supports (used more than 75 percent of supports provided appropriately), compared
      with only 13 percent of those who were receiving generic environmental supports.
      CONCLUSIONS: Environmental supports have been found to improve functional
      behaviors for patients with schizophrenia. However, supports are not likely to be
      used unless they are customized for individual clients and set up in the home
      environment.

PMID- 16452700
TI  - Predictors of physical functioning among adults with severe mental illness.
AB  - OBJECTIVES: Living conditions and treatment-related factors contribute to high
      rates of comorbid medical illness among adults with severe mental illness and
      undermine their physical well-being. This study examined physical functioning
      scores for this population and compared them with national norms. METHODS: A
      total of 309 residential care clients completed interviews. Diagnostic and
      sociodemographic variables were examined for significant associations with
      physical functioning, which was assessed with the Medical Outcomes Health Survey
      Short Form 36 (SF-36), and selected variables were entered into a hierarchical
      multiple regression analyses. Cross-sectional comparisons examined differences in
      scores between ten-year age groups in this sample and in the national data for
      men and women. RESULTS: In the final regression model, male gender, younger age,
      having earned income in the past six months, having less lifetime smoking, and
      having an admission diagnosis other than depression or schizophrenia spectrum
      disorders predicted better physical functioning. Functioning scores for the
      sample deviated from the national normed scores. Differences in functioning
      increased with each ten-year increment in age; study participants' functioning
      resembled that of cohorts ten to 20 years older. CONCLUSIONS: Determinants of
      physical functioning in this sample included well-known demographic predictors of
      health outcomes. The more striking finding was a deviation from normative data
      that began for study participants at the age of 25 years, indicating an early
      onset of limitations. The consistent trend of poorer functioning with each
      successive age group raises questions about the pace of physical decline among
      adults with mental illness that may be addressed in longitudinal studies.

PMID- 16452701
TI  - Crisis intervention team training for police officers responding to mental
      disturbance calls.
AB  - OBJECTIVES: In recognition of the fact that police are often the first responders
      for individuals who are experiencing a mental illness crisis, police departments
      nationally are incorporating specialized training for officers in collaboration
      with local mental health systems. This study examined police dispatch data before
      and after implementation of a crisis intervention team (CIT) program to assess
      the effect of the training on officers' disposition of calls. METHODS: The
      authors analyzed police dispatch logs for two years before and four years after
      implementation of the CIT program in Akron, Ohio, to determine monthly average
      rates of mental disturbance calls compared with the overall rate of calls to the
      police, disposition of mental disturbance calls by time and training, and the
      effects of techniques on voluntariness of disposition. RESULTS: Since the
      training program was implemented, there has been an increase in the number and
      proportion of calls involving possible mental illness, an increased rate of
      transport by CIT-trained officers of persons experiencing mental illness crises
      to emergency treatment facilities, an increase in transport on a voluntary
      status, and no significant changes in the rate of arrests by time or training.
      CONCLUSIONS: The results of this study suggest that a CIT partnership between the
      police department, the mental health system, consumers of services, and their
      family members can help in efforts to assist persons who are experiencing a
      mental illness crisis to gain access to the treatment system, where such
      individuals most often are best served.

PMID- 16452702
TI  - A survey of psychiatric residency directors on current priorities and preparation
      for public-sector care.
AB  - OBJECTIVE: This study assessed how resident psychiatrists are being prepared to
      deliver effective public-sector care. METHODS: Ten leaders in psychiatric
      education and practice were interviewed about which tasks they consider to be
      essential for effective public-sector care. The leaders identified 16 tasks.
      Directors of all general psychiatry residency programs in the United States were
      then surveyed to determine how they rate the importance of these tasks for
      delivery of care and how their training program prepares residents to perform
      each task. RESULTS: A total of 114 of 150 residency directors (76 percent)
      responded to the survey. Factor analysis divided 14 of the tasks into three
      categories characterized by the extent to which their performance requires
      integration of services: within the mental health system (for example, lead a
      multidisciplinary team), across social service systems (for example, interact
      with staff of supportive housing programs), and across institutions with
      different missions (for example, distinguish behavioral problems from underlying
      psychiatric disorders among prisoners). Preparation for tasks that involved
      integration of services across institutions was rated as least important, was
      least likely to be required, and was covered by less intensive teaching
      modalities. Tasks entailing integration within the mental health system were
      rated as most important, preparation was most likely to be required, and they
      were covered most intensively. Midway between these two categories, but
      significantly different from each, were tasks relying on integration across
      social service systems. CONCLUSIONS: Tasks that involved integrating services
      across institutions with different missions were consistently downplayed in
      training. Yet the importance of such tasks is underscored by the assessments of
      the psychiatric leaders who were interviewed, the high valuation placed on this
      type of integration by a substantial subset of training directors, and the extent
      of mental illness among populations who are institutionalized in nonpsychiatric
      settings.

PMID- 16452703
TI  - Mental distress among younger veterans before, during, and after the invasion of
      Iraq.
AB  - OBJECTIVE: The purpose of this study was to determine whether patients receiving
      care from the Department of Veterans Affairs (VA) reported more mental distress
      as the war in Iraq began or reintensified compared with other respondents to
      national health surveys. METHODS: Data from the 2000 and 2003 Behavioral Risk
      Factor Surveillance System (BRFSS) health surveys were analyzed. Unlike in other
      years, these particular surveys asked respondents whether they were military
      veterans. As in other years' surveys, these surveys also asked whether
      respondents used VA medical care. Male respondents were stratified by age and
      separated into three groups: VA patients, other veterans, and nonveterans. The
      proportions of respondents who reported five or more recent days of poor mental
      or physical health were analyzed with chi square tests. RESULTS: Although the
      number of recent days of poor mental health among nonveterans, other veterans,
      and older VA patients were stable from 2000 to 2003, younger VA patients in 2003
      reported substantially more days of poor mental health in two intervals: during
      the Iraq war buildup and invasion, and later, when resistance on the ground
      reintensified. Comparable changes in physical health complaints were not
      observed. CONCLUSIONS: In times of war, the VA may anticipate more mental health
      problems among its current patients, particularly younger veterans.

PMID- 16452704
TI  - The patient-oriented clinician-researcher: advantages and challenges of being a
      double agent.
AB  - The number of clinically trained individuals who perform research is declining.
      Although it is often observed that the clinician-researcher is necessary, the
      reasons are rarely discussed. In this article, the authors critically consider
      the complexities of the role of the patient-oriented clinician-researcher at the
      interface of behavioral health treatment and research. The authors note that
      patient-oriented clinician-researchers can serve as effective "bridgers" between
      the research and practice communities and can facilitate both the development of
      clinically relevant research and the dissemination of evidence-based treatments
      into routine clinical services. However, care needs to be taken to address the
      potential for ethical and role conflicts. Programs can encourage trainees to
      become clinician-researchers by providing opportunities for them to meet with
      patient-oriented clinician-researchers and by including coursework that raises
      their awareness of ethical and role conflicts and provides them with the skills
      needed to be effective "bridgers."

PMID- 16452706
TI  - Language and cultural barriers in the assessment of enemy prisoners of war and
      other foreign nationals.
AB  - The authors describe difficulties encountered in the assessment and treatment of
      enemy prisoners of war and foreign civilians during Operation Enduring Freedom
      and Operation Iraqi Freedom. Of prime concern was the complexity of evaluating
      and working with patients through translators. Secondary concerns included self
      protective behaviors of and fears experienced by patients, which complicated the
      patient-provider relationship. Future difficulties could be reduced by training
      translators in medical interviewing, training providers in the skills used by
      translators, informing providers of command and political policy, and producing
      concrete, portable information in written or other forms for enemy prisoners to
      reduce inherent mistrust.

PMID- 16452705
TI  - Prospective assessment of treatment use by patients with personality disorders.
AB  - OBJECTIVE: This study examined the utilization of mental health treatments over a
      three-year period among patients with schizotypal, borderline, avoidant, or
      obsessive-compulsive personality disorders compared with patients with major
      depressive disorder and no personality disorder. METHODS: A prospective,
      longitudinal study design was used to measure treatment use for 633 individuals
      aged 18 to 45 years during a three-year period. RESULTS: Patients with borderline
      personality disorder were significantly more likely than those with major
      depressive disorder to use most types of treatment. Furthermore, all patients
      continued using high-intensity, low-duration treatments throughout the study
      period, whereas individual psychotherapy attendance declined significantly after
      one year. CONCLUSIONS: Although our data showed that patients with borderline
      personality disorder used more mental health services than those with major
      depressive disorder, many questions remain about the adequacy of the treatment
      received by all patients with personality disorders.

PMID- 16452707
TI  - In-home psychosocial skills training for patients with schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to test an intervention that adapted the
      University of California, Los Angeles (UCLA) social and independent living skills
      program for application in the patient's home and in an outpatient setting in
      Spain. METHODS: An intervention group of 32 patients with schizophrenia was
      selected for comparison with a matched control group of patients who were
      undergoing conventional outpatient treatment for schizophrenia during six-month
      treatment periods. The Positive and Negative Syndrome Scale (PANSS) scoring
      system was used to compare the two groups, with a pretest-posttest design.
      RESULTS: Analysis of variance indicated a significant phase-by-treatment
      interaction effect of the intervention on PANSS scores. CONCLUSIONS: The results
      of this study suggest that a combination of outpatient follow-up care and in-home
      care centered on psychosocial skills training is more effective than conventional
      treatment in improving general symptoms among individuals with schizophrenia.

PMID- 16452708
TI  - Medicaid eligibility and access to mental health services among adolescents in
      substance abuse treatment.
AB  - OBJECTIVE: The co-occurrence of a mental disorder is common among adolescents who
      present for substance abuse treatment. This study was conducted to determine
      whether Medicaid eligibility was associated with greater use of mental health
      services. METHODS: The study used administrative data for 25,813 adolescents in
      Oregon. Propensity score analysis was used to assess the likelihood that the
      adolescents would use mental health services, with group differences and mental
      health need controlled for. RESULTS: Medicaid-eligible youths were nearly five
      times as likely to receive mental health services in the year they entered
      substance abuse treatment compared with non-Medicaid-eligible youths. In both
      groups, there was evidence of racial disparities as well as factors such as
      foster care that may facilitate access. CONCLUSIONS: The fact that Medicaid
      eligible youths have greater access to mental health services should be
      considered in both state policies and research design. States considering ways to
      better serve adolescents with co-occurring disorders would do well to examine
      ways to promote Medicaid enrollment or expand eligibility.

PMID- 16452709
TI  - Implementing psychoeducational interventions in Italy for patients with
      schizophrenia and their families.
AB  - OBJECTIVE: This study explored the feasibility of providing psychoeducational
      interventions for persons with schizophrenia and their families. METHODS: The
      study was carried out in 23 Italian mental health centers. Two professionals from
      each center attended three monthly training sessions on psychoeducational
      interventions. After the training, each professional provided informative
      sessions on schizophrenia to five families of service users with schizophrenia,
      which consisted of three meetings with each family on clinical aspects of
      schizophrenia, drug treatments, and detection of early signs of relapse. Each
      professional then provided the intervention to families for six months. RESULTS:
      Thirty-eight of the 46 participants completed the training course, and 34
      provided the intervention to 71 families. Twenty-nine of the 34 provided the
      entire intervention to the families and five of the 34 held only informative
      sessions on schizophrenia. Ninety-one percent of the participants who completed
      the study reported difficulties in integrating the intervention with their other
      work responsibilities, and 96 percent acknowledged the positive effect that the
      intervention had on the center's relationship with patients with schizophrenia
      and their families. CONCLUSIONS: These results support the idea that it is
      possible to introduce psychoeducational interventions in mental health services
      after a relatively brief period of training and supervision.

PMID- 16452710
TI  - Representation of asylum seekers and refugees among psychiatric inpatients in
      London.
AB  - OBJECTIVE: Refugees are at high risk of mental disorders but often complain about
      a lack of access to appropriate care. The purpose of this study was to assess the
      representation of refugees among psychiatric inpatients, given that it has been
      suggested that they use a disproportionate level of care compared with
      nonrefugees. METHODS: A census of all psychiatric inpatient units in London was
      used to determine the numbers of inpatients, the numbers of refugees, and
      measures of need, such as compulsory detention, duration of admission, need for
      interpreters, and whether inpatient status was appropriate. RESULTS: Of 2,955
      psychiatric inpatients, 134 (4.5 percent) were refugees. Refugees' admission
      rates were similar to or lower than those of nonrefugees. Refugees were more
      likely to be inappropriately placed, to require interpreters, and to have more
      complex needs. CONCLUSION: The results of this study suggest that refugees are
      not overusing London's psychiatric inpatient units but have complex needs that
      challenge existing service providers.

PMID- 16452711
TI  - Eviction as a risk factor for suicide.

PMID- 16452713
TI  - Pay-for-performance initiatives and B. F. Skinner.

PMID- 16452714
TI  - Regulation of dynamic events by microfilaments during oocyte maturation and
      fertilization.
AB  - Actin filaments (microfilaments) regulate various dynamic events during oocyte
      meiotic maturation and fertilization. In most species, microfilaments are not
      required for germinal vesicle breakdown and meiotic spindle formation, but they
      mediate peripheral nucleus (chromosome) migration, cortical spindle anchorage,
      homologous chromosome separation, cortex development/maintenance, polarity
      establishment, and first polar body emission during oocyte maturation. Peripheral
      cortical granule migration is controlled by microfilaments, while mitochondria
      movement is mediated by microtubules. During fertilization, microfilaments are
      involved in sperm incorporation, spindle rotation (mouse), cortical granule
      exocytosis, second polar body emission and cleavage ring formation, but are not
      required for pronuclear apposition (except for the mouse). Many of the events are
      driven by the dynamic interactions between myosin and actin filaments whose
      polymerization is regulated by RhoA, Cdc42, Arp2/3 and other signaling molecules.
      Studies have also shown that oocyte cortex organization and polarity formation
      mediated by actin filaments are regulated by mitogen-activated protein kinase,
      myosin light-chain kinase, protein kinase C and its substrate p-MARKS as well as
      PAR proteins. The completion of several dynamic events, including homologous
      chromosome separation, spindle anchorage, spindle rotation, vesicle organelle
      transport and pronuclear apposition (mouse), requires interactions between
      microfilaments and microtubules, but determination of how the two systems of the
      cytoskeleton precisely cross-link, and which proteins link microfilaments to
      microtubules to perform functions in eggs, requires further studies. Finally, the
      meaning of microfilament-mediated oocyte polarity versus embryo polarity and
      embryo development in different species (Drosophila, Xenopus and mouse) is
      discussed.

PMID- 16452715
TI  - Deconstructing mammalian reproduction: using knockouts to define fertility
      pathways.
AB  - Reproduction is the sine qua non for the propagation of species and continuation
      of life. It is a complex biological process that is regulated by multiple factors
      during the reproductive life of an organism. Over the past decade, the molecular
      mechanisms regulating reproduction in mammals have been rapidly unraveled by the
      study of a vast number of mouse gene knockouts with impaired fertility. The use
      of reverse genetics to generate null mutants in mice through targeted disruption
      of specific genes has enabled researchers to identify essential regulators of
      spermatogenesis and oogenesis in vivo and model human disorders affecting
      reproduction. This review focuses on the merits, utility, and the variations of
      the knockout technology in studies of reproduction in mammals.

PMID- 16452716
TI  - Association between myristoylated alanin-rich C kinase substrate (MARCKS)
      translocation and cortical granule exocytosis in rat eggs.
AB  - Cortical granule exocytosis (CGE), following egg activation, is a secretory
      process that blocks polyspermy and enables successful embryonic development. CGE
      can be triggered independently by either a rise in intracellular calcium
      concentration ([Ca2+]i) or activation of protein kinase C (PKC). The present
      study investigates the signal transduction pathways leading to CGE through
      activation of PKC or stimulation of a rise in [Ca2+]i. Using Western blot
      analysis, co-immunoprecipitation and immunohistochemistry, combined with various
      inhibitors or activators, we investigated the link between myristoylated alanin
      rich C kinase substrate (MARCKS) translocation and CGE. We were able to
      demonstrate translocation of MARCKS from the plasma membrane to the cortex, in
      fertilized as well as in parthenogenetically activated eggs. MARCKS
      phosphorylation was demonstrated upon PKC activation, whereas a PKC inhibitor
      (myrPKCpsi) prevented both MARCKS translocation and CGE in 12-O-tetradecanoyl
      phorbol-13-acetate (TPA)-activated eggs. We have further shown that upon egg
      activation the amount of phosphorylated MARCKS (p-MARCKS) and the amount of
      calmodulin bound to MARCKS were increased. MARCKS translocation in ionomycin
      activated eggs was also inhibited by the calmodulin inhibitor N-(6-aminohexyl)-5
      chloro-1-napthalenesulfonamide hydrochloride (W7). These results complement other
      studies showing MARCKS requirement for exocytosis and imply that upon
      fertilization, MARCKS translocation is followed by CGE. These findings present a
      significant contribution to our understanding of CGE in mammalian eggs in
      particular, as well as cellular exocytosis in general.

PMID- 16452717
TI  - Mitochondria directly influence fertilisation outcome in the pig.
AB  - The mitochondrion is explicitly involved in cytoplasmic regulation and is the
      cell's major generator of ATP. Our aim was to determine whether mitochondria
      alone could influence fertilisation outcome. In vitro, oocyte competence can be
      assessed through the presence of glucose-6-phosphate dehydrogenase (G6PD) as
      indicated by the dye, brilliant cresyl blue (BCB). Using porcine in vitro
      fertilisation (IVF), we have assessed oocyte maturation, cytoplasmic volume,
      fertilisation outcome, mitochondrial number as determined by mtDNA copy number,
      and whether mitochondria are uniformly distributed between blastomeres of each
      embryo. After staining with BCB, we observed a significant difference in
      cytoplasmic volume between BCB positive (BCB+) and BCB negative (BCB-) oocytes.
      There was also a significant difference in mtDNA copy number between fertilised
      and unfertilised oocytes and unequal mitochondrial segregation between
      blastomeres during early cleavage stages. Furthermore, we have supplemented BCB-
      oocytes with mitochondria from maternal relatives and observed a significant
      difference in fertilisation outcomes following both IVF and intracytoplasmic
      sperm injection (ICSI) between supplemented, sham-injected and non-treated BCB-
      oocytes. We have therefore demonstrated a relationship between oocyte maturity,
      cytoplasmic volume, and fertilisation outcome and mitochondrial content. These
      data suggest that mitochondrial number is important for fertilisation outcome and
      embryonic development. Furthermore, a mitochondrial pre-fertilisation threshold
      may ensure that, as mitochondria are diluted out during post-fertilisation
      cleavage, there are sufficient copies of mtDNA per blastomere to allow
      transmission of mtDNA to each cell of the post-implantation embryo after the
      initiation of mtDNA replication during the early postimplantation stages.

PMID- 16452718
TI  - Body composition, dietary carbohydrates and fatty acids determine post
      fertilisation development of bovine oocytes in vitro.
AB  - This study assessed the interactive effects of carbohydrate type (fibre vs
      starch) and fatty acid (FA) supplementation (0% vs 6% calcium soaps of palm oil
      FA) on the post-fertilisation development of oocytes recovered from low and
      moderate body condition score (BCS) heifers. A secondary objective was to compare
      the FA composition of plasma to that of granulosa cells (GCs) and cumulus-oocyte
      complexes (COCs) from these animals, and to relate these findings to the
      developmental potential of oocytes. Plasma, GCs and COCs were recovered from 32
      heifers on day 5 of a synchronised oestrous cycle for FA analyses. Oocytes were
      also recovered on days 10 and 15 of the same cycle after short-term ovarian
      stimulation (FSH + GnRH), and matured, fertilised and cultured to the blastocyst
      stage in vitro. High levels of dietary starch increased (P < 0.01) plasma insulin
      but, together with dietary FA, reduced (P < 0.05) blastocyst yields in low, but
      not in moderate, BCS heifers. Diet-induced alterations to the FA content of
      plasma were less apparent in GCs and COCs. In summary, although dietary lipids
      increased the FA content of COCs, the selective uptake of saturated FAs at the
      expense of mainly polyunsaturated FAs within the follicular compartment ensured
      that the FA composition of COCs was largely unaffected by diet. However, the
      concentration of saturated FAs within COCs was inherently high, and so further
      increases in FA content may have impaired post-fertilisation development. The
      data establish a robust nutritional framework for more detailed studies into the
      mechanistic effects of dietary composition on the post-fertilisation
      developmental potential of oocytes.

PMID- 16452719
TI  - The employment of strontium to activate mouse oocytes: effects on spermatid
      injection outcome.
AB  - The present research investigated the effects of various strontium
      concentrations, in combination with different incubation periods, on mouse
      parthenogentic oocyte activation and blastocyst development. The results for
      blastocyst development showed a trend indicating that 10 mM strontium for 3 h was
      the optimal strontium protocol. Ethanol, an agent that incites oocyte activation
      via a monotonic rise in calcium, was employed as a control. The outcome of
      blastocyst formation arising from parthenogenic ethanol activation was
      significantly less (P < 0.001) than that achieved by the optimal strontium
      protocol. To assess the impact of strontium oocyte activation on embryo viability
      following fertilization with immature germ cells, the protocol of 10 mM strontium
      for 3 h was applied to oocytes injected with round spermatids and then compared
      with other protocols. The results indicate that following round-spermatid
      injection the benefits derived from strontium artificial oocyte activation are
      evident during both pre- and post-implantation development. However, in order to
      adjust the protocol to the most effective round-spermatid injection in relation
      to the oocyte cell cycle, injection was done 1.5 h after strontium activation
      followed by another 1.5 h activation in strontium. The implementation of round
      spermatid injection in combination with this oocyte-activation protocol led to
      live-birth outcomes not significantly different to those outcomes obtained by
      mature spermatozoa.

PMID- 16452720
TI  - The effect of paracrine/autocrine interactions on the in vitro culture of bovine
      preimplantation embryos.
AB  - Bovine preimplantation embryos develop more successfully when cultured in groups,
      proibably because of the increased production of, and exposure to, embryotrophic
      autocrine and paracrine factors. Using a novel embryo culture technique, this
      study had two aims: 1. to determine the distance over which potential paracrine
      interactions affect bovine embryo development in terms of blastocyst and hatching
      rates, cell counts and carbohydrate metabolism; 2. to investigate the effect of
      platelet-activating factor (PAF) supplementation on bovine embryo development and
      metabolism. Groups of 16 presumptive zygotes were attached to the bottom of a
      culture dish by the cell adhesive Cell-Tak in a 4 x 4 equidistant array. The
      distance between individual embryos in each group was 0-689 microm. Optimal
      blastocyst formation rate occurred when embryos were cultured 165 microm apart
      compared with control non-attached zygotes (Kruskal-Wallis followed by Mann
      Whitney U test post-hoc; P < 0.05). Increasing the distance between embryos
      resulted in a further decline in blastocyst rate, which reached zero at 540
      microm apart. Blastocyst cell number, pyruvate/glucose uptake and lactate
      production decreased as the interembryo distance increased from 240 to 465 microm
      (P < 0.05). Supplementation with PAF during conventional group culture enhanced
      blastocyst cell number, hatching rates and the oxidative metabolism of pyruvate
      and glucose. The data indicate that the distance between individual bovine
      embryos in culture influences preimplantation development, in particular
      blastocyst formation, cell number and metabolism. It is suggested that diffusible
      paracrine/autocrine factors, such as PAF, are in part responsible for the
      regulation of early embryo development.

PMID- 16452721
TI  - Effects of gonadotrophin treatments on meiotic and developmental competence of
      oocytes in porcine primordial follicles following xenografting to nude mice.
AB  - Our objective was to improve the developmental ability of oocytes in porcine
      primordial follicles xenografted to nude mice, by treating the host mice with
      gonadotrophins to accelerate follicular growth. Ovarian tissues from 20-day-old
      piglets, in which most of the follicles were primordial, were transplanted under
      the kidney capsules of ovariectomized nude mice. Gonadotrophin treatments were
      commenced around 60 days after vaginal cornification in the mice. Ovarian grafts
      were obtained 2 or 3 days after treatment with equine chorionic gonadotrophin
      (eCG-2 and eCG-3 groups), after porcine FSH infusion for 7 or 14 days, or after
      infusion of porcine FSH for 14 days with a single injection of estradiol
      antiserum (FSH-7, FSH-14 and FSH-14EA groups, respectively). Gonadotrophin
      treatments accelerated follicular growth within the xenografts compared with that
      in control mice given no gonadotrophins, consistent with higher (P < 0.05)
      circulating inhibin levels in the gonadotrophin-treated mice. In contrast,
      circulating mouse FSH levels were significantly (P < 0.05) depressed. We
      recovered large numbers of full-sized oocytes with meiotic competence to the
      mature stage from the eCG-3, FSH-7, and FSH-14EA, unlike in the control group.
      Moreover, 56% of matured oocytes with the first polar body (n = 39) were
      fertilized in vitro in the FSH-14EA group. After in vitro fertilization and
      subsequent culture for 7 days, one blastocyst was obtained from each of the eCG
      3, FSH-7 and, FSH-14EA groups, whereas no blastocysts appeared in the other
      groups. Exogenous gonadotrophins--not mouse FSH--stimulated the growing follicles
      that had developed from the primordial follicles in the xenografts: the effects
      were incomplete but improved to some extent the meiotic and developmental
      abilities of the oocytes.

PMID- 16452722
TI  - Chemical manipulation of glucose metabolism in porcine oocytes: effects on
      nuclear and cytoplasmic maturation in vitro.
AB  - The objectives of this study were to manipulate metabolism of glucose through
      glycolysis and the pentose phosphate pathway (PPP) in porcine oocytes during in
      vitro maturation, and determine the effects of this manipulation on meiotic
      progression, intracellular glutathione (GSX) concentrations and embryonic
      development. Cumulus-oocyte complexes isolated from abattoir ovaries were matured
      (40-44 h) in Purdue Porcine Medium for maturation alone (control) or supplemented
      with pyrroline-5 carboxylate (PC, 0.1 microM; PPP stimulator),
      diphenyleneiodonium (DPI, 0.1 microM; PPP inhibitor), dinitrophenol (DNP, 10
      microM; glycolytic stimulator), hexametaphosphate (HMP, 100 microM; glycolytic
      inhibitor), PC + HMP or DNP + DPI. At the conclusion of in vitro maturation,
      cumulus cells were removed and oocytes were randomly allocated for analysis of
      GSX, metabolism and nuclear maturation, or in vitro fertilization and embryo
      culture. Both DPI and DNP + DPI decreased (P < or = 0.05) the activity of
      glycolysis and the PPP, increased (P < or = 0.05) the percentage of immature
      oocytes, and decreased (P < or = 0.05) the proportion of mature oocytes compared
      with control oocytes and oocytes from the other treatments. Embryonic development
      (cleavage and blastocyst stage) and the intracellular content of GSX were also
      decreased (P < or = 0.05) following exposure to DPI or DNP + DPI compared with
      control oocytes and oocytes from the other treatments. Oocyte metabolism, nuclear
      maturation, GSX content and embryonic development were unaffected (P > 0.05)
      following exposure to PC, DNP, HMP or PC + HMP. Our results suggest that
      metabolism of glucose through the PPP and/or glycolysis plays a key role in the
      control of nuclear and cytoplasmic maturation of porcine oocytes in vitro.

PMID- 16452723
TI  - Rapid effects of pesticides on human granulosa-lutein cells.
AB  - Following our previous demonstration that p,p'-DDE
      (dichlorodiphenylchloroethylene), at environmentally relevant concentrations, can
      rapidly increase intracellular calcium [Ca2+]i concentrations in human granulosa
      lutein cells, we examined whether other pesticides, such as Kepone, o,p-DDE and
      methoxychlor, have similar effects. Cultured human granulosa-lutein cells were
      loaded with Fura-2 AM, and changes in [Ca2+]i concentrations within small areas
      of single cells were studied with a dynamic digital Ca2+ imaging system. Kepone,
      at concentrations of 0.2-2 nmol/ml, consistently increased [Ca2+]i concentrations
      2-6 times higher than baseline values within minutes of exposure. Methoxychlor at
      concentrations of 2.8-280 nmol/ml failed to alter [Ca2+]i levels consistently in
      cells from 10 patients. However, at 0.28 and 1.4 nmol/ml, increases in [Ca2+]i
      concentrations could be elicited by methoxychlor. The isomer o,p-DDE at 3 nmol/ml
      increased [Ca2+]i in granulosa cells of 11/20 patients. Pertussis toxin treatment
      inhibited the [Ca2+]i increases induced by estradiol, p,p'-DDE, o,p-DDE and
      methoxychlor, but not by Kepone or progesterone, indicating that Kepone and
      progesterone may act through an insensitive G protein-coupled receptor. The
      [Ca2+]i increases induced by Kepone also occurred in Ca2+-free medium, suggesting
      that [Ca2+]i mobilization occurred from the smooth endoplasmic reticulum.
      Thapsigargin and cyclopiazonic acid, two inhibitors of the endoplasmic reticulum
      Ca2+ pump, also stimulated [Ca2+]i increases but did not inhibit the Ca2+
      response to all the pesticides. These results demonstrate that pesticides can
      have a rapid effect on human granulosa-lutein cells, and a nongenomic mechanism
      of action is suggested.

PMID- 16452724
TI  - Binding of boar spermatozoa to oviductal epithelium in vitro in relation to sperm
      morphology and storage time.
AB  - In vitro short-term storage of boar semen for up to 72 h before insemination
      negatively affects fertility, but this often remains undetected during semen
      quality assessment. One important sperm function is the ability to form the
      functional sperm reservoir in the oviduct. In the present study, we used the
      modified oviductal explant assay to study sperm binding to oviductal epithelium
      in vitro in diluted boar semen stored for 24 or 72 h. First, we determined the
      kinetics of in vitro sperm binding to oviductal epithelium in relation to co
      incubation time of sperm and oviductal tissue pieces. Then, we studied how the
      binding of sperm to oviductal epithelium was affected by in vitro semen storage
      and by differences among individual boars. Sperm binding after different
      incubation times was significantly higher when semen was stored 24 h than after
      72-h storage (P < 0.05), and peaked at 30-90 min of incubation. Sperm binding
      differed between boars (n = 44), and was negatively correlated to the percentage
      of sperm with cytoplasmic droplets (R = -0.51, P < 0.001). There were no
      significant changes in motility, acrosome integrity and propidium iodide
      stainability during the 72-h storage period. However, sperm-binding indices were
      significantly lower after 72 h in vitro storage than after 24-h storage in sperm
      from boars with normal semen quality (P < 0.05); in contrast, the binding
      capacity of sperm from boars with higher percentages of morphologically altered
      sperm remained at a low level. The sperm-binding capacity of sperm from four of
      the five boars with known subfertility was lower than the mean binding index
      minus one standard deviation of the boar population studied here. It is concluded
      that changes in the plasma membrane associated with in vitro ageing reduce the
      ability of stored boar sperm to bind to the oviductal epithelium. This study
      shows the potential of sperm-oviduct binding as a tool to assess both male
      fertility and changes in sperm function associated with in vitro ageing.

PMID- 16452726
TI  - Remodeling and angiotensin II responses of the uterine arcuate arteries of
      pregnant rats are altered by low- and high-sodium intake.
AB  - Lowering and increasing sodium intake in pregnant rats evoke opposite changes in
      renin-angiotensin-aldosterone system (RAAS) activity and are associated with
      alterations of blood volume expansion. As augmented uterine blood flow during
      gestation is linked to increased circulatory volume, we wanted to determine if
      low- and high-sodium intakes affect the mechanical properties and angiotensin II
      (AngII) responses of the uterine vasculature. Non-pregnant and pregnant rats
      received a normal sodium (0.22% Na+) diet. On the 15th day of gestation some
      animals were moved to a low-sodium (0.03%) diet, whereas others were given NaCl
      supplementation as beverage (saline, 0.9% or 1.8%) for 7 days. All rats were
      killed after 7 days of treatment (eve of parturition). Uterine arcuate arteries
      (>100 microm) were set up in wire myographs under a tension equivalent to 50 mmHg
      transmural pressure. The pregnancy-associated increase in diameter of the uterine
      arteries was significantly attenuated on the low-sodium diet and 1.8% NaCl
      supplementation. The arcuate arteries of non-pregnant rats on the low-sodium diet
      showed markedly increased responses to AngII and phenylephrine (Phe). Pregnancy
      also resulted in heightened responses to AngII and Phe that were significantly
      reduced for the former agent in rats on the low-sodium diet. Sodium
      supplementation of non-pregnant rats did not affect the reactivity of the uterine
      arteries to AngII, but significantly reduced the effect of Phe (1 micromol/l).
      High salt also significantly diminished the elevated responses to AngII in the
      arteries of pregnant animals. It was observed that altered sodium intake affects
      the mechanical and reactive properties of the uterine arcuate arteries more
      importantly in pregnant than in non-pregnant rats. Low-salt intake similarly
      affected the reactivity of the uterine arcuate arteries to AngII and Phe, whereas
      high-salt intake more specifically affected AngII responses. These results showed
      that perturbations of sodium intake have major impacts on the structure and
      functions of the uterine arterial circulation, indicating RAAS involvement in
      uterine vascular remodeling and function during gestation.

PMID- 16452725
TI  - Changes in fibroblast growth factor 2 and its receptors in bovine follicles
      before and after GnRH application and after ovulation.
AB  - The aim of this study was to evaluate the expression pattern of fibroblast growth
      factor 2 (FGF2), its receptor variants (FGFR1IIIc, FGFR2IIIc) and nucleolin in
      time-defined follicle classes before and after GnRH application and after
      ovulation in the cow. Ovaries containing preovulatory follicles or new corpora
      lutea (CL) were collected at approximately 0, 4, 10, 20 and 25 h (follicles) and
      60 h (new CL) relative to injection of GnRH to induce an LH surge (n = 5 animals
      per group). The expressions of FGF2 and FGFR1IIIc mRNA were significantly up
      regulated only in the follicle group 4 h after GnRH (during the LH surge) with a
      significant down-regulation immediately afterwards. Western blot analyses showed
      two protein bands with at 22 and 18 kDa with apparent up-regulation beginning
      with the LH surge (4 h) and maximum levels 20 h after GnRH. FGF2 protein in
      follicles collected at 0 h (before LH surge) was localised in theca tissue
      (endothelial and pericytes of blood vessels) but not in granulosa cells (GCs).
      The FGF2 staining (by immunohistochemistry) pattern changed dramatically after
      the LH surge for a short period (about 2 days) and FGF2 protein was localised
      dominantly in the nucleus of many GCs, while most capillary endothelial cells
      were FGF2 immunonegative. In conclusion, the novel observation of FGF2 up
      regulation and the distinct change in FGF2 localisation from theca (cytoplasm of
      endothelial cells) to the nucleus of GCs after the LH surge may be important for
      survival of GCs or for the transition of the GCs to luteal cells.

PMID- 16452727
TI  - Evidence for heterodimeric association of leukemia inhibitory factor (LIF)
      receptor and gp130 in the mouse uterus for LIF signaling during blastocyst
      implantation.
AB  - Implantation failure in mice lacking leukemia inhibitory factor (LIF) establishes
      that this cytokine is crucial to this process. LIF transcripts are expressed in
      the uterus in a biphasic manner: LIF is expressed in the gland on the morning of
      day 4 and again in stromal cells surrounding the blastocyst with the onset of
      implantation in the evening of day 4 of pregnancy. However, it is not yet clear
      whether both phases of LIF expression are required for implantation, since the
      receptor usage by uterine LIF still remains elusive. Here we have provided
      evidence that major cell types expressing theLIF receptor (LIFR) and its signal
      transducing partner gp130 are mostly disparate in the mouse uterus during the
      glandular LIF expression in the morning of day 4. In contrast, LIFR and gp130
      expressions overlap in the luminal epithelium at the time of blastocyst
      attachment on the evening of day 4 when the second phase of LIF expression occurs
      in stromal cells surrounding the blastocyst, suggesting that LIF participates in
      implantation in a paracrine manner. Similar expression patterns for LIFR and
      gp130 were observed when a delayed implantation model was used. For example, a
      transient overlapping expression of LIFR and gp130 was evident at 12 h after
      estrogen-induced termination of delayed implantation. Coimmunoprecipitation
      experiments showed that LIFR and gp130 form heterodimers and are available for
      LIF signaling at the time of blastocyst attachment. We have also shown that an
      intra-peritoneal administration of recombinant LIF in LIF-deficient pregnant mice
      on the evening of day 4, close to the time when the second phase of LIF
      expression is normally observed, is sufficient to rescue implantation failure,
      and that there is no evidence of antagonistic action by soluble forms of the
      receptors. Collectively, our results have provided evidence that LIFR and gp130
      form a functional heterodimer in the uterus during the attachment reaction to
      direct LIF signaling.

PMID- 16452728
TI  - Changes in vascular leakage and expression of angiopoietins in the corpus luteum
      during pregnancy in rats.
AB  - The present study investigates changes in blood vessel stability and its
      regulation in the corpus luteum (CL) during pregnancy in the rat. First, blood
      vessel stability in the CL was evaluated during pregnancy based on vascular
      leakage, which was quantified by the Evans blue assay. Vascular leakage was
      highest on day 3, thereafter decreased until day 15 and increased again on day
      21. Secondly, to study the regulation of vascular leakage, the expression of
      angiopoietins was examined in the CL during pregnancy. Angiopoietin-1 (Ang-1)
      effects maturation and stabilization of newly formed blood vessels, while Ang-2
      produces the opposite effect by allowing vascular remodeling. An
      immunohistochemical study showed both Ang-1 and Ang-2 expression in luteal cells.
      mRNA and protein levels of Ang-1 were significantly higher on days 12 and 15 than
      those on days 3 and 21, whereas there was no significant change in Ang-2
      expression. Since estradiol contributes to CL development during mid-pregnancy,
      we finally studied whether estradiol regulates vascular leakage and angiopoietin
      expression. Rats undergoing hypophysectomy and hysterectomy (hypox-hect) on day
      12 were treated with estradiol until day 15. Vascular leakage was increased and
      Ang-1 expression was decreased by hypox-hect, and these effects were completely
      reversed by estradiol treatment. In conclusion, blood vessel stability in the CL
      is likely to be associated with CL development and CL regression, and may be
      regulated by angiopoietins. Estradiol contributes to blood vessel stabilization
      in the CL during mid-pregnancy, which is associated with an increase in Ang-1
      expression.

PMID- 16452729
TI  - Involvement of the coeliac ganglion in the luteotrophic effect of androstenedione
      in late pregnant rats.
AB  - Using the ex vivo coeliac ganglion-superior ovarian nerve-ovary system at the end
      of pregnancy when luteal regression starts, we investigated whether, when
      administered systemically or when added directly to the ganglion compartment,
      androstenedione (A2) can reverse such regression, and whether the neural
      (noradrenaline (NA)) and endocrine (A2) joint action modifies the release of
      ovarian progesterone. The experimental groups were as follows: group 1--A2
      injected systemically 48 h before incubation of the system (A2)s; group 2--A2
      directly added to the ganglion compartment (A2)g; group 3--A2 injected 48 h
      before incubation of the system with NA in the ganglion compartment (A2 + NA);
      group 4--A2 plus NA added to the ganglion compartment (NA + A2)g. The controls
      were ex vivo systems without treatment (control), and with the addition of NA
      alone in the ganglion compartment (NA). The results were as follows. For (A2s)
      versus control, progesterone increased on days 19 and 21 of pregnancy at all the
      studied times and only at 180 min on day 20. For (A2 + NA) versus (A2)s,
      progesterone increased on days 19 and 21. For (A2 + NA) versus NA, progesterone
      increased at all the studied times on days 19 and 21 and at 180 min on day 20.
      For (A2)g versus control, progesterone significantly increased every pregnancy
      day. For (NA + A2)g versus (A2)g, progesterone decreased at 120 and 180 min on
      day 19. For (NA + A2)g versus NA, progesterone increased on days 20 and 21. We
      can conclude that A2 can reverse the functional regression of the corpus luteum
      either systemically or, what is more surprising, when directly added to the
      coeliac ganglion, whose action on the ovary is exerted via superior ovarian
      nerve.

PMID- 16452730
TI  - Redistribution of aquaporins 1 and 5 in the rat uterus is dependent on
      progesterone: a study with light and electron microscopy.
AB  - During early pregnancy in the rat there is a dramatic reduction in luminal fluid
      which is associated with uterine receptivity for blastocyst implantation. This
      study investigates the presence and distributional changes of several members of
      the aquaporin (AQP) family in the rat uterus in response to hormonal regime. An
      increase in apical AQP5 protein expression was found in response to progesterone
      alone or in combination with oestrogen, which is similar to that seen at the time
      of implantation. AQP1 was found in endothelial cells of the endometrium and in
      the inner circular layer of smooth muscle, with maximal protein expression seen
      after three doses of progesterone plus 8 hr of oestrogen treatment. These
      results, for the first time, show that the up-regulation of AQP5 in the apical
      plasma membrane of uterine epithelial cells and AQP1 in the inner circular layer
      of myometrium, is dependent on progesterone. Furthermore, unlike during normal
      pregnancy, there is no differential gradient of AQP5 expression between
      mesometrial and antimesometrial poles of the progesterone treated uterus. Hence
      it is suggested that the differential gradient of AQP5 is dependent on the
      presence of a blastocyst, in addition to the appropriate hormonal environment.

PMID- 16452731
TI  - Global characterization of porcine intrauterine proteins during early pregnancy.
AB  - Total protein secreted in the intrauterine lumen increases between day 10 and 13
      post-estrus in both cyclic and pregnant gilts. The objective of this experiment
      was to identify those intrauterine proteins whose secretion changes during this
      time period. Sixteen mature gilts were either mated (day 0) or remained cyclic
      and were slaughtered at either day 10 or day 13 (n = 4 per status by day). At
      slaughter, each uterine horn was flushed with 20 ml Minimal Essential Medium.
      Flushings were dialyzed extensively against distilled water. A 0.5 ml aliquot of
      each was lyophilized, subjected to two-dimensional PAGE, and protein spots were
      identified following Coomassie staining of each gel. Densitometry was used to
      compare relative amounts of each spot. After statistical analysis, spots that
      differed due to either day, status, or day by status interaction were excised and
      digested in-gel with trypsin. The resulting peptides were analyzed by tandem mass
      spectrometry (MS/MS). Using MS/MS data, protein identification for each spot was
      attempted. There were 280 matching spots, of which 132 were significantly (P <
      0.05 or 0.01) affected by pregnancy status, day, or the day by status
      interaction. Most (73%) spots increased from day 10 to day 13 with no effect of
      pregnancy. Several spots were identified as proteases or their inhibitors. Others
      potentially modify glycolipids and/or glycoproteins. These results indicate that
      the concentrations of many proteins within the intrauterine environment during
      early pregnancy are independent of the conceptus and could play roles in
      regulating the endometrial or conceptus glycocalyx.

PMID- 16452732
TI  - Parents' concerns regarding their ART children.
AB  - A cohort of children conceived by assisted reproductive therapy (ART)--in vitro
      fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) has been
      followed up in a National Child Development Study (Sutcliffe et al. 1999, 2001
      and Bonduelle et al. 2005). Their parents were contacted and asked questions
      designed to elicit any concerns on their part about their child. 329 replies were
      received (90% response rate), and 86 of the families posed additional questions.
      We found that a small number of parents (26% of respondents) raised questions
      about a variety of issues regarding their ART-conceived child. The most commonly
      expressed theme (8% of all respondents, or 27/86 (31%) of the respondents with
      questions) pertained to their child's future fertility. This question was asked
      more frequently by ICSI than IVF parents.

PMID- 16452733
TI  - Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in
      homocysteine concentrations in women with idiopathic recurrent pregnancy losses.
AB  - Because they have been described as strong risk factors for idiopathic recurrent
      pregnancy losses (RPLs), we assessed the association between the
      methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms
      (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with
      idiopathic RPL. Study subjects comprised 200 patients with more than three
      consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs
      were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured
      with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs
      4.0%) genotypes was significantly higher in patients. While it was similar among
      patients and controls (P = 0.095), higher homocysteine was seen with the T/T (but
      not 1298A/C and 1298C/C) genotype among patients and controls compared with non
      T/T carriers (P < 0.05), and in patients vs controls. Higher prevalence of MTHFR
      677T/T was seen in late (P < 0.05) and early-late (P < 0.001) RPL, while higher
      prevalence of 1298C/C genotype was seen only in early-late RPL (P < 0.001), and
      the prevalence of double heterozygotes was statistically not significant between
      patients and controls (P = 0.10; odds ratio = 2.73). Logistic regression analysis
      showed that, after adjusting for all variables, homozygosity for MTHFR C677T was
      associated with late (P < 0.001), and combined early-late (P < 0.001), while
      homozygosity for A1298C was associated only with combined early-late (P = 0.026),
      as was secondary-level education, which was associated with early (P = 0.005),
      late (P = 0.026) and combined early-late (P = 0.004) abortions. Homozygosity for
      MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for
      RPLs, irrespectively of total homocysteine levels.

PMID- 16452734
TI  - Randomized comparison of reduction and fixation, bipolar hemiarthroplasty, and
      total hip arthroplasty. Treatment of displaced intracapsular hip fractures in
      healthy older patients.
AB  - BACKGROUND: Orthopaedic surgeons vary in their management of displaced
      intracapsular fractures of the hip in healthy older patients. The aim of this
      investigation was to determine the functional, clinical, and resource
      consequences of three different types of surgical treatment. METHODS: The study
      was a multicenter randomized controlled trial. Reduction and fixation was
      compared with bipolar hemiarthroplasty with cement and total hip replacement with
      cement. Participating surgeons elected to randomize their patients to be treated
      with either one of the three types of procedures or with either fixation or
      bipolar hemiarthroplasty. Functional outcomes were measured with a hip-rating
      questionnaire and the EuroQol health status measure. Clinical outcomes included
      mortality and complications. The direct health service costs were compared.
      Participants were followed up for two years. RESULTS: Two hundred and seven
      patients were randomized to be treated with one of the three operations, and
      ninety-one were randomized to be treated with either fixation or bipolar
      hemiarthroplasty. There were no differences in the mortality rates among the
      treatment groups. The rate of secondary surgery was highest in the fixation group
      (39% compared with 5% in the group treated with bipolar hemiarthroplasty and 9%
      in the group treated with total hip replacement). The fixation group had the
      worst hip-rating-questionnaire and EuroQol scores at four and twelve months. The
      total hip replacement group had significantly better functional outcome scores at
      twenty-four months than the other two groups. Although fixation was initially the
      least costly procedure, this short-term advantage was eroded by significantly
      higher costs for subsequent hip-related hospital admissions. CONCLUSIONS:
      Arthroplasty is more clinically effective and cost-effective than reduction and
      fixation in healthy older patients with a displaced intracapsular fracture of the
      hip. The long-term results of total hip replacement may be better than those of
      bipolar hemiarthroplasty.

PMID- 16452735
TI  - Prophylaxis against deep-vein thrombosis following trauma: a prospective,
      randomized comparison of mechanical and pharmacologic prophylaxis.
AB  - BACKGROUND: Deep-vein thrombosis following skeletal trauma is an important yet
      poorly studied issue. The purpose of the present study was to evaluate the
      efficacy of two different strategies for prophylaxis against deep-vein thrombosis
      and pulmonary embolus following blunt skeletal trauma. METHODS: Two hundred and
      twenty-four inpatients were enrolled in a prospective, randomized study
      investigating venous thromboembolic disease following trauma. Two hundred
      patients completed the study, which compared two different regimens of
      prophylaxis. The patients in Group A received enoxaparin (30 mg, administered
      subcutaneously twice a day) starting twenty-four to forty-eight hours after blunt
      trauma. The patients in Group B were managed with pulsatile foot pumps at the
      time of admission combined with enoxaparin on a delayed basis. All patients were
      screened with magnetic resonance venography and ultrasonography before discharge.
      RESULTS: There were ninety-seven patients in Group A and 103 patients in Group B.
      Twenty-two patients (including thirteen in Group A and nine in Group B) had
      development of deep-vein thrombosis, with two (both in Group A) also having
      development of pulmonary embolism. The prevalence of deep-vein thrombosis was 11%
      for the whole series, 13.4% for Group A, and 8.7% for Group B; the difference
      between Groups A and B was not significant. There were eleven large or occlusive
      clots (prevalence, 11.3%) in Group A, compared with only three (prevalence, 2.9%)
      in Group B (p = 0.025). The prevalence of pulmonary embolism was 2.1% in Group A
      and 0% in Group B. Wound complications occurred in twenty-one patients in Group
      A, compared with twenty patients in Group B. Patients who had development of deep
      vein thrombosis during the inpatient portion of the study required a mean of 7.4
      units of blood during hospitalization, compared with 3.9 units of blood for those
      who did not (p < 0.05). CONCLUSIONS: Our results indicate that early mechanical
      prophylaxis with foot pumps and the addition of enoxaparin on a delayed basis is
      a very successful strategy for prophylaxis against venous thromboembolic disease
      following serious musculoskeletal injury. The prevalence of large or occlusive
      deep-vein thromboses among patients who had been managed with this protocol was
      significantly less than that among patients who had been managed with enoxaparin
      alone.

PMID- 16452736
TI  - Three-year changes in bone mineral density around the knee after a six-month
      course of oral alendronate following total knee arthroplasty. A prospective,
      randomized study.
AB  - BACKGROUND: Bone mineral density decreases after total knee arthroplasty and is
      believed to affect prosthetic fixation. Treatment with alendronate has been shown
      to improve short-term bone mineral density after total knee arthroplasty;
      however, the long-term effects of this therapy are unknown. The purpose of this
      study was to evaluate the long-term effects of a six-month course of alendronate
      on bone mineral density after total knee arthroplasty. METHODS: Sixty patients
      were randomly assigned to receive either oral alendronate at a dosage of 10
      mg/day for six months or no alendronate. The bone mineral density in the distal
      aspect of the femur and the proximal aspect of the tibia was measured
      preoperatively and at six, twelve, and thirty-six months after total knee
      arthroplasty. RESULTS: Fifty-four patients (twenty-nine in the alendronate group
      and twenty-five in the control group) completed the study. The alendronate group
      showed significant increases in bone mineral density in the distal aspect of the
      femur compared with the controls at six months (+4.8% and -14.2%, respectively; p
      < 0.01) and twelve months (+1.6% and -11.5%, respectively; p < 0.01). No
      significant difference in bone mineral density was detected between the groups at
      thirty-six months (-3.9% and -12.2%, respectively; p = 0.08). Similar trends in
      bone mineral density changes were also observed in the proximal aspect of the
      tibia. CONCLUSIONS: A six-month course of alendronate initially increased bone
      mineral density at six and twelve months after total knee arthroplasty, but no
      difference was noted after thirty-six months. The effect of alendronate on bone
      mineral density after total knee arthroplasty may be limited after
      discontinuation of therapy.

PMID- 16452737
TI  - Evaluation of a single-dose, extended-release epidural morphine formulation for
      pain after knee arthroplasty.
AB  - BACKGROUND: DepoDur is a single-dose, extended-release epidural morphine
      formulation designed to provide forty-eight hours of pain relief. The drug offers
      potential advantages over continuous epidural infusions, particularly in patients
      being treated with anticoagulation therapy. The purpose of this study was to
      evaluate the efficacy and safety of single-dose epidural DepoDur for pain control
      following knee arthroplasty. METHODS: In this multicenter, randomized, double
      blind, parallel-group study, patients were randomized to receive a single-dose of
      DepoDur (20 or 30 mg) or a sham epidural injection thirty minutes before
      administration of general or regional anesthesia for knee arthroplasty. At their
      first request for postoperative analgesia, patients who had received DepoDur were
      given an intravenous bolus of hydromorphone followed by placebo patient
      controlled analgesia. Patients who had received the sham epidural were given an
      intravenous bolus of morphine followed by patient-controlled analgesia with
      morphine. Patient ratings of pain intensity at rest and with activity, their
      rating of overall pain control, and postoperative opioid use were recorded. The
      ability to tolerate physical therapy, the range of motion of the knee, and the
      need for physical support were assessed as well. Adverse events and vital signs
      were recorded. RESULTS: Of 168 patients randomized to receive the 20-mg injection
      of DepoDur, the 30-mg injection of DepoDur, or the sham epidural injection, fifty
      one, fifty-eight, and fifty-five patients, respectively, were included in the
      efficacy analysis. Compared with the patients treated with intravenous patient
      controlled analgesia with morphine, the patients treated with DepoDur had
      significantly reduced mean pain-intensity-recall scores during the four to eight,
      four to twelve, four to twenty-four, and four to thirty-hour postdose intervals
      (p < 0.05 for all comparisons). The patients treated with DepoDur used
      approximately a threefold lower amount of postoperative opioids in total, with a
      significant percentage requiring no supplemental opioids. Adverse events common
      to all groups were nausea (78%), pyrexia (46%), vomiting (43%), pruritus (43%),
      and hypotension (36%). Respiratory depression was the most common serious adverse
      event, with serious respiratory depression observed in four DepoDur-treated
      patients, who were more than sixty-five years of age. CONCLUSIONS: With
      appropriate patient selection and monitoring, perioperative single-dose epidural
      DepoDur was a safe and effective analgesic alternative to postoperative
      intravenous patient-controlled analgesia following knee arthroplasty, with
      younger patients benefiting from the 20-mg dose. Additional studies of 10 to 15
      mg doses for older patients are warranted.

PMID- 16452738
TI  - A multimodal analgesia protocol for total knee arthroplasty. A randomized,
      controlled study.
AB  - BACKGROUND: Although numerous methods of postoperative analgesia have been
      investigated in an attempt to improve pain control after total knee arthroplasty,
      parenteral narcotics still play a major role in postoperative pain management.
      Local anesthetics have the advantage of blocking pain conduction at its origin
      and minimizing the systemic side effects associated with postoperative narcotic
      use. This study was performed to evaluate the benefits and safety of a multimodal
      analgesia protocol that included periarticular injection of large doses of local
      anesthetics in patients undergoing total knee arthroplasty. METHODS: We compared
      morphine consumption during the first twenty-four hours after unilateral total
      knee arthroplasty in forty-two patients who had been randomized to receive either
      (1) a perioperative infiltration mixture, consisting principally of local
      anesthetic, and self-administered morphine or (2) self-administered morphine
      only. Narcotics consumption, pain control, medication-related side effects,
      plasma levels of the local anesthetic (ropivacaine), and postoperative
      rehabilitation were monitored. RESULTS: Although there was high satisfaction and
      good pain control in both groups, morphine consumption was significantly lower in
      the local analgesia group than it was in the control group (28.8 +/- 17.4 mg
      compared with 50.3 +/- 25.4 mg twenty-four hours after surgery, and 46.7 +/- 19.4
      mg compared with 68.6 +/- 38.6 mg forty hours after surgery). Both groups
      achieved a similar amount of knee flexion on the fifth postoperative day. Over
      the five-day period after the procedure, the patients in the local analgesia
      group reported a total of 2.6 +/- 3.9 hours of nausea compared with 7.1 +/- 12.2
      hours in the control group. No complications related to the infiltration of the
      local anesthetic were observed, and all plasma concentrations of the local
      anesthetic were below the toxic range. CONCLUSIONS: This multimodal perioperative
      analgesia protocol that included infiltration of a local anesthetic offered
      improved pain control and minimal side effects to patients undergoing total knee
      arthroplasty. Our study also confirmed the safety of the protocol.

PMID- 16452739
TI  - Hospital cost of dislocation after primary total hip arthroplasty.
AB  - BACKGROUND: The treatment of dislocation following primary total hip arthroplasty
      usually requires the use of expensive hospital resources and sometimes requires
      revision surgery. The hospital costs associated with treating this complication
      have not been previously analyzed, to our knowledge. The purpose of this study
      was to assess the financial impact of treating dislocations at our institution.
      METHODS: Between 1997 and 2001, 3671 patients underwent a total of 4054
      consecutive primary total hip arthroplasties at our institution. The patients
      were prospectively followed at regular intervals, and their follow-up data were
      recorded in an institutional total joint registry. Ninety-nine hips (2.4%) in
      ninety-nine patients dislocated. The costs to our institution to treat these
      dislocations were evaluated by determining the cost of each treatment episode
      required to reestablish hip stability and were expressed as the percent increase
      in cost compared with that of an uncomplicated primary total hip replacement.
      RESULTS: Of the ninety-nine hips that dislocated, sixty-two (63%) remained stable
      after one or more closed reductions and thirty-seven (37%) ultimately required
      revision surgery. The hospital cost of each closed reduction episode represented
      19% of the hospital cost of an uncomplicated total hip replacement. When revision
      surgery was eventually needed, the average hospital costs of one or more closed
      reductions and the subsequent revisions represented 148% of the hospital cost of
      an uncomplicated primary total hip replacement. CONCLUSIONS: Dislocation after
      primary hip replacement continues to be a prevalent and costly complication that
      diminishes the cost-effectiveness of an otherwise very successful surgical
      procedure.

PMID- 16452740
TI  - Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled,
      randomized, double-blind pilot study.
AB  - BACKGROUND: Intra-articular injections of hyaluronans have been shown to be safe
      and effective for the treatment of pain associated with osteoarthritis of the
      knee. This pilot study was undertaken to gather preliminary data on the efficacy
      and safety of five weekly intra-articular injections of Hyalgan (sodium
      hyaluronate; molecular weight, 500 to 730 kDa) as compared with saline solution
      for the treatment of pain associated with osteoarthritis of the ankle. METHODS:
      Twenty patients at two test sites were randomized with use of a double-blind
      (blinded observer), saline solution-controlled, parallel experimental design.
      Patients were randomized to receive five weekly intra-articular injections of
      either 1 mL of sodium hyaluronate (10 mg/mL) or 1 mL of phosphate-buffered saline
      solution into the ankle joint. The primary outcome measurement was the ankle
      osteoarthritis score. Several secondary outcome measures also were assessed.
      RESULTS: Significant improvement in the mean ankle osteoarthritis score from
      baseline was seen at all follow-up visits from one to six months in both the
      sodium hyaluronate group and the saline solution group (p < 0.0001). In addition,
      five of nine patients in the sodium hyaluronate group had >30 mm of improvement
      in this score, compared with one of eight patients in the control group. No
      withdrawals were directly attributable to the injections of sodium hyaluronate or
      saline solution, and no severe medication-related adverse events were observed.
      CONCLUSIONS: The present study suggests that five weekly intra-articular
      injections of sodium hyaluronate (molecular weight, 500 to 730 kDa) are well
      tolerated, can provide sustained relief of pain, and can improve function in
      patients with osteoarthritis of the ankle. These findings are consistent with
      those of previously published studies involving intra-articular injections of
      sodium hyaluronate in other joints, but they require confirmation in a large,
      randomized, saline solution-controlled study.

PMID- 16452741
TI  - Autologous chondrocyte transplantation for treating cartilage defects of the
      talus.
AB  - BACKGROUND: Despite its highly specialized nature, articular cartilage has a poor
      reparative capability. Treatment of symptomatic osteochondral defects of the
      talus has been especially difficult until now. METHODS: We performed autologous
      chondrocyte transplantation in twelve patients with a focal deep cartilage lesion
      of the talus. There were seven female and five male patients with a mean age of
      29.7 years. The mean size of the lesion was 2.3 cm(2). All patients were studied
      prospectively. Evaluation was performed with use of the Hannover ankle rating
      score, the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot
      score, a visual analogue scale for pain, and magnetic resonance imaging. RESULTS:
      All patients were available for follow-up at a mean of sixty-three months. There
      was a significant improvement in the Hannover score, from 40.4 points
      preoperatively to 85.5 points at the follow-up examination, with seven excellent
      results, four good results, and one satisfactory result. The AOFAS mean score was
      88.4 points compared with 43.5 points preoperatively. Magnetic resonance imaging
      showed a nearly congruent joint surface in seven patients, discrete
      irregularities in four, and an incongruent surface in one. The patients who had
      been involved in competitive sports were able to return to their full activity
      level. CONCLUSIONS: The promising clinical results of this study suggest that
      autologous chondrocyte transplantation is an effective and safe way to treat
      symptomatic osteochondral defects of the talus in appropriately selected
      patients.

PMID- 16452742
TI  - Clinical and structural results of open repair of an isolated one-tendon tear of
      the rotator cuff.
AB  - BACKGROUND: The clinical outcomes of open rotator cuff repair are well
      established, but the structural results and their effect on clinical outcome are
      poorly known. We assessed the structural changes in the musculotendinous units
      after open rotator cuff repair and correlated these findings with the clinical
      outcome to establish a benchmark for future series. METHODS: Thirty-two
      consecutive standardized open repairs of a single tendon tear of the rotator cuff
      were analyzed in twenty-one men and eleven women with an average age of 59.0
      years. The supraspinatus tendon was involved in twenty-two patients and the
      subscapularis tendon, in ten. The clinical outcome, including the Constant score,
      was assessed prospectively for all patients at an average of thirty-eight months
      postoperatively. The structural outcome was assessed on standardized magnetic
      resonance imaging scans. RESULTS: The mean overall subjective shoulder value was
      82.8% of the value for a normal shoulder. On the average, the age and gender
      adjusted Constant score increased from 63.9% preoperatively to 94.5%
      postoperatively (p < 0.0001); the score for pain, from 6.8 points to 13.2 points
      (p < 0.0001); and the score for activities of daily living, from 11.2 points to
      17.9 points (p < 0.0001). The overall rerupture rate was 13% (four of the thirty
      two shoulders). All reruptures were distinctly smaller than the original tear.
      Muscular atrophy or fatty infiltration did not significantly decrease after the
      tendon repair. In fact, fatty infiltration in the supraspinatus (p < 0.0053) and
      infraspinatus (p < 0.003) muscles increased significantly. CONCLUSIONS: Direct
      open repair of a complete, isolated tear of one tendon of the rotator cuff
      resulted in significant subjective and objective improvement and very high
      patient satisfaction. Successful direct repair was not associated with a decrease
      in preoperative muscular atrophy and was associated with increased fatty
      infiltration of the muscle.

PMID- 16452743
TI  - High pain ratings predict treatment failure in chronic occupational
      musculoskeletal disorders.
AB  - BACKGROUND: Pain intensity is one of the most widely used measures in the
      treatment of patients with chronic disabling occupational musculoskeletal
      disorders. Few studies have comprehensively investigated the relationship of pain
      intensity at the time of rehabilitation to objective socioeconomic outcomes at
      one year after treatment. This study evaluated the ability of pain intensity
      ratings, measured with a visual analog scale, to predict rehabilitation outcomes
      and to identify patients who are "at risk" for a poor outcome. METHODS: A cohort
      of 3106 patients with chronic disabling occupational musculoskeletal disorders in
      a multidisciplinary occupational tertiary rehabilitation program was divided into
      four groups on the basis of the pain intensity ratings (0 to 3, 4 to 5, 6 to 7,
      and 8 to 10) before and after rehabilitation. A structured interview to assess
      the socioeconomic outcomes, including work status, health-care utilization,
      recurrent injury, and whether there had been resolution of Workers' Compensation
      or third-party financial disputes, was conducted one year after rehabilitation.
      RESULTS: High pain intensity before rehabilitation was linearly associated with
      declining rates of program completion and higher rates of self-reported
      depression and disability after rehabilitation. Although higher pain ratings both
      before and after rehabilitation were associated linearly with a declining quality
      of socioeconomic outcomes, extremely high pain ratings (8 to 10) after
      rehabilitation were most predictive of poor outcomes. At the post-rehabilitation
      evaluation, patients with extreme pain were far more likely than those with mild
      pain to seek surgical treatment (risk ratio = 11.2 [95% confidence interval, 4.3,
      29.5]) or to persist in seeking health care from new providers (risk ratio = 3.3
      [95% confidence interval, 2.4, 4.5]). They were less likely to either return to
      work (risk ratio = 3.9 [95% confidence interval, 2.6, 6.0]) or to retain work
      (risk ratio = 4.2 [95% confidence interval, 2.9, 6.0]). They were also twice as
      likely to claim a new injury to the same musculoskeletal site after returning to
      work and to fail to settle Workers' Compensation or third-party financial
      disputes. CONCLUSIONS: High pain ratings before rehabilitation are associated
      with higher rehabilitation dropout rates. The patients with chronic disabling
      occupational musculoskeletal disorders who reported extreme pain after completing
      a full course of extended treatment (13% of 2573) were at risk for poor outcomes
      in terms of lost productivity, high utilization of health care, and cost-shifting
      of state Workers' Compensation payments to federal resources.

PMID- 16452744
TI  - Validation of the Shriners Hospital for Children Upper Extremity Evaluation
      (SHUEE) for children with hemiplegic cerebral palsy.
AB  - BACKGROUND: The Shriners Hospital for Children Upper Extremity Evaluation (SHUEE)
      is a video-based tool for the assessment of upper extremity function in children
      with hemiplegic cerebral palsy. This tool includes spontaneous functional
      analysis and dynamic positional analysis and assesses the ability to perform
      grasp and release. The purpose of the present study was to assess the
      reliability, concurrent validity, and construct validity of this instrument.
      METHODS: The Shriners Hospital for Children Upper Extremity Evaluation studies
      for eleven subjects with hemiplegic cerebral palsy were selected for the
      evaluation of intraobserver and interobserver reliability. Concurrent validity
      was determined through analysis of the Shriners Hospital for Children Upper
      Extremity Evaluation, Pediatric Evaluation of Disability Inventory, and Jebson
      Taylor Test of Hand Function scores for twenty children. Construct validity was
      determined through analysis of Shriners Hospital for Children Upper Extremity
      Evaluation scores for eighteen children before and after flexor carpi ulnaris to
      extensor carpi radialis brevis tendon transfer. RESULTS: The absolute mean
      differences between the two scoring sessions for three raters were 1.2 and 1.0
      for the spontaneous functional analysis and the dynamic positional analysis,
      respectively. Although the mean differences were significantly different from 0
      (p < 0.001 and p = 0.003), the differences were small and not clinically
      important with regard to the total possible score. There was excellent
      intraobserver reliability between the two sessions with regard to both
      spontaneous functional analysis (r = 0.99) and dynamic positional analysis (r =
      0.98). Assessment of interobserver reliability revealed absolute mean differences
      between four raters of 3.8 and 3.7 for the spontaneous functional analysis and
      the dynamic positional analysis, respectively. These differences were
      significantly different from 0 (p < 0.001); however, the magnitudes of these
      differences were not important with regard to total score or clinical
      interpretation. There was excellent interobserver reliability for both the
      spontaneous functional analysis (r = 0.90) and the dynamic positional analysis (r
      = 0.89). There was 100% agreement within and between examiners for the grasp-and
      release section. The Shriners Hospital for Children Upper Extremity Evaluation
      showed fair correlation with the self-care scaled score from the Pediatric
      Evaluation of Disability Inventory (r = 0.47) and good inverse correlation with
      the non-dominant total time section of the Jebson-Taylor test (r = -0.76). The
      Shriners Hospital for Children Upper Extremity Evaluation wrist score improved
      for all eighteen subjects after the flexor tendon transfer, and the mean
      improvement was significant (p < 0.001). CONCLUSIONS: The present study
      establishes the clinical reliability, concurrent validity, and construct validity
      of the Shriners Hospital for Children Upper Extremity Evaluation for the
      assessment of upper extremity function in children with hemiplegic cerebral
      palsy.

PMID- 16452745
TI  - Prospective measurement of function and pain in patients with non-neoplastic
      compression fractures treated with vertebroplasty.
AB  - BACKGROUND: There has been an increasing number of reports regarding the benefits
      of vertebroplasty for the treatment of vertebral compression fractures. In this
      investigation, validated outcome tools were utilized to document the impact of
      vertebroplasty on pain and function. METHODS: Fifty patients were recruited at a
      tertiary university hospital. Patients had been treated for intractable pain due
      to osteoporotic compression fracture(s) for at least four weeks. The
      vertebroplasty procedures were performed by a radiologist. The subjects were
      followed prospectively for one year and received conservative treatment in
      conjunction with the vertebroplasty. Validated outcome tools, including a visual
      analog scale, the Oswestry scale, and the Roland-Morris functional activity
      questionnaire, were used to evaluate changes in pain and functional capabilities.
      RESULTS: Fifty patients, thirty-one women and nineteen men (mean age, 68.6
      years), were followed prospectively for one year. One hundred and three fractures
      (fifty-nine thoracic and forty-four lumbar) were treated. The visual analog scale
      showed the greatest improvement between the baseline score (mean, 7.76) and the
      score at one month (mean, 2.9), and the score remained improved at one year
      (mean, 2.9). The Oswestry and Roland-Morris questionnaires demonstrated
      significant (p < 0.0001) functional improvement between the baseline and one
      month scores. With the numbers available, there were no significant changes in
      any variable from one month to one year (p > 0.05). CONCLUSIONS: Vertebroplasty
      is an effective treatment for patients with intractable pain due to osteoporotic
      vertebral compression fractures. Improvement in pain scores and functional
      capabilities that were found at one month were maintained at one year.

PMID- 16452746
TI  - Latissimus dorsi tendon transfer for irreparable posterosuperior rotator cuff
      tears. Factors affecting outcome.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical results of
      latissimus dorsi tendon transfer in patients with an irreparable posterosuperior
      rotator cuff tear to help determine which patient and anatomic factors affect
      clinical outcome. METHODS: Fourteen patients with a latissimus dorsi tendon
      transfer were clinically evaluated with use of the PENN (University of
      Pennsylvania) shoulder score as well as with quantitative measurement of
      isometric muscle strength and the range of motion of both shoulders at a minimum
      of twenty-four months postoperatively. The anatomic results were evaluated with
      postoperative magnetic resonance imaging and electromyography. RESULTS: Nine
      patients were satisfied with the outcome, had significant clinical improvement,
      and reported that they would have the operation again under similar
      circumstances. The other five patients were dissatisfied with the result and had
      significantly worse PENN scores, active elevation, and objective measures of
      strength. Eight of the nine patients with a good clinical result were male, and
      four of the five with a poor result were female. Patients with a good clinical
      result had had significantly better preoperative function in active forward
      flexion and active external rotation compared with the patients with a poor
      result. The magnetic resonance imaging demonstrated healing of the tendon to the
      greater tuberosity in twelve patients and equivocal healing in two. There was no
      significant atrophy of any of the transferred muscles. Electromyography
      demonstrated clear activity in the transferred latissimus muscle during humeral
      adduction in all fourteen patients, some electrical activity with active forward
      elevation in only one patient, and some electrical activity with active external
      rotation in six of the nine patients with a good clinical result. None of the
      patients with a poor clinical result demonstrated electrical activity of the
      transferred muscle with active forward flexion or external rotation. CONCLUSIONS:
      Synchronous in-phase contraction of the transferred latissimus dorsi is a
      variable finding following the surgical treatment of irreparable posterosuperior
      rotator cuff tears, but when it is present it is associated with a better
      clinical result. Preoperative shoulder function and general strength influence
      the clinical result. Female patients with poor shoulder function and generalized
      muscle weakness prior to surgery have a greater likelihood of having a poor
      clinical result.

PMID- 16452747
TI  - Treatment of external fixation pins about the wrist: a prospective, randomized
      trial.
AB  - BACKGROUND: Pin-track infection remains one of the most troublesome complications
      of external fixation, in some cases compromising otherwise successful fracture
      treatment. METHODS: One hundred and eighteen patients (120 wrists) who had been
      managed with the placement of an external fixation device for the treatment of a
      displaced, unstable, distal radial fracture were randomized into one of three
      treatment groups: (1) weekly dry dressing changes without pin-site care; (2)
      daily pin-site care with a solution of one-half normal saline solution and one
      half hydrogen peroxide; and (3) treatment with the placement of chlorhexidine
      impregnated discs (Biopatch) around the pins, with weekly changes of the discs by
      the treating surgeon. The patients were followed at weekly intervals until the
      external fixator was removed. Radiographs were made biweekly. The patients were
      evaluated with regard to (1) erythema, (2) cellulitis, (3) drainage, (4) clinical
      or radiographic evidence of pin-loosening, (5) the need for antibiotics, and (6)
      the need for pin removal before fracture-healing due to infection. Differences in
      complication rates among the three groups, with adjustment for patient age,
      gender, and the performance of an associated open procedure, were evaluated.
      RESULTS: The average age of the patients was fifty-four years. Forty-seven wrists
      had an open procedure (either bone-grafting or open reduction and internal
      fixation) in addition to treatment with the external fixator. The fixators
      remained in place for an average of 5.9 weeks. Twenty-three patients (19%) had a
      complication related to the pin track, with twelve of these patients requiring
      oral antibiotics for the treatment of a pin-track infection. There were no
      significant differences among the three groups with regard to the prevalence of
      pin-site complications. The age of the patient was found to be significantly
      associated with an increased risk of postoperative pin-track complications (p =
      0.04). CONCLUSIONS: We found a high rate of local wound complications around
      external fixation pin sites; however, most complications were minor and could be
      observed or treated with oral antibiotics. The prevalence of these complications
      was not decreased in association with the use of hydrogen peroxide wound care or
      chlorhexidine-impregnated dressings. On the basis of these results, we do not
      recommend additional wound care beyond the use of dry, sterile dressings for pin
      track care after external fixation for the treatment of distal radial fractures.

PMID- 16452748
TI  - Direct percutaneous gene delivery to enhance healing of segmental bone defects.
AB  - BACKGROUND: Healing of segmental bone defects can be induced experimentally with
      genetically modified osteoprogenitor cells, an ex vivo strategy that requires two
      operative interventions and substantial cost. Direct transfer of osteogenic genes
      offers an alternative, clinically expeditious, cost-effective approach. We
      evaluated its potential in a well-established, critical-size, rat femoral defect
      model. METHODS: A critical-size defect was created in the right femur of forty
      eight skeletally mature Sprague-Dawley rats. After twenty-four hours, each defect
      received a single, intralesional, percutaneous injection of adenovirus carrying
      bone morphogenetic protein-2 (Ad.BMP-2) or luciferase cDNA (Ad.luc) or it
      remained untreated. Healing was monitored with weekly radiographs. At eight
      weeks, the rats were killed and the femora were evaluated with dual-energy x-ray
      absorptiometry, micro-computed tomography, histological analysis,
      histomorphometry, and torsional mechanical testing. RESULTS: Radiographically,
      75% of the Ad.BMP-2-treated femora showed osseous union. Bone mineral content was
      similar between the Ad.BMP-2-treated femora (0.045 +/- 0.020 g) and the
      contralateral, intact femora (0.047 +/- 0.003 g). Histologically, 50% of the
      Ad.BMP-2-treated defects were bridged by lamellar, trabecular bone; the other 50%
      contained islands of cartilage. The control (Ad.luc-treated) defects were filled
      with fibrous tissue. Histomorphometry demonstrated a large difference in
      osteogenesis between the Ad.BMP-2 group (mean bone area, 3.25 +/- 0.67 mm(2)) and
      the controls (mean bone area, 0.65 +/- 0.67 mm(2)). By eight weeks, the Ad.BMP-2
      treated femora had approximately one-fourth of the strength (mean, 0.07 +/- 0.04
      Nm) and stiffness (mean, 0.5 +/- 0.4 Nm/rad) of the contralateral femora (0.3 +/-
      0.08 Nm and 2.0 +/- 0.5 Nm/rad, respectively). CONCLUSIONS: A single,
      percutaneous, intralesional injection of Ad.BMP-2 induces healing of critical
      size femoral bone defects in rats within eight weeks. At this time, the repair
      tissue is predominantly trabecular bone, has normal bone mineral content, and has
      gained mechanical strength.

PMID- 16452749
TI  - McKeever hemiarthroplasty of the knee in patients less than sixty years old.
AB  - BACKGROUND: Knee arthritis in the young patient is a challenging problem that may
      necessitate surgical treatment. We continue to perform hemiarthroplasty with a
      metallic tibial implant in selected young patients who, for various reasons, are
      not candidates for osteotomy, unicompartmental arthroplasty, or total knee
      arthroplasty. The purpose of the present study was to determine the minimum
      twelve-year results of this procedure in young patients. METHODS: The original
      study group consisted of a consecutive series of twenty-four patients (twenty-six
      knees) who were managed with McKeever tibial hemiarthroplasty for the treatment
      of unicompartmental osteoarthritis of the knee. All patients were younger than
      sixty years of age at the time of the index procedure (average age, 44.6 years).
      During the study period, two patients died and one was lost to follow-up, leaving
      twenty-one patients (twenty-three knees) available for review. All patients were
      followed clinically for a minimum of twelve years or until revision. Knee Society
      knee and functional scores and Tegner scores were determined, and seven of the
      ten implants were evaluated radiographically. RESULTS: Thirteen knees were
      revised at an average of eight years after the index procedures. All thirteen
      knees had an uncomplicated revision to either a unicompartmental arthroplasty or
      total knee arthroplasty. Ten retained implants were available for clinical review
      after an average duration of follow-up of 16.8 years. The mean Knee Society knee
      scores, functional scores, and Tegner scores, available for nine of these ten
      knees, were 80, 97, and 4.2, respectively. CONCLUSIONS: We believe that the
      McKeever tibial hemiarthroplasty continues to be a reasonable surgical option for
      patients who are not candidates for osteotomy and are too young or too active for
      a unicompartmental or total knee arthroplasty.

PMID- 16452750
TI  - The prevalence of acetabular retroversion among various disorders of the hip.
AB  - BACKGROUND: Acetabular retroversion can result from posterior wall deficiency in
      an otherwise normally oriented acetabulum or from excessive anterior coverage
      secondary to a malpositioned acetabulum, or both. Theoretically, a retroverted
      acetabulum, which adversely affects load transmission across the hip, may occur
      more frequently in hips with degenerative arthritis. The aim of this study was to
      assess the prevalence of acetabular retroversion in normal hips and in hips with
      osteoarthritis, developmental dysplasia, osteonecrosis, and Legg-Calve-Perthes
      disease. METHODS: We retrospectively examined anteroposterior radiographs of the
      pelvis of 250 patients (342 hips). Fifty-six patients (112 hips) had normal
      findings; sixty-six patients (seventy hips) had osteoarthritis; sixty-four
      (seventy-four hips), developmental dysplasia; thirty (thirty-six hips),
      osteonecrosis of the femoral head; and thirty-four (fifty hips), Legg-Calve
      Perthes disease. The sole criterion for a diagnosis of acetabular retroversion
      was the presence of a so-called cross-over sign on the anteroposterior radiograph
      of the pelvis. RESULTS: The prevalence of acetabular retroversion was 6% (seven
      of 112 hips) in the normal group, 20% (fourteen of seventy hips) in the
      osteoarthritis group, 18% (thirteen of seventy-four hips) in the developmental
      dysplasia group, 6% (two of thirty-six hips) in the group with osteonecrosis of
      the femoral head, and 42% (twenty-one of fifty hips) in the group with Legg-Calve
      Perthes disease. In patients with Legg-Calve-Perthes disease, the prevalence of
      acetabular retroversion was 68% in twenty-five hips with Stulberg class-III, IV,
      or V involvement. In contrast, only four (16%) of twenty-five hips with Stulberg
      class-I or II involvement had acetabular retroversion. The difference was
      significant (p = 0.0002). Patients with osteoarthritis, developmental dysplasia,
      or Legg-Calve-Perthes disease are significantly more likely to have acetabular
      retroversion than are normal subjects (p < 0.05). CONCLUSIONS: Acetabular
      retroversion occurs more commonly in association with a variety of hip diseases,
      in which the prevalence of subsequent degenerative arthritis is increased, than
      has been previously noted.

PMID- 16452751
TI  - Femoral deformity in tibia vara.
AB  - BACKGROUND: Previous studies have suggested that compensatory valgus deformity of
      the femur is common in patients with tibia vara, or Blount disease. The
      availability and routine use of standing long-cassette radiographs of the lower
      extremities to assess angular deformities has allowed quantitative evaluation of
      this hypothesis. METHODS: The cases of all patients with tibia vara, two years of
      age or older, seen at our institution prior to treatment, over a thirteen-year
      period, were reviewed. Seventy-three patients with a total of 109 involved lower
      limbs were identified and were classified as having either infantile tibia vara
      (thirty-seven patients with fifty-six involved limbs) or late-onset tibia vara
      (thirty-six patients with fifty-three involved limbs). Standardized standing
      radiographs of the lower extremity were examined to assess the deformity at the
      distal part of the femur and the proximal part of the tibia by measuring the
      lateral distal femoral angle and the medial proximal tibial angle. RESULTS: The
      distal part of the femur in the children with infantile tibia vara either was
      normal or had mild varus deformity, with a mean lateral distal femoral angle of
      97 degrees (range, 82 degrees to 129 degrees). The mean medial proximal tibial
      angle in these children was 72 degrees (range, 32 degrees to 84 degrees). Older
      children with infantile tibia vara were noted to have little distal femoral
      deformity, with no more than 4 degrees of valgus compared with either normal
      values or the contralateral, normal limb. Children with late-onset tibia vara had
      a mean lateral distal femoral angle of 93 degrees (range, 82 degrees to 110
      degrees) and a mean medial proximal tibial angle of 73 degrees (range, 52 degrees
      to 84 degrees). On the average, the varus deformity of the distal part of the
      femur constituted 30% (6 degrees of 20 degrees) of the genu varum deformity in
      these patients. CONCLUSIONS: Patients with infantile tibia vara most commonly had
      normal alignment of the distal parts of the femora; substantial valgus deformity
      was not observed. Distal femoral varus constituted a substantial portion of the
      genu varum in children with late-onset disease. When correction of late-onset
      tibia vara is planned, the surgeon should be aware of the possibility that distal
      femoral varus is a substantial component of the deformity.

PMID- 16452752
TI  - Cementless acetabular reconstruction and structural bone-grafting in dysplastic
      hips.
AB  - BACKGROUND: Studies of acetabular reconstruction with use of cement and bulk bone
      graft have demonstrated increasing rates of cup failure in patients with
      dysplastic hips seven years after total hip arthroplasty. Comparable data on the
      long-term results of bulk bone-grafting done in conjunction with cementless
      implants are limited. The aim of this study was to review the clinical and
      radiographic results of autologous bulk bone-grafting in conjunction with a
      cementless cup. METHODS: From 1987 to 1992, forty-seven patients (forty women and
      seven men, with an average age of 50.4 years) who had developmental dysplasia of
      the hip underwent fifty-six total hip arthroplasties and received a structural
      graft in combination with a cementless Harris-Galante type-I cup. All patients
      were followed prospectively. In fifty-five hips, implant migration was measured
      with single-image radiographic analysis. RESULTS: After an average duration (and
      standard deviation) of 10.2 +/- 2.9 years, three patients (four hips) had died.
      In the surviving patients, four implants had been revised and two had
      radiographic evidence of loosening. With use of revision and loosening as end
      points, the eleven-year survival rates were 91.6% and 88.9%, respectively. Of the
      fifty implants that had no loosening, fourteen had measurable cup migration,
      thirty-five had no migration, and one implant could not be measured. All
      migrations but one were progressive. With loosening used as the end point, the
      survival rate at eleven years was 100% for the implants with no migration;
      however, the survival rate for the cups that had migrated was 69.3% (p = 0.0012).
      CONCLUSIONS: The eleven-year survival rate for the spherical press-fit cups in
      combination with bulk bone-grafting is satisfactory, given the complexity of
      these reconstructions. However, the difference between the survival of the
      implants that had migrated and those that had not was significant. We expect that
      the thirteen implants with progressive acetabular migration at the time of the
      latest follow-up are at risk for loosening, which will increase the revision rate
      for this series in the coming years.

PMID- 16452753
TI  - Three-dimensional tibiofemoral articular contact kinematics of a cruciate
      retaining total knee arthroplasty.
AB  - BACKGROUND: Accurate knowledge of the location of tibiofemoral articular contact
      following total knee arthroplasty is important in order to understand
      polyethylene wear and the mechanisms of component failure. The present study was
      performed to determine the three-dimensional tibiofemoral articular contact
      patterns of a posterior cruciate ligament-retaining total knee replacement during
      in vivo weight-bearing flexion. METHODS: Nine osteoarthritic patients who were
      managed with a single design of a posterior cruciate ligament-retaining total
      knee implant were investigated with the use of an innovative dual orthogonal
      fluoroscopic imaging system. The position of the components during in vivo weight
      bearing flexion was measured from full extension to maximum flexion in 15 degrees
      intervals. Tibiofemoral articular contact was determined by the overlap of the
      tibiofemoral articular surfaces. The centroid of the surface intersection was
      used to report the point of contact location. The average tibiofemoral contact
      points on both the medial and lateral tibial component surfaces were reported as
      a function of flexion. RESULTS: The average maximum weight-bearing flexion angle
      was 113.3 degrees +/- 13.1 degrees (range, 96 degrees to 138 degrees ). In the
      anteroposterior direction, the contact location was relatively constant in the
      medial compartment and moved posteriorly by 5.6 mm in the lateral compartment as
      the knee flexed from full extension to 90 degrees of flexion. The range of the
      contact location in the mediolateral direction was 3.7 mm in the medial
      compartment and 4.8 mm in the lateral compartment. For both compartments,
      posterior translation of the contact point was significant from 90 degrees to
      maximum flexion, but the contact point at maximum flexion was not observed to
      reach the posterior edge of the polyethylene tibial insert articular surface.
      CONCLUSIONS: While the minimum anteroposterior translation of the contact point
      on the medial side might be interpreted as a medial pivot rotation during knee
      flexion, the contact point did move in the mediolateral direction with flexion.
      Beyond 90 degrees , both medial and lateral contact points were shown to move
      posteriorly but stopped before reaching the posterior edge of the polyethylene
      tibial insert articular surface. It seemed that the current component design did
      not allow the femoral condyle to roll off the polyethylene edge at high degrees
      of flexion because of the geometry at the posterior lip.

PMID- 16452754
TI  - Biomechanical evaluation of arthroscopic rotator cuff repairs: double-row
      compared with single-row fixation.
AB  - BACKGROUND: Recent studies have shown that arthroscopic rotator cuff repairs can
      have higher rates of failure than do open repairs. Current methods of rotator
      cuff repair have been limited to single-row fixation of simple and horizontal
      stitches, which is very different from open repairs. The objective of this study
      was to compare the initial cyclic loading and load-to-failure properties of
      double-row fixation with those of three commonly used single-row techniques.
      METHODS: Ten paired human supraspinatus tendons were split in half, yielding four
      tendons per cadaver. The bone mineral content at the greater tuberosity was
      assessed. Four stitch configurations (two-simple, massive cuff, arthroscopic
      Mason-Allen, and double-row fixation) were randomized and tested on each set of
      tendons. Specimens were cyclically loaded between 5 and 100 N at 0.25 Hz for
      fifty cycles and then loaded to failure under displacement control at 1 mm/sec.
      Conditioning elongation, peak-to-peak elongation, ultimate tensile load, and
      stiffness were measured with use of a three-dimensional tracking system and
      compared, and the failure type (suture or anchor pull-out) was recorded. RESULTS:
      No significant differences were found among the stitches with respect to
      conditioning elongation. The mean peak-to-peak elongation (and standard error of
      the mean) was significantly lower for the massive cuff (1.1 +/- 0.1 mm) and
      double-row stitches (1.1 +/- 0.1 mm) than for the arthroscopic Mason-Allen stitch
      (1.5 +/- 0.2 mm) (p < 0.05). The ultimate tensile load was significantly higher
      for double-row fixation (287 +/- 24 N) than for all of the single-row fixations
      (p < 0.05). Additionally, the massive cuff stitch (250 +/- 21 N) was found to
      have a significantly higher ultimate tensile load than the two-simple (191 +/- 18
      N) and arthroscopic Mason-Allen (212 +/- 21 N) stitches (p < 0.05). No
      significant differences in stiffness were found among the stitches. Failure
      mechanisms were similar for all stitches. Rotator cuff repairs in the anterior
      half of the greater tuberosity had a significantly lower peak-to-peak elongation
      and higher ultimate tensile strength than did repairs on the posterior half.
      CONCLUSIONS: In this in vitro cadaver study, double-row fixation had a
      significantly higher ultimate tensile load than the three types of single-row
      fixation stitches. Of the single-row fixations, the massive cuff stitch had
      cyclic and load-to-failure characteristics similar to the double-row fixation.
      Anterior repairs of the supraspinatus tendon had significantly stronger
      biomechanical behavior than posterior repairs.

PMID- 16452755
TI  - Use of an Ilizarov apparatus to perform closed reduction of a chronic proximal
      dislocation following total hip arthroplasty. A case report.

PMID- 16452756
TI  - Bilateral patella cubiti. A case report.

PMID- 16452757
TI  - Acute compartment syndrome of the thigh following rupture of the quadriceps
      tendon. A case report.

PMID- 16452758
TI  - Management of elbow osteoarthritis.
AB  - Primary osteoarthritis of the elbow is characterized by painful stiffness,
      mechanical symptoms, and the presence of hypertrophic osteophytes. Preservation
      of the joint space is common and may account for the good results that are
      usually achieved with nonoperative treatment and nonprosthetic arthroplasty.
      Elbow osteoarthritis typically affects middle-aged men who engage in strenuous
      manual activity. Open or arthroscopic capsular release and removal of impinging
      osteophytes are the primary surgical treatment options. The relative sparing of
      joint cartilage makes elbow osteoarthritis unique in this regard and amenable to
      this treatment. Arthroplasty is rarely indicated for primary osteoarthritis of
      the elbow and should be reserved for elderly individuals with low demands for
      whom other treatment options have failed.

PMID- 16452759
TI  - In the beginning was the word.

PMID- 16452760
TI  - Are validated questionnaires valid?

PMID- 16452761
TI  - Are validated questionnaires valid?

PMID- 16452762
TI  - Editor's note.

PMID- 16452764
TI  - Are validated questionnaires valid?

PMID- 16452765
TI  - Are validated questionnaires valid?

PMID- 16452766
TI  - Are validated questionnaires valid?

PMID- 16452768
TI  - Leadership in orthopaedics: taking a stand to own the bone.

PMID- 16452770
TI  - Grades of recommendation.

PMID- 16452772
TI  - Comparison of soap and antibiotic solutions for irrigation of lower-limb open
      fracture wounds.

PMID- 16452776
TI  - What's new in sports medicine.

PMID- 16452777
TI  - Clustering binary fingerprint vectors with missing values for DNA array data
      analysis.
AB  - Oligonucleotide fingerprinting is a powerful DNA array based method to
      characterize cDNA and ribosomal RNA gene (rDNA) libraries and has many
      applications including gene expression profiling and DNA clone classification. We
      are especially interested in the latter application. A key step in the method is
      the cluster analysis of fingerprint data obtained from DNA array hybridization
      experiments. Most of the existing approaches to clustering use (normalized) real
      intensity values and thus do not treat positive and negative hybridization
      signals equally (positive signals are much more emphasized). In this paper, we
      consider a discrete approach. Fingerprint data are first normalized and binarized
      using control DNA clones. Because there may exist unresolved (or missing) values
      in this binarization process, we formulate the clustering of (binary)
      oligonucleotide fingerprints as a combinatorial optimization problem that
      attempts to identify clusters and resolve the missing values in the fingerprints
      simultaneously. We study the computational complexity of this clustering problem
      and a natural parameterized version, and present an efficient greedy algorithm
      based on MINIMUM CLIQUE PARTITION on graphs. The algorithm takes advantage of
      some unique properties of the graphs considered here, which allow us to
      efficiently find the maximum cliques as well as some special maximal cliques. Our
      experimental results on simulated and real data demonstrate that the algorithm
      runs faster and performs better than some popular hierarchical and graph-based
      clustering methods. The results on real data from DNA clone classification also
      suggest that this discrete approach is more accurate than clustering methods
      based on real intensity values, in terms of separating clones that have different
      characteristics with respect to the given oligonucleotide probes.

PMID- 16452778
TI  - Clustering time-varying gene expression profiles using scale-space signals.
AB  - The functional state of an organism is determined largely by the pattern of
      expression of its genes. The analysis of gene expression data from gene chips has
      primarily revolved around clustering and classification of the data using machine
      learning techniques based on the intensity of expression alone with the time
      varying pattern mostly ignored. In this paper, we present a pattern recognition
      based approach to capturing similarity by finding salient changes in the time
      varying expression patterns of genes. Such changes can give clues about important
      events, such as gene regulation by cell-cycle phases, or even signal the onset of
      a disease. Specifically, we observe that dissimilarity between time series is
      revealed by the sharp twists and bends produced in a higher-dimensional curve
      formed from the constituent signals. Scale-space analysis is used to detect the
      sharp twists and turns and their relative strength with respect to the component
      signals is estimated to form a shape similarity measure between time profiles. A
      clustering algorithm is presented to cluster gene profiles using the scale-space
      distance as a similarity metric. Multi-dimensional curves formed from time series
      within clusters are used as cluster prototypes or indexes to the gene expression
      database, and are used to retrieve the functionally similar genes to a query gene
      profile. Extensive comparison of clustering using scale-space distance in
      comparison to traditional Euclidean distance is presented on the yeast genome
      database.

PMID- 16452779
TI  - Fast and sensitive probe selection for DNA chips using jumps in matching
      statistics.
AB  - The design of large scale DNA microarrays is a challenging problem. So far, probe
      selection algorithms must trade the ability to cope with large scale problems for
      a loss of accuracy in the estimation of probe quality. We present an approach
      based on jumps in matching statistics that combines the best of both worlds. This
      article consists of two parts. The first part is theoretical. We introduce the
      notion of jumps in matching statistics between two strings and derive their
      properties. We estimate the frequency of jumps for random strings in a non
      uniform Bernoulli model and present a new heuristic argument to find the center
      of the length distribution of the longest substring that two random strings have
      in common. The results are generalized to near-perfect matches with a small
      number of mismatches. In the second part, we use the concept of jumps to improve
      the accuracy of the longest common factor approach for probe selection by moving
      from a string-based to an energy-based specificity measure, while only slightly
      more than doubling the selection time.

PMID- 16452781
TI  - Degenerate primer design via clustering.
AB  - This paper describes a new strategy for designing degenerate primers for a given
      multiple alignment of amino acid sequences. Degenerate primers are useful for
      amplifying homologous genes. However, when a large collection of sequences is
      considered, no consensus region may exist in the multiple alignment, making it
      impossible to design a single pair of primers for the collection. In such cases,
      manual methods are used to find smaller groups from the input collection so that
      primers can be designed for individual groups. Our strategy proposes an automatic
      grouping of the input sequences by using clustering techniques. Conserved regions
      are then detected for each individual group. Conserved regions are scored using a
      BlockSimilarity score, a novel alignment scoring scheme that is appropriate for
      this application. Degenerate primers are then designed by reverse translating the
      conserved amino acid sequences to the corresponding nucleotide sequences. Our
      program, DePiCt, was written in BioPerl and was tested on the Toll-Interleukin
      Receptor (TIR)and the non-TIR family of plant resistance genes. Existing programs
      for degenerate primer design were unable to find primers for these data sets.

PMID- 16452780
TI  - Fast and accurate probe selection algorithm for large genomes.
AB  - The oligo microarray (DNA chip) technology in recent years has a significant
      impact on genomic study. Many fields such as gene discovery, drug discovery,
      toxicological research and disease diagnosis, will certainly benefit from its
      use. A microarray is an orderly arrangement of thousands of DNA fragments where
      each DNA fragment is a probe (or a fingerprint) of a gene/cDNA. It is important
      that each probe must uniquely associate with a particular gene/cDNA. Otherwise,
      the performance of the microarray will be affected. Existing algorithms usually
      select probes using the criteria of homogeneity, sensitivity, and specificity.
      Moreover, they improve efficiency employing some heuristics. Such approaches
      reduce the accuracy. Instead, we make use of some smart filtering techniques to
      avoid redundant computation while maintaining the accuracy. Based on the new
      algorithm, optimal short (20 bases) or long (50 or 70 bases) probes can be
      computed efficiently for large genomes.

PMID- 16452782
TI  - Group testing with DNA chips: generating designs and decoding experiments.
AB  - DNA microarrays are a valuable tool for massively parallel DNA-DNA hybridization
      experiments. Currently, most applications rely on the existence of sequence
      specific oligonucleotide probes. In large families of closely related target
      sequences, such as different virus subtypes, the high degree of similarity often
      makes it impossible to find a unique probe for every target. Fortunately, this is
      unnecessary. We propose a microarray design methodology based on a group testing
      approach. While probes might bind to multiple targets simultaneously, a properly
      chosen probe set can still unambiguously distinguish the presence of one target
      set from the presence of a different target set. Our method is the first one that
      explicitly takes cross-hybridization and experimental errors into account while
      accommodating several targets. The approach consists of three steps: (1) Pre
      selection of probe candidates, (2) Generation of a suitable group testing design,
      and (3) Decoding of hybridization results to infer presence or absence of
      individual targets. Our results show that this approach is very promising, even
      for challenging data sets and experimental error rates of up to 5%. On a data set
      of 28S rDNA sequences we were able to identify 660 sequences, a substantial
      improvement over a prior approach using unique probes which only identified 408
      sequences.

PMID- 16452783
TI  - Can we identify cellular pathways implicated in cancer using gene expression
      data?
AB  - The cancer state of a cell is characterized by alterations of important cellular
      processes such as cell proliferation, apoptosis, DNA-damage repair, etc. The
      expression of genes associated with cancer related pathways, therefore, may
      exhibit differences between the normal and the cancerous states. We explore
      various means to find these differences. We analyze 6 different pathways (p53,
      Ras, Brca, DNA damage repair, NFkappab and beta-catenin) and 4 different types of
      cancer: colon, pancreas, prostate and kidney. Our results are found to be mostly
      consistent with existing knowledge of the involvement of these pathways in
      different cancers. Our analysis constitutes proof of principle that it may be
      possible to predict the involvement of a particular pathway in cancer or other
      diseases by using gene expression data. Such method would be particularly useful
      for the types of diseases where biology is poorly understood.

PMID- 16452784
TI  - Combining microarrays and biological knowledge for estimating gene networks via
      Bayesian networks.
AB  - We propose a statistical method for estimating a gene network based on Bayesian
      networks from microarray gene expression data together with biological knowledge
      including protein-protein interactions, protein-DNA interactions, binding site
      information, existing literature and so on. Unfortunately, microarray data do not
      contain enough information for constructing gene networks accurately in many
      cases. Our method adds biological knowledge to the estimation method of gene
      networks under a Bayesian statistical framework, and also controls the trade-off
      between microarray information and biological knowledge automatically. We conduct
      Monte Carlo simulations to show the effectiveness of the proposed method. We
      analyze Saccharomyces cerevisiae gene expression data as an application.

PMID- 16452785
TI  - Two operative concepts for the post-genomic era: the "memoire vive" of the cell
      and a molecular algebra.
AB  - The first successes in cloning experiments and stem cell "reprogramming" have
      already demonstrated the primordial role of cellular working-space memory and
      regulatory mechanisms, which use the knowledge stored in the DNA database in read
      mode. We present an analogy between living systems and informatics systems by
      considering: 1) the cell cytoplasm as a memory device accessible as read/write;
      2) the mechanisms of regulation as a programming language defined by a grammar, a
      molecular algebra; 3) biological processes as volatile programs which are
      executed without being written; 4) DNA as a database in read only mode. We also
      present applications to two biological algorithms: the immune response and
      glycogen metabolism.

PMID- 16452786
TI  - Stochastic stage-structured modeling of the adaptive immune system.
AB  - We have constructed a computer model of the cytotoxic T lymphocyte (CTL) response
      to antigen and the maintenance of immunological memory. Because immune responses
      often begin with small numbers of cells and there is great variation among
      individual immune systems, we have chosen to implement a stochastic model that
      captures the life cycle of T cells more faithfully than deterministic models.
      Past models of the immune response have been differential equation based, which
      do not capture stochastic effects, or agent-based, which are computationally
      expensive. We use a stochastic stage-structured approach that has many of the
      advantages of agent-based modeling but is much more efficient. Our model can
      provide insights into the effect infections have on the CTL repertoire and the
      response to subsequent infections.

PMID- 16452787
TI  - A personalized and automated dbSNP surveillance system.
AB  - The development of high throughput techniques and large-scale studies in the
      biological sciences has given rise to an explosive growth in both the volume and
      types of data available to researchers. A surveillance system that monitors data
      repositories and reports changes helps manage the data overload. We developed a
      dbSNP surveillance system (URL:
      http://www.pharmgkb.org/do/serve?id=tools.surveillance.dbsnp) that performs
      surveillance on the dbSNP database and alerts users to new information. The
      system is notable because it is personalized and fully automated. Each registered
      user has a list of genes to follow and receives notification of new entries
      concerning these genes. The system integrates data from dbSNP, LocusLink,
      PharmGKB, and Genbank to position SNPs on reference sequences and classify SNPs
      into categories such as synonymous and non-synonymous SNPs. The system uses data
      warehousing, object model-based data integration, object-oriented programming,
      and a platform-neutral data access mechanism.

PMID- 16452788
TI  - Fourier harmonic approach for visualizing temporal patterns of gene expression
      data.
AB  - DNA microarray technology provides a broad snapshot of the state of the cell by
      measuring the expression levels of thousands of genes simultaneously.
      Visualization techniques can enable the exploration and detection of patterns and
      relationships in a complex dataset by presenting the data in a graphical format
      in which the key characteristics become more apparent. The purpose of this study
      is to present an interactive visualization technique conveying the temporal
      patterns of gene expression data in a form intuitive for non-specialized end
      users. The first Fourier harmonic projection (FFHP) was introduced to translate
      the multi-dimensional time series data into a two dimensional scatter plot. The
      spatial relationship of the points reflect the structure of the original dataset
      and relationships among clusters become two dimensional. The proposed method was
      tested using two published, array-derived gene expression datasets. Our results
      demonstrate the effectiveness of the approach.

PMID- 16452789
TI  - Towards index-based similarity search for protein structure databases.
AB  - We propose two methods for finding similarities in protein structure databases.
      Our techniques extract feature vectors on triplets of SSEs (Secondary Structure
      Elements) of proteins. These feature vectors are then indexed using a
      multidimensional index structure. Our first technique considers the problem of
      finding proteins similar to a given query protein in a protein dataset. This
      technique quickly finds promising proteins using the index structure. These
      proteins are then aligned to the query protein using a popular pairwise alignment
      tool such as VAST. We also develop a novel statistical model to estimate the
      goodness of a match using the SSEs. Our second technique considers the problem of
      joining two protein datasets to find an all-to-all similarity. Experimental
      results show that our techniques improve the pruning time of VAST 3 to 3.5 times
      while keeping the sensitivity similar.

PMID- 16452790
TI  - Local similarity in RNA secondary structures.
AB  - We present a systematic treatment of alignment distance and local similarity
      algorithms on trees and forests. We build upon the tree alignment algorithm for
      ordered trees given by Jiang et. al (1995) and extend it to calculate local
      forest alignments, which is essential for finding local similar regions in RNA
      secondary structures. The time complexity of our algorithm is O(|F(1)| |F(2)
      deg(F(1)) deg(F(2)) (deg(F(1)) + deg(F(2))) where |F(i)| is the number of nodes
      in forest F(i) and deg (F(i)) is the degree of F(i). We provide carefully
      engineered dynamic programming implementations using dense, two-dimensional
      tables which considerably reduces the space requirement. We suggest a new
      representation of RNA secondary structures as forests that allow reasonable
      scoring of edit operations on RNA secondary structures. The comparison of RNA
      secondary structures is facilitated by a new visualization technique for RNA
      secondary structure alignments. Finally, we show how potential regulatory motifs
      can be discovered solely by their structural preservation, and independent of
      their sequence conservation and position.

PMID- 16452791
TI  - CTSS: a robust and efficient method for protein structure alignment based on
      local geometrical and biological features.
AB  - We present a new method for conducting protein structure similarity searches,
      which improves on the accuracy, robustness, and efficiency of some existing
      techniques. Our method is grounded in the theory of differential geometry on 3D
      space curve matching. We generate shape signatures for proteins that are
      invariant, localized, robust, compact, and biologically meaningful. To improve
      matching accuracy, we smooth the noisy raw atomic coordinate data with spline
      fitting. To improve matching efficiency, we adopt a hierarchical coarse-to-fine
      strategy. We use an efficient hashing-based technique to screen out unlikely
      candidates and perform detailed pairwise alignments only for a small number of
      candidates that survive the screening process. Contrary to other hashing based
      techniques, our technique employs domain specific information (not just geometric
      information) in constructing the hash key, and hence, is more tuned to the domain
      of biology. Furthermore, the invariancy, localization, and compactness of the
      shape signatures allow us to utilize a well-known local sequence alignment
      algorithm for aligning two protein structures. One measure of the efficacy of the
      proposed technique is that we were able to discover new, meaningful motifs that
      were not reported by other structure alignment methods.

PMID- 16452792
TI  - Statistical and visual morph movie analysis of crystallographic mutant selection
      bias in protein mutation resource data.
AB  - The relationship between protein mutations and conformational change can
      potentially decipher the language relating sequence to structure. Elsewhere, we
      presented the Protein Mutant Resource (PMR), an online tool that systematically
      identified related mutants in the Protein DataBank (PDB), inferred mutant Gene
      Ontology classifications using data-mining, and allowed intuitive exploration of
      relationships between mutant structures. Here, we perform a comprehensive
      statistical analysis of PMR mutants. Although the PMR contains spectacular
      conformational changes, generally there is a counter-intuitive inverse
      relationship between conformational change and the number of mutations. That is,
      PDB mutations contrast naturally evolved mutations. We compare the frequencies of
      mutations in the PMR/PDB datasets against the PAM250 natural mutation frequencies
      to confirm this. We make available morph movies from PMR structure pairs,
      allowing visual analysis of conformational change and the ability to distinguish
      visually between conformational change due to motions (e.g., ligand binding)and
      mutations. The PMR is at http://pmr.sdsc.edu.

PMID- 16452793
TI  - Statistical inference for well-ordered structures in nucleotide sequences.
AB  - Distinct, local structures are frequently correlated with functional RNA elements
      involved in post-transcriptional regulation of gene expression. Discovery of
      microRNAs (miRNAs) suggests that there are a large class of small non-coding RNAs
      in eukaryotic genomes. These miRNAs have the potential to form distinct fold-back
      stem-loop structures. The prediction of those well-ordered folding sequences
      (WFS) in genomic sequences is very helpful for our understanding of RNA-based
      gene regulation and the determination of local RNA elements with structure
      dependent functions. In this study, we describe a novel method for discovering
      the local WFS in a nucleotide sequence by Monte Carlo simulation and RNA folding.
      In the approach the quality of a local WFS is assessed by the energy difference
      (E(diff)) between the optimal structure folded in the local segment and its
      corresponding optimal, restrained structure where all the previous base pairings
      formed in the optimal structure are prohibited. Distinct WFS can be discovered by
      scanning successive segments along a sequence for evaluating the difference
      between E(diff) of the natural sequence and those computed from randomly shuffled
      sequences. Our results indicate that the statistically significant WFS detected
      in the genomic sequences of Caenorhabditis elegans (C.elegans) F49E12, T07C5,
      T07D1, T10H9, Y56A3A and Y71G12B are coincident with known fold-back stem-loops
      found in miRNA precursors. The potential and implications of our method in
      searching for miRNAs in genomes is discussed.

PMID- 16452794
TI  - Automated protein NMR resonance assignments.
AB  - NMR resonance peak assignment is one of the key steps in solving an NMR protein
      structure. The assignment process links resonance peaks to individual residues of
      the target protein sequence, providing the prerequisite for establishing intra-
      and inter-residue spatial relationships between atoms. The assignment process is
      tedious and time-consuming, which could take many weeks. Though there exist a
      number of computer programs to assist the assignment process, many NMR labs are
      still doing the assignments manually to ensure quality. This paper presents (1) a
      new scoring system for mapping spin systems to residues, (2) an automated
      adjacency information extraction procedure from NMR spectra, and (3) a very fast
      assignment algorithm based on our previous proposed greedy filtering method and a
      maximum matching algorithm to automate the assignment process. The computational
      tests on 70 instances of (pseudo) experimental NMR data of 14 proteins
      demonstrate that the new score scheme has much better discerning power with the
      aid of adjacency information between spin systems simulated across various NMR
      spectra. Typically, with automated extraction of adjacency information, our
      method achieves nearly complete assignments for most of the proteins. The
      experiment shows very promising perspective that the fast automated assignment
      algorithm together with the new score scheme and automated adjacency extraction
      may be ready for practical use.

PMID- 16452795
TI  - 3D structural homology detection via unassigned residual dipolar couplings.
AB  - Recognition of a protein's fold provides valuable information about its function.
      While many sequence-based homology prediction methods exist, an important
      challenge remains: two highly dissimilar sequences can have similar folds-- how
      can we detect this rapidly, in the context of structural genomics? High
      throughput NMR experiments, coupled with novel algorithms for data analysis, can
      address this challenge. We report an automated procedure for detecting 3D
      structural homologies from sparse, unassigned protein NMR data. Our method
      identifies the 3D structural models in a protein structural database whose
      geometries best fit the unassigned experimental NMR data. It does not use
      sequence information and is thus not limited by sequence homology. The method can
      also be used to confirm or refute structural predictions made by other techniques
      such as protein threading or sequence homology. The algorithm runs in O(pnk(3))
      time, where p is the number of proteins in the database, n is the number of
      residues in the target protein, and k is the resolution of a rotation search. The
      method requires only uniform (15)N-labelling of the protein and processes
      unassigned H(N)-(15)N residual dipolar couplings, which can be acquired in a
      couple of hours. Our experiments on NMR data from 5 different proteins
      demonstrate that the method identifies closely related protein folds, despite low
      sequence homology between the target protein and the computed model.

PMID- 16452796
TI  - Discovering compact and highly discriminative features or feature combinations of
      drug activities using support vector machines.
AB  - Nowadays, high throughput experimental techniques make it feasible to examine and
      collect massive data at the molecular level. These data, typically mapped to a
      very high dimensional feature space, carry rich information about functionalities
      of certain chemical or biological entities and can be used to infer valuable
      knowledge for the purposes of classification and prediction. Typically, a small
      number of features or feature combinations may play determinant roles in
      functional discrimination. The identification of such features or feature
      combinations is of great importance. In this paper, we study the problem of
      discovering compact and highly discriminative features or feature combinations
      from a rich feature collection. We employ the support vector machine as the
      classification means and aim at finding compact feature combinations. Comparing
      to previous methods on feature selection, which identify features solely based on
      their individual roles in the classification, our method is able to identify
      minimal feature combinations that ultimately have determinant roles in a
      systematic fashion. Experimental study on drug activity data shows that our
      method can discover descriptors that are not necessarily significant individually
      but are most significant collectively.

PMID- 16452798
TI  - An SVM-based algorithm for identification of photosynthesis-specific genome
      features.
AB  - This paper presents a novel algorithm for identification and functional
      characterization of "key" genome features responsible for a particular
      biochemical process of interest. The central idea is that individual genome
      features are identified as "key" features if the discrimination accuracy between
      two classes of genomes with respect to a given biochemical process is
      sufficiently affected by the inclusion or exclusion of these features. In this
      paper, genome features are defined by high-resolution gene functions. The
      discrimination procedure utilizes the Support Vector Machine classification
      technique. The application to the oxygenic photosynthetic process resulted in 126
      highly confident candidate genome features. While many of these features are well
      known components in the oxygenic photosynthetic process, others are completely
      unknown, even including some hypothetical proteins. It is obvious that our
      algorithm is capable of discovering features related to a targeted biochemical
      process.

PMID- 16452797
TI  - Initial large-scale exploration of protein-protein interactions in human brain.
AB  - Study of protein interaction networks is crucial to post-genomic systems biology.
      Aided by high-throughput screening technologies, biologists are rapidly
      accumulating protein-protein interaction data. Using a random yeast two-hybrid
      (R2H) process, we have performed large-scale yeast two-hybrid searches with
      approximately fifty thousand random human brain cDNA bait fragments against a
      human brain cDNA prey fragment library. From these searches, we have identified
      13,656 unique protein-protein interaction pairs involving 4,473 distinct known
      human loci. In this paper, we have performed our initial characterization of the
      protein interaction network in human brain tissue. We have classified and
      characterized all identified interactions based on Gene Ontology (GO) annotation
      of interacting loci. We have also described the "scale-free" topological
      structure of the network.

PMID- 16452799
TI  - Experimental studies of the Universal Chemical Key (UCK) algorithm on the NCI
      database of chemical compounds.
AB  - We have developed an algorithm called the Universal Chemical Key (UCK) algorithm
      that constructs a unique key for a molecular structure. The molecular structures
      are represented as undirected labeled graphs with the atoms representing the
      vertices of the graph and the bonds representing the edges. The algorithm was
      tested on 236,917 compounds obtained from the National Cancer Institute (NCI)
      database of chemical compounds. In this paper we present the algorithm,some
      examples and the experimental results on the NCI database. On the NCI database,
      the UCK algorithm provided distinct unique keys for chemicals with different
      molecular structures.

PMID- 16452800
TI  - A probabilistic model for identifying protein names and their name boundaries.
AB  - This paper proposes a method for identifying protein names in biomedical texts
      with an emphasis on detecting protein name boundaries. We use a probabilistic
      model which exploits several surface clues characterizing protein names and
      incorporates word classes for generalization. In contrast to previously proposed
      methods, our approach does not rely on natural language processing tools such as
      part-of-speech taggers and syntactic parsers, so as to reduce processing overhead
      and the potential number of probabilistic parameters to be estimated. A notion of
      certainty is also proposed to improve precision for identification. We
      implemented a protein name identification system based on our proposed method,
      and evaluated the system on real-world biomedical texts in conjunction with the
      previous work. The results showed that overall our system performs comparably to
      the state-of-the-art protein name identification system and that higher
      performance is achieved for compound names. In addition, it is demonstrated that
      our system can further improve precision by restricting the system output to
      those names with high certainties.

PMID- 16452801
TI  - cWINNOWER algorithm for finding fuzzy DNA motifs.
AB  - The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein
      binding signals. A signal is defined as any short nucleotide pattern having up to
      d mutations differing from a motif of length l. The algorithm finds such motifs
      if multiple mutated copies of the motif (i.e., the signals) are present in the
      DNA sequence in sufficient abundance. The cWINNOWER algorithm substantially
      improves the sensitivity of the winnower method of Pevzner and Sze by imposing a
      consensus constraint, enabling it to detect much weaker signals. We studied the
      minimum number of detectable motifs qc as a function of sequence length N for
      random sequences. We found that q(c) increases linearly with N for a fast version
      of the algorithm based on counting three-member sub-cliques. Imposing consensus
      constraints reduces q(c) by a factor of three in this case, which makes the
      algorithm dramatically more sensitive. Our most sensitive algorithm, which counts
      four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a
      sequence of length N = 12,000 for (l,d) = (15,4).

PMID- 16452802
TI  - LOGOS: a modular Bayesian model for de novo motif detection.
AB  - The complexity of the global organization and internal structures of motifs in
      higher eukaryotic organisms raises significant challenges for motif detection
      techniques. To achieve successful de novo motif detection it is necessary to
      model the complex dependencies within and among motifs and incorporate biological
      prior knowledge. In this paper, we present LOGOS, an integrated LOcal and GlObal
      motif Sequence model for biopolymer sequences, which provides a principled
      framework for developing, modularizing, extending and computing expressive motif
      models for complex biopolymer sequence analysis. LOGOS consists of two
      interacting submodels: HMDM, a local alignment model capturing biological prior
      knowledge and positional dependence within the motif local structure; and HMM, a
      global motif distribution model modeling frequencies and dependencies of motif
      occurrences. Model parameters can be fit using training motifs within an
      empirical Bayesian framework. A variational EM algorithm is developed for de novo
      motif detection. LOGOS improves over existing models that ignore biological
      priors and dependencies in motif structures and motif occurrences, and
      demonstrates superior performance on both semi-realistic test data and cis
      regulatory sequences from yeast and Drosophila sequences with regard to
      sensitivity, specificity, flexibility and extensibility.

PMID- 16452803
TI  - SMASHing regulatory sites in DNA by human-mouse sequence comparisons.
AB  - Regulatory sequence elements provide important clues to understanding and
      predicting gene expression. Although the binding sites for hundreds of
      transcription factors are known, there has been no systematic attempt to
      incorporate this information in the annotation of the human genome. Cross species
      sequence comparisons are critical to a meaningful annotation of regulatory
      elements since they generally reside in conserved non-coding regions. To take
      advantage of the recently completed drafts of the mouse and human genomes for
      annotating transcription factor binding sites, we developed SMASH, a
      computational pipeline that identifies thousands of orthologous human/ mouse
      proteins, maps them to genomic sequences, extracts and compares upstream regions
      and annotates putative regulatory elements in conserved, non-coding, upstream
      regions. Our current dataset consists of approximately 2,500 human/mouse gene
      pairs. Transcription start sites were estimated by mapping quasi-full length cDNA
      sequences. SMASH uses a novel probabilistic method to identify putative conserved
      binding sites that takes into account the competition between transcription
      factors for binding DNA. SMASH presents the results via a genome browser web
      interface which displays the predicted regulatory information together with the
      current annotations for the human genome. Our results are validated by comparison
      to previously published experimental data. SMASH results compare favorably to
      other existing computational approaches.

PMID- 16452804
TI  - A block coding method that leads to significantly lower entropy values for the
      proteins and coding sections of Haemophilus influenzae.
AB  - A simple statistical block code in combination with the LZW-based compression
      utilities gzip and compress has been found to increase by a significant amount
      the level of compression possible for the proteins encoded in Haemophilus
      influenzae, the first fully sequenced genome. The method yields an entropy value
      of 3.665 bits per symbol (bps), which is 0.657 bps below the maximum of 4.322 bps
      and an improvement of 0.452 bps over the best known to date of 4.118 bps using
      Matsumoto, Sadakane, and Imai's lza-CTW algorithm. Calculations based on a
      compact inverse genetic code show that the genome has a maximum entropy of 1.757
      bps for the coding regions, with a possibly lower actual entropy. These results
      hint at the existence of hitherto unexplored redundancies that do not show up in
      Markov models and are indicative of more internal structure than suspected in
      both the protein and the genome.

PMID- 16452805
TI  - A pattern matching algorithm for codon optimization and CpG motif-engineering in
      DNA expression vectors.
AB  - Codon optimization enhances the efficiency of DNA expression vectors used in DNA
      vaccination and gene therapy by increasing protein expression. Additionally,
      certain nucleotide motifs have experimentally been shown to be immuno-stimulatory
      while certain others immuno-suppressive. In this paper, we present algorithms to
      locate a given set of immuno-modulatory motifs in the DNA expression vectors
      corresponding to a given amino acid sequence and maximize or minimize the number
      and the context of the immuno-modulatory motifs in the DNA expression vectors.
      The main contribution is to use multiple pattern matching algorithms to
      synthesize a DNA sequence for a given amino acid sequence and a graph theoretic
      approach for finding the longest weighted path in a directed graph that will
      maximize or minimize certain motifs. This is achieved using O(n(2)) time, where n
      is the length of the amino acid sequence. Based on this, we develop a software
      tool.

PMID- 16452806
TI  - Haplotype motifs: an algorithmic approach to locating evolutionarily conserved
      patterns in haploid sequences.
AB  - The promise of plentiful data on common human genetic variations has given hope
      that we will be able to uncover genetic factors behind common diseases that have
      proven difficult to locate by prior methods. Much recent interest in this problem
      has focused on using haplotypes (contiguous regions of correlated genetic
      variations), instead of the isolated variations, in order to reduce the size of
      the statistical analysis problem. In order to most effectively use such variation
      data, we will need a better understanding of haplotype structure, including both
      the general principles underlying haplotype structure in the human population and
      the specific structures found in particular genetic regions or sub-populations.
      This paper presents a probabilistic model for analyzing haplotype structure in a
      population using conserved motifs found in statistically significant sub
      populations. It describes the model and computational methods for deriving the
      predicted motif set and haplotype structure for a population. It further presents
      results on simulated data, in order to validate the method, and on two real
      datasets from the literature, in order to illustrate its practical application.

PMID- 16452807
TI  - Computing highly specific and mismatch tolerant oligomers efficiently.
AB  - The sequencing of the genomes of a variety of species and the growing databases
      containing expressed sequence tags (ESTs) and complementary DNAs (cDNAs)
      facilitate the design of highly specific oligomers for use as genomic markers,
      PCR primers, or DNA oligo microarrays. The first step in evaluating the
      specificity of short oligomers of about twenty units in length is to determine
      the frequencies at which the oligomers occur. However, for oligomers longer than
      about fifty units this is not efficient, as they usually have a frequency of only
      1. A more suitable procedure is to consider the mismatch tolerance of an
      oligomer, that is, the minimum number of mismatches that allows a given oligomer
      to match a sub-sequence other than the target sequence anywhere in the genome or
      the EST database. However, calculating the exact value of mismatch tolerance is
      computationally costly and impractical. Therefore, we studied the problem of
      checking whether an oligomer meets the constraint that its mismatch tolerance is
      no less than a given threshold. Here, we present an efficient dynamic programming
      algorithm solution that utilizes suffix and height arrays. We demonstrated the
      effectiveness of this algorithm by efficiently computing a dense list of oligo
      markers applicable to the human genome. Experimental results show that the
      algorithm runs faster than well-known Abrahamson's algorithm by orders of
      magnitude and is able to enumerate 63% to approximately 79% of qualified
      oligomers.

PMID- 16452808
TI  - AntiClustal: Multiple Sequence Alignment by antipole clustering and linear
      approximate 1-median computation.
AB  - In this paper we present a new Multiple Sequence Alignment (MSA) algorithm called
      AntiClusAl. The method makes use of the commonly use idea of aligning homologous
      sequences belonging to classes generated by some clustering algorithm, and then
      continue the alignment process ina bottom-up way along a suitable tree structure.
      The final result is then read at the root of the tree. Multiple sequence
      alignment in each cluster makes use of the progressive alignment with the 1
      median (center) of the cluster. The 1-median of set S of sequences is the element
      of S which minimizes the average distance from any other sequence in S. Its exact
      computation requires quadratic time. The basic idea of our proposed algorithm is
      to make use of a simple and natural algorithmic technique based on randomized
      tournaments which has been successfully applied to large size search problems in
      general metric spaces. In particular a clustering algorithm called Antipole tree
      and an approximate linear 1-median computation are used. Our algorithm compared
      with Clustal W, a widely used tool to MSA, shows a better running time results
      with fully comparable alignment quality. A successful biological application
      showing high aminoacid conservation during evolution of Xenopus laevis SOD2 is
      also cited.

PMID- 16452809
TI  - Efficient constrained multiple sequence alignment with performance guarantee.
AB  - The Constrained Multiple Sequence Alignment problem is to align a set of
      sequences subject to a given constrained sequence, which arises from some
      knowledge of the structure of the sequences. This paper presents new algorithms
      for this problem, which are more efficient in terms of time and space (memory)
      than the previous algorithms [14], and with a worst-case guarantee on the quality
      of the alignment. Saving the space requirement by a quadratic factor is
      particularly significant as the previous O(n(4))-space algorithm has limited
      application due to its huge memory requirement. Experiments on real data sets
      confirm that our new algorithms show improvements in both alignment quality and
      resource requirements.

PMID- 16452810
TI  - A new similarity measure among protein sequences.
AB  - Protein sequence analysis is an important tool to decode the logic of life. One
      of the most important similarity measures in this area is the edit distance
      between amino acids of two sequences. We believe this criterion should be
      reconsidered because protein features are probably associated more with small
      peptide fragments than with individual amino acids. In this paper, we design
      small patterns that are associated with highly conversed regions among a set of
      protein sequences. These patterns are used analogous to the index terms in
      information retrieval. Therefore, we do not consider gaps within patterns. This
      new similarity measure has been applied to phylogenetic tree construction,
      protein clustering and protein secondary structure prediction and has produced
      promising results.

PMID- 16452811
TI  - A new approach for gene annotation using unambiguous sequence joining.
AB  - The problem addressed by this paper is accurate and automatic gene annotation
      following precise identification/ annotation of exon and intron boundaries of
      biologically verified nucleotide sequences using the alignment of human genomic
      DNA to curated mRNA transcripts. We provide a detailed description of a new
      cDNA/DNA homology gene annotation algorithm that combines the results of BLASTN
      searches and spliced alignments. Compared to other programs currently in use,
      annotation quality is significantly increased through the unambiguous junction of
      genomic DNA sequences. We also address gene annotation with both non-canonic
      splice sites and short exons. The approach has been tested on the Genie learning
      subset as well as full-scale human RefSeq, and has demonstrated performance as
      high as 97%.

PMID- 16452812
TI  - Efficient reconstruction of phylogenetic networks with constrained recombination.
AB  - A phylogenetic network is a generalization of a phylogenetic tree, allowing
      structural properties that are not tree-like. With the growth of genomic data,
      much of which does not fit ideal tree models, there is greater need to understand
      the algorithmics and combinatorics of phylogenetic networks [10, 11]. However, to
      date, very little has been published on this, with the notable exception of the
      paper by Wang et al.[12]. Other related papers include [4, 5, 7] We consider the
      problem introduced in [12], of determining whether the sequences can be derived
      on a phylogenetic network where the recombination cycles are node disjoint. In
      this paper, we call such a phylogenetic network a "galled-tree". By more deeply
      analysing the combinatorial constraints on cycle-disjoint phylogenetic networks,
      we obtain an efficient algorithm that is guaranteed to be both a necessary and
      sufficient test for the existence of a galled-tree for the data. If there is a
      galled-tree, the algorithm constructs one and obtains an implicit representation
      of all the galled trees for the data, and can create these in linear time for
      each one. We also note two additional results related to galled trees: first, any
      set of sequences that can be derived on a galled tree can be derived on a true
      tree (without recombination cycles), where at most one back mutation is allowed
      per site; second, the site compatibility problem (which is NP-hard in general)
      can be solved in linear time for any set of sequences that can be derived on a
      galled tree. The combinatorial constraints we develop apply (for the most part)
      to node-disjoint cycles in any phylogenetic network (not just galled-trees), and
      can be used for example to prove that a given site cannot be on a node-disjoint
      cycle in any phylogenetic network. Perhaps more important than the specific
      results about galled-trees, we introduce an approach that can be used to study
      recombination in phylogenetic networks that go beyond galled-trees.

PMID- 16452813
TI  - Prokaryote phylogeny without sequence alignment: from avoidance signature to
      composition distance.
AB  - A new and essentially simple method to reconstruct prokaryotic phylogenetic trees
      from their complete genome data without using sequence alignment is proposed. It
      is based on the appearance frequency of oligopeptides of a fixed length (up to K
      = 6) in their proteomes. This is a method without fine adjustment and choice of
      genes. It can incorporate the effect of lateral gene transfer to some extent and
      leads to results comparable with the bacteriologists' systematics as reflected in
      the latest 2001 edition of the Bergey's Manual of Systematic Bacteriology [1, 2].
      A key point in our approach is subtraction of a random background by using a
      Markovian model of order K - 1 from the composition vectors to highlight the
      shaping role of natural selection.

PMID- 16452814
TI  - [Organ preservation, multimodal radical tumor therapy and reduction of therapy
      related morbidity--development of diagnostics and therapy of endometrial
      carcinoma].
AB  - Endometrial carcinoma is the most frequent genital malignoma in women.
      Considering the tumor-biological and prognostically very different subtypes of
      endometrial carcinoma, an individual therapeutic strategy plays a very important
      role. Besides the question of an individualized organ-preserving procedure for
      women who wish to have a baby, the reduction of morbidity by minimally invasive
      laparoscopic/vaginal surgery is discussed. While adjuvant gestagen therapy is not
      useful, platinum-containing chemotherapy seems to be effective in certain risk
      situations. The indication of lymphonodectomy with regard to staging as well as
      the effect of adjuvant radiation therapy for local control are undisputed. In
      view of a postulated curative effect, the results of the ongoing prospective
      studies will make things clearer.

PMID- 16452815
TI  - Hysteroscopy and ultrasonography in the diagnosis of endometrial cancer.
AB  - The main aim of investigating women with abnormal uterine bleeding is to exclude
      serious intrauterine pathology, particularly endometrial cancer. Endometrial
      assessment has traditionally been achieved by obtaining tissue for histological
      analysis utilising blind in-patient dilatation of the cervix and curettage of the
      endometrium under general anaesthesia. This procedure is now generally accepted
      as outmoded practice associated with unnecessary morbidity and cost and has been
      largely replaced by minimally invasive out-patient or 'ambulatory' diagnostic
      modalities. These modalities include transvaginal ultrasonography, out-patient
      hysteroscopy and miniature endometrial biopsy. The most controversial debate has
      centred on how best to image the uterine cavity with advocates of hysteroscopy
      and ultrasonography holding apparently implacable views. However, the concept of
      hysteroscopy and ultrasonography as competing tests may be misplaced, and perhaps
      they should be viewed as complementary diagnostic tools. To help us answer such
      questions requires an appraisal of the available evidence. In this way, a more
      rational approach to investigating women for endometrial cancer is possible based
      on the clinical and economic performance of hysteroscopy and ultrasonography.
      This review assesses the evidence and suggests approaches available to
      gynaecologists for the diagnostic work-up of women suspected to have endometrial
      cancer utilising hysteroscopy and ultrasonography.

PMID- 16452817
TI  - Fertility-preserving treatment in young women with endometrial cancer.
AB  - Nonsurgical fertility-preserving treatment of well-differentiated endometrial
      cancer with systemic progestins has been described for young women who desire to
      preserve their fertility. The overall response to progestin treatment in 9
      retrospective studies is 79% with 79 subsequent live births. Recurrence can be
      expected in approximately 36-40% of conservatively treated patients who initially
      responded. Synchronous ovarian cancer has been reported in approximately 9%.
      However, amongst 162 receiving systemic, continuous treatment with progestins no
      death caused by cancer has been reported. We review guidelines for diagnosis,
      treatment and follow-up in young women undergoing conservative treatment for
      endometrial cancer.

PMID- 16452816
TI  - [Role of Laparoscopy in the Treatment of Endometrial Carcinoma].
AB  - In the treatment of endometrial carcinoma of stages I and II, laparoscopic or
      laparoscopically assisted vaginal hysterectomy with bilateral adnexectomy is
      oncologically equivalent to abdominal hysterectomy. As the pelvic and para-aortal
      laparoscopic lymph node dissection can now be safely carried out, it is possible
      to decide definitely for or against adjuvant percutaneous irradiation. The
      removal of metastatic lymph nodes seems to improve survival significantly.

PMID- 16452818
TI  - [The validity of chemotherapy in the treatment of endometrial cancer].
AB  - Endometrial cancer is a heterogeneous tumour with two types which can be
      distinguished clinically, histologically and pathogenetically:the classical
      endometrioid cancer (type 1) with a good prognosis and the aggressive
      histological type 2 with a poor prognosis and early metastatic spread. The most
      active cytotoxic drugs in advanced or metastatic endometrial cancer are the
      anthracyclines, the platinum salts and the taxanes. In most studies, combination
      chemotherapy is superior to monotherapy in terms of response rates. In the last
      few years there is growing evidence that chemotherapy can prolong overall
      survival in metastatic endometrial cancer and that adjuvant chemotherapy can
      reduce recurrence rates in high-risk situations.

PMID- 16452819
TI  - [Bulking agents and their place in the treatment of urinary stress incontinence].
AB  - Bulking agents are used in the treatment of urinary stress incontinence
      associated with intrinsic sphincter deficiency. Bovine collagen remains the gold
      standard despite problems such as allergic reaction and absorption of the
      injected material. Several new products are being evaluated or used clinically to
      try and overcome problems linked with bovine collagen. The aim of this paper is
      to review the bulking agents available and to put in prospect use of these
      products with the recent progress made in the treatment of urinary stress
      incontinence. The gold standard treatment for intrinsic sphincter deficiency is
      suburethral autologous or synthetic suburethral slings. Bulking agents are
      indicated for multi-operated patients with urinary stress incontinence and
      intrinsic sphincter deficiency. Bladder neck hypermobility is not a
      contraindication.

PMID- 16452820
TI  - [Prof. Urs Haller--an example of a picture book career. In honor of the
      extraordinary president of the Zurich University Gynecologic Clinic].

PMID- 16452821
TI  - [Recommendations for estrogen and progesterone replacement in climacteric and
      postmenopause. 33. Workshop of the "Zurich Discussion Circle", October 2004].

PMID- 16452823
TI  - [A practice guideline for diagnosis and treatment of ductal in situ carcinoma of
      the breast].

PMID- 16452822
TI  - [Recommendations for hormonal contraception. 34. Workshop of the "Zurich
      Discussion Circle", April 2005].

PMID- 16452824
TI  - [Sling operations for treatment of stress incontinence in the woman. Expert
      correspondence update (replaces the October 2003 version)].

PMID- 16452825
TI  - Mechanisms of UV-induced immunosuppression.
AB  - Ultraviolet radiation (UV), in particular the UVB range, suppresses the immune
      system in several ways. UVB inhibits antigen presentation, induces the release of
      immunosuppressive cytokines and causes apoptosis of leukocytes. UVB, however,
      does not cause general immunosuppression but rather inhibits immune reactions in
      an antigen-specific fashion. Application of contact allergens onto UV-exposed
      skin does not cause sensitization but induces antigen-specific tolerance since
      such an individual cannot be sensitized against the very same allergen later,
      although sensitization against other allergens is not impaired. This specific
      immunosuppression is mediated by antigen-specific suppressor/ regulatory T cells.
      UVB-induced DNA damage is a major molecular trigger of UV-mediated
      immunosuppression. Reduction of DNA damage mitigates UV-induced
      immunosuppression. Likewise interleukin-12 which exhibits the capacity to reduce
      DNA damage can prevent UV-induced immunosuppression and even break tolerance.
      Presentation of the antigen by UV-damaged Langerhans cells in the lymph nodes
      appears to be an essential requirement for the development of regulatory T cells.
      Studies addressing the molecular mechanisms underlying UV-induced
      immunosuppression will contribute to a better understanding how UV acts as a
      pathogen but on the other hand can be also used as a therapeutic tool.

PMID- 16452826
TI  - Prosthetically driven implant placement. How to achieve the appropriate implant
      site development.
AB  - Dental implants are established alternatives for replacing missing teeth. Tooth
      loss for different reasons may leads to alveolar resorption. Shortage of bone can
      prevent proper positioning of dental implants according to prosthetic needs and
      treatment planning, unless the volume of hard and soft tissues is increased
      before implantation. In the esthetic area it is essential not only to achieve
      well-anchored implants but also sufficient soft and hard tissue in order to
      obtain natural looking result. This article will present several treatment
      modalities to augment the soft and hard tissues in order to obtain proper
      insertion of implants according to prosthetic needs and patient satisfaction.

PMID- 16452827
TI  - U.S. practices for colon cancer screening.
AB  - As the prevalence of gastric carcinoma decreases in Japan, the prevalence of
      colon cancer has been increasing. Examination of the screening practices for
      colon cancer in the United States can offer insight into practices that may be
      useful in Japan. This paper will review the epidemiology and risk factors for
      colon cancer, the genetics of colon cancer, prevention issues, screening
      modalities, and current recommendations in U.S. practice.

PMID- 16452828
TI  - Apoptosis and lung injury.
AB  - Apoptosis is important in developmental biology and in remodeling of tissues
      during repair. Apoptosis also plays important roles in the progression of many
      diseases. The cellular and molecular mechanisms of apoptosis, in general, have
      been extensively demonstrated. However, the causes and the roles of apoptosis of
      various cell types in the lung are not well understood. We have determined that
      adenosine/homocysteine causes lung vascular endothelial cell apoptosis by
      inhibition of carboxyl methylation of the small GTPase, Ras, through inhibition
      of isoprenylcysteine carboxyl methyltransferase(ICMT) activity, leading to
      inactivation of Ras and the subsequent disruption of focal adhesion complexes,
      resulting in cell-extracellular matrix detachment and anoikis. Apoptosis can
      either ameliorate or exacerbate lung injury, depending upon the cell type.
      Although apoptosis of polymorphonuclear leukocytes in the lung prevents
      inflammation and the development of acute respiratory distress syndrome during
      acute lung injury, Fas/FasL-mediated alveolar epithelial cell apoptosis promotes
      acute lung injury and pulmonary fibrosis. Lung epithelial and endothelial cell
      apoptosis also contributes to the development of emphysema. This article focuses
      on elucidating the mechanisms of adenosine/homocysteine-induced endothelial cell
      apoptosis. We also review the current understanding of the role of lung cell
      apoptosis in acute lung injury, pulmonary fibrosis and emphysema.

PMID- 16452829
TI  - Fat paradox in liver disease.
AB  - Alcoholic liver disease (ALD) is characterized by accumulation of neutral lipids
      in hepatocytes leading to micro and macro-vesicular steatosis and balloon cell
      degeneration. Hypercaloric alimentation and resultant obesity also cause similar
      changes as evident in non-alcoholic fatty liver disease (NAFLD). Thus,
      accumulation of lipids in hepatocytes is a pathologic hallmark of ALD and NAFLD.
      In contrast, quiescent hepatic stellate cells (HSC) are characterized by the
      intracellular content of not only vitamin A but also triglycerides, and HSC
      activation is associated with depletion of these lipids. In fact, our recent work
      demonstrates that adipogenic/ lipogenic transcriptional regulation rendered by
      PPARgamma, LXRa, and SREBP-1c is essential for the maintenance of the fat
      storing, quiescence phenotype of HSC. Expression of these adipogenic
      transcription factors is lost in activated HSC and the treatment of the cells
      with the adipocyte differentiation cocktail or ectopic expression of PPARgamma or
      SREBP-1c causes a reversal of activated cells to the quiescent phenotype. In
      steatotic livers from ALD and NAFLD mouse models, the expression of these
      adipogenic transcription factors is induced while the normal control livers lack
      such expression. Thus, adipogenic regulation is essential for HSC quiescence
      while it makes hepatocytes steatotic. Interestingly, under the adipogenic
      conditions of ALD and NAFLD, HSC are still activated to cause fibrosis. This fat
      paradox in hepatocytes and HSC highlights contrasted significance of fat in these
      two cell types that depend on each other for their homeostatic control. It
      further suggests, activated HSC in steatotic livers may have defective insulin
      signaling or lipogenic regulation.

PMID- 16452830
TI  - Clinical electromyography and electrodiagnosis course at Keio University Hospital
      -a 7-year experience.
AB  - Although electromyography and electrodiagnosis (EMG-EDX) is one of the most
      fundamental skills in rehabilitation medicine, the number of residency programs
      that can provide comprehensive postgraduate EMG-EDX training is still limited in
      Japan. Under these circumstances, we started a 2-day primer course in EMG-EDX at
      Keio University Hospital in 1998. To review our 7-year experience with the
      course, we analyzed the number and specialty of the participants, their appraisal
      of the lectures and practical sessions, and the score distribution of the final
      examination. The number of participants totaled 288 during the past 7 years, and
      the mean number for each year was 41. The distribution by specialty for the whole
      period was 64.0% for rehabilitation medicine, 25.4% for orthopedic surgery, 5.1%
      for neurology, 1.0% for pediatrics, 0.5% for gerontology and 4.1% for physical
      therapists and occupational therapists. The difficulty levels of the lectures
      were judged as appropriate by 81 to 95.5% of the participants, and the
      presentation was judged as good by 34 to 67% of them. For the practice sessions,
      the difficulty levels were judged as appropriate by 88% of the participants, and
      the quality of the supervisors was judged as good by 64% of them. The mean score
      for the final examination was 56.0 (SD 15.2, median 60). In conclusion, our
      course has played an important role to promote EMG-EDX in our country by
      providing compact introductory exposure to EMG-EDX for beginners. A follow-up
      system for the course graduates is planned to support their EMG-EDX practice.

PMID- 16452831
TI  - Evidence-based overview of ophthalmic disorders in deaf children: a literature
      update.
AB  - BACKGROUND: Deaf children are heavily reliant on the sense of vision in order to
      develop efficient communication skills and explore the world around them. Any
      ophthalmic disorder may thus negatively impact on this process, especially if it
      is unrecognised in the early years of life. These disorders may be correctable
      (such as myopia) or treatable (such as cataract), and their early identification
      is of the utmost importance to optimise language development (spoken or sign, or
      both) and develop social cognition. Those children with non-correctable and non
      treatable visual disorders, like retinitis pigmentosa in Usher syndrome, require
      multiple environmental adaptations and appropriate support services and
      information. AIM: : To review the accumulated scientific knowledge on ophthalmic
      disorders in deaf children and assess the quality of evidence published in the
      literature in order to contribute to better diagnosis and management of these
      conditions. MATERIAL AND METHODS: The project reviewed more than 1000 published
      papers and other sources. 191 papers complied with the aims of the study and were
      used in the project. From these studies, 95% were based on type III or IV
      evidence (mainly descriptive studies or case reports). Only 3% were based on type
      II evidence and 2% on type I evidence. RESULTS-CONCLUSIONS: The main conclusions
      of this project are: a) the overall quality of evidence in the literature
      concerning deaf children and their ophthalmic problems is very low, b) the
      prevalence of ophthalmic problems in deaf children is very high (approximately
      40% to 60%) and these problems may remain undetected for years although they may
      have a serious impact on children's acquisition of communication skills, c)
      screening for ophthalmic problems in deaf children should be encouraged and
      specialist ophthalmic examination should be carried out as soon as the diagnosis
      of deafness is confirmed irrespective of age, and may need to be repeated at
      intervals following diagnosis, d) families should be informed about the nature of
      the screening process in discussion with the relevant professionals and
      appropriate information should be available in a range of formats and in
      different community languages, e) professionals administering the tests should be
      familiar with the needs of deaf children with ophthalmic problems and should be
      sensitive to the communication needs of the child, especially undertaking
      behavioural testing where their collaboration is needed, f) while orthoptists can
      perform the majority of psychophysical tests (visual and stereo acuity tests,
      ocular motility tests, etc.) a comprehensive opthalmologic assessment by slit
      lamp biomicroscopy, streak retinoscopy, direct and indirect ophthalmoscopy,
      intraocular pressure measurement etc is required. Electrophysiologic testing to
      help identification of Usher syndrome may also be required, and finally g) serial
      hearing assessments of children with dual sensory deficits are needed to monitor
      hearing thresholds, to optimise hearing aid use and to ensure timely referral for
      cochlear implantation for those who need it.

PMID- 16452832
TI  - Pendimethalin exposure and cancer incidence among pesticide applicators.
AB  - BACKGROUND: Pendimethalin, a widely used herbicide, has been classified as a
      group C possible human carcinogen by the U.S. Environmental Protection Agency. We
      evaluated the incidence of cancer in relation to reported pendimethelin use among
      pesticide applicators in the Agricultural Health Study, a prospective cohort of
      licensed pesticide applicators in Iowa and North Carolina. METHODS: Information
      on pesticide use came from two questionnaires (enrollment and take-home). The
      present analysis includes 9089 pendimethalin-exposed and 15,285 nonpendimethalin
      exposed pesticide applicators with complete information on pendimethalin use and
      covariates from a take-home questionnaire. We conducted Poisson regression
      analyses to evaluate the association of pendimethalin exposure with cancer
      incidence (mean follow-up = 7.5 years) using two exposure metrics: tertiles of
      lifetime days of exposure and tertiles of intensity-weighted lifetime days of
      exposure. RESULTS: Overall cancer incidence did not increase with increasing
      lifetime pendimethalin use, and there was no clear evidence of an association
      between pendimethalin use and risks for specific cancers. The risk for rectal
      cancer rose with increasing lifetime pendimethalin exposure when using nonexposed
      as the reference (rate ratio = 4.3; 95% confidence interval = 1.5-12.7 for the
      highest exposed subjects; P for trend = 0.007), but the association was
      attenuated when using the low exposed as the referent group (P for trend = 0.08).
      Similar patterns for rectal cancer were observed when using intensity-weighted
      exposure-days. The number of rectal cancer cases among the pendimethalin-exposed
      was small (n = 19). There was some evidence for an elevated risk for lung cancer,
      but the excess occurred only in the highest exposure category for lifetime
      pendimethalin exposure. The trends for lung cancer risk were inconsistent for
      different exposure metrics. CONCLUSIONS: We did not find a clear association of
      lifetime pendimethalin exposure either with overall cancer incidence or with
      specific cancer sites.

PMID- 16452833
TI  - The mother as source of Helicobacter pylori infection.
AB  - BACKGROUND: To further elucidate the intrafamilial transmission of Helicobacter
      pylori infection, we investigated the occurrence of infection by parental
      infection status in a large community-based birth cohort of children from
      Germany. METHODS: Parental infection (at birth) and children's infection (at age
      3 years) were determined by C-urea breath test and by monoclonal antigen stool
      test. RESULTS: Twenty of 834 children (2.4%) were found to be infected. The odds
      ratio for H. pylori infection of the child was 12.9 (95% confidence interval =
      3.2-52.5) if the mother was infected and 1.4 (0.4-4.6) if the father was
      infected, after adjustment for infection status of the other parent and for
      nationality. The number of older siblings was not a risk factor for H. pylori
      infection of the child. CONCLUSIONS: This longitudinal study suggests that
      infected mothers are the main source of H. pylori infection of their children.

PMID- 16452834
TI  - Human papillomavirus (HPV) detection among human immunodeficiency virus-infected
      pregnant Thai women: implications for future HPV immunization.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected women are at increased
      risk for developing cervical cancer and for infection with human papillomavirus
      (HPV). Prophylactic vaccines targeting HPV types 16 and 18 are being evaluated
      for efficacy among young women. GOAL: The goal was to assess the prevalence of
      HPV among HIV-infected pregnant women in Bangkok and to evaluate the need for
      prophylactic HPV vaccines studies in this population. STUDY DESIGN: The study
      population consisted of 256 HIV-infected pregnant women who participated in a
      mother-to-child HIV transmission trial. Stored cervicovaginal lavage samples were
      tested for the presence of HPV DNA by polymerase chain reaction with PGMY09/11
      primers and reverse line-blot hybridization for determination of anogenital HPV
      types. RESULTS: HPV prevalence was 35.5% (91/256); high-risk HPV prevalence was
      23.4% (60/256). HPV type 16 or 18 was present in 8.2% (21/256). Almost half of
      all infections were multiple. Furthermore, overall HPV detection was associated
      with abnormal cervical cytology (P<0.001) and higher HIV-plasma viral load
      (P=0.007). CONCLUSIONS: Only one-quarter of HIV-infected pregnant women in
      Bangkok had high-risk HPV types; less than 10% had HPV types 16 or 18. As the HPV
      prevalence is expected to increase during HIV disease, prophylactic vaccines
      targeting HPV types 16 and 18 should be studied among HIV-infected women not yet
      infected with these HPV types and not previously exposed.

PMID- 16452835
TI  - Serious play. Skills learned in pediatrics are not just for the care of children.

PMID- 16452836
TI  - I am not a male nurse. Recruiting efforts may reinforce a stereotype.

PMID- 16452838
TI  - Heroic nurses.

PMID- 16452839
TI  - Artistic license?

PMID- 16452840
TI  - License renewal.

PMID- 16452841
TI  - Pain assessment.

PMID- 16452842
TI  - London nurses.

PMID- 16452843
TI  - CMAs.

PMID- 16452849
TI  - Men in nursing: still too few. Discrimination and stereotypes still keep many
      from joining nursing ranks.

PMID- 16452851
TI  - The 2005 White House Conference on Aging. Real policymaking--or rubber stamping?

PMID- 16452853
TI  - The eyes of a pediatric nurse. Could lessons learned from children apply to
      adults?

PMID- 16452854
TI  - Endocarditis after valve replacement surgery. Early recognition and treatment are
      essential to averting deadly complications.
AB  - The incidence of infective endocarditis, an inflammation of the heart valves, the
      endocardium, or both that's caused by bacterial, viral, or fungal agents,
      continues to rise despite advances in treatment. People with prosthetic valves
      are among those at highest risk, and mortality rates can be extremely high,
      especially in cases of early onset. Diagnosis is challenging, in part because
      signs and symptoms associated with systemic infections can mask signs of the
      underlying endocarditis. This article outlines the causes and effects of
      prosthetic valve-related endocarditis (PVE), describes its signs and symptoms,
      discusses the leading diagnostic tests and criteria, and addresses prevention and
      treatment, as well as nursing implications.

PMID- 16452857
TI  - Placebo: no relief for Ms. Mahoney's pain. Working with the patient, family, and
      staff to diminish pain.

PMID- 16452858
TI  - The clinical use of placebos. Is it ethical? Not when it involves deceiving
      patients.

PMID- 16452859
TI  - The debate over placebos in pain management. The ASPMN disagrees with a recent
      placebo position statement.

PMID- 16452863
TI  - Are you the best leader you can be?

PMID- 16452864
TI  - From classroom to Congress. My year on the legislative staff of the U.S. Senate.

PMID- 16452875
TI  - It's in the genes. The ANA and nurse leaders want RNs and students to practice
      with genetics and genomics in mind.

PMID- 16452878
TI  - Missed dreams. RN helps wounded soldiers to set and reach their goals.

PMID- 16452879
TI  - Respiratory protection, part 2. When and how to protect yourself.

PMID- 16452880
TI  - If you're happy and you know it...

PMID- 16452883
TI  - Grasping the concept of medical futility.

PMID- 16452884
TI  - Ground instability with mentoring.

PMID- 16452886
TI  - Nursing practice violations: what's your response?

PMID- 16452887
TI  - Are you the best leader you can be?

PMID- 16452888
TI  - RFID: bar coding's replacement?

PMID- 16452889
TI  - Open new care pathways with drug-eluting stents.

PMID- 16452892
TI  - Get "wired" for clinical excellence.

PMID- 16452891
TI  - See the future of distance education.

PMID- 16452893
TI  - Succession planning.

PMID- 16452894
TI  - Nurse managed health centers: strengthening the healthcare safety net.

PMID- 16452895
TI  - Who, if not you, will determine NP scope of practice?

PMID- 16452897
TI  - Psychological and physical etiologies of heart palpitations.

PMID- 16452896
TI  - Skills taught in acute care NP programs: a national survey.

PMID- 16452901
TI  - Osteoporosis: new options for pain relief.

PMID- 16452902
TI  - Depression and alcohol abuse in asthmatic college students.

PMID- 16452899
TI  - A look back at the most influential drug approvals of 2005.

PMID- 16452904
TI  - Medicare part D prescription drug benefit--part 1 of 2.

PMID- 16452903
TI  - Recommendations for assessing insomnia.

PMID- 16452905
TI  - Proposed screening recommendations for male breast cancer.

PMID- 16452910
TI  - Assessment of carotenoid status and the relation to glycaemic control in type I
      diabetics: a follow-up study.
AB  - OBJECTIVE: To assess the carotenoid status in young type I diabetic patients and
      its relationship to the glycaemic control of the disease. DESIGN: A follow-up
      study. SETTING: Hospital Universitario Puerta de Hierro, Health Area VI of Madrid
      (Spain). SUBJECTS: Forty-seven type I diabetic patients, followed for 2.5 years.
      INTERVENTIONS: Coinciding with physical examination and laboratory tests, serum
      levels of carotenoids were analysed by HPLC, and dietary intake of carotenoids
      was evaluated by a semiquantitative food frequency questionnaire and 3-day
      prospective dietary records. RESULTS: In type I diabetic patients, average
      intake, serum levels and correlations between diet and serum levels of
      carotenoids were comparable to those in reference non-diabetic groups. Between
      subjects seasonal variations were observed for beta-cryptoxanthin intake and
      serum levels (higher in winter) and serum lycopene (higher in summer).
      Significant within-subjects seasonal changes were shown for dietary and serum
      beta-cryptoxanthin and serum beta-carotene. Serum carotenoids were unrelated to
      glycaemic control markers. Subjects with clinically acceptable glycaemic control
      showed lower lycopene intake than those with unacceptable control. Intake of
      carotenoids did not explain variance in insulin dose, fasting glycaemia,
      fructosamine or HbA1c. With the exception of lycopene, serum carotenoids were
      predicted by dietary intake, but in no case by fasting glycaemia, HbA1c or
      fructosamine. CONCLUSION: In type I diabetic patients, serum carotenoid
      concentrations and their variance are determined by dietary intake patterns, and
      are unrelated to the glycaemic control of the disease, as assessed by biochemical
      markers.

PMID- 16452911
TI  - Energy expenditure in underweight chronic obstructive pulmonary disease patients
      before and during a physiotherapy programme.
AB  - OBJECTIVE: To investigate how total daily energy expenditure (TEE) changes when
      underweight patients with chronic obstructive pulmonary disease (COPD) enters a
      physiotherapy programme. DESIGN: Prospective intervention study. SETTING:
      Sahlgrenska University Hospital, Goteborg, Sweden. SUBJECTS: Fifteen patients
      with severe COPD and BMI<21 kg/m(2) were recruited consecutively at the
      outpatient COPD unit at the Department of Respiratory Medicine. Fourteen patients
      completed the whole study. INTERVENTION: TEE was assessed by the doubly labelled
      water method in a 2-week control period and during 2 weeks of physiotherapy.
      Energy intake was assessed using 7-day dietary record during control and
      physiotherapy period. RESULTS: Mean TEE during physiotherapy period was 500 kJ
      (6%) lower than during control period but the difference was not statistically
      significant. Ten of the 14 patients had lower and four had higher TEE. Mean
      energy intake during the physiotherapy period did not change from the control
      period (7700 vs 7600 kJ/day). CONCLUSIONS: Since underweight patients with COPD
      may show variable TEE during physiotherapy compared to a control period, an
      assessment of individual energy requirements is recommended.

PMID- 16452912
TI  - Zinc supplementation to HIV-1-infected pregnant women: effects on maternal
      anthropometry, viral load, and early mother-to-child transmission.
AB  - OBJECTIVE: To examine the effect of zinc supplementation to HIV-1-infected
      pregnant women on viral load, early mother-to-child transmission of HIV (MTCT),
      and wasting. DESIGN: Double-blind placebo-controlled randomized clinical trial.
      SETTING: Antenatal clinic in Dar es Salaam, Tanzania. SUBJECTS: Four hundred HIV
      1-infected pregnant women. METHODS: Women 12-27 weeks of gestation were randomly
      assigned to receive a daily oral dose of 25 mg zinc or placebo from the day of
      the first prenatal visit until 6 weeks postdelivery. Weight and mid-upper arm
      circumference (MUAC) were measured monthly. HIV status of the babies was assessed
      at birth and at 6 weeks postpartum. Viral load was assessed in a random sample of
      100 women at baseline and at the end of the study. RESULTS: Zinc had no effects
      on maternal viral load or early MTCT. Supplementation was related to a
      significant threefold increase in the risk of wasting (reaching a MUAC value <22
      cm) during an average 22 weeks of observation (RR=2.7, 95%CI=1.1, 6.4, P=0.03),
      and to a 4 mm decline in MUAC during the second trimester (P=0.02). CONCLUSIONS:
      Zinc supplementation to HIV-infected pregnant women offers no benefits on viral
      load or MTCT. The clinical relevance of an apparent decrease in MUAC associated
      with zinc supplementation is yet to be ascertained. These findings together with
      the lack of effect on fetal outcomes (reported previously) do not provide support
      for the addition of zinc supplements to the standard of prenatal care among HIV
      infected women.

PMID- 16452913
TI  - Lower limb fracture, cognitive impairment and risk of subsequent malnutrition: a
      prospective evaluation of dietary energy and protein intake on an orthopaedic
      ward.
AB  - OBJECTIVE: To report the dietary energy and protein intake of undernourished
      older adults (with and without cognitive impairment) admitted to hospital
      following a lower limb fracture and to determine whether dietary intakes met
      estimated requirements. DESIGN: An observational study of a sequential sample.
      SETTING: The orthopaedic ward of a South Australian metropolitan teaching
      hospital. SUBJECTS: Sixty-eight patients aged > or =70 years screened as
      undernourished and admitted to hospital following lower limb fracture (50%
      cognitively impaired) provided 3 to 5 days of dietary data. MAJOR OUTCOME
      METHODS: Dietary energy and protein intake. METHODS: Dietary assessment using
      plate waste methodology and snack record charts commenced within 6 days
      postinjury and continued for up to five consecutive days or until discharge.
      Estimated resting energy requirements were calculated and adjusted for activity
      equivalent to bed rest and physiological stress. Protein requirements were
      calculated as 1 g/kg/day. Cognition was assessed using the Short Portable Mental
      Status Questionnaire. RESULTS: Cognitively impaired participants and those
      without cognitive impairment consumed, mean (95% CI) respectively, 3661 kJ/day
      (3201, 4121) versus 4208 kJ/day (3798, 4619) and 38 g (33, 44) versus 47 g (41,
      52) protein/day. Cognitively impaired participants consumed mean (95% CI) 48%
      (43, 53) of estimated total energy expenditure and 78% (69, 87) of estimated
      protein requirements. CONCLUSIONS: Orthopaedic fracture patients at greatest
      nutritional risk, including those with cognitive impairment, do not achieve
      estimated energy or protein requirements from diet alone. Effective methods of
      achieving requirements in this vulnerable group are needed before improvements in
      outcomes will be observed.

PMID- 16452914
TI  - 15N-excretion of heat-killed Lactobacillus casei in humans.
AB  - OBJECTIVE: In the present study, Lactobacillus casei (L. casei) labelled with 15N
      was used to follow the metabolic fate of orally administered heat-killed 15N
      labelled L. casei (15N-L.casei) in humans. DESIGN: Experimental study. SETTING:
      University of Rostock, Children's Hospital, Research Laboratory. SUBJECTS: Twelve
      healthy adults aged 23-32 years. INTERVENTION: The subjects received 36 mg/kg
      body weight heat-killed 15N-L.casei and 500 mg Lactose-[13C]ureide together with
      breakfast. Expired air samples were taken over 14 h, whereas urine and faeces
      were collected over 2 days. A blood sample was taken after 2 h. 13C- and 15N
      enrichments were measured by isotope ratio mass spectrometry (SerCon, UK).
      RESULTS: The orocaecal transit time (OCTT) was reached after 4.1 h. The urinary
      15N-excretion was 9.3% of the ingested dose, whereas the faecal excretion was
      65.1% of the ingested dose. After 2 h, 15N-enrichment of supernatant, fibrinogen,
      and plasma protein precipitate amounted to 254, 11, and 2 p.p.m. excess,
      respectively. CONCLUSIONS: In comparison to the OCTT of 4.1 h, 15N-enrichment in
      urinary ammonia and urinary total nitrogen already began to rise 30 min after 15N
      L.casei ingestion, indicating that 15N-L.casei is rapidly digested in the small
      bowel. This is confirmed by 15N-enrichments of blood plasma fractions. The
      ingestion of heat-killed 15N-L.casei led to a total excretion of 74.4% of the
      ingested 15N-dose.

PMID- 16452915
TI  - Public views of the benefits and barriers to the consumption of a plant-based
      diet.
AB  - OBJECTIVE: The aim of this study was to examine consumers' perceived benefits and
      barriers to the consumption of a plant-based diet. DESIGN: Mail survey that
      included questions on perceived benefits and barriers to the consumption of a
      plant-based diet. SETTING: Victoria, Australia. SUBJECTS: Four hundred and
      fifteen randomly selected Victorian adults. RESULTS: The main perceived barrier
      to adoption of a plant-based diet was a lack of information about plant-based
      diets (42% agreement). Sex, age and education differences were present in over a
      quarter of the barrier items. For example, non-university-educated respondents
      and older people were less willing to change their current eating pattern than
      were university educated and younger respondents. The main benefits associated
      with plant-based diets were health benefits, particularly decreased saturated fat
      intake (79% agreement), increased fibre intake (76%), and disease prevention
      (70%). Age, sex and education differences with regard to benefits were apparent,
      although sex differences were more important than age or education differences.
      CONCLUSIONS: The majority of respondents perceived there to be health benefits
      associated with the consumption of a plant-based diet. Compared with the
      proportion of respondents who agreed that there were particular benefits of
      eating a plant-based diet, perceived barriers were relatively low. An
      understanding of the perceived benefits and barriers of consuming a plant-based
      diet will help formulate strategies that aim to influence beliefs about plant
      foods, plant food consumption, and, ultimately, public health.

PMID- 16452916
TI  - Low-dietary fiber intake as a risk factor for recurrent abdominal pain in
      children.
AB  - OBJECTIVE: To evaluate dietary fiber intake in children with recurrent abdominal
      pain. DESIGN: Cross-sectional study with control group. SETTING: Outpatients of
      the Pediatric Gastroenterology public health clinic of the Darcy Vargas
      Children's Hospital, Brazil. SUBJECTS: Forty-one patients with recurrent
      abdominal pain were evaluated and 41 children, as a control group. INTERVENTIONS:
      Macronutrients and fiber intake evaluation by the Daily Food Intake method. Two
      tables of fiber composition in foods were used. RESULTS: According to the
      Brazilian table the mean intake of fiber (g/day) by the children of the recurrent
      abdominal pain groups with chronic constipation or not, and the control group
      was, respectively, 18.2, 16.6 and 23.7 for total fiber (P=0.001), 7.5, 6.9 and
      9.5 for soluble fiber (P=0.001) and 10.7, 9.7 and 14.1 for insoluble fiber
      (P=0.002). According to the AOAC table, the recurrent abdominal pain group with
      chronic constipation or not (10.6 and 9.9 g/day) also had lower intake of total
      fiber than the control group (13.4 g/day) (P=0.008). The intake of fiber was
      lower than the minimum recommended value (age+5 g) and statistically associated
      (P=0.021) with the recurrent abdominal pain group (78%) in comparison with the
      control one (51.2%). The odds ratio was 3.39 (95% CI, 1.18-9.95). CONCLUSION:
      fiber intake below the minimum recommended value is a risk factor for recurrent
      abdominal pain in children.

PMID- 16452918
TI  - Fat-soluble vitamins in breast-fed preterm and term infants.
AB  - OBJECTIVE: To examine the supply and status of fat-soluble vitamins in very low
      birth weight (VLBW) infants compared to a reference group of normal birth weight
      (NBW) infants. DESIGN: A longitudinal study of VLBW infants in the early neonatal
      period. Blood samples were drawn at 1 week of age and at discharge from hospital.
      Plasma was analyzed for the fat-soluble vitamins: retinol, 25-OH-vitamin D, alpha
      tocopherol and phylloquinone (vitamin K(1)) using high-performance liquid
      chromatography. SUBJECTS: A total of 40 VLBW infants were included in the study.
      A reference group of 33 NBW infants was randomly selected from one of our
      previous studies. RESULTS: The VLBW infants received fortified human milk, and
      daily oral vitamin supplement (Multibionta). In VLBW infants, plasma retinol
      concentrations decreased and plasma 25-OH-vitamin D increased during the study
      period. VLBW infants had significantly lower plasma retinol (0.3 vs 0.7 mu M) and
      higher plasma 25-OH-vitamin D (166 vs 25 nM) at discharge compared to NBW
      infants. Plasma phylloquinone concentration in VLBW infants was very high (53
      ng/ml) at one week of age, especially in the youngest infants (192 ng/ml), but
      decreased rapidly during the study period resulting in low/normal plasma
      concentrations (0.9 ng/ml) at discharge. CONCLUSIONS: We observed alterations in
      plasma concentration of retinol and 25-OH-vitamin D in VLBW infants in the early
      neonatal period, resulting in marked differences between VLBW at discharge and
      NBW. Further trials are needed to evaluate whether changes in vitamin
      supplementation may improve clinical outcome in VLBW infants.

PMID- 16452917
TI  - Epidemiology of undernutrition in adults in Dhaka slum households, Bangladesh.
AB  - OBJECTIVES: To identify socioeconomic, demographic and environmental factors that
      predict undernutrition in adults in a Dhaka slum population. DESIGN: A panel
      survey, conducted between 1995 and 1997. A random sample of households was
      selected. Socioeconomic, demographic and environmental variables were collected
      monthly by questionnaire and nutritional status was assessed. SETTING: Dhaka
      slums in Bangladesh. SUBJECTS: A total of 1097 adults surveyed during September
      December 1996. MAIN OUTCOME MEASURES: Body mass index (BMI) less than 18.5
      kg/m(2). RESULTS: There was a sex difference with female subjects having a
      significant odds ratio for low BMI compared with male subjects (P<0.03). There
      was no difference by age for males, but there was a difference by age for female
      subjects, with women aged 30-39 and 40-49 years having the worst BMI (P<0.04;
      P<0.04). The Beri Bahd area of residence had the worst BMI (P<0.001). Deficit
      situation as the self-reported financial situation had the worst BMI (P<0.03).
      Casual wage workers, unskilled and dependent self-employed individuals had the
      worst BMI (P<0.005; P<0.003). Not being involved in credit organizations and NGO
      credit organizations was associated with worst BMI (P<0.008; P<0.03). Those
      households that had an income of 2000-2499 Taka had the worst BMI (P<0.07).
      Households with a floor area of 5 m(2) or more per consumption unit had the best
      BMI (P<0.01). Households without electricity had the worst BMI (P<0.007).
      Households with tube well water had the worst BMI compared with those with tap
      water (P<0.001). CONCLUSIONS: Under nutrition was related to demographic,
      economic, social and environmental factors.

PMID- 16452919
TI  - The effect of chronic consumption of red wine polyphenols on vascular function in
      postmenopausal women.
AB  - OBJECTIVE: To elucidate whether the chronic consumption of dealcoholised red wine
      (DRW) (polyphenol-rich component) and/or red wine (RW) improves vascular function
      in hypercholesterolaemic postmenopausal women. DESIGN, SUBJECTS AND INTERVENTION:
      A randomised parallel-arm study. Forty-five hypercholesterolaemic postmenopausal
      women were randomised into either water, DRW or RW group for 6 weeks following a
      4 week washout. Fasting measures of central haemodynamic parameters, arterial
      wave reflection and endothelial nitric oxide were taken at 0 and 6 weeks.
      SETTING: Clinic in the School of Public Health, Curtin University. RESULTS: There
      were no significant between group differences in arterial stiffness as measured
      by augmentation index (AIx) and augmentation pressure (AP). However, a
      significant within group decrease in AIx (-9%, P=0.02) and AP (-12%, P=0.02) was
      observed following DRW consumption. No significant changes were observed in
      central haemodynamic parameters and endothelial nitric oxide levels following DRW
      and RW consumption, compared to water. CONCLUSIONS: Neither the chronic
      consumption of DRW nor RW improved markers of arterial stiffness, compared to
      control. However, the significant within group improvements in these indices
      following the consumption of DRW cannot be overlooked and warrant further
      investigation.

PMID- 16452920
TI  - Security and biology: scientists beware!

PMID- 16452921
TI  - E-mail decay rates among corresponding authors in MEDLINE. The ability to
      communicate with and request materials from authors is being eroded by the
      expiration of e-mail addresses.

PMID- 16452922
TI  - Science, an essential part of culture. Ignoring the fact that science is an
      integral part of human culture is a serious error if we want to overcome
      humanity's problems.

PMID- 16452923
TI  - More than the sum of their parts? Clustering is becoming more prevalent in the
      biosciences, despite concerns over the sustainability and economic effectiveness
      of science parks and hubs.

PMID- 16452924
TI  - Ancient DNA research goes nuclear. A new technique to extract sequence data from
      nuclear DNA may reveal exciting new insights into evolution and phylogeny.

PMID- 16452925
TI  - Loosening addiction's deadly grip. Recent research paints a picture of addiction
      as a progressive, chronic neurological disease that wreaks havoc with brain
      chemistry.

PMID- 16452926
TI  - Transcription in four dimensions: nuclear receptor-directed initiation of gene
      expression.
AB  - Regulated gene expression, achieved through the coordinated assembly of
      transcription factors, co-regulators and the basal transcription machinery on
      promoters, is an initial step in accomplishing cell specificity and homeostasis.
      Traditional models of transcriptional regulation tend to be static, although gene
      expression profiles change with time to adapt to developmental and environmental
      cues. Furthermore, biochemical and structural studies have determined that
      initiation of transcription progresses through a series of ordered events. By
      integrating time into the analysis of transcription, chromatin
      immunoprecipitation assays and live-cell imaging techniques have revealed the
      dynamic, cooperative, functionally redundant and cyclical nature of gene
      expression. In this review, we present a dynamic model of gene transcription that
      integrates data obtained by these two techniques.

PMID- 16452928
TI  - The influence of the surface migration of gold on the growth of silicon
      nanowires.
AB  - Interest in nanowires continues to grow, fuelled in part by applications in
      nanotechnology. The ability to engineer nanowire properties makes them especially
      promising in nanoelectronics. Most silicon nanowires are grown using the vapour
      liquid-solid (VLS) mechanism, in which the nanowire grows from a gold/silicon
      catalyst droplet during silicon chemical vapour deposition. Despite over 40 years
      of study, many aspects of VLS growth are not well understood. For example, in the
      conventional picture the catalyst droplet does not change during growth, and the
      nanowire sidewalls consist of clean silicon facets. Here we demonstrate that
      these assumptions are false for silicon nanowires grown on Si(111) under
      conditions where all of the experimental parameters (surface structure, gas
      cleanliness, and background contaminants) are carefully controlled. We show that
      gold diffusion during growth determines the length, shape, and sidewall
      properties of the nanowires. Gold from the catalyst droplets wets the nanowire
      sidewalls, eventually consuming the droplets and terminating VLS growth. Gold
      diffusion from the smaller droplets to the larger ones (Ostwald ripening) leads
      to nanowire diameters that change during growth. These results show that the
      silicon nanowire growth is fundamentally limited by gold diffusion: smooth,
      arbitrarily long nanowires cannot be grown without eliminating gold migration.

PMID- 16452934
TI  - Recycling the past.

PMID- 16452929
TI  - Development of the signal in sensory rhodopsin and its transfer to the cognate
      transducer.
AB  - The microbial phototaxis receptor sensory rhodopsin II (NpSRII, also named
      phoborhodopsin) mediates the photophobic response of the haloarchaeon
      Natronomonas pharaonis by modulating the swimming behaviour of the bacterium.
      After excitation by blue-green light NpSRII triggers, by means of a tightly bound
      transducer protein (NpHtrII), a signal transduction chain homologous with the two
      component system of eubacterial chemotaxis. Two molecules of NpSRII and two
      molecules of NpHtrII form a 2:2 complex in membranes as shown by electron
      paramagnetic resonance and X-ray structure analysis. Here we present X-ray
      structures of the photocycle intermediates K and late M (M2) explaining the
      evolution of the signal in the receptor after retinal isomerization and the
      transfer of the signal to the transducer in the complex. The formation of late M
      has been correlated with the formation of the signalling state. The observed
      structural rearrangements allow us to propose the following mechanism for the
      light-induced activation of the signalling complex. On excitation by light,
      retinal isomerization leads in the K state to a rearrangement of a water cluster
      that partly disconnects two helices of the receptor. In the transition to late M
      the changes in the hydrogen bond network proceed further. Thus, in late M state
      an altered tertiary structure establishes the signalling state of the receptor.
      The transducer responds to the activation of the receptor by a clockwise rotation
      of about 15 degrees of helix TM2 and a displacement of this helix by 0.9 A at the
      cytoplasmic surface.

PMID- 16452927
TI  - Mechanisms of genetic robustness in RNA viruses.
AB  - Two key features of RNA viruses are their compacted genomes and their high
      mutation rate. Accordingly, deleterious mutations are common and have an enormous
      impact on viral fitness. In their multicellular hosts, robustness can be achieved
      by genomic redundancy, including gene duplication, diploidy, alternative
      metabolic pathways and biochemical buffering mechanisms. However, here we review
      evidence suggesting that during RNA virus evolution, alternative robustness
      mechanisms may have been selected. After briefly describing how genetic
      robustness can be quantified, we discuss mechanisms of intrinsic robustness
      arising as consequences of RNA-genome architecture, replication peculiarities and
      quasi-species population dynamics. These intrinsic robustness mechanisms operate
      efficiently at the population level, despite the mutational sensitivity shown by
      individual genomes. Finally, we discuss the possibility that viruses might
      exploit cellular buffering mechanisms for their own benefit, producing a sort of
      extrinsic robustness.

PMID- 16452935
TI  - When a vaccine is safe.

PMID- 16452936
TI  - Malaria quagmire.

PMID- 16452938
TI  - Doubts over biochemist's data expose holes in Japanese fraud laws.

PMID- 16452939
TI  - Germany urges NASA to save airborne telescope.

PMID- 16452940
TI  - Snapshot: weather watch.

PMID- 16452941
TI  - Experts plan to reclaim the web for pop science.

PMID- 16452943
TI  - Senators seek cash to save US science.

PMID- 16452944
TI  - Stem-cell tagging shows flaws.

PMID- 16452945
TI  - Forensic software traces tweaks to images.

PMID- 16452946
TI  - Should journals police scientific fraud?

PMID- 16452950
TI  - Radio astronomy: high and dry.

PMID- 16452949
TI  - Lyme disease: uphill struggle.

PMID- 16452951
TI  - Endangered species: time to raise the devil.

PMID- 16452953
TI  - Ticking the right boxes.

PMID- 16452954
TI  - Reader-appeal should not outweigh merit of research.

PMID- 16452955
TI  - Mudskippers undermine ID claims on macroevolution.

PMID- 16452956
TI  - Conferences that welcome spouses aid research too.

PMID- 16452957
TI  - Gene-function wiki would let biologists pool worldwide resources.

PMID- 16452962
TI  - The third Bond.

PMID- 16452963
TI  - Solar system: a planet more, a planet less?

PMID- 16452964
TI  - Molecular biology: prime-time progress.

PMID- 16452966
TI  - Materials Science: colloids get complex.

PMID- 16452968
TI  - Fluid dynamics: flows like smoke and honey.

PMID- 16452967
TI  - Neurobiology: memories of a fruitfly.

PMID- 16452969
TI  - Chemistry: catalysts live and up close.

PMID- 16452970
TI  - Allograft theory: transmission of devil facial-tumour disease.
AB  - The Tasmanian devil, a large carnivorous Australian marsupial, is under threat
      from a widespread fatal disease in which a malignant oral-facial tumour obstructs
      the animal's ability to feed. Here we show that the chromosomes in these tumours
      have undergone a complex rearrangement that is identical for every animal
      studied. In light of this remarkable finding and of the known fighting behaviour
      of the devils, we propose that the disease is transmitted by allograft, whereby
      an infectious cell line is passed directly between the animals through bites they
      inflict on one another.

PMID- 16452971
TI  - Distinct memory traces for two visual features in the Drosophila brain.
AB  - The fly Drosophila melanogaster can discriminate and remember visual landmarks.
      It analyses selected parts of its visual environment according to a small number
      of pattern parameters such as size, colour or contour orientation, and stores
      particular parameter values. Like humans, flies recognize patterns independently
      of the retinal position during acquisition of the pattern (translation
      invariance). Here we show that the central-most part of the fly brain, the fan
      shaped body, contains parts of a network mediating visual pattern recognition. We
      have identified short-term memory traces of two pattern parameters--elevation in
      the panorama and contour orientation. These can be localized to two groups of
      neurons extending branches as parallel, horizontal strata in the fan-shaped body.
      The central location of this memory store is well suited to mediate translational
      invariance.

PMID- 16452972
TI  - Replication fork reactivation downstream of a blocked nascent leading strand.
AB  - Unrepaired lesions in the DNA template pose a threat to accurate replication.
      Several pathways exist in Escherichia coli to reactivate a blocked replication
      fork. The process of recombination-dependent restart of broken forks is well
      understood, but the consequence of replication through strand-specific lesions is
      less well known. Here we show that replication can be restarted and leading
      strand synthesis re-initiated downstream of an unrepaired block to leading-strand
      progression, even when the 3'-OH of the nascent leading strand is unavailable. We
      demonstrate that the loading by a replication restart system of a single hexamer
      of the replication fork helicase, DnaB, on the lagging-strand template is
      sufficient to coordinate priming by the DnaG primase of both the leading and
      lagging strands. These observations provide a mechanism for damage bypass during
      fork reactivation, demonstrate how daughter-strand gaps are generated opposite
      leading-strand lesions during the replication of ultraviolet-light-irradiated
      DNA, and help to explain the remarkable speed at which even a heavily damaged DNA
      template is replicated.

PMID- 16452973
TI  - The trans-neptunian object UB313 is larger than Pluto.
AB  - The most distant known object in the Solar System, 2003 UB313 (97 au from the
      Sun), was recently discovered near its aphelion. Its high eccentricity and
      inclination to the ecliptic plane, along with its perihelion near the orbit of
      Neptune, identify it as a member of the 'scattered disk'. This disk of bodies
      probably originates in the Kuiper belt objects, which orbit near the ecliptic
      plane in circular orbits between 30 and 50 au, and may include Pluto as a member.
      The optical brightness of 2003 UB313, if adjusted to Pluto's distance, is greater
      than that of Pluto, which suggested that it might be larger than Pluto. The
      actual size, however, could not be determined from the optical measurements
      because the surface reflectivity (albedo) was unknown. Here we report
      observations of the thermal emission of 2003 UB313 at a wavelength of 1.2 mm,
      which in combination with the measured optical brightness leads to a diameter of
      3,000 +/- 300 +/- 100 km. Here the first error reflects measurement
      uncertainties, while the second derives from the unknown object orientation. This
      makes 2003 UB313 the largest known trans-neptunian object, even larger than Pluto
      (2,300 km). The albedo is 0.60 +/- 0.10 +/- 0.05, which is strikingly similar to
      that of Pluto, suggesting that the methane seen in the optical spectrum causes a
      highly reflective icy surface.

PMID- 16452974
TI  - A low density of 0.8 g cm(-3) for the Trojan binary asteroid 617 Patroclus.
AB  - The Trojan population consists of two swarms of asteroids following the same
      orbit as Jupiter and located at the L4 and L5 stable Lagrange points of the
      Jupiter-Sun system (leading and following Jupiter by 60 degrees ). The asteroid
      617 Patroclus is the only known binary Trojan. The orbit of this double system
      was hitherto unknown. Here we report that the components, separated by 680 km,
      move around the system's centre of mass, describing a roughly circular orbit.
      Using this orbital information, combined with thermal measurements to estimate
      the size of the components, we derive a very low density of 0.8(- 0.1)+0.2 g cm(
      3). The components of 617 Patroclus are therefore very porous or composed mostly
      of water ice, suggesting that they could have been formed in the outer part of
      the Solar System.

PMID- 16452975
TI  - Disruption of extended defects in solid oxide fuel cell anodes for methane
      oxidation.
AB  - Point defects largely govern the electrochemical properties of oxides: at low
      defect concentrations, conductivity increases with concentration; however, at
      higher concentrations, defect-defect interactions start to dominate. Thus, in
      searching for electrochemically active materials for fuel cell anodes, high
      defect concentration is generally avoided. Here we describe an oxide anode formed
      from lanthanum-substituted strontium titanate (La-SrTiO3) in which we control the
      oxygen stoichiometry in order to break down the extended defect intergrowth
      regions and create phases with considerable disordered oxygen defects. We
      substitute Ti in these phases with Ga and Mn to induce redox activity and allow
      more flexible coordination. The material demonstrates impressive fuel cell
      performance using wet hydrogen at 950 degrees C. It is also important for fuel
      cell technology to achieve efficient electrode operation with different
      hydrocarbon fuels, although such fuels are more demanding than pure hydrogen. The
      best anode materials to date--Ni-YSZ (yttria-stabilized zirconia) cermets--suffer
      some disadvantages related to low tolerance to sulphur, carbon build-up when
      using hydrocarbon fuels (though device modifications and lower temperature
      operation can avoid this) and volume instability on redox cycling. Our anode
      material is very active for methane oxidation at high temperatures, with open
      circuit voltages in excess of 1.2 V. The materials design concept that we use
      here could lead to devices that enable more-efficient energy extraction from
      fossil fuels and carbon-neutral fuels.

PMID- 16452976
TI  - Spatially resolved observation of crystal-face-dependent catalysis by single
      turnover counting.
AB  - Catalytic processes on surfaces have long been studied by probing model reactions
      on single-crystal metal surfaces under high vacuum conditions. Yet the vast
      majority of industrial heterogeneous catalysis occurs at ambient or elevated
      pressures using complex materials with crystal faces, edges and defects differing
      in their catalytic activity. Clearly, if new or improved catalysts are to be
      rationally designed, we require quantitative correlations between surface
      features and catalytic activity--ideally obtained under realistic reaction
      conditions. Transmission electron microscopy and scanning tunnelling microscopy
      have allowed in situ characterization of catalyst surfaces with atomic
      resolution, but are limited by the need for low-pressure conditions and
      conductive surfaces, respectively. Sum frequency generation spectroscopy can
      identify vibrations of adsorbed reactants and products in both gaseous and
      condensed phases, but so far lacks sensitivity down to the single molecule level.
      Here we adapt real-time monitoring of the chemical transformation of individual
      organic molecules by fluorescence microscopy to monitor reactions catalysed by
      crystals of a layered double hydroxide immersed in reagent solution. By using a
      wide field microscope, we are able to map the spatial distribution of catalytic
      activity over the entire crystal by counting single turnover events. We find that
      ester hydrolysis proceeds on the lateral {1010} crystal faces, while
      transesterification occurs on the entire outer crystal surface. Because the
      method operates at ambient temperature and pressure and in a condensed phase, it
      can be applied to the growing number of liquid-phase industrial organic
      transformations to localize catalytic activity on and in inorganic solids. An
      exciting opportunity is the use of probe molecules with different size and
      functionality, which should provide insight into shape-selective or structure
      sensitive catalysis and thus help with the rational design of new or more
      productive heterogeneous catalysts.

PMID- 16452977
TI  - Malaria early warnings based on seasonal climate forecasts from multi-model
      ensembles.
AB  - The control of epidemic malaria is a priority for the international health
      community and specific targets for the early detection and effective control of
      epidemics have been agreed. Interannual climate variability is an important
      determinant of epidemics in parts of Africa where climate drives both mosquito
      vector dynamics and parasite development rates. Hence, skilful seasonal climate
      forecasts may provide early warning of changes of risk in epidemic-prone regions.
      Here we discuss the development of a system to forecast probabilities of
      anomalously high and low malaria incidence with dynamically based, seasonal
      timescale, multi-model ensemble predictions of climate, using leading global
      coupled ocean-atmosphere climate models developed in Europe. This forecast system
      is successfully applied to the prediction of malaria risk in Botswana, where
      links between malaria and climate variability are well established, adding up to
      four months lead time over malaria warnings issued with observed precipitation
      and having a comparably high level of probabilistic prediction skill. In years in
      which the forecast probability distribution is different from that of
      climatology, malaria decision-makers can use this information for improved
      resource allocation.

PMID- 16452978
TI  - Episodic growth of the Gondwana supercontinent from hafnium and oxygen isotopes
      in zircon.
AB  - It is thought that continental crust existed as early as 150 million years after
      planetary accretion, but assessing the rates and processes of subsequent crustal
      growth requires linking the apparently contradictory information from the igneous
      and sedimentary rock records. For example, the striking global peaks in juvenile
      igneous activity 2.7, 1.9 and 1.2 Gyr ago imply rapid crustal generation in
      response to the emplacement of mantle 'super-plumes', rather than by the
      continuous process of subduction. Yet uncertainties persist over whether these
      age peaks are artefacts of selective preservation, and over how to reconcile
      episodic crust formation with the smooth crustal evolution curves inferred from
      neodymium isotope variations of sedimentary rocks. Detrital zircons encapsulate a
      more representative record of igneous events than the exposed geology and their
      hafnium isotope ratios reflect the time since the source of the parental magmas
      separated from the mantle. These 'model' ages are only meaningful if the host
      magma lacked a mixed or sedimentary source component, but the latter can be
      diagnosed by oxygen isotopes, which are strongly fractionated by rock-hydrosphere
      interactions. Here we report the first study that integrates hafnium and oxygen
      isotopes, all measured in situ on the same, precisely dated detrital zircon
      grains. The data reveal that crust generation in part of Gondwana was limited to
      major pulses at 1.9 and 3.3 Gyr ago, and that the zircons crystallized during
      repeated reworking of crust formed at these times. The implication is that the
      mechanisms of crust formation differed from those of crustal differentiation in
      ancient orogenic belts.

PMID- 16452979
TI  - Functional genomics reveals genes involved in protein secretion and Golgi
      organization.
AB  - Yeast genetics and in vitro biochemical analysis have identified numerous genes
      involved in protein secretion. As compared with yeast, however, the metazoan
      secretory pathway is more complex and many mechanisms that regulate organization
      of the Golgi apparatus remain poorly characterized. We performed a genome-wide
      RNA-mediated interference screen in a Drosophila cell line to identify genes
      required for constitutive protein secretion. We then classified the genes on the
      basis of the effect of their depletion on organization of the Golgi membranes.
      Here we show that depletion of class A genes redistributes Golgi membranes into
      the endoplasmic reticulum, depletion of class B genes leads to Golgi
      fragmentation, depletion of class C genes leads to aggregation of Golgi
      membranes, and depletion of class D genes causes no obvious change. Of the 20 new
      gene products characterized so far, several localize to the Golgi membranes and
      the endoplasmic reticulum.

PMID- 16452980
TI  - Gene network shaping of inherent noise spectra.
AB  - Recent work demonstrates that stochastic fluctuations in molecular populations
      have consequences for gene regulation. Previous experiments focused on noise
      sources or noise propagation through gene networks by measuring noise magnitudes.
      However, in theoretical analysis, we showed that noise frequency content is
      determined by the underlying gene circuits, leading to a mapping between gene
      circuit structure and the noise frequency range. An intriguing prediction from
      our previous studies was that negative autoregulation shifts noise to higher
      frequencies where it is more easily filtered out by gene networks--a property
      that may contribute to the prevalence of autoregulation motifs (for example,
      found in the regulation of approximately 40% of Escherichia coli genes). Here we
      measure noise frequency content in growing cultures of E. coli, and verify the
      link between gene circuit structure and noise spectra by demonstrating the
      negative autoregulation-mediated spectral shift. We further demonstrate that
      noise spectral measurements provide mechanistic insights into gene regulation, as
      perturbations of gene circuit parameters are discernible in the measured noise
      frequency ranges. These results suggest that noise spectral measurements could
      facilitate the discovery of novel regulatory relationships.

PMID- 16452981
TI  - Structure of epsilon15 bacteriophage reveals genome organization and DNA
      packaging/injection apparatus.
AB  - The critical viral components for packaging DNA, recognizing and binding to host
      cells, and injecting the condensed DNA into the host are organized at a single
      vertex of many icosahedral viruses. These component structures do not share
      icosahedral symmetry and cannot be resolved using a conventional icosahedral
      averaging method. Here we report the structure of the entire infectious
      Salmonella bacteriophage epsilon15 (ref. 1) determined from single-particle cryo
      electron microscopy, without icosahedral averaging. This structure displays not
      only the icosahedral shell of 60 hexamers and 11 pentamers, but also the non
      icosahedral components at one pentameric vertex. The densities at this vertex can
      be identified as the 12-subunit portal complex sandwiched between an internal
      cylindrical core and an external tail hub connecting to six projecting trimeric
      tailspikes. The viral genome is packed as coaxial coils in at least three outer
      layers with approximately 90 terminal nucleotides extending through the protein
      core and the portal complex and poised for injection. The shell protein from
      icosahedral reconstruction at higher resolution exhibits a similar fold to that
      of other double-stranded DNA viruses including herpesvirus, suggesting a common
      ancestor among these diverse viruses. The image reconstruction approach should be
      applicable to studying other biological nanomachines with components of mixed
      symmetries.

PMID- 16452982
TI  - The mechanism of DNA replication primer synthesis by RNA polymerase.
AB  - RNA primers for DNA replication are usually synthesized by specialized enzymes,
      the primases. However, some replication systems have evolved to use cellular DNA
      dependent RNA polymerase for primer synthesis. The main requirement for the
      replication primer, an exposed RNA 3' end annealed to the DNA template, is not
      compatible with known conformations of the transcription elongation complex,
      raising a question of how the priming is achieved. Here we show that a previously
      unrecognized kind of transcription complex is formed during RNA polymerase
      catalysed synthesis of the M13 bacteriophage replication primer. The complex
      contains an overextended RNA-DNA hybrid bound in the RNA-polymerase trough that
      is normally occupied by downstream double-stranded DNA, thus leaving the 3' end
      of the RNA available for interaction with DNA polymerase. Transcription complexes
      with similar topology may prime the replication of other bacterial mobile
      elements and may regulate transcription elongation under conditions that favour
      the formation of an extended RNA-DNA hybrid.

PMID- 16452983
TI  - DNA primase acts as a molecular brake in DNA replication.
AB  - A hallmark feature of DNA replication is the coordination between the continuous
      polymerization of nucleotides on the leading strand and the discontinuous
      synthesis of DNA on the lagging strand. This synchronization requires a precisely
      timed series of enzymatic steps that control the synthesis of an RNA primer, the
      recycling of the lagging-strand DNA polymerase, and the production of an Okazaki
      fragment. Primases synthesize RNA primers at a rate that is orders of magnitude
      lower than the rate of DNA synthesis by the DNA polymerases at the fork.
      Furthermore, the recycling of the lagging-strand DNA polymerase from a finished
      Okazaki fragment to a new primer is inherently slower than the rate of nucleotide
      polymerization. Different models have been put forward to explain how these slow
      enzymatic steps can take place at the lagging strand without losing coordination
      with the continuous and fast leading-strand synthesis. Nonetheless, a clear
      picture remains elusive. Here we use single-molecule techniques to study the
      kinetics of a multiprotein replication complex from bacteriophage T7 and to
      characterize the effect of primase activity on fork progression. We observe the
      synthesis of primers on the lagging strand to cause transient pausing of the
      highly processive leading-strand synthesis. In the presence of both leading- and
      lagging-strand synthesis, we observe the formation and release of a replication
      loop on the lagging strand. Before loop formation, the primase acts as a
      molecular brake and transiently halts progression of the replication fork. This
      observation suggests a mechanism that prevents leading-strand synthesis from
      outpacing lagging-strand synthesis during the slow enzymatic steps on the lagging
      strand.

PMID- 16452984
TI  - Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto
      inhibited state.
AB  - Epac proteins (exchange proteins directly activated by cAMP) are guanine
      nucleotide-exchange factors (GEFs) for the small GTP-binding proteins Rap1 and
      Rap2 that are directly regulated by the second messenger cyclic AMP and function
      in the control of diverse cellular processes, including cell adhesion and insulin
      secretion. Here we report the three-dimensional structure of full-length Epac2, a
      110-kDa protein that contains an amino-terminal regulatory region with two cyclic
      nucleotide-binding domains and a carboxy-terminal catalytic region. The structure
      was solved in the absence of cAMP and shows the auto-inhibited state of Epac. The
      regulatory region is positioned with respect to the catalytic region by a rigid,
      tripartite beta-sheet-like structure we refer to as the 'switchboard' and an
      ionic interaction we call the 'ionic latch'. As a consequence of this
      arrangement, the access of Rap to the catalytic site is sterically blocked.
      Mutational analysis suggests a model for cAMP-induced Epac activation with rigid
      body movement of the regulatory region, the features of which are universally
      conserved in cAMP-regulated proteins.

PMID- 16452986
TI  - Antidepressant-like effects of the corticotropin-releasing factor 1 receptor
      antagonist, SSR125543, and the vasopressin 1b receptor antagonist, SSR149415, in
      a DRL-72 s schedule in the rat.
AB  - The vasopressin 1b receptor antagonist, SSR149415, and the corticotropin
      releasing factor 1 receptor antagonist, SSR125543, are orally active non-peptidic
      compounds with anxiolytic- and antidepressant-like activities in animal models.
      Presently, SSR149415 and SSR125543 were evaluated in a differential reinforcement
      of low-rate 72 s (DRL-72 s) schedule, a procedure known to respond differentially
      to antidepressants and anxiolytics. Male Wistar rats were trained to lever-press
      for food reinforcement, but only lever-presses occurring after a 72 s delay were
      reinforced; otherwise, presses were not rewarded, and the timer was reset to 0 s.
      The selective serotonin reuptake inhibitor, fluoxetine, and the benzodiazepine
      anxiolytic, diazepam, were tested in parallel. SSR149415 (10-30 mg/kg, i.p.) and
      SSR125543 (30 mg/kg, i.p.) increased the percentage of responses emitted in the
      inter-response time (IRT) bin (49-96 s), which resulted in a greater number of
      reinforced presses. Both compounds shifted the frequency distribution of
      responses toward longer IRT durations, with a preservation of the bell shape of
      the IRT distribution curve. Fluoxetine (10 mg/kg, i.p.) had an effect on DRL-72 s
      similar to that of SSR149415 and SSR125543. By contrast, diazepam increased the
      number of responses in IRT bin (0-12 s), and the IRT distribution curve was
      shifted toward shorter IRT durations and flattened. In summary, these results
      show that SSR149415 and SSR125543 displayed antidepressant-like activity in a DRL
      72 s schedule in rat, confirming their therapeutic potential for the treatment of
      pathological states induced by chronic frustration such as depression.

PMID- 16452987
TI  - Stimulation of adenosine receptors selectively activates gene expression in
      striatal enkephalinergic neurons.
AB  - In the striatum, adenosine A2A and dopamine D2 receptors exert reciprocal
      antagonistic interactions that modulate the function of GABAergic enkephalinergic
      neurons. We have previously shown that stimulation of adenosine A1 receptors
      allows the stimulation of A2A receptors to overcome a tonic inhibitory effect of
      D2 receptors and induce striatal expression of c-fos. In the present work, by
      studying co-localization of c-Fos immunoreactivity and preproenkephalin and
      preprodynorphin transcripts, we show that co-administration of the A1 receptor
      agonist CPA and the A2A receptor agonist CGS 21680 increases the striatal
      expression of c-fos in GABAergic enkephalinergic but not in GABAergic
      dynorphinergic neurons. Co-administration of CPA and CGS 21680 also induced a
      significant increase in the striatal expression of preproenkephalin. The results
      underscore the role of adenosine in the activation of gene expression in the
      GABAergic enkephalinergic neuron.

PMID- 16452989
TI  - Loss of serotonin transporter protein after MDMA and other ring-substituted
      amphetamines.
AB  - We studied in vivo expression of the serotonin transporter (SERT) protein after
      3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine (PCA), or
      fenfluramine (FEN) treatments, and compared the effects of substituted
      amphetamines to those of 5,7-dihydroxytryptamine (5,7-DHT), an established
      serotonin (5-HT) neurotoxin. All drug treatments produced lasting reductions in 5
      HT, 5-HIAA, and [(3)H]paroxetine binding, but no significant change in the
      density of a 70 kDa band initially thought to correspond to the SERT protein.
      Additional Western blot studies, however, showed that the 70 kDa band did not
      correspond to the SERT protein, and that a diffuse band at 63-68 kDa, one that
      had the anticipated regional brain distribution of SERT protein
      (midbrain>striatum>neocortex>cerebellum), was reduced after 5,7-DHT and was
      absent in SERT-null animals, was decreased after MDMA, PCA, or FEN treatments. In
      situ immunocytochemical (ICC) studies with the same two SERT antisera used in
      Western blot studies showed loss of SERT-immunoreactive (IR) axons after 5,7-DHT
      and MDMA treatments. In the same animals, tryptophan hydroxylase (TPH)-IR axon
      density was comparably reduced, indicating that serotonergic deficits after
      substituted amphetamines differ from those in SERT-null animals, which have
      normal TPH levels but, in the absence of SERT, develop apparent neuroadaptive
      changes in 5-HT metabolism. Together, these results suggest that lasting
      serotonergic deficits after MDMA and related drugs are unlikely to represent
      neuroadaptive metabolic responses to changes in SERT trafficking, and favor the
      view that substituted amphetamines have the potential to produce a distal axotomy
      of brain 5-HT neurons.

PMID- 16452988
TI  - Upregulation of ionotropic glutamate receptor subunits within specific
      mesocorticolimbic regions during chronic nicotine self-administration.
AB  - Nicotine, an addictive substance, is the major psychoactive component in
      cigarette smoke. Both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      and N-methyl-D-aspartate (NMDA) receptors are essential for the acute stimulative
      effects of nicotine on the mesocorticolimbic dopamine system, yet little is known
      about the effects of chronic nicotine treatment on glutamate receptors.
      Therefore, we used a model of chronic nicotine self-administration (SA), which
      emulates important aspects of nicotine intake by humans, to determine whether
      glutamate receptor subunits were affected. After 18 days of saline vs nicotine
      SA, ionotropic glutamate receptor subunit levels were determined in brain regions
      within the mesocorticolimbic system by Western blotting. In prefrontal cortex
      (PFC), the levels of NMDA receptor subunit 2A (NR2A) and NR2B were increased by
      67% (p=0.04) and 83% (p=0.027), respectively. In the ventral tegmental area
      (VTA), glutamate receptor subunit 2/3 (GluR2/3) increased by 34% (p=0.011).
      Nicotine SA did not affect the expression of these subunits in dorsal striatum
      and nucleus accumbens. These findings suggest that chronic nicotine SA
      selectively increased the levels of ionotropic glutamate receptor subunits in a
      brain region-specific manner.

PMID- 16452990
TI  - A null mutation of the serotonin 6 receptor alters acute responses to ethanol.
AB  - The anatomical distribution and pharmacology of serotonin 6 receptors (5-HT6Rs)
      implicate them as contributors to the serotonergic regulation of complex
      behavior. To complement the limited range of pharmacological tools available to
      examine 5-HT6R function, we have generated a mouse line bearing a constitutive
      null mutation of the 5-HT6R gene. No perturbations of baseline behavior were
      noted in a wide array of assays pertinent to multiple neurobehavioral processes.
      However, 5-HT6R mutant mice demonstrated reduced responses to the ataxic and
      sedative effects of ethanol. No differences in ethanol metabolism were evident
      between wild-type and 5-HT6R mutant mice. These findings implicate 5-HT6Rs in the
      serotonergic modulation of responses to ethanol.

PMID- 16452991
TI  - The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha
      activate serotonin transporters.
AB  - Proinflammatory cytokines and serotonergic homeostasis have both been implicated
      in the pathophysiology of major psychiatric disorders. We have demonstrated that
      activation of p38 mitogen-activated protein kinase (MAPK) induces a catalytic
      activation of the serotonin transporter (SERT) arising from a reduction in the
      SERT Km for 5-hydroxytryptamine (5-HT). As inflammatory cytokines can activate
      p38 MAPK, we hypothesized that they might also activate neuronal SERT. Indeed,
      Interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha)
      stimulated serotonin uptake in both the rat embryonic raphe cell line, RN46A, and
      in mouse midbrain and striatal synaptosomes. In RN46A cells, IL-1beta stimulated
      5-HT uptake in a dose- and time-dependent manner, peaking in 20 min at 100 ng/ml.
      This was abolished by IL-1ra (20 ng/ml), an antagonist of the IL-1 receptor, and
      by SB203580 (5 microM), a p38 MAPK inhibitor. TNF-alpha also dose- and time
      dependently stimulated 5-HT uptake that was only partially blocked by SB203580.
      Western blots showed that IL-1beta and TNF-alpha activated p38 MAPK, in an
      SB203580-sensitive manner. IL-1beta induced an SB203580-sensitive decrease in 5
      HT Km with no significant change in Vmax. In contrast, TNF-alpha stimulation
      decreased 5-HT Km and increased SERT Vmax. SB203580 selectively blocked the TNF
      alpha-induced change in SERT Km. In mouse midbrain and striatal synaptosomes,
      maximal stimulatory effects on 5-HT uptake occurred at lower concentrations (IL
      1beta, 10 ng/ml; TNF-alpha, 20 ng/ml), and over shorter incubation times (10
      min). As with RN46A cells, the effects of IL-1beta and TNF-alpha were completely
      (IL-1beta) or partially (TNF-alpha) blocked by SB203580. These results provide
      the first evidence that proinflammatory cytokines can acutely regulate neuronal
      SERT activity via p38 MAPK-linked pathways.

PMID- 16452992
TI  - Blockade of 5-HT1A receptors by (+/-)-pindolol potentiates cortical 5-HT outflow,
      but not antidepressant-like activity of paroxetine: microdialysis and behavioral
      approaches in 5-HT1A receptor knockout mice.
AB  - Selective serotonin reuptake inhibitors like paroxetine (Prx) often requires 4-6
      weeks to achieve clinical benefits in depressed patients. Pindolol shortens this
      delay and it has been suggested that this effect is mediated by somatodendritic 5
      hydroxytryptamine (5-HT) 1A autoreceptors. However clinical data on the
      beneficial effects of pindolol are conflicting. To study the effects of (+/-)
      pindolol-paroxetine administration, we used genetical and pharmacological
      approaches in 5-HT1A knockout mice (5-HT1A-/-). Two assays, in vivo intracerebral
      microdialysis in awake mice and the forced swimming test (FST), were used to
      assess the antidepressant-like effects of this drug combination. Basal levels of
      extracellular serotonin, 5-HT ([5-HT]ext) in the frontal cortex (FCX) and the
      dorsal raphe nucleus (DRN) did not differ between the two strains of mice,
      suggesting a lack of tonic control of 5-HT1A autoreceptors on nerve terminal 5-HT
      release. Prx (1 and 4 mg/kg) dose-dependently increased cortical [5-HT]ext in
      both genotypes, but the effects were greater in mutants. The selective 5-HT1A
      receptor antagonist, WAY-100635 (0.5 mg/kg), or (+/-)-pindolol (5 and 10 mg/kg)
      potentiated the effects of Prx (4 mg/kg) on cortical [5-HT]ext in 5-HT1A+/+, but
      not in 5-HT1A-/- mice. Similar responses were obtained following local intra
      raphe perfusion by reverse microdialysis of either WAY-100635 or (+/-)-pindolol
      (100 microM each). In the FST, Prx administration dose-dependently decreased the
      immobility time in both strains of mice, but the response was much greater in
      5HT1A-/- mice. In contrast, (+/-)-pindolol blocked Prx-induced decreases in the
      immobility time while WAY-100635 had no effect in both genotypes. These findings
      using 5-HT1A-/- mice confirm that (+/-)-pindolol behaves as an antagonist of 5
      HT1A autoreceptor in mice, but its blockade of paroxetine-induced antidepressant
      like effects in the FST may be due to its binding to other neurotransmitter
      receptors.

PMID- 16452993
TI  - Unlimited access to heroin self-administration: independent motivational markers
      of opiate dependence.
AB  - The goal of the present study was to develop and validate an animal model of
      unlimited access to intravenous heroin self-administration combined with
      responding for food and water to characterize the transition to drug dependence.
      Male Wistar rats were allowed to lever press for heroin (60 microg/kg/0.1 ml
      infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in
      consecutive, daily 23-h sessions. Daily heroin intake increased over days,
      reaching significance by Day 14. Drug-taking increased across the circadian
      cycle, reflected as increases in both the nocturnal peak and diurnal nadir of
      heroin intake. Changes in the circadian pattern of food intake and meal
      patterning preceded and paralleled the changes in heroin intake. By Day 7, the
      circadian amplitude of feeding was blunted. Nocturnal intake decreased because
      rats consumed smaller and briefer meals. Diurnal intake increased due to
      increased meal frequency, whereas total daily food intake decreased. To control
      for time or experience in the self-administration boxes as a possible confound,
      rats with saline (no drug) tethers were tested and did not display significant
      changes in food intake pattern. Body weight gain slowed slightly in heroin rats
      relative to saline controls. Separate groups of rats revealed that significant
      physical dependence as measured by physical signs of opiate withdrawal following
      a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14.
      Significant increases in heroin intake could be produced using low doses of
      naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks
      of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04,
      and 0.2 mg/kg, s.c.) showed a dose-dependent reduction in heroin intake. Changes
      in the pattern of drug and food intake in the present unlimited heroin access
      model may serve as independent motivational markers for the transition to a drug
      dependent state.

PMID- 16452994
TI  - Endothelial progenitor cells in the vascular pathophysiology of hypertension:
      arterial stiffness, ageing and more.

PMID- 16452995
TI  - Initial combination therapy with olmesartan/hydrochlorothiazide in moderate-to
      severe hypertension.

PMID- 16452996
TI  - Evidence for renoprotection by blockade of the renin-angiotensin-aldosterone
      system in hypertension and diabetes.
AB  - The incidence of end-stage renal disease (ESRD) is rising worldwide, accompanied
      by corresponding increases in the risk of morbidity and mortality. Underlying
      this trend are increasing rates of hypertension and diabetes mellitus, the two
      most common causes of ESRD. In addition to the adverse haemodynamic effects of
      hypertension on the kidney, elevated blood pressure (BP) can activate components
      of the renin-angiotensin-aldosterone system (RAAS), which, in turn, activate
      mediators of inflammation, oxidative stress, cell growth, and matrix
      accumulation. Lowering BP reduces the risk of cardiovascular events and renal
      damage. Accumulating evidence from clinical and laboratory studies suggests that
      interrupting the RAAS with therapies such as angiotensin-converting enzyme
      inhibitors, angiotensin II receptor blockers, and aldosterone receptor blockers
      can interfere with the mechanisms that promote diabetic and non-diabetic renal
      damage. Moreover, clinical trials of RAAS blockade have demonstrated reductions
      in microalbuminuria, a predictor of increased cardiorenal risk and overt
      nephropathy in patients with and without diabetes and/or hypertension. In this
      way, agents that block the RAAS should be considered the drugs of first choice as
      they provide enhanced renoprotection compared with other classes of
      antihypertensive agents such as calcium channel blockers and beta-blockers.

PMID- 16452997
TI  - Do motorcyclists have erectile dysfunction? A preliminary study.
AB  - The aim of the present study was to evaluate the relationship between
      motorcycling and erectile dysfunction (ED). We investigated the relationship
      between motorcycling and erectile function using the 5-items version of the
      International Index of Erectile Function (IIEF5) in 234 motorcyclists (response
      rate 75%) and 752 healthy controls (response rate 66%). In all, 161 (69%) of 234
      motorcyclists were diagnosed as ED based on IIEF5. The prevalence of ED in the
      motorcycle group increased by age as: 58, 63, 76 and 93%, for motorcyclists in 20
      29, 30-39, 40-49 and 50-59 years, respectively. There was a significant
      difference in the prevalence of ED between the motorcycle group and the control
      group in all age groups. On stepwise logistic regression analysis, motorcycling
      was the strongest risk factor for ED. Although the severity of ED in
      motorcyclists was not so severe, motorcycling may be one of risk factors for ED.

PMID- 16452998
TI  - Genetic architecture of tuberculosis resistance in a mouse model of infection.
AB  - Tuberculosis remains a significant public health problem: one-third of the human
      population is infected with virulent Mycobacterium tuberculosis (MTB) and 10% of
      those are at risk of developing tuberculosis during their lifetime. In both
      humans and experimental animal models, genetic variation among infected
      individuals contributes to the outcome of infection. However, in immunocompetent
      individuals (the majority of patients), genetic determinants of susceptibility to
      tuberculosis remain largely unknown. Mouse models of MTB infection, allowing
      control of exposure and other potential environmental contributors, have proven
      extremely useful for examining this genetic component. In a cross of C3HeB/FeJ
      (susceptible) by C57BL/6J (resistant) inbred mouse strains, we have previously
      identified one major genetic locus, sst1, the susceptible allele of which did not
      confer an overt immunodeficiency, but rather specifically affected progression of
      lung tuberculosis. Having generated and tested the sst1 congenic strains, we have
      observed that this locus only partially explained the difference in
      susceptibility of the parental strains to MTB. We now present further studies
      controlling for the effect of the sst1, identify four additional tuberculosis
      susceptibility loci and characterize their effects by testing an independent
      cross, knockout or congenic mice.

PMID- 16452999
TI  - CD38+ chronic lymphocytic leukaemia cells co-express high levels of ZAP-70 and
      are functionally distinct from their CD38- counter-parts.

PMID- 16453001
TI  - Induction of cell death in adult T-cell leukemia cells by a novel IkappaB kinase
      inhibitor.
AB  - NF-kappaB is constitutively activated in adult T-cell leukemia (ATL) and is
      considered responsible for cell growth and prevention of cell death. In this
      study, we demonstrate that NF-kappaB is constitutively activated in various HTLV
      1-infected T-cell lines and ATL-derived cell lines irrespectively of Tax
      expression as evidenced by the phosphorylation of IkappaBalpha and p65 subunit of
      NF-kappaB, activation of NF-kappaB DNA binding, and upregulation of various
      target genes including bcl-xL, bcl-2, XIAP, c-IAP1, survivin, cyclinD1, ICAM-1
      and VCAM-1. The effects of a novel IkappaB kinase (IKK) inhibitor, 2-amino-6-[2
      (cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile (ACHP),
      were examined on cell growth of these cell lines and fresh ATL leukemic cells. We
      found that ACHP could inhibit the phosphorylation of IkappaBalpha and p65, as
      well as NF-kappaB DNA-binding, associated with downregulation of the NF-kappaB
      target genes and induce cell growth arrest and apoptosis in these cells. When Tax
      active and Tax-inactive cell lines were compared, ACHP could preferentially
      inhibit cell growth of Tax-active cells. Moreover, ACHP exhibited strong
      apoptosis-inducing activity in fresh ATL cells. These findings indicate that ACHP
      and its derivatives are effective in inducing ATL cell death and thus feasible
      candidates for the treatment of ATL.

PMID- 16453000
TI  - Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors:
      evidence for horizontal transfer of mRNA and protein delivery.
AB  - Membrane-derived vesicles (MV) are released from the surface of activated
      eucaryotic cells and exert pleiotropic effects on surrounding cells. Since the
      maintenance of pluripotency and undifferentiated propagation of embryonic stem
      (ES) cells in vitro requires tight cell to cell contacts and effective
      intercellular signaling, we hypothesize that MV derived from ES cells (ES-MV)
      express stem cell-specific molecules that may also support self-renewal and
      expansion of adult stem cells. To address this hypothesis, we employed expansion
      of hematopoietic progenitor cells (HPC) as a model. We found that ES-MV (10
      microg/ml) isolated from murine ES cells (ES-D3) in serum-free cultures
      significantly (i) enhanced survival and improved expansion of murine HPC, (ii)
      upregulated the expression of early pluripotent (Oct-4, Nanog and Rex-1) and
      early hematopoietic stem cells (Scl, HoxB4 and GATA 2) markers in these cells,
      and (iii) induced phosphorylation of MAPK p42/44 and serine-threonine kinase AKT.
      Furthermore, molecular analysis revealed that ES-MV express Wnt-3 protein and are
      selectively highly enriched in mRNA for several pluripotent transcription factors
      as compared to parental ES cells. More important, this mRNA could be delivered by
      ES-MV to target cells and translated into the corresponding proteins. The
      biological effects of ES-MV were inhibited after heat inactivation or
      pretreatment with RNAse, indicating a major involvement of protein and mRNA
      components of ES-MV in the observed phenomena. We postulate that ES-MV may
      efficiently expand HPC by stimulating them with ES-MV expressed ligands (e.g.,
      Wnt-3) as well as increase their pluripotency after horizontal transfer of ES
      derived mRNA.

PMID- 16453002
TI  - Bax gene G(-248)A promoter polymorphism and chronic lymphocytic leukemia: lack of
      association with incidence, disease stage and progression-free survival.

PMID- 16453003
TI  - AML patients with CEBPalpha mutations mostly retain identical mutant patterns but
      frequently change in allelic distribution at relapse: a comparative analysis on
      paired diagnosis and relapse samples.
AB  - The roles of CEBPalpha mutations and its cooperating mutations in the relapse of
      acute myeloid leukemia (AML) are not clear. CEBPalpha mutations were analyzed on
      149 patients with de novo AML at both diagnosis and relapse. Twenty-two patients
      (14.8%) had the mutations at diagnosis, two patients had N-terminal nonsense
      mutations alone, one had homozygous inframe duplication at the bZIP domain, and
      19 patients had both N-terminal and bZIP mutations. Twenty patients relapsed with
      identical mutant patterns, two lost CEBPalpha mutations and none acquired the
      mutations at relapse. Cloning analysis showed that the N-terminal and C-terminal
      mutations occurred on separate cloned alleles and also on the same alleles in
      most of the diagnosis and relapse samples. Losing one of the two or more
      mutations on the same allele or acquiring the other mutation on the allele
      original carrying single mutation were observed not infrequently in the paired
      samples analyzed. Seven patients with CEBPalpha mutations had cooperating
      mutations with FLT3/ITD, FLT3/TKD or N-ras but not K-ras mutations. Our study
      showed that 91% of de novo AML harboring CEBPalpha mutations at diagnosis
      retained the identical mutant patterns but frequently changed in the allelic
      distribution at relapse.

PMID- 16453004
TI  - JAK2 V617F mutation, PRV-1 overexpression and endogenous erythroid colony
      formation show different coexpression patterns among Ph-negative chronic
      myeloproliferative disorders.

PMID- 16453005
TI  - Cytogenetic response to prior treatment with interferon-alpha is predictive for
      survival after allogeneic hematopoietic stem cell transplantation in chronic
      myeloid leukemia.
AB  - We investigated the impact of a cytogenetic response (CyR) to IFN prior to and at
      the time of allogeneic hematopoietic stem cell transplantation (HSCT) on
      transplant-related mortality (TRM), relapse rate and survival probability after
      HSCT in 162 transplanted patients with chronic myeloid leukemia. One-hundred-one
      patients (62.3%) achieved a CyR prior to HSCT. Survival probabilities were higher
      in patients, who achieved any CyR prior to HSCT than in patients without CyR
      (63.6 vs 49.2%: P = 0.019). Survival probabilities in patients, who achieved a
      major CyR were better than in patients with minimal and minor CyR or in patients
      with no CyR (69.4 vs 58.8% vs 49.2%: P = 0.040). TRM and survival of chronic
      phase patients without CyR at the time of HSCT were similar to that of patients
      transplanted in advanced phase. Both groups combined had an outcome inferior to
      patients with at least minimal CyR (TRM, Gray test: P = 0.016, survival, log-rank
      test: P = 0.002). Univariate and multivariate analyses identified CyR prior to or
      at HSCT as a strong and independently favorable prognostic factor. We therefore
      conclude that allogeneic HSCT in CyR should be investigated prospectively as an
      alternative treatment option in defined patient groups.

PMID- 16453006
TI  - Decoupling of normal CD40/interleukin-4 immunoglobulin heavy chain switch signal
      leads to genomic instability in SGH-MM5 and RPMI 8226 multiple myeloma cell
      lines.
AB  - The processes mediating genomic instability and clonal evolution are obscure in
      multiple myeloma (MM). Acquisition of new chromosomal translocations into the
      switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in
      MM, often heralds transformation to more aggressive disease. Since the combined
      effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch
      recombination (CSR), and this process involves DNA double strand break repair
      (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce
      abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this
      study, we show that MM cell lines that are optimally triggered via CD40 and/or IL
      4 demonstrate abnormal decoupling of IL-4 signal transduction from CD40.
      Specifically, CD40 alone was sufficient to trigger maximal growth of tumor cells.
      We further demonstrate that CD40 triggering induced both DNA DSBs as well as
      newly acquired karyotypic abnormalities in MM cell lines. Importantly, these
      observations were accompanied by induction of activation induced cytidine
      deaminase expression, but not gross apoptosis. These data support the role of
      abnormal CD40 signal transduction in mediating genomic instability, suggesting a
      role for the CD40 pathway and intermediates in myelomagenesis and clonal
      evolution in vivo.

PMID- 16453007
TI  - Early variable-flow nasal continuous positive airway pressure in infants < or
      =1000 grams at birth.
AB  - OBJECTIVE: To compare the incidence of chronic lung disease (CLD) in extremely
      low birth weight (ELBW, < or =1000 g) infants before and after the introduction
      of early, preferential application of nasal continuous airway pressure (NCPAP)
      utilizing a variable flow delivery system. STUDY DESIGN: A retrospective cohort
      study of ELBW infants 2 years prior to (Pre-early NCPAP, n=96) and 2 years
      following (Early NCPAP, n=75) the initiation of an early NCPAP policy. RESULTS:
      There were no significant changes (Pre-early NCPAP vs Early NCPAP) in the
      incidences of CLD (35 vs 33%, P=0.81) or CLD or death (50 vs 43%, P=0.34).
      Infants in the Early NCPAP group weaned off mechanical ventilation and
      supplemental oxygen more rapidly than infants in the Pre-early NCPAP group
      (hazard ratio (HR) 1.80, P=0.002 and HR 1.69, P=0.01). CONCLUSION: A policy of
      early NCPAP has not decreased the incidence of CLD despite a decrease in time to
      successful tracheal extubation.

PMID- 16453008
TI  - Effect of magnitude and timing of maternal pregnancy blood lead (Pb) levels on
      birth outcomes.
AB  - OBJECTIVE: Associations between magnitude and timing of maternal pregnancy blood
      lead (Pb) levels (BLLs), birth weight, and total days of gestation were examined,
      as well as associations with related clinical diagnoses of low birth weight
      (LBW), preterm, and small-for-gestational-age (SGA) birth. STUDY DESIGN: Among a
      sample of 262 mother-infant pairs studied retrospectively, one-way analysis of
      variance and regression statistics were used to measure the relationship between
      level of maternal pregnancy BLLs and birth outcomes while controlling for key
      maternal and newborn factors. RESULTS: Women with maximum pregnancy BLLs (max
      PBLLs) > or =10 microg/dl tended to give birth earlier and their babies were at
      substantially increased risk for preterm and SGA birth. By holding other
      explanatory factors constant, each unit increase in max-PBLL above 10 mug/dl was
      found to be associated with a decrease of -0.3 in total days of gestation.
      Compared to women with lower levels, women with max-PBLLs > or =10 microg/dl were
      at a threefold increased risk for preterm birth (adjusted OR=3.2, 95% CI 1.2-7.4)
      and more than a fourfold increased risk for having an SGA infant (adjusted
      OR=4.2, 1.3-13.9). Second trimester maximum BLLs > or =10 microg/dl were
      associated with a steep decrease in total days of gestation (a decrease of -1.0
      days per each unit increase above 10 microg/dl). CONCLUSIONS: These data provide
      evidence of the adverse effects of maternal pregnancy BLLs, particularly when
      levels are > or =10 microg/dl. Prenatal Pb exposure at these levels was
      associated with significant decreases in total days of gestation and an increased
      risk of preterm and SGA birth.

PMID- 16453010
TI  - Gene therapy progress and prospects--vectorology: design and production of
      expression cassettes in AAV vectors.
AB  - Adeno-associated virus (AAV) derived vectors are considered highly eligible
      vehicles for human gene therapy. Not only do they possess many great potential
      for clinical applications due to their wide range of tissue targets but also
      their excellent preclinical safety profile makes them particularly suitable
      candidates for treating serious diseases. Initial clinical trials have yielded
      encouraging results and prompted further improvements in their design and methods
      of production. Many studies have been performed to modify the tropism of
      recombinant (r)AAV by capsid modification. However, the precise control of
      spatial and temporal gene expression, which may be important in determining the
      safety and efficacy of gene transfer, lies in a rational choice and a subtle
      combination of various regulatory genetic elements to be inserted into the
      expression cassette. Moreover, new strategies based on such genetic sequences
      open new perspectives for enhancing vector genome persistence, disrupting or
      reducing pathogenic gene expression and even targeting genes.

PMID- 16453009
TI  - Therapeutic short hairpin RNA expression in the liver: viral targets and vectors.
AB  - Over 500 million people worldwide are infected with one or more different and
      unrelated types of human hepatitis virus. Such individuals are at a high risk of
      developing acute or chronic hepatic disease, and ultimately dying from sequelae.
      Although a vaccine is available for hepatitis A and B virus, treatment options
      for chronically infected patients are limited, and particularly ineffective in
      case of hepatitis C virus (HCV) infection. A promising new avenue currently being
      explored is to harness the power of RNA interference for development of an
      antiviral therapy. The timing to pursue this particular approach is excellent,
      with the first in vivo animal models for HCV infection becoming available, and
      the technology for liver-specific expression of short hairpin RNAs advancing at a
      rapid pace. Here, we critically review these important current developments, and
      discuss the next steps to bring this novel approach into the clinics.

PMID- 16453011
TI  - Successful in vivo tumor targeting of prostate-specific membrane antigen with a
      highly efficient J591/PEI/DNA molecular conjugate.
AB  - We have utilized a novel polyethylenimine (PEI)/DNA-betagal vector to investigate
      the specificity and efficiency of immuno-targeting prostate-specific membrane
      antigen (PSMA). Coupling of the PSMA-specific monoclonal antibody, J591, to the
      vector was facilitated via the high-affinity interaction between
      phenyl(di)boronic acid and salicylhydroxamic acid molecules. Highly efficient
      gene delivery by this prostate cancer (PCA)-targeted J591/polyethylene glycol
      (PEG)/PEI/DNA-betagal vector was demonstrated in PSMA-positive cells relative to
      controls, resulting in significant growth inhibition in vitro when the
      J591/PEG/PEI/DNA-p53 was used. Competition with free antibody resulted in about
      90% reduction in both J591 internalization and betagal gene delivery, indicating
      specificity for PSMA-positive cells. More importantly, testing the efficiency of
      the J591/PEG/PEI/DNA-betagal targeting vector in an orthotopic PCA model in nude
      mice resulted in up to a 20-fold increase in gene delivery over the untargeted
      vector controls. The in vivo organ distribution profile also revealed betagal
      expression predominantly in the tumor, which was more than 1 log higher than the
      next highest level of expression in the lung. Furthermore, with the targeted
      vector containing the gene for yellow fluorescent protein or biotinylated J591,
      we further demonstrate in vivo that vector-mediated gene delivery is specific for
      both tumor cells and tumor-associated neovasculature in PSMA-positive tumors.
      These results suggest the potential for further optimization of this novel vector
      in the context of therapeutic gene delivery.

PMID- 16453012
TI  - Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs
      during tumorigenesis.
AB  - The tumour-suppressor phosphatase with tensin homology (PTEN) is the most
      important negative regulator of the cell-survival signalling pathway initiated by
      phosphatidylinositol 3-kinase (PI3K). Although PTEN is mutated or deleted in many
      tumours, deregulation of the PI3K-PTEN network also occurs through other
      mechanisms. Crosstalk between the PI3K pathways and other tumorigenic signalling
      pathways, such as those that involve Ras, p53, TOR (target of rapamycin) or DJ1,
      can contribute to this deregulation. How does the PI3K pathway integrate signals
      from numerous sources, and how can this information be used in the rational
      design of cancer therapies?

PMID- 16453014
TI  - SIDS: genetic and environmental influences may cause arrhythmia in this silent
      killer.
AB  - In this issue of the JCI, Bowers et al. show that the common polymorphism of the
      cardiac voltage-gated sodium channel, type Valpha (SCN5A), designated S1103Y,
      found in African Americans is associated with an increased risk of sudden infant
      death syndrome (SIDS). Wild-type and mutant SCN5A channels both functioned
      typically under normal conditions in vitro, but exposure to acidic intracellular
      pH levels such as those found in respiratory acidosis--a known risk factor for
      SIDS--produced abnormal gain-of-function late reopenings of S1103Y channels,
      behavior that is often associated with cardiac arrhythmias. These pathologic late
      reopenings were suppressed by low levels of the channel-blocking drug mexiletine.
      These findings provide an excellent illustration of a causal relationship between
      the interaction of the environment and genetic background in SIDS and also raise
      interesting questions about the linkage of a genetic abnormality with a clinical
      phenotype.

PMID- 16453015
TI  - Gastrointestinal motility and glycemic control in diabetes: the chicken and the
      egg revisited?
AB  - Upper gastrointestinal dysfunction occurs frequently in diabetes and potentially
      contributes to both abdominal symptoms and impaired glycemic control; conversely,
      variations in blood glucose concentration reversibly affect gut motility in
      humans. In this issue of the JCI, Anitha et al. report apoptosis of rodent
      enteric neurons under hyperglycemic conditions, both in vitro and in vivo,
      associated with impaired PI3K activity and preventable by glial cell line-derived
      neurotrophic factor. These observations add to recent insights gained from animal
      models regarding the etiology of diabetic gastrointestinal dysfunction, but
      investigators must strive to translate animal data to human diabetes.

PMID- 16453013
TI  - Mechanisms of progression and regression of renal lesions of chronic
      nephropathies and diabetes.
AB  - The incidence of chronic kidney diseases is increasing worldwide, and these
      conditions are emerging as a major public health problem. While genetic factors
      contribute to susceptibility and progression of renal disease, proteinuria has
      been claimed as an independent predictor of outcome. Reduction of urinary protein
      levels by various medications and a low-protein diet limits renal function
      decline in individuals with nondiabetic and diabetic nephropathies to the point
      that remission of the disease and regression of renal lesions have been observed
      in experimental animals and even in humans. In animal models, regression of
      glomerular structural changes is associated with remodeling of the glomerular
      architecture. Instrumental to this discovery were 3D reconstruction studies of
      the glomerular capillary tuft, which allowed the quantification of sclerosis
      volume reduction and capillary regeneration upon treatment. Regeneration of
      capillary segments might result from the contribution of resident cells, but
      progenitor cells of renal or extrarenal origin may also have a role. This review
      describes recent advances in our understanding of the mechanisms and mediators
      underlying renal tissue repair ultimately responsible for regression of renal
      injury.

PMID- 16453016
TI  - Insulin's effect on the liver: "direct or indirect?" continues to be the
      question.
AB  - Previous studies suggest that insulin can inhibit hepatic glucose production
      (HGP) by both direct and indirect actions. The indirect effects include
      inhibition of glucagon secretion, reduction in plasma nonesterified fatty acid
      levels, reduction of the amount of gluconeogenic precursor supplied to the liver,
      and change in neural input to the liver. A study in this issue of the JCI
      demonstrates that, in overnight-fasted dogs, an acute, selective increase of
      portal insulin induces a rapid inhibition of HGP, and a 4-fold rise in head
      insulin level does not enhance the inhibition of HGP in response to portal
      insulin infusion. This study demonstrates that insulin's direct effects on the
      liver dominate the control of HGP. These data balance previous studies in mice
      that suggested that indirect effects of insulin via the hypothalamus are the
      primary determinant of HGP.

PMID- 16453017
TI  - C5a and Fcgamma receptors: a mutual admiration society.
AB  - Phagocytosis is a key process in protection of the host against pathogens and in
      provision of antigens for the immune response. Synergism between C3b and IgG and
      their receptors in promoting adherence to and then ingestion of an antigen has
      been recognized for decades. Only more recently, however, has cross-talk between
      another complement activation fragment, the anaphylatoxin C5a, and Fcgamma
      receptors (FcgammaRs) been defined. In this issue of the JCI, C5a is shown to
      signal, via its receptor, the upregulation of activating (proinflammatory-type)
      FcgammaRs. Moreover, engagement of FcgammaRs by the IgG-bearing immune complex
      instructs the cell to synthesize more C5, from which C5a is derived. Thus, this
      work establishes a feedback loop whereby FcgammaR expression and function are
      enhanced, a very desirable event in concert with an infection but potentially
      deleterious in autoimmunity.

PMID- 16453018
TI  - Mucus in chronic airway diseases: sorting out the sticky details.
AB  - Mucous hypersecretion is a major cause of airway obstruction in asthma, chronic
      obstructive pulmonary disease, and cystic fibrosis. EGFR ligands and IL-13 are
      known to stimulate mucous induction, but the detailed mechanisms of epithelial
      mucous regulation have not been well defined. In this issue of the JCI, Tyner et
      al. show, in a mouse model of chronic mucous hypersecretion, that ciliated
      epithelial cell apoptosis is inhibited by EGFR activation, allowing IL-13 to
      stimulate the differentiation of these cells into goblet cells, which secrete
      mucus. In defining this coordinated, 2-step process, we can consider the
      therapeutic effects of blocking mucous production. This begs the question, Is it
      possible to reduce airway obstruction in chronic lung disease by inhibiting EGFR
      activation and/or by inhibiting IL-13?

PMID- 16453019
TI  - Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13
      transdifferentiation signals.
AB  - Epithelial hyperplasia and metaplasia are common features of inflammatory and
      neoplastic disease, but the basis for the altered epithelial phenotype is often
      uncertain. Here we show that long-term ciliated cell hyperplasia coincides with
      mucous (goblet) cell metaplasia after respiratory viral clearance in mouse
      airways. This chronic switch in epithelial behavior exhibits genetic
      susceptibility and depends on persistent activation of EGFR signaling to PI3K
      that prevents apoptosis of ciliated cells and on IL-13 signaling that promotes
      transdifferentiation of ciliated to goblet cells. Thus, EGFR blockade (using an
      irreversible EGFR kinase inhibitor designated EKB-569) prevents virus-induced
      increases in ciliated and goblet cells whereas IL-13 blockade (using s-IL
      13Ralpha2-Fc) exacerbates ciliated cell hyperplasia but still inhibits goblet
      cell metaplasia. The distinct effects of EGFR and IL-13 inhibitors after viral
      reprogramming suggest that these combined therapeutic strategies may also correct
      epithelial architecture in the setting of airway inflammatory disorders
      characterized by a similar pattern of chronic EGFR activation, IL-13 expression,
      and ciliated-to-goblet cell metaplasia.

PMID- 16453020
TI  - Decreased vascular lesion formation in mice with inducible endothelial-specific
      expression of protein kinase Akt.
AB  - To determine whether endothelial Akt could affect vascular lesion formation,
      mutant mice with a constitutively active Akt transgene, which could be inducibly
      targeted to the vascular endothelium using the tet-off system (EC-Akt Tg mice),
      were generated. After withdrawal of doxycycline, EC-Akt Tg mice demonstrated
      increased endothelial-specific Akt activity and NO production. After blood flow
      cessation caused by carotid artery ligation, neointimal formation was attenuated
      in induced EC-Akt Tg mice compared with noninduced EC-Akt Tg mice and control
      littermates. To determine the role of eNOS in mediating these effects, mice were
      treated with N-nitro-L-arginine methyl ester (L-NAME). Neointimal formation was
      attenuated to a lesser extent in induced EC-Akt Tg mice treated with L-NAME,
      suggesting that some of the vascular protective effects were NO independent.
      Indeed, endothelial activation of Akt resulted in less EC apoptosis in ligated
      arteries. Immunostaining demonstrated decreased inflammatory and proliferative
      changes in induced EC-Akt Tg mice after vascular injury. These findings indicate
      that endothelial activation of Akt suppresses lesion formation via increased NO
      production, preservation of functional endothelial layer, and suppression of
      inflammatory and proliferative changes in the vascular wall. These results
      suggest that enhancing endothelial Akt activity alone could have therapeutic
      benefits after vascular injury.

PMID- 16453021
TI  - GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation
      of the PI3K/Akt pathway.
AB  - Diabetes can result in loss of enteric neurons and subsequent gastrointestinal
      complications. The mechanism of enteric neuronal loss in diabetes is not known.
      We examined the effects of hyperglycemia on enteric neuronal survival and the
      effects of glial cell line-derived neurotrophic factor (GDNF) on modulating this
      survival. Exposure of primary enteric neurons to 20 mM glucose (hyperglycemia)
      for 24 hours resulted in a significant increase in apoptosis compared with 5 mM
      glucose (normoglycemia). Exposure to 20 mM glucose resulted in decreased Akt
      phosphorylation and enhanced nuclear translocation of forkhead box O3a (FOXO3a).
      Treatment of enteric neurons with GDNF ameliorated these changes. In
      streptozotocin-induced diabetic mice, there was evidence of myenteric neuronal
      apoptosis and reduced Akt phosphorylation. Diabetic mice had loss of NADPH
      diaphorase-stained myenteric neurons, delayed gastric emptying, and increased
      intestinal transit time. The pathophysiological effects of hyperglycemia
      (apoptosis, reduced Akt phosphorylation, loss of inhibitory neurons, motility
      changes) were reversed in diabetic glial fibrillary acidic protein-GDNF (GFAP
      GDNF) Tg mice. In conclusion, we demonstrate that hyperglycemia induces neuronal
      loss through a reduction in Akt-mediated survival signaling and that these
      effects are reversed by GDNF. GDNF may be a potential therapeutic target for the
      gastrointestinal motility disorders related to diabetes.

PMID- 16453022
TI  - Drusen deposits associated with aging and age-related macular degeneration
      contain nonfibrillar amyloid oligomers.
AB  - Protein misfolding and aggregation are thought to underlie the pathogenesis of
      many amyloid diseases, such as Alzheimer and Parkinson diseases, whereby a
      stepwise protein misfolding process begins with the conversion of soluble protein
      monomers to prefibrillar oligomers and progresses to the formation of insoluble
      amyloid fibrils. Drusen are extracellular deposits found in aging eyes and in
      eyes afflicted with age-related macular degeneration (AMD). Recent
      characterizations of drusen have revealed protein components that are shared with
      amyloid deposits. However, characteristic amyloid fibrils have thus far not been
      identified in drusen. In this study, we tested the hypothesis that nonfibrillar
      oligomers may be a common link in amyloid diseases. Oligomers consisting of
      distinct amyloidogenic proteins and peptides can be detected by a recently
      developed antibody that is thought to recognize a common structure. Notably,
      oligomers exhibit cellular toxicity, which suggests that they play a role in the
      pathogenesis of neurodegenerative diseases. Through use of the anti-oligomer
      antibody, we came to observe the presence of nonfibrillar, toxic oligomers in
      drusen. Conversely, no reactivity was observed in age-matched control eyes
      without drusen. These results suggest that amyloid oligomers may be involved in
      drusen biogenesis and that similar protein misfolding processes may occur in AMD
      and amyloid diseases.

PMID- 16453023
TI  - Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel
      antiangiogenic activity of VEGF-A.
AB  - VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal
      neovascularization (CNV) incited by injury was increased by excess VEGF-A before
      injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic
      effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter
      via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP
      1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF
      E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A
      increased CNV before injury because VEGFR-1 activation was silenced by secreted
      protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC
      after injury revealed a temporal window in which VEGF-A signaling was routed
      principally through VEGFR-1. These observations indicate that therapeutic design
      of VEGF-A inhibition should include consideration of the level and activity of
      SPARC.

PMID- 16453024
TI  - A common cardiac sodium channel variant associated with sudden infant death in
      African Americans, SCN5A S1103Y.
AB  - Thousands die each year from sudden infant death syndrome (SIDS). Neither the
      cause nor basis for varied prevalence in different populations is understood.
      While 2 cases have been associated with mutations in type Valpha, cardiac voltage
      gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS
      prevalence, consistent with a role for environmental influences in disease
      pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases
      were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were
      carriers of the heterozygous genotype, which was previously associated with
      increased risk for arrhythmia in adults. This suggests that infants with 2 copies
      of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were
      found to operate normally under baseline conditions in vitro. As risk factors for
      SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were
      subjected to lowered intracellular pH. Only Y1103 channels gained abnormal
      function, demonstrating late reopenings suppressible by the drug mexiletine. The
      variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene
      environment interaction. Overall, homozygous and rare heterozygous SCN5A missense
      variants were found in approximately 5% of cases. If our findings are replicated,
      prospective genetic testing of SIDS cases and screening with counseling for at
      risk families warrant consideration.

PMID- 16453025
TI  - Cell-derived anaphylatoxins as key mediators of antibody-dependent type II
      autoimmunity in mice.
AB  - Complement C5a, a potent anaphylatoxin, is a candidate target molecule for the
      treatment of inflammatory diseases, such as myocardial ischemia/reperfusion
      injury, RA, and the antiphospholipid syndrome. In contrast, up until now, no
      specific contribution of C5a and its receptor, C5aR, was recognized in diseases
      of antibody-dependent type II autoimmunity. Here we identify C5a as a novel key
      mediator of autoimmune hemolytic anemia (AIHA) and show that mice lacking C5aR
      are partially resistant to this IgG autoantibody-induced disease model. Upon
      administration of anti-erythrocyte antibodies, upregulation of activating Fcgamma
      receptors (FcgammaRs) on Kupffer cells, as observed in WT mice, was absent in
      C5aR-deficient mice, and FcgammaR-mediated in vivo erythrophagocytosis was
      impaired. Surprisingly, in mice deficient in FcgammaRI and FcgammaRIII, anti
      erythrocyte antibody-induced C5 and C5a production was abolished, demonstrating
      the existence of a previously unidentified FcgammaR-mediated C5a-generating
      pathway. These results show that the development of a full-blown antibody
      dependent autoimmune disease requires C5a--produced by and acting on FcgammaR-
      and may suggest therapeutic benefits of C5 and/or C5a/C5aR blockade in AIHA and
      other diseases closely related to type II autoimmune injury.

PMID- 16453026
TI  - Insulin's direct effects on the liver dominate the control of hepatic glucose
      production.
AB  - Insulin inhibits glucose production through both direct and indirect effects on
      the liver; however, considerable controversy exists regarding the relative
      importance of these effects. The first aim of this study was to determine which
      of these processes dominates the acute control of hepatic glucose production
      (HGP). Somatostatin and portal vein infusions of insulin and glucagon were used
      to clamp the pancreatic hormones at basal levels in the nondiabetic dog. After a
      basal sampling period, insulin infusion was switched from the portal vein to a
      peripheral vein. As a result, the arterial insulin level doubled and the hepatic
      sinusoidal insulin level was reduced by half. While the arterial plasma FFA level
      and net hepatic FFA uptake fell by 40-50%, net hepatic glucose output increased
      more than 2-fold and remained elevated compared with that in the control group.
      The second aim of this study was to determine the effect of a 4-fold rise in head
      insulin on HGP during peripheral hyperinsulinemia and hepatic insulin deficiency.
      Sensitivity of the liver was not enhanced by increased insulin delivery to the
      head. Thus, this study demonstrates that the direct effects of insulin dominate
      the acute regulation of HGP in the normal dog.

PMID- 16453030
TI  - Cofactor biosynthesis: an organic chemist's treasure trove.

PMID- 16453031
TI  - Marine natural products.
AB  - This review covers the literature published in 2004 for marine natural products,
      with 693 citations (491 for the period January to December 2004) referring to
      compounds isolated from marine microorganisms and phytoplankton, green algae,
      brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates
      and echinoderms. The emphasis is on new compounds (716 for 2004), together with
      their relevant biological activities, source organisms and country of origin.
      Biosynthetic studies (8), and syntheses (80), including those that lead to the
      revision of structures or stereochemistries, have been included.

PMID- 16453027
TI  - Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic
      esophagitis.
AB  - Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood
      pathogenesis. In order to define disease mechanisms, we took an empirical
      approach analyzing esophageal tissue by a genome-wide microarray expression
      analysis. EE patients had a striking transcript signature involving 1% of the
      human genome that was remarkably conserved across sex, age, and allergic status
      and was distinct from that associated with non-EE chronic esophagitis. Notably,
      the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known
      as CCL26) was the most highly induced gene in EE patients compared with its
      expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein
      levels strongly correlated with tissue eosinophilia and mastocytosis.
      Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was
      associated with disease susceptibility. Finally, mice deficient in the eotaxin
      receptor (also known as CCR3) were protected from experimental EE. These results
      implicate eotaxin-3 as a critical effector molecule for EE and provide insight
      into disease pathogenesis.

PMID- 16453032
TI  - Marine natural products: synthetic aspects.
AB  - An overview of marine natural products synthesis during 2004 is provided. As with
      the previous installment of this series, the emphasis is on total syntheses of
      molecules of contemporary interest, new total syntheses, and syntheses that have
      resulted in structure confirmation or stereochemical assignments.

PMID- 16453033
TI  - Steroids: partial synthesis in medicinal chemistry.
AB  - This article reviews the progress in the chemistry of the steroids that was
      published between January and December 2004. The reactions and partial synthesis
      of estrogens, androgens, pregnanes, cholic acid derivatives, cholestanes and
      vitamin D analogues are covered. There are 127 references.

PMID- 16453034
TI  - Metabolites from Eutypa species that are pathogens on grapes.
AB  - Structural and synthetic studies of the metabolites isolated from Eutypa lata are
      reviewed. This fungus is the causative agent of Eutypa dieback disease, also
      known as eutyposis or dying-arm disease, a perennial canker that affects
      grapevines and many other woody fruit plants. The review, which encompasses all
      the literature in this field up to the present and in which 76 references are
      cited, also includes a detailed study of the biological activity of the
      metabolites, especially the role of toxins in the development of the plant
      disease. Some aspects of the synthesis and biosynthesis of these metabolites and
      related compounds are discussed.

PMID- 16453036
TI  - Making $ense of growth hormone therapy for normal short children.

PMID- 16453035
TI  - Natural products from medicinal plants: non-alkaloidal natural constituents of
      the Thalictrum species.
AB  - Thalictrum is an important plant genus that is widely used in traditional
      medicine. In this review considerable attention has been given to triterpenoid
      saponins in connection with their specific distribution in the Thalictrum genus
      and with their biological activity. All other non-alkaloid compounds isolated
      from the Thalictrum genus are also reviewed; these metabolites are discussed in
      relation to their structural features and to their role in the plants.

PMID- 16453037
TI  - The inaugural centennial lecture: celebrating milestones achieved and pondering
      the road ahead.

PMID- 16453038
TI  - 2005 Runme Shaw Memorial Lecture: Training doctors for the 21st century--a global
      perspective.

PMID- 16453039
TI  - 2005 Galloway Memorial Lecture: Breast phyllodes tumours--morphology and beyond.
AB  - OBJECTIVES: The aims of this study were to evaluate the predictive role of
      morphology in a series of breast phyllodes tumours (PTs) in Asian women, and to
      determine the utility of immunohistochemical expression of p53 and CD117 in the
      stromal component. MATERIALS AND METHODS: Breast PTs, diagnosed between January
      1992 and December 2002 at the Department of Pathology, Singapore General
      Hospital, were classified into benign, borderline and malignant categories.
      Surgical margins were evaluated as complete or diffusely involved. Patient follow
      up was obtained from casenotes and the Singapore Cancer Registry. Tissue
      microarrays (TMAs) were constructed using the 2-mm punch on the Beecher arrayer.
      p53 and CD117 immunohistochemistry was applied on 4-microm sections cut from TMA
      blocks. Immunostaining intensity was graded as 0, 1+, 2+ or 3+, for nil, weak,
      moderate and strong reactivity. The proportion of stromal cells decorated was
      assessed. Statistical analysis utilised the software SPSS for windows 11.5.
      Survival curves were plotted using the Kaplan-Meier method, while multivariate
      analysis was accomplished using the stepwise Cox proportional hazards model. A P
      value of <0.05 was considered a significant result. For verification of protein
      expression results, a pure stromal population derived from laser capture
      microdissection was subjected to real-time polymerase chain reaction to determine
      p53 and CD117 mRNA upregulation. RESULTS: Three hundred thirty-five women
      diagnosed with PT were aged 16 to 69 years (median, 42 years). Tumour size ranged
      from 0.9 to 25 cm (median, 4 cm). Histologic classification revealed 250 (74.6%)
      benign, 54 (16.1%) borderline and 31 (9.3%) malignant PTs. Surgical margins were
      focally involved in 186 (55.5%) cases, diffusely affected in 9 (2.9%) cases and
      complete in 139 (41.5%) cases. Stromal cells positively stained ranged from 1% to
      80% (mean, 15%; median, 5%) for p53, and 1% to 25% for CD117 (mean, 8%; median,
      3%). p53 and CD117 staining was associated with PT grade (P = 0.004, P <0.001).
      Forty-three (12.8%) women suffered 57 recurrences (mean and median follow-up of
      30.3 and 20.4 months respectively). Nine (2.7%) died during follow-up, 7 from
      malignant disease (mean and median survival duration 37.6 and 23.6 months
      respectively). Complete margins (P = 0.033) resulted in reduced recurrence risk
      by 51.7%. Though tumour grade was associated with an increased hazard of 1.63, it
      was not significant (P = 0.28). Immunoexpression of p53 was not associated with
      recurrence (P = 0.447), while CD117 was (P = 0.001). Upregulation of p53 and
      CD117 mRNA was found in cases in which there was protein overexpression.
      CONCLUSIONS: Involved surgical margins remain a key prognostic parameter in
      breast PT. Death from disease occurred in women with malignant PTs at
      presentation, underscoring the need to manage this group more aggressively. p53
      staining can be used to corroborate malignancy in PT. CD117 was predictive of
      recurrence, and if further validated, its expression can be explored for
      therapeutic purposes. Preliminary molecular studies verify mRNA upregulation in
      p53 and CD117 overexpressed cases.

PMID- 16453040
TI  - 2005 Distinguished Academician Lecture: Evolution of postgraduate medical
      education in Singapore--role of professional associations.
AB  - From 1910 to 1945, doctors in Singapore received postgraduate training through
      apprenticeship. During the early post-war period, some doctors in the public
      service were given scholarships to study in Britain and to obtain higher
      professional qualifications from the British Royal Colleges. The events that most
      influenced subsequent development of postgraduate education in Singapore occurred
      between 1956 and 1969: the formation of the Academy of Medicine and the Singapore
      Medical Association (SMA); organisation of courses for candidates preparing for
      examinations of the Royal Australasian and British Colleges; competition between
      the Academy and the University over responsibility for postgraduate medical
      education; the inauguration of the School of Postgraduate Medical Studies (SPMS);
      and the introduction of Master of Medicine (M Med) degrees in various medical
      specialties. From 1970 to 1999, there was expansion in several aspects of
      postgraduate medical education: SPMS awarded more than 2000 M Med degrees; the
      Singapore Medical Council (SMC) established a Register of Specialists and formed
      a Specialist Accreditation Board; the Academy formed Chapters in 10 specialties
      and developed Advanced Specialty Training programmes leading to Fellowship of the
      Academy of Medicine Singapore (FAMS); the SMA formed Societies in some 20
      specialties; and a College of Family Physicians was inaugurated. There have been
      more developments from 2000 to 2005: the University restructured SPMS as a
      Division of Graduate Medical Studies within the Faculty of Medicine; the SMC
      implemented compulsory Continuing Medical Education; and the Academy converted 6
      of its 10 Chapters into Colleges.

PMID- 16453041
TI  - 2005 Young Investigator's Award Winner: Assessment of diastolic function in newly
      diagnosed hypertensives.
AB  - INTRODUCTION: The prevalence and severity of diastolic dysfunction (DD) among
      newly diagnosed hypertensives (NDHT) is not fully established. The aim of this
      study was to evaluate left ventricular diastolic function (LVDF) in patients with
      NDHT. MATERIALS AND METHODS: This study involved 396 subjects (198 NDHT, age and
      gender matched 198 normotensives; age, 30 to 50 years). Parameters of LVDF
      included Doppler-echocardiographic measurements of peak early (E) and late (A)
      diastolic velocities, E-wave deceleration time (DT) and isovolumetric relaxation
      time (IVRT). E/A ratio of <1 was taken as an indicative of DD. RESULTS: Patients
      with NDHT had reduced E/A ratio (1.27 +/- 0.41 vs 1.37 +/- 0.35, P <0.001) and
      shortened DT (180.0 +/- 40.0 ms vs 190.0 +/- 30.0 ms, P = 0.025). The peak A
      velocity and IVRT were increased in the NDHT group [(62.73 +/- 13.82 ms vs 58.26
      +/- 12.40 ms, P = 0.002) and (90.0 +/- 20.0 ms vs 80.0 +/- 10.0 ms, P <0.001),
      respectively]. Peak E velocity was similar in both groups. The prevalence of DD
      was increased in the NDHT group, 18.6% (32) vs 3.4% (6), P <0.001. Of the 32 NDHT
      subjects who had DD, 84.4% (27) had no left ventricular hypertrophy (LVH) and
      15.7% (5) had LVH. Diastolic function was negatively correlated with age, body
      mass index, systolic blood pressure, diastolic blood pressure and left
      ventricular mass index. CONCLUSION: Impairment in LVDF occurs in NDHT which may
      precede structural abnormalities. Hypertension, obesity, older age and LVH are
      associated with worsening of diastolic function.

PMID- 16453042
TI  - 15th Seah Cheng Siang Memorial Lecture: Liver transplantation--lessons learnt and
      future horizons.
AB  - The first clinical successes with liver transplantation by Starzl in 1967 were
      based on studies showing that in man, organ allografts could induce self
      tolerance with the aid of immunosuppression. Overall survival figures were poor
      until 1983, when cyclosporine was introduced into immunosuppressive regimes, and
      with the introduction of tacrolimus, results improved even further. With figures
      for 1-year survival now up to 90%, more attention is being directed to quality of
      life and the side effects of immunosuppression. Nephrotoxicity along with
      hypertension and diabetes are of major concern, and a significant number of long
      term liver transplant patients are now facing end-stage renal failure. In the
      majority of conditions transplanted there is also a significant chance of disease
      recurrence in the graft. Owing to the shortage of cadaver organs, split liver and
      domino techniques are increasingly utilised. Living donor liver transplantation
      has also come to the fore, and to minimise potential harm to the donor, new
      techniques are being developed which will allow greater use of left lobe grafts.

PMID- 16453043
TI  - Inaugural Lecture of the College of Surgeons, Singapore: Of role and role model
      (a college takes its first steps towards collective and individual excellence in
      the 21st century).

PMID- 16453044
TI  - 10th Yahya Cohen Memorial Lecture: Clinical predictors in obstructive sleep
      apnoea patients with computer-assisted quantitative videoendoscopic upper airway
      analysis.
AB  - AIM: To identify the clinical predictors and assist surgeons in their clinical
      management of obstructive sleep apnoea (OSA) - a prospective study with a new
      approach to analyse the static and dynamic upper airway morphology between
      patients with OSA and normal subjects. To introduce a new method of assessment
      for surgical outcome. MATERIALS AND METHODS: Quantitative computer-assisted
      videoendoscopy (validated with upper airway magnetic resonance imaging) was
      performed in 49 (43 males, 6 females) patients with OSA and compared with 39 (22
      males, 17 females) controls (apnoea-hypopnoea index <5). Absolute cross-sectional
      areas, transverse and longitudinal diameters at the retro-palatal and retro
      lingual levels were measured during end of quiet respiration and during Mueller's
      manoeuvre in the erect and supine positions, allowing us to study static and
      dynamic morphology (collapsibility) of the upper airway. We analysed 3744
      parameters. RESULTS: In males, retro-palatal and retro-lingual areas during
      Mueller's manoeuvre in the supine position of 0.7981 cm2 [receiver operating
      characteristics (ROC) = 0.9284, positive predictive value (PPV) = 86.05%,
      negative predictive value (NPV) = 84.62%] and 2.0648 cm2 (ROC = 0.8183, PPV =
      76%, NPV = 83.33%), respectively, were found to be good predictors/ cut-off
      values for OSA. Retro-palatal area measured in the supine position during
      Mueller's manoeuvre (AS1M) and collapsibility of retro-palatal area in the supine
      position calculated (CAS1) were found to have significant correlations with
      severity of OSA. In females, areas measured during Mueller's manoeuvre in the
      supine position of 0.522 cm2 at retropalatal level (ROC = 1, 100% PPV and NPV)
      and transverse diameter at retro-lingual level during erect Mueller's manoeuvre
      of 1.1843 cm (ROC = 0.9056, PPV = 100%, NPV = 83.33%) were found to be
      predictive. All measurements at the retro-palatal level and in the supine
      position had higher predictability. Area measurements obtained during Muller's
      manoeuvre were more predictive (ROC >0.9910) than resting measurements (ROC
      >0.8371). Several gender and anatomical-site specific formulas with excellent
      predictability (ROC close or equal to 1) were also devised. Examples of surgical
      outcome assessment were introduced. CONCLUSION: Upper airway Mueller's studies
      are predictive and useful (independent samples t-test/Mann Whitney U test, ROC)
      in identifying patients with OSA. With these gender and anatomical-site specific
      OSA predictors/formulas and this innovative clinical method, we hope to assist
      other surgeons with quantitative clinical diagnosis, assessment, surgical
      planning and outcome assessment tools for OSA patients.

PMID- 16453045
TI  - Continuing professional development--supporting the delivery of quality
      healthcare.
AB  - Patients and the general public have a right to expect that doctors remain up to
      date and are professionally competent. The ultimate aim of continuing
      professional development (CPD) is to contribute to high-quality patient care. The
      General Medical Council in the UK has published guidance in relation to standards
      for CPD, appraisal and revalidation. Doctors in the UK participate in an annual
      appraisal, the outcome of which is the development of the Personal Development
      Plan. This paper describes a framework for effective CPD and includes methods of
      self-assessment of clinical practice. Contributions to effective CPD come from 3
      sources--doctors, CPD providers and accrediting bodies. The CPD system of
      recording credits currently in use by the Royal Colleges of Physicians in the UK
      is also described.

PMID- 16453046
TI  - Should general physicians or subspecialists undertake acute medical care in
      public hospitals?
AB  - Acute medical care in public hospitals may be handled differently in different
      countries. As general physicians in Singapore are trained to deal with
      undifferentiated clinical problems and run most of the admitting wards, they are
      suited to take care of patients with acute medical problems. The exceptions to
      this rule are made for patients accurately diagnosed with stroke and acute
      coronary syndrome, who have better clinical outcomes if admitted directly to
      stroke units and coronary care units respectively. In the diagnostic workup,
      general physicians are trained to practise probabilistic medicine, and thus to
      order more focused investigations to rule in or rule out certain diagnoses. The
      subspecialist is more inclined to exclude possible diagnoses in his or her field.
      Once there is a clear-cut diagnosis, for primary care, it is up to the patient to
      decide if his primary doctor should be a generalist or subspecialist. An
      important role for the general physicians who manage patients with multiple
      diseases is constant medication review to shorten the list of drugs.

PMID- 16453050
TI  - Citation on Dr Chew Chin Hin for admission to Honorary Fellowship, College of
      Physicians Singapore on 2 July 2005.

PMID- 16453051
TI  - Hematological response to short-term oral cyanocobalamin therapy for the
      treatment of cobalamin deficiencies in elderly patients.
AB  - OBJECTIVES: The aim of this trial was to demonstrate the efficacy of one month of
      oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin
      deficiency related to food-cobalamin malabsorption (FCM). PATIENTS AND METHOD:
      Twenty elderly patients (mean age: 78+/-17 years) with established cobalamin
      deficiency related to FCM were included in an open-label, non-randomized, non
      placebo trial. They were treated with a maximum of 1,000 microgram per day of
      oral crystalline cyanocobalamin for at least 1 month. Serum cobalamin levels
      (primary endpoint), blood count abnormalities and reticulocytes count (secondary
      endpoints) were determined at baseline and during the first month of treatment.
      RESULTS: 85% of the patients normalized their serum cobalamin levels with a mean
      increase of+167 pg/ml (p<0.001 compared with baseline). 100% of the patients
      corrected their initial macrocytosis and 25% their anemia; 100% of the patients
      had medullar regeneration with a mean increase of reticulocytes count of 32+/
      11.3 x 106/l (p=0.03 compared with baseline). CONCLUSIONS: Our findings support
      the view that one month of oral crystalline cyanocobalamin is effective to
      correct serum vitamin B12 levels and to obtain hematological responses in elderly
      patients with cobalamin deficiency related to FCM.

PMID- 16453052
TI  - Associations between meat consumption and the prevalence of degenerative
      arthritis and soft tissue disorders in the adventist health study, California
      U.S.A.
AB  - OBJECTIVE: To examine associations between the prevalence of degenerative
      arthritis and soft tissue disorders and consumption of meat and other foods among
      participants in the Adventist Health Study. METHODS: Unconditional logistic
      regression analysis is used to examine cross-sectional associations, adjusting
      for the effects of age, smoking, alcohol consumption, body mass index, use of sex
      hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft
      tissue disorders was 22.60 percent. Women had a higher prevalence than men and
      prevalence increased greatly with age. Smoking, higher body mass index, never use
      of contraceptive pills, and current hormone replacement therapy are associated
      with a higher prevalence of these disorders on multivariate analysis.
      Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the
      reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in
      women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and
      fruit consumption were weakly associated with increased risk. There were
      protective associations with nut and salad consumption. CONCLUSIONS: Greater meat
      consumption is associated with a higher prevalence of degenerative arthritis and
      soft tissue disorders in both male and female subjects of this population, as is
      hormone replacement therapy in women.

PMID- 16453053
TI  - Community organized food and nutrition education: participation, attitudes and
      nutritional risk in seniors.
AB  - Evergreen Action Nutrition (EAN) is a health promotion program designed to
      facilitate relatively healthy members of a seniors recreation center to maintain
      their nutritional health as they age. A main goal of this project was to
      demonstrate the feasibility and relevance of using the community organization
      approach to develop a nutrition education program for seniors. METHODS: Using the
      current membership list, seniors were randomly selected to receive a mailed
      baseline (n=247) questionnaire. A follow-up survey (n=251) was sent out to
      randomly selected members three years later to determine participation in EAN and
      reported behavior change. Although not the same individuals, responses were
      compared to baseline to determine changes in nutritional risk. Items from the
      Diet and Health Knowledge survey were compared by EAN participation. RESULTS: The
      program had a large reach with 162 survey respondents (64.5%) reporting some
      level of participation and 51% reporting "frequent" participation. Use of
      informal forms of education predominated (e.g. displays). Significant differences
      were found between baseline and follow-up for risk attributed to low intake of
      fruits and vegetables and frequency of eating, with EAN participants having
      reduced risk of low fruit and vegetable intake. Those participating in formal
      education (e.g. food workshops) reported more frequent changes in food practices
      than those participating in informal activities. EAN participants appear to have
      more healthy nutrition attitudes/beliefs. CONCLUSION: The community organization
      approach to program planning and delivery leads to the development of diverse and
      appropriate nutrition education activities for seniors. Informal and formal
      health promotion activities can be successfully implemented in recreation
      centers.

PMID- 16453054
TI  - Effectiveness of a community based low intensity exercise program for older
      adults.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness of a community
      based, low-intensity exercise programme in older adults from socio-economically
      and historically disadvantaged communities. DESIGN: Three community centres were
      selected: two were allocated to the same 20-week, twice-weekly exercise program
      (EX1, n=38; EX2, n=32); and a third to relaxation classes (control/CTL; n=21).
      Measurements at baseline, 10 and 20 weeks included field tests for anthropometry,
      static and dynamic balance, gait, upper and lower body strength, 6-minute walk
      test, blood pressure, activities of daily living (ADL), instrumental activities
      of daily living (IADL), physical activity recall and self perceived health
      status. RESULTS: Exercise training significantly improved dynamic balance in both
      groups (75.1+/-31.5 vs 55.3+/-13.6 s, and 53.3+/-17.0 vs 37.0+/-10.4 s, for EX1
      and EX2, respectively, p < 0.001 compared to CTL (57+/-27 vs 53+/-15 s). Lower
      body strength, as measured by the number of sit-to-stand repetitions in 10 s was
      also significantly improved in both EX1 and EX2 (p<0.001). No significant changes
      occurred in the CTL group. Systolic blood pressure decreased in both EX1 and EX2
      from baseline to 20 weeks (147.8+/-12.8 vs 143.9+/-3.3 mmHg and 143.0+/-13.9 vs
      137.4+/-14.5 mmHg, respectively, p<0.009, compared to CTL (147+/-13 to 150+/-16
      mmHg). Furthermore, in a sub sample of subjects who were hypertensive at the
      outset, exercise intervention was associated with a significant decrease in
      systolic blood pressure (n=26; 146+/-14 mmHg to 140+/-14 mmHg; p=0.005).
      Variables unaffected by exercise training were upper body strength, body
      composition and fat distribution, 20 m walk, cardiovascular endurance, time spent
      in recreational activities, self perceived health status and ADL. CONCLUSION: A
      community-based, low intensity exercise programme improved dynamic balance and
      lower body strength in community dwelling older adults and improved blood
      pressure, particularly in those who were hypertensive.

PMID- 16453055
TI  - Leukoaraiosis is associated with functional impairment in older patients with
      Alzheimer's disease but not vascular dementia.
AB  - BACKGROUND: Leukoaraiosis (LA) is a common finding in older persons, and might be
      associated with reduced cognitive performance, gait abnormalities, and functional
      impairment. Although LA is more frequent in persons affected by dementia, scant
      data are available about its clinical consequences in this group of patients.
      OBJECTIVE: To study the association between presence of LA and functional
      performance in basic activities of daily living in a sample of older persons
      affected by dementia. DESIGN: We conducted a cross-sectional study on 214
      patients; 77 affected by late onset Alzheimer's disease (LOAD), and 137 by
      vascular dementia (VD). Functional status was assessed using Barthel Index (BI).
      LA was assessed using computed tomography. RESULTS: In LOAD patients, LA (OR:
      7.87; 1.26-48.94), and MMSE score (OR: 0.83; 0.71-0.98) were associated with the
      risk of severe disability, independent of age, gender, diabetes, hypertension,
      coronary heart disease, left ventricular hypertrophy, atrial fibrillation, and
      brain atrophy. In VD patients, MMSE score (OR: 0.77; 0.64-0.93), and CHD (OR:
      7.41; 1.09-50.21), but not LA (OR: 2.07; 0.45-9.45) were associated with a severe
      functional impairment after multivariate adjustment. CONCLUSIONS: Our study
      suggests that LA might be associated with a worse functional status in basic
      activities of daily living in patients affected by LOAD but not VD. LA might act
      synergistically with cognitive and behavioural disturbances to the onset and
      progression of disability of these patients.

PMID- 16453056
TI  - A cross-sectional study of vitamin C and cognitive function in older adults: the
      differential effects of gender.
AB  - Previous studies have suggested that vitamin C status may be associated with
      cognitive function in community-dwelling populations. However, this has not been
      consistent across all studies due to methodological differences. This cross
      sectional study assessed the association between vitamin C and cognitive function
      in 544 community-dwelling older adults aged 65 or older who participated in both
      the Cardiovascular Health Study (CHS) and the CLUE II study in 1989. Three
      percent of the subjects had low plasma vitamin C concentrations (< 40 mg/dL) and
      15% had low total vitamin C intake (< 60 mg/day). Most participants (96.7
      percent) had normal cognitive function. In the unadjusted analyses, the highest
      fifth of plasma vitamin C concentration was associated with better Digit Symbol
      Substitution Test (DSST) scores and marginally associated with Mini-Mental State
      Examination (MMSE) compared to the lowest fifth. Total vitamin C intake, measured
      by Block's food frequency questionnaire, was generally associated with higher
      MMSE scores, though it was not significant. Adjusting for numerous factors did
      not substantially change results. In a stratified analysis by gender, higher
      plasma concentrations or intake were associated with higher MMSE scores for men
      but not for women. These mixed results do not provide strong evidence of an
      association between vitamin C concentrations or intake and cognitive function.

PMID- 16453057
TI  - Nutritional, functional and psychosocial correlates of disability among older
      adults.
AB  - PURPOSE: The purpose of the present study was to examine the nutritional,
      functional and psychosocial correlates of disability among 54 older adults aged
      65 years of age or older. METHODS: Using validated questionnaires and tests,
      nutritional risk (Mini-Nutritional Assessment), functional capacity (mobility,
      balance, endurance, grip strength and lower extremity strength), the psychosocial
      factors (life satisfaction, depression, and social support) and level of
      disability of the participants were examined. RESULTS: The study showed that
      functional mobility was the strongest correlate of disability, even after
      controlling for age, gender and residential living status (p<.05). Life
      satisfaction and nutrition risk had marginal significance as being related to
      disability. CONCLUSION: The results of the present study have implications for
      the development of evidence-based health promotion interventions for older
      adults.

PMID- 16453058
TI  - Slow dark deactivation of Arabidopsis chloroplast ATP synthase caused by a
      mutation in a nonplastidic SAC domain protein.
AB  - Coupling factor slow recovery (cfs) is a recessive mutant of Arabidopsis with
      anomalous ATP synthase activation/deactivation characteristics as well as a
      distinct growth phenotype. The most significant feature of this mutant is that
      the dark-adapted deactivation of ATP synthase is a very slow relative to the wild
      type, indicating interference with ATP synthase regulation. Physical mapping of
      the mutation delimited it to a region in a pair of bacterial artificial
      chromosome clones. Examination of T-DNA insertion lines of all 34 putative genes
      located in this region identified two homozygous T-DNA insertion lines of the
      same gene, At3g59770, possessing phenotypes indistinguishable from the cfs
      mutant. At3g59770 had been previously identified as suppressor of actin 9 (SAC9),
      a protein with a SAC domain, a protein-protein interaction module containing two
      conserved tryptophans known as a WW domain, and an ATP/GTP-binding site motif A.
      Sequence analysis of cfs revealed a point mutation of G to A resulting in an
      amino acid substitution from tryptophan to STOP, thereby coding a truncated
      protein. Real-time-PCR amplification of the gene specific fragments showed that
      the T-DNA mutants did not have full-length transcripts whereas the cfs mutant
      transcribed a full-length mutated transcript. Further investigation of SAC9 RNA
      expression levels in different tissues of wild-type plants by RT-PCR revealed the
      highest expression in leaves. SAC 9 dysfunction interferes with ATP synthase
      deactivation, possibly by an alteration in phosphoinositide signaling inducing a
      stress mimicry response.

PMID- 16453059
TI  - Photosynthesis in the Archean era.
AB  - The earliest reductant for photosynthesis may have been H2. The carbon isotope
      composition measured in graphite from the 3.8-Ga Isua Supercrustal Belt in
      Greenland is attributed to H2-driven photosynthesis, rather than to oxygenic
      photosynthesis as there would have been no evolutionary pressure for oxygenic
      photosynthesis in the presence of H2. Anoxygenic photosynthesis may also be
      responsible for the filamentous mats found in the 3.4-Ga Buck Reef Chert in South
      Africa. Another early reductant was probably H2S. Eventually the supply of H2 in
      the atmosphere was likely to have been attenuated by the production of CH4 by
      methanogens, and the supply of H2S was likely to have been restricted to special
      environments near volcanos. Evaporites, possible stromatolites, and possible
      microfossils found in the 3.5-Ga Warrawoona Megasequence in Australia are
      attributed to sulfur-driven photosynthesis. Proteobacteria and protocyanobacteria
      are assumed to have evolved to use ferrous iron as reductant sometime around 3.0
      Ga or earlier. This type of photosynthesis could have produced banded iron
      formations similar to those produced by oxygenic photosynthesis. Microfossils,
      stromatolites, and chemical biomarkers in Australia and South Africa show that
      cyanobacteria containing chlorophyll a and carrying out oxygenic photosynthesis
      appeared by 2.8 Ga, but the oxygen level in the atmosphere did not begin to
      increase until about 2.3 Ga.

PMID- 16453062
TI  - Molecular insights into the origins of the Shompen, a declining population of the
      Nicobar archipelago.
AB  - The Shompen, one of the most isolated and poorly understood contemporary hunter
      gatherer populations, inhabit Great Nicobar Island, the southernmost island of
      the Nicobar archipelago. Morphological imprints in the Shompen were interpreted
      to favour a mixed Indo-Chinese, Malay, Negrito and Dravidian origin. Analyses of
      the mitochondrial, Y-chromosomal and autosomal gene pool of contemporary Shompen
      have revealed low diversity, illustrating a founder effect in the island
      population. Mitochondrial sequence analyses revealed the presence of two
      haplogroups of R lineage: B5a, and a newly defined clade, R12. Y-chromosomal
      analyses demonstrated the occurrence of a single lineage found predominantly in
      Austro-Asiatic speakers across Asia. With the different types of genetic markers
      analysed, the Shompen exhibit varying levels of genetic relatedness with the
      Nicobarese, and Austro-Asiatic speakers of mainland India and Southeast Asia.
      These genetic analyses provide evidence that the Shompen, an offshoot of the
      Nicobarese, are descendants of Mesolithic hunter-gatherers of Southeast Asian
      origin, deriving from at least two source populations.

PMID- 16453061
TI  - The regulatory role of residues 226-232 in phosphoenolpyruvate carboxylase from
      maize.
AB  - The regulatory properties of maize phosphoenolpyruvate carboxylase were
      significantly altered by site-directed mutagenesis of residues 226 through 232.
      This conserved sequence element, RTDEIRR, is part of a surface loop at the dimer
      interface. Mutation of individual residues in this sequence caused various
      kinetic changes, including desensitization of the enzyme to key allosteric
      effectors or alteration of the K(0.5 PEP) for the substrate phosphoenolpyruvate.
      R231A, and especially R232Q, displayed decreased apparent affinity for the
      activator glucose-6-phosphate. Apparent affinity for the activator glycine was
      reduced in D228N and R232Q, while the maximum activation caused by glycine was
      greatly reduced in R226Q and E229A. R226Q and E229A also showed significantly
      lower sensitivity to the inhibitors malate and aspartate. E229A exhibited a low
      K(0.5 PEP), while the K(0.5 PEP )of R232Q was significantly higher than that of
      wild type. Thus these seven residues are critical determinants of the enzyme's
      kinetic responses to activators, inhibitors and substrate. The present results
      support an earlier suggestion that Arg 231 contributes to the binding site of the
      allosteric activator glucose-6-phosphate, and are consistent with other proposals
      that the substrate phosphoenolpyruvate allosterically activates the enzyme by
      binding at or near the glucose-6-phosphate site. The results also suggest that
      the glycine binding site may be contiguous with the glucose-6-phosphate binding
      site. Glu 229, which extends from this interface region through the interior of
      the protein and emerges near the aspartate binding site, may provide a physical
      link for propagating conformational changes between the allosteric activator and
      inhibitor binding regions.

PMID- 16453063
TI  - Biochemical data in ornithine transcarbamylase deficiency (OTCD) carrier risk
      estimation: logistic discrimination and combination with genetic information.
AB  - One-fifth of the gene mutations causing ornithine transcarbamylase deficiency
      cannot be detected. In such cases carrier risk estimation must refer to
      biochemical data-such as increased plasma glutamine concentration or increased
      orotidine excretion after allopurinol load -although these parameters do not
      yield a definite diagnosis. Here, I derive odds for carrier risk estimation from
      published data, i.e. from mean and standard deviation of glutamine concentrations
      in carriers and noncarriers, assuming normal distributions, and from allopurinol
      test results in individual carriers and noncarriers using logistic regression. I
      show how such biochemical information may be combined with genetic information,
      thus demonstrating the usefulness of biochemical data. The necessity to assess
      individual results in larger proband groups and to consider possible correlations
      between different parameters is indicated.

PMID- 16453065
TI  - Heavy metal profile in five fish species included in human diet, domiciled in the
      end flow of river Neretva (Croatia).
AB  - Concentration of three heavy metals (mercury (Hg), lead, (Pb), and cadmium, (Cd))
      and one metalloid (arsenic [As]), were determined by atomic absorption
      spectrophotometry in five tissues (muscles, liver, kidneys, gills, and gonads) of
      five fish species (carp-Cyprinus carpio, tench-Tinca tinca, sval-Leuciscus
      svallizi, gray mullet-Mugil cephalus, and eel-Anguilla anguilla) taken out from
      the end fIow (last 20 km) of the river Neretva, south Croatia, in the wider
      region of town Metkovic, during the summer of the year 2003. Only Cd
      concentration in all fish types was higher than the maximal allowed concentration
      (MAC) in Croatia, but its concentration in muscles reaches this value only in
      four samples. However, in carp, tench, and mullet, Cd concentrations higher than
      MAC in some other countries were found. Hg concentration is much lower than MAC
      in the most countries. Pb is found in higher quantities only in carp, some values
      reaching MAC in Germany, and many values being higher than MAC in Denmark (with
      exception of gonads). As concentrations are much lower than MAC in all countries,
      but it seems that mullet tends to accumulate this metalloid, especially in the
      muscles. Therefore, in several samples, muscle As concentration in mullet reached
      half of the MAC value in the most countries. Of the analyzed fish types, eel,
      containing the smallest quantities of heavy metals, is recommended for human
      diet, while carp, consumed most frequently by local inhabitants and numerous
      tourists, shares with mullet the last place on the recommendation list. Also, it
      is suggested that meals prepared with analyzed fish sorts should not contain some
      inner organs (kidneys and liver), as well as gills (alternatively, the whole
      head). Our final conclusion is that fish types eating predominantly meat contain
      less heavy metal in their tissues, and therefore are more suitable for human
      diet.

PMID- 16453064
TI  - The nucleosome: a transparent, slippery, sticky and yet stable DNA-protein
      complex.
AB  - Roughly three quarters of eucaryotic DNA are tightly wrapped onto protein
      cylinders organized in so-called nucleosomes. Despite this fact, the wrapped DNA
      cannot be inert since DNA is at the heart of many crucial life processes. We
      focus here on physical mechanisms that might allow nucleosomes to perform a great
      deal of such processes, specifically 1) on unwrapping fluctuations that give DNA
      binding proteins access to the wrapped DNA portions without disrupting the
      nucleosome as a whole, 2) on corkscrew sliding along DNA and some implications
      and on 3) tail-bridging-induced attraction between nucleosomes as a means of
      controlling higher-order folding.

PMID- 16453066
TI  - Geographical clustering of pancreatic cancers in the Northeast Nile Delta region
      of Egypt.
AB  - The northeast Nile Delta, Egypt's most polluted region, appears to have a high
      incidence of pancreatic cancer. We sought to determine whether there is any
      geographic clustering of pancreatic cancers there and, if so, whether such
      clustering might be associated with environmental pollution. Using data from the
      medical records of the Gastrointestinal Surgical Center of Mansoura University in
      the Dakahleia Province of Egypt and detailed geographical maps of the northeast
      Nile Delta region, we plotted the residences of all 373 patients who had
      pancreatic cancer diagnosed between 1995 and 2000. The study region has 15
      administrative districts, whose centroid coordinates, population, and number of
      pancreatic cancer patients were determined for this study. Monte Carlo simulation
      identified statistically significant clustering of pancreatic cancer in five
      subdivisions located near the Nile River and Delta plains. This clustering was
      independent of population size and formed two larger clusters. When data were
      analyzed by sex, clustering of pancreatic cancer was observed in the same five
      subdivisions for men but only two subdivisions showed clustering for women.
      Together, our data suggest that there is clustering of pancreatic cancer cases in
      the northeast Nile delta region and that this clustering may be related to water
      pollution. Our data also warrant future studies of the association between water
      pollution and pancreatic cancer in the region.

PMID- 16453067
TI  - The potential for chromium to affect the fertilization process of Chinook salmon
      (Oncorhynchus tshawytscha) in the Hanford reach of the Columbia River,
      Washington, USA.
AB  - The Hanford Nuclear Reservation in south central Washington was claimed by the
      federal government as a site for the production of plutonium. During the course
      of production and operation of the facilities at Hanford, radionuclides and
      chromium were discharged directly into the river and also contaminated the
      groundwater. This study was designed to assess the effects of chromium (Cr) on
      Chinook salmon (Oncorhynchus tshawytscha) fertilization under exposure conditions
      similar to those of the Hanford Reach of the Columbia River. Chinook salmon
      gametes were exposed to aqueous Cr concentrations ranging from 0 to 266 microg Cr
      l(-1). The current ambient water-quality criteria (AWQC) established for the
      protection of aquatic life (United States Environmental Protection Agency [USEPA]
      1986) is 11 microg Cr l(-1). Cr has been measured in pore water from bottom
      sediments of the Columbia River at concentrations >600 microg Cr l(-1). Under
      exposure conditions designed to closely mimic events that occur in the river, the
      fertilization of Chinook salmon eggs was not affected by concentrations of Cr
      ranging from 11 to 266 microg Cr l(-1). Data suggest that the instantaneous
      nature of fertilization likely limits the potential effects of Cr on
      fertilization success. As a result, the current AWQC of 11 mug Cr l(-1) is most
      likely protective of Chinook salmon fertilization.

PMID- 16453069
TI  - Non-algorithmic access to calendar information in a calendar calculator with
      autism.
AB  - The possible use of a calendar algorithm was assessed in DBC, an autistic
      "savant" of normal measured intelligence. Testing of all the dates in a year
      revealed a random distribution of errors. Re-testing DBC on the same dates one
      year later shows that his errors were not stable across time. Finally, DBC was
      able to answer "reversed" questions that cannot be solved by a classical
      algorithm. These findings favor a non-algorithmic retrieval of calendar
      information. It is proposed that multidirectional, non-hierarchical retrieval of
      information, and solving problems in a non-algorithmic way, are involved in
      savant performances. The possible role of a functional rededication of low-level
      perceptual systems to the processing of symbolic information in savants is
      discussed.

PMID- 16453068
TI  - Predictors of positive psychosocial functioning of older adults in residential
      care facilities.
AB  - This research examined the contributions of active and passive coping for health
      problems, and meaning-based coping, to positive psychosocial functioning in a
      sample of 100 individuals in residential care with a mean age of 83.11 years old.
      Study participants resided in skilled care, intermediate care, or assisted living
      facilities. Based on interview data collected on site in participants'
      residential settings, hierarchical multiple regression analyses revealed that
      active and passive coping and meaning-based coping had separate influences on
      measures of positive psychosocial functioning. Active coping was correlated with
      higher positive affect, whereas passive coping was associated with higher
      negative affect and self-acceptance. Positive reappraisal, a meaning-based coping
      strategy, was uniquely associated with higher positive affect, positive social
      relations, and self-acceptance. Positive religious coping was not independently
      associated with positive psychosocial functioning indices, whereas negative
      religious coping was related to higher negative affect. Health functioning did
      not contribute to positive psychosocial functioning in this sample. The results
      confirm the separate importance of health-related and meaning-based coping
      strategies in explaining positive psychosocial functioning in older adults living
      in residential care settings.

PMID- 16453070
TI  - Subjective perceptual distortions and visual dysfunction in children with autism.
AB  - Case reports and sensory inventories suggest that autism involves sensory
      processing anomalies. Behavioral tests indicate impaired motion and normal form
      perception in autism. The present study used first-person accounts to investigate
      perceptual anomalies and related subjective to psychophysical measures. Nine high
      functioning children with autism and nine typically-developing children were
      given a questionnaire to assess the frequency of sensory anomalies, as well as
      psychophysical tests of visual perception. Results indicated that children with
      autism experience increased perceptual anomalies, deficits in trajectory
      discrimination consistent with dysfunction in the cortical dorsal pathway or in
      cerebellar midsagittal vermis, and high spatial frequency contrast impairments
      consistent with dysfunctional parvocellular processing. Subjective visual
      hypersensitivity was significantly related to greater deficits across vision
      tests.

PMID- 16453071
TI  - Enhanced perceptual functioning in autism: an update, and eight principles of
      autistic perception.
AB  - We propose an "Enhanced Perceptual Functioning" model encompassing the main
      differences between autistic and non-autistic social and non-social perceptual
      processing: locally oriented visual and auditory perception, enhanced low-level
      discrimination, use of a more posterior network in "complex" visual tasks,
      enhanced perception of first order static stimuli, diminished perception of
      complex movement, autonomy of low-level information processing toward higher
      order operations, and differential relation between perception and general
      intelligence. Increased perceptual expertise may be implicated in the choice of
      special ability in savant autistics, and in the variability of apparent
      presentations within PDD (autism with and without typical speech, Asperger
      syndrome) in non-savant autistics. The overfunctioning of brain regions typically
      involved in primary perceptual functions may explain the autistic perceptual
      endophenotype.

PMID- 16453072
TI  - Laparoscopic ventral hernia repair: a single center experience.
AB  - A retrospective chart review at the Carolinas Medical Center was performed on all
      patients who underwent laparoscopic ventral hernia repair (LVHR) from July 1998
      through December 2003. LVHR was successfully completed in 270 of the 277
      patients, or 98%, in whom it was attempted. Half of the patients (138/277) had at
      least one previous failed repair. The average defect measured 143.3 cm(2), and
      mesh was used in all repairs. The mean operating time was 168.3 min, mean blood
      loss was 50 cc, and average length of hospitalization was 3.0 days. Thirty-four
      complications occurred in 31 patients (11%). Only two mesh infections occurred
      (0.7%). At a mean follow-up period of 21 months, the rate of hernia recurrence
      was 4.7%. As experience grows and length of follow-up expands, LVHR may become
      the preferred approach for ventral hernia in difficult patients, especially obese
      patients and patients who have failed prior open repairs.

PMID- 16453073
TI  - Treatment of large incisional abdominal wall hernias, using a modified
      preperitoneal prosthetic mesh repair.
AB  - Very large and complex incisional hernias, especially those with loss of
      abdominal wall, can be a very interesting and perplexing problem, which present a
      particular challenge to the surgeon. The reported technique was developed and
      refined by one of our surgeons, between 1998 and 1999 for the repair of
      incisional hernias in a selected group of patients with large defects, often with
      a major loss of abdominal wall, overweight and previous attempts for incisional
      hernia repair. The technique involves a modified preperitoneal approach and was
      used on 43 eligible patients between 1999 and 2002. There were 30 females and 13
      males at a mean age of 61 years. The median ASA score of the group was 2, with a
      mean BMI of 30.4 and a mean hernia surface area of 162 cm(2). One-third of the
      patients had one or more previous incisional hernia repair. Mean operating time
      was 190 min with an average hospital stay of 5.7 days. Postoperative
      complications occurred in 28% of the patients, most of which were minor and did
      not necessitate admission to the intensive care unit. None of the patients died.
      Wound infections occurred in 9.3%, was associated with an increased risk for
      cutaneous sinus formation, but not for mesh removal or hernia recurrence. A
      recurrence rate of 12.5% was found after a mean follow-up period of 46 months. We
      advocate this procedure for the repair of large, complex incisional hernias with
      loss of abdominal domain in patients with significant risk factors for
      recurrence.

PMID- 16453074
TI  - Recurrent paraesophageal hernia due to diaphragm rupture: a case report.
AB  - A 58-year-old male patient was operated for complaints of dysphagia, anemia and
      retrosternal discomfort due to a type II hiatal hernia. A complete hernia sac
      excision and posterior crural repair was performed laparoscopically with support
      of the da Vincitrade mark robotic system. An antireflux procedure was not
      performed because of the absence of gastroesophageal reflux disease. Nine months
      after surgery the patient presented with recurrent complaints of dysphagia and
      retrosternal pain. Barium esophagram series revealed a recurrent paraesophageal
      hernia which was confirmed on esophagogastroscopy. A robot-assisted re
      laparoscopy was performed. Left to the still intact hiatoplasty of the original
      operation a tear in the diaphragm, through which part of the stomach covered with
      peritoneum had herniated, was encountered. The hernia sac was excised, the
      diaphragmatic defect closed and reinforced with an expanded
      polytetrafluoroethylene strip of 5 x 8 cm. After surgery the patient recovered
      quickly, oral intake was resumed on the first postoperative day and the hospital
      stay was 3 days. The use of prosthetic mesh to reinforce the hiatoplasty and the
      addition of an antireflux procedure after hiatal hernia repair are ongoing
      controversial aspects of hiatal hernia repair. Reports on laparoscopic redo
      surgery for recurrent diaphragmatic hernia are limited and will be addressed in
      this case report, in perspective of the aforementioned controversial components.

PMID- 16453075
TI  - Laparoscopic incisional hernia repair: a review of the literature.
AB  - Incisional hernia is a common long-term complication of abdominal surgery.
      Historically the open repair with or without mesh was the mainstay of treatment.
      However, many recently published laparoscopic repair studies have challenged
      surgeons to re-evaluate which technique provides the best short and long-term
      outcomes. A Medline search of all English-language literature was performed using
      the keywords 'incisional', 'ventral', 'hernia', 'laparoscopic', and 'open'.
      Further references were obtained by cross-referencing the bibliography in each
      paper. Current evidence suggests that the laparoscopic incisional hernia repair
      is the optimal surgical treatment. A laparoscopic repair appears to shorten
      hospital stay, decrease perioperative complication rates, and decrease recurrence
      rates. However, there is no randomized trial utilizing a standardized
      complication grading system making it difficult to draw a definitive conclusion
      as to which repair is best.

PMID- 16453076
TI  - Predictive factors comparison of complications and recurrences in three tension
      free herniorraphy techniques.
AB  - Inguinal herniorraphy is one of the most common surgeries performed. Avoiding
      hernia recurrence is a primary concern. Hence, it is necessary to analyze the
      predictive factors of postoperative complications and recurrence. To compare the
      predictive factors of postoperative complications and recurrences of hernias
      among three tension-free open herniorraphy techniques. Five hundred and fifty-one
      inguinal hernia patients, operated on with one of three tension-free anterior
      approach herniorraphy techniques, were included in a cohort study. The three
      techniques were: Lichtenstein (n=214), Mesh-Plug (n=201) and Prolene Hernia
      System (PHS, n=136). The patients were evaluated at 15 days, 1 month, 6 months
      and then every year up to 5 years after hernioplasty. The variables evaluated
      were recurrences and postoperative complications. Relative risk was estimated
      from a univariate analysis of the presumable risk values, after which a
      multivariate analysis was carried out. Complications [n=27, (4.9%)] were more
      frequently associated with incarcerated hernia, a coexisting disease at the time
      of operation, hospitalization longer than 1 day, previous herniorraphy, a
      herniary ring larger than 4.5 cm and a history of postoperative complications.
      Recurrence was greater for the Mesh-Plug group [n=5 (2.5%), RR: 4.35 (CI: 0.85
      22.23)] than for the Lichtenstein [n=2 (0.9%), RR: 0.63 (0.06-3.87)] and PHS [n=0
      (0%), RR de 0 (0-2.39)] groups. The presence of coexisting disease during
      hernioplasty, incarcerated hernia and an extended hospital stay are predictive
      factors for hernia complications. Previous herniorraphy, a herniary ring larger
      than 4.5 cm and postoperative complications are predictive factors for hernia
      recurrence.

PMID- 16453077
TI  - In vitro infectability of prosthetic mesh by methicillin-resistant Staphylococcus
      aureus.
AB  - Although mesh use is important for effective herniorrhaphy in adults, prosthetic
      infections can cause serious morbidity. Bacterial adherence to the mesh is a
      known precursor to prosthetic infection. We compared the ability of common mesh
      prosthetics to resist bacterial adherence. The meshes studied included
      polypropylene (Marlex, expanded polytetrafluoroethylene (PTFE) with and without
      silver chlorhexidine coating (DualMesh Plus and Dualmesh) composite meshes
      (Composix E/X, Proceed, and Parietex Composite) and lightweight polypropylene
      meshes (TiMesh, Ultrapro, and Vypro). Fifteen samples of each mesh type were
      individually inoculated with a suspension of 10(8 )methicillin-resistant
      Staphylococcus aureus (MRSA) in tryptic soy broth. After incubation at 37 degrees
      C for 1 h, the mesh pieces were then removed and serially washed. The colony
      forming units (CFU) of MRSA present in the initial inoculum, at the end of the 1
      h warm-water bath (broth count), and the pooled washes (wash count), were
      determined using serial dilutions and spot plating. The bacteria not accounted
      for in the broth or wash counts were considered adhered to the mesh. Samples of
      each mesh type were also analyzed using scanning electron microscopy (SEM). Data
      are presented as the mean percentage adherence with ANOVA and Tukey's test used
      to determine significance (P<0.05). The DualMesh Plus mesh had no detectable MRSA
      in the broth or the pooled wash samples. Dualmesh had less adherence compared
      with Marlex, Proceed, and Vypro (P<0.05). Conversely, Vypro had a statistically
      higher adherence (96%, P<0.05) as compared to TiMesh, Ultrapro, Composix E/X, and
      Parietex Composite. SEM confirmed bacterial adherence to all the mesh types
      except DualMesh Plus. The ability of a biomaterial to resist infection has an
      important clinical significance. DualMesh Plus, due to its antimicrobial coating,
      is the only mesh type of the nine tested that demonstrated a bactericidal
      property. Standard PTFE (Dualmesh) also had less bacterial adherence. Vypro
      demonstrated an increase in bacterial adherence; this was possibly due to the
      multifilament polyglactin 910 weaved within the prolene component of the mesh.

PMID- 16453079
TI  - Acute arthritis of carpal bones secondary to metastatic gastric cancer.
AB  - A 39-year-old woman presented with acute onset of arthralgia in both wrists.
      Although her primary gastric cancer was in remission after previous treatment,
      carcinomatous arthritis was suggested by the osteolytic radiographic findings and
      refractoriness to nonsteroidal anti-inflammatory drugs, which was then confirmed
      by synovial fluid cytopathology. In view of the high incidence of gastric cancer
      in Korea, gastric cancer involving the carpal bones should be considered when we
      encounter a patient presenting with inflammatory peripheral joint arthritis,
      which might be the first sign of recurrence.

PMID- 16453080
TI  - A brief history of medical taxonomy and diagnosis.

PMID- 16453081
TI  - Mental health problems in early adolescents in the Netherlands: differences
      between school and household surveys.
AB  - OBJECTIVE: A large representative sample of early adolescents in the Netherlands
      was investigated to assess mental health problems in a school survey. These
      results were compared to results from former household surveys. In addition,
      several socio-demographic determinants were analysed. METHOD: A random sample of
      schools in the Netherlands was approached for participation in the Health
      Behaviour in School-aged Children Survey study (response rate at school level,
      60% in primary education and 45% in secondary education). Within schools, a
      random selection of classes from the schools participated in the study (response
      rate within schools >95%). We analysed the percentage of children scoring in the
      problem range on each of the syndromes of the Youth Self Report and compared
      these to the percentages found in a former population study. The impact of
      several socio-demographic background variables was assessed. RESULTS:
      Approximately 20% of the boys and 23% of the girls have total problem scores in
      the problem range. These percentages are much higher than those found in
      population studies in the Netherlands so far, particularly in girls. In
      multivariate analyses, gender, socio-economic status and family composition were
      found to be of influence. Migrant status does not appear to be of importance once
      other background variables are taken into account. CONCLUSIONS: In school surveys
      on mental health problems, higher problem rates may be found than in population
      surveys conducted in household settings. This effect has seldom been discussed.
      It is suggested that this survey context has to be taken into account more
      explicitly when comparing results of surveys.

PMID- 16453082
TI  - Yellow leaf of sugarcane is caused by at least three different genotypes of
      sugarcane yellow leaf virus, one of which predominates on the Island of Reunion.
AB  - The genetic diversity of sugarcane yellow leaf virus (SCYLV) was analyzed with 43
      virus isolates from Reunion Island and 17 isolates from world-wide locations. We
      attempted to amplify by reverse-transcription polymerase chain reaction (RT-PCR),
      clone, and sequence four different fragments covering 72% of the genome of these
      virus isolates. The number of amplified isolates and useful sequence information
      varied according to each fragment, whereas an amplicon was obtained with
      diagnostic primers for 59 out of 60 isolates (98%). Phylogenetic analyses of the
      sequences determined here and additional sequences of 11 other SCYLV isolates
      available from GenBank showed that SCYLV isolates were distributed in different
      phylogenetic groups or belonged to single genotypes. The majority of isolates
      from Reunion Island were grouped in phylogenetic clusters that did not contain
      any isolates from other origins. The complete six ORFs (5612 bp) of five SCYLV
      isolates (two from Reunion Island, one from Brazil, one from China, and one from
      Peru) were amplified, cloned, and sequenced. The existence of at least three
      distinct genotypes of SCYLV was shown by phylogenetic analysis of the sequences
      of these isolates and additional published sequences of three SCYLV isolates
      (GenBank accessions). The biological significance of these genotypes and of the
      origin of the distinct lineage of SCYLV in Reunion Island remains to be
      determined.

PMID- 16453083
TI  - Insights into structural proteins of 936-type virulent lactococcal
      bacteriophages.
AB  - bIL41 and bIL170, virulent phages of Lactococcus lactis belonging to the 936
      group, possess a late gene named l12, coding a putative fiber sharing partial
      similarity to diverse gene products of dairy phages, including host-range
      determinants, but whose function is unknown in this group. We observed that the
      full-size gpl12 gene product is a minor protein constitutive of both phage
      particles. A derivative of bIL41 deleted for part of this gene was constructed by
      homologous recombination. The recombinant bIL41DeltaL12 showed normal propagation
      on strain IL1403 and no altered head and tail structures, demonstrating its non
      essential role under our laboratory conditions. bIL170 was investigated for major
      structural components. Tails were characterized by electron microscopy and image
      analysis, which indicated that the major repeat unit of the tail occupied a
      maximum volume of 18.5 nm3, corresponding to a size of 20 kDa for a globular
      protein. Total protein profiles and head-enriched fractions of bIL170 exhibited a
      major 38 kDa protein, identified by N-terminal sequence as the product of l13.
      This result questions some of the functional predictions deduced from synteny
      relationships assumed for the lambda-supergroup of the family Siphoviridae to
      which the 936-type phages were proposed to belong.

PMID- 16453084
TI  - Novel reverse transcription loop-mediated isothermal amplification for rapid
      detection of foot-and-mouth disease virus.
AB  - Speed is paramount in the diagnosis of foot-and-mouth disease (FMD) and
      simplicity is required if a test is to be deployed in the field. The development
      of a one-step, reverse transcription loop-mediated amplification (RT-LAMP) assay
      enables FMD virus (FMDV) to be detected in under an hour in a single tube without
      thermal cycling. A fragment of the 3D RNA polymerase gene of the virus is
      amplified at 65 degrees C in the presence of a primer mixture and both reverse
      transcriptase and Bst DNA polymerase. Compared with real-time RT-PCR, RT-LAMP was
      consistently faster, and ten copies of FMDV transcript were detected in twenty
      two minutes. Amplification products were detected by visual inspection, agarose
      gel electrophoresis, or in real-time by the addition of a fluorescent dye. The
      specificity of the reaction was demonstrated by the absence of amplification of
      RNA from other viruses that cause vesicular diseases and from that of genetically
      related picornaviruses. Diagnostic sensitivity was validated by the amplification
      of reference FMDV strains and archival material from field cases of FMD. In
      comparison with the performance of the established diagnostic TaqMan assay, RT
      LAMP appears to be sensitive, rapid, specific, and cost-effective, with the
      potential for field deployment and use by developing countries for FMDV
      surveillance.

PMID- 16453085
TI  - A short history of neurosciences in Austria.
AB  - Based on internal medicine and psychiatry and in close connection with pathology,
      the neurosciences in Austria began to develop in the 18(th) century, e.g. with
      the description of inflammation of the central nervous system by J. P. Franck
      (1745-1823) and the "phrenology" by F. J. Gall (1745-1823). Under the influence
      of the great pathologist C. Rokitansky (1804-1878), the tripode of the Vienna
      neurology - L. Turck (1810-1868), as initiator, Th. v. Meynert (1833-1892) the
      activator, and H. Obersteiner (1847-1922) as the founder of the Vienna
      Neurological Institute, presented basic contributions to the morphology and
      pathology of the nervous system. At the end of the 19(th) and in the early 20(th)
      century, they were followed by important publications by S. Fred (aphasia), C.
      Redlich (tabes dorsalis), F. Straussler (CNS syphilis), A. Spitzer (fiber anatomy
      of the brain), P. Schilder (diffuse sclerosis), R. Barany (Nobel price for
      physiology and medicine 1914), J. Wagner v. Jauregg (Nobel price for medicine,
      1927), O. Loewi (Nobel Price for Physiology and Medicine together with Sir H.
      Dale, 1936), A. Schuller (histiocytosis X), C. v. Economo (encephalitis
      lethargica and cytoarchitectonics of the human cerebral cortex), E. Pollak
      (Wilson disease), E. Gamper (mesencephalic subject), J. Gerstmann (Gerstmann
      Straussler-Scheinker syndrome and Gerstmann parietal syndrome), H. Hoff with L.
      Schonbauer (brain tumors and surgery), and others. Major research institutions
      were the departments of psychiatry I and II at the University of Vienna School of
      Medicine (foundation 1870), unification 1911, separation into departments of
      neurology, psychiatry and neuropsychiatry of children and adolescents in 1971),
      the Obersteiner Institute in Vienna (foundation 1882, separation 1993), the
      university departments at Graz and Innsbruck, both founded in 1891, and other
      laboratories, where renouned clinicans and neuroscientists, like O. Marburg, H.
      Hoff, O. Potzl, O. Kauders, F. Seitelberger, H. Tschabitscher, K. Weingarten, H.
      Reisner,W. Birkmayer, H. Petsche, F. Gerstenbrand, H. Bernheimer, H. W. Heiss, H.
      Lassmann, W. Poewe, L. Deecke, and many of their associates produced important
      contributions to wide areas of modern neurosciences. Important for the future are
      the foundation of the Institute of Brain Research at Vienna Medical University
      and of the Austrian Society of Neurology which will give further impact for the
      future progress of neuroscience research in Austria and its integration into the
      international science community.

PMID- 16453086
TI  - Statin-related muscle complaints: an underestimated risk.

PMID- 16453087
TI  - Ca2+-sensitisers--a promising option to treat heart failure?
AB  - Because the number of transplants is still fewer than the number of patients
      waiting for a donor organ, new concepts of therapy are needed that allow patients
      to bridge the time gap until heart transplantation or even to improve symptoms
      while on treatment. Ca(2+)-sensitisers are agents that directly influence
      myofilaments and/or the cross-bridge-cycle. Depending on the molecular mechanisms
      underlying their action, Ca(2+)-sensitisers have been divided into three classes.
      While, a number of Ca(2+)-sensitising drugs have been described, currently only
      the Ca(2+)-sensitisers pimobendan and levosimendan are in clinical use. This
      review provides a survey on the molecular mechanisms and the therapeutic
      effectiveness of Ca(2+)-sensitisers for the treatment of human heart failure.

PMID- 16453088
TI  - Multidisciplinary vascular screening program modestly improves the medical
      treatment of vascular risk factors.
AB  - PURPOSE: This study investigated whether recommendations given to the treating
      vascular specialist and the GP by a multidisciplinary team of vascular
      specialists concerning the medical treatment of risk factors, based on
      international guidelines, led to an increased medication use in a high-risk
      population. METHODS: Data were obtained from 618 patients enrolled in the SMART
      study, an ongoing single-center prospective cohort study of patients referred to
      the University Medical Center Utrecht for atherosclerotic vascular diseases. All
      patients underwent a vascular screening and their physicians received
      recommendations concerning the medical treatment of newly detected or not yet
      sufficiently treated vascular risk factors. After a median follow-up of 29
      months, questionnaires about medication use were sent to 618 patients; 534 (86%)
      questionnaires were returned. Actual use of medication was compared with medical
      treatment recommendation given at baseline. RESULTS: The proportion of patients
      on antihypertensive medication with hypertension (> or =140/90 mmHg) and not
      diagnosed with coronary heart disease increased from 56% to 68% (95% confidence
      interval (95% CI) 2 - 23). The frequency of lipid-lowering medication use
      increased substantially from 47% to 69% (95% CI 17 - 28). The frequency of
      glucose-lowering medication use increased slightly from 11% to 14% (95% CI 1 -
      7). The use of folic acid increased from 2% to 14% (95% CI 9 - 15) in patients
      with hyperhomocysteinaemia. CONCLUSIONS: Medical treatment recommendations,
      formulated by a multidisciplinary team, led to a significant increase in
      medication use. The increase is marginal compared with trends in medication use
      without this intervention in usual care.

PMID- 16453089
TI  - Effects of long-term treatment with candesartan on hemodynamics and organ damage
      in spontaneously hypertensive rats.
AB  - This study was designed to investigate the effects of candesartan on blood
      pressure (BP) and blood pressure variability (BPV) reductions, baroreflex
      sensitivity (BRS) amelioration, and organ protection in spontaneously
      hypertensive rats (SHR). METHODS: Studies were performed in two groups of SHR (n
      = 13 for control rats; and n = 20 for candesartan-treated rats) and one group of
      WKY rats (n = 13). Candesartan (3 mg /kg/d) was given in rat chow for 4 months.
      BP was then continuously recorded for 24 hours in conscious state. After the
      determination of BRS, rats were killed for organ-damage evaluation. RESULTS: Long
      term treatment with candesartan significantly reduced BP and BPV expressed by
      both standard deviation and variation coefficient of BP, enhanced BRS and
      produced obvious organ protection. Compared with BP level, BPV and BRS values
      showed a closer or similar relationship with organ-damage parameters in SHR.
      Multiple regression analysis showed that the decrease in left ventricular
      hypertrophy was most closely associated with the increase in BRS, whereas the
      decrease in aortic hypertrophy was most closely associated with the decrease in
      24-hour systolic BPV, and the amelioration in renal lesions, with the increase in
      BRS and the decrease in 24-hour systolic BPV. CONCLUSION: long-term treatment
      with candesartan results in organ protection in SHR. Besides BP reduction, the
      decrease in BPV and the restoration of BRS are significantly related to this
      organ protection.

PMID- 16453090
TI  - Mild to moderate muscular symptoms with high-dosage statin therapy in
      hyperlipidemic patients--the PRIMO study.
AB  - OBJECTIVES: To characterize the risk factors, rate of occurrence, onset, nature
      and impact of mild to moderate muscular symptoms with high-dosage HMG-CoA
      reductase inhibitor (statin) therapy in general practice. METHODS: The Prediction
      du Risque Musculaire en Observationnel (Prediction of Muscular Risk in
      Observational conditions, PRIMO) survey was an observational study of muscular
      symptoms in an unselected population of 7924 hyperlipidemic patients receiving
      high-dosage statin therapy in a usual care, outpatient setting in France.
      Information on patient demographics, treatment history and muscular symptoms was
      obtained by questionnaires. RESULTS: Multivariate analysis revealed the strongest
      predictors for muscular symptoms to be a personal history of muscle pain during
      lipid-lowering therapy (odds ratio, OR, 10.12, 95% CI 8.23-12.45; P < 0.0001),
      unexplained cramps (OR 4.14; 95% CI 3.46-4.95; P < 0.0001) and a history of
      creatine kinase (CK) elevation (OR 2.04; 95% CI 1.55-2.68; P < 0.0001). Overall,
      muscular symptoms were reported by 832 patients (10.5%), with a median time of
      onset of 1 month following initiation of statin therapy. Muscular pain prevented
      even moderate exertion during everyday activities in 315 patients (38%), while 31
      (4%) were confined to bed or unable to work. Fluvastatin XL was associated with
      the lowest rate of muscular symptoms (5.1%) among individual statins. CONCLUSION:
      PRIMO demonstrated that mild to moderate muscular symptoms with high-dosage
      statin therapy may be more common and exert a greater impact on everyday lives
      than previously thought. Knowledge of the risk factors for muscular symptoms will
      allow identification and improved management of high-risk patients. The risk of
      muscular symptoms with fluvastatin XL treatment may be lower than with high
      dosages of other statins.

PMID- 16453091
TI  - Strategies for modifying high-density lipoprotein cholesterol: a role for
      nicotinic acid.
AB  - Statin-mediated lowering of low-density lipoprotein cholesterol (LDL-C) is
      regarded as the foundation of lipid-modifying therapy. However, the residual
      cardiovascular risk for statin-treated patients remains high, indicating the need
      for therapeutic intervention against other lipid targets as well as non-lipid
      risk factors. Low levels of high-density lipoprotein cholesterol (HDL-C) are
      established as a strong independent risk factor for cardiovascular disease.
      Intervention studies have also demonstrated clinical benefits associated with HDL
      C raising. Although lifestyle modification does play an important role in raising
      HDL-C, most patients with a low HDL-C and at high risk of coronary events also
      require pharmacological treatment to achieve the target. Of the available
      treatment options, nicotinic acid is the most potent agent for raising HDL-C (by
      26% at clinically recommended doses), while substantially lowering triglycerides
      and LDL-C. The addition of nicotinic acid to primary statin therapy is a logical
      approach to dyslipidaemia management, given their complementary mechanism of
      action, and is supported by recent clinical trials such as the Arterial Biology
      for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER)
      2 study. Raising HDL-C will increasingly become an important secondary focus of
      dyslipidaemia management.

PMID- 16453092
TI  - [Lipid lowering after percutaneous coronary intervention. Intended and achieved
      treatment goals in real life].
AB  - BACKGROUND: Dyslipidemia is associated with development and progression of
      coronary artery disease. Especially patients after coronary revascularization
      benefit by treatment with lipid-lowering drugs. Guidelines for lipid-lowering
      therapy in patients with or without coronary artery disease recommend treatment
      goals of lipid levels. However, relevant discrepancies between evidence-based
      goals and achieved lipid levels in "real life" are reported in large studies.
      METHODS AND RESULTS: In this study the dynamics of lipid levels (total
      cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) and of lipid
      lowering drugs were analyzed over a 5.5-month period in patients undergoing
      percutaneous coronary intervention. At the time of coronary intervention only
      49.8% of patients were on lipid-lowering drugs, during follow-up dosage was
      modified only in exceptional cases. Although 87.5% of patients were treated at
      the time of follow-up, guideline-oriented lipid levels were achieved only in
      32.5% of patients after 5.5 months. CONCLUSION: In a high-risk patient population
      after coronary revascularization, an ineffective treatment of
      hypercholesterolemia was found. A major problem is the lack of dosage
      modification of lipid-lowering drugs after initiation. By closer cooperation
      between hospital and general practitioner lipid-lowering treatment will be
      optimized and the rate of cardiovascular events will be decreased over long-term
      follow-up.

PMID- 16453093
TI  - [EGFR/HER1 inhibition: an example of new targeted therapies in non-small cell
      lung cancer].
AB  - BACKGROUND: Lung cancer is one of the most common forms of cancer in western
      industrialized countries. Patients with advanced non-small cell lung cancer
      (NSCLC) have a poor prognosis and suffer many tumor-associated symptoms.
      Unfortunately, approximately 70% of patients with NSCLC present themselves with
      advanced poor-prognosis stage III and IV disease. In advanced disease, treatment
      is palliative and symptom-oriented. New less Adenotoxic drugs are urgently
      needed. One of the targets of new agents is the human epidermal growth factor
      receptor (EGFR/HER1), and agents targeting this receptor include erlotinib,
      gefitinib and cetuximab. CLINICAL STUDIES: Erlotinib, gefitinib and cetuximab
      have been investigated in different clinical studies and provided objective
      responses and symptom relief. A benefit in survival could only be observed in
      second- and third-line therapy with erlotinib. All new agents have been generally
      well tolerated. Erlotinib was recently approved in the USA and Europe for second-
      and third-line treatment of patients with locally advanced or metastatic NSCLC.
      CONCLUSION: Anti-EGFR has shown promising antitumor activity in NSCLC with a mild
      toxicity profile. However, some clinical issues such as screening for potentially
      responsive patients and optimal combination with other drugs should be the aim of
      future studies.

PMID- 16453094
TI  - [Stress, hormones, and neuronal signals in the pathophysiology of rheumatoid
      arthritis. The negative impact on chronic inflammation].
AB  - This review demonstrates that hormonal and neuronal factors, which are released
      during stressful situations, can unfavorably influence the two chronic diseases
      of rheumatoid arthritis and juvenile idiopathic arthritis. Noradrenaline and
      cortisol are in the focus of this review. In the said two chronic inflammatory
      diseases, it is obvious that apart from the immune system also the endocrine and
      nervous system play an essential role in the stress-induced initiation and
      aggravation of these diseases.

PMID- 16453095
TI  - [Antihypertensive drug utilization in obese patients].
AB  - BACKGROUND AND PURPOSE: Obesity and arterial hypertension are epidemic and often
      seen in combination. In spite of the frequency and the difficulties in treating
      these patients to goal, there are no recent data on the prescription of
      antihypertensive drugs in primary care in this patient population. MATERIAL AND
      METHODS: Therefore, the data of a nationwide observational study from 2004 were
      evaluated in which more than 70,000 patients with arterial hypertension were
      investigated. It was documented, which antihypertensive classes are preferred in
      obese patients, which are the most often used substances and how these are dosed.
      RESULTS: (1) Antihypertensive pharmacotherapy of obese patients is differentiated
      in terms of substances used, but less in terms of dosage. (2) Combinations of
      drugs are more often used to control the blood pressure of these patients and ACE
      inhibitors and diuretics are most often preferred. CONCLUSION: These results show
      that the availability of a number of effective antihypertensive drugs is not
      sufficient to secure an adequate control of blood pressure. The timely
      combination of antihypertensive drugs in reduced dose (alpha-blockers, beta
      blockers, diuretics, and calcium antagonists) in combination with high doses of
      agents blocking the renin-angiotensin system (RAS) could improve the efficacy
      while reducing side effects.

PMID- 16453096
TI  - [New CT procedures in cardiovascular diagnosis].

PMID- 16453097
TI  - [Off-label use in long-term anticoagulation after liver transplantation due to
      phenprocoumon-induced hepatic failure].
AB  - BACKGROUND: Drug therapy should be individualized according to criteria of
      efficacy, adverse effects, and treatment adherence. This is particularly
      important at the interface of inpatient and ambulatory care. Aspects of drug
      approval (labeling) and individual refunding by health care insurance should also
      be taken into account. CASE REPORT: A patient (male, 61 years, painter) showed
      elevated transaminases after treatment with phenprocoumon because of a deep vein
      thrombosis in 1999. Transaminases normalized completely after discontinuation of
      phenprocoumon. Other reasons for the elevated transaminases could be excluded.
      After a recurrent thrombosis in 2003 phenprocoumon was prescribed again followed
      by recurrent elevation of transaminases and subsequent cholestatic hepatitis
      progressing to fulminant hepatic failure that required liver transplantation.
      After transplantation the patient's general state of health was good and liver
      function nearly normal. Anticoagulation was indicated beyond the postoperative
      phase because of recurrent deep vein thrombosis and atrial fibrillation. A low
      molecular-weight heparin was chosen for long-term treatment. CONCLUSION: A low
      molecular-weight heparin appears to be the most appropriate way to maintain
      effective and safe anticoagulation in this patient. Coumarins carry a residual
      risk of an extrahepatic, immunologically mediated cross-sensitization. Long-term
      use of ximelagatran may also cause liver damage. For heparinoids, hirudins, and
      other drugs affecting coagulation like platelet aggregation inhibitors,
      therapeutic evidence is not sufficient. Though subcutaneous application of
      heparin is a disadvantage for the patient, therapeutic alternatives do not have
      better documented efficacy or less hepatotoxic potential. The low-molecular
      weight heparin fulfills the criteria for refunding set by federal jurisdiction.

PMID- 16453098
TI  - [DRG and coding: 2006 updates for pneumology].

PMID- 16453099
TI  - [From the molecular genetics of Alport's syndrome to principles of organo
      protection in chronic renal diseases].
AB  - BACKGROUND: Scarring is known to be the endpoint of most chronic kidney diseases.
      Therefore, prevention of renal fibrosis is a very important topic. The hereditary
      type IV collagen disease Alport's syndrome is a rare, but challenging cause of
      chronic renal fibrosis. PATHOGENESIS OF GLOMERULAR AND INTERSTITIAL RENAL
      FIBROSIS IN HUMANS: Increasing knowledge about the pathogenesis of Alport's
      syndrome may help to find principles of nephro-protection in chronic renal
      diseases. The defect gene in Alport's syndrome causes an altered assembly of
      extracellular matrix leading to a defect cell-matrix interaction and fibrosis.
      This scarring is regulated by comparable mechanisms as in diabetic nephropathy or
      chronic inflammatory renal diseases. NEPHRO-PROTECTION IN ANIMAL MODELS: By using
      an Alport animal model of chronic renal fibrosis, principles of nephro-protective
      therapies such as blockade of the renin-angiotensin system or the effect of HMG
      CoA reductase inhibitors can be investigated. CURRENT AND FUTURE NEPHRO
      PROTECTION IN HUMANS: The same model serves for evaluation of new organo
      protective therapies such as vasopeptidase inhibitors, blockade of endothelin,
      chemokine and collagen receptors as well as stem cell therapy and their potential
      benefit for patients with chronic renal diseases.

PMID- 16453100
TI  - [Congenital bicuspid aortic valve]].

PMID- 16453101
TI  - sll1981, an acetolactate synthase homologue of Synechocystis sp. PCC6803,
      functions as L-myo-inositol 1-phosphate synthase.
AB  - L-myo-inositol 1-phosphate synthase (EC 5.5.1.4; MIPS) catalyzes the first rate
      limiting conversion of D-glucose 6-phosphate to L-myo-inositol 1-phosphate in the
      inositol biosynthetic pathway. In an earlier communication we have reported two
      forms of MIPS in Synechocystis sp. PCC6803 (Chatterjee et al. in Planta 218:989
      998, 2004). One of the forms with an approximately 50 kDa subunit has been found
      to be coded by an as yet unassigned ORF, sll1722. In the present study we have
      purified the second isoform of MIPS as an approximately 65 kDa protein from the
      crude extract of Synechocystis sp. PCC6803 to apparent homogeneity and
      biochemically characterized. MALDI-TOF analysis of the 65 kDa protein led to its
      identification as acetolactate synthase large subunit (EC 2.2.1.6; ALS), the
      putatively assigned ORF sll1981 of Synechocystis sp. PCC6803. The PCR amplified
      approximately 1.6 kb product of sll1981 was found to functionally complement the
      yeast inositol auxotroph, FY250 and could be expressed as an immunoreactive
      approximately 65 kDa MIPS protein in the natural inositol auxotroph,
      Schizosaccharomyces pombe. In vitro MIPS activity and cross reactivity against
      MIPS antibody of purified recombinant sll1981 further consolidated its identity
      as the second probable MIPS gene in Synechocystis sp. PCC6803. Sequence
      comparison along with available crystal structure analysis of the yeast MIPS
      reveals conservation of several amino acids in sll1981 essential for substrate
      and co-factor binding. Comparison with other prokaryotic and eukaryotic MIPS
      sequences and phylogenetic analysis, however, revealed that like sll1722, sll1981
      is quite divergent from others. It is probable that sll1981 may code for a
      bifunctional enzyme protein having conserved domains for both MIPS and
      acetolactate synthase (ALS) activities.

PMID- 16453102
TI  - Novel characteristics of UDP-glucose dehydrogenase activities in maize: non
      involvement of alcohol dehydrogenases in cell wall polysaccharide biosynthesis.
AB  - UDP-glucose dehydrogenase (UDPGDH) activity was detected in extracts of maize
      cell-cultures and developing leaves. The reaction product was confirmed as UDP
      glucuronate. Leaf extracts from null mutants defective in one or both of the
      ethanol dehydrogenase genes, ADH1 and ADH2, had similar UDPGDH activities to wild
      type, showing that UDPGDH activity is not primarily due to ADH proteins. The
      mutants showed no defect in their wall matrix pentose:galactose ratios, or
      matrix:cellulose ratio, showing that ADHs were not required for normal wall
      biosynthesis. The majority of maize leaf UDPGDH activity had K (m) (for UDP
      glucose) 0.5-1.0 mM; there was also a minor activity with an unusually high K (m)
      of >50 mM. In extracts of cultured cells, kinetic data indicated at least three
      UDPGDHs, with K (m) values (for UDP-glucose) of roughly 0.027, 2.8 and >50 mM
      (designated enzymes E(L), E(M) and E(H) respectively). E(M) was the single major
      contributor to extractable UDPGDH activity when assayed at 0.6-9.0 mM UDP-Glc.
      Most studies, in other plant species, had reported only E(L)-like isoforms.
      Ethanol (100 mM) partially inhibited UDPGDH activity assayed at low, but not
      high, UDP-glucose concentrations, supporting the conclusion that at least E(H)
      activity is not due to ADH. At 30 microM UDP-glucose, 20-150 microM UDP-xylose
      inhibited UDPGDH activity, whereas 5-15 microM UDP-xylose promoted it. In
      conclusion, several very different UDPGDH isoenzymes contribute to UDP
      glucuronate and hence wall matrix biosynthesis in maize, but ADHs are not
      responsible for these activities.

PMID- 16453103
TI  - Benzene degradation coupled with chlorate reduction in a soil column study.
AB  - Perchlorate and chlorate are electron acceptors that during reduction result in
      the formation of molecular oxygen. The produced oxygen can be used for activation
      of anaerobic persistent pollutants, like benzene. In this study chlorate was
      tested as potential electron acceptor to stimulate benzene degradation in anoxic
      polluted soil column. A chlorate amended benzene polluted soil column was
      operated over a period of 500 days. Benzene was immediately degraded in the
      column after start up, and benzene removal recovered completely after omission of
      chlorate or a too high influent chlorate concentration (22 mM). Mass balance
      calculations showed that per mole of benzene five mole of chlorate were reduced.
      At the end of the experiment higher loading rates were applied to measure the
      maximal benzene degradation rate in this system; a breakthrough of benzene was
      not observed. The average benzene degradation rate over this period was 31
      micromol l(-1) h(-1) with a maximal of 78 micromol l(-1) h(-1). The high
      degradation rate and the necessity of chlorate indicate that oxygen produced
      during chlorate reduction indeed is used for the activation of benzene. This is
      the first column study where benzene biodegradation at a high rate coupled with
      anaerobic chlorate reduction is observed.

PMID- 16453104
TI  - A review of the contributions of Albert Einstein to earth sciences--in
      commemoration of the World Year of Physics.
AB  - The World Year of Physics (2005) is an international celebration to commemorate
      the 100th anniversary of Einstein's "Annus Mirabilis." The United Nations has
      officially declared 2005 as the International Year of Physics. However, the
      impact of Einstein's ideas was not restricted to physics. Among numerous other
      disciplines, Einstein also made significant and specific contributions to Earth
      Sciences. His geosciences-related letters, comments, and scientific articles are
      dispersed, not easily accessible, and are poorly known. The present review
      attempts to integrate them as a tribute to Einstein in commemoration of this
      centenary. These contributions can be classified into three basic areas:
      geodynamics, geological (planetary) catastrophism, and fluvial geomorphology.
      Regarding geodynamics, Einstein essentially supported Hapgood's very
      controversial theory called Earth Crust Displacement. With respect to geological
      (planetary) catastrophism, it is shown how the ideas of Einstein about
      Velikovsky's proposals evolved from 1946 to 1955. Finally, in relation to fluvial
      geodynamics, the review incorporates the elegant work in which Einstein explains
      the formation of meandering rivers. A general analysis of his contributions is
      also carried out from today's perspective. Given the interdisciplinarity and
      implications of Einstein's achievements to multiple fields of knowledge, we
      propose that the year 2005 serve, rather than to confine his universal figure
      within a specific scientific area, to broaden it for a better appreciation of
      this brilliant scientist in all of his dimensions.

PMID- 16453105
TI  - Decay of cacti and carbon cycling.
AB  - Cacti contain large quantities of Ca-oxalate biominerals, with C derived from
      atmospheric CO(2). Their death releases these biominerals into the environment,
      which subsequently transform to calcite via a monohydrocalcite intermediate.
      Here, the fate of Ca-oxalates released by plants in arid environments is
      investigated. This novel and widespread form of biomineralization has unexpected
      consequences on C cycling and calcite accumulation in areas with large numbers of
      cacti. The magnitude of this mineralization is revealed by studying the large
      columnar cactus Carnegiea gigantea (Engelm.) Britton and Rose in southwestern
      Arizona (locally called the saguaro). A large C. gigantea contains on the order
      of 1 x 10(5) g of the Ca-oxalate weddellite-CaC(2)O(4) x 2H(2)O. In areas with
      high C. gigantea density, there is an estimated 40 g C(atm) m(-2) sequestered in
      Ca-oxalates. Following the death of the plant, the weddellite transforms to
      calcite on the order to 10-20 years. In areas with high saguaro density, there is
      an estimated release of up to 2.4 g calcite m(-2) year(-1) onto the desert soil.
      Similar transformation mechanisms occur with the Ca-oxalates that are abundant in
      the majority of cacti. Thus, the total atmospheric C returned to the soil of
      areas with a high number density of cacti is large, suggesting that there may be
      a significant long-term accumulation of atmospheric C in these soils derived from
      Ca-oxalate biominerals. These findings demonstrate that plant decay in arid
      environments may have locally significant impacts on the Ca and inorganic C
      cycles.

PMID- 16453106
TI  - Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and
      mucosal mast cells in rat intestine.
AB  - Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are
      the major anions in the large intestinal lumen. They are produced from dietary
      fiber by bacterial fermentation and are known to have a variety of physiological
      and pathophysiological effects on the intestine. In the present study, we
      investigated the expression of the SCFA receptor, GPR43, in the rat distal ileum
      and colon. Expression of GPR43 was detected by reverse transcriptase/polymerase
      chain reaction (RT-PCR), Western blotting, and immunohistochemistry. mRNA for
      GPR43 was detected, by RT-PCR, in extracts of the whole wall and separated mucosa
      from the ileum and colon and from muscle plus submucosa from the ileum, but not
      from muscle plus submucosa preparations from the colon. We raised a rabbit
      antiserum against a synthesized fragment of rat GPR43; this was specific for rat
      GPR43. GPR43 protein was detected by Western blot analysis in extracts of whole
      wall and separated mucosa, but not in muscle plus submucosa extracts. By
      immunohistochemistry, GPR43 immunoreactivity was localized to enteroendocrine
      cells expressing peptide YY (PYY), whereas 5-hydroxytryptamine (5-HT)
      immunoreactive (IR) enteroendocrine cells were not immunoreactive for GPR43. Mast
      cells of the lamina propria expressing 5-HT were also GPR43-IR. The results of
      the present study suggest that the PYY-containing enteroendocrine cells and 5-HT
      containing mucosal mast cells sense SCFAs via the GPR43 receptor. This is
      consistent with physiological data showing that SCFAs stimulate the release of
      PYY and 5-HT from the ileum and colon.

PMID- 16453107
TI  - Pallial oviduct of Pomacea canaliculata (Gastropoda): ultrastructural studies of
      the parenchymal cellular types involved in the metabolism of perivitellins.
AB  - Seasonal variations in the morphology of the parenchymal mass and function of the
      albumen gland/capsule gland complex have been studied in Pomacea canaliculata,
      together with the cellular types involved in the synthesis and secretion of
      perivitellin fluid components. The two major parenchymal cell types, albumen
      secretory cells (AS) and labyrinthic cells (LC), undergo seasonal variations
      throughout the annual reproductive cycle, which is divided into three periods.
      Both cellular types show maximal development and structural complexity during the
      reproductive period (spring and summer). AS cells have a well-developed Golgi
      complex and rough endoplasmic reticulum and their secretory granules show
      electron-dense particles of about 20 nm (probably galactogen). These cells are
      uniquely involved in ovorubin and PV2 perivitellin synthesis and their secretory
      granules are the single storage site for these two major perivitellins, as
      revealed by immunoelectron microscopy. AS also possess calcium deposits that
      infiltrate the cytoplasmic matrix. The luminal surfaces of LC exhibit long cilia
      intermingled with sparce short microvilli. Basally, the plasma membrane shows
      deep irregular folds that extend through the cytoplasm up to the subapical
      region. Calcium deposits infiltrate the cytoplasm and accumulate in the
      extracellular space of the basal labyrinth. Nerve terminals seem to be involved
      in the regulation of parenchymal cell secretion. At the post-reproductive period,
      AS markedly change their aspect following the release of most of the secretory
      granules into the acinar lumen. LC decrease in volume, the number of their cilia
      decreases, their cytoplasmic folds are much thinner and their extracellular
      spaces lack calcium particles. At the pre-reproductive period (winter), AS and LC
      recover and prepare for the subsequent period.

PMID- 16453108
TI  - [Pulmonary segmental mediolytic arteriopathy].
AB  - Segmental mediolytic arteriopathy (SMA) is defined as non-inflammatory
      arteriopathy with mediolysis due to segmental loss of media and consecutive
      formation of vascular gaps. Up to now, less than 40 cases of visceral and
      cerebral SMA and, to our knowledge, only one case of pulmonary SMA have been
      reported. We present the history of a 21 year old female patient, admitted to
      hospital with hemoptysis, but without other symptoms. Apart from two lesions in
      the sixth and tenth pulmonary segment, documented by CT and interpreted as
      colliquations, there were no other clinical and laboratory findings. Repeated
      bronchoscopy supplied no further information. Histomorphology of the resected
      lesion revealed SMA without evidence of vasculitis. Wegener's disease could be
      excluded. The aetiology of the disease is still unknown. Acute vasospasm (due to
      inappropriate reactions to catecholamine or endothelial dysfunction), as well as
      SMA as a precursor or subtype of fibromuscular dysplasia, are two theories still
      under discussion.

PMID- 16453109
TI  - [Expression of angiotensin I converting enzyme in pulmonary hypertension].
AB  - We studied angiotensin I converting enzyme (ACE) expression in lung tissue from
      patients with different forms of pulmonary hypertension (PH) in comparison with
      that from morphologically normal lung specimens. ACE antigen expression was
      analysed by immunohistochemistry in morphologically normal lung tissue from 33
      patients (19 males, 32-77 years; 14 females, 34-93 years) and compared to that in
      specimens from 94 patients (67 males, 30-97 years; 27 females: 27-90 years) with
      different clinically proven forms of PH (according to Venedig classification).
      Type specific vessel expression pattern as described for normal lung tissue was
      generally intensified in arteries, arterioles and capillaries of the lung
      specimens with PH. Specimens with PH due to left heart disease and chronic
      obstructive pulmonary disease (COPD) showed only very weak or no augmented
      arterial ACE expression, while PH due to collagenoses or interstitial lung
      disease showed significantly higher ACE expression. In human PH there is-
      comparable to animal models--a raised ACE expression in pulmonary lung vessels,
      with differences between the various forms of PH. These differences in ACE
      expression may be relevant for subtly differentiated therapeutic anti-ACE therapy
      regimes.

PMID- 16453110
TI  - Role of intraoperative neurophysiology in primary surgery for obstetrical
      brachial plexus palsy (OBPP).
AB  - OBJECTIVE: Management of conducting neuroma-in-continuity in primary surgery for
      obstetrical brachial plexus palsy (OBPP) is still discussed controversially. We
      present our experience with intraoperative neurophysiological recordings in the
      management of lesions in continuity in OBPP. METHODS: A series of ten children
      with lesions in continuity of the upper brachial plexus is presented. Due to
      recordable compound nerve action potentials (CNAPs) and muscle response to motor
      stimulation across the neuroma, five children underwent external neurolysis of
      neuroma only (neurolysis group). Due to lack of recordable CNAPs or muscle
      response, resection of neuroma and interpositional nerve grafting were performed
      in another five children (resection and grafting group). Functional recovery
      after at least 30 months of follow-up was assessed. RESULTS: There was a marked
      difference in functional recovery between the neurolysis and the resection and
      grafting group. Especially, recovery of shoulder function was disappointing after
      external neurolysis of conducting neuroma-in-continuity. At the end of follow-up,
      results of shoulder and elbow function after resection of neuroma followed by
      interpositional nerve grafting were better without exception. CONCLUSION:
      Intraoperative neurophysiological recordings face certain difficulties when used
      in small children with OBPP. Due to overoptimistic assessment of prognosis after
      intraoperative CNAP recordings and motor stimulation, the functional results
      after neurolysis of conducting neuroma-in-continuity are disappointing. Resection
      of neuroma-in-continuity, conducting or not, offers the best opportunity for
      maximal functional recovery of the compromised upper limb in OBPP. The role of
      intraoperative neurophysiological techniques should be confined to the diagnosis
      of root avulsions.

PMID- 16453111
TI  - Midline cutaneous lumbosacral lesions: not always a sign of occult spinal
      dysraphism.
AB  - OBJECTIVE: The authors report two unusual cases of extraspinal midline
      lumbosacral lesions that resembled the usual skin markers of occult spina bifida.
      PATIENTS AND METHODS: The pathological diagnosis of the masses was plexiform
      neurofibroma and mastocytoma, respectively. RESULTS: Some lesions, as those we
      are reporting, although occurring at the lumbosacral midline, do not necessarily
      belong to occult spinal dysraphism, as was initially suspected. Plexiform
      neurofibroma and skin mastocytoma are very rare indeed in this spinal location.
      CONCLUSION: The two cases represent an important addition to the differential
      diagnosis of a congenital dorsal midline mass.

PMID- 16453113
TI  - Structure and expression of two genes encoding secreted acid phosphatases under
      phosphate-deficient conditions in Pholiota nameko strain N2.
AB  - Twenty-three polypeptides secreted in response to a deficiency of inorganic
      phosphate (Pi) were previously found by two-dimensional polyacrylamide gel
      electrophoresis analysis in mycelia of Pholiota nameko strain N2. In this study,
      N-terminal sequencing revealed three of them to be identical to known acid
      phosphatases of P. nameko strain N114. Two cDNAs and the corresponding genomic
      DNAs of genes PNAP1 and PNAP2 which encode two of the three acid phosphatases
      were cloned. The deduced amino acid sequences of PNAP1 and PNAP2 showed high
      similarity to other fungal acid phosphatases and contained a putative catalytic
      active site of acid phosphatase. PNAP1 and PNAP2 are comprised of five and seven
      exons interrupted by four and six introns, respectively. Their promoter regions
      include two cis-acting elements found in Pi deficiency-inducible genes of
      Saccharomyces cerevisiae, together with several known functional elements such as
      a TATA box. Northern blot analysis showed that PNAP1 and PNAP2 are expressed in
      response to a deficiency of Pi.

PMID- 16453112
TI  - Chlamydomonas reinhardtii encodes a single sigma70-like factor which likely
      functions in chloroplast transcription.
AB  - Chlamydomonas reinhardtii EST clones encoding a protein highly similar to
      prokaryotic sigma factors and plant sigma-like factors (SLFs) were used to
      isolate a BAC clone containing the full-length gene CrRpoD. The gene is likely to
      be single-copy, in contrast to small gene families encoding SLFs in plants. The
      CrRpoD mRNA comprises 3,033 nt with an open reading frame of 2,256 nt, encoding a
      putative protein of 752 amino acids with a molecular mass of 80.2 kDa. The
      sequence contains conserved regions 2-4 typically found in sigma factors, and an
      unusually long amino terminal extension, which by in silico analysis has
      properties of a chloroplast transit peptide. Expression of CrRpoD was confirmed
      by immunodetection of a 85 kDa polypeptide in a preparation enriched for
      chloroplast proteins. To demonstrate functionality in transcription initiation, a
      recombinant CrRpoD-thioredoxin fusion protein was reconstituted with E. coli RNA
      polymerase core enzyme and tested in vitro. This chimeric holoenzyme specifically
      bound the spinach psbA and Chlamydomonas rrn16 promoters in gel mobility shift
      assays and exhibited specific transcription initiation from the same two
      promoters, providing evidence for the role of CrRpoD as a functional
      transcription factor.

PMID- 16453114
TI  - Development of a kinetic metabolic model: application to Catharanthus roseus
      hairy root.
AB  - A kinetic metabolic model describing Catharanthus roseus hairy root growth and
      nutrition was developed. The metabolic network includes glycolysis, pentose
      phosphate pathway, TCA cycle and the catabolic reactions leading to cell building
      blocks such as amino acids, organic acids, organic phosphates, lipids and
      structural hexoses. The central primary metabolic network was taken at pseudo
      steady state and metabolic flux analysis technique allowed reducing from 31
      metabolic fluxes to 20 independent pathways. Hairy root specific growth rate was
      described as a function of intracellular concentration in cell building blocks.
      Intracellular transport and accumulation kinetics for major nutrients were
      included. The model uses intracellular nutrients as well as energy shuttles to
      describe metabolic regulation. Model calibration was performed using experimental
      data obtained from batch and medium exchange liquid cultures of C. roseus hairy
      root using a minimal medium in Petri dish. The model is efficient in estimating
      the growth rate.

PMID- 16453116
TI  - Ruptured fusiform aneurysm of fenestrated A1 segment of the anterior cerebral
      artery. Case report and review of the literature.
AB  - We present a case report of a 56-year-old woman with a ruptured fusiform aneurysm
      of a fenestrated A(1) segment of the anterior cerebral artery (ACA). Fenestrated
      A(1) segments are rare and only a few case reports have been published of a
      saccular type aneurysm formation. To the best of our knowledge, there have been
      no documented cases of fusiform aneurysms in these segments.

PMID- 16453115
TI  - Detection and characterization of liver metastases: 16-slice multidetector
      computed tomography versus superparamagnetic iron oxide-enhanced magnetic
      resonance imaging.
AB  - The aim of our study was to compare the diagnostic performance of 16--slice
      multidetector computed tomography with that of superparamagnetic iron oxide
      (SPIO)-enhanced magnetic resonance (MR) imaging in the detection of small hepatic
      metastases and in the differentiation of hepatic metastases from cysts. Twenty
      three patients with 55 liver metastases and 14 liver cysts underwent SPIO
      enhanced MR imaging and multiphasic CT using 16-MDCT. Two observers independently
      analyzed each image, in random order. Sensitivity and diagnostic accuracy for
      lesion detection and differentiation as metastases or cysts for MDCT and SPIO
      enhanced MR imaging were calculated using receiver operating characteristic
      analysis. For all observers, the Az values of SPIO-enhanced MR imaging for lesion
      detection and differentiation of liver metastases from cysts (mean 0.955, 0.999)
      were higher than those of MDCT (mean 0.925, 0.982), but not statistically
      significantly so (P > 0.05). Sensitivity of SPIO-enhanced MR imaging with regard
      to the detection of liver metastases (mean 94.5%) was significantly higher than
      that of MDCT (mean 80.0%) (P < 0.05). SPIO-enhanced MR imaging and 16-MDCT showed
      similar diagnostic accuracies for detection and differentiation of liver
      metastases from cysts, but sensitivity of SPIO-enhanced imaging in the detection
      of liver metastases was superior to that of 16-MDCT.

PMID- 16453117
TI  - Assessment of vasospasm in experimental subarachnoid hemorrhage in rats by
      selective biplane digital subtraction angiography.
AB  - Although the rat subarachnoid hemorrhage model is well established in vasospasm
      research, the angiographic evaluation is difficult due to the animal's small
      size. For this reason, the aim of the study was to develop a standardized
      angiographic examination technique without additional complex equipment. Under
      general anesthesia, 11 Sprague-Dawley rats underwent selective cerebral digital
      subtraction angiography using a 0.3 mm focal spot and a 2.0-fold linear
      magnification. Five animals had experimental subarachnoid hemorrhage according to
      the "double-hemorrhage" model. Comparison with the intraarterial tip of the
      microcatheter enabled calibration of the vessel lumen. The diameter of the normal
      basilar artery (n=6) was 0.34+/-0.03 mm (mean+/-SD), whereas delayed vasospastic
      constriction (mean 6.2 days) caused a reduction in diameter of 32.4% (0.23+/-0.09
      mm) as well as impaired collateral blood flow via the posterior communicating
      artery and anterior spinal artery. Histological examination of sections stained
      with hematoxylin and eosin under a light microscope confirmed vasospasm. In
      conclusion, biplane digital subtraction angiography allows precise and reliable
      evaluation of arterial diameter reduction and hemodynamic parameters in a rat
      vasospasm model. However, further investigation is required for assessment of
      vasoactive drugs, e.g., endothelin receptor antagonists.

PMID- 16453118
TI  - Beaked whale auditory evoked potential hearing measurements.
AB  - Several mass strandings of beaked whales have recently been correlated with
      military exercises involving mid-frequency sonar highlighting unknowns regarding
      hearing sensitivity in these species. We report the hearing abilities of a
      stranded juvenile beaked whale (Mesoplodon europaeus) measured with auditory
      evoked potentials. The beaked whale's modulation rate transfer function (MRTF)
      measured with a 40-kHz carrier showed responses up to an 1,800 Hz amplitude
      modulation (AM) rate. The MRTF was strongest at the 1,000 and 1,200 Hz AM rates.
      The envelope following response (EFR) input-output functions were non-linear. The
      beaked whale was most sensitive to high frequency signals between 40 and 80 kHz,
      but produced smaller evoked potentials to 5 kHz, the lowest frequency tested. The
      beaked whale hearing range and sensitivity are similar to other odontocetes that
      have been measured.

PMID- 16453119
TI  - Crosstalk between metal ions in Bacillus subtilis ferrochelatase.
AB  - Ferrochelatase (EC 4.99.1.1), the terminal enzyme in the heme biosynthetic
      pathway, catalyzes the insertion of Fe2+ into protoporphyrin IX, generating heme.
      In vitro assays have shown that all characterized ferrochelatases can also
      incorporate Zn2+ into protoporphyrin IX. Previously Zn2+ has been observed at an
      inner metal binding site close to the porphyrin binding site. Mg2+, which
      stimulates Zn2+ insertion by Bacillus subtilis ferrochelatase, has been observed
      at an outer metal binding site. Exchange of Glu272 to a serine eliminated the
      stimulative effect of Mg2+. We found that Zn2+ quenched the fluorescence of B.
      subtilis ferrochelatase and this quenching was used to estimate the metal
      affinity. Trp230 was identified as the intrinsic fluorophore responsible for the
      observed quenching pattern. The affinity for Zn2+ could be increased by
      incubating the ferrochelatase with the transition state analogue N-methyl
      mesoporphyrin IX, which reflected a close collaborative arrangement between the
      two substrates in the active site. We also showed that the affinity for Zn2+ was
      lowered in the presence of Mg2+ and that bound Zn2+ was released upon binding of
      Mg2+. In the ferrochelatase with a Glu272Ser modification, the interaction
      between Zn2+ and Mg2+ was abolished. It could thereby be demonstrated that the
      presence of a metal at one metal binding site affected the metal affinity of
      another, providing the enzyme with a site that regulates the enzymatic activity.

PMID- 16453121
TI  - Batch and repeated batch production of L (+)-lactic acid by Enterococcus faecalis
      RKY1 using wood hydrolyzate and corn steep liquor.
AB  - Lactic acid production was investigated for batch and repeated batch cultures of
      Enterococcus faecalis RKY1, using wood hydrolyzate and corn steep liquor. When
      wood hydrolyzate (equivalent to 50 g l(-1) glucose) supplemented with 15-60 g l(
      1) corn steep liquor was used as a raw material for fermentation, up to 48.6 g l(
      1) of lactic acid was produced with, volumetric productivities ranging between
      0.8 and 1.4 g l(-1 )h(-1). When a medium containing wood hydrolyzate and 15 g l(
      1) corn steep liquor was supplemented with 1.5 g l(-1) yeast extract, we observed
      1.9-fold and 1.6-fold increases in lactic acid productivity and cell growth,
      respectively. In this case, the nitrogen source cost for producing 1 kg lactic
      acid can be reduced to 23% of that for fermentation from wood hydrolyzate using
      15 g l(-1) yeast extract as a single nitrogen source. In addition, lactic acid
      productivity could be maximized by conducting a cell-recycle repeated batch
      culture of E. faecalis RKY1. The maximum productivity for this process was
      determined to be 4.0 g l(-1 )h(-1).

PMID- 16453120
TI  - Desulfovibrio gigas ferredoxin II: redox structural modulation of the [3Fe-4S]
      cluster.
AB  - Desulfovibrio gigas ferredoxin II (DgFdII) is a small protein with a polypeptide
      chain composed of 58 amino acids, containing one Fe3S4 cluster per monomer. Upon
      studying the redox cycle of this protein, we detected a stable intermediate
      (FdIIint) with four 1H resonances at 24.1, 20.5, 20.8 and 13.7 ppm. The
      differences between FdIIox and FdIIint were attributed to conformational changes
      resulting from the breaking/formation of an internal disulfide bridge. The same
      1H NMR methodology used to fully assign the three cysteinyl ligands of the [3Fe
      4S] core in the oxidized state (DgFdIIox) was used here for the assignment of the
      same three ligands in the intermediate state (DgFdIIint). The spin-coupling model
      used for the oxidized form of DgFdII where magnetic exchange coupling constants
      of around 300 cm-1 and hyperfine coupling constants equal to 1 MHz for all the
      three iron centres were found, does not explain the isotropic shift temperature
      dependence for the three cysteinyl cluster ligands in DgFdIIint. This study,
      together with the spin delocalization mechanism proposed here for DgFdIIint,
      allows the detection of structural modifications at the [3Fe-4S] cluster in
      DgFdIIox and DgFdIIint.

PMID- 16453122
TI  - Metabolism associated with raised metabolic flux to sugar nucleotide precursors
      of exopolysaccharides in Lactobacillus delbrueckii subsp. bulgaricus.
AB  - Exopolysaccharide (EPS) metabolism was studied in a galactose-negative strain of
      Lactobacillus delbrueckii subsp. bulgaricus, using two different approaches.
      Firstly, using both the parent strain and a chemically induced mutant with higher
      yield and specific productivity of EPS than the parent, comparative information
      was obtained relating to enzyme activities and metabolite levels associated with
      EPS formation when grown on lactose. Under continuous culture conditions (D =
      0.10 h(-1)), the higher metabolic flux towards EPS formation in the mutant strain
      relative to the parent appeared to be mediated by raised levels of UDP-glucose
      pyrophosphorylase (UGP). Marginally raised UDP-galactose 4-epimerase (UGE)
      activity in the mutant strain suggested that this enzyme could also play a role
      in EPS overproduction. The second approach involved investigating the effect of
      growth rate on sugar nucleotide metabolism in the parent, as it is known that EPS
      production is growth-associated in this strain. UGE activity in the parent strain
      appeared to increase when the growth rate was elevated from 0.05 to 0.10 h(-1),
      and further to 0.35 h(-1), conditions that can be associated with higher levels
      of metabolic flux to EPS formation. Concurrent with these increments,
      intracellular ATP levels in the cell were raised. In both investigations glucose
      6-phosphate accumulated pointing to a constriction at this branch-point, and a
      limitation in the flow of carbon towards fructose-6-phosphate or glucose-1
      phosphate. The changes in metabolism associated with enhanced flux to EPS provide
      guidance as to how the yield of Lactobacillus delbrueckii subsp. bulgaricus EPS
      can be improved.

PMID- 16453123
TI  - Vehicle of triamcinolone acetonide is associated with retinal toxicity and
      transient increase of lens density.
AB  - BACKGROUND: Intravitreal triamcinolone acetonide (TA) has been widely used as a
      therapeutic method for many ocular diseases, but a consensus on an appropriate
      safe therapeutic window of dosage for intravitreal injection, and whether vehicle
      of TA should be reduced or eliminated, has not yet been reached. The aim of this
      article is to investigate these issues. METHODS: Forty New Zealand white rabbits
      were divided into four experimental groups and one control group. Four or 25 mg
      TA, with vehicle either reduced or not, was injected into the vitreous cavity of
      rabbits in experimental groups. Rabbits in the control group received 0.2 ml
      intravitreal sterile saline solution. Intraocular pressures (IOP) were measured
      by a Tonopen tonometer. Values of lens density were measured by a Pentacam
      system. Soluble protein, total antioxidation capacity, reduced glutathione (GSH),
      glutathion peroxidase (GSH-px), and superoxide dismutase (SOD) in lens were
      measured by specific kits. ERG and pathological examinations, including light and
      electron microscopy of the retina, were also performed. RESULTS: Elevation of IOP
      was noted in all experimental groups after intravitreal TA (P<0.01, paired t
      test). Significant increase of lens density was noticed at 1 week after
      intravitreal TA in the 25 mg vehicle-containing group (P<0.0001, paired t-test).
      Significant loss of GSH-px activity was noticed at the end of the study (P<0.05,
      paired t-test), while SOD activity increased (P<0.05, paired t-test). Amplitudes
      of ERG waves declined significantly in vehicle-containing groups (P<0.01, paired
      t-test) at the end of the study. Pathological examination showed obvious retinal
      toxicity in vehicle-containing groups. CONCLUSIONS: Vehicle of TA should be
      eliminated or reduced before intravitreal injection to avoid potential retinal
      toxicity and transient increase in lens density.

PMID- 16453124
TI  - Influence of a new surface modification of intraocular lenses with
      fluoroalkylsilan on the adherence of endophthalmitis-causing bacteria in vitro.
AB  - INTRODUCTION: Dynasilan is a fluoroalkylsilan that is able to interact with
      surface active centres on intraocular lenses (IOL), offering a new way for
      surface modification of different IOL materials. The purpose of this in vitro
      study was to investigate the influence of this new surface modification on the
      adherence of two typical endophthalmitis causing bacteria (Staphylococcus
      epidermidis, Propionibacterium acnes). MATERIALS AND METHODS: In a pilot
      experiment, the effect of Dynasilan coating on the adherence of S. epidermidis
      was tested on glass slides. Forty-two Dynasilan-modified and 42 unmodified IOL
      (14 PMMA, 14 silicone and 14 hydrogel) were incubated at 37 degrees C in brain
      heart infusion broth (10(8) CFU/ml) with either S. epidermidis for 24 h or with
      P. acnes for 1 h. Subsequently, the adherent bacteria were resuspended using
      ultrasonification at 35 kHz for 3x45 s. After dilution series and incubation at
      37 degrees C on Petri dishes for 24 h and 3 days, respectively, the colonies were
      counted. RESULTS: In the pilot experiment, a markedly lower number of adherent S.
      epidermidis was observed on Dynasilan-modified glass slides. Of all IOL materials
      incubated with S. epidermidis, those modified with Dynasilan showed a lower mean
      number of adherent bacteria (mean 1.37x10(7); SD 2.37x10(7)) than those untreated
      (2.43x10(7); SD 3.04x10(7)). IOLs incubated with P. acnes showed a significantly
      lower mean number of adherent bacteria of 2.51x10(4) (SD 2.71x10(4)) on Dynasilan
      modified IOLs versus 6.27x10(4) (SD 7.70x10(4)) on untreated IOLs. CONCLUSION:
      The presented in vitro results indicate that Dynasilan surface modification is
      able to reduce the adherence of S. epidermidis and P. acnes on all IOL materials
      tested. Further studies regarding the stability of this modification and its
      biocompatibility must be performed.

PMID- 16453125
TI  - Congenital cataract and macular hypoplasia in humans associated with a de novo
      mutation in CRYAA and compound heterozygous mutations in P.
AB  - BACKGROUND: An isolated form of congenital cataract associated with macular
      hypoplasia and a generally hypopigmented fundus in infancy was observed in a
      German family. To test the hypothesis that a de-novo mutation had occurred in one
      of the parental germ lines, a functional candidate gene approach was applied.
      METHODS: The family was carefully examined by a senior paediatric ophthalmologist
      according to routine procedures (slit lamp, funduscopy, ERG). Blood was taken
      from the proband and his parents, genomic DNA was isolated and some candidate
      genes for cataract (CRYAA, CRYBB2, GJA8) or macular hypoplasia (OA1, P) or both
      (PAX6) were analyzed. RESULTS: The proband showed bilateral cataracts at the age
      of 4 months; the fundus appeared pale, the optic disc grayish, and macular
      reflexes were absent. After cataract surgery, the nystagmus persisted, and a
      control ERG at age 9 years showed essentially normal scotopic and photopic wave
      forms. An infectious aetiology as well as galactosemia were excluded. However, a
      heterozygous mutation was found in the proband in exon 1 of CRYAA (62 C-->T),
      which leads to an exchange from Arg to Leu at amino acid position 21 (R21L). This
      sequence alteration was not found in the parents and in 96 randomly selected DNA
      samples from ophthalmologically normal individuals of the KORA S4 study
      population. In addition, two heterozygous mutations in P were identified (R419Q
      and A481T); one of both was present in each of the unaffected parents.
      CONCLUSION: Based upon the unique finding of the mutation and the expression of
      CRYAA in the lens, this R21L mutation in the CRYAA is considered to be causative
      for the dominant cataract phenotype. Moreover, the macular hypoplasia has to be
      considered a concerted interaction with compound heterozygous mutations in the P
      gene manifesting a mild form of oculocutaneous albinism. Nevertheless, this
      combination is rare and future studies will focus on identifying similar
      phenotypes.

PMID- 16453126
TI  - Congenital macular macrovessels.
AB  - BACKGROUND: Congenital aberrant macular vessels are rare and may cause visual
      impairment when crossing the fovea, when causing the formation of foveolar cysts,
      or when haemorrhage occurs. METHODS: From the records of patients with vascular
      anomalies seen at the Retina Department of the University Federico II in Naples
      from 1980 to 2005, we reviewed all cases presenting an abnormal, large, retinal
      vessel crossing the macular region. RESULTS: An anomalous macular macrovessel was
      present in 13 cases. Follow-up ranged from 3 months to 21 years (mean 14 years).
      In all cases the abnormal vessel was a vein, presenting a fluoroangiographic
      early filling and delayed emptying. In some cases there were microvascular bed
      anomalies, such as enlargement of the foveal avascular zone, focal capillary
      dilation, or microaneurysmal abnormalities. In one case late, mild, intraretinal
      staining along the anomalous vessel indicated retinal oedema. Visual impairment
      occurred in five eyes, being caused by a preretinal haemorrhage in one case and
      by the mere presence of the macrovessel in the foveal area in four cases, and had
      not improved at following controls. CONCLUSION: In the presence of an aberrant
      vessel crossing the macular region, visual acuity and ophthalmoscopic and
      fluoroangiographic findings tend to have remained stable at long-term follow-up.

PMID- 16453127
TI  - Lens dislocation following trauma sustained 40 years ago during cataract surgery
      pre-assessment.
AB  - BACKGROUND: To report a case of spontaneous lens dislocation following pupillary
      dilatation during preoperative assessment for cataract surgery. METHODS: Our
      patient had been punched on the left side of the face 40 years ago but throughout
      this period the patient's vision had remained normal and ophthalmic evaluation by
      opticians had also been normal on multiple visits. He was referred to our clinic
      for cataract assessment. Detailed ophthalmic evaluation, including pupillary
      dilatation with fundus evaluation,had revealed no evidence of anterior or
      posterior segment trauma. RESULTS: He presented 1 week later with lens
      dislocation. The dislocated lens was successfully removed. CONCLUSION: We
      recommend that caution be exercised (even in the presence of normal ophthalmic
      evaluation) when dilating patients with an apparently trivial/or old history of
      trauma to the face.

PMID- 16453128
TI  - TFF peptides and mucins are major components of dacryoliths.
AB  - PURPOSE: The study was performed to determine whether trefoil factor peptides
      (TFF) and/or mucins are components of dacryoliths and to gain further insight
      into dacryolith composition and formation. METHODS: Twenty dacryoliths found in
      lacrimal surgery in patients suffering from primary acquired nasolacrimal duct
      obstruction were analyzed for the presence of TFF peptides (TFF1, 2, 3), mucins
      (MUC1, 2, 3, 4, 5AC, 5B, 6, 7, 8), defense cells (T- and B lymphocytes,
      macrophages, neutrophils), and antimicrobial substances (alpha defensins 1-3,
      secretory phospholipase A(2)) by means of light microscopy, histochemistry,
      immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR)
      and real-time PCR. RESULTS: All dacryoliths except one revealed clear
      immunoreactivity for all three TFF peptides. The immunohistochemical distribution
      of mucins was inhomogeneous throughout the different dacryoliths. However, in
      some dacryoliths all mucins investigated were detected. MUC8 showed reactivity in
      14 out of 15 dacryoliths analyzed by immunohistochemistry. Most dacryoliths
      contained alpha defensins 1-3 as the secretory product of neutrophils. T and B
      lymphocytes, macrophages and secretory phospholipase A(2) were only present in
      single dacryoliths. Quantification of TFF peptide expression supported the
      immunohistochemical finding that all three TFF peptides are augmented in
      dacryoliths. CONCLUSIONS: Dacryoliths consist partly of secreted mucins
      comparable with the mucin spectrum of the epithelium of healthy nasolacrimal
      ducts. Beside TFF1 and TFF3, both of which are produced under healthy
      circumstances, TFF2 is additionally induced and secreted in cases of
      dacryolithiasis. All three TFF peptides appear to be augmented in dacryoliths.
      With regard to their rheologic properties, TFF peptides may play a functional
      role in dacryolith formation. However, our results raise the question of whether
      TFF peptides per se influence dacryolith formation or whether their secretion, as
      in secretion of mucins and alpha defensins 1-3, is merely a secondary phenomenon.

PMID- 16453129
TI  - Effects of the protein tyrosine kinase inhibitor genistein and taurine on retinal
      function in isolated superfused retina.
AB  - BACKGROUND: Genistein has the potential to act as an intraocular antiangiogenic
      agent. Its therapeutical use, however, is limited by toxic side effects on the
      retina. This study was designed to evaluate the simultaneous use of taurine as a
      neuroprotective drug. METHODS: Bovine retinas were isolated and perfused with an
      oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded
      as a transretinal electrical potential using Ag/AgCl electrodes. At stable ERG
      amplitudes, genistein at concentrations of 11, 37, and 150 microM was added to
      the nutrient solution for 45 min, in the absence or presence of taurine (3 mM).
      Thereafter, the retina was reperfused with the nutrient solution for another 100
      min. The percentage of b-wave reduction during genistein and genistein/taurine
      application was calculated. RESULTS: The b-wave amplitude was reduced by a
      smaller amount during the application of genistein (11 and 37 microM) in the
      presence of taurine compared with genistein alone. For both, genistein/taurine
      and genistein alone the b-wave recovered completely during the wash-out of the
      drugs. However, during the application of the highest tested concentration of
      genistein (150 microM), taurine did not protect completely, leading to an
      irreversible b-wave reduction. CONCLUSIONS: The adjuvant use of taurine reduces
      the genistein-induced retinal toxicity to a certain degree. However, the
      protective effect of taurine is limited and there is only a narrow therapeutic
      index for a combined intravitreal administration of genistein in coapplication
      with taurine to inhibit pathological ocular neovascularization.

PMID- 16453130
TI  - Potato chromosomes IX and XI carry genes for resistance to potato virus M.
AB  - Two new loci for resistance to potato virus M (PVM), Gm and Rm, have been mapped
      in potato. The gene Gm was derived from Solanum gourlayi, whereas, Solanum
      megistacrolobum is the source of the gene Rm. Gm confers resistance to PVM
      infection after mechanical inoculation. Rm induces a hypersensitive response in
      potato plants. Two diploid populations segregating for Gm and Rm, bulked
      segregant analysis (BSA) using random amplified polymorphic DNA (RAPD) and inter
      simple sequence repeat (ISSR), and available potato molecular maps were
      instrumental for mapping the resistance loci. The novel locus Gm was mapped to a
      central region on potato chromosome IX. The locus Rm was placed on the short arm
      of chromosome XI, close to the marker loci GP250 and GP283, where a hotspot for
      monogenic and polygenic resistance to diverse pathogens is located in the potato
      and tomato genome.

PMID- 16453132
TI  - GS3, a major QTL for grain length and weight and minor QTL for grain width and
      thickness in rice, encodes a putative transmembrane protein.
AB  - The GS3 locus located in the pericentromeric region of rice chromosome 3 has been
      frequently identified as a major QTL for both grain weight (a yield trait) and
      grain length (a quality trait) in the literature. Near isogenic lines of GS3 were
      developed by successive crossing and backcrossing Minghui 63 (large grain) with
      Chuan 7 (small grain), using Minghui 63 as the recurrent parent. Analysis of a
      random subpopulation of 201 individuals from the BC3F2 progeny confirmed that the
      GS3 locus explained 80-90% of the variation for grain weight and length in this
      population. In addition, this locus was resolved as a minor QTL for grain width
      and thickness. Using 1,384 individuals with recessive phenotype (large grain)
      from a total of 5,740 BC3F2 plants and 11 molecular markers based on sequence
      information, GS3 was mapped to a DNA fragment approximately 7.9 kb in length. A
      full-length cDNA corresponding to the target region was identified, which
      provided complete sequence information for the GS3 candidate. This gene consists
      of five exons and encodes 232 amino acids with a putative PEBP-like domain, a
      transmembrane region, a putative TNFR/NGFR family cysteine-rich domain and a VWFC
      module. Comparative sequencing analysis identified a nonsense mutation, shared
      among all the large-grain varieties tested in comparison with the small grain
      varieties, in the second exon of the putative GS3 gene. This mutation causes a
      178-aa truncation in the C-terminus of the predicted protein, suggesting that GS3
      may function as a negative regulator for grain size. Cloning of such a gene
      provided the opportunity for fully characterizing the regulatory mechanism and
      related processes during grain development.

PMID- 16453131
TI  - Detection of QTLs for grain protein content in durum wheat.
AB  - Grain protein content (GPC) of durum wheat (Triticum turgidum L. var. durum) is
      an important trait for the nutritional value of grain and for influencing the
      technological property of flour. Protein content is a quantitative trait
      negatively correlated with grain yield, thus increase in protein quantity usually
      results in yield reduction. This study was initiated to introgress alleles for
      high GPC from var. dicoccoides into durum wheat germplasm by the backcross inbred
      line (BIL) method and to identify molecular markers linked to high GPC alleles
      not associated with depressing effects on yield. The backcross line 3BIL-85 with
      high GPC and similar grain yield to the recurrent parent was backcrossed to
      Latino, and the generations F2, F3 and F4 were evaluated for GPC and yield per
      spike (GYS) in three field trials. Three QTLs with major effects on GPC were
      detected on chromosome arms 2AS, 6AS and 7BL, identified by the markers Xcfa2164,
      XP39M37 (250) and Xgwm577, respectively. Multiple regression analysis indicated
      that the three QTLs explained all the genetic variances of the trait. The high
      GPC parental line 3BIL-85 was not significantly different from the recurrent
      parent Latino for GYS, but the phenotypic correlation coefficient between GPC and
      GYS had negative values (from -0.02 to -0.28) in each trial, although it was
      statistically significant only in the F3 progeny trial. No co-located QTL for GYS
      was detected, excluding the hypothesis that the putative QTLs for GPC were
      indirect QTLs for low grain yield. The negative protein-yield response could be
      due to: (a) co-location of grain yield per spike QTLs with reduced phenotypic
      effects not detectable by the experimental design or statistical procedures, or
      to (b) opposite pleiotropic gene effects due to the major bio-energetic
      requirements for synthesis of protein then carbohydrates. Mapping loci by BILs
      should enable the production of near-isogenic lines in which the individual
      effects of each QTL can be examined in detail without confounding variations due
      to other putative QTLs.

PMID- 16453133
TI  - Utilization of the three high-throughput SNP genotyping methods, the GOOD assay,
      Amplifluor and TaqMan, in diploid and polyploid plants.
AB  - The application of high-throughput SNP genotyping is a great challenge for many
      research projects in the plant genetics domain. The GOOD assay for mass
      spectrometry, Amplifluor and TaqMan are three methods that rely on different
      principles for allele discrimination and detection, specifically, primer
      extension, allele-specific PCR and hybridization, respectively. First, with the
      goal of assessing allele frequencies by means of SNP genotyping, we compared
      these methods on a set of three SNPs present in the herbicide resistance genes
      CSR, AXR1 and IXR1 of Arabidopsis thaliana. In this comparison, we obtained the
      best results with TaqMan based on PCR specificity, flexibility in primer design
      and success rate. We also used mass spectrometry for genotyping polyploid
      species. Finally, a combination of the three methods was used for medium- to high
      throughput genotyping in a number of different plant species. Here, we show that
      all three genotyping technologies are successful in discriminating alleles in
      various plant species and discuss the factors that must be considered in
      assessing which method to use for a given application.

PMID- 16453134
TI  - Evidence for a large-scale population structure of Arabidopsis thaliana from
      genome-wide single nucleotide polymorphism markers.
AB  - Population-based methods for the genetic mapping of adaptive traits and the
      analysis of natural selection require that the population structure and
      demographic history of a species are taken into account. We characterized
      geographic patterns of genetic variation in the model plant Arabidopsis thaliana
      by genotyping 115 genome-wide single nucleotide polymorphism (SNP) markers in 351
      accessions from the whole species range using a matrix-assisted laser
      desorption/ionization time-of-flight assay, and by sequencing of nine unlinked
      short genomic regions in a subset of 64 accessions. The observed frequency
      distribution of SNPs is not consistent with a constant-size neutral model of
      sequence polymorphism due to an excess of rare polymorphisms. There is evidence
      for a significant population structure as indicated by differences in genetic
      diversity between geographic regions. Accessions from Central Asia have a low
      level of polymorphism and an increased level of genome-wide linkage
      disequilibrium (LD) relative to accessions from the Iberian Peninsula and Central
      Europe. Cluster analysis with the structure program grouped Eurasian accessions
      into K = 6 clusters. Accessions from the Iberian Peninsula and from Central Asia
      constitute distinct populations, whereas Central and Eastern European accessions
      represent admixed populations in which genomes were reshuffled by historical
      recombination events. These patterns likely result from a rapid postglacial
      recolonization of Eurasia from glacial refugial populations. Our analyses suggest
      that mapping populations for association or LD mapping should be chosen from
      regional rather than a species-wide sample or identified genetically as sets of
      individuals with similar average genetic distances.

PMID- 16453136
TI  - [The role of HTA in German health care. Do we need impact objectives?].
AB  - Like other health technologies, HTA should be judged on the quality and size of
      its effects. However, it is only in recent years that this aspect has received
      increased attention. A comprehensive theoretical analysis is still missing. In
      this article national and international studies on the influence of HTA reports
      are presented. On the basis of theoretical models, the thesis is developed that
      the potential of HTA reports is much more extensive and complex than has been
      generally assumed. In order to make use of this potential, a stepwise procedure
      is proposed, comprising the involvement of the groups concerned, the explicit
      inclusion of impact objectives in all HTA reports, and the subsequent evaluation
      of the effects produced. This procedure is illustrated by the example of one HTA
      topic.

PMID- 16453137
TI  - Toward a sustainable European Network for Health Technology Assessment. The
      EUnetHTA project.
AB  - EUnetHTA is a recently initiated EU network aiming at connecting national HTA
      agencies, research institutions, and health ministries to enable an effective
      exchange of information and to lend support to health policy decisions by the
      Member States. The article briefly discusses the policy background, the specific
      objectives, and the project structure of the network.

PMID- 16453138
TI  - Determination of fluoroquinolones in eggs using in-tube solid-phase
      microextraction coupled to high-performance liquid chromatography.
AB  - A simple, rapid, and sensitive method using in-tube solid-phase microextraction
      (in-tube SPME) based on poly(methacrylic acid-ethylene glycol dimethacrylate)
      (MAA-EGDMA) monolith coupled to HPLC with fluorescence and UV detection was
      developed for the determination of five fluoroquinolones (FQs). Ofloxacin (OFL),
      norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENRO), and sarafloxacin
      (SARA) can be enriched and determined in the spiked eggs and albumins. CIP/ENRO
      in eggs and albumins of ENRO-treated hens were also studied using the proposed
      method. Only homogenization, dilution, and centrifugation were required before
      the sample was supplied to the in-tube microextraction, and no organic solvents
      were consumed in the procedures. Under the optimized extraction conditions, good
      extraction efficiency for the five FQs was obtained with no matrix interference
      in the process of extraction and the subsequent chromatographic separation. The
      detection limits (S/N=3) were found to be 0.1-2.6 ng g(-1) and 0.2-2.4 ng g(-1)
      in whole egg and egg albumin, respectively. Good linearity could be achieved over
      the range 2-500 ng mL(-1) for the five FQs with regression coefficients above
      0.9995 in both whole egg and albumin. The reproducibility of the method was
      evaluated at three concentration levels, with the resulting relative standard
      deviations (RSDs) less than 7%. The method was successfully applied to the
      analysis of ENRO and its primary metabolite CIP in the eggs and albumins of ENRO
      treated hens.

PMID- 16453139
TI  - Time delay and partial coherence analyses to identify cortical connectivities.
AB  - Recently it has been demonstrated by Albo that partial coherence analysis is
      sensitive to signal to noise ratio (SNR) and that it will always identify the
      signal with the highest SNR among the three signals as the main (driving)
      influence. We propose to use time delay analysis in parallel to partial coherence
      analysis to identify the connectivities between the multivariate time series.
      Both are applied to a theoretical model (used by Albo) to analyse the connections
      introduced in the model. Time delay analysis identifies the connections
      correctly. We also apply these analyses to the electroencephalogram (EEG) and
      electromyogram of essential tremor patients and EEG of normal subjects while
      bimanually tapping their index fingers. Biologically plausible cortico-muscular
      and cortico-cortical connections are identified by these methods.

PMID- 16453135
TI  - Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in
      chemotherapy-induced damage.
AB  - Intestinal mucositis occurs as a consequence of cytotoxic treatment through
      multiple mechanisms including induction of crypt cell death (apoptosis) and
      cytostasis. The molecular control of these actions throughout the
      gastrointestinal tract has yet to be fully elucidated; however, they are known to
      involve p53, the Bcl-2 family and caspases. This review will provide an overview
      of current research as well as identify areas where gaps in knowledge exist.

PMID- 16453142
TI  - Age-related microvascular degeneration in the human cerebral periventricular
      white matter.
AB  - Clinical studies have identified white matter (WM) lesions as hyperintensive
      regions in the MRI images of elderly patients. Since a cerebrovascular origin was
      attributed to such lesions, the present analysis set out to define the
      microvascular histopathologic changes in the periventricular WM in the aged. Post
      mortem samples of the frontal, parietal, and occipital periventricular WM of 40
      90-year-old subjects were prepared for quantitative light and electron
      microscopy. Light microscopic examination revealed microvascular fibrohyalinosis
      as the most common type of microvascular damage in the elderly. Ultrastructural
      analysis identified the microvascular thickening as collagen deposits affecting
      the basement membrane. The vascular density did not correlate with the age. The
      basement membrane pathology significantly increased, while the number of intact
      microvessels gradually decreased, with advancing age in the frontal and occipital
      WM. Finally, peripheral atherosclerosis coincided with massive microvascular
      fibrosis, particularly in the frontal WM. Our results demonstrate an age-related
      microvascular degeneration in the periventricular WM, which may contribute to the
      development of WM lesions by hindering a sufficient supply of nutrients to the
      affected WM sites. Furthermore, the data accord with previous observations
      identifying the frontal lobe as the site at which WM vulnerability is most
      pronounced. Finally, atherosclerosis in large, peripheral vessels is considered
      to be a predictive marker of microvascular pathology in the WM.

PMID- 16453140
TI  - Anticoagulation strategies in continuous renal replacement therapy: can the
      choice be evidence based?
AB  - OBJECTIVES: Critical illness increases the tendency to both coagulation and
      bleeding, complicating anticoagulation for continuous renal replacement therapy
      (CRRT). We analyzed strategies for anticoagulation in CRRT concerning
      implementation, efficacy and safety to provide evidence-based recommendations for
      clinical practice. METHODS: We carried out a systematic review of the literature
      published before June 2005. Studies were rated at five levels to create
      recommendation grades from A to E, A being the highest. Grades are labeled with
      minus if the study design was limited by size or comparability of groups. Data
      extracted were those on implementation, efficacy (circuit survival), safety
      (bleeding) and monitoring of anticoagulation. RESULTS: Due to the quality of the
      studies recommendation grades are low. If bleeding risk is not increased,
      unfractionated heparin (activated partial thromboplastin time, APTT, 1-1.4 times
      normal) or low molecular weight heparin (anti-Xa 0.25-0.35 IU/l) are recommended
      (grade E). If facilities are adequate, regional anticoagulation with citrate may
      be preferred (grade C). If bleeding risk is increased, anticoagulation with
      citrate is recommended (grade D(-)). CRRT without anticoagulation can be
      considered when coagulopathy is present (grade D(-)). If clotting tendency is
      increased predilution or the addition of prostaglandins to heparin may be helpful
      (grade C(-)). CONCLUSION: Anticoagulation for CRRT must be tailored to patient
      characteristics and local facilities. The implementation of regional
      anticoagulation with citrate is worthwhile to reduce bleeding risk. Future trials
      should be randomized and should have sufficient power and well defined endpoints
      to compensate for the complexity of critical illness-related pro- and
      anticoagulant forces. An international consensus to define clinical endpoints is
      advocated.

PMID- 16453143
TI  - Comparative pathogenesis of recombinant rabies vaccine strain SAD-L16 and SAD-D29
      with replacement of Arg333 in the glycoprotein after peripheral inoculation of
      neonatal mice: less neurovirulent strain is a stronger inducer of neuronal
      apoptosis.
AB  - Less neurovirulent strains of rabies virus have been recognized to be stronger
      inducers of neuronal apoptosis in vitro than more neurovirulent strains, but few
      studies have clarified whether this also applies in vivo. A comparative study was
      performed in two-day-old ICR mice inoculated in a hindlimb thigh muscle with
      recombinant rabies virus vaccine strain SAD-L16 (L16) or SAD-D29 (D29), which
      contains an attenuating substitution of Arg333 in the rabies virus glycoprotein.
      Histopathological and immunohistochemical analyses of brains were performed at
      early daily time points and in moribund animals. Both viruses caused progressive
      limb weakness; mortality with L16 was 100% at day 7 post-inoculation (p.i.) and
      75% at 17 days p.i. for D29 and Kaplan-Meyer survival curves were significantly
      different. L16 spread to the brain more quickly than D29, and both viruses
      produced multifocal lesions in the brainstem and cerebellum associated with
      inflammatory changes and neuronal apoptosis. There was more disseminated
      involvement of the brain and many more infected neurons in L16 infection,
      particularly in the neostriatum, hippocampus, and cerebral cortex. Both viruses
      induced neuronal apoptosis, which was most marked in the brainstem tegmentum and
      internal granular layer of the cerebellum. In light of the lower burden of
      infection and smaller number of neurons infected with D29, this less virulent
      virus was a stronger inducer of neuronal apoptosis than the more virulent L16.
      These findings support previous in vitro studies indicating that there is an
      inverse relationship between pathogenicity and apoptosis. Induction of apoptosis,
      which is an innate mechanism in which the host restricts viral spread, may
      contribute to severe clinical neurological disease when there is viral invasion
      into the central nervous system.

PMID- 16453144
TI  - Optic nerve degeneration in the DBA/2NNia mouse: is the lamina cribrosa important
      in the development of glaucomatous optic neuropathy?
AB  - To study optic nerve (ON) degeneration in the DBA/2NNia (DBA) mouse, a species
      lacking a lamina cribrosa and a model for secondary angle-closure glaucoma,
      serial semi- and ultra-thin sectioning of the myelinated ON and of the ON head
      was performed and sections evaluated qualitatively and quantitatively by light
      and electron microscopy. Immunohistochemistry was performed using antibodies
      against collagen type I, III, VI, laminin, and connexin43. The major finding on
      the myelinated ON was a significant decrease in cross section area during ON
      degeneration which was paralleled by a loss of axons and an increase in
      microglia. The number of astrocytes and blood vessels did not change. The major
      findings on the ON papilla were that ON heads with only mild degeneration showed
      a pronounced focal degeneration around the central retinal artery. In more
      severely degenerated ON, newly formed bundles of collagen type VI were located
      between astrocyte processes within the ON head. In a species that has no lamina
      cribrosa, DBA mice can develop typical signs of glaucomatous optic neuropathy.
      The entrance of the central retinal vessels into the ONH seems to be a
      preferentially vulnerable region for axon loss in this mouse model. In addition,
      astrocytes in the ON head form extracellular material similar to that found in
      human glaucomatous eyes.

PMID- 16453145
TI  - Automatized assessment of 1p36-19q13 status in gliomas by interphase FISH assay
      on touch imprints of frozen tumours.
AB  - Molecular genetic analyses have demonstrated that combined losses in 1p36 and
      19q13 were associated with a good response to treatment and a higher survival
      rates in oligodendrogliomas (O). The presence of such deletions in a subset of
      mixed oligoastrocytomas (OA) also suggests that 1p-19q status may assist the
      histological classification of gliomas. Representative frozen fragments of 25
      patients with a primary grade II or III glioma [2 O, 8 astrocytic tumours (A), 15
      OA] were selected and a sensitive interphase fluorescent in situ hybridization
      (FISH) analysis was developed on serial touch preparations using two sets of
      probes. A positive detection threshold at 6% was reached by the use of both touch
      imprints and a new set of LSI 1p36/19q13 Abbott-Vysis probes. Strong and discrete
      hybridization signals of these probes facilitated the following FISH analysis;
      indeed, an automatic analysis of the hybridization patterns (Metafer 4,
      Metasystems, Althlussheim, Germany) was compared with visual counting. Both
      methods were highly correlated and combined 1p-19q losses found in five tumours
      with an oligodendroglial component (2 O, 3 OA). The automatic system allowed the
      capture and storage of hybridization patterns and the processing of several
      slides. A convenient checking of the nuclei gallery was done with direct recall
      and visual verification on the slides of nuclei with ambiguous hybridization
      patterns. The recently developed probes together with automatic counting may
      facilitate multicentric evaluation and standardization of 1p-19q assessment in
      gliomas.

PMID- 16453141
TI  - Understanding the rise of the superbug: investigation of the evolution and
      genomic variation of Staphylococcus aureus.
AB  - The bacterium Staphylococcus aureus is a common cause of human infection, and it
      is becoming increasingly virulent and resistant to antibiotics. Our understanding
      of the evolution of this species has been greatly enhanced by the recent
      sequencing of the genomes of seven strains of S. aureus. Comparative genomic
      analysis allows us to identify variation in the chromosomes and understand the
      mechanisms by which this versatile bacterium has accumulated diversity within its
      genome structure.

PMID- 16453146
TI  - Factors affecting crystal precipitation from urine in individuals with long-term
      urinary catheters colonized with urease-positive bacterial species.
AB  - Weekly urinalysis was conducted for 12 weeks on a group of 21 long-term catheter
      users with confirmed catheter encrustation and urinary tract colonization with
      urease-positive bacteria, in order to explore the cause of considerable variation
      in the severity of encrustation between sufferers. The rapidity of catheter
      blockage correlated significantly with the pH above which crystals precipitated
      from urine (the nucleation pH) but not the pH of the voided urine itself. Linear
      regression showed the nucleation pH to be significantly predicted by a
      combination of urinary calcium and magnesium concentrations, with calcium being
      the more influential variable. Reducing the rate of catheter encrustation could
      be achieved by lowering the urinary concentration of calcium and magnesium, which
      may only require catheter users to increase their fluid intake.

PMID- 16453147
TI  - The actions of the neonicotinoid imidacloprid on cholinergic neurons of
      Drosophila melanogaster.
AB  - The neonicotinoid insecticide imidacloprid is an agonist on insect nicotinic
      acetylcholine receptors (nAChRs). We utilised fura-2-based calcium imaging to
      investigate the actions of imidacloprid on cultured GFP-tagged cholinergic
      neurons from the third instar larvae of the genetic model organism Drosophila
      melanogaster. We demonstrate dose-dependent increases in intracellular calcium
      ([Ca2+]i) in cholinergic neurons upon application of imidacloprid (10 nM-100 muM)
      that are blocked by nAChR antagonists mecamylamine (10 microM) and alpha
      bungarotoxin (alpha-BTX, 1 microM). When compared to other (untagged) neurons,
      cholinergic neurons respond to lower concentrations of imidacloprid (10-100 nM)
      and exhibit larger amplitude responses to higher (1-100 microM) concentrations of
      imidacloprid. Although imidacloprid acts via nAChRs, increases in [Ca2+]i also
      involve voltage-gated calcium channels (VGCCs) in both groups of neurons. Thus,
      we demonstrate that cholinergic neurons express nAChRs that are highly sensitive
      to imidacloprid, and demonstrate a role for VGCCs in amplifying imidacloprid
      induced increases in [Ca2+]i.

PMID- 16453148
TI  - Quantification of mtDNA mixtures in forensic evidence material using
      pyrosequencing.
AB  - Analysis of mtDNA variation using Sanger sequencing does not allow accurate
      quantification of the components of mtDNA mixtures. An alternative method to
      determine the specific mixture ratios in samples displaying hetero-plasma,
      consisting of DNA contributions from several individuals, or containing
      contamination would therefore be valuable. A novel quantification system for
      mtDNA mixture analysis has been developed based on pyrosequencing technology, in
      which the linear relationship between incorporated nucleotides and released light
      allows quantification of the components of a sample. Within five polymerase chain
      reaction fragments, seven variable positions in the mtDNA control and coding
      region were evaluated using this quantification analysis. For all single
      nucleotide polymorphisms quantified in this study, a linear relationship was
      observed between the measured and expected mixture ratios. This mtDNA
      quantification assay is an easy to use, fast and accurate quantification system,
      with the ability to resolve and interpret major and minor mtDNA components in
      forensic mixture samples.

PMID- 16453149
TI  - Local thymic caspase-9 inhibition improves survival during polymicrobial sepsis
      in mice.
AB  - Caspase-9 is believed to play an essential role in sepsis-induced lymphocyte
      apoptosis. The aim of this study was therefore to evaluate its contribution
      within the caspase-dependent apoptosis pathway in a murine model of polymicrobial
      sepsis. Local injections of Z-LEHD-fmk, a specific caspase-9 inhibitor, into
      thymi of septic mice led to the complete inhibition of caspase-9, decreased
      apoptosis of resident tissue cells, and, in addition, reduced further downstream
      caspase-3 activity. In contrast to its systemic administration, only local
      injections improved the overall survival of septic mice. However, local
      injections of a pancaspase inhibitor (Z-VAD-fmk) did not improve survival,
      although caspase-3 activity was reduced to a similar degree as by the
      administration of Z-LEHD-fmk. These results indicate that local apoptosis of
      lymphatic tissue in polymicrobial sepsis is processed dependent of caspase-9 and
      suggests alternative caspase-dependent beneficial effects, which may determine a
      positive outcome.

PMID- 16453151
TI  - Tumour-expressed tissue factor inhibits cellular cytotoxicity.
AB  - AIMS: The association between tissue factor (TF) expression and increased rate of
      tumour metastasis is well established. In this study, we have examined the
      hypothesis that the expression of TF by disseminated tumour cells confers
      protection against immune recognition and cytotoxicity. MATERIALS AND METHODS: A
      hybrid EGFP-TF protein was expressed in HT29 colon carcinoma and K562 lymphoblast
      cell lines. To assess the cytotoxic activity against tumour cells over-expressing
      TF, a novel method was used, based on the direct measurement of fluorescently
      labelled HT29 or K562 target cells. RESULTS: Upon challenge with peripheral blood
      mononuclear cells (PBMC), tumour cells expressing TF partially evaded cellular
      cytotoxicity (Delta=15-40% reduction in cytotoxicity). Moreover, the influence of
      TF was not primarily dependent on its procoagulant function, although the
      inclusion of 20% (v/v) plasma did lower the rate of cytotoxicity against
      untransfected cells. However, expression of a truncated form of TF, devoid of the
      cytoplasmic domain, did not mediate any degree of inhibition of cytotoxicity,
      suggesting that the protective function of TF is principally due to this domain.
      CONCLUSIONS: We conclude that TF can promote immune evasion in tumour cells
      expressing this protein leading to increased survival and therefore metastatic
      rate in such cells.

PMID- 16453150
TI  - Expression of macrophage-derived chemokine (MDC)/CCL22 in human lung cancer.
AB  - BACKGROUND: Ligands for CXCR3 chemokines [IFN-gamma-inducible protein of 10 kD
      (IP-10/CXCL10), monokine induced by IFN-gamma (Mig/CXCL9), IFN-inducible T cell
      alpha chemoattractant (I-TAC/CXCL11)] and those for CCR4 [macrophage-derived
      chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17)]
      have been shown to play the central roles for T helper-cell recruitment into the
      tissues. To examine the role of these chemokines in tumor progression of lung
      cancer, we investigated their expression in human lung cancer tissues to
      determine the possible relationship between their expression and the prognosis of
      patients. METHODS: Total RNA was prepared from lung cancer tissues of 40 patients
      (24 adenocarcinoma and 16 squamous cell carcinoma). We measured gene expression
      levels of chemokines (IP-10, Mig, I-TAC, MDC and TARC) by real-time quantitative
      RT-PCR. RESULTS: Higher gene expression of MDC in lung cancer was significantly
      correlated with longer disease-free survival time and lower risk of recurrence
      after tumor resection. We could not find any significant relationship of IP-10,
      Mig, I-TAC and TARC gene expression with disease-free survival or lower risk of
      recurrence after surgery. CONCLUSIONS: These results suggest that increased gene
      expression of MDC in tumor tissues may be a predictive marker for improving the
      prognosis of lung cancer.

PMID- 16453152
TI  - The immunologically active site of prothymosin alpha is located at the carboxy
      terminus of the polypeptide. Evaluation of its in vitro effects in cancer
      patients.
AB  - Prothymosin alpha (proTalpha) is a 109 amino acid long polypeptide presenting
      distinct immunoenhancing activity in vitro and in vivo. Recent reports suggest
      that in apoptotic cells, proTalpha is cleaved by caspases at its carboxy(C)
      terminus generating potentially bioactive fragments. In this study, we identified
      the peptide segment of proTalpha presenting maximum immunomodulatory activity.
      Calf thymus proTalpha was trypsinised, and the five fragments produced (spanning
      residues 1-14, 21-30, 31-87, 89-102 and 103-109) were tested for their ability to
      stimulate healthy donor- and cancer patient-derived peripheral blood mononuclear
      cell (PBMC) proliferation in autologous mixed lymphocyte reaction (AMLR), natural
      killer and lymphokine-activated killer cell activity, intracellular production of
      perforin, upregulation of adhesion molecules and CD25 expression. ProTalpha(89
      102) and proTalpha(103-109) significantly fortified healthy donor-lymphocytes'
      immune responses to levels comparable to those induced by intact proTalpha. These
      effects were more pronounced in cancer patients, where peptides proTalpha(89-102)
      and proTalpha(103-109) partly, however significantly, restored the depressed AMLR
      and cytolytic ability of PBMC, by simulating the biological activity exerted by
      intact proTalpha. ProTalpha(1-14), proTalpha(21-30) and proTalpha(31-87)
      marginally upregulated lymphocyte activation. This is the first report showing
      that proTalpha's immunomodulating activity can be substituted by its C-terminal
      peptide(s). Whether generation and externalization of such immunoactive proTalpha
      fragments occurs in vivo, needs further investigation. However, if these peptides
      can trigger immune responses, they may eventually be used therapeutically to
      improve some PBMC functions of cancer patients.

PMID- 16453153
TI  - Interaction between K+ channel gate modifier hanatoxin and lipid bilayer
      membranes analyzed by molecular dynamics simulation.
AB  - Hanatoxin (HaTx) is an ellipsoidal-shaped peptide that binds to the voltage
      sensor of voltage-dependent channels. Of physicochemical interest, HaTx has a
      "ring" of charged residues around its periphery and a hydrophobic protrusion. It
      has previously been postulated that HaTx binds to and functions on the surface of
      membranes, but a recent fluorescent-quenching study has implied a fairly deep
      positioning of HaTx in the lipid bilayer membrane. We carried out numerous
      molecular dynamic simulations of HaTx1, a well-studied variant of HaTx, in fully
      hydrated phospholipid bilayers. The system reproduced the surface-binding mode of
      HaTx1, in which HaTx1 resided in the extracellular side (outer) of the
      water/membrane interface with the hydrophobic patch of HaTx1 facing the membrane
      interior. On the other hand, analyses with various parameter settings suggested
      that the surface-binding mode was unstable because of the substantial attractive
      electrostatic force between HaTx1 and the lipid head groups of the inner
      (opposite) leaflet. Compared with this electrostatic force, the energetic cost
      for membrane deformation involving meniscus formation appeared to be small. In an
      attempt to interpret the quenching data, we consider the possibility of dimpling
      (meniscus formation) that brings HaTx1 inward (only ~0.7-0.8 nm above the bilayer
      center), while accounting for the flexibility of both leaflets of the membrane
      and the long-range interaction between positively charged residues of the
      membrane-bound peptide and the polar head groups of the opposite leaflet of the
      membrane. It is suggested that molecular dynamics simulations taking into account
      the flexibility of the membrane surface is potentially useful in interpreting the
      fluorescence-quenching data.

PMID- 16453154
TI  - Efficiency of transcriptional gene silencing of GBSSI in potato depends on the
      promoter region that is used in an inverted repeat.
AB  - Transcriptional gene silencing (TGS) of the endogenous GBSSI promoter in potato
      was induced by inverted repeat constructs containing different regions of the
      GBSSI promoter. Clear differences in silencing efficiency were observed. The
      35SGBP-IR construct, containing sequences from -766 to -168 bp relative to the
      transcription initiation site (TIS), induced weak silencing effects in 57-60% of
      the transformants. Weak silencing effects were also induced by the ASP-IR
      construct harbouring allele-specific sequences covering the region from -531 to 
      330 bp relative to the TIS, but only in a low percentage (4-5.5%) of the
      transformants. These percentages are too low to distinguish effects between the
      two potato cultivars. Therefore, this approach cannot be used to induce allele
      specific TGS. Strong silencing effects were obtained in 49% of the transformants
      harbouring the full promoter inverted repeat construct. This construct contained
      sequences from -766 to +194 bp relative to the TIS. In the strongly silenced
      transformants no GBSSI mRNA could be detected by Northern blot analysis. This was
      accompanied by the accumulation of GBSSI promoter-specific small interfering
      RNAs. Methylation studies revealed that, in the weakly silenced 35SGBP-IR
      transformants, the HpaII site at -213 bp relative to the TIS was methylated.
      Apparently, methylation of this sequence does not result in strong silencing
      effects. In the full promoter transformants, both CG methylation and CNN
      methylation were detected. We show that, to obtain strong TGS, it is important to
      include sequences in the vicinity of the TIS.

PMID- 16453155
TI  - Role of 18F-FDG PET/CT in the assessment of bone involvement in newly diagnosed
      multiple myeloma: preliminary results.
AB  - PURPOSE: Multiple myeloma (MM) is a malignant B cell and plasma cell disorder
      which involves the skeleton in more than 80% of patients at diagnosis. The aim of
      this study was to compare whole-body X-ray (WBXR), MRI and (18)F-FDG PET/CT in
      patients with MM. METHODS: The study population comprised 28 newly diagnosed MM
      patients. Findings of (18)F-FDG PET/CT were compared with those of WBXR and MRI
      with regard to the number and site of lesions detected. RESULTS: Comparing (18)F
      FDG PET/CT and WBXR, it was found that in 16/28 pts (57%) (18)F-FDG PET/CT
      detected more lesions, all of which were located in the skeleton. Nine of these
      16 patients had a completely negative WBXR survey. In 12/28 pts (43%) the two
      methods yielded equivalent findings. Comparing (18)F-FDG PET/CT and MRI, it was
      found that in 7/28 pts (25%), (18)F-FDG PET/CT detected more lytic bone lesions,
      all of which were located outside the field of view of MRI (bone lesions in six
      cases and a soft tissue lesion in one). In 14/28 pts (50%), (18)F-FDG PET/CT and
      MRI detected the same number of lesions in the spine and pelvis, while in 7/28
      pts (25%) MRI detected an infiltrative pattern in the spine whereas (18)F-FDG
      PET/CT was negative. CONCLUSION: (18)F-FDG PET/CT appears to be more sensitive
      than WBXR for the detection of small lytic bone lesions, whereas it has the same
      sensitivity as MRI in detecting bone disease of the spine and pelvis. On the
      other hand, MRI may be superior to (18)F-FDG PET/CT in diagnosing an infiltrative
      pattern in the spine. Therefore, careful evaluation of MM bone disease at
      diagnosis should include both MRI of the spine and (18)F-FDG PET/CT.

PMID- 16453156
TI  - Effects of combining ethanol (EtOH) with gamma-hydroxybutyrate (GHB) on the
      discriminative stimulus, locomotor, and motor-impairing functions of GHB in mice.
AB  - RATIONALE: Gamma-hydroxybutyrate (GHB) is a drug of abuse that is often coabused
      with ethanol (EtOH) and has been implicated as a date rape agent in conjunction
      with EtOH. Much information is lacking regarding the manner in which GHB
      interacts with EtOH. OBJECTIVE: This study was designed to further characterize
      the behavioral effects of GHB alone and in combination with EtOH in male Swiss
      Webster mice. METHODS: The effects of GHB (0.1-1.0 g/kg) and EtOH (2.0-5.0 g/kg)
      alone, as well as the effects of GHB in combination with EtOH, were examined
      using an automated locomotor activity procedure, a functional observational
      battery (FOB) and a GHB drug discrimination procedure. RESULTS: GHB decreased,
      whereas EtOH had little effect on locomotor activity. In the FOB, EtOH dose
      dependently decreased activity in combination with 0.3 g/kg GHB. Alone, each drug
      had little effect on the righting reflex, but combining ineffective doses of GHB
      and EtOH significantly impaired righting. GHB and EtOH decreased forelimb grip
      strength. Combinations of ineffective doses of GHB and EtOH decreased forelimb
      grip strength when given together. GHB and EtOH impaired inverted screen
      performance, and EtOH increased the impairing effects of low, but not high, doses
      of GHB. GHB and EtOH increased hind limb splay, and EtOH increased the effects of
      0.1 and 0.3 g/kg GHB on splay. GHB and EtOH decreased body temperature, and EtOH
      augmented the temperature-decreasing effects of GHB. EtOH produced less than 50%
      GHB-like discriminative stimulus effects, and GHB failed to alter the GHB-like
      discriminative stimulus effects of EtOH. CONCLUSIONS: Overall, EtOH increased the
      effects of GHB on several gross measures of behavior and only partially
      occasioned the discriminative stimulus properties of GHB.

PMID- 16453158
TI  - Titin/connectin-based modulation of the Frank-Starling mechanism of the heart.
AB  - The basis of the Frank-Starling mechanism of the heart is the increase in active
      force when muscle is stretched. Various findings have shown that muscle length,
      i.e., sarcomere length (SL), modulates activation of cardiac myofilaments at a
      given concentration of Ca2+ ([Ca2+]). This augmented Ca2+ activation with SL,
      commonly known as "length-dependent activation", is manifested as the leftward
      shift of the force-pCa (= -log [Ca2+]) relation as well as by the increase in
      maximal Ca2+ -activated force. Despite the numerous studies that have been
      undertaken, the molecular mechanism(s) of length-dependent activation is (are)
      still not fully understood. The giant sarcomere protein titin/connectin is the
      largest protein known to date. Titin/connectin is responsible for most passive
      force in vertebrate striated muscle and also functions as a molecular scaffold
      during myofibrillogenesis. Recent studies suggest that titin/connectin plays an
      important role in length-dependent activation by sensing stretch and promoting
      actomyosin interaction. Here we review and extend this previous work and focus on
      the mechanism by which titin/connectin might modulate actomyosin interaction.

PMID- 16453159
TI  - Connecting filament mechanics in the relaxed sarcomere.
AB  - By examining the mechanical properties of single unactivated myofibrils it has
      been shown that shortening and stretching of sarcomeres occurs in stepwise
      fashion, and that steps are seen also in the relaxed state (Yang et al. (1998)
      Biophys J 74: 1473-1483; Blyakhman et al. (2001) Biophys J 81: 1093-1100;
      Nagornyak et al. (2004) J. Muscle. Res. Cell Motil. 25: 37-43). The latter are
      inevitably associated with connecting filaments. Here, we carried out
      measurements on single myofibrils from rabbit psoas muscle to investigate steps
      in unactivated specimens in more detail. Myofibrils were stretched and released
      in ramp-like fashion. For the single sarcomere the time course of length change
      was consistently stepwise. We found that in the unactivated myofibrils, step size
      depended on initial sarcomere length, diminishing progressively with increase of
      initial sarcomere length, whereas in the case of activated sarcomeres, step size
      was consistently 2.7 nm.

PMID- 16453157
TI  - Back on track - on the role of the microtubule for kinesin motility and cellular
      function.
AB  - The evolution of cytoskeletal filaments (actin- and intermediate-filaments, and
      the microtubules) and their associated motor- and non-motor-proteins has enabled
      the eukaryotic cell to achieve complex organizational and structural tasks. This
      ability to control cellular transport processes and structures allowed for the
      development of such complex cellular organelles like cilia or flagella in single
      cell organisms and made possible the development and differentiation of multi
      cellular organisms with highly specialized, polarized cells. Also, the faithful
      segregation of large amounts of genetic information during cell division relies
      crucially on the reorganization and control of the cytoskeleton, making the
      cytoskeleton a key prerequisite for the development of highly complex genomes.
      Therefore, it is not surprising that the eukaryotic cell continuously invests
      considerable resources in the establishment, maintenance, modification and
      rearrangement of the cytoskeletal filaments and the regulation of its interaction
      with accessory proteins. Here we review the literature on the interaction between
      microtubules and motor-proteins of the kinesin-family. Our particular interest is
      the role of the microtubule in the regulation of kinesin motility and cellular
      function. After an introduction of the kinesin-microtubule interaction we focus
      on two interrelated aspects: (1) the active allosteric participation of the
      microtubule during the interaction with kinesins in general and (2) the possible
      regulatory role of post-translational modifications of the microtubule in the
      kinesin-microtubule interaction.

PMID- 16453160
TI  - Twitchin purified from molluscan catch muscles regulates interactions between
      actin and myosin filaments at rest in a phosphorylation-dependent manner.
AB  - Twitchin, also called mini-titin, is structurally related to the giant elastic
      protein connectin/titin, and has been found in not only striated but also smooth
      muscles of bivalves. Many bivalve smooth muscles such as byssus retractor muscles
      and the opaque part of adductor muscles are known as catch muscles that can
      maintain high passive tension with little expenditure of energy after they have
      actively contracted. Twitchin is phosphorylated when this high-tension state
      (catch state) ceases. Our recent studies revealed that the catch tension is due
      to interactions between thick and thin filaments in the presence of MgATP at low
      free Ca2+ concentrations, which can be visualized in vitro under a light
      microscope (Yamada et al., 2001 Proc Natl Acad Sci USA 98: 6635-6640). We also
      found that twitchin is essential for the interactions of the catch state in
      mussel (Mytilus galloprovincialis) catch muscles. In the presence of twitchin,
      actin filaments bound to purified myosin filaments when twitchin was
      dephosphorylated by Ser/Thr protein phosphatase 2B, while they did not when it
      was phosphorylated by cAMP-dependent protein kinase. In the current study we
      demonstrate the same essential components of the catch state for another bivalve
      that exhibits catch, i.e., Japanese oyster (Crassostrea gigas).

PMID- 16453161
TI  - Twitchin as a regulator of catch contraction in molluscan smooth muscle.
AB  - Molluscan catch muscle can maintain tension for a long time with little energy
      consumption. This unique phenomenon is regulated by phosphorylation and
      dephosphorylation of twitchin, a member of the titin/connectin family. The catch
      state is induced by a decrease of intracellular Ca2+ after the active contraction
      and is terminated by the phosphorylation of twitchin by the cAMP-dependent
      protein kinase (PKA). Twitchin, from the well-known catch muscle, the anterior
      byssus retractor muscle (ABRM) of the mollusc Mytilus, incorporates three
      phosphates into two major sites D1 and D2, and some minor sites.
      Dephosphorylation is required for re-entering the catch state. Myosin, actin and
      twitchin are essential players in the mechanism responsible for catch during
      which force is maintained while myosin cross-bridge cycling is very slow.
      Dephosphorylation of twitchin allows it to bind to F-actin, whereas
      phosphorylation decreases the affinity of the two proteins. Twitchin has been
      also been shown to be a thick filament-binding protein. These findings raise the
      possibility that twitchin regulates the myosin cross-bridge cycle and force
      output by interacting with both actin and myosin resulting in a structure that
      connects thick and thin filaments in a phosphorylation-dependent manner.

PMID- 16453162
TI  - Molecular and biochemical characterization of kettin in Caenorhabditis elegans.
AB  - Kettin is a unique member of the connectin/titin family of muscle elastic
      proteins, which has repetitive immunoglobulin-like domains that are separated by
      weakly conserved linker sequences. In striated muscles of insects and crayfish,
      kettin binds to actin filaments and localizes to the Z-disc and its adjacent
      region in the I-band. Recent sequence analysis of invertebrate connectin/titin
      (also known as SLS proteins) has revealed that kettin is a splice variant of
      connectin/titin. In contrast, in the nematode Caenorhabditis elegans, the kettin
      gene is independent of the genes for other connectin/titin-related proteins.
      Immunofluorescent localization of kettin shows that it localizes to the I-bands
      in the obliquely striated body wall muscle. Therefore, C. elegans is an
      attractive model system to study specific functions of kettin in muscle cells.

PMID- 16453163
TI  - Titin/connectin-related proteins in C. elegans: a review and new findings.

PMID- 16453166
TI  - Predominance of char sorption over substrate concentration and soil pH in
      influencing biodegradation of benzonitrile.
AB  - Incomplete combustion of field crop residues results in the production of char, a
      material rich in charcoal-type substances. Consequently, char is an effective
      adsorbent of organic compounds and when incorporated into soil may adsorb soil
      applied pesticides, thereby altering their susceptibility to biodegradation. We
      investigated the relative importance of char, soil pH and initial substrate
      concentration in biodegradation of pesticides in soils by measuring the
      biodegradation of benzonitrile in soil as a function of soil char content (0% and
      1% by weight), initial benzonitrile concentration (0.1, 1.06, and 10.2 mg l(-1))
      and soil pH (5.2, 6.9 and 8.5). Preliminary experiments revealed that wheat straw
      char had a much greater benzonitrile sorption capacity than did soil to which the
      char was added. The extent of benzonitrile degradation decreased as initial
      benzonitrile concentration increased in both buffer solution and soil slurry. In
      contrast, the degradation increased as initial benzonitrile concentration
      increased in char-amended slurry. In un-amended soil slurry, the benzonitrile
      degradation was lower at pH 5.2 than at pH 6.9 or 8.5, but in char-amended soil
      slurry the degradation was not affected by pH, again presumably due to adsorption
      of benzonitrile by the char. Adsorption by soil char appears to be more important
      than either initial substrate concentration or soil pH in controlling
      benzonitrile degradation in char-amended soil slurry. The presence of crop
      residue-derived chars may alter pesticide degradation patterns normally observed
      in soils and thus significantly affect their environmental fate.

PMID- 16453164
TI  - Possible functions of p94 in connectin-mediated signaling pathways in skeletal
      muscle cells.
AB  - Calpains are intracellular Ca2+ -requiring 'modulator proteases', which modulate
      cellular functions by limited and specific proteolysis. p94/calpain3, a skeletal
      muscle specific calpain, has been one of the representative calpain species which
      indicates physiological importance of calpain proteolytic system; a defect of
      proteolytic activity of p94 causes limb girdle muscular dystrophy type2A (LGMD2A,
      also called 'calpainopathy'). Immunohistochemical studies on myofibrils showed
      that p94 localizes at the Z- and N2-line regions of sarcomeres. It was also
      identified by the yeast two hybrid studies that p94 binds to the N2A and M-line
      regions of connectin. Furthermore, genetic studies indicate that p94 is
      indispensable for skeletal muscles, although its precise functions are still
      unclear. Interestingly, connectin provides sarcomere not only with elasticity but
      also with binding sites to various multi-functional proteins such as muscle
      ankyrin repeat proteins (MARPs), muscle RING finger proteins (MURFs), titin
      capping protein (T-cap/telethonin), sarcomeric-alpha-actinin, p94 etc. Binding
      sites for these proteins are not randomly placed along connectin but rather
      accumulated in the Z-, N2-, and/or M-line regions, indicating the existence of
      'signal complexes' unique to each regions. The concept of these complexes are
      strongly supported by the facts that mutations of connectin or its binding
      proteins in these regions severely perturb muscle functions, as in the case of
      LGMD2A caused by mutations in the p94 gene. Therefore, it is hypothesized that
      the 'signal complexes' in the Z-, N2-, and M-lines modulate muscle cell
      homeostasis by transducing signals of external stimulations/stresses to trigger
      appropriate response at various different cellular events such as protein
      modification and gene expressions. In this article, we performed detailed
      immunohistochemical analyses of p94 on isolated single myofibers. Together with
      recent findings about p94, it is suggested that sarcomeric localization of p94,
      especially its M-line localization, is affected by the combination of cellular
      contexts such as contractile status of myofibrils, fiber type compositions,
      sarcomeric maturation, and the composition of the 'signal complexes' in each
      region.

PMID- 16453167
TI  - Impact of anaerobic and aerobic processes on polychlorobiphenyl removal in
      contaminated sewage sludge.
AB  - Aerobic and anaerobic biodegradation of six priority PCBs was investigated in
      continuous stirred tank reactors fed with naturally contaminated sewage sludge.
      Anaerobic and aerobic abiotic losses were higher for the lightly chlorinated PCBs
      but remained for all PCBs below 20%. Under strict methanogenic conditions, PCB
      removals were about 40% whatever PCB molecular weight or their degree of
      chlorination. However, considering abiotic losses, the heaviest PCBs were more
      efficiently anaerobically biodegraded probably because of higher dechlorination
      rates. The aerating sludge process enhanced removal of the lightest chlorinated
      PCBs from 40% up to 100%, while removal rates of the heaviest PCBs remained
      around 40%. Although the mesophilic aerobic process exhibits better removal
      efficiencies because of operating conditions, the results suggest that PCB
      biodegradation was strongly limited by their bioavailability in naturally
      contaminated sludge, under both redox conditions. Indeed, since PCB removal was
      closely linked to the solid reduction rates, PCB bioavailability was likely the
      limiting factor for biodegradation. As a consequence, the raw PCB concentrations
      (in mg kg(-1) (dry weight)) which are concerned by legislative procedures did not
      decrease sufficiently in both processes to reach a limit value fulfilling the
      current French/European regulation about PCB contents in sewage sludge before
      spreading on agricultural land.

PMID- 16453168
TI  - Factors affecting nitrous oxide production: a comparison of biological nitrogen
      removal processes with partial and complete nitrification.
AB  - Nitrous oxide (N(2)O) emission from biological nitrogen removal (BNR) processes
      has recently received more research attention. In this study, two lab-scale BNR
      systems were used to investigate the effects of various operating parameters
      including the carbon to nitrogen (C/N) ratio, ammonia loading, and the hydraulic
      retention time on N(2)O production. The first system was operated in a
      conventional BNR mode known as the Ludzack-Ettinger (LE) process, consisting of
      complete denitrification and nitrification reactors, while the second one was
      operated in a shortcut BNR (SBNR) mode employing partial nitrification and
      shortcut denitrification, which requires less oxygen and carbon sources. As the
      C/N ratio was decreased, a significant increase in N(2)O production was observed
      only in the anoxic reactor of the LE process, indicating that N(2)O was released
      as an intermediate of the denitrification reaction under the carbon-limited
      condition. However, the SBNR process did not produce significant N(2)O even at
      the lowest C/N ratio of 0.5. When the SBNR process was subjected to increasing
      concentrations of ammonia, N(2)O production from the aerobic reactor was rapidly
      increased. Furthermore, the increasing production of N(2)O was observed mostly in
      the aerobic reactor of the SBNR process with a decline in hydraulic retention
      time. These experimental findings indicated that the increase in N(2)O production
      was closely related to the accumulation of free ammonia, which was caused by an
      abrupt increase of the ammonium loading. Consequently, the partial nitrification
      was more susceptible to shock loading conditions, resulting in a high production
      of N(2)O, although the SBNR process was more efficient with respect to nitrogen
      removals as well as carbon and oxygen requirements.

PMID- 16453169
TI  - Degradation of fumonisin B1 by a bacterial strain isolated from soil.
AB  - A mixed microbial culture degrading fumonisin B l was obtained from soil samples
      using an enrichment culture procedure. A bacterial isolate from the enrichment
      culture (strain NCB 1492) degraded fumonisin B1 after incubation for 3 h, as
      indicated by TLC and HPLC analysis. On the basis of the sequence analysis of 16S
      rDNA, strain NCB 1492 was related to the Delftia/Comamonas group. Thin-layer
      chromatographic analysis indicated the presence of metabolites in the NCB 1492
      culture filtrates after degradation of fumonisin B1 supplied as sole carbon and
      nitrogen source in phosphate buffer. Four metabolites were identified by mass
      spectrometry analysis.

PMID- 16453170
TI  - Inhibition of biogas production by alkyl benzene sulfonates (LAS) in a screening
      test for anaerobic biodegradability.
AB  - The effect of the inoculum source on the digestion of linear alkylbenzene
      sulfonates (LAS) under anaerobic conditions has been investigated. The potential
      for primary and ultimate LAS biodegradation of anaerobic sludge samples obtained
      from wastewater treatment plants (WWTPs) of different geographical locations was
      studied applying a batch test system. It was found that only 4-22% of the LAS
      added to the batch anaerobic digesters was primarily transformed suggesting a
      poor primary degradation of the LAS molecule in anaerobic discontinuous systems.
      Regarding ultimate biodegradation, the addition of LAS to the batch anaerobic
      digesters caused a reduction on the extent of biogas production. Significant
      differences in the inhibition extent of the biogas production were observed (4
      26%) depending on the sludge used as inoculum. Effect of the surfactant on the
      anaerobic microorganisms was correlated with its concentration in the aqueous
      phase. Sorption of LAS on anaerobic sludge affects its toxicity by depletion of
      the available fraction of the surfactant. LAS content on sludge was related to
      the total amount of calcium and magnesium extractable ions. The presence of
      divalent cations promote the association of LAS with anaerobic sludge reducing
      its bioavailability and the extent of its inhibitory effect on the biogas
      production.

PMID- 16453171
TI  - Phenol degradation by immobilized cells of Arthrobacter citreus.
AB  - An aerobic microorganism with an ability to utilize phenol as carbon and energy
      source was isolated from a hydrocarbon contamination site by employing selective
      enrichment culture technique. The isolate was identified as Arthrobacter citreus
      based on morphological, physiological and biochemical tests. This mesophilic
      organism showed optimal growth at 25 degrees C and at pH of 7.0. The phenol
      utilization studies with Arthrobacter citreus showed that the complete
      assimilation occurred in 24 hours. The organism metabolized phenol up to 22 mM
      concentrations whereas higher levels were inhibitory. Thin layer chromatography,
      UV spectral and enzyme analysis were suggestive of catechol, as a key
      intermediate of phenol metabolism. The enzyme activities of phenol hydroxylase
      and catechol 2,3-dioxygenase in cell free extracts of Arthrobacter citreus were
      indicative of operation of a meta-cleavage pathway for phenol degradation. The
      organism had additional ability to degrade catechol, cresols and naphthol. The
      degradation rates of phenol by alginate and agar immobilized cells in batch
      fermentations showed continuous phenol metabolism for a period of eight days.

PMID- 16453172
TI  - Treatment of groundwater contaminated with PAHs, gasoline hydrocarbons, and
      methyl tert-butyl ether in a laboratory biomass-retaining bioreactor.
AB  - In this study, we investigated the treatability of co-mingled groundwater
      contaminated with polycyclic aromatic hydrocarbons (PAHs), gasoline hydrocarbons,
      and methyl tert-butyl ether (MtBE) using an ex-situ aerobic biotreatment system.
      The PAHs of interest were naphthalene, methyl-naphthalene, acenaphthene,
      acenaphthylene, and carbazole. The gasoline hydrocarbons included benzene,
      toluene, ethyl benzene, and p-xylene (BTEX). Two porous pot reactors were
      operated for a period of 10 months under the same influent contaminant
      concentrations. The contaminated groundwater was introduced into the reactors at
      a flow rate of 4 and 9 l/day, resulting in a hydraulic retention time (HRT) of 32
      and 15 h, respectively. In both reactors, high removal efficiencies were achieved
      for the PAHs (>99%), BTEX and MtBE (>99.7%). All the PAHs of interest and the
      four BTEX compounds were detected at concentrations less than 1 mug/l throughout
      the study duration. Effluent MtBE from both reactors was observed at higher
      levels; nevertheless, its concentration was lower than the 5 mug/l Drinking Water
      Advisory for MtBE implemented in California.

PMID- 16453173
TI  - Biodegradation of petroleum hydrocarbons in seawater at low temperatures (0-5
      degrees C) and bacterial communities associated with degradation.
AB  - In this study biodegradation of hydrocarbons in thin oil films was investigated
      in seawater at low temperatures, 0 and 5 degrees C. Heterotrophic (HM) or oil
      degrading (ODM) microorganisms enriched at the two temperatures showed 16S rRNA
      sequence similarities to several bacteria of Arctic or Antarctic origin.
      Biodegradation experiments were conducted with a crude mineral oil immobilized as
      thin films on hydrophobic Fluortex adsorbents in nutrient-enriched or sterile
      seawater. Chemical and respirometric analysis of hydrocarbon depletion showed
      that naphthalene and other small aromatic hydrocarbons (HCs) were primarily
      biodegraded after dissolution to the water phase, while biodegradation of larger
      polyaromatic hydrocarbons (PAH) and C(10)-C(36) n-alkanes, including n
      hexadecane, was associated primarily with the oil films. Biodegradation of PAH
      and n-alkanes was significant at both 0 and 5 degrees C, but was decreased for
      several compounds at the lower temperature. n-Hexadecane biodegradation at the
      two temperatures was comparable at the end of the experiments, but was delayed at
      0 degree C. Investigations of bacterial communities in seawater and on adsorbents
      by PCR amplification of 16S rRNA gene fragments and DGGE analysis indicated that
      predominant bacteria in the seawater gradually adhered to the oil-coated
      adsorbents during biodegradation at both temperatures. Sequence analysis of most
      DGGE bands aligned to members of the phyla Proteobacteria (Gammaproteobacteria)
      or Bacteroidetes. Most sequences from experiments at 0 degree C revealed
      affiliations to members of Arctic or Antarctic consortia, while no such homology
      was detected for sequences from degradation experiment run at 5 degrees C. In
      conclusion, marine microbial communities from cold seawater have potentials for
      oil film HC degradation at temperatures < or =5 degrees C, and psychrotrophic or
      psychrophilic bacteria may play an important role during oil HC biodegradation in
      seawater close to freezing point.

PMID- 16453174
TI  - Bioaugmentation of bromoamine acid degradation with Sphingomonas xenophaga QYY
      and DNA fingerprint analysis of augmented systems.
AB  - One high-effective bromoamine acid (1-amino-4-bromoanthraquinone-2-sulfonic acid,
      BAA) degrading strain was isolated previously with the ability to use BAA as sole
      source of carbon and nitrogen. It was identified as Sphingomonas xenophaga QYY by
      16S rDNA sequence analysis and physio-biochemical tests. In this study,
      bioaugmentation of BAA degradation with suspended and immobilized cells of strain
      QYY was investigated. The optimal degradation conditions were as follows:
      temperature 30 degrees C, pH 6.0-7.0, 150 rev min(-1) and the immobilized cells
      maintained degradation activity to BAA after 60 days storage at 4 degrees C. The
      structure of BAA was evidently changed according to the analysis of total organic
      carbon removal of BAA (about 50%) and the UV-VIS spectra changes during the
      biodegradation. Bioaugmented systems exhibited stronger abilities degrading BAA
      than the non-bioaugmented control ones. And microbial community dynamics of
      augmented systems was revealed by amplified ribosomal DNA restriction analysis
      (ARDRA), a modern DNA fingerprint technique. The results indicated that the
      microbial community dynamics was substantially changed throughout the
      augmentation process. This study suggests that it is feasible and potentially
      useful to enhance BAA degradation using bioaugmentation with the immobilized
      cells of BAA-degrading bacterium.

PMID- 16453175
TI  - Enzyme activities and chemical changes in wet olive cake after treatment with
      Pleurotus ostreatus or Eisenia fetida.
AB  - A laboratory experiment was conducted to evaluate the enzyme activities and
      chemical changes recorded in a recalcitrant phenolic-rich waste after treatment
      with Pleurotus ostreatus or Eisenia fetida. The waste used was wet olive cake
      (alperujo in Spanish), a waste produced in huge amounts by the olive oil
      industry. Both P. ostreatus and E. fetida were very effective in removing
      phenolic compounds, the initial concentration in the wet olive cake being reduced
      in both cases by around 90%. Laccase and manganese peroxidase activities were
      measured in the growth medium of P. ostreatus, and catechol 2,3 dioxygenase
      activity was only detected in the waste treated with Eisenia; these could be the
      main factors responsible for the oxidation of phenolic compounds. Increases of
      dehydrogenase and beta-glucosidase activities were detected in the degraded wet
      olive cake by fungi or earthworms. In comparison with the natural wet olive cake,
      the degraded products had lower total organic carbon and humic acid contents but
      were rich in nitrogen and other nutrients, having lower C:N ratios. In addition,
      the toxicity of the wet olive cake against the seeds of Lepidium sativum
      significantly decreased after degradation. The low toxicity as well as moderate
      stability and maturity recorded in the wet olive cake treated with P. ostreatus
      or E. fetida imply that these products could be used as soil amendments.

PMID- 16453176
TI  - Phosphorylation of caldesmon during smooth muscle contraction and cell migration
      or proliferation.
AB  - The actin-binding protein caldesmon (CaD) exists both in smooth muscle (the heavy
      isoform, h-CaD) and non-muscle cells (the light isoform, l-CaD). In smooth
      muscles h-CaD binds to myosin and actin simultaneously and modulates the
      actomyosin interaction. In non-muscle cells l-CaD binds to actin and stabilizes
      the actin stress fibers; it may also mediate the interaction between actin and
      non-muscle myosins. Both h- and l-CaD are phosphorylated in vivo upon
      stimulation. The major phosphorylation sites of h-CaD when activated by phorbol
      ester are the Erk-specific sites, modification of which is attenuated by the MEK
      inhibitor PD98059. The same sites in l-CaD are also phosphorylated when cells are
      stimulated to migrate, whereas in dividing cells l-CaD is phosphorylated more
      extensively, presumably by cdc2 kinase. Both Erk and cdc2 are members of the MAPK
      family. Thus it appears that CaD is a downstream effector of the Ras signaling
      pathways. Significantly, the phosphorylatable serine residues shared by both CaD
      isoforms are in the C-terminal region that also contains the actin-binding sites.
      Biochemical and structural studies indicated that phosphorylation of CaD at the
      Erk sites is accompanied by a conformational change that partially dissociates
      CaD from actin. Such a structural change in h-CaD exposes the myosin-binding
      sites on the actin surface and allows actomyosin interactions in smooth muscles.
      In the case of non-muscle cells, the change in l-CaD weakens the stability of the
      actin filament and facilitates its disassembly. Indeed, the level of l-CaD
      modification correlates very well in a reciprocal manner with the level of actin
      stress fibers. Since both cell migration and cell division require dynamic
      remodeling of actin cytoskeleton that leads to cell shape changes,
      phosphorylation of CaD may therefore serve as a plausible means to regulate these
      processes. Thus CaD not only links the smooth muscle contractility and non-muscle
      motility, but also provides a common mechanism for the regulation of cell
      migration and cell proliferation.

PMID- 16453177
TI  - Identification of differentially expressed genes in clear cell renal cell
      carcinoma by analysis of full-length enriched cDNA library.
AB  - Renal cell carcinoma (RCC) is the most common malignancy in adult kidney, and
      accounts for 3% of malignancies worldwide with increasing incidence. Clear cell
      RCC (ccRCC) is the major type in RCC. Resection by surgery is the main treatment
      because the response of ccRCC to traditional therapies is very poor. To identify
      the tumor-associated genes for better understanding the molecular mechanism of
      ccRCC, the full-length enriched cDNA libraries of ccRCC and normal kidney tissues
      were constructed by the oligo-capping method. Nucleotide sequences of the cDNA
      libraries of ccRCC and normal kidney tissues were sequenced. From the sequence
      analysis of 19,425 and 12,400 clones of ccRCC and normal kidney tissues, 4356 and
      3055 genes were identified, respectively. By comparing the gene-expression
      patterns of ccRCC and normal tissues, the up- or down-regulated genes were
      identified. Among these identified genes, the differential expression of annexin
      A2 and argininosuccinate synthetase genes were further confirmed by quantitative
      real-time PCR and Western blot analysis.

PMID- 16453178
TI  - Mutations on CaENO1 in Candida albicans inhibit cell growth in the presence of
      glucose.
AB  - Enolase (2-phospho-D-glycerate hydrolase) is an enzymatic component of the
      glycolytic pathway and is conserved through evolution. The TR-CaENO1/Caeno1
      stain, of which the expression of CaENO1 is under control of the tetracycline
      regulatable (TR) expression system, is utilized for elucidating the functions of
      CaENO1 in Candida albicans. As expected, there was no detectable CaENO1 mRNA when
      the TR-CaENO1/Caeno1 cells grew on media containing doxycycline repressing the
      expression of TR-CaENO1.The TR-CaENO1/Caeno1 cells were arrested in media
      containing doxycycline in the presence of glucose but not in non-fermentable
      carbon sources, such as glycerol. Furthermore, the TR-CaENO1/Caeno1 cells were
      also arrested in media containing 4% serum. In this study, we have showed that
      CaENO1 is required for the cell growth of C. albicans in the presence of glucose.
      Our findings may help us to design new and more effective antifungal agents for
      preventing and treating bloodstream fungal infections by blocking the function(s)
      of enolases.

PMID- 16453179
TI  - Antimuscarinic actions of antihistamines on the heart.
AB  - Antimuscarinic side-effects, which include dry mouth, tachycardia, thickening of
      mucus possibly sedation, of the antihistamines limited the usefulness of these
      drugs. The advent of newer agents has reduced the sedative effect of the
      antihistamine. The data presented here show that one of the newest
      antihistamines, desloratadine, and a first generation drug, diphenhydramine, are
      both competitive inhibitors of muscarinic receptor mediated slowing of the heart
      as measured using a Langendorff preparation. Both agents have apparent sub
      micromolar affinities for the muscarinic receptor. Two other agents, cetirizine
      and fexofenadine, do not interact with muscarinic receptors in the heart at the
      concentrations used in this study. Structural similarities of the drugs suggest
      that substitution of a group with a high dipole moment or charge on the side
      chain nitrogen decreases the binding with muscarinic receptors. We conclude that
      of the compounds tested fexofenadine and cetirizine have little or no interaction
      with muscarinic receptors.

PMID- 16453181
TI  - Human herpesvirus-8 in Kaposi's sarcoma of the conjunctiva in a patient with
      AIDS.
AB  - PURPOSE: To demonstrate human herpesvirus-8 (HHV-8) in Kaposi's sarcoma (KS) of
      the conjunctiva in a patient with acquired immunodeficiency syndrome (AIDS).
      METHODS: Clinical observation, pathologic findings of conjunctival specimens,
      immunohistochemical staining for HHV-8-specific antigen, polymerase chain
      reaction (PCR) analysis of HHV-8 DNA, and detection of specific antibody in
      patient's serum at appropriate times. RESULTS: In the conjunctival specimen,
      swollen endothelial-like cells were found with slit-like vessels. CD 31-positive
      cells were noted on the inner surface of the slit-like vessels, and HHV-8 latency
      associated nuclear antigen was detected. The presence of HHV-8 DNA was
      demonstrated by PCR. Anti-HHV-8 antibody was found in the patient's serum.
      CONCLUSIONS: This is the first case report in the ophthalmology literature that
      provides histological, DNA, and serological evidence that HHV-8 is involved in
      the pathogenesis of conjunctival KS.

PMID- 16453180
TI  - Expression of beta defensins in ocular surface tissue of experimentally developed
      allergic conjunctivitis mouse model.
AB  - PURPOSE: To investigate the expression of beta-defensin in the ocular surface of
      a mouse experimental allergic conjunctivitis (EAC) model. METHODS: Mouse beta
      defensin (mBD)-1 and -2 mRNA expressed in conjunctival tissue of both the EAC and
      the control group were analyzed by real-time reverse transcriptase-polymerase
      chain reaction (RT-PCR) analysis. mBD-1 and mBD-2 mRNA expressed in cornea,
      limbus, and conjunctival epithelium of the EAC and the control group were also
      analyzed using a laser-assisted microdissection technique and the RT-PCR method.
      RESULTS: There was no significant difference in the amount of mBD-1 between the
      EAC and the control group. However, the EAC group had significantly less mBD-2
      (0.23 +/- 0.15 x 10(4) copy/microl) than the control group (3.61 +/- 4.87 x 10(4)
      copy/microl) (P < 0.01, Mann-Whitney U test). mBD-1 mRNA was positive for all
      examined tissue in both groups. The expression of mBD-2 mRNA in the EAC group was
      definitely positive for the corneal and conjunctival epithelium and negative for
      the limbus. CONCLUSION: mBD-2 mRNA was expressed significantly less in the EAC
      model than in the control. Analysis by site in the ocular surface tissue revealed
      that this reduction was caused by the diminished expression of mBD-2 in the
      limbus.

PMID- 16453183
TI  - Correlation between individual differences in intraocular pressure reduction and
      outflow facility due to latanoprost in normal-tension glaucoma patients.
AB  - PURPOSE: The amount of intraocular pressure (IOP) reduction achieved by the use
      of latanoprost eyedrops varies among patients, and there are even nonresponders.
      This report examines whether there is any correlation between the amount of
      individual variability in IOP reduction and the uveoscleral outflow facility
      after latanoprost eyedrop instillation in normal-tension glaucoma patients.
      METHODS: Sixteen normal-tension glaucoma patients (mean age, 56.4 years) were
      enrolled in the study to investigate the relationship between the amount of IOP
      reduction and outflow facility. Before treatment, subjects underwent circadian
      IOP measurement and then tonography, and the outflow facility was calculated.
      Subsequently, patients began treatment once daily with latanoprost instillation
      in one eye. After 4 weeks of daily latanoprost treatment, circadian IOP was
      measured again. RESULTS: Mean pretreatment outflow facility was 0.23 +/- 0.05
      microl/min per mmHg. On average, latanoprost instillation decreased IOP by 2.8
      mmHg, but the reduction varied among individuals from -0.3 mmHg to 5.8 mmHg. No
      significant correlation was noted between the outflow facility and the IOP
      decline associated with latanoprost. CONCLUSION: Because there was no significant
      correlation between individual IOP reduction by latanoprost and outflow facility,
      the differences in substantial change in uveoscleral outflow after latanoprost
      administration may be one explanation for the individual variation in IOP
      reduction after treatment with this drug.

PMID- 16453182
TI  - Evaluation of optical function using a new point spread function analysis system
      in cataractous and pseudophakic eyes: preliminary results.
AB  - PURPOSE: To evaluate optical function in cataractous and pseudophakic eyes using
      the new point spread function (PSF) analysis system in a clinical setting.
      METHODS: We applied this new analysis system in the study of two cataractous eyes
      and one pseudophakic eye of two patients. Using a PSF analyzer, double-pass PSF
      was measured directly for each subject, and the single-pass modulation transfer
      function (MTF) and single-pass PSF were calculated. The simulated retinal images
      of various sizes of Landolt's rings and their contrast characteristics were also
      calculated by the PSF analyzer. RESULTS: The MTF and the contrast of the
      simulated retinal images degraded in cataractous eyes were compared with data for
      normal eyes; the degradation pattern depended on the opacification pattern. The
      MTF and the contrast of the simulated retinal images in the pseudophakic eye
      improved significantly compared with the cataractous eyes, although both values
      were lower in the pseudophakic eye than in young normal eyes. CONCLUSIONS: Our
      data showed degradation of optical function in cataractous and pseudophakic eyes
      in comparison with optical function in young normal eyes. If further
      accumulations of PSF data are made, it may be possible to establish an objective
      standard by which to measure the progression of cataract, as well as an objective
      indication for treatment in the future.

PMID- 16453184
TI  - Tracing method in the assessment of retinal capillary blood flow velocity by
      fluorescein angiography with scanning laser ophthalmoscope.
AB  - PURPOSE: To evaluate the feasibility of a new method (the tracing method) for
      measuring perifoveal capillary blood flow velocity (BFV). METHODS: The BFV in the
      perifoveal capillaries was measured in 12 eyes of healthy subjects and 12 eyes of
      patients with clinically significant macular edema (CSME) by fluorescein
      angiography using a scanning laser ophthalmoscope by either the tracing method or
      the conventional method. A randomized crossover design was employed to assign the
      subjects to each method. RESULTS: The number of capillaries recognized by the
      tracing method in healthy subjects and in patients with CSME was significantly
      higher than that recognized with the conventional method (P = 0.0134 and P =
      0.0108, respectively). The number of fluorescent dots detected by the tracing
      method in healthy subjects and in patients with CSME was also significantly
      higher than that detected with the conventional method (P = 0.0002 and P =
      0.0137, respectively). Accurate detection of the movement of fluorescent dots and
      analysis of BFV were possible with the tracing method. The BFV varied within each
      perifoveal capillary, and the mean BFV also varied according to capillary
      location in the macula. CONCLUSION: The new tracing method is useful for
      analyzing the retinal capillary BFV in healthy subjects and in patients with
      CSME.

PMID- 16453185
TI  - Comparison of the additive effects of nipradilol and carteolol to latanoprost in
      open-angle glaucoma.
AB  - PURPOSE: To compare the effects of nipradilol and carteolol on intraocular
      pressure (IOP) when added to latanoprost treatment for glaucoma patients.
      METHODS: Fifty patients with primary open-angle glaucoma were treated with
      latanoprost 0.005% once daily for 3 months. Then they were assigned to one of two
      groups randomly. One group received nipradilol 0.25% twice daily (nipradilol
      preceding group; n = 25), and the other carteolol hydrochloride 2% twice daily
      (carteolol preceding group; n = 25), for 3 months in addition to latanoprost.
      Then, nipradilol and carteolol were switched, and the subjects were treated for 3
      more months. One eye was selected randomly for analysis. RESULTS: In the
      nipradilol preceding group, IOP was 21.4 +/- 2.3 mmHg (mean +/- SD) at baseline,
      and 16.8 +/- 1.9 mmHg at the end of latanoprost monotherapy (P < 0.01). The
      addition of nipradilol decreased IOP to 15.8 +/- 1.7 mmHg, and the change to
      carteolol, to 15.3 +/- 2.0 mmHg. In the carteolol preceding group, IOP was 21.2
      +/- 2.0 mmHg at baseline, and 17.0 +/- 2.1 mmHg at the end of latanoprost
      monotherapy (P < 0.01). The addition of carteolol decreased IOP to 15.4 +/- 1.8
      mmHg, and the change to nipradilol, to 16.3 +/- 1.9 mmHg. Additional IOP
      reduction was greater with carteolol than with nipradilol (cross-over analysis of
      variance; P = 0.0005). CONCLUSIONS: Both nipradilol and carteolol have additive
      effects when used in combination with latanoprost. Carteolol, however, may have a
      more potent effect than nipradilol.

PMID- 16453186
TI  - Prognostic factors for progression of visual field damage in patients with normal
      tension glaucoma.
AB  - PURPOSE: To evaluate the rate of progression and the prognostic factors of visual
      field damage in patients with normal-tension glaucoma (NTG). METHODS: Ninety-two
      NTG patients (92 eyes) were followed up for more than 2 years with topical
      antiglaucoma medications. All subjects were classified as having early damaged
      eyes with an initial mean deviation (MD) of -6 dB or better, moderately damaged
      eyes with MD between -6 dB and -12 dB, and severely damaged eyes with MD of -12
      dB or worse, and survival data were analyzed using regression analysis based on
      the Cox proportional hazards model. RESULTS: The probability of visual field
      stability was significantly higher in patients with moderate damage than in those
      with severe damage (P = 0.035). The patients with early damage showed no
      difference in the probability of visual field stability compared with patients
      with moderate or severe damage. The progression of visual field damage was
      significantly associated with mean intraocular pressure (IOP) (P = 0.000) or IOP
      fluctuation (P = 0.002) during follow-up regardless of the severity of the
      initial visual field damage. CONCLUSIONS: The rate of progression of visual field
      damage differed according to the severity of the initial visual field damage. IOP
      reductive medication may be effective in preventing glaucomatous visual field
      progression in patients with NTG.

PMID- 16453187
TI  - Population-based study of nonproliferative diabetic retinopathy among type 2
      diabetic patients in Kinmen, Taiwan.
AB  - PURPOSE: This study was conducted to assess the prevalence and associated factors
      of nonproliferative diabetic retinopathy among type 2 diabetic patients in
      Kinmen, Taiwan. METHODS: From 1991 to 1993, 971 type 2 diabetic patients in
      Kinmen underwent diabetic retinopathy screening performed by a panel of
      ophthalmologists using indirect ophthalmoscopy and 45 degrees color fundus
      retinal photographs. RESULTS: Of the 971 patients screened in 1991-1993, 578
      (59.5%) were examined for this study. Diabetic retinopathy was diagnosed in 127
      patients (22.0%), including nonproliferative diabetic retinopathy in 13.3%,
      proliferative diabetic retinopathy in 1.4%, legal blindness in 1.4%, and
      ungradable diabetic retinopathy in 5.9%. Significant associated factors of
      nonproliferative diabetic retinopathy based on multiple logistic regression
      analysis were fasting plasma glucose (FPG) at baseline [> or =126 mg/dl vs. <126
      mg/dl; odds ratio (OR) = 2.89; 95% confidence interval (CI), 1.01-9.09], 2-h
      postload at baseline (> or =200 vs. <200 mg/dl; OR = 1.48; 95% CI, 1.09-2.07);
      HbA1c at follow-up (> or =7% vs. <7%; OR = 6.54; 95% CI, 3.01-14.20), duration of
      diabetes (> or =15 years vs. <10 years; OR = 6.72; 95% CI, 2.13-21.18), and
      incremental systolic blood pressure between baseline and follow-up (OR = 1.02;
      95% CI, 1.00-1.04). CONCLUSIONS: In addition to the longer duration of type 2
      diabetes, FPG at baseline, poorly controlled glucose concentration, and altered
      blood pressure may increase the risk of nonproliferative diabetic retinopathy in
      type 2 diabetic patients.

PMID- 16453189
TI  - Lattice corneal dystrophy type III in patients with a homozygous L527R mutation
      in the TGFBI gene.

PMID- 16453190
TI  - A case of conjunctival leech infestation.

PMID- 16453188
TI  - Vitrectomy for myopic posterior retinoschisis or foveal detachment.
AB  - PURPOSE: To evaluate the efficacy of vitrectomy for posterior retinoschisis (RS)
      or foveal detachment (FD) associated with posterior staphyloma in myopic eyes.
      METHODS: We reviewed the records of 14 consecutive patients (53-77 years of age;
      16 eyes) with progressive visual impairment as a result of myopic RS or FD.
      Optical coherence tomography demonstrated the presence of a variety of RS and FD
      characteristics. Five eyes had RS alone, and 11 eyes had RS and FD. Two eyes with
      RS and severe FD developed retinal detachment in conjunction with a tiny macular
      hole. Vitrectomy, including posterior vitreous separation in all eyes and
      internal limiting membrane (ILM) peeling in six eyes, had been performed. The
      patients were followed postoperatively for 6 to 66 months (mean, 24 months). The
      anatomical outcome and visual acuity were retrospectively analyzed in this study.
      RESULTS: Although the two eyes with RS and severe FD developed retinal detachment
      with a macular hole after an initial vitrectomy, final retinal reattachment was
      achieved in all 16 eyes. Visual acuity improved in nine eyes and remained
      unchanged in seven eyes. CONCLUSIONS: Vitrectomy with posterior vitreous
      separation is effective for reattaching the macula and preventing a deterioration
      of vision, although eyes with RS and severe FD may be at risk for the development
      of a macular hole after the initial vitrectomy.

PMID- 16453191
TI  - Correlation between the additive effect of bunazosin and the response to
      latanoprost on intraocular pressure in patients with glaucoma treated with
      bunazosin as adjunctive therapy to latanoprost.

PMID- 16453192
TI  - Modification of an adult-sized Ahmed glaucoma valve for a small globe.

PMID- 16453193
TI  - Switching from dorzolamide to brinzolamide: effect on intraocular pressure and
      patient comfort.

PMID- 16453194
TI  - Statistical analysis of endogenous uveitis at Tokyo University Hospital (1998
      2000).

PMID- 16453195
TI  - Ocular bacterial flora in HIV-positive patients and their sensitivity to
      gentamicin.

PMID- 16453196
TI  - Case of dominantly inherited drusen accompanied by choroidal neovascularization.

PMID- 16453197
TI  - A case of unilateral occult maculopathy with normal-tension glaucoma.

PMID- 16453199
TI  - Biofilm colonization dynamics and its influence on the corrosion resistance of
      austenitic UNS S31603 stainless steel exposed to Gulf of Mexico seawater.
AB  - Viable bacterial counts, chemical markers, phospholipid fatty acid analysis
      (PLFA), and Fourier-transformed infrared spectroscopy (FTIR), together with
      electrochemical methods, were used to study biofilm dynamics and its impact on
      the corrosion resistance of UNS S31603 stainless steels exposed to the Gulf of
      Mexico seawater. Biofilms progressively accumulated, peaking on day 20, but
      finally detached. The extracellular polysaccharide (EPS)/cellular biomass ratio
      remained low most of the time, but reached its highest level (4.2+/-1.9) also on
      day 20. Viable bacterial cells reached their highest abundance earlier
      (approximately 800 CFU/cm2), on day 15. Biofilms were seen covering the stainless
      steel surfaces heterogeneously and were composed mainly of gram-negative rods,
      presumably EPS-producing bacteria. Despite the different levels of biofilm
      biomass and attachment state, field-exposed steel coupons ennobled significantly
      and showed more active pitting potentials (approximately +500 mVSCE) than on the
      abiotic control (+650 mVSCE), where no significant ennoblement occurred. These
      results suggest that the heterogeneous distribution of biofilms, as opposed to
      the quantity of surface-associated biomass, promotes formation of differential
      aeration cells, and that this in turn contributes to the ennoblement of these
      steels.

PMID- 16453198
TI  - Long-term follow-up of two sisters with Leber's Hereditary Optic Neuropathy.

PMID- 16453200
TI  - Nitrogen fixation and leaching of biological soil crust communities in mesic
      temperate soils.
AB  - Biological soil crust is composed of lichens, cyanobacteria, green algae, mosses,
      and fungi. Although crusts are a dominant source of nitrogen (N) in arid
      ecosystems, this study is among the first to demonstrate their contribution to N
      availability in xeric temperate habitats. The study site is located in Lucas
      County of Northwest Ohio. Using an acetylene reduction technique, we demonstrated
      potential N fixation for these crusts covering sandy, acidic, low N soil. Similar
      fixation rates were observed for crust whether dominated by moss, lichen, or bare
      soil. N inputs from biological crusts in northwestern Ohio are comparable to
      those in arid regions, but contribute substantially less N than by atmospheric
      deposition. Nitrate and ammonium leaching from the crust layer were quantified
      using ion exchange resin bags inserted within intact soil cores at 4 cm depth.
      Leaching of ammonium was greater and nitrate less in lichen than moss crusts or
      bare soil, and was less than that deposited from atmospheric sources. Therefore,
      biological crusts in these mesic, temperate soils may be immobilizing excess
      ammonium and nitrate that would otherwise be leached through the sandy soil.
      Moreover, automated monitoring of microclimate in the surface 7 cm of soil
      suggests that moisture and temperature fluctuations in soil are moderated under
      crust compared to bare soil without crust. We conclude that biological crusts in
      northwestern Ohio contribute potential N fixation, reduce N leaching, and
      moderate soil microclimate.

PMID- 16453203
TI  - Neurite outgrowth is directed by schwann cell alignment in the absence of other
      guidance cues.
AB  - Schwann cells enhance axonal regeneration following nerve injury in vivo and
      provide a favorable substrate for neurite outgrowth in vitro. However, much
      remains unknown about the nature of interactions that occur between Schwann cells
      and growing neurites. In this paper, we describe direct evidence of the ability
      of Schwann cell alignment alone to direct neurite outgrowth. Previously, we
      reported that laminin micro-patterns can be used to align Schwann cells and thus
      create oriented Schwann cell monolayers. In the current study, dissociated rat
      spinal neurons were seeded onto oriented Schwann cell monolayers, whose alignment
      provided the only directional cue for growing neurites, and neurite alignment
      with the underlying Schwann cells was analyzed. The orientation of neurite
      outgrowth mimicked that of the Schwann cells. Associations observed between
      neurites and Schwann cells suggest that Schwann cells may guide neurite outgrowth
      through both topographical and molecular mechanisms. This work demonstrates that
      Schwann cell alignment can direct neurite outgrowth in the absence of other
      directional cues, and provides a new method for examining neuronal-Schwann cell
      interactions in vitro.

PMID- 16453201
TI  - Biodiversity and biogeography of Fusarium species from northeastern North
      American asparagus fields based on microbiological and molecular approaches.
AB  - Sixteen Fusarium species were recovered from 52 asparagus commercial fields,
      representing all major ecological (edaphic and climatic) area of asparagus
      production in the province of Quebec, eastern Canada. This study extends our
      understanding of the geographic range of these species. It also provides
      climatological and edaphic properties linked to community changes and
      adaptations. Fusarium oxysporum and F. proliferatum were omnipresent and abundant
      in all five ecological area under study, whereas F. redolens was less frequently
      found. Species of Fusarium that produce carmine red pigmentation on potato
      dextrose agar, i.e., F. acuminatum, F. avenaceum, etc., were common at the
      northern limit of asparagus production. Abundance of red Fusarium species
      corresponded with a low isolation frequency of F. proliferatum. Nevertheless, F.
      proliferatum had a high recovery rate throughout Quebec asparagus growing areas,
      under climatic conditions as cold as those of northern Europe where this species
      is uncommon in asparagus fields. In the light of these results, redefinition of
      the geographical distribution of F. proliferatum in asparagus fields is proposed.
      Intraspecific molecular differences in F. proliferatum and F. oxysporum were
      detected in the EF-1 alpha sequences and compared with well-characterized strains
      of North America.

PMID- 16453204
TI  - Electrode array for reversing the recruitment order of peripheral nerve
      stimulation: experimental studies.
AB  - One of the most challenging problems in peripheral nerve stimulation is the
      ability to activate selectively small axons without large ones. Electrical
      stimulation of peripheral nerve activates large diameter fibers before small
      ones. Currently available techniques for selective activation of small axons
      without large ones require long-duration stimulation pulses (>500 micros) and
      large stimulation amplitude, which shorten battery life of the implanted
      stimulator and could lead to electrode corrosion. In the current study, the
      hypothesis that small axons can be recruited before large ones with narrow pulse
      width (50 micros) using an electrode array was tested in both simulations
      simulation and experiments in the cat lateral gastrocnemius (LG) model. The LG
      nerve innervates both LG and soleus muscle groups with axons within 10-13 and 8
      12 microm diameter ranges, respectively. A finite element model of LG nerve was
      constructed and simulations showed that, when activating 40% of LG, a
      conventional tripolar electrode activated only 9% of soleus whereas the electrode
      arrays of 5, 7, and 11 contacts activated 39, 46, and 60% of soleus respectively,
      suggesting that the arrays could activate small axons before fully recruiting
      large axons. In animal experiments, peak twitch force of LG and soleus were
      plotted as a function of stimulation amplitude to indicate the recruitment curve.
      At 40% activation of LG, a conventional tripolar electrode activated only 7% of
      soleus whereas the electrode arrays of 5, 7, and 11 contacts activated 43, 48,
      and 72% of soleus respectively. The electrode arrays also decreased significantly
      the recruitment curve slopes to only 10-20% of the value obtained for the
      tripolar electrode in both computer simulations and experiments. In conclusion,
      the 5-, 7-, and 11-contact arrays can be used to reverse the recruitment order of
      peripheral nerve stimulation with a narrow pulse.

PMID- 16453205
TI  - Genetics of narcolepsy and other major sleep disorders.
AB  - One third of the population is affected by a sleep disorder with a major social,
      medical, and economic impact. Although very little is known about the genetics of
      normal sleep, familial and twin studies indicate an important influence of
      genetic factors. Most sleep disorders run in families and in several of them the
      contribution of genetic factors is increasingly recognised. With recent advances
      in the genetics of narcolepsy and the role of the hypocretin/orexin system, the
      possibility that other gene defects may contribute to the pathophysiology of
      major sleep disorders is worth indepth investigation.

PMID- 16453206
TI  - Quality assessment of the visits of pharmaceutical company representatives to
      hospital pharmacists.
AB  - OBJECTIVES: To evaluate whether the quality of pharmaceutical company
      representatives' (PCRs) visits to hospital pharmacists can be improved by written
      communication of the results of an evaluation of their visits. METHODS: Pilot
      study with prospective evaluation of overall visit quality and strength of
      request for adding drugs to the hospital formulary, and of the scientific quality
      of products presentations using a standardized form. Two one-year study periods
      (59 vs. 61 visits) separated by the intervention (global results of the first
      period sent to each drug company). RESULTS: No difference was observed between
      both periods in overall visit quality (VAS 0 = null, 10 = excellent: mean 4.7
      (2.1 SD) vs. 5.2 (2.1) or strength of request for adding drug to hospital
      formulary (VAS 0 = null, 10 = extreme: 7.0 [2.6] vs. 7.2 [2.7]). Clarity and
      scientific value of products' presentations and scientific value of responses
      were better during the second study period, as a sign of quality improvement.
      CONCLUSIONS: This study suggests that systematic quality evaluation of PCRs
      visits and communication of results to drug companies may improve the scientific
      quality of products' presentation.

PMID- 16453207
TI  - The da Vinci robotic system for general surgical applications: a critical interim
      appraisal.
AB  - PRINCIPLES: The recently introduced robotic surgical systems were developed to
      overcome the limitations of conventional minimally invasive surgery. We analyse
      the impact of the da Vinci robotic system on general surgery. METHODS: The da
      Vinci operating robot is a telemanipulation system consisting of a surgical arm
      cart, a master console and a conventional monitor cart. Since its purchase in
      June 2001, 128 patients have undergone surgery using the da Vinci robot in our
      department. The mean age of the 78 female and 50 male patients was 52 (range 18
      78) years. RESULTS: The procedures included 29 cholecystectomies, 16 partial
      fundoplications, 16 extended thymectomies, 14 colonic interventions, 10
      splenectomies, 10 bariatric procedures, 7 hernioplasties, 6 oesophageal
      interventions, 5 adrenalectomies, 5 lower lobectomies, 4 neurinomectomies and 6
      others. 122 of 128 procedures (95%) were completed successfully with the da Vinci
      robot. Open conversion proved necessary in 4 patients due to surgical problems,
      and two other procedures were completed by conventional laparoscopy due to robot
      system technical errors. 30-day mortality was 0%, one redo-operation was
      necessary and two lower complications not requiring surgical re-intervention
      occurred. The resection margins of all tumour specimens were histologically
      tumour free. CONCLUSIONS: Various general surgical procedures have proved
      feasible and safe when performed with the da Vinci robot. The advantage of the
      system is best seen in tiny areas difficult of access and when dissecting
      delicate, vulnerable anatomical structures. However, in view of longer operating
      times, higher costs and the lack of adequate instruments, robotic surgery does
      not at the moment represent a general alternative to conventional minimally
      invasive surgery.

PMID- 16453208
TI  - Colonoscopic findings of symptomatic patients aged 50 to 80 years suggest that
      work-up of tumour suspicious symptoms hardly reduces cancer-induced mortality.
AB  - QUESTIONS UNDER STUDY: The risk of colorectal cancer (CRC) starts to increase at
      the age of 50 years in average persons without special risk factors. The
      significance of clinical symptoms and frequency of endoscopies done at this age
      are hitherto unknown. We do not know the stage of colorectal cancers nor the
      distribution of advanced neoplasms in symptomatic persons above 50 years. These
      data are of interest to validate the necessity of screening programmes, to define
      the target population and to interpret results of screening studies in
      asymptomatic people. METHODS: Endoscopies of the colon performed from 1991 to
      2000 in symptomatic patients aged 50 to 80 in the well-defined area of Uri were
      analysed retrospectively, focusing on symptoms leading to the endoscopy and the
      occurrence of neoplastic lesions. RESULTS: Sixteen percent of the population at
      the age of 50-80 years had a colonoscopy for workup of symptoms. A CRC was found
      in 5.5% of all patients (83 of 1514 patients), in 12.3% of patients with tumour
      suspicious symptoms, but only in 0.3% of patients with unspecific pain. Stage of
      tumours was often advanced (82% T3/T4, 38% N1-3, 21% M1). In 2.6% of patients a
      colorectal cancer was found before the age of 60, mostly in men. Advanced lesions
      were more frequent in men, increasing with age. CONCLUSIONS: A substantial part
      of the population above the age of 50 had an endoscopic workup of the colon for
      symptoms, what has to be considered when defining the target population and the
      necessary manpower of screening programmes. Tumour-suspicious symptoms were
      significant predictors for the presence of a CRC, but tumours were often already
      advanced. This underlines the importance to screen persons before developing
      symptoms.

PMID- 16453209
TI  - Aseptic meningitis, venous sinus thrombosis, intracranial hypertension and
      callosal involvement contemporaneously in a young patient with Behcet's disease.

PMID- 16453210
TI  - [Diagnostic use of ultrasound for examination of the nose and the paranasal
      sinuses].
AB  - Ultrasound is commonly performed to diagnose pathological processes of the neck
      and the salivary glands. In contrast, pathological changes of the sinuses and the
      bony structures of the face are only rarely examined sonographically. This paper
      deals with the diagnostic scope of ultrasound in the case of orbital and nasal
      fractures as well as for cases of sinus pathology excluding acute sinusitis. 51
      patients with different diseases of this area were examined using US and X-ray or
      CT scan. Fractures of the nose could all be diagnosed correctly by ultrasound,
      which is of clinical importance if children or pregnant patients are examined.
      Blow-out fractures of the orbit were not detected. In contrast, pathological
      changes of the orbit itself could be distinguished sufficiently well from those
      infiltrating the orbit and originating from the sinuses. Real-time examination
      allows the detection of infiltration of orbital muscles and the bulb of the eye
      better than any other imaging method.

PMID- 16453212
TI  - Aneurysm of the thoracic aorta--three sections of the aorta in a single scan.

PMID- 16453214
TI  - Historical ultrasound images. Exemplary renal sonography.

PMID- 16453213
TI  - [Michael J. Fox award for Daniela Berg].

PMID- 16453217
TI  - [Ultrasound of adrenal gland tumours and indications for fine needle biopsy
      (uFNB)].
AB  - The normal adrenal glands can be detected by high-resolution-sonography in a high
      percentage of cases. Sonography is also highly sensitive in the diagnosis of
      tumours of the adrenal glands. Only some of those tumours are hormonally active.
      Amongst the benign tumours, adenomas are the most frequent (up to 8%).
      Pheochromocytomas are less frequent (4.8% in uFNB statistics). Amongst the
      malignant tumours, metastases are more frequent than primary carcinomas (32.5%
      vs. 19.8% in uFNB-statistics). The adrenal glands are the fourth most common
      location of metastases. Bronchiogenic carcinomas, malignant melanomas, carcinomas
      of the breast and stomach as well as renal carcinomas metastasize into the
      adrenals most often. Much less frequent are infiltrates of lymphomas in adrenal
      glands tumours (3.4%). Incidentalomas are accidentally detected tumours of the
      adrenal glands without clinical symptoms. Malignant tumours only represent a very
      small part of incidentalomas (0.2%). They seldom show hormonal activity. In the
      case of an accidentally detected tumour, we propose a minimal laboratory profile
      (24-h-urinary-catecholamines, dexamethasone-test, electrolyte metabolism). The
      uFNB of the adrenal glands has a high sensitivity (90-95%). Complications are
      rare (pneumothorax, bleeding, pain; approximately 3%). Biopsy of
      pheochromocytomas (2-4% malignant) is dangerous because of the risk of provoking
      a hypertensive crisis. Case studies have been published about this problem. On
      the other hand, numerous cases of uncomplicated biopsies have also been
      published. Considering the excellent imaging methods and laparoscopic surgery
      methods on hand, the indication of FNP is restricted to the following cases: 1.
      the presence of a metastasis leading to therapeutical consequences; 2. suspected
      lymphoma 3. undefined lesion (3-5 cm), hormonally inactive, without typical signs
      of a tumour 4. patients refusing surgery. 5. uFNB in case of tumours of undefined
      dignity is only justified in specific cases. Recommendations for this procedure
      in accidentally detected tumours of the adrenal glands: < 3 cm and hormonally
      inactive --> US-follow up, > 5 cm + suspected tumour --> surgery, 3-5 cm uFNB
      after laboratory diagnostics.

PMID- 16453218
TI  - Contrast enhanced sonography of focal splenic lesions with a second-generation
      contrast agent.
AB  - OBJECTIVE: Contrast enhanced sonography (CES) of second generation contrast media
      have shown a spleen-specific uptake of the microbubble contrast agent. The aim of
      this study was to investigate the ability of a second generation contrast agent
      to enhance splenic lesions. METHODS: From October 2003 to September 2004, 46
      consecutive patients with focal (peri-) splenic lesions on B-mode sonography were
      studied by CES using a transpulmonary second-generation contrast agent (SonoVue).
      Data were retrospectively evaluated. Diagnosis of the patients were infarction (n
      = 9), lymphoma (n = 7), metastasis (n = 6), injury (n = 4), haemangioma/splenoma
      (n = 6), accessory spleen (n = 3), cyst (n = 2), and unknown cause (n = 9).
      Diagnosed of splenic lesions was confirmed by histology (n = 5), contrast
      enhanced computed tomography (n = 25), MRI (n = 4), scintigraphy (n = 1), and
      follow up (n = 38). Extent of enhancement (EE) was evaluated during the arterial
      phase (5-30 s) and the parenchymal phase (3-5 minutes): EE of focal splenic
      lesions was determined using the surrounding splenic tissue as an in vivo
      reference, and classified as anechoic vs. hypoechoic vs. isoechoic vs.
      hyperechoic vs. mixed. The contribution of CES to the final diagnosis was
      classified as low, helpful or highly necessary. RESULTS: In all but one patient
      enhancement of normal splenic tissue occurred. During the arterial and
      parenchymal phase, lesions were found to have anechoic 10/10, hypoechoic 12/24,
      isoechoic 12/7, hyperechoic 7/0 and mixed enhancement 5/5, respectively. Value of
      CES for final diagnosis was low n = 24 (52%) (7 lymphomas, 6 metastases, 2 cysts,
      9 unknown), helpful n = 9 (20%) (4 infarctions, 2 ruptures, 3 accessory spleens)
      and highly necessary n = 13 (28%) (5 infarctions, 2 ruptures, 6
      haemangiomas/splenomas). CONCLUSION: Contrast-enhanced sonography is of
      diagnostic value in subgroups of patients with (peri-)splenic lesions (48%):
      including splenic infarction, splenic rupture, splenic haemangioma/splenoma, and
      accessory spleen.

PMID- 16453219
TI  - Evaluation of cerebral perfusion deficit in stroke patients using new
      transcranial contrast imaging CPS technology--preliminary results.
AB  - BACKGROUND AND PURPOSE: Contrast-enhanced transcranial duplex sonography can be
      used to examine cerebral perfusion. This technique, however, is still faced with
      methodological problems. The aim of the present study is to evaluate cerebral
      perfusion deficit after administration of the contrast agent SonoVue in acute
      stroke patients using new contrast imaging software. METHODS: Ten subjects (6
      male stroke patients and 4 healthy volunteers), were examined using transcranial
      duplex sonography (Acuson Sequoia 512 Ultrasound System) after a bolus injection
      of the contrast agent SonoVue. The transcranial examination was performed using
      transient response harmonic grey scale imaging with refill kinetics. The Sequoia
      ultrasonographic system was equipped with a new contrast harmonic imaging
      software "Cadence contrast pulse sequencing technology" (CPS). Triggered images
      with the mechanical index (MI) at 1.1 as well as continuous registration with MI
      at 0.28 were used for the evaluation of time intensity curves in several regions
      of interest. The sonographically imaged hypoperfused areas were compared with
      findings from MR imaging. RESULTS: In all healthy volunteers, the contrast
      enhanced signal could be recognized well in the ipsi- and also in the
      contralateral hemisphere up to the skull crown. In stroke patients, the perfusion
      deficit in the area of the MCA could be detected ipsilaterally in all subjects
      using triggered registration. Additionally, the area of MCA infarction could also
      be visualized in two patients using contralateral insonation. The low MI
      continuous imaging was successful in three patients. For all patients, the
      ischaemic region corresponded well in shape and size with the findings from MR
      imaging. CONCLUSIONS: CPS enhances the possibility of perfusion-imaging in
      cerebral microcirculation and of perfusion-deficit-imaging in patients with
      cerebral ischaemia. Further studies with a larger number of patients should be
      carried out to improve this method.

PMID- 16453220
TI  - Utility of colour Doppler endoscopic ultrasound evaluation and guided therapy of
      submucosal tumours of the upper gastrointestinal tract.
AB  - BACKGROUND AND AIMS: Endoscopic ultrasound is considered the method of choice for
      evaluation of submucosal tumours. Endoscopic therapy of selected lesions
      represents a useful mini-invasive approach. The aim of this study was to assess
      the endoscopic management of submucosal tumours of the upper gastrointestinal
      tract (GIST), with emphasis on the use of colour and power Doppler endoscopic
      ultrasound. METHODS: The study included 35 consecutive patients referred to
      endoscopic ultrasound with submucosal tumours of the upper gastrointestinal
      tract. Colour and power Doppler imaging were performed with radial or linear
      instruments in all patients and allowed a better characterisation of the
      submucosal lesions. Histology was obtained in 22 patients and permitted a correct
      diagnosis, as well as confirmation or exclusion of malignancy. RESULTS: In 18
      patients (51.4%) there was discrepancy between the suspected endoscopic diagnosis
      and the diagnosis made by endoscopic ultrasound. Most of the malignant GISTs had
      significant intratumoural vessels detected by colour or power Doppler EUS (5 out
      of 6 patients, 83.3%), as compared with the benign GISTs (2 out of 7 patients,
      28.6%). Colour Doppler EUS was essential, both to diagnose and to direct therapy
      in vascular submucosal lesions (two haemangiomas). The same technique was useful
      to better characterise lipomas or cysts. CONCLUSIONS: Endoscopic ultrasound
      management of submucosal tumours was enhanced by the use of colour and power
      Doppler imaging. A precise management plan, supported by colour and power Doppler
      findings improved the diagnostic options and increased the feasibility and safety
      of endoscopic ultrasound guided therapeutic interventions.

PMID- 16453221
TI  - Sonographic imaging of the sciatic nerve division in the popliteal fossa.
AB  - BACKGROUND: We studied the anatomy of the sciatic nerve and its division into the
      tibial and peroneal part using handheld ultrasound in adults. We wanted to
      evaluate the feasibility of ultrasound-guided identification of the sciatic nerve
      in the popliteal fossa and the correlation of the findings by ultrasound with
      patients' characteristics. METHODS: 74 volunteers were randomly selected. Using a
      handheld ultrasound system with a 5-10 MHz linear array probe the popliteal fossa
      and the back of the thigh were examined and measured. Using a caliper the
      distance of the joint line to the nerve division was measured. The sciatic nerve
      and its division were depicted by ultrasound. RESULTS: We could depict the
      sciatic nerve in all volunteers and its division in 53 of 74 (72%) volunteers.
      The position of nerve division showed large anatomic variation. A significant
      correlation between the width of the knee-joint line and the depth of the nerve
      division could be demonstrated. We conclude that handheld ultrasound is able to
      depict the sciatic nerves division. To block the nerve by one injection a more
      proximal access or visualization by mobile ultrasound is recommended. In addition
      the surrounding anatomic structures can be depicted as well.

PMID- 16453222
TI  - [Trans-fontanellar Doppler sonography of the intracranial veins in infants--part
      I--Normal values].
AB  - Doppler sonographic flow measurements in the intracranial veins of infants are
      not often applied. For the understanding of intracranial pathology such as
      vascular malformations, intracranial hemorrhagic infarction and venous
      thrombosis, a thorough understanding of the anatomical position and of the normal
      flow profiles and flow velocities in intracranial veins is essential. We describe
      the normal anatomic course of the cerebral veins and their flow profiles and flow
      velocities in infants. In sagittal sections, the following veins can be shown by
      colour coded Doppler sonography and measured by pulsed Doppler sonography: The
      superior and inferior sagittal sinus, and the straight sinus as well as the
      internal cerebral vein, the vein of Galen and the thalamostriatic veins. In
      coronal sections, the medullary and subependymal veins, the terminal veins, the
      internal cerebral veins, the great vein of Galen, the superior sagittal, straight
      and transverse sinus can be demonstrated and measured.

PMID- 16453223
TI  - [Sonographic detection of kidney infarctions using ultrasound contrast media].
AB  - Contrast-enhanced CT is currently the gold standard for the diagnosis of kidney
      infarction. Particularly in patients with renal insufficiency, however, the use
      of iodine contrast media is limited. Sonographic examination using ultrasound
      contrast media may be an alternative for these patients. CASE REPORTS: We
      examined three patients with suspected ischaemic kidney infarction with
      ultrasound contrast media. Scanning was performed with low mechanical index, and
      SonoVue was used as by contrast-enhancing agent. In all three patients, kidney
      infarctions were clearly shown. In two patients, the lesions were confirmed by
      contrast-enhanced CT, in one no CT was performed because of impaired renal
      function. CONCLUSION: Kidney infarctions can reliably be detected by contrast
      enhanced ultrasound using SonoVue as contrast agent. This is particularly
      valuable in patients with renal impaired renal function and other
      contraindications against iodine contrast media.

PMID- 16453224
TI  - Giant hydronephrosis mimicking echinococcal cyst.
AB  - Cases of giant hydronephrosis are rare and usually contain no more than one to
      two liters of fluid in the collecting system. We report a remarkable case of
      giant hydronephrosis of > 17.5 Kg mimicking a huge echinococcal cyst.

PMID- 16453225
TI  - Ultrasound perfusion imaging of cysts in the midbrain.
AB  - AIM: Cerebral ultrasound perfusion examinations have been focused on the
      diencephalic plane. We describe perfusion abnormalities in the mesencephalon.
      METHOD: Phase-Inversion-Harmonic-Imaging (PIHI, Siemens Sonoline Elegra) was
      performed in a patient with ponto-mesencephalic cysts, that was defined by MRI.
      The signal increase (bolus kinetics, SonoVue) was quantified for peak-signal
      increase (PSI) and time-to-peak (TTP). RESULTS: PSI and TTP could be quantified
      for the ipsi- and contralateral posterior cerebral arteries, the ipsilateral
      middle cerebral artery, the mesencephalon and the ipsilateral temporal lobe. The
      contrast agent influx was diminished or extinct in the area of the cysts. PSI and
      TTP delineated the area of the cystic structure well. CONCLUSION: PIHI in the
      mesencephalic plane is feasible and allows identification of pathological
      structures within the mesencephalon.

PMID- 16453230
TI  - [Ultrasonic diagnosis equipment--sound interpretation].

PMID- 16453231
TI  - [Basis for the range of use for interventional sonography].

PMID- 16453240
TI  - [OPD and DKPM].

PMID- 16453241
TI  - [The Quality of Life Questionnaire EQ-5D: modelling and norm values for the
      general population].
AB  - The EQ-5D is a short questionnaire for measuring health related quality of life.
      The aim of the present study is to test psychometric properties of this
      instrument when applied to the general population. 2022 subjects between 16 and
      93 years of age were randomly selected and tested with the EQ-5D. 60 % of the
      sample reported no health problems in all items, that is, there was a great
      ceiling effect. The comparison between two models with preference based index
      measurement and one simple sum score showed that the sum score is at least as
      appropriate as the two other more sophisticated models. The visual analogue scale
      of the EQ-5D proved to be practicable and useful for the application in the
      general population. Norm values for the visual analogue scale and the EQ-5D are
      presented.

PMID- 16453242
TI  - [The "Medication Experience Scale for Immunosuppressants" (MESI): initial results
      for a new screening instrument in transplant medicine].
AB  - BACKGROUND: After an organ transplant, immunosuppressants must be taken on a
      regular basis to prevent rejection of the transplanted organ. To our knowledge,
      there have been no studies to date on how transplant recipients experience the
      effects and side effects of immunosuppressants. The present study tested a newly
      developed screening instrument that records the subjective experiences and
      cognitive attitudes of patients vis-a-vis their immunosuppressive medication.
      METHOD: 98 patients were questioned before a heart, lung, liver or kidney
      transplant and 12 months after the transplant by means of various psychosocial
      measuring instruments (Sense of Coherence, SOC; Hospital Anxiety and Depression
      Scale, HADS-D; Quality of Life, SF-36; Satisfaction with Life, FLZ; Social
      Support, F-SOZU). 12 months after the transplants were performed, seven further
      items intended to measure the subjective experiences and cognitive attitudes of
      the patients vis-a-vis their immunosuppressive medication were used. The treating
      doctors assessed patients' overall compliance 12 months after the transplant
      operation. RESULTS: Die "Medication Experience Scale for Immunosuppressants"
      (MESI) showed an internal consistency (Cronbach's alpha) of 0.78. Its values
      correlated significantly negatively with the sense of coherence recorded before
      the transplant. There were also significantly negative correlations with physical
      functioning, mental health, satisfaction with life and social support, as well as
      significantly positive ones with anxiety and depression 12 months post
      transplant. In a comparison of organ groups, lung-transplant patients exhibited
      the highest MESI values. Patients whose compliance was assessed as "very good"
      experienced the effects of the immunosuppressants less intensely than patients
      with "good" to "moderate" compliance. Sensitivity of the MESI scale with regard
      to compliance was 0.81, with a specificity of 0.71, a positive predictive value
      of 0.68, and a negative predictive value of 0.83. The cut-off value between "very
      good" and "limited" compliance was a scale score of 15 points. CONCLUSION: The
      MESI is a short, easy-to-use screening instrument for recording the subjective
      experiences and attitudes of patients after an organ transplant. Of clinical
      significance is the correlation with compliance. Patients with a scale score of >
      15 in particular should be spoken to by their treating doctor with regard to
      their attitudes to and experiences of the immunosuppressants, as well as with
      regard to their compliance behaviour.

PMID- 16453244
TI  - [The WHOQOL-OLD].
AB  - The WHOQOL-OLD is an international cooperation of 22 research centres under the
      sponsorship of the WHO for the development of an intercultural instrument for the
      assessment of quality of life in old age. This article presents the results of
      the empirical investigations (field trial) for the German version of WHOQOL-OLD.
      Based on the results of the focus groups which were conducted in the first step
      of the project new items were generated and the dimensional structure was
      determined. Items were then tested and their number reduced using both classical
      and modern psychometric methods. A field trial was then carried out testing
      psychometric characteristics and standardization of the questionnaire. The
      outcome of this study is a 24-item 6-facet add-on module which can be used with
      the WHOQOL-BREF or the WHOQOL-100 for assessment of quality of life in older
      adults.

PMID- 16453243
TI  - [The exploration of the depressive personality disorder].
AB  - Lately the concept of the depressive personality disorder has been regarded more
      often again in the context of chronic and subthreshold forms of depression. The
      purpose of the present study was the psychometric evaluation of a German version
      of the "Depressive Personality Disorder Inventory" (DPDI), which is a
      questionnaire for the exploration of the depressive personality disorder. A total
      of 138 depressive patients and controls were included in the study. The inter
      rater-reliability as well as the internal consistency and the test-retest
      reliability of the DPDI revealed satisfactory and good results. A short version
      of the DPDI was developed by means of a factor analysis. Medium correlations were
      found between the DPDI and two interviews for the depressive personality
      disorder. These results are discussed and it is concluded that the DPDI as well
      as its short version are reliable, valid and economic self-rating instruments for
      the exploration of the depressive personality disorder.

PMID- 16453245
TI  - [Psychometric evaluation of the German version of the temperament questionnaire
      TEMPS-A].
AB  - One aim of the present study was the psychometric evaluation of the German
      version of the questionnaire TEMPS-A of Akiskal, Mundt, Maier and Angst , which
      explores five affective temperaments. Another aim was to create a short version
      of the questionnaire. For that purpose the TEMPS-A was filled in by n = 62 in
      patients who suffered from Major Depression. Then the relation between the five
      types of temperament and the big five personality factors was examined. The
      intercorrelations of the five temperament scales of the TEMPS-A showed mainly
      moderate associations. The correlations with the big five personality factors
      resulted in significant associations of all temperaments with neuroticism. By
      factor analyses, conducted for each scale of the TEMPS-A, we developed a short
      form of the TEMPS-A with 30 items. The evaluation of the TEMPS-A is just
      beginning. The TEMPS-A is an important basis for the further examination of the
      relationship between temperament and psychiatric disorders.

PMID- 16453247
TI  - Parkinsonism and/or cognitive impairment with valproic acid therapy: a report of
      ten cases.
AB  - BACKGROUND: Valproic acid (VPA) is commonly prescribed and is generally
      considered to have a good safety profile. Severe neurological side effects, such
      as acute encephalopathy or tremor, are well-known. Parkinsonian syndromes and
      cognitive impairment have been very rarely reported with this drug. METHODS: Ten
      cases of reversible parkinsonism associated with VPA in 6 women and 4 men,
      associated with marked cognitive impairment in six cases, are described. These
      side effects sometimes occurred after several years of good tolerability.
      RESULTS: All patients had serum levels within the therapeutic range (50-100
      microg/ml). Symptoms improved several weeks or months after discontinuation of
      VPA therapy in every case. CONCLUSIONS: Several cases of parkinsonian syndromes
      have been reported in the literature, but usually in children or young adults.
      These symptoms had an insidious and progressive onset. Clinical features can
      mimic Parkinson's disease and may be confusing, especially when they occur in
      older patients. The mechanism of these disorders is currently unknown, but
      several hypotheses have been proposed. Despite the good safety of VPA therapy for
      several years, a drug-induced mechanism of parkinsonism or cognitive impairment
      must be considered in all patients treated with VPA, as discontinuation of the
      drug can induce significant improvement of the patient's neurological and mental
      status.

PMID- 16453246
TI  - Combined treatment with citalopram and buspirone: effects on serotonin 5-HT2A and
      5-HT2C receptors in the rat brain.
AB  - INTRODUCTION: We wanted to elucidate whether the proposed advantages of
      citalopram-buspirone combination treatment are related to changes in 5-HT(2A/C)
      receptor-mediated neurotransmission. METHODS: The affinity of buspirone to 5-HT2A
      and 5-HT2C receptors was measured in vitro, and the influence of buspirone on 5
      HT2C receptor-mediated phosphoinositide hydrolysis was estimated. Four groups of
      rats received citalopram (10 mg/kg), buspirone (6 mg/kg), citalopram-buspirone
      combination, or saline once a day s.c. for 14 days. Treatment effects on 5-HT2A
      and 5-HT2C receptors were investigated by receptor autoradiography with
      antagonist and agonist radioligands. RESULTS: Buspirone was found to be a weak 5
      HT2C receptor antagonist, with a low affinity for 5-HT2A and 5-HT2C receptors.
      Repeated buspirone-citalopram combination treatment markedly decreased
      [3H]ketanserin and [125I]DOI binding to 5-HT2A receptors. Repeated administration
      of buspirone and buspirone-citalopram combination increased the affinity of
      [3H]mesulergine toward 5-HT2C receptors, and buspirone-citalopram combination
      also decreased [125I]DOI binding to 5-HT2C receptors. DISCUSSION: We suggest that
      downregulation of brain 5-HT2A receptors and possibly of 5-HT2C receptor agonist
      sites is involved in the beneficial clinical effects of buspirone-SSRI
      augmentation treatment. Furthermore, a conversion of brain 5-HT2C receptors from
      high- to low-affinity state may provide an additional mechanism for the anti
      anxiety effects of buspirone.

PMID- 16453248
TI  - Effect of sub-chronic treatment with Jarsin (extract of St John's wort, Hypericum
      perforatum) at two dose levels on evening salivary melatonin and cortisol
      concentrations in healthy male volunteers.
AB  - OBJECTIVE: The aim of the present study was to measure the effect of two doses of
      extracts from Hypericum perforatum (HP), Jarsin, on evening salivary cortisol and
      NA-mediated melatonin in healthy male volunteers. METHODS: Twenty healthy male
      volunteers were randomly given a low or high dose of Jarsin for 7 days. Saliva
      samples for cortisol and melatonin, and overnight urine samples were collected
      for cortisol and 6-sulfatoxymelatonin and measured by specific radioimmunoassays.
      RESULTS: Treatment significantly increased salivary cortisol throughout the whole
      collection period in the low dose group but had no discernable effect in the high
      dose group. Salivary melatonin was not increased in either dose group following
      treatment. CONCLUSION: Salivary cortisol was enhanced in the low dose group only
      and melatonin was not affected by either treatment. We suggest that HP may
      enhance salivary cortisol via a U-shaped dose-response relationship and that this
      may be mediated through a 5-HT2 mechanism.

PMID- 16453249
TI  - Transdermal rivastigmine treatment does not worsen impaired performance of
      complex motions in patients with Alzheimer's disease.
AB  - BACKGROUND: There is a debate about the deterioration of fine motor behavior
      during treatment with cholinesterase inhibitors. METHODS: We used an instrumental
      motor test, which demands a complex motion series. Thereby we assessed motor
      function in patients with Alzheimer's disease (AD), in patients with mild
      cognitive impairment (MCI), and in controls. We also performed this task and a
      complex reaction time paradigm (CRT) during a six-week open-label safety study
      using transdermal delivery of the cholinesterase inhibitor rivastigmine.
      OBJECTIVES: To investigate (1) the performance of complex movements during
      deterioration of cognitive function and (2) the impact of rivastigmine on fine
      motor behavior and CRT outcomes in AD patients. RESULTS: There were significant
      differences in the motor test outcomes, particularly when performed with the left
      non-dominant hand, between controls and patients with AD and MCI. Rivastigmine
      did not deteriorate assessed fine motor skills and CRT results. CONCLUSION: Our
      study shows an impaired carrying out of complex motion series during
      neurodegeneration associated with cognitive dysfunction. Rivastigmine selectively
      inhibits the predominant cortical and hippocampal G1 cholinesterase isoform;
      therefore, hypothetically no deterioration of fine motor behavior appeared during
      transdermal rivastigmine treatment. We assume that a putative drug-induced
      increase in speed and attention did not offset a deterioration of motion
      performance because we found no significant changes in the CRT results.

PMID- 16453250
TI  - In vitro toxicity of clozapine, olanzapine, and quetiapine on granulocyte
      macrophage progenitors (GM-CFU).
AB  - INTRODUCTION: Atypical antipsychotics may lead to agranulocytosis because of the
      apoptosis caused by cells binding nitrenium molecules. Studies showing the direct
      myelotoxicity of clozapine were undertaken years ago using different assays, and
      thus it is difficult to compare them with those of clozapine's analogues that
      have been more recently reported as causing neutropenia, agranulocytosis, and
      thrombocytopenia. METHODS: We compared the direct toxicity of clozapine,
      olanzapine, quetiapine, and chlorpromazine using a previously standardized GM-CFU
      assay validated for predicting neutropenia. RESULTS: The results showed that all
      of the drugs were characterized by dose-dependent toxicity, which was greatest in
      the case of chlorpromazine (IC90 = 10.02 +/- 0.69 microg/mL), followed by
      olanzapine (IC90 = 13.43 +/- 1.23 microg/mL), clozapine (IC90 = 44.71 +/- 4.42
      microg/mL), and quetiapine (IC90 = 137.24 +/- 15.36 microg/mL). DISCUSSION: These
      data agree with recent clinical reports concerning the direct or mediated toxic
      effects of olanzapine on progenitor and committed cells (GM-CFU) and suggest that
      the correlation between its plasma levels and clinical effects warrants further
      investigation. There are no published data concerning the bone marrow
      pharmacokinetics of atypical antipsychotics or their possible bioactivation by
      the bone marrow cell compartment, but our findings suggest that they may affect
      hematopoiesis in different ways, such as the direct action of them or their
      metabolites due to bioactivation by hematopoietic cells themselves.

PMID- 16453252
TI  - Efficacy and safety of outpatient alcohol detoxification with a combination of
      tiapride/carbamazepine: additional evidence.
AB  - BACKGROUND: Few medications have been tested for outpatient alcohol
      detoxification. Previously we had shown a combination of carbamazepine and
      tiapride to be effective in an open study. This database is an extension of our
      previous work. METHODS: This was an open prospective study to examine the
      efficacy, practicability and medical safety of a combination of tiapride and
      carbamazepine in outpatient detoxification of alcohol dependent patients.
      Patients were carefully screened for relevant neuropsychiatric disorders and then
      seen on a daily outpatient basis. RESULTS: A total number of 116 consecutively
      admitted patients entered the programme; 107 (92%) successfully ended the
      treatment. The mean initial dose for tiapride was 289 mg and for carbamazepine
      502 mg. No serious medical complications or adverse events were observed except
      for one case of delirium tremens. Only four patients dropped out because of side
      effects. In general medication was well tolerated. Withdrawal symptomatology as
      indicated by CIWA-A-scores decreased over time. CONCLUSIONS: Results from this
      study give further evidence for a combination of tiapride and the anticonvulsant
      carbamazepine as an effective and safe treatment for outpatient alcohol
      detoxification in patients with moderate severity of withdrawal syndrome. Further
      randomized trials are warranted to examine the efficacy of this combination in
      outpatient alcohol withdrawal.

PMID- 16453251
TI  - Renin-angiotensin-aldosterone system, HPA-axis and sleep-EEG changes in
      unmedicated patients with depression after total sleep deprivation.
AB  - BACKGROUND: Changes in the activity of the renin-angiontensin-aldosterone system
      (RAAS) in depression have recently been reported. Renin and aldosterone secretion
      are coupled to sleep in healthy subjects. As total sleep deprivation (TSD) leads
      to a rapid mood improvement in patients with depression, it is of interest to
      investigate its effect on the response of the RAAS in the recovery night in this
      population as a possible probe for the neurobiological effects of TSD and
      potentially other rapid acting antidepressive interventions. Additionally we
      explored the HPA-system and the sleep-EEG-changes. METHODS: We compared the sleep
      related activity of the RAAS before and after TSD in seven depressed patients.
      After an accommodation night, a polysomnographic examination was performed
      between 23.00 h and 7.00 h. This was followed by 40 h of TSD and a second
      polysomnography. During the examination blood samples were taken in the night
      every 20 min for analysis of renin, aldosterone, ACTH and cortisol. RESULTS:
      During recovery-sleep renin was significantly increased (p < 0.05). Aldosterone
      showed no change. ACTH and cortisol were decreased by trend in the first half of
      the night. REM-density and intermittent wakefulness was significantly decreased
      (p < 0.05), whereas slow wave sleep increased by trend in the first half of the
      night. CONCLUSION: TSD in patients with depression leads to an increase in renin
      secretion and a concomitant trend for a decrease in HPA axis activity in the
      recovery night. These changes could be a "fingerprint" of a rapidly
      antidepressive treatment.

PMID- 16453253
TI  - Common alterations in the serotonin transporter in platelets and lymphocytes of
      psychotic patients.
AB  - INTRODUCTION: Given the controversial data concerning the role of the serotonin
      (5-HT) transporter in psychosis, our study was aimed to investigate this
      structure by means of the measurements of the re-uptake kinetics and of the
      protein density, in both platelets and lymphocytes of 25 out- and inpatients with
      different psychotic disorders. METHODS: Diagnoses, according to DSM-IV criteria,
      were bipolar 1 disorders with mood incongruent psychotic features (14), mixed
      states (7) and schizophrenia (4). Twenty-five matched healthy subjects were also
      selected as the control group. Platelet and lymphocyte membranes were prepared
      according to standardized protocols, as were the [3H]5HT re-uptake and
      [3H]paroxetine ([3H]Par) binding. RESULTS: The results of this study showed a
      decreased density of the [3H]Par binding sites coupled with a reduced velocity of
      [3H]5-HT re-uptake in both platelets and lymphocytes of psychotic patients, as
      compared with healthy control subjects. CONCLUSION: These findings would suggest
      a general abnormality of the 5-HT system in psychotic patients, probably not
      confined only to the brain.

PMID- 16453254
TI  - Massive creatine kinase elevations with quetiapine: report of two cases.
AB  - Massive elevations of serum creatine kinase (CK) can occur in a significant
      number of patients treated with neuroleptics in the absence of neuroleptic
      malignant syndrome (NMS). We report two cases of CK-elevations associated with
      quetiapine treatment, which disappeared after drug discontinuation. To our
      knowledge, case number one is the first case of quetiapine-induced CK elevation
      in a neuroleptic-naive patient. We thus suggest CK assessment when myalgia occurs
      with neuroleptic treatment.

PMID- 16453255
TI  - Predictors of immunity after a major serogroup W-135 meningococcal disease
      epidemic, Burkina Faso, 2002.
AB  - BACKGROUND: The African meningitis belt undergoes recurrent epidemics caused by
      Neisseria meningitidis serogroup A. During 2002, Burkina Faso documented the
      first large serogroup W-135 (NmW-135) meningococcal disease epidemic. To
      understand the emergence of NmW-135, we investigated meningococcal carriage and
      immunity. METHODS: Immediately after Burkina Faso's epidemic, we conducted a
      cross-sectional survey of meningococcal carriage and seroprevalence in an
      epidemic and a nonepidemic district. We identified predictors of elevated NmW-135
      serum bactericidal activity (SBA), a functional correlate of protection, using
      multivariate logistic regression. RESULTS: The NmW-135 carriage rate was 25.2% in
      the epidemic district and 3.4% in the nonepidemic district (P<.0001). Compared
      with residents of the nonepidemic district, those of the epidemic district had
      higher geometric mean titers of NmW-135 SBA (P<.0001). NmW-135 SBA titers>or=1:8,
      an estimated protective threshold, were observed in 60.4% and 34.0% of residents
      of the epidemic and nonepidemic district, respectively (P=.0002). In a
      multivariate model, current NmW-135 carriage, age, and residence in the epidemic
      district were independent predictors of having an NmW-135 SBA titer>or=1:8.
      CONCLUSIONS: Extensive NmW-135 carriage and transmission in the epidemic area
      caused residents to acquire natural immunity. Serial carriage and seroprevalence
      surveys could establish the duration of immunity in the population. The
      persistent circulation of NmW-135 underscores the potential for periodic NmW-135
      epidemics in Africa.

PMID- 16453256
TI  - Risk factors for cervicitis among women with bacterial vaginosis.
AB  - BACKGROUND: Cervicitis commonly occurs in women with bacterial vaginosis (BV),
      often without concomitant chlamydial or gonococcal infection. The risk factors
      for cervicitis have not been described. METHODS: We characterized the risk
      factors for cervicitis, which is defined as endocervical mucopurulent discharge
      or easily induced bleeding, among women with BV who were 14-45 years of age.
      Associations between cervicitis and the characteristics of the subjects,
      including the presence of specific vaginal bacteria and chlamydial or gonococcal
      infection detected by strand displacement assay, were analyzed. RESULTS: Of 424
      women with BV, 63 (15%) had cervicitis. Of these 63 women, only 8 (13%) had
      chlamydia or gonorrhea. The risk factors for cervicitis, adjusted for variables,
      included older age (P<.001, for trend), <or=12 years of education (odds ratio
      [OR], 2.4 [95% confidence interval {CI}, 1.3-4.6]; P=.006), new male sex partner
      (OR, 2.7 [95% CI, 1.4-5.4]; P=.004), female sex partner (OR, 6.2 [95% CI, 1.3
      28.3]; P=.02), recent oral sex (OR, 2.3 [95% CI, 1.2-4.2]; P=.008), and absence
      of vaginal H2O2-producing Lactobacillus species (OR, 2.7; 95% CI, 3.3-5.9;
      P=.01). No association with cervicitis was seen for current douching or smoking,
      race, time since or frequency of intercourse, or presence or quantity of vaginal
      bacteria other than H2O2-producing Lactobacillus species. CONCLUSIONS: Cervicitis
      is common among women with BV and is associated with some risk factors that are
      distinct from those associated with endocervical infection with Neisseria
      gonorrhoeae or Chlamydia trachomatis. Absence of H2O2-producing lactobacilli may
      contribute to the development of cervicitis.

PMID- 16453257
TI  - Efficient neutralization of anthrax toxin by chimpanzee monoclonal antibodies
      against protective antigen.
AB  - Four single-chain variable fragments (scFvs) against protective antigen (PA) and
      2 scFvs against lethal factor (LF) of anthrax were isolated from a phage display
      library generated from immunized chimpanzees. Only 2 scFvs recognizing PA (W1 and
      W2) neutralized the cytotoxicity of lethal toxin in a macrophage lysis assay.
      Full-length immunoglobulin G (IgG) of W1 and W2 efficiently protected rats from
      anthrax toxin challenge. The epitope recognized by W1 and W2 was conformational
      and was formed by C-terminal amino acids 614-735 of PA. W1 and W2 each bound to
      PA with an equilibrium dissociation constant of 4x10-11 mol/L to 5x10(-11) mol/L,
      which is an affinity that is 20-100-fold higher than that for the interaction of
      the receptor and PA. W1 and W2 inhibited the binding of PA to the receptor,
      suggesting that this was the mechanism of protection. These data suggest that W1
      and W2 chimpanzee monoclonal antibodies may serve as PA entry inhibitors for use
      in the emergency prophylaxis against and treatment of anthrax.

PMID- 16453258
TI  - Effective dosing of lipid A analogue E5564 in rats depends on the timing of
      treatment and the route of Escherichia coli infection.
AB  - BACKGROUND: E5564, a competitive lipid A antagonist, inhibits endotoxin
      stimulated inflammation and is under study in patients with sepsis. METHODS: We
      tested whether clinically relevant variables, including the timing of treatment
      and the route of infection, influenced the effective dosing of E5564 in
      Escherichia coli-challenged rats. RESULTS: All E5564 doses (0.3, 1.0, 2.0, and
      3.0 mg/kg intravascular bolus followed by 10% of the bolus dose infused hourly
      for 24 h) administered 1 h before intravascular E. coli challenge similarly
      reduced the risk of death. Delaying the start of E5564 to 1 or 3 h after
      intravascular E. coli challenge significantly reduced the beneficial effect of
      the doses tested. However, increasing the dose of E5564 reversed some loss of
      efficacy for delayed treatment (P=.004, for increasing benefit with increasing
      dose at 1 h). During intrabronchial or intraperitoneal (extravascular) E. coli
      challenge, the pattern of effective E5564 dosing was the inverse of that for
      intravascular E. coli challenge (P=.001, for the interaction)--lower doses of
      E5564 were beneficial and higher doses were not (0.03, 0.3, 1.0, 2.0, and 3.0
      mg/kg bolus followed by infusion) (P=.05, for decreasing benefit with increasing
      dose at 1 h). CONCLUSION: These findings suggest that, for maximal clinical
      benefit, E5564 should be given early and that dosing should be adjusted upward
      for intravascular infection and downward for extravascular infection.

PMID- 16453259
TI  - Genetic determinants of capsular serotype K1 of Klebsiella pneumoniae causing
      primary pyogenic liver abscess.
AB  - BACKGROUND: Primary pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae
      is an emerging infectious disease. Capsular serotype K1 and the magA gene have
      been reported to be associated with this disease. METHODS: The prevalence of magA
      was determined by polymerase chain reaction (PCR). The sequences of the magA
      flanking region were completed by inverse PCR and direct sequencing. Serotyping
      was performed by double immunodiffusion. Insertion mutations and trans
      complementation were used to define the K1 genetic determination region. RESULTS:
      Thirty-five of 42 strains from patients with PLA were magA positive, whereas only
      1 of 32 non-PLA strains was magA positive. All 36 magA-positive strains were
      serotype K1, and the 38 magA-negative strains were not (36/36 vs. 0/38; P<.0001).
      Sequencing of the magA flanking region revealed a putative capsular
      polysaccharide synthesis (cps) region; this region was 25 kb in length and
      contained 20 open reading frames (ORFs); of these ORFs, 9 were cotranscribed as
      part of an operon and differed from both MGH78578 and the Chedid strain. Mutation
      of 4 genes in this region turned the mutant strains anti-K1 negative. Trans
      complementation restored the K1 phenotype. CONCLUSIONS: The operon containing
      magA is responsible for capsular serotype K1 of K. pneumoniae. Several loci in
      the operon are unique determinants of K1 strains.

PMID- 16453260
TI  - Human leukocyte antigen haplotypes in the genetic control of immune response to
      measles-mumps-rubella vaccine.
AB  - To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and
      their genotypic combinations to immune status after measles-mumps-rubella (MMR)
      vaccination, 346 children 12-18 years of age were studied. The class I A*29-Cw*16
      B*44 haplotype was associated with lower levels of immunoglobulin G (IgG)
      antibody to both measles (P=.08) and mumps (P=.03) viral antigens. The A*26-Cw*12
      B*38 haplotype was associated with higher cellular immune responses to measles
      (P=.02) and mumps (P=.01) vaccine viruses. Subjects with the class II DRB1*03
      DQB1*02-DPB1*04 haplotype had higher lymphoproliferative responses to measles
      virus (P=.01) and mumps virus (P=.006). The DRB1*15/16-DQB1*06-DPB1*03 haplotype
      was associated with high levels of IgG antibody to measles virus (P=.09) but low
      levels of IgG antibody to rubella virus (P=.02), whereas DRB1*04-DQB1*03-DPB1*03
      was associated with high lymphoproliferative responses to both measles (P=.01)
      and rubella (P=.002) vaccine viruses. A*26-Cw*12-B*38 was associated with both
      mumps virus-specific humoral (P=.007) and cell-mediated (P=.01) immune responses
      after 2 doses of MMR vaccine. Haplotype DRB1*04-DQB1*03-DPB1*03 was associated
      with both lower rubella virus IgG antibody levels (P=.02) and higher rubella
      virus-specific lymphoproliferation (P=.002). Better characterization of such HLA
      profiles could inform and improve the design of novel epitope-rich vaccines and
      help to predict protective immune responses at the individual and population
      level.

PMID- 16453262
TI  - High serum hepatitis C virus (HCV) RNA load predicts the presence of HCV RNA in
      saliva from individuals with chronic and acute HCV infection.
AB  - The detection of hepatitis C virus (HCV) in saliva was studied. Twenty-three
      subjects with chronic HCV infection and 1 subject with acute HCV infection were
      enrolled in a 21-day study. Roche COBAS Amplicor and Bayer VERSANT HCV RNA
      qualitative assays were used. For the 23 subjects with chronic HCV infection, 72%
      of 474 saliva samples were positive (or were imputed to be positive) for HCV RNA.
      Serum HCV RNA load predicted the detection of HCV RNA in saliva (odds ratio of
      378.7 [95% confidence interval, 18.9-9996.6] for each additional log10 value).
      This association was also observed in 1 subject with acute HCV infection. Thus,
      our data demonstrate that salivary HCV RNA detection was associated with serum
      HCV RNA load in individuals who were chronically or acutely infected with HCV.

PMID- 16453261
TI  - Prolonged illness after infectious mononucleosis is associated with altered
      immunity but not with increased viral load.
AB  - BACKGROUND: Primary Epstein-Barr virus (EBV) infection causes a spectrum of
      characteristics that range from asymptomatic seroconversion to severe infectious
      mononucleosis (IM), sometimes with prolonged symptoms and disability. We examined
      the relationships between clinical course, number of viral copies, and
      immunological parameters in a prospective cohort of subjects with recent IM.
      METHODS: Eight case patients with at least 6 months of disabling symptoms and 31
      matched control subjects who had recovered promptly were included. Symptom scores
      were recorded at regular intervals over the course of 12 months. Cellular EBV
      load, EBV-specific antibody responses, lymphocyte subsets, and EBV-specific
      interferon (IFN)- gamma induction were measured. RESULTS: In case patients with
      prolonged illness, the severity of acute-phase symptoms was greater, the
      development of anti-EBV nuclear antigen-1 immunoglobulin G was more rapid, and
      the time to development of the peak IFN- gamma response to the majority of latent
      cycle EBV peptides was generally slower than those in control subjects. However,
      in both groups, neither viral nor immune parameters correlated with the severity
      or duration of symptoms. CONCLUSIONS: The resolution of symptomatic IM is not
      determined by control of viremia, nor is it easily explained by altered host
      responses to EBV infection. The detailed determinants of delayed recovery remain
      to be elucidated.

PMID- 16453263
TI  - Live attenuated influenza vaccine is safe and immunogenic in immunocompromised
      ferrets.
AB  - Patients undergoing chemotherapy for cancer are highly susceptible to influenza
      virus infection. Prevention of influenza virus infection is complicated in the
      immunocompromised host because of suboptimal responses to the trivalent
      inactivated influenza vaccine (TIV). A new, live attenuated influenza vaccine
      (LAIV; FluMist) may offer a more effective alternative to TIV, but the safety of
      this LAIV in immunocompromised patients must first be established. In the present
      study, FluMist was administered to ferrets immunocompromised by treatment with
      dexamethasone and cytarabine. Ferrets exhibited no signs or symptoms attributable
      to FluMist, and nasal clearance of LAIV strains from immunocompromised ferrets
      was similar to that from control ferrets. Serum antibody responses against the
      vaccinating strains were analyzed as a measure of vaccine efficacy. Antibody
      titers to all 3 vaccine strains in immunocompromised ferrets were similar to
      those seen in mock-treated control ferrets, as assessed by microneutralization
      assay. These findings support the potential use of this vaccine in
      immunocompromised humans.

PMID- 16453264
TI  - Therapy with a severe acute respiratory syndrome-associated coronavirus
      neutralizing human monoclonal antibody reduces disease severity and viral burden
      in golden Syrian hamsters.
AB  - BACKGROUND: Immunotherapy with monoclonal antibodies (MAbs) offers safe
      interventions for the prevention of infection in patients after organ
      transplantation and for the treatment of cancers and autoimmune diseases. MAb 201
      is a severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-specific
      MAb that prevents establishment of viral replication in vitro and prevents viral
      replication in vivo when administered prophylactically. The efficacy of MAb 201
      in the treatment of SARS was evaluated in golden Syrian hamsters, an animal model
      that supports SARS-CoV replication to high levels and displays severe
      pathological changes associated with infection, including pneumonitis and
      pulmonary consolidation. METHODS: Golden Syrian hamsters that were intranasally
      inoculated with SARS-CoV were treated with various doses of MAb 201 or an
      irrelevant MAb 24 h after inoculation. Two to 7 days after infection, the
      hamsters were killed, and their lungs were collected for evaluation of viral
      titers and pathological findings. RESULTS: Postexposure treatment with MAb 201
      can alleviate the viral burden and associated pathological findings in a golden
      Syrian hamster model of SARS-CoV infection. After a hamster is treated with MAb
      201, its viral burden is reduced by 102.4-103.9 50% tissue-culture infectious
      doses per gram of tissue, and the severity of associated pathological findings,
      including interstitial pneumonitis and consolidation, is also remarkably reduced.
      CONCLUSIONS: The demonstration of successful postexposure MAb 201 therapy in an
      animal model that demonstrates viral replication and associated pulmonary
      pathological findings suggests that MAb 201 may be useful in the arsenal of tools
      to combat SARS.

PMID- 16453265
TI  - Normal CD16 expression and phagocytosis of Mycobacterium avium complex by
      monocytes from a current cohort of HIV-1-infected patients.
AB  - Monocyte phenotype and function were measured in whole blood sampled from a
      current cohort of human immunodeficiency virus (HIV)-infected individuals
      attending a large, metropolitan, university-affiliated hospital. There was no
      significant difference in the prevalence of CD16+ monocytes or the capacity of
      monocytes to ingest heat-killed Mycobacterium avium complex between these
      individuals and HIV-uninfected control subjects, regardless of viral load,
      current CD4+ T cell count, nadir CD4+ T cell count, or time since diagnosis of
      HIV infection. CD16+ monocyte prevalence was, however, elevated in patients not
      currently receiving antiretroviral therapy. We conclude that HIV type 1 infection
      in the setting of highly active antiretroviral therapy is associated with normal
      monocyte function and phenotype.

PMID- 16453266
TI  - Repeat-region polymorphisms in the gene for the dendritic cell-specific
      intercellular adhesion molecule-3-grabbing nonintegrin-related molecule: effects
      on HIV-1 susceptibility.
AB  - In 1716 individuals--801 human immunodeficiency virus (HIV)-1-seropositive
      individuals, 217 high-risk HIV-1-seronegative individuals, and 698 general HIV-1
      seronegative individuals--from a Seattle cohort and a Multicenter AIDS Cohort
      Study cohort, the association between HIV-1 susceptibility and repeat-region
      polymorphisms in the gene for the dendritic cell-specific intercellular adhesion
      molecule-3-grabbing nonintegrin-related molecule (DC-SIGNR) was investigated; 16
      genotypes were found in the DC-SIGNR repeat region. The DC-SIGNR homozygous 7/7
      repeat was found to be associated with an increased risk of HIV-1 infection
      (17.5% in high-risk HIV-1-seronegative individuals vs. 28.5% in HIV-1
      seropositive individuals; P=.0015), whereas the DC-SIGNR heterozygous 7/5 repeat
      tended to be correlated with resistance to HIV-1 infection (35.5% in high-risk
      HIV-1-seronegative individuals vs. 27.6% in HIV-1-seropositive individuals;
      P=.0291). These findings suggest that DC-SIGNR polymorphisms may influence
      susceptibility to HIV-1.

PMID- 16453267
TI  - Premature induction of an immunosuppressive regulatory T cell response during
      acute simian immunodeficiency virus infection.
AB  - Here we report the results of an investigation into the possibility that one
      mechanism responsible for the establishment of persistent human immunodeficiency
      virus infection is an early regulatory T (Treg) cell response that blunts virus
      specific responses. Using the simian immunodeficiency virus (SIV)-infected rhesus
      macaque model, we show that, indeed, viral replication and immune activation in
      lymphatic tissue drive a premature immunosuppressive response, with dramatic
      increases in the frequencies of CD4+CD25+FOXP3+ Treg cells, transforming growth
      factor- beta 1+ cells, interleukin-10+ cells, and indoleamine 2,3
      dioxygenase+CD3+ cells. When we compared SIV infection with rhesus
      cytomegalovirus (RhCMV) infection, we found that the frequency of Treg cells
      paralleled the magnitude of immune activation during both infections but that the
      magnitude of immune activation and of the Treg cell response were lower and
      peaked much later during RhCMV infection. Importantly, the frequency of Treg
      cells inversely correlated with the magnitude of the SIV-specific cytotoxic T
      lymphocyte response. We conclude that an early Treg cell response during acute
      SIV infection may contribute to viral persistence by prematurely limiting the
      antiviral immune response before infection is cleared.

PMID- 16453268
TI  - Dynamics of anti-VAR2CSA immunoglobulin G response in a cohort of senegalese
      pregnant women.
AB  - BACKGROUND: Pregnancy-associated malaria (PAM) is precipitated by the
      accumulation of parasites in the placental intervillous spaces and causes
      maternal anemia and low birth weight. In PAM, placental parasites adhere to
      chondroitin sulfate A (CSA) through a unique set of variant surface antigens
      (VSAPAM). Several studies have shown that 1 var gene, var2csa, is transcribed at
      high levels and expressed in CSA-binding Plasmodium falciparum parasites.
      METHODS: Plasma levels of anti-VAR2CSA immunoglobulin G (IgG) in Senegalese women
      were measured during pregnancy by enzyme-linked immunosorbent assay, using 3
      recombinant proteins representing 3 domains of the var2csa gene product. RESULTS:
      The 3 recombinant proteins were specifically recognized by plasma from pregnant
      women but not by control plasma. A parity-dependent recognition pattern was
      observed with 2 of the 3 VAR2CSA antigens. A kinetic study demonstrated that a
      single P. falciparum infection was able to trigger a VAR2CSA-specific antibody
      response. Among women with infected placentas, women with high anti-VAR2CSA IgG
      levels at enrollment were more likely to present with a past infection than with
      an acute/chronic infection. CONCLUSIONS: Anti-VAR2CSA IgGs are involved in
      clinical protection against pregnancy-associated malaria and strengthens the hope
      for making a VAR2CSA-based vaccine.

PMID- 16453269
TI  - Antigenic differences and conservation among placental Plasmodium falciparum
      infected erythrocytes and acquisition of variant-specific and cross-reactive
      antibodies.
AB  - Background. Pregnant women are infected by Plasmodium falciparum with novel
      antigenic phenotypes that adhere to chondroitin sulfate A (CSA) and other
      receptors in the placenta. The diverse and variant parasite protein P. falciparum
      erythrocyte membrane protein 1 (PfEMP1), which is encoded by var genes, is a
      ligand for CSA and a major target of antibodies associated with protective
      immunity.Methods. Serum samples from pregnant women exposed to malaria were
      tested for immunoglobulin G, adhesion-inhibitory antibodies, and agglutinating
      antibodies to different CSA-binding isolates expressing conserved var2csa-type
      genes and to parasite isolates from infected placentas. Parasite isolates also
      were examined to assess PfEMP1 expression, the effect of trypsin treatment of
      infected erythrocytes on parasite adhesion and cleavage of PfEMP1, and inhibition
      of adhesion by rabbit antiserum raised against a CSA-binding isolate.Results.
      Findings demonstrated that (1) there are significant antigenic differences
      between CSA-binding isolates that correspond with polymorphisms in var2csa; (2)
      there are differences in the properties of PfEMP1 and antibody reactivity between
      CSA-binding and placental isolates, which express multiple PfEMP1 forms; (3)
      acquired antibodies target diverse and cross-reactive epitopes expressed by CSA
      binding infected erythrocytes, and cross-reactive antibodies are not necessarily
      cross-inhibitory; and (4) the breadth of antibody reactivity is greater among
      multigravidae than among primigravidae.Conclusions. Immunity may be mediated by a
      repertoire of antibodies to diverse and common epitopes. Strategies based on
      vaccination with a single domain or isolate might be hindered by antigenic
      diversity.

PMID- 16453270
TI  - Immunization of Aotus monkeys with recombinant cysteine-rich interdomain region 1
      alpha protects against severe disease during Plasmodium falciparum reinfection.
AB  - BACKGROUND: After continuous exposure to malarial infections in regions of Africa
      where malaria is hyperendemic, children attain clinical immunity. This immunity
      results, in part, from the acquisition of antibodies against a large repertoire
      of variant antigens expressed on the surface of infected erythrocytes, such as
      the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). We determined
      whether a subunit vaccine to a portion of PfEMP1 could induce protection in
      nonhuman primates. METHODS: We immunized Aotus nancymai monkeys with PfEMP1
      recombinant (r) cysteine-rich interdomain region 1 alpha (CIDR1 alpha ) and
      infected them twice with P. falciparum Vietnam Oak Knoll strain, the most
      virulent strain of P. falciparum in Aotus monkeys--each infection expressed a
      different PfEMP1. Anti-PfEMP1 antibodies were analyzed by enzyme-linked
      immunosorbent assay against rCIDR1 alpha and by flow cytometry against infected
      erythrocytes. RESULTS: Immunization with rCIDR1 alpha was not protective, despite
      delayed patency during the first infection, but it protected monkeys against
      severe anemia during reinfection. Protection against anemia is associated with a
      more rapid increase in antibodies to PfEMP1. CONCLUSION: The findings of reduced
      severe disease in rCIDR1 alpha -vaccinated Aotus monkeys provide experimental
      support for a PfEMP1-based vaccine to protect African children against severe
      malarial disease. Such vaccination may function by priming for the accelerated
      acquisition of immunity to new PfEMP1 variants.

PMID- 16453271
TI  - Prospective evaluation of a polymerase chain reaction-ELISA targeted to
      Aspergillus fumigatus and Aspergillus flavus for the early diagnosis of invasive
      aspergillosis in patients with hematological malignancies.
AB  - BACKGROUND: Current laboratory and radiological methods for diagnosis of invasive
      aspergillosis (IA) lack sensitivity and specificity. METHODS: We prospectively
      evaluated the diagnostic value of twice-weekly screening for circulating
      Aspergillus fumigatus and A. flavus DNA with a polymerase chain reaction-enzyme
      linked immunosorbent assay (PCR-ELISA). RESULTS: Among the 201 adult patients
      with hematological malignancies who were included in the study, 55 IA cases were
      diagnosed. On the basis of the analysis of 1205 serum samples from 167 patients,
      the sensitivity, specificity, and positive and negative predictive values of the
      PCR-ELISA for proven and probable IA cases were 63.6%, 89.7%, 63.6%, and 89.7%,
      respectively, when samples with 2 consecutive positive results were used. The use
      of a combination of the PCR-ELISA and a galactomannan (GM) assay increased the
      sensitivity to 83.3%, increased the negative predictive value to 97.6%, and
      decreased the specificity to 69.8%. In most patients with IA, PCR-ELISA
      positivity anticipated or was simultaneous with the initiation of antifungal
      therapy, the abnormalities found by computed tomography, the
      mycological/histological diagnosis, and the GM positivity. Overall, 56.3% of the
      patients had at least 1 positive sample, and the false single-positive rate was
      44.8%. CONCLUSIONS: In addition to serial screening for GM antigenemia and
      radiological surveillance, PCR-ELISA may improve the rates of early diagnosis of
      IA and the management of patients with hematological malignancies.

PMID- 16453272
TI  - Association between serum cytokine profiles and schistosomiasis-related hepatic
      fibrosis: infection by Schistosoma japonicum versus S. mansoni.

PMID- 16453275
TI  - The xyloglucan-cellulose assembly at the atomic scale.
AB  - The assembly of cell wall components, cellulose and xyloglucan (XG), was
      investigated at the atomistic scale using molecular dynamics simulations. A
      molecular model of a cellulose crystal corresponding to the allomorph Ibeta and
      exhibiting a flexible complex external morphology was employed to mimic the
      cellulose microfibril. The xyloglucan molecules considered were the three typical
      basic repeat units, differing only in the size of one of the lateral chain. All
      the investigated XG fragments adsorb nonspecifically onto cellulose fiber;
      multiple arrangements are equally probable, and every cellulose surface was
      capable of binding the short XG molecules. The following structural effects
      emerged: XG molecules that do not have any long side chains tended to adapt
      themselves nicely to the topology of the microfibril, forming a flat,
      outstretched conformation with all the sugar residues interacting with the
      surface. In contrast, the XG molecules, which have long side chains, were not
      able to adopt a flat conformation that would enable the interaction of all the XG
      residues with the surface. In addition to revealing the fundamental atomistic
      details of the XG adsorption on cellulose, the present calculations give a
      comprehensive understanding of the way the XG molecules can unsorb from cellulose
      to create a network that forms the cell wall. Our revisited view of the
      adsorption features of XG on cellulose microfibrils is consistent with
      experimental data, and a model of the network is proposed.

PMID- 16453274
TI  - In vivo localization and identification of the antiplasmodial alkaloid
      dioncophylline A in the tropical liana Triphyophyllum peltatum by a combination
      of fluorescence, near infrared Fourier transform Raman microscopy, and density
      functional theory calculations.
AB  - Near infrared Fourier transform (NIR FT) micro Raman spectroscopy in combination
      with density functional theory (DFT) calculations has been applied for an in vivo
      localization of the antiplasmodial naphthylisoquinoline alkaloid dioncophylline A
      (1) in the tropical liana Triphyophyllum peltatum. Fluorescence microscopy images
      suggest finding this active agent in 10 mum big inclusions located in the cortex
      of the stem or the beginning of the leaves. By means of spatially resolved FT
      Raman micro spectroscopy, we could detect dioncophylline A (1) in these
      inclusions. FT Raman spectroscopy is an extremely selective tool capable of
      differentiating between various structurally similar naphthylisoquinoline
      alkaloids. With the help of DFT calculations, we succeeded in assigning the
      differences found in the FT Raman spectra of the various naphthylisoquinolines to
      nuC=C vibrations of the naphthyl ring. The presented results are of relevance for
      the investigation and extraction of new antimalarial active agents.

PMID- 16453276
TI  - Average assignment method for predicting the stability of protein mutants.
AB  - Prediction of protein stability upon amino acid substitutions is an important
      problem in molecular biology and it will be helpful for designing stable mutants.
      In this work, we have analyzed the stability of protein mutants using three
      different data sets of 1791, 1396, and 2204 mutants, respectively, for thermal
      stability (DeltaTm), free energy change due to thermal (DeltaDeltaG), and
      denaturant denaturations (DeltaDeltaGH2O), obtained from the ProTherm database.
      We have classified the mutants into 380 possible substitutions and assigned the
      stability of each mutant using the information obtained with similar type of
      mutations. We observed that this assignment could distinguish the stabilizing and
      destabilizing mutants to an accuracy of 70-80% at different measures of
      stability. Further, we have classified the mutants based on secondary structure
      and solvent accessibility (ASA) and observed that the classification
      significantly improved the accuracy of prediction. The classification of mutants
      based on helix, strand, and coil distinguished the stabilizing/destabilizing
      mutants at an average accuracy of 82% and the correlation is 0.56; information
      about the location of residues at the interior, partially buried, and surface
      regions of a protein correctly identified the stabilizing/destabilizing residues
      at an average accuracy of 81% and the correlation is 0.59. The nine
      subclassifications based on three secondary structures and solvent
      accessibilities improved the accuracy of assigning stabilizing/destabilizing
      mutants to an accuracy of 84-89% for the three data sets. Further, the present
      method is able to predict the free energy change (DeltaDeltaG) upon mutations
      within a deviation of 0.64 kcal/mol. We suggest that this method could be used
      for predicting the stability of protein mutants.

PMID- 16453277
TI  - Off-line combination of reversed-phase liquid chromatography and laser
      desorption/ionization time-of-flight mass spectrometry with seamless post-source
      decay fragment ion analysis for characterization of square-planar nickel(II)
      complexes.
AB  - Characterization of square-planar nickel(II) complexes of the Schiff base of (S)
      N-benzylproline (2-benzoylphenyl)amide and various amino acids that are used as
      efficient alpha-amino acids synthons was carried out using laser
      desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) in off-line
      combination with liquid chromatography. A mixture of four square-planar
      nickel(II) complexes was separated using reversed-phase liquid chromatography
      (RPLC) and the separated fractions from the chromatographic run were spotted on
      the metal target directly from the column outlet using a lab-made sample
      deposition device. The separated fractions were then analyzed by LDI-TOF MS.
      Seamless postsource decay (sPSD) fragment ion analysis was used for their
      structural characterization, which made possible the confirmation of expected
      chemical structures of the analyzed compounds. The off-line combination of the
      separation by RPLC and analysis by LDI-TOF MS allowed successful separation,
      sensitive detection and structure elucidation of the square-planar nickel(II)
      complexes.

PMID- 16453278
TI  - Expression of DNMT3A transcripts and nucleolar localization of DNMT3A protein in
      human testicular and fibroblast cells suggest a role for de novo DNA methylation
      in nucleolar inactivation.
AB  - Transcriptional silencing during differentiation of human male germ cells and
      serum starvation of human fibroblasts is controlled by epigenetic mechanisms that
      involve de novo DNA methylation. It is associated with high expression of
      different transcripts of the DNA methyltransferase 3A (DNMT3A) gene that encode
      two isoforms with de novo methyltransferase activity and one without catalytic
      activity. Western blots revealed that DNMT3A protein (with catalytic domain) is
      present at low levels in several tissues and at increased levels in testicular
      cells and growth-arrested fibroblasts. Immunofluorescence experiments localized
      DNMT3A to discrete nucleolar foci in B spermatogonia and resting fibroblasts. The
      data here suggest a role for de novo DNA methylation in nucleolar inactivation.

PMID- 16453279
TI  - Functional and structural properties of stannin: roles in cellular growth,
      selective toxicity, and mitochondrial responses to injury.
AB  - Stannin (Snn) was discovered using subtractive hybridization methodology designed
      to find gene products related to selective organotin toxicity and apoptosis. The
      cDNAs for Snn were first isolated from brain tissues sensitive to trimethyltin,
      and were subsequently used to localize, characterize, and identify genomic DNA,
      and other gene products of Snn. Snn is a highly conserved, 88 amino acid protein
      found primarily in vertebrates. There is a minor divergence in the C-terminal
      sequence between amphibians and primates, but a nearly complete conservation of
      the first 60 residues in all vertebrates sequenced to date. Snn is a membrane
      bound protein and is localized, in part, to the mitochondria and other vesicular
      organelles, suggesting that both localization and conservation are significant
      for the overall function of the protein. The structure of Snn in a micellar
      environment and its architecture in lipid bilayers have been determined using a
      combination of solution and solid-state NMR, respectively. Snn structure
      comprised a single transmembrane domain (residues 10-33), a 28-residue linker
      region from residues 34-60 that contains a conserved CXC metal binding motif and
      a putative 14-3-3xi binding region, and a cytoplasmic helix (residues 61-79),
      which is partially embedded into the membrane. Of primary interest is
      understanding how this highly-conserved peptide with an interesting structure and
      cellular localization transmits both normal and potentially toxic signals within
      the cell. Evidence to date suggests that organotins such as trimethyltin interact
      with the CXC region of Snn, which is vicinal to the putative 14-3-3 binding site.
      In vitro transfection analyses and microarray experiments have inferred a
      possible role of Snn in several key signaling systems, including activation of
      the p38-ERK cascade, p53-dependent pathways, and 14-3-3xi protein-mediated
      processes. TNFalpha can induce Snn mRNA expression in endothelial cells in a PKC
      epsilon dependent manner. Studies with Snn siRNA suggest that this protein may be
      involved in growth regulation, since inhibition of Snn expression alone leads to
      reduced endothelial cells growth and induction of COP-1, a negative regulator of
      p53 function. A key piece of the puzzle, however, is how and why such a highly
      conserved protein, localized to mitochondria, interacts with other regulatory
      proteins to alter growth and apoptosis. By knowing the structure, location, and
      possible signaling pathways involved, we propose that Snn constitutes an
      important sensor of mitochondrial damage, and plays a key role in the mediation
      of cross-talk between mitochondrial and nuclear compartments in specific cell
      types.

PMID- 16453280
TI  - Analysis of fungal cyclopentenone derivatives from Hygrophorus spp. by liquid
      chromatography/electrospray-tandem mass spectrometry.
AB  - Fruitbodies of the genus Hygrophorus (Basidiomycetes) contain a series of anti
      biologically active compounds. These substances named hygrophorones possess a
      cyclopentenone skeleton. LC/ESI-MS/MS presents a valuable tool for the
      identification of such compounds. The mass spectral behaviour of typical selected
      members of this group under positive and negative ion electrospray conditions is
      discussed. Using the ESI collision-induced dissociation (CID) mass spectra of the
      [M + H]+ and [M - H]- ions, respectively, the compounds can be classified with
      respect to the substitution pattern at the cyclopentenone ring and the type of
      oxygenation at C-6 (hydroxy/acetoxy or oxo function) of the side chain. The
      elemental composition of the fragment ions was determined by ESI-QqTOF
      measurements. Thus, in case of the negative ion CID mass spectra an unusual loss
      of CO2 from the deprotonated molecular ions could be observed.

PMID- 16453281
TI  - Role of AP1 element in the activation of human eNOS promoter by
      lysophosphatidylcholine.
AB  - Human endothelial nitric oxide synthase (eNOS) plays a crucial role in
      maintaining blood pressure homeostasis and vascular integrity. It, therefore, is
      very essential to elucidate the regulation of it. In the current study, a red
      fluorescent protein (RFP) reporter system containing human eNOS promoter was
      first constructed, being characteristics of real time morphologic and
      quantitative analysis for the same sample. It was observed by DNA sequence
      deletion that 68% of the basal activity of the promoter was controlled by the
      region from -1 to -166 bp, and 32% of it was dependent on the region from -1,033
      to -1,600 bp. The mutation of SSRE element (-999 to -994 bp) and wild-type SSRE
      decoy oligodeoxynucleotides (ODN) did not alter the basal activity and the
      stimulating activity by lysophosphatidylcholine (LPC). The mutation of upstream
      AP1 element (-1,530 to -1,524 bp) did not affect the basal activity, but resulted
      in near 30% reduction in the stimulating activity by LPC. Moreover, wild-type AP1
      decoy ODN also remarkably attenuated it. It was proved by EMSA analysis that LPC
      indeed enhanced the activity of AP1 transcriptional factor binding to AP1
      element. However, the role of AP1 was dependent on the presence of SP1, which was
      proved by the combining mutation of AP1 with SP1. The mutation of downstream AP1
      element (-662 to -656 bp) had no influence on the basal and stimulating
      activities by LPC. These results strongly suggest that the main functional region
      of the promoter is from -1 bp to -166 bp, that the upstream AP1 participates in
      the activation of the promoter by LPC on the premise of the presence of SP1, and
      that the downstream AP1 and SSRE do not involve the basal and stimulating
      activity by LPC.

PMID- 16453282
TI  - The American College of Rheumatology response criteria for proliferative and
      membranous renal disease in systemic lupus erythematosus clinical trials.

PMID- 16453283
TI  - CD28-dependent differentiation into the effector/memory phenotype is essential
      for induction of arthritis in interleukin-1 receptor antagonist-deficient mice.
AB  - OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra)-deficient mice on a BALB/c
      background spontaneously develop a chronic inflammatory polyarthropathy closely
      resembling that of rheumatoid arthritis in humans. To elucidate the role of CD28
      costimulatory signals in the development of this disease, we studied IL-1Ra/CD28
      double-deficient mice. METHODS: We crossed IL-1Ra-deficient mice with CD28
      deficient mice and observed the incidence and severity of arthritis. To
      investigate functions of IL-1Ra/CD28-double-deficient T cells, cells were
      stimulated with CD3 monoclonal antibody or allogeneic antigen-presenting cells
      (APCs) and their proliferative responses and levels of cytokine production were
      measured. RESULTS: Disease severity was lower in IL-1Ra/CD28-double-deficient
      mice than in mice that were deficient only in IL-1Ra, although incidence of
      arthritis was not affected by the presence or absence of CD28. When pathogenic IL
      1Ra-KO T cells were transferred into nude mice, severe arthritis developed. Even
      though T cells from double-deficient mice showed the same diminished
      proliferative capacity as was seen in T cells from CD28-single-deficient animals,
      nude mice into which double-deficient T cells were transferred never developed
      arthritis. CONCLUSION: These findings indicate that IL-1Ra/CD28-double-deficient
      T cells can be activated by IL-1Ra-deficient activated APCs, resulting in
      induction of arthritis; however, these T cells did not induce the disease under
      normal conditions, because they did not differentiate into effector/memory
      phenotype.

PMID- 16453284
TI  - Reproducible genetic associations between candidate genes and clinical knee
      osteoarthritis in men and women.
AB  - OBJECTIVE: Osteoarthritis (OA) is recognized to have a genetic component, and in
      this study, we aimed to replicate in a case-control study of men and women with
      clinical knee OA genetic associations in 12 candidate genes previously reported
      to be associated with OA. METHODS: Twenty-five single-nucleotide polymorphisms
      were genotyped in 298 men and 305 women ages 50-86 who were diagnosed as having
      knee OA, as assessed both clinically and radiographically, and in 297 men and 299
      women matched for age and ethnicity (controls). Standardized anteroposterior
      radiographs of the knee in extension were performed on each of the cases, and all
      cases met the American College of Rheumatology criteria for OA of the knee.
      Genotype and haplotype frequencies in cases and controls were compared separately
      in men and women. The 12 genes tested were AACT, ADAM12, BMP2, CD36, CILP, COX2,
      ESR1, NCOR2, OPG, TNA, TNFAIP6, and VDR. RESULTS: Eight of the candidate genes
      were associated in women and 5 in men, and only 3 genes (TNFAIP6, NCOR2, and
      CD36) were not significantly associated in either sex. The strongest associations
      in terms of odds ratios (ORs) were a haplotype in ADAM12 (OR 7.1 [95% confidence
      interval (95% CI) 3.3-33.8]) and a haplotype in ESR1 (OR 3.6 [95% CI 1.18-10.98])
      in women. The same ADAM12 haplotype (OR 2.54 [95% CI 1.2-5.4]) and a haplotype in
      the CILP gene (OR 0.38 [95% CI 0.23-0.62]) were the strongest associations in
      men. CONCLUSION: We found that genes previously identified by their association
      with subclinical features of knee OA or progression were also associated with
      clinical knee OA. These genetic associations may identify individuals at a
      particularly high risk of developing knee OA.

PMID- 16453285
TI  - The role of folate receptor alpha in cancer development, progression and
      treatment: cause, consequence or innocent bystander?
AB  - Folate receptor alpha (FRalpha) is a membrane-bound protein with high affinity
      for binding and transporting physiologic levels of folate into cells. Folate is a
      basic component of cell metabolism and DNA synthesis and repair, and rapidly
      dividing cancer cells have an increased requirement for folate to maintain DNA
      synthesis, an observation supported by the widespread use of antifolates in
      cancer chemotherapy. FRalpha levels are high in specific malignant tumors of
      epithelial origin compared to normal cells, and are positively associated with
      tumor stage and grade, raising questions of its role in tumor etiology and
      progression. It has been suggested that FRalpha might confer a growth advantage
      to the tumor by modulating folate uptake from serum or by generating regulatory
      signals. Indeed, cell culture studies show that expression of the FRalpha gene,
      FOLR1, is regulated by extracellular folate depletion, increased homocysteine
      accumulation, steroid hormone concentrations, interaction with specific
      transcription factors and cytosolic proteins, and possibly genetic mutations.
      Whether FRalpha in tumors decreases in vivo among individuals who are folate
      sufficient, or whether the tumor's machinery sustains FRalpha levels to meet the
      increased folate demands of the tumor, has not been studied. Consequently, the
      significance of carrying a FRalpha-positive tumor in the era of folic acid
      fortification and widespread vitamin supplement use in countries such as Canada
      and the United States is unknown. Epidemiologic and clinical studies using human
      tumor specimens are lacking and increasingly needed to understand the role of
      environmental and genetic influences on FOLR1 expression in tumor etiology and
      progression. This review summarizes the literature on the complex nature of FOLR1
      gene regulation and expression, and suggests future research directions.

PMID- 16453287
TI  - Hepatocyte growth factor and the Met system as a mediator of tumor-stromal
      interactions.
AB  - Crosstalk between carcinoma cells and host stromal cells such as fibroblasts has
      a great deal of influence on the invasive and metastatic behavior of cancer
      cells. The oncogenic action of fibroblasts has been demonstrated through genetic
      alterations that occur specifically in fibroblasts. Hepatocyte growth factor
      (HGF), a ligand for the Met receptor tyrosine kinase, plays a definitive role,
      particularly in the progression to invasive and metastatic cancers, predominantly
      as a stroma-derived paracrine mediator. Many types of cancer cells secrete
      molecules that enhance HGF production in fibroblasts, while fibroblast-derived
      HGF, in turn, is a potent stimulator of the invasion of cancer cells. Fibroblast
      specific genetic alterations leading to an overexpression of HGF are associated
      with the development of epithelial neoplasia and invasive carcinoma. Strategies
      for targeting the HGF-Met axis are being pursued, in attempts to block the
      malignant behavior of cancers. In normal tissues, the HGF-Met axis plays diverse
      roles in organogenesis and in wound healing. The simile that "cancer is a never
      healing wound" appears to be pertinent here.

PMID- 16453286
TI  - Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein
      overexpression in both renal tumors and corresponding nontumorous renal tissues.
AB  - To evaluate the significance of altered DNA methylation during renal
      tumorigenesis, tumorous tissues (T) and corresponding nontumorous renal tissues
      (N) from 94 patients with renal tumors, and normal renal tissues (C) from 16
      patients without renal tumors were investigated. DNA methylation status on CpG
      islands of the p16, human MutL homologue 1 (hMLH1), von-Hippel Lindau (VHL) and
      thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT) -1, -2, -12, 
      25 and -31 clones and DNA methyltransferase (DNMT) 1 expression were examined by
      bisulfite modification and immunohistochemistry, respectively. The average number
      of methylated CpG islands was significantly higher in N than in C, and was even
      higher in T. The average number of methylated CpG islands in N was significantly
      correlated with a higher histological grade of corresponding conventional renal
      cell carcinomas (RCCs). The average number of methylated CpG islands in RCCs was
      significantly correlated with macroscopic configuration with extranodular or
      multinodular growth, higher histological grade, infiltrating growth pattern and
      vascular involvement. The recurrence-free survival rate of patients with RCCs
      showing accumulation of DNA methylation was significantly lower than that of
      patients not showing this feature. The incidence of nuclear immunoreactivity for
      DNMT1 tended to be higher in proximal tubules from N than in those from C, and
      was significantly higher in RCCs. From the viewpoint of altered DNA methylation,
      N is at the precancerous stage, and N showing accumulation of DNA methylation may
      generate more malignant RCCs. Regional DNA hypermethylation may be associated
      with renal tumorigenesis from a precancerous condition to malignant progression
      and become a predictor of patient prognosis.

PMID- 16453288
TI  - Overexpression of caveolin-1 results in increased plasma membrane targeting of
      glycolytic enzymes: the structural basis for a membrane associated metabolic
      compartment.
AB  - Although membrane-associated glycolysis has been observed in a variety of cell
      types, the mechanism of localization of glycolytic enzymes to the plasma membrane
      is not known. We hypothesized that caveolin-1 (CAV-1) serves as a scaffolding
      protein for glycolytic enzymes and may play a role in the organization of cell
      metabolism. To test this hypothesis, we over-expressed CAV-1 in cultured A7r5
      (rat aorta vascular smooth muscle; VSM) cells. Confocal immunofluorescence
      microscopy was used to study the distribution of phosphofructokinase (PFK) and
      CAV-1 in the transfected cells. Areas of interest (AOI) were analyzed in a
      central Z-plane across the cell transversing the perinuclear region. To quantify
      any shift in PFK localization resulting from CAV-1 over-expression, we calculated
      a periphery to center (PC) index by taking the average of the two outer AOIs from
      each membrane region and dividing by the central one or two AOIs. We found the PC
      index to be 1.92 +/- 0.57 (mean +/- SEM, N = 8) for transfected cells and 0.59 +/
      0.05 (mean +/- SEM, N = 11) for control cells. Colocalization analysis
      demonstrated that the percentage of PFK associated with CAV-1 increased in
      transfected cells compared to control cells. The localization of aldolase (ALD)
      was also shifted towards the plasma membrane (and colocalized with PFK) in CAV-1
      over-expressing cells. These results demonstrate that CAV-1 creates binding sites
      for PFK and ALD that may be of higher affinity than those binding sites localized
      in the cytoplasm. We conclude that CAV-1 functions as a scaffolding protein for
      PFK, ALD and perhaps other glycolytic enzymes, either through direct interaction
      or accessory proteins, thus contributing to compartmented metabolism in vascular
      smooth muscle.

PMID- 16453289
TI  - Substrate specificity of soluble and membrane-associated ADP-ribosyltransferase
      ART2.1.
AB  - ADP-ribosyltransferases (ARTs) are a family of enzymes that catalyze the covalent
      transfer of an ADP-ribose moiety, derived from NAD, to an amino acid of an
      acceptor protein, thereby altering its function. To date, little information is
      available on the protein target specificity of different ART family members. ART2
      is a T-cell-specific transferase, attached to the cell surface by a
      glycosylphosphatidylinositol (GPI) anchor, and also found in serum. Here we
      investigated the role of ART2 localization in serum or on the cell surface, or
      solubilized with detergents or enzymes, on its target protein specificity. We
      found that detergent solubilization of cell membranes, or release of ART2 by
      phosphoinositide-specific phospholipase C treatment, altered the ability of ART2
      to ADP-ribosylate high or low molecular weight histone proteins. Similarly,
      soluble recombinant ART2 (lacking the GPI anchor) showed a different histone
      specificity than did cell-bound ART2. When soluble ART2 was incubated with serum
      proteins in the presence of [32P]-labeled NAD, several serum proteins were ADP
      ribosylated in a thiol-specific manner. Mass spectrometry of labeled proteins
      identified albumin and transferrin as ADP-ribosylated proteins in serum.
      Collectively, these studies reveal that the membrane or solution environment of
      ART2 plays a pivotal role in determining its substrate specificity.

PMID- 16453290
TI  - Study of in vivo differentiation of rat bone marrow stromal cells into schwann
      cell-like cells.
AB  - In order to raise an abundant and accessible reservoir for Schwann cells (SCs),
      which are used as seed cells for constructing tissue-engineered nerve grafts, we
      investigated the feasibilty of in vivo differentiation of bone marrow stromal
      cells (MSCs) into SC-like cells. In this study, MSCs were harvested from adult
      rats' bone marrow, culture-expanded, and characterized. Subcultured MSCs were
      then labeled with Hoechst 33342, followed by transplantation into the nerve
      regeneration chamber, which was made of a silicone tube bridging the sciatic
      nerve defect of the rats. Four weeks after surgery, some of the differentiated
      MSCs turned into SC-like cells immunopositive to S-100 protein, accompanied by
      myelination of the regenerated nerve fibers. Walking-track analyses provided
      evidence that transplantation of MSCs contributed to reconstruction of the
      sciatic nerve and reinnervation of target tissues. The experimental results
      suggest that MSCs are capable of differentiating into SC-like cells in vivo,
      making them a promising candidate for cell transplantation in peripheral nerve
      repair.

PMID- 16453291
TI  - Bayesian estimation of evoked and induced responses.
AB  - We describe an extension of our empirical Bayes approach to
      magnetoencephalography/electroencephalography (MEG/EEG) source reconstruction
      that covers both evoked and induced responses. The estimation scheme is based on
      classical covariance component estimation using restricted maximum likelihood
      (ReML). We have focused previously on the estimation of spatial covariance
      components under simple assumptions about the temporal correlations. Here we
      extend the scheme, using temporal basis functions to place constraints on the
      temporal form of the responses. We show how the same scheme can estimate evoked
      responses that are phase-locked to the stimulus and induced responses that are
      not. For a single trial the model is exactly the same. In the context of multiple
      trials, however, the inherent distinction between evoked and induced responses
      calls for different treatments of the underlying hierarchical multitrial model.
      We derive the respective models and show how they can be estimated efficiently
      using ReML. This enables the Bayesian estimation of evoked and induced changes in
      power or, more generally, the energy of wavelet coefficients.

PMID- 16453292
TI  - Influence of structure on the tissue dynamics of the human soleus muscle observed
      in MRI studies during isometric contractions.
AB  - This article investigates how the internal structure of muscle and its
      relationship with tendon and even skeletal structures influence the translation
      of muscle fiber contractions into movement of a limb. Reconstructions of the
      anatomy of the human soleus muscle from the Visible Human Dataset (available from
      the National Library of Medicine), magnetic resonance images (MRI), and cadaver
      studies revealed a complex 3D connective tissue structure populated with pennate
      muscle fibers. The posterior aponeurosis and the median septum of the soleus form
      the insertion of the muscle and are continuous with the Achilles tendon. The
      distal extremities of the pennate muscle fibers attach to these structures. The
      anterior aponeurosis is located intramuscularly, between the posterior
      aponeurosis and the median septum. It forms the origin of the muscle and contacts
      the proximal extremities of the soleus muscle fibers. MRI measurements of in vivo
      tissue velocities during isometric contractions (20% and 40% maximum voluntary
      contractions) revealed a similarly complex 3D distribution of tissue movements.
      The distribution of velocities was similar to the distribution of major
      connective tissue structures within the muscle. During an isometric contraction,
      muscle fiber contractions move the median septum and posterior aponeurosis
      proximally, relative to the anterior aponeurosis. The pennate arrangement of
      muscle fibers probably amplifies muscle fiber length changes but not sufficiently
      to account for the twofold difference in muscle fiber length changes relative to
      excursion of the calcaneus. The discrepancy may be accounted for by an additional
      gain mechanism operating directly on the Achilles tendon by constraining the
      posterior movement of the tendon, which would otherwise occur due to the
      increasingly posterior location of the calcaneus in plantarflexeion.

PMID- 16453293
TI  - Clinical images: Dysphagia is sometimes easier to swallow than spinal surgery.

PMID- 16453294
TI  - A murine model of mixed connective tissue disease induced with U1 small nuclear
      RNP autoantigen.
AB  - OBJECTIVE: To test whether immunizing mice with autoantigens closely linked to
      mixed connective tissue disease (MCTD) could induce an MCTD-like clinical
      syndrome distinguishable from systemic lupus erythematosus (SLE). METHODS:
      Transgenic and knockout C57BL/6-derived mice were immunized subcutaneously at age
      8-12 weeks with U1-70-kd small nuclear RNP (70K) fusion protein along with either
      Freund's complete adjuvant (CFA) or U1 RNA. After 2 months, mice were killed and
      analyzed histologically and serologically. RESULTS: Immunization of C57BL/6
      derived mice transgenic for human HLA-DR4 with 70K and either CFA or U1 RNA led
      to anti-70K antibodies in 62% of mice (21 of 34), and diversified anti-RNP immune
      responses. MCTD-like lung disease also developed in 50% of immunized mice (17 of
      34), and anti-70K antibodies were strongly correlated with lung disease. CFA and
      U1 RNA were comparably able to induce this syndrome. Mice deficient in Toll-like
      receptor 3 (TLR-3) also developed this same syndrome when immunized with 70K and
      CFA. However, TLR-3(-/-) mice failed to develop MCTD-like lung disease when
      treated with 70K and U1 RNA. Rather, TLR-3(-/-) mice immunized with 70K and U1
      RNA developed an autoimmune syndrome characterized by glomerulonephritis typical
      of SLE. CONCLUSION: Exposure to 70K in an appropriate context is sufficient to
      induce autoimmunity and target organ injury consistent with MCTD. This system
      represents a new model of autoimmune interstitial lung disease, and establishes a
      closer link between anti-70K immunity and MCTD-like lung disease. Of note,
      changes in innate immune signaling can cause the same trigger to lead to the
      development of SLE-like nephritis rather than MCTD-like lung disease.

PMID- 16453295
TI  - RepairNET: a bioinformatics toolbox for functional exploration of DNA damage
      response.
AB  - DNA damage response is one of the essential cellular mechanisms to maintaining
      the genomic integrity of the cell. Aberrations in the mechanism of DNA damage
      response often result in cancer. We describe here RepairNET, a protein-protein
      interaction network associated with the DNA damage response. RepairNET is
      assembled from the published literature by using a protocol that involved
      computational data mining of the MEDLINE and manual curation. This network
      represents the current knowledge on the intrinsic signaling pathways related to
      the DNA damage response process. RepairNET currently contains more than 1,200
      proteins with over 2,300 functional interactions. A number of web-interface tools
      have been implemented to facilitate a user-friendly environment. The users can
      navigate through the cellular network associated with the DNA damage response via
      a Java-based interactive graphical interface. In order to help users explore the
      functional relationships between the interacting proteins, we have assigned
      functional domains to the proteins in RepairNET based on their sequences. A total
      of 365 unique functional domains are assigned. RepairNET is available online at
      http://guanyin.chem.temple.edu/RepairNET.html. It could become an essential
      resource center for cancer research, providing clues to understanding the
      functional relationship between proteins in the network, and to building
      scientific models for the mechanism of DNA damage response and cancer
      proliferation.

PMID- 16453296
TI  - Peripheral neuropathy in an outpatient cohort of patients with Sjogren's
      syndrome.
AB  - Peripheral neuropathy is common in patients with Sjogren's syndrome (SS), but its
      precise prevalence is unknown. Most prior studies were conducted at neurology or
      rheumatology specialty clinics and likely selected for a more severely affected
      population. We evaluated 22 SS patients and 10 controls for evidence of
      neuropathy in an outpatient setting at a regional meeting of the Sjogren's
      Syndrome Foundation. We performed neurological examinations and nerve conduction
      studies (NCSs) and measured serum antinuclear antibody (ANA) and SS-A and SS-B
      antibody levels. Participants filled out a questionnaire pertaining to symptoms,
      diagnosis, and treatment. We found that signs and symptoms related to small axons
      were more common in patients with SS than in controls. Complaints of painful
      distal paresthesias in the feet were noted in 59% of patients but in only 10% of
      controls, and of abnormal sweating in 41% and 0%, respectively. Examination
      revealed decreased pinprick sensation in 64% of patients with SS, but in only 30%
      of controls. Overall, 45% of the patients but none of the controls were thought
      to have an isolated small-fiber neuropathy. Large-fiber dysfunction (as measured
      by testing vibration, deep tendon reflexes, and NCSs) was similar between the two
      groups. We conclude that small-fiber neuropathy is common in patients with SS.

PMID- 16453297
TI  - The old grey mare, she ain't what she used to be. Is she?: (commentary on Kaspers
      et al., page 539).

PMID- 16453298
TI  - Radiotherapy for life-threatening mediastinal hemangioma with Kasabach-Merritt
      syndrome.
AB  - Kasabach-Merritt Syndrome (KMS) originally referred to a hemangioma associated
      with life-threatening thrombocytopenia and a consumption coagulopathy. Treatment
      includes surgery, steroids, and alpha interferon. However response may be
      unsatisfactory and mortality rates of 10-37% have been reported. We report a case
      of a 4-month-old male whose disease had not responded to steroids and alpha
      interferon. He required ventilation, and his condition was deteriorating. It was
      thought that he would probably die of his condition. He was treated with 9 Gy in
      three fractions weekly of radiotherapy (RT). Clinical response was good and he is
      well and free from progression 4 years and 7 months after RT. A review of the
      literature on the role of RT in the management of hemangiomas is presented.

PMID- 16453299
TI  - Mortality experiences among 15+ year survivors of childhood and adolescent
      cancers.
AB  - BACKGROUND: Studies of childhood and adolescent cancer survivorship have tended
      to focus on limited survival intervals (e.g., 5 and 10 years). Our report
      evaluates gender-specific overall mortality, as well as mortality by age group,
      and by cause, among 15+ year survivors of cancer diagnosed during childhood or
      adolescence. PROCEDURE: This was a retrospective cohort study of 565 15+ year
      childhood cancer survivors from Roswell Park Cancer Institute's Long-Term Follow
      Up Project. Sex- and age-specific person-years at risk were accumulated and
      applied to age-specific mortality rates for New York State, excluding New York
      City. Standardized mortality ratios (SMRs), and 95% confidence intervals, were
      calculated and compared to mortality risks of the general population. RESULTS:
      Second malignancy was the leading cause of death among male and female survivors
      (15/38 deaths, 39%). Excess overall mortality was noted among both males (SMR =
      284) and females (SMR = 371). Significant mortality excesses were seen in both
      genders for deaths due to primary malignant neoplasms and secondary malignancies,
      as well as cardiac deaths among males. Excess mortality was noted across most age
      strata. In the scenario of no cancer relapse, overall mortality in both genders
      did not differ significantly from the general population. CONCLUSIONS: Long-term
      survivors of childhood and adolescent cancers continue to demonstrate significant
      excess mortality. However, overall mortality among 15+ year survivors without a
      relapse appears to be comparable to the general population. The leading cause of
      death among 15+ year survivors is second malignancy in this study, which
      represents a novel and important finding in terms of long-term follow-up.

PMID- 16453302
TI  - Interleukin-1 beta induction of matrix metalloproteinase-1 transcription in
      chondrocytes requires ERK-dependent activation of CCAAT enhancer-binding protein
      beta.
AB  - Interleukin-1 beta (IL-1beta) is a central mediator of inflammation and
      connective tissue destruction in rheumatoid arthritis. IL-1beta activates
      articular chondrocytes to produce matrix metalloproteinase-1 (MMP-1), an enzyme
      capable of dismantling the collagen scaffold of articular cartilage. To define
      the transcription factors and signaling intermediates that activate MMP-1
      transcription in chondrocytes, we performed transient transfection of MMP-1
      promoter constructs followed by reporter assays. These studies identified an IL
      1beta-responsive region of the human MMP-1 promoter that contains a consensus
      CCAAT enhancer-binding protein (C/EBP) binding site. Deletion of this site
      reduced overall transcriptional activity of the MMP-1 promoter, as well as
      decreased fold induction by IL-1beta. IL-1beta stimulation of chondrocytes
      increased binding of C/EBP-beta to the MMP-1 C/EBP site. Extracellular signal
      regulated kinase (ERK) pathway-dependent phosphorylation of C/EBP-beta on
      threonine 235 activates this transcription factor. Here we show that IL-1beta
      stimulation of chondrocytes induced phosphorylation of C/EBP-beta on threonine
      235, and that the ERK pathway inhibitor PD98059 reduced this phosphorylation. We
      further show that PD98059 reduces IL-1beta-induced MMP-1 mRNA expression in
      chondrocytes. Moreover, inhibition of the ERK pathway by expression of dominant
      negative forms of ERK1 and ERK2 impaired the ability of IL-1beta to transactivate
      the MMP-1 promoter. Our findings demonstrate a novel role for C/EBP-beta in IL
      1beta-induced connective tissue disease and define a new nuclear target for the
      ERK pathway in MMP-1 gene activation.

PMID- 16453301
TI  - Extracellular matrix deposition by fibroblasts is necessary to promote capillary
      like tube formation in vitro.
AB  - The contribution of the cellular and fibrillar microenvironment to angiogenesis
      still remains unclear. Our purpose was to evaluate the effect of the
      extracellular matrix deposited by fibroblasts on the capacity of human
      endothelial cells to form capillaries in vitro. We have drastically decreased the
      amount of extracellular matrix surrounding fibroblasts in our model of
      endothelialized-reconstructed connective tissue (ERCT) by culturing it without
      ascorbate. Under these conditions, the number of capillary-like tubes (CLT)
      formed by endothelial cells was reduced by up to 10-fold after 31 days of culture
      compared to controls. This decrease was due neither to a variation of MMP-2 and
      MMP-9 secretion, nor to a reduction in the number of fibroblasts and/or
      endothelial cells, or a diminution of fibroblast growth factor 2 (FGF2)
      synthesis. The secretion of vascular endothelial growth factor (VEGF) by
      fibroblasts accounted for 25-70% of the capillary-like tube formation when
      tissues were cultured in the presence or absence of ascorbate, as demonstrated by
      VEGF-blocking studies. The culture of endothelial cells on a similar
      extracellular matrix but in the absence of living fibroblasts did not promote the
      formation of CLT, even when tissues were fed with fibroblast-conditioned medium.
      Thus, the deposition of a rich extracellular matrix by living fibroblasts
      appeared necessary, but not sufficient to promote capillary-like formation.
      Fibroblasts seem to induce endothelial cells to spontaneously form CLT by
      secreting and organizing an abundant extracellular matrix, which creates a
      microenvironment around cells that could in turn trap growth factors produced by
      fibroblasts and promote three-dimensional cell organization.

PMID- 16453304
TI  - Src oncogene activates MMP-2 expression via the ERK/Sp1 pathway.
AB  - Previous studies demonstrated that activation of Src oncogene increased matrix
      metalloproteinase-2 (MMP-2) expression in various types of cells. In this study,
      we elucidated the underlying mechanism of Src-induced MMP-2. We first used murine
      fibroblast cell line C3H10T1/2 and its v-Src transfectant IV5 to address this
      issue. RT-PCR and promoter activity assay indicated that Src stimulated MMP-2 via
      transcriptional activation. Transfection of constitutively active Src into
      C3H10T1/2 cells also stimulated MMP-2 mRNA expression. Deletion and mutation
      analysis indicated that the Sp1 site located within the -91/-84 region of human
      MMP-2 promoter is the major responsive element for Src. Electrophoresis mobility
      shift assays showed that Src enhanced the binding of Sp1 to this consensus site
      to stimulate MMP-2 gene expression. We next investigated the signaling pathway
      that mediated the effect of Src on MMP-2. Our data showed that extracellular
      signal-regulated kinase (ERK) pathway inhibitor PD98059, but not the c-Jun N
      terminal kinase (JNK) inhibitor SP600125, p38 kinase inhibitor SB203580, and PI3K
      inhibitor wortmannin, attenuated Src-induced MMP-2 promoter activity. These
      inhibitors did not show significant effect on basal MMP-2 promoter activity in
      C3H10T1/2 cells. In addition, the dominant negative mutant of ERK-2 suppressed
      the activation of MMP-2 by Src. Treatment of PD98059 or an Src specific inhibitor
      PP1 reduced Sp1 DNA binding activity in IV5 cells. Taken together, our results
      strongly suggest that Src induces MMP-2 expression via transcription activation
      and the ERK/Sp1 signaling pathway is involved in this process.

PMID- 16453303
TI  - Recombinant human uteroglobin/CC10 inhibits the adhesion and migration of primary
      human endothelial cells via specific and saturable binding to fibronectin.
AB  - Uteroglobin (UG) or Clara Cell 10 kDa protein (CC10) is a small, stable,
      epithelial secretory anti-inflammatory protein. Uteroglobin has been shown to
      inhibit neointimal formation in vivo after balloon angioplasty through an unknown
      mechanism. An interaction between UG and plasma fibronectin (Fn) has been
      demonstrated in mice. Since Fn plays a key role in endothelial cell (EC)
      migration and angiogenesis, we investigated whether recombinant human UG (rhUG)
      affects EC migration via Fn binding. In this report, we show a saturable binding
      of rhUG to Fn depending on Fn conformation and that rhUG is covalently cross
      linked to Fn by transglutaminase (TGase). Additionally, our study highlights that
      rhUG can also bind to exogenously added or self-secreted Fn on the membrane of
      human primary microvascular endothelial cells (HMVEC), although these complexes
      are weakly associated with the plasmalemma. Upon the interaction with Fn in solid
      phase, rhUG strongly inhibits HMVEC attachment on Fn, but not on other ECM
      proteins. Consequently, rhUG also inhibits cell migration in a dose dependent
      fashion (I.C.50 = 65 nM) and hinders the "wound healing" in vitro. The small
      size, stability and human tolerability of rhUG suggest that rhUG in slow-release
      form or genetically delivered could be used in humans to modulate cell/Fn
      interactions in the context of tumor microenvironment or in the context of
      inflammation and fibrosis.

PMID- 16453305
TI  - Solvent polarity effect on excited-state lifetime of carotenoids and some dyes.
AB  - The theory demonstrating the role of medium at the fluorescence quenching of
      polar compounds in solutions is briefly presented. It has been shown, that the
      rate of S(1) --> X(n) nonradiative conversion between the intramolecular charge
      transfer states depends on the permanent dipole moments in the ground (S(0)) and
      excited (S(1), X(n)) states as well as on solvent polarity. A relation for the
      rate of nonradiative excited-state energy conversion has been obtained and
      employed to test the known literature data for solvent effect on the S(1)-state
      lifetime of some biologically significant carotenoids and dyes (phthalimides).
      For phthalimides, the solvent isotope effect on the S(1)-state energy conversion,
      when hydrogen is replaced by deuterium in the OH groups of alcohols and water,
      has been analyzed. Based on the data for fluorescence quenching in solvents of
      different polarity, the dipole moments in the intermolecular charge transfer S(1)
      state have been obtained for carotenoids (peridinin, fucoxanthin, uriolide
      acetate) and for hydrogen-bonding complexes, which are formed by 4-amino-, 4
      methylamino-, and 4-dimethylamino-N-methylphthalimides in alcohols and water.

PMID- 16453307
TI  - Normal mode analysis of the horseradish peroxidase collective motions:
      correlation with spectroscopically observed heme distortions.
AB  - Horseradish peroxidase C is a class III peroxidase whose structure is stabilized
      by the presence of two endogenous calcium atoms. Calcium removal has been shown
      to decrease the enzymatic activity of the enzyme and significantly affect the
      spectroscopically detectable properties of the heme, such as the spin state of
      the iron, heme normal modes, and distortions from planarity. In this work, we
      report on normal mode analysis (NMA) performed on models subjected to 2 ns of
      molecular dynamics simulations to describe the effect of calcium removal on
      protein collective motions and to investigate the correlation between active site
      (heme) and protein matrix fluctuations. We show that in the native peroxidase
      model, heme fluctuations are correlated to matrix fluctuations while they are not
      in the calcium-depleted model.

PMID- 16453306
TI  - Surface-enhanced resonance Raman scattering of porphyrins on gold nanoparticles
      attached to silanized glass plates.
AB  - Surface-enhanced resonance Raman scattering (SERRS) spectra of cationic
      5,10,15,20-tetrakis(1-methyl-4-pyridyl) porphyrin (TMPyP) and anionic 5,10,15,20
      tetrakis(4-sulfonatophenyl) porphyrin (TSPP) were measured from gold surfaces
      prepared by attaching citrate-reduced colloidal nanoparticles to glass slides
      silanized by 3-aminopropyltrimethoxysilane. SERRS spectra of both porphyrins
      obtained in a large concentration range (1 x 10(-4) to 1 x 10(-7)M) of primary
      solution do not show any sign of porphyrin metalation or perturbation of its
      native structure. Optimal adsorption time (15-20 min) and covering concentration
      limit (lower than 1 x 10(-5)M) of porphyrins have been estimated from the
      concentration and soaking time dependences of SERRS spectra.

PMID- 16453308
TI  - Formation of stable nanoparticles via electrostatic complexation between sodium
      caseinate and gum arabic.
AB  - The formation of electrostatic complexes between sodium caseinate and gum arabic
      (GA) was studied as a function of pH (2.0-7.0), using slow acidification in situ
      with glucono-delta-lactone (GDL) or titration with HCl. The colloidal behavior of
      the complexes under specific conditions was investigated using absorbance
      measurements (at 515 or 810 nm) and dynamic light scattering (DLS). In contrast
      to the sudden increase in absorbance and subsequent precipitation of sodium
      caseinate solutions at pH < 5.4, the absorbance values of mixtures of sodium
      caseinate and GA increased to a level that was dependent on GA concentration at
      pH 5.4 (pH(c)). The absorbance values remained constant with further decreases in
      pH until a sudden increase in absorbance was observed (at pH(phi)). The pH(phi)
      was also dependent upon the GA concentration. Dynamic light scattering (DLS) data
      showed that the sizes of the particles formed by the complexation of sodium
      caseinate and GA between pH(c) and pH(phi) were between 100 and 150 nm and these
      nanoparticles were visualized using negative staining transmission electron
      microscopy (TEM). Below pH(phi), the nanoparticles associated to form larger
      particles, causing phase separation. zeta-Potential measurements of the
      nanoparticles and chemical analysis after phase separation showed that phase
      separation was a consequence of charge neutralization. The formation of complexes
      between sodium caseinate and GA was inhibited at high ionic strength (>50 mM
      NaCl). It is postulated that the structure of the nanoparticles comprises an
      aggregated caseinate core, protected from further aggregation by steric repulsion
      of one, or more, electrostatically attached GA molecules.

PMID- 16453309
TI  - Structure and pH sensitivity of the transmembrane segment 3 of rhodopsin.
AB  - Activation of G protein-coupled receptors (GPCRs) originates in ligand-induced
      protein conformational changes that are transmitted to the cytosolic receptor
      surface. In the photoreceptor rhodopsin, and possibly other rhodopsin-like GPCRs,
      protonation of a carboxylic acid in the conserved E(D)RY motif at the cytosolic
      end of transmembrane helix 3 (TM3) is coupled to receptor activation. Here, we
      have investigated the structure of synthetic peptides derived from rhodopsin TM3.
      Polarized FTIR spectroscopy reveals a helical structure of a 31-mer TM3 peptide
      reconstituted into PC vesicles with a large tilt of 40-50 degrees of the helical
      axis relative to the membrane normal. Helical structure is also observed for the
      TM3 peptide in detergent micelles and depends on pH, especially in the C-terminal
      sequence. In addition, the fluorescence emission of the single tyrosine of the
      D(E)RY motif in the TM3 peptide exhibits a pronounced pH sensitivity that is
      abolished when Glu is replaced by Gln, demonstrating that protonation of the
      conserved Glu side chain affects the structure in the environment of the D(E)RY
      motif of TM3. The pH regulation of the C-terminal TM3 structure may be an
      intrinsic feature of the E(D)RY motif in other class I receptors, allowing the
      coupling of protonation and conformation of membrane-exposed residues in full
      length GPCRs.

PMID- 16453310
TI  - Neural activity related to self- versus externally generated painful stimuli
      reveals distinct differences in the lateral pain system in a parametric fMRI
      study.
AB  - Self-generated sensory stimulation can be distinguished from externally generated
      stimulation that is otherwise identical. To determine how the brain
      differentiates external from self-generated noxious stimulation and which
      structures of the lateral pain system use neural signals to predict the sensory
      consequences of self-generated painful stimulation, we used functional magnetic
      resonance imaging to examine healthy human subjects who received thermal-contact
      stimuli with noxious and non-noxious temperatures on the resting right hand in
      random order. These stimuli were internally (self-generated) or externally
      generated. Two additional conditions served as control conditions: to account for
      stimulus onset uncertainty, acoustic stimuli preceding the same thermal stimuli
      were used with variable or fixed delays but without any stimulus-eliciting
      movements. Whereas graded pain-related activity in the insula and secondary
      somatosensory cortex (SII) was independent of how the stimulus was generated, it
      was attenuated in the primary somatosensory cortex (SI) during self-generated
      stimulation. These data agree with recent concepts of the parallel processing of
      nociceptive signals to the primary and secondary somatosensory cortices. They
      also suggest that brain areas that encode pain intensity do not distinguish
      between internally or externally applied noxious stimuli, i.e., this adaptive
      biological mechanism prevents harm to the individual. The attenuated activation
      of SI during self-generated painful stimulation might be a result of the
      predictability of the sensory consequences of the pain-related action.

PMID- 16453311
TI  - Chronic morphine treatment alters expression of N-methyl-D-aspartate receptor
      subunits in the extended amygdala.
AB  - The nucleus accumbens (NAcc) and central amygdala (CeA) are parts of the extended
      amygdala, a complex that plays a key role in drug abuse and dependence. Our
      previous studies showed that opiates and ethanol alter glutamatergic transmission
      in these regions. N-methyl-D-aspartate (NMDA) receptors are key components of
      glutamatergic transmission likely involved in the development of opiate tolerance
      and dependence. In this study we examined the effects of chronic morphine
      administration on gene and protein expression of three major NMDA receptors
      subunits (NR1, NR2A, and NR2B) in NAcc and CeA. Real-time PCR showed no
      differences in mRNA levels of any of the subunits in the whole NAcc between naive
      and morphine-dependent rats. However, at the protein level, immunoblotting
      revealed that chronic morphine significantly increased levels of NR1 and NR2B
      subunits. In contrast to the case for NAcc, in CeA we found an increased mRNA
      level for the NR1 subunit only but unchanged protein levels of all three subunits
      in morphine-dependent rats. The altered expressions of NMDA receptor subunits,
      especially in NAcc, of morphine-dependent rats may represent a neuroadaptation to
      chronic morphine and suggest a mechanism for the changes of glutamatergic
      transmission found in the extended amygdala in dependent rats. In addition, our
      results indicate a region-specific response of NMDA receptor subunits to chronic
      morphine administration at the gene and protein levels.

PMID- 16453312
TI  - Inhibition of nociceptive responses of spinal cord neurones during hypertension
      involves the spinal GABAergic system and a pain modulatory center located at the
      caudal ventrolateral medulla.
AB  - The mechanisms of hypertension-induced hypoalgesia were studied in a model of
      hypertension induced by adenosine receptors blockade with the non-selective
      antagonist 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) during 7 days. Based on the
      positive correlation between pain thresholds and noxious-evoked expression of the
      c-fos protooncogene in spinal cord neurones, we used this marker of nociceptive
      activation of spinal neurones to evaluate the involvement of the spinal GABAergic
      system and the caudal ventrolateral medulla (VLM), an important inhibitory
      component of the supraspinal endogenous pain modulatory system. In DPSPX-treated
      animals, a 20% increase in blood pressure was achieved along with a decrease in
      Fos expression in the superficial (laminae I-II) and deep (laminae III-VII)
      dorsal horn. In these animals, lower percentages of neurones labeled for GABAB
      receptors that expressed Fos were obtained in the superficial dorsal horn.
      Lesioning the VLMlat with quinolinic acid prevented the decrease in Fos
      expression at the spinal cord of DPSPX-hypertensive rats whereas in normotensive
      animals, no changes in Fos expression were detected. The present results support
      previous findings that hypertension is associated with a decrease of nociceptive
      activation of spinal cord neurones, through descending inhibition exerted by the
      VLMlat. This study further shows that during hypertension a decrease in the
      expression of GABAB receptors in nociceptive spinal neurones occurs, probably due
      to changes in the local GABAergic inhibitory system.

PMID- 16453313
TI  - Blood donations, iron stores, and risk of Parkinson's disease.
AB  - Iron overload and systemic iron stores may be important in the pathogenesis of
      Parkinson's disease (PD). We therefore examined the association between blood
      donations, which reduce body iron stores, and risk of PD in the Health
      Professionals Follow-Up Study, a large cohort investigation of U.S. men. Our
      hypothesis was that blood donation reduces the risk of PD by lowering systemic
      iron stores. Although the number of blood donations was inversely related to the
      ferritin levels in a subsample of the study population, no association was found
      between the number of blood donations and risk of PD (P for trend = 0.6).
      Unexpectedly, the risk of PD was higher among men who reported recent multiple
      blood donations (P for trend = 0.05). The results of this study do not support
      the hypothesis that reduced systemic iron stores lower the risk of PD.

PMID- 16453314
TI  - Automatic selection of arterial input function using cluster analysis.
AB  - Quantification of cerebral blood flow (CBF) using dynamic susceptibility contrast
      MRI requires determination of the arterial input function (AIF) representing the
      delivery of intravascular tracer to tissue. This is typically accomplished
      manually by inspection of concentration time curves (CTCs) in regions containing
      the ICA, VA, and MCA. This is, however, a time consuming and operator dependent
      procedure. We suggest a completely automatic procedure for establishing the AIF
      based on a cluster analysis algorithm. In 20 normal subjects CBF maps calculated
      in 2 slices by the automatic procedure were compared to maps obtained with AIFs
      selected individually by 7 experienced operators. The average manual to automatic
      CBF ratio was 1.03+/-0.15 in the lower slice and 1.05+/-0.12 in the upper slice,
      demonstrating excellent agreement between the manual and automatic method. The
      algorithm provides means for objectively assessing AIF candidates in local AIF
      search algorithms designed to reduce bias due to delay and dispersion. Given the
      reproducibility and speed (10 s) of the automatic method, we speculate that it
      will greatly improve the accuracy of perfusion images and facilitate their use in
      clinical diagnosis and decision-making, particularly in acute stroke but also in
      cerebrovascular disease in general.

PMID- 16453315
TI  - Mice with a deletion in the first intron of the Col1a1 gene develop dissection
      and rupture of aorta in the absence of aneurysms: high-resolution magnetic
      resonance imaging, at 4.7 T, of the aorta and cerebral arteries.
AB  - Deletion of the majority of the first intron of the Col1a1 gene in mice leads to
      decreased type I collagen synthesis and content in the aortic wall. In 54% of
      cases, mice homozygous for the Col1a1 mutation die of thoracic hemorrhage by the
      age of 18 months. It is unknown whether the fatal bleeding results from an acute
      dissection of the aortic wall or a gradually developing dilatation of the medial
      layer prior to rupture. We optimized high-resolution MRI methods using a 4.7 T MR
      scanner to obtain in vivo images of the entire mouse aorta. The MR images were
      acquired in three imaging planes using gradient echo, spin echo, and spin echo
      with inversion recovery pulse sequences with a maximum in-plane resolution of 68
      x 68 microm and acquisition times less than 10 min. In five Col1a1 mutated mice
      aged 16 months, the MR images showed no signs of aneurysmal dilatation, wall
      defects, or former dissection, suggesting that the mechanism for aortic rupture
      is an acute dissection of the aortic medial layer. Cerebral arteries were imaged
      using a three-dimensional time of fight pulse sequence. The resolution of 73 x 73
      x 94 microm showed normal cerebral arteries. Histology showed a 22% thinner
      cerebral artery wall in Col1a1 mutated mice.

PMID- 16453317
TI  - Rapamycin causes regression of astrocytomas in tuberous sclerosis complex.
AB  - OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder characterized
      by the formation of hamartomas in multiple organs. Five to 15% of affected
      individuals display subependymal giant cell astrocytomas, which can lead to
      substantial neurological and postoperative morbidity due to the production of
      hydrocephalus, mass effect, and their typical location adjacent to the foramen of
      Monro. We sought to see whether therapy with oral rapamycin could affect growth
      or induce regression in astrocytomas associated with TSC. METHODS: Five subjects
      with clinically definite TSC and either subependymal giant cell astrocytomas (n =
      4) or a pilocytic astrocytoma (n = 1) were treated with oral rapamycin at
      standard immunosuppressive doses (serum levels 5-15 ng/ml) from 2.5 to 20 months.
      All lesions demonstrated growth on serial neuroimaging studies. Magnetic
      resonance imaging scans were performed before and at regular intervals following
      initiation of therapy. RESULTS: All lesions exhibited regression and, in one
      case, necrosis. Interruption of therapy resulted in regrowth of subependymal
      giant cell astrocytomas in one patient. Resumption of therapy resulted in further
      regression. Treatment was well tolerated. INTERPRETATION: Oral rapamycin therapy
      can induce regression of astrocytomas associated with TSC and may offer an
      alternative to operative therapy of these lesions.

PMID- 16453316
TI  - 1,026 experimental treatments in acute stroke.
AB  - OBJECTIVE: Preclinical evaluation of neuroprotectants fostered high expectations
      of clinical efficacy. When not matched, the question arises whether experiments
      are poor indicators of clinical outcome or whether the best drugs were not taken
      forward to clinical trial. Therefore, we endeavored to contrast experimental
      efficacy and scope of testing of drugs used clinically and those tested only
      experimentally. METHODS: We identified neuroprotectants and reports of
      experimental efficacy via a systematic search. Controlled in vivo and in vitro
      experiments using functional or histological end points were selected for
      analysis. Relationships between outcome, drug mechanism, scope of testing, and
      clinical trial status were assessed statistically. RESULTS: There was no evidence
      that drugs used clinically (114 drugs) were more effective experimentally than
      those tested only in animal models (912 drugs), for example, improvement in focal
      models averaged 31.3 +/- 16.7% versus 24.4 +/- 32.9%, p > 0.05, respectively.
      Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR)
      criteria was highly variable, and no relationship was found between mechanism and
      efficacy. INTERPRETATION: The results question whether the most efficacious drugs
      are being selected for stroke clinical trials. This may partially explain the
      slow progress in developing treatments. Greater rigor in the conduct, reporting,
      and analysis of animal data will improve the transition of scientific advances
      from bench to bedside.

PMID- 16453318
TI  - In vivo detection of brain glycine with echo-time-averaged (1)H magnetic
      resonance spectroscopy at 4.0 T.
AB  - A single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) method is
      described that enables the in vivo measurement of endogenous brain glycine (Gly)
      levels in human subjects. At 4.0 T, TE-averaging (1)H-MRS dramatically attenuates
      the overlapping myo-inositol (mI) resonances at 3.52 ppm, permitting a more
      reliable measure of the Gly singlet peak. This methodology initially is described
      and tested in phantoms. The phantom data infers that the 3.55-ppm peak
      predominantly is Gly with a smaller contribution from mI. The composite resonance
      thus is differentiated from pure Gly and mI and is labeled Gly*. The mI
      contribution was calculated as <2% of the total Gly* signal for a 1:1 mI/Gly
      mixture. The technique subsequently was used to acquire TE-averaged (1)H-MRS data
      from the occipital cortex of healthy control subjects. The resultant spectra
      closely resembled experimental phantom data. LC-model analysis provided a means
      for quantifying TE-averaged (1)H-MRS spectra and a mean test-retest variability
      measure of 15% was established for brain Gly* levels in studies of six healthy
      subjects.

PMID- 16453319
TI  - Analysis of residual coronary artery motion for breath hold and navigator
      approaches using real-time coronary MRI.
AB  - Coronary artery MRI methods utilize breath holds, or diaphragmatic navigators, to
      compensate for respiratory motion. To increase image quality and navigator (NAV)
      gating efficiency, slice tracking is used, with more sophisticated affine motion
      models recently introduced. This study assesses the extent of remaining coronary
      artery motion in free breathing NAV and single and multi breath hold coronary
      artery MRI. Additionally, the effect of the NAV gating window size was examined.
      To visualize and measure the respiratory induced motion, an image containing a
      coronary artery cross section was acquired at each heartbeat. The amount of
      residual coronary artery displacement was used as a direct measure for the
      performance of the respiratory motion correction method. Free breathing studies
      with motion compensation (slice tracking with 5 mm gating window) had a similar
      amount of residual motion (0.76+/-0.17 mm) as a single breath hold (0.52+/-0.20
      mm) and were superior to multiple breath holds (1.22+/-0.60 mm). Affine NAV
      methods allowed for larger gating windows ( approximately 10 mm windows) with
      similar residual motion (0.74+/-0.17 mm). In this healthy adult cohort (N=10),
      free-breathing NAV methods offered respiratory motion suppression similar to a
      single breath hold.

PMID- 16453320
TI  - Fine-needle aspiration biopsy of Hurthle cell lesions of the thyroid gland: A
      cytomorphologic study of 139 cases with statistical analysis.
AB  - BACKGROUND: Lesions of the thyroid gland composed of Hurthle cells encompass
      pathologic entities ranging from hyperplastic nodules with Hurthle cell
      metaplasia to Hurthle cell carcinomas. The cytologic distinction between these
      entities can be diagnostically challenging. Many cytologic features of Hurthle
      cell lesions that distinguish neoplastic Hurthle cell lesions requiring surgery
      from those that are benign and nonneoplastic have been described, but with
      variable usefulness. This is due, in part, to the small numbers of cases examined
      in previous studies and the limited application of statistical analysis. A
      morphologic study was made of 139 Hurthle cell lesions of the thyroid gland and
      statistical analysis applied to identify a set of cytomorphologic features that
      distinguish benign Hurthle cell lesions (BHCL) from Hurthle cell neoplasms (HCN).
      METHODS: Fine-needle aspiration biopsies (FNABs) of thyroid nodules with a
      predominant Hurthle cell component and corresponding histologic followup were
      included in the study. Cases were divided into BHCL and HCN groups on the basis
      of the histologic diagnosis. All cases were reviewed to assess the following 14
      cytologic features: overall cellularity, cytoarchitecture, percentage of Hurthle
      cells, percentage of single cells, percentage of follicular cells observed as
      naked Hurthle cell nuclei, background colloid, chronic inflammation, cystic
      change, transgressing blood vessels (TBV), intracytoplasmic lumina, presence of
      multinucleated Hurthle cells, nuclear to cytoplasmic ratio, nuclear
      pleomorphism/atypia, and nucleolar prominence. The results were evaluated by
      using univariate and stepwise logistic regression (SLR) analysis; statistical
      significance was achieved at P-values < 0.05. RESULTS: One hundred thirty-nine
      FNAB specimens, corresponding to 56 HCN and 83 BHCL, fulfilled the study
      criteria. Six of the 14 cytologic features evaluated were shown by univariate
      analysis to be statistically significant in predicting HCN: nonmacrofollicular
      architecture (P < 0.001), absence of background colloid (P < 0.001), absence of
      chronic inflammation (P < 0.001), presence of TBV (P < 0.001), > 90% Hurthle
      cells (P < 0.001), and >10% single Hurthle cells (P = 0.014). The first four of
      these features were also shown to be statistically significant in the SLR
      analysis (P = 0.005, 0.010, 0.016, and 0.045, respectively), and when all four of
      these features were present HCN was correctly identified 86% of the time.
      CONCLUSIONS: In the current study of 139 FNAB specimens of thyroid Hurthle cell
      nodules, 14 cytologic features were examined and 6 were found to be statistically
      significant in identifying HCN. The following four features, when found in
      combination, were found to be highly predictive of HCN: nonmacrofollicular
      architecture, absence of colloid, absence of inflammation, and presence of TBV.

PMID- 16453321
TI  - Submental Nd:Yag laser-assisted liposuction.
AB  - BACKGROUND: Liposuction of the neck is currently one of the most common cosmetic
      surgical procedures. In the present study, the author describes his experience
      with neck and jowl laser-assisted liposuction. STUDY DESIGN/MATERIALS AND
      METHODS: In this procedure, submental lipodystrophy is treated with an Nd:YAG
      laser, at a 1,064 nm wavelength. Over a 5-year-period, 82 subjects were treated
      using 6-W power, 40-Hz frequency, 150-mJ energy, and 100-microsecond pulse width
      parameters. Histology was performed on fatty tissue samples. RESULTS: Submental
      laser-assisted liposuction resulted in significant cosmetic improvement.
      Histology revealed a rupture of the adipocyte membrane as well as collagen
      coagulation and channels along the fatty tissue. Additionally, small blood
      vessels were coagulated. An adequate skin contraction was observed with an
      improvement of the cervicofacial region. CONCLUSIONS: The Nd:YAG laser is a
      useful tool for the treatment of local lipodistrophy. The laser proved to be
      effective for cellular lysis and collagen neoformation.

PMID- 16453322
TI  - AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders.
AB  - OBJECTIVE: Joubert syndrome (JS) is a recessively inherited developmental brain
      disorder with several identified causative chromosomal loci. It is characterized
      by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain "molar
      tooth" sign, a finding shared by a group of Joubert syndrome-related disorders
      (JSRDs), with wide phenotypic variability. The frequency of mutations in the
      first positionally cloned gene, AHI1, is unknown. METHODS: We searched for
      mutations in the AHI1 gene among a cohort of 137 families with JSRD and
      radiographically proven molar tooth sign. RESULTS: We identified 15 deleterious
      mutations in 10 families with pure JS or JS plus retinal and/or additional
      central nervous system abnormalities. Mutations among families with JSRD
      including kidney or liver involvement were not detected. Transheterozygous
      mutations were identified in the majority of those without history of
      consanguinity. Most mutations were truncating or splicing errors, with only one
      missense mutation in the highly conserved WD40 repeat domain that led to disease
      of similar severity. INTERPRETATION: AHI1 mutations are a frequent cause of
      disease in patients with specific forms of JSRD.

PMID- 16453323
TI  - Auto-calibrated parallel spiral imaging.
AB  - This work describes an auto-calibrated method for parallel imaging with spiral
      trajectory. The method is a k-space approach where an interpolation kernel,
      accounting for coil sensitivity factors, is derived from experimental data and
      used to interpolate the reduced data set in parallel imaging to estimate the
      missing k-space data. For the case of spiral imaging, this interpolation kernel
      is defined along radial directions so that missing spiral interleaves can be
      estimated directly from neighboring interleaves. This kernel is invariant along
      the radial direction but varies azimuthally. Therefore, the k-space is divided
      into angular sectors and sector-specific kernels are used. It is demonstrated
      experimentally that relatively few sectors are sufficient for accurate
      reconstruction, allowing for efficient implementation. The interpolation kernels
      can be derived either from a separate calibration scan or self-calibration data
      available with a dual-density spiral acquisition. The reconstruction method is
      implemented with two sampling strategies and experimentally demonstrated to be
      robust.

PMID- 16453324
TI  - Cholinergic neuromuscular hyperactivity in patients with myasthenia gravis
      seropositive for MuSK antibody.
AB  - A 75-year-old man with severe oculobulbar myasthenia gravis (MG) treated with
      acetylcholine esterase inhibitors (AChEIs) was found to have muscle-specific
      tyrosine kinase (MuSK) antibodies. Neurophysiological examination displayed extra
      repetitive discharges after the compound motor action potential (CMAP) at low
      frequency stimulation, possibly triggered by AChEI. This indicates an abnormal
      sensitivity to acetylcholine in patients with MuSK antibodies and may be a useful
      indicator of the adverse effect of AChEI treatment in these patients.

PMID- 16453325
TI  - Axonal function and activity-dependent excitability changes in myotonic
      dystrophy.
AB  - To investigate peripheral nerve function and its potential contribution to
      symptoms of weakness in myotonic dystrophy type 1 (MD), nerve excitability was
      assessed in 12 MD patients. Compound muscle action potentials (CMAPs) were
      recorded at rest from abductor pollicis brevis (APB) following stimulation of the
      median nerve. Stimulus-response behavior, threshold electrotonus, a current
      threshold relationship, and recovery cycles were successfully recorded in each
      patient. Compared with controls, there was significant reduction in CMAP
      amplitude in MD patients. This was accompanied by reduction in depolarizing
      threshold electrotonus and an increase in refractoriness and in the duration of
      the relative refractory period. To determine whether alteration in axonal resting
      membrane potential was a factor underlying these changes, axonal excitability was
      assessed following maximal contraction of APB for 60 seconds. Following
      contraction, there was reduction in CMAP amplitude for a submaximal stimulus (by
      51.5+/-11.8%) and an increase in super-excitability (of 22.2+/-12.0%), consistent
      with activity-dependent hyperpolarization, with a greater increase in threshold
      for MD patients compared to controls (MD group, 22.3+/-5.1%; controls, 11.7+/
      2.1%; P<0.04) and prolonged recovery to baseline. The present study has
      established that greater activity-dependent changes in excitability may be
      induced in MD patients by maximal voluntary contraction when compared to
      controls. The excitability changes and prolonged recovery of threshold following
      contraction are likely to contribute to symptoms of fatigue and weakness in MD
      patients.

PMID- 16453326
TI  - Lewis-Sumner syndrome in hepatitis C virus infection: a possible pathogenetic
      association with therapeutic problems.
AB  - A patient with chronic hepatitis from hepatitis C virus (HCV) infection developed
      Lewis-Sumner syndrome (LSS). The neuropathy worsened after intravenous
      immunoglobulins, remitted after intravenous methylprednisolone, relapsed during
      interferon-alpha, but responded again to steroids continued for 68 weeks with
      clinical remission and without worsening of hepatitis. We are not aware of other
      reports of HCV infection and LSS. This association may be coincidental or related
      to a virus-triggered immune-mediated process. Although the coexistence of a
      dysimmune neuropathy with hepatitis makes problematic the choice of treatment, we
      emphasize that the patient's condition during treatment with steroids and the 46
      following weeks without therapy has been excellent.

PMID- 16453327
TI  - Neuromyelitis optica IgG predicts relapse after longitudinally extensive
      transverse myelitis.
AB  - OBJECTIVE: We investigated whether neuromyelitis optica (NMO) IgG seropositivity
      at the initial presentation of longitudinally extensive transverse myelitis
      (LETM) predicts relapse of myelitis or development of optic neuritis. METHODS:
      Prospective study of patients with initial LETM who were tested for the presence
      of NMO-IgG. RESULTS: Eleven of 29 patients (37.9%) were seropositive after a
      first attack of LETM spanning three or more vertebral segments on magnetic
      resonance imaging. Of 23 patients followed up for 1 year, none of 14 who were
      seronegative experienced a relapse or developed optic neuritis. Of 9 seropositive
      patients, 5 developed a second event: 4 of 9 (44%) developed recurrent transverse
      myelitis and 1 of 9 (11%) developed optic neuritis (p = 0.004). INTERPRETATION:
      LETM represents an inaugural or limited form of NMO in a high proportion of
      patients. The 40% of patients who are seropositive for NMO-IgG are at high risk
      for relapse.

PMID- 16453328
TI  - Intranasal interleukin-12 gene therapy enhanced the activity of ifosfamide
      against osteosarcoma lung metastases.
AB  - BACKGROUND: Cyclophosphamide (CTX) and ifosfamide (IFX) are alkylating agents
      used to treat osteosarcoma (OS). It was previously demonstrated that the
      sensitivity of OS cells to 4-hydroperoxycyclophosphamide (4-HC, the active
      metabolite of CTX) is augmented by interleukin (IL)-12 in vitro through a
      mechanism involving the Fas/FasL pathway. The purpose of these studies was to
      determine whether this synergistic effect is operational in vivo. METHODS: Mice
      were injected intravenously with human LM7 osteosarcoma cells. Treatment was
      initiated with IFX (2.5 mg/kg intraperitoneally) with or without intranasal
      polyethylenimine (PEI):IL-12 gene therapy given twice weekly for 6 weeks.
      RESULTS: Expression of IL-12 protein in the lung was demonstrated in all mice
      receiving intranasal PEI:IL-12 but not in control mice or those treated with IFX
      alone. Increased expression of FasL was detected in lungs of all mice receiving
      IFX. Both IFX and PEI:IL-12 alone significantly inhibited lung metastasis when
      compared with control groups (P < 0.05). However, the most significant tumor
      effect was observed in mice receiving IFX+PEI:IL-12 (P < 0.01).
      Immunohistochemical staining for CD31 and basic fibroblast growth factor (bFGF)
      and the number of proliferating cells as quantified by proliferating cell nuclear
      antigen (PCNA) staining were also most significantly decreased in mice receiving
      combination therapy. CONCLUSIONS: These data indicate that combining IFX and IL
      12 may have therapeutic potential and that this increased efficacy may be
      mediated through a mechanism involving the Fas/FasL pathway.

PMID- 16453329
TI  - Quality of survival reporting in chemotherapy and surgery trials in patients with
      metastatic colorectal carcinoma.
AB  - BACKGROUND: Patients with metastatic colorectal carcinoma (MCC) to the liver
      receive conflicting management recommendations because of the lack of prospective
      randomized controlled trials (RCTs) clarifying the optimal management in this
      disease. The objective of the current study was to evaluate the reporting of
      prognostic factors in MCC from chemotherapy and surgery trials and evaluate the
      ability to compare these results across treatments. METHODS: RCTs and
      retrospective series of greater than 75 MCC patients published between 1980-2004
      were reviewed to identify 10 critical prognostic elements of overall survival
      reported in both types of journals. RESULTS: A review 92 RCTs and 116
      retrospective reports with 64,898 patients analyzed found 7 (3%) reporting all
      prognostic factors, with both studies demonstrating no difference in the success
      of reporting criteria met. The only criterion that was universally reported among
      both chemotherapy and surgery trials was the mortality rates of the study. All
      remaining prognostic factors in the evaluation of overall survival were
      significantly different between both chemotherapy and surgical studies.
      Considerable variation was observed in the disease-free interval, number of
      hepatic metastases, size of hepatic metastases, and performance status, and were
      significantly different among some of the most significant factors for patients
      evaluating treatment: complication reporting, surgical margin evaluation, and
      overall response rate. CONCLUSIONS: The reporting of results in MCC in
      chemotherapy trials and surgical reports is limited to general outcomes, with a
      paucity of prognostic factors, which hinders any ability to compare results
      across treatments. A mandatory reporting criteria of all metastatic colorectal
      trials is imperative to optimally manage these patients in both academic and
      community centers.

PMID- 16453331
TI  - Mid-IR laser ablation of articular and fibro-cartilage: a wavelength dependence
      study of thermal injury and crater morphology.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate areas of
      collateral thermal injury and crater morphology for evidence of wavelength
      dependent effects on the ablation of articular cartilage and fibro-cartilage
      (meniscus) using selected mid-IR wavelengths produced by a free electron laser.
      STUDY DESIGN/MATERIALS AND METHODS: Two types of cartilage, articular cartilage
      and fibro-cartilage were used in the study. The wavelengths (lambda) evaluated
      were 2.79, 2.9, 6.1, and 6.45 microm generated by a free electron laser (FEL)
      using a 4 microseconds macropulse configuration. The zone of thermal injury and
      crater morphology produced by laser ablation were examined by light microscopy
      following standard histologic processing. RESULTS: The zone of thermal injury and
      crater morphology created in cartilage by the FEL at selected mid-IR wavelengths
      were examined as a function of incident radiant exposure. Ablation using lambda =
      6.1 microm provided the largest crater size for both articular and fibro
      cartilage at all radiant exposures. For the zones of collateral thermal injury in
      articular cartilage, lambda = 6.1 microm produced the least thermal injury at the
      radiant exposure of 7.6 J/cm2. When the radiant exposure is increased to 20.4
      J/cm2, both lambda = 6.1 and 6.45 microm produced less thermal injury than the
      ablation using lambda = 2.79 and 2.9 microm. The greatest amount of collateral
      thermal injury was produced by lambda = 2.79 microm for both tissue types.
      CONCLUSIONS: The results demonstrate that crater depth and collateral thermal
      injury produced in articular cartilage and fibro-cartilage are wavelength
      dependent with 6.1 microm providing the largest craters at all radiant exposures.
      The least amount of thermal injury was created in articular cartilage using
      lambda = 6.1 microm at the radiant exposure of 7.6 J/cm2. Both 6.1 and 6.45
      microm wavelengths demonstrated similar amount of thermal injury at 20 J/cm2 that
      was less than lambda = 2.79 and 2.9 microm at similar fluences. These
      observations are explained based on the absorption by water and protein in the
      tissue types studied. It is further observed that the use of crater dimensions
      may not provide a reliable estimate for the amount of tissue removal provided by
      an ablation procedure.

PMID- 16453330
TI  - Occult hepatitis B virus infection is associated with the development of
      hepatocellular carcinoma in chronic hepatitis C patients.
AB  - BACKGROUND: Occult hepatitis B virus (HBV) infection frequently occurs in
      patients with HBV surface antigen (HBsAg)-negative chronic liver disease, and
      much evidence suggests that it is a risk factor for hepatocellular carcinoma
      (HCC) development. However, to the authors' knowledge, no follow-up study has
      been performed to date evaluating HCC occurrence over time in chronic hepatitis
      patients with or without occult HBV infection. METHODS: A cohort of the 380 HBsAg
      negative chronic hepatitis patients attending the study institution between 1991
      2000 were evaluated and tested for occult HBV DNA by analysis of liver biopsy
      specimens. RESULTS: There were 135 patients (35.5%) with occult HBV and 245
      patients (64.5%) without occult HBV. Cirrhosis was significantly associated with
      occult HBV infection (P = 0.01). One hundred thirty-four of these patients were
      followed for a minimum of 50 months (median, 82.8 +/- 32.6 mos). Fifty-three
      patients (39%) were occult HBV carriers and 81 (61%) were not. Nine patients
      developed HCC during the follow-up; eight were positive and one was negative for
      occult HBV (P = 0.002). CONCLUSIONS: The current observational cohort study
      showed that, among the HBsAg-negative patients with chronic hepatitis, HCC
      develops for the most part in carriers of occult HBV. Therefore, the evaluation
      of HBV genomes in chronic hepatitis patients appears to be a powerful tool for
      the identification of individuals at higher risk of HCC development.

PMID- 16453332
TI  - Decrease in motor performance in children with cancer is independent of the
      cumulative dose of vincristine.
AB  - BACKGROUND: Impaired performance on motor tasks in children treated for acute
      lymphoblastic leukemia (ALL) after completion of treatment is often attributed to
      vincristine (VCR). Whether motor problems persist in other children who receive
      different cumulative doses of VCR is to the authors' knowledge not known. The
      objective of the current study was to determine the extent of motor problems in
      children with ALL, Wilms tumor (WT), B-cell non-Hodgkin lymphoma (B-NHL), and
      malignant mesenchymal tumors (MMT) and whether these motor problems were related
      to VCR dose. METHODS: In 128 children ages 4-12 years who completed treatment
      after at least 1 year, motor performance was measured using the Movement
      Assessment Battery for Children (m-ABC). RESULTS: The m-ABC scores of the total
      study group were significantly lower than those of the normal population (P <
      0.001). There were no differences in scores noted between children with ALL, WT,
      B-NHL, or MMT. There also were no differences noted between those children with
      ALL who had received pulses of VCR and steroids during maintenance therapy and
      those who had not. All groups demonstrated large variability in scores. Scores
      were not found to be significantly different between those children who had
      received low (< 20 mg/m(2)), intermediate (20-40 mg/m(2)), or high (> 40 mg/m(2))
      cumulative doses of VCR. Cumulative doses of corticosteroids and methotrexate did
      not affect scores, nor did age at diagnosis and time since the completion of
      therapy. CONCLUSIONS: Although motor performance was impaired in all patient
      groups, no correlation was found between motor performance and the cumulative
      dose of VCR or other drugs, age, and follow-up time. Future studies have to
      address several issues, including whether polymorphisms in drug metabolizing
      genes or drug target genes explain the significant variability noted in the long
      term motor outcome of children with cancer.

PMID- 16453333
TI  - Defining "success" in recruitment of underrepresented populations to cancer
      clinical trials: moving toward a more consistent approach.
AB  - Although medically underserved groups bear a heavy burden of cancer disease and
      governmental agencies have required inclusion of minorities and women in cancer
      clinical trials since 1993, many of these groups are underrepresented in cancer
      prevention or treatment clinical trials. To assess and enhance recruitment of
      underrepresented populations into cancer-related clinical trials, investigators
      and governmental agencies need consistent measurement approaches for recruitment
      that can be applied to diverse settings where trials are conducted. We conducted
      a systematic review to evaluate what measurement approaches were used to evaluate
      the success of recruitment of underrepresented groups into cancer prevention or
      treatment trials, and whether these recruitment goals were stated a priori. Only
      two articles reported an a priori recruitment goal. The recruitment measurement
      approaches varied considerably, with no consistent standard, especially for
      individual trials. By using the empiric evidence from this review in conjunction
      with the National Institutes of Health (NIH) guidelines, we constructed a
      framework for choosing consistent a priori recruitment goals for underrepresented
      groups based on the research question and study location. Using consistent
      measurement approaches for underrepresented groups will improve comparability of
      recruitment strategies across trials, improve equity in distribution of benefits
      and burdens of cancer-related clinical trials, and may improve applicability of
      trial results to multiple populations.

PMID- 16453334
TI  - Development of a reinforced porcine elastin composite vascular scaffold.
AB  - Elastin, a principal structural component of native arteries, has distinct
      biological and mechanical advantages when used as a biomaterial; however, its low
      ultimate tensile strength has limited its use as an arterial conduit. We have
      developed a scaffold, consisting of a purified elastin tubular conduit
      strengthened with fibrin bonded layers of acellular small intestinal submucosa
      (aSIS) for potential use as a small diameter vascular graft. The addition of aSIS
      increased the ultimate tensile strength of the elastin conduits nine-fold. Burst
      pressures for the elastin composite vascular scaffold (1,396 +/- 309 mmHg) were
      significantly higher than pure elastin conduits (162 +/- 36 mmHg) and comparable
      to native saphenous veins. The average suture pullout strength of the elastin
      composite vascular scaffolds was 14.612 +/- 3.677 N, significantly higher than
      the pure elastin conduit (0.402 +/- 0.098 N), but comparable to native porcine
      carotid arteries (13.994 +/- 4.344 N). Cyclic circumferential strain testing
      indicated that the composite scaffolds were capable of withstanding physiological
      loading conditions for at least 83 h. Implantation of the elastin composites as
      carotid interposition grafts in swine demonstrated its superiority to clinically
      acceptable ePTFE with significantly longer average patency times of 5.23 h
      compared to 4.15 h. We have developed a biologically based elastin scaffold with
      suitable mechanical properties and low thrombogenicity for in vivo implantation,
      and with the potential for cellular repopulation and host integration
      reestablishing an appropriate elastic artery.

PMID- 16453335
TI  - Visual, auditory, sensory, and motor impairments in long-term survivors of
      hematopoietic stem cell transplantation performed in childhood: results from the
      Bone Marrow Transplant Survivor study.
AB  - BACKGROUND: Because of treatment-related toxicity, research is increasingly being
      focused on long-term sequelae secondary to hematopoietic stem cell
      transplantation (HSCT) in survivor populations. METHODS: This study describes the
      incidence of auditory, sensory, motor, and visual impairments, including
      cataracts, among 235 individuals who were treated with HSCT during childhood or
      adolescence. Outcomes were compared with 705 siblings of childhood cancer
      survivors. Participants completed a survey with questions on posttransplant organ
      system impairments. Approximately half of survivors were transplanted when
      younger than 10 years of age. The median length of followup was 11 years.
      RESULTS: The cumulative incidence of cataracts was 36% at 15 years post-HSCT,
      although cataracts occurred only in those who received total body irradiation as
      an HSCT conditioning agent or head irradiation before transplant. Persistent pain
      was reported by 21% of survivors. Loss of hearing in one or both ears, and legal
      blindness in one or both eyes, each occurred after transplant in 2% of survivors.
      Occurrences were uncommon, but survivors were 4.3 times (95% confidence interval
      [CI]: 2.0-9.4) more likely to report coordination problems, 7.7 times (95% CI:
      3.2-18.5) more likely to report chewing or swallowing problems, and 3.5 times
      (3.5; 95% CI: 1.6-7.9) more likely to report muscle weakness than those in the
      comparison group. Muscle weakness was strongly associated with positive history
      of chronic graft-versus-host disease. CONCLUSIONS: Increased risks were found for
      motor impairments, hearing loss, vision loss, and persistent pain among study
      participants. Cataracts were a frequent adverse effect, suggesting that close
      monitoring with appropriate intervention for preservation of vision, particularly
      among those who received total body irradiation, should be a primary goal in
      survivors of HSCT performed in childhood.

PMID- 16453336
TI  - Epidemiology of major depression in four cities in Mexico.
AB  - Analyses were conducted to estimate lifetime and current prevalence of major
      depressive disorder (MDD) for four representative cities of Mexico, to identify
      variables that influence the probability of MDD, and to further describe
      depression in Mexican culture. A multistage probability sampling design was used
      to draw a sample of 2,509 adults in four different regions of Mexico. MDD was
      assessed according to DSM-IV criteria by using the Composite International
      Diagnostic Interview collected by trained lay interviewers. The prevalence of MDD
      in these four cities averaged 12.8% for lifetime and 6.1% for the previous 12
      months. MDD was highly comorbid with other mental disorders. Women were more
      likely to have lifetime MDD than were men. Being divorced, separated, or widowed
      (compared to married or never married) and having experienced childhood trauma
      were related to higher lifetime prevalence but not to current prevalence. In
      addition, age and education level were related to current 12-month MDD. Data on
      the profile of MDD in urban Mexico are provided. This research expands our
      understanding of MDD across cultures.

PMID- 16453337
TI  - Electrochemically induced FTIR difference spectroscopy in the mid- to far
      infrared (200 microm) domain: a new setup for the analysis of metal-ligand
      interactions in redox proteins.
AB  - We report the setup of an electrochemical cell with chemical-vapor deposition
      diamond windows and the use of a Bruker 66 SX FTIR spectrometer equipped with
      DTGS and Si-bolometer detectors and KBr and mylar beam splitters, to record on
      the same sample, FTIR difference spectra corresponding to the structural changes
      associated with the change in redox state of active sites in proteins in the
      whole 1800-50 cm(-1) region. With cytochrome c we show that reliable reduced
      minus-oxidized FTIR difference spectra are obtained, which correspond to single
      molecular vibrations. Redox-sensitive IR modes of the cytochrome c are detected
      until 140 cm(-1) with a good signal to noise. This new setup is promising to
      analyze the infrared spectral region where metal-ligand vibrations are expected
      to contribute and to extend the analysis of vibrational properties to metal sites
      or redox states not accessible to (resonance) Raman spectroscopy.

PMID- 16453338
TI  - Mechanisms of the interaction between two ADAMTS13 gene mutations leading to
      severe deficiency of enzymatic activity.
AB  - The inherited deficiency of the von Willebrand factor-cleaving protease ADAMTS13
      is associated with rare forms of thrombotic thrombocytopenic purpura (TTP). We
      investigated a woman with a family history of chronic recurrent TTP and
      undetectable plasma levels of ADAMTS13 activity. Genetic analysis revealed two
      missense mutations in the heterozygous state: p.Val88Met substitution in the
      metalloprotease domain and p.Gly1239Val substitution in the first CUB domain of
      ADAMTS13. To explore the mechanism of ADAMTS13 deficiency in this patient, the
      wild type (WT; ADAMT13(WT)) and each mutant construct (ADAMTS13(Val88Met),
      ADAMTS13(Gly1239Val)) were transiently expressed in HEK 293 and COS-7 cells. To
      recapitulate the compound heterozygous state of the patient, both mutant ADAMTS13
      proteins were also expressed together. The p.Val88Met mutation led to a defect of
      secretion of the protease associated with a reduction of enzymatic activity, the
      p.Gly1239Val mutation led to a secretion defect causing intracellular
      accumulation of the protease. The mechanistic effects of the mutations were
      further explored by means of differential immunofluorescence, that demonstrated
      an homogeneous distribution of ADAMTS13(WT) in the Cis-Golgi and endoplasmic
      reticulum (ER) compartments, a reduction of ADAMTS13(Val88Met) in both
      compartments, while ADAMTS13(Gly1239Val) failed to reach the Cis-Golgi
      compartment and remained in the ER.

PMID- 16453339
TI  - Apolipoprotein (APOE) gene is associated with progression of age-related macular
      degeneration (AMD).
AB  - Progression of age-related macular degeneration (AMD), the leading cause of
      blindness in the elderly, was followed in a cohort of 238 individuals from a
      single center. Individuals with an epsilon (epsilon)2 genotype (c.526C>T of
      reference sequence NM_000041.2) of the apolipoprotein (APOE) gene were found to
      be strongly associated with disease with a significant 4.8-fold increased
      relative risk compared to individuals with an epsilon4 genotype (c.388T>C of
      reference sequence NM_000041.2) (odds ratio [OR], 4.8; 95% confidence interval
      [CI], 1.19-19.09) and a nearly significant three-fold increased relative risk
      compared to individuals with an epsilon3 genotype (reference sequence
      NM_000041.2) (OR, 2.8; 95% CI, 0.96-19.09). This finding was present only in
      females who progressed with AMD, which suggests that there may be a gender
      specific role in progression of AMD in individuals with an epsilon2 allele. A
      gender-related factor is therefore implicated either directly or indirectly in
      the AMD disease process.

PMID- 16453340
TI  - Canine ACL fibroblast integrin expression and cell alignment in response to
      cyclic tensile strain in three-dimensional collagen gels.
AB  - Tissue-engineered ligament substitutes have the potential to become an
      alternative graft source for ligament reconstruction. If this approach is to
      become viable, one must first understand and define the mechanisms responsible
      for creation, maintenance, and remodeling of the native anterior cruciate
      ligament. It is well accepted that mechanical load alters fibroblast phenotypic
      expression in a variety of cell sources; however, the mechanosensitive pathways
      responsible for alteration in matrix production, remodeling, and alignment are
      unknown. We hypothesize that cell surface integrins play a role in this
      mechanotransduction process, and as such respond to application of cyclic tensile
      load. Linear 3D collagen gels containing canine ACL fibroblasts were created in
      Flexercell Tissue-Train Culture Plates. Gels were untethered (control), tethered
      without external strain (tethered), or tethered and exposed to 2.5% cyclic strain
      for 2 h per day for 4 days (strain). Quantitation of alpha1, alpha5, and beta1
      integrin subunit was performed using flow cytometry. Cell and matrix alignment
      was studied using light, polarized light, and fluorescent microscopy. Expression
      of alpha5 and beta1 integrin subunits was increased significantly in fibroblasts
      in tethered and strained 3D collagen gels compared with the control, unloaded
      constructs (p < 0.05). These integrins are known to function as
      mechanotransducers in other tissues, implicating a similar role in
      mechanotransduction in ACL fibroblasts. Histologic analysis of the tethered and
      strained gels demonstrated a linear arrangement of cells and parallel collagen
      fibril architecture. In contrast, cell distribution and collagen alignment were
      disorganized in the control, unloaded gels. The alignment of cells and collagen
      in the 3D gels parallel to applied strain is similar to the in vivo state. These
      data add to our understanding of the behavior of ACL fibroblasts in vitro. The
      ability to manipulate signal transduction pathways may enhance our ability to
      engineer implantable ACL grafts or to modify ACL healing response.

PMID- 16453341
TI  - The effect of thrombin on ACL fibroblast interactions with collagen hydrogels.
AB  - Premature loss of provisional scaffold formation has been identified as one of
      the factors responsible for poor healing of intraarticular tissues. To address
      this deficiency, substitute provisional scaffolds are being developed. The
      function of these scaffolds can be enhanced by the addition of specific
      extracellular matrix proteins. In this study, it was hypothesized that the
      addition of thrombin to a provisional scaffold material would result in increases
      in cell proliferation, collagen production, and cell migration within the
      scaffold. These three parameters are thought to be critical components of wound
      healing. Gels containing fibrin and collagen supplemented with either 0, 10.5,
      21, or 42 U/mL of thrombin were placed in contact with explants of tissue from
      the anterior cruciate ligament. The addition of thrombin stimulated cell
      migration at low concentrations and impaired migration at higher concentrations,
      and had no significant effect on cell proliferation or collagen production. The
      use of all concentrations of thrombin resulted in mechanically weaker gels. Thus,
      the use of thrombin to optimize a collagen-platelet rich plasma (PRP) provisional
      scaffold must be done with caution, and use of high concentrations of thrombin
      (>42 IU/mL) should be avoided specifically in situations where gel strength or
      cell ingrowth is important. Use of low concentrations of thrombin (10.5 IU/mL)
      may be beneficial in applications where a faster set time and enhanced cell
      migration are desirable and the gel mechanical strength is of secondary
      importance.

PMID- 16453344
TI  - Cells seeded on MBG scaffold survive impaction grafting technique: Potential
      application of cell-seeded biomaterials for revision arthroplasty.
AB  - The objective of this study was to investigate the potential application of cell
      seeded biomaterials for revision arthroplasty and the reconstruction of major
      joints using the impaction grafting technique. Using morselized cancellous bone
      graft as a porous scaffold, MG63 cells were seeded on the scaffold and impacted
      into an acetabulum cup model using a mechanical device constructed from data
      obtained during impaction grafting by an orthopedic surgeon. Immediately after
      impaction, cells were trypsinized from the scaffold and processed for cell
      survival rates using the double-stranded DNA PicoGreen assay. Significant
      reductions in viable cells were observed between the fifth impact and both the
      first and second impacts (p < 0.01 and p < 0.05, respectively). Cell survival
      rate was 21.5% after five impacts. The biological performance of cell-seeded
      biomaterials may be enhanced by these surviving cells. Compared to allograft bone
      that is not osteogenic, a cell-seeded biomaterial might also be a suitable
      substitute for allograft bone for major joint reconstruction at revision
      arthroplasty.

PMID- 16453342
TI  - Osmolyte-induced protein folding free energy changes.
AB  - Upon addition of protecting osmolyte to an aqueous solution of an intrinsically
      unstructured protein, spectral observables are often seen to change in a sigmoid
      fashion as a function of increasing osmolyte concentration. Commonly, such data
      are analyzed using the linear extrapolation model (LEM), a method that defines a
      scale from 0%-100% folded species at each osmolyte concentration by means of
      extending pre- and post-folding baselines into the transition region. Defining
      the 0%-100% folding scale correctly for each osmolyte is an important part of the
      analysis, leading to evaluation of the fraction of folded protein existing in the
      absence of osmolytes. In this study, we used reduced and carboxyamidated RNase T1
      (RCAM-T1) as an intrinsically unstructured protein, and determined the
      thermodynamic stability of RCAM-T1 induced by naturally occurring osmolytes.
      Because the folded fraction of the protein population determined by experiments
      of thermal and urea-induced denaturation is nonzero in the absence of osmolytes
      at 15 degrees C, the commonly used LEM can lead to false values of DeltaG[stackD-
      >N0] for protein folding due to the arbitrary assumption that the protein is 100%
      unfolded in the presence of buffer alone. To correct this problem, titration of
      the protein solution with urea and extrapolating back to zero urea concentration
      gives the spectral value for 100% denatured protein. With fluorescence as the
      observable we redefine F/F0 to F/F0extrap = 1.0 and require that the denatured
      state baseline have this value as its intercept. By so doing, the 0%-100% scale
      corrected DeltaG[D-->N0] values of RCAM-T1 folding in the presence of various
      osmolytes are then found to be identical, with small error, demonstrating that
      DeltaG[D-->N0] is independent of the osmolytes used. Such a finding is an
      important step in validating this quantity derived from the LEM as having the
      properties expected of an authentic thermodynamic parameter. The rank order of
      osmolyte efficacies in stabilizing RCAM-T1 is sarcosine > sucrose > sorbitol >
      proline > betaine > glycerol.

PMID- 16453345
TI  - Effect of experimental suprascapular nerve block on active glenohumeral
      translations in vivo.
AB  - Static superior shoulder instability is associated with long-standing rotator
      cuff tears. Factors or mechanisms which can prevent superior migration of the
      humeral head, and therefore allow preservation or restoration of shoulder
      function despite nonanatomical cuff repair, are poorly understood. The question
      has therefore arisen, whether centering of the humeral head was the result of
      active shoulder muscle function. It was the goal of this experimental
      investigation to (1) determine the pattern of glenohumeral translations during
      active shoulder abduction measured by open-magnetic resonance imaging (MRI)
      techniques, and to (2) determine the influence of experimental paralysis of the
      infra- and supraspinatus muscles on these translations. In contrast to prior
      experimental investigations, the humeral head remained always centered in the
      glenoid fossa during active abduction. No superior migration of the humeral head
      could be provoked with experimental paralysis of the supra- and/or infraspinatus
      muscles. The hypothesis that static or dynamic superior humeral head displacement
      is prevented by active-supra- and/or infraspinatus muscle function must therefore
      be rejected, for the shoulder with a structurally intact muscle-tendon-bone unit.

PMID- 16453347
TI  - Identification of proteins adducted by reactive metabolites of naphthalene and 1
      nitronaphthalene in dissected airways of rhesus macaques.
AB  - Naphthalene and 1-nitronaphthalene are ambient air pollutants, which undergo P450
      dependent bioactivation in the lung. Reactive metabolites of naphthalene and 1
      nitronaphthalene covalently bind to proteins, and the formation of covalent
      adducts correlates with airway epithelial cell injury in rodent models. These
      studies were designed to identify protein adducts generated from these reactive
      metabolites within distal respiratory airways. Distal bronchioles and parenchyma
      from rhesus monkeys were incubated with [(14)C]naphthalene or [(14)C]1
      nitronaphthalene. Proteins were separated by 2-DE, blotted to PVDF membranes, and
      adducted proteins imaged by storage phosphor analysis. MS of in-gel tryptic
      digests identified numerous adducted proteins including: eight cytoskeletal
      proteins, two chaperone proteins, seven metabolic enzymes, one redox protein, two
      proteins involved in ion balance and cell signaling, and two extracellular
      proteins. While many proteins are adducted by both naphthalene and 1
      nitronaphthalene, some are unique to the individual toxicant and airway
      subcompartment. Although the role which adduction of these proteins plays in
      cytotoxicity was not evaluated, these studies provide candidate proteins for
      future work designed to determine the importance of protein adducts in the
      mechanisms of toxicity and for developing biomarkers useful in determining the
      relevance of findings in animal models to exposed human populations.

PMID- 16453348
TI  - Broad substrate specificity of ketoreductases derived from modular polyketide
      synthases.
AB  - Recombinant ketoreductase (KR) domains derived from antibiotic-producing modular
      polyketide synthases (PKSs) have been examined as potential catalysts for the
      enantioselective reduction of non-polyketide substrates. KR domains from two
      modular PKSs show significant activity toward alternative substrates,
      particularly those that incorporate cyclohexyl moieties. Through site-directed
      mutagenesis of the amino acid motifs previously implicated in stereocontrol by
      KRs, we have identified mutants with improved activity toward such compounds.
      These results suggest that PKS KRs could potentially be used as biotransformation
      catalysts for the production of chiral alcohols.

PMID- 16453350
TI  - Probing the molecular basis of protein function through chemistry.

PMID- 16453349
TI  - A caged uridine for the selective preparation of an RNA fold and determination of
      its refolding kinetics by real-time NMR.

PMID- 16453351
TI  - Polyelectrolyte templated polymerization in langmuir films: nanoscopic control of
      polymer chain organization.
AB  - Polyelectrolytes introduced in the aqueous subphase are shown to have a profound
      impact on the kinetics of polymerization of N-octadecylaniline at the air/water
      interface. This can be attributed to changes effected in molecular organization
      and reorientation behavior in the Langmuir film. The polyelectrolyte templates
      lead to considerable modification of the morphology of the monomer and polymer
      Langmuir films. Polyelectrolyte complexation is found to be an elegant and
      efficient methodology to achieve enhanced alignment of the polyaniline chains in
      the transferred Langmuir-Blodgett (Langmuir-Schafer) film.

PMID- 16453352
TI  - Mechanism of hydrolysis and aminolysis of homocysteine thiolactone.
AB  - Homocysteine thiolactone (tHcy) is deemed a risk factor for cardiovascular
      diseases and strokes, presumably because it acylates the side chain of protein
      lysine residues ("N-homocysteinylation"), thereby causing protein damage and
      autoimmune responses. We analysed the kinetics of hydrolysis and aminolysis of
      tHcy and two related thiolactones (gamma-thiobutyrolactone and N-trimethyl-tHcy),
      and we have thereby described the first detailed mechanism of thiolactone
      aminolysis. As opposed to the previously studied (thio and oxo)esters and
      (oxo)lactones, aminolysis of thiolactones was found to be first order with
      respect to amine concentration. Anchimeric assistance by the alpha-amino group of
      tHcy (through general acid/base catalysis) could not be detected, and the
      Bronsted plot (nucleophilicity versus pK(a)) for aminolysis yielded a slope
      (beta(nuc)) value of 0.66. These data support a mechanism of aminolysis where the
      rate-determining step is the formation of a zwitterionic tetrahedral
      intermediate. The beta(nuc) value and steric factors dictate a regime whereby, at
      physiological pH values (pH 7.4), maximal reactivity of tHcy is exhibited with
      primary amine groups with a pK(a) value of 7.7; this allows the reactivity of
      various protein amino groups towards N-homocysteinylation to be predicted.

PMID- 16453353
TI  - Phosphoramidite ligands in iridium-catalyzed allylic substitution.
AB  - A new phosphoramidite ligand was used in the iridium-catalyzed allylic
      substitution reaction. This permitted high regio- and enantioselectivities on a
      wide variety of substrates and nucleophiles. Because of the stereospecificity of
      the reaction obtained by using branched substrates, a kinetic resolution reaction
      was attempted. The origin of the impressive efficiency of this ligand in terms of
      kinetics was explored in detail, as was the role of the substituent in the ortho
      position of the amine moiety.

PMID- 16453354
TI  - Structural and magnetic studies of the tris(cyclopentadienyl)manganese(II)
      "paddle-wheel" anions [Cp(3-n)(MeCp)(n)Mn](-) (n=0-3, MeCp=C(5)H(4)CH(3),
      Cp=C(5)H(5)).
AB  - The ion-contact complexes [{(eta(5)-Cp)(2)Mn(eta(2):eta(5)-Cp)K}(3)]x0.5 THF
      (1x0.5 THF) and [{(eta(2)-Cp)(2)(eta(2);eta(5)-MeCp)MnK(thf)}]x2 THF (2x2 THF)
      and ion-separated complexes [Mg(thf)(6)][(eta(2)-Cp)(3)Mn](2) (3),
      [Mg(thf)(6)][(eta(2)-Cp)(eta(2)-MeCp)(2)Mn)](2)x0.5 THF (4x0.5 THF),
      [Mg(thf)(6)][(eta(2)-MeCp)(3)Mn)](2)x0.5 THF (5x0.5 THF) and [Li([12]crown
      4)](5)[(eta-Cp)(3)Mn](5) (6) (Cp=C(5)H(5), CpMe=C(5)H(4)CH(3)), have been
      prepared and structurally characterised. The effects of varying the Cp and CpMe
      ligands in complexes 1-5 have been probed by variable-temperature magnetic
      susceptibility measurements and EPR spectroscopic studies.

PMID- 16453355
TI  - Supramolecular switches based on the guanine-cytosine (GC) Watson-Crick pair:
      effect of neutral and ionic substituents.
AB  - We have theoretically analyzed Watson-Crick guanine-cytosine (GC) base pairs in
      which purine-C8 and/or pyrimidine-C6 positions carry a substituent X = NH(-),
      NH(2), NH(3) (+) (N series), O(-), OH, or OH(2) (+) (O series), using the
      generalized gradient approximation (GGA) of density functional theory at the
      BP86/TZ2P level. The purpose is to study the effects on structure and hydrogen
      bond strength if X= H is substituted by an anionic, neutral, or cationic
      substituent. We found that replacing X = H by a neutral substituent has
      relatively small effects. Introducing a charged substituent, on the other hand,
      led to substantial and characteristic changes in hydrogen-bond lengths,
      strengths, and hydrogen-bonding mechanism. In general, introducing an anionic
      substituent reduces the hydrogen-bond-donating and increases the hydrogen-bond
      accepting capabilities of a DNA base, and vice versa for a cationic substituent.
      Thus, along both the N and O series of substituents, the geometric shape and bond
      strength of our DNA base pair can be chemically switched between three states,
      thus yielding a chemically controlled supramolecular switch. Interestingly, the
      orbital-interaction component in some of these hydrogen bonds was found to
      contribute to more than 49 % of the attractive interactions and is thus virtually
      equal in magnitude to the electrostatic component, which provides the other
      (somewhat less than) 51 % of the attraction.

PMID- 16453356
TI  - Shape and spin state in four-coordinate transition-metal complexes: the case of
      the d(6) configuration.
AB  - Generalized polyhedral interconversion coordinates are defined within the
      framework of Avnir's continuous shape measures. The application of such
      interconversion coordinates to the study of the potential energy surfaces that
      define the stereochemical choice in four-coordinate transition metal complexes
      with different spin states is presented, and the correlation between potential
      energy curves and distribution of experimental structures along the tetrahedron
      to square interconversion path is shown for the case of the d(6) transition-metal
      complexes.

PMID- 16453357
TI  - Two chloride ions as a template in the formation of a cyclic hexaurea.

PMID- 16453358
TI  - Efficient gold-catalyzed hydroamination of 1,3-dienes.

PMID- 16453359
TI  - The ether lipid inositol-C2-PAF is a potent inhibitor of cell proliferation in
      HaCaT cells.
AB  - The search for specific anticancer drugs that do not interfere with DNA synthesis
      or influence the cytoskeleton has led to the development of modified
      phospholipids with antiproliferative properties. These compounds cause remodeling
      of the structure and function of plasma membranes. Recently, we described novel
      compounds, the glycosidated phospholipids, that surprisingly inhibit cell
      proliferation. These compounds contain alpha-D-glucose in the sn-2 position of
      the glycerol backbone of phosphatidylcholine (PC) and platelet-activating factor
      (PAF), which gives rise to 2-glucophosphatidylcholine (Glc-PC) and 1-O-octadecyl
      2-O-alpha-d-glucopyranosyl-sn-2-glycero-3-phosphatidylcholine (Glc-PAF),
      respectively. Glc-PC and Glc-PAF inhibit the growth of HaCaT cells at nontoxic
      concentrations. Here we report the introduction of myo-inositol, in place of
      alpha-D-glucose, in the sn-2 position of the glycerol backbone; this leads to two
      diastereomeric 1-O-octadecyl-2-O-(2-(myo-inositolyl)-ethyl)-sn-glycero-3-(R/S)
      phosphatidylcholines (Ino-C2-PAF). The inositol-containing PAF enhances the
      antiproliferative capacity (IC(50)=1.8 microM) and reduces the cytotoxicity
      relative to Glc-PAF (LC(50)=15 microM). Through biological assays, we showed
      that, in HaCaT cells, Ino-C2-PAF causes upregulation of the keratinocyte-specific
      differentiation marker involucrin, increases the activity of the differentiation
      marker transglutaminase, and induces apoptosis at nontoxic concentrations. Ino-C2
      PAF therefore seems to be a promising candidate for development as an
      antiproliferative drug for the treatment of hyperproliferative diseases of the
      skin.

PMID- 16453361
TI  - New principles in medicinal organometallic chemistry.

PMID- 16453362
TI  - Hybrid peptide hairpins containing alpha- and omega-amino acids: conformational
      analysis of decapeptides with unsubstituted beta-, gamma-, and delta-residues at
      positions 3 and 8.
AB  - The effects of inserting unsubstituted omega-amino acids into the strand segments
      of model beta-hairpin peptides was investigated by using four synthetic
      decapeptides, Boc-Leu-Val-Xxx-Val-D-Pro-Gly-Leu-Xxx-Val-Val-OMe: peptide 1
      (Xxx=Gly), peptide 2 (Xxx=betaGly=betahGly=homoglycine, beta-glycine), peptide 3
      (Xxx=gammaAbu=gamma-aminobutyric acid), peptide 4 (Xxx=deltaAva=delta
      aminovaleric acid). 1H NMR studies (500 MHz, methanol) reveal several critical
      cross-strand NOEs, providing evidence for beta-hairpin conformations in peptides
      2-4. In peptide 3, the NMR results support the formation of the nucleating turn,
      however, evidence for cross-strand registry is not detected. Single-crystal X-ray
      diffraction studies of peptide 3 reveal a beta-hairpin conformation for both
      molecules in the crystallographic asymmetric unit, stabilized by four cross
      strand hydrogen bonds, with the gammaAbu residues accommodated within the
      strands. The D-Pro-Gly segment in both molecules (A,B) adopts a type II' beta
      turn conformation. The circular dichroism spectrum for peptide 3 is characterized
      by a negative CD band at 229 nm, whereas for peptides 2 and 4, the negative band
      is centered at 225 nm, suggesting a correlation between the orientation of the
      amide units in the strand segments and the observed CD pattern.

PMID- 16453363
TI  - Preparation and structure of novel hexaazaisowurtzitane cages.
AB  - Hexaazaisowurtzitane or cage molecules have attracted attention concerning their
      synthesis because hexanitrohexaazaisowurtzitane (HNIW or CL20) is presently the
      most powerful energetic compound. The synthesis of hexaazaisowurtzitanes was
      considered to be limited solely to the condensation of certain benzylamines with
      glyoxal. Here, we present the synthesis and characterization of seven novel non
      benzylic hexaazaisowurtzitanes, such as hexapropargylhexaazaisowurtzitane. The
      substituents on the six nitrogen atoms are different to those of the benzyl or
      substituted benzyl groups to which previous syntheses were limited. X-ray
      structures are given for the hexapropargyl and hexa-2-thienylmethylene
      derivatives. Steric strains limit the synthesis with alpha-substituted benzyl and
      allyl derivatives. The reaction mechanism and the role of the intermediate
      diimines are discussed. Some of the novel hexaazaisowurtzitanes are potential
      precursors of hexanitrohexaazaisowurtzitane.

PMID- 16453364
TI  - Synthesis of fullerodendrons with an ammonium unit at the focal point and their
      cooperative self-assembly on a fluorescent ditopic crown ether receptor.
AB  - Dendritic branches with 1, 2, or 4 peripheral fullerene subunits and an ammonium
      function at the focal point have been prepared. Their ability to form self
      assembled dendritic structures with oligophenylenevinylene receptors bearing one
      or two crown ether moieties has been evidenced by ES-MS studies for the first
      time. These supramolecular complexes are multicomponent photoactive devices in
      which the emission of the central receptor is dramatically quenched by the
      fullerene units. This new property resulting from the association of the
      different molecular subunits allowed detailed investigations of the self-assembly
      process by means of fluorescence titrations. The binding studies have revealed
      positive cooperative effects for the assembly of the fullerodendrimers with the
      ditopic receptor. Interestingly, the stability of the supramolecular 2:1
      structures increases as the size of the dendritic unit increases. This positive
      dendritic effect has been explained by the larger number of possible
      intramolecular fullerene-fullerene interactions between the two dendritic guests
      when the number of fullerene subunits is increased.

PMID- 16453365
TI  - Self-assembled structures with liquid-crystalline order in aqueous solution by
      patterning poly(phenylene ethynylene)s.
AB  - Facially amphiphilic (FA) phenylene ethynylene (PE) polymers that self-assemble
      in aqueous solution were studied by small-angle X-ray diffraction (SAXD) and
      found to self-assemble into bilayers with a fully extended backbone. The
      resulting bilayers have long-range liquid-crystalline order. This self-assembly
      is programmed into the molecule by placing polar and nonpolar groups at precise
      locations so that they segregate onto opposite sides of the molecular structure.
      The absence of FA patterning generated an amorphous sample confirming the
      importance of this programmed amphiphilicity in the self-assembly process.
      Facially amphiphilic patterning represents a new design criterion for
      supramolecular chemistry, illustrated here in the observation of molecular
      ordering into bilayers reminiscent of self-assembled structures commonly found in
      biology, including amphiphilic beta-sheet polypeptides and phospholipid bilayers.

PMID- 16453367
TI  - Selective oxidation of alkanes with molecular oxygen and acetaldehyde in
      compressed (supercritical) carbon dioxide as reaction medium.
AB  - The oxidation of cycloalkanes or alkylarenes with molecular oxygen and
      acetaldehyde as sacrificial co-reductant occurs efficiently in compressed
      (supercritical) carbon dioxide (scCO2) under mild multiphase conditions. No
      catalyst is required and high-pressure ATR-FTIR online measurements show that a
      radical reaction pathway is heterogeneously initiated by the stainless steel of
      the reactor walls. For secondary carbon atoms, high ketone to alcohol ratios are
      observed (3.5-7.9), most probably due to fast consecutive oxidation of alcoholic
      intermediates. Since C--C scission reactions are detected only to a very small
      extent, tertiary carbon atoms are transformed into the corresponding alcohols
      with high selectivity. Detailed analysis of the product distributions and other
      mechanistic evidence suggest that acetaldehyde acts not only as the sacrificial
      oxygen acceptor, but also as an efficient H-atom donor for peroxo and oxo
      radicals and as a crucial reductant for hydroperoxo intermediates. In comparison
      to other inert gases such as compressed N2 or Ar, the use of carbon dioxide was
      shown to increase the yields of alkane oxygenates under identical reaction
      conditions.

PMID- 16453366
TI  - The interplay of inverted redox potentials and aromaticity in the oxidized states
      of new pi-electron donors: 9-(1,3-dithiol-2-ylidene)fluorene and 9-(1,3-dithiol-2
      ylidene)thioxanthene derivatives.
AB  - Derivatives of 9-(1,3-dithiol-2-ylidene)fluorene (9) and 9-(1,3-dithiol-2
      ylidene)thioxanthene (10) have been synthesised using Horner-Wadsworth-Emmons
      reactions of (1,3-dithiol-2-yl)phosphonate reagents with fluorenone and
      thioxanthen-9-one. X-ray crystallography, solution electrochemistry, optical
      spectroscopy, spectroelectrochemistry and simultaneous electrochemistry and
      electron paramagnetic resonance (SEEPR), combined with theoretical calculations
      performed at the B3P86/6-31G** level, elucidate the interplay of the electronic
      and structural properties in these molecules. These compounds are strong two
      electron donors, and the oxidation potentials depend on the electronic structure
      of the oxidised state. Two, single-electron oxidations (E(1)ox < E(1)ox) were
      observed for 9-(1,3-dithiol-2-ylidene)fluorene systems (9). In contrast,
      derivatives of 9-(1,3-dithiol-2-ylidene)thioxanthene (10) display the unusual
      phenomenon of inverted potentials (E(1)ox > E(1)ox) resulting in a single, two
      electron oxidation process. The latter is due to the aromatic structure of the
      thioxanthenium cation (formed on the loss of a second electron), which stabilises
      the dication state (10(2+)) compared with the radical cation. This contrasts with
      the nonaromatic structure of the fluorenium cation of system 9. The two-electron
      oxidation wave in the thioxanthene derivatives is split into two separate one
      electron waves in the corresponding sulfoxide and sulfone derivatives 27-29 owing
      to destabilisation of the dication state.

PMID- 16453368
TI  - Impact of prior choice on local Bayes factors for cluster detection.
AB  - In this paper, we evaluate the usefulness of local Bayes factors as a tool for
      spatial cluster detection. In particular, we consider whether local Bayes factors
      from models with a fixed, but overly large number of clusters can consistently
      identify the evidence for clustering for a variety of prior specifications for
      the cluster locations. We also investigate the robustness of the local Bayes
      factor to the number of clusters included in the model. We explore the impacts of
      prior choice for cluster location and the number of clusters on posterior
      inference for disease rates. We conduct the comparison by analysing data on 1990
      breast cancer incidence in Wisconsin.

PMID- 16453369
TI  - Likelihood based tests for spatial randomness.
AB  - Many different methods have been proposed to test the spatial randomness of a
      point pattern adjusting for an inhomogeneous background population. These tests
      can be classified into cluster detection tests, concerned with the detection and
      inference of local clusters, and global clustering tests, which collect evidence
      for clustering throughout the study region. This paper is mainly concerned about
      global clustering tests. Some tests for spatial randomness are based on
      likelihoods, which include the spatial and space-time scan statistics with
      variable window size and Gangnon and Clayton's weighted average likelihood ratio
      tests. Both of these tests perform well compared to other tests for cluster
      detection and global clustering, respectively. In this study, we develop other
      likelihood based tests for global clustering and we explore the use of different
      weight functions with these tests. The power of these tests is evaluated using
      simulated data set and compared with existing methods.

PMID- 16453370
TI  - Cluster detection diagnostics for small area health data: with reference to
      evaluation of local likelihood models.
AB  - The focus of this paper is the development of a range of cluster detection
      diagnostics that can be used to assess the degree to which a clustering method
      recovers the true clustering behaviour of small area data. The diagnostics
      proposed range from individual region specific diagnostics to neighbourhood
      diagnostics, and assume either individual region risk as focus, or concern areas
      of maps defined to be clustered and the recovery ability of methods. A simulation
      based comparison is made between a small set of count data models: local
      likelihood, BYM and Lawson and Clark. It is found that local likelihood has good
      performance across a range of criteria when a CAR prior is assumed for the lasso
      parameter.

PMID- 16453371
TI  - A workflow spatial scan statistic.
AB  - We propose a modification of the spatial scan statistic that takes account of
      workflow, which is the movement of individuals between home and work. The
      objective is to detect clusters of disease in situations where exposure occurs in
      the workplace, but only home address is available for analysis. In these
      situations, application of the usual spatial scan statistic does not account for
      possible differences between home and work address, thereby reducing the power of
      detection. We describe an extension to the usual spatial scan statistic that uses
      workflow data to search for disease clusters resulting from workplace exposure.
      We also present results from simulations that demonstrate the increased power of
      the workflow scan statistic over the usual scan statistic for detecting clusters
      arising from exposures in the workplace.

PMID- 16453372
TI  - The geography of power: statistical performance of tests of clusters and
      clustering in heterogeneous populations.
AB  - Heterogeneous population densities complicate comparisons of statistical power
      between hypothesis tests evaluating spatial clusters or clustering of disease.
      Specifically, the location of a cluster within a heterogeneously distributed
      population at risk impacts power properties, complicating comparisons of tests,
      and allowing one to map spatial variations in statistical power for different
      tests. Such maps provide insight into the overall power of a particular test, and
      also indicate areas within the study area where tests are more or less likely to
      detect the same local increase in relative risk. While such maps are largely
      driven by local sample size, we also find differences due to features of the
      statistics themselves. We illustrate these concepts using two tests: Tango's
      index of clustering and the spatial scan statistic. Furthermore, assessments of
      the accuracy of the 'most likely cluster' involve not only statistical power, but
      also spatial accuracy in identifying the location of a true underlying cluster.
      We illustrate these concepts via induction of artificial clusters within the
      observed incidence of severe cardiac birth defects in Santa Clara County, CA in
      1981.

PMID- 16453373
TI  - Multiscale detection of localized anomalous structure in aggregate disease
      incidence data.
AB  - We present a modelling framework for detection of potentially anomalous structure
      in aggregate spatial disease incidence data in a manner sensitive to localization
      at multiple scales and/or positions. The key technical contribution is the re
      casting of the components of a multiscale disease mapping methodology, recently
      introduced by the authors in an earlier paper, into a form appropriate for
      hypothesis testing. In particular, we describe how hypotheses of spatially
      clustered variations in disease incidence may be linked in one-to-one
      correspondence with collections of hypotheses on the values of certain multiscale
      parameters associated with a user-defined hierarchy of nested partitions of an
      overall spatial region. A Bayesian hypothesis testing methodology is developed in
      the context of a standard Poisson measurement model, over the collection of
      possible multiscale hypotheses. We discuss the specification of hyper parameters
      and prior distributions on the space of models. The methodology is illustrated on
      both simulated and real data.

PMID- 16453374
TI  - Statistical methods for the detection of spatial clustering in case-control data.
AB  - In this paper, I develop new approaches for the detection of spatial clustering
      in case-control data. One method is based upon drawing Thiessen polygons around
      each control. It is unnecessary to actually draw or compute the boundaries of the
      polygons; it is sufficient to count, for each control, the number of cases that
      are closer to that control than to any other control. A second method is similar
      to the Cuzick-Edwards method, which is based on counts of cases that are among
      the k-nearest neighbours of cases, but is instead based upon the number of cases
      within a specified distance of cases. These first two methods are global methods
      in the sense that they provide a single statistic that measures the degree of
      spatial clustering. The third method suggests a local statistic, for tests of the
      null hypothesis of no spatial clustering around a prespecified focus. The method
      is based upon the cumulative chi2 test, which is typically used to test whether
      cases are more prevalent than expected around a prespecified location. This is
      also extended to the case where all observational locations are considered as
      potential cluster locations and multiple testing is carried out. Each of the new
      methods is illustrated using data on childhood leukaemia and lymphoma cases in
      North Humberside.

PMID- 16453375
TI  - Evaluating spatial surveillance: detection of known outbreaks in real data.
AB  - Since the anthrax attacks of October 2001 and the SARS outbreaks of recent years,
      there has been an increasing interest in developing surveillance systems to aid
      in the early detection of such illness. Systems have been established which do
      this is by monitoring primary health-care visits, pharmacy sales, absenteeism
      records, and other non-traditional sources of data. While many resources have
      been invested in establishing such systems, relatively little effort has as yet
      been expended in evaluating their performance. One way to evaluate a given
      surveillance system is to compare the signals it generates with known outbreaks
      identified in other systems. In public health practice, for example, public
      health departments investigate reports of illness and sometimes track hospital
      admissions. Comparison of new systems with extant systems cannot generate
      estimates of test characteristics such as sensitivity and specificity, since the
      actual number of positives and negatives cannot be known. However, the comparison
      can reveal whether a new or proposed system's signals match outbreaks detected by
      the existing system. This could help support or reject the new system as an
      alternative or complement to the extant system. We propose three methods to test
      the null hypothesis that the new system does not signal true outbreaks more often
      than would be expected by chance. The methods differ in the restrictiveness of
      the assumptions required. Each test may detect weaknesses in the new system,
      depending on the distribution of outbreaks and can be used to construct
      confidence limits on the agreement between the new system's signals and the
      outbreaks, given the distribution of the signals. They can be used to assess
      whether the new system works in that it detects the outbreaks better than chance
      would suggest and can also determine if the new systems' signals are generated
      earlier than an extant system.

PMID- 16453376
TI  - Fast detection of arbitrarily shaped disease clusters.
AB  - Disease cluster detection and evaluation have commonly used spatial statistics
      methods that scan the map with a fixed circular window to locate candidate
      clusters. Recently, there has been interest in searching for clusters with
      arbitrary shape. The circular scan test retains high power of detecting a
      cluster, but does not necessarily identify the exact regions contained in a non
      circular cluster particularly well. We propose, implement and evaluate a new
      procedure that is fast and produces clusters estimates of arbitrary shape in a
      rich class of possible cluster candidates. We showed that our methods contain the
      so-called upper level set method as a particular case. We present a power study
      of our method and, among other results, the main conclusion is that the
      likelihood-based arbitrarily shaped scan method is not appropriate to find a
      cluster estimate. When the parameter space includes the set of all possible
      spatial clusters in a map, a large and discrete parameter space, maximum likely
      cluster estimates tend to overestimate the true cluster by a large extent. This
      calls for a new approach different from the maximum likelihood method for this
      important public health problem.

PMID- 16453377
TI  - Disease cluster detection: a critique and a Bayesian proposal.
AB  - This paper reviews issues in the analysis of non-focussed clustering, and
      proposes a novel approach to cluster modelling that can be used in a surveillance
      context. The novel approach involves the use of local likelihood models for the
      analysis of clustering in small area health data. Local likelihood is used when
      interdependence between data events at locations is modelled directly, as opposed
      to the modelling of a hidden process of cluster centres. This approach allows the
      use of conventional posterior sampling. It also allows a less parameterized
      approach to the form of clusters detected. The idea of a spatially dependent
      lasso which provides the local maxima for the aggregation of locations is
      considered as an approximation. The methods are applied to a well known data set
      and compared with Satscan, and a conditional logistic Bayesian model.

PMID- 16453379
TI  - An extended power of cluster detection tests.
AB  - Several tests have been proposed to detect spatial disease clustering without
      prior information on their locations. In order to compare the performance of
      these tests, most authors employ the usual power, i.e. the rejection probability
      of the null hypothesis of no clustering due to various reasons. However, the
      usual power is not always appropriate for evaluating the cluster detection tests
      since their purpose is to both reject the null hypothesis and identify the
      cluster areas accurately. In this paper, we propose an extended power of the
      cluster detection tests, which includes the usual power as a special case.
      Further, we define the profile of the extended power, which can be expected to
      play an important role in the evaluation and comparison of several cluster
      detection tests. The proposed extended power and its profile are demonstrated by
      two tests--Kulldorff's circular spatial scan statistic and a flexible spatial
      scan statistic proposed by Tango and Takahashi.

PMID- 16453380
TI  - A cluster model for space-time disease counts.
AB  - Modelling disease clustering over space and time can be helpful in providing
      indications of possible exposures and planning corresponding public health
      practices. Though a considerable number of studies focus on modelling spatio
      temporal patterns of disease, most of them do not directly model a spatio
      temporal clustering structure and could be ineffective for detecting clusters. In
      this paper, we extend a purely spatial cluster model to accommodate space-time
      clustering. Inference is performed in a Bayesian framework using reversible jump
      Markov chain Monte Carlo. This idea is illustrated using data on female breast
      cancer mortality from Japan. A hierarchical parametric space-time model for
      mapping disease is used for comparison.

PMID- 16453381
TI  - Constant and intermittent high glucose enhances endothelial cell apoptosis
      through mitochondrial superoxide overproduction.
AB  - BACKGROUND: It has been previously shown that hyperglycemia enhances free radical
      production, inducing oxidative damage, which in its turn activates the death
      pathways implicated in cell apoptosis and necrosis. But the possible involvement
      of this pathway in the hyperglycemia-induced apoptosis of endothelial cells has
      not yet been reported. METHODS: To verify a possible connection between
      mitochondrial ROS production and apoptosis induced by both stable and oscillating
      high glucose, SOD, MnTBAP and TTFA was added to HUVEC cell culture medium. We
      measured nitrotyrosine and 8OHdG as oxidative stress parameters and Bcl-2
      expression and Caspase-3 expression and activity as apoptosis indicators.
      RESULTS: Our results show that hyperglycemia, both stable or oscillating,
      increases oxidative stress and endothelial cell apoptosis through ROS
      overproduction at the mitochondrial transport chain level. CONCLUSION: The
      prevention of mitochondrial oxidative damage seems to be a future important
      therapeutic strategy in diabetes.

PMID- 16453382
TI  - No evidence for a major effect of two common polymorphisms of the catalase gene
      in type 1 diabetes susceptibility.
AB  - BACKGROUND: Type 1 diabetes (T1D) is a multifactorial disease, the genetic
      analysis of which has yielded few true positive linkage and association results.
      Replication of association in independent, large-sample studies is essential to
      further identify the genes involved in T1D. Two single nucleotide polymorphisms
      (SNPs) in the catalase gene have been reported to be associated with T1D.
      METHODS: Major effects of two SNPs, C1167T (rs769217) and C(-262)T (rs1001179),
      of the catalase gene on T1D susceptibility have been reported previously in
      Russians from Moscow. We genotyped C1167T and C(-262)T in large family (1642
      families) and British case-control (3530 cases and 3930 controls) collections and
      tested for association with T1D. RESULTS: We found no evidence of an association
      between T1D and C1167T or C(-262)T in either the family or case-control
      collections, or for the D11S2008 microsatellite polymorphism in families.
      However, we did find limited statistical evidence of an association at C1167T in
      USA families (P = 0.033; RR for 1167C = 1.23, 95% CI = 1.02-1.49) and C(-262)T in
      UK families (P = 0.046; RR for (-262)C = 0.86, 95% CI = 0.75-0.99). CONCLUSION:
      We found no evidence for a major effect of C1167T or C(-262)T on T1D
      susceptibility in two large sample collections. Limited statistical evidence of
      an association at C1167T in USA families and C(-262)T in UK families was found,
      but these results are likely to be false positives. The previously reported
      association of these SNPs may also have been a false positive, or a population
      specific association in Russians from Moscow.

PMID- 16453383
TI  - Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG):
      prime role of MOG44F in selection and control of MOG-reactive T cells in H-2b
      mice.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is an important myelin target antigen,
      and MOG-induced EAE is now a widely used model for multiple sclerosis. Clonal
      dissection revealed that MOG-induced EAE in H-2(b) mice is associated with
      activation of an unexpectedly large number of T cell clones reactive against the
      encephalitogenic epitope MOG35-55. These clones expressed extremely diverse TCR
      with no obvious CDR3alpha/CDR3beta motif(s). Despite extensive TCR diversity, the
      cells required MOG40-48 as their common core epitope and shared MOG44F as their
      major TCR contact. Fine epitope-specificity analysis with progressively truncated
      peptides suggested that the extensive TCR heterogeneity is mostly related to
      differential recognition of multiple overlapping epitopes nested within MOG37-52,
      each comprised of a MOG40-48 core flanked at the N- and/or the C-terminus by a
      variable number of residues important for interaction with different TCR.
      Abrogation of both the encephalitogenic potential of MOG and T cell reactivity
      against MOG by a single mutation (MOG44F/MOG44A), together with effective down
      regulation of MOG-induced EAE by MOG37-44A-52, confirmed in vivo the primary role
      for MOG44F in the selection/activation of MOG-reactive T cells. We suggest that
      such a highly focused T cell autoreactivity could be a selective force that
      offsets the extensive TCR diversity to facilitate a more "centralized control" of
      pathogenic MOG-related T cell autoimmunity.

PMID- 16453385
TI  - Pathogen-specific TLR signaling in mucosa: mutual contribution of microbial TLR
      agonists and virulence factors.
AB  - Detection of microorganisms through microbe-associated molecular patterns (MAMP)
      by Toll-like receptors (TLR) is crucial to trigger protective immunity. In the
      mucosa, sentinel cells are exposed to MAMP from both pathogens and commensals;
      however, the TLR response is tightly controlled to avoid inflammation in response
      to commensals. Uropathogenic Escherichia coli (UPEC) trigger innate responses
      during urinary tract infection in a TLR4-dependent and CD14-independent manner.
      UPEC express virulence factors, such as type 1 fimbriae and/or P fimbriae,
      allowing bacterial attachment to the epithelium. In this issue of the European
      Journal of Immunology, Fisher et al. show that fimbriae are required to induce a
      TLR4-specific epithelial response. Depending on the fimbriae expressed by UPEC,
      different adaptor molecules are involved in TLR4 signaling. These data add to the
      recent body of evidence suggesting that TLR responses are regulated by co
      receptors, such as receptors for virulence factors. In conclusion, the
      "pathogenic" TLR stimulation provides a novel way for the host to ignore
      commensal bacteria.

PMID- 16453386
TI  - Induced peripheral regulatory T cells: the family grows larger.
AB  - In order to control immune reactions and to prevent autoimmunity, the immune
      system relies on a multitude of regulatory T cells (Treg). Most work in this
      field has focussed on Treg of the CD4(+) T cell subset because of the central
      role CD4(+) T cells play as initiators and regulators of immune responses. One
      discovery of particular importance was the identification of naturally occurring
      CD4(+)CD25(+) Treg that arise in the thymus and express the transcription factor
      Foxp3; however, Treg can also be induced in the periphery after immune
      activation. A paper in this issue of the European Journal of Immunology
      identifies a novel type of induced murine CD8(+) Treg that arise in TCR HY
      transgenic female mice after injection of MHC class I tetramers loaded with HY
      peptide. These Treg prevent subsequent rejection of male skin grafts suggesting
      that their manipulation may represent a new way of improving graft rejections
      against minor histocompatibility barriers.

PMID- 16453387
TI  - Endogenous cortisol determines the circadian rhythm of lipopolysaccharide-- but
      not lipoteichoic acid--inducible cytokine release.
AB  - To investigate the circadian rhythm of inducible cytokine release and a potential
      pacemaker role of endogenous cortisol, cortisol levels as well as cytokine
      release from ex vivo LPS-stimulated blood were assessed at 4-h intervals over 24
      h in 11 volunteers. We found a significant diurnal variation for IFN-gamma and IL
      8, and a tendency for TNF, all inversely correlated to the serum cortisol levels,
      but no evidence for such a rhythm for IL-1beta and IL-6. In vitro IC(50) values
      for cytokine inhibition by hydrocortisone (HC) corresponded to the observed rank
      order for circadian rhythmicity. mRNA analyses revealed that this was due to a
      reduction of gene transcription. These effects of HC were significantly reversed
      by the glucocorticoid receptor antagonist RU486. Supplementation of HC in vivo to
      maintain morning cortisol levels throughout the day blunted the circadian rhythm
      of ex vivo LPS-induced cytokines. Surprisingly, no significant diurnal variation
      for any investigated cytokine was found in the same volunteer group upon
      stimulation with lipoteichoic acid (LTA), the gram-positive counterpart to LPS.
      Furthermore, 10-50-fold higher HC concentrations as compared to LPS were required
      to block LTA-induced cytokine release. LTA, in contrast to LPS, failed to
      activate Jun kinase, a reported target for HC action.

PMID- 16453388
TI  - Phosphorylated and nonphosphorylated epitopes of the La/SSB autoantigen:
      comparison of their antigenic and conformational characteristics.
AB  - La/SSB phosphoprotein is the target antigen of autoantibodies in sera of patients
      with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). Among other
      structural and function motifs, four phosphorylation sites are encompassed in the
      primary sequence of La/SSB. Two of them (Thr-362 and Ser-366) are located within
      GSGKGKVQFQGKKTKFASDD (346-368) and one (Thr-302) within VTWEVLEGEVEKEALKKI (301
      318), which are main B-cell epitopes of La/SSB. With the aim to investigate how
      phosphorylation, one of the most common posttranslational protein modifications,
      affects the antigenic and conformational characteristics of the La/SSB epitopes,
      we synthesized and studied the phosphorylated epitopes La/SSB(346-368)-P,
      La/SSB(359-368)-P, and La/SSB(301-318)-P with respect to their nonphosphorylated
      counterparts. Anti-La/SSB positive sera from SS and SLE patients are better
      recognized by the phosphorylated epitopes compared to their nonphosphorylated
      counterparts. Conformational analysis by (1)H nuclear magnetic resonance
      spectroscopy and molecular dynamics showed that the phosphorylated epitopes adopt
      different structural characteristics from those of the corresponding
      nonphosphorylated epitopes. It is concluded that phosphorylation can create
      neoepitopes with altered functions, compared to the nonphosphorylated epitopes,
      which might be seen from the immune system as "foreign."

PMID- 16453389
TI  - Electrospray ionization mass spectrometry: a key analytical tool for the
      characterization of regioselectively derivatized maltooligosaccharides obtained
      starting from natural beta-cyclodextrin.
AB  - The development of natural cyclodextrins (CDs) for various industrial
      applications (agroalimentary, cosmetic or pharmaceutical) constitutes a
      continuous challenge. For the integration of these agricultural plant products in
      the creation of super-absorbent biodegradable and hypoallergenic materials (water
      retaining agents, cosmetic hydrating and texturing, pharmaceutical and
      horticultural products) to replace synthetic polymers, we have developed chemical
      methods to access regioselectively C-6-derivatized maltooligosaccharides starting
      from CDs. These compounds are highly suitable for further chemical modifications
      and are expected to give access to a new class of polymeric materials with
      potential applications such as water-retaining agents in the disposable nappies
      industry. For the structural analysis of carbohydrates, electrospray ionization
      mass spectrometry (ESI-MS) offers precise results, analytical versatility and
      very high sensitivity. We report herein the rapid and convenient follow-up of
      chemical reactions, the purity evaluation of intermediates and final products,
      and the structural characterization of derivatized maltooligosaccharides,
      obtained by acidic cleavage (acetolysis) of halogenated and esterified CDs, using
      ESI-MS in combination with the high-resolution (HRMS) and tandem mass
      spectrometry (MS/MS) capabilities of a quadrupole orthogonal time-of-flight (Q
      TOF) mass spectrometer.

PMID- 16453391
TI  - Product recalls. Recalls: Chuck E. Cheese's plastic siren whistles...girl's
      sleepwear sold at J.C. Penney stores...and doorway baby jumpers.

PMID- 16453390
TI  - Synthesis and characterization of new biodegradable hyaluronan alkyl derivatives.
AB  - Several new biocompatible and degradable materials were prepared by chemical
      modification of sodium hyaluronate. The method of activation of hyaluronate by
      cyanogen bromide was used and subsequent reaction with nucleophile led to the
      formation of carbamate. This modification of hydroxyl groups of
      glycosaminoglycans preserves the carboxyl groups and retains properties of
      polyelectrolyte. This method affords derivatives easily and the reaction
      condition correlates with degree of substitution. The experimental results show
      the effect of reaction conditions (reaction time, ratio of reactants) and effect
      of substitution on biodegradability. The obtained materials were characterized by
      nuclear magnetic resonance and Fourier transform infrared spectroscopy.

PMID- 16453392
TI  - Speaking in tongues.

PMID- 16453393
TI  - Dream big.

PMID- 16453394
TI  - Back to high school.

PMID- 16453395
TI  - Manipulating a journal article.

PMID- 16453396
TI  - As a face transplant heals, flurries of questions arise; doctors differ on ethics
      and patient's mental state.

PMID- 16453397
TI  - Clone scientist relied on peers and Korean pride.

PMID- 16453398
TI  - Human cloning was all faked, Koreans report.

PMID- 16453399
TI  - Drug maker's efforts to compete in lucrative insulin market are under scrutiny.

PMID- 16453400
TI  - Health care in the Baltic states.

PMID- 16453401
TI  - Improving heart health in Europe.

PMID- 16453402
TI  - Authors, reviewers and editors at The EMBO Journal.

PMID- 16453403
TI  - The TL-DNA in octopine crown-gall tumours codes for seven well-defined
      polyadenylated transcripts.
AB  - Seven polyadenylated transcripts of significantly different relative abundance
      were detected in octopine crown-gall tissue after gel electrophoretic separation
      and subsequent transfer to diazobenzyloxymethyl paper. The transcripts range from
      670 to 2700 bases long. The different transcripts were located using 19 different
      fragments of the TL-region as probes. By hybridizing labelled RNA to separated
      complementary strands of the T-DNA, and parallel determination of the chemical
      polarity of the strands, the 5' - 3' orientations of six of the seven transcripts
      was identified. Both strands of the T-DNA code RNA. Hybridization of octopine TL
      DNA against poly A RNA's present in two nopaline tumour-lines C58-S1 and BT37,
      and vice versa, reveals a minimum of two and possibly four transcripts common to
      both octopine and nopaline tumours. These transcripts originate from
      corresponding parts of the conserved region of the T-DNA and are of similar size.

PMID- 16453404
TI  - Genetic Identification of functions of TL-DNA transcripts in octopine crown
      galls.
AB  - The TL-DNA in octopine crown galls encodes seven transcripts most, if not all,
      expressed from individual promoters. Site-specific deletions and substitutions in
      the T-region of the octopine plasmid pTiB6S3 indicate some of the functions of
      the TL-DNA transcripts. Two of the seven genes are sufficient to allow tumorous
      growth. T-DNA transfer and oncogenicity are controlled by different and
      independently acting functions. None of the transcripts of TL-DNA appear to be
      essential for T-DNA transfer. Four, possibly five, of the TL-DNA transcripts act
      by suppressing organ development. Shoot and root formation are suppressed by the
      action of different transcripts.

PMID- 16453405
TI  - An unusual evolutionary behaviour of a sea urchin histone gene cluster.
AB  - DNA sequences of cloned histone coding sequences and spacers of sea urchin
      species that diverged long ago in evolution were compared. The highly repeated H4
      and H3 genes active during early embryogenesis had evolved (in their silent
      sites) at a rate (0.5-0.6% base changes/Myr) similar to single-copy protein
      coding genes and nearly as fast as spacer DNA (0.7% base changes/Myr) and unique
      DNA. Thus, evolution in the major histone genes conforms to a universal
      evolutionary clock based on the rate of base sequence change. By contrast, the H4
      and H3 coding sequences and a non-transcribed spacer of the DNA clone h19 of
      Psammechinus miliaris show an exceptionally low rate of sequence evolution only
      1/100 to 1/200 that predicted from the clock hypothesis. According to the
      classical model of gene inheritance, the h19 DNA sequences in the Psammechinus
      genome require unusual conservation mechanisms by selection at the level of the
      gene and spacer sequences. An alternative explanation could be recent horizontal
      gene transfer of a histone gene cluster from the very distantly related
      Strongylocentrotus drobachiensis to the P. miliaris genome.

PMID- 16453406
TI  - Analysis of models of irregular shape by solution X-ray scattering: the case of
      the 50S ribosomal subunit from E. coli.
AB  - Structural models of biological macromolecules can be tested by comparing
      calculated and experimental solution scattering curves. We have developed an
      approach for computing scattering shape functions at medium resolution from
      models proposed on the basis of other techniques such as electron microscopy. We
      present the results obtained with the 50S ribosomal subunit from Escherichia
      coli; two models are considered, one proposed by Lake (1976), the other one by
      Tischendorf et al. (1975). Although the two models are similar in many respects,
      their scattering shape functions are significantly different. The comparison with
      the experimental scattering curve allows us to check the scale of the models and,
      after scaling, to quantitate the agreement between the observed and the
      calculated curves. Finally, it can provide a starting point for the structural
      interpretation of the X-ray data.

PMID- 16453407
TI  - Multiplicity and diversity of cloned zein cDNA sequences and their chromosomal
      localisation.
AB  - We have constructed and screened cDNA libraries from total maize endosperm
      poly(A) RNA or from a mRNA fraction enriched in zein sequences. From these
      libraries we have isolated clones representative of the major classes of zein
      cDNA sequences and have characterised them by crosshybridisation, by hybrid
      selected translation, by in situ hybridisation to maize chromosomes, and
      hybridisation to genomic Southern blots. We conclude that at least four types of
      non cross-hybridising zein sequences are present, two coding for light chains and
      two for heavy chains. At least in the case of the light zeins, there is
      considerable sequence diversity among the clones which hybridise to each type.
      Similar results are obtained by translation of the mRNAs selected by each clone.
      In situ hybridisation shows that the light chain zein genes are located on
      chromosomes 4, 7, and 10, whilst genes coding for some of the heavy chain zeins
      are confined to the distal part of the long arm of chromosome 4.

PMID- 16453408
TI  - Electron microscopic visualization of a discrete class of giant translation units
      in salivary gland cells of Chironomus tentans.
AB  - Lysates were made of whole salivary glands from Chironomus tentans and electron
      microscopic spreads prepared according to Miller and Beatty (1969). The
      sedimented material consisted mainly of ribosomes, most of which were present in
      giant polysomes which showed gradients of material protruding laterally from the
      ribosomes, interpreted as nascent polypeptide chains. Each giant polysome
      contained one such gradient. On the basis of the presence of a small group of
      terminal ribosomes without nascent chains at the 3' end, 19 apparently complete
      polysomes were selected, representing a discrete class of polysomes containing
      between 66 and 92 ribosomes (79 +/- 7, m +/- s.d.). Arguments are presented that
      they constitute the translation units for giant secretory proteins coded by RNA
      from the large Balbiani rings, BR1 and BR2.

PMID- 16453409
TI  - Catalytic effects of elongation factor Ts on polypeptide synthesis.
AB  - The kinetic parameters which characterize the interaction between elongation
      factor Tu (EF-Tu) and elongation factor Ts (EF-Ts) have been determined in a
      poly(uridylic acid)-primed translation system. The EF-Ts catalyzed release of GDP
      from EF-Tu was measured independently in a nucleotide exchange assay. We conclude
      that the rate-limiting step for the EF-Tu cycle in protein synthesis in the
      absence of EF-Ts is the release of GDP. By adding EF-Ts the time of this step is
      reduced from 90 s to 30 ms. Half maximal rate is obtained at an EF-Ts
      concentration of 2.5 x 10 M.

PMID- 16453410
TI  - Halobacterium halobium phage oH.
AB  - Phage oH, a novel virus of the archaebacterium Halobacterium halobium, resembles
      in size and morphology two other Halobacterium phages. One-step growth curves
      show a 5.5 h eclipse, a latent period of 7 h, and an apparent burst size of 170.
      Phage oH contains linear, double-stranded DNA which has a molecular weight of 39
      x 10 and a GC content of 65%. A packaging model accounting for the partial
      circular permutation and terminal redundancy of oH DNA is suggested. Partial
      homology of oH DNA with the DNA of H. halobium, predominantly with the AT-rich
      satellite DNA, was observed. The presence of minor restriction fragments of oH
      DNA which could be removed by purification of phage from single plaques suggests
      the existence of phage variants with rearranged DNA. A strain of H. halobium
      containing oH DNA was isolated which is resistant to infection by phage oH.

PMID- 16453411
TI  - Molecular cloning of the white locus region of Drosophila melanogaster using a
      large transposable element.
AB  - We report the molecular cloning of a chromosome segment including the white locus
      of Drosophila melanogaster. This region was isolated using a deficiency extending
      from the previously cloned heat-shock puff sequences at 87A7 to a large
      transposable element containing the loci white and roughest.FB-NOF, a 7.5 kb
      element with partial homology to a family of inverted repeat sequences (Potter et
      al., 1980), is found very near the deficiency breakpoint, and is followed by DNA
      originating from the white locus region. Sequences totalling 60 kb surrounding
      this initial entry point were obtained by the cloning of successively overlapping
      fragments from a wild-type strain. Several rearrangement breakpoints have been
      mapped relative to the cloned DNA; these define the limits of the white locus and
      further differentiate the "white proximal region", thought to function in gene
      regulation, from the remainder of the locus. Insertion of the dispersed
      repetitive element copia into the white locus is observed in strains carrying the
      white-apricot allele. Analysis of several white-apricot revertants suggests that
      copia insertion is responsible for the apricot eye color phenotype.

PMID- 16453413
TI  - Functional expression of individual plasmid-coded RNA bacteriophage MS2 genes.
AB  - The genes of the RNA-containing bacteriophage MS2 were individually inserted into
      thermoinducible expression plasmids under control of the phage lambda P(L)
      promoter. Three phage-coded proteins (A-protein, coat protein, and replicase)
      were expressed at high efficiency. Induced cultures specifically complemented
      superinfecting amber mutants of phage MS2. Regulatory mechanisms operative during
      the natural infection cycle of the phage were reproduced by the plasmid
      expression system.

PMID- 16453412
TI  - Pleiotropic effect of his gene mutations on nitrogen fixation in Klebsiella
      pneumoniae.
AB  - Several his mutations were found to influence nitrogen fixation in Klebsiella
      pneumoniae: hisB, hisC, and hisD mutants had 50% of wild-type levels of
      nitrogenase activity when supplied with 30 mug or less histidine/ml although this
      concentration did not limit protein synthesis and the mutants retained a Nif
      plate phenotype. A hisA mutation had a similar but more dramatic effect. At low
      concentrations of histidine the hisA mutant strain had only 5% of the nitrogenase
      activity found at high histidine concentration or in a his strain, and was also
      Nif on low histidine agar plates. Addition of adenine restored nitrogenase
      activity in the hisA but not the hisB, hisC, or hisD mutants. Low levels of
      intracellular ATP, a consequence of hisG enzyme activity, correlated with loss of
      nitrogen-fixing ability in the hisA mutant which failed to sustain nif gene
      expression under these conditions. Synthesis of other major cell proteins was
      relatively unaffected indicating that nif gene expression is selectively
      regulated by the energy status of the organism.

PMID- 16453414
TI  - The DNA-binding protein of Pf1 filamentous bacteriophage: amino-acid sequence and
      structure of the gene.
AB  - The amino-acid sequence of the single-stranded DNA-binding protein of
      bacteriophage Pf1 and the nucleotide sequence of the corresponding gene have been
      determined. The protein has 144 amino acids and a molecular weight of 15 400; the
      gene consists of 435 nucleotides. The amino-acid sequence was determined by Edman
      degradation, carboxypeptidase A, B, and P digestion of intact protein and of
      peptides derived by chymotrypsin, Staphylococcus aureus V8 protease, and trypsin
      digestion. The nucleotide sequence was determined by the dideoxy method after
      random cloning of fragments of Pf1 DNA into M13. No sequence homology could be
      established between the amino-acid sequence of the DNA-binding protein of
      Pseudomonas aeruginosa-specific bacteriophage Pf1 and bacteriophage fd of
      Escherichia coli.

PMID- 16453415
TI  - The tRNA-like structure of turnip yellow mosaic virus RNA: structural
      organization of the last 159 nucleotides from the 3' OH terminus.
AB  - The secondary structure of the isolated tRNA-like sequence (n=159) present at the
      3' OH terminus of turnip yellow mosaic virus RNA has been established from
      partial nuclease digestion with S1 nuclease and T1, CL(3), and Naja oxiana
      RNases. The fragment folds into a 6-armed structure with two main domains. The
      first domain, of loose structure and nearest the 5' OH terminus, is composed of
      one large arm which extends into the coat protein cistron. The second, more
      compact domain, is composed of the five other arms and most probably contains the
      structure recognized by valyl-tRNA synthetase. In this domain three successive
      arms strikingly resemble the T[unk], anticodon, and D arms found in tRNA. Near
      the amino-acid accepting terminus, however, there is a new stem and loop region
      not found in standard tRNA. This secondary structure is compatible with a L
      shaped three-dimensional organization in which the corner of the L and the
      anticodon-containing limb are similar to, and the amino-acid accepting region
      different from, that in tRNA. Ethylnitrosourea accessibility studies have shown
      similar tertiary structure features in the T[unk] loop of tRNA and in the
      homologous region of the viral RNA.

PMID- 16453416
TI  - Nucleotide sequences of yeast genes for tRNA(2), tRNA(2) and tRNA(1): homology
      blocks occur in the vicinity of different tRNA genes.
AB  - Three members of a collection of pBR322-yeast DNA recombinant plasmids containing
      yeast tRNA genes have been analyzed and sequenced. Each plasmid carries a single
      tRNA gene: pY44, tRNA(2); pY41, tRNA(2); pY7, tRNA(1). All three genes are
      intronless and terminate in a cluster of Ts in the non-coding strand. The
      sequence information here and previously determined sequences allow an extensive
      comparison of the regions flanking several yeast tRNA genes. This analysis has
      revealed novel features in tRNA gene arrangement. Blocks of homology in the
      flanking regions were found between the tRNA genes of an isoacceptor family but,
      more interestingly, also between genes coding for tRNAs of different amino-acid
      specificities. Particularly, three examples are discussed in which sequence
      elements in the neighborhood of different tRNA genes have been conserved to a
      high degree and over long distances.

PMID- 16453417
TI  - The structure of tandem regulatory regions in the deo operon of Escherichia coli
      K12.
AB  - The transcription initiation sites of the deo operon of Escherichia coli K12 have
      been determined in vitro and in vivo. Initiation of transcription occurs at two,
      tandemly arranged, homologous regions which are located 600 base pairs apart from
      each other. Evidence for a novel regulation mechanism of deo gene expression
      involving the deoR repressor is presented.

PMID- 16453418
TI  - Convergent transcription interferes with expression of the copy number control
      gene, copA, from plasmid R1.
AB  - The copy number control gene, copA, of plasmid R1 codes for an 80-nucleotide
      untranslatable RNA. In Escherichia coli minicells, some copA hybrid plasmids and
      R1 miniplasmids also express a transcript of 200 nucleotides. Only the small RNA
      mediates the CopA phenotype. The switch between 80- and 200-nucleotide RNA
      synthesis is shown to be caused by convergent transcription; if transcription
      proceeds in both directions the inactive larger RNA is synthesised; the active
      small RNA is formed when copA transcription is not opposed by transcription from
      the other direction. The data presented indicate that convergent transcription
      interferes with copA expression by abolishing or reducing normal copA
      transcription termination.

PMID- 16453419
TI  - Ligand binding and stereochemical effects in hemocyanins.
AB  - The Bohr effect in the binding of O(2) and CO to Helix pomatia beta-hemocyanin
      has been estimated by the potentiometric titration method. On the basis of the
      results, as well as other information available, we conclude that binding of O(2)
      to hemocyanin is associated with a quaternary allosteric transition (T-->R),
      while binding of CO is not. This conclusion is in agreement with previous
      results, which indicate that homotropic interactions are observed only for the
      binding of O(2) to the active site of hemocyanins. This is in marked contrast to
      the behaviour of hemoglobins which, otherwise, share with hemocyanins a number of
      important features, in spite of basic chemical differences. The stereochemical
      requirements of O(2), which forms a bridge between the two copper atoms in a
      site, have to be considered essential for the onset of cooperativity in
      hemocyanins.

PMID- 16453421
TI  - Human papillomavirus 1a complete DNA sequence: a novel type of genome
      organization among Papovaviridae.
AB  - [This corrects the article on p. 231 in vol. 1, PMID: 6325156.].

PMID- 16453420
TI  - Genetic analysis of nitrogen fixation in a tropical fast-growing Rhizobium.
AB  - The Rhizobium strain ORS571, which is associated with the tropical legume
      Sesbania rostrata, has the property of growing in the free-living state at the
      expense of ammonia or N(2) as sole nitrogen source. Five mutants, isolated as
      unable to form colonies on plates under conditions of nitrogen fixation, were
      studied. All of them, which appear as Fixin planta, are nif mutants. With mutant
      5740, nitrogenase activity of the crude extract was restored by addition of pure
      Mo-Fe protein of Klebsiella pneumoniae. A 13-kb BamHI DNA fragment from the wild
      type strain, which hybridized with a probe carrying the nifHDK genes of K.
      pneumoniae, was cloned in vector pRK290 to yield plasmid pRS1. The extent of
      homology between the probe and the BamHI fragment was estimated at 4 kb and
      hybridization with K. pneumoniae nifH, nifK, and possibly nifD was detected. The
      pRS1 plasmid was introduced into the sesbania rhizobium nif mutants. Genetic
      complementation was observed with strain 5740(pRS1) both in the free-living state
      and in planta. It thus appears that biochemistry and genetics of nitrogen
      fixation in this particular Rhizobium strain can be performed with bacteria grown
      under non-symbiotic conditions.

PMID- 16453422
TI  - A candidate gene for human U1 RNA.
AB  - [This corrects the article on p. 133 in vol. 1, PMID: 6201353.].

PMID- 16453423
TI  - Constant and variable parts in the Balbiani ring 2 repeat unit and the
      translation termination region.
AB  - The large Balbiani rings of the chironomids produce giant internally repeated
      transcripts that are translated into silk-like proteins used for protective
      tubes. We have cloned fragments of the Balbiani ring 2 (BR2) gene of Chironomus
      pallidivittatus, normally the most prominent BR, for sequencing and restriction
      analysis. The results indicate a basic, tandemly arranged repeat unit of 198 bp,
      consisting of an invariant region of 102 bp followed by a variable region of 96
      bp, the latter containing short internal tandem repeats. In the coding strand of
      both regions, there is a tendency to maximize adenine ( 40%) and minimize
      cytosine + thymidine (32-33%). Stringency in codon usage and absence of
      preference for third position nucleotide substitutions between homologous
      sequences suggest selection at the nucleotide level to be important. Both regions
      code for peptides rich in basic amino acids, but show distinct differences in
      other coding properties. The invariant region probably codes for a crystalline
      domain, and the variable region for a proline-rich, amorphous domain. One of the
      clones includes the 3' end of the translated region. Surrounding and following
      two stop codons is a sequence of four short palindromes. Furthermore, the first
      stop codon is part of a sequence reminiscent of a "TATA box". The possibilities
      are discussed that this area of the gene might be a target for regulatory
      molecules controlling translation termination and/or the expression of an
      overlapping cistron.

PMID- 16453424
TI  - Monoclonal antibodies against contact sites A of Dictyostelium discoideum:
      detection of modifications of the glycoprotein in tunicamycin-treated cells.
AB  - Tunicamycin acts on cell aggregation in Dictyostelium discoideum by changing cell
      movement and by inhibiting the EDTA-stable type of intercellular adhesion.
      Tunicamycin-treated cells show unco-ordinated pseudopodial activity such that
      pseudopods are simultaneously extended from all parts of the cell surface, and
      the cells are unable to move in straight paths. Concurrent with the inhibition of
      formation of EDTA-stable contacts, N-glycosylation of a glycoprotein specific for
      aggregation-competent cells is inhibited. This glycoprotein, previously called
      contact site A, has an apparent mol. wt. of 80 kilodaltons (kd). In membranes of
      tunicamycin-treated cells, two components are detected that react with certain
      monoclonal antibodies against contact sites A: one component of 66 kd, the other
      of 53 kd apparent mol. wt. Another group of monoclonal antibodies reacts only
      with the 80-kd glycoprotein and the 66-kd component. These results are in accord
      with the assumption that the glycoprotein carries two carbohydrate chains, and
      that the antibodies differ in their requirement for glycosylation of the antigen.
      Despite the coincidence between blockage of EDTA-stable cell adhesion and
      inhibited glycosylation of contact sites A, direct involvement of the
      carbohydrate moieties of this glycoprotein in intercellular adhesion seems
      questionable. EDTA-stable cell adhesion has not been blocked by Fab fragments
      from antibodies that specifically react with the glycosylated protein.

PMID- 16453425
TI  - Electron microscopic mapping of monoclonal antibodies on the tail region of
      Dictyostelium myosin.
AB  - The binding sites of five monoclonal antibodies against myosin of Dictyostelium
      discoideum have been mapped. These antibodies bind to the tail region of the
      myosin molecule. By rotary shadowing, images of myosin-antibody complexes were
      obtained in which the mean distance of the midpoint of an antibody molecule from
      the myosin heads was localized with a precision better than 2 nm (90% confidence
      limit). Other quantitative data extracted from electron micrographs provided
      information on the stoichiometry of antibody-myosin interaction. Certain
      antibodies interacted with myosin molecules only at a ratio of 1:1. Other
      antibodies formed complexes of two molecules bound to homologous sites on a
      double-stranded myosin tail. Affinities were estimated and the abilities of
      different antibodies to cross-connect two myosin molecules were evaluated.

PMID- 16453426
TI  - Turnip yellow mosaic virus RNA is aminoacylated in vivo in Chinese cabbage
      leaves.
AB  - Turnip yellow mosaic virus (TYMV) contains a tRNA-like structure as an integral
      part of its genome. This structure is located at the extreme 3' end of the viral
      RNA and is the acceptor of valine after 3'-terminal adenylation. It is known that
      in vitro (with bacterial, yeast, or plant systems) and in vivo (upon
      microinjection into Xenopus laevis oocytes) a series of tRNA-specific enzymes can
      recognize this structure in the viral RNA. We report that TYMV RNA is valylated
      and consequently adenylated in vivo in its natural host, Chinese cabbage leaves.
      This suggests that the acylated form of the viral RNA could play an important
      role in the life-cycle of the virus.

PMID- 16453427
TI  - Identification by immunoprecipitation of cauliflower mosaic virus in vitro major
      translation product with a specific serum against viroplasm protein.
AB  - A highly specific antiserum was prepared against purified cauliflower mosaic
      virus viroplasm-protein (VmP). A virus specific in vitro major translation
      product (TPmaj), encoded by the 19S poly(A) RNA fraction from cauliflower mosaic
      virus infected turnip leaves, was recognized by this antiserum. The N-terminal
      sequence of TPmaj corresponds to the sequence following the first in-phase
      initiation codon in gene VI of the cauliflower mosaic virus genome. Both VmP and
      TPmaj have blocked termini and probably start from the same AUG codon.

PMID- 16453428
TI  - Rearrangements of the 5S RNA gene cluster of Drosophila melanogaster associated
      with the insertion of a B104 element.
AB  - The organization of the 5S RNA gene cluster of Drosophila melanogaster is
      different in two Oregon R stocks that have been separated for a number of years.
      The Oregon R Yale population contains various different arrangements of the
      cluster. One of these is due to the insertion of a B104 element near one end of
      the cluster. Other arrangements lack the B104 insertion and have instead a
      variety of deletions originating in the vicinity of the B104 insertion site and
      removing from 0 to 60% of the 5S RNA genes without affecting nearby tRNA genes.
      In contrast, the Oregon R Heidelberg population has no B104 element in the 5S
      gene cluster and no heterogeneity in the arrangement of the cluster. We propose
      that transposable elements inserted at a genomic locus generate heterogeneity in
      a population at that locus due to excision of the element with and without
      accompanying deletions of flanking sequences. As a consequence, a fly population
      would accumulate a large number of deletions scattered throughout the genome in
      as many loci as contain transposable elements. We show further that D.
      melanogaster contains a large redundancy of 5S RNA genes since the 60% deletion
      of the cluster shows no visible phenotype when homozygous or when heterozygous
      against a total deletion of the entire 5S gene cluster.

PMID- 16453429
TI  - Origin of replication in chloroplast DNA of Euglena gracilis located close to the
      region of variable size.
AB  - Chloroplast DNA (cpDNA), containing 10% replicative molecules, was isolated 2 h
      after onset of the dark period from cultures of Euglena gracilis strain Z. The
      DNA was digested with the restriction enzymes PvuII, SalI, BamHI, or EcoRI.
      Fragments that contained intact replicative loops were measured to determine the
      position of replicated sequences in relation to the restriction enzyme sites. It
      was found that replication starts at a unique position near one of the
      palindromic sequences I(2) (Koller and Delius, 1982a) which is located upstream
      (with respect to the direction of rRNA transcription) of the AT-rich region of
      variable size (Jenni et al., 1981; Schlunegger et al., in preparation). In the
      majority of cases DNA synthesis proceeds unidirectionally away from this region
      for 5000 nucleotides before it starts in the other direction (in the same sense
      as the rRNA transcription) through the Z-region and the second palindromic
      sequence.

PMID- 16453430
TI  - A plasmid in the archaebacterium Sulfolobus acidocaldarius.
AB  - A plasmid of mol. wt. approximately 9 x 10 has been isolated from the
      archaebacterium Sulfolobus acidocaldarius strain B12. Plasmid production is
      induced by u.v. radiation. A copy of the plasmid is probably carried by the
      chromosome, integrated at a specific site. The entire plasmid, and also
      restriction fragments of it, has been cloned into Escherichia coli plasmid
      vectors, and the cleavage sites on the plasmid DNA of three restriction
      endonucleases have been mapped.

PMID- 16453431
TI  - A cAMP-dependent protein kinase is present in differentiating Dictyostelium
      discoideum cells.
AB  - We demonstrate the occurrence of a cAMP-dependent protein kinase in Dictyostelium
      discoideum cells at the terminal stage of differentiation. A cAMP-binding
      component was purified to homogeneity by affinity chromatography. This subunit
      inhibits the activity of purified catalytic subunit from beef heart protein
      kinase; the inhibition is reversed upon addition of cAMP. The protein is highly
      specific for cAMP and has a dissociation constant of 4 nM. The isolated
      regulatory subunit is a monomer of 39 K, with a sedimentation coefficient of 3.5S
      and a frictional coefficient of 1.24. The differences between this regulatory
      subunit and regulatory subunits of protein kinases from other sources are
      discussed.

PMID- 16453432
TI  - Cloning and analysis of a genomic fragment of Dictyostelium discoideum
      hybridizing to an RNA specifically accumulated in spore cells.
AB  - A marker for Dictyostelium discoideum spore RNA differentiation has been isolated
      from a genomic DNA library by differential screening and a recombinant plasmid
      containing a genomic sequence complementary to spore specific RNA has been
      characterized. Only a small portion ( approximately 1 kb) of the 4.7-kb genomic
      insert is transcribed. The genomic organization of this spore specific gene shows
      a unique sequence flanked by reiterated sequences.

PMID- 16453433
TI  - A prokaryotic tRNA gene, inactive in Xenopus laevis oocytes, is activated by
      recombination with an eukaryotic tRNA gene.
AB  - [This corrects the article on p. 817 in vol. 1, PMID: 6329706.].

PMID- 16453435
TI  - DNA map of mutations at the scute locus of Drosophila melanogaster.
AB  - The achaete-scute gene complex (AS-C) of Drosophila melanogaster is involved in
      the differentiation of innervated elements in the adult (chaetes) and in the
      embryo (central nervous system). Genetically, the AS-C is subdivided into four
      regions: achaete, scute alpha, lethal of scute, and scute beta. Using a
      previously cloned fragment of scute DNA, we have now cloned 62 kb of wild-type
      DNA from the scute region. No repetitive sequences have been detected in this
      stretch of DNA. Of 16 scute mutants with chromosomal rearrangements studied
      (inversions, deletions, and translocations), nine, included genetically in scute
      beta, have breakpoints in the cloned region. The remaining rearrangements, which
      genetically correspond to scute alpha, map outside and to the left of the cloned
      region. Of nine scute ;point mutants' studied, eight have large DNA alterations
      within the cloned region. These alterations include insertions (five) and
      deletions (three). The DNA alterations found in both ;point mutants' and
      rearrangements are interspersed and scattered over 40 kb. The relationship
      between the sites of the DNA alterations and the mutant phenotypes are discussed.

PMID- 16453434
TI  - Isolation and characterization of the retinal-binding component of halorhodopsin.
AB  - Halorhodopsin (HR) was reconstituted in cell vesicles prepared from Halobacterium
      halobium strain L-07 by addition of tritium-labelled retinal and subsequently
      reduced with cyanoborohydride. Lysis of the labelled vesicles in water and
      dissolution of the cell membranes with 4% SDS allowed the purification of the
      retinyl protein (RP) by a 3-step procedure. Gel filtration on AcA-44 ultrogel was
      followed by chromatography on hydroxylapatite and preparative SDS-polyacrylamide
      gel electrophoresis. This procedure yielded material which migrated as a single
      band of an apparent mol. wt. of 25 000 on analytical SDS-polyacrylamide gels. The
      purification was 400-fold with an overall yield of 15%. Not only the mol. wts.
      but also the amino acid compositions of the RPs from bacteriorhodopsin (BR) and
      HR are very similar. Polyclonal antibodies against BR and HR did not, however,
      crossreact. When the two RPs were partially digested with staphylococcal V8
      protease the proteolytic pattern of the retinyl peptides was similar, but not
      identical: two extra peptides are present in BR. The same kind of differences
      were found in the h.p.l.c. elution profiles of retinyl peptides produced by
      subtilisin digestion. Therefore, the two proteins must be different gene products
      and not modification products of one and the same protein.

PMID- 16453436
TI  - Characterization and crystal packing of three-dimensional bacteriorhodopsin
      crystals.
AB  - The three-dimensional crystals of the integral membrane protein bacteriorhodopsin
      have been characterized by X-ray diffraction and freeze-fracture electron
      microscopy: the needle-like form A crystals belong to space group P 1
      (pseudohexagonal) with seven molecules per crystallographic unit cell forming one
      turn of a non-crystallographic helix. The probable arrangement of the
      bacteriorhodopsin molecules is derived from freeze-fracture electron micrographs
      and chromophore orientation. Membrane-like structures are not present. The same
      helices of bacteriorhodopsin molecules found in crystal form A also make up the
      cube-like crystal form B. They are now arranged in all three mutually
      perpendicular directions. These cubes are always highly disordered, since the
      unit cell length corresponds to 6.7 molecules of the 7-fold helix. Very often,
      conversion of bacteriorhodopsin from the three-dimensional crystals into
      filamentous material occurs.

PMID- 16453437
TI  - Segmental differences in the protein content of Drosophila imaginal discs.
AB  - The protein content of various Drosophila imaginal discs was analysed by two
      dimensional electrophoresis followed by silver-staining. Three proteins,
      identified as tropomyosins alpha and beta and actin I, are more abundant in the
      metathoracic discs (haltere and third leg) than in the mesothoracic discs (wing
      and second leg). In the case of the wing disc, these proteins are probably
      contributed by the adepithelial (muscle precursor) cells, as indicated by their
      non-uniform localisation within the disc. Mutations in the bithorax complex have
      no effect on the difference between second and third leg discs. We conclude that
      there is a segmental difference in the protein content of homologous discs, that
      this difference is probably localized in the adepithelial cells, and that it is
      not under the direct control of known alleles of the bithorax complex.

PMID- 16453438
TI  - Genomic clones of a wild-type allele and a transposable element-induced mutant
      allele of the sucrose synthase gene of Zea mays L.
AB  - In an attempt to isolate the transposable genetic element Ds from Zea mays L., we
      cloned DNA fragments hybridizing to a cDNA clone derived from the sucrose
      synthase gene in a lambda vector (lambda::Zm Sh). The fragments cloned from wild
      type and from the Ds-induced mutant sh-m5933 (lambda::Zm sh-m5933) share a
      segment 6 kb long while a contiguous segment of 15 kb of lambda::Zm sh-m5933
      (mutant-derived DNA) does not hybridize to the DNA segment cloned from the wild
      type. Restriction maps are given, and the junction point between the two DNA
      segments in the mutant clone was determined. Hybridization of DNA fragments,
      present in the wild-type DNA of lambda::Zm Sh, but not in the mutant clone,
      lambda::Zm sh-m5933, to genomic DNA of sh-m5933 showed that no part of this DNA
      is deleted. It cannot be said whether the DNA found in the mutant, but not in the
      wild-type clone, has been brought there by Ds insertion or by another Ds
      dependent DNA rearrangement. The mutant-derived DNA was hybridized to genomic DNA
      of various maize lines digested by several restriction endonucleases.
      Approximately 40 bands were detected. The mutant-derived DNA contains two pairs
      of inverted repeats several hundred nucleotide pairs long, one of which is
      located at the junction to wild-type-derived DNA.

PMID- 16453439
TI  - Light-stimulated transcription of genes for two chloroplast polypeptides in
      isolated pea leaf nuclei.
AB  - Nuclei isolated from both light-grown and dark-grown leaves of Pisum sativum by
      Percoll density gradient centrifugation incorporate labelled UTP into RNA when
      supplemented with the other three nucleoside triphosphates. The RNA is
      heterodisperse, with transcripts up to at least 25S in size. Among these
      transcripts are sequences hybridizing to cloned DNA probes for wheat rRNA and two
      abundant chloroplast polypeptides of Pisum, viz. the small subunit of ribulose
      bisphosphate carboxylase and a polypeptide of the light-harvesting chlorophyll
      a/b binding complex. Transcription of small subunit and light-harvesting complex
      sequences is greater (18-fold and 9-fold, respectively) in nuclei from light
      grown leaves than in nuclei from dark-grown leaves. Transcription of ribosomal
      genes, by contrast, is only doubled by growth in the light. Small subunit and
      light-harvesting complex sequences transcribed in dark-grown nuclei are not
      degraded in a 120 min chase. These results suggest that the stimulation of
      accumulation of small subunit and light-harvesting complex mRNAs by exposure of
      Pisum seedlings to light is mediated by an increase in transcription rather than
      by a decrease in RNA degradation.

PMID- 16453441
TI  - Patch homologies and the integration of adenovirus DNA in mammalian cells.
AB  - [This corrects the article on p. 1101 in vol. 1.].

PMID- 16453440
TI  - A homologous repetitive block structure underlies the heterogeneity of heavy and
      light chain zein genes.
AB  - Heavy and light chain zein genes from maize, affected by different regulatory
      loci, are related in sequence and structure. The two kinds of genes code for a
      signal peptide, a head region of 67 amino acids, six and a half to eight
      repetitive blocks of 20 amino acids each and a short tail piece. This block
      structure would allow inter or intragenic recombination giving rise to
      heterogeneous zein genes. Length variation in zein polypeptides is also due to
      the occurrence of termination mutations within some genes. Homology between heavy
      and light chain zein genes extends to the flanking sequences where a short region
      at the 5' end of the transcript can base pair with the 3' end and may have
      regulatory implications.

PMID- 16453442
TI  - Sex determination and dosage compensation in Drosophila melanogaster: production
      of male clones in XX females.
AB  - Sex determination and dosage compensation in Drosophila are implemented by the
      ratio of X-chromosomes to sets of autosomes (X:A ratio). Our aim was to change
      this X:A ratio during development, and to assess the response of the affected
      cells in sexually dimorphic structures. For this purpose, clones of XO
      constitution were produced in female embryos and larvae of two genotypes in which
      almost the entire euchromatic arm of one X-chromosome was translocated to the
      third chromosome. Genotype I was heterozygous for the X-linked recessive
      mutations Sxl, genotype II was homozygous for Sxl. The Sxl gene (sex-lethal) is
      involved in mediating sex determination and dosage compensation. In genotype I
      (Sxl), male clones could be generated up to 48 h in genitalia and analia, up to
      72 h in the sex comb region and up to 96 h in 5th and 6th tergites. In genotype
      II (Sxl), male clones only appeared in the tergites, and only up to 24 h. The
      difference in these results is ascribed to the presence of Sxl in genotype I:
      when homozygous, this mutation causes XX clones to differentiate male structures;
      most of the male clones produced in genotype I must therefore be XX. In contrast,
      male clones produced in genotype II must be XO. Since these were only found when
      generated in embryos we conclude that the X:A ratio expresses itself autonomously
      in clones by setting the state of activity of the Sxl gene around blastoderm
      stage. Once this is achieved, the X:A signal is no longer needed, and the state
      of activity of the Sxl gene determines sex and dosage compensation.

PMID- 16453443
TI  - Identification of an endogenous plasmid in Dictyostelium discoideum.
AB  - A plasmid has been discovered in a strain of the eukaryote, Dictyostelium
      discoideum, which has an unstable, non-chromosomal, cobalt resistance phenotype.
      The plasmid, termed Ddp1, is 13.5 kbp in size and is found in the nucleus. It has
      an A-T content typical of Dictyostelium DNA as judged by its restriction enzyme
      digestion pattern, and it is not related to either mitochondrial or ribosomal
      DNA. Similar or identical plasmids have been found in two original, cobalt
      sensitive, isolates, NC4 and V12, but no plasmid was detected in three other
      isolates (WS472, WS526, WS584). The plasmid codes for non-essential functions
      since it is absent from the latter isolates, and it is lost from mutant strains
      which are capable of axenic growth.

PMID- 16453444
TI  - Delta sequences in the 5' non-coding region of yeast tRNA genes.
AB  - Two so far undetected tRNA genes were found close to delta (delta) sequences at
      the sup4 locus on chromosome X in the genome of Saccharomyces cerevisiae. The two
      genes were identified from their abundant transcription products in frog oocytes.
      Hybridisation experiments allowed the mapping of the transcripts in cloned DNA
      and DNA sequence analysis revealed the presence of one AGGtRNA and one GACtRNA
      gene. tRNA genes with sequences similar or identical to GACtRNA exist in 14-16
      copies per haploid yeast genome, whereas only one copy was detected for AGGtRNA.
      In vivo labelling of total yeast tRNA with P followed by hybridisation revealed
      that the unique AGGtRNA gene is transcribed in S. cerevisiae. delta sequences are
      present 120 bp upstream from the first coding nucleotide in the case of AGGtRNA,
      80 bp in the case of GACtRNA and 405 bp in the case of the known UACtRNA (sup4)
      gene. delta sequences, as part of Ty elements or alone, were also found by other
      investigators at similar distances upstream of the mRNA start in mutant alleles
      of protein-coding yeast genes. Although protein-coding genes are transcribed by
      RNA polymerase II and tRNA genes by RNA polymerase III, the 5' non-coding region
      of both types of genes could conceivably have a peculiar DNA or chromatin
      structure used as preferred landing sites by transposable elements.

PMID- 16453447
TI  - The amino acid sequence of chicken and muscle desmin provides a common structural
      model for intermediate filament proteins.
AB  - [This corrects the article on p. 1649 in vol. 1.].

PMID- 16453446
TI  - An improved in situ hybridization method for the detection of cellular RNAs in
      Drosophila tissue sections and its application for localizing transcripts of the
      homeotic Antennapedia gene complex.
AB  - An improved method for the detection of cellular RNAs in tissue sections has been
      developed. It involves in situ hybridization of tritium-labeled cloned DNA probes
      to tissue sections and autoradiography. The method was calibrated by using a
      cloned DNA probe complementary to transcripts abundant in the midgut cells of
      Drosophila larvae. The improved method also permitted the detection of these
      transcripts in sectioned embryos where they are much less abundant. The
      sensitivity of the method can be approximated by quantifying the signal
      intensities over the hybridizing embryonic midgut cells relative to the larval
      midgut cells for which the number of transcripts has been estimated. Based on
      these calculations we estimate that the method is sensitive enough to detect 100
      complementary RNA molecules per cell after 3 days of autoradiographic exposure
      with a signal-to-noise ratio of 10. The method has been successfully applied to
      detect transcripts of the homeotic gene Antennapedia. Serial sections allow us to
      study the spatial pattern of gene expression in the course of development.

PMID- 16453445
TI  - Ligation of endogenous tRNA 3' half molecules to their corresponding 5' halves
      via 2'-phosphomonoester,3',5'-phosphodiester bonds in extracts of Chlamydomonas.
AB  - tRNA preparations from Chlamydomonas and wheat germ contain small amounts of tRNA
      5' halves and corresponding 3' halves. Incubation of cell-free extracts from the
      two sources with [gamma-P]ATP yielded 5'-P-labeled tRNA 3' halves which were
      joined to their corresponding 5' counterparts to form mature tRNA containing 2'
      phosphomonoester,3', 5'-phosphodiester bonds. tRNA 3' halves labelled with T4
      kinase were purified, sequenced and also joined to their 5' counterparts. It is
      proposed that these tRNA halves may be intermediates of the tRNA splicing
      process, and that the RNA kinase and ligase activities observed here are part of
      the tRNA splicing complex.

PMID- 16453448
TI  - The DNA sequence of the H-2K gene: evidence for gene conversion as a mechanism
      for the generation of polymorphism in histocompatibility antigens.
AB  - [This corrects the article on p. 453 in vol. 2, PMID: 11894963.].

PMID- 16453449
TI  - Removal of symmetrical sequences from the origin region of plasmid R1 reduces its
      replication efficiency.
AB  - The R1 origin region contains many symmetrical DNA sequence elements which allow
      the formation of complex secondary structures. A 218-bp in vivo deletion in a
      cloned R1 origin fragment removes most of them. As this deletion was never
      observed in plasmids containing all R1 replication functions, it was introduced
      by BglI in vitro recombination into the ;basic replicon' of R1 cloned into
      pBR322. The recombinant plasmid with the 218-bp deletion and its derivatives
      unambiguously show that the deleted symmetrical elements are not absolutely
      essential for R1 replication as was previously assumed though they seem to
      determine a more efficient origin function. Likewise, a hypothetical protein of a
      mol. wt. of 14 000 daltons, the major part of which would be encoded by the
      deleted sequences, does not seem to be of particular importance for R1-specific
      replication. This is the first report of an alteration in the origin region of an
      IncFII plasmid which affects plasmid replication without abolishing it
      completely.

PMID- 16453450
TI  - The Alu family repeat promoter has a tRNA-like bipartite structure.
AB  - The essential sequences needed for Alu repeat transcription by RNA polymerase III
      were mapped. Experimental evidence is presented showing that the Alu repeat
      promoters are organised in a bipartite structure similar to the split tRNA
      promoters as suggested by DNA sequence homology. Furthermore, by combining
      fragments from efficiently and inefficiently transcribed natural Alu repeats in
      several recombinant clones, it was possible to investigate the regions
      responsible for their differences. It is clear that, apart from the short
      stretches of homology with the tRNA consensus sequence, there is very little
      constraint in the promoter sequences. However, our studies indicate that some
      influence on the efficiency of transcription may be exerted by regions outside
      the accepted promoter components.

PMID- 16453451
TI  - Heat-shock proteins are associated with hnRNA in Drosophila melanogaster tissue
      culture cells.
AB  - Ribonucleoprotein complexes of Drosophila melanogaster Kc tissue culture cells
      grown at 24 degrees C or heat-shocked at 37 degrees C were cross-linked in vivo
      by u.v. irradiation. Cross-linked heterogeneous nuclear ribonucleoprotein (hnRNP)
      complexes were fractionated by oligo(dT)-cellulose chromatography and CsCI
      density centrifugation. The hnRNP complexes of both 24 degrees C and 37 degrees C
      culture cells possess buoyant densities in CsCI between varrho = 1.38 g/cm and
      1.43 g/cm. The S-labelled proteins bound to the hnRNA of 37 degrees C culture
      cells correspond in mol. wt. to the so-called heat-shock proteins of 70 K, 68 K,
      27 K, 26 K, 23 K and 22 K. The 70 K and 68 K proteins are also present in hnRNP
      complexes of 24 degrees C culture cells. In addition, several other Drosophila
      hnRNPs of 140 K, 56 K, 45 K, 43 K, 38 K, 37 K and 34 K, whose synthesis is
      strongly repressed under heat-shock conditions, could be identified. The results
      demonstrate that the so-called heat-shock proteins possess a function as RNPs.

PMID- 16453452
TI  - The mechanism of inducer exclusion. Direct interaction between purified III of
      the phosphoenolpyruvate:sugar phosphotransferase system and the lactose carrier
      of Escherichia coli.
AB  - A hypothesis for the regulation of some sugar transport systems by the bacterial
      phosphoenolpyruvate:sugar transport system postulates an interaction between III
      of this system and the carrier whose activity is regulated. We have studied this
      interaction in more detail, employing one of these transport systems, the lactose
      carrier of Escherichia coli. Purified III of the phosphotransferase system
      interacted directly with the lactose carrier. The binding of III to lactose
      carrier required the presence of the non-phosphorylated form of III and
      substrates of the carrier and exhibited a stoichiometry of 1.2+/- 0.2 mol III/mol
      lactose carrier. The K(d) of lactose carrier for III was 10 +/- 5 microM. III is
      apparently unable to interact with a mutant lactose carrier which still binds but
      does not transport galactosides. The binding of III to the lactose carrier
      results in a 3.5-fold increase in the apparent affinity of galactosides for the
      carrier. Significantly, the binding of III to the lactose carrier results in an
      inhibition of galactoside translocation both in membrane vesicles and liposomes
      reconstituted with the purified lactose carrier. This inhibition may thus be the
      basis for the well-documented phenomenon of inducer exclusion.

PMID- 16453453
TI  - Widely differing degrees of sequence conservation of the two types of rDNA
      insertion within the melanogaster species sub-group of Drosophila.
AB  - We have examined the distribution of sequences homologous to the type I and type
      II rDNA insertions of Drosophila melanogaster in its sibling species. Each of the
      six species we have examined has sequences homologous to the type I insertion,
      which have undergone extensive divergence by the criterion of their EcoRI, BstI
      and HindIII restriction patterns. We have isolated cosmid clones containing type
      I sequences from D. simulans and D. mauritiana, the two species most closely
      related to D. melanogaster. Southern hybridisation analysis of these clones
      indicates that, as in D. melanogaster, the type I sequences can exist
      independently of rDNA and can also dissociate to give sub-components homologous
      to the right hand segment of the D. melanogaster type I insertion. The type II
      sequences, on the other hand are present in five out of the six species, but
      their restriction endonuclease cleavage profile is highly conserved. The
      differences in the degree of conservation of the two types of insertion sequence
      are discussed.

PMID- 16453455
TI  - Structural organization of the rat gene for the arginine vasopressin-neurophysin
      precursor.
AB  - [This corrects the article on p. 763 in vol. 2, PMID: 6315416.].

PMID- 16453454
TI  - Structural homology between different archaebacterial DNA-dependent RNA
      polymerases analyzed by immunological comparison of their components.
AB  - The archaebacterial DNA-dependent RNA polymerases have a complex structure
      containing eight or more components. Immunochemical analysis shows an extensive
      homology between the components of the enzymes of nine different species. Two
      enzyme subtypes can be distinguished: that of the thermoacidophilic and/or sulfur
      metabolizing archaebacteria with the composition BACDEFGHIJ and that of the
      methanogenic plus halophilic archaebacteria with the composition ABB'C(D)....
      Components B and B' of the latter subtype probably evolved by the division of the
      large component B of the BACD... type enzyme. The existence of the two subtypes
      corroborates the division of the archaebacteria into two phylogenetic main
      branches.

PMID- 16453456
TI  - Molecular analysis of large transposable elements carrying the white locus of
      Drosophila melanogaster.
AB  - A large transposable element (TE) comprising the white-apricot and roughest genes
      has been found to transpose to well over a hundred sites scattered over the
      Drosophila genome. We report the cloning of the essential parts of several TEs.
      TE98 and TE28 sequences were cloned by ;walking' along the chromosome from the
      previously cloned heatshock genes. The ends of the TEs are characterized by
      dispersed repetitive elements belonging to the foldback (FB) family. FB elements
      are also associated with two independently isolated transposable elements
      originating from the white locus, Tp w-1 and Tp w. The strong correlation between
      FB elements and large composite transposons suggests that a pair of these
      elements can mobilize large intermediary DNA segments. One particular FB family
      member, FB-NOF, is associated with TE28, the white-crimson (w) mutant, the w
      derived Tp w-1 and probably also with Tp w. A unique sequence located close to
      the white end of TE28 was used to clone the borders of TE77 and the surrounding
      sequences in the bithorax region, indicating that the TE can be used as a probe
      for gene isolation. Some evolutionary implications of the large composite
      transposons are discussed.

PMID- 16453457
TI  - Isolation of a laminin-binding protein from muscle cell membranes.
AB  - Skeletal muscle myofibers are each ensheathed by a continuous basal lamina
      consisting predominantly of type IV collagen, laminin and heparan sulfate
      proteoglycan. In order to identify laminin-binding components in the muscle cell
      surface, plasma membranes from mouse thigh muscle and from rat L6 myoblasts were
      separated by polyacrylamide gel electrophoresis and transferred to nitrocellulose
      paper by electroblotting. Incubation of the transferred samples with I-labelled
      laminin revealed a prominent band of approximate mol. wt. 68 000. A protein of
      this mol. wt. was isolated by affinity chromatography of muscle cell plasma
      membranes on laminin-Sepharose. The hydrophobic protein has an apparent mol. wt.
      of 68 000 and has a high content of serine, glycine and acidic amino acids. After
      detergent solubilization the purified protein binds to laminin-coated Sepharose
      beads at a higher rate than to beads coated with either fibronectin or collagen
      types I and IV. The interaction of the protein, called LB 68, with laminin was
      also studied after incorporation into synthetic lecithin vesicles. While
      detergent-solubilized LB 68 bound to I-labeled laminin only at lower than
      physiological ionic strength, liposome-incorporated LB 68 bound to laminin in the
      absence of detergents under physiological conditions. We propose that this
      protein is involved in the interaction of myoblasts with laminin substrates and
      thus may participate in the anchorage of the basal lamina in the plasmalemma of
      myotubes.

PMID- 16453458
TI  - Interaction of cytochrome c and its precursor apocytochrome c with various
      phospholipids.
AB  - The effects of cytochrome c and apocytochrome c on the structural properties of
      various membrane phospholipids in model systems were compared by binding,
      calorimetric, permeability, P n.m.r. and freeze-fracture experiments. Both
      cytochrome c and apocytochrome c experience strong interactions only with
      negatively charged phospholipids; apocytochrome c interacted more strongly than
      cytochrome c. These interactions are primarily electrostatic but also have a
      hydrophobic character. Cytochrome c as well as apocytochrome c induces changes in
      the structure of cardiolipin liposomes as is shown by P n.m.r. and freeze
      fracture electron microscopy. Cytochrome c does not affect the bilayer structure
      of phosphatidylserine. In contrast, interaction of apocytochrome c with this
      phospholipid results in changes of the P n.m.r. bilayer spectrum of the liposomes
      and also particles are observed at the fracture faces. The results are discussed
      in relation to the import of the protein into the mitochondrion.

PMID- 16453459
TI  - Microdissection and cloning of the white locus and the 3B1-3C2 region of the
      Drosophila X chromosome.
AB  - Fragments from the 3B-3C region of the Drosophila X chromosomes were
      microdissected from salivary gland squashes and their DNA was cloned by the
      method developed by Scalenghe et al. (1981). These clones were used as starting
      points for a chromosome walk which covers 200 kb including bands 3B2 to 3C2. A
      number of deletion breakpoints were mapped on the cloned DNA allowing the
      localisation of several genes in the 3B region. The white locus in particular was
      isolated by microcloning the w insertion site. Two transcripts, of 2 and 2.4 kb,
      respectively, arise from the white region and its vicinity.

PMID- 16453460
TI  - Monoclonal antibody characterisation of slime sheath: the extracellular matrix of
      Dictyostelium discoideum.
AB  - Proteins can be extracted from the slime sheath of Dictyostelium discoideum slugs
      by denaturing agents. A subset of these proteins is also released by cellulase
      digestion of the sheath, implying that protein-protein and protein-cellulose
      interactions are involved in sheath protein retention. It seems probable that the
      cellulose-associated sheath proteins are also associated with the cellulose of
      mature stalk cells. Monoclonal antibodies directed against sheath demonstrate
      extensive sharing of antigenic determinants between sheath proteins and a limited
      degree of antigenic sharing between sheath and slug cell proteins. All of the
      proteins recognised by these monoclonal antibodies are developmentally regulated.
      These results are discussed in terms of the structure of the sheath and its
      possible role(s) in D. discoideum development.

PMID- 16453461
TI  - Cloning of the symbiotic region of Rhizobium leguminosarum: the nodulation genes
      are between the nitrogenase genes and a nifA-like gene.
AB  - The region of the Rhizobium leguminosarum plasmid pRL1JI involved in nodulation
      and nitrogen fixation has been cloned on a series of four overlapping cosmid
      clones. These clones represent 60 kb of pRL1JI DNA on which a series of Tn5
      induced fix and nod alleles have been identified, with the two most distant
      alleles being separated by 45 kb of DNA. The mutant alleles fell into three
      groups, two clusters of fix alleles separated by one cluster of nod alleles.
      Within one group of fix alleles, DNA homologous to the nifA gene of Klebsiella
      pneumoniae has been identified, whereas the pRL1JI DNA homologous to the K.
      pneumoniae nitrogenase genes is present within the other group of fix alleles.

PMID- 16453462
TI  - Nodule-specific host proteins in effective and ineffective root nodules of Pisum
      sativum.
AB  - Nodule-specific root proteins - so called nodulins - were identified in root
      nodules of pea plants by an immunological assay. Nodulin patterns were examined
      at different stages of nodule development. About 30 nodulins were detectable
      during development. Some were preferentially synthesized before nitrogen fixation
      started, whereas the majority were synthesized concomitantly with leghaemoglobin.
      Some of the nodulins were located within the peribacteroid membrane. Ineffective
      Rhizobium strains (a natural nodfix and a pop fix) appeared to be useful in
      studying the expression of nodulin genes. Synthesis of some nodulins was
      repressed in ineffective root nodules, indicating that nodulins are essential for
      the establishment of nitrogen fixation. In both types of ineffective root
      nodules, leghaemoglobin synthesis was not completely repressed. Low amounts of
      leghaemoglobin were always detected in young ineffective root nodules whereas in
      old nodules no leghaemoglobin was present.

PMID- 16453463
TI  - Genes and transcripts for the polypeptides of the cytochrome b6/f complex from
      spinach thylakoid membranes.
AB  - Cytochrome b6/f complex was prepared from washed thylakoid membranes by a
      procedure involving detergent treatment and centrifugation in sucrose gradients.
      The complex is composed of at least four polypeptide species, cytochrome f which
      occurs in two variant forms (mol. wt. 34/33 kd), cytochrome b6 (23 kd), the high
      potential Rieske iron-sulfur protein (19 kd) and a fourth subunit (17 kd) of
      unknown function. Transcripts for the cytochromes f, b6 and subunit 4 were found
      in plastid RNA, those for the Rieske iron-sulfur protein in cytosolic poly(A)
      RNA. Transcripts for cytochrome b6 and subunit 4 are translated in rabbit
      reticulocyte lysates into products of correct length. The Rieske iron-sulfur
      protein and the cytochrome f apoprotein appear to be made as precursors with
      excess sequences of 7 and 4 kd, respectively. Cytochrome f, cytochrome b6 and
      subunit 4 are encoded by uninterrupted plastid genes that are located in the
      large single-copy region of the circular DNA molecule. Each of these genes is
      present once per chromosome. Their location and direction of transcription have
      been determined by hybrid-selection mapping and by cell-free
      transcription/translation of various recombinant DNAs. The genes for cytochrome
      b6 and for subunit 4 lie near each other, but do not overlap. They are
      transcribed into a single message. The gene for cytochrome f maps 15 kbp away
      from this cluster, close to the 3' end of the gene for the large subunit of
      ribulosebisphosphate carboxylase/oxygenase, and is transcribed into a separate 4
      kb long RNA. All these genes have the same polarities with respect to each other.

PMID- 16453464
TI  - Chimeric genes as dominant selectable markers in plant cells.
AB  - Opine synthases are enzymes produced in dicotyledonous plants as the result of a
      natural gene transfer phenomenon. Agrobacteria contain Ti plasmids that direct
      the transfer, stable integration and expression of a number of genes in plants,
      including the genes coding for octopine or nopaline synthase. This fact was used
      as the basis for the construction of a number of chimeric genes combining the 5'
      upstream promoter sequences and most of the untranslated leader sequence of the
      nopaline synthase (nos) gene with the coding sequence of two bacterial genes: the
      aminoglycoside phosphotransferase (APH(3')II) gene of Tn5 and the methotrexate
      insensitive dihydrofolate reductase (DHFR Mtx) of the R67 plasmid. The APH(3')II
      enzyme inactivates a number of aminoglycoside antibiotics such as kanamycin,
      neomycin and G418. Kanamycin, G418 and methotrexate are very toxic to plants. The
      chimeric NOS-APH(3')II gene, when transferred to tobacco cells using the Ti
      plasmid as a gene vector, was expressed and conferred resistance to kanamycin to
      the plant cells. Kanamycin-resistant tobacco cells were shown to contain a
      typical APH(3')II phosphorylase activity. This chimeric gene can be used as a
      potent dominant selectable marker in plants. Similar results were also obtained
      with a NOS-DHFR Mtx gene. Our results demonstrate that foreign genes are not only
      transferred but are also functionally expressed when the appropriate
      constructions are made using promoters known to be active in plant cells.

PMID- 16453465
TI  - Synthesis and processing of thionin precursors in developing endosperm from
      barley (Hordeum vulgare L.).
AB  - Thionin is a lysine-rich polypeptide (mol. wt. 5000) which is synthesized in
      developing barley endosperm from 8 days to 30 days after anthesis. Two thionin
      precursors (THP1 and THP2) have been identified using monospecific antibodies (A
      TH) prepared against the mature protein. THP1, which is the only polypeptide
      recognized in vitro by A-TH, is encoded by a 7.5S mRNA obtained from membrane
      bound polysomes, and its alkylated derivative has an apparent mol. wt. of 17 800.
      THP2, which is selected together with mature thionin by A-TH among labelled
      proteins in vivo, differs from THP1 in apparent mol. wt. (17 400 alkylated) and
      in electrophoretic mobility at pH 3.2. Both THP1 and THP2 are competed out of the
      antigen-antibody complex by purified thionin. The conversion of THP2 into
      thionin, which has been demonstrated in a pulse-chase experiment in vivo, is a
      post-translational process. As it has not been possible to detect THP1 in vivo it
      is assumed that it is converted co-translationally into THP2. Final deposition of
      thionin as an extrinsic membrane protein, possibly associated with the
      endoplasmic reticulum, has been tentatively established on the basis of
      subcellular fractionation experiments.

PMID- 16453466
TI  - The outer membrane of yeast mitochondria: isolation of outside-out sealed
      vesicles.
AB  - The yeast mitochondrial outer membrane was isolated and 10 of its major
      polypeptides were identified (mol. wts. 109, 70, 57, 45, 45, 42, 33, 29, 25 and
      14 kd). The membrane has no major polypeptide in common with either mitochondrial
      inner membrane or rough microsomes. Protease treatment and immunochemical
      techniques showed that virtually all of the isolated outer membrane vesicles are
      sealed and display the same surface orientation as in the intact mitochondrion.

PMID- 16453467
TI  - Yeast mitochondrial outer membrane specifically binds cytoplasmically-synthesized
      precursors of mitochondrial proteins.
AB  - The precursor of cytochrome b(2) (a cytoplasmically-synthesized mitochondrial
      protein) binds to isolated mitochondria or to isolated outer membrane vesicles.
      Binding does not require an energized inner membrane, is diminished by trypsin
      treatment of the membranes and is not observed with the partially processed
      (intermediate) form of the cytochrome b(2) precursor or with non-mitochondrial
      proteins. Upon energization of the mitochondria, the bound precursor is imported
      and cleaved to the mature form. Similar results were obtained with the precursor
      of citrate synthase. This receptor-like binding activity was present in isolated
      outer, but not inner membrane. It was solubilized from outer membrane with non
      ionic detergent and reconstituted into liposomes.

PMID- 16453469
TI  - Amino acid sequence of seminalplasmin, an antimicrobial protein from bull semen.
AB  - Analytical ultracentrifugation of highly purified seminalplasmin revealed a
      molecular mass of 6300. Amino acid analysis of the protein preparation indicated
      the absence of sulfur-containing amino acids cysteine and methionine. The amino
      acid sequence of seminalplasmin was determined by manual Edman degradation of
      peptides obtained by proteolytic enzymes trypsin, chymotrypsin and thermolysin:
      NH(2)-Ser Asp Glu Lys Ala Ser Pro Asp Lys His His Arg Phe Ser Leu Ser Arg Tyr Ala
      Lys Leu Ala Asn Arg Leu Ser Lys Trp Ile Gly Asn Arg Gly Asn Arg Leu Ala Asn Pro
      Lys Leu Leu Glu Thr Phe Lys Ser Val-COOH. The number of amino acids according to
      the sequence were 48, the molecular mass 6385. As predicted from the sequence,
      seminalplasmin very likely contains two alpha-helical domains in which residues 8
      17 and 40-48 are involved. No evidence for the existence of beta-sheet structures
      was obtained. Treatment of seminalplasmin with the above proteases as well as
      with amino peptidase M and carboxypeptidase Y completely eliminated biological
      activity.

PMID- 16453468
TI  - In vivo sulfation of the contact site A glycoprotein of Dictyostelium discoideum.
AB  - During the development of Dictyostelium discoideum from the growth phase to the
      aggregation stage, a glycoprotein with an apparent mol. wt. of 80 kd is known to
      be expressed on the cell surface. This glycoprotein, referred to as contact site
      A, has been implicated in the formation of species-specific, EDTA-stable contacts
      of aggregating cells. When developing cells were labeled in vivo with [S]sulfate,
      the 80-kd glycoprotein was found to be the most prominently sulfated protein.
      Another strongly sulfated protein had an apparent mol. wt. of 130 kd and was,
      like the 80-kd glycoprotein, developmentally regulated and associated with the
      particulate fraction of the cells. The [S]sulfate incorporated into the 80-kd and
      130-kd proteins was not present as tyrosine-O-sulfate, a modified amino acid
      found in many proteins of mammalian cells. D. discoideum cells incubated with
      [S]sulfate in the presence of tunicamycin, an inhibitor of N-glycosylation,
      produced a 66-kd protein that reacted with monoclonal antibodies raised against
      the 80-kd glycoprotein, but no longer contained [S]sulfate. These results suggest
      that sulfation of the 80-kd glycoprotein occurred on carbohydrate residues. The
      possible importance of sulfation for a role of the 80-kd glycoprotein in cell
      adhesion is discussed.

PMID- 16453470
TI  - The chromosomal arrangement of six soybean leghemoglobin genes.
AB  - Clones containing six leghemoglobin (Lb) genes have been isolated from two
      genomic libraries of soybean. They encompass two independent DNA regions: a 40-kb
      region containing four genes in the order 5' Lba-Lbc(1)-[unk]Lb-Lbc(3) 3' with
      the same transcriptional polarity, and another 40-kb region containing two genes
      in the order 5' Lbc(4)-Lbc(2) 3' with the same polarity. The order in which the
      Lb genes are arranged in the soybean genome imply that they are activated in the
      opposite order to which they are arranged on the chromosome. There is a close
      similarity between corresponding DNA regions outside the Lb genes in the two
      clusters. Thus, a moderately repetitive DNA element is present in corresponding
      positions in each cluster. In addition, at least two different non-Lb genes are
      linked to each Lb gene cluster in corresponding positions. These genes are
      apparently regulated in a way which differs from that of the Lb genes. The
      existence of two very similar Lb gene clusters in soybean suggest that soybean
      may have evolved from an ancestral form by genome duplication.

PMID- 16453471
TI  - The Balbiani ring 2 gene in Chironomus tentans is built from two types of
      tandemly arranged major repeat units with a common evolutionary origin.
AB  - The internal structure of the 37 kb long Balbiani ring 2 (BR 2) gene in
      Chironomus tentans has been studied by analysis of a collection of cloned cDNA
      sequences and in genomic Southern blot analysis with the cDNA sequences used as
      probes. The BR 2 gene contains two types of tandemly arranged major repeat units
      200 bp long, represented in our study by the pCt 7 and the pCt 63 cDNA inserts.
      The pCt 7 major repeat units are arranged in one or possibly a few blocks and
      cover 10 kb of the gene; the pCt 63 units form one uninterrupted block, 22 kb in
      length. Genomic Southern blot hybridizations revealed a number of sequence
      variants of the pCt 7 major repeat unit. In contrast, the 100 copies of the pCt
      63 major repeat unit seem to be almost identical. The pCt 7 major repeat unit,
      180 bp in length, is organized in the same way as the previously described 215 bp
      long pCt 63 major repeat, i.e., it contains a repetitive and a non-repetitive
      part. Moreover, the two major repeat units show a high degree of sequence
      homology, indicating that the pCt 7 and pCt 63 sequence blocks within the Br 2
      gene have evolved through stepwise amplification from a common ancestral
      sequence.

PMID- 16453472
TI  - Identification of sequences involved in the polyadenylation of higher plant
      nuclear transcripts using Agrobacterium T-DNA genes as models.
AB  - [This corrects the article on p. 419 in vol. 2, PMID: 11894958.].

PMID- 16453473
TI  - Partial rescue of dorsal, a maternal effect mutation affecting the dorso-ventral
      pattern of the Drosophila embryo, by the injection of wild-type cytoplasm.
AB  - Mutant alleles at the maternal effect locus dorsal cause a dorsalization of the
      Drosophila embryo. In extreme mutants, the embryos develop exclusively structures
      which derive from the dorsal-most region in normal eggs, in less strong
      phenotypes in addition to dorsal structures, structures normally derived from a
      dorso-lateral to lateral egg region are formed. Injection of cytoplasm from wild
      type embryos into mutant embryos partially restores the dorso-ventral pattern in
      that injected embryos develop additional structures never formed in uninjected
      control embryos or embryos injected with mutant cytoplasm. The phenotype of
      injected embryos resembles that of weaker alleles at the dorsal locus indicating
      that the wild-type cytoplasm partially rescues the mutant phenotype. The response
      of the mutant embryos is restricted to the site of injection and occurs only when
      cytoplasm is injected into the ventral and not into the dorsal side of mutant
      embryos. The rescuing activity appears to be equally distributed in cleavage
      stage wild-type embryos, whereas, in syncytial blastoderm embryos, cytoplasm from
      the ventral side is about twice as effective as that taken from the dorsal side.

PMID- 16453474
TI  - Molecular cloning of microdissected lampbrush loop DNA sequences of Drosophila
      hydei.
AB  - We microdissected a Y chromosomal lampbrush loop pair from primary spermatocyte
      nuclei of Drosophila hydei and cloned the DNA directly at the microscale. Four of
      the 12 recombinant DNA clones recovered display in situ hybridization to mitotic
      metaphase Y chromosomes, preferentially in the chromosomal region identified as
      the origin of the lampbrush loop pair. All clones, however, also hybridize to
      autosomal and X chromosomal loci in polytene chromosomes. Y chromosomal DNA
      sequences of D. hydei again prove to be members of different families of repeated
      sequences distributed throughout the genome. These microcloning experiments,
      which were carried out under very unfavourable experimental conditions (low DNA
      content of the lampbrush loops in the presence of large amounts of RNA) prove
      that almost any chromosomal structure detected by light microscopy is directly
      accessible to molecular cloning experiments by micromethods.

PMID- 16453475
TI  - A transformation system for the hypotrichous ciliate Stylonychia mytilus.
AB  - We describe a transformation system for the ciliate Stylonychia mytilus. The
      neomycin resistance gene from Escherichia coli transposon Tn5, which codes for
      the enzyme phosphotransferase and confers resistance to the antibiotic G 418, was
      ligated into macronuclear ;gene-size' DNA molecules. Using this recombinant DNA
      for transformation experiments we show that the gene is replicated and expressed
      in transformed cells.

PMID- 16453477
TI  - Coding and 3' non-coding nucleotide sequence of chalcone synthase mRNA and
      assignment of amino acid sequence of the enzyme.
AB  - The nucleotide sequence of an almost complete cDNA copy of chalcone synthase mRNA
      from cultured parsley cells (Petroselinum hortense) has been determined. The cDNA
      copy comprised the complete coding sequence for chalcone synthase, a short A-rich
      stretch of the 5' non-coding region and the complete 3' non-coding region
      including a poly(A) tail. The amino acid sequence deduced from the nucleotide
      sequence of the cDNA is consistent with a partial N-terminal sequence analysis,
      the total amino acid composition, the cyanogen bromide cleavage pattern, and the
      apparent mol. wt. of the subunit of the purified enzyme.

PMID- 16453476
TI  - The alpha-subunit of the maize F(1)-ATPase is synthesised in the mitochondrion.
AB  - The F(1)-ATPase complex has been purified from maize (Zea mays L.) mitochondria
      and shown to consist of five subunits with mol. wts. of 58 000 (alpha), 56 000
      (beta), 35 000 (gamma), 22 000 (delta) and 8000 (epsilon). The alpha-subunit co
      migrates on one- and two- dimensional isoelectric focussing-SDS polyacrylamide
      gels with the major polypeptide synthesised by isolated mitochondria. One
      dimensional proteolytic peptide mapping and immunoprecipitation confirms that the
      alpha-subunit is a mitochondrial translation product and therefore presumably
      encoded in mitochondrial DNA. This contrasts with the situation in animal and
      fungal cells where all five subunits of the F(1)-ATPase are encoded by the
      nuclear genome and synthesised on cytosolic ribosomes.

PMID- 16453478
TI  - Point mutation in the 30-K open reading frame of TMV implicated in temperature
      sensitive assembly and local lesion spreading of mutant Ni 2519.
AB  - Tobacco mosaic virus mutant Ni 2519 forms local lesions on tobacco cultivars
      carrying the N gene which, unlike wild-type lesions, do not enlarge at elevated
      temperature. This may reflect temperature sensitivity of a viral gene product
      required for cell to cell spreading of infectivity. Ni 2519 also carries an
      unselected cis-dominant lesion in viral assembly. Peptide mapping of in vitro
      translation products of Ni 2519 RNA reveals at least one, and possibly two
      changes in p30 and p19, two products of the 30-K open reading frame, compared
      with its parental strain A14. An A to G transition at position 5332 in Ni 2519
      RNA accounts for the altered mobility of the major variable peptide. The
      corresponding A14 peptide itself differs from the wild-type due to another A to G
      transition at residue 5329. These residues are close to the viral assembly
      origin. A revertant virus population which could assemble at the restrictive
      temperature regained the wild-type sequence in place of the point mutation
      specific to Ni 2519 at position 5332, and formed wild-type local lesions as
      efficiently as the parental strain. This result implicates mutation of residue
      5332 in the temperature sensitivity of viral assembly (by altering the structure
      of the RNA close to the assembly origin) and/or local lesion spreading (via a
      radical Arg to Gly substitution in p30 or its derivatives). The mutation occurs
      in a position where the predicted amino acid sequence shows homology with a group
      of proteins encoded by yeast mitochondrial introns.

PMID- 16453479
TI  - An extended secondary structure model for the TMV assembly origin, and its
      correlation with protection studies and an assembly defective mutant.
AB  - Recognition of the unique internal assembly origin on tobacco mosaic virus (TMV)
      RNA by the disk aggregate of the viral coat protein probably involves an extended
      region of the RNA (larger than that coated by a single disk) folded into a
      specific conformation. A secondary structure model is proposed for the RNA
      preferentially coated by limiting amounts of coat protein disks on the basis of
      partial nuclease digestion data. Part of this sequence can form three
      symmetrically spaced hairpins with marginally stable base paired sequences at the
      tips of the stems. The pattern of progressive protection of the RNA from nuclease
      attack during assembly suggests that these three hairpins are successively coated
      by the first three disks to add. The spacing of these hairpins is identical to
      that of three hairpins in the pseudo assembly origin (part of the coat protein
      gene homologous to the assembly origin). In Ni 2519, a TMV mutant whose assembly
      is defective at high temperature because it can no longer discriminate between
      the true and pseudo assembly origins, a point mutation has occurred near the tip
      of the third metastably base paired stem of the true assembly origin which would
      disrupt its structure and alter one copy of a repeated heptanucleotide. This
      suggests an important role for the ordered and cooperative recognition of
      successive loops in determining the specificity of assembly.

PMID- 16453481
TI  - The genes coding for the muscle contractile proteins, myosin heavy chain, myosin
      light chain 2, and skeletal muscle actin are located on three different
      chromosomes.
AB  - [This corrects the article on p. 1299 in vol. 1.].

PMID- 16453480
TI  - On the presence of a heme-binding domain homologous to cytochrome b(5) in
      Neurospora crassa assimilatory nitrate reductase.
AB  - Assimilatory nitrate reductase has been purified with 55% recovery from a
      Neurospora crassa nmr-1 nit-6 mutant, using a modification of a published
      procedure. It possesses one heme per 240 000 g, and subunits of mol. wt. 68 000.
      Upon digestion with chymotrypsin, a heme-binding domain was isolated by gel
      filtration; its visible spectrum was highly similar to that of cytochrome b(5).
      On SDS gels, the fraction showed two heme-containing bands of 10 000 and 12 5000
      daltons; their amino acid composition was not very different, suggesting that
      they originated from the same region of the polypeptide chain. After S
      carboxymethylation, the mixture of bands was submitted to cyanogen bromide
      cleavage, and the fragments were separated by h.p.l.c. The two largest fragments
      yielded an identical sequence upon automated degradation. This sequence (39
      residues with some gaps) could be easily aligned with that of cytochrome b(5)
      starting close to the N terminus. These results are discussed in terms of the
      possible quaternary structure of N. crassa nitrate reductase, whose heme-binding
      domain proves to be another member of the family of b(5)-like cytochromes.

PMID- 16453482
TI  - Ti plasmid vector for the introduction of DNA into plant cells without alteration
      of their normal regeneration capacity.
AB  - A Ti plasmid mutant was constructed in which all the on-cogenic functions of the
      T-DNA have been deleted and replaced by pBR322. This Ti plasmid, pGV3850, still
      mediates efficient transfer and stabilization of its truncated T-DNA into
      infected plant cells. Moreover, integration and expression of this minimal T-DNA
      in plant cells does not interfere with normal plant cell differentiation. A DNA
      fragment cloned in a pBR vector can be inserted in the pGV3850 T-region upon a
      single recombination event through the pBR322 region of pGV3850 producing a co
      integrate useful for the transformation of plant cells. Based upon these
      properties, pGV3850 is proposed as an extremely versatile vector for the
      introduction of any DNA of interest into plant cells.

PMID- 16453483
TI  - Genetic analysis of transfer and stabilization of Agrobacterium DNA in plant
      cells.
AB  - In an attempt to elucidate the transfer and integration mechanism of
      Agrobacterium DNA upon crown gall induction, we translocated a borderless T-DNA
      to different sites of the C58 Ti plasmid. As a result of the physical linkage of
      the T-DNA onc genes with other Ti plasmid functions, the concerned strain
      retained tumor-inducing capacity. However, when the borderless T-DNA is separated
      on an independent replicon while all other pTi functions are provided in trans,
      the strain can no longer induce tumors on plants. We provide evidence that the
      right T-DNA border region harbors one or more in cis active functions essential
      in the transfer and/or stabilization of the T-DNA into plant cells. The strains
      used in these experiments allowed us to conclude that some function(s) of the Ti
      plasmid can induce plant cell proliferations independently of the T-DNA
      transformation event. The results described here indicate that other Ti plasmid
      sequences than solely the T-region can be transferred to plant cells.

PMID- 16453484
TI  - Cytochrome oxidase subunit II gene in mitochondria of Oenothera has no intron.
AB  - The cytochrome oxidase subunit II gene has been localized in the mitochondrial
      genome of Oenothera berteriana and the nucleotide sequence has been determined.
      The coding sequence contains 777 bp and, unlike the corresponding gene in Zea
      mays, is not interrupted by an intron. No TGA codon is found within the open
      reading frame. The codon CGG, as in the maize gene, is used in place of
      tryptophan codons of corresponding genes in other organisms. At position 742 in
      the Oenothera sequence the TGG of maize is changed into a CGG codon, where Trp is
      conserved as the amino acid in other organisms. Homologous sequences occur more
      than once in the mitochondrial genome as several mitochondrial DNA species
      hybridize with DNA probes of the cytochrome oxidase subunit II gene.

PMID- 16453485
TI  - Molecular cloning of the avian acute transforming retrovirus MH2 reveals a novel
      cell-derived sequence (v-mil) in addition to the myc oncogene.
AB  - Mill-Hill-2 virus (MH2) proviral DNA was cloned from a transformed non-producer
      cell culture (MH2QB2) through insertion of randomly cut high mol. wt. cellular
      DNA in the lambdoid vector L47.1. Restriction analysis of a suitable recombinant
      phage by Southern DNA blotting and hybridization with different probes allowed us
      to characterize the genetic organization of the provirus and to identify a novel
      MH2-specific sequence of at least 1.1kbp. Such a sequence, for which we propose
      the name v-mil, from MilI-Hill-2 virus, is not homologous to v-myc, the
      previously described oncogene of MH2, nor to avian leukaemia virus-related
      sequences. Evidence is presented here that v-mil has a cellular counterpart (c
      mil) phylogenetically conserved in birds and mammals, including man, and
      expressed as a single RNA species at least in some tissues. MH2 virus might thus
      be regarded, like avian erythroblastosis virus or E26, as another example of
      retroviruses having recombined with more than one cellular gene.

PMID- 16453486
TI  - Localization of the genes for the two chlorophyll a-conjugated polypeptides (mol.
      wt. 51 and 44 kd) of the photosystem II reaction center on the spinach plastid
      chromosome.
AB  - A core particle of the water-oxidizing photosystem II reaction center has been
      prepared from stacked spinach thylakoid membranes by a procedure involving
      extraction with the non-ionic detergent dodecyl-beta-D-maltoside and
      centrifugation in sucrose gradients. The protein-pigment complex consists of at
      least four polypeptide species: two components with mol. wts. of 51 and 44 kd
      which are conjugated with chlorophyll a and beta-carotene, the herbicide-binding
      protein of mol. wt. 32 kd and cytochrome b 559 (11 kd). The genes for the 51-and
      44-kd polypeptides have been located on the circular 150-kbp spinach plastid
      chromosome. They were identified by hybrid-selection mapping, in vitro
      transcription-translation of recombinant DNAs and specific antisera which were
      used to characterize the translation products. The plastid chromosome carries one
      uninterrupted copy for each of these genes in its large single-copy region. The
      gene for the 51-kd protein (which probably bears the P(680) reaction center
      chlorophyll a) is located in close proximity to the gene for cytochrome b6, and
      some 70 kbp away from the gene for the ;32-kd' herbicide-binding protein of the
      reducing side of photosystem II. The gene for the 44-kd protein is situated
      halfway between these two genes adjacent to the gene for the P(700) chlorophyll a
      apoprotein of the photosystem I reaction center. Both photosystem II genes are
      transcribed into discrete RNA species in the same direction but from the opposite
      strand as the gene for the ;32-kd' protein.

PMID- 16453487
TI  - The nucleotide sequence of cowpea mosaic virus B RNA.
AB  - The complete sequence of the bottom component RNA (B RNA) of cowpea mosaic virus
      (CPMV) has been determined. Restriction enzyme fragments of double-stranded cDNA
      were cloned in M13 and the sequence of the inserts was determined by a
      combination of enzymatic and chemical sequencing techniques. Additional sequence
      information was obtained by primed synthesis on first strand cDNA. The complete
      sequence deduced is 5889 nucleotides long excluding the 3' poly(A), and contains
      an open reading frame sufficient to code for a polypeptide of mol. wt. 207 760.
      The coding region is flanked by a 5' leader sequence of 206 nucleotides and a 3'
      non-coding region of 82 residues which does not contain a polyadenylation signal.

PMID- 16453488
TI  - Nodulin-35: a subunit of specific uricase (uricase II) induced and localized in
      the uninfected cells of soybean nodules.
AB  - Nodulin-35, a protein specific to soybean root nodules, was purified under non
      denaturing conditions (DEAE-cellulose followed by Sephacryl S-200 chromatography)
      to homogeneity. The holoprotein showed uricase (EC 1.7.3.3) activity. Analytical
      ultracentrifugation under non-denaturing conditions revealed a molecule of 124
      kd, S degrees (20W) = 8.1; however, under denaturing conditions a value of 33 kd,
      S degrees (20W) = 1.9, was obtained. This indicated that nodulin-35 is the 33-kd
      subunit of a specific soybean root nodule uricase (uricase II) and that the
      enzyme contains four similar subunits. The native molecule contains 1.0 mol Cu
      per mol, has an isoelectric point of 9.0 and a pH optimum for uricase activity at
      9.5. Uricase activity found in young uninfected soybean roots is due to another
      form of enzyme (uricase I) which is of 190 kd, has maximum activity at pH 8.0 and
      does not contain any subunit corresponding in size to nodulin-35. Uricase I, also
      present in young infected roots, declines at a time when nodulin-35 appears.
      Monospecific antibodies prepared against uricase II (nodulin-35) showed no cross
      reactivity. Uricase II was localized in the uninfected cells of the nodule
      tissue. These results are consistent with the concept that a nodule-specific
      ureide metabolism takes place in peroxisomes of uninfected cells, and suggest the
      participation of uricase II in this pathway.

PMID- 16453489
TI  - Crystallisation and preliminary X-ray data of ribulose-1,5-bisphosphate
      carboxylase from spinach.
AB  - Crystals of a tertiary complex of spinach ribulose-1,5-bisphosphate
      carboxylase/oxygenase with the activators Mg and CO(2) have been grown. These
      crystals diffract strongly to 1.6 A resolution. The spacegroup is C222(1) with
      unit cell dimensions a = 158.6 A, b = 158.6 A, c = 203.4 A. Additional local
      symmetry is apparent in the pattern of absences and the intensity distribution of
      the X-ray precession photographs. The photographs have been interpreted in terms
      of a molecule (consisting of eight large and eight small subunits, L(8)S(8)) with
      222 symmetry and a molecular centre shifted 2 A in the x direction from the
      origin of the unit cell. The asymmetric unit contains half the L(8)S(8) molecule.
      The intensity distribution suggests that the molecular symmetry does not deviate
      far from 422. These crystals are compared with other crystalline forms of the
      enzyme and the implications of these results are discussed.

PMID- 16453490
TI  - Repetitive sequences and their organization on genomic clones of Zea mays.
AB  - Fourteen recombinant clones from Zea mays were studied with regard to their
      composition of unique and repetitive sequences. Southern hybridization
      experiments were used to classify restriction fragments of the clones into a
      unique, middle or highly repetitive class of reiteration frequency. All three
      classes were often found on the same genomic clone. Crosshybridization studies
      between clones showed that a given repeat might be present on several clones, and
      thus four families of highly repetitive elements were established. Heteroduplex
      analysis was used to show the arrangement and size of repeats common between
      several clones. A short interspersion pattern of unique, middle and highly
      repetitive DNA was found. The dispersed repetitive elements were 300-1300 bp in
      length. Analysis of the pattern produced by a given repeat in genomic Southern
      experiments suggests that some small dispersed repeats may also exist as part of
      a larger repeating unit elsewhere in the genome.

PMID- 16453491
TI  - Genetic identification of functions of TR-DNA transcripts in octopine crown
      galls.
AB  - Seventeen in vivo and in vitro insertion mutations in the TR-region of the
      octopine Ti plasmid B6S3 of Agrobacterium tumefaciens were constructed. They
      include mutations in each of the five TR transcripts. All mutants retained their
      oncogenic properties and induced tumors with wild-type morphology. Determination
      of opines in tumors induced by mutant Agrobacterium strains showed that
      production of mannopine and agropine are TR-linked traits. Two transcripts are
      necessary for the synthesis of mannopine and a third one for the conversion of
      mannopine into agropine. None of the mutations prevents the excretion of opines.
      In addition, none of the five transcripts is essential for transfer and
      integration of the TR-region.

PMID- 16453492
TI  - Note added in proof.

PMID- 16453495
TI  - Note added in proof.

PMID- 16453493
TI  - Regulation of gene expression in Dictyostelium discoideum cells exposed to
      immobilized carbohydrates.
AB  - When amoebae of Dictyostelium discoideum develop on gels of polyacrylamide that
      are derivatized with glucosides, they become capable of aggregation at the same
      time as cells not exposed to glucosides. However, the aggregation centers and
      streams of adherent cells formed on immobilized glucosides suddenly disintegrate.
      The cells repeatedly re-aggregate, but never form tight aggregates as they do on
      other substrata. Tight aggregates formed in the absence of glucosides disperse
      after their transfer to glucoside gels, and the cells undergo aggregation
      disaggregation cycles. The formation of tight aggregates is correlated with the
      expression of specific post-aggregative poly(A) RNAs. These RNAs are not
      expressed in cells developing on glucoside gels, and the dispersal of tight
      aggregates on such gels is accompanied by the almost complete loss of these RNAs.
      A developmentally regulated membrane glycoprotein called contact site A, which is
      a marker of aggregation-competent cells, is normally expressed on glucoside gels.
      Cyclic AMP is also produced, indicating that the strong increase of adenylate
      cyclase activity during the preaggregation phase is not affected. In conclusion,
      cell contact with immobilized glucosides specifically inhibits postaggregative
      gene expression and arrests development at the aggregation stage.

PMID- 16453494
TI  - Evidence that positional information is used to establish the prestalk-prespore
      pattern in Dictyostelium discoideum aggregates.
AB  - Two contrasting mechanisms have been proposed for the establishment of the
      prestalk-prespore pattern in the multicellular aggregate of the simple eukaryote
      Dictyostelium discoideum. One involves intermingled, non-position-dependent cell
      differentiation followed by sorting out which produces the pattern of prestalk
      cells in the anterior region and prespore cells posteriorly. The second mechanism
      involves patterning according to the position of cells within the aggregate, in
      which case intermingled cell types are not expected. Here we use a monoclonal
      antibody (MUD1), recognising a prespore cell surface antigen, to study the
      initial appearance of prespore cells in aggregates. Quantitative studies were
      made with a flow cytometer and frozen sections were used to localise the cells
      expressing the prespore antigen. This antigen first appeared at the onset of tip
      formation in the centre of aggregates in a position-dependent fashion. The
      prespore antigen was not detected in the tip region or in streams of cells
      entering the aggregate. We re-examined the evidence on which the non-position
      dependent differentiation model is based. Our results support the positional
      model for pattern formation.

PMID- 16453497
TI  - Xenopus laevis U2 snRNA genes: tandemly repeated transcription units sharing 5'
      and 3' flanking homology with other RNA polymerase II transcribed genes.
AB  - [This corrects the article on p. 1883 in vol. 2.].

PMID- 16453496
TI  - cDNA clones for the ecdysone-inducible polypeptide (EIP) mRNAs of Drosophila Kc
      cells.
AB  - The ecdysone-inducible polypeptides (EIPs) 28, 29 and 40 were identified
      previously as polypeptides whose synthesis is stimulated early in the ecdysone
      response of Drosophila Kc cells. We have now shown, using two-dimensional gels,
      that each of these EIPs consists of three species differing in pI, and all
      stimulated by ecdysone. Translations and hybrid-arrested translations indicated
      that the poly(A) EIP mRNAs increase 10-fold in abundance during the first 4 h of
      ecdysone treatment. By a differential screen of a cDNA library we have identified
      cDNA clones corresponding to all three EIPs. Two kinds of clones were isolated:
      one hybridizes to the EIP 40 mRNA(s); the second hybridizes to the mRNA(s)
      encoding all the EIPs 28 and 29. The EIP 28/29 and EIP 40 loci detected by these
      clones are each present at single sites on the polytene chromosomes and each is
      at or in the vicinity of an ecdysone-regulated puff.

PMID- 16453498
TI  - Cloning of a gene localized and expressed at the ecdysteroid regulated puff 74EF
      in salivary glands of Drosophila larvae.
AB  - The puffing cycle of salivary gland chromosomes of Drosophila larvae, which
      initiates the developmental path to pupariation, is induced by ecdysteroid
      hormone. Its action leads to prominent puffs at loci 2B5, 74EF and 75B. Fragments
      of the 74EF puff of the D. melanogaster 3L chromosome were microdissected from
      salivary gland squashes. EcoRI-digested DNA of these fragments was cloned into
      lambda phage. Clones were screened with puff stage-specific cDNA probes. Thirteen
      out of 650 clones hybridized preferentially with puff stage 4-specific cDNA. The
      prominent early puffs at 74EF and 75B are most active between puff stage 4 and 6.
      Therefore, one of the 13 lambda phages was chosen for further analysis. It was
      used to isolate 24 kb of Drosophila DNA from genomic libraries. The DNA
      hybridized in situ to locus 74F. The 74F DNA coded for a transcript, which was
      made in salivary glands, but not in fat body of third instar larvae. It
      accumulated in K(C) cells in response to ecdysteroid treatment. The
      polyadenylated transcript size was 2.7 kb as judged by Nothern blot analysis. The
      transcription start site of the 74F gene has been mapped. Sequences upstream of
      the transcription site contain several sequence elements common to other
      eucaryotic genes, including potential Z-DNA forming sequences. Also, there is
      sequence homology to upstream sequences, which have been involved in the
      regulation of transcription of the salivary gland glue protein 4 gene.

PMID- 16453499
TI  - Evidence for homologous recombination between repeated sequences containing 18S
      and 5S ribosomal RNA genes in wheat mitochondrial DNA.
AB  - Closely linked genes for 18S and 5S rRNAs have been located on four different
      cloned SalI restriction fragments of wheat (Triticum aestivum L.) mitochondrial
      DNA. Restriction analysis has revealed that in each of the cloned fragments, the
      18S and 5S rRNA genes are contained within the same basic structural unit, R,
      which is at least 4 kbp long. This unit is flanked by sequences designated u (0.8
      kbp), v (13.7 kbp), w (0.7 kbp), and y (1.4 kbp), in the orientations v-R-w, v-R
      y, u-R-w, and u-R-y in the four different SalI fragments. We conclude that 18S +
      5S rRNA genes are located at several distinct sites in the wheat mitochondrial
      genome, and suggest that reciprocal intra- and/or intermolecular recombination
      between such repeated sequences could promote extensive genomic rearrangement and
      thus contribute to the physical heterogeneity that is a hallmark of most plant
      mitochondrial DNAs.

PMID- 16453501
TI  - Note added in proof.

PMID- 16453500
TI  - RNA-dependent DNA polymerase activity in cauliflower mosaic virus-infected plant
      leaves.
AB  - Cauliflower mosaic virus (CaMV) is a plant DNA with an 8-kb circular double
      stranded genome. CaMV-specific DNA and RNA molecules present in infected Brassica
      cells share some structural features with DNAs and RNAs of retroviruses and
      hepatitis B virus. This led to the hypothesis that CaMV replication occurs via
      reverse transcription of an RNA intermediate. Here we report the first
      characterization of a new DNA polymerase activity, specific to CaMV-infected
      tissues. A subcellular fraction of infected cells shows capacity to copy poly(C)
      and the heteropolymeric regions of natural mRNAs. Chromatographic isolation of
      the poly(C)-dependent activity clearly establishes that it is distinct from the
      classical gamma-like DNA polymerases previously described in plant cells. The
      significant homology observed between defined regions of the Moloney murine
      leukemia virus (MMLV) polymerase and CaMV unassigned gene V product favours the
      idea that the reverse transcriptase-like DNA polymerase detected in infected
      cells is a virus-encoded enzyme.

PMID- 16453502
TI  - Note added in proof.

PMID- 16453503
TI  - UAG readthrough during TMV RNA translation: isolation and sequence of two tRNAs
      with suppressor activity from tobacco plants.
AB  - The hypothetical replicase or replicase subunit cistron in the 5'-proximal part
      of tobacco mosaic virus (TMV) RNA yields a major 126-K protein and a minor 183-K
      ;readthrough' protein in vivo and in vitro. Two natural suppressor tRNAs were
      purified from uninfected tobacco plants on the basis of their ability to promote
      readthrough over the corresponding UAG termination codon in vitro. In a
      reticulocyte lysate the yield of 183-K readthrough protein increases from 10% in
      the absence of added tobacco plant tRNA up to 35% in the case of pure tRNA added.
      Their amino acid acceptance and anticodon sequence (GpsiA) identifies the two
      natural suppressor tRNAs as the two normal major cytoplasmic tyrosine-specific
      tRNAs. tRNA(1) has an A:U pair at the base of the TpsiC stem and an unmodified
      G(10), whereas tRNA(2) contains a G:C pair in the corresponding location and mG
      in position 10. This is the first case that, in a higher eukaryote, the complete
      structure is known of both the natural suppressor tRNAs and the corresponding
      viral RNA on which they exert their function. The corresponding codon-anticodon
      interaction, which is not in accordance with the wobble hypothesis, and the
      possible biological significance of the readthrough phenomenon is discussed.

PMID- 16453504
TI  - T-DNA of a crown gall tumor is organized in nucleosomes.
AB  - Nucleosomes were isolated from chromatin of suspension cultured cells of
      Nicotiana tabacum var. White Burley, which were either habituated or transformed
      by Agrobacterium tumefaciens, strain T37. Chromatin repeat length in both types
      of tissue was identical and can be estimated to be 195 +/- 10 bp. Using Southern
      transfer of nucleosomal DNA and hybridization with cloned nick-translated HindIII
      fragments of pTi C58 we show that the T-DNA originating from the Ti-plasmid of A.
      tumefaciens is organized in nucleosomes within the chromatin of crown gall tumor
      cells.

PMID- 16453505
TI  - Note added in proof.

PMID- 16453506
TI  - Localization and sequence analysis of chloroplast DNA sequences of Chlamydomonas
      reinhardii that promote autonomous replication in yeast.
AB  - Four distinct chloroplast DNA segments from Chlamydomonas reinhardii of 400, 415,
      730 and 2300 bp which promote autonomous replication in yeast have been mapped on
      the chloroplast genome. Plasmids carrying these chloroplast DNA fragments are
      unstable in yeast when the cells are grown under non-selective conditions.
      Sequence analysis of three of these chloroplast ARS regions (autonomously
      replicating sequences in yeast) reveals a high AT content, numerous short direct
      and inverted repeats and the presence of at least one element in each region that
      is related to the yeast ARS consensus sequence. A/T TTTATPuTTT A/T. These three
      chloroplast regions share, in addition, two common elements of 10 and 11 bp which
      may play a role in promoting autonomous replication.

PMID- 16453508
TI  - Note added in proof.

PMID- 16453507
TI  - Note added in proof.

PMID- 16453509
TI  - Note added in proof.

PMID- 16453510
TI  - Cloning and sequencing of the preprotoxin-coding of the yeast M1 double-stranded
      RNA.
AB  - [This corrects the article on p. 107 in vol. 3, PMID: 6368221.].

PMID- 16453511
TI  - Partial characterization of the biosynthesis and integration of the Photosystem
      II reaction centers in the thylakoid membrane of Chlamydomonas reinhardtii.
AB  - Pulse-labeling of wild-type and a Photosystem II mutant strain of Chlamydomonas
      reinhardtii was carried out in the presence or absence of inhibitors of either
      cytoplasmic or chloroplast ribosomes, and their thylakoid membrane polypeptides
      were analyzed by polyacrylamide gel electrophoresis. A pulse-chase study was also
      done on the wild-type strain in the presence of anisomycin, an inhibitor of
      protein synthesis on cytoplasmic ribosomes. The following results were obtained:
      the Photosystem II reaction center is mainly composed of integral membrane
      proteins synthesized within the chloroplast. Several of the proteins of the
      Photosystem II reaction center are post-translationally modified, after they have
      been inserted in the thylakoid membrane.

PMID- 16453512
TI  - Development-dependent modification of the extracellular matrix by a sulphated
      glycoprotein in Volvox carteri.
AB  - We report the chemical characterization of the highly sulphated glycoprotein SSG
      185 from Volvox carteri. SSG 185 is a hydroxyproline-containing, extracellular
      glycoprotein. The sulphate residues are clustered within the parent saccharide
      structure of SSG 185, since on mercaptolysis all the sulphate residues are
      recovered in a small saccharide fragment containing mannose, arabinose and
      sulphate (in a molar ratio of 112). SSG 185 is a short-lived molecule, serving as
      a precursor for a high mol. wt. component of the extracellular matrix. Synthesis
      of SSG 185 is developmentally controlled. Different SSG 185 variants, with
      unknown modifications in the sulphated saccharide fragment, are synthesized at
      different developmental stages or under the influence of the sexual inducer.
      These modifications remain conserved in the aggregated state of SSG 185,
      indicating the development-dependent modification of the extracellular matrix.

PMID- 16453513
TI  - Archaebacterial heat-shock proteins.
AB  - The response to heat shock was examined in seven archaebacterial strains from the
      genus Halobacterium. Upon heat shock each strain preferentially synthesized a
      limited number of proteins which fell into three narrow mol. wt. ranges. Further
      examination of the heat-shock response in H. volcanii revealed that heat-shock
      protein (hsp) synthesis was greatest at 60 degrees C. Synthesis of hsps at this
      induction temperature was both rapid and transient. Cells recovered their normal
      protein synthesis patterns rapidly upon returning to their normal growth
      temperature following heat shock. H. volcanii cells also responded with a ;heat
      shock-like' response to salt dilution, a natural environmental stress for these
      organisms. These results indicate that the heat shock or stress response which is
      charactertistic of eukaryotic and eubacterial cells is also present among members
      of the archaebacterial genus Halobacterium.

PMID- 16453514
TI  - The preparation and characterisation of native photoreceptor units from the
      thylakoids of Rhodopseudomonas viridis.
AB  - The photosynthetic membranes of Rhodopseudomonas viridis consist of a regular
      array of structural units. Each unit is composed of a central core (thought to
      contain the reaction centre complex) surrounded by a subdivided ring of protein
      (of likely antennae function). These individual units can be dissociated from the
      membrances using a variety of detergent treatments. The absorption spectrum, used
      as a criterion of a native state, is retained. All of the seven major
      polypeptides, the four reaction centre polypeptides (cytochrome, H, M and L
      chain) as well as the three light-harvesting polypeptides (B1015-alpha, beta and
      xi) are shown to be present. Electron microscopy of the units shows a similar
      structure to the units within the membrane. surface-specific iodination of both
      membranes and units labels predominantly polypeptides H, B1015-alpha, and xi. M
      and L are weakly labelled. In addition, B1015-beta is labelled in the isolated
      units. This, with other evidence, supports an allocation of light-harvesting
      polypeptides to the outer ring. Further solubilisation of these units separates
      the reaction centre (as a native complex containing all four polypeptides) from
      the light-harvesting polypeptides. The light-harvesting polypeptides are obtained
      in a form containing all three polypeptides and bound pigment, however the peak
      at 1015 nm corresponding to native bacteriochlorophyll b is lost.

PMID- 16453515
TI  - The structure of the photoreceptor unit of Rhodopseudomonas viridis.
AB  - The thylakoid membrane of Rhodopseudomonas viridis contains extensive, regular
      arrays of photoreceptor complexes arranged on a hexagonal lattice with a repeat
      distance of 130 A. Single membrane sheets were obtained by mild treatment of the
      thylakoid fraction with the detergent Triton X-100. Heavy metal shadowing and
      electron microscopy of isolated thylakoids indicated a strong asymmetry of the
      membrane, showing a smooth plasmic and a rough exoplasmic side. Fourier
      processing of rotary-shadowed specimens showed the different surface relief on
      both sides of the membrane. Structural units on both sides were roughly circular
      and showed 6-fold symmetry at a resolution close to 20 A. The structural unit was
      characterised by a central core that seemed to extend through the membrane,
      protruding on the exoplasmic side. The core was surrounded by a ring showing 12
      subunits on the plasmic side. Rotary-shadowed as well as negatively-stained
      membranes indicated a handedness of the structure. Treatment of thylakoid
      vesicles with higher detergent concentrations yielded a fraction of particles
      showing the same features as Fourier maps of the structural units. The isolated
      particles therefore appeared to represent structurally intact units of
      photosynthesis.

PMID- 16453517
TI  - Note added in proof.

PMID- 16453516
TI  - Simultaneous rapid chemical synthesis of over one hundred oligonucleotides on a
      microscale.
AB  - An inexpensive, extremely rapid manual method for simultaneous synthesis of large
      numbers of oligodeoxyribonucleotides on 50 or 150 nanomole scale is described.
      The oligonucleotides are assembled in parallel by the phosphotriester method on
      small cellulose paper disks in a simple gas pressure-controlled continuous-flow
      system. For each addition of a nucleotide the disks are sorted into four sets
      which are placed in four columns for addition of A, C, G and T, respectively.
      During one 2-week period, three rounds of synthesis by this method yielded 254
      oligomers (8- to 22-mers), many of which were also purified during this time.
      Using 50 nanomole scale reactions the yields for 17-mers, for example, were in
      the range of 0.5 O.D.(260) units ( 5 nmol, i.e., 10% yield), an amount sufficient
      for most purposes. The equipment required is relatively inexpensive and for the
      most part usually already available in molecular biology laboratories. All
      chemicals are commercially available and the current reagent cost per
      oligonucleotide (25 mug, average length 17-mer) is 3 US dollars.

PMID- 16453518
TI  - Homologous sequences in non-structural proteins from cowpea mosaic virus and
      picornaviruses.
AB  - Computer analyses have revealed sequence homology between two non-structural
      proteins encoded by cowpea mosaic virus (CPMV), and corresponding proteins
      encoded by two picornaviruses, poliovirus and foot-and-mouth disease virus. A
      region of 535 amino acids in the 87-K polypeptide from CPMV was found to be
      homologous to the RNA-dependent RNA polymerases from both picornaviruses, the
      best matches being found where the picornaviral proteins most resemble each
      other. Additionally, the 58-K polypeptide from CPMV and polypeptide P2-X from
      poliovirus contain a conserved region of 143 amino acids. Based on the homology
      observed, a genetic map of the CPMV genome has been constructed in which the 87-K
      polypeptide represents the core polymerase domain of the CPMV replicase. These
      results have implications for the evolution of RNA viruses, and mechanisms are
      discussed which may explain the existence of homology between picornaviruses
      (animal viruses with single genomic RNAs) and comoviruses (plant viruses with two
      genomic RNAs).

PMID- 16453519
TI  - The 17-kb Tam1 element of Antirrhinum majus induces a 3-bp duplication upon
      integration into the chalcone synthase gene.
AB  - The DNA sequence of the termini and the flanking regions of the 17-kb
      transposable element Tam1 was determined. Tam1 is integrated in the chalcone
      synthase gene of the niv-53 mutant of Antirrhinum majus. The element has a 13-bp
      perfect inverted repeat at its termini and appears to induce a 3-bp duplication
      of the target site upon integration. The DNA sequence of a niv revertant was
      analyzed and found to differ from the wild-type sequence by an additional 2 bp
      that seem to derive from the target site duplication. Stretches of homologous
      sequences have been found between the ends of Tam1, within each terminus of the
      element, and between the termini and target site sequences. Structural
      similarities between the ends of Tam1 and the Spm-18 element of Zea mays reflect
      a possible horizontal spread of a common progenitor.

PMID- 16453521
TI  - Note added in proof.

PMID- 16453522
TI  - Note added in proof.

PMID- 16453520
TI  - The Spm (En) transposable element controls the excision of a 2-kb DNA insert at
      the wx allele of Zea mays.
AB  - The waxy (Wx) locus of Zea mays was cloned from strains carrying the wild-type
      and wx mutant alleles. The receptor component of the Suppressor-Mutator (Spm)
      controlling element system in the wx allele was shown to be a 2 kb long insertion
      within the transcribed region of the Wx gene. The insertion, termed Spm-I8, is
      excised during somatic reversion events induced by the autonomous controlling
      element Enhancer (En), which is an equivalent to Spm. Integration of Spm-I8 into
      the Wx gene generates a 3-bp target site duplication. Spm-I8 has a 13 bp long
      inverted repeat at its termini. The ends of the element can be further folded to
      build a large double-stranded structure consisting of five perfectly matching
      double-stranded regions of 9-13 bp in length, interrupted by single-stranded
      loops. A comparison of the wild-type and wx alleles revealed two additional
      insertions 6 (insert-1) and 0.25 (insert-2) kb in length. No En-induced excision
      of insert-1 and insert-2 could be detected so far. There is remarkable structure
      and sequence homology between Spm-I8 and the transposable elements Tam1 and Tam2
      of Antirrhinum majus at their termini, reflecting a possible evolutionary and/or
      functional relationship between transposons in different plant species.

PMID- 16453523
TI  - Note added in proof.

PMID- 16453525
TI  - Note added in proof.

PMID- 16453524
TI  - The molecular basis for the differential translation of TMV RNA in tobacco
      protoplasts and wheat germ extracts.
AB  - Translation of tobacco mosaic virus (TMV) RNA in tobacco protoplasts yields the
      17.5-K coat protein, a 126-K protein and a 183-K protein which is generated by an
      efficient readthrough over the UAG termination codon at the end of the 126-K
      cistron. In wheat germ extracts, however, only the 5'-proximal 126-K cistron is
      translated whereas the 183-K readthrough protein is not synthesized. Purification
      and sequence analysis of the endogenous tyrosine tRNAs revealed that the
      uninfected tobacco plant contains two tRNAs, both with GPsiA anticodons which
      stimulate the UAG readthrough in vitro and presumably in vivo. In contrast, 85%
      of the tRNA from wheat germ contains a QPsiA anticodon and 15% has a GPsiA
      anticodon. Otherwise the sequences of tRNAs from wheat germ and tobacco are
      identical. UAG readthrough and hence synthesis of the 183-K protein is only
      stimulated by tRNA(GPsiA) and not at all by tRNA(QPsiA). The tRNAs from wheat
      leaves were also sequenced. This revealed that adult wheat contains tRNA(GPsiA)
      only. This is very much in contrast to the situation in animals, where Q
      containing tRNAs are characteristic for adult tissues whereas Q deficiency is
      typical for the neoplastic and embryonic state.

PMID- 16453526
TI  - Note added in proof.

PMID- 16453527
TI  - Note added in proof.

PMID- 16453529
TI  - Note added in proof.

PMID- 16453528
TI  - The zeste-white interaction: induction and genetic analysis of a novel class of
      zeste alleles.
AB  - The recovery and analysis of a novel class of zeste mutations is described. z and
      z do not require two w genes for their expression unless the z gene is present.
      Analysis of genetic interactions among zeste alleles proved that z mutations are
      strong antagonists of the z gene product. z is readily reverted by X-rays or by
      ethylmethane sulphonate to a range of intermediate zeste alleles and thus it is
      considered to be an insertional mutation. We suggest that z and op mutations
      arose as a result of insertions in a presumptive control region, and two
      alternative models for the structure of the zeste locus are evaluated.

PMID- 16453530
TI  - Heteromultimeric structure of the nitrate reductase complex of Chlamydomonas
      reinhardii.
AB  - The NAD(P)H-nitrate reductase complex (overall-NR) of Chlamydomonas reinhardii
      exhibits two partial activities: NAD(P)H-cytochrome c reductase (diaphorase) and
      reduced benzyl viologen-NR (terminal-NR). Mild tryptic digestion of the enzyme
      complex resulted in the loss of both overall and terminal-NR activities, whereas
      diaphorase activity remained unaltered. The diaphorase activity of mutant 104 and
      the terminal-NR activity of mutant 305 of C. reinhardii, which are the sole
      activities related to NR present in these mutants, responded to tryptic treatment
      to the same extent as the corresponding activities of the wild enzyme complex.
      Trypsin disassembled the 220-kd NR native complex by destroying the aggregation
      capability of the diaphorase subunits without affecting their activity nor
      molecular size (45 kd). A 67-kd thermostable protein, containing molybdenum co
      factor, was also released from trypsin-treated NR. This protein lacked diaphorase
      and NR activities but was able to reconstitute the overall-NR complex by
      complementation with untreated diaphorase subunit of mutant 104. Our results
      support a tetrameric structure for the C. reinhardii NR complex, containing two
      kinds of subunits.

PMID- 16453533
TI  - Co-transfection of normal NIH/3T3 DNA and retroviral LTR sequences: a novel
      strategy for the detection of potential c-onc genes.
AB  - [This corrects the article on p. 1121 in vol. 3, PMID: 6329737.].

PMID- 16453531
TI  - A second cauliflower mosaic virus gene product influences the structure of the
      viral inclusion body.
AB  - We have used electron microscopy of thin sections and experiments on isolated
      viroplasms to compare the properties of four strains of cauliflower mosaic virus
      (CaMV), three of which were partially or completely deleted in open reading frame
      (ORF) II. Our results confirm that this gene is required for aphid
      transmissibility and show that the product of ORF II influences the firmness with
      which virions are held within the viroplasm. Analysis of the proteins in the
      viroplasms showed that a mutant with a partial deletion in ORF II produced a
      protein smaller than the normal ORF product. This smaller protein was non
      functional with respect both to aphid transmissibility and properties of the
      viroplasms.

PMID- 16453535
TI  - Note added in proof.

PMID- 16453534
TI  - Cowpea mosaic virus VPg: sequencing of radiochemically modified protein allows
      mapping of the gene on B RNA.
AB  - A partial amino acid sequence of cowpea mosaic virus (CPMV) VPg radiochemically
      modified by chloramine-T and Bolton-Hunter reagent has been determined. VPg
      covalently bound to viral RNA chains (VPg-RNA) was iodinated with chloramine-T
      and Bolton-Hunter reagent to label tyrosine and lysine residues, respectively.
      [I]VPg-RNA was digested with nuclease P1 and the resulting [I]VPg-pU was purified
      by SDS-polyacrylamide gel electrophoresis and subjected to automated Edman
      degradation. Control experiments with chemically synthesized poliovirus VPg
      showed the feasibility of radiochemical microsequence analysis of protein that
      had been radiochemically modified by chloramine-T and Bolton-Hunter reagent.
      Analysis of CPMV [I]VPg-pU revealed the presence of tyrosine residues at position
      12 and 14, and of lysine residues at position 3 and 20, respectively. In
      combination with Edman degradation of unlabeled CPMV VPg, which showed serine and
      arginine residues to be present at position 1 and 2, respectively, the data
      obtained allow the precise positioning of VPg within the 200 000 dalton (200 K)
      polyprotein encoded by CPMV B RNA and the prediction of its entire amino acid
      sequence. VPg is located at the COOH terminus of its 60 K, membrane
      bound,precursor and proximal to the amino terminus of the protease-polymerase
      domain of the polyprotein. A processing scheme for the 200 K polyprotein is
      discussed in which Gln-Ser amino acid pairs act as the major signal for
      proteolytic cleavage.

PMID- 16453536
TI  - Widespread occurrence of polypeptides related to neurotubule-associated proteins
      (MAP-1 and MAP-2) in non-neuronal cells and tissues.
AB  - [This corrects the article on p. 991 in vol. 3, PMID: 6376120.].

PMID- 16453537
TI  - Life by a new decarboxylation-dependent energy conservation mechanism with Na as
      coupling ion.
AB  - We report here a new mode of ATP synthesis in living cells. The anaerobic
      bacterium Propionigenium modestum gains its total energy for growth from the
      conversion of succinate to propionate according to: succinate + H(2)O -->
      propionate + HCO(3) ( big up tri, openG' = -20.6 kJ/mol). The small free energy
      change of this reaction does not allow a substrate-linked phosphorylation
      mechanism, and no electron transport phosphorylation takes place. Succinate was
      degraded by cell-free extracts to propionate and CO(2) via succinyl-CoA, methyl
      malonyl-CoA and propionyl-CoA. This pathway involves a membrane-bound
      methylmalonyl-CoA decarboxylase which couples the exergonic decarboxylation with
      a Na ion transport across the membrane. The organism also contained a membrane
      bound ATPase which was specifically activated by Na ions and catalyzed and
      transport of Na ions into inverted bacterial vesicles upon ATP hydrolysis. The
      transport was abolished by monensin but not by the uncoupler carbonylcyanide-p
      trifluoromethoxy phenylhydrazone. Isolated membrane vesicles catalyzed the
      synthesis of ATP from ADP and inorganic phosphate when malonyl-CoA was
      decarboxylated and malonyl-CoA synthesis from acetyl-CoA when ATP was hydrolyzed.
      These syntheses were sensitive to monensin which indicates that Na functions as
      the coupling ion. We conclude from these results that ATP synthesis in P.
      modestum is driven by a Na ion gradient which is generated upon decarboxylation
      of methylmalonyl-CoA.

PMID- 16453538
TI  - Expression of foreign genes in regenerated plants and in their progeny.
AB  - Chimeric genes comprised of the nopaline synthase promoter and bacterial coding
      sequences specifying resistance to kanamycin, chloramphenicol or methotrexate,
      were inserted into the non-oncogenic Ti plasmid vector pGV3850 by recombination
      (through homologous pBR322 sequences present in the chimeric gene constructs and
      pGV3850). These co-integrates in Agrobacterium were used to infect single plant
      protoplasts of Nicotiana by co-cultivation. The resistance traits allowed the
      selection of transformed calli in tissue culture in the presence of the
      appropriate antibiotic. Furthermore, as a non-oncogenic Ti plasmid was used for
      the protoplast transformation, phenotypically normal and fertile plants could be
      regenerated from the resistant calli. We have shown that these fully
      differentiated plant tissues exhibit functional expression of resistance traits
      (Km and Cm). All plants carrying the chimeric genes developed normally, flowered,
      and set seeds. The inheritance of several of these resistance traits was analyzed
      and shown to be Mendelian. These results are model experiments to demonstrate
      that genes of interest can be systematically transferred to the genome of plants
      using non-oncogenic Ti plasmid derivatives; and that transformed plants are
      capable of normal growth and differentiation, thus providing a natural
      environment for the study of gene expression and development of plant cells.

PMID- 16453539
TI  - Transcription of the soybean leghemoglobin genes during nodule development.
AB  - During the early stages of soybean nodule development the leghemoglobin (Lb)
      genes are activated sequentially in the opposite order to which they are arranged
      in the soybean genome. At a specific stage after the initial activation of all
      the Lb genes, a large increment occurs in the transcription of the Lb(c1), Lb(c3)
      and Lb(a) genes while the transcription of the Lb(c2) gene is not amplified to a
      similar extent. All the Lb genes retain significant activity for a long period
      during the lifetime of a nodule. Consequently the soybean Lb genes are not
      regulated by a developmental gene switching mechanism as is the case for
      vertebrate globin genes. Concomitantly with the increase in Lb gene transcription
      some of the other nodule specific plant genes are activated. These specific
      changes in the activities of the Lb and nodulin genes precede the activation of
      the bacterial nitrogenase gene. Thus the alteration in bacterial metabolism due
      to nitrogen fixation is not responsible for the observed changes in the
      transcriptional activities of the Lb and nodule-specific genes.

PMID- 16453540
TI  - DNA sequence requirements for the accurate transcription of a protein-coding
      plastid gene in a plastid in vitro system from mustard (Sinapis alba L.).
AB  - A nuclease-treated plastid extract from mustard (Sinapis alba L.) allows
      efficient transcription of cloned plastid DNA templates. In this in vitro system,
      the major runoff transcript of the truncated gene for the 32 000 mol. wt.
      photosystem II protein was accurately initiated from a site close to or identical
      with the in vivo start site. By using plasmids with deletions in the 5'-flanking
      region of this gene as templates, a DNA region required for efficient and
      selective initiation was detected 28-35 nucleotides upstream of the transcription
      start site. This region contains the sequence element TTGACA, which matches the
      consensus sequence for prokaryotic ;-35' promoter elements. In the absence of
      this region, a region 13-27 nucleotides upstream of the start site still enables
      a basic level of specific transcription. This second region contains the sequence
      element TATATAA, which matches the consensus sequence for the ;TATA' box of genes
      transcribed by RNA polymerase II (or B). The region between the ;TATA'-like
      element and the transcription start site is not sufficient but may be required
      for specific transcription of the plastid gene. This latter region contains the
      sequence element TATACT, which resembles the prokaryotic ;-10' (Pribnow) box.
      Based on the structural and transcriptional features of the 5' upstream region, a
      ;promoter switch' mechanism is proposed, which may account for the
      developmentally regulated expression of this plastid gene.

PMID- 16453541
TI  - Mapping of the protein-coding regions of Rhizobium meliloti common nodulation
      genes.
AB  - An 8.5-kb EcoRI fragment containing the common nod region of the megaplasmid
      pRme41b of Rhizobium meliloti was recloned in plasmids of Escherichia coli, and a
      detailed restriction map was established. The region can express at least eight
      proteins in E. coli minicells and in an in vitro transcription/translation
      system, prepared from E. coli. Protein coding regions were determined by
      subcloning of restriction fragments, deletion mutations and by transposon
      mutagenesis. The coding regions for at least three polypeptide chains (mol. wts.
      23 000, 28 500 and 44 000) were mapped on a 3.3-kb nod gene cluster. The 44 000
      mol. wt. protein is expressed from a nod region, which is highly conserved in two
      Rhizobium species. The protein map of the 8.5-kb fragment was correlated to a map
      of insertion mutations with Nod and Fix phenotypes. The data suggest that the
      proteins encoded by the nod gene cluster may be involved in early steps of the
      nodulation process. Nod Fix symbiotic mutations were localized in the coding
      region for a 33 000 mol. wt. protein, suggesting that this polypeptide might be a
      fix gene product.

PMID- 16453542
TI  - Analysis of sh-m6233, a mutation induced by the transposable element Ds in the
      sucrose synthase gene of Zea mays.
AB  - The unstable allele sh-m6233 caused by insertion of the transposable element Ds
      into the sucrose synthase gene of maize, was cloned. The mutation is caused by
      the insertion of an 4 kb DNA segment, consisting of two identical Ds elements of
      2000 bp length, of which one is inserted into the center of the other in inverted
      orientation. This structure is, at the level of restriction mapping and partial
      DNA sequencing, identical to the double Ds element found in a larger insert in
      the mutant allele sh-m5933. 8 bp of host DNA are duplicated upon insertion. In a
      revertant, a 6-bp duplication is retained.

PMID- 16453544
TI  - Note added in proof.

PMID- 16453543
TI  - Sequence analysis of the insertion element ISH1.8 and of associated structural
      changes in the genome of phage PhiH of the archaebacterium Halobacterium
      halobium.
AB  - We have sequenced the insertion element ISH1.8 which can be present in one or two
      copies in the genome of phage PhiH of Halobacterium halobium. ISH1.8 is 1895 bp
      long, has no inverted repeat at its ends, and one only of the two copies is
      flanked by two 5-bp duplications. An 8-bp sequence composed of 4 bp from each end
      of ISH1.8 is present in both sites lacking the element. This 8-bp sequence could
      either be a specific insertion sequence or a part of the element that is left
      behind upon deletion. The plasmid pPhiHL, consisting of the invertible L segment
      of the phage genome which is, in PhiH2 and PhiH5, flanked by two copies of
      ISH1.8, contains 112 bp of ISH1.8 and is released from the phage genome by
      recombination within a direct repeat of 9 bp. This 9-bp sequence (TCCCGCCCT)
      exists as an inverted repeat in ISH1.8 and therefore as two distinct repeats in
      phage genomes containing two copies of ISH1.8 in inverted orientation.

PMID- 16453546
TI  - Note added in proof.

PMID- 16453545
TI  - Subcellular site of lectin synthesis in developing rice embryos.
AB  - Embryos of developing rice (Oryza sativa L. cv. Koshihikari) caryopses which
      actively synthesize lectin were labelled with [S]cysteine for different times and
      newly synthesized rice lectin was isolated by affinity chromatography. Gel
      filtration of embryo extracts on Sepharose-4B indicated that a large portion of
      the labelled lectin was associated with the particulate fraction. Experiments
      with detergent indicated that this lectin was sequestered within organelles. When
      extracts of pulse-labelled embryos were fractionated on isopycnic sucrose
      gradients, this detergent-released lectin banded in the same density-region as
      the endoplasmic reticulum (ER) marker enzyme NADH-cytochrome c reductase. Both
      radioactivity in rice lectin and the enzyme activity shifted towards a higher
      density in the presence of 2 mM Mg acetate, indicating that the labelled lectin
      was associated with the rough ER. The ER-bound lectin could be chased from this
      organelle when tissue was incubated in unlabelled cysteine following a 1 h pulse
      of labelled cysteine. Radioactivity chased out of the ER with a half-life of 4 h
      and accumulated in the soluble fraction. In the ER the lectin was present as a
      polypeptide with mol. wt. 23 000, while in the soluble fraction it occurred as
      polypeptides with mol. wt. 18 000, 10 000 and 8000. The rice lectin in the ER is
      capable of binding carbohydrates since it binds readily to the affinity gels. It
      is associated into dimers with an approximate mol. wt. of 46 000. The results
      show that newly synthesized rice lectin is transiently sequestered within the ER
      before further transport and processing take place.

PMID- 16453547
TI  - Insect immunity. The primary structure of the antibacterial protein attacin F and
      its relation to two native attacins from Hyalophora cecropia.
AB  - The attacins are antibacterial proteins present in the hemolymph of the pupae of
      the silk moth Hyalophora cecropia after bacterial infection. We present the
      primary structure of one attacin, the F form. We show that this protein is
      derived by proteolysis from the native protein, attacin E. Using a method for
      rapid purification from the hemolymph of immunized pupae of the neutral attacin E
      and a basic attacin, both proteins were found in freshly collected immune
      hemolymph. We conclude that they are the native products of two attacin genes,
      the existence of which was inferred from the isolation of two cDNA clones as
      described in the accompanying paper. The two proteins, which differed in their
      pIs (7 and 9), were found to have similar mol. wts. (20 000) and closely related
      primary structures, displaying a total of 40 amino acid substitutions, 12 of
      which were of a non-conservative nature.

PMID- 16453548
TI  - Insect immunity. Isolation and sequence of two cDNA clones corresponding to
      acidic and basic attacins from Hyalophora cecropia.
AB  - The Cecropia moth has three known classes of antibacterial immune proteins,
      attacins, lysozyme and cecropins (earlier referred to as P5, P7 and P9,
      respectively). Six attacins with different isoelectric points have been purified.
      The N-terminal sequences for five of these forms imply that only two different
      genes exist. We have now isolated and sequenced two cDNA clones, one for the
      basic attacin and one for the acidic form. The two mature proteins show 76%
      homology at the nucleotide level, while the regions beyond the stop codons are
      36% homologous. The differences in the content of aspartic acid accounts for the
      difference in net charge between the acidic and basic attacin. Further
      differences in charge can be obtained by post-translational removal of a lysine
      containing tetrapeptide at the C-terminal end of the two proteins. Evidence for a
      prepro form of the basic attacin is presented.

PMID- 16453549
TI  - Functional analysis of the white gene of Drosophila by P-factor-mediated
      transformation.
AB  - A 12-kb DNA segment spanning the white (w) locus of Drosophila has been inserted
      into a P-transposon vector and used for P-factor-mediated germ-line
      transformation. Several red-eyed transformants were recovered which complement
      the white mutant phenotype. Analysis of the eye pigments and the interaction with
      the zeste mutation indicates that the w gene inserted at several new chromosomal
      sites is expressed normally. The tissue-specific accumulation of w transcripts,
      as studied by in situ hybridization to tissue sections, is the same in
      transformant and wild-type larvae. This indicates that all the genetic
      information specified by the w locus is contained within this 12-kb segment of
      DNA. By secondary mobilization it was shown that the w sequences have been
      inserted as a functional P(w) transposon which is capable of further
      transposition.

PMID- 16453550
TI  - Developmental expression of the white locus of Drosophila melanogaster.
AB  - We have isolated several cDNA clones of the white locus which are derived from
      embryonic and pupal transcripts of Drosophila melanogaster. The cDNA sequences
      map within 7.5 kb (coordinates -3.0 to +4.6) of the genomic DNA and correspond
      mainly to sequences within the distal region of the gene (coordinates -0.2 to 
      3.0). A major RNA species of 2.6 kb was detected on Northerns of poly(A) RNA
      isolated from all developmental stages. The total accumulation of this transcript
      peaks in the mature third instar larva to a level of 0.003% which is about ten
      times higher than that observed in embryos. The spatial distribution of white
      locus transcripts was determined by in situ hybridization to tissue sections. In
      embryos, hybridization signals are restricted to the cells of the developing
      Malpighian tubules and the signal strength corresponds with 50 transcripts per
      cell. Before the termination of the third instar stage, hybridization signals are
      also detected at a comparable level in the eye antennal disks. At the same stage,
      a third site of labeling is observed over a small cluster of cells which seems to
      be associated with the larval photoreceptor organs. Thus, white locus expression
      is largely restricted to tissues which are known to be involved in the
      biosynthesis of eye pigments and these different cell types act in a temporally
      autonomous manner with respect to the induction of the white gene during
      development.

PMID- 16453551
TI  - New actin-binding proteins from Dictyostelium discoideum.
AB  - Dictyostelium discoideum contains a soluble actin-binding protein that caps actin
      filaments at their fast growing ends. The purified protein consists of two
      subunits with 34 kd and 32 kd apparent mol. wts. Like similar proteins from
      Acanthamoeba and bovine brain the capping protein from D. discoideum acts in a Ca
      -independent manner. It lacks severing activity as indicated by its inability to
      disrupt the stress fibers and the microfilament network in detergent-extracted
      cells. Two actin-binding proteins from a plasma membrane-enriched fraction were
      labeled with [I]actin using a gel overlay technique. One of these proteins, with
      an apparent mol. wt. of 17 kd in SDS-polyacrylamide gels, has been purified from
      high-salt extracts, the other protein with an apparent mol. wt. of 31 kd has been
      purified from Triton X-100 extracted membranes. Monoclonal antibodies were raised
      against D. discoideum severin, alpha-actinin, the larger subunit of the capping
      protein, and the 17-kd membrane-associated protein. Immunoblotting of proteins
      from whole cell lysates showed that all these actin-binding proteins were present
      in both growth phase and aggregation-competent cells.

PMID- 16453552
TI  - Sequence analysis of a split gene involved in fruiting from the fungus
      Schizophyllum commune.
AB  - The sequence of a gene and its mRNA, which is abundantly expressed during
      fruiting body initiation in the Basidiomycete Schizophyllum commune, is
      described. This gene (1G2), the first to be analyzed in this group of fungi,
      contains an open reading frame coding for a polypeptide of 94 amino acids and a
      mol. wt. of 9842. A possible signal peptide of 20 residues and one glycosylation
      site were found. The sequence analysis was hampered by a sequence rearrangement
      in one of the cDNA clones, probably due to base pairing between short
      complementary sequences present at the 5' and 3' ends of the mRNA. The 5'
      untranslated leader sequence is 57 bp long and harbors a possible ribosome
      binding site close to the AUG start codon. A TATA box is found at position -31
      upstream of transcription initiation. The 3' untranslated sequence is 200 bp long
      and contains the sequence -TATATAAT-, which most likely represents the
      polyadenylation signal. Some heterogeneity as to the site of addition of the
      poly(A) tail was observed. The coding region of the gene is interrupted by three
      very small introns of 53, 49 and 49 bp, respectively. The 5' and 3' splice
      junctions are conserved: GTGAGT- and -AG-, respectively. Each intron contains a
      sequence complementary to the 5' end of the intron. These sequences are compared
      with internal conserved sequences in yeast and filamentous fungi with regard to
      their possible role in splicing.

PMID- 16453554
TI  - Note added in proof.

PMID- 16453555
TI  - SAV 1, a temperate u.v.-inducible DNA virus-like particle from the
      archaebacterium Sulfolobus acidocaldarius isolate B12.
AB  - Sulfolobus acidocaldarius, strain B12, which harbours a double-stranded DNA
      species both as a plasmid and in a linear form, which is integrated at a specific
      site of the chromosome, produces virus-like particles upon u.v. irradiation.
      These particles contain the same circular DNA and a number of coat proteins and
      are probably surrounded by a lipid membrane. They are lemon shaped, 100 x 60 nm
      in size and carry tail structures at one pole. The host cell recovers and remains
      lysogenic after virus production. Though a large fraction of liberated particles
      is found attached to structures derived from the cells, neither adsorption nor
      infection of a number of Sulfolobus isolates has so far been observed.

PMID- 16453553
TI  - The apocytochrome b gene in maize mitochondria does not contain introns and is
      preceded by a potential ribosome binding site.
AB  - The apocytochrome b (COB) gene has been isolated from maize (Zea mays L.)
      mitochondrial DNA. Sequence analysis reveals that the coding region of the gene
      is 1164 bp long and, in contrast with the homologous gene from yeast, does not
      contain introns or TGA (Trp) codons. The predicted polypeptide encoded by the
      gene has a mol. wt. of 42 868 daltons, and shows 48% amino acid sequence homology
      with the corresponding yeast and mammalian polypeptides. Hydropathic profiles of
      the polypeptide indicate the presence of nine, membrane spanning hydrophobic
      domains suggesting that it is organised in the inner mitochondrial membrane in a
      similar fashion to that proposed for apocytochrome b in other organisms. The COB
      gene is preceded by a sequence 5' -AGTTGTCA-3' which may act as a ribosome
      binding site in the mRNA since: (i) it shows 67.5% complementarity with an
      octanucleotide at the 3' end of the maize mitochondrial 18S rRNA, located in a
      position homologous to that of the Escherichia coli Shine and Dalgarno sequence,
      and (ii) a similar sequence precedes several other plant mitochondrial genes at a
      distance of 15-20 nucleotides from the ATG initiation codon. RNA transcript
      analysis shows that the gene is transcribed in a complex manner with the presumed
      mature mRNA ( 2.25 kb) probably being derived by sequential processing from a
      larger primary transcript.

PMID- 16453556
TI  - Note added in proof.

PMID- 16453557
TI  - Complete nucleotide sequence of the infectious cloned DNA components of tomato
      golden mosaic virus: potential coding regions and regulatory sequences.
AB  - The nucleotide sequences of the infectious cloned DNA components of tomato golden
      mosaic virus (TGMV) have been determined. DNA A (2588 nucleotides) and DNA B
      (2508 nucleotides) have little sequence homology except for a region of 200 bases
      which is almost identical in the two molecules. Analysis of open reading frames
      revealed six potential coding regions for proteins of mol. wt. >10 000, four in
      DNA A and two in DNA B. Possible regulatory signals are identified and a model
      for bidirectional transcription of the two genome components is presented.
      Comparison of the nucleotide sequences of the DNAs of TGMV and cassava latent
      virus (CLV) revealed a fairly close relationship between TGMV DNA A and CLV DNA 1
      and a comparatively distant relationship between TGMV DNA B and CLV DNA 2. All
      the potential coding regions in the TGMV DNAs had counterparts in the CLV DNAs
      suggesting an overall similarity in genome organisation, but six potential coding
      regions in the CLV DNAs had no counterparts in the TGMV DNAs. The 200-base region
      common to the two DNAs of each virus had little sequence homology, except for a
      highly conserved 33-base sequence potentially capable of forming a stable hairpin
      structure.

PMID- 16453559
TI  - Isolation and characterisation of arthropod gap junctions.
AB  - Gap junctions have been isolated from the hepatopancreas of the crustacean
      arthropod, Nephrops norvegicus (Norway lobster). SDS-PAGE of these preparations
      shows two major protein bands, mol. wt. 18 000 (18 K) and mol. wt. 28 000 (28 K).
      The 18-K and 28-K proteins are interconvertible, cannot be distinguished by two
      dimensional tryptic and chymotryptic peptide mapping, and therefore appear to be
      different (most likely monomeric and dimeric) forms of the same protein. The
      protein can also aggregate to higher multimeric forms mol. wt. 38 000 (presumed
      trimer), and mol. wt. 52 000 (presumed tetramer). The buoyant density of the
      isolated gap junctions in continuous potassium iodide gradients is 1.260 g/cm.
      The junctions are progressively solubilized in increasing SDS concentrations,
      mostly between 0.1% and 0.2% SDS, and this is accompanied by the release of the
      18-K and 28-K forms of the junctional protein. The Nephrops hepatopancreas 18-K
      junctional protein has antigenic determinants in common with the vertebrate 16-K
      junctional protein as shown by cross-reactivity with two different affinity
      purified antibody preparations. However, no detectable similarity can be seen
      between the major I-labelled tryptic and chymotrytpic peptides of the Nephrops
      hepatopancreas 18-K protein and the mouse liver 16-K protein.

PMID- 16453560
TI  - Note added in proof.

PMID- 16453561
TI  - Gin-mediated site-specific recombination in bacteriophage Mu DNA: overproduction
      of the protein and inversion in vitro.
AB  - Inversion of the G segment in bacteriophage Mu DNA occurs by a site-specific
      recombination event and determines the host specificity of Mu phage particles
      produced. Inversion is mediated by a Mu function (Gin). The gin gene has been
      placed under control of the inducible lambda pL promoter and a synthetic Shine
      Dalgarno linker upstream of the initiation codon. The Gin protein content in
      induced cells is boosted to 10% of total protein. Partially purified extracts
      from overproducing strains promote efficient inversion of the G DNA segment in
      vitro which is visualized by agarose gel electrophoresis of the substrate DNA
      after cutting with appropriate restriction endonucleases. The in vitro reaction
      requires Mg, a super-coiled DNA substrate and occurs in the absence of exogenous
      ATP. Inversion from the G(+) to the G(-) orientation is as efficient as the
      switch from G(-) to G(+).

PMID- 16453562
TI  - Delivery of T-DNA from the Agrobacterium tumefaciens chromosome into plant cells.
AB  - The intact T-region of the B6Ti plasmid of Agrobacterium tumefaciens was stepwise
      cloned into a site in transposon Tn3. In this way a suitable vehicle (Tn1882) was
      obtained for translocating the T-region to different replicons, i.e., to other
      plasmids or the chromosome. The IncP plasmid R772::Tn1882 conferred
      tumorigenicity on Agrobacterium if the virulence genes were provided in trans in
      the same cell. This result showed that the T-region present on Tn1882 was
      transferred efficiently to plant cells. Normal tumor development also occurred if
      the T-region was placed in the chromosome of A. tumefaciens and an R' plasmid was
      present carrying virA-E or virA-F. We conclude that the plasmid location of the T
      region is not a prerequisite for transfer to the plant cell. The apparently
      normal delivery of the T-DNA from a bacterial chromosomal location supports a
      model involving a processing step within Agrobacterium effecting transfer of the
      T-region as a separate entity.

PMID- 16453564
TI  - Note added in proof.

PMID- 16453565
TI  - The wheat cytochrome oxidase subunit II gene has an intron insert and three
      radical amino acid changes relative to maize.
AB  - We have determined the sequence of the wheat mitochondrial gene for cytochrome
      oxidase subunit II (COII) and find that its derived protein sequence differs from
      that of maize at only three amino acid positions. Unexpectedly, all three
      replacements are non-conservative ones. The wheat COII gene has a highly
      conserved intron at the same position as in maize, but the wheat intron is 1.5
      times longer because of an insert relative to its maize counterpart.
      Hybridization analysis of mitochondrial DNA from rye, pea, broad bean and
      cucumber indicates strong sequence conservation of COII coding sequences among
      all these higher plants. However, only rye and maize mitochondrial DNA show
      homology with wheat COII intron sequences and rye alone with intron-insert
      sequences. We find that a sequence identical to the region of the 5' exon
      corresponding to the transmembrane domain of the COII protein is present at a
      second genomic location in wheat mitochondria. These variations in COII gene
      structure and size, as well as the presence of repeated COII sequences,
      illustrate at the DNA sequence level, factors which contribute to higher plant
      mitochondrial DNA diversity and complexity.

PMID- 16453563
TI  - The DNA sequence analysis of soybean heat-shock genes and identification of
      possible regulatory promoter elements.
AB  - The soybean possesses a gene family encoding the major low mol. wt. heat-shock
      proteins of 15-18 kd. We have determined the primary DNA sequences of two of the
      genes, both located on the same subgenomic DNA fragment. The protein coding
      regions are characterized by long uninterrupted open reading frames and by
      sequence homology of 92% and 100% with a heat-shock specific cDNA. One protein
      sequence deduced from the completely cloned gene hs6871 is composed of 153 amino
      acids with a total mol. wt. of 17.3 kd; the other protein is a truncated
      polypeptide containing 73 amino acids at the carboxy-terminal end of an
      incompletely cloned heat-shock gene designated hs6834. Investigations of the
      hydrophilic/hydrophobic characteristics of the polypeptides revealed a
      conservation of structural features between heat-shock proteins from soybean,
      Caenorhabditis and Drosophila and mammalian lens alpha-crystallin. The 5' end of
      the soybean heat-shock gene hs6871 was mapped by S1 nuclease at a position which
      is 100 nucleotides upstream from the translation start codon and 25 nucleotides
      downstream from a TATA-box sequence. Six other potential promoter elements which
      are homologous to the Drosophila heat-shock consensus sequence CT-GAA-TTC-AG-,
      are present within 150 nucleotides upstream from the TATA-box. The possible
      functions of these promoter elements in transcriptional regulation of expression
      of soybean heat-shock gene are discussed.

PMID- 16453567
TI  - Note added in proof.

PMID- 16453566
TI  - Genetic activity along 315 kb of the Drosophila chromosome.
AB  - Transcripts from different tissues were mapped along a 315 kb segment of the
      Drosophila chromosome, a region which includes the rosy and Ace loci. Forty-three
      distinct RNA species were detected, though only 12 recessive lethal
      complementation groups had been mapped in the interval. The sum of the sizes of
      the transcripts covers 33% of the genomic DNA. The distribution of transcription
      units along the walk is very uneven. Sixty-three kb of genomic DNA at the
      proximal end of the walk encode 18 transcripts, while only seven are found in the
      next 153 kb. Each tissue exhibits a specific spectrum of transcripts. No
      clustering was seen among genes expressed coordinately. In salivary glands, the
      number of transcripts detected corresponds to the number of chromomeric units in
      the polytene chromosomes of this tissue. Moreover, the density distribution of
      transcripts along the DNA walk is parallel to the density distribution of
      chromomeric units.

PMID- 16453569
TI  - Note added in proof.

PMID- 16453568
TI  - The three-dimensional folding of the tRNA-like structure of tobacco mosaic virus
      RNA. A new building principle applied twice.
AB  - The structure of the tRNA-like 3' terminus of tobacco mosaic virus (TMV) RNA has
      been studied. A 3' -terminal fragment possessing the tRNA-like properties was
      probed with chemical modification and enzymatic digestions. A model of the
      secondary structure is proposed for the last 105 nucleotides. The corresponding
      region of other tobamoviral RNAs can be folded in an identical secondary
      structure. A three-dimensional model for the tRNA-like structure is given which
      is compared with those proposed earlier for the tRNA-like 3' termini of turnip
      yellow mosaic virus (TYMV) RNA and brome mosaic virus (BMV) RNA. A new building
      principle which we discovered previously by studying the latter RNAs appears to
      be applied twice in the tRNA-like structure of TMV RNA. The determination of the
      minimal length requirement for recognition of CTP, ATP:tRNA nucleotidyl
      transferase reveals a size of 100 nucleotides in agreement with the models
      proposed.

PMID- 16453570
TI  - Histone H4 gene is transcribed in S phase but also late in G(2) phase in Physarum
      polycephalum.
AB  - The myxomycete Physarum polycephalum contains two types of H4 histone genes.
      Southern blotting of restriction endonuclease fragments of P. polycephalum DNA
      and hybridization to a cloned probe labelled by nick-translation indicate that
      there are only one or two copies of each H4 gene per haploid genome. A cloned
      homologous genomic probe was used to study the cellular abundance of H4 mRNA
      during the cell cycle. We report that the H4 mRNA is not only transcribed in S
      phase as previously described for other organisms but that transcription of the
      H4 gene also occurs at the end of G(2) phase. Since no translation of the histone
      messenger was observed in G(2) phase this suggests that the histone mRNA
      synthesized in G(2) constitutes a pool of molecules in anticipation of the next S
      phase.

PMID- 16453572
TI  - Note added in proof.

PMID- 16453571
TI  - Wheat germ agglutinin binds to the contact site A glycoprotein of Dictyostelium
      discoideum and inhibits EDTA-stable cell adhesion.
AB  - Wheat germ agglutinin (WGA), a lectin that primarily reacts with N
      acetylglucosamine residues, specifically inhibits the EDTA-stable type of
      intercellular adhesion of aggregation competent Dictyostelium discoideum cells.
      The major WGA-binding protein of these cells is a developmentally-regulated
      glycolipoprotein of 80 kd apparent mol. wt., designated as contact site A. This
      glycoprotein is a target site of antibody fragments that block the EDTA-stable
      cell adhesion, and is characterized by sulfated carbohydrate residues. WGA does
      not significantly bind to glycoproteins of a mutant, HL220, which produces a 68
      kd component in place of the 80-kd glycoprotein. Inhibition of N-glycosylation by
      tunicamycin causes wild-type cells to produce a WGA-binding but unsulfated 66-kd
      component and a non-binding 53-kd component. These results indicate that the 80
      kd glycoprotein contains two classes of carbohydrate residues, a WGA-binding one
      that is defective in HL220, and another, sulfated, one that is absent from the 66
      kd wild-type product; both are missing in the 53-kd protein. WGA and a monoclonal
      antibody that is blocked by N-acetylglucosamine were further used to probe for
      glycoproteins in the multicellular slug stage that share carbohydrate structures 
      and possibly functions - with the contact site A glycoprotein. Glycoproteins in
      the 95-kd range have previously been implicated in cell-to-cell adhesion during
      the slug stage. We distinguished a 95-kd glycoprotein that binds WGA from another
      one that binds antibody.

PMID- 16453573
TI  - Direct gene transfer to plants.
AB  - Evidence for direct, gene-mediated stable genetic transformation of plant cells
      of Nicotiana tabacum is presented. A selectable hybrid gene comprising the
      protein coding region of the Tn5 aminoglycoside phosphotransferase type II gene
      under control of cauliflower mosaic virus gene VI expression signals was
      introduced into plant protoplasts as part of an Escherichia coli plasmid. The
      gene was stably integrated into plant genomic DNA and constitutively expressed in
      selected, drug resistant, protoplast-derived cell clones. The mode of integration
      of the foreign gene into the plant genome resembled that observed for DNA
      transfection of mammalian cells. Plants regenerated from transformed cell lines
      were phenotypically normal and fertile, and they maintained and expressed the
      foreign gene throughout the development of vegetative and generative organs.
      Microspores, grown in anther culture, developed into resistant and sensitive
      haploid plantlets. Genetic crossing analysis of one of the transformed plants
      revealed the presence of one dominant trait for kanamycin resistance segregating
      in a Mendelian fashion in the F(1) generation.

PMID- 16453574
TI  - Isolation of a dual plant promoter fragment from the Ti plasmid of Agrobacterium
      tumefaciens.
AB  - The two most abundant transcripts derived from TR-DNA within plant cells
      transformed by an octopine strain of Agrobacterium tumefaciens arise from
      divergent transcription, both originating within an 500 bp section of the T-DNA.
      Using a combination of subcloning and exonuclease digestion, a 479-bp DNA
      fragment, directly flanked by the initiation codons for the two adjacent open
      reading frames, was isolated. The resulting DNA fragment was fused, in both
      orientations, to the neomycin phosphotransferase (NPT II) gene of the transposon
      Tn5 prior to introduction into Nicotiana tabacum cells via the Ti plasmid. The
      intergenic fragment was found to initiate expression of the NPT II gene in either
      orientation as assayed by kanamycin resistance of the transformed plant tissue as
      well as by enzymatic assay of the NPT II gene product. The plasmids described
      here are potential selection-expression vectors for plant systems.

PMID- 16453575
TI  - Initiation of translation of the cauliflower mosaic virus genome from a
      polycistronic mRNA: evidence from deletion mutagenesis.
AB  - Mutants with deletions in the open reading frame (ORF) VII to I region of the
      cauliflower mosaic virus genome were constructed in vitro and tested for
      infectivity by inoculation of plants. Sequences within ORF VII and the
      intergenomic region between ORFs VII and I are not required for viral
      infectivity. Nevertheless, the location of translation initiation and termination
      codons within this region governs the infectivity of the virus. Firstly,
      translation beginning at the initiation codon of ORF VII should reach an in-phase
      termination codon before the initiation codon of ORF I. Secondly, an initiation
      codon should be located in the vicinity of the sequence homologous to methionine
      tRNA, the proposed primer binding site for reverse transcription. Results suggest
      translation from a polycistronic mRNA by a ;relay race' mechanism whereby
      ribosomes after passing a termination codon re-initiate protein synthesis at the
      nearest AUG codon.

PMID- 16453576
TI  - A site-specific mutation within the active site of ribulose-1,5-bisphosphate
      carboxylase of Rhodospirillum rubrum.
AB  - In vitro mutagenic techniques have generated an asp-->glu substitution at residue
      198 adjacent to the carbamate-divalent metal ion binding site of Rhodospirillum
      rubrum ribulose 1,5-bisphosphate carboxylase. A single C-->A nucleotide change in
      the coding strand created the mutant and introduced a new EcoRI restriction site
      on the expression plasmid pRR2119. Although the carboxylase:oxygenase ratio
      remained the same, the mutant enzyme had slightly altered kinetic properties. The
      e.p.r. spectra of the quaternary complexes enzyme.activator carbamate.Mn.2
      carboxyarabinitol 1,5-bisphosphate and enzyme.activator carbamate.Mn.4
      carboxyarabinitol 1,5-bisphosphate for mutant and wild-type enzymes were
      different, indicating that the metal ion was in a slightly altered environment.
      These findings are consistent with the hypothesis that, besides the carbamate at
      lys 201, the carboxyl group of asp 198 contributes to the formation of the
      divalent metal ion binding site.

PMID- 16453577
TI  - Structure and chromosomal arrangement of leghemoglobin genes in kidney bean
      suggest divergence in soybean leghemoglobin gene loci following
      tetraploidization.
AB  - We have determined the structure of one of the leghemoglobin (Lb) genes of
      Phaseolus vulgaris (kidney bean) and deduced the chromosomal arrangement of
      leghemoglobin genes by genomic hybridizations with Lb and two other sequences,
      each specific to the 5' or 3' region of the soybean leghemoglobin loci. By
      comparing this organization with two other species of legumes, Glycine max
      (soybean) and G. soja (wild soybean), a phylogeny of leghemoglobin gene loci was
      traced. The intragenic structure of the kidney bean leghemoglobin gene shows the
      same intron/exon arrangement as that of soybean leghemoglobin genes and extensive
      sequence homologies in both coding as well as 5' and 3' non-coding regions. The
      presence in the kidney bean genome of four leghemoglobin genes suggests that
      tandem duplications of a single primordial plant globin gene had occurred to
      generate four leghemoglobin genes in an ;Lb-locus' before Glycine and Phaseolus
      species diverged. Chromosome duplication by tetraploidization in Glycine
      generated two loci containing four genes each. A large deletion in one of the two
      four-gene loci in soybean resulted in the generation of the Lbc(2) locus
      containing two leghemoglobin genes, one functional and another pseudo (LbPsi(2)).
      This pseudogene, unlike that present on the main locus, is represented by only
      two and a half exons and appears to be truncated. The two other truncated genes
      (LbT(1) and LbT(2)) were probably generated similarly in the genome of Glycine
      spp. following tetraploidization before the divergence of G. max and G. soja.

PMID- 16453579
TI  - Lampbrush chromosome loop-specificity of transcript morphology in spermatocyte
      nuclei of Drosophila hydei.
AB  - The transcript morphology in the lampbrush chromosome loop pairs ;threads' and
      ;pseudonucleolus' of the Y chromosome in primary spermatocytes of Drosophila
      hydei has been investigated by the Miller spreading technique. Each loop pair
      carries giant transcripts with a secondary structure characteristic of the
      respective loop. The lengths of the transcribed regions are in the range 500-1500
      kb or even larger. The results of our experiments are discussed in the context of
      loop ultrastructure, molecular structure and loop function. The high degree of
      secondary structure may be required to assemble specifically loop-specific
      proteins.

PMID- 16453578
TI  - Chlamydomonas reinhardii gene for the 32 000 mol. wt. protein of photosystem II
      contains four large introns and is located entirely within the chloroplast
      inverted repeat.
AB  - The chloroplast psbA gene from the green unicellular alga Chlamydomonas
      reinhardii has been localized, cloned and sequenced. This gene codes for the
      rapidly-labeled 32-kd protein of photosystem II, also identified as as herbicide
      binding protein. Unlike psbA in higher plants which is found in the large single
      copy region of the chloroplast genome and is uninterrupted, psbA in C. reinhardii
      is located entirely within the inverted repeat, hence present in two identical
      copies per circular chloroplast genome, and contains four large introns. These
      introns range from 1.1 to 1.8 kb in size and fall into the category of Group I
      introns. Two of the introns contain open reading frames which are in-frame with
      the preceding exon sequences. We present the nucleotide sequence for the C.
      reinhardii psbA 5'-and 3' -flanking sequences, the coding region contained in
      five exons and the deduced amino acid sequence. The algal gene codes for a
      protein of 352 amino acid residues which is 95% homologous, excluding the last
      eight amino acid residues, with the higher plant protein.

PMID- 16453581
TI  - Note added in proof.

PMID- 16453580
TI  - Phosphate incorporation into secretory protein of Chironomus salivary glands
      occurs during translation.
AB  - The Balbiani rings (BR) in Chironomus salivary gland cells code for giant
      secretory proteins, the sp-I family. During normal growth conditions the
      phosphorylated proteins sp-Ia and sp-Ib are formed with most phosphate present as
      phosphoserine. We can show that most if not all incorporation of P into sp-I
      occurs in parallel with the incorporation of [S]-methionine in the giant
      polysomes that form sp-I and contain BR-derived mRNA. We suggest that the main
      function of phosphorylation of sp-Ia and sp-Ib is to provide charge
      neutralization of an excess of lysine and arginine residues and is therefore
      required during early stages of protein folding. This view is supported by the
      previous observation that glutamic (and aspartic) acid largely substitute for
      phosphoserine in a non-phosphorylated member of the sp-I family, sp-Ic, which is
      produced during phosphate starvation.

PMID- 16453582
TI  - Note added in proof.

PMID- 16453583
TI  - Note added in proof.

PMID- 16453584
TI  - Synthetic donor and acceptor splice sites function in an RNA polymerase B (II)
      transcription unit.
AB  - [This corrects the article on p. 2026 in vol. 3.].

PMID- 16453585
TI  - An Agrobacterium-transformed cell culture from the monocot Asparagus officinalis.
AB  - Cultured stem fragments from the monocotyledonous plant Asparagus officinalis
      infected by the oncogenic bacterium Agrobacterium tumefaciens developed tumorous
      proliferations. This tissue was propagated in vitro on hormone-free culture
      medium. The T-DNA-encoded markers nopaline and agrocinopine were unambiguously
      detected in these tissues. The data demonstrate that stable T-DNA transfer as
      well as expression of T-DNA genes is possible in at least some monocotyledonous
      plants. This opens new possibilities for plant genetic engineering using the Ti
      plasmid as a gene vector.

PMID- 16453586
TI  - The limited host range of an Agrobacterium tumefaciens strain extended by a
      cytokinin gene from a wide host range T-region.
AB  - The host range of Agrobacterium tumefaciens strain LBA649 (pTiAg57) is limited to
      grapevine and a few other plant species. Its host range was extended through the
      introduction of the T-region from the wide host range octopine plasmid pTiAch5.
      In contrast, R prime plasmids harboring the entire wide host range virulence
      region were unable to achieve this effect. Via site-directed mutagenesis a search
      was performed to identify the T-DNA genes which were responsible for the observed
      host range extension. Inactivation of one of the onc-genes (the cyt gene) was
      found to abolish the capacity of the T-region to extend the host range of LBA649.
      Therefore, we cloned the cyt gene into a disarmed T-region plant vector and used
      it in complementation studies with pTiAg57 via the binary vector strategy. We
      show that the mere presence of the cyt gene from a wide host range Ti plasmid is
      sufficient to extend the host range of LBA649 to certain plants. We conclude that
      the limited host range of LBA649 is not caused by a lack of recognition of plants
      but is mainly due to the absence or inactivity of a cyt gene in the T-region of
      pTiAg57.

PMID- 16453587
TI  - Note added in proof.

PMID- 16453588
TI  - Purified phytochrome influences in vitro transcription in rye nuclei.
AB  - Nuclei isolated from dark-grown seedlings of rye by Percoll density gradient
      centrifugation incorporate radioactive UTP into RNA. Transcription is reduced to
      50% by the addition of alpha-amanitin (5 mug/ml) and correspondingly a decrease
      of the label in the mRNA fraction is seen on agarose gels. Purified 124-kd
      phytochrome in its far-red absorbing form (P(fr)) increases the incorporation of
      labeled UTP by 40-70% above untreated controls, whereas pre-illumination with far
      red light or addition of alpha-amanitin prevents this effect. Nuclei isolated
      from light-grown seedlings show only an increase of 5% upon addition of P(fr).
      Other proteins such as bovine serum albumin or cytochrome c do not enhance the
      rate of transcription. We conclude that the accumulation of mRNA species is
      influenced by phytochrome in its P(fr) form.

PMID- 16453590
TI  - Note added in proof.

PMID- 16453589
TI  - Molecular lesions associated with white gene mutations induced by I-R hybrid
      dysgenesis in Drosophila melanogaster.
AB  - We have identified molecular lesions associated with six mutations, w and w, of
      the white gene of Drosophila melanogaster. These mutations arose in flies subject
      to I-R hybrid dysgenesis. Four of the mutations give rise to coloured eyes and
      are associated with insertions of 5.4-kb elements indistinguishable from the I
      factor controlling I-R dysgenesis. The insertion associated with w is at a site
      which, within the resolution of these experiments, is identical to that of two
      previously studied I factors. This appears to be a hot-spot for I factor
      insertion. We have compared the sites of these insertions with sequences
      complementary to white gene mRNA identified by Pirrotta and Brockl. The hot-spot
      is in the fourth intron. The insertion carried by w is either within, or just
      beyond, the last exon. The insertion carried by w is near the junction of the
      first exon and first intron. The w mutation is a derivative of w. It contains an
      insertion of I factor DNA within, or immediately adjacent to, the F-like element
      associated with w, and results in restoration of some eye colour. This insertion
      is just upstream of the start of the white mRNA. Mutations w and w are deletions
      removing mRNA coding sequences. Both determine a bleached white phenotype.

PMID- 16453591
TI  - Note added in proof.

PMID- 16453592
TI  - Localization of two phosphorylation sites adjacent to a region important for
      polymerization on the tail of Dictyostelium myosin.
AB  - Phosphorylation of the myosin heavy chains of Dictyostelium discoideum is known
      to be inhibited following chemotactic stimulation of the cells. Effects of
      dephosphorylation on the assembly of myosin and on its actin-activated ATPase
      activity raised the question of where the phosphorylated sites are located with
      respect to sites responsible for polymerization and actin binding. Using seven
      monoclonal antibodies the binding sites of which were mapped in the electron
      microscope, two phosphorylation sites, i.e., threonine residues that were
      phosphorylated by a kinase from D. discoideum, were localized by immunoblotting
      of chymotryptic fragments. Two of the antibodies bound to the terminal one fifth
      of the tail and recognized a phosphorylated chymotryptic fragment of 38 kd. The
      non-phosphorylated form and single and double phosphorylated forms of this
      fragment were separated by two-dimensional electrophoresis. Antibody labeling of
      lower mol. wt. polypeptides indicated that both phosphorylation sites were
      located at least 32 kd from the end of the tail. A non-phosphorylated fragment,
      that was insoluble at low ionic strength due to polymerization, proved to be an
      internal cleavage product of the tail. A segment of this fragment necessary for
      polymerization was mapped adjacent to the phosphorylation sites.

PMID- 16453593
TI  - Note added in proof.

PMID- 16453594
TI  - Note added in proof.

PMID- 16453596
TI  - Characterization of an amber mutation in the structural gene for ribosomal
      protein L15, which impairs the expression of the protein export gene, secY, in
      Escherichia coli.
AB  - [This corrects the article on p. 2323 in vol. 3.].

PMID- 16453595
TI  - Cloning of genes involved in pathogenicity of Xanthomonas campestris pv.
      campestris using the broad host range cosmid pLAFR1.
AB  - A genomic library was prepared in Escherichia coli from DNA of wild-type
      Xanthomonas campestris pv. campestris (aetiological agent of crucifer black rot),
      partially digested with endonuclease EcoRI, using the mobilisable broad host
      range cosmid vector pLAFR1. Recombinant plasmids contained inserts ranging in
      size from 19.1 to 32.3 kb (mean 26.6). Certain of the clones complemented E. coli
      auxotrophic markers. Using the narrow host range plasmid pRK2013 as a helper the
      pooled recombinant plasmids were transferred conjugally to X. c. campestris
      mutants, and clones were identified which restored yellow pigmentation to white
      mutants, prototrophy to amino acid auxotrophs and pathogenicity towards turnip
      plants to two non-pathogenic mutants. The lesion in one mutant (8288,
      complemented by the plasmid pIJ3000) is unknown. However mutant 8237 is defective
      in production of extracellular protease and polygalacturonate lyase and
      restoration of pathogenicity by complementation with the plasmid pIJ3020
      concomitantly restored both enzyme levels to wild-type values.

PMID- 16453597
TI  - Immunochemical characterization of wild-type and variant glucocorticoid receptors
      by monoclonal antibodies.
AB  - [This corrects the article on p. 1498 in vol. 3.].

PMID- 16453598
TI  - The hierarchical relation between X-chromosomes and autosomal sex determining
      genes in Drosophila.
AB  - The classical balance concept of sex determination in Drosophila states that the
      X-chromosome carries dispersed female-determining factors. Besides, a number of
      autosomal genes are known that, when mutant, transform chromosomal females (XX)
      into pseudomales (tra), or intersexes (ix, dsx, dsx). To test whether large
      duplications of the X-chromosome have a feminizing effect on the sexual phenotype
      of these mutants, we constructed flies that were mutant for ix, dsx, dsx or tra
      and had two X-chromosomes plus either a distal or a proximal half of an X
      chromosome. These or even smaller X-chromosomal fragments had a strong feminizing
      effect when added to triploid intersexes (XX; AAA). In the mutants, however, no
      shift towards femaleness was apparent. We conclude that enhancing the female
      determining signal is ineffective in flies that are mutant for an autosomal sex
      determining gene, and therefore, that these genes are under hierarchical control
      of the signal given by the X:A ratio. Parallels between sex-determining and
      homeotic genes are drawn.

PMID- 16453599
TI  - A transposable P vector that confers selectable G418 resistance to Drosophila
      larvae.
AB  - Drosophila larvae are rapidly killed by food containing the antibiotic G418. The
      bacterial gene for neomycin resistance introduced in the genome by P-mediated
      transformation renders larvae resistant to G418 and able to grow to fertile
      adults. The neo gene transcribed from the herpes thymidine kinase promoter gives
      low levels of resistance but high levels can be obtained using the hsp70 heat
      shock promoter. We have constructed a vector for P-mediated transformation which
      uses this finding to allow dominant selection of transformed progeny. Features of
      this vector also facilitate cloning and allow the rapid recovery of the inserted
      transposon from transformed flies. We have also constructed a cosmid vector for P
      mediated transformation that incorporates the hsp70-neo gene.

PMID- 16453600
TI  - Protein-chemical characterization of NF-H, the largest mammalian neurofilament
      component; intermediate filament-type sequences followed by a unique carboxy
      terminal extension.
AB  - NF-H has the highest mol. wt. of the three mammalian neurofilament components (NF
      L, NF-M, NF-H). In spite of its unusually large mol. wt., estimated to be 200 K
      by gel electrophoresis, NF-H contains sequences which identify it as an integral
      intermediate filament (IF) protein in its amino-terminal region. We have isolated
      and partially characterized a basic, non-alpha-helical segment located at the
      amino-terminal end with properties similar to headpieces of other non-epithelial
      IF proteins. The highly alpha-helical 40-K fragment excised by chymotrypsin is
      now identified by the amino acid sequence of a 17-K fragment. This sequence can
      be unambiguously aligned with the rod region of other IF proteins and covers
      about half of the presumptive coiled-coil arrays. NF-H and NF-M show 45% sequence
      identity in this region. The extra mass of NF-H in comparison with most other IF
      proteins arises from a carboxy-terminal extension thought to be responsible for
      inter-neurofilament cross-bridges in axons. This autonomous domain has a unique
      amino acid composition characterized by a high content of proline, alanine and
      particularly of lysine and glutamic acid. The NF-H tailpiece extension also
      carries a large number of serine phosphates, which are not evenly distributed,
      but are restricted to the amino-terminal part. Having now delineated the
      intermediate filament-type sequences for all three neurofilament proteins it
      seems very likely that the three components interact via coiled-coil
      interactions. They all carry unique carboxy-terminal extensions which increase in
      length from NF-L to NF-H and seem to extend from the filament wall.

PMID- 16453601
TI  - Electron microscopy of the conformational changes of alpha 2-macroglobulin from
      human plasma.
AB  - High resolution electron microscopy reveals that fully active alpha 2
      macroglobulin (alpha2M) from fresh human plasma presents a very characteristic
      tetrameric structure. This native conformation of the alpha2M molecule is
      described here for the first time, along with its various orientations in
      negatively stained preparations. Although the native form is sensitive to
      inactivation, glutaraldehyde fixation is not necessary for its observation except
      when ammonium salts are used. The tetrameric structure of alpha2M undergoes a
      drastic conformational change when the protein is treated either with trypsin,
      thrombin or methylamine, as evidenced by the appearance of the
      typical)+(structure already described in the literature. The various aspects of
      this second conformation correspond to different orientations of the molecules in
      the stain film, and depend upon the nature of the support.

PMID- 16453603
TI  - New cloning vehicles for transformation of higher plants.
AB  - We have constructed a set of small vectors based on the tumor-inducing (Ti)
      plasmid of Agrobacterium tumefaciens which allow the transfer of exogenous DNA
      into plant chromosomes. These vectors contain: (i) a chimeric gene containing the
      transcriptional control signals from the nopaline synthase gene and the coding
      sequence for neomycin phosphotransferase; (ii) the ColE1 replicon; (iii) the cos
      site of bacteriophage lambda; (iv) the border sequences from the ends of the T
      DNA region of the Ti plasmid; and (v) a wide host range replicon. Due to the
      small size of these cosmid vectors, DNA fragments up to 35 kbp can be inserted by
      an in vitro packaging method in Escherichia coli. The ability of these vectors to
      be stably replicated in both E. coli and A. tumefaciens allows their subsequent
      transfer to and maintenance in Agrobacterium without intermediate genetic
      manipulations. We demonstrate that DNA cloned into these vectors in A.
      tumefaciens can efficiently transform plants when in trans with a wild-type Ti
      plasmid which donates the functions necessary for DNA transfer and integration.
      We also show that only the right border of the T-DNA is necessary for DNA
      transformation.

PMID- 16453604
TI  - Co-ordinated synthesis of phytoalexin biosynthetic enzymes in biologically
      stressed cells of bean (Phaseolus vulgaris L.).
AB  - Changes in the rates of synthesis of three enzymes of phenyl-propanoid
      biosynthesis in Phaseolus vulgaris L. (dwarf French bean) have been investigated
      by immunoprecipitation of [S]methionine-labeled enzyme subunits with mono
      specific antisera. Elicitor causes marked, rapid but transient co-ordinated
      increases in the rate of synthesis of phenyl-alanine ammonia-lyase, chalcone
      synthase and chalcone isomerase concomitant with the phase of rapid increase in
      enzyme activity at the onset of accumulation of phenyl-propanoid-derived
      phytoalexin antibiotics in suspension cultures of P. vulgaris. Co-ordinate
      induction of enzyme synthesis is also observed in hypocotyl tissue during
      race:cultivar-specific interactions with Colletotrichum lindemuthianum, causal
      agent of anthracnose. In an incompatible interaction (host resistant) there are
      early increases apparently localized to the initial site of infection prior to
      the onset of phytoalexin accumulation and expression of hypersensitive
      resistance. In contrast, in a compatible interaction (host susceptible) there is
      no induction of synthesis in the early stages of infection, but a delayed
      widespread response at the onset of lesion formation associated with attempted
      lesion limitation. It is concluded that expression of the phytoalexin defense
      response in biologically stressed cells of P. vulgaris characteristically
      involves co-ordinate induction of synthesis of phytoalexin biosynthetic enzymes.

PMID- 16453605
TI  - Control of psbA gene expression: in mature Spirodela chloroplasts light
      regulation of 32-kd protein synthesis is independent of transcript level.
AB  - Spirodela oligorrhiza plants were used to study direct effects of light on
      plastid gene expression uncoupled from sequential chloroplast-developmental
      processes. Specific transcript levels were analysed using chloroplast, gene
      fragment probes. Protein synthesis in vivo and in vitro was also measured. In
      tissue with mature chloroplasts, light/dark regimes had no substantial effect on
      transcript levels of the psbA gene coding for the 32-kd protein. However, under
      the same conditions, synthesis of the protein itself was dramatically affected.
      We conclude that in mature chloroplasts synthesis of 32-kd protein is regulated
      mainly at a translational level. Transcript levels of the rbcL gene, coding for
      the large subunit of ribulosebisphosphate carboxylase-oxygenase, were somewhat
      sensitive to light/dark effects, although not to the same degree as was synthesis
      of the protein. We conclude that translational events and transcript levels are
      involved in regulating synthesis of this polypeptide. Carbon deprivation in the
      dark reduced psbA and rbcL transcript levels appreciably below those found in non
      starved, dark-grown tissue. This suggests that starvation and dark effects must
      be experimentally separated from each other for valid conclusions to be drawn
      about light/dark regulation of chloroplast gene expression.

PMID- 16453606
TI  - Molecular cloning of Erwinia chrysanthemi pectinase and cellulase structural
      genes.
AB  - Erwinia chrysanthemi 3937 secretes four major pectate lyase isoenzymes (PL, EC
      4.2.2.2) and one endocellulase (Cx, EC 3.2.1.4). A genomic library of this strain
      was constructed in the Lambda L47-1 vector, and screened for the presence of PL
      and Cx on pectate and caboxymethylcellulose agar. Among the seven Cx-positive
      phage clones, three were shown to encode an enzyme of the same mol. wt. as the
      one found in the culture supernatant of strain 3937. The 34 PL-positive phage
      clones were analyzed by electrofocusing and could, according to the PL they
      produced, be arranged in five classes. Phages from three classes produced three
      different single PL, named PLb, c and d. No common fragment was evidenced between
      the inserts of the phages of these three classes. This demonstrated that, in
      strain 3937, PLb, C, and d were encoded by three different genes called pelB, C,
      and D. Furthermore, our results suggest the existence of two additional genes
      encoding PLa and e. In addition, a pectin methylesterase gene was found closely
      linked to pelD.

PMID- 16453607
TI  - In vivo cloning of the pectate lyase and cellulase genes of Erwinia chrysanthemi.
AB  - Using an RP4 plasmid which carries a mini-Mu prophage which allows it to
      integrate spontaneously random pieces of its host chromosome, we cloned in vivo
      at least some of the pectate lyase and cellulase genes of the Erwinia
      chrysanthemi strain B374. The RP4-prime plasmids were used to localize the cloned
      genes on the B374 chromosome by co-transposition mapping and to subclone most of
      the genes in a classic high copy number plasmid vector.

PMID- 16453609
TI  - Each zein gene class can produce polypeptides of different sizes.
AB  - The family of zein proteins in maize consists of several prototypes whose amino
      sequence is characterized by a repetitive block structure. We have now isolated
      and characterized a new series of zein cDNA clones from a cDNA library made from
      protein-body polysomal mRNA. The nucleotide sequences and the hybrid-selected
      translation results indicate that anomalous zein genes with termination codons
      within the coding region are transcribed, translated and possibly accumulated
      into zein protein bodies. The sequence analysis of these new clones and their
      comparison with already characterized zein sequences, all from the same maize
      line, indicate a large variability in the amino acid sequence of the blocks both
      among the prototypes and within members of each prototype. Northern blot analysis
      of total RNA from endosperms at different maturation stages shows a differential
      expression of each prototype sequence with the production, within each family, of
      zein transcripts coding for discrete size classes of polypeptides. The results
      allow a better definition of the zein system, clarify the relationship between
      sequence types and polypeptide size classes, and suggest the possibility of
      inserting lysine codons to raise the nutritional value of the seed storage
      protein.

PMID- 16453608
TI  - Cloning of the extra sex combs gene of Drosophila and its identification by P
      element-mediated gene transfer.
AB  - A large region containing the extra sex combs (esc) gene of Drosophila has been
      cloned by microdissection from polytene chromosomes and chromosomal walking.
      Within this DNA, the segment comprising the esc gene has been narrowed down in
      several steps. First, a deletion of the esc gene, Df(2L)esc, defined a region of
      380 kb. Then, a duplication carrying the esc gene, Dp(2;2)GYL, and a deletion not
      eliminating esc, Df(2L)prd, further reduced this region to 160 kb. Finally,
      because esc transcripts are expected to be present in follicles but absent in
      adult males, mapping of follicle and adult male transcripts limited the esc
      region to 10 kb. Rigorous proof that this DNA contained the esc gene was obtained
      by P-element-mediated transformation. We conclude that the 12 kb of DNA used for
      transformation include the esc gene as well as all flanking sequences required
      for its proper regulation in the female germ line.

PMID- 16453610
TI  - Thermo-induced transcripts of a soybean heat shock gene after transfer into
      sunflower using a Ti plasmid vector.
AB  - A genomic DNA fragment containing a soybean heat shock gene (hs6871) was inserted
      into the T-DNA region of the Agrobacterium tumefaciens pTiC58 plasmid. A strain
      carrying the modified Ti plasmid was used to incite tumors in sunflower
      hypocotyls. The expression of the heat shock gene was investigated by Northern
      blot analysis of RNA and S1 nuclease mapping of the transcriptional start site.
      Heat shock-induced poly(A) mRNA was detected in tumor tissue only after
      incubation at 40 degrees C (heat shock) not at the normal growth temperature (28
      degrees C). Transcripts from hs6871 are faithfully initiated in sunflower,
      starting at the same site on the DNA as in soybean. The low level of transcripts
      initiating correctly on hs6871 in sunflower is consistent with a general tissue
      specific reduction in the expression of partially homologous native heat shock
      genes in sunflower tumors.

PMID- 16453611
TI  - Nucleotide sequence of the S-1 mitochondrial DNA from the S cytoplasm of maize.
AB  - Mitochondria from the S male-sterile cytoplasm of maize contain unique DNA
      protein complexes, designated S-1 and S-2. These complexes consist of double
      stranded linear DNAs with proteins covalently attached to the 5' termini. To
      learn more about these unusual DNAs we have determined the complete nucleotide
      sequence of the S-1 DNA molecule (6397 bp). The sequence of S-2 has been
      previously determined. S-1 and S-2 are structurally similar and contain 1.7kb of
      sequence homology. S-1 is terminated by exact 208-bp inverted repeats that are
      identical with the terminal inverted repeats of S-2. S-1 and S-2 also contain a
      1462-bp region of nearly perfect homology, which includes one of the terminal
      inverted repeats. The homology between the two molecules may be maintained, in
      part, by homologous recombination. S-1 has three long unidentified open reading
      frames, URF2 (1017 bp), URF3 (2787 bp) and URF4 (768 bp). URF2 occurs in the 1462
      bp region of homology and is identical in length and location in both S-1 and S
      2. Based on their structural organization and their viral-like characteristics,
      we propose that S-1 and S-2 code for functions involved with their maintenance
      and replication.

PMID- 16453612
TI  - In vivo acylation of Dictyostelium actin with palmitic acid.
AB  - Cells of Dictyostelium discoideum were incubated with [H]palmitic acid during
      development, and recovery of the fatty acid label in soluble and membrane
      associated proteins was investigated. One of the major labeled proteins was found
      exclusively in the soluble fraction. This protein, with an apparent mol. wt. of
      44 kd, was identified as actin based on its labeling with a monoclonal anti-actin
      antibody, its coincidence with the major [S]methionine-labeled protein after two
      dimensional electrophoresis and its binding to a DNase I affinity column. The H
      label was resistant to chloroform-methanol extraction and boiling in SDS
      containing buffer. After partial purification by preparative SDS-polyacrylamide
      gel electrophoresis, the 44-kd protein was treated with KOH, the fatty acids
      released were derivatized to methyl esters and palmitic acid methylester was
      identified by gas-liquid chromatography.

PMID- 16453613
TI  - A major part of the polypeptide chain of tobacco mosaic virus protein is
      antigenic.
AB  - Eighteen synthetic peptides representing virtually the entire length of the
      polypeptide chain of tobacco mosaic virus coat protein (TMVP) have been analyzed
      for their ability to bind in an enzyme immunoassay to 30 monoclonal antibodies
      raised against the dissociated viral subunits. Only five of the monoclonal
      antibodies were able to bind a number of peptides while the other 25 antibodies
      recognized only the complete molecule and seemed to be specific for
      conformational features that are absent in the peptide fragments. The 18 peptides
      were also tested for their ability to bind to several antisera to TMVP. Virtually
      the entire sequence of TMVP possessed antigenic activity. Four new epitopes were
      identified in the vicinity of residues 19-32, 90-95, 115-134 and 134-146. These
      results bring to 11 the number of continuous epitopes that have been identified
      in the TMVP molecule and show that the entire surface of the molecule is
      antigenic. When peptides of TMVP of a length of 6-8 residues were tested for
      antigenic activity previously a correlation was found between the location of
      short continuous epitopes and mobile segments of the protein. In the present
      study, in which longer peptides as well as monoclonal antibodies were used to
      probe the antigenicity of TMVP, additional conformation-dependent epitopes were
      shown to be present. Our results illustrate the operational nature of any
      definition of antigenicity and caution against the use of any single criterion
      for distinguishing between antigenic and non-antigenic regions of a protein.

PMID- 16453614
TI  - Chloroplast transformation by Agrobacterium tumefaciens.
AB  - A chimeric gene consisting of the promoter region of the nopaline synthase gene
      (Pnos) fused to the coding sequence of the chloramphenicol acetyltransferase gene
      (cat gene) of Tn9 was introduced by co-cultivation in tobacco protoplasts
      followed by selection with 10 mug/ml chloramphenicol. The chloramphenicol
      resistant plants derived from these selected calli were unable to transmit the Cm
      phenotype through pollen. A typically maternal inheritance pattern was observed.
      Southern blot analysis showed that the chimeric Pnos-cat gene was present in the
      chloroplasts of these resistant plants. Furthermore, the chloramphenicol
      acetyltransferase activity was shown to be associated with the chloroplast
      fraction. These observations are the first proof that the Agrobacterium Ti
      plasmid vectors can be used to introduce genes in chloroplasts.

PMID- 16453615
TI  - Structure of the sucrose synthase gene on chromosome 9 of Zea mays L.
AB  - The structure of the shrunken gene of Zea mays encoding sucrose synthase (EC
      2.4.1.13) was determined by (i) sequencing the transcription unit and 1.2 kb of
      5' -upstream sequences from a genomic clone, (ii) by sequencing a nearly full
      length cDNA clone and (iii) by determining the transcription start site by a
      combination of primer extension experiments with synthetic oligodeoxynucleotide
      primers and S1 mapping. The sucrose synthase gene is 5.4 kb long, of which 2746
      bp are found in the mature mRNA. The gene is interrupted by 15 introns. The first
      two introns are 1 kb and 0.5 kb in length, respectively, while the other introns
      are much smaller. A TATA box is located 30 bp upstream from the transcription
      start site. Approximately 610 bp upstream of the transcription start site a
      direct repeat of 16 nucleotides, separated by a 4-fold repetition of the sequence
      GGTGG is detected. The 16-bp sequence has similarities to a sequence repeat found
      between two promoters of a maize zein gene also expressed in the endosperm
      tissue. The transposable element Ds in the mutant sh-m5933 and sh-m6233 alleles
      is inserted in the seventh and first intron, respectively. The genomic and cDNA
      clones were obtained from different maize lines. This allows the determination of
      polymorphic sites which are frequent in 3rd codon position and absent in 1st and
      2nd codon positions. In addition, the 3' -untranslated sequence shows two
      duplications that may have arisen by the insertion and subsequent excision of
      transposable elements.

PMID- 16453616
TI  - The wheat chloroplast gene for CF(0) subunit I of ATP synthase contains a large
      intron.
AB  - The gene for CF(0) subunit I of ATP synthase has been located in wheat
      chloroplast DNA, between the genes for CF(0) subunit III and alpha subunit of
      CF(1). Nucleotide sequencing and analysis of RNA-DNA hybrids indicated that the
      gene is interrupted by an 823-bp intron which has boundaries similar to those
      previously described for the introns in protein-coding chloroplast genes of
      Euglena gracilis. The deduced amino acid sequence of CF(0) subunit I indicates a
      polypeptide of 183 amino acid residues. However, N-terminal amino acid sequencing
      of the mature spinach CF(0) subunit I suggests that the protein is synthesised
      with a N-terminal extension of 17 amino acid residues and is processed to give a
      protein of mol. wt. 19 001 of 166 amino acids residues. The mature CF(0) subunit
      I shows similarities in primary and predicted secondary structure to F(0) subunit
      b of Escherichia coli ATP synthase. A major transcript of 3.3 kb containing
      sequences from the genes for CF(0) subunit III, subunit I and CF(1) subunit alpha
      has been observed by RNA-DNA hybridisation.

PMID- 16453617
TI  - The maize cytochrome c oxidase subunit I gene: sequence, expression and
      rearrangement in cytoplasmic male sterile plants.
AB  - The single copy of the gene for cytochrome c oxidase subunit I (COX I) present in
      the mitochondrial genome of fertile maize (Zea mays L.) is encoded by a
      continuous open reading frame of 1584 nucleotides. The predicted polypeptide
      encoded by the gene has a mol. wt. of 58 219 daltons and shows >60% amino acid
      sequence homology with the corresponding fungal and animal polypeptides. Two
      major transcripts of 2400 and 2300 nucleotides can be detected and the 5' end of
      the larger transcript maps to a sequence from -161 to -153 (relative to the
      initiator codon) which shows high homology to the yeast mitochondrial promoter.
      In mitochondrial DNA from the S male-sterile cytoplasm of maize, which also
      characteristically contain two low mol. wt. linear DNAs (S1 and S2),
      rearrangements just 5' (at -175) to the COX I gene, generate additional DNA
      restriction fragments containing entire copies of the gene. These rearrangements
      involve a sequence identical to the terminal 186 bp of the 208-bp inverted repeat
      sequence found at either end of the S1 and S2 DNAs.

PMID- 16453618
TI  - Molecular analysis of instability in flower pigmentation of Antirrhinum majus,
      following isolation of the pallida locus by transposon tagging.
AB  - The pal locus of Antirrhinum majus was cloned using the transposable element, Tam
      3, as a probe. The pal clone was used to examine, at the molecular level, those
      aspects of instability previously observed phenotypically and genetically. The
      effects of temperature and of genetic background on excision of the element at
      pal are considered, and related quantitatively to the phenotype. We describe the
      identification of the transcript of the pal locus and show that insertion of Tam
      3 blocks the production of a normal pal transcript in developing flower buds.

PMID- 16453619
TI  - Hormonal regulation of beta1,3-glucanase messenger RNA levels in cultured tobacco
      tissues.
AB  - We describe the isolation of a cDNA clone of beta1,3-glucanase mRNA from
      Nicotiana tabacum L. cv. ;Havana 425' and its use to measure the kinetics of mRNA
      accumulation in cultured tobacco tissues treated with the plant hormones auxin
      and cytokinin. Northern blot analysis showed that the tissues contain a single
      1.6 kb-sized beta1,3-glucanase mRNA. The levels of beta1,3-glucanase and beta1,3
      glucanase mRNA increase by up to seven- and 20-fold, respectively, over a 7-day
      period in tissues subcultured on hormone-free medium and medium containing auxin
      or cytokinin added separately. Over the same interval of time, the content of
      both the enzyme and its mRNA remains at a constant low level in tissues
      subcultured on medium containing both auxin and cytokinin. The results show that
      auxin and cytokinin block beta1,3-glucanase production at the level of the mRNA.

PMID- 16453620
TI  - Nuclear mutation leads to an accelerated turnover of chloroplast-encoded 48 kd
      and 34.5 kd polypeptides in thylakoids lacking photosystem II.
AB  - We have studied the synthesis and accumulation of a chloroplast-encoded 48 kd
      chla-reaction center protein and the 34.5 kd ;atrazine binding' protein in a
      nuclear maize mutant which fails to assemble photosystem II reaction centers. The
      failure of these polypeptides to accumulation in mutant thylakoids is not due to
      direct nuclear control over their synthesis but is rather due to their specific,
      accelerated turnover from the thylakoid membrane. The accelerated turnover of
      these polypeptides in mutant thylakoids is largely independent of illumination
      conditions, as accelerated turnover occurs in the dark as well as in the light.
      In contrast to wild type, the 48 kd and 34.5 kd polypeptides are preferentially
      associated with stroma, rather than grana, lamellae in mutant membranes,
      suggesting that turnover occurs before these polypeptides become enriched in the
      grana. The nucleus thus plays a role in the stabilization of these chloroplast
      encoded photosystem II reaction center polypeptides.

PMID- 16453621
TI  - Light-dependent degradation of the Q(B)-protein in isolated pea thylakoids.
AB  - The 32 000-dalton Q(B)-protein of photosystem II (PS II) is rapidly damaged and
      removed from isolated pea thylakoids during incubation in the light resulting in
      a loss of photosynthetic electron flow through PS II. This in vitro
      photoinhibition is similar to that previously reported with intact Chlamydomonas
      cells. The damage occurs at a faster rate in vitro, however, due to the inability
      of isolated thylakoids to synthesize replacement Q(B)-protein. The removal of the
      damaged Q(B)-protein does not require any soluble components of the chloroplast
      stroma and is unaffected by the protease inhibitors phenyl-methylsulfonylfluoride
      or antipain. Unlike the effect of trypsin, no low mol. wt. membrane-bound or
      soluble fragments of the labelled Q(B)-protein could be identified either by
      autoradiography or immunologically using polyclonal antibodies specific for the
      Q(B)-protein. The lightinduced damage to the Q(B)-protein (indicated by a loss of
      Q(B) functional activity), preceded the removal of the protein from the membrane.
      We conclude that photodamage of the Q(B)-protein generates a conformational
      change which renders the protein susceptible to attack by a highly efficient,
      intrinsic membrane protease.

PMID- 16453622
TI  - Polypeptides of DNA-dependent RNA polymerase of spinach chloroplasts:
      characterization by antibody-linked polymerase assay and determination of sites
      of synthesis.
AB  - Using solid-phase ;Sandwich' immunoassays we studied DNA-dependent RNA polymerase
      of spinach chloroplasts with regard to (i) polypeptide composition of the
      multimeric enzyme; (ii) immunological cross-reaction with Escherichia coli RNA
      polymerase; (iii) sites of synthesis of polymerase polypeptides. Our main results
      are as follows. (i) All polypeptides of isolated chloroplast RNA polymerase (150,
      145, 110, 102, 80, 75 and 38 kd) are labeled by an antibody-linked polymerase
      assay (ALPA), i.e., they are immunologically related to subunits of the
      holoenzyme. On the other hand differences in the patterns of ;ALPA-reactive'
      polypeptides of a crude RNA polymerase fraction and of the purified enzyme
      preparation indicate partial proteolytic degradation of polymerase polypeptides
      during purification. Thus the 80- and 75-kd polypeptides, which had been
      previously considered as true RNA polymerase polypeptides, probably result from
      partial proteolytic degradation. (ii) The 150- and 145-kd polypeptides show
      immunochemical similarities with the beta and/orbeta' subunits of E. coli RNA
      polymerase. (iii) Results from solidphase immunoassay of in vitro translated
      products of both chloroplast RNA and poly(A) (nuclear) RNA suggest that all
      chloroplast RNA polymerase polypeptides are coded for by the nucleus.

PMID- 16453623
TI  - The ;heavy' subunit of the photosynthetic reaction centre from Rhodopseudomonas
      viridis: isolation of the gene, nucleotide and amino acid sequence.
AB  - The gene coding for the ;heavy' subunit of the photosynthetic reaction centre
      from Rhodopseudomonas viridis was isolated in an expression vector. Expression of
      the heavy subunit in Escherichia coli was detected with antibodies raised against
      crystalline reaction centres. The entire subunit, and not a fusion protein, was
      expressed in E. coli. The protein coding region of the gene was sequenced and the
      amino acid sequence derived. Part of the amino acid sequence was confirmed by
      chemical sequence analysis of the protein. The heavy subunit consists of 258
      amino acids and its mol. wt. is 28 345. It possesses one membrane-spanning alpha
      helical segment, as was revealed by the concomitant X-ray structure analysis.

PMID- 16453624
TI  - Site-specific deletion in cauliflower mosaic virus DNA: possible involvement of
      RNA splicing and reverse transcription.
AB  - A frequent site-specific deletion was observed in the life cycle of cauliflower
      mosaic virus (S strain). Analysis of the sequence around the deletion site and
      the parental sequence implied that the deletion was promoted at sequences similar
      to the donor and acceptor consensus sequences of RNA splicing, designated as the
      deletion donor and acceptor sequences, respectively. To elucidate the mechanism
      of this site-specific deletion, point mutations were introduced into the deletion
      donor sequence (GT to GG or GA transversion). Deletion at the original deletion
      donor site did not occur in these mutants, instead, new (cryptic) donor sites
      were activated. All of these activated cryptic sites had sequences similar to the
      splicing consensus sequence. In all cases except one, the original deletion
      acceptor site was used. These results can be most readily explained by
      postulating that the site-specific deletion occurs by reverse transcription of
      spliced viral RNA. This frequent site-specific deletion was not observed in other
      strains. For a virus which replicates by reverse transcription, a mechanism to
      regulate the rate of splicing is required to ensure the intactness of the viral
      genome. We discuss the possibility that the S strain has a mutation in this
      regulatory mechanism.

PMID- 16453625
TI  - Actin gene mutations in Drosophila; heat shock activation in the indirect flight
      muscles.
AB  - We have identified four mutations affecting the actin III isoform in the indirect
      flight muscles (IFM) of Drosophila. One mutation does not produce any protein
      product, and three direct the synthesis of electrophoretic variants of actin.
      Complementation tests and recombination mapping indicate that all mutations are
      alleles of an actin gene at chromosomal band 88F (act88F gene). The effect of
      these mutations is restricted to the IFM. We conclude that the act88F gene is
      expressed only in the IFM to encode actin III, which is its major isoform. In two
      of the actin mutants, heat shock proteins are constitutively expressed in the
      IFM. Genetic evidence strongly suggest that this anomaly is primarily caused by
      the mutations in the act88F structural gene.

PMID- 16453626
TI  - The distribution of Ultrabithorax transcripts in Drosophila embryos.
AB  - We have used in situ hybridization to monitor the distribution of Ultrabithorax
      (Ubx) transcripts during the early stages of Drosophila embryogenesis. When first
      detectable, in the late syncytial blastoderm, Ubx transcripts are broadly
      distributed from 20 to 50% egg length (measured from the posterior pole). By the
      completion of cellular blastoderm formation, a precisely bounded zone one segment
      wide is defined by the accumulation of high levels of Ubx transcripts. This zone
      is probably the primordium for parasegment 6, that is, the posterior compartment
      of the third thoracic segment (T3) and the anterior compartment of the first
      abdominal segment (A1). Following gastrulation, seven metameric units of the germ
      band express Ubx transcripts in most or all cells of both the ectoderm and the
      mesoderm. This principal domain of Ubx expression is sharply bounded at
      superficial grooves in the embryo which probably mark the A/P compartment
      boundaries in T3 and A7, and so consists of parasegments 6-12. Outside this
      region, Ubx transcripts can be detected in only a few cells of the ectoderm of
      parasegments 5 and 13, and in the amnioserosa. This distribution suggests that
      the major role of Ubx in the early embryo lies in the morphological domain
      generally ascribed to the control of the bithoraxoid gene. Later in
      embryogenesis, the pattern of Ubx transcript accumulation is different in each of
      the major germ layers, suggesting that different controls regulate Ubx in each.
      In the ectoderm, but not in the mesoderm, Ubx transcripts accumulate
      differentially in anterior and posterior compartments. Probes prepared from
      different regions of the Ubx transcription unit show related but different
      patterns of hybridization. These patterns suggest that the 3.2-kb Ubx transcript
      is distributed throughout the wider domain of Ubx expression, but that the 4.7-kb
      transcript accumulates preferentially in parasegment 6.

PMID- 16453627
TI  - Transition stages of molecular drive in multiple-copy DNA families in Drosophila.
AB  - Multigene and non-genic DNA families are in a state of turnover and hence are
      continually being replaced throughout a population by new variant repeats. To
      quantify such molecular processes, in the absence of selection, it is necessary
      to find and compare stages of transistion during the homogenization of at least
      two non-genic families evolving in parallel in a closely related group of
      species. Detailed sequence analysis of patterns of variation, at each nucleotide
      position considered independently, amongst repeats of two tandem DNA families
      from seven related Drosophila species, reveals all stages of transition during
      the spread of randomly produced variant repeats. Variant repeats are found at
      different stages of homogenization and fixation in a population, irrespective of
      the loci, chromosomes or individuals from which they were cloned. Differences
      between the families in the relatively small number of variants at each
      transition stage and the greater number of fully homogenized and fixed variants
      between species of greater divergence indicate that the process of spread
      (molecular drive) is rapid relative to the mutation rate and occurs at seemingly
      different constant rates for each family. Occasional gene conversions, in
      addition to unequal exchanges, have contributed to family turnover. The
      significance of these results to the evolution of functional multigene families
      and divergence and conservation of sequences is discussed.

PMID- 16453628
TI  - Synthesis, transport and localization of a nuclear coded 22-kd heat-shock protein
      in the chloroplast membranes of peas and Chlamydomonas reinhardi.
AB  - The synthesis, transport and localization of a nuclear coded 22-kd heat-shock
      protein (HSP) in the chloroplast membranes was studied in pea plants and
      Chlamydomonas reinhardi. HSPs were detected in both systems by in vivo labeling
      and in vitro translation of poly(A)RNA, using the wheat-germ and reticulocyte
      lysate systems. Heat-shock treatment of pea plants for 2 h at 42-45 degrees C
      induces the expression of 10 nuclear coded proteins, among which several (18 kd,
      19 kd, 22 kd) are predominant. A 22-kd protein is synthesized as a 26-kd
      precursor protein and is localized in a chloroplast membrane fraction in vivo.
      Following post-translational transport into intact chloroplasts in vitro of the
      26-kd precursor, the protein is processed but the resulting 22-kd mature protein
      is localized in the chloroplast stroma. If, however, the in vitro transport is
      carried out with chloroplasts from heat-shocked plants, the 22-kd protein is
      preferentially transported to the chloroplast membrane fraction. In C. reinhardi
      the synthesis of poly(A)RNAs coding for several HSPs is progressively and
      sequentially induced when raising the temperature for 1.5 h from 36 degrees C to
      42 degrees C, while that of several preexisting RNAs is reduced. Various pre
      existing poly(A)RNAs endure in the cells at 42 degrees C up to 5 h but are no
      longer translated in vivo, whereas some poly(A)RNAs persist and are translated.
      As in pea, a poly(A)RNA coded 22-kd HSP is localized in the chloroplast membranes
      in vivo, although it is translated as a 22-kd protein in vitro. The in vitro
      translated protein is not transported in isolated pea chloroplast which, however,
      processes and transports other nuclear coded chloroplast proteins of
      Chlamydomonas. The poly(A)RNA coding for the 22-kd HSP appears after 1 h at 36
      degrees C. Its synthesis increases with the temperature of incubation up to 42
      degrees C, although it decreases after 2 h of heat treatment and the already
      synthesized RNA is rapidly degraded. The degradation is faster upon return of the
      cells to 26 degrees C. None of the heat-induced proteins is identical to the
      light-inducible proteins of the chloroplast membranes.

PMID- 16453629
TI  - Expression of tobacco mosaic virus coat protein by a cauliflower mosaic virus
      promoter in plants transformed by Agrobacterium.
AB  - The 35S transcript promoter of cauliflower mosaic virus directs the synthesis of
      an abundant RNA in infected leaf tissue that is both a template for reverse
      transcription during virus replication and also a polycistronic mRNA. The 35S
      promoter was isolated and linked to a cDNA of the 3' end of tobacco mosaic virus
      that encodes the coat protein of this single-stranded RNA virus. After
      transformation of this gene construction into tobacco plants using a disarmed
      Agrobacterium binary vector, viral coat protein synthesis was detected in
      transformed leaf tissue. A chimaeric 35S coat protein RNA was detected in
      transformed callus.

PMID- 16453630
TI  - Distribution of Ultrabithorax proteins in Drosophila.
AB  - We have used a monoclonal antibody to examine the distribution of Ultrabithorax
      (Ubx) proteins in Drosophila embryos and imaginal discs by immunofluorescence.
      Ubx proteins are nuclear and show a spatially restricted distribution in the
      nervous system, epidermis and mesoderm. Labelling extends from the first thoracic
      segment (T1) to the eighth abdominal segment (A8) in the midline cells, from T2
      to A8 in the ventral nervous system and epidermis and from A1 to A8 in the
      somatic mesoderm. In the nervous systems and epidermis the patterns of labelling
      exhibit a repeat unit, the Ubx metamere, that is out of phase with the segmental
      repeat unit. At least in the epidermis this repeat unit appears to extend between
      anterior-posterior compartment boundaries and consists of a posterior compartment
      together with the succeeding anterior compartment. The most prominently labelled
      metamere in the nervous system and epidermis is that comprising the posterior
      region of T3 and the anterior region of A1. Within each metamere the nuclei are
      heterogeneously labelled. Clear heterogeneity of labelling is also seen amongst
      the nuclei of the T3 imaginal discs.

PMID- 16453631
TI  - Isolation and characterization of the zeste locus of Drosophila.
AB  - The zeste gene of Drosophila regulates the expression of certain other genes like
      white, bithorax and decapentaplegic in a manner dependent on chromosome pairing.
      The genetic evidence suggests that its product interacts with the genes at the
      level of transcription. We have cloned the zeste region from fragments
      microdissected from the 3A1-4 region of the X chromosome and mapped the
      breakpoints of several rearrangements which localise the gene. We have isolated
      dysgenic zeste mutants which contain P element sequences inserted in the same
      region. DNA rearrangements were found in some zeste mutants but were not detected
      in the z, z or z mutants. The changes are localised to a Bam 4.0-kb fragment from
      which originates a 2.4-kb RNA species. This transcript is altered in some zeste
      mutants but is not visibly affected in Z or z mutants. The region bears no
      homology to the white gene or its vicinity but cross-hybridises to many other
      genomic sequences in Drosophila.

PMID- 16453632
TI  - Amino acid and cDNA sequences of lysozyme from Hyalophora cecropia.
AB  - The amino acid and cDNA sequences of lysozyme from the giant silk moth Hyalophora
      cecropia have been determined. This enzyme is one of several immune proteins
      produced by the diapausing pupae after injection of bacteria. Cecropia lysozyme
      is composed of 120 amino acids, has a mol. wt. of 13.8 kd and shows great
      similarity with vertebrate lysozymes of the chicken type. The amino acid residues
      responsible for the catalytic activity and for the binding of substrate are
      essentially conserved. Three allelic variants of the Cecropia enzyme are
      identified. A comparison of the chicken and the Cecropia lysozymes shows that
      there is a 40% identity at both the amino acid and the nucleotide level. Some
      evolutionary aspects of the sequence data are discussed.

PMID- 16453633
TI  - A new member of the polyomavirus family: the hamster papovavirus. Complete
      nucleotide sequence and transformation properties.
AB  - [This corrects the article on p. 1279 in vol. 4, PMID: 2988942.].

PMID- 16453634
TI  - Mutants of Polysphondylium pallidum altered in cell aggregation and in the
      expression of a carbohydrate epitope on cell surface glycoproteins.
AB  - Mutants of the cellular slime mold Polysphondylium pallidum have been selected
      using a cell sorter and a fluorescentlabeled monoclonal antibody, mAb 293. This
      antibody blocks cell adhesion when applied as Fab, and recognizes a carbohydrate
      epitope containing L-fucose. This epitope is expressed on the cell surface and is
      present on >10 membrane glycoproteins of different apparent mol. wts. Twenty
      mutants were obtained which did not bind mAb 293 when tested at 2 h of
      starvation. After longer periods of starvation the epitope became detectable in
      the mutants. In all these mutants aggregation patterns were atypical. Generally
      streams of cells that were radially orientated around aggregation centers were
      missing or were much shorter than in wild-type. Genetic analysis demonstrated
      that aberrant aggregation was linked to the alteration in carbohydrate epitope
      expression. One mutant was unstable and gave rise to subclones in which almost no
      antibody binding was observed, even after 24 h of starvation, and only few
      aggregation centers with no streams or very short ones were formed. These results
      indicate that the capability of the cells to aggregate is correlated with the
      exposure on their surfaces of the carbohydrate epitope recognized by mAb 293,
      whose function in development remains to be established.

PMID- 16453635
TI  - Nucleotide sequences of STE2 and STE3, cell type-specific sterile genes from
      Saccharomyces cerevisiae.
AB  - The nucleotide sequences of STE2 and STE3, cell type-specific sterile genes of
      Saccharomyces cerevisiae, were determined; major open reading frames encode 431
      and 470 amino acids, respectively. STE2 and STE3 proteins seem to be folded in a
      similar fashion and are likely to be membrane-bound. Both consist of seven
      hydrophobic segments in each NH(2)-terminal region with a long hydrophilic domain
      in each COOH-terminal region. However, the two putative gene products do not
      exhibit extensive sequence homology. The STE2 protein has no obvious hydrophobic
      signal peptide; the NH(2) terminus of the STE3 protein might serve as a signal
      peptide. The STE2 transcript, 1.7 kb, was detected in MATa strains but not in
      MATalpha strains, while the STE3 transcript, also 1.7 kb, was detected only in
      MATalpha cells. In STE2, two canonical TATA sequences are located 18 and 27 bp
      upstream of the mRNA start site, which has been mapped 32 bp before the initiator
      ATG codon, while STE3 contains a similar sequence (TATAGA), which is preceded by
      a long AT sequence, 140 bp upstream of the initiator ATG codon. Transcription of
      STE2 in a cells seems to be enhanced by exogenous alpha-factor.

PMID- 16453636
TI  - Reverse gyrase; ATP-dependent type I topoisomerase from Sulfolobus.
AB  - Reverse gyrase, a topoisomerase which introduces positive superhelical turns into
      DNA, has been purified from Sulfolobus to near homogeneity. It is a single
      polypeptide with a mol. wt. of 120 000 as determined by denaturing gel
      electrophoresis. Contrary to a previous report, it is a type I topoisomerase as
      judged by the linking-number change of closed circular DNA topoisomer. Unlike
      other known type I topoisomerases, ATP or dATP is required for introducing
      positive superhelical turns. In order to relax negatively supercoiled DNA, other
      nucleotide triphosphates (XTP) are also effective with low efficiency. In the
      absence of either XTP or divalent cations, the enzyme introduces nicks into
      closed circular DNA when the reaction is stopped by SDS. This suggests that
      reverse gyrase cuts one of the two strands of DNA in the course of its enzymatic
      reaction.

PMID- 16453637
TI  - Light-inducible and tissue-specific expression of a chimaeric gene under control
      of the 5'-flanking sequence of a pea chlorophyll a/b-binding protein gene.
AB  - We have investigated the regulatory functions of the 5'-flanking sequences of a
      chlorophyll a/b-binding protein gene from Pisum sativum, using the neomycin
      phosphotransferase (II) activity from Tn5 as an enzymatic reporter. We show that
      0.4 kb of the upstream flanking sequences of this gene are sufficient for both
      organ-specific and light-regulated expression of our chimaeric constructs in
      transformed tobacco plants. In addition, we show that sequences farther upstream
      have a significant influence on the level of transcription of these
      constructions.

PMID- 16453638
TI  - Construction of a heat-inducible gene for plants. Demonstration of heat-inducible
      activity of the Drosophila hsp70 promoter in plants.
AB  - A chimeric gene containing the neomycin phosphotransferase II coding region under
      the control of the hsp70 promoter from Drosophila was integrated and found to be
      expressed, in a heat-regulated fashion, in tobacco tissue.

PMID- 16453639
TI  - Amino acid sequence of the ;pathogenesis-related' leaf protein p14 from viroid
      infected tomato reveals a new type of structurally unfamiliar proteins.
AB  - We have established the complete sequence of the 130 amino acid residues of the
      pathogenesis-related (PR) protein p14 accumulating in tomato leaves infected with
      the viroid of the spindle tuber disease of potato (PSTV) and partial sequences of
      the PR protein 1a which accumulates in tobacco mosaic virus-infected tobacco
      leaves. Both PR proteins are closely related to each other. However, no homology
      could be found between the sequence of p14 and any of the 3061 published protein
      sequences compiled in the protein sequence database at present. Thus, p14
      represents not only the first completely sequenced PR plant protein but also a
      new type of structurally unfamiliar proteins whose biological function in the
      diseased plant remains to be elucidated.

PMID- 16453640
TI  - Mapping and expression of a regulatory nitrogen fixation gene (fixD) of Rhizobium
      meliloti.
AB  - A 3.5-kb HindIII fragment from the main nif/fix (nitrogen fixation) gene cluster
      of Rhizobium meliloti was characterized by studying its expression in Escherichia
      coli minicells. A coding region for two polypeptides of 68 K and 66 K was mapped
      using Tn5 insertions and hybrid fusion polypeptides. DNA sequence analysis of
      this region revealed the presence of an open reading frame capable of coding for
      a polypeptide of 59.9 K mol. wt. This coding region was designated fixD.
      Plasmids, constitutively expressing this fixD gene from vector promoters,
      activated a nifHD-lacZ fusion in E. coli at a low level. Higher levels of
      activation were obtained following an enhanced expression of the fixD gene in
      plasmid pRmW541 which was achieved by inducing deletions between the vector
      promoter and the fixD gene. Sequencing of these deletion mutants showed that, in
      most cases, fusion polypeptides of the fixD gene product and the aphI
      (aminoglycoside-3'-phosphotransferase) gene product were sufficient for
      activation. In E. coli the activation is strictly dependent upon a functional
      glnF (ntrA) gene.

PMID- 16453641
TI  - Isolation of caudal, a Drosophila homeo box-containing gene with maternal
      expression, whose transcripts form a concentration gradient at the pre-blastoderm
      stage.
AB  - We report the isolation and characterization of caudal (cad), a previously
      unknown Drosophila homeo box-containing gene from the 38E region on the left arm
      of the second chromosome. This homeo box has diverged from the prototype sequence
      in Antennapedia, but contains subregions which are highly homologous. By Northern
      analysis and in situ hybridization experiments two transcripts of 2.4 kb were
      found to accumulate in nurse cells and in the oocyte during oogenesis. These
      transcripts generate a transient concentration gradient along the antero
      posterior axis at the syncytial blastoderm stage. At the cellular blastoderm
      stage transcripts accumulate in a single band from 13-19% egg length at the
      posterior end. One zygotic transcript of 2.6 kb is detected. At later stages this
      transcript is localized in ectodermally and endodermally derived tissues such as
      the proctodeum, the Malpighian tubules and the posterior midgut. The 2.6-kb
      transcript is detectable until the onset of metamorphosis.

PMID- 16453642
TI  - Two genes in Balbiani ring 2 with metabolically different 75S transcripts.
AB  - Balbiani ring 2 (BR2) in salivary glands of Chironomus pallidivittatus and C.
      tentans (two sibling species of the subgenus Camptochironomus) is a favoured
      model system for studies of gene organization and transcript formation. Here we
      show that BR2 is more complex than hitherto believed, containing two 75S RNA
      producing genes, BR2a and BR2b, present in different 35-40 kb blocks of DNA. The
      transcripts hybridizing to two different repeat units originating in BR2 differ
      in size. Further support for the presence of two genes comes from RNA studies
      during experimentally induced BR2 regression. The amounts of BR2a RNA per cell
      remain more or less constant throughout the course of the experiment, whereas the
      BR2b RNA decreases considerably. Under normal conditions there is 5-6 times more
      BR2a RNA than BR2b RNA. This ratio increases 3-fold under experimental
      conditions. BR2a and BR2b, although partially homologous, contain repeat units
      with characteristic differences. BR2a contains a repeat unit that is much more
      similar to a BR1 repeat than it is to the BR2b repeat. The possibility is
      discussed that a Balbiani ring in general represents an integrated set of active
      genes rather than a singe gene.

PMID- 16453643
TI  - Identification and molecular analysis of a multigene family encoding calliphorin,
      the major larval serum protein of Calliphora vicina.
AB  - A library of Calliphora vicina genomic DNA was constructed in the lambdaEMBL3
      vector and screened for recombinant phages containing chromosomal segments
      encoding calliphorin, the major larval serum protein (LSP) of Calliphora. A large
      series of recombinants hybridizing with in vitro labelled poly(A) RNA from
      Calliphora larval fat bodies and with specific probes derived from the LSP-1
      genes of Drosophila melanogaster was isolated. Five of these phages, chosen at
      random, were shown by hybrid selection to retain calliphorin mRNA specifically.
      Eleven calliphorin mRNA-homologous regions were located on restriction maps of
      these phages by hybridization with 5' end-labelled poly(A) RNA from Calliphora
      larval fat bodies. Each phage contains at least two calliphorin genes arranged in
      direct repeat orientation and seperated by 3.5-5 kb intergenic regions. The genes
      display similar but not identical restriction patterns. Filter hybridization and
      heteroduplex analysis indicate that they share a detectable homology with the LSP
      1beta gene of D. melanogaster. Whole genome Southern analysis showed that these
      genes belong to a large family of closely related calliphorin genes which were
      found by in situ hybridization to polytene chromosomes of trichogen cells to be
      clustered in region 4a of chromosome 2 of Calliphora vicina.

PMID- 16453645
TI  - Specific targeting of membrane nodulins to the bacteroid-enclosing compartment in
      soybean nodules.
AB  - Rhizobium bacteroids in nodule cells are surrounded by the peribacteroid membrane
      (pbm), which is derived from the host plasma membrane during infection. The pbm
      was purified from R. japonicum 61A76-induced soybean nodules and analyzed by
      comparing it with the host cell plasma membrane for the presence of nodulins,
      nodule-specific plant proteins. Nodulins were found in pbm by reacting Western
      blots with a nodule-specific antiserum raised against the pbm. Peribacteroid
      fluid (the fluid enclosed in the pbm) was also found to contain several nodulins.
      The pbm nodulins were confirmed to be of plant origin by in vitro translation of
      poly(A) nodule mRNA followed by immunoprecipitation by the nodule-specific
      antiserum. Antibodies raised against a synthetic peptide corresponding to a
      repeated domain in nodulin-24, a pbm nodulin, and the nodule-specific pbm
      antiserum reacted exclusively with the pbm. The absence of pbm-nodulins in the
      plasma membrane suggests that the infected cells direct the intracellular
      transport of the pbm nodulins exclusively to this de novo synthesized subcellular
      compartment essential for symbiotic nitrogen fixation.

PMID- 16453646
TI  - Accumulation and assembly of soybean beta-conglycinin in seeds of transformed
      petunia plants.
AB  - A gene encoding the alpha'-subunit of beta-conglycinin, a seed storage protein of
      soybean (Glycine max), was transformed into petunia cells on a disarmed Ti
      plasmid of Agrobacterium tumefaciens, and plants were regenerated. Transcripts of
      the introduced gene accumulated in immature embryos but not in leaves of the
      transformed plants. Soybean protein was first detected immunologically in
      proteins extracted from embryos at 10 days post pollination (d.p.p.), concurrent
      with the accumulation of subunits of the major petunia seed proteins. Between 10
      and 16 d.p.p. the primary soybean protein detected had an apparent mol. wt. of 55
      kd. The 76-kd alpha'-subunit and several smaller polypeptides accumulated between
      16 and 24 d.p.p., when seeds had matured. Polypeptides <76 kd probably resulted
      from specific proteolytic cleavage of the alpha'-subunit. The alpha'-subunit and
      the smaller polypeptides assembled into multimeric proteins with sedimentation
      coefficients of 7-9S, similar to the sedimentation coefficients of beta
      conglycinins isolated from soybean seeds. This transformation and expression
      system should be ideally suited for testing gene mutations to alter the amino
      acid composition of these seed storage proteins.

PMID- 16453647
TI  - Differential expression of the eight genes of the petunia ribulose bisphosphate
      carboxylase small subunit multi-gene family.
AB  - Of the eight nuclear genes in the plant multi-gene family which encodes the small
      subunit (rbcS) of Petunia (Mitchell) ribulose bisphosphate carboxylase, one rbcS
      gene accounts for 47% of the total rbcS gene expression in petunia leaf tissue.
      Expression of each of five other rbcS genes is detected at levels between 2 and
      23% of the total rbcS expression in leaf tissue, while expression of the
      remaining two rbcS genes is not detected. There is considerable variation (500
      fold) in the levels of total rbcS mRNA in six organs of petunia (leaves, sepals,
      petals, stems, roots and stigmas/anthers). One gene, SSU301, showed the highest
      levels of steady-state mRNA in each of the organs examined. We discuss the
      differences in the steady-state mRNA levels of the individual rbcS genes in
      relation to their gene structure, nucleotide sequence and genomic linkage.

PMID- 16453648
TI  - Photoregulated expression of a pea rbcS gene in leaves of transgenic plants.
AB  - A 2.4-kb pea genomic fragment, containing a member (rbcS-E9) of the multigene
      family encoding the small subunit (rbcS) of ribulose-1,5-bisphosphate
      carboxylase, was inserted into a non-oncogenic, Ti-plasmid vector and introduced
      into the genomes of Petunia hybrida (Mitchell) and Nicotiana tabacum (SR1) plants
      by in vitro transformation. Petunia and tobacco plants containing the introduced
      pea rbcS-E9 gene were regenerated from protoplasts. In these transgenic plants
      the rbcS-E9 gene is transcribed accurately using its own promoter and its
      expression is light-induced and organ-specific. A deletion mutant with 352 bp of
      5'-upstream sequence still retains photoinducibility and leaf-specific
      expression. Clonal analysis of independent transgenic petunia plants revealed
      that chromosomal positions in the recipient plant genome affect the quantitative
      but not qualitative aspects of rbcS-E9 expression.

PMID- 16453649
TI  - Isolation and identification of TL-DNA/plant junctions in Convolvulus arvensis
      transformed by Agrobacterium rhizogenes strain A4.
AB  - We have constructed a Charon 4A phage library containing insert DNA isolated from
      a morning glory (Convolvulus arvensis) plant (clone 7) regenerated from a root
      organ culture incited by Agrobacterium rhizogenes, strain A4. Using a subcloned
      region of the Ri plasmid as P-labeled probe, two lambda clones containing most of
      the 'left' T-DNA (TL) region were isolated. One of these lambda clones contains
      the left TL-DNA/plant junction, which was located by comparing nucleotide
      sequences from the appropriate regions of the Ri plasmid and this lambda clone. A
      25-bp sequence found near this left TL-DNA/plant junction matches the 25-bp
      terminal sequence found at or near T-DNA/plant junctions of both nopaline- and
      octopine-type A. tumefaciens Ti plasmids. A possible location for the right Ri TL
      DNA/plant junction in C. arvensis clone 7 was found by obtaining the nucleotide
      sequence surrounding its mapped location. Hybridization of plant DNA found
      adjacent to the left TL-DNA/plant junction against total C. arvensis DNA shows
      that this T-DNA integration occurred in a plant DNA region that does not contain
      highly repetitive DNA sequences. Nucleotide sequence analysis of 1004 bp of this
      plant DNA revealed no complete or partial open reading frames, but this plant DNA
      does have the potential to form various secondary structures which might play a
      role in the T-DNA integration event.

PMID- 16453650
TI  - The nodD gene of Rhizobium leguminosarum is autoregulatory and in the presence of
      plant exudate induces the nodA,B,C genes.
AB  - To analyse nod gene expression in Rhizobium leguminosarum, a broad host-range
      lacZ protein fusion vector was constructed. Two protein fusions, nodC-lacZ and
      nodD-lacZ, were used to measure the regulation of expression of the promoters of
      the nodA,B,C and the nodD transcripts by measuring the induced levels of beta
      galactosidase activity in R. leguminosarum. In the absence of plant root exudate
      the nodD-lacZ hybrid was expressed but the nodC-lacZ hybrid was not. The
      expression of the nodD-lacZ hybrid was repressed in R. leguminosarum strains
      containing an intact cloned nodD gene indicating that the nodD gene is
      autoregulatory. The induction of the nodC-lacZ hybrid required both the nodD gene
      and a component present in plant root exudate. Therefore the nodD gene acts both
      as a repressor and as an activator of gene expression. The nodD gene is adjacent
      to nodA and transcribed divergently from nodA,B,C with only approximately 300
      nucleotides between the coding regions of nodA and nodD. Within this intergenic
      region is a unique BclI site and, using nodC-lacZ or nodD-lacZ translational
      fusions with this BclI site as an end point, no induction of nodC-lacZ or nodD
      lacZ was observed. Therefore the promoters of nodD and nodA,B,C overlap at least
      at this region, and the regulation of these overlapping promoters appears to be
      controlled by the nodD protein which becomes an activator only in the presence of
      a component from plant exudate.

PMID- 16453651
TI  - A PIF-dependent recombinogenic signal in the mitochondrial DNA of yeast.
AB  - From their recombination properties, tandem rho mutants of the mitochondrial
      genome of Saccharomyces cerevisiae were divided into two categories. In crosses
      between PIF-independent rho and rho strains, the recombination frequency is low
      and similar in PIF/pif and pif/pif diploids. In crosses between PIF-dependent rho
      and rho strains, the recombination frequency is stimulated 10-50 times in PIF/pif
      diploids and is drastically decreased in pif/pif diploids. These results suggest
      that a recombinogenic signal is present in the mitochondrial (mt) DNA of PIF
      dependent rho clones. This signal is not recognized in pif mutants. Sequence
      analysis of a series of small (<300 bp) overlapping tandem rho genomes located in
      the ery region of the 21S rRNA gene led us to identify an essential element of
      this signal within a 41-bp A+T sequence exhibiting over 26 bp a perfect dyad
      symmetry. However the recombinogenic signal is not sequence-specific since the
      sequence described above does not characterize PIF-dependent rho clones located
      in the oli1 region. Our results rather suggest that the recombinogenic signal is
      related to the topology of rho DNA. Denaturated sites in the double helix or
      cruciform structures elicited by local negative supercoiling might be preferred
      sites of the initiation of recombination.

PMID- 16453652
TI  - Transposon-like properties of the major, long repetitive sequence family in the
      genome of Physarum polycephalum.
AB  - A family of long, highly-repetitive sequences, referred to previously as ;HpaII
      repeats', dominates the genome of the eukaryotic slime mould Physarum
      polycephalum. These sequences are found exclusively in scrambled clusters. They
      account for about one-half of the total complement of repetitive DNA in Physarum,
      and represent the major sequence component found in hypermethylated, 20-50 kb
      segments of Physarum genomic DNA that fail to be cleaved using the restriction
      endonuclease HpaII. The structure of this abundant repetitive element was
      investigated by analysing cloned segments derived from the hypermethylated
      genomic DNA compartment. We show that the ;HpaII-repeat' forms part of a larger
      repetitive DNA structure, approximately 8.6 kb in length, with several structural
      features in common with recognised eukaryotic transposable genetic elements.
      Scrambled clusters of the sequence probably arise as a result of transposition
      like events, during which the element preferentially recombines in either
      orientation with target sites located in other copies of the same repeated
      sequence. The target sites for transposition/recombination are not related in
      sequence but in all cases studied they are potentially capable of promoting the
      formation of small ;cruciforms' or ;Z-DNA' structures which might be recognised
      during the recombination process.

PMID- 16453653
TI  - Cloning of the homeotic Sex combs reduced gene in Drosophila and in situ
      localization of its transcripts.
AB  - We have extended our ;chromosomal walk' in the Antennapedia-complex (ANT-C) by
      isolating overlapping DNA sequences spanning the chromosomal segment between
      Antennapedia (Antp) and Deformed (Dfd). The transcription units, homeoboxes and M
      repeats were mapped within this region. Four transcription units Antp, fushi
      tarazu (ftz), Sex combs reduced (Scr) and Dfd contain both a homeobox and an M
      repeat, whereas at least two additional transcription units, x and z, were found
      to lack these elements. The Scr locus was identified by deletion mapping. It
      consists of at least two exonic regions separated by a large intron. The homeobox
      is located in the 3' exon and is 82% homologous to the one in Antp. Scr encodes a
      major 3.9-kb RNA. A corresponding cDNA clone was used as a probe for in situ
      hybridization to sections of various embryonic stages. At gastrula stages Scr
      transcripts accumulate in the posterior head and the anterior thoracic region of
      the germ band. At later stages a strong accumulation of transcripts is observed
      in the suboesophageal and the prothoracic ganglion of the ventral nervous system.

PMID- 16453654
TI  - Expression of the Drosophila white gene under the control of the hsp70 heat shock
      promoter.
AB  - We have used P-mediated transformation to introduce into the Drosophila genome
      transposons containing the hsp-70 heat shock promoter (hsp) placed at different
      distances upstream of the white gene. Using these constructions we found a strong
      terminator 250 nucleotides upstream of the white transcription start. When all
      white upstream sequences are deleted and the hsp is fused to the white leader
      region, white transcription is under hsp control, however, flies carrying this
      construction have red eyes even at low temperature, due to the basal level of
      activity of the hsp. High levels of transcription are obtained after heat shock
      but about half of the transcripts are incompletely spliced. One transformed line
      carries the transposon integrated near the heterochromatin. These flies have very
      pale eyes but develop strongly pigmented, variegated eyes if heat shocked in the
      first 2 days of the pupal stage. Heat shocks after eclosion have no effect on eye
      pigmentation. The properties of these transposons also indicated that the control
      sequences required for Zeste interaction lie > 1 kb upstream of the white
      transcription start while those required for dosage compensation are close to the
      gene.

PMID- 16453655
TI  - Successive transposition explosions in Drosophila melanogaster and reverse
      transpositions of mobile dispersed genetic elements.
AB  - Transposition outbursts occur in the destabilized Drosophila melanogaster strain
      ct carrying a mutation in the locus cut induced by an insertion of mdg4. While
      the distribution of mobile genetic elements remained unchanged in the great
      majority of germ cells, in a few cells numerous transpositions had occurred
      involving mdg (copia-like), fold-back and P-elements. We used in situ
      hybridization to analyze the distribution of five families of mdg elements in the
      X-chromosome during several consequent mutational changes in D. melanogaster.
      Each of them was accompanied by many changes in mdg localization, all of which
      occurred in one and the same cell. Thus, we could observe the series consisting
      of up to five successive transposition explosions leading to an almost complete
      change in the distribution of the mdg elements tested. We also found that in the
      course of successive transposition explosions, mdg elements often inserted into
      those sub-sections of the X-chromosome where they had previously been located.
      This phenomenon, designated as reverse directed transposition, was studied in
      more detail on insertion into the locus yellow. The rate of reverse transposition
      of the same mdg element to the corresponding locus was 10-100 times as high as
      that of primary insertion. In some cases, ;the transposon shuttle' into and out
      of the locus was observed. The existence of ;transposition memory' partially
      explains the specificity of mdg localization in closely related strains as well
      as the co-ordinated behaviour of different mdg elements in independent
      transposition explosions. The evolutionary significance of transposition
      explosions and directed reverse transposition (transposon shuttle) is discussed.

PMID- 16453656
TI  - The nature of unstable insertion mutations and reversions in the locus cut of
      Drosophila melanogaster: molecular mechanism of transposition memory.
AB  - The segment of the locus cut containing the mobile genetic element mdg4 (gypsy)
      insertions which induce unstable ct and ct mutations has been cloned. Both
      mutations depend on the insertion of mdg4 into the same sequence, which coincides
      with that in ct allele. The ct mutation differs from ct by additional insertion
      of a novel mobile element jockey into mdg4. Jockey is 2.8 kb long, represented by
      2-100 copies per genome, very homogeneous and lacks long terminal repeats (LTRs).
      The excision of mdg4 takes place in stable ct reversions. On the other hand, a
      complete single LTR is retained in the case of unstable ct reversions
      characterized by a high level of reverse directed transpositions of mdg4 into the
      locus cut. The LTR serves as a guide for reinsertion of mdg4 itself or mdg4 with
      jockey into the same site of the genome. A possible mechanism of transposition
      memory (homologous recombination with extrachromosomal circular DNA) is
      discussed.

PMID- 16453657
TI  - The regulatory domain of a larval serum protein gene in Drosophila melanogaster.
AB  - DNAse I hypersensitive sites have been shown to be present at the 5' end of each
      of the larval serum protein genes (LSPs) when they are expressed in the fat body.
      They are absent from the same inactive genes in embryos. A 4.4-kb genomic
      fragment containing the coding region for LSP 1 alpha and 1.5 kb of 5'-flanking
      sequence has been reintroduced into the germ line of a strain containing an
      electrophoretic variant form of the alpha gene. The expression of the
      reintegrated gene is normal with respect to the amount of protein produced and
      the temporal and spatial distribution of the transcript. A comparison has been
      made of the chromatin configuration of the reintroduced and endogenous alpha
      genes and the same pattern of DNase I hypersensitivity is found. The
      hypersensitive regions have been located on the 5' sequence of the LSP 1 alpha
      gene and their sequences compared with known hypersensitive regions of other
      genes.

PMID- 16453658
TI  - Developmentally regulated transcription of Dictyostelium discoideum plasmid Ddp1.
AB  - The presence of high copy number plasmid DNA has been described for several
      independent wild isolates of the lower eukaryote Dictyostelium discoideum, a
      model organism in developmental biology. The function of these plasmids has
      remained unclear so far. To understand the possible functions of the plasmids we
      have analyzed the transcription of one plasmid, Ddp1, in the wild strains NC4 and
      V12. The plasmid is transcribed in an identical fashion in both strains. Ddp1
      codes for three RNA species in growth-phase cells, at least two of which are
      present in the poly(A) fraction. RNA isolated from cells of different
      developmental stages revealed the existence of five more transcripts, the
      majority of them being found in the poly(A) fraction. These transcripts are
      present at distinct time points during development. Both growth-phase and
      development-specific transcripts were found exclusively in Ddp1-containing
      strains. Mapping of the transcripts to the plasmid showed that some of them
      originated from the same area. These results indicated an overlapping of their
      coding regions.

PMID- 16453659
TI  - Probing an adhesion mutant of Dictyostelium discoideum with cDNA clones and
      monoclonal antibodies indicates a specific defect in the contact site A
      glycoprotein.
AB  - Expression of developmentally regulated membrane proteins of aggregating cells of
      Dictyostelium discoideum is subject to several control mechanisms. One of them
      involves periodic cyclic-AMP pulses as signals for gene expression. To increase
      the probability of selecting mutants specifically defective in the contact site A
      (csA) glycoprotein, one of the characteristic proteins of aggregating cells, we
      have bypassed the requirement for both cyclic-AMP pulses and another control
      element by two runs of mutagenesis. A ;double bypass' mutant, HG592, was obtained
      which aggregated in nutrient medium where wild-type did not develop. Mutants
      defective in expression of the csA-glycoprotein were selected from HG592 by
      fluorescence-activated cell sorting and colony immunoblotting using a monoclonal
      antibody specific for that protein. One among 51 csA-negative mutants, HG693,
      specifically lacked the capability of forming EDTA-stable intercellular contacts.
      It acquired chemotactic responsiveness and developed into fruiting bodies.
      Expression of the transcripts for eight developmentally regulated proteins was
      determined in HG693. Seven of the RNA species were normally expressed; they were
      recognized by cDNA clones which had been produced from poly(A) RNA isolated from
      membrane-bound polysomes. The single RNA species which was not substantially
      expressed in HG693 was recognized by a cDNA clone that was obtained by screening
      a lambdagt11 library with an antibody specific for the csA-glycoprotein. When
      probing RNA from wild-type cells, this clone hybridized with a single
      developmentally regulated RNA species of 1.9 kb whose expression was strongly
      enhanced by cyclic-AMP pulses. Appearance of this RNA coincided with the
      expression of the csA-glycoprotein.

PMID- 16453660
TI  - Molecular cloning and characterization of the yeast RAD10 gene and
      characterization of RAD10 protein in E. coli.
AB  - [This corrects the article on p. 1575 in vol. 4, PMID: 3896774.].

PMID- 16453662
TI  - The Antennapedia gene is required and expressed in parasegments 4 and 5 of the
      Drosophila embryo.
AB  - Transcripts homologous to the 5' exon of the Antp gene accumulate in parasegments
      4 and 5 of the Drosophila embryo, where analysis of the cuticular phenotype of
      Antennapedia (Antp) embryos shows that there is a genetic requirement for the
      Antp gene. The pattern of Antp expression is different in different germ layers;
      the mesoderm expresses Antp only in parasegment 5; in the developing nervous
      system and the epidermis the pattern of expression is complex and suggests that
      interactions between different selector genes take place during wild-type
      development. Both genetic requirements and gene expression indicate that
      Antennapedia is the main morphological determinant in parasegment 4; in
      parasegment 5 it probably acts in concert with other selector genes.

PMID- 16453661
TI  - Light-induced expression of the chimeric chalcone synthase-NPTII gene in tobacco
      cells.
AB  - A chimeric gene was constructed containing the light-inducible chalcone synthase
      (chs) promoter from Antirrhinum majus, the neomycin phosphotransferase structural
      sequence from Tn5 as a reporter gene (NPTII) and the termination region from chs
      gene 1 from Petroselinum hortense. This gene was introduced into tobacco plants
      with the help of Ti plasmid-derived plant vectors and NPTII expression was
      measured. Analysis of the chs promoter sequence indicated the position of several
      possible regulatory regions. These were deleted to test their influence on the
      expression of the chs-NPTII gene. The different chimeric genes were all shown to
      be active after transfer to tobacco with the exception of one, in which the
      entire 5' upstream sequence from -1200 to -39 was deleted. The transcription of a
      chimeric gene with a 1.2-kbp 5' upstream promoter sequence was shown to be light
      inducible in tobacco plants. The analysis of various deletions of this 5'
      upstream sequence indicates that a number of sequence motifs have a quantitative
      effect on gene expression. One of these sequence motifs (-564 to -661) contains a
      direct repeat of 47 bp and the sequence GTGGTTAG which corresponds to the
      consensus core sequences observed in animal gene enhancer sequences. Deletion of
      a fragment containing this direct repeat resulted in a reduction of NPTII
      expression by a factor of 5.

PMID- 16453663
TI  - Expression of nodule-specific uricase in soybean callus tissue is regulated by
      oxygen.
AB  - In soybean root nodules the enzyme uricase is expressed concomitantly with nodule
      development. The initial expression of this protein does not depend on active
      nitrogen fixation, as demonstrated by analysis of uricase activity in effective
      and ineffective root nodules. However, the maximal level of uricase activity is
      determined by the infecting Rhizobium japonicum strain. Sterile root cultures and
      callus tissue, devoid of the microsymbiont, were incubated at varying oxygen
      concentrations and analyzed for uricase activity. The specific activity of
      uricase was increased by lowering the oxygen concentration, with the highest
      activity obtained around 4-5% oxygen. The increase in uricase activity was due to
      increased uricase synthesis, as demonstrated by in vivo labelling of callus
      culture followed by immunoprecipitation with antibodies raised against highly
      purified nodule uricase.

PMID- 16453664
TI  - Sequence of gene malG in E. coli K12: homologies between integral membrane
      components from binding protein-dependent transport systems.
AB  - [This corrects the article on p. 2287 in vol. 4.].

PMID- 16453665
TI  - Molecular characterization of messenger RNAs for 'pathogenesis related' proteins
      la, lb and lc, induced by TMV infection of tobacco.
AB  - A cDNA library was made to poly(A)-containing RNA from tobacco mosaic virus (TMV)
      infected Samsun NN tobacco plants and clones corresponding to mRNAs for the
      'pathogenesis-related' (PR) proteins la, lb and lc were identified.One clone was
      found to contain a complete copy of PR-lb mRNA. The structural organization of
      this RNA is: a leader sequence of 29 nucleotides, an open reading frame of 504
      nucleotides encoding a 30 amino acid long signal peptide and a 138 amino acid
      long mature protein, and a 3'-non-coding region of 235 nucleotides. Two other
      clones were found to contain partial copies of PR-la and PR-lc mRNAs. The data
      indicate an -90% homology between the amino acid sequences of PR-la, -lb and -lc.
      Using one of the clones as probe it was shown that in the TMV-inoculated lower
      leaves and the non-inoculated upper leaves of a tobacco plant, the PR-1 mRNAs
      become detectable from 2 and 8 days after inoculation,respectively.

PMID- 16453667
TI  - A sixth subunit of ATP synthase, an F(0) component, is encoded in the pea
      chloroplast genome.
AB  - DNA from pea and tobacco chloroplasts hybridizes specifically with probes derived
      from the gene for a membrane component, the a subunit of ATP synthase of the
      cyanobacterium, Synechococcus 6301. DNA sequence of the hybridizing region of the
      pea plastid DNA has revealed that it encodes a protein of 247 amino acids related
      in sequence to the a subunits of ATP synthase of Escherichia coli, Synechococcus
      and mitochondria. This is the sixth component of chloroplast ATP synthase that is
      plastid coded. The gene is located upstream from the genes for three other ATP
      synthase subunits and a transcript of 6 kb contains coding sequences from each of
      these genes. Thus the subunit a gene is part of a co-transcribed cluster of four
      ATP synthase genes arranged in the order a:c(or III):b(or I):alpha. Two other ATP
      synthase genes, those for beta and epsilon subunits, are known to form a separate
      cluster. These gene arrangements are most closely related to those found in the
      cyanobacterium, Synechococcus 6301. Hence, this finding provides strong evidence
      for a common origin for cyanobacteria and plant chloroplasts.

PMID- 16453669
TI  - Transcription of the cdc2 cell cycle control gene of the fission yeast
      Schizosaccharomyces pombe.
AB  - The cdc2 gene plays a central role in the control of the mitotic cell cycle of
      the fission yeast Schizosaccharomyces pombe. It is required in G1 at start for
      commitment to the mitotic cycle and then again in G2 where it determines the
      timing of mitosis. We have identified the cdc2 gene transcript as a 1.6-kb
      polyadenylated mRNA. This transcript is generated after four introns have been
      spliced out; there is no evidence for differential splicing. The level of cdc2
      transcript does not change during a shift between cell proliferation and
      stationary phase or during the mitotic cell cycle. Overproduction of the cdc2
      transcript does not alter the normal cell cycle. We conclude that the cell cycle
      is not controlled by changes in either the cdc2 transcript level or in its
      processing. A gene adjacent to cdc2 called cdc2L has also been identified. This
      encodes three transcripts of 1.0-1.3 kb in length, at least two of which are cell
      cycle regulated. Their levels peak during S-phase and are increased in certain
      cell cycle mutants. This gene may code for a product which is required for the
      mitotic cell cycle.

PMID- 16453668
TI  - The organisation and interviral homologies of genes at the 3' end of tobacco
      rattle virus RNA1.
AB  - The RNA1 of tobacco rattle virus (TRV) has been cloned as cDNA and the nucleotide
      sequence determined of 2 kb from the 3'-terminal region. The sequence contains
      three long open reading frames. One of these starts 5' of the cDNA and probably
      corresponds to the carboxy-terminal sequence of a 170-K protein encoded on RNA1.
      The deduced protein sequence from this reading frame shows homology with the
      putative replicases of tobacco mosaic virus (TMV) and tricornaviruses. The
      location of the second open reading frame, which encodes a 29-K polypeptide, was
      shown by Northern blot analysis to coincide with a 1.6-kb subgenomic RNA. The
      validity of this reading frame was confirmed by showing that the cDNA extending
      over this region could be transcribed and translated in vitro to produce a
      polypeptide of the predicted size which co-migrates in electrophoresis with a
      translation product of authentic viral RNA. The sequence of this 29-K polypeptide
      showed homology with two regions in the 30-K protein of TMV. This homology
      includes positions in the TMV 30-K protein where mutations have been identified
      which affect the transport of virus between cells. The third open reading frame
      encodes a potential 16-K protein and was shown by Northern blot hybridisation to
      be contained within the region of a 0.7-kb subgenomic RNA which is found in
      cellular RNA of infected cells but not virus particles. The many similarities
      between TRV and TMV in viral morphology, gene organisation and sequence suggest
      that these two viral groups may share a common viral ancestor.

PMID- 16453670
TI  - The structure and expression of maize genes encoding the major heat shock
      protein, hsp70.
AB  - We have isolated and sequenced two maize genomic clones that are homologous to
      the Drosophila hsp70 gene. One of the maize hsp70 clones contains the entire
      hsp70 coding region and 81 nucleotides of the 5' nontranslated sequence. The
      predicted amino acid sequence for this maize protein is 68% homologous to the
      hsp70 of Drosophila. The second maize hsp70 clone contains only part of the
      coding sequence and 1.1 kb of the 5' flanking sequence. This 5' flanking sequence
      contains two sequences homologous to the consensus heat-shock-element sequence.
      Both maize genes are thermally inducible and each contains an intron in the same
      position as that of the heat-shock-cognate gene, hsc1, of Drosophila. The
      presence of an intron in the maize genes is a distinguishing feature in that no
      other thermally inducible hsp70 genes described to date contain an intron. We
      have constructed a hybrid hsp70 gene containing the entire hsp70 coding sequence
      with an intron, and 1.1 kb of the 5' flanking sequence. We demonstrate that this
      hybrid gene is thermally inducible in a transgenic petunia plant and that the
      gene is expressed from its own promoter.

PMID- 16453671
TI  - Transcription and expression of zein sequences in yeast under natural plant or
      yeast promoters.
AB  - Maize genomic fragments containing the regulatory and coding regions of a zein
      gene for a low size class 23-kd protein have been inserted in an interspecific
      Escherichia coli-Saccharomyces cerevisiae expression vector in different
      constructions. The presence of the inducible GAL1-10 upstream activation site
      (UAS) allows us to regulate differentially by carbon sources the transcription of
      the zein gene both under the plant promoter and under the yeast CYC-1 promoter.
      We found that the zein promoter region is properly recognized at the correct
      transcription start, while different termination points occur during
      transcription. The yeast UAS was also shown to function as a typical eukaryotic
      enhancer regardless of its distance or orientation with respect to the plant
      promoter. Yeast cells transformed by a plasmid containing a zein sequence fused
      to a short piece of the CYC-1 gene produced a fused polypeptide, of expected mol.
      wt, in variable amount from 0.2 to 5% depending on the growth phase conditions.

PMID- 16453672
TI  - Isolation and characterization of genes encoding two chitinase enzymes from
      Serratia marcescens.
AB  - Analysis of clones isolated from a cosmid DNA library indicates that the Serratia
      marcescens chromosome contains at least two genes, chiA and chiB, which encode
      distinct secreted forms of the enzyme chitinase. These genes have been
      characterized by inspection of chitinase activity and secreted proteins in
      Escherichia coli strains containing subclones of these cosmids. The two chitinase
      genes show no detectable homology to each other. DNA sequence analysis of one of
      the genes predicts an amino acid sequence with an N-terminal signal peptide
      typical of genes encoding secreted bacterial proteins. This gene was mutagenized
      by cloning a neomycin phosphotransferase gene within its coding region, and the
      insertion mutation was recombined into the parental S. marcescens strain. The
      resulting chiA mutant transconjugant showed reduced chitinase production, reduced
      inhibition of fungal spore germination and reduced biological control of a fungal
      plant pathogen.

PMID- 16453673
TI  - The organisation of chromatin loops: characterization of a scaffold attachment
      site.
AB  - Previous experiments have identified a 657-bp restriction fragment in the non
      transcribed region of the Drosophila histone gene cluster that is specifically
      associated with the histone-depleted nuclear scaffold. The remaining fragments of
      the 5-kb histone repeat were shown to be readily released from the scaffold;
      hence it was proposed that the tandemly repeated cluster of histone genes forms a
      series of 5-kb loops restrained by a nuclear substructure at the sites of
      attachment. Here we show that the attachment fragment is tightly associated with
      protease-sensitive material, whereas the solubilized fragments are relatively
      protein-free. Exonuclease III digestion has been used to map the location of
      protein complexes on the attachment fragment. We have defined two regions of
      approximately 200 bp whose borders provide kinetic barriers to exonuclease III
      degradation. They are separated by a nucleaseaccessible region of approximately
      100 bp. The protected regions are sufficient to mediate association of the
      fragment with the histonedepleted nuclei. Sequence analysis reveals an enrichment
      for sequences closely related to the topoisomerase II cleavage consensus in these
      two domains.

PMID- 16453674
TI  - Hormonal and developmental specificities of transcription lie within a 1.5 kb
      region 5' to the ecdysone inducible Drosophila P1 gene.
AB  - P-element-mediated transformation was used to investigate 5' cis-acting
      regulatory sequences flanking the P1 gene of Drosophila melanogaster, which is
      selectively expressed in the fat body of late third instar larvae under the
      positive control of ecdysone. A hybrid gene was constructed by fusing a 1.5 kb
      DNA fragment directly adjacent to and including the first 25 transcribed bases of
      the P1 gene to the Escherichia coli xanthine guanine phosphoribosyltransferase
      (Ecogpt) gene itself linked at its 3' end to the SV40 t antigen splicing and
      polyadenylation sequences. Five transformed lines of D. melanogaster containing
      only one copy of the hybrid gene were established. In each of these lines the gpt
      sequence is transcribed with the same spatial, temporal and hormonal
      specificities as those of the P1 gene. This provides evidence that control
      elements essential for the ecdysone and developmentally regulated expression of
      P1 are located within a 1.5 kb region 5' to this gene.

PMID- 16453676
TI  - Variable DNA splicing sites of a mitochondrial intron: relationship to the
      senescence process in Podospora.
AB  - The unavoidable phenomenon of senescence in Podospora was previously shown to be
      correlated with the presence of a senescence-specific DNA originating from
      amplification of some regions of the mitochondrial chromosome. The most
      frequently amplified region (alpha) corresponds to the first intron of the gene
      coding for subunit one of cytochrome oxidase. Eleven long-lived mitochondrial
      mutants were isolated. Here we report sequencing experiments that show that three
      of them are deleted for most of intron alpha and for a few base pairs belonging
      to the upstream adjacent exon. We also report an analysis of the residual
      mitochondrial DNA associated with amplification of senescence-specific DNA alpha
      which allows us to identify, in senescent cultures, mitochondrial chromosomes
      lacking sequence alpha. These results taken together suggest that excision of
      intron alpha from the mitochondrial DNA occurs systematically during the aging
      process in Podospora. They furthermore provide the first example of inaccurate
      intron excision at the DNA level.

PMID- 16453675
TI  - Molecular characterization of mutant actin genes which induce heat-shock proteins
      in Drosophila flight muscles.
AB  - Heat-shock proteins (hsps) are constitutively induced by the mutant actins in the
      Drosophila indirect flight muscles (IFM). We compared primary structures of the
      mutant actin genes (KM75 and HH5) which induce hsps and of the non-inducing
      alleles (KM129 and KM88). The KM75 actin has lost 20 amino acids at the C
      terminus. The HH5 actin has only one amino acid substitution, from Gly-336 to
      Ser. In KM129, the C-terminal part of actin is replaced by novel amino acids.
      KM88 is a null allele, with an amber mutation early in the coding region of the
      mutated actin gene. Although all of the KM75, HH5 and KM129 actins have defects
      near the C-terminus, only hsp-inducing mutant actins cause enlargement of the IFM
      nuclei as well as a disruption of myofibrils even in the presence of two copies
      of the normal genes. We further consider the underlying mechanisms linking these
      features of the hsp-inducing alleles.

PMID- 16453678
TI  - Recombination in a plant virus: template-switching in cauliflower mosaic virus.
AB  - A hybrid plasmid, containing tandemly arranged pieces of two different but well
      defined cauliflower mosaic virus (CaMV) genomes, was used to study the mechanism
      by which infectious viral DNA can escape from transforming DNA. Systemic viral
      infection followed inoculation of Brassica plants with a strain of Agrobacterium
      tumefaciens containing the hybrid plasmid in its T-DNA. Restriction mapping of
      uncloned viral DNA from these plants, and sequencing of relevant portions of
      cloned viral DNA, showed that the majority of viral progeny were probably
      descendants of DNA produced by transcription/reverse transcription of the viral
      genome, thus providing further evidence for the hypothesis that this process is
      normally involved in viral replication. The reverse transcriptase enzyme, which
      is thought to undergo an intramolecular template switch during viral replication,
      is shown to move very close to the 5' end of the terminal repeat on the 35S RNA
      molecule before switching templates. The remaining minority of viral genomes can
      best be explained as arising from products of recombination between homologous
      regions of CaMV DNA.

PMID- 16453679
TI  - The Rhizobium leguminosarum nodulation gene nodF encodes a polypeptide similar to
      acyl-carrier protein and is regulated by nodD plus a factor in pea root exudate.
AB  - The DNA sequence of approximately 3.5 kb of the nodulation (nod) region of the
      Rhizobium leguminosarum symbiotic plasmid pRL1JI was determined. Three open
      reading frames were identified; genes corresponding to these have been called
      nodD, nodE and nodF.nodD is adjacent to nodA and is transcribed in the opposite
      direction. The nodF and nodE genes are downstream of, and transcribed in the same
      direction as, nodD with 667 nucleotides between nodD and nodF and three
      nucleotides separating nodF and nodE. The induction of the nodFE operon requires
      the nodD gene product and a component present in plant root exudate. Regions of
      DNA sequence preceding nodF are similar to those preceding nodA; these sequences
      may be involved in the regulation of the expression of nodA and nodF. Analysis of
      nodD revealed an amino acid sequence similar to the predicted DNA-binding domain
      of known DNA-binding proteins. A protein comparison of the nodF protein showed it
      to be similar to the acyl-carrier protein from Escherichia coli and barley,
      especially around the pantothenate-binding region and on this basis it is thought
      that this protein may be involved in an acyl transfer reaction.

PMID- 16453680
TI  - Cloning and identification of the gene coding for the 140-kd subunit of
      Drosophila RNA polymerase II.
AB  - Genomic clones of Drosophila melanogaster were isolated from a lambda library by
      cross-hybridization with the yeast gene coding for the 150-kd subunit of RNA
      polymerase II. Clones containing a region of approximately 2.0 kb with strong
      homology to the yeast gene were shown to code for a 3.9-kb poly(A)-RNA. Part of
      the coding region was cloned into an expression vector. A fusion protein was
      obtained which reacted with an antibody directed against RNA polymerase II of
      Drosophila. Peptide mapping of the fusion protein yielded a number of spots
      identical with spots derived from the 140-kd subunit of Drosophila RNA polymerase
      II. Sequence comparison of a segment of the Drosophila and the corresponding
      yeast clone yielded a high degree of homology at the protein level also,
      suggesting that we had isolated the gene coding for the 140-kd subunit of RNA
      polymerase II from Drosophila. In situ hybridization localized the DmRP140 gene
      at 88 A/B on chromosome 3 while the DmRP215 gene has previously been localized at
      10 C on the X chromosome. Analysis of the transcripts (7.0 and 3.9 kb) in female
      and male flies shows dosage compensation for the transcription of the DmRP215
      gene.

PMID- 16453681
TI  - Evidence for light-induced 13-cis, 14-s-cis isomerization in bacteriorhodopsin
      obtained by FTIR difference spectroscopy using isotopically labelled retinals.
AB  - We have obtained by Fourier transformed infra-red (FTIR)-spectroscopy BR-K, BR-L
      and BR-M difference spectra of bacteriorhodopsin regenerated with isotopically
      labelled retinals. Thereby, we are able to assign reliably the C(14)-C(15) and
      C=N stretching vibrations of the various intermediates. The lower C(14)-C(15)
      stretching vibration frequency in L as compared with 13-cis protonated Schiff
      base model compounds indicates a 13-cis, 14-s-cis configuration of the retinal in
      this species. The unusually low C=N stretching vibration in K at 1615 cm
      indicates less stabilization of the positive charge at the Schiff base by the
      protein environment. Based on these results, a mechanism is suggested by which
      the stored light energy is transformed into proton transfers.

PMID- 16453684
TI  - Transcription of the tandem array of ribosomal DNA in Drosophila melanogaster
      does not terminate at any fixed point.
AB  - Transcription termination of the polymerase I transcribed rRNA genes is thought
      to occur at or closely behind the end of the 28S gene coding region. We show here
      that this is not the case for Drosophila melanogaster. Nuclease S1 mapping of
      total RNA and a nuclear ;run-on' assay reveal that there is no defined point of
      termination throughout the whole spacer separating the two genes. Since the rRNA
      genes in D. melanogaster are organized in tandem arrays, this implies that
      readthrough transcription of one unit can occur up to, and possibly through, the
      promoter of the next unit. Readthrough transcription might be a component of
      transcription enhancement in a tandem array of genes.

PMID- 16453685
TI  - Dramatic events in ciliate evolution: alteration of UAA and UAG termination
      codons to glutamine codons due to anticodon mutations in two Tetrahymena tRNAs.
AB  - The three major glutamine tRNAs of Tetrahymena thermophila were isolated and
      their nucleotide sequences determined by post-labeling techniques. Two of these
      tRNAs show unusual codon recognition: a previously isolated tRNA(UmUA) and a
      second species with CUA in the anticodon (tRNA(CUA)). These two tRNAs recognize
      two of the three termination codons on natural mRNAs in a reticulocyte system.
      tRNA(UmUA) reads the UAA codon of alpha-globin mRNA and the UAG codon of tobacco
      mosaic virus (TMV) RNA, whereas tRNA(CUA) recognizes only UAG. This indicates
      that Tetrahymena uses UAA and UAG as glutamine codons and that UGA may be the
      only functional termination codon. A notable feature of these two tRNAs is their
      unusually strong readthrough efficiency, e.g. purified tRNA(CUA) achieves
      complete readthrough over the UAG stop codon of TMV RNA. The third major tRNA of
      Tetrahymena has a UmUG anticodon and presumably reads the two normal glutamine
      codons CAA and CAG. The sequence homology between tRNA(UmUG) and tRNA(UmUA) is
      81%, whereas that between tRNA(CUA) and tRNA(UmUA) is 95%, indicating that the
      two unusual tRNAs evolved from the normal tRNA early in ciliate evolution.
      Possible events leading to an altered genetic code in ciliates are discussed.

PMID- 16453686
TI  - The cleavable pre-sequence of an imported chloroplast protein directs attached
      polypeptides into yeast mitochondria.
AB  - The cleavable pre-sequences of imported chloroplast and mitochondrial proteins
      have several features in common. This structural similarity prompted us to test
      whether a chloroplast pre-sequence (;transit peptide') can also be decoded by the
      mitochondrial import machinery. In the green alga, Chlamydomonas reinhardtii, the
      small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (a
      chloroplast protein) is nuclear-encoded and synthesized in the cytosol with a
      transient pre-sequence of 45 residues. The 31 amino-terminal residues of this
      chloroplast pre-sequence were fused to mouse dihydrofolate reductase (a cytosolic
      protein) and to yeast cytochrome oxidase subunit IV (an imported mitochondrial
      protein) from which the authentic pre-sequence had been removed. The chloroplast
      pre-sequence transported both attached proteins into the yeast mitochondrial
      matrix or inner membrane, although it functioned less efficiently than an
      authentic mitochondrial pre-sequence. We conclude that mitochondrial and
      chloroplast pre-sequences perform their function by a similar mechanism.

PMID- 16453687
TI  - Primary structure and differential expression of glutamine synthetase genes in
      nodules, roots and leaves of Phaseolus vulgaris.
AB  - In plants, glutamine synthetase (GS) is the enzyme primarily responsible for the
      assimilation of ammonia into organic nitrogen. In Phaseolus vulgaris a number of
      isoenzymic forms of GS are found, each of which consists of eight subunits of
      mol. wt 41 000-45 000. The GS subunits of P. vulgaris have previously been shown
      to be encoded by a small multigene family and a partial cDNA clone for a nodule
      specific GS subunit has been obtained. We report here the isolation and
      nucleotide sequencing of two essentially full-length GS cDNA clones (pR-1 and pR
      2) from a root cDNA library and the deduced amino acid sequences of the
      corresponding GS subunits (355 amino acid residues each). The coding sequences of
      pR-1 and pR-2 are closely related (80% nucleotide homology, 88% amino acid
      homology), but their 5'- and 3'-untranslated regions have diverged almost
      completely. Both pR-1 and pR-2 are related to, but distinct from, the nodule GS
      clone, pcPvNGS-01 (or pN-1). Hybridization to genomic Southern blots showed that
      the three GS mRNAs are encoded by three seperate genes and indicated the
      existence of a fourth class of GS gene. An S1 nuclease protection assay
      demonstrated the presence of R-1 and R-2 mRNA in both roots and leaves and
      confirmed that expression of the N-1 gene is nodule-specific. Expression of the R
      1 and R-2 genes in the roots did not change significantly during nodulation.
      However, only the R-1 gene is expressed in the nodules themselves, indicating
      that the R-2 gene is specifically repressed during nodule development.

PMID- 16453688
TI  - High yield and stable transformation of the unicellular green alga Acetabularia
      by microinjection of SV40 DNA and pSV2neo.
AB  - SV40 DNA and pSV2neo were microinjected into isolated nuclei of Acetabularia
      mediterranea. The injected nuclei were implanted into anucleate cell fragments of
      the same species. Such combinations not only survived but also formed progeny.
      The F(1), F(2) and F(3) generations of these combinations were analyzed. In the
      case of SV40-treated cells T-antigen was expressed and accumulated in the nuclei
      of all three generations studied as shown by indirect immunofluorescence. Nuclear
      exchange experiments revealed expression of the T-antigen only if a transformed
      nucleus but not if only a transformed cytoplasm was involved. Transformation by
      pSV2neo, a chimeric gene with a selectable marker was demonstrated by the
      induction of G-418 resistance as well as immunofluorescence. Genomic DNA was
      isolated from gametes, originating in cysts from the F(1), F(2) and F(3)
      generations of injected cells, and subjected to Southern analysis. These
      experiments demonstrated that both types of DNA are integrated into the host
      genome.

PMID- 16453689
TI  - Complete sequence and transcript regulation of a cell adhesion protein from
      aggregating Dictyostelium cells.
AB  - Three cDNA clones coding for the contact site A (csA) protein, a cell adhesion
      molecule of Dictyostelium discoideum, were isolated by screening a cDNA library
      with monoclonal antibodies. Two of these clones contained the complete coding
      region for the csA protein of 1542 bp including a sequence of 57 bp coding for
      the leader. The N terminus of the mature protein, as it was published previously,
      was identified in the amino acid sequence derived from both full-length cDNA
      clones. Southern blot analysis suggests the presence of only one csA gene in the
      haploid genome. Accumulation of the csA-specific message of 1.9 kb begins during
      development on nitrocellulose filters at 9 h of starvation, and reaches a maximum
      at 12 h, the time of cell aggregation. Expression of the csA glycoprotein follows
      closely accumulation of the transcripts. In the multicellular slug stage
      following cell aggregation, the amount of csA transcripts rapidly declines to low
      levels.

PMID- 16453690
TI  - Primary structure of a developmentally regulated nicotinic acetylcholine receptor
      protein from Drosophila.
AB  - Acetylcholine is a major excitatory neurotransmitter in the central nervous
      system of insects. Using DNA probes of the Torpedo nicotinic acetylcholine
      receptor (AChR) we have isolated two overlapping cDNA clones encoding a putative
      neuronal AChR protein from the fruitfly, Drosophila melanogaster. The predicted
      mature protein consists of 497 amino acids, has a calculated mol. wt of 57 340
      and shows extensive homology to known AChR subunits from different species along
      its entire amino acid sequence. Northern analysis revealed a hybridizing mRNA of
      3.2 kb in late embryo and in pupae. Expression of the corresponding AChR gene
      thus characterizes periods of neuronal differentiation in Drosophila.

PMID- 16453691
TI  - Activation of the Drosophila hsp27 promoter by heat shock and by ecdysone
      involves independent and remote regulatory sequences.
AB  - Transcription of the Drosophila hsp27 gene is induced both by heat shock and by
      the steroid hormone ecdysone. Deletion analysis of the promoter using a transient
      expression assay in Drosophila tissue culture cells reveals two separate and
      functionally independent regulatory regions, whose positions coincide with
      previously reported DNase I-hypersensitive sites in embryonic chromatin. Ecdysone
      induction is mediated by multiple elements between -579 and -455. Several matches
      to the consensus heat shock regulatory element (HSE) lie between -370 and -270,
      and deletion of these abolishes the response to heat shock. Heat inducibility can
      be restored by the addition of HSE sequences from the hsp70 promoter, even when
      these are placed at the 3' end of the gene. Furthermore, HSEs seperated by >2 kb
      can interact in a cooperative way to promote transcription. Deletion of sequences
      adjacent to the TATA box (-40 to -154) has little effect on induction by either
      heat shock or ecdysone. In this respect, activation of the hsp27 TATA box in
      Drosophila cells differs from the long-range activation of promoters by HSEs or
      viral enhancers in HeLa cells.

PMID- 16453692
TI  - Correlative changes in homoeotic and segmentation gene expression in Kruppel
      mutant embryos of Drosophila.
AB  - Mutations of the segmentation gene Kruppel (Kr) cause deletions of contiguous
      sets of body segments from the middle region of the Drosophila embryo. We have
      monitored expression in situ of three other genes implicated in the establishment
      of the body plan, namely hairy (h), fushi tarazu (ftz) and engrailed (en), in
      mutant Kr embryos. Our results show that the pattern of expression of all three
      genes depends upon Kr activity and are consistent with a hierarchical model of
      segmentation gene activity. In addition, we find that the initial expression of
      the homoeotic selector gene Ultrabithorax(Ubx) follows a novel pattern in Kr
      embroys indicating a close integration of the spatial control of homoeotic and
      segmantation gene expression.

PMID- 16453694
TI  - Lack of the D2 protein in a Chlamydomonas reinhardtii psbD mutant affects
      photosystem II stability and D1 expression.
AB  - D1 and D2, two chloroplast proteins with apparent mol. wt of 32 000-34 000, play
      an important role in the photosynthetic reactions mediated by the membrane-bound
      protein complex of photosystem II (PSII). We have isolated and characterized an
      uniparental, non-photosynthetic mutant of Chlamydomonas reinhardtii and show that
      the mutation is in the chloroplast gene psbD, coding for D2. A 46 bp direct DNA
      duplication in the coding region of the mutant gene causes a frame-shift which
      results in a psbD transcript coding for 186 amino acid residues instead of the
      normal 352. The truncated D2 peptide is never seen, even after pulse-labeling,
      suggesting that the mutant protein is very unstable. In addition, little or no D1
      protein is detected in this mutant although the gene and normal levels of mRNA
      for D1 are present in mutant cells. All other core PSII proteins are synthesized
      and inserted into the membrane fraction, but never accumulate. These results
      suggest that D2 contributes not only to the stabilization of the PSII complex in
      the membrane, but also may play a specific role in the regulation of the D1
      protein, either at the translational or post-translational level.

PMID- 16453695
TI  - Identification of plant promoters in situ by T-DNA-mediated transcriptional
      fusions to the npt-II gene.
AB  - We have constructed an Agrobacterium-mediated plant vector,pHTT88,which upon
      integration into the plant chromosomes can produce transcriptional fusions
      between upstream control elements in the plant genome and the gene for neomycin
      phosphotransferase II (npt-II). The vector is based on a juxtaposition of a T-DNA
      right border to the coding sequence of npt-II. Using this system it is possible
      to isolate kanamycin-resistant plant calli where the site of integration is
      suitably positioned downstream of plant transcription signals. We have
      demonstrated that the NPT-II activity of such tobacco transformants shows
      different tissue-specific patterns of regulation in the regenerated plants. Among
      eight transformants analyzed, we have isolated one gene fusion expressed only in
      roots and others expressed only in stem. The results demonstrate that a gene
      fusion vector can be used effectively in plants to identify and characterize
      regulatory elements.

PMID- 16453696
TI  - The nucleotide sequence of an infectious clone of the geminivirus beet curly top
      virus.
AB  - A number of infectious clones of a Californian isolate of the leafhopper
      transmitted geminivirus beet curly top virus (BCTV) have been constructed from
      virus-specific double-stranded DNA isolated from infected Beta vulgaris and used
      to demonstrate a single component genome. The nucleotide sequence of one
      infectious clone has been determined (2993 nucleotides). Comparison with other
      geminiviruses has shown that the organisation of the genome closely resembles DNA
      1 of the whitefly-transmitted members. The four conserved coding regions of DNA 1
      have highly homologous counterparts in BCTV with the exception of the putative
      coat protein which is more closely related to those of the leafhopper-transmitted
      geminiviruses suggesting a strong interrelationship between coat protein and
      insect vector. A BCTV component equivalent to DNA 2 is not required for virus
      infection or transmission and has not been isolated from infected plants.

PMID- 16453697
TI  - The head activator is released from regenerating Hydra bound to a carrier
      molecule.
AB  - Hydra forced to regenerate a head releases head activator and head inhibitor
      during the first hours after cutting to induce head-specific growth and
      differentiation processes. Analysis of the size distribution demonstrated that
      the head-activator peptide is co-released with (a) large molecular weight carrier
      molecule(s) to which it is non-covalently bound. The carrier-bound head activator
      is fully active on Hydra indicating that a carrier does not hinder the
      interaction with receptors. In contrast to this the head inhibitor is released in
      its naked, low molecular mass form. The association or non-association with a
      carrier molecule results in marked differences in biological properties. The head
      activator has a short range of action, but a long half-life, the head inhibitor
      has a global range of action, but a short half-life. These results provide a
      plausible explanation why two antagonistically acting substances, although they
      are released from the same site and simultaneously nevertheless can give rise to
      a well-defined temporal and spatial pattern of differentiation as occurs, for
      example, during head regeneration in Hydra.

PMID- 16453698
TI  - Mating pheromone-like diffusible factor released by Schizosaccharomyces pombe.
AB  - We demonstrate that a diffusible factor is secreted by h cells of the fission
      yeast Schizosaccharomyces pombe, whose mating pheromones have not been described.
      This factor, tentatively named the h-factor, affects hS. pombe cells and induces
      their elongation under nitrogen-depleted conditions. Circumstantial evidence
      suggests its physiological significance in the mating process. Despite their
      sterility, hras1 cells secrete this factor. However, hras1 cells have apparently
      lost the ability to respond to it. This may suggest that the gene product of S.
      pombe ras1, a homologue of mammalian ras oncogenes, is involved in the mechanism
      for responding to mating pheromones.

PMID- 16453699
TI  - The complete nucleotide sequence of the tobacco chloroplast genome: its gene
      organization and expression.
AB  - The complete nucleotide sequence (155 844 bp) of tobacco (Nicotiana tabacum var.
      Bright Yellow 4) chloroplast DNA has been determined. It contains two copies of
      an identical 25 339 bp inverted repeat, which are separated by a 86 684 bp and a
      18 482 bp single-copy region. The genes for 4 different rRNAs, 30 different
      tRNAs, 39 different proteins and 11 other predicted protein coding genes have
      been located. Among them, 15 genes contain introns. Blot hybridization revealed
      that all rRNA and tRNA genes and 27 protein genes so far analysed are transcribed
      in the chloroplast and that primary transcripts of the split genes hitherto
      examined are spliced. Five sequences coding for proteins homologous to components
      of the respiratory-chain NADH dehydrogenase from human mitochondria have been
      found. The 30 tRNAs predicted from their genes are sufficient to read all codons
      if the ;two out of three' and ;U:N wobble' mechanisms operate in the chloroplast.
      Two sequences which autonomously replicate in yeast have also been mapped. The
      sequence and expression analyses indicate both prokaryotic and eukaryotic
      features of the chloroplast genes.

PMID- 16453700
TI  - Replication of in vitro constructed viroid mutants: location of the pathogenicity
      modulating domain of citrus exocortis viroid.
AB  - Sequence variants from field isolates of citrus exocortis viroid (CEV) that cause
      either mild or severe symptoms on tomato plants have previously been classified
      into two groups, A and B. These groups differ primarily in two domains, P(L) and
      P(R), of the proposed native structure. Infectivity studies with full-length cDNA
      clones of variants from each class have now directly confirmed the original
      correlation between Class A sequences and the severe phenotype and between Class
      B sequences and the mild phenotype. Direct evidence for this correlation could
      only be obtained by using individual sequence variants since field isolates of
      CEV have been shown to contain a mixture of RNA species. The construction and
      infectivity of chimaeric cDNA clones derived from mild and severe sequence
      variants of CEV has demonstrated that novel, infectious viroid molecules can be
      generated in vitro, and that P(L) is the pathogenicity-modulating domain. The
      role of the P(R) domain is not known but infectivity experiments with one
      chimaeric cDNA clone suggest that it may influence the efficiency of the
      infection or replication process of the viroid in the plant.

PMID- 16453701
TI  - cDNA cloning of six mRNAs induced by TMV infection of tobacco  and a
      characterization of their translation products.
AB  - A cDNA library was constructed to 10-15 S poly(A) RNA from tobacco mosaic virus
      (MV)-infected Samsun NN tobacco.By differential colony hybridization of 1400
      transformants,32 clones were obtained corresponding to TMV-inducible tobacco
      mRNAs. These clones were subdivided into six clusters on the basis of cross
      hybridization of the inserts. By Northern blot hybridization it was shown that
      three of the corresponding mRNAs were strongly induced by spraying tobacco plants
      with salicylic acid, whereas one mRNA was weakly induced by this treatment. All
      mRNAs were systemically induced in plants in which only the lower leaves were
      locally infected by TMV. Hybrid-selected translation was performed, using six
      clones representing one cluster each, followed by immunoprecipitation using an
      antiserum to purified pathogenesis-related (PR) proteins. Four clones yielded
      precipitable translation products. One of these clones represented a cluster of
      PR-1 clones, another clone encoded the thaumatin-like (TL) protein of tobacco
      which may correspond to PR-P or -Q.

PMID- 16453702
TI  - Expression dynamics of the pea rbcS multigene family and organ distribution of
      the transcripts.
AB  - We have determined the nucleotide sequence of two members (rbcS-3A and -3C) of
      the pea nuclear gene family encoding the small subunit (rbcS) of ribulose-1,5
      bisphosphate carboxylase. Both rbcS-3A and -3C are interrupted by two introns
      located at the same positions as those of the other three pea rbcS genes.
      Compared with the other pea rbcS genes the rbcS-3C gene has the most divergent 5'
      and 3'-flanking sequences while the rbcS-3A gene has a larger and highly
      divergent intron 1. All five pea rbcS genes are conserved in their coding regions
      but show considerable sequence differences in their 3'-untranslated portion. The
      3' sequence divergence of the rbcS genes has allowed us to use S1 nuclease
      mapping procedures to compare their expression levels in different organs and
      during light induction. All the rbcS genes are differentially expressed in
      various organs of the pea plants; moreover, specific rbcS transcripts are under
      represented in seeds and petals. In leaves there is a 10-fold difference between
      the highest and lowest specific rbcS transcript levels. By quantitating the
      distribution of rbcS transcripts during light, phytochrome and blue light
      induction of immature (etiolated), and mature (green), pea leaves, we show that
      the genes are differentially activated during leaf development.

PMID- 16453703
TI  - Localization of Agrobacterium rhizogenes T-DNA in plant chromosomes by in situ
      hybridization.
AB  - We have used in situ hybridization to determine the sites of insertion of
      Agrobacterium rhizogenes Ri T-DNA in the chromosomes of Crepis capillaris (2n =
      6) transformed roots. Four transformed root lines were obtained by infecting
      Crepis stem segments with A. rhizogenes. Southern hybridization analysis
      indicated that each root line was the result of one or more independent T-DNA
      insertion events. In two root lines, one copy of T-DNA was present; the other two
      root lines each contained two copies of T-DNA. To localize these T-DNA inserts on
      Crepis chromosomes, metaphase spreads were perpared from each root line, and
      hybridized in situ to a biotinlabeled T-DNA probe. The results indicated that T
      DNA was present in a different chromosomal location in each root line, and that
      each chromosome had been a target for T-DNA insertion at least once. In the root
      lines containing two T-DNA inserts, two patterns of integration were observed: in
      one case the T-DNAs were present on separate chromosomes; in the other case the
      two T-DNAs were close together (but not tandemly arranged) on a single
      chromosome. A comparison of these results and those obtained previously for a
      fifth Crepis-transformed root line demostrated that Ri T-DNA does not insert
      preferentially into a particlar chromosomal location.

PMID- 16453704
TI  - Homeotic gene function in the muscles of Drosophila larvae.
AB  - The segmental musculature of Drosophila melanogaster larvae consists of 24-30
      muscles per segment. Unique patterns of muscles are found in the three thoracic
      segments and the first and last abdominal segments; the remaining abdominal
      segments share the same pattern. Mutations in Ultrabithorax (Ubx) cause partial
      transformation of the muscle pattern of larval abdominal segments towards
      metathorax. The muscles of the thorax are not affected. In the first two
      abdominal segments the changes include the loss of at least 11 ;abdominal'
      muscles and the gain of 11 ;thoracic' muscles. Less extensive transformations are
      seen in more posterior abdominal segments. Anterobithorax, bithorax, postbithorax
      and bithoraxoid mutations also induce transformations of the larval musculature.
      Each allelic group affects a domain that is a subset of the entire Ubx domain but
      these domains are not restricted to compartments or segments and may extend
      through as many as five segments. In the muscles the segmental distribution of
      Ubx antigen correlates with the segments affected by Ubx mutations. The different
      domains of Ubx in mesoderm and ectoderm argue that the segmental diversity of the
      muscle pattern is not simply induced by the overlying epidermis and that Ubx
      function in the mesoderm is required for the correct development of abdominal
      segments.

PMID- 16453705
TI  - The suffix sequence is involved in processing the 3' ends of different mRNAs in
      Drosophila melanogaster.
AB  - We describe here the nucleotide sequences of several genomic and mRNA copies of
      the suffix, a short dispersed actively transcribed repeat located at the 3' ends
      of many different genes of Drosophila melanogaster. Only one strand of the suffix
      is transcribed. The patterns of suffix-containing mRNAs vary during development.
      The five randomly selected genomic copies of the suffix are 265 bp long and quite
      conservative in their sequence. The non-transcribed strand is terminated with
      oligo(A) preceded by AATAAA sequence. No repetitive flanking sequences can be
      detected. The three other genomic copies selected by hybridization with suffix
      containing cDNA clones are less conservative, especially in the 5' part. In
      particular, they contain short insertions carrying a polyadenylation signal
      AATAAA at exactly the same position of the suffix. Comparison of genomic and cDNA
      clones shows that mRNAs are polyadenylated at the last nucleotide of these
      insertions. The cDNA clones include the same part of the suffix, from the 39th to
      112th nucleotide. Thus, a segment of the suffix forms the last exon for both
      genes. In one case, the beginning of the last intron coincides with the beginning
      of suffix, creating a very unusual donor splicing site. We conclude that the
      suffix sequence is directly involved in the formation of the last splicing site
      and 3'-end maturation of mRNA, at least in the case of the two genes analysed.

PMID- 16453706
TI  - Functional analysis of the transcriptional control regions of the copia
      transposable element.
AB  - The introduction of copia-based vectors in Drosophila hydei cells results in
      their high-level transient expression and the subsequent establishment of stably
      transformed cell lines containing multiple copies of vector integrated into host
      genomic DNA. Using transformation frequency and transient expression analysis as
      assays of promoter strength, we have defined the regions of copia essential for
      expression. We find that the essential sequences reside within the long terminal
      repeat, but 3' to the site of initiation of copia RNA. Deletion of the consensus
      enhancer-like sequences from copia appears to have no effect on vector
      expression.

PMID- 16453708
TI  - Higher order structure in ribosomal RNA.
AB  - [This corrects the article on p. 1111 in vol. 5, PMID: 3720727.].

PMID- 16453707
TI  - Molecular cloning and transcriptional analysis of the start gene CDC25 of
      Saccharomyces cerevisiae.
AB  - To isolate the CDC25 gene of Saccharomyces cerevisiae we have transformed a cdc25
      1, trp1 strain with a yeast gene bank constructed in YRp7 vector, selecting trp
      clones able to grow at restrictive temperature. From several independent positive
      clones we have recovered a plasmid, called pDGEm-1, that bears a 5-kb genomic
      fragment and is able to give a full complementation of the cdc25-1 mutation. The
      genomic sequence has been subcloned and a good complementation obtained with a 2
      kb fragment. Several stable integrative trp, cdc transformants have been
      constructed. Their genetic and molecular analysis indicates that we have cloned
      the true CDC25 gene. Northern blot hybridization has revealed the presence of a 5
      kb mRNA transcribed by the CDC25 gene. This mRNA is also present in nitrogen
      starved cells and during the re-enter in cell cycle from starvation, suggesting a
      constitutive transcription. Transformants bearing the cloned sequence on
      multicopy plasmid and integrative transformants that bear the CDC25 gene, flanked
      by plasmid sequences, show an altered control of the cell cycle and fail to
      arrest in G1 unbudded phase in stationary phase conditions.

PMID- 16453710
TI  - Monocot and dicot pre-mRNAs are processed with different efficiencies in
      transgenic tobacco.
AB  - A gene encoding the small subunit of ribulose 1,5-bisphosphate carboxylase (rbcS)
      in wheat, a monocot plant, was transferred to tobacco, a dicot plant. The wheat
      gene is not expressed in transgenic tobacco under the control of its own
      promoter, but when transcription is driven by a viral promoter, several wheat
      transcripts accumulate. These include both spliced and unspliced transcripts,
      which are polyadenylated at multiple novel sites in the wheat 3' flanking region.
      Another monocot intron, from the maize Adh-1 gene, is also spliced inefficiently
      in tobacco. These findings contrast results demonstrating efficient processing of
      different rbcS transcripts from pea, a dicot, in transgenic tobacco. This pattern
      may reflect general differences in sequences required for RNA processing in
      monocot and dicot plants.

PMID- 16453711
TI  - The gene III product (P15) of cauliflower mosaic virus is a DNA-binding protein
      while an immunologically related P11 polypeptide is associated with virions.
AB  - Using electron microscopic immunocytochemical staining we demonstrate that the
      product of gene III of cauliflower mosaic virus (CaMV) is associated with viral
      particles. Furthermore, a fusion protein, expressed in bacteria, consisting of
      the N-terminus of beta-galactosidase and the complete gene III protein of CaMV
      showed DNA-binding activity. From these two results, we discuss the possible
      function of this viral polypeptide.

PMID- 16453712
TI  - Assembly of cyanobacterial and higher plant ribulose bisphosphate carboxylase
      subunits into functional homologous and heterologous enzyme molecules in
      Escherichia coli.
AB  - The genes for the large (rbcL) and small (rbcS) subunits of ribulose-1,5
      bisphosphate carboxylase-oxygenase (RuBPCase) from the cyanobacterium
      Synechococcus PCC 6301, and the rbcS gene of wheat, have been expressed in
      Escherichia coli in order to study homologous and heterologous enzyme assembly.
      Synechococcus L subunits expressed in E. coli in the absence of S subunits
      assemble into oligomeric structures without detectable enzyme activity. Co
      expression of L and S subunits, achieved after infection with an M13 recombinant
      phage containing the rbcS gene, restores enzyme activity, thus demonstrating the
      essential role of S in the formation of an active RuBPCase. The S subunit,
      however, is neither required for the solubility nor for the assembly of the L
      subunits into oligomeric forms. The specific activity of the homologous
      Synechococcus RuBPCase can be modulated by changing the intracellular pool size
      of S by phage infection. Heterologous assembly between L subunits of
      Synechococcus and S subunits of wheat can be demonstrated and results in a
      functional enzyme. The hybrid RuBPCase has approximately 10% of the activity of
      the homologous Synechococcus enzyme.

PMID- 16453713
TI  - Pigment-protein interactions in the photosynthetic reaction centre from
      Rhodopseudomonas viridis.
AB  - An X-ray structure analysis of the photosynthetic reaction centre from the purple
      bacterium Rhodopseudomonas viridis provides structural details of the pigment
      binding sites. The photosynthetic pigments are found in rather hydrophobic
      environments provided by the subunits L and M. In addition to apolar
      interactions, the bacteriochlorophylls of the primary electron donor (;special
      pair') and the bacteriopheophytins, but not the accessory bacteriochlorophylls,
      form hydrogen bonds with amino acid side chains of these protein subunits. The
      two branches of pigments which originate at the primary electron donor, and which
      mark possible electron pathways across the photosynthetic membrane, are in
      different environments and show different hydrogen bonding with the protein: this
      may help to understand why only one branch of pigments is active in the light
      driven electron transfer. The primary electron acceptor, a menaquinone (Q(A)), is
      in a pocket formed by the M subunit and interacts with it by hydrophobic contacts
      and hydrogen bonds. Competitive inhibitors of the secondary quinone Q(B) (o
      phenanthroline, the herbicide terbutryn) are bound into a pocket provided by the
      L subunit. Apart from numerous van der Waals interactions they also form hydrogen
      bonds to the protein.

PMID- 16453714
TI  - Integrative transformation of Caenorhabditis elegans.
AB  - A technique for introducing exogenous DNA into the chromosomes of the nematode
      Caenorhabditis elegans is presented. A cloned C. elegans amber suppressor tRNA
      gene, sup-7, is used as a selectable marker. The activity of this amber
      suppressor is selected for by injecting worms which carry an amber termination
      mutation in a gene (tra-3) whose function is required for fertility. Transient
      expression of sup-7 is evidenced by the presence of fertile (rescued) animals in
      the generation after injection. In a fraction of cases, these fertile animals
      give rise to stable suppressor lines (eight have been characterized so far). Each
      of the stable suppressor lines carries injected DNA sequences. The suppressor
      activities have been mapped to chromosomal loci, indicating that the exogenous
      DNA has integrated into the genome. This technique has been used to introduce a
      chimeric gene containing a Drosophila heat shock promoter element fused to coding
      sequences from the Escherichia coli beta-galactosidase gene. This chimeric gene
      functions and is heat inducible in the resulting stably transformed lines.

PMID- 16453715
TI  - An intron in a ribosomal protein gene from Tetrahymena.
AB  - We have cloned and sequenced a single copy gene encoding a ribosomal protein from
      the ciliate Tetrahymena thermophila. The gene product was identified as ribosomal
      protein S25 by comparison of the migration in two-dimensional polyacrylamide gels
      of the protein synthesized by translation in vitro of hybrid-selected mRNA and
      authentic ribosomal proteins. The proteins show strong homology to ribosomal
      protein S12 from Escherichia coli. The coding region of the gene is interrupted
      by a 979-bp intron 68 bp downstream of the translation start. This is the first
      intron in a protein encoding gene of a ciliate to be described at the nucleotide
      sequence level. The intron obeys the GT/AG rule for splice junctions of nuclear
      mRNA introns from higher eukaryotes but lacks the pyrimidine stretch usually
      found in the immediate vicinity of the 3' splice junction. The structure of the
      intron and the fact that it is found together with the well described self
      splicing rRNA intron is discussed in relation to the evolution of RNA splicing.

PMID- 16453717
TI  - In situ hybridization of immunoglobulin-specific RNA in single cells of the B
      lymphocyte lineage with radiolabelled DNA probes.

PMID- 16453718
TI  - Complete sequence and transcript regulation of a cell adhesion protein from
      aggregating Dictyostelium cells.
AB  - [This corrects the article on p. 1474 in vol. 5.].

PMID- 16453716
TI  - The three-dimensional structure of alpha1-purothionin in solution: combined use
      of nuclear magnetic resonance, distance geometry and restrained molecular
      dynamics.
AB  - The determination of the three-dimensional solution structure of alpha1
      purothionin using a combination of metric matrix distance geometry and restrained
      molecular dynamics calculations based on n.m.r. data is presented. The
      experimental data comprise complete sequence-specific proton resonance
      assignments, a set of 310 approximate interproton distance restraints derived
      from nuclear Overhauser effects, 27 O backbone torsion angle restraints derived
      from vicinal coupling constants, 4 distance restraints from hydrogen bonds and 12
      distance restraints from disulphide bridges. The average atomic rms difference
      between the final nine converged structures and the mean structure obtained by
      averaging their coordinates is 1.5 +/- 0.1 a for the backbone atoms and 2.0 +/-
      0.1 a for all atoms. The overall shape of alpha1-purothionin is that of the
      capital letter L, similar to that of crambin, with the longer arm comprising two
      approximately parallel alpha-helices and the shorter arm a strand and a mini anti
      parallel beta sheet.

PMID- 16453719
TI  - Splicing of an intervening sequence from hybrid cauliflower mosaic viral RNA.
AB  - A DNA sequence encompassing intervening sequence 2 of the soybean leghemoglobin
      gene was inserted into the cauliflower mosaic virus (CaMV) genome. Upon passage
      through host plants progeny virus slowly accumulated that had lost the intron,
      apparently by exact splicing of the RNA form of the genome at the exon/intron
      borders. These findings suggest that reverse transcription from (spliced) RNA to
      DNA is a normal step in CaMV replication. S1 nuclease mapping revealed a mixed
      population of unspliced and spliced viral RNAs. The inefficiency of the splicing
      process is discussed.

PMID- 16453721
TI  - A hairpin plastid genome in barley.
AB  - A linear plastid genome of a barley albino plant derived from anther culture has
      been characterized. The monomeric genome is 21 kb long. This molecule has a
      hairpin structure. We discuss the possible origins of this genome.

PMID- 16453720
TI  - Hairpin DNAs of cauliflower mosaic virus generated by reverse transcription in
      vivo.
AB  - Cauliflower mosaic virus (CaMV) is a DNA plant virus which replicates by reverse
      transcription. During our examination of CaMV replication intermediates by 2-D
      gel electrophoresis, we have discovered a population of bizarre linear double
      stranded hairpin DNAs. The largest hairpin is the size of the CaMV genome;
      hairpin loop ends of smaller molecules map to several sites around the genome but
      the open ends are all located close to the origin of reverse transcription at the
      primer binding site. We believe that the hairpin DNAs are generated in vivo by
      reverse transcription of CaMV RNA followed by self-primed second strand
      synthesis. The accumulation of hairpin DNAs in vivo might represent a side
      reaction of the CaMV reverse transcriptase although an essential role for them in
      the virus replication cycle cannot be discounted. The structure of the hairpin
      DNAs provides further evidence for the location of the start site and of the
      polarity of reverse transcription in CaMV.

PMID- 16453722
TI  - A protein specific to mitochondria from S-type male-sterile cytoplasm of maize is
      encoded by an episomal DNA.
AB  - Mitochondria of S-type cytoplasmic male sterile maize contain two linear double
      stranded DNA molecules, S1 and S2. Two open reading frames (ORF1 and ORF2) are
      present in S2 DNA. Fragments from ORF1 were inserted into plasmids to achieve
      expression in Escherichia coli. Cells transformed with recombinant plasmids
      produced mRNA which hybridized with ORF1 and corresponding polypeptides were
      synthesized by in vivo and in vitro systems. Antiserum against a lacZ/S2 fusion
      protein precipitated the anticipated polypeptides from transformed E. coli cells
      and was therefore used to detect homologous peptide sequences in protein
      preparations of mitochondria from different maize cytoplasms. The antiserum
      detected a protein of 125 000 M(r) present in mitochondria from male sterile B73S
      but absent from the fertile B73N cytoplasm.

PMID- 16453723
TI  - Involvement of ras in sexual differentiation but not in growth control in fission
      yeast.
AB  - The function of the ras gene of Schizosaccharomyces pombe has been studied by
      constructing null and activated alleles of this gene. An activated allele (Val
      (12)) inhibits conjugation but has no effect on cell growth, entry into
      stationary phase or sporulation. The phenotype of Val (12) is distinct from that
      caused by elevating the intracellular level of cAMP. This supports the hypothesis
      that ras of fission yeast does not modulate adenylate cyclase in a manner
      analogous to S. cerevisiae RAS. Introduction of a human ras sequence into fission
      yeast cells containing a non-functional null allele of ras restored the sexual
      differentiation process thus indicating that the human sequence can complement S.
      pombe ras. Our data suggest that although ras genes are highly conserved across a
      considerable evolutionary divide, the cellular function of the ras gene product
      varies in different organisms.

PMID- 16453724
TI  - Isolation and characterization of Schizosaccharomyces pombe cutmutants that block
      nuclear division but not cytokinesis.
AB  - By examining cytological phenotypes of 587 temperature-sensitive mutants of the
      fission yeast Schizosaccharomyces pombe, we obtained 18 mutants which cause cell
      division in the absence of nuclear division. By genetic analyses, these novel
      nuclear division arrest mutants can be classified into nine complementation
      groups (designated cut1 - cut9). The cytological phenotype of cut mutants is
      similar but not identical to that of DNA topoisomerase II mutants (top2). The
      cut1 gene was cloned by transformation and shown to complement cut2 as well as
      cut1, indicating a functional relationship between the two genes. The cut genes
      are required for nuclear division, but their mutant phenotypes differ from most
      of the previously identified mutants which block nuclear division and also the
      subsequent cytokinesis. Fluorescence microscopy indicates that the mitotic
      chromosomes formed in cut mutant cells are abnormal and fail to separate
      properly. We suggest that cut mutations, like top2, block mitotic chromosome
      formation and concomitantly nuclear division, but that cytokinesis proceeds
      independently of the defects in nuclear division, demonstrating uncoordinated
      mitotic pathways. A novel mutant nuc1 is also described which shows a cytological
      phenotype similar to the double mutant of DNA topoisomerases I and II but
      contains normal levels of both DNA topoisomerase activities.

PMID- 16453725
TI  - The cdc22 gene of Schizosaccharomyces pombe encodes a cell cycle-regulated
      transcript.
AB  - Two independent DNA sequences, of 5.6 and 2.4 kb in size, were isolated from
      Schizosaccharomyces pombe gene libraries on the basis of their ability to rescue
      the temperature-conditional lethality conferred by a cdc22 mutation. Integration
      of these sequences into the S.pombe genome by homologous recombination, followed
      by genetic mapping, demonstrated that the site of integration of the 5.6 kb
      fragment is tightly linked to the cdc22 locus, while that of the 2.4 kb fragment
      is unlinked. This shows that the 5.6 kb fragment carries the authentic cdc22 gene
      while the 2.4 kb fragment carries and extragenic suppressor sequence. The cdc22
      transcript was identified by Northern blot analysis and shown to be 3.3 kb in
      size. The level of the transcript during the cell cycle was investigated in
      synchronous cultures prepared by elutriation. The cdc22 transcript is cell cycle
      regulated, reaching a maximum level during late G1/S phase, at least 12-fold
      higher than the minimum level observed in mid G2.

PMID- 16453727
TI  - Timing of initiation of chromosome replication in individual Escherichia coli
      cells.
AB  - [This corrects the article on p. 1711 in vol. 5, PMID: 3527695.].

PMID- 16453726
TI  - The distribution of positively charged residues in bacterial inner membrane
      proteins correlates with the trans-membrane topology.
AB  - The amino acid distribution in membrane spanning segments and connecting loops in
      bacterial inner membrane proteins was analysed. The basic residues Arg and Lys
      are four times less prevalent in periplasmic as compared to cytosolic connecting
      loops, whereas no comparable effect is observed for the acidic residues Asp and
      Glu. Also, Pro is shown to be tolerated to a much larger extent in membrane
      spanning segments with their N-terminus pointing towards the cytosol than in
      those with the opposite orientation. The significance of these findings with
      regard to the mechanism of biogenesis of bacterial inner membrane proteins is
      discussed.

PMID- 16453728
TI  - Full-length von Willebrand factor (vWF) cDNA encodes a highly repetitive protein
      considerably larger than the mature vWF subunit.
AB  - [This corrects the article on p. 1839 in vol. 5, PMID: 3019665.].

PMID- 16453730
TI  - Molecular analysis of two phytohemagglutinin genes and their expression in
      Phaseolus vulgaris cv. Pinto, a lectin-deficient cultivar of the bean.
AB  - Phytohemagglutinin (PHA), the seed lectin of the common bean, Phaseolus vulgaris,
      is encoded by two highly homologous, tandemly linked genes, dlec1 and dlec2,
      which are coordinately expressed at high levels in developing cotyledons. Their
      respective transcripts translate into closely related polypeptides, PHA-E and PHA
      L, constituents of the tetrameric lectin which accumulates at high levels in
      developing seeds. In the bean cultivar Pinto UI111, PHA-E is not detectable, and
      PHA-L accumulates at very reduced levels. To investigate the cause of the Pinto
      phenotype, we cloned and sequenced the two PHA genes of Pinto, called Pdlec1 and
      Pdlec2, and determined the abundance of their respective mRNAs in developing
      cotyledons. Both genes are more than 90% homologous to the normal PHA genes found
      in other cultivars. Pdlec1 carries a 1-bp frameshift mutation close to the 5' end
      of its coding sequence. Only very truncated polypeptides could be made from its
      mRNA. The gene Pdlec2 encodes a polypeptide, which resembles PHA-L and its
      predicted amino acid sequence agrees with the available Pinto PHA amino acid
      sequence data. Analysis of the mRNA of developing cotyledons revealed that the
      Pdlec1 message is reduced 600-fold, and Pdlec2 mRNA is reduced 20-fold with
      respect to mRNA levels in normal cultivars. A comparison of the sequences which
      are upstream from the coding sequence shows that Pdlec2 has a 100-bp deletion
      compared to the other genes (dlec1, dlec2 and Pdlec1). This deletion which
      contains a large tandem repeat may be responsible for the low level of expression
      of Pdlec2. The very low expression of Pdlec1 is as yet unexplained.

PMID- 16453731
TI  - The sequence of carnation etched ring virus DNA: comparison with cauliflower
      mosaic virus and retroviruses.
AB  - Carnation etched ring virus (CERV) DNA comprises 7932 bp. CERV primer binding
      sites and overall genome organization are similar to those of the related
      cauliflower mosaic virus (CaMV). The six open reading frames of CERV showed amino
      acid homology (50-80%) with CaMV ORFs I-VI; no homologues of CaMV ORFs VII or
      VIII were found. CERV ORFs 1-5 interface each other with the sequence ATGA. The
      comparison of CERV ORF5 with CaMV ORFV highlighted regions which show homologies
      to retrovirus gag/pol protease, RNase H and DNA polymerase domains; the
      possibility that the DNA polymerase domain comprises two subdomains, operating
      off different templates, is discussed. Both CERV and CaMV ORFs I have sequence
      homology to tobacco mosaic virus P30 and plastocyanin.

PMID- 16453732
TI  - Localization of the Antennapedia protein in Drosophila embryos and imaginal
      discs.
AB  - Antibodies have been raised against a fusion protein containing the 3' region of
      the coding sequence of the Antennapedia (Antp) gene fused to beta-galactosidase.
      The distribution of the protein on whole mount embryos and imaginal discs of
      third instar larvae was examined by immunofluorescence. In young embryos,
      expression of the Antp protein was limited to the thoracic segments in the
      epidermis, whereas it was found in all neuromeres of head, thorax and abdomen. At
      the end of embryogenesis, the Antp protein mainly accumulated in the ventral
      nervous system in certain parts of the thoracic neuromeres, from posterior T1 to
      anterior T3, with a gap in posterior T2. Comparison of Antp protein distribution
      in nervous systems from wild-type and Df P9 embryos, lacking the genes of the
      Bithorax-complex (BX-C), revealed a pattern of expression which indicated that
      the BX-C represses Antp in the posterior segments with the exception of the last
      abdominal neuromeres (A8-9) which are regulated independently. The protein
      pattern in nervous systems from Sex combs reduced(Scr) mutant embryos was
      indistinguishable from that found in wild-type embryos; thus, neurogenic
      expression of Antp in T1 and the more anterior segments does not appear to be
      under the control of Scr. All imaginal discs derived from the three thoracic
      segments express Antp protein. The distribution was distinct in each disc;
      strongest expression was observed in the proximal parts of the discs. In the leg
      discs the protein distribution seemed to be compartmentally restricted, whereas
      in the wing disc this was not the case. Antp protein was not detected in the eye
      antennal disc. In embryos, as well as in imaginal discs, the protein is localized
      in the nucleus.

PMID- 16453733
TI  - suc1 is an essential gene involved in both the cell cycle and growth in fission
      yeast.
AB  - The gene suc1 encodes a product which suppresses certain temperature sensitive
      mutants of the cell cycle control gene cdc2 of Schizosaccharomyces pombe. Mutants
      in the suc1 gene or over-expression of its product leads to delays in mitotic and
      meiotic nuclear division. Deletion of the suc1 gene is lethal and generates some
      cells blocked in the cell cycle and others impaired in cellular growth. It is
      likely that the suc1 gene product binds and forms unstable complexes with the
      cdc2 protein kinase and with other proteins necessary for the cell cycle and
      cellular growth. suc1 may have a regulatory role in these processes.

PMID- 16453734
TI  - Functional analysis of the yeast plasmid partition locus STB.
AB  - Derivatives of the yeast 2mu plasmid with the cis-acting locus STB (also called
      REP3) are stably maintained if two plasmid-encoded proteins are present in trans.
      There are conflicting reports of both the extent of STB and its possible
      involvement in plasmid partition or copy number control. We have resolved the
      controversy by constructing 2micro derivatives with a conditional STB function,
      and showing that when STB is inactivated plasmids become concentrated in a small
      fraction of the population although the total number of plasmids remains
      unaltered. Moreover we show that STB consists of two functionally distinct
      domains which we call STB-proximal and STB-distal relative to the origin of
      replication. Although STB-proximal is sufficient for proper partitioning, this
      function is severely disrupted by active transcription from neighbouring
      sequences. STB-distal is important to protect STB-proximal and ORI from such
      transcription, and can be effeciently replaced by a 94-bp terminator fragment in
      an orientation-dependent manner. We find that STB-distal contains an additional
      element which depresses transcription from upstream promoters. We also describe
      the phenomenon of replicaton inhibition which we believe can exlain the anomalous
      instability of some yeast plasmids.

PMID- 16453735
TI  - A negative transcriptional control element located upstream of the murine c-myc
      gene.
AB  - [This corrects the article on p. 899 in vol. 5, PMID: 3013622.].

PMID- 16453736
TI  - Reconstitution of beta1-adrenoceptor-dependent adenylate cyclase from purified
      components.
AB  - [This corrects the article on p. 1509 in vol. 5, PMID: 3017696.].

PMID- 16453737
TI  - Molecular characterization of a meiotic recombinational hotspot enhancing
      homologous equal crossing-over.
AB  - [This corrects the article on p. 2123 in vol. 5, PMID: 3023057.].

PMID- 16453738
TI  - Three-dimensional structure of ribulose-1,5-bisphosphate carboxylase/oxygenase
      from Rhodospirillum rubrum at 2.9 A resolution.
AB  - The three-dimensional structure of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum has been determined at
      2.9 A resolution by X-ray crystallographic methods. The MIR-electron density map
      was substantially improved by two-fold non-crystallographic symmetry averaging.
      The polypeptide chains in the dimer were traced using a graphics display system
      with the help of the BONES option in FRODO. The dimer has approximate dimensions
      of 50 x 72 x 105 A. The enzyme subunit is a typical two-domain protein. The
      smaller, N-terminal domain consists of 137 amino acid residues and forms a
      central, mixed five-stranded beta-sheet with alpha-helices on both sides of the
      sheet. The larger C-terminal domain consists of 329 amino acid residues. This
      domain has an eight-stranded parallel alpha/beta barrel structure as found in
      triosephosphate isomerase and a number of other functionally non-related
      proteins. The active site in Rubisco determined by difference Fourier techniques
      and fitting of active site residues to the electron density map, is located at
      the carboxy-end of the beta-strands in the alpha/beta barrel of the C-terminal
      domain. There are few domain-domain interactions within the subunit. The
      interactions at the interface between the two subunits of the dimer are tight and
      extensive. There are tight contacts between the two C-terminal domains, which
      build up the core of the molecule. There are also interactions between the N
      terminal domain of one subunit and the C-terminal domain of the second subunit,
      close to the active site.

PMID- 16453739
TI  - Expression of the ribulose-1,5-bisphosphate carboxylase large subunit gene and
      three small subunit genes in two cell types of maize leaves.
AB  - Transcripts of three distinct ribulose-1,5-bisphosphate carboxylase (RuBPC) small
      subunit (SS) genes account for approximately 90% of the mRNA for this protein in
      maize leaves. Transcripts of two of them constitute >80% of the SS mRNA in 24-h
      greening maize leaves. The third gene contribute approximately 10%. Transcripts
      of all three nuclear-encoded SS genes are detectable in bundle sheath (BSC) and
      mesophyll cells (MC) of etiolated maize leaves. The level of mRNA for each gene
      is different in etioplasts of MC but all drop during photoregulated development
      of chloroplasts in MC and follow a pattern of transitory rise and fall in BSC.
      The amounts of LS and SS proteins continue to increase steadily well after the
      mRNA levels reach their peaks in BSC. The molar ratio of mRNA for chloroplast
      encoded RuBPC large subunit (LS) to the nuclear genome encoded SS is about 10:1
      although LS and SS proteins are present in about equimolar amounts.

PMID- 16453740
TI  - The virulent satellite RNA of turnip crinkle virus has a major domain homologous
      to the 3' end of the helper virus genome.
AB  - RNA C (355 bases), RNA D (194 bases) and RNA F (230 bases) are small, linear
      satellite RNAs of turnip crinkle virus (TCV) which have been cloned as cDNAs and
      sequenced in this study. These RNAs produce dramatically different disease
      symptoms in infected plants. RNA C is a virulent satellite that intensifies virus
      symptoms when co-inoculated with its helper virus in turnip plants, while RNA D
      and RNA F are avirulent. RNA D and RNA F, the avirulent satellites, are closely
      related to each other except that RNA F has a 36-base insert near its 3' end, not
      found in RNA D. The 189 bases at the 5' end of RNA C, the virulent satellite, are
      homologous to the entire sequence of RNA D. However, the 3' half of RNA C, is
      composed of 166 bases which are nearly identical to two regions at the 3' end of
      the TCV helper virus genome. Hence, the virulent satellite is a composite
      molecule with one domain at its 5' end homologous to the other avirulent
      satellites and another domain at its 3' end homologous to the helper virus
      genome. All four TCV RNAs, RNAs C, D and F and the helper virus genome have
      identical 7 bases at their 3' ends. The secondary structure of RNA C deduced from
      the sequence can be folded into two separate domains - the domain of helper virus
      genome homology and the domain homologous to other TCV satellite RNAs.
      Comparative sequences of several different RNA C clones reveal that this
      satellite is a population of molecules with sequence and length heterogeneity.

PMID- 16453741
TI  - Caffeine and heat shock induce adenylate cyclase in Dictyostelium discoideum.
AB  - When vegetative cells of Dictyostelium discoideum were incubated in nutrient
      medium containing 5 mM caffeine, adenylate cyclase was induced and exceeded
      control values 30-fold after 6 h of incubation. The effect was dose-dependent and
      blocked by cycloheximide. Contact site A, a developmentally regulated membrane
      glycoprotein characteristic of aggregation-competent cells, was not induced by
      the treatment. The expression of a developmentally regulated gene coding for an
      unknown protein and hybridizing with the cDNA clone P26E8 was also stimulated,
      indicating that the regulation of expression occurs at the transcript level.
      Cells pretreated with caffeine in growth medium, washed and developed in
      starvation buffer showed an acceleration of development by 2 h as judged by
      stream formation and the appearance of contact sites A. The same effects were
      observed when cells were incubated under heat shock conditions (30 degrees C).
      The results indicate that caffeine stimulates the expression of devevelopmentally
      regulated early genes, and that their products, together with exogeneous
      factor(s), initiate subsequent steps of development.

PMID- 16453743
TI  - The regulation of male-specific transcripts by sex determining genes in
      Drosophila melanogaster.
AB  - The accumulation of male-specific transcripts in various genotypes of Drosophila
      melanogaster was analysed by Northern blot hybridization. The genotypes were
      either hetero- or homozygous for a mutation in one of the genes for somatic sex
      determination. The aim was to study the role of these genes in regulating male
      specific transcription in soma or germ line. All intersexual phenotypes and
      pseudomales irrespective of their genotypic sex accumulate the male-specific
      somatic RNA demonstrating that it is regulated by these genes. In contrast to
      this, the transcript from the male germ line could only be detected in those
      mutant genotypes that have the male sex chromosome constitution of X/Y, although
      its synthesis is not dependent on the presence of a Y chromosome. It is,
      therefore, not under the control of the sex determining loci but directly
      regulated by the primary signal for sex determination, namely the ratio of X
      chromosomes to autosomes.

PMID- 16453742
TI  - Nerve growth factor activates Thy-1 and neurofilament gene transcription in rat
      PC12 cells.
AB  - The effect of nerve growth factor (NGF) on the expression of neurofilament and
      Thy-1 genes in rat PC12 pheochromocytoma cells was examined at both the
      transcriptional and post-transcriptional levels. Addition of NGF to cultured PC12
      cells produced increases in mRNAs corresponding to the 68 kd neurofilament
      protein (NF68) and the Thy-1 glycoprotein within 24 h, with maximal effects of
      some 90- and 45-fold stimulation (relative to beta-actin mRNA) being observed
      after 12 and 4 days of treatment, respectively. In addition, transcriptional run
      off analyses using isolated nuclei showed that NGF treatment resulted directly in
      8- and 4-fold increases in the rate of NF68 and Thy-1 gene transcription. These
      gene activation events were independent of overt morphological differentiation of
      PC12 cells occurring both under conditions permissive and non-permissive for
      neurite outgrowth, and once established the new molecular phenotype was dependent
      upon the continued presence of NGF. This is the first molecular evidence for the
      reversible activation of neuron-specific genes during NGF-induced differentiation
      in PC12 cells.

PMID- 16453744
TI  - The structure of hobo transposable elements and their insertion sites.
AB  - The hobo transposable elements of Drosophila form a family of 3.0-kb elements and
      their deletion derivatives. Their distribution is consistent with the model that
      3.0-kb elements are functionally complete but that smaller hobos are defective
      and require complete elements in trans for transposition. The sequence of one 3.0
      kb element is presented; it has several interesting features, including a 1.9-kb
      open reading frame downstream from potential TATA and CAT sequences. Comparison
      of 11 independent insertion sites shows that in every case the hobo element has
      integrated at and duplicated either the sequence NNNNNNAC or CTTTNNNN. There is
      evidence that an eight nucleotide sequence internal to hobo that matches both of
      these sequences has been used as an insertion site for a second hobo element, as
      the first step in the creation of an internal deletion derivative. Structural
      similarities between hobo and the eukaryotic transposable elements P, Ac, 1723,
      and Tam3, found in widely divergent host organisms, suggest that they all
      transpose by a common mechanism.

PMID- 16453746
TI  - Primary structure of a developmentally regulated nicotinic acetylcholine receptor
      protein from Drosophila.
AB  - [This corrects the article on p. 1503 in vol. 5.].

PMID- 16453745
TI  - Electron microscopic study of DNA complexes with proteins from the
      Archaebacterium Sulfolobus acidocaldarius.
AB  - DNA-protein complexes formed in vitro with isolated DNA-binding proteins from the
      thermoacidophilic archaebacterium Sulfolobus acidocaldarius were analyzed by
      electron microscopy. Two of the proteins (10a and 10b) formed specific structures
      after incubation with DNA. Protein 10a, at low protein concentrations, showed
      individual small spots on the DNA and at high concentrations evenly covered
      doublestranded DNA. Protein 10b showed three different types of regular
      structures: one with single-stranded and two with double-stranded DNA. Using
      double-stranded DNA, 10b first bound cooperatively to two strands forming long,
      plait-like structures only slightly shorter than respective free DNA. The complex
      consists of two right-handed, interwound fibers, with a helical pitch of 26 nm
      and a diameter of approximately 10-11 nm. At higher protein concentration than
      needed to package all DNA into the complex with two double-stranded DNAs, the two
      DNAs were separated again and a new structure was formed evenly covering only one
      DNA strand. Both structures showed no significant contraction of the length of
      the DNA covered in the complex. Nucleoprotein formed with single-stranded PhiX174
      DNA had a diameter of approximately 11 nm and could form circles with a contour
      length of 0.5 mum.

PMID- 16453747
TI  - Identification of a DNA sequence element required for efficient expression of a
      developmentally regulated and cAMP-inducible gene of Dictyostelium discoideum.
AB  - The cysteine proteinase 2 gene of Dictyostelium encodes a developmentally
      regulated sulphydryl proteinase which is first expressed late during cellular
      aggregation. The mRNA is slightly enriched in pre-stalk over pre-spore cells but
      we show here that it is expressed at a somewhat higher level in mature spore
      cells than in stalk cells. The mRNA is induced to accumulate precociously in
      response to exogenous cAMP and we show that a fragment of DNA containing 921
      nucleotides upstream of the major start site of transcription directs regulated
      expression of the gene. Approximately 200 nucleotides upstream of the cap site
      there are two, adjacent, homologous G-rich regions of 9 nucleotides in length. We
      have constructed small internal deletions and point mutations which affect the
      distal element. We find a major reduction in regulated transcription indicating
      this element to be important in mediating cAMP induction of gene expression.

PMID- 16453748
TI  - Molecular analysis of the dominant homeotic Antennapedia phenotype.
AB  - Most of the dominant alleles of the homeotic gene Antennapedia (Antp) which show
      a transformation of antennae into legs are associated with large chromosomal
      inversions. To determine the molecular mechanisms underlying the dominant
      phenotype, one of the strongest Antp alleles (Antp) was studied in more detail.
      The mutant chromosome has been cloned and the structure of the inversion has been
      identified. The inversion breaks two genes apart: the Antp gene and a previously
      unidentified gene, tentatively called responsible for dominant phenotype (rfd),
      located at 84D1-2. The two genes are transcribed in opposite directions and the
      breakpoints lie within introns of both genes. Through the inversion event, a
      reciprocal exchange of the first exons including promoters occurred leading to
      the production of new transcripts. The transcripts containing the entire Antp
      protein coding region which have been fused to the promoter of the rfd gene are
      lost in revertants of the dominant phenotype indicating a correlation between
      this fusion gene and the dominant phenotype. The molecular structure of inversion
      Antp suggests that the dominant phenotype arises via ectopic expression of the
      normal Antp protein due to a gene fusion event.

PMID- 16453749
TI  - Developmental regulation by an enhancer from the Sgs-4 gene of Drosophila.
AB  - A cis acting regulatory region has previously been identified 300-500 bp upstream
      of the Drosophila glue protein gene, Sgs-4. The functional capabilities of this
      region have now been examined by fusing it to the Drosophila Adh gene and
      determining the pattern of expression from the fused construct after
      transformation. The results show that the Sgs-4 sequences between -150 and -568
      are able to direct Adh expression in late third-instar salivary glands, the
      appropriate tissue and timing for Sgs-4 expression. In addition, the Sgs-4
      sequence elevates Adh expression in the anterior midgut and fat body, despite the
      fact that Sgs-4 is not normally expressed there. All three regulatory activities,
      tissue specificity, timing and enhancement, show the positional flexibility of
      enhancer elements. In addition, the Sgs-4 and Adh regulatory elements combine to
      direct expression in novel spatial/temporal combinations in which neither would
      normally be expressed.

PMID- 16453750
TI  - In vitro expression of a full-length DNA copy of cowpea mosaic virus B RNA:
      identification of the B RNA encoded 24-kd protein as a viral protease.
AB  - Double-stranded cDNA was synthesized from B component RNA of cowpea mosaic virus
      and cloned into appropriate vectors. Using four clones, together representing the
      entire B RNA sequence, a full-length DNA copy was constructed and subsequently
      positioned downstream of a phage SP6 or T7 promoter. RNA molecules transcribed
      from this full-size DNA copy using SP6 or T7 RNA polymerase were efficiently
      translated in rabbit reticulocyte lysates into a 200-kd polypeptide similar to
      RNA isolated from viral B components. Moreover this polypeptide was rapidly
      cleaved into 32-kd and 170-kd polypeptides, exactly like the 200-kd polypeptide
      encoded by viral B RNA. In vitro transcription and translation of a DNA copy in
      which an 87-bp-long deletion in the coding sequence for the 24-kd polypeptide was
      introduced revealed that the 24-kd polypeptide bears the proteolytic activity
      involved in the primary cleavage of the B RNA-encoded polyprotein.

PMID- 16453751
TI  - Structural transition in inactive Balbiani ring chromatin of Chironomus during
      micrococcus nuclease digestion.
AB  - We have analysed by micrococcus nuclease digestion the chromatin structure of
      genes in the Balbiani ring (BR) regions of a Chironomus cell line. Gel
      electrophoresis of the DNA fragments reveals a repeating structure which consists
      of two repeat sizes, a long repeat seen in the large fragments and a small repeat
      seen in the small fragments. The two repeats hardly overlap, except in a narrow
      transition zone which is at a different fragment size in the BR 2.2 and the BR
      2.1 gene. The sizes of the large repeats fit the repeat of the underlying DNA
      sequence. The short repeats are between 170 and 180 bp, and after H1 depletion
      the short repeat in the BR 2.2 gene is 160 bp. Our most favoured interpretation
      of these data is that in intact chromatin the nucleosomes in the BR genes are
      phased with respect to the repeating DNA sequence, whereas micrococcus nuclease
      digestion leads to loss of a nucleosome-positioning constraint and hence to
      rearrangement of the nucleosomes. Our results imply a possible artefact of
      nuclease digestion of chromatin, which has to be taken into account in mapping
      nucleosome positions.

PMID- 16453752
TI  - Developmental and molecular analysis of Deformed; a homeotic gene controlling
      Drosophila head development.
AB  - The characteristic morphology of many elements of the Drosophila body plan is
      crucially dependent upon the proper spatial expression of homeotic selector
      genes. The Deformed locus, which we isolated by virtue of its homology to the
      homeo box, is a candidate for a homeotic selector in the head region of the
      developing embryo. Here we show that null mutants of Deformed result in a loss of
      pattern elements derived from the maxillary and mandibular segments, and a
      duplication of a cuticular element of the larval head skeleton. Molecular
      analysis of the locus shows that Dfd transcripts are encoded in five exons
      distributed over 11 kb. The major transcript of 2.8 kb contains a 1758-bp open
      reading frame that would translate to yield a 63.5-kd protein containing a homeo
      domain and conspicuous regions of monotonic amino acid sequences. The Dfd protein
      exhibits extensive homology to a protein encoded by a Xenopus homeo box gene,
      Xhox 1A, suggesting that the Xenopus gene is the frog homologue of Dfd.

PMID- 16453754
TI  - Oocyte-specific transcription of fs(1)K10: a Drosophila gene affecting dorsal
      ventral developmental polarity.
AB  - The expression of the fs(1)K10 gene is required in early oogenesis for the
      establishment of the dorsal-ventral polarity of the oocyte, and later in the
      embryo. P-element-mediated transformation shows that the K10 function is located
      within a fragment of DNA of 5 kb, which encodes four RNA species. A major
      transcript of 3.1 kb is likely to be responsible for the K10 function. It is
      abundant in ovaries and in early developing embryos. Thus its expression profile
      corresponds closely to that which could be anticipated from the biological
      characteristics of the mutation. In situ hybridization on ovary sections shows
      that the gene is not only specifically transcribed in the germ line (which is
      consistent with the germ-line dependence of the mutation), but that its
      expression is also cell-specific since it is apparently restricted to the oocyte.

PMID- 16453753
TI  - Temporal and spatial distribution of transcripts from the Deformed gene of
      Drosophila.
AB  - The Deformed gene of Drosophila is necessary for the proper development of
      epidermal pattern elements arising from the maxillary and mandibular segments of
      the head. We find one major transcript (2.8 kb) homologous to Deformed (Dfd)
      probes which is expressed continuously from 3 h of embryogenesis into adulthood.
      Localized transcript accumulation is first detected just prior to the formation
      of the cellular blastoderm in a single circumferential band at about 65-75% egg
      length. The zone of Dfd expression is approximately two segment primordia in
      width. At later stages of embryogenesis, Dfd transcripts accumulate in the
      posterior ectoderm of the mandibular segment, and in the ventro-lateral ectoderm
      of the maxillary segment. Transcripts are also detected in the mesoderm and
      neuromeres of the mandibular and maxillary segments. The distribution of Dfd
      transcripts supports the hypothesis that Dfd functions as a homeotic selector
      gene in the determination of posterior head segments.

PMID- 16453755
TI  - Multiple spacer sequences in the nuclear large subunit ribosomal RNA gene of
      Crithidia fasciculata.
AB  - In Crithidia fasciculata, a trypanosomatid protozoan, the nuclear-encoded ;28S'
      rRNA is multiply fragmented, comprising two large (c and d) and four small (e, f,
      g and j) RNA species. We have determined that the coding sequences for these RNAs
      (and that of the 5.8S rRNA, species i) are separated from one another by spacer
      sequences ranging in size from 31 to 416 bp. Coding and spacer sequences are
      presumably co-transcribed, with excision of the latter during post
      transcriptional processing generating a highly fragmented large subunit (LSU)
      rRNA. Secondary structure modelling indicates that the C. fasciculata LSU rRNA
      complex (seven segments, including 5.8S rRNA) is held together in part by long
      range intermolecular base pairing interactions that are characteristic of
      intramolecular interactions in the covalently continuous LSU (23S) rRNA of
      Escherichia coli. At least one functionally critical region (encompassing the
      alpha-sarcin cleavage site) is contained in a small RNA species (f) rather than
      in one of the two large RNAs. Within a proposed secondary structure model of C.
      fasciculata LSU rRNA, discontinuities between the different segments (created by
      spacer excision) map to regions that are highly variable in structure in
      covalently continuous LSU rRNAs. We suggest that ;rRNA genes in pieces' and
      discontinuous rRNAs may represent an evolutionarily ancient pattern.

PMID- 16453757
TI  - Localization of the Antennapedia protein in Drosophila embryos and imaginal
      discs.
AB  - [This corrects the article on p. 3327 in vol. 5.].

PMID- 16453756
TI  - Histone transcription in cell cycle mutants of fission yeast.
AB  - The level of histone H2B transcripts peak during S-phase of the fission yeast
      Schizosaccharomyces pombe. The pattern of transcript accumulation has been
      monitored in temperature-sensitive mutants which block at different times during
      the cell cycle, at start in G1 where the cell becomes committed to the mitotic
      cycle, in G1 after start, and during S-phase. Cells blocked before start using
      cdc10-129 do not accumulate histone H2B transcripts, but cells blocked after
      start using cdc22-C11 do show accumulation. Transcript levels increase in another
      mutant cdc20-M10 which also blocks in G1. These experiments establish that
      histone H2B transcripts increase in level in preparation for S-phase during late
      G1 before any DNA synthesis. Passage of start begins a sequence of events leading
      to S-phase which includes an increase in histone H2B transcript levels. In the
      cdc20 and cdc22 mutants transcript levels do not decrease normally suggesting
      that the signals which lead to the fall in level are not given in these G1
      arrested cells. The mutants cdc17-K42 (defective in DNA ligase) and cdc24-M38
      block in late S-phase after the DNA content has doubled. Histone H2B transcripts
      increase normally but remain at a high level. In these mutants even though DNA
      content has doubled, the mechanisms which lead to a fall in transcript levels
      appear not to be brought into play.

PMID- 16453758
TI  - Host-specific regulation of nodulation genes in Rhizobium is mediated by a plant
      signal, interacting with the nodD gene product.
AB  - We have identified a nodD gene from the wide host-range Rhizobium strain MPIK3030
      (termed nodD1) which is essential for nodulation on Macroptilium atropurpureum
      (siratro). Experiments with nodA-lacZ gene fusions demonstrate that the MPIK3030
      nodD1 regulates expression of the nodABC genes. Additionally, we used nodC-lacZ
      fusions of Rhizobium meliloti to show that the MPIK3030 nodD1 gene induces
      expression of these fusions by interacting with plant factors from siratro and
      from the non-host Medicago sativa (alfalfa). The R. meliloti nodD genes, however,
      only interact with alfalfa exudate. In line with these results, no
      complementation of MPIK3030 nodD1 mutants could be obtained on siratro with the
      R. meliloti nodD genes, while the MPIK3030 nodD1 can complement nodD mutants of
      R. meliloti on alfalfa. Furthermore, R. meliloti transconjugants harbouring the
      MPIK3030 nodD1 efficiently nodulate the illegitimate host siratro. When compared
      with other nodD sequences, the amino acid sequence of the MPIK3030 nodD1 shows a
      conserved aminoterminus, whereas the carboxy-terminus of the putative gene
      product diverges considerably. Studies on a chimeric MPIK3030/R. meliloti nodD
      gene indicates that the carboxy-terminal region is responsible for the
      interaction with plant factor(s) and may have evolved in different rhizobia
      specifically to interact with plant-host factors.

PMID- 16453759
TI  - Stoichiometric differences in DNA molecules containing the atpA gene suggest
      mechanisms for the generation of mitochondrial genome diversity in maize.
AB  - Four genomic arrangements of the maize mitochondrial atpA gene (encoding the
      alpha subunit of the F(1) ATPase), have been characterized. Most N (fertile) and
      S (male-sterile) cytoplasms contain two atpA arrangements of equal abundance.
      Prolonged exposure of blots of maize mitochondrial DNA probed with atpA-specific
      sequences show that cytoplasms previously reported to lack one of the atpA
      arrangements do contain the second arrangement but at low levels. Similarly,
      restriction fragments containing the atpA gene previously thought unique to male
      sterile S and T cytoplasms are present in low abundance in fertile cytoplasms.
      These observations suggest that fertile and male-sterile cytoplasms of maize may
      be more closely related than previously thought, and suggest possible mechanisms
      to explain the observed mitochondrial genome diversity.

PMID- 16453760
TI  - Expression of a tuber-specific storage protein in transgenic tobacco plants:
      demonstration of an esterase activity.
AB  - A chimaeric gene composed of the 5' upstream region of STLS1, a leaf/stem
      specifically expressed gene from Solanum tuberosum, and the RNA-coding as well as
      the 3' downstream region of patatin, the major storage protein of potato tubers,
      has been transferred into tobacco plants using the Agrobacterium system. The
      introduction of this gene led to a leaf/stem specific expression of a 42-kd large
      protein which immunocrossreacts with patatin antiserum. Only low amounts of
      immunoreacting protein of smaller size could be detected in transgenic tobacco
      leaves indicating that the patatin protein is fairly stable in this heterologous
      environment. The size of the protein as well as the size of the RNA detected in
      transgenic tobacco leaves using a patatin-specific probe indicates that the
      patatin RNA was accurately processed in both leaf and stem tissue of tobacco. The
      expression of the patatin gene led to the appearance of a new esterase activity
      in the transformed tobacco which co-migrated with a protein immunoreacting with
      patatin antiserum. These data therefore demonstrate that patatin in addition to
      serving as a storage protein displays an enzymatic activity.

PMID- 16453761
TI  - Functional analysis of sequences required for transcriptional activation of a
      soybean heat shock gene in transgenic tobacco plants.
AB  - The 5' DNA sequences involved in the thermal inducibility of the soybean heat
      shock gene hs6871 were analysed in transgenic tobacco plants. The transcriptional
      activity of various in vitro generated deletion mutants was examined by Northern
      blot analysis, S1 nuclease mapping and dot-blot hybridization. At least 181 bp
      upstream from the translational start site are sufficient for thermal induction
      at 40 degrees C and correct initiation of transcripts. Full promoter activity
      with the induction of wild-type levels of transcripts requires additional
      upstream sequences contained within 439 bp 5' to the coding sequence. Our results
      suggest that faithful regulation and the generation of high levels of hs6871
      specific mRNA depend on the presence of sequences which show homology to the 14
      bp heat shock consensus element of Drosophila and, in addition, on as yet
      unidentified enhancer-like upstream sequences.

PMID- 16453762
TI  - Glutamine synthetase genes are regulated by ammonia provided externally or by
      symbiotic nitrogen fixation.
AB  - Glutamine synthetase is the key enzyme in the assimilation by plants of reduced
      nitrogen provided from either the soil or fixed symbiotically in association with
      Rhizobium. We have isolated a number of cDNA clones for soybean glutamine
      synthetase (GS) from a nodule-cDNA library, using RNA from polysomes
      immunoprecipitated by GS antibodies. Transcripts corresponding to two clones
      differing in their 3' non-translated sequences were present in both root and
      nodule tissue; however, the concentration in the nodules was several times
      higher. The relative concentrations of these sequences in both tissues is about
      9:1. Availability of ammonium ions [provided as NH(4)NO(3) or (NH(4))(2)SO(4)]
      enhanced the expression of both sequences in root tissue within 2 h, reaching a
      level similar to that in nodules by 8 h, while KNO(3) had no effect during this
      period. When nitrogen fixation was prevented by replacing nitrogen with argon in
      the root environment or when the nodules were formed by a Fix mutant of
      Bradyrhizobium japonicum, the amounts of GS mRNA did not increase over that in
      roots. These experiments, together with the time course of increase in GS mRNA
      transcripts, suggest that the genes encoding cytosolic GS are directly induced by
      the available ammonia.

PMID- 16453763
TI  - Clovers secrete specific phenolic compounds which either stimulate or repress nod
      gene expression in Rhizobium trifolii.
AB  - Rhizobium trifolii mutants containing Escherichia coli lac gene fusions to
      specific nodulation (nod) genes were used to characterise phenolic compounds
      secreted from the roots of white clover (Trifolium repens) plants. These
      compounds either had stimulatory or inhibitory effects upon the induction of the
      nod genes. The stimulatory compounds were hydroxylated flavones and the most
      active compound was 7,4'-dihydroxyflavone. The inhibitory compounds present in
      white clover root exudates were umbelliferone (a coumarin) and formononetin (an
      isoflavone). Transcriptional activation of nod gene promoters in response to
      short exposures (3 h) of 7,4'-dihydroxyflavone was growth phase dependent; cells
      in early log phase were highly responsive to flavone additions in vitro and nod
      gene induction could be detected within 20 min of exposure at 5 x 10 M. Cells in
      other growth phases were generally unresponsive. A 10-fold molar excess of
      umbelliferone to 7,4'-dihydroxyflavone resulted in complete inhibition of nod
      gene induction. Some commercially-obtained flavones were found to have weak
      stimulatory activity but could also inhibit nod gene induction by more effective
      stimulatory compounds. Strong stimulatory and inhibitory compounds all possessed
      a 7-hydroxy moiety and showed other structural similarities. This suggested that
      there was one binding site for these compounds. Because the response to these
      compounds was rapid, we propose that these phenolics act at the bacterial
      membrane or that an active uptake system is involved.

PMID- 16453764
TI  - Expression of alfalfa mosaic virus coat protein gene confers cross-protection in
      transgenic tobacco and tomato plants.
AB  - A chimeric gene encoding the alfalfa mosaic virus (AlMV) coat protein was
      constructed and introduced into tobacco and tomato plants using Ti plasmid
      derived plant transformation vectors. The progeny of the self-fertilized
      transgenic plants were significantly delayed in symptom development and in some
      cases completely escaped infection after inoculated with AlMV. The inoculated
      leaves of the transgenic plants had significantly reduced numbers of lesions and
      accumulated substantially lower amounts of coat protein due to virus replication
      than the control plants. These results show that high level expression of the
      chimeric viral coat protein gene confers protection against AlMV, which differs
      from other plant viruses in morphology, genome structure, gene expression
      strategy and early steps in viral replication. Based on our results with AlMV and
      those reported earlier for tobacco mosaic virus, it appears that genetically
      engineered cross-protection may be a general method for preventing viral disease
      in plants.

PMID- 16453765
TI  - Structure and elicitor or u.v.-light-stimulated expression of two 4-coumarate:CoA
      ligase genes in parsley.
AB  - We have isolated genomic clones encoding 4-coumarate:CoA ligase (4CL), a key
      enzyme of general phenylpropanoid metabolism, and have analysed the structure and
      regulation of the genes contained on these clones. Restriction enzyme and
      sequence analysis indicated that two distinct 4CL genes, Pc4CL-1 and Pc4CL-2, are
      represented on the clones and that additional 4CL genes are not present in
      parsley. Two lines of evidence suggest that each gene is transcriptionally
      activated by both elicitor and u.v. irradiation: cDNA clones corresponding to
      each gene were found in cDNA libraries made with RNA from both elicitor-treated
      and u.v-irradiated cells, and run-off transcripts homologous to a Pc4CL-2
      specific intron probe were induced by both treatments. This induction was about
      half of the induction measured using probes homologous to both genes. The
      transcription initiation sites of both genes were determined. Comparison of the
      nucleotide sequences of the two genes 5' to these sites showed that they are
      highly homologous for several hundred base pairs and that they contain features
      potentially involved in regulation by elicitor and u.v. irradiation.

PMID- 16453767
TI  - The cell envelope of Thermoproteus tenax: three-dimensional structure of the
      surface layer and its role in shape maintenance.
AB  - The sulphur-dependent archaebacterium Thermoproteus tenax has a cylindrical cell
      shape variable in length, but constant in diameter. Its whole surface is covered
      by a regular protein layer (S-layer). The lattice has p6 symmetry and a lattice
      constant of 32.8 nm. The three-dimensional reconstruction from a tilt series of
      isolated and negatively stained S-layer shows a complex mass distribution of the
      protein: a prominent, pillar-shaped protrusion is located at the 6-fold
      crystallographic axis with radiating arms connecting neighbouring hexamers in the
      vicinity of the 3-fold axis. The base vectors of the S-layer lattice have a
      preferred orientation with respect to the longitudinal axis of the cell. The
      layer can be seen as a helical structure consisting of a right-handed, two
      stranded helix, with the individual chains running parallel. Supposing that new S
      layer protein is inserted at lattice faults (wedge disclinations) near the poles,
      growing of the layer would then proceed by moving a disclination at the end of
      the helix. The constant shape of the cell, as well as the particular structure of
      the layer, strongly suggest that this S-layer has a shape-maintaining function.

PMID- 16453766
TI  - Conserved sequence elements in the 5' region of the Ultrabithorax transcription
      unit.
AB  - Clones homologous to the 5' region of the Ultrabithorax gene of Drosophila
      melanogaster have been isolated from D. pseudoobscura, D. funebris and Musca
      domestica. Regions that encode most of the Ubx protein have been sequenced in all
      three of these species, and the 5' upstream region has been sequenced in D.
      funebris to a point 1000 bases upstream of the probable mRNA start site. Here we
      compare these sequences with those described elsewhere for D. melanogaster.
      Deduced amino acid sequences of the Ubx protein show 8% (D. pseudoobscura), 15%
      (D. funebris) and 22% (M. domestica) divergence from D. melanogaster. However,
      these figures mask very different rates of evolution in different regions of the
      protein. A glycine-rich (;hinge') region is conserved in each of these species,
      although its length is variable. Comparison of D. funebris and D. melanogaster
      sequences in the long 5' untranslated leader region of the mRNA, and in the
      region immediately upstream of the start point of transcription, reveals tightly
      conserved elements embedded in an otherwise non-homologous sequence. These
      conserved elements include a 118-bp region that spans the mRNA start site, an
      internally repetitive (TAA)(n) region in the untranslated leader and a short
      repeated motif immediately upstream of the ATG codon that initiates the major
      open reading frame of the Ubx protein. Two other conserved elements were
      identified upstream of the transcription start site; both elements have
      structural features consistent with a role as recognition sites for regulatory
      proteins.

PMID- 16453769
TI  - Altered mitochondrial gene expression in the nonchromosomal stripe 2 mutant of
      maize.
AB  - The genetic and molecular analyses of higher plant mitochondria can be
      facilitated by studying maternally-inherited mutations, such as the
      nonchromosomal stripe (NCS) mutants of maize, that have deleterious effects on
      plant growth. We have previously demonstrated a correlation between specific
      alterations in mitochondrial DNA and the expression of NCS phenotypes. In the
      present studies, the effects of the NCS2 mutation on mitochondrial gene
      expression are evaluated. Proteins synthesized by mitochondria isolated from NCS2
      mutants and from related plants with normal growth have been compared. NCS2
      mitochondria synthesize much reduced amounts of a single polypeptide. Probes
      corresponding to the mitochondrial DNA region altered in NCS2 hybridize to an
      aberrant set of transcripts in NCS2 mitochondria. Transcripts homologous to
      several previously characterized plant mitochondrial genes are similar in NCS2
      and related non-mutant mitochondria.

PMID- 16453768
TI  - Chalcone isomerase cDNA cloning and mRNA induction by fungal elicitor, wounding
      and infection.
AB  - The environmentally regulated synthesis of phenylpropanoid natural products was
      studied by examining the expression of the gene encoding chalcone isomerase
      (CHI). This enzyme catalyzes a step common to the synthesis of flavonoid pigments
      and isoflavonoid phytoalexins. A lambdagt11 library was constructed using mRNA
      from cell cultures of bean (Phaseolus vulgaris L.) treated with fungal elicitor.
      Two positive clones were obtained by screening 10 recombinants with an antiserum
      to purified bean CHI. The identity of the cloned sequences was confirmed by
      hybrid-select translation and the production of antigenic polypeptides from
      transcripts synthesized in vitro. Addition of elicitor to cell cultures resulted
      in the rapid accumulation of CHI mRNA, with maximum levels achieved 3-4 h after
      elicitation. CHI mRNA also accumulated during the natural infection of hypocotyls
      with the fungal pathogen Colletotrichum lindemuthianum, and in mechanically
      wounded hypocotyls. The kinetics of accumulation of CHI mRNA in response to these
      environmental signals were strikingly similar to those of mRNAs encoding two
      other phenylpropanoid pathway enzymes, phenylalanine ammonialyase and chalcone
      synthase. In contrast to the multi-gene families encoding these two enzymes,
      chalcone isomerase is encoded by a single gene which is regulated by several
      environmental stimuli.

PMID- 16453770
TI  - A mitochondrial gene is lost via homologous recombination during reversion of CMS
      T maize to fertility.
AB  - The Texas (T) male sterile cytoplasm of maize is distinguished by a
      mitochondrially synthesized 13-kd polypeptide and a high susceptibility to the
      toxin produced by the fungal pathogen Helminthosporium maydis. Fertile, toxin
      resistant revertants show an altered restriction profile for mitochondrial DNA
      and do not produce the 13-kd polypeptide. Characterization of cosmid clones from
      CMS T maize and a revertant shows that a heavily transcribed open reading frame
      named T-URF13, potentially coding a 13-kd product, is deleted in the revertant
      mitochondria. Six transcripts present in CMS T mitochondria, 4000, 3000, 2000,
      1800, 1500 and 1200 nucleotides in length, are lacking in revertant mitochondria.
      T-URF25, an open reading frame coding for a 25-kd product, lies to the 3' end of
      T-URF13 but is retained in the revertants. T-URF13 and T-URF25 are co-transcribed
      in CMS T mitochondria; in the revertant T-URF25 is present on a 3100-nucleotide
      species. The recombination that caused these changes involved a 127-bp repeated
      sequence. Homologous recombination took place within the central 55 bp of this
      imperfect repeat. Hybridization analysis of DNA and RNA from other revertants
      demonstrates that a similar or identical event has taken place independently in
      these revertants.

PMID- 16453771
TI  - Phenotypic assay for excision of the maize controlling element Ac in tobacco.
AB  - We describe a phenotypic assay designed to detect excision of the maize
      controlling element Ac from a selectable marker gene, neomycin phosphotransferase
      II (NPT II). An NPT II gene which expresses kanamycin resistance in tobacco
      cells, and contains a unique restriction enzyme site in the untranslated leader
      region, was constructed. Ac, or a defective Ac element (Ac big up tri, open), was
      inserted into the leader region of this gene. The transposon insertions
      inactivated the NPT II gene as determined by transient NPT II expression assays.
      The three plasmids were inserted into the T DNA of Agrobacterium tumefaciens Ti
      plasmid vectors, and transferred to tobacco protoplasts. The transformed
      protoplasts were selected with 100 or 200 microg/ml kanamycin. Protoplasts
      transformed by the NPT II gene interrupted by Ac formed 25% as many calli
      resistant to 100 or 200 microg/ml kanamycin as protoplasts transformed by the
      uninterrupted NPT II gene. Protoplasts transformed by the NPT II gene interrupted
      by Ac big up tri, open did not form any calli resistant to 200 microg/ml of
      kanamycin when transformed under similar conditions. Southern blot hybridization
      analyses of seven kanamycin-resistant calli or plants obtained after
      transformation by the NPT II gene interrupted by Ac revealed that in all cases Ac
      had excised, restoring the structure of the NPT II gene. This assay is therefore
      useful to monitor the activity of a transposable element such as Ac and to define
      the regions of this element involved in transposition activity.

PMID- 16453772
TI  - Transcription of transposable element Activator (Ac) of Zea mays L.
AB  - Transcripts of various sizes hybridize to the transposable element Ac of Zea mays
      in most maize lines. A 3.5-kb mRNA with an abundance of 1-3 x 10 of the poly(A)
      RNA, however, is found exclusively in those lines that carry an active Ac. Plants
      with two Ac elements contain slightly more 3.5-kb Ac transcript than those with
      only one Ac. Overlapping cDNA clones spanning most of the message have been
      isolated and sequenced. The 5'-end of the transcript was determined by Northern
      hybridization and S1 mapping. It starts at several sites over a distance of
      nearly 100 bases, contains an AUG-free leader 600-700 nucleotides long, has a
      long open reading frame encoding 807 amino acids and an untranslated 3'-sequence
      of 239 nucleotides. Four introns with a combined length of 654 bases are removed
      from the primary transcript. Radiosequencing of in vitro translation products
      shows that translation of the long open reading frame begins at the first AUG,
      even though it is located in an unfavourable sequence context. The transcript is
      found in all organs investigated, provided an active Ac is present in the stock.

PMID- 16453773
TI  - Transcription and RNA stability are important determinants of higher plant
      chloroplast RNA levels.
AB  - Transcription in lysed barley plastids and Northern slot blot analyses were used
      to determine the relationship between changes in RNA levels and transcription
      during plastid development. Transcription in plastids of 4.5-9-day-old dark-grown
      or illuminated barley seedlings declined up to 10-fold as a function of plant
      age. Decreased transcription of some plastid genes (rbcL, psaA-psaB) was
      paralleled by decreased levels of mRNA. In other cases (16SrDNA, psbA) the
      changes in transcription were not followed by proportional changes in RNA levels
      indicating that RNA stability is important in establishing the amount of plastid
      RNA for these genes. Further analysis showed that transcription of the plastid
      rRNA transcription unit is regulated differently than the transcription of
      protein coding genes such as psbA or rbcL.

PMID- 16453774
TI  - Crystallization of the photosystem I reaction centre.
AB  - The reaction centre of the photosynthetic membrane complex photosystem I (PSI)
      from the thermophilic cyanobacterium Phormidium laminosum was found to
      crystallize under a range of conditions. The crystallization method, which can
      occur in the presence of larger detergent molecules than those used previously
      for the crystallization of membrane proteins, is presented in this report.
      Several crystal forms have been observed, and some of these show birefringence
      and linear dichroism. Optical measurements on crystals thicker than 5 microm were
      severely restricted because of the very high chlorophyll density within the
      crystals, but linear dichroism measurements on thin single crystals were possible
      and the results are presented here. By comparing the data with earlier
      measurements on oriented PSI complexes, a working model for the orientation of
      the PSI complexes within the crystal could be proposed. The PSI reaction centre
      is one of the largest and most complex membrane protein units that have been
      crystallized to date.

PMID- 16453775
TI  - Laminin is structurally conserved in the sea urchin basal lamina.
AB  - The extracellular matrix is involved in the regulation of differentiation and
      morphogenesis. Here we report the identification of a sea urchin embryonic
      extracellular matrix protein by means of a monoclonal antibody BL1 (Mab BL1) and
      the isolation of the protein from basal lamina preparations. In paraffin sections
      of fixed embryos, the antibody can be detected on the basal surfaces of cells
      after the blastula stage. Immunoprecipitation from embryo lysates and salt
      extracts of metabolically labeled basal lamina preparations demonstrates that the
      basal lamina antigen is a large mol. wt protein of approximate mol. wt 10 which
      consists of disulfide-linked subunits of mol. wts 480 000 and 260 000. Electron
      microscopic images show that the Mab BL1 basal lamina antigen is structurally
      related to the vertebrate extracellular matrix protein laminin.

PMID- 16453776
TI  - Molecular cloning of sequences from wingless, a segment polarity gene in
      Drosophila: the spatial distribution of a transcript in embryos.
AB  - In Drosophila the process of segmentation depends on the function of coordinate,
      gap, pair-rule and segment-polarity genes. Mutations in segment-polarity genes
      cause defects in the pattern of every segment. Here the cloning of sequences from
      a segment-polarity gene, wingless, and the in situ localization of a transcript
      in embryos are described. The transcript is first detected in the anterior and
      posterior regions of the blastoderm embryo at cellularization, and accumulates in
      a series of stripes in the extended germ band, one stripe per metameric unit.
      Each stripe is localized to the most posterior cells of each parasegment. The
      signal is predominantly epidermal, and transcript accumulates only transiently in
      the mesoderm and nervous system. This pattern of expression is discussed with
      respect to models of pattern formation in segmental units.

PMID- 16453777
TI  - The structure of the Ultrabithorax promoter of Drosophila melanogaster.
AB  - The sequence of 4118 nucleotides upstream of the putative initiator codon of the
      D. melanogaster Ultrabithorax protein was determined. The transcription
      initiation site for the corresponding mRNA was identified by S1 nuclease mapping
      and primed extension. It appears that all embryonic RNA products that encode the
      first protein exon are initiated approximately one kilobase upstream of the
      initiator methionine, suggesting a unique Ultrabithorax promoter. The unusually
      long mRNA leader is unspliced. Upstream of the initiator codon occur two
      additional methonine codons; the first one is followed by an open reading frame
      encoding a putative polypeptide of 69 amino acids. We discuss the role of the
      leader and 5' flanking sequences with respect to transcriptional and
      posttranscriptional control of Ultrabithorax gene expression.

PMID- 16453778
TI  - A protein product of the Drosophila recessive tumor gene, l (2) giant gl,
      potentially has cell adhesion properties.
AB  - In the fruitfly Drosophila melanogaster the recessive mutation lethal (2) giant
      larvae affects cell growth and cell adhesion properties of neural and imaginal
      disc cells during embryonic and larval development. Here we report the nucleotide
      sequence of a cDNA from one of the two major transcripts of the l (2) gl gene
      containing a 3.5-kb open reading frame. From the deduced amino acid sequence we
      predict a 130-kd protein with certain sequence similarities to proteins with cell
      adhesion properties. We have raised antibodies against bacterial fusion proteins
      encoded by cDNA subfragments. Affinity-purified specific antibodies recognize a
      130-kd protein in wild-type protein extracts and in situ, which is missing in the
      mutant. Localization of the l (2) gl protein in tissue sections indicates that
      the l (2) gl protein is associated with cellular membranes and probably involved
      in cell-cell interaction.

PMID- 16453779
TI  - Expression of alfalfa mosaic virus RNA 4 in transgenic plants confers virus
      resistance.
AB  - Agrobacterium-mediated transfer from a binary vector was used to produce
      transgenic Nicotiana tabacum plants that expressed coat protein of the plant
      virus, alfalfa mosaic virus (AMV). Expression levels of the chimeric gene, which
      was under the control of the cauliflower mosaic virus 19S promoter, were
      determined in primary transformed plants, in the progeny from self-fertilization
      and in the progeny from crosses to normal tobacco. RNA transcripts that were of
      the expected size as well as a protein of the M(r) and antigenicity of AMV coat
      protein accumulated in the transgenic plants. Plants that expressed the highest
      levels of coat protein developed fewer primary infections following inoculation
      with two strains of AMV and developed systemic infection slower than did plants
      that did not express coat protein. Resistance was specifically against virions of
      the AMV strains. AMV RNA and the unrelated virus, tobacco mosaic virus, were as
      infectious on progeny that expressed coat protein as they were on progeny that
      did not. The relationship between the virus resistance expressed by these
      transgenic plants and that observed in virus cross-protection is discussed.

PMID- 16453780
TI  - Purification and immunochemical characterization of a dihydrofolate reductase
      thymidylate synthase enzyme complex from wild-carrot cells.
AB  - An enzyme complex with dihydrofolate reductase (DHFR, E.C.1.5.1.3.) activity was
      purified to apparent homogenity from wild-carrot cells. The complex has a mol. wt
      of 286 kd and contains five polypeptide chains of 95, 70, 50, 45 and 26 kd. The
      DHFR enzyme activity and methotrexate-binding site are on the 45-kd subunit.
      Folate analogs (methotrexate, aminopterin and formylaminopterin) as well as SH
      group inhibitors [p-hydroxymercuribenzoate, 5,5' -dithiobis(2-nitrobenzoic acid),
      or N-ethylmaleimide] inhibit DHFR. Thymidylate synthase (TS, E.C.2.1.1.45)
      activity co-purified with the enzyme complex through each of seven steps and co
      eluted from gel filtration columns with the DHFR activity at the mol. wt of the
      enzyme complex. Further identification of TS within the complex was achieved
      using a Leishmania DHFR-TS antisera which specifically inhibited the carrot TS,
      although it immunoprecipitated both TS and DHFR. Polyclonal antisera, raised
      against and specific for the complex as judged by Ouchterlony double diffusion
      tests and Western blot analysis, inhibited and immunoprecipitated both DHFR and
      TS. The Leishmania antisera also identified the 70-kd polypeptide within the
      purified complex as TS in a Western blot experiment. The functions of the other
      three polypeptides have not yet been established.

PMID- 16453781
TI  - The achaete-scute complex is expressed in neurogenic regions of Drosophila
      embryos.
AB  - The achaete-scute gene complex (AS-C) of Drosophila melanogaster is involved in
      the development of the embryonic central nervous system and the cuticular sensory
      organs of both larva and adult. We have determined the embryonic spatial
      distributions of three transcripts encoded in the achaete, scute alpha and lethal
      of scute regions of the complex. The RNAs are present mainly between the
      blastoderm/early gastrula and the stage of germ band shortening. The patterns of
      expression are complex and evolve rapidly, affecting most or all of the known
      neurogenic regions. Gene expression precedes and is concomitant with the
      histological appearance of precursors of neural cells. These results support a
      role for the AS-C in determination and early differentiation of embryonic neural
      cells.

PMID- 16453782
TI  - Protein translocation across wheat germ microsomal membranes requires an SRP-like
      component.
AB  - Different wheat germ extracts were tested for the presence of membranes capable
      of translocating and processing nascent secretory proteins. One lysate was found
      in which nascent prehuman-placental lactogen (phPL) was translocated and
      processed to mature human placental lactogen (hPL). Processing was found to occur
      concomitant with translocation across membranes. Translocation across the wheat
      germ membrane required a component which is similar to the mammalian signal
      recognition particle (SRP). It bound to DEAE-Sepharose, had a sedimentation
      coefficient of 11S and contained a 7S RNA. In addition to hPL, the plant protein
      zein and the bacterial protein beta-lactamase were translocated across and
      processed by wheat germ membranes. Transport was found to occur only co
      translationally. Our results show that the wheat germ protein translocation
      system is similar to the mammalian one. Unlike the mammalian SRP, the particle
      purified from wheat germ did not arrest elongation of nascent secretory proteins.

PMID- 16453783
TI  - Gene conversion-like mechanisms may generate polymorphism in human class I genes.

PMID- 16453784
TI  - Linear oligomeric potato spindle tuber viroid (PSTV) RNAs are accurately
      processed in vitro to the monomeric circular viroid proper when incubated with a
      nuclear extract from healthy potato cells.
AB  - A nuclear extract for the processing of oligomeric viroid RNA in vitro has been
      prepared from nuclei isolated from healthy potato cells grown in suspension
      culture. Linear RNA molecules containing concatameric units of (+) or (-)
      strands, respectively, of the potato spindle tuber viroid (PSTV) were synthesized
      in vitro with the aid of the SP6 RNA polymerase and used as substrates for
      processing. When oligomeric linear PSTV (+)RNAs are incubated with the nuclear
      extract, monomeric linear molecules are accurately excised from them, and ligated
      to monomeric PSTV (+)RNA circles representing the viroid proper. Oligomeric PSTV
      (-)RNAs are likewise processed but with a much lower efficiency. Viroid
      processing operates although other nucleolytic activities are still present in
      the extract. These results substantiate our previous finding that oligomeric PSTV
      does not process autocatalytically under in vitro conditions where certain
      introns and other RNAs do. This is the first report of an in vitro RNA processing
      system derived from higher plants.

PMID- 16453785
TI  - Structural and transcription analysis of two homologous genes for the P700
      chlorophyll a-apoproteins in Chlamydomonas reinhardii: evidence for in vivo trans
      splicing.
AB  - The two homologous genes for the P700 chlorophyll a-apoproteins (ps1A1 and ps1A2)
      are encoded by the plastom in the green alga Chlamydomonas reinhardii. The
      structure and organization of the two genes were determined by comparison with
      the homologous genes from maize using data from heterologous hybridizations as
      well as from DNA and RNA sequencing. While the ps1A2 (736 codons) gene shows a
      continuous gene organization, the ps1A1 (754 codons) gene possesses some unusual
      features. The discontinuous gene is split into three separate exons which are
      scattered around the circular chloroplast genome. Exon 1 (86 bp) is separated by
      approximately 50 kb from exon 2 (198 bp), which is located approximately 90 kb
      apart from exon 3 (1984 bp). All exons are flanked by intronic sequences of group
      II. Transcription analysis reveals that the ps1A2 gene hybridizes with a 2.8-kb
      transcript, while all exon regions of the ps1A1 gene are homologous to a mature
      mRNA of 2.7 kb. From our data we conclude that the three distantly separated
      exonic sequences of the ps1A1 gene constitute a functional gene which probably
      operates by a trans-splicing mechanism.

PMID- 16453787
TI  - The sexual inducer of Volvox carteri: purification, chemical characterization and
      identification of its gene.
AB  - The sexual inducer of Volvox carteri f. nagariensis is a glycoprotein and one of
      the most potent biological effector molecules known. It is synthesized by sperm
      cells and converts asexually growing males and females to the sexual pathway.
      Until now, large-scale production of the inducer was made impossible by an
      inherent biological ;switch' mechanism, the spontaneous self-induction of
      asexually growing males. Here we describe a method overcoming this problem for
      the first time. Large-scale production and purification allowed a detailed
      chemical characterization of the inducer with respect to partial amino acid
      sequences and sugar composition. Chemically synthesized oligodeoxynucleotides
      corresponding to derived amino acid sequences were used to screen a genomic gene
      bank of V. carteri HK 10. A positive clone (Ind-28) was shown to encode the
      inducer gene by subcloning and sequencing.

PMID- 16453786
TI  - Amino acid sequence of the cytochrome subunit of the photosynthetic reaction
      centre from the purple bacterium Rhodopseudomonas viridis.
AB  - The complete nucleotide sequence of the gene encoding the cytochrome subunit of
      the photosynthetic reaction centre from the purple bacterium Rhodopseudomonas
      viridis, and the derived amino acid sequence are presented. The nucleotide
      sequence of the gene reveals the existence of a typical bacterial signal peptide
      of 20 amino acid residues which is not found in the mature cytochrome subunit.
      The gene encoding the cytochrome subunit is preceded by the gene encoding the M
      subunit. Both genes overlap by 1 bp. The mature cytochrome subunit consists of
      336 amino acid residues; 73% of its amino acid sequence was confirmed by protein
      sequencing work. The mol. wt of the cytochrome subunit including the covalently
      bound fatty acids and the bound heme groups is 40 500. The internal sequence
      homology is low, despite the symmetric structure of the cytochrome subunit
      previously shown by X-ray crystallographic analysis of the intact photosynthetic
      reaction centre. Sequence homologies to other cytochromes were not found.

PMID- 16453788
TI  - Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase)
      deduced from a complementary DNA.
AB  - [This corrects the article on p. 1317 in vol. 6, PMID: 2440677.].

PMID- 16453789
TI  - Engineering herbicide resistance in plants by expression of a detoxifying enzyme.
AB  - Phosphinothricin (PPT) is a potent inhibitor of glutamine synthetase in plants
      and is used as a non-selective herbicide. The bar gene which confers resistance
      in Streptomyces hygroscopicus to bialaphos, a tripeptide containing PPT, encodes
      a phosphinothricin acetyltransferase (PAT) (see accompanying paper). The bar gene
      was placed under control of the 35S promoter of the cauliflower mosaic virus and
      transferred to plant cells using Agrobacterium-mediated transformation. PAT was
      used as a selectable marker in protoplast co-cultivation. The chimeric bar gene
      was expressed in tobacco, potato and tomato plants. Transgenic plants showed
      complete resistance towards high doses of the commercial formulations of
      phosphinothricin and bialaphos. These data present a successful approach to
      obtain herbicide-resistant plants by detoxification of the herbicide.

PMID- 16453790
TI  - Characterization of the herbicide-resistance gene bar from Streptomyces
      hygroscopicus.
AB  - A gene which confers resistance to the herbicide bialaphos (bar) has been
      characterized. The bar gene was originally cloned from Streptomyces
      hygroscopicus, an organism which produces the tripeptide bialaphos as a secondary
      metabolite. Bialaphos contains phosphinothricin, an analogue of glutamate which
      is an inhibitor of glutamine synthetase. The bar gene product was purified and
      shown to be a modifying enzyme which acetylates phosphinothricin or
      demethylphosphinothricin but not bialaphos or glutamate. The bar gene was
      subcloned and its nucleotide sequence was determined. Interspecific transfer of
      this Streptomyces gene into Escherichia coli showed that it could be used as a
      selectable marker in other bacteria. In the accompanying paper, bar has been used
      to engineer herbicide-resistant plants.

PMID- 16453791
TI  - Cloning of a Nicotiana plumbaginifolia protoplast-specific enhancer-like
      sequence.
AB  - We have isolated a 1.5-kb plant DNA fragment (called insert 7) from Nicotiana
      plumbaginifolia DNA that contains a protoplast-specific enhancer-like sequence.
      The presence of this sequence on a plasmid carrying a chimeric nos-npt-II gene
      conferring kanamycin resistance to plant cells, produces an overexpression of the
      npt-II gene during at least eight days after protoplast transformation. This
      effect on the expression of the nos promoter was independent of the orientation
      and was observed both on circular and linearized plasmids. On the contrary,
      insert 7 had no influence when present on another plasmid (in trans) in
      cotransformation experiments. The overexpression of the nos-npt-II gene due to
      the presence of insert 7 on the transforming plasmid is correlated with a higher
      level of synthesis of the corresponding RNA. Insert 7 did not affect the level of
      expression of the nos-npt-II gene in stably transformed calli, or in regenerated
      plants. However, the overexpression was again detected in protoplasts prepared
      from leaves of stably transformed plants. This 1.5-kb plant DNA fragment contains
      highly repetitive DNA sequences, specific to N. plumbaginifolia. However, the
      enhancer-like activity is localized on a 600-bp unique sequence of insert 7.
      Insert 7 had no detectable effect on the transient expression of another gene,
      the nopaline synthase gene present at a longer distance on the same plasmid.

PMID- 16453792
TI  - Parsley protoplasts retain differential responsiveness to u.v. light and fungal
      elicitor.
AB  - The differential response of cultured parsley cells to u.v. irradiation and
      elicitor treatment is a paradigm for analysis of specific plant defense
      responses. We demonstrate that freshly isolated parsley protoplasts, in the
      absence of detectable cell wall, maintain fully the ability to be activated by
      these important environmental factors. Stimulated protoplasts synthesize typical
      qualitative patterns and amounts of potentially protective flavonoid glycosides
      and coumarin phytoalexins following either u.v. irradiation or treatment with
      fungal elicitor, respectively. Induced accumulation of mRNAs and enzymes of the
      phenylpropanoid biosynthetic pathways is nearly identical in protoplasts and
      cells. Stimulation of protoplasts with elicitor requires only a short period of
      contact, which is not sufficient for cell wall regeneration. Importantly, there
      is no activation of these pathways during protoplast preparation. These results
      establish that parsley protoplasts respond appropriately to two physically
      distinct stimuli and might serve as an especially suitable system for the
      analysis of signal transduction and gene activation.

PMID- 16453794
TI  - Notes added in proof.

PMID- 16453793
TI  - Function of the 30 kd protein of tobacco mosaic virus: involvement in cell-to
      cell movement and dispensability for replication.
AB  - We have investigated the function of the 30 kd protein of tobacco mosaic virus
      (TMV) by a reverse genetics approach. First, a point mutation of TMV Ls1 (a
      temperature-sensitive mutant defective in cell-to-cell movement), that causes an
      amino acid substitution in the 30 kd protein, was introduced into the parent
      strain, TMV L. The generated mutant showed the same phenotype as TMV Ls1, and
      therefore the one-base substitution in the 30 kd protein gene adequately explains
      the defectiveness of TMV Ls1. Next, four kinds of frame-shift mutants were
      constructed, whose mutations are located at three different positions of the 30
      kd protein gene. All the frame-shift mutants were replication-competent in
      protoplasts but none showed infectivity on tobacco plants. From these
      observations the 30 kd protein was confirmed to be involved in cell-to-cell
      movement. To clarify that the 30 kd protein is not necessary for replication, two
      kinds of deletion mutants were constructed; one lacking most of the 30 kd protein
      gene and the other lacking both the 30 kd and coat protein genes. Both mutants
      replicated in protoplasts and the former still produced the subgenomic mRNA for
      the coat protein. These results clearly showed that the 30 kd protein, as well as
      the coat protein, is dispensable for replication and that no cis-acting element
      for replication is located in their coding sequences. It is also suggested that
      the signal for coat protein mRNA synthesis may be located within about 100
      nucleotides upstream of the initiation codon of the coat protein gene.

PMID- 16453795
TI  - The gooseberry-zipper region of Drosophila: five genes encode different spatially
      restricted transcripts in the embryo.
AB  - Genetic analysis of the Drosophila chromosome region 60 E9-F1 identified two
      functions affecting embryonic development; gooseberry (gsb), a segment polarity
      gene, and zipper (zip), an unclassified gene which affects cuticle formation
      severely. By contrast, molecular analysis revealed five genes with different
      temporal and spatial patterns of expression in the embryo. Candidate genes for
      gsb and zip functions were identified. Two adjacent genes are eventually
      expressed in regular stripes within the posterior region of each segment. One of
      them is expressed initially in a pair-rule mode; the second gene expresses
      reduced levels of transcripts in a mutant which leaves the transcribed region and
      the sequences up to the second gene intact. This observation, the patterns of
      transcripts in the embryo and the genetic data suggest that both genes are
      involved in gooseberry segmentation function. zip is expressed in neural tissue
      and not in epidermal anlagen. Embryos lacking zip activity also develop abnormal
      neural tissue consistent with the argument that the zip cuticle phenotype is a
      secondary effect. Additional newly identified genes are expressed in specific
      domains of the embryo, covering mesoderm anlagen and the dorsal region of embryos
      at blastoderm stage, respectively.

PMID- 16453797
TI  - The Nerve Growth Factor: thirty-five years later.
AB  - [This corrects the article on p. 1146 in vol. 6.].

PMID- 16453798
TI  - A protein product of the Drosophila recessive tumor gene, l (2) gl, potentially
      has cell adhesion properties.
AB  - [This corrects the article on p. 1791 in vol. 6.].

PMID- 16453796
TI  - Isolation and analysis of the genes for cytochrome c oxidase in Paracoccus
      denitrificans.
AB  - Synthetic oligonucleotide probes were used to clone two loci from the chromosomal
      DNA of Paracoccus denitrificans that contain the genes for cytochrome c oxidase
      (cytochrome aa(3)). One locus seems to contain four or five genes probably
      forming an operon. Two of these code for the oxidase subunits II and III. Three
      open reading frames are found between the COII and COIII genes. The other locus
      codes for the subunit I. A short open reading frame is found upstream of this
      gene. All three subunits of the Paracoccus enzyme show remarkable homology to the
      corresponding subunits of the mitochondrial cytochrome oxidase. Possible protein
      products of the open reading frames have not yet been identified.

PMID- 16453799
TI  - An insertional mutant of epidermal growth factor receptor allows dissection of
      diverse receptor functions.
AB  - [This corrects the article on p. 2669 in vol. 6, PMID: 2824188.].

PMID- 16453800
TI  - Isolation and nucleotide sequence of mouse NCAM cDNA that codes for a M(r) 79 000
      polypeptide without a membrane-spanning region.
AB  - [This corrects the article on p. 907 in vol. 6, PMID: 3595563.].

PMID- 16453801
TI  - The ocs element: a 16 base pair palindrome essential for activity of the octopine
      synthase enhancer.
AB  - A 176 bp DNA sequence lying upstream of the octopine synthase (ocs) promoter,
      previously shown to have enhancer-like properties in transgenic tobacco [Ellis et
      al. (1987) EMBO J., 6, 11-16], functions as an enhancer in protoplasts of Zea
      mays (a monocot plant) and Nicotiana plumbaginifolia (a dicotplant). We have
      characterized this element by transient expression assays using a linked alcohol
      dehydrogenase (Adh1) promoter from Z. mays and the chloramphenicol
      acetyltransferase coding sequences. The ocs sequence functions in both
      orientations but its enhancing activity is dependent upon its distance from the
      Adh1 promoter. Transient expression assays using deletion mutants and synthetic
      oligonucleotides show that a 16 bp palindrome ACGTAAGCGCTTACGT, contained within
      the 176 bp fragment, is essential and sufficient for enhancing activity in
      transient expression assays.

PMID- 16453802
TI  - Biological function of ;pathogenesis-related' proteins: four PR proteins of
      tobacco have 1,3-beta-glucanase activity.
AB  - Three of the ten acidic ;pathogenesis-related' (PR) proteins known to accumulate
      in Nicotiana tabacum cv Samsun NN reacting hypersensitively to tobacco mosaic
      virus, namely -O, -N and -2, have been shown to have 1,3-beta-glucanase (EC
      3.2.1.39) activity. By using sera raised against each protein purified to
      homogeneity close serological relationships have been demonstrated between the
      three proteins. The same specific sera cross-reacted with a basic protein which
      is also a 1,3-beta-glucanase induced by virus infection and which can be
      considered as a new basic pathogenesis-related protein of tobacco. Protein PR-O
      and the basic 1,3-beta-glucanase display about the same specific enzymatic
      activity, i.e. 50-fold and 250-fold higher than specific activities of proteins
      PR-N and -2 respectively.

PMID- 16453803
TI  - Synthesis and protein body deposition of maize 15-kd zein in transgenic tobacco
      seeds.
AB  - The maize 15-Kd zein structural gene was placed under the regulation of French
      bean beta-phaseolin gene flanking regions. Agrobacterium tumefaciens-mediated
      transformation was used to insert the chimeric phaseolin-zein gene into the
      tobacco genome. Transgenic plants synthesized zein in a tissue-specific manner
      during the latter half of seed development. Transcription of the chimeric gene
      was initiated in phaseolin-derived sequences, and was terminated within the
      phaseolin gene 3' flanking region. Both zein- and phaseolin-derived
      polyadenylation signals were used in the processing of zein RNA in transgenic
      plant seeds. Zein accumulation, though subject to an 80-fold variation among 19
      plants tested, could reach as much as 1.6% of the total seed protein in several
      plants. In developing tobacco seeds, zein was correctly processed by the removal
      of a 20-amino-acid signal peptide. Electron microscope immunogold localization of
      the zein expressed in embryo and endosperm tissue indicates that the monocot
      protein accumulates in the crystalloid component of vacuolar protein bodies. The
      density of gold label over the protein bodies is several fold greater in the
      embryo than the endosperm. Zein is found in roots, hypocotyls and cotyledons of
      germinating transgenic tobacco seeds.

PMID- 16453804
TI  - The molecular basis for rRNA-dependent spectinomycin resistance in Nicotiana
      chloroplasts.
AB  - The chloroplast genes coding for the 16S ribosomal RNA from several spectinomycin
      resistant Nicotiana mutants were analyzed. Two classes of mutants were
      identified. In one class, a G to A base transition is found at position 1140 of
      the tobacco-chloroplast 16S rRNA gene, which eliminates an AatII restriction
      endonuclease site. This base transition is proximal to a mutation previously
      described for spectinomycin resistance in Escherichia coli. In the other class, a
      novel G to A transition is found at position 1012 of the 16S rRNA gene. Although
      the mutations in the two classes are 128 nucleotides apart, the secondary
      structure model for 16S rRNA suggests that the two mutated nucleotides are in
      spatial proximity on opposite sides of a conserved stem structure in the 3'
      region of the molecule. Phylogenetic evidence is presented linking this conserved
      stem with spectinomycin resistance in chloroplasts. Perturbation of the stem is
      proposed to be the molecular-genetic basis for rRNA-dependent spectinomycin
      resistance.

PMID- 16453805
TI  - Molecular organization of the maternal effect region of the Shaker complex of
      Drosophila: characterization of an I(A) channel transcript with homology to
      vertebrate Na channel.
AB  - We have cloned 215-kb DNA containing the maternal effect region (ME) of the
      Shaker gene complex (shC) at 16F of the Drosophila X chromosome. Five
      translocation and deletion breakpoints have been mapped on the cloned DNA
      allowing a correlation of the genetic map to transcription units. The ME region
      spans 100 kb. The genetic behavior of this region correlates with the occurrence
      of maternal RNAs in this part of the ShC. Two transcripts have been identified in
      the vicinity of chromosomal rearrangements which cause a Sh phenotype. These are
      a 4.5-kb transcript interrupted by T(x;2)B27 and a 2-kb transcript interrupted by
      T(X;3)Sh and T(X;Y)W32. The latter transcript is derived from a primary
      transcript which spans >65 kb genomic DNA. The cDNA-sequencing data show that
      this Shaker (I(A)channel) gene can encode a protein of 35 kd with three alpha
      helical membrane-spanning sequences near its carboxyl terminus. These have a
      striking homology with membrane-spanning sequences of the vertabrate Na channel.

PMID- 16453806
TI  - The neurogenic gene Delta of Drosophila melanogaster is expressed in neurogenic
      territories and encodes a putative transmembrane protein with EGF-like repeats.
AB  - The decision of an ectodermal cell to take on a neural or an epidermal fate
      depends on its interactions with the neighbouring cells. In Drosophila
      melanogaster, the available evidence suggests that a regulatory signal necessary
      for epidermal commitment is built by the products of the so-called neurogenic
      genes. We have cloned 180 kb of genomic DNA surrounding the neurogenic gene Delta
      (Dl). Restriction fragment-length polymorphisms were mapped to a region of 25 kb.
      These 25 kb of DNA are assumed to contain essential parts, or all, of the Dl
      gene. Northern blots detect two developmentally regulated transcripts, of 5.4 and
      4.6 kb, which are associated with the region where the mutants map. Serveral cDNA
      clones were recovered from embryonic cDNA libraries by homology to the 25 kb of
      genomic DNA. The complete sequence of a cDNA clone containing an insert of 4.73
      kb was determined. The conceptual translation of the longest open reading frame
      yields a protein of 880 amino acids. This protein displays characteristics of a
      membrane protein, with intercellular, transmembrane and extracellular domains.
      The extracellular domain contains a tandem array of nine EGF-like repeats. In in
      situ hybridizations to tissue sections, transcripts homologous to Dl are detected
      in all territories with neurogenic abilities, e.g. the neurogenic ectoderm and
      the primordia of the sensory organs. Initially all cells of these neurogenic
      territories express Dl, but later on transcription of Dl becomes restricted to
      the cells that have adopted the neural fate. The topological specificity in the
      transcription of Dl corresponds to the one expected for a regulatory signal that
      mediates epidermal commitment.

PMID- 16453807
TI  - Novel expression of the ribosomal RNA genes in the extreme thermophile and
      archaebacterium Desulfurococcus mobilis.
AB  - The single 16S/23S rRNA operon of the sulfur-dependent extreme thermophile
      Desulfurococcus mobilis is transcriptionally uncoupled from the single 5S RNA
      gene. Transcription of the former operon initiates at five sites, P5-P1. RNA
      polymerases intiating at sites P5-P2 terminate and then reinitiate at the next
      downstream site, thus providing a queue of polymerases at the primary initiation
      site P1. Putative promoter sequences that are AT-rich lie upstream from each
      site. Termination occurs at two main sites within long pyrimidine sequences
      downstream from the 23S RNA gene. A processing site for both large RNAs occurs at
      a secondary structural feature common to other archaebacterial rRNAs.
      Transcription of 5S RNA starts mainly at P1/5S at the 5' end of the gene with a
      low level of initiation from two upstream sites; a similar mechanism of
      initiation-termination-reinitiation appears to operate and the sites are all
      preceded by AT-rich promoter-like sequences. Termination occurs a few nucleotides
      beyound the 3' end of the 5S RNA. The mature RNA contains 133 nucleotides, has a
      78% GC bp content and exhibits an unusually extended version of helix I with
      heterogeneous ends. The expression of the rRNA genes shows characteristics of
      eukaryotes, eubacteria and archaebacteria.

PMID- 16453808
TI  - 5' Analysis of the soybean leghaemoglobin lbc(3) gene: regulatory elements
      required for promoter activity and organ specificity.
AB  - The soybean leghaemoglobin lbc(3) gene promoter was analysed in transgenic Lotus
      corniculatus plants. Hybrid-promoter constructions and 5' deletions were studied
      using chimeric genes composed of the various promoters, the chloramphenicol
      acetyltransferase (CAT) coding sequence and the lbc(3) 3' flanking region. A 5'
      Bal31 deletion series mapped a strong positive regulatory element between -1100
      and -950. A weaker element located between -230 and -170 defined the minimum 5'
      region required for detectable promoter activity. Reactivation of inactive
      promoters with deletion endpoints between -230 and the transcription initiation
      site was obtained employing the constitutive cauliflower mosaic virus (CaMV) 35S
      enhancer. The position of cis regulatory element(s) required for nodule-specific
      expression was defined to 37 bp between -139 and -102. This region contains
      sequences conserved in other leghaemoglobin and nodulin genes. No indispensable
      control elements were found on the lbc(3) 3' flanking region.

PMID- 16453809
TI  - Differences in expression between two seed lectin alleles obtained from normal
      and lectin-deficient beans are maintained in transgenic tobacco.
AB  - Using Agrobacterium-mediated transformation, two genes for phytohemagglutinin-L
      (PHA-L), the lectin seed protein of the common bean Phaseolus vulgaris, were
      stably integrated into the tobacco genome. The two alleles for PHA-L, dlec2 and
      pdlec2, were obtained from a normal cultivar (Greensleeves) and a lectin
      deficient cultivar (Pinto) respectively. In the bean embryos, the expression of
      dlec2 is 30 times greater than the expression of pdlec2. In the dlec2-transformed
      tobacco, PHA-L accumulated specifically in the seeds at the same stages as the
      tobacco seed storage proteins and was degraded after germination. PHA-L was found
      in the embryo, and at a 5-7 times lower concentration in the endosperm tissue of
      the mature tobacco seeds. No PHA could be detected in other parts of the plants.
      We conclude that the signals for temporal and spatial regulation of the dlec2
      gene are present in the DNA fragment used for transformation. Transformation with
      the second PHA-L allele pdlec2 from the cultivar Pinto caused the accumulation of
      about 50 times less PHA-L in tobacco seeds when compared to dlec2. We conclude
      from analyzing the 5' sequences of dlec2 and Pdlec2 that the low expression
      phenotype of the Pdlec2 allele could be due to the absence or mutation of a cis
      acting element carried by the dlec2 fragment.

PMID- 16453810
TI  - Cytokinin stress changes the developmental regulation of several defence-related
      genes in tobacco.
AB  - Tobacco shoots exposed to elevated endogenous or exogenous cytokinin levels are
      unable to develop roots and lack apical dominance. We have isolated cDNA copies
      of five mRNA species that accumulate to elevated levels in such cytokinin
      stressed shoots via differential screening of a cDNA library of transgenic shoots
      which contain an active T-DNA cytokinin gene (T-cyt gene) from Agrobacterium
      tumefaciens. Four of the cDNA clones were found to correspond to plant defence
      related mRNAs, encoding extensin, chitinase, PR-1 and a PR-1-like protein,
      respectively. In normal tobacco plants PR-1 mRNA is relatively rare in all
      organs. The other four mRNAs occur at relatively low levels in shoots, especially
      in leaves, but are very prevalent in roots. Extensin mRNA, for example, is not
      detectable in leaves, while it is an abundant mRNA in roots and stems. In normal
      shoots cultured on cytokinin-containing medium all five mRNAs accumulate to
      elevated levels, similar to those found in transgenic T-cyt shoots. We conclude
      that the imposed cytokinin stress causes changes in the tissue-specific control
      of the levels of several defence-related mRNA species in tobacco.

PMID- 16453811
TI  - Ornithine carbamoyltransferase genes and phaseolotoxin immunity in Pseudomonas
      syringae pv. phaseolicola.
AB  - Two different DNA fragments encoding ornithine carbamoyltransferase (OCTase) were
      cloned from Pseudomonas syringae pv. phaseolicola NPS3121. These fragments did
      not cross-hybridize and encoded OCTases which differed with respect to their
      sensitivity to purified phaseolotoxin, an OCTase inhibitor produced by this
      phytopathogenic bacterium. Recombinant plasmids carrying these DNA fragments
      complemented OCTase-deficient strains of Escherichia coli and Pseudomonas
      aeruginosa. Extracts of the complemented E. coli strain contained OCTase enzyme
      activities with similar degrees of sensitivity to purified phaseolotoxin as
      extracts of P.s.phaseolicola grown at either 20 or 30 degrees C. The OCTase
      activity detectable in extracts of P.s.phaseolicola grown at 20 degrees C is
      insensitive to phaseolotoxin while that detectable in extracts of cells grown at
      30 degrees C is sensitive to the toxin. E.coli HB101 harboring recombinant
      plasmids carrying the gene(s) encoding the phaseolotoxin-insensitive enzyme
      activity exhibited resistance to purified phaseolotoxin. The results of Tn5
      mutagenesis and Southern blotting and the pattern of complementation of OCTase
      deficient and Tox mutant strains suggest that the gene(s) encoding the
      phaseolotoxin-insensitive OCTase is part of a gene cluster involved in
      phaseolotoxin production.

PMID- 16453812
TI  - Post-translational glycosylation of the contact site A protein of Dictyostelium
      discoideum is important for stability but not for its function in cell adhesion.
AB  - The functions of type 1 and 2 carbohydrates of the contact site A (csA)
      glycoprotein of Dictyostelium discoideum have been investigated using mutants
      lacking type 2 carbohydrate. In two mutant strains, HG220 and HG701, a 68-kd
      glycoprotein was synthesized as the final product of csA biosynthesis. This
      glycoprotein accumulated to a much lower extent on the surfaces of mutant cells
      than the mature 80-kd glycoprotein did in wild-type cells. There was also no
      accumulation of the 68-kd glycoprotein observed within the mutant cells nor was a
      precursor of lower molecular mass detected, in accordance with previous findings
      that indicated cotranslational linkage of type 1 carbohydrate by N-glycosylation.
      Pulse-chase labelling showed that a 50-kd glycopeptide was cleaved off from the
      mutant 68-kd glycoprotein and released into the medium, while the fully
      glycosylated 80-kd glycoprotein of the wild type was stable. These results assign
      a function to type 2 carbohydrate in protecting the cell-surface-exposed csA
      glycoprotein against proteolytic cleavage. HG220 cells were still capable of
      forming EDTA-stable contacts to a reduced extent, consistent with the low amounts
      of the 68-kd glycoprotein present on their surfaces. Thus type 1 rather than type
      2 carbohydrate appears to be directly involved in intercellular adhesion that is
      mediated by the csA glycoprotein. Tunicamycin-treated wild-type and mutant cells
      produce a 53-kd protein that lacks both type 1 and 2 carbohydrates. While this
      protein is stable and not transported to the cell surface in the wild type, it is
      cleaved in the mutants and fragments of it are released into the extracellular
      medium. These results suggest that the primary defect in the two mutants studied
      is relief from a restriction in protein transport to the cell surface, and that
      the defect in type 2 glycosylation is secondary.

PMID- 16453813
TI  - An ecdysone response element in the Drosophila hsp27 promoter.
AB  - It has previously been shown that a region of 100 bp in the Drosophila hsp27
      promoter is sufficient to confer ecdysone inducibility on a heterologous gene. We
      now show, using binding and DNase I footprinting assays, that a 23-bp hyphenated
      dyad within this sequence forms a protein-binding site, and that this is
      sufficient for inducibility. The sequence shows partial homology with mammalian
      steroid receptor binding sites. UV crosslinking identifies an 80- to 90-kd
      protein that binds specifically to this sequence and is thus a candidate for the
      ecdysone receptor.

PMID- 16453814
TI  - Cis-acting sequences sufficient for correct tissue and temporal specificity of
      larval serum protein 1 genes of Drosophila.
AB  - We have constructed hybrid genes in which the coding region of the bacterial gene
      chloramphenicol acetyl transferase (CAT) has been linked to varying lengths of
      upstream sequences of Drosophila genes for larval serum sequence 1 (LSP1). These
      have been inserted into a P-element transformation vector and subsequently
      transferred into the germ-line of recipient flies. Transformants carrying the CAT
      gene linked to 1650 bp, 570 bp or 377 bp of upstream LSP1alpha sequences, or 745
      bp or 471 bp of upstream beta sequences express CAT with the same developmental
      and tissue specificity as the endogenous LSP1 genes. Constructs having only 66 bp
      of upstream LSP1beta sequences, however, show extremely low levels of CAT
      expression in tissues and at developmental stages in which LSP1 is not expressed.
      We discuss the significance of short regions of homology between the DNA upstream
      of the alpha and beta genes, which lie within the regions identified by the
      transformation experiments as being required for the cis-regulation of LSP1
      synthesis.

PMID- 16453815
TI  - Cin4, an insert altering the structure of the A1 gene in Zea mays, exhibits
      properties of nonviral retrotransposons.
AB  - A wild-type allele of the A1 gene of Zea mays contains a 1.1-kb-long insert
      termed Cin4-1, which alters the structure of the transcription unit compared to
      other A1 alleles. The Cin4-1 element is a member of a family of elements
      occurring in 50-100 copies in the maize genome. Genomic cloning and sequence
      analysis of several family members and their flanking regions allowed
      classification of Cin4 as a nonviral retrotransposon. Individual Cin4 elements
      terminate in an oligo(A) track of variable size (6-11 residues) at their 3'-end.
      The 5'-ends of family members are heterogeneously truncated with respect to the
      longest Cin4 element. Cin4 elements are flanked by small direct duplications, the
      size of which varies between 3 and 16 bp. On the basis of a comparison of the
      target sequence and the sequence of Cin4 we suggest and discuss a model of the
      mechanism of Cin4 integration via in situ cDNA synthesis on an RNA template. The
      longest Cin4 element analysed so far has two non-overlapping open reading frames
      (ORFs) comprising 2793 nucleotides (ORF1) and 3489 nucleotides (ORF2). The
      putative 1163 amino acid long Cin4 protein derived from the sequence of ORF2 has
      the capacity to encode a reverse transcriptase-like protein and a DNA-binding
      domain. The conservation pattern of these two domains and the overall
      organisation of Cin4 is similar to that detected in nonviral retrotransposons in
      animals. The origin and function of Cin4 are discussed.

PMID- 16453816
TI  - Independent and synergistic activity of rol A, B and C loci in stimulating
      abnormal growth in plants.
AB  - The Ri plasmid A4 of Agrobacterium rhizogenes contains within its T-DNA genetic
      information able to trigger root formation in infected plants. Tobacco plants
      regenerated from transformed roots display the hairy root (hr) syndrome. We show
      that DNA fragments containing the rol B locus alone are able to induce root
      formation both in tobacco and kalanchoe tissues. The rol A and the rol C loci by
      themselves are also able to induce root formation in tobacco but not in
      kalanchoe. This capacity to induce root formation in either host is greatly
      increased when the rol A and/or C loci are combined with the rol B locus. Root
      induction is shown to be correlated with the expression of the rol loci.
      Transgenic plants exhibit all the characteristics of the hairy root syndrome only
      when all three loci are present and expressed. Although the activity of the rol
      encoded functions is synergistic, each of them appears to independently influence
      host functions involved in the determination of root differentiation.

PMID- 16453818
TI  - Organization of the murine Ig-related lambda(5) gene transcribed selectively in
      pre-B lymphocytes.
AB  - [This corrects the article on p. 103 in vol. 6, PMID: 3107979.].

PMID- 16453817
TI  - Molecular analysis of the neurogenic locus Enhancer of split of Drosophila
      melanogaster.
AB  - Enhancer of split [E(spl)], one of the neurogenic loci of Drosophila, is located
      in bands 96F8-13. One hundred and fifty kilobases of genomic DNA, spanning the
      E(spl) locus, were cloned by chromosomal walking. DNA heterogeneities associated
      with eleven E(spl) mutations, including three Pr alleles, were mapped to a region
      of 36 kb, and an additional one outside of this region. One of these mutations is
      a deletion of 34 kb that causes severe neural hyperplasia of homozygous embryos
      with complete penetrance. Mutations associated with DNA polymorphisms mapping
      within smaller regions do not lead to a fully penetrant neurogenic phenotype. The
      36-kb region encodes 11 major transcripts, which exhibit distinct temporal and/or
      spatial patterns of expression. The expression of one of these transcripts is
      modified in two different mutants. In addition, one of the mutants [E(spl)] shows
      another transcript, which is not present in the wild-type and co-exists with the
      remaining transcripts. We suggest that more than one of the 11 transcripts are
      necessary for a normal function of the E(spl) locus. The spatial distribution of
      four of these RNAs, which exhibit almost identical patterns of expression,
      strongly suggests that the encoded proteins are required for the process of
      segregation of neural and epidermal lineages.

PMID- 16453819
TI  - Evidence for protection by heat-shock proteins against photoinhibition during
      heat-shock.
AB  - The nuclear-coded 22 kd heat-shock protein (HSP-22) which is transported into the
      chloroplast and localized in the thylakoids was further characterized and found
      to be located in the grana lamellae (stacked thylakoids) as an extrinsic protein
      in the green alga Chlamydomonas reinhardtii. Inhibition of photosynthetic
      electron flow during heat-shock of Chlamydomonas cells was light-dependent,
      occurring at low-light intensities (<100 W/m) as compared with photoinhibition at
      25 degrees C (>1000 W/m). The site of the damage was localized at the photosystem
      II (PS II) reaction center. The damage was drastically increased when heat-shock
      treatment was carried out in the presence of the 80S ribosomal translation
      inhibitor, cycloheximide (CHI). Pre-incubation of Chlamydomonas cells at 42
      degrees C resulted in partial protection against photoinhibition during heat
      shock, as compared with cells pre-incubated at 42 degrees C in the presence of
      CHI which, therefore, did not translate the heat-shock proteins. Analysis of the
      thylakoid polypeptides' pattern by SDS-PAGE revealed that during heat-shock in
      the light, thylakoid proteins became aggregated proportionally to the light
      intensity. Heat-shock in the presence of CHI enhanced the aggregation process
      which, at low light intensities, was specific to the PS II reaction center D1
      protein. The results suggest that the chloroplasts HSPs prevent damage to the PS
      II reaction center during heat-shock in the light.

PMID- 16453820
TI  - Head and tail development of the Drosophila embryo involves spalt, a novel
      homeotic gene.
AB  - Mutations in spalt (sal), a novel homeotic gene on the second chromosome of
      Drosophila, cause opposite transformations in two subterminal regions of the
      embryo: posterior head segments are transformed into anterior thoracic structures
      and anterior tail segments are transformed into posterior abdominal structures.
      The embryonic phenotypes of double mutants for sal and various Antennapedia (ANT
      C) or bithorax (BX-C) genes indicate that sal acts independently of the
      hierarchical order of the latter gene complexes. Trans-regulatory gene mutations
      causing ectopic expression of ANT-C and BX-C genes do not change the realms of
      sal action. It is proposed that the region-specific action of the sal gene
      primarily promotes head as opposed to trunk development, while the BX-C gene AbdB
      distinguishes tail from head.

PMID- 16453821
TI  - Molecular characterization of spalt, a homeotic gene required for head and tail
      development in the Drosophila embryo.
AB  - The isolation, identification and structure of the spalt gene is described. This
      novel homeotic gene of Drosophila is required for the establishment of the
      posterior-most head and the anterior-most tail segments of the embryo. It encodes
      a small mRNA of 0.8 kb which is under the control of over 15 kb of upstream
      sequences as indicated by the phenotype of transformed embryos. The putative
      spalt protein contains internal repeats and other interesting structural motifs
      but no homeo box. The spalt transcript accumulates motifs but no homeo box. The
      spalt transcript accumulates to high levels in the segmental anlagen affected in
      mutant embryos but is also found in regions of the embryo where no functional
      requirement has been demonstrated.

PMID- 16453822
TI  - 7SL RNA from Schizosaccharomyces pombe is encoded by a single copy essential
      gene.
AB  - We have identified an abundant ribonucleoprotein particle from
      Schizosaccharomyces pombe with properties related to those of the vertebrate
      signal recognition particle (SRP), including cytoplasmic localization,
      association with microsomes and ribosomes at low, but not high, salt
      concentrations and high resistance to micrococcal nuclease. The 256-nucleotide
      RNA component carries a 5'-triphosphate group and shows close secondary
      structure, and limited primary sequence homology to vertebrate 7SL RNA. 7SL-like
      RNAs were also detected in a number of other fungi. The single copy gene (SRP7)
      encoding S.pombe 7SL was disrupted by insertion of a transposon carrying the
      selective marker LEU2, and the disrupted gene was used to replace one chromosomal
      SRP7 gene in a diploid strain. Haploid srp7[unk] strains fail to germinate.

PMID- 16453823
TI  - Hybrid DNA tracts may start at different sites during meiotic recombination in
      gene b2 of Ascobolus.
AB  - The initiation of hybrid DNA in the b2 spore colour gene was investigated by the
      analysis of non-Mendelian segregation asci in the progeny of crosses involving
      several allelic b2 mutations. These analyses showed that, instead of the unique
      initiation region of hybrid DNA in b2, assumed previously by Paquette and
      Rossignol (1978), there are multiple sites for hybrid DNA starting. They produce
      major and minor fractions of hybrid DNA. The major fraction starts upstream of
      the left end of the gene, propagates rightwards and can cover its entire length.
      The minor fractions do not span the left b2 end. One of them is detected within
      the left half of the gene, the others within its right half.

PMID- 16453824
TI  - Expression and functional analysis of the Rhizobium meliloti nifA gene.
AB  - The translational initiation point for Rhizobium meliloti nifA, the specific
      activator for nitrogen fixation (nif) genes, was determined. When expressed in an
      Escherichia coli linked transcriptional-translational system the DNA coding for
      the R.meliloti nifA gene produced four polypeptide bands of 71 000, 67 000, 62
      000 and 59 000 daltons. There are three in-frame ATG codons at the N-terminus of
      the gene; by replacing the poor ribosome binding sites of the native DNA with a
      synthetic consensus ribosome binding site prior to each of ATG codons the
      polypeptides were produced at enhanced levels and related to each of the
      initiation codons. The ability of these specifically expressed polypeptides to
      activate nif promoters fused to lacZ was determined. Only the fulllength
      polypeptide activated the Klebsiella pneumoniae nifH, R.meliloti nifH and fixA
      and Bradyrhizobium japonicum nifH and nifD promoters. The R.meliloti fixA
      promoter, contrary to previous evidence, could be activated in E.coli. Deletion
      of the putative N-terminal domain of the R.meliloti nifA gene product greatly
      increased the ability of the protein to activate nif promoters. However,
      deletions retaining part of this domain were not functional. This shows that the
      N-terminal domain is not essential for activity and that its presence decreases
      the full potential function of the protein. Our results are consistent with the
      suggesting that this domain has a regulatory role. In contrast to K.pneumoniae
      nifA protein, the function of the full length and domain deleted forms of
      R.meliloti nifA gene product was sensitive to oxygen in E.coli.

PMID- 16453825
TI  - A DNA sequence element that confers seed-specific enhancement to a constitutive
      promoter.
AB  - Genes encoding beta-conglycinin, a soybean seed storage protein, are expressed
      only in seeds during mid-to-late stages in embryogeny. It was previously
      determined that a DNA sequence 200 nucleotides upstream of the transcriptional
      start site of the gene encoding the alpha'-subunit of beta-conglycinin is
      essential for regulated gene expression in transgenic plants. The regulatory
      effect of this DNA element was tested by inserting the element in different
      positions and different orientations within a chimeric constitutively expressed
      reporter gene. The reporter gene was comprised of the 35S promoter from
      cauliflower mosaic virus (CaMV), a gene encoding chloramphenicol
      acetyltransferase (CAT) and the polyadenylation signal from the alpha'-subunit
      gene. The element had no significant effect on the expression of the CAT gene in
      roots, stems, or leaves, regardless of the position of its insertion (i.e. 5 or 3
      of the gene). However, there was 25- to 40-fold enhancement of CAT gene
      expression in seeds during mid-to-late stages of embryo development when the
      element was placed in either orientation within the 35S promoter. There was 2- to
      4-fold enhancement of CAT activity when the element was placed 3' of the CAT
      coding sequence. No enhancement was detected when the element was placed
      downstream of the 3' non-coding region. This is, to our knowledge, the first
      identification of a cis-acting element that enhances gene expression in a tissue
      specific and temporally regulated manner during embryo development in plants.

PMID- 16453826
TI  - Replication termini in the rDNA of synchronized pea root cells (Pisum sativum).
AB  - In synchronized root cells of Pisum sativum (cv. Alaska) the joining of nascent
      replicons is delayed until cells reach the S-G(2) boundary or early G(2) phase.
      To determine if the delayed ligation of nascent chains occurs at specific
      termination sites, we mapped the location of arrested forks in the ribosomal DNA
      (rDNA) repeats from cells in late S and G(2) phases. Two-dimensional (neutral
      alkaline) agarose electrophoresis and Southern blot hybridization with specific
      rDNA sequences show that only cells located at the S-G(2) boundary and early G(2)
      phase produce alkali-released rDNA fragments of discrete size. The released
      fragments are from a particular restriction fragment, demonstrating that the
      replication forks stop non-randomly within the rDNA repeats. Indirect end
      labeling with probes homologous to one or the other end of the fork-containing
      restriction fragment shows that there are two termination regions, T(1) and T(2),
      where forks stop. T(1) is located in the non-transcribed spacer and T(2) is at
      the junction between the non-transcribed spacer and the 18S gene. The two termini
      are separated by 1.3 kb. Replication forks stop at identical sites in both the
      8.6- and 9.0-kb rDNA repeat size classes indicating that these sites are sequence
      determined.

PMID- 16453828
TI  - Nuclear mutations specifically affect the synthesis and/or degradation of the
      chloroplast-encoded D2 polypeptide of photosystem II in Chlamydomonas
      reinhardtii.
AB  - To study the interaction of the nuclear and chloroplast genomes in the biogenesis
      of the photosynthetic apparatus, nuclear mutants of Chlamydomonas reinhardtii
      deficient in photosystem II (PSII) activity were analyzed. Two independently
      isolated, allelic nuclear mutants show a pleiotropic reduction in a set of
      functionally related PSII polypeptides. Immunoblot analysis reveals that the two
      mutants, nac-1-18 and nac-1-11, accumulate reduced amounts of the chloroplast
      encoded polypeptides P5 and P6 and are completely deficient in polypeptides D1
      and D2. Polypeptides of the oxygen-evolving and light-harvesting complexes
      associated with PSII, however, are present at wild-type levels. Analysis of mRNAs
      encoding PSII polypeptides from these mutants indicates that all messages are
      present, although some species, including the D2 message, are significantly
      elevated. When mutant cells are pulse-labeled for 10 min with [C]acetate, a
      greatly reduced amount of labeled D2 protein is observed, while all other PSII
      polypeptides are synthesized normally. These data indicate that the mutations
      present in nac-1-18 and nac-1-11 affect a nuclear gene whose product specifically
      controls the translation and/or degradation of the chloroplast-encoded D2
      polypeptide.

PMID- 16453827
TI  - In vitro expression of cauliflower mosaic virus genes.
AB  - The eight major open reading frames (ORFs) of cauliflower mosaic virus (CaMV)
      have been cloned for in vitro transcription and translation. All the ORFs could
      be translated. Using antisera against either purified virus or specific gene
      products, the translation products were screened by immunoprecipitation. The
      products of ORFs III, IV and V were confirmed as components of the virions.
      Molecular weights of primary translation products were determined and compared
      with those found in vivo. A further series of constructs was designed to test
      whether translation of adjacent ORFs is coupled in a relay-race fashion as
      proposed on the basis of earlier in vivo mutagenesis studies. Downstream genes on
      dicistronic RNAs could be translated, although inefficiently. In view of the
      similarity between the arrangement of the CaMV coat protein and reverse
      transcriptase genes and the corresponding genes of retroviruses, we asked whether
      the CaMV reverse transcriptase could be expressed in vitro as a fusion protein,
      e.g. by ribosomal frame shifting. No such fusion was observed, suggesting that
      the polymerase gene is translated from its own ATG.

PMID- 16453829
TI  - Transmembrane orientation and receptor-like structure of the Rhizobium meliloti
      common nodulation protein NodC.
AB  - The 46.8-kd NodC protein of Rhizobium meliloti is a membrane protein, essential
      for nodule formation. Gene fusions of nodC to a portion of the lambda cI
      repressor gene were used to define the membrane-anchor domain which is necessary
      for membrane insertion of the NodC protein into the membrane. The transmembrane
      orientation of NodC was confirmed by surface-specific radiolabeling and
      proteolysis experiments. A highly hydrophobic transmembrane-anchor domain was
      found near the carboxyl terminus, separating a large extracellular domain which
      contains an unusual cysteine-rich cluster from a short putative intracellular
      domain. Cross-linking studies showed that the NodC protein exists in the membrane
      probably as a dimer. The domain structure of the NodC protein shows striking
      similiarities with cell surface receptors. In nodules of various legumes a
      truncated form of the NodC protein was detected. The processed NodC was
      associated with the bacteroids and the amount of this protein increased during
      nodule development.

PMID- 16453830
TI  - The photosynthetic water oxidase: its proton pumping activity is short-circuited
      within the protein by DCCD.
AB  - The photosynthetic water oxidase is composed of 15 polypeptides which are grouped
      around two functional parts: photosystem II and the catalytic manganese centre.
      Photochemically driven vectorial electron transfer between the manganese centre
      and bound plastoquinone causes deprotonation-protonation reactions at opposite
      sides of the thylakoid membrane. Thereby the water oxidase acts as a proton pump.
      Incubation of stacked thylakoids with N,N'-dicyclohexylcarbodiimide (DCCD) short
      circuited its proton pumping activity. Under flashing light, the extent of both
      proton release into the lumen by water oxidation and of proton uptake from the
      medium by reduced quinone was diminished. Instead there was a rapid electrogenic
      backreaction with a strong H/D-isotope effect. Apparently protons which were
      produced by water oxidation were channelled across the transmembrane protein to
      the bound quinone. A more rapid protonation of the reduced quinone was evident
      from a shortening of the time lag for the reduction of photosystem I. These
      effects were paralleled by the preferential labelling with [C]DCCD in stacked
      thylakoids of two polypeptides with 20 and 24 kd apparent molecular mass. These
      may be capping the oxidizing and the reducing terminus of the water oxidase to
      control proton extrusion and proton uptake respectively.

PMID- 16453832
TI  - Developmental analysis of a hybrid gene composed of parts of the Ubx and abd-A
      genes of Drosophila.
AB  - C1 is a mutation in the bithorax complex (BX-C) of Drosophila resulting from the
      deletion of parts of the Ubx and abd-A genes. We show that the ;hybrid' gene
      formed by the fusion of the remaining parts of Ubx and abd-A (5'abd-A/Ubx3') is
      functional and developmentally active. It specifies parasegment patterns with a
      mixture of thoracic and abdominal identities. The hybrid gene also has other
      properties typical of conventional bithorax genes: it can be spatially
      derepressed in the absence of trans-acting genes like extra Sex combs or Polycomb
      and in turn represses other homeotics like Sex combs reduced. The comparison of
      embryos containing exclusively hybrid gene activity with others having no BX-C
      function indicates that the hybrid gene is active in the body region defined by
      PS5 to PS14. The expression in PS5 and PS6 suggests that one control region (abx)
      of Ubx can regulate the transcription of the abd-A promoter.

PMID- 16453831
TI  - Structure of U2 snRNA genes of Arabidopsis thaliana and their expression in
      electroporated plant protoplasts.
AB  - We have characterized the U2 snRNA gene family in the higher plant Arabidopsis
      thaliana. It consists of 10-15 genes which do not appear to be closely clustered.
      Six of the U2 genes were sequenced and the structure of the Arabidopsis U2 RNA
      termini was determined in order to define the coding regions. Each of the genes
      codes for a distinct RNA differing from the others by 2-13 point mutations,
      localized in the 3' part of the 196 nt-long RNA. The upstream non-coding regions
      of all genes show strong sequence similarity in positions -81 to -1 and contain
      three highly conserved sequence elements: GTCCCACATCG (positions -78 to -68; 100%
      conservation), GTAGTATAAATA (-37 to -26) and CAANTC (-6 to -1). The coding
      regions are followed by the sequence CAN(7-9)AGTNNAA, a putative termination
      signal. The expression of three of the genes was studied in electroporated
      Orychophragmus violaceus and Nicotiana tabacum protoplasts. The genes, one of
      which contains a T --> C change in the Sm antigen binding site, were actively
      transcribed and processed into U2 RNAs of the expected size and containing
      trimethylguanosine caps. Deletion analysis indicates that sequences upstream of
      the conserved -80 to -1 region are not important for transcription in
      protoplasts. The 5'-terminal parts of U2 RNAs from several monocot and dicot
      plants were sequenced. This region, containing the sequence implicated in base
      pairing with the branch point in pre-mRNA introns, is identical in all U2 RNAs
      examined.

PMID- 16453833
TI  - The structure and expression of a hybrid homeotic gene.
AB  - We describe the structure and expression of an exceptional bithorax complex
      mutation, C1. This deletion mutation removes major portions of both the
      Ultrabithorax (Ubx) and abdominal-A (abd-A) protein coding regions, yet retains
      many of the functions normally executed by these genes. We show that the ends of
      the C1 deletion map to analogous positions within the Ubx and abd-A transcription
      units, and that the deletion chromosome gives rise to a set of novel fusion
      transcripts that may encode hybrid abd-A/Ubx proteins. These fusion products are
      transcribed from the abd-A promoter, but exhibit a novel spatial pattern of
      expression that combines aspects of the normal Ubx and abd-A distributions. This
      pattern provides evidence for the existence of regulatory elements located in the
      3' region of the Ubx transcription unit that can act on the abd-A promoter at a
      distance of at least 20 kb.

PMID- 16453834
TI  - Differential light regulated expression of nuclear genes encoding chloroplast and
      cytosolic glyceraldehyde-3-phosphate dehydrogenase in Nicotiana tabacum.
AB  - When tobacco (Nicotiana tabacum) plants were transferred from the dark to
      continuous white light, the steady-state mRNA levels transcribed from the nuclear
      genes encoding chloroplast (GapA and GapB) glyceraldehyde-3-phosphate
      dehydrogenase increased at least 30- to 50-fold, while the mRNA level for the
      cytosolic enzyme (GapC) increased only 10-fold. Kinetic analyses show that the
      rates of mRNA accumulation for GapA and GapB are identical reaching steady-state
      levels after 24-48 h in light. In contrast, mRNA accumulation for the GapC gene
      shows a completely different kinetic pattern, accumulating much faster than that
      of GapA and GapB. These results suggest that expression of GapC and GapA/B genes
      are controlled by different light regulated mechanisms and nuclear run-on
      analyses suggest that these effects are primarily due to increased transcription.

PMID- 16453835
TI  - Genetic analysis of tomato golden mosaic virus: the coat protein is not required
      for systemic spread or symptom development.
AB  - The geminiviruses are a unique group of higher plant viruses that are composed of
      twin isometric particles which contain circular, single-stranded DNA. Tomato
      golden mosaic virus (TGMV), a whitefly-transmitted agent, belongs to the subgroup
      of geminiviruses whose members possess a bipartite genome. The TGMV A genome
      component has the capacity to encode at least four proteins. One of these is the
      viral coat protein, as inferred by homology with coat-protein, genes of other
      geminiviruses and by the observation of typical geminate particles in transgenic
      plants that contain inserts of TGMV A DNA. We have investigated the role of the
      coat protein in TGMV replication and report here that its coding sequence may be
      interrupted or substantially deleted without loss of infectivity. However,
      certain coat-protein mutants showed reproducible delays in time of symptom
      appearance as well as reduced symptom development, when inoculated onto
      transgenic Nicotiana benthamiana plants containing the TGMV B component. The most
      attenuated symptoms were seen with a mutant in which the coat-protein coding
      sequence was almost entirely deleted. The significance of these findings for the
      development of plant vectors from TGMV DNA is discussed.

PMID- 16453836
TI  - NEW PRODUCT NEWS FROM HOEFER: New 24 Place Slot Blotting Manifold Allows
      Individual Collection Of Filtrate.

PMID- 16453837
TI  - The molecular basis of sulfonylurea herbicide resistance in tobacco.
AB  - The enzyme acetolactate synthase (ALS) is the target enzyme for the sulfonylurea
      and imidazolinone herbicides. We describe the isolation and characterization of
      the ALS genes from two herbicide-resistant mutants, C3 and S4-Hra, of Nicotiana
      tabacum. There are two distinct ALS genes in tobacco which are 0.7% divergent at
      the amino acid sequence level. The C3 mutant has a single Pro-Gln replacement at
      amino acid 196 in one ALS gene. This gene is termed the class I gene and is
      equivalent to the SuRA locus. The S4-Hra mutant has two amino acid changes in the
      other ALS gene. This gene is termed the class II gene or the SuRB locus. The S4
      Hra mutant includes a Pro-Ala substitution at amino acid 196 and a Trp-Leu
      substitution at amino acid 573. Gene reintroduction experiments have confirmed
      that these amino acid substitutions are responsible for the herbicide resistance
      phenotypes. Transgenic plants carrying these genes are highly resistant to
      sulfonylurea herbicide applications.

PMID- 16453838
TI  - Endosperm-specific activity of a zein gene promoter in transgenic tobacco plants.
AB  - Transgenic tobacco plants containing maize gene (Z4) encoding a 23-kd zein
      protein, which is normally synthesized in the endosperm of maize seeds, were
      obtained using a modified Ti plasmid vector. Although a polyadenylated transcript
      homologous to the Z4 gene was present in the seeds of some of these transgenic
      plants, zein protein could not be detected in any of the plants tested (35
      total). To simplify the analysis of the tissue specificity of the Z4 promoter
      (Z4(pro)) in different organs of transformed tobacco plants, additional
      transgenic plants containing the chimeric genes Z4(pro)-CAT and Z4(pro)-GUS were
      produced. Very weak seed-specific CAT activity was observed in one out of ten
      Z4(pro)-CAT-transformed plants. When the more sensitive GUS assay system was used
      to evaluate Z4(pro) activity in tobacco, it could be shown in all 11 transgenic
      plants obtained that GUS activity was restricted to the endosperm tissue of
      transgenic tobacco seeds. To study the synthesis and stability of the zein
      proteins in different organs of transgenic tobacco plants, the Z4 protein-coding
      region and also a cDNA clone (A30) encoding a 19-kd zein protein were placed
      under the control of the 35S promoter (35S(pro)) of cauliflower mosaic virus.
      Undegraded zein proteins of both size classes were detected in roots, leaves and
      endosperm tissue, but not embryos, of mature seeds from 35S(pro)-zein-transformed
      plants. The zein proteins did not appear to be broken down during tobacco seed
      germination; synthesis of zeins began in green cotyledons.

PMID- 16453839
TI  - Interaction of a nodule specific, trans-acting factor with distinct DNA elements
      in the soybean leghaemoglobin Ibc(3) 5' upstream region.
AB  - Nuclear extracts from soybean nodules, leaves and roots were used to investigate
      protein-DNA interactions in the 5' upstream (promoter) region of the soybean
      leghaemoglobin lbc(3) gene. Two distinct regions were identified which strongly
      bind a nodule specific factor. A Bal31 deletion analysis delimited the DNA
      elements responsible for the binding of this factor, which map at nucleotides 
      223 to -246 (element 1) and -161 to -176 (element 2), relative to the start point
      of transcription. Competition experiments strongly suggest that both elements
      bind to the same nodule specific factor, but with different affinities. Elements
      1 and 2 share a common motif, although their AT-rich DNA sequences differ.
      Element 2 is highly conserved at an analogous position in other soybean lb gene
      5' upstream regions.

PMID- 16453841
TI  - Import of a precursor protein into chloroplasts is inhibited by the herbicide
      glyphosate.
AB  - Import of the precursor to 5-enolpyruvylshikimate-3-phosphate synthase (pEPSPS)
      into chloroplasts is inhibited by the herbicide glyphosate. Inhibition of import
      is maximal at glyphosate concentrations of >/=10 mum and occurs only when pEPSPS
      is present as a ternary complex of enzyme-shikimate-3-phosphate-glyphosate.
      Glyphosate alone had no effect on the import of pEPSPS since it is not known to
      interact with the enzyme in the absence of shikimate-3-phosphate. Experiments
      with wild-type and glyphosate-resistant mutant forms of pEPSPS show that
      inhibition of import is directly proportional to the binding constants for
      glyphosate. Inhibition of import is thus a direct consequence of glyphosate
      binding to the enzyme-shikimate-3-phosphate complex. The potential for non
      specific effects of glyphosate on the chloroplast transport mechanism has been
      discounted by showing that import of another chloroplast-designated protein was
      unaffected by high concentrations of glyphosate and shikimate-3-phosphate. The
      mechanism of import inhibition by glyphosate is consistent with a precursor
      unfolding/refolding model.

PMID- 16453840
TI  - Analysis of the mechanism of protection in transgenic plants expressing the
      potato virus X coat protein or its antisense RNA.
AB  - Transgenic tobacco plants engineered to express either the potato virus X (PVX)
      coat protein (CP+) or the antisense coat protein transcript (CP-antisense) were
      protected from infection by PVX, as indicated by reduced lesion numbers on
      inoculated leaves, delay or absence of systemic symptom development and reduction
      in virus accumulation in both inoculated and systemic leaves. The extent of
      protection observed in CP+ plants primarily depended upon the level of expression
      of the coat protein. Plants expressing antisense RNA were protected only at low
      inoculum concentrations. The extent of this protection was even lower than that
      observed in plants expressing low levels of CP. In contrast to previous reports
      for plants expressing tobacco mosaic virus or alfalfa mosaic virus CP,
      inoculation of plants expressing high levels of PVX CP with PVX RNA did not
      overcome the protection. Specifically, lesion numbers on inoculated leaves and
      PVX levels on inoculated and systemtic leaves of the CP+ plants were reduced to a
      similar extent in both virus and RNA inoculated plants. Although these results do
      not rule out that CP-mediated protection involves inhibition of uncoating of the
      challenge virus, they suggest that PVX CP (or its RNA) can moderate early events
      in RNA infection by a different mechanism.

PMID- 16453842
TI  - Imported large subunits of ribulose bisphosphate carboxylase/oxygenase, but not
      imported beta-ATP synthase subunits, are assembled into holoenzyme in isolated
      chloroplasts.
AB  - The large subunit of ribulose bisphosphate carboxylase from Anacystis nidulans
      6301, and the beta subunit of chloroplast ATP synthase from maize, were fused to
      the transit peptide of the small subunit of ribulose bisphosphate carboxylase
      from soybean. These proteins were assayed for post-translational import into
      isolated pea chloroplasts. Both proteins were imported into chloroplasts.
      Imported large subunits were associated with two distinct macromolecular
      structures. The smaller of these structures was a hybrid ribulose bisphosphate
      carboxylase holoenzyme, and the larger was the binding protein oligomer. Time
      course experiments following import of the large subunit revealed that the amount
      of large subunit associated with the binding protein oligomer decreased over
      time, and that the amount of large subunit present in the assembled holoenzyme
      increased. We also observed that imported small subunits of ribulose bisphosphate
      carboxylase, although predominantly present in the holoenzyme, were also found
      associated with the binding protein oligomer. In contrast, the imported beta
      subunit of chloroplast ATP synthase did not assemble into a thylakoid-bound
      coupling factor complex.

PMID- 16453844
TI  - EMBO members in North America.

PMID- 16453843
TI  - Three-dimensional structure of the regular surface glycoprotein layer of
      Halobacterium volcanii from the Dead Sea.
AB  - A three-dimensional reconstruction from electron micrographs of negatively
      stained cell envelopes of Halobacterium volcanii has revealed the structure of
      the surface glycoprotein to a resolution of 2 nm. The glycoprotein is arranged on
      a p6 lattice with a lattice constant of 16.8 nm. It forms 4.5 nm high, dome
      shaped, morphological complexes with a narrow pore at the apex opening into a
      ;funnel' towards the cell membrane. The polarity of the structure was derived
      from freeze-etching experiments and ;edge' views. Six radial protrusions emanate
      from each morphological complex and join around the 3-fold axis to provide
      lateral connectivity. Using the primary structure of the surface glycoprotein of
      the closely related species Halobacterium halobium (Lechner and Sumper, 1987) and
      the cell envelope profile from a previous X-ray analysis of the same species
      (Blaurock et al., 1976) we have integrated our reconstruction into a model of
      halobacterial cell envelope.

PMID- 16453845
TI  - New EMBO members elected in the 1988 ballot.

PMID- 16453846
TI  - Erratum: Major surface antigen p190 of Plasmodium falciparum: detection of common
      epitopes present in a variety of plasmodia isolates.
AB  - [This corrects the article on p. 225 in vol. 7, PMID: 2452082.].

PMID- 16453847
TI  - Leaf-specific thionins of barley-a novel class of cell wall proteins toxic to
      plant-pathogenic fungi and possibly involved in the defence mechanism of plants.
AB  - A novel class of highly abundant polypeptides with antifungal activity has been
      detected in cell walls of barley leaves. Similar polypeptides known as thionins
      occur not only in monocotyledonous but also in various dictoyledonous plants. The
      leaf-specific thionins of barley are encoded by a complex multigene family, which
      consists of at least 50-100 members per haploid genome. All of these genes are
      confined to chromosome 6. The toxicity of these thionins for plant pathogenic
      fungi and the fact that their synthesis can also be triggered by pathogens
      strongly suggest that thionins are a naturally occurring, inducible plant protein
      possibly involved in the mechanism of plant defence against microbial infections.

PMID- 16453848
TI  - Novel mechanisms for maturation of chloroplast transfer RNA precursors.
AB  - Despite the prokaryotic origins of chloroplasts, a plant chloroplast tRNA
      precursor is processed in a homologous in vitro system by a pathway distinct from
      that observed in Escherichia coli, but identical to that utilized for maturation
      of nuclear pre-tRNAs. The mature tRNA 5' terminus is generated by the site
      specific endonucleolytic cleavage of an RNase P (or P-type) activity. The 3' end
      is likewise produced by a single precise endonucleolytic cut at the 3' terminus
      of the encoded tRNA domain. This is the first complete structural
      characterization of an organellar tRNA processing system using a homologous
      substrate. In contrast to eubacterial RNase P, chloroplast RNase P does not
      appear to contain an RNA subunit. The chloroplast activity bands with bulk
      protein at 1.28 g/ml in CsCI density gradients, whereas E.coli RNase P bands as
      ribonucleoprotein at 1.73 g/ml. Chloroplast RNase P activity survives treatment
      with micrococcal nuclease (MN) at levels 10- to 100-fold higher than those
      required to totally inactivate the E.coli enzyme. The chloroplast system is
      sensitive to a suppression of tRNA processing, caused by binding of inactive MN
      to pre-tRNA substrate, which is readily overcome by addition of carrier RNA to
      the assay.

PMID- 16453849
TI  - Two concomitant base substitutions in the putative replicase genes of tobacco
      mosaic virus confer the ability to overcome the effects of a tomato resistance
      gene, Tm-1.
AB  - A resistance-breaking strain of tobacco mosaic virus (TMV), Ltal, is able to
      multiply in tomatoes with the Tm-1 gene, unlike its parent strain, L. Comparison
      of the genomic sequences of L and Lta1 revealed two base substitutions resulting
      in amino acid changes in the 130 and 180 kd proteins: Gln-979 --> Glu and His-984
      --> Tyr. To clarify their involvement in the resistance-breaking property of
      Lta1, the two substitions were introduced into L by an in vitro transcription
      system to generate a mutant strain, T1. T1 multiplied in Tm-1/Tm-1 tomatoes with
      symptoms as did Lta1. Two additional mutant strains were constructed, each of
      which had one base substitution which caused a His-984 --> Tyr change (T2) or a
      Gln-979 --> Glu change (T3). T3 multiplied in tomato plants and protoplasts with
      the Tm-1 gene, indicating that the single base substitution is sufficient to
      overcome the resistance. T2 also multiplied, but its multiplication was greatly
      decreased. Although no sequence changes were detected in any progeny viruses
      recovered from plants without the Tm-1 gene, progeny viruses recovered from T2-
      or T3- inoculated Tm-1/Tm-1 tomatoes contained in most cases viruses with
      additional second base substitutions. They caused amino acid changes near the
      mutagenized residues, suggesting that the ability of T3 to overcome the
      resistance is not the same as that of Lta1. Sequencing of the genomic RNAs of
      other independently isolated resistance-breaking strains revealed the same two
      base substitutions found in the Lta1 RNA. These observations suggest that the two
      concomitant base substitutions, and possibly also the resulting amino acid
      changes, guarantee successful replication of these TMV strains in tomatoes
      containing the Tm-1 gene. A strong correlation was found between the ability to
      overcome the resistance and a decrease in local net charge, suggesting the
      involvement of an electrostatic interaction between the viral 130 and 180 kd
      proteins and a putative host resistance factor.

PMID- 16453850
TI  - Expression of a bacterial gene in plants mediated by infectious geminivirus DNA.
AB  - A viable coat protein deletion mutant of cassava latent virus (CLV) DNA 1 has
      been isolated, suggesting that this geminivirus might be exploited as a gene
      replacement vector. An extensive deletion of 727 nucleotides within the coat
      protein gene renders DNA 1 non-infectious. Chimeric clones have been constructed
      in which the deleted coat protein open reading frame has been replaced by the
      coding region of the bacterial chloramphenicol acetyl transferase (CAT) gene.
      Infectivity is restored to DNA 1 when the CAT gene is inserted in either
      orientation, producing symptoms typical of CLV infection. The results demonstrate
      that the coat protein plays no essential role in virus spread throughout the
      host. Levels of CAT expression of 80 U/mg soluble protein occur in systemically
      infected Nicotiana benthamiana leaves when the CAT gene is fused in-frame to the
      amino terminus of the coat protein, providing a sensitive assay for viral DNA
      replication.

PMID- 16453852
TI  - Corrigendum: Primary structure of the human, membrane-associated Ca-binding
      protein p68: a novel member of a protein family.
AB  - [This corrects the article on p. 21 in vol. 7, PMID: 3258820.].

PMID- 16453853
TI  - Erratum: Latent membrane perturbation activity of a mitochondrial precursor
      protein is exposed by unfolding.
AB  - [This corrects the article on p. 1153 in vol. 7, PMID: 2841114.].

PMID- 16453851
TI  - The intergenic region of maize streak virus contains promoter elements involved
      in rightward transcription of the viral genome.
AB  - Maize streak virus (MSV), a geminivirus with a one-component genome, encodes a
      major coat protein RNA which accumulates in infected plants. Using a maize
      protoplast cell transient expression system, we have defined and studied the
      promoter which drives rightward transcription of the RNA encoding the coat
      protein. We have identified a 122 bp upstream segment that enhances promoter
      activity and functions as an upstream activating sequence (UAS). The UAS lies in
      the starting intergenic region of the viral genome and includes a region which is
      similar in all geminiviruses. The 122 bp UAS activates the MSV core promoter in
      an orientation, but not position, independent fashion. The MSV promoter UAS is
      interchangeable with a similar element in the cauliflower mosaic virus (CaMV) 35S
      RNA core promoter, that is the MSV UAS will activate the CaMV 35S core promoter
      and vice versa. However, the MSV promoter UAS specifically binds proteins in
      maize nuclear extracts which appear to differ from those bound by the
      functionally equivalent region of the CaMV 35S promoter.

PMID- 16453855
TI  - Investigation of the structure of trimeric and monomeric photosystem I reaction
      centre complexes.
AB  - Electron microscopy of monomeric and trimeric forms of the reaction centre of
      photosystem I from the thermophilic cyanobacterium Phormidium laminosum has
      allowed the construction of a three-dimensional model describing the shape of the
      complex. The trimeric form of the Photosystem I reaction centre complex was found
      to have a very regular shape corresponding to a rounded equilateral triangle with
      edges 18 nm long and a thickness of 6 nm. A distinctive chiral arrangement of the
      three reaction centres in the trimer could be observed on one face of the
      complex, whereas the opposing face appeared to be smooth with no distinctive
      internal features. The monomeric reaction centre is roughly pearshaped, with a
      length of 15 nm and a width of 9 nm. A thickness of 6 nm is assumed from
      comparison with the trimer. It is predicted to lie with its shortest axis
      spanning the membrane. A double-lobed structure, with one lobe larger than the
      other, was occasionally observed for the monomeric reaction centre. No
      experimental evidence could be obtained for the existence of the trimeric form in
      the membrane. The formation of the trimeric form after detergent extraction is
      suggested. The trimeric form was found to be more stable than the monomeric form
      in solutions containing anionic and non-ionic detergents.

PMID- 16453854
TI  - The Abdominal-B gene of Drosophila melanogaster: overlapping transcripts exhibit
      two different spatial distributions.
AB  - The Abdominal-B (Abd-B) gene of Drosophila controls the specification of segment
      identities in the posterior abdomen. We describe here the spatial and temporal
      distribution of Abd-B transcripts. At least five RNA species are detected on
      Northern blots with probes within the region of the Abd-B homeobox. We have
      identified probes specific for subsets of these transcripts and have used these
      probes to study the distribution of each subset by in situ hybridization to
      embryonic tissue sections. The transcripts can be divided into two groups: one
      group is expressed maximally in parasegment (PS)13 and extends anteriorly to
      PS10; the other is expressed only in PS14 and 15. These two different patterns of
      expression correspond to the anatomical domains defined by two classes of
      mutations in Abd-B. These results help explain the complex genetic interactions
      and phenotypes of mutations within this gene.

PMID- 16453857
TI  - Erratum: Protein/DNA architecture of the DNase I hypersensitive region of the
      Drosophila hsp26 promoter.
AB  - [This corrects the article on p. 2191 in vol. 7, PMID: 2901349.].

PMID- 16453856
TI  - Unmethylated CpG islands associated with genes in higher plant DNA.
AB  - The genomes of many higher plant species are the most highly methylated among
      eukaryotes. We report here that in spite of their heavy methylation, genomic DNAs
      from four plant species contain a fraction that is very rich in non-methylated
      sites. The fraction was characterized in maize where it represents about 2.5% of
      the total nuclear genome. In order to establish the genomic origin of the
      fraction, three maize genes containing clustered CpG were tested for methylation
      and were found to be non-methylated in the CpG-rich regions. By contrast, tested
      CpGs were methylated in a gene whose sequence showed no clustering of CpG. These
      observations suggest that the CpG-rich fraction of plants is at least partially
      derived from non-methylated regions that are associated with genes. A similar
      phenomenon has been described in vertebrate genomes. We discuss the evolution of
      CpG islands in both groups of organisms, and their possible uses in mapping and
      gene isolation in plants.

PMID- 16453858
TI  - Constitutive transcription and regulation of gene expression in non
      photosynthetic plastids of higher plants.
AB  - The plastid genome in higher plants contains >50 genes for rRNAs, tRNAs and
      proteins for transcriptional and translational functions, besides the genes
      encoding photosynthetic proteins. Considering the totipotency of most higher
      plant cells and the differentiation capacity of plastids, it can be inferred that
      at least the genes for genetic functions must be constitutively expressed in all
      plant organs, including non-photosynthetic roots, to maintain a basal level of
      transcriptional and translational activities. To test this hypothesis,
      transcription, RNA accumulation and polysome formation were analyzed in root
      amyloplasts, and in plastids from hypocotyls and cotyledons of dark-grown spinach
      seedlings. The results for 10 representative genes show that they are
      constitutively transcribed at relative rates which are similar in root
      amyloplasts and leaf chloroplasts. The differential accumulation of their mRNAs
      in roots and other non-photosynthetic plant organs is controlled at the post
      transcriptional level by a developmental program. Although mRNAs for
      photosynthetic proteins are detectable in root amyloplasts, some of them are
      specifically depleted from polysomes relative to mRNAs for ribosomal proteins.
      This translational discrimination does not result from modifications in splicing
      or 5'- and 3' -end processing of mRNAs for photosynthetic proteins, since
      processing is identical in root amyloplasts and leaf chloroplasts. The results
      support the model of constitutive transcription of the plastid genome, and
      indicate that the expression of most plastid genes in spinach plants is
      controlled primarily by post-transcriptional and translational mechanisms.

PMID- 16453859
TI  - NEW PRODUCT NEWS FROM HOEFER: New 24 Place Slot Blotting Manifold Allows
      Individual Collection Of Filtrate.

PMID- 16453860
TI  - Characterization of the maize transposable element Ac by internal deletions.
AB  - We have used the ability of Ac to transpose in tobacco to determine which Ac
      sequences are required for transposition, using a phenotypic assay for Ac
      excision from an NPTII gene in which excisions of Ac result in calli resistant to
      the antibiotic kanamycin (Baker et al., 1987). Here we show that deletion of the
      Ac DNA which encodes the untranslated leader of the Ac transcript does not
      prevent Ac excision. A deletion which removes 110 bp including the first 75 bp of
      long open reading frame prevents Ac excision in tobacco cells. However, it will
      excise in tobacco cells previously transformed with Ac indicating that deletion
      of the region prevents the synthesis of a product required for Ac excision.
      Deletion of the Ac sequences between bp 44 and bp 92 or from bp 75 to bp 181
      abolishes, or strongly reduces, transposition in cells which are already
      transgenic for an active Ac element. This indicates that these deleted elements
      have lost sequences which are required for the transposon to respond to the
      transposase, when the enzyme is produced in trans. We also describe a tobacco
      strain transformed with a Ds element stably inserted wtihin an NPTII gene. This
      strain is Km and was retransformed with a construct containing the open reading
      frame (ORF) of the 3.5-kb Ac transcript expressed from a plant promoter.
      Expression of the cDNA construct promotes excision of the Ds element. These data
      suggest that the 3.5-kb transcript of Ac encodes the only Ac product required for
      transposition, i.e. the transposase function.

PMID- 16453862
TI  - Notes added in proof.

PMID- 16453861
TI  - Characterization of an anion-permeable channel from sugar beet vacuoles: effect
      of inhibitors.
AB  - The vacuole occupies 25-95% of the plant cell volume and plays an essential role
      in maintaining cytoplasmic homeostasis of nutrients and ions. Recent patch-clamp
      studies identified ion channels and electrogenic pumps as pathways for the
      movement of ions and metabolites across the vacuolar membrane (tonoplast). At
      high cytoplasmic Ca (>10 M) and negative potentials (inside the vacuole) non
      selective channels of the ;slow-vacuolar (SV)-type' were activated resulting in
      anion release or cation influx. In the present study these vacuolar channels were
      characterized pharmacologically by ion channel inhibitors. The cation-transport
      inhibitors Ba, TEA and amiloride caused only partial and reversible block of the
      ;SV-type'channels, whereas anion-transport inhibitors strongly affected the
      vacuolar channels. Pyridoxalphosphate and the dimethylaminecarboxylate derivates
      anthracene-9-carboxylic acid and C 144 reversibly blocked the channels up to 70%
      and Zncl(2) up to 95%. DIDS and SITS inhibited this channel irreversibly up to
      95%. The block developed under a variety of experimental conditions using
      solutions containing combinations of permanent cations and anions. The DIDS
      binding site is located on the cytoplasmic surface of the tonoplast, as
      intravacuolar DIDS did not block the channels. DIDS concentrations in the
      micromolar range, efficient in blocking 70-80% of the ;SV-type' channels did not
      significantly affect ATP-induced or pyrophosphate-induced proton-pumps. Stilbene
      derivatives may therefore be useful tools for studies on the substrate binding
      site on this vacuolar channel and for channel isolation.

PMID- 16453863
TI  - Corrigendum: Heat shock but not other stress inducers leads to the disruption of
      a subset of snRNPs and inhibition of in vitro splicing in HeLa cells.
AB  - [This corrects the article on p. 3509 in vol. 7, PMID: 2974799.].

PMID- 16453864
TI  - Gene targeting in plants.
AB  - Although the generation of transgenic plants is now routine, the integration of
      foreign genetic information has so far been at random sites in the genome. We now
      present evidence for directed integration into a predicted location in the host
      plant genome. Protoplasts of transgenic tobacco (Nicotiana tabaccum) plants
      carrying copies of a partial, non-functional drug-resistance gene in the nuclear
      DNA were used as recipients for DNA molecules containing the missing part of the
      gene. Molecular and genetic data confirm the integration of the foreign DNA
      through homologous recombination within overlapping parts of the protein coding
      region, resulting in the formation of an active gene in the host chromosome. This
      approach is referred to as gene targeting. The gene targeting frequency (the
      number of drug-resistant clones resulting from gene correction compared to the
      number of resistant clones from parallel experiments with a similar non
      interrupted hybrid gene) was 0.5-4.2x10. These experiments demonstrate the
      possibility of producing transgenic plants with desired modifications to a
      specific nuclear gene.

PMID- 16453865
TI  - UV-inducible transient expression in parsley protoplasts identifies regulatory
      cis-elements of a chimeric Antirrhinum majus chalcone synthase gene.
AB  - It was shown previously that parsley protoplasts retain differential
      responsiveness to external stimuli, e.g. UV light. This opened the way for the
      development of transient expression assays to identify DNA sequences acting as
      regulatory cis-elements in the transcriptional activation of UV-inducible plant
      genes. The chalcone synthase (chs) gene of Antirrhinum majus (Snapdragon) is
      inducible by visible and by UV light. We demonstrate that the kinetics of light
      induction of a chimeric A.majus chs-nptII gene observed during transient
      expression in the parsley protoplasts reflect the kinetics of UV-induced CHS
      expression in A.majus seedlings in vivo. We define three regulatory sequence
      regions, each differing qualitatively and quantitatively in their effects on gene
      expression. Immediately upstream of the TATA box (-34) a sequence, with
      coordinates -39 to -197, functions as an orientation independent UV-light
      responsive element. The complete 1.1 kb promoter or three tandem copies of this
      element are capable of rendering a heterologous minimal promoter UV responsive.
      The next upstream region (-197 to -357) contains sequences that do not by
      themselves cause UV-induced expression, but specifically potentiate the level of
      UV-induced expression when combined with the TATA-box proximal UV-responsive
      element. A third element (-661 to -564) has the properties of a general enhancer
      since it increases the level of both uninduced and UV-induced expression.

PMID- 16453866
TI  - Cloning Knotted, the dominant morphological mutant in maize using Ds2 as a
      transposon tag.
AB  - The Kn1-2F11 mutation causes protrusions or knots along the lateral veins of the
      first few leaves of the maize plant. The phenotype is visible when an unlinked
      gene, presumably Ac, is present in the genome. The mutation is closely linked to
      a genetically unstable Adh1 mutation that resulted from the insertion of a Ds2
      element (Doring et al., 1984; Chen et al., 1986). Using a unique sequence from
      the Ds2 element as a hybridization probe, a genomic restriction fragment that
      cosegregated with the knotted phenotype was cloned. It carries the Kn1-2F11 locus
      by the following criteria. (i) Cosegregation of the fragment is tightly linked to
      the phenotype. (ii) Somatic and germinal excision produce a fragment which is the
      expected size of a revertant fragment; progeny containing the revertant size
      fragment are normal. (iii) The sequences that hybridize to this fragment are
      significantly altered in the chromosome containing the original knotted mutation,
      Kn1-O, (iv) The cloned fragment does not hybridize to a chromosome that contains
      a deletion of Kn1-O.

PMID- 16453867
TI  - Both developmental and metabolic signals activate the promoter of a class I
      patatin gene.
AB  - Patatin is one of the major soluble proteins in potato tubers and is encoded by a
      multigene family. Based on structural considerations two classes of patatin genes
      are distinguished. The 5'-upstream regulatory region of a class I gene contained
      within a 1.5 kb sequence is essential and sufficient to direct a high level of
      tuber-specific gene activity which was on average 100- to 1000-fold higher in
      tubers as compared to leaf, stem and roots in greenhouse grown transgenic potato
      plants when fused to the beta-glucuronidase reporter gene. Histochemical analysis
      revealed this activity to be present in parenchymatic tissue but not in the
      peripheral phellem cells of transgenic tubers. Furthermore the promoter fragment
      can be activated in leaves under conditions that simulate the need for the
      accumulation of starch in storage organs, i.e. high levels of sucrose. The
      expression is restricted to both mesophyll and epidermal cells in contrast to
      vascular tissue or hair cells.

PMID- 16453868
TI  - A Rhodobacter sphaeroides puf L, M and X deletion mutant and its complementation
      in trans with a 5.3 kb puf operon shuttle fragment.
AB  - A Rhodobacter sphaeroides puf L, M and X deletion mutant was constructed using
      interposon mutagenesis. The puf L, M and X genes were replaced with a kanamycin
      resistance cartridge isolated from the transposon Tn5. The deletion strain PUF
      big up tri, openLMX 21 did not grow photoheterotrophically and was resistant to
      kanamycin. Southern blot analysis of genomic DNA from the deletion strain
      confirmed that the kanamycin resistance was inserted specifically into the puf
      operon and that the L, M and X genes were deleted. A spontaneous carotenoid
      mutant of PUF big up tri, openLMX was selected and was found to accumulate
      primarily neurosporene. Spectroscopic analysis of chromatophores isolated from
      the deletion strain showed normal B875 and B800-850 expression providing further
      evidence that the photosynthetic minus phenotype was not the result of
      insertional inactivation of the promoter region of the puf operon, or the puf Q
      region. The deletion strain could be returned to the photosynthetic plus
      phenotype by complementation in trans with a 5.3 kb puf operon shuttle fragment,
      although the generation time of the complemented strain was 30% longer than wild
      type.

PMID- 16453869
TI  - A chromosome rearrangement suggests that donor and recipient sites are associated
      during Tam3 transposition in Antirrhinum majus.
AB  - We describe the structure of a chromosome rearrangement which changes the spatial
      pattern of expression of the pallida gene of Antirrhinum majus. The rearrangement
      involves a chromosome inversion of ~6 map units with one breakpoint at the end of
      a copy of the transposable element Tam3 located in the promoter region of the
      pallida locus. The sequence at the breakpoints shows that 5-7 bp, present once in
      the progenitor, has been duplicated and flanks both ends of the inversion. We
      propose that this structure arose from an aberrant Tam3 transposition, suggesting
      a model for normal transposition which involves physical association between
      donor and recipient sites. This may explain why transposition of plant
      transposable elements such as Ac in maize occurs preferentially to recipient
      sites closely linked to the donor site. Excision of the Tam3 copy located at the
      end of the chromosome inversion, results in a unique spatial pattern of pallida
      gene expression as a consequence of replacing all sequence 70 bp upstream of
      transcription by a new sequence. This pattern may be the result of deleting
      specific upstream components which regulate pallida expression and/or of changing
      the relative chromosome position of the pallida gene.

PMID- 16453870
TI  - Common components of the infection thread matrix and the intercellular space
      identified by immunocytochemical analysis of pea nodules and uninfected roots.
AB  - Three rat hybridoma cell lines have been isolated which produce monoclonal
      antibodies identifying a noduleenhanced, soluble component of Pisum sativum root
      nodules. These antibodies each recognized a protease-sensitive band (M(r) 95K) on
      SDS-polyacrylamide gels. The 95K antigen was resolved by isoelectric focusing
      into acidic and neutral components which were separately detected by AFRC MAC 236
      and MAC 265 respectively. The third antibody (MAC 204) reacted with both acidic
      and neutral components through an epitope that was sensitive to periodate
      oxidation. These monoclonal antibodies were used for immunogold localizations at
      light and electron microscopic levels. In each case, the antigen was shown to be
      present in the matrix that surrounds the invading rhizobia in infection threads
      and infection droplets, as well as in the intercellular spaces between plant cell
      walls of nodules and also of uninfected roots. By contrast, a fourth monoclonal
      antibody, AFRC JIM 5, labelled a pectic component in the walls of infection
      threads, and JIM 5 was also found to label the middle lamella of plant cell
      walls, especially at three-way junctions between cells. The composition and
      structure of the infection thread lumen is thus comparable to that of an
      intercellular space.

PMID- 16453871
TI  - Cyanide production by Pseudomonas fluorescens helps suppress black root rot of
      tobacco under gnotobiotic conditions.
AB  - Pseudomonas fluorescens CHA0 suppresses black root rot of tobacco, a disease
      caused by the fungus Thielaviopsis basicola. Strain CHA0 excretes several
      metabolites with antifungal properties. The importance of one such metabolite,
      hydrogen cyanide, was tested in a gnotobiotic system containing an artificial,
      iron-rich soil. A cyanidenegative (hcn) mutant, CHA5, constructed by a gene
      replacement technique, protected the tobacco plant less effectively than did the
      wild-type CHA0. Complementation of strain CHA5 by the cloned wild-type hcn genes
      restored the strain's ability to suppress disease. An artificial transposon
      carrying the hcn genes of strain CHA0 (Tnhcn) was constructed and inserted into
      the genome of another P.fluorescens strain, P3, which naturally does not produce
      cyanide and gives poor plant protection. The P3::Tnhcn derivative synthesized
      cyanide and exhibited an improved ability to suppress disease. All bacterial
      strains colonized the roots similarly and did not influence significantly the
      survival of T.basicola in soil. We conclude that bacterial cyanide is an
      important but not the only factor involved in suppression of black root rot.

PMID- 16453872
TI  - Reversible methylation and inactivation of marker genes in sequentially
      transformed tobacco plants.
AB  - Doubly transformed tobacco plants were obtained following sequential
      transformation steps using two T-DNAs encoding different selection and screening
      markers: T-DNA-I encoded kanamycin resistance and nopaline synthase; T-DNA-II
      encoded hygromycin resistance and octopine synthase. A genetic analysis of the
      inheritance of the selection and screening marker genes in progeny of the doubly
      tranformed plants revealed that the expression of T-DNA-I genes was often
      suppressed. This suppression could be correlated with methylation in the
      promoters of these genes. Surprisingly, both the methylation and inactivation of
      T-DNA-I genes occurred only in plants containing both T-DNAs: when self
      fertilization or backcrossing produced progeny containing only T-DNA-I,
      expression of the genes on this T-DNA was restored and the corresponding
      promoters were partially or completely demethylated. These results indicated that
      the presence of one T-DNA could affect the state of methylation and expression of
      genes on a second, unlinked T-DNA in the same genome.

PMID- 16453873
TI  - Expression of a functional monocotyledonous phytochrome in transgenic tobacco.
AB  - A chimeric oat phytochrome structural gene with an uninterrupted coding region
      was constructed for expression of the monocot protein in transgenic plants. The
      structural gene was placed under the transcriptional control of either a light
      regulated oat phytochrome promoter or the constitutively active cauliflower
      mosaic virus 35S promoter. These genes were then introduced into Nicotiana
      tabacum and N.plumbaginifolia. None of the regenerated plants showed expression
      of oat phytochrome RNA when transcription was controlled by the oat promoter. In
      contrast, RNA was obtained in plants when the structural gene was functionally
      linked to the 35S promoter. Transformants expressing oat phytochrome RNA produced
      a full length 124-kd polypeptide that was recognized by oat-specific anti
      phytochrome monoclonal antibodies. The oat protein was a substrate for
      chromophore addition in tobacco as judged by its red/far-red photoreversible
      sensitivity to trypsin degradation. Production of oat phytochrome in transgenic
      plants gave rise to increased phytochrome spectral activity in both light- and
      dark-grown plants. This increased phytochrome content resulted in phenotypic
      changes in transformed plants, including semi-dwarfism, darker green leaves,
      increased tillering and reduced apical dominance. The possible significance of
      expressing a biologically active phytochrome in transgenic plants is discussed.

PMID- 16453875
TI  - Resistance to the photosystem II herbicide diuron is dominant to sensitivity in
      the cyanobacterium Synechococcus sp. PCC7942.
AB  - The transformable cyanobacterium, Synechococcus sp. PCC7942, was used to study
      the genetics of resistance to the herbicide diuron. In wild-type cells, diuron
      binds to one of the core proteins, called D1, of photosystem II reaction centres.
      This binding prevents the transfer of electrons from Q(A), the primary quinone
      acceptor, to Q(B), which is necessary to create the charge separation that drives
      ATP synthesis. A single amino acid substitution in the D1 protein reduces diuron
      binding and confers herbicide resistance to reaction centres containing the
      substituted D1 protein. In Synechococcus 7942, the D1 protein is encoded by three
      functional genes called psbAI, psbAII and psbAIII. By selectively altering one
      member at a time of the three-member psbA gene family, we have demonstrated that
      diuron-resistant alleles are dominant to diuron-sensitive alleles. The relative
      abundance of the different psbA gene transcripts is correlated with the fraction
      of diuron-resistant reaction centres and with the degree of diuron resistance.
      Growth in sublethal diuron selectively increases the steady-state levels of
      transcripts of genes (psbA and psbD) encoding the core proteins of photosystem
      II. We have also found that turnover of the D1 protein can be uncoupled from
      electron transport through photosystem II.

PMID- 16453874
TI  - Maize streak virus genes essential for systemic spread and symptom development.
AB  - The entire genome of single component geminiviruses such as maize streak virus
      (MSV) consists of a single-stranded circular DNA of ~2.7 kb. Although this size
      is sufficient to encode only three average sized proteins, the virus is capable
      of causing severe disease of many monocots with symptoms of chlorosis and
      stunting. We have identified viral gene functions essential for systemic spread
      and symptom development during MSV infection. Deletions and gene replacement
      mutants were created by site-directed mutagenesis and insertion between flanking
      MSV or reporter gene sequences contained in Agrobacterium T-DNA derived vectors.
      Following Agrobacterium-mediated inoculation of maize seedlings, the mutated MSV
      DNAs were excised from these binary vectors by homologous recombination within
      the flanking sequences. Our analyses show that the capsid gene of MSV, while not
      required for replication, is essential for systemic spread and subsequent disease
      development. The ;+' strand open reading frame (ORF) located immediately upstream
      from the capsid ORF and predicted to encode a 10.9 kd protein was also found to
      be dispensable for replication but essential for systemic spread. By this
      analysis, MSV sequences that support autonomous replication were localized to a
      1.7 kb segment containing the two viral intergenic regions and two overlapping
      complementary ;-' strand ORFs. Despite the inability of the gene replacement
      mutants to spread systemically, both inoculated and newly developed leaves
      displayed chlorotic patterns similar to the phenotype observed in certain
      developmental mutants of maize. The similarity of the MSV mutant phenotype to
      these developmental mutants is discussed.

PMID- 16453876
TI  - Corrigendum: DNA rearrangement of a homeobox gene in myeloid leukaemic cells.
AB  - [This corrects the article on p. 4283 in vol. 7.].

PMID- 16453877
TI  - Erratum: A chromosome rearrangement suggests that donor and recipient sites are
      associated during Tam3 transposition in Antirrhinum majus.

PMID- 16453878
TI  - Erratum: The Escherichia coli lov gene product connects peptidoglycan synthesis,
      ribosomes and growth rate.
AB  - [This corrects the article on p. 317 in vol. 8, PMID: 2540960.].

PMID- 16453880
TI  - Vascular expression of a bean cell wall glycine-rich protein-beta-glucuronidase
      gene fusion in transgenic tobacco.
AB  - In French bean (Phaseolus vulgarisL.), the glycine-rich wall protein GRP 1.8 is
      specifically synthesized in protoxylem tracheary elements of the vascular system.
      A 494 bp upstream promoter fragment of the gene encoding GRP 1.8 was isolated and
      translationally fused to the beta-glucuronidase reporter gene. Transgenic tobacco
      plants containing this construct expressed the gene in vascular tissue of roots,
      stems, leaves and flowers. The gene was developmentally expressed during
      differentiation of both primary and secondary vascular tissue and was also
      rapidly induced (in < 30 min) after excision-wounding of young stems. This wound
      response is more rapid than in bean hypocotyls, indicating possible differences
      between the activation mechanism for glycine-rich protein gene expression in
      wounded bean and tobacco. Only a subset of cells were found to participate in the
      wound response. In young stems, the GRP wound induction was localized in pith
      parenchyma cells adjacent to the wound surface, where vessel regeneration is
      known to occur. Thus, a promoter fragment of 494 bp, including 427 bp upstream
      from the transcription start site, contains information for tissue-specific and
      wound-induced gene regulation. The cell-type specificity of expression suggests
      that the GRP 1.8 promoter is regulated by very specific developmental and
      environmental signals.

PMID- 16453881
TI  - Transpositional behavior of the maize En/Spm element in transgenic tobacco.
AB  - The transposable element Enhancer (En/Spm) of Zea mays encodes the functions
      necessary for transposition of members of the En-I family of elements. En
      constructs were introduced into tobacco and transposition was demonstrated by
      cloning and DNA sequence analysis. Transcriptional analysis of En transgenic
      plants revealed 2.5 and 6 kb En homologous transcripts similar in size to those
      found in maize, in addition to aberrant splice products. Progeny analysis of a
      primary transformant indicates En transpositional activity after meiosis. In
      these progeny somatic variegation, at the NPT II gene, was demonstrated to be
      caused by En excision. Two re-insertions of En were analyzed and found to reside
      in unique copy DNA while another was found in middle repetitive DNA.

PMID- 16453882
TI  - Both wound-inducible and tuber-specific expression are mediated by the promoter
      of a single member of the potato proteinase inhibitor II gene family.
AB  - A chimeric gene consisting of 1.3 kb of the 5' regulatory region of a member of
      the potato proteinase inhibitor II gene family, the coding region of the
      bacterial beta-glucuronidase (GUS) gene and 260 bp of the proteinase inhibitor II
      3'-untranslated region containing the poly(A) addition site was introduced into
      potato and tobacco by Agrobacterium tumefaciens mediated transformation. Analysis
      of transgenic plants demonstrates systemic, wound-inducible expression of this
      gene in stem and leaves of potato and tobacco. Constitutive expression was found
      in stolons and tubers of non-wounded potato plants. Histochemical experiments
      based on the enzymatic activity of the GUS protein indicate an association of the
      proteinase inhibitor II promoter activity with vascular tissue in wounded as well
      as in systemically induced non-wounded leaves, petioles, potato stems and in
      developing tubers. These data prove that one single member of the proteinase
      inhibitor II gene family contains cis-active elements, which are able to respond
      to both developmental and environmental signals. Furthermore they support the
      hypothesis of an inducing signal (previously called proteinase inhibitor inducing
      factor), which is released at the wound site and subsequently transported to non
      wounded parts of the plant via the vascular system from where it is released to
      the surrounding tissue.

PMID- 16453883
TI  - Positive and negative control of nod gene expression in Rhizobium meliloti is
      required for optimal nodulation.
AB  - We show that expression of common nodulation genes in Rhizobium meliloti is under
      positive as well as negative control. A repressor protein was found to be
      involved in the negative control of nod gene expression. Whereas the activator
      NodD protein binds to the conserved cis-regulatory element (nod-box) required for
      coordinated regulation of nod genes, the repressor binds to the overlapping nodD1
      and nodA promoters, at the RNA polymerase binding site. A model depicting the
      possible interaction of the plant-derived nod gene inducer (luteolin), the NodD
      and the repressor with the nod promoter elements is presented. Mutants lacking
      the repressor exhibited delayed nodulation phenotype, indicating that fine tuning
      of nod gene expression is required for optimal nodulation of the plant host.

PMID- 16453885
TI  - EMBO members in North America.

PMID- 16453884
TI  - Mobilization of the gypsy and copia retrotransposons in Drosophila melanogaster
      induces reversion of the ovo dominant female-sterile mutations: molecular
      analysis of revertant alleles.
AB  - The ovo locus is required for the maintenance of the female germ line in
      Drosophila melanogaster. In the absence of an ovo gene, males are completely
      normal but females have no germ-line stem cells. Three dominant mutations at the
      ovo locus, called ovo, were observed to revert towards recessive alleles at high
      frequency when ovo males were crossed to females of the strain y v f mal. We have
      found that this strain contains an inordinately high number of gypsy transposable
      elements, and crossing it with the ovo strains results in the mobilization of
      both gypsy and copia, with high-frequency insertions into the ovo locus: of 16
      revertants examined 12 have gypsy and four have copia inserted at 4E, the ovo
      cytological site. Using gypsy DNA as a tag we have cloned 32 kb of wild-type DNA
      sequences surrounding a gypsy insertion and characterized molecular
      rearrangements in several independent revertants: in 10 of them gypsy appears to
      be inserted into the same site. The orientation of gypsy is strictly correlated
      with whether the neighbouring lozenge-like mutation appears in the revertants. A
      distal limit of the ovo locus was molecularly determined from the breakpoint of a
      deletion affecting closely flanking regions.

PMID- 16453886
TI  - New EMBO members elected in the 1989 ballot.

PMID- 16453887
TI  - Erratum: Identification of the gene for fly non-muscle myosin heavy chain:
      Drosophila myosin heavy chains are encoded by a gene family.
AB  - [This corrects the article on p. 913 in vol. 8, PMID: 2498088.].

PMID- 16453888
TI  - Erratum: Common components of the infection thread matrix and the intercellular
      space identified by immunocytochemical analysis of pea nodules and uninfected
      roots.

PMID- 16453890
TI  - A wheat alpha-Amy2 promoter is regulated by gibberellin in transformed oat
      aleurone protoplasts.
AB  - Gibberellin (GA(3))-responsive aleurone protoplasts isolated from Avena sativa
      have been successfully used as a transient expression system to analyse promoter
      fusions between the wheat alpha-amylase gene alpha-Amy2/54 and the reporter gene
      GUS. Following PEG-mediated uptake of plasmid DNA, transient expression directed
      by the alpha-Amy2/54 promoter was found to be regulated in the same way as the
      endogenous oat alpha-amylase genes. Expression was thus dependent on the
      inclusion of GA(3) in the protoplast incubation media, could not be detected
      before a lag phase of 2 days following transformation and was inhibited by
      simultaneous addition of abscisic acid (ABA) with GA(3) to the media. In
      contrast, expression from the CaMV 35S promoter in the same system was not
      affected by GA(3) or ABA and could be detected 1 day after transformation.
      Introduction of a further three different promoters into the aleurone protoplasts
      confirmed that GA(3) specifically controlled transient expression from the alpha
      Amy2/54 promoter only. Promoter deletions of the alpha-Amy2/54: GUS fusion
      demonstrated that sequences within 300 bp of the start of transcription of the
      gene were sufficient to direct high-level expression that was regulated by GA(3)
      and ABA.

PMID- 16453892
TI  - The human haptoglobin gene promoter: interleukin-6-responsive elements interact
      with a DNA-binding protein induced by interleukin-6.
AB  - [This corrects the article on p. 1145 in vol. 8, PMID: 2787245.].

PMID- 16453891
TI  - Proximal-distal pattern formation in Drosophila: cell autonomous requirement for
      Distal-less gene activity in limb development.
AB  - Limb development in the Drosophila embryo requires a pattern-forming system to
      organize positional information along the proximal-distal axis of the limb. This
      system must function in the context of the well characterized anterior-posterior
      and dorsal-ventral pattern-forming systems that are required to organize the body
      plan of the embryo. By genetic criteria the Distal-less gene appears to play a
      central role in limb development. Lack-of-function Distal-less mutations cause
      the deletion of a specific subset of embryonic peripheral sense organs that
      represent the evolutionary remnants of larval limbs. Distal-less activity is also
      required in the imaginal discs for the development of adult limbs. This
      requirement is cell autonomous and region specific within the developing limb
      primordium. Production of genetically mosaic imaginal discs, in which clones of
      cells lack Distal-less activity, indicates the existence of an organized proximal
      distal positional information in very young imaginal disc primordia. We suggest
      that this graded positional information may depend on the activity of the Distal
      less gene.

PMID- 16453893
TI  - Corrigenda: An ice nucleation reporter gene system: identification of inducible
      pathogenicity genes in Pseudomonas syringae pv. phaseolicola.
AB  - [This corrects the article on p. 1291 in vol. 8, PMID: 2548841.].

PMID- 16453895
TI  - NEW PRODUCT NEWS FROM HOEFER: New 24 Place Slot-Blotting Manifold Allows
      Individual Collection Of Filtrate.

PMID- 16453894
TI  - Erratum: Endocytosis and recycling of the fibronectin receptor in CHO cells.
AB  - [This corrects the article on p. 1341 in vol. 5.].

PMID- 16453896
TI  - The CaMV 35S enhancer contains at least two domains which can confer different
      developmental and tissue-specific expression patterns.
AB  - We have analyzed expression conferred by two domains from the cauliflower mosaic
      virus (CaMV) 35S promoter and found different patterns in seeds, seedlings and
      seven week old plants. Expression from domain A (-90 to +8) is strongest in the
      radicle of the embryo, the radicle pole of the endosperm and in root tissue of
      seedlings and mature plants. Expression from domain B (-343 to -90) is strongest
      in the cells adjacent the cotyledon of the endosperm, in the cotyledons of the
      embryo and seedings and in the leaves and stem of mature plants. When both domain
      A and domain B are present expression is detectable in most tissues at all stages
      of development. Thus analysis of a constitutive promoter in transgenic plants can
      be used to identify cis elements that confer tissue specific and developmentally
      regulated expression.

PMID- 16453897
TI  - ATP-dependent import of a lumenal protein by isolated thylakoid vesicles.
AB  - The 33 kd protein of the photosynthetic oxygen-evolving complex is synthesized in
      the cytoplasm as a larger precursor and transported into the thylakoid lumen via
      a stromal intermediate form. In this report we describe a reconstituted system in
      which the later stages of this import pathway can be studied in isolation. We
      demonstrate import of the 33 kd protein, probably as the intermediate form, into
      isolated pea thylakoids by a mechanism which is stimulated by the addition of
      ATP. The imported protein is processed to the mature size and is resistant to
      digestion by proteases. The thylakoidal protein transport system is specific in
      that non-chloroplast proteins and precursors of stromal proteins are not
      imported.

PMID- 16453898
TI  - Notes added.

PMID- 16453899
TI  - Corrigendum: Antibody engineering for the analysis of affinity maturation of an
      anti-hapten response.
AB  - [This corrects the article on p. 1995 in vol. 7.].

PMID- 16453900
TI  - Clonal recruitment and somatic mutation in the generation of immunological memory
      to the hapten NP.
AB  - [This corrects the article on p. 2459 in vol. 5.].

PMID- 16453901
TI  - New product news from hoefer: DNA analysis news.

PMID- 16453903
TI  - Note added.

PMID- 16453906
TI  - Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution
      in the CAGYC region of the beta-subunit.
AB  - [This corrects the article on p. 2291 in vol. 8, PMID: 2792087.].

PMID- 16453904
TI  - Erratum: Proximal-distal pattern formation in Drosophila: cell autonomous
      requirement for Distal-less gene activity in limb development.
AB  - [This corrects the article on p. 2045 in vol. 8.].

PMID- 16453907
TI  - Corrigenda: Mapping of Digitaria streak virus transcripts reveals different RNA
      species from the same transcription unit.
AB  - [This corrects the article on p. 1033 in vol. 8, PMID: 2472960.].

PMID- 16453908
TI  - Transient induction of IL-2 receptor in cultured T cell lines by HTLV-1 LTR
      linked tax-1 gene.
AB  - [This corrects the article on p. 1953 in vol. 8, PMID: 2792077.].

PMID- 16453909
TI  - NEW PRODUCT NEWS FROM HOEFER: A New Mighty Smalltrade mark Unit For Running
      Taller Gels.

PMID- 16453911
TI  - Corrigendum: Differential expression of myogenic determination genes in muscle
      cells: possible autoactivation by the Myf gene products.
AB  - [This corrects the article on p. 3617 in vol. 12.].

PMID- 16453912
TI  - Errata: Characterization of the RNA polymerases of Trypanosoma brucei:
      trypanosomal mRNAs are composed of transcripts derived from both RNA polymerase
      II and III.
AB  - [This corrects the article on p. 3383 in vol. 8, PMID: 2583103.].

PMID- 16453913
TI  - Proper expression of myosin genes in transgenic nematodes.
AB  - [This corrects the article on p. 3419 in vol. 8, PMID: 2583105.].

PMID- 16453914
TI  - Eight tips for managing diabetes distress.

PMID- 16453915
TI  - Vegetarian meal plan. Beneficial for type 2 diabetes?

PMID- 16453916
TI  - Healthy aging with diabetes.

PMID- 16453917
TI  - Eating across America. Cajun and Creole cuisine.

PMID- 16453918
TI  - Teaming up for better diabetes control.

PMID- 16453919
TI  - Exenatide. From the Gila monster to you. Exenatide is the first of a new class of
      drugs known as "incretin mimetics" that can enhance your blood glucose control.

PMID- 16453920
TI  - Tools and techniques for visual impairment.

PMID- 16453921
TI  - For parents. Getting eating habits on a healthy track.

PMID- 16453922
TI  - Diabetes quiz. How much do you know about your liver?

PMID- 16453923
TI  - Supermarket smarts. Frozen pizza.

PMID- 16453924
TI  - Women & diabetes. Preventing coronary heart disease.

PMID- 16453925
TI  - Diabetes resources. Volunteering.

PMID- 16453926
TI  - Try the cocktail.

PMID- 16453927
TI  - Taking stock.

PMID- 16453929
TI  - Hands across the bridge.

PMID- 16453928
TI  - HIV in the eye of the storm.

PMID- 16453930
TI  - Friends of people living with HIV/AIDS.

PMID- 16453931
TI  - Resistance exercise helps heart failure patients.

PMID- 16453932
TI  - Two osteoporosis treatments deemed best for brittle bones. Sequential therapy of
      two drugs, bisphosphonates and PTH, produces the best effects on bone strength.

PMID- 16453933
TI  - Diet + exercise best for knee OA.

PMID- 16453934
TI  - Hearing impairment can affect your overall health. Hearing loss can lead to
      depression and isolation. But new hearing aids and cochlear implants offer hope.

PMID- 16453935
TI  - Antioxidants reduce risk of macular degeneration.

PMID- 16453936
TI  - Setting the record straight: five cancer myths debunked. Cancer experts talk
      about the most common cancer myths--and why they are erroneous.

PMID- 16453937
TI  - Soy food: a boon for aging bones. Tofu, soy milk, or other soy-based foods taken
      daily are shown to cut fracture risk in postmenopausal women.

PMID- 16453938
TI  - Kind of meat eaten may increase risk of colon polyps.

PMID- 16453940
TI  - Heartfelt Valentine chocolates.

PMID- 16453939
TI  - Pulmonary risks; the latest on lung cancer. Smokers and nonsmokers both need to
      know that genetics play a role, food can be a preventative, and new tests can
      lead to earlier diagnosis.

PMID- 16453941
TI  - I have been diagnosed with a poor ejection fraction from my left ventricle. What
      does that mean, and what medications would be most beneficial?

PMID- 16453942
TI  - Risk of cervical cancer still high despite removal of pre-cancerous cells.

PMID- 16453944
TI  - Celiac disease.

PMID- 16453943
TI  - An unusual cause of acquired Brown's syndrome.

PMID- 16453945
TI  - Acute Lung Injury/Adult Respiratory Distress Syndrome. Proceedings from the 3rd
      Annual Pittsburgh International Lung Conference, Farmington, Pennsylvania, USA,
      October 16-20, 2004.

PMID- 16453946
TI  - Esthetic evaluation of immediate breast reconstruction after nipple-sparing or
      skin-sparing mastectomy.
AB  - BACKGROUND: It has been reported that immediate autologous tissue breast
      reconstruction after nipple-sparing mastectomy (NSM) or skin-sparing mastectomy
      (SSM) is esthetically superior to autologous tissue reconstruction after
      conventional mastectomy (CM). We evaluated reconstructed breasts to determine
      whether these methods contribute to breast appearance other than skin texture.
      METHODS: Between April 1992 and September 2001, forty-two patients underwent
      immediate breast reconstruction using autologous tissue. Mastectomy options were
      NSM, SSM and CM. Postoperative photographs were evaluated using a subscale
      (volume, contour, placement, and inframammary fold) on a 0-2 point scale. Sternal
      notch to nipple distances of the affected and normal sides were measured with
      photographs to estimate nipple-areola complex (NAC) position. No corrective
      procedure was performed in a later phase before evaluation. RESULTS: NSM was
      performed in 22, SSM in 6 and CM in 14 cases. On esthetic evaluation, the NSM and
      SSM groups received 4.96 and the CM group received 4.63. There were no
      significant differences. In the NSM and SSM group, the NAC position rose in cases
      with partial necrosis or fat lysis compared with the no complication group (p =
      0,004). CONCLUSIONS: Autologous tissue breast reconstruction after NSM or SSM is
      esthetically equal to autologous tissue reconstruction after CM with regard to
      parameters other than skin texture. Preserved or simultaneously reconstructed NAC
      sometimes emphasizes nipple-areola asymmetry when breast deformity has occurred.

PMID- 16453947
TI  - Understanding trust and confidence: two paradigms and their significance for
      health and social care.
AB  - Trusting agents characteristically anticipate beneficial outcomes, under
      conditions of uncertainty, in their engagement with others. However, debates
      about trust incorporate different interpretations of risk, uncertainty,
      calculation, affect, morality and motivation in explaining when trust is
      appropriate and how it operates. This article argues that discussions about trust
      have produced a concept without coherent boundaries and with little operational
      value. Two paradigms are identified, which distinguish the characteristics of
      trust and confidence. It is argued that a reliance on confidence in human affairs
      makes trust redundant and that this has undesirable moral consequences.
      Discussion is illustrated by the UK Government's 'modernisation' policy in health
      and social care, which privileges confidence in systems over trust in moral
      agents.

PMID- 16453948
TI  - Slaves, embryos, and nonhuman animals: moral status and the limitations of common
      morality theory.
AB  - Common morality theory must confront apparent counterexamples from the history of
      morality, such as the widespread acceptance of slavery in prior eras, that
      suggest core norms have changed over time. A recent defense of common morality
      theory addresses this problem by drawing a distinction between the content of the
      norms of the common morality and the range of individuals to whom these norms
      apply. This distinction is successful in reconciling common morality theory with
      practices such as slavery, but only at the cost of underscoring the limits of
      common morality theory, in particular its inability to resolve disputes about the
      moral status of entities. Given that many controversies in bioethics center on
      the disputed status of various entities, such as embryos and nonhuman animals,
      this is an important limitation. Nonetheless, common morality theory still can be
      a useful resource in diminishing moral conflict on issues that do not involve
      disputes over moral status.

PMID- 16453952
TI  - Small punch biopsies don't require sutures.

PMID- 16453949
TI  - At the edge of humanity: human stem cells, chimeras, and moral status.
AB  - Experiments involving the transplantation of human stem cells and their
      derivatives into early fetal or embryonic nonhuman animals raise novel ethical
      issues due to their possible implications for enhancing the moral status of che
      chimeric individual. Although status-enhancing research is not necessarily
      objectionable from the perspective of the chimeric individual, there are grounds
      for objecting to it in the conditions in which it is likely to occur. Translating
      this ethical conclusion into a policy recommendation, however, is complicated by
      the fact that substantial empirical and ethical uncertainties remain about which
      transplants, if any, would significantly enhance the chimeric individual's moral
      status. Considerations of moral status justify either an early-termination policy
      on chimeric embryos, or, in the absence of such a policy, restrictions on the
      introduction of pluripotent human stem cells into early-stage developing animals,
      pending the resolution of those uncertainties.

PMID- 16453953
TI  - Acellular pertussis vaccine 63% to 92% effective.

PMID- 16453954
TI  - Pseudoephedrine has a minimal effect on blood pressure.

PMID- 16453955
TI  - Light therapy for SAD effective short-term.

PMID- 16453956
TI  - Swallowed coins: waiting equal to immediate removal.

PMID- 16453957
TI  - The day the world changed; or, how we "got into the game".

PMID- 16453959
TI  - Correction: Notice of duplicate publication.

PMID- 16453958
TI  - [Problems related to water metabolism in view of host responses--with special
      reference to antidiuretic hormones from the posterior hypothalamus (a
      psychophysiological study on emotions)].

PMID- 16453960
TI  - Acceptance, avoidance, and ambiguity: conflicting social values about childhood
      disability.
AB  - Advances in medical technology now permit children who need ventilator assistance
      to live at home rather than in hospitals or institutions. What does this
      ventilator-dependent life mean to children and their families? The impetus for
      this essay comes from a study of the moral experience of 12 Canadian families-
      parents, ventilator-dependent child, and well siblings. These families express
      great love for their children, take on enormous responsibilities for care, live
      with uncertainty, and attempt to create "normal" home environments. Nevertheless,
      they experience social isolation, sometimes even from their extended families and
      health care providers. Their lives are constrained in many ways. The challenges
      faced by parents of technology-dependent children raise questions of justice
      within society and within families.

PMID- 16453961
TI  - Dana-Farber Cancer Institute ethics rounds: life-threatening illness and the
      desire to adopt.
AB  - Originally presented during Ethics Rounds at the Dana-Farber Cancer Institute,
      this commentary on the case of a patient treated for life-threatening cancer
      explores the responsibilities of health care providers when addressing the
      patient's desire to adopt a child.

PMID- 16453962
TI  - Suggests alternate diagnosis in dog with tibial tumor.

PMID- 16453963
TI  - Questions accuracy in study of metal plate implants.

PMID- 16453964
TI  - Intraoperative anaphylaxis: verba volant, scripta manent!
AB  - We describe a case of intraoperative gelatine-induced anaphylaxis whose diagnosis
      was delayed as the use of gelatine during surgical procedures was omitted for two
      times in patient's medical records. The subject is a 66-year old woman, with a
      negative medical history of atopy, food and drug allergy, with arterial
      hypertension on a course of beta-blockers and with bladder carcinoma requiring
      surgery. The patient had tolerated both general and local anaesthesia on several
      previous occasions. On the first occasion she experienced arterial fibrillation
      secondary to a severe episode of hypotension following local anaesthesia, while
      on a course of beta-blockers. On the second occasion she developed a very severe
      episode of hypotension followed by the outbreak of a generalised rash during
      general anaesthesia. The tryptase sera level was 109 mg/L one hour after the
      reaction had subsided, while the basal values were normal. On the third occasion
      the patient redeveloped severe hypotension and a generalised rash during general
      anaesthesia. The allergological work-up was negative, except for intradermal test
      with gelatine. A study of the intra-cellular cytokines in blood lymphocytes
      showed a production of IL4 from CD4+ lymphocytes after stimulation by gelatine.
      The patient underwent a successive surgical procedure without any adverse event.

PMID- 16453965
TI  - The dilemma of the negative skin test reactors with a history of venom
      anaphylaxis: will this always be the case?
AB  - The loss of sensitization over time, the involvement of a different pathogenetic
      mechanism and the poor sensitivity of diagnostic tests have been included among
      the causes of a non IgE-mediated anaphylaxis triggered by an insect sting. To
      provide further insight into this topic we describe the case of a patient
      suffering from urticaria pigmentosa, anaphylactic shock due to a Vespid sting and
      monosensitive to Polistes dominulus venom, who was previous diagnosed with non
      IgE mediated insect sting anaphylaxis in subjects with urticaria pigmentosa.
      Therefore ultra-rush specific immunotherapy using an acqueous Polistes dominulus
      venom extract was performed over two mornings until a total dose of 100mcg was
      reached without any side effects. Presently the patient is undergoing maintenance
      therapy with a depot Polistes dominulus venom extract at 4-weekly intervals and
      is free of side effects. In conclusion, despite the high cross-reactivity among
      the venoms of the various species of Polistes, recent evidence of a selective
      specificity unique to European Polistes allergens raises the problem of the need
      to make the American Polistes venom as well as that of Polistes dominulus (a very
      common insect in Europe) available both for diagnostic and therapeutic purposes.
      Besides the fact that the presence of urticaria pigmentosa alone could have
      explained the anaphylactic reaction to the aspecific stimulation triggered by the
      venom, this case history also demonstrates that omitting to perform skin tests
      for Polistes dominulus venom would have led to the same misdiagnosis of non IgE
      mediated anaphylaxis and served only to further delay commencing specific
      immunotherapy.

PMID- 16453966
TI  - A case of fatal biphasic anaphylaxis secondary to multiple stings: adrenalin
      and/or a longer observation time could have saved the patient?
AB  - We report the case of an atopic male, 76 years old, with post-myocardial
      infarction ischaemic cardiopathy, arterial hypertension and a history of insect
      sting induced large local reactions who died because of a biphasic anaphylaxis
      subsequent to multiple Vespid stings (about 15). Within approximately ten minutes
      after the stings he developed urticaria, extended erythema and hypotension (90/60
      mmHg), measured by a family member. The objective physical examination by the
      emergency doctor at the patient's home revealed an orticarioid reaction and
      erythema of the back and neck, an unaffected respiratory apparatus and CNS,
      normal pupils, a pulse rate of 74, normal blood pressure ranging from 120/70 to
      130/60 mmHg. The patient was administered antihistamine and corticosteroid
      through parenteral route. During the 45' observation period at the patient's home
      the urticaria subsided but not to completion. Approximately 40 minutes after the
      emergency doctor left, the urticaria reoccurred, angioedema of the neck and
      worsening asthenia developed. The patient died, despite attempts to resuscitate
      him by the emergency doctor that had been called out again. A post-mortem
      examination revealed generalised eodema of the lungs, brain, glottis, and bowels
      due to the severe characteristic systemic compromise of anaphylaxis. The Authors
      discuss whether an early use of adrenalin and/or a longer observation time could
      have saved the patient.

PMID- 16453967
TI  - Analysis of the positivity rate in IgE positive patients to food allergens in
      Verona Hospital laboratory during 2003.
AB  - BACKGROUND: It has been known for some time now that reactions to allergens, not
      only those inhaled but also those in food, varies with age in atopical patients.
      OBJECTIVE: To evaluate the specific IgE positivity percentage in order to improve
      laboratory diagnosis in subjects with suspected food allergy. METHODS: The
      positivity percentages of specific IgE were analysed (UniCAP100-Pharmacia) taking
      into consideration the two age brackets of below and above 12 years. The below 12
      years age bracket was then further divided into pre-school age (3-5 years) and
      school age (6-12 years). RESULTS: By measuring the simple positivity percentage
      for specific IgE to food allergens, there is a clear decrease as the child
      matures in reactions to milk and eggs and an increase towards food IgEs that
      cross-react with grass and tree pollens or other inhaled allergens like moulds
      and mites. CONCLUSION: It will be necessary in the future to have the diagnostic
      means to identify this cross-reaction problem by using recombinant allergens that
      can demonstrate the combined reaction between inhaled and food allergens.

PMID- 16453968
TI  - Sensitization to horse allergens without apparent exposure to horse. Report of
      two cases.
AB  - It has been well established that occupational exposure to horses increases the
      risk of allergic sensitization to horse hair, on the contrary very few data have
      been published in individuals without direct contact with horses. We describe two
      cases of severe respiratory symptoms triggered by a single direct exposure in two
      patients with only 4-5 previous short contacts with horses during the entire
      their life, since they live in urban area of Naples. Cutaneous and serological
      diagnostic tests showed significant sensitization to horse dander other than some
      common inhalant allergens. Our report suggests that, in already (but unaware)
      horse-sensitized patients, the last direct contact with a horse has triggered
      severe respiratory symptoms. Passive carriage of horse allergen by the clothes of
      individuals in contact with horses/horse environments or a cross-reactivity
      between horse allergen (a lipocalin) and the major allergens (also lipocalins) of
      several furred animals are likely to explain our findings. Some other
      considerations can be derived by the clinical observation. First, it is likely
      that allergic sensitization to horse allergens could be more frequent than
      expected also in subjects without direct exposure to horse because of living in
      urban areas. Secondly, individuals suspected to be highly atopic or those already
      sensitized to some pet dander should be tested by SPTs/radio-allergo-sorbent test
      before the introduction of a pet indoors or, in the case of a big animal as the
      horse, a direct horse contact/entering into environments containing a horse.

PMID- 16453969
TI  - Effects on symptoms and quality of life of hypertonic saline nasal spray added to
      antihistamine in persistent allergic rhinitis--a randomized controlled study.

PMID- 16453971
TI  - Health care spending shows signs of slowing.

PMID- 16453970
TI  - Methodology and potential pitfalls in allergic diseases study designs:
      measurements for the assessment of the overall severity of atopic dermatitis--the
      four step severity score (FSSS), SCORAD-related, electronic system, for the
      simple and rapid evaluation of the skin and mucosal allergic inflammation.
AB  - Medical statistics may contribute to ameliorate research by improving the design
      of studies and identifying the optimal method for the analysis of results.
      Sometimes, nevertheless, it could be misemployed flawing the benefit potential.
      Allergic diseases pathogenesis is recognized to be systemic but global
      initiatives such as GINA and ARIA documents define allergic asthma and rhinitis
      as organ diseases; such an asymmetrical view raises a set of known and unknown
      confounding that could influence the quality of the process of evidence-based
      decision-making (topic symptomatic therapeutic interventions versus systemic
      pathogenetic interventions). This article shows the first scoring system for the
      assessment of atopic dermatitis lesions developed in the allergy-area. A four
      step severity score (FSSS) was chosen in agreement with those developed for
      asthma and rhinitis in global initiatives, to avoid any further differences in
      evaluating the severity of allergic diseases. FSSS relates each step with the
      objective signs of the SCORAD and rates the disease course as intermittent or
      persistent. A devoted electronic program has been also framed to allow a quick
      and simple contemporary evaluation of the SCORAD Index (Section I) and of the
      FSSS (Section II); the program furthermore foresees a third section named ESAS
      (Extra Skin Allergic Signs) (Section III) in which it is possible to check
      whether organs other than the skin are involved by the allergic inflammation. The
      limitations potential generated by a misemployment of medical statistics for
      clinical trials designed to establish benefits rising from specific immunotherapy
      for allergic diseases have been also discussed extensively.

PMID- 16453972
TI  - Vague claims data challenge therapy trends and coverage.

PMID- 16453973
TI  - Sleep of aging women and men: back to basics.

PMID- 16453974
TI  - Hypersynchronous slow delta, cyclic alternating pattern and sleepwalking.

PMID- 16453975
TI  - Did fat boy Joe need hormone replacement?

PMID- 16453976
TI  - Searching for the countermeasure of night-shift sleepiness.

PMID- 16453977
TI  - Gender (sex) and sleep: shh. . . not in front of the children.

PMID- 16453978
TI  - Short nights reduce light-induced circadian phase delays in humans.
AB  - STUDY OBJECTIVE: Short sleep episodes are common in modern society. We recently
      demonstrated that short nights reduce phase advances to light. Here we show that
      short nights also reduce phase delays to light. DESIGN: Two weeks of 6-hour sleep
      episodes in the dark (short nights) and 2 weeks of long 9-hour sleep episodes
      (long nights) in counterbalanced order, separated by 7 days. Following each
      series of nights, there was a dim-light phase assessment to assess baseline
      phase. Three days later, subjects were exposed to a phase-delaying light stimulus
      for 2 days, followed by a final phase assessment. SETTING: Subjects slept at home
      in dark bedrooms but came to the laboratory for the phase assessments and light
      stimulus. PARTICIPANTS: Seven young healthy subjects. INTERVENTIONS: The 3.5-hour
      light stimulus was four 30-minute pulses of bright light (-5000 lux) separated by
      30-minute intervals of room light. The stimulus began 2.5 hours after each
      subject's dim-light melatonin onset, followed by a 6- or 9-hour sleep episode. On
      the second night, the bright light and sleep episode began 1 hour later.
      MEASUREMENTS AND RESULTS: The dim-light melatonin onset and dimlight melatonin
      offset phase delayed 1.4 and 0.7 hours less in the short nights, respectively
      (both p < or = .015). CONCLUSIONS: These results indicate for the first time that
      short nights can reduce circadian phase delays, that long nights can increase
      phase delays to light, or both. People who curtail their sleep may inadvertently
      reduce their circadian responsiveness to evening light.

PMID- 16453979
TI  - Glucocorticoid receptor-dependent desensitization of 5-HT1A autoreceptors by
      sleep deprivation: studies in GR-i transgenic mice.
AB  - Sleep deprivation for one night induces mood improvement in depressed patients,
      an action that probably involves the serotonergic (5-HT) system. In animals,
      sleep deprivation and pharmacologic treatment with antidepressants exert similar
      effects on 5-HT neurotransmission, notably functional desensitization of 5-HT1A
      autoreceptors located on 5-HT neurons in the dorsal raphe nucleus (DRN). However,
      in stressful conditions, corticosterone can also induce a desensitization of
      these autoreceptors. STUDY OBJECTIVES: To investigate the mechanisms of this
      adaptation during sleep deprivation and the possible involvement of
      corticosterone, we studied the effects of an 18-hour sleep deprivation, by forced
      locomotion, on 5-HT1A receptor-mediated firing response of DRN 5-HT neurons in
      transgenic mice with impaired glucocorticoid-receptor expression (GR-i) and in
      wild-type animals. We also examined the effects of chronic treatment with the
      antidepressant drug fluoxetine in the same paradigm. MEASUREMENTS AND RESULTS: In
      both wild-type and GR-i mice, the 18-hour sleep deprivation or fluoxetine
      treatment had no effect on the spontaneous firing of 5-HT neurons recorded under
      anesthesia. However, sleep deprivation decreased the potency of the 5-HT1A
      agonist 8-OH-DPAT to inhibit 5-HT neuronal firing in wild-type mice, whereas it
      had no effect in GR-i animals. Conversely, after chronic fluoxetine treatment,
      the induced reduction of this 5-HT1A autoreceptor-driven response was of larger
      amplitude in GR-i than in wild-type mice. CONCLUSIONS: These data suggest that
      glucocorticoid-receptor activation by corticosterone participates in the
      antidepressant-like adaptive changes in 5-HT1A autoreceptors in sleep-deprived
      mice. On the other hand, GR-i animals exhibited enhanced 5-HT1A autoreceptor
      desensitization induced by fluoxetine, in line with data in other animal models
      of depression.

PMID- 16453980
TI  - Laboratory and field studies of naps and caffeine as practical countermeasures
      for sleep-wake problems associated with night work.
AB  - STUDY OBJECTIVES: To evaluate the effects of napping, caffeine, and napping plus
      caffeine on performance and alertness in both laboratory and field settings.
      DESIGN: (1) Laboratory Study: parallel-groups design with random assignment to 1
      of 4 experimental conditions. (2) Field Study: crossover design. SETTING: Sleep
      laboratory and field settings. PARTICIPANTS: (1) Laboratory Study: 68 healthy
      individuals; (2) Field Study: 53 shiftworkers who worked nights or rotating
      shifts. INTERVENTIONS: (1) Laboratory Study: an evening nap opportunity before
      the first 2 of 4 consecutive simulated night shifts plus placebo taken all 4
      nights, caffeine taken nightly, the combination of the nap and caffeine
      conditions, or placebo. (2) Field Study: an evening nap on the first 2 of 4
      consecutive night shifts plus caffeine taken nightly versus placebo taken nightly
      without naps. MEASUREMENTS AND RESULTS: (1) Laboratory Study: Napping, caffeine,
      and their combination all improved alertness and performance as measured by
      Maintenance of Wakefulness Test and Psychomotor Vigilance Task, but the
      combination of napping and caffeine was best in improving alertness. (2) Field
      Study: Napping plus caffeine improved performance as measured by Psychomotor
      Vigilance Test and decreased subjective sleepiness in individuals working the
      night shift. CONCLUSIONS: Napping plus caffeine helps improve performance and
      alertness of night-shift workers.

PMID- 16453981
TI  - Age-related changes in the time course of vigilant attention during 40 hours
      without sleep in men.
AB  - STUDY OBJECTIVES: To examine whether vigilant attention and sleepiness develop
      differently during prolonged wakefulness in young and older men. DESIGN, SETTING,
      AND PARTICIPANTS: Psychomotor vigilance task (PVT) performance and subjective
      sleepiness were determined in 14 sessions at 3 hour intervals in healthy young (n
      = 12, mean age: 25.2 years, range: 21-31 years) and older (n = 11, mean age: 66.4
      years, range: 61-70 years) men who were kept awake for 40 hours under continuous
      supervision in a sleep laboratory and on the morning after the recovery night.
      MEASUREMENTS AND RESULTS: PVT speed, response lapses and performance variability,
      and subjective sleepiness were analyzed. Sleep deprivation led to reversal of an
      age-related difference in PVT speed at the circadian trough of performance on the
      morning of the second day of prolonged wakefulness (Session x Age interaction: P
      < .0006). Beginning after 22 hours of wakefulness, the young men also produced
      more lapses (P < .004), showed higher performance instability (P < .0001), and
      felt sleepier (P < .03) than older men, especially during the morning after the
      night without sleep. CONCLUSIONS: Vigilant attention is more impaired after 1
      night without sleep in young men than in older men, which has important
      implications for the prevention of accidents associated with the loss of sleep.

PMID- 16453982
TI  - Effects of partial sleep deprivation on within-format and cross-format priming.
AB  - STUDY OBJECTIVES: The purpose of this study was to examine the effects of sleep
      on long-term priming. We report the results of a preliminary experiment that
      enabled us to verify that priming can last for 4 hours, and we also report the
      results of a study of partial sleep-deprivation. DESIGN: Subjects performed 2
      tasks: within-format and cross-format priming. SETTINGS: Sleep laboratory.
      PARTICIPANTS: Ninety-eight healthy young subjects participated in the 2 studies
      reported here: 48 in the preliminary experiment and 50 in the sleep-deprivation
      study. INTERVENTION: Testing after a 4-hour diurnal retention interval
      (Experiment 1) or after an equivalent interval filled with early or late sleep,
      or corresponding periods of wakefulness (Experiment 2). MEASUREMENTS AND RESULTS:
      A tachistoscopic identification paradigm, consisting of naming aloud briefly
      flashed drawings, was used to assess 2 priming conditions: a same-format or
      within-format condition (in which items were drawings in the study and test
      phases) and a different- or cross-format condition (in which the symbolic format
      of the items differed between the 2 phases: words/drawings). In Experiment 1, we
      revealed significant priming effects in both conditions after a 4-hour interval.
      In Experiment 2, only same-format priming effects were observed, but their
      magnitude was smaller than in Experiment 1. There was no significant difference
      in priming scores between the sleep and wake groups. CONCLUSIONS: Sleep does not
      appear to have a strong effect on priming. Instead, priming appears to be
      affected by circadian influences.

PMID- 16453983
TI  - Sleep deprivation in rats produces attentional impairments on a 5-choice serial
      reaction time task.
AB  - STUDY OBJECTIVES: To develop a rodent model of the attentional dysfunction caused
      by sleep loss. DESIGN: The attentional performance of rats was assessed after 4,
      7, and 10 hours of total sleep deprivation on a 5-choice serial reaction time
      task, in which rats detect and respond to brief visual stimuli. SETTING: The rats
      were housed, sleep deprived, and behaviorally tested in a controlled laboratory
      setting. PARTICIPANTS: Ten male Long-Evans rats were used in the study.
      INTERVENTIONS: Rats were trained to criteria and subsequently tested in daily
      sessions of 100 trials at approximately 4:00 PM (lights on 8:00 AM-8:00 PM).
      Attentional performance was measured after 4, 7, 10 hours of total sleep
      deprivation induced by gentle handling. RESULTS: Sleep deprivation produced a
      monotonic increase in response latencies across the 4-hour, 7-hour, and 10-hour
      deprivations. Sleep deprivation also led to increased omission errors, but the
      overall number of perseverative and premature responses was unchanged. Subgroups
      of rats were differentially affected in the number of omission errors and
      perseverative responses. CONCLUSIONS: The effects of sleep deprivation on rats
      are compatible with a range of human findings on the effects of sleepiness on
      selective attention, psychomotor vigilance, and behavioral control. Rats also
      exhibited differential susceptibility to the effects of sleep deprivation,
      consistent with 'trait-like' susceptibility that has been found in humans. These
      findings indicate the feasibility of using the 5-choice serial reaction time task
      as an animal model for investigating the direct links between homeostatic sleep
      mechanisms and resulting attentional impairments within a single animal subject.

PMID- 16453984
TI  - Hypersynchronous delta waves and somnambulism: brain topography and effect of
      sleep deprivation.
AB  - STUDY OBJECTIVES: Hypersynchronous delta activity (HSD) is usually described as
      several continuous high-voltage delta waves (> or = 150 microV) in the sleep
      electroencephalogram of somnambulistic patients. However, studies have yielded
      varied and contradictory results. The goal of the present study was to evaluate
      HSD over different electroencephalographic derivations during the non-rapid eye
      movement (NREM) sleep of somnambulistic patients and controls during normal sleep
      and following 38 hours of sleep deprivation, as well as prior to sleepwalking
      episodes. DESIGN: N/A. SETTING: Sleep disorders clinic. PATIENTS: Ten adult
      sleepwalkers and 10 sex- and age-matched control subjects were investigated
      polysomnographically during a baseline night and following 38 hours of sleep
      deprivation. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: During normal sleep,
      sleepwalkers had a significantly higher ratio of HSD over the time spent in stage
      2, 3 and 4 on frontal and central derivations when compared with controls. Sleep
      deprivation resulted in a significant increase in the ratio of the time in HSD
      over the time in stage 4 on the frontal lead in both groups and on the central
      lead in controls. There was no evidence for a temporal accumulation of HSD prior
      to the episodes. CONCLUSIONS: HSD shows a clear frontocentral gradient across all
      subjects during both baseline and recovery sleep and has relatively low
      specificity for the diagnosis of NREM parasomnias. Increases in HSD after sleep
      deprivation may reflect an enhancement of the homeostatic process underlying
      sleep regulation.

PMID- 16453985
TI  - Sex differences in insomnia: a meta-analysis.
AB  - STUDY OBJECTIVE: Most but not all epidemiologic evidence suggests a female
      predisposition of insomnia. We applied meta-analytic methods to investigate sex
      differences in the risk of insomnia among the published epidemiologic studies.
      DESIGN: Meta-analysis with Comprehensive Meta-Analysis (Englewood, NJ); 9
      different analyses were performed to investigate the sex difference of insomnia
      among different conditions. SETTING: A comprehensive search of the medical
      literature databases was performed to identify epidemiologic studies of insomnia.
      A rolling snowball method was also used. PARTICIPANTS: General population.
      INTERVENTIONS: N/A. RESULT: Thirty-one related papers were found, but 2 studies
      only reported the subtype prevalence of insomnia. All other studies (1,265,015
      participants, female/male: 718,828/546,187) were included in the overall analysis
      of insomnia. A risk ratio of 1.41 [95% confidence interval: 1.28-1.55] for female
      versus male was found. The female excess in the risk of insomnia in large and
      quality studies was much higher than that of small and nonquality studies. The
      trend of female predisposition was consistent and progressive across age, with
      more significance in the elderly. The use of various criteria and frequency and
      duration of insomnia did not influence the predisposition of female in the risk
      of developing insomnia. Although obvious female excess in the risk of insomnia
      exists among different regions, there was a relatively lower female excess in
      East Asia. CONCLUSION: This meta-analysis confirmed a female predisposition of
      insomnia. Further studies will be needed to examine the roles of different
      factors in leading to the sex difference of insomnia.

PMID- 16453987
TI  - Relative treatment rates for sleep disorders and sleep disturbances following
      abortion and childbirth: a prospective record-based study.
AB  - Sleep disorders are linked with mood disorders and other psychiatric illnesses.
      Many women attribute sleep difficulties to abortion, but this self-diagnosis has
      not been tested using record-based evidence. Examination of records for 56,824
      women with no known history of sleep disorders or sleep disturbances revealed
      that women were more likely to be treated for sleep disorders or disturbances
      following an induced abortion compared to a birth. The difference was most
      pronounced in the first 180 days after pregnancy resolution and was not
      significant after the third year.

PMID- 16453986
TI  - The determinants of the apnea threshold during NREM sleep in normal subjects.
AB  - STUDY OBJECTIVE: To determine whether (1) postmenopausal women have a higher
      apnea threshold than premenopausal women and men and (2) hormone replacement
      therapy would decrease the apnea threshold in postmenopausal women. DESIGN:
      Protocol #1: Analysis of a prospectively collected database of 55 subjects who
      had undergone an apnea-threshold protocol. Protocol #2: Intervention study: apnea
      threshold compared in 6 postmenopausal women before and after 30 days of
      replacement therapy with progestin and estrogen. SETTING: Research sleep
      laboratory. PARTICIPANTS: Healthy volunteers aged 18 to 65 years without evidence
      of sleep-disordered breathing. INTERVENTIONS: Hypocapnia was induced via nasal
      mechanical ventilation for 3 minutes during stable non-rapid eye movement sleep.
      Cessation of mechanical ventilation resulted in hypocapnic central apnea or
      hypopnea, depending upon the magnitude of the hypocapnia. The change in endtidal
      CO2 at the apnea threshold was defined as the change in end-tidal CO2 associated
      with the apnea closest to the last hypopnea. MEASUREMENTS AND RESULTS: The change
      in the end-tidal CO2 at the apnea threshold was highest in the premenopausal
      women (4.6+/-0.6 mm Hg), with no difference between the postmenopausal women
      (3.1+/-0.5 mm Hg) and men (3.4+/-0.7 mm Hg). Determinants of the change in
      endtidal CO2 at the apnea threshold included sex and menopause status. Hormone
      replacement therapy increased the change in end-tidal CO2 at the apnea threshold
      from 2.9+/-0.4 mm Hg to 4.8+/-0.4 mm Hg (P<.001). CONCLUSIONS: These data support
      the hypothesis that estrogens and progestins positively influence the apnea
      threshold and control of breathing during non-rapid eye movement sleep.

PMID- 16453988
TI  - Daytime sleepiness and the COMT val158met polymorphism in patients with Parkinson
      disease.
AB  - STUDY OBJECTIVE: A preliminary study by our group suggested an association
      between daytime sleepiness and the catechol-O-methyltransferase (COMT) val158met
      polymorphism (rs4680) in patients with Parkinson disease (PD). We sought to
      confirm this association in a large group of patients with PD. DESIGN: Genetic
      association study in patients with PD. SETTING: Movement disorder sections at 2
      university hospitals. PARTICIPANTS: PD patients with and without episodes of
      suddenly falling asleep matched for antiparkinsonian medication, disease
      duration, sex, and age, who participated in a previous genetic study on dopamine
      receptor polymorphisms. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS:
      In this study, 240 patients with PD (154 men; age 65.1 +/- 6.1 years; disease
      duration 9.4 +/- 6.0 years) were included. Seventy had the met-met (LL), 116 the
      met-val (LH), and 54 the val-val (HH) genotype. In the combined LL+LH group
      (featuring reduced COMT activity), the mean Epworth Sleepiness Scale (ESS) score
      was 9.0 +/- 5.9 versus 11.0 +/- 6.1 in the HH (high COMT activity) group (P =
      .047). Forty-seven percent of the LL and LH patients had sudden sleep onset
      compared with 61% of the HH patients (P = .07). Logistic regression, however,
      showed that both pathologic ESS scores (i.e., > 10) and sudden sleep onset were
      predicted by subjective disease severity (P < .001 each) but not by the COMT
      genotype. CONCLUSIONS: Our previous finding that the L-allele may be associated
      with daytime sleepiness could not be confirmed in the present study. Altogether,
      our data do not support a clinically relevant effect of the COMT genotype on
      daytime sleepiness in PD.

PMID- 16453989
TI  - Validation of a 3-factor scoring model for the Pittsburgh sleep quality index in
      older adults.
AB  - STUDY OBJECTIVES: The Pittsburgh Sleep Quality Index (PSQI) is widely used to
      assess subjective sleep disturbances in psychiatric, medical, and healthy adult
      and older adult populations. Yet, validation of the PSQI single-factor scoring
      has not been carried out. DESIGN: The PSQI was administered as a self-report
      questionnaire. Using a cross-validation approach, scores from the PSQI were
      analyzed with exploratory and confirmatory factor analyses. SETTING: San Diego,
      Denver, and Los Angeles community-based clinics. PARTICIPANTS: Community-dwelling
      depressed and nondepressed adults older that 60 years of age (N = 417)
      MEASUREMENTS AND RESULTS: Results yielded a 3-factor scoring model that obtained
      a measure of perfect fit and was significantly better fitted than either the
      original single-factor model or a 2-factor model. Components of the 3 factors
      were characterized by the descriptors sleep efficiency, perceived sleep quality,
      and daily disturbances. CONCLUSIONS: These findings validate the factor structure
      of the PSQI and demonstrate that a 3-factor score should be used to assess
      disturbances in three separate factors of subjective sleep reports.

PMID- 16453990
TI  - Is the employer-based health coverage system a foundation or a relic?

PMID- 16453991
TI  - A new life for Medicare HMOs?

PMID- 16453992
TI  - Screening and treatment of hypercholesterolemia for prevention of coronary heart
      disease.
AB  - Undertreatment of hypercholesterolemia for secondary prevention of coronary heart
      disease has been widely documented. Less is known about screening and treatment
      for primary prevention. To evaluate recent trends, the rates of low-density
      lipoprotein (LDL) cholesterol screening and treatment for primary and secondary
      prevention of coronary heart disease in 1999 and 2003 were quantified from the
      National Disease and Therapeutic Index and compared. Data were used to examine
      LDL level reporting, rates at which target levels were attained, and drug therapy
      among National Cholesterol and Education Panel (NCEP) risk groups. The rate of
      LDL level reporting increased with greater NCEP risk, ranging from 6% to 7% for
      visits without risk factors to 31% to 42% for secondary prevention. Rates of
      meeting LDL targets decreased with greater NCEP risk, ranging from 87% to 88% for
      visits without risk factors to 29% to 43% for secondary prevention. Drug therapy
      recommendation also decreasedwith greater NCEP risk. Despite improvements,
      underscreening and undertreatment of hypercholesterolemia persists in outpatient
      visits.

PMID- 16453993
TI  - Home ultraviolet B phototherapy: a cost-effective option for severe psoriasis.
AB  - The cost of treating severe psoriasis has risen dramatically, and treatment
      options vary widely in terms of cost and efficacy. However, little information is
      available on the relative costs of home phototherapy and other long-term
      management options, specifically in the context of managed care. A payer
      perspective cost model was developed to estimate and compare the direct
      expenditures associated with a 30-year course of various treatments for severe
      psoriasis. Within two years of treatment initiation, home-administered
      ultraviolet B phototherapy was less costly than any of the other treatments
      examined, including methotrexate, psoralen plus ultraviolet A, the retinoid
      acitretin, and new biologic agents. In addition, the efficacy and safety profile
      of home ultraviolet B phototherapy make it an excellent choice for extended
      management.

PMID- 16453994
TI  - Evolution of managed care pharmacy and therapeutics committees.

PMID- 16453995
TI  - The evolutionary role of the pharmacy and therapeutics committee in technology
      assessment.
AB  - The origins of the Pharmacy and Therapeutics (P&T) Committee is intertwined with
      the evolution of the modern practice of pharmacy. Although the P&T Committee has
      been uniquely developed to help make coverage decisions, this implies that its
      technology assessment function, particularly with regard to medicines, has paved
      the way to more cost-effective and evidence-based practice. This article, which
      briefly traces the lineage of the first known "formulary" employed during the
      Revolutionary War to today's P&T Committee, argues that its true function-
      technology assessment--serves as the basis for coverage decisions throughout
      health systems.

PMID- 16453996
TI  - Hurricanes may help the move toward portable medical data.

PMID- 16453997
TI  - Medicare part D confusion.

PMID- 16454001
TI  - [Role of rehabilitation in the management of urinary incontinence in women].

PMID- 16454002
TI  - [Skin preparation in surgical patients: the golden rules].

PMID- 16454003
TI  - [Practicing in a prison milieu].

PMID- 16454004
TI  - [Masks in the hospital milieu].

PMID- 16454005
TI  - [Continued improvement in blood transfusion safety].

PMID- 16454006
TI  - [Infusion pumps].

PMID- 16454007
TI  - [Nursing personnel security: emergency communication equipment].

PMID- 16454008
TI  - [L-polylactic acid].

PMID- 16454009
TI  - Relationships of Indoor, Outdoor, and Personal Air (RIOPA). Part I. Collection
      methods and descriptive analyses.
AB  - This study on the relationships of indoor, outdoor, and personal air (RIOPA) was
      undertaken to collect data for use in evaluating the contribution of outdoor
      sources of air toxics and particulate matter (PM) to personal exposure. The study
      was not designed to obtain a population-based sample, but rather to provide
      matched indoor, outdoor, and personal concentrations in homes that varied in
      their proximity to outdoor pollution sources and had a wide range of air exchange
      rates (AERs). This design allowed examination of relations among indoor, outdoor,
      and personal concentrations of air toxics and PM across a wide range of
      environmental conditions; the resulting data set obtained for a wide range of
      environmental pollutants and AERs can be used to evaluate exposure models.
      Approximately 100 households with residents who do not smoke participated in each
      of three cities in distinct locations expected to have different climates and
      housing characteristics: Elizabeth, New Jersey; Houston, Texas; and Los Angeles
      County, California. Questionnaires were administered to characterize homes,
      neighborhoods, and personal activities that might affect exposures. The
      concentrations of a suite of volatile organic compounds (VOCs) and carbonyl
      compounds, as well as the fraction of airborne particulate matter with a mass
      median aerodynamic diameter < or = 2.5 microm (PM2.5), were measured during
      continuous 48-hour sessions in which indoor, outdoor, and personal air samples
      were collected simultaneously. During the same 48-hour period, the AER
      (exchanges/hr; x hr(-1)) was determined in each home, and carbonyl compounds were
      measured inside vehicle cabins driven by a subset of the participants. In most of
      the homes, measurements were made twice, during two different seasons, to obtain
      a wide distribution of AERs. This report presents in detail the data collection
      methods, quality control measures, and initial analyses of data distributions and
      relations among indoor, outdoor, and personal concentrations. The results show
      that indoor sources dominated personal and indoor air concentrations of many
      measured VOCs and carbonyl compounds. For several measured species, personal
      concentrations were higher than either indoor or outdoor concentrations,
      indicating the presence of some sources closely related to personal activities.
      For some species there were no significant indoor sources in the majority of the
      homes; thus indoor concentrations were mainly determined by outdoor
      concentrations in these homes. The range of distributions of air concentrations
      for the measured VOCs, formaldehyde and acetaldehyde, PM2.5, and AERs were
      generally consistent with values reported previously in the literature. Thus
      associations derived from or models based on this data set that may link the
      influence of outdoor sources with indoor air concentrations of air toxics and
      PM2.5 can be relevant to other urban settings. The simultaneous measurements of
      indoor concentrations, outdoor concentrations, AERs, and room volumes allowed the
      use of a mass balance model, under the steady-state approximation, to
      mechanistically examine the relative contributions of indoor and outdoor sources
      to measured indoor concentrations on a home-by-home basis. Estimated indoor
      source strengths for VOCs and carbonyl compounds varied widely from home to home,
      consistent with the indoor-outdoor concentration patterns, as shown in scatter
      plots. The indoor source estimations agreed with published values for PM2.5 and
      with the general understanding of sources of VOCs and carbonyl compounds. The
      source strengths reported here, derived from hundreds of homes, are an important
      contribution to the literature on exposure to air toxics. For the first time for
      many compounds, these estimates present a cohesive set of measurements across a
      range of air toxics in paired indoor, outdoor, and personal samples along with
      AER and questionnaire results that can be used for future analyses of indoor air
      quality. The estimation of outdoor contributions to measured indoor
      concentrations provides insights about the relative importance of indoor and
      outdoor sources in determining indoor concentrations, the main determinant of
      personal exposure for most of the measured compounds. In this report simple
      statistical tests mainly of the pooled data were used to analyze differences by
      sampling site, emission source type, season, home type, and home age. Paired
      adult-child personal concentrations within the same home were also compared using
      the pooled data set. These analyses generated some intriguing results that
      warrant more in-depth investigation in the future.

PMID- 16454010
TI  - Diagnosis and treatment of acute periodontal conditions.

PMID- 16454011
TI  - The periodontal prosthesis mode of transition to an implant-supported dentition.
AB  - In recent years, implant-supported reconstructions have become a welcome
      alternative to dentures for those who have lost their natural dentition. While
      the benefits of the final implant-supported reconstruction may be obvious, the
      planning and execution of therapy to achieve this result may be bewildering to
      many dentists. Four main modes of transfer have evolved: an uncontrolled or
      "haphazard" transition; the traditional "dentures first" mode, an immediate
      transition, and a staged transition. This article proposes an additional mode of
      transition called periodontal prosthesis, which has the potential to make the
      transition process smoother and more predictable while providing optimal
      retention of alveolar supporting structures and generating optimal esthetics.

PMID- 16454012
TI  - Localized periodontitis as a long-term effect of oral piercing: a case report.
AB  - Recent years have seen a dramatic increase in the number of published articles on
      short-term complications of oral piercing, possibly reflecting an increase in the
      popularity of this practice. Long-term effects of oral piercing, however, have
      had minimal documentation. This case report of a 28-year-old woman with piercing
      of the tongue and lower lip demonstrated localized severe periodontitis as a
      destructive long-term outcome related to oral piercing. The patient reported that
      she had worn 2 tongue rings and a mandibular labrette (lip piercing) in the form
      of a bar for 12 years. Plaque and calculus accumulation, severe inflammation,
      tooth mobility, severe horizontal radiographic bone loss, and deep pocketing were
      observed in teeth affected by the jewelry.

PMID- 16454013
TI  - Biological and clinical rationale for early implant loading.
AB  - This article questions whether early implant loading always leads to
      pseudointegration, as postulated by Branemark's original protocol, or whether the
      waiting period of 3 to 6 months can be significantly shortened in specific
      clinical situations and refined surgical protocols. The rationale for immediate
      loading of dental implants is discussed, and the evidence that immediate loading
      leads to implant fibrous encapsulation is reviewed. This evidence is opposed by
      conflicting indications that early loading induces bone growth. Micro- and
      macromovement are defined, and their role, as well as the importance of implant
      surface in the early loading protocol, is discussed. Recently published landmark
      human clinical trials on early implant loading also are reviewed, along with
      clinical, surgical, and prosthetic tips to take into consideration when planning
      an early implant loading case.

PMID- 16454014
TI  - Evaluation of allogeneic bone graft substitute for treatment of periodontal
      osseous defects: 6-month clinical results.
AB  - This article is an initial clinical evaluation of the use of Puros, a specially
      processed allogeneic bone graft substitute, for treatment of periodontal osseous
      defects. Nine patients with chronic periodontitis contributed 1 osseous defect
      each. Clinical and surgical measurements were taken at the time of the initial
      grafting and 6 months later at the time of a surgical re-entry. On average,
      probing depth improved by 3 mm, and there was 2.5 mm bone fill. Resorption of the
      alveolar crest was minimal. All cases healed satisfactorily, and at the time of
      re-entry only 1 case required re-treatment. Puros appears to be a useful and
      beneficial material for the treatment of proximal type human periodontal defects.

PMID- 16454015
TI  - Surface protection for newly erupting first molars.
AB  - The objective of this study was to compare the retention of GC Fuji Triage glass
      ionomer to Delton FS+, a resin-based sealant on saliva-contaminated enamel
      surfaces. Seventy-two extracted noncarious human permanent molars were divided
      into 3 groups for sealing using Triage (T), Delton FS+ with Prime & Bond NT (DP),
      and Delton FS+ (D) alone. After prophylaxis with pumice, Groups D and DP were
      etched with 38% H3PO4 for 30 seconds. Group T was treated with Cavity
      Conditioner. A single drop of natural saliva was applied to the occlusal surface
      with a microbrush. Sealants were then placed according to the manufacturer's
      directions. Bonding agent was applied and light-cured for 20 seconds before the
      application of Delton for the DP group. All sealants covered the entire occlusal
      surface. The groups were further subdivided into 3 time-evaluation intervals: 6
      months, 1 year, and 2 years (8 samples each). They were thermocycled (5 degrees C
      to 55 degrees C, 1 minute dwell time) at 250, 500, and 1,000 cycles,
      respectively. After each thermocycling period, they were subjected to toothbrush
      abrasion for their respective times (3,000 strokes, 6,000 strokes, and 12,000
      strokes). All samples were finally observed clinically for retention of sealant.
      Samples with clinically visible loss of material were further evaluated under a
      scanning electron microscope (SEM) to verify the loss in the pits and fissures.
      After the first thermocycling period, 5 of the 24 samples (21%) of Group D
      revealed complete visual loss of sealant. There was no further loss after the
      second period. After the third period of thermocycling, an additional 4 samples
      revealed complete visible loss of the sealant material from Group D (total 37.5%
      failure). SEM evaluation verified the complete loss of sealants. Groups T and DP
      showed 100% retention after the entire period of aging and toothbrush-abrasion.
      Both of these groups demonstrated similar wear rates. Therefore, concerning
      fluoride release and simpler technique, especially with newly-erupting molars,
      Triage has advantages.

PMID- 16454016
TI  - Clinical evaluation of chemical and light-activated tooth whitening systems.
AB  - Tooth whitening has become one of the most popular dental treatments available.
      This article compares the efficacy of 2 in-office whitening systems using a split
      arch, randomized, parallel, blinded clinical evaluation study. Both in-office
      tooth whitening systems were effective and there was no significant statistical
      difference over the 2-week period of observation. The use of light did not
      demonstrate any benefit over the chemically activated tooth whitening system
      after a 2-week recall.

PMID- 16454017
TI  - A better practice through vision and goals.

PMID- 16454018
TI  - [New discoveries about old age].

PMID- 16454019
TI  - [Well cared for and creative old age].

PMID- 16454020
TI  - [Still always the "second adolescence"].

PMID- 16454021
TI  - [More treatment options in acute diseases].

PMID- 16454022
TI  - [Difficult future for a particular group of people].

PMID- 16454023
TI  - ["Heroes" and "pirates" in child care].

PMID- 16454024
TI  - [Not only in joy and sorrow].

PMID- 16454025
TI  - [Sometimes things turn out differently from the expected].

PMID- 16454026
TI  - [Adrien and Moisette].

PMID- 16454027
TI  - [Aging: but it does not deserve comment].

PMID- 16454028
TI  - [Reconciling the logic of various people].

PMID- 16454029
TI  - [Joy in the professionalism of students].

PMID- 16454030
TI  - [When the philosophy of nursing creates a basis for liberalism].

PMID- 16454031
TI  - [What a mess, Mr. Blocher!].

PMID- 16454032
TI  - [Life changes. Until the end of life].

PMID- 16454033
TI  - [Sorrow-or merely the advent of old age?].

PMID- 16454034
TI  - [The importance of preventive medicine].

PMID- 16454035
TI  - [Care with important consequences].

PMID- 16454036
TI  - Whole-mount BrdU staining of proliferating cells by DNase treatment: application
      to postnatal mammalian retina.

PMID- 16454037
TI  - Whole embryo chromatin immunoprecipitation protocol for the in vivo study of
      zebrafish development.

PMID- 16454039
TI  - Ectopic transgene expression in butterfly imaginal wing discs using vaccinia
      virus.

PMID- 16454038
TI  - Nested multigene MSP/DHPLC method for analyzing promoter hypermethylation status
      in clinical samples.

PMID- 16454040
TI  - Concurrent mRNA and protein extraction from the same experimental sample using a
      commercially available column-based RNA preparation kit.

PMID- 16454041
TI  - Identification of new fluorescent protein fragments for bimolecular fluorescence
      complementation analysis under physiological conditions.
AB  - Protein-protein interactions play a pivotal role in coordinating many cellular
      processes. Determination of subcellular localization of interacting proteins and
      visualization of dynamic interactions in living cells are crucial to elucidate
      cellular functions of proteins. Using fluorescent proteins, we previously
      developed a bimolecular fluorescence complementation (BiFC) assay and a
      multicolor BiFC assay to visualize protein-protein interactions in living cells.
      However, the sensitivity of chromophore maturation of enhanced yellow fluorescent
      protein (YFP) to higher temperatures requires preincubation at lower temperatures
      prior to visualizing the BiFC signal. This could potentially limit their
      applications for the study of many signaling molecules. Here we report the
      identification of new fluorescent protein fragments derived from Venus and
      Cerulean for BiFC and multicolor BiFC assays under physiological culture
      conditions. More importantly, the newly identified combinations exhibit a 13-fold
      higher BiFC efficiency than originally identified fragments derived from YFP.
      Furthermore, the use of new combinations reduces the amount of plasmid required
      for transfection and shortens the incubation time, leading to a 2-fold increase
      in specific BiFC signals. These newly identified fluorescent protein fragments
      will facilitate the study of protein-protein interactions in living cells and
      whole animals under physiological conditions.

PMID- 16454042
TI  - PCR-based tandem epitope tagging system for Escherichia coli genome engineering.
AB  - Biological discovery in the postgenomic era requires a systematic and high
      throughput experimental approach. To this end, a versatile PCR-based tandem
      epitope tagging system is described, which inserts a tandem epitope coding
      sequence into any desired position of the Escherichia coli chromosome. Template
      plasmids were constructed that carry tandem copies of the epitope encoding
      sequence, Flp recombinase target (FRT) sites, and antibiotic resistance genes.
      The linear DNA fragment, amplified from the template plasmid with extensions
      homologous to the end of the target gene and part of its downstream region, was
      transformed into E. coli K-12 MG1655 harboring the bacteriophage gamma Red
      recombination system. The antibiotic resistance gene was then removed from the
      inserted heterologous PCR fragment using Flp recombinase. This epitope tagging
      system was applied to global transcription factors of E. coli to obtain proteins
      fused with tandem c-myc epitope tags. The tandem myc epitope-fused transcription
      factors were successfully detected by Western blot analysis and chromatin
      immunoprecipitation with increased detection sensitivity and higher yield. Higher
      copy numbers of the epitope molecule allowed the use of more stringent
      experimental conditions to increase the signal-to-noise ratio in subsequent
      experimental applications. Furthermore, judging from the measurement of gene
      expression using reverse transcription PCR (RT-PCR), the epitope-fused
      transcription factors retained their normal function for gene regulation in vivo.

PMID- 16454043
TI  - System of centromeric, episomal, and integrative vectors based on drug resistance
      markers for Saccharomyces cerevisiae.
AB  - Integrative, centromeric, and episomal plasmids are essential for easy, fast, and
      reliable genetic manipulation of yeast. We constructed a system of shuttle
      vectors based on the widely used plasmids of the pRS series. We used genes
      conferring resistance to Geneticin (kanMX4), nourseothricin (natNT2), and
      hygromycin B (hphNT1) as markers. The centromeric and episomal plasmids that we
      constructed can be used the same way as the traditional auxotrophic marker-based
      shuttle vectors (pRS41x and pRS42x series). Additionally, we created a set of
      nine yeast integrative vectors with the three dominant markers. These plasmids
      allow for direct integration in the LEU2, URA3, and HIS3 locus of any yeast
      strain and the concomitant partial deletion of the gene. This prevents multiple
      integrations and allows for the rapid identification of correct integrants. The
      set of new vectors considerably enhances the flexibility of genetic manipulations
      and gene expression in yeast. Most notably, the new vectors allow one to work
      with natural yeast isolates, which do not contain auxotrophic markers.

PMID- 16454044
TI  - Highly efficient yeast-based in vivo DNA cloning of multiple DNA fragments and
      the simultaneous construction of yeast/ Escherichia coli shuttle vectors.
AB  - In vivo recombinational cloning in yeast is a very efficient method. Until now,
      this method has been limited to experiments with yeast vectors because most
      animal, insect, and bacterial vectors lack yeast replication origins. We
      developed a new system to apply yeast-based in vivo cloning to vectors lacking
      yeast replication origins. Many cloning vectors are derived from the plasmid
      pBR322 and have a similar backbone that contains the ampicillin resistance gene
      and pBR322-derived replication origin for Escherichia coli. We constructed a
      helper plasmid pSUO that allows the in vivo conversion of a pBR322-derived vector
      to a yeast/E. coli shuttle vector through the use of this backbone sequence. The
      DNA fragment to be cloned is PCR-amplified with the addition of 40 bp of homology
      to a pBR322-derived vector. Cotransformation of linearized pSU0, the pBR322
      derived vector, and a PCR-amplified DNA fragment, results in the conversion of
      the pBR322-derived vector into a yeast/E. coli shuttle vector carrying the DNA
      fragment of interest. Furthermore, this method is applicable to multifragment
      cloning, which is useful for the creation of fusion genes. Our method provides an
      alternative to traditional cloning methods.

PMID- 16454045
TI  - High-throughput multi-antigen microfluidic fluorescence immunoassays.
AB  - Here we describe the development of a high-throughput multi-antigen microfluidic
      fluorescence immunoassay system. A 100-chamber polydimethylsiloxane (PDMS) chip
      performs up to 5 tests for each of 10 samples. In this particular study system,
      the specificity of detection was demonstrated, and calibration curves were
      produced for C-reactive protein (CRP), prostate-specific antigen (PSA), ferritin,
      and vascular endothelial growth factor (VEGF). The measurements show sensitivity
      at and below clinically normal levels (with a signal-to-noise ratio >8 at as low
      as 10 pM antigen concentration). The chip uses 100 nL per sample for all tests.
      The developed system is an important step toward derivative immunoassay
      applications in scientific research and "point-of-care" testing in medicine.

PMID- 16454048
TI  - [Anemia and deficiency of vitamin A in children evaluated in a nutritional
      attention center from Caracas].
AB  - In order to determine the prevalence of anemia and the deficiency of vitamin A in
      children under 10 years, the concentration of hemoglobin, transferrin saturation,
      serum iron and the nutritional state of vitamin A were studied between 1999 and
      2000, in 124 children with moderate malnutrition and 98 healthy children who
      attend triage consultation in the Centro de Atencion Nutricional Infantil
      Antimano (CANIA, Caracas) by means of plasma retinol test (high performance
      liquid chromatography), relative dose response test (RDR) and conjunctival
      impression cytology (CIC). The dietary intake was analyzed by 24 hour recall. The
      Student t and Chi-square test were used for the statistical analysis of the data.
      The prevalence of vitamin A deficiency was approximately 10% in malnourished and
      healthy children, the CIC test discriminated a proportion of vitamin A deficient
      children superior to 25% and RDR test detected a significantly smaller percentage
      of deficiency in healthy children (p < 0.05). The prevalence of anemia was
      significantly higher in malnourished (34.2%) than in healthy children (19.2%). In
      children under 2 years the percentage of anemia reached 75.8% in undernourished
      children and 50% in healthy children. The consumption of macronutrients and
      micronutrients was inadequate; more than 40% undernourished children had caloric
      and macronutrients intake adequacy below 85%, whereas this level of adequacy in
      healthy children was around 30%. These results indicate there were problems of
      moderate anemia and moderate vitamin A deficiency in the studied infantile
      population, without significant differences between moderate undernourished and
      healthy children.

PMID- 16454046
TI  - T-cell line for HIV drug screening using EGFP as a quantitative marker of HIV-1
      replication.
AB  - The rapid increase of viral strains that are resistant to the currently available
      antiretroviral drugs is a threat to the success of current human immunodeficiency
      virus type 1 (HIV-1) treatment and emphasizes the importance of developing novel
      anti-HIV-1 compounds. To improve the current abilities to screen for novel HIV-1
      inhibitors, here we introduce a T-cell-based reporter cell line (JLTRG-RS) that
      expresses both HIV-1 coreceptors, CXCR4 and CCRS, and provides the convenience of
      using enhanced green fluorescent protein (EGFP) as a direct and quantitative
      marker. Unlike previous EGFP-based reporter cell lines, JLTRG-RS cells have an
      unusually high dynamic signal range, sufficient for plate reader detection using
      a 384-well format. In this format, JLTRG-R5 cell-based infectivity assays have a
      Z'-factor of 0.78, which defines the assay as extremely robust and clearly
      amenable to high-throughput screening. The functional similarity of the JLTRG-R5
      cell line and peripheral blood mononuclear cells (PBMCs) was demonstrated through
      the identity of the inhibitory concentrations, 50% (IC50s) for four
      antiretroviral compounds or neutralizing antibodies. Because EGFP can be directly
      and continuously quantified in cell culture, the reporter cell line requires no
      manipulation during assay preparation or analysis. In addition, the EGFP marker
      allows for data acquisition at an optimal time point by prescreening selected
      positive control wells using fluorescent microscopy. These characteristics make
      the system extremely flexible, rapid, and inexpensive. Due to its intrinsic
      flexibility, the JLTRG-R5 cell-based reporter system provides a powerful tool to
      greatly facilitate future screening for HIV-1 inhibitors.

PMID- 16454047
TI  - [Study of nutritional factors related to breast cancer prevention. Importance of
      animal models approaches].
AB  - Breast cancer is the most common worldwide neoplasia in women. The totality of
      etiology factors of breast cancer is unknown and thus an effective preventive
      strategy has not been developed. Risk factors associated to breast cancer can be
      grouped into three broad categories: a) family history (hereditary) factors, b)
      endocrine and reproductive factors and c) environmental and life-style factors
      including diet. Animal models of chemical induced mammary carcinogenesis with 7,
      12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea have been useful in the
      study of biology, treatment and prevention of breast cancer. In this review we
      show the usefulness and advantages of animal models in the study of nutritional
      factors associated with breast cancer in order to propose new prevention
      strategies. We review briefly different experimental approaches as well as some
      physiologic effects and mechanisms of some nutritional factors studied with
      animal models of mammary carcinogenesis. Nutritional factors reviewed were: a)
      energy restriction and high-fat intake, b) soy and phytoestrogens, c) retinoids
      and carotenoids, d) conjugated linoleic acid, and e) brown seaweed and iodine.

PMID- 16454049
TI  - [Behavior of serum zinc levels during pregnancy].
AB  - The zinc intervenes in the growth and development, being of vital importance in
      the pregnancy. In order to determine the behavior of the serum zinc levels during
      the pregnancy associating it to the anthropometric nutritional status and dietary
      intake, 108 pregnants were assessed longitudinally, between March 1998 and
      December 1999, in the 12, 22 and 33 week pregnancy. Anthropometric parameters,
      serum zinc and albumin, and dietary intake of energy, proteins, zinc and fiber
      were determined. Descriptive standards and frequencies were calculated and
      Student's t test, Wilcoxon signed rank test, one-way analysis of variance and
      Pearson correlation test were made. Significant decrease of the serum zinc and
      albumin was observed during the gestation. The serum zinc levels in the first
      trimester differed significantly according to intake of oligoelement. In the
      second trimester, zinc concentrations differed significantly according to
      maternal age and weight gain, while no significant differences were found by
      parity, pregestational body mass index, height-for-age in none of the trimesters.
      Changes in the serum zinc concentrations are confirmed throughout the pregnancy,
      these modifications are explained partially by the decrease of serum albumin.
      Serum levels of zinc during gestation do not depend of parity or pregestational
      anthropometric nutritional status.

PMID- 16454050
TI  - [Soluble transferrin receptor-like indicator of iron nutritional status in
      Venezuelan preschoolers].
AB  - Soluble transferrin receptor (sTfR) is an effective tool for iron deficiency (ID)
      diagnosis, and unlike serum ferritin (SF) and others indicators, is not affected
      by acute phase response during inflammatory processes. In order to diagnose ID
      using sTfR as iron status indicator and to estimate its utility, a cross
      sectional, descriptive study was performed in 190 preschoolers of Valencia,
      Venezuela. sTfR and SF were assessed by enzimoimmunoassay; hemoglobin (Hb) by
      automated method, and parasitic infestation by stool examination. ID was defined
      as SF < 12 micro/L, iron deficient erythropoiesis as sTfR > 2.3 mg/L, and anemia
      as Hb < 11.0 g/dL and < 11.5 g/dL, according to age. Statistical analysis
      included descriptives, frequency distribution, chi2 and Spearman correlations. ID
      was highly prevalent as shown by serum ferritin (69.0%), sTfR (72.5%) and sTfR/FS
      ratio (81.9%). sTfR/FS ratio was more efficient in the ID diagnosis than any
      other indicator by itself. A high percentage of anemia was found (25.9%), from
      which, 79.5% was due to iron deficiency. No association to parasites was
      observed. It is concluded that sTfR is a useful tool for the diagnosis of iron
      deficiency and that a high nutritional risk for iron nutritional status. Low
      intake of high bio-available iron and poor socioeconomic conditions are important
      factors in this problem.

PMID- 16454051
TI  - Changes in body composition in lactating adolescent mothers.
AB  - We assessed changes in body composition in lactating adolescent mothers living
      under unfavorable socioeconomic and sanitary conditions. A total of 17 healthy
      primiparous adolescents under 17 years of age attending the Maternity Hospital of
      the city of La Plata, Argentina, were followed at 4 time points (15 days and 3, 6
      and 12 months postpartum) to assess, a) dietary intake, b) practice of physical
      activity, c) nutritional condition (weight, height, body mass index [BMI]
      according to age, and body composition by the sum of skinfold measurements), d)
      characteristics of lactation, and e) growth parameters of the child. The mean age
      of adolescents was 15.06 +/- 0.66 years (mean menarchal age, 11.59 +/- 0.80
      years). All adolescents breastfed up to 12 months postpartum, and maternal milk
      covered above 80% the baby intake (mean 7.06 +/- 2.54 breast feeds/day). While
      the daily intake of nutrients by adolescent mothers was constant up to 6 months
      postpartum, there was a modest decrease in that of proteins, carbohydrates and
      lipids 15 days and 12 months postpartum. The decrease in energetic intake during
      the same period was significant (p < 0.05). The practice of physical activity was
      classified as moderate during the follow-up period. Whereas mean basal percent of
      fat body mass (FBM) was 29.85 +/- 2.87, and decreased significantly at 6 (27.2%
      +/- 3.9%; p = 0.02) and 12 (26.1% +/- 3.9%; p = 0.002) months postpartum, changes
      in lean body mass (LBM) were not significant. In conclusion, lactating
      adolescents maintained LBM, whereas weight, FBM and BMI decreased markedly from 3
      months postpartum.

PMID- 16454052
TI  - [Comparison between two methods to estimate physical activity in obese women:
      accelerometry and self-administered questionnaire].
AB  - The aims of this study were to describe a female obese population according to
      their food intake and physical activity, and to compare two methods to estimate
      physical activity (PA). The study included a nutritional interview where a
      detailed dietary history was done, an initial clinical day in which measurements
      of body composition and basal metabolic rate (BMR) were carried out and an
      estimation of PA by means of a triaxial accelerometer and a PA questionnaire. The
      group of volunteers showed a mean BMI of 37.15 kg/m2, a waist/hip ratio of 0.82
      and a mean body fat mass of 43.34%. The average of BMR was 1720 Kcal/d and the
      CRNP of 0.79. The total caloric intake was 3344 Kcal/d with a energy-distribution
      of 43.1% Carbohydrates, 16.4% Proteins, 40.3% Lipids. Weight and BMI showed a
      positive correlation (p < 0.05) with the sedentary index (SI). Also, weight
      presented a positive correlation with the heart rate (p < 0.05). The estimates of
      PA derived from the questionnaire showed a positive correlation with the triaxial
      accelerometer (p < 0.01); and this one, revealed a negative correlation with the
      SI (p < 0.01). Anthropometric, metabolic and food intake variables are comparable
      to the results found in obese women from similar socioeconomic background. The
      estimates of PA according to the questionnaire were significantly correlated to
      the results of the triaxial accelerometer, thus confirming the validity of the
      questionnaire to assess PA in an obese population.

PMID- 16454053
TI  - [Evaluation of early manifestations of chronic no transmitted diseases risk in
      school population in Cali - Colombia].
AB  - Similar to other countries in America, Colombia and the Department of Valle
      present changes in their population structure and mortality suggesting an
      advanced epidemiological transition status. Grouped, chronic diseases represent
      the principal cause of death in municipalities with high urban concentration. To
      identify associated factors of chronic conditions later in life, school children
      stratified by age, socio-economic level and gender were studied. By random
      sampling of 14 schools 2.807 children were examined to measure: anthropometry,
      work capacity, food intake, sexual maturation, blood pressure, and blood levels
      of glucose and lipids. Weight and height for all ages and gender were lower than
      international reference but higher than in previous studies. On the contrary body
      mass indicators were higher. Work capacity adjusted for body weight was higher in
      low income children. Mean age of menarche was 11,9 years. The relative peak of
      growth was 11 years for girls and 14 for boys. Maturity was reached at 12 years
      in women and 17 in men. Blood lipids were considered high and borderline high in
      a large proportion of the students, while 19.5% had systolic blood pressure > or
      = 120 mm. and 24% diastolic > or = 70. Intake of protein and energy was adequate,
      but diet was high in fat and sugar. There was not deficiency in macro nutrients
      but dietary intake of some minerals was low, specially iron and calcium. The
      findings indicate a population with unbalanced diet and disturbing high body mass
      and lipid concentration that could represent in the future an increase in the
      already high prevalence of chronic diseases.

PMID- 16454054
TI  - [Food consumption patterns of children 4 to 14 years old in Valencia, Venezuela].
AB  - Results from a nutritional assessment are presented to establish the usual food
      consumption pattern of 438 children between 4-14 years of age, from a low income
      urban community in Valencia, Venezuela. Food intake data were collected through
      multiple 24 hours recalls and converted to individual food item weight in grams.
      Amounts of energy, macronutrients, iron, calcium, vitamin A, and vitamin C were
      estimated to compare them to national references. The food pattern was
      established according to intake frequency per food item and per food groups.
      Arepa was the most commonly consumed food item, and a main source of
      kilocalories, protein, carbohydrates, iron, and vitamin A. Unlike coffee, fruits
      were not among the most commonly consumed foods. Black beans were the main source
      of protein. Cookies and sodas were among the major sources of energy. Energy and
      nutrient intake were adequate, except for calcium (67% in preschoolers y 43% in
      school-aged children). Preschoolers' diet showed a better adequacy for all
      nutrients (p < 0.005), except for iron which was significantly higher in school
      aged children. Since children below 15 years old are still forming food behaviors
      and habits, they are an ideal group to develop nutritional education strategies
      to modify harmful patterns such as high intake of sodas, and low intakes of
      calcium rich foods.

PMID- 16454055
TI  - Effect of gamma irradiation on the microbiological quality of minimally processed
      vegetables.
AB  - The initial microflora of minimally processed celery and cabbage packaged under a
      modified atmosphere was determined. The samples came from the same producer and
      were sold in a supermarket chain of Santiago, Chile. Although neither E. coli nor
      Salmonella spp. were detected, initial total plate and Enterobacteriaceae counts
      were high (= 10(5) cfu/g), not meeting in most cases the specifications of the
      Chilean legislation. The D10 value for two strains of E. coli (ATCC 8739 and a
      wild type) inoculated as indicator microorganisms was determined. After
      irradiating with 5 D10 doses (1kGy), the variation of the microbial population
      and sensory quality during a 7 days storage period at 5 degrees C was studied. In
      irradiated celery, a reduction of 4.7 and 3.8 logs for total plate and
      Enterobacteriaceae counts respectively was observed. There was a decrease of 3.8
      and 3.6 logs in cabbage for total plate and Enterobacteriaceae counts
      respectively. In both irradiated and non-irradiated vegetables, neither E. coli
      nor Salmonella spp. were detected. An increase of 1.6 - 1.7 logs in both
      microbiological parameters in non-irradiated samples was observed during storage.
      In irradiated products, only celery showed an increase of 1.2 log in total plate
      count. Both Enterobacteriaceae count in the two vegetables and Total plate count
      in cabbage presented essentially no variation in time. No significant differences
      (p = 0.05) were detected in sensory total quality between the control and the
      irradiated vegetable and between days of storage.

PMID- 16454056
TI  - [Extraction and use of pigments from maize grains (Zea mays L) as colorants in
      yogur].
AB  - The aim of the present work was to determine the potential use of anthocyanins
      from maize grains as colorants in yogurt. Pigments were extracted from four
      native maize varieties (Arrocillo, Peruano, Purepecha and Conico), which possess
      a high anthocyanin concentration in the pericarp. Pericarp and aleurone layer
      were mechanicallly removed from grain using a Strong-Scott barley pearled. Yields
      of pericarp and aleurone layer fraction (PALF) were evaluated. Total anthocyanin
      content in this fraction was determined by a conventional spectrophotometric
      method and the anthocyanin profile was obtained by HPLC. One mg of anthocyanin
      extracts from the PALF was added to 100 g of a commercial plain yogurt. Yogurt
      samples were kept under refrigerated conditions and color and pH were monitored
      every 5 days interval, during three weeks. The yields of PALF were 48.4%, 55.1%,
      40.2%, and 40.0% for Arrocillo, Peruano, Conico and Purepecha varieties,
      respectivelly. The highest total anthocyanin content (259.4 mg of
      anthocyanins/100 g sample) was observed in Peruano PALF. The color of yogurts
      dyed with each of the four extracts was different. Yogurts dyed with Peruano and
      Arrocillo extracts showed a more intense reddish tone than those dyed with Conico
      and Purepecha. After 5 to 10 days under refrigerated storage, the color of all
      yogurt samples changed to a slight yellowish tone according to the Hue values,
      Nevertheless, these changes were not visually evident.

PMID- 16454057
TI  - [Cereal bars with soy protein and wheat germ, physicochemical characteristics and
      texture during the storage].
AB  - Studies analyzing cereal bars have reported on consumer characteristics and
      preferences in sensory analyses and on their market growth, however little has
      been published on their physicochemical data and texture properties. Thus the
      objective of this research was to provide information about the storage of a
      cereal bar formulation with high protein and vitamin levels based on soy protein
      and wheat germ, packaged in 3 different films (A: PET/PEBD; B: PETmet/PEBD; C:
      PET/PEBD/AL/PEBD), during 6 months under environmental conditions of temperature
      (25 +/- 2 degrees C) and relative humidity (56%). The moisture content, water
      activity, pH and total acidity of the cereal bars were determined. The textural
      measurements accompanied during storage were breaking strength, hardness and
      cohesiveness. The cereal bars presented variations in water activity (Aw),
      moisture content and total acidity during storage. The moisture content of the
      bars tended to increase, which led to a significant (p = 0.05) influence on the
      texture characteristics of breaking strength and hardness, in the different
      packaging films tested. The increase in the values for breaking strength (A:
      4756,5N; B: 5093,0N; C: 5575,6N) at 45 days of storage was attributed to a
      possible crystallization of the agglutinating syrup used for the bars. The
      textured soy protein used in the formulation could also have contributed to this
      fact due to its hygroscopic character, also interfering in the decrease in the
      cohesiveness measurements (deformation) with time. The effect of the different
      barrier properties of the packaging films tested was significant (p < 0.05) in
      the stability of the cereal bars during storage.

PMID- 16454058
TI  - [Chemical composition and bioactive compounds of flour of orange (Citrus
      sinensis), tangerine (Citrus reticulata) and grapefruit (Citrus paradisi) peels
      cultivated in Venezuela].
AB  - The purpose of this research was to evaluate the chemical composition and some
      bioactive compounds in the peel's flour of some of the most consumed citrus
      fruits cultivated in Venezuela. Chemical composition as well as some trace
      elements, ascorbic acid, carotenoids dietary fiber, total polyphenols and their
      antiradical efficiency, using the 2,2-diphenyl-1-picrylhidracyl (DPPH) were
      assessed in the dried peels of orange (Citrus sinensis), tangerine (Citrus
      reticulata) and white grapefruit (Citrus paradisi). Moisture, fat, protein and
      ash content for all samples showed statistical differences (p < 0.05).
      Tangerine's peel showed the highest magnesium and carotenoid content, while
      highest ascorbic acid and carotenoid content was found in the grapefruit's peel.
      Dietary fiber content presented significant high value in the tangerine peel. All
      samples presented high content of extractable polyphenols (4.33; 7.6 and 5.1
      g/100g). The highest antiradical efficiency was shown by the tangerine's peel,
      value which correlates with the polyphenol content. These results suggest that
      tangerine peel should be the most suitable, to reduce risk of some diseases such
      as cardiovascular and some associated to lipid oxidation. Studied samples are
      good sources of dietary fiber and phenolic compounds, whose use could be useful
      in the formulation of functional foods, taking advantage of the presence of
      dietary fiber and antioxidant compounds in only one ingredient.

PMID- 16454059
TI  - Challenges remain in developing pay-for-performance programs.

PMID- 16454060
TI  - Creative measures increase effective capacity in the emergency department.
AB  - Shady Grove Adventist Hospital has produced dramatic improvements in community
      access to care in its emergency department.

PMID- 16454061
TI  - ICU improvement project cuts central line infections 50%.
AB  - Intensive care units in Michigan hospitals used to have an average rate of
      central line infections. But following a two-year project to reduce medical
      errors and improve patient safety, Michigan's ICUs have reduced central i.v. line
      infections by nearly 50%.

PMID- 16454062
TI  - Stroke center multi-pronged approach yields large decrease in mortality.
AB  - Using a unique three-pronged strategy for improving stroke care, Swedish Medical
      Center has decreased mortality in stroke patients by 24%.

PMID- 16454063
TI  - Medicare finds that paying bonuses can improve performance.
AB  - Offering to pay bonuses to higher-performing hospitals has increased quality
      across the board, according to data from the first year of a Medicare
      demonstration project.

PMID- 16454064
TI  - Real time interactive CPOE increases compliance with best practices.
AB  - A seven-year veteran of computer-based physician order entry systems (CPOE),
      Meridian Health has begun embedding evidence-based best practice guidelines into
      a real-time interactive system.

PMID- 16454065
TI  - Taconic network brings EMRs to upstate New York practices.
AB  - For several years now the Taconic Health Information Network and Community
      (THINC) has been a national model for how physician practices, hospitals,
      reference labs, pharmacies, health insurers and employers can work together to
      share health information. THINC is now embarking on its most ambitious project to
      date--providing EMR system training, implementation and support to hundreds of
      physicians for as little as dollar 500 per provider per month.

PMID- 16454066
TI  - Paving the way toward a brighter future.

PMID- 16454067
TI  - What are the traits you most admire in successful leaders?

PMID- 16454068
TI  - The malpractice hard market is over--for most.

PMID- 16454069
TI  - Practice manager performance measures.

PMID- 16454070
TI  - 2006 final Medicare rule reduces physician payment by 4.4 percent.

PMID- 16454071
TI  - Medical errors. If you're not part of the solution, you're part of the problem.

PMID- 16454072
TI  - How integrated are your systems? Five considerations for practice management
      technology.

PMID- 16454073
TI  - Plugging in to progress. Electronic health records for every practice in the
      community.

PMID- 16454074
TI  - Knowledge is advantage. Using market research for competitive intelligence.

PMID- 16454075
TI  - A prescription for the ills of employee time and attendance.

PMID- 16454076
TI  - E-prescribing can be new tool in quality-care arsenal.
AB  - Electronic prescribing is one of the newest tools in health care's arsenal to
      help "Renew our Mission of Quality Patient Care," the theme of this year's
      National Medical Group Practice Week. Physicians--who can be reluctant to change
      their paper-based ways--are learning to write and send prescriptions via
      electrons rather than by pen or voice. Is your practice ready for e-prescribing?

PMID- 16454077
TI  - Brand-new world. Medical marketing the business way.
AB  - If someone mentioned the name of your practice, would y our patients, prospects
      and referring physicians feel, think or say? Are these images and adjectives
      consistent with the image you endeavor to build? Do people even know the vision
      for your practice? A well-planned brand strategy--aligned with overall business
      objectives--guides internal and external communications, new product
      introductions, acquisitions and mergers.

PMID- 16454078
TI  - Stormy weather. Preparing for and recovering from disasters.
AB  - Preparing for and recovering from disasters Planning is the most important thing
      a medical practice can do to prepare for a disaster. Learn from the experiences
      of a medical group in Florida that weathered four hurricanes in 2004. Its trials
      provide insights for other groups that might suffer calamities such as blizzards,
      floods, tornadoes, earthquakes, blackouts and even acts of terrorism.

PMID- 16454079
TI  - Touchdown! Jim LaBorde, CMPE, MGMA member and CEO, Western Surgical Group, Reno,
      Nev.

PMID- 16454080
TI  - [Direct access to the dental hygienist 2. Opinions of dental hygienists and
      dentists].
AB  - In this paper the opinions from dental hygienists and dentists are described
      concerning the question whether patients could visit the dental hygienist without
      being seen by a dentist first (access without referral). Eight of ten dental
      hygienists have a positive attitude towards the idea of access without referral.
      Dentists were much more sceptical about this idea. There are different opinions
      about which treatment, what kind of patients, which age groups etcetera a dental
      hygienist could treat without referral from the dentist. When access without
      referral becomes relevant, pilot studies are advised before implementing the
      concept of access to the dental hygienist without referral from the dentist.

PMID- 16454081
TI  - [Treatment of temporomandibular disorders in general practice. A survey in view
      of insurance claims].
AB  - In the eighth decade of the last century, about 3.5% of Dutch men and about 6% of
      Dutch women reported temporomandibular disorders. In 5% of the Dutch population
      temporomandibular disorders were diagnosed. It is unknown how many persons are
      seeking treatment for temporomandibular complaints. The aim of the present study
      was determining for how many persons and at which age of these persons treatments
      of temporomandibular disorders in general practices were reimbursed by an
      insurance company. On the basis of the yearly number of reimbursements by this
      insurance company, the yearly number of treatments of the Dutch population as a
      whole was estimated. The estimation was 0.87 treatments per 1.000 inhabitants,
      which figure was substantial lower as could be expected on the basis of the
      outcome of epidemiologic research projects. Within the limitations of this
      explorative study, a careful conclusion could be that only few treatments for
      temporomandibular disorders are charged by general practitioners. Probably, they
      are focussing on consultation and diagnosing, and not on treating the disease
      themselves.

PMID- 16454082
TI  - [Evidence-based management of temporomandibular dysfunction. Think before you
      begin!].
AB  - Nowadays, dentists are expected to base their treatment decisions on the
      strongest available evidence. This so-called evidence-based approach has four
      steps: the formulation of a clinical problem, the search for evidence, the
      evaluation of the evidence, and the treatment of the patient. As part of this
      approach, the strongest evidence comes from systematic reviews, which are free of
      any author-related bias. Since working according to the principles of evidence
      based dentistry is time consuming, dental schools should assist general
      practitioners through producing sufficient numbers of high-quality systematic
      reviews. The ever-increasing emancipation of patients stresses the need of
      adopting the principles of evidence-based dentistry. 'Think twice' should be the
      motto.

PMID- 16454083
TI  - Clinical challenges.

PMID- 16454084
TI  - [Minimal intervention with maximum results].

PMID- 16454085
TI  - [Candy sprays and -gels: effect on salivary flow and pH].
AB  - After seeing a child with dental erosion in a pediatric dental clinic the
      fondness and use of sweets were asked. With a questionnaire it became clear that
      recently various candy sprays and -gels are available to keep a sweet and fresh
      taste in the mouth at school. The buffer capacity of a number of sprays and gels
      were determined and they were tested in the mouth. The taste determines the
      increase in salivary flow rate. The effects of a taste stimulus on increasing the
      flow rate and decreasing the pH disappear within 2 until 3 minutes. Concluding:
      the Candy sprays and particularly the Juicy Drop Pop belong, from the dental
      point of view, to children sweets with high risk for dental caries and erosion.
      The use of these fluid sweets has to be reduced as much as possible.

PMID- 16454086
TI  - [A two-rooted maxillary incisor].
AB  - A case report is presented of a 14-year-old girl with a buccoapical fistula of
      tooth 22. The radiograph of the tooth revealed a periapical radiolucency and two
      roots. Endodontic treatment was conducted, followed by normal healing of the
      periapical area. Root division and additional roots of maxillary lateral incisors
      are rare phenomena.

PMID- 16454087
TI  - Estimation of seroprevalence of encephalomyocarditis in Dutch sow herds using the
      virus neutralization test.
AB  - Encephalomyocarditis virus (EMCV) has been found on pig farms worldwide and can
      cause myocarditis in young pigs and reproduction disorders in sows. So far,
      clinical signs of EMCV have not been reported in the Netherlands. The aim of this
      study was to estimate the seroprevalence of EMCV infection in Dutch sow herds. A
      total of 277 Dutch sow herds were randomly selected, from which 3237 serum
      samples were collected. These samples were tested for EMCV antibodies using the
      virus neutralization test (VN test). The apparent prevalence of EMCV antibodies
      was 9.3% in the total sow population, and the apparent herd prevalence was 58.8%.
      An exact determination of the prevalence of EMCV infections in the Dutch sow
      population was not possible because the characteristics of the VN test under
      field circumstances were not known. However, Dutch sow herds seem to be infected
      with EMCV because the distribution of positive blood samples in the tested sow
      population was significantly different from that expected if random false
      positive reactions had occurred.

PMID- 16454088
TI  - [Additional information on the article on acute babesiosis].

PMID- 16454089
TI  - [What are normal reference values?].

PMID- 16454090
TI  - [Facts about the Food Inspection Authority].

PMID- 16454091
TI  - [New committee chairman. Interview by Miel Bingen].

PMID- 16454092
TI  - [Changing special emergency slaughter as of January 1, 2006].

PMID- 16454093
TI  - [WAO makes room for WIA].

PMID- 16454094
TI  - [The change of the new veterinary drug legislation for delivery of veterinary
      drugs].

PMID- 16454095
TI  - [Alternatives for castration of ferrets].

PMID- 16454096
TI  - [Attention to veterinarian confidentiality].

PMID- 16454097
TI  - Oral health in aging societies: a global view.

PMID- 16454098
TI  - A systematic review of oral health assessment by nurses and carers for residents
      with dementia in residential care facilities.
AB  - This paper presents systematic review findings to best summarize the assessment
      of oral health and the use of oral assessment tools by nurses and carers for
      adults with dementia living in residential aged care facilities. The systematic
      review searched electronic databases for articles in English (1980 to 2002) and
      supplemented these with a secondary search of references cited in articles
      meeting the review inclusion criteria. Delineation is needed between a
      comprehensive dental examination conducted by a qualified dentist and a dental
      assessment screening by a carer, nurse, allied health professional or medical
      practitioner. Dental examinations should be supplemented with oral health
      assessments and screenings by trained nurses and carers to monitor residents'
      oral health, evaluate oral hygiene care interventions, act as a trigger to call
      in a dentist when required, assist with residents' individualized oral hygiene
      care planning and assist with triaging and prioritization of residents' dental
      needs. To date, the most comprehensive, validated and reliable assessment
      screening tool for use by nurses and carers with cognitively impaired
      institutionalized residents is the Brief Oral Health Status Examination. Other
      less comprehensive oral assessment tools that are useful for nurses and carers of
      institutionalized dementia populations include the Index of Activities of Daily
      Oral Hygiene and the Mucosal Plaque Score. These review findings presented
      evidence to support the use of oral assessment screening tools by nurses and
      carers for cognitively impaired residents living in residential aged care
      facilities. Few validated and reliable tools have been published for use by
      carers in the cognitively impaired residential care population, and continued
      evolution of oral assessment screening tools needs to embrace the complete
      spectrum of residents' levels of cognitive impairment.

PMID- 16454099
TI  - Development of a device for removing a partial denture in a patient with
      scleroderma.
AB  - Scleroderma is a chronic disease that has been associated with immune
      dysfunction. One of the oral manifestations is microsomia, a result of collagen
      deposition in the perioral issues. The complexity of treating these patients
      includes limited mouth opening ability, and difficulty inserting and removing
      dentures due to finger deformity. This article will describe an appliance
      specially designed especially for scleroderma patients, which facilitates
      treatment of the patient with removable partial dentures (RPD).

PMID- 16454100
TI  - Thalidomide in the management of recurrent aphthous ulcerations in patients who
      are HIV-positive: a review and case reports.
AB  - Recurrent Aphthous Ulceration (RAU) is an inflammatory ulcerative disease of
      unknown etiology. Although RAU are common in the general population, people with
      HIV disease may have ulcers that are large and painful and take a long time to
      heal. Local and systemic steroid therapy has been the traditional method of
      treatment for recurrent lesions. Recent studies have shown that systemic
      thalidomide therapy has the best efficacy in the treatment of major RAU in HIV
      seropositive patients. Two case histories of complete resolution of the RAU are
      presented. We have included recommended guidelines for prescribing thalidomide
      according to the System for Thalidomide Education and Prescribing Safety (STEPS)
      Program.

PMID- 16454102
TI  - Cephalometric evaluation of children with Down syndrome after early intervention
      with the stimulating plate.
AB  - The aim of stimulating plate therapy in patients with trisomy 21 is to correct
      orofacial dysfunctions and prevent the establishment of subsequent morphological
      characteristics such as protrusion of the incisors and pseudoprognathia. This
      study investigated the effectiveness of this type of therapy in improving
      skeletal traits of patients with Down syndrome. The lateral cephalograms of 22
      consecutive juveniles with Down syndrome, whose orofacial dysfunctions had been
      successfully treated with a stimulating plate according to Castillo Morales in
      infancy (17 months +/- 24 months), were examined 136 months on average (minimum
      of 78 months, maximum of 231 months) after initiation of treatment. In 16 of the
      22 patients, the anomaly-typical bialveolar protrusion of the anterior teeth was
      diagnosed. The cephalometric results indicated larger values of cephalometric
      parameters concerning cranial base and maxilla, and markedly larger mandibular
      cephalometric values when compared to untreated children with Down syndrome.
      These results show that a stimulating plate may not always be indicated in
      patients with Down syndrome with a skeletal Class III pattern and minor orofacial
      findings.

PMID- 16454101
TI  - Salivary sIgA and cortisol: markers for functional dependence in older adults.
AB  - Elderly persons with health problems and physical limitations have reduced
      independence. Since poor functional ability is a known risk factor for disease
      among older populations, including oral disease, this study was undertaken to
      assess whether salivary defense factors and the stress hormone cortisol are
      significant markers for functional dependence. Oral examinations; salivary and
      microbial analyses; and interviews using the Activities of Daily Living (ADD
      index, the Mini Nutritional Assessment (MNA) and the Perceived Life Stress
      Questionnaire (PLSQ) were conducted for 123 dentate subjects. Of the subjects, 80
      lived independently in the community or in apartments at the Baycrest Centre for
      Geriatric Care in Toronto, Canada, and 43 resided in the Baycrest nursing home or
      the Baycrest Hospital. Whole saliva samples were assayed for total secretory
      immunoglobulin A (sIgA), sIgA1, sIgA2, total protein and cortisol using ELISA.
      Dependent residents in the nursing home/hospital scored significantly lower in
      the nutritional assessment, had higher mean PLSQ scores, increased total protein
      and cortisol concentrations, and reduced salivary flow rates in comparison to
      ambulatory residents in the community/apartments. In multivariable logistic
      regression, factors associated with functional dependence were: being male,
      perceiving income as inadequate, having low salivary flow rate and drinking less
      than 5 cups of water per day. These results indicate that salivary flow and
      cortisol may be useful markers of functional dependence; however, the ability of
      these markers to predict functional decline cannot be confirmed until
      longitudinal studies are conducted.

PMID- 16454104
TI  - OSHA is pressing ORs to adopt safety scalpels but surgeons resist.

PMID- 16454103
TI  - Chewing ability of the long-term hospitalized elderly.
AB  - We investigated the chewing ability of 260 (25 percent men) long-term
      hospitalized elderly patients 60 years of age and older in Laakso hospital,
      Helsinki, Finland, in relation to their mastication capacity, sore mouth and
      degree of dependence. The subjects' (mean age 83.3 years, SD = 8.1 years)
      mastication capacity was determined by a specialist dentist by means of: (a)
      number of functioning teeth and dentures; (b) modified Eichner Index; and (c) the
      Eichner Score, based on the index. Based on the information given by the nursing
      staff, an indicator of chewing ability was created. The chewing ability was poor
      for 55 percent, limited for 17 percent, moderate for 14 percent and excellent for
      14 percent. Excellent or moderate ability to chew was related to a subject's
      lesser degree of dependence (OR = 1.5; p = 0.02) and higher Eichner Score (OR =
      1.3; p = 0.000). More attention should be focused on mastication capacity of the
      hospitalized elderly.

PMID- 16454105
TI  - Director's Cup rewards OR teams for moving from good to great.

PMID- 16454106
TI  - ASA advisory on anesthesia awareness.

PMID- 16454107
TI  - What OSHA says about safety scalpels.

PMID- 16454108
TI  - 'Snapshot' helps managers spot trends.

PMID- 16454109
TI  - Cardiac complications linked to solution.

PMID- 16454110
TI  - Credentialing: what managers need to know.

PMID- 16454111
TI  - Planning for a dedicated coder.
AB  - Although there are a number of complaints about the complexity of coding rules
      and regulations, physicians and facilities are still responsible for knowing the
      guide- lines-or employing someone who does. Also, the practice needs to establish
      processes to monitor compliance with payor guidelines. The good news is that
      physicians have an opportunity to improve their income through appropriate
      coding. According to MD Compliance Alert, April 15, 2002: "In fact, improper
      coding is the number one most visible and correctable problem in any given
      practice. Corrected, it can have the simplest, biggest, and quickest impact on
      most doctors' income".

PMID- 16454112
TI  - Modifications and revisions to program standards.

PMID- 16454113
TI  - Marketing goals and strategies.

PMID- 16454114
TI  - Comprehensive care plus creative architecture.
AB  - The delivery of high-quality, comprehensive cancer care and the treatment
      environment go hand in hand with the patient's recovery. When the planning and
      design of a comprehensive cancer care program runs parallel to the operational
      expectations and functional standards, the building users (patients, staff, and
      physicians) benefit significantly. This behavioral response requires a sensitive
      interface during the campus master planning, architectural programming, and
      design phases. Each building component and user functioning along the "continuum
      of care" will have different expectations, programmatic needs, and design
      responses. This article addresses the community- and hospital-based elements of
      this continuum. The environment does affect the patient care and the care-giving
      team members. It may be a positive or, unfortunately, a negative response.

PMID- 16454115
TI  - Where there is a will, there is a way: networks as a means of cancer control.
AB  - A key challenge in cancer control is the need for translational research to link
      discovery research with improved health outcomes. In British Columbia, we have
      built upon the idea of communities of practice to develop networks that will meet
      our cancer-control mandate.

PMID- 16454116
TI  - Design of the ideal workplace: strategies and lessons learned.
AB  - As the need for cancer care grows, so does the need for facilities that address
      the needs of patients and their families. The design of a cancer center must
      support the treatment and interventional process and maximize the feeling of
      comfort and reassurance while the patient is present for care. This article will
      focus on outpatient cancer-care design and the issues involved to assist the
      administrator in leading this effort.

PMID- 16454117
TI  - Cassette based digital X-ray systems: evaluating the Konica Minolta Xpress CR.
AB  - Cassette-based digital x-ray systems--also called computed radiography (CR)
      systems--are flexible and affordable, qualities that have secured their continued
      use in clinical settings. In this follow-up to our August 2001 Evaluation of CR
      systems, we examine the Konica Minolta Xpress CR. Our testing examines the
      ability of the Xpress CR to provide at least the same amount of diagnostic
      information as screen-film systems, while significantly increasing the overall
      efficiency of a radiology department. This article also includes updated
      information on the new products now offered by the suppliers whose CR systems we
      examined in August 2001. In addition, it describes the general developments that
      have occurred in CR technology. These developments include the use of new
      phosphor types to increase image quality and the wider implementation of wall
      mounted touchscreens to improve workflow.

PMID- 16454118
TI  - The problem with "keepsake" fetal ultrasound: ECRI and other medical
      professionals cite potential risks.
AB  - An increasing number of businesses are using ultrasound scanners to provide
      expectant parents with souvenir pictures and videos of their fetuses, without any
      medical purpose. These "keepsake ultrasound" operations could have many negative
      effects: for example, they may cause hospitals to lose referrals, and they may
      create legal and regulatory problems both for the operators of the businesses and
      for the manufacturers and distributors that sell them their equipment; there is
      even the possibility that mothers or fetuses could suffer harm. ECRI and several
      other organizations oppose the practice, although efforts to stop or regulate it
      have had little impact so far.

PMID- 16454119
TI  - FCC to begin issuing licenses for use of mobile radios in the 460 to 470 MHz
      band.
AB  - The U.S. Federal Communications Commission (FCC) has stated that after December
      31, 2005, it will begin issuing licenses for use of private land mobile radios
      (PLMRs) in the 460 to 470 MHz frequency band. Medical telemetry systems operating
      in this band after December 31 will therefore be at increased risk for
      interference, which could compromise patient safety. Any medical facility in the
      vicinity of a PLMR could be affected.

PMID- 16454120
TI  - Disconnected power cord shuts down Drager Medical Evita ventilator.

PMID- 16454121
TI  - Air-detection settings for general-purpose infusion pumps.

PMID- 16454122
TI  - Power cord strain relief may pull out of Kendall 7325 SCD Response Compression
      System.

PMID- 16454123
TI  - Manufacturer-recommended cleaning products and their alternatives.

PMID- 16454124
TI  - HIV/AIDS in Pakistan.

PMID- 16454125
TI  - Leptin levels in pre and post menopausal Pakistani women.
AB  - OBJECTIVE: To evaluate the correlation of fasting serum leptin levels with
      anthropometric measurements and menopausal status, in women. METHODS: The study
      comprised of 80 non-obese women who were divided into 2 groups as pre-menopausal
      (n=46) and post-menopausal (n=34). Anthropometric measurements i.e. height,
      weight, waist and hip circumference were measured for all the subjects and the
      Waist-hip Ratio (WHR) and Body Mass Index (BMI) were calculated from these
      measurements. A fasting venous blood sample was taken from all the subjects and
      serum leptin concentrations were determined by ELISA. RESULTS: A comparison of
      the mean values for BMI and WHR between the two groups showed a non significant
      difference. Within each group, significant associations were noted between the
      fasting serum leptin level and values of BMI and WHR. A comparison of the mean
      serum leptin concentrations between the two groups, showed a highly significant
      difference (p<0.001). CONCLUSION: Our results indicate that in the non-obese
      women of our population, leptin levels associate with BMI and WHR and together
      with menopausal status seem to be important determinants of serum leptin levels.

PMID- 16454126
TI  - Phloroglucinol in irritable bowel syndrome.
AB  - OBJECTIVE: To determine the efficacy and tolerability of phloroglucinol, an
      antispasmodic agent in the treatment of Irritable Bowel Syndrome (IBS). METHODS:
      It was an open label (quasi interventional) study. One hundred patients coming to
      the gastroenterology clinics of Aga Khan University Hospital with IBS as defined
      by the Rome II criteria were enrolled between February 2004 and September 2004 to
      participate in the trial and were treated as outpatients. Phloroglucinol (Himont)
      50mg orally three times daily was given for two months. Symptoms were assessed
      before and during treatment using a questionnaire. RESULTS: One hundred patients
      were enrolled in the study. Of them 61% (61/100) were males and 39% (39/100) were
      females. Their mean age was 41 +/- 14 years. Sixty-eight patients completed the
      study and 28 dropped out. On Phloroglucinol treatment there was an overall
      statistically significant improvement in abdominal pain (p<0.001), frequency of
      stools per day (p<0.001), urgency (p<0.001), passage of mucus per rectum
      (p<0.001), sense of incomplete defecation (p=0.001) and bloating (p=0.001).
      However, no response was seen in the feature of straining in both genders
      (p=0.676). The difference in response to treatment according to gender separately
      showed statistically significant improvement in the sense of incomplete
      defecation in females alone (p=0.003). CONCLUSION: Phloroglucinol in a dose of
      50mg three times daily is effective and well tolerated by the IBS patients. It
      relieves most of the symptoms of IBS.

PMID- 16454127
TI  - Significance of cytogenetic abnormalities in acute myeloid leukaemia.
AB  - OBJECTIVE: To evaluate the role of karyotype in acute myeloid leukaemia (AML) as
      a predictor of response to induction chemotherapy. METHODS: A cross-sectional
      study was carried out at the department of Pathology and Oncology, Aga Khan
      University Karachi from January 2003 to January 2005. Newly diagnosed patients
      with denovo AML admitted to the hospital were included in the study. Diagnosis of
      AML was based on FAB criteria, immunophenotyping and cytogenetic studies. They
      were treated according to standard protocols (combination of anthracycline and
      cytarabine -3+7) and those who had acute promyelocytic leukaemia additionally
      received all- trans retinoic acid (ATRA). RESULTS: A total of 56 patients were
      enrolled, 4 were excluded due to inadequate cytogenetic analysis and the
      remaining patients entered the study protocol. There were 32 males and 20 females
      with mean age of 31.3 years (range 9 months to 73 years). Thirty-five (67.3%)
      patients had normal karyotype while 17 (32.7%) were found to have cytogenetic
      abnormalities. Eleven patients did not receive treatment at our hospital. Half of
      the (51.2%) patients out of remaining 41 achieved complete remission on bone
      marrow examination after receiving induction chemotherapy. In favourable risk
      group 3/3 (100%) achieved complete remission (CR) while 15/32 (46.9%) in
      intermediate risk group and 3/6 (50%) in unfavourable risk group. There was low
      CR rate in patients with high white cell counts. CONCLUSION: The frequency of
      cytogenetic abnormalities in AML and response to induction chemotherapy was low
      when compared with international data possibly due to the small sample size.
      However, there was a clear difference in CR rates between favourable and
      unfavourable risk groups.

PMID- 16454128
TI  - Morbidity pattern and utilization of a primary health care center in a low
      socioeconomic area of Karachi.
AB  - OBJECTIVE: To identify the morbidity pattern according to age, gender and
      seasonal variation using the ICD coding and the utilization of Primary Health
      Care (PHC) center services in a demographically defined community. METHODS: The
      data collected from 2001-2003 was analyzed using the International Classification
      of Diseases-10 (ICD-10) coding for identifying the morbidity patterns presenting
      at the PHC Center. The age and gender distribution of the patients and the
      seasonal variation of few diseases were noted. Only the residents of the area
      visiting the center for preventive or curative services were included. A
      structured performa was designed to enter the age, gender, disease and ICD codes.
      The faculty was trained for using the coding system. RESULTS: A total of 13,519
      patients visited the PHC during three-year period. On an average, 376 patients
      were seen during a month with male to female ratio of 1:2. The most common
      diseases presented belong to the respiratory system, followed by infections or
      parasitic infestations and diseases of the reproductive system. The women
      presented for first visit of antenatal check up were 960 out of 4614 women of
      reproductive age group. Among the adult population, 391 (6%) presented with
      hypertension, 64 (1%) were Type 2 diabetics and 86 (1.3%) were asthmatics. The
      paediatric population analysis showed that 918 (13%) had upper respiratory
      infections and 1339 (19%) had diarrhoea. CONCLUSION: Problem oriented medical
      records from health centers, computerized in a uniform standardized way, can give
      extensive information about the content and burden of health problems in family
      practice and presumably public health.

PMID- 16454129
TI  - The accuracy of ultrasound in the diagnosis of congenital abnormalities.
AB  - OBJECTIVE: To determine the accuracy of ultrasound in the diagnosis of congenital
      abnormalities at the Aga Khan University Hospital, Karachi. METHODS: The data of
      congenital abnormalities was obtained from the obstetrical database and medical
      records of all cases complicated by congenital abnormalities, delivering from
      January 2001 to December 2003 and was reviewed. Antenatal ultrasounds had been
      performed by operators with different level of experience. In addition this data
      was retrieved from the termination and Congenital anomaly register. A structured
      data collection form was used to collect information of different variables of
      interest. RESULTS: Congenital abnormalities, complicated 2.8% (n=170), of all
      deliveries, including all cases of termination of pregnancy, stillbirth and live
      births. Out of the total, 11.6% occurred in women above the age of 35 years.
      Consanguinity was found in 18.2% cases. Prenatal diagnosis was made in just under
      half of the cases (48.8%). Central nervous system and renal abnormalities were
      commonly diagnosed. However, facial defects, heart defects or skeletal defects
      were more commonly missed. CONCLUSION: Antenatal ultrasound successfully
      diagnosed foetal abnormalities in 48.8% of cases, and more than 90% Central
      Nervous system defects and renal abnormalities. In contrast about a quarter of
      Cardiac defects and none of the facial defects were detected. Based on these
      findings we recommend that the Sonologist should incorporate four chamber view of
      the heart and also look at the face carefully.

PMID- 16454130
TI  - Psycho-social consequences of secondary infertility in Karachi.
AB  - OBJECTIVE: To explore the experiences of social consequences among women
      suffering from secondary infertility. METHODS: Descriptive case series of 400
      women with secondary infertility attending tertiary care hospitals in Karachi,
      Pakistan. RESULTS: More than two thirds (67.7%) of women stated that their
      inability to give live births or give birth to sons had resulted in marital
      dissonance. The respondents had been threatened for divorce (20%), husband's
      remarrying (38%) or to be returned to their parent's home (26%) by their in laws
      or husbands. Majority (68%) of the women threatened did not have any live births.
      However, those who had live births (32%) had a girl child only followed by
      difficulty in conceiving again. Secondary infertility was described as a cause of
      violence against infertile women. The women reported that they were being
      physically and verbally abused by husbands (10.5%) and in-laws (16.3%) for being
      infertile. Nearly 70% of women facing physical abuse and 60% of the women facing
      verbal abuse suffered severe mental stress. CONCLUSION: The experience of
      infertility is a stressful condition itself. This becomes particularly traumatic
      with previous pregnancies ending up in abortions, stillbirths and neonatal/infant
      deaths or the live births being daughters only. However, it subjects the woman to
      contempt and exploitation resulting in severe psychological.

PMID- 16454131
TI  - Small B cell Non-Hodgkins Lymphoma in Pakistan.
AB  - OBJECTIVE: To study the pattern of small B cell lymphomas in Pakistan. METHODS:
      This descriptive study was carried out at the Aga Khan University Hospital
      pathology department including 1721 cases of Non-Hodgkins Lymphoma (NHL)
      diagnosed during a period of five years (1998-2002) and classified according to
      REAL/WHO classification. The antibodies used included Leukocyte Common Antigen
      (LCA), Pan B (CD20, CD79a), Pan T (UCHL-1), Bcl 2, Mib 1(Ki 67) and Cyclin D1
      (Dako, Denmark). RESULTS: Out of the 1721 NHL cases, only 140 (8.1%) could be
      categorized as small B-cell NHL. The study group comprised small lymphocytic
      lymphoma/chronic lymphocytic leukemia (58 cases; 41.4%) followed by follicular
      lymphoma (46 cases; 32.9%), mantle cell lymphoma (15 cases; 10.7%), extra nodal
      marginal zone B cell lymphoma of MALT type (15 cases; 10.7%), lymphoplasmacytic
      lymphoma (5 cases; 3.6%) and splenic marginal zone B-cell lymphoma (1 case;
      0.7%). No case of nodal marginal zone lymphoma was diagnosed. The age ranged from
      18 to 98 years with a mean and median of 54.64 and 58.50 years respectively.
      Small B-cell NHL was more common in males; with male to female ratio of 2.1.
      Majority of the small B-cell NHL were nodal at presentation with a nodal to
      extranodal ratio of 3.4. CONCLUSION: It is concluded that the frequency of these
      small B-cell NHL is very low in our population in contrast to the western
      literature. Further studies based on epidemiologic and etiological factors are
      required to look into this marked difference of occurrence of these indolent
      lymphomas.

PMID- 16454132
TI  - Massive primary postpartum haemorrhage: setting up standards of care.
AB  - OBJECTIVE: To review practice of massive primary postpartum haemorrhage
      management and develop a protocol. METHODS: Cross-sectional study conducted at
      the Department of Obstetrics and Gynaecology at Aga Khan University Hospital,
      Karachi between January 1, 2003 and July 31, 2004. Women with primary postpartum
      haemorrhage and had blood loss > or = 1000ml were included in the study. Medical
      record files of these women were reviewed for maternal mortality and morbidities
      which included mode of delivery, possible cause of postpartum haemorrhage,
      supportive, medical and surgical interventions. RESULTS: Approximately 3%
      (140/4881) of women had primary postpartum haemorrhage. 'Near miss' cases with
      blood loss > or = 1500ml was encountered in 14.37% (20/140) of these cases. Fifty
      six percent (18/32) of the women who had massive postpartum haemorrhage delivered
      vaginally. Uterine-atony was found to be the most common cause, while care in
      High Dependency Unit (HDU) was required in 87.5% (28/32) of women. In very few
      cases balloon tamponade (2-cases) and compression sutures (2-cases) were used.
      Hysterectomy was performed in 4-cases and all of them encountered complications.
      Blood transfusions were required in 56% of women who had massive postpartum
      haemorrhage. CONCLUSION: This study highlights the existence variable practices
      for the management of postpartum haemorrhage. Interventions to evaluate and
      control bleeding were relatively aggressive; newer and less invasive options were
      underutilized. Introduction of an evidence-based management model can potentially
      reduce the practice variability and improve the quality of care.

PMID- 16454133
TI  - Anaesthesia for caesarean section in patients with cardiac disease.
AB  - This review contains material sourced from Med-Line and Pub-Med, search year 2002
      2004. Material selected was pertaining to common cardiac ailments in pregnancy.
      Congenital cardiac problems i.e. Tetralogy of Fallot (TOF), Atrial Septal Defect
      (ASD), Ventricular Septal Defect (VSD), Eisenmengers syndrome, valvular heart
      disease, i.e. mitral stenosis, mitral regurgitation, aortic stensois and aortic
      regurgitation are discussed. Other cardiac conditions associated with pregnancy
      are pulmonary hypertension and peri-partum cardiomyopathy. Arrhythmias during
      pregnancy, vary from isolated premature to supra-ventricular and ventricular
      tachycardia, management is similar to non-pregnant patients. This review
      summarizes the current management of a parturient with cardiac disease requiring
      surgical delivery. Regional anaesthesia techniques are preferred as reflected in
      the current literature for patient with cardiac disease with minor alterations
      such as slow establishment of epidural for caesarean section or continuous spinal
      anaesthesia with very small incremental doses of local anaesthesia, maintaining
      the patient's SVR with vasopressors and fluid, monitoring of the fluid regimen
      with CVP and in some cardiac function with Swan Ganz catheter. Patients with
      Eisenmenger syndrome, pulmonary hypertension, should be advised to avoid
      pregnancy. In conclusion with vast advancements in obsterics care, improvements
      in cardiac surgery, many patients with cardiac disease can now be safely
      delivered surgically by skillful anaesthesiologists who are aware of the common
      potential intra-operative problems and the ability to respond to undesired events
      immediately.

PMID- 16454134
TI  - Retrocaval ureter with hydronephrosis.
AB  - Retrocaval ureter is one of the rare congenital anomalies. We report a case of
      retrocaval ureter who presented with right lumbar pain, renal stone and
      hydronephrosis. The diagnosis was made on intravenous urography which showed
      typical "J" shape deformity in the proximal dilated ureter with moderate
      hydronephrosis. CT scan mapped out the course of ureter. The patient was operated
      and findings were confirmed. The ureter was transected near the pelvis, renal
      stone removed and a uretero-uretral anastomosis with anteriorisation of the
      ureter performed.

PMID- 16454135
TI  - Minimally symptomatic severe hypercalcaemia in a patient with parathyroid
      carcinoma.
AB  - The case of a 38 years old man with generalized pains fatigue, anorexia,
      constipation, polyuria serum calcium level of 20.6mg/dl in paired renal function
      parathyroid hormone is presented. Sestamibi scan showed a functioning left
      inferior parathyroid tumor, which was successfully removed. Before surgery he was
      managed with rehydration, diuretics and pamidronate infusion. Five months post
      surgery the serum calcium levels are normal and renal function has improved.

PMID- 16454136
TI  - The role of prophylactic intra-aortic balloon pump counterpulsation (IABP) in
      emergency non-cardiac surgery.
AB  - Patients with recent myocardial infarction (MI), congestive heart failure, severe
      angina, or uncorrected multivessel coronary artery disease are at increased risk
      of cardiac complications after urgent major non-cardiac surgery. Although
      invasive haemodynamic monitoring and preoperative optimization of cardiac status
      may lead to some reduction in the rate of perioperative cardiac events, the
      mortality from such events still remains high. The use of an intra-aortic balloon
      pump (IABP) may play a role in such patients by improving the function of the
      injured heart. We report our experience with the use of perioperative IABP in a
      patient with unstable angina and recent MI who underwent urgent cholecystectomy.
      There were no perioperative cardiac events while the IABP was in place. The
      anaesthetic concerns, intraoperative and postoperative monitoring and care and
      usefulness of IABP will be discussed.

PMID- 16454137
TI  - Fludarabine induced autoimmune haemolytic anaemia in a patient with chronic
      lymphocytic leukaemia.
AB  - Autoimmune haemolytic anaemia following fludarabine is an uncommon complication
      and previously treated patients are at higher risk. We describe a case of 57-year
      old lady with chronic lymphocytic leukaemia; she received intermittent courses of
      alkylating agents and purine analogue, fludarabine. Reintroduction of fludarabine
      for her relapsing disease induced autoimmune haemolytic anaemia. Numbers of cases
      have been reported regarding autoimmune haemolytic anaemia following fludarabine
      administration, but none have been published from our part of the world. Normally
      T-cell suppresses autoreactive lymphocytes that can produce autoantibodies.
      Suppression of T-cells by fludarabine, in addition to the underlying disease
      process appears to be a contributory factor for autoimmune haemolytic anaemia.

PMID- 16454138
TI  - The differences between physicians and the surgeons in prescription pattern of
      benzodiazepines.

PMID- 16454139
TI  - Cardiovascular risk factors paradox in maintenance dialysis patients! A spurious
      hypothesis or a hard core reality?

PMID- 16454140
TI  - Systems biology: the gut-brain-fat cell connection and obesity.

PMID- 16454141
TI  - The use of probiotics in the treatment of irritable bowel syndrome.

PMID- 16454142
TI  - The summit on healing: honoring diversity, finding common ground.

PMID- 16454143
TI  - Healing the wounds of war: Gaza diary.

PMID- 16454144
TI  - The cardioprotective benefits of monounsaturated fatty acid.

PMID- 16454145
TI  - Ineffectiveness of zinc gluconate nasal spray and zinc orotate lozenges in common
      cold treatment: a double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Zinc gluconate and zinc acetate lozenges have been reported to
      shorten the duration of common colds in a dose-response manner when the amount of
      the active ingredient, positively charged zinc ions, is sufficient. OBJECTIVE: To
      improve results using a zinc gluconate nasal spray with zinc orotate lozenges.
      DESIGN: Double-blind, placebo-controlled clinical trial. SETTING: Private
      physician's clinic in Austin, Texas. PARTICIPANTS: Seventy-seven volunteers, all
      of whom had 2 or more signs and symptoms of common colds (with at least 1 nasal
      symptom) on enrollment in the study. METHODS: Zinc gluconate nasal spray (10
      mmol) or placebo was used every 15 to 30 minutes, and lozenges were used each
      several hours to reduce duration and severity of common colds. An intention of
      treatment was to keep the nasal tissues wet with zinc gluconate solution during
      wakeful hours. RESULTS: After 7 days of treatment, 10 of 16 (63%) zinc-treated
      patients were asymptomatic compared to 9 of 17 (53%) placebo-treated patients (P
      = .57). This treatment caused olfactory region pain in some patients and did not
      reduce the duration or severity of common colds. Treatment did not produce
      anosmia, which has been reported in other studies following olfactory region
      administration of ionic zinc in many species and in humans from zinc nasal sprays
      and gels. CONCLUSION: We contend that it is unethical to introduce any
      potentially permanent anosmia-inducing agent such as zinc or other heavy metals
      into the interior of the nose in a manner that could result in contact with the
      olfactory region to treat a temporary discomfort such as a common cold or
      allergy. We found no reason to recommend intranasal zinc gluconate or zinc
      orotate lozenges in treating common colds.

PMID- 16454147
TI  - Effect of a proprietary Magnolia and Phellodendron extract on weight management:
      a pilot, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To determine the efficacy of a dietary supplement ingredient
      containing proprietary extracts of Magnolia officinalis and Phellodendron
      amurense in helping overweight, otherwise healthy, premenopausal female adults,
      who typically eat more in stressful situations manage their body weight. DESIGN:
      Randomized, double-blind, placebo-controlled clinical study. Setting Miami
      Research Associates, a clinical research organization consisting of 32 board
      certified physicians, Miami, Fla. SUBJECTS: Healthy, overweight (BMI 25 to 34.9),
      premenopausal female adults, between the ages of 20 and 50 years, who typically
      eat more in response to stressful situations and scored above the national mean
      for women on self-reported anxiety. INTERVENTIONS: Two-hundred-fifty-mg capsules
      or identical placebo capsules 3 times a day for 6 weeks. MAIN OUTCOME MEASURES:
      Salivary cortisol levels, weight change, psychological measures of stress and
      anxiety. RESULTS: Twenty-eight subjects completed the study. Extracts of M
      officinalis and P amurense were well tolerated. There was a significant weight
      gain during the study for the placebo group (P < ,01), but no significant weight
      gain for the group receiving extracts of M officinalis and P amurense (P < .89).
      Paired t-tests comparing baseline to post-treatment weight showed an average gain
      of 1.5 kg in the placebo group and no change in the treatment group (P = .89).
      When groups were divided into gainers (ie, participants who gained at least 1 kg
      or more) and maintainers or losers, 75% of the control group were gainers versus
      37% of the treatment group (P < .04). There was a nonsignificant trend for
      lowered average cortisol in the treatment group at the end of the study (group X
      time interaction, F = 1.1, P < .15). This difference was due to a treatment
      effect on evening cortisol. There was a marginally significant group X time
      interaction (P = .06), showing the treatment group tended to have lower levels of
      cortisol in the evening, whereas the control group tended to have higher levels
      of cortisol in the evening. Bedtime cortisol levels decreased in the treatment
      group and increased in the placebo group. Participants in both the treatment and
      placebo groups had improved scores on a number of psychological measures during
      the study. There was a correlation between perceived stress and weight change.
      CONCLUSION: The results of this pilot clinical study indicate that obese subjects
      who eat in response to stress may benefit from taking a dietary supplement
      ingredient containing proprietary extracts of M officinalis and P amurense. The
      mechanism of action appears to be through reduction of cortisol levels and
      possibly perceived stress, thereby helping participants maintain body weight. The
      sample size was small, however, and there was higher attrition in the control
      group than in the treatment group.

PMID- 16454146
TI  - Randomized, controlled, six-month trial of yoga in healthy seniors: effects on
      cognition and quality of life.
AB  - CONTEXT: There are potential benefits of mind-body techniques on cognitive
      function because the techniques involve an active attentional or mindfulness
      component, but this has not been fully explored. OBJECTIVE: To determine the
      effect of yoga on cognitive function, fatigue, mood, and quality of life in
      seniors. DESIGN: Randomized, controlled trial comparing yoga, exercise, and wait
      list control groups. PARTICIPANTS: One hundred thirty-five generally healthy men
      and women aged 65-85 years. INTERVENTION: Participants were randomized to 6
      months of Hatha yoga class, walking exercise class, or wait-list control.
      Subjects assigned to classes also were asked to practice at home. MAIN OUTCOME
      MEASURES: Outcome assessments performed at baseline and after the 6-month period
      included a battery of cognitive measures focused on attention and alertness, the
      primary outcome measures being performance on the Stroop Test and a quantitative
      electroencephalogram (EEG) measure of alertness; SF-36 health-related quality of
      life; Profile of Mood States; Multi-Dimensional Fatigue Inventory; and physical
      measures related to the interventions. RESULTS: One hundred thirty-five subjects
      were recruited and randomized. Seventeen subjects did not finish the 6-month
      intervention. There were no effects from either of the active interventions on
      any of the cognitive and alertness outcome measures. The yoga intervention
      produced improvements in physical measures (eg, timed 1-legged standing, forward
      flexibility) as well as a number of quality-of-life measures related to sense of
      well-being and energy and fatigue compared to controls. CONCLUSIONS: There were
      no relative improvements of cognitive function among healthy seniors in the yoga
      or exercise group compared to the wait-list control group. Those in the yoga
      group showed significant improvement in quality-of-life and physical measures
      compared to exercise and wait-list control groups.

PMID- 16454148
TI  - Communication about complementary and alternative medicine: perspectives of
      primary care clinicians.
AB  - BACKGROUND: People in the United States are using complementary and alternative
      medicine (CAM) increasingly while they are also receiving conventional care.
      National population-based surveys and studies in primary care settings have
      documented inadequate communication about CAM between patients and their
      conventional healthcare providers. Most studies about CAM communication have
      surveyed urban practices and focused on physicians. Information about how
      physicians and non-physician in rural areas clinicians communicate with their
      patients about CAM is needed to develop strategies for improving the quality of
      care for patients in rural areas. OBJECTIVE: To investigate how primary care
      clinicians in the Kentucky Ambulatory Network (KAN) communicate with patients
      about CAM and to determine interest in additional education about CAM. METHODS: A
      self-administered survey was mailed to 112 community clinicians in a research
      network of largely rural practices. KAN members include primary care physicians,
      nurse practitioners, certified nurse midwives, and physician assistants
      practicing in 32 counties in central and eastern Kentucky. RESULTS: Of 102
      deliverable surveys, 65 (64%) were returned. Sixty-one (94%) clinicians reported
      patient CAM use. Few clinicians consistently asked patients about CAM. A positive
      attitude toward patient CAM use was associated with clinician comfort in advising
      patients. Most clinicians recommended CAM to patients. Seventy percent of KAN
      clinicians expressed interest in continuing education about CAM. CONCLUSIONS:
      Kentucky primary care clinicians are aware of their patients' CAM use and are
      motivated to learn more about CAM so that they can appropriately advise their
      patients. They need evidence-based, clinically relevant education about CAM to
      provide better patient care.

PMID- 16454149
TI  - Efficacy of auricular acupressure as an adjuvant therapy in substance abuse
      treatment: a pilot study.
AB  - CONTEXT: Substance abuse and its related problems have become a serious public
      health issue, particularly in underserved border and rural communities.
      Conventional therapies have not always been effective. Literature regarding the
      use of auricular acupressure in substance abuse treatment is limited. OBJECTIVE:
      To examine the efficacy of auricular acupressure in addition to usual care in
      substance abuse treatment, which has been limited. DESIGN AND SETTING: This
      placebo-controlled pilot study was carried out in a community mental health
      center in a US-Mexico border city (Las Cruces) in southwestern New Mexico.
      PARTICIPANTS: A majority were Hispanic males with an average age of 32.8 years.
      Participants reported an average lifetime use of drug of choice of 14 years.
      INTERVENTION: In addition to usual care, participants received specific
      acupressure treatment and placebo acupressure treatment. The acupressure
      treatment was offered once a week for 6 consecutive weeks. MAIN OUTCOME MEASURES:
      The Hopkins Symptom Checklist (SCL-20) Depression Scale was administered before
      and after 6 weeks of treatment to assess changes in emotional distress. Brief
      Substance Craving Scale was used at baseline and weekly for 6 weeks to assess
      changes in craving. RESULTS: Both specific and placebo acupressure groups showed
      a significant reduction in craving at the end of treatment, with the specific
      acupressure group having a greater and more steady reduction in craving. Both
      specific acupressure and usual-care-only groups demonstrated a significant
      reduction in emotional stress. CONCLUSION: Overall, there was a positive response
      to the specific auricular acupressure treatment on psychological distress,
      craving, and drug/alcohol use measures. These encouraging preliminary results
      need to be duplicated in studies with larger sample sizes and longer treatment
      phases.

PMID- 16454150
TI  - David M. Eisenberg, MD: integrative medicine research pioneer. Interview by
      Karolyn A Gazella and Suzanne Snyder.

PMID- 16454151
TI  - [Avian flu: what kind of danger for public health?].

PMID- 16454152
TI  - [Hepatitis C in women planning a pregnancy: current opinions].
AB  - Chronic hepatitis C (VHC) is a worldwide public health issue. The mother-to-child
      transmission could be the main cause of hepatitis C infection in children.
      Despite the risk of histological injuries, chronic hepatitis C is not a contra
      indication to pregnancy. In patients with VHC, there is no evidence that the
      outcome could be modified. In co-infected patients (VIH-VHC), a caesarean should
      be proposed taking into account the significant risk of mother-to-child
      transmission. Breast-feeding is not contra-indicated. Systematic screening of
      VHC, discussed in this article, could be proposed in woman planning a pregnancy.

PMID- 16454153
TI  - [The quest of quality in the field of infectious disease at the hospital].
AB  - The implementation of a quality program in the field of the infectious diseases
      requires the prior definition of criteria (efficacy, low toxicity, low cost, less
      emergence of resistant strains) but also the target (the patient it-self, his or
      her community, the health system as a whole). A lot of tools are questioned:
      antimicrobial policy (escalation/streamlining, restricted formularies,
      antibiotics rotation), guidelines, relational tools (booklets and CME,
      prescription's formularies, computer's help and the Web) but also the role of an
      infectious diseases specialist and an antimicrobial management team. Finally, we
      outline some processes of evaluation.

PMID- 16454154
TI  - [Immunosuppressive agents in pediatric renal transplantation].
AB  - Advances in immunosuppressive therapy over the past decade have led to dramatic
      improvements of patient and graft survival. The immunosuppression that is used is
      constantly evolving. The goal remains to find the best combination that will
      optimize long-term graft survival, while minimizing the adverse effects. It is
      likely that in the near future the results will even be improved further by the
      development of new medications with a better therapeutic index and the induction
      of transplant tolerance.

PMID- 16454155
TI  - [Treatment of Paget's disease of bone with zoledronic acid].
AB  - Bone pain and bone deformities are the most common manifestations of Paget's
      disease of bone, even if the diagnosis is nowadays most often made by chance
      following a routine measurement of serum alkaline phosphatase. Woven bone is
      formed following a marked increase in bone resorption due to a stimulation of
      osteoclast activity. Biphosphonates constitute the modern treatment of Paget's
      disease of bone. Tiludronate (Skelid), or better risedronate (Actonel), are
      administered orally every day during at least 2 months. Zoledronic acid
      (Aclasta), as a single 15-min 5 mg infusion, has been recently compared to
      risedronate, 30 mg/d orally for 2 months, in two randomized studies including 357
      patients. Zoledronic acid had a superior therapeutic efficacy, as judged by its
      rapidity of action, the duration of the biochemical response and the percentage
      of responders. Thus, at 6 months, alkaline phosphatase levels were normalized in
      89% of the patients in the zoledronic acid group as compared to 58% in the
      risedronate group. The most frequent side effect was a flu-like syndrome,
      observed in 10% of the patients. An adequate intake of calcium and vitamin D is
      recommended to avoid posttreatment hypocalcemia. The introduction of Aclasta
      should simplify and improve the therapeutic management of Paget's disease of
      bone.

PMID- 16454156
TI  - [Prevention of preeclampsia: update].

PMID- 16454157
TI  - [Organization of obstetrical teaching and practice in our regions before 1815
      (first part)].
AB  - As elsewhere in Europe, the origins of Belgian obstetrics are related to the
      double rivalry between medical doctors and surgeons on the one hand and between
      surgeons and midwives on the other hand. Extension of obstetrical teaching in our
      regions has been hampered because of political turmoil resulting from the
      successive territorial dominations by Spain, Austria, France and Holland. In this
      evolution, the organisational sanitary model emerging from the French revolution
      exerted a prominent influence namely through creation of the subordinate grade of
      "Health Officer" and the suppression of local medical colleges as well as of the
      sole existing university faculty of medicine. These factors explain the poor
      quality of obstetrics which has prevailed on our soil until 1815.

PMID- 16454158
TI  - Inventions leading to the development of the diagnostic test kit industry--from
      the modern pregnancy test to the sandwich assays.
AB  - The universities are encouraged by the government nowadays to stimulate
      innovations and also to provide the proper machinery for assisting the protection
      and commercialisation of innovations. A better understanding of the innovation
      process may help to create an atmosphere suitable for inventions at the
      university. Examples can be taken from successful innovations previously made at
      the university. During the 1960's I made a series of inventions, which ultimately
      led to the development of the diagnostic test kit industry. The first, which I
      made as an undergraduate, was a simple and reliable test kit for diagnosis of
      pregnancy. This was followed by the solid phase radioimmunoassay and a solid
      phase assay for vitamin B12; next, the dual specific non-competitive sandwich
      assay and the in-vitro test for diagnosis of allergy, called RAST
      (Radioallergosorbent test). Organon in Holland with the pregnancy test kit, and
      Pharmacia in Sweden with test kits for radioimmunoassay, became pioneers among
      the diagnostic test kit industries. Pharmacia Diagnostics later became one of the
      leading diagnostic test kit companies in the world and has continued to be so in
      the field of allergy diagnosis. Each one of these inventions started with a few
      unique observations leading to a technical development. The pregnancy test as
      well as the allergy test emerged from the development of assay methods with
      unique qualities with the subsequent search for appropriate applications. The
      foreseeing of a commercial value on a future market was a very important step.
      This was followed by the search for a suitable industry interested to exploit the
      invention with its new business opportunity i.e. apply for a patent, produce and
      market the products, which in my case consisted of the necessary reagents and
      equipments for particular diagnostic tests. Finally, an agreement had to be
      settled between the entrepreneur and the inventors. This report describes these
      inventions and particularly discusses some crucial steps of the innovation
      processes.

PMID- 16454159
TI  - Acute glomerulonephritis associated with streptococcus pyogenes with concomitant
      spread of streptococcus constellatus in four rural families.
AB  - We studied history, renal histopathology and microbiology of an epidemic of acute
      glomerulonephritis associated with throat infections and uncommon culture results
      in four neighbour families. A 40-year-old man (index patient) was referred to a
      university hospital for dialysis and kidney biopsy due to a suspected acute
      glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin
      treatment had been started four days before the discovery of renal failure.
      Throat swabs were positive for beta-hemolytic streptococci, group C (GCS). GCS
      were also found in throat cultures from his wife and two of their children. The
      bacteria were typed as Streptococcus constellatus. A third child had S.
      constellatus expressing Lancefield antigen group G. A neighbour and two of his
      children fell ill the following week with renal involvement. Throat swabs from
      both these children were positive for S. constellatus. His third child had
      erythema multiforme and S. constellatus in the throat while a fourth child had
      beta-hemolytic streptococci group A; Streptococcus pyogenes. Kidney biopsies on
      the index patient and his neighbour showed an acute diffuse prolipherative
      glomerulonephritis compatible with acute post-streptococcal nephritis and
      microbiological analysis of renal tissue revealed in both cases S. pyogenes and
      S. constellatus. The families had had much contact and had consumed unpasteurized
      milk from our index patient's farm. In four of seven persons in two additional
      neighbouring families S. constellatus was found in throat swabs during the same
      month while two persons carried Streptococcus anginosus expressing the Lancefield
      C antigen. In conclusion spread of S. constellatus coincided with the occurrence
      of four cases of acute glomerulonephritis. The two biopsied patients had both S.
      pyogenes and S. constellatus present in renal tissue. The epidemic either
      suggested that the outbreak of glomerulonephritis was due to S. pyogenes but
      coincided with the transmission and colonization of S. constellatus or that the
      S. constellatus strains were highly pathogenic or nephritogenic and that this
      organism can be transmitted in such cases.

PMID- 16454160
TI  - Sertoli-Leydig cell tumour in a postmenopausal woman showing all facets of the
      insulin resistance syndrome (IRS).
AB  - Sertoli-Leydig cell tumours are rare sex stromal tumours with an incidence of <
      0.5% of all ovarian tumours. Most frequently this tumour occurs in young women
      with a history of amenorrhoea, hirsutism and lowered pitch. Here, we report on a
      woman with IRS, postmenopausal virilization and increased testosterone levels due
      to a Sertoli-Leydig cell tumour. This is the first case to suggest an association
      between IRS and Sertoli-Leydig cell tumours. Furthermore, we highlight the
      difficulties in detecting this ovarian tumour with sonography.

PMID- 16454161
TI  - Emergency operation for phlegmonous gastritis.
AB  - Phlegmonous gastritis is a rare inflammatory lesion in which bacterial infection
      occurs in the gastric wall. A case of phlegmonous gastritis producing an
      intramural filling defect in the stomach is presented. Endoscopy showed edematous
      and reddened gastric mucosa with a mass lesion in the gastric body and antrum. An
      abdominal CT scan showed diffuse and irregular thickening of the gastric wall. At
      emergency operation, a total gastrectomy with splenectomy was performed. The most
      important differential diagnosis is carcinoma, especially scirrhous-type gastric
      cancer. Radiographic findings of phlegmonous gastritis resemble those of
      scirrhous gastric cancer. More frequent recognition of this disease, early
      diagnosis and prompt institution of treatment is essential.

PMID- 16454162
TI  - Pyogenic liver abscesses secondary to carcinoma of the sigmoid colon: a case
      report and clinical features of 20 cases in Japan.
AB  - We report a case of liver abscesses associated with sigmoid colon cancer in an 81
      year-old woman. The patient was referred to our hospital because of a tumorous
      lesion of the sigmoid colon. Five days before the scheduled operation, she
      presented abdominal pain, fever and chill. Imaging scans revealed multiple liver
      abscesses in both lobes, which were successfully treated with intravenously
      administered antibiotics. Two weeks later, the patient underwent laparoscopic
      assisted sigmoidectomy. Nineteen cases of liver abscess associated with colonic
      cancer have been reported during the past ten years in Japan, and we report the
      clinical features of these cases in this paper. An aggressive search for the
      underlying cause of pyogenic liver abscess should be an integral part of the
      definitive treatment of this disease.

PMID- 16454163
TI  - Angiomyolipoma in the knee--a case report.
AB  - Extrarenal angiomyolipoma is an uncommon disease and this may be the first report
      of angiomyolipoma in the knee, mimicking a malignant sarcoma. A 38-year-old man
      without tuberous sclerosis presented with a history of increased mass in the knee
      joint. Computerized tomography and magnetic resonance imaging demonstrated a CS x
      CS x CR cm subcutaneous tumor in the knee joint. The tumor was widely excised.
      Histologically, the tumor was, well circumscribed, and composed of smooth muscle,
      vascular spaces, connective tissue, and mature fat. There were no signs of
      recurrence at one year and eight months after surgery.

PMID- 16454164
TI  - Desmoplastic melanoma arising in the ankle.
AB  - Desmoplastic melanoma (DM) is an uncommon but potentially devastating malignancy
      that can be cured with early recognition and surgery. DM often occurs in elderly
      men and develops on sun-exposed areas with the head and neck being the most
      common site of origin followed by the extremities and trunk. We report a rare
      case of DM occurring in the ankle in an 85-year-old woman. Magnetic resonance
      imaging of the affected ankle showed a 4.3 x 4.3 x 2.5 cm sized mass which was
      located in the subcutaneous region, attached to lower leg muscles, the fibula,
      and the calcaneus. No metastasis to the lung, liver, bones or abdominal lymph
      nodes was found. In spite of below knee amputation, the patient died of lung
      metastases 10 months after surgery. Among several factors causing early death of
      the patient, a large size, a deep location and rapid growth of the tumor seem to
      be most important.

PMID- 16454165
TI  - Lipofibromatosis arising in a pediatric forearm--a case report.
AB  - Lipofibromatosis is a rare pediatric tumour described by Fetsch et al. in 2000.
      There have been few reports about this tumour and few descriptions of its imaging
      features. We report a case of this tumour forming a slowly growing, painless mass
      arising in the forearm of a ten-month-old boy. This is the first report of
      lipofibromatosis to present the radiological findings before surgery. Plain
      radiography and computed tomography demonstrated a tumour located just beneath
      the fascia. Ultrasonic study showed a hyperechoic tumour of 33 x 30 x 7 mm in
      size. Magnetic resonance imaging demonstrated a multilobular mass with high
      signal intensities on both T1/T2 weighted images. Macroscopically, the tumour was
      poorly marginated. Microscopically, the tumour was composed of abundant adipose
      tissues transversed by fibroblastic bands. The adipose tissue occupied over 70%
      of the tumour. Adipocytes and fibroblastic element infiltrated into the normal
      skeletal muscle tissues. Recognition of this clinical entity is needed,
      especially in cases of lipomatous tumours arising in pediatric hands and feet.

PMID- 16454166
TI  - A low carbohydrate diet in type 1 diabetes: clinical experience--a brief report.
AB  - Due to failure to achieve control twenty-two patients with type 1 diabetes with
      symptomatic fluctuating blood glucose started on a diet limited to 70-90 g
      carbohydrates per day and were taught to match the insulin doses accordingly. The
      caloric requirements were covered by an increased intake of protein and fat. The
      purpose was to reduce the blood glucose fluctuations, the rate of hypoglycaemia
      and to improve HbA1c. After three and 12 months the rate of hypoglycaemia was
      significantly lowered from 2.9 +/- 2.0 to 0.2 +/- 0.3 and 0.5 +/- 0.5 episodes
      per week respectively. The HbAlc level was significantly lowered from 7.5 +/-
      0.9% to 6.4 +/- 0.7% after three months and was still after 12 months 6.4 +/-
      0.8%. The meal insulin requirements were reduced from 21.1 +/- 6.7 I.U./day to
      12.7 +/- 3.5 I.U./day and 12.4 +/- 2.6 I.U./day after three and 12 months
      respectively. Furthermore the triglyceride level was significantly lowered
      whereas the levels for total cholesterol and HDL-cholesterol were unchanged. The
      present report shows that a 70-90 g carbohydrate diet is a feasible long-term
      alternative in the treatment of type 1 diabetes and leads to improved glycaemic
      control.

PMID- 16454167
TI  - Who Expert Committee on Biological Standardization.

PMID- 16454168
TI  - [Toward nanotechnology--based regenerative medicine].

PMID- 16454169
TI  - [Nanotechnology in medicine].
AB  - Nanotechnology will play a key role in the post-genome sequencing era, since even
      revolutionary methods will be able to develop on a nanodevice, and it is
      applicable to the analysis of DNA, mRNA, protein, and other biomolecules. Recent
      progress in nanotechnology based on nanofabrication, nanocoating, and molecular
      nanotechnology is expanding the possibility of nanobiotechnology from genomics
      and proteomics to medical applications, including preventive medicine based on
      point-of-care test. Nanotechnology including quantum dot, photonic crystal, DNA
      chip as well as biodevice is applied to the analysis of genome network in some
      disease related cells. Genes related to important biological function of cell are
      identified by stimulating with different drugs and the genome networks for these
      cell reactions are predicted by computer software. Nanotechnology has been proved
      to be extremely important for future personalized medicine and systems biology.

PMID- 16454170
TI  - [Nano-engineering for biomedical applications].
AB  - Recently, medical applications of nanotechnology have received much attention.
      Among them, advances in polymer chemistry have significantly contributed to this
      field. Here, we review nano-engineering of functional polymers for diagnostic and
      therapeutic purposes, which have been carried out mainly by our group. Functional
      polymer-coated nanoparticles can be used for quick detection of biomarkers and
      DNA separation. Multiarray of hepatocyte spheroids on a microfabricated polymer
      brush surface can maintain the hepatocyte viability and liver-specific functions,
      offering a new high-throughput screening method of pharmacologically and
      toxicologically active compounds for drug discovery. Polymeric micelles are
      promising drug carriers, of which the critical parameters such as the size, drug
      loading and release can be controlled by engineering the constituent block
      copolymers. Thus, polymeric nano-device will be the leading technology in this
      field.

PMID- 16454171
TI  - [Creation of artificial cartilage by nanotechnology].
AB  - Artificial joints are made from hard and dry materials like metal or ceramics,
      although these artificial joints have several problems such as bacterial
      infection, high surface friction and wear, lack in shock-absorption. From this
      viewpoint, hydrogels have a high potential as substitutes for articular
      cartilage, although most of them suffer from lack of mechanical strength. In our
      recent study, we have found hydrogels, that exhibit high fracture strength as
      several tens of megapascals, extremely low coefficient of friction as 10(-4),
      high wear resistance, and with biocompatibility. These gels might open new era of
      soft and wet materials as substitutes for articular cartilage and other tissues.

PMID- 16454172
TI  - [Nanogel engineering and chaperone engineering].
AB  - Chaperone-like activity (to trap proteins in biomaterials without their
      aggregations and to control release of proteins in a native form) is important to
      design protein delivery systems as well as protein engineering. In general,
      irreversible adsorption of proteins is unavoidable in trapping them in hydrogel
      biomaterials because it is difficult to control the mesh size of the hydrogel
      matrix. We suggested that physically cross-linked nanogels with a size comparable
      to that of proteins are useful for these purposes. Tailor-made functional
      nanogels and hydrogels were designed by self-assembly of functional associating
      polysaccharides such as cholesterol-bearing pullulans. The nanogels can trap
      hydrophobic molecules, proteins and nucleic acids. They are useful as artificial
      molecular chaperones and also polymeric nanocarriers in DDS.

PMID- 16454173
TI  - [Discovery of silicon fullerene and its application to nanomedicine].
AB  - By ab initio supercomputer simulation highly symmetrical cage-structures of
      silicon with nanometer-sizes were predicted without any experimental parameters.
      These novel structures, which now are called silicon fullerenes have been
      produced experimentally following our theoretical predictions. Since silicon is
      manufactured with ultra-high purity and cheep in cost, and is safe for health,
      all of these facts make it possible to be used in medical applications. Some of
      these nanostructured materials have appropriate optical properties emitting
      strong visible light suitable for cancer detections with additional peptide which
      has antigen-antibody reaction. Presently we select CdSe nanoparticles for actual
      in vivo experiments which already commercialized, and successful results to
      detect the exact position of cancer for mouse from outside of the body have been
      obtained.

PMID- 16454174
TI  - [Nanoparticles prepared with PLA derivatives].
AB  - Chemical modification of poly (DL-lactic acid) (PLA) is very important to give it
      various functionalities. When hydrophilic moieties are combined to PLA, the
      products tend to form the nanoparticles with the hydrophilic moieties as their
      shell and PLA as a core in aqueous medium. The nanoparticles produced with such
      PLA derivatives are also expected to exhibit various functions physicochemically
      and physiologically. Further, they can work well as a valuable depot of
      biologically active reagents. In this section, the preparative procedure of PLA
      derivaties and several nanoparticles prepared with PLA derivatives are
      introduced. Moreover, the physicochemical and biopharmaceutical characteristics
      of the nanoparticles are overviewed.

PMID- 16454175
TI  - [Dendritic systems for drug delivery applications].
AB  - Dendrimers are synthetic, highly branched and nanometer-sized macromolecules that
      offer potential application to various fields. They have uniform size and
      molecular weight, wide internal cavity and modifiable surface functionality that
      made them very attractive for biological and drug delivery applications.
      Commercially available PAMAM (polyamidoamine) dendrimers are most frequently used
      for construction of delivery system by modification of surface amino groups. One
      of the examples is anticancer drug-PAMAM conjugate with folic acid (FA) for
      targeting. DNA linked FA-PAMAM and FITC-PAMAM conjugates have been recently
      developed. Polyester dendrimers are expected to be biodegradable and less toxic
      to cells. An example is shown. Lastly, construction of a delivery system using
      caged compounds for photochemical release of drug is described.

PMID- 16454176
TI  - [Carbon nanohorns as a novel drug carrier].
AB  - Carbon nanohorns are nanostructured spherical aggregates of graphitic tubes whose
      sizes are 80-100 nm in diameter. They have extensive surface area and don't need
      metal catalyst for their synthesis. The oxidization or acid treatment makes nano
      windows on their walls, through which distinct set of small molecules have been
      shown to infiltrate into their inner space. These unique properties of carbon
      nanohorns suggest the possible use of the nanomaterials as a novel carrier in
      drug delivery systems.

PMID- 16454177
TI  - [Development of nanomedicine using intracellular DDS].
AB  - In recent years, sustained release and targeting system using nanospheres or
      microspheres is noticed in systemic pharmacokinetics. However, in the near
      future, not only "systemic pharmacokinetics" but also "intracellular
      pharmacokinetics" seems to be important in Drug Delivery System research. In this
      context, we have tried to develop the novel cytoplasmic nanoparticle (NP)
      delivery methods using fusogenic liposomes (FL) and protein transduction domain
      (PTD). In this study, we demonstrated that the FL efficiently delivered the
      encapsulated NP to the cytoplasm directly in a fusion -dependent.
      Oligonucleotides attached to NP were gradually released in the cytoplasm after
      its efficient delivery using FL. Furthermore, we have succeeded in identifying
      the novel PTD using phage displayed random peptide library. In near future, this
      novel PTDs are applied to cytoplasmic NP delivery carrier. From these results, we
      suggested that this technology is very important to control the intracellular
      pharmacokinetics, and can be also applied to any NP which will be produced by the
      nanotechnology in the future.

PMID- 16454178
TI  - [Supramolecular nanocarrier for gene and siRNA delivery].
AB  - In this review article, supramolecular nanocarriers for gene and siRNA delivery
      were introduced. They were formed through the multimolecular assembly of block
      copolymers, containing the DNA or siRNA inside the core of the micelle structure.
      Due to the excellent stability under the physiological conditions, low toxic
      effect, and controllable gene functions, this system should be a promising
      candidate for in vivo therapeutic applications including the non-lethal diseases
      and the tissue engineering.

PMID- 16454179
TI  - [Envelope-type nano device for gene delivery].
AB  - We introduced a new concept "Programmed Packaging" for the rational development
      of non viral gene delivery system. There are many non-viral gene delivery system,
      however, their utility is limited in the in vitro experiments. The major reason
      is considered that it is difficult to package many functional devices into a
      nanoparticle. The new concept which we introduce here is named as Programmed
      Packaging, which is composed of the strategy to targeting, molecular design of
      functional devices to overcome barriers, and assembly technique to package them
      into a nanoparticle. In this article, we explain this concept and provide newly
      developed gene delivery systems based on this concept.

PMID- 16454180
TI  - [Gene delivery system responding to the intracellular signal].
AB  - We designed a peptide-polymer conjugate as a novel gene carrier, which could
      control gene-expression responding to intracellular cAMP-dependent protein kinase
      (PKA) or caspase-3 signal. Each polymer containing a substrate peptide (ALRRASLG
      for PKA or GGGDEVD GGRKKRRQRRRPPQ for caspase-3) could form a tight complex with
      plasmid DNA via electrostatic interaction, and in this state, the gene expression
      was totally suppressed. Once the grafted peptides become phosphorylated or
      hydrolyzed by the appropriate enzyme, the net charge of the peptide changes from
      cationic to neutral or anionic, respectively, and the polymer then releases the
      DNA, such that expression of the foreign gene should become activated. We expect
      that these systems can be applied to the novel highly cell specific gene delivery
      strategy.

PMID- 16454181
TI  - [Diagnosis of diseases by nanodevice].
AB  - I will describe the recent development of nanobiotechnologies based on the
      nanofabrication and molecular nanotechnology for diagnosis of diseases. The
      technologies allow us to develop novel methods to separate several biomolecules,
      including DNA, RNA, protein, peptide, polysaccharide, and glycoprotein towards
      the application in genomics, transcriptomics, proteomics, and glycoproteomics.
      The methods we have taken appear suitable for biomedical and clinical
      applications, including SNPs analysis, mutation analysis, haplotyping, DNA
      diagnosis, protein expression analysis, immunoassay, protein disease marker
      detection, point-of-care analysis, and future personalized medicine. The methods
      are also applicable to molecular imaging of cancer cell, cell diagnosis of
      cancer, and possible photodynamic therapy of cancer.

PMID- 16454182
TI  - [Development of polymeric nanoparticles-based vaccine].
AB  - Traditional vaccines are mainly composed of attenuated or heat-inactivated
      viruses. These vaccines often generate many unwanted side effects. Subunit
      protein and peptide vaccines are generally very safe vaccines with well-defined
      components. However, proteins and peptides are often poorly immunogenic and thus
      require the use of adjuvants to induce adequate immunity. Therefore, particulate
      adjuvants have been widely investigated in vaccine delivery systems. In
      particular, polymeric nanoparticles with entrapped antigens represent an exciting
      approach to control the release of vaccine antigens and optimize the desired
      immune response via selective targeting of antigen to professional antigen
      presenting cells. It is expected that biodegradable polymeric nanoparticles have
      great potential as carriers for systemic and mucosal vaccine delivery systems.

PMID- 16454183
TI  - [Super catalytic antibodies (antigenase) capable of destroying H. pylori urease].
AB  - Antigenase has an ability to decompose the antigen peptide or protein. We have
      produced some monoclonal antibodies(HpU mAbs series) for H. pylori urease. Out of
      them, the light chain of HpU-9 mAb possesses a catalytic triad composed of Asp,
      Ser and His, which acts as a catalytic site against the antigen, based on the
      structural analysis of molecular modeling. HpU-9-L belongs to the germline cs1
      which inherently encodes the catalytic triads in the sequence, indicating that
      HpU-9-L must be an antigenase. As expected, HpU-9-L showed the specific
      degradation against the beta-subunit of the urease. The heavy chain of HpU-2 also
      exhibited the specific degradation of the urease. These antigenases will be used
      for the medicinal application.

PMID- 16454185
TI  - [Insulin delivery by using PLGA nanoparticulate system].
AB  - The usefulness of PLGA nanoparticulate system for insulin delivery is described.
      The preparation methods of PLGA nanosphere encapsulating insulin are reviewed. To
      improve the therapeutic effect of insulin, the method of drug releasing control
      of PLGA nanosphere is discussed. The practical insulin DDS of PLGA nanosphere is
      summerized.

PMID- 16454184
TI  - [Nanotechnology for therapy of type 2 diabetes].
AB  - All-trans Retinoic Acid (atRA), is known as a member of retinoid, and the atRA
      nano-particle with coated by CaCO3 (nanoegg -atRA), was recently developed as a
      new drug delivery system (DDS). This nanoparticles stimulated insulin secretion
      from islets in a glucose-dependent manner at streptozotocin (STZ)-induced
      diabetes. The stains on pancreas of Wistar rat at STZ induced diabetes, which was
      subcutaneous administered nanoegg -atRA 6 mg/head/week for 141 days, showed not
      only the expression of PDX-1 but also the presence of beta cell in islet of
      Langerhans. Furthermore, the increase of insulin concentration in plasma was also
      observed. Our data indicate that nanoegg -atRA might contribute to the
      regeneration of beta cells in vivo, and provide useful information for future
      therapy of diabetes mellitus.

PMID- 16454186
TI  - [Application of nanotechnology to hemodialysis membrane].
AB  - Almost forty years have passed from the start of hemodialysis therapy in Japan. A
      lot of numbers of dialysis patient have received the benefits from this therapy.
      In hemodialysis therapy, effective removal of uremic toxins and biocompatibility
      are required. Hemodialysis membrane plays the most important roles to achieve
      these requirements. Removal of uremic toxins and biocompatibility are influenced
      by solute permeability through hemodialysis membrane and characteristics of
      hemodialysis membrane surface keeping in contact with blood. This paper
      summarized nanostructure of hemodialysis membrane made from polysulfone adding
      polyvinylpyrrolidone from some reports, and process of membrane formation from
      polymer solution. Solute permeability has relation to pore size penetrating
      hemodialysis membrane, and biocompatibility has relation to swell of polymer
      particles on surface of hemodialysis membrane immersed in water.

PMID- 16454187
TI  - [Micelle carrier system in clinical trial].
AB  - The problems of cytotoxic agents have been attributed to their low therapeutic
      indices and limited efficacy due to the non selective nature of their molecular
      targets and their inability to accumulate selectively in cancer tissue. Passive
      targeting is based on the so-called enhanced permeability and retention (EPR)
      effect. To use the EPR effect to full advantage, several techniques have been
      developed, namely, modification of the structures of drugs and development of
      drug carriers. In this review article, the results of preclinical and clinical
      studies of doxorubicin-incorporating immunoliposome, MCC-465 and micelle -forming
      polymeric drugs such as doxorubicin-incorporating micelle, NK911 and taxol
      incorpolating micelle, NK105.

PMID- 16454188
TI  - [Spicamycin derivative].
AB  - Spicamycin, induced differentiation of human myeloid leukemia cells (HL-60), is
      found to show a potent antitumor activity by inhibiting protein synthesis. Among
      the various semisynthetic derivatives of spicamycin, KRN5500 showed a marked
      efficacy in human tumor xenograft model. KRN5500 itself has, however, only minor
      inhibitory effects on protein synthesis in cell free system. A metabolite, SAN
      Gly, which is thought to be generated through metabolism of KRN5500 by a
      cytosomal enzyme, exhibited a marked inhibitory effect. KRN5500 is expected to be
      useful even for treatment of refractory solid tumors because of its unique
      antitumor mechanism. A phase I clinical trials underwent at the National Cancer
      Center Hospital in Tokyo and at the National Cancer Institute in the USA.
      Unfortunately, the drug toxicities in addition to grade 4 pulmonary disorders
      were occurred, partly caused by the organic solvents and chemical essential for
      its dissolution. To overcome such a severe adverse effects, we conducted to
      examine whether incorporation of KRN5500 into polymeric micelles (KRN/m) could
      reduce a pulmonary disorder using a bleomycin (BLM)-induced lung injury rat model
      or exhibit antitumor activity similar to KRN5500. In conclusion, this study
      demonstrated that KRN/m is superior to KRN5500 because the pulmonary toxicity was
      reduced and the potent antitumor activity of KRN5500 was retained after the
      incorporation of KRN5500 into micelles. We think that these results justify a
      clinical phase I trial of KRN/m.

PMID- 16454190
TI  - [Nanotechnology-based regenerative medicine--cell sheet engineering utilizing
      temperature-responsive culture dishes].
AB  - Regenerative medicine is believed to overcome shortcomings of conventional
      therapies including symptomatic drug therapy and surgical removal. We have
      utilized nanotechnology for regenerative medicine to develop temperature
      responsive culture dishes, on which a temperature-responsive polymer is
      covalently grafted with precise control of its density and thickness in a
      nanometer scale. Confluent cells cultured on the dishes are intactly harvested as
      a single contiguous cell sheet by reducing temperature below 32 degrees C, and
      harvested cell sheets are subjected to tissue reconstruction, named cell sheet
      engineering. Here, we introduce the examples of clinical applications including
      corneal regeneration as well as large animal studies.

PMID- 16454189
TI  - [Corticosteroid-loading PLA/PLGA-nanospheres].
AB  - We developed nanospheres for the intravenous injection that have had sustained
      release and targeting to the efficiently anti-inflammation effect. These
      nanospheres formed by poly(D,L-lactic/glycolic acid) (PLGA) or poly(D,L-lactic
      acid) (PLA), biodegradability and biocompatibility polymer, that were
      encapsulated betamethasone phosphate and zinc. Result of experimental
      inflammation models shown that there nanospheres increased effect by targeting to
      inflammatory sites and also promoted sustained release of betamethasone phosphate
      from the nanospheres. Moreover, the effect of nanospheres were stronger than
      clinical pharmaceutical preparation. We propose that these nanospheres are the
      pharmaceutical preparation to have efficient powerful inflammation action.

PMID- 16454191
TI  - [Regenerative therapy for damaged heart].
AB  - Regeneration therapy has currently emerged as one of the promising treatments for
      the patients suffering from severe heart dysfunction. Direct transplantation of
      isolated myoblasts or bone marrow mononuclear cells, and recruitment of stem
      cells from bone marrow by G-CSF administration have been already clinically
      performed. As further advanced therapy, research on fabricating three-dimensional
      (3-D) cardiac grafts by tissue engineering technology has also now begun. Most
      popular approach of tissue engineering is using 3-D biodegradable scaffolds as
      alternatives of extracellular matrix. By contrast, we have successfully
      fabricated macroscopically beating myocardial tissue by layering cell sheets
      which are harvested from intelligent culture dishes grafted with temperature
      responsive polymer in nano-scale. These regenerative medicines should rescue many
      patients.

PMID- 16454192
TI  - [Medical nanodevices].
AB  - Development of implantable medical nanodevices enables us continuous automatic
      treatment of patients from inside of their body. Bionic devices, interfacing with
      neural systems and substituting native functions, such as bionic pacemaker,
      bionic pressure controller are candidates to miniaturize. For such
      miniaturization, efforts to reduce size of power supply (e.g., biological fuel
      cell) and to establish reliable high-throughput, low power telecommunication
      (e.g., spread spectrum telecommunication) are required. Simple devices such as
      pacemakers would benefit from miniaturization by lowering invasion and by
      developing a new usage such as ventricular resynchronization.

PMID- 16454193
TI  - [The development of magnetically operated microforceps and microendoscopes].
AB  - In minimally-invasive intraluminal diagnosis or treatment, catheters or
      endoscopes need a high degree of operator ability for guidance to appropriate
      routes, especially in small peripheral regions. Movable microstructures and
      assistant guiding technolgies should be developed to make these procedures
      easier. The use of magnetism, which can give force to simple internal objects
      safely with no contact, is a possible option. To facilitate the realization of
      magnetic operation in clinical medicine, magnetically operated microforceps which
      assist endoscopic submucosal dissections in the stomach have been developed, and
      are being tested in clinical trials. As a next step, flexible microendoscopes
      which can be guided by magnetic force are being developed. Automated magnetic
      guidance is also being developed for future assistance in intraluminal
      procedures.

PMID- 16454194
TI  - [Nano -level imaging for analyzing protein structure and function].
AB  - The present manuscript outlines the nano-level imaging project, which is under
      promotion by the three national research institutes and supported by a research
      grant from the Ministry of Health, Labor and Welfare (nano-001). This research
      project targets collecting fundamental information regarding comprehensive
      understanding of cardiovascular, neurological and the other disorders, developing
      new diagnostic and therapeutic methods by visualizing protein structure and
      function in atomic(sub-nano level) or molecular (nano-level) resolution. The
      results of the current projects will be extended into drug design, clinical
      diagnostic technology and medical materials in near future.

PMID- 16454195
TI  - [Computer supporting system of neurological topodiagnosis].
AB  - Neurological topodiagnosis has some considerable difficulties because of the
      complex anatomy involved. One answer to this problem is making a computer system
      able to map the pathways responsible for the patients' symptoms and also able to
      pinpoint the causative lesions. We introduced a new computer system for such
      purpose. Human memory has its limits so it is in a way inevitable that computers
      will be used in neurological diagnosis.

PMID- 16454196
TI  - [Application of anti-resorptive drugs for the treatment of osteoporosis].
AB  - The applications of anti-resorptive drugs for the treatment of osteoporosis were
      reviewed. The aging, low bone mineral density, increased bone turnover, and
      prevalent fracture were risk factors for new fracture. Bisphosphonates
      (alendronate and risedronate) and raloxifene showed a significant reduction in
      relative risk for vertebral fractures. On the other hand, alendronate and
      risedronate were the only two therapies that had a significant pooled treatment
      effects on nonvertebral fracture reduction. Hip fractures in Japan increase in
      the age of 70 years and over. This etiology indicates that bisphosphonate might
      be suitable for the patients who were 70 years of age and over. There was no
      significant difference between alendronate and risedronate in the efficacy of the
      decrease of bone resorption marker.

PMID- 16454197
TI  - [Annulated heterocycles from methyl 6-chloro-5-formyl-2-methyl-4-(2-nitrophenyl)
      1,4-dihydropyridine-3-carboxylate].
AB  - The pyridone 1a reacts with POCl3/DMF to yield the title compound 2a. After
      irradiation of 2a the enolether 3 is isolated, as shown by an X-ray structure
      determination. The pyridine 4 obtained by dehydrogenation of 2a leads under
      reductive conditions to the benzo[c][2,7]naphthyridines 5-7. The reaction of 4
      with o-phenylenediamine gives the benzimidazole 8, while using 2-aminophenol or 2
      aminothiophene respectively the pyrido[2,3-b[1,5]benzoxazepine 11 and the
      corresponding benzothiazepine 12 are obtained.

PMID- 16454198
TI  - A novel cationic cardiolipin analogue for gene delivery.
AB  - The optically active R and S isomers of cationic cardiolipin analogues (CCA) were
      synthesized and evaluated as a liposome based transfection reagent. Both isomers
      form stable liposomes with mean diameters of about 120 nm without any additional
      lipid ingredients. No significant change in particle size distribution profile
      was observed over one-month storage at room temperature (20-25 degrees C). The
      gel to liquid crystalline phase transition temperature (Tm) of cationic liposomes
      comprised of both R and S isomers was approximately 2 degrees C, as measured by
      differential scanning calorimetry (DSC). Both isomers also formed stable
      liposomes when combined with DOPE. In vitro transfection efficiency of the
      CCA/DOPE liposomes complexed to plasmid DNA was evaluated using a luciferase
      reporter gene. Both liposomes composed of R and S isomers of the cationic
      cardiolipin displayed higher transfection efficiency than commercially available
      Lipofectin. Further in vivo studies are warranted.

PMID- 16454199
TI  - A convenient TLC method for the identification of local anesthetics.
AB  - A TLC method for the separation of seven local anesthetics and the related
      antiarrhythmic drug procainamide was developed. Spraying the plates with
      cobalt(II) thiocyanate solution, followed by spraying with Ehrlich's reagent
      allowed a clear distinction between the drugs, except for the couple
      articaine/prilocaine. Articaine could be distinguishedfrom prilocaine and other
      local anesthetics by a colour reaction with copper(II) sulphate solution.

PMID- 16454200
TI  - HPLC assay and pharmacokinetic study of atorvastatin in beagle dogs after oral
      administration of atorvastatin self-microemulsifying drug delivery system.
AB  - A specific and accurate reversed-phase HPLC with UV detection was developed for
      the assay of atorvastatin in beagle dog plasma. Indomethacin was used as the
      internal standard. Atorvastatin was extracted by protein precipitation, the
      extracts were injected into a Kromasil C8 column (150 mm x 4.6 mm, 5 microm) with
      UV wavelength set at 270 nm. The mobile phase consisted of acetonitrile:0.1 mol/L
      ammonium acetate buffer (pH 4.0) (65:35% v/v) at a flow rate of 1.0 ml/min. The
      column was at ambient temperature (25 degrees C). The injection volume was 25
      microl. The blank plasma did not interfere with the determination of atorvastatin
      and indomethacin. A good linear relationship was obtained between the peak area
      ratio of atorvastatin to indomethacin and the concentration of atorvastatin over
      the range of 0.05 to 2.5 microg/mL. The limit of quantification was 25 ng/mL, the
      limit of detection was 8 ng/ml. The total chromatographic analysis time was
      within 9 min. The method is accurate, precise and fast for the assay of
      atorvastatin in plasma following oral administration of an atorvastatin SMEDDS to
      healthy beagle dogs.

PMID- 16454201
TI  - Compatibility and stability of the novel anticancer agent ES-285 x HCl formulated
      with 2-hydroxypropyl-beta-cyclodextrin in infusion devices.
AB  - ES-285 x HCl is a novel marine-derived anticancer agent isolated from the clam
      Spisula polynyma. The compound is pharmaceutically formulated as a lyophilised
      product containing 25 or 50 mg ES-285 x HCl and 500 or 1000 mg 2-hydroxypropyl
      beta-cyclodextrin per dosage unit and requires reconstitution with sterile water
      for injection before intravenous administration. The aim of this study was to
      determine the stability and compatibility of ES-285 x HCl in infusion devices. ES
      285 x HCl was shown to be stable at concentrations of 10-1400 microg/ml after
      dilution in 5% dextrose in water and compatible with PE infusion containers and
      PE and silicone tubing. No sorption on- or into the administration set was
      observed at concentrations equal to or above 20 microg/ml. In conclusion, ES-285
      x HCl infusion solutions can be administered without stability or sorption
      problems using a PE infusion container and PE or silicone tubing in
      concentrations equal or above 20 microg/ml in 3-hour or 24-hour infusion
      administration schedules.

PMID- 16454202
TI  - Biodegradable periodontal intrapocket device containing metronidazole and
      amoxycillin: formulation and characterisation.
AB  - The purpose of the study was to formulate biodegradable intrapocket dental films,
      which could be easily placed into the periodontal pocket, and be capable of
      delivering therapeutic concentrations of amoxycillin and metronidazole for
      prolonged period of time with a much lower dose, hence obviating untoward side
      effects. A biodegradable intrapocket device containing amoxycillin and
      metronidazole was prepared using 69.29 mg each of amoxycillin and metronidazole,
      2.0% diethyl phthalate plasticizer and 750 mg poly (L-lactide-co-glycolide). The
      device was optimized on the basis of evaluation parameters such as weight
      variation, content uniformity, surface pH, and in vitro and in vivo release
      studies. The films showed sustained in vitro release for a period of 16 days. In
      vivo release studies showed that drug concentrations were maintained above the
      MIC value for the entire period of the release studies. The samples from this
      study were capable of inhibiting the growth of most test strains. The combination
      of amoxycillin and metronidazole in the carrier polymer poly (L-lactide-co
      glycolide) not only showed an extended spectrum of antimicrobial activity but
      also showed a synergistic effect against E. limosum, which had been reported the
      resistant to metronidazole in earlier studies. Stability studies were conducted
      on the optimized formulation and the degradation rate constant was found to be
      4.6 x 10(-4)/day for metronidazole and 4.8 x 10-4)/day for amoxycillin. The drug
      was released locally and had a high benefit to low risk ratio as compared to
      systemic administration which is unacceptable due to, low benefit to high-risk
      ratio. Hence low-dose site-specific films present a better alternative.

PMID- 16454203
TI  - Measurement of diffusion through calcium alginate gel matrices.
AB  - The diffusion of high molecular weight dextran samples and low molecular weight
      quinine sulphate in homogenous calcium alginate gel matrices was studied. An
      experimental design suitable for studying the diffusion of substances from or
      through a gel sample was established. The experimental results indicate that the
      different types of molecules diffuse in the gel by different mechanisms. The
      diffusion rate of the molecules in the gel is dependent on gel composition.

PMID- 16454204
TI  - Correlation between in vitro release from topical delivery vehicles and
      microbicidal activity of triclosan.
AB  - This study reports the formulation, stability, in vitro release and microbicidal
      activity of a cream, emulsion, foot gel, cover stick and after sun spray
      containing triclosan. Triclosan is a broad-spectrum antimicrobial agent with
      activity against a wide range of both gram-negative and gram-positive bacteria
      that has found increasing popular use in personal care products. These products
      were stable for up to 3 months when stored at 5, 25, and 40 degrees C.
      Antimicrobial zone inhibition tests showed that that was a liner relationship, R2
      > 0.92, between the release of triclosan from these products and the size of the
      inhibition zones. This means the in vitro/in vivo correlation for these products
      was good and that release studies can be used to predict the antimicrobial
      activity of triclosan.

PMID- 16454206
TI  - Effect of nerodilol, carvone and anethole on the in vitro transdermal delivery of
      selegiline hydrochloride.
AB  - The aim of the study was to investigate the effect of terpene enhancers
      (nerodilol, carvone or anethole) on the in vitro transdermal delivery of
      selegiline hydrochloride with a broad objective of developing a membrane
      moderated transdermal therapeutic system (TTS). The in vitro permeation studies
      were carried across the rat epidermis from hydroxypropyl methylcellulose (HPMC)
      gel drug reservoir containing selected concentrations of nerodilol, carvone or
      anethole and selegiline hydrochloride. The amount of selegiline hydrochloride
      permeated during the 24 h of the study (Q24) from HPMC gel drug reservoir without
      terpene enhancer was 2169 +/- 50 microg/cm2 and the corresponding flux of the
      drug was 92 +/- 1 microg/cm2 x h. The amount of drug permeated and its flux
      increased with an increase in terpne concentration in HPMC gel drug reservoir.
      Nerodilol provided an approximately 3.2-fold increase in the flux of selegiline
      hydrochloride followed by carvone with a 2.8-fold increase, and anethole with a
      2.6-fold increase. It is concluded that the terpene nerodilol, carvone and
      anethole produced a marked penetration enhancing effect on the in vitro
      transdermal delivery of selegiline hydrochloride that could possibly be used in
      the formulation of membrane-moderated TTS.

PMID- 16454205
TI  - Influence of complexation with cyclodextrins on photo-induced free radical
      production by the common sunscreen agents octyl-dimethylaminobenzoate and octyl
      methoxycinnamate.
AB  - The influence of complexation with hydroxypropyl-beta-cyclodextrin (HP-beta-CD)
      or beta-cyclodextrin (beta-CD) on the photo-induced production of free radicals
      by the sunscreen agents octyl-dimethylaminobenzoate (ODAB), oxybenzone (OB) and
      octyl-methoxycinnamate (OMC) was investigated. The formation of radical species
      during irradiation was detected by spin-trapping electron paramagnetic resonance
      (EPR) spectroscopy. 2,2,6,6-tetramethylpiperidine-1-oxyl, nitroxide radical
      (TEMPO) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were used a spin-traps.
      Following the 4-h illumination with simulated sunlight, OB did not generate
      radicals. On the other hand, photoexcitation of solutions containing ODAB or OMC
      produced a marked decrease (>40%) of the TEMPO signal intensity, demonstrating
      the formation of carbon-centred radicals. In addition, the results obtained on
      irradiation of ODAB solutions containing DMPO as spin-trap indicated the
      generation of oxygen-centred radicals. Complexation of ODAB with HP-beta-CD and
      OMC with beta-CD markedly inhibited (>64%) the formation of free radicals
      generated by the sunscreens on exposure to simulated sunlight. Therefore,
      inclusion of ODAB and OMC into the cyclodextrin cavities minimizes their
      photosensitising potential.

PMID- 16454207
TI  - Furoxan derivatives as cytotoxic agents: preliminary in vivo antitumoral activity
      studies.
AB  - Furoxan derivatives with in vitro cytotoxic activity were investigated as
      antitumoral agents in vivo. The compounds were tested in murine models of both
      CCRFS-180 II sarcoma and mammary adenocarcinoma. Two of the furoxan derivatives
      considered here, 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide and 3-carbonitrile-4
      phenyl-1,2,5-oxadiazole N2-oxide, present in vivo antitumoral activity. They were
      able to produce more than 90% of tumoral necrosis under the experimental protocol
      of administration and posology employed. NO-releasing capacity of furoxans may
      explain the anti-neoplastic activity of these compounds.

PMID- 16454208
TI  - Interaction between venlafaxine and caffeine on antinociception in mice.
AB  - This study was conducted in order to evaluate whether or not caffeine has any
      effect on venlafaxine antinociception in mice in acute application. Swiss albino
      mice, both male and female, were tested with hot plate analgesiameter set at 52.5
      +/- 0.1 degrees C. The mice were divided into four groups receiving saline +
      saline, caffeine (5 mg/kg) + saline, saline + venlafaxine (70 mg/kg) and caffeine
      (5 mg/kg) + venlafaxine (70 mg/kg) intraperitoneally. Each animal was tested on
      hot plate before treatment and 30, 45, 60 min after injections. Venlafaxine
      produced a significant antinociceptive effect at 30 and 45 min and the effect
      decreased at 60 min. Caffeine alone showed no significant antinociceptive effect
      at the applied dose however, it significantly antagonized the antinociceptive
      effect of venlafaxine at 30 min. As a result, caffeine inhibits the
      antinociceptive effect of venlafaxine in acute application in mice and this
      observation provides new evidence that the adenosinergic system may play a
      significant role in the mechanism of antinociceptive action of venlafaxine. This
      study raises the possibility that caffeine consumption might influence the
      effectiveness of venlafaxine in the treatment of pain in humans.

PMID- 16454209
TI  - Antimalarial activity of methylpiperazinyl-substituted benzophenone-based
      farnesyltransferase inhibitors.

PMID- 16454210
TI  - Effect of Epilobium angustifolium L. extracts and polyphenols on cell
      proliferation and neutral endopeptidase activity in selected cell lines.
AB  - The ability of Epilobium extracts and polyphenols to induce neutral endopeptidase
      (NEP) activity and to inhibit the proliferation in cell lines with high NEP
      expression (SK-N-SH) and with low NEP expression (PC-3) was investigated.
      Epilobium extracts enhanced in a dose-depend manner NEP activity in both cell
      lines with additional inhibition of cell proliferation. The sensitivity of cells
      depended on basal enzyme activity. SK-N-SK cells were much more sensitive than PC
      3 cells. Oenothein B enhanced NEP activity at a concentration of 5-40 microM
      while quercetin-3-glucuronide and quercetin-3-O-(6"-gal-loyl) galactoside showed
      slight or no activity at a concentration of 100 microM. The comparison of
      activities of the extracts with oenothein B, a dimeric macrocyclic ellagitannin,
      suggests that the latter is mostly responsible for the observed effects. Taking
      into account the role of NEP in the homeostasis of signalling peptides, Epilobium
      angustifolium extracts may be a potential herbal remedy in diseases connected
      with the disturbed metabolism of signaling peptides caused by an unbalanced
      neutral endopeptidase activity.

PMID- 16454211
TI  - Triterpenoids from pyrethrum tatsienense.
AB  - Two novel and eight known triterpenoids were isolated from alcoholic extract of
      the whole plant of Pyrethrum tatsienense. The structures of new compounds were
      elucidated as olean-12-en-3beta,11alpha,16beta-triol-3-O-palmitate (1), ursa-12
      en-3beta,11beta,16beta-triol-3-O-palmitate (2) by spectroscopic methods including
      intensive 2D NMR techniques (H1-H1 COSY, gHMQC, gHMBC) and FAB-MS, and the known
      compounds were identified on the basis of comparing their NMR data with those of
      corresponding compounds in the literature.

PMID- 16454212
TI  - Colour reactions of griseofulvin Ph. Eur. 2005 using hydrogen peroxide solution
      or bromate or iodate as oxidant instead of potassium dichromate.

PMID- 16454213
TI  - N-octyl-beta-thioglucoside enhances the transdermal permeation of ketotifen.

PMID- 16454214
TI  - New prenylated flavones from Pongamia pinnata.

PMID- 16454215
TI  - Reproductive performance of pregnant rats and embryotoxic effects of
      ciprofloxacin.

PMID- 16454216
TI  - Cytotoxic chemotherapy in advanced non-small cell lung cancer.

PMID- 16454218
TI  - Inhaled foreign bodies in adolescents and adults.
AB  - BACKGROUND: Accidental foreign body inhalation is not uncommon. The incidence is
      high in children, especially the very young ones. We evaluated the management of
      inhaled foreign bodies in an adult respiratory medical unit, highlighting
      circumstances leading to inhalation, associated complications and difficulties
      encountered at bronchoscopic retrieval. METHODS: We reviewed all cases of inhaled
      foreign bodies presenting over a period of 12 years (1991-2003). RESULTS: 5 of 8
      cases were teenagers whereas 3 were aged over 55 years. The older patients had co
      morbidities and had aspirated food particles. In 2 cases, a bronchoscopy was
      performed primarily to exclude lung cancer, and the discovery of a foreign body
      was a surprise. Pulmonary complications related to foreign body inhalation were
      common among this group. All 5 teenage patients presented after inhalation of
      small objects. 4 patients from the teenage group had general anaesthesia; in 2 of
      them a laryngeal mask airway was employed, whilst 2 had endotracheal intubation.
      Only one patient was given a rigid bronchoscopy following failure of the
      fiberoptic instrument. Difficulties at retrieval of foreign body were frequently
      encountered. CONCLUSIONS: In the adolescent and adult patients, most inhaled
      foreign bodies are retrievable by flexible bronchoscopy. However, facilities for
      rigid bronchoscopy should be available as a back-up. Pulmonary complications are
      common after foreign body inhalation especially in the older patients.
      Difficulties at bronchoscopic removal may occur due to late presentation or to
      the site and/or position of the foreign body within the tracheobronchial tree.

PMID- 16454217
TI  - Mitomycin, ifosfamide, cisplatin for non-small cell lung cancer: an
      implementation study.
AB  - BACKGROUND: The MIP regimen (mitomycin, ifosfamide, cisplatin) demonstrated its
      effectiveness as first-line chemotherapy in phase II and III trials in NSCLC. We
      aimed to determine whether these results could be confirmed in a hospital
      population. METHODS: Between 1987 and 2004, 204 patients with NSCLC received MIP
      in our institution. Patients treated in and off trials received the same
      combination of cisplatin (50 mg/m2), ifosfamide (3 g/m2) and mitomycin C (6
      mg/m2) every three weeks and were staged and followed in a similar way. RESULTS:
      Response rates for patients treated in or outside trials were 36.8% and 40.7%,
      respectively. After multiple logistic regressions, the only statistically
      significant factor predicting objective response was stage. The median survival
      time was 54.6 and 43.7 weeks respectively for patients treated in and outside
      trials. In multivariate analysis, four factors were statistically significantly
      associated with better survival: good performance status (p = 0.003), normal LDH
      value (p < 0.001), early stage (p = 0.01) and active smoking (p = 0.03).
      CONCLUSION: Participation in a clinical trial was not associated with a
      significant difference in efficacy. This implementation study thus confirms the
      activity of the MIP regimen when used in the routine management of patients with
      NSCLC.

PMID- 16454219
TI  - Impact of children's respiratory allergies on caregivers.
AB  - BACKGROUND: Despite the great attention that has been paid to HRQoL in children
      with respiratory allergy, few studies have addressed this aspect in relation to
      caregivers. The aim of our study was to evaluate the impact of childhood
      respiratory allergies on caregivers by means of a new method. METHODS: 119
      parents of children suffering from allergies (75 suffering from asthma and 44
      suffering from rhinitis) were recruited from three Italian Allergy Units. Parents
      were asked to complete the Disease Impact On Caregiver (DIOC), a new non disease
      specific questionnaire, validated on the Italian population. The questionnaire
      consists of 31 items grouped in four factors (Performance, Personal
      gratification, Psychophysical endurance, Socio-emotional domain) and covers the
      life aspects that could be affected by the assistance duties towards an ill
      family member. RESULTS: Child's asthma resulted to have a worse impact on many
      aspects of a parents' life than rhinitis. Differences resulted to be
      statistically significant in 19 aspects out of the 31 assessed. The worse impact
      of asthma versus rhinitis was confirmed in the following domains: Performance
      (24.0 +/- 18.2 vs 11.5 +/- 17.8), Personal gratification (26.3 +/- 20.5 vs 12.1
      +/- 16.5) and Psychophysical endurance (35.0 +/- 24.8 vs 18.8 +/- 21.7). In the
      Socio-emotional domain no difference emerged. CONCLUSIONS: Compared to parents of
      rhinitics, parents of asthmatic children appear to be more compromised in their
      resistance to stress, mood, emotional stability, amount of spare time and leisure
      activities. Our results suggest the need of giving the due attention to these
      problems both in clinical practice and in research, in order to avoid possible
      interferences of the caregiver's distress in the optimization of treatment
      outcome.

PMID- 16454220
TI  - Current management of spontaneous pneumothorax.
AB  - Spontaneous pneumothorax is divided into primary, when there is no underlying
      lung disease, and secondary, mainly caused by chronic obstructive pulmonary
      disease. A variety of different non-invasive and invasive treatment options
      exist. Due to the lack of large randomised controlled trials no level A evidence
      is present. A first episode of a primary spontaneous pneumothorax is treated by
      observation if it is < 20% or by simple aspiration if it is > 20%, but
      recurrences are frequent. For recurrent or persisting pneumothorax a more
      invasive approach is indicated whereby video-assisted thoracic surgery provides a
      treatment of lung (resection of blebs or bullae) and pleura (pleurectomy or
      abrasion). In patients with a secondary spontaneous pneumothorax related to
      chronic obstructive pulmonary disease, there is an associated increased mortality
      and a more aggressive approach is warranted consisting of initial thoracic
      drainage followed by recurrence prevention by thoracoscopy or thoracotomy in
      patients with a low or moderate operative risk. Talc instillation by the thoracic
      drain is preferred for patients with a high operative risk.

PMID- 16454221
TI  - COPD and tobacco smoke.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammation of the
      airways, including the parenchyma and the pulmonary vasculature. The burden of
      COPD is increasing around the world in terms of morbidity and mortality in adult
      population. Active smoking is a major risk factor for COPD, although there is
      individual susceptibility to the effects of tobacco smoke. This variability could
      result from host as well as environmental factors. Even passive smoking in early
      childhood as well as intrauterine exposure could pave the way for COPD. Tobacco
      smoke induces a specific, persistent inflammation, different from that of asthma.
      Three other processes accompany and interact with inflammation: imbalance of both
      the proteases-antiproteases, the oxidants-antioxidants, and improper repair
      mechanisms. These processes respectively lead to mucus hypersecretion and alveol
      wall destruction, dysfunction and death of biological molecules, damage to the
      extracellular matrix and pulmonary fibrosis with adventitial, submucosal and
      smooth muscle thickening. The earlier the smoke exposure, the greater the level
      of decline in lung function. Combined mucus hypersecretion, reduced clearance,
      and impairment of the lung defence mechanisms explain why COPD patients even with
      stable condition, carry potential respiratory pathogens in significant
      concentration, paving the way for infection and acute exacerbations of COPD.
      Every additional exacerbation in a smoker deteriorate more the lung function.
      Fortunately, smoking cessation, which is a part of the respiratory rehabilitation
      could reduce the number of hospitalisations and the decline of lung function, and
      thus reduce the management cost of the disease and improve the quality of life.
      The earlier the quitting, the better the improvement of FEV1. "Smoking cessation
      is the single effective and cost effective way to reduce exposure to COPD risk
      factors" (GOLD, evidence A).

PMID- 16454222
TI  - Constrictive bronchiolitis obliterans in patient with Castelman's disease.
AB  - A 37-year-old woman with hialin- vascular type Castelman's disease (CD) localised
      in the retroperitoneal region, incompletely resected, developed progressive
      dyspnoea. The chest radiograph taken 3 months before the operation was normal.
      The chest CT scan revealed diffused bronchiectases, hyperinflation and air
      trapping. Pulmonary function tests disclosed severe obstructive impairment with
      hyperinflation. The bronchoscopic examination of the bronchial tree was normal.
      Cultures of sputum, bronchial washing and blood were negative. No pemphigus
      antibodies were found. Mycoplasmal, chlamydial and viral infections were
      excluded. Histological examination of specimens obtained by open lung biopsy
      revealed bronchiolar inflammation, submucosal bronchial fibrosis with
      obliteration of bronchiolar lumen. Constrictive bronchiolitis obliterans (CBO)
      was diagnosed. Despite slight clinical and spirometric improvements that were
      achieved due to corticosteroid therapy, one year later she died as a result of
      respiratory failure. It is widely known that patients with CD develop CBO during
      the course of paraneoplastic pemphigus. However we present the case of CBO and CD
      but without any symptoms of this condition.

PMID- 16454223
TI  - Ectopic thymoma simulating a pericardial cyst.
AB  - We present a case of a 53 year old man with a thymoma near the pericardium, a
      rare ectopic localisation of thymoma. A round radiodensity found at the right
      cardiophrenic angle was initially suspected at the echocardiography to be a
      pericardial cyst. The diagnosis of thymoma was made only after histopathological
      examination of the surgically re-sected lesion.

PMID- 16454224
TI  - Underuse of spirometry in the diagnosis of COPD.

PMID- 16454225
TI  - [Editorial and homage to Pr. P. Fondu].

PMID- 16454226
TI  - [Hemophilia A in Belgium in the past 40 years].

PMID- 16454227
TI  - [New therapeutic perspectives in hemophilia].
AB  - This paper describes the evolution of hemophilia care during the past fourty
      years, evolution that markedly improved the prognosis of this disorder in the
      developed world. Remaining problems and prospects for the future are presented.

PMID- 16454228
TI  - [Current developments on sickle cell disease].
AB  - Sickle cell disease is a genetic autosomal recessive disease of hemoglobin. The
      disease results from a mutation of the sixth codon of the beta-globin gene, which
      induces the synthesis of an abnormal hemoglobin called hemoglobin S (HbS). The
      polymerisation of deoxy HbS molecules causes a chronic hemolytic anemia and vaso
      occlusive phenomenons. The disease affects mainly people from West Indies and Sub
      saharian Africa. Due to recent movements of these populations over the past
      years, sickle cell disease has spread across all continents. Painful crises,
      severe infections such as septicemia, meningitis, osteomyelytis, acute anemia
      episodes, and severe vaso-occlusive events, mainly neurological, are the most
      frequent complications affecting children. Recent progresses in the care of
      patients have deeply modified the prognosis. The mean life expectancy of patients
      is now above 40 years. The conventional treatment includes antibiotics and
      immunizations, analgesics, and blood transfusion. The effects of chronic blood
      transfusion, hydroxyurea and bone marrow transplantation are the subject of
      current comparative evaluations.

PMID- 16454229
TI  - [Hematopoietic stem cell transplantation for severe sickle cell disease].
AB  - Hematopoietic stem cell transplantation is the sole curative therapy for sickle
      cell anemia (SCA). This treatment is restricted to severe forms of disease. Lack
      of HLA-identical sibling donor is the major limiting factor for delivering this
      therapy. Conditioning regimen should be myeloablative. Post transplantation
      immunosuppressive medication is necessary for both graft tolerance and graft
      versus-host disease (GvHD) control. For the majority of patients, bone marrow is
      source of stem cells. Alternative sources including related cord blood stem cells
      are under evaluation and promising. Outcome for 250 grafted patients worldwide is
      excellent. More than 85 % survive free of SCA and have a good quality of life
      although GvHD remains the main complication.

PMID- 16454230
TI  - [Pediatric venous thromboembolism: review of the literature and news].
AB  - Pediatric venous thromboembolism is a multifactorial disorder with an annual
      incidence of 1/100.000 patients (0-18 years). The presence of central venous
      catheters is a major trigger for development of venous thrombosis, especially in
      neonates. As a consequence, thrombosis in the upper extremities are much more
      frequent in children than in adults. Congenital prothrombotic disorders may play
      a role in children thrombosis, often in combination with several acquired risk
      factors like immobilization, serious illness and/or hospitalization. Diagnosis is
      most frequently made by noninvasive radiologic techniques, like ultrasonography.
      Prophylaxis and treatment are extrapolated from adult patient protocols or small
      observational studies performed in small groups of patients.

PMID- 16454231
TI  - [Transfusion-related acute lung injury (TRALI): emerging or main transfusion
      hazard?].
AB  - Transfusion-Related Acute Lung Injury or TRALI is one of the most frequent severe
      transfusion reactions ( one third of Non Hemolytic Febrile Transfusion
      Reactions). It presents as a generally mild form of acute respiratory distress
      syndrome occurring 1 to 2 hours after transfusion of a plasma-containing blood
      component. This transfusion reaction appears, most of the time, in patients with
      focal inflammation and is of good prognosis when adequately diagnosed and
      treated. TRALI prevention rests on donor selection for plasma donation,
      hemovigilance system effectiveness and restrictive transfusion strategy.

PMID- 16454233
TI  - A tale of two States.

PMID- 16454234
TI  - Providing care for uninsured children.

PMID- 16454232
TI  - [The determinant role of an accurate medicosocial approach in the prognosis of
      pediatric blood diseases].
AB  - The care of infancy and childhood blood diseases implies a comprehensive
      medicosocial approach. This is a prerequisite for regular follow-up, for
      satisfactory compliance to treatment and for optimal patient's quality of life.
      Different modalities of medicosocial approach have been developed in the
      pediatric department (firstly in the Hospital Saint Pierre and than in the
      Children's University Hospital HUDERF). The drastic importance of a recent reform
      of the increased family allowances is briefly presented. The author underlines
      the determinant role of an accurate global approach, in which the patient and the
      family are surrounded by a multidisciplinary team, including social workers.

PMID- 16454235
TI  - Significant gains made in America's oral health.

PMID- 16454236
TI  - Dental student research: helping to shape the future.

PMID- 16454237
TI  - Dental caries and chemical warfare within the mouth.
AB  - To date, it appears that the dentists' war against dental caries has no end in
      sight due to the fact that dentists lack any genuine offensive firepower. Make no
      mistake, the defense has drastically improved as dentists have shifted the focus
      more toward the preventive aspects of dental care. But defense by itself cannot
      defeat the enemy; at best, it can maintain the status quo. In order to defeat the
      enemy, one must study and understand the enemy, to know its strengths and
      weaknesses, and to strike at those points of vulnerability. The aim of this
      research is to identify and characterize genes that are responsible for observed
      virulence factors in Streptococcus mutans, which is the primary pathogen involved
      in the development of dental caries. Once there is a more defined understanding
      of the many virulence factors of S. mutans, there will be a much more valuable
      insight into its role in the ecology of the oral cavity. Eventually, this
      knowledge could enable dentists to convert the bacterial "weaponry" into its own
      arsenal, which could then be innovatively employed as preventive, diagnostic, and
      therapeutic agents to treat oral bacterial-related diseases.

PMID- 16454238
TI  - Celebrex offers a small protection from root resorption associated with
      orthodontic movement.
AB  - Tooth movement results from alveolar bone resorption/deposition following
      application of orthodontic forces, and root resorption can be an undesirable
      complication associated with this process. No treatment for external root
      resorption is available to date. OBJECTIVE: To determine if COX-2 inhibitors like
      Celebrex are effective in protecting root resorption associated with orthodontic
      forces. METHODS: A force of 80 grams was applied to the left maxillary first
      molars of 7-week-old female Wistar rats using nickel titanium closed coil springs
      attached to the cervical area of the incisors with 0.010 stainless-steel ligature
      wires. Twenty animals were divided into three experimental groups: one receiving
      no treatment, the second receiving 25mg/kg, and the third receiving 50 mg/kg of
      celecoxib (Celebrex) in their drinking water. Rats were maintained on a soft diet
      and euthanized two weeks after initial placement of the force. Paraffin-embedded
      sections of the right (control) and left (experimental) maxillae were stained
      with H&E and the areas of root resorption were examined by counting the number of
      lacunaes in the roots. RESULTS: No difference in the distance of tooth movement
      (0.5 mm/two weeks) was seen in all three groups. The rats that received the low
      dose of Celebrex showed no statistically significant difference in root
      resorption than that of the rats that received no dose. The rats that received
      the high dose of Celebrex showed a lower number of lacunaes (mean = 3.5) than
      that of the control group (mean 10.2; p=0.02). CONCLUSIONS: Administration of
      Celebrex during the application of orthodontic forces does not interfere with
      tooth movement and appears to offer some slight protection against root
      resorption.

PMID- 16454239
TI  - The multifocal nature of odontogenic keratocysts.
AB  - The odontogenic keratocyst, OKC, is a very aggressive intraosseos lesion with a
      recurrence rate of approximately 25 percent to 60 percent.' The tendency for this
      lesion to "return" after surgical treatment has prompted studies to obtain more
      information concerning the inherent nature of the lesion. The OKC lesions are
      usually treated with enucleation of the soft tissue lining, curettage and
      ostectomy of the bony margins, or with more aggressive block resection. The
      purpose of this study was to characterize the multifocal aspect of the OKC and to
      demonstrate the presence of cystic lesions remote from the margins of the
      primarily diagnosed cyst itself. A retrospective chart review was conducted of
      seven patients who had sustained a long history of recurrent OKCs. Three types of
      documentation were reviewed for each patient: Orthopantomograms, cephalograms,
      and CT scans, which had been taken over the long-term course of the disease,
      Detailed operation reports of surgical procedures to treat the OKC lesions, and;
      Large histologic specimens from the six patients who received total resection of
      the involved mandibular bodies. These hemimandibulectomy slides offered a unique
      opportunity to observe OKC activity throughout a wide osseous area. All patients
      hod been operated multiple times over a period of 10 to 21 years, coming
      eventually to mandibular resection. The operating surgeon in all of the cases was
      one of the authors, Philip J. Boyne, DMD, MS, DSc. All patients exhibited the
      multifocal nature of OKCs with demonstrable cyst formation at distant sites in
      the mandible. Two patients had local recurrences at the margins of the primary
      lesion in addition to cyst formation at distant sites. The authors concluded that
      clinicians should respect the multifocal nature of OKCs. The "recurrences"
      observed in OKCs may not necessarily be due to the degree of skill of the surgeon
      or the technique used to eradicate the primary cyst, but instead are probably a
      reflection of the multifocal nature of the pathologic lesion itself. The OKC is a
      very aggressive intraosseos lesion of the jaws, which not infrequently clinicians
      detect in the process of routine oral examination.

PMID- 16454240
TI  - Gene therapy for oral cancer: efficient delivery of a 'suicide gene' to murine
      oral cancer cells in physiological milieu.
AB  - Gene therapy is a new therapeutic modality in which defective genes are replaced
      with functional ones, or genes are delivered that can specifically kill cancer
      cells. Efficient gene delivery is an important component of gene therapy
      approaches. Potential safety problems with viral vectors necessitate the
      development of efficient nonviral vectors. DNA complexes with synthetic cationic
      liposomes or polymers constitute a simple means of transferring DNA into target
      cells. Gene delivery mediated by many nonviral vectors, however, is inhibited by
      serum components, and this is expected to limit the efficiency of gene delivery
      in vivo. In this study, the authors examined two novel gene transfection
      reagents, Metafectene and GeneJammer, for their ability to deliver a reporter
      gene to SCCVII murine squamous cell carcinoma cells in the presence of high
      concentrations of mouse serum. After establishing conditions that achieved
      significant gene delivery, the authors introduced the Herpes Simplex Virus
      Thymidine kinase (HSV-tk) gene into the cells using the cationic liposome
      reagent, Metafectene, followed by the administration of ganciclovir. After seven
      days of incubation, 90 percent and 82 percent cytotoxicity was observed in 0
      percent and 60 percent mouse serum, respectively. The authors' observations
      suggest that Metafectene may be useful for the gene therapy of oral squamous cell
      carcinoma in a murine model involving the induction of oral tumors by SCCVII
      cells.

PMID- 16454242
TI  - The divine Ms. O.

PMID- 16454241
TI  - Cariogenic virulence characteristics of mutans streptococci isolated from caries
      active and caries-free adults.
AB  - The objective of the study was to compare aciduricity (ability, to live in acid),
      acidogenicity (ability to produce acid), and intracellular polysaccharide
      production of mutans streptococci (MS) strains isolated from caries-active (CA,
      with one or more cavitated lesions) and caries-free (CF, with no clinically
      observable new caries in the last five years) adults. Forty-three MS strains from
      17 of 17 CA adults, and 14 strains from eight of 12 CF adults were investigated.
      MS isolates' growth, survival, and pH reduction in pH 3.5-7.0 broths were
      evaluated to compare their acidogenicity and aciduricity. Extracellular water
      soluble polysaccharide (WSP) and water-insoluble polysaccharide (WISP) was
      extracted from MS culture in BHI broth with 5 percent sucrose and assessed by a
      colorimetric anthrone-sulfuric acid microassay. No significant differences in
      mean aciduricity were found between CA and CF MS isolates (P>0.05, t test).
      However, significantly more CA subjects (29 percent) were colonized by MS strains
      with aciduricity above the average than CF subjects (13 percent, Fisher's exact
      test, P<0.05). Furthermore, CA MS strains produced significantly more acid at
      pH<5 (Mann-Whitney, P<0.05) and significantly more CA subjects were colonized
      with more acidogenic MS at pH<4.5 (Fisher's exact test, P<0.01). Similarly, CA MS
      isolates produced significantly more WISP than CF (Mann-Whitney test, P<0.01)
      while no statistical difference was found in WSP between the two groups. More CA
      subjects were colonized by multiple strains with aciduricity, acidogenicity, and
      polysaccharide synthesis ability above average. The study indicated that
      differences in acidogenicity, aciduricity, and polysaccharide synthesis in
      strains of MS may partially contribute to increased caries activity.

PMID- 16454244
TI  - [What is new in the biology and prognosis of breast cancer?].

PMID- 16454243
TI  - [Older antipsychotic drugs have proven to be equally effective with the newer
      treatments].

PMID- 16454245
TI  - [Vocal cord dysfunction-poorly known factor of airway obstruction].

PMID- 16454246
TI  - [Nobel prize in medicine goes to the helicobacter researchers].

PMID- 16454247
TI  - [Work at the visual display unit].

PMID- 16454248
TI  - [Finnish type mutations leading to heart disorders].

PMID- 16454249
TI  - [Liver damage in methotrexate-treated patients. When liver biopsy is necessary in
      the follow-up?].

PMID- 16454250
TI  - [Consensus on obesity-heavy facts on weight].

PMID- 16454251
TI  - [Update on current care guidelines. Celiac disease].

PMID- 16454252
TI  - [Unusual fever of an ice skater].

PMID- 16454253
TI  - [Etiology of schizophrenia].

PMID- 16454254
TI  - [Polyneuropathy specifically diagnosed using EMG]].

PMID- 16454255
TI  - [About allogenic stem cell transplantation among children].

PMID- 16454256
TI  - [Response to previous letter to editor].

PMID- 16454257
TI  - [Is alcohol normalizing factor?].

PMID- 16454259
TI  - Alternate proof of the optical theorem for impenetrable targets.
AB  - The optical theorem is proven for impenetrable targets without using the method
      of stationary phase. The proof depends upon the divergence theorem, the Helmholtz
      representation of the scattered field, and the law of cosines.

PMID- 16454260
TI  - A study of the influence of mounting conditions on the measured sound absorption
      in laboratory tests of suspended ceilings.
AB  - This letter presents the results of an investigation into the influence of
      mounting conditions on the measured sound absorption coefficients of a suspended
      ceiling specimen. A series of measurements and analyses were carried out using a
      fixed standard sample, varying independently different mounting parameters and
      introducing controlled leaks. A correction of room volume in the calculation of
      the sound absorption coefficients was also examined. The tests were carried out
      in accordance with the ISO 354:2003 standard (International Organisation for
      Standardisation, Geneva, 2003), using the type E mounting. The test specimen
      consisted of fiberglass wool panels covered with a plastic film. Some of the
      experiments resulted in no statistically significant alteration. This included,
      unexpectedly, the sealing requirements of E type mountings.

PMID- 16454261
TI  - Discrimination of depth of sinusoidal amplitude modulation with and without roved
      carrier levels.
AB  - Thresholds for the discrimination of the depth of sinusoidal amplitude modulation
      with a broadband noise carrier were measured for three listeners in a two
      alternative, forced-choice task for modulation frequencies of 8, 32, and 128 Hz.
      Thresholds were measured with the spectrum level of the carrier fixed at 20 dB
      across all trials and, separately, with the carrier spectrum level roved randomly
      over a 20-dB range (10-30 dB) in each interval. Mean thresholds were equal or
      slightly lower (but not significantly so) for the fixed conditions relative to
      the roved conditions, and the differences between thresholds were too small to be
      explained by assuming that listeners compared instantaneous intensity at
      corresponding phases of the modulation cycle (for example, in the troughs).
      Rather, it appears that listeners discriminated modulation depth by extracting an
      estimate of the modulation depth within each interval that was independent of the
      overall level. Consequently, models of envelope extraction must include
      normalization of the envelope fluctuations to the envelope dc.

PMID- 16454262
TI  - Measuring the acoustic effects of compression amplification on speech in noise.
AB  - This letter contains a description of an inversion technique that allows for
      separation of speech and noise and its application to quantifying the acoustic
      effects of wide-dynamic-range compression (WDRC) on speech in background noise.
      Three main findings are reported: that fast-acting WDRC further degrades signal
      to-noise ratio; that the effective compression ratio is lower for speech in noise
      than speech in quiet; and that in contrast to speech in quiet, the amplitude
      envelope of speech is mostly unaffected when compressed in background noise.

PMID- 16454263
TI  - Hybrid compliance-stiffness matrix method for stable analysis of elastic wave
      propagation in multilayered anisotropic media.
AB  - This paper presents the hybrid compliance-stiffness matrix method for stable
      analysis of elastic wave propagation in multilayered anisotropic media. The
      method utilizes the hybrid matrix of each layer in a recursive algorithm to
      deduce the stack hybrid matrix for a multilayered structure. Like the stiffness
      matrix method, the hybrid matrix method is able to eliminate the numerical
      instability of transfer matrix method. By operating with total stresses and
      displacements, it also preserves the convenience for incorporating imperfect or
      perfect interfaces. However, unlike the stiffness matrix, the hybrid matrix
      remains to be well-conditioned and accurate even for zero or small thicknesses.
      The stability of hybrid matrix method has been demonstrated by the numerical
      results of reflection and transmission coefficients. These results have been
      determined efficiently based on the surface hybrid matrix method involving only a
      subset of hybrid submatrices. In conjunction with the recursive asymptotic
      method, the hybrid matrix method is self-sufficient without hybrid asymptotic
      method and may achieve low error level over a wide range of sublayer thickness or
      the number of recursive operations.

PMID- 16454264
TI  - A large ultrasonic bounded acoustic pulse transducer for acoustic transmission
      goniometry: modeling and calibration.
AB  - A large, flat ultrasonic transmitter and a small receiver are developed for
      studies of material properties in acoustic transmission goniometry. While the
      character of the wave field produced by the transmitter can be considered as a
      plane wave as observed by the receiver, diffraction effects are noticeable near
      critical angles and result in the appearance of weak but detectable arrivals.
      Transmitted ultrasonic waveforms are acquired in one elastic silicate glass and
      two visco-elastic acrylic glass sample plates as a function of the angle of
      incidence. Phase velocities are determined from modeling of the shape of curves
      of the observed arrival times versus angle of incidence. The waveform
      observations are modeled using a phase propagation technique that incorporates
      full wave behavior including attenuation. Subtle diffraction effects are captured
      in addition to the main bounded pulse propagation. The full propagation modeling
      allows for various arrivals to be unambiguously interpreted. The results of the
      plane wave solution are close to the full wave propagation modeling without any
      corrections to the observed wave field. This is an advantage as it places
      confidence that later analyses can use simpler plane wave solutions without the
      need for additional diffraction corrections. A further advantage is that the
      uniform bounded acoustic pulse allows for the detection of weak arrivals such as
      a low energy edge diffraction observed in our experiments.

PMID- 16454265
TI  - Inverse potential scattering in duct acoustics.
AB  - The inverse problem of the noninvasive measurement of the shape of an acoustical
      duct in which one-dimensional wave propagation can be assumed is examined within
      the theoretical framework of the governing Klein-Gordon equation. Previous
      deterministic methods developed over the last 40 years have all required direct
      measurement of the reflectance or input impedance but now, by application of the
      methods of inverse quantum scattering to the acoustical system, it is shown that
      the reflectance can be algorithmically derived from the radiated wave. The
      potential and area functions of the duct can subsequently be reconstructed. The
      results are discussed with particular reference to acoustic pulse reflectometry.

PMID- 16454266
TI  - An ultrasonic method for dynamic monitoring of fatigue crack initiation and
      growth.
AB  - Attached ultrasonic sensors can detect changes caused by crack initiation and
      growth if the wave path is directed through the area of critical crack formation.
      Dynamics of cracks opening and closing under load cause nonlinear modulation of
      received ultrasonic signals, enabling small cracks to be detected by stationary
      sensors. A methodology is presented based upon the behavior of ultrasonic signals
      versus applied load to detect and monitor formation and growth of cracks
      originating from fastener holes. Shear wave angle beam transducers operating in
      through transmission mode are mounted on either side of the hole such that the
      transmitted wave travels through the area of expected cracking. Time shift is
      linear with respect to load, and is well explained by path changes due to strain
      combined with wave speed changes due to acoustoelasticity. During subsequent in
      situ monitoring with unknown loads, the measured time of flight is used to
      estimate the load, and behavior of the received energy as a function of load is
      the basis for crack detection. Results are presented from low cycle fatigue tests
      of several aluminum specimens and illustrate the efficacy of the method in both
      determining the applied load and monitoring crack initiation and growth.

PMID- 16454267
TI  - The near-ground structure of the nocturnal sound field.
AB  - The near-ground behavior of the low-frequency (100 Hz to 500 Hz) sound field in
      the nocturnal sound duct is studied theoretically and experimentally. In the
      first few meters of the atmosphere, narrow-band sound fields are found to have a
      characteristic vertical structure. The sound field is the superposition of a
      "surface mode," whose magnitude decreases monotonically with altitude, with a sum
      of "higher modes," each of whose magnitudes has a pronounced minimum a few meters
      from the ground at approximately the same height. The surface mode attenuates to
      negligible levels after a few hundred meters from the source. Consequently, more
      than a few hundred meters from a narrow-band source, there is a "quiet height" at
      which the sound level is reduced by 10 to 15 dB relative to its value on the
      ground. The narrow-band quiet height is shown to be a robust feature of nocturnal
      sound propagation.

PMID- 16454268
TI  - Singular meshless method using double layer potentials for exterior acoustics.
AB  - Time-harmonic exterior acoustic problems are solved by using a singular meshless
      method in this paper. It is well known that the source points cannot be located
      on the real boundary, when the method of fundamental solutions (MFS) is used due
      to the singularity of the adopted kernel functions. Hence, if the source points
      are right on the boundary the diagonal terms of the influence matrices cannot be
      derived. Herein we present an approach to obtain the diagonal terms of the
      influence matrices of the MFS for the numerical treatment of exterior acoustics.
      By using the regularization technique to regularize the singularity and
      hypersingularity of the proposed kernel functions, the source points can be
      located on the real boundary and therefore the diagonal terms of influence
      matrices are determined. We also maintain the prominent features of the MFS, that
      it is free from mesh, singularity, and numerical integration. The normal
      derivative of the fundamental solution of the Helmholtz equation is composed of a
      two-point function, which is one of the radial basis functions. The solution of
      the problem is expressed in terms of a double-layer potential representation on
      the physical boundary based on the potential theory. The solutions of three
      selected examples are used to compare with the results of the exact solution,
      conventional MFS, boundary element method, and Dirichlet-to-Neumann finite
      element method. Good numerical performance is demonstrated by close agreement
      with other solutions.

PMID- 16454269
TI  - High frequency formulation for the acoustic power spectrum due to cascade
      turbulence interaction.
AB  - This paper investigates the noise radiated by a cascade of flat-plate airfoils
      interacting with homogeneous, isotropic turbulence. An analytic formulation for
      the spectrum of acoustic power of a two-dimensional flat-plate is derived. The
      main finding of this paper is that the acoustic power spectrum from the cascade
      of flat airfoils may be split into two distinct frequency regions of low
      frequency and high frequency, separated by a critical frequency. Below this
      frequency, cascade effects due to the interaction between neighboring airfoils
      are shown to be important. At frequencies above the critical frequency, cascade
      effects are shown to be relatively weak. In this frequency range, acoustic power
      is shown to be approximately proportional to the number of blades. Based on this
      finding at high frequencies, an approximate expression is derived for the power
      spectrum that is valid above the critical frequency and which is in excellent
      agreement with the exact expression for the broadband power spectrum. The
      formulation is used to perform a parametric study on the effects on the power
      spectrum of the blade number, stagger angle, gap-chord ratio, and Mach number.
      The theory is also shown to provide a close fit to the measured spectrum of rotor
      stator interaction.

PMID- 16454270
TI  - On the acoustic field in a Pekeris waveguide with attenuation in the bottom half
      space.
AB  - The acoustic field in a Pekeris channel with an attenuating basement is
      critically examined, based on contour integrations of the wave number integrals
      for the two domains. In both regions, the field consists of a finite sum of
      proper (square integrable) normal modes plus a branch line integral around a
      hyperbolic cut. For low bottom attenuation, only "trapped" modes exist but as the
      loss increases additional "dissipation" modes contribute to the mode sum. A
      Newton-Raphson iterative procedure is introduced for finding the complex
      eigenvalues of the modes and a new expression is derived which shows that the
      total number of proper (trapped plus dissipation) modes supported by the
      waveguide increases essentially linearly with rising bottom attenuation.
      Approximations for the complex shape functions of the modes in the water column
      and the basement are developed and compared with the exact shape functions
      determined from the Newton-Raphson procedure. An expression derived for the modal
      attenuation coefficient scales in proportion to the square of the mode number and
      inversely with the square of the frequency. Stationary-phase approximations for
      the branch line integrals for both domains are developed, which serve to
      illustrate the asymptotic range dependence of the lateral wave but otherwise have
      little utility.

PMID- 16454271
TI  - Broadband modeling of downslope propagation in a penetrable wedge.
AB  - Sound propagation in a wedge-shaped environment with a penetrable bottom is
      simulated with broadband adiabatic mode, coupled mode, and parabolic equation
      model computations. Simulated results are compared to measured data taken in a
      tank experiment by Tindle et al. The coupled mode formalism is shown to predict,
      in agreement with that experiment, that modal wave fronts in penetrable wedges
      are approximately circular arcs centered at the apex of the wedge for a source
      near the apex. It is also shown that for wedge angles up to 6 degrees, the
      received waveforms are well approximated by the adiabatic waveforms time-shifted
      by a depth-dependent interval to account for the curvature of the modal wave
      fronts. A small deviation from circularity in the modal wave fronts is possibly
      observed in the 6 degrees case.

PMID- 16454272
TI  - A reflected energy prediction model for long-range hydroacoustic reflection in
      the oceans.
AB  - Acoustic energy from underwater earthquakes and explosions can propagate over
      long distances with very little attenuation in the deep ocean. When this sound
      encounters a seamount, island, or continental margin, it can scatter and again
      propagate over long distances. Hydrophones in the deep sound channel can detect
      these reflections tens of minutes or hours after arrivals from the direct source
      to-receiver path. This paper presents the Reflected Energy Prediction (REP)
      model, a model for predicting these reflected arrivals. For a given source and
      receiver, the REP model uses a detailed knowledge of the underwater environment
      and components of the Hydroacoustic Coverage Assessment Model, HydroCAM, to
      predict the impulse response of the ocean. When this impulse response is
      convolved with a source function, a waveform envelope prediction is made that can
      be compared with recorded data. In this paper we present the model and a few
      applications of the model using data recorded from earthquakes and explosions in
      the Atlantic and Indian Oceans. These examples illustrate the use of the model
      and initial steps toward model calibration.

PMID- 16454273
TI  - Stepwise coupled mode scattering of ambient noise by a cylindrically symmetric
      seamount.
AB  - The question of how underwater ambient noise, at low frequencies, interacts with
      seamounts is addressed. The vertical directivity of the ambient noise, with and
      without the seamount interaction, is of particular interest. The problem of
      ambient noise scattering by seamounts motivates the development of a numerical
      modeling procedure, based on stepwise coupled modes. The procedure is designed to
      analyze scattering from a cylindrically symmetric seamount. The stepwise coupled
      mode procedure is extended to more general boundary conditions and brought up to
      date in the process. An example, using the geometry of the Dickins seamount,
      suggests that the seamount removes energy from the steeply traveling ambient
      noise, for this case. The energy is not converted into angles near the
      horizontal; the energy is lost through bottom interaction and attenuation.

PMID- 16454274
TI  - Ocean acoustic hurricane classification.
AB  - Theoretical and empirical evidence are combined to show that underwater acoustic
      sensing techniques may be valuable for measuring the wind speed and determining
      the destructive power of a hurricane. This is done by first developing a model
      for the acoustic intensity and mutual intensity in an ocean waveguide due to a
      hurricane and then determining the relationship between local wind speed and
      underwater acoustic intensity. From this it is shown that it should be feasible
      to accurately measure the local wind speed and classify the destructive power of
      a hurricane if its eye wall passes directly over a single underwater acoustic
      sensor. The potential advantages and disadvantages of the proposed acoustic
      method are weighed against those of currently employed techniques.

PMID- 16454275
TI  - Sounds from an oil production island in the Beaufort Sea in summer:
      characteristics and contribution of vessels.
AB  - The objective of this study was to determine the levels, characteristics, and
      range dependence of underwater and in-air sounds produced during the open-water
      seasons of 2000-2003 by the Northstar oil development, located in nearshore
      waters of the Alaskan Beaufort Sea. Specifically, sounds originating at the
      island itself (from construction, drilling, and oil production activities) were
      compared with sounds produced by vessels performing island support. Sounds were
      obtained with boat-based recordings (at distances up to 37 km from Northstar), a
      cabled hydrophone (distance approximately 450 m), and with autonomous seafloor
      recorders (distance approximately 22 km). Vessels (crew boat, tugs, self
      propelled barges) were the main contributors to the underwater sound field and
      were often detectable underwater as much as approximately 30 km offshore. Without
      vessels, broadband island sounds reached background values at 2-4 km. Island
      sound levels showed more variation (lower min, higher max) during construction
      than during drilling and production. In-air broadband measurements were not
      affected by the presence of vessels and reached background values 1-4 km from
      Northstar. However, one airborne tone (81 Hz) believed to originate at Northstar
      was still detectable in the spectrum 37 km away.

PMID- 16454276
TI  - Uncertainty analysis in matched-field geoacoustic inversions.
AB  - Quantifying uncertainty for parameter estimates obtained from matched-field
      geoacoustic inversions using a Bayesian approach requires estimation of the
      uncertainties in the data due to ambient noise as well as modeling errors. In
      this study, the variance parameter of the Gaussian error model, hereafter called
      error variance, is assumed to describe the data uncertainty. In practice, this
      parameter is not known a priori, and choosing a particular value is often
      difficult. Hence, to account for the uncertainty in error variance, several
      methods are introduced for implementing both the full and empirical Bayesian
      approaches. A full Bayesian approach that permits uncertainty of the error
      variance to propagate through the parameter estimation processes is a natural way
      of incorporating the uncertainty of error variance. Due to the large number of
      unknown parameters in the full Bayesian uncertainty analysis, an alternative, the
      empirical Bayesian approach, is developed, in which the posterior distributions
      of model parameters are conditioned on a point estimate of the error variance.
      Comparisons between the full and empirical Bayesian inferences of model
      parameters are presented using both synthetic and experimental data.

PMID- 16454277
TI  - Data error covariance in matched-field geoacoustic inversion.
AB  - Many approaches to geoacoustic inversion are based implicitly on the assumptions
      that data errors are Gaussian-distributed and spatially uncorrelated (i.e., have
      a diagonal covariance matrix). However, the latter assumption is often not valid
      due to theory errors, and can lead to reduced accuracy for geoacoustic parameter
      estimates and underestimation of parameter uncertainties. This paper examines the
      effects of data error (residual) covariance in matched-field geoacoustic
      inversion. An inversion approach is developed based on a nonparametric method of
      estimating the full covariance matrix (including off-diagonal terms) from the
      data residuals and explicitly including this covariance in the misfit function.
      Qualitative and quantitative statistical tests for Gaussianity and for
      correlations in complex residuals are considered to validate the inversion
      results. The approach is illustrated for Bayesian geoacoustic inversion of
      broadband, vertical-array acoustic data measured in the Mediterranean Sea.

PMID- 16454278
TI  - Validity of the Markov approximation in ocean acoustics.
AB  - Moment equations and path integrals for wave propagation in random media have
      been applied to many ocean acoustics problems. Both these techniques make use of
      the Markov approximation. The expansion parameter, which must be less than one
      for the Markov approximation to be valid, is the subject of this paper. There is
      a standard parameter (the Kubo number) which various authors have shown to be
      sufficient. Fourth moment equations have been successfully used to predict the
      experimentally measured frequency spectrum of intensity in the mid-ocean acoustic
      transmission experiment (MATE). Yet, in spite of this success, the Kubo number is
      greater than 1 for the measured index of refraction variability for MATE,
      arriving at a contradiction. Here, that contradiction is resolved by showing that
      the Kubo parameter is far too pessimistic for the ocean case. Using the
      methodology of van Kampen, another parameter is found which appears to be both
      necessary and sufficient, and is much smaller than the Kubo number when phase
      fluctuations are dominated by large scales in the medium. This parameter is shown
      to be small for the experimental regime of MATE, justifying the applications of
      the moment equations to that experiment.

PMID- 16454279
TI  - Improved parameterization of Antarctic krill target strength models.
AB  - There are historical discrepancies between empirical observations of Antarctic
      krill target strength and predictions using theoretical scattering models. These
      differences are addressed through improved understanding of key model parameters.
      The scattering process was modeled using the distorted-wave Born approximation,
      representing the shape of the animal as a bent and tapered cylinder. Recently
      published length-based regressions were used to constrain the sound speed and
      density contrasts between the animal and the surrounding seawater, rather than
      the earlier approach of using single values for all lengths. To constrain the
      parameter governing the orientation of the animal relative to the incident
      acoustic wave, direct measurements of the orientation of krill in situ were made
      with a video plankton recorder. In contrast to previous indirect and aquarium
      based observations, krill were observed to orient themselves mostly horizontally.
      Averaging predicted scattering over the measured distribution of orientations
      resulted in predictions of target strength consistent with in situ measurements
      of target strength of large krill (mean length 40-43 mm) at four frequencies (43
      420 kHz), but smaller than expected under the semi-empirical model traditionally
      used to estimate krill target strength.

PMID- 16454280
TI  - Acoustic waves generated by a laser point pulse in a transversely isotropic
      cylinder.
AB  - A three-dimensional (3D) model is presented to predict the acoustic waves
      generated by a laser point pulse in a transversely isotropic cylinder. The
      Fourier series expansion and the two-dimensional Fourier transform are introduced
      to calculate the 3D transient response under either the ablation or the
      thermoelastic generation. The presented physical model and the numerical inverse
      scheme are applied to a fiber reinforced composite cylinder with a strong
      anisotropy. Experimental radial displacements of the cylinder surface are
      detected by the laser ultrasonic technique and analyzed by the ray trajectories
      for both generation regimes. Corresponding theoretical displacements are obtained
      numerically and compared to the experimental signals. Good agreement is found
      between theoretical and experimental results. The focusing effects that
      anisotropy gives rise to are observed in both theory and experiment under either
      regime.

PMID- 16454281
TI  - Pressure-sensitive paint as a distributed optical microphone array.
AB  - Pressure-sensitive paint is presented and evaluated in this article as a
      quantitative technique for measurement of acoustic pressure fluctuations. This
      work is the culmination of advances in paint technology which enable unsteady
      measurements of fluctuations over 10 kHz at pressure levels as low as 125 dB.
      Pressure-sensitive paint may be thought of as a nano-scale array of optical
      microphones with a spatial resolution limited primarily by the resolution of the
      imaging device. Thus, pressure-sensitive paint is a powerful tool for making high
      amplitude sound pressure measurements. In this work, the paint was used to record
      ensemble-averaged, time-resolved, quantitative measurements of two-dimensional
      mode shapes in an acoustic resonance cavity. A wall-mounted speaker generated
      nonlinear, standing acoustic waves in a rigid enclosure measuring 216 mm wide,
      169 mm high, and 102 mm deep. The paint recorded the acoustic surface pressures
      of the (1,1,0) mode shape at approximately 1.3 kHz and a sound pressure level of
      145.4 dB. Results from the paint are compared with data from a Kulite pressure
      transducer, and with linear acoustic theory. The paint may be used as a
      diagnostic technique for ultrasonic tests where high spatial resolution is
      essential, or in nonlinear acoustic applications such as shock tubes.

PMID- 16454282
TI  - Decentralized harmonic active vibration control of a flexible plate using
      piezoelectric actuator-sensor pairs.
AB  - We have investigated decentralized active control of periodic panel vibration
      using multiple pairs combining PZT actuators and PVDF sensors distributed on the
      panel. By contrast with centralized MIMO controllers used to actively control the
      vibrations or the sound radiation of extended structures, decentralized control
      using independent local control loops only requires identification of the
      diagonal terms in the plant matrix. However, it is difficult to a priori predict
      the global stability of such decentralized control. In this study, the general
      situation of noncollocated actuator-sensor pairs was considered. Frequency domain
      gradient and Newton-Raphson adaptation of decentralized control were analyzed,
      both in terms of performance and stability conditions. The stability conditions
      are especially derived in terms of the adaptation coefficient and a control
      effort weighting coefficient. Simulations and experimental results are presented
      in the case of a simply supported panel with four PZT-PVDF pairs distributed on
      it. Decentralized vibration control is shown to be highly dependent on the
      frequency, but can be as effective as a fully centralized control even when the
      plant matrix is not diagonal-dominant or is not strictly positive real (not
      dissipative).

PMID- 16454283
TI  - Effects of porous covering on sound attenuation by periodic arrays of cylinders.
AB  - The acoustic transmission loss of a finite periodic array of long rigid
      cylinders, without and with porous absorbent covering, is studied both
      theoretically and in the laboratory. A multiple scattering model is extended to
      allow for the covering and its acoustical properties are described by a single
      parameter semi-empirical model. Data from laboratory measurements and numerical
      results are found to be in reasonable agreement. These data and predictions show
      that porous covering reduces the variation of transmission loss with frequency
      due to the stop/pass band structure observed with an array of rigid cylinders
      with similar overall radius and improves the overall attenuation in the higher
      frequency range. The predicted sensitivities to covering thickness and effective
      flow resistivity are explored. It is predicted that a random covered array also
      gives better attenuation than a random array of rigid cylinders with the same
      overall radius and volume fraction.

PMID- 16454284
TI  - Wave reflection and transmission reduction using a piezoelectric semipassive
      nonlinear technique.
AB  - This study addresses the problem of noise reduction using piezoelements. The
      nonlinear technique, synchronized switch damping (SSD), is implemented. The
      device is a pulse-tube termination equipped with piezoelements, which allows
      performant damping of the vibration resulting from an incident acoustic wave. Due
      to this damping, both reflected and transmitted wave are reduced. In the
      semipassive damping approach proposed in this paper, energy degradation is
      strongly enhanced when the piezoelements are continuously switched from open to
      short circuit synchronously to the strain. This technique has been developed
      following two strategies. The first is SSD on a short circuit in which the
      piezoelement is always in open circuit, except for a very brief period at each
      strain extremum where it is short-circuited. The second approach is SSD on an
      inductor. The process is very similar, except that instead of forcing the voltage
      to zero, the voltage is exactly reversed using a controlled oscillating discharge
      of the piezoelement capacitor on an inductor during switch drive. Due to this
      switching mechanism, a phase shift appears between the strain and the resulting
      voltage, thus creating energy dissipation. Following SSD on an piezoelement,
      attenuations of 15 dB in reflection and 7 dB in transmission were obtained.

PMID- 16454285
TI  - Subjective assessment of listening environments in university classrooms:
      perceptions of students.
AB  - A questionnaire is developed to evaluate perception of the listening environment
      by university students. The objectives were to develop a questionnaire-based
      measurement tool, derive a measure of perceived classroom-listening quality, use
      the questionnaire to investigate factors that enhance, impair, or do not affect
      perceived listening quality, and consider the implications for classroom design.
      The questionnaire was administered to over 5700 students in 30 classrooms at one
      university. Physical and acoustical measurements were also performed in each
      classroom. The questionnaire included items that recorded aspects of student
      perception, as well as individual, course-, and instructor-specific factors.
      Responses to 19 perception items generated a perception of listening ease (PLE)
      score for each student and a classroom-average score. Decreased PLE was
      associated with women, English-second-larguage students, those with hearing
      impairment, students not interested in the course material, and those who found
      the material difficult. Increased PLE was associated with higher speech
      transmission index, acceptable lighting, temperature and seating, better
      instructor voice, increased visual-aid use, and easier course material. Results
      indicate that PLE is a useful measure of student perception of the classroom
      listening environment, and that optimal classroom acoustical design must take
      into consideration "in-use" conditions, as well as classroom physical
      characteristics.

PMID- 16454286
TI  - Ternary and quadriphase sequence diffusers.
AB  - A room acoustic diffuser breaks up reflected wavefronts, and this can be achieved
      by presenting a spatially varying surface impedance. In hybrid surfaces, varying
      impedance is achieved by patches of absorption and reflection, giving reflection
      coefficients nominally of 0 and 1. These surfaces are hybrids, absorbing some of
      the incident sound while diffusing any reflected energy. A problem with planar
      hybrid surfaces is that specular energy is only removed by absorption. By
      exploiting interference, by reflecting waves out-of-phase with the specular
      energy, it is possible to diminish the specular energy further. This can be
      achieved by using a diffuser based on a ternary sequence that nominally has
      reflection coefficients of 0, -1, and +1. Ternary sequences are therefore a way
      of forming hybrid absorber-diffusers that achieve better scattering performance
      without additional absorption. This paper discusses methods for making ternary
      sequence diffusers, including giving sequence generation methods. It presents
      prediction results based on Fourier and boundary element method models to examine
      the performance. While ternary diffusers have better performance than unipolar
      binary diffusers at most frequencies, there are frequencies at which the
      performances are the same. This can be overcome by forming diffusers from four
      level, quadriphase sequences.

PMID- 16454287
TI  - Calibration of the pressure sensitivity of microphones by a free-field method at
      frequencies up to 80 khz.
AB  - A free-field (FF) substitution method for calibrating the pressure sensitivity of
      microphones at frequencies up to 80 kHz is demonstrated with both grazing and
      normal-incidence geometries. The substitution-based method, as opposed to a
      simultaneous method, avoids problems associated with the nonuniformity of the
      sound field and, as applied here, uses a 1/4-in. air-condenser pressure
      microphone as a known reference. Best results were obtained with a centrifugal
      fan, which is used as a random, broadband sound source. A broadband source
      minimizes reflection-related interferences that can plague FF measurements.
      Calibrations were performed on 1/4-in. FF air-condenser, electret, and
      microelectromechanical systems (MEMS) microphones in an anechoic chamber. The
      uncertainty of this FF method is estimated by comparing the pressure sensitivity
      of an air-condenser FF microphone, as derived from the FF measurement, with that
      of an electrostatic actuator calibration. The root-mean-square difference is
      found to be +/- 0.3 dB over the range 1-80 kHz, and the combined standard
      uncertainty of the FF method, including other significant contributions, is +/-
      0.41 dB.

PMID- 16454288
TI  - A specialized fast cross-correlation for acoustical measurements using coded
      sequences.
AB  - In acoustics applications, binary maximal-length sequences and related sequences
      are increasingly used for acoustics system identification tasks. A number of
      coded sequences, such as binary maximal-length related sequences and ternary
      sequences possess two-valued or pulselike autocorrelation functions. It is this
      correlation property that is exploited in most of acoustical applications.
      However, the length of some of these sequences is not directly suitable for FFT
      based cross-correlation algorithms. This paper explores using standard FFTs to
      calculate the cross-correlation between two periodic finite-length sequences of
      equal length, where the lengths of the sequences are not a power of 2. We apply
      our specialized correlation algorithm to analyze data collected in a room
      acoustic environment to simultaneously obtain impulse responses between multiple
      sources and multiple receivers.

PMID- 16454289
TI  - The array invariant.
AB  - A method is derived for instantaneous source-range estimation in a horizontally
      stratified ocean waveguide from passive beam-time intensity data obtained after
      conventional plane-wave beamforming of acoustic array measurements. The method
      has advantages over existing source localization methods, such as matched field
      processing or the waveguide invariant. First, no knowledge of the environment is
      required except that the received field should not be dominated by purely
      waterborne propagation. Second, range can be estimated in real time with little
      computational effort beyond plane-wave beamforming. Third, array gain is fully
      exploited. The method is applied to data from the Main Acoustic Clutter
      Experiment of 2003 for source ranges between 1 to 8 km, where it is shown that
      simple, accurate, and computationally efficient source range estimates can be
      made.

PMID- 16454290
TI  - A miniaturized adaptive microphone array under directional constraint utilizing
      aggregated microphones.
AB  - This paper introduces a miniaturized microphone array using the Directionally
      Constrained Minimization of Power (DCMP) method, which utilizes the transfer
      functions of microphones located at the same place, namely aggregated
      microphones. The phased microphone array realizes a noise reduction and direction
      of arrival (DOA) estimation system according to differences in the arrival time,
      phase shift, and/or the level of the sound wave for each microphone. Hence it is
      difficult to miniaturize the microphone array. The objective of our research is
      to miniaturize the system size using aggregated microphones. In this paper, we
      first show that the phased microphone array system and the proposed aggregated
      microphone system can be described within the same framework. We then apply a
      microphone array under directional constraint to the aggregated microphones and
      compare the proposed method with the microphone array. We show the directional
      pattern of the aggregated microphones. We also show the experimental results
      regarding DOA estimation.

PMID- 16454291
TI  - Algorithms for computing the time-corrected instantaneous frequency (reassigned)
      spectrogram, with applications.
AB  - A modification of the spectrogram (log magnitude of the short-time Fourier
      transform) to more accurately show the instantaneous frequencies of signal
      components was first proposed in 1976 [Kodera et al., Phys. Earth Planet. Inter.
      12, 142-150 (1976)], and has been considered or reinvented a few times since but
      never widely adopted. This paper presents a unified theoretical picture of this
      time-frequency analysis method, the time-corrected instantaneous frequency
      spectrogram, together with detailed implementable algorithms comparing three
      published techniques for its computation. The new representation is evaluated
      against the conventional spectrogram for its superior ability to track signal
      components. The lack of a uniform framework for either mathematics or
      implementation details which has characterized the disparate literature on the
      schemes has been remedied here. Fruitful application of the method is shown in
      the realms of speech phonation analysis, whale song pitch tracking, and additive
      sound modeling.

PMID- 16454292
TI  - Transducer sensitivity compensation using diagonal preconditioning for time
      reversal and Tikhonov inverse filtering in acoustic systems.
AB  - Filters are commonly used in sound reproduction and communication systems as a
      means of compensating for the response of the electro-acoustic plant. Two
      commonly used filter designs in the field of acoustics are the time reversal
      filter and the Tikhonov inverse filter. In this paper the influence of transducer
      sensitivities on the performance of these filters is examined. It is shown that
      the sensitivity of the transducers can negatively affect the performance of the
      resulting filter. To compensate for the decrease in performance, diagonal
      preconditioning can be implemented in the system. It is shown that by using
      diagonal matrices, which minimize the condition number of the system, the loss in
      performance arising from unbalanced sensitivities is minimized. This paper
      proposes an algorithm to find such a set of diagonal matrices and results are
      presented showing the improvements in performance arising from the modified
      filter design.

PMID- 16454293
TI  - Scan-based near-field acoustical holography and partial field decomposition in
      the presence of noise and source level variation.
AB  - Practical holography measurements of composite sources are usually performed
      using a multireference cross-spectral approach, and the measured sound field must
      be decomposed into spatially coherent partial fields before holographic
      projection. The formulations by which the latter approach have been implemented
      have not taken explicit account of the effect of additive noise on the reference
      signals and so have strictly been limited to the case in which noise superimposed
      on the reference signals is negligible. Further, when the sound field is measured
      by scanning a subarray over a number of patches in sequence, the decomposed
      partial fields can suffer from corruption in the form of a spatially distributed
      error resulting from source level variation from scan-to-scan. In the present
      work, the effects of both noise included in the reference signals, and source
      level variation during a scan-based measurement, on partial field decomposition
      are described, and an integrated procedure for simultaneously suppressing the two
      effects is provided. Also, the relative performance of two partial field
      decomposition formulations is compared, and a strategy for obtaining the best
      results is described. The proposed procedure has been verified by using numerical
      simulations and has been applied to holographic measurements of a subsonic jet.

PMID- 16454294
TI  - A hydromechanical biomimetic cochlea: experiments and models.
AB  - The construction, measurement, and modeling of an artificial cochlea (ACochlea)
      are presented in this paper. An artificial basilar membrane (ABM) was made by
      depositing discrete Cu beams on a piezomembrane substrate. Rather than two fluid
      channels, as in the mammalian cochlea, a single fluid channel was implemented on
      one side of the ABM, facilitating the use of a laser to detect the ABM vibration
      on the other side. Measurements were performed on both the ABM and the ACochlea.
      The measurement results on the ABM show that the longitudinal coupling on the ABM
      is very strong. Reduced longitudinal coupling was achieved by cutting the
      membrane between adjacent beams using a laser. The measured results from the
      ACochlea with a laser-cut ABM demonstrate cochlear-like features, including
      traveling waves, sharp high-frequency rolloffs, and place-specific frequency
      selectivity. Companion computational models of the mechanical devices were
      formulated and implemented using a circuit simulator. Experimental data were
      compared with simulation results. The simulation results from the computational
      models of the ABM and the ACochlea are similar to their experimental
      counterparts.

PMID- 16454295
TI  - Auditory-nerve first-spike latency and auditory absolute threshold: a computer
      model.
AB  - A computer model of the auditory periphery was used to address the question of
      what constitutes the physiological substrate of absolute auditory threshold. The
      model was first evaluated to show that it is consistent with experimental
      findings that auditory-nerve fiber spikes can be predicted to occur when the
      running integral of stimulus pressure reaches some critical value [P. Heil and H.
      Neubauer, J. Neurosci. 15, 7404-7415 (2001)]. It was then modified to examine two
      ways in which the accumulation and clearance of receptor presynaptic calcium
      might explain this effect. Both methods gave results that matched the animal
      data. It was also shown how the rate of clearance of presynaptic calcium could be
      used to explain the origin of differences between low and high spontaneous-rate
      fiber types. When spiking activity is aggregated across a number of similar high
      spontaneous-rate fibers and used as the input to a model of a cochlear nucleus
      coincidence neuron, its response can be used to judge whether or not a stimulus
      is present. A simulated psychophysical experiment then demonstrated that this
      simple decision procedure can reproduce measurements of absolute auditory
      threshold for tones in quiet where the threshold is a joint function of both time
      and level.

PMID- 16454296
TI  - Influence of primary-level and primary-frequency ratios on human distortion
      product otoacoustic emissions.
AB  - The combined influence of primary-level differences (L1-L2) and primary-frequency
      ratio (f2/f1) on distortion product otoacoustic emission (DPOAE) level was
      investigated in 20 normal-hearing subjects. DPOAEs were recorded with
      continuously varying stimulus levels [Neely et al. J. Acoust. Soc. Am. 117, 1248
      1259 (2005)] for the following stimulus conditions: f2= 1, 2, 4, and 8 kHz and
      f2/f1=1.05 to 1.4; various L1-L2, including one individually optimized to produce
      the largest DPOAE. For broadly spaced primary frequencies at low L2 levels, the
      largest DPOAEs were recorded when L1 was much higher than L2, with L1 remaining
      relatively constant as L2 increased. As f2/fl decreased, the largest DPOAEs were
      observed when L1 was closer to L2 and increased as L2 increased. Optimal values
      for L1-L2 and f2 f1 were derived from these data. In general, average DPOAE
      levels for the new L1-L2 and f2/f1 were equivalent to or larger than those
      observed for other stimulus combinations, including the L1-L2 described by Kummer
      et al. [J. Acoust. Soc. Am. 103, 3431-3444 (1998)] and those defined by Neely et
      al. in which L1-L2 was evaluated, but f2/f1 was fixed at 1.2.

PMID- 16454297
TI  - Signal-to-noise ratio and frequency analysis of continuous loop averaging
      deconvolution (CLAD) of overlapping evoked potentials.
AB  - In this study, a frequency domain formulation of continuous loop averaging
      deconvolution (CLAD) of overlapping evoked potentials is developed and applied
      for the extraction of transient responses from recordings obtained at high
      stimulation rates. This formulation allows for a faster execution of CLAD by
      using fast Fourier transform algorithms. The frequency characteristics of the
      deconvolution filter depends exclusively on the stimulus sequence and determines
      whether the noncoherent noise is amplified or attenuated in different
      frequencies. A formula for calculating the signal-to-noise ratio (SNR) achieved
      by the deconvolution process is developed. The newly developed theory and the
      methodology is applied to the extraction of the auditory brainstem and middle
      latency responses using various sequences. The effects of the sequence used and
      the number of sweeps averaged in ongoing acquisition on SNR are examined by using
      single sweep recordings. The results verify the deconvolution theory and the
      methodology and show its limitations. Depending on the frequency characteristics
      of the sequence, the deconvolution process can amplify or attenuate the EEG
      noise. Proper selection of the stimulus sequence can increase the SNR enhancement
      obtained with conventional averaging.

PMID- 16454298
TI  - Audition in sciaenid fishes with different swim bladder-inner ear configurations.
AB  - We investigated how morphological differences in the auditory periphery of
      teleost fishes may relate to hearing capabilities. Two species of western
      Atlantic sciaenids were examined: weakfish (Cynoscion regalis, Block and
      Schneider) and spot (Leiostomus xanthurus, Lacepede). These species differ in the
      anatomical relationship between the swim bladder and the inner ear. In weakfish,
      the swim bladder has a pair of anterior horns that terminate close to the ear,
      while there are no extensions of the swim bladder in spot. Thus, the swim bladder
      in spot terminates at a greater distance from the ear when compared to weakfish.
      With the use of the auditory brainstem response technique, Cynoscion regalis were
      found to detect frequencies up to 2000 Hz, while Leiostomus xanthurus detected up
      to 700 Hz. There were, however, no significant interspecific differences in
      auditory sensitivity for stimuli between 200 and 700 Hz. These data support the
      hypothesis that the swim bladder can potentially expand the frequency range of
      detection.

PMID- 16454300
TI  - Auditory filter nonlinearity across frequency using simultaneous notched-noise
      masking.
AB  - Psychoacoustic masking experiments have been widely used to investigate cochlear
      function in human listeners. Here we use simultaneous notched-noise masking
      experiments in normal hearing listeners to characterize the changes in auditory
      filter shape with stimulus level over the frequency range 0.25-6 kHz. At each
      frequency a range of fixed signal levels (30-70 dB SPL) and fixed masker levels
      (20-50 dB SPL spectrum level) are used in order to obtain accurate descriptions
      of the filter shapes in individual listeners. The notched-noise data for
      individual listeners are fitted with two filter shape models: a rounded
      exponential (roex) shape in which the filter skirt changes as a linear function
      of probe-tone level and the other, in which the gain of the tip filter relative
      to the filter tail changes as a function of signal level [Glasberg and Moore, J.
      Acoust. Soc. Am. 108, 2318-2328 (2000)]. The parameters for these fitted models
      are then described with a simple set of equations that quantify the changes in
      auditory filter shape across level and frequency. Both these models fitted the
      data equally well and both demonstrated increasing tip-tail gain as frequency
      increased.

PMID- 16454299
TI  - Level dependence of auditory filters in nonsimultaneous masking as a function of
      frequency.
AB  - Auditory filter bandwidths were measured using nonsimultaneous masking, as a
      function of signal level between 10 and 35 dB SL for signal frequencies of 1, 2,
      4, and 6 kHz. The brief sinusoidal signal was presented in a temporal gap within
      a spectrally notched noise. Two groups of normal-hearing subjects were tested,
      one using a fixed masker level and adaptively varying signal level, the other
      using a fixed signal level and adaptively varying masker level. In both cases,
      auditory filters were derived by assuming a constant filter shape for a given
      signal level. The filter parameters derived from the two paradigms were not
      significantly different. At 1 kHz, the equivalent rectangular bandwidth (ERB)
      decreased as the signal level increased from 10 to 20 dB SL, after which it
      remained roughly constant. In contrast, at 6 kHz, the ERB increased consistently
      with signal levels from 10 to 35 dB SL. The results at 2 and 4 kHz were
      intermediate, showing no consistent change in ERB with signal level. Overall, the
      results suggest changes in the level dependence of the auditory filters at
      frequencies above 1 kHz that are not currently incorporated in models of human
      auditory filter tuning.

PMID- 16454301
TI  - Sound source localization in real sound fields based on empirical statistics of
      interaural parameters.
AB  - The role of temporal fluctuations and systematic variations of interaural
      parameters in localization of sound sources in spatially distributed,
      nonstationary noise conditions was investigated. For this, Bayesian estimation
      was applied to interaural parameters calculated with physiologically plausible
      time and frequency resolution. Probability density functions (PDFs) of the
      interaural level differences (ILDs) and phase differences (IPDs) were estimated
      by measuring histograms for a directional sound source perturbed by several types
      of interfering noise at signal-to-noise ratios (SNRs) between -5 and +30 dB. A
      moment analysis of the PDFs reveals that the expected values shift and the
      standard deviations increase considerably with decreasing SNR, and that the PDFs
      have non-Gaussian shape at medium SNRs. A d' analysis of the PDFs indicates that
      elevation discrimination is possible even at low SNRs in the median plane by
      integrating information across frequency. Absolute sound localization was
      simulated by a Bayesian maximum a posteriori (MAP) procedure. The simulation is
      based on frequency integration of broadly tuned "detectors." Confusion patterns
      of real and estimated sound source directions are similar to those of human
      listeners. The results indicate that robust processing strategies are needed to
      exploit interaural parameters successfully in noise conditions due to their
      strong temporal fluctuations.

PMID- 16454302
TI  - Frequency discrimination of complex tones; assessing the role of component
      resolvability and temporal fine structure.
AB  - Thresholds for discriminating the fundamental frequency (FO) of a complex tone,
      FODLs, are small when low harmonics are present, but increase when the number of
      the lowest harmonic, N, is above eight. To assess whether the relatively small
      FODLs for N in the range 8-10 are based on (partly) resolved harmonics or on
      temporal fine structure information, FODLs were measured as a function of N for
      tones with three successive harmonics which were added either in cosine or
      alternating phase. The center frequency was 2000 Hz, and N was varied by changing
      the mean FO. A background noise was used to mask combination tones. The value of
      FO was roved across trials to force subjects to make within-trial comparisons. N
      was roved by +/- 1 for every stimulus, to prevent subjects from using excitation
      pattern cues. FODLs were not influenced by component phase for N= 6 or 7, but
      were smaller for cosine than for alternating phase once N exceeded 7, suggesting
      that temporal fine structure plays a role in this range. When the center
      frequency was increased to 5000 Hz, performance was much worse for low N,
      suggesting that phase locking is important for obtaining low FODLs with resolved
      harmonics.

PMID- 16454303
TI  - Factors affecting the use of noise-band vocoders as acoustic models for pitch
      perception in cochlear implants.
AB  - Although in a number of experiments noise-band vocoders have been shown to
      provide acoustic models for speech perception in cochlear implants (CI), the
      present study assesses in four experiments whether and under what limitations
      noise-band vocoders can be used as an acoustic model for pitch perception in CI.
      The first two experiments examine the effect of spectral smearing on simulated
      electrode discrimination and fundamental frequency (FO) discrimination. The third
      experiment assesses the effect of spectral mismatch in an FO-discrimination task
      with two different vocoders. The fourth experiment investigates the effect of
      amplitude compression on modulation rate discrimination. For each experiment, the
      results obtained from normal-hearing subjects presented with vocoded stimuli are
      compared to results obtained directly from CI recipients. The results show that
      place pitch sensitivity drops with increased spectral smearing and that place
      pitch cues for multi-channel stimuli can adequately be mimicked when the
      discriminability of adjacent channels is adjusted by varying the spectral slopes
      to match that of CI subjects. The results also indicate that temporal pitch
      sensitivity is limited for noise-band carriers with low center frequencies and
      that the absence of a compression function in the vocoder might alter the
      saliency of the temporal pitch cues.

PMID- 16454304
TI  - Perception of amplitude modulation by hearing-impaired listeners: the audibility
      of component modulation and detection of phase change in three-component
      modulators.
AB  - Two experiments were conducted to assess whether hearing-impaired listeners have
      a reduced ability to process suprathreshold complex patterns of modulation
      applied to a 4-kHz sinusoidal carrier. Experiment 1 examined the ability to "hear
      out" the modulation frequency of the central component of a three-component
      modulator, using the method described by Sek and Moore [J. Acoust. Soc. Am. 113,
      2801-2811 (2003)]. Scores were around 70-80% correct when the components in the
      three-component modulator were widely spaced and when the frequencies of the
      target and comparison different sufficiently, but decreased when the components
      in the modulator were closely spaced. Experiment 2 examined the ability to hear a
      change in the relative phase of the components in a three-component modulator
      with harmonically spaced components. The frequency of the central component, f,
      was either 50 or 100 Hz. Scores were about 70% correct when the component spacing
      was < or = 0.5fc, but decreased markedly for greater spacings. Performance was
      only slightly impaired by randomizing the overall modulation depth from one
      stimulus to the next. For both experiments, performance was only slightly worse
      than for normally hearing listeners, indicating that cochlear hearing loss does
      not markedly affect the ability to process suprathreshold complex patterns of
      modulation.

PMID- 16454305
TI  - Horizontal localization with bilateral hearing aids: without is better than with.
AB  - This paper studies the effect of bilateral hearing aids on directional hearing in
      the frontal horizontal plane. Localization tests evaluated bilateral hearing aid
      users using different stimuli and different noise scenarios. Normal hearing
      subjects were used as a reference. The main research questions raised in this
      paper are: (i) How do bilateral hearing aid users perform on a localization task,
      relative to normal hearing subjects? (ii) Do bilateral hearing aids preserve
      localization cues, and (iii) Is there an influence of state of the art noise
      reduction algorithms, more in particular an adaptive directional microphone
      configuration, on localization performance? The hearing aid users were tested
      without and with their hearing aids, using both a standard omnidirectional
      microphone configuration and an adaptive directional microphone configuration.
      The following main conclusions are drawn. (i) Bilateral hearing aid users perform
      worse than normal hearing subjects in a localization task, although more than one
      half of the subjects reach normal hearing performance when tested unaided. For
      both groups, localization performance drops significantly when acoustical
      scenarios become more complex. (ii) Bilateral, i.e., independently operating
      hearing aids do not preserve localization cues. (iii) Overall, adaptive
      directional noise reduction can have an additional and significant negative
      impact on localization performance.

PMID- 16454306
TI  - Distortion product otoacoustic emission (DPOAE) in tinnitus patients.
AB  - The aim of this study was to determine the effect of tinnitus (experiment I) and
      the combined effect of tinnitus and sensorineural hearing loss (experiment II) on
      the distortion product otoacoustic emission (DPOAE) for two age groups of
      tinnitus patients. Tinnitus patients with normal earing, along with normal
      hearing control subjects, participated in experiment I. They were divided into
      two age groups, below 50 and above 50 years. Experiment I showed that the DPOAE
      levels in the tinnitus patients were lower than those in the normal-hearing
      (nontinnitus) subjects. The differences depended on the frequency and the age of
      the patients, suggesting the confounding influence of presbyacusis. The second
      group of tinnitus patients with increasing and notch-like hearing loss
      participated in experiment II. They were also divided into two age groups, below
      50 and above 50 years. The data from experiment II showed that DPOAE activity
      well reflects the increasing and notch-like hearing loss functions up to about 40
      dB HL. The effect of age on the DPOAE level was clearly noted only for the
      tinnitus patients with clinically normal-hearing thresholds and was ambiguous for
      the tinnitus patients with hearing loss.

PMID- 16454307
TI  - The effect of glottal angle on intraglottal pressure.
AB  - Intraglottal pressure distributions depend upon glottal shape, size, and
      diameter. This study reports the effects of varying glottal angle on intraglottal
      and transglottal pressures using a three-dimensional Plexiglas model with a
      glottis having nine symmetric glottal angles and a constant minimal glottal
      diameter of 0.06 cm. The empirical data were supported by computational results
      using FLUENT. The results suggested that (1) the greater the convergent glottal
      angle, the greater outward driving forces (higher intraglottal pressures) on the
      vocal folds; (2) flow resistance was greatest for the uniform glottis, and least
      for the 10 degrees divergent glottis; (3) the greatest negative pressure in the
      glottis and therefore the greatest pressure recovery for diverging glottal shapes
      occurred for an angle of 10 degrees; (4) the smaller the convergent angle, the
      greater the flow resistance; (5) FLUENT was highly accurate in predicting the
      empirical pressures of this model; (6) flow separation locations (given by
      FLUENT) for the divergent glottis moved upstream for larger flows and larger
      glottal angles. The results suggest that phonatory efficiency related to
      aerodynamics may be enhanced with vocal fold oscillations that include large
      convergent angles during glottal opening and small (5 degrees - 10 degrees)
      divergent angles during glottal closing.

PMID- 16454308
TI  - Testing the assumptions of linear prediction analysis in normal vowels.
AB  - In this paper we develop an improved surrogate data test to show experimental
      evidence, for all the simple vowels of U.S. English, for both male and female
      speakers, that Gaussian linear prediction analysis, a ubiquitous technique in
      current speech technologies, cannot be used to extract all the dynamical
      structure of real speech time series. The test provides robust evidence
      undermining the validity of these linear techniques, supporting the assumptions
      of either dynamical nonlinearity and/or non-Gaussianity common to more recent,
      complex, efforts at dynamical modeling speech time series. However, an additional
      finding is that the classical assumptions cannot be ruled out entirely, and
      plausible evidence is given to explain the success of the linear Gaussian theory
      as a weak approximation to the true, nonlinear/non-Gaussian dynamics. This
      supports the use of appropriate hybrid linear/nonlinear/non-Gaussian modeling.
      With a calibrated calculation of statistic and particular choice of experimental
      protocol, some of the known systematic problems of the method of surrogate data
      testing are circumvented to obtain results to support the conclusions to a high
      level of significance.

PMID- 16454309
TI  - Speech perception from monaural and binaural information.
AB  - Two experiments explored the concept of the binaural spectrogram [Culling and
      Colburn, J. Acoust. Soc. Am. 107, 517-527 (2000)] and its relationship to
      monaurally derived information. In each experiment, speech was added to noise at
      an adverse signal-to-noise ratio in the NoS pi binaural configuration. The
      resulting monaural and binaural cues were analyzed within an array of spectro
      temporal bins and then these cues were resynthesized by modulating the intensity
      and/or interaural correlation of freshly generated noise. Experiment 1 measured
      the intelligibility of the resynthesized stimuli and compared them with the
      original NoSo and NoS pi stimuli at a fixed signal-to-noise ratio. While NoS pi
      stimuli were approximately equal to 50% intelligible, each cue in isolation
      produced similar (very low) intelligibility to the NoSo condition. The
      resynthesized combination produced approximately equal to 25% intelligibility.
      Modulation of interaural correlation below 1.2 kHz and of amplitude above 1.2 kHz
      was not as effective as their combination across all frequencies. Experiment 2
      measured three-point psychometric functions in which the signal-to-noise ratio of
      the original NoS pi stimulus was increased in 3-dB steps from the level used in
      experiment 1. Modulation of interaural correlation alone proved to have a flat
      psychometric function. The functions for NoS pi and for combined monaural and
      binaural cues appeared similar in slope, but shifted horizontally. The results
      indicate that for sentence materials, neither fluctuations in interaural
      correlation nor in monaural intensity are sufficient to support speech
      recognition at signal-to-noise ratios where 50% intelligibility is achieved in
      the NoS pi configuration; listeners appear to synergistically combine monaural
      and binaural information in this task, to some extent within the same frequency
      region.

PMID- 16454310
TI  - Perceptual similarity of regional dialects of American English.
AB  - Previous research on the perception of dialect variation has measured the
      perceptual similarity of talkers based on regional dialect using only indirect
      methods. In the present study, a paired comparison similarity ratings task was
      used to obtain direct measures of perceptual similarity. Naive listeners were
      asked to make explicit judgments about the similarity of a set of talkers based
      on regional dialect. The talkers represented four regional varieties of American
      English and both genders. Results revealed an additive effect of gender and
      dialect on mean similarity ratings and two primary dimensions of perceptual
      dialect similarity: geography (northern versus southern varieties) and dialect
      markedness (many versus few characteristic properties). The present findings are
      consistent with earlier research on the perception of dialect variation, as well
      as recent speech perception studies which demonstrate the integral role of talker
      gender in speech perception.

PMID- 16454311
TI  - Differentiation of speech and nonspeech processing within primary auditory
      cortex.
AB  - Primary auditory cortex (PAC), located in Heschl's gyrus (HG), is the earliest
      cortical level at which sounds are processed. Standard theories of speech
      perception assume that signal components are given a representation in PAC which
      are then matched to speech templates in auditory association cortex. An
      alternative holds that speech activates a specialized system in cortex that does
      not use the primitives of PAC. Functional magnetic resonance imaging revealed
      different brain activation patterns in listening to speech and nonspeech sounds
      across different levels of complexity. Sensitivity to speech was observed in
      association cortex, as expected. Further, activation in HG increased with
      increasing levels of complexity with added fundamentals for both nonspeech and
      speech stimuli, but only for nonspeech when separate sources (release
      bursts/fricative noises or their nonspeech analogs) were added. These results are
      consistent with the existence of a specialized speech system which bypasses more
      typical processes at the earliest cortical level.

PMID- 16454312
TI  - Perceived speech rate: the effects of articulation rate and speaking style in
      spontaneous speech.
AB  - In this study, the effect of articulation rate and speaking style on the
      perceived speech rate is investigated. The articulation rate is measured both in
      terms of the intended phones, i.e., phones present in the assumed canonical form,
      and as the number of actual, realized phones per second. The combination of these
      measures reflects the deletion of phones, which is related to speaking style. The
      effect of the two rate measures on the perceived speech rate is compared in two
      listening experiments on the basis of a set of intonation phrases with carefully
      balanced intended and realized phone rates, selected from a German database of
      spontaneous speech. Because the balance between input-oriented (effort) and
      output-oriented (communicative) constraints may be different at fast versus slow
      speech rates, the effect of articulation rate is compared both for fast and for
      slow phrases from the database. The effect of the listeners' own speaking habits
      is also investigated to evaluate if listeners' perception is based on a
      projection of their own behavior as a speaker. It is shown that listener
      judgments reflect both the intended and realized phone rates, and that their
      judgments are independent of the constraint balance and their own speaking
      habits.

PMID- 16454313
TI  - First-language phonotactics in second-language listening.
AB  - Highly proficient German users of English as a second language, and native
      speakers of American English, listened to nonsense sequences and responded
      whenever they detected an embedded English word. The responses of both groups
      were equivalently facilitated by preceding context that both by English and by
      German phonotactic constraints forced a boundary at word onset (e.g., lecture was
      easier to detect in moinlecture than in gorklecture, and wish in yarlwish than in
      plookwish). The American L1 speakers' responses were strongly facilitated, and
      the German listeners' responses almost as strongly facilitated, by contexts that
      forced a boundary in English but not in German (thrarshlecture, glarshwish). The
      German listeners' responses were significantly facilitated also by contexts that
      forced a boundary in German but not in English (moycelecture, loitwish), while L1
      listeners were sensitive to acoustic boundary cues in these materials but not to
      the phonotactic sequences. The pattern of results suggests that proficient L2
      listeners can acquire the phonotactic probabilities of an L2 and use them to good
      effect in segmenting continuous speech, but at the same time they may not be able
      to prevent interference from L1 constraints in their L2 listening.

PMID- 16454314
TI  - Beamformer performance with acoustic vector sensors in air.
AB  - For some time, compact acoustic vector sensors (AVSs) capable of sensing particle
      velocity in three orthogonal directions have been used in underwater acoustic
      sensing applications. Potential advantages of using AVSs in air include
      substantial noise reduction with a very small aperture and few channels. For this
      study, a four-microphone array approximating a small (1 cm3) AVS in air was
      constructed using three gradient microphones and one omnidirectional microphone.
      This study evaluates the signal extraction performance of one nonadaptive and
      four adaptive beamforming algorithms. Test signals, consisting of two to five
      speech sources, were processed with each algorithm, and the signal extraction
      performance was quantified by calculating the signal-to-noise ratio (SNR) of the
      output. For a three-microphone array, robust and nonrobust versions of a
      frequency-domain minimum-variance (FMV) distortionless-response beamformer
      produced SNR improvements of 11 to 14 dB, and a generalized sidelobe canceller
      (GSC) produced improvements of 5.5 to 8.5 dB. In comparison, a two-microphone
      omnidirectional array with a spacing of 15 cm yielded slightly lower SNR
      improvements for similar multi-interferer speech signals.

PMID- 16454315
TI  - Rainforests as concert halls for birds: are reverberations improving sound
      transmission of long song elements?
AB  - In forests reverberations have probably detrimental and beneficial effects on
      avian communication. They constrain signal discrimination by masking fast
      repetitive sounds and they improve signal detection by elongating sounds. This
      ambivalence of reflections for animal signals in forests is similar to the
      influence of reverberations on speech or music in indoor sound transmission.
      Since comparisons of sound fields of forests and concert halls have demonstrated
      that reflections can contribute in both environments a considerable part to the
      energy of a received sound, it is here assumed that reverberations enforce also
      birdsong in forests. Song elements have to be long enough to be superimposed by
      reflections and therefore longer signals should be louder than shorter ones. An
      analysis of the influence of signal length on pure tones and on song elements of
      two sympatric rainforest thrush species demonstrates that longer sounds are less
      attenuated. The results indicate that higher sound pressure level is caused by
      superimposing reflections. It is suggested that this beneficial effect of
      reverberations explains interspecific birdsong differences in element length.
      Transmission paths with stronger reverberations in relation to direct sound
      should favor the use of longer signals for better propagation.

PMID- 16454316
TI  - Vocal behavior of resident killer whale matrilines with newborn calves: the role
      of family signatures.
AB  - Studies of the vocal behavior of resident killer whales or orcas, Orcinus orca,
      in British Columbia have shown that matrilines have unique call repertoires
      consisting of up to 17 different call types. These call types cannot be
      attributed exclusively to specific behaviors, and their function in social
      contexts is poorly understood. This study investigated the change in call
      patterns of three resident matrilines in a changed social environment, before and
      up to one year after the birth of a calf. Acoustic data were collected with a
      network of hydrophones and were supplemented by visual observations. Call use
      changed distinctly after the birth of a calf in all three observed matrilines.
      All call types that were recorded in control situations were also recorded in
      postbirth situations; however, aberrant versions of discrete calls and excitement
      calls made up a higher proportion of calls after birth. Most conspicuously,
      family-specific call types occurred significantly more frequently in the days
      following a birth in two of the three matrilines and gradually returned to
      prebirth values within 2 weeks. Their increased use after a calf's birth may
      facilitate the learning process of this "acoustic family badge" and thereby help
      to recognize and maintain cohesion with family members.

PMID- 16454317
TI  - Monaural and binaural hearing directivity in the bottlenose dolphin: evoked
      potential study.
AB  - Hearing thresholds as a function of sound-source azimuth were measured in
      bottlenose dolphins using an auditory evoked potential (AEP) technique. AEP
      recording from a region next to the ear allowed recording monaural responses.
      Thus, a monaural directivity diagram (a threshold-vs-azimuth function) was
      obtained. For comparison, binaural AEP components were recorded from the vertex
      to get standard binaural directivity diagrams. Both monaural and binaural
      diagrams were obtained at frequencies ranging from 8 to 128 kHz in quarter-octave
      steps. At all frequencies, the monaural diagram demonstrated asymmetry
      manifesting itself as: (1) lower thresholds at the ipsilateral azimuth as
      compared to the symmetrical contralateral azimuth and (2) ipsilateral shift of
      the lowest-threshold point. The directivity index increased with frequency: at
      the ipsilateral side it rose from 4.7 to 17.8 dB from 11.2 to 128 kHz, and from
      10.5 to 15.6 dB at the contralateral side. The lowest-threshold azimuth shifted
      from 0 degrees at 90-128 kHz to 22.5 degrees at 8-11.2 kHz. The frequency
      dependent variation of the lowest-threshold azimuth indicates the presence of two
      sound-receiving apertures at each head side: a high-frequency aperture with the
      axis directed frontally, and a low-frequency aperture with the axis directed
      laterally.

PMID- 16454318
TI  - Automated categorization of bioacoustic signals: avoiding perceptual pitfalls.
AB  - Dividing the acoustic repertoires of animals into biologically relevant
      categories presents a widespread problem in the study of animal sound
      communication, essential to any comparison of repertoires between contexts,
      individuals, populations, or species. Automated procedures allow rapid,
      repeatable, and objective categorization, but often perform poorly at detecting
      biologically meaningful sound classes. Arguably this is because many automated
      methods fail to address the nonlinearities of animal sound perception. We present
      a new method of categorization that incorporates dynamic time-warping and an
      adaptive resonance theory (ART) neural network. This method was tested on 104
      randomly chosen whistle contours from four captive bottlenose dolphins (Tursiops
      truncatus), as well as 50 frequency contours extracted from calls of transient
      killer whales (Orcinus orca). The dolphin data included known biologically
      meaningful categories in the form of 42 stereotyped whistles produced when each
      individual was isolated from its group. The automated procedure correctly grouped
      all but two stereotyped whistles into separate categories, thus performing as
      well as human observers. The categorization of killer whale calls largely
      corresponded to visual and aural categorizations by other researchers. These
      results suggest that this methodology provides a repeatable and objective means
      of dividing bioacoustic signals into biologically meaningful categories.

PMID- 16454319
TI  - In vitro ultrasonic characterization of human cancellous femoral bone using
      transmission and backscatter measurements: relationships to bone mineral density.
AB  - Thirty-eight slices of pure trabecular bone 1-cm thickness were extracted from
      human proximal femurs. A pair of 1-MHz central frequency transducers was used to
      measure quantitative ultrasound (QUS) parameters in transmission [normalized
      broadband ultrasound attenuation (nBUA), speed of sound (SOS)] and in backscatter
      [broadband ultrasound backscatter (BUB)]. Bone mineral density (BMD) was measured
      using clinical x-ray quantitative computed tomography. Site-matched identical
      region of interest (ROIs) of 7 x 7 mm2 were positioned on QUS and QCT images.
      This procedure resulted in 605 ROIs for all the specimens data pooled together.
      The short-term precision of the technique expressed in terms of CV was found to
      be 2.3% for nBUA, 0.3% for SOS and 4.5% for BUB. Significant linear correlation
      between QUS and BMD were found for all the 605 ROIs pooled, with r2 values of
      0.73, 0.77, and 0.58 for nBUA, SOS, and BUB, respectively (all p < 0.05). For the
      BUB, the best regression was obtained with a polynomial fit of second order (r2 =
      0.63). An analysis of measurements errors was developed. It showed that the
      residual variability of SOS is almost completely predicted by measurements
      errors, which is not the case for BUA and BUB, suggesting a role for micro
      architecture in the determination of BUA and BUB.

PMID- 16454320
TI  - Oral manifestations and analysis of salivary and blood urea levels of patients
      under going haemo dialysis and kidney transplant.
AB  - AIM AND OBJECTIVES: To evaluate oral manifestations in patients with renal
      diseases and to correlate blood and salivary urea levels in patients undergoing
      haemodialysis and kidney transplant. MATERIAL AND METHODS: Study group subjects
      were selected from patients undergoing hemodialysis and patients who had
      underwent kidney transplant. Adequate history was recorded. All the groups were
      examined extra orally and intra orally and findings were recorded. SAMPLE
      COLLECTION: Venous blood was collected from the antecubital fossa in control
      group. In patients with renal disease undergoing dialysis, blood was
      collectedjust prior to the dialysis. Renal transplant patients' blood samples
      were collected during review visit. Unstimulated saliva was collected and
      submitted to the laboratory immediately for urea examination by an automated
      analyzer. RESULTS: Extra oral manifestations like swollen face, pale skin, pedal
      edema, and bruises on the skin, nausea and vomiting in nearly 50% of the patiens,
      and oral manifestations like uraemic odour, dry mouth, and altered taste
      sensation were noted. There was a correlation between blood urea and salivary
      urea concentration in patients under going hemodialysis and kidney transplant.
      CONCLUSION: Saliva can be used as a non-invasive diagnostic tool.

PMID- 16454321
TI  - Characterisation and quantification of mucosal vasculature in oral submucous
      fibrosis.
AB  - AIM: Quantitative assessment of the mucosal vascularity in oral sub mucous
      fibrosis (OSF) by image analysis using OPTIMAS ver 6.0 software. The vascularity
      was assessed by estimating (a) the mean vascular density, (b) the mean vascular
      area percentage, and (c) the mean vascular luminal diameter. SUBJECT AND METHODS:
      Twenty (20) OSF and ten (10) age and sex matched healthy volunteers comprised the
      study group. The 5 microm thick H and E stained mucosal sections were examined
      and quantified in an image analyzer for number, size, density of vessels, and
      percentage of vascular area using an area morphometry tool. ANOVA is used to test
      equality of several means without affecting Type 1 error. RESULT: The mean
      vascular density is found to be more or less same in the test and control samples
      (F = 0.82, P>0.05). The mean vascular percentage area shows an increasing trend
      as the disease progresses (F = 8.63, p<0.01). The mean vascular luminal diameter
      also shows an increasing trend as the disease progresses (F = 34.1, p<0.001).
      CONCLUSION: The usual tissue reaction resultant to ischaemia / hypoxia does not
      seem to operate in this disease, which is preconditioned by significant stromal
      changes as part of the disease process. The mean vascular dilatation noted is
      assumed to be an adaptive response to compensate tissue ischaemia/hypoxia.

PMID- 16454322
TI  - In vitro pulp chamber temperature rise during composite resin polymerization with
      different curing lights.
AB  - The damaging effect of temperature increase on the pulp tissue during restorative
      treatment has been a matter of concern in dentistry for many years. Aesthetic
      restorative dentistry relies on polymerization of light-activated resin
      composites which can cause damaging effects to the dental pulp as a result of
      temperature rise caused by both the exothermic reaction process and the energy
      absorbed during irradiation. This in vitro study was carried out to measure the
      increase in pulp chamber temperature induced during composite resin
      polymerization with various light curing units in three different and common
      clinical situations (Veneer, Class II, Class III) and the clinical implications
      of the results. Measurement of pulp temperature changes during polymerization was
      performed with a Al-Cr Thermocouple positioned at the pulp-dentin junction. Mean
      values were calculated from six measurements with each light curing unit.

PMID- 16454323
TI  - Variations of the location of the greater palatine foramina in dry human skulls.
AB  - Seventy-one adult skulls (58 dentulous skulls: 56 bilateral and 2 unilateral, 13
      edentulous: 11 bilateral and 2 unilateral) of unknown sex were examined for the
      variations of the location of the greater palatine foramen. The location of
      greater palatine foramen (GPF) was noted with relation to mid sagittal suture
      (MSS), posterior palatal border (PPB), and maxillary molars by measuring the
      distances using a sliding caliper to the nearest millimeter. Difference in the
      distance of the foramen from MSS and PPG in both the skull types was found to be
      statistically insignificant. Commonest location of the foramen was found to be
      opposite to third molar tooth (85.95%), followed by the interval between second
      and third molar teeth (13.15%), and opposite to the second molar tooth (only one
      case - 0.88%). Well-formed bony canals were found along the groove for the
      palatine nerves and vessels unilaterally in the right side in two skulls. These
      observation may be of help to the dental surgeon during the peripheral block of
      maxillary nerve for the maxillo-facial surgery.

PMID- 16454324
TI  - Periodontal diseases and awareness among patients.
AB  - Awareness of periodontal problems and how they interpret this and their timely
      intervention affects periodontal health. Many people neither recognize the
      symptoms of periodontal disease nor do they associate existing symptoms with the
      disease. Hence one should ensure that the routes of science transfer are open so
      that the appropriate knowledge regarding the prevention and control of
      periodontal diseases are available to the public.

PMID- 16454325
TI  - Carpal tunnel syndrome: survey of an occupational hazard.
AB  - Carpal tunnel syndrome (CTS) is one of a number of muscle-tendon and nerve
      related disorders that affect people performing intensive work with their hands.
      Hand and wrist disorders are receiving most of the attention although their
      symptoms are reported less often by dental workers than symptoms of neck/back
      disorders. The lack of data pertaining to the behaviour of Indian general dental
      practitioners towards carpal tunnel syndrome was the basis behind this
      descriptive study to evaluate the prevalence of carpal tunnel syndrome symptoms.

PMID- 16454326
TI  - Prosthetic rehabilitation of individuals with ectodermal dysplasia.
AB  - Ectodermal dysplasia is a genetic disorder commonly affecting the development of
      teeth. The quality of life of the affected individuals can be improved by a
      multidisciplinary approach to the treatment plan. The treatment may include
      removable, fixed, implant-supported prostheses, or a combination of these
      options. This case report describes in detail the diagnosis and treatment of two
      such individuals using removable overdentures.

PMID- 16454327
TI  - Florid cemento-osseous dysplasia.
AB  - Cemento-osseous dysplasia is probably the most common fibro-osseous lesion
      encountered in clinical practice. It is thought to be a reactive phenomenon that
      arises from elements within the periodontal ligament. Here we present a case of
      37-year-old female patient, who reported for a regular dental check-up.
      Incidentally, mixed radiopaque-radiolucent lesions were found bilaterally in the
      radiograph. Based on the clinical examination and radiographic evaluation, we
      arrived at a diagnosis of florid cemento-osseous dysplasia.

PMID- 16454328
TI  - Hospital periodontal surgery.
AB  - Phenytoin-induced gingival overgrowth is a recognized side effect in many
      cerebral palsy patients using diphenyl hydantoin for the control of seizures.
      Severe gingival overgrowth in these patients can affect normal masticatory
      function, lead to poor occlusal development, and compromise esthetics. This
      report addresses the complex nature of treating phenytoin-induced gingival
      overgrowth in a mentally retarded 20-year-old female patient. For this patient,
      full-mouth gingivectomy procedure was performed under general anesthesia in a
      single session. Post operative follow-up was uneventful. This article discusses
      major indications, contraindications, and protocols to be followed for
      periodontal surgical procedures done under general anesthesia.

PMID- 16454329
TI  - [The individual differences in responses of cancer patient blood cells on
      radiation treatment during the chemotherapy].
AB  - A comparative comet-assay study of X-ray influence on DNA of leukocytes of
      peripheral blood from both cancer patients in the course of chemotherapy and on
      healthy donors was carried out. The amount of DNA registered in comet tails of
      blood samples from 18 healthy donors was between 0.8-3.6%. The mean value was 2.9
      +/- 0.5%. In the preparations of cancer patients, an increase in comet tail DNA
      was observed for each chemotherapy course and in each subsequent course compared
      to the previous one. The individual variations were found in the level of DNA
      damage in the response to the administration of cyclophosphane, of methotrexate,
      of 5-fluorourocil (CMF protocol). The X-ray radiation (4 Gy) challenge test of
      blood cells showed an increase in comet tail DNA, the dynamics of radiation
      induced lesions varying between individuals. The combined use of X-ray radiation
      and of the comet-assay in evaluating the capacity of the defence systems of the
      whole blood cells during chemotherapy let us to hold the monitoring of the state
      of genome of leukocytes without their isolation. This approach enables additional
      information on leukocyte genome to be rapidly obtained.

PMID- 16454330
TI  - [The diagnostic of membranes' state after exposure of gamma-radiation of small
      doses].
AB  - There are the results of experimental research of the change of membranes'
      conditions under the action of gamma-radiation using the method of following
      membranes' electroporation of the accurate impulse of the electrical field for
      the analysis of defects after the action of gamma-radiation. As of the research
      material the suspension of erythrocytes was used. It was shown that the velocity
      of decreasing of the erythrocytes in the case of combined action of gamma
      radiation and the impulse of the electrical field is more than the sum of such
      velocities in the case of the action of the factors separately. The method of the
      electroporation of the accurate impulse of the electircal field is obvious for
      the practicaland the analytical research of membranes' defects.

PMID- 16454331
TI  - [The radiobiologycal approaches of the individual prognosis of the radiotherapy
      efficacy of the tumor deseases].
AB  - The results of several years standing investigations about the develop of the way
      to the individual prognosis of tumour sensitivity to radiotherapy are brought.
      The initial level of proliferative activity of different tumour types of
      individual patients--carcinoma of oropharingeal zone, stomach, oesophagys,
      rectum, glioblastoma have been studied. It was shown that for the several tumours
      the high initial level of proliferative activity is the indication of good
      prognosis. For the all tumours studied the significant decreasing of
      proliferative activity in the beginning of the radiation treatment is the good
      prognostic factor of tumour regression (decreasing of volume on 70-100%) or the
      strong damages of tumour tissue (III-IV grade of patomorphosis). The data of
      literature of last years are discussed and the proposal is that for the
      determination of prognostic factors the multiparameter analysis is need.

PMID- 16454332
TI  - [The efficiency of the radiobiological and clinical of the intraoperative
      radiation therapy in combination with distant gamma-radiation therapy of
      malignant tumors].
AB  - The efficiency of the radiobiological and the clinical planning of the
      combination of the intraoperative radiation therapy (IORT) and the external beam
      radiation therapy (EBRT) was assessed according to the incidence of local
      recurrences and to the level of radiation-induced damages during 5 years for
      patients with malignant tumors of head and neck, lung and soft tissues. Criteria
      of radiobiological planning for performing IORT + EBRT using the modified model
      of TDF (time-dose-fractionation) for calculating a single IORT dose and total
      radiation doses was defined among 169 patients of the studied group. The control
      group included 115 patients who were treated with surgery followed by photon
      radiation therapy at the total dose of 40-45 Gy. The Clinical critetia for
      performing the combined treatment with IORT and EBRT were such like: locally
      advanced tumors, multicentrical location of tumor sites and the necessity of the
      increasing of the total doses of the combination of IORT and EBRT. The Average
      rates of total doses of IORT and EBRT were 67 +/- 2.1 Gy for patients with cancer
      of nasal cavity and of accessory nasal sinus, 50 +/- 1.8 Gy for patients with
      oral cavity cancer, 60 +/- 0.7 Gy for patients with lung cancer and 75 +/- 2.0 Gy
      for patients with sarcomas of soft tissues. Radiation-induced damages for normal
      tissues such as mandible osteomyelitis, neuritis and pathological bone fracture
      occurred among 16.8% of patients from the studied group if the TDF factor was
      exceeded over 100 conventional units. The combined treatment with IORT and EBRT
      resulted the significant reduction of recurrence rate among 5-year as compared
      with the combined treatment fot the control group: 37.5 +/- 5.3% and 65 +/- 5.1%
      of patients with cancer of nasal cavity and accessory nasal sinus; 55.8 +/- 6.3%
      and 80 +/- 5.9% of patients with oral cavity cancer; 57.8 +/- 6.7% and 75 +/-
      5.8% of patients with non-small cell lung cancer and 32.7 +/- 6.1% and 72 +/-
      6.7% of patients with sarcomas of soft tissues, respectively. The use of criteria
      for radiobiological and clinical planning of the combined treatment with IORT and
      EBRT promotes the improvement of long-term treatment results.

PMID- 16454333
TI  - [Heavy particle beams (proton) in oncology (35-year practice of N.N. Blokhin
      Cancer Research Centre)].
AB  - Clinically proved "alternative breast-preserving method" applicable for patients
      with locally advanced nodal breast cancer. These patients refuse to go in to
      surgery or have indications for surgery (183 patients--T(1-4)N(0-3)M(0-1)). This
      method consists of the combination of the traditional method of the whole breast
      and/or nodal photon irradiation with local highly concentrated proton irradiation
      in the dosage iso-equivalent to tumor (proton with energy from 130 to 180 MeV,
      with stop in the target in notice depth). We used the irradiation of the
      adenohypophysis with narrow proton beams energy 200 MeV. The aim of the first
      combination of the components is the selectively influence on the target and the
      channeling to the tumor and its subclinical substances the dosages sufficient for
      the total irradiation of tumor with sparing surrounding tissues and parts of
      body. The goal of irradiation of adenohypophysis with protons is the
      normalization of its hormonal activity and elimination of factors stimulating
      growth of tumor cells in case of dishormonal cancer. The suggested method didu't
      only improve the results of the treatment of locally advanced breast cancer, but
      also contributed to the reducing of the emotional stress. We received high
      results of the patients with locally advanced nodal breast cancer of criteria:
      local control rate (96%), long remission (more then 40%) and 5-year actuarial
      survival rate (83%). The patients examined during 5 and 18 years. It made a good
      cosmetic effect and high quality life of the patients with breast cancer.

PMID- 16454334
TI  - [The estimation of the perspectives of the 1,3,4-thiadiazine derivatives as the
      protectors means for the health tissues under radiation therapy of malignant
      tumour patients].
AB  - We generalized the results of our own researches of the mechanisms, determined
      the high (90% BALB-line mice were survived) radioprotection activity by 1,3,4
      thiadiazine derivatives. It was determined that this preparat achieves the
      highest concentrations in the critical for the acute radiation influence tissues.
      The preparate bind with the cell's membranes, nucleus and mitochondries, blockade
      the development of the radial reactions on the tissues level. Small quantity
      passes to the brain marrow, takes part in the regulative processes, which central
      nervous system is produced, reduces the metabolitical processes in the organism.
      It doesn't possess the election accumulation in the tumour and it is perspective
      for the prevention of damage health tissues under irradiation cancroid's therapy.

PMID- 16454335
TI  - [The long-term effects of the radiation action and induced genome instability].
AB  - The intensive studies of the long-term effects of the radiation on human and
      animal cells allowed to reveal the row of new positions in the radiobiology and
      the genetics. One of the example is the determination of the fact that the
      genetic effects of the radiation action are not limited by the alterations
      detectable directly after the corresponding influences. It was found that this
      and other genome alterations (the chromosome and the gene mutations,
      transformation the reproductive cell death, the changes of the radiosensitivity
      and others) can appear de novo in it's sufficiently remote generations of the
      surviving cells. They differ in the spectrum and in the intensity from acute
      influence results and now unite with notion "induced genome instability". These
      discoveries made the studies of the regularities and of the mechanisms of forming
      of the genome instability in the whole organism of the human and animals more
      active. In this review about radiation induced instability of genome data are
      systematized in the accordance with the objects of the study: cultivated cells in
      vitro-->posterity of laboratory animals-->children born from irradiated parents-
      >adult people in the remote periods after irradiation.

PMID- 16454336
TI  - [About the peculiar form of radiation induced genome instability].
AB  - The usually studied forms of the induced genome instability manifested as a
      steady change of mutability of proliferated cells, we compared with its peculiar
      form characterized by the inherited irreversible increase of the level of
      spontaneous damage of cells. These effects appear of the moment of reaching of
      the dose threshold according to the "all or nothing" principle, just after the
      relatively low-dose radiational action. These changes occur without association
      with the cell division and thereby have an exclusive significance in the
      pathogenesis of the radiational damage of low-renewing mammalian tissues. It is
      suggested that the considered changes could underlie the development of the
      delayed non-cancerogenic somatic postradiational sequelae and of the acceleration
      of natural aging.

PMID- 16454337
TI  - [The intellectual development of the children exposed to the influence of the
      ionizing radiation].
AB  - The mental development level of the children living in the territories polluted
      by the radioactive nuclide as the result of Cheernobil power plant damage,
      exposed to the prenatal irradiation, evacuated from the alienation zone, born
      from parents-liquidators (1st generation of the irradiated people) was evaluated.
      177 children were examinated. The control group included 34 children not exposed
      to the radiation. The complex of psychometric methods--"D. Wexler children's
      intellectual test"--for 3-6-year-old children in the translation and adaptation
      of A.U. Panasyuk was applied for evaluating the intellect rate. In the structure
      of the observed groups the pathology diseases of nervous system, of digestion
      organs and the congenital anomalies prevailed. Clinical and instrumental
      investigation showed no differences in the neurology status between the observed
      and the control groups. It was proved that the intellect of the children exposed
      to the radiation corresponds the age standards. However, intellectual development
      of the children irradiated in the prenatal period and children evacuated from the
      2nd zone of radioactive pollution (or living there) has a tendency to its
      decreasing. The determining role of social, of economic and of biologic factors
      (the parents' education, the region of living, the birth weight) in the intellect
      development was indicated.

PMID- 16454338
TI  - [The retrospective cytogenetic dosimetry using the results of conventional
      chromosomal analysis in Chernobyl clean-up workers].
AB  - The paper presents the results of the cohortal biodosimetry carried out in 435
      Chernobyl clean-up workers, who were surveyed with the conventional cytogenetic
      technique in terms from several days to 10 years after the end of their duties in
      the Chernobyl accident exclusive zone. An empirical model of the aberrant cell
      dynamics was utilized for the calculation of mean initial yields of dicentrics
      and centric rings in groups with different terms and duration of staying in the
      Chernobyl zone. Corresponding protracted irradiation doses estimated from
      aberration levels ranged from 79 to 670 mGy. The probabilistic distribution of
      the radiation doses was constructed by the applying the Bayesian analysis to
      initial individual chromosome exchange yields extrapolated to the exposure
      termination moment. This distribution was characterized by the mean dose about
      460 mGy and maximum of probability density in the interval of 50-300 mGy. For the
      late somatic risk assessment in clean-up workers the probabilistic distribution
      of equivalentally-acute radiation doses was proposed; that had the mean value
      about 270 mGy, modal classes of 250-350 mGy and 99.8% of the probability density
      concentrated within the dose range from 0 to 1000 mGy.

PMID- 16454339
TI  - [The adaptive reactions in hemopoietic system of the irradiated mice of two
      lines, differing in the level of emotionally-stress reactions on the emotional
      stress].
AB  - On lines of the mice genetically differing on the sensitivity on emotional stress
      (steady--of the mouse of the line C57BL/6 or sensitive--of the mouse of the line
      BALB/c), the research of the development of the adaptive reactions in the system
      of the blood on the emotional stress influencing animals on the background of the
      preliminary irradiation in a low dose (0.9 Gy) is carried out. The unirradiated
      mice of the line C57BL/6 adequately reacted on the stress, that was shown in a
      moderate behavioural reaction during the period of stress, and the development of
      high-grade adaptive reactions in the hemopoietic system. Among the mice of the
      line C57BL/6 in conditions of the combined influence of ionizing radiation and of
      the emotional stress was not revealed of the infringements of the adaptive
      reactions of the hemogenesis. As opposed to these data, among unirradiated mice
      of the line BALB/c the sharply expressed behavioural reactions during the stress
      were marked, that was accompanied by incomplete development of the adaptive
      reactions in the system of a blood on the stress. Under the influence of stress
      on the previously irradiated animal line BALB/c was observed the inhibition of
      the medullar hemopoiesis.

PMID- 16454340
TI  - [The effect of prodigiozan on the postradiational recovery of hemopoiesis in long
      term bone morrow cultures of mice of different genotypes].
AB  - The influence of prodigiozan on the processes of postirradiation recovery of
      hemopoiesis in long-term bone morrow cultures of two strain mice, having genetic
      distinctions in the condition of systems of the reparation DNA was investigated.
      It was showh, that the irradiation of long-term bone morrow cultures of mice
      reparation-defective strain 101/H resulted in the greater degree damage of early
      haemopoietic precursors (GM-CFC), reduction of the amount of the immature and of
      the mature granulocytes and of the decrease of the number of stromall cells in
      the comparison with the bone morrow of reparation-capable mice (CBA x C57B1)F1.
      Under the introduction in cultures of prodigiozan for 24 hours prior to an
      radiation the distinctions of the speed of postirradiation recovery of
      hemopoiesis substantially smoothed out, and the protective effect of the drag in
      bone morrow cultures of mice 101/H was comparable to those, marked in bone morrow
      cultures of reparation-capable strain mice (CBA x C57B1)F1. It is supposed, that
      this effect can be caused by the activation of the hematopoietic microenvironment
      cellular elements and inclusion of the mechanisms of intercellular of
      interactions, which provide stimulation of the regenerative processes at action
      radioprotective drags and can in the certain degree to compensate the defect of
      the systems of the reparation DNA.

PMID- 16454341
TI  - [The electromagnetic fields of the base stations of mobile radio communication
      and ecology. The characteristic and the estimation of the electromagnetic
      condition around the base station of mobile radio communication].
AB  - Below is submitted the characteristic of the electromagnetic condition around the
      base stations, which bases on our own data. The hygienic estimation was
      considered.

PMID- 16454342
TI  - [The electromagnetic fields of the base stations of mobile radio communication
      and ecology. The estimation of danger of the base station EMF for population and
      for bioecosystems].
AB  - The estimation of the danger for the population and for the bioecosistems of the
      electromagnetic conditions around of the base stations was given. The
      insufficiency of the scientific knowledge does not allow to guarantee the safety
      of the population and of the bioecosystems in the conditions of a round-the-clock
      long-term influence of EMF RF. WHO recommends to use "Precautionary principle".

PMID- 16454343
TI  - [The damage of the neural retina and of the retinal pigment epithelium of eyes of
      rats exposed to highly intensive visible light under alloxanic diabetes].
AB  - The experiments on white mongrel rats showed that the light with the intensity of
      6000 1x lasting for 6 hours resulted the destruction of the retinal pigment
      epithelium, of the internal and the external neurosensory cellular processes with
      subsequent nuclei piknosis and radial glia replacement. On the 7th day after
      exposure to light focal effusion of the retina corresponding layers. Under the
      irradiation in diabetes the amount of cells with karyopyknosis increases in 1.6
      times in comparision with the findings in case free of diabetes. Was found, that
      the alloxanic diabetes in its early stage increases the light impairment of the
      neurosensory cells of the retina.

PMID- 16454344
TI  - [The ecology-genetic consequences of chronic irradiation for the populations of
      the plants and animals].
AB  - The modem presentations are considered in the review about the consequences for
      the genotype of animals and of plants of the chronic action of factors of low
      intensity. Inoffer is spoken about possible dug the chronic irradiation in small
      doses in microevolution events.

PMID- 16454345
TI  - [The peculiarities of separate and combined exposure to low dose-rate gamma
      radiation and 232Th nitrate on thyroid gland].
AB  - We studied the effects of both: of the separate and of the combined exposure to
      gamma-radiation (absorbed doses for 30 days were 1.4-1.8 cGy, for 90 days were
      4.3-5.4 cGy) and 232Th nitrate (in concentrations 6.0; 20.0 and 60.0 mg/l) on the
      CBA line mice thyroid gland. Hat is shown the thyroid gland response to the
      combined exposure is significant in an appearance of non-linear effects of
      interaction. The intensiveness of the radiation influence (time and doses) is
      revealed to affect on the biological response direction in thyroid gland. The
      intensity of this effect was depended on the correlation between the radiation
      activity and the chemical components concentration. The dispersive analyses
      showed that all the studied factors caused structural changes in thyroid gland in
      this experiment, but the gamma-radiation influence causes the primary
      contribution.

PMID- 16454346
TI  - A role of the choroid plexus in transplantation therapy.
AB  - The choroid plexuses (CPs) play pivotal roles in the most basic aspects of neural
      function. Some of the roles of the CP include maintaining the extracellular
      milieu of the brain by actively modulating chemical exchange between the CSF and
      brain parenchyma, surveying the chemical and immunological status of the brain,
      detoxifying the brain, secreting a nutritive "cocktail" of polypeptides, and
      participating in repair processes following trauma. This diversity of functions
      suggests that even modest changes in the CP can have far reaching effects.
      Indeed, changes in the anatomy and physiology of the CP have been linked to
      several CNS diseases. It is also possible that replacing diseased CP or
      transplanting healthy CP might be useful for treating acute and chronic brain
      diseases. Here we describe the wide-ranging functions of the CP, alterations of
      these functions in aging and neurodegeneration, and recent demonstrations of the
      therapeutic potential of transplanted CP for neural trauma.

PMID- 16454347
TI  - Minimal focal steatosis of liver after islet transplantation in humans: a long
      term study.
AB  - Several reports have been published on islet transplantation in humans, but few
      data are available on the effect of islet infusion on the hepatic structure. Our
      aim was to evaluate in a longitudinal study the impact on the liver of
      intrahepatic islet transplantation. Clinical outcome and liver imaging were
      evaluated in 31 cases of islet-kidney transplantation (follow-up 38 +/- 4 months,
      range 12-96 months). Patients were divided into three groups: full function (FF,
      9 cases: established insulin independence); partial function (PF, 16 cases:
      transient insulin independence, prolonged C-peptide secretion): no function (NF,
      6 cases: exhaustion of C-peptide secretion within the first year). Upper abdomen
      sonogram was regularly performed during the whole follow-up period. Percutaneous
      liver biopsy was performed in case of echographic abnormalities. Multiple small
      areas of focal hyperechogenicity were observed in nine cases after 6-12 months.
      These findings were observed only in FF (two) and in PF (seven) patients. Fasting
      C-peptide levels at the time of echography were higher in negative than in
      positive patients (2.42 +/- 0.16 vs. 1.51 +/- 0.10 ng/ml, p = 0,0001). Liver
      biopsies showed focal macrovesicular steatosis, surrounded by normal liver
      parenchyma. Normal liver function was maintained. In conclusion, our results
      indicate that islet transplantation can lead to structural changes of the liver
      parenchyma (focal steatosis). It is more often observed in patients with partial
      function. Sonogram can be considered a specific method to reveal liver changes
      after islet transplantation.

PMID- 16454348
TI  - Generation of islet-like hormone-producing cells in vitro from adult human
      pancreas.
AB  - Transplantation of pancreatic islets can provide long-lasting insulin
      independence for diabetic patients, but the current islet supply is limited. Here
      we describe a new in vitro system that utilizes adult human pancreatic islet
      enriched fractions to generate hormone-producing cells over 3-4 weeks of culture.
      By labeling proliferating cells with a retrovirus-expressing green fluorescent
      protein, we show that in this system hormone-producing cells are generated de
      novo. These hormone-producing cells aggregate to form islet-like cell clusters.
      The cell clusters, when tested in vitro, release insulin in response to glucose
      and other secretagogues. After transplantation into immunodeficient, nondiabetic
      mice, the islet-like cell clusters survive and release human insulin. We propose
      that this system will be useful as an experimental tool for investigating
      mechanisms for generating new islet cells from the postnatal pancreas, and for
      designing strategies to generate physiologically competent pancreatic islet cells
      ex vivo.

PMID- 16454349
TI  - AN69 hollow fiber membrane will reduce but not abolish the risk of transmission
      of porcine endogenous retroviruses.
AB  - As the risk of porcine endogenous retrovirus (PERV) infection is a major obstacle
      to the xenotransplantation of porcine tissue, we investigated whether an AN69
      hollow fibre membrane, used for islets of Langerhans transplantation, could
      prevent the transfer of PERVs and thus reduce the risk of PERV infection. PK15
      cells were used as a PERV source. A specific and highly sensitive RCR was used
      for detection of a PERV provirus DNA (gag region) and a porcine mtDNA. Human U293
      cells were incubated in vitro with encapsulated PK15 cells, concentrated
      encapsulated PK15 supernatant, or concentrated PK15 supernatant as a control. CD1
      mice were implanted in vivo with encapsulated PK15 cells or injected with PK15
      supernatant. We found no infection in human cells incubated with either
      encapsulated PK15 supernatant or in 10 out of 11 samples after coincubation with
      encapsulated PK15 cells. Infection of human cells was, however, detected in 1 out
      of 11 samples after coincubation with encapsulated PK15 cells. The presence of
      PERV provirus DNA and porcine mtDNA was detected in all the investigated tissues
      of the mice injected with PK15 supematant and in various tissues of the mice
      implanted with encapsulated PK15 cells. Four weeks after the last injection of
      PK15 supernatant or a fiber explantation, no mouse showed any presence of PERV
      provirus DNA or porcine mtDNA. Our results demonstrate that AN69 hollow fiber
      membrane will reduce but not abolish the risk of PERV infection. Because the real
      risk of PERV infection still remains unknown, it is necessary to investigate
      further the real protection that could be provided by hollow fibers to ensure the
      safety of clinical xenotransplantation.

PMID- 16454350
TI  - Effective islet isolation method with extremely high islet yields from adult
      pigs.
AB  - Achieving good islet isolation is one of the most important factors for
      successful islet transplantation. Porcine pancreas is suitable for islet
      isolation research due to its anatomical and physiological similarities to human
      pancreas. In this study, we evaluated a new porcine islet isolation method
      designed to maximize islet yield and compared it with our previous open pan
      method and the standard method using a Ricordi chamber (Ricordi method). We
      performed 15 porcine islet isolations, five each with the new method, the open
      pan method, and the Ricordi method. The new method features several important
      improvements. Pancreata remain uncut and are kept intact during collagenase
      intraductal injection, a large filtration chamber to handle whole pancreata, low
      concentration of collagenase (Liberase HI) for digestion, and large plastic
      containers for large-scale islet purification. All isolated islets were assessed
      for yield, purity, viability and in vitro function. Islets isolated with this new
      method were transplanted under the kidney capsules of SCID mice with chemically
      induced diabetes for in vivo functional assessment (n = 8). With the new method,
      we obtained on average more than 1,000,000 islet equivalents (IE) (1,236,266 +/-
      213,486 IE) (mean +/- SE) before purification and 800,000 IE (879,815 +/- 222,729
      IE) after purification from one adult pig. Islet yield per pancreas was
      significantly higher compared with our previous open pan method (30,666 +/-
      11,532 IE, p < 0.01) and the Ricordi method (317,073 +/- 86,093 IE, p < 0.05).
      All mice, transplanted with 1000 islets from the new method, returned to
      normoglycemia within 4 days after transplantation. Our new method makes it
      possible to obtain extremely high porcine islet yield with good function. It
      should produce useful information for human islet isolation and transplantation,
      and might be applied to single donor clinical xenogeneic transplantation.

PMID- 16454351
TI  - The effects of bone marrow-derived mesenchymal stem cells and fascia wrap
      application to anterior cruciate ligament tissue engineering.
AB  - After an anterior cruciate ligament (ACL) injury, surgical reconstructions are
      necessary in most cases, either with autografts, allografts, or artificial
      ligaments. Potential tissue-engineered ligaments would circumvent the
      disadvantages apparent in these methods. While seeding of mesenchymal stem cells
      (MSCs) and fascia wrap could potentially improve tissue regeneration and
      mechanical properties, their exact roles were evaluated in the current study.
      Knitted biodegradable scaffolds of poly-L-lactic acid (PLLA) and poly-glycolic
      lactic acid (PGLA) yarns were used to reconstruct ACL in 48 rabbits. These were
      divided into four equal groups: only knitted scaffolds were used in group I;
      knitted scaffolds and mesenchymal stem cells were used in group II; knitted
      scaffolds, MSCs, and fascia lata were used in group III; knitted scaffolds and
      fascia lata were used in group IV. Carboxyfluorescein diacetate (CFDA)-labeled
      MSCs were used to trace the fate of seeded cells in groups II and III. Histology,
      Western blot analysis, and mechanical properties of reconstructed ACL were
      analyzed after 20 weeks. Fibroblast ingrowths were seen in all four groups while
      CFDA-labeled MSCs could be found after 8 weeks of implantation in groups II and
      III. Both the amount of collagen type I and collagen type III in groups III and
      IV were significantly higher than in group II, which was much higher than in
      group I. Both maximal tensile loads and stiffness of the reconstructed ACLs in
      groups I, II, III, and IV were significantly lower than normal controls after 20
      weeks of implantation. It is concluded that MSCs could promote synthesis of
      collagen type I and collagen type III in tissue-engineered ligaments, while
      fascia wraps have stronger effects. Both MSC seeding and fascia wrap could not
      enhance ultimate tensile load and stiffness.

PMID- 16454352
TI  - Analysis of allogeneic and syngeneic bone marrow stromal cell graft survival in
      the spinal cord.
AB  - Bone marrow stromal cells (MSC) are attractive candidates for developing cell
      therapies for central nervous system (CNS) disorders. They can be easily
      obtained, expanded in culture, and promote modest functional recovery following
      transplantation into animal models of injured or degenerative CNS. While
      syngeneic MSC grafts can be used efficiently, achieving long-term survival of
      allogeneic MSC grafts has been a challenge. We hypothesize that improved graft
      survival will enhance the functional recovery promoted by MSC. To improve MSC
      graft survival, we tested two dosages of the immune suppressant cyclosporin A
      (CsA) in an allogeneic model. Syngeneic transplantation of MSC where cells
      survive well without immune suppression was used as a control. Sprague-Dawley
      rats treated with standard dose (n = 12) or high-dose (n = 12) CsA served as
      allogeneic hosts; Fisher 344 rats (n = 12) served as syngeneic hosts. MSC were
      derived from transgenic Fisher 344 rats expressing human placental alkaline
      phosphatase and were grafted into cervical spinal cord. Animals treated with
      standard dose CsA showed significant decreases in allograft size 4 weeks
      posttransplantation; high CsA doses yielded significantly better graft survival 4
      and 8 weeks posttransplantation compared to standard CsA. As expected, syngeneic
      MSC transplants showed good graft survival after 4 and 8 weeks. To investigate
      MSC graft elimination, we analyzed immune cell infiltration and cell death.
      Macrophage infiltration was high after 1 week in all groups. After 4 weeks, high
      dose CsA and syngeneic animals showed significant reductions in macrophages at
      the graft site. Few T lymphocytes were detected in any group at each time point.
      Cell death occurred throughout the study; however, little apoptotic activity was
      detected. Histochemical analysis revealed no evidence of neural differentiation.
      These results indicate that allogeneic transplantation with appropriate immune
      suppression permits long-term survival of MSC; thus, both allogeneic and
      syngeneic strategies could be utilized in devising novel therapies for CNS
      injury.

PMID- 16454353
TI  - Purified human bone marrow multipotent mesenchymal stem cells regenerate
      infarcted myocardium in experimental rats.
AB  - Recent findings suggest the feasibility of cardiac repair by transplantation of
      bone marrow mesenchymal stem cell (MSCs). However, it remains controversial
      regarding which cell type is the best source for transplanting into the ischemic
      heart because of lack of well-defined cell markers. In this study, we
      investigated the in vitro and in vivo effects of the novel multipotent marrow
      mesenchymal stem cells (MMSCs) from human bone marrow. Pluripotent markers (Oct4,
      Bmi1, and Abcg2) and vascular endothelial growth factor (VEGF) were detected by
      RT-PCR and immunofluorescence in MMSCs. Myocardial differentiation was induced in
      the expanded MMSC cultures by treatment with 5-azacyline. Expressions of VEGF in
      the animals transplanted with MMSCs were markedly increased in comparison with
      the animals injected with fibroblasts or saline at both mRNA and protein levels.
      VEGF expression was observed in both transplanted MMSCs and recipient
      cardiomyocytes by immunofluorescence. Confocal immunofluorescence microscopy
      revealed the specific markers for cardiomyocytes and endothelial cells in
      transplanted MMSCs 14 days after transplantation. Vessel count was increased and
      left ventricular function improved post-MMSC transplantation. These results
      indicate that transplantation of purified MMSCs from human bone marrow
      upregulated VEGF expression, enhanced angiogenesis, and improved the functional
      recovery following myocardial infarction in rats.

PMID- 16454354
TI  - Protection of photoreceptor cells from phototoxicity by transplanted retinal
      pigment epithelial cells expressing different neurotrophic factors.
AB  - Transplantation of cells or tissues and the intravitreal injection of
      neurotrophic factors are two methods that have been used to treat retinal
      diseases. The purpose of this study was to examine the effects of combining both
      methods: the transplantation of retinal pigment epithelial (RPE) cells expressing
      different neurotrophic factors. The neutrophic factors were Axokine, brain
      derived-neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF).
      The enhanced green fluorescence protein (eGFP) gene was used as a reporter gene.
      These genes were transduced into RPE cells by lipofection, selected by
      antibiotics, and transplanted into the subretinal space of 108 rats. The rats
      were examined at 1 week and 3 months after the transplantation to determine
      whether the transduced cells were present, were expressing the protein, and were
      able to protect photoreceptors against phototoxicity. The survival of the
      transplanted cells was monitored by the presence of eGFP. The degree of
      protection was determined by the thickness of the outer nuclear layer. Our
      results showed that the degree of photoreceptor protection was different for the
      different types of neurotrophic factors at 1 week. After 3 months, the number of
      surviving transplanted cell was markedly reduced, and protection was observed
      only with the BDNF-transduced RPE cells. A significant degree of rescue was also
      observed by BDNF-transduced RPE cells in the nontransplanted area of the retina
      at both the early and late times. Lymphocytic infiltration was not detected in
      the vitreous, retina, and choroid at any time. We conclude that the
      transplantation of BDNF-transduced RPE cells can reduce the photoreceptor damage
      induced by phototoxicity in the transplanted area and weakly in the
      nontransplanted area.

PMID- 16454355
TI  - Synergistic effect of keratinocyte transplantation and epidermal growth factor
      delivery on epidermal regeneration.
AB  - Both keratinocyte transplantation and epidermal growth factor (EGF) delivery
      stimulate epidermal regeneration. In this study, we hypothesized that the
      combined therapy of keratinocyte transplantation and EGF delivery accelerates
      epidermal regeneration compared to the single therapy of either keratinocyte
      transplantation or EGF delivery. To test this hypothesis, we utilized fibrin
      matrix as a keratinocyte/EGF delivery vehicle for epidermal regeneration. Full
      thickness wounds were created on the dorsum of athymic mice, and human
      keratinocytes and EGF in fibrin matrix were sprayed onto the wounds to regenerate
      epidermal layers (group 1). As controls, human keratinocytes in fibrin matrix
      (group 2), EGF in fibrin matrix (group 3), or fibrin matrix alone (group 4) was
      sprayed onto the wounds. Spraying keratinocytes suspended in fibrin matrix did
      not affect the keratinocyte viability, as the cell viabilities before and after
      spraying were not different. EGF was released from fibrin matrix for 3 days. The
      wounds were analyzed with histology and immunohistochemistry at 1 and 3 weeks
      after treatments. Compared with the control groups, initial wound closure rate
      was highest in group 1. Histological analyses indicated that group 1 exhibited
      faster and better epidermal regeneration than the other groups.
      Immunohistochemical analyses showed that regenerated epithelium in groups 1 and 2
      stained positively for human involucrin at 3 weeks, whereas the tissue sections
      of the groups 3 and 4 stained negatively. Human laminin was detected at the
      dermal-epidermal junction of the regenerated tissues in groups 1 and 2 at 3 weeks
      and was not detected in groups 3 and 4. The epidermal thickness of the
      regenerated tissues in group 1 was significantly thicker than that of the other
      groups at all time points. These results suggest that the combined therapy of
      keratinocyte transplantation and EGF delivery is more efficacious for epidermal
      regeneration than each separate therapy alone.

PMID- 16454356
TI  - Differentiation effects by the combination of spheroid formation and sodium
      butyrate treatment in human hepatoblastoma cell line (Hep G2): a possible cell
      source for hybrid artificial liver.
AB  - The aim of this study was to investigate the feasibility of human hepatoblastoma
      cell line (Hep G2), which differentiates by spheroid formation, and treatment
      with sodium butyrate (SB) as a cell source for hybrid artificial liver (HAL). Hep
      G2 spontaneously formed spheroids in polyurethane foam (PUF) within 3 days of
      culture and restored weak ammonia removal activity. Treatment with SB, which is a
      histone deacetylase inhibitor, further increased the ammonia removal activity of
      Hep G2 spheroids in a concentration-dependent manner. The activation of ornithine
      transcarbamylase--a urea cycle enzyme--was significantly related to the
      upregulation of ammonia removal by spheroid formation, but scarcely contributed
      to the further upregulation following SB treatment. In contrast with ammonia
      removal, treatment with SB reduced the albumin secretion of Hep G2 spheroids in a
      concentration-dependent manner. In the PUF-HAL module in a circulation culture,
      the ammonia removal rate and albumin secretion rate (per unit volume of the
      module) of Hep G2 spheroids treated with 5 mM SB were almost the same as those of
      primary porcine hepatocyte spheroids. These results suggest that simultaneous use
      of spheroid formation and SB treatment in Hep G2 is beneficial in enhancing the
      functions of human hepatocytes with potential applications in regenerative
      medicine and drug screening.

PMID- 16454357
TI  - The effect of simulated microgravity by three-dimensional clinostat on bone
      tissue engineering.
AB  - Evidence suggests that mechanical stress, including gravity, is associated with
      osteoblast differentiation and function. To examine effects of microgravity on
      bone tissue engineering, we used a three-dimensional (3D) clinostat manufactured
      by Mitsubishi Heavy Industries (Kobe, Japan). A 3D clinostat is a device that
      generates multidirectional G force. By controlled rotation on two axes, it
      cancels the cumulative gravity vector at the center of the device. We cultured
      rat marrow mesenchymal cells (MMCs) in the pores of interconnected porous calcium
      hydroxyapatite (IP-CHA) for 2 weeks in the presence of dexamethasone using the 3D
      clinostat (clinostat group). MMCs cultured using the 3D clinostat exhibited a 40%
      decrease in alkaline phosphatase activity (a marker of osteoblastic
      differentiation), compared with control static cultures (control group). SEM
      analysis revealed that although there was no difference between the two groups in
      number or distribution of cells in the pores, the clinostat group exhibited less
      extensive extracellular matrix formation than the control group. Cultured IP
      CHA/MMC composites were then implanted into subcutaneous sites of syngeneic rats
      and harvested 8 weeks after implantation. All implants showed bone formation
      inside the pores, as indicated by decalcified histological sections and
      microfocus computed tomography. However, the volume of newly formed bone was
      significantly lower for the clinostat group than for the control group,
      especially in the superficial pores close to the implant surface. These results
      indicate that new bone formation in culture was inhibited by use of the 3D
      clinostat, and that this inhibition was mainly due to suppression of osteoblastic
      differentiation of MMCs.

PMID- 16454358
TI  - Influence of preservation solution on the isolation and culture of human
      hepatocytes from liver grafts.
AB  - A major problem for the isolation and transplantation of hepatocytes is the lack
      of resources for obtaining viable hepatocytes. Improving this situation would
      enhance hepatic cell transplantation programs. Our objective was to evaluate the
      influence of the preservation solutions used during organ retrieval on the
      quality of hepatocytes isolated from liver tissue. We compared the results of the
      collagenase perfusion technique for isolation of hepatocytes in human livers
      flushed with University of Wisconsin (UW) and Celsior preservation solutions.
      Yield (number of viable cells per gram of tissue), cellular viability, efficiency
      of cells to attach to culture plates and form a monolayer, and drug metabolizing
      competence of the hepatocytes were measured. Successful isolation was achieved in
      63% of the procedures using the UW solution and 100% of the procedures using the
      Celsior solution. In the UW group, significantly lower cell viability (38 +/- 41%
      vs. 79 +/- 14%, p < 0.05), yield of cells (4.0 +/- 5.2 x 10(6) vs. 8.2 +/- 5.6 x
      10(6) cells/g, p < 0.05), and protein content at 24 h of culture (0.6 +/- 0.6 vs.
      1.2 +/- 0.3 mg protein per plate, p < 0.05) than in Celsior solution were found.
      However, similar values of P450 activities were found in both groups. The more
      successful isolation, better yield, and higher cell viability obtained from human
      liver grafts preserved in Celsior solution, in comparison to UW solution, suggest
      Celsior solution as the most appropriate for preserving cadaveric hepatic tissue
      to be used for hepatocyte harvesting.

PMID- 16454359
TI  - Large-scale isolation of human hepatocytes for therapeutic application.
AB  - During the last decade, hepatocyte transplantation has been suggested as a safe
      and potentially effective clinical option for the treatment of acute or
      decompensating chronic liver failure as well as for hereditary liver disease.
      Currently, one of the major limiting factors for clinical application is the
      insufficient access to suitable liver cell preparations. In cooperation with the
      German and Catalane organ procurement organizations, a routine procedure for the
      isolation of hepatocytes from donor organs rejected for transplantation (n = 117)
      has been established. The process is performed according to the current EC
      Guidelines for Good Manufacturing Practice (cGMP) and all corresponding national
      laws and regulations concerning donor organ and tissue procurement. In about 50%
      of the cases (n = 58) the three-step perfusion procedure has been completed with
      an average total cell yield of 5.9 x 10(9) cells per organ, the cell preparations
      displaying a mean viability of 64%. The mean specific yield was 3.6 x 10(6) total
      and 2.6 x 10(6) viable cells per gram liver tissue, respectively. Specific cell
      yields from three infantile donor livers were considerably higher. No correlation
      between isolation efficiency and cold ischemia time or donor age was found within
      the adult organ donors. In contrast, organs with a severe steatosis generally did
      not result in successful cell isolation. Results of sterility and endotoxin
      determination are also presented. In summary, a standardized and cGMP conform
      method of hepatocyte isolation from nontransplantable liver organs was
      established, which reproducibly yields large amounts of hepatocytes suitable for
      therapeutic application.

PMID- 16454360
TI  - Stem Cells and Development publishes neural stem cells compendium.

PMID- 16454361
TI  - Effects of copper and cross-linking on the extracellular matrix of tissue
      engineered arteries.
AB  - In many cases, the mechanical strengths of tissue-engineered arteries do not
      match the mechanical strengths of native arteries. Ultimate arterial strength is
      primarily dictated by collagen in the extracellular matrix. but collagen in
      engineered arteries is not as dense, as organized, or as mature as collagen in
      native arteries. One step in the maturation process of collagen is the formation
      of hydroxylysyl pyridinoline (HP) cross-links between and within collagen
      molecules. HP cross-link formation, which is triggered by the copper-activated
      enzyme lysyl oxidase, greatly increases collagen fibril stability and enhances
      tissue strength. Increased cross-link formation, in addition to increased
      collagen production, may yield a stronger engineered tissue. In this article, the
      effect of increasing culture medium copper ion concentration on engineered
      arterial tissue composition and mechanics was investigated. Engineered vessels
      grown in low copper ion concentrations for the first 4 weeks of culture, followed
      by higher copper ion concentrations for the last 3 weeks of culture, had
      significantly elevated levels of cross-link formation compared to those grown in
      low copper ion concentrations. In contrast, vessels grown in high copper ion
      concentrations throughout culture failed to develop higher collagen cross-link
      densities than those grown in low copper ion concentrations. Although the
      additional cross-linking of collagen in engineered vessels may provide collagen
      fibril stability and resistance to proteolysis, it failed to enhance global
      tissue strength.

PMID- 16454362
TI  - The Terri Schiavo case in a comparative perspective.

PMID- 16454363
TI  - Terri Schiavo: the assessment of the persistent vegetative state in accordance
      with German law.
AB  - The case of Terri Schiavo in the USA served to intensify the debate in Germany
      which itself had in part already been characterised by fundamentalism. Now that
      some time has elapsed and the political debate has quietened, this case is to be
      taken up again in discussing the permissibility and the prerequisites of passive
      euthanasia for patients in a persistent vegetative state. A short reconstruction
      of the facts of the case (II) is to be followed by a survey of the case law of
      the Criminal Panels (III) which is essential to understand the present legal
      policy debate to be discussed at a later stage (IV).

PMID- 16454364
TI  - Substituting a judgment of best interests: dignity and the application of
      objective principles to PVS cases in the U.K.
AB  - The melee that surrounded the last days of Terri Schiavo's life was reminiscent
      of a classical Greek tragedy. Much like Antigone, Ms. Schiavo became enmeshed in
      irresistible and opposite forces, resolved to use her situation as an arena for
      the determination of political and legal issues as diverse as the exercise of
      states' rights, the extent of individual rights, the role of the judiciary, the
      re-opening of the abortion debate, and the regulation of stem cell research. As
      Europeans watched the drama unfold, the forces at play in the United States
      clashed head-on, in a rhetorically inflammatory spectacle which, on this side of
      the Atlantic, left many aghast. Most unsettling was the prospect of individuals
      wielding the power of state and national legislatures in what was, ultimately, an
      intensely personal affair. In the United Kingdom, the struggle was a stark
      reminder of the differences, not only between British and American political
      culture, but between our approaches to legal issues which present themselves at
      the end of life. The existence of well-established procedures and principles, and
      the extensive involvement of neutral third parties and the courts in pursuit of
      an objective determination of an individual patient's 'best interests', are key
      to the conclusion that Terri Schiavo's case would have been handled at least as
      effectively and efficiently as it was by the courts in Florida and the United
      States. That issues of consent and capacity can be determined by British courts
      on the basis of generally applicable principles leads to the subsequent
      conclusion that a 'best interests' determination leaves significantly less scope
      for conflict than the individualistic, much more personal and determinative
      construct of the 'substituted judgment' test in the United States.

PMID- 16454365
TI  - Withdrawing life support from patients in a persistent vegetative state: the law
      in the Netherlands.
AB  - This article sets out how a case like that of ms. Schiavo is likely to be decided
      in a Dutch court and compares that with the law in the United States. In the
      Netherlands there is one case with striking similarities: the decision of the
      Arnhem Court of Appeal of 1989. After describing that case (which to a large
      extent still reflects the legal state of the art), comments are given on several
      aspects of the issue, such as the labelling of artifical feeding as a medical
      intervention, the role of the physician, the position of the proxy or surrogate,
      the ways to resolve dispute in case of conflict, and the significance of advance
      directives. The analysis will show that, although there is more consensus on the
      issue now than there was 16 years ago, there are still several questions that
      need to be addressed in the future.

PMID- 16454366
TI  - The Data Protection (Amendment) Act, 2003: the Data Protection Directive and its
      implications for medical research in Ireland.
AB  - Directive 95/46/EC on the Protection of Individuals with regard to the Processing
      of Personal Data and on the Free Movement of Such Data has been transposed into
      national law and is now the Data Protection (Amendment) Act, 2003. The Directive
      and the transposing Act provide for new obligations to those processing data. The
      new obligation of primary concern is the necessity to obtain consent prior to the
      processing of data (Article 7, Directive 95/46/EC). This has caused much concern
      especially in relation to 'secondary data' or 'archived data'. There exist, what
      seem to be in the minds of the medical research community, two competing
      interests: (i) that of the need to obtain consent prior to processing data and
      (ii) the need to protect and foster medical research. At the same time as the
      introduction of the Act, other prior legislation, i.e. the Freedom of Information
      Act, 1997-2003, has encouraged candour within the doctor-patient relationship and
      the High Court in Ireland, in the case of Geoghegan v. Harris, has promulgated
      the 'reasonable-patient test' as being the correct law in relation to the
      disclosure of risks to patients. The court stated that doctors have a duty to
      disclose all material risks to patients. The case demonstrates an example of a
      move toward a more open medical relationship. An example of this rationale was
      also recently seen in the United Kingdom in the House of Lords decision in
      Chester v. Afshar. Within the medical research community in Ireland, the need to
      respect the autonomy of patients and research participants by providing
      information to such parties has also been observed (Sheikh A. A., 2000 and Irish
      Council for Bioethics, 2005). Disquiet has been expressed in Ireland and other
      jurisdictions by the medical research communities in relation to the exact
      working and meaning of the Directive and therefore the transposing Acts (Strobl
      et al). This may be due to the fact that, as observed by Beyleveld "The Directive
      makes no specific mention of medical research and, consequently, it contains no
      provisions for medical research as an explicitly delineated category." (Beyleveld
      D., 2004) This paper examines the Irish Act and discusses whether the concerns
      expressed are well-founded and if the Act is open to interpretation such that it
      would not hamper medical research and public health work.

PMID- 16454367
TI  - Free movement of medical doctors: the new Directive 2005/36/EC on the recognition
      of professional qualifications.

PMID- 16454368
TI  - European Court of Human Rights. ECHR 2005/14 Case of Ostrovar v. Moldova, 13
      September 2005, no. 35207/03 (fourth section).

PMID- 16454369
TI  - European Court of Human Rights. ECHR 2005/15 Case of Maurice v. France, 6 October
      2005, no. 11810/03 (Grand Chamber).

PMID- 16454370
TI  - Narrating the right to sexual well-being and the global management of misery:
      Maria Rosa Henson's Comfort Woman and Charlene Smith's Proud of Me.

PMID- 16454371
TI  - Disregarding the suffering of others: narrative, comedy, and torture.

PMID- 16454372
TI  - Accumulated lives: metaphor, materiality, and the homes of the elderly.

PMID- 16454373
TI  - Journeying with the "stone": Montaigne's healing Travel Journal.

PMID- 16454374
TI  - From speechlessness to narrative: the cases of Holocaust historians and of
      psychiatrically hospitalized survivors.

PMID- 16454375
TI  - Holocaust video testimony, oral history, and narrative medicine: the struggle
      against indifference.

PMID- 16454376
TI  - Interventional narratology: form and function of the narrative medical write-up.

PMID- 16454377
TI  - A theology of illness: Franz Kafka's "A Country Doctor".

PMID- 16454378
TI  - Transparency in publications.

PMID- 16454379
TI  - An ethicist's commentary on the client who wants a placebo.

PMID- 16454380
TI  - Histopathologic lesions of diabetes mellitus in a domestic ferret.
AB  - A 2-year-did ferret was referred with a diagnosis of diabetes mellitus. The
      animal died despite insulin therapy and was submitted for necropsy. Light
      microscopic examination revealed a mild hepatic lipidosis and pancreatic lesions
      consisting of a diffuse vacuolation of the Langerhans' islet cells with a
      periodic acid-Schiff positive material compatible with glycogen.

PMID- 16454381
TI  - Feline immunodeficiency virus testing in stray, feral, and client-owned cats of
      Ottawa.
AB  - Feline immunodeficiency virus (FIV) seroprevalence is evaluated in 3 groups of
      cats. Seventy-four unowned urban strays were tested, as well as 20 cats from a
      small feral cat colony, and 152 client-owned cats. Of the 246 cats tested, 161
      (65%) were male and 85 (35%) were female. Seroprevalence for FIV was 23% in the
      urban strays, 5% in the feral cat colony, and 5.9% in the client-owned cats. Ten
      cats (4%) were also positive for Feline leukemia virus (FeLV) antigen, including
      2 cats coinfected with FeLV and FIV. Seroprevalence for FIV in cats from Ottawa
      is similar to that found in other nonrandom studies of cats in North America.

PMID- 16454382
TI  - Stall dimensions and the prevalence of lameness, injury, and cleanliness on 317
      tie-stall dairy farms in Ontario.
AB  - The study objectives were to provide a province-wide description of stall
      dimensions and the aspects of cattle welfare linked to stall design in the tie
      stall industry. Data on stall design; stall dimensions; and the prevalence of
      lameness, injury, and hind limb and udder cleanliness in lactating dairy cattle
      were collected from a sample of 317 tie-stall farms across Ontario. The majority
      of the study farms (90%) had stalls with dimensions (length, width, tie-chain
      length, and tie rail height) that were less than the current recommendations.
      This may explain, in part, the prevalence of lameness measured as the prevalence
      of back arch (3.2%) and severe hind claw rotation (23%), hock lesions (44%), neck
      lesions (3.8%), broken tails (3%), dirty hind limbs (23%), and dirty udders
      (4.6%). Veterinarians and producers may use this information to compare farms
      with the industry averages and target areas in need of improvement.

PMID- 16454383
TI  - Monensin toxicosis in a dairy herd.
AB  - An acute onset of illness was reported in a lactating dairy herd in Canada in
      which monensin had been incorporated in error in its ration at almost 10 times
      the prescribed level. All of the lactating cows became lethargic, were
      inappetant, developed diarrhea, and had decreased milk production from 28
      kg/cow/day, the day before exposure, to 23 kg/cow/day, 3 d later. Within 9 d, all
      animals recovered from the incident and milk production returned to previous
      levels.

PMID- 16454384
TI  - Specificity dependence between serological tests for diagnosing bovine
      brucellosis in Brucella-free farms showing false positive serological reactions
      due to Yersinia enterocolitica O:9.
AB  - When brucellosis false positive serological reactions happen in cattle, the
      serial use of pairs of specificity-correlated serological tests (rose bengal,
      complement fixation, competitive ELISA) results in specificities lower than
      expected. In this situation, highly specific tests, such as the indirect ELISA
      used alone, may be more adequate than serial testing.

PMID- 16454385
TI  - Treatment of an ocular squamous cell carcinoma in a stallion with atrial
      fibrillation.
AB  - A stallion was presented for surgical treatment of limbal squamous cell
      carcinoma. Excision with a conjunctival pedicle flap was done to prevent ocular
      invasion and preserve vision. A complication was the diagnosis of atrial
      fibrillation, which was not converted to sinus rhythm due to the potential
      complication of treatment with quinidine sulfate.

PMID- 16454386
TI  - Pemphigus erythematosus in a chow chow.
AB  - A 3.5-year-old, spayed female, chow chow presented with a pruritic, ulcerative,
      butterfly lesion on the nasal planum, typical of the pemphigus complex. Pemphigus
      erythematosus was diagnosed by histopathologic examination. Treatment consisted
      of enrofloxacin and immunosuppressive therapy with prednisone and azathioprine.
      Within 5 wk of treatment, the lesions had resolved almost completely.

PMID- 16454387
TI  - Good stuff for joints!

PMID- 16454388
TI  - Anaplasmosis, animal welfare, and bilateral trade between Canada and the USA.

PMID- 16454389
TI  - Terminal bond problems.

PMID- 16454390
TI  - Lamb hemoglobinuria due to nutritional hypophosphatemia.

PMID- 16454391
TI  - Diagnostic dermatology. Demodicosis.

PMID- 16454392
TI  - Problem-solving clinical audit: a vehicle for improving the quality of hospital
      care.

PMID- 16454393
TI  - Mortality in children admitted to Port Moresby General Hospital: how can we
      improve our hospital outcomes?
AB  - A detailed audit, part retrospective and part prospective, of deaths occurring in
      children admitted to the children's wards of the Port Moresby General Hospital
      over a 12-month period was made. 238 children died out of the 4898 admitted, an
      overall case fatality rate of 4.9%, with a monthly range of 3.7%-9.6%. The
      proportion of deaths approximated the proportion of admissions in each age group.
      92% of the children had a weight of less than 80% of the standard weight for age
      and 30% weighed less than 60% of the standard weight for age. 24 (11%) of the
      deaths occurred within the first 6 hours of admission, 39 (17%) within the first
      12 hours and 58 (26%) within the first 24 hours. 89 children (40%) died more than
      one week after admission. Pneumonia, meningitis, measles and septicaemia were the
      four leading certified causes of death and paediatric AIDS was the fifth. Less
      than half of the deceased children were appropriately immunized for their age. 27
      deaths (12%) were assessed as preventable. 150 (67%) were classified as from
      treatable causes but unavoidable, 18 (8%) from untreatable causes, 22 (10%) of
      undetermined cause and 34 (15%) avoidable. The factors associated with avoidable
      deaths were delayed treatment (20 children), inadequate treatment (8 children),
      incorrect treatment (1 child) and others (5 children). Infant and child mortality
      could be reduced by general measures such as improving community nutrition and
      immunization status and improving care-seeking behaviour. Hospital-related
      measures to reduce mortality include improving the accuracy and effectiveness of
      triage and provision of adequate staffing levels and bed space. Periodic in-depth
      audit is necessary to assess quality of patient care, to identify problems and to
      point towards their solution. Accurate recordkeeping is essential for appropriate
      audit and planning.

PMID- 16454395
TI  - In search of pigbel: gone or just forgotten in the highlands of Papua New Guinea?
AB  - Throughout the 1960s and 1970s, pigbel (enteritis necroticans) was the most
      common cause of death in children over the age of 1 year in hospitals in the
      highlands of Papua New Guinea (PNG). There has been recent widespread perception
      that after the successful vaccination program in the 1980s the disease virtually
      disappeared. A new vaccine is now available, but disease burden information is
      conflicting: despite almost no pigbel being reported from major hospitals there
      have been many reports of the disease from outlying health centres. This study
      aimed to provide information on the disease burden of pigbel in PNG, so that
      appropriate vaccine policy decisions could be made. We conducted a 12-month
      prospective study of all cases of acute abdomen in children presenting to 38
      health facilities, 29 health centres and 9 hospitals in the highlands. Children
      were eligible for inclusion if they were aged 1-12 years and had abdominal pain
      of less than 2 weeks' duration. A standardized case definition of pigbel was used
      to distinguish cases of acute abdominal pain very likely to be due to pigbel from
      cases very likely to be accounted for by other diagnoses (such as
      gastroenteritis, typhoid, dysentery, intussusception, urinary tract infection and
      others). A total of 119 cases of acute abdomen were reported from 17 of the 38
      health facilities involved. Of these 119 cases 11 met the criteria for pigbel and
      a further 8 were probable cases. There were 4 deaths among the 119 children with
      acute abdomen: 2 from definite pigbel, 1 from probable pigbel and the other due
      to complications of measles. In 2002 pigbel was the cause of between 9% and 16%
      of presentations with acute abdominal pain in children in the PNG highlands. The
      overall disease burden of pigbel was relatively small (19 definite or probable
      cases and 3 deaths in 12 months). However, there was substantial geographical
      clustering of cases: more than 50% of the definite cases occurred in children
      living within three electorates on the Western Highlands-Enga provincial border,
      no more than 40 km from each other. This study will be useful in planning pigbel
      vaccine policy and future surveillance.

PMID- 16454394
TI  - Therapeutic efficacy of chloroquine or amodiaquine in combination with
      sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Papua New
      Guinea.
AB  - Resistance of Plasmodium falciparum to chloroquine is widespread in Papua New
      Guinea. At a meeting in Port Moresby in October 1997, it was decided to explore a
      possible change of the current first-line treatment of uncomplicated malaria with
      chloroquine alone (amodiaquine for children under five years) to chloroquine or
      amodiaquine in combination with sulfadoxine-pyrimethamine (S-P). To assess the
      therapeutic efficacy of the new drug combination in Papua New Guinea, a study was
      carried out in 1998-1999 at five hospital outpatient departments. From the 513
      patients enrolled for the study, 95 defaulted from follow-up. Of the remaining
      418, 399 (95.5%) had an adequate clinical response (ACR). Out of the 19 patients
      who did not have an ACR, 3 (0.7% of the total) developed severe signs in the
      first 24 hours and were treated in hospital; they were regarded as early
      treatment failures. The remaining 16 did not complete the study on the basis of
      various exclusion criteria but were not excluded from the analysis. From these
      results it was concluded that the combination was effective and a decision was
      taken in May 2000 to introduce the two-drug combination regimens as the standard
      first-line treatment of uncomplicated malaria, including falciparum malaria, in
      Papua New Guinea.

PMID- 16454396
TI  - The aetiology of severe anaemia among antenatal patients of the Port Moresby
      General Hospital.
AB  - Between October 1998 and September 2000, 111 consecutive pregnant patients
      admitted to the Port Moresby General Hospital antenatal ward with a haemoglobin
      level of 6 g/dl or less were studied. The main causes of the severe anaemia were
      as follows: iron deficiency on its own or in combination with another factor 66%-
      iron deficiency on its own 43% and combined folate and iron deficiency 23%--and
      folate deficiency 18%. Malaria was a contributory factor in 13 patients (12%). A
      combination of blood film, bone marrow study, serum assays of ferritin, folate
      and vitamin B12, and mean corpuscular volume (MCV) was used to determine the
      cause of the anaemia. Ferritin levels on their own poorly correlated with the
      presence of iron in the bone marrow. A low MCV correlated well with iron
      deficiency anaemia while a high MCV was associated with folic acid deficiency. It
      would seem therefore that while a bone marrow study is mandatory to reach a
      definitive diagnosis of severe anaemia, MCV, in conjunction with the red cell
      morphology on blood film, would be a good marker for iron and folic acid
      deficiency anaemia, especially as we do not have serum assays readily available
      for folate, ferritin and vitamin B12 in Papua New Guinea.

PMID- 16454397
TI  - Awareness of and attitudes towards HIV among pregnant women at the Antenatal
      Clinic, Port Moresby General Hospital.
AB  - BACKGROUND: The prevalence of HIV (human immunodeficiency virus) among pregnant
      women in Port Moresby has increased tenfold, from 0.08% in 1994 to 0.8% in 2002.
      To stop a further epidemic spread as seen in sub-Saharan Africa it is urgent to
      identify and intervene to reduce risk behaviours. In order to do so it is
      important to evaluate current awareness of and attitude towards HIV. METHODS:
      Interviews with 122 pregnant women were conducted at the Antenatal Clinic, Port
      Moresby General Hospital, Papua New Guinea. We assessed the women's HIV awareness
      and relate the results to education and socioeconomic factors. RESULTS: 4 out of
      122 women did not know about HIV. 97% knew that HIV is spread by sexual contacts,
      96% knew about mother-to-child transmission and 69% knew about infection through
      breastfeeding. However, there were many misconceptions; 36% believed that HIV can
      be spread by mosquitoes and 17% believed that caring for an AIDS (acquired immune
      deficiency syndrome) patient is a risk. Among the women with no education or
      primary school education only, 51% knew for sure that HIV is not spread by caring
      for an AIDS patient, compared to 86% for the women with higher education. 47% of
      the women received their first information about HIV through the media.
      CONCLUSIONS: The AIDS campaigns have been successful in making almost all the
      women aware of HIV as a sexually transmitted disease. However, the high frequency
      of misconceptions makes it probable that patients are stigmatized. This is
      particularly true for the lower educated women. To more effectively fight the HIV
      epidemic it is important to improve the general level of education of both men
      and women, to encourage women to be more in charge of their own sexuality and to
      increase their status in society. It is also important to make men aware of their
      responsibility to practise safe sex.

PMID- 16454398
TI  - The epidemiology of malaria in the Papua New Guinea highlands: 2. Eastern
      Highlands Province.
AB  - The epidemiology of malaria in Eastern Highlands Province (EHP) is characterized
      by generally very low-level or no local malaria transmission but a considerable
      risk of epidemics. In non-epidemic situations, parasite prevalence was under 5%
      in all but one area, Lufa Valley, where P. vivax was the most common parasite
      (prevalence rate of 58%). During epidemics, however, 23% (range 8-63%) of people
      were infected, with P. falciparum the predominant parasite. Mixed infections were
      very common (12%) but P. malariae and P. ovale were rare. Outside epidemics,
      malaria was only a minor source of febrile illness and enlarged spleens and
      anaemia (haemoglobin level < 7.5 g/dl) were virtually absent. However, epidemics
      were associated with a high incidence of relatively severe morbidity, both in
      terms of fevers and moderate to severe anaemia. Epidemic prevention, surveillance
      and response therefore are priorities in malaria control in EHP.

PMID- 16454399
TI  - This will hardly hurt at all!

PMID- 16454400
TI  - [Hundreds of workers killed by VCM].

PMID- 16454401
TI  - [A negatively biased inflexibility may lead into ambiguity].

PMID- 16454402
TI  - [The power of numbers].

PMID- 16454404
TI  - [National Center of Epidemiology, Surveillance and Promotion of Health:
      scientific knowledge for public health].

PMID- 16454403
TI  - [An objection about the conflicts of interest].

PMID- 16454405
TI  - [Why should we publish an atlas of health?].

PMID- 16454406
TI  - [Estimate of potential health benefits of the reduction of air pollution with
      PM10 in Trieste, Italy].
AB  - OBJECTIVES: Estimate of the possible benefits, in Trieste, of a reduction of PM10
      to values not over 60, 50, 40, 30, 20, 10 microg/mc, utilizing data of PM10 of
      the year 2002 as cause specific deaths and admissions. DESIGN: Cause specific
      deaths and admissions attributable to short term effects of PM10 calculated by
      software AirQ, utilizing Relative Risk from MISA 1 study (as published in 2002).
      SETTING: Trieste (Italy). MAIN OUTCOMES MEASURES: Cause specific deaths and
      admissions. RESULTS: Using air pollution data for 2002, 1.8% (CI 95% 0.6%; 2.9%)
      of natural deaths, 2.2% (CI 95% 0.6%; 3.7%) of cardiovascular deaths and 2.5% (CI
      95% 0; 7.3%) of respiratory deaths, 1.5% (CI 95% 0.6; 2.4%) of cardiovascular
      admissions and 1.6% (CI 95% 0; 3.3%) of respiratory admissions were attributable
      to PM10 concentrations over 20 microg/mc. CONCLUSIONS: AirQ software proved to be
      a valid and reliable tool to estimate the potential short term effects of air
      pollution. Special attention is required to choose the relative risks to be
      utilized.

PMID- 16454407
TI  - [Mortality for non-Hodgkin lymphoma and soft-tissue sarcoma in the surrounding
      area of an urban waste incinerator. Campi Bisenzio (Tuscany, Italy) 1981-2001].
AB  - AIM: Aim of the study is to investigate mortality for lymphoematopoietic tumours
      and soft tissue sarcoma of people resident near an urban waste incinerator.
      MATERIALS AND METHODS: We have considered death certificates recorded by National
      Statistical Institute (ISTAT) for the period 1981-2001 of the residents in 277
      municipalities included in a circle of 80 km of radius centered at Campi Bisenzio
      municipality. Mortality data have been analyzed by calendar period (1981-1985,
      1986-1992, 1993-2001) and by specific causes of death. In particular we have
      considered mortality for soft tissue sarcoma and lymphoematopoietic tumours.
      Standardized mortality ratios (SMR) have been evaluated for each calendar period
      using the population of the circle as standard population. RESULTS: Our findings
      point out that males resident in Campi Bisenzio municipality had a higher risk of
      non-Hodgkin lymphoma in the period 1986-1992, with 14 observed cases versus 7.6
      expected (SMR 184.2 CI 90% 111-273). The excess risk is present also for all
      Lymphomas with 18 cases versus 9.07 expected. In the same period, in Campi
      Bisenzio, we observed 2 deaths for soft tissue Sarcoma. CONCLUSION: The study
      shows the presence of a localized cluster of deaths for non-Hodgkin lymphoma, for
      males, in the calendar period 1986-1992. In the same municipality an urban waste
      incinerator was operating from 1973 to 1986, when it was closed following
      evidence of dioxin soil contamination.

PMID- 16454408
TI  - [Analysis of arterial hypertension and work in the epidemiologic study "Aging,
      Health and Work"].
AB  - OBJECTIVE: We evaluated if work conditions or job strain related to professional
      activity or to life styles represent a risk factor for arterial hypertension and
      whether this effect of hypertension is independent of age. DESIGN: through data
      collection of epidemiological inquiries ESTEV and VISAT, applied in Italy on a
      cohort of workers, 32-52 year-old, employed in different productive sectors, we
      analyzed the relationships on working conditions (exposure to certain risks or
      job strain), life styles and self evaluation of health and arterial hypertension.
      Hypertension was considered as SAP > or =160 mm/Hg and/or DAP > or =90 mm/Hg, or
      current antihypertensive treatment. RESULTS: the results refer to 1104 workers,
      76% men and 24% women. Prevalence of hypertension was found to be higher among
      the men than women (33% vs. 22%). Risk estimation in multivariate analysis, by
      logistic regression model, showed a statistically significant association with
      certain work-related factors such as: shift work, awkward posture, standing work,
      doing several tasks contemporarily, being interrupted at work, not being able to
      take eyes off work. The variables referred to cognitive aspects and work
      organization tended to be associated to arterial hypertension even when exposure
      ceased. CONCLUSIONS: both physical and cognitive organisational aspects of work
      are strongly associated with arterial hypertension. The subjective assessment
      that workers give to their work is a relevant element. This aspects should be
      considered as a possible reducible risk factor.

PMID- 16454409
TI  - [Efficacy evaluation of preventive interventions: experience and proposal for
      road accident prevention strategies].
AB  - OBJECTIVE: To supply the local administrators with a tool for a preventive
      evaluation of the improvements in road safety brought about by specific
      interventions which are planned. It is one of the first Italian experiences in
      the area. STUDY DESIGN: The database consists of the accidents occurring in three
      municipalities of the province of Modena characterized by accidents of high
      severity. Models were used to simulate changes related to possible interventions.
      The goodness of the model-based estimates has been evaluated after the
      implementation of interventions. RESULTS: Scenario analyses indicate which
      actions are most effective. Preliminary estimates of efficacy suggest a good
      agreement with model-based forecasts. CONCLUSION: Results encourage the adoption
      of methods of preventive evaluation of the efficacy of preventive actions.

PMID- 16454410
TI  - [Epidemiology of traffic accidents in the province of Trento: first results of an
      integrated surveillance system (MITRIS)].
AB  - OBJECTIVE: Different data sources are available for the surveillance of road
      traffic accidents. Taken separately all have important limits. Therefore the
      integration of medical and non medical data are essential for the construction of
      a surveillance system able to direct preventive and repressive actions. DESIGN:
      Cross sectional study. A computerized system for the rapid and precise
      unification of medical data with data collected by the police force has been
      realized. The model is embedded in a Geographic Information System (WebGIS),
      providing the facility for additional spatial data analysis and modelling. Maps
      of the spatial density of the accidents which consider also the severity of the
      injuries from a medical point of view have been developed. Risk factors
      associated with the severity of the injuries have been evaluated by uni- and
      multivariate statistical analysis. The statistical significance of the
      associations have been tested with Pearson's test. Confidential intervals of the
      Odds ratios were calculated with a probability of 95%. SETTING: Province of
      Trento, Italy. MAIN OUTCOME MEASURES: Number, dynamics and localization of road
      traffic accidents, activity of ambulance services, access to emergency
      departments and hospital admissions RESULTS: For 805/930 injured persons it was
      possible to link the medical data to those collected by the police forces. 111
      (16%) accidents have been classified as severe (with hospital admission) and 694
      as moderate (without hospital admission). The most important risk factors
      associated with the severity are represented by the frontal crash and by being a
      vulnerable road user (pedestrian, cyclist and motorcyclist), specially those <15
      years of age. The classification of the most important sites of road traffic
      accidents in the Trento municipality was significantly modified by the
      integration of the medical data giving more importance to the more dangerous
      sites in terms of severity of the injuries. CONCLUSION: This study shows the
      feasibility of an integrated surveillance of road traffic accidents by using
      routinely collected data on a local basis.

PMID- 16454411
TI  - [Health effects of environmental contamination due to volcanic ash of Mount Etna
      in autumn 2002].
AB  - OBJECTIVE: During autumn 2002 a large eruption of Mount Etna (Sicily, Italy)
      occurred. High levels (over 200 microg/m3) of total suspended particles (PM10)
      were recorded. The aim of the study was to evaluate the acute health effects on
      mortality and hospital admissions in the area around the volcano. DESIGN: Deaths
      and hospital admissions occurring during the eruption period were compared with
      the corresponding figures during the same periods of the previous year (same day
      of the week). Relative risks, RR, and their 95% confidence intervals, CI, were
      computed. Variations in daily hospital admissions for cardiovascular diseases
      associated with daily level of PM10 were estimated. RESULTS: No effects on
      overall and cause-specific mortality were observed during the eruption period.
      Increases were observed in hospital admissions for cardiovascular diseases
      (ischemic diseases: RR 1.31, 95% CI 1.10-1.56; myocardial infarction: RR 1.34,
      95% CI 1.02-1.76) and for cerebrovascular diseases (RR 1.24, 95% CI 1.05-1.47).
      The excesses were stronger among the elderly. Daily admissions for cardiovascular
      diseases were not associated to PM10 levels. CONCLUSION: The effects of the
      eruption of Mount Etna were limited to a temporary increase of cardiovascular
      morbidity, especially among the elderly, possibly as a consequence of stress.

PMID- 16454412
TI  - [Fatality rates of bacterial meningitis from current health databases suggest a
      different case definition. Results of a follow-up study of bacterial meningitis
      in Lazio Region, Italy, 1996-2000].
AB  - OBJECTIVES: To describe mortality and case fatality rate due to bacterial
      meningitis in the Lazio Region from 1996 to 2000, and to compare these estimates
      with those from Cause-of-death Registry (CDR) and Hospital Discharge Registry
      (HDR). METHODS: A follow-up study of mortality was conducted through Registry
      Offices for bacterial meningitis cases reported to surveillance in 1996-2000
      among residents in the Lazio Region. Death due to bacterial meningitis was
      defined as a patient who died during a hospitalization for meningitis or who died
      within 30 days after hospitalization and whose underlying cause of death was
      bacterial meningitis (ICD-9: 036.0, 036.1, 036.2,320.0, 320.1, 320.2, 320.3,
      320.7, 320.8, 320.9, 027.0). Case fatality rates estimated from follow-up study
      were compared with estimates from CDR and HDR of the same period. RESULTS: 525
      bacterial meningitis cases were reported among residents in the whole period; 98
      deaths were detected with a case fatality rate (CFR) of 18.7% (CI 95% 15.4-22.5);
      estimates were higher in patients 64+ year old (44.6%; CI 95% 33.7-55.9) and in
      meningitis due to Streptococcus pneumoniae (27.5%; CI 95% 20.3-35.6) or Listeria
      (32.0%; CI 95% 14.9-53.5). The CFR was 10.1% according to the CDR and 10.9%
      according to the HDR. CONCLUSIONS: CFRs differ according to the database used.
      Differences may be partially due to a selective lower sensitivity in reporting
      deceased cases, but the most important factor seems to be the case definition
      used in follow-up study and other sources of data.

PMID- 16454413
TI  - [Evaluation of the effectiveness of influenza vaccination among the elderly in
      Friuli-Venezia Giulia (Italy)].
AB  - OBJECTIVES: To evaluate the effectiveness of the influenza vaccination in
      reducing medical visits, hospital admissions, and deaths among the population >
      or =65 years of age in Friuli-Venezia Giulia. DESIGN: We conducted a
      retrospective and a prospective cohort study. For the retrospective study, we
      used data from the regional health electronic database. For the prospective
      study, we integrated this source of data with data provided by a sample of
      general practitioners. SETTING: The Friuli-Venezia Giulia region, Northeastern
      Italy. PARTICIPANTS: The population > or =65 years of age assisted by the
      Regional Health Service. MAIN OUTCOME MEASURES: Mortality from any cause, deaths,
      hospital admissions, and medical visits due to influenza, heart disease, and
      respiratory disease, also stratified by age and comorbidity. RESULTS: With the
      exception of some population subgroups, the retrospective study showed that the
      vaccination was not effective in reducing the risk of hospital admission and
      death. On the contrary, the vaccination was associated with an increase in
      hospital admissions due to influenza, heart disease, and respiratory disease
      (increased by 7%, 13%, and 17%, respectively). On the other hand, the prospective
      study showed an association between the vaccination and a 26% reduction in the
      risk of admissions for respiratory disease and a 21% reduction in the risk of all
      cause death, whereas visits due to respiratory disease were increased by 55%.
      CONCLUSIONS: Overall, the influenza vaccination appeared to have a low impact on
      the study cohorts. The vaccination was more effective in subjects <85 years of
      age and in those affected by comorbidity.

PMID- 16454414
TI  - [Traffic injuries in migrants in the territory of the local health Unit n. 13,
      Veneto Region, Italy].
AB  - This paper highlights the importance of using current data systems as generators
      of hypotheses. As an example, we report the analysis of the traffic injuries data
      of the Local Health Unit n. 13 in the Veneto Region. We studied the data
      concerning the admissions in the ER of this area, especially those involving
      migrants. We tested the hypotheses that the traffic injuries were associated with
      the summer tourism flow. Our results say that, on the contrary, it may be
      associated with the presence of migrant workers in the local industrial system.

PMID- 16454415
TI  - [Epidemiology in Italy: past and future].

PMID- 16454416
TI  - [The impact of Israeli occupation on Palestinians' health].

PMID- 16454418
TI  - [Industrial system and health hazards: significant issues concerning occupational
      health. Relevance and reliability of epidemiological research].

PMID- 16454417
TI  - [Consulting an ethics committee, when is it necessary? Two examples].
AB  - We described the indications of laws and the commitment of researchers on the
      decision to submit two projects regarding observational studies to the ethics
      committee. Out of the two studies, the first one shows problems on data
      confidentiality and privacy, while the other one entails a risk, even though
      minimum, of physical damage for the study subjects. In Italy, the laws foreseeing
      the submission of research projects to the ethical committee are the Code for
      Personal Data Protection (Dlgs 196/2003), and the Good Clinical Practice
      regulations for the protection of research subjects (DM 15 luglio 1997); other
      provisions tied to such basic laws are also mentioned in the article. The laws on
      the protection of personal data tend to simplify prescriptions when the research
      relates to public health issues; the laws on the protection of the research
      subject do not almost totally pertain observational studies. We concluded that
      the researchers are free to submit or not both projects to the ethics committee.
      We underlined that the sensitivity of researchers on the endorsement of the same
      ethical principles can be different. We would think convenient also for
      epidemiological research, as well for clinic research, to establish an uniform
      approach. The recent issuing of the Additional Protocol on biomedical research to
      the Oviedo Convention may provide an opportunity.

PMID- 16454420
TI  - A heart for the military.
AB  - On September 20 of this year, MDA Executive Director Dick Diercks traveled to
      Camp Ripley at the invitation of the Minnesota National Guard to observe the
      dental screening process being provided to troops about to be deployed overseas.
      The following report is based on Mr. Diercks' tour of the camp with Major (Dr.)
      Kristin Rajala of the MDA Saint Paul District Dental Society.

PMID- 16454419
TI  - Handled with care.

PMID- 16454421
TI  - What to do when the doctor dies. Part two.

PMID- 16454422
TI  - "Keeping the life in your life's work": a summary report on the ADA's National
      Institute on Dentist Well-Being.

PMID- 16454423
TI  - When the walls come tumbling down: a pathway to addiction.

PMID- 16454424
TI  - Dental hygienists' interest in community collaborative practice: results of a
      survey.

PMID- 16454425
TI  - Street of Reality's tour of the north.

PMID- 16454426
TI  - What's a dentist to do? "Just" dentistry.

PMID- 16454427
TI  - Something they can keep.

PMID- 16454428
TI  - Physician leadership and the common good.

PMID- 16454429
TI  - Defining the market value of a physician.

PMID- 16454430
TI  - Wyeth responds to criticism.

PMID- 16454431
TI  - Fault lines.

PMID- 16454432
TI  - A practical office-based perspective on patient safety.

PMID- 16454433
TI  - Patient safety and the art and science of medicine.

PMID- 16454434
TI  - Changing systems the hands-on way. The VA National Center for Patient Safety's
      Museum.

PMID- 16454435
TI  - Electronic medical records.

PMID- 16454436
TI  - Electronic prescribing at Johns Hopkins Community Physicians: a success story.

PMID- 16454437
TI  - Operation Lifeline: health care professionals from Maryland respond to Hurricane
      Katrina.

PMID- 16454438
TI  - Cord-blood procedures raise legal risks for doctors and hospitals.

PMID- 16454439
TI  - Elemental etymology.

PMID- 16454440
TI  - Provider adoption of health information technology.

PMID- 16454441
TI  - [Erythrocyte fluidity in patients with hyperlipidemia during statins therapy].
AB  - The lipid composition of erythrocyte membrane is in a state of dynamic
      equilibrium with plasma lipoproteins and reflects the processes taking place in
      extracellular environment. The recent studies were devoted to the phenomenon of
      modification of atherosclerosis development by statins. The aim of the study was
      evaluation of three statins: simvastatin, atorvastatin and pravastatin on plasma
      lipidogram and fluidity of erythrocytes membranes in patients (pts) with
      hyperlipidemia (hlp) type II. INVESTIGATED GROUP: the study comprised 114 pts,
      including 94 pts with hlp type II without concomitant chronic diseases and 20
      healthy volunteers. Pts were qualified to treatment with statins if their LDL
      cholesterol concentration (LDL-C) was above 170 mg/dL (4,1 mmol/L), total
      cholesterol (TC) > 250 mg/dL (6,5 mmol/L) and triglicerydes (TG) < 400 mg/dL (4,5
      mmol/L). Pts were randomised to three groups: group I-n = 31 pts treated with
      atorvastatin (10 mg/d); group Il-n = 31 with simvastatin (20 mg/d), group III-n =
      32 with pravastatin (20 mg/d). METHODS: after 4 and 12 weeks of active treatment
      the following parameters were determined: TC, HDL-C, TG (by enzymatic method
      using BioMerieux tests); LDL-C was calculated from the Friedewald formula and
      erythrocyte membranes fluidity by electron paramagnetic resonance with two spin
      labels (5-DSA, 16-DSA). RESULTS: During statin therapy significant decrease of
      TC, LDL-C, TG was observed, both after 4 and 12 weeks, as compared with initial
      values. All statins after 4 weeks of therapy caused a significant increase of
      membrane fluidity in its surface layer at carbon 5 depth. The values of parameter
      S after 12 weeks did not differ significantly from the values in the control
      group. The percent decrease of membrane microviscosity at carbon 5 depth did not
      correlate significantly with percent changes plasma TC and LDL-C. Atorvastatin
      appeared to be the strongest drug liquidizing erythrocytes membranes. There were
      no significant changes in fluidity of membrane in its deeper layers (at carbon 16
      level). CONCLUSION: Statins therapy was beneficial not only for modification of
      plasma lipids but caused the increase of erythrocytes membrane fluidity in the
      surface layer.

PMID- 16454442
TI  - [Morphology of neutrophils in centarians].
AB  - Recently, centenarians are involved in many research programs as they are
      believed to represent so-called successful aging. The aim of the study was to
      characterize morphological alterations observed in neutrophils from their
      peripheral blood. The study involved 40 centenarians (group B--34 females and 6
      males) as well as 40 young healthy subjects aged 20-30 years (group K--35 females
      and 5 males). The study is a part of the Polish Centanarians Program coordinated
      by the International Institute of Molecular and Cell Biology in Warsaw. In this
      study, the morphometry of neutrophils from blood smear was performed in all
      studied subjects. Additionally, in centenarians, the relationship between
      observed alteration and serum level of vitamin B12 and folic acid was analyzed.
      Both the mean size of granulocytes and the mean value of neutrophil lobe counts
      were higher in group B vs group K (15.5 +/- 0.6 mm and 13.9 +/- 0.7 mm; p<0.0001
      and 4.01 +/- 0.7 and 3.2 +/- 0.2; p<0.0001). Chromatin chips and toxic granules
      in cytoplasm were observed more often in centenarians as well (39/40 vs 20/40-
      p<0.0001 and 40/40 vs. 23/40--p<0.0001; respectively). In centenarians, there was
      no relationship between the presence of morphological alterations in granulocytes
      and the serum level of vitamin B12 and folic acid. In conclusion, morphological
      alterations were very common in studied centenarians. Detailed analysis of
      biochemical parameters and clinical status is necessary to answer the question
      about their pathomechanism.

PMID- 16454443
TI  - [Serum leptin concentration and sympathetic activation estimated on the
      adrenaline and noradrenaline serum concentration in patients with obstructive
      sleep apnea].
AB  - Hypertension, coronary heart diseases, obesity, diabetes mellitus are often
      present in patients with obstructive sleep apnea (OSA). The aim of the study was
      to estimate the serum leptin concentration and sympathetic activity in patients
      with obstructive sleep apnea and in control group. INVESTIGATED GROUP: 51 persons
      (F6, M45) were included into the study. The control group (GK) consisted of 15
      snoring person (15 M) in the age x = 44.19 +/- 14.60, study group (GB) consisted
      of 36 patients with OSA (6F, 30M) in the age 5 1.47 +/- 8.95 years. METHODS:
      Leptin was measured by RIA methods using the HUMAN LEPTIN RIA KIT (LINCO
      Research, Inc).: adrenaline and noradrenaline were measured in the serum by HPLC
      methods (BIO-RAD). RESULTS: The serum concentrations of leptin (ng/mL),
      adrenaline and noradrenaline (pg/mL) in patients with OSA compared with control
      group were respectively 15.55 +/- 11.26 : 61.2 +/- 27.4: 523.2 +/- 165.1 vs
      10.34+/- 6.86 : 47.7 +/- 27.3: 447.9 +/- 102.6. There was positive significant
      correlation between leptin concentration and BMI (r = 0,34) and serum leptin and
      adrenalin concentration (r = 0,34). The serum leptin concentration was
      significantly higher in the female group. In the male group there was tendency to
      increase leptin concentration together with degree of OSA grade estimated by AHI
      and AHI <50 leptin concentration 12.23+/- 6.96 ng/mL vs AHI>50 and leptin
      concentration 13.35 +/- 3.54ng/ml. CONCLUSIONS: 1. In the group of patients with
      OSA the serum concentrations of leptin, adrenaline and noradrenaline were higher
      then in control group. 2. There are positive statistical significant correlation
      between serum leptin levels and BMI and serum adrenaline concentration in the
      study group. 3. The serum leptin concentration was higher in the female group. 4.
      There was tendency to increased leptin concentration in the study group together
      with degree of OSA grade estimated by AHI. 5. Our results confirm correlation
      between leptin and sympathetic activity and their influences on obesity and
      degree of OSA grade in studied group.

PMID- 16454444
TI  - [Assessment of antineutrophil-cytoplasmic autoantibodies (ANCA) in type 1
      diabetic patients].
AB  - Polymorphonuclear neutrophils and inflammatory process play a key role in the
      development of late diabetic vascular complications. Antineutrophil-cytoplasmic
      autoantibodies (ANCA) are considered important serological markers for
      vasculitis. The aim of study was the assessment of prevalence ANCA in type 1
      diabetic patients and evaluation of the relationship between ANCA and diabetic
      microangiopathy. 94 type 1 diabetic subjects, 47 male and 47 female, aged 30.7 +/
      9.6 years, with mean duration of diabetes 9.5 +/- 6.8 years and HbA1c 7.9 +/-
      1.3% were included to this study. ANCA were detected by the indirect
      immunofluorescence test and the specificity was evaluated by ELISA test. The
      significantly positive result of ANCA was noticed in 11 subjects (12%), anti
      myeloperoxidase (anti-MPO) in 9 and anti-proteinase 3 (anti-Pr-3c) in 2 subjects.
      It was not observed any differences in sex, parameters of metabolic control,
      duration of diabetes, C-reactive protein levels and diabetic retinopathy and
      nephropathy between group with ANCA and without ANCA (p>0.05). Moreover, we did
      not notice relationship between ANCA and the risk of late diabetic complications
      (retinopathy: OR 1.64; 95% CI 0.46-5.82, p = 0.52 and nephropathy: OR 0.16; 95%
      CI 0.02-1.35, p = 0.10). The obtained results do not fully confirm hypothesis
      that ANCA are connected with the development of diabetic microangiopathy.

PMID- 16454445
TI  - [Arterial hypertension--what does the patient know?].
AB  - The purpose of this study was to analyse knowledge concerning arterial
      hypertension in patients with treated arterial hypertension. The inquiry was
      performed in 100 patients (50 women, 50 men) aged of 25-75 years. The average age
      of woman was 53 years, the man--55 years. In the survey majority of them were
      city dwellers (83%). Minority of respondents 4-46% realized that arterial
      hypertension can be associated with heart diseases, arteriosclerosis, kidneys
      diseases, diabetes, obesity and other diseases. Almost 58% took medicine
      systematically, 51% applied changes in the diet, 19% introduced exercise reducing
      body mass, 41% of patients always possessed money to by medicine. Despite
      presence of hypertension a lot of respondents drank alcohol 68% men, 50% women,
      smoked a cigarettes 28%. CONCLUSIONS: The reason of the inadequate motivation for
      treatment of arterial hypertension was the lack of general knowledge about
      hypertension.

PMID- 16454446
TI  - [The orthopaedic status of a selected severe haemophilia group].
AB  - The aim of the present study was to describe the orthopaedic status of patients
      with severe haemophilia, and to relate this status to the type of replacement
      therapy received by patients prior to the study. Ninety two haemophiliacs with
      median age 26 were included. Six joints--knees, elbows and ankles were evaluated
      clinically using the Gilbert scale. The evaluation included physical status (0-12
      points/joint) and pain score (0-3 points/joint). X-ray examinations were
      evaluated according to the Pettersson scale (0-13 points/joint). On all scales,
      normality was represented by 0 score. Knees were the most affected joints. Eighty
      four patients (91.3%) reported pain. Only one patient scored 0 on the Gilbert
      scale, and another on the Pettersson scale. Thirty seven percent of patients used
      orthopaedic equipment occasionally or constantly. Twenty five percent of patients
      had a history of orthopaedic surgery. Thirty eight percent were unemployed and
      received some form of social subvention. On demand treatment was applied. None of
      the patients received primary prophylaxis. The mean consuption of clotting factor
      concentrates was 68,054 IU per patient during the 12 months period prior to the
      current study. The results of this study indicate that vast majority of severe
      haemophilia patients in Poland above 20 are affected by haemophilic arthropathy.
      This disabling complication of severe haemophilia can be prevented only by
      introducing primary prophylaxis from the first years of life.

PMID- 16454447
TI  - [Primary lymphoma of the thyroid--diagnostic and treatment problems. The case
      report].
AB  - The authors present the case of primary malignant thyroid lymphoma and problems
      with distinguishing between Hashimoto's thyroiditis and primary thyroid lymphoma.
      Primary malignant thyroid lymphoma (PMTL) is a rare disease and difficult to
      diagnose. The appearance of PMTL may be preceded by Hashimoto's thyroiditis. The
      biopsy is useful but often only surgical treatment allows to establish diagnosis.
      The treatment of PMTL includes surgical treatment, chemo- and radiotherapy. The
      prognosis depends on the disease period.

PMID- 16454448
TI  - [The influence of body mass reduction on metabolic disorders and complications in
      patient with morbid obesity. Three years observation].
AB  - We describe a case of 40-year-old male with giant obesity, with signs of
      metabolic syndrome, treated with low-calorie diet (700 kcal in 1-st year of
      treatment, 1200 kcal in 2-nd and 3-rd year of treatment), and supplementary
      pharmacotherapy with sibutramine. Patient initial weight was 170,9 kg, height 189
      cm, BMI = 47,8 kg/m2. In summary weight loss in this patient was 52,9 kg, this is
      30,9% of initial value. This case report shows that giant obesity with
      accompanying metabolic disorders and complications can be treated with
      combination of diet, physical activity and pharmacotherapy. The key factor of
      successful therapy is personal motivation of a patient.

PMID- 16454449
TI  - [Behcet's disease--difficulty in diagnostic and management].
AB  - We present a 31-year-old female patient with Behcet's disease. Behcet's disease
      is a systematic vasculitis of unknown cause involving veins and arteries of all
      sizes and having reccurent mucocutaneous and frequent ocular involvement. Our
      patient was suffering from oral and genital ulcers, fever, painful left knee and
      erythema nodosum. After having excluded differential diagnoses Behcet's disease
      was diagnosed. The treatment must be individual and it depends on the presence
      and severity of symptoms. The optimal improvement was observed after treatment
      with azathioprine, cyclosporine A and metylprednisolon. Behcet's disease is very
      seldom in our country but perhaps sometimes it isn't good diagnosed.

PMID- 16454450
TI  - [Tumour markers of pancreatic cancer (tumour associated antigens)].

PMID- 16454451
TI  - [Aging and endocrine glands].

PMID- 16454452
TI  - [The role of PDGF in pathogenesis of selected disorders].

PMID- 16454453
TI  - [Drugs selectively blocking proinflammatory cytokines and cell receptors].

PMID- 16454454
TI  - [Buerger's disease in women].

PMID- 16454455
TI  - [Recent discoveries of the early history of insulin production in Poland].

PMID- 16454456
TI  - [Undifferenciated vasculitis].

PMID- 16454457
TI  - Corporate manslaughter.
AB  - The Government published its long-awaited draft Bill on the creation of a new
      criminal offence of corporate manslaughter shortly before the May 2005 general
      election. The Bill was included in the Queen's Speech after the general election
      and, with a Labour government back in power, the new offence could be on to the
      statute book as early as 2006. The Home Affairs Committee and the Work and
      Pensions Committee announced ajoint inquiry to consider and report on the Bill.
      This is expected to be completed by the end of 2005. Pressure for reform of the
      law relating to manslaughter and corporate killing arose out of a series of high
      profile fatal accidents, including several rail crashes. There has been said to
      be an increasing concern amongst the public that companies and organisations are
      not being held sufficiently accountable for deaths caused by their criminal
      negligence. The author acted in the first of the major cases, representing the
      directors accused of manslaughter following the Herald of Free Enterprise capsize
      disaster in 1987.

PMID- 16454458
TI  - Prosecuting psychiatric inpatients--where is the thin blue line?
AB  - Violence by psychiatric inpatients is under-reported and the involvement of the
      police is limited. No research has specifically investigated the views of the
      police force in this area. Ten senior police officers were interviewed using a
      semi-structured format to elucidate their views. A thematic analysis of the
      results highlighted training needs, and concerns around the public interest and
      evidential tests where the mentally ill are concerned. However, there was also a
      clear willingness to attend incidents and support the individuals involved.
      Possible sources of bias are considered. Issues of policy for psychiatric
      hospitals are noted as are victim-related factors.

PMID- 16454459
TI  - Homicide in the Canadian Prairies: spousal killers and recidivism.
AB  - This prospective study identifies the rate of recidivism in spousal homicide
      offenders after release from their sentences for homicide and explores factors
      associated with re-offending. A non-selective sample of 131 released spousal
      killers was studied, using the CPIC (Canadian Police Information Centre) to
      access post-release criminal convictions. The mean follow-up period was ten
      years, and ranged from eight months to 37 years. Fifty-one offenders (38.9%) re
      offended. Violent crimes were committed by 27 (20.6%) offenders. Several factors
      were associated with recidivism but older age at release was the most
      significant. Violent recidivism in released spousal killers occurred at the rate
      of 21%. Ageing was a mitigating factor and should be considered in forensic
      assessments and given more weight in parole decisions involving any release.

PMID- 16454460
TI  - Suicides in Trakya region, Turkey, from 1984 to 2004.
AB  - The aim of this study is to investigate some features of suicide cases in Trakya
      region, Turkey. During the 21-year period from January 1984 to September 2004,
      there were 137 suicide cases autopsied by the Department of Forensic Medicine,
      Trakya University. Suicides comprised 16.1% of all forensic autopsies. Twenty
      seven per cent of the cases were aged between 21 and 30 years and the mean age
      was 39.7 years. Males constituted 78.1% of the cases. The most frequent method of
      suicide was hanging (40.1%), followed by firearms, and poisoning. Overall,
      suicide rates in males showed an increase in the last five years. Most of the
      suicides occurred in the winter months. In conclusion, since suicides present a
      major public health problem, detection and prevention methods must be developed
      for high-risk groups.

PMID- 16454461
TI  - Possible predictors of outcome for conditionally discharged patients--a
      preliminary study.
AB  - Conditional discharge for restricted hospital order patients is by and large a
      successful process. The present study aimed to identify variables among a cohort
      of conditionally discharged patients in the West Midlands that would predict
      whether an individual was more likely to be readmitted to hospital, involved in a
      serious incident, to be recalled to hospital or given an absolute discharge. A
      retrospective case note analysis was undertaken. Logistic regression analysis was
      used to identify variables that could predict outcome. Patients were six times
      more likely to be readmitted to hospital if they misused drugs and nine times
      more likely if they self-harmed. They were also six and four times more likely to
      be involved in a serious incident if they misused alcohol and drugs respectively.
      Patients were five times more likely to be recalled to hospital if they did not
      have close social support and were four and a half times more likely to get an
      absolute discharge if they lived in supported accommodation. Conditional
      discharge is an effective model of community care for restricted hospital order
      patients. Addressing the problems caused by drug and alcohol misuse, self-harming
      behaviour, recognising the importance of a close social support network and
      developing more appropriate housing for these individuals will help make the
      process more successful.

PMID- 16454462
TI  - Amphetamines as potential inducers of fatalities: a review in the district of
      Ghent from 1976-2004.
AB  - Abuse of amphetamine (AMP) and its derivatives, such as 3,4
      methylenedioxymethamphetamine (MDMA, 'Ecstasy'), 3,4
      methylenedioxyethylamphetamine (MDEA, MDE), and 3,4-methylenedioxyamphetamine
      (MDA) is an important public issue. Fatalities following ingestion of these
      substances are not infrequent in current forensic practice. The aim of this study
      was twofold. Firstly, considering the wide range of blood levels reported in
      fatalities, to provide insight into the interpretation of a quantified blood
      level and, secondly, to examine and discuss possible causes, mechanisms and
      manners of death. All the medico-legal files between January 1976 and December
      2004 were skimmed through to investigate whether amphetamine and/or derivatives
      were involved in the fatal outcome. Particularly, in addition to overdose cases
      due to or including amphetamines, all amphetamines-related fatalities were
      examined. In addition to AMP, MDMA, MDEA, and MDA, two other amphetamine
      derivatives, namely 4-methylthioamphetamine (4-MTA) and para-methoxyamphetamine
      (PMA) were considered. In 34 fatalities, amphetamines were involved and the
      majority were men, under the age of 25 years. A wide range of blood levels was
      found: e.g. MDMA blood concentrations in cases of 'pure' intoxication were found
      between 0.27 and 13.51 microg/ml. The age and sex distribution as well as the
      broad range of quantified amphetamines blood levels were in line with those
      reported in the literature. In our study group, 'pure' intoxications with
      amphetamines, polydrug overdoses, and the combination of amphetamines use and
      polytrauma were the most prominent causes of death. Considering the manner of
      death in these fatalities, unintentional overdoses were most frequent, though
      suicides, traffic accidents, and criminal offences associated with amphetamines
      use also accounted for significant percentages. Acute to subacute cardiopulmonary
      failure was the most frequent mechanism of death, followed by (poly)trauma,
      mechanical asphyxia, and hyperthermia, respectively. In conclusion, although
      amphetamines-related fatalities are only a fraction of the total number of
      fatalities studied at our Department, their contribution to current forensic
      practice has been increasing during the last few years. As there is still
      considerable debate as to what level of amphetamines can be toxic or even
      potentially lethal, it is strongly advisable to interpret the anatomo
      pathological findings and the toxicological results together in arriving at a
      conclusion. This guideline is important in view of the different possible
      mechanisms of death which implicate quite different survival times following
      intake of amphetamine and/or its derivatives (e.g. cardiopulmonary complications,
      hyperthermia).

PMID- 16454463
TI  - Assessing decision-making capacity: a survey of psychiatrists' knowledge.
AB  - We aimed to survey the knowledge of psychiatrists on the assessment of decision
      making capacity. Ninety-two psychiatrists of all grades and three other doctors
      attending a regional conference were marked on their verbal response to the
      question 'What are the key elements in the assessment of a patient's capacity?'
      On average, participants mentioned three out of the five elements in testing
      decision-making capacity. Scores were negatively correlated with age (Pearson's
      coefficient 0.275, sig 0.007). Section 12 status and grade had no impact on
      knowledge. Most psychiatrists of all grades have a reasonable knowledge of
      assessing decision-making capacity. Over a third of participants mentioned two or
      fewer of the five points, suggesting inadequate knowledge. Assessing decision
      making capacity needs to be emphasised in training throughout psychiatrists'
      careers--not just at the start.

PMID- 16454464
TI  - Firearms accidents in Northern India (1980-2000).
AB  - This paper investigates firearms accidents from the last two decades (1980-2000),
      with information received from the three North Indian states, Chandigarh, Delhi
      and Himachal Pradesh and from the military and paramilitary organisations working
      in the region. In this study 139 cases were analysed for evaluation of various
      parameters such as type of accident, type of firearm used, age, sex, occupation
      and caste of victim, day of the week and the season in which the accident
      occurred, place of incident and location of wound. Information was extracted from
      the case histories and First Information Reports (FIR), and also from autopsy and
      injury reports. The accidents were self-inflicted in nine cases while another
      person fired the weapon in 130 cases. Most accidents occurred during hunting or
      from mishandling the firearm. Gun cleaning accidents rarely occurred and few
      cases were due to technical defects of the firearm. Shotguns and rifles caused
      most of the accidents. Shotgun accidents occurred mostly in rural areas whereas
      the cases involving rifles and handguns were from urban areas. Victims were
      predominantly male with a mean age of 26 and 30 years for males and females
      respectively. Victims' occupations were principally agricultural followed by
      service class and housewives. The most aggressive community was the Kshatriya
      caste. Most of the accidents occurred during the winter season and on days
      between Sunday and Tuesday. Accident locations were most commonly the forest, the
      fields or the home. The chest and head were the most common anatomical sites of
      injury. All accidental cases were the result of only one firing. It is important
      to mention that, based on these findings, firearm accidents could be reduced
      significantly if firearm holders were better trained regarding the handling and
      safety aspects of their guns, particularly farmers to whom firearm licences are
      granted specifically for the protection of crops.

PMID- 16454465
TI  - The clinical duty of care: is it enough that the doctor did what all or many of
      the other doctors do?
AB  - Who decides what is required in order to fulfil the duty of care, the doctors or
      the judges? This paper examines what the judges have been saying of late and
      gives an analysis of recent judgements. It also looks at the extent to which
      judges are challenging the medical experts. The trend away from medical
      paternalism to patient autonomy is discussed in the light of continuing
      uncertainty of the law and medical practice.

PMID- 16454467
TI  - The applicability of DNA techniques in investigations of hospital malpractices: a
      case report.
AB  - DNA analysis has been used successfully in a number of parentage cases and for
      the purposes of identification. However DNA typing is still not generally
      integrated efficiently into hospital systems in India. I report here the use of
      DNA evidence in a parentage dispute that arose as a result of a bizarre sequence
      of events in a maternity ward of General Hospital, Chandigarh, India. The
      changing standards of hospital practice and social attitudes such as gender bias
      are likely to augment medico-legal problems in India. There is good reason for
      DNA profiling methods to be introduced into the hospitals.

PMID- 16454466
TI  - Diabetic ketoacidosis--a possible complicating factor in deaths associated with
      drug overdose: two case reports.
AB  - Two cases are described where diabetic ketoacidosis was found in conjunction with
      significant levels of prescription drugs. Case 1: A 45-year-old woman with a
      history of insulin-dependent diabetes mellitus was found to have Armanni-Ebstein
      nephropathy characteristic of hyperglycaemia with a vitreous humour glucose level
      of 63.1 mmol/L and a beta-hydroxybutyrate level of 14.25 mmol/L. Ancillary
      toxicological evaluation revealed a lethal level of sertraline (2.5 mg/L), with
      an elevated level of methadone (0.23mg/L). Death was due to diabetic ketoacidosis
      complicating mixed drug toxicity. Case 2: A 27-year-old man with a history of
      insulin-dependent diabetes mellitus was found to have Armanni-Ebstein nephropathy
      with a vitreous humour glucose level of 51.7 mmol/L and a beta-hydroxybutyrate
      level of 18.6mmol/L. Ancillary toxicological evaluation revealed a potentially
      lethal level of methadone of 0.39mg/L. Death was attributed to diabetic
      ketoacidosis complicating methadone toxicity. These cases demonstrate a situation
      where drug toxicity led to diabetic ketoacidosis resulting in death most likely
      from a combination of factors. Measuring vitreous humour glucose and beta
      hydroxybutyrate levels is important in individuals with histories, or scene
      evidence, of insulin-dependent diabetes mellitus, in addition to toxicological
      screening when there is evidence of possible drug taking. It appears that drug
      intoxication in both cases had impaired the ability to administer insulin,
      resulting in the development over time of diabetic ketoacidotic states. Lethal
      mechanisms were, therefore, more complex than simple drug toxicity or diabetic
      ketoacidosis in isolation.

PMID- 16454468
TI  - Uneventful recovery from suicidal hanging: a case report.
AB  - Although hanging accounts for a considerable number of suicidal deaths in Sri
      Lanka, on rare occasions the victims survive. A few cases have been reported in
      the literature where victims survived after varying periods of unconsciousness.
      It has been observed that death does not necessarily result from hanging,
      provided the victim is brought down promptly and resuscitated actively and
      vigorously. This paper focuses on an unusual case of a 39-year-old male who
      survived after resuscitation, without any adverse neurological outcome, after a
      suicide attempt by hanging.

PMID- 16454470
TI  - Anthocyanins in berries of Maqui (Aristotelia chilensis (Mol.) Stuntz).
AB  - The anthocyanin composition of berries of Maqui [Aristotelia chilensis (Mol.)
      Stuntz] was determined by HPLC with photodiode array and MS detection. Eight
      pigments corresponding to the 3-glucosides, 3,5-diglucosides, 3-sambubiosides and
      3-sambubioside-5-glucosides of delphinidin and cyanidin were identified, the
      principal anthocyanin being delphinidin 3-sambubioside-5-glucoside (34% of total
      anthocyanins). The average total anthocyanin content was 137.6 +/- 0.4mg/100g of
      fresh fruit (211.9 +/- 0.6 mg/100g of dry fruit). The relative high anthocyanin
      content and the important presence of polar polyglycosylated derivatives makes
      the fruits of A. chilensis an interesting source of anthocyanin extracts for food
      and pharmaceutical uses.

PMID- 16454469
TI  - High anti-inflammatory activity of harpagoside-enriched extracts obtained from
      solvent-modified super- and subcritical carbon dioxide extractions of the roots
      of Harpagophytum procumbens.
AB  - Solvent-modified carbon dioxide extractions of the roots of Harpagophytum
      procumbens have been investigated with respect to extraction efficiency and
      content of harpagoside, and compared with a conventional extract. The effects of
      pressure, temperature, type and concentration of the modifier have been examined.
      Two extraction steps were necessary in order to achievehigh anti-inflammatory
      harpagoside-enriched extracts. The first extraction step was carried out in the
      supercritical state using carbon dioxide modified with n-propanol to remove
      undesired lipophilic substances. The main extraction was performed either in the
      supercritical or in the subcritical state with carbon dioxide modified with
      ethanol. The supercritical fluid extraction resulted in extracts containing up to
      30% harpagoside. The subcritical extracts showed a harpagoside content of ca.
      20%, but the extraction yield was nearly three times greater compared with
      supercritical conditions. The total harpagoside recovery resulting from the sum
      of the extract and the crude drug residue was greater than 99% in all
      experiments. The conventional extract and two carbon dioxide extracts were tested
      for in-vitro inhibition of 5-lipoxygenase or cyclooxygenase-2 biosynthesis. Both
      carbon dioxide extracts showed total inhibition on 5-lipoxygenase biosynthesis at
      a concentration of 51.8 mg/L. In contrast, the conventional extract failed to
      show any inhibition of 5-lipoxygenase biosynthesis.

PMID- 16454471
TI  - A rapid TLC autographic method for the detection of xanthine oxidase inhibitors
      and superoxide scavengers.
AB  - A new bioautographic assay suitable for the localization of xanthine oxidase
      inhibitors and superoxide radical scavengers present in a complex matrix is
      described. Enzyme activity is detected by reaction of superoxide radicals with
      nitroblue tetrazolium to form a blue formazan salt. Both activities can be
      differentiated using a non-enzymatic version of the autographic assay wherein
      superoxide is chemically generated.

PMID- 16454472
TI  - Structural studies of zoospore attractants from Trachelospermum jasminoides var.
      pubescens: taxifolin 3-O-glycosides.
AB  - (2S, 3S)-Taxifolin 3-O-arabinoside, a new dihydroflavonol glycoside, together
      with the known substances, (2R 3R)-taxifolin 3-O-arabinoside, astragalin,
      isoquercitrin, and cosmosiin, were isolated from the leaves of Trachelospermum
      jasminoides var. pubescens. Structural elucidation was carried out by
      spectroscopic methods, and the absolute configurations of C-2 and C-3 in
      taxifolin 3-O-arabinosides were determined on the basis of circular dichroism.
      Unlike the dihydroflavonol glycosides, (2R 3R)-taxifolin 3-O-glucoside and (2R,
      3R-taxifolin 3-O-arabinoside, the novel (2S, 3S)-taxifolin 3-O-arabinoside is not
      effective as a zoospore attractant of the plant pathogenic fungus Aphanomyces
      cochlioides.

PMID- 16454473
TI  - Simultaneous HPLC analysis, with isocratic elution, of glycyrrhizin and
      glycyrrhetic acid in liquorice roots and confectionery products.
AB  - Glycyrrhizin (1), the main active principle of Glycyrrhiza glabra (liquorice)
      roots, is extensively used in herbal medicines, in pharmaceutical preparations
      and confectionery products. A feasible and reliable method which allows the
      simultaneous analysis of 1 and its aglycone, 18beta-glycyrrhetic acid (2), by
      means of an isocratic HPLC procedure is described. The system uses a C8 column as
      the stationary phase, and a mixture of acetonitrile, methanol, water and glacial
      acetic acid as the mobile phase. Good linearity was found in the concentration
      ranges 1-50 and 0.05-2.50 microg/mL for 1 and 2, respectively. A simple and rapid
      sample pre-treatment, based on the extraction of the two analytes with a mixture
      of water and ethanol, was developed for the examination of liquorice
      confectionery products and root samples. The HPLC method was shown to be
      appropriate, in terms of precision and feasibility, for the quality control of
      the analytes in these matrices.

PMID- 16454474
TI  - Labdane diterpenes from Juniperus communis L. berries.
AB  - A phytochemical study of the methanol extract of Juniperus communis berries was
      undertaken. The crude extract was analysed by HPLC-UV and the isolation of the
      minor compounds was performed by centrifugal partition chromatography. By this
      means, five diterpenes were isolated, one of which was a new labdane diterpene
      15,16-epoxy-12-hydroxy-8(17),13(16),14-labdatrien-19-oic acid. The structures of
      the isolated compounds were elucidated by spectroscopic methods, including UV,
      NMR, MS and HR-MS.

PMID- 16454475
TI  - Chemical constituents of rice (Oryza sativa) hulls and their herbicidal activity
      against duckweed (Lemna paucicostata Hegelm 381).
AB  - Four new compounds, stigmastanol-3beta-p-glyceroxydihydrocoumaroate (1),
      stigmastanol-3beta-p-butanoxydihydrocoumaroate (2), lanast-7,9(11)-dien
      3alpha,15alpha-diol-3alpha-D-glucofuranoside (3) and 1-phenyl-2-hydroxy-3,7
      dimethyl-11-aldehydic-tetradecane-2-beta-D-glucopyranoside (4), along with
      several known compounds were isolated from the methanol extract of hulls of Oryza
      sativa. The new structures were established by one- and two-dimensional NMR and
      in combination with IR, EI/MS, FAB/MS and HR-FAB/ MS. Compound (3) strongly
      inhibited the growth of duckweed (Lemna paucicostata Hegelm 381), whilst
      compounds (2) and (4) exhibited weak inhibition.

PMID- 16454476
TI  - Identification and differentiation of Panax species using ELISA, RAPD and eastern
      blotting.
AB  - Immunochemical and genetic methods have been developed in order to distinguish
      Panax spp. With the aim of establishing immunochemical methods, two hybridomas
      (3H4 and 5H8), each secreting a monoclonal antibody (MAb) against proteins of
      Panax ginseng, were prepared by fusing splenocytes immunized with two kinds of
      ginseng water-soluble fractions and a hypoxanthine-thymidine-aminopterin
      sensitive mouse myeloma cell line, P3-X63-Ag8-U1. MAb 3H4 cross-reacted with four
      Panax spp., whereas the MAb 5H8 cross-reacted with P. ginseng in the enzyme
      linked immunosorbent assay (ELISA). ELISA and western blotting methods using a
      ginseng water-soluble fraction as the solid-phase antigen were developed for the
      unambiguous authentication of P. ginseng. A combination of random amplified
      polymorphic DNA (RAPD) and eastern blotting analyses using anti-ginsenoside Rb1
      and Rgl monoclonal antibodies was used for the identification of P. notoginseng,
      P. quinquefolius and P. japonicus. RAPD can be used to differentiate the species
      of Panax from each other. An important parameter used for differentiating P.
      notoginseng is the absence of ginsenoside Rc in the extract of P. notoginseng
      with eastern blotting. The combination of these methods enabled a reliable
      identification of Panax spp.

PMID- 16454477
TI  - Quantitative analysis of flavonol glycosides in Ginkgo biloba: a comparison of
      two analytical methods.
AB  - A comparison of testing methods for constituents of Ginkgo biloba was performed
      as part of the process for determining which of the many available analytical
      methods was most appropriate for inclusion in the American Herbal Pharmacopoeia
      (AHP). Three primary methods were reviewed: those adopted by the European
      Pharmacopoeia, the National Science Foundation-Institute for Nutraceutical
      Advancement (NSF-INA) and the United States Pharmacopeia. Methods were compared
      by evaluating sample preparation and hydrolysis, precision and methods of total
      flavonol glycoside calculation by two independent laboratories. The AHP adopted
      the method of NSF-INA for inclusion in the AHP monograph owing to observed
      superiority of this method in terms of precision, glycoside calculation, ease of
      sample preparation and chromatographic parameters.

PMID- 16454478
TI  - Current awareness in phytochemical analysis.

PMID- 16454479
TI  - [Criteria for classification of upper limb work-related musculo-skeletal
      disorders due to biomechanical overload in occupational health. Consensus
      document by an Italian Working Group].
AB  - BACKGROUND AND OBJECTIVE: In a preliminary consensus document the authors
      proposed criteria and methods to identify upper limb work-related MSDs due to
      biomechanical overload. With this document they intend to define severity
      according to shared models and procedures so as to fit behaviours to diagnostic
      procedures and their medical-legal assessment. This becomes especially important
      in view of Ministerial Decree of April 27 2004 fixing the new lists of diseases
      having a possible work-related origin that must be reported by law in accordance
      with art. 139 of law n. 1124, and also on account of the impact of such diseases
      which, for the first time in Italy, are regulated by law. CONTENTS: The working
      group, which included INAIL and ISPESL experts and was fully supported by SIMFER
      (Italian Society of Physical Medicine and Rehabilitation) and SINC (Italian
      Society of Clinical Neurophysiology), defined a general clinical procedure
      (anamnesis, objective examination and instrumental assessment) regarding each
      portion of the concerned upper limb (shoulder, elbow and wrist/hand). Once the
      presence and characteristics of anatomic and functional damages are established,
      the results allow a classification scheme to be proposed of upper limb diseases
      (tendon disorders and entrapment neuropathy) divided into 6 increasing severity
      stages: initial, medium, medium-severe, severe and extremely severe. Special
      attention was paid to two instrumental examinations that proved to be of great
      clinical interest, at least in occupational health: echography of soft tissues
      (in appendix) and electroneurography for entrapment neuropathy. The limitations
      of this proposal are discussed but the main goal was achieved: to standardize
      terms and provide homogeneous criteria to achieve classification of upper limb
      damage due to biomechanical overload for increasing severity levels. The working
      group research activity is part of a research project funded by ISPESL.

PMID- 16454480
TI  - Effects of retirement and grandchild care on depressive symptoms.
AB  - This study explores how grandchild care in conjunction with grandparents'
      retirement affects depressive symptoms, using data from the Health and Retirement
      Survey. The findings demonstrate that retirement moderates the influence of
      grandchild care obligations on well-being, measured by depressive symptoms. For
      retired men, freedom from grandchild care obligations is associated with
      heightened well-being. Among women, continued employment seems to protect against
      potential negative effects of extensive grandchild care obligations on well
      being. The results for men seem most in line with the argument that family care
      obligations spoil retirement, whereas the results for women suggest a scenario
      that is most compatible with the role enhancement thesis.

PMID- 16454481
TI  - The impact of support received and support provision on changes in perceived
      social support among older adults.
AB  - The current study uses longitudinal data from the 1993 U.S. Midwest floods to
      examine the influence of support received and support provision on changes in
      perceived social support among older adults exposed to an acute stressor. Results
      indicated that flood exposure and higher levels of social support at Time 1 were
      positively associated with both receiving social support and providing social
      support specific to the food. Individuals with higher levels of support provision
      and received support in turn reported higher levels of perceived support post
      disaster. Women were more likely to have received flood specific support and to
      have perceived higher social support post flood. This study provides support and
      elaboration of earlier findings that link disaster exposure to post-disaster
      changes in perceived social support.

PMID- 16454482
TI  - Older adults' coping with negative life events: common processes of managing
      health, interpersonal, and financial/work stressors.
AB  - This study examined how older adults cope with negative life events in health,
      interpersonal, and financial/work domains and whether common stress and coping
      processes hold across these three domains. On three occasions, older adults
      identified the most severe negative event they faced in the last year and
      described how they appraised and coped with that event, their ambient chronic
      stressors, and event and functioning outcomes. The stress and coping process was
      largely consistent across the three life domains. Individuals who appraised
      events as challenging and relied more on approach coping were more likely to
      report some benefit from those events. Individuals who experienced more chronic
      stressors and favored avoidance coping were more likely to be depressed and to
      have late-life drinking problems. Chronic stressors, as well as approach and
      avoidance coping, were predictably associated with overall outcomes in all three
      event domains. These findings provide a basis for preventive interventions that
      may help older adults' address the most prevalent stressors of aging more
      effectively.

PMID- 16454483
TI  - The revised CES-D scale for caregivers of the elderly in India.
AB  - The purpose of this article is to empirically determine the factor structure of
      the original Radloff's (1977) Center for Epidemiological Studies-Depression Scale
      (CES-D), on Indian caregivers of the elderly population. The CES-D was
      administered to 255 caregivers via face to face interviews. The confirmatory
      factor analysis results did not support the original four-factor theoretical
      structure, but did suggest a three-factor model. In addition the three-factor
      version showed high internal consistency among the sub scales. The results of the
      present study indicate that the revised CES-D scale reflects the difference in
      the manifestation of depression in caregivers of the elderly in the Indian
      community in Allahabad, India. This scale should be validated further by
      replication. Implications for future research are presented.

PMID- 16454485
TI  - Behavioral monitoring of trained insects for chemical detection.
AB  - A portable, handheld volatile odor detector ("Wasp Hound") that utilizes a
      computer vision system and Microplitis croceipes (Cresson) (Hymenoptera:
      Braconidae), a parasitoid wasp, as the chemical sensor was created. Five wasps
      were placed in a test cartridge and placed inside the device. Wasps were either
      untrained or trained by associative learning to detect 3-octanone, a common
      fungal volatile chemical. The Wasp Hound sampled air from the headspace of corn
      samples prepared within the lab and, coupled with Visual Cortex, a software
      program developed using the LabView graphical programming language, monitored and
      analyzed wasp behavior. The Wasp Hound, with conditioned wasps, was able to
      detect 0.5 mg of 3-octanone within a 240 mL glass container filled with feed corn
      ( approximately 2.6 x 10(-5) mol/L). The Wasp Hound response to the control (corn
      alone) and a different chemical placed in the corn (0.5 mg of myrcene) was
      significantly different than the response to the 3-octanone. Wasp Hound results
      from untrained wasps were significantly different from trained wasps when
      comparing the responses to 3-octanone. The Wasp Hound may provide a unique method
      for monitoring grains, peanuts, and tree nuts for fungal growth associated with
      toxin production, as well as detecting chemicals associated with forensic
      investigations and plant/animal disease.

PMID- 16454486
TI  - A comparison of image processing techniques for bird recognition.
AB  - Bird predation is one of the major concerns for fish culture in open ponds. A
      novel method for dispersing birds is the use of autonomous vehicles. Image
      recognition software can improve their efficiency. Several image processing
      techniques for recognition of birds have been tested. A series of morphological
      operations were implemented. We divided images into 3 types, Type 1, Type 2, and
      Type 3, based on the level of difficulty of recognizing birds. Type 1 images were
      clear; Type 2 images were medium clear, and Type 3 images were unclear. Local
      thresholding has been implemented using HSV (Hue, Saturation, and Value), GRAY,
      and RGB (Red, Green, and Blue) color models on all three sections of images and
      results were tabulated. Template matching using normal correlation and artificial
      neural networks (ANN) are the other methods that have been developed in this
      study in addition to image morphology. Template matching produced satisfactory
      results irrespective of the difficulty level of images, but artificial neural
      networks produced accuracies of 100, 60, and 50% on Type 1, Type 2, and Type 3
      images, respectively. Correct classification rate can be increased by further
      training. Future research will focus on testing the recognition algorithms in
      natural or aquacultural settings on autonomous boats. Applications of such
      techniques to industrial, agricultural, or related areas are additional future
      possibilities.

PMID- 16454487
TI  - Detection of glucose and related analytes by biosensors: a fractal analysis.
AB  - A fractal analysis is used to model the binding and dissociation kinetics of
      connective tissue interstitial glucose, adipose tissue interstitial glucose,
      insulin, and other related analytes on biosensor surfaces. The analysis provides
      insights into diffusion-limited analyte-receptor reactions occurring on
      heterogeneous biosensor surfaces. Numerical values obtained for the binding and
      the dissociation rate coefficients are linked to the degree of heterogeneity or
      roughness (fractal dimension, Df) present on the biosensor chip surface. The
      binding and dissociation rate coefficients are sensitive to the degree of
      heterogeneity on the surface. For example, for the binding of plasma insulin, as
      the fractal dimension value increases by a factor of 2.47 from Df1 equal to
      0.6827 to Df2 equal to 1.6852, the binding rate coefficient increases by a factor
      of 4.92 from k1 equal to 1.0232 to k2 equal to 5.0388. An increase in the degree
      of heterogeneity on the probe surface leads to an increase in the binding rate
      coefficient. A dual-fractal analysis is required to fit the binding kinetics in
      most of the cases presented. A single fractal analysis is adequate to describe
      the dissociation kinetics. Affinity (ratio of the binding to the dissociation
      rate coefficient) values are also presented. Interferents for glucose such as
      uric acid and ascorbic acid were also detected using glucose biosensors based on
      carbon nanotube (CNT) nanoelectrode ensembles (NEEs) (29) (Lin, Y.; Lu, F.; Tu,
      Y.; Ren, Z. Nano Lett. 2004, 4 (2), 191-195). Attempts are made to standardize
      biosensor properties in terms of diffusion characteristics on in vivo
      responsiveness.

PMID- 16454488
TI  - Biologically inspired sensing: infrared spectroscopic analysis of cell responses
      to an inhalation health hazard.
AB  - This work describes the development of a biologically based sensing technique to
      quantify chemical agents that pose inhalation health hazards. The approach
      utilizes cultured epithelial cells (A549 human type II pneumocytes) of the lung,
      exposed to potential toxins and monitored through the noninvasive means of
      infrared spectroscopy to quantify changes to cell physiology and function. Cell
      response to Streptolysin O, a cholesterol-binding cytolysin, is investigated
      here. Infrared spectra display changes in cell physiology indicative of membrane
      damage, altered proteins, and some nucleic acid damage. Methods to improve cell
      adhesion through modification of support surface properties are detailed. This
      spectroscopic approach not only provides a robust means to detect potential
      toxins but also provides information on modes of damage and mechanisms of
      cellular response.

PMID- 16454489
TI  - Liposome-doped nanocomposites as artificial-cell-based biosensors: detection of
      listeriolysin O.
AB  - Listeriolysin O (LLO) is a pore-forming hemolysin secreted by the foodborne
      pathogen Listeria monocytogenes and is required for bacterial virulence. Current
      detection methods for L. monocytogenes are time-consuming, labor-intensive, and
      expensive, which is impractical considering the limitations of food storage. To
      overcome these problems, we developed a liposome-doped silica nanocomposite as a
      simple, inexpensive, and highly stable biosensor material that mimics existing
      whole-cell assays for LLO. Small unilamellar liposomes containing fluorescent
      dyes were immobilized within porous silica using alcohol-free sol-gel synthesis
      methods. The immobilized liposomes served as cellular surrogates for membrane
      insertion and pore formation by LLO. The integrity of liposomes in the solid
      state sol-gel glass was investigated by fluorescence quenching and leaching
      assays. The materials were stable for at least 5 months in ambient conditions.
      Both free and immobilized liposomes responded to LLO at pH 6.0 with concentration
      dependent kinetics. The pore formation of LLO in liposome-doped silica composites
      displayed similar kinetic curves as free liposomes but with slower rates. LLO
      insertion into the immobilized liposomes was pH dependent. No increase in
      membrane permeability was observed at pH 7.4 for the liposome-doped composites in
      the presence of LLO. Immobilized liposomes can detect LLO in approximately 1.5 h
      using a steady state calibration and within 30 min using a kinetic calibration.
      These liposome silica composites potentially could be used for the detection of
      hemolysin producing L. monocytogenes as well as the many other bacteria that
      produce pore-forming toxins.

PMID- 16454490
TI  - A combined strategy to reduce restenosis for vascular tissue engineering
      applications.
AB  - Biodegradable polymers including poly(l-lactic acid) (PLLA) have been used to
      develop cardiovascular prostheses such as vascular grafts and stents. However,
      implant-associated thrombosis, inflammation, and restenosis are still major
      obstacles for the utility of these devices. The lack of an endothelial cell (EC)
      lining (endothelialization) on the implants and the responses of the immune
      systems toward the implants have been associated with these complications. In our
      research strategy, we have combined the drug delivery principle with the
      strategies of tissue engineering, the controlled release of anti-inflammation
      drugs and enhanced endothelialization, to reduce the implant-associated adverse
      responses. We first integrated curcumin, an anti-inflammatory drug and anti
      smooth muscle cell (SMC) proliferative drug, with PLLA. This curcumin-loaded PLLA
      material was then modified using adsorptive coating of adhesive proteins such as
      fibronectin, collagen-I, vitronectin, laminin, and matrigel to improve the
      endothelial cell (EC) adhesion and proliferation, and ECs were seeded on top of
      these modified surfaces. Our results showed steady drug release kinetics over the
      period of 50 days from curcumin-loaded PLLA materials. Additionally, integration
      of curcumin in PLLA increased the roughness of the scaffold at the nanometric
      scale using an atomic force microscopic analysis. Moreover, coating with
      fibronectin on curcumin-loaded PLLA surfaces gave the highest EC adhesion and
      proliferation compared to other adhesive proteins using PicoGreen DNA assays. The
      ability of our strategy to release the curcumin for producing anti-inflammation
      and anti-proliferation responses and to improve EC adhesion and growth after EC
      seeding suggests this strategy may reduce implant-associated adverse responses
      and be a better approach for vascular tissue engineering applications.

PMID- 16454491
TI  - Potent and specific inhibition of retrovirus production by coexpression of
      multiple siRNAs directed against different regions of viral genomes.
AB  - siRNA-mediated RNA degradation has been demonstrated to act as an antiviral
      system in many species. Here we describe inhibition of retrovirus production by
      multiple siRNAs designed to target various regions of the viral genomes. Using
      murine leukemia virus (MuLV) as a model, we demonstrate that the virus production
      can be inhibited by 77% in siLTR2 (a siRNA targeting the U3 region of MuLV)
      expression vector transfected cells. Coexpression of siLTR2 with siPsi2 (a siRNA
      targeting the 3' Psi (packaging signal sequence) results in 93% suppression of
      the virus production, suggesting that an increased inhibition of the virus
      production can be achieved by coexpression of multiple siRNAs to target different
      regions of the viral RNA simultaneously. Our results also indicate that not all
      sequences of the viral RNA are equally accessible to siRNA. We show that U3
      region of MuLV is more accessible to siRNA, whereas the packaging signal
      sequence, especially the region adjacent to 5'LTR, is less accessible to siRNA,
      partly as a result of the binding of Gag precursors. Furthermore, we demonstrate
      that coexpression of siLTR2 with siPsi2 in virus producer cells leads to 88%
      knockdown of viral titer, showing the benefit of coexpression of multiple siRNAs
      for potent suppression of virus production in the setting of an established
      infection. Moreover, we demonstrate that infection of MuLV in cells that stably
      coexpress siLTR2 with siPsi2 diminishes by 77%. Taken together, we establish that
      siRNA-mediated gene silencing can suppress multiple steps of the retrovirus life
      cycle, offering a potential for both treating virus-associated diseases and
      preventing viral infection.

PMID- 16454492
TI  - Screening of thermophilic anaerobic bacteria for solid substrate cultivation on
      lignocellulosic substrates.
AB  - Interest in solid substrate cultivation (SSC) techniques is gaining for
      biochemical production from renewable resources; however, heat and mass transfer
      problems may limit application of this technique. The use of anaerobic
      thermophiles in SSC offers a unique solution to overcoming these challenges. The
      production potential of nine thermophilic anaerobic bacteria was examined on corn
      stover, sugar cane bagasse, paper pulp sludge, and wheat bran in submerged liquid
      cultivation (SmC) and SSC. Production of acetate, ethanol, and lactate was
      measured over a 10 day period, and total product concentrations were used to
      compare the performance of different organism-substrate combinations using the
      two cultivation methods. Overall microbial activity in SmC and SSC was dependent
      on the organism and growth substrate. Clostridium thermocellum strains JW20,
      LQRI, and 27405 performed significantly better in SSC when grown on sugar cane
      bagasse and paper pulp sludge, producing at least 70 and 170 mM of total
      products, respectively. Growth of C. thermocellum strains in SSC on paper pulp
      sludge proved to be most favorable, generating at least twice the concentration
      of total products produced in SmC (p-value < 0.05). Clostridium thermolacticum
      TC21 demonstrated growth on all substrates producing 30-80 and 60-116 mM of total
      product in SmC and SSC, respectively. Bacterial species with optimal growth
      temperatures of 70 degrees C grew best on wheat bran in SmC, producing total
      product concentrations of 45-75 mM. For some of the organism-substrate
      combinations total end product concentrations in SSC exceeded those in SmC,
      indicating that SSC may be a promising alternative for microbial activity and
      value-added biochemical production.

PMID- 16454493
TI  - Effects of oxygen on aerobic solid-state biodegradation kinetics.
AB  - Oxygen is a critical control variable for composting and other solid-state
      biodegradation processes. In this study we examined the effect of varying oxygen
      concentrations (1%, 4%, and 21% O2 (v/v)) on biodegradation kinetics under
      different substrate (sewage sludge and synthetic food waste), temperature (35,
      45, 55, and 65 degrees C), and moisture (36-60% H2O) conditions. Three forms of a
      saturation or Monod-type model and one form of an exponential model were
      evaluated against data from extensive experiments under carefully controlled
      environmental conditions. The exponential model performed well at temperatures
      from 35 to 55 degrees C but had problems at higher temperatures. The Monod-type
      models yielded the best fit based on R2 values. Multiple linear regression was
      used to express the oxygen half-saturation coefficient as a function of
      temperature and moisture. For a modified one-parameter saturation model the half
      saturation coefficient varied from -0.67% to 1.74% v/v O2 under the range of
      conditions typical of composting systems. While the positive correlation of
      biodegradation rate with oxygen concentration reported by previous researchers
      held true for temperatures below 55 degrees C, an inverse relationship was found
      at 65 degrees C. Although this study did not directly examine anaerobic
      conditions, the results under microaerophilic conditions suggest oxygen may not
      offer kinetic advantages for extreme thermophilic biodegradation processes.

PMID- 16454494
TI  - Modeling the temperature kinetics of aerobic solid-state biodegradation.
AB  - This study evaluated three models of microbial temperature kinetics using CO2
      respiration data from aerobic solid-state biodegradation experiments. The models
      included those of Andrews and Kambhu/Haug, Ratkowsky et al., and the Cardinal
      Temperature Model with Inflection (CTMI) of Rosso et al. A parameter estimation
      routine implemented the Complex-Box search method for each model on 48 data sets
      collected during the composting of synthetic food waste or sewage-sludge
      (biosolids) mixed with maple wood chips at different oxygen concentrations and
      extents of decomposition. Each of the three nonlinear temperature kinetic
      functions proved capable of modeling a wide range of experimental data sets.
      However, the models differed widely in the consistency of their parameters.
      Parameters in the CTMI model were more stable over the course of the degradation
      process, and that variability which did arise was directly related to changes in
      the microbial process. Additional benefits of the CTMI model include the ease of
      parameter determinations, which can be approximated directly from laboratory
      experiments or full-scale system analysis, and the direct value of its parameters
      in engineering design and process control under a wide range of biodegradation
      conditions.

PMID- 16454495
TI  - Ensiling corn stover: effect of feedstock preservation on particleboard
      performance.
AB  - Ensilage is a truncated solid-state fermentation in which anaerobically produced
      organic acids accumulate to reduce pH and limit microbial activity. Ensilage can
      be used to both preserve and pretreat biomass feedstock for further downstream
      conversion into chemicals, fuels, and/or fiber products. This study examined the
      ensilage of enzyme-treated corn stover as a feedstock for particleboard
      manufacturing. Corn stover at three different particle size ranges (<100, <10,
      and <5 mm) was ensiled with and without a commercial enzyme mixture having a
      cellulase:hemicellulase ratio of 2.54:1, applied at a hemicellulase rate of 1670
      IU/kg dry mass. Triplicate 20 L mini-silos were destructively sampled and
      analyzed on days 0, 1, 7, 21, 63, and 189. Analysis included produced organic
      acids and water-soluble carbohydrates, fiber fractions, pH, and microorganisms,
      including Lactobacillus spp. and clostridia were monitored. On days 0, 21, and
      189, the triplicate samples were mixed evenly and assembled into particleboard
      using 10% ISU 2 resin, a soy-based adhesive. Particleboard panels were subjected
      to industry standard tests for modulus of rupture (MOR), modulus of elasticity
      (MOE), internal bonding strength (IB), thickness swell (TS), and water absorption
      at 2 h boiling and 24 h soaking. Enzyme addition did improve the ensilage
      process, as indicated by sustained lower pH (P < 0.0001), higher water-soluble
      carbohydrates (P < 0.05), and increased lactic acid production (P < 0.0001). The
      middle particle size range (<10 mm) demonstrated the most promising results
      during the ensilage process. Compared with fresh stover, the ensilage process did
      increase IB of stover particleboard by 33% (P < 0.05) and decrease water
      adsorption at 2 h boiling and 24 h soaking significantly (P < 0.05).
      Particleboard panels produced from substrate ensiled with enzymes showed a
      significant reduction in water adsorption of 12% at 2 h boiling testing. On the
      basis of these results, ensilage can be used as a long-term feedstock
      preservation method for particleboard production from corn stover. Enzyme-amended
      ensilage not only improved stover preservation but also enhanced the properties
      of particleboard products.

PMID- 16454496
TI  - Semantic retrieval in DNA-based memories with Gibbs energy models.
AB  - At least three types of associative memories based on DNA-affinity have been
      proposed. Previously, we have quantified the quality of retrieval of genomic and
      abiotic information in simulation by comparison to state-of-the-art symbolic
      methods available, such as LSA (Latent Semantic Analysis). Their performance is
      poor when the evaluation criterion for DNA-affinity is a simple approximation of
      the Gibbs energy that governs duplex formation for retrievals. Here, we use a
      more realistic approximation of the Gibbs energy to improve semantic retrievals
      in DNA memories. Their performance is much closer to that of LSA, according to
      human expert ratings. With more realistic approximations of DNA affinity,
      performance is expected to improve for other, more adaptive associative memories
      with compaction in silico, and even more so with actual DNA molecules in vitro.

PMID- 16454497
TI  - Functionalization of gold and glass surfaces with magnetic nanoparticles using
      biomolecular interactions.
AB  - Advances in nanotechnology have enabled the production and characterization of
      magnetic particles with nanometer-sized features that can be functionalized with
      biological recognition elements for numerous applications in biotechnology. In
      the present study, the synthesis of and interactions between self-assembled
      monolayers (SAMs) on gold and glass surfaces and functionalized magnetic
      nanoparticles have been characterized. Immobilization of 10-15 nm streptavidin
      functionalized nanoparticles to biotinylated gold and glass surfaces was achieved
      by the strong interactions between biotin and streptavidin. Fluorescent
      streptavidin-functionalized nanoparticles, biotinylated surfaces, and
      combinations of the two were characterized by Fourier transform infrared
      spectroscopy, X-ray photoelectron spectroscopy, and electron and fluorescent
      microscopy to confirm that little or no functionalization occurred in
      nonbiotinylated regions of the gold and glass surfaces compared to the
      biotinylated sites. Together these techniques have potential use in studying the
      modification and behavior of functionalized nanoparticles on surfaces in
      biosensing and other applications.

PMID- 16454498
TI  - Numerical analysis of muscle-like ionic polymer actuators.
AB  - Ionic polymers are a promising material for the development of muscle-like
      actuators. These materials are capable of undergoing significant deformation when
      structured as metal-polymer-metal composite sheets. The mechanical
      characteristics of these sheets, such as flexibility, softness, and ability to
      undergo large deformation in direct contact with water, have led some to consider
      these as possible artificial muscles. This paper describes the numerical analysis
      of an electrochemical model of the deformation of muscle-like polymers. A general
      continuum model describing the transport and deformation processes of these
      actuators is briefly presented, along with a detailed description of the
      simulation scheme used to predict deformation, current, and mass transport. The
      predictions of the model are compared with experimental data, indicating a
      significant role of water transport in the large-scale deformation. The model is
      also used to draw a comparison between the performance of natural muscles and
      muscle-like polymer actuators.

PMID- 16454499
TI  - Fluorescent biorecognition of gold nanoparticle-IgG conjugates self-assembled on
      E-beam patterns.
AB  - A new concept for line patterning of immunoglobulin G (IgG) in nanometer scale
      using gold nanoparticles (AuNPs) self-assembled in a nanochannel written with an
      electron beam is proposed and demonstrated. AuNPs are synthesized by reducing
      KAuCl4 with NaBH4, producing AuNPs 40-70 nm in size, where Cl- ions are capping
      AuNPs thus making them negatively charged and subsequently stabilized. IgG is
      conjugated to these AuNPs by simple adsorption. Single or multiple nanochannels
      are written with an electron beam using a scanning electron microscope (SEM) in a
      layer of poly(methyl methacrylate) (PMMA), which is spin-coated on a p-doped Si
      wafer. AuNPs bind into the etched nanochannel where the Si surface is exposed,
      while the relatively hydrophobic PMMA area repels the particles. The particles
      with a diameter larger than the channel width are not able to go inside of it.
      Anti-IgG, conjugated with fluorescein isothiocyanate (FITC), is then exposed to
      the patterned surface, binding specifically to the IgG-AuNP conjugates within the
      line patterns. These antibody-antigen bindings can be visualized with a
      fluorescent microscope, showing the fluorescent signal only along with the
      nanometer line pattern. These initial steps will lead to the formation of complex
      protein nanoarrays, based on the size-dependent self-assembly of AuNPs within
      variously sized nanopatterns.

PMID- 16454500
TI  - Structural stability of polypeptide nanofilms under extreme conditions.
AB  - Self-assembly of designed peptides is a promising area of biomaterials research
      and development. Here, polypeptide nanofilms have been prepared by electrostatic
      layer-by-layer self-assembly (LBL) of cysteine (Cys)-containing 32mers designed
      to be oppositely charged at neutral pH, and structural stability of the films has
      been probed by subjecting them to various extreme physical and chemical
      conditions. The results suggest that although electrostatic attraction plays a
      key role in strengthening polypeptide films, stability is inversely related to
      absolute net charge of the supramolecular complex. This behavior is similar to
      the typical behavior of small globular proteins. Film structure is very stable in
      organic solvent and, when dehydrated, at extreme temperatures. Such stability is
      in marked contrast to the behavior of proteins, which tend to denature under
      comparable conditions. Similar to proteins, peptide nanofilms cross-linked by
      disulfide (S-S) bonds are considerably stronger than films stabilized by
      electrostatic, van der Waals, or hydrophobic interactions alone. This effect is
      particularly evident at extremes of pH and at elevated temperature when the film
      is hydrated. These results, the great variety of possible peptide structures, the
      inherent biocompatibility of l-amino acids, and current applications of thin
      films in commercial products together suggest that polypeptide films are
      promising for the development of new or enhanced products in food technology,
      drug delivery and medical device coatings, and biomaterials.

PMID- 16454501
TI  - Development of a temperature-sensitive composite hydrogel for drug delivery
      applications.
AB  - To develop materials with improved controllability and specificity, we have
      investigated composite hydrogels with temperature-sensitive properties using
      photo cross-linking. Specifically, our novel composite materials are composed of
      nanoparticles made of poly(N-isopropylacrylamide) (PNIPAAm), temperature
      sensitive hydrogels, and a photo cross-linker, poly(ethylene glycol) diacrylate
      (PEGDA). PNIPAAm particles were synthesized by emulsion polymerization and by
      varying concentration of four main factors: monomers (N-isopropylacrylamide),
      cross-linkers (N,N'-methylenebisacrylamide), surfactants (sodium dodecyl sulfate,
      SDS), and initiators (potassium persulfate). We found that the surfactant, SDS,
      was the most important factor affecting the particle size using the factorial
      design analysis. Additionally, both nano- and micro-PNIPAAm particles had
      excellent loading efficiency (>80% of the incubated bovine serum albumin (BSA)),
      and their release kinetics expressed an initial burst effect followed by a
      sustained release over time. Furthermore, BSA-loaded PNIPAAm nanoparticles were
      used to form three-dimensional gel networks by means of a photocuring process
      using a photo cross-linker, PEGDA, and a photoinitiator, Irgacure-2959 (I-2959).
      Results from scanning electron microscopy and in vitro BSA release studies from
      these hydrogels demonstrated that PNIPAAm nanoparticles were embedded inside the
      PEG polymeric matrix and the composite material was able to release BSA in
      response to changes in temperature. These PNIPAAm nanoparticle hydrogel networks
      may have advantages in applications of controlled drug delivery systems because
      of their temperature sensitivity and their ability of in situ photopolymerization
      to localize at the specific region in the body.

PMID- 16454502
TI  - Fine tuning of physical properties of designed polypeptide multilayer films by
      control of pH.
AB  - Adjustment of pH can alter the ensemble of three-dimensional structures of a
      polypeptide in solution by changing the distribution of charge and Coulombic
      interactions. The role of pH in layer-by-layer self-assembly (LbL) of designed
      32mer peptides containing the amino acid cysteine has been investigated using a
      combination of physical methods. Results show that pH can have a substantial
      influence on the mass of adsorbed peptide, surface roughness, and film density
      over a range of 1.5 pH units. Peptide film thickness depends on the number of
      layers, as with "conventional" polyelectrolytes. Film density and morphology,
      however, vary more with pH than does thickness, translating into a change in
      density on the order of 70% over the pH range 7.4-8.9. Results of this work
      provide insight on the physical basis of LbL and suggest that peptides are a
      promising class of polyelectrolytes for the creation of designer thin films for
      applications in biotechnology and other areas.

PMID- 16454503
TI  - Neurite development in PC12 cells on flexible micro-textured substrates under
      cyclic stretch.
AB  - We investigated the combined effect of micro-texture and mechanical strain on
      neuronal cell development such as neurite length and neurite density in a rat
      pheochromocytoma cell line (PC12 cells). Cells were seeded on flexible silicone
      substrates with micro-texture or no texture (smooth) and cultured under static
      and dynamic conditions. In the static condition substrates were not stretched and
      in the dynamic conditions substrates were subjected to cyclic uniaxial stretching
      at three different strain levels of 4%, 8%, and 16% with each at three different
      strain rates at 0.1, 0.5, and 1.0 Hz. Results showed that of all cell cultures
      there was no significant difference in neurite development between cells on
      smooth and textured substrates, except in the static and 4% at 0.1 Hz conditions,
      where micro-texture induced significantly longer neurites. With both types of
      substrates, a lower mechanical condition (4% at 1.0 Hz or 16% at 0.1 Hz) resulted
      in more and longer neurites and lower cell density, and a higher mechanical
      condition (16% at 1.0 Hz) resulted in fewer and shorter neurites and lower cell
      density as compared to the static condition. These findings suggest that the
      effect of the micro-texture on neurite development is more prominent in low
      mechanical conditions than in high mechanical conditions and that the strain
      level and strain rate have an interrelated effect on neurite development: a
      higher strain level at a lower strain rate has a similar effect as a lower strain
      level at a higher strain rate in terms of promoting neurite development.

PMID- 16454504
TI  - Molding mineral within microporous hydrogels by a polymer-induced liquid
      precursor (PILP) process.
AB  - Natural biominerals often have exquisite morphologies, where the cells exercise a
      high degree of crystallographic control through secretion of biological
      macromolecules and regulation of ion transport. One important example is the sea
      urchin spine. It has recently been shown to be formed through deposition of a
      transient amorphous calcium carbonate (ACC) precursor phase that later transforms
      to single-crystalline calcite, ultimately forming an elaborate three-dimensional
      microporous calcium carbonate structure with interconnected pores. Macromolecules
      associated with the mineral phase are thought to play a key role in regulating
      this transformation. The work described here mimics this type of morphological
      control by "molding" an amorphous calcium carbonate precursor within a porous
      poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel that has been prepared as a
      negative replica from the void space of an urchin spine. Using an acidic
      biomimetic polymer as a process-directing agent, we show that polyaspartic acid
      induces amorphous calcium carbonate (ACC) nanoparticles, which have fluidic
      character and therefore are able to infiltrate the PHEMA hydrogel replica and
      coalesce into the convoluted morphology that replicates the original microporous
      structure of the sea urchin spine. By "molding" calcium carbonate into a complex
      morphology at room temperature, using a precursor process that is induced by a
      biomimetic acidic macromolecule, the PILP process is a useful in vitro model for
      examining different aspects of the amorphous-to-crystalline transformation
      process that is apparently used by a variety of biomineralizing organisms. For
      example, although we were able to replicate the overall morphology of the spine,
      it had polycrystalline texture; further studies with this system will focus on
      controlling the nucleation event, which may help to elucidate how such a
      convoluted structure can be prepared with single-crystalline texture via an
      amorphous precursor. Through a better understanding of the mechanisms used by
      organisms to regulate crystal properties, such biomimetic processes can lead to
      the synthesis of materials with superior electronic, mechanical, and optical
      properties.

PMID- 16454505
TI  - Protein insertion and patterning of PEG bearing langmuir monolayers.
AB  - Protein adsorption to multicomponent lipid monolayers is presented as a means of
      inducing protein-specific binding pockets or imprints in membranes. Adsorption of
      the acidic protein ferritin to Langmuir monolayers of cationic
      dioctadecyldimethylammonium bromide (DOMA), nonionic methyl stearate (SME), and
      poly(ethylene glycol) (PEG) bearing phospholipids is investigated as a model
      system. The number, size, and distribution of protein binding pockets (domains of
      SME and DOMA in a PEG matrix) are defined by controlling the molar ratios,
      miscibility, and lateral mobility of the lipids. Protein patterning of binary
      SME:DOMA monolayers is limited by protein-protein interactions that hinder
      desorption to regenerate the imprint site. The incorporation of PEG bearing
      phospholipids as a third lipid component provides a successful approach to
      prevent protein surface aggregation during imprinting. Atomic force microscopy
      reveals a user-defined distribution of protein molecules where protein-protein
      interactions on the monolayer are eliminated, thus facilitating protein
      desorption and regeneration of the protein binding pockets.

PMID- 16454506
TI  - Macroecology: the organizing forces.
AB  - The fundamental problem in ecology is the relationship between organisms and the
      physical world. This question is approached through the study of ecosystems as
      wholes. Pristine, autonomous Arctic lakes provide an invaluable starting point
      for such investigations. Studies on these lakes, initiated in 1958, indicate that
      the dominant fish populations assume a recognizable and repeatable structure,
      which if not disturbed by external forces, is maintained indefinitely. The
      observable characteristics are high biomass, large individual size, great age,
      uniformity of individuals despite great variation in age, and relatively few
      juveniles. This configuration expresses a state of least specific energy
      dissipation or least specific entropy production and may be regarded as a
      standing wave in the energy flow. Similar characteristics were found in the
      dominant species in a wide range of ecosystems worldwide. A state of least
      dissipation develops when two energy transport processes interfere with each
      other in the vicinity of thermodynamic equilibrium. Thus it is postulated that
      living organisms originated through the agonistic interaction between two energy
      transport processes within materials, initially occurring in an environment close
      to thermodynamic equilibrium. These two processes, fundamental to energy
      transfer, are recognized as the principle of least action and its diametrical
      opposite, the principle of most action. Each force dominates system behavior in a
      different time frame: most action in the short-term (ecological time) and least
      action over the long-term (evolutionary time). Interaction between the
      countervailing forces provides an understanding of a wide range of emergent
      ecological generalities such as succession, r- and K-selection, the stability and
      diversity of ecosystems, and the directionality of evolutionary change.

PMID- 16454507
TI  - Change is necessary in a biological engineering curriculum.
AB  - Success of a Biological Engineering undergraduate educational program can be
      measured in a number of ways, but however it is measured, a presently successful
      program can translate into an unsuccessful program if it cannot adjust to
      different conditions posed by technical advances, student characteristics, and
      academic pressures. Described in this paper is a Biological Engineering
      curriculum that has changed significantly since its transformation from
      Agricultural Engineering in 1993. As a result, student numbers have continued to
      climb, specific objectives have emerged, and unique courses have been developed.
      The Biological Resources Engineering program has evolved into a program that
      emphasizes breadth, fundamentals, communications skills, diversity, and practical
      engineering judgment.

PMID- 16454508
TI  - Problem-based learning biotechnology courses in chemical engineering.
AB  - We have developed a series of upper undergraduate/graduate lecture and laboratory
      courses on biotechnological topics to supplement existing biochemical
      engineering, bioseparations, and biomedical engineering lecture courses. The
      laboratory courses are based on problem-based learning techniques, featuring two-
      and three-person teams, journaling, and performance rubrics for guidance and
      assessment. Participants initially have found them to be difficult, since they
      had little experience with problem-based learning. To increase enrollment, we are
      combining the laboratory courses into 2-credit groupings and allowing students to
      substitute one of them for the second of our 2-credit chemical engineering unit
      operations laboratory courses.

PMID- 16454509
TI  - An introduction to simulation and visualization of biological systems at multiple
      scales: a summer training program for interdisciplinary research.
AB  - Advances in biomedical research require a new generation of researchers having a
      strong background in both the life and physical sciences and a knowledge of
      computational, mathematical, and engineering tools for tackling biological
      problems. The NIH-NSF Bioengineering and Bioinformatics Summer Institute at the
      University of Pittsburgh (BBSI @ Pitt; www.ccbb.pitt.edu/bbsi) is a multi
      institutional 10-week summer program hosted by the University of Pittsburgh,
      Duquesne University, the Pittsburgh Supercomputing Center, and Carnegie Mellon
      University, and is one of nine Institutes throughout the nation currently
      participating in the NIH-NSF program. Each BBSI focuses on a different area; the
      BBSI @ Pitt, entitled "Simulation and Computer Visualization of Biological
      Systems at Multiple Scales", focuses on computational and mathematical approaches
      to understanding the complex machinery of molecular-to-cellular systems at three
      levels, namely, molecular, subcellular (microphysiological), and cellular. We
      present here an overview of the BBSI @ Pitt, the objectives and focus of the
      program, and a description of the didactic training activities that distinguish
      it from other traditional summer research programs. Furthermore, we also report
      several challenges that have been identified in implementing such an
      interdisciplinary program that brings together students from diverse academic
      programs for a limited period of time. These challenges notwithstanding,
      presenting an integrative view of molecular-to-system analytical models has
      introduced these students to the field of computational biology and has allowed
      them to make an informed decision regarding their future career prospects.

PMID- 16454510
TI  - Role of Caco-2 cell monolayers in prediction of intestinal drug absorption.
AB  - The usefulness of Caco-2 cell monolayers in determining the intestinal drug
      absorption of potential drug candidates as such and from delivery systems,
      elucidating the underlying mechanisms thereof, presystemic metabolism, cellular
      uptake and cytotoxicological assessment has been exemplified in this review. The
      role of Caco-2 cell monolayers in studying the effectiveness, involved mechanism
      and toxicity of various excipients for drug absorption promotion has also been
      discussed.

PMID- 16454511
TI  - Influence of C18 long chain fatty acids on hydrogen metabolism.
AB  - During anaerobic treatment, several microorganisms mediate a series of reactions
      to convert reduced compounds (electron donors) into methane. Inhibitors such as
      long chain fatty acids (LCFAs) can affect several anaerobic microbial populations
      and decrease the treatment efficiency. The effects of three C18 LCFAs on
      hydrogenotrophic methanogens in a flocculated mixed anaerobic culture were
      assessed in this study. The reaction half-life and the hydrogen versus time
      profiles were used to characterize the inhibition process. The half-life values
      and profiles were similar for controls and cultures exposed to LCFAs for 1 h. The
      hydrogen inhibition was a function of the exposure time and the LCFA
      concentration except for cultures exposed to stearic acid (SA). A statistical
      analysis of the reaction half-life for cultures incubated with 1,500 and 2,000 mg
      L(-1) LCFAs for 48 h, revealed the following inhibition trend: linoleic acid (LA)
      > oleic acid (OA) > SA. After 48 h of exposure, no clear inhibition trend was
      observed for cultures inoculated with LCFA mixtures; however, at levels of 1,500
      and 2,000 mg L(-1), the reaction half-life values were less than that observed
      for cultures fed with only LA. Based on the reaction half-life data, all of the
      LCFAs except SA at threshold levels of approximately 1,500 mg L(-1) inhibited
      hydrogen metabolism. The greatest inhibition and, hence, the largest amount of
      accumulated hydrogen was observed in cultures fed with 2,000 mg L(-1) LA and
      incubated for 48 h.

PMID- 16454512
TI  - TNT phytotransformation pathway characteristics in Arabidopsis: role of aromatic
      hydroxylamines.
AB  - Basic knowledge of the plant transformation pathways of TNT will aid
      phytoremediation design and assessment. While TNT transformation by plant
      metabolism has been demonstrated in previous studies, the presence and role of
      hydroxylamines in the transformation pathway has not been sufficiently
      understood. Hydroxylamines are unequivocally shown to be formed by plant
      transformation of TNT by two axenic plant systems (Arabidopsis thaliana and
      Catharanthusroseus). In addition, confirmation was obtained for conversion of
      these hydroxylamines to previously identified conjugates. Further characteristics
      of TNT transformation in Arabidopsis, an increasingly popular model system for
      genetic and biochemical studies of TNT transformation, were elucidated by [U
      14C]TNT mass balance studies and metabolite feeding studies. These studies showed
      the rapid conversion of TNT to unextractable bound compounds by Arabidopsis
      seedlings in agreement with the green-liver model. Arabidopsis seedlings formed
      and transformed 4-substituted metabolites more efficiently than the 2-substituted
      metabolites. A qualitative kinetic rate analysis of the pathway was performed to
      propose rate-limiting steps in the pathway and theoretical schemes for improved
      rates are suggested.

PMID- 16454513
TI  - Evaluation of culture medium for nisin production in a repeated-batch biofilm
      reactor.
AB  - In this study, a biofilm reactor with plastic composite support (PCS), made by
      high-temperature extrusion of agricultural products and polypropylene, was
      evaluated for nisin production using L. lactis strain NIZO 22186. The high
      biomass density of the biofilm reactor was found to contribute to a significantly
      shorter lag time of nisin production relative to a suspended-cell reactor. In
      comparison to glucose (579 IU/mL), sucrose significantly increased the nisin
      production rate by 1.4-fold (1100 IU/mL). However, results revealed that high
      levels of sucrose (8% w/v) had a suppressing effect on nisin production and a
      stimulating effect on lactic acid production. A high concentration of MgSO4.7H2O
      at 0.04% (w/v) was found to reduce the nisin production, while concentrations of
      KH2PO4 of up to 3% (w/v) did not have any significant effect on growth or nisin
      production. The best of the tested complex media for nisin production using the
      PCS biofilm reactor consisted of 4% (w/v) sucrose, 0.02% (w/v) MgSO4.7H2O, and
      0.1% (w/v) KH2PO4. Nisin production rate in the biofilm reactor was significantly
      increased by 3.8-fold (2208 IU/mL) when using the best complex medium tested.

PMID- 16454514
TI  - Surfactant-induced unfolding of cellulase: kinetic studies.
AB  - Surfactant-induced unfolding is a significant degradation pathway for detergent
      enzymes. This study examines the kinetics of surfactant-induced unfolding for
      endoglucanase III, a detergent cellulase, under conditions of varying pH,
      temperature, ionic strength, surfactant type, and surfactant concentration.
      Interactions between protein and surfactant monomer are shown to play a key role
      in determining the kinetics of the unfolding process. We demonstrate that the
      unfolding rate can be slowed by (1) modifying protein charge and/or pH conditions
      to create electrostatic repulsion of ionic surfactants and (2) reducing the
      amount of monomeric ionic surfactant available for interaction with the enzyme
      (i.e., by lowering the critical micelle concentration). Additionally, our results
      illustrate that there is a poor correlation between thermodynamic stability in
      buffer (DeltaG(unfolding)) and resistance to surfactant-induced unfolding.

PMID- 16454515
TI  - Rapid optimization of antibotulinum toxin antibody fragment production by an
      integral approach utilizing RC-SELDI mass spectrometry and statistical design.
AB  - A process for the rapid development and optimization of the fermentation process
      for an antibotulinum neurotoxin antibody fragment (bt-Fab) production expressed
      in Escherichia coli was achieved via a high-throughput process proteomics and
      statistical experimental design. This process, using retentate chromatography
      surface enhanced laser desorption/ionization mass spectrometry (RC-SELDI MS), was
      employed for identifying and quantifying bt-Fab antibody in complex biological
      samples for the optimization of microbial fermentation conditions. Five variables
      (type of culture media, glycerol concentration, post-induction temperature, IPTG
      concentration, and incubation time after induction) were statistically combined
      using an experimental 2(5)(-1) fractional factorial design and tested for their
      effects on maximal bt-Fab antibody production. When the effects of individual
      variables and their interactions were assessed, type of media and post-induction
      temperature showed statistically significant increase in yield of the
      fermentation process for the maximal bt-Fab antibody production. This study
      establishes an integral approach as a valuable tool for the rapid development of
      manufacturing processes for producing various biological materials. To verify the
      RC-SELDI MS method, a Fab-specific immuno-affinity HPLC assay developed here was
      also employed for the quantification of the bt-Fab antibody in crude lysate
      samples obtained during the fermentation optimization process. Similar results
      were obtained.

PMID- 16454516
TI  - A comparison of air and hydrogen peroxide oxygenated microbial fuel cell
      reactors.
AB  - In this study, a two-compartment continuous flow microbial fuel cell (MFC)
      reactor was used to compare the efficiencies of cathode oxygenation by air and by
      hydrogen peroxide. The MFC reactor had neither a proton-selective membrane nor an
      electron transfer mediator. At startup, the cathodic compartment was continuously
      aerated and the anodic compartment was fed with a glucose solution. An increase
      of electrical power generation from 0.008 to 7.2 mW m(-2) of anode surface with a
      steady-state potential of 215-225 mV was observed within a period of 12 days. The
      performance of the air-oxygenated MFC reactor progressively declined over time
      because of biofilm proliferation in the cathodic compartment. Oxygenation of the
      cathodic compartment using 300 mL d(-1) of 0.3% hydrogen peroxide solution
      resulted in a power density of up to 22 mW m(-2) (68.2 mA m(-2)) of anode surface
      at a potential of 340-350 mV. The use of H2O2 for oxygenation was found to
      improve the long-term stability of the MFC reactor.

PMID- 16454517
TI  - Bioprocess iterative batch-to-batch optimization based on hybrid
      parametric/nonparametric models.
AB  - This paper presents a novel method for iterative batch-to-batch dynamic
      optimization of bioprocesses. The relationship between process performance and
      control inputs is established by means of hybrid grey-box models combining
      parametric and nonparametric structures. The bioreactor dynamics are defined by
      material balance equations, whereas the cell population subsystem is represented
      by an adjustable mixture of nonparametric and parametric models. Thus
      optimizations are possible without detailed mechanistic knowledge concerning the
      biological system. A clustering technique is used to supervise the reliability of
      the nonparametric subsystem during the optimization. Whenever the nonparametric
      outputs are unreliable, the objective function is penalized. The technique was
      evaluated with three simulation case studies. The overall results suggest that
      the convergence to the optimal process performance may be achieved after a small
      number of batches. The model unreliability risk constraint along with sampling
      scheduling are crucial to minimize the experimental effort required to attain a
      given process performance. In general terms, it may be concluded that the
      proposed method broadens the application of the hybrid parametric/nonparametric
      modeling technique to "newer" processes with higher potential for optimization.

PMID- 16454518
TI  - Stochastic models to study the impact of mixing on a fed-batch culture of
      Saccharomyces cerevisiae.
AB  - The mechanisms of interaction between microorganisms and their environment in a
      stirred bioreactor can be modeled by a stochastic approach. The procedure
      comprises two submodels: a classical stochastic model for the microbial cell
      circulation and a Markov chain model for the concentration gradient calculus. The
      advantage lies in the fact that the core of each submodel, i.e., the transition
      matrix (which contains the probabilities to shift from a perfectly mixed
      compartment to another in the bioreactor representation), is identical for the
      two cases. That means that both the particle circulation and fluid mixing process
      can be analyzed by use of the same modeling basis. This assumption has been
      validated by performing inert tracer (NaCl) and stained yeast cells dispersion
      experiments that have shown good agreement with simulation results. The
      stochastic model has been used to define a characteristic concentration profile
      experienced by the microorganisms during a fermentation test performed in a scale
      down reactor. The concentration profiles obtained in this way can explain the
      scale-down effect in the case of a Saccharomyces cerevisiae fed-batch process.
      The simulation results are analyzed in order to give some explanations about the
      effect of the substrate fluctuation dynamics on S. cerevisiae.

PMID- 16454519
TI  - Effect of cellulase mole fraction and cellulose recalcitrance on synergism in
      cellulose hydrolysis and binding.
AB  - Elucidating the molecular mechanisms that govern synergism is important for the
      rational engineering of cellulase mixtures. Our goal was to observe how varying
      the loading molar ratio of cellulases in a binary mixture and the recalcitrance
      of the cellulose to enzymatic degradation influenced the degree of synergistic
      effect (DSE) and degree of synergistic binding (DSB). The effect of cellulose
      recalcitrance was studied using a bacterial microcrystalline cellulose (BMCC),
      which was exhaustively hydrolyzed by a catalytic domain of Cel5A, an
      endocellulase. The remaining prehydrolyzed BMCC (PHBMCC) was used to represent a
      recalcitrant form of cellulose. DSE was observed to be sensitive to loading molar
      ratio. However, on the more recalcitrant cellulose, synergism decreased.
      Furthermore, the results from this study reveal that when an exocellulase (Cel6B)
      is mixed with either an endocellulase (Cel5A) or a processive endocellulase
      (Cel9A) and reacted with BMCC, synergism is observed in both hydrolysis and
      binding. This study also revealed that when a "classical" endocellulase (Cel5A)
      and a processive endocellulase (Cel9A) are mixed and reacted with BMCC, only
      limited synergism is observed in reducing sugar production; however, binding is
      clearly increased by the presence of the Cel5A.

PMID- 16454520
TI  - Development of a transient segregated mathematical model of the semicontinuous
      microbial production process of dihydroxyacetone.
AB  - For the mathematical description of the semicontinuous two-stage repeated-fed
      batch fermentation of dihydroxyacetone (DHA), a novel segregated model
      incorporating transient growth rates was developed. The fermentation process was
      carried out in two stages. A viable, not irreversibly product-inhibited culture
      was maintained in the first reactor stage until a predetermined DHA threshold
      value was reached. In the second reactor stage, high final product concentrations
      of up to 220 g L(-1) were reached while the culture was irreversibly product
      inhibited. The experimentally observed changes of the physiological state of the
      culture due to product inhibition were taken into account by introducing a
      segregation into the mathematical model. It was shown that the state of the cells
      was dependent on the current environment and on the previous history. This
      phenomenon was considered in the model by utilizing delay time equations for the
      specific rates of growth on the primary and the secondary substrate. A comparison
      with reproducible measurements gave a good correlation between computation and
      experiment. The mathematical model was validated using independent own
      experimental data. A comparison with a stationary and nonsegregated model
      demonstrated the essential improvements of the novel model. It was deduced from
      the model calculations that high product formation rates of 3.3-3.5 g L(-1) h(-1)
      as well as high final DHA concentrations of 196-215 g L(-1) can be obtained with
      a residual broth volume in the first reactor stage of 2% and a DHA threshold
      value in the range of 100-110 g L(-1).

PMID- 16454521
TI  - Polymer-templated microarrays for highly reliable plaque purification.
AB  - To infect cells with a particular multiplicity of infection, it is essential to
      know the concentration of virus in the inoculum. Here we describe a highly
      reliable and controllable method for plaque purification using cell-repellent
      surfaces micropatterned on the substrate. Micropatterning of localized chemical
      or biochemical domains has the potential to become a powerful tool in controlling
      the seeding of cells. The cell array was reliably fabricated with micropatterned
      surfaces, and the number of cells in a pattern was easily controlled by the cell
      density in the media and micropattern size. The cell micropatterns were infected
      with baculoviruses to form an array of virus plaques. GFP-modified and wild-type
      baculoviruses were used to verify the feasibility of purifying a specific plaque.
      Using confocal microscopy, GFP-expressing plaques were readily selectable and
      removable.

PMID- 16454522
TI  - Exploitation of the adsorptive properties of depth filters for host cell protein
      removal during monoclonal antibody purification.
AB  - Depth filtration has been widely used during process scale clarification of cell
      culture supernatants for the removal of cells and cell debris. However, in
      addition to their filtration capabilities, depth filters also possess the ability
      to adsorb soluble species. This aspect of depth filtration has largely not been
      exploited in process scale separations and is usually ignored during cell culture
      harvest development. Here, we report on the ability of depth filters to
      adsorptively remove host cell protein contaminants from a recombinant monoclonal
      antibody process stream and characterize some of the underlying interactions
      behind the binding phenomenon. Following centrifugation, filtration through a
      depth filter prior to Protein A chromatographic capture was shown to
      significantly reduce the level of turbidity observed in the Protein A column
      eluate of the monoclonal antibody. The Protein A eluate turbidity was shown to be
      linked to host cell protein contaminant levels in the Protein A column load and
      not to the DNA content. Analogous to flowthrough chromatography in which
      residence time/bed height and column loading are key parameters, both the number
      of passes through the depth filter and the amount of centrifuge centrate loaded
      on the filter were seen to be important operational parameters governing the
      adsorptive removal of host cell protein contaminants. Adsorption of proteins to
      the depth filter was shown to be due to a combination of electrostatic and
      hydrophobic adsorptive interactions. These results demonstrate the ability to
      employ depth filtration as an integrative unit operation combining filtration for
      particulate removal with adsorptive binding for contaminant removal.

PMID- 16454523
TI  - Fabrication of hyaluronic acid hydrogel beads for cell encapsulation.
AB  - Hyaluronic acid (HA) hydrogel beads were prepared by photopolymerization of
      methacrylated HA and N-vinylpyrrolidone using alginate as a temporal spherical
      mold. Various fabrication conditions for preparing the hydrogel beads, such as
      the concentration of methacrylated HA and UV irradiation time, were optimized to
      control swelling properties and enzymatic degradability. A new concept for cell
      encapsulation is proposed in this paper. Viable cells were directly injected into
      the hydrogel beads using a microinjection technique. When bovine articular
      chondrocytes were injected into HA hydrogel beads and cultivated for 1 week, the
      cells could proliferate well within the HA beads. HA hydrogel beads could be
      potentially used as injectable cell delivery vehicles for regenerating tissue
      defects.

PMID- 16454524
TI  - Nucleation and growth of microtubules from gamma-tubulin-functionalized gold
      surfaces.
AB  - Microtubules are protein filaments that are emerging as potential building blocks
      in manufacturing nanoscale structures and systems such as interconnecting
      nanowires. Future development in using microtubules necessitates a control of
      their nucleation and growth. We report the controlled nucleation and growth of
      microtubules from functionalized gold on a hydrophilic oxidized silicon wafer.
      The gold substrate is functionalized with gamma-tubulin, a natural nucleating
      agent for microtubule growth. We show that the attached gamma-tubulin retains its
      biological functionality and leads to nucleation and assembly of microtubules
      from the functionalized gold surface. We also analyze the interplay between the
      geometry of the nucleating substrates and the morphology of microtubules arrays
      and networks grown from them. We consider two geometrical arrangements of the
      substrates: (a) a square lattice of small gold pads on a hydrophilic oxidized
      silicon wafer and (b) a large flat surface. Fluorescence microscopy and scanning
      electron microscopy are employed to provide a detailed characterization of the
      length and morphology of the nucleated and grown microtubules. The observed
      microtubule morphologies are modeled, analyzed and discussed within the context
      of reaction-diffusion and nucleation controlled processes.

PMID- 16454525
TI  - Regulation of recombinant monoclonal antibody production in chinese hamster ovary
      cells: a comparative study of gene copy number, mRNA level, and protein
      expression.
AB  - We performed a comparative analysis on CHO cells with varying recombinant
      monoclonal antibody production rates (qAb) and investigated the regulation of MAb
      production. Two families of CHO cells each composed of one parental and two
      progeny cell lines, generated by stepwise increases in methotrexate (MTX)
      concentration, were studied. The MAb heavy chain (HC) and light (LC) gene copy
      numbers and mRNA levels were quantitated by Southern and northern blotting in
      midexponential growth phase. We observed 2- to 3-fold amplification in gene copy
      numbers in high producing cell lines when compared with parental cell lines.
      However, the mRNA levels in the high producers were 5- to 7-fold higher,
      correlating well with the 5- to 7-fold increase in qAb. These results were
      confirmed by real-time qPCR analysis. Our study reveals that the MTX-mediated MAb
      overexpression results from both an increase in the gene copy number and more
      efficient transcription of each gene copy. We also observed that the HC to LC
      gene copy ratio may affect the protein yield in MAb expression systems.

PMID- 16454526
TI  - Stability of serum-free and purified baculovirus stocks under various storage
      conditions.
AB  - In a context of large-scale production of baculoviruses in serum-free media for
      use as gene delivery vectors, the stability of these viruses has become an
      important factor. The development of robust processes heavily relies on
      baculovirus stock stability. In the present work, we studied over a period of 300
      days the stability of baculovirus vectors produced in serum-free media stored at
      4, -20, or -80 degrees C or in liquid nitrogen. The viral stocks investigated
      were either crude baculovirus supernatant, baculovirus supernatant concentrated
      10 times and diafiltered against fresh serum-free media by tangential flow
      filtration, or baculovirus purified by size exclusion chromatography. The results
      showed that baculovirus supernatant and diafiltered concentrate stored at 4
      degrees C underwent a progressive loss of infectivity after a period of 100 and
      50 days of storage, respectively. Aggregation has been recognized as the probable
      mechanism for the loss of infectivity. Baculovirus stocks were unstable at -20
      degrees C, whereas in liquid nitrogen they retained infectivity after successive
      freeze thaw cycles. Concentration and diafiltration of baculovirus supernatant
      prior to storing at -80 degrees C contributed to improving viral stock stability
      over time. Glycerol as well as DMSO and sucrose have proven to be equally
      effective as additives to maintain the purified baculovirus stability after
      storage at -80 degrees C or in liquid nitrogen.

PMID- 16454527
TI  - Beta-galactosidase catalyzed selective galactosylation of aromatic compounds.
AB  - A new approach to galacto-oligosaccharides and galacto-conjugates synthesis
      performed by the beta-galactosidase from Kluyveromyces lactis is reported. The
      enzymatic galactosylation of eight kinds of adsorbed aromatic primary alcohols,
      in particular the two drugs guaifenesin and chlorphenesin, gave the corresponding
      beta-D-galacto-pyranosides in yields ranging between approximately 10% and 96%.
      For the first time, we have showed that the adsorption of acceptor substrates
      onto solid supports such as silica gel influences the yield and the selectivity
      of galacto-conjugates synthesis. In particular, we observed that adsorption of
      acceptor favored the synthesis of digalactosylated compounds.

PMID- 16454528
TI  - Novel chemically synthesized salicylate derivative as an effective elicitor for
      inducing the biosynthesis of plant secondary metabolites.
AB  - Trifluoroethyl salicylate (TFESA), a novel salicylate derivative, was chemically
      synthesized and evaluated by bioassay as a potential elicitor for inducing the
      biosynthesis of plant secondary metabolites. A cell line of Taxus chinensis,
      which stably produced a high level of bioactive taxuyunnanine C (Tc), was taken
      as a model plant cell system. The application of TFESA to the cell cultures could
      significantly induce Tc biosynthesis, although the cell growth was slightly
      inhibited. More interestingly, Tc production was enhanced more in the presence of
      TFESA compared with a structure-similar well-known elicitor, salicylic acid (SA).
      For example, addition of 100 microM TFESA on day 7 led to a high Tc content of
      21.9 +/- 0.1 mg g(-1) (at day 21), whereas the Tc content was 14.0 +/- 0.2 and
      16.7 +/- 0.3 mg g(-1) for the control and that with addition of 100 microM SA,
      respectively. The results indicate that the newly synthesized TFESA can act as a
      powerful elicitor for secondary metabolism induction in plant cell cultures.

PMID- 16454529
TI  - Volatile fatty acid-sensing system involving coenzyme-A transferase.
AB  - On-site monitoring of volatile fatty acids (VFAs), such as propionate, is
      industrially and medically important. The present study developed a VFA
      biosensing system comprised of two recombinant enzymes, propionate coenzyme A
      (CoA) transferase (PCT) from Clostridium propionicum and acyl-CoA oxidase from
      Arabidopsis thaliana. This system produced hydrogen peroxide in the presence of
      acetyl-CoA, oxygen, and VFA substrates, which could be quantified by colorimetric
      methods using peroxidase and dye reagents (e.g., p-aminobenzoic acid plus 4
      aminoantipyrine or Amplex Red). The use of PCT and acetyl-CoA, rather than acyl
      CoA synthetases (ACS) and CoA-SH, obviated a background reaction of dye reagents
      with CoA-SH and enabled very sensitive detection of VFAs (down to 1 microM
      propionate, more than 100-fold more sensitive compared to previously developed
      ACS biosensors). We demonstrated its utility by measuring propionate
      concentrations in serum and fermentation samples. Results suggest that our
      biosensing system is applicable to the detection of propionate in medical and
      fermentation samples.

PMID- 16454530
TI  - Enhancement of monascus pigment production by the culture of Monascus sp. J101 at
      low temperature.
AB  - In general, high broth viscosity is a key factor to be considered in a submerged
      fermentation of filamentous fungi. High broth viscosity was also observed in a
      batch fermentation of Monascus sp. J101 at 30 degrees C. In a batch culture at 30
      degrees C, most cell growth was accomplished within 48 h, which induced highly
      entangled clumps. The resultant high viscosity induced heterogeneity inside the
      fermentor, poor oxygen transfer, and low pigment yield. However, these problems
      could be overcome by reducing fungal growth rate through culture at low
      temperature (25 degrees C). Cell growth was moderate and continued for 120 h, and
      low viscosity was maintained. The DO levels remained at 50% or higher with good
      mixing. As a result, the pigment yield at 25 degrees C was 10 times greater than
      at 30 degrees C.

PMID- 16454532
TI  - Advances in understanding drug-induced neuropathies.
AB  - Many commonly used medications have neurotoxic adverse effects; the most common
      of these is peripheral neuropathy. Neuropathy can be a dose-limiting adverse
      effect for many medications used in life-threatening conditions, such as
      malignancy and HIV-related disease. Epidemiological evidence supports previous
      case reports of HMG-CoA reductase inhibitors (or 'statins') causing an axonal
      sensorimotor neuropathy or a purely small-fibre neuropathy in some patients. The
      neuropathy improves when the medication is withdrawn. Despite the association
      between HMG-CoA reductase inhibitors and neuropathy, the risk is low compared
      with the significant vascular protective benefits. Oxaliplatin, a new platinum
      chemotherapy agent designed to have fewer adverse effects than other such agents,
      has been shown to cause a transient initial dysaesthesia in addition to an axonal
      polyneuropathy. Thalidomide, an old therapy currently being utilised for new
      therapeutic indications (e.g. treatment of haematological malignancies), is
      associated with a painful, axonal sensorimotor neuropathy that does not improve
      on withdrawal of the drug. Nucleoside reverse transcriptase inhibitors are
      important components of highly active antiretroviral therapy, but are associated
      with a sensory neuropathy that is likely to be due to a direct effect of these
      drugs on mitochondrial DNA replication. New research demonstrates that lactate
      levels may help discriminate between neuropathy caused by nucleoside analogues
      and HIV-induced neuropathy. Understanding the mechanism of drug-induced
      neuropathy has led to advances in preventing this disabling condition.

PMID- 16454531
TI  - Valproic acid in epilepsy : pregnancy-related issues.
AB  - Valproic acid (sodium valproate) is widely used as a first-line antiepileptic
      agent. As with many antiepileptic drugs, there are a number of consequences
      associated with the use of valproic acid in women of child-bearing potential.
      Most pregnancies have a favourable outcome in women with epilepsy, and these
      women should not be discouraged from becoming pregnant. Unlike many other
      antiepileptic drugs, valproic acid has no significant pharmacokinetic
      interactions with the steroid hormones used in oral contraceptives. During
      pregnancy, the major risks to mother and child result from loss of seizure
      control on the one hand, and an elevated risk of major congenital malformations
      due to antiepileptic drug treatment on the other. In particular, an elevated risk
      of major congenital malformations associated with valproic acid use has been a
      consistent finding in studies of patient registries and several large case
      series. In addition, developmental delay, characterised by low verbal IQ, has
      also been reported in children exposed to valproic acid in utero, although the
      relative risk is not precisely known. For these reasons, pregnancies in women
      being treated with valproic acid need to be planned, and the benefit-risk ratios
      associated with continuing valproic acid or changing treatment need to be
      discussed with the patient. When treatment with valproic acid is the most
      appropriate treatment to achieve optimal seizure control, a number of measures
      can be implemented to minimise risk to the fetus. These include the use of the
      lowest possible effective dose of valproic acid in monotherapy (ideally <1000
      mg/day), appropriate folic acid supplementation and close antenatal monitoring.
      Regular counselling is a prerequisite for informed planning of pregnancies and
      optimisation of the probability of a healthy outcome. Future research on valproic
      acid and pregnancy should involve risk assessment in large, population-based
      prospective studies.

PMID- 16454533
TI  - Botulinum toxin treatment of adult spasticity : a benefit-risk assessment.
AB  - Injections of botulinum toxin have revolutionised the treatment of focal
      spasticity. Before their advent, the medical treatment for focal spasticity
      involved oral anti-spasticity drugs, which had decidedly non-focal adverse
      effects, and phenol injections. Phenol injections could be difficult to perform,
      could cause sensory complications and had effects that were of uncertain duration
      and magnitude. Furthermore, few neurologists knew how to perform them as they
      were mostly the province of rehabilitation specialists. Botulinum toxin can
      produce focal, controllable muscle weakness of predictable duration, without
      sensory adverse effects. Randomised clinical trials (RCTs) involving patients
      with spasticity resulting from a variety of diseases (mainly stroke and multiple
      sclerosis) have clearly shown that botulinum toxin type A (Dysport and Botox) can
      temporarily (for approximately 3 months) reduce spastic hypertonia in the elbow,
      wrist and finger flexors of the upper limbs, and the hip adductors and ankle
      plantar flexors in the lower limbs. The clinical benefits from this reduction of
      neurological impairment are best shown in the upper limb, with less disability of
      passive function and reduced caregiver burden. In the lower limbs, there is
      improved perineal hygiene from hip adductor injections. The benefits of reducing
      ankle plantar flexor tone are less well established. Pain is also reduced,
      possibly by mechanisms other than muscle weakness. Improved active function has
      not yet been clearly demonstrated in RCTs, only in open-label trials. The safety
      of botulinum toxin-A is impressive, with minimal (mainly local) adverse effects.
      There are little data on the use of botulinum toxin type B (Myobloc or Neurobloc)
      in spasticity and the only RCT that has examined this did not show tone
      reduction; dry mouth appeared to be a very common adverse effect. There are also
      very little data to allow a benefit-risk comparison of phenol and botulinum toxin
      injections; each have their clinical and technical advantages and disadvantages,
      and phenol is much less costly than botulinum toxin.

PMID- 16454534
TI  - Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved
      tolerability?
AB  - Psoriasis is a chronic inflammatory disease of the skin affecting approximately
      2% of the world's population. Traditional systemic treatments, including
      methotrexate, ciclosporin, psoralen plus UVA (PUVA), oral retinoids and fumaric
      acid esters, are widely used for severe disease and are effective in the short
      term. Severe psoriasis is a chronic disease and patients and physicians have
      expressed concerns about possible harm from organ toxicity, such as skin cancer
      (PUVA), hyperlipidaemia (retinoids), renal (ciclosporin) or hepatotoxicity
      (methotrexate). Long-term monitoring is required and may not detect early organ
      damage. The pathophysiology of psoriasis remains to be clarified, but advances
      toward the understanding of the immunological basis of psoriasis have uncovered
      the involvement of immunological pathways; for example, the role of tumour
      necrosis factor (TNF)-alpha, T cell proliferation and T cell activation, and
      migration to the epidermis. This advancement in knowledge combined with
      developments in recombinant technologies has led to the development of target
      specific therapies. Biological agents are defined as proteins that can be
      extracted from animal tissue or produced via recombinant DNA technologies and
      possess pharmacological activity. Adalimumab, alefacept, infliximab, efalizumab
      and etanercept are examples of biological agents currently used for the treatment
      of psoriasis. Some of these are also therapy for other autoimmune conditions,
      such as rheumatoid arthritis and Crohn's disease. These biological agents are
      effective in psoriasis but raise new safety concerns. Information on the safety
      of biological agents in conditions such as rheumatoid arthritis and Crohn's
      disease can not be directly extrapolated to psoriasis. An increased incidence of
      lymphomas has been postulated to be associated with etanercept, infliximab and
      adalimumab; serious infections, such as tuberculosis, have also been reported
      with these three biologicals, all of which target TNF-alpha. Demyelinating
      disorders, such as multiple sclerosis, have been reported with some biologicals
      as has congestive heart failure. Alefacept, because of its mechanism of action of
      lowering the number of active T cells, is associated with low T cell counts.
      Efalizumab has been associated with thrombocytopenia and haemolytic anaemia. Data
      on the safety of >2.5 years' continuous treatment with efalizumab are reassuring
      and a valuable beginning to understanding the role and risk of harm of long-term
      therapy for a chronic disease. Longer follow-up studies and safety databases, for
      each of the biologicals used in psoriasis, are needed to ensure both prolonged
      efficacy and minimal risk of harm.

PMID- 16454535
TI  - Short-term chloral hydrate administration and cancer in humans.
AB  - OBJECTIVE: Chloral hydrate, used as a hypnosedative in adults and children, has
      been shown to be genotoxic and carcinogenic in animal studies. We investigated
      the potential causal association between chloral hydrate exposure and cancer risk
      in humans. METHODS: Cancer incidence was previously determined via biennial
      screening analyses of the 215 most commonly used drugs between 1976 and 1998 for
      a cohort of 143,574 outpatients at Kaiser Permanente who had prescriptions filled
      between 1969 and 1973. Among users of chloral hydrate, statistically significant
      elevations in standardised morbidity ratios were observed during various years
      for cancer at five anatomical sites, including the lung, stomach, prostate, skin
      melanoma and mouth floor. In this analysis, these associations were investigated
      using: (i) a dose-response analysis among exposed subjects; and (ii) a two-stage
      design with exposed and non-exposed persons. RESULTS: There was evidence of an
      increasing risk of prostate cancer with increasing number of dispensings of
      chloral hydrate, which persisted after controlling for benign prostatic
      hypertrophy, vasectomy and obesity; however, the trend was not statistically
      significant. There was no evidence of a dose-response relationship between
      chloral hydrate and risk of any of the other four cancers. In the two-stage
      design, analyses comparing exposed and unexposed subjects showed no increased
      risk of cancer after controlling for confounding variables; however, the data
      were suggestive for prostate cancer, where the increased risk associated with
      chloral hydrate exposure after adjustment for confounding variables persisted. No
      dose-response relationship was seen for any of the other four cancer sites.
      CONCLUSIONS: To our knowledge, this is the first study to examine the
      relationship between chloral hydrate exposure and cancer risk in humans. There
      was no persuasive evidence to support a causal relationship between chloral
      hydrate exposure in humans and the development of cancer. However, statistical
      power was low for weak associations, particularly for some of the individual
      cancer sites. Although animal data using much higher doses of chloral hydrate
      have demonstrated its genotoxicity and carcinogenicity, the effects of chloral
      hydrate in humans are still uncertain.

PMID- 16454536
TI  - The prevalence of potential drug-drug interactions in patients with heart failure
      at hospital discharge.
AB  - BACKGROUND/OBJECTIVE: Pharmacotherapy for heart failure is complex and, due to
      polypharmacy, is associated with a large risk of potential drug-drug interactions
      (DDIs). The objective of the present study was to assess the prevalence of
      potential DDIs in the medication of hospitalised heart failure patients and to
      evaluate their clinical relevance. STUDY DESIGN/METHODS: The medication of 400
      patients was retrospectively analysed for potential DDIs at hospital admission
      and discharge using a computerised drug interaction program. Main inclusion
      criteria were the diagnosis of heart failure and a minimum of two drug
      prescriptions at discharge. RESULTS: In the study population of 400 heart failure
      patients (median age 79 years, 55.5% men), the median number of drugs per patient
      was lower at admission than at discharge (6 [interquartile range {IQR} 4-9] vs 8
      [IQR 6-10]; p < 0.001). At hospital admission, a total of 863 potential DDIs were
      detected in 272 patients (68.0%; 95% CI 63.4, 72.6). At discharge, 1171 potential
      DDIs were detected in 355 patients (88.8%; 95% CI 85.7, 91.8). This corresponds
      with a significant increase in the median number of potential DDIs per patient
      from admission to discharge (1.5 [IQR 0-3] vs 3 [IQR 1-4]; p < 0.001). Of the
      1171 potential DDIs at discharge, 432 (36.9%) were prevalent at admission and 739
      (63.1%) resulted from a medication change during the hospital stay. Of these 739
      new potential DDIs, the severity of the potential adverse effect was rated as
      'major' in 190 (25.7%) patients, 'moderate' in 482 (65.2%) and 'minor' in 67
      (9.1%). The 190 potential DDIs with major severity were recorded in a total of
      145 patients (36.3%; 95% CI 31.5, 41.0%). Hyperkalaemia was the most prevalent
      potential adverse effect of major severity (n = 93) and the combination of an ACE
      inhibitor with a potassium-sparing diuretic was recorded in 64 (16.0%) patients.
      CONCLUSIONS: The study shows that hospitalisation of patients with heart failure
      results in an increase in the number of drugs prescribed per patient and,
      thereby, also in the number of potentially interacting drug combinations per
      patient. Although electronic drug interaction programs are a valuable tool to
      check for potential DDIs, the clinical relevance of most potential DDIs can only
      be judged by assessment of the individual patient.

PMID- 16454537
TI  - The Erice declaration : the critical role of communication in drug safety.
AB  - The Erice Declaration on Communicating Drug Safety Information, first published
      in September 1997, provides a vision of vigorous, open, ethical, patient-centred
      communications in drug safety that the world has yet to achieve. The Declaration
      is reprinted here as a further stimulus to all parties to renew their commitment
      and to add new momentum to the improvements which have undoubtedly taken place in
      the past few years. The content of the Declaration is briefly reviewed, and some
      of the continuing communications challenges and problems are outlined.

PMID- 16454540
TI  - Current understanding of contrast media reactions and implications for clinical
      management.
AB  - Iodinated contrast media (CM) are an integral part of modern diagnostic medicine.
      Although these agents are considered to be relatively safe, adverse effects in
      the form of allergy-like reactions occur in a significant number of exposed
      patients. These reactions may be divided into immediate and delayed responses.
      Immediate (within 1 hour of administration) anaphylactic reactions range from
      urticaria and angioedema to laryngeal oedema, hypotension and even death. Delayed
      reactions to CM occur from 1 hour to 1 week after administration and usually have
      mostly cutaneous manifestations. History of prior CM reactions and atopy
      predispose patients to CM reactions. Despite intense research into the
      pathogenesis of the immediate anaphylactoid responses, new evidence shows that
      true IgE type I hypersensitivity mediation occurs only in rare, severe cases. The
      aetiology appears to be multifactorial in most individuals. There is strong
      evidence to conclude that type IV hypersensitivity is responsible for the delayed
      reactions to CM. Although switching to non-ionic agents significantly reduces the
      incidence of immediate reactions to CM, there is little consensus regarding
      corticosteroid prophylaxis in high-risk individuals. Skin testing and provocative
      challenges also provide little security. Therefore, physicians must be better
      prepared to treat immediate anaphylactoid responses. Preventing delayed CM
      reactions is best performed with patch and delayed intradermal testing in those
      with a history of prior reactions, although false-negative results have been
      reported. Corticosteroids and antihistamines may be required for treatment. Until
      newer agents are developed that negate these issues, healthcare providers must
      strive to better understand the risk factors associated with CM reactions, as
      well as the available prophylactic and treatment options.

PMID- 16454541
TI  - HMG CoA reductase inhibitors and impotence: two case series from the Spanish and
      French drug monitoring systems.
AB  - OBJECTIVE: HMG CoA Reductase inhibitors, more commonly called statins, are used
      in the pharmacological management of hyperlipidaemia. At present, the use of
      these drugs is increasing worldwide. They have been linked to certain adverse
      drug reactions, including impotence. The aim of the present study is to explore
      the basis of the association between statin use and impotence using data from
      spontaneous reports. METHOD: We analysed the cases of impotence associated with
      statins that were collected by the Spanish and French pharmacovigilance systems.
      We used cases of impotence as a numerator and consumption data as a denominator
      to estimate the cumulative reported incidence of impotence. RESULTS: Thirty-eight
      cases of impotence associated with statins have been identified in the database
      of the Spanish pharmacovigilance system; overall, there was a temporal sequence
      of events in all cases and the adverse reaction disappeared after drug withdrawal
      in 93% of the cases. Sixteen patients had also been treated with other drugs. In
      France, 37 cases were collected. In 85% of these cases recovery from the adverse
      reaction was observed after drug withdrawal; there was a positive rechallenge in
      five cases, and 15 patients were receiving other drugs at the same time. No
      significant differences among reported incidences with different statins were
      found. CONCLUSION: Considering the widespread use of this drug class and the
      under-reporting of this particular reaction it could affect a large number of
      patients. The reaction seems to be reversible in most of the cases after drug
      withdrawal. Doctors should be aware of this potential adverse reaction when
      prescribing statins to their patients.

PMID- 16454538
TI  - Interactions between antiepileptic and antipsychotic drugs.
AB  - Antiepileptic and antipsychotic drugs are often prescribed together. Interactions
      between the drugs may affect both efficacy and toxicity. This is a review of
      human clinical data on the interactions between the antiepileptic drugs
      carbamazepine, valproic acid (sodium valproate), vigabatrin, lamotrigine,
      gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin,
      felbamate, zonisamide, phenobarbital and phenytoin with the antipsychotic drugs
      risperidone, olanzapine, quetiapine, clozapine, amisulpride, sulpiride,
      ziprasidone, aripiprazole, haloperidol and chlorpromazine; the limited
      information on interactions between antiepileptic drugs and zuclopenthixol,
      periciazine, fluphenazine, flupenthixol and pimozide is also presented. Many of
      the interactions depend on the induction or inhibition of the cytochrome P450
      isoenzymes, but other important mechanisms involve the uridine diphosphate
      glucuronosyltransferase isoenzymes and protein binding. There is some evidence
      for the following effects. Carbamazepine decreases the plasma concentrations of
      both risperidone and its active metabolite. It also decreases concentrations of
      olanzapine, clozapine, ziprasidone, haloperidol, zuclopenthixol, flupenthixol and
      probably chlorpromazine and fluphenazine. Quetiapine increases the ratio of
      carbamazepine epoxide to carbamazepine and this may lead to toxicity. The data on
      valproic acid are conflicting; it may either increase or decrease clozapine
      concentrations, and it appears to decrease aripiprazole concentrations.
      Chlorpromazine possibly increases valproic acid concentrations. Lamotrigine
      possibly increases clozapine concentrations. Phenobarbital decreases clozapine,
      haloperidol and chlorpromazine concentrations. Phenytoin decreases quetiapine,
      clozapine, haloperidol and possibly chlorpromazine concentrations. There are
      major gaps in the data. In many cases there are no published clinical data on
      interactions that would be predicted on theoretical grounds.

PMID- 16454539
TI  - NSAID-associated adverse effects and acid control aids to prevent them: a review
      of current treatment options.
AB  - NSAIDs are central to the clinical management of a wide range of conditions.
      However, NSAIDs in combination with gastric acid, which has been shown to play a
      central role in upper gastrointestinal (GI) events, can damage the gastroduodenal
      mucosa and result in dyspeptic symptoms and peptic lesions such as
      ulceration.NSAID-associated GI mucosal injury is an important clinical problem.
      Gastroduodenal ulcers or ulcer complications occur in up to 25% of patients
      receiving NSAIDs. However, these toxicities are often not preceded by indicative
      symptoms. Data obtained from the Arthritis, Rheumatism, and Aging Medical
      Information System have shown that 50-60% of NSAID-associated peptic ulcer cases
      can remain clinically silent and do not present until complications occur.
      Therefore, prophylactic treatment to prevent GI complications may be necessary in
      a substantial proportion of NSAID users, especially those in groups associated
      with a high risk of developing these complications. Use of cyclo-oxygenase (COX)
      2 selective NSAIDs, also known as 'coxibs', substantially reduces the incidence
      of upper GI toxicities seen with non-selective NSAIDs. However, there are
      concerns regarding the cardiovascular safety of coxibs. For this reason, the US
      FDA recommends minimal use of coxibs and only when strictly necessary.
      Additionally, rofecoxib has been removed from the US market and sales of
      valdecoxib have been suspended. Furthermore, upper GI toxicities still occur in
      patients receiving coxibs. Therefore, cotherapies are required to prevent and/or
      heal upper GI effects associated with NSAID use. Effective prophylactic and
      treatment strategies include misoprostol, histamine H(2) receptor antagonists and
      proton pump inhibitors (PPIs). The key role that gastric acid plays in upper GI
      adverse events among NSAID users suggests that it is important to choose the most
      effective agent for acid control to alleviate symptoms, heal mucosal erosions and
      improve the reduced quality of life in this patient population. PPIs provide
      effective acid suppression, which is essential to avoid GI mucosal injury, and
      they are, therefore, capable of dramatically decreasing the morbidity and
      mortality associated with this disorder. Since many serious GI complications are
      not heralded by any previous symptoms, physicians need to be aware of risk factor
      profiles that predispose patients to serious GI problems. Physicians also need to
      initiate the appropriate preventative acid suppressive therapy to minimise the
      burden of NSAID-associated GI adverse effects.

PMID- 16454542
TI  - Ophthalmological events in patients receiving risedronate: summary of information
      gained through follow-up in a prescription-event monitoring study in England.
AB  - BACKGROUND: In the UK, the nitrogen bisphosphonate risedronate is licensed for
      the prevention and treatment of osteoporosis and corticosteroid-induced
      osteoporosis in postmenopausal women. It is also licensed for the treatment of
      Paget's disease. During a prescription-event monitoring (PEM) study on
      risedronate we noted a number of ophthalmological events. Recently, case reports
      of ophthalmological adverse drug reactions in patients taking bisphosphonates
      were published in the medical literature. The aim of this study was to further
      evaluate the association of ophthalmological events reported in relation to
      risedronate treatment during a PEM study on the drug. METHODS: An observational
      cohort study (PEM study) was conducted in England between September 2000 and June
      2002. General practitioners (GPs) were asked for follow-up information on
      selected events. Events followed up were classified as either 'probably',
      'possibly' or 'unlikely' to be related to risedronate, using a modified WHO
      classification. If insufficient information was obtained on the follow-up
      questionnaire, the cases were categorised as 'unassessable'. RESULTS: Of the
      total PEM study cohort of 13 643 patients, 11 156 (82%) were females and 2398
      (18%) were males. We received 359 reports of ophthalmological events in 313
      patients during the entire study period. Of these we followed up 178 events in
      178 patients. Nineteen events in 19 patients were assessed as possibly or
      probably related to risedronate. The age range for these patients was 50-92 years
      and the time to onset ranged from 7 days to 5 months. Dry eye (six reports), sore
      eye (five reports) and conjunctivitis (three reports) were the most frequently
      reported ophthalmological events assessed as probably or possibly related to
      risedronate therapy. GPs also reported several other inflammatory conditions of
      the eye, amongst them two events each of iritis and episcleritis as well as one
      of keratitis. However, the information received on follow up of these events was
      insufficient to make causality assessments. CONCLUSION: Patients receiving
      risedronate can present with a variety of signs and symptoms affecting the eye
      with different degrees of severity. Patients may present after the first month of
      treatment. Doctors should have an increased awareness of possible
      ophthalmological adverse drug reactions in patients receiving this drug, which
      may affect the eyesight in a population at increased risk of fracture if they
      fall.

PMID- 16454543
TI  - Adverse drug reaction-related hospitalisations: a nationwide study in The
      Netherlands.
AB  - BACKGROUND: The incidence of adverse drug reaction (ADR)-related hospitalisations
      has usually been assessed within hospitals. Because of the variability in results
      and methodology, it is difficult to extrapolate these results to a national
      level. OBJECTIVES: To evaluate the incidence and characteristics of ADR-related
      hospitalisations in The Netherlands in 2001. METHODS: We conducted a nationwide
      study of all hospital admissions in 2001. Data were retrieved from a nationwide
      computer database for hospital discharge records. All acute, non-planned
      admissions to all Dutch academic and general hospitals in 2001 were included in
      the study (n = 668 714). From these admissions we selected all hospitalisations
      that were coded as drug-related, but intended forms of overdose, errors in
      administration and therapeutic failures were excluded. Hence, we extracted all
      ADR-related hospitalisations. We compared age, sex and the risk of a fatal
      outcome between patients admitted with ADRs and patients admitted for other
      reasons, as well as the most frequent main diagnoses in ADR-related
      hospitalisations and which drugs most frequently caused the ADRs. In addition, we
      evaluated to what extent these ADRs were reported to the Netherlands
      Pharmacovigilance Centre Lareb for spontaneous ADR reporting. RESULTS: In 2001,
      12 249 hospitalisations were coded as ADR related. This was 1.83% of all acute
      hospital admissions in The Netherlands (95% CI 1.80, 1.86). The proportion
      increased with age from 0.8% (95% CI 0.75, 0.85) in the <18 years group to 3.2%
      in the >/=80 years group (95% CI 3.08, 3.32). The most frequent ADR-related
      diagnoses of hospitalisations were bleeding (n = 1048), non-specified 'unintended
      effect of drug' (n = 438), hypoglycaemia (n = 375) and fever (n = 347). The drugs
      most commonly associated with ADR-related hospitalisations were anticoagulants (n
      = 2185), cytostatics and immunosuppressives (n = 1809) and diuretics (n = 979).
      Six percent of the ADR-related hospitalisations had a fatal outcome (n = 734).
      Older age and female gender were associated with ADR-related hospitalisations.
      Only approximately 1% of the coded ADRs causing hospitalisation were reported to
      our national centre for spontaneous ADR reporting. CONCLUSION: The proportion of
      ADR-related hospitalisations is substantial, especially considering the fact that
      not all ADRs may be recognised or mentioned in discharge letters. Under-reporting
      of ADRs that result in hospital admission to our national centre for spontaneous
      ADR reporting was considerable.

PMID- 16454544
TI  - The effect of detection approaches on the reported incidence of tenfold errors.
AB  - BACKGROUND: Tenfold errors in calculation of paediatric drug doses are often life
      threatening. The magnitude and characteristics of this phenomenon have not been
      fully described. OBJECTIVES: The objective of this study was to describe the
      incidence and nature of paediatric tenfold errors and to describe the effect of
      different detection approaches on the detection of such errors. METHODS: To
      evaluate the incidence of tenfold errors, data were collected from three
      different studies on medication errors all conducted at a large tertiary care
      paediatric hospital: (i) a study investigating medication event reports to the
      hospital's Medication Incident Committee; (ii) a study auditing the charts of
      1532 patients in the emergency department (ED) and; (iii) a prospective study of
      medication errors occurring during mock code resuscitations in the ED. RESULTS:
      In the first study, 20 tenfold errors were reported during the surveyed period.
      Almost all errors were prescribing errors. The calculated incidence was 1 per 22
      500 doses prescribed. In chart auditing study in the ED, two tenfold errors where
      found in 1678 orders. In the prospective study, four tenfold errors were
      identified in eight mock resuscitations (125 orders for drugs). CONCLUSION: The
      incidence of tenfold errors in paediatrics varies dramatically when different
      detection approaches are used. The rate of tenfold errors may be especially high
      in resuscitation situations and is underestimated by spontaneous reporting.

PMID- 16454545
TI  - An assessment of the publicly disseminated evidence of safety used in decisions
      to withdraw medicinal products from the UK and US markets.
AB  - BACKGROUND: The objective of this study was to assess the publicly disseminated
      evidence used to support decisions to withdraw medicinal products for safety
      reasons, and related implications for the conduct of systematic reviews of harm.
      METHODS: Medicinal products withdrawn from the UK and US markets for safety
      reasons were identified from websites of the UK Medicines Control Agency (now
      known as the Medicines and Healthcare products Regulatory Agency) and the US FDA.
      Related scientific evidence was identified from communications made to the public
      and healthcare professionals at the time of each product withdrawal. Evidence for
      each product withdrawal decision was classified according to study design and
      outcome. RESULTS: Eleven products were withdrawn during 1999-2001. Randomised
      trial evidence was cited for two products (18%) and comparative observational
      studies for two products (18%). Evidence from spontaneous reports supported the
      withdrawal of eight products (73%), with four products (36%) apparently withdrawn
      on the basis of spontaneous reports alone. Only two products (18%) were withdrawn
      on evidence for a patient relevant outcome from comparative studies. CONCLUSIONS:
      It is rare that evidence other than spontaneous reports is cited in support of
      drug withdrawals. The serious implications of product withdrawal mandate the
      elevation of the level of evidence that supports such public health decisions.
      Once suspicions of important safety hazards have emerged, prospective studies may
      be unfeasible and may be seen as unethical. Prospective studies can strengthen
      the evidence base and should be planned to commence when every drug is first
      marketed. Systematic reviews are unlikely to elicit evidence of harm associated
      with a drug unless they include spontaneous reports and surrogate outcomes.

PMID- 16454546
TI  - Significance of field validation in the interlaboratory comparison program in
      cervicovaginal cytology.

PMID- 16454548
TI  - A procedure for rapid issue of red cells for emergency use.

PMID- 16454550
TI  - Subcutaneous phaeohyphomycosis caused by Cladophialophora bantiana.

PMID- 16454551
TI  - Occupational injuries in a pathology residency program.

PMID- 16454552
TI  - Interobserver agreement on microfollicles in thyroid fine-needle aspirates.
AB  - CONTEXT: Although microfollicles are a well-known feature of follicular neoplasms
      in fine-needle aspirates of the thyroid, the level of agreement about classifying
      groups as microfollicles is not known. OBJECTIVE: To determine what features are
      present in groups that are consistently classified as microfollicles. DESIGN: We
      showed 45 small groups of follicular cells each composed of fewer than 50 cells
      from fine-needle aspirates of the thyroid to 12 members of the College of
      American Pathologists Cytopathology Committee, who then classified the groups
      into microfollicles, macrofollicles, and indeterminate groups. RESULTS: Twenty
      groups were consistently classified as microfollicles, 7 groups as
      macrofollicles, and 18 groups as indeterminate. Cases that were consistently
      classified as microfollicles were composed of fewer than 15 cells (19/20 cases),
      were arranged in a circle with a lumen (13/20 cases) that was at least two-thirds
      complete (12/20 cases), and were flat (18/20 cases). Cases that were classified
      as macrofollicular had between 8 and 35 cells, were arranged in sheets composed
      of at least 15 cells (5/7 cases) or rows of 8 cells (2/7 cases), and were flat
      (7/7 cases). In contrast, cases that were indeterminate were composed of either 3
      dimensional groups (5/18 cases), flat groups of fewer than 10 cells (11/18
      cases), or single cells (1/18 cases). CONCLUSION: Not all small groups of
      follicular cells are consistently classified as microfollicles, and some are more
      often classified as macrofollicles. The criteria described here for reproducible
      microfollicles (<15 cells, arranged in a circle that is at least two-thirds
      complete, and flat) may help improve the agreement in classification of
      microfollicles and lead to more consistent classification of thyroid fine-needle
      aspirates.

PMID- 16454553
TI  - Immunoreactivity of MIC2 (CD99) and terminal deoxynucleotidyl transferase in bone
      marrow clot and core specimens of acute myeloid leukemias and myelodysplastic
      syndromes.
AB  - CONTEXT: MIC2 ("thymus leukemia") antigen has been shown to be expressed by T
      cells and monocytes, as well as B cells and granulocyte-lineage cells. It is most
      intensely expressed by the most immature thymus T-lineage cells and is more
      intensely expressed by CD34-positive/CD33-positive myeloid cells (compared to
      more mature myeloid cells) and the earliest CD34-positive/CD10-positive B-cell
      precursor cells (compared to cells of later B-cell precursor stages). CD99 (MIC2)
      is characteristically expressed in precursor B- and T-cell lymphoblastic
      lymphomas/leukemias, as well as in Ewing sarcoma/primitive neuroectodermal tumors
      (ES/PNET). It has also been shown to be expressed in a few terminal
      deoxynucleotidyl transferase (TdT)-positive myeloid processes, but has been
      uniformly negative in TdT-negative myeloid processes. A more recent study showed
      that 43% of acute myeloid leukemias (AMLs) and 55% of chloromas express CD99,
      concluding that CD99 is commonly expressed in AML and rarely seen in
      myeloproliferative disorders, myelodysplastic syndromes, or normal bone marrow.
      Although this study speculated that MIC2 expression was probably not limited to
      TdT-positive AML, there was no comparison with TdT reactivity in this study.
      OBJECTIVE: Since AML and high-grade myelodysplastic syndrome may occasionally be
      difficult to distinguish morphologically from acute lymphoblastic leukemia and
      ES/ PNET, we undertook a study to analyze MIC2 expression in conjunction with TdT
      reactivity in distinguishing AML or high-grade myelodysplastic syndrome from
      acute lymphoblastic leukemia and ES/PNET. DESIGN: We studied bone marrow core and
      clot paraffin specimens from AML (classified according to criteria of the World
      Health Organization; n = 49), myelodysplastic syndromes (n = 4), precursor B-cell
      acute lymphoblastic leukemia (n = 4), ES/PNET (n = 1), and normal bone marrow (n
      = 3) with MIC2 (CD99) and TdT immunohistochemistry. RESULTS: Overall, CD99 was
      expressed in 24 (49%) of 49 AML cases, including all (11/11) TdT-positive cases.
      CD99 was expressed in all subtypes of AML except M5. Myelodysplastic syndromes
      and normal bone marrow specimens were uniformly CD99 negative. Expression of TdT
      was limited to a subset of AML-M0, -M1, -M2, and -M4, and AML with multilineage
      dysplasia. CONCLUSIONS: In contrast to a previous study, CD99 expression was not
      restricted to TdT-positive hematologic proliferations. In particular, the CD99
      positive M3 and M7 AMLs were TdT negative. An M5 AML may likely be excluded based
      on a uniform TdT-negative/CD99-negative immunophenotype. In addition, in our
      experience, CD99 should be routinely evaluated on bone marrow clots, owing to
      decreased reactivity or loss of reactivity in rapid decalcifying (RDO) solution
      decalcified specimens.

PMID- 16454554
TI  - Decreased fragile histidine triad gene protein expression is associated with
      worse prognosis in oral squamous carcinoma.
AB  - CONTEXT: Fragile histidine triad (FHIT) gene is thought to be a tumor suppressor;
      abnormalities in expression have been reported in a variety of neoplasms.
      OBJECTIVE: To determine whether abnormalities of FHIT protein expression or loss
      of heterozygosity in the FHIT gene were correlated with survival or other
      clinical parameters in patients with oral cavity squamous cell carcinoma. DESIGN:
      Fifty-three patients with initial surgical treatment of oral cavity squamous cell
      carcinoma were followed a minimum of 5 years or until death. The FHIT protein
      expression was studied by immunohistochemistry in all patients, and a subset of
      20 patients was studied for allelic loss of heterozygosity and microsatellite
      instability using formalin-fixed, paraffin-embedded tissue. RESULTS: Sixty-one
      percent of patients whose tumors had reduced FHIT expression were dead of
      disease, and 37% of patients whose tumors exhibited preserved FHIT expression
      were dead of disease at 5-year follow-up. Log-rank analysis showed that patients
      retaining FHIT expression had a longer overall survival (P = .03) and disease
      free survival (P = .01). The FHIT expression was not correlated with node status
      or clinical stage. Loss of heterozygosity was seen in 10 (50%) of 20 tumors, low
      levels of microsatellite instability in 4 (20%) of 20 tumors, and high levels of
      microsatellite instability in 1 (5%) of 20 tumors tested. CONCLUSIONS: The FHIT
      gene was associated with a worse survival outcome when its expression was reduced
      in patients with oral cavity squamous cell carcinoma. Loss of heterozygosity in
      the gene was common, but no correlation with protein expression was found.
      Neither loss of heterozygosity nor microsatellite instability was found to
      correlate with survival. Because genomic alterations involving loss of
      heterozygosity of the FHIT gene were not associated with protein expression in
      these tumors, the presence or absence of FHIT expression may be controlled by
      other factors.

PMID- 16454555
TI  - Light-chain-mediated acute tubular interstitial nephritis: a poorly recognized
      pattern of renal disease in patients with plasma cell dyscrasia.
AB  - CONTEXT: Acute renal failure may be the first clinical presentation in patients
      with plasma cell dyscrasia. Recognition of the unusual interstitial inflammatory
      lesion associated with monoclonal light chains and renal failure described herein
      is important to guide clinicians in requesting appropriate tests to confirm
      plasma cell dyscrasia and providing adequate treatment. OBJECTIVE: To describe an
      unusual pattern of tubular interstitial nephritis in patients with underlying
      plasma cell dyscrasia characterized by an interstitial inflammatory reaction
      associated with deposition of light chains along tubular basement membranes.
      DESIGN: Eight cases of light-chain-mediated acute tubular interstitial nephritis
      were identified from the archives of 4296 kidney biopsy specimens. In all cases,
      routine light microscopic examination, direct immunofluorescence, and electron
      microscopic examination were performed. Ultrastructural immunogold labeling was
      performed in specimens with inconclusive findings and in specimens from patients
      with no clinical history of plasma cell dyscrasia. RESULTS: All patients
      presented with acute renal failure. Light microscopy revealed acute tubular
      interstitial nephritis. In some of the cases, direct immunofluorescence and
      electron microscopy failed to show definitive evidence of light-chain deposition
      along tubular basement membranes. Ultrastructural immunogold labeling aided the
      demonstration of monotypical light chains along some tubular basement membranes.
      No light chains were present in other renal compartments. CONCLUSIONS:
      Accumulation of light chains along tubular basement membranes may induce an
      interstitial process that mimics acute tubular interstitial nephritis.
      Recognition of this unusual pattern of renal disease in patients with plasma cell
      dyscrasia requires ancillary diagnostic techniques.

PMID- 16454556
TI  - Hyperleptinemia as a risk factor for high blood pressure in the elderly.
AB  - CONTEXT: Studies have demonstrated that high serum leptin levels are associated
      with aging. However, we do not know whether hyperleptinemia is a relevant risk
      factor for high blood pressure (HBP) in the elderly. OBJECTIVE: To determine the
      relationship between hyperleptinemia and HBP in the elderly. DESIGN: A
      comparative cross-sectional study was carried out in a convenience sample of 70
      healthy elderly persons comprising 46 women (mean age, 67 +/- 5.8 years) and 24
      men (mean age, 73 +/- 7.5 years), and a group of 91 elderly persons with HBP,
      comprising 62 women (mean age, 67 +/- 8.2 years) and 29 men (mean age, 70 +/- 0.3
      years). We measured serum leptin levels through the radioimmunoassay method.
      RESULTS: The elderly subjects with HBP had significantly higher leptin levels
      than the healthy elderly subjects (P = .02). Furthermore, in female elderly
      subjects we observed a statistically significant correlation between systolic
      blood pressure and leptin (r = 0.37, P = .003), as well as systolic blood
      pressure and age (r = 0.29, P = .02), but not with diastolic blood pressure. In
      male elderly subjects, there was no correlation between leptin and systolic blood
      pressure or leptin and diastolic blood pressure. However, hyperleptinemia as risk
      factor for HBP was nearly 5 times higher in men than in women (men, odds ratio =
      18.0, 95% confidence interval 3.2-100.9, P < .001 vs women, odds ratio = 3.33,
      95% confidence interval 1.4-7.4, P = .003). CONCLUSIONS: Our data suggest that
      hyperleptinemia was a significant risk factor for HBP elderly individuals, mainly
      in men.

PMID- 16454557
TI  - Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder
      following lung transplantation is more commonly of host origin.
AB  - CONTEXT: Posttransplantation lymphoproliferative disorder (PTLD) in patients who
      have undergone solid organ transplantation is thought to be mostly of host (ie,
      transplant recipient) origin, as opposed to being predominantly of donor origin,
      which is observed in patients who have undergone bone marrow transplantation.
      Donor-origin PTLDs reportedly follow a more indolent course than host-origin
      PTLDs. OBJECTIVE: To determine the origin of PTLD and its clinical implications
      in patients who have undergone lung transplantation. DESIGN: Patients' medical
      records were reviewed for clinical data. We performed a molecular study to
      determine the origin of abnormal lymphoid cells in 4 PTLD cases identified from
      our autopsy files. Each case underwent restriction fragment length polymorphism
      analysis using polymerase chain reaction-based genotyping for CYP2D6. Epstein
      Barr virus (latent membrane protein 1) immunostaining and polymerase chain
      reaction analysis were performed on PTLD-involved tissues. RESULTS: Three of 4
      PTLD cases were of host origin, and the remaining case was of donor origin.
      Epstein-Barr virus was detected by immunohistochemical and polymerase chain
      reaction methods in all PTLD-involved tissues that were examined. There was no
      apparent difference in clinical manifestations between host-origin and donor
      origin PTLD cases in our study. CONCLUSIONS: The PTLDs in our patients who had
      undergone lung transplantation were Epstein-Barr virus-positive and mostly of
      host origin, without any notable clinical difference from donor-origin PTLD.

PMID- 16454558
TI  - Interference of blood cell lysis on routine coagulation testing.
AB  - CONTEXT: Preanalytical factors influencing the reliability of laboratory testing
      are commonplace. It is traditionally accepted that hemolytic samples are
      unsuitable for coagulation assays because of the release of hemoglobin,
      intracellular components, and thromboplastic substances from damaged blood cells.
      OBJECTIVE: To evaluate the influence of blood cell lysis on routine coagulation
      testing. DESIGN: Twelve aliquots prepared by serial dilutions of homologous
      lysated samples collected from 10 different subjects, and displaying a final
      percentage of lysis ranging from 0% to 9.1%, were tested for prothrombin time,
      activated partial thromboplastin time, fibrinogen, and dimerized plasmin fragment
      D. Lysis was achieved by subjecting citrated whole blood to a freeze-thaw cycle.
      OUTCOME MEASURES: Interference from blood cell lysis on routine coagulation
      testing. RESULTS: Statistically significant increases in prothrombin time and
      dimerized plasmin fragment D were observed in samples containing final lysate
      concentrations of 0.5% and 2.7% respectively, whereas significant decreases were
      observed in activated partial thromboplastin time and fibrinogen in samples
      containing a final lysate concentration of 0.9%. The current analytical quality
      specifications for desirable bias are +/-2.0% for prothrombin time, +/-2.3% for
      activated partial thromboplastin time, and +/-4.8% for fibrinogen. Percent
      variations from the baseline values exceeding the current analytical quality
      specifications for desirable bias were achieved for lysate concentrations of 0.9%
      (prothrombin time and activated partial thromboplastin time) and 1.8%
      (fibrinogen), corresponding to average free plasma hemoglobin concentrations of
      1.7 and 3.4 g/L, respectively. CONCLUSION: Our results confirm that, although
      slightly hemolyzed specimens might still be analyzable, a moderate blood cell
      lysis, as low as 0.9%, influences the reliability of routine coagulation testing.
      Because the interference in coagulation assays has a wide interindividual bias,
      we do not recommend lysis correction and we suggest that the most appropriate
      corrective measure should be free hemoglobin quantification and sample
      recollection.

PMID- 16454559
TI  - BRCA1 and BRCA2 mutation screening using SmartCycler II high-resolution melt
      curve analysis.
AB  - CONTEXT: Real-time polymerase chain reaction technologies have replaced many of
      the more labor-intense methods in the molecular diagnostics laboratory.
      Similarly, melt curve analysis can provide a rapid means of mutation screening.
      OBJECTIVE: To determine if real-time polymerase chain reaction and melt curve
      analysis using the SmartCycler II could be used as a screening tool for 3 common
      mutations in BRCA1 and BRCA2. DESIGN: Real-time polymerase chain reaction
      amplification with SYBR Green I detection was performed on DNA from cell lines
      known to carry the 185delAG or 5382insC mutation in BRCA1 or the 6174delT
      mutation in BRCA2. The melting temperatures and the melt curves were analyzed for
      differences between wild-type DNA and cell lines that were heterozygous for each
      mutation. RESULTS: Significant differences were present in the melt curves for
      each of the mutations compared with those of the wild-type sequences. The melt
      curve for the 185delAG mutation showed a separate peak at a lower temperature,
      which represented the melting temperature of the heteroduplex. For the 6174delT
      mutation, the melt curve had a shoulder at a lower temperature, while the melt
      curve for the 5382insC mutation was shifted to the left and was broader than that
      for the wild-type sequences. CONCLUSIONS: High-resolution melt curve analysis is
      a quick, reliable method for identifying mutations due to small deletions or
      insertions. As a proof of principle, we used this assay to identify the 3 most
      common BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population.

PMID- 16454560
TI  - Longitudinal case-based evaluation of diagnostic competency among pathology
      residents: a statistical approach.
AB  - CONTEXT: Accreditation Council for Graduate Medical Education guidelines require
      the evaluation of residents in 6 competencies. Pathology residents demonstrate
      medical knowledge, patient care, communication, and practice-based learning
      competencies in their attainment of competency in surgical pathology diagnosis.
      OBJECTIVE: To implement a prospective case-based approach to longitudinally
      evaluate the acquisition of competency in surgical pathology diagnosis by
      trainees. DESIGN: Each resident made his or her surgical pathology diagnosis on
      cases before faculty review of the cases. Faculty members scored each resident
      diagnosis as to whether they agree, partially agree, or disagree with the
      diagnosis. Forty-three months of surgical pathology reports (August 2001 through
      January 2005) and 22,252 surgical pathology cases were analyzed. SETTING:
      Pathology residency program. PARTICIPANTS: Thirteen faculty members and 21
      trainees. MAIN OUTCOME MEASURE: Time and training year trends for the number of
      cases reviewed and the percent agreement between faculty and trainees on the
      diagnoses. RESULTS: A mean of 146 cases (range, 12-327 cases) was reviewed during
      each month-long rotation. The number of cases reviewed increased through
      postgraduate year 4. The percent agreement on the diagnoses was 78% (range, 56%-
      99%) for all trainees, with improvement by postgraduate year, although the
      improvement attenuated by postgraduate year 3. Residents were less likely to
      preview the most complex cases. Faculty rank and sex and resident sex did not
      significantly affect outcomes. The overall agreement on the diagnoses increased
      over time. Residents experiencing difficulty could be identified clearly and
      early. CONCLUSIONS: Individual resident performance was easily tracked over time.
      The review of hundreds of reports increases systems accountability and allows
      more objectivity than traditional evaluations. The use of case-based evaluation
      fosters earlier identification and remediation of deficiencies.

PMID- 16454561
TI  - Prostatic glands and urothelial epithelium in a seminal vesicle cyst: report of a
      case and review of pathologic features and prostatic ectopy.
AB  - We report a case of a seminal vesicle cyst containing prostatic glands and
      urothelial epithelium in a patient with no other urogenital anomalies. The
      detection of prostatic tissue, which is of endodermal origin, in a seminal
      vesicle cyst, a mesonephric duct derivative, is unusual. We review the pathologic
      features of seminal vesicle cysts and discuss the histogenesis of prostatic and
      urothelial tissue.

PMID- 16454562
TI  - Radiation-associated extraskeletal osteosarcoma of the chest wall.
AB  - Radiation-associated sarcoma is a rare but potential complication of radiation
      therapy. Most reported cases of osteosarcoma of the chest wall following
      radiation therapy for breast cancer arise from the chest wall skeletal
      structures. In contrast, few cases of extraskeletal osteosarcomas have been
      reported. We report a rare example of an extraskeletal osteosarcoma involving the
      pectoralis major muscle occurring after radiation therapy for breast cancer.
      Extraskeletal osteosarcomas are rare soft tissue tumors with a high rate of local
      recurrence and a poor prognosis.

PMID- 16454563
TI  - Primary mucinous adenocarcinoma of the thymus: a case report and review of the
      literature.
AB  - Primary thymic mucinous adenocarcinoma is extremely rare; to our knowledge, only
      2 cases have been reported to date. We describe a third case of primary mucinous
      adenocarcinoma of the thymus in a 41-year-old man who presented with an anterior
      mediastinal mass with subsequent metastasis to the lung. The initial diagnosis
      was of metastatic mucinous adenocarcinoma, but extensive clinical workup of the
      patient failed to reveal a primary tumor elsewhere in the body. The specific
      identification of mucinous adenocarcinoma as a primary thymic neoplasm can be
      difficult or impossible. Morphologic and immunophenotypic similarities to
      mucinous adenocarcinomas of the gastrointestinal tract can pose diagnostic
      challenges for surgical pathologists, especially in small biopsy specimens.

PMID- 16454564
TI  - Interdigitating dendritic cell sarcoma of the duodenum with rapidly fatal course:
      a case report and review of the literature.
AB  - Interdigitating dendritic cell sarcoma is an extremely rare malignancy derived
      from antigen-presenting cells. Dendritic cells constitute a heterogeneous group
      of cells, which includes Langerhans cells, dermal dendrocytes, follicular
      dendritic cells, and interdigitating dendritic cells present in lymphoid and
      nonlymphoid organs. We report the case of a 36-year-old woman who presented with
      epigastric pain, projectile vomiting, and significant weight loss. Upper
      gastrointestinal endoscopy showed a duodenal lesion; a biopsy of the lesion was
      taken and was diagnosed as sarcoma. She underwent a Whipple procedure. A final
      diagnosis of interdigitating dendritic cell sarcoma was made, with liver and
      peripancreatic lymph node involvement. The patient deteriorated rapidly and died
      4 months later. Although interdigitating dendritic cell sarcoma of the duodenum
      is extremely rare, we think it should be included in the differential diagnosis
      of unusual spindle cell tumors with a rich lymphocytic infiltrate.

PMID- 16454565
TI  - Multiorgan involvement in nephrogenic fibrosing dermopathy: an autopsy case and
      review of the literature.
AB  - Nephrogenic fibrosing dermopathy is a recently recognized, scleromyxedema-like
      fibrosing skin condition that occurs in individuals with acute or chronic renal
      failure. Although the early descriptions of this disorder describe a purely
      cutaneous disease process, 2 recent autopsy reports have identified apparent
      multiorgan fibrosis with involvement of skeletal muscle, myocardium, lungs,
      kidneys, and testes. We describe a 23-year-old man with nephrogenic fibrosing
      dermopathy and significant fibrosis of the atrial myocardium and dura mater,
      which was identified at autopsy. Dural fibrosis is a previously undescribed
      systemic manifestation of nephrogenic fibrosing dermopathy. The literature is
      reviewed.

PMID- 16454566
TI  - Solitary fibrous tumor of the larynx: a case report and review of the literature.
AB  - Solitary fibrous tumors are relatively rare mesenchymal neoplasms that were
      originally described as pleural- or peritoneal-based lesions. Although they were
      considered a form of mesothelioma, subsequent investigation failed to reveal
      mesothelial differentiation. Characterization of their histologic and
      immunohistochemical features, as well as identification in a multitude of
      nonmesothelial-based locations has further served to distinguish these lesions
      from the more diffuse and aggressive mesothelioma. Reports of solitary fibrous
      tumor in the larynx are extremely rare. We report a case of solitary fibrous
      tumor of the larynx in a 38-year-old man.

PMID- 16454567
TI  - A 60-year-old woman with lymphoma and postchemotherapy thickening of the urinary
      bladder wall. Cytomegalovirus cystitis associated with immunosuppression.

PMID- 16454569
TI  - A 74-year-old man with fatal gastrointestinal bleeding. Ruptured Dieulafoy lesion
      or caliber-persistent artery.

PMID- 16454568
TI  - A 68-year-old man with shortness of breath and peripheral edema.
      Angioimmunoblastic T-cell lymphoma.

PMID- 16454570
TI  - A cystic mass in a young woman with presumed polycystic ovarian syndrome.
      Gynandroblastoma.

PMID- 16454573
TI  - A woman with malaise and hyponatremia. Hyponatremia factitia (Munchausen
      syndrome) secondary to desmopressin use.

PMID- 16454574
TI  - Small bowel biopsy in a 6-week-old infant. Microvillous inclusion disease of the
      small intestine.

PMID- 16454576
TI  - A 51-year-old woman with a liver mass. Undifferentiated embryonal sarcoma of the
      liver.

PMID- 16454575
TI  - Neonatal pleural effusion. Spontaneous chylothorax in a newborn with trisomy 21.

PMID- 16454577
TI  - A 70-year-old man with episodes of upper gastrointestinal bleeding. Dieulafoy
      lesion/malformation.

PMID- 16454578
TI  - A 65-year-old woman with a "hemorrhoid". Fibroadenoma of the anogenital region.

PMID- 16454579
TI  - Environmental controls of UV-B radiation in forested streams of northern
      Michigan.
AB  - We examined UV-B radiation flux and its environmental control within and among
      streams of northern Michigan. UV-B flux was estimated in streams by plastic
      dosimetry strips, which allow for the simultaneous and repeated in situ
      measurement of solar radiation. During the summer of 2004, UV-B flux was measured
      across depth gradients and along longitudinal transects in seven streams, which
      were chosen to encompass a range of dissolved organic carbon (DOC) concentrations
      and canopy cover. Attenuation coefficients of UV-B (K(d) (UV-B)) were estimated
      using plastic dosimeters placed along a depth gradient. K(d UV-B) were positively
      correlated with DOC concentration and similar to values obtained with laboratory
      and in situ spectrometry. Along 100 m longitudinal transects, UV-B flux varied
      along all streams regardless of their canopy cover and DOC concentration. Within
      stream fluxes of UV-B were correlated to canopy cover in the only two streams
      that both had relatively low DOC concentration and variable canopy cover. Large
      differences were found among streams in the average UV-B flux (corrected for
      incident solar flux) reaching the dosimeters at 5 cm depth. These among-stream
      differences were largely accounted for by the stream width, canopy cover, and DOC
      concentration. Our results illustrate an inherent variability in UV-B flux within
      and among streams of northern Michigan that is strongly tied to the interactions
      of DOC concentration, stream size and riparian vegetation.

PMID- 16454580
TI  - Influence of human serum albumin on photodegradation of folic acid in solution.
AB  - It has been proposed that photodegradation of folates may be the reason for the
      pigmentation of races living under high fluence rates of ultraviolet radiation.
      The photodegradation of folic acid (FA) induced by ultraviolet-A (UV-A)
      radiation, in solution and in the presence of human serum albumin (HSA), was
      studied with absorption and fluorescence spectroscopy. FA photodegradation, with
      formation of p-aminobenzoyl-l-glutamic acid, 6-formylpterin and pterin-6
      carboxylic acid, was found to follow an exponential trend. A scheme of FA
      photodegradation, which involves photosensitization of FA degradation by its
      photoproducts, was proposed. The rate of FA photodegradation decreased
      drastically in the presence of HSA, whereas the spectral characteristics of the
      photoproducts remained constant. The reduction of the FA photodegradation rate by
      HSA was accompanied by degradation of tryptophan in HSA. Tryptophan, when added
      to solutions of FA, had a similar effect as HSA. In solutions of FA and HSA the
      FA photoproducts cause photodamage mainly to HSA rather than to FA itself. The
      oxygen dependence of FA photodegradation and the inhibition of this process by
      sodium azide indicate that singlet oxygen may participate in the photosensitizing
      activity of FA photoproducts.

PMID- 16454581
TI  - [Reengineering in the process of management and innovation in medical assistance
      at the hospital].

PMID- 16454582
TI  - [Impact of automatized systems in a high resolution model of outpatients
      clinics].
AB  - OBJECTIVE: To analyse the impact of computerised systems in Radiology and
      Laboratory Departments on the reduction in the waiting time of the patients
      attending to an Internal Medicine outpatient consultation organised in a high
      resolution model. METHODS: For one year, we studied the delay in diagnostic
      explorations (laboratory test, simple radiology, ultrasonic diagnostics and brain
      scanner) that were all applied for and performed in a single day. We compared the
      traditional organization (n = 312 explorations), in which the results were handed
      in by hospital auxiliary staff, to a computerised method (n = 457 explorations),
      which was implemented via our intranet. RESULTS: The global delay decreased 10%
      in average, the differences being significant only for the variables "brain
      scanner" (12.7%) and "laboratory" (19%). The average reduction in the waiting
      time per patient was 11.7%, ranging from 7.8% (when only one exploration was
      performed) to 13.2% (when 2 explorations were carried out). The percentage of
      patients who needed to wait more than 3 hours to receive their results also
      diminished significantly. CONCLUSION: The implementation of computerised systems
      reduced the waiting time to receive the results of complementary explorations.
      However, our results were not homogeneous for the different explorations.

PMID- 16454583
TI  - [Do women demand to be assisted at medical clinics more often than men?].
AB  - BACKGROUND: Different features of the users of the Spanish Public Health System
      have been previously assessed, specially in General Practice and Hospital
      Emergency Departments. Nevertheless, the epidemiological characteristics of those
      patients who attend to specialised clinics have not been so thoroughly evaluated.
      PATIENTS AND METHODS: The referee of the demand, the place of residence, the age
      and the sex of patients were all analysed for the ,first visits, at the Medical
      Department clinics (Internal Medicine, Cardiology, Gastroenterology, Pneumology)
      in our hospital, during 2002. RESULTS: A total of 7,486 demands for attention
      (53.3% were women) were asked for by 5,841 patients (52.8%) were women. When
      analysing the variable, place of residence, we find women asked for more
      frequently than men, in the categories of General Practice Department and age
      less than 60 years. Those patients coming from urban areas were more in
      percentage than those coming from rural areas. Whereas the, index of frequency,
      was higher in women than in men, however, there were no differences between urban
      and rural areas. CONCLUSION: In our targeted population we have observed a higher
      demand for medical clinics in women, though the actual demand will depend on
      factors such as age, place of residence and the referee.

PMID- 16454584
TI  - [Degree of fulfillment of the objectives of metabolic control and cardiovascular
      risk factors in patients with type 2 diabetes in an area of primary attention].
AB  - Diabetes mellitus type is one of de most important health problem in the world,
      due to its high prevalence and morbidity and its relation with several
      cardiovascular risk factors. That s why a global action, aimed to prevent these
      vascular syndromes, is needed. OBJECTIVE: the goal of this study is to detect and
      determine how cardiovascular risk factor are controlled in diabetic type 2
      patients, according to the date supplied by several international organization
      that have been studied at a Health Centre of Valladolid. METHODS: It is a
      descriptive cross-sectional study to evaluate the control of several
      cardiovascular risk factors in diabetic patients according to the different
      established criteria. The sample is formed by 74 adult patients (41 men and 33
      women), included in the Diabetes Mellitus Program at Health Centre of Rondilla 2,
      at East Area of Primary Care of Valladolid, in the programmed consultation of
      cardiovascular risk factors control. RESULTS AND CONCLUSION: I has been observed
      that the majority of these cardiovascular risk factors are not well controlled.
      In this way, stringent measures of control should be considered in order to
      prevent the cardiovascular complications related to them.

PMID- 16454585
TI  - [Medicine in the adolescent].
AB  - The biologic, cognitive and sociocultural changes that occur during adolescence
      include a wide range such as to be best treated by internists, but focus in old
      ages is increasing and younger are being treated by others specialists. We review
      the data of those adolescents attended in our Hospital and discuss Internal
      Medicine interest in adolescents. MATERIAL AND METHODS: Epidemiological data, and
      clinical status of those patients between 15 and 21 years old admitted in our
      hospital during the period 1996-2002 were analysed. RESULTS: 5894 admissions of
      adolescent s patients were made in this period. 1326 (23%) where attended in the
      Internal Medicine Department. 755 (57%) were male. Main causes of admission were
      infectious diseases, (mostly urinary tract and respiratory infections). Tobacco
      and alcohol abuse were present in 160 (6%) patients. DISCUSSION: Adolescence
      marks the transition from childhood to adulthood. Health problems and deaths
      among adolescents and young adults result from accidents (mostly from motor
      vehicle), but there are conditions usually matter of our speciality. A
      significant number of patients are been attended by Paediatrics Department and
      such a speciality as Adolescence Medicine is mostly integrated by paediatric
      specialists. We consider as this paper show, these ages ranges are clearly matter
      of our specialty and best treated by internists, but probably need a better
      consideration in our training. The opportunity to incorporate more adolescents
      into practice if realized, could prove challenging for internists.

PMID- 16454587
TI  - [Plasma cell leukaemia: a rare variant of multiple myeloma. A case report].
AB  - Plasma cell leukaemia is a rare variant of multiple myeloma (2-3%), with an
      aggressive disease with short survival. It is defined as circulating peripheral
      blood plasma cells exceeding 2.000/ul and 20% of peripheral blood white cells. We
      present the case of 32-years-old man with left chest-wall pain, hepatomegaly,
      righ cervical adenopathy, 8800 leukocytes/ul with 33% of lymphocytes and 40% of
      plasma cell, 10.8 g/dl of proteins and a monoclonal hypergammaglobulinemia. Bone
      marrow biopsy showed 40-50 % of intramedullary plasma cell. There was a Ig G
      kappa paraproteinemia.

PMID- 16454586
TI  - [Alveolar haemorrhage and hepatitis virus C related mixed cryoglobulinemia.
      Report of three cases].
AB  - Hepatitis C virus -related mixed cryoglobulinemia is a recognised entity. Renal
      and pulmonary involvements are severe potential complications of this disease.
      Alveolar haemorrhage is a form of pulmonary complication. The clinical features
      of the alveolar haemorrhage can mimic other pulmonary diseases. We present three
      patients with hepatitis C virus-related mixed cryoglobulinemia associated to
      pulmonary symptoms that turned to be caused by an alveolar haemorrhage. The first
      patient was a 71-year old woman that was admitted because of hemoptysis and
      severe dyspnea that required mechanical ventilation. Although a pneumonia was the
      initial diagnoses, an alveolar haemorrhage was soon suspected based on the
      persistence of the pulmonary radiological infiltrates despite an adequate
      empirical antibiotic treatment and the presence of a progressive anemization. A
      fibrobronchoscopy, performed 48 hours after treatment was begun, revealed the
      presence of a 6% of hemosiderophages. The second patient was a 64 years old woman
      admitted because of dyspnea, vasculitic cutaneous lesions in gluteus and kidney
      failure. A severe pneumonia was suspected, antibiotic treatment was started and
      again the patient needed mechanical ventilation. The fibrobronchoscopy
      demonstrated the existence of a 60% of hemosiderophages. The third case describes
      a 67 year old woman that complained of fever, dyspnea and right chest pain.
      Similarly to the previous cases a severe pneumonia was the initial diagnoses, the
      patient needed to be transferred to the intensive care unit and mechanical
      ventilation was finally required. The fibrobronchoscopy showed remains of blood
      suggestive of an alveolar haemorrhage.

PMID- 16454588
TI  - [Fever and hyperprolactinaemia as the onset of Langerhans cell histiocytosis].
AB  - Langerhan's cell histiocytosis (LCH) is a rare disorder in which granulomatous
      deposits occur at multiple sites within the body. The aetiology is unknown. Is
      more frequent in children. Presenting symptoms are polyuria and polydipsia, due
      to diabetes insipidus, other symptoms are skin rash, dyspnea and tachypnea.
      Diagnosis is reached by biopsy of lesions, in which Langerhan's cell are found.
      Prognosis is variable, depending the site affected; therefore, treatment must be
      individually. The hyperprolactinaemia in LCH is very rare and its related with
      anterior pituitary deficiency. There are not many cases described, all of them
      during the course of the disease, not as the onset. We describe a 22 year-old
      woman with Langerhan's cell histiocytosis which initial presentation was fever
      and hyperprolactinaemia.

PMID- 16454589
TI  - [Chagasic cardiomyopathy in Spain: a diagnosis to bear in mind].
AB  - Chagas' disease is an important public health problem in Latin America and one of
      the specific causes of dilated cardiomyopathy. Chronic chagasic cardiomyopathy is
      the worse result of this disease and its main cause of mortality. Rural
      migrations from endemic to nonendemic countries make possible observing affected
      patients in United States and Europe. We report the case of a patient with
      congestive heart failure who was diagnosed with chronic chagasic cardiomyopathy.
      This is the first case of chagasic dilated cardiomyopathy in Spain.

PMID- 16454590
TI  - [Lemierre's syndrome and Mycoplasma pneumoniae].
AB  - It has been suggested that a previous viral or bacterial pharyngitis may
      predispose to Lemierre's syndrome, an uncommon entity nowadays. A case of
      Lemierre's syndrome and co-infection with Mycoplasma pneumoniae is described,
      association published before in only 2 other cases. A 16-year-old girl with
      trombophlebitis of the left jugular vein, Fusobacterium necrophorum bacteremia
      and septic emboli in the lung requiring mechanical ventilation due to severe
      respiratory insufficiency. Despite early treatment with penicillin G and
      clindamycin, fever and part of pulmonary affectation persisted until that an
      antibiotic agent active against M. pneumoniae was instaurated, after its
      serological confirmation. The physicians should be easily recognized this disease
      because of its characteristic clinical findings, and co-infection with other
      organisms including M. pneumoniae, should be considered.

PMID- 16454592
TI  - [Leptospirosis in Asturias].

PMID- 16454591
TI  - [Biphosphonates in oncology].
AB  - Biophosphonates are analogues of pyrophosphate. The mechanism of action of
      bisphosphates is the inhibition of osteoclast activation (antiresorptive
      mechanism). The oral bioavailability of biophosphonates is only about 1-2%, and
      because of gastrointestinal side effects (mainly esophageal irritation), oral
      agents are less useful in oncology. Biophosphonates are used for the treatment of
      Paget s disease of bone, the prevention of osteoporosis, and in another clinical
      scenarios as the prevention of bone disease after organ transplantation. In
      clinical oncology biophosphonates are used for the treatment of hypercalcemia of
      malignancy, prevention and treatment of bone events related to bone metastases,
      and in the prevention of osteoporosis related to breast cancer. According to
      American Society of Clinical Oncology (ACO) guidelines, biophosphonates should be
      used in hypercalcemia of malignancy and bone events related to metastases of
      breast cancer and multiple myeloma.

PMID- 16454593
TI  - [Mission of Internal Medicine and its influence in hospitals].

PMID- 16454594
TI  - [Temporal evolution of platelets and anti-platelet antibodies in patients of
      endemic area with non complicated malaria].
AB  - AIM: To evaluate the number of platelets and the title of anti-platelet
      antibodies IgG Ac-PI (by flow cytometry) in patients with non-complicated
      malaria. METHODS: Descriptive, prospective and longitudinal study from 45
      patients (aged among 14-67). Thirty patients were followed during 7 days.
      RESULTS: A) Pretreatment: it was found malarial thrombocytopenia (MT) in 71 % and
      significant association between MT and Ac-PI in 33 %. MT was not associated to
      residence zone, to have had malaria in the last year and Plasmodium species but
      sex associated (males, p= 0.02078195), although, the Ac-PI titers of male and
      female was similar. Correspondingly, the number of platelets was statistically
      similar to the values of above variables. There was a low and an inverse lineal
      correlation between platelets and titres of Ac-P1 (r= -0.342 (p= 0.02310)). B)
      During the following, multiple linear regression among platelets, age, years of
      residence in the zone, number of malaria episodes in the last year, parasitaemia
      (logarithmically expressed) and Ac-P1 titers showed no significant coefficient
      and the maximum explanation achieved (17%) was parasitaemia and Ac-P1 titers.
      Similar analysis among Ac-P1 and age, years of residence in the zone number of
      malaria episodes in the last year, parasitaemia (logarithmically expressed)
      showed that the first three explain 38 % of the changes in Ac-P1, whereas malaria
      episodes and years of residence in the zone explain 28%.

PMID- 16454596
TI  - [Antiretroviral pharmaceutical expenditure and possibilities for optimization].
AB  - INTRODUCTION: A lack of treatment compliance, resistances and non-advanced stages
      of the disease are the reasons why not all HIV-infected patients benefit from the
      demonstrated efficacy of antiretroviral drug combinations--with the consequent
      important increase in costs. A prospective cohort follow-up study is conducted to
      analyze the distribution of antiretroviral pharmaceutical expenditure in a
      district hospital, and the possibilities for improving its efficiency. MATERIAL
      AND METHODS: The study comprised 128 HIV-infected patients seen for 12
      consecutive weeks (September to November, 2004). The characteristics of previous
      follow-up were analyzed, and the patients were divided into groups according to
      the course over the following weeks and the results of prescribed treatment:
      group 1 (effective treatment), group 2 (ineffective treatment), and group 3
      (treatment dropout). Based on the prescription history, corroborated with drug
      retrieval and the acquisition costs (FARMASYS software), the cost of
      antiretroviral medication was calculated for each of the 108 patients receiving
      highly active antiretroviral therapy (HAART). The statistical analysis was
      carried out with the SPSS version 11.5 statistical package, and considering
      statistical significance for p < 0.05. RESULTS: The cost generated by the 108
      patients included during the study period who received HAART was 232,366 euros,
      with an average of 2,151 euros per patient and 19,363 euros per day of
      consultation. The distribution of patients and of the costs generated by the
      above defined groups was as follows: group 1: 79 patients (80.6%); group 2: 11
      patients (10.6%); group 3: 18 patients (8.8%). In the group 1 patients, 15.2% of
      the antiretroviral expenditure corresponded to patients who had started therapy
      with a CD4+ count of > 350 cells/ml, while 45% had > 350 cells/ml at the present
      time, and 25.9% had > 500 cells/ml. Previous medication dropout was identified as
      a predictor of new dropouts and treatment failures. COMMENT: While the cost
      generated by antiretroviral medication is high, 19.4% is administered to patients
      who do not benefit from such treatment due to a lack of efficacy or dropouts, and
      in another 40-60% of cases the need for such treatment could be subject to
      consideration in view of the good immune status of the patients.

PMID- 16454595
TI  - [HIV-1 infection, use of drugs and neuropsychologic efficiency].
AB  - INTRODUCTION: The abuse of substances has been considered as an explanatory
      factor of the neuropsychologic failure. However, doubts persist on the
      distinction among direct or indirect effects and even on the interaction between
      the effect of the HIV and the use of substances. The objective of this
      investigation consisted on studying the effect of the use of drugs and the
      seropositivity to the HIV-1 on the neuropsychologic efficiency. METHOD: After
      obtaining the informed consent 113 patients they were recruited, integrated in
      four groups (34 seropositives ex-UDPP; 33 seropositives in maintenance programs
      with methadone; 19 seronegatives; and 27 seronegatives without previous use of
      drugs. To all they were applied a neuropsychologic battery designed ad hoc, an
      semistructured interview about sociodemographical, toxicological,
      neuropsychiatric and clinical-biological aspects and an evaluation of the anxious
      depressive symptomatology. RESULTS: The seropositive patients in methadone
      present bigger rates of prevalence of the damage that the rest of the groups (X2
      = 32.22, p < .000) and lower rates of execution in all the studied factors. Also,
      it is observed that the seropositive patients as group present lower execution
      levels and higher rates of damage. Also, all the groups had lower levels of
      execution that the people seronegative non consumers (F = 15.661, p > .000).
      CONCLUSIONS: The abuse of drugs and the seropositivity are factors that associate
      to the decrease neuropsychologic efficiency. Also, the situation regarding the
      abuse explains differences in the execution levels and rates of neuropsychologic
      damage, being the patients in maintenance programs with methadone those that
      present the worst execution levels, as well as the highest rates in
      neuropsychologic affectation.

PMID- 16454597
TI  - [Metformin in the treatment of type 2 diabetes in overweighted or obese
      patients].
AB  - FUNDAMENTALS AND OBJECTIVES: [corrected] Diabetes is the disease that has
      suffered a greater increase in his incidence in the last years. Obesity is the
      most important risk factor to develop this disease and metformin is considered as
      a first line drug in overweighted diabetic patients. The aim of this study is to
      evaluate the use of metformin and the degree of control of the associated
      cardiovascular risk factors (CVRF) in patients suffering of type 2 diabetes and
      overweight or obesity. PATIENTS AND METHODS: This is a transversal descriptive
      study over a random chosen group of 308 patients followed at primary care level.
      They were classified in four different groups depending on the treatment used to
      control them (diet, insulin, metformin and other oral antidiabetic drugs). They
      were evaluated upon the degree of control of the modifiable CVRF, the presence of
      complications and the metabolic control. RESULTS: The average age was 69.6 years,
      54% of the patients female. 36.6% followed treatment with metformin and 40.5%
      with sulfonylureas. The macrovascular percentage of affection was 19.4%. The most
      frequent CVRF was arterial hypertension (76%). The goal levels of control that
      were less in range were the levels of cLDL < 100 mg/dl and systolic blood
      pressure < 130 mmHg. Diabetic patients only treated with diet had a better
      control of fasten glycemia and HbA1c% than those ones treated with metformin (p <
      0.001). The group treated with metformin showed levels of triglycerides (TG)
      significantly higher than those of the diet controlled group (p = 0.009) and
      insulin group (p < 0.001). CONCLUSIONS: Metformin and sulfonylureas are used in a
      similar proportion in type 2 diabetics with overweight or obesity. There is a
      poor control of the majority of the CVRF in the diabetic population studied.

PMID- 16454599
TI  - [Troponin I in patients with pulmonary thromboembolism].
AB  - OBJECTIVE: To study the frequency in patients with pulmonary thromboembolism
      (PTE) of an elevated troponin I and the associated characteristics. MATERIAL AND
      METHODS: Prospective study of 29 consecutive patients with PTE. RESULTS: Troponin
      I was determined in 22 patients. The median age was 78.1 years. Ten (45.5%) had
      an elevated troponin I, with a median level of 1 ng/ml (range 0.7-3.1 ng/ml). The
      diagnostic delay was lower in patients with an elevated troponin I (2 +/- 1.7 vs.
      5.9 +/- 5.6 days, p = 0.04). Three (30%) of 10 patients with an elevated troponin
      I had midthoracic pain. Patients with an elevated troponin I had a higher
      frequency of arterial hypotension (40 vs. 16.7%), respiratory failure (70 vs.
      58.3%) and electrocardiographic overload right heart data (50% vs. 33.3%),
      although without reaching statistical significance. CONCLUSIONS: A slightly
      elevated troponin I is frequent in patients with PTE. The early diagnosis may
      increase the frequency of an elevated troponin I. The coexistence of an elevated
      troponin I and midthoracic pain may simulate an acute coronary syndrome. In
      patients with PTE, an elevated troponin I may associate to some severity criteria
      such as arterial hypotension, respiratory failure and electrocardiographic
      overload right heart data.

PMID- 16454598
TI  - [Induction of tolerance in hypersensitivity to mesalazine (5-ASA)].
AB  - Mesalazine is a derivative of 5-aminosalicylic acid (5-ASA), which is useful in
      the treatment of intestinal inflammatory disease. Sulfasalazine is formed by two
      parts, sulfapyridine and 5-ASA, the latter being the active part of the molecule.
      The new preparatives derived from 5-ASA were developed in an attempt to avoid the
      traditionally associated side effects to sulfapyridine, although they are still
      observed and new effects appear. We present two cases. The first is a man
      diagnosed of inflammatory intestinal disease, with background of two previous
      reactions of urticaria and angioedema after acetyl salicylic acid, who presented
      urticaria after taking mesalazine. The second one had generalized urticaria after
      three months of initiating treatment with mesalazine. Given the need for
      treatment in both cases, a desensitization protocol to mesalazine was made. It
      was developed in 17 days in our service. Tolerance to that drug to therapeutic
      doses is reached. When faced with patients with hypersensitivity to different
      drugs, that are necessary to treat their disease, "desensitization" regimes, that
      assure good tolerance, can be made.

PMID- 16454600
TI  - [Small size choledochocele as a cause of chronic epigastric pain: diagnosis and
      treatment by means of ERCP].
AB  - Choledochocele belongs to type III Alonso-Lej's classification of biliary cysts
      and they are considered the less frequent of such cysts. The definition most
      often given of choledochocele is a cystic dilation of the distal intramural
      portion of the bile duct, protruding into the duodenal lumen. ERCP is one of the
      diagnostic and therapeutic procedures of choice, specially when they are small
      and the cystic cavity is usually collapsed. The ballooning of the papilla during
      contrast injection in ERCP is thought to be a diagnostic sign. We present a
      patient suffering from chronic epigastric pain due to a small choledochocele.
      Magnetic Resonance Cholangiopancreatography failed to diagnose it. ERCP offered
      both diagnosis and treatment by means of biliary sphincterotomy.

PMID- 16454601
TI  - [Atypically located posttraumatic pericardial cyst].
AB  - Pericardial cyst are rare, most of them congenital in origin. They usually are
      located in the cardiophrenic angles, mainly on the right side. Although the most
      frequent clinical presentation is asymptomatic, and the prognosis is benign,
      important complications had been described. For this reason we used to take
      aggressive therapeutic interventions like percutaneous aspiration or surgical
      resection by thoracotomia or thoracoscopy. The case we report is interesting
      because it was an atypically located left upper paramediastinal cyst, and not
      congenital in origin but posttraumatic. The diagnosis was made by imaging
      techniques and we accomplished conservative alternative because of the favourable
      evolution. We think that it should be a good option in case of asymptomatic and
      no complicated cases.

PMID- 16454602
TI  - [Extranodal T/NK-cell lymphoma, nasal type: a case report and review of the
      literature].
AB  - Extranodal T/NK-cell lymphoma, nasal type: a case report and review of the
      literature. Extranodal NK/T-cell lymphoma, nasal type, is an extranodal lymphoma,
      usually with an NK-cell phenotype and EBV positive, with a broad morphologic
      spectrum, frequent necrosis and angioinvasion, and most commonly presenting in
      the midfacial region, but also in other extranodal sites. We present the case of
      a 42-years old-man with a intranasal mass, left cervical adenopathies and
      indolent thrombocytosis. The biopsy of the nasal mass showed a diffuse infiltrate
      of medium-sized lymphoid cells, with slightly irregular nuclei and moderate
      polymorphous. The immunophenotype of tumor cells was CD45+, cCD3+, Granzyme B+,
      CD56+, CD20-,CD4-,CD8-, LMP1(EBV)-. The diagnosis of the case was Extranodal T/NK
      cell lymphoma, nasal type. There was not disseminated disease in the extent
      studies. With the diagnosis of localized extranodal T/NK-cell lymphoma and
      reactive thrombocytosis, the patient was treated with chemotherapy and sequential
      radiotherapy, followed by bone marrow transplantation.

PMID- 16454603
TI  - [Intrahepatic cholestasis caused by amoxicillin-clavulanic acid].

PMID- 16454604
TI  - Cost-effectiveness of abdominal ultrasonography in the diagnosis of colorectal
      carcinoma.

PMID- 16454605
TI  - Long-term evolution of liver histopathology in patients with chronic hepatitis C
      and sustained response.
AB  - OBJECTIVE: To evaluate the evolution of histological changes observed in patients
      with chronic hepatitis C (CHC) and sustained response (SR) compared to non
      responders (NR) to antiviral treatment. METHODS: A retrospective study was
      performed in a total of 176 patients with CHC. These were divided into two
      groups: 132 SR and 44 NR. All had undergone a basal liver biopsy prior to
      treatment onset. A second biopsy was performed in 143 patients, 104 SR and 39 NR.
      Inflammatory activity and the degree of liver fibrosis was measured by Metavir
      units (MU). The progression and regression index of fibrosis was calculated
      before and after treatment. The time elapsed between the two biopsies was 5.9 +/-
      0.3 years for SR and 6.6 +/- 0.3 years for NR (NS). RESULTS: At baseline, 53% of
      SR patients had mild, chronic active hepatitis (CAH), while this was moderate in
      43% of NR patients (p < 0.0001). The time elapsed between baseline and post
      treatment liver biopsies was 5.9 +/- 0.3 years for SR subjects and 6.6 +/- 0.4
      years for NR subjects (NS). After antiviral treatment 47% of SR subjects
      presented a normal liver or minimal changes, whilst mild CAH persisted in 34.4%
      and moderate CAH in 37.5% of NR subjects. Necro-inflammatory activity decreased
      by 50% in SR subjects and by 15% in NR subjects (p < 0.0001), and fibrosis
      decreased by 82% in SR subjects (p < 0.0001) and by 66% in NR subjects (p <
      0.001). Fibrosis progression index was 0.14 MU/year in SR subjects and 0.21
      MU/year in NR subjects (NS). Fibrosis regression index was -0.11 in SR subjects
      and -0.14 in NR subjects (NS). CONCLUSIONS: In our series of patients with CHC
      and SR, we observed histological normalization in approximately fifty per cent of
      cases during long-term follow-up. NR subjects also showed improvement, especially
      in the fibrosis score. Both groups showed a marked regression of liver fibrosis
      after treatment.

PMID- 16454606
TI  - The value of colonoscopy to assess rectal bleeding in patients referred from
      Primary Care Units.
AB  - OBJECTIVES: Rectal bleeding is very common in the general population. It is
      produced mainly because of benign disease originating in the anus and the rectum.
      Our aim was to evaluate the need for colonoscopy in patients presenting with
      rectal bleeding. PATIENTS AND METHODS: Patients referred from Primary Care Units
      and complaining of rectal bleeding were included prospectively in a three-month
      study. All patients underwent a careful medical history along with physical
      examination, laboratory tests, and colonoscopy. RESULTS: 126 patients with a mean
      age of 49.2 years (range: 19-80) were studied. Rectal digital examination was
      abnormal in 75 cases (59.5%). Severe disease was encountered in 22 patients
      (neoplasm, angiodysplasia, and inflammatory bowel disease); 10 patients had
      polyps, 6 had colorectal cancer, and 6 had inflammatory bowel disease. Out of 63
      patients younger than 50 years, 5 had severe disease, all of them in the form of
      inflammatory bowel disease. CONCLUSIONS: A neoplasm of the rectum and colon in
      patients younger than 50 years is a rare event. A colonoscopy must be performed
      in this group of patients to rule out inflammatory bowel disease.

PMID- 16454607
TI  - The value of abdominal ultrasound in the diagnosis of colon cancer.
AB  - INTRODUCTION: Colon cancer is one of the main causes of cancer death. Diagnosis
      requires the examination of the entire large bowel by means of radiological or
      endoscopic techniques. Many patients suspect of colon cancer are referred for
      colonoscopy but nevertheless this suspicion is not confirmed after endoscopic
      examination. The objective of this study is the evaluation of the reliability of
      abdominal ultrasound in the diagnosis of these tumors. MATERIAL AND METHOD: We
      selected patients suspect of colon cancer referred to the endoscopy unit for a
      colonoscopy. An abdominal ultrasound was carried out on all patients prior to the
      endoscopy. Considering the endoscopic examination as a gold standard, the
      sensibility, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of the ultrasonography were evaluated. Likewise, a series of
      analytical and clinical parameters were evaluated, in an attempt to establish
      associated factors of a colon cancer. The statistical analysis was carried out by
      means of the statistical package SPSS 12.0 for Windows. RESULTS: 145 patients
      were included in the study (56.6% males) with an average 66.72 years of age (22
      89). A cancer was diagnosed in 42 cases (28.9%). In the diagnosis of colon
      cancer, abdominal ultrasound presents a sensitivity of 79.06%, a specificity of
      92.15%, a PPV and a NPV of 80.9% and of 91.2%, respectively. Excluding from the
      analysis lesions of the rectal ampulla, which cannot be adequately evaluated by
      means of ultrasound, the figures for sensitivity, specificity, PPV and NPV
      increase to 91.8, 92.1, 80.9 and 96.9% respectively. The univariate analysis
      showed that an age over 65 years and the presence of microcytosis are associated
      to a greater risk of colon cancer while after multivariate analysis only the
      presence of microcytosis resulted to be an independent predictive factor of
      cancer. CONCLUSIONS: Abdominal ultrasound presents high sensitivity, specificity,
      PPV and NPV in the diagnosis of colon cancer. The combination of an
      ultrasonography and a rectoscopy permits us to rule out the presence of a
      colorectal carcinoma. In patients with microcytosis of 65 years and over, if
      there is strong clinical suspicion, a negative ultrasound may not be sufficient
      to rule out a colorectal neoplasia.

PMID- 16454608
TI  - Relationship between socio-demographic and clinical variables, and health-related
      quality of life in patients with inflammatory bowel disease.
AB  - OBJECTIVE: The principal aim of the present study is to evaluate the influence of
      socio-demographic and clinical variables on health-related quality of life (HRQL)
      in patients with inflammatory bowel disease. PATIENTS AND METHOD: This was a
      cross-sectional study. health-related quality of life was measured with the
      Inflammatory Bowel Disease Questionnaire (IBDQ). A total of 120 patients, 60 with
      ulcerative colitis and 60 with Crohn s disease, participated in the study.
      RESULTS: No significant differences were observed between ulcerative colitis and
      Crohn s disease patients in IBDQ dimensions. However, a multivariate analysis
      revealed that sex, type of treatment, extraintestinal symptoms, number of
      relapses in previous year, satisfaction with surgery, and need for psychological
      support were related to HRQL. CONCLUSIONS: The identification of these variables
      associated with HRQL in patients with inflammatory bowel disease shows them to be
      basically non-disease factors. Knowledge of such elements can turn out to be very
      useful in order to guide future research and modify specific factors in further
      interventions.

PMID- 16454609
TI  - Endoscopic ultrasonography with fine-needle aspiration: present situation and
      indications.
AB  - Endoscopic ultrasonography with fine-needle aspiration is a safe technique that
      allows the collection of tissue samples for histological diagnosis, as well as
      therapeutic maneuvers. It has better diagnostic accuracy versus other exploration
      techniques used for the staging of neoplasms in the gastrointestinal tract as
      well as in other organs. The risk for complications is extremely low, and the
      procedure has been shown to be cost-effective in many studies. In this paper we
      attempt to review the main present indications of endoscopic ultrasonography with
      fine-needle aspiration.

PMID- 16454610
TI  - Celiac disease (CD), ulcerative colitis (UC), and primary sclerosing cholangitis
      (PSC) in one patient: a family study.
AB  - We discuss the case of a 17-year-old male who at the age of 7 was diagnosed with
      celiac disease (CD) together with ulcerative colitis (UC) and primary sclerosing
      cholangitis (PSC). The patient was treated with gluten-free diet and
      immunosuppressive drugs (azathioprine), and currently remains asymptomatic. The
      patient's younger, 12-year-old sister was diagnosed with CD when she was 1.5
      years old, and at 7 years she developed type-I diabetes mellitus, which was
      difficult to control. A family study was made, and both parents were found to be
      affected with silent CD. All were DQ2 (+). In relation to the case and family
      study, we provide a series of comments related to CD and its complications.

PMID- 16454611
TI  - Intestinal occlusion secondary to transverse colon volvulus.

PMID- 16454612
TI  - [Diagnosis and treatment of a vascular malformation in the jejunum by
      laparoscopy].

PMID- 16454614
TI  - [Rapunzel syndrome].

PMID- 16454613
TI  - [Progressive myoclonic ataxia associated with antibodies against Purkinje cells
      in a celiac patient].

PMID- 16454615
TI  - [Malignant melanoma of primary origin].

PMID- 16454616
TI  - [Obstructive jaundice secondary to lymphoplasmocytic cholangitis. Differential
      diagnosis of Klatskin tumors].

PMID- 16454617
TI  - [Hepatobiliary cystadenoma with mesenchymal stroma, a hormone dependent
      neoplasm?].

PMID- 16454619
TI  - Improving the supervision of therapy assistants in Western Australia: the Therapy
      Assistant Project (TAP).
AB  - INTRODUCTION: Multidisciplinary therapy assistants (TAs) are increasingly seen as
      a model suited to the provision of allied health services in rural and remote
      areas. Supervision is a key aspect of therapy assistant practice. The rural
      context presents many challenges in supervising TAs including: a
      multidisciplinary TA role, outreach service delivery models, inexperienced allied
      health professionals (AHPs) and a high turnover of AHPs. At present there are no
      accepted standards for supervising TAs in this context. This study aimed to
      improve the supervision of TAs by AHPs in a rural setting. Improving supervision
      formed one aspect of the Therapy Assistant Project (TAP). METHODS: Minimum
      standards for supervision were developed, a process for recording TA supervision
      introduced, and training in supervision skills was delivered to AHPs. A mixed
      method study design was used to determine the impact of introducing minimum
      standards and supervisor training on supervision practices. RESULTS: Minimum
      supervision standards included: program and administrative discussion,
      observation, and demonstration of therapy sessions. Methods recommended for
      supervising allowed regular supervision of TAs in small, distant rural towns.
      Developing minimum standards for supervision, a process for recording
      supervision, and training in supervisory skills resulted in increased supervision
      between AHPs and TAs. AHP and TA participants expressed satisfaction with minimum
      supervision standards. The frequency and amount of supervision increased although
      videoconferencing for supervising TAs in distant towns was not widely used for
      supervision. CONCLUSION: This study provides a new resource for supervision
      practices for rural TAs. The minimum standards for supervision would be a
      suitable resource to assist health services seeking to improve supervision of TAs
      or commencing a TA program. Further exploration of the use of videoconferencing
      for supervising TAs in distant rural towns is suggested. Training in supervision
      skills for AHPs should include introductory and complex supervision methods. This
      study represents one step in defining standards for rural and remote TA practice.

PMID- 16454621
TI  - NIH requests information on care of laboratory animals.

PMID- 16454622
TI  - Comparison of an indirect immunofluorescence assay, western blot analysis, and a
      commercially available ELISA for detection of Ehrlichia canis antibodies in
      canine sera.
AB  - OBJECTIVE: To examine the correlation between results for an indirect
      immunofluorescence assay (IFA) that uses Ehrlichia canis antigen as a substrate
      (ie, E canis-IFA), 2 western blot (WB) analyses, and a commercially available
      ELISA in the detection of E canis antibody in dog sera. SAMPLE POPULATION: 54
      canine serum samples that were reactive on E canis-IFA and 16 canine serum
      samples that were E canis-IFA nonreactive. PROCEDURE: Serum samples were
      evaluated by use of 2 WB analyses and a commercially available ELISA. Correlation
      between results of the 3 testing modalities (ie, IFA, WB analyses, and the ELISA)
      was examined by use of nonreactive (E canis-IFA reciprocal titer, < 20), low
      titer (reciprocal titer, 80 to 160), medium-titer (reciprocal titer, 320 to
      2,560), and high-titer (reciprocal titer, 5,120 to > 20,480) serum samples.
      RESULTS: For all serum samples in the nonreactive (n = 16), medium-titer (17),
      and high-titer (18) groups, correlation of results among IFA, WB analyses, and
      the commercially available ELISA was excellent. A poor correlation was found
      between IFA results and those of WB analyses and the ELISA for serum samples in
      the low-titer group (19), with only 4 of the 19 serum samples having positive
      results on both WB analyses and the commercially available ELISA. CONCLUSIONS AND
      CLINICAL RELEVANCE: The discrepancy between E canis-IFA, WB analyses, and the
      commercially available ELISA results for the low-titer serum samples may be
      related to a high IFA sensitivity or, more likely, a lack of specificity
      associated with cross-reactivity among Ehrlichia spp.

PMID- 16454623
TI  - Assessment of the geometry of the cubital (elbow) joint of dogs by use of
      magnetic resonance imaging.
AB  - OBJECTIVE: To assess joint geometry and highlight potential evidence of
      physiologic incongruity in cubital (elbow) joints of large, small, and
      chondrodystrophic breeds of dogs. SAMPLE POPULATION: Nonarthritic elbow joints
      obtained from cadavers of mature dogs of large breeds (n = 19), small breeds
      (14), or chondrodystrophic breeds (8). PROCEDURE: Magnetic resonance imaging was
      used to quantify interosseous gaps at 6 defined positions and 2 sagittal planes
      of the humeroantebrachial region by use of a fat-suppressed 3-dimensional
      gradient-echo sequence. RESULTS: Interosseous gaps in the more medially located
      sagittal plane were significantly narrower at the level of the anconeal process
      than at any other position of the joint in large-breed dogs, compared with
      results for small- or chondrodystrophic-breed dogs. In both sagittal planes, the
      gaps were significantly wider at the center of the ulnar trochlear notch than at
      any other position. Significant correlation between body weight and width of the
      interosseous gaps was found only in large-breed dogs and was found in both
      sagittal planes at the center of the ulnar trochlear notch (r, 0.834 and r,
      0.680, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: In large-breed dogs,
      the interosseous gap was especially narrow at the level of the anconeal process
      and its diametric position. This suggests less ability to compensate intra
      articular steps in dogs with short ulna syndrome, which predisposes to failure of
      the union between the anconeal process and olecranon. Geometric incongruity may
      be regarded as clinically normal in nonarthritic humeroulnar joints. The degree
      of geometric incongruity increases with body weight.

PMID- 16454624
TI  - Effect of body position on cranial migration of epidurally injected methylene
      blue in recumbent dogs.
AB  - OBJECTIVE: To determine the relationship between different body positions during
      recumbency on the cranial migration of epidurally injected methylene blue in
      canine cadavers. SAMPLE POPULATION: 21 fresh cadavers of clinically normal adult
      female mixed-breed dogs. PROCEDURE: Dogs were randomly assigned to the following
      3 groups: dogs remaining in right lateral recumbency (n = 7), dogs rotated from
      left to right lateral recumbency (7), and dogs rotated from dorsal to right
      lateral recumbency (7). Each dog received an epidural injection of 0.05%
      methylene blue (0.1 mL/kg) at the lumbosacral space. A dorsal laminectomy of the
      vertebral column was made, and cranial extent of methylene blue in 4 quadrants
      (right lateral, left lateral, ventral, and dorsal) was determined by examining
      dura mater staining. RESULTS: No significant difference was found among groups in
      regard to body weight or body condition score. Epidural cranial migration of
      methylene blue in the right lateral quadrant was significantly greater in dogs
      that remained in right lateral recumbency than in dogs that were rotated from
      left to right lateral recumbency. No significant difference was found within
      groups for epidural cranial migration of methylene blue between each quadrant. No
      significant relationship was found between body weight or body condition score
      and epidural cranial migration of methylene blue. CONCLUSIONS AND CLINICAL
      RELEVANCE: Body positioning and amount of recumbency time influence cranial
      migration of epidurally injected methylene blue. If greater cranial migration of
      an epidurally administered drug is desired, placing the patient in lateral
      recumbency with the surgical site on the dependent side may precede surgery.

PMID- 16454625
TI  - Effects of preoperative epidural administration of racemic ketamine for analgesia
      in sheep undergoing surgery.
AB  - OBJECTIVE: To investigate the effects of preoperative epidural administration of
      racemic ketamine to provide analgesia in sheep undergoing experimental hind limb
      orthopedic surgery. ANIMALS: 12 adult sheep (weight range, 51.4 to 67.2 kg).
      PROCEDURE: Sheep were anesthetized with guaifenesin, thiopental, and isoflurane;
      after induction of anesthesia, sheep received a lumbosacral epidural injection of
      ketamine (1 mg/kg; n = 6) or saline (0.9% NaCl) solution (1 mL/7 kg; 6 [control
      group]). Respiratory and cardiovascular variables were recorded before and at
      intervals during and for 6 hours after anesthesia. During that 6-hour
      postoperative period, analgesia was evaluated subjectively with a numeric ranking
      scale that included assessments of comfort, posture, movement, and response to
      wound palpation; buprenorphine was administered when a score > 3 (maximum score,
      10) was achieved. Rectal temperature, heart and respiratory rates, and lameness
      were evaluated daily for 2 weeks after surgery. RESULTS: At all evaluations,
      cardiovascular and respiratory variables were comparable between the 2 groups.
      Compared with control sheep, time to first administration of rescue analgesic was
      significantly longer and total dose of buprenorphine administered during the 6-
      hour postoperative period was significantly decreased for ketamine-treated sheep.
      During the second week following surgery, ketamine-treated sheep had
      significantly less lameness than control sheep. CONCLUSIONS AND CLINICAL
      RELEVANCE: In sheep undergoing hind limb surgery, preoperative epidural
      administration of ketamine appears to provide analgesia in the immediate
      postoperative period and has residual analgesic effects, which may contribute to
      more rapid return of normal function in surgically treated limbs.

PMID- 16454626
TI  - Role of coresistance in the development of resistance to chloramphenicol in
      Escherichia coli isolated from sick cattle and pigs.
AB  - OBJECTIVE: To determine the cause of persistent resistance to chloramphenicol
      (CP) after the ban on its use in food-producing animals in several countries.
      SAMPLE POPULATION: 71 CP-resistant and 104 CP-susceptible Escherichia coli
      strains isolated from sick cattle and pigs in Japan. PROCEDURE: Susceptibility of
      all bacterial strains to thiamphenicol (TP) and florfenicol (FFC) was tested by
      use of an agar dilution method. The CP-resistance genes and variable region
      within class 1 integrons in CP-resistant strains were identified by use of a PCR
      assay. RESULTS: The CP acetyltransferase gene (ie, cat1) was identified as the
      predominant CP-resistance gene in strains isolated from cattle, and the cat1and
      nonenzymatic CP-resistance gene (ie, cmlA) were the predominant CP-resistance
      genes in strains isolated from pigs. Additionally, strains with cat1 isolated
      from cattle often were resistant to ampicillin, dihydrostreptomycin (DSM),
      oxytetracycline, and trimethoprim (TMP), whereas strains with cat1 or cmlA
      isolated from pigs often were resistant to DSM and TMP. Class 1 integrons were
      significantly more prevalent in strains with CP-resistance genes, compared with
      prevalence in strains without CP-resistance genes. All gene cassettes within the
      integrons were involved in resistance to DSM, TMP, or both. CONCLUSIONS AND
      CLINICAL RELEVANCE: Coresistance that develops because of the use of DSM and TMP
      in cattle and pigs apparently contributes to the selection of CP-resistant
      strains of E coli. Thus, it is possible that bacterial resistance to CP in
      animals would persist despite a ban on the use of CP in cattle and pigs.

PMID- 16454627
TI  - Evaluation of gait kinetics in puppies with coxofemoral joint laxity.
AB  - OBJECTIVE: To characterize ground reaction forces (GRFs) and determine whether
      there were correlations between forces and passive coxofemoral joint laxity in
      puppies. ANIMALS: Fifty-one 16-week-old hound-breed dogs. PROCEDURE: Force-plate
      gait evaluation and distraction radiographic imaging were performed. Ground
      reaction forces evaluated included x (mediolateral), y (craniocaudal breaking and
      propulsion), and z (vertical) peak force and impulse. Z-plane limb loading and
      unloading rates, loading interval, and weight distribution and y-plane stance
      time breaking and propulsion percentages were calculated. One-way ANOVA with the
      Duncan multiple range test was used to evaluate differences in gait variables
      among limbs. The relationships of left, right, highest, and mean distraction
      index (DI) with individual limb data of each dog were evaluated with the Spearman
      rank correlation. Left and right DIs were compared by means of linear regression
      analysis. RESULTS: Mean +/- SEM DI was 0.67 +/- 0.02. Left and right DIs were
      strongly correlated, but there were no significant relationships between DIs and
      gait variables. Most fore- and hind limb gait variables differed significantly,
      whereas paired fore- and hind limb gait variables did not. Asymmetry was most
      pronounced in the x- and y-planes. CONCLUSIONS AND CLINICAL RELEVANCE: GRFs were
      consistent with those of clinically normal mature dogs, supporting an absence of
      association between GRF and DI in young dogs. The GRFs and elucidation of the
      relationship between GRFs and DI may be useful for future studies in immature
      dogs.

PMID- 16454628
TI  - Development of a collagen-binding activity assay as a screening test for type II
      von Willebrand disease in dogs.
AB  - OBJECTIVE: To develop an assay to measure canine von Willebrand factor
      (vWF):collagen-binding activity (CBA) to screen for type 2 von Willebrand disease
      (vWD) in dogs. SAMPLE POPULATION: 293 plasma samples submitted for analysis of
      canine vWF antigen (vWF:Ag) and 12 control plasma samples from dogs with
      inherited type 2 or 3 vWD. PROCEDURE: Bovine collagens were evaluated for
      suitability as binding substrate for vWF. Assay sensitivity to depletion,
      proteolytic degradation, or a genetic deficiency of high-molecular-weight vWF
      were determined. Amounts of vWF:Ag and vWF:CBA were measured. The ratio of vWF:Ag
      to vWF:CBA was used to discriminate between type 1 and type 2 vWD. RESULTS: An
      assay for canine vWF activity was developed by use of mixed collagen (types I and
      III). When vWF:Ag was used to subtype vWD, 48% of the dogs were classified as
      clinically normal, 9% as indeterminate, and 43% as type 1 vWD. Inclusion of vWF
      activity resulted in reclassification of 5% of those identified as type 1 to type
      2 vWD. However, vWF:CBA of the reclassified dogs was not persistently abnormal, a
      finding compatible with acquired type 2 vWD. Some Doberman Pinschers had lower
      antigen-to-activity ratios than other breeds with type 1 vWD, suggesting that
      Doberman Pinschers have more functional circulating vWF. CONCLUSIONS AND CLINICAL
      RELEVANCE: Analysis of canine vWF activity should be included among the vWF
      specific assays used to confirm type 2 vWD. The prevalence of inherited forms of
      type 2 vWD in screened dogs is lower than acquired forms that can result
      secondary to underlying disease.

PMID- 16454629
TI  - Quantitative assessment of velocities of the annulus of the left atrioventricular
      valve and left ventricular free wall in healthy cats by use of two-dimensional
      color tissue Doppler imaging.
AB  - OBJECTIVE: To analyze velocities of the annulus of the left atrioventricular
      valve and left ventricular free wall (LVFW) in a large population of healthy cats
      by use of 2-dimensional color tissue Doppler imaging (TDI). ANIMALS: 100 healthy
      cats (0.3 to 12.0 years old; weighing 1.0 to 8.0 kg) of 6 breeds. PROCEDURE:
      Radial myocardial velocities were recorded in an endocardial and epicardial
      segment, and longitudinal velocities were recorded in 2 LVFW segments (basal and
      apical) and in the annulus of the left atrioventricular valve. RESULTS: LVFW
      velocities were significantly higher in the endocardial than epicardial layers
      and significantly higher in the basal than apical segments. For systole, early
      diastole, and late diastole, mean +/- SD radial myocardial velocity gradient
      (MVG), which was defined as the difference between endocardial and epicardial
      velocities, was 2.2 +/- 0.7, 3.3 +/- 1.3, and 1.8 +/- 0.7 cm/s, respectively, and
      longitudinal MVG, which was defined as the difference between basal and apical
      velocities, was 2.7 +/- 0.8, 3.1 +/- 1.4, and 2.1 +/- 0.9 cm/s, respectively. A
      breed effect was documented for several TDI variables; therefore, reference
      intervals for the TDI variables were determined for the 2 predominant breeds
      represented (Maine Coon and domestic shorthair cats). CONCLUSIONS AND CLINICAL
      RELEVANCE: LVFW velocities in healthy cats decrease from the endocardium to the
      epicardium and from the base to apex, thus defining radial and longitudinal MVG.
      These indices could complement conventional analysis of left ventricular function
      and contribute to the early accurate detection of cardiomyopathy in cats.

PMID- 16454630
TI  - Measurement of total thyroxine concentration in serum from dogs and cats by use
      of various methods.
AB  - OBJECTIVE: To compare results obtained from assay of total thyroxine (T4)
      concentration in serum of dogs and cats by use of 4 methods. SAMPLE POPULATION:
      Serum samples obtained from 98 dogs and 100 cats and submitted by veterinarians
      to an endocrine testing laboratory. PROCEDURE: Total T4 concentration was
      determined in each sample by use of 4 assay methods. Assay methods included a
      radioimmunoassay (RIA) marketed for use in dogs, an RIA for use in humans, a
      chemiluminescent enzyme immunoassay for use in humans, and an in-house ELISA.
      RESULTS: Total T4 concentrations obtained by use of all methods were
      significantly correlated. Bias-plot comparison revealed similar good overall
      agreement. Total T4 concentrations determined by use of the RIA marketed for use
      in dogs were generally lower than concentrations measured by use of the other
      methods. Clinical comparisons were made by evaluation of the T4 results in the
      context of the reference range recommended by each laboratory. A difference was
      found for clinical comparisons on the basis of T4 assay method when used to
      identify dogs as possible hypothyroid suspects. This difference was related more
      to the reference range used than to the absolute T4 value. The number of
      hyperthyroid-suspect cats with T4 values greater than the reference range was the
      same for each of the 4 assay methods. CONCLUSIONS AND CLINICAL RELEVANCE: Total
      T4 concentrations determined in dogs and cats by use of 4 commonly used methods
      provided similar and consistent results.

PMID- 16454631
TI  - Effects of administration of glucocorticoids and feeding status on plasma leptin
      concentrations in dogs.
AB  - OBJECTIVE: To investigate effects of short- and long- term administration of
      glucocorticoids, feeding status, and serum concentrations of insulin and cortisol
      on plasma leptin concentrations in dogs. ANIMALS: 20 nonobese dogs. PROCEDURE:
      For experiment 1, plasma leptin concentrations and serum concentrations of
      insulin and cortisol were monitored for 24 hours in 4 dogs administered
      dexamethasone (0.1 mg/kg, IV) or saline (0.9% NaCl) solution for fed and nonfed
      conditions. For experiment 2, 11 dogs were administered prednisolone (1 mg/kg,
      PO, q 24 h for 56 days [7 dogs] and 2 mg/kg, PO, q 24 h for 28 days [4 dogs]) and
      5 dogs served as control dogs. Plasma leptin and serum insulin concentrations
      were monitored weekly. RESULTS: For experiment 1, dexamethasone injection with
      the fed condition drastically increased plasma leptin concentrations.
      Furthermore, injection of saline solution with the fed condition increased plasma
      leptin concentrations. These increases in plasma leptin concentrations correlated
      with increases in serum insulin concentrations. Dexamethasone injection with the
      nonfed condition increased plasma leptin concentrations slightly but
      continuously. Injection of saline solution with the nonfed condition did not
      alter plasma leptin concentrations. For experiment 2, prednisolone administration
      at either dosage and duration did not alter plasma leptin concentrations in any
      dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dexamethasone injection and feeding
      increased plasma leptin concentrations in dogs. In addition, dexamethasone
      administration enhanced the effect of feeding on increases in plasma leptin
      concentrations. Daily oral administration of prednisolone (1 or 2 mg/kg) did not
      affect plasma leptin concentrations in dogs.

PMID- 16454632
TI  - Effect of microcurrent electrical tissue stimulation on equine tenocytes in
      culture.
AB  - OBJECTIVE: To determine effects of microcurrent electrical tissue stimulation
      (METS) on equine tenocytes cultured from the superficial digital flexor tendon
      (SDFT). SAMPLE POPULATION: SDFTs were collected from 20 horses at slaughter.
      PROCEDURE: Tenocytes were isolated following outgrowth from explants and grown in
      48-well plates. Four methods of delivering current to the tenocytes with a METS
      device were tested. Once the optimal method was selected, current consisting of 0
      (negative control), 0.05, 0.1, 0.5, 1.0, or 1.5 mA was applied to cells (8
      wells/current intensity) once daily for 8 minutes. Cells were treated for 1, 2,
      or 3 days. Cell proliferation, DNA content, protein content, and apoptosis rate
      were determined. RESULTS: Application of microcurrent of moderate intensity
      increased cell proliferation and DNA content, with greater increases with
      multiple versus single application. Application of microcurrent of moderate
      intensity once or twice increased protein content, but application 3 times
      decreased protein content. Application of current a single time did not
      significantly alter apoptosis rate; however, application twice or 3 times
      resulted in significant increases in apoptosis rate, and there were significant
      linear (second order) correlations between current intensity and apoptosis rate
      when current was applied twice or 3 times. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results of the present study indicate that microcurrent affects the behavior of
      equine tenocytes in culture, but that effects may be negative or positive
      depending on current intensity and number of applications. Therefore, results are
      far from conclusive with respect to the suitability of using METS to promote
      tendon healing in horses.

PMID- 16454633
TI  - Evaluation of a pressure walkway system for measurement of vertical limb forces
      in clinically normal dogs.
AB  - OBJECTIVE: To compare ground reaction forces (GRFs) measured by use of a pressure
      sensitive walk-way (PSW) and a force plate (FP) and evaluate weekly variation in
      the GRFs and static vertical forces in dogs. ANIMALS: 34 clinically normal dogs
      and 5 research dogs with lameness. PROCEDURE: GRF data were collected from 5 lame
      and 14 clinically normal dogs by use of an FP and a PSW. Peak vertical force
      (PVF), vertical impulse (VI), and velocity measurements (determined by use of
      photocells and PSW data) were compared between groups. Peak vertical force, VI,
      stride length, ground phase time (ie, contact time), and static body weight
      distribution data were collected on 2 occasions, 1 week apart, in 20 different
      clinically normal dogs by use of a PSW; week-to-week variation in values was
      evaluated. RESULTS: Measurements of velocity derived by use of the photocells
      were not different from those derived by use of the PSW. For any 1 limb, values
      derived by use of the PSW were significantly lower than values derived with the
      FP. For values obtained by use of either technique, there were no differences
      between left and right limbs except for values of PVF measured via PSW in
      forelimbs. Values of PVF, VI, contact time, stride length, and static weight
      distribution generated by the PSW did not vary from week to week. CONCLUSIONS AND
      CLINICAL RELEVANCE: Values for GRFs varied between the FP and PSW. However, data
      derived by use of PSW were consistent and could be used to evaluate kinetic
      variables over time in the same dog.

PMID- 16454634
TI  - Matrix metalloproteinase-9 activity in the cerebrospinal fluid and serum of dogs
      with acute spinal cord trauma from intervertebral disk disease.
AB  - OBJECTIVE: To detect matrix metalloproteinase (MMP)-9 in serum and CSF and
      determine relationships between MMP activity and severity of disease, duration of
      clinical signs, and duration of hospitalization in dogs with acute intervertebral
      disk disease (IVDD). ANIMALS: 35 dogs with acute IVDD and 8 clinically normal
      control dogs. PROCEDURE: CSF and serum were collected from affected and control
      dogs. Zymography was used to detect MMP-9. RESULTS: Activity of MMP-9 in CSF was
      detected in 6 of 35 dogs with IVDD; activity was significantly more common in
      dogs with duration of signs < 24 hours. Paraplegic dogs were more likely to have
      MMP-9 activity in the CSF than non-paraplegic dogs. No significant difference in
      hospitalization time was detected in dogs with IVDD between those with and
      without activity of MMP-9 in the CSF. Serum MMP-9 was detected more frequently in
      dogs with IVDD than in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Data
      were consistent with results of experimental rodent spinal cord injury studies
      that indicate that MMP-9 is expressed early during secondary injury.

PMID- 16454635
TI  - Evaluation of acoustic wave propagation velocities in the ocular lens and
      vitreous tissues of pigs, dogs, and rabbits.
AB  - OBJECTIVE: To evaluate propagation velocity of acoustic waves through the lens
      and vitreous body of pigs, dogs, and rabbits and determine whether there were
      associations between acoustic wave speed and age, temperature, and time after
      enucleation. SAMPLE POPULATION: 9 pig, 40 dog, and 20 rabbit lenses and 16 pig,
      17 dog, and 23 rabbit vitreous bodies. PROCEDURE: Acoustic wave velocities
      through the ocular structures were measured by use of the substitution technique.
      RESULTS: Mean sound wave velocities in lenses of pigs, dogs, and rabbits were
      1,681, 1,707, and 1,731 m/s, respectively, at 36 degrees C. Mean sound wave
      velocities in the vitreous body of pigs, dogs, and rabbits were 1,535, 1,535, and
      1,534 m/s, respectively, at 38 degrees C. The sound wave speed through the
      vitreous humor, but not the lens, increased linearly with temperature. An
      association between wave speed and age was observed in the rabbit tissues. Time
      after enucleation did not affect the velocity of sound in the lens or vitreous
      body. The sound wave speed conversion factors for lenses, calculated with respect
      to human ocular tissue at 36 degrees C, were 1.024, 1.040, and 1.055 for pig,
      dog, and rabbit lenses, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      Conversion factors for the speed of sound through lens tissues are needed to
      avoid underestimation of the thickness of the lens and axial length of the eye in
      dogs during comparative A-mode ultrasound examinations. These findings are
      important for accurate calculation of intraocular lens power required to achieve
      emmetropia in veterinary patients after surgical lens extraction.

PMID- 16454636
TI  - Evaluation of concentration of voriconazole in aqueous humor after topical and
      oral administration in horses.
AB  - OBJECTIVE: To determine penetration of topically and orally administered
      voriconazole into ocular tissues and evaluate concentrations of the drug in blood
      and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy
      adult horses. PROCEDURE: Each eye in 6 horses was treated with a single
      concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole
      solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed
      and plasma samples were collected after application of the final dose.
      Voriconazole concentrations in aqueous humor (AH) and plasma were measured via
      high-performance liquid chromatography. Five horses received a single orally
      administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was
      performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/-
      SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%,
      and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37
      microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively.
      The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations
      than the 0.5% solution, and only the 3.0% solution induced signs of ocular
      toxicosis. Voriconazole was detected in the plasma for 1 hour after the final
      topically administered dose of all solutions. Mean +/- SD voriconazole
      concentration in AH after a single orally administered dose was 0.86 +/- 0.22
      microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that
      voriconazole effectively penetrated the cornea in clinically normal eyes and
      reached detectable concentrations in the AH after topical administration. The
      drug also penetrated noninflamed equine eyes after oral administration. Low
      plasma concentrations of voriconazole were detected after topical administration.

PMID- 16454637
TI  - Assessment of glutamate loss from the ganglion cell layer of young DBA/2J mice
      with glaucoma.
AB  - OBJECTIVE: To determine whether glutamate contents are decreased in the ganglion
      cell layer (GCL) of retinas of DBA/2J mice with glaucoma, compared with
      unaffected control mice. SAMPLE POPULATION: 20 eyes from DBA/2J mice (9-week-old
      mice [n = 8] and 4- [4], 6- [4], and 12-month-old [4] mice) and 17 eyes from
      control CD-1 (7) and C57/BL6 (10) mice of similar age. PROCEDURE: After
      euthanasia, the eyes were rapidly dissected and fixed. Serial 0.5-microm sections
      were prepared from eyecups and stained with toluidine blue (to identify damaged
      cells) or immunogold (to localize glutamate). Microscopic images were captured
      digitally for comparison; immunostaining densities were assessed via special
      software. RESULTS: In the GCL of control mice, few cells appeared damaged; large
      amounts of glutamate were detected in 83 +/- 8.3% of cells. In DBA/2J mice > or =
      9 weeks of age, damaged neurons were observed in retinal sections; the level of
      glutamate immunoreactivity was high in a few cells near areas of damage (13 +/-
      3.2%) and in many cells in less-damaged regions of the same sections (82 +/-
      4.2%). Many neurons with low amounts of glutamate in damaged regions did not
      appear damaged histologically. CONCLUSIONS AND CLINICAL RELEVANCE: In retinas of
      young DBA/2J mice, damaged and undamaged GCL cells had decreased levels of
      immunostaining for glutamate, compared with less-damaged adjacent regions or
      retinas from control mice. The loss of neuronal glutamate in damaged retinal
      regions suggests that glutamate is contributing to early retinal damage prior to
      changes in intraocular pressure.

PMID- 16454638
TI  - Pharmacokinetics and tissue distribution of doxycycline after oral administration
      of single and multiple doses in horses.
AB  - OBJECTIVE: To determine pharmacokinetics, safety, and penetration into
      interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor
      of doxycycline after oral administration of single and multiple doses in horses.
      ANIMALS: 6 adult horses. PROCEDURE: The effect of feeding on drug absorption was
      determined. Plasma samples were obtained after administration of single or
      multiple doses of doxycycline (20 mg/kg) via nasogastric tube. Additionally, ISF,
      PMNLs, and aqueous humor samples were obtained after the final administration.
      Horses were monitored for adverse reactions. RESULTS: Feeding decreased drug
      absorption. After multiple doses, mean +/- SD time to maximum concentration was
      1.63 +/- 1.36 hours, maximum concentration was 1.74 +/- 0.3 microg/mL, and
      elimination half-life was 12.07 +/- 3.17 hours. Plasma protein binding was 81.76
      +/- 2.43%. The ISF concentrations correlated with the calculated percentage of
      non-protein-bound drug. Maximum concentration was 17.27 +/- 8.98 times as great
      in PMNLs, compared with plasma. Drug was detected in aqueous humor at 7.5% to 10%
      of plasma concentrations. One horse developed signs of acute colitis and required
      euthanasia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that doxycycline
      administered at a dosage of 20 mg/kg, PO, every 24 hours will result in drug
      concentrations adequate for killing intracellular bacteria and bacteria with
      minimum inhibitory concentration < or = 0.25 microg/mL. For bacteria with minimum
      inhibitory concentration of 0.5 to 1.0 microg/mL, a dosage of 20 mg/kg, PO, every
      12 hours may be required; extreme caution should be exercised with the higher
      dosage until more safety data are available.

PMID- 16454639
TI  - Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine
      after intravenous infusion in anesthetized horses.
AB  - OBJECTIVE: To determine the disposition of lidocaine after IV infusion in
      anesthetized horses undergoing exploratory laparotomy because of gastrointestinal
      tract disease. ANIMALS: 11 horses (mean +/- SD, 10.3 +/- 7.4 years; 526 +/- 40
      kg). PROCEDURE: Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15
      minute period [87.5 microg/kg/min]; maintenance infusion, 50 microg/kg/min for 60
      to 90 minutes) was administered IV to dorsally recumbent anesthetized horses.
      Blood samples were collected before and at fixed time points during and after
      lidocaine infusion for analysis of serum drug concentrations by use of liquid
      chromatography-mass spectrometry. Serum lidocaine concentrations were evaluated
      by use of standard noncompartmental analysis. Selected cardiopulmonary variables,
      including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and
      PaO2, were recorded. Recovery quality was assessed and recorded. RESULTS: Serum
      lidocaine concentrations paralleled administration, increasing rapidly with the
      initiation of the loading infusion and decreasing rapidly following
      discontinuation of the maintenance infusion. Mean +/- SD volume of distribution
      at steady state, total body clearance, and terminal half-life were 0.70 +/- 0.39
      L/kg, 25 +/- 3 mL/kg/min, and 65 +/- 33 minutes, respectively. Cardiopulmonary
      variables were within reference ranges for horses anesthetized with inhalation
      anesthetics. Mean HR ranged from 36 +/- 1 beats/min to 43 +/- 9 beats/min, and
      mean MAP ranged from 74 +/- 18 mm Hg to 89 +/- 10 mm Hg. Recovery quality ranged
      from poor to excellent. CONCLUSIONS AND CLINICAL RELEVANCE: Availability of
      pharmacokinetic data for horses with gastrointestinal tract disease will
      facilitate appropriate clinical dosing of lidocaine.

PMID- 16454640
TI  - Pharmacokinetics of a novel formulation of ivermectin after administration to
      goats.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of a novel commercial formulation of
      ivermectin after administration to goats. ANIMALS: 6 healthy adult goats.
      PROCEDURE: Ivermectin (200 microg/kg) was initially administered IV to each goat,
      and plasma samples were obtained for 36 days. After a washout period of 3 weeks,
      each goat received a novel commercial formulation of ivermectin (200 microg/kg)
      by SC injection. Plasma samples were then obtained for 42 days. Drug
      concentrations were quantified by use of high-performance liquid chromatography
      with fluorescence detection. RESULTS: Pharmacokinetics of ivermectin after IV
      administration were best described by a 2-compartment open model; values for main
      compartmental variables included volume of distribution at a steady state (9.94
      L/kg), clearance (1.54 L/kg/d), and area under the plasma concentration-time
      curve (AUC; 143 [ng x d]/mL). Values for the noncompartmental variables included
      mean residence time (7.37 days), AUC (153 [ng x d]/mL), and clearance (1.43
      L/kg/d). After SC administration, noncompartmental pharmacokinetic analysis was
      conducted. Values of the variables calculated by use of this method included
      maximum plasma concentration (Cmax; 21.8 ng/mL), time to reach Cmax (3 days), and
      bioavailability (F; 91.8%). CONCLUSIONS AND CLINICAL RELEVANCE: The commercial
      formulation used in this study is a good option to consider when administering
      ivermectin to goats because of the high absorption, which is characterized by
      high values of F. In addition, the values of Cmax and time to reach Cmax are
      higher than those reported by other investigators who used other routes of
      administration.

PMID- 16454641
TI  - Effect of oral administration of clinically relevant doses of dexamethasone on
      regulation of cytochrome P450 subfamilies in hepatic microsomes from dogs and
      rats.
AB  - OBJECTIVE: To evaluate the effect of oral administration of dexamethasone (DEX)
      at clinically relevant doses on metabolic activities of cytochrome P450 (CYP)
      isoenzymes in dogs and rats. ANIMALS: 15 healthy 1-year-old male Beagles and 20
      healthy 10-week-old male Wistar rats. PROCEDURE: Hepatic microsomes were
      harvested from dogs treated orally with DEX at 2.5 and 7.5 mg for 5 days and from
      rats treated orally with DEX at 0.75, 6, and 48 mg/kg for 5 days. 7
      ethoxyresorufin, tolbutamide, bufuralol, and midazolam were used as CYP1A, CYP2C,
      CYP2D, and CYP3A substrates, respectively. Concentrations of metabolites formed
      by CYPs were measured by use of high-performance liquid chromatography, except
      for the resorufin concentrations measured by use of a fluorometric method.
      Reaction velocity-substrate concentration data were analyzed to obtain maximum
      reaction velocity (Vmax) and Michaelis-Menten constant (Km). RESULTS: Values of
      Vmax for midazolam 4-hydroxylation were significantly decreased by treatment with
      DEX at 2.5 and 7.5 mg in dogs, although values of Km were not affected. Values of
      Vmax for bufuralol 1'-hydroxylation were also decreased by treatment with DEX. In
      rats, values of Vmax for midazolam 4- hydroxylation were significantly decreased
      by treatment with DEX at 0.75 and 6 mg/kg but significantly increased at 48
      mg/kg. Other reactions were not affected by treatment with DEX. CONCLUSIONS AND
      CLINICAL RELEVANCE: Our results indicate that DEX downregulates the CYP3A
      subfamily when administered at clinically relevant doses to dogs. The effect of
      downregulation of CYP3A in dogs treated with DEX should be considered to avoid
      adverse effects from coadministration of drugs.

PMID- 16454643
TI  - Evaluation of association between body size and large intestinal transit time in
      healthy dogs.
AB  - OBJECTIVE: To compare large intestinal transit time (LITT) in dogs of various
      body sizes and determine whether fecal quality was correlated with LITT. ANIMALS:
      6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great
      Danes. PROCEDURE: LITT was calculated as the difference between total (TTT) and
      orocecal transit time (OCTT). Minimum and mean OCTTs were determined by use of
      the sulfasalazine-sulfapyridine method. Minimum TTT was estimated by use of
      chromium and ferric oxide as color markers, and mean TTT was calculated from the
      recovery from feces of ingested colored plastic beads. Fecal moisture content was
      determined and fecal consistency was scored during the same period. RESULTS:
      Large-breed dogs had higher fecal moisture content and more watery fecal
      consistency. No association between body size and OCTT was detected, but there
      was a positive correlation between body size and mean TTT. Mean LITT increased
      significantly with body size, from 9.1 +/- 1.1 hours in Miniature Poodles to 39.4
      +/- 1.6 hours for Giant Schnauzers. Significant correlations were detected among
      mean LITT, mean TTT, and fecal scores, whereas no correlation was observed
      between fecal moisture content and TTT or LITT. CONCLUSIONS AND CLINICAL
      RELEVANCE: LITT was correlated with fecal consistency in dogs of various body
      sizes. Mean LITT can be predicted from values for mean TTT in healthy dogs.

PMID- 16454642
TI  - Blood lipid concentrations and lipoprotein patterns in captive and wild American
      black bears (Ursus americanus).
AB  - OBJECTIVE: To compare blood lipid concentrations and lipoprotein patterns for
      captive and wild American black bears (Ursus americanus). ANIMALS: 7 captive and
      9 wild adult (> or = 4 years old) black bears. PROCEDURE: Blood was collected
      from 2 groups of captive black bears (groups A and B) and 1 group of wild black
      bears (group C). Blood triglyceride (TG) and cholesterol concentrations were
      compared among groups. Plasma lipoproteins were isolated by use of a self
      generating gradient of iodixanol, and lipoprotein patterns were compared between
      groups A and B. RESULTS: Captive bears (mean +/- SD, 187.8 +/- 44.4 kg) weighed
      significantly more than wild bears (mean, 104.8 +/- 41.4 kg), but mean body
      weight did not differ between groups A and B. Mean blood TG concentrations for
      groups B (216.8 +/- 16.0 mg/dL) and C (190.7 +/- 34.0 mg/dL) were significantly
      higher than that of group A (103.9 +/- 25.3 mg/dL). Mean blood cholesterol
      concentration was also significantly higher for group B (227.8 +/- 8.2 mg/dL)
      than for groups A (171.7 +/- 35.5 mg/dL) or C (190.8 +/- 26.8 mg/dL). Mean very
      low-density lipoprotein TG and low-density lipoprotein cholesterol concentrations
      were 2- and 3-fold higher, respectively, for group B, compared with
      concentrations for group A. CONCLUSIONS AND CLINICAL RELEVANCE: Blood lipid
      concentrations vary significantly among populations of black bears. Plasma
      lipoprotein patterns of captive bears differed significantly between colonies and
      may have reflected differences in diet or management practices.

PMID- 16454644
TI  - Immunohistochemical determination of the expression of endothelin receptors in
      bronchial smooth muscle and epithelium of healthy horses and horses affected by
      summer pasture-associated obstructive pulmonary disease.
AB  - OBJECTIVE: To immunohistochemically determine the expression of endothelin (ET)
      receptors in bronchial smooth muscle and epithelium of healthy horses and horses
      affected by summer pasture-associated obstructive pulmonary disease (SPAOPD).
      SAMPLE POPULATION: Tissue specimens obtained from 8 healthy and 8 SPAOPD-affected
      horses. PROCEDURE: Horses were examined and assigned to healthy and SPAOPD
      groups. Horses were then euthanatized, and tissue specimens containing bronchi of
      approximately 4 to 8 mm in diameter were immediately collected from all lung
      lobes, fixed in zinc-formalin solution for 12 hours, and embedded in paraffin.
      Polyclonal primary antibodies against ET-A or ET-B receptors at a dilution of
      1:200 and biotinylated IgG secondary antibodies were applied to tissue sections,
      followed by the addition of an avidin-biotin immunoperoxidase complex.
      Photographs of the stained slides were digitally recorded and analyzed by use of
      image analysis software to determine the intensity of staining. Two-way ANOVA was
      used for statistical analysis. RESULTS: The left diaphragmatic lung lobe of
      SPAOPD-affected horses had a significantly greater area of bronchial smooth
      muscle that immunostained for ET-A, compared with that for healthy horses. All
      lung lobes of SPAOPD-affected horses, except for the right diaphragmatic lobe,
      had significantly greater staining for ET-B receptors in bronchial smooth muscle,
      compared with results for healthy horses. CONCLUSIONS AND CLINICAL RELEVANCE:
      This study revealed overexpression of ET-A and, in particular, ETB receptors in
      the bronchial smooth muscle of SPAOPD-affected horses, which suggested
      upregulation of these receptors. These findings improve our understanding of the
      role of ET-1 in the pathogenesis of SPAOPD.

PMID- 16454645
TI  - Evaluation of Coomassie blue staining of the acrosome of equine and canine
      spermatozoa.
AB  - OBJECTIVE: To evaluate Coomassie blue staining of the acrosome of equine and
      canine spermatozoa. SAMPLE POPULATION: Spermatozoa of 5 mixed-breed male dogs and
      3 Thoroughbred stallions. PROCEDURE: Various proportions of intact and acrosome
      damaged spermatozoa were fixed in 2% phosphate-buffered formaldehyde or 4%
      paraformaldehyde, smeared onto glass slides, and stained with Coomassie blue
      stain. Acrosomal status (damaged vs intact) was also assessed by use of flow
      cytometry after staining with fluorescein isothiocyanate-conjugated Pisum sativum
      agglutinin (FITC-PSA) and propidium iodide. Comparisons were made between
      percentages of expected and observed acrosome-intact spermatozoa in different
      proportions of live and flash-frozen samples; the percentages of acrosome-intact
      spermatozoa as determined by use of Coomassie blue staining and flow cytometry
      were also compared. RESULTS: Strong correlations were found between the expected
      and observed distributions of acrosome-intact spermatozoa when fixed in 4%
      paraformaldehyde (r2 = 0.93 and 0.89 for canine and equine spermatozoa,
      respectively) as well as between Coomassie blue-stained cells and those stained
      with FITC-PSA and assessed by use of flow cytometry (r2 = 0.96 and 0.97 for
      canine and equine spermatozoa, respectively). However, in canine samples that
      were fixed in 2% phosphate-buffered formaldehyde, these correlations were weak.
      CONCLUSIONS AND CLINICAL RELEVANCE: Staining with Coomassie blue stain was a
      simple and accurate method to evaluate the acrosome in equine and canine
      spermatozoa after fixation in 4% paraformaldehyde. This assay should be useful in
      routine evaluation of semen samples from these species.

PMID- 16454646
TI  - Assessment of ruminal degradation, oral bioavailability, and toxic effects of
      anticoagulant rodenticides in sheep.
AB  - OBJECTIVE: To assess the rate and extent of ruminal degradation of warfarin,
      chlorophacinone, and bromadiolone in vitro and determine the oral availability
      and clinical and hemostatic effects of each anticoagulant rodenticide in adult
      sheep. ANIMALS: 3 Texel sheep. PROCEDURE: Samples of ruminal fluid were incubated
      with each of the anticoagulants to assess the kinetics of ruminal degradation
      over 24 hours. To determine the plasma kinetics of the anticoagulants, each sheep
      received each of the anticoagulants IV or via a rumenimplanted cannula at 2-month
      intervals (3 rodenticide exposures/sheep). At intervals during a 240- to 360-
      hour period after treatment, prothrombin time (PT) was measured, plasma
      anticoagulant concentration was assessed, and clinical signs of rodenticide
      poisoning were monitored. In plasma and rumen extracts, anticoagulant
      concentrations were determined via high-performance liquid chromatography.
      RESULTS: In the rumen extracts, anticoagulants were slightly degraded (< 15%)
      over 24 hours. In vivo, oral availability of warfarin, chlorophacinone, and
      bromadiolone was estimated at 79%, 92%, and 88%, respectively. Although maximum
      PT was 80 seconds after chlorophacinone and bromadiolone treatments, no clinical
      signs of toxicosis were detected; PT returned to baseline values within 2 weeks.
      CONCLUSIONS AND CLINICAL RELEVANCE: In sheep, warfarin, chlorophacinone, and
      bromadiolone were not degraded in the rumen but their bioavailabilities were high
      after oral administration; the kinetics of these compounds in sheep and other
      mammals are quite similar. These data suggest that the lack of susceptibility of
      ruminants to these anticoagulant rodenticides cannot be explained by either
      ruminal degradation or the specific toxicokinetics of these anticoagulants.

PMID- 16454647
TI  - Natural killer cell-mediated rejection of experimental human lung cancer by
      genetic overexpression of major histocompatibility complex class I chain-related
      gene A.
AB  - Studies have highlighted molecular and cell biological mechanisms of the NKG2D
      NKG2D ligand system in the activation of natural killer (NK) cell and T cell
      functions. In this study we explore the potential of genetic overexpression of
      human major histocompatibility complex class I chain-related gene A (MICA), a
      powerful NKG2D ligand, for the induction of NK cell-mediated antitumor immunity
      in a humanized murine model of non-small cell lung cancer. Using tissue
      microarray technology we detected expression of MICA in only 30% of the samples
      from patients with lung cancer. Staining was always weak and focal, indicating
      that expression of MICA is detectable but limited in human lung cancer. Genetic
      overexpression of MICA by means of adenoviral transduction or transfection of
      expression plasmids was feasible in cell lines in vitro, primary human cancer
      tissue ex vivo, and in experimental human cancers in vivo. The presence of MICA
      on the surface of largely NK cell-resistant human lung cancer cells reestablished
      NK cell susceptibility and provoked NK cell-mediated antitumor immunity by murine
      and human NK cells in two different experimental therapy models. In this study we
      analyze the interaction of human NK cells with MICA-positive human cancer cells
      in an in vivo setting. Our data demonstrate that MICA overexpression can function
      as NK cell-mediated immunotherapy in experimental lung cancer.

PMID- 16454649
TI  - In vitro functional correction of the mutation responsible for murine severe
      combined immune deficiency by small fragment homologous replacement.
AB  - A homologous recombination (HR) approach for site-specific correction of
      mutations would be highly desirable for the treatment of genetic disorders if
      recombination efficiencies were sufficiently high as to permit a biological
      effect. Using a T cell thymoma line derived from severe combined immunodeficient
      (SCID) mice with a point mutation in the gene encoding the DNA-dependent protein
      kinase catalytic subunit (DNA-PKcs), we have shown that short DNA fragments
      (SDFs; 621 bases) can provide genotypic and functional correction of these cells.
      Double-stranded SDFs (dsSDFs) or single-stranded SDFs (ssSDFs) were designed to
      span the wild-type sequence of exon 85 in the DNA-PKcs gene and part of the 3'
      and 5' flanking intron regions. SCID cells were nucleofected with both single-
      and double-stranded wild-type SDF sequences. Corrected cells were selected on the
      basis of protection from radiation hypersensitivity that occurs as a consequence
      of the SCID mutation. Correction was mediated by both SDF forms (double and
      single stranded). These results indicate that SDFs can correct point mutations by
      HR with the possibility of harnessing ionizing radiation (IR) as a selection
      method to eliminate noncorrected cells and enrich for corrected SCID
      radioresistant cells.

PMID- 16454648
TI  - Diffusible VP22-E2 protein kills bystander cells and offers a route for cervical
      cancer gene therapy.
AB  - Human papillomaviruses (HPVs) are a causative agent of cervical cancer and are
      implicated in several other types of malignant disease including cancer of the
      vulva, oral cancer, and skin cancer. In HPV-transformed cells, expression of the
      viral E6 and E7 oncogenes increases cell proliferation and inhibits apoptosis.
      Expression of the viral E2 protein in HPV-transformed cells represses
      transcription of E6 and E7 and induces apoptosis and/or growth arrest. We have
      shown previously that herpes simplex virus type 1 (HSV-1) VP22-HPV E2 fusion
      proteins can traffic between cells and induce apoptosis. Here we show that
      replication-defective adenoviruses can be used to deliver VP22-E2 fusion proteins
      to target cells. We show that the use of adenoviral vectors to deliver VP22-E2
      proteins leads to high levels of apoptosis. Interestingly, VP22-E2 proteins
      produced in adenovirus-infected cells are able to enter uninfected cells and
      induce apoptosis. Trafficking between cells and the induction of apoptosis in
      bystander cells are detectable in a three-dimensional tumor model. These results
      suggest that adenoviral vectors expressing VP22-E2 fusion proteins could be used
      to treat cervical cancer and other HPV-associated diseases.

PMID- 16454650
TI  - Adenoviral vector-delivered pigment epithelium-derived factor for neovascular age
      related macular degeneration: results of a phase I clinical trial.
AB  - Twenty-eight patients with advanced neovascular age-related macular degeneration
      (AMD) were given a single intravitreous injection of an E1-, partial E3-, E4
      deleted adenoviral vector expressing human pigment epithelium- derived factor
      (AdPEDF.11). Doses ranging from 10(6) to 10(9.5) particle units (PU) were
      investigated. There were no serious adverse events related to AdPEDF.11 and no
      dose-limiting toxicities. Signs of mild, transient intraocular inflammation
      occurred in 25% of patients, but there was no severe inflammation. Six patients
      experienced increased intraocular pressure that was easily controlled by topical
      medication. All adenoviral cultures were negative. At 3 and 6 months after
      injection, 55 and 50%, respectively, of patients treated with 10(6)-10(7.5) PU
      and 94 and 71% of patients treated with 10(8)-10(9.5) PU had no change or
      improvement in lesion size from baseline. The median increase in lesion size at 6
      and 12 months was 0.5 and 1.0 disk areas in the low-dose group compared with 0
      and 0 disk areas in the high-dose group. These data suggest the possibility of
      antiangiogenic activity that may last for several months after a single
      intravitreous injection of doses greater than 10(8) PU of AdPEDF.11. This study
      provides evidence that adenoviral vector-mediated ocular gene transfer is a
      viable approach for the treatment of ocular disorders and that further studies
      investigating the efficacy of AdPEDF.11 in patients with neovascular AMD should
      be performed.

PMID- 16454651
TI  - Commentary: an aye for eye gene therapy.

PMID- 16454652
TI  - Nerve growth factor improves the muscle regeneration capacity of muscle stem
      cells in dystrophic muscle.
AB  - Researchers have attempted to use gene- and cell-based therapies to restore
      dystrophin and alleviate the muscle weakness that results from Duchenne muscular
      dystrophy (DMD). Our research group has isolated populations of muscle-derived
      stem cells (MDSCs) from the postnatal skeletal muscle of mice. In comparison with
      satellite cells, MDSCs display an improved transplantation capacity in dystrophic
      mdx muscle that we attribute to their ability to undergo long-term proliferation,
      self-renewal, and multipotent differentiation, including differentiation toward
      endothelial and neuronal lineages. Here we tested whether the use of nerve growth
      factor (NGF) improves the transplantation efficiency of MDSCs. We used two
      methods of in vitro NGF stimulation: retroviral transduction of MDSCs with a CL
      NGF vector and direct stimulation of MDSCs with NGF protein. Neither method of
      NGF treatment changed the marker profile or proliferation behavior of the MDSCs,
      but direct stimulation with NGF protein significantly reduced the in vitro
      differentiation ability of the cells. NGF stimulation also significantly enhanced
      the engraftment efficiency of MDSCs transplanted within the dystrophic muscle of
      mdx mice, resulting in the regeneration of numerous dystrophin-positive muscle
      fibers. These findings highlight the importance of NGF as a modulatory molecule,
      the study of which will broaden our understanding of its biologic role in the
      regeneration and repair of skeletal muscle by musclederived cells.

PMID- 16454653
TI  - Adenovirus vectors based on human adenovirus type 19a have high potential for
      human muscle-directed gene therapy.
AB  - Until recently, adenovirus-based gene therapy has been almost exclusively based
      on human adenovirus serotype 5 (Ad5). The aim of this study was to systematically
      compare the efficiency of transduction of primary muscle cells from various
      species by two adenoviral vectors from subgroups C and D. Transduction of a panel
      of myoblasts demonstrated a striking specificity of an Ad19a-based replication
      defective E1-deleted vector (Ad19aEGFP) for human cells, whereas the Ad5-based
      vector had high affinity for nonhuman primate myoblasts. Transgene expression
      correlated well with cell-associated vector genomes. Up to 6.59% of the initially
      applied Ad19aEGFP vector particles were taken up by human myoblasts, as compared
      with 0.1% of the corresponding Ad5 vector. Remarkably, Ad19aEGFP but not Ad5EGFP
      efficiently transduced differentiated human myotubes, an in vitro model for
      skeletal muscle transduction. Uptake of Ad19aEGFP vector particles in human
      myotubes was 12-fold more efficient than that of Ad5EGFP. Moreover, both vectors
      demonstrated an early block at the level of vector uptake in mouse myoblasts and
      rat L6 cells. Investigation of the underlying mechanism for binding and uptake of
      the two vectors by human myoblasts showed high susceptibility for Ad19a to
      neuraminidase and wheat germ agglutinin (WGA) lectin, whereas Ad5-mediated
      transduction was dependent on binding to the coxsackie-adenovirus receptor (CAR)
      and sensitive to soluble RGD peptide and heparin. Our study offers insights into
      species-dependent factors that determine Ad tropism and, moreover, provides a
      basis for application of the novel Ad19a-based vector for gene transfer into
      human skeletal muscle.

PMID- 16454654
TI  - Kallikrein protects against ischemic stroke by inhibiting apoptosis and
      inflammation and promoting angiogenesis and neurogenesis.
AB  - Stroke-induced neurological deficits and mortality are often associated with
      timing of treatment after the onset of stroke. We showed that local delivery of
      the human tissue kallikrein gene into rat brain immediately after middle cerebral
      artery occlusion (MCAO) exerts neuroprotection. In this study, we investigated
      the effect of systemic delivery of the kallikrein gene 8 hr after MCAO.
      Expression of recombinant human tissue kallikrein after gene transfer was
      identified in the ischemic brain region and blood vessels. Intravenous injection
      of adenovirus encoding the kallikrein gene significantly reduced neurological
      deficit scores 2 and 7 days after gene transfer. Kallikrein gene transfer also
      reduced ischemia-reperfusion (I/R)-induced cerebral infarction and promoted the
      survival and migration of glial cells from penumbra to the ischemic core from 3
      to 14 days after gene delivery. Kallikrein reduced I/R-induced apoptosis of
      neuronal cells and inhibited inflammatory cell accumulation in the ischemic
      brain. These effects were blocked by the kinin B2 receptor antagonist icatibant.
      In addition, kallikrein enhanced angiogenesis and promoted neurogenesis after I/R
      and the stimulatory effect of kinin on neuronal cell proliferation was confirmed
      in primary cultured neuronal cells. The protective effects of kallikrein, through
      the kinin B2 receptor, were accompanied by increased cerebral nitric oxide and
      Bcl-2 levels, Akt phosphorylation, and reduced NAD(P)H oxidase activity,
      superoxide production, Bax levels, and caspase-3 activity. These results indicate
      that delayed systemic administration of the kallikrein gene after onset of stroke
      protects against ischemic brain injury by inhibiting apoptosis and inflammation
      and by promoting angiogenesis and neurogenesis.

PMID- 16454655
TI  - Clinical protocol: phase I study of an adenovirus/prostate-specific antigen
      vaccine in men with metastatic prostate cancer.

PMID- 16454656
TI  - Intracoronary delivery of an adenovirus encoding fibroblast growth factor-4 in
      myocardial ischemia: effect of serum antibodies and previous exposure to
      adenovirus.
AB  - The presence of anti-adenoviral serotype 5 (Ad5) antibodies may limit the
      efficacy of Ad5-mediated gene transfer. We therefore tested the hypothesis that
      intracoronary delivery of an adenovirus encoding human fibroblast growth factor
      type 4 (Ad5.FGF4) would improve regional myocardial function in an animal model
      of ischemia when high antibody levels preexist or after a prior intracoronary
      dose of Ad5. High anti-Ad5 antibody levels were generated in pigs by subcutaneous
      immunization with an adenovirus encoding LacZ (Ad5.lacZ). Neutralizing antibody
      levels increased 648-fold (range, 82- to 2108-fold) above preimmunization levels,
      and persisted for the duration of the study. Myocardial function during pacing
      induced ischemia was improved in the ischemic region (p<0.001) at both 2 and 4
      weeks after Ad5.FGF4 administration despite the presence of preexisting
      antibodies to Ad5. In a second set of experiments, the efficacy of a second
      intracoronary administration of Ad5 was determined by exposing the animals first
      to an intracoronary dose of Ad5.lacZ, followed 7 weeks later by the therapeutic
      dose of Ad5.FGF4. After delivery of Ad5.lacZ, anti-Ad5 antibody levels increased
      8-fold (range, 1- to 18-fold), but this prior exposure to Ad5 did not prevent the
      therapeutic effects after subsequent intracoronary dosing with Ad5.FGF4
      (p<0.001). In the porcine Ameroid constrictor model of myocardial ischemia the
      presence of anti-Ad5 antibodies or prior intracoronary dosing with adenovirus
      does not prevent the ability of Ad5.FGF4, delivered by intracoronary injection,
      from normalizing regional myocardial function.

PMID- 16454657
TI  - Local delivery of vaccinia virus expressing multiple costimulatory molecules for
      the treatment of established tumors.
AB  - Successful immunotherapy of established tumors depends on overcoming the
      suppressive influence of the local tumor microenvironment. The direct injection
      of vaccinia virus expressing the B7.1 (CD80) costimulatory molecule into melanoma
      lesions resulted in local and systemic immunity with associated clinical
      responses. Therefore, we sought to evaluate the effects of a vaccinia virus
      expressing three costimulatory molecules, B7.1, ICAM-1, and LFA-3 (rV-TRICOM), in
      patients with metastatic melanoma. A standard dose escalation phase I clinical
      trial was performed. Thirteen patients were enrolled and 12 were available for
      follow-up. Local vaccination was feasible, with only low-grade injection site
      reactions associated with mild fatigue and myalgia reported. There was one
      occurrence of grade 1 vitiligo. Overall there was a 30.7% objective clinical
      response, with one patient achieving a complete response for more than 22 months.
      An inverse association was detected between anti-vaccinia antibody and anti
      vaccinia T cell responses. Patients who failed to respond to vaccination but
      received high-dose interleukin-2 had a trend toward improved survival.
      Collectively, these results confirm the safety profile and feasibility of direct
      injection of vaccinia virus expressing multiple costimulatory molecules in
      patients with established tumors. Further clinical investigation is needed to
      better define the role of antigen, adjuvant cytokines, costimulation, and cross
      presentation in the host immune response to local vaccination with vaccinia
      viruses expressing immunomodulatory molecules.

PMID- 16454662
TI  - Membrane lipid composition and the interaction of pardaxin: the role of
      cholesterol.
AB  - Modulation by pardaxin of the phase transitions of dimyristoyl
      phosphatidylcholine, 1-stearoyl-2-oleoyl phosphatidylcholine or 1-stearoyl-2
      oleoyl phosphatidylglycerol in the presence or absence of cholesterol was studied
      by differential scanning calorimetry. The transition enthalpy of each of the
      phospholipids was lowered by pardaxin and there was a small decrease in the
      transition temperature. Addition of cholesterol and pardaxin to dimyristoyl
      phosphatidylcholine resulted in a very marked lowering of the transition
      temperature. Although the peptide broadens the transition of the pure
      phospholipids, it sharpens the transition of mixtures of the phospholipids with
      cholesterol. This and the observation that pardaxin also causes the formation of
      crystallites of anhydrous cholesterol, suggest that the peptide promotes
      redistribution of cholesterol in the membrane.

PMID- 16454658
TI  - A simplified approach to improve the efficiency and safety of ex vivo
      hematopoietic gene therapy in fanconi anemia patients.
AB  - Fanconi anemia (FA) is an inherited DNA repair disorder characterized by genetic
      instability of cells lacking a functional FA/BRCA pathway. Previous studies have
      shown that in vitro stimulation of bone marrow cells (BMCs) from FA mice promotes
      apoptosis, reduces the reconstitution ability of the stem cells, and induces
      myelodysplasia and myeloid leukemia upon reinfusion of the cells. This suggests
      the convenience of adapting standard protocols of gene therapy to FA. Here we
      show that the reserve of BM progenitors in FA patients is generally below 20% of
      normal values. Because this reduced reserve could activate the cycling of BM
      progenitors, we developed a simplified protocol to transduce BMCs from FA
      patients with gammaretroviral vectors. We demonstrate that a short in vitro
      manipulation (12-24 hr) of fresh mononuclear BMCs is sufficient to transduce 42%
      of hematopoietic progenitors from FA-A patients, in the absence of in vitro
      prestimulation. When FANCA-expressing vectors were used, this simple procedure
      reversed the phenotype of the BM progenitors from these patients. We propose that
      our approach will be more efficient and safer compared with standard gene therapy
      protocols for FA.

PMID- 16454663
TI  - A three-dimensional homology model of the O-acetylserine sulfhydrylase-B from
      Salmonella typhimurium.
AB  - O-acetylserine sulfhydrylase (OASS) catalyzes the last step in the cysteine
      biosynthetic pathway in enteric bacteria and plants. The overall pathway involves
      the substitution of the beta-acetoxy group of O-acetyl-L-serine with inorganic
      bisulfide. Two isozymes are present in S. typhimurium, the A- and B-isozymes,
      expressed under aerobic and anaerobic conditions, respectively. No crystal
      structure is presently available for the B-isozyme. Kinetic data indicate the
      catalytic mechanism of OASS-B is ping-pong, as found for the A-isozyme, but
      kinetic parameters and substrate specificity differ. In order to estimate whether
      structural differences may be responsible for the kinetic differences, a homology
      model was built using the structure of OASS-A as the template for the OASS-B
      model. The beta-subunit of tryptophan synthase and cystathionine beta-synthase
      were used for comparison. Differences between the OASS-A structure and the
      homology model for OASS-B are discussed.

PMID- 16454664
TI  - Novel plastocyanin containing phenylalanine-83 from the gymnosperm Ginkgo biloba.
AB  - Plastocyanin was purified from the gymnosperm Ginkgo biloba L., and its complete
      amino acid sequence was determined. The protein was shown to contain Phe-83
      instead of Tyr-83 conserved in other land plant plastocyanins. This is the first
      report of the characterization and complete amino acid sequence of a gymnosperm
      plastocyanin.

PMID- 16454665
TI  - The cardioprotective peptide, urocortin, activates cardiac KATP channels in adult
      rat.
AB  - Urocortin (UCN), an endogenous cardioprotective peptide, has been reported to
      activate several ion channels but its effects on the cardiac KATP channels are
      unknown. In this paper, we showed that adult rat cardiac myocytes had small KATP
      currents that could be increased 20-fold by pinacidil. UCN also concentration
      dependently activated the KATP current and this effect was influenced by ATP and
      PKA inhibitor peptide, Rp-cAMPS.

PMID- 16454666
TI  - Fragment library-based representation system for protein conformation.
AB  - The representation system for protein conformation has a crucial effect on the
      speed of various protein-related simulations, including ab initio protein
      structure prediction and protein-protein docking simulation. Usually, the finer a
      representation system, the longer is the computational time required to employ
      the representation system in simulations. On the other hand, very coarse lattice
      systems cannot be directly applied to the simulation problems with real proteins.
      We report a new, fragment library-based protein conformation representation
      system, prepared by clustering amino acid conformations from 154 proteins. This
      system was composed of 64 most representative fragments per each amino acid, and
      based on the unified residue approach in which two spheres per amino acid were
      used. It could represent the conformation of the 82 proteins in an independent
      test set with the mean and standard deviation RMSD of 1.01 and 0.09 A,
      respectively, based on the position of alpha carbons and the centers of mass of
      sidechains.

PMID- 16454667
TI  - Sequential events in ribonuclease A thermal unfolding characterized by two
      dimensional infrared correlation spectroscopy.
AB  - The conformational changes in the thermal denaturation of bovine pancreatic
      ribonuclease A was followed with infrared spectra and analyzed by second
      derivative and two-dimensional correlation techniques. By analyzing the
      sequential events in each transition stage, the results were consistent with a
      step-wise thermal denaturation mechanism in which the structural adjustment of
      the N-terminal and the opening of the central structure of the protein come
      before the main unfolding process. Non-native turns were found to form along with
      the unfolding of the native structures. The central region that is composed of
      some beta-sheet and alpha-helical structures was found to be the most stable part
      that might form the residual structure at high temperatures.

PMID- 16454669
TI  - Structure study of recombinant RGD-hirudin by vibrational and circular dichroism
      spectroscopy.
AB  - The secondary structure of a new type of recombinant RGD-hirudin, which has the
      activities of anti-thrombin and anti-platelet aggregation, has been studied by
      Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy and circular
      dichroism (CD) methods. The distribution of various secondary structure elements
      was determined using only a very small amount of sample protein. It was found
      that the recombinant RGD-hirudin contains about 26% extended chain, 21% beta-turn
      and 53% unordered structure, leaving no alpha-helix. The results showed that the
      regular secondary structure of recombinant RGD-hirudin is increased compared with
      wild-type hirudin. The RGD segment that is located at the end of a long arm of a
      beta-sheet is thought to play an important role in the additional function of
      anti-platelet aggregation. Throughout the experiments, FT-IR, Raman spectroscopy
      and CD generated mutually reinforcing results.

PMID- 16454668
TI  - Expression and purification of a putative tumor suppressor gene PP5715 in E. coli
      with growth inhibition of hepatocellular carcinoma cells.
AB  - PP5715 is a putative tumor suppressor gene that encodes a protein of 199 amino
      acids. Expression of PP5715 in E. coli was mainly as inclusion bodies. The
      recombinant protein was purified by a NTA-Ni2+ affinity column, refolded by
      dialysis, and shown to suppress growth of two human hepatocellular carcinoma cell
      lines using the MTT assay or the clonogenic assays. Computer analysis and fusion
      expression of PP5175 and GFP showed that PP5715 may be a secretory protein. It
      may bind to receptors on the membrane surface and thus induce regulation of cell
      growth. These preliminary results suggest that protein PP5715 may be a new tumor
      suppressor with growth inhibition effects on hepatocellular carcinoma cells.

PMID- 16454670
TI  - Antibiotic activity of antimicrobial peptide against Pseudomonads isolated from a
      patient with gallstones.
AB  - We investigated the in vitro antibiotic activity of the 19-amino acid
      antimicrobial peptide HP (2-20), derived from the N-terminus of Helicobacter
      pylori Ribosomal Protein L1 (RPL1), against antibiotic susceptible and resistant
      pathogens from a patient with gallstones. HP (2-20) was active against antibiotic
      susceptible and antibiotic-resistant clinical isolates of pathogens from a
      patient with gallstones, but this peptide showed no hemolytic activity against
      normal human erythrocytes. HP (2-20) acted synergistically with ciprofloxacin
      against pathogenic bacteria. Fluorescence activated flow cytometry revealed that
      the effect of HP (2-20) was dependent on energy and salt concentration. In
      addition, scanning electron microscopy showed that HP (2-20) caused significant
      morphological alterations to the cell surface of pathogens. Using 16S rDNA
      sequences, we found that isolates from bile were 100% homologous to Pseudomonas
      aeruginosa. These findings suggest that HP (2-20) may be useful clinically as an
      antibiotic against acquired pathogens from patients with gallstones and against
      pathogens resistant to other antibiotics.

PMID- 16454671
TI  - Predominant expression of rTERTb, an inactive TERT variant, in the adult rat
      brain.
AB  - The full-length and four alternatively spliced variant mRNA transcripts of rat
      TERT were identified. One of the variant, rTERTb, was predominantly expressed
      during brain development in accordance with the decrease in telomerase activity.
      The rTERTb mRNA encoded an inactive truncated protein. Alternative splicing of
      TERT may be important during brain development.

PMID- 16454672
TI  - Oxidative folding of conotoxins in immobilized systems.
AB  - We tested two alternative oxidation strategies to produce conotoxins alpha-GI and
      micro-PIIIA. The peptides were either reversibly immobilized on a solid support
      and then oxidized, or the immobilized disulfide reagent (CLEAR-OX(trade mark))
      was used to oxidize the peptides. Both strategies appeared more efficient at
      higher peptide concentrations, consistent with pseudo-dilution effects.

PMID- 16454673
TI  - Biophysical characterization of the non-fusogenic interaction between liposomes
      and the shrimp bifunctional lipoprotein-beta-glucan binding protein HDL/BGBP.
AB  - Shrimp High Density Lipoprotein-beta-Glucan Binding Protein (HDL/BGBP) has been
      studied by its role in nutrition and innate defense. Although the mechanisms of
      lipid loading are still unknown, HDL-BGBP binds and aggregates phospholipids
      vesicles in vitro. To gain insights into the HDL-BGBP mechanism of interaction
      with membranes, we have used fluorescence spectroscopy and electron microscopy.
      Data show that HDL-BGBP does not induce membrane fusion, leakage nor lipid
      exchange, although microstructural changes are clearly observed. This work
      supports a model where protein aggregation leads to liposome clustering. Such
      interaction may be a critical factor for the activation of the shrimp blood cell
      in vivo.

PMID- 16454674
TI  - The monomers of the P2X1 receptor model and KcsA protein share a similar
      structural fold.
AB  - There is evidence that the P2X1 receptor subunit is involved in apoptosis,
      platelet aggregation, and smooth muscle contraction. The conformation of the
      membrane-embedded, ligand-gated mouse P2X1 glycoprotein, a monovalent-bivalent
      cation channel-forming receptor, is predicted. The first step is based on
      secondary structure prediction. The secondary structure is converted into a three
      dimensional geometry. Then, the secondary and tertiary structures are optimized
      by using the quantum chemistry RHF/3-21G minimal basic set and the all-atom
      molecular mechanics AMBER96 force field. The fold of the membrane-embedded
      protein is simulated by a suitable dielectric. The structure is refined using a
      conjugate gradient minimizer (Fletcher-Reeves modification of the Polak-Ribiere
      method). Although the mouse P2X1 receptor subunit is more complex (388 amino
      acids) than the KcsA protein (160 amino acids), the overall folds are similar.
      The geometry optimized P2X1 receptor subunit is freely available for academic
      researchers on e-mail request (PDB format).

PMID- 16454675
TI  - Preliminary functional characterization, cloning and primary sequence of
      Fastuosain, a cysteine peptidase isolated from fruits of Bromelia fastuosa.
AB  - The present work reports the characterization of Fastuosain, a novel cysteine
      protease of 25kDa, purified from the unripe fruits of Bromelia fastuosa, a wild
      South American Bromeliaceae. Proteolytic activity, measured using casein and
      synthetic substrates, was dependent on the presence of thiol reagents, having
      maximum activity at pH 7.0. The present work reports cDNA cloning of Fastuosain;
      cDNA was amplified by PCR using specific primers. The product was 1096pb long.
      Mature fastuosain has 217 residues, and with the proregion has a total length of
      324 residues. Its primary sequence showed high homology with ananain(74%), stem
      bromelain (66%) and papain (44%).

PMID- 16454676
TI  - Ca2+ binding effects on the C2 domain conformation of human cytosolic
      phospholipase A2.
AB  - It has been reported that the cooperative binding of calcium ions indicated a
      local conformational change of the human cytosolic phospholipase A2 (cPLA2) C2
      domain (Nalefski et al., (1997) Biochemistry 36, 12011-12018). However its
      structural evidence is less known (Malmberg et al., (2003) Biochemistry 42, 13227
      13240). In this letter, life-time decay and fluorescence quenching techniques
      were employed to compare the calcium-induced conformational changes. The life
      time decay parameters and fluorescence quenching constant changes were small
      between the apo- and holo-C2 domains when tryptophan residue was excited at 295
      nm. In contrast, the quenching constant change was large, from 0.52 M(-1) for the
      apo-C2 to 8.8 M(-1) for the holo-C2 domain, when tyrosine residues were excited
      at 284 nm. Our results provide new information on amino acid side chain
      orientation change at calcium binding loop 3, which is necessary for Ca2+ binding
      regulated membrane targeting of human cytosolic phospholipase A2.

PMID- 16454677
TI  - Potential for ultrafast protein separations with capillary-channeled polymer (C
      CP) fiber columns.
AB  - Capillary-channeled polymer (C-CP) fibers are demonstrated as a potential
      stationary phase for liquid chromatography separation of protein mixtures.
      Separation of a synthetic mixture of four proteins is accomplished within a 45
      second window using a conventional revered-phase (RP) gradient, at a mobile phase
      flow rate of 7 mL/min (10,200 mm/min).

PMID- 16454678
TI  - Pattern of positions sensitive to mutations in human haemoglobin alpha-chain.
AB  - In this study, we used the distribution rank, which has been developed by us over
      the past several years, to quantify 134 mutations in the human hemoglobin alpha
      chain in order to gain an insight into the general pattern in mutations. The
      results suggest that the pattern presented by distribution rank can approximately
      estimate the positions that are sensitive to mutations in human hemoglobin alpha
      chain.

PMID- 16454680
TI  - Fast mass spectrometry-based methodologies for pharmaceutical analyses.
AB  - Historically, most bioanalytical methods for drug analysis in pharmaceutical
      industry were developed using HPLC coupled with UV or fluorescence detection.
      However, there is a trend toward interfacing separation technologies with more
      sensitive tandem mass spectrometry (MS/MS)-based systems. MS/MS detection offers
      complete resolution of the parent compounds from their first pass metabolites to
      avoid extra efforts for separation and sample clean-up procedures resulting in
      shorter run times. With the increasing demand for ever faster screening, there is
      a continuing demand for bioanalytical methods possessing higher sample throughput
      for both in vitro and in vivo drug metabolism and pharmacokinetic evaluations to
      accelerate the discovery process. This review focuses on the current approaches
      for fast MS-based assays (cycle-time less than 5 min) of pharmaceuticals and
      their metabolites that have been reported in the peer-reviewed publications.

PMID- 16454682
TI  - Straightforward three-component palladium-catalysed synthesis of pyridazin-3(2H)
      one libraries.
AB  - A simple and straightforward three-component methodology for the solution phase
      high-throughput synthesis of 2,5-disubstituted pyridazin-3(2H)-one libraries has
      been developed. The diversity at position 5 of the heterocycle is determined by
      the use of Suzuki, Sonogashira, Heck or Stille coupling.

PMID- 16454681
TI  - Development of a novel high-throughput assay for the investigation of GlyT-1b
      neurotransmitter transporter function.
AB  - The glycine transporter (GlyT-1b) is a Na(+)/Cl(-)-dependent electrogenic
      transporter which mediates the rapid re-uptake of glycine from the synaptic
      cleft. Based on its tissue distribution, GlyT-1 has been suggested to co-localise
      with the NMDA receptor where it may modulate the concentration of glycine at its
      co-agonist binding site. This data has led to GlyT-1 inhibitors being proposed as
      targets for disorders such as schizophrenia and cognitive dysfunction.
      Radiolabelled uptake assays (e.g. [(3)H]glycine) have been traditionally used in
      compound screening to identify glycine transporter inhibitors. While such an
      assay format is useful for testing limited numbers of compounds, the
      identification of novel glycine uptake inhibitors requires a functional assay
      compatible with high-throughput screening (HTS) of large compound libraries.
      Here, the authors present the development of a novel homogenous cell-based assay
      using the FLIPR membrane potential blue dye (Molecular Devices) and FLEXstation.
      Pharmacological data for the GlyT-1 inhibitors Org 24598 and ALX 5407 obtained
      using this novel electrogenic assay correlated well with the conventional [(3)H]
      glycine uptake assay format. Furthermore, the assay has been successfully
      miniaturised using FLIPR(3) and therefore has the potential to be used for high
      throughput screening.

PMID- 16454683
TI  - Development of a fluorescence peptide chip for the detection of caspase activity.
AB  - Proteases play a key role in cell functions, and it is very important to monitor
      their activities for drug screening and diagnosis of diseases. In the present
      study, a new class of fluorescence probe, into which a fluorophore and a quencher
      have been introduced, was developed and applied to the on-chip detection of
      caspase-3 activity. This probe is non fluorescent in the absence of caspase-3.
      However, when it is treated with active caspase-3, the fluorescence intensity
      increases dependent on the caspase-3 activity due to the cleavage of the quencher
      containing moiety on a glass slide. This caspase-dependent increase in the
      fluorescence intensity was also detected when the glass slide immobilizing the
      probe peptide was treated with cell lysate stimulated by staurosporine (STP),
      which is an apoptosis-inducing agent. On the other hand, such an increase was not
      detected in the case of control cell lysate without STP-stimulation. The
      developed system is a rapid and sensitive method and is useful for the direct
      measurement of protease activity on a glass array.

PMID- 16454684
TI  - Anti-endotoxin agents. 3. Rapid identification of high-affinity
      lipopolysaccharide-binding compounds in a substituted polyamine library.
AB  - Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are an integral part of
      the outer leaflet of the outer-membrane of Gram-negative bacteria.
      Lipopolysaccharides play a pivotal role in the pathogenesis of 'Septic Shock', a
      major cause of mortality in the critically ill patient, worldwide. The
      sequestration of circulatory endotoxin may be a viable therapeutic strategy for
      the prophylaxis and treatment of Gram-negative sepsis. We have earlier shown that
      the pharmacophore necessary for small molecules to bind LPS involves two
      protonatable cationic functions separated by about 15 A, permitting the
      simultaneous interaction with the negatively charged phosphates on lipid A, the
      toxically active center of endotoxin. In this report, screening of a multi
      thousand membered polyamine library through the combined use of computational and
      bioassay-guided screens resulted in the discovery of two novel classes of LPS
      binding agents. These are represented by the 1) spermine sulfonamides and 2) C
      aryl-substituted spermine analogs. We present the selection approach, screening
      results, computational multivariate analyses and initial structure-activity
      relationship evaluation herein.

PMID- 16454686
TI  - Recognition of protein coding genes in the yeast genome based on the relative
      entropy of DNA.
AB  - In this paper, a new protein coding gene-finding algorithm specific for the yeast
      genome at 96% accuracy is proposed. Five-fold cross-validation tests are
      performed to confirm the above accuracy. By the new algorithm, the number of
      protein coding genes in the yeast genome is re-estimated. The estimate is based
      on the assumption that the unknown genes have similar statistical properties to
      the known genes. It is found that the number of protein coding genes in the 16
      yeast chromosomes is less than or equal to 5,873, significantly coincident with
      the widely accepted range 5,800-6,000.

PMID- 16454685
TI  - Comparison of G-protein coupled receptor desensitization-related beta-arrestin
      redistribution using confocal and non-confocal imaging.
AB  - High Content Screening (HCS), a combination of fluorescence microscopic imaging
      and automated image analysis, has become a frequently applied tool to study test
      compound effects in cellular disease-modelling systems. In this work, we compared
      a confocal and a non-confocal cellular HCS system, the IN Cell Analyzers(1) 3,000
      and 1,000, respectively. As a cellular model system we used the Transfluor
      technology in the 384-well microtiter plate (MTP) format. The Transfluor HCS
      assay for G-protein coupled receptor (GPCR) activation is based on the
      recruitment of a green fluorescent protein-labelled arrestin (ArrGFP) from the
      cytosol to the plasma membrane. We investigated two GPCRs, the wild-type (wt)
      beta2 adrenergic receptor (beta2AR) and the beta2AR-enhanced (E), a C-terminally
      mutated receptor with a higher affinity to arrestin. Upon agonist stimulation,
      the beta2AR-wt induced the redistribution of ArrGFP to coated pits, the beta2AR-E
      maintained the interaction with ArrGFP down to the formation of endocytic
      vesicles. Our findings reveal that the assay is feasible on both instruments,
      with sufficiently robust Z' statistics. Improved Z' statistics, though, are
      achieved with the confocal system, particularly in case of weak signals.
      Moreover, throughput is dramatically higher for the IN Cell Analyzer 3,000. We
      conclude that, depending on the needs for throughput and assay biology, either
      instrument may fulfil a successful role in the drug discovery process. Confocal
      optics, however, provide a better basis for the detection of smaller subcellular
      structures with lower fluorescence intensity.

PMID- 16454687
TI  - A high-throughput phage display screening method using a combination of real-time
      PCR and affinity chromatography.
AB  - Phage display is one of the best methods to identify drug targets, although
      technical problems including imprecision in quantifying phage and false-positive
      results are common. To address these difficulties, we propose two methods to more
      rapidly identify drug-binding phage particles. First, quantification of phage
      using SYBR Green Real-time PCR significantly improved accuracy and
      reproducibility. Second, affinity-column chromatography for selection of drug
      binding phage particles concentrated particles more than a 96-well plate, making
      a phage amplification step, which can bias phage distribution, unnecessary. The
      methods proposed here should be suitable for high-throughput phage-display
      screenings and ultimately lead to more rapid identification of drug targets.

PMID- 16454688
TI  - Oligosaccharide synthesis and library assembly by one-pot sequential
      glycosylation strategy.
AB  - The oligosaccharide residue in glycoconjugates located in cell membranes is
      responsible for intercellular recognition and interaction: it acts as a receptor
      for proteins, hormones, and microorganisms and governs immune reactions. These
      significant activities have stimulated great interest in the field of
      oligosaccharides and glycoconjugates. Although many advances have been made in
      the synthesis of oligosaccharides, more convenient and efficient methods are
      still needed. This review describes one of these new methods-the one-pot
      sequential glycosylation approach as a potent tool for oligosaccharide assembly.
      The oligosaccharide library construction in a one-pot fashion is also summarized.

PMID- 16454689
TI  - Inhibition constants, inhibitor concentrations and the prediction of inhibitory
      drug drug interactions: pitfalls, progress and promise.
AB  - Strategies and standards for predicting the likelihood of pharmacokinetically
      significant inhibitory drug-drug interactions for drug development purposes which
      rely primarily on projected in vivo concentrations of cytochrome P450 (CYP) or
      transporter inhibitors, [I], and in vitro estimates of their inhibitory
      constants, K(i), were specified in several commentaries based upon a conference
      held by the European Federation of Pharmaceutical Sciences (EUFEPS) several years
      ago. Since then the application of those strategies and standards has met with
      varying degrees of success. Many of the vexing issues that were identified in the
      EUFEPS Conference Report remain, while other issues are systematically being
      resolved. This article briefly reviews the underlying strategy in the prediction
      of the significance of inhibitory DDIs using [I]/K(i) ratios; some of the
      difficulties or pitfalls associated with the predictive application of [I]/K(i)
      ratios; and some of the recent refinements of the general strategy.

PMID- 16454690
TI  - Early development of therapeutic biologics--pharmacokinetics.
AB  - Modern biologics are biotechnology-derived pharmaceuticals. They are mostly used
      for diagnosis, prevention and treatment of serious and chronic diseases. Today,
      therapeutic biologics range from traditional biologics like blood and blood
      components, fractionated blood products, and antitoxins to modern biologics such
      as monoclonal antibodies, cytokines (e.g. interferon, interleukine), tissue
      growth factors, vaccines directed against non-infectious disease targets, and
      gene transfer products. Chemical as well as pre-clinical development are major
      challenges for biologics due to their different physicochemical properties
      (mostly protein structure) compared to small molecules. They demonstrate much
      more complex pharmacokinetic behaviour, which strongly influences their pre
      clinical testing strategy. Biologics are often highly species-specific in action
      and immunogenic in test animal species and humans. Immunogenicity of therapeutic
      biologics may influence their pharmacokinetic behaviour as well as
      pharmacodynamics and toxicity. Biologics are frequently regulated by different
      procedures compared to small molecules. New guidances are evolving which reflect
      the rapid development of new technologies in this field. Bioanalytical method
      development and validation is a prerequisite not exclusively for pharmacokinetic
      studies but for the whole pre-clinical and clinical development. Due to their
      unique properties, different kinds of bioanalytical assays (mass assays, activity
      assays, immunogenicity assays) are necessary in early development of biologics.

PMID- 16454691
TI  - Cytochrome P450 and anticancer drugs.
AB  - Cytochrome P450 (CYP) is involved in the metabolism of a variety of anticancer
      drugs. CYP activities are known to be modified by several factors including
      genetic polymorphisms, changes in physiological conditions such as age, disease
      status or intake of certain drugs or foods or environmental factors such as
      smoking. These factors may cause interindividual differences in the
      pharmacokinetic profiles of anticancer drugs, leading to the variations of
      efficacy or toxicity of the drugs. Genetic polymorphisms present in CYPs
      sometimes result in the reduced activity of the enzymes causing low metabolic
      clearance of drugs or low production of active metabolites. For example, the
      formation of endoxifen, which is an active metabolite of tamoxifen, was less in
      patients with inactive polymorphic CYP2D6 than those with the wild type enzyme.
      CYP3A is the most abundant CYP expressed in the human liver and the small
      intestine that is involved in the metabolism of various anticancer drugs. The
      catalytic activity of CYP3A shows a large interindividual variability giving rise
      to large interindividual differences in the pharmacokinetic profiles of some
      anticancer drugs. So far, many attempts have been made to monitor the phenotypic
      activity of CYP3A in order to reduce the pharmacokinetic variations of anticancer
      drugs. Erythromycin, midazolam and cortisol are commonly used to monitor in vivo
      hepatic CYP3A activity. These methods have been applied to reduce the
      pharmacokinetic variations of docetaxel. Drug-drug interactions related to CYPs
      also modulate the pharmacokinetic profiles of anticancer drugs. These factors
      should be considered when trying to optimize and individualize chemotherapy.

PMID- 16454692
TI  - Tissue distribution and pharmacodynamics: a complicated relationship.
AB  - With few exceptions, drugs exert their effects not within the plasma compartment,
      but in the defined target tissues. The process of drug distribution to the active
      site constitutes the "link-bridge" of the pharmacokinetic/pharmacodynamic (PK/PD)
      relationship. In spite of the importance of drug distribution as a key factor in
      determining pharmacologic response, research on drug distribution has
      historically received much less attention than that of absorption, metabolism,
      and excretion. The negligence of research on drug distribution is due mainly to
      the inaccessibility of the target tissues for obvious ethical reasons. In
      addition, lack of reliable experimental tools to assess the distribution process
      is also a major contributing factor. Because of this negligence, drug
      distribution has been referred to as "the forgotten relative in clinical
      pharmacokinetics." Although recent advances in molecular biology have led to the
      identification of many drug transporters, many of the processes of drug
      distribution are still not fully understood. The primary aim of this article is
      to provide new insight into the mechanisms of drug distribution, with an attempt
      to describe the relationship between the drug distribution and pharmacologic
      response. In addition, the factors that affect the processes of drug distribution
      will also be reviewed. Also, validity of some key assumptions that are used to
      relate the processes of tissue distribution with pharmacologic activity will be
      discussed.

PMID- 16454693
TI  - Altered CYP expression and function in response to dietary factors: potential
      roles in disease pathogenesis.
AB  - Increasing evidence implicates dietary factors in the progression of diseases,
      including certain cancers, diabetes and obesity. Diet also regulates the
      expression and function of CYP genes, which impacts on drug elimination and may
      also significantly affect disease pathogenesis. Upregulation of CYPs 2E1 and 4A
      occurs after feeding of experimental diets that are high in fats or
      carbohydrates; these diets also promote hepatic lipid infiltration, which is a
      component of the metabolic syndrome that characterises obesity. Increased
      availability of lipid substrates for CYPs can enhance free radical production and
      exacerbate tissue injury. Similar processes may also occur in other models of
      experimental disease states that exhibit a component of altered nutrient
      utilization. Food-derived chemicals, including constituents of cruciferous
      vegetables and fruits, modulate CYP expression and the expression of genes that
      encode cytoprotective phase II enzymes. Certain dietary indoles and flavonoids
      activate CYP1A expression either by direct ligand interaction with the aryl
      hydrocarbon receptor (AhR) or by augmenting the interaction of the AhR with
      xenobiotic response elements in CYP1A1 and other target genes. Other dietary
      chemicals, including methylenedioxyphenyl (MDP) compounds and isothiocyanates
      also modulate CYP gene expression. Apart from altered CYP regulation, a number of
      dietary agents also inhibit CYP enzyme activity, leading to pharmacokinetic
      interactions with coadministered drugs. A well described example is that of
      grapefruit juice, which contains psoralens and possibly other chemicals, that
      inactivate intestinal CYP3A4. Decreased presystemic oxidation by this CYP
      increases the systemic bioavailability of drug substrates and the likelihood of
      drug toxicity. Dietary interactions may complicate drug therapy but inhibition of
      certain CYP reactions may also protect the individual against toxic metabolites
      and free radicals generated by CYPs. Chemicals in teas and cruciferous vegetables
      may also inhibit human CYP enzymes that have been implicated in the bioactivation
      of chemical carcinogens. Thus, food constituents modulate CYP expression and
      function by a range of mechanisms, with the potential for both deleterious and
      beneficial outcomes.

PMID- 16454694
TI  - Inhibition of sulfotransferases by xenobiotics.
AB  - The sulfotransferase (SULT) family comprises important phase II conjugation
      enzymes for the detoxification of xenobiotics and modulation of the activity of
      physiologically important endobiotics such as thyroid hormones, steroids, and
      neurotransmitters. SULT enzymes catalyze the transfer of a sulfuryl group,
      donated by 3'-phosphoadenosine-5'-phosphosulfate (PAPS), to an acceptor substrate
      that may be a hydroxy group or an amine group in a process originally called
      sulfation, but more correctly referred to as sulfonation or sulfurylation. SULT
      activity may be inhibited when humans are exposed to certain xenobiotics
      including drugs (mefenamic acid, salicylic acid, clomiphene, danazol etc.),
      dietary chemicals (catechins, food colorants, flavonoids and phytoestrogens
      etc.), and environmental chemicals (hydroxylated polychlorinated biphenyls,
      hydroxylated polyhalogenated aromatic hydrocarbons, pentachlorophenol, triclosan
      and bisphenol A, etc.). Inhibition of individual SULT isoforms may cause adverse
      effects on human health. For example, hydroxylated polychlorinated biphenyls have
      been shown to interfere with the transport of thyroid hormones, inhibit estradiol
      sulfonation, and inhibit thyroid hormone sulfonation, thereby potentially
      disrupting the thyroid hormone system. Formation of sulfate conjugates of toxic
      xenobiotics usually decreases their toxicity, so inhibition of this pathway may
      lead to prolonged exposure to the compounds. Conversely, some sulfate conjugates
      are chemically reactive, inhibition of their formation may protect from toxicity.
      This manuscript will review the literature concerning the inhibition of SULTs by
      xenobiotics including isoform-selective effects, inhibition kinetics and health
      effects resulting from the inhibition.

PMID- 16454695
TI  - Topotecan is a substrate for multidrug resistance associated protein 4.
AB  - Topotecan (TPT) is a semisynthetic water-soluble derivative of camptothecin (CPT)
      used as second-line therapy in patients with metastatic ovarian carcinoma, small
      cell lung cancer, and other malignancies. However, both dose-limiting toxicity
      and tumor resistance hinder the clinical use of TPT. The mechanisms for
      resistance to TPT are not fully defined, but increased efflux of the drug by
      multiple drug transporters including P-glycoprotein (PgP), multidrug resistance
      associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) from
      tumor cells has been highly implicated. This study aimed to investigate whether
      overexpression of human MRP4 rendered resistance to TPT by examining the
      cytotoxicity profiles using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazonium bromide (MTT) assay and cellular accumulation of TPT in HepG2
      cells stably overexpressing MRP4. Two kinds of cell lines, HepG2 with insertion
      of an empty vector plasmid (V/HepG2), HepG2 cells stably expressing MRP4
      (MRP4/HepG2), were exposed to TPT for 4 or 48 hr in the absence or presence of
      various MRP4 inhibitors including DL-buthionine-(S,R)-sulphoximine (BSO),
      diclofenac, celecoxib, or MK-571. The intracellular accumulation of TPT and
      paclitaxel (a PgP substrate) by V/HepG2 and MRP4/HepG2 cells was determined by
      incubation of TPT with the cells and the amounts of the drug in cells were
      determined by validated HPLC methods. The study demonstrated that MRP4 conferred
      a 12.03- and 6.86-fold resistance to TPT in the 4- and 48-hr drug-exposure MTT
      assay, respectively. BSO, MK-571, celecoxib, or diclofenac sensitised MRP4/HepG2
      cells to TPT cytotoxicity and partially reversed MRP4-mediated resistance to TPT.
      In addition, the accumulation of TPT was significantly reduced in MRP4/HepG2
      cells compared to V/HepG2 cells, and one-binding site model was found the best
      fit for the MRP4-mediated efflux of TPT, with an estimated K(m) of 1.66 microM
      and V(max) of 0.341 ng/min/106 cells. Preincubation of MRP4/HepG2 cells with BSO
      (200 microM) for 24 hr, celecoxib (50 microM), or MK-571 (100 microM) for 2 hr
      significantly increased the accumulation of TPT over 10 min in MRP4/HepG2 cells
      by 28.0%, 37.3% and 32.5% (P < 0.05), respectively. By contrast, there was no
      significant difference in intracellular accumulation of paclitaxel in V/HepG2 and
      MRP4/HepG2 cells over 120 min. MRP4 also rendered resistance to adefovir
      dipivoxil (bis-POM-PMEA) and methotrexate, two reported MRP4 substrates. MRP4 did
      not exhibit any significant resistance to other model drugs including
      vinblastine, vincristine, etoposide, carboplatin, cyclosporine and paclitaxel in
      both long (48 hr) and short (4 hr) drug-exposure MTT assays. These findings
      indicate that MRP4 confers resistance to TPT and TPT is the substrate for MRP4.
      Further studies are needed to explore the role of MRP4 in resistance to, toxicity
      and pharmacokinetics of TPT in cancer patients.

PMID- 16454696
TI  - Asthma, allergy and chemokines.
AB  - In the human, chemokines represent a structurally related family of more than
      forty cytokines which act on distinct subsets of leukocytes via specific G
      protein-coupled receptors expressed on the cell surface. The induction of select
      repertoires of chemokines following exposure to allergen provides a biological
      basis for the selective leukocyte recruitment, observed both clinically and
      experimentally. The chemokine receptor CCR3 is expressed on the cell surface of
      eosinophils, Th2 lymphocytes, basophils and mast cells and binds the Eotaxin
      family of chemokines (CCL11, CCL24 and CCL26), whose production is upregulated
      following allergen challenge. Once recruited, eosinophils are a source of growth
      factors associated with tissue repair and remodelling and also have the ability
      to induce tissue damage, a capacity that extends from their traditional role in
      protecting the host against parasitic worms. Thus, impairment of their
      recruitment by selective blockade of the CCR3:eotaxin axis represents an
      attractive target for the therapeutic treatment of asthma. In this review, we
      will examine recent developments in the field and highlight the roles of other
      chemokine:chemokine receptor axes implicated in leukocyte recruitment during
      allergic inflammation.

PMID- 16454697
TI  - Chemokines as potential therapeutic targets in atherosclerosis.
AB  - Atherosclerosis is a chronic disease with high morbidity and mortality around the
      globe. It is characterized by chronic inflammation of the vessel wall, which is
      perpetuated by the continuous migration of cells to and within the
      atherosclerotic lesion. Chemokines (CK) and chemokine receptors (CKR) together
      with other chemoattractants and adhesion molecules are major mediators
      facilitating this process. Many CK/CKR (CC, CX3C and CXC) and other
      chemoattractants (e.g. leukotrienes) have been implicated in atherogenesis, but
      only a few have been validated as pathogenic by in vitro assays, in vivo
      experiments using gene-targeted animal models and genetic studies. Promising
      attempts are currently made to inhibit CK-dependent cell recruitment to lesion by
      using neutralizing antibodies, mutant proteins, viral and synthetic inhibitors or
      receptor antagonists. Some of the therapeutics have already entered clinical
      trials for other conditions and are about to be tested in human atherosclerosis.
      However, our limited understanding of the complex CK system and the functional
      specialization of individual CK/CKR, translatability of animal research into
      human population, limitations of current imaging techniques and surrogate markers
      for evaluation of the benefits of potential anti-CK compounds are still hampering
      therapeutic exploitation of the CK system in atherosclerosis. Hopefully we will
      be able to solve many of these issues in the near future and use this approach to
      control atherosclerotic disease in man.

PMID- 16454698
TI  - Chemokines and their receptors in central nervous system disease.
AB  - Almost a decade ago, it was discovered that the human deficiency virus (HIV)
      makes use of chemokine receptors to infect blood cells. This appreciation of the
      clinical relevance of specific chemokine receptors has initiated a considerable
      boost in the field of chemokine research. It is clear today that chemokine
      signaling orchestrates the immune system and is widely involved in both
      physiological and pathophysiological processes. Since the chemokine system offers
      various targets through which pathology could be influenced, most pharmaceutical
      companies have chosen this system as a therapeutic target for a variety of
      diseases. Here recent developments concerning the role of chemokines in diseases
      of the central nervous system (CNS) as well as their possible therapeutic
      relevance are discussed.

PMID- 16454699
TI  - Chemokines in gastrointestinal disorders.
AB  - The intestine is constantly challenged by food antigens and pathogens and is
      therefore in need of a good working innate and adaptive immune response.
      Chemokines are important modulators as they assure the directed movement of
      immune cells within the body. In addition, chemokines play an important role in
      hematopoiesis, angiogenesis and tumor metastasis. This review focuses on
      chemokines and gastrointestinal disorders, more particularly on inflammatory
      bowel diseases and gastrointestinal tumors. In a first part, the current
      knowledge on chemokine expression in inflammatory bowel diseases is summarized.
      Idiopathic inflammatory bowel diseases are characterized by an uncontrolled
      immune response. The resulting chronic inflammation of the intestine involves
      massive infiltration of immune cells, causing intestinal damage by the release of
      cytokines and proteolytic enzymes. Chemokines are believed to be key mediators in
      this process of aberrant leukocyte recruitment. Chemokine expression in
      inflammatory bowel disease strongly correlates with the grade of disease
      activity. The potential therapeutic use of chemokines in gastrointestinal tumors
      by the use of gene therapy is also reviewed. Chemokines have therapeutic
      potential in anti-tumor therapy by their angiostatic effect. On the other hand,
      chemokines can augment the cell-mediated adaptive immune response and thereby
      exert anti-tumor activity. However, chemokines can passively favor escape of
      tumor cells by stimulating the release of tissue degrading matrix
      metalloproteinases and can actively promote metastasis of chemokine receptor
      expressing tumor cells.

PMID- 16454700
TI  - Kidney diseases and chemokines.
AB  - Infiltrating inflammatory cells into the kidney mediate the initiation and
      progression of damage by direct cytotoxicity, the secretion of soluble factors
      such as cytokines and proteases, or by the subsequent induction of further immune
      response. Before leukocytes can exert their effects on renal damage or repair,
      they have to reach the site of injury. It has become clear in recent years that a
      group of small proteins called chemokines are the chemotactic cytokines
      considered to be the main regulators of directional leukocyte trafficking under
      homeostatic and inflammatory conditions. In this review, we summarize available
      in vivo studies on the neutralization of chemokines and chemokine receptors in
      renal inflammatory disease, and especially focus on the potential therapeutic
      effects of chemokine blockade in glomerulonephritis and renal transplantation.
      Although interference with chemokine expression holds great promises for the
      treatment of inflammatory renal diseases, it has been shown that such an approach
      may actually worsen in diseases under certain circumstances. This suggests that
      inhibition of chemokine expression and action must be time and compartment
      specific to provide therapeutic benefit for renal structure and function.

PMID- 16454701
TI  - Lymphoproliferative disorders and chemokines.
AB  - Chemokines are low molecular weight cytokines specialized in leukocyte
      recruitment. Recent studies have shown that tumor cells of hematopoietic and non
      hematopoietic origin express different chemokine receptors that may be involved
      in neoplastic cell growth, metastasis and angiogenesis. Human lymphoproliferative
      disorders arise from the malignant transformation of normal lymphoid cells frozen
      at discrete maturational stages. Studies performed with acute or chronic
      lymphoproliferative disorders have shown that CXCR4, the unique receptor for
      CXCL12, is up-regulated in many B and T cells malignancies and may be involved in
      metastatic localization of the neoplastic elements. Additional chemokine
      receptors are expressed in the individual lymphoproliferative disorders, but some
      of these are often non functional. Here we shall review the state of the art on
      chemokine receptor expression and function in human lymphoproliferative
      disorders, stressing the potential value of chemokines receptors as novel
      therapeutic targets. In this respect, small antagonistic peptides are being
      produced by pharmaceutical companies and hold great promise for clinical
      application.

PMID- 16454702
TI  - Chemokines in rheumatic diseases.
AB  - Chemotactic cytokines, termed chemokines, mediate the ingress of leukocytes into
      the inflamed synovium. In this review, authors discuss the role of the most
      relevant chemokines and chemokine receptors involved in chronic inflammatory
      rheumatic diseases. Rheumatoid arthritis was chosen as a prototype to discuss
      these issues, as the majority of studies on the role of chemokines in
      inflammatory diseases were carried out in arthritis. However, other rheumatic
      diseases including systemic lupus erythematosus, systemic sclerosis, Sjogren's
      syndrome, mixed connective tissue disease, polymyositis/dermatomyositis,
      antiphospholipid syndrome and systemic vasculitides are also discussed in this
      context. Apart from discussing the pathogenic role of chemokines and their
      receptors, authors also review the regulation of chemokine production by other
      inflammatory mediators, as well as the important relevance of chemokines for
      antirheumatic therapies.

PMID- 16454703
TI  - Targeting herpesvirus reliance of the chemokine system.
AB  - Viral infections depend on an intimate relationship between the infectious agent
      and the host cells. Viruses need the host cells for replication, while the innate
      and adaptive- immunesystem of the host is fighting to kill the infected cell in
      order to clear out the pathogen and survive the infection. However, since both
      virus and host exist, the organisms struggle must reach an ecological
      equilibrium. Among the best-studied interactions between viruses and the host
      immune system are those between herpesviruses and their hosts. Herpesviruses are
      known to devote a significant part of their large genomes on immuno-modulatory
      genes, some encoding chemokines or chemokine receptors. These genes, which may be
      dispensable for viral replication in vitro, are highly important for viral growth
      in vivo, for viral dissemination and disease progression. Indeed, all beta and
      gamma-herpesviruses have acquired homologs of both chemokines and chemokine
      receptors belonging to the 7 transmembrane (7TM) spanning, G protein-coupled
      receptor family. 7TM receptors are very efficient drug targets and are currently
      the most popular class of investigational drug targets. A notable trait for the
      virus encoded chemokine receptors seems to be their constitutive activity. The
      biological function of the constitutive activity is still unclear, but it has
      become clear that the receptors are involved in important parts of the viral
      lifecycle in vivo, and that the receptor signaling is involved in gamma
      herpesvirus mediated cell transformation. Therefore, blocking the signaling of
      these receptors will provide an efficient and highly specific way to inhibit
      viral replication in vivo and disease progression in the hosts.

PMID- 16454704
TI  - Bacterial sepsis and chemokines.
AB  - Bacterial sepsis causes a high mortality rate when it occurs in patients with
      compromised host defenses. Severely burned patients, typical immunocompromised
      hosts, are extremely susceptible to infections from various pathogens, and a
      local wound infection frequently escalates into sepsis. In these patients,
      Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa are
      familiar pathogens that cause opportunistic infections. Also, polymicrobial
      sepsis frequently occurs in these patients. In this review, therefore, the roles
      of chemokines in thermally injured patients infected with these 3 pathogens and
      polymicrobial sepsis will be discussed. These infections in thermally injured
      patients may be controlled immunologically, because immunocompetent hosts are
      resistant to infections with these pathogens. Classically activated macrophages
      (M1Mphi) are major effector cells for host innate immune responses against these
      infections. However, M1Mphi are not generated in thermally injured patients whose
      alternatively activated macrophages (M2Mphi) predominate. M2Mphi appear in
      patients early after severe burn injuries. M2Mphi inhibit M1Mphi generation
      through the secretion of CCL17 and IL-10. As a modulator of Mphi, two different
      subsets of neutrophils (PMN-I, PMN-II) are described. PMN-I direct the
      polarization of resident Mphi into M1Mphi through the production of CCL3. M2Mphi
      are induced from resident Mphi by CCL2 released from PMN-II. Therefore, as an
      inhibitor of CCL2, glycyrrhizin protects individuals infected with S. aureus.
      Sepsis stemming from P. aeruginosa wound infection is also influenced by CCL2
      released from immature myeloid cells. A large number of immature myeloid cells
      appear in association with burn injuries. Host resistance to S. aureus, E.
      faecalis, P. aeruginosa or polymicrobial infections may be improved in thermally
      injured patients through the induction of M1Mphi, elimination of CCL2 and/or
      depletion of M2Mphi induced by CCL2.

PMID- 16454705
TI  - The chemokine network as therapeutic target in human diseases.

PMID- 16454707
TI  - Affordable antiretroviral drugs for the under-served markets: how to expand
      equitable access against the backdrop of challenging scenarios?
AB  - BACKGROUND: Threats by enforced Intellectual Property (IP) rights to equitable
      HIV treatment access by poor populations are impending. India and China's policy
      directions in the field will be crucial in ultimately affecting the affordability
      and accessibility of antiretroviral (ARV) therapy in the under-served markets.
      These directions, together with the exploitation level of IP-bound flexibilities
      and the evolutionary modelling in partnerships and trade agreements between
      research-based and generic pharmaceutical industry, will also affect the outcomes
      of self-sufficiency efforts now at their beginning in the developing world as far
      as domestic manufacturing of generic ARV drugs is concerned. AIMS: This paper
      explores key issues, implications and interaction dynamics across these
      challenging scenarios while attempting to provide equitable solution glimpses
      into the near future. RESULTS: Access-oriented long-term drug policy strategies
      entitled to pass muster of governments, research-based as well as generic
      industries in both developed and developing countries are needed if equitable
      access to affordable ARV treatments by poor people has to be achieved despite
      enforced IP rights. Predictable dynamics between western multinationals and
      transitional country generic corporations let regard IP-bound Voluntary License
      flexibilities as a fitting measure into just mentioned needs especially if
      substantial incentives to generic corporations are concurrently secured. Efforts
      to equitably expand ARV drug access through exploiting IP opportunities should
      encompass attainment of self-sufficiency in domestic drug manufacturing whenever
      basic requirements are in place in the developing world as a whole. A credible
      industrial potential would act, indeed, as a boosting factor for drawing branded
      drug producers into technology transfer agreements, the terms of which would let
      all contractors enjoy substantial advantages. These perspectives consistently
      bind up with the foreseeable long-term trade and drug policy directions of India
      and China according to frontier crossing implications of their key IP management
      trends as well as their multifaceted penetration strategies of both the wealthy
      and under-served markets worldwide. As coherent with these perspectives, more
      disbursement by wealthy country governments and donors to basic infrastructure
      development in sub-Saharan African nations with stable governments in place is
      urged both as a priority for improving Africa's economy and a prerequisite for
      allowing domestic industrial plants to take off. Aiming at the targets just
      underscored, WHO's brokering role in negotiated agreements between wealthy and
      developing country-based firms as well as its technical guidance in setting
      international standards have always to be sought if equitable and appropriate end
      results are to be attained. CONCLUSION: Overall insights in this paper would mean
      that, while research-based corporations are to be praised whenever waiving, on
      humanitarian purposes, part of their profits, the trade and profit rules cannot
      basically be given up if long-term sustainable results are the goal to look for.
      Only negotiated agreements securing all contracting parties lasting advantages
      may ensure shifting of such a goal from mere vision to a really sustainable
      attainment.

PMID- 16454708
TI  - Understanding human immunodeficiency virus type 1 and hepatitis C virus
      coinfection.
AB  - In recent years, there has been an alarming increase in the number of cases of
      coinfection with the human immunodeficiency virus type 1 (HIV-1) and the
      hepatitis C virus (HCV). It is now known that coinfection of HIV-1 patients by
      HCV can complicate the treatment of these patients with highly active
      antiretroviral therapy and the interactions between anti-HIV-1 and anti-HCV
      medications can also affect treatment efficacy and efficiency. Equally
      concerning, the bidirectional interferences between the two viruses are complex
      and can modify the natural history of both infections. This review aims to
      summarize the findings of numerous scientific investigations in the area of
      HIV/HCV coinfection. These investigations can be broadly classified into 3
      groups; (a) immune evasion mechanisms (b) viral evolution and quasispecies
      diversity and (c) functions of viral proteins and their interactions with host
      factors. Our cumulative knowledge in this area and future research on the
      interplay between these two viruses will be important to the development of
      better antiviral therapeutics.

PMID- 16454709
TI  - Uracils as a cellular weapon against viruses and mechanisms of viral escape.
AB  - Uracil in DNA is a deleterious event that may arise either by cytosine
      deamination or misincorporation of dUTP. Consequently, cells from all free-living
      organisms have developed strategies to protect their genome against the presence
      of uracils, by using uracil DNA glycosylase (UNG) and deoxyuridine triphosphatase
      (dUTPase) enzymatic activities. In the viral kingdom, some (namely poxviruses and
      herpesviruses) but not all of the DNA viruses encode their own UNG and dUTPase to
      control uracilation of their genome. Some retroviruses, which are RNA viruses
      using DNA as an intermediate of replication, also encode dUTPase. Surprisingly,
      though most of nonprimate lentiviruses encode dUTPase, primate lentiviruses such
      as HIV-1, HIV-2 or SIV do not. Because these latter viruses also replicate in
      nondividing cells where the dUTP/dTTP ratio is high, it is probable that they
      have found other ways to fight against the emergence of uracilated-viral
      transcripts. Indeed, recent studies showed that HIV-1 efficiently controls both
      the cytosine deamination and the dUTP misincorporation. The viral Vif protein
      acts in preventing the packaging into viral particles of the host-derived
      cytosine deaminase APOBEC3G enzyme, while the viral integrase domain of the Gag
      Pol precursor mediates the packaging of the host-derived uracil DNA glycosylase
      UNG2 enzyme. In the absence of Vif or UNG2, HIV-1 viral transcripts are heavily
      charged in uracil bases leading to inactivation of the virus.

PMID- 16454710
TI  - Role of viral splicing elements and cellular RNA binding proteins in regulation
      of HIV-1 alternative RNA splicing.
AB  - In HIV-1 infected cells, over 40 different mRNA species are produced by
      alternative splicing of the single HIV-1 primary RNA transcript. In addition,
      approximately half of the HIV-1 primary RNA transcripts are not spliced and are
      exported to the cytoplasm where they serve as mRNA and as genomic RNA. In this
      article, we will review current knowledge of the mechanisms by which the HIV-1
      alternative splicing is regulated. Several negatively and positively-acting cis
      acting elements have been detected within the viral genome that repress or
      facilitate viral RNA splicing by binding to cellular proteins. These include
      exonic splicing silencers (ESS) and an intronic splicing silencer (ISS) that are
      selectively bound either by members of the hnRNP A/B family (hnRNPs A1, A1(B),
      A2, and B1) or by hnRNP H. Exonic splicing enhancers (ESE) are also present
      within the HIV-1 genome and are selectively bound by members of the SR protein
      family. ESS and ISS repression mediated by hnRNP A/B proteins occurs at early
      steps of splicing, prior to formation of pre-spliceosome complexes. Current
      models propose that ESS elements promote cooperative binding of hnRNP A/B
      proteins to the exon and prevent efficient binding of essential cellular splicing
      factors to the 3' splice site. SR proteins bound to ESE elements that are
      juxtaposed or overlapping ESS elements may counteract this inhibition. We will
      review data indicating the importance of the HIV-1 splicing elements and their
      cognate binding proteins for efficient virus replication. Differences in cis
      acting splicing elements between the group M (major) and group O (outlier) HIV-1
      strains will also be discussed. Finally we will review evidence suggesting the
      possibility that there may be changes in regulation of HIV-1 alternative splicing
      in infected human T cells, human macrophages and rodent cells.

PMID- 16454711
TI  - Modelling thymic HIV-1 Nef effects.
AB  - The nef gene is conserved among primate lentiviruses and is one of the first
      viral genes that is transcribed following infection. This suggests a critical
      role for Nef in the virus life cycle and in the pathogenesis of lentiviral
      infections. In vitro, several functions have been described, including down
      regulation of CD4 and MHC class I surface expression, altered T-cell signaling
      and activation, and enhanced viral infectivity. However, the impact of these
      individual functions on viral pathogenicity in general, and thymic T cell
      production in particular, remains elusive. Here, we review the observations from
      experimental models that have been used to study the pathogenic effect of HIV-1
      Nef on the thymus. These in vitro and in vivo studies have led to a better
      understanding of Nef's mechanism of action, although there still exists discord
      as to the contribution of Nef-mediated disturbance of thymopoiesis in the
      pathogenesis of AIDS.

PMID- 16454712
TI  - HIV-1 fitness and disease progression: insights from the SIV-macaque model.
AB  - Within the initial weeks following transmission, HIV-1 becomes well established
      in the lymphatic tissue reservoir. Replication of the virus occurs throughout the
      course of infection despite the induction of a vigorous adaptive immune response
      by the host. The emergence of variants with particular characteristics correlates
      with increased viral burden and disease progression, indicating that the fitness
      of the infecting virus and selected variants plays a significant role in
      persistent viral replication and disease progression. This article reviews
      studies of HIV-1 variants and pathogenicity. It focuses mainly on experimental
      SIV infection of macaques as a model system to decipher the significance of viral
      variants for infection, persistence, and disease because it is difficult to
      systematically examine transmission and pathogenesis of HIV-1 in humans.

PMID- 16454713
TI  - Metabolic and cardiovascular complications of highly active antiretroviral
      therapy for HIV infection.
AB  - Highly active antiretroviral therapy (HAART) regimens, especially those including
      protease inhibitors have been shown to cause, in a high proportion of HIV
      infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia,
      type 2 diabetes mellitus, insulin resistance) that may be associated with an
      increased risk of cardiovascular disease. A careful stratification of the
      cardiovascular risk of HIV-infected patients under HAART is needed according to
      the most recent clinical guidelines.

PMID- 16454714
TI  - Intestinal parasite infestation in HIV infected patients.
AB  - One of the major health problems among HIV-infected patients is the intestinal
      parasite infestations. It can be seen that intestinal helminth infestation in HIV
      infected patients is common. However, the reported prevalence is usually similar
      to those of non HIV-infected patients in the same setting. The infestations are
      ordinary not opportunistic, hence, thus usually show no correlation to immune
      status of the patients. The suppression of immunity due to HIV infection shows no
      significant role in increasing the intestinal helminth infestations. On the other
      hand, having occult intestinal helminth infestations does also not worsen the
      outcome of HIV infection. Concerning the clinical manifestation, most of the
      helminth infestations are asymptomatic and the diagnosis is usually based on the
      stool examination. Treatments of the infestations as well as the outcomes are
      usually similar to immunocompetent host. Intestinal protozoa infestations are
      also important problems for HIV-infected patients. Some infections are ordinary,
      while the others are opportunistic infection. The important opportunistic
      intestinal parasites including C. parvum, I. belli, Cyclospora and the
      Microsporidia are found at high prevalence among the HIV-infected patients,
      especially in low immune cases with persistent diarrhea. Concerning the clinical
      manifestation, most of the infestations bring diarrhea and the diagnosis is
      usually based on the stool examination with special stains. The treatment of the
      opportunistic infection can usually get control of the present illness but not
      prevent the re-infection. Luckily, with the present wide distribution of HAART,
      the prevalence of the opportunistic intestinal protozoa infections is
      significantly decreased.

PMID- 16454715
TI  - Diabetes case identification methods applied to electronic medical record
      systems: their use in HIV-infected patients.
AB  - OBJECTIVE: New onset diabetes mellitus type 2 is increasing among HIV-infected
      patients in the era of potent antiretroviral therapy. Accurately identifying HIV
      infected patients with a diagnosis of diabetes in electronic medical record
      systems will facilitate the study of patients with this disease. STUDY DESIGN AND
      SETTING: We examined electronic medical record data for all patients who
      initiated care at an HIV clinic between 1/1/1997 and 12/31/2001 to identify
      potential cases of diabetes. Case identification methods included clinician-coded
      diagnoses, medications, and HbA1c and glucose levels. Diabetes diagnoses were
      verified by clinician documentation in an electronic medical record progress
      note. Test characteristics of each case identification method were calculated.
      RESULTS: 53 cases of diabetes were identified among the cohort of 1,441 patients.
      Use of clinician-coded diagnoses alone or combined with other methods was the
      most sensitive method for identifying diabetes cases. Clinician-coded diagnoses
      were also the best method as assessed by standard receiver operator
      characteristic plots. A significant attenuation of odds ratios for associations
      with diabetes were found for case identification methods with imperfect
      specificity such as serum glucose levels. CONCLUSIONS: This study demonstrates
      that electronic medical record data can be used to accurately identify HIV
      infected patients with diabetes. The optimal method applied will depend on the
      goals of a particular study.

PMID- 16454716
TI  - Thrombocytopenia in HIV infection: impairment of platelet formation and loss
      correlates with increased c-Mpl and ligand thrombopoietin expression.
AB  - Thrombocytopenia is a common hematologic disorder in patients infected with the
      human immunodeficiency virus (HIV) and represents a risk for bleeding which is
      further deleterious during surgery. The major causes of the thrombocytopenia
      include accelerated peripheral platelet destruction by antiplatelet antibodies
      and insufficient production of platelets from the infected megakaryocytes.
      Additionally, at an earlier stage of platelet development, HIV may inhibit
      megakaryopoiesis at multiple stages of pluripotent CD34+ progenitor stem cell
      differentiation possibly contributing to decreased levels of platelets in
      circulation. In HIV infected patients, both the serum thrombopoietin (TPO) levels
      and theTPO-c-Mpl complexes on the platelet surface were significantly elevated.
      Therapeutic infusion of HIV infected patients with pegylated recombinant human
      megakaryocyte growth development factor (PEG-rHu-MGDF) restores platelet counts
      to normal levels and reduces the c-Mpl expression per platelet. In vitro
      aggregation of platelets treated with TPO and agonist, adenosine diphosphate
      (ADP), decrease the dose of ADP that is required for half-maximum aggregation. In
      vivo dosing does not effect platelet aggregation showing that the metabolism of
      TPO following its internalization through TPO-c-Mpl complex is rapid and that
      dosing within the therapeutic range does not constitute increased risk of
      thrombotic disease.

PMID- 16454718
TI  - Fibromyalgia syndrome: which antidepressant drug should we choose.
AB  - Fibromyalgia syndrome [FM] has core clinical features of widespread pain and
      widespread abnormal tenderness. The specific cause of the altered neurophysiology
      that underpins these clinical manifestations remains unclear. However, increased
      sensitisation of neural networks that relates to pain, as well as interacting
      mechanoreceptors, appear important targets for modulation by pharmacological
      agents. Further, many FM patients have emotional distress and some are depressed.
      Antidepressant agents have therapeutic benefits in FM. If depression is present
      antidepressant drugs will provide typical benefits to mood but not always to
      other key outcome measures, such as pain or tenderness. Selective serotonin
      receptor reuptake blockers are not as effective for overall FM improvement as
      drugs that block both serotonin and norepinephrine in a relatively balanced way.
      Thus tricyclic antidepressants will improve many important FM outcomes but are
      effective in only about 40 percent of individuals. Newer agents of this class,
      such as duloxetine and milnacipran, show improvement in key FM outcomes in about
      60 percent of patients. Longer term studies will indicate the durability of these
      responses and the overall tolerance of the drugs. Any drug therapy will need to
      be integrated with appropriate education, exercise and attention to psychological
      modulatory factors to achieve best results.

PMID- 16454719
TI  - Combination therapy in fibromyalgia.
AB  - Fibromyalgia is an enigmatic medical condition whose specific etiology remains
      undiscovered but currently plagues five million Americans. Research indicates
      that the origin of the disease is most likely multifactorial. Treatment should
      therefore be tailored accordingly. Thus, it is often necessary to combine
      different options in order to achieve the maximum benefit in patients suffering
      from fibromyalgia.

PMID- 16454720
TI  - Is there a role for cytokine based therapies in fibromyalgia.
AB  - Cytokines are glycoproteins that serve as chemical messengers between cells. They
      assist in the regulation of cell growth and repair and also have immune
      modulating properties. Cytokines play a role in diverse clinical processes and
      phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the
      fibromyalgia literature and related studies suggest that IL-1, IL-6 and IL-8 are
      dysregulated in the syndrome. Therapies directed against these cytokines may be
      of potential importance in the management of fibromyalgia.

PMID- 16454721
TI  - Are tender point injections beneficial: the role of tonic nociception in
      fibromyalgia.
AB  - Characteristic symptoms of fibromyalgia syndrome (FM) include widespread pain,
      fatigue, sleep abnormalities, and distress. FM patients show psychophysical
      evidence for mechanical, thermal, and electrical hyperalgesia. To fulfill FM
      criteria, the mechanical hyperalgesia needs to be widespread and present in at
      least 11 out of 18 well-defined body areas (tender points). Peripheral and
      central abnormalities of nociception have been described in FM and these changes
      may be relevant for the increased pain experienced by these patients. Important
      nociceptor systems in the skin and muscle seem to undergo profound changes in FM
      patients by yet unknown mechanisms. These changes may result from the release of
      algesic substances after muscle or other soft tissue injury. These pain mediators
      can sensitize important nociceptor systems, including the transient receptor
      potential channel, vanilloid subfamily member 1 (TRPV1), acid sensing ion channel
      (ASIC) receptors, and purino-receptors (P2X3). Subsequently, tissue mediators of
      inflammation and nerve growth factors can excite these receptors and cause
      substantial changes in pain sensitivity. FM pain is widespread and does not seem
      to be restricted to tender points (TP). It frequently comprises multiple areas of
      deep tissue pain (trigger points) with adjacent much larger areas of referred
      pain. Analgesia of areas of extensive nociceptive input has been found to provide
      often long lasting local as well as general pain relief. Thus interventions aimed
      at reducing local FM pain seem to be effective but need to focus less on tender
      points but more on trigger points (TrP) and other body areas of heightened pain
      and inflammation.

PMID- 16454722
TI  - Physical therapy modalities in management of fibromyalgia.
AB  - The etiology of fibromyalgia syndrome (FM) is uncertain and the prognosis for
      symptomatic recovery is generally poor. A wide variety of interventions are used
      in the management of FM. There is, however, no clear consensus on the treatment
      of choice and FM remains relatively refractory to treatment. Therefore,
      prevention, causal therapy and rehabilitation are not possible. FM patients
      frequently use alternative therapies, indicating dissatisfaction or
      ineffectiveness of traditional medical therapy. Alternative therapies are
      generally perceived to be more "natural" and as a result, to have fewer adverse
      effects. Despite the positive results found, the number of publications related
      to the application of physical therapy modalities such as acupuncture,
      transcutaneous electrical stimulation, laser, biofeedback, electrotherapy and
      magnetic field is still scant, especially concerning FM treatment. The
      demonstration of a long-term effective intervention for managing the symptoms
      associated with FM is needed. Multidisciplinary approaches to management include
      physical and medical therapeutic strategies. Treatment modalities should be
      individualised for patients based on target symptoms and impairment in
      functioning. Patience and positive attitude on part of the physician and active
      involvement of patients and their families in treatment are likely to enhance
      improvement. It can be concluded that there is a need for larger, more systematic
      and methodologically sound randomised controlled clinical trials to evaluate the
      effectiveness of physical therapy modalities of managing FM. We will review some
      of the existing studies of physical therapy relevant in the treatment of FM and
      give some practical advice for their use.

PMID- 16454723
TI  - Exercise and cognitive-behavioural treatment in fibromyalgia syndrome.
AB  - Fibromyalgia syndrome is a nonarticular rheumatic disorder characterised by
      diffuse musculoskeletal pain, stiffness, fatigue, disturbed sleep and tender
      points. The pathophysiology is not well understood and treatment remains a
      challenge. Although pharmacological therapy is still the primary treatment
      choice, a long-term effective intervention has not been demonstrated yet. Thus,
      besides pharmacotherapy, other multimodal interventions are often used. Exercise
      and cognitive-behavioural treatments which exist in the multimodal approach and
      encompass largely self-managed strategy, are reviewed in this article. Although,
      there is a great number of exercise studies, the large diversity of outcome
      measures and measurement instruments that have been used in studies, varying
      intensity and types of exercises, small sample sizes, high attrition rates, large
      variability in baseline function, symptom severity and psychosocial status limit
      to come to a conclusion about the efficacy of exercise in the treatment of
      fibromyalgia syndrome. There are also inconclusive results about the efficacy of
      cognitive-behavioural treatment because of limited number of studies with small
      sample sizes of patients with fibromyalgia syndrome. However, the results of the
      trials overall demonstrate the beneficial effects of both different types of
      exercise and cognitive-behavioural treatment, on the other hand, there is still a
      need for larger, more systematic and randomised controlled trials to evaluate the
      effectiveness.

PMID- 16454724
TI  - Complementary and alternative medical therapies in fibromyalgia.
AB  - This article describes the studies that have been performed evaluating
      complementary or alternative medical (CAM) therapies for efficacy and some
      adverse events fibromyalgia (FM). There is no permanent cure for FM; therefore,
      adequate symptom control should be goal of treatment. Clinicians can choose from
      a variety of pharmacologic and nonpharmacologic modalities. Unfortunately,
      controlled studies of most current treatments have failed to demonstrate
      sustained, clinically significant responses. CAM has gained increasing
      popularity, particularly among individuals with FM for which traditional medicine
      has generally been ineffective. Some herbal and nutritional supplements
      (magnesium, S- adenosylmethionine) and massage therapy have the best evidence for
      effectiveness with FM. Other CAM therapies such as chlorella, biofeedback,
      relaxation have either been evaluated in only one randomised controlled trials
      (RCT) with positive results, in multiple RCTs with mixed results (magnet
      therapies) or have positive results from studies with methodological flaws
      (homeopathy, botanical oils, balneotherapy, anthocyanidins and dietary
      modifications). Another CAM therapy such as chiropractic care has neither well
      designed studies nor positive results and is not currently recommended for FM
      treatment. Once CAM therapies have been better evaluated for safety and long-term
      efficacy in randomised, placebo-controlled trials, they may prove to be
      beneficial in treatments for FM. It would then be important to assess studies
      assessing cost-benefit analyses comparing conventional therapies and CAM.

PMID- 16454725
TI  - Multidisciplinary approaches for management of fibromyalgia.
AB  - Multidisciplinary approaches to fibromyalgia syndrome (FMS) treatment are
      advocated for treating the complex symptoms and problems confronting many
      patients. Exercise and cognitive-behavioral strategies together with patient
      education commonly comprise the multidisciplinary approach to treatment in
      clinical trials. A review of the research literature suggests that they are
      effective for decreasing pain and FMS impact and increasing self-efficacy and
      physical functioning. Limitations of the current evidence base include a lack of
      studies that include medication treatment as part of the multidisciplinary
      approach as well as lack of attention to the diversity of patient psychosocial
      issues that may interfere with treatment effectiveness. The review recommends
      that further randomized clinical trials be carried out with subgroups of patients
      using standardized outcome measurements, adequate treatment length and sufficient
      length of follow-up to be able to observe and document changes in patient
      symptoms and behaviors over time.

PMID- 16454726
TI  - New strategies in evaluation of therapeutic efficacy in fibromyalgia syndrome.
AB  - Fibromyalgia (FM) is continuing to be a challenging and confusing disorder for
      researchers and clinicians with its diverse symptoms, poorly understood etiology
      and pathophysiology. The use of multiple outcome variables reflecting the
      complexity of FM and co-morbid syndromes, makes it difficult to evaluate the
      efficacy or effectiveness of the treatment in clinical trials. Additionally
      researchers inevitably rely on patients' self-reported outcome data, which is
      prone to error and bias. In this paper, new researches in the field of FM and
      practical issues on methodology of pain assessment (visual analogue scales, paper
      or electronic diaries and compliance), core outcome domains in chronic pain
      assessment (IMMPACT recommendations), and advances in neuroimaging techniques
      like functional magnetic resonance imaging have been reviewed. Consequently,
      clinicians and researchers have various highly validated and adequate outcome
      domains to assess FM symptoms and new researches continue to add new valuable
      domains. Nevertheless the current problem is to conclude, which treatment works
      best for whom and which are the outcome domains suitable for FM patients or
      patients' subgroups with different prominent features. Standardised and
      appropriate core outcome domains for FM clinical trails will encourage more
      complete investigations, relevant outcome reporting and well-designed multicenter
      trials.

PMID- 16454728
TI  - PPAR-gamma agonists as regulators of microglial activation and brain
      inflammation.
AB  - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) belongs to a
      large group of nuclear receptors controlling reproduction, metabolism,
      development and immune response. Upon activation by specific agonists, these
      receptors form dimers and translocate to the nucleus, where they act as agonist
      dependent transcription factors and regulate gene expression by binding to
      specific promoter regions of target genes. The observation that PPAR-gamma is
      involved in the regulation of macrophage differentiation and activation in the
      peripheral organs has prompted the investigation of the functional role of PPAR
      gamma in microglial cells, the main macrophage population of the CNS. The present
      review summarizes the several lines of evidence supporting that PPAR-gamma
      natural and synthetic agonists may control brain inflammation by inhibiting
      several functions associated to microglial activation, such as the expression of
      surface antigens and the synthesis of nitric oxide, prostaglandins, inflammatory
      cytokines and chemokines. Moreover, one of the major natural PPAR-gamma agonist,
      15d-prostaglandin J(2) may contribute to the safe elimination of activated
      microglia by inducing apoptosis. Synthetic PPAR-gamma agonists do not entirely
      reproduce the range of 15d-prostaglandin J(2) effects, suggesting that PPAR-gamma
      independent mechanisms are also involved in the action of this prostaglandin. In
      addition to microglia, PPAR-gamma agonists affect functions and survival of other
      neural cells, including astrocytes, oligodendrocytes and neurons. Although most
      of the evidence comes from in vitro observations, an increasing number of studies
      in animal models further supports the potential therapeutic use of PPAR-gamma
      agonists in human brain diseases including multiple sclerosis, Parkinson's
      disease and Alzheimer's disease.

PMID- 16454727
TI  - Metabolism-directed optimisation of antithrombotics: the prodrug principle.
AB  - Thromboembolic disorders are the major cause of mortality and morbidity in
      Western societies. Coagulation enzymes, such as thrombin, factor Xa and a tissue
      factor/factor VIIa complex, together with platelet GPIIb/IIIa receptors, are the
      focal point of attention in pharmaceutical research aimed at finding new
      antithrombotic agents. However, finding orally active drugs for these particular
      molecular targets has proved to be anything but straightforward. Thrombin, factor
      Xa, tissue factor/factor VIIa and platelet GPIIb/IIIa receptors display a
      preference for molecules containing highly basic arginine and/or acidic aspartate
      moieties, which are, however, associated with poor bioavailability after oral
      application. Different approaches have been taken to achieve favourable
      absorption, metabolism, distribution and clearance, without compromising the
      antithrombotic activity of the compounds. This review highlights the use of the
      prodrug principle in optimising antithrombotic agents.

PMID- 16454729
TI  - Novel agents aiming at specific molecular targets increase chemosensitivity and
      overcome chemoresistance in hematopoietic malignancies.
AB  - In hematologic neoplasias primary or secondary resistance of malignant cells
      towards the applied treatment presents the major clinical obstacle in the
      induction of remission and definite cure. Evaluation of the underlying molecular
      mechanisms determining response or resistance not only enables the clinician to
      define prognostic markers, but moreover facilitates the design of molecularly
      targeted agents potentially reversing the causative lesion. Deregulation of
      apoptosis is considered to contribute to the emergence and propagation of the
      malignant clone, and several molecular alterations hindering programmed cell
      death and thus leading to chemoresistance have been defined. While reviewing
      these molecular alterations this article moreover focuses on the impact of new
      therapeutic agents, which specifically exploit the knowledge of the molecular
      characteristics of malignant hematopoetic cells.

PMID- 16454731
TI  - The dendritic cell-T cell synapse as a determinant of autoimmune pathogenesis.
AB  - Autoimmune diseases occur when the immune response is targeted to self-antigens,
      leading to destruction or altered function of specific cells and tissues.
      Although the aetiology of these diseases has not yet been fully elucidated, it is
      believed that genetically determined susceptibility and environmental triggers
      are both implicated in the detrimental immune response against the body's own
      tissues. Dendritic cells (DCs) are professional antigen presenting cells that
      play an important role in maintaining peripheral tolerance by preventing self
      reactive T cells from causing autoimmune damage. Thus, alterations in the
      physiology of DCs are likely to be responsible for defective immune regulatory
      mechanisms and incomplete tolerance to self. Here, we will focus specifically on
      the ways in which the immunological synapse occurring at the DC-T cell interface
      can fine-tune the balance between tolerance and immunity and how alterations of
      this synapse can determine induction or perpetuation of autoimmune responses.
      Activating/inhibitory receptors expressed on the surface of DCs and T cells
      modulate the function of these cells and influence the course of the immune
      response. Pharmacological approaches that can modulate DC function will be also
      addressed as a potential antigen-specific strategy in the design of new,
      noninvasive therapies to prevent or to treat chronic inflammatory autoimmune
      disorders.

PMID- 16454732
TI  - Mechanisms of CTLA-4-Ig in tolerance induction.
AB  - The size of the peripheral T lymphocyte pool remains relatively constant
      throughout adult life, but individual populations undergo expansion and
      contraction upon antigen encounter due to signals delivered by members of the B7
      CD28 family of costimulatory molecules. This family includes receptors on T cells
      that can provide either activating or inhibitory signals. In general, activation
      occurs in response to pathogens, when lymphocyte expansion and acquisition of
      effector functions is appropriate. Conversely inhibitory receptors provide down
      modulating signals that help terminate immune responses and maintain self
      tolerance. The activating receptor CD28 engages the same B7-1 and B7-2 molecules
      as the inhibitory receptor cytotoxic T lymphocyte antigen 4 (CTLA-4), although
      with reduced affinity than CTLA-4. In addition to this direct competitive
      mechanism, CTLA-4 can directly inhibit T cell receptor (TCR) signals
      independently of CD28 expression and recent findings indicate that CTLA-4 may
      also operate through reverse signaling on ligand-expressing cells. Fusion
      proteins between the extracellular domain of CTLA-4 and an immunoglobulin Fc
      portion have been created that have potent immunosuppressive properties in animal
      models of transplantation and autoimmunity and that show great promise in
      clinical trials. Like CTLA-4, CTLA-Ig, is thought to selectively prevent
      activation of CD28 by interacting with B7-1 and B7-2. In addition, CTLA-4-Ig can
      bind to B7 molecules expressed on dendritic cells and activate a pathway of
      tryptophan catabolism that can lead to indirect inhibition of lymphocyte
      activation and T cell death. In this review, we will focus on the current
      knowledge of the mechanisms of action of CTLA-4 and CTLA-4-Ig.

PMID- 16454734
TI  - Autoantibody-induced formation of immune complexes in normal human serum.
AB  - Intravenous immunoglobulins (IVIg) are concentrated preparations of purified
      human plasma-derived IgG routinely used in the treatment of many autoimmune
      diseases. Their precise mechanisms of therapeutic action have remained unclear in
      most diseases and are attracting much interest due to the rapidly increasing use
      of this precious plasma-derived product. The presence in IVIg of IgG reactive
      with various human structures has been known for many years. In this review, we
      first briefly discuss the formation and role of natural autoreactive human IgG in
      healthy individuals. A role for IgG autoantibodies in the in vivo
      immunomodulatory effects of IVIg has been proposed several years ago but the
      underlying mechanism has remained unclear. Recent work has shown that the large
      IVIg doses infused in many patients could oversaturate the normal anti-idiotype
      dependent inhibition of autoreactive IgG present in the plasma of all healthy
      individuals since the formation of autoimmune complexes could be observed in
      normal serum in presence of therapeutic amounts of IVIg. These autoimmune
      complexes could have potent in vivo immunomodulatory effects by interacting with
      various IgG and complement receptors. Furthermore the autoreactive IgG can be
      easily purified from IVIg by affinity chromatography, raising the interesting
      possibility of further fractionating IVIg into different sub-products for use in
      the treatment of different diseases. These results indicate that natural
      autoantibodies have important in vivo roles not only for the protection of the
      body against infectious agents but also for the efficiency of passive
      immunotherapy procedures used in the treatment of many diseases.

PMID- 16454733
TI  - Lysophospholipid receptors as potential drug targets in tissue transplantation
      and autoimmune diseases.
AB  - New therapies directed at ameliorating or altering autoimmune diseases represent
      an area of significant medical need. Included amongst autoimmune diseases are
      problems related to transplantation rejection, as well as a number of
      neurological diseases such as Multiple Sclerosis (MS). A new group of molecular
      targets that may lead to novel therapies are lysophospholipid (LP) receptors. A
      large range of biological activities has been attributed to the actions of these
      simple phospholipids that include well-studied members lysophosphatidic acid
      (LPA) and sphingosine 1-phosphate (S1P). Documented cellular effects of these
      lipid molecules encompass growth-factor-like influences on cells, including but
      not limited to survival, migration, adhesion differentiation, as well as
      pathophysiological actions associated with cancer. In turn, these cellular
      effects have roles in developing and adult organ systems such as the nervous
      system, cardiovascular system, reproductive system and, of relevance here, the
      immune system. The mechanisms for these actions can be attributed to a growing
      family of cognate, 7-transmembrane G protein-coupled receptors (GPCRs), with
      documented validation through studies utilizing pharmacology, molecular genetics
      and an enlarging repertoire of chemical tools having agonist or antagonist
      properties. The growing literature on immunological effects of LP receptors,
      particularly those mediating the effects of S1P, has suggested possible
      therapeutic roles for this class of receptors. In particular, entry into humans
      of a non-selective S1P receptor agonist, FTY720, for kidney transplantation and
      possibly other indications (e.g., Multiple Sclerosis), has raised prospects for
      efficacious treatment of human diseases based on LP receptor targets. Here we
      provide a brief introduction to receptor-mediated lysophospholipid signaling and
      discuss its basic and potential therapeutic roles in autoimmune-related diseases.

PMID- 16454735
TI  - IgG dimers in multidonor-derived immunoglobulins: aspects of generation and
      function.
AB  - Immunoglobulin G (IgG) concentrates for therapeutic purposes, like passive
      immunotherapy, supplementation in inherited or acquired deficiencies or
      immunomodulation, are prepared from multidonor-derived plasma pools. They usually
      contain varying amounts of dimeric IgG. The essential factor influencing dimer
      formation is the pool size; in addition, molecular properties of IgG and a
      variety of production process- and formulation-specific parameters are important.
      Numerous experimental findings suggest that dimers are predominantly generated by
      interactions of idiotypic and anti-idiotypic antibodies (Ids, anti-Ids). Ab
      inherent crossreactivity, frequency distribution of both the affinities for
      particular Id-anti-Id interactions and the corresponding dimer concentrations
      still have to be elucidated. All these parameters influencing molecular features
      and functional activity of IgG dimers hamper the assay-dependent measurement of
      biological efficacy and correlation of total IgG content. A more detailed
      understanding may help to better control the dual nature of dimer-dependent
      biological activity comprising both undesirable (e.g., hypotension) and desirable
      effects of dimeric IgG (blockade of the reticuloendothelial system, RES, in
      immune thrombocytopenic purpura, ITP). These effects are detectable in in vitro
      and in vivo models and are thought to be of relevance for humans.

PMID- 16454736
TI  - Antibody-like peptides as a novel purification tool for drugs design.
AB  - New pharmaceutical approaches, such as biotechnology industry, genomic and
      proteomic studies, require the development of new analytical and preparative
      tools that should allow the resolution and the characterisation of complex sets
      of molecule mixtures in a high-throughput mode with the isolation of a single
      substance from complex matrices in a high degree of purity, low costs and wide
      availability. In this review we discuss the design of a tailor-made peptide by
      focusing our attention on the bioinformatic techniques and combinatorial
      approaches. Then synthesis, purification and characterisation of peptides with
      recognition properties are discussed by considering different approaches and
      their fitness to drug design. Moreover, the development of affinity devices and
      the discussion of their characteristics to optimise the purification phase are
      reported. Applications of peptide ligands that bind pharmaceutical compounds
      (i.e. therapeutic proteins, monoclonal antibodies, hormones) are described and
      analytical tools mentioned and evaluated. Future perspectives, in particular
      alternative applications of peptide ligands and their substitution with
      peptidomimetic compounds, are described.

PMID- 16454737
TI  - Cyclooxygenases regulation by estradiol on endothelium.
AB  - Estrogen and hormone replacement therapies are being tested to prevent the
      incidence of cardiovascular disease in postmenopausal women. In spite of the
      evidence from several epidemiological studies suggesting that estrogens protect
      against atherosclerosis and associated diseases, controversy exists. Moreover, it
      is important to develop synthetic compounds that achieve the beneficial effects
      of estrogens on the cardiovascular system while minimizing such undesirable
      effects on other tissues as the increased risk of endometrial and breast cancer.
      Some drugs that modulate estrogen function in a tissue-specific manner (Selective
      Estrogen Receptor Modulators; SERMs) have been discovered and are currently being
      used in clinical practice. An example of these is raloxifene. Clinical and
      experimental data support the consideration of endothelium as a target for
      estradiol and other sexual hormones. Among other actions, estradiol has been
      implicated in the control of prostacyclin production through cyclooxygenases
      (COX) regulation in endothelial cells. Prostacyclins are powerful vasodilators
      and potent inhibitors of platelet aggregation which are produced from free
      arachidonic acid through the catalytic activity of two COX: COX-1 and COX-2.
      Together, these COX represent the main control mechanism for prostacyclin
      production. Although several non-specific COX inhibitors have been available for
      decades (aspirin, indomethacin, ibuprofen), COX-2 selective inhibitors have been
      commercialized only within the last few years, thus making it possible to
      increase the study and treatment of different disorders. This review will discuss
      clinical and experimental data that document the endothelial effects of estradiol
      and SERMs on prostacyclin production and COX regulation, their vascular
      consequences, and their possible interactions with COX inhibitors.

PMID- 16454738
TI  - The peripheral anionic site of acetylcholinesterase: structure, functions and
      potential role in rational drug design.
AB  - The peripheral anionic site of acetylcholinesterase lies at the entrance to the
      active site gorge. It is composed of five residues (Tyr 70, Asp 72, Tyr 121, Trp
      279 and Tyr 334; Torpedo numbering); associated with it are a number of surface
      loops, conferring a high degree of conformational flexibility on the area. The
      site is involved in the allosteric modulation of catalysis at the active centre
      and is the target of various anti-cholinesterases. It is also implicated in a
      number of non-classical functions, in particular, amyloid deposition, cell
      adhesion and neurite outgrowth. A number of peptide and protein ligands for the
      site have been identified. In this review, the structure and multiple functions
      of the peripheral anionic site are discussed, together with its potential as a
      target in rational drug design for the development of novel and improved
      inhibitors and of therapeutics for the treatment of neural cancers, nerve
      regeneration and neurodegenerative disorders such as Alzheimer's disease.

PMID- 16454739
TI  - Receptor-independent effects of endocannabinoids on ion channels.
AB  - Endogenous cannabinoids (endocannabinoids), produced from membrane-bound
      precursors via calcium and/or G-protein dependent processes, mimic the effects of
      cannabinoids by activating cannabinoid CB(1) and/or CB(2) receptors. Several
      reports however, also indicate that endocannabinoids can produce effects that are
      independent of cannabinoid receptors. Thus, in pharmacologically relevant
      concentrations, endocannabinoids have been demonstrated to modulate the
      functional properties of voltage-gated ion channels including Ca(2+) channels,
      Na(+) channels and various types of K(+) channels, and ligand-gated ion channels
      such as 5-HT(3), and nicotinic ACh receptors. In addition, the functional
      modulations by endocannabinoids of other ion-transporting membrane proteins such
      as transient potential receptor-class channels, gap junctions, and
      neurotransmitter transporters have also been reported. These findings indicate
      that additional molecular targets for endocannabinoids exist and that these
      targets may represent important sites for cannabinoids to alter either the
      excitability of the neurons or the response of the neuronal systems. This review
      focuses on the results of recent studies indicating that beyond their receptor
      mediated effects, endocannabinoids alter the function of ion channels directly.

PMID- 16454740
TI  - Promotion of remyelination by immunoglobulins: implications for the treatment of
      multiple sclerosis.
AB  - During the last decade immunomodulatory treatments have been shown to influence
      the natural course of multiple sclerosis (MS). However, demyelination in the
      central nervous system (CNS) still occurs and repair mechanisms are incomplete
      leading to neurological deficits. Currently, there is no therapy available to
      promote remyelination and thus enhance repair mechanisms. Both immunoglobulins
      directed against spinal cord homogenate and polyclonal immunoglobulins for
      intravenous use (IVIg) have been shown to support remyelination in the animal
      model of Theiler's virus encephalomyelitis (TMEV). Further studies have
      identified monoclonal antibodies that lead to remyelination in TMEV and a toxic
      demyelination model using lysolecithin. The shared characteristics of these
      monoclonal antibodies are an IgM isotype and the capacity to bind
      oligodendrocytes, independent of epitope specificity. Recently, two human
      monoclonal antibodies with remyelinating properties were described. Clinical
      trials with IVIg have so far failed to demonstrate clinical improvement in MS
      patients, but these studies only employed IgG preparations. However, recent
      experimental data both in vivo and in vitro underline the importance of IgM for
      remyelination. Thus future clinical trials are needed to evaluate the
      remyelination potential of IgM in human diseases. The design of monoclonal
      antibodies capable of promoting remyelination is a telling example for the design
      of new specific therapies derived from biological products like polyclonal
      immunoglobulins.

PMID- 16454741
TI  - Aspirin resistance: definitions, mechanisms, prevalence, and clinical
      significance.
AB  - Aspirin is the most commonly used therapeutic agent in prevention of vascular
      ischemic events. Aspirin exerts its antithrombotic effect primarily by
      interfering with the biosynthesis of thromboxane A2 (TXA2) and inhibition of TXA2
      -dependent platelet aggregation. A meta-analysis of secondary prevention trials
      indicated that aspirin reduced major cardiovascular or cerebral events by 25%.
      This led to the widespread use of aspirin for prevention of cardiovascular
      events. However, it appears that aspirin antiplatelet effect is not uniform in
      all patients and previous studies estimated that 8-45% of the population were
      aspirin resistant. Furthermore, (i) the optimal dosage of aspirin for complete
      inhibition of platelet aggregation by physiological agonists (i.e arachidonic
      acid) is subject to great interindividual variability, (ii) the tests to detect
      aspirin resistance in vitro are subject to debate and (iii) the mechanisms by
      which some patients are resistant to aspirin in vitro remain to be determined.
      Despite these unresolved questions, recent clinical studies provide the reliable
      evidence that aspirin resistance correlates with confirmed clinical
      unresponsiveness, highlighting the clinical interest of determining the aspirin
      inhibitory effects on patients' platelets. In conclusion, discovery of aspirin
      resistance in individuals might be important in order to devise better anti
      platelet strategies and improve our ability to prevent acute thrombotic
      complication.

PMID- 16454743
TI  - Evolution of resistance to cancer therapy.
AB  - Acquired drug resistance is a major limitation for successful treatment of
      cancer. Resistance emerges due to drug exclusion, drug metabolism and alteration
      of the drug target by mutation or overexpression. Depending on therapy, the type
      of cancer and its stage, one or several genetic or epigenetic alterations are
      necessary to confer resistance to treatment. The fundamental question is the
      following: if a genetically diverse population of replicating cancer cells is
      subjected to chemotherapy that has the potential to eradicate it, what is the
      probability of emergence of resistance? Here, we review a general mathematical
      framework based on multi-type branching processes designed to study the dynamics
      of escape of replicating organisms from selection pressures. We apply the general
      model to evolution of resistance of cancer cells and discuss examples for diverse
      mechanisms of resistance. Our theory shows how to estimate the probability of
      success for any treatment regimen.

PMID- 16454744
TI  - An update on overcoming MDR1-mediated multidrug resistance in cancer
      chemotherapy.
AB  - The intrinsic or acquired resistance to anticancer drugs remains one of the most
      significant factors impeding the progress of cancer chemotherapy. This phenomenon
      often involves simultaneous resistance to other anticancer drugs that differ in
      their chemical structure and mode of action and are not even used in
      chemotherapy. This phenotype has been called multidrug resistance (MDR). Although
      the cellular basis underlying MDR is not fully understood, several factors
      mediating therapy resistance in tumors have been proposed. One of the mechanisms
      leading to chemoresistance of tumor cells is the increased activity of
      transporter proteins. The best-characterized transporter protein is MDR1/P
      glycoprotein, and a number of clinical investigations have suggested that its
      intrinsic or acquired overexpression resulted in a poor clinical outcome of
      chemotherapy. Various types of compounds and techniques for the reversal of
      MDR1/P-glycoprotein-mediated MDR have been developed, and efforts have
      concentrated on the inhibition of function and suppression of expression. This
      review summarizes the current state of knowledge of MDR1/P-glycoprotein and the
      modulation of MDR by targeting MDR1/P-glycoprotein.

PMID- 16454745
TI  - Inhibition of multidrug resistance of cancer cells by natural diterpenes,
      triterpenes and carotenoids.
AB  - The multidrug resistance (MDR) proteins are member of the ATP-binding cassette
      superfamily and are present in a majority of human tumors. Their activity is a
      crucial factor leading to therapeutic failure. It is likely that compounds which
      inhibit the function of the MDR-efflux proteins such as MDR1 will improve the
      cytotoxic action of anticancer chemotherapy. Therefore, a search for MDR
      reversing compounds was conducted among three classes of plant derived compounds
      such as diterpenes, triterpenes and carotenoids in a hope to find inhibitors
      without adverse effects in these natural compounds. The inhibition of efflux
      activity was determined by measuring the accumulation of substrate analogues such
      as rhodamine in tumor cells in the presence of potential inhibitors. Thus we
      determined the effect of structurally unrelated diterpenes, triterpenes and
      carotenoids on reversal of multidrug resistance in MDR-1 gene-transfected L1210
      mouse lymphoma cells and MDR mediated multidrug resistance of human breast cancer
      cells MDA-MB-231 (HTB-26) and MCF-7. The majority of diterpenes, cycloartane
      triterpenes and carotenoids isolated from vegetables and medicinal plants were
      able to enhance rhodamine 123 accumulations of MDR-cells. Synergistic interaction
      was found between epirubicine and resistance modifier terpenoids in vitro. It is
      supposed that these MDR modulators bind into transmembrane domains and the action
      of ABC transporters is inhibited by induced conformational changes.

PMID- 16454746
TI  - Transport mechanism-based drug molecular design: novel camptothecin analogues to
      circumvent ABCG2-associated drug resistance of human tumor cells.
AB  - Acquired and intrinsic drug resistance in cancer is the major obstacle to long
      term, sustained patient response to chemotherapy. Irinotecan (CPT-11) is a widely
      used potent antitumor drug that inhibits mammalian DNA topoisomerase I (Topo I).
      However, overexpression of ABCG2 (BCRP/MXR/ABCP) reportedly confers cancer cells
      resistance to SN-38, the active form of CPT-11. To circumvent the ABCG2
      associated drug resistance, we have synthesized and characterized a total of
      fourteen new camptothecin (CPT) analogues with respect to both the inhibition of
      Topo I and the substrate specificity of ABCG2. While the lactone E ring is a
      prerequisite for anticancer activity, modifications of the A or B rings do not
      significantly affect Topo I inhibition activity. In this context, we have
      synthesized new CPT analogues with different substitutions at positions 10 or 11
      of the A ring. All of the tested CPT analogues strongly inhibited the Topo I
      activity in a cell-free system. Accordingly, we have examined ATP-dependent
      transport of those CPT analogues by using plasma membrane vesicles prepared from
      ABCG2-overexpressing cells. Based on the substrate specificity of ABCG2 thus
      evaluated, it is strongly suggested that CPT analogues with a hydroxyl group at
      position 10 or 11 of the A ring are good substrates for ABCG2 and therefore
      effectively extruded from cancer cells. Thus, hydrogen bond formation is
      considered to be involved in substrate recognition and/or transport processes of
      ABCG2. The present study provides a practical approach to discover new CPT-based
      drugs for the chemotherapy of drug-resistant human cancer.

PMID- 16454747
TI  - New treatment strategies for multiple myeloma by targeting BCL-2 and the
      mevalonate pathway.
AB  - Insight into the mechanisms of primary or acquired drug resistance of
      (hematological) malignancies is critical for the development of new treatment
      strategies. This review will focus on Bcl-2 and the mevalonate pathway as targets
      for reversal of drug resistance in multiple myeloma. The Bcl-2 protein is highly
      expressed in myeloma patients and in vitro studies have shown its role in the
      regulation of chemosensitivity, which makes Bcl-2 an attractive target for
      treatment. Statins are widely used for the treatment of hypercholesteremia.
      Several in vitro studies have shown that statins may also kill hematological
      malignant cells including myeloma cells. We found that lovastatin induced
      apoptosis in myeloma and lymphoma cells by inhibition of geranylgeranylation and
      subsequent down regulation of Mcl-1, probably the most important anti-apoptotic
      protein in myeloma. Phase 1 and 2 studies have been performed with Bcl-2
      antisense oligonucleotides and high dose simvastatin in combination with
      chemotherapy in heavily pre-treated myeloma patients. Encouraging results from
      these studies may provide the framework for the future application of new
      treatment strategies for myeloma.

PMID- 16454748
TI  - Transforming growth factor-beta: a molecular target for the future therapy of
      glioblastoma.
AB  - The median survival of patients with glioblastoma treated by surgery,
      radiotherapy and chemotherapy is in the range of 12 months. These limits in the
      efficacy of current treatment modalities call for the development of novel
      therapeutic approaches targeting the specific biological features of this type of
      cancer. Glioblastomas are a rich source of immunosuppressive molecules which may
      interfere with immune recognition and rejection as well as clinical strategies of
      active immunotherapy. The most prominent glioblastoma-associated
      immunosuppressant is the cytokine, transforming growth factor (TGF)-beta, a
      multifunctional cytokine which not only interferes with multiple steps of
      afferent and efferent immune responses, but also stimulates migration, invasion
      and angiogenesis. The complex regulation of TGF-beta bioavailability includes its
      synthesis as a proprotein, proteolytic processing by furin-like proteases,
      assembly in a latent complex, and finally liberation from latency by multiple
      effector mechanisms, a process collectively referred to as activation. Several in
      vitro paradigms and rodent glioma models have been used to demonstrate that the
      antagonism of TGF-beta holds promise for the treatment of glioblastoma, employing
      antisense strategies, inhibition of pro-TGF-beta processing, scavenging TGF-beta
      by decorin, or blocking TGF-beta activity by specific TGF-beta receptor (TGF
      betaR) I kinase antagonists. Moreover, the local application of TGF-beta(2)
      antisense oligonucleotides is currently evaluated in a randomized clinical trial
      for recurrent malignant glioma. In summary, we propose that TGF-beta-antagonistic
      treatment strategies are among the most promising of the current innovative
      approaches for glioblastoma, particularly in conjunction with novel approaches of
      cellular immunotherapy and vaccination.

PMID- 16454749
TI  - TRICOM vector based cancer vaccines.
AB  - For the immune system to mount an effective antitumor T-cell response, an
      adequate number of T-cells specific for the antigens expressed by the malignancy
      must be activated [1]. Since most antigens expressed by tumors are "self"
      antigens, tumor antigens often lack endogenous immunogenicity and thus do not
      sufficiently activate T-cells to levels that can mediate tumor eradication. In
      addition, virtually all solid tumor cells lack the costimulatory molecules
      necessary to activate tumor-specific T-cells. Approaches that stimulate immune
      responses to these tumor antigens have the potential to alter this poor
      responsiveness. This theory has promoted the use of active immunotherapy to
      generate immune responses against tumor-associated antigens (TAAs) for the
      treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as
      delivery vehicles for TAAs in combination with T-cell costimulatory molecules.
      Initial studies have demonstrated that the insertion of costimulatory molecule
      trangenes into viral vectors, along with a TAA transgene, greatly enhances the
      immune response to the antigen. Using this approach, a TRIad of COstimulatory
      Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell
      responses to TAAs to levels far greater than any one or two of the costimulatory
      molecules in combination. In this article, preclinical findings and recent
      clinical applications of TRICOM-based vaccines as a cancer immunotherapy are
      reviewed.

PMID- 16454750
TI  - Antibodies and their fragments as anti-cancer agents.
AB  - The recent developments in the field of recombinant DNA, protein engineering and
      cancer biology, have let us gain insight into many cancer-related mechanisms.
      Moreover, novel techniques have facilitated tools allowing unique distinction
      between malignantly transformed cells, to regular ones. This understanding has
      paved the way for the rational design of a new age of pharmaceuticals; monoclonal
      antibodies and their fragments. Antibodies can select antigens on both a specific
      and high affinity account, and further implementation of these qualities is used
      to target cancer cells by specifically identifying exogenous antigens of cancer
      cell populations. The structure of the antibody provides plasticity resonating
      from its functional sites. Upon binding to the Fc Receptor on effector cells, the
      crystallisable fragment (Fc) region elicits the onslaught of Antigen Dependent
      Cell-mediated Cytotoxicity (ADCC) and the plasma-native Complement Dependent
      Cytotoxicity (CDC) response and apoptosis. The progenitor form of the antibody
      can evolve in to a tailored therapeutic molecule with the help of recombinant DNA
      technology. Recombinant antibodies may be linked to potent toxins or radio
      labeled fragments, conferring a high killing capability. Other recombinant
      techniques such as ADEPT, conjugate the specificity of antibodies to a prodrug
      catalytic subunit thus creating a high local concentration of an activated
      chemotherapeutic. Antibodies can be used to recruit the adaptive immune response
      by binding the antibody fragment to a recombinant MHC molecule displaying a
      highly immunogenic peptide. Apart from their therapeutic capabilities antibodies
      are powerful detection tools as observed in the operating theater in a procedure
      known as Radio-immuno-guided Surgery (RIGS).

PMID- 16454751
TI  - Differentiation-inducing therapy for solid tumors.
AB  - Treating malignant tumor through the induction of cell differentiation has been
      an attractive concept, but clinical development of differentiation-inducing
      agents to treat malignant tumor, especially for solid tumors has been limited to
      date. Nerve growth factor, all trans retinoic acid, dimethyl sulfoxide, active
      form vitamin D(3), peroxisome proliferator-activated receptorgamma, 12-0
      tetradecanoylphorbol 13-acetate, hexamethylene-bis-acetamide, transforming growth
      factor-beta, butyric acid, cAMP, and vesnarinone are known to have a
      differentiation-inducing capability on solid tumors in vitro and/or in vivo.
      Moreover some of the differentiation-inducing agents have been used for treating
      patients with solid tumor, but the therapeutic effect of the differentiation
      inducing agents on solid tumor is not strong when compared with that of
      conventional chemotherapeutic agents. However, because most of the
      differentiation-inducing agents can potentiate the effect of conventional
      chemotherapy or radiation therapy, combination of differentiation-inducing
      therapy with conventional chemotherapy or radiation therapy might be used as a
      second- or third-line therapy in patients with advanced cancer. Furthermore,
      analysis of the molecular mechanisms of the tumor differentiation therapy might
      provide selective and targeted molecules for novel cancer therapy.

PMID- 16454753
TI  - The role of computers in pharmaceutical research.

PMID- 16454752
TI  - VEGF inhibitors in cancer therapy.
AB  - Vascular endothelial growth factor (VEGF)-mediated angiogenesis is thought to
      play a critical role in tumor growth and metastasis. Consequently, anti-VEGF
      therapies are being actively investigated as potential anti-cancer treatments,
      either as alternatives or adjuncts to conventional chemo or radiation therapy.
      Among the techniques used to block the VEGF pathway are: 1) neutralizing
      monoclonal antibodies against VEGF or its receptor, 2) small molecule tyrosine
      kinase inhibitors of VEGF receptors, 3) soluble VEGF receptors which act as decoy
      receptors for VEGF, and 4) ribozymes which specifically target VEGF mRNA. Recent
      evidence from phase III clinical trials led to the approval of bevacizumab, an
      anti-VEGF monoclonal antibody, by the FDA as first line therapy in metastatic
      colorectal carcinoma in combination with other chemotherapeutic agents. However,
      may challenges still remain, and the role of anti-VEGF therapy in the treatment
      of other solid tumors remains to be elucidated. The aim of this article is to
      review the progress of clinical investigations involving VEGF inhibitors in the
      treatment of different types of solid tumors.

PMID- 16454754
TI  - Diversity in medicinal chemistry space.
AB  - The chemical universe containing organic molecules within a reasonable molecular
      weight is vast and largely unexplored. Estimations of possible numbers of unique
      molecules range from 10(13) to 10(180). These numbers have to be compared with
      the few tens of millions of compounds currently known. Design of libraries that
      populate the medicinally relevant chemical subspace and tools that help to
      maximise the chance of identifying leads are necessary. This review describes
      various molecular representations that lead to the definition of chemical space,
      drug space or activity space. Strategies for compound selection in such spaces
      are discussed, as well as potential sources of diversity that could be used to
      explore the medicinal space in quest of new drugs.

PMID- 16454755
TI  - Recent developments in focused library design: targeting gene-families.
AB  - For many years, the most frequently optimized qualities of a screening library,
      or corporate compound collection, were size and diversity. Maximizing the number
      of diverse hits is the fundamental goal of such strategies. The ostensible
      justification that "bigger is better" is based on the large, estimated size of
      small-molecule space and the hypothesis that the notoriously low hit rates from
      high-throughput screening (HTS) could be overcome by brute force: i.e. by
      screening more compounds. Published, detailed studies about the success (or
      failure) of the brute-force strategy are rare, but it is well-known that it did
      not fulfill expectations. As a result, published reports in recent years have
      increasingly described methods for designing, selecting or synthesizing gene
      family-focused or -biased libraries. Moreover, many of the larger compound
      suppliers now sell such libraries, reflecting the growing interest in them from
      both the pharmaceutical and biotechnology markets. The trend towards gene family
      focused libraries marks the emergence of a different hypothesis about how to
      increase HTS hit rates and also reflects an increasingly pragmatic focus on the
      management of screening libraries. An important, underlying assumption in this
      trend is that a high-quality, general-purpose screening library of manageable
      size is neither realizable nor desirable. Whether a biasing strategy based on a
      specific gene family will do a better job of meeting both the scientific and
      business needs of the drug discovery enterprise still remains to be seen, but it
      is certainly an active area of current research. This review focuses on the "who,
      what, why, when, and how" of the design of gene family-focused libraries.
      Particular attention is given to reports that discuss not only the techniques
      used, but also any results obtained.

PMID- 16454756
TI  - Decision tree methods in pharmaceutical research.
AB  - Decision trees are among the most popular of the new statistical learning methods
      being used in the pharmaceutical industry for predicting quantitative structure
      activity relationships. This article reviews applications of decision trees in
      drug discovery research and extensions to the basic algorithm using hybrid or
      ensemble methods that improve prediction accuracy.

PMID- 16454757
TI  - Computational approaches to model ligand selectivity in drug design.
AB  - To be effective, a designed drug must discriminate successfully the
      macromolecular target from alternative structures present in the organism. The
      last few years have witnessed the emergence of different computational tools
      aimed to the understanding and modeling of this process at molecular level.
      Although still rudimentary, these methods are shaping a coherent approach to help
      in the design of molecules with high affinity and specificity, both in lead
      discovery and in lead optimization. It is the purpose of this review to
      illustrate the array of computational tools available to consider selectivity in
      the design process, to summarize the most relevant applications, and to sketch
      the challenges ahead.

PMID- 16454758
TI  - Acetylcholinesterase: molecular modeling with the whole toolkit.
AB  - Molecular modeling efforts aimed at probing the structure, function and
      inhibition of the acetylcholinesterase enzyme have abounded in the last decade,
      largely because of the system's importance to medical conditions such as
      myasthenia gravis, Alzheimer's disease and Parkinson's disease, and well as its
      famous toxicological susceptibility to nerve agents. The complexity inherent in
      such a system with multiple complementary binding sites, critical dynamic effects
      and intricate mechanisms for enzymatic function and covalent inhibition, has led
      to an impressively diverse selection of simulation techniques being applied to
      the system, including quantum chemical mechanistic studies, molecular docking
      prediction of noncovalent complexes and their associated binding free energies,
      molecular dynamics conformational analysis and transport kinetics prediction, and
      quantitative structure activity relationship modeling to tie salient details
      together into a coherent predictive tool. Effective drug and prophylaxis design
      strategies for a complex target like this requires some understanding and
      appreciation for all of the above methods, thus it makes an excellent case study
      for multi-tiered pharmaceutical modeling. This paper reviews a sample of the more
      important studies on acetylcholinesterase and helps to elucidate their
      interdependencies. Potential future directions are introduced based on the
      special methodological needs of the acetylcholinesterase system and on emerging
      trends in molecular modeling.

PMID- 16454760
TI  - Selective inhibitors of inducible nitric oxide synthase: potential agents for the
      treatment of inflammatory diseases?
AB  - Nitric Oxide (NO) is widely recognized as an important messenger and effector
      molecule in a variety of biological systems. There is strong evidence from animal
      models that elevated or lowered NO levels are associated with a variety of
      pathological states. In nature, NO is synthesised from the amino acid l-arginine
      by a small family of closely related oxygenase enzymes: the nitric oxide
      synthases (NOS). A number of studies in animals have associated excessive NO
      production by one of these enzymes--the inducible NOS isoform (iNOS or NOS-II)-
      with acute and chronic inflammation in model systems and have also demonstrated
      that administration of NOS inhibitors can produce beneficial effects.
      Regrettably, however, the relatively poor potency, selectivity and
      pharmacokinetic (ADME) profiles of the available inhibitors have so far precluded
      a convincing demonstration of their efficacy in the clinic. This review will
      describe the current state of knowledge of the structure and function of NOS and
      the various approaches that are being followed in the search for truly selective
      NOS inhibitors as therapeutic agents for inflammatory diseases.

PMID- 16454761
TI  - Atherosclerosis is an inflammatory disorder after all.
AB  - Inflammation has been increasingly recognized as an important player in the
      pathophysiology of numerous human disorders. Accumulating evidence has led to the
      conclusion that atherosclerosis is an inflammatory disease, although it was
      believed to be a disorder of high cholesterol levels in the bloodstream for over
      a century. Cholesterol does contribute to the pathogenesis of atherosclerosis,
      but through inflammatory mechanisms. Statins lower cholesterol levels and hence
      reduce inflammation in the vasculature and prevent heart disease. Statins may
      also exert anti-inflammatory effects through mechanisms independent of
      cholesterol lowering. Adhesion molecules, cytokines, oxidative stress, etc.
      appear to contribute to the inflammatory state of atherosclerosis and therapeutic
      approaches directed toward these markers or targets have the potential to be
      effective in reducing inflammation and treating atherosclerosis.

PMID- 16454762
TI  - Control of chronic inflammation with pathway selective estrogen receptor ligands.
AB  - The discovery of novel intervention points in the inflammatory pathway has been a
      focus of drug development in recent years. We have identified pathway selective
      ligands for the estrogen receptor (ER) that inhibit NF-kappaB mediated
      inflammatory gene expression causing a reduction of cytokines, chemokines,
      adhesion molecules and inflammatory enzymes. SAR development of a series of 4
      (Indazol-3-yl)-phenols has led to the identification of WAY-169916 an orally
      active non-steroidal ligand with the potential use in the treatment of
      inflammatory diseases without the classical proliferative effects associated with
      non-selective estrogens.

PMID- 16454763
TI  - New approaches to the treatment of inflammatory disorders small molecule
      inhibitors of p38 MAP kinase.
AB  - The therapy of chronic inflammatory diseases like rheumatoid arthritis (RA) and
      inflammatory bowel disease (IBD) has recently been enriched by the successful
      launch of the anti-cytokine biologicals Etanercept (tumor necrosis factor (TNF)
      receptor-p75 Fc fusion protein), Infliximab (chimeric anti-human TNF-alpha
      monoclonal antibody), Adalimumab (recombinant human anti-human TNF-alpha
      monoclonal antibody) and Anakinra (recombinant form of human interleukin 1beta
      (IL-1) receptor antagonist). The success of these novel treatments has
      impressively demonstrated the clinical benefit that can be gained from
      therapeutic intervention in cytokine signalling, highlighting the central role of
      proinflammatory cytokine systems like IL-1alpha and TNF-alpha to be validated
      targets. However, all of the anti-cytokine biologicals available to date are
      proteins, and therefore suffering to a varying degree from the general
      disadvantages associated with protein drugs. Therefore, small molecular, orally
      active anti-cytokine agents, which target specific pathways of proinflammatory
      cytokines, would offer an attractive alternative to anti-cytokine biologicals. A
      number of molecular targets have been identified for the development of such
      small molecular agents but p38 mitogen-activated protein (MAP) kinase occupies a
      central role in the regulation of IL-1beta and TNF-alpha signalling network at
      both the transcriptional and translational level. Since the mid-1990s, an immense
      number of inhibitors of p38 MAP kinase has been characterised in vitro, and to
      date several compounds have been advanced into clinical trials. This review will
      highlight the correlation between effective inhibition of p38 MAP kinase at the
      molecular target and cellular activity in functional assays of cytokine,
      particularly TNF-alpha and IL-1beta production. SAR will be discussed regarding
      activity at the enzyme target, but also with regard to properties required for
      efficient in vitro and in vivo activity.

PMID- 16454764
TI  - Neuropeptide mimetics and antagonists in the treatment of inflammatory disease:
      focus on VIP and PACAP.
AB  - Corticosteroids are the mainstay treatment for most severe inflammatory
      disorders. Due to the considerable toxicity associated with their long-term use,
      there is a great need for alternative treatments. Recently, two closely related
      neuropeptides with potent neuromodulatory activities, vasoactive intestinal
      peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have
      emerged as candidate molecules for the treatment of such pathologies. These
      peptides act primarily on three high affinity receptor subtypes expressed on
      multiple immune cell types, and orchestrate a cytokine response that is primarily
      anti-inflammatory. In this regard, systemic treatment with these peptides has
      been shown to greatly reduce the clinical symptoms and alter the pathogenic and
      cytokine profiles in animal models of rheumatoid arthritis, Crohn's disease,
      septic shock, and multiple sclerosis. Likewise, VIP and PACAP receptor knockout
      and overexpressing mice show altered immune responses in different models. We
      review here data demonstrating the potential effectiveness of these peptides in
      immune disorders, discuss receptor pharmacology and signaling pathways, describe
      the development of receptor specific agonists and antagonists, and discuss
      pharmaceutical considerations relevant to the specific delivery of analogs to the
      appropriate targets.

PMID- 16454765
TI  - Targeting the secretory pathway for anti-inflammatory drug development.
AB  - Inflammatory diseases are a complex group of disorders involving multiple levels
      of the immune system and as such present a daunting challenge to understand and
      treat. Contemporary drug development targets individual cytokines, chemokines,
      and receptors for which we have some knowledge of their function and regulation.
      One largely unexplored approach is to modify the inflammatory response via
      targets within the intracellular secretory pathway. This constitutive pathway is
      responsible for protein processing and trafficking quality control, and is
      comprised of the endoplasmic reticulum, the Golgi apparatus, and various post
      Golgi organelles such as lysosomes, endosomes, secretory granules, and the plasma
      membrane. Renewed interest in the secretory system has resulted from our
      expanding appreciation of the role of post-translational processing in protein
      function, the myriad of inflammatory and other diseases which arise from defects
      in the secretory system, and the outcome of drug treatments that utilize elements
      of this pathway to treat human disease. This review will examine the secretory
      pathway with particular attention to the phenotypes of diseases which result from
      disruption of its components, as well as the pharmacological agents that utilize
      the system to modulate aberrant cellular processes.

PMID- 16454767
TI  - Is the time overdue for an international reporting standard for convulsive
      paediatric status epilepticus?

PMID- 16454766
TI  - Characterization of Medicago truncatula (barrel medic) hydroperoxide lyase
      (CYP74C3), a water-soluble detergent-free cytochrome P450 monomer whose
      biological activity is defined by monomer-micelle association.
AB  - We describe the detailed biochemical characterization of CYP74C3 (cytochrome P450
      subfamily 74C3), a recombinant plant cytochrome P450 enzyme with HPL
      (hydroperoxide lyase) activity from Medicago truncatula (barrel medic). Steady
      state kinetic parameters, substrate and product specificities, RZ (Reinheitszahl
      or purity index), molar absorption coefficient, haem content, and new ligands for
      an HPL are reported. We show on the basis of gel filtration, sedimentation
      velocity (sedimentation coefficient distribution) and sedimentation equilibrium
      (molecular mass) analyses that CYP74C3 has low enzyme activity as a detergent
      free, water-soluble, monomer. The enzyme activity can be completely restored by
      re-activation with detergent micelles, but not detergent monomers. Corresponding
      changes in the spin state equilibrium, and probably co-ordination of the haem
      iron, are novel for cytochrome P450 enzymes and suggest that detergent micelles
      have a subtle effect on protein conformation, rather than substrate presentation,
      which is sufficient to improve substrate binding and catalytic-centre activity by
      an order of magnitude. The kcat/K(m) of up to 1.6x10(8) M(-1) x s(-1) is among
      the highest recorded, which is remarkable for an enzyme whose reaction mechanism
      involves the scission of a C-C bond. We carried out both kinetic and biophysical
      studies to demonstrate that this effect is a result of the formation of a complex
      between a protein monomer and a single detergent micelle. Association with a
      detergent micelle rather than oligomeric state represents a new mechanism of
      activation for membrane-associated cytochrome P450 enzymes. Highly concentrated
      and monodispersed samples of detergent-free CYP74C3 protein may be well suited
      for the purposes of crystallization and structural resolution of the first plant
      cytochrome P450 enzyme.

PMID- 16454768
TI  - Clinical trials in toxinology: more than a discussion between friends?

PMID- 16454769
TI  - Discharge planning and patient satisfaction in an emergency short-stay unit.
AB  - OBJECTIVES: To determine the adequacy of discharge planning from an emergency
      short-stay unit (ESSU), and patient knowledge of and satisfaction with the ESSU.
      METHODS: Prospective follow up of patients discharged from an ESSU using patient
      surveys and a computerized patient information system, with descriptive and
      comparative data analysis. RESULTS: Eighty-five per cent of respondents stated
      that they received adequate discharge instruction, and 89% that they benefited
      from their ESSU admission. However, 29% of patients made unscheduled visits to
      another medical practitioner post discharge and 9% were readmitted to hospital
      for the same problem with which they were discharged from the ESSU. Patient
      satisfaction with all aspects of care in the ESSU was high. CONCLUSIONS: Most
      patients discharged from an ESSU are provided with adequate discharge
      instruction, but a sizeable proportion require subsequent medical care for the
      same problem after discharge. Patient satisfaction with all aspects of care in an
      ESSU is high.

PMID- 16454770
TI  - Anaphylaxis to bull dog ant and jumper ant stings around Perth, Western
      Australia.
AB  - OBJECTIVE: To determine the main causative species, reaction characteristics and
      geographical locations of ant sting anaphylaxis around Perth, Western Australia
      (WA). METHODS: Structured interviews were performed on a cohort of 10 patients
      referred to our Anaphylaxis Clinic who were allergic to ant venom, followed by
      field trips to collect ant specimens. A descriptive analysis of clinical data was
      performed. RESULTS: Around Perth, Myrmecia gratiosa, a bull dog ant, was the only
      species of stinging ant found around the locations where reactions had occurred
      (eight patients). To the south-west of Perth, species implicated were another
      bull dog ant Myrmecia nigriscapa (one patient), and a jumper ant Myrmecia ludlowi
      (one patient). Twelve reactions were documented as mild (one), moderate (seven)
      and severe with hypotension (four). In three bull dog ant venom allergic
      patients, specific IgE was analysed, demonstrating substantial cross-reactivity
      with other bull dog ant species. Clinical patterns of reaction severity and
      response to repeated stings were consistent with known features of insect sting
      allergy. CONCLUSIONS: A single species of bull dog ant, M. gratiosa, appears to
      be responsible for ant sting anaphylaxis around Perth. Further investigation is
      required for other regions of WA. The provision of effective immunotherapies for
      people allergic to native Australian ants might be simplified by the dominance of
      a limited number of ant species and IgE binding cross-reactivity between venoms,
      as was evident in this study.

PMID- 16454771
TI  - Review of morbidity and mortality associated with falls from heights among
      patients presenting to a major trauma centre.
AB  - OBJECTIVE: To compare differences in demographics and injuries of patients
      presenting after falls from heights at home and at work. METHOD: A retrospective
      case series review of patients treated by the Royal Adelaide Hospital (RAH)
      Trauma Service following a fall from a ladder, scaffold, building, or tree
      between July 2000 and December 2003. RESULTS: Two hundred and eighty-two patients
      fulfilled study criteria. The 162 (57.4%, 95% confidence interval [CI] 48.9-60.5)
      injured at home were significantly (P < 0.001) older (mean age 53.9 years, 95% CI
      51.3-56.7) than those injured at work (mean age 41.2 years, 95% CI 38.6-43.8).
      Injury severity score (ISS) was similar in the two groups. Those injured at home
      were more likely to be admitted to hospital and have significantly longer
      hospital stays (P = 0.003). Thirteen deaths were recorded, eight (61.5%) from
      home, all over 49 years old. Ladders were implicated in seven (53.8%, 95% CI 26.7
      80.9) of the deaths. A 67% (95% CI 55.4-79.0) increase in the number of
      presentations following falls at home over the study period was significantly
      greater than the 12.2% (95% CI 10.7-13.7) increase in total trauma presentations
      during this time (P = 0.0007). CONCLUSIONS: Injuries resulting from falls at home
      are increasing. This group tends to be elderly and at risk of significant injury
      and prolonged hospital stays. Causes are multifactorial and might be related to
      increased popularity of home renovations. Ladders are implicated in many of these
      accidents. As emergency physicians we should target this population to educate
      them in safe ladder use.

PMID- 16454772
TI  - Timed Up and Go test is not useful as a discharge risk screening tool.
AB  - OBJECTIVE: To determine whether the 'Timed Up and Go' (TUG) test is a useful test
      for predicting re-attendance at an ED, emergency hospital admission or death
      within 90 days in elderly patients discharged from the ED. METHODS: This was a
      prospective blinded cohort study at a tertiary referral ED. Patients completed a
      TUG test during their Allied Health assessment prior to discharge from the
      department. After 90 days, patient ED attendances, emergency admissions to
      hospital or deaths were recorded and confirmed by phone. Data were analysed using
      logistic regression and reported as odds ratios (OR) or log-transformation and
      Pearson analysis. RESULTS: One hundred patients were enrolled: 78 (78%, 95%
      confidence interval [CI] 70-86%) patients remained event free, 22 (22%, 95% CI 14
      30%) patients re-attended an ED and 15 (15%, 95% CI 8-22%) were admitted to
      hospital as an emergency admission. There was no significant difference between
      TUG test times and whether patients re-attended an ED (OR 1.0 [0.93-1.06] P =
      0.9) or were admitted to hospital (OR 0.99 [0.91-1.07] P = 0.74). There was no
      significant correlation between a patient's TUG test time and the number of days
      to ED re-attendance (Pearson correlation coefficient 0.38 [-0.04 to 0.69] P =
      0.08) or admission (Pearson correlation coefficient 0.32 [-0.23 to 0.71] P =
      0.25). CONCLUSION: This study did not detect any predictive value of the TUG test
      for ED re-attendance or hospital admission within 90 days of discharge among aged
      ED patients.

PMID- 16454773
TI  - Ketamine for rapid sequence induction in patients with head injury in the
      emergency department.
AB  - OBJECTIVE: To examine the evidence regarding the use of ketamine for induction of
      anaesthesia in patients with head injury in the ED. METHOD: A literature review
      using the key words ketamine, head injury and intracranial pressure. RESULTS:
      Advice from early literature guiding against the use of ketamine in head injury
      has been met with widespread acceptance, as reflected by current practice. That
      evidence is conflicting and inconclusive in regards to the safety of using
      ketamine in head injury. A review of the literature to date suggests that
      ketamine could be a safe and useful addition to our available treatment
      modalities. The key to this argument rests on specific pharmacological properties
      of ketamine, and their effects on the cerebral haemodynamics and cellular
      physiology of brain tissue that has been exposed to traumatic injury. CONCLUSION:
      In the modern acute management of head-injured patients, ketamine might be a
      suitable agent for induction of anaesthesia, particularly in those patients with
      potential cardiovascular instability.

PMID- 16454774
TI  - When benzodiazepines fail: how effective is second line therapy for status
      epilepticus in children?
AB  - OBJECTIVES: To define the characteristics and management of children presenting
      to the ED of a major tertiary paediatric hospital with convulsive status
      epilepticus (CSE). To determine the timing and efficacy of therapeutic
      interventions in this group and to identify factors that influence the
      effectiveness of treatment. METHOD: A retrospective audit of all children who
      presented to an ED of a tertiary paediatric hospital in CSE over a 3 year period.
      RESULTS: Thirty-seven cases were identified. Prehospital treatment had been
      administered in 51%. Uncomplicated seizure control was achieved in 30% with the
      combination of first and second line therapy. Rapid sequence induction (RSI) of
      anaesthesia was required in 70% for the control of ongoing seizure activity (21
      cases) or to support severe respiratory depression (five cases). This requirement
      for RSI was increased to 85% in those with seizure duration in excess of 30 min
      and 89% of those who received prehospital treatment. Of those who required RSI,
      35% were treated for periods in excess of 60 min before this intervention was
      performed. CONCLUSIONS: Standard second line anticonvulsant treatment was
      relatively ineffective in terminating seizures in children who presented in CSE
      not responsive to benzodiazepines. Failure to respond to prehospital treatment
      and prolonged seizure duration at presentation both predict poor therapeutic
      response. Third line treatment with RSI of anaesthesia is often delayed while
      waiting for second line treatment to work.

PMID- 16454775
TI  - Paediatric prehospital analgesia in Auckland.
AB  - OBJECTIVES: The objectives of the present study were: To determine whether the
      age of a child influences the likelihood of their receiving prehospital analgesia
      from the Auckland ambulance service. To investigate the effect of age on
      ambulance officers' decision-making and use of analgesia. METHODS: A prospective
      study of children arriving by ambulance at Starship Children's Emergency
      Department Auckland, with a diagnosis of limb fracture or burn, was undertaken
      over 2 months in 2002. A concurrent questionnaire survey investigated ambulance
      officers' use of analgesia in children. RESULTS: No child aged less than 5 years
      (n = 10) compared with 51% between 5 and 15 years of age (n = 35) received
      prehospital analgesia (P = 0.003). On arrival in hospital 70% aged less than 5
      years compared with 54% older than 5 years required i.v. opiate analgesia.
      Ambulance officers did not perceive that a child's age would significantly alter
      their decision to use analgesia. CONCLUSIONS: In children, younger age is a
      significant risk factor for receiving inadequate prehospital analgesia. Ambulance
      officers' concern about the pain of injection is the major identified factor for
      the relative underuse of morphine observed in younger children.

PMID- 16454776
TI  - Paediatric lap-belt injury: a 7 year experience.
AB  - OBJECTIVE: To highlight the injuries that result from lap-belt use and make
      recommendations for prevention, the recent experience of a regional paediatric
      trauma centre was reviewed. METHODS: Retrospective review of admissions to
      Starship Children's Hospital from 1996 to 2003, with significant injury following
      involvement in a motor vehicle crash, while wearing a lap-belt. Patients were
      identified from two prospectively collected databases and discharge coding data.
      RESULTS: In total, 19 patients were identified over the 7 year period. The
      morbidity sustained includes 15 patients with hollow viscus injury, 13
      laparotomies, 7 spinal fractures, 2 paraplegia and 1 fatality. A total of 11
      patients required laparotomy with a median delay of 24 h. Of patients in the
      present series, 58% were aged less than 8 years and thus were inappropriately
      restrained. CONCLUSIONS: Lap-belt use can result in a range of life-threatening
      injuries or permanent disability in the paediatric population. The incidence of
      serious lap-belt injury does not appear to be decreasing. Morbidity and mortality
      could be reduced by the use of three-point restraints, age appropriate restraints
      and booster seats.

PMID- 16454777
TI  - The case for venous rather than arterial blood gases in diabetic ketoacidosis.
AB  - OBJECTIVES: For patients with diabetic ketoacidosis (DKA), arterial blood gas
      (BG) sampling for measurement of pH and bicarbonate has been considered an
      essential part of initial evaluation and monitoring of progress. There is growing
      evidence that venous values can be clinically acceptable alternatives to arterial
      measurements. This article summarizes the recent evidence regarding the validity
      of venous BG sampling in DKA. METHODS: Medline search for the years 1995 to
      present, hand search of reference lists, search of on-line evidence-based
      medicine sites. RESULTS: In patients with DKA the weighted average difference
      between arterial and venous pH was 0.02 pH units (95% limits of agreement -0.009
      to +0.021 pH units) and between arterial and venous bicarbonate was -1.88 mEq/L.
      CONCLUSIONS: There is reasonable evidence that venous and arterial pH have
      sufficient agreement as to be clinically interchangeable in patients with DKA who
      are haemodynamically stable and without respiratory failure. There is some
      evidence that venous and arterial bicarbonate also agree closely in DKA but this
      requires confirmation.

PMID- 16454778
TI  - Use of emergency departments by Aboriginal and Torres Strait Islander people.
AB  - OBJECTIVE: To review published Australian literature about ED care of Aboriginal
      and Torres Strait Islander peoples. METHOD: Six databases were searched
      electronically for articles about ED use by Indigenous people in Australia. This
      strategy was complemented by manual searches of two websites, Emergency Medicine
      (1994-2004) and three bibliographies. RESULTS: Aboriginal and Torres Strait
      Islander peoples attend EDs about twice as often as other Australians. The
      waiting times of Indigenous patients are similar to, or slightly shorter than,
      those of non-Indigenous patients. However, more Indigenous than other patients
      choose to walk out before being seen, indicating possibly greater Indigenous
      dissatisfaction with ED care. CONCLUSIONS: Further conclusions of the present
      literature review were limited by contradictory results in the few studies of
      reasonable quality and by general concerns about data quality, especially the
      poor (but slowly improving) identification of Indigenous people in routine ED
      data sets. Closer collaboration between ED staff and Indigenous hospital liaison
      staff, combined with regular monitoring of routinely-collected ED data, have the
      potential to improve Indigenous ED care and so contribute to improvements in
      Indigenous health.

PMID- 16454779
TI  - Baclofen overdose: defining the spectrum of toxicity.
AB  - OBJECTIVES: To describe the spectrum of toxicity of baclofen in overdose, and
      investigate dose-related clinical effects. METHODS: Consecutive baclofen
      overdoses were identified from a prospective database of all poisoning admissions
      presenting to a regional toxicology service. Ingestion was corroborated on more
      than one occasion and from multiple sources. Demographic, clinical and outcome
      variables were extracted for each presentation for a retrospective review, and
      the data sets were divided into high dose (> or = 200 mg) and low dose (< 200 mg)
      groups for comparison of clinical effects. RESULTS: There were 23 presentations,
      of which eight patients ingested baclofen alone. Seizures were reported in four
      cases, a decreased level of consciousness (GCS < 9) occurred in eight patients
      and delirium was recorded in eight patients. Five patients had miosis and seven
      patients had dilated pupils, 13 patients had absent or depressed reflexes. The
      only arrhythmias were sinus bradycardia in six patients and sinus tachycardia in
      five. Hypertension occurred in 13 patients and hypotension in one. The reported
      total ingested dose of baclofen was known in 19 patients (Mean 630 mg, SD 730 mg;
      80-2500 mg). A higher ICU admission rate, rate of mechanical ventilation and
      prolonged length of stay occurred in those ingesting 200 mg or more. Coma,
      delirium and seizures occurred only with doses of 200 mg or more, and
      hypertension was more common with higher doses. CONCLUSIONS: Baclofen overdose
      causes mainly neurological effects and excepting hypertension cardiovascular
      effects were uncommon. Doses greater than 200 mg were predictive of patients
      developing delirium, coma and seizures, requiring long hospital admissions and
      ICU admission.

PMID- 16454780
TI  - Brainstem anaesthesia after retrobulbar block: a rare cause of coma presenting to
      the emergency department.
AB  - Local anaesthesia, in particular retrobulbar block, is commonly used to perform
      cataract surgery. Known complications of retrobulbar block include cranial nerve
      palsies, seizures and cardiorespiratory arrest. We report a case of brainstem
      anaesthesia causing apnoea and loss of consciousness in a man who received
      retrobulbar block. The likely mechanism is inadvertent dural puncture of the
      optic nerve sheath and local anaesthetic injection into the cerebrospinal fluid
      space. As in this case, the literature reports a short-lived period of
      anaesthesia with usually no long-term sequelae. Although rare, it is a life
      threatening complication if the patient is not appropriately resuscitated. This
      case highlights the need for trained personnel, with suitable monitoring and
      adequate resuscitation facilities in order to perform this technique.

PMID- 16454781
TI  - Responding to the Boxing Day tsunami disaster in Aceh, Indonesia: Western and
      South Australian contributions.
AB  - OBJECTIVE: To describe the Western and South Australian response to the Boxing
      Day tsunami disaster in Aceh, Indonesia. METHOD: Reports from three of the
      responders. RESULTS: Comment has been made on organising a response, the first
      team to Banda Aceh, the second team to Banda Aceh, and lessons learned.
      CONCLUSIONS: These experiences have identified areas in which we could be better
      prepared for the next international disaster response.

PMID- 16454782
TI  - Early post-tsunami disaster medical assistance to Banda Aceh: a personal account.
AB  - The south Asian tsunami on 26 December, 2004, saw Australia deploy civilian teams
      to an international disaster in large numbers for the first time. The logistics
      of supporting such teams in both a self sustainability capacity and medical
      equipment had not previously been planned for or tested. For the first Australian
      team deployed to Banda Aceh, which arrived on the fourth day after the tsunami,
      equipment sourced from the New South Wales Fire Brigades Urban Search and Rescue
      (US&R) cache supplied all food, water, tents, generators and sleeping equipment.
      The medical equipment was largely sourced from the CareFlight US&R medical cache.
      There were significant deficits in surgical equipment as the medical cache had
      not been designed to provide a stand alone surgical capability. This resulted in
      the need for substantial improvisation by the surgical teams during the
      deployment. Despite this, the team performed nearly 140 major procedures in
      austere circumstances and significantly contributed to the early international
      response to this major humanitarian disaster.

PMID- 16454786
TI  - Cricoid pressure for emergency airway management.

PMID- 16454788
TI  - An ex vivo evaluation of a new root canal irrigation technique with intracanal
      aspiration.
AB  - AIM: To evaluate the effectiveness of a new root canal irrigation technique with
      intracanal aspiration in removing the smear layer and to assess irrigant
      extrusion ex vivo. METHODOLOGY: Thirty-five instrumented canals of extracted
      human canine teeth that had been resected apically by removing 3 mm of the root
      tip were divided into one control and four experimental groups of seven teeth
      each. The roots were fixed in a plastic case and surrounded with normal saline
      agar coloured with 1% acid red. No irrigation was performed in the control teeth.
      Each root canal in the experimental groups was irrigated with 9 mL of 14%
      ethylenediaminetetraacetic acid for 3 min, and then with 6 mL of 6% sodium
      hypochlorite (NaOCl) for 2 min. In the intracanal aspiration technique, the
      irrigant was delivered from the tip of an injection needle placed 12 mm from the
      apical root-end and an aspiration needle that was connected to a Root ZX apex
      locator placed 2 and 3 mm short of the apical root-end in groups 1 and 2,
      respectively. In the conventional method, the tip of an injection needle used for
      delivery of the irrigant and as an active electrode was placed 2 and 3 mm short
      of the apical root-end in groups 3 and 4, respectively, the tip of the aspiration
      needle was placed 12 mm from the apical root-end in these groups. The readings of
      the Root ZX during irrigation were recorded. The cleanliness of the canal was
      evaluated by scoring smear layer from scanning electron microscopy (SEM) images
      of the canal. Extrusion of NaOCl was detected by measuring the discoloured area
      of the agar around the apical root-end. The data obtained were statistically
      analysed by one-way anova, the Kruskal-Wallis test and Friedman's test. RESULTS:
      In the SEM study, the canals in groups 1-3 were significantly cleaner than those
      in the control and group 4 (P < 0.05). The mean Root ZX readings in groups 1-3
      were approximately "0.5". The discoloured area in group 3 was significantly
      larger than the other groups (P < 0.05). CONCLUSIONS: Irrigation using the
      intracanal aspiration technique allowed more effective removal of the smear layer
      than that performed by the conventional method in an apically resected canine
      tooth. The intracanal aspiration technique produced limited extrusion of the
      irrigant beyond the apical foramen.

PMID- 16454789
TI  - Longitudinal study of periapical and endodontic status in a Danish population.
AB  - AIM: To describe and discuss changes in periapical and endodontic status in a
      general Danish population. METHODOLOGY: In 1997, 616 randomly selected
      individuals had a full-mouth radiographic survey taken. In 2003, 77% of the
      participants attended for a new full-mouth radiographic examination. Information
      on endodontic treatment and periapical status was obtained. The periapical index
      (PAI) was used to assess apical periodontitis (AP). RESULTS: More participants
      had root filling(s) and AP in 2003 than in 1997. More teeth had AP and/or root
      fillings in 2003. Fewer of the root-filled teeth (RFT) had AP in 2003. Less than
      3% of the teeth without root fillings (NRFT) that in 1997 had no AP, developed AP
      and/or received a root filling. Of the NRFT which in 1997 had AP, more than 35%
      still had AP and no root filling in 2003. Approximately, 30% of the NRFT with AP
      in 1997 received a root filling. Of the teeth that received a root filling, 40%
      had healed, whereas 60% had not. Approximately, 25% of the NRFT that in 1997 had
      AP had been extracted. In 1997 there were 618 RFT, 314 of the RFT had no AP in
      1997. Almost 20% of the RFT that in 1997 were periapically sound, developed AP.
      Of the 304 RFT with AP in 1997, approximately 30% had healed, in 60% AP
      persisted, and 10% were extracted. CONCLUSIONS: The present study indicates that
      caution must be exercised when statements on the outcome of root canal treatment
      are made based on the cross-sectional studies.

PMID- 16454790
TI  - A simple mounting model for consistent determination of the accuracy and
      repeatability of apex locators.
AB  - AIM: To develop a precise and simple mounting model (MM) for evaluating apex
      locators and to compare the repeatability of the MM with a conventional visual
      method (VM). METHODOLOGY: Electronic working length determination was performed
      in 32 maxillary central incisors using two methods: (i) the MM method and (ii) a
      conventional VM. The MM utilizes a micrometer to determine the distance travelled
      by the measuring file during working length determination. In the VM, the length
      of the measuring file (representing the working length) is determined visually
      using a caliper and a microscope at 6x magnification. Each measurement was
      repeated once. The repeatability of each method was evaluated by calculating the
      coefficient of repeatability. RESULTS: The coefficient of repeatability, which
      includes 95% of the differences between repeated measurements, was 0.04 mm for MM
      compared with 0.9 mm for VM. The measurement error of MM was significantly lower
      than VM (0.02 and 0.4 mm respectively). There was a statistically significant
      difference between the means of absolute difference in repeated measurements: MM
      0.01 mm (95% confidence interval (CI): 0.01; 0.02 mm) compared with VM 0.4 mm
      (95% CI: 0.3; 0.5 mm). CONCLUSION: The new MM had superior repeatability in
      comparison with the conventional method where visual interpretation is a source
      of inaccurate measurement.

PMID- 16454792
TI  - Influence of phase transformation on the torsional and bending properties of
      nickel-titanium rotary endodontic instruments.
AB  - AIM: To investigate the relationship between the functional properties and the
      phase transformation of nickel-titanium endodontic instruments. METHODOLOGY: Five
      types of rotary nickel-titanium endodontic instruments with a 0.30 mm diameter
      tip (EndoWave, HERO 642, K3, ProFile.06, and ProTaper) were selected to
      investigate torsional and bending properties, and phase transformation behaviour.
      A torsional test was performed according to ISO publication 3630-1, and maximum
      torque and angular deflection at fracture were measured. Bending load of the
      instruments was measured in a cantilever-bending test at 37 degrees C with the
      maximum deflection of 4.0 mm. A stainless steel K-file was used for reference.
      Phase transformation behaviour was measured by differential scanning calorimetry
      (DSC). From the DSC curve, transformation temperatures were calculated. Data were
      analysed by anova and the Tukey-Kramer's test. RESULTS: The maximum torsional
      torque values of HERO, K3 and ProTaper were significantly higher (P < 0.05) than
      those of EndoWave, ProFile and K-file. The K-files had the lowest torque value.
      Angular deflection at fracture was significantly higher (P < 0.05) for K-files
      than that for any nickel-titanium instrument. The bending load values of HERO and
      K3 were significantly higher (P < 0.05) than those of EndoWave, ProFile, ProTaper
      and K-file. The K-files had the lowest load value, although residual deflection
      remained. The transformation temperatures of HERO and K3 were significantly lower
      (P < 0.05) than those of EndoWave, ProFile and ProTaper. CONCLUSIONS: The
      functional properties of nickel-titanium endodontic instruments, especially their
      flexible bending load level, were closely related to the transformation behaviour
      of the alloys.

PMID- 16454791
TI  - Assessment of different gutta-percha brands during the filling of simulated
      lateral canals.
AB  - AIM: To compare the ability of five different commercially available gutta-percha
      points to fill simulated lateral canals when subjected to warm vertical
      compaction. METHODOLOGY: Fifty clear plastic teeth with a lateral canal in each
      third of the root were used. All teeth were filled using warm vertical
      compaction. Backfilling was completed with a sealer and the same gutta-percha
      point used during the apical condensation. After this, they were horizontally
      sectioned using a diamond disc adapted to a low-speed saw. The resulting sections
      were embedded in epoxy resin. The extent of gutta-percha and sealer filling were
      measured in each lateral canal using an IMAGE-PRO 4.0 software system. The voids
      in each canal were measured using the same system. Data were ranked and analysed
      using the Kruskal-Wallis statistical test. RESULTS: The mean percentage of the
      three lateral canals filled with gutta-percha and sealer were respectively: Konne
      (68.23% and 24.50%), Analytic (67.90% and 25.28%), Obtura (63.80% and 29.60%),
      Tanari (49.42% and 45.86%) and Dentsply (44.60% and 47.05%). There was
      significantly (P < 0.05) more gutta-percha in the lateral canal filled with
      Analytic, Obtura and Konne points than with Tanari and Dentsply points.
      CONCLUSIONS: The brand of gutta-percha cone had an influence on the length of
      filling within lateral canals. This may be a reflection of the chemical
      formulation of the gutta-percha points.

PMID- 16454793
TI  - Evaluation of the accuracy of three electronic apex locators using glass tubules.
AB  - AIM: To evaluate the accuracy of three different electronic apex locators (EALs)
      using glass tubules. METHODOLOGY: Forty-eight glass tubules with different
      diameters and an agar model were used to mimic root canals. A size 15 stainless
      steel K-file was used as the measuring electrode. The Root ZX, Propex and Neosono
      Ultima EZ were used to measure the tubule length with tubules dry, or filled with
      0.9% NaCl, 3% H(2)O(2), 2.5% NaOCl or 17% EDTA. The distance between the real
      length (RL) and measured length (ML) of the tubules was recorded. The range of RL
      +/- 0.5 mm and RL +/- 1 mm was used to evaluate the accuracy of the EALs. Results
      were subject to correlation analysis and Friedman's test. RESULTS: In dry
      tubules, the accuracy of Root ZX was 75-91.7% for RL +/- 0.5 mm and 100% for RL
      +/- 1 mm, whilst the measurements of the other two EALs were all within the RL +/
      0.5 mm. No influence from the increase in tubule diameter on the accuracy of all
      three EALs was observed in dry tubules. In tubules filled with electrolyte, the
      accuracy of the Root ZX decreased as tubule diameter increased (R(d) > 0, P <
      0.05). The RL-ML distance recorded by Propex was inversely related to the tubule
      diameter (R(d) < 0, P < 0.05). The accuracy of Propex was 75-100% for RL +/- 0.5
      mm and 100% for RL +/- 0.5 mm when the tubule diameter was not more than 0.80 mm,
      but decreased in tubules with diameter over 0.80 mm and filled with 2.5% NaOCl or
      17% EDTA. Nearly, all the measurements (except for six tubules) using Neosono
      Ultima EZ were within 1 mm shorter than RL despite the contents in tubules and
      the increase of tubule diameter. CONCLUSIONS: The accuracy of the Root ZX
      decreased as the tubule diameter increased when tubules were filled with
      electrolytes. The electrolytes in the tubules decreased the accuracy of Propex
      when the tubule diameter was large. The electrolytes in tubules and tubule
      diameter had no influence on the accuracy of Neosono Ultima EZ. The Propex and
      Neosono Ultima EZ were more accurate than the Root ZX under various conditions in
      this laboratory study.

PMID- 16454794
TI  - Reinforcement effect of polyethylene fibre in root-filled teeth: comparison of
      two restoration techniques.
AB  - AIM: To compare in vitro two different fibre placement techniques on
      reinforcement of root-filled molar teeth with mesio-occluso-distal (MOD)
      cavities. METHODOLOGY: Fifty sound extracted human mandibular molars were used (n
      = 10). Group 1 served as control. From group 2-5, endodontic access and standard
      MOD cavities were prepared. Following root canal treatment, group 2 was kept
      unrestored. In groups 3 and 4, the teeth were restored with composite resin (AP
      X; Kuraray, Japan). A groove was prepared on occlusal surface of the finished
      restorations in group 4 from buccal to lingual direction. Polyethylene woven
      fibre (Ribbond; Seattle, WA, USA) was inserted in the groove in combination with
      flowable resin that was cured for 20 s and covered with composite resin. Cavity
      surfaces were covered with flowable resin in group 5, and polyethylene fibre was
      placed into the bed of resin in a buccal to lingual direction before the
      composite restoration was placed. All specimens were stored in 100% humidity at
      37 degrees C for 24 h. Compressive loading of the teeth was performed by a
      universal testing machine at a crosshead speed of 0.5 mm min(-1) until failure.
      The data were recorded in Newton and submitted to anova and Tukey post hoc test.
      RESULTS: The mean load necessary to fracture the samples in each group was: G1:
      1671.57 +/- 131.54(a); G2: 375.21 +/- 34.30(b); G3: 749.47 +/- 124.54(c); G4:
      1224.36 +/- 132.17(d); G5: 926.88 +/- 118.28(e). Different superscript letters
      demonstrate significant difference between groups. CONCLUSIONS: Polyethylene
      fibre use over or under MOD composite restorations significantly increased
      fracture strength. However, when the fibre was placed on the occlusal surface of
      the restoration in buccal to lingual direction, significantly higher fracture
      resistance was observed.

PMID- 16454795
TI  - The effect of pre-soaking and time in the ultrasonic cleaner on the cleanliness
      of sterilized endodontic files.
AB  - AIMS: To assess whether pre-soaking files in an enzymatic cleaner prior to
      ultrasonic cleaning had any effect on cleanliness and also to assess the effect
      of the time that endodontic files spend in an ultrasonic bath prior to
      sterilization on their overall cleanliness. METHODOLOGY: Twenty root canals in a
      total of ten patients were cleaned and shaped using conventional techniques.
      Following use, some of the files were pre-soaked and then ultrasonically cleaned
      for either 5, 10, 30 or 60 min. Other files had no pre-soaking and were then
      ultrasonically cleaned. There were two control groups, one where the files were
      pre-soaked and not ultrasonically cleaned and the other where the files were
      neither pre-soaked nor ultrasonically cleaned. All files were then subjected to a
      standard packing and autoclaving process. Following autoclaving, the files were
      examined using a light microscope at a magnification of 40x. The cutting section
      of each file was divided into two parts, the tip and the shaft, for visualization
      under the microscope. Any debris or cement on the files was scored using a
      modification of the scale used by Smith et al. (Journal of Hospital Infection,
      51, 2002, 233). The data were analysed using one-way analysis of variance.
      RESULTS: Pre-soaking had no significant effect on the cleanliness of the files (P
      = 0.18 at the tip, P = 0.93 at the shaft). Ultrasonic cleaning had a significant
      effect on the cleanliness of the files (P < 0.00) but there was not a linear
      relationship between cleanliness and the ultrasonic cleaning time. There was
      little benefit in extending the ultrasonic cleaning time beyond 5 min. Calcium
      hydroxide deposits on two files were resistant to ultrasonic cleaning.
      CONCLUSIONS: There is no benefit in pre-soaking endodontic files prior to
      ultrasonic cleaning. The optimum time for ultrasonic cleaning was between 5 and
      10 min. Further ultrasonic exposure, up to 60 min, did not improve cleanliness.
      Although a majority of files were free from debris following ultrasonic cleaning,
      a substantial minority still retained debris. This supports the case for
      endodontic files being single-use only.

PMID- 16454796
TI  - Effectiveness of hand and rotary instrumentation for removing a new synthetic
      polymer-based root canal obturation material (Epiphany) during retreatment.
AB  - AIM: To evaluate the effectiveness of hand and rotary instrumentation for removal
      of vertically compacted Epiphany and gutta-percha during retreatment.
      METHODOLOGY: Sixty extracted single-rooted maxillary central incisors were
      enlarged to size 40 using FlexMaster instruments. The teeth were randomly divided
      into four groups of 15 specimens each. The canals of two groups were obturated
      using vertically compacted Epiphany. The others were filled with vertically
      compacted gutta-percha and AH Plus sealer. One Epiphany group and one gutta
      percha group was reinstrumented with Gates Glidden burs and Hedstrom files. In
      the other two groups, obturation material was removed using Gates Glidden burs
      and RaCe rotary instruments. After clearing the roots, the area of remaining
      obturation material on the root canal wall was measured using a computer image
      analysis program. Statistical analysis was performed using Repeated Measures
      Analysis of Variance and anova. RESULTS: Retreatment of specimens obturated with
      gutta-percha showed significantly more remaining obturation material than
      specimens filled with Epiphany (P < 0.05). No difference was found between the
      removal with Hedstrom files and with RaCe instruments (P > 0.05). Regarding the
      mean time of retreatment and time required for reaching the working length,
      Hedstrom files were significantly faster than RaCe instruments (P < 0.05). The
      times did not depend on the kind of obturation material (P > 0.05). CONCLUSIONS:
      Vertically compacted Epiphany in combination with Epiphany Root Canal Sealant was
      removed more effectively than gutta-percha and AH Plus sealer. Hedstrom files
      were more rapid than RaCe rotary instruments.

PMID- 16454797
TI  - Palatal mucosa necrosis because of accidental sodium hypochlorite injection
      instead of anaesthetic solution.
AB  - AIM: A case is reported in which sodium hypochlorite (NaOCl) was inadvertently
      injected into the palatal mucosa instead of local anaesthetic solution. SUMMARY:
      An adult male was referred to the University clinic 15 days after an inadvertent
      NaOCl injection into the palatal mucosa. Soft tissue necrosis was evident,
      without obvious bony involvement. Tissues healed without scarring within 30 days.
      No surgical intervention was required. KEY LEARNING POINTS: NaOCl is highly
      irritant when extruded into vital tissues.--Dentists should be careful to avoid
      the misuse of NaOCl, and should check the nature of any agent before injecting it
      into patients.--NaOCl should not be dispensed in a way that could allow it to be
      mistaken for local anaesthetic solutions.--The well-perfused tissues of the oral
      cavity have considerable healing ability.

PMID- 16454798
TI  - C-shaped root canal in a maxillary first molar: a case report.
AB  - AIM: This case report presents an unusual C-shaped root canal system in a
      maxillary first molar tooth. SUMMARY: Although C-shaped root canals are most
      frequently seen in the mandibular second molar, they may also appear in maxillary
      molars. A literature search revealed only a few case reports of C-shaped root
      canal systems in maxillary molars. The present case describes a C-shaped canal in
      the buccal root of a maxillary first molar. The endodontic access cavity
      displayed two canal orifices, one leading to the canal system in the buccal root,
      the other into the palatal root canal system. In the buccal root, what appeared
      to be the mesial and distal canals joined to form a single C-shaped canal. KEY
      LEARNING POINTS: --Careful examination of radiographs and the internal anatomy of
      teeth is essential.-- The location and morphology of root canals should be
      identified at high magnification under the microscope.

PMID- 16454799
TI  - Evidence for a stimulatory action of melanin-concentrating hormone on luteinising
      hormone release involving MCH1 and melanocortin-5 receptors.
AB  - The present series of studies aimed to further our understanding of the role of
      melanin-concentrating hormone (MCH) neurones in the central regulation of
      luteinising hormone (LH) release in the female rat. LH release was stimulated
      when MCH was injected bilaterally into the rostral preoptic area (rPOA) or medial
      preoptic area (mPOA), but not when injected into the zona incerta (ZI), of
      oestrogen-primed ovariectomised rats. In rats that were steroid-primed to
      generate a surge-like release of LH, MCH administration into the ZI blocked this
      rise in LH release: no such effect occurred when MCH was injected into the rPOA
      or mPOA. In vitro, MCH stimulated gonadotrophin-releasing hormone (GnRH) release
      from hypothalamic explants. Double-label immunohistochemistry showed GnRH
      immunoreactive neurones in the vicinity of and intermingled with immunoreactive
      MCH processes. MCH is the endogenous ligand of the MCH type 1 receptor (MCH1-R).
      Previously, we have shown a role for melanocortin-5 receptors (MC5-R) in the
      stimulatory action of MCH, so we next investigated the involvement of both MCH1-R
      and/or MC5-R in mediating the actions of MCH on GnRH and hence LH release. The
      stimulatory action of MCH in the rPOA was inhibited by administration of
      antagonists for either MCH1-R or MC5-R. However, in the mPOA, the action of MCH
      was blocked only by the MC5-R antagonist. LH release was stimulated by an agonist
      for MC5-R injected into the rPOA or mPOA; this was blocked by the MC5-R
      antagonist but not the MCH1-R antagonist. These results indicate that both MCH1-R
      and MC5-R are involved in the central control of LH release by MCH.

PMID- 16454800
TI  - Comparative analysis of immunoreactive cells for androgen receptors and oestrogen
      receptor alpha in copulating and non-copulating male rats.
AB  - In some species, including gerbils, guinea pigs, mice, rams and rats, some
      apparently normal males fail to mate. These kinds of animals have been named
      'noncopulating (NC)'. The cause of this behavioural deficit is unknown. The
      present study aimed to determine whether NC male rats have alterations in the
      amount of androgen (AR) and oestrogen receptor alpha (ERalpha) in a neuronal
      circuit important for the control of male sexual behaviour; the vomeronasal
      projection pathway. We evaluated the number of AR and ERalpha immunoreactive (AR
      IR and ERalpha-IR) cells in the accessory olfactory bulb (AOB), the bed nucleus
      of the stria terminalis (BNST), the anterior-dorsal medial amygdala (MeAD), the
      posterior dorsal amygdala (MePD) and the medial preoptic area (MPOA). The results
      demonstrate that the number of AR-IR cells in NC males was significantly higher
      compared to copulating (C) males in the MePD, but no significant differences were
      found in any of the other structures analysed. ERalpha-IR cells were more
      abundant in NC than in C males in the MeAD and the MePD. However, in the MPOA the
      number of ERalpha-IR cells was significantly reduced in NC males. No significant
      differences were found in the AOB or in the BNST. A similar pattern of results
      was observed when regions within these structures that are activated by Fos
      expression, on mating or exposure to sexually relevant cues were analysed. The
      differences in the number of AR and ER in particular brain areas could be
      associated with alterations in sexual behaviour as well as partner and olfactory
      preference for receptive females seen in NC male rats.

PMID- 16454802
TI  - Progesterone treatment of adult male rats suppresses arginine vasopressin
      expression in the bed nucleus of the stria terminalis and the centromedial
      amygdala.
AB  - The steroid sensitive vasopressin cells of the bed nucleus of the stria
      terminalis (BST) and centromedial amygdala (CMA) are involved in numerous
      behavioural and physiological functions. These cells are known to be greatly
      influenced by gonadal steroids. Castration reduces and testosterone replacement
      restores arginine vasopressin (AVP)-immunoreactive (-ir) labelling and AVP mRNA
      expression in the BST and CMA. Gonadal steroids appear to act directly in AVP
      expressing cells within the BST and CMA, because the majority of AVP-ir cells in
      these areas contain oestrogen and androgen receptor immunoreactivity. Recently,
      we have localised progestin receptor immunoreactivity in virtually all of the AVP
      ir cells in the BST and CMA. To understand the role played by progestin receptors
      in AVP cells within the BST and CMA, we treated male rats with 1 mg of
      progesterone or oil for 5 days, and then examined AVP immunoreactivity within the
      brain. We found that progesterone decreased AVP-ir labelling within the BST and
      CMA, as well as in two of the projection sites of these cells, the lateral septum
      and lateral habenula. Progesterone treatment did not alter testosterone secretion
      from the testes, nor did it alter adult male sexual behaviour. These data
      illustrate an additional mechanism by which the AVP cells in the BST and CMA can
      be regulated. These data also suggest that progesterone may act in the male brain
      to influence behaviours that are AVP-dependent.

PMID- 16454801
TI  - GABA(B) receptor-activation inhibits GABAergic synaptic transmission in
      parvocellular neurones of rat hypothalamic paraventricular nucleus.
AB  - The paraventricular nucleus of the hypothalamus contains three classes of
      neurones: (i) magnocellular and (ii) parvocellular neurosecretory neurones and
      (iii) nonendocrine projection neurones. The present study aimed to determine
      whether functional GABA(B) receptors are present on axon terminals that synapse
      with parvocellular neurosecretory and nonendocrine paraventricular neurones and
      to determine how activation of GABA(B) receptors control GABAergic input to these
      neurones. Whole-cell recordings were performed in coronal hypothalamic slices of
      the rat containing the paraventricular nucleus. GABA(A) receptor-mediated
      inhibitory postsynaptic currents (i.p.s.c.) were isolated pharmacologically in
      the presence of antagonists of glutamatergic ionotropic receptors. We found that
      baclofen, an agonist of GABA(B) receptors, decreased the frequency of spontaneous
      and miniature i.p.s.c. It also decreased the amplitude of evoked i.p.s.c. These
      effects were suppressed by CGP55845A, a competitive antagonist of GABA(B)
      receptors. CGP55845A also increased the frequency of miniature i.p.s.c. and the
      amplitude of evoked i.p.s.c., suggesting that, in physiological conditions,
      presynaptic GABA(B) receptors exert a tonic inhibition on GABA release. Baclofen
      had no effect on GABA-evoked postsynaptic currents, suggesting that the baclofen
      dependent suppression of GABAergic i.p.s.c. was exclusively due to a presynaptic
      action of the agonist. Our data indicate that GABA(B) receptors are present on
      axon terminals of GABAergic presynaptic neurones contacting parvocellular
      neurosecretory and nonendocrine paraventricular neurones, and suggest that
      GABA(B) receptors exert a tonic inhibition of GABA release from GABAergic
      terminals. Activation of these receptors causes disinhibition of parvocellular
      neurosecretory and nonendocrine paraventricular neurones.

PMID- 16454803
TI  - Rapid neural Fos responses to oestradiol in oestrogen receptor alphabeta double
      knockout mice.
AB  - The standard mode of action for oestradiol is via activation of nuclear oestrogen
      receptors (ERs), which initiate DNA transcription leading to protein formation.
      In the present study, we examined the rapid and potentially ER-independent action
      of oestradiol using Fos as a marker of neural activity. We assessed Fos
      immunoreactivity (ir) in brains of mice with functional versus nonfunctional ERs.
      Fos-ir was compared in brains of control mice that did and did not receive
      oestradiol treatment prior to sacrifice, and cell numbers in the preoptic area
      (POA), ventromedial nucleus of the hypothalamus (VMH), area 2 of cingulate cortex
      (CG2), granular layer of accessory olfactory bulb (Gr-AOB), olivary pretectal
      nucleus (OPT) and pyramidal layer of field CA3 of hippocampus (Py-CA3) were
      increased 90 min after oestradiol treatment. By contrast, in brains of double
      oestrogen receptor alphabeta knockout (ERalphabetaKO) female mice, no change in
      Fos-ir was noted after oestradiol treatment in the POA, VMH, Gr-AOB or Py-CA3,
      suggesting that these responses to oestradiol depend on ERalpha and/or ERbeta.
      However, Fos-ir was induced by oestradiol in the OPT and CG2 in ERalphabetaKO
      mice. These regions do not contain ERalpha-ir in control brains. In ERalphabetaKO
      brains as well, ERalpha-ir was absent, suggesting that the mutant ERalpha (E1)
      present in ERalphaKO brain is also absent in these regions. We speculate that
      oestradiol has rapid effects in the OPT and CG2 via a novel mechanism that does
      not require either classic oestrogen receptor.

PMID- 16454804
TI  - Triiodothyronine expands the lactotroph and maintains the lactosomatotroph
      population, whereas thyrotrophin-releasing hormone augments thyrotroph abundance
      in aggregate cell cultures of postnatal rat pituitary gland.
AB  - In the present study, we used a three-dimensional pituitary cell culture system
      from early postnatal rats to examine the in vitro developmental potential of
      triiodothyronine (T3) and thyrotrophin-releasing hormone (TRH). Cell types were
      identified at the hormone mRNA level by single-cell reverse transcription
      polymerase chain reaction and any change in abundance was further examined by
      immunofluorescence staining of the corresponding hormone protein. In aggregates
      from 14-day-old rats, long-term (12-16 days) treatment with T3 (0.5 nM) increased
      the abundance of cells expressing prolactin mRNA (PRLmRNA cells) by 2.5-fold and
      lowered that of nonhormonal cells and thyroid-stimulating hormone beta
      (TSHbeta)mRNA cells. The abundance of growth hormone (GH)mRNA cells decreased
      during culture compared to that in the freshly dispersed pituitary gland and T3
      did not significantly affect this cell population. Cells coexpressing PRL mRNA
      and GH mRNA virtually disappeared during culture but reappeared in the presence
      of T3. T3 increased the abundance of PRL-immunoreactive (ir) cells in aggregates
      from 14-day-old rats, as well as in aggregates from newborn and 1-week-old rats.
      As estimated by bromodeoxyuridine (BrdU) labelling, a 3-day treatment with T3
      enhanced the number of PRL-ir cells that had incorporated BrdU, but did not yet
      expand the total population of PRL-ir cells. Long-term treatment with TRH (100
      nM) did not affect the proportion of PRLmRNA or GHmRNA cells, but consistently
      increased the proportional number of TSHbeta(mRNA) and TSHbeta-ir cells. The
      present data confirm the findings obtained in recent in vivo loss of function
      genetic studies suggesting that T3 plays a prominent role in postnatal expansion
      of the lactotroph population and that TRH is important for thyrotroph
      development. The data suggest that the effect of T3 is brought about by a direct
      action on the pituitary gland through a cell proliferation mechanism. T3 also
      appears to support the lactosomatotroph population. In view of the established
      theory that lactotrophs develop from GH-expressing progenitor cells and that this
      is a post mitotic event, we propose that T3 is mitogenic for GHmRNA cells that
      lack GH-ir material and that transdifferentiate into PRL-ir cells, but that a
      pathway of PRL cell development from mitotic nonhormonal cell progenitors may
      also be involved.

PMID- 16454806
TI  - Anabolic steroids: a fatal attraction?
AB  - Anabolic-androgenic steroids (AAS) are widely abused, but the potential for
      dependence and addiction remains unclear. Recent studies from our laboratory have
      shown that male and female hamsters will voluntarily self-administer testosterone
      and other AAS. Furthermore, we have observed fatal androgen overdose during self
      administration. This suggests that AAS are potentially addictive, independent of
      their effects on muscle mass or athletic performance.

PMID- 16454805
TI  - Hypothalamic pro-GnRH-GAP, GnRH-I and GnRH-II during the onset of
      photorefractoriness in the white-crowned sparrow (Zonotrichia leucophrys
      gambelii).
AB  - Gambel's white-crowned sparrow is a long distance migrant that undergoes
      spontaneous gonadal regression as a result of long day exposure. This termination
      of breeding is caused by the development of photorefractoriness and the birds
      become insensitive to long days, including continuous light. The present study
      investigated its possible mechanisms by examining the activity of the
      gonadotrophin-releasing hormone (GnRH) system under different photoperiodic
      regimes. We investigated the localisation and distribution of GnRH-I, its
      precursor pro-GnRH-GAP and GnRH-II in Gambel's white-crowned sparrow brain using
      immunocytochemistry with specific antibodies during photostimulation and the
      development of photorefractoriness. The study revealed that photoperiodic
      treatment, including the onset of photorefractoriness, had no significant effect
      on the size or number of GnRH-I, pro-GnRH-GAP or GnRH II immunoreactive cells, or
      the density of the GnRH-I, pro-GnRH-GAP immunoreactive fibres at the median
      eminence. GnRH-II was not found in the median eminence, suggesting that it does
      not regulate pituitary gonadotrophin secretion. GnRH-I measurement in
      hypothalamic extracts by radioimmunoassay did not reveal any significant
      difference between birds that were photostimulated or in the early stages of
      photorefractoriness. Furthermore, the action of the excitatory amino acid
      glutamate agonist N-methyl-D-aspartate on GnRH neurones in photorefractory birds
      was demonstrated by the significant blockade of luteinising hormone release with
      a specific GnRH antagonist. Taken together, these results suggest that, in
      Gambel's white-crowned sparrow, a decrease in GnRH-I secretion is the initial
      step for the onset of photorefractoriness and not a decrease in GnRH-I
      biosynthesis.

PMID- 16454807
TI  - Pathogenesis of bone metastasis: a review.
AB  - BACKGROUND: Metastasic deposits from malignancies frequently lodge in the
      skeleton, including the jaw bones. METHOD: A review of the literature was
      performed in order to provide a coherent overview on the pathogenesis of bone
      metastasis. RESULTS: Bone metastasis follows complex molecular interactions that
      enable tumor cells to detach from the primary site, invade the extracellular
      matrix, intra-vasate, extra-vasate, and proliferate within bone. They induce
      local bone changes that could manifest radiologically as either osteolytic or
      radiodense. In addition to the direct bone changes, malignancies can elaborate
      mediators that are released in circulation, leading to generalized osteopenia.
      CONCLUSIONS: The spread of malignant neoplasms to bone is not a random process
      but rather a cascade of specific molecular events orchestrated through complex
      interactions between neoplastic cells and their environment.

PMID- 16454808
TI  - Correlation of basic fibroblast growth factor expression with the invasion and
      the prognosis of oral squamous cell carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the relationship between the
      expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor
      receptor-1 (FGFR-1) in cancer cells and fibroblasts at the invasive front of oral
      squamous cell carcinoma (OSCC), and the pathologic and clinical characteristics.
      METHODS: Sections of 61 biopsy specimens of primary OSCC were immunostained to
      assess the expression of bFGF and FGFR-1 in cancer cells and fibroblasts at the
      invasive front. RESULTS: The bFGF and FGFR-1 expressions in the cancer cells were
      evident in all specimens, whilst, in fibroblasts, they were detected in 41 (67%)
      of 61 specimens. These expressions in the fibroblasts occurred notably more often
      in high-invasive OSCC specimens than low-invasive OSCC specimens. The prevalence
      of bFGF and FGFR-1 expressions in cases with lymph node metastasis was
      significantly higher (P < 0.05) than in cases without metastasis. Moreover, these
      expressions were well correlated with patient prognosis. CONCLUSION: This study
      concludes that bFGF and FGFR-1 expressions in fibroblasts at the invasive front
      are linked to the mode of invasion and the prognosis in OSCC.

PMID- 16454809
TI  - Expression of Bcl-2 but not Bax has a prognostic significance in tongue
      carcinoma.
AB  - BACKGROUND: Among the molecular mechanisms involved in carcinogenesis, defects in
      the regulation of programmed cell death (apoptosis) make important contributions
      to the pathogenesis and progression of cancer. Apoptosis regulatory genes include
      the antiapoptotic bcl-2 gene and the proapoptotic bax gene. The aim of this study
      was to determine the spectrum of Bax and Bcl-2 expression, and to correlate these
      findings with clinicopathologic variables and prognosis. METHODS: In this study
      we have evaluated the immunohistochemical expression of Bcl-2 and Bax proteins in
      a series of 35 squamous cell carcinomas of the tongue. RESULTS: Immunoreactivity
      for Bax was detected in 37.1% and for Bcl-2 in 8.6% of cells, and for both
      proteins the staining was cytoplasmic and granular. Bcl-2 and Bax expression was
      mainly seen in peripheral cells of epithelial tumor islands with decreasing
      immunoreactivity toward the center of the neoplastic nests. Bax immunoexpression
      was significantly correlated with histologic grading (P=0.05), but not with the
      remaining clinicopathologic variables. Bcl-2 immunoreactivity was significantly
      correlated with N-stage (P=0.01) and survival. Patients with Bcl-2-negative
      tumors [mean survival: 73.97 months; 95% confidence interval (CI): 59-88] vs. Bcl
      2-positive ones (mean survival: 17.67 months; 95% CI: 6-29) had a longer survival
      (P=0.01; odds ratio=6.9). CONCLUSIONS: Bcl-2 is associated with aggressive
      disease, neck lymph node metastasis, and poor prognosis. Whereas Bax is related
      with histologic grade.

PMID- 16454810
TI  - Analysis of apoptosis-associated genes and pathways in oral cancer cells.
AB  - BACKGROUND: Cancer cells can resist apoptosis that is induced by stimuli such as
      detachment or differentiation, but may be more susceptible to apoptosis when
      exposed to chemotherapeutic drugs. The pattern of gene expression that produces
      this phenotype is unknown. METHODS: We compared gene expression patterns of
      normal human epidermal keratinocytes (NHEK cells) and the oral cancer cell line
      Tu183 when the cells were exposed to different apoptosis-inducing stimuli.
      RESULTS: Pathway analysis revealed that the phenotype difference could be best
      explained by the simultaneous existence of both proapoptosis and antiapoptosis
      signals in the cancer cells. Microarray analysis, supported by immunoblotting,
      showed that one gene that was likely to be involved in the proapoptosis signal
      was TNFRSF5, which encodes the receptor CD40. When Tu183 cells were exposed to
      the CD40 ligand they showed apoptosis, while NHEK cells did not. CONCLUSIONS: The
      effects of different apoptotic stimuli on normal cells and oral cancer cells can
      be explained by expression of proapoptosis genes, including the gene that encodes
      CD40.

PMID- 16454811
TI  - Osteonecrosis of the jaws in patients treated with bisphosphonates -
      histomorphologic analysis in comparison with infected osteoradionecrosis.
AB  - BACKGROUND: Patients treated with bisphosphonates because of bone metastases have
      been shown to develop osteonecrosis of the jaws. In the present study, we
      examined the histologic findings of these cases. As similarities between this
      disorder and infected osteoradionecrosis (IORN) are described, both lesions were
      compared. METHODS: We investigated eight patients with bisphosphonate treatment
      and osteonecrosis (four female, four male; median age: 65.6 years; cancer:
      multiple myeloma in five patients, breast cancer in three patients; mandibular
      involvement in five patients, maxillar involvement in three cases), and 10
      patients suffering from IORN (all male; median age: 61.3 years; cancer: squamous
      cell carcinoma in nine patients, adenoid cystic carcinoma in one patient;
      mandibular involvement in all cases). Multicentric and bilateral involvement was
      common in the bisphosphonate group. Histologically, the bone revealed diffuse and
      patchy areas of necrosis in the bisphosphonate group, while in IORN osteonecrosis
      was larger and not diffusely distributed. RESULTS: In all cases, we found
      Actinomyces attached to the necrotic bone tissue. In five of eight
      bisphosphonates cases, and in six of 10 IORN cases, numerous osteoclasts could be
      detected close to vital bone exhibiting signs of bone resorption.
      Pseudoepitheliomatous hyperplasia (PH) was revealed in five of eight
      bisphosphonate patients, and in seven of 10 IORN patients. CONCLUSION: We
      conclude that Actinomyces is involved in the chronic, non-healing inflammatory
      processes as a characteristic feature of both diseases. Together with the
      associated presence of increased osteoclast numbers, we suggest that both factors
      may be involved in osteolytic mechanisms.

PMID- 16454812
TI  - Expression of TNF-alpha in oral lichen planus treated with fluocinolone acetonide
      0.1%.
AB  - BACKGROUND: Oral lichen planus (OLP) is a common chronic inflammatory disease
      involving T cells-mediated immunity. Tumor necrosis factor (TNF)-alpha has been
      reported to be involved in the disease process. The purpose of this study was to
      investigate the effect of fluocinolone acetonide in orabase (FAO) 0.1% on the
      expression of TNF-alpha in patients with OLP. METHODS: Eighteen Thai patients
      with atrophic or erosive OLP were recruited. Biopsy specimens were taken before
      and 1 month after treatment with FAO 0.1% and sent for histopathologic
      examination where they were immunohistochemically stained with antibody to TNF
      alpha. Twenty normal mucosa specimens were identically processed. Oral squamous
      cell carcinoma tissue was used as a positive control for TNF-alpha expression,
      whereas OLP sections without primary antibody were served as negative control.
      RESULTS: Sixteen of 18 cases (88.89%) of OLP exhibited positive staining for TNF
      alpha. Most of the TNF-alpha was observed in the mononuclear cells. Ten cases
      (55.56%) of OLP demonstrated TNF-alpha expression in keratinocytes. The number of
      mononuclear cells positive for TNF-alpha before the treatment with FAO 0.1% in
      orabase was statistically higher than that after the treatment (P=0.000) and in
      the normal mucosa (P=0.000). Moreover, the number of mononuclear cells after
      treatment with FAO 0.1% in orabase was statistically lower than before the
      treatment (P=0.000). CONCLUSION: Our study exhibited that TNF-alpha may be
      associated with the immunopathogenesis of OLP in Thai patients and FAO 0.1% had
      an effect on the reduction of TNF-alpha expression.

PMID- 16454813
TI  - Expression profile of chemokines and chemokine receptors in epithelial cell
      layers of oral lichen planus.
AB  - BACKGROUND: To understand the immunopathological features of oral lichen planus
      (OLP), we analyzed the expression of chemokines in the epithelial cell layers.
      METHODS: Epithelia from OLP or healthy gingiva were collected by laser
      microdissection. The chemokine and chemokine receptor expressions in the
      epithelia were analyzed by DNA microarray. RESULTS: High levels of MIP
      3alpha/LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia.
      Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were
      also increased. Immunohistologial analysis showed that high numbers of Langerhans
      cells (LCs) were present in the epithelia of OLP. Lesional epithelia also
      expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP
      10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5). CONCLUSIONS:
      Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the
      lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells
      in OLP could be mediated by signaling pathways through CXCR3 and CCR5.

PMID- 16454814
TI  - Glandular odontogenic cyst in China: report of 12 cases and immunohistochemical
      study.
AB  - OBJECTIVE: The purpose of this study was to present 12 additional cases of
      glandular odontogenic cyst (GOC) in the Department of Oral Pathology, School of
      Stomatology, Wuhan University, People's Republic of China, and to investigate
      their immunohistochemical cytokeratins (CKs) expression in the epithelial
      components. METHODS: A total of 12 GOCs were reviewed clinically and
      radiographically, and immunohistologic CKs AE1, 7, 8/18, 10/13, 14, 16, 19 and 20
      were performed by using a standard biotin-streptavidin immunoperoxidase technique
      on paraffin sections. RESULTS: The present series showed that eight occurred in
      males and four in females. The mean age was 37.6 years with a peak incidence
      occurring in the third decades (six of 12). Mandibles were more affected than
      maxillas (7:5), especially anterior mandible (four of seven). Radiographically,
      ratio multilocular to unilocular radiolucencies was 5:7 usually with well-defined
      borders. Histologically, cystic spaces were lined by non-keratinized stratified
      epithelia containing focal plaque-like or whirlpool-like thickenings; surface
      epithelial layer-containing eosinophilic cuboidal cells; mucous cells; and mucin
      pools of microcystic areas in the epithelium. Immunohistochemistry showed that
      epithelium of GOCs stained for CKs AE1, 7, 8/18, 10/13, 14 and 19 with slight
      changes in their patterns, and no reaction to CKs 16 and 20. CONCLUSIONS: Most
      clinical and histologic features in this study were analogous to those reported
      west population, although with slight difference between them. Histologically,
      the morphology of the epithelium strongly suggested an odontogenic origin, and
      CKs expression of GOC was similar to that of odontogenic epithelium, suggesting
      histochemically that GOC might be derived from odontogenic epithelium.

PMID- 16454815
TI  - Immunohistochemical detection of retinoblastoma protein and E2 promoter-binding
      factor-1 in ameloblastomas.
AB  - BACKGROUND: To clarify the roles of cell cycle regulation in oncogenesis and
      cytodifferentiation of odontogenic tumors, expression of retinoblastoma protein
      (RB) and E2 promoter-binding factor-1 (E2F-1) was analyzed in ameloblastomas as
      well as in tooth germs. METHODS: Tissue specimens of 10 tooth germs, 40 benign
      ameloblastomas, and five malignant ameloblastomas were examined
      immunohistochemically with the use of antibodies against RB, E2F-1, and
      phosphorylated RB. Ki-67 antigen immunostaining was made as a marker of cell
      proliferation. RESULTS: Immunohistochemical reactivity for RB, E2F-1,
      phosphorylated RB, and Ki-67 was detected in the nuclei of odontogenic epithelial
      cells near the basement membrane in tooth germs and benign and malignant
      ameloblastomas. The number of cells positive for phosphorylated RB was nearly
      equal to or slightly less than the number of cells positive for RB or E2F-1. The
      number of Ki-67-positive cells was slightly more than the numbers of cell
      positive for RB, E2F-1, or phosphorylated RB. The levels of immunoreactivity for
      RB, E2F-1, phosphorylated RB, and Ki-67 were slightly higher in benign and
      malignant ameloblastomas than in tooth germs. Plexiform ameloblastomas showed
      significantly higher expression of RB than follicular ameloblastomas. Ki-67
      immunoreactivity was significantly higher in ameloblastic carcinomas than in
      metastasizing ameloblastomas. CONCLUSION: Similar immunoreactivity for RB, E2F-1,
      phosphorylated RB, and Ki-67 in tooth germs and ameloblastomas indicated cellular
      expression of phosphorylated RB and active-free E2F-1 in both normal and
      neoplastic odontogenic tissues. Expression of RB, E2F-1, and phosphorylated RB
      was considered to be involved in cell proliferation and differentiation of
      odontogenic epithelium via control of the cell cycle.

PMID- 16454816
TI  - Peripheral ameloblastic fibroma.
AB  - Peripheral ameloblastic fibroma is an exceedingly rare lesion. Only three reports
      could be found, two of which appeared in the Japanese literature. Here, we report
      a case of peripheral ameloblastic fibroma occurring in a 5-year-old girl. The
      diagnosis was made after careful microscopic examination, to exclude other
      lesions. The lesion was excised and has not recurred 1 year after removal.

PMID- 16454817
TI  - Nobel Prize in Medicine awarded to a Gastroenterologist in 2005.

PMID- 16454818
TI  - Colorectal cancer screening with fecal occult blood testing (FOBT): an
      international perspective.

PMID- 16454819
TI  - Does fecal occult blood test have a place for colorectal cancer screening in
      China in 2006?

PMID- 16454820
TI  - Fecal occult blood test screening in the United kingdom.

PMID- 16454821
TI  - The place of fecal occult blood test in colorectal cancer screening in 2006: the
      U.S. perspective.

PMID- 16454822
TI  - The impact of antireflux surgery on oxidative stress of esophageal mucosa caused
      by gastroesophageal reflux disease: 4-yr follow-up study.
AB  - BACKGROUND AND AIM: Oxidative stress to esophageal mucosa plays a key role in the
      pathogenesis of gastroesophageal reflux disease (GERD), Barrett's esophagus, and
      adenocarcinoma. We investigated whether successful antireflux surgery eliminates
      oxidative stress. METHODS: Oxidative stress of esophageal mucosa was measured in
      20 GERD patients, before antireflux surgery and 6 and 48 months after it, and
      compared with normal controls' mucosa (N = 9). Preoperatively, 12 of the 20 had
      erosive esophagitis or Barrett's metaplasia. Postoperatively, healing of GERD was
      verified with endoscopy and 24-h pH monitoring. We measured oxidative stress by
      myeloperoxidase activity (MPA), superoxide dismutase activity, and glutathione
      content (GSH) in distal esophagus samples from endoscopy. RESULTS: No patient had
      reflux symptoms after surgery, and pH measurements had normalized. MPA in the
      distal esophagus decreased (p < 0.05) after successful antireflux surgery, but
      remained higher than that of controls both 6 months and 4 yr postoperatively (p <
      0.05). At all time-points, MPA was higher in patients with preoperatively
      detected erosive reflux disease (ERD) as compared to non-erosive reflux disease
      (NERD) (p < 0.01, p < 0.05, and p < 0.05, respectively). GSH values decreased
      with time only in NERD. At all time-points, GSH levels in distal esophagus were
      lower than control levels. CONCLUSIONS: Antireflux surgery can heal macroscopic
      esophagitis but cannot fully reverse the oxidative stress (as reflected by MPA
      and GSH) upon the distal esophageal mucosa.

PMID- 16454823
TI  - Association between weight gain and symptoms of gastroesophageal reflux in the
      general population.
AB  - BACKGROUND AND AIM: Excess weight is a risk factor of gastroesophageal reflux
      symptoms (GERS) in population-based studies but it is unknown to what extent
      short-term weight gain (occurring in months) is associated with the development
      of GERS. Our aim is to examine the association of weight gain with GERS. METHODS:
      A phone interview was conducted with 2,500 persons aged 40-79 yr selected at
      random from the general population of Spain. The Gastroesophageal Reflux
      Questionnaire was used to identify the onset, frequency, and severity of GERS. We
      also assessed weight, height, and 1-yr weight change (classified as no weight
      gain, weight gain < or =5 kg, and weight gain >5 kg). We compared the frequency
      of new (less than 1 yr duration) and old (1 yr or more duration) GERS among
      weight change subgroups. The association between weight change and GERS was
      analyzed by logistic regression adjusting for BMI and other potential
      confounders. RESULTS: The prevalence of new and old GERS, respectively, was
      significantly (p < 0.05) higher in subjects with weight gain >5 kg (14.4% and
      32.4%) than in those with weight gain < or =5 kg (8.2% and 27.5%) and no weight
      gain (5.4% and 22.5%). Subjects with a weight gain < or =5 kg showed an adjusted
      odds ratio (aOR) of 1.5 (95% confidence limits [CL]: 0.9-2.4) for new GERS and of
      1.1 (95% CL: 0.8-1.4) for old GERS. Those with a weight gain >5 kg showed an aOR
      of 3.0 (95% CL: 1.6-6.0) for new GERS and of 1.3 (0.8-2.1) for old GERS.
      CONCLUSION: Weight gain is associated with GERS, independently of BMI.

PMID- 16454824
TI  - A comparison between low-volume referring regional centers and a high-volume
      referral center in quality of preoperative metastasis detection in esophageal
      carcinoma.
AB  - BACKGROUND AND AIM: An inverse correlation between hospital volume and esophageal
      resection mortality has been reported. In this study, we compared the quality of
      preoperative metastasis detection between a high-volume referral center with that
      of low-volume referring regional centers. METHODS: In 573 patients diagnosed with
      esophageal cancer (1994-2003), the results of preoperative staging investigations
      (CT-scan, ultrasound of abdomen and neck, and chest x-ray) performed in 61
      regional centers were re-evaluated and/or repeated in one referral center. The
      gold standards were a radiological result with > or =6 months follow-up, fine
      needle aspiration, or the postoperative TNM-stage. RESULTS: In the same group of
      patients, the preoperative investigations performed in regional centers detected
      true-positive malignant lymph nodes in 8% of patients and true-positive distant
      metastases in 7% of patients, whereas these percentages were 16% and 20%,
      respectively, in the referral center. In 72/573 (13%) patients, one or more
      metastases detected in the referral center had been missed in the regional
      centers. After allowing resectability in the presence of M1a lymph nodes, this
      would still have resulted in futile esophageal resections in 6% of patients. In
      contrast to the higher diagnostic sensitivity in the referral center, specificity
      was comparable between referral and regional centers. CONCLUSIONS: This study
      found that, in assessing the operability of esophageal cancer, the diagnostic
      sensitivity of metastasis detection in a high-volume referral center was higher
      than that in referring regional centers. This resulted from both better CT
      scanning equipment and more experienced radiologists in the referral center.
      Should the decision to perform esophagectomy have only been based on metastasis
      detection in these regional centers, over 1 in 20 patients would have undergone
      resection in the presence of metastases.

PMID- 16454825
TI  - Third-line rescue therapy with levofloxacin after two H. pylori treatment
      failures.
AB  - AIM: Eradication therapy with proton pump inhibitor, clarithromycin and
      amoxicillin fails in a considerable number of cases. A rescue therapy still fails
      in more than 20% of the cases. Our aim was to evaluate the efficacy and
      tolerability of a third-line levofloxacin-based regimen in patients with two
      consecutive Helicobacter pylori eradication failures. METHODS:  DESIGN:
      Prospective multicenter study. PATIENTS: In whom a first treatment with
      omeprazole-clarithromycin-amoxicillin and a second with omeprazole-bismuth
      tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics)
      had failed. INTERVENTION: A third eradication regimen with levofloxacin (500 mg
      b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed
      for 10 days. OUTCOME: Eradication was confirmed with 13C-urea breath test 4-8 wk
      after therapy. RESULTS: One-hundred patients were initially included, and nine
      were lost for follow-up. All patients but five took all the medications
      correctly. Per-protocol and intention-to-treat eradication rates were 66% (95% CI
      = 56-75%) and 60% (50-70%). Adverse effects were reported in 25% of the patients,
      mainly including metallic taste (8%), nausea (8%), myalgia/arthralgia (5%), and
      diarrhea (4%); none of them were severe. CONCLUSION: Levofloxacin-based rescue
      therapy constitutes an encouraging empirical third-line strategy after multiple
      previous H. pylori eradication failures with key antibiotics such as amoxicillin,
      clarithromycin, metronidazole, and tetracycline.

PMID- 16454826
TI  - The association between the interleukin-1 polymorphisms and gastric cancer risk
      depends on the family history of gastric carcinoma in the study population.
AB  - OBJECTIVES: The association between interleukin-1 polymorphisms, H. pylori and
      increased gastric cancer risk remains controversial. AIMS: To compare the
      prevalence of these polymorphisms in individuals with two mutually exclusive
      diseases connected with infection, gastric cancer, and duodenal ulcer. METHODS:
      121 gastric cancer and 119 duodenal ulcer patients. Genomic DNA was typed for
      polymorphisms at position -511, -31 in the interleukin-1beta gene (IL-1 beta)
      using primer extension and mass-spectrometry. Analysis of the variable number of
      tandem repeats in intron 2, in its receptor antagonist gene (IL-1RN) was
      performed by PCR and agarose gel electrophoresis. RESULTS: All subjects were
      successfully genotyped for the three gene loci. IL-1 beta-511 was found to be in
      reverse linkage disequilibrium with IL-1 beta-31. The differences between gastric
      cancer and duodenal ulcer patients concerned only heterozygous variant of IL
      1beta and were related to family history of gastric cancer, tumor stage,
      histology, site. Thus, CT carriers were found to have a higher risk of sporadic
      [OR 2.21 (95% CI, 1.22-3.99)], early [OR 2.81 (95% CI, 1.14-6.93)], diffuse [OR
      2.48, (95% CI 1.21-5.09)] or non-cardia gastric cancer [OR 1.88 (95% CI 1.06
      3.33)]. Furthermore, CT genotype was significantly more prevalent in gastric
      cancer patients with negative than in those with a positive family history (p =
      0.039). CONCLUSIONS: The association between the interleukin-1 polymorphisms and
      gastric cancer risk depends on the family history of gastric carcinoma in the
      study population. This phenomenon may be in part responsible for differences in
      results of interleukin-1 studies performed on populations with low and high
      gastric cancer prevalence.

PMID- 16454827
TI  - The prevalence rate and anatomic location of colorectal adenoma and cancer
      detected by colonoscopy in average-risk individuals aged 40-80 years.
AB  - BACKGROUND: The role of screening colonoscopy for colorectal (CR) neoplasia in
      average-risk population, remains to be determined. OBJECTIVES: To evaluate the
      prevalence and anatomic location of CR adenoma and carcinoma and the morbidity of
      colonoscopy in individuals at average risk for CR cancer (CRC). METHODS: A
      retrospective prevalence study of subjects aged 40-80 yr, with no cancer-related
      symptoms, personal or family history of CR neoplasia, who underwent a
      colonoscopy. RESULTS: Enrolled were 1,177 persons; 183 aged 40-49 yr (young), 917
      aged 50-75 yr, and 77 aged 76-80 yr (elderly). The prevalence of overall CR
      neoplasia, advanced neoplasia, and cancer was 20.9%, 6.3%, and 1.1%,
      respectively. In the 50-75 age group, the prevalence of overall adenoma, advanced
      neoplasia, and cancer was 21.3%, 6.7%, and 1.2%, respectively. Of the 206
      neoplasia cases, 21-43% harbored proximal neoplasia beyond the reach of
      sigmoidoscopy, without distal lesions. Among the elderly, the prevalence of
      overall adenoma, advanced neoplasia, and cancer reached 26.0%, 14.3%, and 2.6%,
      respectively. In the young group, 9.8% had overall neoplasia, 1.1% had advanced
      adenoma, and none had CRC. Procedure-related morbidity rate was 0.1%, with no
      perforations, bleedings, or mortality. CONCLUSIONS: Screening colonoscopy in
      average-risk subjects demonstrated a considerable prevalence of CR neoplasia and
      proximal lesions beyond the reach of sigmoidoscopy. The morbidity rate was
      negligible. Primary screening colonoscopy should be considered in health programs
      for the average-risk population, beginning at the age of 50 yr. The significantly
      high rate of advanced and proximal neoplasia in the elderly, encourages the
      inclusion of healthy subjects aged 76-80 yr in future prospective studies.

PMID- 16454828
TI  - The case for direct colonoscopy screening for colorectal cancer.
AB  - Recent large series of direct colonoscopy screening for colorectal cancer
      increase our understanding of the advantages of this approach, and have
      indirectly confirmed efficacy. When performed by well-trained, experienced
      endoscopists, colonoscopy screening is successful and safe. The prevalence of
      advanced neoplasia is low under the age of 50 yr but increases substantially with
      each decade of life thereafter at least until the age of 80 yr. Most detected
      cancers are at an early, curable stage. A substantial number of proximal advanced
      neoplasia are detected that would be missed by screening flexible sigmoidoscopy.
      Widespread population-based colonoscopy screening would markedly decrease the
      incidence and mortality of this major malignancy. Issues of compliance and
      capacity related to direct colonoscopy have not yet been adequately addressed.

PMID- 16454829
TI  - Prospective endoscopic ultrasonographic evaluation of the frequency of
      nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple
      endocrine neoplasia type 1.
AB  - BACKGROUND: The frequency of pancreaticoduodenal endocrine tumors in patients
      with multiple endocrine neoplasia type 1 (MEN1) remains unknown. AIM: To evaluate
      prospectively with endoscopic ultrasonography (EUS) the frequency of
      nonfunctioning (asymptomatic) pancreaticoduodenal tumors. PATIENTS AND METHODS:
      MEN1 patients without functioning pancreatic involvement underwent systematic
      pancreaticoduodenal EUS in nine GTE (Groupe des Tumeurs Endocrines) centers.
      Demographic and clinical factors predictive of pancreatic involvement were
      sought, and standardized biochemical measurements obtained. RESULTS: Between
      November 1997 and July 2004, 51 patients (median age: 39 [range: 16-71] yr) were
      studied. MEN1 had been diagnosed 3 [0-20] yr earlier, notably by genetic
      screening for 26 (51%) with asymptomatic disease. Twenty-five patients had minor
      biochemical anomalies (<2 x normal (N)) and serum somatostatin was 10.8 N in 1;
      EUS detected pancreatic lesions in 28 patients (54.9%; 95% CI: 41.3-68.7%). A
      median of three [1-9] tumors with a median diameter of 6 [2-60] mm was found per
      patient; for 19 (37.3%) patients a tumor measured > or =10 mm and > or = 20 mm in
      7 (13.7%) patients. Only one duodenal lesion was found and three patients had
      peripancreatic adenopathies. Pancreatic tumors were not associated with any of
      the studied parameters, notably age, family history, biochemical anomalies.
      Sixteen of twenty-six patients underwent EUS monitoring over 50 [12-70] months;
      six (37.5%) had more and/or larger pancreatic lesions. CONCLUSION: The frequency
      of nonfunctioning pancreatic endocrine tumors is higher (54.9%) than previously
      thought. The size and number of these tumors can increase over time. Pancreatic
      EUS should be performed once MEN1 is diagnosed to monitor disease progression.

PMID- 16454831
TI  - Endoscopic gallbladder stent placement for treatment of symptomatic
      cholelithiasis in patients with end-stage liver disease.
AB  - OBJECTIVES: Symptomatic cholelithiasis is a common disease in the general
      population with an increased prevalence in patients with cirrhosis. While
      cholecystectomy is the procedure of choice for the treatment of symptomatic
      cholelithiasis, cirrhotics have an increased risk of complications associated
      with this therapy. We have found that placement of an endoscopic gallbladder
      stent is an alternative, less invasive treatment for cirrhotic patients with
      symptomatic gallbladder disease and describe our experience here. METHODS: A
      retrospective medical record review of 23 patients with cirrhosis who underwent
      endoscopic retrograde cholangiography with gallbladder stent placement for
      symptomatic gallbladder disease from July 1994 to August 2004. RESULTS:
      Indications for stent placement included recurrent biliary colic (56.5%), acute
      calculous cholecystitis (39%), acalculous cholecystitis (8.6%), and gallstone
      pancreatitis (8.6%). All patients experienced resolution of their symptoms
      following stent placement. Twenty patients (87%) were asymptomatic from 5 days to
      3 years post-procedure until transplantation, death, or end of study period. Nine
      patients (39%) underwent liver transplantation, 5 days to 34 months after the
      procedure. Eleven patients are well, with ten patients awaiting liver
      transplantation. Three patients developed late complications and were treated
      successfully with antibiotics. CONCLUSION: Endoscopic stenting of the gallbladder
      may be a potential treatment for symptomatic gallbladder disease in patients with
      cirrhosis awaiting liver transplantation, considered to be high-risk for
      cholecystectomy.

PMID- 16454830
TI  - Nasopharyngeal decolonization of methicillin-resistant Staphylococcus aureus can
      reduce PEG peristomal wound infection.
AB  - OBJECTIVES: The aim of this study is to determine whether nasopharyngeal
      decolonization of methicillin-resistant Staphylococcus aureus (MRSA) can reduce
      peristomal wound infection shortly after percutaneous endoscopic gastrostomy
      (PEG) placement. METHODS: Of the 84 hospitalized patients referred for PEG, 72
      were enrolled in a one-third observation (Group A) and two-thirds in a randomized
      trial (Groups B and C). Nasopharyngeal swabs were taken from a consecutive series
      of patients prior to PEG insertion. Based upon these results, they were
      classified into three groups: Group A, MRSA-negative (n = 24), Group B, MRSA
      positive, but not eradicated (n = 24), Group C, MRSA-positive and eradicated with
      intranasal application of mupirocin, arbekacin inhalation, and oral
      sulfamethoxazole/trimethoprim (n = 24). The standard PEG pull-through insertion
      technique was performed on all 72 patients. All patients received prophylactic
      and concomitant antibiotics. Infections at the peristomal site were prospectively
      evaluated and defined as having at least two of the following conditions:
      peristomal erythema, induration, and purulent discharge. Bacterial culture using
      purulent discharge was performed. RESULTS: There was significant difference in
      the peristomal infection rates among the groups: Group A, 0% (0/0); Group B, 100%
      (24/24); Group C, 8% (2/24) (p < or = 0.0001). In Group C, nasopharyngeal
      decolonization of MRSA, which was achieved by the combination of intranasal
      mupirocin, arbekacin inhalation, and oral sulfamethoxazole/trimethoprim in all 24
      patients, significantly reduced peristomal infections. Eighteen (16 in Group B
      and 2 in Group C) of these 26 infected patients had cellulitis and developed
      purulent discharge from which MRSA was isolated. CONCLUSIONS: Nasopharyngeal
      decolonization of MRSA can reduce peristomal infection shortly after the pull
      through PEG insertion. MRSA appears to be a major pathogen in PEG peristomal
      infection while prophylactic and concomitant antibiotics are being used.

PMID- 16454832
TI  - Is there a role for cholangioscopy in patients with primary sclerosing
      cholangitis?
AB  - OBJECTIVES: Assess the role of cholangioscopy in primary sclerosing cholangitis
      for 1) detection of cholangiocarcinoma using cholangioscopy-assisted biopsy 2)
      detection of stones not seen on cholangiography 3) stone removal with
      cholangioscopy-directed lithotripsy. METHODS: Prospective cohort of consecutive
      patients referred for cholangioscopy to evaluate dominant strictures or stones. A
      data collection sheet was employed. Follow-up was by chart review/phone contact.
      Clinical improvement was defined as resolution of jaundice or > or =50% reduction
      in pain or cholangitis episodes requiring hospitalization. RESULTS: 41 patients
      (30M, 11F) had 60 cholangioscopy procedures (55 per oral, 5 percutaneous). 33/41
      (80%) patients underwent 44 tissue sampling events. HISTOLOGY: positive for
      extrahepatic cholangiocarcinoma (N = 1), negative/atypical (N = 31), and
      inadequate (N = 1). Stones were found in 23/41 (56%) patients, of which 7/23
      (30%) were missed on cholangiography and detected only by cholangioscopy. 9/23
      (39%) underwent cholangioscopy-directed lithotripsy. Stone clearance: complete (N
      = 10, 7 by cholangioscopy-directed lithotripsy after failed conventional stone
      extraction); partial (N = 7); and not attempted (N = 6). Median follow-up was
      17.0 months (range 1-56). Clinical improvement was achieved in 25/40 (63%). Eight
      patients have undergone transplant and cholangiocarcinoma was present in the
      explant of two at 1 and 12 months post-cholangioscopy, respectively. CONCLUSIONS:
      This is the first series of patients with primary sclerosing cholangitis
      undergoing cholangioscopy for the evaluation of dominant strictures and
      cholangioscopy-directed stone therapy with demonstrable clinical benefits. Stones
      detected by cholangioscopy were missed by cholangiography in nearly one of three
      patients. Cholangioscopy-directed lithotripsy may be superior to conventional
      ERCP for achieving complete stone clearance. Despite the use of cholangioscopy,
      diagnosis of cholangiocarcinoma remains technically challenging.

PMID- 16454833
TI  - Epidemiology and clinical features of sporadic hepatitis E as compared with
      hepatitis A.
AB  - OBJECTIVES: To compare the epidemiology and clinical features of two enterically
      transmitted hepatitis, namely hepatitis E and hepatitis A. METHODS: We analyzed
      clinical features and risk factors of 105 cases of hepatitis A and 24 cases of
      hepatitis E admitted in 2002. All patients were tested positive for IgM antibody
      against either hepatitis A virus (HAV) or hepatitis E virus (HEV), and all
      patients were tested to be negative for IgM anti-HBV or IgG anti-HCV. RESULTS:
      Hepatitis A patients were significantly younger (median age = 27 yr) and most had
      a recent history of shellfish consumption, whereas hepatitis E patients were
      older (median age = 53 yr) and most had a recent travel history. Whereas
      hepatitis A was milder and recovery was uneventful, hepatitis E was more severe,
      associated with significant mortality and frequently complicated by protracted
      coagulopathy and cholestasis. CONCLUSIONS: Hepatitis E is a more severe disease
      entity as compared with hepatitis A and significant proportion of them are
      imported cases from an endemic area.

PMID- 16454834
TI  - Treatment with Peg-interferon alpha-2b for HBeAg-positive chronic hepatitis B:
      HBsAg loss is associated with HBV genotype.
AB  - BACKGROUND AND AIMS: Hepatitis B surface antigen (HBsAg) loss is the hallmark of
      a complete response to antiviral therapy for chronic hepatitis B. In this study,
      we investigated the frequency of HBsAg loss after treatment with pegylated (Peg)
      interferon alpha-2b. METHODS: In a multicenter randomized controlled trial, 266
      HBeAg-positive patients were treated for 52 wks with Peg-interferon alpha-2b (100
      microg/wk) in combination with either lamivudine (100 mg/day) or placebo.
      Posttreatment follow-up was 26 wks. RESULTS: At the end of follow-up, 95 (36%) of
      the 266 patients exhibited HBeAg loss, 18 (7%) HBsAg loss, and 16 (6%) HBsAg
      seroconversion. Addition of lamivudine did not enhance HBeAg loss, HBsAg loss, or
      development of anti-HBs. All 18 patients who showed HBsAg loss had normal ALT; 11
      (61%) of these patients were also hepatitis B virus (HBV) DNA negative (<400
      copies/mL) at the end of follow-up. Loss of HBsAg differed according to HBV
      genotype: 14% for genotype A, 9% for genotype B, 3% for genotype C, and 2% for
      genotype D (A vs D: p = 0.006). CONCLUSIONS: One year of Peg-interferon alpha-2b
      for HBeAg-positive patients led to HBsAg loss in 7%. Our study indicates that
      treatment with Peg-interferon alpha-2b is the best therapy to achieve HBsAg
      clearance in patients with genotype A.

PMID- 16454835
TI  - HFE genotypes in decompensated alcoholic liver disease: phenotypic expression and
      comparison with heavy drinking and with normal controls.
AB  - OBJECTIVES: Predisposition to alcoholic liver disease (ALD) may be partly
      genetic. Heterozygosity for the HFE mutations C282Y and/or H63D has been
      associated with more severe disease in several liver conditions. Studies in ALD
      have not used controls matched for alcohol consumption and results have been
      conflicting. METHODS: HFE genotyping was performed in two Caucasian heavy
      drinking cohorts (>60 units/wk (M) or 40 units/wk (F) for >5 yr): (a) 254
      patients with decompensated ALD (Child's grade B or C), (b) 130 controls with
      similar alcohol consumption but without liver disease. Results in males were also
      compared with those from another study of healthy male blood donors. RESULTS: (1)
      Genotype distributions for the C282Y and H63D mutations were similar in ALD
      patients, heavy-drinking controls, and healthy blood donors. (2) ALD patients
      with and without HFE mutations had similar disease severity, age at presentation,
      and alcohol consumption. (3) Increased serum ferritin and % transferrin
      saturation were seen in 63% and 29% of ALD patients, regardless of HFE genotype;
      the increased % transferrin saturation was due to reduced unsaturated iron
      binding capacity, rather than increased serum iron. (4) Stainable liver iron was
      present in 52% of patients; grade was greater in patients with two HFE mutations
      than in those with one or with none. (5) Only the two C282Y homozygote patients
      had substantial iron overload. CONCLUSIONS: Although serum iron abnormalities are
      common, C282Y and H63D mutation frequencies were not increased in heavy drinkers
      with decompensated liver disease. HFE mutations, although modestly influencing
      liver iron, do not predispose to clinically significant ALD.

PMID- 16454836
TI  - The gastrointestinal safety and effect on disease activity of etoricoxib, a
      selective cox-2 inhibitor in inflammatory bowel diseases.
AB  - BACKGROUND: While traditional nonsteroidal antiinflammatory drugs (t-NSAIDs) are
      relatively contraindicated in patients with inflammatory bowel disease (IBD) for
      fear of disease aggravation, controlled clinical trials showed that cyclo
      oxygenase-2 inhibitors have fewer gastrointestinal side effects than the t
      NSAIDs. Etoricoxib is a new antiinflammatory inhibitor that has high Cox-2
      selectivity. OBJECTIVES: To assess the safety of etoricoxib and effect on disease
      activity in patients with IBD in a multicenter, double-blind, placebo-control
      study. METHODS: Study group included 76 patients suffering from IBD (ulcerative
      colitis (UC) (38), and Crohn's disease (CD) (38)). The control group included 70
      patients known to have UC (35) and Crohn's disease (CD) (35). Patients of both
      groups were referred to the rheumatology clinic for rheumatic manifestations that
      require antiinflammatory therapy and were intolerable to the t-NSAIDs. The level
      of the IBD activity at the baseline visit, when drug/placebo therapy was
      initiated, was scored for all subjects included in the study. In the study group
      the dose of etoricoxib ranged from 60 to 120 mg tablet once a day according to
      their rheumatic condition. The control group received a placebo tablet once a
      day. Adverse events related to the use of the study medication in 1 and 3 months
      time were documented. Etoricoxib/placebo therapy was stopped once the patient
      experience flare up of their IBD. RESULTS: There was no significant difference
      between the patients and the control groups. After 3 months of etoricoxib
      therapy, 8 of 76 (10.53%) of the study group had aggravation of their underlying
      IBD and stopped the drug therapy, while 68 of 76 (89.5%) completed the study. The
      mean disease activity index before etoricoxib therapy was 1.15 + 0.794, whereas
      it was 1.19 + 0.683 after therapy. In the control group 8 of 70 (11.43%)
      experienced exacerbation of their symptoms while 62 of 70 (88.6%) completed the
      study. In the control group the mean disease activity before treatment was 1.16 +
      0.253, whereas after placebo therapy was 1.20 + 0.481. 67 of 76 (88.2%) of the
      study group and 62 of 70 (88.6%) of the control group gave history of using t
      NSAID therapy in addition to PPI that caused flare up of their IBD. For the
      patients who had to stop their drug therapy, all the adverse events occurred in
      the first month of drug/placebo challenge and all symptoms were reversible.
      CONCLUSION: Etoricoxib therapy is safe and beneficial in most patients with IBD
      treatment with etoricoxib was not associated with exacerbation of the underlying
      IBD- and GI-related complications.

PMID- 16454837
TI  - Contribution of IBD5 locus to clinical features of IBD patients.
AB  - AIM: The aim of this study was to investigate the influence of the IBD5 locus on
      clinical features of inflammatory bowel disease (IBD) patients, and its possible
      interaction with the CARD15 gene. PATIENTS AND METHODS: A cohort of 1,199 IBD
      patients (570 with CD and 629 with ulcerative colitis [UC]), and 357 healthy
      subjects were investigated. Information on clinical features was fully available
      for 855 IBD patients. Two SNPs in the IBD5 locus (IGR2198a_1 and IGR2096a_1) and
      the three major variants of CARD15 gene were genotyped in patients and controls.
      RESULTS: Homozygous carriers of risk alleles were significantly more frequent in
      CD (22.6% for IGR2198a_1, OR = 1.6, p = 0.015; 21.9% for IGR2096a_1, OR = 1.6, p
      = 0.012) compared to controls (16.8% and 15.7%, respectively). The homozygote
      frequency was also increased in UC patients, but not significantly. No
      significant gene-gene interaction was detected between IBD5 and CARD15. A
      univariate analysis detected association between IBD5 and steno/fistulizing
      behavior in CD patients (OR = 1.9; p = 0.004), and presence of more extensive
      colitis in UC patients (OR = 1.7; p = 0.01). Results from multiple logistic
      regression, after correction for covariates, showed that the influence of IBD5 on
      clinical outcome of CD was completely masked by that of CARD15, while the
      influence on more extensive colitis in UC patients was confirmed. CONCLUSIONS:
      Our study shows that presence of the IBD5 risk alleles, particularly in the
      homozygous state, is associated with IBD and especially with CD, without a
      significant epistasis with CARD15. The contribution of CARD15 risk alleles to CD
      clinical features is prominent on that of IBD5.

PMID- 16454838
TI  - A randomized double-blind placebo-controlled trial of rifaximin in patients with
      abdominal bloating and flatulence.
AB  - AIMS: To study the efficacy of rifaximin, a nonabsorbable antibiotic, in
      relieving chronic functional symptoms of bloating and flatulence. METHODS:
      Randomized double-blind placebo-controlled trial consisting of three 10-day
      phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo
      (phase 2), and post-treatment period (phase 3). Primary efficacy variable was
      subjective global symptom relief at the end of each phase. A symptom score was
      calculated from a symptom diary. Lactulose H2-breath test (LHBT) was performed at
      baseline and end of study. RESULTS: One hundred and twenty-four patients were
      enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable
      and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and
      54.1%, respectively. At the end of phase 2, there was a significant difference in
      global symptom relief with rifaximin versus placebo (41.3% vs 22.9%, p = 0.03).
      This improvement was maintained at the end of phase 3 (28.6% vs 11.5%, p = 0.02).
      Mean cumulative and bloating-specific scores dropped significantly in the
      rifaximin group (p < 0.05). Among patients with IBS, a favorable response to
      rifaximin was noted (40.5% vs 18.2%; p = 0.04) persisting by the end of phase 3
      (27% vs 9.1%; p = 0.05). H2-breath excretion dropped significantly among
      rifaximin responders and correlated with improvement in bloating and overall
      symptom scores (p = 0.01). No adverse events were reported. CONCLUSIONS:
      Rifaximin is a safe and effective treatment for abdominal bloating and
      flatulence, including in IBS patients. Symptom improvement correlates with
      reduction in H2-breath excretion. Future trials are needed to examine the
      efficacy of long-term or cyclic rifaximin in functional colonic disorders.

PMID- 16454839
TI  - Germs, gas and the gut; the evolving role of the enteric flora in IBS.
AB  - Gas-related symptoms are common in irritable bowel syndrome (IBS), though their
      pathophysiology remains poorly understood, various studies invoking increased gas
      production, impaired gas transit, and increased sensitivity to gas. Recent
      evidence suggests a potential role for bacterial overgrowth in some patients with
      IBS; the study discussed herein provides further support for this concept by
      describing an amelioration of bloating and flatulence following a short course of
      the poorly absorbed antibiotic, rifaximin.

PMID- 16454840
TI  - Detailed characterization of epidemiology of uninvestigated dyspepsia and its
      impact on quality of life among African Americans as compared to Caucasians.
AB  - BACKGROUND AND AIMS: We wished to study the prevalence as well as the
      sociodemographic characteristics and quality of life (QoL) of African American
      patients with uninvestigated dyspepsia (UD) among the population at large and
      compare it to the Caucasians. METHODS: A total of 990 adults from nine different
      sites in the Jackson, Mississippi metropolitan area (670 African Americans and
      320 Caucasians), completed self-administered questionnaires providing
      sociodemographic information, and details regarding bowel habits and associated
      symptoms for diagnosing the presence or absence of UD based on ROME II criteria.
      QoL was assessed by the SF-12 questionnaire. RESULTS: Of the 990 participants 247
      had UD, giving a total sample prevalence of 24.9% (African Americans = 24.3%,
      Caucasians = 26.2%). Adjusting for other risk factors in a reduced logistic
      regression model, we found female sex (OR 1.8; CI 1.2-2.6; p < 0.01), lower
      education (p < 0.01), and larger size of household (p = 0.01) to be important
      correlates of UD prevalence whereas the lower household income showed a trend
      toward statistical significance (p = 0.057). Using the adjusted odds ratio as an
      estimate of relative risk, Caucasians were 1.5 (95% CI = 11.1-2.1; p = 0.017)
      more likely than African Americans to have UD. In terms of an index for QoL on SF
      12 (possible score = 1-44, with 44 being ideal), the adjusted mean score was
      significantly lower for adults with UD compared to non-UD adults (30.4 vs 35.0; p
      < 0.01). However, there was no difference in impairment of life in Caucasians
      versus African Americans (32.9 vs 32.5; p = 0.36). CONCLUSIONS: UD occurs less
      frequently among African Americans. While UD affects QoL among both Caucasians
      and African Americans, the degree of impairment is similar.

PMID- 16454841
TI  - Polyp miss rate determined by tandem colonoscopy: a systematic review.
AB  - BACKGROUND AND AIMS: Colonoscopy is the best available method to detect and
      remove colonic polyps and therefore serves as the gold standard for less invasive
      tests such as virtual colonoscopy. Although gastroenterologists agree that
      colonoscopy is not infallible, there is no clarity on the numbers and rates of
      missed polyps. The purpose of this systematic review was to obtain summary
      estimates of the polyp miss rate as determined by tandem colonoscopy. METHODS: An
      extensive search was performed within PUBMED, EMBASE, and the Cochrane Library
      databases to identify studies in which patients had undergone two same-day
      colonoscopies with polypectomy. Random effects models based on the binomial
      distribution were used to calculate pooled estimates of miss rates. RESULTS: Six
      studies with a total of 465 patients could be included. The pooled miss rate for
      polyps of any size was 22% (95% CI: 19-26%; 370/1,650 polyps). Adenoma miss rate
      by size was, respectively, 2.1% (95% CI: 0.3-7.3%; 2/96 adenomas > or =10 mm),
      13% (95% CI: 8.0-18%; 16/124 adenomas 5-10 mm), and 26% (95% CI: 27-35%; 151/587
      adenomas 1-5 mm). Three studies reported data on nonadenomatous polyps: zero of
      eight nonadenomatous polyps > or =10 mm were missed (0%; 95% CI: 0-36.9%) and 83
      of 384 nonadenomatous polyps <10 mm were missed (22%; 95% CI: 18-26%).
      CONCLUSIONS: Colonoscopy rarely misses polyps > or =10 mm, but the miss rate
      increases significantly in smaller sized polyps. The available evidence is based
      on a small number of studies with heterogeneous study designs and inclusion
      criteria.

PMID- 16454842
TI  - A randomized crossover study of secretin-stimulated endoscopic and dreiling tube
      pancreatic function test methods in healthy subjects.
AB  - OBJECTIVES: We have developed an endoscopic method of secretin endoscopic
      pancreatic function testing (ePFT) to simplify duodenal fluid collection.
      Validation of the ePFT requires a direct comparison to the traditional PFT using
      a Dreiling tube (DT). Our aim was to compare bicarbonate concentrations [HCO3-]
      obtained by the ePFT and DT methods in healthy subjects (HS). METHODS: HS were
      randomized to either DT or ePFT, then crossed over to the other test after a
      minimum 1-wk washout. An age/weight-based sedation bolus was used for each test.
      DT protocol: Endoscopic placement of a DT was confirmed by fluoroscopy. After a
      baseline 15-min collection and administration of IV synthetic secretin, fluid was
      continuously collected in 15-min aliquots for an hour. ePFT protocol: Endoscopy
      was performed using a 6-mm endoscope. After gastric aspiration and discard and IV
      secretin, duodenal aspirates were obtained every 15-min for an hour. Fluid
      specimens were auto-analyzed for [HCO3-]. RESULTS: Twelve HS were enrolled (6F,
      mean age 37 yr). The difference in [HCO3-] between the two methods was not
      significant at the 0-, 30-, 45-, or 60-min collections. An excellent correlation
      in peak [HCO3-] was observed (R2 = 0.84, p < 0.001). Using a peak [HCO3-]
      cutpoint 80 mEq/L, there was 100% agreement between the methods; using cutpoint
      90 mEq/L, there was 83% agreement. CONCLUSIONS: The accuracy of the ePFT is
      similar to DT: There were minimal differences in [HCO3-] at each of the timed
      collections and at peak. There is an excellent correlation in peak [HCO3-] and
      high level of diagnostic agreement between the tests.

PMID- 16454843
TI  - Where have all the dreiling tubes gone?
AB  - The direct measurement of pancreatic function remains the best tool for
      diagnosing chronic pancreatitis, especially if imaging tests are normal or
      inconclusive. The most effective means of measuring pancreatic function is the
      standard hormone stimulation test using secretin. Traditionally, direct
      pancreatic function testing involves the fluoroscopic placement of an oroduodenal
      tube and collection of duodenal fluid containing pancreatic secretions after
      administration of a standardized dose of secretin and/or CCK. The test is time
      consuming and tedious to perform, and placement of the oroduodenal tube is often
      difficult for the person performing the test and uncomfortable for the patient.
      Bicarbonate concentration typically has been measured by back-titration,
      requiring specialized equipment no longer found in most hospital clinical
      chemistry laboratories. For these reasons, the direct testing of pancreatic
      function after secretin stimulation has become a much admired but rarely
      performed test, currently done in only a few centers in the United States. In
      this issue of the Journal, Stevens et al. report on a cross-over study of
      secretin-stimulated endoscopic pancreatic function test (ePFT) and dreiling tube
      pancreatic function test (D-PFT) in healthy subjects and demonstrate that the
      accuracy of the ePFT is comparable to that of the D-PFT (17). They have
      demonstrated the relative simplicity and reliability of ePFT, bringing it closer
      to the diagnostic armamentarium of the practicing physician. We may have lost the
      Dreiling tube but, in its place, gained a "gold standard" which will be more
      widely used.

PMID- 16454845
TI  - Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery.
AB  - OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is an increasingly prevalent
      problem. Treatment options are still under investigation. The primary aim of the
      study was to determine whether weight loss, achieved through Roux-en-Y gastric
      bypass (RYGBP), improved histopathology in obese patients with biopsy proven
      NASH. METHODS: One hundred and forty-nine patients were identified from a
      surgical database as having RYGBP for obesity and concomitant intra-operative
      liver biopsies from October 2001 to September 2003. Thirty-five patients were
      found to have evidence of NASH at the time of surgery. Nineteen patients were
      contacted and underwent repeat percutaneous liver biopsies. Biopsies were
      evaluated and compared in blinded fashion by an experienced hepatopathologist.
      Fasting lipid panel, insulin and glucose, hemoglobin A1c (HgbA1c), and liver
      enzymes were obtained. RESULTS: Significant differences were noted in the
      following variables pre- and post-bypass surgery: body mass index 46.8-28.8 kg/m2
      (p < 0.001); body weight in kilograms 132.1-79.7 (p < 0.001); glucose 102.9-94.1
      mg/dL (p = 0.015); Hgb A1c 5.79-5.15% (p = 0.026); high density lipoprotein 45.7
      64.4 mg/dL (p < 0.001); low density lipoprotein 112-88.6 mg/dL (p = 0.003);
      triglycerides 132.1-97 mg/dL (p = 0.013). Significant improvements in steatosis,
      lobular inflammation, portal, and lobular fibrosis were noted. Histopathologic
      criteria for NASH were no longer found in 17/19 patients (89%). CONCLUSIONS:
      Weight loss after gastric bypass surgery in obese patients with NASH results in
      significant improvement in glucose, HgbA1c. and lipid profiles. Furthermore,
      RYGBP results in significant improvement in the histological features of NASH
      with resolution of disease in a majority of these patients.

PMID- 16454844
TI  - Serum immune responses predict rapid disease progression among children with
      Crohn's disease: immune responses predict disease progression.
AB  - BACKGROUND AND AIM: Crohn's disease (CD) is a heterogeneous disorder
      characterized by diverse clinical phenotypes. Childhood-onset CD has been
      described as a more aggressive phenotype. Genetic and immune factors may
      influence disease phenotype and clinical course. We examined the association of
      immune responses to microbial antigens with disease behavior and prospectively
      determined the influence of immune reactivity on disease progression in pediatric
      CD patients. METHODS: Sera were collected from 196 pediatric CD cases and tested
      for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti
      CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using
      ELISA. Associations between immune responses and clinical phenotype were
      evaluated. RESULTS: Fifty-eight patients (28%) developed internal penetrating
      and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both
      anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease.
      The frequency of IP/S disease increased with increasing number of immune
      responses (p trend = 0.002). The odds of developing IP/S disease were highest in
      patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p =
      0.03). Pediatric CD patients positive for > or =1 immune response progressed to
      IP/S disease sooner after diagnosis as compared to those negative for all immune
      responses (p < 0.03). CONCLUSIONS: The presence and magnitude of immune responses
      to microbial antigens are significantly associated with more aggressive disease
      phenotypes among children with CD. This is the first study to prospectively
      demonstrate that the time to develop a disease complication in children is
      significantly faster in the presence of immune reactivity, thereby predicting
      disease progression to more aggressive disease phenotypes among pediatric CD
      patients.

PMID- 16454846
TI  - Role of home parenteral nutrition in chronic radiation enteritis.
AB  - OBJECTIVES: The management of chronic radiation enteritis (CRE) is difficult and
      often controversial. The aim of the study was to compare long-term outcome of
      patients with radiation-induced intestinal obstruction treated either surgically
      or with intestinal rest and home parenteral nutrition (HPN). METHODS: Thirty
      patients, with mechanical bowel obstruction due to CRE, were retrospectively
      included in the study and divided in two groups according to the first treatment
      approach. Seventeen patients underwent surgery (S group) and 13 patients were
      supported with HPN (HPN group). Survival, nutrition autonomy, number of
      surgeries, related complications and persistence of symptoms were evaluated in
      the two groups. Associations between factors and treatment group were assessed by
      means of the Wilcoxon rank sum test for continuous variables and the Fisher exact
      test for categorical variables. Overall survival was calculated using the Kaplan
      Meier method. RESULTS: The two groups were similar in terms of age, dose of
      radiation therapy, time of occurrence and degree of signs and symptoms. 7/13
      patients in the HPN group resolved the obstruction without surgery. 10/17
      patients of the S group developed intestinal failure which required HPN.
      Nutrition autonomy was achieved in 100% and 58.8% of HPN and S group respectively
      (p = 0.01). The overall five-year survival was 90.0% and 68.4% respectively in
      the HPN and S group (p = 0.0231). CONCLUSIONS: Both HPN and surgery are often
      necessary in patients with chronic radiation-induced intestinal obstruction.
      However, the long term nutrition autonomy and survival seem to be better in
      patients initially treated with intestinal rest and HPN.

PMID- 16454847
TI  - Does fecal occult blood testing really reduce mortality? A reanalysis of
      systematic review data.
AB  - INTRODUCTION: Colorectal cancer (CRC) is a common cause of cancer mortality. A
      variety of CRC screening strategies are being adopted in many developed
      countries. Fecal occult blood testing (FOBT) is one option for screening that has
      the most evidence for efficacy and is also the cheapest approach. Systematic
      reviews suggest that FOBT is effective in reducing CRC mortality but the data on
      overall mortality from any cause has rarely been synthesized. METHODS: Randomized
      controlled trials identified by a Cochrane review of the efficacy of FOBT were
      reanalyzed. Trials that reported on biennial FOBT with all cause mortality
      assessed at similar follow-up periods were analyzed. CRC, non-CRC, and all cause
      mortality were evaluated using a random effects model. RESULTS: Three trials were
      analyzed, involving 245,217 subjects with 2,148 CRC deaths after almost 3 million
      patient-years follow-up. The relative risk (RR) of CRC death in the FOBT arm was
      0.87 (95% CI = 0.8-0.95). The RR of non-CRC death in the FOBT group was 1.02 (95%
      CI = 1.00-1.04, p = 0.015). The increase in non-CRC in the FOBT group balanced
      the decrease in CRC mortality with no overall impact on mortality (RR of dying in
      the FOBT arm = 1.002, 95% CI = 0.989-1.015). CONCLUSION: The impact of FOBT in
      reducing mortality from any cause is uncertain and efficacy of this strategy for
      CRC screening needs reevaluation.

PMID- 16454848
TI  - Familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) is an autosomal-dominant colorectal cancer
      syndrome, caused by a germline mutation in the adenomatous polyposis coli (APC)
      gene, on chromosome 5q21. It is characterized by hundreds of adenomatous
      colorectal polyps, with an almost inevitable progression to colorectal cancer at
      an average age of 35 to 40 yr. Associated features include upper gastrointestinal
      tract polyps, congenital hypertrophy of the retinal pigment epithelium, desmoid
      tumors, and other extracolonic malignancies. Gardner syndrome is more of a
      historical subdivision of FAP, characterized by osteomas, dental anomalies,
      epidermal cysts, and soft tissue tumors. Other specified variants include Turcot
      syndrome (associated with central nervous system malignancies) and hereditary
      desmoid disease. Several genotype-phenotype correlations have been observed.
      Attenuated FAP is a phenotypically distinct entity, presenting with fewer than
      100 adenomas. Multiple colorectal adenomas can also be caused by mutations in the
      human MutY homologue (MYH) gene, in an autosomal recessive condition referred to
      as MYH associated polyposis (MAP). Endoscopic screening of FAP probands and
      relatives is advocated as early as the ages of 10-12 yr, with the objective of
      reducing the occurrence of colorectal cancer. Colectomy remains the optimal
      prophylactic treatment, while the choice of procedure (subtotal vs
      proctocolectomy) is still controversial. Along with identifying better
      chemopreventive agents, optimizing screening of extracolonic cancers and applying
      new radiological and endoscopic technology to the diagnosis and management of
      extracolonic features are the major challenges for the future.

PMID- 16454849
TI  - Thalidomide in the treatment of chronic hepatitis C unresponsive to alfa
      interferon and ribavirin.
AB  - Immunomodulation of thalidomide is represented by the antiinflammatory effect
      through inhibition of tumor necrosis factor alpha and costimulatory effect on
      human CD8+ T cells. We investigated the efficacy and safety of a 24-wk course of
      thalidomide at a dosage of 200 mg/day in eight patients with HCV chronic
      hepatitis nonresponders to interferon alpha plus ribavirin. We observed a
      significant mean decrease of serum aminotransferases and gamma
      glutamyltransferases of 39% and 61%, respectively (p = 0.017 and 0.02). Tumor
      necrosis factor-alpha in vitro production in mononuclear cells decreased with
      thalidomide in all the subjects (p = 0.028). Perforin- and granzyme-specific mRNA
      expression increased under thalidomide without statistical significance. A
      positive correlation between biochemical and immunological parameters was
      observed with higher increase of granzyme and perforin values in patients showing
      reduction of aminotransferases. Finally upregulation of T-helper 1 cytokine
      expression as mean interferon gamma/IL-10 ratio was evidenced. Thalidomide was
      well tolerated. In conclusion, thalidomide was able to reduce liver enzymes in
      six out of eight patients with chronic hepatitis C and to reduce tumor necrosis
      factor alpha production, representing a promising new approach for the treatment
      of HCV infection.

PMID- 16454851
TI  - Inherited thrombophilia and thrombosis in inflammatory bowel disease.

PMID- 16454852
TI  - Reanalysis of intragastric pH results based on updated correction factors for
      Slimline and Zinetics 24 single-use pH catheters.

PMID- 16454854
TI  - Eligibility criteria for antiviral therapy in HCV-positive patients: similar
      things to (almost) similar people.

PMID- 16454855
TI  - A tincture of time.

PMID- 16454856
TI  - The mystery of the esophagogastric junction is profoundly unraveled by omission
      of the term "cardia" from endoscopic reports.

PMID- 16454857
TI  - Quantitative genetics of larval life-history traits in Rana temporaria in
      different environmental conditions.
AB  - The degree to which genetic variation in a given trait varies among different
      populations of the same species and across different environments has seldom been
      quantified in wild vertebrate species. We investigated the expression of genetic
      variability and maternal effects in three larval life-history traits of the
      amphibian Rana temporaria. In a factorial laboratory experiment, five widely
      separated populations (max. 1600 km) were subjected to two different
      environmental treatments. Animal model analyses revealed that all traits were
      heritable (h(2) approximately 0.20) in all populations and under most treatment
      combinations. Although the cross-food treatment genetic correlations were close
      to unity, heritabilities under a restricted food regime tended to be lower than
      those under an ad libitum food regime. Likewise, maternal effects (m(2)
      approximately 0.05) were detected in most traits, and they tended to be most
      pronounced under restricted food conditions. We detected several cross
      temperature genetic and maternal effects correlations that were lower than unity,
      suggesting that genotype-environment interactions and maternal effect-environment
      interactions are a significant source of phenotypic variation. The results
      reinforce the perspective that although the expression of genetic and maternal
      effects may be relatively homogeneous across different populations of the same
      species, local variation in environmental conditions can lead to significant
      variation in phenotypic expression of quantitative traits through genotype
      environment and maternal effect-environment interactions.

PMID- 16454858
TI  - mus309 mutation, defective in DNA double-strand break repair, affects intergenic
      but not intragenic meiotic recombination in Drosophila melanogaster.
AB  - The effect was investigated of the hypomorphic DNA double-strand break repair,
      notably synthesis-dependent strand annealing, deficient mutation mus309 on the
      third chromosome of Drosophila melanogaster on intergenic and intragenic meiotic
      recombination in the X chromosome. The results showed that the mutation
      significantly increases the frequency of intergenic crossing over in two of three
      gene intervals of the X chromosome studied. Interestingly the increase was most
      prevalent in the tip of the X chromosome where crossovers normally are least
      frequent per physical map unit length. In particular crossing over interference
      was also affected, indicating that the effect of the mus309 mutation involves
      preconditions of crossing over but not the event of crossing over itself. On the
      other hand, the results also show that most probably the mutation does not have
      any effect on intragenic recombination, i.e. gene conversion. These results are
      fully consistent with the present molecular models of meiotic crossing over
      initiated by double-strand breaks of DNA followed by formation of a single-end
      invasion intermediate, or D-loop, which is subsequently processed to generate
      either crossover or non-crossover products involving formation of a double
      Holliday junction. In particular the results suggest that the mus309 gene is
      involved in resolution of the D-loop, thereby affecting the choice between double
      strand-break repair (DSBR) and synthesis-dependent strand annealing (SDSA)
      pathways of meiotic recombination.

PMID- 16454859
TI  - Clustering expressed genes on the basis of their association with a quantitative
      phenotype.
AB  - Cluster analyses of gene expression data are usually conducted based on their
      associations with the phenotype of a particular disease. Many disease traits have
      a clearly defined binary phenotype (presence or absence), so that genes can be
      clustered based on the differences of expression levels between the two
      contrasting phenotypic groups. For example, cluster analysis based on binary
      phenotype has been successfully used in tumour research. Some complex diseases
      have phenotypes that vary in a continuous manner and the method developed for a
      binary trait is not immediately applicable to a continuous trait. However,
      understanding the role of gene expression in these complex traits is of
      fundamental importance. Therefore, it is necessary to develop a new statistical
      method to cluster expressed genes based on their association with a quantitative
      trait phenotype. We developed a model-based clustering method to classify genes
      based on their association with a continuous phenotype. We used a linear model to
      describe the relationship between gene expression and the phenotypic value. The
      model effects of the linear model (linear regression coefficients) represent the
      strength of the association. We assumed that the model effects of each gene
      follow a mixture of several multivariate Gaussian distributions. Parameter
      estimation and cluster assignment were accomplished via an Expectation
      Maximization (EM) algorithm. The method was verified by analysing two simulated
      datasets, and further demonstrated using real data generated in a microarray
      experiment for the study of gene expression associated with Alzheimer's disease.

PMID- 16454860
TI  - An application of Bayesian QTL mapping to early development in double haploid
      lines of rainbow trout including environmental effects.
AB  - A Bayesian model and variable dimensional parameter estimation based on Markov
      chain Monte Carlo was applied to map quantitative trait loci (QTLs) in a doubled
      haploid mapping population of rainbow trout. To increase power, the analysis was
      performed using the multiple-QTL model, which simultaneously accounted for all
      the environmental and genetic main effects that influence the expression of early
      development life history traits. By doing so we obtained the posterior estimated
      effects for the environmental factors as well as the number, positions, and the
      effects for the QTLs. The analyses revealed QTLs for time at hatching, embryonic
      length and weight at swim-up stage. The posterior expectation of the number of
      QTLs in different linkage groups shows that at least four QTLs are needed to
      explain the observed differences in early development between the clonal lines.
      The Bayesian method effectively combined all the information available to
      accurately position these QTLs in the rainbow trout genome.

PMID- 16454861
TI  - Haplotype association analysis of human disease traits using genotype data of
      unrelated individuals.
AB  - Haplotype inference has become an important part of human genetic data analysis
      due to its functional and statistical advantages over the single-locus approach
      in linkage disequilibrium mapping. Different statistical methods have been
      proposed for detecting haplotype - disease associations using unphased multi
      locus genotype data, ranging from the early approach by the simple gene-counting
      method to the recent work using the generalized linear model. However, these
      methods are either confined to case - control design or unable to yield unbiased
      point and interval estimates of haplotype effects. Based on the popular logistic
      regression model, we present a new approach for haplotype association analysis of
      human disease traits. Using haplotype-based parameterization, our model infers
      the effects of specific haplotypes (point estimation) and constructs confidence
      interval for the risks of haplotypes (interval estimation). Based on the
      estimated parameters, the model calculates haplotype frequency conditional on the
      trait value for both discrete and continuous traits. Moreover, our model provides
      an overall significance level for the association between the disease trait and a
      group or all of the haplotypes. Featured by the direct maximization in haplotype
      estimation, our method also facilitates a computer simulation approach for
      correcting the significance level of individual haplotype to adjust for multiple
      testing. We show, by applying the model to an empirical data set, that our method
      based on the well-known logistic regression model is a useful tool for haplotype
      association analysis of human disease traits.

PMID- 16454864
TI  - Identification of ABC transporters in Sarcoptes scabiei.
AB  - We have identified and partially sequenced 8 ABC transporters from an EST dataset
      of Sarcoptes scabiei var. hominis, the causative agent of scabies. Analysis
      confirmed that most of the known ABC subfamilies are represented in the EST
      dataset including several members of the multidrug resistance protein subfamily
      (ABC-C). Although P-glycoprotein (ABC-B) sequences were not found in the EST
      dataset, a partial P-glycoprotein sequence was subsequently obtained using a
      degenerate PCR strategy and library screening. Thus a total of 9 potential S.
      scabiei ABC transporters representing the subfamilies A, B, C, E, F and H have
      been identified. Ivermectin is currently used in the treatment of hyper-infested
      (crusted) scabies, and has also been identified as a potentially effective
      acaricide for mass treatment programmes in scabies-endemic communities. The
      observation of clinical and in vitro ivermectin resistance in 2 crusted scabies
      patients who received multiple treatments has raised serious concerns regarding
      the sustainability of such programmes. One possible mechanism for ivermectin
      resistance is through ABC transporters such as P-glycoprotein. This work forms an
      important foundation for further studies to elucidate the potential role of ABC
      transporters in ivermectin resistance of S. scabiei.

PMID- 16454865
TI  - A new male-killing parasitism: Spiroplasma bacteria infect the ladybird beetle
      Anisosticta novemdecimpunctata (Coleoptera: Coccinellidae).
AB  - Whilst most animals invest equally in males and females when they reproduce, a
      variety of vertically transmitted parasites has evolved the ability to distort
      the offspring sex ratios of their hosts. One such group of parasites are male
      killing bacteria. Here we report the discovery of females of the ladybird
      Anisosticta novemdecimpunctata that produced highly female-biased offspring sex
      ratios associated with a 50% reduction in egg hatch rate. This trait was
      maternally transmitted with high efficiency, was antibiotic sensitive and was
      infectious following experimental haemolymph injection. We identified the cause
      as a male-killing Spiroplasma bacterium and phylogenetic analysis of rDNA
      revealed that it belongs to the Spiroplasma ixodetis clade in which other sex
      ratio distorters lie. We tested the potential for interspecific horizontal
      transfer by injection from an infected A. novemdecimpunctata line into uninfected
      individuals of the two-spot ladybird Adalia bipunctata. In this novel host, the
      bacterium was able to establish infection, transmit vertically and kill male
      embryos.

PMID- 16454866
TI  - Implications of increased susceptibility to predation for managing the sylvatic
      cycle of Echinococcus multilocularis.
AB  - The ability to increase the chances that infectious prey are taken by predators
      is an observed feature of many parasites that rely on one or more predator-prey
      relationships to complete their life-cycle. In the sylvatic life-cycle of
      Echinococcus multilocularis - the causative agent of human alveolar
      echinococcosis-- foxes are the final host, with voles acting as intermediate
      hosts. Here we review the evidence that E. multilocularis causes increased
      susceptibility to predation and present a general mathematical model for the
      sylvatic life-cycle. The ability to increase susceptibility to predation in the
      intermediate host reduces the sensitivity of the parasite population to adverse
      conditions. For example, there is no critical density of foxes below which the
      parasite is expected to die out, even if the effect of the parasite on infected
      prey is very small. We suggest that increased susceptibility to predation is a
      plausible explanation for the observed resilience of E. multilocularis during and
      following field trials of praziquantel baiting.

PMID- 16454867
TI  - Immunostaining of spores and plasmodia of disparate myxozoan genera with comments
      on the properties of the sporular mucus envelope.
AB  - Species of the phylum Myxozoa are common parasites of fish and can cause severe
      losses in cultured species. Although a number of myxozoan life-cycles have now
      been elucidated, little is known about the biology of these organisms in the fish
      host. Monoclonal antibody B4 raised to the myxozoan Tetracapsuloides bryosalmonae
      has been previously noted to react with a number of species infecting fish
      kidney. We present the results of a survey of 55 myxosporean species that
      determined that this antibody detects an antigen on the spore surface of 33 of
      these species in the genera Myxobolus, Sphaerospora and Thelohanellus. However,
      there appears to be no clear relationship between those spores that contain the
      MAb B4 reactive antigen and the host or organ in which they are detected. The
      antigen appears to be synthesized in the plasmodial cytoplasm and is intimately
      associated with the surface of the spore capsules and, where present, the mucus
      envelope. The nature of this envelope is further discussed in relation to its
      formation and distinctive properties.

PMID- 16454868
TI  - Paraphilic behaviours in a parkinsonian patient with hedonistic homeostatic
      dysregulation.

PMID- 16454871
TI  - Is interventional closure the current treatment of choice for selected patients
      with deficient atrial septation?

PMID- 16454872
TI  - The mystery of nuchal translucency.

PMID- 16454873
TI  - The "wall-to-wall" heart in the patient with pulmonary atresia and intact
      ventricular septum.

PMID- 16454874
TI  - The spectrum of congenital cardiac malformations encountered in six children with
      Kabuki syndrome.
AB  - We investigated the prevalence and forms of congenital cardiac malformations in
      six children with Kabuki syndrome. There were three girls and three boys,
      diagnosed at a median age of 1.7 years, with a range from 0.7 to 11.1 years.
      Cardiac lesions were present in five children (83%), specifically complete
      transposition, tetralogy of Fallot, coarctation of the aorta, ventricular septal
      defect, and patency of the arterial duct. Characteristic dysmorphic findings were
      noted in all patients, as well as a strong predisposition to severe problems with
      feeding in the neonatal period, and developmental delay. Cardiologists should be
      alert to this syndrome in children who present with the aforementioned
      constellation of findings, as patients with mild expression of Kabuki syndrome
      may go unrecognized for a considerable time.

PMID- 16454875
TI  - Live three-dimensional paediatric intraoperative epicardial echocardiography as a
      guide to surgical repair of atrioventricular valves.
AB  - Real-time three dimensional echocardiography is increasingly used for imaging
      patients with congenital cardiac malformations. One of the limitations of a
      transthoracic approach is that intervening structures can impact on the quality
      of the images obtained. We hypothesised that, during surgery, epicardial three
      dimensional echocardiography would provide images of high quality. We report our
      findings in eight children or young adults, with weights ranging from 2.8 to 70
      kilograms, in whom we used this approach. In all cases, we obtained images of
      good quality, which could be analysed rapidly in the operating room. Of the eight
      cases, seven had echocardiographic findings which matched exactly the surgical
      findings. The remaining child had been diagnosed echocardiographically with a
      cleft in the aortic leaflet of the mitral valve, but was found at surgery to have
      a double orifice in the valve.

PMID- 16454876
TI  - Exercise performance in children and adolescents after the Ross procedure.
AB  - OBJECTIVES: The Ross procedure is increasingly utilized in the treatment of
      aortic valvar disease in children and adolescents. Our purpose was to compare pre
      and post-operative exercise state in this population. METHODS: We included
      patients who underwent the Ross procedure at our institution between January,
      1995, and December, 2003, and in whom we had performed pre- and post-operative
      exercise stress tests. We used a ramp bicycle protocol to measure consumption of
      oxygen and production of carbon dioxide. Cardiac output was estimated from
      effective pulmonary blood flow by the helium acetylene re-breathing technique.
      RESULTS: We studied 26 patients, having a median age at surgery of 15.7 years,
      with a range from 7.5 to 24.1 years. The primary indication for surgery in two
      thirds was combined aortic stenosis and insufficiency. Median time from the
      operation to the post-operative exercise stress test was 17.4 months, with a
      range from 6.7 to 30.2 months. There was a trend toward lower maximal consumption
      of oxygen after the procedure, at 36.3 plus or minus 7.6 millilitres per kilogram
      per minute (83.9% predicted) as opposed to 38.6 plus or minus 8.4 millilitres per
      kilogram per minute (88.5% predicted, p equal to 0.06). Patients after the
      procedure, however, had significantly increased adiposity, so that there was no
      difference in maximal consumption of oxygen indexed to ideal body weight before
      and after the operation. In 20 of the patients, aerobic capacity improved or was
      stable after the operation. There was no post-operative chronotropic impairment.
      CONCLUSIONS: In the majority of patients following the Ross procedure, exercise
      performance is stable and within the normal range of a healthy age and sex
      matched population, despite sedentary lifestyles and increased adiposity.

PMID- 16454877
TI  - Quantitative analysis of procalcitonin after pediatric cardiothoracic surgery.
AB  - Procalcitonin appears to be an early and sensitive marker of bacterial infection
      in a variety of clinical settings. The use of levels of procalcitonin to predict
      infection in children undergoing cardiac surgery, however, may be complicated by
      the systemic inflammatory response that normally accompanies cardiopulmonary
      bypass. The aim of our study was to estimate peri-operative concentrations of
      procalcitonin in non-infected children undergoing cardiac surgery. Samples of
      serum for assay of procalcitonin were obtained in 53 patients at baseline, 24,
      48, and 72 hours following cardiac surgery. Concentrations were assessed using an
      immunoluminetric technique. Median concentrations were lowest at baseline at less
      than 0.5 nanograms per millilitre, increased at 24 hours to 1.8 nanograms per
      millilitre, maximized at 48 hours at 2.1 nanograms per millilitre, and decreased
      at 72 hours to 1.3 nanograms per millilitre, but did not return to baseline
      levels. Ratios of concentrations between 24, 48 and 72 hours after surgery as
      compared to baseline were 6.15, with 95 percent confidence intervals between 4.60
      and 8.23, 6.49, with 95 percent confidence intervals from 4.55 to 9.27, and 4.26,
      with 95 percent confidence intervals between 2.78 and 6.51, respectively, with a
      p value less than 0.001. In 8 patients, who had no evidence of infection,
      concentrations during the period from 24 to 72 hours were well above the median
      for the group. We conclude that concentrations of procalcitonin in the serum
      increase significantly in children following cardiac surgery, with a peak at 48
      hours, and do not return to baseline within 72 hours of surgery. A proportion of
      patients, in the absence of infection, had exaggerated elevations post
      operatively.

PMID- 16454878
TI  - Can we do without routine fenestration in extracardiac total cavopulmonary
      connections? Report on 84 consecutive patients.
AB  - Fenestration is still widely used in right heart bypass operations. Our study was
      conducted to assess its need in the most recent modification, the completion of a
      total cavopulmonary connection with an extracardiac tube. The extracardiac
      approach was introduced at our institution in January, 1999. Since June of 2000,
      no patient had a fenestration. If more than 1 risk factor amongst ventricular
      function being more than moderately impaired, atrioventricular valvar
      regurgitation more than moderate, mean pulmonary arterial pressure more than 15
      millimetres of mercury, mean atrial pressure higher than 12 millimetres of
      mercury, pulmonary arterial distortion, or other than sinus rhythm was present
      preoperatively, the patient was considered a "high risk" candidate.
      Postoperatively elevated pulmonary arterial pressure higher than 16 millimetres
      of mercury, prolonged effusions and requirement for drainage longer than 7 days,
      and death were considered endpoints in the statistical analysis. Our study group
      included 84 patients who underwent surgery up to August, 2004. A previous
      bidirectional cavopulmonary anastomosis had been accomplished in 73 patients at a
      mean age of 27.01 plus or minus 32.60 months, with a median of 11.5 months,
      without creating an additional source of flow of blood to the lungs. At the time
      of the total cavopulmonary connection, the mean age was 66.4 plus or minus 60.1
      months, with a median of 37.1 months, and a range from 17.3 to 251.2 months, with
      50 patients being younger than 48 months. We deemed 16 patients to be at "high
      risk". These patients were older at the time of bidirectional cavopulmonary
      anstomosis (p smaller than 0.016), at the time of completion (p smaller than
      0.019), and also differed in size at time of completion (p smaller than 0.020).
      They required a longer time on cardiopulmonary bypass (p smaller than 0.015), and
      reached higher early postoperative pulmonary arterial pressures after completion
      (p smaller than 0.025). There were no differences between groups of patients
      having up to 1 or more risk factors in regard to need for intubation (p smaller
      than 0.511), pulmonary arterial pressures after extubation (p smaller than
      0.817), and duration of chest drainage (p smaller than 0.650). Three patients
      died, one in the group deemed at high risk. There was no death in the last 38
      patients. We conclude that a total cavopulmonary connection with an extracardiac
      tube can be performed without fenestration, even if the patients are deemed to be
      at increased risk. Early staging of patients with functionally univentricular
      physiology might be one of the keys for these findings.

PMID- 16454879
TI  - Athlete's heart in prepubertal male swimmers.
AB  - To determine the cardiac response to intensive endurance training during
      prepuberty, we studied 22 male prebubertal swimmers who had been trained for at
      least 3 years, with a mean of 3.91 years and a standard deviation of 1.10 years,
      and 8 hours per week, the mean being 10.0 hours and the standard deviation 1.7
      hours. The control group consisted of 21 boys of similar age, height and weight
      (p is more than 0.05 for all), who were not participating regularly in sporting
      activities. Left ventricular dimensions and systolic function were examined with
      M-Mode; velocities and durations of transmitral flow were measured with pulsed
      wave Doppler; and tissue Doppler velocities and durations were measured with
      pulsed wave tissue Doppler echocardiography. We determined the regional
      velocities of the lateral mitral annulus in four-chamber position, the left
      ventricular posterolateral wall, and the midseptum in long-axis position.
      Interventricular septal thickness, left ventricular posterior wall thickness,
      left ventricular mass and relative wall thickness were increased in swimmers (p
      is less than 0.05). All the tissue Doppler measurements were similar in both
      groups, except the septal isovolumic relaxation time. We observed that the left
      ventricular wall thickness had increased concentrically in prepubertal swimmers
      compared to controls, without a significant change in the left ventricular
      diastolic diameter. This finding is contrary to the previous studies on adult
      swimmers. Whether the structural changes observed in our study reflect the unique
      cardiac adaptation of the hearts of children to exercise will only be disclosed
      by longitudinal studies of prepubertal athletes.

PMID- 16454880
TI  - The impact of the severity of disease and social disadvantage on quality of life
      in families with congenital cardiac disease.
AB  - OBJECTIVE: Increasing rates of survival have raised the question of medical and
      psychosocial factors contributing to quality of life of patients with congenital
      cardiac disease. We investigated the impact of the severity of disease, and
      social disadvantage, on the quality of life of patients and their primary
      caregivers. METHODS: One hundred and thirty two families participated in a
      computer-assisted evaluation of their quality of life in a German outpatient
      centre for paediatric cardiac diseases. Quality of life for the patients was
      evaluated by a multi-dimensional proxy-measure. The quality of life of the
      caregivers was evaluated by a multi-dimensional self-reporting measure. Severity
      of the disease was evaluated by the responsible paediatrician. Social
      disadvantage was defined as single-parent status, ethnic minority status,
      unfinished parental education or professional training, and/or unemployment.
      Analyses of variance were calculated with mild, moderate, or severe forms of
      disease, and risk as opposed to no risk for social status, both factors being
      treated independently, and the quality of life of the patients and their
      caregivers as dependent variables. RESULTS: We demonstrated significant effects
      of the severity of disease on the quality of life of the children, and of social
      disadvantage on the quality of life of both the children and their parents. A
      significant interactive effect indicated a cumulative negative impact of the
      severity of the disease and social disadvantage on the quality of life of the
      patients. CONCLUSION: Programmes providing psychosocial support for children with
      cardiac disease and their caregivers should consider risk factors which are both
      medical and social.

PMID- 16454881
TI  - Extreme levels of alpha-fetoprotein in a newborn with a benign intrapericardial
      teratoma.
AB  - We report a neonate presenting with an intrapericardial benign teratoma and an
      exceptionally high level of alpha-fetoprotein. Such severe elevation of alpha
      fetoprotein in a neonate with a teratoma is usually associated with the presence
      of immature or malignant elements, compromising the prognosis. The tumour in our
      patient, however, proved to be completely benign. We discuss recent findings with
      regard to normal levels of alpha-fetoprotein levels in preterm infants, and in
      children with neonatal teratomas.

PMID- 16454882
TI  - An infant with hypoplastic left heart syndrome and spinal muscular atrophy.
AB  - We report an infant with hypoplastic left heart syndrome consisting of mitral
      valvar atresia, aortic valvar atresia, hypoplasia of the aortic arch and
      coarctation of the aorta, who demonstrated respiratory failure and global
      hypotonia, and who was eventually diagnosed with spinal muscular atrophy.

PMID- 16454883
TI  - Post-mortem magnetic resonance imaging provides the diagnosis following aortic
      rupture in an infant with treated aortic interruption.
AB  - In the United Kingdom, there has been a steady decline in the number of
      conventional autopsies performed in children. For cardiovascular disease,
      structural and not pathological considerations are often more important in
      defining the cause of death. Magnetic resonance imaging is now often used in the
      assessment of congenital cardiac malformations during life. In this case report,
      we demonstrate how post-mortem magnetic resonance imaging was able to establish
      the diagnosis of aortic rupture in a patient who had undergone surgical repair of
      aortic interruption. In this patient, the parents had declined conventional
      histopathological autopsy, but were happy to consent to magnetic resonance post
      mortem assessment.

PMID- 16454884
TI  - Intravenous sildenafil as an effective treatment of pulmonary hypertensive crises
      during acute intestinal malabsorption.
AB  - Oral sildenafil has been demonstrated to be an effective treatment for pulmonary
      hypertension, and is increasingly used in children. We report an infant with
      pulmonary hypertension, stable on regular treatment with oral sildenafil, who
      presented in acute respiratory failure after aspiration, requiring ventilation
      and intensive care. The course of the stay in intensive care was difficult, with
      recurrent pulmonary hypertensive crises despite use of oral sildenafil, use of
      100% oxygen, high frequency oscillatory ventilation, and inhaled nitric oxide. In
      view of his instability, and the presumed inability to absorb the sildenafil
      orally due to gastrointestinal malabsorption, sildenafil was administered as a
      continuous intravenous infusion. With this therapy, it proved possible to wean
      from oxygen, nitric oxide, and ventilatory support. Intravenous sildenafil,
      therefore, might be an effective alternative for children with pulmonary
      hypertension during episodes of acute deterioration and malabsorption, preventing
      life-threatening pulmonary hypertensive crises. Its pharmacokinetics, efficacy,
      and safety, nonetheless, need to be validated in randomized controlled trials.

PMID- 16454885
TI  - Iatrogenic thrombosis on the tendinous cords of the tricuspid valve.
AB  - Iatrogenic thrombosis within the heart is rare following intracardiac operations.
      We undertook surgery to correct a 30-month-old girl with Fallot's tetralogy.
      After a period of 6 months following the operation, echocardiography revealed a
      thrombus measuring 16 by 12 millimetres attached to the tendinous cords
      supporting the antero-superior leaflet of the tricuspid valve. Medical treatment
      having failed, we proceeded to surgical excision so as to avoid pulmonary
      embolisation. Histological examination confirmed the thrombotic nature of the
      mass.

PMID- 16454886
TI  - Severe stenosis of a long tracheal segment, with agenesis of the right lung and
      left pulmonary arterial sling.
AB  - A baby presented at term with respiratory distress was managed with
      extracorporeal membrane oxygenation. Bronchoscopy revealed tracheal hypoplasia,
      complete tracheal rings, and agenesis of the right main bronchus.
      Echocardiography showed a left pulmonary arterial sling arising from the proximal
      part of the right pulmonary artery. Cardiac catheterization demonstrated abnormal
      pulmonary vasculature in the left lung which would have prevented survival, even
      after surgical repair. Diagnostic catheterization was important in delineating
      the anatomy, and aided in the decision not to proceed with surgical repair.

PMID- 16454887
TI  - Atrioventricular septal defect with intact septal structures presenting as left
      atrioventricular valvar insufficiency.
AB  - We describe the findings in a six-year-old girl who presented with signs of left
      atrioventricular valvar insufficiency. The echocardiogram showed a common
      atrioventricular junction, intact atrial and ventricular septal structures. At
      surgery, the left-sided atrioventricular valve was found to be tri-foliate, and
      corrected by valvoplasty. To the best of our knowledge, this is the first case of
      atrioventricular septal defect with common atrioventricular junction and intact
      septal structures diagnosed during life.

PMID- 16454888
TI  - Cantrell's syndrome.

PMID- 16454889
TI  - Radiofrequency catheter ablation of symptomatic neonatal rhabdomyoma.

PMID- 16454893
TI  - The application of genomic technology to combat parasitic disease.

PMID- 16454894
TI  - An historical and genomic view of schistosome conjugal biology with emphasis on
      sex-specific gene expression.
AB  - The genetic programmes associated with the sexual biology of dioecious
      schistosomes remain a critically important but significantly understudied area of
      parasitology. Throughout the last four decades, progress has been slow in
      describing the gross antigenic and proteomic differences linked to sexually
      mature schistosomes and in characterizing some of the sex-associated transcripts
      and regulatory mechanisms induced during developmental maturation. These
      investigations have been severely hindered by the lack of complete EST/genomic
      information, as well as corresponding post- and functional-genomic tools for
      studying these pathogenic parasites. As near complete transcriptomes for
      Schistosoma japonicum and S. mansoni have recently been reported, and both DNA
      microarrays and post-transcriptional gene silencing have been applied to
      schistosomes, the tools and techniques for the high-throughput identification and
      characterization of transcripts involved in conjugal biology are now readily
      available. Here, an historical review is presented that summarizes some of the
      most significant findings associated with schistosome sex and sexual maturation
      during the last several decades. Following this discussion is a current overview
      of some modern day genomic approaches used to study schistosomes, which
      illustrates how major advances in the field of conjugal biology will be achieved.

PMID- 16454895
TI  - Data mining parasite genomes.
AB  - The term 'data mining' can be used to describe any process where useful
      information is extracted from data with a large background of 'noise'. In the
      context of a genome project, several stages involve data mining. Amongst the
      sequence data, 'signals' need to be detected that indicate the presence of
      interesting features. Often this involves differentiating between transcribed and
      non-transcribed bases to predict coding regions. After detection, defining the
      roles of these sequences involves sifting through multiple lines of evidence. If
      these roles are accurately reflected in genome annotation, they can be used by
      researchers to frame queries and interrogate the data further.

PMID- 16454896
TI  - Probing Trypanosoma cruzi biology with DNA microarrays.
AB  - The application of genome-scale approaches to study Trypanosoma cruzi-host
      interactions at different stages of the infective process is becoming possible
      with sequencing and assembly of the T. cruzi genome nearing completion and
      sequence information available for both human and mouse genomes. Investigators
      have recently begun to exploit DNA microarray technology to analyze host
      transcriptional responses to T. cruzi infection and dissect developmental
      processes in the complex T. cruzi life-cycle. Collectively, information generated
      from these and future studies will provide valuable insights into the molecular
      requirements for establishment of T. cruzi infection in the host and highlight
      the molecular events coinciding with disease progression. While the field is in
      its infancy, the availability of genomic information and increased accessibility
      to relatively high-throughput technologies represents a significant advancement
      toward identification of novel drug targets and vaccine candidates for the
      treatment and prevention of Chagas' disease.

PMID- 16454897
TI  - Integrating genetics and genomics to identify new leads for the control of
      Eimeria spp.
AB  - Eimerian parasites display a biologically interesting range of phenotypic
      variation. In addition to a wide spectrum of drug-resistance phenotypes that are
      expressed similarly by many other parasites, the Eimeria spp. present some unique
      phenotypes. For example, unique lines of Eimeria spp. include those selected for
      growth in the chorioallantoic membrane of the embryonating hens egg or for faster
      growth (precocious development) in the mature host. The many laboratory-derived
      egg-adapted or precocious lines also share a phenotype of a marked attenuation of
      virulence, the basis of which is different as a consequence of the in ovo or in
      vivo selection procedures used. Of current interest is the fact that some wild
      type populations of Eimeria maxima are characterized by an ability to induce
      protective immunity that is strain-specific. The molecular basis of phenotypes
      that define Eimeria spp. is now increasingly amenable to investigation, both
      through technical improvements in genetic linkage studies and the availability of
      a comprehensive genome sequence for the caecal parasite E. tenella. The most
      exciting phenotype in the context of vaccination and the development of new
      vaccines is the trait of strain-specific immunity associated with E. maxima.
      Recent work in this laboratory has shown that infection of two inbred lines of
      White Leghorn chickens with the W strain of E. maxima leads to complete
      protection to challenge with the homologous parasite, but to complete escape of
      the heterologous H strain, i.e. the W strain induces an exquisitely strain
      specific protective immune response with respect to the H strain. This dichotomy
      of survival in the face of immune-mediated killing has been examined further and,
      notably, mating between a drug-resistant W strain and a drug-sensitive H strain
      leads to recombination between the genetic loci responsible for the specificity
      of protective immunity and resistance to the anticoccidial drug robenidine. Such
      a finding opens the way forward for genetic mapping of the loci responsible for
      the induction of protective immunity and integration with the genome sequencing
      efforts.

PMID- 16454898
TI  - The application of mass spectrometry to identify immunogenic components of
      excretory/secretory products from adult Dictyocaulus viviparus.
AB  - Proteomics has come to the forefront in the post-genomic era. The ability to
      compare and identify proteins expressed in a particular cell type under specific
      physiological or pathological states requires a range of technologies, including
      separation of complex protein or peptide mixtures, densitometry-based or isotope
      coded methods for comparison of multiple proteomes, and mass spectrometric
      methods for identification of individual low abundance proteins. Although an
      emergent technology, thus far, proteomics has provided new perspectives on many
      problems in biomedical science. In parasitology, proteomics has been used to
      answer specific biological questions relating to survival and development, and
      also to identify candidates for vaccines. Here, we describe an ongoing research
      programme in which proteomics is being used to identify potential vaccine
      candidates for the bovine lungworm, Dictyocaulus viviparus. This work is focusing
      on antibody responses to the adult parasite excretory/secretory (ES) products,
      with selection of candidate antigens based on differential screening with serum
      from immune versus non-immune animals to simplify the proteome and the ensuing
      analytical challenges. Thus far, we have identified seven candidate proteins
      using this strategy. Of these, one protein showed significant identity to a
      previously cloned gene from D. viviparus, whilst the other six proteins have
      shown no significant identities. Isolation of further peptide sequences is now
      warranted to facilitate cloning of the genes encoding these antigens.

PMID- 16454899
TI  - The use of Caenorhabditis elegans in parasitic nematode research.
AB  - There is increasing interest in the use of the free-living nematode
      Caenorhabditis elegans as a tool for parasitic nematode research and there are
      now a number of compelling examples of its successful application. C. elegans has
      the potential to become a standard tool for molecular helminthology researchers,
      just as yeast is routinely used by molecular biologists to study vertebrate
      biology. However, in order to exploit C. elegans in a meaningful manner, we need
      a detailed understanding of the extent to which different aspects of C. elegans
      biology have been conserved with particular groups of parasitic nematodes. This
      review first considers the current state of knowledge regarding the conservation
      of genome organisation across the nematode phylum and then discusses some recent
      evolutionary development studies in free-living nematodes. The aim is to provide
      some important concepts that are relevant to the extrapolation of information
      from C. elegans to parasitic nematodes and also to the interpretation of
      experiments that use C. elegans as a surrogate expression system. In general,
      examples have been specifically chosen because they highlight the importance of
      careful experimentation and interpretation of data. Consequently, the focus is on
      the differences that have been found between nematode species rather than the
      similarities. Finally, there is a detailed discussion of the current status of C.
      elegans as a heterologous expression system to study parasite gene function and
      regulation using successful examples from the literature.

PMID- 16454900
TI  - Screening and synthesis: high throughput technologies applied to parasitology.
AB  - High throughput technologies continue to develop in response to the challenges
      set by the genome projects. This article discusses how the techniques of both
      high throughput screening (HTS) and synthesis can influence research in
      parasitology. Examples of the use of targeted and phenotype-based HTS using
      unbiased compound collections are provided. The important issue of identifying
      the protein target(s) of bioactive compounds is discussed from the synthetic
      chemist's perspective. This article concludes by reviewing recent examples of
      successful target identification studies in parasitology.

PMID- 16454901
TI  - Raman and infrared microspectral imaging of mitotic cells.
AB  - We report the first ever Raman and infrared microspectroscopic images of human
      cells at different stages of mitosis. These spectroscopic methods monitor the
      distribution of condensed nuclear chromatin, and other biochemical components,
      utilizing inherent protein and DNA spectral markers, and, therefore, do not
      require the use of any stains. In conjunction with previously reported data from
      the G1, S, and G2 phases of the cell cycle, the complete cell division cycle has
      now been mapped by spectroscopic methods. Although the results reported here do
      not offer new insights into the distribution of biochemical components during
      mitosis, the recognition of cell division without the use of stains, and the
      possibility of doing so on living cells, may be useful for an automatic,
      spectroscopic determination of the proliferation rates of cells and tissues.
      Spectral images were constructed by plotting spectral intensities of DNA or
      protein versus the coordinates from which spectra were recorded. We found that
      both Raman and infrared intensities depend on the overall chromatin density
      variation among the individual subphases of mitosis.

PMID- 16454902
TI  - Prediction of oil and oleic acid concentrations in individual corn (Zea mays L.)
      kernels using near-infrared reflectance hyperspectral imaging and multivariate
      analysis.
AB  - Due to their heterogeneous structure and variability in form, individual corn
      (Zea mays L.) kernels present an optical challenge for nondestructive
      spectroscopic determination of their chemical composition. Increasing demand in
      agricultural science for knowledge of specific traits in kernels is driving the
      need to find high-throughput methods of examination. In this study macroscopic
      near-infrared (NIR) reflectance hyperspectral imaging was used to measure small
      sets of kernels in the spectroscopic range of 950 nm to 1700 nm. Image analysis
      and principal component analysis (PCA) were used to determine kernel germ from
      endosperm regions as well as to define individual kernels as objects out of sets
      of kernels. Partial least squares (PLS) analysis was used to predict oil or oleic
      acid concentrations derived from germ or full kernel spectra. The relative
      precision of the minimum cross-validated root mean square error (RMSECV) and root
      mean square error of prediction (RMSEP) for oil and oleic acid concentration were
      compared for two sets of two hundred kernels. An optimal statistical prediction
      method was determined using a limited set of wavelengths selected by a genetic
      algorithm. Given these parameters, oil content was predicted with an RMSEP of
      0.7% and oleic acid content with an RMSEP of 14% for a given corn kernel.

PMID- 16454905
TI  - Evaluation of pretreatment strategies for near-infrared spectroscopy calibration
      development of unground and ground compound feedingstuffs.
AB  - Chemometric procedures are usually applied to near-infrared (NIR) spectra in
      order to obtain prediction models. These procedures include the application of
      different combinations of spectral mathematical pretreatments for the improvement
      of calibrations and the selection of the best model on the basis of validation
      results. In this work, we used an automatic routine to obtain calibrations for
      unground and ground compound feedingstuffs (N=354 samples), including 49
      combinations of pretreatments (first and second derivatives, an auto scaling
      procedure, detrending and two versions of multiplicative scatter correction).
      Calibrations for crude fiber and crude protein were developed without elimination
      of outliers and with 2 or 9 maximum passes of elimination of outliers. Validation
      statistics were highly influenced by the pretreatments used, as a combined result
      of their ability to improve the detection of outliers and the model adjustment.
      The standard error of prediction (SEP) values ranged from 0.61 to 1.27 for crude
      protein (CP) and from 0.74 to 1.33 for crude fiber (CF). In spite of the fact
      that validation statistics did not show a clear distribution pattern, some
      combinations of pretreatments provided consistently better results.

PMID- 16454907
TI  - Regional difference of water content in human skin studied by diffuse-reflectance
      near-infrared spectroscopy: consideration of measurement depth.
AB  - Diffuse reflectance (DF) spectra in the 1250-2500 nm region were measured in vivo
      for the skin of the forehead, cheek, jaw, elbow, volar forearm, palm, knee, and
      heel of seven healthy volunteers, using a Fourier transform near-infrared (FT
      NIR) spectrophotometer with a fiber-optic probe. Apparent regional differences of
      water content in the skin, as estimated from the diffuse reflectance NIR spectra,
      are discussed in relation to the influence of measurement depth. The NIR spectra
      were collected with or without a 300 microm gap between the fiber-optic probe and
      the skin surface. For comparison, in vitro NIR spectra of stratum corneum sheets
      equilibrated at 41, 50, 63, and 81% relative humidity, at 25 degrees C, were also
      obtained. There was a difference in the ratio of the two water bands centered
      near 1450 nm and 1900 nm between the contact and non-contact measurements. In
      addition, regional differences of water content calculated from the peak height
      of the 1900 nm water band, which was normalized to the peak height of the 2175 nm
      amide band, were compared. The results of Monte Carlo simulation indicated that
      the apparent regional differences arise at least in part from differences in the
      measurement depth due to differences in specular reflection at the skin surface
      and in the thickness of the stratum corneum.

PMID- 16454908
TI  - Application of micro-attenuated total reflectance infrared spectroscopy to
      quantitative analysis of optical fiber coatings: effects of optical contact.
AB  - Micro-attenuated total reflectance (ATR) infrared spectroscopy is one of the few
      methods applicable for an in situ analysis of polymer coatings. In this method,
      the information is collected using an internal reflection element (IRE), which is
      brought into contact with the coated substrate. Perfect optical contact is hardly
      achievable for non-flat substrates and/or for those samples that cannot be well
      aligned with respect to the IRE. Consequently, the infrared peak intensities,
      their ratios, and all quantities calculated from the spectra become dependent
      upon the optical contact quality. In this work, we suggest a model that describes
      the peak intensities in terms of the optical contact. As an illustration, we
      apply this model to polymer-coated optical fibers. Relatively small diameters of
      tested fibers and their cylindrical shape result in imperfect optical contact
      between the sample and the IRE. Spectroscopic approaches of determining the
      degree of cure of polymer coatings are analyzed in view of the obtained results.
      Ways of minimizing the error induced by imperfect optical contact are suggested.

PMID- 16454909
TI  - Preliminary evaluation of micro-Raman spectrometry for the characterization of
      individual aerosol particles.
AB  - Raman spectrometry has been used to determine the graphitic C content and to
      estimate particle size and disordered character of the C in aerosol particulate
      matter collected on filters, with sample spot sizes on the order of 100 microm
      being analyzed. Individual analysis of particulate matter with aerodynamic
      diameters less than 10 microm has therefore not been considered. In this
      investigation, various size fractions of aerosol particulate matter originating
      from both indoor and outdoor sources were collected by means of impactors or
      passive dry deposition on different types of substrate and analyzed by means of
      micro-Raman spectrometry with spot sizes ranging from 1-5 microm. The aim was to
      investigate the possible application of micro-Raman spectrometry to the molecular
      characterization of individual aerosol particles and to assess the applicability
      of the various substrates in such an analysis. It was demonstrated that the
      molecular characterization of most inorganic particles is trivial, but organic
      and heterogeneous conglomerates proved to be more challenging. Spectral
      contributions of the substrates, currently favored for individual particle
      analysis, were significant. Results obtained from micro Raman spectrometry can
      certainly add valuable molecular information on individual aerosol particles as
      small as 1 microm aerodynamic diameter.

PMID- 16454910
TI  - Surface-enhanced Raman spectroscopy of chernozem humic acid and their fractions
      obtained by coupled size exclusion chromatography-polyacrylamide gel
      electrophoresis (SEC-PAGE).
AB  - A humic acid extracted from a chernozem soil was fractionated combining size
      exclusion chromatography and polyacrylamide electrophoresis (SEC-PAGE). Three
      fractions named A, B, and C+D, with different electrophoretic mobilities and
      molecular sizes (MS), were obtained and subsequently characterized by
      thermochemolysis and surface-enhanced Raman spectroscopy (SERS). The data
      confirmed that fraction A, with the higher MS, was more aliphatic than fractions
      B and C+D and, in turn, fractions with lower MS (B and C+D) denoted an enrichment
      in lignin residues. These structural features explain conformational changes when
      varying the pH in the humic fraction A and indicated that combination of the two
      techniques is a good approach for characterizing humic substances.

PMID- 16454911
TI  - Doppler width limited near-infrared Raman spectrometer.
AB  - A new ultra high resolution spontaneous Raman spectrometer with a single mode
      tunable laser diode as an excitation source and a 0.275 m, f/#4 spectrograph is
      presented. The spectrometer is expanded by an atomic vapor (Rb) absorption
      filter. One of the rubidium resonance lines serves as the frequency marker by
      absorbing selected Raman lines during the frequency scan of the excitation laser.
      High resolution was achieved while preserving the speed of the spectrometer. The
      extended spectrometer's capability was tested by differentiating overlapping
      Raman lines from molecular hydrogen isotopomers: H2, D2, and HD. Experiments were
      carried out at 300 K and pressures near 10(4) Pa. Spectral lines separated by
      approximately 10 Ghz (0.3 cm-1) can be resolved with this instrument with data
      collection times of minutes.

PMID- 16454912
TI  - Improved monochromatic imaging spectrometer.
AB  - Distortion inherent to a previously described system for acquisition of two
      dimensional monochromatic spatial images is described. A solution is offered in
      the form of an improved instrument. The system uses a Czerny-Turner monochromator
      for spectral discrimination and a charge-coupled device (CCD) as the detector. A
      second Czerny-Turner monochromator, with identical dimensions, is added to
      correct the distortion, albeit with a slight loss in spatial resolution. With the
      earlier uncorrected arrangement, spatial resolution was on the order of 0.1 mm
      vertically and 0.3 mm horizontally, with a magnification of 0.52. With the same
      magnification, the new, corrected system offers spatial resolution of 0.1 mm
      vertically and 0.4 mm horizontally.

PMID- 16454913
TI  - Measurement of concrete strength using the emission intensity ratio between
      Ca(II) 396.8 nm and Ca(I) 422.6 nm in a Nd:YAG laser-induced plasma.
AB  - An experiment to investigate the potential of a laser-induced plasma method for
      determining concrete compressive strength was conducted by focusing a Nd:YAG
      laser on concrete samples with different degrees of compressive strength. This
      technique was developed in light of the role of the shock wave in the generation
      of a laser-induced plasma. It was found that the speed of the shock front depends
      on the hardness of the sample. It was also found that a positive relationship
      exists between the speed of the shock front and the ionization rate of the
      ablated atoms. Hence, the ratio of the intensity between the Ca(II) 396.8 nm and
      Ca(I) 422.6 nm emission lines detected from the laser-induced plasma can be used
      to examine the hardness of the material. In fact, it was observed that the ratio
      changes with respect to the change in the concrete compressive strength. The
      findings also show that the ratio increases with time after the cement is mixed
      with water.

PMID- 16454914
TI  - Observations in collinear femtosecond-nanosecond dual-pulse laser-induced
      breakdown spectroscopy.
AB  - In the work reported herein, we have combined a short-lived femtosecond laser
      induced plasma (LIP) and a longer-lived nanosecond LIP in a collinear pulse
      configuration to examine the source(s) of atomic emission and signal-to-noise
      enhancement in dual-pulse laser-induced breakdown spectroscopy (LIBS). Initial
      studies indicate that the primary source of dual-pulse LIBS enhancement in the
      collinear configuration may in large part be a matter of pulse focus; focusing on
      the sample surface, for example, yields atomic emission enhancements whose
      lifetime correlates reasonably well with the femtosecond LIP emissive lifetime,
      suggesting that plasma-plasma coupling may play an important role at that pulse
      focus. At a second "optimal" focal position above the sample surface,
      alternatively, atomic emission and signal-to-noise enhancements correlate quite
      well with the nitrogen and oxygen atomic emission reductions previously seen
      following use of a femtosecond air spark and a nanosecond ablative pulse in the
      orthogonal dual-pulse configuration, suggesting that pressure or number density
      reductions due to femtosecond LIP formation in air may be significant at that
      pulse focus.

PMID- 16454915
TI  - Resonance-enhanced multiphoton ionization time-of-flight mass spectrometry for
      detection of nitrogen containing aliphatic and aromatic compounds: resonance
      enhanced multiphoton ionization spectroscopic investigation and on-line
      analytical application.
AB  - Resonance-enhanced multiphoton ionization (REMPI) combined with time-of-flight
      mass spectrometry (TOFMS) is an analytical method capable of on-line monitoring
      of trace compounds in complex matrices. A necessary prerequisite for substance
      selective detection is spectroscopic investigation of the target molecules.
      Several organic nitrogen compounds comprising aliphatic and aromatic amines,
      nitrogen heterocyclic compounds, and aromatic nitriles are spectroscopically
      investigated with a tunable narrow bandwidth optical parametric oscillator (OPO)
      laser system providing a scannable wavelength range between 220 and 340 nm. These
      species are known as possible precursors in fuel-NO formation from combustion of
      solid fuels such as biomass and waste. A newly conceived double inlet system was
      used in this study, which allows rapid change between effusive and supersonic
      molecular beams. The resulting REMPI spectra of the compounds are discussed with
      respect to electronic transitions that could be utilized for a selective
      ionization of these compounds in complex mixtures such as combustion and process
      gases. The practicability of this approach is demonstrated by wavelength selected
      on-line REMPI-TOFMS detection of aniline and cyanonaphthalene in the burning
      chamber of a waste incineration plant. REMPI mass spectra recorded at different
      excitation wavelengths as well as variations in time show the utilization of
      species-selective REMPI-TOFMS detection for on-line monitoring of crucial
      substances in pollutant formation.

PMID- 16454916
TI  - Determination of active pharmaceutical ingredients by heteroatom selective
      detection using inductively coupled plasma mass spectrometry with ultrasonic
      nebuilization and membrane desolvation sample introduction.
AB  - The combination of ultrasonic nebulization with membrane desolvation (USN-MD) is
      utilized to determine active pharmaceutical ingredients (API) by heteroatom
      inductively coupled mass spectroscopy (ICP-MS) detection. Ultrasonic nebulization
      provides efficient sampling while use of the membrane desolvator acts to reduce
      solvent-based interferences. This approach reduces interferences sufficiently so
      that a standard argon ICP-quadrupole MS can be utilized. Examined APIs and
      associated heteroatoms included: phosphomycin (P), amoxicillin (S),
      chlorpropamide (Cl), and ofloxacin (F). The optimum plasma r.f. powers for P, S,
      and Cl were in the 1000 to 1200 watts range. The high ionization energy of F
      required that the plasma be operated at 1500 W. The 16O2+ interference at mass 32
      precluded determinations using the sulfur-32. The sulfur-34 (4.2% natural
      isotopic abundance), however, was relatively free of isobaric interferences.
      Interferences were relatively small at the mass 35 isotope of Cl, but increased
      with higher ICP r.f. powers. Overlaps were significant at the masses of
      monoisotopic species, fluorine-19 and phosphorus-31. Detection limits for P, S,
      Cl, and F of 2, 3, 90, and 3000 ng/mL, respectively, were generally lower than
      those produced with other quadrupole systems and comparable to or better than
      values published utilizing high-resolution instruments.

PMID- 16454917
TI  - Limitations arising from two-photon absorption of solvent in pulsed-laser thermal
      lens detection: determination of the two-photon absorption coefficient of ethanol
      at 266 nm.
AB  - Two-photon absorption of the solvent under pulsed-laser excitation at 266 nm
      produces a high background thermal lens signal interfering with the analyte
      signal. Discrimination of both solvent and analyte signals along with calibration
      of the photothermal response has allowed the determination of the two-photon
      absorption coefficient of ethanol. The obtained value, 3.0x10(-10) cm W-1, is
      close to the literature values obtained from transmittance measurements using
      picosecond or femtosecond laser pulses.

PMID- 16454918
TI  - Frequency domain analysis for fluorescence recovery after photobleaching.
AB  - Fourier transformation is evaluated as a means of improving precision in the
      analysis of fluorescence-recovery-after-photobleaching (FRAP) data. Simulations
      of FRAP data of 2m points, where m is an integer, are Fourier transformed to
      obtain the frequency domain data. Analogous to frequency domain techniques in
      nanosecond spectroscopy, frequency domain analysis of FRAP data is shown to
      provide more precise results. For a single exponential decay acquired over a time
      window of five decay constants, frequency domain analysis increases the precision
      by six fold without requiring that any more data be acquired. For a double
      exponential decay with decay constants that differ by a factor of two and noise
      of 5% relative standard deviation, time domain analysis is unable to distinguish
      this from a single exponential decay (chi2=1.1), whereas frequency domain
      analysis reveals that it does not fit to a single exponential decay (chi2=2.5).
      For a double exponential decay with five-fold differing decay constants, improved
      precision is obtained in the frequency domain for both of the decay constants, as
      well as the fractional amount of each. In contrast to nanosecond spectroscopy,
      the FRAP analysis described here combines the higher precision of the frequency
      domain with the direct observation in the time domain to facilitate the
      assessment of artifacts.

PMID- 16454919
TI  - Spectral simulation study on the influence of the principal component analysis
      step on principal component regression.
AB  - Principal component regression (PCR) is unique in that the principal component
      analysis (PCA) step is explicitly involved in the central part of the method. In
      the present paper, the PCA part is examined in order to study the influence of
      noise in spectra on PCR by spectral simulation. It has been suggested, as a
      result, that PCR calibration would have a large inaccuracy when the estimated
      number of basis factors analyzed by the eigenvalue method is less than that by
      cross-validation, which was studied by use of synthesized spectra. This
      instability is because the minute noise is largely enhanced by the PCA
      calculation via the normalization of loadings. At the same time, the noise
      enhancement by PCA has also been characterized to influence the estimation of
      basis factors.

PMID- 16454920
TI  - Chemiluminescent reactions of nickel, iron, and cobalt carbonyls with ozone.

PMID- 16454924
TI  - Italian Law 40/2004: a view from the 'Wild West'.
AB  - The passage of Law 40/2004 in Italy dramatically affected the manner in which
      assisted reproduction is conducted there. A recent attempt to modify this highly
      restrictive legislation failed to gain popular support and was defeated in a 2005
      referendum. The public's desire to regulate the field of IVF is probably a result
      of growing concern over the use and misuse of the technology as portrayed in the
      popular press and media. Practitioners using this technology throughout the world
      should take note of the impact legislation brings upon the delivery and
      accessibility of care, and be appreciative of the social sensitivity of the
      general population regarding the safe guarding of human embryos.

PMID- 16454926
TI  - Recombinant gonadotrophins in reproductive medicine: the gold standard of today.
AB  - Since the early 1980s when gonadotrophins were first routinely used in ovarian
      stimulation regimens, there have been important advances in pharmaceutical
      product development, leading to the availability today of highly purified and
      consistent human gonadotrophins produced by recombinant technology, that have
      benefited cycle management and treatment outcomes. This 'evolution' has
      introduced scientifically robust and 'state of the art' processes and equipment
      to ensure that the product is consistent, pure and safe, and is the optimal way
      to reduce risk of any viral, protein, and bacterial contamination. Production of
      human proteins by recombinant technology has resulted in improvements in product
      purity, consistency and delivery as well as enabling the design of future
      generations of gonadotrophins (e.g. longer-acting forms and orally active
      mimetics).

PMID- 16454927
TI  - Interest of pentoxifylline in ICSI with frozen-thawed testicular spermatozoa from
      patients with non-obstructive azoospermia.
AB  - Selection for intracytoplasmic sperm injection (ICSI) of viable frozen-thawed
      testicular spermatozoa obtained from patients suffering from non-obstructive
      azoospermia is very often long, difficult and sometimes impossible. The purpose
      of this study was to determine if the use of pentoxifylline (PF) could facilitate
      this selection in stimulating sperm motility. From January 2000 to December 2004,
      108 ICSI cycles with non-obstructive azoospermia were performed. From these 108
      cycles, in 64 cycles where no motile spermatozoa were observed or when the time
      search per spermatozoa was above 20 min, 1.5 mmol/l PF was used for 10 min,
      whereas the 44 other ICSI cycles were performed using spontaneously motile
      spermatozoa (control group). In all cases, PF either initiated the motility when
      no motile spermatozoa were observed, or stimulated the motility, reducing
      dramatically the time search per spermatozoa. The total fertilization rate was
      54.2% versus 66.7% in the control group (P < 0.02). Twenty-nine pregnancies out
      of the 64 PF cycles (45.3% per cycle) occurred, including 20 deliveries of 23
      healthy children and eight ongoing pregnancies, whereas 12 pregnancies were
      obtained in the control group (27.3% per cycle), including nine deliveries of 13
      healthy children. In conclusion, in 100% of cycles pentoxifylline allows the
      selection of viable frozen-thawed testicular spermatozoa with the same outcome
      after ICSI as that observed with fresh ejaculated spermatozoa.

PMID- 16454928
TI  - High-magnification ICSI overcomes paternal effect resistant to conventional ICSI.
AB  - Previous studies have shown that repeated intracytoplasmic sperm injection (ICSI)
      failures can be caused by a paternal effect. Other studies have suggested that
      ICSI results are compromised if morphologically abnormal spermatozoa are injected
      into oocytes. This study was undertaken to evaluate the usefulness of a high
      magnification optical system to select spermatozoa to be used for ICSI (high
      magnification ICSI) in couples with repeated conventional ICSI failures. Couples
      with two or more previous conventional ICSI failures underwent an additional
      conventional ICSI attempt, followed by a high-magnification ICSI attempt. The
      outcomes of the two sequential attempts were compared. In 72 of these patients,
      sperm DNA integrity was assessed. In the whole group of 125 couples with repeated
      ICSI failures, high-magnification ICSI improved clinical outcomes (pregnancy,
      implantation, delivery and birth rates) without affecting biological outcomes
      (fertilization and cleavage rates, embryo morphology). The improvement of
      clinical ICSI outcomes was evident both in patients with an elevated degree of
      sperm DNA fragmentation and in those with normal sperm DNA status. It is
      concluded that high-magnification ICSI improves clinical outcomes in couples with
      previous repeated conventional ICSI failures.

PMID- 16454930
TI  - Luteal phase characteristics following GnRH antagonist or agonist treatment - a
      comparative study.
AB  - Due to inherent differences between gonadotrophin-releasing hormone (GnRH)
      antagonists and agonists, their late effect on ovarian steroidal production
      during the luteal phase of IVF cycles may differ. The aim of this study was to
      characterize and compare the luteal phase hormonal profile after the use of GnRH
      antagonists or agonists in ovarian stimulation protocols for IVF, in non
      conception cycles, to avoid the effect of human chorionic gonadotrophin (HCG)
      during the luteal phase in conception cycles. Seventy-eight normo-ovulatory
      patients <35 years old, undergoing IVF due to male or tubal infertility were
      randomly allocated either to a GnRH antagonist (study group) or GnRH agonist
      treatment (control group). Similar standard luteal support was given to all
      patients, using vaginal micronized progesterone. In non-conception cycles, no
      statistically significant differences were found comparing luteal phase.
      oestradiol or progesterone levels in the study and control groups. No
      statistically significant differences were found comparing the hormonal profile
      dynamics, the mid-luteal (HCG day +8) oestradiol/progesterone ratio and the
      percentage of mid-luteal oestradiol decline between the study and control groups.
      In conclusion, similar characteristics and dynamics of luteal phase oestradiol
      and progesterone were demonstrated comparing ovarian stimulation for IVF using
      GnRH agonist or antagonists, under similar luteal support.

PMID- 16454931
TI  - Elevated oestradiol concentrations are not associated with increased first
      trimester miscarriage rates of singleton gestations conceived by assisted
      conception treatment.
AB  - The study evaluated the impact of elevated oestradiol concentrations on pregnancy
      loss during the first trimester in singleton gestations conceived via ovarian
      stimulation and intracytoplasmic sperm injection (ICSI). Following determination
      of oestradiol concentrations during 6478 ICSI cycles, patients were assorted by
      oestradiol percentile. Hyper-responders were defined as patients having peak
      oestradiol concentrations over the 90th percentile (>4200 pg/ml, 685 cycles),
      moderate responders were defined as patients having peak oestradiol
      concentrations between the 75th and 90th percentiles (3250-4200 pg/ml, 958
      cycles) and normal responders were defined as patients having peak oestradiol
      concentrations between the 25th and 75th percentiles (1350-3250 pg/ml, 3325
      cycles). The relationship between first trimester miscarriage rates and
      oestradiol percentiles was analysed in 1184 singleton gestations. Pregnancy rate
      was significantly lower in normal responders (54.4%) than in moderate (58.8%, P =
      0.02) and hyper-responders (60.9%, P = 0.003), but there were no intergroup
      differences in miscarriage rate (19.6%, 17.1%, and 16.8%, respectively). Although
      women with severe ovarian hyperstimulation syndrome had a miscarriage rate of
      40%, this rate did not differ significantly from the miscarriage rates of the
      other groups. The findings suggest that high oestradiol concentrations during
      ovarian stimulation do not expose singleton pregnancies to an increased risk of
      miscarriage during the first trimester.

PMID- 16454932
TI  - Unusual presentation of a woman with polycystic ovaries and complex endometrial
      pathology.
AB  - A 28-year-old woman with polycystic ovarian syndrome (PCOS) had attempted four
      assisted conception treatments, all of which were complicated by lack of response
      of the endometrium to the hypo-oestrogenic state induced with gonadotrophin
      releasing hormone analogue (GnRHa). Consequently, two treatment cycles were
      abandoned, one prior to the ovulation induction of a fresh IVF treatment and the
      other prior to oestrogen replacement for a frozen-thawed embryo transfer
      treatment cycle. Extended down-regulation eventually resulted in endometrial
      thinning and allowed completion of the other two treatments, but the outcome was
      negative. A targeted mid-cycle ultrasound scan in a natural cycle at follow-up
      showed thick, non-homogenous endometrium. A repeat hysteroscopy on this occasion
      showed abnormal endometrium with chalk-like deposits. Histological diagnosis was
      chronic endometritis and endometrial hyperplasia with focal atypia.
      Microbiological tests, including those for Mycobacterium tuberculosis, were
      negative. Because of atypical endometrial hyperplasia, this patient is currently
      under close follow-up by the original referring team. This case highlights
      inherent endometrial pathology presenting as non-responding endometrium to
      hormonal down-regulation, the limitations of conventional ultrasound scans, and
      the complimentary role of concomitant hysteroscopy in the correct identification
      of endometrial lesions that may negatively affect the assisted conception
      treatments.

PMID- 16454933
TI  - Ovarian stromal vascularity is not predictive of ovarian response and pregnancy.
AB  - The role of ovarian stromal vascularity in the prediction of the ovarian response
      and pregnancy in infertile women was evaluated by comparing age of women, body
      mass index (BMI), basal FSH concentration, antral follicle count (AFC) and
      ovarian stromal vascularity indices measured by three-dimensional power Doppler
      ultrasound. A total of 111 women in their first IVF cycle were analysed. They
      were aged <40 years with basal FSH concentration <10 IU/l on recruitment for IVF
      treatment. AFC, mean ovarian volume and mean ovarian 3D power Doppler flow
      indices were determined on day 2 of the treatment cycle prior to a standard
      regimen of ovarian stimulation. Ovarian response was represented by the number of
      oocytes, serum oestradiol, the duration and dosage of gonadotrophins. AFC
      achieved the best predictive value in relation to the number of oocytes obtained,
      followed by age of women and BMI. Basal FSH concentration was the only predictive
      factor for the duration and dosage of gonadotrophin used. Mean ovarian 3D power
      Doppler flow indices were not predictive of pregnancy in a multiple logistic
      regression analysis. Ovarian 3D power Doppler flow indices measured after
      pituitary down-regulation were not predictive of the ovarian response and
      pregnancy in the IVF treatment.

PMID- 16454934
TI  - Developmental competence of transported in-vitro matured macaque oocytes.
AB  - This study examines in-vitro maturation (IVM) in a non-human primate model,
      Macaca fascicularis. The animals had hormonal injections and laparoscopic oocyte
      retrieval (OR)) at 12- and 24- h after human chorionic gonadotrophin (HCG). The
      immature oocytes were placed in tightly capped tubes containing pre-equilibrated
      IVM medium and transported for 5 h in a dry portable 37 degrees C incubator
      without CO2 supplement. Meiotic spindle was observed at 36-38- h post-HCG by
      polarized microscopy in 72 and 84.5% of mature oocytes collected at 12- and 24- h
      post-HCG oocyte retrieval intervals respectively. However, abnormal spindle
      formations were detected in some IVM oocytes by confocal microscopy. The IVM
      oocytes were also randomly selected for (i) intracytoplasmic injection with
      frozen-thawed epididymal M. fascicularis spermatozoa and (ii) nuclear transfer
      (NT) with fresh M. fascicularis cumulus cells. Embryonic development of sperm
      injected embryos was not affected by the 12- and 24- h post-HCG oocyte retrieval
      intervals (22.5 versus 27.9% respectively). However, embryonic development of NT
      embryos was significantly affected by the 12- h post-HCG oocyte retrieval
      interval (4.5 versus 31.7% respectively; P < 0.01). In conclusion, IVM of monkey
      oocytes in a dry portable incubator for 5 h did not affect the maturation rate.
      However, the ability of primate oocytes to develop after somatic cell nuclear
      transfer was affected by oocyte retrieval time post-HCG.

PMID- 16454935
TI  - Early pregnancy loss is significantly higher after day 3 single embryo transfer
      than after day 5 single blastocyst transfer in GnRH antagonist stimulated IVF
      cycles.
AB  - The current study aimed to investigate whether single day-3 embryo transfer (SET)
      results in higher early pregnancy loss (EPL) than single blastocyst transfer
      (SBET). A total of 896 patients underwent 1103 IVF cycles with a gonadotrophin
      releasing hormone (GnRH) antagonist protocol. In 603 cycles (D3 group) a single
      embryo on day 3 of the embryo culture was transferred, whereas in the remaining
      500 cycles a single blastocyst was transferred on day 5 (D5 group).
      Multifollicular ovarian stimulation was performed with a GnRH antagonist protocol
      starting on day 6. SET resulted in 209 pregnancies (34.7%), compared with 221
      pregnancies (44.2%) for SBET. Early pregnancy loss rate was significantly higher
      with SET compared with SBET (26.8% versus 17.2%, P = 0.017) and ongoing
      implantation rate was also significantly higher with day 5 compared with day-3
      embryo transfer (OR:1.68, 95% confidence interval:1.31-2.18). Sub-optimal embryo
      selection for transfer on day 3, in addition to asynchronization between altered
      endometrium and early exposure of cleavage-stage embryos, might explain the above
      difference. Nevertheless, the higher implantation potential of the blastocyst
      questions the rationale behind performing single embryo transfer on day 3 of
      embryo culture in women under 36 years old.

PMID- 16454937
TI  - Vitrification of mouse pronuclear oocytes with no direct liquid nitrogen contact.
AB  - The ability to routinely cryopreserve human oocytes and embryos represents a
      significant advancement in the field of assisted reproductive technology.
      Although the method of slow freezing is commonly employed, research on the
      alternative technique of vitrification is promising. Vitrification involves
      incubation of the cell in a cryoprotectant rich solution, which permits a glass
      like state to occur almost instantaneously in liquid nitrogen. A number of
      different techniques have been invented for holding oocytes and embryos in the
      cryoprotectant solution during rapid vitrification and subsequent storage. Most
      of these involve direct contact with liquid nitrogen. Recently, concerns have
      been raised regarding the sterility of such a method and the potential of viral
      contamination from the liquid nitrogen. The present study shows that the
      previously reported Cryoloop method can be used to vitrify and store embryos
      without direct liquid nitrogen contact (during vitrification and storage). When
      such vitrified embryos are warmed, they are capable of subsequent development
      comparable with non-vitrified embryos.

PMID- 16454938
TI  - Parameters predicting the implantation rate of thawed IVF/ICSI embryos: a
      retrospective study.
AB  - Single embryo transfer is becoming increasingly popular in IVF/ICSI. More
      IVF/ICSI cycles therefore include freezing of high quality embryos, and the
      cumulative effect of such cycles becomes more important. To improve the results
      obtained using frozen-thawed embryos, the predictive value of embryo and patient
      characteristics was analysed retrospectively. Excess embryos were frozen on day 2
      according to routine procedures and thawed 24 h before transfer. The women were
      either treated with oestradiol/progesterone, or the transfer took place after a
      natural cycle. Of 1777 embryos thawed, 1360 survived (survival rate 76.5%). In
      the 410 transfer cycles, 819 embryos were transferred, giving 109 positive serum
      HCG tests and 69 clinical pregnancies. The implantation rate was 10.4%. Five
      parameters were positively related to implantation: (i) four or more cells at the
      freezing time (day 2); (ii) resumption of mitosis after thawing; (iii) more than
      six cells at transfer (day 3); (iv) assisted hatching and (v) child in a previous
      fresh cycle. The relative predictive value of these parameters may be a guideline
      for the selection of embryos used for transfer. Assisted hatching may become
      routine in freeze-thaw cycles if its utility is confirmed in subsequent studies.

PMID- 16454940
TI  - Relationship between embryo quality and aneuploidies.
AB  - Many high-grade embryos selected for transfer according to their morphological
      evaluation were detected to have chromosomal abnormalities after aneuploidy
      screening for infertility by preimplantation genetic diagnosis (PGD). The aim of
      this study was to detect if there is any correlation between embryo quality and
      genetic status. The chromosomal status of the day three embryos was studied by
      multicolour fluorescence in-situ hybridization for chromosomes 13, 18, 21, X and
      Y. PGD was performed on 132 patients for 1107 embryos. The correlation between
      embryo quality and aneuploidy was analysed. The analysis showed that a large
      proportion of normal embryos (50.7%, n = 280) were grade I. In addition, a
      considerably high proportion of aneuploid embryos (36.1%, n = 83) were evaluated
      as grade I. There was a significant relationship between PGD results and embryo
      grades (P = 0.001). Of the 69 polyploid embryos, 21.7% were grade I and 37.8%
      were grade II. Of the 83 haploid embryos, 27.8% were grade I and 34.9% were grade
      II. Euploidy was positively related to morphological grade of embryo (P = 0.001).
      It was also possible for chromosomally abnormal embryos to have a good
      developmental potential, and they could be selected for embryo transfer unless
      the PGD procedure was applied.

PMID- 16454941
TI  - Preimplantation genetic diagnosis for Pelizaeus-Merzbacher disease with testing
      for age-related aneuploidies.
AB  - Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive demyelinating
      disorder of the central nervous system, caused by mutations of the proteolipid
      protein 1 gene (PLP1 gene). As no specific therapy is available for PMD,
      preimplantation genetic diagnosis (PGD) may be a useful option for couples
      carrying this mutation. PGD was performed for a couple who had had one child with
      the L86P mutation in exon 3 of the PLP1 gene. Because of advanced maternal age,
      PGD for this single-gene disorder was performed together with testing for
      chromosomal abnormalities. Polar bodies and blastomeres were tested for the
      presence of maternal mutation and closely linked markers DXS8020 and PLP5' (CA)n.
      The same blastomeres were also tested for the copy number of chromosomes 13, 16,
      18, 21, 22, X and Y, and five chromosomally abnormal embryos were identified. A
      total of three embryos predicted to be unaffected and free of chromosomal
      disorder were transferred back to the patient, resulting in a twin pregnancy and
      the birth of two healthy female infants confirmed to be free of PMD, representing
      the first PGD for PMD combined with aneuploidy testing.

PMID- 16454942
TI  - Preimplantation HLA typing with aneuploidy testing.
AB  - Preimplantation HLA typing has been introduced for the treatment of affected
      siblings, requiring HLA-identical stem cell transplantation. This was applied
      either in combination with preimplantation genetic diagnosis (PGD) to ensure that
      the preselected HLA-matched embryos were also free of the genetic disorder, or
      without PGD, with the only purpose of selecting and transferring the HLA-matched
      embryos. Because patients requesting preimplantation HLA typing are usually of
      advanced reproductive age, aneuploidy testing allows not only the avoidance of
      the birth of children with chromosomal disorders, but also improvement of the
      reproductive outcome, which is still not sufficiently high in preimplantation HLA
      typing at the present time. This study presents the results of the first
      experience of preimplantation HLA typing combined with aneuploidy testing,
      demonstrating feasibility and impact of aneuploidy testing on the accuracy and
      outcome of preimplantation HLA typing. Of a total of 138 cycles performed, 87
      were combined with PGD and 52 without testing for the causative gene, of which
      aneuploidy testing was performed in 27 cycles, allowing the preselection and
      transfer of only those HLA-matched embryos that were also euploid. Although the
      euploid HLA-identical embryos were available for transfer in only half of these
      cycles, pregnancy and birth of unaffected HLA-identical children were observed in
      approximately half of these cycles, suggesting the potential usefulness of
      incorporating aneuploidy testing into preimplantation HLA typing.

PMID- 16454944
TI  - Reprogramming of human somatic cells by embryonic stem cell cytoplast.
AB  - Somatic cell nuclear transfer (SCNT) provides the basis for the development of
      patient-specific stem cell lines. Recent progress in SCNT suggested the presence
      of reprogramming factors in human embryonic stem (hES) cells, although no method
      is currently available for replacement of nuclei of hES cells by somatic cell
      nuclei. An original technique has been developed, involving the fusion of
      different types of somatic cells with hES cells, which allowed a complete
      replacement of the nuclei of hES cells by nuclei of somatic cells. The resulting
      'cybrids' were demonstrated to have the genotype of the donor somatic cells and
      'stemness' of the recipient hES cells. However, the colonies isolated from the
      resulting fusion contained a mixture of these cybrid cells with the cells with
      the recipient nuclei, as well as hybrid cells containing both donor and recipient
      nuclei, so future purification will be necessary before the technique can be
      considered for future practical application.

PMID- 16454943
TI  - Mitochondrial DNA deletions in primate embryonic and adult stem cells.
AB  - Mitochondrial DNA (mtDNA) mutations occur naturally in skeletal muscle fibers
      from aged rhesus macaques. In addition, mtDNA mutations have been observed in
      germinal vesicle oocytes from fertile monkeys. The goal of this study was to
      determine whether the rhesus macaque mitochondrial common deletion was present in
      oocytes and embryos generated by in-vitro embryo production (IVP), as well as in
      rhesus adult and embryonic stem cell lines. The rhesus common deletion was
      detected in IVP-generated embryos, three IVP-derived embryonic stem cell lines
      (ORMES 1, 2 and 7), one in-vivo-derived embryonic stem cell line (R4) and
      multiple passages of an adult bone marrow stromal cell (BMSC) line. Mitochondrial
      DNA from an adult adipose stromal cell (ATSC) line was compared with mtDNA from
      an immortalized line transfected with a retroviral vector expressing telomerase,
      ATSC-TERT. Multiple passages of the ATSC line harboured a dramatically higher
      level of the rhesus common deletion than the immortalized ATSC-TERT line.
      Accumulation of mtDNA mutations in oocytes, embryos and subsequent embryonic stem
      cell lines, as well as adult stem cell lines, may contribute to mitochondrial
      dysfunction, and thereby impair ATP production. The authors believe this
      information establishes a compelling argument for the parallel development of
      embryonic stem cell technology in non-human primates and humans.

PMID- 16454945
TI  - Derivation of clinical-grade human embryonic stem cells.
AB  - Embryonic stem cells proliferate in vitro while maintaining an undifferentiated
      state, and are capable of differentiating into most cell types under appropriate
      conditions. These properties imply great potential in the treatment of various
      diseases and disabilities. In fact, the first clinical trials with hESC for
      treating spinal cord injuries will begin next year. However, therapeutic
      application of human embryonic stem cell derivatives is compromised by the
      exposure of existing lines to animal and human components, with the subsequent
      risk of contamination with retroviruses and other pathogens, which can be
      transmitted to patients. The scientific community is striving to avoid the use of
      xenogeneic or allogeneic components in the process of derivation new hESC lines.
      This review summarizes attempts that have been made to avoid these contaminants
      and the breakthroughs achieved in the derivation of clinical-grade hESC that
      could be used for therapeutic purposes.

PMID- 16454946
TI  - Derivation and characterization of four new human embryonic stem cell lines: the
      Danish experience.
AB  - In September 2003, legislation approved in Denmark legalized work on surplus
      human embryos from IVF for clinical purposes to establish human embryonic stem
      (ES) cell cultures. The aim of this study was to establish such stem cell lines.
      Fresh surplus embryos were donated after informed consent from the donors.
      Embryos were cultured into blastocysts and using the immunosurgery procedure,
      inner cell masses were isolated and cultured on irradiated human foreskin
      fibroblasts in KnockOut D-MEM supplemented with KnockOut Serum Replacement, bFGF,
      and LIF. Within a period of 12 months, 198 embryos were donated. Four isolated
      inner cell masses developed into putative ES cell lines, CLS1, CLS2, CLS3, CLS4,
      which have now been continuously cultured for eight months, corresponding to 30
      passages. These cells expressed markers for undifferentiated human ES cells:
      stage-specific embryonic antigen-4, tumour-related antigen (TRA)-1-60, TRA-1-81,
      OCT4, NANOG, SOX2, and FGF4. The cells expressed high levels of telomerase
      activity, had a normal karyotype, and have been successfully cryopreserved and
      thawed. Finally, the cells displayed the potential to differentiate in vitro into
      cell types originating from all three germ layers. It is thought that the cell
      lines described in this study are the first human ES cells established in
      Denmark.

PMID- 16454948
TI  - Dealing with the menopause: the French exception.

PMID- 16454949
TI  - Laparoscopic management of unicornuate uterus with non-communicating rudimentary
      horn (three cases).
AB  - This article describes the laparoscopic management of unicornuate uterus with a
      non-communicating rudimentary horn in three women who presented with lower
      abdominal pain and dysmenorrhoea. The patients were managed with laparoscopic
      removal of the rudimentary horn along with the ipsilateral salpinx. No
      complications were noted intraoperatively and the patients remain asymptomatic.

PMID- 16454952
TI  - [Breast cancer].

PMID- 16454953
TI  - [Treatment of spontaneous dissociated vertical deviation with the pharmacological
      penalization of the fixing eye].
AB  - BACKGROUND: Dissociated vertical deviation (DVD) is a common innervational entity
      frequently found in patients with congenital endotropia. It is characterized as
      being bilateral, asymmetric, and to a greater extent, in the non-fixating eye. It
      can be compensatory or non-compensatory. In the majority of cases, surgery is the
      treatment of choice, but spontaneous appearance of DVD is a common occurrence
      after surgery, sometimes to a degree similar to that prior to surgery. OBJECTIVE:
      Our aim was to evaluate the behavior of dissociated vertical deviation with
      penalization of the fixating eye. MATERIAL AND METHODS: An experimental and
      longitudinal study was conducted in which patients with spontaneous DVD were
      included, whether or not associated with horizontal deviation, with or without
      previous surgery. Atropine (1%) was applied every 24 h in the fixating eye for 3
      months and DVD presence, magnitude, and spontaneity were evaluated at 15 days, 1
      month, 3 months, and 1 month after penalization suspension. RESULTS: Eight
      patients were included. DVD magnitude decreased with penalization (p = 0.02) and
      remained unchanged when atropine was suspended (p = 0.6). With regard to
      decompensatory phases, DVD shifted from spontaneous to non-spontaneous during
      penalization (p = 0.01); when this was eliminated, deviation showed
      decompensation again (p = 0.03). CONCLUSIONS: Fixating eye penalization with 1%
      atropine reduces DVD magnitude and decompensatory phases during follow-up.

PMID- 16454954
TI  - [Esophageal perforation].
AB  - OBJECTIVE: We describe our experience in the management of esophageal
      perforation. MATERIAL AND METHODS: Retrolective study of the esophageal
      perforation patients, managed from January 1999 to December 2003. Analyzed
      variables were age, sex, aetiology, time of diagnosis and treatment, as well as
      ancillary methods employed, mode of treatment and morbidity and mortality.
      RESULTS: We found 13 patients: eight males (61.54%) and five females (38.46%),
      with an average age of 36.07 years with standard deviation of 19.77. Penetrating
      trauma was the leading cause in six cases, continued by iatrogenic perforation in
      four, Boerhaave's syndrome in one, foreign body in one, and blunt abdominal
      trauma in one. The principal symptom was pain in 84.61% of the cases. The
      esophagogram confirmed diagnosis in six cases (46.15%). The diagnosis was
      accomplished early in eight patients (61.54%) and late in five patients (38.46%).
      Nonsurgical treatment was carried out in two cases (15.38%) and surgical in 11
      patients (84.62%). The average hospital stay was 22.45 days. Mortality in general
      was 15.38%, 0% for those with an early diagnosis and management and 40% for those
      delayed. CONCLUSIONS: An early diagnosis of esophageal perforation with the
      appropriate management (surgical or nonsurgical) will considerably diminish
      patient morbidity and mortality. A treatment choice could not be defined for the
      early or late diagnosis, but if surgical treatment is undertaken, adequate
      drainage for the perforation should be instituted as one of its principles.

PMID- 16454955
TI  - [Lymphatic mapping and sentinel lymph node biopsies in order to avoid axilar
      dissection in early breast cancer].
AB  - OBJECTIVE: To present the characteristics of women with early breast cancer and
      clinically negative ganglia who were submitted to LM and SLNB in order to select
      the positive cases for axilar dissection and to identify the negative cases.
      MATERIAL AND METHODS: Cases included patients who attended the Breast Tumor
      Service of the Oncology Hospital of the National Medical Center of the Mexican
      Social Security Institute from March 1, 2002, to April 30, 2004. Women with early
      breast cancer and clinically negative ganglia (N0) were included, with out
      previous treatment and without previous biopsies. All cases were submitted to LM
      and SLNB with patent blue or double-blue technique and gamma probe. The lymph
      nodes were evaluated histopathologically and negative or positive results were
      considered, in order to determine whether or not to undertake the axilar
      dissection. No cases were excluded. RESULTS: Sixty cases were reviewed with an
      average age of 51 years. The average size of the ganglia was 1.9 cm, with stages
      EC-0: 9%, EC-I: 33%, EC-IIA: 58%. Sentinel lymph nodes were found in 100% and 95
      ganglions were dissected, for an average of 1.6 per procedure. The histopathology
      was definitive in 19 women with metastasis (32%) and in 41 women with negative
      ganglia (68%). The results of transoperative histopathology were correlated with
      the histopathology report (one false positive and six false negative cases),
      sensitivity of 68.4%, specificity of 97.5%, positive predictive value 92.8% and
      negative predictive value 86.9%. CONCLUSIONS: LM and SLNB avoided radical axilar
      dissection in 68% of the cases and reduced the cost in 10% of the cases.

PMID- 16454956
TI  - [Gallstone ileus].
AB  - OBJECTIVE: To determine the frequency of gallstone ileus as a cholelithiasis
      complication and likely cause of intestinal obstruction, as well as the factors
      that can influence morbidity and mortality of these patients in our hospital.
      MATERIAL AND METHODS: The files of patients undergoing cholecystectomy, as well
      as of those patients surgically treated for intestinal obstruction between
      January 2001 and December 2003, were reviewed. We analyzed the files of patients
      with gallstone ileus for the following characteristics: age, sex, time of
      evolution, signs and symptoms, diagnosis, APACHE II, concomitant diseases, mode
      of treatment, obstruction/fistula site and morbidity and mortality. RESULTS: A
      total of 1054 patients for cholelithiasis and 189 for intestinal obstruction were
      treated surgically. Of these, there were seven cases of gallstone ileus: six
      females (85.7%) and one male (14.3%). Average age was 62.85 years (range: 39 to
      89 years). Average time of evolution was 4.85 days until the surgical
      intervention. Preoperative diagnosis ws carried out in five of seven cases
      (71.42%). APACHE II for severity was present in all patients >60 years old;
      71.42% of the cases presented some associated chronic illness. Surgical procedure
      was enterolithotomy without dismantlement of the fistula in five of seven cases
      and in two of seven cases surgery was carried out in a single stage. Obstruction
      occurred in ileum (four of seven cases), jejunum (two of seven cases), and one in
      the duodenum; the fistula occurred in duodenum in five cases and two cases in the
      stomach. Morbidity and general mortality were, respectively, 28.57% and 14.28%.
      CONCLUSIONS: We found a frequency of 0.66% of gallstone ileus as a complication
      of cholelithiasis (7/1054 cases) and 3.70% as a case of intestinal obstruction
      (7/189 cases), increasing to 12% in patients >60 years. The factors that elevated
      the morbidity and mortality were a delay in seeking medical care, patients > 60
      years, associated chronic illnesses and an APACHE II for severity.

PMID- 16454957
TI  - [Acute intestinal ischemia serum markers for the diagnosis of acute
      appendicitis].
AB  - INTRODUCTION: Acute appendicitis is the most common surgical emergency of the
      abdomen, but is still misdiagnosed in a large number of cases because of the the
      poor accuracy of the different radiologic and laboratory exams. Like in
      intestinal ischemia, an ischemic factor causes necrosis of the appendiceal wall
      and this favors the release of particular biochemical serum markers. OBJECTIVE:
      To evaluate the efficacy of intestinal ischemia serum markers as a diagnostic
      test for acute appendicitis. MATERIAL AND METHODS: Two hundred patients were
      studied prospectively. Depending on results of the examination by a surgeon,
      patients underwent surgery for acute appendicitis. Serum levels of amylase,
      lactic dehydrogenase, alkaline phosphatase, alanine transaminase, aspartate
      transaminase and leucocyte count were taken preoperatively. We then compared the
      results with histopathologic findings. RESULTS: Appendicitis was confirmed in 176
      patients. Leukocytes had the highest sensitivity but very low specificity.
      Amylase and DHL were very specific but their sensitivity was poor. Differential
      leukocyte count had the highest positive predictive value. CONCLUSIONS: Serum
      enzymes of intestinal ischemia are not useful markers for the diagnosis of acute
      appendicitis. Leukocyte count is still the most useful serum marker of
      appendicitis.

PMID- 16454958
TI  - [Traumatic perforation of the anorectal canal].
AB  - INTRODUCTION: Traumatic perforation of the anorectal canal in children is
      relatively uncommon. There may be difficulties in recognizing or properly
      treating such injuries because their severity may not be reflected accurately by
      the external appearance of the perineum. MATERIAL AND METHODS: This was a
      retrospective survey of 19 children with anorectal rupture injuries secondary to
      blunt trauma and perforating mechanisms. RESULT: Sixteen (89.4%) were male and 15
      (77.0%)suffered perforation after al fall on a sharp tool. All were admitted more
      than 12 hours after accident. Twelve (63.0%) had transanal extra-peritoneal
      injuries and 13 (68.4%) patients underwent colostomy. CONCLUSIONS: The majority
      of these perforations are caused by falls at play. The current standard
      principles in the treatment of anorectal injuries in children and wound drainage,
      broad-spectrum antibiotics and frequently fecal diversion.

PMID- 16454959
TI  - [Correlation of age, IGF-1 serum levels, muscular mass index and their influence
      as determinants of isokinetic variables in patients with osteoporosis].
AB  - INTRODUCTION: Bone and skeletal muscle mass loss is related to age. Mechanisms by
      which they interact have not been well established. OBJECTIVE: To establish a
      relationship of age with serum levels of IGF-1, skeletal muscle and appendicular
      muscle mass index, and their influence in isokinetic parameters in osteoporotic
      female patients. MATERIAL AND METHODS: Pearson correlation coefficient and linear
      regression analyses were used. RESULTS: There were 38 patients with a mean age of
      65.16 years (range: 50-84 years), mean appendicular skeletal mass index (ASMI) of
      6.3 kg/m2 (range: 4.3-8.3) and mean skeletal mass index (SMI) of 12.4 kg/m2
      (range: 9.6-15.7), mean serum IGF-1 levels of 82.97 ng/ml (range: 22-177). Linear
      regression predicted hip mineral bone density by SMI (p = 0.19) and age (p =
      0.017, r = 0.50). Some isokinetic parameters had a positive correlation for work
      with age. Knee acceleration time had a positive correlation with age.
      CONCLUSIONS: Osteoporosis and sarcopenia may have related pathophysiologic
      mechanisms. Growth factor study must include the influence of sex hormones. Some
      isokinetic parameters are determined by the predominant muscle fiber, skeletal
      mass index and age.

PMID- 16454960
TI  - [Multiresistant Pseudomonas spp. in vitro susceptibility to a combination of two
      antibiotics].
AB  - INTRODUCTION: In vitro antibiotic combination testing would guide therapy
      selection in patients severely affected by multi-drug resistant Pseudomonas.
      OBJECTIVES: In vitro, a two-antibiotic combination susceptible against multi-drug
      resistant Pseudomonas isolated at the Laboratorio Clinico of the Hospital de
      Oncologia, Centro Medico Nacional Siglo XXI in Mexico City were analyzed to
      determine which antibiotic combination showed the best bactericidal activity.
      MATERIAL AND METHODS: During 10 months, 30 multi-drug resistant Pseudomonas
      strains were tested. An automated method was used, including a diluting solution
      with a well-known concentration of a second antibiotic. Quality controls
      recommended by the NCCLS were used. Pseudomonas aeruginosa ATCC 27853;
      Escherichia coli ATCC 25922; and Escherichia coli ATCC 35218. Combinations were
      betalactamics-aminoglycosides; carbapenemis-amikacin; fluoroquinolones-cefepime;
      and ciprofloxacin-ampicillin. RESULTS: Ampicillin-ciprofloxacin combination was
      bactericidal against 100% of the isolates. Cefazolin, cefixime and ticarcillin
      with amikacin: <50%; aztreonam, cefoxilin, cefuroxime, cefotaxime, ceftazidime
      and piperacillin with amikacin: 50-60%; cefepime with gentamicin: 76%; cefepime
      with amikacin: 86%; imipenem and meropenem with amikacin: 70% and 76%; cefepime
      with ciprofloxacin: 83%; cefepime with levofloxacin: 73%. CONCLUSIONS: In vitro
      antibiotic combination susceptibilities against multi-drug resistant bacteria
      would be the only way to guide clinicians to select the best therapy in severe
      infections. We found that the ampicillin-ciprofloxacin combination showed the
      best in vitro effect against multi-drug resistant Pseudomonas.

PMID- 16454961
TI  - [Soft palate transnasal retractor].
AB  - INTRODUCTION: An anterior transoral approach allows the surgeon to access the
      lower portion of the clivus; to the first, second or third thoracic vertebra. It
      is indispensible that the teeth, lips, cheeks and tongue be retracted to avoid
      interposition on the surgical field. This retraction is carried out by means of a
      Dingman separator. Nevertheless, generally the soft palate is elevated with
      sutures through the nasal fossa. Because this invasive method could damage soft
      tissues, we have designed a basket to separate the soft palate from the surgical
      field, thus allowing the surgeon to maneuver with comfort and without damaging
      structures. TECHNIQUE: A 30-cm segment of 22 gauge wire is passed through each
      end of a thin sheet of silicon (4 x 3 x 1.5 cm) forming a basket. With the
      patient under general anesthesia, both free ends of the wire are introduced into
      the buccal cavity in the same manner nasal packing is used to control epistaxis.
      Each end of the wire is slid from the mouth through the nasal fossa to bring them
      outside the face. Traction is placed on both ends of the wire allowing the
      intraoral band of silicon to elevate and hold the soft palate. CLINICAL CASE: We
      present the case of a 64-year-old woman with spastic quadriparesis and
      hyperreflexia predominantly of the upper extremities, in addition to trophic
      changes due to arthritis of long duration. Imaging studies demonstrated
      nonreducible subluxation of the atlantoaxial joint with ventral compression of
      the bulbomedullar union by the odontoid apophysis. Resection of the anterior arch
      of the atlas and apophyses was made via the transoral route, where retraction of
      the soft palate by means of the described basket was employed. The patient did
      not experience significant sequelae as a result of the technique utilized.

PMID- 16454962
TI  - [Radical surgical treatment for bone metastasis from thyroid carcinoma. Report of
      four cases].
AB  - Most patients with thyroid bone metastases have been evaluated in accordance with
      other sites of disease. Overall survival is impacted and the results with
      surgery, radiation therapy, or radioactive iodine show variable results. Four
      cases are presented: three women and one man with an age range of 43-53 years and
      all with radical surgery. Good local control in three of the patients was
      observed. All patients had hormonal suppression with levothyroxine. Radical
      surgery showed an improvement in survival in patients with bone metastases for
      thyroid carcinoma.

PMID- 16454963
TI  - [Hepatic retransplant and acute Budd Chiari syndrome. Case report].
AB  - Hepatic retransplant constitutes 10-20% of all orthotopic hepatic transplants.
      The piggy-back technique was used in hepatectomy with conservation of the
      retrohepatic vena cava. A side-to-side cavo-cavostomy technique is described in
      the case of hepatic congestion or acute Budd Chiari syndrome post-transplant.
      This is an extremely serious condition and can result in death. We present the
      first case of hepatic retransplant performed in Hospital Hermanos Ameijeiras in a
      patient who received who received his first transplant due to non-resectable
      hepatocarcinoma and who required retransplant due to acute rejection and graft
      dysfunction. During retransplant, the Belghiti side-to-side anastomosis technique
      was used to resolve the acute Budd Chiari syndrome that presented itself. Post
      surgical evolution at 18 months was satisfactory without evidence of
      complications of the graft. Acute Budd Chiari syndrome post-transplant can
      satisfactorily be resolved with the Belghiti technique, although it is preferable
      to take prophylactic measures to avoid it.

PMID- 16454964
TI  - [Telemedicine Anahuac. Educational system and health promotion activities].
AB  - Rural telemedicine began in the 1950s in the Papago, Arizona Reservation with the
      program Starphac. The Anahuac University began the program in 2002. In the
      Anahuac, the project was developed to provide specialty consultations in a
      virtual way to a highly marginalized population, creating clinical fields of high
      technology and fulfilling social obligations. The program began in Guerrero and
      was complemented with video conferences to an open population, courses to general
      physicians, continuing medical education, activities to promote health, and
      emergency disaster plans. From May 2002 until the end of 2004, 11,576 general
      consults have been provided and 2,420 specialty consults. The most frequent
      diagnoses in surgery were peptic ulcer disease, cholecystitis, diabetic foot and
      superficial venous insufficiency. The telemedicine program has allowed us to
      bring high specialty consults with great productivity, efficiency, less wait time
      and cost-benefit impact, along with a high quality of humane care. Resident
      physicians do their social service in a positive manner, with a permanent
      consultation office and a program of continuing medical education.

PMID- 16454965
TI  - [Ethics and palliative care in patients with advanced cancer].
AB  - Recent research in both the biology of cancer and the treatment of patients has
      increased the life expectancy of cancer patients with recurrence and who have a
      longer survival rate. Cancer is no longer considered a lethal but a chronic
      disease. More patients survive, but above all there are more patients with
      recurrences thus increasing the need for physical or psychological treatment of
      patients with longer lives. The American Cancer Society reported in 1992 that in
      the U.S. more than 8 million people survived between 4 and 5 years. This produces
      both an ethical and medical challenge for treatment of cancer patients. This
      paper reviews the actual criteria for palliative care: treatment for pain and the
      ethical and psychological treatment of advanced cancer patients and their
      families.

PMID- 16454966
TI  - Dr. Francis Alexander Carron Scrimger.

PMID- 16454967
TI  - President's message. Are we disappearing?

PMID- 16454968
TI  - Alcohol drinking habits and community perspectives on alcohol abuse in the Bella
      Coola Valley.
AB  - INTRODUCTION: This study surveyed the residents of the rural and remote
      communities in the Bella Coola Valley, British Columbia, on their alcohol
      drinking habits and on their opinions as to which of a list of health issues were
      the most important considerations for the well-being of the community. METHODS:
      People aged 17 years and older living in the Bella Coola Valley were asked to
      complete a detailed Health and Quality of Life Survey during the period August
      2001 to May 2002. This included two separate mailouts. Alcohol drinking habits;
      and ratings on whether or not people believed that alcohol abuse, drug abuse,
      family violence, unemployment, sexual abuse and racial discrimination were
      surveyed. RESULTS: A total of 674 adults age 17 years and older (39% response
      rate) completed an 11-page questionnaire. Results from the survey indicate that
      unemployment, alcohol abuse and drug abuse are seen as the most important
      community health problems by the majority of residents. Eighty-eight percent of
      respondents agree or strongly agree that unemployment is a problem; for alcohol
      abuse it was 83%, for drug abuse 77%, for both family violence and sexual abuse
      58%, and for racial discrimination it was 53%. Patterns of drinking habits vary
      considerably between Aboriginal peoples and non-Aboriginal people. More
      Aboriginal respondents abstained from drinking alcoholic beverages (54%) than non
      Aboriginal respondents (22%). Among the Aboriginal peoples who did drink alcohol,
      there were relatively more heavy drinkers (36%) compared with non-Aboriginal
      people (7%). There were more heavy drinkers among men than among women.
      CONCLUSION: Patterns of drinking habits vary between men and women and between
      Aboriginal and non-Aboriginal people. The majority of residents agree that
      alcohol is a problem in these communities. Unemployment, drug abuse, family
      violence, sexual abuse and racial discrimination are also believed to be
      important issues for the Bella Coola Valley. This information should be used to
      set priorities for future health and wellness programs.

PMID- 16454969
TI  - Review of salaried physician visits in a rural remote community - Bella Coola
      Valley.
AB  - INTRODUCTION: The current study quantifies visits to salaried physicians working
      in a geographically remote health care facility in British Columbia in 2001.
      METHODS: A retrospective chart review was conducted of patients residing in the
      Bella Coola Valley and attending the Bella Coola General Hospital/Medical Clinic
      (BCGH/Medical Clinic) in 2001. Visits to family physicians at this clinic, visits
      to the BCGH emergency department, hospital admissions, smoking rates and chronic
      disease prevalence rates were quantified. RESULTS: An estimated 2378 patients
      made 7747 BCGH/Medical Clinic family physician visits, and 4474 "other" visits in
      2001. These "other" visits included emergency department visits (n = 1736),
      hospital admissions (n = 245) and prescription visits (n = 2252). Twenty-six
      percent (n = 622) of the population did not see a family physician at all in
      2001, and 15% of the population accounted for 52% of all visits. Women had a
      higher number of visits than men; pregnant women had a higher number of visits
      than non-pregnant women, and the Aboriginal population saw family physicians more
      often than did non-Aboriginal people (p < 0.001). Those who had a chronic illness
      (e.g., diabetes) saw family physicians more frequently than did people who did
      not have that particular chronic illness (p < 0.01). The Aboriginal population
      used the BCGH/Medical Clinic and emergency department more frequently than did
      the non-Aboriginal population. BCGH/Medical Clinic physicians had an average of
      75 patient visits per week. An additional 22 "visits" per week were for writing
      prescription refills with the patient not present. CONCLUSION: Older people,
      people with chronic disease, women and Aboriginal peoples more frequently visited
      the family physicians. Salaried physicians working in geographically isolated
      communities appeared to behave in ways that minimized contact (e.g., used the
      phone, wrote prescriptions without patient being present) and maximized time
      efficiency for both themselves and their patients.

PMID- 16454970
TI  - Self-management of chronic conditions: implications for rural physicians of a
      demonstration project Down Under.
AB  - OBJECTIVES: This paper describes the outcomes achieved for clients of a
      demonstration project in self-management in one of Australia's most rural and
      remote states. METHODS: Client survey data obtained over a maximum of 18 months
      from 264 clients in 3 sites across Tasmania were analyzed using standard
      descriptive techniques. These data provided demographic information as well as
      client self-assessments of health and well-being, and health-related behaviours.
      Tests of significance were conducted on differences in client health data over a
      maximum of 4 data collection times. RESULTS: In relation to demographic factors,
      these data show low education, employment and income levels in an aged
      population. There were gender differences in project participation (many more
      females than males), and relatively low levels of completion of the self
      management course by those who were not married and who were living with their
      families. Statistically significant improvements in health dimensions were
      obtained for those clients attending the self-management course (where p values
      <.0.05): in the areas of distress, symptoms and depression. Data also show
      significant declines over time in client ratings of exercise behaviours and
      cognitive self-management strategies. CONCLUSIONS: The effects of barriers to
      self-management of chronic conditions (lack of formal education, age-related
      physical frailty, and poverty) are likely to be multiplied in areas showing a
      paucity of health professionals and related health infrastructure. The data for
      gender and living arrangements suggest the importance of tailoring self
      management programs to meet the needs of specific community sub-groups. Declining
      ratings are one of the least explored areas of self-management research, yet they
      point to the importance of sustaining interventions in rural communities. Rural
      physicians apprised of the issues in implementing successful self-management
      programs in rural contexts can be an important resource for more isolated
      communities wanting to achieve workable programs with sustainable gains.

PMID- 16454971
TI  - Surgical site infection rates at the Pontiac Health Care Centre, a rural
      community hospital.
AB  - INTRODUCTION: The prevalence of surgical site infections (SSIs) at the Pontiac
      Health Care Centre, a rural hospital, was compared with rates obtained by large
      multicentre studies. Postoperative nosocomial infection (NI) rates were also
      calculated. METHODS: A review of all surgical interventions involving an
      incision, excluding ophthalmological procedures, performed between October 2001
      and March 2003 (n = 831) was undertaken. Various clinical parameters were
      recorded. Infection rates were calculated. Data were analyzed using either the
      chi2 or Student's t test. RESULTS: The overall SSI rate was 5.54%: 3.50% in clean
      cases (C), 6.77% in clean-contaminated cases (CC), and 14.58% in contaminated or
      dirty cases (D). The postoperative NI rate was 6.62% (C, 3.68%; CC, 9.90%; D,
      16.67%). The mean duration of surgery was significantly higher among patients
      with SSIs and with NIs than those without infections for CC (133 +/- 95 v. 78 +/-
      60 min, p < 0.05, and 129 +/- 82 v. 77 +/- 60 min, p < 0.001 respectively) and D
      (130 +/- 96 v. 82 +/- 62 min, p < 0.001, and 136 +/- 92 v. 80 +/- 60 min, p <
      0.001 respectively). There were significantly higher SSI and NI rates among
      patients with combined American Society of Anesthesiologists (ASA) scores II and
      III than those with ASA score I in D (chi2 = 5.06 and chi2 = 6.34 respectively).
      There was also significantly higher SSI and NI rates among patients with combined
      Comorbidity Scale score 1-6 than those with no comorbid factors in CC (chi2 =
      4.14 and chi2 = 4.42 repectively) and D (not significant and chi2 = 4.04
      respectively). CONCLUSION: SSI rates at the Pontiac Health Care Centre were
      comparable to multicentre rates. Wound contamination category, type of surgery,
      duration of surgery, ASA score and Comorbidity Scale score were associated with
      SSI and NI rates. Studies have shown that examining NI rates decreases these
      rates by raising awareness; thus, we suggest that rural hospitals implement
      protocols to survey their postoperative NI rates.

PMID- 16454972
TI  - Country cardiograms case 29.

PMID- 16454973
TI  - Management of the occasional wrist ganglion.

PMID- 16454974
TI  - Potential role of Chinese medicinal herbs in the prevention of coronary artery
      restenosis.

PMID- 16454975
TI  - XS0601 reduces the incidence of restenosis: a prospective study of 335 patients
      undergoing percutaneous coronary intervention in China.
AB  - BACKGROUND: XS0601, consisting of active ingredients (Chuangxiongol and
      paeoniflorin), has been shown to inhibit arterial neointimal hyperplasia in
      animal models and in preliminary human studies. The objective of this study was
      to evaluate the safety and efficacy of XS0601 in preventing restenosis following
      percutaneous coronary intervention (PCI). METHODS: A multi-center, randomized,
      double-blind, placebo-controlled trial was conducted. A total of 335 patients
      were randomized into treatment with the oral administration of XS0601, or a
      placebo for 6 months after successful PCI. Angiographic follow-up was scheduled
      at 6 months, and clinical follow-ups performed at 1, 3 and 6 months after PCI.
      The primary end point was angiographic restenosis. The secondary end points were
      the combined incidence of death, target lesion nonfatal myocardial infarction,
      repeat angioplasty, and coronary artery bypass graft surgery. RESULTS: A total of
      308 patients (91.9%) completed the study and 145 cases (47.1%) received
      angiographic follow-up. The restenosis rates were significantly reduced in the
      XS0601 group as compared with the placebo group (26.0% vs. 47.2%, P < 0.05), and
      the minimum lumen diameter (MLD) was greater [(2.08 +/- 0.89) mm for XS0601 vs.
      (1.73 +/- 0.94) mm for placebo, P < 0.05]. XS0601 also significantly reduced the
      combined incidence of major adverse cardiac event (10.4% in the XS0601 group vs.
      22.7% in the placebo group, P < 0.05). The incidence of recurrent angina at 3 and
      6 months after PCI was also significantly reduced in XS0601 group (7.1% and
      11.0%) as compared with those in placebo group (19.5% and 42.9%) (P < 0.05). No
      significant side effects occurred within the 6-month follow-up period in the
      XS0601 group. CONCLUSION: Administration of XS0601 for 6 months is demonstrated
      to be safe and effective in reducing restenosis in post-PCI patients.

PMID- 16454976
TI  - Prognosis of unprotected left main coronary artery stenting and the factors
      affecting the outcomes in Chinese.
AB  - BACKGROUND: The long term prognosis of unprotected left main coronary artery
      (LMCA) stenting is controversial. This study was conducted to evaluate the
      immediate and long term outcomes of LMCA stenting in Chinese patients and to
      determine which factors affect the outcomes. METHODS: From May 1997 to March
      2003, 224 patients in 23 hospitals underwent elective unprotected LMCA stenting
      with bare metal stents. Their clinical records were analysed to ascertain
      immediate and long term outcomes of LMCA stenting as well as factors influencing
      the prognosis. RESULTS: Stents were implanted into LMCA successfully in 223 cases
      (99.6 %). One death (0.5%) and one case of non-Q wave nonfatal myocardial
      infarction (MI) occurred in hospital. The mean follow-up time was (15.6 +/- 12.3)
      months. Cardiac death developed in 10 cases (4.5%), noncardiac death in 2 cases
      (0.9%), nonfatal MI in 4 cases (1.8%), target lesion revascularization (TLR) of
      LMCA in 26 cases (11.7%) and TLR of nonLMCA in 37 cases (16.5%). Univariate
      analysis showed that cardiac death correlated with left ventricular ejection
      fraction (LVEF < 40%), female gender and LMCA combined with multivessel disease;
      that major adverse cardiac events (MACE) correlated with LVEF < 40%, bifurcation
      lesion and incomplete revascularization. Logistic regression analysis revealed
      that LVEF < 40% and female gender were independent predictors of cardiac death
      and MACE. Follow-up angiography was performed in 102 cases (45.7%). The
      restenosis rate was 31.4%. CONCLUSIONS: Long-term outcomes of stenting for
      selected patients with unprotected LMCA stenosis is acceptable. It should be
      performed in inoperable or low risk patients with LVEF > or = 40% and isolated
      LMCA disease or LMCA combined with multivessel diseases in whom complete
      revascularization can be obtained.

PMID- 16454977
TI  - Comparison of short- and mid-term outcomes between CYPHER and TAXUS stents in
      patients with complex lesions of the coronary arteries.
AB  - BACKGROUND: Drug-eluting stent (DES) could obviously reduce in-stent restenosis,
      which has been proved by international multi-center clinical trials. However, the
      types of the lesions for stenting were highly selected in these trials. Up to
      now, there has been no large scale study on the effect of DES in treating complex
      lesions in real world. Although REALITY trial was just reported during American
      College of Cardiology Congress 2005, the entry criteria for lesions were limited
      to one or two de novo lesions. This study was conducted to compare the short- and
      mid-term clinical outcomes between sirolimus-eluting stent (CYPHER stent) and
      paclitaxel-eluting stent (TAXUS stent) in patients with complex lesion. METHODS:
      This is a retrospective study. From April 2002 to June 2004, a total of 1061
      patients were treated with DES in Fu Wai Hospital, of which, 611 patients (642
      lesions with 698 CYPHER stents) were in CYPHER group, and 450 patients (534
      lesions with 600 TAXUS stents) were in TAXUS group. There was no significant
      difference in clinical data and lesion types between CYPHER group and TAXUS
      group. RESULTS: Success rates of stent implantation were 99.2% and 98.8% in
      CYPHER and TAXUS stent groups respectively. The major adverse cardiac events
      (MACE) during in-hospital and 6-8-month follow-up were 0.7% and 2.3% in CYPHER
      stent group versus 1.3% and 3.2% in TAXUS stent group. There was no significant
      difference in MACE rate between these two groups. Restenosis rate was a little
      higher in TAXUS stent group than that in CYPHER stent group (14.0% vs 7.3%), but
      there was no significant difference. The incidence of acute occlusion of side
      branch after implanting DES in main vessel was 6.9% in CYPHER group and 11.9% in
      TAXUS group (P < 0.05). CONCLUSIONS: CYPHER and TAXUS DES were safe and effective
      in patients with complex lesion. Clinical outcomes of CYPHER stent were better
      than TAXUS stent in bifurcation lesions. There was an increasing tendency in
      restenosis rate and late thrombosis in TAXUS group as compared with that of
      CYPHER group.

PMID- 16454978
TI  - Impact of Chinese guidelines for management of patients with acute myocardial
      infarction on outcomes of hospitalized patients.
AB  - BACKGROUND: The first Chinese guidelines for the diagnosis and management of
      patients with acute myocardial infarction (AMI) were issued by the Cardiovascular
      Branch of the Chinese Medical Association, the Editorial Board of the Chinese
      Journal of Cardiology, and the Editorial Board of the Chinese Circulation Journal
      in December 2001. However, it is still unclear whether these guidelines have
      produced a major impact on clinical practice and patient outcomes. The purpose of
      this study was to evaluate the impact of these guidelines on the management and
      prognosis of Chinese patients with AMI. METHODS: A retrospective study was
      carried out in patients with AMI who were admitted to Qilu Hospital of Shandong
      University from January 1994 to December 2004. Patients were divided into two
      groups: group A included patients admitted from January 1994 to December 2001,
      and group B comprised those admitted from January 2002 to December 2004.
      Therapeutic approaches and the occurrence rate of angina pectoris, reinfarction,
      heart failure and death during hospitalization were compared between two groups.
      RESULTS: A total of 1783 patients including 1208 cases in group A and 575 cases
      in group B were enrolled in this study. No significant difference was found in
      baseline characteristics between group A and group B patients (all P > 0.05).
      There were more patients undergoing reperfusion therapy within the first 24 hours
      after symptom onset in group B than in group A (35.8% vs 21.7%, P < 0.001).
      Administration of beta-blockers, angiotensin-converting-enzyme inhibitors
      (ACEIs), angiotensin receptor blockers (ARBs), statins, and heparins were more
      commonly seen in group B than in group A (P < 0.001). There were no significant
      differences in the use of nitrates or antiplatelet drugs between groups A and B
      (98.8% vs. 97.9%, P = 0.172, and 97.4% vs 98.6%, P = 0.113, respectively). In
      hospital angina pectoris, heart failure and death were all lower in group B than
      in group A (32.2% vs 41.2%, P < 0.001; 17.2% vs 26.2%, P < 0.001; and 6.4% vs
      9.4%, P = 0.038, respectively). There was no significant difference in the rate
      of reinfarction between group A and B patients (2.2% vs 1.7%, P = 0.492).
      CONCLUSIONS: Chinese guidelines for the management of patients with AMI issued in
      December 2001 resulted in changes in therapy that led to a significant
      improvement of in-hospital outcomes but not in the rate of reinfarction in
      patients with AMI.

PMID- 16454979
TI  - Effect of aspirin plus clopidogrel on inflammatory markers in patients with non
      ST-segment elevation acute coronary syndrome.
AB  - BACKGROUND: Aspirin can inhibit inflammatory reactions and platelet aggregation,
      but little is known about the effects of the combination of aspirin plus
      clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study
      was to determine whether aspirin plus clopidogrel can further suppress
      inflammation in patients with non-ST-segment elevation acute coronary syndrome
      (NSTEACS). METHODS: One hundred and fifteen patients with NSTEACS were randomized
      into two groups: group A (aspirin alone, n =58) and group B (aspirin plus
      clopidogrel, n =57). Patients in group A received a loading dose of 300 mg
      aspirin, then 100 mg per day. The patients in group B received a loading dose of
      300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel
      per day. Serum high sensitivity C-reactive protein (hs-CRP) and tumor necrosis
      factor-alpha (TNF-alpha) were measured in all patients at baseline prior to any
      drug treatment after admission, and at 7 and 30 days after beginning drug
      treatment. Thirty healthy volunteers on no medications were enrolled as controls
      (group C). RESULTS: Baseline levels of hs-CRP and TNF-alpha in group A and group
      B were significantly higher than those in group C. Seven days after
      administration, the levels of hs-CRP in both group A and group B decreased
      significantly [Group A: (6.15 +/- 1.39) mg/L vs (9.18 +/- 1.62) mg/L, P <0.01;
      Group B:(4.99 +/- 1.62) mg/L vs (10.29 +/- 1.47) mg/L, P <0.01]. Similarly,
      levels of TNF- alpha in both groups decreased at 7 days compared to baseline
      [Group A: (90.99 +/- 28.91) pg/ml vs (117.20 +/- 37.13) pg/ml, P <0.01; Group B:
      (74.32 +/- 21.83) pg/ml vs (115.27 +/- 32.11) pg/ml, P <0.01]. Thirty days after
      administration, the levels of hs-CRP in both group A and group B decreased
      further to (3.49 +/- 1.53) mg/L, and (2.40 +/- 1.17) mg/L respectively (P <0.01
      for both comparisons). Levels of TNF-alpha in groups A and B also decreased
      significantly between 7 and 30 days, to 63.28 +/- 29.01 pg/ml (group A) and
      (43.95 +/- 17.10) pg/ml (group B; P <0.01 for both comparisons). Significantly
      lower levels of hs-CRP and TNF-alpha were observed in group B compared to Group A
      at thirty days after initiating drug treatment (P <0.05). CONCLUSIONS: Aspirin
      plus clopidogrel treatment reduced levels of serum hs-CRP and TNF-alpha in
      patients with NSTEACS significantly more than aspirin alone. Because both aspirin
      and clopidogrel produce important anti-inflammatory effects, these results
      suggest the possibility that long-term treatment with aspirin plus clopidogrel
      may produce greater clinical benefits compared to treatment with aspirin alone.

PMID- 16454980
TI  - A new modification of transanal Soave pull-through procedure for Hirschsprung's
      disease.
AB  - BACKGROUND: One stage transanal Soave pull-through procedure (TSPP) is a recent
      popular operation in the treatment of Hirschsprung's disease (HD). With no
      visible scar and a short hospital stay, it is well accepted by surgeons and
      mothers. In the conventional Soave procedure, a long rectal muscular cuff left
      for anocolic anastomosis might increase the incidence of postoperative
      enterocolitis and constipation. This study presents a modified transanal Soave
      pull-through procedure (MTSPP) which includes an oblique mucosectomy and an
      oblique anastomosis with a short split muscular cuff. METHODS: A review of two
      groups of HD patients was made: 112 underwent conventional transanal Soave
      procedure from 1999 to 2001 (group 1) and 140 underwent modified transanal Soave
      procedure from 2002 to 2004 (group 2). A comparison was made between the two
      groups on operative data and postoperative complications. The data included: age
      at the operation, operating time, blood loss, time to feeds and hospital stay,
      occurrence of postoperative enterocolitis or constipation, need for anal
      dilatation, postoperative bowel function and perianal skin problems. RESULTS:
      There was no significant difference between two groups with respect to age,
      gender, length of colon resected, operating time, blood loss and hospital stay.
      However occurrence of postoperative enterocolitis, constipation, anastomotic
      stricture and time needed for anal dilatation were evidently less in group 2
      (MTSPP). The mean operating time in group 1 was (106 +/- 39) minutes with a range
      of 60 to 170 minutes; in group 2 was (101 +/- 36) minutes with a range of 66 to
      190 minutes. The average length of the bowel resected in group 1 was (24 +/- 7)
      cm, range 15 to 58 cm; in group 2 was (26 +/- 8) cm, range 15 to 70 cm. Two
      patients, one in each group, required laparoscopic assistance because of long
      aganglionic colon. Another patient in group 2 required laparotomy because of
      total colonic aganglionosis. Postoperative complications in group 1 included:
      temporary perianal excoriation in 34 patients (26 were < 3 months of age),
      enterocolitis in 21, anastomotic stricture in 11, recurrent constipation in 12,
      cuff abscess in 1, anastomosis leak in 1, soiling in 3 and rectal prolapse in 1.
      In group 2 post operative complications included: transient perianal excoriation
      in 37 patients (30 were < 3 months of age), enterocolitis in 13, anastomotic
      stricture in 5, recurrent constipation in 6, anastomotic leak in 1, adhesive
      bowel obstruction in 1 and soiling in 4. Complete bowel continence was found in
      97 children (86.6%) in group 1 and in 129 children (92.1%) in group 2 at one year
      followup after operation. CONCLUSIONS: Modified transanal Soave pull-through
      procedure for HD with oblique mucosectomy and anastomosis and a short split
      muscular cuff is a safe and feasible operation with low incidence of
      postoperative complication. It is an encouraging improvement of the conventional
      transanal Soave pull-through procedure. MTSPP is a preferable choice in the
      surgery of HD.

PMID- 16454981
TI  - Identification of Mycobacterium marinum 65 kD heat shock protein gene by
      polymerase chain reaction restriction analysis from lesions of swimming pool
      granuloma.
AB  - BACKGROUND: Nontuberculous mycobacterium (NTM) had been reported to cause
      cutaneous infections which are difficult to interpret due to the variability of
      the clinical manifestations. Among NTM infections, Mycobacterium marinum (M.
      marinum) are mostly seen to cause skin infection. It is therefore important to
      establish a rapid approach for detection and identification of M. marinum from
      lesions of patients with suspected M. marinum infections. METHODS: Specimens were
      obtained from 5 patients with swimming pool granuloma. DNA was extracted and
      polymerase chain reaction (PCR) was performed. PCR products were digested with
      Hae III and BstE II, then analysed by pattern restriction analysis to detect heat
      shock protein (hsp) 65 kD gene. RESULTS: The 65 kD hsp gene was found in all
      specimens from patients with swimming pool granuloma. PCR restriction analysis
      (PRA) identified all 5 samples to be M. marinum infections, and the result was
      consistent with that of routine bacteriological identification. The lesions
      subsided or markedly improved upon treatment. CONCLUSIONS: PRA is a sensitive,
      specific and rapid method in identification of mycobacteria. Application of this
      method will be helpful for early diagnosis of mycobacterial skin infections.

PMID- 16454982
TI  - Three novel FOXL2 gene mutations in Chinese patients with blepharophimosis-ptosis
      epicanthus inversus syndrome.

PMID- 16454983
TI  - The role of connective tissue growth factor, transforming growth factor beta1 and
      Smad signaling pathway in cornea wound healing.

PMID- 16454984
TI  - Efficacy and safety of gefitinib as monotherapy for Chinese patients with
      advanced non-small cell lung cancer.

PMID- 16454985
TI  - Percutaneous closure of huge patent ductus arterious associated with anomalous
      inferior vein cava drainage and dextrocardia with muscular ventricular septal
      defect occluder.

PMID- 16454986
TI  - Takotsubo syndrome with transient complete atrioventricular block.

PMID- 16454987
TI  - Multiple sclerosis after hepatitis B vaccination in a 16-year-old patient.

PMID- 16454988
TI  - A clinical classification of hypertension.

PMID- 16454989
TI  - Reoperations for occluded arterial bypasses in the lower limbs.
AB  - BACKGROUND: We reviewed the outcomes of reoperations for 29 patients (30 limbs)
      who had undergone occluded arterial bypass in the lower limbs from May 1996 to
      September 2005. METHODS: The 30 lower limbs of the 29 patients with
      arteriosclerotic obstruction received 44 reoperations, including thrombectomy
      alone (group T, 27) and inflow or outflow reconstruction plus thrombectomy (group
      C, 17). Among the 17 operations in group C, 17.6% (3/17) were inflow
      reconstructions involving the axillary-femoral (1), aorta-iliac (1) and aorta
      femoral (1) arteries, and 76.4% (13/17) outflow reconstructions involving the
      femoral-popliteal bypass-tibial (8), femoral-tibial (1), femoral-popliteal bypass
      popliteal arteries below the knee (2), and the femoral-popliteal bypass-tibial
      peroneal trunk (2). One patient (1 limb) underwent both inflow and outflow
      reconstructions with an iliac arterial stent and a graft-popliteal anastomosis
      patch. Polytetrafluoroethylene (PTFE) grafts were used in the inflow or outflow
      reconstructions above the knee. Autovenous grafts or autovenously combined PTFE
      grafts were used in the outflow reconstructions below the knee. RESULTS: The
      percentages of Fontaine stage III and IV before primary operation and reoperation
      were 60% (18/30) and 86.7% (26/30), respectively (P < 0.05). Four patients died
      of heart attack (2), stroke (1) and multiple organ failure (1) after
      reoperations. Among them, only 1 patient underwent occluded bypass, and others,
      patent bypass. Five patients after patent bypass are still alive. The
      accumulative patent rate was 28.6% (8/28). The average duration of patency in
      groups T and C was (4.16 +/- 5.68) (0.13 - 24) months and (7.14 +/- 6.37) (0.26 -
      21) months, respectively (P > 0.05). Among 42 reoperations, 19 failed within 1
      month in groups T (16) and C (3) (P < 0.01). Nine patients had limb amputated
      (10/28 limbs, 35.71%) because of graft infection (2 limbs), pseudo aneurysm at
      anastomosis (1 limb), and gangrene caused by failed grafts (7 limbs). The
      amputation was performed on 6 limbs within 1 month and on 4 limbs 1 month after
      reoperation (P > 0.05). The rate of limb salvage was 64.29% (18/28). CONCLUSIONS:
      The percentages of Fontaine stage III and IV before reoperation may be much
      higher than those before primary operation. Thrombectomy plus inflow/outflow
      reconstruction creates patency better than thrombectomy alone for re-occluded
      bypass.

PMID- 16454990
TI  - The influence of admission glucose on epicardial and microvascular flow after
      primary angioplasty.
AB  - BACKGROUND: Patients with elevated admission glucose levels may be at increased
      risk of death after myocardial infarction, independent of other baseline risk
      factors and more severe coronary artery disease. However, data regarding
      admission glucose and epicardial and microvascular flow after primary angioplasty
      is limited. METHODS: Angioplasty was performed in 308 ST-segment elevated
      myocardial infarction patients. Patients were divided into 3 groups on the basis
      of admission glucose level: group 1, < 7.8 mmol/L; group 2, (7.8 - 11.0) mmol/L;
      and group 3, >or= 11.0 mmol/L. RESULTS: Compared with group 1, patients in group
      2 and group 3 were more often female and older. Triglycerides (TG) in group 3
      were significantly higher than group 1. At angiography, they more frequently had
      2-vessel or 3-vessel disease. In the infarct-related artery, there was no
      relationship between hyperglycemia and thrombolysis in myocardial infarction
      (TIMI) 3 flow after percutaneous coronary intervention (PCI) (89.7%, 86.0% and
      86.3%, P = NS). However, corrected TIMI frame count (CTFC) in group 2 and group 3
      were more than group 1. TIMI myocardial perfusion grade (TMPG) 0 - 1 grade among
      patients with hyperglycemia after PCI were more frequent (30.9% and 29.0% vs
      17.3%, P < 0.05). There was less frequent complete ST - segment resolution (STR)
      and early T wave inversion among patients with hyperglycemia after PCI.
      CONCLUSION: Elevated admission glucose levels in ST - segment elevation
      myocardial infarction patients treated with primary PCI are independently
      associated with impaired microvascular flow. Abnormal microvascular flow may
      contribute at least in part to the poor outcomes observed in patients with
      elevated admission glucose.

PMID- 16454991
TI  - A novel CFTR mutation found in a Chinese patient with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is rare in Chinese. We investigated the
      mutations in the gene of cystic fibrosis transmembrane conductance regulator
      (CFTR) in a Chinese CF patient and reviewed the clinical features, gene mutations
      in Chinese CF cases. METHODS: Blood samples were collected from a previously
      reported CF girl and her parents. The 24 coding exons of CFTR of the proband were
      amplified and sequenced. RESULTS: A Chinese girl of 16 years old was diagnosed as
      CF at the age of 14. She had recurrent productive cough with bronchiectasis in
      bilateral upper lobes, parasinusitis and otitis media, but without pancreatic
      involvement. Her sweat chloride was (108.9 +/- 3.3) mmol/L. A heterozygous novel
      missense mutation of 699 C --> A which results in the amino acid change of N189K
      was identified in exon 5. In addition, a heterozygous 3821 - 3823 delT mutation
      in exon 19 was found in CFTR. The mutation 699C --> A was inherited from her
      father, and the 3821 - 3823 delT mutation was from her mother. Twenty patients
      with CF in Chinese reported from 1974 to 2004 were also reviewed. DelF508
      mutation was not found in the nine cases whose CFTR mutations were analyzed.
      CONCLUSIONS: The CF proband carries two heterozygous mutations (699C --> A and
      3821 - 3823 delT) in CFTR. 699C --> A mutation is a novel mutation which is not
      reported previously. Review of reported Chinese cases suggests that the genotype
      of Chinese CF may be different from those of white cases. More studies are needed
      to understand the spectra of CFTR and clinical CF features in Chinese.

PMID- 16454992
TI  - Biological properties of neural progenitor cells isolated from the hippocampus of
      adult cynomolgus monkeys.
AB  - BACKGROUND: The existence of neurogenesis in the hippocampus of adult nonhuman
      primates has been confirmed in recent years, however, the biological properties
      of adult neural stem cells or neural progenitor cells (NPCs) from this region
      remain to be extensively explored. The present work was to investigate on the
      expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the
      examination of their characteristics in vitro. METHODS: NPCs isolated from the
      hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free
      media containing growth factors, and were then allowed to differentiate by
      removing mitotic factors. The expansion capacity of NPCs and their
      differentiation potential were assayed by immunohistochemical and
      immunocytochemical analysis. RESULTS: During primary culture, NPCs underwent cell
      division, proliferation and aggregation to form neurospheres that were growing in
      suspension. Without mitotic stimulation, most neurospheres adhered to the culture
      dish and started to differentiate. Eventually, nearly 12% of the differentiated
      cells expressed neuron specific marker-beta III-tubulin (Tuj1) and 84% expressed
      astrocyte specific marker-fibrillary acidic protein (GFAP). In addition, the
      expression of a neural stem cell marker, nestin, was found both in NPCs and in
      the subgranular zone of adult monkey hippocampus, where NPCs were originally
      derived. CONCLUSIONS: NPCs from the hippocampus of adult cynomolgus monkeys can
      be expanded to some extent in vitro and are capable of differentiating into
      neurons and astrocytes. Further experiments to promote the in vitro proliferation
      capacity of NPCs will be required before adult NPCs can be used as a useful cell
      model for studying adult neurogenesis and cell replacement therapy using adult
      stem cells.

PMID- 16454993
TI  - The vascular endothelial growth factor expression and vascular regeneration in
      infarcted myocardium by skeletal muscle satellite cells.
AB  - BACKGROUND: Myocardial infarction results in tissue necrosis, leading to cell
      loss and ultimately to cardiac failure. Implantation of skeletal muscle satellite
      cells into the scar area may compensate for the cell loss and provides a new
      strategy for infarct therapy. Vascular endothelial growth factor (VEGF) is a
      promising reagent for inducing myocardial angiogenesis. Skeletal myoblast
      transplantation has been shown to improve cardiac function in chronic heart
      failure models by regenerating muscle. We hypothesized that VEGF expression and
      vascular regeneration increased in infarcted myocardium by skeletal muscle
      satellite cells, which can promote vascular producing and improve survival
      environment in infarcted myocardium. METHODS: The skeletal muscle satellite cells
      were implanted into the infarcted myocardium in a model through ligated left
      anterior artery in Louis Inbrad Strain rat. Specimens were got for identifying
      the expression of VEGF and the density of vascular by immunochemical method at
      two weeks after implantation. RESULTS: The proliferation and differentiation of
      the skeletal muscle satellite cell was very well. The expression of VEGF was
      higher in the implanted group (146.83 +/- 2.49) than that in the control group
      (134.26 +/- 6.84) (P < 0.05). The vascular density in the implanted group (13.00
      +/- 1.51) was also higher than that in the control (10.68 +/- 1.79) (P < 0.05).
      CONCLUSION: The implanted satellite cell could excrete growth factor that would
      induce angiogenesis and improve cell survival environment in infarcted
      myocardium.

PMID- 16454994
TI  - Signaling transduction pathways involved in basophil adhesion and histamine
      release.
AB  - BACKGROUND: Little is known about basophil with respect to the different
      signaling transduction pathways involved in spontaneous, cytokine or anti-IgE
      induced adhesion and how this compares to IgE-dependent and IgE-independent
      mediator secretion. The purpose of the present study was to investigate the roles
      of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol
      3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2
      in basophil adhesion and histamine release (HR). METHODS: Basophils (purity of
      10% - 50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies
      before used for adhesion study. Basophils were preincubated with the
      pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and
      HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was
      monitored using cell associated histamine as a basophil marker and the histamine
      was measured by the glass fiber assay. RESULTS: Basophil spontaneous adhesion to
      Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony
      stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18.
      Wortmannin at 1 micromol/L and PP1 at 20 micromol/L strongly interfered with,
      whereas PD98059 at 50 micromol/L weakly inhibited basophil spontaneous adhesion
      to Fn. One micromol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti
      IgE induced adhesion to BSA. PP1 at 20 micromol/L partly inhibited anti-IgE
      induced adhesion. Fifty micromol/L PD98059 marginally inhibited IL-5, weakly
      inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and
      PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose
      dependent manner. They inhibited calcium ionophore A23187 (10 micromol/L, 5
      micromol/L) induced basophil HR in a dose dependent manner, but to different
      extend with PP1 being the most efficient. CONCLUSIONS: Basophil spontaneous
      adhesion to Fn is mediated by beta1-integrins whereas cytokine induced adhesion
      to BSA is mediated by beta2-integrins. PI3K, src-kinases and ERK1/2 play distinct
      signaling roles in basophil adhesion and HR. PI3K is the key player while ERK1/2
      is the weakest participant.

PMID- 16454995
TI  - Humoral immune responses induced by anti-idiotypic antibody fusion protein of
      6B11scFv/hGM-CSF in BALB/c mice.
AB  - BACKGROUND: We have previously developed and characterized a monoclonal anti
      idiotype antibody, designated 6B11, which mimics an ovarian carcinoma associated
      antigen OC166 - 9 and whose corresponding monoclonal antibody is COC166 - 9
      (Ab1). In this study, we evaluate the humoral immune responses induced by the
      fusion protein 6B11 single-chain variable fragment (scFv)/human granulocyte
      macrophage colony-stimulating factor (hGM-CSF) and 6B11scFv in BALB/c mice.
      METHODS: The fusion protein 6B11scFv/hGM-CSF was constructed by fusing a
      recombinant single-chain variable fragment of 6B11scFv to GM-CSF. BALB/c mice
      were administrated by 6B11scFv/hGM-CSF and 6B11scFv, respectively. RESULTS: The
      fusion protein 6B11scFv/hGM-CSF retained binding to the anti-mouse F (ab) 2' and
      was also biologically active as measured by proliferation of human GM-CSF
      dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-CSF and
      6B11ScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to
      6B11scFv/hGM-CSF compared with the 6B11scFv alone. The level of Ab3 was the
      highest after the first week and maintained for five weeks after the last
      immunization. Another booster was given when the Ab3 titer descended, and it
      would reach to the high level in a week. CONCLUSION: The fusion protein
      6B11scFv/hGM-CSF can induce humoral immunity against ovarian carcinoma in vivo.
      We also provide the theoretical foundation for the application of the fusion
      protein 6B11scFv/hGM-CSF for active immunotherapy of ovarian cancer.

PMID- 16454996
TI  - Changes of learning, memory and levels of CaMKII, CaM mRNA, CREB mRNA in the
      hippocampus of chronic multiple-stressed rats.
AB  - BACKGROUND: The effect of chronic stress on cognitive functions has been one of
      the hot topic in neuroscience. But there has been much controversy over its
      mechanism. Such single stressor applied in the past could not simulate
      complicated living circumstances that people confronted with. The aim of this
      study was to investigate the effects of chronic multiple-stress on learning and
      memory as well as on the levels of calcium/calmodulin-dependent protein kinase II
      (CaMKII), calmodulin (CaM) mRNA, and cAMP-response element binding protein (CREB)
      mRNA in the hippocampus of rats. METHODS: The rats were divided randomly into
      stressed and control groups. The stressed group was given chronic multiple-stress
      for 6 weeks to set up a chronic multiple-stressed model. The rats' performance of
      spatial learning and memory was tested using Morris Water Maze (MWM) and Y-maze.
      Meanwhile, the expressions of CaMKII, CaM mRNA and CREB mRNA of rats' hippocampus
      were detected by immunohistochemistry, Western blot and reverse transcription
      polymerase chain reaction (RT-PCR), respectively. In addition, the width of
      synaptic cleft and the thickness of post-synaptic densities (PSD) were observed
      in the hippocampal CA3 region of rats by electron microscopy. RESULTS: After
      exposure to chronic multiple-stress for 6 weeks, the ability of learning and
      memory of the stressed group was higher than that of the control group (P < 0.05,
      P < 0.01). The width of synaptic cleft was smaller and the thickness of PSD was
      larger in the hippocampal CA3 region of the stressed group than in that of the
      control group (P < 0.01). The CaMK II immunostaining of the stressed group was
      stronger than that of the control group in the stratum radiatum and oriens of the
      hippocampal CA1 and CA3, especially in the stratum oriens. Quantitative analysis
      indicated that the expression of CaMK II, CaM mRNA, and CREB mRNA in the
      hippocampus of the stressed group was higher than that of the control group (P <
      0.05, P < 0.01). CONCLUSIONS: The capacity of learning and memory can be enhanced
      after chronic multiple-stress. The increased levels of CaMK II, CaM mRNA, and
      CREB mRNA may contribute to the enhancing effect of chronic multiple-stress on
      learning and memory.

PMID- 16454997
TI  - Assessment of prognosis and curative effect in patients with chronic severe
      hepatitis using the model for end-stage liver disease scores.

PMID- 16454998
TI  - Altered diaphragmatic contractile properties after high airway pressure
      controlled mechanical ventilation.

PMID- 16454999
TI  - Effects of respiratory syncytial virus infection on the airway neuronal
      plasticity and its relationship to the bronchial hyperresponsiveness in rats.

PMID- 16455000
TI  - CTX-M-14, CTX-M-24 and resistance in Escherichia coli and Klebsiella pneumoniae
      clinical isolates.

PMID- 16455001
TI  - One-year clinical outcomes of Chinese sirolimus-eluting stent in the treatment of
      unselected patients with coronary artery disease.

PMID- 16455002
TI  - Recurrent intracranial hemangiopericytoma with multiple metastases.

PMID- 16455003
TI  - Cardiac myxoma with glandular component: case report.

PMID- 16455004
TI  - Dual roles of apolipoprotein CI in the formation of atherogenic remnants.

PMID- 16455005
TI  - Aggressive low-density lipoprotein cholesterol lowering in secondary prevention
      of coronary heart disease.

PMID- 16455006
TI  - C-reactive protein levels and outcomes after statin therapy.

PMID- 16455007
TI  - Reduction in cardiovascular events with atorvastatin in type 2 diabetes.

PMID- 16455008
TI  - Aggressive versus moderate lipid-lowering therapy in hypercholesterolemic
      postmenopausal women.

PMID- 16455009
TI  - Should all diabetic patients receive statins?
AB  - Diabetes is known to play a causal role in promoting both microvascular and
      macrovascular complications. Reducing rates of end-organ damage has been a key
      objective of multiple clinical trials. In addition to the roles of glycemic and
      blood pressure control, it is evident that lipid reduction via statin therapy
      independently helps to reduce the risk of primary and secondary vascular events.
      This effect seems to remain intact across a broad range of lipid levels,
      suggesting additional mechanisms for efficacy of statin medications beyond
      cholesterol reduction. The demonstrated safety and data from recent trials lend
      support to the argument that all people with diabetes should be started on statin
      therapy regardless of their cholesterol level. It is also plausible that treating
      the underlying mechanisms of vascular dysfunction, inflammation, and injury so
      prevalent in diabetic patients would have similar implications for the patient
      identified as having insulin resistance or metabolic syndrome.

PMID- 16455010
TI  - Low-density lipoprotein reduction: is the risk worth the benefit?
AB  - Outcomes from recent lipid-lowering trials have led to an update of the third
      Report of the National Cholesterol Education Program (NCEP) Adult Treatment
      Panel's guidelines for treatment of hypercholesterolemia in adults. The updated
      NCEP guidelines now offer an optional goal of low-density lipoprotein (LDL)
      cholesterol of less than 70 mg/dL for high-risk individuals. Epidemiologic and
      clinical trial data suggest that for every 30-mg/dL change in LDL, the relative
      risk for coronary heart disease changes by about 30%. Statin therapy effectively
      lowers LDL and has an overall excellent safety profile in clinical trials.
      However, the use of high-dose statin therapy also entails greater risk of adverse
      events, such as myopathy and liver function test abnormalities, and this must be
      carefully weighed against the potential benefit for each patient. Alternative
      approaches targeting high-density lipoproteins and triglycerides may offer yet
      another option for coronary heart disease prevention in high-risk patients.

PMID- 16455011
TI  - Other than potency, are all statins the same?
AB  - Statins have been shown to interact with metabolic pathways that potentially
      affect physiologic functions beyond cholesterol balance. We may broadly
      categorize non-lipid effects of statins as clinically favorable or clinically
      detrimental. Whether non-lipid effects of statins are of clinical significance
      and whether there are differences in non-lipid effects among statins remain
      points of major current controversy. This review evaluates the available
      information on potential differences among statins in non-lipid effects.

PMID- 16455012
TI  - Dyslipidemia in special populations: Asian Indians, African Americans, and
      Hispanics.
AB  - Cardiovascular disease (CVD) is the leading cause of death in the United States,
      and certain population groups, such as South Asians, African Americans, and
      Hispanics, carry a disproportionately larger burden of CVD manifested as coronary
      artery disease, cerebrovascular disease, and hypertension. Persons of these
      special populations experience approximately two- to threefold greater morbidity
      and mortality. Prevalence of risk factors, including dyslipidemia, overweight,
      and diabetes, is not only higher in these groups, but is also rising. The reasons
      for such disparity appear to be multifactorial and influenced by such factors as
      lifestyle, diet, culture, genetics, and suboptimal healthcare. Furthermore,
      because these minority populations are not significantly represented in major
      clinical trials, evidence-based management strategies for treatment and
      prevention of CVD are seriously lacking. Lately, however, several randomized
      trials of therapy for dyslipidemia to reduce cardiovascular events among these
      ethnic groups have been undertaken. Preliminary data suggest the need for
      stricter goals and increasingly aggressive therapy for these special populations,
      including administrative and educational interventions.

PMID- 16455013
TI  - The effects of statins on high-density lipoproteins.
AB  - Statins inhibit cholesterol synthesis and are effective in lowering total
      cholesterol levels in plasma or serum due to reductions in low-density
      lipoprotein and very low-density lipoproteins, as well as reducing progression of
      coronary atherosclerosis, coronary heart disease, and stroke morbidity and
      mortality. These agents also modestly raise levels of high-density lipoprotein
      (HDL) cholesterol and its major protein, apolipoprotein (apo) A-I. The more
      effective statins can also raise the levels of large alpha-1 HDL particles as
      assessed by two-dimensional gel electrophoresis. High levels of these particles
      promote reverse cholesterol transport and protect against coronary heart disease
      and progression of coronary atherosclerosis. The mechanism whereby statins alter
      HDL and its subspecies appears to be due to reduction of triglyceride-rich
      lipoproteins, with a secondary decrease in cholesteryl ester transfer protein
      activity, and less transfer of HDL cholesterol to triglyceride-rich lipoprotein
      acceptor particles. Increasingly, statins will be combined with other agents such
      as ezetimibe, fibrates, niacin, and cholesteryl ester transfer protein inhibitors
      to optimize the entire lipoprotein profile to alter not only low-density
      lipoprotein, but also HDL, triglycerides, lipoprotein(a), and C-reactive protein,
      and also to reduce cardiovascular morbidity and mortality.

PMID- 16455014
TI  - Plant sterols are efficacious in lowering plasma cholesterol.

PMID- 16455015
TI  - Oxidized low-density lipoprotein biomarkers in atherosclerosis.
AB  - The concept that the oxidation of lipoproteins is central in the pathogenesis of
      atherosclerosis was first reported over 25 years ago, initially by in vitro
      studies and subsequently through experimental models of atherosclerosis. The
      innate immune system plays a key role in atherogenesis as manifested by its
      atherosclerosis-modulating properties, the immunogenicity of oxidized low-density
      lipoprotein (LDL), and the presence of oxidized LDL autoantibodies in plasma and
      lesions of humans. In the past 10 years it has been possible to generate
      monoclonal antibodies to oxidized LDL to directly measure oxidized LDL in plasma.
      This has led to a rapidly accelerating pace of new reports on the relationship of
      circulating oxidized LDL and various cardiovascular pathologic processes, which
      are the focus of this review.

PMID- 16455016
TI  - Serum amyloid A: the "other" inflammatory protein.
AB  - Inflammation long has been recognized as a hallmark of atherosclerotic lesions,
      but more recently attention has focused on chronic low-level elevations of
      specific plasma inflammatory proteins such as C-reactive protein (CRP) and serum
      amyloid A (SAA), which may not only represent markers of atherosclerosis risk but
      also participate directly in atherogenesis. This article briefly reviews evidence
      for and against potential roles of CRP as an atherosclerosis risk marker and in
      athero-genesis. The remainder of the article focuses on SAA, an inflammatory
      protein that is carried on, and may fundamentally alter the function of, high
      density lipoprotein. Data are reviewed regarding the regulation of SAA by dietary
      cholesterol, obesity, and insulin resistance, and its potential role as an
      atherosclerosis mediator. Lying at the intersection of inflammation,
      dyslipidemia, obesity, and insulin resistance, SAA may play a key role in
      regulating the contributions of these processes to atherogenesis.

PMID- 16455017
TI  - Endothelial cell heterogeneity and atherosclerosis.
AB  - Vascular diseases are the most common causes of morbidity and mortality in the
      Western world. These conditions, whether they involve small and/or large vessels,
      invariably manifest as localized lesions within the vascular tree. For example,
      atherosclerosis preferentially affects arteries at branch points, the outer wall
      of bifurcations, and the inner walls of curvatures. An important question is how
      systemic alterations in blood-borne factors (eg, those associated with cardiac
      risk factors) result in focal vasculopathy. A clue to the answer lies in the
      complex spatial and temporal dynamics of the endothelium. The goal of this review
      is to highlight concepts of endothelial cell heterogeneity and to apply these
      principles to an understanding of the pathogenesis, diagnosis, and treatment of
      atherosclerosis.

PMID- 16455019
TI  - Sentinel node dissection in vulvar cancer.
AB  - Vulvar cancer is an uncommon but devastating disease. In addition to radical
      vulvectomy, most patients require inguinofemoral lymphadenectomy, which often
      results in wound infection, wound breakdown, and chronic lymphedema. In the past,
      the gold standard for early lesions was radical vulvectomy with complete
      bilateral inguinal-femoral lymphadenectomy. This resulted in a low rate of
      recurrence but devastating disfigurement and high complication rates. Because
      only approximately 20% of patients with vulvar cancer have positive lymph nodes
      upon presentation, the traditional approach of inguinal-femoral lymphadenectomy
      for all patients resulted in many patients undergoing a morbid procedure without
      any real benefit. Sentinel node dissection, by removing only the nodes with the
      highest risk of containing metastases, offers a much less morbid alternative. In
      addition, because only one or two lymph nodes are removed, these can be subjected
      to a more thorough histopathologic analysis than conventional complete
      lymphadenectomy. This involves serial sectioning and immunohistochemical staining
      for cytokeratin antigen. Very small metastases, termed micrometastases, can be
      detected in this fashion. Therefore, sentinel node dissection with serial
      sectioning and immunohistochemical staining potentially offers a more accurate
      assessment of the regional nodes with less morbidity. Patients with positive
      sentinel nodes may then undergo additional therapy. Patients with negative
      sentinel nodes are theoretically at very low risk for metastases and should not
      require any additional treatment.

PMID- 16455018
TI  - Effective use of combination lipid therapy.
AB  - Despite the benefits of statin therapy, low-density lipoprotein (LDL) cholesterol
      management remains suboptimal and many patients do not achieve their recommended
      target goals. The aim of combination lipid drug therapy in high-risk patients is
      to achieve LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol
      goals with a minimum of serious adverse effects. Although statins are the drug of
      first choice, statin monotherapy may be limited by intolerance of dose escalation
      or failure to attain non-HDL cholesterol goals in those with mixed
      hyperlipidemia. Statins plus bile acid resins or ezetimibe can achieve greater
      than 50% reduction in LDL cholesterol, with little or no increase in adverse
      effects. Fibrates, niacin, and omega-3 fatty acids, when added to statins, can
      reduce triglycerides, increase HDL cholesterol, and reduce non-HDL cholesterol to
      a greater extent than statin monotherapy. The safety profile of combination lipid
      therapy is acceptable if the global coronary heart disease risk of the patient is
      high, thus producing a favorable risk to benefit ratio. Careful surveillance of
      hepatic transaminases, avoidance of gemfibrozil in statin-fibrate combinations,
      and awareness of statin-concomitant drug interactions is key to safe and
      efficacious use of combination lipid drug therapy.

PMID- 16455020
TI  - Transperitoneal laparoscopic pelvic and paraaortic lymphadenectomy in gynecologic
      cancers.
AB  - Laparoscopy, a minimally invasive surgery, may benefit select patients more than
      traditional abdominal approaches. The benefits of this procedure include low
      morbidity, shorter length of hospital stay, less blood loss, no significant
      increase in complications, and a shorter postoperative recovery period; this
      allows patients to begin adjuvant therapy more quickly. Laparoscopy has been used
      in gynecologic oncology since the early 1990s and has continued to grow and
      develop. Complex gynecologic oncology procedures can be performed with a low rate
      of complication and a low rate of conversion to laparotomy. The literature
      supports the fact that laparoscopy can be performed with short-term benefit with
      no increase in morbidity. Although the data are limited and emerging, the risk of
      cancer recurrence does not appear to increase because of this minimal access
      approach. Currently, advanced laparoscopic techniques are used to evaluate and
      treat cervical, endometrial, and ovarian malignancies. Specifically,
      transperitoneal laparoscopic lymphadenectomy including pelvic and paraaortic
      nodes is a feasible and efficacious procedure in the management of certain
      gynecologic malignancies.

PMID- 16455021
TI  - Ex vivo programmed cell death and the prediction of response to chemotherapy.
AB  - Since the earliest introduction of cytotoxic chemotherapy, investigators have
      pursued laboratory techniques designed to match patients to available drugs. Most
      of the work, published through the 1980s, reflected the prevailing view of cancer
      as a disease of dysregulated cell proliferation. Noteworthy, the description of
      apoptosis and programmed cell death, fundamental to our modern understanding of
      human tumor biology, did not occur until well after the heyday of in vitro
      chemosensitivity testing. By incorporating the modern tenets of carcinogenesis
      associated with perturbations in cell survival we can now re-examine laboratory
      assays of drug response in the context of drug-induced programmed cell death.
      Although there is interest in the use of genomic analyses for the prediction of
      chemotherapy response, the painful recognition that genotype does not equal
      phenotype will continue to limit broad application of these platforms.
      Biosystematics instructs that biological pathways rarely follow predicted routes.
      Efforts to force human biology to behave according to preconceived scientific
      dictates have proven costly and unsuccessful. Whole-cell experimental models with
      the capacity to evaluate all the operative mechanisms of cellular response to
      injury, acting in concert, provide valid tools for the study of human cancer.
      Educated by cellular behavior, we can expeditiously examine molecular processes
      of interest. This article briefly reviews the history of whole-cell experimental
      models of in vitro chemosensitivity testing then focuses on cell-death measures
      as the most robust predictors of clinical outcome in human cancer.

PMID- 16455022
TI  - Decompressive percutaneous gastrostomy tube use in gynecologic malignancies.
AB  - Percutaneous gastrostomy tube placement is a technically feasible and safe
      procedure for palliation in patients with small bowel obstruction (SBO) caused by
      advanced gynecologic malignancies. It is used commonly in patients who are poor
      surgical candidates, those who elect to not undergo surgery, and in patients with
      a limited lifespan because of end-stage cancer. Percutaneous gastrostomy tube
      placement is even technically possible in patients with tumor encasing the
      stomach, diffuse carcinomatosis, and ascites. Percutaneous endoscopic gastrostomy
      (PEG) tubes provide symptomatic relief of nausea and vomiting in most patients
      with advanced gynecologic cancer and SBO. PEG tube placement allows most patients
      to have end- of-life care at home or in an inpatient hospice. It is a cost
      effective procedure and is associated with low morbidity and mortality. Placement
      of PEG tubes should be highly considered in patients who present with recurrent
      bowel obstruction and who have undergone a prior operation for SBO in the setting
      of advanced gynecologic malignancy.

PMID- 16455023
TI  - Gene expression in breast cancer.
AB  - We now recognize that all breast cancers are not the same. Different
      characteristics in gene expression profiles result in differential clinical
      behavior. With the use of gene microarrays, different subtypes of breast cancer
      have been characterized. The basal subtype is characterized by high expression of
      keratins 5 and 17, laminin, and fatty acid-binding protein 7. The ERBB2+ subtype
      is characterized by high expression of genes in the ERBB2 amplicon. The luminal A
      subtype is characterized by the highest expression of the ER alpha gene. The
      luminal B and C subtypes have a lower expression of the ER cluster. The
      importance of these different subtypes lies in the fact that they differ in
      clinical outcome, with the basal and ERBB2+ subtypes having the worse prognosis
      and the luminal A group having the best prognosis. Different strategies for
      evaluating tumors in a clinical setting have been developed. Two such strategies
      are the 21-gene assay (Oncotype DX; Genomic Health, Redwood City, CA), which is
      currently in commercial use in the United States, and the 70-gene assay, which
      has been developed by a group in the Netherlands. These assays have been shown to
      predict clinical outcome and response to therapy. However, to date these gene
      assays have not been studied in a prospective manner. Over the next year,
      prospective clinical trials will be initiated using these predictive tools in the
      treatment of breast cancer. In the near future, clinical decisions will most
      likely be dictated by the genetic characteristics of the tumor, with the clinical
      characteristics becoming less important. Tailoring our treatment based on
      individual tumor characteristics will help us develop better therapeutic
      strategies and save many patients from receiving unnecessary toxic therapy.

PMID- 16455024
TI  - Issues related to choice of breast reconstruction in early-stage breast cancer.
AB  - Reconstructive surgeons focus their efforts on refining and developing techniques
      that optimize oncologic outcome and recreate the most natural breast mound
      possible. The introduction of perforator flaps offers the potential for faster
      and more complete recovery, while increasing technical complexity and the risks
      associated with microsurgical reconstruction. Despite appealing long-lasting
      results, autologous reconstruction is not the ideal reconstructive choice for
      every patient. Tissue/expander reconstruction can produce a satisfactory
      aesthetic outcome and is the reconstruction of choice for most women undergoing
      breast reconstruction. Immediate autologous reconstruction at the time of
      mastectomy best resembles the lost breast and favorably withstands radiation,
      compared with other reconstructive methods. However, the best method for
      integrating reconstruction and radiation is being actively debated. Placing a
      tissue expander at the time of mastectomy allows a skin-sparing approach and
      gives the patient a chance to see how she will feel with an implant. This
      approach avoids radiation damage to tissue reconstruction flaps, saving them for
      use later if necessary. This approach, using a tissue expander as a first step,
      is growing in popularity.

PMID- 16455027
TI  - [Use of a hybrid external fixator for treatment of tibial fractures].
AB  - PURPOSE OF THE STUDY: The study deals with treatment of the articular ends of the
      tibia, using a hybrid external fixator. A group of patients treated in the years
      2001-2003 is retrospectively evaluated. MATERIAL: Between 2001 and 2003, 21
      patients (16 men and 5 women) with a fracture of either the distal or the
      proximal end of the tibia were treated, using a Synthes external hybrid fixator,
      at the Department of Orthopedics and Traumatology, Faculty of Medicine, Charles
      University, Plzen. The average age of the patients was 49.2 years. The fractures,
      evaluated by the AO classification, included five type A3 fractures and 16 type
      C1 or C2 fractures. In 14 patients the fracture was associated with multiple
      trauma or polytrauma and in seven it was a single injury. Open fractures were
      treated in five patients (grade 2 in two and grade 3 in three patients), closed
      fractures in 16 patients (Type CII in 12 and type CIII in four patients, as
      assessed by Tscherne's classification). Fifteen patients had fracture of the
      proximal tibia and six had distal tibial fracture. A hybrid external fixator was
      used alone in six patients, and in combination with miniosteosynthesis in 15
      patients. METHODS: The first aim was to perform closed reduction or reduction
      from a minimal approach with an intraoperative image intensifier. Subsequently,
      the fracture was temporarily stabilized with pelvic reduction forceps or Ki wires
      and, if indicated, the articular ends were stabilized by miniosteosynthesis. When
      the outer ankle was fractured, plate osteosynthesis was carried out. Finally, a
      hybrid external fixator was applied. In the case of an open fracture, this
      procedure was preceded by soft tissue debridement. RESULTS: The evaluation, based
      on clinical and radiographic findings and subjective complaints of the patients,
      was made with the use of the Rasmussen and Bray scoring system. Nineteen patients
      were followed up, two failed to turn up. The results were excellent in five, very
      good in six, satisfactory in five and poor in three patients. Two repeat
      operations were necessary. DISCUSSION: The treatment of injury to the articular
      ends of the tibia, with the use of a hybrid external fixator, is one of the
      options for stabilization of both open and closed fractures. This method enables
      us to stabilize fractures of the tibial metaphysis as well as intra-articular
      fractures. Application of a hybrid external fixator is indicated in type A and
      type C fractures (AO classification). The state of crural soft tissues must be
      taken into consideration. The advantage of this method is the use of Kirschner
      wires, as fixation components, stretched in a circular frame. The fixation
      components require only minimum space for insertion in the metaphysis or
      epiphysis, the implant is stable and permits easy treatment of soft tissues.
      Another advantage is the possibility of early rehabilitation of the adjacent
      joints and loading of the extremity. Relatively frequent "pin infection" and
      therefore more frequent visits to the outpatient department can be considered a
      disadvantage. CONCLUSIONS: The method described here is, in addition to other
      options of fracture osteosynthesis, suitable for treatment of fractured ends of
      the tibia. External fixator application can be used with advantage for treatment
      of supra or infra-articular fractures of the tibia and fractures associated with
      marked swelling of soft tissues, for which internal osteosynthesis is not
      indicated, and in open fractures as well.

PMID- 16455025
TI  - The benefits and limitations of sentinel lymph node biopsy.
AB  - The status of the axilla is the single most important prognostic indicator of
      overall survival in patients with breast cancer. Staging is based on tumor size
      and on the presence of lymph node metastases. The number of lymph nodes, although
      prognostic, no longer impacts treatment options. Sentinel lymph node (SLN)
      mapping and dissection is a more sensitive and accurate technique for nodal
      evaluation and has been applied to staging of axillary lymph nodes in patients
      with breast cancer, providing prognostic information, with less surgical
      morbidity than with axillary lymph node dissection (ALND). When analyzed by an
      experienced pathologist with serial sectioning and immunohistochemical
      evaluation, SLN is the most accurate detection tool used in staging of breast
      cancer. In many centers that use these staging principles, ALND is no longer
      performed for histologically negative axillary SLNs. In addition, this technique
      may also be therapeutic because in most patients, the SLN is the only positive
      axillary node. SLN biopsy is justified in women with ductal carcinoma in situ who
      have a high risk of invasive carcinoma, such as those with large tumors, a mass,
      or high-grade lesions. SLN biopsy is performed in the setting of neoadjuvant
      chemotherapy and demonstrates accurate evaluation of the axilla in 90% of the
      cases. Women with locally advanced breast cancer may derive great benefit from a
      minimally invasive approach to the axilla because the extent of nodal involvement
      is unlikely to change further treatment. For clinically palpable nodes, ALND
      should be performed for therapeutic and local control. The use of sentinel node
      mapping in pregnancy is controversial. Vital blue dye is contraindicated in
      pregnant patients, although some have used radioactive colloid alone to map this
      subgroup of patients.

PMID- 16455026
TI  - Selection of optimal adjuvant endocrine therapy for early-stage breast cancer.
AB  - Oophorectomy was found to cause regression of advanced breast cancer toward the
      end of the 19th century. Decades later, the discovery that estrogen plays a
      central role in this process eventually led to two important consequences: first,
      different modalities were developed to suppress or antagonize estrogen; and
      second, the ability to detect estrogen receptor in breast cancer tissue became a
      predictor of response to treatment--probably the best marker for response among
      all solid tumors. Tamoxifen, which works by competitively antagonizing hormonal
      receptors in breast cancer cells, has been for the past three decades the
      standard of care for adjuvant therapy for any woman with hormone receptor
      positive early breast cancer, regardless of nodal status or menopausal setting.
      But as we strive to improve the utility of antagonizing or suppressing estrogen,
      new modalities are being developed. In the premenopausal setting, the advent of
      gonadotropin hormone-releasing hormone (also known as luteinizing hormone
      releasing hormone) analogues has allowed for medical and reversible suppression
      of ovarian function. This method has already been proven as effective as
      chemotherapy in preventing recurrence, and ongoing trials are aiming to better
      define its role in the adjuvant setting. In the postmenopausal setting, aromatase
      inhibitors (AIs) have revolutionized the adjuvant treatment of hormone-responsive
      cancers of all stages. The current standard of care has come to include AIs, as
      an alternative, in sequence, of after 5 years of tamoxifen. Ongoing research
      continues to develop agents to overcome hormonal therapy resistance.

PMID- 16455028
TI  - [Complications of internal fixation by a short proximal femoral nail].
AB  - PURPOSE OF THE STUDY: The article presents analysis of complications of the
      treatment of unstable fractures of the proximal femur by the proximal femoral
      nail (PFN Synthes). MATERIAL: Between October 1997 and October 2003, 239 patients
      were treated for unstable fractures of the proximal femur, 89 men and 150 women,
      average age 71 years. The minimum follow-up was 12 months. Unstable was
      considered a fracture in which it was impossible to restore by reduction the
      medial support -- the Adams' arch, i. e. the region below the lesser trochanter
      in subtrochanteric fractures. Prevailing in the group of patients were unstable
      pertrochanteric fractures (AO 31 A2.1, A2.2) that occurred in 55 % of patients,
      per-subtrochanteric fractures (AO 31 A2.3) accounted only for 26 % and
      subtrochanteric fractures (AO 31 A3.3) for 19 %. RESULTS: The fracture healed in
      95 % of patients within 6 months and in 98 % of patients within 9 months. There
      were 29 intraoperative complications recorded in 19 patients (12 %). This
      category included also intraoperative technical difficulties. Only 9 patients (4
      %) were reoperated on. Early postoperative complications occurred in 16 patients
      (8 %) requiring reoperation in 7 cases. Six late postoperative complications
      occurred in 3 patients. DISCUSSION: Intramedullary implants for internal fixation
      of the proximal femur tolerate higher static and several times higher cyclical
      loading as compared to DHS types of implant. As a result the fracture heals even
      without the primary restoration of the medial support. The implant temporarily
      compensates the function of the medial column. When this function is not restored
      in a limited period of time, the internal fixation, although correctly performed,
      fails. The main cause of complications are technical mistakes or failure to
      observe the proper surgical technique. CONCLUSION: The most frequent mistake is
      reduction with the persisting varus position or distraction in the fracture line,
      incorrect placement of the screw in the femoral neck or the nail in the femoral
      shaft, wrong choice of the length of the screws, unnecessary hesitation in
      solving the defect in the course of the treatment. Forced insertion of the
      implant may cause additional damages to the skeleton. PFN is a quality implant
      for the treatment of unstable pertrochanteric and subtrochanteric fractures of
      the femur. The number and severity of complications may be reduced by the
      observance of proper principles of reduction and exact surgical technique.

PMID- 16455029
TI  - [Metaphyseal fibrous defect].
AB  - PURPOSE OF THE STUDY: The aim of the study was to identify predisposition to the
      development of metaphyseal fibrous defect (MFD) on the skeleton and to select
      appropriate imaging methods and examination for detection of atypically located
      or larger cortical lesions. MATERIAL: A group of 38 randomly selected patients
      with MFD was analyzed. It comprised of 27 boys and 11 girls at average ages of
      13.7 years and 15.5 years, respectively. The youngest child was 4 and the oldest
      patient was 30 years old. METHODS: Thirty-two patients with a history of trauma
      and six patients with problems associated with sports activities were examined by
      plain radiography. Additional examination included CT scans in eight, MRI in two,
      scintigraphy in 17, angiography in seven and genetic examination in three
      patients. Histological evaluation confirming the presence of MFD was carried out
      in seven patients. RESULTS: The majority of lesions (75.6 %) were found around
      the knee, 17 in the distal femur and 17 in the proximal tibia. Eight lesions
      (17.8 %) were present in the distal tibia and three (6.6 %) were at other sites.
      Multifocal lesions, when detected, were associated with von Recklinghausen's
      neurofibromatosis, Marfan's disease or familiar occurrence. In most cases the
      diagnosis was made on the basis of plain radiographic findings. For large lesion
      in atypical locations, examination by CT, MRI, scintigraphy or biopsy were
      recommended. DISCUSSION: In this section the authors discussed other pathologic
      conditions that must be distinguished from MFD. CONCLUSIONS: The bones around the
      knee were affected most often. Multifocal MFD lesions were associated with von
      Recklinghausen's neurofibromatosis, Marfan's disease or familiar occurrence. The
      diagnosis was usually based on plain X-ray examination. To diagnose atypical and
      large lesions, advanced imaging (CT, MRI), scintigraphy or biopsy were
      recommended.

PMID- 16455030
TI  - [Varus supracondylar osteotomy of the femur -- long-term results].
AB  - PURPOSE OF THE STUDY: Varus supracondylar osteotomy of the femur is the surgical
      procedure indicated in young patients with symptomatic unicompartmental
      gonarthrosis associated with a valgus knee deformity. The aim of the study was to
      evaluate long-term results and to draw attention to the most frequent mistakes in
      the indication and surgical technique. MATERIAL: In the period from 1985 to 1995,
      35 knees in 33 patients were treated by varus supracondylar osteotomy of the
      femur in the Department of Orthopedics, Teaching Hospital, Faculty of Medicine,
      Palacky University in Olomouc. The technique of medial closing wedge osteotomy of
      the distal femur held with a 90 degrees plate was used. For post-operative
      immobilization, a brace was applied in most of the patients. METHODS: The
      information recorded was as follows: age, type of arthritis, follow-up period,
      preoperative tibio-femoral angle, postoperative tibio-femoral angle, range of
      motion before and after surgery, post-operative Knee Society scores,
      complications, number of osteotomies converted to total knee arthroplasty, and
      time between osteotomy and knee prosthesis implantation. The survival of
      osteotomy was evaluated by the Kaplan-Meier analysis for censored data. The
      change in parameters obtained before and after surgery was assessed by the one
      sample t-test and non-parametric Wilcoxon test. RESULTS: All 35 knees were
      evaluated. The average Knee Society score at follow-up was 77 points (range, 61
      95), the average functional knee score was 78 points (range, 61-95). The average
      range of motion increased from the pre-operative 112 degrees (range, 75-130
      degrees ) to post-operative 115 degrees (range, 90-135). This difference was
      statistically significant (p = 0.032; t-test for paired samples; Wilcoxon test).
      The average follow-up was 14.7 years (range, 10-20 years). The most frequent
      complications were progression of medial compartment arthritis (8 knees), loss of
      correction (6 knees) and arthrofibrosis (5 knees). Osteosynthesis failed in two
      knees and, in two, superficial wound infection was recorded. Due to failure of
      osteotomy, six patients (17 %) subsequently underwent total knee replacement. The
      osteotomy survival rate was 95% at 18 years (CI, 16-19 years). DISCUSSION: The
      results of this study are based on long-term observation and can be compared with
      the studies by Mironneau et al. or Finkelstein et al. These and other authors
      have achieved better results in terms of score values, which can be explained by
      the following five factors: the follow-up in their studies was significantly
      shorter than in our study. At our department knee arthroplasty became a routine
      surgical technique as late as the early 1990s, and even after that some tendency
      continued to indicate bi- and tri-compartmental osteoarthritis for osteotomy.
      Also we operated on patients who were overweight and on those who were older than
      recommended for this procedure. CONCLUSIONS: The prerequisite for successful
      varus supracondylar osteotomy of the femur in unicompartmental gonarthrosis is
      that the patient is active, younger than 62 years and is not overweight. Early
      diagnosis followed by osteotomy, which prevents further progression of the
      disease, is also important. The detailed pre-operative planning and exact
      performance of the procedure are fundamental conditions. In the post-operative
      period it is necessary to observe the relevant regimen including rehabilitation
      therapy. When these conditions are fulfilled, osteotomy can markedly postpone the
      necessity of total knee arthroplasty.

PMID- 16455031
TI  - [Rupture of the pectoralis major muscle -- causes, diagnosis, treatment].
AB  - PURPOSE OF THE STUDY: Between 01/02 and 01/03 four cases of ruptures of the
      pectoralis major muscle were treated in our hospital by suture. The data were
      retrospectively analysed, all patients underwent a follow up examination. We
      compared our results with the literature found by internet search. PATIENTS AND
      METHODS: Between 01/02 and 01/03 four male patients with a rupture of the
      pectoralis major muscle (PM) were treated surgically by suture. Three of them had
      an acute rupture (75%), in one case the injury was older (25%). In three cases
      patients underwent MRI examination. All patients were examined for a follow up by
      the Constant score and the score of McEntire. RESULTS: The median age of the
      patients was 36.5 (min: 27; max: 51) years; in three cases the left side was
      injured, in one case the right. All cases of the acute injury happened during
      weight bearing. The older rupture (1.5 years ago) was caused by a motorcycle
      accident. The follow up examination was performed after 8.5 (min: 7; max: 13)
      months. According to the score of McEntire the functional and clinical result was
      in all cases good to very good. The median value of the Constant score on the
      injured side was 90 (min: 63; max: 96) compared to 99 (min: 95; max: 100) on the
      other side. CONCLUSION: The rupture of the pectoralis major muscle is a rare
      entity and appears in young male patients. The most common reason for this injury
      is weight bearing or physical exercises, often in combination with anabolic
      steroids. Clinical and functional results after suture are good; patients
      normally reach the former level of activity and are able to practice their sports
      in the same way like they did before the trauma. According to our experiences, we
      recommend the surgical therapy.

PMID- 16455032
TI  - Quantification of changes in graft dimension after corrective osteotomy of the
      distal end of the radius.
AB  - PURPOSE OF THE STUDY: This is a cross section retrospective study which shows
      undertaken in order to determine the frequency and degree of postoperative
      alterations in size of cortico-cancellous autografts used in corrective
      osteotomies of the distal radius. PATIENTS AND METHOD: In the period from 1987 to
      2002, 50 patients (21 females and 29 males, mean age 38 years, range 18-64, were
      treated with corrective osteotomy, bone grafting and internal fixation after mal
      united Colles' fracture. The patients were followed up from 6 months to 5 years
      (average 15 months). Heights of volar, ulnar, dorsal and radial sides of the
      graft were determined from radiographs (preoperative, immediately after the
      surgery and at the late follow-up examination) according to the BIZCAD method and
      put into the computer program, which compared them in three dimensions. RESULTS:
      In sixteen patients (32 %) one or more sides of the graft decreased in height
      during the postoperative period by more than three millimeters. In five cases
      there was a complete resorption of the implanted graft. In the other thirty-four
      cases, an average decrease in all sides of graft was statistically significant.
      Unequal decrease led to an increase of volar inclination angle of the distal
      articular surface of the radius, averaging 3 degrees. Influence of age on the
      diminution of the graft size was found. More distally placed grafts had less
      incidence of significant resorption. A correlation between initial height of the
      side of the graft and its alterations was also found (r=0.49, p<0.001).
      CONCLUSION: Postoperative changes in the size of graft are frequent and represent
      a serious obstacle to the success of corrective osteotomies. We recommend that:
      1. the use of a the higher bone graft for elongating of the radius, however with
      a greater chance of resorption; the alternative method of ulna shortening should
      be considered; 2. the osteotomy line and the grafts should be placed more
      distally to decrease the risk of resorption; 3. if osteotomy can't be performed
      distally enough, postoperative immobilization for about three weeks should be
      considered.

PMID- 16455033
TI  - [Our experience with repair of the scapholunate ligament using the MITEK bone
      anchor].
AB  - PURPOSE OF THE STUDY: A complete rupture of the scapholunate (SL) interosseal
      ligament results in palmar flexion of the scaphoid and dorsiflexion of the lunate
      that leads to disintegration of the carpal circle and the development of
      scapholunate dissociation with dorsal intercalary segment instability. If the
      injury is not treated properly or early, the abnormal position of the scaphoid
      and lunate results in degenerative changes of the wrist shown by X-ray and
      referred to as scapholunate advanced collapse (SLAC). The aim of this study was
      to evaluate the results of our method used for reconstruction of the SL ligament
      by means of MITEK bone anchors in acute injury. MATERIAL AND METHODS: The group
      included 17 patients, 12 male and 5 female, aged 18 to 49 years, with complete SL
      ligament ruptures. The dominant hand was affected in 10 patients. After the
      diagnosis had been confirmed, we performed reconstructive surgery involving re
      attachment of the SL ligament to the scaphoid by means of the MITEK Mini G2
      anchor. The patients were examined by X-rays at 3, 6, 12 and 24 months after the
      operation to assess the SL angle, capitolunate (CL) angle, SL distance and signs
      of SLAC. Hand function and pain were evaluated on the basis of the Wrightington
      Hospital Wrist Scoring (WHWS) system. RESULTS: The average preoperative value of
      the SL angle was 79 degrees and was corrected to 38 degrees by surgery. By
      subsequent physical therapy for 12 months, an SL angle of 51 degrees was achieved
      and increased to 52 degrees during the following year. The CL angle, showing a
      preoperative average value of 34 degrees, was corrected by surgery to 6 degrees,
      further increased to 9 degrees by exercising and then remained unchanged. The
      average SL distance of 5.25 mm preoperatively was reduced to 2.75 mm by surgery
      with no further change. At 24 months of follow-up, the results of pain evaluation
      were excellent, good and satisfactory in 41 %, 47 % and 12 % of the patients,
      respectively, with no poor outcome indicating restriction of the patient's daily
      activities. Functioning of the hand was excellent in 47 %, good also in 47 % and
      satisfactory in 6 % of the patients. The range of motion was excellent, good and
      satisfactory in 24 %, 64 % and 12 % of the patients, respectively. No stiff wrist
      was recorded after reconstruction of the SL ligament by our method. The hand grip
      was evaluated as excellent in 47 %, good in 35 % and satisfactory in 18 % of the
      patients. DISCUSSION: The results show that by reconstruction of the SL ligament
      with the use of MITEK anchors, radiographic values of the SL and CL angles and SL
      distance can reach the normal levels within 24 months of the operation. As
      assessed by the WHWS system, excellent and good results were achieved in 88 % of
      the wrists treated. Similarly, at 24 months of followup, excellent or good
      functional outcomes were reported by 94 % of the patients, and excellent or good
      results in relation to the range of motion and hand grip were experienced by 88 %
      and 82 % of the patients, respectively. CONCLUSIONS: When treating complete SL
      ligament ruptures within 4 weeks of injury, stabilization with Kirschner's wires,
      re-attachment of the SL ligament and suture of the articular capsule are adequate
      procedures leading to the best results. The ligament reconstruction with MITEK
      anchors, as presented here, is a relatively simple method giving good results.
      For treatment of chronic instability it is necessary to use other surgical
      procedures that, however, will reduce wrist mobility to a greater extent.

PMID- 16455034
TI  - [Purulent arthritis of the spinal facet joint].
AB  - Purulent arthritis of the facet joint is a rare affection. It occurs most
      commonly by hematogenous spread of microorganisms and the initiating agent is in
      most cases Staphylococcus aureus. Diagnosis is made predominantly by means of MRI
      and hemocultures, or culture of pus aspirated from the abscess with a needle.
      Conservative therapy consists in a long-term administration of antibiotics. In
      case of insufficient response to the treatment or development of a neurological
      deficit, the patient is indicated for surgical revision, drainage and, if
      necessary, for decompression of nerve structures. In addition to sepsis, a severe
      complication of the purulent arthritis of the facet joint is propagation of the
      abscess epidurally, intradurally or foraminally with the risk of the onset of
      neurological deficit. In their case series the authors present four cases of
      purulent arthritis of the facet joint diagnosed and treated at the Department of
      Spinal Surgery of the University Hospital in Motol, Prague.

PMID- 16455035
TI  - Spectrophotometric estimation of functional groups on microslides for preparation
      of biochips.
AB  - A universal reagent 1-O-(4,4'-dimethoxytrityl)-6-aminohexanol (DTAH) is described
      for the estimation of surface-bound functionalities (epoxy, aldehyde, and
      carboxyl) required for preparation of oligonucleotide arrays (biochips). The
      method involves the reaction of universal reagent DTAH with surface-bound
      functionality under microwaves for 10 min, followed by washings to remove the
      excess reagent. In the subsequent step, a weighed amount of DTAH-treated surface
      is exposed to acid to liberate 4,4'-dimethoxytrityl cation, which is measured at
      505 nm to determine the functional group loading on the surface.

PMID- 16455036
TI  - Two-dimensional strandness-dependent electrophoresis: a method to characterize
      single-stranded DNA, double-stranded DNA, and RNA-DNA hybrids in complex samples.
AB  - We describe two-dimensional strandness-dependent electrophoresis (2D-SDE) for
      quantification and length distribution analysis of single-stranded (ss) DNA
      fragments, double-stranded (ds) DNA fragments, RNA-DNA hybrids, and nicked DNA
      fragments in complex samples. In the first dimension nucleic acid molecules are
      separated based on strandness and length in the presence of 7 M urea. After the
      first-dimension electrophoresis all nucleic acid fragments are heat denatured in
      the gel. During the second-dimension electrophoresis all nucleic acid fragments
      are single-stranded and migrate according to length. 2D-SDE takes about 90 min
      and requires only basic skills and equipment. We show that 2D-SDE has many
      applications in analyzing complex nucleic acid samples including (1) estimation
      of renaturation efficiency and kinetics, (2) monitoring cDNA synthesis, (3)
      detection of nicked DNA fragments, and (4) estimation of quality and in vitro
      damage of nucleic acid samples. Results from 2D-SDE should be useful to validate
      techniques such as complex polymerase chain reaction, subtractive hybridization,
      cDNA synthesis, cDNA normalization, and microarray analysis. 2D-SDE could also be
      used, e.g., to characterize biological nucleic acid samples. Information obtained
      with 2D-SDE cannot be readily obtained with other methods. 2D-SDE can be used for
      preparative isolation of ssDNA fragments, dsDNA fragments, and RNA-DNA hybrids.

PMID- 16455037
TI  - A simple hybridoma screening method for high-affinity monoclonal antibodies using
      the signal ratio obtained from time-resolved fluorescence assay.
AB  - In hybridoma screening, quantitative kinetic evaluation is difficult since the
      concentration of each antibody in the hybridoma supernatant is unknown. From
      modeling calculations, we hypothesized that the ratio of two different antigen
      antibody concentrations might allow discrimination of high-affinity monoclonal
      antibodies irrespective of the antibody concentration. Using anti-alpha
      fetoprotein monoclonal antibodies of known affinity, we set the signal ratio of a
      time-resolved assay at >0.1, in which the antigen concentrations were 10 and 100
      ng/mL. From anti-alpha-fetoprotein hybridoma screening with this assay, it was
      possible to effectively select high-affinity monoclonal antibodies with KD values
      below 1x10(-8) M. High-sensitivity sandwich enzyme-linked immunosorbent assay
      which detects domain III of alpha-fetoprotein has been established using selected
      high-affinity monoclonal antibodies. This screening method is useful for
      selection of high-affinity monoclonal antibodies of potential diagnostic value.

PMID- 16455038
TI  - Fabrication of an antibody microwell array with self-adhering antibody binding
      protein.
AB  - One of the promising methods of preparing antibody arrays is immobilizing
      antibodies with protein A or protein G, each of which binds specifically to the
      heavy chain constant (Fc) region of immunoglobulin G (IgG). In this system,
      antibody immobilization efficiency depends on the number of active Fc binding
      proteins that need to be immobilized on the surface. Here we have designed and
      constructed an Fc binding protein with a self-adhering ability that can be
      immobilized on the hydrophobic surface by simple adsorption. It consists of an Fc
      binding domain of protein G (G3) and hydrophobic domain of elastin (E72). Direct
      observation revealed its self-adhering ability on the hydrophobic surface. The
      enzyme-linked immunosorbent assay (ELISA) showed that it retained antibody
      binding ability on the surface. The antibody array model was prepared on a
      hydrophobic microwell glass slide with E72G3, which specifically detect the
      antigen with a sevenfold greater sensitivity than the G3-treated slide. These
      results suggest that the E72G3 is useful for simple and effective immobilization
      of antibodies and can be used to fabricate any immuno devices.

PMID- 16455039
TI  - Development of quartz-crystal-microbalance-based immunosensor array for clinical
      immunophenotyping of acute leukemias.
AB  - An integrated piezoelectric immunosensor array has been developed to
      immunophenotype acute leukemias in clinic. Each quartz crystal microbalance (QCM)
      was fabricated with plasma-polymerized film of n-butylamine, nanogold particles,
      and protein A (PA) to be used to immobilize antibodies in orientation. Leukemic
      lineage-associated monoclonal antibodies were separately immobilized onto the
      nanogold-PA-modified surface of the crystals, which were constructed by a 2 x 2
      type of probes forming a QCM-based immunosensor array. The main detection
      conditions were investigated, including the immobilization amount of antibodies,
      pH, immunoreaction time, sample dilution ratio, etc. The immunophenotyping
      feasibility of the new technique was investigated through simultaneously
      analyzing Jurkat cells by the immunosensor array method, immunohistochemistry,
      and flow cytometry. It was found that the developed technique could readily
      identify leukemia samples in 5 min and might monitor dynamically the
      immunoreaction processes. Moreover, comparison studies were carried out for CD
      antigens expressed on the nucleated cells isolated from 96 acute leukemic
      patients and 24 normal subjects using the QCM-based immunosensor method and the
      fluoroimmunoassay. Results obtained by immunophenotyping patients' samples with
      the immunosensor-based method achieved the rate of 88.93% in 768 groups of
      numerical data, where no significant statistical difference was observed between
      the two methods when checked by chi2 analysis (chi2 = 3.4, p > 0.05). This new
      immunosensor array showed the merits of high sensitivity, high specificity, good
      reproducibility, easy operation, and low cost. The results of specimen evaluation
      indicated that it might be clinically suitable for quantifying human
      differentiated leukocytes and immunophenotyping of acute leukemias.

PMID- 16455040
TI  - [Primary biliary peritonitis].
AB  - PURPOSE: The purpose of this study was to debate the epidemiologic and clinical
      features of primitive biliary peritonitis (PBP) as much as a rare pathology; and
      especially to obtain a more comprehensive view of factors associated with a
      severe prognosis. METHOD: It is a retrospective survey of 15 patients, collected
      from 2000 to 2003. Only primitive biliary peritonitis has been included. RESULT:
      It is a series of 15 patients, 6 men and 9 women, with a mean age of 62 years.
      Biliary lithiasis was incriminated in 14 cases. Clinical picture was an acute
      peritonitis in every case. Six patients were operated on by median incision, the
      others by costal one. The death rate is of 26,6%, all death were a direct
      complication of PBP. Factors associated with a higher mortality are an IGS II
      score superior or equal than 31 and a number of organ failures superior or equal
      to 3. CONCLUSION: PBP is a rare and severe pathology that concerns aged women.
      Biliary lithiasis is the main etiology. Treatment is essentially surgical, in
      association with active per-operative resuscitation.

PMID- 16455041
TI  - [Abecedary of the "Annales". Part 13].
AB  - The terms included and detailed in the present part are: incidence, confidence
      interval, interquartile interval, kappa value.

PMID- 16455042
TI  - Localization of a long-chain acyl-CoA hydrolase in spermatogenic cells in mice.
AB  - Brain acyl-CoA hydrolase (BACH) hydrolyzes long-chain acyl-CoAs to free fatty
      acids and CoA-SH. BACH is highly distributed in brain and is localized in
      neurons, but not glial cells. This suggests that BACH plays a specific role in
      neurons. BACH is also detected in testis, although the expression profile of BACH
      is unknown in testis. In this study, developmental changes and cellular
      distribution of BACH were examined in mouse testis. Before postnatal day (P) 10,
      BACH was detected at very low levels by Western blotting. Then, BACH content
      rapidly increased from P14 and reached maximum levels at P21, remaining high
      until at least P70. The increase in BACH content corresponded to the appearance
      of pachytene spermatocytes, which was confirmed by immunohistochemistry. BACH was
      also detectable in spermatids, but not in spermatogonia, mature spermatozoa.
      These results suggest that BACH is expressed in a cell-specific manner and plays
      a role in spermatogenesis.

PMID- 16455043
TI  - Involvement of phosphatidylinositol 3-kinase and extracellular-regulated kinase
      in hepatic stellate cell antioxidant response and myofibroblastic
      transdifferentiation.
AB  - Liver fibrogenesis is dependent upon transdifferentiation of hepatic stellate
      cells to a profibrogenic phenotype. Prooxidant stress purportedly stimulates both
      an antioxidant response and myofibroblastic transdifferentiation with fibrogenic
      gene expression; however, mechanisms by which oxidative stress mediates stellate
      cell activation remain unclear. To this end, stellate cells were treated with
      tert-butylhydroquinone (tBHQ), a known inducer of antioxidant response genes. As
      anticipated, tBHQ induced expression of antioxidant response element (ARE)
      regulated genes via the transcription factor Nrf2. Further, tBHQ promoted
      transdifferentiation of quiescent stellate cells cultured on Engelbreth-Holm
      Swarm extracellular matrix. Pretreatment of cultured stellate cells with a
      phosphatidylinositol 3-kinase (PI3K) inhibitor blocked tBHQ-mediated ARE
      dependent gene induction as well as stellate cell transdifferentiation. In
      contrast, extracellular signal-regulated kinase, which was demonstrated to be
      prominently phosphorylated following tBHQ treatment, was not found to affect
      either induction of the antioxidant response nor stellate cell
      transdifferentiation. These data implicate involvement of PI3K pathways in tBHQ
      mediated stellate cell activation and demonstrate a requirement for PI3K in the
      antioxidant response of hepatic stellate cells.

PMID- 16455044
TI  - Homocysteine transport by human aortic endothelial cells: identification and
      properties of import systems.
AB  - Hyperhomocysteinemia is an independent risk factor for cardiovascular disease.
      Transport of L-homocysteine into and out of the human vascular endothelium is
      poorly understood. We hypothesized that cultured human aortic endothelial cells
      (HAEC) would import L-homocysteine on one or more of the L-cysteine transport
      systems. Inhibitors of the transporters were used to characterize the uptake of
      [35S]L-homocysteine, [35S]L-homocystine, and [35S]L-cysteine. We found that L
      homocysteine uptake is mediated by the sodium-dependent cysteine transport
      systems X(AG), ASC, and A, and the sodium-independent transport system L. Thus,
      HAEC utilize multiple cysteine transporters (X(AG) > or = L > ASC > A) to import
      L-homocysteine. Kinetic analysis supported the uptake results. Michaelis-Menten
      constants (Km) for the four systems yielded values of 19.0, 27.1, 112, and 1000
      microM for systems L, X(AG), ASC, and A, respectively. The binding and uptake of
      [35S]L-homocystine, the disulfide homodimer of L-homocysteine, was mediated by
      systems X(AG), L, and ASC but not by system A. In contrast to [35S]L
      homocysteine, system x(c) was active for [35S]L-homocystine uptake. A similar
      pattern was observed for [35S]L-cysteine. Thus, L-homocysteine and L-homocystine
      found in hyperhomocysteinemic subjects can gain entry into the vascular
      endothelium by way of multiple L-cysteine transporters.

PMID- 16455046
TI  - Alterations in intracellular calcium homeostasis and platelet aggregation induced
      by ethanol.
AB  - The in vitro effects of ethanol on intracellular Ca(2+) homeostasis and tyrosine
      phosphorylation have been investigated in human platelets in order to clarify the
      cellular mechanisms underlying its described anti-aggregant effects. Ethanol (1
      50 mM) reduced, in a dose-dependent manner, the rate and amplitude of aggregation
      and attenuated the phosphotyrosine content both induced by 0.1U/ml of the
      physiological ligand, thrombin. Thrombin-induced Ca(2+) entry to the cytosol was
      significantly reduced, and capacitative Ca(2+) entry (CCE) significantly altered,
      by 50 mM ethanol, so that ethanol reduces CCE mediated by depletion of the 2,5-di
      (tert-butyl)-1,4-hydroquinone (TBHQ)-sensitive store but enhances CCE induced by
      the TBHQ-insensitive pool. In conclusion, we provide considerable evidence that
      ethanol reduces thrombin-induced aggregation, which is likely a result of a
      significant inhibition of Ca(2+) entry, as well as a reduction in the activity of
      protein tyrosine kinases.

PMID- 16455045
TI  - Insights into the molecular mechanism of action of Celastraceae sesquiterpenes as
      specific, non-transported inhibitors of human P-glycoprotein.
AB  - Dihydro-beta-agarofuran sesquiterpenes from Celastraceae have been recently shown
      to bind to human P-glycoprotein (Pgp), functioning as specific, mixed-type
      inhibitors of its drug transport activity, as well as multidrug resistance (MDR)
      modulators in vitro. However, nothing is known about whether such compounds are
      themselves transported by Pgp, or whether they affect Pgp expression as well as
      its activity, or about the location of their binding site within the protein. We
      performed transport experiments with a newly synthesized fluorescent
      sesquiterpene derivative, which retains the anti-Pgp activity of its natural
      precursor. This probe was poorly transported by Pgp, MRP1, MRP2 and BCRP
      transporters, compared with classical MDR substrates. Moreover, Pgp did not
      confer cross-resistance to the most potent dihydro-beta-agarofurans, which did
      not affect Pgp expression levels in several MDR cell lines. Finally, we observed
      competitive and non-competitive interactions between one of such dihydro-beta
      agarofurans (Mama12) and classical Pgp modulators such as cyclosporin A,
      verapamil, progesterone, vinblastine and GF120918. These findings suggest that
      multidrug ABC transporters do not confer resistance to dihydro-beta-agarofurans
      and could not affect their absorption and biodistribution in the body. Moreover,
      we mapped their binding site(s) within Pgp, which may prove useful for the
      rational design of improved modulators based on the structure of dihydro-beta
      agarofurans.

PMID- 16455047
TI  - Analysis of major intracellular proteins of Aspergillus fumigatus by MALDI mass
      spectrometry: identification and characterisation of an elongation factor 1B
      protein with glutathione transferase activity.
AB  - Aspergillus fumigatus is a recognised human pathogen, especially in
      immunocompromised individuals. The availability of the annotated A. fumigatus
      genome sequence will significantly accelerate our understanding of this organism.
      However, limited information is available with respect to the A. fumigatus
      proteome. Here, both a direct proteomic approach (2D-PAGE and MALDI-MS) and a sub
      proteomic strategy involving initial glutathione affinity chromatography have
      been deployed to identify 54 proteins from A. fumigatus primarily involved in
      energy metabolism and protein biosynthesis. Furthermore, two novel eukaryotic
      elongation factor proteins (eEF1Bgamma), termed ElfA and B have been identified
      and phylogenetically confirmed to belong to the eEF1Bgamma class of GST-like
      proteins. One of these proteins (ElfA) has been purified to homogeneity,
      identified as a monomeric enzyme (molecular mass=20 kDa; pI=5.9 and 6.5), and
      found to exhibit glutathione transferase activity specific activities (mean+/
      standard deviation, n=3) of 3.13+/-0.27 and 3.43+/-1.0 micromol/min/mg, using
      CDNB and ethacrynic acid, respectively. Overall, these data highlight the
      importance of new approaches to dissect the proteome of, and elucidate novel
      functions within, A. fumigatus.

PMID- 16455048
TI  - Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/-
      mice.
AB  - Since parathyroid hormone (PTH) increased FGF2 mRNA and protein expression in
      osteoblasts, and serum FGF-2 was increased in osteoporotic patients treated with
      PTH, we assessed whether the anabolic effect of PTH was impaired in Fgf2-/- mice.
      Eight-week-old Fgf2+/+ and Fgf2-/- male mice were treated with rhPTH 1-34
      (80mug/kg) for 4 weeks. Micro-CT and histomorphometry demonstrated that PTH
      significantly increased parameters of bone formation in femurs from Fgf2+/+ mice
      but the changes were smaller and not significant in Fgf2-/- mice. IGF-1 was
      significantly reduced in serum from PTH-treated Fgf2-/- mice. DEXA analysis of
      femurs from Fgf2+/+, Fgf2+/-, and Fgf2-/- mice treated with rhPTH (160mug/kg) for
      10 days showed that PTH significantly increased femoral BMD in Fgf2+/+ by 18%; by
      only 3% in Fgf2+/- mice and reduced by 3% in Fgf2-/- mice. We conclude that
      endogenous Fgf2 is important for maximum bone anabolic effect of PTH in mice.

PMID- 16455050
TI  - The N-terminal domain of tumor suppressor p53 is involved in the molecular
      interaction with the anti-apoptotic protein Bcl-Xl.
AB  - Emerging evidences suggest that transcription-independent mechanism of p53
      appears to make an important contribution to the overall p53-dependent apoptosis.
      Recently, it has been postulated that the DNA-binding domain of p53 can interact
      with Bcl-Xl, and subsequently the proposed molecular interaction has been shown
      by NMR studies. Interestingly, Chipuk et al. [Cancer Cell 4 (2003) 371] reported
      that the N-terminal domain of p53 (p53NTD) alone is necessary and sufficient to
      induce transcription-independent apoptosis. To further define and understand the
      nature of the molecular recognition between p53 and Bcl-Xl, our current study
      focuses on p53NTD. We first demonstrated the molecular interaction between p53NTD
      and Bcl-Xl by co-expressing and purifying the complex. Second, to define the
      binding interface of the molecular interaction, which is not previously
      characterized, in the current we employed a NMR-based binding study, showing that
      the binding site on Bcl-Xl is located in the region including alpha4, the N- and
      C-termini of alpha3, the N-terminus of alpha5, and the central part of alpha2. To
      further probe this observation, we then performed fluorescence resonance energy
      transfer (FRET) assay in cells. The FRET efficiency detected between the donor
      and acceptor molecules appears to suggest the presence of molecular interaction
      of p53NTD with Bcl-Xl in cells. Taken together, our data suggest that p53NTD
      interacts with Bcl-Xl but the characteristic of the molecular interaction appears
      to be different from that of the DNA-binding domain of p53.

PMID- 16455049
TI  - Direct inhibition of a PKA inhibitor, H-89 on KV channels in rabbit coronary
      arterial smooth muscle cells.
AB  - We examined the effects of the protein kinase A (PKA) inhibitor H-89 on voltage
      dependent K(+) (K(V)) currents in freshly isolated rabbit coronary arterial
      smooth muscle cells, using a whole-cell patch clamp technique. H-89 inhibited the
      K(V) current in a concentration-dependent manner, with a K(d) value of 1.02
      microM. However, the PKA inhibitors KT 5720 and Rp-8-CPT-cAMPS did not
      significantly alter the K(V) current or the inhibitory effects of H-89 on the
      K(V) current. Moreover, H-85, a structurally similar but inactive analog of H-89,
      showed similar inhibitory effects on the K(V) channel. H-89 had no effect on the
      voltage-dependency of activation or inactivation, or on recovery kinetics. These
      results suggest that in rabbit coronary arterial smooth muscle cells, H-89
      inhibits the K(V) current directly by blocking the pore cavity, an effect
      independent of PKA inhibition.

PMID- 16455051
TI  - Metalloantibiotic Mn(II)-bacitracin complex mimicking manganese superoxide
      dismutase.
AB  - Superoxide dismutase (SOD) activities of various metallobacitracin complexes were
      evaluated using the riboflavin-methionine-nitro blue tetrazolium assay. The
      radical scavenging activity of various metallobacitracin complexes was shown to
      be higher than those of the negative controls, e.g., free transition metal ions
      and metal-free bacitracin. The SOD activity of the complex was found to be in the
      order of Mn(II)>Cu(II)>Co(II)>Ni(II). Furthermore, the effect of bacitracin and
      their complexation to metals on various microorganisms was assessed by antibiotic
      susceptibility testing. Moreover, molecular modeling and quantum chemical
      calculation of the metallobacitracin complex was performed to evaluate the
      correlation of electrostatic charge of transition metal ions on the SOD activity.

PMID- 16455052
TI  - Vascular endothelial growth factor restores erectile function through modulation
      of the insulin-like growth factor system and sex hormone receptors in diabetic
      rat.
AB  - Previous studies have shown that intracavernous injection of vascular endothelial
      growth factor (VEGF) restored erectile function in diabetic rats. However, the
      mechanism of VEGF in diabetes-related erectile dysfunction (ED) has not been
      fully investigated. We hypothesize that intracavernous injection of VEGF may
      reverse diabetes-related ED through modulation of the insulin-like growth factor
      system and sex hormone receptors. To test this hypothesis the erectile function
      of treated and control rats was analyzed by measurement of intracavernous
      pressure (ICP) following electrostimulation of the cavernous nerves. Mean ICP was
      significantly lower in non-treated diabetic rats compared to controls. After VEGF
      injection, ICP was significantly higher than in non-treated diabetic rats. IGFBP
      3 mRNA and protein expression was significantly higher in non-treated diabetic
      rat crura than controls, while VEGF-treated animals had control levels. ER-beta
      and PR mRNA and protein expression was significantly lower in non-treated
      diabetic rat crura. After VEGF injection, ER-beta and PR mRNA and protein
      expression was similar to control levels. Expression of AR and ER-alpha was the
      same in all groups. These findings suggest that orthotopic injection of VEGF may
      improve the functional recovery of diabetes-related ED through modulation of the
      insulin-like growth factor system and sex hormone receptors. To our knowledge,
      this is the first study demonstrating that VEGF treatment restores erectile
      function through restoration of the insulin-like growth factor system and sex
      hormone receptor genes at the mRNA and protein levels in diabetic rat crura.
      These results may be important in understanding the pathogenesis of diabetes
      related ED and also in providing better strategies for management of this
      disease.

PMID- 16455053
TI  - NMR studies of Escherichia coli acyl carrier protein: dynamic and structural
      differences of the apo- and holo-forms.
AB  - Two indicators of conformational variability of Escherichia coli acyl carrier
      protein (ACP) have been investigated, namely backbone dynamics and chemical shift
      variations of ACP. Hydrophobic interactions between the 4'-PP prosthetic group
      and the hydrophobic pocket enclosed by the amphipathic helices resulted in
      chemical shift perturbations in the residues near the prosthetic group binding
      sites and contact sites in the hydrophobic pockets upon conversion from apo- to
      holo-forms. At pH 7.9, destabilization of ACP due to negative charge repulsions
      and the deprotonated state of His 75 resulted in observed chemical shift changes
      in the C-terminal region. Model-free analysis showed that the alpha(1)alpha(2)
      loop region near the prosthetic group binding site in ACP shows the greatest
      flexibility (lowest S(2) values) and this result may suggest these flexibilities
      are required for structural rearrangements when the acyl chain binds to the
      prosthetic group of ACP. Flexibility of ACP shown in this study is essential for
      its ability to interact with functionally different enzyme partners specifically
      and weakly in the rapid delivery of acyl chain from one partner to another.

PMID- 16455054
TI  - Subcellular localization and regulation of type-1C and type-5 phosphodiesterases.
AB  - We investigated the subcellular localization of PDE5 in in vitro human myometrial
      cells. We demonstrated for the first time that PDE5 is localized in discrete
      cytoplasmic foci and vesicular compartments corresponding to centrosomes. We also
      found that PDE5 intracellular localization is not cell- or species-specific, as
      it is conserved in different animal and human cells. PDE5 protein levels are
      strongly regulated by the mitotic activity of the smooth muscle cells (SMCs), as
      they were increased in quiescent, contractile myometrial cultures, and conditions
      in which proliferation was inhibited. In contrast, PDE1C levels decreased in all
      conditions that inhibited proliferation. This mirrored the enzymatic activity of
      both PDE5 and PDE1C. Increasing cGMP intracellular levels by dbcGMP or sildenafil
      treatments did not block proliferation, while dbcAMP inhibited myometrial cell
      proliferation. Together, these results suggest that PDE5 regulation of cGMP
      intracellular levels is not involved in the control of SMC cycle progression, but
      may represent one of the markers of the contractile phenotype.

PMID- 16455055
TI  - Evidence for the interaction of the regulatory protein Ki-1/57 with p53 and its
      interacting proteins.
AB  - Ki-1/57 is a cytoplasmic and nuclear phospho-protein of 57 kDa and interacts with
      the adaptor protein RACK1, the transcription factor MEF2C, and the chromatin
      remodeling factor CHD3, suggesting that it might be involved in the regulation of
      transcription. Here, we describe yeast two-hybrid studies that identified a total
      of 11 proteins interacting with Ki-1/57, all of which interact or are
      functionally associated with p53 or other members of the p53 family of proteins.
      We further found that Ki-1/57 is able to interact with p53 itself in the yeast
      two-hybrid system when the interaction was tested directly. This interaction
      could be confirmed by pull down assays with purified proteins in vitro and by
      reciprocal co-immunoprecipitation assays from the human Hodgkin analogous
      lymphoma cell line L540. Furthermore, we found that the phosphorylation of p53 by
      PKC abolishes its interaction with Ki-1/57 in vitro.

PMID- 16455056
TI  - Array CGH analysis reveals chromosomal aberrations in mouse lung adenocarcinomas
      induced by the human lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone.
AB  - Exposure to genotoxic carcinogens in tobacco smoke is a major cause of lung
      cancer. However, the effect this has on DNA copy number and genomic stability
      during lung carcinogenesis is unclear. Here we used bacterial artificial
      chromosome array-based comparative genomic hybridization to examine the effect of
      NNK, a potent human lung carcinogen present in tobacco smoke, on the major
      genomic changes occurring during mouse lung adenocarcinogenesis. Observed were
      significantly more gross chromosomal changes in NNK-induced tumors compared with
      the spontaneous tumors. An average of 5.6 chromosomes were affected by large
      scale changes in DNA copy number per NNK-induced tumor compared with only 2.0 in
      spontaneous lung tumors (p = 0.017). Further analysis showed that gains on
      chromosomes 6 and 8, and losses on chromosomes 11 and 14 were more common in NNK
      induced tumors (p <or= 0.002). The changes on chromosomes 8, 11, and 14 were
      positively (p <or= 0.001) associated with the degree of chromosome instability
      (CIN). This association was less significant for gains on chromosomes 6 and 12 (p
      = 0.035). In contrast, loss of distal chromosome 4 was very frequent (71%) in
      both NNK-induced and spontaneous tumors, and showed no association with CIN
      phenotype. Each of these chromosomes contains sites of orthology with those
      altered in human lung adenocarcinomas, suggesting similar roles in human lung
      cancer. We next investigated the mechanism of NNK-induced CIN and found that a
      genotoxic metabolite of this carcinogen causes numerous karyotypic changes in
      lung epithelial cells. With similar changes evident in NNK-induced tumors, this
      suggests that the persistence of such damage in exposed lung epithelia may
      initiate CIN during lung carcinogenesis. These results show for the first time
      that NNK potently induces gross chromosomal alterations in lung
      adenocarcinogenesis and modulates the evolutionary pathway of these tumors
      through the recruitment of genes with altered DNA copy number.

PMID- 16455057
TI  - Functional heterogeneity of side population cells in skeletal muscle.
AB  - Skeletal muscle regeneration has been exclusively attributed to myogenic
      precursors, satellite cells. A stem cell-rich fraction referred to as side
      population (SP) cells also resides in skeletal muscle, but its roles in muscle
      regeneration remain unclear. We found that muscle SP cells could be subdivided
      into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in
      normal non-regenerating muscle expressed CD31 and had endothelial
      characteristics. However, CD31(-)CD45(-) SP cells, which are a minor
      subpopulation in normal muscle, actively proliferated upon muscle injury and
      expressed not only several regulatory genes for muscle regeneration but also some
      mesenchymal lineage markers. CD31(-)CD45(-) SP cells showed the greatest myogenic
      potential among three SP sub-fractions, but indeed revealed mesenchymal
      potentials in vitro. These SP cells preferentially differentiated into myofibers
      after intramuscular transplantation in vivo. Our results revealed the
      heterogeneity of muscle SP cells and suggest that CD31(-)CD45(-) SP cells
      participate in muscle regeneration.

PMID- 16455058
TI  - Functional expression of metabotropic GABAB receptors in primary cultures of
      astrocytes from rat cerebral cortex.
AB  - GABA(B) receptor subunits are widely expressed on neurons throughout the central
      nervous system (CNS), at both pre- and postsynaptic sites, where they mediate the
      late and slow component of the inhibitory response to the major inhibitory
      neurotransmitter GABA. Recently, GABA(B) receptors have been reported to be
      expressed in astrocytes and microglia in the rat CNS by immunocytochemistry.
      However, there are few reports available for the functional characterization of
      GABA(B) receptors on astrocytes. In the present study, we therefore investigated
      the functional expression and characteristics of GABA(B) receptors in primary
      cultures of astrocytes from rat cerebral cortex. In the presence of 10 microM
      GTP, forskolin concentration-dependently increased adenylylcyclase (AC) activity
      in membranes prepared from rat astrocytes. The selective GABA(B) agonist (R)
      baclofen concentration-dependently reduced forskolin-stimulated AC activity in
      the presence of 10 microM GTP. This effect was reversed by the selective GABA(B)
      antagonists, CGP-55845 and CGP-54626, and was completely abolished by treatment
      of astrocytic membranes with pertussis toxin. In addition, RT-PCR, Western
      blotting, and immunocytochemistry clearly showed that metabotropic GABA(B)
      receptor isoforms (GABA(B)R1 and GABA(B)R2) are expressed in rat cerebrocortical
      astrocytes. Taken collectively, these results demonstrate that functionally
      active metabotropic GABA(B) receptors are expressed in rat cerebrocortical
      astrocytes.

PMID- 16455059
TI  - The effect of methadone and buprenorphine on human placental aromatase.
AB  - Methadone and buprenorphine (BUP) are used for treatment of the pregnant opiate
      addict. CYP19/aromatase is the major placental enzyme responsible for the
      metabolism of methadone to 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine
      (EDDP) and BUP to norbuprenorphine (norBUP). The aim of this investigation was to
      determine the effects of methadone and BUP on the activity of placental
      microsomal aromatase in the conversion of its endogenous substrates testosterone
      to 17beta-estradiol (E(2)) and 16alpha-hydroxytestosterone (16-OHT) to estriol
      (E(3)). The conversion of testosterone and 16-OHT by human placental microsomes
      exhibited saturation kinetics, and the apparent K(m) values were 0.2 +/- 1 and 6
      +/- 3 microM, respectively. V(max) values for E(2) and E(3) formation were 70 +/-
      16 and 28 +/- 10 pmol/mg proteinmin, respectively. Also, data obtained revealed
      that methadone and BUP are competitive inhibitors of testosterone conversion to
      E(2) and 16-OHT to E(3). The K(i) for methadone inhibition of E(2) and E(3)
      formation were 393 +/-144 and 53 +/- 28 microM, respectively, and for BUP the
      K(i) was 36 +/- 9 and 6 +/- 1 microM. The higher potency of the two opiates and
      their metabolites in inhibiting E(3) formation is in agreement with the lower
      affinity of 16-OHT than testosterone to aromatase. Moreover, the metabolites EDDP
      and norBUP were weaker inhibitors of aromatase than their parent compounds. The
      determined inhibition constants of methadone and BUP for E(3) formation by a cDNA
      expressed CYP19 preparation were similar to those for placental microsomes.
      Therefore, data reported here suggest that methadone, BUP, and their metabolites
      are inhibitors of androgen aromatization in the placental biosynthesis of
      estrogens.

PMID- 16455060
TI  - In vitro-in vivo correlation for drugs and other compounds eliminated by
      glucuronidation in humans: pitfalls and promises.
AB  - Enzymes of the UDP-glucuronosyltransferase (UGT) superfamily are responsible for
      the metabolism of many drugs, environmental chemicals and endogenous compounds.
      Identification of the UGT(s) involved in the metabolism of a given compound
      ('reaction phenotyping') currently relies on multiple confirmatory approaches,
      which may be confounded by the dependence of UGT activity on enzyme source,
      incubation conditions, and the occurrence of atypical glucuronidation kinetics.
      However, the increasing availability of substrate and inhibitor 'probes' for the
      individual UGTs provides the prospect for reliable phenotyping of glucuronidation
      reactions using human liver microsomes or hepatocytes, thereby providing data
      directly relevant to drug metabolism in humans. While the feasibility of
      computational prediction of UGT substrate selectivity has been demonstrated, the
      development of easily interpretable and generalisable models requires further
      improvement in the datasets available for analysis. Quantitative prediction of
      the hepatic clearance of glucuronidated drugs and the magnitude of inhibitory
      interactions based on in vitro kinetic data is more problematic. Intrinsic
      clearance (CL(int)) values generated using human liver microsomes under-predict
      in vivo hepatic clearance, typically by an order of magnitude. In vivo clearances
      of glucuronidated drugs are also generally under-predicted by CL(int) values from
      human hepatocytes, but to a lesser extent than observed with the microsomal
      model. While it is anticipated that systematic analysis of the potential causes
      of under-prediction may provide more reliable in vitro-in vivo scaling
      strategies, mechanistic interpretation of in vitro-in vivo correlation more
      broadly awaits further advances in our understanding of the structural and
      cellular determinants of UGT activity.

PMID- 16455062
TI  - Synaptic transmission changes in the pyramidal cells of the hippocampus in
      streptozotocin-induced diabetes mellitus in rats.
AB  - The central nervous system complications of diabetes mellitus (DM) include
      defects in hippocampal synaptic plasticity induction and difficulties in learning
      and memory. DM was induced by streptozotocin (STZ) injection in rats. After 12
      weeks of DM duration, the rats were decapitated, and hippocampal slices were
      prepared for in vitro study. Field excitatory postsynaptic potentials (fEPSP)
      were recorded after repeated stimulations with 50 impulses given either in 10 or
      20 Hz. The responses were significantly smaller in the diabetic animals than in
      the age-matched control rats. The summation of alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) responses was tested in both groups by
      stimulating the synapses with five consecutive stimuli given in 50-Hz frequency.
      Intracellular recording from the pyramidal hippocampal cells of the AMPA
      summation responses from diabetic and aged-matched control animals revealed a
      significant lower summation in the diabetic animals compared to the control. It
      is concluded that responses evoked by high-frequency stimulation (HFS) were
      significantly higher in the control animals. The defects in diabetic slices could
      be related to pre- as well as postsynaptic changes, and these defects play an
      important role in the synaptic plasticity changes seen in STZ-induced diabetic
      animals.

PMID- 16455061
TI  - Activation of 5-HT1A receptors in rostral medullary raphe inhibits cutaneous
      vasoconstriction elicited by cold exposure in rabbits.
AB  - In both conscious and anesthetized rabbits, we determined whether microinjection
      of a 5-hydroxytryptamine (5-HT) 1A receptor agonist 8-hydroxy-2-(di-n
      propylaminio) tetralin (8-OH-DPAT) into the medullary raphe/parapyramidal region
      inhibits thermoregulatory vasoconstriction and whether microinjection of a 5-HT1A
      receptor antagonist (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2
      pyridinyl) cyclohexanecarboxamide trihydrochloride) (WAY-100635) into the raphe
      reverses the cutaneous vasomotor changes induced by intravenous administration of
      8-OH-DPAT. In conscious rabbits with measuring ear pinna blood flow, after
      microinjection of 8-OH-DPAT (3-5 nmol in 300-500 nl) into the raphe, transferring
      the animal from a warm cage (25-28 degrees C) to a cold cage (5-10 degrees C) did
      not reduce the ear pinna flow (from 57 +/- 7 cm/s to 59 +/- 3 cm/s, P > 0.05, n =
      5), unlike Ringer-treated animals. Microinjection of WAY-100635 (5 nmol in 500
      nl) into the raphe reversed ear pinna flow changes induced by intravenous
      administration of 8-OH-DPAT (0.1 mg/kg, i.v.). In anesthetized rabbits with
      measuring postganglionic ear pinna sympathetic nerve activity, microinjection of
      8-OH-DPAT (1-2 nmol in 100-200 nl) into the raphe reduced resting ear pinna
      sympathetic nerve activity to 14 +/- 4% of pre-injection level (P < 0.01, n = 12)
      and attenuated increases in ear pinna sympathetic nerve activity normally
      elicited by cooling the animal's trunk. WAY-100635 (2 nmol into 200 nl) into the
      raphe reversed inhibition of ear pinna sympathetic nerve activity elicited by 8
      OH-DPAT (0.1 mg/kg, i.v.). The activation of 5-HT1A receptors expressed on the
      medullary raphe neurons results in reversal of cold-elicited cutaneous
      vasoconstriction possibly through inhibition of sympathetic premotor neurons that
      innervate sympathetic preganglionic neurons controlling cutaneous vasomotion.

PMID- 16455063
TI  - Visually induced feelings of touch.
AB  - Recent studies have reported that vision can enhance tactile perception, even in
      patients with somatosensory deficits. However, it is unclear in these previous
      studies whether visual input truly enhances detection of tactile stimuli or
      induces a higher propensity for reporting touch by changing response criteria. In
      this study, we demonstrate in neurologically normal subjects that in addition to
      small increases in tactile sensitivity when a non-informative, suprathreshold
      visual stimulus is presented, there are highly consistent changes in response
      criteria for reporting touch with vision, even when no tactile stimulus is
      delivered. These results suggest that some of the previously reported
      enhancements of touch from vision may rather be a consequence of strategic
      sensory encoding processes that rely upon the typical correlations between
      multisensory events.

PMID- 16455064
TI  - Postnatal administration of D1 dopamine agonist reverses neonatal dopaminergic
      lesion-induced changes in striatal enkephalin and substance P systems.
AB  - The present study examined the effects of postnatal dopamine (DA) receptor
      stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP)
      systems of basal ganglia of rats, lesioned as neonates with 6-hydroxydopamine (6
      OHDA, intracisternally) on the third postnatal day. D1 agonist, SKF-38393 or D2
      agonist, LY-171555 (also known as quinpirole) was administered s.c. twice daily
      for 14 days, beginning 24 h after 6-OHDA administration. The animals were
      sacrificed at 60 days of age, and the concentrations of striatal DA, SP, and ME
      were determined by HPLC or radioimmunoassay. As expected, 6-OHDA induced a severe
      loss of DA, an increase in ME, and a decrease in SP. SKF-38393, but not,
      quinpirole significantly reversed the lesion-induced changes in ME and SP levels.
      The results indicate an important role for D1 receptors in the postnatal
      development of ME and SP systems in the striatum. These studies are relevant to
      our further understanding of potential early interventions in the progression and
      expression of DA deficiency states such as Parkinsonism and Lesch-Nyhan disease.

PMID- 16455065
TI  - Induction of neuronal differentiation of adult human olfactory neuroepithelial
      derived progenitors.
AB  - Neurosphere forming cells (NSFCs) have been established from cultures of adult
      olfactory neuroepithelium obtained from patients and cadavers as described
      previously. They remained undifferentiated in serum or defined media with or
      without neurotrophic factors. Many factors affect the differentiation of stem
      cells along a neuronal pathway. Retinoic acid (RA), forskolin (FN), and sonic
      hedgehog (Shh) have been reported to act as growth promoters during neurogenesis
      of embryonic CNS in vivo. The effect of RA, FN, and Shh on NSFCs' neuronal
      lineage restriction has not been described. The application of RA, FN, and Shh to
      NSFCs induced the expression of motoneuronal transcription factors, tyrosine
      hydroxylase, an indicator of dopamine production, and neurite formation. These
      studies further heighten the potential for using olfactory neuroepithelial
      progenitors for future autologous cell replacement strategies in
      neurodegenerative conditions and trauma as well as for use in diagnostic
      evaluation.

PMID- 16455066
TI  - Amadori-modified glycated albumin predominantly induces E-selectin expression on
      human umbilical vein endothelial cells through NADPH oxidase activation.
AB  - BACKGROUND: Protein glycation is closely linked to endothelial-cell dysfunction
      and vascular complications in diabetes. Glycated albumin is reported to induce
      cellular signaling similar to advanced glycation endoproducts (AGEs), however,
      cellular signaling remains obscure. METHOD: We stimulated human umbilical vein
      endothelial cells (HUVECs) by glycated human serum albumin (Glc-HSA), determined
      E-selectin expression by real-time PCR and immunometric methods, and estimated
      cellular signaling by using various signaling molecule inhibitors and confocal
      microscopy. RESULTS: Glc-HSA-induced E-selectin expression was 10 or 20 times
      more than that induced with 3 kinds of AGEs-HSAs, which was not suppressed by
      anti-receptor for AGEs (RAGE) antibody. Glc-HSA-induced E-selectin expression was
      completely suppressed by the NADPH oxidase inhibitor diphenylene iodonium
      chloride and the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine.
      Confocal microscopic analysis also revealed intracellular accumulation of ROS.
      Glc-HSA-induced E-selectin expression was suppressed by the phosphatidylinositol
      3 kinase (PI3K) inhibitors wortmannin and LY294002, the protein kinase B (PKB)
      inhibitor ML-9, the IkappaB kinase (IKK) inhibitor BAY117082, and the Jun N
      terminal kinase (JNK) inhibitor SP600125, On the other hand, the protein kinase C
      inhibitors calphostin C and H-7 did not suppress Glc-HSA-induced E-selectin
      expression. CONCLUSION: Glc-HSA induces activation of NADPH oxidase, PKB-IKK and
      JNK, then E-selectin gene transcription is upregulated by nuclear-translocated NF
      kappaB and AP-1.

PMID- 16455068
TI  - ECG signal compression by multi-iteration EZW coding for different wavelets and
      thresholds.
AB  - The modified embedded zero-tree wavelet (MEZW) compression algorithm for the one
      dimensional signal was originally derived for image compression based on
      Shapiro's EZW algorithm. It is revealed that the proposed codec is significantly
      more efficient in compression and in computation than previously proposed ECG
      compression schemes. The coder also attains exact bit rate control and generates
      a bit stream progressive in quality or rate. The EZW and MEZW algorithms apply
      the chosen threshold values or the expressions in order to specify that the
      significant transformed coefficients are greatly significant. Thus, two different
      threshold definitions, namely percentage and dyadic thresholds, are used, and
      they are applied for different wavelet types in biorthogonal and orthogonal
      classes. In detail, the MEZW and EZW algorithms results are quantitatively
      compared in terms of the compression ratio (CR) and percentage root mean square
      difference (PRD). Experiments are carried out on the selected records from the
      MIT-BIH arrhythmia database and an original ECG signal. It is observed that the
      MEZW algorithm shows a clear advantage in the CR achieved for a given PRD over
      the traditional EZW, and it gives better results for the biorthogonal wavelets
      than the orthogonal wavelets.

PMID- 16455067
TI  - The E23K polymorphism in Kir6.2 gene and coronary heart disease.
AB  - BACKGROUND: The G to A mutation in the Kir 6.2, the ATP-sensitive potassium
      channel subunit, resulted a glutamate (E) to lysine (K) substitution at codon 23,
      and the A allele was shown to have a relationship with high risk to type 2
      diabetes in previous study. Their role in coronary heart disease (CHD) has not
      been evaluated. We hypothesized that the polymorphism would be associated with
      increased susceptibility to CHD. METHODS: The E23K gene polymorphism of Kir6.2
      gene was analyzed by PCR-restriction site polymorphism (PCR-RSP) methods in 101
      controls and 119 CHD patients. Serum lipids and C reactive protein concentrations
      were measured in all subjects. RESULTS: Among the CHD patients, the frequency of
      the G allele was higher (63.4% vs. 56.9%, P>0.05) and the frequency of the A
      allele was lower (36.6% vs. 43.1%, P>0.05) than among controls. No significant
      differences were found in allele frequencies between CHD and controls (P>0.05),
      but there were significant differences in GG and combined (GA+AA) genotypes
      frequencies (42.0% vs. 28.7%, and 58.0% vs. 71.3%, P<0.050). CONCLUSIONS: The
      E23K gene polymorphism in Kir6.2 gene appeared to be related to high
      susceptibility to CHD.

PMID- 16455069
TI  - Characterisation of cryoinjury in Euglena gracilis using flow-cytometry and
      cryomicroscopy.
AB  - Flow-cytometry and cryomicroscopy elucidated that the unicellular algal protist
      Euglena gracilis was undamaged by cryoprotectant added at 0 degree C, and super
      cooling in the absence of ice. Cryoinjuries were however induced by: osmotic
      shock resulting from excessive cryodehydration, intracellular ice, and fracturing
      of the frozen medium on thawing. Suboptimal cooling at -0.3 degrees C min(-1) to 
      60 degrees C and osmotic shock invariably resulted in damage to the organism's
      pellicle and osmoregulatory system causing, a significant (P > 0.005) increase in
      cell size. Cell damage was not repairable and led to death. The responses of E.
      gracilis to cryopreservation as visualised by flow-cytometry and cryomicroscopy
      assisted the development of an improved storage protocol. This comprised:
      cryoprotection with methanol [10%(v/v)] at 0 degree C, cooling at 0.5 degrees C
      min(-1) to -60 degrees C, isothermal hold for 30 min, and direct immersion in
      liquid nitrogen. Highest post-thaw viability (>60%) was obtained using two-step
      thawing, which involved initial slow warming to -130 degrees C followed by
      relatively rapid warming (approximately 90 degrees C min(-1)) to ambient
      temperature (ca. 25 degrees C).

PMID- 16455070
TI  - Effects of a manganese (III) porphyrin catalytic antioxidant in a mouse closed
      head injury model.
AB  - Closed head injury induces cerebral oxidative stress. The efficacy of a Mn (III)
      porphyrin catalytic antioxidant was assessed in a mouse closed head injury model.
      Mice were subjected to closed head injury and treated 15 min later with an i.v.
      bolus of vehicle or 3 mg/kg MnTE-2-PyP5+. Aconitase activity, Fluoro-Jade
      staining, glial fibrillary acidic protein immunoreactivity, and rotarod falling
      latencies were measured. Closed head injury altered all variables. MnTE-2-PyP5+
      had no effect on any variable with the exception of attenuation of aconitase
      inactivation at 2 h post-closed head injury. In a second experiment, mice
      received 3 mg/kg or 6 mg/kg MnTE-2-PyP5+ or vehicle i.v. 15 min post-closed head
      injury. Rotarod and Morris water maze latencies were measured. Closed head injury
      altered performance in both tests. No statistically significant effect of MnTE-2
      PyP5+ was observed. We conclude that single dose MnTE-2-PyP5+ does not alter
      outcome in this mouse closed head injury model.

PMID- 16455071
TI  - Free immunoglobulin light chains as target in the treatment of chronic
      inflammatory diseases.
AB  - Immunoglobulin free light chains were long considered irrelevant bystander
      products of immunoglobulin synthesis by B lymphocytes. To date, different studies
      suggest that free light chains may have important functional activities. For
      instance, it has been shown that immunoglobulin free light chains can elicit mast
      cell-driven hypersensitivity responses leading to asthma and contact sensitivity.
      Free light chains also show other biologic actions such as anti-angiogenic and
      proteolytic activities or can be used as specific targeting vehicles. Levels of
      free light chain levels in body fluids increase markedly in diseases such as
      multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. In
      this review, we will focus on the unexpected biological activities of
      immunoglobulin free light chains with special attention to its possible role in
      the induction of chronic inflammatory diseases.

PMID- 16455072
TI  - Genetic deletion of muscarinic M4 receptors is anxiolytic in the shock-probe
      burying model.
AB  - We used muscarinic M2 and M4 receptor knockout (KO) mice to further explore the
      role of the cholinergic system in anxiety. Using the shock-probe burying model we
      were able to both assess anxiety and cognition. In this paradigm, an anxiolytic
      response is reflected by decreased burying behavior. In addition, retention
      latency depicts long-term memory performance. Whereas muscarinic M2 receptor KO
      mice did not differ behaviorally from wild-type mice, muscarinic M4 receptor KO
      mice showed increased anxiolysis, but normal long-term memory compared to wild
      type mice. Therefore, muscarinic M4 receptors are of particular significance in
      anxiety modulation that seems dissociated from changes in long-term memory.

PMID- 16455073
TI  - Peptide and non-peptide bradykinin receptor antagonists: role in allergic airway
      disease.
AB  - Kinins are proinflammatory peptides that mediate a variety of pathophysiological
      responses. These actions occur through stimulation of two pharmacologically
      distinct receptor subtypes B1 and B2. In both human and animal airways, the
      majority of kinin-induced effects including bronchoconstriction, increases in
      vascular permeability and mucus secretion and cholinergic and sensory nerve
      stimulation appear to be bradykinin B2-receptor mediated. Peptidic and non
      peptidic receptor antagonists have been developed as potential therapeutic
      agents. These antagonists are effective in blocking kinin-induced effects in a
      variety of animal models and in some instances, have been used effectively in
      animal models of allergic airway disease to alleviate allergen-induced
      pathophysiological airway responses. This review summarizes relevant studies
      supporting the evidence that bradykinin B2 receptor antagonism and/or upstream
      inhibition of tissue kallikrein will be beneficial in the treatment of
      inflammatory airway diseases.

PMID- 16455074
TI  - Different activity regulation and subcellular localization of LIMK1 and LIMK2
      during cell cycle transition.
AB  - LIM kinases (LIMK1 and LIMK2) regulate actin cytoskeletal reorganization through
      phosphorylating and inactivating cofilin, an actin-depolymerizing factor of actin
      filaments. Here, we describe a detailed analysis of the cell-cycle-dependent
      activity of LIMK2, and a subcellular localization of LIMK1 and LIMK2. The
      activity of LIMK2, distinct from LIMK1, toward cofilin phosphorylation did not
      change in the normal cell division cycle. In contrast, LIMK2 was
      hyperphosphorylated and its activity was markedly increased when HeLa cells were
      synchronized at mitosis with nocodazole treatment. Immunofluorescence analysis
      showed that LIMK1 was localized at cell-cell adhesion sites in interphase and
      prophase, redistributed to the spindle poles during prometaphase to anaphase, and
      accumulated at the cleavage furrow in telophase. In contrast, LIMK2 was diffusely
      localized in the cytoplasm during interphase, redistributed to the mitotic
      spindle, and finally to the spindle midzone during anaphase to telophase. These
      findings suggest that LIMK2 is activated in response to microtubule disruption,
      and that LIMK1 and LIMK2 may play different roles in regulating for the mitotic
      spindle organization, chromosome segregation, and cytokinesis during the cell
      division cycle.

PMID- 16455075
TI  - Plastic downregulation of the transcriptional repressor BCL6 during maturation of
      human dendritic cells.
AB  - Dendritic cell (DC) maturation links peripheral events initiated by the encounter
      with pathogens to the activation and expansion of antigen-specific T lymphocytes
      in secondary lymphoid organs. Here, we describe an as yet unrecognized modulator
      of human DC maturation, the transcriptional repressor BCL6. We found that both
      myeloid and plasmacytoid DCs constitutively express BCL6, which is rapidly
      downregulated following maturation triggered by selected stimuli. Both in
      unstimulated and maturing DCs, control of BCL6 protein levels reflects the
      convergence of several mechanisms regulating BCL6 stability, mRNA transcription
      and nuclear export. By regulating the induction of several genes implicated in
      the immune response, including inflammatory cytokines, chemokines and survival
      genes, BCL6 may represent a pivotal modulator of the afferent branch of the
      immune response.

PMID- 16455076
TI  - Silencing of human alpha-synuclein in vitro and in rat brain using lentiviral
      mediated RNAi.
AB  - Human alpha-synuclein overexpression and its toxic accumulation in neurons or
      glia are known to play key roles in the pathogenesis of Parkinson's disease and
      other related neurodegenerative synucleinopathies. Several single point mutations
      in the alpha-synuclein gene, as well as gene duplication and triplication, have
      been linked to familial Parkinson's disease. Moreover, genetic variability of the
      alpha-synuclein gene promoter is associated with idiopathic Parkinson's disease.
      Silencing of the human alpha-synuclein gene by vector-based RNA interference
      (RNAi) is a promising therapeutic approach for synucleinopathies. Here, we report
      identification of a 21-nucleotide sequence in the coding region of human alpha
      synuclein that constitutes an effective target for robust silencing by RNAi and
      demonstrate allele-specific silencing of the A53T mutant of human alpha
      synuclein. Furthermore, we have developed a plasmid vector-based RNAi for
      silencing of human alpha-synuclein in vitro. Lastly, using a dual cassette
      lentivirus that co-expresses an alpha-synuclein-targeting small hairpin RNA
      (shRNA) and enhanced green fluorescent protein (EGFP) as a marker gene, we
      demonstrate effective silencing of endogenous human alpha-synuclein in vitro in
      the human dopaminergic cell line SH-SY5Y and also of experimentally expressed
      human alpha-synuclein in vivo in rat brain. Our results demonstrate potent
      silencing of human alpha-synuclein expression in vitro and in vivo by viral
      vector-based RNAi and provide the tools for developing effective gene silencing
      therapeutics for synucleinopathies, including Parkinson's disease.

PMID- 16455078
TI  - In vivo three-dimensional reconstruction of human median nerves by diffusion
      tensor imaging.
AB  - The in vivo assessment of axonal projections of the peripheral nervous system has
      been severely limited by the lack of noninvasive techniques. We examined whether
      MR diffusion tensor imaging with fiber tracking of the human median nerve is
      feasible. The median nerve was examined with a 3-T MRI scanner in wrists of three
      healthy volunteers and the wrist of a patient after median nerve repair. In vivo
      three-dimensional (3D) reconstruction of axonal projections of the median nerve
      could be achieved in healthy volunteers with intact median nerves and a patient
      with a transected median nerve using diffusion tensor imaging combined with fiber
      tracking. The median nerve could be visualized and correlated well to the
      expected location on T1-weighted images in the patient and all volunteers. The
      transected median nerve in the patient could be detected up to the site of repair
      one month postoperatively, whereas the nerve could not be detected more distally
      immediately after repair. Two months postoperatively, it could clearly be tracked
      more distally, indicating nerve regeneration. Diffusion tensor imaging can detect
      the median nerve in healthy individuals as well as up to the lesion site in a
      patient with a complete transection of the median nerve.

PMID- 16455077
TI  - Molecular mapping of striatal subdivisions in juvenile Macaca Mulata.
AB  - The striatum of the primate brain can be subdivided into three distinct
      anatomical subregions: caudate (CAU), putamen (PUT), and ventral striatum (VS).
      Although these subregions share several anatomical connections, cell
      morphological, and histochemical features, they differ considerably in their
      vulnerability to different neurological and psychiatric diseases, and these brain
      regions have significantly different functions in health and disease. In order to
      better understand the molecular underpinnings of the different disease and
      functional vulnerabilities, transcriptional profiles were generated from the CAU,
      PUT, and VS of five juvenile rhesus macaques (Macaca mulatta) using human cDNA
      neuromicroarrays containing triplicate spots of 1227 cDNAs. Differences in
      microarray gene expression were assessed using z score analysis and 1.5-fold
      change between paired subregions. Clustering of genes based on dissimilarity of
      expression patterns between regions revealed subregion specific expression
      profiles encoding G-protein-coupled receptor signaling transcripts, transcription
      factors, kinases and phosphatases, and cell signaling and signal transduction
      transcripts. Twelve transcripts were examined using quantitative real-time PCR
      (qPCR), and 81% demonstrated alterations similar to those seen with microarray
      analysis, some of which were statistically significant. Subregion specific
      transcription profiles support the anatomical differentiation and potential
      disease vulnerabilities of the respective subregions.

PMID- 16455079
TI  - MRI volumetric and intensity analysis of the cerebellum in Parkinson's disease
      patients infused with glial-derived neurotrophic factor (GDNF).
AB  - BACKGROUND: A recent human therapeutic trial using intraputaminal infusion of
      glial cell-derived neurotrophic factor (GDNF) in Parkinson's disease (PD) was
      abruptly terminated, partly due to safety concerns raised by the finding of
      cerebellar lesions in monkeys given high-dose GDNF. METHODS: Magnetic resonance
      images from nine PD patients participating in this trial were analyzed to
      determine whether subtle volumetric or intensity changes could be detected in the
      cerebellum or elsewhere following GDNF treatment for over 1 year. Subtraction
      images were compared to a reference standard deviation map constructed by using
      identically-processed paired scans from 25 normal adults. In a separate voxel
      based group morphometric (VBM) analysis of the same patient images, grey matter
      intensity was compared between pre and post-GDNF infusion scans using a repeated
      measures ANOVA with family-wise error threshold of P = 0.10. Two expert readers
      independently reviewed serial FLAIR images from all patients. RESULTS: (1) There
      were no significant cerebellar differences in any of the nine individual PD
      patients (difference image analysis), (2) there were no significant morphometric
      differences between pre- and post-GDNF scans (VBM), and (3) there were no signal
      abnormalities in the cerebellum detected on the FLAIR images in PD patients
      (clinical scan review). CONCLUSIONS: In concert with lack of evidence of
      cerebellar dysfunction on clinical examination, we find no imaging evidence of
      cerebellar injury in human subjects undergoing chronic intracerebral GDNF
      infusion.

PMID- 16455080
TI  - Allogeneic bone marrow stromal cells promote glial-axonal remodeling without
      immunologic sensitization after stroke in rats.
AB  - We evaluated the effects of allogeneic bone marrow stromal cell treatment of
      stroke on functional outcome, glial-axonal architecture, and immune reaction.
      Female Wistar rats were subjected to 2 h of middle cerebral artery occlusion.
      Rats were injected intravenously with PBS, male allogeneic ACI--or syngeneic
      Wistar--bone marrow stromal cells at 24 h after ischemia and sacrificed at 28
      days. Significant functional recovery was found in both cell-treated groups
      compared to stroke rats that did not receive BMSCs, but no difference was
      detected between allogeneic and syngeneic cell-treated rats. No evidence of T
      cell priming or humoral antibody production to marrow stromal cells was found in
      recipient rats after treatment with allogeneic cells. Similar numbers of Y
      chromosome+ cells were detected in the female rat brains in both groups.
      Significantly increased thickness of individual axons and myelin, and areas of
      the corpus callosum and the numbers of white matter bundles in the striatum were
      detected in the ischemic boundary zone of cell-treated rats compared to stroked
      rats. The areas of the contralateral corpus callosum significantly increased
      after cell treatment compared to normal rats. Processes of astrocytes remodeled
      from hypertrophic star-like to tadpole-like shape and oriented parallel to the
      ischemic regions after cell treatment. Axonal projections emanating from
      individual parenchymal neurons exhibited an overall orientation parallel to
      elongated radial processes of reactive astrocytes of the cell-treated rats.
      Allogeneic and syngeneic bone marrow stromal cell treatment after stroke in rats
      improved neurological recovery and enhanced reactive oligodendrocyte and
      astrocyte related axonal remodeling with no indication of immunologic
      sensitization in adult rat brain.

PMID- 16455082
TI  - Redox regulation of peroxiredoxin and proteinases by ascorbate and thiols during
      pea root nodule senescence.
AB  - Redox factors contributing to nodule senescence were studied in pea. The
      abundance of the nodule cytosolic peroxiredoxin but not the mitochondrial
      peroxiredoxin protein was modulated by ascorbate. In contrast to redox-active
      antioxidants such as ascorbate and cytosolic peroxiredoxin that decreased during
      nodule development, maximal extractable nodule proteinase activity increased
      progressively as the nodules aged. Cathepsin-like activities were constant
      throughout development but serine and cysteine proteinase activities increased
      during senescence. Senescence-induced cysteine proteinase activity was inhibited
      by cysteine, dithiotreitol, or E-64. Senescence-dependent decreases in redox
      active factors, particularly ascorbate and peroxiredoxin favour decreased redox
      mediated inactivation of cysteine proteinases.

PMID- 16455081
TI  - Two motifs essential for nuclear import of the hnRNP A1 nucleocytoplasmic
      shuttling sequence M9 core.
AB  - Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 regulates mRNA genesis. It
      shuttles between the nucleus and cytoplasm. Its shuttling signal is a 38-residue
      sequence M9. We studied the nuclear import and export of M9 by mutational
      analysis. Heterokaryon assay indicated that the 19-residue sequence
      SNFGPMKGGNFGGRSSGPY (M9 core) is necessary and sufficient for shuttling.
      Moreover, M9 core mutation revealed that in addition to the hitherto
      characterized N-terminal motif SNFGPMK, the C-terminal motif PY is crucial for
      nuclear import as well as for binding to transportin. Key residues of the motifs
      are conserved in the shuttling signals of hnRNP D and JKTBP.

PMID- 16455083
TI  - Microtubule binding proteins CLIP-170, EB1, and p150Glued form distinct plus-end
      complexes.
AB  - Microtubule plus-end proteins CLIP-170 and EB1 dynamically track the tips of
      growing microtubules in vivo. Here we examine the association of these proteins
      with microtubules in vitro. CLIP-170 binds tubulin dimers and co-assembles into
      growing microtubules. EB1 binds tubulin dimers more weakly, so no co-assembly is
      observed. However, EB1 binds to CLIP-170, and forms a co-complex with CLIP-170
      and tubulin that is recruited to growing microtubule plus ends. The interaction
      between CLIP-170 and EB1 is competitively inhibited by the related CAP-Gly
      protein p150Glued, which also localizes to microtubule plus ends in vivo. Based
      on these observations, we propose a model in which the formation of distinct plus
      end complexes may differentially affect microtubule dynamics in vivo.

PMID- 16455084
TI  - The effect of high-fat feeding on intramuscular lipid and lipid peroxidation
      levels in UCP3-ablated mice.
AB  - Uncoupling protein-3 (UCP3) has been suggested to protect against lipid-induced
      oxidative damage. Therefore, we studied intramuscular lipid peroxide levels and
      high-fat diet induced alterations in muscle lipid metabolism of UCP3-ablated
      mice. UCP3-/- mice showed approximately 3-fold higher levels of intramuscular
      lipid peroxides upon standard chow feeding, compared to wild-type littermates.
      Remarkably, this difference was no longer apparent on the high-fat diet. However,
      upon high-fat feeding, intramuscular triacylglycerol levels were approximately
      50% lower in UCP3-/- mice, in comparison to UCP3+/+ animals. Succinate
      dehydrogenase activity, and total protein content of the muscle fatty acid
      transporter FAT/CD36 were however similar between UCP3-/- and UCP3+/+ mice.

PMID- 16455085
TI  - Plasma steroid hormones in two Arctic-breeding shorebirds: monogamy versus
      polygyny.
AB  - Steroid hormones are predicted to vary with mating systems, degree of paternal
      care and aggression, as proposed in the "challenge hypothesis." We measured
      plasma concentrations of testosterone (T) and 5alpha-dihydrotestosterone (DHT) in
      two high Arctic breeding and closely related shorebird species, the polygynous
      pectoral sandpiper (Calidris melanotos) and the monogamous semipalmated sandpiper
      (Calidris pusilla) to examine whether the hormonal findings corroborate the
      predictions of the challenge hypothesis. In both species, males showed
      significantly higher levels of DHT and T than females, but in pectoral sandpipers
      median T levels were 34 times greater in males than in females, whereas in
      semipalmated sandpiper there was only a 4.9-fold difference. T and DHT
      concentrations correlated in semipalmated sandpipers and in male, but not in
      female, pectoral sandpipers. In semipalmated sandpipers, androgen levels were
      highest in the beginning of the breeding season and then declined, whereas male
      pectoral sandpipers showed extremely high androgen levels which were sustained
      throughout the breeding season. In both species, androgen levels were independent
      of body condition. Several incubating male semipalmated sandpipers had high
      circulating T levels, suggesting that low T is not required to exhibit paternal
      care. Our results are consistent with the challenge hypothesis in that androgen
      concentrations were higher throughout the breeding season in the polygynous
      compared to the monogamous species. Our study also supports previous studies
      suggesting that the short breeding season in the high Arctic and the importance
      of male care to nest success may be factors leading to behavioral T
      insensitivity.

PMID- 16455086
TI  - Relative effects of estradiol-17beta (E2), catecholestrogens and clomiphene
      citrate on in vitro oocyte maturation in the catfish Heteropneustes fossilis
      (Bloch) and E2 inhibition of 2-hydroxyestradiol-induced maturation.
AB  - In vitro effects of estradiol-17beta (E(2)), the catecholestrogens 2-hydroxyE(2)
      (2-OHE(2)) and 2-methoxyE(2), and the nonsteroidal antiestrogen clomiphene
      citrate (clomid) on oocyte maturation were investigated in the catfish
      Heteropneustes fossilis. Incubation of postvitellogenic follicles with 2-OHE(2)
      induced germinal vesicle breakdown (GVBD; 86% at 5 microM for 30 h) and
      progression of meiosis up to metaphase II, as evident from the presence of
      Hoechst stained metaphase chromosomes and anti-alpha-tubulin-positive bipolar
      spindles. The response was both concentration (1, 2.5, 5, 10, and 20 microM)- and
      duration (0, 3, 6, 12, 24, and 30 h)-dependent. The diameter of the follicles
      increased and about 20% follicles elicited ovulation. Incubation of the follicles
      with clomid (20 microM) induced only about 29-35% GVBD at 30 h. This might be due
      to the dual properties of clomid with estrogenic (cis-isomer) and antiestrogenic
      (trans-isomer) actions or due to estrogen receptor binding dynamics. Incubations
      of the follicles with E(2) or 2-methoxyE(2) did not induce oocyte maturation. The
      higher concentrations of 2-methoxyE(2) caused degenerative changes in the
      follicles. In competition studies, E(2) inhibited the GVBD response of 2-OHE(2)
      (5 microM) significantly in a concentration (1, 5, 10, and 20 microM) or duration
      (2, 4, and 6 h)-dependent manner after pre-incubation with 20 microM E(2)
      (P<0.001, one-way ANOVA, P<0.05, Newman-Keuls' test). The results show that 2
      OHE(2) induces maturational activity while the parent estrogen is a strong
      inhibitor, alone or in combination with 2-OHE(2).

PMID- 16455087
TI  - Sirolimus accelerates senescence of endothelial progenitor cells through
      telomerase inactivation.
AB  - BACKGROUND: Sirolimus-eluting stent (SES) is commonly used to prevent in-stent
      restenosis but is not infrequently complicated by late angiographic stent
      thrombosis (LAST). On the other hand, circulating endothelial progenitor cells
      (EPCs) play a significant role in the maintenance of endothelial integrity. AIM:
      We examined whether sirolimus affects differentiation, proliferative activity,
      senescence, colony formation, and network formation in EPCs originated from
      mononuclear cells (MNCs). METHODS AND RESULTS: MNCs were isolated from peripheral
      blood of healthy volunteers. EPCs outgrew from the culture of MNCs in the
      presence of vascular endothelial growth factor. When MNCs were incubated with
      sirolimus at 0.01, 0.1, and 1 ng/ml for 4 days, sirolimus dose-dependently
      reduced the number of differentiated, adherent EPCs, as assessed by an in vitro
      culture assay. After ex-vivo cultivation, EPCs became senescent as determined by
      acidic beta-galactosidase staining. When MNCs were treated with sirolimus,
      sirolimus dose-dependently accelerated the onset of EPCs senescence. RT-PCR
      analysis demonstrated that FK506-binding protein 12 (FKBP12), a receptor of
      sirolimus, was expressed in MNCs. To obtain an insight into the underlying
      downstream effects of sirolimus, we measured telomerase activity and the
      expression of p27(kip1). Sirolimus decreased telomerase activity dose
      dependently, which was accompanied with down-regulation of the catalytic subunit,
      telomerase reverse transcriptase (TERT). Furthermore, sirolimus up-regulated the
      cell cycle inhibitor p27(kip1). Having demonstrated that sirolimus accelerated
      the onset of senescence, we examined whether that translated into a decrease in
      proliferative activity and clonal expansion. Both MTS assay and BrdU
      incorporation assay have shown that sirolimus treatment significantly diminished
      the proliferative activity in EPCs. In addition, colony forming unit assay
      revealed that sirolimus dramatically decreased colony formation as compared to
      control (no treatment). Finally, in a Matrigel assay, EPCs treated with sirolimus
      were shown to be less integrated into the network formation than control (no
      treatment). CONCLUSION: The inhibitory effects of sirolimus on circulating EPCs
      potently may affect re-endotheliazation after SES implantation.

PMID- 16455088
TI  - Why fine-wire fixators work: an analysis of pressure distribution at the wire
      bone interface.
AB  - Tensioned fine-wire external fixator systems have been used successfully for the
      treatment of fractures, mal-unions and for limb lengthening for many years. When
      used in metaphyseal bone, this type of fixator has a lower loosening rate than
      half-pin fixators. The differing mechanical properties of these fixator systems
      have been investigated extensively; however, most studies have centered on the
      mechanical properties of the fixator as a whole. Our knowledge of the
      interactions occurring at the interface between implant and bone remains sparse.
      In order to investigate this interaction, we devised a simple experimental model
      to characterise the distribution of pressure in cancellous bone surrounding a
      tensioned wire under loading conditions. Comparison was then made to a similar
      model of a half-pin fixator. Pressure was measured using pressure sensitive film
      at various distances away from the implant-bone interface. Static, single cycle
      loading of the model was performed with a Universal Testing Machine. Pressure
      distribution in the fine-wire model was found to occur in three regions: polar,
      beam loading and uniform. Polar patterns were seen closest to the wire with
      pressure concentrated at the entry and exit points of the wire. Beam loading was
      seen at a distance of 1.5 mm from the wire and pressure reached a uniform
      distribution at 4.0 mm. Most of the pressure measured was less than 2 MPa, which
      is less than the yield strength of cancellous bone (2-7 MPa). Higher loads
      produced higher stresses but the distribution pattern was similar. In contrast,
      the half-pin model showed far higher pressures (20 MPa), which were present
      deeper in the bone specimen. These results further our understanding of the
      biomechanics of fine-wire fixators and may explain the lower loosening rate of
      this type of fixator when compared to half-pin fixators used in metaphyseal bone.

PMID- 16455089
TI  - Ambulatory measurement of arm orientation.
AB  - In order to evaluate the impact of neuromuscular disorders affecting the upper
      extremities, the functional use of the arm need to be evaluated during daily
      activities. A system suitable for measuring arm kinematics should be ambulatory
      and not interfere with activities of daily living. A measurement system based on
      miniature accelerometers and gyroscopes is adequate because the sensors are small
      and do not suffer from line of sight problems. A disadvantage of such sensors is
      the cumulative drift around the vertical and the problems with aligning the
      sensor with the segment. A method that uses constraints in the elbow to measure
      the orientation of the lower arm with respect to the upper arm is described. This
      requires a calibration method to determine the exact orientation of each of the
      sensors with respect to the segment. Some preliminary measurements were analyzed
      and they indicated a strong reduction in orientation error around the vertical.
      It seemed that the accuracy of the method is limited by the accuracy of the
      sensor to segment calibration.

PMID- 16455090
TI  - Thin-layer chromatography analysis of fructooligosaccharides in biological
      samples.
AB  - This study presents the application of a rapid, simple and inexpensive thin-layer
      chromatography (TLC) for the analysis of fructooligosaccharides (FOSs) as feed
      additives (prebiotics) in complicated biological samples with minimal pre
      treatment. Prebiotics have been monitored in different parts of the intestinal
      tract (jejunum, ileum and colon) of monogastric animals to which commercially
      available dietetic products containing fructooligosaccharides Raftifeed IPX,
      Raftilose and polysaccharide maltodextrin have been added into the feed. Thereby
      it contributes to a clarification of fructooligosaccharides and polysaccharides
      transformation in the digestive system. Chromatographic separation has been
      studied on different chromatographic systems (stationary and mobile phases).
      Optimal separation of fructooligosaccharides in dietetic products as well as in
      the samples from intestinal tract of monogastric animals has been achieved on
      glass-backed precoated silica gel layers impregnated with sodium acetate. The
      layers were developed with butanol-ethanol-water (5:3:2, v/v) in a vertical
      trough glass chamber with mobile phase vapour saturation. The visualisation of
      FOSs on chromatograms was performed with mixture of diphenylamine-aniline
      phosphoric acid in acetone as primary detection reagent. Coloured spots of FOSs
      (blue-pink spots) on chromatograms have also been detected by reflectance
      densitometry at wavelength lambda=370nm. Simultaneously, the concentration of
      acetic acid, which is one of FOSs fermentation product, was monitored in the
      intestinal contents from jejunum, ileum and colon by capillary isotachophoresis.

PMID- 16455092
TI  - Characterization of a novel continuous supermacroporous monolithic cryogel
      embedded with nanoparticles for protein chromatography.
AB  - A novel continuous supermacroporous monolithic cryogel embedded with nanometer
      size particles was prepared by the radical cryogenic co-polymerization of
      acrylamide (AAm), N,N'-methylene-bis-acrylamide (MBAAm), allyl glycidyl ether
      (AGE) and the dispersed surfactant-stabilized Fe3O4 nanoparticles under the
      freezing-temperature variation condition in a glass column. This special
      separation matrix has interconnected supermacropores with pore size of 10-50
      microm, which permit the free-passage of microbial cells or cell debris in the
      culture fluids and then is interest in downstream processes. The axial liquid
      dispersion coefficients of the new continuous supermacroporous monolithic bed at
      different liquid flow rates were obtained by measuring residence time
      distributions (RTDs) using tracer pulse-response method. The experimental results
      showed that the axial liquid dispersion within the bed was weak in a wide water
      flow rate of 0.5-15 cm/min. The axial dispersion coefficient was found to be
      increased exponentially with the increase of liquid flow rate. Chromatographic
      process of bovine serum albumin (BSA) in the cryogel monolithic bed was carried
      out to reveal the protein breakthrough and elution characteristics. Compared with
      other reported cryogel beds in literature, the protein adsorption capacity of the
      present cryogel bed was improved due to the embedded nano-sized solid adsorbents
      in the gel matrix. Microstructure morphology of the embedded nanoparticles in the
      cryogel and the gel matrix structure were also analyzed by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM) in this paper.

PMID- 16455091
TI  - Determination of microstickies in recycled whitewater by headspace gas
      chromatography.
AB  - This study proposed a novel headspace gas chromatographic (HS-GC) method for
      determination of adhesive contaminants (microstickies) in recycled whitewater, a
      fiber containing process stream, in the paper mill. It is based on the adsorption
      behavior of toluene (as a tracer) on the hydrophobic surface of microstickies,
      which affects the apparent vapor-liquid equilibration partitioning of toluene. It
      was found that the equilibrium concentration of toluene in the vapor phase is
      inversely proportional to the apparent effective surface area of microstickies
      that remain in the corresponding solution. Thus, the amount of microsticky
      materials in the recycled whitewater can be quantified by HS-GC via indirect
      measurement of the toluene content in the vapor phase of the sample without any
      pretreatment. The presented method is simple, rapid and automated.

PMID- 16455093
TI  - Preparation and characteristics of high pH-resistant sol-gel alumina-based hybrid
      organic-inorganic coating for solid-phase microextraction of polar compounds.
AB  - A novel alumina-based hybrid organic-inorganic sol-gel coating was first
      developed for solid-phase microextraction (SPME) from a highly reactive alkoxide
      precursor, aluminum sec-butoxide, and a sol-gel-active organic polymer hydroxyl
      terminated polydimethylsiloxane (OH-TSO). The underlying mechanism was discussed
      and confirmed by IR spectra. The porous surface structure of the sol-gel coating
      was revealed by scanning electron microscopy. A detailed investigation was
      conducted to evaluate the remarked performance of the newly developed sol-gel
      alumina-OH-TSO hybrid materials. In stark contrast to the sol-gel silica-based
      coating, the alumina-based coating demonstrated excellent pH stability. In
      addition, good thermal resistance and coating preparation reproducibility are
      also its outstanding performance. As compared to silica-based hybrids material,
      the ligand exchange ability of alumina makes it structurally superior extraction
      sorbents for polar compounds, such as fatty acids, phenols, alcohols, aldehydes
      and amines. Practical applicability of the prepared alumina-OH-TSO fiber was
      demonstrated through the analysis of volatile alcohols and fatty acids in beer.
      The recoveries obtained ranged from 85.7 to 104% and the relative standard
      deviation values for all analytes were below 9%.

PMID- 16455094
TI  - Hot-water and solid-phase extraction of fluorescent whitening agents in paper
      materials and infant clothes followed by unequivocal determination with ion-pair
      chromatography-tandem mass spectrometry.
AB  - A comprehensive method for the determination of four stilbene-type disulfonate
      and one distyrylbiphenyl-type fluorescent whitening agents (FWAs) in paper
      materials (napkin and paper tissue) and infant clothes was developed. FWAs were
      extracted from paper material and cloth samples using a hot-water extraction, and
      the aqueous extracts were then preconcentrated with the newly developed Oasis WAX
      (mixed-mode of weak anion exchange and reversed-phase sorbent) solid-phase
      extraction cartridge. The analytes were unequivocal determined by ion pair
      chromatography coupled with negative electrospray ionization-tandem mass
      spectrometry (HPLC-ESI-MS-MS), applying a di-n-hexyl-ammonium acetate (DHAA) as
      the ion-pairing reagent in mobile phase. Limits of quantitation (LOQ) were
      established between 0.2 and 0.9 ng/g in 2 g of samples. Recovery of five FWAs in
      spiked commercial samples was between 42 and 95% and RSD (n = 3) ranging from 2
      to 11%. The method was finally applied to commercial samples, showing that two
      stilbene-type disulfonates were predominant FWAs detected in napkin and infant
      cloth samples.

PMID- 16455095
TI  - Microemulsion mediated in situ derivatization-extraction and gas chromatography
      mass spectrometric analysis of alkylphosphonic acids.
AB  - Detection and identification of environmental signatures of chemical warfare
      agents is an important aspect of verification program of Chemical Weapons
      Convention (CWC). Alkylphosphonic acids (APAs) are ultimate and persistent
      degradation products of nerve agents. Their identification in a sample submitted
      for off-site analysis infers possible indication of contamination with nerve
      agents. This paper describes the development of a new sample preparation method
      which involves 'in situ derivatization and extraction' (INDEX) of acids from
      water. Derivatization is performed by alkylation of APAs with alkylbromides in
      surfactant less microemulsion (SLME). The derivatized analytes were analyzed by
      gas chromatography coupled with mass spectrometry. The developed method involves
      simultaneous derivatization (alkylation) and extraction of acidic analytes
      mediated by surfactant less microemulsion. Various derivatization-extraction
      parameters such as solvent, reaction time and temperature, base and alkyl
      bromides were optimized. Pentyl bromide in the presence of potassium carbonate
      and diisopropylamine at 100 degrees C derivatized the selected acids efficiently.
      Kinetic data for alkylation of methylphosphonic acids and some carboxylic acids
      were obtained to assess their relative susceptibility for alkylation in
      microemulsion. Methylphosphonic acid and isopropyl methylphosphonic acid took 140
      150 min to reach completion while carboxylic acids took 100 min to complete the
      reaction. INDEX could be successfully performed even in the presence of
      interfering Ca(2+) and Mg(2+) ions.

PMID- 16455096
TI  - Incorporation of flow injection analysis or capillary electrophoresis with
      resonance Rayleigh scattering detection for inorganic ion analysis.
AB  - Resonance Rayleigh scattering (RRS) has been explored as a detection (RRSD)
      technique for capillary electrophoresis (CE) or flow injection analysis (FIA) of
      inorganic ions. The detection was achieved through a scattering probe of ion
      association complex formed from rhodamine B (Rh B) and iodine. The probe scatters
      strongly at 630 nm when oxidants such as Cr(2)O(7)(2-), MnO(4)(-) and ClO(-)
      present in a mixed solution of Rh B and iodide. The scattering disappears once
      iodine is reduced by reductants. Oxidant or reductant species in a sample can
      thus be detected by positive or negative RRS signal. To verify the RRSD, FIA-RRSD
      was first constructed and continuous measurement of testing samples containing
      Cr(2)O(7)(2-), MnO(4)(-) and/or ClO(-) was performed. The detection limits
      reached a level of decade nM and a linear range was found between peak height and
      concentration at the range of 0.255-2.04microM for Cr(2)O(7)(2-), 0.158
      3.16microM for MnO(4)(-), and 1.18-9.43microM for ClO(-), with linear regression
      coefficients of all above 0.99. The run-to-run relative standard deviation of
      peak height was less than 3% (n=6). CE-RRSD was then set up and studied, using a
      capillary of 75microm i.d.x33cm filled with a running buffer of 50mM citrate and
      25mM Tris (pH 3.32) and worked under -12kV at room temperature. The CE eluent was
      at-line conducted into a stream of rhodamine B and iodine flowing inner a wide
      tube by plugging the capillary outlet into the wide tube. Different mixtures
      prepared from Cr(2)O(7)(2-), MnO(4)(-) and ClO(-) were successfully separated and
      detected by the CE-RRSD.

PMID- 16455097
TI  - Gas-liquid chromatographic method for analysing complex mixtures of fatty acids
      including conjugated linoleic acids (cis9trans11 and trans10cis12 isomers) and
      long-chain (n-3 or n-6) polyunsaturated fatty acids. Application to the
      intramuscular fat of beef meat.
AB  - The optimisation and validation of a gas-liquid chromatographic (GLC) method
      using direct saponification with KOH/methanol followed by a derivatization with
      (trimethylsilyl)diazomethane was carried out trying to overcome all the
      difficulties posed by the analysis of complex mixtures of fatty acids (FAs) in
      animal fat tissues. The presented method allowed sensitive, selective and
      simultaneous determination of a wide range of different FAs, including short
      chain FAs, branched-chain FAs and conjugated linoleic acid isomers in the same
      GLC run along with other well known saturated, monounsaturated and
      polyunsaturated FAs. To demonstrate the feasibility of the procedure, the total
      FA profile of beef meat was characterised.

PMID- 16455098
TI  - Cross-condensation and particle growth in aqueous silane mixtures at low
      concentration.
AB  - We have observed the condensation of a mixture of gamma
      glycidoxypropylmethyldiethoxysilane and 3-aminopropyltriethoxysilane in dilute
      aqueous solutions. NMR and IR spectroscopy have allowed to follow the
      condensation process in the mixture, which is noticeably enhanced and proceeds
      faster than for each silane on its own. Cross-condensation between the two
      silanes was evidenced. When the hydrophilic aminosilane is in excess, the
      condensation, as evidenced by dynamic light scattering, proceeds toward gel
      formation because the oligomers formed are essentially hydrophilic. When the more
      hydrophobic epoxysilane is in excess, oligomer growth proceeds slowly and results
      in a destabilization of the solution: due to their hydrophobic character, the
      oligomers formed coalesce suddenly into 200-nm-diameter aggregates. Coatings
      deposited from such solutions with high epoxysilane content can be used to
      strengthen glass. We show that the progress of condensation in solution results
      in a wetting transition during deposition of the silane film on glass by dip
      coating. The production of increasingly hydrophobic oligomers as the reaction
      time increases results in adsorption of more hydrophobic aggregates at the
      surface, which eventually leads to dewetting of the film: in the absence of film,
      glass strengthening disappears.

PMID- 16455099
TI  - Preparation and characterization of monovalent cation selective sulfonated
      poly(ether ether ketone) and poly(ether sulfone) composite membranes.
AB  - Highly charged cation permeable composite membranes were prepared by blending of
      sulfonated poly(ether sulfone) (SPES) with sulfonated poly(ether ether ketone)
      (SPEEK) in 0 to 90% weight ratio, to adjust the hydrophobic properties and ion
      selective nature. Extent of sulfonation was confirmed by 1H NMR and ion exchange
      capacity and degree of sulfonation depending on blending composition. These
      membranes were characterized as a function of weight fraction of SPEEK by
      recording ion-exchange capacity, water uptake, thermogravimetric analysis,
      membrane conductivity and membrane potential in equilibration with different
      electrolytic solutions. Membrane permselectivity and solute flux were estimated
      using these data on the basis of non-equilibrium thermodynamic principles and for
      observing the selectivity of different membranes for mono- or bivalent counter
      ions. It was observed that relative selectivity for monovalent in comparison to
      bivalent counter-ions were increased with the decrease in SPEEK content in the
      composite membrane matrix. The range of SPEEK content in the blend from 60 to 80%
      appears the most suitable for the selective separation of monovalent ions from
      bivalent ions. Furthermore, highly charged nature and stabilities of these
      membranes extend their applications for the electro-assisted separations of
      similarly charged ions as well as other electro-membrane processes.

PMID- 16455100
TI  - Organic dye molecules as reducing agent for the synthesis of electroactive gold
      nanoplates.
AB  - Highly crystalline, hexagonal and triangular nanoplates of gold are synthesized
      in high yield by a new wet chemical method using multifunctional molecules,
      Bismarck brown R (BBR) and Bismarck brown Y (BBY). This method involves a simple
      approach by keeping a mixture of aqueous HAuCl4 solution and BBR/BBY solution in
      presence of poly(vinyl pyrrolidone) for 24 h. These nanostructures show
      unprecedented electrochemical properties exhibiting surface confinement effect.
      The UV-visible (UV-vis) spectrum shows certain distinct features with absorptions
      at 300, 400, and 650 nm extending up to the near infrared region. Selected area
      electron diffraction patterns of these nanoparticles show highly oriented (111)
      crystal facets. X-ray diffraction analysis also confirms the predominant
      orientation in the (111) crystal planes with lattice constant approximately 4.07
      angstroms of face-centered-cubic (fcc) gold. X-ray photoelectron (XP) and Fourier
      transform infrared (FTIR) spectroscopic analysis shows the presence of a fraction
      of reducing molecules as surface passivating agent either in the unreacted
      molecular state or as a mixture of reacted and unreacted product, which probably
      undergoes charge transfer with gold nanocrystals giving absorption at
      approximately 300 nm.

PMID- 16455101
TI  - A comparison of JKR-based methods to analyze quasi-static and dynamic indentation
      force curves.
AB  - The Johnson-Kendall-Roberts (JKR) theory of elastic contact, extended to take
      viscoelastic effects into account, is used to evaluate work of adhesion and
      modulus of elastomeric films. In this paper, we present a comparison of five
      approaches to analyze quasi-static and dynamic JKR force curve data obtained
      using instrumented indentation. The load-displacement experiments were performed
      using a 200-microm radius borosilicate glass sphere against poly(dimethyl
      siloxane) (PDMS). By applying a small oscillation to the tip during indentation,
      dynamic stiffness vs load data were also obtained for frequencies between 25 and
      160 Hz. Direct curve fitting as well as simplified 2- and 3-point analysis
      methods were used to compare modulus values obtained from load-displacement and
      stiffness-load data. Fit methods not requiring determination of the initial point
      of tip-sample contact ("zero" displacement) provided modulus values closest to
      those obtained by direct curve fitting. The dynamic stiffness-load data revealed
      a frequency dependent modulus; load-displacement measurements obtained
      simultaneously were consistent with the relaxed, or low-frequency, modulus of the
      PDMS sample. These experiments demonstrate that both the frequency dependent and
      relaxed modulus can be obtained from a single experiment.

PMID- 16455102
TI  - Phosphate adsorption on synthetic goethite and akaganeite.
AB  - Low crystalline iron hydroxides such as goethite (alpha-FeOOH) and akaganeite
      (beta-FeOOH) were synthesized, and the selective adsorption of phosphate ions
      from phosphate-enriched seawater was examined. The results of the distribution
      coefficients (K(d)) of oxoanions in mixed anion solutions at pH 8 follow the
      selectivity order Cl-, NO3-, SO4(2-) << CO3(2-), HPO4(2-) for goethite, and Cl-,
      CO3(2-) < NO3- < SO4(2) << HPO4(2-) for akaganeite. In seawater, both adsorbents
      show high selectivity for phosphate ions despite the presence of large amounts of
      major cations and anions in seawater. The adsorption isotherms fitted better with
      the Freundlich equation and the maximum uptake of phosphate from phosphate
      enriched seawater was 10 mg P/g at an equilibrium phosphate concentration of 0.3
      mg P/L on both adsorbents. The phosphate adsorption/desorption cycles show that
      akaganeite is an excellent adsorbent even after 10 cycles and its chemical
      stability is good.

PMID- 16455103
TI  - Identification of traits associated with stuttering.
AB  - Stuttering has been considered a heritable disorder since the 1930s. There have
      been different models of transmission that have been proposed most involving a
      polygenic component with or without a major locus. In spite of these models, the
      characteristics being transmitted are not known. This study used two different
      tasks-a tapping task that is thought to probe hemispheric differences and a
      Stroop task, which appears to create interferences in speech motor programming
      and/or execution. The 48 participants in this study included individuals who
      stutter, high risk family members and controls for each group. Results indicated
      that for tapping at a comfortable rate, the experimental groups were
      significantly different from their control groups and for tapping at a fast rate,
      the stuttering and high risk groups were different from each other. The results
      of the Stroop test were not statistically significant. LEARNING OUTCOMES: Readers
      will learn about: (1) genetic aspects of stuttering; (2) hemispheric dominance in
      stuttering and high risk subjects; (3) understanding traits that may be
      associated with stuttering.

PMID- 16455104
TI  - A whole blood assay to assess peripheral blood dendritic cell function in
      response to Toll-like receptor stimulation.
AB  - We report a practical technique to assess peripheral blood dendritic cell (DC)
      maturation and function in whole blood (WB), which requires minimal blood volumes
      and minimizes ex vivo manipulations of clinical specimens. We determined optimal
      conditions for flow cytometric analysis of markers of DC maturation, including
      CCR7, CD25, CD80 and CD83, and of the intracellular cytokines, tumor necrosis
      factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha), in both myeloid (mDC)
      and plasmacytoid (pDC) lineages. We demonstrate concentration-dependent
      production of these cytokines by DC following short-term stimulation with ligands
      to Toll-like receptors (TLRs) 2/1, 3, 4, 7, 8 and 9. Kinetic studies revealed
      maximal TNF-alpha and IFN-alpha protein expression at 2 to 3 h after stimulation
      with certain TLR ligands. Finally, utilizing cells from a cohort of eight healthy
      donors, we compared DC responses to TLR activation in WB, freshly isolated
      peripheral blood mononuclear cells (PBMC) and cryopreserved PBMC. We found that
      TNF-alpha responses were essentially preserved, but IFN-alpha responses were
      profoundly diminished or entirely abrogated following cryopreservation. In
      conclusion, we propose that WB analysis of peripheral DC function is a rapid,
      reliable and simple method to evaluate TLR function in clinical specimens, which
      obviates artifact-prone cell purification. The major impact of cryopreservation
      on some DC responses further strengthens the case for a rapid method that uses
      fresh blood.

PMID- 16455105
TI  - An investigation of hypothalamic-pituitary-adrenal axis hyperactivity in anorexia
      nervosa: the role of CRH and AVP.
AB  - We hypothesised that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in
      anorexia nervosa (AN) is associated with (a) elevated arginine vasopressin (AVP)
      activity and (b) enhanced pituitary sensitivity to AVP, as it is in depressive
      illness. 16 Healthy women and 18 women with active AN participated in a combined
      dexamethasone (DXM)/corticotrophin releasing hormone (CRH) challenge test and an
      AVP challenge test. This combination of tests is designed to assess the
      functional contribution of AVP to HPA axis activity. 10 of the active AN group
      repeated participation after weight gain. The cortisol response to AVP was
      reduced by 138% in the active AN group, suggesting an impairment of pituitary
      sensitivity to AVP, which began to normalise with weight gain. The cortisol and
      adreno-corticotrophin (ACTH) responses to the DXM/CRH test were not significantly
      enhanced in the active AN group, suggesting that there was no elevated endogenous
      AVP activity augmenting the response to CRH in AN. Weight gain was associated
      with blunting of the endocrine response to the DXM/CRH test, which may have been
      related to rising oestrogen levels. Thus, contrary to the hypotheses, we did not
      find (a) evidence of upregulated AVP activity or (b) enhanced pituitary
      sensitivity to AVP in AN. These findings suggest that the mechanism of HPA axis
      hyperactivity differs in depression and AN, with greater involvement of AVP in
      depressive disorder and perhaps more reliance on CRH to drive the axis in AN. The
      powerful anorexigenic effect of CRH could contribute to the severity of weight
      loss associated with AN.

PMID- 16455106
TI  - Apolipoprotein A-I/apolipoprotein B ratio and aggression in violent and
      nonviolent young adult males.
AB  - Epidemiological, clinical, and experimental studies have linked low or lowered
      cholesterol levels to aggressive behavior. However, no study has measured the
      relationship between aggression and apolipoprotein A-I/apolipoprotein B ratio, a
      robust indicator of cardiac risk. Plasma levels of total cholesterol, HDL-C, LDL
      C, triglycerides, apolipoprotein A-I, and apolipoprotein B were measured and
      correlated with Aggression Questionnaire ratings in 20 young adult males with
      personality disorders and/or a high propensity toward aggressive behavior and in
      40 control subjects. Compared with the control subjects, the subjects in the
      aggressive group had lower levels of apo A-I and a lower apo A-I/apo B ratio.
      Whereas in the control subjects, higher levels of aggression were correlated with
      lower levels of atherogenic lipoproteins (LDL-C and apo B), in the aggressive
      subjects higher levels of aggression were correlated with lower levels of anti
      atherogenic lipoproteins (HDL-C and apo A-I) and higher levels of LDL-C. The
      results of this study confirm the existence of a relationship between blood
      lipids and aggressive behavior in young adult males and suggest that the apo A
      I/apo B ratio might be an additional marker in the search for biological
      correlates of increased risk of violence.

PMID- 16455107
TI  - A tribute to Jack Petajan's inspiration: from goat to goat.
AB  - Development of clinical neurophysiology, especially in neuromuscular disease
      investigation in the 20th century underscores the careers of two academic
      physician-investigators. Experimental models of neuromuscular disorders (toxic
      and diabetic neuropathies, myasthenia gravis, nerve transplant and repair) with
      emphasis on regeneration are described. Subsequent clinical application has
      validated the animal studies. The value of disease related support societies
      (Muscular Dystrophy, Charcot Marie Tooth and Myasthenia Gravis) is discussed, not
      only for patient information and support but also for support of research
      projects and clinical research fellowship training. The clinician-teacher
      investigator as a role model is mentioned, particularly in relation to Dr. Jack
      Petajan's career, a truly renaissance man. Credit is given to the great teachers
      of clinical neurophysiology and neuromuscular diseases of the past 50 years.

PMID- 16455108
TI  - Mechanisms underlying the relaxation induced by isokaempferide from Amburana
      cearensis in the guinea-pig isolated trachea.
AB  - The present study examines possible mechanisms by which the flavonoid
      isokaempferide (IKPF; 5,7,4'-trihydroxy-3-methoxyflavone) from Amburana
      cearensis, a Brazilian medicinal plant popularly used as bronchodilator, induces
      relaxation of guinea-pig isolated trachea. In the trachea (with intact
      epithelium) contracted by carbachol, IKPF (1-1000 microM) caused a graded
      relaxation, and the epithelium removal increased the sensitivity of the airway
      smooth muscle to IKPF (EC50, in intact tissue: 77.4 [54.8-109.2] microM; in
      denuded epithelium: 15.0 [11.3-20.1] microM). The IKPF-induced relaxation was
      inhibited in 41% by the nitric oxide (NO) synthase inhibitor L-NAME (100 microM);
      in 31% and 50% by the soluble guanylate cyclase (sGC) inhibitor ODQ (3 and 33
      microM); by propranolol (31%) and also by capsaicin (37%). In the trachea pre
      contracted by 40 mM KCl the pre-incubation with glibenclamide (33 microM) or
      iberiotoxin (IbTX, 0.1 microM), selective K(+) channel inhibitors, inhibited the
      IKPF-induced relaxation by 39% and 38%, respectively. On the other hand, 4
      aminopyridine (100 microM), a nonselective K(+) channel antagonist, did not
      significantly influence the effect of IKPF, while IbTX induced a rightward
      displacement of the IKPF concentration-response curve. However, in muscle pre
      contracted with 120 mM KCl the relaxant effect of IKPF was significantly reduced
      and not affected by glibenclamide. In conclusion, these results indicate a direct
      and epithelium-independent relaxant effect of IKPF on smooth muscle fibers.
      Although this IKPF relaxant action seems to be multi-mediated, it occurs via both
      Ca(2+) and ATP-sensitive K(+) channels, but some other possible mechanisms
      unrelated to K(+) channels cannot be excluded.

PMID- 16455109
TI  - Flavonoid-drug interactions: effects of flavonoids on ABC transporters.
AB  - Flavonoids are present in fruits, vegetables and beverages derived from plants
      (tea, red wine), and in many dietary supplements or herbal remedies including
      Ginkgo Biloba, Soy Isoflavones, and Milk Thistle. Flavonoids have been described
      as health-promoting, disease-preventing dietary supplements, and a high intake of
      flavonoids has been associated with a reduced risk of cancer, cardiovascular
      diseases, osteoporosis and other age-related degenerative diseases. Due to an
      increased public interest in alternative medicine and disease prevention, the use
      of herbal preparations containing high doses of flavonoids for health maintenance
      has become very popular, raising the potential for interactions with conventional
      drug therapies. This review will summarize the current literature regarding the
      interactions of flavonoids with ATP-binding cassette (ABC) efflux transporters,
      mainly P-glycoprotein, MRP1, MRP2 and BCRP and discuss the potential consequences
      for flavonoid-drug transport interactions.

PMID- 16455110
TI  - Role of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the
      regulation of blood pressure by leptin in lean and obese rats.
AB  - We investigated the role of nitric oxide (NO) and endothelium-derived
      hyperpolarizing factor (EDHF) in hemodynamic action of leptin. The effect of
      leptin (1 mg/kg i.p.) on systolic blood pressure (SBP) was examined in lean rats
      and in rats made obese by feeding highly palatable diet for either 1 or 3 months.
      Separate groups received NO synthase inhibitor, L-NAME, or EDHF inhibitors, the
      mixture of apamin+charybdotoxin or sulfaphenazole, before leptin administration.
      Leptin increased NO production, as evidenced by increase in plasma and urinary NO
      metabolites and cyclic GMP. This effect was impaired in both obese groups. In
      lean rats either leptin or EDHF inhibitors had no effect on blood pressure. L
      NAME increased blood pressure in lean animals and this effect was prevented by
      leptin. However, when leptin was administered to animals pretreated with both L
      NAME and EDHF inhibitors, blood pressure increased even more than after L-NAME
      alone. In the 1-month obese group leptin had no effect on SBP, however, pressor
      effect of leptin was observed in animals pretreated with EDHF inhibitors. In the
      3-month obese group leptin alone increased SBP, and EDHF inhibitors did not
      augment its pressor effect. The results suggest that leptin may stimulate EDHF
      when NO becomes deficient, e.g. after NOS blockade or in short-term obesity.
      Although the effect of leptin on NO production is impaired in the 1-month obese
      group, BP does not increase, probably because EDHF compensates for NO deficiency.
      In contrast, leptin increases BP in 3-month obesity because its effect on EDHF is
      also attenuated.

PMID- 16455111
TI  - Growth inhibitory effect of quercetin on SW 872 human liposarcoma cells.
AB  - Adipocytic tumors represent the largest single group of soft tissue tumors. In
      the present study, we investigated the antiproliferative potential of quercetin
      in SW 872 human liposarcoma cells. Cell viability was significantly influenced by
      quercetin treatment in a time- and dose-dependent manner. Flow cytometric
      analyses of SW 872 human liposarcoma cells exposed to quercetin showed that the
      increase of apoptotic cells was time- and dose-dependent. The percentages of
      normal cells were decreased and apoptotic cells (including early apoptotic and
      late apoptotic) were increased with increasing concentrations of quercetin.
      Quercetin-induced apoptosis in SW 872 human liposarcoma cells was associated with
      the loss of mitochondrial membrane potential (DeltaPsi(m)). The apoptosis in SW
      872 human liposarcoma cells induced by quercetin was mediated through the
      activation of caspase-3, Bax, and Bak and then cleavage of PARP and
      downregulation of Bcl-2. These results demonstrate that quercetin may prevent
      atypical lipomatous tumors/well-differentiated liposarcomas from mature
      adipocytic proliferation, which may contribute to its antiproliferative function.

PMID- 16455112
TI  - Effect of predator density dependent dispersal of prey on stability of a predator
      prey system.
AB  - This work presents a predator-prey Lotka-Volterra model in a two patch
      environment. The model is a set of four ordinary differential equations that
      govern the prey and predator population densities on each patch. Predators
      disperse with constant migration rates, while prey dispersal is predator density
      dependent. When the predator density is large, the dispersal of prey is more
      likely to occur. We assume that prey and predator dispersal is faster than the
      local predator-prey interaction on each patch. Thus, we take advantage of two
      time scales in order to reduce the complete model to a system of two equations
      governing the total prey and predator densities. The stability analysis of the
      aggregated model shows that a unique strictly positive equilibrium exists. This
      equilibrium may be stable or unstable. A Hopf bifurcation may occur, leading the
      equilibrium to be a centre. If the two patches are similar, the predator density
      dependent dispersal of prey has a stabilizing effect on the predator-prey system.

PMID- 16455113
TI  - TMS in the parietal cortex: updating representations for attention and action.
AB  - Transcranial magnetic stimulation (TMS) is one of the most recent techniques to
      have been used in investigations of the parietal cortex but already a number of
      studies have employed it as a tool in investigations of attentional and
      sensorimotor processes in the human parietal cortices. The high temporal
      resolution of TMS has proved to be a particular strength of the technique and the
      experiments have led to hypotheses about when circumscribed regions of parietal
      cortex are critical for specific attentional and sensorimotor processes. A
      consistent theme that runs through many reports is that of a critical
      contribution of parietal areas when attention or movements are re-directed and
      representations for attention or action must be updated.

PMID- 16455114
TI  - Effects of sex, hindpaw injection site and stimulus modality on nociceptive
      sensitivity in arthritic rats.
AB  - Injection of Complete Freund's adjuvant (CFA) into the hindpaw produces
      inflammation and alterations in nociceptive sensitivity. The present study was
      designed to compare the effects of CFA injection into the dorsal and plantar
      surfaces of the hindpaw on nociceptive sensitivity of the hindpaw to mechanical
      pressure, warm-water and a hotplate stimulus in male and female rats. CFA or
      vehicle (VEH) was injected into the dorsal or plantar surface of the right
      hindpaw on day 0 and tests were conducted on days 4, 6, 8, 10, 11 and 18. Up
      until day 11 the inflammation was confined to the injected hindpaw (monoarthritic
      state), whereas by day 18 both hindpaws were inflamed (polyarthritic state). The
      site of the CFA injection had minimal effects on thermal or mechanical
      sensitivity with the following exceptions. On days 11 and 18 males had higher
      hotplate latencies when injected in the dorsal as compared to the plantar
      surface. For both males and females, warm-water paw withdrawal latencies were
      longer in those rats injected in the dorsal versus the plantar surface on day 18.
      No sex differences in paw pressure thresholds were observed on days 11 and 18 in
      CFA-treated rats. In the warm-water paw withdrawal test CFA-treated males
      exhibited longer latencies than CFA-treated females on day 11, but similar
      latencies on day 18. In the hotplate test CFA-treated females exhibited shorter
      latencies than CFA-treated males on days 11 and 18. The present results
      demonstrate that nociceptive sensitivity is the result of the interplay among
      sex, CFA injection site (plantar vs. dorsal), arthritic state (mono- vs.
      polyarthritic) and stimulus modality (mechanical vs. thermal).

PMID- 16455115
TI  - Behavioral indicators of stress-coping style in rainbow trout: Do males and
      females react differently to novelty?
AB  - It is becoming increasingly clear that individual differences in the behavioral
      response to stressful situations are associated with distinct physiological
      profiles, and stress coping characteristics are of fundamental importance to
      fitness and life history. Teleost fishes display considerable variation in
      reproductive strategy, but sex differences in stress-coping style have not been
      described previously in fish. Prior to sexual maturation, the glucocorticoid
      response to stress is not affected by sex in salmonid fish. Nevertheless,
      behavior in novel and stressful situations differed between immature male and
      female rainbow trout (Oncorhynchus mykiss). When tested 1 week following
      transport to a new rearing facility, females resumed feeding after transfer to
      social isolation quicker than males. The locomotor response to acute confinement
      stress also varied between sexes, with females settling down and ceasing to move
      in a panic-like manner quicker than males. There was a strong correlation between
      behavior in the two test situations: individuals that readily resumed feeding
      behavior in a new environment also moved less in the acute stress test. Thus, the
      time to resume feeding after a stressful experience is a precise indicator of
      stress-coping style in salmonid fish, which is likely to reflect the dynamics of
      neuroendocrine stress responses. Furthermore, these observations could reflect a
      sex difference in the response to novel and stressful situations, which occur
      even in the absence of differences in glucocorticoid responsiveness.

PMID- 16455116
TI  - Substrate specificity of acyl-Delta(6)-desaturases from Continental versus
      Macaronesian Echium species.
AB  - Echium (Boraginaceae) species from the Macaronesian islands exhibit an unusually
      high level of gamma-linolenic acid (18:3n-6; GLA) and relatively low content of
      octadecatetraenoic acid (18:4n-3; OTA) in the seed, while the amounts of both
      fatty acids in their Continental (European) relatives are rather similar. We have
      tested the hypothesis of whether a different specificity of the acyl-Delta(6)
      desaturases (D6DES) towards their respective usual substrates, linoleic acid
      (18:2n-6; LA) for GLA and alpha-linolenic acid (18:3n-3; ALA) for OTA, was partly
      responsible for this composition pattern. To this aim we have expressed in yeast
      the coding sequences of the D6DES genes for the Continental species Echium
      sabulicola, and the Macaronesian Echium gentianoides. When the yeast cultures are
      supplemented with the two fatty acid substrates (LA and ALA), a similar
      utilization of both compounds was found for the D6DES of E. sabulicola, while a
      preference for LA over ALA was observed for the enzyme of E. gentianoides. This
      substrate preference must contribute to the increased accumulation of GLA in the
      seeds of the Macaronesian Echium species. Comparison among the amino acid
      sequences of these desaturases and other related enzymes, allowed us the
      discussion about the possible involvement of some specific positions in the
      determination of substrate specificity.

PMID- 16455117
TI  - Lilac alcohol epoxide: a linalool derivative in Actinidia arguta flowers.
AB  - Lilac alcohol epoxide (2-(5-methyl-5-(oxiran-2-yl)-tetrahydrofuran-2-yl)propan-1
      ol), a previously unreported monoterpene, was identified in the solvent extract
      of the flowers of seven Actinidia arguta genotypes. The diastereomeric lilac
      alcohol epoxides co-occurred with the lilac aldehydes and alcohols. Another
      compound, the lilac diol (2-(5-(1-hydroxyethyl)-5-methyl-tetrahydrofuran-2
      yl)propan-1-ol) was synthesised as part of our efforts to identify the lilac
      alcohol epoxide.

PMID- 16455118
TI  - The malaria and typhoid fever burden in the slums of Kolkata, India: data from a
      prospective community-based study.
AB  - Recent research has indicated that the malaria burden in Asia may have been
      vastly underestimated. We conducted a prospective community-based study in an
      impoverished urban site in Kolkata, India, to estimate the burden of malaria and
      typhoid fever and to identify risk factors for these diseases. In a population of
      60452 people, 3605 fever episodes were detected over a 12-month period. The blood
      films of 93 febrile patients contained Plasmodium (90 P. vivax, 2 P. falciparum
      and 1 P. malariae). Blood cultures from 95 patients grew Salmonella enterica
      serotype Typhi. Malaria patients were found to be significantly older (mean age
      29 years) compared with patients with typhoid fever (15 years; P<0.001) but had
      similar clinical features on presentation. Having a household member with
      malaria, illiteracy, low household income and living in a structure not built of
      bricks were associated with an increased risk for malaria. Having a household
      member with typhoid fever and poor hygiene were associated with typhoid fever. A
      geographic analysis of the spatial distribution of malaria and typhoid fever
      cases detected high-risk neighbourhoods for each disease. Focal interventions to
      minimise human-vector contact and improved personal hygiene and targeted
      vaccination campaigns could help to prevent malaria and typhoid fever in this
      site.

PMID- 16455119
TI  - Can community health workers and caretakers recognise pneumonia in children?
      Experiences from western Uganda.
AB  - Acute respiratory infections (ARI) are leading killers of children. Case
      management using community health workers (CHW) has halved ARI mortality in
      children in Asia. WHO/UNICEF recommend integrating pneumonia into Home Management
      of Malaria strategies. However, in sub-Saharan Africa, CHW's performance to
      recognise pneumonia is rarely demonstrated. We evaluated the ability of CHWs to
      assess rapid breathing in under 5 year olds and explored caretaker interpretation
      of pneumonia symptoms. Ninety-six CHWs were evaluated for their skills to count
      and classify breathing rate in inpatient children. Respiratory illness concepts
      and actions were obtained from focus group discussions with mothers, video
      probing and key informant interviews. Of the CHW assessments, 71% were within +/
      5 breaths/min from the gold standard. The sensitivity of CHW classification was
      75% and the specificity was 83%. Many local terms existed for ARIs, such as
      "quick breathing" and "groaning breathing". There was consistency in the
      interpretation of severity, cause and treatment, most being related to fever and
      treated with antimalarials. Given the ability of CHWs to classify pneumonia,
      their skills should be tested in real life. To minimise failure to treat and
      overtreatment, context-specific communication strategies that improve care
      seeking and increase illness prevalence among patients assessed by CHWs are
      needed. A toolkit including a set of methods for this purpose is proposed.

PMID- 16455121
TI  - Relapsing fever in a traveller from Senegal: determination of Borrelia species
      using molecular methods.
AB  - We describe a case of a febrile patient returning from Senegal in which
      haemoscopic and molecular investigation confirmed tick-borne relapsing fever
      (TBRF), suggesting Borrelia crocidurae as the causative agent. This case
      emphasises the need to include TBRF in the differential diagnosis of fever
      following a journey from endemic countries, including malarial areas.

PMID- 16455120
TI  - Leishmania infantum-induced primary and challenge infections in rhesus monkeys
      (Macaca mulatta): a primate model for visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) was experimentally induced in rhesus macaques (Macaca
      mulatta) by intravenously inoculating 2 x 10(7)amastigotes/kg of body weight of
      Leishmania infantum. The macaques developed a systemic disease showing
      characteristic features of human VL such as fever, diarrhoea, body weight loss,
      anaemia, hypergammaglobulinaemia and transient lymphocytosis, as well as lymph
      node, liver and/or spleen enlargement. Nine weeks after infection, one primate
      showed pronounced weight loss, became moribund and was euthanized. The necropsy
      findings included granulomas composed of parasite-containing macrophages,
      lymphocytes and plasma cells in the liver, spleen and lymph nodes. The remaining
      macaques had a sustained course of infection but developed a mild-to-moderate
      illness that subsequently showed evidence of self-cure. Of note, pathological
      findings included a typical cell-mediated immunity-induced granulomatous reaction
      that had an effect on the control of parasite replication. All infected monkeys
      responded with increased production of anti-Leishmania-specific IgG antibodies.
      Despite the fact that clinical resistance to L. infantum was not consistently
      associated with a parasite-specific cell-mediated immune response, drug-cured
      macaques from the primary infection acquired immunity to homologous re-infection.
      These findings point to the feasibility of using the L. infantum macaque model
      for pre-clinical evaluation of novel chemotherapeutics or vaccine candidates for
      human VL.

PMID- 16455122
TI  - Treatment and follow-up of the first case of human trypanosomiasis caused by
      Trypanosoma evansi in India.
AB  - The first reported human case of trypanosomiasis caused by Trypanosoma evansi was
      treated using suramin. Patient follow-up indicates that the drug and specific
      regimen used were well tolerated. Clinical, serological and parasitological
      investigations at 6 months indicate complete cure of the patient. Suramin should
      be considered in the treatment of other cases of human T. evansi infection, if
      they occur.

PMID- 16455123
TI  - Molecular docking simulations of steroid substrates into human cytosolic
      hydroxysteroid dehydrogenases (AKR1C1 and AKR1C2): insights into positional and
      stereochemical preferences.
AB  - AKR1C1 and AKR1C2 are human cytosolic hydroxysteroid dehydrogenases, which play
      pivotal roles in the metabolism and action of natural and synthetic steroid
      hormones. The two enzymes are highly homologous, and have distinct positional and
      stereochemical preferences with various substrates. We performed molecular
      docking simulations of three steroid substrates, including an androgen (5alpha
      dihydrotestosterone, DHT), a progestin (progesterone, PRO), and a synthetic
      hormone ([7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one or
      tibolone, TIB), into the active sites of the two enzymes. For each substrate and
      enzyme pair, the activity inferred by the "productive" docking models (in which
      the spatial arrangement of the steroid and the cofactor would permit a reaction)
      matched the experimentally observed positional and stereochemical outcome. These
      productive conformations were energetically and statistically favored except for
      TIB and PRO with AKR1C2, where experimentally strong substrate inhibition and low
      activity were observed, respectively. Results showed that (i) a 3-ketosteroid
      (DHT) and a 20-ketosteroid (PRO) were reduced by AKR1C1 since the carbonyl groups
      could occupy the same position by "backwards" binding of steroids; (ii) 3alpha
      reduced (DHT) and 3beta-reduced (TIB) products were formed by AKR1C2 since the
      angular methyl groups of the steroids were inverted by "upside-down" binding of
      steroids; and (iii) the 3beta- and 3alpha-reduction of DHT by AKR1C1 and AKR1C2,
      respectively occurred since the steroids employed a "swinging" motion to present
      opposite faces to the cofactor. Favorable nonproductive modes were observed with
      all substrates in both enzymes in which the steroid was bound at a "near-entry"
      position and/or an "in-middle" position, which may influence the reaction
      coordinate.

PMID- 16455124
TI  - Species differences among various rodents in the conversion of 7alpha
      hydroxycholesterol in liver microsomes.
AB  - Our previous study demonstrated that there are species differences among
      vertebrates in their conversion of 7alpha-hydroxycholesterol (7HC) to 7
      ketocholesterol (7KC). To examine this further, we investigated the differences
      in the products of 7alpha-hydroxycholesterol in various species of male muroid
      rodents. Adult male Syrian hamsters (Mesocricetus auratus), dwarf hamsters
      (Phodopus rovolovskii), Djungarian hamsters (Phodopus sungorus), Chinese hamsters
      (Cricetulus griseus), rat-like hamsters (Tscherskia triton), and hispid cotton
      rats (Sigmodon hispidus) were used. Microsomal fractions were prepared from their
      livers, and the activities of the enzymes that participate in the dehydrogenation
      of 7alpha-hydroxycholesterol were determined by measuring the products using high
      performance liquid chromatography. 7alpha-hydroxycholesterol was converted to
      both 7alpha-hydroxy-4-cholesten-3-one (7HCO) and 7-ketocholesterol in all of the
      hamsters tested. However, in the rat-like hamster and the hispid cotton rat,
      7alpha-hydroxycholesterol was converted mostly to 7alpha-hydroxy-4-cholesten-3
      one, as also observed in the rat (Rattus norvegicus). The results suggest that
      microsomal enzyme activity in the conversion of 7alpha-hydroxycholesterol to 7
      ketocholesterol varies considerably, even within the subfamily Cricetinae and the
      family Muridae.

PMID- 16455125
TI  - An intact sequence-specific DNA-binding domain is required for human
      cytomegalovirus-mediated sequestration of p53 and may promote in vivo binding to
      the viral genome during infection.
AB  - The p53 protein is stabilized during infection of primary human fibroblasts with
      human cytomegalovirus (HCMV). However, the p53 in HCMV-infected cells is unable
      to activate its downstream targets. HCMV accomplishes this inactivation, at least
      in part, by sequestering p53 into viral replication centers within the cell's
      nucleus soon after they are established. In order to better understand the
      interplay between HCMV and p53 and the mechanism of sequestration, we constructed
      a panel of mutant p53-GFP fusion constructs for use in transfection/infection
      experiments. These mutants affected several post-translational modification sites
      and several sites within the central sequence-specific DNA-binding domain of the
      protein. Two categories of p53 sequestration were observed when the mutant
      constructs were transfected into primary fibroblasts and then infected at either
      high or low multiplicity. The first category, including all of the post
      translational modification mutants, showed sequestration comparable to a wild
      type (wt) control, while the second category, mutants affecting the DNA-binding
      core, were not specifically sequestered above control GFP levels. This suggested
      that the DNA-binding ability of the protein was required for sequestration. When
      the HCMV genome was analyzed for p53 consensus binding sites, 21 matches were
      found, which localized either to the promoters or the coding regions of viral
      proteins involved in DNA replication and processing as well as structural
      proteins. An analysis of in vivo binding to these identified sites via chromatin
      immunoprecipitation assays revealed differential binding to several of the sites
      over the course of infection.

PMID- 16455126
TI  - Genetic analyses reveal structured HIV-1 populations in serially sampled T
      lymphocytes of patients receiving HAART.
AB  - HIV-1 infection and compartmentalization in diverse leukocyte targets
      significantly contribute to viral persistence during suppressive highly active
      antiretroviral therapy (HAART). Longitudinal analyses were performed on envelope
      sequences of HIV-1 populations from plasma, CD4+ and CD8+ T lymphocytes in 14
      patients receiving HAART and 1 therapy-naive individual. Phylogenetic
      reconstructions and analysis of molecular variance revealed that HIV-1
      populations in CD4+ and CD8+ T cells remained compartmentalized over time in most
      individuals. Analyses of viral genetic variation demonstrated that, despite
      compartmentalization remaining over time, viral subpopulations tended not to
      persist and evolve but instead broke down and became reconstituted by new founder
      viruses. Due to the profound impact of HAART on viral evolution, it was difficult
      to discern whether these dynamics were ongoing during treatment or predominantly
      established prior to the commencement of therapy. The genetic structure and viral
      founder effects observed in serially sampled T lymphocyte populations supported a
      scenario of metapopulation dynamics in the tissue(s) where different leukocytes
      become infected, a factor likely to contribute to the highly variable way that
      drug resistance evolves in different individuals during HAART.

PMID- 16455127
TI  - Cell entry of hepatitis C virus.
AB  - Hepatitis C virus (HCV), an important human pathogen, is an enveloped, positive
      stranded RNA virus classified in the hepacivirus genus of the Flaviviridae
      family. Cell attachment of flaviviruses generally leads to endocytosis of bound
      virions. Systems that support HCV replication and particle formation in vitro are
      emerging only now, 16 years after the discovery of the virus. Albeit this
      limitation, the route of HCV cell entry as well as 'capture' molecules involved
      in low-affinity interactions for the initial contact of HCV with target cells and
      potential high-affinity receptor candidates that may mediate HCV trafficking and
      fusion has been described. The objective of this review is to summarize the
      contribution of different HCV model systems to our current knowledge about
      structure of the HCV GPs E1 and E2 and their roles in cell entry comprising cell
      attachment, interactions with cellular receptors, endocytosis, and fusion.

PMID- 16455128
TI  - Effect of shock and mixed nitrophenolic loadings on the performance of UASB
      reactors.
AB  - The effect of nitrophenolic shock loads on the performance of three bench-scale
      upflow anaerobic sludge blanket (UASB) reactors was studied using synthetic
      wastewater. Reactors R1, R2 and R3 were fed with 30 mg/L concentration of 2
      nitrophenol (2-NP), 4-nitrophenol (4-NP) and 2,4-dinitrophenol (2,4-DNP),
      respectively, along with methanol (COD = 2000 mg/ L), sodium nitrate (NO3(-)
      N=200mg/L), and other nutrients. The reactors were in continuous operation for
      more than 2 years before the shock loading study was performed. Five
      nitrophenolic shock loadings of 45, 60, 75, 90 and 120mg/L d were administrated
      by increasing the influent nitrophenolic concentration to 45, 60, 75, 90 and
      120mg/L, respectively, while keeping hydraulic retention time as 24h. The shocks
      were given continuously for a period of 4 days before switching back to normal
      nitrophenolic loading (30mg/Ld). The reactors were allowed to recover to normal
      performance level before administrating the next nitrophenolic shock load. The
      study showed that the nitrophenolic shock load of as high as 120 mg/L d did not
      affect the reactors performance irreversibly. After resuming the normal
      nitrophenolic loading, it took almost 3-18 days for the reactors to recover from
      the shock effect. The study was further extended to assess the maximum possible
      mixed nitrophenolic loading (2NP:4NP:2,4:DNP = 1:1:1) to which 2,4-DNP acclimated
      granular sludge containing reactor (R3) can be exposed without hampering the
      reactor (R3) performance irreversibly. The reactor was able to achieve pseudo
      steady-state at a mixed nitrophenolic loading of 180 mg/L d with more than 90%
      removal of all the three nitrophenols, but failed at a mixed nitrophenolic
      loading of 225 mg/Ld.

PMID- 16455129
TI  - Inhibition of metamorphosis in tadpoles of Xenopus laevis exposed to
      polybrominated diphenyl ethers (PBDEs).
AB  - Tadpoles of the African clawed frog, Xenopus laevis were exposed, beginning at
      stage 50, to a commercial pentabromodiphenyl ether mixture (DE-71) through the
      diet. Subsequent experiments were conducted using a single intraperitoneal
      injection at stage 58 with limited quantities of two purified brominated diphenyl
      ether (BDE) congeners, BDE47 and BDE99 and DE-71 to determine the relative
      potency of these BDE congeners within the commercial mixture. Significant
      inhibition of tail resorption, delayed metamorphosis and impacts on skin
      pigmentation were observed in Xenopus exposed to DE-71 in the diet at nominal
      doses of 1000 and 5000 microgg(-1) of food. The estimated time required for 50%
      of the tadpoles to complete metamorphosis was significantly lengthened in Xenopus
      exposed to a dietary concentration of 1 microg DE-71 per gram of food. Analysis
      of PBDEs (sum of 32 congeners) in Xenopus from the treatment with 5000 microgg(
      1) of DE-71 indicated that the frogs accumulated an average of 1030 microgg(-1)
      (wet weight) of PBDEs. In the intraperitoneal injection trials, similar
      inhibitory responses were observed in Xenopus injected with DE-71 at a nominal
      dose of 60 microg per tadpole, or injected with BDE47 at a nominal dose of 100
      microg per tadpole. No responses were observed in Xenopus injected with BDE99 at
      doses up to 100 microg per tadpole. Complete inhibition of metamorphosis was
      observed only in the highest DE-71 dietary treatment. The results of this study
      are consistent with a mechanism of action of PBDEs involving competitive
      inhibition of binding of thyroid hormones to transporter proteins, although the
      mechanism cannot be definitively determined from this study. The observed effects
      may have occurred through other mechanisms, including sublethal toxicity. The
      doses used in this study are greater than the levels of PBDEs to which anurans
      are exposed in the environment, so further studies are required to determine
      whether exposure to PBDEs at environmentally relevant concentrations can affect
      frog metamorphosis.

PMID- 16455130
TI  - Levels of PBDEs, PCDDs, PCDFs, and coplanar PCBs in edible fish from California
      coastal waters.
AB  - The levels of polychlorinated dibenzo-dioxins (PCDDs), polychlorinated dibenzo
      furans (PCDFs), coplanar polychlorinated biphenyls (coPCBs), and polybrominated
      diphenyl ethers (PBDEs) were measured in fish collected from San Francisco Bay in
      2000 and from the California coast in 2001. The samples were composites of only
      the edible portions of the fish (skin on, skin off, or whole body minus head and
      guts) of comparable size and from distinct geographical areas. Sixty-five
      composite samples were analyzed for PCDD/PCDF/coPCBs, and 43 composite samples
      were analyzed for PBDEs. For all fish of all species from all sampling areas, the
      mean concentration of the sum of BDEs 47, 99, 100, 153, and 154 was 302 ng/g
      lipid weight, with BDE 47>100>99 approximately 154>153. For all fish of all
      species from all sampling areas, the mean PCDD/PCDF International Toxic
      Equivalent (I-TEQ) was 33.1 pg/g lipid. For the three coPCBs (77, 126, 169), the
      mean I-TEQ for all fish of all species from all sampling areas was 109 pg/g
      lipid. The highest concentrations of both PCDD/PCDF/coPCBs and PBDEs were found
      in the highly populated areas of San Francisco Bay, the Los Angeles area, and San
      Diego Bay.

PMID- 16455131
TI  - The relationship between pre-treatment clinical profile and treatment outcome in
      an integrated stuttering program.
AB  - A procedure for subtyping individuals who stutter and its relationship to
      treatment outcome is explored. Twenty-five adult participants of the
      Comprehensive Stuttering Program (CSP) were classified according to: (1)
      stuttering severity and (2) severity of negative emotions and cognitions
      associated with their speech problem. Speech characteristics (percentage of
      stuttered syllables, distorted speech score, and the number of correctly produced
      syllables on a diadochokinesis task) and emotional/cognitive states (emotional
      reaction, speech satisfaction, and attitudes toward speaking) were assessed
      before and after treatment, and at a 1- and 2-year follow-up. The results showed
      that: (a) there was no relationship between stuttering severity and the severity
      of negative emotions and cognitions, (b) the severe stuttering group had the
      largest treatment gains but also the highest level of regression, and (c) at post
      treatment and both follow-up assessments the differences on measures of emotions
      between the mild and severe emotional group had disappeared, chiefly due to a
      large decrease in the latter group's negative emotions and cognitions. Our
      findings show that, based on treatment gains, specific subgroups can be
      identified, each requiring different treatment approaches. This underlines the
      necessity of developing a better understanding of how various dimensions of
      stuttering relate to treatment outcome. EDUCATIONAL OBJECTIVES: The reader will
      be able to: (1) describe why stuttering severity and negative emotions and
      cognitions that are related to stuttering should be investigated separately and
      (2) describe how treatment outcome relates to subtypes of persons who stutter.

PMID- 16455132
TI  - Teenage parenthood among child welfare clients: a Swedish national cohort study
      of prevalence and odds.
AB  - To assess prevalence and odds for teenage parenthood among former child welfare
      clients, we used national register data for all children born in Sweden 1972-1983
      (n=1,178,207), including 49,582 former child welfare clients with varying
      intervention experiences. Logistic regression models, adjusted for demographic,
      socio-economic and familial background factors, were used to estimate odds
      ratios. Among youth who received interventions in adolescence, 16-19% of the
      girls and 5-6% of the boys became teenage parents, compared to 3% for girls and
      0.7% for boys without child welfare experiences. Youths who entered child welfare
      services in their teens had four- to fivefold adjusted odds for becoming a
      teenage parent. For other child welfare clients, adjusted odds were mostly
      twofold. Youth of both sexes who receive child welfare services in adolescence
      are a high-risk group for teenage parenthood. Child welfare agencies should, as a
      minimum, provide each individual client youth with access to birth control
      counselling and contraceptives.

PMID- 16455133
TI  - Beyond parenting practices: extended kinship support and the academic adjustment
      of African-American and European-American teens.
AB  - This study examined adolescents' perceptions of parenting practices and extended
      kinship support in relation to academic adjustment for 104 African American and
      60 European American 9th and 10th graders (14 and 15 year olds). For African
      American teens, parental acceptance was associated with school values, teacher
      bonding, and work orientation. Higher levels of behavioral control and lower
      levels of psychological control were associated with a stronger work orientation.
      After accounting for the demographic variables and the three parenting practices,
      higher levels of extended kinship support related to stronger school values,
      higher teacher bonding, and a stronger work orientation. For European-American
      teens, parental acceptance related to academic adjustment, including stronger
      school values, higher teacher bonding, and a stronger work orientation. European
      American adolescents with stronger extended kinship networks reported higher
      teacher bonding and a stronger work orientation. Results indicate the importance
      of extended kinship support for both African-American and European-American
      adolescents.

PMID- 16455134
TI  - Expansion of chondroprogenitor cells on macroporous microcarriers as an
      alternative to conventional monolayer systems.
AB  - Routine tissue culture methodologies can hardly cope with the scale of cell
      production required for the manufacture of engineered cartilage tissue products.
      In vitro cell expansion has become an essential step in the process of tissue
      engineering of articular cartilage and the optimization of expansion protocols is
      a fundamental issue that needs to be addressed. The expansion suitability of
      chondroprogenitor cells isolated from the superficial zone of articular
      cartilages was evaluated in both conventional monolayer and macroporous
      microcarrier in spinner flask cultures. Although monolayer systems promoted rapid
      in vitro expansion of undifferentiated cells, they present limited scalability.
      Alternatively, the use of CultiSpher-G microcarriers resulted in cell densities
      of 5.5 x 10(5) cell/ml, representing a 17-fold expansion in batch cultures. In
      addition, chondroprogenitor cells were capable of undergoing bead-to-bead
      migration, which allowed subcultivation to be performed without a harvesting
      step, thus improving the scalability of the expansion process. By employing
      macroporous microcarrier cultures it will be possible to obtain large number of
      chondroprogenitor cells for tissue engineering applications. Not only its
      satisfactory expansion potential, but more importantly the cost and operational
      advantages over traditional monolayer culture make this system a feasible
      alternative method for the extensive expansion of chondroprogenitor cells.

PMID- 16455135
TI  - Maskless liquid-crystal-display projection photolithography for improved design
      flexibility of cellular micropatterns.
AB  - We previously developed an all-in-one photopolymerization device by modifying a
      commercially available liquid crystal display projector (LCDP) for the
      preparation of micropatterned surfaces and microfluidic channels without the need
      for expensive photomasks. In the present study, we demonstrate a simple and
      reliable method for rapid prototyping of cell micropatterning with high
      resolution using the modified LCDP device. Fabrication of complicated and
      flexible patterns was achieved using this device with positive-type photoresist
      in a two-step process. First, micropatterns on the silanized coverslips were
      fabricated from positive photoresist. Second, acrylamide monomer solution
      containing polymerization initiator was dropped onto the micropatterned positive
      photoresist and copolymerized on the silanized coverslips in situ by thermally
      initiated radical polymerization. After the reaction, the remnant micropatterned
      photoresist is easily dissolved, resulting in a polyacrylamide-silane
      micropattern on the coverslip. The resultant polyacrylamide layer is highly
      hydrophilic and repels both protein adsorption and cell adhesion. Cells seeded on
      the micropatterned surfaces therefore attach and spread only on unpolymerized
      silanized glass surfaces, conforming to the pattern design. This technique is
      therefore useful for inexpensive, rapid prototyping of surface micropatterns
      using polymer materials.

PMID- 16455136
TI  - Towards developing surface eroding poly(alpha-hydroxy acids).
AB  - We have prepared a library of biodegradable polyesters derived from poly(alpha
      hydroxy acids) (PHAs) that appear to primarily exhibit surface erosion behavior.
      This was achieved by increasing the hydrophobicity of the polymers in two
      distinct steps, namely: macromer formation and a coupling step. In the first
      step, macromerdiols (MDs) with varying lipophilicities were prepared by
      polymerization of L-lactide or mixture of L-lactide and glycolide (3/1 by mole)
      to various lengths (n = 10, 20, 30, and 40) using alkanediols of increasing C
      chain length (C6, C8, and C12) as initiators in the presence of Tin(II) catalyst.
      In the second step, the macromer diols were linked together with diacid
      dichlorides of varying C-chain lengths (C6, C8, C10, and C12) to yield polyesters
      ranging in molecular weight (Mw) from 20 to 130 KDa and polydispersity of 1.5-6.
      These polyesters exhibited different thermal behavior from pure PHAs that can be
      tuned by changing the initiator core, the lactide/glycolide chain length, and
      diacid dichloride type. In addition, all these polymers showed solubility in
      tetrahydrofuran unlike poly(L-lactic acid) (PLLA) and poly(lactide-co-glycolide)
      (PLGA). In contrast to PLLA and PLGA, the degradation behavior of these novel
      polyesters exhibited linear profiles consistent with a surface erosion behavior.
      Release studies using Congo red as a model drug from microspheres prepared from
      these polyesters showed linear release profiles with correlation constants of
      least-square fits approaching a value of unity. Degradable polyesters with
      tunable thermal and degradation behavior may find applications in drug delivery
      and tissue engineering, where control over these parameters is critical to ensure
      predictable outcomes.

PMID- 16455137
TI  - In search of the sea monster.
AB  - The sea monster played an important part in launching the Danish Galathea Deep
      Sea Expedition of 1950-1952. Part scientific object, part media darling and part
      fundraising strategy, the sea monster brought scientists, journalists and
      politicians together in support of the expedition. The scientific leader of the
      expedition, Anton F. Bruun, contended the scientific reality of such a creature;
      the leader of the press section attached to the expedition, Hakon Mielche, dreamt
      of the grand headlines finding the sea monster would attract; and everyone
      involved used the 'poor little thing' to promote the expedition to sponsors and
      in public.

PMID- 16455138
TI  - Highly phagocytic, CD4hi, CD14hi and CD16hi antigen-presenting cells modulated by
      tumour-conditioned media retain the capacity to mature and induce TH1 T-cell
      proliferation.
AB  - The tumour microenvironment down-modulates antigen-presentation by dendritic
      cells (DC), presumably due to inhibition of DC maturation. Here, we sought to
      examine (1) whether monocyte-derived cells cultivated with tumour-conditioned
      media under conditions that are conducive to DC generation (APCTCM) resemble
      immature DC (iDC), IL-10-induced regulatory DC (DCIL10) or display other
      distinctive features; (2) whether APCTCM are convertible to immunostimulatory DC
      (DCims) upon proper activation and (3) whether APCTCM and activated APCTCM are
      functionally defective. Four tumour cell lines expressing different cytokines
      were used to mimic different tumour microenvironments. As compared to iDC, DCims
      or DCIL10, APCTCM exhibited the highest levels of expression for CD14, CD16 and
      CD4. These markers and a high phagocytic capacity were unique features of these
      cells. When APCTCM were activated by a maturation cocktail, CD83, CD86, HLA-DR
      and CD25 were up-regulated to levels considerably higher than in DCIL10 and
      comparable to DCims while CD14, CD16, CD4 and dextran-uptake were down-modulated.
      Activated APCTCM induced 50-60% of the proliferative response of DCims in the
      allogeneic T-cell proliferation assay while DCIL10 mounted a 20-30% response (iDC
      elicited approximately 10%). Activated APCTCM induced secretion of almost equal
      amounts of IFN-gamma, TNF-alpha and IL-2 as DCims indicating induction of Th1
      differentiation. When mature DCims were exposed to TCM, their immunostimulatory
      function was not significantly altered. However, when TCM were added to the co
      cultures of DCims and CD4 T-cells the proliferative outcome was dependent on the
      TCM. In summary, APCTCM display special features but can mature into DCims-like
      cells.

PMID- 16455139
TI  - Effects of developmental co-exposure to methylmercury and 2,2',4,4',5,5'
      hexachlorobiphenyl (PCB153) on cholinergic muscarinic receptors in rat brain.
AB  - The developing nervous system is thought to be particularly sensitive to
      polychlorinated biphenyls (PCBs) present as food contaminants together with
      methylmercury (MeHg). Effects of perinatal co-exposure to PCB153 and MeHg on
      brain cholinergic muscarinic receptors (MRs) were investigated by saturation
      binding studies in mature and immature rats. MeHg alone (1mg/kg/day, GD7-PND7)
      enhanced cerebral MRs more in dams (87% and 60% in cerebellum and cerebral
      cortex, respectively) than in PND21 pups (0-50%) in accordance with the higher Hg
      levels detected in the adult brain (7-9 microg/g) than in the male and female
      offspring's brain (1.5-2.8 microg/g). Prenatal administration of PCB153
      (20mg/kg/day, GD10-GD16), leading to higher contaminant levels in the offspring
      brain than in that of adults (25-66 microg/g versus 3 microg/g), induced cerebral
      MR changes of similar extent at both ages, namely decreased cerebellar (20-30%)
      and increased cortical MR density (40-50%). Co-exposure to PCB and MeHg had no
      more effect than exposure to either compound alone on cerebral cortex MRs,
      whereas, in the cerebellum, the combined treatment induced a PCB-like lowering of
      the MR density that masked the MeHg-induced receptor increase. None of the
      treatments affected the striatal and hippocampal MRs. A lower MeHg dose (0.5
      mg/kg/day) was without any effect on cerebral MRs. These results show that MRs
      are one of the sensitive biochemical endpoints of the central nervous system
      altered by developmental exposure to MeHg and PCB153. Cerebral cortex and
      cerebellum were the most susceptible targets in the response to these
      neurotoxicants. MR changes were detected in both immature and adult animals and
      the interaction of MeHg and PCB153 at the level of these receptors occurred in a
      non-additive manner.

PMID- 16455140
TI  - A study of the coordination shell of aluminum(III) and magnesium(II) in model
      protein environments: thermodynamics of the complex formation and metal exchange
      reactions.
AB  - Al(III) toxicity in living organisms is based on competition with other metal
      cations. Mg(II) is one of the most affected cations, since the size similarity
      dominates over the charge identity. The slow ligand exchange rates for Al(III)
      render the ion useless as a metal ion at the active sites of enzymes and provide
      a mechanism by which Al(III) inhibits Mg(II) dependent biochemical processes.
      Al(III) cation interactions with relevant bioligands have been studied in a
      protein-model environment in gas and aqueous phases using density functional
      theory methods. The protein model consists of the metal cation bound to two
      chosen bioligands (functional groups of the amino acid side chains, one of them
      being always an acetate) and water molecules interacting with the cation to
      complete its first coordination shell. Analogous Mg(II) complexes are calculated
      and compared with the Al(III) ones. Formation energies of the complexes are
      calculated in both phases and magnesium/aluminum exchange energies evaluated. The
      effect of different dielectric media is also analyzed. The presence of an acetate
      ligand in the binding site is found to promote both, complex formation and metal
      exchange reactions. In addition, buried binding sites (with low dielectric
      constant) of the protein favor metal exchange, whereas fully solvated
      environments of high dielectric constant require the presence of two anionic
      ligands for metal exchange to occur.

PMID- 16455141
TI  - Role of lipids in the MAPK signaling pathway.
AB  - The mitogen-activated protein kinase (MAPK) signaling pathway is activated in
      response to a variety of extracellular stimuli such as growth factor stimulation.
      The best-characterized MAPK pathway involves the sequential activation of Raf,
      MEK and ERK proteins, capable of regulating the gene expression required for cell
      proliferation. Binding to specific lipids can regulate both the subcellular
      localization of these MAPK signaling proteins as well as their kinase activities.
      More recently it has become increasingly clear that the majority of MAPK
      signaling takes place intracellularly on endosomes and that the perturbation of
      endocytic pathways has dramatic effects on the MAPK pathway. This review
      highlights the direct effects of lipids on the localization and regulation of
      MAPK pathway proteins. In addition, the indirect effects lipids have on MAPK
      signaling via their regulation of endocytosis and the biophysical properties of
      different membrane lipids as a result of growth factor stimulation are discussed.
      The ability of a protein to bind to both lipids and proteins at the same time may
      act like a "ZIP code" to target that protein to a highly specific microlocation
      and could also allow a protein to be "handed off" to maintain tight control over
      its binding partners and location.

PMID- 16455142
TI  - Identity state-dependent attentional bias for facial threat in dissociative
      identity disorder.
AB  - Biased attention for threatening stimuli has been associated with many forms of
      psychopathology. Attention to threatening faces presented below perceptual
      thresholds was assessed in patients diagnosed with dissociative identity disorder
      using a pictorial emotional Stroop task. Patients were tested in two different
      identity states, in one of which they claimed strong awareness of trauma.
      Attentional bias for social threat proved state-dependent in the patients and
      deviated from the patterns observed in controls.

PMID- 16455143
TI  - The protective immune response induced by B cell epitope of classical swine fever
      virus glycoprotein E2.
AB  - Classical swine fever virus (CSFV) envelope glycoprotein E2 is a major protective
      immunogen responsible for eliciting neutralizing antibodies and conferring
      protective immunity against the virus. Based on the core sequence (TAVSPTTLR, 829
      837 aa) of the B cell linear epitope of the CSFV E2 protein identified by Lin et
      al., two oligonucleotides MF and MR were synthesized and used to construct by PCR
      a gene cassette encoding a 15 amino acid polypeptide M (CTAVSPTTLRTEVVK), which
      spans 828-842 amino acids of E2. The gene cassette was fused in-frame to 3'
      terminal of glutathione S transferase gene (GST) of the prokaryotic expression
      vector pGEX-6p-1, resulting in the recombinant plasmid pGEX-M. After
      transformation into Escherichia coli BL21 a soluble fusion protein GST-M with
      expected size of 28 kDa was expressed after inducing with isopropyl-beta-d
      thiogalactoside (IPTG). Enzyme-linked immunosorbent assay (ELISA) and Western
      blot analysis showed that the purified GST-M had good reactivity with swine anti
      CSFV serum and rabbit anti-CSFV E2 serum. Further vaccination trials showed that
      the fusion protein GST-M could elicit effectively immune response protecting
      rabbits and pigs from virulent challenge. This study showed a possibility for
      developing epitope-based vaccines against CSFV.

PMID- 16455144
TI  - The role of the dorsal CA3 hippocampal subregion in spatial working memory and
      pattern separation.
AB  - A delayed-match-to-sample for spatial location task was used to measure spatial
      pattern separation and working memory. On each trial, an object covered a baited
      food well in one of 15 spatial locations along a row of food wells perpendicular
      to the start box. Once the rat exited the start box, displaced the object to
      receive a food reward and then returned to the startbox, the same food well was
      then quickly re-baited, an identical object was positioned to cover the food well
      and another identical object was positioned in a different location along the row
      of food wells covering a different unbaited food well. On the ensuing choice
      phase, the animal was allowed to choose between the two objects. The object that
      covered the same food well as the object in the sample phase was the correct
      choice and the second foil object was the incorrect choice. Five spatial
      separations (15-105 cm) were randomly used to separate the correct object from
      the foil object during the choice phase. Once a preoperative criterion was met,
      each rat received bilateral intracranial infusions of either ibotenic acid or the
      vehicle into the CA3 subregion of the dorsal hippocampus. Following surgery, rats
      with CA3 lesions were significantly impaired relative to controls across all
      spatial separations suggesting that CA3 lesions impaired working memory. Although
      the dorsal CA3 subregion of the hippocampus may play a role in pattern
      separation, the data suggest that this region is critically involved in spatial
      working memory.

PMID- 16455145
TI  - Social isolation selectively reduces hippocampal brain-derived neurotrophic
      factor without altering plasma corticosterone.
AB  - It is well known that housing conditions may alter several physiological and
      behavioral parameters. In this study, we have investigated whether a prolonged
      period of partial social isolation can modify central brain-derived neurotrophic
      (BDNF) concentrations. Male Sprague-Dawley rats were singly housed for 8 weeks
      before hippocampi, prefrontal cortices and striata were collected for BDNF
      determination. Compared to rats housed two per cage, isolated rats showed a
      significant reduction on BDNF protein concentrations in the hippocampus while no
      changes were observed in the other brain regions examined. Moreover, housing
      condition had no effect on basal plasma corticosterone. On the basis of the
      proposed etiological participation of reduced central BDNF concentrations in
      affective disorders, our results would candidate social isolation as a model for
      the study of antidepressant treatments.

PMID- 16455146
TI  - Differential oxidative stress responses to microcystins LR and RR in
      intraperitoneally exposed tilapia fish (Oreochromis sp.).
AB  - Increasing evidence suggests that oxidative stress may play a significant role in
      causing microcystin (MCs) toxicity not only in mammals, but also in fish. MCs are
      a family of cyclic peptide toxins produced by some species of freshwater
      cyanobacteria (blue-green algae). Among the microcystins, MC-LR is the most
      extensively studied. In the present study the differential response of the
      antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx) and glutathione reductase (GR) as well as lipid peroxidation
      (LPO) as a biomarker of oxygen-mediated toxicity were assessed in liver, kidney
      and gill tissues of tilapia (Oreochromis sp.) exposed to MCs. Fish were injected
      intraperitoneally (i.p.) with a single dose of 500 microg/kg MC-LR or 500
      microg/kg MC-RR and sacrificed after 7 days. The results show that MCs exposure
      induces adaptive responses such as increase in the antioxidant enzymatic
      activities, mainly those of SOD and CAT, as well as in LPO values. With regard to
      LPO values, the liver was the most affected organ by MC-LR. MC-RR, however, did
      not affect this parameter in the liver of the exposed fish. Oxidative stress
      biomarkers, therefore, are valuable tools in the assessment of early responses of
      fish to the increasing occurrence of cyanobacterial blooms worldwide.

PMID- 16455147
TI  - Transvenous radiofrequency catheter ablation of atrioventricular nodal reentrant
      tachycardia and its pitfalls: a rationale for cryoablation?
AB  - Today, radiofrequency (RF) catheter ablation of atrioventricular nodal reentrant
      tachycardia (AVNRT) is accompanied by a high success, a low recurrence, and a low
      complication rate. Despite the fact that over the years this technique has been
      refined, several shortcomings still remain. In this overview, the most important
      pitfalls in the treatment of AVNRT with RF energy are discussed. Cryotherapy has
      the ability to overcome some of them. Both ice mapping and cryo-adherence are
      important characteristics of this energy source to study prospective ablation
      sites before a definitive and irreversible lesion is created. Theoretically, this
      could lead to less applications with less tissue damage and abolish the risk for
      permanent conduction disturbances. The early experience with this technique will
      be described. Until now, it still has to be proven that in a large cohort of
      patients, cryotherapy is at least as effective, and safer than RF.

PMID- 16455148
TI  - Tirapazamine causes vascular dysfunction in HCT-116 tumour xenografts.
AB  - BACKGROUND AND PURPOSE: Tirapazamine is a hypoxic cytotoxin currently undergoing
      Phase II/III clinical evaluation in combination with radiation and
      chemotherapeutics for the treatment of non-hematological cancers. Tissue
      penetration studies using multicellular models have suggested that tirapazamine
      exposure may be limited to cells close to blood vessels. However, animal studies
      show tirapazamine enhances the anti-tumour activity of radiation and chemotherapy
      and clinical studies with tirapazamine, so far, are promising. To investigate
      this apparent paradox we examined the microregional effects of tirapazamine in
      vivo by mapping drug effects with respect to the position of blood vessels in
      tumour cryosections. PATIENTS AND METHODS: Tirapazamine was administered i.p. to
      mice bearing HCT-116 tumours, which were excised at various times after
      treatment. Images of multiple-stained cryosections were overlaid to provide
      microregional information on the relative position of proliferating cells,
      hypoxia, perfusion and vasculature. RESULTS: We observed extensive and permanent
      vascular dysfunction in a large proportion of tumours from mice treated with
      tirapazamine. In the affected tumours, blood flow ceased in the centrally located
      tumour vessels, leaving a rim of functional vessels around the periphery of the
      tumour. This vascular dysfunction commenced within 24 h after tirapazamine
      administration and the areas affected appeared to be replaced by necrosis over
      the following 24-48 h. CONCLUSIONS: Because the majority of hypoxic cells are
      located in the center of tumours we propose that the activity of tirapazamine in
      vivo may be related to its effects on tumour vasculature and that its activity
      against hypoxic cells located distal to functional blood vessels may not be as
      important as previously believed.

PMID- 16455149
TI  - Dual release of proteins from porous polymeric scaffolds.
AB  - To create porous scaffolds releasing in a controlled and independent fashion two
      different proteins, a novel approach based on protein-loaded polymeric coatings
      was evaluated. In this process, two water-in-oil emulsions are forced
      successively through a prefabricated scaffold to create coatings, containing each
      a different protein and having different release characteristics. In a first
      step, a simplified three-layered system was designed with model proteins
      (myoglobin and lysozyme). Poly(ether-ester) multiblock copolymers were chosen as
      polymer matrix, to allow the diffusion of proteins through the coatings. The
      model system showed the independent release of the two proteins. The myoglobin
      release was tailored from a burst to a linear release still on-going after 60
      days, while the lysozyme release rate was kept constant. Macro-porous scaffolds,
      with a porosity of 59 vol.%, showed the same ability to control the release rate
      of the model proteins independently. The relation between the coatings properties
      and their release characteristics were investigated with the use of a
      mathematical diffusion model based on Fick's second law. It confirmed that the
      multiple coated scaffolds are biphasic system, where each coating controls the
      release of the protein that it contains. This approach could be of value for
      tissue engineering applications.

PMID- 16455150
TI  - A distinctive fatty acid profile in circulating lipids of Korean gestational
      diabetics: a pilot study.
AB  - Gestational diabetes mellitus (GDM) is a transient metabolic disorder that is a
      strong predictor of type 2 diabetes and cardiovascular disease. Previously, GDM
      was associated with reduced red cell long-chain omega-6 and omega-3 fatty acids
      in population (British) with high intake of total and saturated fat. The aim of
      the study was to examine blood fatty acids status of GDM patients (n=12) and
      normoglycaemic women (control, n=12) from South Korea where typical diet retains
      high omega-3 fat with low total fat intake. Subjects were matched for BMI and
      gestation week. Blood obtained at delivery were analyzed for plasma
      triacylglycerols (TG), phosphatidylcholine (PC), sphingomyelin (SM), and red cell
      PC, phosphatidylethanolamine (PE) and SM fatty acids. GDM patients had lower
      total saturated fatty acids (SFA) in the plasma TG (p<0.05) and PC (p<0.0001),
      and higher omega-6 and omega-3 metabolites in the plasma PC (p<0.05) than the
      controls. Conversely, the red cell PC and PE of the GDM contained higher
      proportions of palmitic (p<0.05) and SFA (p<0.05) but lower arachidonic (p<0.05)
      and docosahexaenoic (p>0.05) acids compared with the controls. Interestingly, red
      cell PC arachidonic acid level was comparable between Korean and British women
      whereas docosahexaenoic acid level decreased in the order of Korean control
      (5.5+/-0.9)>Korean GDM (3.5+/-2.1)=British control (3.9+/-2.9)>British GDM (2.8+/
      2.3) (p<0.05). The similarity in the plasma and red cell fatty acids profile
      between Korean and British cohort suggests that the reduced membrane arachidonic
      and docosahexaenoic acids in GDM might be attributed to the effect of the disease
      itself regardless of ethnicity, obesity, or diet.

PMID- 16455151
TI  - HBV drug resistance: mechanisms, detection and interpretation.

PMID- 16455152
TI  - Efficiency differences in computational simulations of the total cavo-pulmonary
      circulation with and without compliant vessel walls.
AB  - The Fontan operation is a palliative surgical procedure performed on children
      born with congenital defects of the heart that have yielded only a single
      functioning ventricle. The total cavo-pulmonary connection (TCPC) is the most
      popular variant of the Fontan procedure. The objective of the study was to
      quantify and compare the efficiency of numerical models of the TCPC with rigid
      versus elastic vessel wall models. The pressure drop and power loss through both
      type TCPC models was measured. Significant differences in efficiencies exist
      between rigid versus elastic numerical models. We have shown incorporating
      elasticity into numerical models of the total cavo-pulmonary connection is
      important when determining circuit efficiencies.

PMID- 16455153
TI  - Quantitative imaging of contaminant distributions in heterogeneous porous media
      laboratory experiments.
AB  - Intermediate-scale laboratory experiments on heterogeneous porous media have been
      increasingly used for the study of saturated and unsaturated ground water
      systems. While the ability to reproduce field-scale heterogeneity in these
      experiments has advanced, the use of visualization or image analysis methods to
      characterize the spatial distribution of solute concentrations has largely
      remained at the homogeneous media level. To advance these imaging techniques we
      developed a generic image analysis package that, for the first time,
      automatically segments regions in photographic images that require unique
      concentration calibration curves due to varying porous media properties or
      lighting nonuniformities. As a robust test, our image analysis package was
      applied to an intermediate-scale flow tank experiment characterized by a
      correlated random permeability field with unprecedented resolution. Twenty-five
      distinct classes of porous media were developed and binned to the synthetic
      permeability field, creating an experimental field of 3456 rectangular cells and
      thereby ensuring the emplaced field closely matched the statistics of the
      original continuous distribution. Concentration distributions were determined for
      an experimental tracer run and the corresponding dispersion parameters were
      calculated. The closeness of the experimental, image-processed longitudinal
      dispersivity (4.6 x 10(-2) m) to that obtained from the field statistics (9.1 x
      10(-2) m) verifies our image analysis technique.

PMID- 16455154
TI  - Champion students! Experience with a standardized infection control training
      package in medical students.

PMID- 16455155
TI  - Knowledge of nosocomial infections and multiresistant bacteria in the general
      population: results of a street interview.

PMID- 16455156
TI  - Safe disposal of infectious waste--Indian perspective.

PMID- 16455158
TI  - Glove use by ancillary and support staff: a paradox of prevention?

PMID- 16455157
TI  - Lowering standards of clinical waste management: do the hazardous waste
      regulations conflict with the CDC's universal/standard precautions?
AB  - Clinical waste is a costly and troublesome commodity. Comprising the detritus of
      medical care, the foremost hazard is the risk of infection from micro-organisms
      present in these wastes. Infection commonly occurs through penetrating injury,
      the so-called 'sharps' or 'needlestick' injury, although contamination of non
      intact skin or splashes to the eye may transmit infection. Bloodborne viruses
      (hepatitis B, hepatitis C, human immunodeficiency virus) are the most serious
      threat, although respiratory, soft tissue and enteric infections are not unknown.
      The European Hazardous Waste Directive, that harmonizes the categorization and
      control of wastes, permits downregulation of clinical wastes where the risk of
      infection may be low. Although strengthened by the requirement for risk
      assessment in waste classification, UK regulatory guidance promoting
      classification of some clinical wastes as non-hazardous completely ignores the
      Centers for Disease Control and Prevention's Universal Precautions for the
      prevention of transmission of human immunodeficiency virus, hepatitis B virus and
      other bloodborne pathogens in healthcare settings, which seek to prevent
      bloodborne virus infection in healthcare workers and others, and the more
      extensive Standard Precautions that extend these principles to the prevention of
      healthcare-associated infections and the environmental spread of nosocomial
      pathogens. By creating a potent cost driver encouraging downregulation of some
      clinical wastes, UK legislation based on the European Hazardous Waste Directive
      conflicts with the CDC's Universal/Standard Precautions.

PMID- 16455160
TI  - Increasing macrolide susceptibility of methicillin-resistant Staphylococcus
      aureus.

PMID- 16455159
TI  - Clinical and environmental distribution of Legionella pneumophila in a university
      hospital in Italy: efficacy of ultraviolet disinfection.
AB  - The molecular epidemiology of Legionella pneumophila in the 'V. Monaldi'
      University Hospital was studied. Seven cases of nosocomial Legionnaires' disease
      were diagnosed between 1999 and 2003. Two clinical legionella strains obtained
      from two patients in the adult cardiac surgery unit (CSU) and 30 environmental
      legionella strains from the paediatric and adult CSUs, neonatal intensive care
      unit (NICU) and the cardiorespiratory intensive care unit (CR-ICU) were serotyped
      and genotyped. L. pneumophila serogroup 1/Philadelphia with an identical pulsed
      field gel electrophoresis (PFGE) profile A was isolated from two patients in the
      adult CSU, and from three and one water samples taken in the adult CSU and the
      paediatric CSU, respectively, from 2001 to 2002. Furthermore, L. pneumophila
      serogroup 3 with an identical PFGE profile B was identified in 20 environmental
      strains from all wards, L. pneumophila serogroup 3 with PFGE profile C was
      identified in a single environmental strain from the CR-ICU, and non-pneumophila
      Legionella with identical PFGE profile D was identified in five environmental
      strains from the adult CSU, paediatric CSU and NICU. Ultraviolet irradiation was
      effective in disinfection of the hospital water supplies in the adult and
      paediatric CSUs contaminated by L. pneumophila clone associated with nosocomial
      Legionnaires' disease. In conclusion, these data demonstrate that two cases of
      nosocomial legionellosis were caused by the persistence of a single clone of L.
      pneumophila serogroup 1/Philadelphia in the hospital environment, and that
      disinfection by ultraviolet irradiation may represent an effective measure to
      prevent nosocomial Legionnaires' disease.

PMID- 16455161
TI  - Mortality and gram-negative rod bacteraemia in the intensive care unit.
AB  - This study identified 37 intensive care unit (ICU) patients with gram-negative
      rod (GNR) bacteraemia. The sources, causative organisms and mortality of gram
      negative bacteraemia were consistent with historical series. Antibiotic
      resistance among well-described species with a propensity for antimicrobial
      resistance was the most common reason for ineffective antibiotic administration.
      This study emphasizes the importance of antibiotic resistance in antimicrobial
      selection and the power of Acute Physiology and Chronic Health Evaluation
      criteria for predicting patient mortality.

PMID- 16455163
TI  - Risk control of surgical site infection after cardiothoracic surgery.
AB  - The purpose of this prospective study was to investigate whether a risk control
      programme based on risk assessment, new treatment modalities and the presence of
      a surveillance programme reduces the incidence of surgical site infections (SSI).
      Between January 2001 and December 2003, 167 patients were treated for a total of
      183 SSIs. Data were collected on pre-operative risk factors, intra-operative data
      and postoperative recovery, including complications, infecting organisms, SSI
      treatment techniques and length of hospital stay. In this series, the total
      incidence of SSI was 5.6%. The mean age of affected patients was 65.1 years with
      a range of 20-87 years. Mean intensive care and hospital stay for SSI was 3.6
      days and 18.8 days, respectively. Total mortality was 4.8%. Many risk factors
      were encountered, some of which were associated with a high morbidity. The
      majority of SSIs were treated by topical negative pressure therapy (N=81), which
      gave few side-effects and good clinical results. After starting the surveillance
      programme, a steady decline in prevalence was observed from 8.9% to 3.9%. This
      series adds to the evidence that SSI after cardiothoracic surgery is a major but
      mainly preventable cause of morbidity and mortality. Risk factor assessment,
      application of novel treatment modalities and an adequate surveillance system all
      increased patient safety.

PMID- 16455162
TI  - Community-onset healthcare-associated MRSA bacteraemia in a district general
      hospital.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with
      significant mortality and morbidity. This retrospective study involved 76
      episodes over four years in a district general hospital in the UK. Twenty-eight
      of these episodes (36.8%) occurred within 72 h of admission. All of these,
      however, had risk factors for MRSA acquisition and were classified as healthcare
      associated bacteraemias. The mortality rates (all causes) at seven days and three
      months were 31.5% and 53.4%, respectively. Ten patients died before targeted
      therapy could be commenced. All patients in the study had multiple comorbidities,
      and pneumonia was a common diagnosis. Previous antibiotics, increased age,
      admission on surgical wards/intensive care units, and the presence of central
      venous cannulae and urinary catheters were risk factors for infection. In 48.7%
      of episodes, patients were not known to be colonized with MRSA prior to their
      bacteraemia. Empirical targeted therapy should be given to patients with risk
      factors for MRSA and staphylococci in blood cultures pending susceptibility
      results. Increased use of screening may also be required to reduce transmission
      and increase the likelihood of appropriate empirical antimicrobial therapy.
      Eradication of MRSA from carriers in the community should be considered to reduce
      the number of community-onset healthcare-associated bacteraemias.

PMID- 16455164
TI  - You say lipofuscin, we say ceroid: defining autofluorescent storage material.
AB  - Accumulation of intracellular autofluorescent material or "aging pigment" has
      been characterized as a normal aging event. Certain diseases also exhibit a
      similar accumulation of intracellular autofluorescent material. However,
      autofluorescent storage material associated with aging and disease has distinct
      characteristics. Lipofuscin is a common term for aging pigments, whereas ceroid
      is used to describe pathologically derived storage material, for example, in the
      neuronal ceroid lipofuscinoses (NCLs). NCLs are a family of neurodegenerative
      diseases that are characterized by an accumulation of autofluorescent storage
      material (ceroid) in the lysosome, which has been termed "lipofuscin-like". There
      have been many studies that describe this autofluorescent storage material, but
      what is it? Is this accumulation lipofuscin or ceroid? In this review we will try
      to answer the following questions: (1) What is lipofuscin and ceroid? (2) What
      contributes to the accumulation of this storage material in one or the other? (3)
      Does this material have an effect on cellular function? Studying parallels
      between the accumulation of lipofuscin and ceroid may provide insight into the
      biological relevance of these phenomena.

PMID- 16455165
TI  - Intranasal immunization with human papillomavirus type 16 capsomeres in the
      presence of non-toxic cholera toxin-based adjuvants elicits increased vaginal
      immunoglobulin levels.
AB  - Prophylactic immunization against human papillomaviruses (HPVs) aims
      preferentially at the generation of antibodies, which are directed against the
      virus capsid proteins. DNA-free virus-like particles or their pentameric
      subunits, the capsomeres represent suitable antigens. Here we investigated if
      anti-HPV16 L1 specific antibodies and L1-specific CTL induced by intranasal
      immunization with capsomeres in sera and vaginal washings of C57Bl6 mice can be
      enhanced by co-application of the non-toxic cholera toxin adjuvants CTA1-D2D1 or
      CTB. We found that CTA1-D2D1 elevated L1-specific serum IgG antibodies in a dose
      dependent manner and both CTA1-D2D1 and CTB significantly increased L1-specific
      IgA antibody levels in the vaginal lumen. Furthermore, CTA1-D2D1 and CTB enhanced
      L1-specific CTL responses.

PMID- 16455166
TI  - Optimal organization of a polypeptide-based candidate cancer vaccine composed of
      cryptic tumor peptides with enhanced immunogenicity.
AB  - Polyspecific tumor vaccination should offer broad control of tumor cells and
      reduce the risk of emergence of immune escape variants. Here, we evaluated the
      capacity of a polypeptide composed of optimized cryptic peptides derived from
      three different universal tumor antigens (TERT988Y, HER-2/neu402Y and MAGE
      A248V9) to induce a polyspecific CD8 cell response both in vivo in HHD mice and
      in vitro in humans. A mixture of TERT988Y, HER-2/neu402Y and MAGE-A248V9 peptides
      failed to induce a trispecific response. In contrast, a polypeptide composed of
      the three peptides stimulated a trispecific immune response. Interestingly, the
      capacity of the polypeptide to induce a trispecific response depended on its
      internal organization. Six different polypeptide variants corresponding to all
      possible combinations of the three peptides were tested. Only one variant, named
      Poly-6, elicited an immune response simultaneously targeting all three peptides.

PMID- 16455167
TI  - Determining indications for adult vaccination: patient self-assessment, medical
      record, or both?
AB  - CONTEXT: Eight or more vaccines may be indicated for adults in the United States.
      Determining if any vaccines are needed requires integrating information on the
      patient's demographic and behavioral risk factors and health status, the health
      status of the patient's close contacts, and the patient's immunization history.
      This process can be time consuming for providers and their staff. We used patient
      self-assessment as a method of determining which vaccines are indicated for a
      patient and whether indicated vaccines had been received. DESIGN, SETTING, AND
      PARTICIPANTS: Cross-sectional convenience sample of 300 adults in three family
      practice settings. Participants completed a self-assessment tool to determine if
      influenza, pneumococcal, measles, mumps, and rubella (MMR), tetanus, hepatitis A
      and hepatitis B vaccines were indicated and previously received. A chart audit
      was then performed to obtain similar information. MAIN OUTCOME MEASURES:
      Agreement (kappa statistic [< 0.00: poor agreement; 0.00-0.20: slight; 0.21-0.40:
      fair; 0.41-0.60: moderate; 0.61-0.80: substantial; 0.81-1.00: almost perfect])
      between the self-assessment tool and the audit for (1) indicated vaccines and (2)
      previous receipt of indicated vaccines indicated according to both the assessment
      form and the audit. RESULTS: Agreement between the self-assessment tool and chart
      review was substantial or better only for pneumococcal and MMR vaccines
      (kappa=0.65 and 0.85, respectively). For influenza vaccine, agreement improved
      (from kappa = 0.56 to kappa = 0.74) when indications attributable to health
      conditions of family members were excluded. Agreement regarding receipt of
      vaccines was highest for influenza vaccine (kappa = 0.70). Only 57% of patients
      correctly recalled tetanus vaccination that were documented in the medical record
      (kappa = -0.04). Kappa statistics were unreliable for hepatitis A and B vaccines
      because so few vaccinations had been received. CONCLUSIONS: Discrepancies in
      agreement regarding indications for vaccines appeared to result from absence of
      information in the medical record regarding high risk behaviors and family
      contacts. Lack of agreement regarding vaccines that had been previously been
      received appeared due to both poor recall and lack of documentation. Combining
      medical record audit with self-assessment may be the most complete assessment of
      vaccination status of adults, but requires reconciling disagreements. Electronic
      medical records and registries that contain information about risk factors and
      previously administered vaccines may be necessary to overcome some these
      problems.

PMID- 16455168
TI  - Intranasal immunization of Balb/c mice against prion protein attenuates orally
      acquired transmissible spongiform encephalopathy.
AB  - To test whether prion protein (PrP) specific secretory immunoglobulin A (sIgA)
      can be induced and protect against oral transmission of spongiform encephalopathy
      (SE) we immunized Balb/c mice either intragastrically or intranasally (i.n.) with
      a recombinant PrP-fragment (PrP90-231) and cholera toxin (CT) adjuvant. Since
      PrP90-231 was rapidly digested in intestinal lavage, aprotinin was added to some
      vaccine formulations. While an anti-CT response was elicited via both routes,
      solely i.n. immunization without aprotinin induced PrP-specific sIgA. They
      recognize predominantly PrP-oligomers as the antigen was aggregated in the
      vaccine formulations. Challenge experiments showed that the immune response
      induced by our protocol could not prevent disease, but increases the median
      survival of the animals. We conclude that PrP-specific sIgA reduce the
      infectivity of the inoculum and that complete protection against transmission of
      SE should be achievable by optimized immunization regimens.

PMID- 16455169
TI  - Comparative immunogenicity of a PreS/S hepatitis B vaccine in non- and low
      responders to conventional vaccine.
AB  - Conventional hepatitis B vaccines do not elicit adequate antibody production in 5
      10% vaccinees. This trial tests the ability of a third-generation vaccine,
      containing PreS1 and PreS2 antigens in addition to the S antigen, to elicit
      seroprotective titres in documented non- and low-responders, compared with those
      to a conventional vaccine. In the primary population of non-responders (<10 IU/l
      anti-HBs antibodies after > or = 4 previous injections of conventional vaccine)
      an enhanced antibody response was seen to additional injections of the third
      generation vaccine compared with a conventional vaccine (absolute difference
      14.9%; P = 0.006). Enhanced antibody responses were also found in a population
      that included low responders.

PMID- 16455171
TI  - Regulatory objectivity and the generation and management of evidence in medicine.
AB  - The evolution of Western medicine since World War II has resulted in the
      emergence of new practices based on the direct interaction of biology and
      medicine. The post-war realignment of biology and medicine has been accompanied
      by the emergence of a new type of objectivity, regulatory objectivity, that is
      based on the systematic recourse to the collective production of evidence. Unlike
      forms of objectivity that emerged in earlier eras, regulatory objectivity
      consistently results in the production of conventions, sometimes tacit and
      unintentional but most often arrived at through concerted programs of action.
      These actions incorporate unprecedented levels of reflexivity, in the sense that
      biomedical practitioners in their debates and discussions take into account the
      conventional dimension of their endeavors. The conventions produced by regulatory
      objectivity create the conditions for a clinical objectivity that relies on the
      existence of entities and protocols produced and maintained far outside the
      intimate encounter between doctor and patient. By establishing endogenous forms
      of regulation, regulatory objectivity operates on a different plane and in a
      different mode from those suggested by analysts who treat all regulation as a
      form of rationalization imposed upon medicine from without.

PMID- 16455170
TI  - Potential of KM+ lectin in immunization against Leishmania amazonensis infection.
AB  - In the present study we evaluated Canavalia brasiliensis (ConBr), Pisum arvense
      (PAA) and Artocarpus integrifolia (KM+) lectins as immunostimulatory molecules in
      vaccination against Leishmania amazonensis infection. Although they induced IFN
      gamma production, the combination of the lectins with SLA antigen did not lead to
      lesion reduction. However, parasite load was largely reduced in mice immunized
      with KM+ lectin and SLA. KM+ induced a smaller inflammatory reaction in the air
      pouch model and was able to inhibit differentiation of dendritic cells (BMDC),
      but to induce maturation by enhancing the expression of MHC II, CD80 and CD86.
      These observations indicate the modulatory role of plant lectins in leishmaniasis
      vaccination may be related to their action on the initial innate response.

PMID- 16455172
TI  - Is coherent motion an appropriate test for magnocellular sensitivity?
AB  - The suggestion that coherent motion may serve as a test of magnocellular
      sensitivity is problematic. However, the nature of the problems depends on how
      the "magnocellular system" is defined. If this term is limited to subcortical
      entities, the problems are that subcortical neurons are not directionally
      selective, and that their receptive fields are too small to account for the
      spatial summation of coherent motion. If "magnocellular system" is defined to
      include cortical entities, such as area MT, one is faced with the fact that this
      definition itself is problematic as well as the problem that area MT is known to
      receive parvocellular and koniocellular inputs.

PMID- 16455173
TI  - High functioning children with autism spectrum disorder: a novel test of
      multitasking.
AB  - High functioning children with a diagnosis of autism or Asperger's syndrome (HF
      ASD) often experience difficulties organising goal-directed actions in their day
      to-day lives, requiring support to schedule daily activities. This study aimed to
      capture these everyday difficulties experimentally using multitasking, a
      methodology that taps into the cognitive processes necessary for successful goal
      directed activities in everyday life. We investigated multitasking in children
      with HF-ASD using a novel multitask test, the Battersea Multitask Paradigm.
      Thirty boys participated in the study, 14 with HF-ASD and 16 typically developing
      controls, matched for age and IQ. Group differences in multitasking were
      observed. Participants with HF-ASD were less efficient at planning, attempted
      fewer tasks, switched inflexibly between tasks and broke performance rules more
      frequently than controls.

PMID- 16455174
TI  - Finding a face in the crowd: testing the anger superiority effect in Asperger
      Syndrome.
AB  - Social threat captures attention and is processed rapidly and efficiently, with
      many lines of research showing involvement of the amygdala. Visual search
      paradigms looking at social threat have shown angry faces 'pop-out' in a crowd,
      compared to happy faces. Autism and Asperger Syndrome (AS) are neurodevelopmental
      conditions characterised by social deficits, abnormal face processing, and
      amygdala dysfunction. We tested adults with high-functioning autism (HFA) and AS
      using a facial visual search paradigm with schematic neutral and emotional faces.
      We found, contrary to predictions, that people with HFA/AS performed similarly to
      controls in many conditions. However, the effect was reduced in the HFA/AS group
      when using widely varying crowd sizes and when faces were inverted, suggesting a
      difference in face-processing style may be evident even with simple schematic
      faces. We conclude there are intact threat detection mechanisms in AS, under
      simple and predictable conditions, but that like other face-perception tasks, the
      visual search of threat faces task reveals atypical face-processing in HFA/AS.

PMID- 16455175
TI  - Is obsessive-compulsive disorder an anxiety disorder?
AB  - Obsessive-compulsive disorder (OCD) is classified as an anxiety disorder in the
      DSM-IV-TR [American Psychiatric Association, 2000. Diagnostic and statistical
      manual of mental disorders, Fourth ed., rev. Washington, DC: Author]; however,
      the notion of a spectrum of obsessive-compulsive (OC) related disorders that is
      comprised of such disparate disorders as OCD, body dysmorphic disorder, certain
      eating disorders, pathological gambling, and autism, is gaining acceptance. The
      fact that these disorders share obsessive-compulsive features and evidence
      similarities in patient characteristics, course, comorbidity, neurobiology, and
      treatment response raises the question of whether OCD is best conceptualized as
      an anxiety or an OC spectrum disorder. This article reviews evidence from
      comorbidity and family studies, as well as biological evidence related to
      neurocircuitry, neurotransmitter function, and pharmacologic treatment response
      that bear on this question. The implications of removing OCD from the anxiety
      disorders category and moving it to an OC spectrum disorders category, as is
      being proposed for the DSM-V, is discussed.

PMID- 16455176
TI  - Effects of an inspiratory impedance threshold device on blood pressure and short
      term survival in spontaneously breathing hypovolemic pigs.
AB  - BACKGROUND: The inspiratory impedance threshold device (ITD) has been shown to
      improve hemodynamic variables and survival outcomes during cardiopulmonary
      resuscitation in animals and humans. We hypothesized that use of an ITD, with a
      resistance of -10 cm H2O, will improve hemodynamics and short-term survival rates
      during hypovolemic hypotension in spontaneously breathing pigs. METHODS: Female
      farm pigs ( approximately 26 kg) were intubated and anesthetized with propofol
      with the dose adjusted to permit spontaneous respirations. They were bled to 50%
      of calculated blood volume through an arterial catheter and then prospectively
      randomized to either treatment with an ITD or observation alone. Arterial and
      intratracheal pressures as well as arterial blood gases were measured. After 90
      min the ITD was removed, normal saline was administered to all surviving animals,
      the anesthetic was discontinued, and animals were allowed to recover. Statistical
      analysis was performed with one-way repeated ANOVA and survival rates were
      calculated with Kaplan-Meier analysis. RESULTS: Treatment with the ITD resulted
      in lower intratracheal inspiratory pressure in the treatment group (-11+/-0.4
      mmHg versus -4+/-0.7 mmHg, respectively, P<0.005). Mean arterial pressure after
      30 min of treatment with the ITD was higher in the treatment group (61.1+/-5.5
      mmHg versus 37.4+/-2.1 mmHg, respectively, P<0.005). All pigs in the control
      group died within 65 min of the initial bleed, whereas 7/8 (87%) treated with an
      ITD survived for >90 min (P<0.001). During the recovery phase, 6/8 (75%) in the
      ITD group survived for >3h and awoke without neurological deficit; one surviving
      animal in the ITD group never woke up. Arterial oxygenation was not compromised
      in the ITD group. CONCLUSIONS: Use of an ITD improved blood pressure and short
      term survival rates in a spontaneously breathing porcine model of hypovolemic
      hypotension.

PMID- 16455177
TI  - Etiology of pediatric out-of-hospital cardiac arrest by coroner's diagnosis.
AB  - OBJECTIVES: To determine etiology of pediatric OHCA in a population-based sample
      from autopsy and coroner's diagnosis. DESIGN: As part of the Ontario Pre-hospital
      Advanced Life Support (OPALS) study, we conducted a prospective cohort study
      including children below age 19 years with OHCA in an 11-year period. Deaths were
      matched with provincial coroner's office records and autopsies and investigation
      notes were reviewed. RESULTS: From 1992 to 2002, there were 474 cardiac arrests
      in children below 19 years of age giving an annual incidence of 59.7 per million
      children. Mean age was 5.8 (S.D. 6.3), 43.0% were <1 year of age, males were
      59.1%. 25.1% were bystander witnessed and 20.3% received bystander CPR. 1.9%
      survived to discharge. Four hundred and thirty nine matched to coroner's office
      records. Annual incidence rates per million by age groups were: 175.0 (age 1-4
      years), 33.0 (age 5-14 years) and 61.6 (age 15-18). Annual incidence rates per
      million according to coroner's cause of death were: natural (26.2), accidental
      (17.4), suicide (3.7) and homicide (1.9). Post-mortem rate was 84.3% and Mean
      Injury Severity Score was 31.4 (S.D. 16.5). The commonest causes of natural death
      were SIDS (30.3%), cardiovascular (19.2) and respiratory (18.3%). The commonest
      causes of accidental death were drowning (27.5%), residential accidents (18.8%),
      fire (13.0%) and motor vehicle collisions (12.3%). CONCLUSION: The highest
      mortality rates were among children age <4 years. 52.6% of deaths were from
      'unnatural' causes (accidental, suicide, homicide, undetermined). Our findings
      will be useful for planning prevention, treatment and future research of
      pediatric OHCA.

PMID- 16455178
TI  - How safe are HEMS-programmes in Germany? A retrospective analysis.
AB  - INTRODUCTION: Recent accidents with helicopter emergency medical service (HEMS)
      aircraft raise the question how safe HEMS in Germany is and how accidents could
      be prevented. MATERIALS AND METHODS: We surveyed all German HEMS-programmes and
      reviewed the data of the German Aviation Authority regarding accidents with HEMS.
      RESULTS: An average German HEMS-programme encounters one accident leading to at
      least severe damage or loss of the helicopter in 26 operating years, one accident
      resulting in casualties in 65 operating years and one fatal accident in 111
      operating years. The major causes of accidents were obstacle strikes during
      landing at the scene. Flying in bad weather conditions and lack of discipline
      were other factors contributing to HEMS-accidents. CONCLUSION: HEMS-safety could
      be improved by special training programmes for pilots and HEMS-crewmembers to
      address the factors listed above. Safety training for doctors is recommended but
      we did not find support for the notion of changing the doctor's legal position of
      a passenger to a HEMS-crewmember.

PMID- 16455179
TI  - Complexation of norfloxacin with DNA in the presence of caffeine.
AB  - (1)H NMR spectroscopy (500 MHz) has been used to quantify the complexation of the
      antibacterial antibiotic Norfloxacin (NOR) with DNA in the presence of Caffeine
      (CAF). Separate studies have been made for the self-association of NOR, its
      hetero-association with CAF and complexation with a model self-complementary DNA
      tetramer, 5'-d(TpGpCpA), in order to determine the equilibrium parameters
      (induced chemical shifts, association constants, enthalpy and entropy) of the two
      component mixtures to aid the analysis of the three-component systems.
      Investigations of the self-association of NOR and its hetero-association with CAF
      show that the aggregation of NOR molecules and association with CAF in solution
      are driven by the stacking of aromatic chromophores. The complexation of NOR with
      d(TGCA) has been analysed in terms of intercalation with the double-stranded form
      and non-intercalative binding with the single-stranded form of DNA.
      Investigations of the competitive binding of NOR and CAF with DNA show that at
      physiological concentrations of NOR (muM) and CAF (mM) the dominant mechanism
      influencing the affinity of NOR with DNA is the displacement of bound NOR
      molecules from DNA due to CAF-DNA complexation (i.e. the protector action of
      Caffeine).

PMID- 16455180
TI  - One and two dimensional 1H and 13C high resolution NMR investigation of lariat
      ethers and their alkali metal ionic complexes: a more tangible evidence for the
      presence of less common C-H***O hydrogen bonds.
AB  - The possible existence of less common hydrogen bonds in three lariat ethers and
      their alkali-metal ionic complexes have been investigated with one- and two
      dimensional (1D and 2D) proton and carbon-13 high resolution liquid state NMR
      spectroscopy. The occurrence of hydrogen-bonding induced by the addition of metal
      ions has been identified with the observation of indirect dipolar coupling
      between the coupling partners involved in the hydrogen-bonding. The addition of
      metal ions, moreover, causes appreciable change of chemical shift of several
      protons and carbons. The chemical shift change depends on the ion radius, larger
      ions causing smaller change. Moreover, the change of chemical shift is in
      coincidence with the occurrence of hydrogen-bonding. The values of the coupling
      constants have been obtained for each of these hydrogen bonds and were used for
      evaluating the hydrogen-bond strength. An intriguing and surprising observation
      is that a C-H***O hydrogen bond identified in solution by this work was not found
      in the previous study with X-ray diffraction or other methods.

PMID- 16455181
TI  - Gene expression in normal urothelium depends on location within the bladder: a
      possible link to bladder carcinogenesis.
AB  - OBJECTIVES: Clinical studies have shown that more than 70% of primary bladder
      tumours arise in the area around the ureteric orifice. In this study a genomic
      approach was taken to explore the molecular mechanisms that may influence this
      phenomenon. METHODS: RNA was isolated from each individual normal ureteric
      orifice and the dome biopsy from 33 male patients. Equal amounts of the pooled
      ureteric orifice and dome mRNAs were labelled with Cy3 and Cy5, respectively
      before hybridising to the gene chip (UniGEM 2.0, Incyte Genomics Inc.,
      Wilmington, Delaware, USA). RESULTS: Significant changes (more than a twofold
      difference) in gene expression were observed in 3.1% (312) of the 10,176 gene
      array: 211 genes upregulated and 101 downregulated. Analysis of Cdc25B, TK1, PKM,
      and PDGFra with RT-PCR supported the reliability of the microarray result.
      Seladin-1 was the most upregulated gene in the ureteric orifice: 8.3-fold on the
      microarray and 11.4-fold by real time PCR. CONCLUSIONS: Overall, this study
      suggests significant altered gene expression between these two anatomically
      distinct areas of the normal human bladder. Of particular note is Seladin-1,
      whose significance in cancer is yet to be clarified. Further studies of the genes
      discovered by this work will help clarify which of these differences influence
      primary bladder carcinogenesis.

PMID- 16455182
TI  - A simple design for a stoma flange cutter.
AB  - Several stoma flange cutters have been described, however it appears that there
      is limited awareness of their existence by doctors, stoma care nurses or
      patients. In this article a simple design for a stoma flange cutter is described.

PMID- 16455183
TI  - Impact of a multidisciplinary continuous quality improvement program on the
      positive surgical margin rate after laparoscopic radical prostatectomy.
AB  - OBJECTIVE: Outcome after radical prostatectomy is highly sensitive to fine
      nuances in the surgical techniques. We sought to determine the impact of a
      process of continuous control and monitoring on the positive surgical margin rate
      in a contemporary series of laparoscopic radical prostatectomy. METHODS: Between
      January 2003 and October 2004, 301 men underwent laparoscopic radical
      prostatectomy for clinically localized prostate cancer (cT1-cT3a). A weekly case
      review conference involving surgeons, radiologists, and uropathologists was held
      to discuss the preoperative, intraoperative, and pathologic findings of
      significant cases. We analyzed the trend of positive surgical margins and
      compared the clinical and detailed pathologic characteristics of the cancer
      during the study period. RESULTS: We created logistic regression models with
      positive margin as the dependent variable and surgical experience as the
      predictor, adjusting for possible secular changes in disease severity (prostate
      specific antigen, pathologic stage, and Gleason grade). There was a decrease in
      the rate of surgical margins: odds ratio 0.68/100 patients treated (95%
      confidence interval [CI] 0.44, 1.05; p=0.08). The predicted probability for a
      positive surgical margin falls from 17.3% for the first patient to 7.5% for the
      301st. These values are close to the observed rates for the first and last 50
      patients. There was no important change in surgical risk over the course of the
      study, and the rate of nerve sparing remained stable throughout the study period.
      CONCLUSIONS: In this contemporary series, which is unaffected by downward stage
      migration, the decreasing rate of positive surgical margins can be explained by
      subtle surgical technique modifications and a continuous multidepartmental effort
      for quality improvement.

PMID- 16455184
TI  - Facilitatory neuromodulative effect of duloxetine on pudendal motor neurons
      controlling the urethral pressure: a functional urodynamic study in healthy
      women.
AB  - OBJECTIVE: The aim of this functional urodynamic experiment in healthy women was
      to study the effect of duloxetine, which is a combined serotonin and
      norepinephrine (5-HT/NE) reuptake inhibitor, on urethral resting pressure,
      excitability of pudendal motor neurons, and urethral sphincter contractility.
      METHODS: In 11 healthy female subjects three baseline urethral pressure profiles
      (UPPs) were obtained to study resting pressure. Afterward the individual motor
      threshold (MT) for external urethral sphincter (EUS) contraction in response to
      transcranial magnetic stimulation (TMS) was determined to study the excitability
      of pudendal motor neurons. Another three UPPs were recorded while sacral root
      magnetic stimulation (SMS) was performed to evoke reproducible urethral
      contractions to study urethral sphincter contractility. Then the women received
      40 mg duloxetine and the protocol was repeated 4 h after drug administration. The
      resting pressure values, MT values following TMS, and the EUS pressure amplitudes
      in response to SMS obtained at baseline were statistically compared to the
      corresponding values at follow-up after duloxetine. RESULTS: Oral administration
      of duloxetine significantly lowered MT for EUS contraction in response to TMS
      (p=0.013). In addition, duloxetine significantly increased EUS pressure
      amplitudes in response to SMS (p=0.0007, 5 of 11 subjects evaluated) but did not
      change urethral resting pressures. CONCLUSIONS: This is the first functional,
      urodynamic controlled study to show that the combined 5-HT/NE reuptake inhibitor
      duloxetine has a significant effect on the excitability of pudendal motor neurons
      and on urethral sphincter contractility in healthy women in vivo but no
      significant effect on urethral resting tone. Our data confirm a facilitatory
      neuromodulative effect of duloxetine on sphincter motor neurons in humans.

PMID- 16455185
TI  - The importance of cyclooxygenase in carcinogenesis: is it a therapeutic target?

PMID- 16455186
TI  - Diclofenac for treatment of nocturia caused by nocturnal polyuria: a prospective,
      randomised, double-blind, placebo-controlled crossover study.
AB  - OBJECTIVES: To investigate the efficacy of diclofenac 50 mg enteric-coated tablet
      (Non-Steroidal Anti-Inflammatory Drug) in the treatment of nocturnal polyuria.
      MATERIALS AND METHODS: 26 patients (20 male and 6 female) with a mean age of 72
      years (range 52-90) diagnosed with nocturnal polyuria were recruited. The study
      period comprised 2 weeks of either placebo or active medication taken at 2100 h.
      Following one-week rest period, patients were crossed over to the other
      medication for a further 2 weeks. Frequency volume charts were completed during
      the second week of each of the two study periods along with feedback forms to
      assess any subjective improvement in symptoms during each of the study periods.
      RESULTS: A significant improvement in the symptoms was noted for diclofenac when
      compared with the placebo. The mean nocturnal frequency decreased from 2.7 to 2.3
      (p<0.004) and the mean ratio of night-time to 24 h urine volume decreased from
      44% to 39% (p<0.001). No significant side effects were reported. CONCLUSIONS:
      NSAIDs are effective in the treatment of nocturnal polyuria causing a decrease in
      nocturnal frequency with subjective symptom improvement. Our study suggests a
      novel treatment option for this common condition.

PMID- 16455190
TI  - Open to debate. The motion: prevention of prostate cancer with a 5alpha-reductase
      inhibitor is feasible.

PMID- 16455191
TI  - Non-genomic ecdysone effects and the invertebrate nuclear steroid hormone
      receptor EcR--new role for an "old" receptor?
AB  - The ecdysteroids (Ec), invertebrate steroid hormones, elicit genomic but also non
      genomic effects. By analogy to vertebrates, non-genomic responses towards Ec may
      be mediated not only by distinct membrane-integrated but also by membrane
      associated receptors like the classical nuclear ecdysteroid receptor (EcR) of
      arthropods. This is supported by a comparison of physiological properties between
      invertebrate and vertebrate steroid hormone systems and recent findings on the
      subcellular localization of EcR. The measured or predicted high degree of
      conformational flexibility of both Ec and the ligand binding domain (LBD) of EcR
      give rise to a conformational compatibility model: the compatibility between
      conformations of the cognate receptor's ligand binding domain and structures or
      conformations of the ligand would determine their interaction and eventually the
      initiation of genomic versus non-genomic pathways. This model could also explain
      why specific non-genomic effects are generally not observed with non-steroidal
      agonists of the bisacylhydrazine group.

PMID- 16455192
TI  - Host macrophages produce diacetylspermine related with tumorigenesis.
AB  - Diacetylpolyamines (DAPs) are novel, promising tumor related markers, but the
      mechanism sustaining their good sensitivity and specificity is not known. This
      investigation was conducted on the production mechanism of DAPs, using
      (C57BL/6NxDBA/2N)F(1) mice and the P388D(1) (lymphoid) tumor system. Spleen
      adherent cells from mice injected with thioglycollate produced N(1),N(12)
      diacetylspermine (DAM) in co-culture with P388D(1) cells. Macrophages among
      peritoneal exuded cells also produced DAM actively, while granulocytes, another
      innate immune cell, did not. The participation of macrophages in vivo was
      confirmed by depletion experiments using dichloromethylene diphosphonate
      liposomes. The supply of exogenous spermine and a deficiency of glucose, which
      tend to occur with tumorigenesis, resulted in an explosion of the production of
      DAM by macrophages. The number of macrophages required for the elevation of DAM
      for a diagnosis in humans was estimated at less than 4.2 x 10(8). The mechanism
      and productivity studied in this work support the superiority of DAM as a tumor
      related marker. Diacetylation may relate to the depression of macrophage function
      by spermine.

PMID- 16455193
TI  - Human urinary bladder cancer T24 cells are susceptible to the Antrodia camphorata
      extracts.
AB  - Bladder cancer has been cited to result from the neoplastic lesion with
      environmental and/or occupational factors identified as causatives. Transitional
      cell carcinoma (TCC) is the most common type of bladder cancer. Most of the
      bladder cancer patients die from the invasive, metastatic TCC that has turned out
      to be resistant to chemotherapy. T24 cells, a cell line established from a human
      urinary bladder cancer patient, are high-grade and invasive TCC. T24 cells were
      found very susceptible to ACCE at concentration of 50 microg/mL. MTT assay showed
      that the cell growth and proliferation were inhibited to 50% of the control when
      treated with ACCE for 72 h, at which the cell proliferation suppressing rate
      revealed -4.4 x 10(3)cells/microg per day. Comparing the expressions of the cell
      cycle biomarkers Cdc2 and Cyclin B1 by the western blot analysis, a phase G(2)M
      arrest was confirmed. Both the wound scratch assay and the transwell motility
      assay indicated that ACCE was very effective anti-metastatic against T24 cells.
      Furthermore, the active form of matrix metalloproteinase-9 (MMP-9) was also found
      totally suppressed as revealed by zymography at 72 h post-incubation with ACCE,
      while the light and electron microscopic images have apparently revealed cell
      membrane damages on T24 cells when treated with ACCE (50 microg/mL). Moreover,
      both the wound scratch and the transwell assays have demonstrated the migration
      capability of T24 cells has been significantly retarded to 1.5-fold at same
      dosage of ACCE used. In conclusion, ACCE is a good anti-cancer agent, being
      effective in inducing phase G(2)M arrest, acting as an anti-proliferative, and an
      anti-metastatic agent against bladder cancer cell T24 cells.

PMID- 16455194
TI  - Involvement of mitogen-activated protein kinases and protein kinase C in
      regulation of antioxidant response element activity in human keratinocytes.
AB  - Antioxidant response element (ARE) is a unique cis-acting regulatory sequence
      located in the upstream regions of many genes encoding
      anticarcinogenic/antioxidant proteins. Induction of ARE dependent genes plays an
      important role in protection of cells against oxidative damage. However, the
      signaling mechanism(s) involved in regulating transcription of ARE dependent gene
      expression has not been clearly defined. In this study, we identified protein
      kinases that are involved in regulation of ARE activity by using specific
      pharmacological inhibitors of protein kinases in engineered human HaCaT
      keratinocytes, which stably express the ARE-driven green fluorescent protein
      (GFP) as a reporter. When HaCaT/GFP cells were treated with tert
      butylhydroquinone (tBHQ), a well-known ARE activator, GFP expression was up
      regulated in time and dose dependent manner, indicating that tBHQ activates the
      ARE in these cells. Treatment of cells with SB202190 (a specific inhibitor of
      p38), staurosporine (a wide-spectrum inhibitor of PKC) or rottlerin (a specific
      inhibitor of PKCdelta) all augmented ARE activation by tBHQ. These results
      suggest that p38 and PKC, especially PKCdelta, play inhibitory roles in ARE
      activation in human keratinocytes. Furthermore, UVB irradiation minimally affects
      the basal ARE activity but significantly suppresses tBHQ induced ARE activation,
      indicating that UVB irradiation interrupts tBHQ signaling. Interestingly,
      treatment of HaCaT/GFP cells with SP600125 (a specific inhibitor of JNK) could
      reverse UVB mediated suppression of ARE activation by tBHQ. This suggests that
      the suppressive effect of UVB on ARE activation by tBHQ is mediated by a JNK
      pathway(s). These findings provide useful information for developing novel
      strategies for skin cancer chemoprotection through ARE activation.

PMID- 16455195
TI  - BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk
      of carrying mutations.
AB  - We analyzed the mutation spectrum of BRCA1 and BRCA2 genes in 354 Korean breast
      cancer patients. Overall, 40 patients carried 25 distinct BRCA1/2 mutations
      including 12 novel mutations. Seven district mutations were found in multiple
      unrelated patients, with the BRCA2 c.7480C>T mutation detected in eight unrelated
      patients, accounting for 50% of the mutations detected in BRCA2. The large number
      (25/40, 62.5%) of recurrent mutations suggests the possibility of developing a
      simple screening test for these mutations. The frequency of mutations was related
      to the number and kinds of risk factors, varying from 10.4 to 25% in the five
      major risk factor groups. The frequency of BRCA mutations in patients with two or
      more risk factors was markedly higher than that in patients with one risk factor.

PMID- 16455197
TI  - Integrated treatment of PAH contaminated soil by soil washing, ozonation and
      biological treatment.
AB  - The aim of the study was to optimise three different treatment methods and to
      find out if the integration of soil washing, ozonation and biological treatment
      could be a feasible method for the remediation of aged oil contaminated with
      PAHs. Three different ozone doses and soil washing were studied in different pHs
      in order to assess their effect to the degradation and enhancement of
      biodegradability of PAH in the soil and water phase. Main target of the study was
      to find out a method with which the PAH concentrations could be decreased below
      the Finnish guideline level for total PAHs. In this case, the initial
      concentration of PAHs was 1200 mg kg(-1) and therefore almost 85% degradation of
      PAHs was required. Any of the methods studied was not able to reach this target
      level alone, but by several combinations of the methods studied achieved 90%
      reduction of PAHs. The consumption of ozone was 5-10 times lower in the
      integrated treatments of soil washing, ozonation and biological treatment than
      without prewashing.

PMID- 16455196
TI  - Effects of lipid association on lomustine (CCNU) administered intracerebrally to
      syngeneic 36B-10 rat brain tumors.
AB  - A syngeneic, intracerebral rat brain tumor model was developed and characterized
      and then used to evaluate the therapeutic enhancement of lipid-associated 1-(2
      chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). The Fisher rat glioma cell 36B-10
      (100,000-500,000 cells) was implanted intracranially to Fisher F-344 rats into
      the caudate nucleus. Animals treated with lipid-associated CCNU showed a 2- to 10
      fold decrease in tumor size compared with animals treated with free CCNU,
      indicating that lipid association increases the therapeutic index of
      intracerebral CCNU treatment. Moreover, the syngeneic rat brain tumor model may
      be useful for evaluation of other therapeutic modalities.

PMID- 16455198
TI  - Oxidation of various reactive dyes with in situ electro-generated active chlorine
      for textile dyeing industry wastewater treatment.
AB  - The present investigation revealed that all the reactive dyes were degraded in
      chlorine mediated electrochemical oxidation. Titanium based dimensionally stable
      anode (DSA) was used for in situ generation of chlorine in the dye solution. All
      classes of reactive dyes (100 mg/L) showed a complete color removal at a
      supporting electrolyte concentration of 1.5 g/L NaCl and 36.1 mA/cm(2) current
      density. The chemical oxygen demand (COD) and total organic carbon (TOC) removals
      were from 39.5 to 82.8% and from 11.3 to 44.7%, respectively, for different
      reactive dyes. It can be concluded in general that the triazine containing higher
      molecular weight diazo compounds takes more time for complete de-colorization
      than the mono azo or anthraquinone containing dye compounds. The degradation rate
      of mixed dye compounds was affected by reaction temperature, current density,
      NaCl concentration and initial dye concentration. However, the initial pH of the
      dye solution ranging from 4.3 to 9.4 did not show significant effect on de
      colorization. A complete color removal with 73.5% COD and 32.8% TOC removals were
      obtained for mixed reactive dyes (200 mg/L) at the end of 120 min of electrolysis
      under the optimum operating conditions of 4 g/L NaCl concentration and 72.2
      mA/cm(2) current density.

PMID- 16455200
TI  - The insensate burn: pain insensitivity syndrome.

PMID- 16455199
TI  - Adult bone marrow cells differentiate into neural phenotypes and improve
      functional recovery in rats following traumatic brain injury.
AB  - This study aims to investigate the therapeutic potential of adult bone marrow
      stromal cells (BMSCs). Exposed to a cocktail of induction medium, some BMSCs
      could differentiate into cell types with phenotypes of neural lineages in vitro.
      These cells expressed neural markers nestin, GFAP, 68-kDa neurofilament and beta
      tubulin III as detected by immunohistochemistry and RT-PCR. Fluorescence-labeled
      cells were injected intravenously at 72 h after traumatic brain injury.
      Transplanted cells survived and migrated to the ipsilateral cerebral cortex at
      different time points after injection. They were immunopositive for neuronal
      marker MAP-2, oligodendrocyte marker CNPase, astrocytic maker GFAP or microglial
      marker OX-42 in vivo. In rats receiving BMSC transplants, there were significant
      improvements in motor and neurological functions when compared with the control
      groups. Hence, the therapeutic potential of BMSCs for traumatic brain injury is
      further amplified.

PMID- 16455201
TI  - Eyelid reconstruction with acellular human dermal allograft after chemical and
      thermal burns.
AB  - OBJECTIVE: To evaluate the efficacy of eyelid reconstruction with acellular
      dermal allograft in patients with eyelid defect after chemical and thermal burns.
      METHOD: Eyelid reconstruction was performed in 15 eyelids of 13 patients during
      the period of June 2001-October 2004 by a single senior surgeon (Chen). Among
      them five patients had thermal burns, and eight patients had chemical burns. The
      acellular dermal allograft was used as a tarsus substitute that was sutured into
      the place between the levator aponeurosis in upper lid or retractor in lower
      eyelid and the remaining tarsus. RESULTS: After a mean follow-up of 9 months,
      satisfactory function and cosmesis were obtained. No implant rejection or severe
      complications were observed. CONCLUSION: Acellular dermal allograft may be used
      safely as a posterior lamellar spacer graft after chemical and thermal burns; the
      allograft appears to be biocompatible and does not aggravate the inflammation in
      the injured eyelid.

PMID- 16455202
TI  - Evaluation of a bi-layer wound dressing for burn care. II. In vitro and in vivo
      bactericidal properties.
AB  - We have recently designed a medicated bi-layer wound dressing to address the key
      requirements for treating external, contaminated war wounds. This study assessed
      the in vitro and in vivo bactericidal efficacies of the DRDC
      hydrogel/polyurethane wound dressing. Chloramphenicol- and chlorhexidine-loaded
      DRDC dressings produced significantly larger zones of inhibition against
      Pseudomonas aeruginosa than the other medicated dressings for 4 d. Chlorhexidine
      loaded Allevyn and Hydrasorb remained bactericidal for 48 h only. Chloramphenicol
      loaded Hydrasorb and Allevyn remained bactericidal for 1 and 3 d, respectively.
      Ps. aeruginosa and Staphylococcus epidermidis counts in wounds treated with
      chlorhexidine- and chloramphenicol-loaded DRDC dressings for 24 h were 1-3-log
      lower than those of control wounds. While Ps. aeruginosa counts in the wounds on
      day 4 were comparable following daily changes of either antiseptic-loaded
      dressings, chlorhexidine showed a 75% greater bactericidal efficacy against
      Staph. epidermidis than chloramphenicol. Though increasing the frequency of
      dressing changes led to a greater reduction in the wound bacterial load, the
      contamination levels of all antiseptic-treated wounds remained below 10(5) CFU/g
      of wound. Cerium nitrate-loaded dressings did not exert any bactericidal effect,
      irrespective of the experimental conditions. These data show that the DRDC
      dressing is effective in delivering medications, such as an antimicrobial agent,
      to the wound bed.

PMID- 16455203
TI  - Keratin expression in cultured skin substitutes suggests that the
      hyperproliferative phenotype observed in vitro is normalized after grafting.
AB  - Cultured skin substitutes, consisting of fibroblasts and keratinocytes in a
      biopolymer matrix, are an adjunctive treatment for full thickness burn wounds.
      Previous studies revealed that cultured skin substitutes in vitro exhibit a gene
      expression profile similar to hyperproliferative skin or wounded normal skin. In
      the present study, we sought to determine whether this hyperproliferative
      phenotype is maintained after healing of grafted cultured skin in vivo.
      Immunohistochemistry was used to localize multiple keratin proteins in native
      human skin, and in cultured skin substitutes in vitro and after grafting to
      athymic mice. Keratin 6, keratin 16, and keratin 17, which are known to be
      upregulated during keratinocyte activation and in hyperproliferative epidermis,
      were highly expressed in cultured skin substitutes in vitro. These proteins were
      low or undetectable in native human skin, and were reduced in cultured skin after
      grafting. Conversely, keratin 15, which is downregulated in activated
      keratinocytes, was not detected in cultured skin substitutes in vitro but was
      upregulated after grafting to mice. The results confirm previous observations
      suggesting a hyperproliferative or activated phenotype in cultured skin
      substitutes in vitro, similar to wounded native skin. After grafting to athymic
      mice, the expression patterns suggest a normalization of cultured skin
      substitutes to a phenotype more closely resembling uninjured human skin.

PMID- 16455204
TI  - No cancer in cancers: evolutionary trade-off between successful viviparity and
      tumor escape from the adaptive immune system.
AB  - Some invertebrate species including the king crab and king squid enjoy relatively
      long lives of up to 20 years. Nevertheless, there are few reports of malignancies
      among invertebrate animals while there are many such reports in lower vertebrates
      such as in fishes, amphibians, and reptiles. Viviparity is characteristic of most
      mammalian species, although it has been observed in both vertebrate and non
      vertebrate species. As adaptive immune responses evolved among the cartilaginous
      fishes by virtue of gene duplication, all viviparous vertebrates cope with
      specific immune responses to reject the fetal allograft. The escape mechanisms
      employed by both human and animal malignancies share common properties, which are
      also employed by feto-placental units, such as the expression of non-classical
      major histocompatibility antigens (HLA-E, HLA-F, and HLA-G in humans),
      accumulation of regulatory T cells, Th2-directed immune responses, Fas/FasL-
      and/or PD-1/PD-L1-induced apoptosis, and the expression of indoleamine 2, 3
      dioxygenase which starves the local tryptophan supply that is indispensable for
      an effective cytotoxic T cells response. In humans, a single cancer cell requires
      1-10 years to develop into a clinically remarkable tumor. For cancer cells, the
      genes encoding the immunoregulatory mechanisms employed by feto-placental units
      could be of value for escaping the host immune system. Taken together, these
      observations support the author's hypothesis that the evolution of viviparity
      resulted in an evolutionary trade-off that may have increased susceptibility to
      malignancies.

PMID- 16455205
TI  - Globalization in science education: an inevitable and beneficial trend.
AB  - Globalization is one aspect of the larger phenomenon of modernization, which
      describes societies characterized by progressive growth in the complexity of
      communications. Despite its inevitable problems, globalization is a generally
      desirable phenomenon, since it enables increased efficiency, effectiveness and
      capability of societies and thereby, potentially benefits most people most of the
      time. Scientific research was one of the first global communication systems,
      especially at its most advanced levels. And high quality scientific education at
      the post-doctoral level is also now essentially global. The next steps will be
      for lower level science education - at doctoral, undergraduate, and even school
      teaching levels - to become progressively globalized. This phenomenon is already
      happening in the mathematical and quantitative sciences, and will probably spread
      to include other kinds of science. But to be efficient requires the development
      of a trading medium of internationally standardized and quantitative educational
      credits - for instance, standard certificates, objective comparative
      examinations, and a hierarchical qualifications structure (which will almost
      certainly be based on the United States system). Globalized education also
      requires a common language for organizational communications, which is already in
      place for the quantitative and mathematical sciences, and will be increasingly
      the case as competence in a simplified form of international scientific English
      becomes more universal. As such a global science education system grows there
      will be increased competition and migration of teachers and students. The law of
      comparative advantage suggests that such mobility will encourage societies to
      specialize in what they do best. For example, some countries (even among wealthy
      nations) may provide little advanced scientific education, and import the
      necessary expertise from abroad - this situation seems to be developing in
      Germany and France, who lack any top-quality research universities. Conversely,
      just a few countries may provide the bulk of advanced science education teaching 
      as well as applied and pure research personnel - for the rest of the world:
      potentially China and India might supply most of world's mathematical expertise.
      In conclusion, there are two complementary aspects to the globalization of
      science education: these are standardization and specialization. We anticipate a
      simultaneous trend towards international convergence of basic educational
      structures, certificates and English usage; with increasing national
      differentiation of specialist educational functions.

PMID- 16455206
TI  - Botulinum toxin: a novel therapeutic option for bronchial asthma?
AB  - Two components are essential for the development of an attack of bronchial
      asthma: inflammation and bronchoconstriction, the latter being mediated by smooth
      muscle contraction. Despite the efficacy of chronic therapy, many asthmatics
      relapse. Measures to inhibit contraction of the airway smooth muscle, such as
      vagotomy and thermoablation, may decrease the bronchoconstrictor component of the
      asthma attack and help to decrease morbidity and mortality from the disease.
      Botulinum toxin acts to weaken skeletal and smooth muscle by preventing the
      docking of the acetylcholine vesicle on the inner surface of the presynaptic
      membrane, thus causing chemical denervation and paresis of skeletal or smooth
      muscle. We explore the possibility that administration of botulinum toxin may
      achieve the same effect in bronchial asthma and examine the evidence to support
      this hypothesis.

PMID- 16455207
TI  - Lithium: a potential treatment for hyper-IgE syndrome.

PMID- 16455208
TI  - Dopamine and the pathophysiology of suicidal behavior in alcoholism.

PMID- 16455209
TI  - Health maintenance and screening in breast cancer survivors in the United States.
AB  - BACKGROUND: The general health maintenance and follow-up of breast cancer
      survivors has not been well-studied. In a population-based sample we sought to
      investigate the health practices of breast cancer survivors and to compare rates
      of screening to women with no history of breast cancer. METHODS: Subjects were
      participants of the medical expenditure survey in the years 1996 and 1998, years
      for which information on screening were available. We used a matched cohort
      design. Breast cancer survivors aged 40 and older were matched (on age and
      race/ethnicity) to women with no breast cancer history. We performed logistic
      regression to estimate the odds of receiving appropriate health care services in
      breast cancer survivors versus women with no breast cancer history. In addition,
      we examined demographic and socioeconomic differences between breast cancer
      survivors who reported appropriate screening and survivors who had inadequate
      screening. RESULTS: A small minority of breast cancer survivors report inadequate
      mammography (18%) and clinical breast exam (12%) follow-up. A significant portion
      of breast cancer survivors report inadequate screening for Pap smear (40%),
      general physical exam (GPE) (30%) and flu shot (33%). The odds of receiving
      appropriate screening were higher in survivors versus matched women for
      mammography, clinical breast and cholesterol screening. There were no differences
      for other screening. Across all health maintenance and screening practices,
      breast cancer survivors who did not receive appropriate screening were less
      likely to have private insurance, to be married and to be above the mean income
      level, though these differences were non-significant. CONCLUSIONS: Although
      survivors report high levels of screening, a small minority of women report
      inadequate mammography and clinical breast exam follow-up which is concerning
      given their risk of recurrence and second primary breast cancer. Additionally, a
      significant portion of survivors report inadequate screening for general health
      maintenance issues. Demographic and socioeconomic factors were associated with
      lower screening rates. However, the deficits in screening among breast cancer
      survivors appears to be smaller compared to women in the general population.

PMID- 16455210
TI  - Disseminated, lethal prostate cancer during human immunodeficiency virus
      infection presenting with non-specific features. Open questions for urologists,
      oncologists, and infectious disease specialists.
AB  - INTRODUCTION: Prostate cancer is a very infrequent occurrence in persons aged 55
      years or less, and it has been rarely reported in HIV-infected patients (10
      overall cases so far); therefore, an increased incidence compared with the
      general population has not been established, although a younger age seems more
      frequent among population with HIV disease. CASE REPORT: We report a case of
      metastatic prostate cancer occurred in a 53-year-old HIV-infected man, admitted
      due to non-specific signs, and symptoms: impaired general conditions, fever,
      weight loss, fatigue, and exertional dyspnea. A remarkable anemia and an aortic
      systolic murmur were the prominent initial findings, while AIDS-related
      conditions were not suspected due to a sustained CD4+ count and a contained
      viremia, which never required antiretroviral therapy. Repeated red blood cell
      transfusions and an empiric, combined antimicrobial therapy were promptly carried
      out, under the suspicion of infectious endocarditis, but no appreciable
      improvement of clinical conditions was achieved. Subsequently, our patient
      complained not only of an increasingly severe pain at the root of his left thigh,
      together with overcoming dysuria and urgency, but also urinary tract infection
      that was rapidly ruled out. During the diagnostic workup for an HIV-associated
      fever of undetermined origin, a bone marrow biopsy disclosed a metastatic
      prostatic cancer, with elevated prostate specific antigen (PSA) and acid
      phosphate levels. An abdominal-pelvic ultrasonography and computerized
      tomographic scan allowed to detect a dyshomogeneous endopelvic expansive mass
      with extrinsic compression of the urinary bladder, and involvement of the last
      lumbar vertebra, large portions of pelvis, and the proximal epiphysis of the
      right femur. A skeleton scintigraphy pointed out multiple hypercaptation (areas
      of concentrated traces of radioactivity) areas with involvement of cranial,
      cervical, dorsal, lumbar, and sacral vertebrae, as well as the pelvis and upper
      portions of both femurs. Despite therapeutic attempts, our patient deceased after
      seven weeks due to an overwhelming disseminated intravascular coagulation (DIC).
      CONCLUSIONS: The non-specific clinical presentation of our case (mimicking other
      generalized or focal illnesses), and the final, lethal complication (DIC) pose
      striking problems related to the differential diagnosis during HIV disease, while
      the rapid evolution into an advanced, complicated, and widely metastatic disease
      with extensive bone marrow invasion which preceded the appearance of local signs
      symptoms, and the lethal overwhelming DIC, deserves attention by specialists who
      care for HIV-infected subjects.

PMID- 16455211
TI  - Lifetime psychiatric comorbidity of alcohol dependence and bulimia nervosa in
      women.
AB  - Previous work from our group revealed two groups of women with bulimia nervosa
      (BN), one with, and one without alcohol dependence (AD). The current study sought
      to determine whether women with lifetime BN and AD (BN+AD+) were more similar to
      women with BN and no AD (BN+AD-) or to women with AD and no BN (BN-AD+) in terms
      of lifetime psychiatric comorbidity and psychological functioning. Data on BN and
      AD from 407 female relatives in a family study of alcoholism were used to create
      three mutually exclusive groups: BN+AD+ (n=30), BN+AD- (n=55), and BN-AD+
      (n=322). Bivariate analyses revealed fewer differences between BN+AD+ and BN-AD+
      women than between BN+AD+ and BN+AD- women. BN+AD+ women were more likely than
      BN+AD- women to have drug dependence, conduct disorder, and suicidality, and were
      more likely to have major depression, lower GAF scores, and to engage in unsafe
      sex than both BN+AD- and BN-AD+ women. After adjusting for other psychopathology
      and demographic variables, BN+AD+ women were more likely than BN+AD- women to
      have major depression, drug dependence, and tobacco dependence and more likely
      than BN-AD+ women to have major depression and obsessive-compulsive disorder.
      These results suggest that BN+AD+ women exhibit more severe psychopathology than
      either BN+AD- or BN-AD+ women and may represent a distinct subgroup within
      bulimia nervosa or alcohol dependence.

PMID- 16455212
TI  - Repetitive DNA in tropical tasar silkworm Antheraea mylitta.
AB  - Antheraea mylitta is an endemic insect species producing the world famous tasar
      silk. Its populations occupying different ecological and geographical regions
      show certain degree of phenotypic variability for which they are known as 'eco
      races'. In order to understand the genetic variability and phylogenetic
      relationship among the different eco-races we characterized a repetitive TaqI
      genomic DNA fragment as a genetic marker. The sequence analysis and Southern
      hybridization show the repetitive nature of TaqI DNA fragment, designated as A.
      mylitta TaqI family repeat, AmTFR. The PCR amplification of AmTFR reveals its
      presence in all the tested eco-races of tasar silkworm and some other silk
      producing insects. The AmTFR is evenly distributed in all 31 meiotic metaphase I
      chromosomes as observed by fluorescent in situ hybridization. The AmTFR based
      phylogenetic analysis of the eco-races is not congruent with the morphological
      variations and their geographical distribution.

PMID- 16455213
TI  - Antibacterial activity of cefquinome against equine bacterial pathogens.
AB  - Cefquinome is known for its use as an antibacterial drug in cattle and pigs. The
      objective of this study was to evaluate the antibacterial activity of cefquinome
      against equine pathogenic bacteria. The minimum inhibitory concentration (MIC) of
      cefquinome was determined for a total of 205 strains, which had recently been
      isolated in Europe from diseased horses (respiratory infection, foal
      septicaemia). The bactericidal activity was tested against 19 strains using the
      time killing method. The post-antibiotic effect (PAE) and post-antibiotic sub-MIC
      effect (PA SME) were determined against 12 strains. Cefquinome showed high
      activity against Actinobacillus equuli and streptococci (MIC(90) of 0.016 and
      0.032microg/mL), Enterobacteriaceae (MIC(90)=0.125microg/mL) and staphylococci
      (MIC(90)=0.5microg/mL). The activity was limited against Rhodococcus spp. and
      Pseudomonas spp. Cefquinome was shown to be a time dependent bactericidal
      antibiotic against the target pathogens, killing occurring at a concentration
      close to the MIC. A PAE of 0.5-10h was calculated against streptococci whereas no
      PAE was observed for Escherichia coli. A longer PA SME was determined for
      streptococci (3.3 to >24h with a killing effect) and E. coli (0.5-13.9h).
      Cefquinome was shown to have a broad spectrum of activity which covers many
      equine pathogens.

PMID- 16455214
TI  - Biopharmaceutic and pharmacokinetic studies following the oral administration of
      sodium salicylate in oily and aqueous vehicles to rabbit.
AB  - The pharmacokinetic parameters, i.e. peak concentration (c(max)); peak time
      (t(max)); area under the curve (AUC); elimination rate constant (k); absorption
      rate constant (k(a)); Drug clearance (cl(t)), and the volume of distribution
      (v(d)) of sodium salicylate administered in fractionated coconut oil (FCO) have
      been compared with that from an aqueous and glycerin vehicles using a three-way
      crossover study in 12 rabbits. The results of the study show that all of the
      pharmacokinetic parameters tested differ significantly when administered in oily
      rather than aqueous or glycerin vehicles. No statistically significant difference
      was found between any of the above mentioned parameters when comparison was made
      between aqueous and glycerin formulations. The results indicate that sodium
      salicylate is absorbed at a lower rate but to a greater extent from oily
      formulation. Possible reasons for these differences are discussed and is
      suggested, therefore, that the oily formulation might be used as a sustained
      release preparation.

PMID- 16455215
TI  - Betamethasone-in-cyclodextrin-in-liposome: the effect of cyclodextrins on
      encapsulation efficiency and release kinetics.
AB  - Lipophilic drugs have limited solubility in phospholipid systems, hence maximum
      entrapment levels in liposomes are known to be low. "Drugs-in-cyclodextrin-in
      liposome" systems were previously proposed to overcome this drawback but studies
      were limited to betaCD and HPbetaCD. In some cases, other cyclodextrins may be
      more interesting than betaCD or HPbetaCD, such as methylated cyclodextrins.
      However, these cyclodextrins are known to extract lipid components from the lipid
      membrane, which may destabilize liposomes. We tested the influence of several
      cyclodextrins (betaCD, gammaCD, Dimeb, Trimeb, Crysmeb, Rameb, HPbetaCD and
      HPgammaCD) on the aqueous solubility of betamethasone by phase solubility
      diagrams and on the encapsulation efficiency in liposomes. The release kinetics
      of betamethasone was studied using Franz diffusion cells. We showed that release
      kinetics are directly correlated with encapsulation efficiency, which is closely
      related to betamethasone concentration in cyclodextrin complex solution. No
      liposome destruction was observed, even with the testing of methylated
      cyclodextrins at the highest concentration (40 mM). This can be explained by the
      fact that these cyclodextrins have a higher affinity for betamethasone than for
      cholesterol. This was proved by the comparison of phase solubility diagrams of
      both betamethasone and cholesterol.

PMID- 16455217
TI  - Tissue lipid lowering-effect of a traditional Nigerian anti-diabetic infusion of
      Rauwolfia vomitoria foilage and Citrus aurantium fruit.
AB  - The toxicity and anti-diabetic properties of an aqueous plant extract made by
      boiling Rauwolfia vomitoria foilage and Citrus aurantium fruits were evaluated in
      mice. A single dosage corresponding to 70x the human-daily-dose was non-toxic
      when administered to 6-week-old NMRI lean mice or 6- or 11-week-old C57BL/6J lean
      mice. Daily treatment of 11-week-old C57BL/KsBom-db (db/db) genetic diabetic mice
      with a dose corresponding to 10x human-daily-dose for 6 weeks facilitated a
      significant weight loss as compared to the untreated controls. During treatment,
      the db/db mice were maintained on the carbohydrate-deficient Altromin C1009 diet.
      Although the food intake in the treated mice was not statistically significant
      from that in the controls, the treated animals had significantly higher serum
      triglyceride contents, suggesting that the treatment induced lipid mobilization
      from internal stores. Moreover, the fatty acid profile of the eyes from the
      treated animals showed a significant reduction in total fatty acid content
      accompanied by a 33% reduction in estimated Stearoyl-CoA desaturase activity (p =
      0.039) as compared with controls. The fatty acid mobilization and a protection of
      the brittle C57BL/KsBom-db pancreas were observed 5 weeks after cessation of
      treatment when the treated animals were maintained on the poorer Altromin C1009
      diet.

PMID- 16455216
TI  - Puerariae radix promotes differentiation and mineralization in human osteoblast
      like SaOS-2 cells.
AB  - Puerariae radix (PR) is a traditional medicine herb used for enhancing body
      resistance against various diseases. The aim of this study was to identify
      whether Puerariae radix extract induces osteogenic activity in human osteoblast
      like SaOS-2 cells. Puerariae radix had no effect on the viability of osteoblastic
      cells, and dose-dependently increased alkaline phosphatase (ALP) activity.
      Puerariae radix markedly increased mRNA expression for vascular endothelial
      growth factor (VEGF), osteocalcin (OCN), osteopontin (OPN), and type I collagen
      (Col I) in SaOS-2 cells. Extracellular accumulation of proteins such as VEGF and
      Col I was increased in a dose-dependent manner. Also, Puerariae radix
      significantly induced mineralization in the culture of SaOS-2 cells. In
      conclusion, this study showed that Puerariae radix had no effect on viability,
      but enhanced ALP activity, VEGF, bone matrix proteins such as OCN, OPN, and Col
      I, and mineralization in SaOS-2 cells. These results propose that Puerariae radix
      can play an important role in osteoblastic bone formation, and may possibly lead
      to the development of bone-forming drugs.

PMID- 16455218
TI  - Identification of 5-hydroxy-tryptamine (bufotenine) in takini
      (Brosimumacutifolium Huber subsp. acutifolium C.C. Berg, Moraceae), a shamanic
      potion used in the Guiana Plateau.
AB  - This paper is the first thorough analysis of takini, a hallucinogen used by the
      shamans of several peoples in Suriname, French Guiana, and the region east of the
      Para in Brazil. The drug is contained in the latex of the Brosimum acutifolium
      tree, and until now, its psychotropic properties appeared inconsistent with the
      more general medicinal uses of the tree in the surrounding region. Our chemical
      and botanical studies reveal that the active ingredient of takini is bufotenine;
      and that this compound is only contained in the subspecies Brosimum acutifolium
      Huber subsp. acutifolium C.C. Berg that is found in the same area of the eastern
      Guianas.

PMID- 16455219
TI  - Y chromosome STR haplotypes in the Caribbean city of Cartagena (Colombia).
AB  - Haplotype data were obtained from a sample of 173 unrelated male individuals from
      Cartagena (Colombia), for 16 Y-chromosome STRs (DYS19, DYS385, DYS389 I, DYS389
      II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS460, DYS461,
      DYS635, GATA H4 and GATA A10). No shared haplotypes were observed, demonstrating
      the usefulness and informative power of these Y-STRs in male lineage
      identification in Cartagena. Genetic distances were calculated using previously
      published haplotype data and the lowest values were found for the comparisons
      with samples of Iberian origin.

PMID- 16455220
TI  - Syntrophomonas erecta subsp. sporosyntropha subsp. nov., a spore-forming
      bacterium that degrades short chain fatty acids in co-culture with methanogens.
AB  - Two obligate anaerobic bacterial strains (5-3-Z(T) and Y4-1) were isolated from
      river sediment and rice field mud, respectively. They degraded straight-chain
      fatty acids with 4-8 carbon atoms in syntrophic association with methanogens,
      however, neither tested branch-chain fatty acids nor could benzoate be degraded.
      The strains formed spores when cocultured with methanogens on butyrate, or when
      grew on butyrate plus dimethyl sulfoxide (DMSO) in pure culture. The cells were
      slightly curved rods with Gram-negative cell wall structure, and contained small
      amount of poly beta-hydroxyalkanoate. The strains could not degrade butyrate
      alone, nor could use fumarate, sulfate, thiosulfate, sulfur or nitrate as
      electron acceptors except DMSO for butyrate degradation. The generation time of
      strain 5-3-Z(T) was about 12h when growing on crotonate at 37 degrees C. The
      growth of the new strains occurred in the range of pH 5.5-8.4, and of temperature
      20-48 degrees C, and at NaCl concentration of 0-700 mM. The G+C content of the
      genomic DNA of strain 5-3-Z(T) was 40.6mol%. Phylogenetic analysis based on 16S
      rRNA gene similarity showed the two strains to be a member of species
      Syntrophomonas erecta (98.4-98.9% sequence similarity), however they differed
      from the existing strains in both phenotypic and genetic characteristics.
      Therefore, a new subspecies of S. erecta, S. erecta subsp. sporosyntropha was
      proposed. The type strain was 5-3-Z(T) (=CGMCC1.5032(T)=JCM13344(T)).

PMID- 16455221
TI  - Practitioner empathy, patient enablement and health outcomes: a prospective study
      of acupuncture patients.
AB  - OBJECTIVE: To measure acupuncture patients' perceptions of practitioner empathy
      at the initial consultation and its relationship with patient enablement, and
      prospectively reported changes in symptoms. METHODS: Fifteen acupuncturists asked
      consecutive new patients to complete a questionnaire within 2 days of the first
      consultation. The questionnaire included the Consultation and Relational Empathy
      (CARE) measure (a consultation process measure), the Patient Enablement
      Instrument (PEI, a consultation outcome measure) and the Measure Yourself Medical
      Outcome Profile (MYMOP), a patient-centred symptom, well-being and activity
      outcome measure. A postal follow-up questionnaire was completed at 8 weeks, which
      repeated these measures. RESULTS: Fifty-two patients (58% of all new patients)
      completed the initial questionnaire. Of these, 41 (79%) completed the follow-up
      questionnaire. From a multiple regression analysis, which controlled for known
      confounders, empathy was found to be associated with enablement at the initial
      consultation (Beta coefficient=0.16, 95% CI: 0.02-0.31, p=0.03) and empathy
      predicted changes in health outcome (MYMOP) at 8 weeks (Beta=0.07, 95% CI: 0.004
      0.13, p=0.04). CONCLUSION: Patients' perception of practitioner empathy was
      associated with patient enablement at initial consultation and predicted changes
      in health outcome at 8 weeks. PRACTICE IMPLICATIONS: The empathy of
      practitioners, as perceived by patients, has a direct impact on patient
      enablement and health outcome.

PMID- 16455222
TI  - The effects of a lifestyle physical activity counseling program with feedback of
      a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study.
AB  - OBJECTIVE: To study the effects of a lifestyle physical activity counseling
      program with feedback of a pedometer during pulmonary rehabilitation. METHODS:
      Twenty-one chronic obstructive pulmonary disease (COPD) patients were randomized
      to an experimental group that followed a regular rehabilitation program plus the
      counseling intervention or to a control group that only followed rehabilitation.
      The primary outcome was daily physical activity assessed by pedometers. Secondary
      outcomes were physical fitness, health-related quality of life, activities of
      daily living, depression and self-efficacy. RESULTS: The experimental group
      showed an increase of 1,430 steps/day (+69% from baseline), whereas the control
      group showed an increase of 455 steps/day (+19%) (p = 0.11 for group x time
      interaction). The secondary outcomes showed no differences. CONCLUSION AND
      PRACTICE IMPLICATIONS: This study showed that the use of the pedometer, in
      combination with exercise counseling and the stimulation of lifestyle physical
      activity, is a feasible addition to pulmonary rehabilitation which may improve
      outcome and maintenance of rehabilitation results.

PMID- 16455224
TI  - Ablation of advanced tongue or base of tongue cancer and reconstruction with free
      flap: functional outcomes.
AB  - AIM: To evaluate the functional outcomes of patients who underwent total or
      nearly total glossectomy for advanced tongue or base of tongue cancer. MATERIAL
      AND METHODS: We used the radial forearm free flap (RFFF), anterior lateral thigh
      flap (ALTF) or fibular osteocutaneous flap (FOCF) to reconstruct the oral defect
      after radical resection in 39 patients undergoing total or nearly total
      glossectomy with laryngeal preservation. RESULTS: Good functional outcomes,
      measured by independent feeding, speech and swallowing were achieved in 35, 36
      and 35 patients, respectively. The cumulative 4-year survival rates were 63.8%
      for tongue cancer and 42.9% for base of tongue cancer. CONCLUSION: Reconstruction
      with free flaps is a feasible method to restore the functional outcomes in speech
      and deglutition among patients who undergo total or nearly total glossectomy with
      laryngeal preservation.

PMID- 16455223
TI  - Adenohypophyseal function in bitches treated with medroxyprogesterone acetate.
AB  - The aim of this study was to investigate the effects of treatment with
      medroxyprogesterone acetate (MPA) on canine adenohypophyseal function. Five
      Beagle bitches were treated with MPA (10mg/kg, every 4 weeks) and their
      adenohypophyseal function was assessed in a combined adenohypophyseal function
      test. Four hypophysiotropic hormones (CRH, GHRH, GnRH, and TRH) were administered
      before and 2, 5, 8, and 11 months after the start of MPA treatment, and blood
      samples for determination of the plasma concentrations of ACTH, cortisol, GH, IGF
      1, LH, FSH, prolactin, alpha-MSH, and TSH were collected at -15, 0, 5, 10, 20,
      30, and 45 min after suprapituitary stimulation. MPA successfully prevented the
      occurrence of estrus, ovulation, and a subsequent luteal phase. MPA treatment did
      not affect basal and GnRH-induced plasma LH concentrations. The basal plasma FSH
      concentration was significantly higher at 2 months after the start of MPA
      treatment than before or at 5, 8, and 11 months after the start of treatment. The
      maximal FSH increment and the AUC for FSH after suprapituitary stimulation were
      significantly higher before treatment than at 5, 8, and 11 months of MPA
      treatment. Differences in mean basal plasma GH concentrations before and during
      treatment were not significant, but MPA treatment resulted in significantly
      elevated basal plasma IGF-1 concentrations at 8 and 11 months. MPA treatment did
      not affect basal and stimulated plasma ACTH concentrations, with the exception of
      a decreased AUC for ACTH at 11 months. In contrast, the maximal cortisol
      increment and the AUC for cortisol after suprapituitary stimulation were
      significantly lower during MPA treatment than prior to treatment. MPA treatment
      did not affect basal plasma concentrations of prolactin, TSH, and alpha-MSH, with
      the exception of slightly increased basal plasma TSH concentrations at 8 months
      of treatment. MPA treatment did not affect TRH-induced plasma concentrations of
      prolactin and TSH. In conclusion, the effects of chronic MPA treatment on
      adenohypophyseal function included increased FSH secretion, unaffected LH
      secretion, activation of the mammary GH-induced IGF-I secretion, slightly
      activated TSH secretion, suppression of the hypothalamic-pituitary-adrenocortical
      axis, and unaffected secretion of prolactin and alpha-MSH.

PMID- 16455225
TI  - [Inhalation induction with sevoflurane in paediatrics: what is new?].
AB  - The delay for loss of consciousness can be shortened by using high concentration
      sevoflurane > 6% and by adding N2O during inhalation induction with sevoflurane
      in paediatrics. Mean time for tracheal tube insertion is lower than 5 min in the
      majority of studies. This shorter delay is not associated with any significant
      increase in clinical side effects. However, recent studies have demonstrated the
      epileptogenic effect of high effect site sevoflurane concentration (occurrence of
      spike wave on the EEG). Inhalation induction with high alveolar sevoflurane
      concentration is questionable mainly when it is associated with hyperventilation.
      Positive pressure ventilation or pressure support ventilation make it possible to
      maintain normocapnia and to monitor FeSevo. Adding a narcotic decreases the
      target cerebral concentration required to perform tracheal intubation and
      consequently the risk of spike wave occurrence.

PMID- 16455226
TI  - [Regional organization for intensive care in children, need for maintenance of
      competence in paediatric anaesthesia and intensive care].
AB  - The recent French text concerning the medical care both of the child and the
      teenager classifies the establishments either in specialized centers or in
      proximity centers according to their level in the management of children and
      teenagers, the competences of their medical teams, their organization in
      permanence of care and the volume of acts they carry out and pathologies they
      treat by class of age. This grid of the paediatric activities implies a new
      organization both in paediatric surgery and in paediatric ENT and consequently in
      the anaesthetic organization. Anaesthetic competences necessary to the
      achievement of this mission and the means of maintaining these later are analyzed
      and compared with some foreign experiments.

PMID- 16455228
TI  - [Surgical management of paediatric malignant bone tumours].
AB  - The malignant bone tumours in children are rare, concerning 5% of the all
      paediatric tumours. Among all paediatric bone tumours, 15% of them are malignant.
      The main bone tumours in children are the osteosarcoma and the Ewing sarcoma. The
      diagnosis and treatment need a multidisciplinary medical team. It is essential in
      front of potential clinical or radiological signs, to perform quickly the
      specific medical exams and biopsy. The treatment needs a paediatric medical and
      surgical staff.

PMID- 16455227
TI  - [Local anaesthetics: what can the pure S enantiomers contribute?].
AB  - The use of levobupivacaine and of ropivacaine may increase the safety of regional
      anaesthesia. These pure enantiomers have similar pharmacokinetic properties as
      those of the racemic mixtures. However, they are less cardiotoxic than the
      racemic mixtures, especially at the high heart rate usually encountered in
      infants. We may then recommend the use of these agents in the paediatric
      patients.

PMID- 16455229
TI  - Chondroitin sulfate B and heparin mediate adhesion of Penicillium marneffei
      conidia to host extracellular matrices.
AB  - Penicilliosis is a disseminated infection in immunocompromised individuals caused
      by the dimorphic fungus, Penicillium marneffei. Very little is known about its
      route of infection, however, it is thought that initial infection occurs through
      inhalation of conidia. We investigated the role played by various extracellular
      matrix glycosaminoglycans (GAGs) in the initial adherence of P. marneffei conidia
      using a direct adhesion assay. GAGs were further used to block the binding of
      fungal spores to human lung epithelial cells and highly sulfated GAGs were tested
      for their inhibitory effects owing to their degree of sulfation. Our results
      demonstrated high levels of conidial adhesion to chondroitin sulfate B, heparin
      and highly sulfated chitosan (CP-3). No direct adherence was observed to
      immobilized chondroitin sulfate (CS) A, CSC, CSD and hyaluronic acid, as well as
      chitosans with low sulfate content. The results suggested that P. marneffei
      conidia bind to iduronic acid (IdoA) of the polysaccharide chains. Involvement of
      negatively charged sulfate groups in adhesion was also indicated. Furthermore,
      significant inhibition of conidial adherence to A549 cells was observed in the
      presence of CSB, heparan sulfate (HS), heparin and CP-3. It was further
      demonstrated that GAGs can affect the adhesion of conidia to fibronectin and
      laminin, glycoproteins that have previously been implicated as adhesive receptors
      for fungal conidia. CSB and HS could partially inhibit the adhesion of fungal
      conidia to laminin and fibronectin implying that conidia can weakly interact with
      the IdoA GAG-binding domain(s) of these molecules. The data indicated that, in
      addition to fibronectin and laminin, IdoA-containing GAGs may play an important
      role in fungal adherence to the surface of human lung epithelium.

PMID- 16455230
TI  - Assessment of the human epidermis model SkinEthic RHE for in vitro skin corrosion
      testing of chemicals according to new OECD TG 431.
AB  - Based on two successfully completed ECVAM validation studies for in vitro skin
      corrosion testing of chemicals, the National Co-ordinators of OECD Test Guideline
      Programme endorsed in 2002 two new test guidelines: TG 430 'Transcutaneous
      Electrical Resistance assay' and TG 431 'Human Skin Model Test'. To allow all
      suitable in vitro human reconstructed (dermal or epidermal) models to be used for
      skin corrosion testing, the OECD TG 431 defines general and functional conditions
      that the model must meet before it will be routinely used for skin corrosion
      testing. In addition, the guideline requires correct prediction of 12 reference
      chemicals and assessment of intra- and inter-laboratory variability. To show that
      the OECD TG 431 concept works, in 2003 ZEBET tested several chemicals from the
      ECVAM validation trials on the SkinEthic reconstituted human epidermal (RHE)
      model. Based on knowledge that reconstructed human skin models perform similarly
      in toxicological studies, it was decided to adopt the validated EpiDerm skin
      corrosion test protocol and prediction model to the SkinEthic model. After minor
      technical changes, classifications were obtained in concordance with those
      reported for the validated human skin models EPISKIN and EpiDerm. To allow
      adequate determination of inter-laboratory reproducibility, a blind trial was
      conducted in three laboratories -- ZEBET (D), Safepharm (UK) and BASF (D), in
      which the 12 endorsed reference chemicals were tested. Results obtained with the
      SkinEthic epidermal model were reproducible, both within and between
      laboratories, and over time. Concordance between the in vitro predictions of skin
      corrosivity potential obtained with the SkinEthic model and the predictions
      obtained with the accepted tests of OECD TG 430 and TG 431 was very good. The new
      test was able to distinguish between corrosive and non-corrosive reference
      chemicals with an accuracy of 93%.

PMID- 16455231
TI  - Expression profiling of uniparental mouse embryos is inefficient in identifying
      novel imprinted genes.
AB  - Imprinted genes are expressed from only one allele in a parent-of-origin-specific
      manner. We here describe a systematic approach to identify novel imprinted genes
      using quantification of allele-specific expression by Pyrosequencing, a highly
      accurate method to detect allele-specific expression differences. Sixty-eight
      candidate imprinted transcripts mapping to known imprinted chromosomal regions
      were selected from a recent expression profiling study of uniparental mouse
      embryos and analyzed. Three novel imprinted transcripts encoding putative non
      protein-coding RNAs were identified on the basis of parent-of-origin-specific
      monoallelic expression in E11.5 (C57BL/6 x Cast/Ei)F1 and informative (C57BL/6 x
      Cast/Ei) x C57BL/6 backcross embryos. In addition, four transcripts with
      preferential expression of a strain-specific allele were found. Intriguingly, a
      vast majority of the analyzed transcripts showed no imprinting-associated
      expression in F1 embryos. These data strengthen the view that a large fraction of
      nonimprinted genes is differentially expressed between parthenogenetic and
      androgenetic embryos and question the efficiency of expression profiling of
      uniparental embryos to identify novel imprinted genes.

PMID- 16455232
TI  - A novel missense mutation in the mouse hairless gene causes irreversible hair
      loss: genetic and molecular analyses of Hr m1Enu.
AB  - A novel autosomal recessive mutant was produced using N-ethyl-N-nitrosourea
      mutagenesis. The characteristics of the mutant mice included progressive
      irreversible hair loss within a month of birth, wrinkled skin, and long curved
      nails. Linkage analysis revealed that the causative gene is linked to D14Mit193
      on chromosome 14. Sequence analysis of the complete cDNA of the candidate gene,
      hairless (Hr), identified a homozygous G-to-T transition at nucleotide 3572,
      leading to the substitution of glycine by tryptophan, designated Gly960Trp. This
      missense mutation occurs in the vicinity of repression domain 3 of the hairless
      protein (HR). This allele was named Hr(m1Enu). The relative amounts of Hr mRNA
      and HR protein determined by real-time PCR and Western blot analyses,
      respectively, were slightly elevated in the mutant mice. Quantitative real-time
      PCR analysis revealed the increased expression of Kc1 and Vdr in the mutant mice,
      whereas the expression of Nrs1 and Krtap16-6 was decreased. These results suggest
      that the Gly960Trp substitution in HR protein in Hr(m1Enu) mice may alter the
      function of HR as a transcriptional corepressor.

PMID- 16455233
TI  - Class 2 integron-associated antibiotic resistance in Shigella sonnei isolates in
      Dakar, Senegal.
AB  - Forty-three Shigella sonnei isolates from adult patients with diarrhoea in Dakar
      were analysed for the presence of integrons. Isolates were resistant to
      sulphamethoxazole, trimethoprim, tetracycline, streptomycin and spectinomycin. A
      high prevalence of class 2 integrons (93%) was found. These integrons showed
      three distinct structures: a class 2 integron, part of the Tn7 family and its
      derivatives, carrying four cassettes in the order dfrA1-sat-aadA1-orfX; a
      truncated class 2 integron, without orfX; and a third type ca. 4 kb in size.
      These class 2 integrons probably play a role in the spread of multiresistance in
      S. sonnei isolates. To our knowledge, this is the first description of class 2
      integrons in S. sonnei isolated in sub-Saharan Africa.

PMID- 16455234
TI  - Griseofulvin and ketoconazole solubilization by bile salts studied using
      fluorescence spectroscopy.
AB  - The capacity of solubilization of the five physiological bile salts: cholate,
      deoxicholate, hiocholate, quenodeoxicholate and taurocholate were assayed on two
      low aqueous soluble antimicotic agents: griseofulvin and ketoconazole. The
      fluorescence emission of these antimicotic agents was used as tool to study their
      solubilization in bile salts micelle. Griseofulvin enhanced its fluorescence and
      shifted to the blue in the presence of bile salts micelles. The shift was
      dependent of the polarizability of the micelle zone where the antimicotic is
      located. Cholate and deoxicholate showed a good solubilization capacity for
      griseofulvin: 321 mol and 394 mol surfactant per mol of antimicotic,
      respectively. These values decreased in the presence of NaCl in agreement with a
      compactness of the micelle due to an electrostatic repulsion decreasing between
      the bile salts monomer negatively charged. The imidazole and piperazine rings
      present in the ketoconazole molecule give to this the capacity of fluorescence
      emission with two vibronic bands at 364 nm and 382 nm, respectively. The
      solubilization in cholate micelle induced an increase in the band at 382 nm,
      while deoxicholate induced the opposite effect, suggesting a strong intercation
      between the polar groups of ketoconazole molecule (imidazole and piperazine
      rings) and the (-)OH of these bile salts. The solubilization capacities were 47
      mol and 117 mol surfactant per ketoconazole mol for cholate and deoxicholate,
      respectively. The other bile salts assayed did not show any appreciable
      solubilization capacity. Ketoconazole and griseofulvin solubilized in micelles of
      cholate and deoxicholate were stable during the thermal recycling treatment for
      over 100 days.

PMID- 16455235
TI  - Evaluation of 5-aminosalicyltaurine as a colon-specific prodrug of 5
      aminosalicylic acid for treatment of experimental colitis.
AB  - We previously reported that 5-aminosalicyltaurine (taurine-conjugated 5-ASA, 5
      ASA-Tau) showed a potential as a colon-specific prodrug of 5-aminosalicylic acid
      (5-ASA) by in vitro evaluation. In this report, we in vivo-evaluated 5-ASA-Tau as
      a colon-specific prodrug for treatment of experimental colitis. Taurine
      conjugation of 5-ASA greatly reduced absorption of 5-ASA from the intestine. Oral
      administration of taurine-conjugated 5-ASA not only increased the colonic
      delivery efficiency of 5-ASA but also decreased the systemic absorption of free 5
      ASA as compared with that of 5-ASA and, moreover, taurine is similarly effective
      to known colon-specific carriers for 5-ASA, glycine and aspartic acid, suggesting
      that taurine conjugation is an efficient way to increase the therapeutic effect
      and to reduce the adverse effects of 5-ASA. Intracolonic treatment with combined
      5-ASA/taurine additively ameliorated TNBS-induced colitis rats indicating that
      taurine acted as not only a promoiety but also a therapeutically active agent.
      Furthermore, 5-ASA-Tau is slightly more effective than sulfasalazine in
      alleviating the colonic inflammation induced by TNBS. Taken together, our data
      suggest that 5-ASA-Tau is a potential colon-specific prodrug of 5-aminosalicylic
      acid with improved therapeutic activity against inflammatory bowel disease.

PMID- 16455236
TI  - Gliotransmission at central glutamatergic synapses: D-serine on stage.
AB  - Long ignored and only considered as housekeeping cells for neurons, astroglial
      cells in the last decade have gained increasing attention as key players of
      higher functions in healthy brain, but also in diseases. This revolution in our
      way to think the active brain culminates in the concept of a tripartite synapse,
      which considers glial cells and notably astrocytes as an integral dynamic partner
      of synapses. Glia not only listens but also talks to neurons through the release
      of neuroactive substances. Recently much attention has been paid to the role
      played by the atypical amino acid D-serine in this signalling pathway. This
      molecule synthesized through racemization of L-serine fulfils most criteria as a
      gliotransmitter and as the endogenous ligand for the strychnine-insensitive
      glycine binding site of the NMDA receptors. D-serine is considered to be a
      permissive factor for long-term changes in synaptic plasticity and neuronal
      migration through activation of NMDA receptors. It is also known that disturbance
      of NMDA receptors activity can cause cell death. Not surprisingly, then, D-serine
      has also been found to promote neurons death in experimental models of beta
      amyloid peptide-induced neuroinflammation and of ischaemia by overactivating the
      NMDA receptors. Finally, in a more recent past, studies have pointed to the
      molecular mechanisms leading to D-serine release into and removal from the
      synaptic cleft.

PMID- 16455237
TI  - Role of PTHrp and PTHrp-engaged pathways in MCF-7 cells migration/invasion.
AB  - In this paper the effect of N-terminal parathyroid hormone-related protein
      (PTHrp) and PTHrp-engaged pathways on MCF-7 breast cancer cell
      migration/invasivity and matrix metalloproteinases (MMPs) production were
      investigated. We found that: a) migration is not affected by PTHrp and Forskolin
      (FK)-activated PKA, while Phorbol Myristate Acetate (PMA)-activated PKC strongly
      stimulates MCF-7 cells motility. b) MMPs production was unaffected by PTHrp, but
      FK reduced membrane-type (MT)-1 MMP expression. Conversely, PMA induced a marked
      increase of MT1-MMP and MMP-9. c) Chemical activation of PKC is not sufficient,
      by itself, to confer invasive ability to MCF-7 cells, unless they were provided
      with additional factors, supplied by fibroblasts. d) Matrix invasion likely
      occurs through an activation cascade, involving at least three components: pro
      MMP-9 and MT-1 MMP (supplied by PMA-stimulated MCF-7 cells) and pro MMP-2
      (supplied by fibroblasts). e) The selective chemical inhibition of the
      adenylylciclase (AC)/PKA and phospholipase C (PLC)/PKC pathways confirmed that
      MCF-7 cells invasivity is not affected by exogenous PTHrp, which can only
      modulate their growth. However, the PTHrp responsibility in breast cancer
      invasion cannot be completely excluded. Indeed, fibroblasts are known to respond
      to PTHrp (which is a normal product of MCF-7 as well as other breast cancer
      cells) with enhanced release of MMP-2. On the basis of the documented requirement
      of fibroblast-derived MMP-2 for MCF-7 cell invasivity, a novel humoral fibroblast
      breast cancer cell interaction, mediated by PTHrp, can be recognised.

PMID- 16455238
TI  - Cytometry on a chip: cellular phenotypic and functional analysis using grating
      coupled surface plasmon resonance.
AB  - Grating-coupled surface plasmon resonance imaging (GCSPRI) is a method for the
      accurate assessment of both cell phenotype and function. In GCSPRI, cells and/or
      proteins of interest are flowed across antibodies immobilized on a gold-coated
      sensor chip. The surface of the chip is illuminated with monochromatic light that
      couples with surface plasmons in the gold. At a specific angle of incidence, the
      GCSPR angle, the maximum amount of coupling occurs. Shifts in the GCSPR angle can
      be correlated with refractive index changes following cell or analyte capture by
      the immobilized antibodies. In addition, GCSPRI can image the cells as they are
      being captured. GCSPRI's multiplexed format allows for the parallel assessment of
      up to 400 individual antibody regions. In this paper, we demonstrate GCSPRI's
      ability to identify cells and proteins of interest and compare results to a
      traditional flow cytometry system. This technology represents a fast and powerful
      method for the simultaneous assessment of cell phenotype and function.

PMID- 16455239
TI  - An irresistible thirst for knowledge!

PMID- 16455240
TI  - Biodiesel production using anionic ion-exchange resin as heterogeneous catalyst.
AB  - The transesterification reactions of triolein with ethanol using various ion
      exchange resin catalysts were conducted to produce ethyl oleate as a biodiesel.
      The anion-exchange resins exhibited much higher catalytic activities than the
      cation-exchange resin. The anion-exchange resin with a lower cross-linking
      density and a smaller particle size gave a high reaction rate as well as a high
      conversion. By combining the three-step regeneration method, the resin could be
      repeatedly used for the batch transesterification without any loss in the
      catalytic activity. A continuous transesterification reaction was carried out
      using an expanded bed reactor packed with the most active resin. The reactor
      system permitted the continuous production of ethyl oleate with a high
      conversion.

PMID- 16455241
TI  - Design, synthesis, and biological evaluation of a scaffold for iGluR ligands
      based on the structure of (-)-dysiherbaine.
AB  - The design and synthesis of four 2,2-disubstituted dihydrobenzofurans that are
      structurally related to several glutamate-containing natural products, including
      (-)-dysiherbaine, is described. Biological evaluation of these analogs shows that
      one is a KA receptor antagonist and another is an NMDA receptor agonist.

PMID- 16455242
TI  - Semisynthesis of C-ring modified triptolide analogues and their cytotoxic
      activities.
AB  - Several C-ring modified analogues of a potent antileukemic diterpene, triptolide
      (1), were synthesized and their structure-activity relationships were studied.

PMID- 16455243
TI  - The catecholic antioxidant piceatannol is an effective nitrosation inhibitor via
      an unusual double bond nitration.
AB  - Piceatannol (1) was found to be more effective than caffeic acid, an established
      antinitrosating agent, in inhibiting N-nitrosation of 2,3-diaminonaphthalene.
      Product analysis of the reaction mixture of 1 (20 microM) with nitrite ions (80
      microM) at pH 3.0 and at 37 degrees C showed conversion to a single major
      nitration product, (E)-3,3',4,5'-tetrahydroxy-beta-nitrostilbene (2) (68% yield).
      This would result from an unexpected nitration at the double bond sector via the
      4-phenoxyl radical, which was analyzed at the unrestricted DFT level.

PMID- 16455244
TI  - Synthesis of constrained ceramide analogs and their potent antileukemic
      activities.
AB  - Constrained ceramide analogs were designed and synthesized by binding terminal
      alcohol and amine of ceramide with additional carbonyl functional group as 3
      acetyl (3), 3-propionyl (4), 3-benzoyl (5), and 3-hexadecanoyl-4-(1
      hydroxyhexadec-2-enyl)-oxazolidin-2-ones (6). Compounds 4 and 5 showed potent
      antileukemic activities against human leukemia HL-60 cells with good correlation
      between cell death and DNA fragmentation.

PMID- 16455245
TI  - Novel skeleton terpenes from Celastrus hypoleucus with anti-tumor activities.
AB  - Celahypodiol 1, an unusual 17-membered carbon diterpenoid with a novel skeleton,
      and a new triterpenoid 12-oleanene-3beta,6alpha-diol 2, together with four known
      compounds furreginol 3, suigol 4, 20(30)-lupene-3beta, 29-diol 5, and 20(29)
      lupene-1beta,3beta-diol 6, were isolated from the stalks of Celastrus hypoleucus
      (Oliv.) Warb. Their structures were established by means of spectroscopic
      analysis, including 2D NMR. The new compounds exhibited anti-tumor activities
      against a panel of human tumor cell lines.

PMID- 16455246
TI  - Stereoselective synthesis and fungicidal activities of (E)-alpha-(methoxyimino)
      benzeneacetate derivatives containing 1,3,4-oxadiazole ring.
AB  - Fifteen novel (E)-alpha-(methoxyimino)-benzeneacetate derivatives, the analogues
      of strobilurins, which contain two pharmacophoric substructures of (E)-methyl
      methoxyiminoacetate moiety and 1,3,4-oxadiazole ring were stereoselectively
      synthesized. It was first found that the coupling reaction could give
      stereoselectively the key intermediate (E) and (Z)-methyl 2-(hydroxyimino)-2-o
      tolylacetate 2 with a ratio of 14:1. The preliminary bioassays indicated that all
      the compounds 1 showed potent fungicidal activity against Rhizoctonia solani,
      Botrytis cinereapers, Gibberella zeae, Physalospora piricola and Bipolaris
      mayclis, and all of the tested compounds 1a-1o had more potent fungicidal
      activities against R. solani than Kresoxim-methyl.

PMID- 16455247
TI  - Pyridone derivatives as potent and selective VLA-4 integrin antagonists.
AB  - A novel series of pyridone inhibitors has been identified through pharmacophore
      analysis, as potent antagonists of VLA-4.

PMID- 16455248
TI  - The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and
      potential Alzheimer's disease modifying agent.
AB  - The subtle modification of a selection of Abeta42 inhibiting non-steroidal anti
      inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues,
      was anticipated to ablate their cyclooxygenase activity whilst maintaining
      Abeta42 inhibition. Methylflurbiprofen 6 exhibited similar in vitro Abeta42
      inhibition to its parent NSAID Flurbiprofen and was further evaluated in the
      Tg2576 mouse model of Alzheimer's disease and an animal model of gastro
      intestinal (GI) impairment, but proved unviable for further clinical development.

PMID- 16455249
TI  - New ligand-based approach for the discovery of antitrypanosomal compounds.
AB  - The antitrypanosomal activity of 10 already synthesized compounds was in silico
      predicted as well as in vitro and in vivo explored against Trypanosoma cruzi. For
      the computational study, an approach based on non-stochastic linear fingerprints
      to the identification of potential antichagasic compounds is introduced.
      Molecular structures of 66 organic compounds, 28 with antitrypanosomal activity
      and 38 having other clinical uses, were parameterized by means of the TOMOCOMD
      CARDD software. A linear classification function was derived allowing the
      discrimination between active and inactive compounds with a confidence of 95%. As
      predicted, seven compounds showed antitrypanosomal activity (%AE>70) against
      epimastigotic forms of T. cruzi at a concentration of 100mug/mL. After an
      unspecific cytotoxic assay, three compounds were evaluated against amastigote
      forms of the parasite. An in vivo test was carried out for one of the studied
      compounds.

PMID- 16455250
TI  - Synthesis of carbon-11 and fluorine-18 labeled N-acetyl-1-aryl-6,7-dimethoxy
      1,2,3,4-tetrahydroisoquinoline derivatives as new potential PET AMPA receptor
      ligands.
AB  - New carbon-11 and fluorine-18 labeled N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline derivatives were designed and synthesized as potential
      positron emission tomography AMPA (2-amino-3-(3-hydroxy-5-methylisoxazol-4
      yl)propionic acid) receptor ligands to image brain diseases. The single crystal
      structure of the most potent compound N-acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy
      1,2,3,4-tetrahydroisoquinoline (5a) is first reported.

PMID- 16455251
TI  - Factor VIIa inhibitors: improved pharmacokinetic parameters.
AB  - Efforts to improve the potency and pharmacokinetic properties of small molecule
      factor VIIa inhibitors are described. Small structural modifications to existing
      leads allow the modulation of half-life and clearance, potentially making these
      compounds suitable candidates for drug development.

PMID- 16455252
TI  - Benzimidazole inhibitors of hepatitis C virus NS5B polymerase: identification of
      2-[(4-diarylmethoxy)phenyl]-benzimidazole.
AB  - A series of 1-cycloalkyl-2-phenyl-1H-benzimidazole-5-carboxylic acid derivatives
      was synthesized and evaluated for inhibitory activity against HCV NS5B RNA
      dependent RNA polymerase (RdRp). A SAR study was performed and led to identify
      the 2-[(4-diarylmethoxy)phenyl]-benzimidazoles as potent inhibitors. They inhibit
      subgenomic HCV RNA replication in the replicon cells at low micromolar
      concentrations (EC(50) as low as 1.1microM). They are selective against DNA
      polymerases (IC(50)>10microM) and exhibit low cytotoxicity.

PMID- 16455253
TI  - An efficient, asymmetric solid-phase synthesis of benzothiadiazine-substituted
      tetramic acids: potent inhibitors of the hepatitis C virus RNA-dependent RNA
      polymerase.
AB  - An efficient, asymmetric solid-phase synthesis of benzothiadiazine-substituted
      tetramic acids is reported. Starting from commercially available chiral Fmoc
      protected alpha-amino acids loaded onto Wang resin, Fmoc removal, reductive
      amination followed by amide bond formation, and base-catalyzed cyclization with
      simultaneous cleavage from the resin provided the desired products. Compounds
      described are potent inhibitors of the hepatitis C virus RNA-dependent RNA
      polymerase.

PMID- 16455254
TI  - Evaluation of anti-inflammatory and antioxidant activities of mixed-ligand Cu(II)
      complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino
      2-thiazoline.
AB  - A new series of complexes of the type [Cu(dien)(2a-2tzn)Y2] and [Cu(dienXX)(2a
      2tzn)Y2] has been tested for anti-inflammatory and antioxidant activity. The
      tested compounds inhibit significantly the carrageenin induced paw edema (36.4
      55.8%) and present important scavenging activities. Although their interaction
      with the free stable radical DPPH is not high they peroxide anions. Compound 7 is
      the most potent (55.8%) in the in vivo experiment. Lipophilicity--as RM values
      and theoretically calculated logP values--has been determined. An attempt to
      correlate the biological results with their structural characteristics and
      physicochemical parameters has been done.

PMID- 16455255
TI  - 3D-QSAR studies of farnesyltransferase inhibitors: a comparative molecular field
      analysis approach.
AB  - 3D-QSAR analysis has been performed on a series of previously synthesized
      benzonitrile derivatives, which were screened as farnesyltransferase inhibitors,
      using comparative molecular field analysis (CoMFA) with partial least-square fit
      to predict the steric and electrostatic molecular field interactions for the
      activity. The CoMFA study was carried out using a training set of 34 compounds.
      The predictive ability of the model developed was assessed using a test set of
      eight compounds (r(pred)(2) as high as 0.770). The analyzed 3D-QSAR CoMFA model
      has demonstrated a good fit, having r(2) value of 0.991 and cross-validated
      coefficient q(2) value as 0.619. The analysis of CoMFA contour maps provided
      insight into the possible modification of the molecules for better activity.

PMID- 16455257
TI  - W. Grey Walter, pioneer in the electroencephalogram, robotics, cybernetics,
      artificial intelligence.
AB  - With the announcement by William Lennox at the 1935 London International
      Neurology Congress of the use of electroencephalography in the study of epilepsy,
      it became evident that a new and powerful technique for the investigation of
      seizures had been discovered. William Grey Walter, a young researcher finishing
      his post-graduate studies at Cambridge, was selected to construct and study the
      EEG in clinical neurology at the Maudsley Hospital, London. His hugely productive
      pioneering career in the use of EEG would eventually lead to groundbreaking work
      in other fields --the emerging sciences of robotics, cybernetics, and early work
      in artificial intelligence. In this historical note his pioneering work in the
      fields of clinical neurophysiology is documented, both in the areas of
      epileptology and tumour detection. His landmark contributions to clinical
      neurophysiology are worthy of documentation.

PMID- 16455256
TI  - Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory
      compounds.
AB  - A novel series of potent blockers of the monocarboxylate transporter, MCT1, is
      disclosed. From very potent but lipophilic lead compounds, systematic changes to
      all parts of the molecule, targeting reduction in log D, afforded compounds with
      significantly improved overall properties. These compounds show potent
      immunomodulatory activity.

PMID- 16455258
TI  - Synthesis and receptor binding affinity of carboxylate analogues of the mannose 6
      phosphate recognition marker.
AB  - The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) is
      involved in multiple physiological pathways including targeting of lysosomal
      enzymes, degradation of IGF2, and cicatrization through TGFbeta activation. To
      target potential therapeutics to this membrane receptor, four carboxylate
      analogues of mannose 6-phosphate (M6P) were synthesized. Three of them, two
      isosteric carboxylate analogues and a malonate derivative, showed a binding
      affinity for the M6P/IGF2R equivalent to or higher than that of M6P. Contrary to
      M6P, all these analogues were particularly stable in human serum. Moreover, these
      derivatives did not present any cytotoxic activity against two human cell lines.
      These analogues represent a new potential for the lysosomal targeting of enzyme
      replacement therapy in lysosomal diseases or to prevent the membrane-associated
      activities of the M6P/IGF2R.

PMID- 16455260
TI  - Effective discrimination of antimalarial potency of artemisinin compounds based
      on quantum chemical calculations of their reaction mechanism.
AB  - The reaction mechanism of 12 antimalarial artemisinin compounds with two
      competitive pathways was studied by means of quantum chemical calculations using
      the IMOMO(B3LYP/6-31(d,p):HF/3-21G) method. The oxygen-centered radicals, carbon
      centered radicals, and transition states (TS) in both pathways were geometrically
      optimized. The obtained kinetic and thermodynamic energy profiles show that
      homolytic C-C cleavage reaction (pathway 2) is energetically more preferable than
      an intramolecular 1,5-hydrogen shift process (pathway 1), which is consistent
      with the docking calculations. However, compounds that can easily proceed along
      the pathway 1 have high activity. Therefore, both pathways are important for
      antimalarial activity. Moreover, effective discrimination between high and low
      activity compounds using EA1, deltaE1, and deltaE(1A-2A) was accomplished.

PMID- 16455259
TI  - Synthesis and radiosynthesis of [(18)F]FPhEP, a novel alpha(4)beta(2)-selective,
      epibatidine-based antagonist for PET imaging of nicotinic acetylcholine
      receptors.
AB  - FPhEP (1, (+/-)-2-exo-(2'-fluoro-3'-phenyl-pyridin-5'-yl)-7
      azabicyclo[2.2.1]heptane) belongs to a recently described novel series of 3'
      phenyl analogues of epibatidine, which not only possess subnanomolar affinity and
      high selectivity for brain alpha4beta2 neuronal nicotinic acetylcholine receptors
      (nAChRs), but also were reported as functional antagonists of low toxicity (up to
      15 mg/kg in mice). FPhEP (1, K(i) of 0.24 nM against [(3)H]epibatidine) as
      reference as well as the corresponding N-Boc-protected chloro- and bromo
      derivatives (3a,b) as precursors for labelling with fluorine-18 were synthesized
      in eight and nine steps, respectively, from commercially available N-Boc-pyrrole
      (overall yields=17% for 1, 9% for 3a and 8% for 3b). FPhEP (1) was labelled with
      fluorine-18 using the following two-step radiochemical process: (1) no-carrier
      added nucleophilic heteroaromatic ortho-radiofluorination from the corresponding
      N-Boc-protected chloro- or bromo derivatives (3 a,b-1mg) and the activated
      K[(18)F]F-Kryptofix(222) complex in DMSO using microwave activation at 250 W for
      1.5 min, followed by (2) quantitative TFA-induced removal of the N-Boc-protective
      group. Radiochemically pure (>99%) [(18)F]FPhEP ([(18)F]-1, 2.22-3.33 GBq, 66-137
      GBq/micromol) was obtained after semi-preparative HPLC (Symmetry C18, eluent aq
      0.05 M NaH(2)PO(4)/CH(3)CN, 80:20 (v:v)) in 75-80 min starting from a 18.5 GBq
      aliquot of a cyclotron-produced [(18)F]fluoride production batch (10-20% nondecay
      corrected overall yield). In vitro binding studies on rat whole-brain membranes
      demonstrated a subnanomolar affinity (K(D) 660 pM) of [(18)F]FPhEP ([(18)F]-1)
      for nAChRs. In vitro autoradiographic studies also showed a good contrast between
      nAChR-rich and -poor regions with a low non-specific binding. Comparison of in
      vivo Positron Emission Tomography (PET) kinetics of [(18)F]FPhEP ([(18)F]-1) and
      [(18)F]F-A-85380 in baboons demonstrated faster brain kinetics of the former
      compound (with a peak uptake at 20 min post injection only). Taken together, the
      preliminary data obtained confirm that [(18)F]FPhEP ([(18)F]-1) has potential for
      in vivo imaging nAChRs in the brain with PET.

PMID- 16455261
TI  - Synthesis of imidazoline and imidazo[2,1-c][1,2,4]triazole aryl derivatives
      containing the methylthio group as possible antibacterial agents.
AB  - 1-Arylimidazolidine-2-thiones (1a-g) were synthesized by the condensation
      reaction of N-arylethylenediamines with carbon disulfide in xylene medium. Their
      further alkylation with methyl iodide led to the formation of some biologically
      active 1-aryl-2-methylthio-imidazolines (2a-g). The 7-(4-methylphenyl)-3
      methylthio-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazole (4b) was obtained by the
      alkylation of the respective 7-(4-methylphenyl)-2,5,6,7-tetrahydroimidazo[2,1
      c][1,2,4]triazol-3(H)-thione (3b) with methyl iodide. Antimicrobial activities of
      1-aryl-2-methylthio-imidazolines (2a-g) and the 7-(4-methylphenyl)-3- methylthio
      5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazole (4b) are presented. All tested
      compounds showed MIC in the range of 11.0-89.2 microM. Compounds 2a,e were found
      to be equipotent to chloramphenicol in vitro, whereas 2a,c,e-g and 4b showed
      superior activity (MIC) to ampicillin.

PMID- 16455262
TI  - Synthesis and pharmacological evaluation of some N-arylsulfonyl-N-methyl-N'-(2,2
      dimethyl-2H-1-benzopyran-4-yl)ureas structurally related to cromakalim.
AB  - Some N-arylsulfonyl-N-methyl-N'-(2,2-dimethyl-2H-1-benzopyran-4-yl)ureas were
      prepared and evaluated as putative potassium channel openers on the vascular and
      uterine smooth muscle tissue (myorelaxant effect), as well as on insulin
      secreting pancreatic islets (inhibition of insulin release). The pharmacological
      results indicated that these compounds exhibited a marked biological activity on
      these three tissues.

PMID- 16455263
TI  - Precision measurements in 124Te following the decay of 124Sb.
AB  - The decay of 124Sb (60 d half-life) to levels of 124Te has been studied using two
      HPGe detectors in singles and coincidence mode. We identify 75 transitions in
      this decay, including 14 gamma rays, the emission of which are being reported
      here for the first time. In confirming the existence of 26 well-established
      levels below 2900 keV excitation, we also introduce 5 other levels at 2490.5,
      2618.4, 2747.05, 2834.99, and 2859.4 keV. The data on energies of gamma
      transitions and the levels are reported at high precision.

PMID- 16455264
TI  - Development and commissioning of a Monte Carlo photon beam model for Varian
      Clinac 2100EX linear accelerator.
AB  - Monte Carlo modeling of a linear accelerator is the first and most important step
      in Monte Carlo dose calculations in radiotherapy. We developed a photon beam
      model for Varian 2100EX for dose calculation purposes using MCNP4C Monte Carlo
      code. Results of our modeling were in close agreement with our measurements. The
      effect of beam width on percentage depth doses and beam profiles was studied. Our
      results showed that electron beam width could be tuned using large field beam
      profile at the depth of maximum dose.

PMID- 16455265
TI  - DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and
      memory defects.
AB  - Among the various phenotypes seen in Down syndrome (DS), mental retardation is
      the most common and most debilitating condition suffered by individuals with DS.
      The DYRK1A gene on human chromosome 21q22.2 encodes a subfamily of protein
      kinases that displays dual substrate specificities and is known to play a
      critical role in neurodevelopment. To study DS mental retardation, we have
      generated transgenic mice that contain only one copy of the complete human DYRK1A
      gene in a bacterial artificial chromosome. The transgenic mice showed significant
      impairment in hippocampal-dependent memory tasks in a Morris water maze.
      Interestingly, we observed shifts in both long-term potentiation and long-term
      depression, which suggests a role for DYRK1A in bidirectional synaptic
      plasticity. These mice represent the most clinically relevant DYRK1A mouse model
      to date and provide us a valuable tool for the in vivo study of mechanisms that
      underlie the learning and memory deficit in DS.

PMID- 16455266
TI  - Effect of low-level helium-neon laser therapy on the healing of third-degree
      burns in rats.
AB  - This paper presents the results of a study on the effects of low-level helium
      neon laser therapy (LL He-Ne LT) on the healing of burns. Seventy-eight adult
      male rats, having been subjected to third-degree burns, were randomly divided
      into four groups: two laser treated groups (n=20, each), one control group (n=19)
      and one nitrofurazone treated group (n=19). In the two laser treated groups, the
      burns were treated on a daily basis with LL He-Ne LT with an energy density of
      1.2 and 2.4 J/cm(2), respectively. The response to treatment was assessed
      histologically at 7, 16 and 30 days after burning, and microbiologically at day
      15. Analysis of variance showed that the mean of blood vessel sections in the
      1.2J/cm(2) laser group was significantly higher than those in the other groups
      and the mean of the depth of new epidermis in the 2.4 J/cm(2) laser group on day
      16 was significantly lower than in the nitrofurazone treated group (P=0.025,
      P=0.047, respectively). When Staphylococcus aureus and Pseudomonas aeruginosa
      grew in more than 50% of samples obtained from control group, there were no S.
      aureus and P. aeruginosa in the samples of 2.4 J/cm(2) laser group. It is
      concluded that LL He-Ne LT induced the destruction of S. aureus and P. aeruginosa
      in third-degree burns of rats, yet at the same time our histological findings
      showed that LL He-Ne LT caused a significant increase in the mean of blood vessel
      sections on day 7 after third degree burns and a decrease in the mean of the
      depth of new epidermis on day 16 after the same burns in rats.

PMID- 16455267
TI  - Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after
      acute treatment with doxorubicin in mice.
AB  - We investigated the expression of the genes for matrix metalloproteinases (MMP)-2
      and MMP-9 in the ventricle for 1, 2 and 4 days after acute treatment with
      doxorubicin (DOX) to induce cardiomyopathy in mice, at a single dose of 25 mg kg(
      1). Ventricle weights, ventricle weight-to-tail length ratios, and left
      ventricular systolic and diastolic internal dimensions all decreased time
      dependently. Histology showed increased vacuolisation of cardiomyocytes in the
      DOX-treated mice on day 4 compared with controls. Northern blot hybridisation
      revealed that MMP-2 and MMP-9 gene transcripts increased in the ventricle of DOX
      treated mice on day 2. MMP-2 mRNA approximately doubled in the DOX-treated mice
      on days 1 and 2, measured using quantitative real-time reverse transcription
      polymerase chain reaction. By contrast, MMP-9 mRNA expression did not differ in
      either group on day 1, whereas it increased significantly to 2.9-fold and 2.1
      fold in the DOX-treated mice on days 2 and 4, respectively. Consequently, MMP-2
      and MMP-9 gene expressions are induced in the ventricle after treatment with DOX,
      indicating that they might play an important role in the development of DOX
      induced cardiotoxicity.

PMID- 16455268
TI  - Functional evaluation of the TKA patient using the coordination and variability
      of rising.
AB  - A kinematic analysis of the knee function is important for the evaluation of
      total knee arthroplasties (TKA). We used the coordination and variability of
      rising from a chair as functional knee parameters. Twelve knee patients were
      measured prior to surgery (=pre-TKA group) and one year after surgery (=post-TKA
      group). A group of 15 healthy, age-matched subjects was selected as control
      group. The WOMAC questionnaire, frequently used by orthopaedic surgeons, was
      administered prior to the test. The test consisted of 10 times rising from a low
      chair and 10 times from a high chair. Knee and hip angles and angular velocities
      were measured with electrogoniometers. The relative phase (=MRP) between hip and
      knee was a measure for the coordination of rising and the standard deviation of
      the relative phase of the 10 trials (=SRP) was a measure for the variability. The
      coordination and variability of rising of the TKA patients were compared to the
      control group, and the relationship with the WOMAC questionnaire was calculated.
      The coordination of rising from a high chair and the variability of rising from
      both chair heights were significantly different for the pre-TKA group compared to
      the control group (p<0.05). The post-TKA group showed no significant differences
      with the control group, which indicates a functional recovery after TKA
      implantation. The functional parameters correlated adequately with the subjective
      WOMAC questionnaire. This study showed that our method is an objective measure of
      functionality and it will be worthwhile to use it as an additional evaluation
      tool.

PMID- 16455269
TI  - Internal arteriovenous fistula within a radial forearm flap--a novel technique to
      increase femorodistal bypass graft flow to the diabetic foot and flap covering
      ischaemic tissue loss.
AB  - BACKGROUND: The fascio-cutaneous radial forearm flap is especially suitable to
      rebuild the contour of the foot, but because of low natural low flow this flap
      lacks the beneficial effect of large muscle flaps on bypass graft flow. The aim
      of this study was to introduce a novel technique of flap coverage combined to
      vascular bypass: an internal av-fistula was created within a radial forearm flap.
      METHODS: Nine critically ischaemic limbs were treated with a modified radial
      forearm flap in the Department of Plastic and Vascular Surgery, Helsinki
      University Central Hospital 1998-2003. All the patients were candidates for a
      major amputation unless this combined operation was attempted. A two-team
      approach was used: the vascular surgeon performed the distal bypass and the
      radial forearm flap was raised by the plastic surgeon. In eight cases a
      femorodistal bypass was performed and in the ninth the vein graft supplied the
      flap directly. The internal fistula within the flap was created between the
      distal end of the radial artery and either the cephalic vein or the concomitant
      vein of the radial artery. Flow was measured during surgery. RESULTS: Vein graft
      flow increased significantly after the radial forearm flap anastomosis (76 vs 44
      ml/min, p=0.016). The flow of both the bypass graft and the flap artery were
      higher with the av-fistula patent (p=0.016 and p=0.004). Graft patency was 89% at
      2 years. Infection was a major cause of amputation, 1- and 2-year limb salvages
      being 67 and 53%. CONCLUSION: In a group of diabetic patients increased flow in a
      vascular bypass graft was achieved by an internal av-fistula within a radial
      forearm flap. This method is useful in selected cases with poor run off and large
      ischaemic lesions.

PMID- 16455270
TI  - A new century of amphibian developmental biology.

PMID- 16455271
TI  - The crtS gene of Xanthophyllomyces dendrorhous encodes a novel cytochrome-P450
      hydroxylase involved in the conversion of beta-carotene into astaxanthin and
      other xanthophylls.
AB  - The conversion of beta-carotene into xanthophylls is a subject of great
      scientific and industrial interest. We cloned the crtS gene involved in
      astaxanthin biosynthesis from two astaxanthin producing strains of
      Xanthophyllomyces dendrorhous: VKPM Y2410, an astaxanthin overproducing strain,
      and the wild type ATCC 24203. In both cases, the ORF has a length of 3166 bp,
      including 17 introns, and codes for a protein of 62.6 kDa with similarity to
      cytochrome-P450 hydroxylases. crtS gene sequences from strains VKPM Y2410, ATCC
      24203, ATCC 96594, and ATCC 96815 show several nucleotide changes, but none of
      them causes any amino acid substitution, except a G2268 insertion in the 13th
      exon of ATCC 96815 which causes a change in the reading frame. A G1470 --> A
      change in the 5' splicing region of intron 8 was also found in ATCC 96815. Both
      point mutations explain astaxanthin idiotrophy and beta-carotene accumulation in
      ATCC 96815. Mutants accumulating precursors of the astaxanthin biosynthetic
      pathway were selected from the parental strain VKPM Y2410 (red) showing different
      colors depending on the compound accumulated. Two of them were blocked in the
      biosynthesis of astaxanthin, M6 (orange; 1% astaxanthin, 71 times more beta
      carotene) and M7 (orange; 1% astaxanthin, 58 times more beta-carotene, 135%
      canthaxanthin), whereas the rest produced lower levels of astaxanthin (5-66%)
      than the parental strain. When the crtS gene was expressed in M7, canthaxanthin
      accumulation disappeared and astaxanthin production was partially restored.
      Moreover, astaxanthin biosynthesis was restored when X. dendrorhous ATCC 96815
      was transformed with the crtS gene. The crtS gene was heterologously expressed in
      Mucor circinelloides conferring to this fungus an improved capacity to synthesize
      beta-cryptoxanthin and zeaxanthin, two hydroxylated compounds from beta-carotene.
      These results show that the crtS gene is involved in the conversion of beta
      carotene into xanthophylls, being potentially useful to engineer carotenoid
      pathways.

PMID- 16455272
TI  - The role of tip-localized mitochondria in hyphal growth.
AB  - Hyphal tip-growing organisms have a high density of tip-localized mitochondria
      which maintain a membrane potential based on Rhodamine 123 fluorescence, but do
      not produce ATP based on the absence of significant oxygen consumption. Two
      possible roles of these mitochondria in tip growth were examined: Calcium
      sequestration and biogenesis, because tip-high cytoplasmic calcium gradients are
      a common feature of tip-growing organisms, and the volume expansion as the tip
      extends would require a continuous supply of additional mitochondria. Co
      localization of calcium-sensitive fluorescent dye and mitochondria-specific
      fluorescent dyes showed that the tip-localized mitochondria do contain calcium,
      and therefore, may function in calcium clearance from the cytoplasm. Short-term
      inhibition of DNA synthesis or mitochondrial protein synthesis did not affect
      either tip growth, or mitochondrial shape or distribution. Therefore,
      mitochondrial biogenesis may not occur from the tip-localized mitochondria in
      hyphal organisms.

PMID- 16455273
TI  - Genomic response programs of Candida albicans following protoplasting and
      regeneration.
AB  - Transcription profiling of Candida albicans cells responding to the elimination
      of the wall (protoplasts) and posterior regeneration was explored. DNA
      microarrays were used to measure changes in the expression of 6039 genes, and the
      upregulated genes during regeneration at 28 degrees C were assigned to fourteen
      categories. A total of 407 genes were upregulated during the process, of which
      144 reached a maximum after 1 h. MKC1, a gene encoding a member of the regulatory
      pathway involved in cell wall integrity was overexpressed. Time-dependent
      expression divided the genes into 40 clusters. Clusters 1-19 were highly
      expressed initially (time 0) and downregulated following incubation, whereas
      transcription of the genes grouped into clusters 20-40 showed the opposite
      behaviour. These results suggest that the first clusters group genes permitting
      the cell adaptation to a sub-optimal environment due to removal of the wall,
      whereas the second group represents genes required for protoplasts regeneration
      after shifted to optimal conditions from 4 to 28 degrees C.

PMID- 16455274
TI  - A cDNA-AFLP based strategy to identify transcripts associated with avirulence in
      Phytophthora infestans.
AB  - Expression profiling using cDNA-AFLP is commonly used to display the
      transcriptome of a specific tissue or developmental stage. Here, cDNA-AFLP was
      used to identify transcripts in a segregating F1 population of Phytophthora
      infestans, the oomycete pathogen that causes late blight. To find transcripts
      derived from putative avirulence (Avr) genes germinated cyst cDNA from F1 progeny
      with defined avirulence phenotypes was pooled and used in a bulked segregant
      analysis (BSA). Over 30,000 transcript derived fragments (TDFs) were screened
      resulting in 99 Avr-associated TDFs as well as TDFs with opposite pattern. With
      142 TDF sequences homology searches and database mining was carried out. cDNA
      AFLP analysis on individual F1 progeny revealed 100% co-segregation of four TDFs
      with particular AVR phenotypes and this was confirmed by RT-PCR. Two match the
      same P. infestans EST with unknown sequence and this is a likely candidate for
      Avr4. The other two are associated with the Avr3b-Avr10-Avr11 locus. This
      combined cDNA-AFLP/BSA strategy is an efficient approach to identify Avr
      associated transcriptome markers that can complement positional cloning.

PMID- 16455275
TI  - Modulation of MCP-1 and iNOS by 50-Hz sinusoidal electromagnetic field.
AB  - The purpose of this study was to investigate whether overnight exposure to 1 mT
      50 Hz extremely low-frequency sinusoidal electromagnetic field (EMF) affects the
      expression and production of inducible nitric oxide synthase (iNOS) and monocyte
      chemotactic protein-1 (MCP-1) in human monocytes. RT-PCR and Western blot
      analysis demonstrate that EMF exposure affects the expression of iNOS and MCP-1
      in cultured human mononuclear cells at the mRNA level and protein synthesis.
      Interestingly, the effects of EMF exposure clearly differed with respect to the
      potentiation and inhibition of iNOS and MCP-1 expression. Whereas iNOS was down
      regulated both at the mRNA level and at the protein level, MCP-1 was up
      regulated. These results provide helpful information regarding the EMF-mediated
      modulation of the inflammatory response in vivo. However, additional studies are
      necessary to demonstrate that EMF acts as a nonpharmacological inhibitor of NO
      and inducer of MCP-1 in some diseases where the balance of MCP-1 and NO may be
      important.

PMID- 16455276
TI  - A serological study on Brucella abortus, caprine arthritis-encephalitis virus and
      Leptospira in dairy goats in Rio de Janeiro, Brazil.
AB  - In spite of the large number of goats found in several developing tropical
      countries, milk production remains unsatisfactory. The occurrence of infectious
      diseases, such as leptospirosis, brucellosis and caprine arthritis-encephalitis
      (CAE) may in part be responsible for sub-optimal production. In this study, 1000
      serum samples were tested for leptospirosis, 953 for brucellosis and 562 for CAE.
      All tested flocks presented at least one seroreactive animal for leptospirosis
      and for CAE. Reactivity to leptospirosis was 11.1%, and serovar hardjo was the
      most frequently found. Anti-B. abortus agglutinins were found in 0.5% of the
      samples presented and 14.1% were seroreactive to CAE. Leptospirosis was
      considered to represent the major infectious problem in the studied goat flocks.
      The occurrence of infectious diseases in the tested flocks may represent an
      important factor contributing to the decreased productivity of the animals. These
      findings may be similar to those observed in other developing countries and
      require further study to define the relationship between seropositivity and
      reduced production.

PMID- 16455277
TI  - Molecular cloning of estrogen receptor alpha of the Nile crocodile.
AB  - Estrogens are essential for normal reproductive activity in female and male
      vertebrates. In female reptiles, they are essential for ovarian differentiation
      during a critical developmental stage. To understand the molecular mechanisms of
      estrogen action in the Nile crocodile (Crocodylus niloticus), we have isolated
      cDNA encoding the estrogen receptor alpha (ERalpha) from the ovary. Degenerate
      PCR primers specific to ER were designed and used to amplify Nile crocodile cDNA
      from the ovary. The full-length Nile crocodile ERalpha cDNA was obtained using 5'
      and 3' rapid amplification cDNA ends (RACE). The deduced amino acid sequence of
      the Nile crocodile ERalpha showed high identity to the American alligator ERalpha
      (98%), caiman ER (98%), lizard ER (82%) and chicken ERalpha (92%), although
      phylogenetic analysis suggested profound differences in the rate of sequence
      evolution for vertebrate ER sequences. Expression of ERalpha was observed in the
      ovary and testis of juvenile Nile crocodiles. These data provide a novel tool
      allowing future studies examining the regulation and ontogenic expression of
      ERalpha in crocodiles and expands our knowledge of estrogen receptor evolution.

PMID- 16455278
TI  - Effect of fasting on carbohydrate metabolism in frugivorous bats (Artibeus
      lituratus and Artibeus jamaicensis).
AB  - The compensatory changes of carbohydrate metabolism induced by fasting were
      investigated in frugivorous bats, Artibeus lituratus and Artibeus jamaicensis.
      For this purpose, plasma levels of glucose and lactate, liver and muscle glycogen
      content, rates of liver gluconeogenesis and the activity of related enzymes were
      determined in male bats. After a decrease during the first 48 h of fasting,
      plasma glucose levels remained constant until the end of the experimental period.
      Plasma lactate levels, extremely high in fed bats, decreased after 48 h of
      fasting. Similarly, liver glycogen content, markedly high in fed animals, was
      reduced to low levels after 24 h without food. Muscle glycogen was also reduced
      in fasted bats. The expected increase in liver gluconeogenesis during fasting was
      observed after 48 h of fasting. The activities of liver glucose-6-phosphatase and
      fructose-1,6-bisphosphatase were not affected by food withdrawn. On the other
      hand, fasting for 24 h induced an increase in the activity of liver cytosolic
      phosphoenolpyruvate carboxykinase. The data indicate that liver gluconeogenesis
      has an important role in the glucose homeostasis in frugivorous bats during
      prolonged periods of food deprivation. During short periods of fasting liver
      glycogenolysis seems to be the main responsible for the maintenance of glycemia.

PMID- 16455279
TI  - Identification and characterization of an interleukin-15 homologue from Tetraodon
      nigroviridis.
AB  - Interleukin-15 (IL-15) plays an important role in adaptive immune systems in
      vertebrates with similar bioactivities to interleukin-2 (IL-2). Here we report
      molecular cloning, sequence analysis and distribution of an IL-15 homologue from
      a pufferfish (Tetraodon nigroviridis). It is located within a 3,088 bp genomic
      fragment, transcribed into a 1,056 bp mRNA including 158 bp 5'UTR (untranslated
      region), 519 bp ORF (open reading frame) and 379 bp 3'UTR. T. nigroviridis IL-15
      is constitutively detectable in tissues and organs selected. Levels of
      transcripts were observed after various stimulations. Gene organization is
      similar to mammals and birds, and a high degree of conservation of chromosome
      synteny exists between them. Systematic genomics search against Takifugu rubripes
      genome supports our conclusions. The T. nigroviridis IL-15 precursor with 172aa
      (amino acids) contains a putative 53aa signal peptide, while the mature peptide
      has a calculated molecular mass of 13.36 kDa and a theoretical pI of 4.67. The
      protein sequence shares 13.3-62.1% identity with reported IL-15s. Phylogenetic
      analysis grouped Tetraodon with other fish on a separated branch, excluded from
      mammalian and avian IL-15s. In addition, our analysis on another annotated T.
      nigroviridis IL-15 demonstrated that it may be a paralogue of IL-15. To
      differentiate it from the known IL-15s, we described it as IL-15x.

PMID- 16455280
TI  - Seasonal changes of nucleotides in mussel (Mytilus galloprovincialis) mantle
      tissue.
AB  - Seasonal variations of nucleotides in Mytilus galloprovincialis mantle tissue
      were analyzed. Separation and quantification was achieved by reversed-phase high
      performance liquid chromatography. Total nucleotides show a pronounced seasonal
      variation with maximum and minimum values in autumn and spring, respectively.
      Adenine nucleotides accounted for the major part in spring and summer, guanosine
      and cytidine nucleotides in winter; uridine nucleotides were relatively constant
      throughout the year. Their inverse variation suggests inter-conversion among them
      and the maintenance of the potential cell energy in winter by other triphosphate
      nucleotides different from ATP. These results reflect environmental and
      nutritional conditions, and also the reserves and gametogenic cycles taking place
      in M. galloprovincialis mantle tissue.

PMID- 16455281
TI  - Characterization of two D-beta-hydroxybutyrate dehydrogenase populations in heavy
      and light mitochondria from jerboa (Jaculus orientalis) liver.
AB  - Mitochondrial membrane-bound and phospholipid-dependent D-beta-hydroxybutyrate
      dehydrogenase (BDH) (EC 1.1.1.30), a ketone body converting enzyme in
      mitochondria, has been studied in two populations of mitochondria (heavy and
      light) of jerboa (Jaculus orientalis) liver. The results reveal significant
      differences between the BDH of the two mitochondrial populations in terms of
      protein expression, kinetic parameters and physico-chemical properties. These
      results suggest that the beta-hydroxybutyrate dehydrogenases from heavy and light
      mitochondria are isoform variants. These differences in BDH distribution could be
      the consequence of cell changes in the lipid composition of the inner
      mitochondrial membrane of heavy and light mitochondria. These changes could
      modify both BDH insertion and BDH lipid-dependent catalytic properties.

PMID- 16455282
TI  - US/O3 combination degradation of aniline in aqueous solution.
AB  - The influencing factors and mechanism of ultrasound (US)/ozone (O3) combination
      degradation of aniline in water were investigated. An increment of approximately
      64% of aniline reduction and 110% of TOC reduction were observed with respect to
      the addition of the separated O3 and US systems, proving US/O3 technology had
      significant synergetic effects. Excellent removal performance was observed in the
      degradation with US/O3. With the initial concentration of aniline at 100 mg l(
      1), the energy density of ultrasound at 0.1 W ml(-1) and the flow rate of ozone
      at 2 mg min(-1), the removal efficiency of aniline would be at least 82% and that
      of TOC would be at least 20% after reaction for 5 min. Major by-products included
      nitrobenzene, p-benzoquinone, p-aminophenol, carboxylic acid, etc.

PMID- 16455283
TI  - Synthesis of oximes under ultrasound irradiation.
AB  - The condensation of aldehydes and ketones with hydroxylamine hydrochloride
      results oximes in 50.7-98.7% yields in EtOH under ultrasound irradiation.
      Compared with conventional methods, the main advantages of the present procedure
      are milder conditions, shorter reaction time and higher yields.

PMID- 16455284
TI  - Observations of water cavitation intensity under practical ultrasonic cleaning
      conditions.
AB  - In the industrial cleaning processes either organic solvents or water solutions
      are used as the cleaning media. The primary causative factor of ultrasonic
      cleaning is cavitation. Below are presented results of investigations into the
      influence of temperature, gas content and the solution level in an ultrasonic
      cleaner on cavitation intensity in the tap water. Previous investigations have
      revealed a great deal of information on the influence of the above factors on the
      cavitation intensity and these are confirmed. It has now been found that the tap
      water reaches the highest cavitation intensity at temperatures below 20 degrees C
      but during heating at higher temperatures (20-40 degrees C) a second peak of
      cavitation intensity may appear-depending on the height of water in the bath and
      air content.

PMID- 16455285
TI  - Osteogenic activity of vanadyl(IV)-ascorbate complex: evaluation of its mechanism
      of action.
AB  - We have previously shown that different vanadium(IV) complexes regulate
      osteoblastic growth. Since vanadium compounds are accumulated in vivo in bone,
      they may affect bone turnover. The development of vanadium complexes with
      different ligands could be an alternative strategy of use in skeletal tissue
      engineering. In this study, we have investigated the osteogenic properties of a
      vanadyl(IV)-ascorbate (VOAsc) complex, as well as its possible mechanisms of
      action, on two osteoblastic cell lines in culture. VOAsc (2.5-25 microM)
      significantly stimulated osteoblastic proliferation (113-125% basal, p<0.01) in
      UMR106 cells, but not in the MC3T3E1 cell line. VOAsc (5-100 micrioM) dose
      dependently stimulated type-I collagen production (107-156% basal) in
      osteoblasts. After 3 weeks of culture, 5-25 microM VOAsc increased the formation
      of nodules of mineralization in MC3T3E1 cells (7.7-20-fold control, p<0.001).
      VOAsc (50-100 microM) significantly stimulated apoptosis in both cell lines (170
      230% basal, p<0.02-0.002), but did not affect reactive oxygen species production.
      The complex inhibited alkaline and neutral phosphatases from osteoblastic
      extracts with semi-maximal effect at 10 microM doses. VOAsc induced the
      activation and redistribution of P-ERK in a time- and dose-dependent manner.
      Inhibitors of the mitogen activated protein kinases (MAPK) pathway (PD98059 and
      UO126) partially blocked the VOAsc-enhanced osteoblastic proliferation and
      collagen production. In addition, wortmanin, a PI-3-K inhibitor and type-L
      channel blocker nifedipine also partially abrogated these effects of VOAsc on
      osteoblasts. Our in vitro results suggest that this vanadyl(IV)-ascorbate complex
      could be a useful pharmacological tool for bone tissue regeneration.

PMID- 16455286
TI  - Intratumor genomic heterogeneity correlates with histological grade of advanced
      oral squamous cell carcinoma.
AB  - To assess the difference in genetic aberration patterns among the invasive tumor
      front (ITF), center/superficiality and the stroma adjacent to oral squamous cell
      carcinoma (OSCC), we studied loss of heterozygosity (LOH) and microsatellite
      instability (MI) at chromosome 9p21 and 17p13 on the three regions by combining
      laser capture microdissection (LCM) and PCR. We studied 20 OSCC patients with
      TP53 on chromosome 17p13 and RPS6 on chromosome 9p21. Genomic DNA samples from
      the ITF, center/superficial and stromal cells adjacent to the tumor were prepared
      from cryosections using laser-assistant microdissection, then LOH and MI were
      determined. Cells at the ITF, center/superficiality and stroma showed a high
      frequency of LOH and MI on chromosomes 17p13 (TP53) and 9p21 (RPS6). Comparison
      of the patterns of allelic loss and MI encountered at the ITF, center/superficial
      and stromal cells revealed no concordance. The frequency of RPS6 and TP53
      aberration at the epithelial compartment (both ITF and center, 64.7%, 11/17;
      70.6%, 12/17) was statistically higher than the stroma (23.5%, 4/17; 43.8%, 7/16)
      (p<0.05). Furthermore, for the epithelial compartment, the aberrations
      proportions of TP53 rose from 60.0% (9/15) to 64.7% (11/17) between the
      center/superficial part and ITF. Also the rate of RPS6 increased from 29.4%
      (5/17) to 58.8% (10/17) between the center/superficial parts and ITF. The overall
      frequency of the two markers was statistically higher at the ITF (20/32) than the
      center/superficial part (15/34) (p<0.05). The current study revealed that
      intratumor genetic heterogeneity exists in the different histological areas of
      OSCCs and some particular tumor cell genotypes have correlation with histological
      patterns.

PMID- 16455287
TI  - Recurrence and salvage treatment of squamous cell carcinoma of the oral cavity.
AB  - The aim of this study was to evaluate the incidence and predictive factors for
      recurrence of oral squamous cell carcinoma (SCC) and outcome according to salvage
      treatment modality. A retrospective analysis of 127 oral cavity cancer patients
      who underwent surgery with or without postoperative radiotherapy as initial
      treatment was performed. Thirty-six patients (28%) were observed with recurrences
      and/or metastases mostly at the primary site and neck. Seventy-eight percent of
      recurrences occurred within one year, and 92% within two years after the initial
      treatment. The rate of recurrence and/or metastases was significantly higher in
      patients with an advanced pathologic stage, pathologic lymph node and positive
      resection margin compared to those with an early pathologic stage, negative lymph
      node and negative resection margin (p<0.05). Especially, regarding the
      relationship between the rate of locoregional recurrence and local or regional
      factors, resection margin status was a particularly important, and potentially
      preventable, independent predictor for locoregional control. Patients who
      underwent salvage surgery with or without postoperative radiotherapy had
      significantly improved salvage and total survival times compared with patients
      who received chemotherapy and/or radiation therapy for their recurrence.

PMID- 16455288
TI  - Efficacy of a novel lubricating system in the management of radiotherapy-related
      xerostomia.
AB  - A comparison was made of Oral Balance gel delivered by slow release via a novel
      intra-oral device versus an oral bolus of gel on the oral health condition and
      oral health-related quality of life (OHRQoL) in patients who had received
      standard head and neck irradiation for nasopharyngeal carcinoma. Twenty-two
      participants took part in a randomized single-blind crossover clinical study.
      Each treatment lasted 4 weeks with an intervening 4 weeks washout period. The
      GOHAI, Xerostomia Inventory and patient satisfaction measures were self-completed
      and oral health condition assessed objectively at baseline (week 0) and weeks 4,
      8 and 12. Oral Balance gel, in bolus and slow-release forms, was effective in
      improving aspects of oral health, notably a reduction in oral cariogenic micro
      organisms. Slow release of gel via the intra-oral device did not appear to
      improve OHRQoL whereas gel alone reduced the severity of xerostomia symptoms and
      was the treatment of choice.

PMID- 16455289
TI  - Chemometrics-assisted simultaneous determination of cobalt(II) and chromium(III)
      with flow-injection chemiluminescence method.
AB  - In this paper, a flow-injection chemiluminescence (CL) system is proposed for
      simultaneous determination of Co(II) and Cr(III) with partial least squares
      calibration. This method is based on the fact that both Co(II) and Cr(III)
      catalyze the luminol-H(2)O(2) CL reaction, and that their catalytic activities
      are significantly different on the same reaction condition. The CL intensity of
      Co(II) and Cr(III) was measured and recorded at different pH of reaction medium,
      and the obtained data were processed by the chemometric approach of partial least
      squares. The experimental calibration set was composed with nine sample solutions
      using orthogonal calibration design for two component mixtures. The calibration
      curve was linear over the concentration range of 2 x 10(-7) to 8 x 10(-10) and 2
      x 10(-6) to 4 x 10(-9) g/ml for Co(II) and Cr(III), respectively. The proposed
      method offers the potential advantages of high sensitivity, simplicity and
      rapidity for Co(II) and Cr(III) determination, and was successfully applied to
      the simultaneous determination of both analytes in real water sample.

PMID- 16455290
TI  - Aluminium complexes in methanol-water mixture as studied by 27Al NMR nuclear
      magnetic resonance.
AB  - (27)Al NMR spectroscopy can be used for study of coordination and solvation in
      both aqueous and non-aqueous solutions. Various octahedral and tetrahedral
      aluminium complexes have been proved to exist in solution by (1)H and (27)Al NMR
      spectroscopy. (27)Al nuclear magnetic resonance (NMR) spectroscopy also can be
      used to determine thermodynamic properties of complexes in the solution. The
      formation of [Al(OH)(4-n)(CH(3)OH)(n)]((n-1)+) (n=1, 2, 3 and 4) species through
      the reaction of aluminate anion with methanol has been investigated by (27)Al NMR
      spectroscopy. (27)Al NMR spectra reveal evidence for Al bound to one, two, three
      and four CH(3)OH, the production of aluminate species is affected by the
      MeOH/H(2)O. Results obtained from 2D EXSY experiments clearly confirm there are
      exchanges among the species.

PMID- 16455291
TI  - UV/vis, 1H, and 13C NMR spectroscopic studies to determine mangiferin pKa values.
AB  - The acid constants of mangiferin (a natural xanthonoid) in aqueous solution were
      determined through an UV/vis spectroscopic study employing the SQUAD program as a
      computational tool. A NMR study complements the pK(a) values assignment and
      evidences a H-bridge presence on 1-C. The chemical model used was consistent with
      the experimental data obtained. The pK(a) values determined with this procedure
      were as follows: H(4)(MGF)=H(3)(MGF)(-)+H(+), pKa1 (6-H)=6.52+/-0.06; H(3)(MGF)(
      )=H(2)(MGF)(2-)+H(+), pKa2 (3-H)=7.97+/-0.06; H(2)(MGF)(2-)=H(MGF)(3-)+H(+), pKa3
      (7-H)=9.44+/-0.04; H(MGF)(3-)=(MGF)(4-)+H(+), pKa4 (1-H)=12.10+/-0.01; where it
      has been considered mangiferin C(19)H(18)O(11) as H(4)(MGF). Mangiferin UV/vis
      spectral behavior, stability study in aqueous solution as well as NMR
      spectroscopy studies: one-dimensional (1)H,(13)C, 2D correlated (1)H/(13)C
      performed by (g)-HSQC and (g)-HMBC methods; are also presented. pK(a) values
      determination of H(4)(MGF) in aqueous solution is a necessary contribution to
      subsequent pharmacokinetic study, and a step towards the understanding of its
      biological effects.

PMID- 16455292
TI  - Normal coordinate analysis and crystal structure of N,N-dimethyl-N'-(2-chloro
      benzoyl)thiourea.
AB  - In the present paper, the crystal structural and vibrational analysis of the N,N
      dimethyl-N'-(2-chloro-benzoyl)thiourea molecule is reported. The molecular
      structure of the title compound was determined by single crystal X-ray
      diffraction method. The compound crystallizes monoclinic, space group P2(1)/c
      with a=5.6601(13)A, b=10.748(2)A, c=17.778(4)A, beta=94.266(5) degrees , and
      V=1078.5(4)A(3) with Z=4 for d(calc)=1.495 g/cm(3). Calculations of the
      vibrational frequencies have been carried out on the basis of normal coordinate
      analysis using simple general valence force field in Wilson's GF matrix method
      with the SPSIM computer program. With the help of this modern technique we were
      able to complete the assignment of the vibrational spectrum of the title
      compound.

PMID- 16455293
TI  - A vibrational and DFT study of M(diimine)(dithiolate) complexes and their
      complexation route.
AB  - A complete vibrational spectra analysis of the Pd(phen)(bdt), the free ligands,
      where phen=1,10-phenanthroline and bdt=1,2-benzenedithiolate and the starting
      material of its synthesis, Pd(phen)Cl(2), is performed in this paper. The
      molecular geometry, binding and spectroscopic properties for the aforementioned
      compounds are studied in detail by FT-IR, Raman and DFT methods using B3LYP
      functional together with basis sets of valence triple-zeta quality. Further,
      changes in FT-IR and Raman spectra during complexation are monitored revealing
      the electron delocalization over ligands. They are also consistent with pi-back
      donation theory.

PMID- 16455294
TI  - IR-SERS study and theoretical analogue on the adsorption behavior of pyridine
      carboxylic acid on silver nanoparticles.
AB  - High qualities Raman spectra of pyridine carboxylic acid in silver colloidal
      solution and on silver-coated ITO glass at near infrared laser excitation were
      obtained in this article. The calculations based on density functional theory
      (DFT) were used to analysis the absorption behavior of these molecules. By
      comparing the experimental frequencies with the calculated ones, it can be
      concluded that the carboxylate-to-metal interaction is the key factor during the
      adsorption process, and the nitrogen-to-metal coordination seemed to play a
      secondary role in the process.

PMID- 16455295
TI  - Spectrophotometric and thermodynamic study on the dimerization equilibrium of
      ionic dyes in water by chemometrics method.
AB  - The monomer-dimer equilibrium and thermodynamic of several ionic dyes (Neutral
      Red, Nile Blue A, Safranine T and Thionine) has been investigated by means of
      spectrophotometric and chemometrics methods. The dimerization constants of these
      ionic dyes have been determined by studying the dependence of their absorption
      spectra on the temperature in the range 20-75 degrees C at concentrations of
      Neutral Red (1.73 x 10(-5) M), Nile Blue A (3.94 x 10(-5) M), Safranine (6.59 x
      10(-5) M) and Thionine (6.60 x 10(-5) M). The monomer-dimer equilibrium of these
      dyes has been determined by chemometrics refinement of the absorption spectra
      obtained by thermometric titrations performed. The processing of the data carried
      out for quantitative analysis of undefined mixtures, based on simultaneous
      resolution of the overlapping bands in the whole set of absorption spectra. The
      enthalpy and entropy of the dimerization reactions were determined from the
      dependence of the equilibrium constants to the temperature (van't Hoff equation).

PMID- 16455296
TI  - C.I. Reactive Orange 16-dodecylpyridinium chloride interactions in electrolytic
      solutions.
AB  - The effect of electrolytes on the interaction between an anionic dye and a
      cationic surfactant was investigated spectrophotometrically in submicellar
      concentration range at certain temperature. The spectral change of the azo dye
      C.I. Reactive Orange 16 (RO16) exhibits a high sensitivity to the polarity of
      dye's environment. Dodecylpyridinium chloride (DPC) affects the electronic
      absorption spectra of dye solution that is dye-surfactant interaction results
      formation of complex and therefore a decrease in maximum absorption spectra
      (1.577 at 494 nm). The electrolyte cations cause an increase of the absorbance of
      DPC-RO16 ion-pair complex in the following order:
      Ca(2+)>Na(+)>NH(4)(+)>K(+)>Mg(2+), also for electrolyte anions Br(-)>Cl(
      )>SO(4)(2-). Furthermore, this order can be changeable with increasing
      electrolyte concentration. The increase on absorbance value with increasing
      electrolyte concentration is explained as charge screening. The increase or
      decrease on absorption spectra of RO16-DPC solution depends on concentration
      range of the electrolyte added. As an increase on absorbance value with
      increasing electrolyte concentration is explained as charge screening, a decrease
      in this value for higher concentration of electrolyte is attributed as the charge
      of micelle shape.

PMID- 16455297
TI  - Evidence for disorder in L-alanine lattice detected by Pulsed-EPR spectroscopy at
      cryogenic temperatures.
AB  - The unusual behavior of lattice dynamics of L-alanine has been assigned to
      intermolecular dynamics and localization of vibrational energy. Recent heat
      capacity and Pulsed-EPR measurements support presence of thermally activated
      dynamic orientational disorder in the L-alanine lattice below 20 K. In the
      present study, the additional evidence for possible thermally activated
      disordered behavior of L-alanine lattice have been obtained by investigating
      dependences of longitudinal relaxation time of first stable L-alanine radical,
      SAR1, on sample cooling rates for the same low temperature interval. The obtained
      relaxation time by Pulsed-EPR shows clear dependence on cooling rates and this
      behavior can be explained within two types of suggested spin-lattice relaxation
      mechanisms for the paramagnetic centers in the hydrogen-bonded organic crystal.

PMID- 16455298
TI  - Pyrromethene dyes (BODIPY) can form ground state homo and hetero dimers:
      photophysics and spectral properties.
AB  - Homo and hetero dimerisation of two spectroscopically different BODIPY
      chromophores was studied, namely, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene and
      its 5-styryl-derivative. These exhibit very similar absorption and fluorescence
      spectral shape, but are mutually shifted by ca. 70 nm. For this reason the former
      and the latter are referred to as the green and red BODIPY, which here are
      denoted gB and rB, respectively. Various spectroscopic properties of the rB in
      different common solvents were determined. The calculated and experimental
      fluorescence quantum yield is found to be close to 100%, the fluorescence
      relaxation has a single exponential decay with a lifetime of about 4.5 ns, and
      the Forster radius for donor-donor energy migration is 67+/-1A. The dimerisation
      in different solvents was examined by using custom synthesised; mono and bis
      BODIPY-labelled forms of 1,2-cis-diaminocyclohexane. It is shown that gB and rB
      can form ground state homo- as well as hetero dimers. The dimers are non
      fluorescent, compatible with H-dimers and may act as excitation traps or as
      acceptors to the corresponding excited monomers.

PMID- 16455299
TI  - Test the artefact--develop the organization. The implementation of an electronic
      medication plan.
AB  - OBJECTIVE AND METHODS: The paper aims to develop further insights into the
      process of implementation of IT in health care by describing findings from a
      study of a trial implementation of a newly developed electronic medication plan
      (EMP) in three hospitals in a county in Denmark. A sociotechnical perspective is
      applied to data acquired by the qualitative methods of participant observation
      and semi-structured open-ended interviews. CONCLUSIONS: The achievement of fit
      between IT technology and work processes in health care involves the
      establishment of new organizational structures that cut across the existing
      divisionalized hospital organization and a detailed alignment of artefact,
      functionality and work process. This process can be furthered by supporting
      'communities of practice', i.e. informal groups of engaged clinicians. A
      sociotechnical perspective is beneficial to the analysis of such processes.

PMID- 16455300
TI  - Development of an improved method of detection of infectious parvovirus B19.
AB  - BACKGROUND: Parvovirus B19, the only known pathogenic human parvovirus is the
      aetiologic agent of erythema infectiosum, transient aplastic crisis, pure red
      cell aplasia, and hydrops fetalis. Transmission is either by respiratory
      secretions or, as it can be present at high titre in plasma, by blood and blood
      products. B19 is only cultured with difficulty in vitro, and there is no readily
      available assay for detecting B19 infectivity or neutralizing antibodies.
      OBJECTIVES: In this study, we evaluated different methods to detect viral
      infection for the purpose of developing automated methods for large-scale testing
      of viral infectivity, development of neutralizing antibody and viral inactivation
      assays. STUDY DESIGN: Different cell lines were evaluated for their ability to
      support B19 infection and assays tested for sensitivity and ease of performing. A
      high-throughput assay was validated by determining infectious virus in blood
      pools and for determining neutralizing antibody in sera. RESULTS: B19 protein
      production was detected by immunofluorescence (IF) staining and increased viral
      DNA production by dot blot hybridization and quantitative PCR. The detection of
      RNA transcripts by RT-PCR assay and quantitative RT-PCR (qRT-PCR) was used as an
      indirect marker for infection. Of the cell lines tested, the subclone UT7/Epo-S1
      showed the greatest sensitivity to B19 infection, with detection of viral
      transcripts by qRT-PCR the preferred assay. The assays were validated by
      experiments to determine the infectious titre of sera from acutely infected
      humans, to evaluate the presence of infectious virus in human donor plasma pools
      and to measure neutralizing antibodies.

PMID- 16455301
TI  - Emergency surgery due to haematoma in a case of left atrial myxoma.
AB  - Atrial myxomas generally do not require urgent surgery. We report on a 78-year
      old woman in whom transesophageal echography revealed a large left atrial myxoma.
      She acutely developed dyspnoea, tachypnoea, and forward failure necessating
      urgent surgery. The myxoma was surgically removed and showed a haematoma. The
      most likely reason for the deteriorating condition was acute enlargement of the
      myxoma due to intramyxomal haemorrhage. This case illustrates that the clinical
      condition of patients with symptomatic myxoma can deteriorate suddenly and
      require urgent surgical treatment.

PMID- 16455302
TI  - Red blood cells that do and red blood cells that don't: how to resist a
      persistent parasite.
AB  - Sixty years ago, Haldane proposed that certain abnormalities in red blood cells
      could be selected as malaria-resistance genes. Population studies have confirmed
      that many human polymorphisms confer resistance to severe malaria, although the
      mechanisms of protection remain unknown. A recent article proposes a new
      mechanism for explaining the protective effects of hemoglobin C (HbC). HbC
      containing red blood cells have modified displays of malaria surface proteins
      that reduce parasite adhesiveness and could reduce the risk of severe disease.

PMID- 16455303
TI  - What causes lymphocyte hyporesponsiveness during filarial nematode infection?
AB  - Filarial nematodes persist in the parasitized host by modulating immune
      responsiveness. A feature of this that has been observed in a multitude of
      studies dating back several decades is an inability of lymphocytes to respond
      appropriately to filarial nematode antigens and, in some cases, to other stimuli.
      The consistency of this observation, allied to the ease of measurement of
      lymphocyte hyporesponsiveness, has resulted in many attempts to understand its
      cause.

PMID- 16455304
TI  - Role of SCC-S2 in experimental metastasis and modulation of VEGFR-2, MMP-1, and
      MMP-9 expression.
AB  - SCC-S2/GG2-1/NDED (approved gene symbol TNFAIP8) is a transcription factor NF
      kappaB-inducible, antiapoptotic, and oncogenic molecule. In this study, we
      examined the role of SCC-S2 in invasion and experimental metastasis. We
      demonstrate that expression of SCC-S2 cDNA in MDA-MB 435 human breast cancer
      cells is associated with enhanced invasion in vitro and increased frequency of
      pulmonary colonization of tumor cells in athymic mice. Systemic treatment of
      athymic mice with a cationic liposomal formulation of SCC-S2 antisense oligo led
      to decreased incidence of pulmonary metastasis and inhibition of SCC-S2
      expression in vivo. Antisense inhibition of endogenous SCC-S2 expression
      correlated with decreased expression of VEGF receptor-2 in tumor cells and human
      lung microvascular endothelial cells and loss of endothelial cell viability. In
      addition, downregulation of SCC-S2 expression in tumor cells was associated with
      decreased expression of known metastasis-related molecules MMP-1 and MMP-9. These
      results demonstrate a novel role for SCC-S2 in tumor progression, involving
      multiple effectors, and provide a basis for SCC-S2-targeted cancer gene therapy.

PMID- 16455305
TI  - Insights from molecular investigations of traditional Chinese herbal stroke
      medicines: implications for neuroprotective epilepsy therapy.
AB  - Traditional Chinese herbal medicine is the most widely practiced form of
      herbalism worldwide. It is based on a sophisticated system of medical theory and
      practice that is distinctly different from orthodox Western scientific medicine.
      Most traditional therapeutic formulations consist of a combination of several
      drugs. The combination of multiple drugs is thought to maximize therapeutic
      efficacy by facilitating synergistic actions and ameliorating or preventing
      potential adverse effects while at the same time aiming at multiple targets.
      Orthodox drug therapy has been subject to critical analysis by the "evidence
      based medicine" movement, and demands have been made that herbal medicine should
      be subject to the same kind of scrutiny. However, evaluation of the effectiveness
      of herbal medicines can be challenging, as their active components are often not
      known. Accordingly, it may be difficult to ensure that an herbal preparation used
      in clinical trials contains the components underlying its purported therapeutic
      effect. We reasoned that the identification of actions of herbal medicines at
      well-defined molecular targets and subsequent identification of chemical
      compounds underlying these molecular effects might serve as surrogate markers in
      the hypothesis-guided evaluation of their therapeutic efficacy. A research
      program was initiated to characterize in vitro molecular actions of a collection
      of 58 traditional Chinese drugs that are often used for the treatment of stroke.
      The results indicate that these drugs possess activity at disparate molecular
      targets in the signaling pathways involved in N-methyl-d-aspartate (NMDA)
      receptor-mediated neuronal injury and death. Each herbal drug contains diverse
      families of chemical compounds, where each family comprises structurally related
      members that act with low affinity at multiple molecular targets. The data appear
      to support the multicomponent, multitarget approach of traditional Chinese
      medicine. Glutamate release and excessive stimulation of NMDA receptors cause
      status epilepticus-induced neuronal death and are involved in epileptogenesis.
      Therefore, these results are also relevant to the development of
      antiepileptogenic and neuroprotective therapy for seizures. The combination of
      principles of modern molecular medicine with certain ideas of traditional
      empirical Chinese medicine may be beneficial in translational medicine in
      general.

PMID- 16455306
TI  - Review of randomised trials using the post-randomised consent (Zelen's) design.
AB  - BACKGROUND: In 1979, Zelen described a trial method of randomising participants
      before acquiring consent in order to enhance recruitment to clinical trials. The
      method has been criticised ethically due to lack of consent and scientifically
      due to high crossover rates. This paper reviews recent published trials using
      this method and describes the reasons authors gave for using the method, examines
      the crossover rates, and looks at the quality of identified trials. METHODS:
      Literature review searching for all citations to the relevant Zelen's papers of
      trials published since 1990 plus inclusion of trials from personal knowledge.
      RESULTS: We identified 58 relevant trials. The most common justification for the
      use of Zelen method was to avoid the introduction of bias (e.g., to avoid the
      Hawthorne effect). Few trialists had explicitly used the design to enhance
      participant recruitment. Most trials (n=41) experienced some crossover from one
      group to the other (median crossover=8.9%, mean=13.8%, IQR 2.6% to 15%) although
      this was usually within acceptable limits. CONCLUSION: The most important reason
      stated by authors for using Zelen's method was to limit bias. Zelen's method, if
      carefully used, can avoid 'resentful demoralisation' and the Hawthorne effect
      biasing a trial. Unlike a previous review, we found that crossover was not a
      problem for most trials.

PMID- 16455307
TI  - The effect of direct autonomic nerve stimulation on left ventricular force in the
      isolated innervated Langendorff perfused rabbit heart.
AB  - The relative contribution of the chronotropic effects of stimulating sympathetic
      and vagus nerves on cardiac inotropic changes in the isolated Langendorff
      perfused rabbit heart with intact dual autonomic nerves was studied. The force
      frequency relationship was investigated, in addition to sympathetic nerve
      stimulation (SS) at 2 Hz (low), 5 Hz (med) and 10 Hz (high), and left and right
      vagus nerve stimulation (VS) studied at 2 Hz (low), 5 Hz (med) and 7 Hz (high)
      with and without right ventricular pacing. It was shown that a biphasic force
      frequency relationship is present with a positive relationship at low heart rates
      and a negative force-frequency relationship at higher heart rates. There was a
      trend for left- and right-VS to decrease left ventricular pressure with a
      decrease in heart rate, whilst SS had the opposing effects in a frequency
      dependent manner. When heart rate was kept constant, there was no effect from
      left- or right-VS, while SS increased left ventricular pressure in a frequency
      dependent manner. Together these results suggest that SS, left- and right-VS
      alter left ventricular force by two different mechanisms. Left- and right-VS
      decrease left ventricular pressure predominantly via chronotropic effects whilst
      SS increases force predominantly by direct changes in contractility.

PMID- 16455308
TI  - Dynamics of heart differentiation, visualized utilizing heart enhancer elements
      of the Drosophila melanogaster bHLH transcription factor Hand.
AB  - Drosophila melanogaster has become one of the important model systems to
      investigate the development and differentiation of the heart. After 24h after egg
      deposition (h AED), a simple tube-like organ is formed, consisting of essentially
      only two cell types, the contractile cardioblasts and non-myogenic pericardial
      cells. In contrast to the detailed knowledge of heart formation during
      embryogenesis, only a few studies deal with later changes in heart morphology
      and/or function. This is mainly due to the difficulties to carry out whole mount
      stainings in later stages without complicated dissections or treatments of the
      cuticle and puparium. In this paper we describe the identification of a hand
      genomic region, which is fully sufficient to drive GFP expression in heart cells
      of embryos, larvae, and adults. This serves as an initial step to understand the
      position of hand in the early regulatory network in heart development.
      Furthermore, we demonstrate that our newly created GFP reporter line is extremely
      useful to study postembryonic heart differentiation. For the first time we
      document heart differentiation in living animals throughout all developmental
      stages of Drosophila melanogaster, including embryogenesis, all three larval
      stages, metamorphosis, and the adult life with respect to pericardial cells and
      cardiomyocytes.

PMID- 16455309
TI  - Characterization of the retinoic acid receptor genes raraa, rarab and rarg during
      zebrafish development.
AB  - Retinoic acid signaling is important for patterning the central nervous system,
      paired appendages, digestive tract, and other organs. To begin to investigate
      retinoic acid signaling in zebrafish, we determined orthologies between zebrafish
      and tetrapod retinoic acid receptors (Rars) and examined the expression patterns
      of rar genes during embryonic development. Analysis of phylogenies and conserved
      syntenies showed that the three cloned zebrafish rar genes include raraa and
      rarab, which are co-orthologs of tetrapod Rara, and rarg, which is the zebrafish
      ortholog of tetrapod Rarg. We did not, however, find an ortholog of Rarb. RNA in
      situ hybridization experiments showed that rarab and rarg, are maternally
      expressed. Zygotic expression of raraa occurs predominantly in the hindbrain,
      lateral mesoderm, and tailbud. Zygotic expression of rarab largely overlaps that
      of raraa, except that in later stages rarab is expressed more broadly in the
      brain and in the pectoral fin bud and pharyngeal arches. Zygotic expression of
      zebrafish rarg also overlaps the other two genes, but it is expressed more
      strongly in the posterior hindbrain beginning in late somitogenesis as well as in
      neural crest cells in the pharyngeal arches. Thus, these three genes have largely
      overlapping expression patterns and a few gene-specific expression domains.
      Knowledge of these expression patterns will guide the interpretation of the roles
      these genes play in development.

PMID- 16455310
TI  - Patterns of expression of the three cerebral cavernous malformation (CCM) genes
      during embryonic and postnatal brain development.
AB  - Cerebral Cavernous Malformation (CCM) is a disease characterized by capillary
      venous lesions mostly located in the central nervous system. It occurs both as a
      sporadic and hereditary autosomal dominant condition. Three CCM genes have been
      identified and shown to encode the KRIT1 (CCM1), MGC4607 (CCM2) and PDCD10 (CCM3)
      proteins whose functions are so far unknown. In an attempt to get some insight
      into the role of the 3 CCM genes, we used in situ hybridization to conduct a
      comparative analysis of their expression pattern at several time points during
      murine embryonic, postnatal and adult stages particularly within the central
      nervous system. A strong expression of the 3 Ccm genes was detected in the
      various neuronal cell layers of the brain, cerebellum and spinal cord, from
      embryonic to adult life. By E14.5 a moderate labelling was observed in the heart,
      arterial and venous large vessels with all 3 Ccm probes. Ccm2 and Ccm3 mRNAs, but
      not Ccm1, were clearly detected within meningeal and parenchymal cortical vessels
      at P8. This expression was no more detected by P19 and in adult murine brain,
      strongly suggesting a role for these 2 proteins in the intensive angiogenesis
      process occuring within the central nervous system during this period.

PMID- 16455311
TI  - Specificity of replicative and SOS-inducible DNA polymerases in frameshift
      mutagenesis: mutability of Salmonella typhimurium strains overexpressing SOS
      inducible DNA polymerases to 30 chemical mutagens.
AB  - DNA replication is frequently hindered because of the presence of DNA lesions
      induced by endogenous and exogenous genotoxic agents. To circumvent the
      replication block, cells are endowed with multiple specialized DNA polymerases
      that can bypass a variety of DNA damage. To better understand the specificity of
      specialized DNA polymerases to bypass lesions, we have constructed a set of
      derivatives of Salmonella typhimurium TA1538 harboring plasmids carrying the
      polB, dinB or mucAB genes encoding Escherichia coli DNA polymerase II, DNA
      polymerase IV or DNA polymerase RI, respectively, and examined the mutability to
      30 chemicals. The parent strain TA1538 possesses CGCGCGCG hotspot sequence for -2
      frameshift. Interestingly, the chemicals could be classified into four groups
      based on the mutagenicity to the derivatives: group I whose mutagenicity was
      highest in strain YG5161 harboring plasmid carrying dinB; group II whose
      mutagenicity was almost equally high in strain YG5161 and strain TA98 harboring
      plasmid carrying mucAB; group III whose mutagenicity was highest in strain TA98;
      group IV whose mutagenicity was not affected by the introduction of any of the
      plasmids. Introduction of plasmid carrying polB did not enhance the mutagenicity
      except for benz[a]anthracene. We also introduced a plasmid carrying polA encoding
      E. coli DNA polymerase I to strain TA1538. Strikingly, the introduction of the
      plasmid reduced the mutagenicity of chemicals belonging to groups I, II and III,
      but not the chemicals of group IV, to the levels observed in the derivative whose
      SOS-inducible DNA polymerases were all deleted. These results suggest that (i)
      DNA polymerase IV and DNA polymerase RI possess distinct but partly overlapping
      specificity to bypass lesions leading to -2 frameshift, (ii) the replicative DNA
      polymerase, i.e., DNA polymerase III, participates in the mutagenesis and (iii)
      the enhanced expression of E. coli polA may suppress the access of Y-family DNA
      polymerases to the replication complex.

PMID- 16455312
TI  - Stability of glufosfamide in phosphate buffers and in biological samples.
AB  - Glufosfamide is a new, potential chemotherapeutic agent currently under
      investigation. Stability of glufosfamide was investigated in sodium phosphate
      buffers with different pH and temperature and in biological samples. Glufosfamide
      and isophosphamide mustard were quantified simultaneously using a liquid
      chromatography-ion trap mass spectrometric method; precision and accuracy were
      within 15% for each analyte. Glufosfamide was stable in neutral buffers, but
      decomposed to form isophosphoramide mustard under acidic and basic conditions,
      which was pH- and temperature-dependent. The stability of glufosfamide varied in
      different biological samples. Results indicated that glufosfamide was unstable in
      some biological samples, such as the small intestine, smooth muscles, pancreas
      and urine, especially in the small intestine homogenate, with a half-life of 1.1
      h. But the pH (<8) and beta-glucosidase of the tissue homogenate was found to
      have negligible contribution to the degradation of glufosfamide. The enzymatic
      inhibition experiment with the specific inhibitor, saccharo-1,4-lactone,
      demonstrated that it was glucuronidase that resulted in the degradation of
      glufosfamide in small intestine homogenate. Methanol was recommended to be used
      to homogenize the tissue in an ice water bath, and the container for urine
      collection should also be maintained in an ice water bath, and all the biological
      samples collected should be preserved in frozen condition until analysis.

PMID- 16455313
TI  - Sensitive and specific LC-MS/MS method for the simultaneous measurements of
      viramidine and ribavirin in human plasma.
AB  - Viramidine is a prodrug of ribavirin. To facilitate pharmacokinetics studies of
      viramidine in man, a sensitive and specific LC-MS/MS method for the simultaneous
      analyses of viramidine and ribavirin in human plasma was developed and validated.
      The method involved the addition of [13C]viramidine and [13C]ribavirin as
      internal standards, protein precipitation with acetonitrile, HPLC separation, and
      quantification by MS/MS system using positive electrospray ionization in the
      multiple reaction monitoring mode (MRM). The precursor-->product ion transitions
      were monitored at 245-->113, 250-->113, 244-->112, and 249-->112 for ribavirin,
      [13C]ribavirin, viramidine, and [13C]viramidine, respectively. The calibration
      curves for viramidine and ribavirin were linear over a concentration range of 1
      1000 ng/mL. For both viramidine and ribavirin, the lower limit of quantification
      (LLOQ) was 1 ng/mL. For viramidine, intra- and inter-day analyses of QC samples
      at 1, 5, 250, and 1000 ng/mL indicated good precision (%CV between 1.0 and 7.0%)
      and accuracy (%bias between -4.3 and 5.2%). For ribavirin, intra- and inter-day
      analyses of QC samples at 1, 5, 250, and 1000 ng/mL indicated similar precision
      (%CV between 0.8 and 8.3%) and accuracy (%bias between -5.8 and 9.4%). Both
      viramidine and ribavirin were stable in human plasma stored at room temperature
      for at least 3 h, 4 degrees C for at least 6 h, and for at least three freeze
      thaw cycles. This accurate and highly specific assay provides a useful method for
      evaluating the pharmacokinetics of viramidine and ribavirin in man following
      administration of viramidine.

PMID- 16455314
TI  - Reducing protein concentration range of biological samples using solid-phase
      ligand libraries.
AB  - The discovery of specific polypeptides of diagnostic relevance from a biological
      liquid is complicated by the overall vast number and the large concentration
      range of all polypeptides/proteins in the sample. Depletion or fractionation
      methodologies have been used for selectively removing abundant proteins; however,
      they failed to significantly enrich trace proteins. Here we expand upon a new
      method that allows the reduction of the protein concentration range within a
      complex mixture, like neat serum, through the simultaneous dilution of high
      abundance proteins and the concentration of low abundance ones in a single,
      simple step. This methodology utilizes solid-phase ligand libraries of large
      diversity. With a controlled sample-to-ligand ratio it is possible to modulate
      the relative concentration of proteins such that a large number of peptides or
      proteins that are normally not detectable by classical analytical methods become,
      easily detectable. Application of this method for reducing the dynamic range of
      unfractionated serum is specifically described along with treatment of other
      biological extracts. Analytical surface enhanced laser desorption/ionization mass
      spectrometry (SELDI-MS) technology and mono- and two-dimensional electrophoresis
      (1-DE and 2-DE) demonstrate the increase in the number of proteins detected.
      Examples linking this approach with additional fractionation methods demonstrate
      a further increase in the number of detectable species using either the so-called
      "top down" or "bottom up" approaches for proteomics analysis. By enabling the
      detection of a greater proportion of polypeptides/proteins within a sample, this
      method may contribute significantly towards the discovery of new biomarkers of
      diagnostic relevance.

PMID- 16455315
TI  - Prediction of the binding mode between BMS-378806 and HIV-1 gp120 by docking and
      molecular dynamics simulation.
AB  - BMS-378806 is a newly discovered small molecule that effectively blocks the
      binding of CD4 with gp120. The binding mode of this kind of inhibitor remains
      unknown. In this paper, AutoDock 3.0 in conjunction with molecular dynamics
      simulation, accommodating the receptor's flexibility, was used to explore the
      binding mode between BMS-378806 and gp120. Two structures, Mode I and Mode II,
      with the lowest docking energy were selected as different representative binding
      modes. The analysis of the results from the molecular dynamics simulation
      indicated that the binding of BMS-348806 in Mode II is more stable. The average
      structure of Mode II was analyzed and compared with the experimental data. The
      conclusion was that BMS-378806 inserts the azaindole ring deeply into the PHE43
      cavity and makes contact with a number of residues in the cavity, on the cavity
      and near the cavity. This study benefits the understanding of the mechanism of
      this kind of inhibitor and may provide useful information for rational drug
      design.

PMID- 16455316
TI  - Tryptophanase from Proteus vulgaris: the conformational rearrangement in the
      active site, induced by the mutation of Tyrosine 72 to phenylalanine, and its
      mechanistic consequences.
AB  - Tyr72 is located at the active site of tryptophanase (Trpase) from Proteus
      vulgaris. For the wild-type Trpase Tyr72 might be considered as the general acid
      catalyst at the stage of elimination of the leaving groups. The replacement of
      Tyr72 by Phe leads to a decrease in activity for L-tryptophan by 50,000-fold and
      to a considerable rearrangement of the active site of Trpase. This rearrangement
      leads to an increase of room around the alpha-C atom of any bound amino acid,
      such that covalent binding of alpha-methyl-substituted amino acids becomes
      possible (which cannot be realized in wild-type Trpase). The changes in
      reactivities of S-alkyl-L-cysteines provide evidence for an increase of
      congestion in the proximity of their side groups in the mutant enzyme as compared
      to wild-type enzyme. The observed alteration of catalytic properties in a large
      degree originates from a conformational change in the active site. The Y72F
      Trpase retains significant activity for L-serine, which allowed us to conclude
      that in the mutant enzyme, some functional group is present which fulfills the
      role of the general acid catalyst in reactions associated with elimination of
      small leaving groups.

PMID- 16455317
TI  - Osteoporosis: a still increasing prevalence.
AB  - It is estimated that over 200 million people worldwide have osteoporosis. The
      prevalence of osteoporosis is continuing to escalate with the increasingly
      elderly population. The major complication of osteoporosis is an increase in
      fragility fractures leading to morbidity, mortality, and decreased quality of
      life. In the European Union, in 2000, the number of osteoporotic fractures was
      estimated at 3.79 million. A baseline fracture is a very strong predictor of
      further fractures with 20% of patients experiencing a second fracture within the
      first year. The costs to health care services are already considerable and, on
      current trends, are predicted to double by 2050. The direct costs of osteoporotic
      fractures to the health services in the European Union in the year 2000 were
      estimated at 32 billion Euros. Guidelines for the diagnosis and treatment of
      osteoporosis are available in many countries; however, implementation is
      generally poor despite the availability of treatments with proven efficacy.
      Programs to increase awareness of osteoporosis and its outcomes are necessary for
      healthcare specialists and the general public. Earlier diagnosis and intervention
      prior to the first fracture are highly desirable.

PMID- 16455318
TI  - Strontium ranelate: a physiological approach for an improved bone quality.
AB  - In vitro studies have suggested that strontium ranelate enhances osteoblastic
      cell replication leading to an increase in bone-forming activity. Simultaneously,
      strontium ranelate dose dependently decreases osteoclastic activity. In vivo
      studies indicate that strontium ranelate decreases bone resorption and maintains
      a high bone formation and prevents bone loss. This positive uncoupling between
      bone formation and bone resorption results in bone gain and improvement in bone
      geometry and microarchitecture in growing animals. In intact female rats, a 2
      year period of exposure to strontium ranelate significantly increased bone
      mechanical properties of vertebrae and midshaft femur. All the determinants of
      bone strength were positively influenced by the treatment like bone mass,
      dimension, microarchitecture, and intrinsic bone tissue quality. The increment in
      bone mechanical properties was characterized by an increase in maximal load but
      also by a dramatic improvement in energy to failure, which was essentially due to
      an increment in plastic energy. Such modifications observed with strontium
      ranelate treatment are in good agreement with the improvement in intrinsic bone
      quality. These results strongly suggest that new bone formed following strontium
      ranelate treatment is able to withstand greater deformation before fracture.
      Furthermore, treatment with strontium ranelate prevents the deleterious effect of
      ovariectomy on bone strength. In this model, a 1-year period of exposure to
      strontium ranelate significantly prevents alteration of bone mechanical
      properties of vertebrae in association with a partial preservation of the
      trabecular microarchitecture: a dose-dependent effect on the bone
      volume/trabecular volume ratio and trabecular number and thickness.

PMID- 16455319
TI  - Strontium ranelate: an increased bone quality leading to vertebral antifracture
      efficacy at all stages.
AB  - Strontium ranelate is a new antiosteoporotic treatment with a dual mode of
      action, both increasing bone formation and decreasing bone resorption, which
      rebalances bone turnover in favor of bone formation and increases bone strength.
      The antifracture efficacy of strontium ranelate, 2 g per day orally, in the
      treatment of postmenopausal osteoporosis has been investigated in a large-scale,
      international, multicenter, phase 3 program in which more than 7000 patients were
      recruited. This article deals with the vertebral antifracture efficacy of
      strontium ranelate in postmenopausal women with osteoporosis. A significant early
      (after 1 year) and sustained (over 3 years) antifracture efficacy of strontium
      ranelate, compared with placebo, was demonstrated in patients with prevalent
      vertebral fracture with reductions in risk of new vertebral fracture of 49% after
      1 year (P < 0.001) and 41% over 3 years (P < 0.001). In addition, the relative
      risk of clinical vertebral fracture was significantly reduced by 52% (P = 0.003)
      after 1 year and by 38% (P < 0.001) over 3 years in the strontium ranelate group
      compared with placebo. Strontium ranelate was also demonstrated to significantly
      decrease the relative risk of vertebral fractures by 45% (P < 0.001) in patients
      without prevalent vertebral fracture over 3 years, vs. placebo. Bone mineral
      density was linearly increased during 3 years of treatment with strontium
      ranelate in comparison with placebo. Strontium ranelate was well tolerated
      throughout the entire duration of the clinical trials. Thus, strontium ranelate,
      2 g per day orally, is a new, effective, and safe treatment for postmenopausal
      patients with osteoporosis, to reduce the vertebral fracture risk in patients
      with or without a history of vertebral fracture.

PMID- 16455320
TI  - Physiologic genomics.

PMID- 16455321
TI  - Non-technical skills for surgeons in the operating room: a review of the
      literature.
AB  - BACKGROUND: This review examines the surgical and psychological literature on
      surgeons' intraoperative non-technical skills. These are the critical cognitive
      and interpersonal skills that complement surgeons' technical abilities. The
      objectives of this paper are (1) to identify the non-technical skills required by
      surgeons in the operating room and (2) assess the behavioral marker systems that
      have been developed for rating surgeons' non-technical skills. METHODS: A
      literature search was conducted against a set of inclusion criteria. Databases
      searched included BioMed Central, Medline, EDINA BIOSIS, Web-of-Knowledge,
      PsychLit, and ScienceDirect. RESULTS: A number of "core" categories of non
      technical skills were identified from 4 sources of data: questionnaire and
      interview studies, observational studies, adverse event analyses, and the
      surgical education/competence assessment literature. The main skill categories
      were communication, teamwork, leadership, and decision making. The existing
      frameworks used to measure surgeons' non-technical skills were found to be
      deficient in terms of either their psychometric properties or suitability for
      rating the full range of skills in individual surgeons. CONCLUSIONS: Further work
      is required to develop a valid taxonomy of individual surgeons' non-technical
      skills for training and feedback.

PMID- 16455322
TI  - Assessing the educational environment in the operating room-a measure of resident
      perception at one Canadian institution.
AB  - BACKGROUND: The educational experience in the operating room is considered the
      centerpiece of learning for surgical residents. The educational environment is
      defined as the "ethos" or "climate" that affects all aspects of learning within
      an educational setting. A measure of the educational environment in the operating
      room as perceived by residents would assist educators and trainees in gauging the
      quality of the learning occurring within this important venue. The Operating Room
      Educational Environment Measure (OREEM) was adapted from an inventory validated
      for use with basic surgical trainees in Scotland to determine whether an
      inventory specifically adapted to the specialized environment of the operating
      room can produce a valid assessment of trainee perception of the overall
      educational environment and the contributing factors therein at a North American
      institution. METHODS: The 40-item inventory was piloted on a group of general
      surgery residents at the University of Calgary from November 26, 2003, to January
      31, 2004. RESULTS: With a response rate of 96%, the OREEM was shown to be a
      relevant, internally consistent (Cronbach proportional, variant = .8656) and
      valid tool for assessing the overall educational environment in the operating
      room within a Canadian surgical residency program. Four subscales included
      teaching and training, learning opportunities, atmosphere, and
      workload/supervision/support. The overall mean score of 74% suggests the learning
      environment may be considered satisfactory; however, areas for potential
      improvement are identifiable. Results reveal strengths such as a
      nondiscriminatory operating room atmosphere on racial and gender grounds.
      However, differences were shown in male and female perceptions of learning
      opportunities and in junior versus senior perceptions of workload, supervision,
      and support. CONCLUSIONS: The OREEM has potential to be applied further as a
      quality assessment tool whose results could be used by faculty and program
      directors to improve the learning experiences of residents in the operating room.

PMID- 16455323
TI  - A prospective study of patient safety in the operating room.
AB  - BACKGROUND: To better understand the operating room as a system and to identify
      system features that influence patient safety, we performed an analysis of
      operating room patient care using a prospective observational technique. METHODS:
      A multidisciplinary team comprised of human factors experts and surgeons
      conducted prospective observations of 10 complex general surgery cases in an
      academic hospital. Minute-to-minute observations were recorded in the field, and
      later coded and analyzed. A qualitative analysis first identified major system
      features that influenced team performance and patient safety. A quantitative
      analysis of factors related to these systems features followed. In addition,
      safety-compromising events were identified and analyzed for contributing and
      compensatory factors. RESULTS: Problems in communication and information flow,
      and workload and competing tasks were found to have measurable negative impact on
      team performance and patient safety in all 10 cases. In particular, the counting
      protocol was found to significantly compromise case progression and patient
      safety. We identified 11 events that potentially compromised patient safety,
      allowing us to identify recurring factors that contributed to or mitigated the
      overall effect on the patient's outcome. CONCLUSIONS: This study demonstrates the
      role of prospective observational methods in exposing critical system features
      that influence patient safety and that can be the targets for patient safety
      initiatives. Communication breakdown and information loss, as well as increased
      workload and competing tasks, pose the greatest threats to patient safety in the
      operating room.

PMID- 16455325
TI  - Parathyroidectomy in secondary hyperparathyroidism: Is there an optimal operative
      management?
AB  - BACKGROUND: Subtotal parathyroidectomy (SPTX) and total PTX with
      autotransplantation (TPTX + AT) are both accepted operations for secondary
      hyperparathyroidism (2HPT). Studies have shown the 2 procedures to have similar
      rates of recurrent or persistent HPT (0% to 10%). The majority of these reports
      are small case series and despite apparently similar outcomes; the optimal
      operative management for 2HPT remains controversial. The purpose of this study
      was to determine whether there were any clinical outcome differences between
      these apparently comparable operations. METHODS: A meta-analysis of 53
      publications on reoperative operation for 2HPT from 1983 to 2004 identified 501
      patients who had undergone an operation for recurrent or persistent 2HPT. The
      data evaluated included the type of initial operation, the need for reoperative
      operation as it related to the type of initial operation, and the intraoperative
      findings. RESULTS: The initial operation had been a SPTX in 36% and a TPTX + AT
      in 64% of patients. Reoperative operation was for persistent 2HPT in 82 of 485
      (17%) and for recurrent 2HPT in 403 of 485 (83%) patients. Findings at
      reoperation included: autograft hyperplasia (49%), supernumerary glands (20%),
      remnant hyperplasia (17%), a missed in situ gland (7%), and a negative
      exploration (5%). Supernumerary glands, missed in situ glands, and negative
      explorations occurred at equal rates for both operations. Reoperation determined
      that inadequate cervical explorations occurred in 42% of patients who had
      undergone a SPTX and in 34% of patients who had undergone a TPTX + AT.
      CONCLUSIONS: Operative failures occur because of the limitations in preoperative
      localization, inadequate exploration, and the natural history of hyperplastic
      parathyroid tissue. The initial operation should include an attempt to localize
      supernumerary glands both pre- and intra-operatively.

PMID- 16455326
TI  - Anatomic configurations of the recurrent laryngeal nerve and inferior thyroid
      artery.
AB  - BACKGROUND: Although much attention has been given to the protection of the
      recurrent laryngeal nerve in thyroid surgery, cases of nerve injury are still
      reported occasionally in the literature. In the current study I aimed to describe
      variable relationships between the recurrent laryngeal nerve and inferior thyroid
      artery, and also document my findings in the form of high-resolution photographs.
      METHODS: Fifty specimens (100 sides) were examined for this project, including 36
      male and 14 female cadavers between the ages of 38 and 87 years at death.
      RESULTS: A total of 100 sides were investigated, and 100 recurrent laryngeal
      nerves and 96 inferior thyroid arteries were encountered. I observed a highly
      variable relationship between the nerve and the artery. According to the location
      of the main trunk of the nerve and its branches entering to the larynx, I
      observed 20 types configurations. On the right, the nerve was frequently in front
      of the artery, and on the left the nerve was often behind the 2 branches of the
      artery. CONCLUSION: The relationship of the recurrent laryngeal nerve to the
      inferior thyroid artery is highly variable. Achieving a safe and effective
      operation on the thyroid gland is the goal of all surgeons. I imagine that to
      avoid any injury to the nerve in thyroid surgery demands a thorough knowledge of
      all types of relationships between them.

PMID- 16455327
TI  - Microscopically incomplete resection offers acceptable palliation in pancreatic
      cancer.
AB  - BACKGROUND: Because mortality and morbidity of pancreatic surgery have decreased
      to acceptable levels, the complex question arises whether pancreatic resection
      should be performed in patients with preoperatively doubtful resectable
      pancreatic cancer. METHODS: Perioperative parameters and outcome of 80 patients
      who underwent a microscopically incomplete (R1) resection were compared with
      those of 90 patients who underwent a bypass for locally advanced disease for
      pancreatic adenocarcinoma. All patients initially underwent exploratory
      laparotomy with the intention to perform a resection. Quality of life was
      assessed by analyzing readmissions and their indications. RESULTS: Groups were
      similar with respect to age, presenting symptoms, and preoperative health status.
      Tumors were significantly larger in the bypass group (3.5 cm vs 2.9 cm, P < .01).
      Hospital mortality was comparable: zero after R1 resection and 2% after bypass.
      Of all severe complications, only intra-abdominal hemorrhage occurred
      significantly more frequently after resection (10% vs 2%; P = .03). Hospital stay
      after resection was significantly longer than after bypass (16 vs 10 days; P <
      .01). Survival was significantly longer after R1 resection (15.8 vs 9.5 months, P
      < .01). Sixty-one percent of patients were readmitted for a total of 215
      admissions, equally distributed between groups. After R1 resection, 0.58% of the
      total survival time after initial discharge was spent in the hospital, after
      bypass, 0.69%, which was not significantly different. CONCLUSIONS: R1 pancreatic
      resection and bypass for locally advanced disease can be performed with
      comparable low mortality and morbidity rates. Readmission rates are also
      comparable between groups and time spent in the hospital after initial discharge
      is low. Because resection offers adequate palliation in pancreatic cancer, a more
      aggressive surgical approach in patients who are found to have a doubtfully
      resectable tumor could be advocated, even if only an R1 resection can be
      achieved.

PMID- 16455328
TI  - Calcitonin gene-related peptide partially mediates nociception in acute
      experimental pancreatitis.
AB  - BACKGROUND: The mechanism by which pancreatitis causes pain is unknown. The
      neuropeptide calcitonin gene-related peptide (CGRP) is released after sensory
      nerve activation and promotes nociceptive signaling in models of visceral pain.
      We hypothesized that acute pancreatitis leads to the activation of pancreatic
      sensory neurons that release CGRP in the dorsal horn of the spinal cord. This
      signal is ultimately transmitted to the brain, and pain is sensed. METHODS: To
      induce pancreatitis, rats were injected with l-arginine (500 mg/kg)
      intraperitoneally or saline (control). Pancreatitis was confirmed by measuring
      serum amylase and evaluating pancreatic histology. Activation of nociceptive
      pathways was evaluated by counting Fos-like immunoreactive nuclei (FLI) in the
      dorsal horn of the spinal cord at T3-L1. Some animals received the CGRP
      antagonist CGRP(8-37) (50 microg intrathecally) 2 hours before perfusion. Animals
      were compared using a 2-tailed t test. RESULTS: l-Arginine treatment induced
      acute necrotizing pancreatitis in the rat at 24 hours. l-Arginine (24 hours)
      increased FLI in the dorsal horn of the spinal cord, with a peak effect at L1.
      Intrathecal administration of CGRP(8-37) significantly decreased the number of
      FLI nuclei in the dorsal horn of the spinal cord in T11-L1. CONCLUSIONS:
      Nociception in the l-arginine model of acute pancreatitis is partially mediated
      by the release of CGRP in the dorsal horn of the spinal cord. Antagonism of CGRP
      or its receptors may be useful in treating pain from acute pancreatitis.

PMID- 16455329
TI  - Omega-3 fatty acids improve appetite in cancer anorexia, but tumor resecting
      restores it.
AB  - BACKGROUND: Tumor growth leads to cancer anorexia that is ameliorated using omega
      3 fatty acids (omega-3FA). We hypothesize that omega-3FA modulates up-regulation
      of hypothalamic orexigenic neuropeptide Y (NPY) and down-regulation of
      anorexigenic alpha melanocyte-stimulating hormone (alpha-MSH) and serotonin 1B
      receptors (5-HT(1B)-receptors) in tumor-bearing rats. METHODS: Twenty-eight tumor
      bearing rats were fed either chow (TB-Control) or omega-3FA (TB-omega-3FA). When
      anorexia developed in TB-Control rats, they and a cohort of TB-omega-pi-3 rats
      were killed. The rest had their tumor resected (R-Control and R-omega-3FA), and
      when anorexic TB-Controls normalized their food intake, brains were removed for
      hypothalamic immunocytochemical study of NPY, alpha-MSH, and 5-HT(1B)-receptor
      antibodies concentrations. Comparison among slides were assessed by image
      analysis and analyzed by ANOVA and t test. RESULTS: At anorexia, hypothalamic NPY
      in arcuate nucleus (ARC) increased by 38% in TB-omega3FA versus TB-Control,
      whereas alpha-MSH decreased 64% in ARC and 29% in paraventricular nucleus (PVN).
      Omega-3FA diet in anorexia (TB-omega-3FA vs R-omega-3FA) produced similar
      qualitative changes of NPY (22% increase) and alpha-MSH (31% decrease) in ARC,
      with concomitant decrease of 37% in 5-HT(1B)-receptors in PVN, confirming the
      influence of omega-3FA on the hypothalamic food intake modulators. However, after
      tumor resection (TB-Control vs R-Control) a 97% increase in NPY and a 62%
      decrease in alpha-MSH occurred that was significantly greater than in rats fed
      omega-3FA diet. CONCLUSION: Tumor resection and omega-3FA modifies hypothalamic
      food intake activity, up-regulating NPY and down-regulating alpha-MSH and 5
      HT(1B)-receptors. Tumor resection in anorexic rats on chow diet restored
      hypothalamic NPY, alpha-MSH, and food intake quantitatively more than in rats fed
      omega3FA diet.

PMID- 16455330
TI  - Does vagal nerve stimulation affect body composition and metabolism? Experimental
      study of a new potential technique in bariatric surgery.
AB  - BACKGROUND: It has been shown that vagal nerve stimulation (VNS) can affect body
      mass. The aim of this study was to evaluate effect of VNS on body mass, body
      composition, metabolic rate, and plasma leptin and IGF-I levels. METHODS: Eight
      female pigs were included in the study. Under general anesthesia, a bipolar
      electrode was implanted on the anterior vagal nerve by laparoscopy. Group A was
      treated by VNS, and group B was the control. After 4 weeks, stimulation was
      discontinued in group A and started in group B. The following parameters were
      evaluated: body mass, body composition, metabolic rate, plasma leptin and IGF-1
      levels and intramuscular fat content (IMF). RESULTS: VNS attenuated body weight
      gain (2.28 +/- 3.47 kg vs 14.04 +/- 6.75 kg; P = .0112, for stimulation and
      nonstimulation periods, respectively), backfat gain (0.04 +/- 0.26 mm vs 2.31 +/-
      1.12 mm) and IMF gain (-3.76 +/- 6.06 mg/g MS vs 7.24 +/- 12.90 mg/g MS; P =
      .0281). VNS resulted in lower backfat depth/loin muscle area ratio (0.33 +/-
      0.017 vs 0.38 +/- 0.35; P = .0476). Lower plasma IGF-I concentration was found
      after VNS (-3.67 +/- -11.55 ng/mL vs 9.86 +/- 10.74 ng/mL; P = .0312). No
      significant changes in other parameters were observed. CONCLUSIONS: VNS affects
      body weight mainly at the expense of body fat resources; however, metabolic rate
      is not affected.

PMID- 16455331
TI  - Minimally invasive sentinel lymph node mapping of the pig colon with Lymphoseek.
AB  - BACKGROUND: Minimally invasive surgery and sentinel node mapping are being
      utilized increasingly in colon cancer surgery. Making these techniques efficient
      and easy to perform will be essential for the future of this and other
      gastrointestinal operations. The purpose of this study was to test a new
      laparoscopic gamma detection probe for minimally invasive sentinel node mapping
      of the colon, while utilizing Lymphoseek, a radiopharmaceutical specifically
      designed for sentinel lymph node (SLN) detection. METHODS: Eight anesthetized
      pigs received an endoscopic co-injection of Lymphoseek and Isosulfan Blue in the
      colon. The laparoscopic gamma detector, inserted via a 12-mm trocar, was used to
      identify radioactive sentinel lymph nodes. The reliability of the side-viewing
      probe was tested using a radioactive source. All blue and radioactive lymph nodes
      were excised and the signal-to-background ratio (S/B) and percent of injected
      dose (%ID) were measured. RESULTS: The probe was easy to maneuver and led to
      efficient visualization of the radioactive node. The side port allowed for better
      distinction between injection site scatter and sentinel node activity. The
      reliability of the probe was validated by an identification rate of 97%. At least
      one SLN was detected for each pig; two SLNs were detected in two pigs. All SLNs
      were stained blue. The SLN S/B ranged from 38 to 315 and the %ID ranged from
      0.06% to 2.01%. Sentinel nodes were found within 10 minutes. CONCLUSIONS:
      Minimally invasive sentinel node mapping with the radiopharmaceutical Lymphoseek
      and a side-viewing gamma detector yielded high S/B and directionality for
      accurate mapping of gastrointestinal sentinel lymph nodes within minutes of
      radiotracer administration.

PMID- 16455332
TI  - CT lymphography-navigated sentinel lymph node biopsy in patients with superficial
      esophageal cancer.
AB  - BACKGROUND: To evaluate experimentally and clinically the feasibility of a newly
      developed technique of endoscopic computed tomography (CT) lymphography with
      endoscopic submucosal injection of iopamidol for esophageal sentinel lymph node
      (SLN) mapping and biopsy examination. METHODS: Nine anesthetized dogs underwent
      CT after endoscopic submucosal injection of 2 mL iopamidol; 1.25-mm thick CT
      images were obtained before and at 1, 3, 5, 7, and 10 minutes after contrast
      injection. Clinically, 12 patients with superficial esophageal cancer
      (preoperative imaging stage: cT1, cN0) underwent CT lymphography in a similar
      fashion at 1, 5, and 10 minutes after peritumoral injection, followed by radical
      esophagectomy and regional lymph node dissection under CT lymphography guidance.
      RESULTS: CT lymphography visualized the draining lymphatic vessels and SLNs
      within 5 minutes after contrast injection. All 14 SLNs in dogs (average, 1.5
      nodes per animal; range, 1-2) and 28 SLNs in patients (average, 2.3 nodes per
      patient; range, 1-4) were found intraoperatively at the correct location under CT
      lymphography guidance. Lymph node metastasis could be detected with excellent
      sensitivity and accuracy in this small number of patients with no false-negative
      findings; metastasis was positive only in the preoperatively identified SLNs in 4
      patients and in both SLNs and distant nodes in 1 patient, and was negative in all
      resected nodes in the remaining 7 patients. CONCLUSIONS: Endoscopic CT
      lymphography appears to allow accurate identification of direction and locations
      of lymph flow and SLNs, and has the potential clinical applicability for
      esophageal SLN mapping and biopsy examination, but will require a large study to
      determine its accuracy and usefulness.

PMID- 16455334
TI  - Hypoxia/reoxygenation impairs glucose absorption and cAMP-mediated secretion more
      profoundly than glutamine absorption and Ca2+/PKC-mediated secretion in rat ileum
      in vitro.
AB  - BACKGROUND: Intestinal ischemia and reperfusion may lead to profuse secretion of
      water and electrolytes. The underlying mechanisms have been related to increased
      hydrostatic pressure, to denudation of intestinal villi, and, recently, to
      adenosine-mediated enhancement of chloride secretion. METHODS: We studied the
      effects of hypoxia and reoxygenation on baseline electrophysiologic parameters;
      on glucose- and glutamine-induced absorption; on secretion induced by carbachol,
      histamine, and forskolin; and on epithelial barrier function to disodium
      fluorescein and horseradish peroxidase in rat ileum mounted in Ussing chambers.
      RESULTS: We observed that 30 minutes of hypoxia followed by 60 minutes of
      reoxygenation differentially affected glucose and glutamine absorption to 11% and
      42%, respectively, of control values. Cyclic adenosine monophosphate-mediated
      secretion induced by forskolin was reduced to 9% of controls. In contrast,
      Ca(2+)/protein kinase C-mediated secretion induced by carbachol or histamine was
      reduced only to 35% to 48% of controls. Furthermore, the epithelium fully was
      capable of maintaining its barrier function to small and large permeability
      probes, even after 90 minutes of hypoxia. CONCLUSIONS: We conclude that hypoxia
      and reoxygenation differentially impair nutrient absorption, corroborating recent
      absorption data in in vivo models of ischemia, and that it differentially affects
      secretory capacity in crypts, dependent on the intracellular messenger pathway.
      The relative persistence of Ca(2+)/protein kinase C-mediated secretion to hypoxia
      and reoxygenation indicates that secretagogues that activate this pathway play a
      significant role in the intraluminal fluid sequestration and diarrhea observed
      after intestinal ischemia and reperfusion.

PMID- 16455333
TI  - Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid
      peptides that bind to pathogenic IgM.
AB  - BACKGROUND: The injury sustained by reperfused skeletal muscle is inflammatory
      and is initiated by binding of pre-formed IgM to involved tissue, followed by
      local complement activation and further inflammation. A clone of natural IgM has
      been described that initiates this injury, suggesting that specific antigens are
      exposed on ischemic tissues that act as ligands for this pathogenic antibody. In
      these experiments, we examine the properties of short peptide sequences, and
      their homologues, that bind to the antigen-combining site of this pathogenic IgM
      clone. METHODS: A 12-mer phage display library was biopanned with the pathogenic
      IgM clone and then negatively selected against an inactive natural IgM clone. All
      8 clones that bound specifically to the pathogenic IgM had closely related amino
      acid sequences. P8 is the clone that bound most avidly. Tissue lysates from
      ischemic tissue were reacted with pathogenic IgM, and immune complexes isolated
      and analyzed on SDS-PAGE. Bands were excised and sequenced, identifying non
      muscle myosin as the protein reacting with pathogenic antibody in ischemic gut
      and glycogen phosphorylase as the counterpart in ischemic skeletal muscle. Both
      proteins contain sequence homologous to P8; N2 and GP1 are the natural 12-mers
      homologues that are contained within non-muscle myosin and glycogen
      phosphorylase, respectively. Wild-type C57/Bl6 mice, divided into groups
      receiving saline, P8, N2, GP1, or a random peptide at the start of the
      experiment, were subjected to 2 hours of tourniquet induced hind limb ischemia
      and 3 hours of reperfusion. Muscle was assessed for injury with histology and for
      immune activation with histochemistry. RESULTS: Intravenous administration of P8,
      N2, and GP1 led to significant attenuation of muscle injury (13 +/- 1.8 injured
      fibers/50 counted, 12 +/- 0.81, 8.0 +/- 0.73 respectively) after reperfusion
      injury compared to animals receiving saline (26 +/- 2.3) or the same mass of a
      random peptide (22 +/- 2.3), P less than .05. This level of protection from
      injury is comparable to that seen in the absence of antibody altogether. As well,
      P8-treated animals exhibited a marked decrease in deposition of IgM (as well as
      C3) in comparison to saline treated controls. CONCLUSIONS: Specific peptide
      blockade of an injury-inducing IgM clone decreased the local consequences of
      skeletal muscle ischemia/reperfusion injury in wild-type animals that have the
      full repertoire of IgM specificities. This indicates that the antibodies that
      initiate reperfusion injury have specificity only for P8-related antigens. This
      could also indicate that the variety of relevant ischemic antigens is quite
      restricted.

PMID- 16455335
TI  - Mechanisms of c-reactive protein up-regulation in arterialized vein grafts.
AB  - BACKGROUND: C-reactive protein (CRP), an acute phase reactant, is an independent
      predictor of coronary artery syndromes and a mediator of the vascular response to
      injury. CRP has been found in arterialized vein grafts and has been linked to
      atherogenesis; however, its involvement in vein graft early failure or intimal
      hyperplasia has not been assessed. This study was designed to investigate the
      mechanism(s) of CRP up-regulation in arterialized vein grafts. METHODS: Carotid
      artery bypass with arterialized jugular vein grafts (AVG) was performed in 18
      dogs. AVG were harvested at 3, 8, and 24 hours and 4, 14, and 28 days, using the
      femoral vein obtained at the time of AVG harvest as a control. Serum CRP levels
      were characterized by enzyme-linked immunosorbent assay; AVG expression of CRP
      was studied by immunofluorescence, Western blotting, in situ hybridization,
      Northern blotting, and quantitative RT-PCR. RESULTS: CRP levels peaked at 24
      hours in serum and AVG but remained at baseline in control veins. By double
      immunofluorescence, CRP was associated with the media and adventitia of AVG.
      However, Northern blotting analysis showed no CRP mRNA expression in AVG. Reverse
      transcriptase polymerase chain reaction analysis confirmed the lack of up
      regulation of CRP in AVG. CONCLUSION: CRP levels are increased in AVG, peaking 24
      hours after arterialization. However, no significant production of CRP was
      detected in AVG. Therefore, increased CRP levels within AVG appear to originate
      mostly from CRP diffusion from the systemic circulation. These results have
      significant implications for the development of strategies aimed at blocking CRP
      up-regulation in bypass grafts.

PMID- 16455336
TI  - Outcome after hepatic resection versus combined resection and microwave ablation
      for multiple bilobar colorectal metastases to the liver.
AB  - BACKGROUND: We investigated the efficacy of microwave ablation plus hepatectomy
      for multiple bilobar colorectal metastases to the liver. No consensus exists
      concerning local ablation plus hepatic resection for treating multiple bilobar
      colorectal liver metastases, partly because of a lack of long-term comparative
      survival data. METHODS: Clinicopathologic data were analyzed retrospectively for
      53 consecutive patients with 5 or more bilobar liver metastases from colorectal
      cancer who underwent hepatectomy with or without microwave ablation. Outcome
      measures were recurrence rate, recurrence pattern, and survival. RESULTS:
      Combined resection/ablation was performed more frequently in patients with more
      liver metastases (P = .03). No significant differences were found for overall,
      disease-free, or hepatic recurrence-free survival between 16 patients with
      resection/ablation and 37 patients with resection (P = .43, .54, and .86,
      respectively). Multivariate analysis selected prehepatectomy carcinoembryonic
      antigen concentration in serum as an independent prognosticator for survival (P =
      .02), but not resection/ablation versus resection. In patients with combined
      resection/ablation, recurrence occurred near the resection or ablation line in
      only 2 patient (22%), whereas multiple neoplasms (>/=4) was the most common liver
      recurrence pattern (78%). CONCLUSIONS: Microwave ablation plus hepatic resection
      expanded indications for operation to treat multiple bilobar liver metastases,
      with survival similar to that in less-involved hepatic resection patients.

PMID- 16455337
TI  - Why volunteer to go back to the Middle East?

PMID- 16455339
TI  - Giant sigmoid diverticulum.

PMID- 16455340
TI  - Preface to the 2006 Mini-Primer on Allergic and Immunologic Diseases.

PMID- 16455341
TI  - 1. Overview of the human immune response.
AB  - The human immune system mobilizes a broad repertoire of innate and adaptive
      responses to protect against the universe of pathogens it encounters. Central to
      these protective responses are its mechanisms to distinguish self from nonself.
      This overview describes the major mechanisms used by the immune system to respond
      to invading microbes and identifies settings in which disturbed immune function
      exacerbates tissue injury.

PMID- 16455342
TI  - 2. Update on primary immunodeficiency diseases.
AB  - The pace of discovery in primary immunodeficiency continues to accelerate. In
      particular, lymphocyte defects have been the source of the most impressive
      expansion in recent years. Novel forms of agammaglobulinemia, class-switch
      defects, and T-B(+) severe combined immunodeficiency have been described. Little
      by little, the genetic heterogeneity of the common variable immunodeficiency and
      IgA deficiency phenotypes continues to be unraveled as new molecular defects have
      been reported in these patients as well. The phenotypic spectrum of DiGeorge
      syndrome has been further developed, along with promising advances in therapy.
      Defects of nuclear factor kappaB regulation and Toll-like receptor signaling have
      been described, along with defects of chemokine receptors and cytoplasmic
      proteases. Clinically defined immunodeficiencies, such as hyper-IgE syndrome and
      idiopathic CD4 lymphocytopenia, are also discussed. Finally, significant adverse
      effects in some patients have tempered initial enthusiasm for gene therapy.

PMID- 16455343
TI  - 3. Cytokines and chemokines.
AB  - Cytokines and chemokines are secreted proteins with growth, differentiation, and
      activation functions that regulate the nature of immune responses. Cytokines are
      involved in nearly every facet of immunity and inflammation, from induction of
      the innate immune response to the generation of cytotoxic T cells and the
      development of antibodies by the humoral immune system. The combination of
      cytokines that are produced in response to an immune insult determines which arm
      of the immune system will be activated. For this update, recent advances in our
      understanding of cytokines will be discussed, which includes the IL-10, IL-17,
      and IL-27 families.

PMID- 16455344
TI  - 4. Autoimmunity, vasculitis, and autoantibodies.
AB  - Autoimmune diseases are distinct clinical syndromes characterized by various
      alterations in normal immune responsiveness, such that there is a loss of
      tolerance to particular host constituents. In most cases, despite years of
      intense investigation, the etiopathogenic antigens initiating these systemic
      inflammatory conditions remain undefined. However, a great deal has been learned
      about the changes in components of the immune response relevant to the
      propagation and sustenance of these often chronic disorders. In addition, various
      hormonal, environmental, physiologic, and other influences that affect their
      expression have been identified. The expression and ultimate clinical outcome of
      autoimmune diseases usually relate to inflammation-related damage to the target
      organ with subsequent dysfunction. Certain immune conditions, such as autoimmune
      thyroid disease, largely affect a single organ, whereas others, such as systemic
      lupus erythematosus, heterogeneously affect sundry organ systems. Autoantibodies
      directed against normal host antigens are a common feature of many autoimmune
      diseases. In some cases they are pathogenic, whereas in others they serve as
      markers for organ involvement or outcomes. Clinical descriptions of autoimmune
      diseases date back many decades in some cases. Recent efforts at formulating
      classification criteria have allowed clearer distinctions and more accurate
      stratification. Greater understanding of the immunopathogenesis of autoimmune
      conditions has led to the development and introduction into the clinic of novel
      immunomodulatory therapies and treatment paradigms that have substantially
      improved the outcomes for patients affected by these serious conditions.

PMID- 16455345
TI  - 5. IgE, mast cells, basophils, and eosinophils.
AB  - IgE, mast cells, basophils, and eosinophils constitute essential elements in
      allergic inflammation. Allergen-specific IgE, synthesized in response to
      allergens in the environment, becomes fixed to FcepsilonRI on the membranes of
      mast cells and basophils. Aggregation of receptor-bound IgE molecules on re
      exposure to specific allergen results in the production of mediators that produce
      the allergic response. Principal among the cells drawn to sites of mediator
      release is the eosinophil.

PMID- 16455346
TI  - 6. Asthma: Factors underlying inception, exacerbation, and disease progression.
AB  - Asthma is a heterogeneous disorder that is characterized by variable airflow
      obstruction, airway inflammation and hyperresponsiveness, and reversibility
      either spontaneously or as a result of treatment. Multiple causes no doubt exist
      for both its inception and symptom exacerbation once the disease is established.
      Factors underlying inception can range from viral respiratory tract infections in
      infancy to occupational exposures in adults. Factors underlying asthma
      exacerbations include allergen exposure in sensitized individuals, viral
      infections, exercise, irritants, and ingestion of nonsteroidal anti-inflammatory
      agents among others. Exacerbating factors might include one or all of these
      exposures and vary both among and within patients. Asthma treatment is determined
      to a large extent after an assessment of severity, which can be variable over
      time and assessed in 2 domains: impairment (current) and risk (long-term
      consequences). Unfortunately, despite the availability of effective therapies,
      suboptimal asthma control exists in many patients on a worldwide basis. The
      future development of novel therapies and treatment paradigms should address
      these disparities.

PMID- 16455347
TI  - 7. Control of allergic airway inflammation through immunomodulation.
AB  - Among the asthma clinical trials published over the last several years, a unique
      subset has focused on novel means for inhibiting the airway inflammation that is
      believed to cause airway obstruction in many patients. Such interventions,
      broadly considered here as immune-modifying or immunomodulatory therapies,
      include several new drugs (omalizumab, suplatast tosilate, anti-cytokine
      antibodies, soluble receptors, and recombinant cytokines) and bacterial extracts.
      In this chapter we review the major findings with these clinical trials and
      indicate which have changed the management of asthma, which have not, and those
      that deserve further study.

PMID- 16455348
TI  - 8. Drug allergy.
AB  - Drug reactions can be considered as being either predictable or unpredictable. A
      predictable reaction would be the result of the pharmacologic action of the
      medication. An unpredictable reaction might be idiosyncratic, might be drug
      intolerance, or might have or imply an immunologic basis, such as being IgE
      mediated. Immediate reactions that are not IgE mediated can be considered as
      pseudoallergic (non-IgE-mediated mast cell activation). This review will discuss
      allergic and immunologic reactions to immunomodulators, penicillins and
      cephalosporins, sulfonamides, aspirin, and nonselective nonsteroidal anti
      inflammatory drugs and consider the serious drug-related conditions of Stevens
      Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The field of drug
      "allergy" has expanded to include adverse reactions associated with
      immunosuppressive medications, anticytokine therapies, and mAbs. The cytokine
      release reaction that occurs with anti-CD20 antibody infusions in patients with
      leukemia and white blood cell counts of greater than 50 x 10(9)/L is associated
      with high concentrations of TNF, IL-6, and IL-8. Because of the findings of
      fever, dyspnea, rigors, and hypotension, this reaction resembles the Jarisch
      Herxheimer reaction that occurs 60 to 90 minutes after penicillin administration
      in patients with secondary syphilis. Furthermore, the care of the patient with
      penicillin allergy has been made more difficult in the absence of the major
      determinant, penicilloyl-polylysine, in that from 34% to 84% of patients who have
      positive skin test reactions to penicillin have exclusively positive reactions to
      the major determinant. SJS and TEN typically are caused by medications within 1
      to 8 weeks of initiation of therapy. Evidence for death of the keratinocytes
      through (1) drug-specific cytotoxicity with the perforin-granzyme B-mediated
      killing and (2) activation of Fas on keratinocytes have provided explanations for
      the sloughing of skin. Unfortunately, intravenous immunoglobulin therapy for SJS
      and TEN has been disappointing.

PMID- 16455349
TI  - 9. Food allergy.
AB  - Food allergy, defined as an adverse immune response to food proteins, affects as
      many as 6% of young children and 3% to 4% of adults. Food-induced allergic
      reactions are responsible for a variety of symptoms involving the skin,
      gastrointestinal tract, and respiratory tract and might be caused by IgE-mediated
      and non-IgE-mediated (cellular) mechanisms. Our understanding of how food allergy
      represents an abrogation of normal oral tolerance is evolving. Although any food
      can provoke a reaction, relatively few foods are responsible for the vast
      majority of significant food-induced allergic reactions: milk, egg, peanuts, tree
      nuts, fish, and shellfish. A systematic approach to diagnosis includes a careful
      history, followed by laboratory studies, elimination diets, and often food
      challenges to confirm a diagnosis. Many food allergens have been characterized at
      a molecular level, which has increased our understanding of the
      immunopathogenesis of food allergy and might soon lead to novel diagnostic and
      therapeutic approaches. Currently, management of food allergies consists of
      educating the patient to avoid ingesting the responsible allergen and to initiate
      therapy in case of an unintended ingestion.

PMID- 16455350
TI  - 10. Atopic dermatitis.
AB  - Atopic dermatitis is a common chronic inflammatory skin disease often preceding
      the development of asthma and allergic disorders, such as food allergy or
      allergic rhinoconjunctivitis. Pathophysiology involves a complex series of
      interactions between resident and infiltrating cells orchestrated by
      proinflammatory cytokines and chemokines. A deficiency of antimicrobial peptides
      might contribute to the propensity for colonization or infection by microbial
      organisms seen in atopic dermatitis. New treatment approaches include use of
      topical steroids as maintenance therapy and use of topical calcineurin inhibitors
      for early intervention with topical steroids used as rescue therapy.

PMID- 16455351
TI  - Preferential inhibition of the lycopene epsilon-cyclase by the substituted
      triethylamine compound MPTA in higher plants.
AB  - In addition to the usual complement of carotenoids found in the plant leaf
      tissues, lettuce (Lactuca sativa), unusually, possesses large amounts of the diol
      lactucaxanthin. This carotenoid possesses two epsilon-end-groups and its presence
      provides a good model in which to study the effects of the substituted
      triethylamine compound 2-(4-methylphenoxy)triethylamine (MPTA) on the cyclisation
      of beta- and epsilon-end-groups during the biosynthesis of carotenoids. Treatment
      with 10 or 20microM MPTA significantly reduced levels of both beta-carotene and
      neoxanthin (up to 18-fold), whilst levels of violaxanthin and lutein were less
      affected (4-fold reduction). In contrast, levels of lactucaxanthin were not
      reduced even at the highest inhibitor concentration, and at 10microM MPTA levels
      of this xanthophyll doubled. The pigment stoichiometry of the bulk light
      harvesting complex (LHCIIb) isolated from treated plants shows that
      lactucaxanthin successfully substituted for lutein and neoxanthin in two of the
      xanthophyll binding sites, namely L2 and N1. Inhibition of cyclisation was
      accompanied by the accumulation of lycopene and trace amounts of delta-carotene
      and a number of oxygenated derivatives of these precursors. Two forms of mono
      hydroxy lycopene were identified together with mono-epoxy delta-carotene.

PMID- 16455352
TI  - Effect of water stress on proline accumulation of genetically modified potatoes
      (Solanum tuberosum L.) generating fructans.
AB  - This study aimed to investigate the effect of water stress on the accumulation of
      proline in the leaves of transgenic potato lines generating fructans. The results
      of the series of bifactorial experiments in 2002 and 2003 indicated an increase
      of the proline level in leaves of all potato lines examined under water deficit.
      In addition, an increase in proline concentration during plant development was
      observed. The proline content was related to leaf water potential and relative
      water content (RWC), which indicates that proline could be involved in
      osmoregulation of potato plants under the experimental conditions. Surprisingly,
      under water deficit, the proline level was lowest in most of the transgenic
      SST/FFT-lines, which generate fructan molecules with a high degree of
      polymerization. Therefore, a pleiotropic effect can not be excluded as the reason
      for the divergence in behavior of these transgenic lines. The present results
      suggest that the modification of carbohydrate metabolism, especially the high
      content of soluble carbohydrates, may affect water stress-induced proline
      accumulation.

PMID- 16455353
TI  - Inhibitory role of gibberellins in theobroxide-induced flowering of Pharbitis
      nil.
AB  - Theobroxide, a novel active compound isolated from a fungus, has been reported
      previously to induce potato tuberization and flower bud formation in Pharbitis
      nil under non-inductive long-day conditions. Up to date, the action mechanism of
      theobroxide on flower-bud induction of P. nil, however, is still unknown. In the
      present study, we observed a reduction of the stem length, along with the
      induction of flower buds, in theobroxide-treated and short-day-grown P. nil
      plants. Also, the results showed that flower bud formation was delayed markedly
      in P. nil seedlings with removal of cotyledons or exposure to night break. The
      suppression effect of night-break and cotyledon-removal, however, was abolished
      completely by spraying theobroxide. Endogenous gibberellin(1/3) contents in P.
      nil plants treated with theobroxide or grown under short-day conditions were
      relatively lower, suggesting that gibberellins probably are negatively involved
      in theobroxide- and short-day-induced flower-bud formation of P. nil.

PMID- 16455354
TI  - Contributions of PIP(2)-specific-phospholipase C and free salicylic acid to heat
      acclimation-induced thermotolerance in pea leaves.
AB  - The relationship between the accumulation in endogenous free salicylic acid (SA)
      induced by heat acclimation (37 degrees C) and the activity of PIP(2)
      phospholipase C (PIP(2)-PLC; EC 3.1.4.3) in the plasma membrane fraction was
      investigated in pea (Pisum sativum L.) leaves. We focused our attention on the
      hypothesis that positive SA signals induced by heat acclimation may be relayed by
      PIP(2)-PLC. Heat acclimation induced an abrupt elevation of free SA preceding the
      activation of PLC toward PIP(2). Immunoblotting indicated a molecular mass with
      66.5kDa PLC plays key role in the development of thermotolerance in pea leaves.
      In addition, some characterizations of PLC toward PIP(2) isolated from pea leaves
      with two-phase purification containing calcium concentration, pH and a protein
      concentration were also studied. Neomycin sulfate, a well-known PIP(2)-PLC
      inhibitor, was employed to access the involvement of PIP(2)-PLC in the
      acquisition of heat acclimation induced-thermotolerance. We were able to identify
      a PIP(2)-PLC, which was similar to a conventional PIP(2)-PLC in higher plants,
      from pea leaves suggesting that PIP(2)-PLC was involved in the signal pathway
      that leads to the acquisition of heat acclimation induced-thermotolerance. On the
      basis of these results, we conclude that the involvement of free SA may function
      as the upstream event in the stimulation of PIP(2)-PLC in response to heat
      acclimation treatment.

PMID- 16455355
TI  - Arbuscular mycorrhizal fungi influence growth, osmotic adjustment and
      photosynthesis of citrus under well-watered and water stress conditions.
AB  - The influence of arbuscular mycorrhizal (AM) fungus Glomus versiforme on plant
      growth, osmotic adjustment and photosynthesis of tangerine (Citrus tangerine)
      were studied in potted culture under well-watered and water stress conditions.
      Seven-day-old seedlings of tangerine were transferred to pots containing Glomus
      versiforme or non-AMF. After 97 days, half of the seedlings were subject to water
      stress and the rest were well-watered for 80 days. AM colonization significantly
      stimulated plant growth and biomass regardless of water status. The soluble sugar
      of leaves and roots, the soluble starch of leaves, the total non-structural
      carbohydrates (NSC) of leaves and roots, and the Mg(2+) of leaves were higher in
      AM seedlings than those in corresponding non-AM seedlings. The levels of K(+) and
      Ca(2+) in leaves and roots were higher in AM seedlings than those in non-AM
      seedlings, but differences were only significant under water stress conditions.
      Moreover, AM colonization increased the distributed proportions of soluble sugar
      and NSC to roots. However, the proline was lower in AM seedlings compared with
      that in non-AM seedlings. AM seedlings had higher leaf water potential (Psi),
      transpiration rates (E), photosynthetic rates (Pn), stomatal conductance (g(s)),
      relative water content (RWC), and lower leaf temperature (Lt) than corresponding
      non-AM seedlings. This research also suggested that AM colonization improved the
      osmotic adjustment originating not from proline but from NSC, K(+), Ca(2+) and
      Mg(2+), resulting in the enhancement of drought tolerance.

PMID- 16455356
TI  - Isolation of a cotton reversibly glycosylated polypeptide (GhRGP1) promoter and
      its expression activity in transgenic tobacco.
AB  - Reversibly glycosylated polypeptides (RGPs) are thought to be involved in
      polysaccharide metabolism. A cDNA of the cotton (Gossypium hirsutum) RGP gene,
      designated GhRGP1, has previously been characterized, and is preferentially
      expressed in fiber cells. In order to investigate its temporal and spatial
      control, we isolated a 624bp fragment upstream of the GhRGP1 coding sequence
      using a polymerase chain reaction (PCR)-based genomic walking method,
      transcriptionally fused the 624bp promoter sequence to the beta-glucuronidase
      (GUS) gene, and analyzed the stable gene expression in tobacco (Nicotiana
      tabacum). In 4-week-old transgenic tobacco plants, the highest expression level
      was observed in roots, and the GUS activity was 1.13- and 6.65-fold higher than
      that in stems and leaves, respectively. In the reproductive growth stage, the GUS
      expression level was highest in the pistils and the GUS activity in the stigmas
      and styles were 17.6-fold higher than that in the ovaries. High GUS activity was
      also detected in the anthers. In addition, histochemical staining for GUS
      activity on transgenic tobacco plants further indicated a higher expression in
      the trichomes, seeds and vascular tissues of stems. Abiotic stress treatments on
      transgenic tobacco plants showed that wounding and dehydration induced GUS
      expression. These results demonstrated the spatial and temporal regulation of a
      cotton RGP promoter in a model plant, and provided an important insight into the
      factors that control the fiber development and stress responses of the gene.

PMID- 16455357
TI  - A putative CENTRORADIALIS/TERMINAL FLOWER 1-like gene, Ljcen1, plays a role in
      phase transition in Lotus japonicus.
AB  - CENTRORADIALIS/TERMINAL FLOWER 1 (CEN/TFL1) genes play an important role in the
      phase transition of plant flowering. Here we characterized the expression pattern
      of a CEN/TFL1-like gene, Ljcen1, from Lotus japonicus. Sequence analysis revealed
      that Ljcen1 shared 67-76% identity to its homologs from a variety of plant
      species. Ljcen1 transcripts could be detected at the young root tip and
      reproductive shoot apical meristem of L. japonicus. RNA in situ hybridization
      analysis revealed that Ljcen1 was continuously expressed in the sub-domain of the
      primary inflorescence meristem and transiently expressed in the secondary
      inflorescence meristem. The ectopic expression of Ljcen1 in Arabidopsis driven by
      double CaMV 35S promoter delayed the flowering. These results suggested that
      Ljcen1 gene was involved in a conserved CEN/TFL1 pathway that functions in phase
      transition of shoot apical meristem in L. japonicus.

PMID- 16455358
TI  - Computational identification and systematic analysis of the ACR gene family in
      Oryza sativa.
AB  - Based on sequence similarity search and domain detection, nine ACT domain repeat
      protein-coding genes (the "ACR" genes) in rice were identified, which were mainly
      distributed on the chromosomes 2, 3, 4, and 8. An InterPro database search
      indicated that four copies of the ACT domain linearly occupied the entire
      polypeptide. The first three ACT domains were linked by two different sequences.
      However, the fourth ACT domain was extremely close to ACT3. Gene structure
      comparisons showed large differences in exon numbers, from three to eight, among
      members of the rice ACR gene family. In addition, it appeared that gene
      duplication might be operative when the compositions of exons and introns were
      analyzed. Phylogenetic analysis divided the ACR gene family into five distinct
      groups, and this division was generally according to the expression patterns of
      the ACR genes. The Arabidopsis and rice ACR proteins were clustered across
      together, suggesting that these ACR genes might originate from an ancient common
      ancestor. Notably, the identification of orthologues and paralogues would be
      useful for rice gene functional annotation.

PMID- 16455359
TI  - cDNA-AFLP analysis of seed germination in Arabidopsis thaliana identifies
      transposons and new genomic sequences.
AB  - A cDNA-AFLP experiment was designed to identify and clone nucleotide sequences
      induced during seed germination in Arabidopsis thaliana. Sequences corresponding
      to known genes involved in processes important for germination, such as
      mitochondrial biogenesis, protein synthesis and cell cycle progression, were
      isolated. Other sequences correspond to Arabidopsis BAC clones in regions where
      genes have not been annotated. Notably, a number of the sequences cloned did not
      correspond to available sequences in the databases from the Arabidopsis genome,
      but instead present significant similarity with DNA from other organisms, for
      example fish species; among them, some may encode transposons. A number of the
      sequences isolated showed no significant similarity with any sequences in the
      public databases. Oligonucleotides derived from these new sequences were used to
      amplify genomic DNA of Arabidopsis. Expression analysis of representative
      sequences is presented. This work suggests that, during germination, there may be
      a massive transposon mobilization that may be useful in the annotation of new
      genome sequences and identification of regulatory mechanisms.

PMID- 16455360
TI  - Conformational changes of L-rRNA during elongation of polypeptide.
AB  - A ribosome undergoes significant conformational changes during elongation of a
      polypeptide chain, and these are correlated with structural changes of rRNAs. We
      tested 15 different oligonucleotides complementary to the selected, highly
      conserved seqences of rRNAs (L-rRNA, 5S rRNA and tRNA) important in protein
      biosynthesis. We carried out a reaction of binding Phe-tRNA to A site and a
      polymerization of polypeptide chains on the ribosomes converted either to pre- or
      to posttranslocational states. The inhibition of polymerization reaction by
      complementary oligonucleotides was high in all ribosomal states. The efficiency
      of inhibition of binding reaction was lower and more diverse than was the
      polypeptide elongation. We conclude that the selected oligonucleotides inhibit
      polypeptide synthesis with different effectivity, primarily depending on L-rRNA
      conformation within ribosome architecture.

PMID- 16455361
TI  - Acetolactate synthase mutation conferring imidazolinone-specific herbicide
      resistance in Amaranthus hybridus.
AB  - Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis
      of branched-chain amino acids in plants and is the target of several herbicides.
      ALS inhibitors have enjoyed popularity as herbicides due to numerous attributes,
      although their current adequacy in weed control programs is hampered by herbicide
      resistance. Most cases of ALS-inhibitor resistance have resulted from selection
      of an altered target site. The study herein reports on an alanine by threonine
      amino acid substitution at position 122 of ALS as the basis for imidazolinone
      specific resistance in an A. hybridus population from Illinois. In vitro
      inhibition of enzymatic activity (I(50)) required 1000-fold greater concentration
      of imazethapyr in the resistant population compared with a susceptible control.
      This mutation represents the second ALS alteration associated with herbicide
      resistance in a natural A. hybridus population.

PMID- 16455362
TI  - Steroids for post-tonsillectomy pain reduction: meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVES: To determine whether meta-analysis supports the use of
      corticosteroids to reduce post-tonsillectomy pain for pediatric patients.
      METHODS: A systematic review of currently available randomized controlled trials
      using a single-dose, intravenous corticosteroid during pediatric tonsillectomy
      was performed. Visual analog pain scale (VAS) data was extracted with reviewers
      blinded to results. Meta-analysis was performed with weighted mean difference and
      random-effects model using Revman 4.2 software. RESULTS: Eight randomized trials
      were included in analysis of post-tonsillectomy pain. A statistically significant
      reduction in pain as measured by VAS on postoperative day 1 was noted (mean VAS
      difference = -0.97; CI 95 % = -1.74,-0.19; P = 0.01). CONCLUSIONS: A single,
      intraoperative dose of dexamethasone may reduce post-tonsillectomy pain on
      postoperative day 1, by a factor of 1 on a 10-point pain scale. As the side
      effects and cost of dexamethasone dose appear negligible, consideration of
      routine use seems reasonable.

PMID- 16455363
TI  - Patient selection and efficacy of pillar implant technique for treatment of
      snoring and obstructive sleep apnea/hypopnea syndrome.
AB  - OBJECTIVE: Pillar implant (PIT) is a simple, office-based procedure with minimal
      morbidity that was introduced in 2003 to treat snoring and mild/moderate
      obstructive sleep apnea/hypopnea syndrome (OSAHS). We studied the: (1) success
      rate using subjective symptoms and objective polysomnographic improvement; (2)
      success rate based on BMI, OSAHS severity and Friedman tongue position (FTP); and
      (3) its value as an adjunctive or revision procedure. STUDY DESIGN AND SETTING:
      Retrospective review of 125 patients who underwent the PIT for snoring and OSAHS.
      Patients were grouped: Group I had PIT only (n = 29); Group II received
      adjunctive nasal procedures (n = 37), Group III received adjunctive oropharyngeal
      procedures (n = 55); and Group IV had failed previous UPPP (n = 4). RESULTS:
      Overall subjective and objective "cure" rates were 88.0% and 34.4%, respectively.
      Group IIb had the best objective cure rate of 46.7%. Neither AHI nor BMI
      correlated with outcome measures, whereas FTP did correlate. (FTP I and II had
      improved success vs FTP III and IV). Ten patients had partial extrusion of the
      PIT. These were removed and new PIT were carried out at a later date.
      CONCLUSIONS: Based on a short-term study, the Pillar implant is an effective
      treatment for snoring and OSAHS in selected patients and can be combined with
      adjunctive procedures to treat OSAHS.

PMID- 16455364
TI  - Evaluation of potential predictors of outcome of laser-assisted uvulopalatoplasty
      for snoring.
AB  - OBJECTIVE: Laser-assisted uvulopalatoplasty (LAUP) is a common treatment for
      snoring, but up to 50% of patients obtain little or no sustained benefit. We
      investigated whether pre-operative measurements from lateral cephalometry,
      acoustic rhinometry, analysis of snoring sounds, and body mass index (BMI) could
      predict which snorers benefited from LAUP. STUDY DESIGN AND SETTING: Fifty-five
      snoring patients were assessed pre- and 6 months post-LAUP. Snoring severity was
      assessed by objective sound level recorded during polysomnography, and a Snoring
      Symptoms Inventory (SSI) questionnaire. RESULTS: The outcome of surgery was
      assessed by changes in objective sound measurements and in SSI, 6 months after
      LAUP. CONCLUSIONS: Relationships between the predictive measurements and outcome
      were at best only weak and none had sufficient predictive value to be useful in
      clinical practice.

PMID- 16455365
TI  - Evaluation of type 3 portable monitoring in unattended home setting for suspected
      sleep apnea: factors that may affect its accuracy.
AB  - OBJECTIVE: This study evaluates the reliability of type 3 portable monitoring
      (PM) in a home setting. STUDY DESIGN AND SETTING: Prospective study in sleep
      laboratory. Type 3 device (Stardust II) was evaluated in comparison with standard
      polysomnography (PSG) among patients with obstructive sleep apnea. Quality of
      recorded data and agreement between PM and PSG results were evaluated. RESULTS:
      Low quality of recorded data was observed only in 5 cases. Pattern of disordered
      breathing was recognized correctly by PM. Apnea/hypopnea index (AHI) correlated
      well with a mean bias of 3.7 +/- 13.1/h. High sensitivity of PM was observed
      generally, whereas specificity was lower in mild patients. AHI, record time, and
      sleep position were found to be the main factors that would affect the accuracy
      of PM. CONCLUSION: Type 3 PM is feasible in unattended home-setting for routine
      examination. Influence of the factors above should be comprehensively considered
      especially for mild patients.

PMID- 16455366
TI  - The effects of melatonin on tinnitus and sleep.
AB  - GOAL: To determine if melatonin improves tinnitus and if this improvement is
      related to improvement in sleep. STUDY DESIGN AND SETTING: Prospective open-label
      study of 24 patients with tinnitus. The patients took 3 mg of melatonin per day
      for 4 weeks, followed by 4 weeks of observation. The Tinnitus Handicap Inventory
      (THI) and the Pittsburgh Sleep Quality Index (PSQI) were administered. RESULTS:
      The mean THI score decreased significantly between weeks 0 and 4, and between
      weeks 0 and 8. The mean PSQI significantly decreased between weeks 0 and 4 (P <
      0.0001), and between weeks 0 and 8 (P = 0.0003). The change in PSQI was
      significantly associated with the change in THI between weeks 0 and 4. The change
      in PSQI was not significantly associated with the change in THI between weeks 0
      and 8. The change in the PSQI in the first 4 weeks was associated with the
      initial PSQI. There was no association between the initial THI and the change in
      the THI in the first 4 weeks. CONCLUSION: Melatonin use is associated with
      improvement of tinnitus and sleep. There was an association between the amount of
      improvement in sleep and tinnitus. The impact of melatonin on sleep was greatest
      among patients with the worst sleep quality, but its impact on tinnitus was not
      associated with the severity of the tinnitus. SIGNIFICANCE: Melatonin may be a
      safe treatment for patients with idiopathic tinnitus, especially those with sleep
      disturbance due to tinnitus.

PMID- 16455367
TI  - Inhibition of post-meningitic cochlear injury with cerebrospinal fluid
      irrigation.
AB  - OBJECTIVE: Labyrinthitis ossificans, the pathologic ossification of the otic
      capsule associated with profound deafness and loss of vestibular function occurs
      frequently as a sequella of bacterial meningitis and subsequent purulent
      labyrinthitis. Experimentally, in Streptococcus pneumoniae meningitis, it has
      been shown that a vigorous inflammatory response to teichoic acids in the
      bacterial cell wall contributes to cochlear damage and subsequent fibrosis and
      ossification. The hypothesis of this study is that a dilution of concentration of
      inflammatory mediators through cerebrospinal fluid (CSF) irrigation will lead to
      a reduction in both inner ear pathology and permanent hearing loss. STUDY DESIGN
      AND SETTING: Auditory brainstem response testing was used to determine baseline
      hearing thresholds in 20 Mongolian gerbils (12 irrigated, 8 sham irrigated
      animals) at 32 kHz, 16 kHz, 8 kHz, and 4 kHz frequencies. Their thresholds at 14
      days and 120 days post-procedure were also obtained. Streptococcus pneumoniae
      meningitis was induced in both groups of animals by intrathecal (i.t.) injection
      of bacteria. Both groups received penicillin treatment. Forty-eight hours after
      inoculation, both groups were implanted with i.t. inflow and outflow catheters.
      The irrigated group was infused continuously with artificial CSF over 36 hr at a
      rate of 70 muL/hr and the outflow sampled. The tubing in the sham irrigated group
      was clamped (without sampling). They were sacrificed at 120 days post-procedure
      and histomorphometric analysis carried out. The concentration of interleukin
      1beta (IL-1beta) for the CSF samples from the irrigated group were compared to
      samples collected from an additional control group of 8 non-irrigated meningitic
      gerbils. IL-1beta was chosen to study because it is a potent pro-inflammatory
      cytokines in bacterial meningitis that is unaffected by the neurosurgical trauma
      of the experimental protocol. RESULTS: Twenty animals survived the meningitis (6
      irrigation, 6 sham irrigation, 8 non-irrigation meningitic controls). At Days 14
      and 120 post-infection, the irrigated animals manifested significantly less
      hearing loss with a mean loss of 28.82 dB compared to the sham irrigation group
      mean loss of 40.76 dB (P < 0.03). The degree of hearing loss in both groups was
      frequency-dependent with greater loss at higher frequencies (mean loss = 22.4 dB
      at 32 kHz, 23.0 dB at 16 kHz, 18.6 dB at 8 kHz, and 12.5 dB at 4 kHz).
      Histomorphometric analysis demonstrated a marked reduction in degeneration of the
      spiral ligament, spiral ganglion cells, and stria vascularis in experimental
      animals as compared to controls. Immunohistochemistry showed a significant
      reduction in IL-beta1 concentrations in the irrigated animals compared to the non
      irrigated, infected controls (P < 0.03). CONCLUSIONS: Irrigation of CSF resulted
      in a significant reduction in post-meningitic cochlear injury when compared to
      controls. This model for continuous cerebrospinal fluid irrigation provides a
      means to evaluate the effects of a dilution of inflammatory mediators on hearing
      loss and labyrinthitis ossificans after bacterial meningitis. SIGNIFICANCE:
      Despite advances in the prevention of meningitis and improved antibiotic
      treatment, bacterial meningitis continues to have significant associated
      morbidity. This study provides insight into some of the mechanisms responsible
      for post-meningitic hearing loss and labyrinthitis ossificans and presents a
      novel approach to reduce these complications.

PMID- 16455368
TI  - Hyaluronate gel stapedotomy.
AB  - OBJECTIVE: To evaluate hearing results and postoperative dizziness after
      stapedotomy with application of sodium hyaluronate gel (HG) to the oval window
      niche during fenestration of the footplate. STUDY DESIGN: Case-control study
      comparing 27 stapedotomies with HG and 32 stapedotomies without HG. OUTCOME
      MEASURE: Preoperative and postoperative audiometric data, postoperative dizziness
      (vertigo or dysequilibrium), and nystagmus. RESULTS: Postoperative hearing
      results were not statistically different for the 2 groups. There were no cases of
      postoperative sensorineural hearing loss greater than 10 dB. Early postoperative
      dizziness (chi(2) = 4.08, P = 0.043) and nystagmus (chi(2) = 5.05, P = 0.024)
      were reduced in the HG group. CONCLUSIONS: HG stapedotomy is safe and effective
      and results in less early postoperative dizziness and nystagmus when compared
      with the standard technique of stapedotomy. The application of HG to the oval
      window niche to prevent blood from entering or perilymph from escaping the
      vestibule during fenestration of the stapes footplate may contribute to a quicker
      recovery in outpatient otosclerosis surgery.

PMID- 16455369
TI  - Histologic changes in the anterior mallear ligament and the head of the malleus
      in otosclerosis.
AB  - OBJECTIVE: To determine ossicular and anterior mallear ligament (AML) changes in
      otosclerosis. STUDY DESIGN AND SETTING: Hyalinization of AML was graded as
      follows: none, patchy, or diffuse in 95 temporal bones (TBs) with otosclerosis:
      52 with stapedial fixation (SF); 43 without fixation (NSF); and 52 age-matched
      controls. Fixation of the head of the malleus was noted. RESULTS: Hyalinization
      with SF was 17 none, 23 patchy, and 12 diffuse; with NSF it was 16 none, 20
      patchy, and 7 diffuse; and in controls, 23 none, 24 patchy, and 5 diffuse. There
      was no significant difference in hyalinization among groups and no correlation
      between degree of hyalinization and age. The malleus head was fixed in 4 TBs with
      SF. CONCLUSION: Based on our findings, we do not believe that there is a
      relationship between hyalinization of the AML and otosclerosis; however,
      otosclerosis with SF seems to be a predisposing factor for fixation of the head
      of the malleus.

PMID- 16455370
TI  - Perioperative complications with the bone-anchored hearing aid.
AB  - OBJECTIVE: To discuss perioperative complications associated with the bone
      anchored hearing aid (BAHA) and their management. STUDY DESIGN AND SETTING: A
      retrospective review of 58 patients who underwent implantation of BAHA for
      unilateral conductive, mixed, or sensorineural hearing losses was performed at a
      tertiary referral center. RESULTS: Between September 2003 and June 2005, 58
      patients underwent implantation of a BAHA. There were 30 female and 28 male
      patients, with a mean age of 48 years (range 8-80 years). Complications occurred
      in 19% (11/58) of patients. Most adverse events were seen early in the series.
      The most common complication, partial or complete loss of the skin graft,
      occurred in 10% (6/58) of patients. These were managed successfully with local
      wound care. Five percent (3/58) of patients had skin growth over the abutment.
      Two of these cases were managed with office debridement, whereas 1 patient
      required revision under general anesthesia. There was implant extrusion in 3%
      (2/58) of patients, and both of these patients later underwent successful
      reimplantation. All patients had their implant activated 3 months after surgery.
      There were no perioperative or postoperative deaths. CONCLUSION: Complications
      related to BAHA implantation are relatively minor and usually involve partial or
      complete loss of the skin graft. Most complications were successfully managed in
      the office.

PMID- 16455371
TI  - Comparison of intradermal dilutional testing with the Multi-Test II applicator in
      testing for mold allergy.
AB  - OBJECTIVES: To compare and correlate wheal size using the Multi-Test II
      applicator with the endpoint obtained by intradermal dilutional testing (IDT) for
      common mold allergens. To validate the safety and efficacy of modified
      quantitative testing (MQT) for determining immunotherapy starting doses. STUDY
      DESIGN AND SETTING: Prospective study of 86 subjects with Multi-Test II and IDT
      for 6 common mold antigens. RESULTS: There was 84% concordance between IDT
      results and the results expected from the MQT method. When IDT and MQT results
      differed, the MQT algorithm predicted a safer endpoint for starting immunotherapy
      in all but 2 cases. CONCLUSION: The correlation between Multi-Test II and IDT is
      not strong enough to infer IDT endpoint from Multi-Test II results for molds. MQT
      is nearly as effective as formal IDT in determining endpoint. SIGNIFICANCE: MQT
      appears to be a safe method for determining starting doses for immunotherapy with
      fungal allergens.

PMID- 16455372
TI  - Proinflammatory effects of Staphylococcus aureus exotoxin B on nasal epithelial
      cells.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of Staphylococcus
      aureus exotoxin B (SE-B) on proinflammatory cytokine/chemokine releases in
      primary nasal epithelial cell cultures (NECC) of subjects with and without
      chronic rhinosinusitis (CRS). STUDY DESIGN AND SETTING: NECC (CRS: n = 14;
      CONTROLS: n = 11) were stimulated with SE-B. Protein concentrations of
      interleukin-(IL)-1beta, IL-6, and IL-8 levels were measured in NECC supernatants
      by ELISA before (T0) and after 24 hr stimulation with SE-B (T1). RESULTS: T0:
      supernatants of the NECC of CRS patients contained significant lower levels of IL
      8 (2.1 ng/ml) compared to CONTROLS (IL-8: 6.2 ng/ml; P < 0.01). T1: SE-B induced
      a significant increase of IL-6 in NECC (P < 0.001). IL-1beta was not detectable.
      CONCLUSIONS: This is the first study evaluating the effects of exotoxins on NECC.
      SE-B showed proinflammatory effects on NECC. SIGNIFICANCE: Our data suggest that
      resident NECC are involved in immunological responses to Staphylococcus aureus
      toxins, supplementing the so-called "superantigen hypothesis" in CRS.

PMID- 16455373
TI  - Correlation between middle turbinate and ipsilateral ethmoid histopathology in
      chronic rhinosinusitis.
AB  - OBJECTIVE: Study the concept of "rhinosinusitis" in patients with inflammatory
      paranasal sinus disease (IPSD). STUDY DESIGN AND SETTING: Prospective case
      control series in a tertiary care facility. Twenty-two consecutive patients with
      IPSD without polyposis were enrolled. A partial middle turbinectomy and
      ethmoidectomy were performed and the histopathologic findings of the surgical
      specimens from the 2 sites was studied. The general degree of inflammation,
      epithelial thickening, and inflammatory cell count were measured. RESULTS: The
      degree of middle turbinate inflammation correlated with that of the ipsilateral
      ethmoid sinus (Spearman's rho coefficient = 0.450; P < 0.05). Epithelial
      thickness was more prominent in the ethmoid sinus. The total inflammatory cell
      count was comparable. There was a statistically significant correlation among
      total inflammatory cell count, plasma cell count, and eosinophil count between
      the 2 sites. CONCLUSION: The ethmoid sinus inflammation in IPSD is accompanied by
      a commensurate ipsilateral middle turbinate inflammation. SIGNIFICANCE: The data
      support the use of the term "rhinosinusitis."

PMID- 16455374
TI  - Nasal airflow recovery after decongestion test is associated with bronchial
      hyperreactivity in patients with allergic rhinitis.
AB  - BACKGROUND: The decongestion test involves spraying an intranasal vasoconstrictor
      drug to evaluate the recovery of nasal airflow. OBJECTIVE: The aim of this study
      was to assess the relationship between pulmonary function (assessed by spirometry
      and methacholine challenge) and nasal airflow recovery after a topical
      vasoconstrictor had been administered in patients with allergic rhinitis
      (perennial, seasonal, or mixed allergic rhinitis). METHODS: A total of 150
      subjects were studied. The total symptom score, sensitization, and pulmonary
      function were all assessed. All subjects underwent rhinomanometry and the
      decongestion test. RESULTS: Univariate analysis revealed that nasal symptoms and
      spirometric parameters (except FEF(25-75) in subjects with seasonal allergic
      rhinitis) were not. Only bronchial hyperreactivity, assessed by methacholine
      challenge, proved to be significantly (and independently) associated with outcome
      (OR 1.45, P = 0.025). CONCLUSIONS: This study provides the first evidence of an
      association between a positive response to the decongestion test and bronchial
      hyperreactivity, assessed by methacholine challenge, in patients with allergic
      rhinitis.

PMID- 16455375
TI  - Combined endoscopic medial and external lateral orbital decompression for
      progressive thyroid eye disease.
AB  - OBJECTIVE: To compare the efficacy of endoscopic medial and lateral orbital wall
      surgery to 3-wall decompression in patients with thyroid eye disease. STUDY
      DESIGN AND SETTING: A retrospective study of patients with thyroid eye disease
      with severe proptosis, exposure keratitis, or compressive optic neuropathy was
      conducted. RESULTS: Mean reduction in proptosis was 4.37 mm in the 2-wall
      approach and 4.59 mm in the 3-wall group. Seventy-five percent of patients in the
      2-wall group demonstrated improved visual acuity; 50% improved after 3-wall
      decompression. Vertical palpebral fissure height decreased by an average of 2.50
      mm in the 2-wall group and by 2.03 mm in the 3-wall group. New onset diplopia was
      11.8% and 12.5%, respectively. CONCLUSIONS: Improvement in the degree of
      proptosis, visual acuity, and palpebral fissure height was seen in the majority
      of our patients and compared favorably to our results with 3-wall orbital
      decompression.

PMID- 16455376
TI  - Diffuse mucosal inflammation in nasal polyps and adjacent middle turbinate.
AB  - BACKGROUND: Nasal polyp (NP) is the most common mass lesion in the nose with
      unclear etiology and pathogenesis. OBJECTIVE: To investigate the association of
      allergy and type of cellular inflammation in Asian patients with NPs. METHODS:
      Immunohistochemical staining with a panel of antibodies for CD4+ and CD8+ T
      cells, B cells, Langerhans' cells, eosinophils, neutrophils, and mast cells were
      performed in pairs of NP tissue and middle turbinate (MT) biopsies from the same
      side of 48 patients and MT of controls. Serum total IgE and specific IgE to a
      panel of common local allergens were tested by the UniCAP (Pharmacia & Upjohn AB,
      Uppsala, Sweden) system. RESULTS: Atopy was found in 29.7% of NP patients. Strong
      correlations of cell scores were evidenced between the paired samples from nasal
      polyp patients. The cell patterns in nasal polyp mainly showed a combined cell
      infiltration with significantly higher CD8+ T cell, eosinophil and neutrophil
      scores, and an inverse median ratio of CD4+/CD8+ T cells as compared with the MT
      from controls. CONCLUSION: The similar immunohistochemical pattern of mucosal
      inflammation in NPs and the paired MT mucosa suggests a diffuse mucosal
      involvement. This indicates the necessity of anti-inflammatory treatment of
      changes in the adjacent nasal mucosa in addition to the surgical removal of NPs.
      Besides the well-recognized eosinophilic inflammation in Caucasian studies,
      predominant infiltration of T cells, especially CD8+ T cells, could be a key
      component underlying the pathogeneses of NPs.

PMID- 16455377
TI  - Packing in endoscopic sinus surgery: is it really required?
AB  - OBJECTIVE: The aim of this study was to evaluate the routine use of packing or
      local hemostatic agents in endoscopic sinus surgery (ESS). METHODS: Packing
      and/or hemostatic agents were used only when necessary in 100 consecutive adult
      ESS patients in a tertiary academic hospital. Necessity for packing the nose
      after excessive bleeding was analyzed in relation to demographic characteristics,
      medical history, previous surgeries, current surgical procedure, type of
      anesthesia, and amount of intraoperative bleeding. RESULTS: Three patients who
      required packing because of other reasons (such as bolstering of mucosa) were
      excluded from the study. The remaining 97 patients included 61 males and 36
      females between the ages of 16 to 86 (mean 44). Forty-nine patients underwent
      only ESS, 40 ESSs associated with nasal polypectomy, and 8 underwent other
      endoscopic procedures. Fifty-four underwent the operation under general
      anesthesia and 43 under local anesthesia. Intraoperative blood loss was less than
      30 mL in 82 patients (85%), 30 to 50 mL in 11 (11%), and more than 50 mL in 4
      (4%). In 89 patients (92%), packing or a hemostatic agent was not used. No
      patient had bleeding complications postoperatively. A comparison between patients
      who required packing to those who did not showed that the only statistically
      significant associations related to general anesthesia (P = 0.0082) and to the
      amount of intraoperative bleeding (P < 0.001). CONCLUSIONS: Most ESS procedures
      can be managed without packing or any other hemostatic measures. Local
      anesthesia, use of local vasoconstrictors, and careful operative technique
      minimize the need for nose packing, thus reducing patient's discomfort,
      postoperative complications, and cost of surgery.

PMID- 16455378
TI  - Distribution of class I and II human leukocyte antigens in the larynx.
AB  - OBJECTIVE: To examine the antigenic distribution of human leukocyte antigens
      (HLA) of the human larynx. STUDY DESIGN AND SETTING: Twelve human larynges were
      examined for Class I (HLA-A, -B, -C) and Class II (HLA-DR) histocompatibility
      antigens using mouse monoclonal antibodies in an indirect immunoperoxidase assay.
      Structures of the larynx and surrounding tissues were examined and given a
      semiquantitative score based on HLA Class I and II expression. RESULTS: The
      mucosal surface epithelium of the larynx stains 2+ or stronger for HLA Class I
      antigens and 1+ for Class II antigens. The deeper submucosal glands stain 1+ for
      Class I antigens and 2+ or stronger for Class II antigens. Thyroid cartilage
      showed 2+ or stronger staining of the chondrocytes for Class I antigens only.
      Thyroid follicular cells also stain only for Class I antigens. Perichondrium and
      Schwann cells of nerves stain stronger for Class I antigens than Class II
      antigens. Cartilage matrix, muscle cells, and axons of nerves do not stain for
      either class of antigens. Endothelium stains 3+ for both classes of antigens.
      CONCLUSIONS: The detailed distribution of major transplantation antigens in the
      human larynx is elucidated. Class II antigens implicated as initiators of organ
      transplant rejection were primarily found in 6 areas: mucosal surface epithelium,
      submucosal glands, ducts, vascular endothelium, perichondrium, and Schwann cells
      of nerves. The relevance of these findings to the initiation and detection of
      laryngeal allograft graft rejection is discussed.

PMID- 16455379
TI  - Endoscopic stapling diverticulotomy: an audit of difficulties, outcome, and
      patient satisfaction.
AB  - OBJECTIVE: To evaluate the procedure in terms of technical difficulties, patient
      satisfaction, symptom relief, recurrence, and further management. STUDY DESIGN:
      Retrospective study including 41 patients who underwent endoscopic stapling
      diverticulotomy. Clinical notes were reviewed, and patients were sent a patient
      satisfaction questionnaire. Statistical analysis was done using the chi(2) square
      test. SETTING: Teaching hospital. RESULTS: Larger pouches had the best results;
      81.578% were satisfied with the surgery, and 86.84% had improved swallowing.
      Complications presented in 6 patients (15%), including a perforated pouch and an
      esophageal perforation. Complications were more frequent in small pouches.
      CONCLUSIONS AND SIGNIFICANCE: Endoscopic stapling diverticulotomy offers rapid
      recovery in most patients, with early oral intake and short hospital stay. There
      is a high degree of symptoms relief, and the patient's satisfaction rate is high.
      The assessment of the pharyngeal pouch size is an important factor when deciding
      the best management for a patient with a pharyngeal pouch.

PMID- 16455380
TI  - Partial laser arytenoidectomy in the management of bilateral vocal fold
      immobility: a modification based on functional anatomical study of the
      cricoarytenoid joint.
AB  - OBJECTIVE: To establish the anatomical relationships between the arytenoid and
      cricoid cartilages and apply these findings to design an arytenoidectomy based on
      a sound anatomical basis. STUDY DESIGN: In 50 patients the length of the vocal
      process and the distance between vocal process tip and upper border of the
      cricoid cartilage were endoscopically measured. Twenty-five total laryngectomy
      specimens were sagittally and axially sectioned to verify the position of the
      arytenoids and their relation to the cricoid. The anatomical findings led to the
      design of laser partial arytenoidectomy and cordotomy (L-PAC), which was used in
      45 patients with bilateral cord paralysis in adduction. RESULTS: The anatomical
      findings showed that the cricoarytenoid joint did not contribute to the airway in
      any of the measured specimens. Using L-PAC, 100% of the patients were
      decannulated and no patient needed a postoperative tracheostomy at any time. Only
      3 patients experienced minimal postoperative aspiration to liquids (6.7%).
      Reasonable phonation was achieved as regarded by a speech analysis battery. Three
      patients (6.7%) needed a contralateral L-PAC. CONCLUSIONS: The shape of the
      cricoid and the location of its axis of maximum width ought to dictate the
      technique of glottic widening to be used in bilateral cord immobility in
      adduction. The present extra-articular technique, L-PAC, showed its versatility
      in providing an effective balance between the protective, the respiratory, and to
      lesser extent the phoniatory functions.

PMID- 16455381
TI  - Histopathologic and cytopathologic diagnostic discrepancies in head and neck
      region: pitfalls, causes, and preventive strategies.
AB  - BACKGROUND: Clinicians commonly utilize fine needle aspiration biopsy (FNAB) for
      the primary investigation of head and neck masses. Correlation of these results
      with the surgical resection diagnosis is an essential part of quality control and
      assurance programs in all cytology laboratories. METHODS: Of 610 cases, 20 (3.3%)
      had corresponding surgical resections performed within 3 months of the FNAB, with
      a discrepant diagnosis identified through a search that involved all FNABs
      performed on the head and neck region, excluding the thyroid gland, at Wayne
      State University between 1999 and 2004. Sites of discrepant samples included the
      parotid or submandibular gland (n = 5), lymph nodes (n = 8), and
      paratracheal/paraesophageal neck masses (n = 7). RESULTS: The reasons of false
      negative FNABs included sampling errors (n = 3), insufficient material for an
      adequate interpretation (n = 5), lack of triage necessary for ancillary studies
      (n = 4), and interpretation errors (n = 6). There were 2 false-positive FNABs,
      both reported as mucoepidermoid carcinoma and showed chronic sialadenitis in one
      and lymphoepithelial cyst in the other. CONCLUSIONS: FNAB is an effective tool
      for the diagnosis and triage of patients with head and neck masses that can be
      further improved with an onsite immediate adequacy evaluation and triage
      performed by a pathologist.

PMID- 16455382
TI  - Radial forearm free flap donor site outcomes comparison by closure methods.
AB  - OBJECTIVE: To compare the functional and aesthetic outcomes of radial forearm
      free flap (RFFF) donor sites reconstructed with full-thickness skin graft (FTSG),
      split thickness skin graft (STSG) alone, and STSG overlying an acellular dermal
      matrix (AlloDerm). STUDY DESIGN AND SETTING: A cross-sectional cohort study at a
      tertiary care hospital. RESULTS: Twenty-five head and neck cancer patients who
      underwent reconstruction with RFFF completed the evaluations (STSG = 10, FTSG =
      8, STSG with AlloDerm = 7). Subjective evaluations of postoperative function by
      questionnaires showed no significant differences among the 3 groups (P = 0.93).
      In blinded evaluations by surgeons, the STSG group obtained the highest aesthetic
      outcome score (3.39 of 5.0), followed by FTSG (2.89) and STSG with AlloDerm
      (2.80). However, the difference was not statistically significant (P = 0.32).
      Objective measurements of postoperative function by certified occupational
      therapists were comparable among the 3 groups with the exception of a mildly
      decreased range of wrist flexion (P = 0.036) and ulnar deviation (P = 0.016) in
      the FTSG group. CONCLUSIONS: The 3 methods of reconstruction have comparable
      postoperative functional and aesthetic outcomes. SIGNIFICANCE: Each of the 3
      methods of reconstruction has low morbidity and satisfactory aesthetic and
      functional outcomes.

PMID- 16455383
TI  - In vivo characterisation of parathyroid lesions by use of gamma probe: comparison
      with ex vivo count method and frozen section results.
AB  - OBJECTIVE: In this study we hypothesized that if timing of gamma probe-guided
      parathyroidectomy were individualized according to an optimal-time-to-surgery
      technique, in vivo characterization of parathyroid lesions would be possible. We
      compared our findings with an ex vivo counting method ("20% rule") and frozen
      section results. STUDY DESIGN AND SETTINGS: Thirty-five patients who were
      referred for surgical treatment of hyperparathyroidism were studied. Maximum
      parathyroid to thyroid sestamibi uptake ratio (UR(max)) was measured by use of
      preoperative dynamic scintigraphy. The interval between sestamibi injection and
      UR(max) was defined as the optimal time to surgery. On the day of surgery, the
      patients received the same dose of sestamibi and were taken to the operating room
      at UR(max) as determined by preoperative scintigraphy. Intraoperative in vivo
      gamma probe counts from parathyroid lesions were compared with in vivo
      contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid
      counts relative to postexcision background of the adjacent normal tissue (ex
      vivo/Bkg). RESULTS: A total of 70 excised lesions were evaluated. In vivo/Bkg
      counts obtained from parathyroid adenoma were significantly different from
      parathyroid hyperplasia (z = -3.093, P = 0.002) and other lesions (z = -3.958, P
      = 0.0001). By receiver operating characteristic curve (ROC) analysis, we found
      the cutoff value for the in vivo/Bkg counts ratio to be 103% to differentiate
      parathyroid adenoma from hyperplasia with a sensitivity, specificity, and
      accuracy of 82.5, 65, and 74.4%, respectively. On the other hand, sensitivity,
      specificity, and accuracy of the ex vivo/Bkg method to differentiate parathyroid
      adenoma from hyperplasia with a cutoff value of 34.7 was found to be 70.8%, 60%,
      and 65.9%, respectively. The difference between the accuracy of these 2 tests was
      not significant statistically (P = 0.137). Sensitivity of frozen section to
      differentiate parathyroid adenoma and hyperplasia was 76.2% and 33.3%,
      respectively. CONCLUSIONS: Patient-specific optimal protocol for timing of
      sestamibi injection together with in vivo/Bkg method is a useful alternative
      method in guiding the surgeon to differentiate parathyroid adenoma from
      parathyroid hyperplasia and other tissues and may help surgeons' decisions during
      the operation. Combined use of in vivo/Bkg and ex vivo/Bkg methods may give more
      accurate results than frozen section.

PMID- 16455384
TI  - Epithelial lacrimal gland tumors: a clinicopathological study of 18 cases.
AB  - OBJECTIVE: The aim of this study was to report the clinicopathological features
      of 18 epithelial tumors of the lacrimal gland treated in a single institution.
      STUDY DESIGN AND SETTING: Clinical data and treatment were recorded and
      histological features reviewed. RESULTS: Twelve tumors (66.7%) were adenoid
      cystic carcinoma (ACC), 5 (27.8%) pleomorphic adenoma (PA), and 1 (5.5%)
      carcinoma ex pleomorphic adenoma. All patients with ACC presented with advanced
      clinical stage, and most were treated by wide surgical resection followed by
      adjuvant radiotherapy. No recurrence was observed in 4 cases of ACC; however, 7
      patients died from persistence of disease or by local and/or distant recurrence.
      All PA patients were successfully treated by surgical resection. CONCLUSIONS:
      Epithelial lacrimal gland tumors are mainly PA and ACC, and malignancies are more
      common than benign tumors. Although ACC presented typically with advanced
      clinical stage, 33% of the patients survived without tumor recurrence or
      metastasis.

PMID- 16455385
TI  - Commentary on "Endoscopically directed middle meatal cultures versus maxillary
      sinus taps in acute bacterial maxillary rhinosinusitis: a meta-analysis".

PMID- 16455386
TI  - Lingual tonsillectomy using bipolar radiofrequency plasma excision.

PMID- 16455387
TI  - Serum leptin levels in patients with allergic rhinitis.
AB  - OBJECTIVE: To investigate the serum leptin levels in patients with allergic
      rhinitis during the symptomatic period. STUDY DESIGN AND SETTING: A randomized,
      prospective study was performed on 26 adult patients with allergic rhinitis and
      20 control subjects with similar age, sex and body mass index in a tertiary
      otolaryngology center. RESULTS: Leptin levels were 28.8 +/- 14.1 ng/mL in the
      patients with allergic rhinitis, and 20.8 +/- 13.5 ng/mL in the control group
      respectively. The difference between the groups was statistically significant (p
      = 0.04). CONCLUSION: Serum leptin levels were found to be significantly higher in
      patients with allergic rhinitis in symptomatic period. SIGNIFICANCE: Apart from
      its primary role in the regulation of body weight and energy expenditure, leptin
      may have a role in the inflammatory process of the allergic rhinitis.

PMID- 16455388
TI  - Cerebrospinal fluid leak in the neck: a rare complication of glomus vagale
      excision.

PMID- 16455389
TI  - A thyroarytenoid muscle tear presenting as a vocal cord granuloma.

PMID- 16455390
TI  - Pseudoaneurysm of the internal carotid artery after retropharyngeal abscess.

PMID- 16455391
TI  - A rare etiology of bilateral vocal fold paresis: multinodular goiter.

PMID- 16455392
TI  - Inverted papilloma with new bone formation in ethmoidofrontal region.

PMID- 16455393
TI  - Spindle cell carcinoma of the larynx with actinomyces chondritis of the larynx
      and trachea.

PMID- 16455395
TI  - Bioethics of appearance and the quality of life issue: who makes the decision?

PMID- 16455394
TI  - Supraglottic myxedema presenting as acute upper airway obstruction.

PMID- 16455397
TI  - Conductive hearing loss in facial nerve schwannoma.

PMID- 16455399
TI  - Effects of static and radiofrequency magnetic field inhomogeneity in ultra-high
      field magnetic resonance imaging.
AB  - To characterize the severe static (B(0)) and radiofrequency (B(1)) magnetic field
      inhomogeneity in ultra-high field (> or =7 T) magnetic resonance imaging,
      gradient echo (GE) and spin echo (SE) images of in vivo and postmortem human
      brains were acquired. The B(0) and B(1) inhomogeneity were experimentally mapped
      and/or numerically simulated, and correlated with the image artifacts. Whereas
      B(0) inhomogeneity affects predominantly GE images near air/tissue interfaces,
      B(1) inhomogeneity affects SE images more severely and shows non-intuitive
      patterns. Mapping of the B(0) and B(1) inhomogeneity is important in
      characterizing image artifacts. This will help develop better B(0) and B(1)
      inhomogeneity correction methods.

PMID- 16455400
TI  - Dual-acquisition phase-sensitive fat-water separation using balanced steady-state
      free precession.
AB  - Balanced steady-state free precession (SSFP) sequences use fully re-focussed
      gradient waveforms to achieve a high signal and useful image contrast in short
      scan times. Despite these strengths, the clinical feasibility of balanced SSFP is
      still limited both by bright fat signal and by the signal voids that result from
      off-resonance effects such as field or susceptibility variations. A new method,
      dual-acquisition phase-sensitive SSFP, combines the signals from two standard
      balanced SSFP acquisitions to separate fat and water while simultaneously
      reducing the signal voids. The acquisitions are added in quadrature and then
      phase corrected using a simple algorithm before fat and water can be identified
      simply by the sign of the signal. This method is especially useful for
      applications at high field, where the RF power deposition, spatial resolution
      requirements and gradient strength limit the minimum repetition times. Finally,
      dual-acquisition phase-sensitive SSFP can be combined with other magnetization
      preparation schemes to produce specific image contrast in addition to separating
      fat and water signals.

PMID- 16455401
TI  - Application of perceptual difference model on regularization techniques of
      parallel MR imaging.
AB  - Parallel magnetic resonance imaging through sensitivity encoding using multiple
      receiver coils has emerged as an effective tool to reduce imaging time or to
      improve image SNR. The quality of reconstructed images is limited by the
      inaccurate estimation of the sensitivity map, noise in the acquired k-space data
      and the ill-conditioned nature of the coefficient matrix. Tikhonov regularization
      is a popular method to reduce or eliminate the ill-conditioned nature of the
      problem. In this approach, selection of the regularization map and the
      regularization parameter is very important. Perceptual difference model (PDM) is
      a quantitative image quality evaluation tool that has been successfully applied
      to varieties of MR applications. High correlation between the human rating and
      PDM score shows that PDM should be suitable to evaluate image quality in parallel
      MR imaging. By applying PDM, we compared four methods of selecting the
      regularization map and four methods of selecting the regularization parameter. We
      found that a regularization map obtained using generalized series (GS) together
      with a spatially adaptive regularization parameter gave the best reconstructions.
      PDM was also used as an objective function for optimizing two important
      parameters in the spatially adaptive method. We conclude that PDM enables one to
      do comprehensive experiments and that it is an effective tool for designing and
      optimizing reconstruction methods in parallel MR imaging.

PMID- 16455402
TI  - Resolution enhancement in MRI.
AB  - We consider the problem of super-resolution reconstruction (SRR) in MRI. Subpixel
      shifted MR images were taken in several fields of view (FOVs) to reconstruct a
      high-resolution image. A novel algorithm is presented. The algorithm can be
      applied locally and guarantees perfect reconstruction in the absence of noise.
      Results that demonstrate resolution improvement are given for phantom studies
      (mathematical model) as well as for MRI studies of a phantom carried out with a
      GE clinical scanner. The method raises questions that are discussed in the last
      section of the paper. Open questions should be answered in order to apply this
      method for clinical purposes.

PMID- 16455403
TI  - The role of voxel aspect ratio in determining apparent vascular phase behavior in
      susceptibility weighted imaging.
AB  - Susceptibility weighted imaging (SWI) uses apparent phase contrast to enhance the
      contrast-to-noise ratio (CNR) in the magnitude image. In theory, the apparent
      phase will depend on the aspect ratio when both venous blood and parenchyma
      occupy the same voxel. To demonstrate the maximal expected effect of the external
      field from a vein, we model the vein as an infinitely long cylinder perpendicular
      to the main magnetic field. The results show that the apparent phase of a voxel
      in the image is a function of resolution, vessel size and, to a lesser degree,
      vessel center within the voxel. The simulations explain why a negative-phase mask
      has worked in SWI processing of high-resolution images collected in the
      transverse direction, despite the expected positive-phase behavior for vessels
      perpendicular to the main field. The predicted phase behavior from the
      simulations is in good agreement with that observed from human brain datasets.

PMID- 16455404
TI  - High b-value q-space diffusion MRI in myelin-deficient rat spinal cords.
AB  - In this study, we explore the effect of the lack of myelin on the diffusion
      characteristics and diffusion anisotropy obtained from high b-value q-space
      diffusion-weighted MRI (q-space DWI) in excised rat spinal cords. Twenty-one-day
      old myelin-deficient (md) mutant (N=6) and control rats (N=6) were used in this
      study. The MRI protocol included multi-slice T(1), T(2), proton density (PD) MR
      images and high b-value q-space diffusion MRI measured perpendicular and parallel
      to the fibers of the spine. q-Space displacement and probability maps, in both
      directions, as well as displacement anisotropy maps, were computed from the
      diffusion data. At the end of the MRI protocol, representative spinal cords from
      both groups were subjected to electron microscopy (EM). The md spinal cords show
      different gray/white matter contrast in the T(1), T(2) and PD MR images as
      compared with controls. In addition, the mean displacement extracted from the
      high b-value q-space diffusion data was found to be dramatically higher in the
      white matter (WM) of the md spinal cords than the controls when diffusion was
      measured perpendicular and parallel to the fibers of the spine. However,
      interestingly, at the diffusion time used in the present study, the difference in
      the WM displacement anisotropies of the two groups was not found to be
      statistically significant. Myelin was found to have a pronounced effect on the
      diffusion characteristics of water in WM but less so on the diffusion anisotropy
      observed at the diffusion time used in the present study.

PMID- 16455405
TI  - Texture analysis of magnetic resonance images of rat muscles during atrophy and
      regeneration.
AB  - OBJECTIVES: The goals of the current study were (i) to introduce texture analysis
      on magnetic resonance imaging (MRI-TA) as a noninvasive method of muscle
      investigation that can discriminate three muscle conditions in rats; these are
      normal, atrophy and regeneration; and (ii) to show consistency between MRI-TA
      results and histological results of muscle type 2 fibers' cross-sectional area.
      METHOD: Twenty-three adult female Wistar rats were randomized into (i) control
      (C), (ii) immobilized (I) and (iii) recovering (R) groups. For the last two
      groups, the right hind limb calf muscles were immobilized against the abdomen for
      14 days; then, the hind limb was remobilized only for the R group for 40 days. At
      the end of each experimental period, MRI was performed using 7-T magnet Bruker
      Avance DRX 300 (Bruker, Wissembourg); T1-weighted MRI acquisition parameters were
      applied to show predominantly muscle fibers. Rats were sacrificed, and the
      gastrocnemius muscle (GM) was excised immediately after imaging. (A) Histology:
      GM type 2 fibers (fast twitch) were selectively stained using the adenosine
      triphosphatase (ATPase) technique. The mean cross-sectional areas were compared
      between the three groups. (B) Image analysis: regions of interest (ROIs) were
      selected on GM MR images where statistical methods of texture analysis were
      applied followed by linear discriminant analysis (LDA) and classification.
      RESULTS: Histological analysis showed that the fibers' mean cross-sectional areas
      on GM transversal sections represented a significant statistical difference
      between I and C rats (ANOVA, P<.001) as well as between R and I rats (ANOVA,
      P<.01), but not between C and R rats. Similarly, MRI-TA on GM transversal images
      detected different texture for each group with the highest discrimination values
      (Fisher F coefficient) between the C and I groups, as well as between I and R
      groups. The lowest discrimination values were found between C and R groups. LDA
      showed three texture classes schematically separated. CONCLUSION: Quantitative
      results of MRI-TA were statistically consistent with histology. MRI-TA can be
      considered as a potentially interesting, reproducible and nondestructive method
      for muscle examination during atrophy and regeneration.

PMID- 16455406
TI  - Amyotrophic lateral sclerosis with predominant pyramidal signs -- early diagnosis
      by magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) in the early
      diagnosis of amyotrophic lateral sclerosis (ALS) with predominant upper motor
      neuron (UMN) signs in the initial stage of the disease. PATIENTS AND METHOD: Two
      patients with ALS were found to have spastic quadriparesis with no wasting or
      fasciculation in the limbs in the early stage of the disease. Both were subjected
      to MRI of the head and cervical spine to look for any specific diagnostic
      feature. Both of them were followed with clinical evaluation and
      electroneuromyography (ENMG) for the definitive diagnosis of ALS. RESULTS:
      Magnetic resonance imaging showed selective degeneration of the pyramidal tracts
      in the contiguous axial cuts from subcortical white matter to cerebral peduncles.
      The finding was more visible in the coronal section. In addition, there was T1
      hyperintensity visible along the anterior aspect of the spinal cord in the
      cervical region. These findings were suggestive of ALS, the diagnosis that was
      subsequently confirmed by serial clinical follow-up and ENMG. CONCLUSION: It is
      difficult to diagnose ALS in the early stage of the disease especially if the
      pyramidal signs predominate over the lower motor neuron (LMN) signs; MRI might be
      useful in such cases.

PMID- 16455407
TI  - Investigating directed influences between activated brain areas in a motor
      response task using fMRI.
AB  - Localization of cognitive processes is a strength of functional neuroimaging.
      However, information about functional interactions between brain areas is crucial
      for a deeper understanding of brain function. We applied vector autoregressive
      modeling in the context of Granger causality as a method to analyze directed
      connectivity in a standard event-related fMRI study using a simple auditory-motor
      paradigm. The basic idea is to use temporal information in stochastic time series
      of a brain region in order to predict signal time courses in other brain regions.
      Thus, we predicted that the method should demonstrate causal influence of the
      auditory cortex and the supplementary motor area (SMA) on primary motor cortex.
      Eleven right-handed healthy female subjects were instructed to press a ball with
      either their left or their right hand when hearing the command "left" or "right"
      in the scanner. Influence to the left motor cortex was found from bilateral
      auditory cortex as well as from the SMA in 9 of 11 subjects. Granger causality to
      the right motor cortex existed from bilateral auditory cortex in 5 and from SMA
      in 6 subjects. Granger causality to the SMA existed from right auditory cortex in
      7 subjects and from left auditory cortex in 8 subjects. Our findings in a simple
      task show that even under suboptimal circumstances (a relatively long TR of 2440
      ms), Granger causality can be a useful tool to explore effective connectivity.
      Temporally optimized scanning should increase that potential.

PMID- 16455408
TI  - Intraindividual variability of striatal (1)H-MRS brain metabolite measurements at
      3 T.
AB  - PURPOSE: To measure possible positional and diurnal physiological effects on
      brain metabolites in single-voxel proton magnetic resonance spectroscopy ((1)H
      MRS) measurements of the right and left striatum. METHODS: (1)H-MRS measurements
      were performed in 10 healthy adult volunteers using a short echo PRESS sequence
      (TE=30 ms, TR=3000 ms). Each individual was scanned during both morning and
      afternoon hours. Regions of interest were right and left striatum. To control for
      systematic drift in scanner performance, (1)H-MRS measurements of a standard
      phantom solution were also acquired. Statistical analysis was performed using a
      repeated measures analysis of variance that included three within-subject
      factors: metabolite (N-acetyl-aspartate [NAA] or creatine [Cr]), laterality (left
      or right caudate) and time (morning or afternoon). RESULTS: A significant
      interaction (P<.016) between time of day and metabolite levels was observed.
      Further exploration of this finding revealed a significant difference between
      morning and afternoon levels of NAA (P<.044) but not Cr. In addition, no
      significant morning-to-afternoon differences were observed for the (1)H-MRS
      phantom measurements. CONCLUSIONS: Systematic variation due to scanner
      performance does not account for the changes observed in repeated measurements of
      striatal NAA levels. This difference may be accounted for by either repositioning
      effects or circadian physiological effects. Further studies are required to learn
      whether time of day standardization of (1)H-MRS acquisitions may contribute to
      improved reproducibility of measurements.

PMID- 16455410
TI  - Three-dimensional magnetic resonance imaging after ultrasonography for assessment
      of fetal gastroschisis.
AB  - A 24-year-old woman (Gravida I, Para I) at estimated 32 weeks of pregnancy was
      referred to our department for evaluation of a suspected fetal gastroschisis.
      Ultrasound scan revealed multiple loops of dilated bowel outside the fetal
      abdomen and absence of membrane surrounding the herniated loops of the
      intestines. Three-dimensional (3D) magnetic resonance imaging was performed to
      obtain more information on the bowel both outside and inside the abdomen. Images
      were constructed with T1-weighted fat-suppressed 3D fast low-angle shot sequences
      using a maximum intensity projection algorithm. The 3D images made possible the
      realization of fetal bowel conditions with greater definition and accuracy.

PMID- 16455409
TI  - Blackberry (Rubus spp.): a pH-dependent oral contrast medium for gastrointestinal
      tract images by magnetic resonance imaging.
AB  - In this study, seven fruits have been tested on their magnetic properties,
      paramagnetic metal content and contrast enhancement in magnetic resonance imaging
      (MRI) of phantom and in vivo. Magnetic susceptibility was determined for the
      fruit pulps, as well as the contents of paramagnetic metals; iron, manganese and
      copper. The total content of these metals was 4.3, 8.6, 11.1, 10.9, 12.3, 8.3 and
      29.3 mg/kg of fruit for plum, blueberry, apple (red), pineapple, beet, grape,
      blackberry, respectively, and with magnetic susceptibility of -2.29+/-0.07, 
      2.43+/-0.07, -2.13+/-0.07, -1.84+/-0.02, -1.75+/-0.01, -1.78+/-0.06, -2.18+/-0.07
      SI, respectively. T(1)- and T(2)-weighted MR images were performed for the seven
      fruits and water (chi= -9.98 x 10(-3) SI) and in one subject. While there was no
      correlation between the magnetic susceptibility and contrast enhancement, there
      is a correlation with the total paramagnetic metal content determined with
      contrast enhancement in MRI. Thus, blackberry (Rubus spp.) contrast enhancement
      was the highest among the fruits in T(1)-weighted images. Furthermore, this
      fruit's contrast enhancement shows to be pH-dependent. These characteristics and
      the wide availability of the Rubus spp. suggest that it should be implemented as
      an oral contrast agent in images by MR to assess the function of the gastric
      section of the GI tract. Furthermore, it has the advantage of being a natural
      meal, so that it can be well tolerated by the patients and use as much as it is
      needed without side effects.

PMID- 16455411
TI  - Magnetic resonance spectroscopy: a noninvasive diagnosis of gliomatosis cerebri.
AB  - Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of neoplastic
      glial cells with preservation of neuronal architecture. It can be very difficult
      to diagnose during life because the clinical manifestations are protean and tests
      are often nondiagnostic. The diagnosis of GC needs to be based on radiological,
      clinical and pathological criteria. We present a patient with GC, which initially
      presented as acute stroke attack. We discuss the usefulness of noninvasive
      methods, such a MR spectroscopy, in the diagnosis, grading and management of GC.

PMID- 16455413
TI  - Echocardiography in women.

PMID- 16455415
TI  - Real-time 3-dimensional echocardiographic imaging of congenital heart disease
      using matrix-array technology: freehand real-time scanning adds instant
      morphologic details not well delineated by conventional 2-dimensional imaging.
AB  - OBJECTIVE: We sought to investigate whether real-time (RT) 3-dimensional
      echocardiography (RT3D) using matrix-array technology could resolve a specific
      morphologic detail that could not be well resolved during conventional 2
      dimensional (2D)/Doppler echocardiographic imaging of congenital heart disease.
      BACKGROUND: Although 2D echocardiography is currently the primary imaging
      modality of congenital heart disease, there are still some anatomic details that
      cannot be well delineated by that modality. METHODS: In all, 70 patients
      underwent RT3D examination using matrix-array transducer. Applying the standard
      sweeping technique as for 2D imaging, freehand RT imaging was used for immediate
      feedback. The 2D examinations of the last 23 consecutive patients were used to
      validate the additional value of RT3D by 3 examiners blinded to the findings of
      RT3D. RESULTS: The adequacy of 2D imaging to resolve the morphologic detail in
      question ranged from 30% to 70%, whereas RT3D imaging was considered successful
      in delineating the morphologic detail in 80% to 100% of patients instantly. The
      image resolution was superior or equivalent to that obtained by 2D imaging. Heart
      valves, septal defects, and volumetric valvular and vascular color flow
      morphologies were well delineated by RT3D. CONCLUSION: Matrix-array RT3D is a
      significant breakthrough technology that allowed instant visualization of cardiac
      anatomic details that could not be well delineated by 2D imaging. Further
      improvements of some technical limitations should make RT3D matrix-array cardiac
      imaging a significant modality in the field of echocardiographic imaging of
      congenital cardiac anomalies.

PMID- 16455416
TI  - Real-time 3-dimensional echocardiography for prosthetic valve endocarditis:
      initial experience.
AB  - Real-time 3-dimensional echocardiography is a relatively new technology with
      rapidly growing potential applications. Prosthetic valve endocarditis is still a
      challenging diagnosis despite improvements in image qualities obtained by both
      transthoracic and transesophageal echocardiograms. The purpose of this article is
      to present 4 cases of suggested prosthetic valve endocarditis, in which real-time
      3-dimensional echocardiography was performed, and to discuss the potential use of
      real-time 3-dimensional echocardiography for this application.

PMID- 16455417
TI  - Dynamic quantitative echocardiographic evaluation of mitral regurgitation in the
      operating department.
AB  - Hemodynamic modifications induced by general anesthesia could lead to
      underestimation of mitral regurgitation (MR) severity in the operating department
      and potentially serious consequences. The intraoperative severity of MR was
      prospectively compared with the preoperative baseline evaluation using dynamic
      quantitative transesophageal echocardiography in 25 patients who were stable with
      MR 2/4 or greater undergoing coronary bypass, mitral valve operation, or both.
      Significant changes in the severity of MR using transesophageal echocardiographic
      criteria occurred after the induction of general anesthesia and with
      phenylephrine. Quantitative transesophageal echocardiographic evaluation of MR
      using effective orifice area and vena contracta, and the use of phenylephrine
      challenge, were useful to avoid underestimating MR severity in the operating
      department.

PMID- 16455418
TI  - Intracardiac echocardiography for percutaneous mitral valve repair in a swine
      model.
AB  - BACKGROUND: High-quality live imaging assessment of cardiac valves and cardiac
      anatomy is crucial for the success of percutaneous catheter-based mitral valve
      (MV) repair techniques. We examined the use of intracardiac echocardiography
      (ICE) in providing online ICE images necessary for successful perctunaneous MV
      repair by Alfieri stitch technique-based percutaneous edge-to-edge device in a
      swine model. METHODS: ICE was performed in 20 healthy adult pigs (90 +/- 8 kg,
      mean +/- SEM). A 10F ICE catheter was advanced through the left femoral vein and
      the right jugular vein. Images were obtained from the right atrium, left atrium,
      right ventricle, and pulmonary artery. Fluoroscopy was used to locate the
      position of ICE catheter tip in different imaging windows. RESULTS: An
      echocardiographic protocol was developed for focused visualization of target
      cardiac structures during the process of percutaneous MV repair. This included
      visualization of interatrial septum to guide transeptal puncture; to confirm
      transit of guidewire into the left atrium, across the MV into the left ventricle
      and across the aortic valve into the aorta; to assist in central positioning of
      guide catheter in the left atrium above and then across MV leaflets; and to
      visualize middle scallops of anterior and posterior MV leaflets in short- and
      long-axis views. Finally, location and orientation of the orifice of the therapy
      catheter against each MV leaflet was visualized to enable successful capture of
      MV leaflets, to confirm successful deployment of suture and double orifice
      (figure of 8" appearance of MV, and finally to confirm central deployment of clip
      at the site of suture. CONCLUSION: An ICE protocol was developed to visualize
      serial cardiac structures to guide deployment of suture into the A2-P2 scallops
      of the MV and to confirm final result before release of clip.

PMID- 16455419
TI  - Effects of ultrasound contrast agents on Doppler tissue velocity estimation.
AB  - The combination of Doppler tissue imaging and myocardial contrast
      echocardiography has the potential to provide information about motion and
      perfusion of the myocardium in a single examination. The purpose of this study
      was to establish how the presence of ultrasound contrast agent (UCA) affects
      measurements of Doppler tissue velocities in vivo and in vitro. We performed
      echocardiography in 12 patients with ischemic heart disease before and
      immediately after a slow intravenous infusion of the UCA Optison, using color
      Doppler tissue imaging to examine the effect of contrast agents in vivo. The
      myocardial peak systolic velocities and their integrals were analyzed in
      digitally stored cineloops before and after contrast administration. To
      distinguish between methodologic and physiologic factors affecting the
      measurement of tissue velocity in vitro, experiments with a rotating disk and a
      flow cone phantom were also carried out for the 3 contrast agents: Optison,
      Sonovue, and Sonazoid. In vivo results show that the values for peak systolic
      velocity increased by about 10% during contrast infusion, from mean 5.2 +/- 1.8
      to 5.7 +/- 2.3 cm/s (P = .02, 95% confidence interval 2%-16%). The increase in
      myocardial peak systolic velocities was verified in experimental models in which
      the UCA increased the estimated mean velocity in the order of 5% to 20% for the
      motion interval of 5 to 7 cm/s, corresponding to the myocardial velocities
      studied in vivo. The response was similar for all 3 contrast agents and was not
      affected by moderate variations in concentration of the agent. We have shown that
      the presence UCA will affect Doppler tissue measurements in vivo and in vitro.
      The observed bias is presumed to be an effect of harmonic signal contribution
      from rupturing contrast agent microbubbles and does not indicate biologic or
      physiologic effects.

PMID- 16455420
TI  - Noninvasive diagnosis of restenosis by transthoracic Doppler echocardiography
      after percutaneous coronary intervention: comparison with exercise Tl-SPECT.
AB  - OBJECTIVE: Noninvasive methods that have the ability to accurately detect
      restenosis have been desired in the selection of patients requiring further
      angiographic evaluation. The present study sought to evaluate the diagnostic
      potential of transthoracic Doppler echocardiography (TTDE), a noninvasive method
      for evaluating coronary flow velocity reserve (CFVR), in detecting restenosis
      after percutaneous coronary intervention (PCI). METHODS: We studied 107
      consecutive patients 6 months after undergoing successful PCI on the left
      anterior descending coronary artery (LAD) lesions for relief of angina pectoris.
      The flow velocity in the distal LAD was measured by TTDE both at rest and during
      intravenous infusion of adenosine triphosphate. CFVR was calculated as the ratio
      of hyperemic to basal mean diastolic flow velocities. We defined a reversible
      perfusion defect in exercise Tl-201 single-photon emission computed tomography
      (SPECT) as restenosis. The CFVR measurements by TTDE were compared with the
      results of SPECT. RESULTS: Complete TTDE data were acquired for 105 of the 107
      study patients. A contrast agent was used to obtain adequate Doppler signals in
      29 patients. Of the 105 patients, there were 18 patients with abnormal perfusion
      (group A) and 87 patients with normal perfusion (group B) in the LAD territories
      on Tl-201 SPECT. CFVR was greater in group B than in group A (1.7 +/- 0.5 vs. 3.7
      +/- 0.8, P < 0.0001, respectively). There were 17 patients with CFVR < 2 and 88
      patients with CFVR > or = 2. CFVR < 2 predicted restenosis determined by Tl-201
      SPECT, with a sensitivity of 94% and a specificity of 100%. CONCLUSIONS:
      Noninvasive measurement of CFVR by TTDE accurately reflects the physiological
      severity of coronary narrowing due to restenosis after PCI. This method has
      possibility of reducing the number of unnecessary coronary angiographies after
      PCI.

PMID- 16455421
TI  - Effects of levosimendan on left ventricular diastolic function after primary
      angioplasty for acute anterior myocardial infarction: a Doppler echocardiographic
      study.
AB  - BACKGROUND: Levosimendan is a new Ca-sensitizing drug with combined positive
      inotropic and vasodilatory effects that offers new therapeutic possibilities in
      patients with severe heart failure. Compared with other inotropic agents, animal
      studies demonstrated that levosimendan does not impair left ventricular diastolic
      function. OBJECTIVE: We sought to evaluate the effects of levosimendan on left
      ventricular diastolic function, using conventional transmitral Doppler and
      Doppler tissue imaging parameters, in patients with anterior acute myocardial
      infarction undergoing primary angioplasty. METHODS: After a successful primary
      angioplasty, we randomized 52 consecutive patients with anterior acute myocardial
      infarction to levosimendan or placebo infusion and analyzed the diastolic
      function using conventional transmitral Doppler flow and Doppler tissue imaging
      at mitral annulus. RESULTS: At 24 hours after the index intervention, patients
      treated with levosimendan (n = 26) showed a significant reduction of the
      isovolumetric relaxation time (114.6 +/- 15.1-69.2 +/- 5.6 milliseconds; P =
      .001) and the ratio between the early diastolic flow and early tissue velocity
      (E/E') (21.4 +/- 10.7-12.8 +/- 7.3; P = .04), and a significant increase of the
      ratio between the early and late diastolic flow (E/A) (0.86 +/- 0.33-1.52 +/-
      0.88; P = .03) and E' (6.4-7.9 cm/s; P = .001). On the other hand, only a
      significant increase in E/A ratio (0.97 +/- 0.32-1.64 +/- 0.51; P = .002) was
      observed in the placebo group (n = 26). CONCLUSIONS: Levosimendan, after primary
      angioplasty in patients with anterior acute myocardial infarction, appears to
      improve the Doppler echocardiographic parameters of left ventricular diastolic
      function.

PMID- 16455422
TI  - Usefulness of ventricular longitudinal contractility assessed by Doppler tissue
      imaging in the prediction of reverse remodeling in patients with severe left
      ventricular systolic dysfunction.
AB  - OBJECTIVE: We sought to test if assessment of ventricular longitudinal
      contractility (LC) by Doppler tissue imaging (DTI) can predict reverse remodeling
      (RR) of left ventricular (LV) dysfunction resulting from medical treatment.
      METHODS: DTI was performed in 35 patients with nonischemic LV dysfunction
      (ejection fraction 26 +/- 7%) and LC was assessed at the 4 different basal
      segments of the LV walls (septal, lateral, inferior, and anterior) using
      myocardial velocity curves and strain measurements; the peak systolic or delayed
      longitudinal contraction velocity of LV walls only with concomitant negative
      strain were measured and added to represent LC of each patient (LC by DTI).
      Successful RR was defined as a reduction of LV end-systolic volume of greater
      than 15%. RESULTS: RR was observed in 13 patients (37%, group A). Initial LV
      ejection fraction was similar in patients who did and did not achieve RR (group
      B). Compared with group B, group A showed shorter QRS interval (110 +/- 36 vs 136
      +/- 28 milliseconds, P = .022), shorter symptom duration (2.3 +/- 3.5 vs 4.2 +/-
      3.4 years, P = .047), lower prevalence of left bundle branch block (23% vs 59%, P
      = .039), and higher value of LC by DTI (9.6 +/- 3.5 vs 6.3 +/- 3.6 cm/s, P =
      .011). Multivariate analysis revealed that symptom duration less than 2 years
      (odds ratio = 8.0, 95% confidence interval = 1.3-47.2, P = .022) and LC by DTI
      (odds ratio = 1.3, 95% confidence interval = 1.0-1.7, P = .019) were independent
      predictors of RR. CONCLUSIONS: DTI provides a new index of LC, which is useful
      for predicting RR in patients with severe LV dysfunction.

PMID- 16455423
TI  - Optimization of pulsed wave tissue Doppler to predict left ventricular reverse
      remodeling after cardiac resynchronization therapy.
AB  - OBJECTIVE: The optimal use of pulsed wave Doppler tissue imaging (DTI) in
      predicting left ventricular (LV) reverse remodeling after cardiac
      resynchronization therapy (CRT) was investigated. METHODS: DTI was performed in
      69 patients before and 3 months after CRT. Echocardiographic reverse remodeling
      was observed in 38 patients. LV dyssynchrony was measured with the time to onset
      or peak systolic velocity in 2- and 6-basal segment models. RESULTS: The time to
      onset and either the standard deviation of 6 segments of > 20 ms or a delay of >
      or = 60 ms between any 2 of 6 segments had a similar predictive accuracy
      (sensitivity, 97% and 95%, respectively; specificity, 74% and 73%, respectively).
      The time to peak systolic velocity or evaluating 2 segments was less accurate.
      CONCLUSIONS: Evaluation of 6 segments is necessary to predict LV reverse
      remodeling after CRT. The time to onset of systolic velocity is superior to the
      time to peak velocity.

PMID- 16455424
TI  - What is the optimal clinical technique for measurement of left ventricular volume
      after myocardial infarction? A comparative study of 3-dimensional
      echocardiography, single photon emission computed tomography, and cardiac
      magnetic resonance imaging.
AB  - BACKGROUND: Left ventricular (LV) volumes have important prognostic implications,
      but are commonly underestimated. We sought accuracy and reproducibility of LV
      volume measurement by live 3-dimensional (3D) echocardiography (3DE) and TI-201
      single photon emission computed tomography (SPECT), compared with cardiac
      magnetic resonance imaging (MRI). METHODS: In all, 30 patients (age 62 +/- 9
      years, 23 men) underwent LV volume assessment with 3DE, SPECT, and cardiac MRI
      after myocardial infarction. LV volumes were measured using a semiautomated
      border detection algorithm for 3DE, gated SPECT software for SPECT, and a 3D
      display for MRI. Results of 3DE and SPECT volumes were compared with MRI as the
      standard of reference. RESULTS: The 3DE volumes showed excellent correlation with
      cardiac MRI (end-diastolic volume [EDV], r = 0.90, P = .001; end-systolic volume
      [ESV], r = 0.94, P = .001), as did SPECT (EDV, r = 0.89, P = .001; ESV, r = 0.95,
      P = .001). However, both 3DE and SPECT underestimated LV volumes. The mean MRI
      EDV was 179 +/- 56 mL compared with 3DE (mean difference, -10 +/- 26 mL, P = .04)
      and SPECT (mean difference, -58 +/- 28 mL, P < .001). There was a significant
      difference between SPECT EDV and 3DE (mean difference, -48 +/- 31 mL, P < .001).
      The mean MRI ESV was 96 +/- 54 mL and this was underestimated by SPECT (mean
      difference, -22 +/- 19 mL, P < .001), but not by 3DE (mean difference, -0.9 +/-
      19 mL, P = not significant). ESV was also underestimated when SPECT was compared
      with 3DE (mean difference, -22 +/- 27 mL, P < .001). The results of 3DE were
      reproducible with excellent intraobserver (ESV, r = 0.98, -2 +/- 6 mL; EDV, r =
      0.98, -1 +/- 6 mL, P = .001) and interobserver (ESV, r = 0.97, -2 +/- 6 mL; EDV,
      r = 0.95, -3 +/- 10 mL, P = .001) correlation. CONCLUSION: We have shown that 3DE
      is accurate and reproducible for the measurement of LV volumes for risk
      assessment in chronic ischemic heart disease and dilated cardiomyopathy.
      Furthermore, 3DE is more accurate than TI-201 SPECT with less underestimation of
      LV volumes.

PMID- 16455425
TI  - Preservation of ventricular function in amateur athletes after completion of a
      marathon.
AB  - BACKGROUND: Previous studies have demonstrated the development of impaired
      systolic function and new segmental wall motion abnormalities following
      completion of ultraendurance events. Limited information is available on the
      effect of an endurance event such as a marathon on the left ventricular indices
      and hemodynamics. METHODS: We examined 45 patients (26 men, 19 women with the
      average age of 35+/- 8 years) who successfully trained and completed the 2001
      Chicago Marathon (26.2 miles). Transthoracic 2-dimensional and Doppler
      echocardiography (TTE) was preformed prior to the marathon (17+/-10.7 days),
      immediately following the marathon (71+/-42 minutes), and at follow-up (29+/-12.9
      days). RESULTS: Left ventricular end diastolic volumes declined immediately post
      marathon and returned to baseline at the one-month follow-up. Ejection fraction
      was maintained and no regional wall motion abnormalities were identified at any
      time point. Diastolic parameters decreased immediately post marathon but returned
      to baseline during follow-up principally reflecting a change in volume status.
      CONCLUSION: Marathon running by a group of well-trained recreational athletes
      does not result in impairment of left ventricular systolic or diastolic function.

PMID- 16455426
TI  - The Tei index identifies a differential effect on left and right ventricular
      function with low-dose anthracycline chemotherapy.
AB  - OBJECTIVE: We sought to study the relative effect on left ventricular (LV) and
      right ventricular (RV) function of low-dose anthracycline-containing chemotherapy
      regimes. METHODS: A total of 23 patients (mean age 48 +/- 20 years) underwent
      echocardiographic examinations before any anthracycline had been administered and
      then after low-dose anthracycline (doxorubicin 50-125 mg/m2). The Tei index was
      used to compare the relative effects on RV and LV function. RESULTS:
      Anthracycline administration was significantly associated with an increase in the
      LV Tei index (0.38 +/- 0.12 vs 0.46 +/- 0.16, P = .02). There was no significant
      change in the RV Tei index (0.19 +/- 0.10 vs 0.20 +/- 0.10, P = .72). Comparing
      the relative effect on global LV and RV function the change in LV Tei was
      significantly greater than the change in RV Tei (0.07 +/- 0.13 vs 0.01 +/- 0.09,
      P = .044). CONCLUSIONS: Low-dose anthracycline administration has a significant
      negative impact on LV function but does not affect RV function.

PMID- 16455427
TI  - Left atrial appendage function in patients with systemic embolism in spite of in
      sinus rhythm.
AB  - OBJECTIVE: We sought to investigate whether left atrial (LA) appendage (LAA)
      function was impaired in patients with systemic embolism in sinus rhythm.
      METHODS: Transesophageal echocardiography was performed in 7 patients within 5
      days after embolism (early group) and in 32 patients, more than 5 days after
      embolism (late group). We searched intracardiac thrombus and determined LAA area
      and LAA flow velocity, and the grade of spontaneous echocontrast. RESULTS: LA
      thrombus could be detected in 2 of the 39 patients only in early group (P =
      .028). The patients of early group, as compared with late group, had lower LAA
      flow velocity (28 +/- 16 vs 60 +/- 26 cm/s, P = .007) and higher grade of
      spontaneous echocontrast score (1.14 +/- 1.46 vs 0.25 +/- 0.62, P = .013). LA
      dimension and LAA area were not statistically different. CONCLUSION: LAA function
      may be impaired early after embolism even in sinus rhythm.

PMID- 16455428
TI  - A critical review of patent foramen ovale detection using saline contrast
      echocardiography: when bubbles lie.
AB  - Saline and indocyanine green dye were the first agents noted to produce a
      contrast effect when injected peripherally during M-mode echocardiographic
      imaging, although it was subsequently found that almost any type of injected
      solution would have this effect. These first-generation contrast agents were
      limited to opacification of right heart structures, and they prompted subsequent
      development of agents that traverse pulmonary circulation. Although opacification
      limited to right heart structures is considered a limitation of these first
      generation agents, this is an advantage when attempting to identify the presence
      of right-to-left shunt. First-generation air contrast is considered the gold
      standard for identification of patent foramen ovale (PFO). However, PFO
      investigators have used varying criteria to define abnormal contrast studies.
      There are also multiple mechanisms by which saline contrast studies may produce
      both false-positive and false-negative results for presence of PFO. There is
      mounting experimental evidence that PFO is associated with cerebral ischemia and
      migraine headache, with a resulting evolution of devices for percutaneous closure
      of these shunts. Echocardiographic physicians must be aware of potential pitfalls
      of the air contrast technique to avoid exposing patients to unnecessary risk of
      closure devices, and missing the potential benefit of shunt closure in
      appropriately selected patients.

PMID- 16455429
TI  - Validation of a carotid intima-media thickness border detection program for use
      in an office setting.
AB  - BACKGROUND: A unique semiautomated border detection program (BDP) designed for
      use on a personal computer was evaluated to determine whether: (1) carotid intima
      media thickness (CIMT) measurements were bioequivalent to a reference laboratory;
      and (2) it would allow a novice (NOV) reader with no medical training to
      accurately and reproducibly measure CIMT. METHODS: Far-wall CIMT was measured
      blindly and in duplicate by an experienced and NOV reader using BDP and by a
      reference laboratory. RESULTS: Mean CIMT using BDP was bioequivalent to the
      reference laboratory (two 1-sided T-test, P < .05) with small absolute
      differences (experienced 0.011 +/- 0.004 mm, NOV 0.022 +/- 0.004 mm).
      Reproducibility was high, with small coefficients of variation when used by
      either the experienced (3.1%) or NOV (7.8%) reader. CONCLUSION: CIMT measurements
      using BDP were accurate and reproducible. It was mastered easily by a NOV reader
      and appeared suitable for use in an office setting.

PMID- 16455430
TI  - Intracoronary stent visualized on transesophageal echocardiogram in a case of
      coronary dissection complicated by aortic dissection.
AB  - We present a case of a patient presenting with a myocardial infarction with
      subsequent coronary intervention resulting in a coronary dissection complicated
      by an aortic dissection. The coronary dissection was treated with coronary
      stents. Transesophageal echocardiogram visualized the intracoronary stent within
      the intimal flap of the aortic dissection. The aortic dissection was successfully
      managed conservatively.

PMID- 16455431
TI  - Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia:
      an echocardiographic perspective.

PMID- 16455432
TI  - The echocardiographic evaluation of intracardiac masses: a review.
AB  - Echocardiography is an invaluable procedure for the evaluation of intracardiac
      masses, and can reliably identify mass location, attachment, shape, size, and
      mobility, while defining the presence and extent of any consequent hemodynamic
      derangement. With careful attention to mass location and morphology, and
      appropriate application of clinical information, echocardiography can usually
      distinguish between the 3 principal intracardiac masses: tumor, thrombus, and
      vegetation. Transesophageal imaging frequently adds additional important
      information to the assessment of mass lesions and should always be considered
      when image quality is inadequate or pertinent clinical questions remain
      unanswered with surface imaging. This review will focus on primary and metastatic
      tumors of the heart.

PMID- 16455433
TI  - Angle correction for proximal isovelocity surface area method: is it spheric cap
      or lune?

PMID- 16455434
TI  - Challenges: the continued gap between research and professional practice.

PMID- 16455436
TI  - Health services use and growth patterns among older siblings of infants with
      prenatal drug exposure.
AB  - The health care use patterns, suspected maltreatment, and growth trajectories of
      siblings of infants with prenatal drug exposure were examined. Ninety-three
      siblings of drug-exposed infants were matched with patients from the same primary
      care clinic. The case patients were found to have significantly fewer health care
      contacts, more deficient immunizations, and more reports of suspected child
      maltreatment. Although they did not differ in birth weight, growth curve modeling
      found that case patients had lower weight gain trajectories. When drug-exposed
      infants are identified, nursing personnel are in a unique position to assist the
      siblings of those identified infants obtain needed medical care and services.

PMID- 16455435
TI  - Research on psychoneuroimmunology: tai chi as a stress management approach for
      individuals with HIV disease.
AB  - Psychoneuroimmunology is a framework for mind-body practice and research that
      combines cutting-edge scientific exploration with holistic philosophy to
      appreciate and understand stress responses. The rapidly growing research
      literature provides a foundation for building an integrative stress management
      model with the potential to positively influence the stress-disease relationship
      and, ultimately, health outcomes. This article introduces a novel tai chi
      intervention and provides quantitative and qualitative data from a randomized
      clinical trial indicating its effects on psychosocial variables in individuals
      living with various stages of HIV disease.

PMID- 16455437
TI  - Adding story-centered care to standard lifestyle intervention for people with
      Stage 1 hypertension.
AB  - This study examined the blood pressure (BP)-lowering effect of adding story
      centered care (i.e., carefully attending to another's narrative) to standard
      lifestyle intervention (i.e., exercise training and nutrition counseling) for
      people with Stage 1 hypertension. The subjects (N = 24), who were university and
      hospital employees, were unmedicated and received standard lifestyle
      intervention; half were randomly assigned to story-centered care. Their 24-hour
      BP was measured four times at 8-week intervals, twice before and twice after the
      intervention. Subjects who received story-centered care had greater decreases (p
      < .05) in awake systolic BP over the 6-month study period. Neither systolic nor
      diastolic sleep BP was significantly affected. Story-centered care showed promise
      for contributing to the BP-lowering effect of lifestyle intervention. Approaches
      for integrating story-centered care into the treatment of people with
      hypertension are challenging but warrant further attention.

PMID- 16455438
TI  - The effectiveness of hand acupuncture and moxibustion in decreasing pain and
      "coldness" in Korea women who have had hysterectomy: a pilot study.
AB  - This pilot study compared the relative effectiveness of hand acupuncture and
      moxibustion in relieving pain and decreasing "coldness" in certain body parts
      experienced by subjects who have undergone a hysterectomy. The study participants
      were 10 women between 40 and 65 years, whose hysterectomies had been performed
      within 5 years before the study. The 10 subjects were divided randomly into two
      independent experimental groups, with one group being treated with hand
      moxibustion, whereas the other group received hand acupuncture therapy. The
      visual analogue scale evaluation tool was used to measure the pain and digital
      infrared thermographic imaging to measure "coldness" and blood circulation. When
      measuring the degree of pain, it was noted that pain scores decreased
      conspicuously over time. The responses of the two groups did not differ
      significantly, but moxibustion therapy was found to increase the temperature of
      internal parts of the body (i.e., abdominal and waist areas), whereas acupuncture
      affected the peripheral parts of the body.

PMID- 16455439
TI  - Patterns of recovery following percutaneous coronary intervention: a pilot study.
AB  - Percutaneous coronary intervention (PCI) is the most common type of cardiac
      revascularization performed. However, there has been limited research examining
      the recovery of PCI patients after their hospital discharge. This descriptive,
      longitudinal study examined patterns of recovery (cardiac symptoms experienced,
      impact of cardiac symptoms on physical functioning and enjoyment of life,
      postprocedure problems experienced, and functioning) of 37 PCI patients at 2, 4,
      and 6 weeks following PCI. Fatigue was the most frequent and persistent symptom,
      and significantly, F(2, 26) = 3.6, p < .05, it impacted physical functioning at 4
      weeks following PCI. Both physical and psychosocial functioning improved over
      time. Coronary restenosis and heart rhythm disturbance were the most common self
      reported heart-related problems. Understanding normal variation in recovery
      patterns can assist clinicians in developing interventions to facilitate optimal
      outcomes.

PMID- 16455440
TI  - Is verbatim transcription of interview data always necessary?
AB  - Verbatim transcription of interview data has become a common data management
      strategy in nursing research and is widely considered to be integral to the
      analysis and interpretation of verbal data. As the benefits of verbal data are
      becoming more widely embraced in health care research, interviews are being
      increasingly used to collect information for a wide range of purposes. In
      addition to purely qualitative investigations, there has been a significant
      increase in the conduct of mixed-method inquiries. This article examines the
      issues surrounding the conduct of interviews in mixed-method research, with
      particular emphasis on the transcription and data analysis phases of data
      management. It also debates on the necessity to transcribe all audiorecorded
      interview data verbatim, particularly in relation to mixed-method investigations.
      Finally, it provides an alternative method to verbatim transcription of managing
      audiorecorded interview data.

PMID- 16455441
TI  - Describing the health parameters of outpatients with schizophrenia.
AB  - Few studies have examined the physical health parameters of persons with
      schizophrenia. This pilot study describes the physical health and psychiatric
      symptoms in outpatients with schizophrenia. Participants (N = 11) were recruited
      from a population of persons with schizophrenia receiving care at an outpatient
      clinic in a Veterans Affairs hospital located in the southeast. Following the
      granting of medical clearance, data regarding sociodemographics and prescribed
      medications were collected via record review. Physical health parameters included
      6-minute walking distance, body mass index, and percentage of body fat.
      Functional health status was measured using the Duke Health Profile. Psychiatric
      symptoms were measured using the Positive and Negative Syndrome Scale. A trained
      research assistant performed all measures in private offices at the study site.
      Most participants met the criteria for being classified as overweight or obese
      and demonstrated poor aerobic fitness. More research is needed to examine
      responses of veterans with schizophrenia to interventions designed to improve
      physical health parameters.

PMID- 16455442
TI  - Internet research in an international context.
AB  - Computers and the Internet provide researchers with new options in surveying.
      When using electronic surveys, several practical and methodological issues need
      to be considered such as whether the majority of the surveyed population has
      Internet access and whether an e-mail or a Web-based survey is most appropriate.
      Other important considerations relate to Internet security issues and, in
      international research, the possibility of language barriers. Despite these
      challenges, electronic surveys offer a promising alternative to conventional mail
      surveys.

PMID- 16455443
TI  - Multilevel models in health outcomes research. Part I: Theory, design, and
      measurement.

PMID- 16455444
TI  - Feasibility of bioelectrical impedance analysis in children with a severe
      generalized cerebral palsy.
AB  - OBJECTIVE: The need is strong for an accurate and easy-to-perform test to
      evaluate the nutritional state of children who have a severe generalized cerebral
      palsy, defined as a severe motor handicap and an intellectual disability. For
      that purpose, we determined the feasibility of bioelectrical impedance analysis
      (BIA) in these children and evaluated their nutritional state. METHODS: BIA
      recordings were done in 35 children who had a severe generalized cerebral palsy
      using a single-frequency BIA device. In addition, arm span and body weight were
      determined. Components of feasibility were whether the children tolerated the
      recording and felt comfortable and whether the recording could be performed in a
      reproducible way (prescribed body position and stable resistance and reactance
      values). All recordings were performed at specialized children's daycare centers
      or schools. RESULTS: One child (3%) did not tolerate the recording, whereas the
      remaining 34 children (71%) felt comfortable. Most children (74%) could be placed
      in the prescribed position, but stability of resistance values was low. Stability
      of resistance values was positively influenced by older age, a quiet location for
      the recording, feeling comfortable, and a small number of people in the room. For
      29 children, we were able to calculate values for total body water and fat-free
      mass. Compared with age-matched reference values, these values were significantly
      decreased in all age groups. CONCLUSIONS: The present pilot study has
      demonstrated that BIA recording is a feasible nutritional assessment method in
      children who have severe generalized cerebral palsy. Because the test procedure
      was well tolerated by most children, its value for use in this specific
      population deserves further investigation.

PMID- 16455445
TI  - Effect of homocysteine on platelet activation induced by collagen.
AB  - OBJECTIVE: The present study investigated the effects of homocysteine on platelet
      activation induced by collagen and the downstream signaling pathways potentially
      involved in these effects. METHODS: Washed human platelets were incubated with
      homocysteine and collagen type I. The effects of homocysteine on platelet
      aggregation and adhesion and the tyrosine phosphorylation of total platelet
      proteins, Src kinase, and phospholipase-Cgamma2 (PLCgamma2) were studied.
      RESULTS: Homocysteine (10 to 100 microM) increased collagen-induced aggregation
      of washed platelets. Upon homocysteine (50 to 100 microM) treatment, platelet
      deposition to collagen-coated surface was significantly augmented under the low
      shear rate model (100/s) but not under the high shear rate model (1600/s).
      Collagen-stimulated total protein tyrosine phosphorylation in platelets was
      further enhanced by incubation with homocysteine. This effect was almost
      abrogated by genistein. Homocysteine potentiated collagen-stimulated tyrosine
      phosphorylation of the Src kinase and PLCgamma2, which was partly decreased by
      integrin beta1 blocking antibody. CONCLUSION: Homocysteine (at 10 to 100 microM)
      potentiates collagen type I induced-platelet activation through signaling
      components of glycoprotein VI and integrin alpha2beta1 pathway. Our results
      suggested that upregulation of tyrosine phosphorylation of proteins such as Src
      and PLCgamma2 is involved in the downstream signaling events of homocysteine
      stimulation in human platelets.

PMID- 16455446
TI  - Nutritional status and food intake in nine patients with chronic low-limb ulcers
      and pressure ulcers: importance of oral supplements.
AB  - OBJECTIVES: Chronic low-limb ulcers and pressure ulcers are a serious and costly
      issue. Malnutrition is a risk factor. Searching for intervention strategies in
      elderly patients referred for surgical closure of their ulcers, the trial aimed
      at investigating the micronutrient status, determining the food intake of such
      patients, and the role of oral liquid supplements. METHODS: Observational cohort
      study in 9 patients, starting 5 days prior to surgery until day 10 after surgery.
      VARIABLES: body mass index (BMI), food intake assessed using standardized meals
      (energy target 25 kcal/kg/day). Oral liquid supplements were provided between
      meals. Laboratory: blood count, plasma proteins, antioxidant status, vitamins,
      Fe, Se, and Zn. RESULTS: The patients were aged 71+/-10 y (mean+/-SD), with a BMI
      of 23.3+/-3.3. Baseline blood samples showed anemia and strong inflammation in 4
      patients: albumin, retinol, and selenium were low; iron and zinc were very low.
      Food intake was largely variable and covered only about 76% (31-95%) of energy
      requirements. Breakfast provided 225+/-110, lunch 570+/-215, and dinner 405+/-150
      kcal. Supplements were willingly consumed covering 35+/-12% of energy target.
      While vitamin supply was adequate, selenium and zinc requirements were not met.
      CONCLUSIONS: Most patients with chronic skin ulcers suffered micronutrient status
      alterations, and borderline malnutrition. Meals did not cover energy
      requirements, while oral supplements covered basic micronutrient requirements and
      compensated for insufficient oral energy and protein intakes, justifying their
      use in hospitalized elderly patients.

PMID- 16455447
TI  - Does the intraoperative peritoneal lavage cytology add prognostic information in
      patients with potentially curative gastric resection?
AB  - Peritoneal recurrence is the foremost pattern of failure after potentially
      curative resection for gastric cancer. Our aim was to evaluate the prognostic
      value of intraperitoneal free cancer cells (IFCCs) in peritoneal lavage of
      patients who underwent potentially curative resection for gastric carcinoma. Two
      hundred twenty patients with gastric cancer stage I, II, or III were
      prospectively evaluated with peritoneal lavage and cytologic examination.
      Aspirated fluid from the abdominal cavity was centrifuged and subjected to
      Papanicolaou staining. The mean age was 60.9 years (range, 21-89 years), and
      63.6% were men. IFCCs were detected in 6.8% of the patients; suspicious in 2.7%,
      and negative in 84.5%. No judgment could be given in 5.9% of the cases. Invasion
      of the gastric serosa (pT3) was observed in all positive cytology patients.
      Patients with IFCCs had a mean survival time of 10.5 months, while those with
      negative IFCC had a mean survival time of 61 months (P = 0.00001). There was no
      correlation between the presence of IFCCs and tumor size, histology, pN, or tumor
      site. Our conclusions are that (1) positive cytology indicates a poor prognosis
      in patients who underwent potentially curative gastric resection and (2)
      peritoneal lavage cytology improves staging in assessing these patients and may
      alter their therapeutic approach.

PMID- 16455448
TI  - The split-stomach fundoplication after esophagogastrectomy.
AB  - Two complications associated with esophagogastrectomy are anastomotic leak and
      gastroesophageal reflux. We describe here a modification of an intrathoracic
      esophagogastrostomy using the gastric fundus to address these issues. After
      completion of the esophagogastrectomy, the fundus is divided to produce "wings."
      After the esophagogastrostomy is performed, the wings are used to form a wrap
      around the anastomosis. This wrap is secured to the esophagus and to the stomach.
      All patients undergoing the split-stomach fundoplication were compared with all
      patients undergoing standard esophagogastrectomies. End points were in-hospital
      mortality, anastomotic leak, and postoperative endoscopic dilation. All living
      patients were contacted and questioned about refluxlike symptoms and completed
      the Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL)
      symptom severity questionnaire. Twenty-six patients underwent the split-stomach
      fundoplication (wrap group), compared to 54 patients undergoing standard
      resection (no wrap group). Occurrence of end points in the wrap vs. no wrap
      groups were, respectively, in-hospital mortality, 3.8% vs. 7.4% (P = NS);
      anastomotic leak, 0% vs. 17% (P = 0.03); reflux symptoms 20% vs. 60% (P < 0.001);
      postoperative dilation, 40% vs. 30% (P = NS). The median total GERD-HRQL score
      was 5 for the wrap group vs. 14 for the no wrap group (P = 0.03). The addition of
      the split-stomach fundoplication to esophagogastrectomy may decrease the
      incidence of anastomotic leak and postoperative refluxlike symptoms.

PMID- 16455449
TI  - Gallbladder cancer: an analysis of a series of 139 patients with invasion
      restricted to the subserosal layer.
AB  - The goal was to study our experience in the management of a series of patients
      with a potentially curative subserosal gallbladder cancer who were prospectively
      treated by the authors. Between April 1988 and July 2004, 139 patients were
      enrolled in our prospective database. Of the above, 120 were operated on with an
      open procedure and the rest with laparoscopic surgery. In only eight patients was
      the diagnosis suspected before the cholecystectomy. The majority of tumors were
      adenocarcinoma. Six patients had an epidermoid tumor, and one had a
      carcinosarcoma. Of the patients, 74 underwent reoperation, while in 55 (70.2%) it
      was possible to perform an extended cholecystectomy with a curative aim.
      Operative mortality was 0%, and operative morbidity was 16%. Lymph node
      metastases were found in 10 (18.8%), while in 7 (13.2%) the liver was involved.
      The overall survival rate was 67.7%, while in those who underwent resection, the
      survival rate was 77%. Through the use of a multivariate analysis, the presence
      of lymph node metastasis was found to be an independent factor with respect to
      prognosis. The feasibility of performing an extended cholecystectomy in patients
      with gallbladder cancer and invasion of the subserosal layer allows for a good
      survival rate. The presence of lymph node metastases represents the main poor
      prognosis factor, and some type of adjuvant therapy should be studied in this
      particular group.

PMID- 16455450
TI  - Nonalcoholic Fatty gallbladder disease: the influence of diet in lean and obese
      mice.
AB  - The obesity epidemic has contributed to an increased prevalence of gallstones and
      a higher percentage of chronic acalculous cholecystitis. Obesity is associated
      with Type II diabetes and hyperlipidemia in murine models. In addition, we have
      previously demonstrated that serum glucose, insulin, cholesterol, and
      triglycerides correlated with gallbladder contractility in murine models.
      However, the relative role of insulin resistance and gallbladder fat infiltration
      in this phenomenon remain unclear. Therefore, we tested the hypothesis that
      gallbladder wall lipids are related to obesity and diet and are inversely
      correlated with gallbladder contractility. One hundred lean control (C7BL/6J) and
      36 obese leptin-deficient (Lep(ob)) 8-week-old female mice were fed either a chow
      diet or a 1.0% cholesterol, 15% butterfat (high-lipid) diet for four weeks.
      Pooled gallbladders were then analyzed for free fatty acids (FFA), phospholipids
      (PL), total cholesterol (TC), and triglycerides (TG). Cholesterol/phospholipid
      ratios were then calculated. The Lep(ob) mice fed a chow diet had significantly
      higher (P < 0.01) gallbladder lipids than the three other groups. The lean mice
      that were fed a high-lipid diet had increased (P < 0.05) gallbladder TC compared
      to the lean mice on a chow diet. In addition, the cholesterol/phospholipid ratio
      was significantly increased (P < 0.01) in the lean mice fed a high-lipid diet
      compared to the other three groups. Finally, the high-lipid diet decreased
      gallbladder FFA (P < 0.01), PL (P = 0.08), and TC (P < 0.05) in Lep(ob) mice.
      These data suggest that (1) obese mice have increased gallbladder lipids; (2) a
      high-cholesterol, high-fat diet increases gallbladder lipids and the
      cholesterol/phospholipid ratio in lean mice; but (3) decreases gallbladder fatty
      acids, phospholipids, and cholesterol in obese mice. Prior studies have
      documented similarly decreased gallbladder response to neurotransmitters in obese
      mice on a chow diet, as well as lean and obese mice on a high-lipid diet.
      Therefore, we conclude that leptin-deficient obesity and/or a high-fat diet
      causes nonalcoholic fatty gallbladder disease, which is manifested by diminished
      gallbladder contractility.

PMID- 16455451
TI  - SURGISIS-assisted surgical site control in the delayed repair of a complex bile
      duct injury after laparoscopic cholecystectomy.
AB  - Although laparoscopic cholecystectomy has revolutionized the surgical approach to
      patients with gallbladder disease, it has also brought a marked increase in the
      incidence of complex and serious bile duct injuries. Many of these major injuries
      represent a major technical challenge for even the most seasoned hepatobiliary
      trained surgeon. Herein, we present a case outlining the algorithmic treatment
      approach for delayed-presentation complex biliary injury and report on the novel
      use of small intestinal submucosal biomaterial for surgical site control in the
      staged repair of a complex biliary injury (Strasberg E4) after laparoscopic
      cholecystectomy.

PMID- 16455452
TI  - A structurally optimized celecoxib derivative inhibits human pancreatic cancer
      cell growth.
AB  - Deregulation of the phosphatidylinositol 3-kinase (PI-3K)/PDK-l/Akt signaling
      cascade is associated with pancreatic cancer tumor invasion, angiogenesis, and
      tumor progression. As such, it has been postulated that PDK-1/Akt signaling
      inhibitors may hold promise as novel therapeutic agents for pancreatic cancer.
      Disadvantages of currently available Akt inhibitors include tumor resistance,
      poor specificity, potential toxicity, and poor bioavailability. Previous studies
      have demonstrated that OSU-03012, a celecoxib derivative, specifically inhibits
      PDK-1 mediated phosphorylation of Akt with IC(50) values in the low muM range.
      Human pancreatic cancer cell lines AsPC-1, BxPC-3, Mia-PaCa 2, and PANC-1 were
      cultured in media containing varying concentrations of OSU-03012, 5-fluorouracil
      (5-FU), and gemcitabine, and changes in Akt phosphorylation and cell viability
      were evaluated using western blotting and a 3-(4, 5-dimethylthiazolyl-2)-2, 5
      diphenyltetrazolium bromide (MTT) assay, respectively. Treatment with OSU-03012
      resulted in decreased PDK-1-mediated Akt phosphorylation and cell growth
      inhibition for all cell lines with IC(50) values ranging between 1.0 and 2.5 muM.
      Resistance to 5-FU and gemcitabine was observed in cell lines AsPC-1 and BxPC-3.
      Further analyses indicate that OSU-03012 induces both proapoptotic and
      antiproliferative effects in these cells. Taken together, these data suggest that
      OSU-03012 has potential value as a novel therapy for pancreatic cancer.

PMID- 16455453
TI  - Method of pyloric reconstruction and impact upon delayed gastric emptying and
      hospital stay after pylorus-preserving pancreaticoduodenectomy.
AB  - Preservation of the pylorus at the time of pancreaticoduodenectomy has been
      associated with equal oncological outcomes when compared to the classical Whipple
      operation. Multiple studies have demonstrated that pylorus-preserving
      pancreaticoduodenectomy (PPPD) has equal or superior outcomes regarding quality
      of life when compared with the traditional Whipple operation, but many studies
      have suggested a higher incidence of delayed gastric emptying (DGE). DGE prolongs
      hospital stay, and its association with PPPD has hampered its adoption by many
      pancreatic surgery centers. We describe a novel surgical technique for the
      prevention of delayed gastric emptying following pylorus-preserving
      pancreaticoduodenectomy. The technique of pyloric dilatation appears to decrease
      the incidence of delayed gastric emptying and facilitates earlier hospital
      discharge, when compared with standard pylorus preserving
      pancreaticoduodenectomy.

PMID- 16455454
TI  - Combined hepatic and inferior vena cava resection for colorectal metastases.
AB  - Surgical resection continues to offer the only hope for cure of colorectal cancer
      metastatic to the liver. Tumor involvement of the vena cava is often viewed as a
      contraindication to surgical resection. Whereas proven technically feasible, the
      survival advantages of en bloc liver and vena cava resection remain unclear. We
      reviewed all patients at a tertiary care center who had resection of colorectal
      liver metastases, including those with vena cava resections. Eleven patients had
      en bloc liver and vena cava resection between 1988 and 2002; during the same time
      period, 97 patients underwent isolated liver resection. There were no
      perioperative deaths in the 11 patients. All resections had negative histological
      margins. Mean follow-up was 33 months from the date of surgery. Median disease
      free survival of the group having caval resections was 9 months, whereas median
      survival was 34 months. When compared to the cohort of isolated hepatic
      resections, the group undergoing caval resections experienced a significantly
      reduced disease-free survival of 18.6 vs. 9.1 months, respectively (P = 0.03);
      however, there was no difference in overall survival between the two groups at
      55.2 vs. 34.3 months, respectively (P = 0.20). Colorectal liver metastases
      involving the vena cava should be considered for surgical resection.

PMID- 16455455
TI  - Management of pain in small duct chronic pancreatitis.
AB  - Small duct chronic pancreatitis (CP) is defined by a nondilated main pancreatic
      duct, and the morphological and clinical features of chronic pancreatitis with
      pain are the most prominent symptoms. Current treatment strategies are based on
      pain history and the location and extent of disease. Traditionally, radical
      pancreatic resectional procedures have been carried out for small duct CP,
      especially with an associated head mass of uncertain aetiology. Based on the
      information from five randomized trials, the duodenum-preserving pancreatic head
      resection and its modifications have proven to provide excellent long-term pain
      relief and to be superior to more radical operations. Therefore, these procedures
      can be considered the standard for small duct CP with head dominant disease. The
      longitudinal V-shaped excision of the ventral pancreas combines extensive
      drainage and a limited resection and offers good pain relief in diffuse small
      duct CP. However, long-term results and larger series are awaited for definite
      conclusions. Thoracoscopic splanchnicectomy and endosonography-guided celiac
      plexus blocks require controlled trials before their routine use. This article
      provides an overview about the current and evidence-based pain management in
      small duct CP.

PMID- 16455456
TI  - Glutamine does not protect against hepatic warm ischemia/reperfusion injury in
      rats.
AB  - The administration of glutamine before experimental ischemia/reperfusion (I/R)
      has been shown to protect intestinal, pulmonary, and myocardial tissue by
      inducing heat shock proteins (HSP). However, it is not known whether glutamine is
      protective for all organs. We therefore tested whether pretreatment with
      glutamine reduces injury following hepatic I/R in rats. Male lean Zucker rats
      were pretreated with either glutamine (0.75 g/kg intraperitoneally, n = 6) or
      saline (n = 6), 24 and 6 hours before ischemia. Seventy percent of the liver was
      exposed to 75 minutes of warm ischemia followed by 24 hours reperfusion. Liver
      enzymes, histology, neutrophil accumulation, survival, and heat shock protein
      (HSP) 70 induction were examined. Glutamine administration did not reduce liver
      injury. In both groups, 5 of 6 animals survived 24 hours of reperfusion. There
      was no difference in serum transaminase levels with AST 15113 +/- 4336 U/L
      (glutamine) vs. 17695 +/- 8531 U/L (control, P > 0.05), and ALT 7763 +/- 2524
      (glutamine) U/L vs. 5884 +/- 2063 U/L (control, P > 0.05). The degree of
      neutrophil accumulation and necrosis was not different between groups at 24 hours
      of reperfusion. Pretreatment did not result in HSP70 upregulation in any of the
      groups. Pretreatment with glutamine did not reduce hepatic ischemia/reperfusion
      injury. The lack of protection was associated with an absence of HSP70
      upregulation prior to ischemia.

PMID- 16455457
TI  - Debunking dogma: surgery for four or more colorectal liver metastases is
      justified.
AB  - Treatment of four or more colorectal liver metastases (CRLMs) is controversial
      and remains a relative contraindication to surgery at some institutions. We
      sought to assess the outcome of patients with four or more CRLMs treated with
      surgery. Patients (159) with four or more CRLMs were treated surgically at a
      single institution. The median number of treated lesions was 5 (range, 4-14). The
      majority of patients received neoadjuvant chemotherapy (89.9%). Forty-six (29.0%)
      patients underwent resection only, 12 (7.5%) underwent radiofrequency ablation
      (RFA) only, and 101 (63.5%) underwent resection plus RFA. The 5-year actuarial
      disease-free and overall survival rates were 21.5% and 50.9%, respectively.
      Patients who underwent RFA as part of their surgical procedure (hazard ratio [HR]
      = 1.81, P = 0.03) and those with a positive surgical resection margin (HR = 1.52,
      P = 0.01) were more likely to have a shorter time to recurrence. Patients who did
      not have a reduction in tumor size following neoadjuvant chemotherapy had a
      higher likelihood of death following surgical treatment (HR = 2.53, P = 0.01).
      Patients with four or more CRLMs should be considered for aggressive surgical
      treatment, including liver resection with or without RFA, in order to improve the
      chance of long-term survival. Certain clinicopathologic factors, including lack
      of response to neoadjuvant chemotherapy, were associated with a worse prognosis.

PMID- 16455458
TI  - Transarterial chemoembolization with degradable starch microspheres, irinotecan,
      and mitomycin-C in patients with liver metastases.
AB  - Degradable starch microspheres (DSMs) provide transient occlusion of small
      arteries and are thought to improve the therapeutic effect of anticancer drugs.
      Irinotecan (CPT-11) is one of the most effective anticancer agents. We herein
      report cases with liver metastases treated with transarterial chemoembolization
      with DSM, CPT-11, and mitomycin-C (DSM-CPT therapy). Five patients underwent DSM
      CPT therapy for liver metastases that originated from colorectal cancer for four
      and gastric cancer for one. They all lack indication for surgery. They were all
      male with an age range of 42-78 years (mean, 55.2 years). Three of them had
      pretreatment histories with 5-fluorouracil or related agents, and four of them
      had combined systemic or local chemotherapy at the period. Required doses for
      stasis of whole blood flow of hepatic artery of DSMs were used with CPT-11 and
      mitomycin-C. After one to six injections, four patients had a partial response
      and the disease progressed in one patient with gastric cancer origin. Two of the
      partial response patients underwent surgery after 2 months of the partial
      response period. Carcinoembryonic antigen and CA19-9 levels in partial response
      patients decreased to 16.1% and 19.3% of the level before treatment,
      respectively. DSM-CPT therapy can be a potential therapy for liver metastases.

PMID- 16455459
TI  - Effect of gastric bypass on Barrett's esophagus and intestinal metaplasia of the
      cardia in patients with morbid obesity.
AB  - Gastric bypass in patients with morbid obesity should be an excellent antireflux
      procedure, because no acid is produced at the small gastric pouch and no duodenal
      reflux is present, due to the long Roux-en-Y limb. Five hundred fifty-seven
      patients with morbid obesity submitted to resectional gastric bypass, and routine
      preoperative upper endoscopy with biopsy samples demonstrated 12 patients with
      Barrett's esophagus (2.1%) and three patients with intestinal metaplasia of the
      cardia (CIM). An endoscopic procedure was repeated twice after surgery, producing
      seven patients with short-segment Barrett's esophagus (BE) and five patients with
      long-segment BE. Body mass index (BMI) decreased significantly, from 43.2 kg/m(2)
      to 29.4 kg/m(2) 2 years after surgery. Symptoms of reflux esophagitis, which were
      present in 14 of the 15 patients, disappeared in all patients 1 year after
      surgery. Preoperative erosive esophagitis and peptic ulcer of the esophagus
      healed in all patients. There was regression from intestinal metaplasia to
      cardiac mucosa in four patients (57%) with short-segment BE, and in one patient
      (20%) with long-segment BE. Two (67%) of three cases with CIM had regression to
      cardiac mucosa. There was no progression to low- or high-grade dysplasia. Gastric
      bypass in patients with Barrett's esophagus and morbid obesity is an excellent
      antireflux operation, proved by the disappearance of symptoms and the healing of
      endoscopic esophagitis or peptic ulcer in all patients, which is followed by an
      important regression to cardiac mucosa that is length-dependent and time
      dependent.

PMID- 16455460
TI  - Diagnosis and therapy of primary hypertrophic pyloric stenosis in adults: case
      report and review of literature.
AB  - Adult idiopathic hypertrophic pyloric stenosis (AIHPS) is a misleading anatomic
      and radio-clinical entity of unknown etiology. Only about 200 cases have been
      reported in the literature. It is a benign disease resulting from hypertrophy of
      the circular fibers of the pyloric canal. Despite the recent progress in
      radiography and endoscopy, it is very hard to define hypertrophic stenosis in
      adults. Differentiation of primary from secondary pyloric stenosis is frequently
      a task of the pathologist rather than the surgeon. The main therapy is surgical,
      although endoscopic dilatation has been tried. There remains controversy over the
      best surgical approach. A case is reported of a 48-year-old male patient with
      AIHPS who was subjected to distal gastrectomy. This paper discusses the possible
      causes of the disorder, the recommended diagnostic steps, and the different
      surgical approaches.

PMID- 16455461
TI  - Effect of Roux-en-Y gastric bypass on satiety and food likes: the role of
      genetics.
AB  - Among factors influencing the outcome of bariatric surgery may be genetics and
      familial risk. The purpose of this study was to assess the etiology of obesity
      and its impact on hunger, satiety, and food likes in obese patients undergoing
      Roux-en-Y gastric bypass (RYGB). This study was based on 76 patients undergoing
      RYGB procedures performed by a single surgeon. A previously described 100-point
      obesity risk index (ORI) was used to assess familial obesity risk. Hunger and
      satiety were assessed using a standardized Visual Analog Scale "Snickers" test,
      and food preferences for regular vs. low-fat potato chips were measured
      preoperatively and postoperatively. Patients were stratified preoperatively into
      high ORI (n = 34) and low ORI (n = 42) groups. Before operation, high-ORI
      patients preferred high-fat (regular) potato chips to low-fat (baked) potato
      chips, whereas the low-ORI patients liked both food types equivalently (P <
      0.05). After operation (n = 43), both groups showed lower preferences for high
      fat potato chips (P < 0.05 for high-ORI group). As anticipated, hunger was
      dramatically suppressed after RYGB. However, there was more satiety in the high
      ORI group (P < 0.05, ANOVA). Most patients undergoing bariatric surgery had a
      strong familial or genetic component to their disease. RYGB in high-ORI patients
      was associated with a significant decline in preference of fatty food and a
      significantly prolonged drop in hunger ratings after a fast and after a standard
      282 kcal meal. The success of bariatric surgery may be influenced by the etiology
      of obesity.

PMID- 16455462
TI  - Surgical management and complex treatment of infected pancreatic necrosis: 18
      year experience at a single center.
AB  - Infected pancreatic necrosis (IPN), the most severe form of acute pancreatitis,
      is responsible for most cases of pancreatitis-related morbidity and mortality.
      Since 1986, 220 patients with IPN have been treated. The surgical treatment was
      performed on average 18.5 days (range, 8-25 days) after the onset of acute
      pancreatitis and consisted of wide-ranging necrosectomy, combined with widespread
      drainage and continuous lavage. In 108 of the 220 cases, some other surgical
      intervention (distal pancreatic resection, splenectomy, total pancreatectomy,
      cholecystectomy, colon resection, etc.) was also performed. Following surgery,
      the supportive therapy consisted of immunonutrition (glutamine and arginine
      supplementation) and modification of cytokine production with pentoxifylline and
      dexamethasone. Continuous lavage was applied for an average of 44.5 days (range,
      21-95 days), with an average of 9.5 L (range, 5-20 L) of saline per day. The
      bacteriologic findings revealed mainly enteral bacteria, but Candida infection
      was also frequently detected (21%). Forty-eight patients (22%) had to undergo
      reoperation. The overall hospital mortality was 7.7% (17 patients died). In our
      experience, IPN responds well to adequate surgical treatment, continuous,
      longstanding widespread drainage and lavage, together with supportive therapy
      consisting of immunonutrition and modification of cytokine production, combined
      with adequate antibiotic and antifungal medication.

PMID- 16455464
TI  - Outcomes of cholecystectomy after endoscopic sphincterotomy for
      choledocholithiasis.
AB  - Laparoscopic cholecystectomy (LC) for treatment of symptomatic common bile duct
      stones (CBDS) after endoscopic sphincterotomy (ES) is associated with increased
      conversion and complications compared with other indications. We examined factors
      associated with conversion and complications of LC after ES. A retrospective
      study of 32 patients undergoing ES for CBDS followed by cholecystectomy was
      undertaken. Surgical outcomes for this group were compared with a control
      population of 499 LCs for all other indications. Factors associated with open
      cholecystectomy and complications in the ES group were analyzed. Patients
      undergoing LC preceded by ES had a significantly higher complication (odds ratio
      [OR] = 7.97; 95% CI, 2.84-22.5) and conversion rate (OR = 3.45; 95% CI, 1.56
      7.66) compared with LC for all other indications. Pre-ES serum bilirubin greater
      than 5 mg/dL was predictive of conversion (positive predictive value = 63%, P <
      0.005). Patients with symptomatic CBDS that undergo LC after ES have higher
      complication and conversion rates than patients undergoing LC without ES. Pre-ES
      serum bilirubin is useful in identifying patients who may not have a successful
      laparoscopic approach at cholecystectomy.

PMID- 16455463
TI  - Palliative surgery for unresectable pancreatic and periampullary cancer: a
      reappraisal.
AB  - This study aimed to reappraise short-term and long-term results of palliative
      biliary and gastric bypass surgery in patients with unresectable pancreatic head
      carcinoma found at explorative laparotomy. We retrospectively analyzed 83
      consecutive patients whose pancreatic head carcinoma appeared unresectable at
      laparotomy (vascular involvement [57%], liver metastases [24%], distant
      metastatic lymph nodes [11%], peritoneal implants [8%]) and who underwent
      palliative surgical concomitant biliary and gastric bypass. Postoperative
      mortality and morbidity rates were 4.8% and 26.5%, respectively. Postoperative
      delayed gastric emptying occurred in 9 patients (10%). Antecolic (46%) and
      retrocolic (54%) gastrojejunostomies did not differ for the duration of
      nasogastric suction, the delay of oral intake, and the incidence of delayed
      gastric emptying. Mean hospital stay was 16 +/- 8 days. Median survival was 9
      months (range 1-44). Late cholangitis occurred in 2 patients (2.4%) treated
      medically. One recurrent jaundice required transhepatic stenting 9 months from
      surgery. Four late gastric outlet obstructions occurred (4.8%) with a mean delay
      of 8 months from surgery. These data demonstrate that, in patients with
      unresectable pancreatic head carcinoma at laparotomy, palliative concomitant
      biliary and gastric bypass in a single procedure is safe and long-term efficient.
      This strategy remains to be compared to endoscopic palliation in this setting.

PMID- 16455465
TI  - Multiple gastrointestinal stromal tumors of the ileum and neurofibromatosis type
      1.
AB  - Type 1 neurofibromatosis, also known as von Recklinghausen disease, is one of the
      most common genetic disorders. Gastrointestinal associations have been well
      described in these patients, but the true incidence of gastrointestinal tumors
      and the proportion of these becoming clinically significant are not known. The
      most common gastrointestinal tumors are stromal tumors, most of which are located
      in the stomach and jejunum. We discuss the case of a female patient with
      neurofibromatosis whose initial diagnosis was an ovarian mass. During surgery the
      diagnosis of an intestinal stromal tumor was made. Operative findings were a
      multilobulated tumor arising from the ileal wall 50 cm from the ileocecal valve.
      The tumor did not originate from the nervous myenteric plexus or muscular layer
      of the small bowel wall; it originated from within the stromal cells of the
      intestinal wall. Mitotic count showed 3 mitoses per 10 high-power fields.
      Immunohistochemical stains of the tumor showed positive staining for CD117 and
      CD34 and negative staining for S100, alpha-smooth muscle actin, and desmin. The
      intestinal myenteric plexus showed positive staining for chromegranin A and S100.
      The histologic characteristics of this patient's tumor are compatible with an
      undifferentiated stromal tumor of nonneural or nonmuscular origin.

PMID- 16455466
TI  - Abdominal drainage was unnecessary after hepatectomy using the conventional clamp
      crushing technique.
AB  - A prophylactic abdominal drainage catheter is routinely inserted by many surgeons
      in patients after hepatic resection. Between January 2002 and September 2004, 462
      consecutive patients who had undergone hepatic resection using a clamp crushing
      method by the same surgical team were retrospectively divided into the drainage
      group (n = 357) and the nondrainage group (n = 105). There was no difference in
      hospital mortality between the two groups of patients (drainage group, 0.6% vs.
      nondrainage group, 0%; P = 1.0). However, there was a greater incidence of
      surgical complications in the drainage group (31.4% vs. 8.6%, P < 0.001), and
      greater incidence of wound complications and subphrenic complications in the
      drainage group compared to the nondrainage group (24.4% vs. 4.8%, P < 0.001). In
      addition, the mean (+/- SEM) postoperative hospital stay of the drainage group
      was 13 +/- 6.5 days, which was significantly longer than that of the nondrainage
      group (9.7 +/- 3.3 days, P = 0.001). On multivariate analysis, abdominal drainage
      and intraoperative bleeding were the independent risk factors that were
      significantly associated with the incidence of drainage-related complications.
      The results suggested that routine abdominal drainage is unnecessary after
      hepatic resection when the conventional clamp crushing method is used during
      parenchyma transection.

PMID- 16455467
TI  - Neoadjuvant radiochemotherapy for patients with locally advanced rectal cancer
      leads to impairment of the anal sphincter.

PMID- 16455469
TI  - Premium care.

PMID- 16455468
TI  - Cyclooxygenase-2 expression and clinical outcome in gastrointestinal stromal
      tumors.
AB  - The significance of cyclooxygenase-2 (COX-2) expression in mesenchymal tumors has
      not been completely described. We analyzed clinicopathologic variables and COX-2
      protein expression in all mesenchymal tumors of the GI tract that were treated at
      our institution between 1990 and 2002. Paraffin-embedded specimens were
      immunohistochemically stained for KIT and COX-2 protein. KIT-positive tumors were
      diagnosed as gastrointestinal stromal tumors (GIST). Among 42 available
      specimens, 38 tumors were diagnosed as GIST and four were non-GIST mesenchymal GI
      tumors (KIT negative). The median overall survival for the GIST patients was 34
      months. Ninety-two percent of GIST expressed COX-2 protein. COX-2 protein was not
      expressed in any of the non-GIST tumors. GIST patients with negative or low COX-2
      expression developed disease recurrence and/or died of their disease in 37% of
      the cases, compared with 18% for GIST patients with high COX-2 expression
      (difference not statistically significant). The vast majority of mesenchymal
      tumors of the GI tract are GIST that express COX-2 protein. As opposed to known
      predictors of GIST behavior such as tumor size and mitotic count, levels of COX-2
      protein expression did not correlate with clinical outcome.

PMID- 16455470
TI  - Keynote comment: Chemoprevention of cancer--time to catch up with the
      cardiologists.

PMID- 16455471
TI  - Lung cancer and exposure to environmental cadmium.

PMID- 16455472
TI  - Immunochemical testing for colorectal cancer.

PMID- 16455473
TI  - Immunomodulatory effects of non-steroidal anti-inflammatory drugs in Barrett's
      oesophagus.

PMID- 16455474
TI  - Difference in incidence of colorectal cancer between men and women in Asia.

PMID- 16455475
TI  - Environmental exposure to cadmium and risk of cancer: a prospective population
      based study.
AB  - BACKGROUND: Cadmium is a ubiquitous environmental pollutant, which accumulates in
      the human body such that 24-h urinary excretion is a biomarker of lifetime
      exposure. We aimed to assess the association between environmental exposure to
      cadmium and cancer. METHODS: We recruited a random population sample (n=994) from
      an area close to three zinc smelters and a reference population from an area with
      low exposure to cadmium. At baseline (1985-89), we measured cadmium in urine
      samples obtained over 24 h and in the soil of participants' gardens, and followed
      the incidence of cancer until June 30, 2004. We used Cox regression to calculate
      hazard ratios for cancer in relation to internal (ie, urinary) and external (ie,
      soil) exposure to cadmium, while adjusting for covariables. FINDINGS: Cadmium
      concentration in soil ranged from 0.8 mg/kg to 17.0 mg/kg. At baseline, geometric
      mean urinary cadmium excretion was 12.3 nmol/day for people in the high-exposure
      area, compared with 7.7 nmol/day for those in the reference (ie, low-exposure)
      area (p<0.0001). During follow-up (median 17.2 years [range 0.6-18.8]), 50 fatal
      cancers and 20 non-fatal cancers occurred, of which 18 and one, respectively,
      were lung cancers. Overall cancer risk was significantly associated with a
      doubling of 24-h cadmium excretion (hazard ratio 1.31 [95% CI 1.03-1.65],
      p=0.026. Population-attributable risk of lung cancer was 67% (95% CI 33-101) in
      the high-exposure area, compared with that of 73% (38-108) for smoking. For lung
      cancer, adjusted hazard ratio was 1.70 (1.13-2.57, p=0.011) for a doubling of 24
      h urinary cadmium excretion, 4.17 (1.21-14.4, p=0.024) for residence in the high
      exposure area versus the low-exposure area, and 1.57 (1.11-2.24, p=0.012) for a
      doubling of cadmium concentration in soil. INTERPRETATION: Historical pollution
      from non-ferrous smelters continues to present a serious health hazard,
      necessitating targeted preventive measures.

PMID- 16455476
TI  - Immunochemical testing of individuals positive for guaiac faecal occult blood
      test in a screening programme for colorectal cancer: an observational study.
AB  - BACKGROUND: Screening for colorectal cancer by use of guaiac-based faecal occult
      blood tests (FOBT) reduces disease-specific mortality. However, due to imperfect
      specificity, about half of individuals positive for guaiac FOBT are negative for
      neoplasia on colonoscopy. We aimed to assess whether the testing of individuals
      positive for guaiac FOBT in a screening programme for colorectal cancer by use of
      a sensitive immunochemical FOBT could select more appropriately those who should
      receive colonoscopy. METHODS: We invited individuals who were guaiac FOBT
      positive in the second screening round of a pilot study in Scotland, UK, to give
      two samples, each from separate stools, for immunochemical FOBT while awaiting
      colonoscopy. Results were classed as: both samples negative (N/N), one sample
      negative and one positive (N/P), and both samples positive (P/P); data were
      assessed for sampling bias. We compared immunochemical findings with those from
      colonoscopy using odds ratios of positive samples (P/P) versus negative (N/N and
      N/P). Sensitivity, specificity, and positive and negative likelihood ratios for
      cancer, and for cancer and high-risk adenomatous polyps were also calculated.
      FINDINGS: 1486 participants were invited and 801 (54%) sets of duplicate samples
      were returned. We found no evidence of sampling bias with regard to sex, age, or
      degree of positivity on guaiac FOBT. Of 800 sets returned with consent and
      analysed, 173 (22%) were N/N, 129 (16%) were N/P, and 498 (62%) were P/P. Chi2
      test showed a highly significant positive correlation between degree of
      positivity on guaiac FOBT and on immunochemical FOBT (p<0.003). 795 individuals
      had data for colonoscopy: one (<1%) of 171 N/N participants and one (<1%) of 127
      N/P participants had colorectal cancer, compared with 38 (8%) of 497 P/P
      participants; adenomatous polyps were found in 28 (16%) N/N individuals, 24 (19%)
      N/P individuals, and 193 (39%) P/P individuals. Normal colonoscopy was less
      common in the P/P group (85 [17%]) than in the N/N (67 [39%]) and N/P (49 [39%])
      groups. The odds ratio for P/P being associated with cancer was 7.57 (95% CI 1.84
      31.4) and with high-risk adenomatous polyps was 3.11 (1.86-5.18). Sensitivity of
      a P/P result for cancer was 95.0% (81.8-99.1), and for cancer and high-risk
      adenomatous polyps was 90.1% (84.4-94.0); specificity was 39.5% (36.0-43.1) and
      47.8% (43.9-51.8), respectively. INTERPRETATION: Immunochemical FOBT for
      individuals with positive guaiac FOBT could decrease substantially the number of
      false positives in a screening programme for colorectal cancer.

PMID- 16455477
TI  - Survival from rare cancer in adults: a population-based study.
AB  - BACKGROUND: Rare cancers are a challenge to clinical practice, and treatment
      experience, even in major cancer centres to which rare cancers are usually
      referred, is often limited. We aimed to study the epidemiology of rare cancers in
      a large population of several countries. METHODS: We analysed survival by age,
      sex, subsite, and morphology in 57,144 adults with 14 selected rare cancers
      diagnosed 1983-94. Variations in survival over time and between European regions
      were also assessed for variations in quality of care. We also estimated the
      adjusted relative excess risk of death for every rare cancer. FINDINGS: Overall 5
      year relative survival was good (ie, >65%) for placental choriocarcinoma (85.4%
      [95% CI 81.4-89.5]), thyroid medullary carcinoma (72.4% [69.2-75.5]), ovarian
      germ-cell cancer (73.0% [70.0-76.0]), lung carcinoid (70.1% [67.3-72.9]), and
      cervical adenocarcinoma (65.5% [64.3-66.6]); intermediate (ie, 35-65%) for
      testicular cancer at age 65 years or older (64.0% [59.3-68.7]), sarcoma of
      extremities (60.0% [58.9-61.2]), digestive-system endocrine cancers (55.6% [54.9
      56.3]), anal squamous-cell carcinoma (53.1% [51.5-54.8]), and uterine sarcoma
      (43.5% [42.0-44.9]); low for carcinoma of adrenal-gland cortex (32.7% [28.3
      37.2]) and bladder squamous-cell carcinoma (20.4% [18.8-22.0]); and poor for
      angiosarcoma of liver (6.4% [1.8-11.0]) and mesothelioma (4.7% [4.3-5.2]).
      Survival was usually better for women than men and poor in those aged 75 years or
      older. Survival significantly improved over time for ovarian germ-cell cancer,
      sarcomas of extremities, digestive-system endocrine tumours, anal squamous-cell
      carcinoma, and angiosarcoma of liver. Survival in northern Europe was higher than
      in the other geographic groupings for most cancers. INTERPRETATION: Because
      effective treatments are available for several of the rare cancers we assessed,
      further research is needed to ascertain why survival is lower in some European
      countries than in others, particularly in older patients. Audit of best practice
      for rare cancers with treatment protocols would be useful.

PMID- 16455478
TI  - Barriers to participation in clinical trials of cancer: a meta-analysis and
      systematic review of patient-reported factors.
AB  - BACKGROUND: Enrolling participants onto clinical trials of cancer presents an
      important challenge. We aimed to identify the concerns of patients with cancer
      about, and the barriers to, participation in clinical trials. METHODS: We did a
      systematic review to assess studies of barriers to participation in experimental
      trials and randomised trials for validity and content. We estimated the frequency
      with which patients identified particular issues by pooling across studies that
      presented data for barriers to participation in clinical trials as proportions.
      FINDINGS: We analysed 12 qualitative studies (n=722) and 21 quantitative studies
      (n=5452). Two qualitative studies inquired of patients who were currently
      enrolled onto clinical trials, and ten inquired of patients who were eligible for
      enrolment onto various clinical trials. Barriers to participation in clinical
      trials were protocol-related, patient-related, or physician-related. The most
      common reasons cited as barriers included: concerns with the trial setting; a
      dislike of randomisation; general discomfort with the research process;
      complexity and stringency of the protocol; presence of a placebo or no-treatment
      group; potential side-effects; being unaware of trial opportunities; the idea
      that clinical trials are not appropriate for serious diseases; fear that trial
      involvement would have a negative effect on the relationship with their
      physician; and their physician's attitudes towards the trial. Meta-analysis
      confirmed the findings of our systematic review. INTERPRETATION: The
      identification of such barriers to the participation in clinical trials should
      help trialists to develop strategies that will keep to a maximum participation
      and cooperation in cancer trials, while informing and protecting prospective
      participants adequately.

PMID- 16455479
TI  - Alcohol and cancer.
AB  - A causal association has been established between alcohol consumption and cancers
      of the oral cavity, pharynx, larynx, oesophagus, liver, colon, rectum, and, in
      women, breast; an association is suspected for cancers of the pancreas and lung.
      Evidence suggests that the effect of alcohol is modulated by polymorphisms in
      genes encoding enzymes for ethanol metabolism (eg, alcohol dehydrogenases,
      aldehyde dehydrogenases, and cytochrome P450 2E1), folate metabolism, and DNA
      repair. The mechanisms by which alcohol consumption exerts its carcinogenic
      effect have not been defined fully, although plausible events include: a
      genotoxic effect of acetaldehyde, the main metabolite of ethanol; increased
      oestrogen concentration, which is important for breast carcinogenesis; a role as
      solvent for tobacco carcinogens; production of reactive oxygen species and
      nitrogen species; and changes in folate metabolism. Alcohol consumption is
      increasing in many countries and is an important cause of cancer worldwide.

PMID- 16455480
TI  - Use of brachytherapy in children with cancer: the search for an uncomplicated
      cure.
AB  - Brachytherapy is a sophisticated radiation method in which radioisotopes are
      placed inside or at a short distance from the tumour. The volume of tissue that
      receives the prescribed dose of radiotherapy is therefore fairly small compared
      with that used in standard radiotherapy techniques. In paediatric oncology, this
      method of radiation delivery can have a favourable effect on several undesirable
      long-term side-effects that sometimes develop in children who receive
      radiotherapy, such as growth retardation and development of second primary
      tumours. Here, we describe the rationale for use of brachytherapy in children
      with cancer, the methods of the different brachytherapy techniques available, and
      the results obtained with several brachytherapy regimens in expert institutions
      throughout the world.

PMID- 16455481
TI  - Proteins with whey-acidic-protein motifs and cancer.
AB  - The importance of early diagnosis to reduce the morbidity and mortality from
      cancer has led to a search for new sensitive and specific tumour markers.
      Molecular techniques developed over the past few years allow simultaneous
      screening of thousands of genes, and have been applied to different cancers to
      identify many genes that are modulated in various cancers. Of these, attention
      has focused on genes coding for a family of proteins with whey-acidic-protein
      (WAP) motifs. Most notably, the genes coding for elafin, antileukoproteinase 1
      (previously called secretory leucocyte proteinase inhibitor, SLPI), WAP four
      disulphide core domain protein 1 (previously called prostate stromal protein 20
      kDa, PS20), and WAP four disulphide core domain protein 2 (previously called
      major human epididymis-specific protein E4, HE4), have been identified as
      candidate molecular markers for several cancers. In this review, we assess data
      for an association between cancer and human WAP proteins, and discuss their
      potential role in tumour progression. We also propose a new mechanism by which
      WAP proteins might have a role in carcinogenesis.

PMID- 16455482
TI  - Oral complications of radiotherapy.
AB  - Radiotherapy-induced damage in the oral mucosa is the result of the deleterious
      effects of radiation, not only on the oral mucosa itself but also on the adjacent
      salivary glands, bone, dentition, and masticatory musculature and apparatus.
      Biological response modifiers, cytoprotective drugs, salivary-sparing radiation
      techniques, and surgery have been introduced to combat and, more importantly, to
      prevent, the development of these complications. Radiotherapy-induced oral
      complications are complex, dynamic pathobiological processes that lower the
      quality of life and predispose patients to serious clinical disorders. Here, we
      focus on these oral complications of radiotherapy, highlight preventive and
      therapeutic developments, and review the current treatment options available for
      these disorders.

PMID- 16455483
TI  - Toxic epidermal necrolysis in patient with breast cancer receiving letrozole.

PMID- 16455484
TI  - Recall inflammatory skin reaction after use of pegylated liposomal doxorubicin in
      site of previous drug extravasation.

PMID- 16455485
TI  - Severe coagulopathy secondary to vitamin K deficiency in patient with small-bowel
      resection and rectal cancer.

PMID- 16455487
TI  - Mapping pathways and phenotypes by systematic gene overexpression.
AB  - Many disease states result from gene overexpression, often in a specific genetic
      context. To explore gene overexpression phenotypes systematically, we assembled
      an array of 5280 yeast strains, each containing an inducible copy of an S.
      cerevisiae gene, covering >80% of the genome. Approximately 15% of the
      overexpressed genes (769) reduced growth rate. This gene set was enriched for
      cell cycle-regulated genes, signaling molecules, and transcription factors.
      Overexpression of most toxic genes resulted in phenotypes different from known
      deletion mutant phenotypes, suggesting that overexpression phenotypes usually
      reflect a specific regulatory imbalance rather than disruption of protein complex
      stoichiometry. Global overexpression effects were also assayed in the context of
      a cyclin-dependent kinase mutant (pho85Delta). The resultant gene set was
      enriched for Pho85p targets and identified the yeast calcineurin-responsive
      transcription factor Crz1p as a substrate. Large-scale application of this
      approach should provide a strategy for identifying target molecules regulated by
      specific signaling pathways.

PMID- 16455486
TI  - p53 ubiquitination: Mdm2 and beyond.
AB  - Although early studies have suggested that the oncoprotein Mdm2 is the primary E3
      ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data
      suggests that p53 ubiquitination and degradation are more complex than once
      thought. The discoveries of MdmX, HAUSP, ARF, COP1, Pirh2, and ARF-BP1 continue
      to uncover the multiple facets of this pathway. There is no question that Mdm2
      plays a pivotal role in downregulating p53 activities in numerous cellular
      settings. Nevertheless, growing evidence challenges the conventional view that
      Mdm2 is essential for p53 turnover.

PMID- 16455488
TI  - Full-length myosin VI dimerizes and moves processively along actin filaments upon
      monomer clustering.
AB  - Myosin VI is a reverse direction actin-based motor capable of taking large steps
      (30-36 nm) when dimerized. However, all dimeric myosin VI molecules so far
      examined have included non-native coiled-coil sequences, and reports on full
      length myosin VI have failed to demonstrate the existence of dimers. Herein, we
      demonstrate that full-length myosin VI is capable of forming stable, processive
      dimers when monomers are clustered, which move up to 1-2 mum in approximately 30
      nm, hand-over-hand steps. Furthermore, we present data consistent with the
      monomers being prevented from dimerizing unless they are held in close proximity
      and that dimerization is somewhat inhibited by the cargo binding tail. A model
      thus emerges that cargo binding likely clusters and initiates dimerization of
      full-length myosin VI molecules. Although this mechanism has not been previously
      described for members of the myosin superfamily, it is somewhat analogous to the
      proposed mechanism of dimerization for the kinesin Unc104.

PMID- 16455489
TI  - The molecular basis of filamin binding to integrins and competition with talin.
AB  - The ability of adhesion receptors to transmit biochemical signals and mechanical
      force across cell membranes depends on interactions with the actin cytoskeleton.
      Filamins are large, actin-crosslinking proteins that connect multiple
      transmembrane and signaling proteins to the cytoskeleton. Here, we describe the
      high-resolution structure of an interface between filamin A and an integrin
      adhesion receptor. When bound, the integrin beta cytoplasmic tail forms an
      extended beta strand that interacts with beta strands C and D of the filamin
      immunoglobulin-like domain (IgFLN) 21. This interface is common to many
      integrins, and we suggest it is a prototype for other IgFLN domain interactions.
      Notably, the structurally defined filamin binding site overlaps with that of the
      integrin-regulator talin, and these proteins compete for binding to integrin
      tails, allowing integrin-filamin interactions to impact talin-dependent integrin
      activation. Phosphothreonine-mimicking mutations inhibit filamin, but not talin,
      binding, indicating that kinases may modulate this competition and provide
      additional means to control integrin functions.

PMID- 16455490
TI  - Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes.
AB  - Posttranslational modification with small ubiquitin-related modifier (SUMO) has
      emerged as a central regulatory mechanism of protein function. However, little is
      known about the regulation of sumoylation itself. It has been reported that it is
      increased after exposure to various stresses including strong oxidative stress.
      Conversely, we report that ROS (reactive oxygen species), at low concentrations,
      result in the rapid disappearance of most SUMO conjugates, including those of key
      transcription factors. This is due to direct and reversible inhibition of SUMO
      conjugating enzymes through the formation of (a) disulfide bond(s) involving the
      catalytic cysteines of the SUMO E1 subunit Uba2 and the E2-conjugating enzyme
      Ubc9. The same phenomenon is also observed in a physiological scenario of
      endogenous ROS production, the respiratory burst in macrophages. Thus, our
      findings add SUMO conjugating enzymes to the small list of specific direct
      effectors of H(2)O(2) and implicate ROS as key regulators of the sumoylation
      desumoylation equilibrium.

PMID- 16455491
TI  - Allosteric regulation of Hsp70 chaperones by a proline switch.
AB  - Crucial to the function of Hsp70 chaperones is the nucleotide-regulated
      transition between two conformational states, the ATP bound state with high
      association and dissociation rates for substrates and the ADP bound state with
      two and three orders of magnitude lower association and dissociation rates. The
      spontaneous transition between the two states is extremely slow, indicating a
      high energy barrier for the switch that regulates the transition. Here we provide
      evidence that a universally conserved proline in the ATPase domain constitutes
      the switch that assumes alternate conformations in response to ATP binding and
      hydrolysis. The conformation of the proline, acting through an invariant arginine
      as relay, determines and stabilizes the opened and closed conformation of the
      substrate binding domain and thereby regulates the chaperone activity of Hsp70.

PMID- 16455492
TI  - A uniform response to mismatches in codon-anticodon complexes ensures ribosomal
      fidelity.
AB  - Ribosomes take an active part in aminoacyl-tRNA selection by distinguishing
      correct and incorrect codon-anticodon pairs. Correct codon-anticodon complexes
      are recognized by a network of ribosome contacts that are specific for each
      position of the codon-anticodon duplex and involve A-minor RNA interactions.
      Here, we show by kinetic analysis that single mismatches at any position of the
      codon-anticodon complex result in slower forward reactions and a uniformly 1000
      fold faster dissociation of the tRNA from the ribosome. This suggests that high
      fidelity tRNA selection is achieved by a conformational switch of the decoding
      site between accepting and rejecting modes, regardless of the thermodynamic
      stability of the respective codon-anticodon complexes or their docking partners
      at the decoding site. The forward reactions on mismatched codons were
      particularly sensitive to the disruption of the A-minor interactions with 16S
      rRNA and determined the variations in the misreading efficiency of near-cognate
      codons.

PMID- 16455493
TI  - Nup-PI: the nucleopore-promoter interaction of genes in yeast.
AB  - Our previous work identified the inner basket of the NPC as a physical
      activation/protection station for force-tethered, epigenetically silenced genes.
      Here we show that a specific nucleopore-to-gene-promoter interaction (Nup-PI) is
      an early physiological event of gene activation. Nup-PI was discovered with
      chromatin endogenous cleavage (ChEC) experiments that mapped in vivo the genomic
      interaction sites of the nucleoporin Nup2p fused to microccocal nuclease (Nup2
      MN). Strong Nup-PI, cleavage by Nup2-MN, is observed at the promoters of the GAL
      genes and at HXK1 upon activation of these genes with galactose. Nup-PI at the
      GAL locus requires Gal4p and the UASg and TATA box elements but not SAGA and
      active transcription. The physical, activation-dependent interaction of the GAL
      locus with the NPC basket was confirmed by imaging. Chromosome-wide ChEC studies
      indicated that Nup-PI occurs at numerous genes. The data identify the NPC basket
      as a new, integral participant in gene expression.

PMID- 16455494
TI  - Combinatorial analysis of transcription factor partners reveals recruitment of c
      MYC to estrogen receptor-alpha responsive promoters.
AB  - In breast cancer and normal estrogen target tissues, estrogen receptor-alpha
      (ERalpha) signaling results in the establishment of spatiotemporal patterns of
      gene expression. Whereas primary target gene regulation by ERalpha involves
      recruitment of coregulatory proteins, coactivators, or corepressors, activation
      of these downstream promoters by receptor signaling may also involve partnership
      of ERalpha with other transcription factors. By using an integrated, genome-wide
      approach that involves ChIP-chip and computational modeling, we uncovered 13
      ERalpha-responsive promoters containing both ERalpha and c-MYC binding elements
      located within close proximity (13-214 bp) to each other. Estrogen stimulation
      enhanced the c-MYC-ERalpha interaction and facilitated the association of
      ERalpha, c-MYC, and the coactivator TRRAP with these estrogen-responsive
      promoters, resulting in chromatin remodeling and increased transcription. These
      results suggest that ERalpha and c-MYC physically interact to stabilize the
      ERalpha-coactivator complex, thereby permitting other signal transduction
      pathways to fine-tune estrogen-mediated signaling networks.

PMID- 16455495
TI  - Transcriptional activators are dispensable for transcription in the absence of
      Spt6-mediated chromatin reassembly of promoter regions.
AB  - The packaging of the eukaryotic genome into chromatin is likely to have a
      profound influence on transcription from the underlying genes. We have previously
      shown that the disassembly of promoter nucleosomes is obligatory for activation
      of the yeast PHO5 and PHO8 genes. Here, we show that the PHO5 promoter
      nucleosomes are reassembled concomitant with transcriptional repression and
      displacement of the TATA binding protein and RNA polymerase II (RNA Pol II). We
      identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome
      reassembly onto the PHO5, PHO8, ADH2, ADY2, and SUC2 promoters during
      transcriptional repression. Furthermore, promoter nucleosome reassembly is
      essential for transcriptional repression. In the absence of Spt6-mediated
      nucleosome reassembly, the activators Pho4 and Pho2 are displaced from the PHO5
      promoter in repressing conditions, yet transcription is sustained. As such, these
      studies demonstrate that activators are not required for transcription in the
      absence of competing chromatin reassembly.

PMID- 16455497
TI  - Human telomeres have different overhang sizes at leading versus lagging strands.
AB  - G-rich 3' telomeric overhangs are required both for forming the distinct telomere
      structures to protect chromosome ends and for extending telomeres by telomerase.
      However, little is known about the molecular mechanisms generating telomere
      overhangs in human cells. We show here that cultured normal human diploid cells
      have longer G overhangs at telomeres generated by lagging-strand synthesis than
      by leading-strand synthesis. We also demonstrate that telomerase expression
      results in elongated overhangs at the leading daughter telomeres. Thus, the
      overhangs at the leading and lagging daughter telomeres are generated differently
      in human cells, and telomerase may preferentially affect overhangs generated at
      the telomeres produced by leading-strand synthesis.

PMID- 16455496
TI  - Direct observation of DNA distortion by the RSC complex.
AB  - The Snf2 family represents a functionally diverse class of ATPase sharing the
      ability to modify DNA structure. Here, we use a magnetic trap and an atomic force
      microscope to monitor the activity of a member of this class: the RSC complex.
      This enzyme caused transient shortenings in DNA length involving translocation of
      typically 400 bp within 2 s, resulting in the formation of a loop whose size
      depended on both the force applied to the DNA and the ATP concentration. The
      majority of loops then decrease in size within a time similar to that with which
      they are formed, suggesting that the motor has the ability to reverse its
      direction. Loop formation was also associated with the generation of negative DNA
      supercoils. These observations support the idea that the ATPase motors of the
      Snf2 family of proteins act as DNA translocases specialized to generate transient
      distortions in DNA structure.

PMID- 16455498
TI  - Adenylation and exosome-mediated degradation of cotranscriptionally cleaved pre
      messenger RNA in human cells.
AB  - In humans, polyadenylation of messenger RNA (mRNA) protects transcripts from
      degradation and enhances translation efficiency. Conversely, in bacteria,
      polyadenylation destabilizes mRNA. RNA adenylation was recently implicated in
      promoting degradation of some yeast RNAs by the exosome. The exosome complex of
      exoribonucleases is a major degradation machine in eukaryotes, and many of its
      components share significant homology with bacterial exonucleases. The human beta
      globin pre-mRNA is cotranscriptionally cleaved within its 3' flank. Here, we show
      that some RNA ends, coinciding with these cotranscriptionally cleaved regions,
      contain short A tails on their 3' ends. Moreover, all of the pre-mRNA species
      detected accumulate in the absence of the exosome. We have also detected
      adenylation on RNA 3' ends originating within the mouse serum albumin (MSA) 3'
      flanking region RNA. This step in pre-mRNA degradation may represent an
      additional role for adenylation in mammals.

PMID- 16455499
TI  - Epirubicin-docetaxel in advanced gastric cancer: two phase II studies as second
      and first line treatment.
AB  - METHODS: We evaluated the Epitax combination (epirubicin 60 mg/m2 and docetaxel
      75 mg/m2, every 3 weeks) in advanced gastric cancer (AGC) as second-line
      treatment after fluorouracil and platinum in 50 patients, then as first-line
      treatment in 36 patients. We report here the results of these two phase II
      studies. RESULTS: In the second-line treatment, the response rate (RR) was 15.5%.
      Grade 3-4 neutropenia was observed in 68% (febrile neutropenia in 40%, one
      treatment-related death). Median time to progression (TTP) and overall survival
      (OS) were 2.4 and 5.0 months, respectively. In the first-line treatment, the RR
      was 19.4%. With prophylactic granulocyte colony-stimulating factor, grade 3-4
      neutropenia was reported in 38.9%. Then 22 patients received a second-line and 11
      patients a third-line treatment. Median TTP and OS were 4.5 and 12 months,
      respectively. CONCLUSION: Epitax showed moderate activity in AGC. RR in both
      trials suggests a non-cross resistance with fluorouracil/platinum combination.
      The 12-month OS in the first-line treatment could be partly explained by early
      evaluation and active non-cross resistant second-line therapy.

PMID- 16455500
TI  - [The frequency of cancer in France in year 2002, and trends since 1968].
AB  - The estimated number of cancers diagnosed in 2002 is 150,000 in the male
      population and 120,000 in the female population and there were close to 88,000
      cancer deaths among men and 59,000 cancer deaths among women in France. The most
      frequent cancer sites in the male population are prostate, lung, colon, intestine
      and head & neck (mouth, pharynx, larynx). In the female population, breast cancer
      is by far the most frequent cancer, followed by colorectal cancer. Between 1968
      and 2002, cancer mortality decreased by 5% for men and by 19% for women. Cancer
      mortality reached a maximum in 1987 in the male population and in the last 15
      years the decrease is larger among men than among women.

PMID- 16455501
TI  - [EGFR-targeted therapies: what's new?].
AB  - Anti-EGFR molecules with monoclonal antibodies or tyrosine protein kinase
      inhibitors represent a strategy which remains promising as targeted therapies of
      cancers, despite some ambiguous results. This review proposes to expose the state
      of the art concerning the development of anti-EGFR molecules: rationale of this
      approach, analysis of the results obtained on the one hand by monoclonal
      antibodies and on the other hand by tyrosine kinase inhibitors. Finally, a
      presentation is done about possible predictive factors for a relevant use of
      these molecules in the future.

PMID- 16455502
TI  - [PI3K-AKT-mTOR pathway inhibitors].
AB  - Molecular targeted agents have enlarged the armamentarium of anti-cancer
      therapies. Along with the success of some anti-growth factor receptors, signal
      transduction inhibitors represent a promising anti-cancer strategy. The PI3K-AKT
      mTOR pathway is a key pathway frequently altered in cancer cells. This manuscript
      provides an overview of the PI3K-AKT-mTOR pathway and its targeting in human
      malignancies. A focus is delivered for mTOR inhibitors.

PMID- 16455503
TI  - [Histone-deacetylases inhibitors: from TSA to SAHA].
AB  - Histone-deacetylase inhibitors (HDCACi) represent a new class of antitumor agents
      currently in clinical development. They target a family of enzymes which catalyse
      histone acetylation modifications, in particular for histones H2A, H2B, H3 and
      H4. These proteins stabilize the nucleosome core, fundamental unity of chromatin
      which represents the first level of DNA nuclear compaction. The balance of
      histone acetylation is maintained by histone-acetyltransferases (HAT) and histone
      deacetylases (HDAC) which play an important role in gene transcription.
      Alterations of HDACs were identified in tumor cells and contribute to the massive
      perturbations of gene expression in numerous tumors. HDAC inhibition leads to
      differentiation, cell cycle arrest and apoptosis in tumor cells. HDACi
      efficiently prevent tumor growth in a variety of in vivo preclinical models.
      Several structurally distinct classes of HDACi have entered in clinical trials
      and a significant antitumor activity was reported in several cases. However, a
      better understanding of the biological effects of this class of enzymes is
      mandatory for the successful development of these new antitumoral agents. In this
      review, are exposed the main drug candidates in clinical development. In the near
      future, it will be interesting to define direct relationships between specific
      inhibition of one or several HDAC and the subsequent HDAC-dependent antitumor
      effects to define a new generation of specific histone-deacetylase inhibitors.

PMID- 16455504
TI  - [Non-AIDS-defining malignancies in HIV patients: clinical features and
      perspectives].
AB  - Eventhough the advent of highly active antiretroviral therapy (HAART) has
      dramatically improved patient outcome and provided a significant shrinking of the
      cases and severity of opportunistic infections, AIDS malignancies have become
      responsible of a new vexing challenge in HIV patient care and cure. Indeed,
      malignant tumors currently rank among the leading cause of morbidity and
      mortality in patients infected with HIV. In addition to the AIDS-malignancies,
      non-AIDS defining tumors have a higher incidence than the general population such
      as Hodgkin disease, lung cancer, cutaneaous cancer and anal cancer. These
      malignant tumors are generally characterized by a more aggressive behaviour at
      diagnosis and a poorer outcome compared with the same tumors in the general
      population. Although recent therapeutic advances have been made in chemotherapy,
      combinations with antiretroviral agents, for many of these malignancies the
      pronostic remains poor and there is a deeply lack of current therapeutic
      guidelines for these cancer patients care and cure. These recommendations might
      be the fruit of a new networking between HIV specialists and oncologists and of
      an improving knowledge of the pathogenesis and clinical features of these AIDS
      non-defining tumors.

PMID- 16455505
TI  - [What is new in the surgical treatment of pelvic gynecologic cancers?].
AB  - General tendency of modern cancerology is the research of adequacy between extent
      of disease and treatments. This concept is of course valid for gynaecology and we
      saw these last months the promising results of fertility-sparing surgery: in
      initial cervical cancers and in ovarian cancer with good prognosis. Actual
      Studies should define a clear attitude in patient less than 40 with initial
      endometrial cancer. At the same time, the development of laparoscopic surgery has
      continued in cervical cancer staging. If use of sentinel node in endometrial or
      vulvar cancers remains discussed as for its reliability, importance of staging
      was stressed for cervical cancer and initial ovarian cancer. Laparoscopic surgery
      is confirmed in patient at risk with endometrial cancer but it is necessary to
      stress efforts of French teams which still push back the technical limits of
      laparoscopic approach like pelvic exenteration or intra-peritoneal
      chemohyperthermia in advanced ovarian cancer. The adventure continues....

PMID- 16455506
TI  - [Current trends in head and neck squamous cell carcinomas].
AB  - Squamous cell carcinomas of the head and neck remain frequent in France with an
      evolving epidemiology. Progress was observed both in diagnostic and treatments.
      Increasing possibilities of curative treatment should be provided within next
      years through surgery, radiotherapy, chemotherapy and target therapies as well as
      high performance imaging modalities and molecular biology and tumoral markers.
      Surgical techniques have improved function preservation while non surgical means
      have increased efficacy through chemo-radiotherapy. Assessment of optimal
      sequential therapeutic strategies is required, including both oncologic efficacy
      and quality of life.

PMID- 16455507
TI  - [Recent advances in digestive oncology (pancreas excluded)].
AB  - The present manuscript focus on new data regarding gastro-intestinal (GI) tumors
      (pancreas excluded). Two mains issues are discussed: advances in terms of the
      molecular basis of GI oncogenesis, and the data on molecular targeted agents for
      which the cost/efficacity balance needs to be addressed.

PMID- 16455508
TI  - [Pancreatic cancer: what is new in 2005?].
AB  - During the year 2005, many publications were presented about pancreatic tumours
      concerning the palliative treatment of advanced adenocarcinoma, perioperative
      strategies (i.e., adjuvant and neoadjuvant), and genetic or environmental factors
      that predispose to this cancer. Several valuable first lines of chemotherapy for
      unresectable cancers will be soon available, in view of promising results of
      biotherapies (i.e., erlotinib) or capecitabine combined with gemcitabine.
      Perioperative treatments may provide additional chances to cure the disease or to
      delay the tumor relapse. In addition, it should allow to better select the
      patients for a surgical resection (neoadjuvant strategy). About basic research,
      new developments of proteomic and pharmacogenomic are promising. Early detection
      of pancreatic adenocarcinoma in high-risk patients (about 10% of pancreatic
      adenocarcinomas), although delicate to perform, may become soon a reality in our
      practice. The deleterious role of tobacco consumption and way of feeding has been
      confirmed by several communications this year.

PMID- 16455509
TI  - [Update on cerebral tumors].
AB  - This review aims to discuss the main advances in gliomas, primary cerebral
      lymphomas and cerebral metastasis. The recent development of molecular biology
      and cerebral imaging allows a better understanding and management of gliomas and
      phase III studies have concluded to the benefit of adjuvant temozolomide
      administered during and after radiotherapy for glioblastomas: this strategy is
      yet to become a standard. Optimal treatment for primary central nervous system
      lymphoma remains to be defined, and several studies aims to precise the value of
      radiotherapy as consolidation treatment. Several trials reviewing the current
      treatment options for brain metastasis (whole brain radiation therapy, surgical
      resection stereotactic radiosurgery and chemotherapy) are highlighted.

PMID- 16455511
TI  - [New entities in pathological classification and new therapeutic options in renal
      cell carcinoma].
AB  - Therapy for renal cell carcinoma has made considerable progress in the past few
      years. The aims of this review are to update the pathological classification of
      this tumor and discuss predictive factors for tumor response and survival in the
      case of metastasis as well as the place of immunotherapy with interleukine-2
      and/or interferon alpha . Furthermore, we will review new therapeutic options and
      current results on allogeneic stem cell transplantation with non-myeloablative
      conditioning and HLA genoidentical donors. Finally, we will present targeted
      therapy (antiangiogenic drugs and tyrosine kinase inhibitors) with the mechanisms
      of action, efficacy and appropriate use in the treatment of metastatic renal cell
      carcinoma.

PMID- 16455510
TI  - [News of the year 2005 in sarcomas].
AB  - This year, the innovations were numerous in sarcomas. Important progress were
      accomplished in the search for predictive factors which make it possible to
      propose to the patient a personalized treatment with the therapeutic ones reduced
      in the event of good prognosis or on the contrary aggressive steps in the event
      of bad prognosis. These prognostic factors can be genetic or clinical. Progress
      were also accomplished in the clinical field with the research of the most
      adapted therapeutic strategies and of advanced in various drugs of chemotherapy
      in particular the ET-743. Lastly, research is active and of many ways are tested
      into preclinic with a detailed attention on the way of the angiogenesis.

PMID- 16455512
TI  - [Treatment of multiple myeloma].
AB  - Treatment of patients with multiple myeloma has shown considerable progress these
      last two decades. While autologous stem cell transplantation seems to be agreed
      as the "gold standard" of front-line treatment in the young patients, the result
      of IFM99-06 prospective study would probably lead to a change regarding treatment
      of elderly as patients who received the thalidomide-melphalan-prednison
      association had better overall survival than those who received either the
      standard melphalan-prednison association or an intensive treatment. The best
      innovative therapeutic concept is illustrated by the new molecules that target
      both the myeloma cells and the bone marrow microenvironment. Thus, thalidomide
      and derivatives (Revlimid and the Actimid) and Velcade have transformed
      considerably the history of multiple myeloma. They have not to be considered as
      competitors but rather complementary whose impact will probably come of their
      combination and their association with the intensive treatments. The issues of
      maintenance therapy and allogeneic stem cell transplantation in the treatment of
      patients with myeloma remain to be addressed.

PMID- 16455514
TI  - [What's new in geriatric oncology?].
AB  - Remarkably, although 60% of new cancer cases and over 70% of cancer deaths occur
      in patients aged 65 years and older in Europe, standard treatment strategies have
      been mostly validated in younger adults. This demographic trend has led to the
      emergence of a new medical discipline, geriatric oncology and the development
      worldwide of geriatric oncology programs for the individualized management of
      elderly cancer patients. Elderly cancer patients represent an increasing share of
      the population and strategies for treating cancer must evolve to face this
      ineluctable reality. Treatment should take into account the highly heterogeneous
      physiological age of the elderly, their individual life expectancy, functional
      reserves, social support and preferences. French geriatric oncology programs have
      been mostly based on the interdependence of geriatricians, oncologists and
      auxiliary nursing people. This approach represent the best way to offer patients
      optimal management; oncologists and geriatricians collaborate to assess both
      global health status by means of Comprehensive Geriatric Assessment (CGA) and
      tumor stage by means of Comprehensive Tumor Assessment (CTA) and to initiate
      individualized care plans, involving comprehensive management and follow-up of
      all identified problems. This paper focuses on progress observed in the field of
      geriatric oncology both in France and worldwide.

PMID- 16455513
TI  - [Monoclonal antibodies for lymphomas and leukemias in 2005].
AB  - Advances in the development of monoclonal antibody (MAb) have proven major
      benefice in the treatment of hematologic malignancies. Phase II studies showed
      similar results than classical chemotherapy in refractory or relapsed patients,
      with less toxicity in heavily pre-treated population. Moreover, MAb enhanced
      sensitivity to chemotherapy. Combined treatments resulted in an increase of
      global response and complete remission in non previously pre-treated patients
      with follicular lymphoma, diffuse large cell lymphoma and chronic lymphocytic
      leukemia. Recently, the association of anti-CD20 and 131Iode was shown to be
      efficient in follicular lymphomas. The benefits of MAb is less clear in myeloid
      malignancies. The role of MAb in the treatment of myelodysplastic syndrome
      remains uncertain although the use of anti-CD33 in acute myeloid leukemias is
      promising. The aim of this review is to present an updated overview of the most
      used MAb in the treatment of leukemias and lymphomas not involving bone marrow
      transplantation.

PMID- 16455515
TI  - [What is new in brachytherapy?].
AB  - The brachytherapy was used as of the discovery of the radioactivity and became a
      modern method of conformational irradiation using high technology. Every year, 8
      10,000 treatments are delivered, which represents 5% of the total number of
      irradiations in France. Its revival comes from its increasing use in the
      treatment of localised cancers of the prostate of favourable prognosis, because
      of its effectiveness comparable with that of the surgery or the external
      radiotherapy, its very good immediate tolerance and its better preservation of
      the erectile function. In 2005, more of 1000 patients were treated in France,
      number that should quickly rise. The gynecological brachytherapy remains
      essential in the treatment of the invasive cancers of the uterine cervix. It
      profits of the progress of the imagery and in the optimisation of the calculation
      of the dose distribution allowing the optimisation of the irradiation by means of
      stepping source afterloaders (pulsed brachytherapy). The brachytherapy in head
      and neck keeps its indications, especially in the exclusive or postoperative
      irradiation of the cancers of the oral cavity or of the oropharynx. In the
      treatment of the breast cancer, a new position for the modern brachytherapy
      should be occur with the concepts of brachytherapy boost. Lastly, many precise
      indications are always of topicality. Thus, the brachytherapy by permanent
      implants, at low dose rate, high dose rate or pulsed dose rate, associated to the
      tools of imagery, of optimisation and technologies of stepping source
      afterloaders is competing or complementary with new 3D or 4D techniques of three
      or four dimensional irradiation.

PMID- 16455516
TI  - [Refusing treatment: patient responsibility and autonomy. About a French National
      Consultative Ethics Committee statement(no 87, April 2005)].
AB  - A recent French National Consultative Ethics Committee statement confirms that
      medical doctors are required by law to accept a patient's refusal of treatment,
      even if the consequence is the loss of chances of being cured. This refusal
      raises difficult clinical and ethical issues. Respecting a patient's decision is
      only valid when he/she is fully responsible, able to understand the proposed
      treatments and the consequences of his/her refusal, uninfluenced by friends and
      relatives, ignorance, disarray, an excessively pessimistic appraisal of the
      situation, a conflict with the doctors or with medicine. Doctors must avoid
      passively accepting a refusal without discussion but must also avoid paternalism
      or moral pressure. Adequate mutual knowledge of the way they think, their values
      and their objectives helps to maintain mutual respect and confidence in the
      patient-doctor relationship: the doctor is not a "supertechnician" nor is the
      patient a treatment consumer. Information, knowledge of the possibilities and
      limits of current medicine and of patients'complex, conscious and unconscious
      motives (which justifies the psycho-oncologist's role), recommendations of
      medical societies, experience of difficult ethical issues help to avoid
      unauthentic refusals, conflicts and staff burnout.

PMID- 16455518
TI  - Cellular dynamics of small RNAs.
AB  - This review highlights the unexpectedly complicated nuclear egress and nuclear
      import of small RNAs. Although nucleus/cytoplasm trafficking was thought to be
      restricted to snRNAs of many, but not all, eukaryotes, recent data indicate that
      such traffic may be more common than previously appreciated. First, in conflict
      with numerous previous reports, new information indicates that Saccharomyces
      cerevisiae snRNAs may cycle between the nucleus and the cytoplasm. Second, recent
      studies also provide evidence that other small RNAs that function exclusively in
      the nucleus-the budding yeast telomerase RNA and possibly small nucleolar RNAs
      may exit to the cytoplasm, only to return to the nucleus. Third,
      nucleus/cytoplasm cycling of RNAs also occurs for RNAs that function solely in
      the cytoplasm, as it has been discovered that cytoplasmic tRNAs of budding yeast
      travel "retrograde" to the nucleus and, perhaps, back again to the cytoplasm to
      function in protein synthesis. Fourth, there is at least one example in ciliates
      of small double-stranded RNAs traveling multiple cycles between the cytoplasm and
      distinct nuclei to direct genome structure. This report discusses data that
      support or argue against nucleus/cytoplasm bidirectional movement for each
      category of small RNA and the possible roles that such movement may serve.

PMID- 16455519
TI  - The diverse biological functions of phosphatidylinositol transfer proteins in
      eukaryotes.
AB  - Phosphatidylinositol/phosphatidylcholine transfer proteins (PITPs) remain largely
      functionally uncharacterized, despite the fact that they are highly conserved and
      are found in all eukaryotic cells thus far examined by biochemical or sequence
      analysis approaches. The available data indicate a role for PITPs in regulating
      specific interfaces between lipid-signaling and cellular function. In this
      regard, a role for PITPs in controlling specific membrane trafficking events is
      emerging as a common functional theme. However, the mechanisms by which PITPs
      regulate lipid-signaling and membrane-trafficking functions remain unresolved.
      Specific PITP dysfunctions are now linked to neurodegenerative and intestinal
      malabsorption diseases in mammals, to stress response and developmental
      regulation in higher plants, and to previously uncharacterized pathways for
      regulating membrane trafficking in yeast and higher eukaryotes, making it clear
      that PITPs are integral parts of a highly conserved signal transduction strategy
      in eukaryotes. Herein, we review recent progress in deciphering the biological
      functions of PITPs, and discuss some of the open questions that remain.

PMID- 16455520
TI  - Dealing with dysfunctional doctors. The Society of British Neurological Surgeons'
      response to the Chief Medical Officer's 'Call for Ideas'.

PMID- 16455522
TI  - Angiography postclipping and coiling of cerebral aneurysms.
AB  - Postclipping cerebral angiography is generally not practised in the UK. The
      International Subarachnoid Trial (ISAT) data show that coiling compared
      favourably with clipping in the early posttreatment phase. We present a 4-year,
      single unit experience comparing cerebral angiography at 6 months postclipping
      and postcoiling, defining the proportion of aneurysms in either group, which were
      incompletely excluded from the cerebral circulation after treatment. There were 4
      'dog-ear' remnants (4.6%) in the clipping group of 86 aneurysms, one of which
      required further surgery. Thirty-one out of 82 (37.8%) coiled aneurysms that
      underwent check angiography were inadequately excluded from the cerebral
      circulation at 6 months. Of these, to date, four patients have undergone re
      coiling. Although the immediate complications of coiling may be less than those
      of clipping (ISAT), it seems that the degree and permanence of exclusion of an
      aneurysm from the cerebral circulation may be more secure with surgery. In
      summary, the rates of incomplete aneurysmal exclusion from the cerebral
      circulation, the requirement for reintervention and the requirement for
      continuing surveillance were all higher in the coiled population than in the
      clipped population.

PMID- 16455521
TI  - The neuropsychology of normal pressure hydrocephalus (NPH).
AB  - Normal pressure hydrocephalus (NPH) accounts for one of the few known forms of
      reversible dementia. Varied aetiology and clinical presentation contribute to
      difficulties with early or differential diagnoses, and delayed surgical treatment
      may be less efficacious. Clinical neuropsychology provides a means of determining
      a cognitive profile for NPH, assisting in differential diagnosis, tracking the
      disorder's progression and assessing the efficacy of treatment. This article will
      review possible applications of clinical neuropsychology and propose a clinical
      assessment protocol for NPH.

PMID- 16455523
TI  - A comparative study of referral patterns and management of patients with
      malignant brain tumours in Birmingham, UK, and Toronto, Canada.
AB  - The management of malignant brain tumours comprises a huge financial burden to
      any health care system. The referral pattern and initial management of this
      condition has not been widely investigated. Our main aim was to investigate and
      compare the referral patterns between two tertiary referral centres in
      Birmingham, UK, and Toronto, Canada, which have similar health care provision
      structures, but different financial resources, in order to examine whether there
      are any significant delays in the pathway of either system. The investigation
      consisted of a retrospective analysis of case records of patients identified as
      having malignant brain tumours who had been operated on at the two centres during
      the period 1997-1998. Data were collected on patient demographics, symptomatology
      at presentation, referral pattern, and time intervals between presentation,
      investigations, neurosurgical consultation and operation. Mann-Whitney U-tests of
      statistical significance were used to compare the two centres. Sixty-eight and
      100 patients in Birmingham and Toronto, respectively, were identified from the
      registers following exclusion of patients with benign or low-grade tumours. Both
      centres were found to be similar with respect to sociodemographic factors of
      patients with malignant brain tumours. Referral patterns were analysed for
      presenting symptoms of neurological deficit and seizure, and found to be similar
      for both centres. Time intervals from presentation to investigation and from
      investigation to neurosurgical consultation were not significantly different
      between the two centres. Significant differences were found from neurosurgical
      consultation to operation (Birmingham, 3 days, and Toronto, 6 days, p = 0.006),
      and the duration of stay in hospital (Birmingham, 11 days, and Toronto, 2 days, p
      < 0.001). Although there are differences in the financial resources of the two
      tertiary centres our study reveals no significant differences in the referral
      pathway to operation.

PMID- 16455524
TI  - Brucellar spinal epidural abscesses. Analysis of eleven cases.
AB  - Brucellar spinal epidural abscesses (BSEA) are rare and very few series of them
      have been reported. In order to evaluate the clinical characteristics, management
      and outcome of this entity, the clinical records and current status of a series
      of 11 patients have been retrospectively reviewed. A series of 11 patients
      treated for BSEA in our Service during a period of 12 years (1989-2000) have been
      retrospectively studied. Spinal epidural abscesses (SEA) were diagnosed by MRI,
      CT or at surgery. Brucellar aetiology of SEA was considered when
      seroagglutination tests were positive at a titre of 1/160 or higher, and/or
      Brucella spp. were isolated in the blood or sample cultures. Ten of the 11 cases
      were treated with rifampicin plus doxycycline and in the remaining patient
      streptomycin was added because of a poor initial response. Six patients underwent
      surgical decompression and debridement of the SEA. Outcome was excellent in nine
      cases and good in two. There was no mortality and only one patient recovered
      incompletely from preadmission neurological deficits. Although BSEA is considered
      to be an unusual complication of spondylitis, our findings show that in some
      cases it can follow direct haematogenous spread to the extradural space. Surgical
      treatment must be undertaken when major neurological deficits are present. If
      antibiotic treatment is chosen as the initial therapy, the possibility of sudden
      neurological deterioration must be taken into account. Contrary to the high morbi
      mortality rates reported in pyogenic or tuberculous SEA, BSEA has a good
      prognosis with early diagnosis and appropriate management.

PMID- 16455525
TI  - Intracranial falcine and convexity chondromas: two case reports.
AB  - Intracranial chondromas are uncommon intracranial tumours that most frequently
      arise from the skull base. They can, however, arise from the calvarium or the
      meninges. In these cases their neuroradiological features may mimic other
      intracranial tumours. We present two cases of intracranial chondroma, one that
      originated from the convexity and the other from the falx. Total excision was
      achieved in both cases. The literature on intracranial chondromas is reviewed.

PMID- 16455526
TI  - Intraosseous schwannoma of the cervical spine.
AB  - The authors report a rare case of a cervical intraosseous schwannoma, which was
      diagnosed following an incidental history of trauma. This is the first case of an
      intraosseous schwannoma of the cervical vertebra that was diagnosed using
      magnetic resonance imaging. The authors discuss the radiological imaging,
      surgical procedure and review the relevant literature.

PMID- 16455528
TI  - Ruptured aneurysm at the choroidal branch of the posterior inferior cerebellar
      artery: a case report, review of the literature and proposed pathogenesis.
AB  - Aneurysms rarely occur at the choroidal branch of the posterior inferior
      cerebellar artery (PICA) and their pathogenesis is not well understood. We report
      such a case and review the literature. A 69-year-old female was admitted for a
      sudden onset of severe headache with nausea and vomiting. Soon after arrival, she
      became less responsive. CT of the head revealed an intraventricular haemorrhage
      (IVH) predominantly in the fourth and third ventricles without subarachnoid
      hemorrhage and associated with hydrocephalus. Cerebral angiography demonstrated
      an aneurysm at the choroidal branch of the PICA. The aneurysm was resected
      through a bilateral suboccipital craniotomy. The patient made a remarkable
      recovery. The literature describes five other cases of aneurysms arising from a
      choroidal branch of the PICA. Hypertension was a common finding in this
      population. In summary, aneurysms arising from a choroidal branch of the PICA are
      rare. Hypertensive vessel damage might be a major factor in their pathogenesis.
      We propose that the rupture of a hypertensive aneurysm might account for some
      isolated spontaneous IVH.

PMID- 16455529
TI  - Cervical intra-/extramedullary solitary fibrous tumour.
AB  - A 53-year-old man presented with a 9-month history of symptoms of right-sided
      weakness, tingling and hypersentivity to clothes on both sides of the body. MRI
      revealed a large intraspinal intradural tumour at the level of C3-C4 in the
      cervical cord. The final histology was a solitary fibrous tumour (SFT) of the
      cervical spinal cord. The radiological diagnosis, surgical management and
      histology are reviewed.

PMID- 16455527
TI  - Painful third nerve palsy in a patient with perimesencephalic subarachnoid
      haemorrhage.
AB  - A patient with perimesencephalic subarachnoid haemorrhage (PMSAH) developed a
      delayed third nerve palsy. Three formal cerebral angiograms, a computed
      tomography cerebral angiogram and a magnetic resonance angiogram all failed to
      reveal a vascular abnormality. Further investigations did not show any medical
      cause for the palsy. This appears to be the first case report of a patient with
      PMSAH presenting with a painful third nerve palsy.

PMID- 16455530
TI  - Acute haemorrhage into a microcystic meningioma leading to cerebral herniation.
AB  - Low-grade (WHO level I) meningiomas are slow-growing, benign tumours typically
      presenting with unspecific symptoms (e.g. headache), seizures, cranial nerve
      compression and neuropsychological symptoms determined by location and size of
      the lesion. Haemorrhagic onset and sequelae are rare, and have been described
      infrequently. This is a case of a 50-year-old male presenting with signs of
      tentorial herniation secondary to hyperacute intratumoural haemorrhage (ITH) into
      a previously undiagnosed meningioma. Emergency surgical decompression and
      exstirpation of the lesion helped to achieve a favourable outcome. ITH has been
      described in all including benign intracranial neoplasms. Factors associated with
      a higher risk for haemorrhage in meningiomas are discussed. Though haemorrhages
      associated with meningiomas have been reported, ITH into low-grade meningiomas
      leading to herniation remains a rarity. Bearers of known lesions and their
      treating physicians who opt for conservative or delayed treatment should be aware
      of this remote complication.

PMID- 16455531
TI  - Idiopathic spinal epidural lipomatosis.
AB  - We report a rare case of paraparesis caused by thoracic spinal epidural
      lipomatosis in a female patient who did not have any recognized predisposing
      factor for this condition.

PMID- 16455534
TI  - Cauda equina syndrome: the timing of surgery probably does influence outcome.

PMID- 16455536
TI  - Vestibular schwannoma management: What is the 'best' option?
AB  - There is an abundance of medical literature describing the management options for
      vestibular schwannomas. However, the lack of high quality clinical trials means
      that, for any individual patient, the decision is often based on the clinician's
      personal biases. The management options that are available are conservative
      treatment, surgery, single-dose stereotactic radiosurgery and fractionated
      radiotherapy. In this review, we set out what the aims of managing a vestibular
      schwannoma should be and compare how these different treatment modalities
      perform. The particular objectives of tumour control, cranial nerve preservation,
      prevention of malignancy, quality of life and cost-effectiveness are discussed.
      It remains difficult to differentiate between these methods when more than one is
      suitable; the literature confirms that they are all safe and effective, but the
      decision must be the patient's, based on their individual priorities. This review
      should equip the clinician to provide an informed overview of the options.

PMID- 16455537
TI  - Polymorphism of the heme oxygenase-1 gene and cerebral aneurysms.
AB  - Inflammation is thought to play an important role in intracranial aneurysm
      formation. Heme-oxygenase-1(HO-1) is a novel anti-inflammatory factor. A length
      polymorphic variant of the HO-1 gene promoter region, comprising (GT)n
      dinucleotide repeats, is associated with altered levels of gene transcription:
      long (= 36 GT) repeats are associated with decreased HO-1. We hypothesized that
      patients with aneurysmal subarachnoid haemorrhage were more likely to have long
      repeats than controls. Sixty-nine patients with aneurysms and 230 age-matched
      controls were genotyped, and allelic repeats were classed as <36 (short and
      medium repeats) and >36 (long repeats). Patients were more likely to have =36
      repeats than controls (8 v. 4%, p = 0.037. Control patients without aneurysms
      were more likely to have short alleles. Thus, facilitated up-regulation of HO-1
      may be a protective anti-inflammatory factor against the development of
      intracranial aneurysms, whilst a propensity to a more pro-inflammatory state may
      put individuals at risk. However, because of the relatively small sample size and
      modest statistical significance, the data must be interpreted with caution and
      the association needs to be confirmed in further samples.

PMID- 16455538
TI  - Study of correlation between expression of bradykinin B2 receptor and
      pathological grade in human gliomas.
AB  - In clinical practice there is a difference in response of the blood-tumour
      barrier (BTB) permeability induced by bradykinin in brain tumours with the same
      pathology. The variability in response of tumours to bradykinin is likely to be
      related to the expression level of bradykinin B(2) receptor. This study used
      fresh human glioma samples to determine the expression level of bradykinin B(2)
      receptor on gliomas with different pathological grades. The grade of tumour was
      classified using the WHO classification. To determine the bradykinin B(2)
      receptor expression level in gliomas, Immunohistochemistry and Western blot
      methods were used. In 24 cases of gliomas there were eight cases of WHO I glioma,
      eight cases of WHO II glioma and eight cases of WHO III glioma. Both Western blot
      and immunohistochemistry showed bradykinin B(2) receptors localized on tumour
      cells, whilst brain cells at the edge of the glioma hardly expressed B(2)
      receptor. There were significant differences of bradykinin B(2) receptor
      expression level among different pathological grades of glioma. The expression of
      B(2) receptor in the three grades of glioma was in the order of WHO I < WHO II <
      WHO III. Determination of bradykinin B(2) receptor expression level in human
      glioma may be useful in screening glioma patients to predict whether they will be
      suitable for opening of the blood - tumour barrier with bradykinin or its
      analogue.

PMID- 16455539
TI  - Non-surgical primary treatment of chronic subdural haematoma: Preliminary results
      of using dexamethasone.
AB  - From a series of 112 cases (64 men and 48 women, aged 37 - 91 years) of chronic
      subdural haematoma (CSDH) in a 2-year period from January 1998 to December 1999,
      we have prospectively studied a group of 30 patients, who were managed non
      operatively: 26 patients were treated with dexamethasone (Group 1) and four
      patients expectantly (Group 4). Nineteen patients (73%) from Group 1 were
      confused or had focal neurological deficits on admission. The mean maximum
      thickness of the CSDH was 12 mm. Only one of these cases (4%) required surgical
      drainage 6 weeks after steroid therapy. One patient died of an unrelated stroke
      (mortality = 4%). Two patients (8%) were left severely disabled. No significant
      complication from steroid therapy was documented. Out of the 85 surgically
      treated patients, 69 patients underwent surgical drainage in addition to steroid
      therapy (Group 2). Thirteen patients were treated with burr-hole drainage only
      (Group 3). The mean maximum thickness of the CSDH for these two groups were both
      16 mm. Comparing with group 1, the redrainage rate of Group 2 [4% (3/69, p = 1)]
      and that of Group 3 [15% (2/13, p = 0.253)] were not significantly different. 50%
      of patients in Group 4 (2/4, p = 0.039) required delayed surgical drainage. The
      mortality rates of Groups 2, 3 and 4 were 3% (2/69, p = 1), 15% (2/13, p = 0.253)
      and 50% (2/4, p = 0.039), respectively. Our results suggest that steroid
      treatment in a selected group of patients is a good option, particularly in
      patients with co-morbidity.

PMID- 16455540
TI  - The two-week waiting time standard for cancer: a neurosurgical perspective.
AB  - The implementation of the two-week wait initiative for cancer referrals in the
      NHS has had a major impact on outpatient services. A low clinical detection rate
      among GPs for neurological cancer has resulted in a large number of urgent
      referrals with a low yield of positive diagnoses. We have devised a strategy for
      minimizing the impact on outpatient clinics: patients are scanned prior to
      clinical review and those with normal scans are referred back to the GP without a
      clinic appointment. Out of 69 referrals of suspected CNS cancer made in 2003, 61
      were scanned and six resulted in a positive diagnosis. The equivalent of 10
      clinics was saved, and an increased speed of diagnosis and treatment was achieved
      with no compromise in patient care. Our study illustrates the consequences of the
      2-week wait initiative on the neurosurgical service, and proposes an effective
      and safe solution.

PMID- 16455542
TI  - Intramedullary capillary haemangioma.
AB  - Intramedullary capillary haemangioma is extremely rare and only four cases have
      been previously reported. We describe a further case, outlining the clinical,
      radiological, surgical and pathological features.

PMID- 16455541
TI  - Minimally invasive biopsy of parasellar lesions: safety and clinical applications
      of the endoscopic, transnasal approach.
AB  - The base of the skull can be affected by a variety of tumours requiring a wide
      range of treatment modalities. In formulating a management plan, histological
      diagnosis can play an essential role. Existing methods of skull base biopsy,
      especially in the anatomically critical parasellar region, include either
      prolonged open skull base approaches or image-guided needle biopsies. The latter
      methods can be time-consuming and cannot reliably avoid surrounding critical
      neurovascular structures. The experience with an endoscopic, transnasal biopsy of
      parasellar tumours in selected patients is presented. A preliminary series of 11
      patients harbouring parasellar lesions with some degree of extension to the
      sphenoid or maxillary sinus underwent endoscopic, transnasal biopsy. The
      procedure was diagnostic in all cases. There was no operative mortality and
      minimal morbidity only recorded. The biopsy results affected the patients'
      management and, based on these results, major skull base surgery was avoided in
      four cases. Direct endoscopic visualization prompted avoidance of a vascular
      catastrophe of an atypical vascular lesion. The endoscopic, transnasal biopsy
      appears to offer a number of advantages over existing methods in selected
      patients. It is minimally invasive as it employs the use of natural osseous
      corridors. Tissue sampling under direct visualization minimizes the risks of
      negative biopsies or damage to critical neurovascular structures. The use of
      additional imaging employed by image-guided needle biopsies in not necessary.
      When planning treatment of parasellar tumours, the endoscopic, transnasal route
      should be considered.

PMID- 16455543
TI  - Extra-cranial metastasis of glioblastoma multiforme presenting as acute
      parotitis.
AB  - We present an unusual case of extracranial metastasis of glioblastoma multiforme
      (GBM) to the parotid gland and cervical lymph nodes. The patient had previously
      undergone two craniotomies to debulk a left frontal GBM, followed by
      radiotherapy. After the second craniotomy, while waiting for chemotherapy, the
      patient was re-admitted with a short history of a painful swelling of his left
      parotid gland. The initial diagnosis was infective parotitis; however, as there
      was no improvement with broad-spectrum antibiotics, CT was undertaken, which
      revealed a mass in the parotid gland with a necrotic centre and enlarged cervical
      lymph nodes. Parotid gland biopsy revealed a parotid GBM metastasis. This case
      illustrates how GBM behaves in an aggressive manner even outside the CNS. A brief
      review of the literature and of the theories, which might explain the extra
      neural metastasis of this tumour is also presented.

PMID- 16455544
TI  - Subgaleal suction drain leading to fatal sagittal sinus haemorrhage.
AB  - The use of wound drains in surgical practice, very often falls into the realm of
      habit, rather than science. The utility of a prophylactic drain in surgical
      wounds may be questionable, but this practice is not uncommon, despite
      complications. We report a case of fatal haemorrhage from the superior sagittal
      sinus, due to a closed negative suction drain of the craniotomy wound in an
      infant operated upon for a growing fracture skull.

PMID- 16455545
TI  - Shoulder tip pain: an under-reported complication of ventriculoperitoneal shunt.
AB  - Ventriculoperitoneal (VP) shunt insertion is the commonest form of treatment for
      hydrocephalus. Shoulder tip pain after VP shunt insertion is unusual and has only
      recently been reported. We present a case of excruciating shoulder tip pain due
      to diaphragmatic irritation after VP shunt insertion.

PMID- 16455546
TI  - Myxopapillary ependymoma with intracranial metastases.
AB  - We report spontaneous seeding within the subarachnoid space from a myxopapillary
      ependymoma that progressed despite surgery and radiotherapy treatment.

PMID- 16455547
TI  - Peduncular hallucinations following subarachnoid haemorrhage.
AB  - We describe the case of a 56-year-old woman who suffered vivid visual
      hallucination following subarachnoid haemorrhage (SAH). These occurred from day 9
      to day 28 after the haemorrhage. An association with sleep disturbance, clinical
      findings, and the nature of the hallucinations suggested peduncular hallucinosis.
      Putative mechanisms in this case are discussed.

PMID- 16455548
TI  - Cowden's syndrome with Lhermitte-Duclos disease.
AB  - Cowden's syndrome (CS) is a rare autosomal dominant condition featuring multiple
      hamartomas, often with mucocutaneous lesions, goitre, breast cancer,
      gastrointestinal polyps or even Lhermitte-Duclos disease (LDD). In this article
      we report the case of a 34-year-old man who was diagnosed with LDD. Subsequent
      examinations also revealed manifestations of CS, i.e. macrocephaly, thyroid
      nodules and gastrointestinal polyps.

PMID- 16455549
TI  - Acute bleeding into the dural-outer membrane space after burr hole drainage for
      chronic subdural haemorrhage.

PMID- 16455550
TI  - Simultaneous presentation of meningiomas with other intracranial tumours.
AB  - Fifteen patients with simultaneous presentation of meningiomas with other
      intracranial tumours are reviewed. The associated tumours included a brain
      metastasis in six cases, glioma in three, pituitary adenoma in two,
      craniopharyngioma in one,acoustic schwannoma in two and brain lymphoma in one. A
      correct preoperative radiological diagnosis was made in 12 patients; in three
      others the associated tumour was discovered at operation and by histological
      studies. A one-stage removal of both tumours through the same approach was
      performed in nine patients, whereas six others underwent two-stage operations
      with an interval of 1 - 13 months. The literature relating to meningiomas
      associated with other intracranial tumours is reviewed and the possible
      pathogenetic correlations are discussed. A diagnostic pitfall may occur for
      metastasis into a meningioma, glioma surrounding a meningioma and different
      suprasellar lesions. The surgical indication and management of meningiomas may be
      significantly influenced by the presence of another different intracranial
      tumour.

PMID- 16455559
TI  - Spontaneous subarachnoid haemorrhage in the era of transition from surgery to
      embolization. A study of the overall outcome.
AB  - The aim of the investigation was to evaluate the outcome of spontaneous
      subarachnoid haemorrhage, in the era of new techniques, patient centralization
      and subspecialization, by taking into account the local conditions in Greece. A
      prospective observational study was conducted during a 4-year period. All
      patients with a first-ever spontaneous subarachnoid haemorrhage were enrolled.
      Clinical, management and outcome data were recorded. Two-hundred-and-eighteen
      consecutive patients with an 81% good, medium clinical grade (Hunt & Hess I-III)
      were identified. Rebleed and rebleed leading to death rates were 22 and 11%,
      respectively. Permanent deficit or death from vasospasm was 15%. Twenty-eight per
      cent of the study population died early, were unsuitable for further management
      (poor clinical status, advanced age) or declined angiography or treatment, and
      another 22% had a negative angiogram. The remaining 50% underwent intervention
      (neurosurgical/endovascular), for obliteration of an aneurysm. The overall
      favourable 6-month outcome was 59%, whereas the favourable outcome of the
      intervention group was 70%. Our results confirm the findings of previous series.
      The relatively worse results are due to delayed referral, and lack of
      availability of surgical or endovascular management in the early post-haemorrhage
      period (28% of the patients), particularly in potentially salvageable cases. On
      the basis of these observations, we recommend early intervention (surgery or
      embolization) and centralization/subspecialization, in order to improve the
      outcome.

PMID- 16455560
TI  - Bedside monitoring of CBF with xenon-CT and a mobile scanner: a novel method in
      neurointensive care.
AB  - Combining previously independently established techniques our objective was to
      develop and evaluate a method for bedside qualitative assessment of cerebral
      blood flow in neurointensive care (NICU) patients. The CT-protocol was optimized
      using phantoms and comparing a mobile CT-scanner (Tomoscan-M, Philips) with two
      stationary CT scanners. Thirty-two per cent xenon was delivered with standard
      equipment (Enhancer 3000). Mean cortical flow in volunteers was 48 ml/min/100 g,
      with the mean vascular territorial flow varying between 45 and 66 ml/min/100 g.
      The potential clinical usefulness was illustrated in three patients with
      vasospasm following subarachnoid haemorrhage. Our conclusion is that quantitative
      bedside measurements of CBF can be repeatedly performed in an easy and safe way
      in a standard NICU-setting, using xenon-inhalation and a mobile CT-scanner. The
      method is useful for the decision-making, and is a good example of how the
      quality of multi-modality monitoring in the NICU can be developed and further
      diversified.

PMID- 16455562
TI  - Selective vestibular neurotomy for Meniere's disease: a neurosurgical procedure?
AB  - The objective of this paper is to report the authors' experience with a 1.5-cm
      suboccipital craniotomy for selective vestibular neurotomy. Data were collected
      on 19 consecutive patients undergoing selective vestibular neurotomy for
      Meniere's disease, between June 1988 and January 2004, performed by a
      neurosurgeon. There were 10 males and nine females. Ages ranged from 35 to 69
      years (median 55). All patients had preoperative imaging, audiometric and caloric
      assessments. Patients were assessed postoperatively for residual vertigo and
      surgical complications. All patients had repeat audiometric and caloric
      evaluation postoperatively. Ten patients had excellent (mild residual deafness,
      no vertigo) and nine had good (no vertigo attacks, mild postural dizziness)
      results. Hearing was preserved at preoperative levels in 18 patients and improved
      in one patient. There were two CSF leaks--one settled with lumbar drainage and
      the other required wound re-exploration. Two patients developed transient facial
      weakness. There were no deaths. Selective vestibular neurotomy can be performed
      through a 1.5-cm suboccipital craniotomy without the need for an endoscope. It is
      a simple, safe and highly successful procedure for controlling vertigo attacks in
      intractable Meniere's disease. This procedure preserves hearing and should be
      considered for those refractory to medical treatments.

PMID- 16455561
TI  - Consideration of ergonomic aspects in the development of a new endoscopic
      navigation system.
AB  - During the development of new navigation systems, the ergonomic aspects of the
      accompanying software are seldom taken into account. The VN system is a
      navigation system working with real and previously stored neuroendoscopic images.
      The latter enable the module to execute virtual back movement, e.g. in case of
      bleeding. Several other modules are offered. The aim of the study was the
      ergonomic analysis of different modules and their learning curves in cadaveric
      heads. The endoscope was navigated by the neurosurgeon while another person
      operated the computer. A total of 128 experiments were performed with two
      software versions. When the landmark tracking module was used, a real learning
      curve could be observed. By contrast, testing the measurement module did not
      produce a learning curve. A significant reduction of the time required by the
      three modules investigated could be observed with software version 2. The module
      for virtual back movement works best with a minimum time of 20 s for image
      storage. During machine-human interactions ergonomic software use is important,
      especially if operative procedures are performed.

PMID- 16455563
TI  - Cranio-orbital approach for complex aneurysmal surgery.
AB  - Certain aneurysms of the anterior circulation continue to offer a technical
      challenge for safe exposure and clipping. The purpose of this paper was to
      describe the cranio-orbital approach for surgical clipping of complex aneurysms
      and to evaluate prospectively the associated complications of this approach.
      Prospective audit of all patients undergoing cranio-orbital approach for aneurysm
      surgery from 1997 to 2004 by the senior author. Twenty-five patients, eight male
      and 17 female, median age of 52 years, range 28-73. All patients had a standard
      pterional approach supplemented by an orbital osteotomy. In the 7-year period 367
      patients underwent treatment for their aneurysms (169 clipped and 198 coiled). Of
      the 169 patients who were operated on, 29 had a skull base approach, of which 25
      were cranio-orbital. The aneurysm location was as follows: 16 middle cerebral
      artery (MCA), three carotid bifurcation, four anterior communicating artery
      (ACOMM), one ophthalmic and one basilar. There were no approach-related
      complications. The cranio-orbital craniotomy can be a useful adjunct in the
      surgical treatment of giant or complex aneurysms. It offers the following
      advantages over a standard pterional approach: reduces operative distance; allows
      easy splitting of the sylvian fissure; and provides a wide arc of exposure with
      multiple working corridors.

PMID- 16455564
TI  - In situ cranioplasty with methylmethacrylate and wire lattice.
AB  - Most techniques of cranioplasty are expensive and require advance preparation if
      a custom-moulded prosthesis is to be used. Technical problems with cranioplasties
      using synthetic materials include sinking, elevation and rotation, while those
      with hydroxyapatite or bone graft cranioplasties include resorption and harvest
      site disfigurement. We report our technique of in situ cranioplasty using
      methylmethacrylate and a wire lattice that is fast, inexpensive and avoids these
      technical problems.

PMID- 16455565
TI  - Solitary calvarial myofibroma presenting in adolescence.
AB  - Myofibroma is a benign fibrous tumour that may be found in the soft tissues,
      skeleton, and internal organs. It is a rare lesion but is the commonest fibrous
      tumour in infancy. Involvement of the skull has been reported in some 21 cases in
      the English-language literature. None of these, however, has arisen outside
      infancy. Here, we report a myofibroma arising from the temporal bone in a 17-year
      old girl.

PMID- 16455566
TI  - Primary hydatid disease of the spine: an unusual case.
AB  - Hydatid disease or hydatidosis caused by Echinococcus granulosus is the most
      widespread, serious human cestode infection in the world. Bone involvement is
      reported in 0.5-4% with spinal involvement reported in 50% of these cases. We
      report a case of this rare entity of an isolated primary hydatid cyst of the
      spine in a 15-year-old boy, who presented with progressive back pain for 8
      months, lower extremity weakness and urinary incontinence for 3 months.
      Neurological examination was suggestive of upper motor neuron type of paraperesis
      grade 1/5 with complete sensory loss below T4 level. MRI of the spine showed
      multiple cystic extradural lesions at the T4-5 level with involvement of the
      paraspinal muscles. The patient underwent a T4-5 laminectomy, and a total
      excision of the multiple epidural and paraspinal cysts. The diagnosis of hydatid
      disease was confirmed on histopathology. Albendazole was started postoperatively.
      At 6 months follow-up the boy had no neurological deficit, was playful, active
      and walking. Postoperative MRI at 6 months showed no recurrence of the lesion.
      Analysis of the other reported cases is discussed with relevance to our case.

PMID- 16455567
TI  - Papillary endothelial hyperplasia associated with repeated bleeding.
AB  - We report a case of intracranial papillary endothelial hyperplasia (PEH) with
      subsequent haemorrhage and the possible pathogenesis of bleeding. PEH is a slow
      growing tumour and for rapid enlargement the process of haemorrhage may be
      necessary.

PMID- 16455568
TI  - Primary intrasellar schwannoma: clinical, aetiopathological and surgical
      considerations.
AB  - Schwannomas originating within the sella turcica are extremely rare. We describe
      the clinical, radiological and intraoperative findings of a patient with an
      intrasellar and suprasellar schwannoma. Gross total tumour removal was performed
      by a trans-sphenoidal approach. Perivascular or ectopic Schwann cells, lateral
      nerve plexus within the cavernous sinus, as well as Schwann cells from small
      nerve twigs of the dura are some of the current histopathological hypotheses for
      the origin of these lesions.

PMID- 16455569
TI  - Depressed skull fracture overlying the superior sagittal sinus causing benign
      intracranial hypertension. Description of two cases and review of the literature.
AB  - The purpose of this report is to describe successful surgical treatment of benign
      intracranial hypertension (BIH) in two patients presenting with depressed skull
      fractures over the superior sagittal sinus (SSS). The first case involved a 22
      year-old patient who presented with depressed skull fracture overlying the
      posterior third of the SSS. Symptoms of BIH developed within 48 h. The second
      case involved a 33-year-old patient who presented with depressed skull fracture
      overlying the junction between the middle and posterior thirds of the SSS.
      Symptoms of BIH developed 1 month after. Although this patient presented with
      bilateral papilloedema, the less straightforward nature of his BIH symptoms
      prompted us to undertake further neuroradiological assessment by angiography with
      retrograde venous catheterization. A high-pressure gradient was found between
      venous flow upstream and downstream from the compressed zone. Both patients
      underwent surgical decompression in the lateral decubital position. Continuous
      monitoring of intracranial pressure was begun upon induction of general
      anaesthesia. High preoperative pressure declined immediately after elevation of
      the depressed zone. Bleeding was not a problem at any time during the procedure.
      Follow-up MRI and angio-MRI demonstrated total restoration of SSS patency. Benign
      intracranial hypertension is an uncommon complication of depressed skull
      fracture. Retrograde venous catheterization with pressure measurement can be a
      useful diagnostic adjunct. Surgical treatment is indicated in symptomatic
      patients. Based on the two cases reported, we now propose MRI venography in all
      patients presenting with symptoms of BIH and arteriography with retrograde venous
      catheterization when venous sinus stenosis exists.

PMID- 16455570
TI  - Phaeohyphomycosis: an unusual pituitary mass.
AB  - A 64-year-old Caucasian woman presented with left eye pain and a transient left
      oculomotor nerve palsy. Subsequent imaging revealed a mass involving the sphenoid
      sinus and sella with suprasellar extension. A trans-sphenoidal hypophysectomy was
      performed. Histopathology showed a fungal infection consistent with
      phaeohyphomycosis. Development of this lesion is probably attributed to allergic
      rhinitis and insulin-dependent diabetes mellitus. Intravenous amphotericin and
      itraconazole treatment resulted in full recovery and the patient remains well at
      6-month postoperative follow-up.

PMID- 16455571
TI  - Combined nasal and skull base pathology: adjacent nasal schwannoma and olfactory
      groove meningioma.
AB  - A 55-year-old woman presented with a longstanding history of headache and
      personality change. Preoperative imaging suggested an olfactory groove meningioma
      invading the posterior nasal space. Following surgical removal of the lesion
      histopathology confirmed the presence of both a nasal schwannoma and an olfactory
      groove meningioma. This dual pathology may represent a variation of
      neurofibromatosis type 2 (NF-2).

PMID- 16455572
TI  - Urinary bladder calculi complicating ventriculo-vesical shunt.
AB  - A rare case of vesical calculi complicating the procedure of ventriculo-vesical
      shunt is presented. In addition to highlighting technical difficulties in placing
      shunt catheters into the urinary system, the potential complications are
      discussed. We consider this route of cerebrospinal fluid(CSF) diversion less
      physiological compared with the peritoneal, pleural or the venous sites, and
      discourage use of the urinary bladder as the drainage site for the shunting of
      CSF.

PMID- 16455573
TI  - Rapid spontaneous resolution of a traumatic cervical epidural haematoma.

PMID- 16455577
TI  - Molecular mimicry in multiple sclerosis.
AB  - Two main etiological components are considered important in human autoimmune
      diseases including multiple sclerosis (MS), first the immunogenetic background
      and second environmental factors. Among the latter, infectious organisms are
      probably the most relevant, and epidemiological studies in MS firmly support that
      viral infections often precede disease exacerbations or the onset of MS.
      Infectious agents can contribute to disease development or phenotypic expression
      in different ways. Our focus will be directed on molecular mimicry, i.e.
      antigenic similarity between structural epitopes or peptide sequences from
      infectious organisms with those found in self proteins of the host. The
      intriguing concept of molecular mimicry has evolved substantially since its
      introduction over 20 years ago. We will summarize the most important developments
      and discuss puzzling questions, which remain open despite many claims that
      molecular mimicry is involved in the development of human autoimmune disease
      after infections or vaccinations.

PMID- 16455578
TI  - Multiple sclerosis and virus induced immune responses: autoimmunity can be primed
      by molecular mimicry and augmented by bystander activation.
AB  - Polymicrobial infections have been associated with plausible immune mediated
      diseases, including multiple sclerosis (MS). Virus infection can prime autoimmune
      T cells specific for central nervous system (CNS) antigens, if virus has
      molecular mimicry with CNS proteins. On the other hand, infection of irrelevant
      viruses will induce two types of cytokine responses. Infection with a virus such
      as lymphocytic choriomeningitis virus (LCMV), can induce interferon (IFN)
      alpha/beta production and suppress autoimmunity, while infection with a virus,
      such as murine cytomegalovirus (MCMV), can activate natural killer (NK), NKT and
      dendritic cells, resulting in interleukin (IL)-12 and IFN-gamma production. These
      cytokines can cause bystander activation of autoreactive T cells. We established
      an animal model, where mice infected with vaccinia virus encoding myelin protein
      can mount autoimmune responses. However, the mice develop clinical disease only
      after irrelevant immune activation either with complete Freund's adjuvant or MCMV
      infection. In this review, we propose that a combination of two mechanisms,
      molecular mimicry and bystander activation, induced by virus infection, can lead
      to CNS demyelinating diseases, including MS. Viral proteins having molecular
      mimicry with self-proteins in the CNS can prime genetically susceptible
      individuals. Once this priming has occurred, an immunologic challenge could
      result in disease through bystander activation by cytokines.

PMID- 16455579
TI  - Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of
      Sydenham's chorea.
AB  - Recent evidence suggests that the pathogenesis of Sydenham's chorea following
      group A streptococcal infection is due to antibodies which develop due to the
      infection and infiltrate the brain and basal ganglia. Antibodies present in acute
      chorea react with the surface of neuronal cells and signal the induction of
      calcium calmodulin dependent protein kinase II with elevation of tyrosine
      hydroxylase and subsequent dopamine release which may lead to the movement
      disorder. The antibodies present in disease recognize lysoganglioside and the
      group A streptococcal epitope, N-acetyl-glucosamine. Monoclonal antibodies (mAbs)
      from Sydenham's chorea demonstrated the mimicry between lysoganglioside and the
      group A streptococcal carbohydrate epitope. A group of antibodies present in
      pediatric autoimmune neuropsychiatric disorders (PANDAS) were similar but not
      identical to the antibodies observed in chorea.

PMID- 16455580
TI  - Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease.
AB  - Molecular mimicry is a hallmark of the pathogenesis of rheumatic fever where the
      streptococcal group A carbohydrate epitope, N-acetyl glucosamine, and the a
      helical coiled-coil streptococcal M protein structurally mimic cardiac myosin in
      the human disease, rheumatic carditis, and in animal models immunized with
      streptococcal M protein and cardiac myosin. Recent studies have unraveled the
      potential pathogenic mechanisms by which the immune response against the group A
      streptococcus attacks the rheumatic valve leading to chronic rheumatic heart
      disease. Both B- and T-cell responses are involved in the process, and evidence
      for the hypotheses of molecular mimicry and epitope spreading are reviewed.

PMID- 16455581
TI  - Induction of cardiac autoimmunity in Chagas heart disease: a case for molecular
      mimicry.
AB  - Up to 18 million of individuals are infected by the protozoan parasite
      Trypanosoma cruzi in Latin America, one third of whom will develop chronic Chagas
      disease cardiomyopathy (CCC) up to 30 years after infection. Cardiomyocyte
      destruction is associated with a T cell-rich inflammatory infiltrate and
      fibrosis. The presence of such lesions in the relative scarcity of parasites in
      the heart, suggested that CCC might be due, in part, to a postinfectious
      autoimmune process. Over the last two decades, a significant amount of reports of
      autoimmune and molecular mimicry phenomena have been described in CCC. The
      authors will review the evidence in support of an autoimmune basis for CCC
      pathogenesis in humans and experimental animals, with a special emphasis on
      molecular mimicry as a fundamental mechanism of autoimmunity.

PMID- 16455582
TI  - Autoimmunity in coxsackievirus B3 induced myocarditis.
AB  - Virus infections are implicated in several autoimmune diseases. Multiple
      mechanisms of autoimmunity induction have been proposed including antigenic
      mimicry, production of cryptic epitopes and infection acting as both adjuvant for
      self-antigens and the mechanism of releasing these cell antigens. Evidence for
      these mechanisms in coxsackievirus B3 induced myocarditis is discussed.

PMID- 16455583
TI  - Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE or lupus) is a complex disease with a
      multifactoral etiology, with genetic, hormonal, and environmental influences.
      Molecular mimicry as a result of viral infection may contribute to the
      development of lupus. The pattern of autoantibody development in lupus is
      consistent with initiation through molecular mimicry, as the initial
      autoantigenic epitopes that have been observed are limited and cross-reactive
      with viral proteins. Autoantibody specificity may then later diversify to other
      autoantigens through B-cell epitope spreading. Epstein-Barr virus (EBV) is an
      excellent candidate to be involved in molecular mimicry in lupus. EBV infection
      has been associated with lupus through serological and DNA studies. Infection
      with EBV results in the production of the viral protein Epstein-Barr virus
      nuclear antigen-1 (EBNA-1), antibodies against which cross-react with lupus
      associated autoantigens, including Ro, Sm B/B', and Sm D1, in lupus patients. The
      immune response against EBV, and EBNA-1 in particular, differs among lupus
      patients and healthy controls, with controls maintaining a limited humoral
      response and failing to produce long-standing cross-reactive antibodies. We
      hypothesize that the humoral immune response to EBNA-1 in susceptible individuals
      leads to the generation of cross-reactive antibodies. Through the process of
      epitope spreading, these cross-reactive antibodies target additional, non-cross
      reactive autoepitopes, spread to additional autoantigens, and become pathogenic,
      leading eventually to clinical lupus. This paper reviews some of the current
      literature supporting roles for EBV exposure and epitope spreading in SLE.

PMID- 16455584
TI  - Viruses and autoimmunity.
AB  - Viruses have been suspected as causes and contributors of human autoimmune
      diseases (AID), although direct evidence for the association is lacking. However,
      several animal models provide strong evidence that viruses can induce AIDs as
      well as act to accelerate and exacerbate lesions in situations where self
      tolerance is broken. Many models support the hypothesis by acting as molecular
      mimics that stimulate self-reactive lymphocytes. Mimicry alone is usually
      inadequate and with human AID, no compelling evidence supports a role for viruses
      that are acting as molecular mimics. Alternative mechanisms by which viruses
      participate in autoimmunity are non-specific, involving a mechanistically poorly
      understood process termed bystander activation or perhaps viral interference with
      regulatory cell control systems. This review briefly discusses examples where
      viruses are involved, taking the view point that molecular mimicry is over
      emphasized as a critical mechanism during AID pathogenesis.

PMID- 16455586
TI  - Effects of single intratracheal exposure to chlorhexidine gluconate on the rat
      lung.
AB  - Chlorhexidine gluconate (CHX) is an antiseptic that has been widely used for
      disinfection of cutaneous wound and gingivae. Recently, a patient who inhaled CHX
      solution died from acute respiratory distress syndrome (ARDS). Although it is
      highly possible that direct pulmonary damage might be the cause of ARDS, there is
      no preclinical information about the pulmonary toxicity of CHX. In the current
      study, the acute direct action of CHX to the lung was evaluated in rats. We
      successfully exposed the left but not the right lung either to CHX at
      concentrations of 1%, 0.1%, and 0.01% or to saline using a curved-tip
      administration tube. At the higher concentrations of CHX (0.1% and 1%), severe
      congestion to the alveoli and capillaries and perivascular and intra-alveolar
      hemorrhages were observed 1 day after exposure. Aniline blue-stained collagen
      fibers with an infiltration of inflammatory cells were present 7 days after
      exposure. The fibrotic changes and intra-alveolar inflammatory cells had
      decreased but were still observed sporadically 28 and 84 days after exposure.
      These detrimental effects were more severe at 1% than at 0.1% CHX. No remarkable
      effect was observed after exposures to 0.01% CHX and saline. We were able to
      evaluate the time-course changes in the pulmonary toxicity of CHX by exposures
      limited to the left lung. It is highly possible that CHX at a concentration of
      more than 0.1% might directly induce ARDS when aspirated and reaching to the
      alveoli.

PMID- 16455587
TI  - Hepatoprotective role of zinc in lead-treated, protein-deficient rats.
AB  - The current study was designed to evaluate the hepatoprotective role of zinc
      after lead (Pb) treatment of protein-deficient (PD) rats. The animals were
      subjected to seven different treatment groups: G-1 (normal control, 18% protein),
      G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of
      lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking
      water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn
      treated). Serum albumin levels and total serum protein contents were estimated to
      assess the severity of protein deficiency at the end of 8 weeks in all the
      treatment groups. Also, the study explored the role of zinc on antioxidative
      defense system enzymes in liver of protein-deficient rats subjected to lead
      toxicity treatment. Further, the study was extended to elucidate the levels of
      zinc and lead in liver tissue after different treatments of rats using positron
      induced X-ray emission technique (PIXE). The current study indicated a
      significant change in the levels of various antioxidative enzymes and serum
      albumin as well as total protein contents of protein-deficient rats subjected to
      lead treatment. A significant increase in the levels of malondialdehyde (MDA),
      catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead
      treatment of protein-deficient rats. On the contrary, levels of albumin, total
      protein content, superoxide dismutase (SOD), GSH, were found to be decreased.
      Interestingly, zinc supplementation has tended to normalize the altered levels of
      these enzymes to a significant extent. The levels of zinc in liver tissue was
      found to be decreased significantly in protein-deficient as well as lead-treated
      rats. However, hepatic zinc concentration was increased to a significant extent
      in protein-deficient rats supplemented with zinc when compared with protein
      deficient rats. Further, the presence of lead was also observed in livers of lead
      treated animals. In conclusion, the study revealed the antioxidative role of zinc
      in hepatotoxic conditions induced by subjecting the rats to protein-deficient
      diet and lead treatment.

PMID- 16455588
TI  - Radiation-induced in vitro phototoxic potential of some fluoroquinolones.
AB  - Photosensitizing drugs that can damage cellular biomolecules is a matter of
      concern. Lomefloxacin, norfloxacin, ofloxacin, and enoxacin (broad-spectrum
      antibiotics of fluoroquinolone group) are used for the treatment of Gram-positive
      and Gram-negative bacterial infections. Phototoxicity and possible mechanism of
      their action was assessed under the exposure of ambient levels of UV-A, UV-B, and
      sunlight at a concentration generally used in the treatment of various diseases.
      Singlet oxygen (1O2), superoxide anion radical (O2.-) generation, DNA damage, and
      lipid peroxidation in human blood were studied. All the fluoroquinolones tested
      in this study produced 1O2 and O2.- under exposure to UV-A, UV-B, and sunlight
      depending on the concentrations (0 to 60 microg/mL) of the drugs. Enoxacin showed
      a higher yield of 1O2 and O2.- than other drugs. These materials also degraded
      deoxyguanosine and induced lipid peroxidation in vitro under exposure to UV-A, UV
      B, and sunlight (depending on the dose of radiation). The formation of the
      reactive oxygen species (ROS) by the photoexcited drugs may be considered as a
      possible mechanism of their action.

PMID- 16455589
TI  - The in vitro permeability coefficient and short-term absorption rates for vinyl
      toluene using human cadaver skin mounted in a static diffusion cell model.
AB  - Vinyl toluene is one of several methylstyrene monomers that provide improved
      performance in resins for specialty paints, hydrocarbon resins for adhesives,
      specialty polymers, and unsaturated polyester resins. The purpose of this study
      was to determine a permeability coefficient (Kp) and short-term absorption rate
      for vinyl toluene using human cadaver skin mounted in an in vitro static
      diffusion cell model with an exposure area of 0.64 cm2. For the Kp determination,
      vinyl toluene was applied at a rate of 100 microL/cm2 to 6 skin replicates
      representing 4 human subjects. Serial receptor fluid samples were collected at 1,
      2, 4, 8, 12, 24, 36, and 48 h postapplication and analyzed for vinyl toluene by
      HPLC-UV. Based on the slope at steady-state (203.3 microg cm(-2) h(-1) +/- 120.0
      microg cm(-2) h(-1)) and the concentration of the applied dose of vinyl toluene,
      taken as its density (894,600 microg/cm3), the Kp was calculated to be 2.27 x 10(
      4) cm/h (+/-1.34 x 10(-4) cm/h). For the short-term absorption experiments, 12
      skin replicates representing 3 human subjects were employed. Following 10- and 60
      min exposures to a finite dose of vinyl toluene (10 microL/cm2), the respective
      short-term absorption rates were calculated to be 66.0 (+/-29.9) and 104.2 (+/
      63.0) microg cm(-2) h(-1). These data provide industrial hygienists and safety
      personnel values to estimate the amount of vinyl toluene that may be absorbed via
      the dermal exposure route, given a variety of exposure scenarios, and the time it
      takes (skin absorption time) to reach a body burden equal to the Occupational
      Safety and Health Administrative permissible exposure level (OSHA PEL) or ACGIH
      TLV.

PMID- 16455590
TI  - Sublethal effects of organophosphate diazinon on the brain of Cyprinus carpio.
AB  - Effects of diazinon, at different concentrations and exposure times, were
      investigated in freshwater fish, Cyprinus carpio, to elucidate the possible mode
      of action on lipid peroxidation together with the inhibitory effect of diazinon
      on acetylcholinesterase activity and changes in tissue protein levels.
      Cholinesterase inhibition is considered to be a specific biomarker of exposure to
      organophosphorus pesticides. Fish were exposed to 0.0036 microg/L, 0.018
      microg/L, and 0.036 microg/L (sublethal) concentrations of diazinon for 5, 15,
      and 30 days, and biochemical measurements were carried out
      spectrophotometrically. Brain was chosen as an indicator tissue because it is a
      target system for the organophosphorus action. More than 20% decline in
      acetylcholinesterase activity relative to mean activity of the controls was
      observed in the diazinon-exposed groups. Protein content decreased significantly
      after 15 days of exposure to 0.018 microg/L and 0.036 microg/L diazinon and after
      30 days of exposure to 0.036 microg/L. Malondialdehyde level declined markedly
      compared with the control levels. This study showed that prolonged exposures of
      C. carpio to diazinon had significant effects on brain acetylcholinesterase
      activity and that environmentally relevant concentrations of diazinon can
      significantly inhibit brain acetylcholinesterase activity. Altered protein
      content was probably due to the high energy demand under pesticide stress or
      inhibition of de novo enzyme synthesis. The decreased malondialdehyde content may
      reflect the possibility of better protection against oxidative stress.

PMID- 16455591
TI  - Evaluation of cytotoxic and mutagenic effects of Coriolus versicolor and Funalia
      trogii extracts on mammalian cells.
AB  - This study examined the in vitro cytotoxic activities of standardized aqueous
      bioactive extracts prepared from Coriolus versicolor and Funalia trogiiATCC
      200800 on HeLa and fibroblast cell lines using a MTT (3-[4,5-dimetiltiazol-2-]-2
      5-difeniltetrazolium bromide) cytotoxicity assay. F. trogii and C. versicolor
      extracts were cytotoxic to both cell lines. At 10 microL treatment level, F.
      trogii and C. versicolor extracts inhibited proliferation of HeLa cancer cells by
      71.5% and 45%, respectively, compared with controls. Toxicity was lower toward
      normal fibroblasts. In the latter case, treatment at 10 microL level with F.
      trogii and C. versicolor extracts reduced cell proliferation by 51.3% and 38.7%,
      respectively. In separate experiments, the mitotic index (MI) obtained with 3
      microL treatment level of unheated extracts of the two fungi was comparable to
      the MI value obtained by treatment with 4 microg/mL MMC (anticancer agent
      mitomycin-C). A significant induction of sister chromatid exchange (SCE) was
      observed in normal cultured lymphocytes treated with MMC (4 microg/mL). MMC
      treatment reduced replication index compared with treatment with unheated F.
      trogii extract and negative controls (p < 0.001). In contrast to MMC, F. trogii
      extracts did not affect the proliferation of human lymphocytes compared with
      controls (p > 0.05). Laccase and peroxidase enzyme activities in F. trogii
      extract were implicated in their inhibitory effect on cancer cells. F. trogii
      extract was concluded to have antitumor activity.

PMID- 16455592
TI  - The frequency of sister chromatid exchanges in cultured human peripheral blood
      lymphocyte treated with metronidazole in vitro.
AB  - 5-Nitroimidazoles are a group of antiprotozoal and antibacterial agents. Thanks
      to their antimicrobial activity, these chemotherapeutic agents inhibit the growth
      of both anaerobic bacteria and certain anaerobic protozoa. One of the useful
      drugs used in the treatment of infections caused by Trichomonas vaginalis,
      Entamoeba histolytica, and Giardia lamblia is metronidazole (MTZ). The
      mutagenicity of metronidazole [1-(hydroxyethyl)-2-methyl-5-nitroimidazole] has
      been previously shown in different prokaryotic systems but not in eukaryotic
      systems. The objective of this study is to determine the mutagenic and cytotoxic
      effects of MTZ at plasma concentration and higher in vitro. In this study, we
      evaluated the mutagenicity and cytotoxicity of MTZ in cultured human peripheral
      blood lymphocytes. Doses were selected according to plasma concentration of drug.
      End points analyzed included mitotic index (MI), replication index (RI), and
      sister chromatid exchange (SCE). An analysis of variance test (ANOVA) was
      performed to evaluate the results. A significant decrease (p < 0.001) in MI and
      RI as well as an increase in SCE frequency (p < 0.001) was observed compared with
      control cultures. Our results indicate the genotoxic and cytotoxic effect of MTZ
      in cultured human peripheral blood lymphocytes at plasma concentrations slightly
      higher than encountered therapeutically.

PMID- 16455593
TI  - Hematological and clinical chemistry changes induced by subchronic dosing of a
      novel phosphorothionate (RPR-V) in Wistar male and female rats.
AB  - A novel phosphorothionate [2-butenoic acid-3-(diethoxy phosphinothioyl)-ethyl
      ester; RPR-V] synthesized at Indian Institute of Chemical Technology (Hyderabad,
      India) was studied using subchronic doses of 0.033 (low), 0.066 (medium), and
      0.099 (high) mg kg(- 1) in male and female rats daily for 90 days. Continuous
      treatment with RPR-V caused significant (p < 0.05) decreases in body-weight gain,
      feed intake, hemoglobin (Hb), hematocrit (Hct), and total erythrocyte count
      (TEC), whereas total leukocyte count (TLC), mean corpuscular volume (MCV), mean
      corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration
      (MCHC) were increased. Similarly, RPR-V caused significant elevation in serum
      clinical chemistry parameters calcium, phosphorus, creatinine, and chloride
      contents, whereas protein and glucose levels were depressed in both male and
      female treated rats after 45 and 90 days of treatment. These alterations were
      significant when compared with two-way ANOVA showing that these changes were dose
      and time-dependent. The effects of low dose were generally not statistically
      significant, whereas medium and high doses caused significant effects. The
      changes in male rats were not significant when compared with female rats showing
      no sexual dimorphism by this compound. Recovery was observed after 28 days post
      treatment (withdrawal study), indicating that the compound entered into the
      system was eliminated from the body, and the blood parameters were improved.
      Hematological and clinical chemistry parameters can be detected rapidly and hence
      can be used for prediction and diagnosis of pesticide toxicity. Alterations in
      these parameters show toxic stress in the treated animals especially on blood and
      blood-forming organs.

PMID- 16455594
TI  - Lead-induced genotoxicity in lymphocytes from peripheral blood samples of humans:
      in vitro studies.
AB  - Lead is a known toxicant that has been implicated in encephalopathy in children
      and may affect the gastrointestinal and hematopoietic and other systems in
      adults. In fact, lead has been shown to compete with calcium for entry into the
      synaptosome and induce toxic effects. The aim of the current study was to
      evaluate the cytotoxic and genotoxic effects of lead by using lymphocytes from
      human peripheral blood in vitro. The LC50 for lead nitrate as determined by
      Trypan blue dye exclusion technique was found to be 3.14 mM. Chromosomal
      aberration frequency at sublethal doses (1/10 of LC50) as determined by examining
      the metaphase chromosomes (karyotyping) did not show significant aberrations
      except for some aneuploidy and about 2-4% gaps, breaks (3-4%), and about 5%
      satellite associations. However, significant DNA damage was determined by SCGE
      (Comet assay). The comet tail length proportionately increased with increasing
      lead nitrate concentration. Thus, Pb can induce single-strand DNA breaks,
      possibly by competing with metal binding sites.

PMID- 16455595
TI  - Retinal toxicity of intraocular vancomycin and ceftazidime in vitrectomized
      rabbit eyes.
AB  - The purpose of this study was to evaluate the retinal toxicity of vancomycin and
      ceftazidime combined into an infusion solution that was intraoculary given after
      or during vitrectomy. Forty albino rabbits were divided into 4 groups of 10 each.
      Vitrectomized right eyes of groups 1, 2, and 3 were given recommended doses of
      vancomycin and ceftazidime alone or combined, while right eyes in the fourth
      group were vitrectomized using an infusion solution to which was added
      ceftazidime and vancomycin combination. Toxicity was tested with
      electroretinography (ERG) and light microscopy. ERG and light microscopy did not
      show any toxicity signs associated with vancomycin or ceftazidime alone or with
      combined therapy. Vancomycin and/or ceftazidime can reliably and effectively be
      used combined in an infusion solution at recommended doses after and during
      vitrectomy. This treatment modality does not have any toxic effects to retinal
      structures and is an alternative method to separate injections of the two
      antimicrobial agents.

PMID- 16455599
TI  - Preclinical anticancer activity of DNA-based cleavage molecules.
AB  - Deoxyribozymes (DNAzymes) are DNA residue-based molecules capable of specific
      cleavage of complementary mRNA. As such, they are more stable counterparts for
      the earlier discovered ribozymes. A handful of studies have shown the potential
      of DNAzymes against cancer both in cell culture and importantly in vivo models.
      This relatively new molecular entity may progress to clinical trials provided
      that more extensive testing is carried out at the preclinical stage. While a
      significant amount of work has gone into chemically stabilizing the molecule,
      delivery is one area that needs particular attention.

PMID- 16455600
TI  - Multivariate methods in the development of a new tablet formulation: excipient
      mixtures and principal properties.
AB  - A tablet formulation for direct compression has previously been studied using
      multivariate design. An optimization study of one of the most important tablet
      properties, disintegration time, revealed that excipients with Principal
      Properties (PP's) that were predicted as suitable by the model were not
      represented within the studied material. The feasibility of using mixtures of
      excipients in the multivariate approach to tablet formulation to solve this
      problem has been investigated in the present study. By mixing different
      excipients of the same excipient class, it should be possible to obtain mixtures
      with the predicted PP's, which in turn should give a formulation with the desired
      properties. In order to investigate the utility of this approach, separate
      mixture designs were applied to both binders and fillers (diluents). As reported
      here, the Partial Least Squares Projections to Latent Structures (PLS) model
      developed in the previously published screening study has been validated in the
      sense that the interesting region of the PP space identified in it has been shown
      to contain excipients, pure or mixed, that give the formulation suitable
      properties. Formulations with suitable properties were found with the mixture
      experiments. The local models also offer several alternatives for the composition
      of the formulation that yield the desired disintegration time.

PMID- 16455601
TI  - Temperature stability and bioadhesive properties of delta9-tetrahydrocannabinol
      incorporated hydroxypropylcellulose polymer matrix systems.
AB  - The purpose of this study was to determine and compare the bioadhesive profiles
      of hydroxypropylcellulose (HPC) polymer matrices as a function of delta9
      tetrahydrocannabinol (THC) content. In addition, the effect of processing
      temperature on the stability of THC and its extent of degradation to cannabinol
      (CBN) was investigated. A hot-melt cast molding method was used to prepare HPC
      polymer matrix systems incorporated with THC at 0, 4, 8, and 16 percent.
      Bioadhesive measurements including peak adhesive force, area under the curve, and
      elongation at adhesive failure were recorded utilizing the TA.XT2i Texture
      Analyzer. Data obtained from these tests at various contact time intervals
      suggested that the incorporation of THC led to an increase in the bioadhesive
      strength of the HPC polymer matrices. To determine the stability of THC and the
      resulting CBN content in the matrices, three different processing temperatures
      were utilized (120, 160, and 200 degrees C). Post-production High Performance
      Liquid Chromotography (HPLC) analysis revealed that the processed systems
      contained at least 94% of THC and the relative percent formation of CBN was 0.5%
      at 120 degrees C and 0.4% at 160 degrees C compared to 1.6% at 200 degrees C.
      These findings indicate that the cannabinoid may be a plausible candidate for
      incorporation into systems utilizing hot-melt extrusion techniques for the
      development of an effective mucoadhesive transmucosal matrix system for delivery
      of THC.

PMID- 16455602
TI  - Influence of enzymes and surfactants on the disintegration behavior of cross
      linked hard gelatin capsules during dissolution.
AB  - Gelatin exhibits cross-linking upon storage at stress conditions. Capsules stored
      at these conditions fail to show appropriate in vitro dissolution. The aim of
      this study is to show the effect of surfactants in the medium on the
      disintegration of the gelatin capsule. This is demonstrated in the presence and
      absence of the enzymes pancreatin and pepsin, the function of which is to improve
      the dissolution. Sodium lauryl sulfate (SLS) and Tween 80 are tested as
      surfactants. When SLS is used in the medium, dissolution is significantly
      hampered due to the formation of a less soluble precipitate of gelatin. Compared
      to SLS, Tween 80 shows far better disintegration and solubility results in
      dissolution media with neutral or low pH. Therefore, it is concluded in this
      study that Tween 80 is preferred when a surfactant is necessary to comply with
      sink condition requirements.

PMID- 16455603
TI  - Preparation of theophylline-hydroxypropylmethylcellulose matrices using
      supercritical antisolvent precipitation: a preliminary study.
AB  - Several controlled release systems of drugs have been elaborated using a
      supercritical fluid process. Indeed, recent techniques using a supercritical
      fluid as a solvent or as an antisolvent are considered to be useful alternatives
      to produce fine powders. In this preliminary study, the effect of Supercritical
      Anti Solvent process (SAS) on the release of theophylline from matrices
      manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two
      grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare
      a sustained delivery system for theophylline which was used as a model drug. The
      characterization of the drug before and after SAS treatment, and the
      coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and
      Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline,
      theophylline-coprecipitates, and matricial tablets prepared with coprecipitates
      were determined. The physical characterizations revealed a substantial
      correspondence of the drug solid state before and after supercritical fluid
      treatment while drug-polymer interactions in the SAS-coprecipitates were
      attested. The dissolution studies of the matrices prepared compressing the
      coprecipitated systems showed that the matrices based on HPMC K100 were able to
      promote a sustained release of the drug. Further, this advantageous dissolution
      performance was found to be substantially independent of the pH of the medium.
      The comparison with the matrices prepared with untreated substances demonstrated
      that matrices obtained with SAS technique can provide a slower theophylline
      release rate. A new mathematical model describing the in vitro dissolution
      kinetics was proposed and successfully tested on these systems.

PMID- 16455604
TI  - Design and evaluation in vitro of controlled release mucoadhesive tablets
      containing chlorhexidine.
AB  - This investigation deals with the development of buccal tablets containing
      chlorhexidine (CHX), a bis-bis-guanide with antimicrobial and antiseptic effects
      in the oral cavity, and able to adhere to the buccal mucosa to give local
      controlled release of drug. A mucoadhesive formulation was designed to swell and
      form a gel adhering to the mucosa and controlling the drug release into the oral
      cavity. Some batches of tablets were developed by direct compression, containing
      different amounts of hydroxypropylmethylcellulose (HPMC) and carbomer; changing
      the amount ratio of these excipients in formulations, it is possible easily
      modulate the mucoadhesive effect and release of drug. The in vitro tests were
      performed using the USP 26/NF paddle apparatus, a specifically developed
      apparatus, and a modified Franz diffusion cells apparatus. This last method
      allows a simultaneous study of drug release rate from the tablets and drug
      permeation through the buccal mucosa. Similar tests have also been carried out on
      a commercial product, Corsodyl gel, in order to compare the drug release control
      of gel with respect to that of the mucoadhesive tablet, as a formulation for
      buccal delivery of CHX. While the commercial formulation does not appear to
      control the release, the formulation containing 15% w/w methocel behaves the
      best, ensuring the most rapid and complete release of the drug, together with a
      negligible absorption of the active agent as required for a local antiseptic
      action in the oral cavity.

PMID- 16455605
TI  - Development of a thermogelling ophthalmic formulation of cysteine.
AB  - Preliminary studies carried out with cysteine 2% solution showed that pH adjusted
      to isoelectrical pH (i.e., 4.9) led to enhance stability during autoclaving and
      ensured no significant degradation during at least 14 days if stored at 2-8
      degrees C protected from light. Optimized formulations combined either
      cysteine(2%)/Poloxamer407(16.5%) or
      cysteine(2%)/Poloxamer407(20%)/Poloxamer188(5%) and were characterized by an
      adequate temperature of gelification (TG) (25.9 degrees C and 26.9 degrees C,
      respectively), an important gel strength (5.1daN and 5.3daN, respectively) and a
      drastic increase in the apparent viscosity between 24 degrees C and 32 degrees C
      (multiplication factor of 78 and 77-fold, respectively). Cysteine addition
      produced only slight but significant decrease in temperature of gelification and
      increase in gel strength.

PMID- 16455606
TI  - Preparation of hydrophobic drugs cyclodextrin complex by lyophilization monophase
      solution.
AB  - A novel method was evaluated for preparation of hydrophobic drugs cyclodextrin
      (CD) complex in this study. To obtain sterilized drug-CD complex lyophilized
      powder for injection or other purpose, the CD solution in water and the
      hydrophobic drug in tertiary butyl alcohol (TBA) were mixed in a suitable volume
      ratio, filtered through 0.22 microm millpores, and subsequently freeze-dried. A
      high drug concentration was obtained in the co-solvent due to the good solvency
      of TBA, which is miscible with water in any proportion, for hydrophobic drugs.
      Moreover, TBA could be removed rapidly and completely by freeze-drying because of
      its high vapor pressure and high melting point. The chemical stability of some
      labile active compounds was also improved in TBA-water co-solvent. Based on the
      data from differential scanning calormetry (DSC) and X-ray diffractometry (XRD),
      drug was amorphous in freeze-dried complex. The fourier transform infrared
      spectra indicated drug-CD interaction was present in drug-CD complex. An enhanced
      dissolution rate was also obtained in drug-CD complex. These results proved drug
      CD complex had been formed after this technique. Thus, this report provided a
      simple, efficient, and economic technique for preparation of hydrophobic drugs CD
      complex, which may be useful practically in modifying hydrophobic drugs
      physicochemical properties and improving their absorption and pharmacodynamics.

PMID- 16455607
TI  - In vitro and in vivo release of naltrexone from biodegradable depot systems.
AB  - The aim of this study was to prepare poly(d, l-lactide) (PLA) microspheres
      containing naltrexone (NTX) by a solvent evaporation method, and to evaluate both
      in vitro and in vivo release characteristics and histopathological findings of
      tissue surrounding an implant formulation in rats. This method enabled the
      preparation of microspheres of regular shape and relatively narrow particle size
      distribution. The in vitro release profiles of NTX from PLA microspheres showed
      the release of NTX did not follow zero-order kinetics. An initial burst release
      was observed, subsequently followed by a nearly constant rate of 0.4% per day
      after ten days. The cumulative amount of NTX released at the end of 60 days was
      80%. Compressed microspheres showed near zero-order sustained release of NTX for
      360 days. The plasma NTX levels in rats showed that for compressed microspheres
      NTX concentrations were constant and exceeded 2 ng/mL for 28 days. Throughout the
      28 days of study, the implantations cause a minor inflammatory response, which
      can be regarded as a normal defence mechanism. The sustained release performance
      of NTX from the biodegradable depot systems may provide a reliable, convenient,
      and safe mechanism for the administration of NTX for the long-term treatment of
      opioid dependence.

PMID- 16455608
TI  - Directly compressed mini matrix tablets containing ibuprofen: preparation and
      evaluation of sustained release.
AB  - Directly compressed mini tablets were produced containing either
      hydroxypropylmethylcellulose (HPMC) or ethylcellulose (EC) as release controlling
      agent. The dynamics of water uptake and erosion degree of polymer were
      investigated. By changing the polymer concentration, the ibuprofen release was
      modified. In identical quantities, EC produced a greater sustaining release
      effect than HPMC. Different grades of viscosity of HPMC did not modify ibuprofen
      release. For EC formulations, the contribution of diffusion was predominant in
      the ibuprofen release process. For HPMC preparations, the drug release approached
      zero-order during a period of 8 h. For comparative purposes, tablets with 10 mm
      diameter were produced.

PMID- 16455609
TI  - Influence of sucrose esters on the in vivo percutaneous penetration of octyl
      methoxycinnamate formulated in nanocapsules, nanoemulsion, and emulsion.
AB  - The influence of sucrose laureate and sucrose oleate on the in vivo percutaneous
      penetration of octyl methoxycinnamate (OMC) formulated in i) colloidal
      suspensions (nano-emulsions and nanocapsules), and ii) conventional o/w emulsions
      was evaluated. The results showed that nano-emulsions formulated with sucrose
      laureate exhibited the highest penetration in the stratum corneum compared to the
      other formulations. A two-fold increase in OMC skin deposition was observed with
      the nano-emulsion containing sucrose laureate when compared to the control. The
      data obtained suggest that the total amount of OMC detected in the stratum
      corneum and the penetration depth are strongly dependent upon the formulation's
      nature, the particle size, and the type of enhancer.

PMID- 16455610
TI  - Enhancing the bioavailability of cyclosporine a using solid dispersion containing
      polyoxyethylene (40) stearate.
AB  - Solid dispersion containing polyoxyethylene (40) stearate and cyclosporine A was
      prepared by solvent-melt method and characterized using differential scanning
      calorimetry, powder X-ray diffraction, and Infrared Fourier Transform
      Spectroscopy (FTIR). Dissolution of the drug from solid dispersion was
      dramatically enhanced compared to that from the drug powder alone and physical
      mixture. In vivo oral bioavailability of cyclosporine A from the solid dispersion
      in Wistar rats was comparable to that from a commercial product, Sandimmun Neoral
      (P>0.05). The formulation is stable up to six months under 30 degrees C/RH60% and
      one year at 25 degrees C/RH 60% when packed in aluminum-polyethylene laminated
      bags.

PMID- 16455611
TI  - Influence of particle size on the distributions of liposomes to atherosclerotic
      lesions in mice.
AB  - In order to confirm the efficacy of liposomes as a drug carrier for
      atherosclerotic therapy, the influence of particle size on the distribution of
      liposomes to atherosclerotic lesions in mice was investigated. In brief,
      liposomes of three different particle sizes (500, 200, and 70 nm) were prepared,
      and the uptake of liposomes by the macrophages and foam cells in vitro and the
      biodistributions of liposomes administered intravenously to atherogenic mice in
      vivo were examined. The uptake by the macrophages and foam cells increased with
      the increase in particle size. Although the elimination rate from the blood
      circulation and the hepatic and splenic distribution increased with the increase
      in particle size in atherogenic mice, the aortic distribution was independent of
      the particle size. The aortic distribution of 200 nm liposomes was the highest in
      comparison with the other sizes. Surprisingly, the aortic distribution of
      liposomes in vivo did not correspond with the uptake by macrophages and foam
      cells in vitro. These results suggest that there is an optimal size for the
      distribution of liposomes to atherosclerotic lesions.

PMID- 16455614
TI  - Effects of di(2-ethylhexyl) phthalate, a widely used peroxisome proliferator and
      plasticizer, on cell growth in the human keratinocyte cell line NCTC 2544.
AB  - Phthalate esters are a widely used class of water-insoluble organic chemicals.
      The adverse effects of di(2-ethylhexyl) phthalate (DEHP) were chiefly studied in
      animals, while their potential toxicity to humans has not been properly
      evaluated. It was hypothesized that the effect of DEHP on human cells depends on
      the concentration, and this study examined the effects of different
      concentrations of DEHP on cell growth in cultured human keratinocytes NCTC 2544,
      together with the possible involvement of peroxisome proliferator-activated
      receptors (PPARs) in mediating the effects. After exposure to DEHP, the number of
      NCTC 2544 cells in the monolayer decreased in a concentration-dependent and time
      dependent manner, whereas the cells that were detached from the monolayer
      increased, and died via necrosis. The decrease of cell growth was confirmed by
      the inhibition of pErk1, pErk2, and changes in the c-myc protein content. With
      regard to PPARs, the PPARbeta protein content increased, whereas PPARalpha
      decreased. To demonstrate the involvement of PPARbeta in inhibiting cell growth,
      the use of an antisense oligonucleotide against this receptor revealed the
      prevention of DEHP-induced cell growth inhibition. In addition, the treatment of
      keratinocytes with a specific ligand of PPARbeta (L165041) showed a concentration
      dependent inhibition of cell growth, as with DEHP. In conclusion, the effect of
      DEHP on human keratinocytes is concentration dependent, and this effect is
      mediated via PPARs.

PMID- 16455615
TI  - Fatty liver and hepatic function for residents with markedly high serum PCDD/Fs
      levels in Taiwan.
AB  - This study was designed to examine the associations between serum polychtorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) levels and adverse hepatic-related
      health outcomes. Residents living in the vicinity of a closed pentachlorophenol
      (PCP) manufacturing factory (exposure area) and other areas nearby (control area)
      were identified from prior investigation of serum PCDD/Fs measurements. A total
      of 85 subjects were recruited for the study, 52 from exposure area and 33 from
      control, respectively. Average level of serum PCDD/Fs was 80.1 6 50.9 pg WHO
      TEQ/g lipid for those residing in exposure area, and 25.5 6 18.2 in control area.
      Statistically higher odds ratio (ORs) for fatty liver and gamma
      glutamyltransferase (GGT) activity was found in subjects with higher serum
      PCDD/Fs levels and high body mass index (BMI) as compared to those with lower
      PCDD/Fs levels and less BMI. Data suggest that dioxin exposure and high lipid
      content affect the prevalence of fatty liver in exposed subjects. Future study
      should be directed to prevent continuous exposure to environmental PCDD/Fs from
      the defunct PCP factory, and to characterize prospectively, with a larger study
      sample size, the potential long-term consequences on hepatic function associated
      with contaminant exposure.

PMID- 16455616
TI  - The effects of ellagic acid and vitamin E succinate on antioxidant enzymes
      activities and glutathione levels in different brain regions of rats after
      subchronic exposure to TCDD.
AB  - Ellagic acid (EA) and vitamin E succinate (VES) were previously shown to protect
      against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced reactive oxygen
      species (ROS) overproduction in certain brain regions of rats after subchronic
      exposure. The current study was designed to assess the modulation of antioxidant
      enzyme activities and glutathione (GSH) levels as protective measures for VES and
      EA against TCDD-induced ROS overproduction in four regions of rat brain. TCDD was
      administered to groups of rats at a daily dose of 46 ng/kg for 90 d. EA and VES
      were administered to some other groups of rats either alone or simultaneously
      with TCDD, every other day for 90 d. At the end of the treatment period, animals
      were sacrificed and brain regions were dissected, including cerebral cortex (Cc),
      hippocampus (H), cerebellum (C), and brainstem (Bs), for assay of superoxide
      dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities,
      as well as GSH levels. While treatment of rats with VES alone or in combination
      with TCDD resulted in significant increases in SOD and CAT activities in
      different brain regions, treatment with EA resulted in a significant rise in
      total GSH levels and GSH-Px activity in those regions. Results may suggest
      antioxidant modulation by VES and EA as a mechanism for the previously observed
      protection by these compounds against TCDD-induced ROS overproduction in brain.
      Data also indicate there are two different pathways in the protection provided by
      the two antioxidants.

PMID- 16455617
TI  - Productivity of tree swallows (Tachycineta bicolor) exposed to PCBs at the
      Kalamazoo River superfund site.
AB  - A 123-km stretch of the Kalamazoo River in Michigan, was designated a Superfund
      site in 1990 due to historical releases of effluent containing polychlorinated
      biphenyl (PCB)-contaminated paper waste. Risk to bird species in the river
      ecosystem was evaluated using the tree swallow (Tachycineta bicolor) as a monitor
      for possible effects due to PCB exposure at two nesting locations, one in the
      Superfund site and one in an upstream reference location that is less
      contaminated with PCBs. In 2 of the 3 years of the study, clutch size at the
      contaminated location was 3.7 +/- 1.4 and 4.8 +/- 0.73 eggs per nest (mean +/-
      SD), which was significantly less than the clutch size at the reference location
      (5.0 +/- 1.1 and 5.3 +/- 1.1 eggs per nest). However, there were no statistically
      significant differences in fledging success, predicted brood size, predicted
      number of fledglings, or growth of nestlings between the Kalamazoo River
      Superfund site and an upstream reference location with lesser concentrations of
      PCBs in the sediments and riparian soils. Productivity and hatching success
      comparisons between these same sites were also not significantly different;
      however, the power of these conclusions was less (p < .10). The reduction in
      clutch size at the co-contaminated location could not be attributed to PCBs due
      to a number of confounding factors, including Co-cocontaminants, habitat
      structure, and food availability. Other reproductive parameters were not
      significantly impaired, and the size of the newly established colony at the
      Kalamazoo River Superfund site continued to grow over the period of the study.
      These site-specific observations, combined with multiple lines of evidence
      approach that considered results reported for the effects of both total PCBs and
      2,3,7,8 tetrachlorodibenzo-p-dioxin equivalents (TEQ) on tree swallows at other
      locations, suggest that there were no significant population-level effects of
      PCBs on tree swallows at the Kalamazoo River Superfund site.

PMID- 16455618
TI  - Transcription factor ETS1 is critical for human uterine decidualization.
AB  - The aim of this study was to examine whether the transcription factor ETS1 plays
      a critical role in the regulation of human decidualization. Decidual fibroblast
      cells were decidualized in vitro by treatment with medroxyprogesterone, estradiol
      (E(2)) and dibutyryl cyclic AMP or prostaglandin E(2) in the absence or presence
      of an ETS1 antisense oligonucleotide (oligo) that blocks the translation of ETS1
      mRNA. Control experiments were performed using a control oligo that did not
      affect ETS1 expression and the induction of specific marker genes for
      decidualization. The ETS1 antisense oligo markedly inhibited ETS1 protein
      expression and significantly inhibited downstream targets of ETS1 action. On day
      6 of culture, the decidualized fibroblast cells that had been exposed to the ETS1
      antisense oligo contained 40-90% less mRNAs for prolactin, insulin growth factor
      binding protein 1 (IGFBP-1) and other decidualization-specific markers (laminin,
      tissue inhibitor of metalloproteinase-3 [TIMP3], endometrial bleeding associated
      factor [EBAF] and decorin) than those of control cells that had not been exposed
      to the ETS1 antisense oligo. GAPDH mRNA levels, which do not change during
      decidualization, were unaffected by either the ETS1 antisense or the control
      oligo. The cells decidualized in the presence of the ETS1 antisense oligo also
      released significantly less prolactin, EBAF and IGFBP-1 protein, determined by
      western blot analyses, than the control cells. Taken together, these findings
      strongly suggest that ETS1 plays a critical role in the induction of human
      decidualization.

PMID- 16455619
TI  - Anti-inflammatory and relaxatory effects of prostaglandin E2 in myometrial smooth
      muscle.
AB  - The onset of human labour is complex and involves multiple mediators,
      prostaglandins, cytokines and chemokines. However, whilst prostaglandins are
      routinely used for labour induction and inhibitors of prostaglandin synthesis are
      used to prevent pre-term labour, these practices are not invariably successful,
      and the rationale for their use is equivocal. As COX-2 and prostaglandin E(2)
      (PGE(2)) production is increased towards term, we have investigated the effect of
      PGE(2) and other cAMP-elevating agents on events associated with labour
      induction. Time-dependent increases in granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and interleukin-8 (IL-8) release were observed following
      treatment of primary human myometrial smooth muscle (HMSM) cells with IL-1beta,
      via mechanisms that required de novo transcription and translation. Prior
      treatment with PGE(2) (1 microM) produced 86 and 80% decreases in GM-CSF and IL-8
      release, respectively. Similarly, the cAMP analogue, 8-bromo-cAMP (8Br-cAMP) and
      the phosphodiesterase-4 (PDE(4)) inhibitor, rolipram, also repressed GM-CSF and
      IL-8 release. In addition, PGE(2), 8Br-cAMP, rolipram and salbutamol all had a
      dose-dependent inhibitory effect on spontaneous myometrial contractions in vitro.
      In this study, PGE(2) reduced the release of factors associated with cervical
      ripening and attenuated force development in myometrial smooth muscle, raising
      the possibility that in myometrium, PGE(2) may act to down-regulate some of the
      processes that contribute to the onset of human labour and may be beneficial in
      helping to maintain pregnancy towards term.

PMID- 16455620
TI  - Association between a functional dopamine D4 receptor promoter region
      polymorphism (-C521T) and pre-eclampsia: a family-based study.
AB  - Although many candidate genes have been studied in pre-eclampsia (PE), the
      important class of catecholamine receptors that contribute to sympathetic tone
      and blood pressure regulation has yet to be investigated. We therefore examined
      the dopamine D4 receptor (DRD4) gene. We performed a prospective family-based
      study in 50 families (patient and both her parents) who were genotyped for three
      DRD4 promoter regions. These single-nucleotide polymorphisms (SNPs) were tested
      for association using family-based association test (FBAT) that also included two
      quantitative measures, aspartate aminotransferase [serum glutamic oxalacetic
      transaminase (SGOT)] and systolic blood pressure. SNPs were assayed using a
      commercially available SNAPSHOT kit and PCR products were analysed in an ABI 310
      DNA analyser. A significant association (preferential transmission of the T
      allele from a heterozygous parent to affected mother) was observed between the 
      C521T SNP and PE (P = 0.019). Significant association was also observed between
      the -521T allele and two-dimensional measures of PE : GOT (P = 0.039) and
      systolic blood pressure (P = 0.036). The DRD4 promoter region -C521T SNP that
      reduces transcriptional efficiency of this gene is suggested to contribute to
      developing PE. Additionally, DRD4 -521 TT homozygosity may be a marker for severe
      PE.

PMID- 16455621
TI  - Polymorphisms in the promoter regions of the matrix metalloproteinases-7, -9 and
      the risk of endometriosis and adenomyosis in China.
AB  - Matrix metalloproteinases (MMPs) may contribute to the development of
      endometriosis. The aim of this study was to assess the effects of the
      polymorphisms in the promoters of MMP-7 (181A/G) and MMP-9 (1562C/T) on the risk
      of occurrence of endometriosis and adenomyosis. We genotyped 219 patients (143
      women with endometriosis, 76 women with adenomyosis) and 160 control women in
      North China. There was a significant difference in frequency of the MMP-7
      genotype between endometriosis and controls (P = 0.01) and also between
      adenomyosis and controls (P = 0.01). The frequency of the G allele in two groups
      of patients (7.3 and 7.9%) was significantly higher than in the controls (2.8%)
      (P = 0.01 and 0.01, respectively). Compared to the A/A genotype, the genotype
      with the -181G allele showed a significantly increased susceptibility to both
      diseases, with adjusted odds ratio of 2.62 [95% confidence interval (CI) = 1.17
      5.87] for endometriosis and 3.14 (95% CI = 1.26-7.81) for adenomyosis. However,
      the overall genotype and allelotype distribution of the MMP-9 in the two case
      groups were not different from that of controls. We conclude that MMP-7-181A/G
      polymorphism has a potential to be a susceptibility factor for endometriosis and
      adenomyosis while MMP-9-1562C/T polymorphism may not provide a useful marker to
      predict susceptibility to endometriosis and adenomyosis, at least in women from
      North China.

PMID- 16455622
TI  - Sentinel lymph node biopsy in melanoma.

PMID- 16455623
TI  - Radioimmunotherapy of solid tumors: the promise of pretargeting strategies using
      bispecific antibodies and radiolabeled haptens.

PMID- 16455624
TI  - 18F-CPFPX PET: on the generation of parametric images and the effect of scan
      duration.
AB  - 8-cyclopentyl-3-(3-18F-fluoropropyl)-1-propylxanthine (18F-CPFPX) is a novel PET
      ligand for in vivo quantification of cerebral A1 adenosine receptors. The present
      study investigated the applicability of voxelwise graphical analysis to the
      generation of parametric images of the total volume of distribution (DVt) of 18F
      CPFPX as a prerequisite for voxel-by-voxel statistical analysis. The benefit of
      spatial smoothing for reduction of noise-dependent negative bias in graphical
      analysis was examined. Additionally, the effect of scan duration on the accuracy
      of analyses based on volumes of interest (VOIs) and individual voxels was
      explored. METHODS: Ten healthy male volunteers underwent bolus-injection 18F
      CPFPX PET (90 min). The data were analyzed using a 2-tissue-compartment model and
      graphical analysis. Voxelwise graphical analysis was performed with and without
      preceding spatial gaussian smoothing. RESULTS: Voxelwise graphical analysis
      yielded high-quality parametric images. However, voxelwise graphical analysis
      suffered from a negative bias (mean bias in cortical regions, -9.6% to -7.5%),
      which could be attenuated considerably by spatial smoothing (using a kernel of 5
      mm in full width at half maximum, bias of -4.0% to -1.9%). Shortening the total
      scan duration to 60 min had minor effects on the accuracy of VOI-based analysis
      (15 VOIs x 10 subjects); the resulting error only occasionally exceeded +/-5% in
      individual regions (n = 6 for 2-tissue-compartment model, n = 10 for VOI-based
      graphical analysis, always within +/-7.5%). Quantification accuracy was
      acceptable with scan durations of 60 and 75 min in voxelwise graphical analysis
      with spatial smoothing (mean bias in cortical regions, -8.4% to -5.9%) and
      without spatial smoothing (bias, -9.2% to -11.6%), respectively. CONCLUSION: High
      quality DVt parametric images of 18F-CPFPX can be generated by voxelwise
      graphical analysis. The noise-dependent negative bias of voxelwise graphical
      analysis is greatly reduced by spatial smoothing. A shortened scan of 60 min will
      enhance the clinical applicability of 18F-CPFPX PET.

PMID- 16455625
TI  - PET imaging of serotonin transporters with [11C]DASB: test-retest reproducibility
      using a multilinear reference tissue parametric imaging method.
AB  - Parametric imaging of serotonin transporters (SERT) with 11C-labeled 3-amino-4-(2
      dimethylaminomethyl-phenylsulfanyl)benzonitrile ([11C]DASB) PET is a useful data
      analysis tool. The purpose of this study was to evaluate the reproducibility of
      measurements of SERT binding potential (BP) and relative blood flow (R1) by a 2
      parameter multilinear reference tissue parametric imaging method (MRTM2) for
      human [11C]DASB studies. METHODS: Eight healthy subjects (3 men, 5 women; age, 26
      +/- 9 y) underwent 2 [11C]DASB PET scans separated by 1 h on the same day (dose,
      703 +/- 111 MBq). Parametric images of BP and R1 were generated by MRTM2 using
      the cerebellum as a reference region. The k'2 (clearance rate constant from the
      reference region) required by MRTM2 was estimated by the 3-parameter MRTM.
      Reproducibility of BP and R1 measurements was evaluated by calculating bias (100
      x (retest - test/test), variability (SD of the bias), and reliability (intraclass
      correlation coefficient = rho) for several representative regions of interest
      (ROIs). BP and R1 were estimated for ROI time-activity curves fitted by MRTM2 and
      were compared with those based on the parametric images. RESULTS: The test-retest
      (0.066 +/- 0.013/0.06 +/- 0.011 min(-1)) MRTM k'2 reproducibility was excellent
      with small bias (3%) and variability (6%) and high reliability (0.95). Retest BP
      values were consistently lower than those of test BP values in all regions (a
      mean negative bias of approximately 6%; P < 0.001). The test-retest BP
      variability was relatively small, ranging from 4% to 13%, with rho ranging from
      0.44 to 0.85. In contrast to BP, test-retest R1 values were similar with
      negligible bias of < or =0.1%. The test-retest R1 variability was excellent and
      smaller than that of BP ranging from 3% to 6%, with rho ranging from 0.58 to
      0.95. BP and R1 values estimated by the ROI time-activity curve-fitting method
      were slightly lower ( approximately 3% and approximately 1%, respectively) than
      those by the parametric imaging method (P < 0.001). However, the test-retest bias
      and variability of BP and R1 were very similar for both ROI and parametric
      methods. CONCLUSION: Our results suggest that [11C]DASB parametric imaging of BP
      and R1 with the noninvasive MRTM2 method is reproducible and reliable for PET
      studies of SERT.

PMID- 16455626
TI  - Brain white-matter volume loss and glucose hypometabolism precede the clinical
      symptoms of Huntington's disease.
AB  - We studied the anatomic and functional changes in various brain areas during the
      course of Huntington's disease (HD) in a large cohort of mutation-positive
      individuals (n = 71) encompassing the complete range of disability
      (presymptomatic through stage V), and in healthy controls, for the purpose of
      defining both degenerative and dysfunctional brain changes in the same subjects.
      METHODS: We used an MRI and unsupervised multiparametric segmentation procedure
      based on a relaxometric approach to measure in vivo brain volumes in 71 subjects
      with presymptomatic to advanced HD. The same population was evaluated by 18F-FDG
      PET to assess variations in brain glucose metabolism. To predict age at onset in
      unaffected mutation carriers, we considered the estimated number of years from
      each subject's age to manifested HD symptoms, for a given expanded triplet
      number. RESULTS: Age-adjusted analyses confirmed that the 71 subjects as a group,
      as well as the subgroup of 24 unaffected presymptomatic subjects at risk for HD,
      had significantly smaller gray-matter and white-matter volumes and larger
      cerebrospinal fluid volumes than did controls (P < 0.0001). In the 24
      presymptomatic subjects, we observed a significant inverse linear correlation
      between white-matter volume reduction and the estimated time to symptom onset
      (r2= 0.39; P = 0.0011). Both clinically unaffected subjects at risk for HD and
      symptomatic patients had significantly decreased glucose uptake in the cortex
      (frontal and temporal lobes) and striatum (caudate and putamen). HD subjects who
      were followed up longitudinally showed progressive white-matter reduction in the
      preclinical subjects (n = 10) and decreased glucose uptake in the cortex and
      striatum in affected (n = 21) and preclinical (n = 10) subjects. CONCLUSION:
      White-matter volume loss may precede gray-matter atrophy and may be associated
      with neuronal dysfunction in early disease.

PMID- 16455627
TI  - Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy
      of metastatic gastroenteropancreatic neuroendocrine tumors.
AB  - Radiolabeled octreotide analogs (Oct) and metaiodobenzylguanidine (MIBG) offer 2
      different approaches for imaging and targeting metastatic gastroenteropancreatic
      neuroendocrine tumors (GEP-NET). Despite successful establishment of the revised
      World Health Organization (WHO) classification, which distinguishes between low-
      and high-grade malignant GEP-NET, there is a lack of scintigraphic studies
      comparing uptake behavior on the basis of this categorization. This study aims to
      define predisposing factors of tracer uptake for both imaging principles
      implementing the updated tumor criteria of the current WHO classification.
      METHODS: Fifty-seven consecutive patients with histologically confirmed
      metastatic GEP-NET evaluated with both 111In-pentetreotide and 123I/131I-MIBG
      scintigraphy were included in this study. Intensity of tracer uptake was graded
      according to the different metastatic regions. Patients were classified as
      overall positive when avid uptake in the clinically relevant tumor lesions was
      present. Correlation was tested between the proportion of positive patients and
      tumor origin, function, and malignancy. RESULTS: Overall, 52 patients (91.2%)
      were Oct positive and 28 patients (49.1%) were MIBG positive. The proportion of
      tracer-positive patients was significantly higher (P < 0.05) in low-grade
      malignant tumors for both tracers and in functioning as well as in gastroenteral
      NET for MIBG. Five patients were negative for both tracers. None of the Oct
      negative patients proved to be MIBG positive. CONCLUSION: Oct affinity is
      observed with high frequency throughout the subgroups of metastatic GEP-NET,
      whereas corresponding MIBG uptake is overall less prevalent and more group
      dependent. Tumor differentiation significantly impacts both Oct and MIBG uptake,
      whereas functionality predisposes only for MIBG accumulation. Though clearly
      inferior to Oct-based radioimaging in most GEP-NET, MIBG achieves a remarkable
      rate of radioligand accumulation in functioning midgut enterochromaffin cell
      metastases (>80% of patients positive). These results may have implications for
      patient management and potentially for selection and performance of targeted
      therapy.

PMID- 16455628
TI  - The impact of lymphoscintigraphy technique on the outcome of sentinel node biopsy
      in 1,313 patients with cutaneous melanoma: an Italian Multicentric Study (SOLISM
      IMI).
AB  - An observational multicentric Italian trial on sentinel node biopsy (SNB) in
      melanoma patients was performed to diffuse a common SNB protocol nationwide
      (Italy). We report herein the results of this trial. The influence of some
      technical aspects on the outcome of SNB was also investigated, because a certain
      degree of variability was accepted in performing lymphoscintigraphy. METHODS:
      From January 2000 to December 2002, 1,313 consecutive patients with primary
      cutaneous melanoma (Breslow thickness, >1.0 mm or <1.0 mm but with ulceration,
      Clark level IV-V, presence of regression) were enrolled by 23 centers. One half
      to 1 mL of 99mTc-labeled human albumin colloid, at a suggested dosage of 5-15 or
      30-70 MBq, was injected intradermally, closely around the scar, the same day or
      the day before SNB. Intraoperatively, Patent blue was associated when a
      definitive wide excision of the primary was required. A positive sentinel node
      (SN) was defined when containing melanoma cells detected by either hematoxylin
      eosin or immunohistochemistry (S100 and HMB45 antibodies). All patients underwent
      regular follow-up. False-negative cases were considered when lymph node
      metastases occurred in the same lymphatic basin of SN biopsy (SNB) during follow
      up. A quality control program has been performed for the surgical procedure and
      for the histologic diagnosis. RESULTS: The SN identification rate was 99.3%. The
      axilla was the site of the SN in 52.5% of the cases. The mean number of SNs was
      2.0 (range, 1-17) and only 1 node was removed in 45.4%. The positivity and false
      negative rates were 16.9% and 14.7%, respectively (median follow-up, 31 mo). On
      multivariate analysis (logistic and linear regression) only the number of
      peritumor injections was inversely associated with the number of excised SNs (P =
      0.002), whereas none of the technical variables showed an independent impact on
      SN status when Breslow thickness was included as a control variable. CONCLUSION:
      The number of peritumor injections seems to influence the outcome of
      lymphoscintigrapy in melanoma patients undergoing SNB. If these results are
      confirmed in a controlled trial, 3 injections at least should be recommended.

PMID- 16455629
TI  - Serum concentrations of IL-2 and TNF-alpha in patients with painful bone
      metastases: correlation with responses to 89SrCl2 therapy.
AB  - We have used 89SrCl2 for the palliative treatment of painful bone metastases from
      various malignant diseases. We studied the correlation between serum interleukin
      2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) levels and the response to
      89SrCl2 therapy. METHODS: Forty-two patients (24 men and 18 women) were treated
      intravenously with 89SrCl2 at a dose of 148 MBq (4 mCi). RESULTS: The response
      rate was 33 of 42 (79%). In the control subjects, serum IL-2 concentrations were
      higher but TNF-alpha concentrations lower (P < 0.05) than in the patients with
      bone metastases. After treatment with 89SrCl2, IL-2 levels increased and TNF
      alpha levels decreased, with maximal changes at the fourth month after therapy.
      After comparing the serum levels of IL-2 and TNF-alpha between responders and
      nonresponders, we found that these variables did not differ before 89SrCl2
      therapy but differed significantly (P < 0.05) after therapy. Responders had
      higher IL-2 and lower TNF-alpha concentrations than nonresponders. A good
      correlation was found between IL-2 and TNF-alpha levels and the number of
      metastases and pain score. CONCLUSION: 89SrCl2 is effective for palliation of
      bone pain in patients with disseminated bone metastases. In addition to managing
      pain, 89SrCl2 can improve immunity and the quality of life for most patients.
      Further studies are needed to elucidate the roles of IL-2 and TNF-alpha in the
      response to 89SrCl2 therapy and to evaluate their usefulness as indicators of
      89SrCl2 efficacy.

PMID- 16455630
TI  - Targeting, toxicity, and efficacy of 2-step, pretargeted radioimmunotherapy using
      a chimeric bispecific antibody and 131I-labeled bivalent hapten in a phase I
      optimization clinical trial.
AB  - Safety, targeting, and antitumor efficacy of pretargeted radioimmunotherapy using
      anti-carcinoembryonic antigen (CEA) hMN-14 x m734 bispecific antibody (BsmAb) and
      131I-di-diethylenetriamine pentaacetic acid (DTPA)-indium hapten were evaluated
      in a phase I study performed on patients with CEA-expressing tumors. METHODS:
      Twenty-two patients with nonmedullary thyroid carcinoma (non-MTC) (group I, 13
      patients) or medullary thyroid carcinoma (MTC) (group II, 9 patients) were
      enrolled. These patients received a 75 mg/m2 (11 patients) or 40 mg/m2 (11
      patients) dose of BsmAb and escalating activities of (131)I-di-DTPA-indium 5 d
      later. Toxicity and tumor response were assessed in 20 patients who received a
      therapeutic (>2.2 GBq) hapten dose of radioactivity. RESULTS: The percentage of
      lesions detected by immunoscintigraphy after injection of the therapeutic dose of
      hapten was 70% on an anatomic-site basis. High bone uptake was relatively
      frequent. A transient grade I or II hepatic toxicity was observed in 5 patients
      (45%) injected with 75 mg/m2 of BsmAb and in 1 patient (11%) injected with 40
      mg/m2. No other nonhematologic toxicity was observed. With 75 mg/m2 of BsmAb,
      hematologic toxicity was high: 5 cases of grade III or IV leukopenia (45%) and 5
      cases of grade III or IV thrombopenia (45%). With a 40 mg/m2 dose of BsmAb,
      hematologic toxicity was reduced significantly: 3 cases of grade III or IV
      leukopenia (33%) and 1 case of grade III or IV thrombopenia (11%) (P = 0.02).
      Toxicity was significantly higher in MTC patients than in non-MTC patients (P =
      0.019). Nine cases of tumor stabilization of 3 mo to more than 12 mo were
      observed (45%), 6 in the MTC group and 3 in the non-MTC group. The rate of
      disease stabilization was significantly higher with 75 mg/m2 of BsmAb (64%) than
      with 40 mg/m2 (22%) (P = 0.04). Human antimouse antibody elevation was observed
      in 1 patient (8%) and human antihuman antibody in 4 (33%). CONCLUSION: A BsmAb
      dose of 40 mg/m2 and a 5-d interval appeared to be a better dose/schedule
      regimen, with acceptable toxicity. Under these conditions, the maximal tolerated
      activity was 3 GBq of 131I-di-DTPA-indium in MTC patients. In non-MTC patients,
      dose escalation should continue.

PMID- 16455631
TI  - 18F-FET PET compared with 18F-FDG PET and CT in patients with head and neck
      cancer.
AB  - Recent studies suggest a somewhat selective uptake of O-(2-[18F]fluoroethyl)-L
      tyrosine (FET) in cerebral gliomas and in squamous cell carcinoma (SCC) and a
      good distinction between tumor and inflammation. The aim of this study was to
      investigate the diagnostic potential of 18F-FET PET in patients with SCC of the
      head and neck region by comparing that tracer with 18F-FDG PET and CT. METHODS:
      Twenty-one patients with suspected head and neck tumors underwent 18F-FET PET,
      18F-FDG PET, and CT within 1 wk before operation. After coregistration, the
      images were evaluated by 3 independent observers and an ROC analysis was
      performed, with the histopathologic result used as a reference. Furthermore, the
      maximum standardized uptake values (SUVs) in the lesions were determined.
      RESULTS: In 18 of 21 patients, histologic examination revealed SCC, and in 2 of
      these patients, a second SCC tumor was found at a different anatomic site. In 3
      of 21 patients, inflammatory tissue and no tumor were identified. Eighteen of 20
      SCC tumors were positive for both 18F-FDG uptake and 18F-FET uptake, one 0.3-cm
      SCC tumor was detected neither with 18F-FDG PET nor with 18F-FET PET, and one 0.7
      cm SCC tumor in a 4.3-cm ulcer was overestimated as a 4-cm tumor on 18F-FDG PET
      and missed on 18F-FET PET. Inflammatory tissue was positive for 18F-FDG uptake
      (SUV, 3.7-4.7) but negative for 18F-FET uptake (SUV, 1.3-1.6). The SUVs of 18F
      FDG in SCC were significantly higher (13.0 +/- 9.3) than those of 18F-FET (4.4 +/
      2.2). The ROC analysis showed significantly superior detection of SCC with (18)F
      FET PET or 18F-FDG PET than with CT. No significant difference (P = 0.71) was
      found between 18F-FDG PET and 18F-FET PET. The sensitivity of 18F-FDG PET was
      93%, specificity was 79%, and accuracy was 83%. 18F-FET PET yielded a lower
      sensitivity of 75% but a substantially higher specificity of 95% (accuracy, 90%).
      CONCLUSION: 18F-FET may not replace 18F-FDG in the PET diagnostics of head and
      neck cancer but may be a helpful additional tool in selected patients, because
      18F-FET PET might better differentiate tumor tissue from inflammatory tissue. The
      sensitivity of 18F-FET PET in SCC, however, was inferior to that of 18F-FDG PET
      because of lower SUVs.

PMID- 16455632
TI  - Localization of primary prostate cancer with dual-phase 18F-fluorocholine PET.
AB  - This study compared 18F-fluorocholine uptake in malignant and benign areas of the
      prostate at 2 time points to determine the suitability of delayed or dual-phase
      18F-fluorocholine PET for localizing malignancy in the prostate gland. METHODS:
      Twenty-six men (15 newly diagnosed with prostate cancer, 2 with recurrent
      prostate cancer, 6 with no evidence of prostate cancer recurrence after
      treatment, and 3 with no history of prostate cancer) underwent dual-phase PET
      consisting of initial whole-body PET starting 7 min after injection of 3.3-4
      MBq/kg of 18F-fluorocholine followed by 1-h delayed PET of the pelvis. Tracer
      uptake in the prostate on the initial and delayed images was measured on a
      sextant basis. Prostate biopsy or whole-prostate histologic examination after
      radical prostatectomy was used to classify a prostate sextant as a dominant
      malignant region or probable benign region. For each sextant, a retention index
      based on the measured maximum standardized uptake value (SUVmax) was calculated
      on the initial and delayed images. In 15 prostates with both benign and malignant
      sextants on histologic examination, a malignant-to-benign ratio of SUVmax was
      also calculated for each time point. RESULTS: A dominant malignant region was
      found in 17 subjects, and a probable benign region was found in 24 subjects. The
      mean SUVmax for dominant malignant regions increased significantly between
      initial and delayed scans, from 7.6 to 8.6 (mean retention index, +14%; 95%
      confidence interval, 6%-22%; P = 0.002). The mean SUVmax for probable benign
      regions decreased significantly between initial and delayed scans, from 4.8 to
      3.9 (mean retention index, -17%; 95% confidence interval, -10% to -23%, P <
      0.001). The mean malignant-to-benign ratio increased significantly, from 1.4 on
      the initial scan to 1.8 on the delayed scan (P = 0.003). The areas under the
      receiver operating characteristic curves for distinguishing dominant malignant
      regions from probable benign regions based on initial SUVmax, delayed SUVmax, and
      retention index were 0.81, 0.92, and 0.93, respectively. CONCLUSION: On dual
      phase PET of the prostate, areas of malignancy consistently demonstrated stable
      or increasing 18F-fluorocholine uptake, whereas most areas containing benign
      tissue demonstrated decreasing uptake. Delayed or dual-phase imaging after
      injection of 18F-fluorocholine may improve the performance of 18F-fluorocholine
      PET for localizing malignant areas of the prostate.

PMID- 16455633
TI  - Visualization of telomerase reverse transcriptase (hTERT) promoter activity using
      a trimodality fusion reporter construct.
AB  - Our goal was to noninvasively measure chemotherapy-induced changes in the
      expression of critical tumor growth genes. To achieve this goal, we used
      radionuclide and optical methods to measure changes in human telomerase reverse
      transcriptase (hTERT) gene expression in tumor cells before and after 5
      fluorouracil treatment. METHODS: A fusion reporter construct, containing
      humanized Renilla luciferase (hrl, for bioluminescent imaging), monomeric red
      fluorescence protein 1 (mrfp1, for fluorescent imaging), and a truncated
      thymidine kinase (ttk, for imaging of radiolabeled acycloguanosines), was placed
      under the control of hTERT promoter fragments. These constructs were introduced
      into tumor cell lines with and without hTERT expression. Transfected cells were
      treated with 5-fluorouracil, a chemotherapeutic that decreases hTERT gene
      expression, and treatment-induced changes in hTERT promoter activity were imaged.
      RESULTS: When the fusion construct is introduced into cell lines that express
      hTERT, all 3 reporter systems are highly expressed and hTERT promoter activity
      can be visualized. Cell lines lacking hTERT transcription show no significant
      reporter expression. Decreases in hTERT gene expression caused by 5-fluorouracil
      treatment could be visualized in living 293T cells by both fluorescent microscopy
      and bioluminescent imaging. CONCLUSION: hTERT promoter activity can be monitored
      by 1 radionuclide and 2 optical reporter systems using a single reporter
      construct. This in vitro study provides evidence that our multimodality reporter
      construct can be used to study the expression of a critical tumor growth gene in
      living subjects.

PMID- 16455634
TI  - Bone marrow transplantation nephropathy after an intensified conditioning regimen
      with radioimmunotherapy and allogeneic stem cell transplantation.
AB  - Intensification of the conditioning regimen with a radioactively labeled anti
      CD66 antibody is feasible before allogeneic stem cell transplantation. The use of
      radioimmunotherapy may deliver a significant dose of radiation to the kidneys. We
      therefore studied the incidence and clinical picture of bone marrow
      transplantation (BMT) nephropathy in our patients receiving radioimmunotherapy
      before allogeneic stem cell transplantation. METHODS: This study was a clinical
      trial of 114 consecutive patients who received conditioning with a radiolabeled
      anti-CD66 antibody-188Re (n = 93) or 90Y (n = 21)-between 1998 and 2003. RESULTS:
      Although BMT nephropathy has developed in none of the patients in the [90Y]anti
      CD66 group, 6 of 93 patients receiving [188Re]anti-CD66 presented with signs of
      BMT nephropathy at a median of 11.5 mo after stem cell transplantation. The
      absorbed renal dose was significantly lower in the 90Y group (4 vs. 7 Gy, P <
      0.0001). Of the patients receiving [188Re]anti-CD66 who are alive, BMT
      nephropathy developed in 19% (6/32). Five of 6 patients with BMT nephropathy
      received total-body irradiation. The patients presented with elevated serum
      creatinine, proteinuria, anemia, hypertension, and signs of microangiopathy. All
      6 patients in whom BMT nephropathy has developed are alive at a median follow-up
      of 58 mo after stem cell transplantation, and 1 patient has entered a dialysis
      program. CONCLUSION: BMT nephropathy appears to be a significant problem after
      allogeneic stem cell transplantation with intensified conditioning using the
      188Re-labeled anti-CD66 applied in this study, particularly when combined with
      total-body irradiation.

PMID- 16455635
TI  - The detection of bone metastases in patients with high-risk prostate cancer:
      99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F
      fluoride PET, and 18F-fluoride PET/CT.
AB  - The aim of this study was to compare the detection of bone metastases by 99mTc
      methylene diphosphonate (99mTc-MDP) planar bone scintigraphy (BS), SPECT, 18F
      Fluoride PET, and 18F-Fluoride PET/CT in patients with high-risk prostate cancer.
      METHODS: In a prospective study, BS and 18F-Fluoride PET/CT were performed on the
      same day in 44 patients with high-risk prostate cancer. In 20 of the latter
      patients planar BS was followed by single field-of-view (FOV) SPECT and in 24
      patients by multi-FOV SPECT of the axial skeleton. Lesions were interpreted
      separately on each of the 4 modalities as normal, benign, equivocal, or
      malignant. RESULTS: In patient-based analysis, 23 patients had skeletal
      metastatic spread (52%) and 21 did not. Categorizing equivocal and malignant
      interpretation as suggestive for malignancy, the sensitivity, specificity,
      positive predictive value, and negative predictive value of planar BS were 70%,
      57%, 64%, and 55%, respectively, of multi-FOV SPECT were 92%, 82%, 86%, and 90%,
      of (18)F-Fluoride PET were 100%, 62%, 74%, and 100%, and of 18F-Fluoride PET/CT
      were 100% for all parameters. Using the McNemar test, 18F-Fluoride PET/CT was
      statistically more sensitive and more specific than planar or SPECT BS (P < 0.05)
      and more specific than 18F-Fluoride PET (P < 0.001). SPECT was statistically more
      sensitive and more specific than planar BS (P < 0.05) but was less sensitive than
      18F-Fluoride PET (P < 0.05). In lesion-based analysis, 156 lesions with increased
      uptake of 18F-Fluoride were assessed. Based on the corresponding appearance on
      CT, lesions were categorized by PET/CT as benign (n = 99), osteoblastic
      metastasis (n = 46), or equivocal when CT was normal (n = 11). Of the 156 18F
      Fluoride lesions, 81 lesions (52%), including 34 metastases, were overlooked with
      normal appearance on planar BS. SPECT identified 62% of the lesions overlooked by
      planar BS. 18F-Fluoride PET/CT was more sensitive and more specific than BS (P <
      0.001) and more specific than PET alone (P < 0.001). CONCLUSION: 18F-Fluoride
      PET/CT is a highly sensitive and specific modality for detection of bone
      metastases in patients with high-risk prostate cancer. It is more specific than
      18F-Fluoride PET alone and more sensitive and specific than planar and SPECT BS.
      Detection of bone metastases is improved by SPECT compared with planar BS and by
      18F-Fluoride PET compared with SPECT. This added value of 18F-Fluoride PET/CT may
      beneficially impact the clinical management of patients with high-risk prostate
      cancer.

PMID- 16455636
TI  - Standard PET/CT of the chest during shallow breathing is inadequate for
      comprehensive staging of lung cancer.
AB  - The incidence of malignancy associated with subcentimeter pulmonary nodules
      (micronodules) in patients with malignant disease has been reported to be as high
      as 58%. Thus, detection of small lung nodules is important for appropriate
      staging of lung cancer. Because of respiratory motion, small parenchymal lung
      lesions can be missed on CT acquired during shallow breathing. Micronodules are
      usually too small to be characterized reliably with 18F-FDG PET. We aimed to
      determine the incidence of missed pulmonary micronodules on PET/CT studies
      acquired during shallow breathing. METHODS: The study included 142 consecutive
      cancer patients (62 male and 80 female; mean age, 54 y) who underwent whole-body
      PET/CT during shallow breathing and breath-hold CT of the chest during maximal
      inspiration. CT findings were reviewed independently, and noncalcified nodules
      missed on the shallow-breathing scan were evaluated for size, location, and
      metabolic activity. RESULTS: Breath-hold chest CT detected an additional 125
      parenchymal lung nodules (mean size, 3.4 +/- 1.6 mm; range, 1-9 mm) in 48 (34%)
      of the 142 patients. In these patients, 3 nodules, on average, were missed during
      shallow breathing. In 18 patients (13%), micronodules were identified exclusively
      on breath-hold images. None of the missed nodules demonstrated 18F-FDG uptake.
      CONCLUSION: Acquisition of standard PET/CT chest images during shallow breathing
      is inadequate for comprehensive cancer staging.

PMID- 16455637
TI  - Brain receptor imaging.
AB  - Receptors have a prominent role in brain function, as they are the effector sites
      of neurotransmission at the postsynaptic membrane, have a regulatory role on
      presynaptic sites for transmitter reuptake and feedback, and are modulating
      various functions on the cell membrane. Distribution, density, and activity of
      receptors in the brain can be visualized by radioligands labeled for SPECT and
      PET, and the receptor binding can be quantified by appropriate tracer kinetic
      models, which can be modified and simplified for particular application.
      Selective radioligands are available for the various transmitter systems, by
      which the distribution of these receptors in the normal brain and changes in
      receptor binding during various physiologic activities or resulting from
      pathologic conditions can be visualized. The quantitative imaging for several
      receptors has gained clinical importance-for example, dopamine (D2)) receptors
      for differential diagnosis of movement disorders and for assessment of receptor
      occupancy by neuroleptics drugs; serotonin (5-hydroxytryptamine, 5-HT) receptors
      and the 5-HT transporter in affective disorders and for assessment of activity of
      antidepressants; nicotinic receptors and acetylcholinesterase as markers of
      cognitive and memory impairment; central benzodiazepine-binding sites at the
      gamma-aminobutyric acid A (GABAA) receptor complex as markers of neuronal
      integrity in neurodegenerative disorders, epilepsy, and stroke and as the site of
      action of benzodiazepines; peripheral benzodiazepine receptors as indicators of
      inflammatory changes; opioid receptors detecting increased cortical excitability
      in focal epilepsy but also affected in perception of and emotional response to
      pain; and several receptor systems affected in drug abuse and craving. Further
      studies of the various transmitter/receptor systems and their balance and
      infraction will improve our understanding of complex brain functions and will
      provide more insight into the pathophysiology of neurologic and psychiatric
      disease interaction.

PMID- 16455638
TI  - Biodistribution and radiation dosimetry of the dopamine D2 ligand 11C-raclopride
      determined from human whole-body PET.
AB  - Whole-body radiation dosimetry of 11C-raclopride was performed in healthy human
      volunteers. METHODS: Subjects (n = 6) were scanned with PET. Subjects received
      single-bolus injections of 11C-raclopride (S-(-)-3,5-dichloro-N-[(1-ethyl-2
      pyrrolidinyl)]methyl-2-hydroxy-6-methoxybenzamide) (533 +/- 104 MBq) and were
      scanned for approximately 110 min with a 2-dimensional whole-body protocol.
      Regions of interest were placed over all visually identifiable organs and time
      activity curves were generated. Residence times were computed as the area under
      the curve of the time-activity curves, normalized to injected activities and
      standard values of organ volumes. Absorbed doses were computed according to the
      MIRD schema with MIRDOSE3.1 software. RESULTS: Organs with the highest radiation
      burden were gallbladder wall, small intestine, liver, and urinary bladder wall.
      CONCLUSION: On the basis of the estimated absorbed dose, the maximum allowable
      single study dose under U.S. federal regulations for studies performed under
      Radiation Drug Research Committee is 1.58 GBq (42.8 mCi). This is still
      considerably higher than the doses of 11C-raclopride commonly used in research
      PET (370-555 MBq).

PMID- 16455639
TI  - RENEX: an expert system for the interpretation of 99mTc-MAG3 scans to detect
      renal obstruction.
AB  - A renal expert system (RENEX) has been developed to assist physicians detect
      renal obstruction in patients undergoing pre- and postfurosemide 99mTc
      mercaptoacetyltriglycine (99mTc-MAG3) scans. RENEX uses quantitative parameters
      extracted from the dynamic renal scan data and heuristic rules in the form of a
      knowledge base (KB) obtained from expert interpreters to conclude whether a
      kidney is obstructed. METHODS: Normal limits were established for 47 quantitative
      parameters extracted from the 99mTc-MAG3 scans of 100 potential renal donors.
      From these data the domain expert estimated 5 boundary conditions for each
      parameter: (i) definitely abnormal, (ii) probably abnormal, (iii) equivocal, (iv)
      probably normal, and (v) definitely normal. A sigmoid-type curve was then
      generated from these 5 boundary conditions, creating a parameter knowledge
      library used for converting the value of a prospective patient's individual
      quantitative parameters to a certainty factor (CF). Sixty heuristic rules were
      extracted from the domain expert to generate the KB for detecting obstruction. A
      forward-chaining inference engine was developed using the MYCIN combinatories (an
      approximation of Bayes theorem) to determine obstruction. A justification engine
      was implemented, which recorded the sequence of each rule that was fired and the
      current CF value of all input and output parameters at the time of instantiation
      to track and justify the logic of the conclusions. The entire system was fine
      tuned and tested using a pilot group of 32 patients (11 males, 21 females; mean
      age, 56.8 +/- 17.2 y; 63 kidneys) deemed by an expert panel to have 41
      unobstructed kidneys, 13 obstructed kidneys,and 9 equivocal findings. RESULTS:
      RENEX agreed with the expert panel in 92% (12/13) of the obstructed kidneys, 93%
      (38/41) of the unobstructed kidneys, and 78% (7/9) of the kidneys interpreted as
      equivocal for obstructions. Processing time per patient was practically
      instantaneous using a 3.0-GHz personal computer programmed using interactive data
      language. CONCLUSION: We have developed a renal expert system for detecting renal
      obstruction using pre- and postfurosemide 99mTc-MAG3 renal scans, at a
      standardized expert level. These encouraging preliminary results warrant a
      prospective study in a large population of patients with and without renal
      obstruction to establish the diagnostic performance of this system.

PMID- 16455640
TI  - Minimally invasive method of determining blood input function from PET images in
      rodents.
AB  - For cardiovascular research on rodents, small-animal PET has limitations because
      of the inherent spatial resolution of the system and because of cardiac motion. A
      factor analysis (FA) technique for extracting the blood input function and
      myocardial time-activity curve from dynamic small-animal PET images of the rodent
      heart has been implemented to overcome these limitations. METHODS: Six Sprague
      Dawley rats and 6 BALB/c mice underwent dynamic imaging with 18F-FDG (n = 6) and
      1-11C-acetate (n = 6). From the dynamic images, blood input functions and
      myocardial time-activity curves were extracted by the FA method. The accuracy of
      input functions derived by the FA method was compared with that of input
      functions determined from serial blood samples, and the correlation coefficients
      were calculated. RESULTS: Factor images (right ventricle, left ventricle, and
      myocardium) were successfully extracted for both 18F-FDG and 1-11C-acetate in
      rats. The correlation coefficients for the input functions were 0.973 for 18F-FDG
      and 0.965 for 1-11C-acetate. In mice, the correlation coefficients for the input
      functions were 0.930 for 18F-FDG and 0.972 for 1-11C-acetate. CONCLUSION: The FA
      method enables minimally invasive extraction of accurate input functions and
      myocardial time-activity curves from dynamic microPET images of rodents without
      the need to draw regions of interest and without the possible complications of
      surgery and repeated blood sampling.

PMID- 16455641
TI  - Initial infarct size predicts subsequent cardiac remodeling in the rat infarct
      model: an in vivo serial pinhole gated SPECT study.
AB  - The rat infarct model is widely used to study left ventricular (LV) remodeling, a
      main cause of heart failure characterized by progressive LV dilatation. Using
      pinhole collimators and advances in data processing, gated SPECT was recently
      adapted to image the rat heart. The aim of this study was to assess this new
      imaging technique for predicting and quantifying variable LV remodeling from the
      rat infarct model. METHODS: Pinhole 99mTc-sestamibi gated SPECT was validated for
      determining LV volume and identifying the necrotic and nonviable LV segments
      (<50% of 99mTc-sestamibi uptake) in rats, and it was applied to monitor rat LV
      function from 48 h to 12 wk after occlusion of the left anterior descending
      coronary artery (LAD) (n = 20) or sham operation (n = 9). RESULTS: In LAD
      occluded rats, 48-h SPECT necrosis was large (> or =30% LV) in 6, limited (<30%
      LV) in 6, and undetectable in 8. End-diastolic volume of LAD-occluded rats was
      equivalent to that of sham-operated rats at 48 h (320 +/- 84 microL vs. 293 +/-
      48 microL; not significant) but became higher at 12 wk (501 +/- 191 microL vs.
      343 +/- 46 microL; P = 0.01). The follow-up increase in end-diastolic volume,
      which reflects the remodeling process, was closely related to the initial extent
      of necrosis revealed by the SPECT images (P < 0.001; R2= 0.85). This increase was
      limited in sham-operated rats (50 +/- 15 microL) and in the LAD-occluded rats
      with undetectable necrosis (55 +/- 35 microL) but it was around 3- and 7-fold
      higher in the LAD-occluded rats with limited (165 +/- 57 microL) and large (366
      +/- 113 microL) necrosis, respectively. CONCLUSION: The variable LV remodeling
      documented after coronary occlusion in rats closely relates to the variable
      extent of necrosis provided by this model. Pinhole gated SPECT allows this
      remodeling to be predicted and quantified and, hence, constitutes an original
      tool for the experiments scheduled on the rat infarct model.

PMID- 16455642
TI  - PET imaging of brain 5-HT1A receptors in rat in vivo with 18F-FCWAY and
      improvement by successful inhibition of radioligand defluorination with
      miconazole.
AB  - 18F-FCWAY (18F-trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazin-1-yl)ethyl]-N
      (2-pyridyl)cyclohexanecarboxamide) is useful in clinical research with PET for
      measuring serotonin 1A (5-HT1A) receptor densities in brain regions of human
      subjects but has significant bone uptake of radioactivity due to defluorination.
      The uptake of radioactivity in skull compromises the accuracy of measurements of
      5-HT1A receptor densities in adjacent areas of brain because of spillover of
      radioactivity through the partial-volume effect. Our aim was to demonstrate with
      a rat model that defluorination of 18F-FCWAY may be inhibited in vivo to improve
      its applicability to measuring brain regional 5-HT1A receptor densities. METHODS:
      PET of rat head after administration of 18F-FCWAY was used to confirm that the
      distribution of radioactivity measured in brain is dominated by binding to 5-HT1A
      receptors and to reveal the extent of defluorination of 18F-FCWAY in vivo as
      represented by radioactivity (18F-fluoride ion) uptake in skull. Cimetidine,
      diclofenac, and miconazole, known inhibitors of CYP450 2EI, were tested for the
      ability to inhibit defluorination of 18F-FCWAY in rat liver microsomes in vitro.
      The effects of miconazole treatment of rats on skull radioactivity uptake and, in
      turn, its spillover on brain 5-HT1A receptor imaging were assessed by PET with
      venous blood analysis. RESULTS: PET confirmed the potential of 18F-FCWAY to act
      as a radioligand for 5-HT1A receptors in rat brain and also revealed extensive
      defluorination. In rat liver microsomes in vitro, defluorination of 18F-FCWAY was
      almost completely inhibited by miconazole and, to a less extent, by diclofenac.
      In PET experiments, treatment of rats with miconazole nitrate (60 mg/kg
      intravenously) over the 45-min period before administration of 18F-FCWAY almost
      obliterated defluorination and bone uptake of radioactivity. Also, brain
      radioactivity almost doubled while the ratio of radioactivity in receptor-rich
      ventral hippocampus to that in receptor-poor cerebellum almost tripled to 14. The
      plasma half-life of radioligand was also extended by miconazole treatment.
      CONCLUSION: Miconazole treatment, by eliminating defluorination of 18F-FCWAY,
      results in effective imaging of brain 5-HT1A receptors in rat. 18F-FCWAY PET in
      miconazole-treated rats can serve as an effective platform for investigating 5
      HT1A receptors in rodent models of neuropsychiatric conditions or drug action.

PMID- 16455643
TI  - In vitro modeling of the clinical interactions between octreotide and 111In
      pentetreotide: is there evidence of somatostatin receptor downregulation?
AB  - Some authors have suggested that chronic octreotide use enhances the efficiency
      of radiolabeled somatostatin receptor (sst) imaging. Conversely, desensitization
      of sst on tumor tissue (tachyphylaxis) may occur occasionally in patients on
      chronic octreotide therapy. Assuming that chronic exposure to octreotide induces
      tachyphylaxis, we hypothesized that chronic exposure of sst subtype 2 (sst2)
      expressing cells to octreotide would downregulate binding of 111In-pentetreotide
      to sst and that this downregulation would be due to a reduction in the gene copy
      number for sst2. METHODS: The clinical scenarios of acute (24 h) and chronic (2
      wk) octreotide use, followed by either nuclear imaging exposure (8.6 pmol/L) or
      therapeutic exposure (510 pmol/L) to (111)In-pentetreotide, were modeled in
      vitro. Receptor binding in IMR-32 human neuroblastoma cells (high sst2
      expression) and PANC-1 human pancreatic cancer cells (no detectable sst2
      expression) was evaluated. Gene copy numbers for sst subtypes 1-5 in IMR-32 cells
      were determined by quantitative polymerase chain reaction. RESULTS: Acute or
      chronic octreotide exposure at low or high doses did not significantly alter sst2
      gene copy numbers or binding of either the diagnostic dose or the therapeutic
      dose of 111In-pentetreotide. CONCLUSION: In vitro exposure of cells to low or
      high doses of octreotide for 1-14 d does not result in the development of either
      tachyphylaxis or upregulation of sst as assessed by changes in gene expression or
      in high-affinity binding.

PMID- 16455644
TI  - Initial mechanistic studies of antisense targeting in cells.
AB  - The continued development of antisense targeting will require a better
      understanding of the mechanism. METHODS: We performed initial studies of the
      mechanism of intracellular antisense targeting through measurements of in situ
      transcription, immunofluorescence, reverse transcription polymerase chain
      reaction (RT-PCR), 32P-labeled uridine-5'-triphosphate (alpha-32P-UTP)
      incorporation, nuclear accumulations of 99mTc-labeled DNAs, and messenger RNA
      (mRNA) transcription rate. As reported earlier, an antisense DNA against the mdr1
      mRNA coding for P-glycoprotein (Pgp) and its sense DNA control were used in KB-G2
      (Pgp++) cells. RESULTS: Definitive evidence for antisense targeting was obtained
      by in situ transcription showing complementary DNA elongation in cells exposed to
      antisense DNA, acting therefore as an intracellular PCR primer of mdr1 mRNA, but
      not in cells exposed to sense DNA. Immunofluorescence staining showed higher
      accumulations of antisense versus sense DNAs in KB-G2 cells. Transnuclear
      migration was confirmed by higher accumulations in the nucleus compared with the
      cytoplasm in cells incubated with 99mTc-labeled antisense DNA. However, the
      observed specific accumulations of antisense DNAs of about 10(6) per cell over 10
      h could not be explained by a feedback mechanism upregulating transcription in
      cells exposed to antisense DNA as no increase in mRNA levels was detected by both
      RT-PCR and 32P-UTP in these cells. To explore an alternative hypothesis, a novel
      approach using 99mTc-labeled antisense DNA as a probe of total mRNA from cells
      previously saturated with unlabeled antisense DNA was used to estimate the
      transcription rate. Compared with controls, mdr1 mRNA levels were found to be
      initially low after saturation and to recover at about 2,000 copies per minute
      per cell. If persistent, this transcription rate would provide 10(6) mRNAs in 10
      h. CONCLUSION: The results of all studies are consistent with antisense as the
      mechanism of targeting. Though a feedback mechanism leading to upregulation of
      mRNA transcription is an unlikely explanation for the high specific
      accumulations, our results may be explained if antisense DNAs are targeting mdr1
      mRNAs produced at high transcription rates. If the target is primarily pre-mRNA
      in the nucleus rather than mature mRNA in the cytoplasm, this would provide as
      well an explanation for the observed migration of 99mTc-labeled antisense DNA
      into the nucleus.

PMID- 16455645
TI  - Activation of family C G-protein-coupled receptors by the tripeptide glutathione.
AB  - The Family C G-protein-coupled receptors include the metabotropic glutamate
      receptors, the gamma-aminobutyric acid, type B (GABAB) receptor, the calcium
      sensing receptor (CaSR), which participates in the regulation of calcium
      homeostasis in the body, and a diverse group of sensory receptors that encompass
      the amino acid-activated fish 5.24 chemosensory receptor, the mammalian T1R taste
      receptors, and the V2R pheromone receptors. A common feature of Family C
      receptors is the presence of an amino acid binding site. In this study, a
      preliminary in silico analysis of the size and shape of the amino acid binding
      pocket in selected Family C receptors suggested that some members of this family
      could accommodate larger ligands such as peptides. Subsequent screening and
      docking experiments identified GSH as a potential ligand or co-ligand at the fish
      5.24 receptor and the rat CaSR. These in silico predictions were confirmed using
      an [3H]GSH radioligand binding assay and a fluorescence-based functional assay
      performed on wild-type and chimeric receptors. Glutathione was shown to act as an
      orthosteric agonist at the 5.24 receptor and as a potent enhancer of calcium
      induced activation of the CaSR. Within the mammalian receptors, this effect was
      specific to the CaSR because GSH neither directly activated nor potentiated other
      Family C receptors including GPRC6A (the putative mammalian homolog of the fish
      5.24 receptor), the metabotropic glutamate receptors, or the GABAB receptor. Our
      findings reveal a potential new role for GSH and suggest that this peptide may
      act as an endogenous modulator of the CaSR in the parathyroid gland where this
      receptor is known to control the release of parathyroid hormone, and in other
      tissues such as the brain and gastrointestinal tract where the role of the
      calcium receptor appears to subserve other, as yet unknown, physiological
      functions.

PMID- 16455646
TI  - TLR1- and TLR6-independent recognition of bacterial lipopeptides.
AB  - Bacterial cell walls contain lipoproteins/peptides, which are strong modulators
      of the innate immune system. Triacylated lipopeptides are assumed to be
      recognized by TLR2/TLR1-, whereas diacylated lipopeptides use TLR2/TLR6
      heteromers for signaling. Following our initial discovery of TLR6-independent
      diacylated lipopeptides, we could now characterize di- and triacylated
      lipopeptides (e.g. Pam(2)C-SK(4), Pam(3)C-GNNDESNISFKEK), which have stimulatory
      activity in TLR1- and in TLR6-deficient mice. Furthermore, for the first time, we
      present triacylated lipopeptides with short length ester-bound fatty acids (like
      PamOct(2)C-SSNASK(4)), which induce no response in TLR1-deficient cells. No
      differences in the phosphorylation of MAP kinases by lipopeptide analogs having
      different TLR2-coreceptor usage were observed. Blocking experiments indicated
      that different TLR2 heteromers recognize their specific lipopeptide ligands
      independently from each other. In summary, a triacylation pattern is necessary
      but not sufficient to render a lipopeptide TLR1-dependent, and a diacylation
      pattern is necessary but not sufficient to render a lipopeptide TLR6-dependent.
      Contrary to the current model, distinct lipopeptides are recognized by TLR2 in a
      TLR1- and TLR6-independent manner.

PMID- 16455647
TI  - Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide
      linked HLA-G dimer.
AB  - HLA-G is a nonclassical major histocompatibility complex class I (MHCI) molecule,
      which is expressed in trophoblasts and confers immunological tolerance in the
      maternal-fetal interface by binding to leukocyte Ig-like receptors (LILRs, also
      called as LIR/ILT/CD85) and CD8. HLA-G is expressed in disulfide-linked dimer
      form both in solution and at the cell surface. Interestingly, MHCI dimer
      formations have been involved in pathogenesis and T cell activation. The
      structure and receptor binding characteristics of MHCI dimers have never been
      evaluated. Here we performed binding studies showing that the HLA-G dimer
      exhibited higher overall affinity to LILRB1/2 than the monomer by significant
      avidity effects. Furthermore, the cell reporter assay demonstrated that the dimer
      formation remarkably enhanced the LILRB1-mediated signaling at the cellular
      level. We further determined the crystal structure of the wild-type dimer of HLA
      G with the intermolecular Cys(42)-Cys(42) disulfide bond. This dimer structure
      showed the oblique configuration to expose two LILR/CD8-binding sites upward from
      the membrane easily accessible for receptors, providing plausible 1:2 (HLA-G
      dimer:receptors) complex models. These results indicated that the HLA-G dimer
      conferred increased avidity in a proper structural orientation to induce
      efficient LILR signaling, resulting in the dominant immunosuppressive effects.
      Moreover, structural and functional implications for other MHCI dimers observed
      in activated T cells and the pathogenic allele, HLA-B27, are discussed.

PMID- 16455648
TI  - Proteolytic regulation of nuclear factor of activated T (NFAT) c2 cells and NFAT
      activity by caspase-3.
AB  - The nuclear factor of activated T (NFAT) cell family of transcription factors is
      important in regulating the expression of a broad array of genes, including
      cytokines, T cell surface receptors, and other transcription factors. NFATc1 and
      NFATc2 are two principal NFAT members that are expressed in peripheral T cells.
      Levels of NFAT expression in T cells are partly transcriptionally regulated, but
      less is understood regarding their post-transcriptional control. We show here
      that NFATc1 and NFATc2 are rapidly degraded in apoptotic T cells. NFATc2 is
      highly sensitive to cleavage by caspase-3, whereas NFATc1 is only weakly
      sensitive to caspase-3 or caspase-8. Two potential caspase-3 cleavage sites were
      identified in the N-terminal transactivation domain. These sites were confirmed
      by in vitro caspase cleavage assays. Abolition of NFATc2 cleavage by mutation of
      these two cleavage sites resulted in augmented NFAT transcriptional activity.
      Furthermore, NFAT activity could be augmented in wild-type effector T cells by
      inhibition of caspase activity. Of particular interest was that non-apoptotic T
      cells from cellular FLIP long transgenic (c-FLIP(L)-Tg) mice that manifest
      elevated caspase activity have greatly reduced levels of NFATc2 protein and NFAT
      transcriptional activity. Our findings reveal a new post-transcriptional
      regulation of NFATc2 that operates, not only during apoptosis, but also in non
      apoptotic effector T cells.

PMID- 16455649
TI  - Identification of a novel protein with a role in lipoarabinomannan biosynthesis
      in mycobacteria.
AB  - All species of Mycobacteria synthesize distinctive cell walls that are rich in
      phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan
      (LAM). PIM glycolipids, having 2-4 mannose residues, can either be channeled into
      polar PIM species (with 6 Man residues) or hypermannosylated to form LM and LAM.
      In this study, we have identified a Mycobacterium smegmatis gene, termed lpqW,
      that is required for the conversion of PIMs to LAM and is highly conserved in all
      mycobacteria. A transposon mutant, Myco481, containing an insertion near the 3'
      end of lpqW exhibited altered colony morphology on complex agar medium. This
      mutant was unstable and was consistently overgrown by a second mutant,
      represented by Myco481.1, that had normal growth and colony characteristics.
      Biochemical analysis and metabolic labeling studies showed that Myco481
      synthesized the complete spectrum of apolar and polar PIMs but was unable to make
      LAM. LAM biosynthesis was restored to near wild type levels in Myco481.1.
      However, this mutant was unable to synthesize the major polar PIM (AcPIM6) and
      accumulated a smaller intermediate, AcPIM4. Targeted disruption of the lpqW gene
      and complementation of the initial Myco481 mutant with the wild type gene
      confirmed that the phenotype of this mutant was due to loss of LpqW. These
      studies suggest that LpqW has a role in regulating the flux of early PIM
      intermediates into polar PIM or LAM biosynthesis. They also suggest that AcPIM4
      is the likely branch point intermediate in polar PIM and LAM biosynthesis.

PMID- 16455650
TI  - Importance of the different proteolytic sites of the proteasome and the efficacy
      of inhibitors varies with the protein substrate.
AB  - The relative importance of the different proteolytic sites in mammalian
      proteasomes in protein degradation has not been studied systematically.
      Nevertheless, it is widely assumed that inhibition of the chymotrypsin-like site,
      the primary target of the proteasome inhibitors used in research and cancer
      therapy, reflects the degree of inhibition of protein breakdown. Here we
      demonstrate that selective inactivation of the chymotrypsin-like site reduced
      degradation of model proteins by pure 26 S proteasomes by only 11-50% and
      decreased only slightly the breakdown of proteins in HeLa cells. Inactivation of
      the caspase-like site decreased breakdown of model proteins by 12-22% and of the
      trypsin-like site by 3-35%. The relative contributions of these different sites
      depended on the protein substrate, and the importance of the trypsin-like sites
      depended on the substrate's content of basic residues. Simultaneous inhibition of
      the chymotrypsin-like and the caspase- or trypsin-like sites was needed to reduce
      degradation by >50%. Thus, 1) all three types of active sites contribute
      significantly to protein breakdown, 2) their relative importance varies widely
      with the substrate, 3) assaying the chymotrypsin-like activity overestimates the
      actual reduction in protein degradation, and 4) inhibition of multiple sites is
      required to markedly decrease proteolysis.

PMID- 16455651
TI  - A growth-suppressive function for the c-fes protein-tyrosine kinase in colorectal
      cancer.
AB  - The human c-fes locus encodes a non-receptor protein-tyrosine kinase implicated
      in myeloid, vascular endothelial, and neuronal cell differentiation. A recent
      analysis of the tyrosine kinome in colorectal cancer identified c-fes as one of
      only seven genes with consistent kinase domain mutations. Although four mutations
      were identified (M704V, R706Q, V743M, S759F), the consequences of these mutations
      on Fes kinase activity were not explored. To address this issue, Fes mutants with
      these substitutions were co-expressed with STAT3 in human 293T cells.
      Surprisingly, the M704V, R706Q, and V743M mutations substantially reduced Fes
      autophosphorylation and STAT3 Tyr-705 phosphorylation compared with wild-type
      Fes, whereas S759F had little effect. These mutations had a similar impact on Fes
      kinase activity in a yeast expression system, suggesting that they inhibit Fes by
      affecting kinase domain structure. We have also demonstrated for the first time
      that endogenous Fes is strongly expressed at the base of colonic crypts where it
      co-localizes with epithelial cells positive for the progenitor cell marker
      Musashi-1. In contrast to normal colonic epithelium, Fes expression was reduced
      or absent in colon tumor sections from most individuals. Fes protein levels were
      also low or absent in a panel of human colorectal cancer cell lines, including HT
      29 and HCT 116 cells. Introduction of Fes into these lines with a recombinant
      retrovirus suppressed their growth in soft agar. Together, our findings strongly
      implicate the c-Fes protein-tyrosine kinase as a tumor suppressor rather than a
      dominant oncogene in colorectal cancer.

PMID- 16455652
TI  - Differentiation of carbazole catabolic operons by replacement of the regulated
      promoter via transposition of an insertion sequence.
AB  - The carbazole catabolic car operons from Pseudomonas resinovorans CA10 and
      Janthinobacterium sp. J3 have nearly identical nucleotide sequences in their
      structural and intergenic regions but not in their flanking regions.
      Transposition of ISPre1 from the anthranilate catabolic ant operon located an
      inducible promoter Pant upstream of the carCA10 operon, which is regulated by the
      AraC/XylS family activator AntR in response to anthranilate. The transposed Pant
      drives transcription of the carCA10 operon, which is composed of the car
      AaAaBaBbCAcAdDFECA10 structural genes. Transcriptional fusion truncating Pant
      upstream of carAaCA10 resulted in constitutive luciferase expression. Primer
      extension analysis identified a transcription start point of the constitutive
      mRNA of the carCA10 operon at 385 nucleotides upstream of the carAaCA10
      translation start point, and the PcarAa promoter was found. On the other hand, a
      GntR family regulatory gene carRJ3 is divergently located upstream of the carJ3
      operon. The Pu13 promoter, required for inducible transcription of the carJ3
      operon in the presence of carbazole, was identified in the region upstream of
      carAaJ3, which had been replaced with the Pant promoter in the carCA10 operon.
      Deletion of carRJ3 from a transcriptional fusion resulted in high level
      constitutive expression from Pu13. Purified CarRJ3 protein bound at two operator
      sequences OI and OII, showing that CarRJ3 directly represses Pu13 in the absence
      of its inducer, which was identified as 2-hydroxy-6-oxo-6-(2'-aminophenyl)hexa
      2,4-dienoate, an intermediate of the carbazole degradation pathway.

PMID- 16455653
TI  - ADAM12 is a four-leafed clover: the excised prodomain remains bound to the mature
      enzyme.
AB  - The ADAMs (a disintegrin and metalloprotease) comprise a family of multidomain
      proteins with metalloprotease, cell adhesion, and signaling activities. Human
      ADAM12, which is implicated in diseases such as cancer, is expressed in two
      splice forms, the transmembrane ADAM12-L and the shorter and soluble ADAM12-S.
      ADAM12 is synthesized as a zymogen with the prodomain keeping the metalloprotease
      inactive through a cysteine-switch mechanism. Maturation and activation of the
      protease involves the cleavage of the prodomain in the trans-Golgi or possibly at
      the cell surface by a furin-peptidase. The aim of the present study was to
      determine the fate of the prodomain following furin cleavage. Here we demonstrate
      that, following cleavage of the human ADAM12-S prodomain in the trans-Golgi by a
      furin-peptidase, the prodomain remains non-covalently associated with the mature
      molecule. Accordingly, both the 68-kDa mature form of ADAM12-S and the 25-kDa
      prodomain could be detected using domain-specific antisera in immunoprecipitation
      and Western blot analyses of human serum ADAM12 and purified recombinant human
      ADAM12. Using electron microscopy after negative staining we have furthermore
      obtained the first visualization of a full-length ADAM molecule, human ADAM12-S,
      and report that it appears to be a compact clover composed of four globular
      domains, one of which is the prodomain. Finally, our data demonstrate that the
      presence of the metalloprotease domain appears to be sufficient for the prodomain
      to remain associated with the mature ADAM12-S. Thus, we conclude that the
      prodomain of human ADAM12-S is an integral domain of the mature molecule and as
      such might have specific biological functions in the extracellular space.

PMID- 16455654
TI  - c-Met expression is regulated by Mitf in the melanocyte lineage.
AB  - Hepatocyte growth factor (HGF)/c-Met signaling is thought to be a key pathway in
      both melanocyte development and melanoma metastasis. Here, HGF stimulation of
      melanocytes was seen to up-regulate c-Met expression. In an effort to decipher
      the mechanism by which HGF up-regulates its receptor, we found that c-Met is a
      direct transcriptional target of Mitf. This was confirmed with chromatin
      immunoprecipitation experiments of the human c-Met promoter, as well as by the
      ability of adenovirally expressed Mitf to modulate endogenous c-Met protein
      levels in melanocytes. Disruption of Mitf blocked HGF-dependent increases in
      endogenous c-Met message and protein levels, indicating that HGF regulates its
      own receptor levels via Mitf. Finally, dominant-negative inhibition of Mitf
      resulted in profound resistance of melanocytes and melanoma cells to HGF
      dependent matrix invasion, suggesting a physiologic role for this pathway in
      melanocytic development and melanoma.

PMID- 16455655
TI  - Strict pairing of var promoters and introns is required for var gene silencing in
      the malaria parasite Plasmodium falciparum.
AB  - The human malaria parasite, Plasmodium falciparum, maintains a persistent
      infection altering the proteins expressed on the surface of the infected red
      blood cells, thus avoiding the host immune response. The primary surface antigen,
      a protein called PfEMP1, is encoded by a multicopy gene family called var. Each
      individual parasite only expresses a single var gene at a time, maintaining all
      other members of the family in a transcriptionally silent state. Previous work
      using reporter genes in transiently transfected plasmid constructs implicated a
      conserved intron found in all var genes in the silencing process. Here we have
      utilized episomal recombination within stably transformed parasites to generate
      different var promoter and intron arrangements and show that loss of the intron
      results in var promoter activation. Further, in multicopy plasmid concatamers,
      each intron could only silence a single promoter, suggesting a one-to-one pairing
      requirement for silencing. Transcriptionally active, "unpaired" promoters
      remained active after integration into a chromosome; however, they were not
      recognized by the pathway that maintains mutually exclusive var gene expression.
      The data indicate that intron/promoter pairing is responsible for silencing each
      individual var gene and that disruption of silencing of one gene does not affect
      the transcriptional activity of neighboring var promoters. This suggests that
      silencing is regulated at the level of individual genes rather than by assembly
      of silent chromatin throughout a chromosomal region, thus providing a possible
      explanation of how a var gene can be maintained in a silent state while the
      immediately adjacent var gene is transcriptionally active.

PMID- 16455656
TI  - CpSufE activates the cysteine desulfurase CpNifS for chloroplastic Fe-S cluster
      formation.
AB  - CpNifS, a cysteine desulfurase required to supply sulfur for ironsulfur cluster
      biogenesis in Arabidopsis thaliana chloroplasts, belongs to a class of NifS-like
      enzymes with low endogenous cysteine desulfurase activity. Its bacterial
      homologue SufS is stimulated by SufE. Here we characterize the Arabidopsis
      chloroplast protein CpSufE, which has an N-terminal SufE-like domain and a C
      terminal BolA-like domain unique to higher plants. CpSufE is targeted to the
      chloroplast stroma, indicated by green fluorescent protein localization and
      immunoblot experiments. Like CpNifS, CpSufE is expressed in all major tissues,
      with higher expression in green parts. Its expression is light-dependent and
      regulated at the mRNA level. The addition of purified recombinant CpSufE
      increased the Vmax for the cysteine desulfurase activity of CpNifS over 40-fold
      and decreased the KM toward cysteine from 0.1 to 0.043 mm. In contrast, CpSufE
      addition decreased the affinity of CpNifS for selenocysteine, as indicated by an
      increase in the KM from 2.9 to 4.17 mm, and decreased the Vmax for selenocysteine
      lyase activity by 30%. CpSufE forms dynamic complexes with CpNifS, indicated by
      gel filtration, native PAGE, and affinity chromatography experiments. A mutant of
      CpSufE in which the single cysteine was changed to serine was not active in
      stimulating CpNifS, although it did compete with WT CpSufE. The iron-sulfur
      cluster reconstitution activity of the CpNifS-CpSufE complex toward apoferredoxin
      was 20-fold higher than that of CpNifS alone. We conclude that CpNifS and CpSufE
      together form a cysteine desulfurase required for iron-sulfur cluster formation
      in chloroplasts.

PMID- 16455657
TI  - Conversion efficiency of bank vole prion protein in vitro is determined by
      residues 155 and 170, but does not correlate with the high susceptibility of bank
      voles to sheep scrapie in vivo.
AB  - The misfolded infectious isoform of the prion protein (PrP(Sc)) is thought to
      replicate in an autocatalytic manner by converting the cellular form (PrP(C))
      into its pathogenic folding variant. The similarity in the amino acid sequence of
      PrP(C) and PrP(Sc) influences the conversion efficiency and is considered as the
      major determinant for the species barrier. We performed in vitro conversion
      reactions on wild-type and mutated PrP(C) to determine the role of the primary
      sequence for the high susceptibility of bank voles to scrapie. Different
      conversion efficiencies obtained with bank vole and mouse PrP(C) in reactions
      with several prion strains were due to differences at amino acid residues 155 and
      170. However, the conversion efficiencies obtained with mouse and vole PrP(C) in
      reactions with sheep scrapie did not correlate with the susceptibility of the
      respective species to this prion strain. This discrepancy between in vitro and in
      vivo data may indicate that at least in the case of scrapie transmission to bank
      voles additional host factors can strongly modulate the species barrier.
      Furthermore, in vitro conversion reactions with different prion strains revealed
      that the degree of alteration of the conversion efficiency induced by amino acid
      exchanges was varying according to the prion strain. These results support the
      assumption that the repertoire of conformations adopted by a certain PrP(C)
      primary sequence is decisive for its convertibility to the strain-specific
      PrP(Sc) conformation.

PMID- 16455658
TI  - Laboratory-evolved vanadium chloroperoxidase exhibits 100-fold higher
      halogenating activity at alkaline pH: catalytic effects from first and second
      coordination sphere mutations.
AB  - Directed evolution was performed on vanadium chloroperoxidase from the fungus
      Curvularia inaequalis to increase its brominating activity at a mildly alkaline
      pH for industrial and synthetic applications and to further understand its
      mechanism. After successful expression of the enzyme in Escherichia coli, two
      rounds of screening and selection, saturation mutagenesis of a "hot spot," and
      rational recombination, a triple mutant (P395D/L241V/T343A) was obtained that
      showed a 100-fold increase in activity at pH 8 (k(cat) = 100 s(-1)). The
      increased K(m) values for Br(-) (3.1 mm) and H(2)O(2) (16 microm) are smaller
      than those found for vanadium bromoperoxidases that are reasonably active at this
      pH. In addition the brominating activity at pH 5 was increased by a factor of 6
      (k(cat) = 575 s(-1)), and the chlorinating activity at pH 5 was increased by a
      factor of 2 (k(cat) = 36 s(-1)), yielding the "best" vanadium haloperoxidase
      known thus far. The mutations are in the first and second coordination sphere of
      the vanadate cofactor, and the catalytic effects suggest that fine tuning of
      residues Lys-353 and Phe-397, along with addition of negative charge or removal
      of positive charge near one of the vanadate oxygens, is very important. Lys-353
      and Phe-397 were previously assigned to be essential in peroxide activation and
      halide binding. Analysis of the catalytic parameters of the mutant vanadium
      bromoperoxidase from the seaweed Ascophyllum nodosum also adds fuel to the
      discussion regarding factors governing the halide specificity of vanadium
      haloperoxidases. This study presents the first example of directed evolution of a
      vanadium enzyme.

PMID- 16455659
TI  - Functional genomic responses to cystic fibrosis transmembrane conductance
      regulator (CFTR) and CFTR(delta508) in the lung.
AB  - Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused
      by mutations in the cystic fibrosis transmembrane conductance regulator gene
      (CFTR) that disturbs fluid homeostasis and host defense in target organs. The
      effects of CFTR and delta508-CFTR were assessed in transgenic mice that 1) lack
      CFTR expression (Cftr-/-); 2) express the human delta508 CFTR (CFTR(delta508));
      3) overexpress the normal human CFTR (CFTR(tg)) in respiratory epithelial cells.
      Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to
      functional classification, k-means clustering, promoter cis-elements/modules
      searching, literature mining, and pathway exploring. Genomic responses to Cftr-/-
      were not corrected by expression of CFTR(delta508). Genes regulating host
      defense, inflammation, fluid and electrolyte transport were similarly altered in
      Cftr-/- and CFTR(delta508) mice. CFTR(delta508) induced a primary disturbance in
      expression of genes regulating redox and antioxidant systems. Genomic responses
      to CFTR(tg) were modest and were not associated with lung pathology. CFTR(tg) and
      CFTR(delta508) induced genes encoding heat shock proteins and other chaperones
      but did not activate the endoplasmic reticulum-associated degradation pathway.
      RNAs encoding proteins that directly interact with CFTR were identified in each
      of the CFTR mouse models, supporting the hypothesis that CFTR functions within a
      multiprotein complex whose members interact at the level of protein-protein
      interactions and gene expression. Promoters of genes influenced by CFTR shared
      common regulatory elements, suggesting that their co-expression may be mediated
      by shared regulatory mechanisms. Genes and pathways involved in the response to
      CFTR may be of interest as modifiers of CF.

PMID- 16455660
TI  - Parkin suppresses the expression of monoamine oxidases.
AB  - Mutations of parkin are linked to early onset Parkinson disease. Here we show
      that stable transfection of parkin in the human dopaminergic neuroblastoma cell
      line SH-SY5Y markedly reduced the activities of both monoamine oxidase (MAO) A
      and B. The amount of 3,4-dihydroxyphenylacetic acid, which is produced during
      dopamine oxidation by MAO, was greatly reduced by parkin overexpression.
      Radioligand binding assays showed that MAO binding sites were decreased
      accordingly. Consistent with these, MAO-B protein level was much lower, whereas
      the amount of MAO-A protein was not determined due to the lack of a suitable
      antibody. Co-transfection of either MAO with parkin in HEK293 cells did not
      significantly alter ubiquitination and degradation of each MAO. When we measured
      MAO expression by real-time quantitative reverse transcription-PCR, marked
      reductions were seen in SH-SY5Y cells stably expressing parkin compared with the
      parental cells or a control line stably transfected with luciferase. In addition,
      parkin mutants defective in E3 ligase activity exhibited different effects on MAO
      expression. We found that parkin also significantly decreased mRNA levels of both
      MAOs in the mouse fibroblast cell line NIH3T3. Furthermore, MAO expression was
      significantly increased in human B lymphocyte cell lines derived from Parkinson
      disease patients with homozygous but not heterozygous deletion of exon 4 of
      parkin. Together these results suggest that parkin suppresses MAO expression.
      This function may limit the production of reactive oxygen species generated by
      MAO in dopamine oxidation and would, thus, be beneficial to the survival of
      dopaminergic neurons.

PMID- 16455661
TI  - Persistent interleukin-1beta signaling causes long term activation of NFkappaB in
      a promoter-specific manner in human glial cells.
AB  - Nuclear factor-kappaB (NFkappaB) is an inducible transcription factor that plays
      a key role in regulating the expression of a wide range of immune and
      inflammatory response genes. The activity of NFkappaB is controlled at multiple
      levels, including cytoplasmic retention with inhibitor of kappaB (IkappaB)
      proteins in the basal state. Persistent activation of the transcription factor is
      seen in numerous chronic inflammatory disease states, and we have previously
      demonstrated sustained activation of NFkappaB in human glial cells upon
      stimulation with interleukin (IL)-1beta. In these cells, NFkappaB retains DNA
      binding activity for up to 72 h despite the presence of resynthesized
      IkappaBalpha and in the absence of IkappaBbeta. Here we characterized the
      apparent inability of newly synthesized IkappaBalpha to terminate activation of
      NFkappaB in glial cells. We showed unexpectedly that newly synthesized
      IkappaBalpha can enter the nucleus, interact with the NFkappaB subunit p65, and
      export it to the cytoplasm. However, in vitro analysis of enzyme activity
      demonstrates that IL-1beta causes the long term activation of the IkappaB kinase
      complex leading to chronic phosphorylation of the newly synthesized IkappaBalpha
      signal response domain and persistent activation of NFkappaB. Such sustained
      activation of NFkappaB is dependent on the continuous presence and activity of IL
      1beta. Interestingly, the sustained nature of NFkappaB activity is promoter type
      specific. Chromatin immunoprecipitation studies revealed that p65 is detected at
      the promoters of both intercellular adhesion molecule-1 and IL-8 1 h following IL
      1beta stimulation but is only found at the latter at 24 h. The functional
      significance of this finding is indicated by the transient induction of
      intercellular adhesion molecule-1 mRNA, but more sustained induction of IL-8
      expression, by IL-1beta. These studies thus demonstrated that persistent IL-1
      signaling causes sustained activation of NFkappaB in a promoter-specific manner
      in human glial cells, leading to prolonged induction of selective pro
      inflammatory genes. This is likely to make a key contribution to chronic
      inflammatory conditions of the brain.

PMID- 16455662
TI  - Acetylcholinesterase dynamics at the neuromuscular junction of live animals.
AB  - At cholinergic synapses, acetylcholinesterase (AChE) is critical for ensuring
      normal synaptic transmission. However, little is known about how this enzyme is
      maintained and regulated in vivo. In this work, we demonstrate that the
      dissociation of fluorescently-tagged fasciculin 2 (a specific and selective
      peptide inhibitor of AChE) from AChE is extremely slow. This fluorescent probe
      was used to study the removal and insertion of AChE at individual synapses of
      living adult mice. After a one-time blockade of AChEs with fluorescent fasciculin
      2, AChEs are removed from synapses initially at a faster rate (t(1/2) of
      approximately 3 days) and later at a slower rate (t(1/2) of approximately 12
      days). Most of the removed AChEs are replaced by newly inserted AChEs over time.
      However, when AChEs are continuously blocked with fasciculin 2, the removal rate
      increases substantially (t(1/2) of approximately 12 h), and most of the lost
      AChEs are not replaced by newly inserted AChE. Furthermore, complete one-time
      inactivation of AChE activity significantly increases the removal of postsynaptic
      nicotinic acetylcholine receptors (AChRs). Finally, time lapse imaging reveals
      that synaptic AChEs and AChRs that are removed from synapses are co-localized in
      the same pool after being internalized. These results demonstrate a remarkable
      AChE dynamism and argue for a potential link between AChE function and
      postsynaptic receptor lifetime.

PMID- 16455663
TI  - CDK-dependent activation of poly(ADP-ribose) polymerase member 10 (PARP10).
AB  - Proteins of the poly(ADP-ribose) polymerase (PARP) family play a wide array of
      functions, covering virtually every aspect of DNA metabolism and function, most
      notably with the response to DNA damage, transcription, and the maintenance of
      genomic stability. Here we report the identification and characterization of a
      novel PARP family member, PARP10 (FLJ14464 or hypothetical protein LOC84875).
      Overexpression of PARP10 results in loss of cell viability, although down
      expression by short hairpin RNA leads to delayed G1 progression and concomitant
      cell death. PARP10 exists in both cytoplasm and nucleus, but only nucleolar
      PARP10 acquires CDK-dependent phosphorylation through late-G1 to S phase, and
      from prometaphase to cytokinesis in the nucleolar organizing regions. The PARP
      activity of PARP10 depends on phosphorylation by CDK2-cyclin E in vitro. CDK
      phosphorylated PARP10 is absent in growth-arrested cells. These results suggest
      that PARP10 functions in cell proliferation and may serve as a marker for
      proliferating cells.

PMID- 16455664
TI  - Molecular models for murine sperm-egg binding.
AB  - Murine sperm initiate fertilization by binding to the specialized extracellular
      matrix of mouse eggs, known as the zona pellucida. Over the past decade, powerful
      genetic, biophysical, and biochemical techniques have been employed to gain new
      insights into this interaction. Evidence from these studies does not support
      either of two major models for binding first proposed over two decades ago. Two
      more recently established models suggest that protein-protein interactions
      predominate during this initial stage of fertilization. Another model proposes
      that about 75-80% of the murine sperm bound to zona pellucida under well defined
      in vitro conditions is carbohydrate dependent, with the remaining sperm bound via
      protein-protein interactions. Mounting evidence suggests that the carbohydrate
      sequences coating the murine egg could be employed as specific immune recognition
      markers. Continued investigation of this system may resolve many of these
      controversial findings and reveal novel functions for murine zona pellucida
      glycoproteins.

PMID- 16455665
TI  - A model for C74 addition by CCA-adding enzymes: C74 addition, like C75 and A76
      addition, does not involve tRNA translocation.
AB  - The CCA-adding enzyme adds CCA to the 3'-end of tRNA one nucleotide at a time,
      using CTP and ATP as substrates. We found previously that tRNA does not rotate or
      translocate on the enzyme during the addition of C75 and A76. We therefore
      predicted that the growing 3'-end of tRNA must, upon addition of each nucleotide,
      refold to reposition the new 3'-hydroxyl equivalently relative to the solitary
      nucleotidyltransferase motif. Cocrystal structures of the class I archaeal
      Archaeoglobus fulgidus enzyme, poised for addition of C75 and A76, confirmed this
      prediction. We have also demonstrated that an evolutionarily flexible beta-turn
      facilitates progressive refolding of the 3'-terminal C74 and C75 residues during
      C75 and A76 addition. Although useful cocrystals corresponding to C74 addition
      have not yet been obtained, we now show experimentally that tRNA does not rotate
      or translocate during C74 addition. We therefore propose, based on the existing
      A. fulgidus cocrystal structures, that the same flexible beta-turn functions as a
      wedge between the discriminator base (N73) and the terminal base pair of the
      acceptor stem, unstacking and repositioning N73 to attack the incoming CTP. Thus
      a single flexible beta-turn would orchestrate consecutive addition of all three
      nucleotides without significant movement of the tRNA on the enzyme surface.

PMID- 16455666
TI  - Structurally altered peptides reveal an important role for N-terminal heptad
      repeat binding and stability in the inhibitory action of HIV-1 peptide DP178.
AB  - Human immunodeficiency virus 1 gp41 folds into a six-helix bundle whereby three C
      terminal heptad repeat regions pack in an anti-parallel manner against the coiled
      coil formed by three N-terminal heptad repeats (NHR). Peptides that inhibit
      bundle formation contributed significantly to the understanding of the entry
      mechanism of the virus. DP178, which partially overlaps C-terminal heptad
      repeats, prevents bundle formation through an undefined mechanism; additionally
      it has been suggested to bind other ENV regions and arrest fusion in an unknown
      manner. We used two structurally altered DP178 peptides; in each, two sequential
      amino acids were substituted into their d configuration, d-SQ in the hydrophilic
      N-terminal region and d-LW in the hydrophobic C-terminal. Importantly, we
      generated an elongated NHR peptide, N54, obtaining the full N-helix docking site
      for DP178. Interestingly, d-LW retained wild type fusion inhibitory activity,
      whereas d-SQ exhibited significantly reduced activity. In correlation with the
      inhibitory data, CD spectroscopy and fluorescence studies revealed that all the
      DP178 peptides interact with N54, albeit with different stabilities of the
      bundles. We conclude that strong binding of DP178 N-terminal region to the
      endogenous NHR, without significant contribution of the C-terminal sequence of
      DP178 to core formation, is vital for DP178 inhibition. The finding that d-amino
      acid incorporation in the C terminus did not affect activity or membrane binding
      as revealed by surface plasmon resonance correlates with an additional membrane
      binding site, or membrane anchoring role, for the C terminus, which works
      synergistically with the N terminus to inhibit fusion.

PMID- 16455667
TI  - Binding of alpha-synuclein affects the lipid packing in bilayers of small
      vesicles.
AB  - The intracellular deposition of fibrillar aggregates of alpha-synuclein is a
      characteristic feature of Parkinson disease. Alternatively, as a result of its
      unusual conformational plasticity, alpha-synuclein may fold into an amphipathic
      helix upon contact with a lipid-water interface. Using spin label ESR and
      fluorescence spectroscopy, we show here that alpha-synuclein affects the lipid
      packing in small unilamellar vesicles. The ESR hyperfine splittings of spin
      labeled phospholipid probes revealed that alpha-synuclein induces chain ordering
      at carbon 14 of the acyl chains below the chain melting phase transition
      temperature but not in the liquid crystalline state of electroneutral vesicle
      membranes. Binding of alpha-synuclein leads to an increase in the temperature and
      cooperativity of the phase transition according to the fluorescence anisotropy of
      the hydrophobic polyene 1,6-diphenylhexatriene and of the fluorescence emission
      maxima of the amphiphilic probe 6-dodecanoyl-2-dimethylaminonaphthalene. Binding
      parameters were obtained from the fluorescence anisotropy measurements in
      combination with our previous determinations by titration calorimetry (Nuscher,
      B., Kamp, F., Mehnert, T., Odoy, S., Haass, C., Kahle, P. J., and Beyer, K.
      (2004) J. Biol. Chem. 279, 21966-21975). We also show that alpha-synuclein
      interacts with vesicle membranes containing sphingomyelin and cholesterol. We
      propose that the protein is capable of annealing defects in curved vesicle
      membranes, which may prevent synaptic vesicles from premature fusion.

PMID- 16455668
TI  - An unusual signal peptide extension inhibits the binding of bacterial
      presecretory proteins to the signal recognition particle, trigger factor, and the
      SecYEG complex.
AB  - Considerable evidence indicates that the Escherichia coli signal recognition
      particle (SRP) selectively targets proteins that contain highly hydrophobic
      signal peptides to the SecYEG complex cotranslationally. Presecretory proteins
      that contain only moderately hydrophobic signal peptides typically interact with
      trigger factor (TF) and are targeted post-translationally. Here we describe a
      striking exception to this rule that has emerged from the analysis of an unusual
      55-amino acid signal peptide associated with the E. coli autotransporter EspP.
      The EspP signal peptide consists of a C-terminal domain that resembles a
      classical signal peptide plus an N-terminal extension that is conserved in other
      autotransporter signal peptides. Although a previous study showed that proteins
      containing the C-terminal domain of the EspP signal peptide are targeted
      cotranslationally by SRP, we found that proteins containing the full-length
      signal peptide were targeted post-translationally via a novel TF-independent
      mechanism. Mutation of an invariant asparagine residue in the N-terminal
      extension, however, restored cotranslational targeting. Remarkably, proteins
      containing extremely hydrophobic derivatives of the EspP signal peptide were also
      targeted post-translationally. These and other results suggest that the N
      terminal extension alters the accessibility of the signal peptide to SRP and TF
      and promotes post-translational export by reducing the efficiency of the
      interaction between the signal peptide and the SecYEG complex. Based on data, we
      propose that the N-terminal extension mediates an interaction with an
      unidentified cytoplasmic factor or induces the formation of an unusual signal
      peptide conformation prior to the onset of protein translocation.

PMID- 16455669
TI  - Isolated ventricular non-compaction with restrictive cardiomyopathy.

PMID- 16455670
TI  - Interleukin-8 is associated with circulating CD133+ progenitor cells in acute
      myocardial infarction.
AB  - AIMS: Release of progenitor cells is observed during inflammatory conditions and
      contributes to neovascularization. We, therefore, sought to investigate the
      relationship of circulating progenitor cells and interleukin (IL)-8 in acute
      myocardial infarction (AMI). METHODS AND RESULTS: From patients with stable
      angina and AMI, serial venous blood samples were obtained. The number of
      circulating CD133+CD45- progenitor cells, endothelial progenitor cells (EPCs),
      and circulating endothelial P1H12+CD45- cells was analyzed by flow cytometry.
      After stenting in patients with AMI, an increase in plasma IL-8 and vascular
      endothelial growth factor (VEGF) concentrations was observed, which was only
      minimal in patients with stable angina. Only in patients with AMI, this was
      followed by an increase in circulating CD133+CD45- progenitor cells. In contrast,
      circulating endothelial P1H12+CD45- cells and E-selectin RNA expression in
      peripheral blood were only elevated early in AMI, indicating shedding of
      activated endothelial cells. Multivariable analysis revealed an association of IL
      8 and circulating CD133+CD45- progenitor cells in AMI, in addition to statin
      therapy and risk factor profile. CONCLUSION: In AMI, IL-8 is associated with
      circulating progenitor cells. In addition to the pro-angiogenic functions of IL-8
      and VEGF, this mechanism may contribute to new vessel generation and, thereby,
      improve myocardial function.

PMID- 16455671
TI  - Relapse and mortality following cardioversion of new-onset vs. recurrent atrial
      fibrillation and atrial flutter in the elderly.
AB  - AIMS: Trials of rate control vs. rhythm control for atrial fibrillation or
      flutter included few patients with new-onset arrhythmia. Our objective was to
      assess the relapse rate and the effect of the relapse of new-onset atrial
      arrhythmias on mortality after direct-current cardioversion (DCCV). METHODS AND
      RESULTS: A cohort of 351 patients with atrial fibrillation (new onset in 179) and
      126 patients with atrial flutter (new onset in 78) was followed-up after DCCV.
      Cox proportional hazard models were used. Median age was 74.6 years. Mean follow
      up for relapse was 7.7 months; for death, 29.4 months. Patients with new-onset
      atrial flutter [adjusted hazard ratio (HR) = 1] were more likely to maintain
      sinus rhythm than the patients with recurrent atrial flutter (adjusted HR = 2.5,
      P < 0.01), new-onset atrial fibrillation (adjusted HR = 2.4, P < 0.01), or
      recurrent atrial fibrillation (adjusted HR = 2.7, P < 0.01). Patients with new
      onset atrial fibrillation were as likely to have relapses as patients with
      recurrent atrial fibrillation or flutter. Relapse of atrial arrhythmia after DCCV
      was associated with increased mortality (adjusted HR= 3.1, P < 0.01). CONCLUSION:
      DCCV is more successful in maintaining sinus rhythm in patients with new-onset
      atrial flutter than in patients with new-onset atrial fibrillation. Relapse of
      atrial arrhythmia after cardioversion is associated with increased mortality.

PMID- 16455672
TI  - Obstructive intramural coronary amyloidosis: a distinct phenotype of cardiac
      amyloidosis that can cause acute heart failure.

PMID- 16455673
TI  - Prosthesis patient mismatch in aortic valve replacement: possible but pertinent?

PMID- 16455674
TI  - Withdrawal of therapy in patients with proliferative lupus nephritis: long-term
      follow-up.
AB  - BACKGROUND: Whether corticosteroid and immunosuppressive therapy may be safely
      withdrawn in patients with proliferative lupus nephritis is still unclear.
      METHODS: In 32 patients with biopsy-proven proliferative lupus nephritis
      previously put into remission, therapy was gradually tapered off. RESULTS: When
      immunosuppressive therapy was stopped (median: 38 months; 25th-75th percentile:
      24-81 months, after biopsy), 24 patients were in complete remission and eight had
      a median proteinuria of 1.05 g/24 h (25th-75th percentile: 0.91-1.1 g/24 h) with
      normal renal function. After stopping therapy, patients were followed for a
      median of 203 months (25th-75th percentile: 116-230 months). Fifteen patients
      (Group 1) never developed lupus activity. The other 17 patients (Group 2)
      developed lupus exacerbations in a median of 34 months (25th-75th percentile: 29
      52 months) after stopping therapy and were re-treated. The only significant
      differences between the two groups were the longer median durations of treatment,
      57 months (25th-75th percentile: 41.5-113.5 months) vs 30 months (25th-75th
      percentile: 18-41 months; P<0.009), and remission, 24 months (25th-75th
      percentile: 18-41) vs 12 months (25th-75th percentile: 7-20 months; P<0.02),
      before stopping therapy in Group 1 than in Group 2. At last follow-up, 12
      patients of Group 1 were in complete remission, two had mild proteinuria and one
      had died. In Group 2, one patient died, 14 were in complete remission, one had
      mild proteinuria and in another patient serum creatinine doubled. CONCLUSIONS:
      Some patients with severe lupus nephritis who enter stable remission can be
      maintained without any specific treatment for many years. Those patients who have
      new flares can again go into remission with an appropriate treatment. The longer
      the treatment and remission before withdrawal, the lower the risk of relapse.

PMID- 16455675
TI  - Acute granulomatous tubulointerstitial nephritis caused by intravesical BCG.

PMID- 16455676
TI  - Vitamin D decreases NFkappaB activity by increasing IkappaBalpha levels.
AB  - BACKGROUND: In a previous study we demonstrated the inhibitory effect of 1,25
      dihydroxyvitamin D (1,25(OH)(2)D(3)) and its less calcaemic analog
      1,24(OH)(2)D(2) on the production of tumour necrosis factor alpha (TNFalpha) by
      human peritoneal macrophages. The aim of the present study is to examine whether
      this vitamin D inhibition of TNFalpha is mediated by its major transcription
      factor, nuclear factor-kappaB (NFkappaB). METHODS: Murine macrophage cells
      (P388D1) were incubated with 10(-7) M 1,25(OH)(2)D(3) or 1,24(OH)(2)D(2) and then
      stimulated with lipopolysaccharide. NFkappaB activity was assayed using a
      reporter gene and by electrophoretic mobility shift assay (EMSA). In addition, we
      evaluated mRNA and protein levels of NFkappaB-p65 and of IkappaBalpha, a potent
      NFkappaB inhibitor, and phosphorylated IkappaBalpha. RESULTS: Both
      1,25(OH)(2)D(3) and 1,24(OH)(2)D(2) induced a 60% reduction of TNFalpha
      secretion. By using a reporter gene and EMSA we found that vitamin D markedly
      reduced NFkappaB activity. 1,25(OH)(2)D(3) or 1,24(OH)(2)D(2) decreased NFkappaB
      p65 levels in the nucleus and increased NFkappaB-p65 levels in the cytosol; no
      changes were observed in the total levels of NFkappaB-p65 protein and mRNA.
      Concurrently, vitamin D induced a significant increase in mRNA and protein levels
      of IkappaBalpha (approximately 6.5- and 4.5-fold, respectively). Elevated levels
      of IkappaBalpha can be explained by the vitamin D-induced prolongation of
      IkappaBalpha-mRNA half-life from 110 to 190 min and by the decrease in
      IkappaBalpha phosphorylation. CONCLUSIONS: Vitamin D up-regulates IkappaBalpha
      levels by increasing mRNA stability and decreasing IkappaBalpha phosphorylation.
      The increase in IkappaBalpha levels reduces nuclear translocation of NFkappaB and
      thereby downgrades its activity. Since NFkappaB is a major transcription factor
      of inflammatory mediators, these findings suggest that the less-calcaemic analog,
      1,24(OH)(2)D(2) may be effective as an anti-inflammatory therapeutic agent.

PMID- 16455677
TI  - Weekly short infusion of taxotere at a 4 week cycle in Chinese patients with
      advanced NSCLC who have failed or relapsed after the frontline platinum-based non
      taxane chemotherapy--a Phase II trial.
AB  - BACKGROUND: This Phase II study was conducted to evaluate the efficacy and
      toxicity of weekly docetaxel at a 4 week cycle in second-line therapy for
      patients with advanced non-small cell lung cancer (NSCLC) who failed to respond
      or relapsed after the frontline platinum-based, non-taxane regimen. METHODS:
      Patients with histologically confirmed and progressive NSCLC after one platinum
      based, non-taxane regimen were eligible for this study. Performance status of 0-2
      and adequate organ function were required. Patients were treated with docetaxel
      40 mg/m(2)/week for three consecutive weeks then following 1 week of rest. Cycles
      were repeated every 4 weeks for a maximum total of six cycles. Docetaxel was
      administered intravenously for 30 min with dexamethasone premedication. RESULTS:
      Fifty-three patients were eligible for this study. Hematologic toxicity was very
      mild and with the major toxicity of anemia. Non-hematologic toxicities were
      modest, Grades 3-4 mucositis, diarrhea and peripheral neuropathy occurred in 6
      13% of patients and caused dose modifications. Fatigue (48%) was common but not
      severe with only 6% of Grades 3-4 toxicity. The overall response rate (ORR) was
      13% [95% confidence interval (CI), 3.9-23%]. The median survival time (MST) for
      all patients was 25.0 weeks (95% CI, 12.7-37.3), and the 1 year survival was 31%
      (95% CI, 17-58%). For patients with PS 0-1, MST was 29.7 weeks and 1 year
      survival was 36%. CONCLUSIONS: Weekly docetaxel appeared to be well tolerated as
      second-line therapy for patients with NSCLC. The efficacy for this regimen was
      comparable with the standard 3 week schedule but hematologic toxicity was
      markedly reduced. A schedule of three consecutive weeks, with a 1 week break, may
      diminish the frequency of fatigue and diarrhea when compared with a schedule of
      six consecutive weeks.

PMID- 16455678
TI  - A case of mucinous cystic tumor of the pancreatic tail.

PMID- 16455679
TI  - International comparisons of cumulative risk of all-site cancer, from cancer
      incidence in five continents vol. VIII.

PMID- 16455680
TI  - Physical and genetic interactions link hox function with diverse transcription
      factors and cell signaling proteins.
AB  - Positional information provided by Hox homeotic transcription factors is
      integrated with other transcription factors and cell signaling cascades in
      specific combinations to dictate context- and gene-specific Hox activity. Protein
      protein interactions between these groups have long been hypothesized to modulate
      Hox functions, yielding a context-specific function. However, difficulties in
      applying interaction screens to potent transcription factors have limited partner
      identification. A yeast two-hybrid screen using transcription activation
      deficient mutants of the Drosophila melanogaster Hox protein Ultrabithorax IB
      identified an array of interacting proteins, consisting primarily of
      transcription factors and components of cell signaling pathways. Interactions
      were confirmed with wild-type Ultrabithorax (UBX) in phage display experiments
      and by immunoprecipitation for a subset of partners. In vivo assays demonstrated
      that two Ultrabithorax IB partners, Armadillo, regulated by Wingless/WNT
      signaling, and the homeodomain protein Aristaless, inhibit UBX-dependent haltere
      development from the default wing development pathway. Therefore, transcription
      factors and cell signaling proteins that subdivide Hox-specified tissues can both
      alter Hox function in vivo and interact with the corresponding Hox protein in
      vitro. UBX may also modulate partner function: the pupal death phenotype induced
      by ectopic expression of the UBX partner Hairy required the presence of UBX.
      Thus, Hox.transcription factor complexes may integrate a variety of positional
      cues, generating the specificity and versatility required for context-dependent
      Hox function.

PMID- 16455681
TI  - Proteome analysis of an aerobic hyperthermophilic crenarchaeon, Aeropyrum pernix
      K1.
AB  - We analyzed the proteome of a crenararchaeon, Aeropyrum pernix K1, by using the
      following four methods: (i) two-dimensional PAGE followed by MALDI-TOF MS, (ii)
      one-dimensional SDS-PAGE in combination with two-dimensional LC-MS/MS, (iii)
      multidimensional LC-MS/MS, and (iv) two-dimensional PAGE followed by amino
      terminal amino acid sequencing. These methods were found to be complementary to
      each other, and biases in the data obtained in one method could largely be
      compensated by the data obtained in the other methods. Consequently a total of
      704 proteins were successfully identified, 134 of which were unique to A. pernix
      K1, and 19 were not described previously in the genomic annotation. We found that
      the original annotation of the genomic data of this archaeon was not adequate in
      particular with respect to proteins of 10-20 kDa in size, many of which were
      described as hypothetical. Furthermore the amino-terminal amino acid sequence
      analysis indicated that surprisingly the translation of 52% of their genes starts
      with TTG in contrast to ATG (28%) and GTG (20%). Thus, A. pernix K1 is the first
      example of an organism in which TTG is the most predominant translational
      initiation codon.

PMID- 16455682
TI  - Are rate constants constant?

PMID- 16455683
TI  - Recent observations on the regulation of fetal metabolism by glucose.
AB  - Glucose is the principal energy substrate for the the fetus and is essential for
      normal fetal metabolism and growth. Fetal glucose metabolism is directly
      dependent on the fetal plasma glucose concentration. Fetal glucose utilization is
      augmented by insulin produced by the developing fetal pancreas in increasing
      amounts as gestation proceeds, which enhances glucose utilization among the
      insulin-sensitive tissues (skeletal muscle, liver, heart, adipose tissue) that
      increase in mass and thus glucose need during late gestation. Glucose-stimulated
      insulin secretion increases over gestation. Both insulin secretion and insulin
      action are affected by prevailing glucose concentrations and the amount and
      activity of tissue glucose transporters. In cases of intrauterine growth
      restriction (IUGR), fetal weight-specific tissue glucose uptake rates and glucose
      transporters are maintained or increased, while synthesis of amino acids into
      protein and corresponding insulin-IGF signal transduction proteins are decreased.
      These observations demonstrate the mixed phenotype of the IUGR fetus that
      includes enhanced glucose utilization capacity, but diminished protein synthesis
      and growth. Thus, the fetus has considerable capacity to adapt to changes in
      glucose supply by relatively common and understandable mechanisms that regulate
      fetal metabolism and growth and could underlie certain later life metabolic
      disorders such as insulin resistance, obesity and diabetes mellitus.

PMID- 16455684
TI  - Fetal programming of autonomic and HPA function: do people who were small babies
      have enhanced stress responses?
AB  - Studies in several species have demonstrated that an adverse early environment
      can influence the development of the autonomic nervous system and hypothalamic
      pituitary-adrenal (HPA) axis. The autonomic nervous system and HPA axis are key
      components of the neuroendocrine response to stress and many of these animal
      models show altered biological responses to stress. Recent research now suggests
      that these processes operate in humans. An adverse early environment, as
      evidenced by reduced birth or infant weight, is associated with enhanced
      autonomic and HPA responses to experimental psychological stress. However, there
      appear to be marked sex differences in the mechanisms involved. Epidemiological
      studies demonstrate that physiological changes in these neuroendocrine systems
      may predispose to cardiovascular disease through their influence on risk factors
      such as plasma glucose and lipid concentrations and blood pressure. Thus the
      combination of enhanced stress susceptibility and the psychosocial stressors to
      which people are exposed may be an important component of the disease risk in
      human populations.

PMID- 16455685
TI  - Limited oxygen diffusion accelerates fatigue development in mouse skeletal
      muscle.
AB  - Isolated whole skeletal muscles fatigue more rapidly than isolated single muscle
      fibres. We have now employed this difference to study mechanisms of skeletal
      muscle fatigue. Isolated whole soleus and extensor digitorum longus (EDL) muscles
      were fatigued by repeated tetanic stimulation while measuring force production.
      Neither application of 10 mm lactic acid nor increasing the [K(+)] of the bath
      solution from 5 to 10 mm had any significant effect on the rate of force decline
      during fatigue induced by repeated brief tetani. Soleus muscles fatigued slightly
      faster during continuous tetanic stimulation in 10 mm[K(+)]. Inhibition of
      mitochondrial respiration with cyanide resulted in a faster fatigue development
      in both soleus and EDL muscles. Single soleus muscle fibres were fatigued by
      repeated tetani while measuring force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)).
      Under control conditions, the single fibres were substantially more fatigue
      resistant than the whole soleus muscles; tetanic force at the end of a series of
      100 tetani was reduced by about 10% and 50%, respectively. However, in the
      presence of cyanide, fatigue developed at a similar rate in whole muscles and
      single fibres, and tetanic force at the end of fatiguing stimulation was reduced
      by approximately 80%. The force decrease in the presence of cyanide was
      associated with a approximately 50% decrease in tetanic [Ca(2+)](i), compared
      with an increase of approximately 20% without cyanide. In conclusion, lactic acid
      or [K(+)] has little impact on fatigue induced by repeated tetani, whereas
      hypoxia speeds up fatigue development and this is mainly due to an impaired
      Ca(2+) release from the sarcoplasmic reticulum.

PMID- 16455686
TI  - Bidirectional modulation of GABAergic transmission by cholecystokinin in
      hippocampal dentate gyrus granule cells of juvenile rats.
AB  - Cholecystokinin (CCK) interacts with two types of G protein-coupled receptors in
      the brain: CCK-A and CCK-B receptors. Both CCK and CCK-B receptors are widely
      distributed in the hippocampal formation, but the functions of CCK there have
      been poorly understood. In the present study, we initially examined the effects
      of CCK on GABA(A) receptor-mediated synaptic transmission in the hippocampal
      formation and then explored the underlying cellular mechanisms by focusing on the
      dentate gyrus region, where the highest levels of CCK-binding sites have been
      detected. Our results indicate that activation of CCK-B receptors initially and
      transiently increased spontaneous IPSC (sIPSC) frequency, followed by a
      persistent reduction. The effects of CCK were more evident in juvenile rats,
      suggesting that they are developmentally regulated. Cholecystokinin failed to
      modulate the miniature IPSCs recorded in the presence of TTX and the amplitude of
      the evoked IPSCs, but produced a transient increase followed by a reduction in
      action potential firing frequency recorded from GABAergic interneurons,
      suggesting that CCK acts by modulating the excitability of the interneurons to
      regulate GABA release. Cholecystokinin reduced the amplitude of the after
      hyperpolarization of the action potentials, and application of paxilline or
      charybdotoxin considerably reduced CCK-mediated modulation of sIPSC frequency,
      suggesting that the effects of CCK are related to the inhibition of Ca(2+)
      activated K(+) currents (I(K(Ca))). The effects of CCK were independent of the
      functions of phospholipase C, intracellular Ca(2+) release, protein kinase C or
      phospholipase A(2), suggesting a direct coupling between the G proteins of CCK-B
      receptors and I(K(Ca)). Our results provide a novel mechanism underlying CCK
      mediated modulation of GABA release.

PMID- 16455687
TI  - Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2-sensitive
      neurons in rats.
AB  - The rat retrotrapezoid nucleus (RTN) contains pH-sensitive neurons that are
      putative central chemoreceptors. Here, we examined whether these neurons respond
      to peripheral chemoreceptor stimulation and whether the input is direct from the
      solitary tract nucleus (NTS) or indirect via the respiratory network. A dense
      neuronal projection from commissural NTS (commNTS) to RTN was revealed using the
      anterograde tracer biotinylated dextran amine (BDA). Within RTN, 51% of BDA
      labelled axonal varicosities contained detectable levels of vesicular glutamate
      transporter-2 (VGLUT2) but only 5% contained glutamic acid decarboxylase-67
      (GAD67). Awake rats were exposed to hypoxia (n = 6) or normoxia (n = 5) 1 week
      after injection of the retrograde tracer cholera toxin B (CTB) into RTN. Hypoxia
      activated neurons were identified by the presence of Fos-immunoreactive nuclei.
      CommNTS neurons immunoreactive for both Fos and CTB were found only in hypoxia
      treated rats. VGLUT2 mRNA was detected in 92 +/- 13% of these neurons whereas
      only 12 +/- 9% contained GAD67 mRNA. In urethane-chloralose-anaesthetized rats,
      bilateral inhibition of the RTN with muscimol eliminated the phrenic nerve
      discharge (PND) at rest, during hyperoxic hypercapnia (10% CO(2)), and during
      peripheral chemoreceptor stimulation (hypoxia and/or i.v. sodium cyanide, NaCN).
      RTN CO(2)-activated neurons were recorded extracellularly in anaesthetized intact
      or vagotomized rats. These neurons were strongly activated by hypoxia (10-15%
      O(2); 30 s) or by NaCN. Hypoxia and NaCN were ineffective in rats with carotid
      chemoreceptor denervation. Bilateral injection of muscimol into the ventral
      respiratory column 1.5 mm caudal to RTN eliminated PND and the respiratory
      modulation of RTN neurons. Muscimol did not change the threshold and sensitivity
      of RTN neurons to hyperoxic hypercapnia nor their activation by peripheral
      chemoreceptor stimulation. In conclusion, RTN neurons respond to brain P(CO(2))
      presumably via their intrinsic chemosensitivity and to carotid chemoreceptor
      activation via a direct glutamatergic pathway from commNTS that bypasses the
      respiratory network. RTN neurons probably contribute a portion of the chemical
      drive to breathe.

PMID- 16455688
TI  - Convergence of multiple pelvic organ inputs in the rat rostral medulla.
AB  - Electrophysiological recordings were used to investigate the degree of
      pelvic/visceral convergent inputs onto single medullary reticular formation (MRF)
      neurons. A total of 94 MRF neurons responsive to bilateral electrical stimulation
      of the pelvic nerve (PN) in 12 urethane-anaesthetized male rats were tested for
      responses to mechanical stimulation of the urinary bladder, urethra, colon and
      penis, and electrical stimulation of the dorsal nerve of the penis (DNP) and
      abdominal branches of the vagus. Responses to distension of the bladder were
      found for 51% (n = 48) of the MRF neurons tested. Of these 48, 71% responded to
      urethral infusion, 81% responded to colon distension, 100% responded to penile
      stimulation (and DNP), and 85% responded to vagal stimulation, with 62%
      responding to stimulation of all four of these territories. This high degree of
      visceral convergence (i.e. 62%) in a subset of PN-responsive MRF neurons is
      significantly greater than for the subset of PN-responsive MRF neurons that did
      not respond to urinary bladder distension (i.e. out of the 46 remaining neurons,
      none responded to all four of the other pelvic/visceral stimuli combined). These
      results suggest that the neurons processing information from the urinary bladder
      at this level of the neural axis are likely to be important for mediating
      interactions between different visceral organs for the coordination of multiple
      pelvic/visceral functions.

PMID- 16455689
TI  - Extracellular guanosine-5'-triphosphate modulates myogenesis via intermediate
      Ca(2+)-activated K+ currents in C2C12 mouse cells.
AB  - In this study we investigated the role of extracellular 5'-guanosine-triphosphate
      (GTP) on early phases of skeletal muscle differentiation using the widely used
      C2C12 mouse cells as a myogenic model. We show that extracellular GTP binding to
      specific sites activates a metabotropic cascade that leads to a transient
      intracellular Ca2+ mobilization, consequent activation of the intermediate Ca(2+)
      activated K+ channels (IK(Ca)), and hyperpolarization of the plasma membrane. We
      further show that in differentiating C2C12 myoblasts GTP induces a proliferative
      boost, and increases the number of cells positive for the myosin heavy chain
      (MyHC) proteins. These effects were shown to be mediated by the IK(Ca) channel
      dependent hyperpolarization, as evidenced by their disappearance when myoblasts
      were incubated with the IK(Ca) channel inhibitor charybdotoxin. These data give
      new insights into nucleotide purinergic signalling pathways, and address the role
      of the GTP-dependent IK(Ca) channel activation and hyperpolarization in
      myogenesis.

PMID- 16455690
TI  - Ca2+ controls slow NAD(P)H oscillations in glucose-stimulated mouse pancreatic
      islets.
AB  - Exposure of pancreatic islets of Langerhans to physiological concentrations of
      glucose leads to secretion of insulin in an oscillatory pattern. The oscillations
      in insulin secretion are associated with oscillations in cytosolic Ca(2+)
      concentration ([Ca(2+)](c)). Evidence suggests that the oscillations in
      [Ca(2+)](c) and secretion are driven by oscillations in metabolism, but it is
      unclear whether metabolic oscillations are intrinsic to metabolism or require
      Ca(2+) feedback. To address this question we explored the interaction of Ca(2+)
      concentration and islet metabolism using simultaneous recordings of NAD(P)H
      autofluorescence and [Ca(2+)](c), in parallel with measurements of mitochondrial
      membrane potential (DeltaPsi(m)). All three parameters responded to 10 mm glucose
      with multiphasic dynamics culminating in slow oscillations with a period of
      approximately 5 min. This was observed in approximately 90% of islets examined
      from various mouse strains. NAD(P)H oscillations preceded those of [Ca(2+)](c),
      but their upstroke was often accelerated during the increase in [Ca(2+)](c), and
      Ca(2+) influx was a prerequisite for their generation. Prolonged elevations of
      [Ca(2+)](c) augmented NAD(P)H autofluorescence of islets in the presence of 3 mm
      glucose, but often lowered NAD(P)H autofluorescence of islets exposed to 10 mm
      glucose. Comparable rises in [Ca(2+)](c) depolarized DeltaPsi(m). The NAD(P)H
      lowering effect of an elevation of [Ca(2+)](c) was reversed during inhibition of
      mitochondrial electron transport. These findings reveal the existence of slow
      oscillations in NAD(P)H autofluorescence in intact pancreatic islets, and suggest
      that they are shaped by Ca(2+) concentration in a dynamic balance between
      activation of NADH-generating mitochondrial dehydrogenases and a Ca(2+)-induced
      decrease in NADH. We propose that a component of the latter reflects
      mitochondrial depolarization by Ca(2+), which reduces respiratory control and
      consequently accelerates oxidation of NADH.

PMID- 16455691
TI  - Requirements for a high rate of potassium excretion in rats consuming a low
      electrolyte diet.
AB  - Control mechanisms for potassium (K(+)) excretion in humans developed in
      Palaeolithic times when diets were sodium poor and episodically K(+) rich.
      Nevertheless, our understanding of the regulation of K(+) excretion comes from
      experiments in rats with large sodium and K(+) intakes. Our objective was to
      identify how K(+) excretion was regulated when rats consumed a low NaCl diet to
      reflect Palaeolithic conditions. Rats that were given mineralocorticoids plus
      either NaCl, mannitol, or NaHCO(3) had a small kaliuresis. In contrast, KCl load
      induced a large kaliuresis and a near-maximal luminal [K(+)] in the terminal
      cortical collecting duct ([K(+)](CCD)). The time course of events was important.
      The rise in the [K(+)](CCD) was prompt, but the initial kaliuresis was only
      modest. Over the next 4 h, kaliuresis increased markedly due solely to a higher
      calculated distal flow rate, which appeared to be due to diminished reabsorption
      of NaCl in the loop of Henle; of note, the measured papillary [K(+)] rose. In
      summary, the increase in the [K(+)](CCD) in rats given KCl is likely to be due to
      an increase in the number of luminal K(+) channels rather than to mechanisms that
      are known to induce a lumen-negative voltage in cortical distal nephron segments.
      The higher distal flow rate might be due to a higher interstitial [K(+)], which
      inhibited NaCl reabsorption in the loop of Henle. Thus, to understand which of
      the potential control mechanisms are operating, one must look very closely at the
      conditions imposed by the experimental setting.

PMID- 16455692
TI  - Glutamate uptake block triggers deadly rhythmic bursting of neonatal rat
      hypoglossal motoneurons.
AB  - In the brain the extracellular concentration of glutamate is controlled by glial
      transporters that restrict the neurotransmitter action to synaptic sites and
      avoid excitotoxicity. Impaired transport of glutamate occurs in many cases of
      amyotrophic lateral sclerosis, a devastating motoneuron disease. Motoneurons of
      the brainstem nucleus hypoglossus are among the most vulnerable, giving early
      symptoms like slurred speech and dysphagia. However, the direct consequences of
      extracellular glutamate build-up, due to uptake block, on synaptic transmission
      and survival of hypoglossal motoneurons remain unclear and have been studied
      using the neonatal rat brainstem slice preparation as a model. Patch clamp
      recording from hypoglossal motoneurons showed that, in about one-third of these
      cells, inhibition of glutamate transport with the selective blocker dl-threo-beta
      benzyloxyaspartate (TBOA; 50 mum) unexpectedly led to the emergence of rhythmic
      bursting consisting of inward currents of long duration with superimposed fast
      oscillations and synaptic events. Synaptic inhibition block facilitated bursting.
      Bursts had a reversal potential near 0 mV, and were blocked by tetrodotoxin, the
      gap junction blocker carbenoxolone, or antagonists of AMPA, NMDA or mGluR1
      glutamate receptors. Intracellular Ca(2+) imaging showed bursts as synchronous
      discharges among motoneurons. Synergy of activation of distinct classes of
      glutamate receptor plus gap junctions were therefore essential for bursting.
      Ablating the lateral reticular formation preserved bursting, suggesting
      independence from propagated network activity within the brainstem. TBOA
      significantly increased the number of dead motoneurons, an effect prevented by
      the same agents that suppressed bursting. Bursting thus represents a novel
      hallmark of motoneuron dysfunction triggered by glutamate uptake block.

PMID- 16455694
TI  - Recommended relative potency factors for 2,3,4,7,8-pentachlorodibenzofuran: the
      impact of different dose metrics.
AB  - The recent National Toxicology Program (NTP) cancer bioassays for 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4
      PeCDF) permit a reevaluation of the current TEF value of 4-PeCDF. The data also
      allow for the derivation of relative potency factors (RPFs) for cancer, which are
      based not only on administered dose but also on potentially more informative dose
      metrics, such as liver concentration, area under the liver concentration curve,
      and lifetime average body burden. Our analyses of these data indicate that chi
      squared tests of observed versus predicted liver tumor incidence for 4-PeCDF
      reject the current TEF value of 0.5 value as too high. 4-PeCDF RPFs were derived
      using estimation methods that either did or did not assume parallelism of the 4
      PeCDF and TCDD dose-response curves. The resulting parallelism-based RPFs for
      administered dose, liver concentration at terminal sacrifice, liver concentration
      AUC, and lifetime average body burden are 0.26, 0.014, 0.021, and 0.036,
      respectively. The administered dose RPF estimate is approximately one-half the
      current TEF value of 0.5. However, the use of administered dose fails to take
      into account pharmacokinetic differences between congeners and the generally
      acknowledged belief that body burden or some other measure of cumulative dose is
      more appropriate for estimating the health risk posed by persistent chemicals.
      The other three dose metrics do account for these important factors, and the
      corresponding RPFs are at least 10-fold lower than the current TEF for 4-PeCDF.
      In summary, our analyses support an administered dose TEF no greater than 0.25
      and one in the 0.05-0.1 range for internal dose metrics such as lifetime average
      liver concentration or body burden.

PMID- 16455693
TI  - Modes and models of GABA(A) receptor gating.
AB  - Upon activation by agonist, the type A gamma-aminobutyric acid receptor (GABAR)
      'gates', allowing chloride ions to permeate membranes and produce fast inhibition
      of neurons. There is no consensus kinetic model for the GABAR gating mechanism.
      We expressed human alpha(1)beta(1)gamma(2S) GABARs in HEK 293 cells and recorded
      single channel currents in the cell-attached configuration using various GABA
      concentrations (50-5000 microm). Closed and open events occurred individually and
      in clusters that had at least three different modes that were distinguishable by
      open probability (P(O)): High (P(O)= 0.73), Mid (P(O)= 0.50), and Low (P(O)=
      0.21). We used a critical time to isolate shorter bursts of openings and to thus
      eliminate long-lived, desensitized events. Bursts from all three modes contained
      three closed and three open components. We employed maximum likelihood fitting,
      autocorrelation analysis and macroscopic current simulation to distinguish
      kinetic schemes. The 'core' gating scheme for most models contained two closed
      states that preceded an open state (C(1) C(2) O(1)). The two best-fitting models
      had a third closed state connected to C(1) and a second open state (O(2))
      connected to C(2). The third open state, whose occupancy varied greatly between
      modes, could be connected either to O(2) or C(2). We estimated rate constants for
      two identical, independent GABA binding steps by globally fitting data across
      GABA concentrations ranging from 50 to 1000 microm. For the most highly ranked
      model the binding rate constants were: k(+)= 3 microm(-1) s(-1) and k(-)= 272 s(
      1) (K(D)= 91 microm).

PMID- 16455695
TI  - Oral misoprostol for induction of labour at term: randomised controlled trial.
AB  - OBJECTIVE: To compare oral misoprostol solution with vaginal prostaglandin gel
      (dinoprostone) for induction of labour at term to determine whether misoprostol
      is superior. DESIGN: Randomised double blind placebo controlled trial. SETTING:
      Maternity departments in three hospitals in Australia. Population Pregnant women
      with a singleton cephalic presentation at > or = 36+6 weeks' gestation, with an
      indication for prostaglandin induction of labour. INTERVENTIONS: 20 mug oral
      misoprostol solution at ourly intervals and placebo vaginal gel or vaginal
      dinoprostone gel at six hourly intervals and placebo oral solution. MAIN OUTCOME
      MEASURES: Vaginal birth within 24 hours; uterine hyperstimulation with associated
      changes in fetal heart rate; caesarean section (all); and caesarean section for
      fetal distress. RESULTS: 741 women were randomised, 365 to the misoprostol group
      and 376 to the vaginal dinoprostone group. There were no significant differences
      between the two treatment groups in the primary outcomes: vaginal birth not
      achieved in 24 hours (misoprostol 168/365 (46.0%) v dinoprostone 155/376 (41.2%);
      relative risk 1.12, 95% confidence interval 0.95 to 1.32; P = 0.134), caesarean
      section (83/365 (22.7%) v 100/376 (26.6%); 0.82, 0.64 to 1.06; P = 0.127),
      caesarean section for fetal distress (32/365 (8.8%) v 35/376 (9.3%); 0.91, 0.57
      to 1.44; P = 0.679), or uterine hyperstimulation with changes in fetal heart rate
      (3/365 (0.8%) v 6/376 (1.6%); 0.55, 0.14 to 2.21; P = 0.401). Although there were
      differences in the process of labour induction, there were no significant
      differences in adverse maternal or neonatal outcomes. CONCLUSIONS: This trial
      shows no evidence that oral misoprostol is superior to vaginal dinoprostone for
      induction of labour. However, it does not lead to poorer health outcomes for
      women or their infants, and oral treatment is preferred by women. TRIAL
      REGISTRATION: National Health and Medical Research Council, Perinatal Trials,
      PT0361.

PMID- 16455696
TI  - Best research.

PMID- 16455697
TI  - Antibiotics in pandemic flu.

PMID- 16455698
TI  - Collaborative care for depression.

PMID- 16455699
TI  - The incidence of gastroschisis.

PMID- 16455700
TI  - Detention of refugees.

PMID- 16455703
TI  - Babies born after preimplantation genetic diagnosis need follow-up.

PMID- 16455704
TI  - NEJM editor gives pretrial evidence in Vioxx case.

PMID- 16455707
TI  - Police question former GP about assisted suicide.

PMID- 16455708
TI  - Serious birth defects kill at least three million children a year.

PMID- 16455711
TI  - Doctors in India prosecuted for sex determination, but few convicted.

PMID- 16455715
TI  - Reporter who accused surgeon of experimentation told to reveal sources.

PMID- 16455716
TI  - China's HIV/AIDS epidemic is sharply on the rise.

PMID- 16455721
TI  - Use of personal child health records in the UK: findings from the millennium
      cohort study.
AB  - OBJECTIVES: The personal child health record (PCHR) is a record of a child's
      growth, development, and uptake of preventive health services, designed to
      enhance communication between parents and health professionals. We examined its
      use throughout the United Kingdom with respect to recording children's weight and
      measures of social disadvantage and infant health. DESIGN: Cross sectional survey
      within a cohort study. SETTING: UK. PARTICIPANTS: Mothers of 18,503 children born
      between 2000 and 2002, living in the UK at 9 months of age. MAIN OUTCOME
      MEASURES: Proportion of mothers able to produce their child's PCHR; proportion of
      PCHRs consulted containing record of child's last weight; effective use of the
      PCHR (defined as production, consultation, and child's last weight recorded).
      RESULTS: In all, 16,917 (93%) mothers produced their child's PCHR and 15,138
      (85%) mothers showed effective use of their child's PCHR. Last weight was
      recorded in 97% of PCHRs consulted. Effective use was less in children previously
      admitted to hospital, and, in association with factors reflecting social
      disadvantage, including residence in disadvantaged communities, young maternal
      age, large family size (four or more children; incidence rate ratio 0.87; 95%
      confidence interval 0.83 to 0.91), and lone parent status (0.88; 0.86 to 0.91).
      CONCLUSIONS: Use of the PCHR is lower by women living in disadvantaged
      circumstances, but overall the record is retained and used by a high proportion
      of all mothers throughout the UK in their child's first year of life. PCHR use is
      endorsed in the National Service Framework for Children and has potential
      benefits which extend beyond the direct care of individual children.

PMID- 16455722
TI  - Management of diverticulitis.

PMID- 16455723
TI  - An alcoholic patient who continues to drink: case outcome.

PMID- 16455724
TI  - Challenge for doctors and policy makers.

PMID- 16455725
TI  - Patient's experience.

PMID- 16455726
TI  - Integrated learning.

PMID- 16455727
TI  - When should patients be held responsible for their lifestyle choices?

PMID- 16455728
TI  - Irritable bowel syndrome: diagnosis and management.

PMID- 16455729
TI  - Proteinuria.

PMID- 16455730
TI  - Wound assessment.

PMID- 16455732
TI  - Influence of Islam on smoking among Muslims.

PMID- 16455734
TI  - Just a family medical history?

PMID- 16455733
TI  - Conscientious objection in medicine.

PMID- 16455735
TI  - Implications of data protection legislation for family history.

PMID- 16455736
TI  - People seem confused about sensible drinking messages.

PMID- 16455737
TI  - How did UK cigarette makers reduce tar to 10 mg or less?

PMID- 16455738
TI  - Barriers to using warfarin in non-valvular atrial fibrillation.

PMID- 16455739
TI  - Cannabis and psychosis: Does cannabis really cause psychosis?

PMID- 16455740
TI  - Cannabis and psychosis: let's start from the null hypothesis.

PMID- 16455741
TI  - Severe hepatic injury and adulterated Chinese medicines.

PMID- 16455742
TI  - Pulmonary embolism in hospital practice: view from primary care is chest pain and
      breathlessness, but not together.

PMID- 16455743
TI  - Pulmonary embolism in hospital practice: certain crucial procedures were omitted.

PMID- 16455744
TI  - One step forward in engaging clinicians in IT.

PMID- 16455745
TI  - JAMA's policy does not go far enough.

PMID- 16455746
TI  - NHS Direct did not emerge from an evidence free void.

PMID- 16455747
TI  - FANMOD: a tool for fast network motif detection.
AB  - SUMMARY: Motifs are small connected subnetworks that a network displays in
      significantly higher frequencies than would be expected for a random network.
      They have recently gathered much attention as a concept to uncover structural
      design principles of complex biological networks. FANMOD is a tool for fast
      network motif detection; it relies on recently developed algorithms to improve
      the efficiency of network motif detection by some orders of magnitude over
      existing tools. This facilitates the detection of larger motifs in bigger
      networks than previously possible. Additional benefits of FANMOD are the ability
      to analyze colored networks, a graphical user interface and the ability to export
      results to a variety of machine- and human-readable file formats including comma
      separated values and HTML.

PMID- 16455748
TI  - A deterministic motif finding algorithm with application to the human genome.
AB  - MOTIVATION: We present a novel algorithm, MaMF, for identifying transcription
      factor (TF) binding site motifs. The method is deterministic and depends on an
      indexing technique to optimize the search process. On common yeast datasets, MaMF
      performs competitively with other methods. We also present results on a
      challenging group of eight sets of human genes known to be responsive to a
      diverse group of TFs. In every case, MaMF finds the annotated motif among the top
      scoring putative motifs. We compared MaMF against other motif finders on a larger
      human group of 21 gene sets and found that MaMF performs better than other
      algorithms. We analyzed the remaining high scoring motifs and show that many
      correspond to other TFs that are known to co-occur with the annotated TF motifs.
      The significant and frequent presence of co-occurring transcription factor
      binding sites explains in part the difficulty of human motif finding. MaMF is a
      very fast algorithm, suitable for application to large numbers of interesting
      gene sets.

PMID- 16455749
TI  - The LCB Data Warehouse.
AB  - The Linnaeus Centre for Bioinformatics Data Warehouse (LCB-DWH) is a web-based
      infrastructure for reliable and secure microarray gene expression data management
      and analysis that provides an online service for the scientific community. The
      LCB-DWH is an effort towards a complete system for storage (using the BASE
      system), analysis and publication of microarray data. Important features of the
      system include: access to established methods within R/Bioconductor for data
      analysis, built-in connection to the Gene Ontology database and a scripting
      facility for automatic recording and re-play of all the steps of the analysis.
      The service is up and running on a high performance server. At present there are
      more than 150 registered users. AVAILABILITY: An open functional version is
      available at https://dw.lcb.uu.se/index.phtml?i_login=test. User accounts are
      created upon request. Additional facilities including plug-ins, user
      documentation and a password protected data storage system are available from
      http://www.lcb.uu.se/lcbdw.php

PMID- 16455750
TI  - Detection of gene copy number changes in CGH microarrays using a spatially
      correlated mixture model.
AB  - MOTIVATION: Comparative genomic hybridization array experiments that investigate
      gene copy number changes present new challenges for statistical analysis and call
      for methods that incorporate spatial dependence between sequences along the
      chromosome. For this purpose, we propose a novel method called CGHmix. It is
      based on a spatially structured mixture model with three states corresponding to
      genomic sequences that are either unmodified, deleted or amplified. Inference is
      performed in a Bayesian framework. From the output, posterior probabilities of
      belonging to each of the three states are estimated for each genomic sequence and
      used to classify them. RESULTS: Using simulated data, CGHmix is validated and
      compared with both a conventional unstructured mixture model and with a recently
      proposed data mining method. We demonstrate the good performance of CGHmix for
      classifying copy number changes. In addition, the method provides a good estimate
      of the false discovery rate. We also present the analysis of a cancer related
      dataset. SUPPLEMENTARY INFORMATION: http://www.bgx.org.uk/papers.html

PMID- 16455751
TI  - PROFbval: predict flexible and rigid residues in proteins.
AB  - The mobility of a residue on the protein surface is closely linked to its
      function. The identification of extremely rigid or flexible surface residues can
      therefore contribute information crucial for solving the complex problem of
      identifying functionally important residues in proteins. Mobility is commonly
      measured by B-value data from high-resolution three-dimensional X-ray structures.
      Few methods predict B-values from sequence. Here, we present PROFbval, the first
      web server to predict normalized B-values from amino acid sequence. The server
      handles amino acid sequences (or alignments) as input and outputs normalized B
      value and two-state (flexible/rigid) predictions. The server also assigns a
      reliability index for each prediction. For example, PROFbval correctly identifies
      residues in active sites on the surface of enzymes as particularly rigid.
      AVAILABILITY: http://www.rostlab.org/services/profbval CONTACT:
      profbval@rostlab.org SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 16455752
TI  - affylmGUI: a graphical user interface for linear modeling of single channel
      microarray data.
AB  - SUMMARY: affylmGUI is a graphical user interface (GUI) to an integrated workflow
      for Affymetrix microarray data. The user is able to proceed from raw data (CEL
      files) to QC and pre-processing, and eventually to analysis of differential
      expression using linear models with empirical Bayes smoothing. Output of the
      analysis (tables and figures) can be exported to an HTML report. The GUI provides
      user-friendly access to state-of-the-art methods embodied in the Bioconductor
      software repository. AVAILABILITY: affylmGUI is an R package freely available
      from http://www.bioconductor.org. It requires R version 1.9.0 or later and tcl/tk
      8.3 or later and has been successfully tested on Windows 2000, Windows XP, Linux
      (RedHat and Fedora distributions) and Mac OS/X with X11. Further documentation is
      available at http://bioinf.wehi.edu.au/affylmGUI CONTACT: keith@wehi.edu.au.

PMID- 16455753
TI  - Predicting interactions in protein networks by completing defective cliques.
AB  - Datasets obtained by large-scale, high-throughput methods for detecting protein
      protein interactions typically suffer from a relatively high level of noise. We
      describe a novel method for improving the quality of these datasets by predicting
      missed protein-protein interactions, using only the topology of the protein
      interaction network observed by the large-scale experiment. The central idea of
      the method is to search the protein interaction network for defective cliques
      (nearly complete complexes of pairwise interacting proteins), and predict the
      interactions that complete them. We formulate an algorithm for applying this
      method to large-scale networks, and show that in practice it is efficient and has
      good predictive performance. More information can be found on our website
      http://topnet.gersteinlab.org/clique/ CONTACT: Mark.Gerstein@yale.edu
      SUPPLEMENTARY INFORMATION: Supplementary Materials are available at
      Bioinformatics online.

PMID- 16455754
TI  - Role of endoplasmic reticulum depletion and multidomain proapoptotic BAX and BAK
      proteins in shaping cell death after hypericin-mediated photodynamic therapy.
AB  - Both the commitment event and the modality of cell death in photodynamic therapy
      (PDT) remain poorly defined. We report that PDT with endoplasmic reticulum (ER)
      associating hypericin leads to an immediate loss of SERCA2 protein levels,
      causing disruption of Ca2+ homeostasis and cell death. Protection of SERCA2
      protein rescues ER-Ca2+ levels and prevents cell death, suggesting that SERCA2
      photodestruction with consequent incapability of the ER to maintain intracellular
      Ca2+ homeostasis is causal to cell killing. Apoptosis is rapidly initiated after
      ER-Ca2+ depletion and strictly requires the BAX/BAK gateway at the mitochondria.
      Bax-/-Bak-/- double-knockout (DKO) cells are protected from apoptosis but undergo
      autophagy-associated cell death as revealed by electron microscopy and
      biochemical analysis. Autophagy inhibitors, but not caspase antagonists,
      significantly reduce death of DKO cells, suggesting that sustained autophagy is
      lethal. Thus, following ER photodamage and consequent disruption of Ca2+
      homeostasis, BAX and BAK proteins model PDT-mediated cell killing, which is
      executed through apoptosis in their presence or via an autophagic pathway in
      their absence.

PMID- 16455756
TI  - Nitric oxide modulates proapoptotic and antiapoptotic properties of chemotherapy
      agents: the case of NO-pegylated epirubicin.
AB  - The use of the anthracycline epirubicin (EPI) is limited by the risk of a
      dilatory congestive heart failure that develops as a consequence of induction of
      a mitochondrial-dependent cardiomyocyte and endothelial cell apoptosis. Nitric
      oxide (NO) increases the antitumoral activity of several chemotherapics, while it
      provides protection against apoptosis induced by oxidative stress both in
      endothelial cells and cardiomyocytes. The aim of the present study was to
      investigate whether the addition of an NO-releasing moiety to a pegylated
      derivative of EPI (p-EPI-NO) confers to the drug a different cytotoxic profile
      against tumoral and normal cells. The cytotoxic profile of the drugs was
      investigated in Caco-2 cell line, in embryonic rat heart-derived myoblasts
      (H9c2), in adult cardiomyocytes, and in endothelial cells (HUVEC). p-EPI-NO was
      more efficient than EPI in inducing Caco-2 cell apoptosis, while it spared HUVEC,
      H9c2 cells and adult cardiomyocytes from EPI-induced toxicity. Exposure of cells
      to p-EPI-NO resulted in a NO-mediated inhibition of cellular respiration followed
      by mitochondrial membrane depolarization and cell death in Caco-2 cells but not
      in HUVEC and H9c2 cells in which mitochondrial membrane polarization was
      maintained at the expense of glycolytically generated ATP. These findings
      indicate that addition of an NO-releasing moiety to p-EPI increases the anti
      neoplastic activity of the drug, while it reduces its cytotoxicity against
      nonneoplastic cells.

PMID- 16455755
TI  - Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and
      caveolin-3 in skeletal muscle cells.
AB  - Skeletal muscle tissue is one of the main sites where glucose uptake occurs in
      response to insulin. The glucose transporter type-4 (GLUT4) is primarily
      responsible for the insulin-stimulated increase in glucose uptake. Upon insulin
      stimulation, GLUT4 is recruited from intracellular reserves to the plasma
      membrane. The molecular mechanisms that regulate the translocation of GLUT4 to
      the sarcolemma remain to be fully identified. Here, we demonstrate that GLUT4 is
      localized to perinuclear stores that contain flotillin-1, a marker of lipid
      rafts, in skeletal muscle cells. Stimulation with insulin for 10 min results in
      the translocation of flotillin-1/GLUT4-containing domains to the plasma membrane
      in a PI3K- and PKCzeta-dependent manner. We also demonstrate that caveolin-3, a
      marker of caveolae, is required for the insulin receptor-mediated activation of
      the PI3K-dependent pathway, which occurs 2 min after insulin stimulation. In
      fact, we demonstrate that lack of caveolin-3 significantly reduces insulin
      stimulated glucose uptake in caveolin-3 null myotubes by inhibiting both PI3K and
      Akt, as well as the movement of GLUT4 to the plasma membrane. Interestingly,
      caveolin-3 moves away from the plasma membrane toward the cytoplasm 5 min after
      insulin stimulation and temporarily interacts with flotillin-1/GLUT4-containing
      domains before they reach the sarcolemma, with the consequent movement of the
      insulin receptor from caveolin-3-containing domains to flotillin-1-containing
      domains. Such translocation temporally matches the insulin-stimulated movement of
      Cbl and CrkII in flotillin-1/GLUT4-containing domains, as well as the activation
      of the GDP-GTP exchange factor C3G. Disruption of flotillin-1-based domains
      prevents the activation of C3G, movement of GLUT4 to the sarcolemma, and glucose
      uptake in response to insulin. Thus, the activation of the Cbl/C3G/TC10-dependent
      pathway, which occurs before flotillin-1/GLUT4-containing domains reach the
      plasma membrane, is flotillin-1 mediated and follows the activation of the PI3K
      mediated signaling. Taken together, these results indicate that flotillin-1 and
      caveolin-3 may regulate muscle energy metabolism through the spatial and temporal
      segregation of key components of the insulin signaling.

PMID- 16455757
TI  - Increasing geographical inequalities in health in New Zealand, 1980-2001.
AB  - BACKGROUND: Recent studies have noted widening health inequalities between rich
      and poor areas in a number of OECD countries. This paper examines whether health
      in New Zealand has become more geographically polarized during the period 1980
      2001, a time of rapid social and economic changes in New Zealand society.
      METHODS: Mortality records for each year between 1980 and 2001 were extracted for
      consistent geographical areas: the 21 District Health Boards operating in New
      Zealand in 2001 and used to calculate male and female life expectancies for each
      area. The geographical inequalities in life expectancy were measured by
      calculating the slope index of inequality for each year between 1980 and 2001.
      RESULTS: Although overall life expectancy has increased during the period of
      study, New Zealand has experienced increased spatial polarization in health, with
      a particularly sharp rise in inequality during the late 1980s and early 1990s.
      Since the mid-1990s regional inequality has remained at stable but high levels.
      The polarization in mortality was mirrored by a growth in income inequality
      during the 1980s and 1990s. CONCLUSIONS: Health inequalities as expressed
      geographically in New Zealand have reached historically high levels and show
      little sign of abating. In order to tackle health inequalities, a greater
      commitment by the New Zealand government to a more redistributive social and
      economic agenda is required. Furthermore, issues of differentiated and health
      selective migration, emigration, and immigration need to be addressed as if these
      are important they should matter more for New Zealand than for almost any other
      developed nation-state.

PMID- 16455758
TI  - The incidence of coronary heart disease among Palestinians and Israelis in
      Jerusalem.
AB  - BACKGROUND: Lifestyle factors relevant to coronary risk factors differ between
      Palestinians and Israelis. Both have been exposed, albeit differently, to the
      stressors of the long-term conflict. We determined the incidence of coronary
      heart disease, previously unreported in Palestinians, in these Mediterranean
      populations and made international comparisons with the MONICA Programme.
      METHODS: We applied the rigorous World Health Organization MONICA protocol, which
      enables standardized international population-based comparisons, to determine all
      acute myocardial infarction events and coronary deaths among Palestinians and
      Israelis aged 25-74, residents of the Jerusalem district in 1997. RESULTS: We
      confirmed a total of 265 coronary events among 76,200 Arabs and 698 among 226,500
      Jews. Rates among Arabs were substantially higher than in Jews, particularly so
      in women. Age-adjusted rate ratios (RRs) for coronary events were 1.58 [95%
      confidence interval (95% CI) 1.34-1.87] among men and 2.37 (95% CI 1.81-3.10)
      among women. When restricted to coronary deaths, Arab: Jewish RRs were 2.79 (95%
      CI 2.09-3.73) in men and 2.66 (95% CI 1.77-4.00) in women. Compared with MONICA
      populations in 20 countries, Arabs ranked first in total coronary event rates and
      first in non-fatal myocardial infarction rates, exceeded populations in Finland,
      Scotland, and Northern Ireland, and showed striking differences from the
      participating Mediterranean centres. CONCLUSIONS: Coronary risk appears to be
      particularly high in Palestinian Arabs. Determinants of these unexpected findings
      should be sought and prevention programmes initiated.

PMID- 16455759
TI  - FAS inhibitor cerulenin reduces food intake and melanocortin receptor gene
      expression without modulating the other (an)orexigenic neuropeptides in chickens.
AB  - Cerulenin, a natural fatty acid synthase (FAS) inhibitor, and its synthetic
      analog C75 are hypothesized to alter the metabolism of neurons in the
      hypothalamus that regulate ingestive behavior to cause a profound decrease of
      food intake and an increase in metabolic rate, leading to body weight loss. The
      bulk of data exclusively originates from mammals (rodents); however, such effects
      are currently lacking in nonmammalian species. We have, therefore, addressed this
      issue in broiler chickens because this species is selected for high growth rate
      and high food intake and is prone to obesity. First, we demonstrate that FAS
      messenger and protein are expressed in the hypothalamus of chickens. FAS
      immunoreactivity was detected in a number of brain regions, including the nucleus
      paraventricularis magnocellularis and the nucleus infundibuli hypothalami, the
      avian equivalent of the mammalian arcuate nucleus, suggesting that FAS may be
      involved in the regulation of food intake. Second, we show that hypothalamic FAS
      gene expression was significantly (P < 0.05) decreased by overnight fasting
      similar to that in liver, indicating that hypothalamic FAS gene is regulated by
      energy status in chickens. Finally, to investigate the physiological consequences
      of in vivo inhibition of fatty acid synthesis on food intake, we administered
      cerulenin by intravenous injections (15 mg/kg) to 2-wk-old broiler chickens.
      Cerulenin administration significantly reduced food intake by 23 to 34% (P < 0.05
      to P < 0.0001) and downregulated FAS and melanocortin receptors 1, 4, and 5 gene
      expression (P < 0.05). However, the known orexigenic (neuropeptide Y, agouti gene
      related peptide, orexin, and orexin receptor) and anorexigenic (pro
      opiomelanocortin and corticotropin-releasing hormone) neuropeptide mRNA levels
      remained unchanged after cerulenin treatment. These results suggest that the
      catabolic effect of cerulenin in chickens may be mediated through the
      melanocortin system rather than the other neuropeptides known to be involved in
      food intake regulation.

PMID- 16455760
TI  - Water ingestion by rats fed a high-salt diet may be mediated, in part, by
      visceral osmoreceptors.
AB  - After surgical removal of all salivary secretions ("desalivation"), rats increase
      their consumption of water while eating dry laboratory chow. In the present
      experiments, desalivated rats drank even more water while they ate "powdered"
      high-salt food (i.e., <15-mg food particles). The Na+ concentration of systemic
      plasma in these animals was not elevated during or immediately after the meal,
      which suggests that cerebral osmoreceptors were not involved in mediating the
      increased water intake. A presystemic osmoregulatory signal likely stimulated
      thirst because the Na+ and water contents of the gastric chyme computed to a
      solution approximately 150 mM NaCl. In contrast, desalivated rats drank much
      smaller volumes of water while eating "pulverized" high-salt food (i.e., 60-140
      mg food particles), and the fluid mixture in the gastric chyme computed to
      approximately 280 mM NaCl solution. These and other findings suggest that the
      NaCl ingested in the powdered high-salt diet was dissolved in the gastric fluid
      and that duodenal osmoreceptors (or Na+-receptors) detected when the
      concentration of fluid leaving the stomach was elevated after each feeding bout,
      and promptly stimulated thirst, whereupon rats drank water until the gastric
      fluid was diluted back to isotonicity. However, when rats ate the pulverized high
      salt diet, much of the NaCl ingested may have been embedded in the gastric chyme
      and therefore was not accessible to visceral osmoreceptors once it emptied from
      the stomach. Consistent with that hypothesis, fluid intakes were increased
      considerably when desalivated rats drank 0.10 M NaCl instead of water while
      eating either powdered or pulverized high-salt food.

PMID- 16455761
TI  - Early postnatal chronic intermittent hypoxia modifies hypoxic respiratory
      responses and long-term phrenic facilitation in adult rats.
AB  - Acute isocapnic intermittent hypoxia elicits time-dependent, serotonin-dependent
      enhancement of phrenic motor output in anesthetized rats (phrenic long-term
      facilitation, pLTF). In adult rats, pLTF is enhanced by chronic intermittent
      hypoxia (CIH). To test the hypothesis that early postnatal CIH induces persistent
      modifications of ventilation and pLTF, we exposed male Sprague-Dawley rat pups on
      their first day of life to a CIH profile consisting of alternating room air and
      10% oxygen every 90 s for 30 days during daylight hours (RAIH) or to comparable
      exposures consisting of room air throughout (RARA). One month after cessation of
      CIH, respiratory responses were recorded using whole body plethysmography, and
      integrated phrenic nerve activity was recorded in urethane-anesthetized,
      vagotomized, paralyzed, and ventilated rats at baseline and after exposures to
      three 5-min hypoxic episodes [inspired O2 fraction (FiO2)=0.11] separated by 5
      min of hyperoxia (FiO2=0.5). RAIH rats displayed greater normoxic ventilation and
      also increased burst frequency compared with RARA rats (P<0.01). Ventilatory
      responses to hypoxia and short-term phrenic responses during acute hypoxic
      challenges were reduced in RAIH rats (P<0.01). Although pLTF was present in both
      RAIH and RARA rats, it was diminished in RAIH rats (minute activity: 74+/-2% in
      RARA vs. 55+/-5% in RAIH at 60 min; P<0.01). Thus we conclude that early
      postnatal CIH modifies normoxic and hypoxic ventilatory and phrenic responses
      that persist at 1 mo after cessation of CIH (i.e., metaplasticity) and markedly
      differ from previously reported increased neural plasticity changes induced by
      CIH in adult rats.

PMID- 16455762
TI  - Inhibition of caspase-1 in rat brain reduces spontaneous nonrapid eye movement
      sleep and nonrapid eye movement sleep enhancement induced by lipopolysaccharide.
AB  - Evidence suggests that IL-1beta is involved in promoting physiological nonrapid
      eye movement (NREM) sleep. IL-1beta has also been proposed to mediate NREM sleep
      enhancement induced by bacteria or their components. Mature and biologically
      active IL-1beta is cleaved from an inactive precursor by a cysteinyl aspartate
      specific protease (caspase)-1. This study aimed to test the hypothesis that
      inhibition in brain of the cleavage of biologically active IL-1beta will reduce
      in rats both spontaneous NREM sleep and NREM sleep enhancement induced by the
      peripheral administration of components of the bacterial cell wall. To test this
      hypothesis, rats were intracerebroventricularly administered the caspase-1
      inhibitor Ac-Tyr-Val-Ala-Asp chloromethyl ketone (YVAD; 3, 30, 300, and 1,500 ng)
      or were pretreated intracerebroventricularly with YVAD (300 ng) and then
      intraperitoneally injected with the gram-negative bacterial cell wall component
      LPS (250 microg/kg). Subsequent sleep-wake behavior was determined by standard
      polygraphic recordings. YVAD administration at the beginning of the light phase
      of the light-dark cycle significantly reduced time spontaneously spent in NREM
      sleep during the first 12 postinjection hours. YVAD pretreatment also completely
      prevented NREM sleep enhancement induced by peripheral LPS administration at the
      beginning of the dark phase. These results, in agreement with previous evidence,
      support the involvement of brain IL-1beta in physiological promotion of NREM
      sleep and in mediating NREM sleep enhancement induced by peripheral immune
      challenge.

PMID- 16455763
TI  - Peripheral metabolic responses to prolonged weight reduction that promote rapid,
      efficient regain in obesity-prone rats.
AB  - Weight regain after weight loss is the most significant impediment to long-term
      weight reduction. We have developed a rodent paradigm that models the process of
      regain after weight loss, and we have employed both prospective and cross
      sectional analyses to characterize the compensatory adaptations to weight
      reduction that may contribute to the propensity to regain lost weight. Obese rats
      were fed an energy-restricted (50-60% kcal) low-fat diet that reduced body weight
      by 14%. This reduced weight was maintained for up to 16 wk with limited
      provisions of the low-fat diet. Intake restriction was then removed, and the rats
      were followed for 56 days as they relapsed to the obese state. Prolonged weight
      reduction was accompanied by 1) a persistent energy gap resulting from an
      increased drive to eat and a reduced expenditure of energy, 2) a higher caloric
      efficiency of regain that may be linked with suppressed lipid utilization early
      in the relapse process, 3) preferential lipid accumulation in adipose tissue
      accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that
      underestimate the level of peripheral adiposity and likely influence the neural
      pathways controlling energy balance. Taken together, long-term weight reduction
      in this rodent paradigm is accompanied by a number of interrelated compensatory
      adjustments in the periphery that work together to promote rapid and efficient
      weight regain. These metabolic adjustments to weight reduction are discussed in
      the context of a homeostatic feedback system that controls body weight.

PMID- 16455764
TI  - Activation of subfornical organ neurons in rats through pre- and postsynaptic
      alpha-adrenoceptors.
AB  - The effects of noradrenaline (NA) and its analogs on subfornical organ (SFO)
      neurons in rat slice preparations were investigated by using whole cell patch
      clamp recording. In the current-clamp mode, the application of NA at 10-100
      microM produced membrane depolarization (63%, 17 responsive neurons/27 neurons
      tested) and hyperpolarization (22%, 6/27 neurons). In the voltage-clamp mode, NA
      application at 1-100 microM produced inward currents (69%, 42/61 neurons) and
      outward currents (23%, 14/61 neurons). These currents remained in the presence of
      TTX or both glutamate and GABA receptor antagonists. In most of the neurons
      (25/31 neurons) showing inward currents in the presence of NA, the membrane
      conductance was not changed by voltage ramps or hyperpolarizing pulse
      stimulation. Similar responses were obtained by the application of the alpha1
      agonist phenylephrine. The phenylephrine-induced inward currents were inhibited
      by the alpha1-antagonist prazosin. The alpha2-agonist clonidine decreased the
      frequency of spontaneous GABAergic inhibitory postsynaptic currents (4/10
      neurons). In addition, RT-PCR assay and immunohistochemical staining showed the
      existence of alpha1-adrenoceptors in the SFO. The results suggest that SFO
      neurons in rats are activated postsynaptically through alpha1-adrenoceptors and
      that the activation is enhanced by suppressing GABAergic inhibitory synaptic
      inputs through presynaptic alpha2-adrenoceptors.

PMID- 16455765
TI  - Insulin and growth hormone stimulate somatostatin receptor (SSTR) expression by
      inducing transcription of SSTR mRNAs and by upregulating cell surface SSTRs.
AB  - This study examined the effects of insulin (INS) and growth hormone (GH) on mRNA
      and functional expression of somatostatin receptors (SSTRs). Rainbow trout liver
      was used as a model system to evaluate the direct effects of INS and GH on mRNA
      expression of three SSTR subtypes characterized previously from this species:
      SSTR1A, SSTR1B, and SSTR2. INS and GH directly stimulated steady-state levels of
      all SSTR mRNAs in a concentration- and time-dependent manner; however, the
      pattern of expression was hormone and SSTR subtype specific. INS stimulated SSTR2
      expression to a greater extent than SSTR1A or SSTR1B expression, whereas GH
      stimulated SSTR2 and SSTR1B expression to a similar extent, with SSTR2 and SSTR1B
      expression being more responsive to GH than SSTR1A. Whether INS- or GH-stimulated
      SSTR expression resulted from altered rates of transcription and/or changes in
      mRNA stability also was investigated. Formation of nascent SSTR transcripts in
      nuclei isolated from rainbow trout hepatocytes was significantly stimulated by
      INS and GH. Neither INS nor GH, however, affected the stability of SSTR mRNAs.
      Functional expression of SSTRs was studied in Chinese hamster ovary (CHO-K1)
      cells stably transfected with SSTR1A or SSTR1B. Surface expression of functional
      SSTRs was stimulated by INS and GH. These findings indicate that INS and GH
      stimulate SSTR expression by regulating transcription of SSTR mRNAs and by
      increasing functional SSTRs on the cell surface, and they suggest that regulation
      of SSTRs may be important for the coordination of growth, development, and
      metabolism of vertebrates.

PMID- 16455766
TI  - Treatment of rats with calpain inhibitors prevents sepsis-induced muscle
      proteolysis independent of atrogin-1/MAFbx and MuRF1 expression.
AB  - Muscle wasting in sepsis is a significant clinical problem because it results in
      muscle weakness and fatigue that may delay ambulation and increase the risk for
      thromboembolic and pulmonary complications. Treatments aimed at preventing or
      reducing muscle wasting in sepsis, therefore, may have important clinical
      implications. Recent studies suggest that sepsis-induced muscle proteolysis may
      be initiated by calpain-dependent release of myofilaments from the sarcomere,
      followed by ubiquitination and degradation of the myofilaments by the 26S
      proteasome. In the present experiments, treatment of rats with one of the calpain
      inhibitors calpeptin or BN82270 inhibited protein breakdown in muscles from rats
      made septic by cecal ligation and puncture. The inhibition of protein breakdown
      was not accompanied by reduced expression of the ubiquitin ligases atrogin
      1/MAFbx and MuRF1, suggesting that the ubiquitin-proteasome system is regulated
      independent of the calpain system in septic muscle. When incubated muscles were
      treated in vitro with calpain inhibitor, protein breakdown rates and calpain
      activity were reduced, consistent with a direct effect in skeletal muscle.
      Additional experiments suggested that the effects of BN82270 on muscle protein
      breakdown may, in part, reflect inhibited cathepsin L activity, in addition to
      inhibited calpain activity. When cultured myoblasts were transfected with a
      plasmid expressing the endogenous calpain inhibitor calpastatin, the increased
      protein breakdown rates in dexamethasone-treated myoblasts were reduced,
      supporting a role of calpain activity in atrophying muscle. The present results
      suggest that treatment with calpain inhibitors may prevent sepsis-induced muscle
      wasting.

PMID- 16455767
TI  - The hydroosmotic response of frog urinary bladder to serosal hypertonicity is
      dependent on adenylate cyclase for its maintenance and affected by [Cl-]o
      changes.
AB  - The role of adenylate cyclase (AC) in the maintenance of the hydroosmotic
      response to serosal hypertonicity (SH) in anuran urinary bladder is disputed. In
      this study, norepinephrine (NE) significantly reversed the hydroosmotic response
      of Rana temporaria bladders in hypertonic medium (330 mosmol/kgH2O). The reversal
      was inhibited by yohimbine but was unaffected by prazosin and propranolol,
      indicating that NE action was mediated via alpha2-adrenergic receptors.
      Preincubation of bladders with indomethacin did not interfere with the inhibitory
      action of NE, contraindicating a role for prostaglandins. The SH hydroosmotic
      response was abolished in the presence of 5-n-ethyl-N-isopropyl amiloride (EIPA),
      but the antidiuretic hormone (ADH) hydroosmotic response was not. EIPA inhibits
      Na+/H+, known to be activated by cell shrinkage. An investigation of the anionic
      requirement of the SH hydroosmotic response revealed that replacement of bath Cl-
      with the nonpermeable anion gluconate reversibly abolished this response. In
      contrast, the hydroosmotic response to ADH was unaffected by Cl- removal;
      however, when Cl- was absent, it was no longer augmented in hypertonic bath. The
      SH response was inhibited by the Cl- channel blocker 5-nitro-2-(3
      phenylpropylamino)benzoate but not by the Na/K/2Cl inhibitor bumetanide. Our
      results show that not only the onset but also the maintenance of the SH
      hydroosmotic response is dependent on AC activity and does not differ in this
      respect to the ADH hydroosmotic response. The effect of modifying extracellular
      Cl- concentration, suggests that this anion, possibly functionally linked with
      Na+/H+ activity, may be involved in invoking the SH hydroosmotic response in
      anuran urinary bladder.

PMID- 16455768
TI  - Interleukin-1 mediates endothelin-1-induced fever and prostaglandin production in
      the preoptic area of rats.
AB  - The intracerebroventricular injection of endothelin-1 (ET-1) induces fever and
      increases PG levels in the cerebrospinal fluid of rats. Likewise, the injection
      of IL-1 into the preoptic area (POA) of the rat hypothalamus causes both fever
      and increased PG production. In this study, we conducted in vivo and in vitro
      experiments in the rat to investigate 1) the hypothalamic region involved in ET-1
      induced fever and PG biosynthesis and 2) whether hypothalamic IL-1 plays a role
      as a mediator of the above ET-1 activities. One hundred femtomoles of ET-1
      increased body temperature when injected in the POA of conscious Wistar rats;
      this effect was significantly counteracted by the coinjection of 600 pmol IL-1
      receptor antagonist (IL-1ra). In experiments on rat hypothalamic explants, 100 nM
      ET-1 caused a significant increase in PGE2 production and release from the whole
      hypothalamus and from the isolated POA, but not from the retrochiasmatic region,
      in 1-h incubations. Six nanomoles of IL-1ra or 10 nM of a cell-permeable
      interleukin-1 converting enzyme inhibitor completely counteracted the effect of
      ET-1 on PGE2 release from the POA. One hundred nanomoles ET-1 also caused a
      significant increase in IL-1beta immunoreactivity released into the bath solution
      of hypothalamic explants after 1 h of incubation, although during such time ET-1
      failed to modify the gene expression of IL-1beta and other pyrogenic cytokines
      within the hypothalamus. In conclusion, our results show that ET-1 increases IL-1
      production in the POA, and this effect appears to be correlated to ET-1-induced
      fever in vivo, as well as to PG production in vitro.

PMID- 16455769
TI  - Reduced stress- and cold-induced increase in energy expenditure in interleukin-6
      deficient mice.
AB  - Interleukin-6 (IL-6) deficient (-/-) mice develop mature onset obesity.
      Pharmacological studies have shown that IL-6 has direct lipolytic effects and
      when administered centrally increases sympathetic outflow. However, the metabolic
      functions of endogenous IL-6 are not fully elucidated. We aimed to investigate
      the effect of IL-6 deficiency with respect to cold exposure and cage-switch
      stress, that is, situations that normally increase sympathetic outflow. Energy
      metabolism, core temperature, heart rate, and activity were investigated in young
      preobese IL-6-/- mice by indirect calorimetry together with telemetry. Baseline
      measurements and the effect of cage-switch stress were investigated at
      thermoneutrality (30 degrees C) and at room temperature (20 degrees C). The
      effect of cold exposure was investigated at 4 degrees C. At 30 degrees C, the
      basal core temperature was 0.6 +/- 0.24 degrees C lower in IL-6-/- compared with
      wild-type mice, whereas the oxygen consumption did not differ significantly. The
      respiratory exchange ratio at 20 degrees C was significantly higher and the
      calculated fat utilization rate was lower in IL-6-/- mice. In response to cage
      switch stress, the increase in oxygen consumption at both 30 and 20 degrees C was
      lower in IL-6-/- than in wild-type mice. The increase in heart rate was lower in
      IL-6-/- mice at 30 degrees C. At 4 degrees C, both the oxygen consumption and
      core temperature were lower in IL-6-/- compared with wild-type mice, suggesting a
      lower cold-induced thermogenesis in IL-6-/- mice. The present results indicate
      that endogenous IL-6 is of importance for stress- and cold-induced energy
      expenditure in mice.

PMID- 16455770
TI  - Regulation of components of the brain and cardiac renin-angiotensin systems by
      17beta-estradiol after myocardial infarction in female rats.
AB  - The present study tested the hypothesis that 17beta-estradiol (E2) inhibits
      increases in angiotensin-converting enzyme (ACE) and ANG II type 1 receptor
      (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby,
      inhibits development of left ventricular (LV) dysfunction after MI. Age-matched
      female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2)
      ovariectomy + subcutaneous vehicle treatment (OVX + Veh), or 3) OVX +
      subcutaneous administration of a high dose of E2 (OVX + high-E2). After 2 wk,
      rats were randomly assigned to coronary artery ligation (MI) and sham operation
      groups and studied after 3 wk. E2 status did not affect LV function in sham rats.
      At 2-3 wk after MI, impairment of LV function was similar across MI groups, as
      measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance
      and activity were increased severalfold in all MI groups compared with respective
      sham animals and to similar levels across MI groups. In most brain nuclei, ACE
      and AT1R densities increased after MI. Unexpectedly, compared with the respective
      sham groups the relative increase was clearest (20-40%) in OVX + high-E2 MI rats,
      somewhat less (10-15%) in ovary-intact MI rats, and least (< 10-15%) in OVX + Veh
      MI rats. However, because in the sham group brain ACE and AT1R densities
      increased in the OVX + Veh rats and decreased in the OVX + high-E2 rats compared
      with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei
      were modestly higher (< 20%) in OVX + Veh MI rats than in the other two MI
      groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and
      amplifies the percent increases in ACE and AT1R densities in brain nuclei after
      MI, despite E2-induced downregulation in sham rats. Consistent with these minor
      variations in the tissue renin-angiotensin system, during the initial post-MI
      phase, E2 appears not to enhance or hinder the development of LV dysfunction.

PMID- 16455771
TI  - Evoked response potential markers for anesthetic and behavioral states.
AB  - The rodent whisker sensory system is a commonly used model of cortical
      processing; however, anesthetics cause profound differences in the shape and
      timing of evoked responses. Evoked response studies, especially those that use
      spatial mapping techniques, such as fMRI or optical imaging, will thus show
      significantly different results depending on the anesthesia used. To describe the
      effect of behavioral states and commonly used anesthetics, we characterized the
      early surface-evoked response potentials (ERPs) components (first ERP peak: gamma
      band 25-45 Hz; fast oscillation: 200-400 Hz; and very fast oscillation: 400-600
      Hz) using a 25-channel electrode array on the somatosensory cortex during whisker
      stimulation. We found significant differences in the ERP shape when
      ketamine/xylazine, urethane, propofol, isoflurane, and pentobarbital sodium were
      administered and during sleep and wake states. The highest ERP amplitudes were
      observed under propofol anesthesia and during quiet sleep. Under isoflurane, the
      ERP was nearly absent, except for a very late component, which was concombinant
      with burst synchronization. The slowest responses were seen under urethane and
      propofol anesthesia. Spatial mapping experiments that use electrical, NMR, or
      optical techniques must consider the anesthetic dependency of these signals,
      especially when stimulation protocols or electrical and metabolic responses are
      compared.

PMID- 16455773
TI  - Search for the feeding-entrainable circadian oscillator: a complex proposition.

PMID- 16455772
TI  - The dorsal vagal complex as a site for cocaine- and amphetamine-regulated
      transcript peptide to suppress gastric emptying.
AB  - Cocaine- and amphetamine-regulated transcript-derived peptides (CARTp) and
      corticotropin-releasing factor (CRF) alter feeding and gastrointestinal function
      after central administration, and the gastric inhibitory effects are mediated
      through CRF. We hypothesized that dorsal hindbrain effects of CARTp on gastric
      emptying are mediated by the vagus nerve and that the dorsal vagal complex (DVC)
      is a site of action for the gastric inhibitory effects of both CARTp and CRF.
      Rats were equipped with chronic intragastric fistulas and guide cannulas aimed at
      the fourth ventricle or the DVC. Fourth intracerebroventricular CARTp-induced
      suppression of 12 ml glucose (12.5%) gastric emptying during fill was blocked by
      subdiaphragmatic vagotomy. To establish whether the DVC may be a site of action
      for CARTp and/or CRF, intraparenchymal microinjections (0.25 microl) of CARTp
      (0.1 and 0.5 microg) and CRF (5 and 10 pmol) were administered in the DVC. Each
      dose, previously shown to be ineffective after fourth intracerebroventricular
      administration, suppressed gastric emptying during gastric fill vs. vehicle, but
      neither peptide changed gastric secretion volume or gastric acidity. The results
      indicate that the DVC is a target site for CRF and CARTp to inhibit gastric
      emptying and that the vagus mediates dorsal hindbrain effects of CARTp on gastric
      motor function.

PMID- 16455774
TI  - Comparative analysis of the effects of ghrelin and unacylated ghrelin on
      luteinizing hormone secretion in male rats.
AB  - Ghrelin, the endogenous ligand of GH secretagogue receptor type 1a, has emerged
      as pleiotropic modulator of diverse biological functions, including energy
      homeostasis and, recently, reproduction. Although inhibitory actions of ghrelin
      on LH secretion and puberty onset have been reported previously, the receptor
      mechanisms mediating these actions, and the potential gonadotropic effects of the
      unacylated isoform of ghrelin (UAG), remain unclear. In this work, the effects of
      single and repeated administration of ghrelin or UAG on LH secretion were
      compared in pubertal and adult male rats. In addition, the effects of ghrelin
      were assessed in models of transient or persistent hypergonadotropism. Daily
      injection of ghrelin or UAG throughout puberty similarly decreased LH levels and
      partially delayed balanopreputial separation. Likewise, chronic infusion of
      ghrelin or UAG to adult males resulted in significant decreases in circulating LH
      and FSH concentrations. Moreover, acute injection of ghrelin induced a transient
      reduction in LH levels in freely moving males, an effect that was fully mimicked
      by administration of UAG. Yet in contrast to ghrelin, UAG failed to modify GH
      secretion. Finally, injection of ghrelin moderately, but significantly, reduced
      the duration of LH secretory responses to the potent gonadotropin secretagogue
      kisspeptin-10, whereas ghrelin infusion in a model of chronic elevation of serum
      gonadotropin levels (the transgenic growth retarded male rat) evoked a
      significant reduction of LH concentrations. Altogether our present results
      further substantiate the inhibitory effect of ghrelin on basal and stimulated LH
      secretion in a wide array of experimental conditions. Moreover, our data are the
      first to demonstrate the ability of UAG, originally considered an inert form of
      the molecule, to mimic the actions of acylated ghrelin on LH release. These
      observations reinforce the contention that ghrelin, as putative signal for energy
      insufficiency, may operate as negative modifier of male puberty and LH secretion,
      an effect that might be, at least partially, conducted through a GH secretagogue
      receptor type 1a-independent mechanism.

PMID- 16455775
TI  - Mechanisms of adaptation to iodine deficiency in rats: thyroid status is tissue
      specific. Its relevance for man.
AB  - Many animals, man included, live in areas providing insufficient iodine (I) for
      optimal health. Degrees of I deficiency (ID) vary from mild-moderate to very
      severe, with quali- and quantitatively different negative consequences. To
      understand the mechanisms involved in adaptation to different grades of ID, we
      fed rats a low-iodine diet, plus additions resulting in a 250-fold range of I
      daily available to the thyroid, ranging from 5 mug (adequate) down to 0.02 microg
      I. We measured thyroid weight, total I, T(4), T(3), and type I 5' iodothyronine
      deiodinase (D1) activity, TSH, T(4), free T(4), and T(3) in plasma, T(4) and T(3)
      in 11 tissues, and two 5' deiodinase isoenzymes in four. TSH-independent thyroid
      autoregulation plays an important role in addition to TSH-dependent mechanisms in
      the adaptation to ID, avoiding a decrease of T(3) in plasma and most tissues,
      despite a marked decrease of plasma T(4), whereas extrathyroidal responses of D2
      mitigate T(3) deficiency in tissues in which T(3) is mostly generated from T(4).
      We focused on mild and moderate ID, the least investigated experimentally,
      despite its current frequency in industrialized countries. The novel and
      important finding of our study is that thyroid status cannot be defined for the
      animal as a whole: at all grades of ID, T(3) is simultaneously elevated, normal,
      and low in different tissues. Present findings in mild-moderate ID draw attention
      to the importance, for man, of the resulting hypothyroxinemia that may affect
      mental functions and neurodevelopment of the inhabitants, even when they do not
      have the increased TSH or clinical hypothyroidism, often wrongly attributed to
      them.

PMID- 16455776
TI  - Differential role of SH2-B and APS in regulating energy and glucose homeostasis.
AB  - SH2-B and APS, two members of a pleckstrin homology and SH2 domain-containing
      adaptor family, promote both insulin and leptin signaling in a similar fashion in
      cultured cells. In addition, APS mediates insulin-stimulated activation of the c
      Cbl/CAP/TC10 pathway in cultured adipocytes. Here we characterized genetically
      modified mice lacking SH2-B, APS, or both to determine the physiological roles of
      these two proteins in animals. Disruption of the SH2-B gene resulted in obesity,
      hyperglycemia, hyperinsulinemia, and glucose intolerance. Conversely, deletion of
      the APS gene did not alter adiposity, energy balance, and glucose metabolism.
      Energy intake, energy expenditure, fat content, body weight, and plasma insulin,
      leptin, glucose, and lipid levels were similar between APS(-/-) and WT
      littermates fed either normal chow or a high-fat diet. Moreover, deletion of APS
      failed to alter insulin and glucose tolerance. APS(-/-)/SH2-B(-/-) double
      knockout mice also developed energy imbalance, obesity, hyperleptinemia,
      hyperinsulinemia, hyperglycemia, and glucose intolerance; however, plasma leptin
      and insulin levels were significantly lower in APS(-/-)/SH2-B(-/-) than in SH2-B(
      /-) mice. These results suggest that SH2-B, but not APS, is a key positive
      regulator of energy and glucose metabolism in mice.

PMID- 16455777
TI  - Ribonucleic acid polymerase II binding subunit 3 (Rpb3), a potential nuclear
      target of insulin-like growth factor binding protein-3.
AB  - IGF-binding protein (IGFBP)-3 has intrinsic antiproliferative and proapoptotic
      functions that are independent of IGF binding and may involve nuclear
      localization. We determined that exogenous IGFBP-3 rapidly translocates to
      myoblast nuclei and that a 22-residue peptide containing the metal binding domain
      (MBD) and nuclear localization sequence (NLS) can similarly direct chimeric GFP
      into myoblast nuclei. Furthermore, a non-IGF-binding IGFBP-3 mutant inhibited
      myoblast proliferation without stimulating apoptosis. These results suggest that
      IGFBP-3 inhibits muscle cell growth in an IGF-independent manner that may be
      influenced by its rapid nuclear localization. We therefore identified IGFBP-3
      interacting proteins by screening a rat L6 myoblast cDNA library using the yeast
      two-hybrid assay and two N-terminal deletion mutants as bait: BP3/231 (231
      residues, L61 to K291) and BP3/111 (K181-K291). Proteins previously known to
      interact with IGFBP-3 as well as several novel proteins were identified,
      including RNA polymerase II binding subunit 3 (Rpb3). The domain necessary for
      Rpb3 binding was subsequently identified using different IGFBP-3 deletion mutants
      and was localized to the MBD/NLS epitope. Rpb3/IGFBP-3 binding was confirmed by
      coimmunoprecipitation assays with specific antisera, whereas a NLS mutant IGFBP-3
      did not associate with Rpb3, suggesting that a functional NLS is required. Rpb3
      facilitates recruitment of the polymerase complex to specific transcription
      factors and is necessary for the transactivation of many genes. Its association
      with IGFBP-3 provides a functional role for IGFBP-3 in the direct modulation of
      gene transcription.

PMID- 16455779
TI  - Exposure to repetitive versus varied stress during prenatal development generates
      two distinct anxiogenic and neuroendocrine profiles in adulthood.
AB  - Early life experiences can shape brain function and behavior in adulthood. The
      present study sought to elucidate the effects of repetitive, predictable vs.
      varied, unpredictable prenatal stress on sexually dichotomous neuroendocrine and
      anxiety-related behavioral responses in adult offspring. Rat dams were exposed
      repeatedly during the last week of pregnancy to no stress, only restraint stress
      [prenatal stress (PS)-restraint], or a randomized sequence of varied stressors
      (PS-random), and several behavioral and endocrine measures were assessed in adult
      male and female offspring. Repeated exposure to the same stressor (restraint)
      generated the most robust changes, including increased anxiety-related behaviors
      (both passive, measured on the elevated plus maze, and active, measured using
      defensive burying tests), a delayed and prolonged hypothalamic-pituitary-adrenal
      (HPA) axis response to stress in female offspring. Conversely, PS-restraint males
      showed no changes in anxiety-like behavior and had elevated basal ACTH and a
      blunted HPA response to stress; consistent with attenuated HPA responsivity was
      an increase in glucocorticoid receptor immunoreactivity in the hippocampus,
      suggesting increased negative feedback on the HPA axis in these animals. Prenatal
      exposure to a varied, unpredictable pattern of stressors did not have as much
      effect on HPA function, with most neuroendocrine measures residing intermediate
      to PS-restraint and control animals within each sex. Gonadal steroids were
      altered independent of the type of prenatal stress, but changes were measurable
      only in males (lower testosterone). The present data exemplify the differential
      sensitivity of the developing nervous and endocrine systems to stress, depending
      on not only gender but also the nature of the stressful experience endured by the
      mother during pregnancy.

PMID- 16455778
TI  - Insulin regulates islet alpha-cell function by reducing KATP channel sensitivity
      to adenosine 5'-triphosphate inhibition.
AB  - Glucose regulates pancreatic islet alpha-cell glucagon secretion directly by its
      metabolism to generate ATP in alpha-cells, and indirectly via stimulation of
      paracrine release of beta-cell secretory products, particularly insulin. How the
      cellular substrates of these pathways converge in the alpha-cell is not well
      known. We recently reported the use of the MIP-GFP (mouse insulin promoter-green
      fluorescent protein) mouse to reliably identify islet alpha- (non-green cells)
      and beta-cells (green cells), and characterized their ATP-sensitive K(+) (K(ATP))
      channel properties, showing that alpha-cell K(ATP) channels exhibited a 5-fold
      higher sensitivity to ATP inhibition than beta-cell K(ATP) channels. Here, we
      show that insulin exerted paracrine regulation of alpha-cells by markedly
      reducing the sensitivity of alpha-cell K(ATP) channels to ATP (IC(50) = 0.18 and
      0.50 mM in absence and presence of insulin, respectively). Insulin also
      desensitized beta-cell K(ATP) channels to ATP inhibition (IC(50) = 0.84 and 1.23
      mM in absence and presence of insulin, respectively). Insulin effects on both
      islet cell K(ATP) channels were blocked by wortmannin, indicating that insulin
      acted on the insulin receptor-phosphatidylinositol 3-kinase signaling pathway.
      Insulin did not affect alpha-cell A-type K(+) currents. Glutamate, known to also
      inhibit alpha-cell glucagon secretion, did not activate alpha-cell K(ATP) channel
      opening. We conclude that a major mechanism by which insulin exerts paracrine
      control on alpha-cells is by modulating its K(ATP) channel sensitivity to ATP
      block. This may be an underlying basis for the proposed sequential glucose
      insulin regulation of alpha-cell glucagon secretion, which becomes distorted in
      diabetes, leading to dysregulated glucagon secretion.

PMID- 16455780
TI  - Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone
      formation in vivo.
AB  - Molecular mechanisms underlying unloading-induced reduction of bone formation
      have not yet been fully understood. In vitro, Runx2 has been suggested to be
      involved in mechanical signaling in osteoblasts. However, the roles of Runx2 in
      vivo during the bone response to mechanical stimuli have not yet been known. The
      purpose of this paper was to examine the roles of Runx2 in unloading-induced bone
      loss in vivo. Tail suspension was conducted for 2 wk using 9- to 11-wk-old Runx2
      heterozygous knockout mice (Runx2(+/-)) and wild-type (Wt) littermates. Bones
      were subjected to two-dimensional micro-x-ray computed tomography, bone
      histomorphometry and RT-PCR analyses. Loss of half Runx2 gene dosage-exacerbated
      unloading-induced bone loss in trabecular and cortical envelopes. Unloading
      induced reduction in mineral apposition rate and bone formation rate in cortical
      bone as well as trabecular bone was exacerbated in Runx2(+/-) mice, compared with
      Wt mice. Bone resorption parameters were not significantly affected by unloading
      or Runx2(+/-) genotype. Basal Runx2 and osterix mRNA levels in bone were reduced
      by 50% in Wt, whereas unloading in Runx2(+/-) mice did not further alter Runx2
      and osterix mRNA levels. In contrast, osteocalcin mRNA levels were reduced by
      unloading, regardless of Runx2 gene dosage. These data demonstrated that full
      Runx2 gene dosage is required for maintaining normal function of osteoblasts in
      mechanical unloading or nonphysiological condition. Finally, we propose Runx2 as
      a critical target gene in unloading to alter osteoblastic activity and bone
      formation in vivo.

PMID- 16455781
TI  - Regulation of hepatic insulin-like growth factor-binding protein-1 gene
      expression by insulin: central role for mammalian target of rapamycin independent
      of forkhead box O proteins.
AB  - The expression of IGF-binding protein-1 (IGFBP-1) is induced in rat liver by
      dexamethasone and glucagon and is completely inhibited by 100 nM insulin. Various
      studies have implicated phosphatidylinositol 3-kinase, protein kinase B (Akt),
      phosphorylation of the transcription factors forkhead in rhabdomyosarcoma 1
      (Foxo1)/Foxo3, and the mammalian target of rapamycin (mTOR) in insulin's effect.
      In this study we examined insulin regulation of IGFBP-1 in both subconfluent and
      confluent hepatocytes. In subconfluent hepatocytes, insulin inhibition of IGFBP-1
      mRNA levels was blocked by inhibiting PI3 kinase activation, and there was a
      corresponding inhibition of Foxo1/Foxo3 phosphorylation. In these same cells,
      inhibition of the insulin effect by rapamycin occurred in the presence of insulin
      induced Foxo1/Foxo3 phosphorylation. In confluent hepatocytes, insulin could not
      activate the phosphatidylinositol 3-kinase (PI3 kinase)-Akt-Foxo1/Foxo3 pathway,
      but still inhibited IGFBP-1 gene expression in an mTOR-dependent manner. In
      subconfluent hepatocytes, the serine/threonine phosphatase inhibitor okadaic acid
      (100 nM) partially inhibited IGFBP-1 gene expression by 40%, but did not produce
      phosphorylation of either Akt or Foxo proteins. In contrast, 1 nm insulin
      inhibited the IGFBP-1 mRNA level by 40% and correspondingly activated Akt and
      Foxo1/Foxo3 phosphorylation to a level comparable to that observed with 100 nM
      insulin. These results suggest a potential role for a serine/threonine
      phosphatase(s) in the regulation of IGFBP-1 gene transcription, which is not
      downstream of mTOR and is independent of Akt. In conclusion, we have found that
      in rat liver, insulin inhibition of IGFBP-1 mRNA levels can occur in the absence
      of the phosphorylation of Foxo1/Foxo3, whereas activation of the mTOR pathway is
      both necessary and sufficient.

PMID- 16455782
TI  - Liver adenosine monophosphate-activated kinase-alpha2 catalytic subunit is a key
      target for the control of hepatic glucose production by adiponectin and leptin
      but not insulin.
AB  - The AMP-activated kinase (AMPK) is a serine threonine kinase that functions as a
      fuel sensor to regulate energy balance at both cellular and whole-body levels.
      Here we studied how hepatic AMPKalpha2 isoform affects hepatic glucose production
      and peripheral glucose uptake in vivo. We generated mice deleted for the
      AMPKalpha2 gene specifically in the liver (liveralpha2KO). Liveralpha2KO mice
      were glucose intolerant and hyperglycemic in the fasted state. Hyperglycemia was
      associated with a 50% higher endogenous glucose production than in controls as
      assessed in vivo. We then investigated whether this increased glucose production
      was sensitive to insulin. Insulin, when infused at a rate inducing physiological
      hyperinsulinemia, totally inhibited endogenous glucose production in
      liveralpha2KO mice, showing that they had normal insulin sensitivity. This was
      confirmed in vivo by normal insulin-induced phosphorylation of Akt and
      transcriptional regulation of the phosphoenolpyruvate carboxykinase, glucose-6
      phosphatase, and pyruvate kinase in liver during the fasted/fed transition.
      Leptin and adiponectin regulate hepatic glucose production, so we then infused
      these adipokines into liveralpha2KO mice. Neither of these adipokines regulated
      hepatic glucose production in mice lacking hepatic AMPKalpha2, whereas both did
      so in control mice. In conclusion, we show that the hepatic AMPKalpha2 isoform is
      essential for suppressing hepatic glucose production and maintaining fasting
      blood glucose levels in the physiological range. We also demonstrate that
      regulation of hepatic glucose production by leptin and adiponectin, but not
      insulin, requires hepatic AMPKalpha2 activity.

PMID- 16455783
TI  - Elevated glucose and diabetes promote interleukin-12 cytokine gene expression in
      mouse macrophages.
AB  - Inflammation is emerging as an important mechanism for micro- and macrovascular
      complication of diabetes. The macrophage plays a key role in the chronic
      inflammatory response in part by generating particular cytokines. IL-1beta, IL-6,
      IL12, IL-18, TNFalpha, and interferon-gamma are produced primarily in macrophages
      and have been associated with accelerated atherosclerosis and altered vascular
      wall function. In this study, we evaluated the effect and mechanism of high
      glucose (HG) on gene expression of these cytokines in mouse peritoneal
      macrophages (MPM). HG led to a 2-fold increase in the mRNA expression of these
      cytokines, with IL-12 showing the highest activation (5.4-fold) in a time
      dependent (3-12 h) and dose-dependent (10, 17.5, and 25 mmol/liter) manner. The
      effects were specific to HG because mannitol and 3-O-methyl-glucose had no effect
      on cytokine mRNA expression. HG also increased IL-12 protein accumulation from
      MPM. We also explored the role of induced and spontaneous diabetes on
      inflammatory cytokine expression in MPM. Increases in expression in MPM of
      multiple inflammatory cytokines, including a 20-fold increase in IL-12 mRNA, were
      observed in streptozotocin-induced type 1 diabetic mice as well as type 2
      diabetic db/db mice, suggesting that cytokine gene expression is increased by
      hyperglycemia in vivo. We next explored potential mechanisms of HG-induced
      increases in IL-12 mRNA. HG increased the activity of protein kinase C, p38 MAPK
      (p38), c-Jun terminal kinase, and inhibitory-kappaB kinase in MPM. Furthermore,
      inhibitors of these signaling pathways significantly reduced HG-induced IL-12
      mRNA expression in MPM. These results provide evidence for a potentially
      important mechanism linking elevated glucose and diabetes to inflammation.

PMID- 16455784
TI  - Pregnancy-enhanced endothelial nitric oxide synthase (eNOS) activation in uterine
      artery endothelial cells shows altered sensitivity to Ca2+, U0126, and wortmannin
      but not LY294002--evidence that pregnancy adaptation of eNOS activation occurs at
      multiple levels of cell signaling.
AB  - During pregnancy, vascular remodeling and vasoactive agents such as nitric oxide
      (NO) increase blood flow to the uteroplacental unit. Using our uterine artery
      endothelial cell (UAEC) culture model, based on cells from pregnant (P-UAEC) and
      nonpregnant (NP-UAEC) ewes, we investigate the relative physiological roles of
      Ca(2+) vs. kinase in the regulation of endothelial NO synthase (eNOS) activity.
      When Ca(2+) mobilization is fully inhibited using inhibitors of phospholipase C
      (PLC) (U73122) and the inositol triphosphate (IP3) receptor (IP3-R) (2-APB),
      significant residual eNOS activity remains in both P- and NP-UAEC. No change in
      ATP-stimulated ERK2, Akt, or eNOS phosphorylation is observed with U73122 (0.01-1
      microM) or 2-APB (1-50 microM). The MAPK kinase (MEK) 1/2 inhibitor U0126 (10
      microM) did not alter ATP-stimulated eNOS activity in P-UAEC, but potentiated the
      ATP response in NP-UAEC. Using two phosphatidylinositol 3-kinase (PI3-K)
      inhibitors, we observed no effect with LY294002 (10 microM) on eNOS activity in P
      and NP-UAEC, but wortmannin (10 microM) inhibited both P- and NP-UAEC eNOS
      activation. Expression of constitutively active Akt (ca-Akt) in UAEC resulted in
      slight elevation of basal eNOS activity, but relative ATP-stimulated eNOS
      activation was not altered by ca-Akt. Wortmannin continued to inhibit eNOS
      activation by ATP in the presence of ca-Akt; LY294002 still had no inhibitory
      effect. Our data indicate both [Ca(2+)](i) and multiple kinases are involved in
      the regulation of eNOS activity in our model. We report that pregnancy adaptation
      of eNOS activation includes the reduced sensitivity to ERK-mediated attenuation
      of eNOS activity and enhanced stimulation of eNOS activity through a wortmannin
      sensitive, LY294002-insensitive, Akt-independent mechanism.

PMID- 16455785
TI  - Hepatic cytochrome P-450 reductase-null mice show reduced transcriptional
      response to quercetin and reveal physiological homeostasis between jejunum and
      liver.
AB  - Using mice deficient in hepatic cytochrome P-450 oxidoreductase (POR), which
      disables the liver cytochrome P-450 system, we examined the metabolism and
      biological response of the anticarcinogenic flavonoid, quercetin. Profiling
      circulating metabolites revealed similar profiles over 72 h in wild-type (WT) and
      POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do
      not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that
      two- to threefold more genes responded significantly to quercetin in WT compared
      with KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s
      mediate many of the biological effects of quercetin, such as immune function,
      estrogen receptor signaling, and lipid, glutathione, purine, and amino acid
      metabolism, even though quercetin metabolism is not modified. The functional
      interpretation of expression data in response to quercetin (single dose of 7
      mg/animal) revealed a molecular relationship between the liver and jejunum. In WT
      animals, amino acid and sterol metabolism was predominantly modulated in the
      liver, fatty acid metabolism response was shared between the liver and jejunum,
      and glutathione metabolism was modulated in the small intestine. In contrast, KO
      animals do not regulate amino acid metabolism in the liver or small intestine,
      they share the control of fatty acid metabolism between the liver and jejunum,
      and regulation of sterol metabolism is shifted from the liver to the jejunum and
      that of glutathione metabolism from the jejunum to the liver. This demonstrates
      that the quercetin-mediated regulation of these biological functions in
      extrahepatic tissues is dependent on the functionality of the liver POR. In
      conclusion, using a systems biology approach to explore the contribution of
      hepatic phase 1 detoxification on quercetin metabolism demonstrated the
      resiliency and adaptive capacity of a biological organism in dealing with a
      bioactive nutrient when faced with a tissue-specific molecular dysfunction.

PMID- 16455786
TI  - Isolation, functional characterization, and transcriptome of Mastomys ileal
      enterochromaffin cells.
AB  - Although the enterochromaffin (EC) cell is one of the primary neuroendocrine
      regulatory cells of the small intestine, the lack of a purified cell system has
      precluded characterization of the cell and limited precise physiological
      evaluation. We developed methodology to obtain a pure population of Mastomys
      ileal EC cells, evaluated their functional regulation, and defined the
      transcriptome. Mastomys ilea were everted, end ligated, pronase-collagenase
      digested, and Nycodenz gradient centrifuged, and EC cells were collected by
      fluorescence-activated cell sorting (FACS) of acridine orange-labeled cells.
      Enrichment was confirmed by immunostaining of tryptophan hydroxylase and
      chromogranin A, specific EC cell markers, serotonin content, EC cell marker gene
      expression, and electron microscopy. Pituitary adenylate cyclase-activating
      polypeptide (PACAP), somatostatin, and gastrin receptor expression was determined
      by real-time RT-PCR. Live post-FACS-sorted cells were cultured, and the effects
      of forskolin, isoproterenol, acetylcholine, GABAA, PACAP-38, and gastrin on
      serotonin secretion were measured by ELISA. GeneChip Affymetrix profiling of FACS
      sorted cells was undertaken to obtain the EC cell transcriptome. FACS produced a
      >70-fold enrichment of EC cells with a serotonin content of 240 +/- 22 ng/mg
      protein. Preparations were 99 +/- 0.7% pure by immunostaining for tryptophan
      hydroxylase. Vasoactive intestinal peptide/PACAP receptor 1 (VPAC1) and
      somatostatin receptor 2 were present, whereas PACAP receptor 1 (PAC1) and CCK2
      receptors were undetectable. Forskolin, isoproterenol, and PACAP-38 stimulated
      serotonin secretion at EC50 values of 5 x 10(-10), 4.5 x 10(-10), and 1.2 x 10(
      9) M, respectively. Isoproterenol stimulated cAMP levels by approximately 3.5 +/-
      0.62-fold vs. unstimulated cells (EC50 of approximately 10(-9) M). Octreotide,
      acetylcholine, and GABAA inhibited serotonin secretion with IC50 values of 3 x
      10(-11), 3 x 10(-10), and 2.9 x 10(-10) M, respectively. Gastrin had no effect on
      serotonin secretion. The naive EC cell transcriptome revealed highly expressed EC
      cell marker genes, the absence of marker genes for other small intestinal cell
      types, and a receptor profile that included cholinergic, adrenergic,
      dopaminergic, serotoninergic, GABAergic, and prostaglandin receptors. We were
      able to isolate homogeneous preparations (>99%) of live ileal EC cells and
      demonstrated regulation of serotonin secretion as well as established the normal
      EC cell transcriptome. Application of this methodology to normal and diseased
      human ileum will facilitate the elucidation of the pathophysiology of EC cells.

PMID- 16455787
TI  - Comparison of rectoanal axial forces in health and functional defecatory
      disorders.
AB  - Anal manometry measures circumferential pressures but not axial forces that are
      responsible for defecation and contribute to fecal continence. Our aims were to
      investigate these mechanisms by measuring axial rectoanal forces with an
      intrarectal sphere or a latex balloon fixed at 8, 6, or 4 cm from the anal verge
      and connected to axial force and displacement transducers. Rectoanal forces and
      rectal pressures within a latex balloon were measured at baseline (i.e., at rest)
      and during maneuvers (i.e., squeeze, simulated evacuation, and a Valsalva
      maneuver) in 12 asymptomatic women and 12 women with symptoms of difficult
      defecation. Anal resting and squeeze pressures were also assessed by manometry
      and were similar in control patients and experimental patients. At rest, axial
      rectoanal forces were directed inward and increased as the device approached the
      anal verge. Control patients augmented this inward force when they squeezed and
      exerted an outward force during simulated expulsion and a Valsalva maneuver. The
      force change during maneuvers was also affected by device location and was
      highest at 4 cm from the verge. In experimental patients, the force at rest and
      the change in force during all maneuvers was lower than in control patients. The
      rectal pressure during a Valsalva maneuver was also lower in experimental
      patients than in control patients, suggestive of impaired propulsion. In
      conclusion, a subset of women with defecatory symptoms had weaker axial forces
      not only during expulsion but also during a Valsalva maneuver and when they
      squeezed (i.e., contracted) their pelvic floor muscles, suggestive of generalized
      pelvic floor weakness.

PMID- 16455788
TI  - Quantifying EGJ morphology and relaxation with high-resolution manometry: a study
      of 75 asymptomatic volunteers.
AB  - Our aim was to define normal esophagogastric junction (EGJ) morphology and
      relaxation characteristics using high-resolution manometry (HRM). To this end, 75
      asymptomatic controls underwent HRM with a solid-state manometric assembly
      incorporating 36 circumferential sensors spaced at 1-cm intervals positioned to
      record from the hypopharynx to the stomach. Ten 5-ml water swallows were
      obtained. EGJ relaxation was quantified by 1) nadir pressure, 2) the lowest 3-s
      mean residual pressure after swallow (E-sleeve), and 3) the transsphincteric
      gradient 2-6 s after swallowing measured from 2 cm above to 2 cm below the EGJ. A
      new parameter, integrated relaxation resistance (IRR), was also calculated. The
      IRR calculation accounted for both the duration of EGJ relaxation and
      instantaneous E-sleeve-type relaxation pressures during the entire interval of
      relaxation. The means and ranges (5-95th percentile) for nadir lower esophageal
      sphincter relaxation pressure (mean: 3.9 mmHg, range: 0-10.1 mmHg) and E-sleeve
      relaxation pressure (mean: 8.1 mmHg, range: 4.1-15.1 mmHg) were consistent with
      previously reported values. The mean relaxation interval was 7.95 +/- 0.2 s (mean
      +/- SE), whereas the median relaxation pressure during that interval was 10.7 +/-
      0.5 mmHg (mean +/- SE). Mean IRR was 1.3 mmHg/s (95th percentile: 3.0 mmHg/s).
      Mean EGJ length was 3.7 cm. In conclusion, HRM provides a seamless dynamic
      representation of pressure within and across the EGJ. In addition to providing
      conventional EGJ relaxation parameters, this technology also creates
      opportunities to quantify more precise measures of EGJ relaxation and morphology.

PMID- 16455789
TI  - Luminal leptin activates mucin-secreting goblet cells in the large bowel.
AB  - Leptin has been suggested to be involved in tissue injury and/or mucosal defence
      mechanisms. Here, we studied the effects of leptin on colonic mucus secretion and
      rat mucin 2 (rMuc2) expression. Wistar rats and ob/ob mice were used. Secretion
      of mucus was followed in vivo in the rat perfused colon model. Mucus secretion
      was quantified by ELISA, and rMuc2 mRNA levels were quantified by real-time RT
      PCR. The effects of leptin alone or in association with protein kinase C (PKC)
      and phosphatidylinositol 3-kinase (PI3K) inhibitors on mucin secreted by human
      mucus-secreting HT29-MTX cells were determined. Leptin was detected in the rat
      colonic lumen at substantial levels. Luminal perfusion of leptin stimulates mucus
      secreting goblet cells in a dose-dependent manner in vivo in the rat. Leptin (10
      nmol/l) increased mucus secretion by a factor of 3.5 and doubled rMuc2 mRNA
      levels in the colonic mucosa. There was no damage to mucosa 24 h after leptin,
      but the number of stained mucus cells significantly increased. Leptin-deficient
      ob/ob mice have abnormally dense mucus-filled goblet cells. In human colonic
      goblet-like HT29-MTX cells expressing leptin receptors, leptin increased mucin
      secretion by activating PKC- and PI3K-dependent pathways. This is the first
      demonstration that leptin, acting from the luminal side, controls the function of
      mucus-secreting goblet cells. Because the gel layer formed by mucus at the
      surface of the intestinal epithelium has a barrier function, our data may be
      relevant physiologically in defence mechanisms of the gastrointestinal tract.

PMID- 16455790
TI  - A targeted apoB38.9 mutation in mice is associated with reduced hepatic
      cholesterol synthesis and enhanced lipid peroxidation.
AB  - Familial hypobetalipoproteinemia (FHBL) due to truncation-specifying mutations of
      apolipoprotein B (apoB), which impair hepatic lipid export in very low-density
      lipoprotein (VLDL) particles, is associated with fatty liver. In an FHBL-like
      mouse with the apoB38.9 mutation, fatty liver develops despite reduced hepatic
      fatty acid synthesis. However, hepatic cholesterol contents in apoB38.9 mice are
      normal. We found that cholesterogenic enzymes (3-hydroxy-3-methylglutaryl
      coenzyme A reductase, sterol-C5-desaturase, and 7-dehydrocholesterol reductase)
      were consistently downregulated in two separate expression-profiling experiments
      using a total of 19 mice (n = 7 each for apob(+/+) and apob(+/38.9), and n = 5
      for apob(38.9/38.9)) and Affymetrix Mu74Av2 GeneChip microarrays. Results were
      confirmed by real-time PCR. Cholesterol synthesis rates in cultured hepatocytes
      were reduced by 35% and 25% in apob(38.9/38.9) and apob(+/38.9), respectively,
      vs. apob(+/+). Hepatic triglycerides and lipid peroxides, the latter measured by
      thiobarbituric acid-reactive substances (TBARS) assay, were significantly
      elevated in apob(+/38.9) (117%) and apob(38.9/38.9) (132%) vs. apob(+/+) (100%),
      as were mRNA expression of the microsomal lipid peroxidizing enzymes Cyp4A10 and
      Cyp4A14. Hepatic lipid peroxide levels were positively correlated with
      triglyceride contents (r = 0.601, P = 0.0065). Thus the fatty liver due to a VLDL
      secretion defect is associated with insufficient adaptation to triglyceride
      accumulation and with increased lipid peroxidation. In contrast, apoB38.9 mice
      effectively maintain cholesterol homeostasis in the liver, at least in part, by
      reducing hepatic cholesterol synthesis.

PMID- 16455791
TI  - Kidney plays a major role in ammonia homeostasis after portasystemic shunting in
      patients with cirrhosis.
AB  - The kidney plays an important role in ammonia metabolism. In this study the
      hypothesis was tested that the kidney can acutely diminish ammonia release after
      portacaval shunting. Thirteen patients with cirrhosis (6 female/7 male, age 54.4
      +/- 3.3 yr) were studied. Blood was sampled prior to and 1 h after transjugular
      intrahepatic stent-shunt (TIPSS) insertion from the portal vein, a hepatic vein,
      the right renal vein, and the femoral vein, and renal and liver plasma flow were
      measured. Prior to TIPSS, renal ammonia release was significantly higher than
      ammonia release from the splanchnic region, which was not significantly different
      from zero. TIPSS insertion did not change arterial ammonia concentration or
      ammonia release from the splanchnic region but reduced renal ammonia release into
      the circulation (P < 0.05) to values that were not different from zero. TIPSS
      resulted in a tendency toward increased venous-arterial ammonia concentration
      differences across leg muscle. Post-TIPSS ammonia efflux via portasystemic shunts
      was estimated to be seven times higher than renal efflux. Kidneys have the
      ability to acutely diminish systemic ammonia release after portacaval shunting.
      Diminished renal ammonia release and enhanced muscle ammonia uptake are important
      mechanisms by which the cirrhotic patient maintains ammonia homeostasis after
      portasystemic shunting.

PMID- 16455792
TI  - Longitudinal MRI in progressive supranuclear palsy and multiple system atrophy:
      rates and regions of atrophy.
AB  - The rate of brain atrophy and its relationship to clinical disease progression in
      progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not
      clear. Twenty-four patients with PSP, 11 with MSA-P (Parkinsonian variant), 12
      with Parkinson's disease, and 18 healthy control subjects were recruited for
      serial MRI scans, clinical assessments and formal neuropsychological evaluations
      in order to measure brain atrophy during life and its association with disease
      progression in PSP and MSA-P. Serial scans were registered and rates of whole
      brain atrophy calculated from the brain-boundary shift integral. Regional rates
      of atrophy were calculated in the brainstem (midbrain and pons), the cerebellum,
      the lateral and third ventricles as well as frontal and posterior inferior brain
      regions, by locally registering to a region of interest in order to derive a
      local boundary shift integral (BSI). 82% of recruited subjects completed serial
      MRI scans (17 PSP, 9 MSA-P, 9 Parkinson's disease patients and 18 healthy
      controls). Mean (SD) annualized rates of whole-brain atrophy were greatest in
      PSP: 1.2% (1.0%), three times that in controls. Mean (SD) midbrain atrophy rates
      in PSP, 2.2% (1.5%), were seven times greater than in healthy controls. In MSA-P,
      atrophy rates were greatest in the pons: 4.5% (3.2%), over 20 times that in
      controls and three times the rate of pontine atrophy in PSP. Atrophy rates in
      Parkinson's disease were not significantly different from control rates of
      atrophy. Variability in the atrophy rates was lower when calculated using the BSI
      rather than manual measurements. Worsening motor deficit was associated with
      midbrain atrophy in PSP, and ponto-cerebellar atrophy in MSA-P. Worsening
      executive dysfunction was associated with increased rates of frontal atrophy in
      PSP. Cerebellar atrophy rates were better discriminators of MSA-P than cross
      sectional volumes. We confirm that serial MRI can be applied to measure whole
      brain and regional atrophy rates in PSP and MSA-P. Regional rather than whole
      brain atrophy rates better discriminate PSP and MSA-P from healthy controls.
      Clinico-radiological associations suggest these regional atrophy rates have
      potential as markers of disease progression in trials of novel therapies.

PMID- 16455793
TI  - Shared blood and muscle CD8+ T-cell expansions in inclusion body myositis.
AB  - Inclusion body myositis (IBM) is the most frequent inflammatory myopathy over the
      age of fifty. Pathological findings suggest that two processes may contribute to
      IBM pathogenesis: a primary degenerative process affecting muscle fibre and/or an
      autoimmune process mediated by major histocompatibility complex (MHC) class-I
      restricted cytotoxic CD8+ T cells. Previous studies have demonstrated that muscle
      infiltrating CD8+ T cells in IBM display restricted expression of T-cell receptor
      (TCR)-BV families or evidenced oligoclonal T-cell expansions. This study was
      performed to investigate whether blood T cells similarly exhibit clonal
      expansions due to the recirculation of muscle-infiltrating T cells in the
      periphery. For this, we studied the T-cell repertoire of 17 IBM patients by
      complementarity-determining-region (CDR) 3 length distribution (immunoscope)
      analysis of TCR-B transcripts. Mean age was 68 years (range 53-88) and mean
      duration of the disease was 6.5 years (2-20). Oligoclonal T-cell expansions were
      observed in the blood of IBM patients. The quantitative average perturbation D
      index was significantly increased in IBM patients [D = 13.7% +/- 1.2%, mean +/-
      standard error of measurement (SEM)] as compared with 17 age-matched controls
      suffering from connective tissue diseases not associated with T-cell repertoire
      perturbation, that is, dermatomyositis (DM) and systemic sclerosis (9.3 +/- 0.6%,
      P < 0.005). Nevertheless, there was no correlation between the level of blood
      perturbation and muscle inflammation. Sorting experiments showed that these
      perturbations were due to oligoclonal expansions of CD8+ T cells. In the three
      IBM patients analysed, we could relate the blood expansions to T-cell clones also
      found in muscle. The clonally expanded blood T cells dramatically responded to
      interleukin-2 (IL-2) in vitro, suggesting that they had been primed in vivo,
      presumably in response to yet unknown muscle auto-antigens. Together, our results
      indicate that clonally expanded muscle-infiltrating CD8+ T cells re-circulate in
      the blood and support the concept of a CD8+ T-cell-mediated autoimmune component
      in IBM, similarly to what is observed in polymyositis (PM).

PMID- 16455794
TI  - Deciding how to decide: ventromedial frontal lobe damage affects information
      acquisition in multi-attribute decision making.
AB  - Ventromedial frontal lobe (VMF) damage is associated with impaired decision
      making. Recent efforts to understand the functions of this brain region have
      focused on its role in tracking reward, punishment and risk. However, decision
      making is complex, and frontal lobe damage might be expected to affect it at
      other levels. This study used process-tracing techniques to explore the effect of
      VMF damage on multi-attribute decision making under certainty. Thirteen subjects
      with focal VMF damage were compared with 11 subjects with frontal damage that
      spared the VMF and 21 demographically matched healthy control subjects.
      Participants chose rental apartments in a standard information board task drawn
      from the literature on normal decision making. VMF subjects performed the
      decision making task in a way that differed markedly from all other groups,
      favouring an 'alternative-based' information acquisition strategy (i.e. they
      organized their information search around individual apartments). In contrast,
      both healthy control subjects and subjects with damage predominantly involving
      dorsal and/or lateral prefrontal cortex pursued primarily 'attribute-based'
      search strategies (in which information was acquired about categories such as
      rent and noise level across several apartments). This difference in the pattern
      of information acquisition argues for systematic differences in the underlying
      decision heuristics and strategies employed by subjects with VMF damage, which in
      turn may affect the quality of their choices. These findings suggest that the
      processes supported by ventral and medial prefrontal cortex need to be
      conceptualized more broadly, to account for changes in decision making under
      conditions of certainty, as well as uncertainty, following damage to these areas.

PMID- 16455795
TI  - AlQoL 9 for measuring quality of life in alcohol dependence.
AB  - AIMS: Quality of life (QoL) is an important factor of outcome tracking and
      treatment in alcohol misuse. A 9-item QoL scale, AlQoL 9, obtained from the
      generic SF 36, is proposed as a measure that characterizes the QoL of alcohol
      dependent patients. Our objective was to study the psychometric properties of
      this subscale. METHODS: AlQoL 9 was evaluated in two study groups of patients
      with DSM-IV diagnosis of dependence: 104 inpatients, and 114 outpatients.
      Severity of dependence, alcohol consumption, psychiatric, and somatic
      comorbidities were assessed. We studied the global properties of AlQoL 9 and its
      structure. RESULTS: Cronbach alpha-coefficients in both populations indicated
      good internal consistency (0.71 and 0.85). Test-retest intraclass coefficients
      for a 2-day interval in hospital were in the range 0.57-0.78. Principal component
      analysis found a unidimensional scale. This subscale has properties that are
      consistent with the concept of QoL in alcohol dependence, i.e. lowered QoL
      compared with the general population, influenced by gender, and depression.
      CONCLUSIONS: AlQoL 9 epitomizes QoL in alcohol-dependence. It gives a global
      measurement with good psychometric properties. It could be used in clinical
      practice as a diagnosis and management support instrument and may also be useful
      in research for evaluating treatment efficacy.

PMID- 16455796
TI  - Concurrent use of alcohol and cocaine: differences in patterns of use and
      problems among users of crack cocaine and cocaine powder.
AB  - AIM: To investigate differences in alcohol and drug consumption behaviours and
      related problems among users of cocaine powder versus crack cocaine. METHODS: The
      sample of concurrent users of alcohol and cocaine (n = 102) was recruited from
      clinical and community (non-clinical) settings in London. Those recruited in the
      community were contacted by means of snowball sampling methods. Data were
      collected by means of face-to-face structured interviews. RESULTS: Heavy drinking
      was common. There were differences in alcohol consumption between users of
      cocaine powder and crack cocaine. Cocaine powder users reported more frequent
      heavy drinking than crack users. Heavy drinking often involved drinking excessive
      amounts over prolonged periods. Crack cocaine users reported more serious
      problems associated with cocaine, other illicit drugs, psychological and physical
      health problems, and acquisitive crime. CONCLUSIONS: Frequent heavy drinking
      represents a serious risk to the health of many cocaine users. The differences in
      alcohol consumption patterns confirm the importance of distinguishing between use
      of cocaine powder and crack cocaine. Few of the sample had received treatment for
      cocaine or alcohol problems. Healthcare professionals working in primary care or
      accident and emergency settings may need to be trained to detect, assess, and
      respond to concurrent alcohol and cocaine problems.

PMID- 16455797
TI  - Structures of wild-type and mutant human spermidine/spermine N1
      acetyltransferase, a potential therapeutic drug target.
AB  - Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme in the control of
      polyamine levels in human cells, as acetylation of spermidine and spermine
      triggers export or degradation. Increased intracellular polyamine levels
      accompany several types of cancers as well as other human diseases, and compounds
      that affect the expression, activity, or stability of SSAT are being explored as
      potential therapeutic drugs. We have expressed human SSAT from the cloned cDNA in
      Escherichia coli and have determined high-resolution structures of wild-type and
      mutant SSAT, as the free dimer and in binary and ternary complexes with CoA,
      acetyl-CoA (AcCoA), spermine, and the inhibitor N1,N11bis-(ethyl)-norspermine (BE
      3-3-3). These structures show details of binding sites for cofactor, substrates,
      and inhibitor and provide a framework to understand enzymatic activity,
      mutations, and the action of potential drugs. Two dimer conformations were
      observed: a symmetric form with two open surface channels capable of binding
      substrate or cofactor, and an asymmetric form in which only one of the surface
      channels appears capable of binding and acetylating polyamines. SSAT was found to
      self-acetylate lysine-26 in the presence of AcCoA and absence of substrate, a
      reaction apparently catalzyed by AcCoA bound in the second channel of the
      asymmetric dimer. These unexpected and intriguing complexities seem likely to
      have some as yet undefined role in regulating SSAT activity or stability as a
      part of polyamine homeostasis. Sequence signatures group SSAT with proteins that
      appear to have thialysine Nepsilon-acetyltransferase activity.

PMID- 16455798
TI  - The wild-derived inbred mouse strain SPRET/Ei is resistant to LPS and defective
      in IFN-beta production.
AB  - Although activation of Toll-like receptor 4 (TLR4)-positive cells is essential
      for eliminating Gram-negative bacteria, overactivation of these cells by the TLR4
      ligand LPS initiates a systemic inflammatory reaction and shock. Here we
      demonstrate that SPRET/Ei mice, derived from Mus spretus, exhibit a dominant
      resistance against LPS-induced lethality. This resistance is mediated by bone
      marrow-derived cells. Macrophages from these mice exhibit normal signaling and
      gene expression responses that depend on the myeloid differentiation factor 88
      adaptor protein, but they are impaired in IFN-beta production. The defect appears
      to be specific for IFN-beta, although the SPRET/Ei IFN-beta promoter is normal.
      In vivo IFN-beta induction by LPS or influenza virus is very low in SPRET/Ei
      mice, but IFN-beta-treatment restores the sensitivity to LPS, and IFN type 1
      receptor-deficient mice are also resistant to LPS. Because of the defective
      induction of IFN-beta, these mice are completely resistant to Listeria
      monocytogenes and highly sensitive to Leishmania major infection. Stimulation of
      SPRET/Ei macrophages leads to rapid down-regulation of IFN type 1 receptor mRNA
      expression, which is reflected in poor induction of IFN-beta-dependent genes.
      This finding indicates that the resistance of SPRET/Ei mice to LPS is due to
      disruption of a positive-feedback loop that amplifies IFN-beta production. In
      contrast to TLR4-deficient mice, SPRET/Ei mice resist both LPS and sepsis induced
      with Klebsiella pneumoniae.

PMID- 16455799
TI  - Anthrax lethal factor and edema factor act on conserved targets in Drosophila.
AB  - Many bacterial toxins act on conserved components of essential host-signaling
      pathways. One consequence of this conservation is that genetic model organisms
      such as Drosophila melanogaster can be used for analyzing the mechanism of toxin
      action. In this study, we characterize the activities of two anthrax virulence
      factors, lethal factor (LF) and edema factor, in transgenic Drosophila. LF is a
      zinc metalloprotease that cleaves and inactivates most human mitogen-activated
      protein kinase (MAPK) kinases (MAPKKs). We found that LF similarly cleaves the
      Drosophila MAPK kinases Hemipterous (Hep) and Licorne in vitro. Consistent with
      these observations, expression of LF in Drosophila inhibited the Hep/c-Jun N
      terminal kinase pathway during embryonic dorsal closure and the related process
      of adult thoracic closure. Epistasis experiments confirmed that LF acts at the
      level of Hep. We also found that LF inhibits Ras/MAPK signaling during wing
      development and that LF acts upstream of MAPK and downstream of Raf, consistent
      with LF acting at the level of Dsor. In addition, we found that edema factor, a
      potent adenylate cyclase, inhibits the hh pathway during wing development,
      consistent with the known role of cAMP-dependent PKA in suppressing the Hedgehog
      response. These results demonstrate that anthrax toxins function in Drosophila as
      they do in mammalian cells and open the way to using Drosophila as a
      multicellular host system for studying the in vivo function of diverse toxins and
      virulence factors.

PMID- 16455800
TI  - Roles of the anaphase-promoting complex/cyclosome and of its activator Cdc20 in
      functional substrate binding.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin
      protein ligase that targets for degradation cell-cycle regulatory proteins during
      exit from mitosis and in the G1 phase of the cell cycle. The activity of APC/C in
      mitosis and in G1 requires interaction with the activator proteins Cdc20 and
      Cdh1, respectively. Substrates of APC/C-Cdc20 contain a recognition motif called
      the "destruction box" (D-box). The mode of the action of APC/C activators and
      their possible role in substrate binding remain poorly understood. Several
      investigators suggested that Cdc20 and Cdh1 mediate substrate recognition,
      whereas others proposed that substrates bind to APC/C or to APC/C-activator
      complexes. All these studies used binding assays, which do not necessarily
      indicate that substrate binding is functional and leads to product formation. In
      the present investigation we examined this problem by an "isotope-trapping"
      approach that directly demonstrates productive substrate binding. With this
      method we found that the simultaneous presence of both APC/C and Cdc20 is
      required for functional substrate binding. By contrast, with conventional binding
      assays we found that either Cdc20 or APC/C can bind substrate by itself, but only
      at low affinity and relaxed selectivity for D-box. Our results are consistent
      with models in which interaction of substrate with specific binding sites on both
      APC/C and Cdc20 is involved in selective and productive substrate binding.

PMID- 16455801
TI  - Structural and function analyses of the global regulatory protein SarA from
      Staphylococcus aureus.
AB  - The sarA locus in Staphylococcus aureus controls the expression of many virulence
      genes. The sarA regulatory molecule, SarA, is a 14.7-kDa protein (124 residues)
      that binds to the promoter region of target genes. Here we report the 2.6 A
      resolution x-ray crystal structure of the dimeric winged helix SarA protein,
      which differs from the published SarA structure dramatically. In the crystal
      packing, multiple dimers of SarA form a scaffold, possibly via divalent cations.
      Mutations of individual residues within the DNA-binding helix-turn-helix and the
      winged region as well as within the metal-binding pocket implicate basic residues
      R84 and R90 within the winged region to be critical in DNA binding, whereas
      acidic residues D88 and E89 (wing), D8 and E11 (metal-binding pocket), and
      cysteine 9 are essential for SarA function. These data suggest that the winged
      region of the winged helix protein participates in DNA binding and activation,
      whereas the putative divalent cation binding pocket is only involved in gene
      function.

PMID- 16455802
TI  - N-glucuronidation of the platelet-derived growth factor receptor tyrosine kinase
      inhibitor 6,7-(dimethoxy-2,4-dihydroindeno[1,2-C]pyrazol-3-yl)-(3-fluoro-phenyl)
      amine by human UDP-glucuronosyltransferases.
AB  - The potential cancer therapeutic agent, 6,7-(dimethoxy-2, 4-dihydroindeno[1,2
      c]pyrazol-3-yl)-(3-fluoro-phenyl)-amine (JNJ-10198409), formed three N
      glucuronides that were positively identified by liquid chromatography-tandem mass
      spectrometry and NMR as N-amine-glucuronide (Glu-A), 1-N-pyrazole-glucuronide
      (Glu-B), and 2-N-pyrazole-glucuronide (Glu-C). All three N-glucuronides were
      detected in rat liver microsomes, whereas only Glu-A and -B were found in monkey
      and human liver microsomes. In contrast to common glucuronides, Glu-B was
      completely resistant to beta-glucuronidase. Kinetic analyses revealed that
      glucuronidation of JNJ-10198409 in human liver microsomes exhibited atypical
      kinetics that may be described by a two-site binding model. For the high affinity
      binding, K(m) values were 1.2 and 5.0 microM, and V(max) values were 2002 and
      2,403 nmol min(-1) mg(-1) for Glu-A and Glu-B, respectively. Kinetic constants of
      low affinity binding were not determined due to low solubility of the drug. Among
      the human UDP-glucuronosyltransferases (UGTs) tested, UGT1A9, 1A8, 1A7, and 1A4
      were the most active isozymes to produce Glu-A; for the formation of Glu-B,
      UGT1A9 was the most active enzyme, followed by UGT1A3, 1A7, and 1A4.
      Glucuronidation of JNJ-10198409 by those UGT1A enzymes followed classic Michaelis
      Menten kinetics. In contrast, no glucuronides were formed by all UGT2B isozymes
      tested, including UGT2B4, 2B7, 2B15, and 2B17. Collectively, these results
      suggested that glucuronidation of JNJ-10198409 in human liver microsomes is
      catalyzed by multiple UGT1A enzymes. Since UGT1A enzymes are widely expressed in
      various tissues, it is anticipated that both hepatic and extrahepatic
      glucuronidation will likely contribute to the elimination of the drug in humans.
      Additionally, conjugation at the nitrogens of the pyrazole ring represents a new
      structural moiety for UGT1A-mediated reactions.

PMID- 16455804
TI  - Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction
      between fexofenadine and probenecid.
AB  - Fexofenadine, a nonsedating antihistamine drug, is effective for the treatment of
      seasonal allergic rhinitis and chronic urticaria. Simultaneous administration of
      probenecid increases the plasma concentration of fexofenadine due to an
      inhibition of its renal elimination in healthy volunteers (Clin Pharmacol Ther
      77:17-23, 2005). The purpose of the present study is to investigate the
      possibility that the drug-drug interaction between fexofenadine and probenecid
      involves the renal basolateral uptake process. The uptake of fexofenadine was
      determined in HEK293 cells expressing human organic anion transporter 1
      (OAT1/SLC22A6), OAT2 (SLC22A7), OAT3 (SLC22A8), and organic cation transporter 2
      (OCT2/SLC22A2). Only hOAT3-HEK showed a significantly greater accumulation of
      fexofenadine than that in vector-HEK, which was saturable with K(m) and V(max)
      values of 70.2 microM and 120 pmol/min/mg protein, respectively. Inhibition
      potency of probenecid for the uptake of fexofenadine was compared between hOAT3
      and organic anion-transporting peptide 1B3 (hOATP1B3), a transporter responsible
      for the hepatic uptake of fexofenadine (Drug Metab Dispos 33:1477-1481, 2005).
      The K(i) values were determined to be 1.30 and 130 microM for hOAT3 and hOATP1B3,
      respectively, with Hill coefficients of 0.76 and 0.64, respectively. The K(i)
      value of probenecid for hOAT3, but not for hOATP1B3, was significantly lower than
      the maximum unbound plasma concentration of probenecid at clinical dosages. These
      results suggest that the renal drug-drug interaction between fexofenadine and
      probenecid is probably explained by an inhibition of the renal uptake of
      fexofenadine via hOAT3, at least in part.

PMID- 16455803
TI  - Influence of erythromycin on the pharmacokinetics of ximelagatran may involve
      inhibition of P-glycoprotein-mediated excretion.
AB  - A pharmacokinetic interaction between erythromycin and ximelagatran, an oral
      direct thrombin inhibitor, was demonstrated in this study in healthy volunteers.
      To investigate possible interaction mechanisms, the effects of erythromycin on
      active transport mediated by P-glycoprotein (P-gp) in vitro in Caco-2 and P-gp
      over-expressing Madin-Darby canine kidney-human multidrug resistance-1 cell
      preparations and on biliary excretion of melagatran in rats were studied. In
      healthy volunteers (seven males and nine females; mean age 24 years) receiving a
      single dose of ximelagatran 36 mg on day 1, erythromycin 500 mg t.i.d. on days 2
      to 5, and a single dose of ximelagatran 36 mg plus erythromycin 500 mg on day 6,
      the least-squares mean estimates (90% confidence intervals) for the ratio of
      ximelagatran with erythromycin to ximelagatran given alone were 1.82 (1.64-2.01)
      for the area under the concentration-time curve and 1.74 (1.52-2.00) for the
      maximum plasma concentration of melagatran, the active form of ximelagatran.
      Neither the slope nor the intercept of the melagatran plasma concentration-effect
      relationship for activated partial thromboplastin time statistically
      significantly differed as a function of whether or not erythromycin was
      administered with ximelagatran. Ximelagatran was well tolerated regardless of
      whether it was administered with erythromycin. Erythromycin inhibited P-gp
      mediated transport of both ximelagatran and melagatran in vitro and decreased the
      biliary excretion of melagatran in the rat. These results indicate that the
      mechanism of the pharmacokinetic interaction between oral ximelagatran and
      erythromycin may involve inhibition of transport proteins, possibly P-gp,
      resulting in decreased melagatran biliary excretion and increased bioavailability
      of melagatran.

PMID- 16455806
TI  - In vitro p-glycoprotein inhibition assays for assessment of clinical drug
      interaction potential of new drug candidates: a recommendation for probe
      substrates.
AB  - Because modulation of P-glycoprotein (Pgp) through inhibition or induction can
      lead to drug-drug interactions by altering intestinal, central nervous system,
      renal, or biliary efflux, it is anticipated that information regarding the
      potential interaction of drug candidates with Pgp will be a future regulatory
      expectation. Therefore, to be able to utilize in vitro Pgp inhibition findings to
      guide clinical drug interaction studies, the utility of five probe substrates
      (calcein-AM, colchicine, digoxin, prazosin, and vinblastine) was evaluated by
      inhibiting their Pgp-mediated transport across multidrug resistance-1-transfected
      Madin-Darby canine kidney cell type II monolayers with 20 diverse drugs having
      various degrees of Pgp interaction (e.g., efflux ratio, ATPase, and calcein-AM
      inhibition). Overall, the rank order of inhibition was generally similar with
      IC(50) values typically within 3- to 5-fold of each other. However, several
      notable differences in the IC(50) values were observed. Digoxin and prazosin were
      the most sensitive probes (e.g., lowest IC(50) values), followed by colchicine,
      vinblastine, and calcein-AM. Inclusion of other considerations such as a large
      dynamic range, commercially available radiolabel, and a clinically meaningful
      probe makes digoxin an attractive probe substrate. Therefore, it is recommended
      that digoxin be considered as the standard in vitro probe to investigate the
      inhibition profiles of new drug candidates. Furthermore, this study shows that it
      may not be necessary to generate IC(50) values with multiple probe substrates for
      Pgp as is currently done for cytochrome P450 3A4. Finally, a strategy integrating
      results from in vitro assays (efflux, inhibition, and ATPase) is provided to
      further guide clinical interaction studies.

PMID- 16455805
TI  - Rifampicin induction of CYP3A4 requires pregnane X receptor cross talk with
      hepatocyte nuclear factor 4alpha and coactivators, and suppression of small
      heterodimer partner gene expression.
AB  - Bile acids and drugs activate pregnane X receptor (PXR) to induce CYP3A4, which
      is the predominant cytochrome P450 enzyme expressed in the liver and intestine
      and plays a critical role in detoxifying bile acids and drugs, and protecting
      against cholestasis. The aim of this study is to investigate the molecular
      mechanism of PXR cross talk with other nuclear receptors and coactivators in
      regulating human CYP3A4 gene transcription. Rifampicin dose dependently induced
      the CYP3A4 but inhibited small heterodimer partner (SHP) mRNA expression levels
      in primary human hepatocytes. Rifampicin strongly stimulated PXR and hepatocyte
      nuclear factor 4alpha (HNF4alpha) interaction, and CYP3A4 reporter activity,
      which was further stimulated by peroxisome proliferators-activated receptorgamma
      co-activator 1alpha (PGC-1alpha) and steroid receptor coactivator-1 (SRC-1) but
      inhibited by SHP. Mutation of the putative HNF4alpha binding site in the distal
      xenobiotic responsive element module did not affect CYP3A4 basal promoter
      activity and synergistic stimulation by PXR and HNF4alpha. Chromatin
      immunoprecipitation assays revealed that rifampicin-activated PXR recruited
      HNF4alpha and SRC-1 to the CYP3A4 chromatin. On the other hand, SHP reduced PXR
      recruitment of HNF4alpha and SRC-1 to the CYP3A4 chromatin. The human SHP
      promoter was stimulated by HNF4alpha and PGC-1alpha. Upon activation by
      rifampicin, PXR inhibited SHP promoter activity. Results suggest that PXR
      strongly induces CYP3A4 gene transcription by interacting with HNF4alpha, SRC-1,
      and PGC-1alpha. PXR concomitantly inhibits SHP gene transcription and maximizes
      the PXR induction of the CYP3A4 gene in human livers. Drugs targeted to PXR may
      be developed for treating cholestatic liver diseases induced by bile acids and
      drugs.

PMID- 16455807
TI  - Effect of P-glycoprotein on intestinal absorption and brain penetration of
      antiallergic agent bepotastine besilate.
AB  - The antiallergic agent bepotastine besilate is a nonsedating, second-generation
      H1-antagonist with high oral absorption and negligible distribution into brain.
      To clarify the role of P-glycoprotein (P-gp) in the pharmacokinetics of
      bepotastine, intestinal absorption and brain penetration studies were performed.
      [(14)C]Bepotastine transport in P-gp-overexpressed LLC-PK1 cells indicated that
      bepotastine was a substrate of P-gp. The affinity of bepotastine to P-gp
      estimated by ATPase activity assay was low, with a K(m) value of 1.25 mM. After
      i.v. administration, the brain/plasma free concentration ratio in mdr1-knockout
      mice was 3 times higher than that in wild-type mice. The in situ intestinal
      absorption studies of [(14)C]bepotastine in rats showed a clear regional
      difference, showing highest permeability at the upper part of small intestine
      with a decreasing permeability in the descending part of small intestine. The
      apparent absorption rate constant (ka) of [(14)C]bepotastine in the small
      intestine was greatly increased by cyclosporin A and verapamil, especially in the
      distal portion, and the site-specific absorption of [(14)C]bepotastine
      disappeared. The concentration dependence of ka of [(14)C]bepotastine was
      observed with a higher ka at higher concentration (20 mM) compared with that at
      lower concentration (1 microM). In conclusion, bepotastine is a substrate for P
      gp, and P-gp clearly limited the brain distribution of bepotastine, whereas the
      effect of P-gp on intestinal absorption of bepotastine was minimal, presumably
      because of high membrane permeability at the upper region of small intestine
      where P-gp is less expressed. Such intestinal absorption property of bepotastine
      is distinctly different from the low membrane-permeable P-gp substrate
      fexofenadine.

PMID- 16455808
TI  - Rat pharmacokinetics and pharmacodynamics of a sustained release formulation of
      the GABAA alpha5-selective compound L-655,708.
AB  - The pharmacokinetic and pharmacodynamic (i.e., receptor occupancy) properties of
      L-655,708, a compound with selectivity for alpha5-over alpha1-, alpha2-, and
      alpha3-containing GABA(A) receptors, were examined in rats with the aim of
      developing a formulation that would give sustained (up to 6 h) and selective
      occupancy of alpha5-containing GABA(A) receptors suitable for behavioral studies.
      Standard rat pharmacokinetic analyses showed that L-655,708 has a relatively
      short half-life with kinetics in the brain mirroring those in the plasma. In vivo
      binding experiments showed that plasma concentrations of around 100 ng/ml gave
      relatively selective in vivo occupancy of rat brain alpha5-versus alpha1-, alpha2
      , and alpha3-containing GABA(A) receptors. Therefore, this plasma concentration
      was chosen as a target to achieve relatively selective occupancy of alpha5
      containing receptors using s.c. implantations of L-655,708 (0.4, 1.5, or 2.0 mg)
      formulated into tablets of various size (20 or 60 mg) containing different
      amounts of L-655,708 and combinations of low and high viscosity hydroxypropyl
      methylcellulose (LV- and HV-HPMC). The optimum formulation, 1.5 mg of L-655,708
      compressed into a 60-mg tablet with 100% HV-HPMC, resulted in relatively constant
      plasma concentrations being maintained for at least 6 h with very little
      difference between C(max) concentrations (125-150 ng/ml) and plateau
      concentrations (100-125 ng/ml). In vivo binding experiments confirmed the
      selective occupancy of rat brain alpha5-over alpha1-, alpha2-, and alpha3
      containing GABA(A) receptors.

PMID- 16455809
TI  - Transferability of six pesticides from agricultural sprayer surfaces.
AB  - Secondary exposure to pesticide residues on the external surfaces of sprayers
      does not currently form part of the risk assessment process. A measure of the
      ease with which residues may be transferred from the sprayer surface to the
      operator would enhance the accuracy of any such assessment. This study quantified
      the dislodgeability of six pesticides from sprayer surfaces in order to calculate
      the transfer efficiencies. The transfer efficiency was compound dependent,
      ranging from 80% for azoxystrobin to <25% for flusilazole and tebuconazole. When
      the washed and unwashed surfaces were analysed separately, more pendimethalin and
      isoproturon residues were removed from the wet surface compared with the dry
      surface. The variation in results for the different compounds highlights the need
      to consider a range of compounds to form generic statements to support guidelines
      regarding operator exposure to pesticide residues on sprayers.

PMID- 16455810
TI  - Arteriolar smooth muscle Ca2+ dynamics during blood flow control in hamster cheek
      pouch.
AB  - Intracellular calcium concentration ([Ca2+]i) governs the contractile status of
      arteriolar smooth muscle cells (SMC). Although studied in vitro, little is known
      of SMC [Ca2+]i dynamics during the local control of blood flow. We tested the
      hypothesis that the rise and fall of SMC [Ca2+]i underlies arteriolar
      constriction and dilation in vivo. Aparenchymal segments of second-order
      arterioles (diameter 35 +/- 2 microm) were prepared in the superfused cheek pouch
      of anesthetized hamsters (n = 18) and perifused with the ratiometric dye fura PE
      3 (AM) to load SMC (1 microM, 20 min). Resting SMC [Ca2+]i was 406 +/- 37 nM.
      Elevating superfusate O2 from 0 to 21% produced constriction (11 +/- 2 microm)
      that was unaffected by dye loading; [Ca2+]i increased by 108 +/- 53 nM (n = 6, P
      < 0.05). Cycling of [Ca2+]i during vasomotion (amplitude, 150 +/- 53 nM; n = 4)
      preceded corresponding diameter changes (7 +/- 1 microm) by approximately 2 s.
      Microiontophoresis (1 microm pipette tip; 1 microA, 1 s) of phenylephrine (PE)
      transiently increased [Ca2+]i by 479 +/- 64 nM (n = 8, P < 0.05) with
      constriction (26 +/- 3 microm). Flushing blood from the lumen with saline
      increased fluorescence at 510 nm by approximately 45% during excitation at both
      340 and 380 nm with no difference in resting [Ca2+]i, diameter or respective
      responses to PE (n = 7). Acetylcholine microiontophoresis (1 microA, 1 s)
      transiently reduced resting SMC [Ca2+]i by 131 +/- 21 nM (n = 6, P < 0.05) with
      vasodilation (17 +/- 1 microm). Superfusion of sodium nitroprusside (10 microM)
      transiently reduced SMC [Ca2+]i by 124 +/- 18 nM (n = 6, P < 0.05), whereas
      dilation (23 +/- 5 microm) was sustained. Resolution of arteriolar SMC [Ca2+]i in
      vivo discriminates key signaling events that govern the local control of tissue
      blood flow.

PMID- 16455811
TI  - Calf muscle-tendon properties and postural balance in old age.
AB  - We tested the hypothesis that compromised postural balance in older subjects is
      associated with changes in calf muscle-tendon physiological and mechanical
      properties. Trial duration and center of pressure (COP) displacements were
      measured in 24 younger (aged 24+/-1 yr), 10 middle-aged (aged 46+/-1 yr), and 36
      older (aged 68+/-1 yr) healthy subjects under varying levels of postural
      difficulty. Muscle-tendon characteristics were assessed by dynamometry, twitch
      superimposition, and ultrasonography. In tandem and single-leg stances, trial
      duration decreased (<or=65% lower, P<0.001) and COP displacements increased
      (<or=90% higher, P<0.05) with age. Muscle strength, size, activation capacity,
      and tendon mechanical properties decreased with age by 55, 13, 13, and 36-48%,
      respectively (P<0.05). Regressions with these parameters and balance indexes were
      significant (P<0.05) for single-leg and tandem (0.69<r2<0.90) postures only,
      indicating that the age-related changes in muscle-tendon characteristics may
      explain the majority of the variance in balance performance during tasks more
      difficult than habitual bipedal stance.

PMID- 16455812
TI  - Snoring-related energy transmission to the carotid artery in rabbits.
AB  - Epidemiological studies link habitual snoring and stroke, but mechanisms involved
      are poorly understood. One previously advanced hypothesis is that transmitted
      snoring vibration energy may promote carotid atheromatous plaque formation or
      rupture. To test whether vibration energy is present in carotid artery walls
      during snoring we developed an animal model in which we examined induced snoring
      (IS)-associated tissue energy levels. In six male, supine, anesthetized,
      spontaneously breathing New Zealand White rabbits, we surgically inserted
      pressure transducer-tipped catheters (Millar) to monitor tissue pressure at the
      carotid artery bifurcation (PCT) and within the carotid sinus lumen (PCS; artery
      ligated). Snoring was induced via external compression (sandbag) over the
      pharyngeal region. Data were analyzed using power spectral analysis for frequency
      bands above and below 50 Hz. For frequencies below 50 Hz, PCT energy was 2.2 (1.1
      12.3) cmH2O2 [median (interquartile range)] during tidal breathing (TB)
      increasing to 39.0 (2.5-95.0) cmH2O2 during IS (P = 0.05, Wilcoxon's signed-rank
      test). For frequencies > 50 Hz, PCT energy increased from 9.2 (8.3-10.4) x 10(-4)
      cmH2O2 during TB to 172.0 (118.0-569.0) x 10(-4) cmH2O2 during IS (P = 0.03).
      Concurrently, PCS energy was 13.4 (8.5-18.0) x 10(-4) cmH2O2 during TB and 151.0
      (78.2-278.8) x 10(-4) cmH2O2 during IS (P < 0.03). The PCS energy was greater
      than PCT energy for the 100-275 Hz bandwidth. In conclusion, during IS there is
      increased energy around and within the carotid artery, including lower frequency
      amplification for PCS. These findings may have implications for carotid
      atherogenesis and/or plaque rupture.

PMID- 16455813
TI  - Prostaglandin involvement in lung C-fiber activation by substance P in guinea
      pigs.
AB  - Airway hyperresponsiveness is a cardinal feature of asthma. Lung C-fiber
      activation induces central and local defense reflexes that may contribute to
      airway hyperresponsiveness. Initial studies show that substance P (SP) activates
      C fibers even though it is produced and released by these same C fibers. SP may
      induce release of other endogenous mediators. Bradykinin (BK) is an endogenous
      mediator that activates C fibers. The hypothesis was tested that SP activates C
      fibers via BK release. Guinea pigs were anesthetized, and C-fiber activity (FA),
      pulmonary insufflation pressure (PIP), heart rate, and arterial blood pressure
      were monitored before and after intravenous injection of capsaicin (Cap), SP, and
      BK. Identical agonist challenges were repeated after infusion of an antagonist
      cocktail of des-Arg9-[Leu8]-BK (10(-3) M, B1 antagonist), and HOE-140 (10(-4) M,
      B2 antagonist). After antagonist administration, BK increased neither PIP nor FA.
      Increases in neither PIP nor FA were attenuated after Cap or SP challenge. In a
      second series of experiments, Cap and SP were injected before and after infusion
      of indomethacin (1 mg/kg iv) to determine whether either agent activates C fibers
      through release of arachidonic acid metabolites. Indomethacin administration
      decreased the effect of SP challenge on FA but not PIP. The effect of Cap on FA
      or PIP was not altered by indomethacin. In subsequent experiments, C fibers were
      activated by prostaglandin E2 and F2alpha. Therefore, exogenously applied SP
      stimulates an indomethacin-sensitive pathway leading to C-fiber activation.

PMID- 16455814
TI  - Sildenafil improves cardiac output and exercise performance during acute hypoxia,
      but not normoxia.
AB  - Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments
      of hypoxia-induced pulmonary hypertension on exercise performance at altitude.
      The purpose of this study was to determine the effects of sildenafil during
      normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no
      significant effects on normoxic exercise, and 2) sildenafil would improve cardiac
      output, arterial oxygen saturation (SaO2), and performance during hypoxic
      exercise. Ten trained men performed one practice and three experimental trials at
      sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test
      consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA)
      followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules
      (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly
      counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8%
      oxygen) 1 h before exercise. At SL, sildenafil had no effects on any
      cardiovascular or performance measures. At HA, sildenafil increased stroke volume
      (measured by impedance cardiography), cardiac output, and SaO2 during set-work
      rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was
      also higher during the time trial (P<0.05) in response to sildenafil, despite
      higher work rates. Post hoc analyses revealed two subject groups, sildenafil
      responders and nonresponders, who improved time-trial performance by 39% (P<0.05)
      and 1.0%, respectively. No dose-response effects were observed. During cycling
      exercise in acute hypoxia, sildenafil can greatly improve cardiovascular
      function, SaO2, and performance for certain individuals.

PMID- 16455815
TI  - Point:Counterpoint: The parafacial respiratory group (pFRG)/pre-Botzinger complex
      (preBotC) is the primary site of respiratory rhythm generation in the mammal.
      Point: the PFRG is the primary site of respiratory rhythm generation in the
      mammal.

PMID- 16455816
TI  - Androgen activation of the sterol regulatory element-binding protein pathway:
      Current insights.
AB  - The cellular effects of androgens are mediated by a cognate receptor, the
      androgen receptor. Typically, the androgen receptor is viewed to exert its
      activity by binding to androgen response elements located in or near the promoter
      region of target genes, thereby directly affecting the expression of these genes.
      However, increasing evidence indicates that androgens may also indirectly
      influence the expression of genes that do not contain androgen response elements
      by modulating the activity of secondary transcription factors, mediating the
      expression of growth factors acting in a paracrine or autocrine fashion, or by
      inducing changes in the production of other hormones. These indirect effects of
      androgens can induce cascade-like actions and may play an important role in more
      complex processes involving coordinated responses of genes, cells, and organs.
      Previously, our laboratory has identified and characterized a novel indirect
      mechanism of androgen action involving proteolytical activation of the key
      lipogenic transcription factor sterol regulatory element-binding protein (SREBP),
      resulting in the coordinate up-regulation of entire cellular lipogenic pathways.
      Interestingly, activation of SREBPs by androgens occurs not only under normal
      physiological conditions but has also been observed in a growing number of
      pathologies, and more in particular in the setting of steroid-regulated cancers,
      where increased lipogenesis has been shown to have remarkable diagnostic and
      prognostic potential and is considered a prime target for novel therapeutic
      approaches. This review aims to analyze current insights into the molecular
      mechanism(s) underlying androgen activation of the SREBP pathway and to ascertain
      the extent to which this phenomenon can be generalized to androgen-responsive
      cell systems.

PMID- 16455817
TI  - Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal
      cumulus cells express neuronal and immune-related genes: does this expand their
      role in the ovulation process?
AB  - Ovulation is a complex process initiated by the preovulatory LH surge,
      characterized by cumulus oocyte complex (COC) expansion and completed by the
      release of a mature oocyte. Although many ovarian genes that impact ovulation
      have been identified, we hypothesized that genes selectively expressed in COCs
      would be overlooked by approaches using whole ovary or granulosa cell samples.
      RNA isolated from COCs collected from preovulatory follicles of equine chorionic
      gonadotropin (CG) primed mice and at selected times after human CG treatment was
      subjected to microarray analyses and results confirmed by RT-PCR analyses,
      Western blotting, and immunofluorescent studies. A remarkable number of genes
      were up-regulated in COCs including Areg, Ereg, and Btc. Several genes
      selectively expressed in cumulus cells compared with granulosa cells were related
      to neuronal (Mbp, Tnc, Nts) or immune (Alcam, Pdcd1, Cd34, Cd52, and Cxcr4) cell
      function. In addition to Sfrp2, other members of the Wnt/Fzd family (Sfrp4, Fdz1
      and Fdz2) were expressed in COCs. Thus, there is a cumulus cell-specific,
      terminal differentiation process. Furthermore, immunofluorescent analyses
      documented that cumulus cells are highly mitotic for 4-8 h after human CG and
      then cease dividing in association with reduced levels of Ccnd2 mRNA. Other down
      regulated genes included: Cyp19a1, Fshr, Inhb, and the oocyte factors Zp1-3 and
      Gja4. In summary, the vast number of matrix, neuronal, and especially immune cell
      related genes identified by the gene- profiling data of COCs constitutes strong
      and novel evidence that cumulus cells possess a repertoire of immune functions
      that could be far greater than simply mediating an inflammatory-like response.

PMID- 16455818
TI  - A novel cytochrome P450, zebrafish Cyp26D1, is involved in metabolism of all
      trans retinoic acid.
AB  - Retinoid signaling is essential for development of vertebrate embryos, and its
      action is mainly through retinoic acid (RA) binding to its RA receptors and
      retinoid-X receptors, while the critical concentration and localization of RA in
      embryos are determined by the presence and activity of retinal dehydrogenases
      (for RA synthesis) and cytochrome P450 RAs (Cyp26s) (for degradation of RA).
      Previously, we identified a novel cyp26 gene (cyp26d1) in zebrafish that is
      expressed in hindbrain during early development. Using reverse-phase HPLC
      analyses, we show here that zebrafish Cyp26D1 expressed in 293T cells could
      metabolize all-trans RA, 9-cis RA, and 13-cis RA, but could not metabolize
      retinol or retinal. The metabolites of all-trans RA produced by Cyp26D1 were the
      same as that produced by Cyp26A1, which are mainly 4-hydroxy-all-trans-RA and 4
      oxo-all-trans-RA. Performing mRNA microinjection into zebrafish embryos, we
      demonstrated that overexpression of Cyp26D1 in embryos not only caused the
      distance between rhombomere 5 and the first somite of the injected embryos to be
      shorter than control embryos but also resulted in left-right asymmetry of
      somitogenesis in the injected embryos. These alterations were similar to those
      caused by the overexpression of cyp26a1 in zebrafish embryos and to that which
      resulted from treating embryos with 1 microm 4-diethylamino-benzaldehyde (retinal
      dehydrogenase inhibitor), implying that cyp26d1 can antagonize RA activity in
      vivo. Together, our in vitro and in vivo results provided direct evidence that
      zebrafish Cyp26D1 is involved in RA metabolism.

PMID- 16455819
TI  - Activation function-1 domain of estrogen receptor regulates the agonistic and
      antagonistic actions of tamoxifen.
AB  - The antiestrogen tamoxifen has been widely used for decades as selective estrogen
      receptor (ER) modulator for ERalpha-positive breast tumors. Tamoxifen
      significantly reduces tumor recurrence by binding to the activation function-2
      (AF-2) domain of the ER. Acquired resistance to tamoxifen in breast cancer
      patients is a serious therapeutic problem. Antiestrogen-resistant breast cancer
      often shows increased expression of the epidermal growth factor receptor (EGFR)
      family members, EGFR and ErbB2. In this report we now show that overexpression of
      EGFR or activated AKT-2 in MCF-7 cells leads to phosphorylation of Ser167 in the
      AF-1 domain of ERalpha, enhanced ER-amplified in breast cancer 1 (ER:AIB1)
      interaction in the presence of tamoxifen, and resistance to tamoxifen. In
      contrast, transfection of activated MAPK kinase, an immediate upstream activator
      of MAPK (ERK 1 and 2) into MCF-7 cells leads to phosphorylation of Ser118 in the
      AF-1 domain of ERalpha, inhibition of ER-amplified in breast cancer 1 (ER:AIB1)
      interaction in the presence of Tam, and maintenance of sensitivity to tamoxifen.
      Inhibition of AKT by short inhibitory RNA blocked Ser167 phosphorylation in ER
      and restored tamoxifen sensitivity. However, maximum sensitivity to tamoxifen was
      observed when both AKT and MAPK were inhibited. Taken together, these data
      demonstrate that different phosphorylation sites in the AF-1 domain of ERalpha
      regulate the agonistic and antagonistic actions of tamoxifen in human breast
      cancer cells.

PMID- 16455820
TI  - The CCAAT enhancer-binding protein-alpha negatively regulates the transactivation
      of androgen receptor in prostate cancer cells.
AB  - The basic leucine zipper transcription factor, CCAAT enhancer-binding protein
      alpha (C/EBPalpha), negatively regulates cell proliferation and induces terminal
      differentiation of various cell types. C/EBPalpha is expressed in the prostate,
      but its potential role in the tissue is unknown. Herein, we show that C/EBPalpha
      is highly expressed at the stage of growth arrest during prostate development.
      Furthermore, overexpression of C/EBPalpha decreases the rate of DNA synthesis in
      LNCaP prostate cancer cells. Investigation of the potential cross-talk between
      C/EBPalpha and androgen receptor (AR) that is responsible for androgen-dependent
      prostate proliferation demonstrates that androgen-dependent transactivation of AR
      is strongly repressed by C/EBPalpha. C/EBPalpha directly binds AR in vitro and
      forms a complex with AR in vivo. C/EBPalpha neither prevents the nuclear
      translocation of AR nor disrupts the N/C-terminal interaction of AR, which are
      both necessary for its proper transactivation activity upon ligand binding. To
      modulate AR transactivation, however, C/EBPalpha does compete with AR
      coactivators for AR binding. Additionally, C/EBPalpha is recruited onto AR-target
      promoters with AR and is further able to inhibit the expression of endogenous
      prostate-specific antigen in prostate cancer cells. Our results suggest
      C/EBPalpha as a potent AR corepressor and provide insight into the role of
      C/EBPalpha in prostate development and cancer.

PMID- 16455821
TI  - A controlled trial of a school-based intervention to improve asthma management.
AB  - The present study investigated schools as an appropriate context for an
      intervention designed to produce clinical and psychological benefits for children
      with asthma. A total of 193 out of 219 (88.1%) children with asthma (aged 7-9
      yrs) from 23 out of 24 (95.8%) schools completed the study. Intervention schools
      received a staff asthma-training session, advice on asthma policy, an emergency
      beta2-agonist inhaler with spacer and whole-class asthma workshops.
      Nonintervention schools received no asthma-related input. Intervention children
      required less general practitioner-prescribed preventer medication despite no
      differences in symptom control compared with the nonintervention asthmatic group.
      Increased peer knowledge of asthma may have mediated improved active quality of
      life in the intervention group, together with increased self-esteem in young
      females. Those females not receiving the intervention, but identified as being
      asthmatic within the classroom, and thus possibly stigmatised, reported decreased
      self-esteem. Lower self-esteem in young males was associated with pet ownership.
      No change was found in staff knowledge, the establishment of asthma policies or
      school absences which were low even before intervention. In conclusion, a whole
      school intervention can improve the health of children with asthma when followed
      with support for all children but effects are likely to be modified by sex and
      the home environment.

PMID- 16455822
TI  - Should forced expiratory volume in six seconds replace forced vital capacity to
      detect airway obstruction?
AB  - It has been suggested that forced expiratory volume in six seconds (FEV(6))
      should be substituted for forced vital capacity (FVC) to measure fractions of
      timed expired volume for airflow obstruction detection. The present authors
      hypothesised that this recommendation might be questionable because flow after 6
      s of forced expiration from more diseased lung units with the longest time
      constants was most meaningful and should not be ignored. Furthermore, previous
      studies comparing FEV(6) and FVC included few subjects with mild or no disease.
      The present study used spirometric data from the USA Third National Health and
      Nutrition Evaluation Survey with prior published ethnicity- and sex-specific
      equations for FEV(1)/FEV(6), FEV(1)/FVC and FEV(3)/FVC, and new equations for
      FEV(3)/FEV(6), all derived from approximately 4,000 adult never-smokers aged 20
      80 yrs. At 95% confidence intervals, 21.3% of 3,515 smokers and 41.3% of smokers
      aged >51 yrs had airway obstruction; when comparing FEV(1)/FEV(6) with
      FEV(1)/FVC, 13.5% were concurrently abnormal, 1.5% were false positives and 4.1%
      were false negatives; and when comparing FEV(3)/FEV(6) with FEV(3)/FVC, 11.6%
      were concurrently abnormal, 3.3% were false positives and 5.7% were false
      negatives. Substituting forced expiratory volume in six seconds for forced vital
      capacity to determine the fractional rates of exhaled volumes reduces the
      sensitivity of spirometry to detect airflow obstruction, especially in older
      individuals and those with lesser obstruction.

PMID- 16455823
TI  - Sniff nasal inspiratory pressure: what is the optimal number of sniffs?
AB  - Sniff nasal inspiratory pressure (SNIP) measurement is a volitional noninvasive
      assessment of inspiratory muscle strength. A maximum of 10 sniffs is generally
      used. The purpose of the present study was to investigate whether the maximum
      SNIP improved after the tenth sniff. In total, 20 healthy volunteers and 305
      patients with various neuromuscular and lung diseases were encouraged to perform
      40 and 20 sniffs, respectively. The best SNIP among the first 10 sniffs was lower
      than the best SNIP among the next 10 sniffs in the healthy volunteers and
      patients. The SNIP improvement after the twentieth sniff was marginal. In
      conclusion, a learning effect persists after the tenth sniff. The current authors
      suggest using 10 additional sniffs when the best result of the first 10 sniffs is
      slightly below normal, or when sniff nasal inspiratory pressure is used to
      monitor a progressive decline in inspiratory muscle strength.

PMID- 16455824
TI  - Impact of initial antibiotic choice on mortality from pneumococcal pneumonia.
AB  - To determine the impact of initial antimicrobial choice on 30-day mortality rate
      in patients with community-acquired pneumonia due to Streptococcus pneumoniae
      (CAP-SP), a prospective, observational study was conducted in 35 Spanish
      hospitals. A total of 638 patients with CAP-SP were identified. Antimicrobials
      were chosen by the attending physician. Patients were grouped into the following
      categories: beta-lactam monotherapy (n = 251), macrolide monotherapy (n = 37),
      beta-lactam plus macrolide (n = 198), levofloxacin alone/combination (n = 48),
      and other combinations (n = 104). The reference category was beta
      lactam+macrolide. The 30-day survival probability was 84.9%. Using multivariate
      survival analysis, factors related to mortality in the entire population were:
      bilateral disease, suspected aspiration, shock, HIV infection, renal failure and
      pneumonia severity index (PSI) score Class IV versus I-III and categories V
      versus I-III. The association of beta-lactams+macrolides was not better than the
      use of beta-lactams alone. The current authors analysed the different groups of
      patients with significant mortality/morbidity: intensive care unit, PSI Class
      >III, renal failure, chronic lung disease and bacteraemia. Only in patients with
      PSI Class >III, who had undergone initial antimicrobial choice classified as
      other combinations, were associated with higher mortality. In conclusion, the
      current authors have not demonstrated an independent association between initial
      antimicrobial regimen and 30-day mortality in community-acquired pneumococcal
      pneumonia patients, except for those with a higher pneumonia severity index
      score.

PMID- 16455825
TI  - Combined transbronchial needle aspiration and positron emission tomography for
      mediastinal staging of NSCLC.
AB  - There are no data available combining transbronchial needle aspiration (TBNA) of
      mediastinal lymph nodes and positron emission tomography (PET) in the staging of
      nonsmall cell lung cancer (NSCLC). The aim of the current study was to determine
      if these two methods can enhance the negative predictive value of the individual
      modality alone, for a specific lymph node station, and if this integrated
      approach can reduce the number of mediastinoscopies. A total of 113 patients with
      enlarged mediastinal lymph nodes (> or = 1 cm), who underwent both TBNA and PET
      scanning, were included. In 51 patients, histopathology, confirmed by surgical
      lymph node dissection, was compared with PET results and TBNA. Sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy to
      detect malignant lymphadenopathy was 68 (13/19), 89 (119/134), 46 (13/28), 95
      (119/125) and 86% (132/152) for PET, respectively; 54% (6/11), 100 (53/53), 100
      (6/6), 91 (53/58) and 92% (59/64), respectively for TBNA; and 100 (11/11), 94
      (50/53), 79 (11/14), 100 (50/50) and 95 (61/64) for combined TBNA and PET,
      respectively. Combination of transbronchial needle aspiration and positron
      emission tomography has the potential to allow adequate mediastinal staging of
      nonsmall cell lung cancer with enlarged lymph nodes in most patients without the
      need for mediastinoscopy.

PMID- 16455826
TI  - Telomerase activation in a model of lung adenocarcinoma.
AB  - Ovine pulmonary adenocarcinoma (OPA) is a lung cancer strikingly similar to the
      pneumonic-type mixed invasive adenocarcinoma with a predominant
      bronchioloalveolar component in humans. Telomerase activity in OPA and the
      potential involvement of the kinase Akt in telomerase activation and regulation
      of cell proliferation were investigated. Lung tissues were collected from sheep
      with a histopathological diagnosis of OPA or controls. Epithelial cell cultures
      were derived in vitro from lung tissues. Telomerase activity was evaluated using
      the telomeric repeat amplification protocol method. Phosphorylation of Akt was
      detected by Western blotting. Telomerase activity was significantly higher in OPA
      lung tissues compared to control lung tissues. A high telomerase activity was
      detected in eight out of 12 (67%) primary cell cultures derived from tumours. A
      high level of expression of phosphorylated Akt was found in 10 out of 27 (37%)
      tumours, with abolition of Akt activation in response to epidermal growth factor
      stimulation demonstrated in primary cell cultures derived from tumours.
      Telomerase activation takes place in ovine pulmonary adenocarcinoma tumour cells
      and may be partly attributable to Akt activation. Telomerase may inhibit cellular
      senescence and contribute to the accumulation of tumour cells in mixed
      adenocarcinoma with a bronchioloalveolar component. Further work is necessary to
      identify alternative signalling pathways of telomerase activation in tumours.

PMID- 16455827
TI  - Effects of macrolides on pneumolysin of macrolide-resistant Streptococcus
      pneumoniae.
AB  - To clarify the discrepancy between increasing resistance and conservative
      clinical effects of macrolides on macrolide-resistant Streptococcus pneumoniae,
      the authors evaluated the effects of sub-minimum inhibitory concentrations of
      macrolides on pneumolysin. In vitro, S. pneumoniae was incubated with 1, 2 and 4
      microg.mL(-1) of clarithromycin (CLR) and azithromycin (AZM) for 8 h. Western
      blot analysis and haemolytic assay were performed to examine the production and
      activities of pneumolysin. In vivo, mice were infected with S. pneumoniae intra
      nasally and treated with CLR (40 or 200 mg.kg(-1) twice daily) or AZM (40 or 200
      mg.kg(-1) once daily) orally for 7 days. After 72 h post-infection, western blot
      analysis was performed to examine pneumolysin production in lungs. Survival rates
      were observed for 10 days. In vitro, every concentration of macrolide inhibited
      pneumolysin production more than the control. CLR (2 and 4 microg.mL(-1)) and AZM
      (4 microg.mL(-1)) reduced the pneumolysin activities more than the control. In
      vivo, macrolides (200 mg.kg(-1)) reduced pneumolysin in murine lungs more than
      the control. CLR (40 and 200 mg.kg(-1)) and AZM (200 mg.kg(-1)) improved the
      survival rates more than the control. The study results show that sub-minimum
      inhibitory concentrations of macrolides reduced pneumolysin. This might be
      related to the effectiveness of macrolides against pneumonia caused by high-level
      macrolide-resistant Streptococcus pneumoniae. Further investigations are
      necessary to evaluate the effects of macrolides on macrolide-resistant
      Streptococcus pneumoniae.

PMID- 16455828
TI  - Angiotensin-converting enzyme inhibitor use and pneumonia risk in a general
      population.
AB  - The aim of the present study was to assess whether the use of angiotensin
      converting enzyme (ACE) inhibitors is associated with a decreased risk of
      hospitalisation for community-acquired pneumonia (CAP) in a general, essentially
      white population. Data were obtained from the Dutch PHARMO Record Linkage System.
      Cases were defined as patients with a first hospital admission for CAP. For each
      case, up to four population controls were matched by age and sex. The study
      population comprised 1,108 patients with a first hospital admission for CAP and
      3,817 matched controls. After adjusting for several confounders, ACE inhibitor
      use was not associated with a decreased incidence of pneumonia (adjusted odds
      ratio (OR) 1.12; 95% confidence interval (CI) 0.88-1.43). Additionally, no
      significant association was observed in patients with diabetes, respiratory
      diseases, heart failure, or patients with both of the last two conditions.
      Furthermore, adjustment of treatment effects on pneumonia risk using
      stratification on balancing score also showed no significant association between
      ACE inhibitor use and pneumonia risk within the different strata (overall
      adjusted OR 1.09; 95% CI 0.87-1.36). In contrast with previous findings in Asian
      populations, the current authors were not able to confirm the beneficial effect
      of angiotensin-converting enzyme inhibitors on pneumonia risk in a general,
      essentially white population.

PMID- 16455829
TI  - C-reactive protein levels and clinically important predictive outcomes in stable
      COPD patients.
AB  - The aim of this study was to determine the relationship between C-reactive
      protein (CRP) levels and factors known to predict outcome in stable chronic
      obstructive pulmonary disease (COPD) patients. The following were studied in 130
      stable COPD patients: spirometry, lung volume, arterial oxygen tension (P(a,O2)),
      dyspnoea, 6-min walk distance (6MWD), body mass index, fat-free mass index, BODE
      (body mass index, obstruction, dyspnoea and exercise capacity), health-related
      quality of life, smoking status, the presence of cardiovascular risk factors or
      disease, corticosteroid use and number of exacerbations in the previous year. CRP
      levels were measured in these patients and in 65 controls. Using univariate and
      multivariate analyses, any possible association with the predictors of outcomes
      was evaluated. CRP levels were higher in COPD patients than in controls (4.1
      versus 1.8 mg.L(-1), respectively). Correlation was found with the following
      variables: forced expiratory volume in one second (FEV1; -0.23), FEV1 % (-0.20),
      forced vital capacity (FVC; -0.24), FVC % (-0.24), Global Initiative for Chronic
      Obstructive Lung Disease stage (0.17), BODE (0.17), inspiratory capacity/total
      lung capacity (-0.20), P(a,O2) (-0.40) and 6MWD (-0.30). Using multivariate
      analysis, P(a,O2) and 6MWD manifested the strongest negative association with CRP
      levels. C-reactive protein levels in stable chronic obstructive pulmonary disease
      patients are best correlated with arterial oxygen tension and 6-min walk
      distance. This should be considered when C-reactive protein levels are measured
      in stable chronic obstructive pulmonary disease patients.

PMID- 16455830
TI  - Role of macrophage migration inhibitory factor in ovalbumin-induced airway
      inflammation in rats.
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that
      reportedly counteracts the anti-inflammatory effect of endogenous
      glucocorticoids. There have only been a few reports that demonstrate a potential
      link between MIF and bronchial asthma. In an attempt to further clarify the
      precise role of MIF in asthma, the present authors examined the effect of anti
      MIF antibody (Ab) on airway inflammation and airway hyperresponsiveness in an
      ovalbumin-immunised rat asthma model. Actively immunised Brown Norway rats
      received ovalbumin inhalation with or without treatment of anti-MIF Ab. The
      levels of MIF in bronchoalveolar lavage fluid were significantly elevated after
      the ovalbumin challenge. An immunohistochemical study revealed positive
      immunostaining for MIF in bronchial epithelium, even in nonsensitised rats, and
      the MIF staining in bronchial epithelium was enhanced after the ovalbumin
      challenge. Anti-MIF Ab significantly decreased the number of total cells,
      neutrophils and eosinophils in the bronchoalveolar lavage fluid of the ovalbumin
      challenged rats, and also attenuated the ovalbumin-induced airway
      hyperresponsiveness to ovalbumin and methacholine. However, anti-MIF Ab did not
      affect the level of serum ovalbumin-specific IgE, suggesting that anti-MIF Ab did
      not suppress immunisation itself. The results indicate that macrophage migration
      inhibitory factor plays a crucial role in airway inflammation and airway
      hyperresponsiveness in asthma.

PMID- 16455831
TI  - Comparison of asthma treatment given in addition to inhaled corticosteroids on
      airway inflammation and responsiveness.
AB  - There is increasing evidence that the assessment of eosinophilic airway
      inflammation using induced sputum and measurement of airway hyperresponsiveness
      provides additional, clinically important information concerning asthma control.
      The aim of this study was to directly compare the effects of different treatments
      on these markers in patients with asthma and persistent symptoms, despite the use
      of low-dose inhaled corticosteroids. A double-blind four-way crossover study was
      performed, which compared a 1-month treatment with budesonide 400 mug b.i.d.,
      additional formoterol, additional montelukast and placebo in 49 patients with
      uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment
      separated by a 4-week washout period. The change in sputum eosinophil count with
      formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI)
      0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold
      reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold
      reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from
      placebo. The changes in methacholine airway responsiveness were small and did not
      differ between treatments. High-dose budesonide had the broadest range of
      beneficial effects on other outcomes, including symptom scores, morning peak
      expiratory flow and forced expiratory volume in one second. In conclusion,
      treatment given in addition to low-dose inhaled corticosteroids results in modest
      benefits. Formoterol and high-dose budesonide have contrasting effects on
      eosinophilic airway inflammation.

PMID- 16455832
TI  - Low levels of air pollution induce changes of lung function in a panel of
      schoolchildren.
AB  - In search of sensitive screening parameters for assessing acute effects of
      ambient air pollutants in young schoolchildren, the impact of 8-h average air
      pollution before lung function testing was investigated by oscillatory
      measurements of resistance and spirometry with flow-volume loops. At a central
      elementary school in Linz, the capital of Upper Austria, 163 children aged 7-10
      yrs underwent repeated examinations at the same time of day during 1 school year,
      yielding a total of 11-12 lung function tests per child. Associations to mass
      concentrations of particulate matter and nitrogen dioxide (NO(2)) measured
      continuously at a nearby monitoring station were tested, applying the Generalised
      Estimating Equations model. Reductions per 10 microg.m(-3) (both for particles
      and for NO(2)) were in the magnitude of 1% for most lung function parameters. The
      most sensitive indicator for acute effects of combustion-related pollutants was a
      change in maximal expiratory flow in small airways. NO(2) at concentrations below
      current standards reduced (in the multipollutant model) the forced expiratory
      volume in one second by 1.01%, maximal instantaneous forced flow when 50% of the
      forced vital capacity remains to be exhaled (MEF(50%)) by 1.99% and MEF(25%) by
      1.96%. Peripheral resistance increased by 1.03% per 10 microg.m(-3) of
      particulate matter with a 50% cut-off aerodynamic diameter of 2.5 mum (PM(2.5)).
      Resistance is less influenced by the child's cooperation and should be utilised
      more often in environmental epidemiology when screening for early signs of small
      airway dysfunction from urban air pollution, but cannot replace the measurement
      of MEF(50%) and MEF(25%). In the basic model, the reduction of these parameters
      per 10 microg.m(-3) was highest for NO(2), followed by PM(1), PM(2.5) and PM(10),
      while exposure to coarse dust (PM(10)-PM(2.5)) did not change end-expiratory flow
      significantly. All acute effects of urban air pollution found on the lung
      function of healthy pupils were evident at levels below current European limit
      values for nitrogen dioxide. Thus, planned reduction of nitrogen dioxide emission
      (Euro 5; vehicles that comply with the emission limits as defined in Directive
      99/96/EC) of 20% in 2010 would seem to be insufficient.

PMID- 16455833
TI  - Volatile organic compounds in the exhaled breath of young patients with cystic
      fibrosis.
AB  - Inflammatory mediators in the exhaled breath are receiving growing medical
      interest as noninvasive disease markers. Volatile organic compounds have been
      investigated in this context, but clinical information and methodological
      standards are limited. The levels of ethane, propane, n-pentane, methanol,
      ethanol, 2-propanol, acetone, isoprene, benzene, toluene, dimethyl sulphide (DMS)
      and limonene were measured in repeated breath samples from 20 cystic fibrosis
      patients and 20 healthy controls (aged 8-29 yrs). Three end-exhaled and one
      ambient air sample were collected per person and analysed on a customised gas
      chromatography system. Intra-subject coefficients of variation ranged between 9
      and 34%, and hydrocarbon breath levels were influenced by their inspired
      concentrations. The alveolar gradient for pentane was higher in cystic fibrosis
      patients than in healthy controls (0.36 versus 0.21 ppb) and inversely
      proportional to forced expiratory volume in one second; highest values were
      observed in patients with pulmonary exacerbations (0.73 versus 0.24 ppb). Cystic
      fibrosis patients also exhibited a lower output of DMS (3.9 versus 7.6 ppb).
      Group differences were not significant for ethane and the remaining substances.
      It was concluded that chemical breath analysis for volatile organic compounds is
      feasible and may hold potential for the noninvasive diagnosis and follow-up of
      inflammatory processes in cystic fibrosis lung disease.

PMID- 16455834
TI  - Physiological effects of vibration in subjects with cystic fibrosis.
AB  - The physiological mechanisms by which vibration and other physiotherapy
      interventions may clear secretions in subjects with cystic fibrosis are unknown.
      The main aim of this study was to compare the expiratory flow rates and
      frequencies of airflow oscillation of vibration to those of Acapella(R),
      Flutter(R), positive expiratory pressure and percussion. Respiratory flow rates
      were measured during interventions, the order of which was randomised. The
      oscillation of the airflow of the interventions was determined by frequency
      spectral analysis. In 18 young adult subjects with cystic fibrosis, the mean peak
      expiratory flow rate of vibration was greater than Flutter(R), percussion,
      Acapella(R) and positive expiratory pressure. The mean+/-sd of the oscillation of
      the airflow of vibration (8.4+/-0.4 Hz) was lower than Acapella(R) (13.5+/-1.7
      Hz) and Flutter(R) (11.3+/-1.5 Hz) but similar to percussion (7.3+/-0.3 Hz).
      Theoretically, the higher peak expiratory flow rate of vibration compared to the
      other physiotherapy interventions may promote secretion clearance. In addition,
      the frequency of oscillation of vibration was within the range demonstrated to
      increase mucus transport. This study has provided some evidence for the
      physiological rationale for the use of vibration to aid secretion clearance.

PMID- 16455835
TI  - Continuous positive airway pressure does not reduce blood pressure in nonsleepy
      hypertensive OSA patients.
AB  - Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity
      and mortality. Several randomised controlled trials have shown that continuous
      positive airway pressure (CPAP) treatment of OSA reduces blood pressure (BP).
      This randomised, sham-placebo controlled crossover trial assesses whether CPAP
      produces a similar clinically significant fall in BP in hypertensive OSA
      patients, but without hypersomnolence. Thirty-five, nonsleepy, hypertensive
      patients with OSA were treated with CPAP for 1 month, randomised first to either
      therapeutic or sham-placebo (subtherapeutic CPAP, about 1 cmH(2)O pressure). The
      second months' alternative treatment followed a 2-week washout period. BP was
      measured over 24 h, before and at the end of the two treatment periods: mean 24-h
      BP was the primary outcome variable. There was no overall significant difference
      in mean 24-h BP: the change in mean 24-h BP on therapeutic CPAP was -2.1 mmHg (sd
      8.1), and -1.1 mmHg (sd 8.1) on subtherapeutic CPAP, with a difference of 0.7
      mmHg (95% confidence interval (CI) +2.9- -4.4). There was a small significant
      fall in Epworth Sleepiness Score, therapeutic (-1.4) versus sham (-0.3), and
      difference -1.2 (95% CI -2.0- -0.4), but no change in objective sleepiness. In
      nonhypersomnolent hypertensive patients with obstructive sleep apnoea, there is
      no significant fall in mean 24-h blood pressure with continuous positive airway
      pressure, in contrast to the fall seen in hypersomnolent patients with
      obstructive sleep apnoea.

PMID- 16455836
TI  - Airway inflammation in iron ore miners exposed to dust and diesel exhaust.
AB  - The aim of the present study was to investigate if underground miners exposed to
      dust and diesel exhaust in an iron ore mine would show signs of airway
      inflammation as reflected in induced sputum. In total, 22 miners were studied,
      once after a holiday of at least 2 weeks and the second time after 3 months of
      regular work. Control subjects were 21 "white-collar" workers. All subjects
      completed a questionnaire regarding medical and occupational history, and
      underwent lung function testing and induced sputum collection. Total and
      differential cell counts and analyses of the fluid phase of the induced sputum
      were performed. Sampling of personal exposure to elemental carbon, nitrogen
      dioxide and inhalable dust was recorded. The average concentrations of inhalable
      dust, nitrogen dioxide and elemental carbon were 3.2 mg.m-3, 0.28 mg.m-3 and 27
      microg.m-3, respectively. Miners had increased numbers of inflammatory cells,
      mainly alveolar macrophages and neutrophils, and increased concentrations of
      fibronectin, metalloproteinase-9 and interleukin-10 in induced sputum compared
      with controls. In conclusion, miners in an underground iron ore mine demonstrated
      persistent airway inflammation that was as pronounced after a 4-week holiday as
      after a 3-month period of work underground in the mine.

PMID- 16455837
TI  - New aspects of airway mechanics in pre-term infants.
AB  - High-frequency respiratory impedance data measured noninvasively by the high
      speed interrupter technique (HIT), particularly the first antiresonance frequency
      (f(ar,1)), is related to airway wall mechanics. The aim of this study was to
      evaluate the feasibility and repeatability of HIT in unsedated pre-term infants,
      and to compare values of f(ar,1) from 18 pre-term (post-conceptional age 32-37
      weeks, weight 1,730-2,910 g) and 18 full-term infants (42-47 weeks, 3,920-5,340
      g). Among the pre-term infants, there was good short-term repeatability of
      f(ar,1) within a single sleep epoch (mean (sd) coefficient of variance: 8
      (1.7)%), but 95% limits of agreement for repeated measures of f(ar,1) after 3-8 h
      were relatively wide (-41 Hz; 37 Hz). f(ar,1) was significantly lower in pre-term
      infants (199 versus 257 Hz), indicating that wave propagation characteristics in
      pre-term airways are different from those of full-term infants. The present
      authors suggest that this is consistent with developmental differences in airway
      wall structure and compliance, including the influence of the surrounding tissue.
      Since flow limitation is determined by wave propagation velocity and airway cross
      sectional area, it was hypothesised that the physical ability of the airways to
      carry large flows is fundamentally different in pre-term than in full-term
      infants.

PMID- 16455838
TI  - Formoterol Turbuhaler as reliever medication in patients with acute asthma.
AB  - The aim of this study was to compare the efficacy and safety of formoterol versus
      salbutamol as reliever medication in patients presenting at an emergency dept
      with acute asthma. A randomised, double-blind, double-dummy, parallel group study
      was performed in four Australian emergency treatment centres. The study included
      a total of 78 adult patients (mean baseline forced expiratory volume in one
      second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected
      dose equivalence of formoterol Turbuhaler 4.5 microg (delivered dose) and
      salbutamol pressurised metered-dose inhaler 200 microg (metered dose), patients
      received a total of formoterol Turbuhaler 36 microg (delivered) or salbutamol
      pressurised metered-dose inhaler with spacer 1,600 microg (metered), divided into
      two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic beta2
      agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45
      min. At 45 min, mean increases in FEV1 expressed in % pred were 6.6% and 9.3%,
      respectively, with a small adjusted mean difference in favour of salbutamol
      (3.0%, 95% confidence interval -2.0-8.0). Transient increases in systemic beta2
      agonist effects occurred predominantly with salbutamol, although no significant
      treatment differences were observed. Eight patients discontinued due to adverse
      events. In this study of patients presenting at emergency depts with acute
      asthma, formoterol Turbuhaler 36 microg was well tolerated and, as rescue
      therapy, had an efficacy that was not different from that of salbutamol
      pressurised metered-dose inhaler with spacer 1,600 microg in the number of
      patients studied.

PMID- 16455839
TI  - Regulation of human lung epithelial cell numbers by diesel exhaust particles.
AB  - Particulate air pollution is associated with respiratory morbidity and has
      cytotoxic and pro-inflammatory effects. The effects of diesel exhaust particles
      (DEP) on proliferation and apoptosis of A549 lung epithelial cells were examined.
      When deprived of serum (serum starvation), epithelial cell numbers fell, but DEP
      (5-200 microg.mL-1) prevented this. Using flow cytometric analysis of propidium
      iodide (PI) staining, DEP (10 microg.mL-1) increased cells in the S phase of cell
      cycle from 12.85 to 18.75% after 48 h, reversing serum starvation-induced G0/1
      arrest. DEP also reduced the increase in apoptotic cells, as defined by double
      expression of annexin V/PI, observed after serum starvation (from 28.35 to
      15.46%). The antioxidants, N-acetylcysteine (NAC; 33 mM) and AEOL10113 (10-100
      microM), the N-terminal c-jun kinase inhibitor, SP600125 (33 microM), and nuclear
      factor-kappaB inhibitor, SN50 (33 microM), inhibited DEP-induced cell number
      increase. NAC inhibited DEP-induced reduction of G0/1 and increase in cells in
      the S and G2/M phases. Expression of p21CIP1/WAF1 mRNA and protein seen with
      serum starvation was reduced by DEP. In conclusion, diesel exhaust particles
      prevented serum starvation-led decreases in A549 epithelial cells by inducing
      cell cycle progression and preventing apoptosis, processes involving oxidative
      stress, inhibition of p21CIP1/WAF1 expression and stimulation of N-terminal c-jun
      kinase and nuclear factor-kappaB. Therefore, low-dose diesel exhaust particle
      exposure may lead to lung epithelial cell hyperplasia.

PMID- 16455840
TI  - Reducing crude protein in beef cattle diet reduces ammonia emissions from
      artificial feedyard surfaces.
AB  - Concentrated animal feeding operations are major sources of ammonia to the
      atmosphere. Control methods to reduce emissions include acidifying amendments,
      urease inhibitors, and absorbents. For beef cattle, decreasing crude protein (CP)
      in diets may be the most practical and cost-effective method to reduce ammonia
      emissions. Our objective was to quantify the effect of reducing CP in beef cattle
      diet on ammonia emissions. Two groups of steers were fed diets with either 11.5
      or 13.0% CP and all urine and feces were collected. Manures from the two diet
      treatments were applied in a replicated laboratory chamber experiment, and
      ammonia emission was quantified using acid gas washing. In four seasonal field
      trials, manures from the two diet treatments were applied to two 10-m-diameter,
      circular, artificial feedyard surfaces, and ammonia emission was quantified using
      the integrated horizontal flux method. Manure from steers fed 11.5% CP diet had
      less urine, less urinary N, and a lesser fraction of total N in urine, compared
      with the 13.0% CP diet. Decreasing crude protein in beef cattle diets from 13 to
      11.5% significantly decreased ammonia emission by 44% (p < 0.01) in the closed
      chamber laboratory experiment, and decreased mean daily ammonia flux by 30% (p =
      0.10), 52% (p = 0.08), and 29% (p < 0.01) in summer, autumn, and spring field
      trials, respectively. No difference was observed in winter. On an annual basis,
      decreasing crude protein reduced daily ammonia flux by 28%. Reducing crude
      protein in beef cattle diets may provide the most practical and cost-effective
      way to reduce ammonia emissions from feedyards.

PMID- 16455841
TI  - Upflow reactors for riparian zone denitrification.
AB  - We used permeable reactive subsurface barriers consisting of a C source (wood
      particles), with very high hydraulic conductivities ( approximately 0.1-1 cm s(
      1)), to provide high rates of riparian zone NO3-N removal at two field sites in
      an agricultural area of southwestern Ontario. At one site, a 0.73-m3 reactor
      containing fine wood particles was monitored for a 20-mo period and achieved a
      33% reduction in mean influent NO3-N concentration of 11.5 mg L(-1) and a mean
      removal rate of 4.5 mg L(-1) d(-1) (0.7 g m(-2) d(-1)). At the second site, four
      smaller reactors (0.21 m3 each), two containing fine wood particles and two
      containing coarse wood particles, were monitored for a 4-mo period and were
      successful in attenuating mean influent NO3-N concentrations of 23.7 to 35.1 mg
      L(-1) by 41 to 63%. Mean reaction rates for the two coarse-particle reactors (3.2
      and 7.8 mg L(-1) d(-1), or 1.5 and 3.4 g m(-2) d(-1)) were not significantly
      different (p > 0.2) than the rates observed in the two fine-particle reactors
      (5.0 and 9.9 mg L(-1) d(-1), or 1.8-3.5 g m(-2) d(-1)). A two-dimensional ground
      water flow model is used to illustrate how permeable reactive barriers such as
      these can be used to redirect ground water flow within riparian zones,
      potentially augmenting NO3- removal in this environment.

PMID- 16455842
TI  - Spatial analysis of land use impact on ground water nitrate concentrations.
AB  - In spatial analyses of causes or health effects of environmental pollutants,
      small units of analyses are usually preferred for internal environmental
      homogeneity reasons but can only be done when fine resolution data are available
      for most units. Objectives of this study were to determine which land use
      practices were spatially associated with ground water nitrate concentrations
      across Prince Edward Island (PEI), Canada, and which spatial aggregation is the
      preferred unit of analyses. Nitrate concentrations were determined for 4855
      samples from private wells. Validated field-by-field land use data were
      available. Average nitrate concentration and percentage of area for the 14 major
      land use categories in PEI were determined for each of three spatial
      aggregations: watersheds based on topography and hydrology; freeform polygon
      boundaries based on similar neighboring nitrate concentrations; and 500-m buffer
      zones around each well. Results showed that the percentages of potato, grain, and
      hay coverage were positive predictors of ground water nitrate concentrations.
      Percentage of blueberry was a marginally significant negative predictor in the
      watershed and freeform polygon models, and percentage of residential coverage was
      a positive predictor in the freeform polygon and buffer zone models. Spatial
      autocorrelation was present in the freeform polygon and buffer zone models even
      after land use was taken into account. In conclusion, analyses based on
      watersheds produced the best predictive model with the percentages of land cover
      of potato, hay, and grain being significantly associated with ground water
      nitrate concentrations, and the percentages of blueberry, clear-cut woodland, and
      other agriculture being marginally significant.

PMID- 16455843
TI  - Soil acidity and manganese in declining and nondeclining sugar maple stands in
      Pennsylvania.
AB  - For decades, the hardwood forests of northern Pennsylvania have been subjected to
      chronic atmospheric loading of acidifying agents. On marginal, high-elevation,
      unglaciated sites, sugar maples (Acer saccharum Marsh.) have experienced severe
      decline symptoms and mortality. Accelerated soil acidification, base cation
      leaching, and increased availability of toxic metals have been suggested as
      predisposing factors contributing to this decline. Manganese, an essential
      micronutrient, is also a potentially phytotoxic metal that may be a factor
      associated with poor sugar maple health on soils vulnerable to acidification from
      anthropogenic sources. We measured Mn levels in four compartments of the soil
      tree system (soil, foliage, xylem wood, and sap) on three sugar maple stands in
      northern Pennsylvania. Two stands were classified as declining and one was in
      good health. Negative correlations were found between soil pH and Mn levels in
      the soil, foliage, sap, and xylem wood. Levels of Mn in these pools were
      consistently higher on declining sites, which correspondingly exhibited lower
      levels of Ca and Mg. Species differences between red maple (Acer rubrum L.) and
      sugar maple at the two declining sites suggested different tolerances to
      excessive Mn. Molar ratios of Mg/Mn and Ca/Mn were different among sites and
      showed potential as indicators of soil acidification. Significant correlations
      among soil, sap, foliage, and xylem wood Mn were also noted. These results show
      clear Mn differences among sites and, when viewed with recent Mn toxicity
      experiments and other observational studies, suggest that excessive Mn may play a
      role in the observed decline and mortality of sugar maple.

PMID- 16455844
TI  - Leaching of carbonated air pollution control residues using compliance leaching
      tests.
AB  - The leaching characteristics of air pollution control (APC) residues collected in
      Shanghai, China, were compared by performing three compliance leaching tests.
      These were the standard Chinese method for determining the leaching toxicity of
      solid waste (GB 5086.1-1997), the USEPA's Toxicity Characteristic Leaching
      Procedure (TCLP), and the new European shake test (EN 12457-3). In particular,
      behaviors of raw samples and samples that had been subjected to natural aging
      were compared. Both the leaching tests and natural aging substantially affected
      the leaching results concerning the APC residue samples. Most importantly, EN and
      GB tests classified the raw APC residues as hazardous, but the residues passed
      the TCLP test as nonhazardous. After it had been naturally aged for 720 h,
      however, the aged sample was classified as hazardous by the TCLP and EN tests,
      but as nonhazardous by the GB test. Metals that are thought to have been
      immobilized by carbonation were released at pH 6.3. Model calculations based on
      the geochemical thermodynamic equilibrium model MINTEQA2 revealed that the
      formation of metal carbonates did not correspond to the noted change in the
      leaching behaviors in the three leaching tests. Rather, the partial
      neutralization of alkaline ash by dissolved CO2 changing the final pH of the
      leachate dominated the leaching characteristics. The leaching results showed a
      change in leachate pH.

PMID- 16455846
TI  - Predicting soil erosion for alternative land uses.
AB  - The APEX (Agricultural Policy-Environmental eXtender) model developed in the
      United States was calibrated for northwestern China's conditions. The model was
      then used to investigate soil erosion effects associated with alternative land
      uses at the ZFG (Zi-Fang-Gully) watershed in northwestern China. The results
      indicated that the APEX model could be calibrated reasonably well (+/-15% errors)
      to fit those areas with >50% slope within the watershed. Factors being considered
      during calibration include runoff, RUSLE (Revised Universal Soil Loss Equation)
      slope length and steepness factor, channel capacity flow rate, floodplain
      saturated hydraulic conductivity, and RUSLE C factor coefficient. No changes were
      made in the APEX computer code. Predictions suggest that reforestation is the
      best practice among the eight alternative land uses (the status quo, all grass,
      all grain, all grazing, all forest, half tree and half grass, 70% tree and 30%
      grain, and construction of a reservoir) for control of water runoff and soil
      erosion. Construction of a reservoir is the most effective strategy for
      controlling sediment yield although it does nothing to control upland erosion.
      For every 1 Mg of crop yield, 11 Mg of soil were lost during the 30-yr simulation
      period, suggesting that expanding land use for food production should not be
      encouraged on the ZFG watershed. Grass species are less effective than trees in
      controlling runoff and erosion on steep slopes because trees generally have
      deeper and more stable root systems.

PMID- 16455845
TI  - Risk assessment test for lead bioaccessibility to waterfowl in mine-impacted
      soils.
AB  - Due to variations in soil physicochemical properties, species physiology, and
      contaminant speciation, Pb toxicity is difficult to evaluate without conducting
      in vivo dose-response studies. Such tests, however, are expensive and time
      consuming, making them impractical to use in assessment and management of
      contaminated environments. One possible alternative is to develop a
      physiologically based extraction test (PBET) that can be used to measure relative
      bioaccessibility. We developed and correlated a PBET designed to measure the
      bioaccessibility of Pb to waterfowl (W-PBET) in mine-impacted soils located in
      the Coeur d'Alene River Basin, Idaho. The W-PBET was also used to evaluate the
      impact of P amendments on Pb bioavailability. The W-PBET results were correlated
      to waterfowl-tissue Pb levels from a mallard duck [Anas platyrhynchos (L.)]
      feeding study. The W-PBET Pb concentrations were significantly less in the P
      amended soils than in the unamended soils. Results from this study show that the
      W-PBET can be used to assess relative changes in Pb bioaccessibility to waterfowl
      in these mine-impacted soils, and therefore will be a valuable test to help
      manage and remediate contaminated soils.

PMID- 16455847
TI  - Increased wind erosion from forest wildfire: implications for contaminant-related
      risks.
AB  - Assessments of contaminant-related human and ecological risk require estimation
      of transport rates, but few data exist on wind-driven transport rates in
      nonagricultural systems, particularly in response to ecosystem disturbances such
      as forest wildfire and also relative to water-driven transport. The Cerro Grande
      wildfire in May of 2000 burned across ponderosa pine (Pinus ponderosa Douglas ex
      P.&C. Lawson var. scopulorum Englem.) forest within Los Alamos National
      Laboratory in northern New Mexico, where contaminant transport and associated
      post-fire inhalation risks are of concern. In response, the objectives of this
      study were to measure and compare wind-driven horizontal and vertical dust
      fluxes, metrics of transport related to wind erosion, for 3 yr for sites
      differentially affected by the Cerro Grande wildfire: unburned, moderately burned
      (fire mostly confined to ground vegetation), and severely burned (crown fire).
      Wind-driven dust flux was significantly greater in both types of burned areas
      relative to unburned areas, by more than one order of magnitude initially and by
      two to three times 1 yr after the fire. Unexpectedly, the elevated dust fluxes
      did not decrease during the second and third years in burned areas, apparently
      because ongoing drought delayed post-fire recovery. Our estimates enable
      assessment of amplification in contaminant-related risks following a major type
      of disturbance-wildfire, which is expected to increase in intensity and frequency
      due to climate change. More generally, our results highlight the importance of
      considering wind- as well as water-driven transport and erosion, particularly
      following disturbance, for ecosystem biogeochemistry in general and human and
      ecological risk assessment in particular.

PMID- 16455848
TI  - Wildfire effects on soil nutrients and leaching in a tahoe basin watershed.
AB  - A wildfire burned through a previously sampled research site, allowing pre- and
      post-burn measurements of the forest floor, soils, and soil leaching near Lake
      Tahoe, Nevada. Fire and post-fire erosion caused large and statistically
      significant (P < or = 0.05) losses of C, N, P, S, Ca, and Mg from the forest
      floor. There were no statistically significant effects on mineral soils aside
      from a decrease in total N in the surface (A11) horizon, an increase in pH in the
      A11 horizon, and increases in water-extractable SO4(2-) in the A11 and A12
      horizons. Burning caused consistent but nonsignificant increases in exchangeable
      Ca2+ in most horizons, but no consistent or statistically significant effects on
      exchangeable K+ or Mg2+, or on Bray-, bicarbonate-, or water-extractable P
      concentrations. Before the burn, there were no significant differences in
      leaching, but during the first winter after the fire, soil solution
      concentrations of NH4+, NO3-, ortho-P, and (especially) SO4(2-) were elevated in
      the burned area, and resin lysimeters showed significant increases in the
      leaching of NH4+ and mineral N. The leaching losses of mineral N were much
      smaller than the losses from the forest floor and A11 horizons, however. We
      conclude that the major short-term effects of wildfire were on leaching whereas
      the major long-term effect was the loss of N from the forest floor and soil
      during the fire.

PMID- 16455849
TI  - Does calcite encrustation in Chara provide a phosphorus nutrient sink?
AB  - We studied the effect of calcite encrustation in stoneworts (Chara spp.) on P
      cycling in an aquatic ecosystem. Sequential fractionation was performed to
      quantify P fractions of the internodes of calcified (Ca-CF) and uncalcified (UCa
      CF) Chara fibrosa Agardh ex Bruzelius. Our results showed that Ca-CF was able to
      store more P and about 14 to 23% of total P in Ca-CF was co-precipitated with
      encrusted calcite, while only 2 to 3% was found in UCa-CF. Furthermore, in Ca-CF,
      an increased amount of total P did not result in a higher release of bioavailable
      water-soluble and sodium hydroxide-extractable P. Extracellular calcification in
      Chara enhanced nutrient sink for P, provided a further bottom-up control of
      phytoplankton, and should be regarded as a positive feedback in stabilizing Chara
      dominance in lakes.

PMID- 16455850
TI  - Isotopic evidence of nitrate sources and denitrification in the Mississippi
      River, Illinois.
AB  - Anthropogenic nitrate (NO3-) within the Mississippi-Atchafalaya River basin and
      discharge to the Gulf of Mexico has been linked to serious environmental
      problems. The sources of this NO3- have been estimated by others using mass
      balance methods; however, there is considerable uncertainty in these estimates.
      Part of the uncertainty is the degree of denitrification that the NO3- has
      undergone. The isotopic composition of NO3- in the Mississippi River adjacent to
      Illinois and tile drain (subsurface drain) discharge in agricultural areas of
      east-central Illinois was examined using N and O isotopes to help identify the
      major sources of NO3- and assess the degree of denitrification in the samples.
      The isotopic evidence suggests that most of the NO3- in the river is primarily
      derived from synthetic fertilizers and soil organic N, which is consistent with
      published estimates of N inputs to the Mississippi River. The 1:2 relationship
      between delta18O and delta15N also indicate that, depending on sample location
      and season, NO3- in the river and tile drains has undergone significant
      denitrification, ranging from about 0 to 55%. The majority of the denitrification
      appears to have occurred before discharge into the Mississippi River.

PMID- 16455851
TI  - Bedding and within-pen location effects on feedlot pen runoff quality using a
      rainfall simulator.
AB  - Soluble salts, nutrients, and pathogenic bacteria in feedlot-pen runoff have the
      potential to cause pollution of the environment. A 2-yr study (1998-1999) was
      conducted at a beef cattle (Bos taurus) feedlot in southern Alberta, Canada, to
      determine the effect of bedding material [barley (Hordeum vulgare L.) straw
      versus wood chips] and within-pen location on the chemical and bacterial
      properties of pen-floor runoff. Runoff was generated with a portable rainfall
      simulator and analyzed for chemical content (nitrogen [N], phosphorus [P],
      soluble salts, electrical conductivity [EC], sodium adsorption ratio [SAR],
      dissolved oxygen [DO], and pH) and populations of three groups of bacteria
      (Escherichia coli, total coliforms, total aerobic heterotrophs at 27 degrees C)
      in 1998 and 1999. Bedding had a significant (P < or = 0.05) effect on NH4-N
      concentration and load in 1999, SO4 load in 1998, SO4 concentration and load in
      1999, and total coliforms in both years; where these three variables were higher
      in wood than straw pens. Location had a significant effect on EC and
      concentrations of total Kjeldahl nitrogen (TKN), Na, K, SO4, and Cl in 1998, and
      total coliforms in both years. These seven variables were higher at the bedding
      pack than pen floor location, indicating that bedding packs were major reservoirs
      of TKN, soluble salts, and total coliforms. Significantly higher dissolved
      reactive phosphorus (DRP), total P, and NH4-N concentrations and loads at the
      bedding pack location in wood pens in 1998, and a similar trend for TKN
      concentration in 1999, indicated that this bedding-location treatment was a
      greater source of nutrients to runoff than the other three bedding-location
      treatments. Bedding, location, and their interaction may therefore be a potential
      tool to manage nutrients, soluble salts, and bacteria in feedlot runoff.

PMID- 16455853
TI  - Isolation of salmonella bacteriophages from swine effluent lagoons.
AB  - Bacteriophages (phages) associated with Salmonella were collected from nine swine
      manure lagoons in Mississippi. Phages were isolated by an enrichment protocol or
      directly from effluent. For enrichment, chloroform-treated samples were filtered
      (0.22 mum) and selectively enriched by adding a cocktail of Salmonella strains in
      trypticase soy broth. After overnight incubation at 35 degrees C, chloroform was
      added and samples stored at 5 degrees C. Enriched samples were tested by double
      agar layer (DAL) plaque assay against individual Salmonella isolates. Phage
      titers of 2.9 x 10(8) to 2.1 x 10(9) plaque forming units (pfu) per mL were
      produced, but estimation of phage titers in lagoons was not possible. For direct
      isolation, effluent was clarified by centrifugation, filtered (0.22 microm), and
      used in DAL plaque assays to select single-plaque isolates for 15 Salmonella
      strains. Plaque counts varied among Salmonella strains and lagoons. The most
      sensitive strain for direct phage recovery was ATCC 13311. Phage titers estimated
      by direct isolation with ATCC 13311 ranged among lagoons from 12 to 148 pfu per
      mL. In limited host range tests, 66 isolates recovered by the enrichment protocol
      produced plaques only on Enteritidis and Typhimurium strains of Salmonella and
      none produced plaques on lagoon isolates of Citrobacter, Escherichia, Proteus,
      Providencia, or Serratia. Electron microscopy (EM) showed purified enrichment
      isolates had Podoviridae morphology (tailless 50-nm icosahedral heads with tail
      spikes). Electron microscopy of clarified concentrated effluent showed 5.5:1
      tailless to tailed phages. The isolated phages have potential as typing reagents,
      specific indicators, and biocontrol agents of Salmonella.

PMID- 16455852
TI  - A method for measuring low-weight carboxylic acids from biosolid compost.
AB  - Concentration of low-weight carboxylic acids (LWCA) is one of the important
      parameters that should be taken into consideration when compost is applied as
      soil improver for plant cultivation, because high amounts of LWCA can be toxic to
      plants. The present work describes a method for analysis of LWCA in compost as a
      useful tool for monitoring compost quality and safety. The method was tested on
      compost samples of two different ages: 3 (immature) and 6 (mature) months old.
      Acids from compost samples were extracted at high pH, filtered, and freeze-dried.
      The dried sodium salts were derivatized with a sulfuric acid-methanol mixture and
      concentrations of 11 low-weight fatty acids (C1-C10) were analyzed using
      headspace gas chromatography. The material was analyzed with two analytical
      techniques: the external calibration method (tested on 11 LWCA) and the standard
      addition method (tested only on formic, acetic, propionic, butyric, and iso
      butyric acids). The two techniques were compared for efficiency of acids
      quantification. The method allowed good separation and quantification of a wide
      range of individual acids with high sensitivity at low concentrations. Detection
      limit for propionic, butyric, caproic, caprylic, and capric acids was 1 mg kg(-1)
      compost; for formic, acetic, valeric, enanthoic and pelargonic acids it was 5 mg
      kg(-1) compost; and for iso-butyric acid it was 10 mg kg(-1) compost. Recovery
      rates of LWCA were higher in 3-mo-old compost (57-99%) than in 6-mo-old compost
      (29-45%). In comparison with the external calibration technique the standard
      addition technique proved to be three to four times more precise for older
      compost and two times for younger compost. Disadvantages of the standard addition
      technique are that it is more time demanding and laborious.

PMID- 16455854
TI  - Phosphorus release from a manure-impacted spodosol: effects of a water treatment
      residual.
AB  - Long-term depositions of animal manures affect P dynamics in soils and can pose
      environmental risks associated with P losses. Laboratory studies were done on P
      solubility characteristics in a manure-impacted Immokalee soil (sandy, siliceous,
      hyperthermic Arenic Alaquod) and the effectiveness of water treatment residual
      (WTR) in controlling P leaching. Soil samples with contrasting initial total P
      concentrations were prepared by mixing samples of a manure-impacted surface A
      horizon and a minimally P-impacted E horizon. Effects of mixing various ratios of
      A and E horizons, WTR rates (0, 25, 50, and 100 g kg(-1)), and depths of WTR
      incorporation (mixed throughout the soil column or partially incorporated) on P
      leaching were determined. Between 62 and 77% of total P was released from the
      soil mixes by successive water extractions, suggesting a considerable buffering
      capacity of this manure-impacted soil to resupply P into solution. Between 224
      and 408 mg kg(-1) P were leached during the 36-wk leaching period in the absence
      of WTR. Mixing WTRs with soil reduced soluble P concentration in leachates by as
      much as 99.8% compared with samples without WTR. Thoroughly mixing WTR with the
      entire soil column (15 cm) was much more efficient than mixing WTR with only the
      top 7.5 cm of soil. Calcium- and Mg-P forms appear to control P release in soils
      without WTR, whereas sorption-desorption reactions probably determine P leaching
      in WTR-treated samples. Soil P distribution in various chemical forms was
      affected by WTR additions. Data suggest that WTR-immobilized P is stable in the
      long term.

PMID- 16455855
TI  - Distribution of phosphorus in manure slurry and its infiltration after
      application to soils.
AB  - Computer models help identify agricultural areas where P transport potential is
      high, but commonly used models do not simulate surface application of manures and
      P transport from manures to runoff. As part of an effort to model such P
      transport, we conducted manure slurry separation and soil infiltration
      experiments to determine how much slurry P infiltrates into soil after
      application but before rain, thus becoming less available to runoff. We applied
      dairy and swine slurry to soil columns and after both 24 and 96 h analyzed solids
      remaining on the soil surface for dry matter, total phosphorus (TP), and water
      extractable inorganic (WEIP) and organic (WEOP) phosphorus. We analyzed
      underlying soils for Mehlich-3 and water-extractable P. We also conducted slurry
      separation experiments by sieving, centrifuging, and suction-filtering to
      determine which method could easily estimate slurry P infiltration into soils.
      About 20% of slurry solids and 40 to 65% of slurry TP and WEIP infiltrated into
      soil after application, rendering this P less available to transport in runoff.
      Slurry separation by suction-filtering through a screen with 0.75-mm-diameter
      openings was the best method to estimate this slurry P infiltration. Measured
      quantities of manure WEOP changed too much during experiments to estimate WEOP
      infiltration into soil or what separation method can approximate infiltration.
      Applying slurries to soils always increased soil P in the top 0 to 1 cm of soil,
      frequently in the 1- to 2-cm depth of soil, but rarely below 2 cm. Future
      research should use soils with coarser texture or large macropores, and slurry
      with low dry matter content (1-2%).

PMID- 16455856
TI  - Avoidant attachment and the experience of parenting.
AB  - Guided by attachment theory, this research investigated connections between
      avoidant attachment styles and the experience of parenting after the birth of a
      couple's first child. One hundred and six couples completed a battery of measures
      approximately 6 weeks before and 6 months after the birth of their first child.
      As anticipated, parents with more avoidant attachment styles experienced greater
      stress after the birth of their child and perceived parenting as less satisfying
      and personally meaningful. Attachment theory maintains that adult attachment
      styles should affect relationships with adults and with one's children. The
      present findings provide some of the first evidence that self-reported adult
      romantic attachment styles, which have been the focus of attachment research by
      social and personality psychologists, are systematically associated with parent
      child relationships. They also provide insight into the processes through which
      secure and insecure attachment styles might be transmitted from one generation to
      the next.

PMID- 16455857
TI  - Social norms and the likelihood of raping: Perceived rape myth acceptance of
      others affects men's rape proclivity.
AB  - Research showing that rape myth acceptance (RMA) causally affects rape proclivity
      (RP) was extended by examining the impact of RMA-related norms on RP. Male
      students (total N = 264) received feedback about the alleged responses of other
      students to RMA items either before (Experiment 1) or after (Experiment 2) they
      reported their own RMA, and then their RP was assessed using acquaintance-rape
      scenarios. The level of RMA feedback was varied. Results showed that higher norms
      led to higher RP. In Experiment 1, this effect was mediated via self-reported
      RMA. Experiment 2 yielded main effects of both RMA feedback and self-reported RMA
      and an interaction effect showing that RMA feedback was particularly influential
      at higher levels of own RMA. Theoretical and practical implications of these
      findings are discussed.

PMID- 16455858
TI  - Predicting the onset of emotional recovery following nonmarital relationship
      dissolution: survival analyses of sadness and anger.
AB  - Event onset modeling was used to investigate the time course of breakup-related
      affective processes. Daily emotion data were collected for 4 weeks from 58 young
      adults who recently experienced the dissolution of a serious romantic
      relationship. Using baseline data obtained from individuals in intact dating
      relationships, sadness and anger recovery were defined as points in time and then
      modeled as a function of theoretically relevant predictors using Cox's survival
      analysis. Acceptance of relationship termination mediated the association between
      attachment security and sadness recovery. Greater levels of love, anger, and
      attachment preoccupation were associated with a decreased probability of sadness
      recovery during the study period. Attachment security was associated with an
      increased probability of anger recovery, whereas ongoing sadness decreased the
      probability of this event. Discussion centers on the differential functioning of
      sadness and anger as well as the need to consider emotional change as a
      multicomponent process.

PMID- 16455859
TI  - On the benefits of giving as well as receiving autonomy support: mutuality in
      close friendships.
AB  - Two studies examined autonomy support within close friendships. The first showed
      that receiving autonomy support from a friend predicted the recipient's need
      satisfaction within the relationship and relationship quality as indexed by
      emotional reliance, security of attachment, dyadic adjustment, and inclusion of
      friend in self and that there was significant mutuality of receiving autonomy
      support and of each other variable. The relations of perceived autonomy support
      to need satisfaction and relationship quality held for both female-female and
      male-male pairs across the two studies. The second study replicated and extended
      the first, showing that receiving autonomy support also predicted psychological
      health. Furthermore, giving autonomy support to a friend predicted the givers'
      experience of relationship quality over and above the effects of receiving
      autonomy support from the friend. When both receiving and giving autonomy support
      competed for variance in predicting well-being, giving, rather than receiving,
      autonomy support was the stronger predictor.

PMID- 16455860
TI  - The role of self-criticism, dependency, and hassles in the course of depressive
      illness: a multiwave longitudinal study.
AB  - The current study utilized a multiwave longitudinal design to examine whether
      dependency and/or self-criticism influence the course of depressive symptoms in a
      community sample of adults with a history of major depression. In addition, the
      authors examined whether self-esteem serves as a buffer against the development
      of depressive symptoms following increases in hassles in individuals possessing
      such traits. At Time 1, 102 participants completed measures assessing depressive
      symptoms, self-criticism, dependency, and self-esteem. Every 6 weeks for the next
      year, participants completed measures assessing depressive symptoms and hassles.
      High self-criticism was associated with greater elevations in depressive symptoms
      following elevations in hassles in low but not high-self-esteem individuals.
      Results with respect to dependency, however, were contrary to hypotheses. High
      dependency was associated with elevations in depressive symptoms following
      elevations in hassles in high-self-esteem individuals. In contrast, high
      dependency was associated with chronically elevated depressive symptoms in low
      self-esteem individuals.

PMID- 16455861
TI  - The challenge of merging: merger patterns, premerger status, and merger support.
AB  - Employees of merging organizations often show resistance to the merger. The
      employees' support depends on the companies' premerger status and on the merger
      pattern. Based on an intergroup perspective, three studies were conducted to
      investigate the influence of premerger status (high, low) and merger pattern
      (assimilation, integration-equality, integration-proportionality, transformation)
      on participants' support for a pending organizational merger. Students (Study 1)
      and employees (Study 2) had to take the perspective of employees of a fictitious
      merging organization. Study 3 investigated students' perceptions of a potentially
      pending university merger using a 2 (status) x 3 (merger pattern: assimilation,
      integration-equality, integration-proportionality) design. Across all studies,
      the low-status group favored integration-equality and transformation whereas the
      high-status group preferred integration-proportionality and assimilation.
      Perceived threat mediated the effects. Legitimacy was a stronger mediator for
      effects of the low-status group.

PMID- 16455862
TI  - Women's advantage at remembering others' appearance: A systematic look at the why
      and when of a gender difference.
AB  - Women recall the appearance of others better than men. The goal of the present
      research was to shed light on the explanations and boundary conditions of this
      gender difference. In three studies (592 participants), the authors tested
      potential mediators and moderators of the gender difference. Results corroborated
      the robustness of the gender difference. General task motivation, general memory
      ability, importance of appearance, appearance knowledge, attention paid to
      target, gazing at target, and communal or agentic orientation could not explain
      why women were better at recalling others' appearance than men were. Except for
      importance of appearance and appearance knowledge, which both decreased the
      magnitude of the gender difference, general task motivation, attention paid to
      target, length of exposure to target, delay in responding, cognitive load, and
      response format (verbal vs. nonverbal) had no effect on the gender difference.
      Results are discussed in relation to gender differences found in the nonverbal
      sensitivity literature.

PMID- 16455863
TI  - Coping with terrorism: the impact of increased salience of terrorism on mood and
      self-efficacy of intrinsically religious and nonreligious people.
AB  - It was hypothesized that intrinsic religiousness helps to cope with increased
      salience of terrorism. Intrinsically religious and non-religious participants
      were told that it is highly probable or highly improbable, respectively, that
      terrorist attacks will occur in Germany. High probability of terrorism only
      negatively affected the mood of non-religious participants but not of
      intrinsically religious participants (Study 1). Using as a realistic context of
      investigation the terrorist suicide bombings in Istanbul, the authors replicated
      this finding and shed some light on the underlying psychological processes (Study
      2): On the day of the terrorist attacks (high salience of terrorism), non
      religious participants experienced less positive emotions and less self-efficacy
      than did intrinsically religious participants. Two months later (low salience of
      terrorism), no differences were found between non-religious and intrinsically
      religious participants with regard to mood and self-efficacy. Mediational
      analyses suggested that the mood effects were associated with differences in the
      reported sense of self-efficacy.

PMID- 16455864
TI  - Approach and avoidance motivation in the social domain.
AB  - This research put Gable's (in press) hierarchical model of approach-avoidance
      social motivation to empirical test using newly developed measures of friendship
      approach and avoidance goals. The results from Study 1 supported the psychometric
      soundness of the new goal measures and showed the anticipated differential
      predictive patterns for the two goals. The results from Study 2 provided further
      evidence of the psychometric soundness of the new goal measures and provided
      support for the full hierarchical model in longitudinal analyses of subjective
      well-being and physical symptomotology. Implications of the present research for
      understanding motivation both within and beyond the social domain are discussed.

PMID- 16455865
TI  - From fault line to group fission: understanding membership changes in small
      groups.
AB  - Group fissions occur when two or more members leave a parent group to either form
      a new group or join an existing group. This article investigates the interplay
      between two factors: the presence of an intragroup conflict and subgroup
      boundaries on the group fission process. It is hypothesized that subgroup
      divisions act as potential fault lines along which groups split after they
      experience conflict. The results of three experiments, one scenario study and two
      laboratory studies involving small task groups, support the group fault line
      hypothesis. The authors discuss the implications of these findings for theory and
      research on membership changes in small groups.

PMID- 16455866
TI  - Effects of mortality salience on evaluation of ingroup and outgroup sources: the
      impact of pro- versus counterattitudinal positions.
AB  - Past Terror Management Theory (TMT) research has demonstrated that mortality
      salience leads to favoritism toward ingroup members and derogation of outgroup
      members and to polarized attitudes toward the source of pro and
      counterattitudinal statements. In such research, the individual's group
      membership and the individual's worldview position were examined separately.
      Thus, when the individual's group membership was manipulated, one could normally
      assume that an outgroup member is counterattitudinal and an ingroup member is
      proattitudinal. It is unclear, therefore, whether ingroup members elicited
      favoritism from mortality salient participants because of their group membership
      or because of their presumably proattitudinal position, or both. The authors
      present two studies in which the individual's group membership and attitudinal
      position are jointly manipulated. Results showed that among mortality salient
      participants, the outgroup member received favorable or unfavorable evaluations
      depending on his position, whereas the ingroup member received moderately
      positive evaluations regardless of the position taken.

PMID- 16455867
TI  - Benchmark for evaluating the quality of DNA sequencing: proposal from an
      international external quality assessment scheme.
AB  - BACKGROUND: In the past 15 years, clinical laboratory science has been
      transformed by the use of technologies that cross the traditional boundaries
      between laboratory disciplines. However, during this period, issues of quality
      have not always been given adequate attention. The European Molecular Genetics
      Quality Network (EMQN) has developed a novel external quality assessment scheme
      for evaluation of DNA sequencing. We report the results of an international
      survey of the quality of DNA sequencing among 64 laboratories from 21 countries.
      METHODS: Current practice for DNA sequence analysis was established by use of an
      online questionnaire. Participating laboratories were provided with 4 DNA samples
      of validated genotype. Evaluation of the results included assessing the quality
      of sequence data, variant genotypes, and mutation nomenclature. To accommodate
      variations in mutation nomenclature, variants indicated by participants were
      scored for compliance with 3 acceptable marking schemes. RESULTS: A total of 346
      genotypes were analyzed. Of these, 19 (5%) genotyping errors were made. Of these,
      10 (53%) were false-negative and 9 (47%) were false-positive results. A further
      27 (8%) errors were made in naming mutations. Results were analyzed for 3
      indicators of data quality: PHRED quality scores, Quality Read Length, and
      Quality Read Overlap. Most laboratories produced results of acceptable diagnostic
      quality as judged by these indicators. The results were used to calculate a
      consensus benchmark for DNA sequencing against which individual laboratories
      could rank their performance. CONCLUSIONS: We propose that the consensus
      benchmark can be used as a baseline against which the aggregate and individual
      laboratory standard of DNA sequencing may be tracked from year to year.

PMID- 16455868
TI  - Pretreatment plasma folate modulates the pharmacodynamic effect of high-dose
      methotrexate in children with acute lymphoblastic leukemia and non-Hodgkin
      lymphoma: "folate overrescue" concept revisited.
AB  - BACKGROUND: To evaluate the influence of pretreatment plasma folate
      concentrations on methotrexate exposure in children with acute lymphoblastic
      leukemia/non-Hodgkin lymphoma treated with high-dose methotrexate, we assessed
      time profiles of plasma homocysteine, folate, and vitamin B(12) concentrations in
      children treated with high-dose methotrexate with leucovorin rescue. METHODS: We
      analyzed 98 treatment courses. The study endpoints were to determine how
      methotrexate exposure is related to homocysteine accumulation and whether it is
      influenced by pretreatment plasma folate. RESULTS: Peak concentrations of
      homocysteine increased from the start of the intravenous infusion through
      cessation of methotrexate therapy up to time point t(42), when this trend was
      reversed by administration of folinic acid. The area under the curve (AUC) for
      plasma homocysteine showed decreasing course-to-course tendencies with a
      statistically significant decrease only between courses 1 and 2 (P <or=0.05),
      indicating decreased whole-body homocysteine accumulation in response to
      administration of consecutive methotrexate courses. Therapeutic courses with low
      initial folate concentrations (<or=10 nmol/L) gave significantly higher responses
      in homocysteine accumulation expressed both as (hcys)AUC(0-66 h) and the peak
      t(42) homocysteine concentrations than did courses with initial folate >10
      nmol/L. Correspondingly, in the courses with low initial folate, peak plasma
      concentrations of methotrexate were significantly higher than in courses with
      high precourse concentrations of plasma folate. CONCLUSION: Endogenous
      pretreatment plasma folate modulates the magnitude of the methotrexate effect,
      providing support for a "folate overrescue" concept.

PMID- 16455869
TI  - Differentiation of amphetamine/methamphetamine and other cross-immunoreactive
      sympathomimetic amines in urine samples by serial dilution testing.
AB  - BACKGROUND: Immunoassay-based screening for amphetamines has a variable positive
      predictive value (PPV) for detecting amphetamine abuse. The lack of immunoassay
      specificity necessitates confirmatory testing by gas chromatography-mass
      spectrometry (GC/MS), but the technical complexity and expense of GC/MS limit its
      availability. Physicians may make decisions regarding patient disposition based
      on unverified results. In this study we assessed the utility of using dose
      response properties to distinguish urine samples containing amphetamines from
      samples containing cross-immunoreactive species. METHODS: Urine was supplemented
      with known concentrations of amphetamine, methamphetamine,
      methylenedioxymethamphetamine (MDMA), or pseudoephedrine. Using a series of
      dilutions, we determined the maximum change in rate over the fractional change in
      concentration for each compound in the Emit II amphetamine/methamphetamine
      immunoassay. Patient urine samples that screened positive for amphetamines were
      diluted 1:1, 1:10, and 1:20, and maximum slope estimates within the dynamic assay
      range were determined. An optimal slope cutoff that differentiated samples
      containing (meth)amphetamine from those containing cross-reacting species was
      determined by ROC analysis. RESULTS: The slope of the dose response was largest
      for amphetamine and methamphetamine, followed by MDMA and pseudoephedrine. The
      optimum slope cutoff for identifying patient specimens containing
      (meth)amphetamine was 320 (sensitivity, 96%; specificity, 90%; PPV, 92%). High
      concentrations of less reactive compounds may mask low concentrations of
      amphetamines. CONCLUSIONS: Use of the slope of the dose-response relationship in
      patient urine specimens can enhance the PPV of presumptive positive immunoassay
      results but does not exclude the presence of low amphetamine concentrations in
      samples containing high concentrations of cross-reactive species.

PMID- 16455870
TI  - Multiplex tetra-primer amplification refractory mutation system PCR to detect 6
      common germline mutations of the MUTYH gene associated with polyposis and
      colorectal cancer.
AB  - BACKGROUND: We describe a simple tetra-primer amplification refractory mutation
      system PCR (T-ARMS-PCR) for detecting MUTYH mutations, which are associated with
      colorectal adenomas and colorectal cancer. METHODS: We designed specific T-ARMS
      PCR assays for 6 mutations (Y165C, G382D, 1395_7delGGA, Y90X, 1103delC, and
      R231H) selected on the basis of the frequency of their occurrence. We also
      designed a set of 3 multiplex T-ARMS PCR assays, each for detection of 2
      mutations. We tested DNA samples from patients with attenuated or classic
      adenomatous polyposis coli and no detectable APC germline mutations. RESULTS: All
      mutations were easily detected with both the specific and multiplex T-ARMS-PCR
      assays. Results were confirmed by DNA HPLC analysis in all 54 patients, and each
      mutation was confirmed by direct DNA sequencing. CONCLUSIONS: T-ARMS-PCR does not
      require any special equipment, and it provides rapid, reproducible, and cost
      effective detection of common MUTYH mutations. Multiplex T-ARMS-PCR allows the
      detection of 6 common MUTYH mutations with use of as few as 3 single tube PCR
      reactions. It could be useful to carry out large population-based epidemiologic
      studies.

PMID- 16455871
TI  - Osmolality gaps: diagnostic accuracy and long-term variability.
AB  - BACKGROUND: The osmolal gap (OG) is a screening test for the detection of toxic
      volatiles such as methanol and ethylene glycol. We used mean values of patient
      data to assess the diagnostic accuracy and long-term stability of OG
      measurements. METHODS: In a prospective study period in 2003, all requests for
      volatiles had OGs calculated and quality-control samples were analyzed for OG.
      ROC curves were constructed to determine whether OG could predict the presence of
      toxic volatiles in serum. This was also done in a retrospective study for data
      from 1996 to 2004. Our laboratory database was searched for all emergency room
      patients for the period of 1996 to 2004 who had tests ordered that allowed us to
      calculate OGs. RESULTS: For the prospective study period in 2003, the ROC areas
      indicated that we could accurately predict the presence of toxic volatiles but at
      markedly different decision cutpoints depending on the formula used. These
      cutpoints ranged from +10 to +33 mosmol/kg. In the retrospective study, the mean
      OGs in the patient population for each of the 3 formulas increased by 12
      mosmol/kg from 1996 to 2004. For this reason, the diagnostic accuracy was poor
      when all data were analyzed together. CONCLUSIONS: Under properly controlled
      conditions, the OG has high sensitivity and specificity for detection of
      poisoning with some volatiles. Over the long term, however, use of the reference
      interval of -10 to +10 mosmol/kg yields poor diagnostic accuracy because mean OGs
      are not constant over time. Bedside calculation is not advisable.

PMID- 16455872
TI  - Purified excreted-secreted antigens from Trypanosoma cruzi trypomastigotes as
      tools for diagnosis of Chagas' disease.
AB  - There is currently no "gold standard" test for the diagnosis of late-stage
      Chagas' disease. As a result, protection of the blood supply in areas where
      Chagas' disease is endemic remains problematic. A panel of 709 serum samples from
      subjects with confirmed Chagas' disease (n = 195), healthy controls (n = 400),
      and patients with other parasitic diseases (n = 114) was used to assess enzyme
      linked immunosorbent assays (ELISAs) based on a concentrated extract of excretory
      secretory antigens from either Brazil or Tulahuen strain Trypanosoma cruzi
      trypomastigotes (total trypomastigote excretory-secretory antigens [TESAs]). The
      total TESA-based assays had excellent overall sensitivity (100%) and specificity
      (>94%), except for cross-reactivity with Leishmania-infected sera. In an attempt
      to increase the specificity of the assay, immunoaffinity chromatography was used
      to purify the TESA proteins (TESA(IA) proteins). By Western blotting, a series of
      polypeptide bands with molecular masses ranging from 60 to 220 kDa were
      recognized by pooled sera positive for Chagas' disease. An ELISA based on
      TESA(IA) proteins had a slightly lower sensitivity (98.6%) but an improved
      specificity (100%) compared to the sensitivity and specificity of the total TESA
      protein-based ELISAs. A 60-kDa polypeptide was identified as a major contributor
      to the cross-reactivity with Leishmania. These data suggest the need for field
      validation studies of TESA- and TESA(IA)-based assays in regions where Chagas'
      disease is endemic.

PMID- 16455873
TI  - Restricted infectivity of a human-Lineage H3N2 influenza A virus in pigs is
      hemagglutinin and neuraminidase gene dependent.
AB  - Influenza A viruses cause pandemics at sporadic intervals. Pandemic viruses can
      potentially be introduced into the human population through in toto transfer of
      an avian influenza virus or through reassortment between avian and human strains.
      Pigs are believed to play a central role in the creation of pandemic viruses
      through reassortment because of their susceptibility to infection with both avian
      and human influenza viruses. However, we recently found that a human-lineage H3N2
      influenza virus was highly restricted in its ability to infect pigs after
      intranasal inoculation. We hypothesized that this restricted infectivity
      phenotype was controlled by the hemagglutinin (HA) and neuraminidase (NA). To
      test this, we infected pigs with reverse genetics-created HA plus NA reassortant
      viruses. Specifically, introduction of the HA and NA genes of a contemporary H3N2
      swine virus into the genetic background of the wholly human virus resulted in a
      significant increase in virus shedding and pathogenicity. These data indicate
      that the HA/NA can play important roles in controlling human influenza virus
      infectivity in pigs. The results further support the premise that a barrier
      exists to human influenza virus infection in pigs, which may limit the role of
      pigs in pandemic virus creation through reassortment of human and avian influenza
      viruses.

PMID- 16455874
TI  - Rapid detection of Mycobacterium tuberculosis Beijing genotype strains by real
      time PCR.
AB  - Mycobacterium tuberculosis strains of the Beijing genotype were first identified
      in China and neighboring countries and have attracted special attention due to
      their global emergence and association with drug resistance. To further analyze
      the spread and special characteristics of Beijing genotype strains, accurate,
      rapid and sensitive methods that overcome the drawbacks of the classical methods
      such as IS6110 DNA fingerprinting or spoligotyping for the identification of
      strains of this genotype are needed. Based on the nucleotide sequences of M.
      tuberculosis SAWC0780 and H37Rv, primers and fluorogenic 5' nuclease (TaqMan)
      probes for real-time PCR assays specific for Beijing and non-Beijing strains,
      respectively, were designed. The detection limits for the real-time PCR assays
      were about 5 and 10 copies of chromosomal DNA, respectively. In mixtures of
      Beijing and non-Beijing DNA, a multiplex assay was able to detect (i) one copy of
      Beijing DNA in approximately 1,000 copies of non-Beijing DNA and (ii) one copy of
      non-Beijing DNA in approximately 2,000 copies of Beijing DNA. In a blinded
      analysis of a collection of 103 multidrug-resistant strains isolated in Germany
      in 2001, all 62 Beijing and all 41 non-Beijing strains were correctly identified.
      In conclusion, the real-time assay allows for the rapid and specific detection of
      Beijing and non-Beijing strains. The major advantages of this test in comparison
      to other methods used for the identification of Beijing strains are its
      simplicity and sensitivity and the fact that amplification and detection occur
      within one reaction tube.

PMID- 16455875
TI  - Isolation of Corynebacterium tuscaniae sp. nov. from blood cultures of a patient
      with endocarditis.
AB  - A strain of an unknown coryneform bacterium was repeatedly isolated in pure
      culture from the blood of a patient affected by endocarditis. Comparative 16S
      rRNA gene sequence analysis revealed that this isolate represented a new subline
      within the genus Corynebacterium. This new taxon can be identified by the
      presence of corynomycolic acids and its enzymatic activities and fermentation of
      sugars. Acid production from glucose and maltose, pyrazinamidase and alkaline
      phoshatase activities, and hippurate hydrolysis were the most characteristic
      phenotypic features of the bacterium. On the basis of both phenotypic and
      phylogenetic evidence, it is proposed that this isolate be classified as a novel
      species, Corynebacterium tuscaniae sp. nov. The type strain, ISS-5309, has been
      deposited in the American Type Culture Collection (ATCC BAA-1141) and in the
      Culture Collection of the University of Goteborg (CCUG 51321).

PMID- 16455876
TI  - Shiga toxins present in the gut and in the polymorphonuclear leukocytes
      circulating in the blood of children with hemolytic-uremic syndrome.
AB  - Hemolytic-uremic syndrome, the main cause of acute renal failure in early
      childhood, is caused primarily by intestinal infections from some Escherichia
      coli strains that produce Shiga toxins. The toxins released in the gut are
      targeted to renal endothelium after binding to polymorphonuclear leukocytes. The
      presence of Shiga toxins in the feces and the circulating neutrophils of 20
      children with hemolytic uremic syndrome was evaluated by the Vero cell
      cytotoxicity assay and flow cytometric analysis, respectively. The latter showed
      the presence of Shiga toxins on the polymorphonuclear leukocytes of 13 patients,
      5 of whom had no other microbiologic or serologic evidence of infection by Shiga
      toxin-producing Escherichia coli. A positive relationship was observed between
      the amounts of Shiga toxins released in the intestinal lumen and those released
      in the bloodstream. The toxins were detectable on the neutrophils for a median
      period of 5 days after they were no longer detectable in stools. This
      investigation confirms that the immunodetection of Shiga toxins on neutrophils is
      a valuable tool for laboratory diagnosis of Shiga toxin-producing Escherichia
      coli infection in hemolytic-uremic syndrome and provides clues for further
      studies on the role of neutrophils in the pathogenesis of this syndrome.

PMID- 16455877
TI  - Evaluation of the invader assay for genotyping hepatitis C virus.
AB  - The Invader 1.0 assay (Invader HCV Genotyping Assay, version 1.0; Third Wave
      Technologies, Inc., Madison, WI) has been developed for the rapid differentiation
      of hepatitis C virus (HCV) genotypes 1 to 6 based on sequence variation within
      the HCV 5' noncoding (NC) region. In the present study, we evaluated the
      compatibility of Invader 1.0 with the COBAS MONITOR (COBAS AMPLICOR HCV MONITOR
      Test, version 2.0; Roche Molecular Systems, Inc., Branchburg, NJ), COBAS AMPLICOR
      (COBAS AMPLICOR Hepatitis C Virus Test, version 2.0; Roche Molecular Systems,
      Inc.), and COBAS TaqMan (COBAS TaqMan HCV Test; Roche Molecular Systems, Inc.)
      assays. The minimum HCV RNA titers required for successful HCV genotyping (>/=90%
      success rate) were 1,000 IU/ml for COBAS MONITOR, 100 IU/ml for COBAS AMPLICOR,
      and 10 IU/ml for COBAS TaqMan. Invader 1.0 results obtained from unpurified COBAS
      TaqMan amplification products of 111 retrospectively selected clinical serum
      specimens (genotypes 1 to 6, with virus titers ranging from 15.1 to 2.1 x 10(7)
      IU/ml) showed 98% concordance with results obtained from the TRUGENE HCV 5' NC
      Genotyping Kit (Bayer HealthCare LLC, Tarrytown, NY), used in conjunction with
      COBAS AMPLICOR. Although the assay is sensitive, accurate, and easy to perform,
      additional optimization of the Invader 1.0 interpretive software (Invader Data
      Analysis Worksheet) may be necessary to reduce potential misidentification of HCV
      genotypes in low-titer specimens. In summary, Invader 1.0 is compatible with a
      variety of commercially available PCR-based HCV 5' NC region amplification assays
      and is suitable for routine HCV genotyping in clinical laboratories.

PMID- 16455878
TI  - Activities of micafungin against 315 invasive clinical isolates of fluconazole
      resistant Candida spp.
AB  - Micafungin is a new echinocandin exhibiting broad-spectrum activity against
      Candida spp. The activity of the echinocandins against Candida species known to
      express intrinsic or acquired resistance to fluconazole is of interest. We
      determined the MICs of micafungin and caspofungin against 315 invasive clinical
      (bloodstream and other sterile-site) isolates of fluconazole-resistant Candida
      species obtained from geographically diverse medical centers between 2001 and
      2004. MICs were determined using broth microdilution according to the CLSI
      reference method M27-A2. RPMI 1640 was used as the test medium, and we used the
      MIC endpoint of prominent growth reduction at 24 h. Among the 315 fluconazole
      resistant Candida isolates, 146 (46%) were C. krusei, 110 (35%) were C. glabrata,
      41 (13%) were C. albicans, and 18 (6%) were less frequently isolated species.
      Micafungin had good in vitro activity against all fluconazole-resistant Candida
      spp. tested; the MICs at which 50% (MIC(50)) and 90% (MIC(90)) of isolates were
      inhibited were 0.03 microg/ml and 0.06 microg/ml, respectively. All the
      fluconazole-resistant Candida spp. were inhibited at a micafungin MIC that was
      </=1 microg/ml. Among the most common fluconazole-resistant Candida spp. tested
      in the collection, C. glabrata exhibited the lowest micafungin MICs (MIC(90),
      </=0.015 microg/ml), followed by C. albicans (MIC(90), 0.03 microg/ml) and C.
      krusei (MIC(90), 0.06 microg/ml). The new echinocandin micafungin has excellent
      in vitro activity against 315 invasive clinical isolates of fluconazole-resistant
      Candida, which represents the largest collection to date of fluconazole-resistant
      Candida isolates tested against micafungin. Micafungin may prove useful in the
      treatment of infections due to azole-resistant Candida.

PMID- 16455880
TI  - Evaluation of the new GenoType Mycobacterium assay for identification of
      mycobacterial species.
AB  - The new commercial assay GenoType Mycobacterium, intended for the identification
      of mycobacteria, was evaluated with a panel of 197 strains belonging to 86
      different taxa. The system, which relies on solid-phase reverse hybridization, is
      composed of two different kits: GenoType CM for the identification of more
      frequently detected mycobacterial species and GenoType AS for less common
      species. The sensitivity and specificity were 97.9% and 92.4% for the CM kit and
      99.3% and 99.4% for the AS kit. Our results show that the system may represent a
      useful tool to substantially enlarge the number of mycobacteria that can be
      reliably identified in clinical laboratories.

PMID- 16455879
TI  - Emergence of a new norovirus genotype II.4 variant associated with global
      outbreaks of gastroenteritis.
AB  - Norovirus (NoV) is highly infectious and is the major cause of outbreak
      gastroenteritis in adults, with pandemic spread of the virus being reported in
      1995 and 2002. The NoV genome is genetically diverse, which has hampered
      development of sensitive molecular biology-based methods. In this study we report
      on a nested reverse transcriptase PCR (nRT-PCR) that was designed to amplify the
      highly conserved 3' end of the polymerase region and the 5' end of the capsid
      gene of NoV genogroup II (GII). The nRT-PCR was validated with strains isolated
      from sporadic and outbreak cases between 1997 and 2004 in New South Wales,
      Australia. Phylogenetic analysis identified six genotypes circulating in New
      South Wales, GII.1, GII.3, GII.4, GII.6, GII.7, and GII.10, with GII.4 being the
      predominant genotype. In 2004, there was a marked increase in NoV GII activity in
      Australia, with a novel GII.4 variant being identified as the etiological agent
      in 18 outbreaks investigated. This novel GII.4 variant, termed Hunter virus,
      differed by more than 5% at the amino acid level across the capsid from any other
      NoV strain in the GenBank and EMBL databases. The Hunter virus was subsequently
      identified as the etiological agent in large epidemics of gastroenteritis in The
      Netherlands, Japan, and Taiwan in 2004 and 2005.

PMID- 16455881
TI  - Molecular identification of zygomycetes from culture and experimentally infected
      tissues.
AB  - Mucormycosis is an emerging infection associated with a high mortality rate.
      Identification of the causative agents remains difficult and time-consuming by
      standard mycological procedures. In this study, internal transcribed spacer (ITS)
      sequencing was validated as a reliable technique for identification of
      Zygomycetes to the species level. Furthermore, species identification directly
      from infected tissues was evaluated in experimentally infected mice. Fifty-four
      Zygomycetes strains belonging to 16 species, including the most common pathogenic
      species of Rhizopus spp., Absidia spp., Mucor spp., and Rhizomucor spp., were
      used to assess intra- and interspecies variability. Ribosomal DNA including the
      complete ITS1-5.8S-ITS2 region was amplified with fungal universal primers,
      sequenced, and compared. Overall, for a given species, sequence similarities
      between isolates were >98%. In contrast, ITS sequences were very different
      between species, allowing an accurate identification of Zygomycetes to the
      species level in most cases. Six species (Rhizopus oryzae, Rhizopus microsporus,
      Rhizomucor pusillus, Mucor circinelloides, and Mucor indicus) were also used to
      induce disseminated mucormycosis in mice and to demonstrate that DNA extraction,
      amplification of fungal DNA, sequencing, and molecular identification were
      possible directly from frozen tissues.

PMID- 16455882
TI  - Comparison of two commercially available DNA line probe assays for detection of
      multidrug-resistant Mycobacterium tuberculosis.
AB  - Two commercially available DNA line probe assays, Genotype MTBDR and INNO-LiPA
      Rif. TB, were evaluated for their abilities to detect resistance to isoniazid
      (INH) and rifampin (RIF) in 52 Mycobacterium tuberculosis isolates. The test
      results were compared to those obtained by phenotypic drug susceptibility testing
      and sequencing. Compared to the results of phenotypic drug susceptibility
      testing, the Genotype MTBDR test results were concordant for INH for 47 of the 52
      (90.4%) isolates, and both the Genotype MTBDR and the INNO-LiPA Rif. TB test
      results were concordant for RIF for 51 of the 52 (98.1%) isolates. The Genotype
      MTBDR test results correlated with the sequencing results for 48 of the 52
      (92.3%) isolates and the INNO-LiPA Rif. TB results for 50 of the 52 (96.2%)
      isolates. Both assays are useful for the rapid screening of M. tuberculosis
      isolates obtained from patients suspected of having multidrug-resistant
      tuberculosis, but the GenoType MTBDR assay has the advantage of being able to
      detect resistance to both INH and RIF simultaneously.

PMID- 16455883
TI  - Correlation of disease severity with fecal toxin levels in patients with
      Clostridium difficile-associated diarrhea and distribution of PCR ribotypes and
      toxin yields in vitro of corresponding isolates.
AB  - We investigated in vivo and in vitro yields of toxins A and B from and PCR
      ribotypes of Clostridium difficile isolates from 164 patients with differing
      severities of C. difficile-associated diarrhea (CDAD) (patients were grouped as
      follows: <3 loose stools per day, n = 45; 3 to 10 per day, n = 97; >10 per day, n
      = 22). The median fecal toxin levels in each group were 0.5, 6.8, and 149 U/g
      feces (P < 0.001), respectively. Patients with severe diarrhea also had more
      frequent occurrence of blood in stool and vomiting, but there was no association
      with fecal toxin levels per se. There was no correlation between fecal toxin
      level and toxin yield in vitro for the corresponding C. difficile isolate or
      between its PCR ribotype and disease severity. A broad range of toxin yields
      among isolates belonging to major PCR ribotypes indicated a presence of many
      subtypes. We hypothesize that bacterial and host factors that affect C. difficile
      toxin levels in feces are important determinants of symptoms in CDAD patients. An
      inverse correlation between toxin yield and spore count (r = 0.66) in stationary
      phase cultures supported the notion that toxin production and sporulation
      represent opposite alternative survival strategies for C. difficile cells facing
      nutrient shortage.

PMID- 16455884
TI  - Epidemiological and genetic correlates of severe acute respiratory syndrome
      coronavirus infection in the hospital with the highest nosocomial infection rate
      in Taiwan in 2003.
AB  - Taiwan experienced a series of outbreaks of nosocomial severe acute respiratory
      syndrome (SARS) infections in 2003. Two months after the final outbreak, we
      recruited 658 employees from the hospital that suffered the first and most severe
      SARS infections to help us investigate epidemiological and genetic factors
      associated with the SARS coronavirus (SARS-CoV). SARS-CoV infections were
      detected by using enzyme immunoassays and confirmed by a combination of Western
      blot assays, neutralizing antibody tests, and commercial SARS tests. Risk factors
      were analyzed via questionnaire responses and sequence-specific oligonucleotide
      probes of human leukocyte antigen (HLA) alleles. Our results indicate that 3%
      (20/658) of the study participants were seropositive, with one female nurse
      identified as a subclinical case. Identified SARS-CoV infection risk factors
      include working in the same building as the hospital's emergency room and
      infection ward, providing direct care to SARS patients, and carrying a Cw*0801
      HLA allele. The odds ratio for contracting a SARS-CoV infection among persons
      with either a homozygous or a heterozygous Cw*0801 genotype was 4.4 (95%
      confidence interval, 1.5 to 12.9; P = 0.007).

PMID- 16455885
TI  - Use of an adaptation of a commercially available PCR assay aimed at diagnosis of
      chlamydia and gonorrhea to detect Trichomonas vaginalis in urogenital specimens.
AB  - Trichomonas vaginalis PCR using reagents from a commercially available assay for
      Chlamydia trachomatis and Neisseria gonorrhoeae was evaluated for detection of
      infection in women and men attending a sexually transmitted disease clinic.
      Evaluations included three primer sets, endocervical swabs, vaginal swabs and
      urine, and various storage conditions. The TVK3/TVK7 primer set was optimal in
      our hands with sensitivities ranging from 69.5 to 96.8%. In all comparisons, T.
      vaginalis PCR performed better than routine diagnostics using microscopy for
      women and culture for men (P > 0.05). The assay performed well for all sample
      types tested, and vaginal swabs were stable for up to 7 days at ambient
      temperature. Using samples prepared for, and reagents from, the C. trachomatis-N.
      gonorrhoeae PCR assay allowed incorporation of T. vaginalis PCR diagnosis into
      routine clinical testing.

PMID- 16455886
TI  - Locus-specific mutational events in a multilocus variable-number tandem repeat
      analysis of Escherichia coli O157:H7.
AB  - Multilocus variable-number tandem repeat analysis (MLVA) is a validated molecular
      subtyping method for detecting and evaluating Escherichia coli O157:H7 outbreaks.
      In a previous study, five outbreaks with a total of 21 isolates were examined by
      MLVA. Nearly 20% of the epidemiologically linked strains were single-locus
      variants (SLV) of their respective predominant outbreak clone. This result
      prompted an investigation into the mutation rates of the seven MLVA loci (TR1 to
      TR7). With an outbreak strain that was an SLV at the TR1 locus of the predominant
      clone, parallel and serial batch culture experiments were performed. In a
      parallel experiment, none (0/384) of the strains analyzed had mutations at the
      seven MLVA loci. In contrast, in the two 5-day serial experiments, 4.3% (41/960)
      of the strains analyzed had a significant variation in at least one of these loci
      (P < 0.001). The TR2 locus accounted for 85.3% (35/41) of the mutations, with an
      average mutation rate of 3.5 x 10(-3); the mutations rates for TR1 and TR5 were
      10-fold lower. Single additions accounted for 77.1% (27/35) of the mutation
      events in TR2 and all (6/6) of the additions in TR1 and TR5. The remaining four
      loci had no slippage events detected. The mutation rates were locus specific and
      may impact the interpretation of MLVA data for epidemiologic investigations.

PMID- 16455887
TI  - Influence of anti-FloR antibody on florfenicol accumulation in florfenicol
      resistant Escherichia coli and enzyme-linked immunosorbent assay for detection of
      florfenicol-resistant E. coli isolates.
AB  - To detect florfenicol-resistant Escherichia coli isolates by enzyme-linked
      immunosorbent assay (ELISA), anti-FloR1 antibodies were produced in mice using a
      recombinant glutathione S-transferase (GST)-FloR1 protein, which was expressed in
      a prokaryote expression system, as the antigen. The specificity of the murine
      anti-GST-FloR1 antibody and its influence on florfenicol accumulation in
      florfenicol-resistant isolates were investigated using Western blotting and high
      performance liquid chromatography, respectively. Western blotting using the anti
      FloR1 antibody showed specific binding of the antibody to the florfenicol
      resistant FloR protein. Preincubation of florfenicol-resistant strains with the
      antibody significantly increased the intracellular accumulation of florfenicol
      and enhanced the bacterial susceptibility to florfenicol, suggesting that
      antibody binding to the FloR protein inhibited the activity of the efflux protein
      conferred by the floR gene. Analyses of florfenicol-resistant and -sensitive
      isolates by ELISA using the anti-FloR1 antibody showed good correlation between
      FloR protein expression and the floR genotype. The anti-FloR1 antibody-based
      ELISA is a useful tool for the detection of florfenicol-resistant bacteria
      harboring the floR gene.

PMID- 16455888
TI  - Validation of a multiplex pneumococcal serotyping assay with clinical samples.
AB  - We have recently developed a rapid pneumococcal serotyping method called
      "multibead assay" (J. Yu et al., J. Clin. Microbiol. 43:156-162, 2005) based on a
      multiplexed immunoassay for capsular polysaccharides in lysates of pneumococcal
      cultures. The multibead assay can identify 36 serotypes (1, 2, 3, 4, 5, 6A, 6B,
      7A/7F, 8, 9L/9N, 9V, 10A/10B/39/33C, 11A/11D/11F, 12A/12B/12F, 14, 15B/5C, 17F,
      18C, 19A, 19F, 20, 22A/22F, 23F, and 33A/33F). More than 90% of the U.S. isolates
      express one of these serotypes (J. B. Robbins et al., J. Infect. Dis. 148:1136
      1159, 1983). To validate the new assay, we examined 495 clinical isolates of
      pneumococci obtained in Brazil, Denmark, and Mexico. Pneumococci were serotyped
      by the Neufeld test in their countries of origin, and lysates of each strain were
      coded and mailed to the United States for the multibead assay at ambient
      temperature without any thermal protection. After breaking the code, 54
      discrepancies (11% of samples) were noted, but 46 were due to nonreproducible
      technical problems or insufficient growth of the pneumococci. All of the isolates
      grew well for a second test, and therefore, the culture medium used for the
      multibead assay is adequate. The discrepancies persisted for eight isolates,
      involving the 6A, 11A, and 18C serotypes. Additional studies of the eight
      isolates showed that the discrepancies were due to differences in the reagents
      used in the multibead or Neufeld tests for these three serotypes. For instance,
      five isolates were typed as 6A with the Neufeld test but as nontypeable by the
      multibead assay. Selection of another new monoclonal antibody (Hyp6AG1) for the
      multibead assay resulted in all five discrepant isolates typing as 6A. This
      finding indicates the validity of the multibead assay and emphasizes the need to
      validate any new pneumococcal serotyping assay with a large number of clinical
      isolates from different locations. It also suggests the presence of serological
      subtypes among isolates expressing the 6A serotype.

PMID- 16455889
TI  - Occurrence and kinetics of false-positive Aspergillus galactomannan test results
      following treatment with beta-lactam antibiotics in patients with hematological
      disorders.
AB  - Several reports have described a high rate of false-positive Aspergillus
      galactomannan (GM) test results for patients treated with piperacillin
      tazobactam. In this retrospective study, we first examined the relationships
      between intravenous administration of three beta-lactam antibiotics and the
      occurrence of false-positive GM test results in hematology patients. We then
      estimated the kinetics of clearance of GM after the cessation of treatment.
      Sequential serum samples from 69 patients that had received beta-lactams were
      analyzed by using a Platelia Aspergillus test. A significant association was
      found between GM positivity (>/=0.5) and the administration of beta-lactams (P <
      0.0001). The direct role of beta-lactams in patients' serum positivity was
      assessed by testing 39 batches of beta-lactams, of which 27 were positive for GM.
      None of the latter were positive according to a fungus- and Aspergillus-specific
      PCR. The kinetics of the decrease of GM was analyzed on sequential serum samples
      obtained after treatment. By use of a nonlinear regression model, the average
      time to negative antigen was assessed to be 5.5 days (95% confidence interval
      [CI], 4.1 to [7.0]), with a half-life of elimination of GM of 2.4 days (95% CI,
      1.8 to 3.0). This study confirms that the administration of beta-lactams
      containing GM is responsible for false-positive diagnostic results, even up to 5
      days after the cessation of treatment.

PMID- 16455890
TI  - Environmental monitoring for gastroenteric viruses in a pediatric primary
      immunodeficiency unit.
AB  - The aim of this study was to determine if gastroenteric viruses were present on
      surfaces and equipment in a pediatric primary immunodeficiency unit (PPIU) by
      environmental sampling using swabs and subsequent nucleic acid extraction and
      reverse transcriptase PCR assays. A PPIU was chosen, and 11 swabs were taken at
      the same sites every 2 weeks for 6 months. Nested/heminested PCR assays were used
      to screen for astroviruses (AsV), noroviruses (NoV), and rotaviruses (RV). AsV,
      NoV, and RV were detected at multiple swab sites during the study period. NoV was
      the most frequently detected virus on environmental surfaces; however, RV was
      detected on 79% and NoV on 50% of swabbing dates during the study period. Toilet
      taps were the most contaminated sites. Fecal samples from selected patients in
      the unit were also screened during the study period, and patients excreted AsV,
      NoV, and RV at times during the study. New cleaning schedules and changes in some
      of the PPIU sanitary furniture have been suggested as a means of reducing
      environmental contamination.

PMID- 16455891
TI  - High analytical sensitivity and low rates of inhibition may contribute to
      detection of Chlamydia trachomatis in significantly more women by the APTIMA
      Combo 2 assay.
AB  - The clinical sensitivity of nucleic acid amplification tests may be determined by
      analytical sensitivity and inhibitors in patient samples. We established
      endpoints for detection of propagated Chlamydia trachomatis L2 434, diluted
      according to swab and urine protocols for APTIMA Combo 2 (AC2), ProbeTec ET (PT),
      and Amplicor (AMP) assays. AC2 was 1,000-fold more sensitive than PT and 10-fold
      more sensitive than AMP on mock swab specimens. For urine, AC2 analytical
      sensitivity was 100-fold greater than those of the other assays. Spiking an
      aliquot of each clinical-trial sample from 298 women demonstrated inhibition
      rates in first-void urine (FVU), cervical swabs (CS), and vaginal swabs (VS) of
      12.1%, 12.8%, and 10.4% for AMP; 27.2%, 2%, and 2%, for PT; and 0.3%, 1.7%, and
      1.3% for AC2. Inhibition of our C. trachomatis spike and the PT or AMP
      amplification controls from the manufacturers showed less than 50% correlation.
      Using an infected-patient reference standard (a specimen positive in at least two
      tests or a single test positive in two of three samples) in AC2, the VS
      identified 68/69 (98.6%) infected women compared to CS (89.9%) or FVU (81.2%).
      Significantly fewer women were identified by PT (65.2%, 63.8%, and 66.7%) or AMP
      (65.2%, 59.4%, and 56.5%) with the three specimens. By individual specimen type,
      AC2 confirmed virtually all PT- and AMP-positive specimens, but rates of AC2
      confirmation by AMP or PT ranged from 62.9 to 80.3%. The AC2 test identified
      significantly more women infected with C. trachomatis (P = 0.001). Vaginal swabs
      appear to be the specimen of choice for screening.

PMID- 16455892
TI  - Application of pulsed-field gel electrophoresis to identify potential outbreaks
      of campylobacteriosis in New Zealand.
AB  - Since 2002, New Zealand's incidence of campylobacteriosis has exceeded 300 cases
      per 100,000 people per annum. To evaluate genetic variation in human isolates,
      183 Campylobacter isolates were collected from a single clinical laboratory in
      Christchurch: 77 during an 8-week period in spring, and the rest 3 months later
      over a second 8-week period in autumn. Isolates were identified to the species
      level and subtyped using Penner serotyping (Campylobacter jejuni only) and pulsed
      field gel electrophoresis (PFGE) using both SmaI and KpnI. Approximately two
      thirds of the isolates could be grouped into clusters of between 2 and 26
      isolates with indistinguishable SmaI and KpnI patterns. Less than 10% of the
      isolates were of the same type between the two sampling periods. The
      epidemiological relevance of the PFGE clusters was supported by temporal
      clustering, some spatial clustering, and some statistically significant
      demographic similarities among cases in a cluster. Conversely, patient cases
      yielding isolates which did not cluster with isolates from other cases were more
      likely to report recent overseas travel and less likely to live within larger
      urban centers. To identify whether these clusters actually represent common
      source outbreaks, however, would require the detailed, rapid, and reiterative
      epidemiological investigation of cases within a PFGE cluster. The combined and
      timely application of subtyping and epidemiological investigation would appear to
      be a promising strategy for understanding campylobacteriosis in New Zealand.

PMID- 16455893
TI  - Partial nucleotide sequencing of the mecA genes of Staphylococcus aureus isolates
      from cats and dogs.
AB  - Methicillin-resistant staphylococci (MRS) pose a challenge to clinicians and
      health administrators in human medicine, but MRS infections in cats and dogs are
      not perceived as a problem in veterinary medicine. Ten methicillin-resistant
      staphylococcal isolates obtained from healthy and diseased cats and dogs were
      subjected to partial DNA sequencing of the mecA gene. Sequence analysis shows
      that MRS isolates from both healthy and diseased cats and dogs can harbor the
      mecA gene. The mecA genes of animal isolates were identical to that found in
      human MRS strains, and therefore the possibility of zoonotic transfer must be
      considered.

PMID- 16455894
TI  - Comparison of serum hepatitis C virus (HCV) RNA and core antigen levels in
      patients coinfected with human immunodeficiency virus and HCV and treated with
      interferon plus ribavirin.
AB  - Trak-C (Ortho-Clinical Diagnostics) is an enzyme-linked immunosorbent assay-based
      method capable of quantifying hepatitis C virus (HCV) core antigen (CA) in serum
      and could be an alternative to molecular detection and quantification of HCV RNA.
      We have evaluated the Trak-C assay in comparison with an HCV RNA quantitative
      assay (Versant HCV v3.0; Bayer Diagnostics) in the follow-up of 348 treated,
      human immunodeficiency virus (HIV)/HCV-coinfected patients included in the ANRS
      HC02 RIBAVIC trial. ANRS HC02 RIBAVIC is a therapeutic, multicenter, randomized
      protocol comparing the efficacy of alpha interferon 2b (IFN-alpha2b) (3 million
      units three times a week)-ribavirin (800 mg/day) to that of pegylated IFN-alpha2b
      (1.5 mug/kg of body weight/week)-ribavirin (800 mg/day) during 48 weeks of
      treatment of HIV/HCV-coinfected patients naive to HCV treatment. Patients were
      assessed for virological analysis at day 0 and weeks 4, 12, 24, 48, and 72.
      Correlation of HCV RNA and HCV CA at the initiation of treatment was excellent (r
      = 0.92). HCV RNA and CA kinetics were similar during follow-up of HCV treatment
      from day 0 to week 72 whatever the group of response and genotype. The positive
      and negative predictive values of response to the treatment at week 4 were 59 and
      94%, respectively, for HCV RNA load reduction of >2 log and 54 and 94%,
      respectively, for HCV CA below the threshold value (4.18 log(10) pg/ml . 10(4)).
      Trak-C, a new assay able to quantify CA in HIV/HCV-coinfected patients,
      correlates well with quantitative HCV RNA assays and is cheaper and easier to
      perform than molecular technology. HCV CA could be a valuable alternative test
      for therapeutic follow-up of coinfected patients treated with IFN plus ribavirin
      in developing countries.

PMID- 16455895
TI  - Real-time PCR quantification of genital shedding of herpes simplex virus (HSV)
      and human immunodeficiency virus (HIV) in women coinfected with HSV and HIV.
AB  - The accuracy and usefulness of laboratory-developed real-time PCR procedures
      using a Light Cycler instrument (Roche Diagnostics) for detecting and quantifying
      human immunodeficiency virus type 1 (HIV-1) RNA and DNA as well as herpes simplex
      virus type 1 (HSV-1)/HSV-2 DNA in cervicovaginal secretions from women coinfected
      with HIV and HSV were evaluated. For HIV-1, the use of the NEC152 and NEC131
      primer set and the NEC-LTR probe in the long terminal repeat gene allowed us to
      detect accurately the majority of HIV-1 subtypes of group M circulating in sub
      Saharan Africa, including subtypes A, B, C, D, and G as well as circulating
      recombinant forms 02 and 11. The detection threshold of real-time PCR for HIV in
      cervicovaginal lavage samples was 5 copies per assay for both RNA and DNA; the
      intra- and interassay coefficients of variation of C(T) values were 1.30% and
      0.69% (HIV-1 RNA) and 1.84% and 0.67% (HIV-1 DNA), respectively. Real-time PCR
      for HSV using primers and probe targeting the HSV DNA polymerase gene allowed
      both detection and quantification of HSV DNA and also differentiation between HSV
      1 and HSV-2 genotypes. The detection threshold of real-time PCR for HSV was 5
      copies per assay; the intra- and interassay coefficients of variation of C(T)
      values were 0.96% and 1.49%, respectively. Both manual and automated silica-based
      procedures were appropriate for combined extraction of HIV and HSV genomes from
      female genital secretions. Taken together, these findings indicate that real-time
      PCR may be used as a unique nucleic acid amplification procedure to detect and
      quantify HIV and HSV genomes in cervicovaginal secretions and thus to assess at
      reduced costs the genital shedding of both viruses in women included in
      intervention studies.

PMID- 16455896
TI  - Sequencing of hsp65 distinguishes among subsets of the Mycobacterium avium
      complex.
AB  - The Mycobacterium avium complex consists of epidemiologically distinct subsets.
      The classification of these subsets is complicated by a number of factors,
      including the ambiguous results obtained with phenotypic and genetic assays and
      the recent appreciation that human and avian strains appear to be distinct. In
      previous work, sequencing based on a 441-bp portion of the hsp65 gene has proven
      to efficiently classify isolates within the Mycobacterium genus but provides low
      resolution for distinguishing among members of the M. avium complex. Therefore,
      in this study, we have targeted the more variable 3' region of the hsp65 gene to
      determine whether it can effectively discriminate M. avium complex isolates at
      the levels of species and subspecies. Primers designed for this target
      consistently generated amplicons for all organisms classified as M. avium
      complex. Sequences obtained indicate that M. intracellulare is genetically
      divergent from M. avium organisms, and distinct sequevars were obtained for M.
      avium subsets, including M. avium subsp. avium (bird type), M. avium subsp.
      hominissuis, and M. avium subsp. paratuberculosis. In addition, sequence
      differences served to distinguish bovine from ovine strains of M. avium subsp.
      paratuberculosis. A unique profile for M. avium subsp. silvaticum was not
      obtained. These results indicate that sequencing the 3' region of the hsp65 gene
      can simply and unambiguously distinguish species and subspecies of the M. avium
      complex.

PMID- 16455897
TI  - Molecular analysis of an echovirus 3 strain isolated from an individual
      concurrently with appearance of islet cell and IA-2 autoantibodies.
AB  - Growing evidence has implicated members of the genus Enterovirus of the family
      Picornaviridae in the etiology of some cases of type 1 diabetes (T1D). To
      contribute to an understanding of the molecular determinants underlying this
      association, we determined the complete nucleotide sequence of a strain of
      echovirus 3 (E3), Human enterovirus B (HEV-B) species, isolated from an
      individual who soon after virus isolation developed autoantibodies characteristic
      of T1D. The individual has remained positive for over 6 years for tyrosine
      phosphatase-related IA-2 protein autoantibodies and islet cell autoantibodies,
      indicating an ongoing autoimmune process, although he has not yet developed
      clinical T1D. The sequence obtained adds weight to the observation that recent
      enterovirus isolates differ significantly from prototype strains and provides
      further evidence of a role for recombination in enterovirus evolution. In common
      with most HEV-B species members, the isolate exhibits 2C and VP1 sequences
      suggested as triggers of autoimmunity through molecular mimicry. However,
      comparisons with the E3 prototype strain and previously reported diabetogenic and
      nondiabetogenic HEV-B strains do not reveal clear candidates for sequence
      features of PicoBank/DM1/E3 that could be associated with autoantibody
      appearance. This is the first time a virus strain isolated at the time of
      commencement of beta-cell damage has been analyzed and is an invaluable addition
      to enterovirus strains isolated previously at the onset of T1D in the search for
      specific molecular features which could be associated with diabetes induction.

PMID- 16455898
TI  - Use of the espZ gene encoded in the locus of enterocyte effacement for molecular
      typing of shiga toxin-producing Escherichia coli.
AB  - Infections with Shiga toxin-producing Escherichia coli (STEC) result in frequent
      cases of sporadic and outbreak-associated enteric bacterial disease in humans.
      Classification of STEC is by stx genotype (encoding the Shiga toxins), O and H
      antigen serotype, and seropathotype (subgroupings based upon the clinical
      relevance and virulence-related genotypes of individual serotypes). The espZ gene
      is encoded in the locus of enterocyte effacement (LEE) pathogenicity island
      responsible for the attaching and effacing (A/E) lesions caused by various E.
      coli pathogens (but not limited to STEC), and this individual gene (
      approximately 300 bp) has previously been identified as hypervariable among these
      A/E pathogens. Sequence analysis of the espZ locus encoded by additional STEC
      serotypes and strains (including O26:H11, O121:H19, O111:NM, O145:NM, O165:H25,
      O121:NM, O157:NM, O157:H7, and O5:NM) indicated that distinct sequence variants
      exist which correlate to subgroups among these serotypes. Allelic discrimination
      at the espZ locus was achieved using Light Upon eXtension real-time PCR and by
      liquid microsphere suspension arrays. The allele subtype of espZ did not
      correlate with STEC seropathotype classification; however, a correlation with the
      allele type of the LEE-encoded intimin (eae) gene was supported, and these
      sequence variations were conserved among individual serotypes. The study focused
      on the characterization of three clinically significant seropathotypes of LEE
      positive STEC, and we have used the observed genetic variation at a pathogen
      specific locus for detection and subtyping of STEC.

PMID- 16455899
TI  - Use of PCR-restriction fragment length polymorphism analysis to identify the main
      new world Leishmania species and analyze their taxonomic properties and
      polymorphism by application of the assay to clinical samples.
AB  - At least 13 characterized Leishmania species are known to infect humans in South
      America. Five of these parasites are transmitted in the sylvatic ecotopes of the
      whole French Guianan territory and responsible for cutaneous leishmaniasis. For
      the diagnosis of cutaneous leishmaniasis, restriction fragment length
      polymorphism (RFLP) analyses have shown promising results. Thus, the end of the
      small subunit and internal transcribed spacer 1 of the rRNA genes were sequenced
      and targeted by PCR-RFLP analysis in the 10 main New World (NW) Leishmania
      species from the two subgenera. Then, the procedure was tested on 40 samples from
      patients with cutaneous leishmaniasis, and its results were compared with those
      of conventional methods. (i) The results of this simple genus-specific method
      were in agreement with those of previous isoenzyme analyses. (ii) This method
      distinguished the most medically relevant Leishmania species with only one enzyme
      (RsaI). (iii) This method could be performed directly on human biopsy specimens
      (sensitivity of 85.7%). Performing NW Leishmania species typing rapidly and
      easily in the field constitutes a very valuable improvement for detection of
      Leishmania spp. Revealing great diversity with several enzymes, this method could
      also be useful for taxonomic, ecological, and epidemiological studies in space
      and time.

PMID- 16455900
TI  - Molecular epidemiology of Leishmania (Viannia) guyanensis in French Guiana.
AB  - Little information is available about the genetic variability of Leishmania
      populations and the possible correlations with ecoepidemiological features of
      leishmaniases. The present study was carried out in French Guiana, a country
      where cutaneous leishmaniases (CL) are endemic over the whole territory. The
      genetic polymorphism of a nuclear sequence encompassing the end of the ribosomal
      small subunit and the internal transcribed spacer 1 of 265 isolates from patients
      with CL was examined by restriction fragment length polymorphism analysis.
      Genotypes based on the fingerprinting phenetic integration were compared to
      epidemiological, clinical, and geographical data. In agreement with previous
      reports, five different Leishmania species were identified, but Leishmania
      (Viannia) guyanensis represented 95.8% of the samples. Two distinct L. (V.)
      guyanensis populations were found to originate in two ecologically characterized
      regions. Higher lesional parasite densities and the need for additional
      treatments were significantly linked to genotype group I. Parasites of genotype
      group II were more likely to cause chronic and disseminated cutaneous forms in
      patients. L. (V.) guyanensis was previously said not to be very polymorphic;
      however, the present analysis resulted in a significant degree of discrimination
      among L. (V.) guyanensis isolates from diverse ecological areas and with
      different clinical implications.

PMID- 16455901
TI  - Neisseria bacilliformis sp. nov. isolated from human infections.
AB  - Most Neisseria species are gram-negative cocci or diplococci; currently, N.
      elongata is the only species of human origin with a bacillary morphology. Here,
      we report isolation and characterization of eight strains of another bacillary
      Neisseria species from human infections. The organisms caused or contributed to
      either oral cavity-related or respiratory tract infections, and two strains were
      isolated from blood cultures. The 16S rRNA gene sequences of these organisms,
      being homogenous or nearly so (99.4 to 100% identity), matched at <96% known
      Neisseria species and formed a distinct group within the genus. Analysis of the
      cellular fatty acids showed broad similarity with a few Neisseria species. The
      organisms were gram negative and measured 0.6 mum by 1.3 to 3.0 mum. They grew
      well on chocolate agar and on sheep blood agar but did not grow on modified
      Thayer-Martin agar. They were positive for oxidase and negative for indole
      production. There was no acid production from dextrose, lactose, maltose, or
      sucrose. The tests for catalase reaction, nitrate reduction, and tributilin
      varied with the strains. These results suggest that these organisms represent a
      novel species within the genus Neisseria, for which the name Neisseria
      bacilliformis sp. nov. is proposed. The type strain is MDA2833 = ATCC BAA-1200(T)
      = CCUG50858(T). Distinction between N. bacilliformis and N. elongata can be made
      confidently by 16S rRNA gene sequencing or cellular fatty acid profiling but may
      be difficult by morphology or routine biochemical tests.

PMID- 16455902
TI  - Sequence variation of the SeM gene of Streptococcus equi allows discrimination of
      the source of strangles outbreaks.
AB  - Improved understanding of the epidemiology of Streptococcus equi transmission
      requires sensitive and portable subtyping methods that can rationally
      discriminate between strains. S. equi is highly homogeneous and cannot be
      distinguished by multilocus enzyme electrophoretic or multilocus sequence-typing
      methods that utilize housekeeping genes. However, on sequence analysis of the N
      terminal region of the SeM genes of 60 S. equi isolates from 27 strangles
      outbreaks, we identified 21 DNA codon changes. These resulted in the
      nonsynonymous substitution of 18 amino acids and allowed the assignment of S.
      equi strains to 15 distinct subtypes. Our data suggest the presence of multiple
      epitopes across this region that are subjected to selective immune pressure
      (nonsynonymous-synonymous substitution rate [d(N)/d(S)] ratio = 3.054),
      particularly during the establishment of long-term S. equi infection. We further
      report the application of SeM gene subtyping as a method to investigate potential
      cases of disease related to administration of a live attenuated S. equi vaccine.
      SeM gene subtyping successfully differentiated between the vaccine strain and
      field strains of S. equi responsible for concurrent disease. These results were
      confirmed by the development and application of a PCR diagnostic test, which
      identifies the aroA partial gene deletion present in the Equilis StrepE vaccine
      strain. Although the vaccine strain was found to be responsible for injection
      site lesions, all seven outbreaks of strangles investigated in recently
      vaccinated horses were found to be due to concurrent infection with wild-type S.
      equi and not due to reversion of the vaccine strain.

PMID- 16455903
TI  - Genotyping measles virus by real-time amplification refractory mutation system
      PCR represents a rapid approach for measles outbreak investigations.
AB  - Real-time PCR has been developed to genotype measles virus (MV) isolates. MV
      strains circulating in epidemics in Gabon in 1984, Cameroon in 2001, Morocco in
      2003, and France in 2004 were investigated. We developed a real-time
      amplification refractory mutation system PCR (RT-AMRS PCR) using SYBR green
      fluorescent dye. Six pairs of primers for RT-ARMS PCR were designed to
      specifically amplify genotypes A, B2, B3.1, B3.2, C2, and D7. Genotypes could be
      differentiated by melting curve analysis. All strains were also confirmed by
      direct sequencing. Using the result obtained by direct sequencing and
      phylogenetic analysis as the reference, the accuracy of MV by RT-ARMS PCR and
      melting curve analysis was 97%. However, the latter method is more rapid and
      sensitive than the former method. This method could be a useful tool for
      molecular epidemiological studies of MV, providing an efficient alternative for
      large-scale studies.

PMID- 16455904
TI  - Multilocus microsatellite typing as a new tool for discrimination of Leishmania
      infantum MON-1 strains.
AB  - The Leishmania donovani complex, which consists of L. donovani, L. infantum-L.
      chagasi, and L. archibaldi, is responsible for visceral manifestations of
      leishmaniasis. Multilocus enzyme electrophoresis is the standard method for the
      characterization and identification of strains of Leishmania. For L. infantum,
      the predominance of zymodeme MON-1 significantly reduces the discriminative power
      of this approach. In the present study, we developed 17 independent polymorphic
      microsatellite markers for the typing of strains of L. infantum, with the main
      emphasis on zymodeme MON-1. The discriminative powers of 11 markers selected from
      among these markers were tested by using a panel of 63 isolates of the L.
      donovani complex. Unique multilocus genotypes were observed for the strains
      analyzed, with only three exceptions. Model-based and distance-based analyses of
      the data set showed comparable results. It was possible to discriminate between
      L. donovani sensu stricto, a non-MON-1 group of L. infantum isolates, and a MON-1
      group of L. infantum isolates. Within MON-1, three clusters with geographical
      correlations became apparent. The frequency of heterozygosity in the alleles
      analyzed varied extremely between the different groups of isolates. The main
      clusters described are not consistent with species definitions based on isoenzyme
      analysis but confirm the results of former PCR-based investigations.

PMID- 16455905
TI  - Bead-based multiplex genotyping of human papillomaviruses.
AB  - Typing of human papillomaviruses (HPV) by DNA hybridization procedures, such as
      reverse line blot (RLB) assay, is sensitive and well validated. However, the
      application of these assays to high-throughput analyses is limited. Here, we
      describe the development of multiplex human papillomavirus genotyping (MPG), a
      quantitative and sensitive high-throughput procedure for the identification of
      multiple high- and low-risk genital HPV genotypes in a single reaction. MPG is
      based on the amplification of HPV DNA by a general primer PCR (GP5+/6+) and the
      subsequent detection of the products with type-specific oligonucleotide probes
      coupled to fluorescence-labeled polystyrene beads (Luminex suspension array
      technology). Up to 100 different HPV types can be detected simultaneously with
      MPG, and the method is fast and labor saving. We detected all 22 HPV types
      examined with high specificity and reproducibility (the median interplate
      coefficient of variation was below 10%). Detection limits for the different HPV
      types varied between 100 and 800 pg of PCR products. We compared the performance
      of MPG to an established RLB assay on GP5+/6+-PCR products derived from 94
      clinical samples. The evaluation showed an excellent agreement (kappa = 0.922)
      but also indicated a higher sensitivity of MPG. In conclusion, MPG appears to be
      highly suitable for large-scale epidemiological studies and vaccination trials as
      well as for routine diagnostic purposes.

PMID- 16455906
TI  - Comparison of physician- and self-collected genital specimens for detection of
      human papillomavirus in men.
AB  - There is currently no consensus regarding the most appropriate methods of
      sampling for the detection of genital human papillomavirus (HPV) in men. We
      employed a recently developed collection method involving abrasion and moistened
      swabbing of the genital skin surface for the detection of HPV in a cohort of 136
      university-affiliated males in Hawaii. Genital specimens collected by physicians
      using this method were compared with self-collected specimens from the same
      individuals obtained 24 h later. Self-collected specimens yielded a greater
      proportion of sufficient specimens than physician-collected specimens. HPV
      detection was comparable in physician- and self-collected specimens; detection
      was highest in the penile shaft (51.2% and 51.5%, respectively, P = 0.96),
      followed by the scrotum (41.2% and 46.2%, P = 0.43), the glans/coronal sulcus
      (31.9% and 33.1%, P = 0.84), and the foreskin (33.3% and 28.6%, P = 0.74). Site
      specific agreement in HPV detection between paired physician- and self-collected
      samples ranged from 67.2% (kappa = 0.34) for the penile shaft to 95.0% (kappa =
      0.89) for the foreskin. There was a high degree of concordance in HPV genotypes
      in HPV-positive pairs. The most common type was HPV type 84, which comprised
      approximately 15% of the specimens. The emery paper-swab method offers an
      efficient sampling method for genital HPV DNA detection in men that could be used
      both within and outside of the clinical setting.

PMID- 16455907
TI  - Extensive hospital-wide spread of a multidrug-resistant enterobacter cloacae
      clone, with late detection due to a variable antibiogram and frequent patient
      transfer.
AB  - A hospital-wide increase in the number of patients with aminoglycoside-resistant
      Enterobacter cloacae (AREC) isolated from clinical cultures was detected in
      December 2002 using a classical surveillance system (CSS). CSS refers to a
      strategy based on the recognition of an increased incidence of a species with a
      particular antibiogram at certain wards in a limited period. Since clonal spread
      was suspected, hospital records were reviewed for E. cloacae culture-positive
      patients. Based upon genotyping of 139 clinical E. cloacae isolates from 80
      patients, it was concluded that 53 patients had had clinical cultures with a
      single AREC clone since April 2001. Determinants for unnoticed spread were
      investigated retrospectively, as was the possibility that a computer-assisted
      surveillance method would have detected this outbreak at an earlier stage.
      Determinants associated with late detection of clonal spread were the following:
      (i) the absence of a hospital-wide increase in incidence of E. cloacae cases for
      1.5 years, (ii) the long time interval between cases, (iii) the hospital-wide
      occurrence of new cases, due to a high number of patient transfers between wards,
      (iv) the large variety of clinical sites, and (v) the high variability of
      antibiograms (n = 33). Retrospective application of a recently described computer
      assisted surveillance method as well as an "in-house"-developed algorithm
      resulted in earlier detection of the outbreak of 6 and 12 months, respectively.
      These findings suggest that computerized tools for surveillance may recognize
      resistance trends that are too complex to be detected by manual review and
      indicate the need for prospective evaluation of such algorithms.

PMID- 16455908
TI  - Nasopharyngeal versus oropharyngeal sampling for isolation of potential
      respiratory pathogens in adults.
AB  - The optimal methodology for the identification of colonization by potential
      respiratory pathogens (PRP) in adults is not well established. The objectives of
      the present study were to compare the sensitivities of sampling the nasopharynx
      and the oropharynx for identification of PRP colonization and to compare the
      sensitivities of samples from the nasopharynx by swab and by washing for the same
      purpose. The study included 500 participants with a mean age of 65.1 +/- 17.8
      years. Of these, 300 patients were hospitalized for acute febrile lower
      respiratory tract infection and 200 were controls. Each participant was sampled
      by oropharyngeal swab (OPS), nasopharyngeal swab (NPS), and nasopharyngeal
      washing (NPW). The samples were tested by conventional bacteriological methods to
      identify Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
      catarrhalis. OPS detected colonization by S. pneumoniae in 30% of the subjects
      compared with 89% by NPS and NPW (P < 0.000001). The corresponding rates for H.
      influenzae were 49% and 64%, respectively (no significant difference [NS]), and
      for M. catarrhalis were 72% and 46%, respectively (P < 0.0004). NPS identified
      61% of the cases of colonization with S. pneumoniae, compared with 76% by NPW
      (NS). The corresponding rates for H. influenzae were 31% and 56%, respectively (P
      < 0.04), and for M. catarrhalis were 39% and 33%, respectively (NS). We conclude
      that the sensitivities of nasopharyngeal and oropharyngeal sampling for
      identification of PRP colonization in adults are different for each of the three
      bacteria in this category. The combined results of sampling from both sites are
      necessary to obtain a true picture of the rate of colonization. NPW is superior
      to NPS.

PMID- 16455909
TI  - Triazole cross-resistance among Candida spp.: case report, occurrence among
      bloodstream isolates, and implications for antifungal therapy.
AB  - Candida spp. are common causes of bloodstream infections among hospitalized
      patients. Fluconazole (FLC) remains a first-line therapy for candidemia; and
      voriconazole (VRC), an expanded-spectrum triazole, was recently approved for the
      treatment of candidemia in nonneutropenic patients. In vitro studies have
      suggested that VRC has potent activity against Candida spp. with reduced
      susceptibilities to FLC. We present a case report of invasive candidiasis and
      candidemia due to a Candida glabrata isolate that developed resistance to all
      currently available triazole antifungals after a course of FLC treatment. This
      case prompted us to determine the frequency of cross-resistance among bloodstream
      Candida isolates collected during a recent 12-month period at a large, academic
      medical center. FLC MICs were determined for 125 of 153 isolates (81.7%). Thirty
      of 125 isolates (24%) were resistant or showed reduced susceptibilites to FLC
      (MICs >/= 16 microg/ml). When 28 of these 30 isolates were tested for their VRC
      susceptibilities, 9 (32%) had MICs that were >/=2 microg/ml. Five of these nine
      isolates were C. glabrata, two isolates were Candida tropicalis, one isolate was
      Candida albicans, and one isolate was Candida parapsilosis. All five Candida
      krusei isolates tested had VRC MICs </=0.5 microg/ml. These data have prompted
      the introduction of reflexive FLC susceptibility testing of first bloodstream
      Candida isolates at our institution. The case report and our data also suggest
      that VRC should be avoided as initial therapy in unstable patients with invasive
      candidiasis, particularly in the setting of prior azole exposure. Studies are
      needed to define the clinical significance of in vitro resistance to the newer
      antifungal agents.

PMID- 16455910
TI  - Use of PCR-restriction enzyme pattern analysis and sequencing database for hsp65
      gene-based identification of Nocardia species.
AB  - Nocardia identification required laborious and time-consuming phenotypic and
      chemotaxonomic methods until molecular methods were developed in the mid-1990s.
      Here we reassessed the capacity of PCR-restriction enzyme pattern analysis (PRA)
      of the hsp65 gene to differentiate Nocardia species, including 36 new species.
      Our results confirm that hsp65 PRA must no longer be used for Nocardia species
      identification, as many species have the same restriction pattern. We then
      compared sequencing-based strategies using an hsp65 database and a 16S rRNA
      database and found that the hsp65 region contained sufficient polymorphisms for
      comprehensive Nocardia species identification.

PMID- 16455911
TI  - Recovering streptococci from the throat, a practical alternative to direct
      plating in remote tropical communities.
AB  - Throat swabs are regarded as the "gold standard" for diagnosing streptococcal
      pharyngitis and for surveillance research. Culturing throats in remote tropical
      settings is logistically difficult, and these settings are commonly burdened by
      high rates of streptococcal disease. The survival of streptococci on swabs may
      depend on whether they are of "throat" or "skin" type, as determined by emm
      pattern typing. The aims of this study were to compare the recovery rates of beta
      hemolytic streptococci (BHS) using three different transport methods and to
      determine whether the recovery rates correlated with the emm pattern type.
      Monthly duplicate throat swabs were taken from occupants of selected households
      in three remote Aboriginal communities. Paired swabs were separated and handled
      in one of three ways: (i) direct inoculation onto culture media with cold-box
      transport (plated), (ii) sealed in a bag with a silica gel desiccant and cold-box
      transport (desiccant), and (iii) transport at ambient temperature and humidity
      (ambient). emm pattern typing was done by standard methods. Over 23 months, 4,842
      throat swabs were taken, and 4,122 were paired. BHS were recovered on 11.5% of
      the 4,842 occasions (group A, 4.5%; group C, 1.7%; group G, 5.4%). Results from
      paired swabs showed the plated method was superior to desiccant and desiccant was
      better than ambient. Pooled data indicated that plated and desiccant were
      equivalent, and both were significantly better than ambient. There was no
      correlation between the emm pattern type and recovery of group A streptococci by
      different methods. In tropical and remote settings, cold-box transport with
      desiccant and subsequent inoculation of culture plates in the laboratory is a
      practical alternative to direct plating.

PMID- 16455912
TI  - Rapid susceptibility testing of medically important zygomycetes by XTT assay.
AB  - The XTT colorimetric assay quantifies fungal growth by measuring fungal
      metabolism and has been used successfully for susceptibility testing of
      Aspergillus species after 24 and 48 h of incubation. In the present study using
      14 clinical isolates of Zygomycetes (Rhizopus oryzae [5 isolates], Cunninghamella
      spp. [3 isolates], Mucor spp. [3 isolates], and Absidia corymbifera [3
      isolates]), significant metabolic activity was demonstrated before visual or
      spectrophotometric detection of fungal growth by performing the XTT assay as
      early as 6 h after inoculation. Testing of susceptibility to amphotericin B,
      posaconazole, and voriconazole was subsequently performed using the XTT method
      (100 microg/ml XTT, 25 microM menadione) at 6, 8, or 12 h after inoculation and
      the CLSI (formerly NCCLS) M38-A method with visual and spectrophotometric MIC
      determinations at 24 h after inoculation. Concentration-effect curves obtained
      with the use of the E(max) model (a sigmoid curve with variable slope) were
      comparable between the early XTT and spectrophotometric readings at 24 h.
      Complete inhibition of early metabolic activity with the azoles was delayed in
      comparison to that with amphotericin B. Using appropriate cutoff levels,
      agreement was demonstrated between the early XTT and 24-h spectrophotometric or
      visual readings. In particular, for MIC-0 (the lowest drug concentration showing
      absence of visual growth) of amphotericin B, overall agreement levels were 90 to
      93% for the 6-h XTT assay and 100% for the 8- and 12-h time points. For MIC-0 of
      posaconazole, agreement levels were 86% for the 6-h XTT and 93 to 100% for the 8-
      and 12-h time points. The overall agreement levels for MIC-0 and MIC-2 (the
      lowest drug concentration showing prominent reduction of growth compared with the
      control well) of voriconazole (compared with 24-h spectrophotometric readings)
      were 93 to 98% for the 8- and 12-h XTT assays. These results support the use of
      the XTT method for rapid MIC determination for Zygomycetes.

PMID- 16455913
TI  - Use of electrochemical DNA biosensors for rapid molecular identification of
      uropathogens in clinical urine specimens.
AB  - We describe the first species-specific detection of bacterial pathogens in human
      clinical fluid samples using a microfabricated electrochemical sensor array. Each
      of the 16 sensors in the array consisted of three single-layer gold electrodes
      working, reference, and auxiliary. Each of the working electrodes contained one
      representative from a library of capture probes, each specific for a clinically
      relevant bacterial urinary pathogen. The library included probes for Escherichia
      coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterocococcus spp., and the
      Klebsiella-Enterobacter group. A bacterial 16S rRNA target derived from single
      step bacterial lysis was hybridized both to the biotin-modified capture probe on
      the sensor surface and to a second, fluorescein-modified detector probe.
      Detection of the target-probe hybrids was achieved through binding of a
      horseradish peroxidase (HRP)-conjugated anti-fluorescein antibody to the detector
      probe. Amperometric measurement of the catalyzed HRP reaction was obtained at a
      fixed potential of -200 mV between the working and reference electrodes. Species
      specific detection of as few as 2,600 uropathogenic bacteria in culture,
      inoculated urine, and clinical urine samples was achieved within 45 min from the
      beginning of sample processing. In a feasibility study of this amperometric
      detection system using blinded clinical urine specimens, the sensor array had
      100% sensitivity for direct detection of gram-negative bacteria without nucleic
      acid purification or amplification. Identification was demonstrated for 98% of
      gram-negative bacteria for which species-specific probes were available. When
      combined with a microfluidics-based sample preparation module, the integrated
      system could serve as a point-of-care device for rapid diagnosis of urinary tract
      infections.

PMID- 16455914
TI  - Results of the first World Health Organization international collaborative study
      of detection of human papillomavirus DNA.
AB  - Twenty-nine laboratories in 12 countries participated in a study to assess the
      performance of various human papillomavirus (HPV) detection assays through the
      use of a recombinant HPV DNA standard reagent panel. The panel was designed by a
      group of HPV experts, and samples were prepared and distributed by the World
      Health Organization International Laboratory for Standards and Biologicals in The
      Netherlands. Each panel consisted of 24 coded samples including a dilution series
      for HPV types 16 and 18, alone or in combination with five other high-risk (HR)
      HPV types including HPV types 31, 33, 35, 45, and 52, the low-risk HPV type 6,
      and a negative control. Qualitative assays were generally consistent across
      laboratories, and most invalid results reflected a lack of HPV test sensitivity.
      The combined data sets had a proficiency for HPV 16 of 62.5% (15/24) and for HPV
      18 of 73.9% (17/23). HPV 31 was the least accurately detected by participating
      laboratories. Approximately half of participating laboratories failed to detect
      high concentrations of HPV 31 and, to a lesser extent, to detect HPV types 35,
      52, and 6. The panel sample materials offer a source of renewable and
      reproducible material that could be used in the future development of
      international standard reagents for calibration of HPV DNA assays and kits.

PMID- 16455915
TI  - Two new colorimetric methods for early detection of vancomycin and oxacillin
      resistance in Staphylococcus aureus.
AB  - We developed two colorimetric methods for the detection of vancomycin- and
      oxacillin-resistant Staphylococcus aureus in </=6 h: (i) a nitrate reductase
      assay and (ii) a resazurin microplate method. MICs agreed with results obtained
      by CLSI methods for oxacillin. However, detection of vancomycin resistance
      required a larger inoculum. These methods may be recommended for the detection of
      vancomycin- and oxacillin-resistant S. aureus.

PMID- 16455916
TI  - Use of different stains for microscopic evaluation of corneal scrapings for
      diagnosis of microsporidial keratitis.
AB  - Retrospective evaluation of potassium hydroxide plus calcofluor white (KOH+CFW),
      Gram, Giemsa, and modified Ziehl-Neelsen (1% H(2)SO(4), cold) stains for the
      detection of microsporidia in corneal scrapings from 30 patients showed KOH+CFW
      and acid-fast stains to be most efficient (29/30 [96.7%] and 28/30 [93.3%],
      respectively) in the diagnosis of microsporidial keratitis.

PMID- 16455917
TI  - Performance of MRSA ID, a new chromogenic medium for detection of methicillin
      resistant Staphylococcus aureus.
AB  - MRSA ID was evaluated for its ability to identify methicillin-resistant
      Staphylococcus aureus. A well-defined collection of staphylococci was used (n =
      998). The sensitivity after 24 h was 96.4%, increasing to 98.8% after 48 h. The
      specificity was 98.2% after 24 h and decreased to 89.7% after 48 h.

PMID- 16455918
TI  - Identification of Cpgp40/15 Type Ib as the predominant allele in isolates of
      Cryptosporidium spp. from a waterborne outbreak of gastroenteritis in South
      Burgundy, France.
AB  - Cryptosporidium sp. isolates from a waterborne outbreak of diarrhea in France
      were analyzed by PCR-restriction fragment length polymorphism analysis and
      sequencing of the Cpgp40/15 locus. Ninety-one percent of the isolates were
      Cryptosporidium hominis type Ib. The results of this study and those of studies
      of other outbreaks suggest that the type Ib allele is the predominant allele
      associated with waterborne cryptosporidiosis.

PMID- 16455919
TI  - Use of cefoxitin-based selective broth for improved detection of methicillin
      resistant Staphylococcus aureus.
AB  - A cefoxitin-based selective broth was evaluated for its efficiency in detecting
      methicillin-resistant Staphylococcus aureus (MRSA) by the use of laboratory
      reference strains, clinical isolates of different clones, and clinical samples.
      The cefoxitin-based broth was proved to be more sensitive and rapid for the
      detection of MRSA strains, especially heterogeneously resistant strains, than the
      oxacillin-based broth.

PMID- 16455920
TI  - Emergence of a clinical daptomycin-resistant Staphylococcus aureus isolate during
      treatment of methicillin-resistant Staphylococcus aureus bacteremia and
      osteomyelitis.
AB  - The emergence of a clinically daptomycin-resistant Staphylococcus aureus isolate
      occurred during treatment of methicillin-resistant S. aureus bacteremia and
      probable vertebral osteomyelitis. The breakthrough isolate was indistinguishable
      from pretreatment daptomycin-susceptible isolates by pulsed-field gel
      electrophoresis. Daptomycin nonsusceptibility was confirmed by MIC and time-kill
      curve analyses.

PMID- 16455921
TI  - Proximal region of the gene encoding cytadherence-related protein permits
      molecular typing of Mycoplasma genitalium clinical strains by PCR-restriction
      fragment length polymorphism.
AB  - Restriction fragment length polymorphism (RFLP) analysis of the PCR-amplified
      proximal region of the gene encoding cytadherence accessory protein P110 (MG192)
      revealed DNA sequence divergences among 54 Mycoplasma genitalium clinical strains
      isolated from the genitourinary tracts of women attending a sexually transmitted
      disease-related health clinic, plus one from the respiratory tract and one from
      synovial fluid. Seven of 56 (12.5%) strains exhibited RFLPs following digestion
      of the proximal region with restriction endonuclease MboI or RsaI, or both. No
      sequence variability was detected in the distal portion of the gene.

PMID- 16455922
TI  - Sequence variability of human erythroviruses present in bone marrow of Brazilian
      patients with various parvovirus B19-related hematological symptoms.
AB  - The presence of erythrovirus infections was investigated by PCR with bone marrow
      samples of patients with various parvovirus B19-related hematological symptoms.
      Erythrovirus DNA was found in 17.3% (12/69) of patients. Phylogenetic analysis
      revealed that five strains cluster with genotype 1, one clusters with genotype 2,
      and six cluster with genotype 3. Our study is the first to document the presence
      of the three erythrovirus genotypes in Brazil.

PMID- 16455923
TI  - Use of a new dual-antigen enzyme-linked immunosorbent assay to detect and
      characterize the human antibody response to the human immunodeficiency virus type
      2 envelope gp125 and gp36 glycoproteins.
AB  - A dual-antigen enzyme-linked immunosorbent assay specific for human
      immunodeficiency virus type 2 (HIV-2) envelope proteins, ELISA-HIV2, was
      developed with two new recombinant polypeptides, rpC2-C3 and rgp36, derived from
      the HIV-2 envelope. The diagnostic performance was determined with HIV-2, HIV-1,
      and HIV-1/2 samples. Both polypeptides showed 100% specificity. Clinical
      sensitivity was 100% for rgp36 and 93.4% for rpC2-C3. ELISA-HIV2 may be used for
      the specific diagnosis and confirmation of HIV-2 infection.

PMID- 16455924
TI  - False-positive amplified Mycobacterium tuberculosis direct test results for
      samples containing Mycobacterium leprae.
AB  - Nucleic acid amplification tests are widely used in mycobacteriology laboratories
      to rapidly detect Mycobacterium tuberculosis complex directly in clinical
      specimens. A positive result provides an early diagnosis of tuberculosis,
      allowing initiation of appropriate therapy and public health measures.

PMID- 16455925
TI  - Unique NS5b hepatitis C virus gene sequence consensus database is essential for
      standardization of genotype determinations in multicenter epidemiological
      studies.
AB  - A multicenter study of NS5b hepatitis C virus (HCV) genotype determination
      involving 12 laboratories demonstrates that any laboratory with expertise in
      sequencing techniques would be able to provide a reliable HCV genotype for
      clinical and epidemiological purposes as long as they are provided a consensus
      reference sequence database.

PMID- 16455926
TI  - Use of commercially available cryogenic vials for long-term preservation of
      dermatophyte fungi.
AB  - The use of commercially available cryogenic vials (Microbank vials) stored at -70
      degrees C for the storage and preservation of dermatophyte fungi was
      investigated. None of the 200 strains of dermatophytes examined, representing 21
      species, showed a loss of viability after they had been stored for periods
      ranging from 1 week to 2 years at -70 degrees C. All strains showed typical
      colonial and microscopic morphologies following revival.

PMID- 16455927
TI  - High interlaboratory reproducibility of DNA sequence-based typing of bacteria in
      a multicenter study.
AB  - Current DNA amplification-based typing methods for bacterial pathogens often lack
      interlaboratory reproducibility. In this international study, DNA sequence-based
      typing of the Staphylococcus aureus protein A gene (spa, 110 to 422 bp) showed
      100% intra- and interlaboratory reproducibility without extensive harmonization
      of protocols for 30 blind-coded S. aureus DNA samples sent to 10 laboratories.
      Specialized software for automated sequence analysis ensured a common typing
      nomenclature.

PMID- 16455928
TI  - Use of molecular beacon probes for real-time PCR detection of Plasmodium
      falciparum and other plasmodium species in peripheral blood specimens.
AB  - We describe the development and evaluation of a novel pair of real-time,
      fluorescence-based PCR assays using molecular beacon probes for rapid, sensitive,
      and specific detection and quantification of Plasmodium falciparum and other
      Plasmodium species organisms.

PMID- 16455929
TI  - Use of PCR to demonstrate presence of adenovirus species B, C, or F as well as
      coinfection with two adenovirus species in children with flu-like symptoms.
AB  - Adenovirus (AdV) respiratory infections have usually been associated with species
      B, C, and E. In this study, we detected 9.4% of AdVs by PCR in 500 nasal swabs
      from 319 children with influenza-like symptoms. AdV typing by PCR with specific
      probes showed species C, B, and F as well as coinfection with two species.
      Coinfection with two AdV species and the presence of species F in respiratory
      samples are novel findings that should be further investigated.

PMID- 16455930
TI  - Sonication of explanted prosthetic components in bags for diagnosis of prosthetic
      joint infection is associated with risk of contamination.
AB  - Explanted orthopedic implants from 54 patients with aseptic failure and 24
      patients with prosthetic knee or hip infection were sonicated in polyethylene
      bags. The sensitivities of periprosthetic tissue and sonicate fluid cultures for
      the diagnosis of prosthetic joint infection were 54% and 75%, whereas the
      specificities were 98% and 87%, respectively. Sonication in bags improved
      bacterial recovery from the surface of orthopedic implants; however, it lacked
      specificity, due to bag leakage.

PMID- 16455931
TI  - Multilocus genotyping of Cryptosporidium sp. isolates from human immunodeficiency
      virus-infected individuals in South India.
AB  - This study characterized cryptosporidial infections in 48 human immunodeficiency
      virus-infected individuals in India by multilocus genotyping. Cryptosporidium
      hominis, C. parvum, C. felis, C. muris, and C. meleagridis were identified.
      Cpgp40/15 PCR-restriction fragment length polymorphism identified six
      subgenotypes. Cryptosporidial diarrhea was associated with decreased CD4 counts,
      below 200 (P = 0.009), but not high viral loads.

PMID- 16455932
TI  - Absence of Helicobacter pylori within the oral cavities of members of a healthy
      South African community.
AB  - Our study aimed to evaluate the oral cavity as a reservoir from where
      Helicobacter pylori may be transmitted. Histology and PCR amplification were
      performed. Eighty-four percent of the stomach biopsies tested positive; however,
      H. pylori was not detected in dental samples, indicating the absence of H. pylori
      within the oral cavity.

PMID- 16455933
TI  - Prospective comparison of a new chromogenic medium, MRSASelect, to CHROMagar MRSA
      and mannitol-salt medium supplemented with oxacillin or cefoxitin for detection
      of methicillin-resistant Staphylococcus aureus.
AB  - MRSASelect agar was compared to CHROMagar, mannitol-salt agar with oxacillin, and
      mannitol-salt agar with cefoxitin (MSA-CFOX) for the isolation of methicillin
      resistant Staphylococcus aureus (MRSA). The sensitivities and specificities were
      97.3% and 99.8%, 82.9% and 99.1%, 80.2% and 79%, and 99.1% and 84.8%,
      respectively. MSA-CFOX and MRSASelect had a high sensitivity. MRSASelect,
      however, was more specific and proved to be a more reliable and rapid medium for
      the detection of MRSA.

PMID- 16455934
TI  - Detection of six copies of the capsulation b locus in a Haemophilus influenzae
      type b strain isolated from a splenectomized patient with fulminant septic shock.
AB  - We report on the first detection of six copies of the capsulation b locus in a
      Haemophilus influenzae type b strain isolated from a splenectomized patient with
      fulminant septic shock associated with disseminated intravascular coagulation and
      death. The unusual amplification of the locus might have contributed to the rare
      and severe clinical presentation.

PMID- 16455935
TI  - Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to
      respiratory tract samples.
AB  - Respiratory culture and multiplex PCR for Streptococcus pneumoniae, Haemophilus
      influenzae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae were applied to
      sputum, nasopharyngeal swabs, and nasopharyngeal aspirates from 235 adult
      patients with community-acquired pneumonia and 113 controls. Both culture and
      multiplex PCR performed well with the different samples and appear to be useful
      as diagnostic tools.

PMID- 16455936
TI  - Timely diagnosis of disseminated toxoplasmosis by sputum examination.
AB  - The diagnosis of disseminated toxoplasmosis in a 14-year-old allogeneic bone
      marrow recipient with graft-versus-host disease was determined by the detection
      of Toxoplasma gondii tachyzoites in sputum smears. Sputum analysis is a valuable
      alternative in the clinical assessment of pulmonary toxoplasmosis, especially
      when conventional invasive techniques are not practicable.

PMID- 16455937
TI  - Capnocytophaga canimorsus mycotic abdominal aortic aneurysm: why the mailman is
      afraid of dogs.
AB  - We describe the first case report of a mycotic abdominal aortic aneurysm
      secondary to Capnocytophaga canimorsus in an immunocompetent 65-year-old man. The
      exposure occurred after his dog scratched his arm and subsequently licked the
      wound. A review of C. canimorsus, a rarely pathogenic but potentially devastating
      bacterium, is also presented.

PMID- 16455938
TI  - Urosepsis with Actinobaculum schaalii and Aerococcus urinae.
AB  - Actinobaculum was isolated from urine only after prolonged incubation in 5% CO(2)
      after discrepancy between urine Gram stain and initial culture results was
      observed. Additional patients were diagnosed using this method. The prevalence of
      Actinobaculum species in urinary tract infections is underestimated since it is
      not isolated by routine urine culture procedures.

PMID- 16455939
TI  - Treatment failure resulting from resistance of Staphylococcus aureus to
      daptomycin.
AB  - Daptomycin, a new cyclic lipopeptide, was recently approved for the treatment of
      infections by gram-positive organisms, including infections with methicillin
      resistant Staphylococcus aureus (MRSA). A patient infected with infected with
      MRSA developed resistance to daptomycin after prolonged exposure, which resulted
      in clinical failure. Clinicians should be aware of the possibility of daptomycin
      resistance and should consider routine testing for daptomycin susceptibility.

PMID- 16455940
TI  - Endocarditis caused by Cardiobacterium valvarum.
AB  - A fastidious, gram-negative bacterium was isolated from the blood of a 51-year
      old man who had acute infectious endocarditis (IE). Characterization of the
      organism through phenotypic and genotypic analyses revealed the causative role of
      Cardiobacterium valvarum. This is the third reported case of IE caused by C.
      valvarum.

PMID- 16455941
TI  - Unilateral empyema as a complication of infectious mononucleosis: a pathogenic
      variant of Lemierre's syndrome.
AB  - We present a case of a healthy 19-year-old female who developed infectious
      mononucleosis complicated by unilateral empyema.

PMID- 16455942
TI  - Group o human immunodeficiency virus type 1 infection that escaped detection in
      two immmunoassays.
AB  - We report a case of human immunodeficiency virus type 1 group O infection not
      detected by two highly sensitive immunoassays. The sera were strongly reactive to
      the V3 peptide of group O but not to the gp41 immunodominant epitope. Gp41 was
      sequenced, confirming that this virus belonged to group O.

PMID- 16455943
TI  - Neonatal mortality in puppies due to bacteremia by Streptococcus dysgalactiae
      subsp. dysgalactiae.
AB  - We report a case of bacteremia in puppies caused by Streptococcus dysgalactiae
      subsp. dysgalactiae. Identification was achieved by phenotypic and molecular
      genetic methods. This is the first report of the recovery of S. dysgalactiae
      subsp. dysgalactiae from dogs.

PMID- 16455944
TI  - Direct detection of Cardiobacterium hominis in serum from a patient with
      infective endocarditis by broad-range bacterial PCR.
AB  - Bacterial DNA was detected directly in the serum of a patient with endocarditis
      by broad-range 16S rRNA PCR followed by sequencing and analysis of the results by
      the BLAST search. Using these methods, Cardiobacterium hominis was identified in
      2 days from the date of serum collection. The microorganism was also isolated and
      identified using conventional methods (bacterial culture and biochemical tests)
      17 days from the date of sample collection. This is the first report showing the
      direct detection of C. hominis in a patient's serum using molecular-based
      methods, emphasizing their potential usefulness as additional and rapid
      diagnostic tools for the detection and identification of fastidious bacteria.

PMID- 16455945
TI  - De novo daptomycin nonsusceptibility in a clinical isolate.

PMID- 16455946
TI  - Mustard seed agar, a new medium for differentiation of Cryptococcus neoformans.

PMID- 16455947
TI  - STAT5-induced self-renewal and impaired myelopoiesis of human hematopoietic
      stem/progenitor cells involves down-modulation of C/EBPalpha.
AB  - Previously, we demonstrated that enforced activation of signal transducer and
      activator of transcription 5 (STAT5A) in human cord blood (CB)-derived
      stem/progenitor cells results in enhanced self-renewal and impaired myelopoiesis.
      The present study identifies C/EBPalpha as a critical component that is down
      regulated by STAT5. Microarray and reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis on STAT5A(1*6)-transduced CD34(+) cells identified
      C/EBPalpha as the most prominently down-regulated gene. To determine the cell
      biological relevance of these observations, a 4-OHT-inducible C/EBPalpha-ER
      protein was co-expressed with the STAT5A(1*6) mutant in CB CD34(+) cells using a
      retroviral approach. Re-expression of C/EBPalpha in STAT5A(1*6) cells resulted in
      a marked restoration of myelopoiesis. The proliferative advantage imposed on
      CD34(+) cells by STAT5A(1*6) depended on the down-modulation of C/EBPalpha, as
      reintroduction of C/EBPalpha induced a quick cell-cycle arrest and the onset of
      myeloid differentiation. Long-term culture-initiating cell (LTC-IC) frequencies
      were elevated from 0.8% +/- 0.6% to 7.8% +/- 1.9% by STAT5A(1*6) as compared with
      controls, but these elevated LTC-IC frequencies were strongly reduced upon re
      introduction of C/EBPalpha in STAT5A(1*6) cells, and no second cobble-stone area
      forming cells (CAFCs) could be generated from double-transduced cells.
      Enumeration of progenitors revealed that the number of colony-forming cells
      (CFCs) was reduced more than 20-fold when C/EBPalpha was co-expressed in
      STAT5A(1*6) cells. Our data indicate that down-modulation of C/EBPalpha is a
      prerequisite for STAT5-induced effects on self-renewal and myelopoiesis.

PMID- 16455948
TI  - CD44 is a phagocytic receptor.
AB  - CD44, a transmembrane adhesion molecule involved in binding and metabolism of
      hyaluronan, has additional functions in inflammatory and immune responses,
      contributing to the ingestion and clearance of particles and apoptotic cells. Our
      goal was to determine the specific role of CD44 in phagocytosis and whether it
      functions as a primary or accessory phagocytic receptor. Using hyaluronan-coated
      beads and erythrocytes coated with antiCD44 antibodies as the phagocytic prey, we
      determined that CD44 mediates efficient phagocytosis in primary murine peritoneal
      macrophages and in the murine macrophage cell line RAW 264.7. In RAW cells, the
      phagocytic index for anti-CD44-coated erythrocytes was 25 +/- 3 (mean +/- SEM)
      compared with less than 1 for erythrocytes coated with isotype-matched control
      antibodies. Uptake of anti-CD44-coated erythrocytes was abrogated by pretreatment
      with a blocking antibody to CD44 and was absent in primary cultures of CD44
      deficient murine macrophages. Down-regulation of Fc receptors by aggregated IgG
      induced internalization, which blocks uptake of IgG-coated particles, had no
      effect on CD44-mediated particle engulfment. Using a combination of
      immunoprecipitation, pharmacologic inhibition, and genetic deletion, we
      determined that CD44-mediated phagocytosis involves Syk, Rac1, and
      phosphatidylinositol 3-kinase and induced activation of the phagocyte oxidase. We
      conclude that CD44 is a competent phagocytic receptor that efficiently mediates
      internalization of large particles.

PMID- 16455949
TI  - hnRNP L regulates differences in expression of mouse integrin alpha2beta1.
AB  - There is a 2-fold variation in platelet integrin alpha2beta1 levels among inbred
      mouse strains. Decreased alpha2beta1 in 4 strains carrying Itga2 haplotype 2
      results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L)
      for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype
      1 and a 21 CA repeat sequence at this position (CA21) express twice the level of
      platelet alpha2beta1 and exhibit an equivalent gain of platelet function in
      vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to
      CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of
      hnRNP L results in decreased splicing efficiency and an increased proportion of
      alternatively spliced product. The splicing enhancer activity of CA21 in vivo is
      abolished by prior treatment with hnRNP L-specific siRNA. Thus, decreased surface
      alpha2beta1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L
      and depends on CA repeat length at a specific site in intron 1.

PMID- 16455950
TI  - Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for
      aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML.
AB  - We recently identified aberrant cytoplasmic expression of nucleophosmin (NPM) as
      the immunohistochemical marker of a large subgroup of acute myeloid leukemia
      (AML) (about one-third of adult AML) that is characterized by normal karyotype
      and mutations occurring at the exon-12 of the NPM gene. In this paper, we have
      elucidated the molecular mechanism underlying the abnormal cytoplasmic
      localization of NPM. All 29 AML-associated mutated NPM alleles so far identified
      encode abnormal proteins which have acquired at the C-terminus a nuclear export
      signal (NES) motif and lost both tryptophan residues 288 and 290 (or only the
      residue 290) which determine nucleolar localization. We show for the first time
      that both alterations are crucial for NPM mutant export from nucleus to
      cytoplasm. In fact, the cytoplasmic accumulation of NPM is blocked by leptomycin
      B and ratjadones, specific exportin-1/Crm1-inhibitors, and by reinsertion of
      tryptophan residues 288 and 290, which respectively relocate NPM mutants in the
      nucleoplasm and nucleoli. NPM leukemic mutants in turn recruit the wild-type NPM
      from nucleoli to nucleoplasm and cytoplasm. These findings indicate that
      potential therapeutic strategies aimed to retarget NPM to its physiological sites
      will have to overcome 2 obstacles, the new NES motif and the mutated
      tryptophan(s) at the NPM mutant C-terminus.

PMID- 16455951
TI  - Genetic marking of hematopoietic stem and endothelial cells: identification of
      the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1
      domain.
AB  - Using an in silico database search, we identified a novel gene encoding a cell
      surface molecule with a thrombospondin domain, and designated the gene as
      transmembrane molecule with thrombospondin module (Tmtsp). Expression profiling
      of Tmtsp using specific monoclonal antibodies and Venus, a variant of yellow
      fluorescent protein knock-in mice in the Tmtsp locus, demonstrated its specific
      expression in hematopoietic and endothelial cells. In lymphohematopoietic cells,
      Tmtsp was predominantly expressed in hematopoietic stem and progenitor cells, and
      the level of expression gradually declined as the cells differentiated. Venus
      expression faithfully traced the expression of Tmtsp, and the level of Venus
      expression correlated well to the in vitro hematopoietic activity as well as the
      in vivo bone marrow repopulating capacity. Notably, Venus expression marked the
      development of definitive hematopoiesis in both the extraembryonic yolk sac and
      the intraembryonic aorta-gonad-mesonephros (AGM) region and, in combination with
      CD41, strikingly promoted the enrichment of developing progenitors in the
      CD41(+)Venus(high) fraction at embryonic day 10.5 (E10.5). In this context, Tmtsp
      is a novel marker gene for primitive hematopoietic cells and endothelial cells,
      and Tmtsp(Venus/)(+) mice would serve as a valuable mouse model for the analysis
      of both embryonic and adult hematopoiesis, as well as for vascular biology.

PMID- 16455952
TI  - Age and acute myeloid leukemia.
AB  - We conducted a retrospective analysis of 968 adults with acute myeloid leukemia
      (AML) on 5 recent Southwest Oncology Group trials to understand how the nature of
      AML changes with age. Older study patients with AML presented with poorer
      performance status, lower white blood cell counts, and a lower percentage of
      marrow blasts. Multidrug resistance was found in 33% of AMLs in patients younger
      than age 56 compared with 57% in patients older than 75. The percentage of
      patients with favorable cytogenetics dropped from 17% in those younger than age
      56 to 4% in those older than 75. In contrast, the proportion of patients with
      unfavorable cytogenetics increased from 35% in those younger than age 56 to 51%
      in patients older than 75. Particularly striking were the increases in
      abnormalities of chromosomes 5, 7, and 17 among the elderly. The increased
      incidence of unfavorable cytogenetics contributed to their poorer outcome, and,
      within each cytogenetic risk group, treatment outcome deteriorated markedly with
      age. Finally, the combination of a poor performance status and advanced age
      identified a group of patients with a very high likelihood of dying within 30
      days of initiating induction therapy. The distinct biology and clinical responses
      seen argue for age-specific assessments when evaluating therapies for AML.

PMID- 16455953
TI  - Glycoprotein VI-dependent and -independent pathways of thrombus formation in
      vivo.
AB  - The role of the collagen receptor glycoprotein VI (GPVI) in arteriolar thrombus
      formation was studied in FcRgamma-null mice (FcRgamma(-/-)) lacking platelet
      surface GPVI. Thrombi were induced with severe or mild FeCl(3) injury. Collagen
      exposure was significantly delayed and diminished in mild compared with severe
      FeCl(3) injury. Times to initial thrombus formation and vessel occlusion were
      delayed in FcRgamma(-/-) compared with wild-type mice after severe injury.
      Platelet accumulation in wild-type mice was decreased after mild compared with
      severe injury. However, there was little difference between platelet accumulation
      after severe or mild injury in FcRgamma(-/-). These data indicate a significant
      role for GPVI in FeCl(3)-induced thrombus formation. Pretreatment of wild-type
      mice with lepirudin further impaired mild FeCl(3)-induced thrombus formation,
      demonstrating a role for thrombin. Laser-induced thrombus formation in wild-type
      and FcRgamma(-/-) was comparable. Collagen exposure to circulating blood was
      undetectable after laser injury. Normalized for thrombus size, thrombus
      associated tissue factor was 5-fold higher in laser-induced thrombi than in
      severe FeCl(3)-induced thrombi. Thus, platelet activation by thrombin appears to
      be more important after laser injury than platelet activation by GPVI-collagen.
      It may thus be important when considering targets for antithrombotic therapy to
      use multiple animal models with diverse pathways to thrombus formation.

PMID- 16455954
TI  - KLF2 provokes a gene expression pattern that establishes functional quiescent
      differentiation of the endothelium.
AB  - The flow-responsive transcription factor KLF2 is acquiring a leading role in the
      regulation of endothelial cell gene expression. A genome-wide microarray
      expression profiling is described employing lentivirus-mediated, 7-day
      overexpression of human KLF2 at levels observed under prolonged flow. KLF2 is not
      involved in lineage typing, as 42 endothelial-specific markers were unaffected.
      Rather, KLF2 generates a gene transcription profile (> 1000 genes) affecting key
      functional pathways such as cell migration, vasomotor function, inflammation, and
      hemostasis and induces a morphology change typical for shear exposure including
      stress fiber formation. Protein levels for thrombomodulin, endothelial nitric
      oxide synthase, and plasminogen activator inhibitor type-1 are altered to
      atheroprotective levels, even in the presence of the inflammatory cytokine TNF
      alpha. KLF2 attenuates cell migration by affecting multiple genes including
      VEGFR2 and the potent antimigratory SEMA3F. The distribution of Weibel-Palade
      bodies in cultured cell populations is normalized at the single-cell level
      without interfering with their regulated, RalA-dependent release. In contrast,
      thrombin-induced release of Weibel-Palade bodies is significantly attenuated,
      consistent with the proposed role of VWF release at low-shear stress regions of
      the vasculature in atherosclerosis. These results establish that KLF2 acts as a
      central transcriptional switch point between the quiescent and activated states
      of the adult endothelial cell.

PMID- 16455955
TI  - Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose
      transporter.
AB  - Leukocyte adhesion deficiency II (LAD II) is a rare congenital disease caused by
      defective fucosylation leading to immuno-deficiency and psychomotor retardation.
      We have previously identified the genetic defect of LAD II in a patient whose
      Golgi GDP-fucose transporter (GFTP) bears a single amino acid exchange that
      renders this protein nonfunctional but correctly localized to the Golgi. We now
      report a novel dual defect by which a truncated GFTP causes the disease in a new
      LAD II patient. We show that the truncation renders this GFTP unable to localize
      to the Golgi, the compartment where it is required. Furthermore, the missing part
      of the GFTP can be dissected into 2 regions, one that is needed for Golgi
      localization and one that is additionally required for the function of the GFTP.
      We investigated the subcellular localization of all known defective GFTPs
      allowing us to divide all genetically analyzed LAD II patients into 2 groups, one
      in which single amino acid exchanges in the GFTP impair its function but not its
      subcellular localization, and another group with a dual defect in function and
      Golgi expression of the GFTP due to the absence of 2 important molecular regions.

PMID- 16455957
TI  - From whence we come (happy birthday to us).

PMID- 16455956
TI  - Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with
      acute myeloid leukemia (AML).
AB  - Mutations of the nucleophosmin (NPM1) gene have recently been described in
      patients with acute myeloid leukemia (AML). To clarify the prevalence as well as
      the clinical impact of this mutation, we investigated 1485 patients with AML for
      NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408
      of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, B,
      and D) as well as 13 novel alterations in 229 analyzed cases. NPM1 mutations were
      most prevalent in patients with normal karyotype (NK) (324 of 709; 45.7%)
      compared with 58 of 686 with karyotype abnormalities (8.5%; P < .001) and were
      significantly associated with several clinical parameters (high bone marrow [BM]
      blasts, high white blood cell [WBC] and platelet counts, female sex). NPM1
      alterations were associated with FLT3-ITD mutations, even if restricted to
      patients with NK (NPM1-mut/FLT3-ITD: 43.8%; versus NPM1-wt/FLT3-ITD: 19.9%; P <
      .001). The analysis of the clinical impact in 4 groups (NPM1 and FLT3-ITD single
      mutants, double mutants, and wild-type [wt] for both) revealed that patients
      having only an NPM1 mutation had a significantly better overall and disease-free
      survival and a lower cumulative incidence of relapse. In conclusion, NPM1
      mutations represent a common genetic abnormality in adult AML. If not associated
      with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved
      response toward treatment.

PMID- 16455958
TI  - Experimental models to study development and function of the human immune system
      in vivo.
AB  - The study of development and function of the immune system in vivo has made
      intensive use of animal models, but performing such work in humans is difficult
      for experimental, practical, and ethical reasons. Confronted with this scientific
      challenge, several pioneering groups have developed in the late 1980s mouse
      models of human immune system development. Although these experimental approaches
      were proven successful and useful, they were suffering from limitations due to
      xenograft transplantation barriers. By reviewing the characteristics of the
      successive models over the last 20 years, it becomes apparent that screening of
      potentially interesting mouse strains and usage of combinations of genetic
      deficiencies has led to major advances. This is particularly true for human T
      cell development in the murine thymus. This review will focus on these advances
      and the potential future improvements that remain to be accomplished.

PMID- 16455959
TI  - Cutting edge: an alternative pathway of CD4+ T cell differentiation is induced
      following activation in the absence of gamma-chain-dependent cytokine signals.
AB  - This report addresses the role of gamma-chain cytokine signals in regulating
      CD4(+) T cell differentiation following activation. Using murine CD4(+) T cells
      lacking the Jak3 tyrosine kinase, we show that activation of these cells in the
      absence of gamma-chain-dependent cytokine signals induces an alternative pathway
      of T cell differentiation. Specifically, activated Jak3(-/-) CD4(+) T cells
      produce IL-10, TGF-beta, and IFN-gamma, but not IL-2 or IL-4, and are unable to
      proliferate in vitro. In addition, Jak3(-/-) CD4(+) T cells express high levels
      of programmed death-1 and lymphocyte activation gene-3 and modestly suppress the
      proliferation of wild-type CD4(+) T cells in coculture assays. Together, these
      features demonstrate a striking similarity between Jak3(-/-) CD4(+) T cells and
      the regulatory T cells that have been shown to suppress immune responses in vitro
      and in vivo. We conclude that Jak3 is a critical component of signaling pathways
      that regulate T cell differentiation into effector vs regulatory lineages.

PMID- 16455960
TI  - Cutting edge: influence of the TCR Vbeta domain on the selection of semi
      invariant NKT cells by endogenous ligands.
AB  - Invariant Valpha14 (Valpha14i) NKT cells are a murine CD1d-dependent regulatory T
      cell subset characterized by a Valpha14-Jalpha18 rearrangement and expression of
      mostly Vbeta8.2 and Vbeta7. Whereas the TCR Vbeta domain influences the binding
      avidity of the Valpha14i TCR for CD1d-alpha-galactosylceramide complexes, with
      Vbeta8.2 conferring higher avidity binding than Vbeta7, a possible impact of the
      TCR Vbeta domain on Valpha14i NKT cell selection by endogenous ligands has not
      been studied. In this study, we show that thymic selection of Vbeta7(+), but not
      Vbeta8.2(+), Valpha14i NKT cells is favored in situations where endogenous ligand
      concentration or TCRalpha-chain avidity are suboptimal. Furthermore, thymic
      Vbeta7(+) Valpha14i NKT cells were preferentially selected in vitro in response
      to CD1d-dependent presentation of endogenous ligands or exogenously added self
      ligand isoglobotrihexosylceramide. Collectively, our data demonstrate that the
      TCR Vbeta domain influences the selection of Valpha14i NKT cells by endogenous
      ligands, presumably because Vbeta7 confers higher avidity binding.

PMID- 16455961
TI  - Cutting edge: novel human dendritic cell- and monocyte-attracting chemokine-like
      protein identified by fold recognition methods.
AB  - Chemokines play an important role in the immune system by regulating cell
      trafficking in homeostasis and inflammation. In this study, we report the
      identification and characterization of a novel cytokine-like protein, DMC
      (dendritic cell and monocyte chemokine-like protein), which attracts dendritic
      cells and monocytes. The key to the identification of this putative new chemokine
      was the application of threading techniques to its uncharacterized sequence.
      Based on our studies, DMC is predicted to have an IL-8-like chemokine fold and to
      be structurally and functionally related to CXCL8 and CXCL14. Consistent with our
      predictions, DMC induces migration of monocytes and immature dendritic cells.
      Expression studies show that DMC is constitutively expressed in lung, suggesting
      a potential role for DMC in recruiting monocytes and dendritic cells from blood
      into lung parenchyma.

PMID- 16455962
TI  - Cutting edge: enhancement of antibody responses through direct stimulation of B
      and T cells by type I IFN.
AB  - Type I IFN (IFN-alphabeta) is induced rapidly by infection and plays a key role
      in innate antiviral defense. IFN-alphabeta also exerts stimulatory effects on the
      adaptive immune system and has been shown to enhance Ab and T cell responses. We
      have investigated the importance of B and T cells as direct targets of IFN
      alphabeta during IFN-alpha-mediated augmentation of the Ab response against a
      soluble protein Ag. Strikingly, the ability of IFN-alpha to stimulate the Ab
      response and induce isotype switching was markedly reduced in mice in which B
      cells were selectively deficient for the IFN-alphabetaR. Moreover, IFN-alpha
      mediated enhancement of the Ab response was also greatly impaired in mice in
      which T cells were selectively IFN-alphabetaR-deficient. These results indicate
      that IFN-alphabetaR signaling in both B and T cells plays an important role in
      the stimulation of Ab responses by IFN-alphabeta.

PMID- 16455963
TI  - Cutting edge: gut microenvironment promotes differentiation of a unique memory
      CD8 T cell population.
AB  - Whether tissue microenvironment influences memory CD8 T cell differentiation is
      unclear. We demonstrate that virus-specific intraepithelial lymphocytes in gut
      resemble neither central nor effector memory CD8 T cells isolated from spleen or
      blood. This unique phenotype arises in situ within the gut, suggesting that
      anatomic location plays an inductive role in the memory differentiation program.
      In support of this hypothesis, memory CD8 T cells changed phenotype upon change
      in location. After transfer and in vivo restimulation, gut or spleen memory cells
      proliferated, disseminated into spleen and gut, and adopted the memory T cell
      phenotype characteristic of their new environment. Our data suggests that
      anatomic location directly impacts the memory T cell differentiation program.

PMID- 16455964
TI  - CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic
      stress.
AB  - T cell dysfunction that occurs after surgery or trauma is associated with a poor
      clinical outcome. We describe that myeloid suppressor cells expressing
      CD11b(+)/Gr-1(+) markers invade the spleen after traumatic stress and suppress T
      cell function through the production of arginase 1. We created a consistent model
      of traumatic stress in C57BL/6 mice to perform this work. A significant number of
      CD11b(+)/Gr-1(+) cells expressing arginase 1 accumulated in T cell zones around
      the germinal centers of the white pulp of the spleen within 6 h of trauma and
      lasted for at least 72 h. Increased arginase activity and arginase 1 expression,
      along with increased [(3)H]arginine uptake, l-arginine depletion, and l-ornithine
      accumulation in the culture medium, were observed exclusively in CD11b(+)/Gr-1(+)
      cells after traumatic stress. Flow cytometry revealed CD11b(+)/Gr-1(+) as a
      heterogeneous myeloid suppressor cell also expressing low levels of MHC class I
      and II, CD80, CD86, CD31, and others. When compared with controls, trauma-induced
      CD11b(+)/Gr-1(+) cells significantly inhibited CD3/CD28-mediated T cell
      proliferation, TCR zeta-chain expression, and IL-2 production. The suppressive
      effects by trauma CD11b(+)/Gr-1(+) cells were overcome with the arginase
      antagonist N-hydroxy-nor-l-arginine or extrasupplementation of medium with l
      arginine. Poor Ag-presenting capacity of control and trauma-induced CD11b(+)/Gr
      1(+) cells was detected in allogeneic murine leukocyte reaction. This study
      demonstrates that CD11b(+)/Gr-1(+) cells invade the spleen following traumatic
      stress and cause T cell dysfunction by an arginase-mediated mechanism, probably
      that of arginine depletion. Understanding the mechanism of immune suppression by
      these cells has important clinical implications in the treatment of immune
      dysfunction after trauma or surgery.

PMID- 16455965
TI  - Accelerated macrophage apoptosis induces autoantibody formation and organ damage
      in systemic lupus erythematosus.
AB  - Increased monocyte/macrophage (Mphi) apoptosis occurs in patients with systemic
      lupus erythematosus (SLE) and is mediated, at least in part, by an autoreactive
      CD4(+) T cell subset. Furthermore, autoreactive murine CD4(+) T cells that kill
      syngeneic Mphi in vitro induce a lupus-like disease in vivo. However, it is
      unclear whether increased Mphi apoptosis in SLE per se is sufficient to
      accelerate/promote autoimmunity. We have investigated whether increased Mphi
      apoptosis in vivo, induced by the administration of clodronate liposomes, can
      exacerbate the autoimmune phenotype in NZB x SWR (SNF(1)) lupus-prone mice, and
      induce autoantibody production in haplotype-matched BALB/c x DBA1 (DBF(1)) non
      lupus-prone mice. Lupus-prone mice SNF(1) mice that were treated with clodronate
      liposomes, but not mice treated with vehicle, developed significant increases in
      autoantibodies to dsDNA, nucleosomes, and the idiotypically related family of
      nephritic Abs Id(LN)F(1), when compared with untreated SNF(1) mice. Furthermore,
      clodronate treatment hastened the onset of proteinuria and worsened SNF(1) lupus
      nephritis. When compared with vehicle-treated controls, clodronate-treated non
      lupus-prone DBF(1) mice developed significantly higher levels of anti-nucleosome
      and Id(LN)F(1) Abs but did not develop lupus nephritis. We propose that Mphi
      apoptosis contributes to the pathogenesis of autoantibody formation and organ
      damage through both an increase in the apoptotic load and impairment in the
      clearance of apoptotic material. This study suggests that mechanisms that induce
      scavenger cell apoptosis, such as death induced by autoreactive cytotoxic T cells
      observed in SLE, could play a pathogenic role and contribute to the severity of
      the disease.

PMID- 16455966
TI  - LFA-1-dependent HuR nuclear export and cytokine mRNA stabilization in T cell
      activation.
AB  - Lymphokine gene expression is a precisely regulated process in T cell-mediated
      immune responses. In this study we demonstrate that engagement of the beta(2)
      integrin LFA-1 in human peripheral T cells markedly extends the half-life of TNF
      alpha, GM-CSF, and IL-3 mRNA, as well as a chimeric beta-globin mRNA reporter
      construct containing a strongly destabilizing class II AU-rich element from the
      GM-CSF mRNA 3'-untranslated region. This integrin-enhanced mRNA stability leads
      to augmented protein production, as determined by TNF-alpha ELISPOT assays.
      Furthermore, T cell stimulation by LFA-1 promotes rapid nuclear-to-cytoplasmic
      translocation of the mRNA-stabilizing protein HuR, which in turn is capable of
      binding an AU-rich element sequence in vitro. Abrogation of HuR function by use
      of inhibitory peptides, or marked reduction of HuR levels by RNA interference,
      prevents LFA-1 engagement-mediated stabilization of T cell TNF-alpha or IFN-gamma
      transcripts, respectively. Thus, HuR-mediated mRNA stabilization, stimulated by
      integrin engagement and controlled at the level of HuR nuclear export, is
      critically involved in T cell activation.

PMID- 16455967
TI  - IL-3-mediated TNF production is necessary for mast cell development.
AB  - Mouse mast cell development and survival are largely controlled by the cytokines
      IL-3 and stem cell factor (SCF). We have found that IL-3 stimulation of bone
      marrow cells induces the production of TNF via a PI3K- and MAPK kinase/ERK
      dependent pathway. Specifically, Mac-1-positive cells were responsible for TNF
      production, which peaked on days 7-10 of culture and decreased rapidly
      thereafter. The importance of IL-3-induced TNF secretion was demonstrated by the
      failure of TNF-deficient bone marrow cells to survive for >3 wk when cultured in
      IL-3 and SCF, a defect that was reversed by the addition of soluble TNF. The
      development of human mast cells from bone marrow progenitors was similarly
      hampered by the addition of TNF-blocking Abs. Cell death was due to apoptosis,
      which occurred with changes in mitochondrial membrane potential and caspase
      activation. Apoptosis appeared to be due to loss of IL-3 signaling, because TNF
      deficient cells were less responsive than their wild-type counterparts to IL-3
      mediated survival. In vitro cultured mast cells from TNF-deficient mice also
      demonstrated reduced expression of the high affinity IgE receptor, which was
      restored to normal levels by the addition of soluble TNF. Finally, TNF-deficient
      mice demonstrated a 50% reduction in peritoneal mast cell numbers, indicating
      that TNF is an important mast cell survival factor both in vitro and in vivo.

PMID- 16455968
TI  - Role of MHC class II on memory B cells in post-germinal center B cell homeostasis
      and memory response.
AB  - We investigated the role of B cell Ag presentation in homeostasis of the memory B
      cell compartment in a mouse model where a conditional allele for the beta-chain
      of MHC class II (MHC-II) is deleted in the vast majority of all B cells by cd19
      promoter-mediated expression of Cre recombinase (IA-B mice). Upon T cell
      dependent immunization, a small number of MHC-II(+) B cells in IA-B mice
      dramatically expanded and restored normal albeit delayed levels of germinal
      center (GC) B cells with an affinity-enhancing somatic mutation to Ag. IA-B mice
      also established normal levels of MHC-II(+) memory B cells, which, however,
      subsequently lost MHC-II expression by ongoing deletion of the conditional iab
      allele without significant loss in their number. Furthermore, in vivo Ag
      restimulation of MHC-II(-) memory B cells of IA-B mice failed to cause
      differentiation into plasma cells (PCs), even in the presence of Ag-specific
      CD4(+) T cells. In addition, both numbers and Ag-specific affinity of long-lived
      PCs during the late post-GC phase, as well as post-GC serum affinity maturation,
      were significantly reduced in IA-B mice. These results support a notion that MHC
      II-dependent T cell help during post-GC phase is not absolutely required for the
      maintenance of memory B cell frequency but is important for their differentiation
      into PCs and for the establishment of the long-lived PC compartment.

PMID- 16455969
TI  - Hyperthermia enhances CTL cross-priming.
AB  - Dendritic cells (DCs) loaded with killed allogeneic melanoma cells can cross
      prime naive CD8(+) T cells to differentiate into melanoma-specific CTLs in 3-wk
      cultures. In this study we show that DCs loaded with killed melanoma cells that
      were heated to 42 degrees C before killing are more efficient in cross-priming of
      naive CD8(+) T cells than DCs loaded with unheated killed melanoma cells. The
      enhanced cross-priming was demonstrated by several parameters: 1) induction of
      naive CD8(+) T cell differentiation in 2-wk cultures, 2) enhanced killing of
      melanoma peptide-pulsed T2 cells, 3) enhanced killing of HLA-A*0201(+) melanoma
      cells in a standard 4-h chromium release assay, and 4) enhanced capacity to
      prevent tumor growth in vitro in a tumor regression assay. Two mechanisms might
      explain the hyperthermia-induced enhanced cross-priming. First, heat-treated
      melanoma cells expressed increased levels of 70-kDa heat shock protein (HSP70),
      and enhanced cross-priming could be reproduced by overexpression of HSP70 in
      melanoma cells transduced with HSP70 encoding lentiviral vector. Second,
      hyperthermia resulted in the increased transcription of several tumor Ag
      associated Ags, including MAGE-B3, -B4, -A8, and -A10. Thus, heat treatment of
      tumor cells permits enhanced cross-priming, possibly via up-regulation of both
      HSPs and tumor Ag expression.

PMID- 16455970
TI  - B cell tolerance checkpoints that restrict pathways of antigen-driven
      differentiation.
AB  - Autoreactive B cells can be regulated by deletion, receptor editing, or anergy.
      Rheumatoid factor (RF)-expressing B lymphocytes in normal mice are not controlled
      by these mechanisms, but they do not secrete autoantibody and were presumed to
      ignore self-Ag. Surprisingly, we now find that these B cells are not quiescent,
      but instead are constitutively and specifically activated by self-Ag. In BALB/c
      mice, RF B cells form germinal centers (GCs) but few Ab-forming cells (AFCs). In
      contrast, autoimmune mice that express the autoantigen readily generate RF AFCs.
      Most interestingly, autoantigen-specific RF GCs in BALB/c mice appear defective.
      B cells in such GCs neither expand nor are selected as efficiently as equivalent
      cells in autoimmune mice. Thus, our data establish two novel checkpoints of
      autoreactive B cell regulation that are engaged only after initial autoreactive B
      cell activation: one that allows GCs but prevents AFC formation and one that
      impairs selection in the GC. Both of these checkpoints fail in autoimmunity.

PMID- 16455971
TI  - P2X7 receptors regulate NKT cells in autoimmune hepatitis.
AB  - Adenine nucleotides induce danger signals in T cells via purinergic receptors,
      raising the question whether they exert similar effects on innate immunity. Here
      we show that micromolar concentrations of nicotinamide adenine dinucleotide (NAD)
      induce a rapid increase of annexin V staining in NKT cells in vitro, a response
      that requires expression of P2X(7)Rs. Consistent with this result, treatment of
      mice with NAD causes a temporary decrease of NKT cells in the liver and protects
      from Con A- and alpha-galactosylceramide-induced hepatitis, both of which require
      functional NKT cells. Resistance to liver injury is associated with decreased
      cytokine production by NKT cells in NAD-treated mice. In contrast, when NAD is
      injected into Con A- or alpha-galactosylceramide-primed mice, liver injury is
      exacerbated and cytokine production by NKT cells is increased. This effect is
      caused by P2X(7)R-mediated stimulation of activated NKT cells. In agreement, mice
      lacking P2X(7)Rs on lymphocytes suffer reduced liver injury, and animals lacking
      ADP-ribosyltransferase, the enzyme that uses NAD to attach ADP-ribosyl groups to
      cell surfaces, are also resistant to Con A-induced hepatitis. These results
      prompt the conclusion that engagement of P2X(7)Rs on NKT cells inhibits naive,
      while stimulating activated cells, resulting in suppression or stimulation of
      autoimmune hepatitis.

PMID- 16455973
TI  - Distinct mechanisms control human naive and antigen-experienced CD8+ T lymphocyte
      proliferation.
AB  - Human Ag-specific CD8(+) T lymphocytes are heterogeneous and include functionally
      distinct populations. In this study, we report that at least two distinct
      mechanisms control the expansion of circulating naive, memory, and effector
      CD8(+) T lymphocytes when exposed to mitogen or Ag stimulation. The first one
      leads to apoptosis and occurs shortly after in vitro stimulation. Susceptibility
      to cell death is prominent among primed T cell subsets, and it is inversely
      correlated with the size of the ex vivo Bcl-2(high) population within these
      subsets. Importantly, the Bcl-2(high) phenotype is associated to the proportion
      of responsive CD8(+) T cells, independently of their differentiation stage. The
      second one depends on the expression of newly synthesized cyclin-dependent kinase
      inhibitor p16(INK4a) that occurs in a significant fraction of T cells that had
      been actively cycling, leading to their cell cycle arrest upon stimulation.
      Strikingly, accumulation of p16(INK4a) protein preferentially occurs in naive as
      opposed to primed derived T lymphocytes and is not related to apoptosis.
      Significant levels of p16 are readily detectable in a small number of ex vivo
      CD8(+) T cells. Our observations reveal that activation-induced p16 expression
      represents an alternative process to apoptosis, limiting the proliferation
      potential of activated naive derived T lymphocytes.

PMID- 16455972
TI  - A major lung CD103 (alphaE)-beta7 integrin-positive epithelial dendritic cell
      population expressing Langerin and tight junction proteins.
AB  - Dendritic cells (DC) mediate airway Ag presentation and play key roles in asthma
      and infections. Although DC subsets are known to perform different functions,
      their occurrence in mouse lungs has not been clearly defined. In this study,
      three major lung DC populations have been found. Two of them are the myeloid and
      plasmacytoid DC (PDC) well-characterized in other lymphoid organs. The third and
      largest DC population is the integrin alpha(E) (CD103) beta(7)-positive and I
      A(high)CD11c(high)-DC population. This population was found to reside in the lung
      mucosa and the vascular wall, express a wide variety of adhesion and
      costimulation molecules, endocytose avidly, present Ag efficiently, and produce
      IL-12. Integrin alpha(E)beta(7)(+) DC (alphaE-DC) were distinct from
      intraepithelial lymphocytes and distinguishable from CD11b(high) myeloid and
      mPDCA-1(+)B220(+)Gr-1(+) PDC populations in surface marker phenotype, cellular
      functions, and tissue localization. Importantly, this epithelial DC population
      expressed high levels of the Langerhans cell marker Langerin and the tight
      junction proteins Claudin-1, Claudin-7, and ZO-2. In mice with induced airway
      hyperresponsiveness and eosinophilia, alphaE-DC numbers were increased in lungs,
      and their costimulation and adhesion molecules were up-regulated. These studies
      show that alphaE-DC is a major and distinct lung DC population and a prime
      candidate APC with the requisite surface proteins for migrating across the airway
      epithelia for Ag and pathogen capture, transport, and presentation. They exhibit
      an activated phenotype in allergen-induced lung inflammation and may play
      significant roles in asthma pathogenesis.

PMID- 16455974
TI  - NF-kappaB-dependent regulation of the timing of activation-induced cell death of
      T lymphocytes.
AB  - One of the mechanisms by which activated T cells die is activation-induced cell
      death (AICD). This pathway requires persistent stimulation via the TCR and
      engagement of death receptors. We found that TCR stimulation led to transient
      nuclear accumulation of the NF-kappaB component p65/RelA. In contrast, nuclear c
      Rel levels remained high even after extended periods of activation. Loss of
      nuclear p65/RelA correlated with the onset of AICD, suggesting that p65/RelA
      target genes may maintain cell viability. Quantitative RNA analyses showed that
      three of several putative NF-kappaB-dependent antiapoptotic genes were expressed
      with kinetics that paralleled nuclear expression of p65/RelA. Of these three,
      ectopic expression only of Gadd45beta protected significantly against AICD,
      whereas IEX-1 and Bcl-x(L) were much less effective. We propose that the timing
      of AICD, and thus the length of the effector phase, are regulated by transient
      expression of a subset of p65/RelA-dependent antiapoptotic genes.

PMID- 16455975
TI  - CD8 T cells specific for a donor-derived, self-restricted transplant antigen are
      nonpathogenic bystanders after vascularized heart transplantation in mice.
AB  - CD8 T cell cross-priming, an established mechanism of protective antiviral
      immunity, was originally discovered during studies involving minor
      transplantation Ags. It is unclear whether or how cross-primed CD8 T cells,
      reactive to donor-derived, but recipient class I MHC-restricted epitopes, could
      injure a fully MHC-disparate, vascularized transplant. To address this question
      we studied host class I MHC-restricted, male transplantation Ag-reactive T cell
      responses in female recipients of fully MHC-disparate, male heart transplants.
      Cross-priming to the immune-dominant determinant HYUtyp occurred at low frequency
      after heart transplantation. CD8 T cell preactivation through immunization with
      HYUtyp mixed in CFA did not alter the kinetics of acute rejection. Furthermore,
      neither HYUtyp immunization nor adoptive transfer of HYUtyp-specific TCR
      transgenic T cells affected outcome in 1) a model of chronic rejection in the
      absence of immunosuppression or 2) a model of allograft acceptance induced by
      costimulatory blockade. The results support the contention that CD8 T cells
      reactive to host-restricted, but donor-derived, Ags are highly specific and are
      nonpathogenic bystanders during rejection of MHC-disparate cardiac allografts.

PMID- 16455976
TI  - Expression and regulation of the orphan receptor RDC1 and its putative ligand in
      human dendritic and B cells.
AB  - Based on phylogenetic analysis and chromosomal mapping, the orphan receptor RDC1
      was proposed to be a chemokine receptor. In this study we examined the expression
      of RDC1 on leukocytes by measuring mRNA levels and receptor expression using a
      new specific mAb. Both mRNA and protein levels were high in monocytes and B
      cells, relatively low on immature dendritic cells (DC), and up-regulated during
      final stages of maturation. Strikingly, in mature plasmacytoid DC the mRNA was up
      regulated, but did not correlate with protein surface expression. We indeed
      report that CpG-activated plasmacytoid DC produce a putative ligand for RDC1,
      which selectively down-regulates RDC1, but not CXCR4 on primary human B cells.
      RDC1 expression was found to be tightly regulated during B cell development and
      differentiation. In blood-derived switch memory B cells, the expression of RDC1
      appeared to correlate with the ability to differentiate into plasma cells upon
      activation, suggesting that RDC1 is a marker for memory B cells, which are
      competent to become Ab-secreting cells.

PMID- 16455977
TI  - Differential role for cyclic AMP response element binding protein-1 in multiple
      stages of B cell development, differentiation, and survival.
AB  - CREB-1 is expressed in the bone marrow and in developing B cells. To determine
      the role of CREB-1 in developing B cells in the bone marrow, several lines of
      transgenic (Tg) mice overexpressing a dominant-negative Ser(119-ala)
      phosphomutant CREB-1 in the bone marrow were generated. Analysis of RNA and
      protein revealed expression of the transgene in the bone marrow. Flow cytometric
      analysis of bone marrow cells from Tg mice revealed approximately 70% increase in
      pre-B1 (CD43(+)B220(+)CD24(+(int))) and approximately 60% decreased pre-BII
      (CD43(+)B220(+)CD24(++(high))) cells, indicating a developmental block in pre-BI
      to pre-BII transition. Consistent with this, the Tg mice showed approximately 4
      fold decrease in immature and mature B cells in the bone marrow. RT-PCR analysis
      of RNA from Tg mice revealed increased JunB and c-Jun in pre-BII cells associated
      with decreased S-phase entry. Adoptive transfer of bone marrow cells into RAG-2(
      /-) mice resulted in reconstitution of non-Tg but not Tg bone marrow-derived
      CD43(+)B220(+)CD24(high) population that is normally absent in RAG-2(-/-) mice.
      In the periphery, the Tg mice exhibited decreased CD21(dim)CD23(high)IgM(+)
      follicular B cells in the spleen and increased B1a and B1b B cells in the
      peritoneum. While exhibiting normal Ab responses to T-independent Ags and primary
      response to the T-dependent Ag DNP-keyhole limpet hemocyanin, the Tg mice
      exhibited severely impaired secondary Ab responses. These studies provide the
      first evidence for a differential role for CRE-binding proteins in multiple
      stages of B cell development, functional maturation, and B1 and B2 B cells.

PMID- 16455978
TI  - The JNK are important for development and survival of macrophages.
AB  - We report in this study that activation of the JNK by the growth factor, CSF-1 is
      critical for macrophage development, proliferation, and survival. Inhibition of
      JNK with two distinct classes of inhibitors, the pharmacological agent SP600125,
      or the peptide D-JNKI1 resulted in cell cycle inhibition with an arrest at the
      G(2)/M transition and subsequent apoptosis. JNK inhibition resulted in decreased
      expression of CSF-1R (c-fms) and Bcl-x(L) mRNA in mature macrophages and
      repressed CSF-1-dependent differentiation of bone marrow cells to macrophages.
      Macrophage sensitivity to JNK inhibitors may be linked to phosphorylation of the
      PU.1 transcription factor. Inhibition of JNK disrupted PU.1 binding to an element
      in the c-fms gene promoter and decreased promoter activity. Promoter activity
      could be restored by overexpression of PU.1. A comparison of expression profiles
      of macrophages with 22 other tissue types showed that genes that signal JNK
      activation downstream of tyrosine kinase receptors, such as focal adhesion
      kinase, Nck-interacting kinase, and Rac1 and scaffold proteins are highly
      expressed in macrophages relative to other tissues. This pattern of expression
      may underlie the novel role of JNK in macrophages.

PMID- 16455979
TI  - Developmental alterations in thymocyte sensitivity are actively regulated by MHC
      class II expression in the thymic medulla.
AB  - Developing thymocytes are positively selected if they respond to self-MHC-peptide
      complexes, yet mature T cells are not activated by those same self-complexes. To
      avoid autoimmunity, positive selection must be followed by a period of maturation
      when the cellular response to TCR signals is altered. The mechanisms that mediate
      this postselection developmental tuning remain largely unknown. Specifically, it
      is unknown whether developmental tuning is a preprogrammed outcome of positive
      selection or if it is sensitive to ongoing interactions between the thymocyte and
      the thymic stroma. We probed the requirement for MHC class II-TCR interactions in
      postselection maturation by studying single positive (SP) CD4 thymocytes from
      K14/A(beta)(b) mice, in which CD4 T cells cannot interact with MHC class II in
      the thymic medulla. We report here that SP CD4 thymocytes must receive MHC class
      II signals to avoid hyperactive responses to TCR signals. This hyperactivity
      correlates with decreased expression of CD5; however, developmental tuning can
      occur independently of CD5, correlating instead with differences in the
      distribution of Lck. Thus, the maturation of postselection SP CD4 thymocytes is
      an active process mediated by ongoing interactions between the T cell and MHC
      class II molecules. This represents a novel mechanism by which the thymic medulla
      prevents autoreactivity.

PMID- 16455980
TI  - Mast cells enhance T cell activation: importance of mast cell costimulatory
      molecules and secreted TNF.
AB  - We recently reported that mast cells stimulated via FcepsilonRI aggregation can
      enhance T cell activation by a TNF-dependent mechanism. However, the molecular
      mechanisms responsible for such IgE-, Ag- (Ag-), and mast cell-dependent
      enhancement of T cell activation remain unknown. In this study we showed that
      mouse bone marrow-derived cultured mast cells express various costimulatory
      molecules, including members of the B7 family (ICOS ligand (ICOSL), PD-L1, and PD
      L2) and the TNF/TNFR families (OX40 ligand (OX40L), CD153, Fas, 4-1BB, and
      glucocorticoid-induced TNFR). ICOSL, PD-L1, PD-L2, and OX40L also are expressed
      on APCs such as dendritic cells and can modulate T cell function. We found that
      IgE- and Ag-dependent mast cell enhancement of T cell activation required
      secreted TNF; that TNF can increase the surface expression of OX40, ICOS, PD-1,
      and other costimulatory molecules on CD3(+) T cells; and that a neutralizing Ab
      to OX40L, but not neutralizing Abs to ICOSL or PD-L1, significantly reduced
      IgE/Ag-dependent mast cell-mediated enhancement of T cell activation. These
      results indicate that the secretion of soluble TNF and direct cell-cell
      interactions between mast cell OX40L and T cell OX40 contribute to the ability of
      IgE- and Ag-stimulated mouse mast cells to enhance T cell activation.

PMID- 16455981
TI  - Re-evaluating the generation of a "proteasome-independent" MHC class I-restricted
      CD8 T cell epitope.
AB  - The proteasome is primarily responsible for the generation of MHC class I
      restricted CTL epitopes. However, some epitopes, such as NP(147-155) of the
      influenza nucleoprotein (NP), are presented efficiently in the presence of
      proteasome inhibitors. The pathways used to generate such apparently "proteasome
      independent" epitopes remain poorly defined. We have examined the generation of
      NP(147-155) and a second proteasome-dependent NP epitope, NP(50-57), using cells
      adapted to growth in the presence of proteasome inhibitors and also through
      protease overexpression. We observed that: 1) Ag processing and presentation
      proceeds in proteasome-inhibitor adapted cells but may become more dependent, at
      least in part, on nonproteasomal protease(s), 2) tripeptidyl peptidase II does
      not substitute for the proteasome in the generation of NP(147-155), 3)
      overexpression of leucine aminopeptidase, thymet oligopeptidase, puromycin
      sensitive aminopeptidase, and bleomycin hydrolase, has little impact on the
      processing and presentation of NP(50-57) or NP(147-155), and 4) proteasome
      inhibitor treatment altered the specificity of substrate cleavage by the
      proteasome using cell-free digests favoring NP(147-155) epitope preservation.
      Based on these results, we propose a central role for the proteasome in epitope
      generation even in the presence of proteasome inhibitors, although such
      inhibitors will likely alter cleavage patterns and may increase the dependence of
      the processing pathway on postproteasomal enzymes.

PMID- 16455982
TI  - Temporal and dose-dependent relationships between in vivo B cell receptor
      targeted proliferation and deletion-induced by a microbial B cell toxin.
AB  - The effective functioning of the adaptive immune system requires careful clonal
      regulation within the B cell compartment. Some microbial pathogens produce
      virulence factors, like staphylococcal protein A, which interact at high
      frequencies with B lymphocyte through unconventional binding sites in BCR
      variable region frameworks conserved during evolution. We have characterized the
      in vivo effect of staphylococcal protein A treatment on peripheral B cells
      bearing susceptible BCR, and found a dose-dependent direct relationship over the
      range of 2 mg to <0.2 microg in the magnitude of induced BCR-targeted supraclonal
      cell death. Significantly, some level of targeted B cell proliferation was always
      detectable, with greatest interim supraclonal expansion demonstrated at 2 days
      after 20-microg treatment. Subsequently, this transient expansion always
      collapsed. In direct comparisons, i.p. treatment was more efficacious than i.v.
      treatment, although at higher doses this finding was less marked. These studies
      elucidate a general paradigm in which in vivo encounters with a B cell
      superantigen are uniformly associated with proliferative expansion followed by
      deletion that is more rapid and complete with higher doses, whereas lower doses
      lead to greater transient in vivo expansion with delayed deletion to levels at
      later times that are still quantitatively proportional to the dose. Our results
      document the potent in vivo B cell-targeted properties of a microbial B cell
      superantigen, even at submicrogram doses associated with great molar excess of
      circulating Ig, and clearly illustrate the intertwined relationships between
      targeted proliferative cycling and apoptotic death that is induced by a microbial
      B cell superantigen.

PMID- 16455983
TI  - Human mast cells undergo TRAIL-induced apoptosis.
AB  - Mast cells (MC), supposedly long-lived cells, play a key role in allergy and are
      important contributors to other inflammatory conditions in which they undergo
      hyperplasia. In humans, stem cell factor (SCF) is the main regulator of MC
      growth, differentiation, and survival. Although human MC numbers may also be
      regulated by apoptotic cell death, there have been no reports concerning the role
      of the extrinsic apoptotic pathway mediated by death receptors in these cells. We
      examined expression and function of death receptors for Fas ligand and TRAIL in
      human MC. Although the MC leukemia cell line HMC-1 and human lung-derived MC
      expressed both Fas and TRAIL-R, MC lines derived from cord blood (CBMC) expressed
      only TRAIL-R. Activation of TRAIL-R resulted in caspase 3-dependent apoptosis of
      CBMC and HMC-1. IgE-dependent activation of CBMC increased their susceptibility
      to TRAIL-mediated apoptosis. Results suggest that TRAIL-mediated apoptosis may be
      a mechanism of regulating MC survival in vivo and, potentially, for down
      regulating MC hyperplasia in pathologic conditions.

PMID- 16455984
TI  - Adaptive tolerance and clonal anergy are distinct biochemical states.
AB  - Adaptive tolerance is a process by which T cells become desensitized when Ag
      stimulation persists following an initial immune response in vivo. To examine the
      biochemical changes in TCR signaling present in this state, we used a mouse model
      in which Rag2(-/-) TCR-transgenic CD4(+) T cells were transferred into
      CD3epsilon(-/-) recipients expressing their cognate Ag. Compared with naive T
      cells, adaptively tolerant T cells had normal levels of TCR and slightly
      increased levels of CD4. Following activation with anti-TCR and anti-CD4 mAbs,
      the predominant signaling block in the tolerant cells was at the level of Zap70
      kinase activity, which was decreased 75% in vitro. Phosphorylations of the Zap70
      substrates (linker of activated T cells and phospholipase Cgamma1 were also
      profoundly diminished. This proximal defect impacted mostly on the calcium/NFAT
      and NF-kappaB pathways, with only a modest decrease in ERK1/2 phosphorylation.
      This state was contrasted with T cell clonal anergy in which the RAS/MAPK pathway
      was preferentially impaired and there was much less inhibition of Zap70 kinase
      activity. Both hyporesponsive states manifested a block in IkappaB degradation.
      These results demonstrate that T cell adaptive tolerance and clonal anergy are
      distinct biochemical states, possibly providing T cells with two molecular
      mechanisms to curtail responsiveness in different biological circumstances.

PMID- 16455985
TI  - Antigen exposure during enhanced CTLA-4 expression promotes allograft tolerance
      in vivo.
AB  - The role of CTLA-4 in tolerance is primarily inferred from knockout and blocking
      studies. Anti-CD45RB mediates allograft tolerance in mice by inducing CTLA-4
      expression on CD4 cells, providing a novel opportunity to determine how
      therapeutic enhancement of CTLA-4 promotes tolerance. We now show that induced
      CTLA-4 expression normally resolves by day 17. Although thymectomy prolongs
      enhanced CTLA-4 expression, long-term engraftment is unaffected. To address the
      temporal relationship between increased CTLA-4 expression and engraftment,
      transplantation was delayed for various times after anti-CD45RB treatment.
      Delaying transplantation for 7 days (when CTLA-4 expression had peaked but
      treatment mAb was no longer detectable), resulted in long-term engraftment
      comparable to transplantation with no delay (day 0). Delaying transplantation
      from 10 to 18 days led to a progressively poorer outcome as CTLA-4 expression
      returned to baseline. This suggested that Ag exposure while CTLA-4 expression is
      enhanced is sufficient to induce long-term engraftment. To substantiate this, on
      day 0, anti-CD45RB-treated mice received BALB/c vs unrelated alloantigen,
      followed by transplantation of BALB/c islets 10 days later. Whereas recipients
      exposed to unrelated Ag experienced acute rejection, recipients exposed to donor
      Ag achieved long-term engraftment. Anti-CD45RB-treated mice exposed to
      alloantigen exhibited anergic CD4(+)CD25(-) effector cells and regulatory
      CD4(+)CD25(+) cells. Moreover, CD25 depletion in the peritransplant period
      prevented anti-CD45RB-mediated engraftment. Thus, exposure of CD4 cells
      expressing CTLA-4 to donor Ag is necessary and sufficient to induce long-term
      engraftment which appears to be mediated by both regulation and anergy.

PMID- 16455986
TI  - Thymocyte negative selection is mediated by protein kinase C- and Ca2+-dependent
      transcriptional induction of bim [corrected].
AB  - The processes of positive and negative selection in the thymus both determine the
      population of T cells that will enter the peripheral immune system and eliminate
      self-reactive T cells by apoptosis. Substantial evidence indicates that TCR
      signal intensity mediates this cell fate choice: low-intensity signals lead to
      survival and differentiation, whereas high-intensity signals generated by self-Ag
      lead to cell death. The molecular mechanism by which these graded signals are
      converted to discrete outcomes is not understood. Positive selection requires the
      Ca(2+)-dependent phosphatase calcineurin, whereas negative selection requires the
      proapoptotic Bcl-2 family member Bcl-2-interacting mediator of cell death (Bim).
      In this study, we investigated the regulation of Bim expression and the role of
      Ca(2+) in mediating negative selection. Our results show that transcription is
      necessary for both negative selection and Bim induction. Surprisingly, we also
      found that Ca(2+) is necessary for Bim induction. Induction of bim transcription
      appears to involve protein kinase C, but not calcineurin, JNK, p38 MAPK, or MEK.
      These results localize the decision point in positive vs negative selection to a
      step downstream of Ca(2+) signaling and suggest that negative selection signals
      induce Ca(2+)-dependent bim transcription through PKC.

PMID- 16455987
TI  - CD4-dependent potentiation of a high molecular weight-melanoma-associated antigen
      specific CTL response elicited in HLA-A2/Kb transgenic mice.
AB  - The human high m.w.-melanoma-associated Ag (HMW-MAA) is an attractive target for
      the immunotherapy of melanoma, due to its relatively high expression in a high
      percentage of melanoma lesions and its restricted distribution in normal tissues.
      Active immunization with HMW-MAA mimics has been previously shown to induce a HMW
      MAA-specific, T cell-dependent Ab response associated with an apparent clinically
      beneficial effect in advanced melanoma patients. Although T cells play an
      important role in controlling tumor growth, only limited information is available
      to date about the induction of HMW-MAA-specific CTL. In this report, we show that
      immunization of HLA-A2/K(b) transgenic mice with HMW-MAA cDNA-transfected
      syngeneic dendritic cells elicited a CD8(+) CTL response specific for HMW-MAA
      peptides with HLA-A2 Ag-binding motifs. The elicited CTL lysed HLA-A2(+)HMW
      MAA(+) melanoma cells in vitro, and mouse HLA-A2/K(b) cells pulsed with HMW-MAA
      derived peptides in vitro and in vivo. Although this CTL response could be
      generated in the absence of CD4(+) T cell help, harnessing CD4(+) T cell help in
      a noncognate Ag-specific manner with the polyclonal activator staphylococcal
      enterotoxin A augmented the CTL response. These results imply that dendritic cell
      based immunization, in combination with CD4(+) T cell help, represents an
      effective strategy to implement T cell-based immunotherapy targeting HMW-MAA in
      patients with HMW-MAA-bearing tumors.

PMID- 16455988
TI  - Effector and memory CD8+ T cells can be generated in response to alloantigen
      independently of CD4+ T cell help.
AB  - There is now considerable evidence suggesting that CD8(+) T cells are able to
      generate effector but not functional memory T cells following pathogenic
      infections in the absence of CD4(+) T cells. We show that following
      transplantation of allogeneic skin, in the absence of CD4(+) T cells, CD8(+) T
      cells become activated, proliferate, and expand exclusively in the draining lymph
      nodes and are able to infiltrate and reject skin allografts. CD44(+)CD8(+) T
      cells isolated 100 days after transplantation rapidly produce IFN-gamma following
      restimulation with alloantigen in vitro. In vivo CD44(+)CD8(+) T cells rejected
      donor-type skin allografts more rapidly than naive CD8(+) T cells demonstrating
      the ability of these putative memory T cells to mount an effective recall
      response in vivo. These data form the first direct demonstration that CD8(+) T
      cells are able to generate memory as well as effector cells in response to
      alloantigen during rejection in the complete absence of CD4(+) T cells. These
      data have important implications for the design of therapies to combat rejection
      and serve to reinforce the view that CD8(+) T cell responses to allografts
      require manipulation in addition to CD4(+) T cell responses to completely prevent
      the rejection of foreign organ transplants.

PMID- 16455989
TI  - Frequency of natural regulatory CD4+CD25+ T lymphocytes determines the outcome of
      tolerance across fully mismatched MHC barrier through linked recognition of self
      and allogeneic stimuli.
AB  - We show in this study that long-term tolerance to allogeneic skin grafts can be
      established in the absence of immunosuppression by the combination of the
      following elements: 1) augmenting the frequency of regulatory CD4(+)CD25(+) T
      cells (Treg) and 2) presentation of the allogeneic stimuli through linked
      recognition of allo- and self-epitopes on semiallogeneic F(1) APCs. BALB/c spleen
      cells enriched for CD4(+)CD25(+) T lymphocytes were transferred either to BALB/c
      nu/nu mice or to BALB/c nu/nu previously injected with F(1)(BALB/c x B6.Ba)
      spleen cells, or else grafted with F(1)(BALB/c x B6.Ba) skin (chimeric BALB/c
      nu/nu-F(1)). Chimeric BALB/c nu/nu-F(1) reconstituted with syngeneic CD25(+)
      enriched spleen cells were unable to reject the previously transferred
      F(1)(BALB/c x B6.Ba) spleen cells or F(1)(BALB/c x B6.Ba) skin grafts, and a
      specific tolerance to a secondary B6 graft was obtained, with rejection of third
      party CBA grafts. BALB/c nu/nu mice reconstituted only with syngeneic CD25(+)
      enriched spleen cells rejected both B6 and CBA skin grafts. In contrast, when
      chimeric BALB/c nu/nu-F(1) were reconstituted with spleen populations comprising
      normal frequencies of Treg cells, the linked recognition of allo and self
      resulted in breaking of self tolerance and rejection of syngeneic grafts,
      strongly suggesting that linked recognition works in both directions, either to
      establish tolerance to allo, or to break tolerance to self, the critical
      parameter being the relative number of Treg cells.

PMID- 16455990
TI  - Ex vivo characterization of allo-MHC-restricted T cells specific for a single MHC
      peptide complex.
AB  - Alloreactive T cells are thought to be a potentially rich source of high-avidity
      T cells with therapeutic potential since tolerance to self-Ags is restricted to
      self-MHC recognition. Given the particularly high frequency of alloreactive T
      cells in the peripheral immune system, we used numerous MHC class I multimers to
      directly visualize and isolate viral and tumor Ag-specific alloreactive CD8 T
      cells. In fact, all but one specificities screened were undetectable in ex vivo
      labeling. In this study, we report the occurrence of CD8 T cells specifically
      labeled with allo-HLA-A*0201/Melan-A/MART-1(26-35) multimers at frequencies that
      are in the range of 10(-4) CD8 T cells and are thus detectable ex vivo by flow
      cytometry. We report the thymic generation and shaping of tumor Ag-specific,
      alloreactive T cells as well as their fate once seeded in the periphery. We show
      that these cells resemble their counterparts in HLA-A*0201-positive individuals,
      based on their structural and functional attributes.

PMID- 16455991
TI  - Chemokine receptor CXCR3 desensitization by IL-16/CD4 signaling is dependent on
      CCR5 and intact membrane cholesterol.
AB  - Previous work has shown that IL-16/CD4 induces desensitization of both CCR5- and
      CXCR4-induced migration, with no apparent effect on CCR2b or CCR3. To investigate
      the functional relationship between CD4 and other chemokine receptors, we
      determined the effects of IL-16 interaction with CD4 on CXCR3-induced migration.
      In this study we demonstrate that IL-16/CD4 induced receptor desensitization of
      CXCR3 on primary human T cells. IL-16/CD4 stimulation does not result in surface
      modulation of CXCR3 or changes in CXCL10 binding affinity. This effect does
      require p56(lck) enzymatic activity and the presence of CCR5, because
      desensitization is not transmitted in the absence of CCR5. Treatment of human T
      cells with methyl-beta-cyclodextrin, a cholesterol chelator, prevented the
      desensitization of CXCR3 via IL-16/CD4, which was restored after reloading of
      cholesterol, indicating a requirement for intact cholesterol. These studies
      demonstrate an intimate functional relationship among CD4, CCR5, and CXCR3, in
      which CCR5 can act as an adaptor molecule for CD4 signaling. This process of
      regulating Th1 cell chemoattraction may represent a mechanism for orchestrating
      cell recruitment in Th1-mediated diseases.

PMID- 16455992
TI  - CCL5 modulates pneumococcal immunity and carriage.
AB  - Understanding the requirements for protection against pneumococcal carriage and
      pneumonia will greatly benefit efforts in controlling these diseases. Recently,
      it has been shown that genetic polymorphisms can result in diminished expression
      of CCL5, which results in increased susceptibility to and progression of
      infectious diseases. We show that CCL5, together with Th cytokine mRNA
      expression, is temporally up-regulated during pneumococcal carriage. To determine
      the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and
      cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs
      before and during Streptococcus pneumoniae strain EF3030-challenge for the
      initiation of carriage. CCL5 blockade resulted in a decrease of CD4(+) and CD8(+)
      T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and
      nasopharyngeal associated lymphoid tissue during the recognition phase of the
      pneumococcal adaptive immune response. CCL5 blockade significantly reduced the Ag
      specific IgG2a and IgG1 Abs in serum and IgA Ab levels in nasal washes. These
      decreases also corresponded to reductions in Ag-specific T cell (mucosal and
      systemic) responses. CCL5 inhibition resulted in decreasing the quantity of IL-4-
      and IFN-gamma-secreting CD4(+) T cells and increasing the number of Ag-specific
      IL-10-producing CD4(+) T cells; these changes combined also corresponded with the
      transition from pneumococcal carriage to lethal pneumonia. These data suggest
      that CCL5 is an essential factor for the induction and maintenance of protective
      pneumococcal immunity.

PMID- 16455993
TI  - Langerhans-type dendritic cells genetically modified to express full-length
      antigen optimally stimulate CTLs in a CD4-dependent manner.
AB  - Oncoretroviral vectors encoding either full-length Ag or a corresponding
      immunodominant peptide were expressed in Langerhans-type dendritic cells (LCs)
      differentiated from CD34(+) progenitors. We used human CMV as a model Ag
      restricted by HLA-A*0201 to define parameters for eventual expression of cancer
      Ags by LCs for active immunization against tumors. Stimulation by CMVpp65(495
      503)-pulsed LCs, CMVpp65(495-503)-transduced LCs, and full-length CMVpp65
      transduced LCs respectively increased tetramer-reactive T cells with an effector
      memory phenotype by 10 +/- 11, 34 +/- 21, and 51 +/- 24-fold (p < 0.05) from CMV
      seropositive donors. CMV-specific CD8(+) CTLs achieved respective frequencies of
      231 +/- 102, 583 +/- 219, and 714 +/- 281 spot-forming cells per 10(5) input
      cells (p < 0.01) in ELISPOT assays for IFN-gamma secretion. LCs expressing full
      length Ag stimulated greater lytic activity than either peptide-transduced or
      peptide-pulsed LCs (p < 0.05), all in the absence of exogenous cytokines. pp65
      transduced LCs presenting class I and II MHC-restricted epitopes expanded IFN
      gamma-secreting CD4(+) T cells, whereas pp65(495-503)-transduced LCs did not.
      CD4(+) T cell numbers even declined after stimulation by pp65(495-503) peptide
      pulsed LCs. CD4(+) T cell depletion confirmed their contribution to the more
      robust CTL responses. LCs, transduced with a retroviral vector encoding full
      length Ag, stimulate potent CTLs directed against multiple epitopes in a CD4(+)
      Th cell-dependent manner.

PMID- 16455994
TI  - A polymeric bacterial protein activates dendritic cells via TLR4.
AB  - The enzyme lumazine synthase from Brucella spp. (BLS) is a highly immunogenic
      protein that folds as a stable dimer of pentamers. It is possible to insert
      foreign peptides and proteins at the 10 N terminus of BLS without disrupting its
      general folding, and these chimeras are very efficient to elicit systemic and
      oral immunity without adjuvants. In this study, we show that BLS stimulates bone
      marrow dendritic cells from mice in vitro to up-regulate the levels of
      costimulatory molecules (CD40, CD80, and CD86) and major histocompatibility class
      II Ag. Furthermore, the mRNA levels of several chemokines are increased, and
      proinflammatory cytokine secretion is induced upon exposure to BLS. In vivo, BLS
      increases the number of dendritic cells and their expression of CD62L in the
      draining lymph node. All of the observed effects are dependent on TLR4, and
      clearly independent of LPS contamination. The described characteristics of BLS
      make this protein an excellent candidate for vaccine development.

PMID- 16455995
TI  - Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling.
AB  - TLR2 plays a key role in the initiation of the cellular innate immune responses
      by a wide range of bacterial products. TLRs signaling, including TLR2 and its
      coreceptors TLR1 and TLR6, is mediated by a number of specific ligands. Although
      many of the TLR-mediated cell signaling pathways have been elucidated in the past
      few years, the molecular mechanisms that lead to cell activation are still poorly
      understood. In this study, we investigate the interaction of PorB from Neisseria
      meningitidis with TLR2 and describe the direct binding of a bacterial protein to
      TLR2 for the first time. Using labeled PorB, we demonstrate its binding to TLR2
      both in its soluble form in vitro, and when it is over-expressed on the surface
      of human embryonic kidney 293 cells. We also show that TLR2-mediated binding of
      PorB is directly related to cellular activation. In addition, using 293 cells
      expressing the chimeric TLR2/TLR1 and TLR2/TLR6 complexes, we report the
      selectivity of PorB binding to the TLR2/TLR1 heterodimer, which is required for
      initiating signaling in transfected 293 cells and in murine B cells. Together,
      these data provide new evidence that TLR2 recognizes PorB through direct binding,
      and that PorB-induced cell activation is mediated by a TLR2/TLR1 complex.

PMID- 16455996
TI  - Position-dependent repression and promotion of DQB1 intron 3 splicing by GGGG
      motifs.
AB  - Alternative splicing of HLA-DQB1 exon 4 is allele-dependent and results in
      variable expression of soluble DQbeta. We have recently shown that differential
      inclusion of this exon in mature transcripts is largely due to intron 3 variants
      in the branch point sequence (BPS) and polypyrimidine tract. To identify
      additional regulatory cis-elements that contribute to haplotype-specific splicing
      of DQB1, we systematically examined the effect of guanosine (G) repeats on intron
      3 removal. We found that the GGG or GGGG repeats generally improved splicing of
      DQB1 intron 3, except for those that were adjacent to the 5' splice site where
      they had the opposite effect. The most prominent splicing enhancement was
      conferred by GGGG motifs arranged in tandem upstream of the BPS. Replacement of a
      G-rich segment just 5' of the BPS with a series of random sequences markedly
      repressed splicing, whereas substitutions of a segment further upstream that
      lacked the G-rich elements and had the same size did not result in comparable
      splicing inhibition. Systematic mutagenesis of both suprabranch guanosine
      quadruplets (G(4)) revealed a key role of central G residues in splicing
      enhancement, whereas cytosines in these positions had the most prominent
      repressive effects. Together, these results show a significant role of tandem
      G(4)NG(4) structures in splicing of both complete and truncated DQB1 intron 3,
      support position dependency of G repeats in splicing promotion and inhibition,
      and identify positively and negatively acting sequences that contribute to the
      haplotype-specific DQB1 expression.

PMID- 16455997
TI  - B cell-specific deficiency for Smad2 in vivo leads to defects in TGF-beta
      directed IgA switching and changes in B cell fate.
AB  - Smad2 is a member of the intracellular mediators that transduce signals from TGF
      beta receptors and activin receptors. Targeted inactivation of Smad2 in mice
      leads to early lethality before gastrulation. It was shown previously that TGF
      betaRII deficiency in vivo leads to defects in B cell homeostasis, Ag
      responsiveness, and IgA class switch recombination of B cells. To investigate the
      importance of Smad2-mediated signaling in B lymphocytes, we generated a B cell
      specific inactivation of Smad2 in mice (bSmad2(-/-)). bSmad2(-/-) mice had normal
      B cell numbers in the spleen but showed a reduced population of marginal zone B
      cells. In contrast, B cells in Peyer's patches and peritoneal B-1a cells of
      bSmad2(-/-) mice were increased in numbers. bSmad2(-/-) mice showed a reduced
      number of surface-IgA(+) B cells and of IgA-secreting cells in Peyer's patches,
      decreased levels of IgA in serum, and, after immunization with a T cell-dependent
      Ag, a reduced IgA response. Class switch recombination to IgA was impaired in
      Smad2-deficient B cells, when stimulated in vitro with LPS in the presence of TGF
      beta. The growth-inhibitory effects of TGF-beta in LPS-stimulated B cells were
      not affected in Smad2-deficient B cells. In summary, our data indicate a crucial
      role of Smad2 in mediating signals for the TGF-beta-directed class switch to IgA
      and the induction of IgA responses in vivo. Other B cell functions like growth
      inhibitory signaling, which are known to be regulated by signals via the TGF
      betaR, are not affected in Smad2-deficient B cells.

PMID- 16455998
TI  - CD161 (human NKR-P1A) signaling in NK cells involves the activation of acid
      sphingomyelinase.
AB  - NK and NKT cells play a major role in both innate immunity and in influencing the
      development of adaptive immune responses. CD161 (human NKR-P1A), a protein
      encoded in the NK gene complex, is a major phenotypic marker of both these cell
      types and is thought to be involved in the regulation of NK and NKT cell
      function. However, the mechanisms of action and signaling pathways of CD161 are
      poorly understood. To identify molecules able to interact with the cytoplasmic
      tail of human CD161 (NKR-P1A), we have conducted a yeast two-hybrid screen and
      identified acid sphingomyelinase as a novel intracellular signaling pathway
      linked to CD161. mAb-mediated cross-linking of CD161, in both transfectants and
      primary human NK cells, triggers the activation of acid, but not neutral
      sphingomyelinase. The sphingomyelinases represent the catabolic pathway for N
      acyl-sphingosine (ceramide) generation, an emerging second messenger with key
      roles in the induction of apoptosis, proliferation, and differentiation. These
      data therefore define a novel signal transduction pathway for the CD161 (NKR-P1A)
      receptor and provide fresh insights into NK and NKT cell biology.

PMID- 16455999
TI  - Involvement of protein kinase Cepsilon in the negative regulation of Akt
      activation stimulated by granulocyte colony-stimulating factor.
AB  - Stimulation of cells with G-CSF activates multiple signaling cascades, including
      the serine/threonine kinase Akt pathway. We show in this study that G-CSF-induced
      activation of Akt in myeloid 32D was specifically inhibited by treatment with
      PMA, a protein kinase C (PKC) activator. PMA treatment also rapidly attenuated
      sustained Akt activation mediated by a carboxy truncated G-CSF receptor,
      expressed in patients with acute myeloid leukemia evolving from severe congenital
      neutropenia. The inhibitory effect of PMA was abolished by pretreatment of cells
      with specific PKC inhibitor GF109203X, suggesting that the PKC pathway negatively
      regulates Akt activation. Ro31-8820, a PKCepsilon inhibitor, also abrogated PMA
      mediated inhibition of Akt activation, whereas rottlerin and Go6976, inhibitors
      of PKCdelta and PKCalphabetaI, respectively, exhibited no significant effects.
      Furthermore, overexpression of the wild-type and a constitutively active, but not
      a kinase-dead, forms of PKCepsilon markedly attenuated Akt activation, and
      inhibited the proliferation and survival of cells in response to G-CSF. The
      expression of PKCepsilon was down-regulated with G-CSF-induced terminal
      granulocytic differentiation. Together, these results implicate PKCepsilon as a
      negative regulator of Akt activation stimulated by G-CSF and indicate that
      PKCepsilon plays a negative role in cell proliferation and survival in response
      to G-CSF.

PMID- 16456000
TI  - Endotoxin-induced down-regulation of Elk-3 facilitates heme oxygenase-1 induction
      in macrophages.
AB  - Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is acutely induced by
      inflammatory stimuli, and the products of HO-1-mediated heme degradation have
      anti-inflammatory properties. In many different pathophysiologic states, the up
      regulation of HO-1 has been shown to be beneficial in combating the detrimental
      consequences of increased inflammation. Ets transcription factors are known to be
      important mediators of inflammatory responses, and the ternary complex factor
      subfamily of Ets proteins has both transcriptional activation and repression
      activity. The present study demonstrates that of several ternary complex factor
      subfamily members, only Elk-3 represses HO-1 promoter activity in macrophages.
      Endotoxin administration to macrophages led to a dose-dependent decrease in
      endogenous Elk-3 mRNA levels, and this reduction in Elk-3 preceded the LPS
      mediated up-regulation of HO-1 message. Analogous results also occurred in lung
      tissue of mice exposed to endotoxin. Two putative Ets binding sites (EBS1 and
      EBS2) are present in the downstream region of the murine HO-1 promoter (bp -125
      and -93, respectively), and we recently showed that the EBS2 site is essential
      for HO-1 induction by endotoxin. In contrast, the present study demonstrates that
      the repressive effect of Elk-3 on HO-1 promoter activity is dependent on the EBS1
      site. Taken together, our data reveal that Elk-3 serves as an important repressor
      of HO-1 gene transcription and contributes to the tight control of HO-1 gene
      regulation in the setting of inflammatory stimuli.

PMID- 16456001
TI  - Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit signals
      from FcepsilonRI.
AB  - Scaffolding adapter Grb2-associated binder 2 (Gab2) is a key component of
      FcepsilonRI signaling in mast cells, required for the activation of PI3K. To
      understand how Gab2 is activated in FcepsilonRI signaling, we asked which protein
      tyrosine kinase is required for Gab2 phosphorylation. We found that Gab2 tyrosyl
      phosphorylation requires Lyn and Syk. In agreement with published results, we
      found that Fyn also contributes to Gab2 tyrosyl phosphorylation. However, Syk
      activation is defective in Fyn(-/-) mast cells, suggesting that Syk is the
      proximal kinase responsible for Gab2 tyrosyl phosphorylation. Then, we asked
      which domains in Gab2 are required for Gab2 tyrosyl phosphorylation. We found
      that the Grb2-Src homology 3 (SH3) binding sites are required for, whereas the
      pleckstrin homology (PH) domain contributes to, Gab2 tyrosyl phosphorylation.
      Using a protein/lipid overlay assay, we determined that the Gab2 PH domain
      preferentially binds the PI3K lipid products, PI3, 4,5P3 and PI3, 4P2.
      Furthermore, the Grb2-SH3 binding sites and PH domain binding to PI3K lipid
      products are required for Gab2 function in FcepsilonRI-evoked degranulation and
      Akt activation. Our data strongly suggest a model for Gab2 action in FcepsilonRI
      signaling. The Grb2 SH3 binding sites play a critical role in bringing Gab2 to
      FcepsilonRI, whereupon Gab2 becomes tyrosyl-phosphorylated in a Syk-dependent
      fashion. Phosphorylated Gab2 results in recruitment and activation of PI3K, whose
      lipid products bind the PH domain of Gab2 and acts in positive feedback loop for
      sustained PI3K recruitment and phosphatidylinositol-3,4,5-trisphosphate
      production, required for FcepsilonRI-evoked degranulation of mast cells.

PMID- 16456002
TI  - Functional hierarchy of the N-terminal tyrosines of SLP-76.
AB  - The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of
      76 kDa (SLP-76) plays a central role in T cell activation and T cell development.
      SLP-76 has three functional modules: an acidic domain with three key tyrosines, a
      central proline-rich domain, and a C-terminal Src homology 2 domain. Of these,
      mutation of the three N-terminal tyrosines (Y112, Y128, and Y145) results in the
      most profound effects on T cell development and function. Y112 and Y128 associate
      with Vav and Nck, two proteins shown to be important for TCR-induced
      phosphorylation of proximal signaling substrates, Ca(2+) flux, and actin
      reorganization. Y145 has been shown to be important for optimal association of
      SLP-76 with inducible tyrosine kinase, a key regulator of T cell function. To
      investigate further the role of the phosphorylatable tyrosines of SLP-76 in TCR
      signaling, cell lines and primary T cells expressing SLP-76 with mutations in
      individual or paired tyrosine residues were analyzed. These studies show that
      Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in
      vitro and T cell development in vivo.

PMID- 16456003
TI  - Regulation of IgH gene assembly: role of the intronic enhancer and 5'DQ52 region
      in targeting DHJH recombination.
AB  - The assembly of Ag receptor genes by V(D)J recombination is regulated by
      transcriptional promoters and enhancers which control chromatin accessibility at
      Ig and TCR gene segments to the RAG-1/RAG-2 recombinase complex. Paradoxically,
      germline deletions of the IgH enhancer (Emu) only modestly reduce D(H)-->J(H)
      rearrangements when assessed in peripheral B cells. However, deletion of Emu
      severely impairs recombination of V(H) gene segments, which are located over 100
      kb away. We now test two alternative explanations for the minimal effect of Emu
      deletions on primary D(H)-->J(H) rearrangement: 1) Accessibility at the D(H)J(H)
      cluster is controlled by a redundant cis-element in the absence of Emu. One
      candidate for this element lies 5' to D(Q52) (PD(Q52)) and exhibits
      promoter/enhancer activity in pre-B cells. 2) In contrast to endpoint B cells,
      D(H)-->J(H) recombination may be significantly impaired in pro-B cells from
      enhancer-deficient mice. To elucidate the roles of PD(Q52) and Emu in the
      regulation of IgH locus accessibility, we generated mice with targeted deletions
      of these elements. We report that the defined PD(Q52) promoter is dispensable for
      germline transcription and recombination of the D(H)J(H) cluster. In contrast, we
      demonstrate that Emu directly regulates accessibility of the D(H)J(H) region.
      These findings reveal a significant role for Emu in the control mechanisms that
      activate IgH gene assembly and suggest that impaired V(H)-->D(H)J(H)
      rearrangement in enhancer-deficient cells may be a downstream consequence of the
      primary block in D(H)-->J(H) recombination.

PMID- 16456004
TI  - The molecular basis for galalpha(1,3)gal expression in animals with a deletion of
      the alpha1,3galactosyltransferase gene.
AB  - The production of homozygous pigs with a disruption in the GGTA1 gene, which
      encodes alpha1,3galactosyltransferase (alpha1,3GT), represented a critical step
      toward the clinical reality of xenotransplantation. Unexpectedly, the predicted
      complete elimination of the immunogenic Galalpha(1,3)Gal carbohydrate epitope was
      not observed as Galalpha(1,3)Gal staining was still present in tissues from
      GGTA1(-/-) animals. This shows that, contrary to previous dogma, alpha1,3GT is
      not the only enzyme able to synthesize Galalpha(1,3)Gal. As iGb3 synthase (iGb3S)
      is a candidate glycosyltransferase, we cloned iGb3S cDNA from GGTA1(-/-) mouse
      thymus and confirmed mRNA expression in both mouse and pig tissues. The mouse
      iGb3S gene exhibits alternative splicing of exons that results in a markedly
      different cytoplasmic tail compared with the rat gene. Transfection of iGb3S cDNA
      resulted in high levels of cell surface Galalpha(1,3)Gal synthesized via the
      isoglobo series pathway, thus demonstrating that mouse iGb3S is an additional
      enzyme capable of synthesizing the xenoreactive Galalpha(1,3)Gal epitope.
      Galalpha(1,3)Gal synthesized by iGb3S, in contrast to alpha1,3GT, was resistant
      to down-regulation by competition with alpha1,2fucosyltransferase. Moreover,
      Galalpha(1,3)Gal synthesized by iGb3S was immunogenic and elicited Abs in GGTA1 (
      /-) mice. Galalpha(1,3)Gal synthesized by iGb3S may affect survival of pig
      transplants in humans, and deletion of this gene, or modification of its product,
      warrants consideration.

PMID- 16456005
TI  - Modulation of the TLR-mediated inflammatory response by the endogenous human host
      defense peptide LL-37.
AB  - The sole human cathelicidin peptide, LL-37, has been demonstrated to protect
      animals against endotoxemia/sepsis. Low, physiological concentrations of LL-37 (<
      or =1 microg/ml) were able to modulate inflammatory responses by inhibiting the
      release of the proinflammatory cytokine TNF-alpha in LPS-stimulated human
      monocytic cells. Microarray studies established a temporal transcriptional
      profile and identified differentially expressed genes in LPS-stimulated monocytes
      in the presence or absence of LL-37. LL-37 significantly inhibited the expression
      of specific proinflammatory genes up-regulated by NF-kappaB in the presence of
      LPS, including NFkappaB1 (p105/p50) and TNF-alpha-induced protein 2 (TNFAIP2). In
      contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize
      inflammation, such as TNF-alpha-induced protein 3 (TNFAIP3) and the NF-kappaB
      inhibitor, NFkappaBIA, or certain chemokine genes that are classically considered
      proinflammatory. Nuclear translocation, in LPS-treated cells, of the NF-kappaB
      subunits p50 and p65 was reduced > or =50% in the presence of LL-37,
      demonstrating that the peptide altered gene expression in part by acting directly
      on the TLR-to-NF-kappaB pathway. LL-37 almost completely prevented the release of
      TNF-alpha and other cytokines by human PBMC following stimulation with LPS and
      other TLR2/4 and TLR9 agonists, but not with cytokines TNF-alpha or IL-1beta.
      Biochemical and inhibitor studies were consistent with a model whereby LL-37
      modulated the inflammatory response to LPS/endotoxin and other agonists of TLR by
      a complex mechanism involving multiple points of intervention. We propose that
      the natural human host defense peptide LL-37 plays roles in the delicate
      balancing of inflammatory responses in homeostasis as well as in combating sepsis
      induced by certain TLR agonists.

PMID- 16456006
TI  - Transepithelial pathogen uptake into the small intestinal lamina propria.
AB  - The lamina propria that underlies and stabilizes the gut lining epithelium is
      densely populated with strategically located mononuclear phagocytes.
      Collectively, these lamina propria macrophages and dendritic cells (DC) are
      believed to be crucial for tissue homeostasis as well as the innate and adaptive
      host defense. Lamina propria DC were recently shown to gain direct access to the
      intestinal lumen by virtue of epithelium-penetrating dendrites. However, the role
      of these structures in pathogen uptake remains under debate. In this study, we
      report that entry of a noninvasive model pathogen (Aspergillus fumigatus conidia)
      into the murine small intestinal lamina propria persists in the absence of either
      transepithelial dendrites or lamina propria DC and macrophages. Our results
      suggest the existence of multiple pathogen entry pathways and point at the
      importance of villus M cells in the uptake of gut lumen Ags. Interestingly,
      transepithelial dendrites seem altogether absent from the small intestine of
      BALB/c mice suggesting that the function of lamina propria DC extensions resides
      in their potential selectivity for luminal Ags, rather than in general uptake or
      gut homeostasis.

PMID- 16456007
TI  - Cytolytic CD8+ T cells directed against a cryptic epitope derived from a
      retroviral alternative reading frame confer disease protection.
AB  - Cytolytic CD8(+) T cells (CTL) are key to the immune response that controls virus
      infections and mediates disease protection. The ability of CTL to induce
      apoptosis of infected cells and/or limit viral replication is determined by
      recognition of processed viral peptide epitopes on the surface of the target
      cell. An understudied source of MHC class I-presented peptides is the aptly named
      "cryptic epitopes," defined by their nontraditional methods of generation,
      including derivation from alternative reading frames (ARFs). Although ARF-encoded
      epitopes have now been documented in a few systems, their potential functional
      relevance in vivo has been debated. In this study, we demonstrate the
      physiological significance of an ARF-derived CTL epitope in a retrovirus-induced
      disease model. We show that disease-susceptible CD8-deficient mice reconstituted
      with CTL specific for the retroviral ARF-derived SYNTGRFPPL epitope controlled an
      infection by the LP-BM5 retrovirus isolate, evidently at the level of viral
      clearance, resulting in protection of these mice from disease. These data
      indicate that ARF-derived epitopes are indeed relevant inducers of the immune
      system and demonstrate the importance of atypically generated peptides as
      functional Ag with a physiologic role in disease protection.

PMID- 16456008
TI  - Activation of invariant NKT cells by the helminth parasite schistosoma mansoni.
AB  - Mouse CD1d-restricted NKT cells, including invariant (i)NKT cells, are innate
      cells activated by glycolipid Ags and play important roles in the initiation and
      regulation of immune responses. Through their ability to promptly produce large
      amounts of Th1 and/or Th2 cytokines upon TCR engagement, iNKT cells exert crucial
      functions in the immune/inflammatory system during bacterial, protozoan, fungal,
      and viral infections. However, their roles during metazoan parasite infection,
      which are generally associated with strong Th2 responses, still remain elusive.
      In this study, we show that during the course of murine schistosomiasis, iNKT
      cells exhibit an activated phenotype and that following schistosome egg encounter
      in the liver, hepatic iNKT cells produce both IFN-gamma and IL-4 in vivo. We also
      report that schistosome egg-sensitized dendritic cells (DCs) activate, in a CD1d
      dependent manner, iNKT cells to secrete IFN-gamma and IL-4 in vitro.
      Interestingly, transfer of egg-sensitized DCs promotes a strong Th2 response in
      recipient wild-type mice, but not in mice that lack iNKT cells. Engagement of
      TLRs in DCs is not necessary for iNKT cell stimulation in response to egg
      sensitized DCs, suggesting an alternative pathway of activation. Finally, we
      propose that self, rather than parasite-derived, CD1d-restricted ligands are
      implicated in iNKT cell stimulation. Taken together, our data show for the first
      time that helminths can activate iNKT cells to produce immunoregulatory cytokines
      in vivo, enabling them to influence the adaptive immune response.

PMID- 16456009
TI  - OX40 ligation of CD4+ T cells enhances virus-specific CD8+ T cell memory
      responses independently of IL-2 and CD4+ T regulatory cell inhibition.
AB  - We have previously shown that CD4(+) T cells are required to optimally expand
      viral-specific memory CD8(+) CTL responses using a human dendritic cell-T cell
      based coculture system. OX40 (CD134), a 50-kDa transmembrane protein of the TNFR
      family, is expressed primarily on activated CD4(+) T cells. In murine models, the
      OX40/OX40L pathway has been shown to play a critical costimulatory role in
      dendritic cell/T cell interactions that may be important in promoting long-lived
      CD4(+) T cells, which subsequently can help CD8(+) T cell responses. The current
      study examined whether OX40 ligation on ex vivo CD4(+) T cells can enhance their
      ability to "help" virus-specific CTL responses in HIV-1-infected and -uninfected
      individuals. OX40 ligation of CD4(+) T cells by human OX40L-IgG1 enhanced the ex
      vivo expansion of HIV-1-specific and EBV-specific CTL from HIV-1-infected and 
      uninfected individuals, respectively. The mechanism whereby OX40 ligation
      enhanced help of CTL was independent of the induction of cytokines such as IL-2
      or any inhibitory effect on CD4(+) T regulatory cells, but was associated with a
      direct effect on proliferation of CD4(+) T cells. Thus, OX40 ligation on CD4(+) T
      cells represents a potentially novel immunotherapeutic strategy that should be
      investigated to treat and prevent persistent virus infections, such as HIV-1
      infection.

PMID- 16456010
TI  - Impaired protection against Mycobacterium bovis bacillus Calmette-Guerin
      infection in IL-15-deficient mice.
AB  - To investigate the potential role of endogenous IL-15 in mycobacterial infection,
      we examined protective immunity in IL-15-deficient (IL-15(-/-)) mice after
      infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG) or recombinant
      OVA-expressing BCG (rBCG-OVA). IL-15(-/-) mice exhibited an impaired protection
      in the lung on day 120 after BCG infection as assessed by bacterial growth.
      CD4(+) Th1 response capable of producing IFN-gamma was normally detected in
      spleen and lung of IL-15(-/-) mice on day 120 after infection. Although Ag
      specific CD8 responses capable of producing IFN-gamma and exhibiting cytotoxic
      activity were detected in the lung on day 21 after infection with rBCG-OVA, the
      responses were severely impaired on days 70 and 120 in IL-15(-/-) mice. The
      degree of proliferation of Ag-specific CD8(+) T cells in IL-15(-/-) mice was
      similar to that in wild-type mice during the course of infection with rBCG-OVA,
      whereas sensitivity to apoptosis of Ag-specific CD8(+) T cells significantly
      increased in IL-15(-/-) mice. These results suggest that IL-15 plays an important
      role in the development of long-lasting protective immunity to BCG infection via
      sustaining CD8 responses in the lung.

PMID- 16456011
TI  - Induction of enhanced immunity to intestinal nematodes using IL-9-producing
      dendritic cells.
AB  - Dendritic cells can be considered natural adjuvants and are able to act as
      cellular vaccines to protect against disease. Adoptive transfer of Ag-pulsed bone
      marrow-derived dendritic cells (BMDCs) enhanced expulsion of the intestinal
      nematode, Trichinella spiralis, from the small intestine. IL 9 is a critical
      cytokine in protective immunity to intestinal nematode infection and is believed
      to enhance Th2 immune responses. Deriving dendritic cells from an IL-9 transgenic
      (IL-9t) mouse has enabled a detailed investigation of the importance of IL-9
      during Ag presentation. Indeed, IL-9t dendritic cells significantly enhanced T
      cell proliferation and Th2 responses and, after adoptive transfer, enhanced
      parasite-specific IgG1 and intestinal mastocytosis in vivo, leading to
      accelerated expulsion of adult worms from the intestine. Overall, this paper
      demonstrates that dendritic cell vaccination can be used to successfully protect
      the host against intestinal nematode infection and suggests that IL-9 can act as
      a potent type 2 adjuvant during Ag presentation and the early stages of Th2
      activation.

PMID- 16456012
TI  - Gliadin stimulation of murine macrophage inflammatory gene expression and
      intestinal permeability are MyD88-dependent: role of the innate immune response
      in Celiac disease.
AB  - Recent studies have demonstrated the importance of TLR signaling in intestinal
      homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in
      susceptible individuals by the ingestion of gliadin-containing grains. In this
      study, we sought to test the hypothesis that gliadin initiates this response by
      stimulating the innate immune response to increase intestinal permeability and by
      up-regulating macrophage proinflammatory gene expression and cytokine production.
      To this end, intestinal permeability and the release of zonulin (an endogenous
      mediator of gut permeability) in vitro, as well as proinflammatory gene
      expression and cytokine release by primary murine macrophage cultures, were
      measured. Gliadin and its peptide derivatives, 33-mer and p31-43, were found to
      be potent inducers of both a zonulin-dependent increase in intestinal
      permeability and macrophage proinflammatory gene expression and cytokine
      secretion. Gliadin-induced zonulin release, increased intestinal permeability,
      and cytokine production were dependent on myeloid differentiation factor 88
      (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were
      neither TLR2- nor TLR4-dependent. Our data support the following model for the
      innate immune response to gliadin in the initiation of CD. Gliadin interaction
      with the intestinal epithelium increases intestinal permeability through the
      MyD88-dependent release of zonulin that, in turn, enables paracellular
      translocation of gliadin and its subsequent interaction with macrophages within
      the intestinal submucosa. There, the interaction of gliadin with macrophages
      elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the
      interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive
      immune response seen in patients with CD.

PMID- 16456013
TI  - Proinflammatory cytokine production in liver regeneration is Myd88-dependent, but
      independent of Cd14, Tlr2, and Tlr4.
AB  - TNF and IL-6 are considered to be important to the initiation or priming phase of
      liver regeneration. However, the signaling pathways that lead to the production
      of these cytokines after partial hepatectomy (PH) have not been identified.
      Enteric-derived LPS appears to be important to liver regeneration, possibly by
      stimulating proinflammatory cytokine production after surgery. To determine
      whether LPS signaling pathways are involved in the regulation of the
      proinflammatory cytokines TNF and IL-6 during the priming phase of liver
      regeneration, we performed PH on mice lacking the TLRs Tlr4 and Tlr2, the LPS
      coreceptor, Cd14, and Myd88, an adapter protein involved in most TLR and IL-1R
      pathways. In MyD88 knockout (KO) mice after PH, both liver Tnf mRNA and
      circulating IL-6 levels were severely depressed compared with heterozygous or
      wild-type mice. Activation of STAT-3 and three STAT-3 responsive genes, Socs3,
      Cd14, and serum amyloid A2 were also blocked. In contrast, Tlr4, Tlr2, and Cd14
      KO mice showed no deficits in the production of IL-6. Surprisingly, none of these
      KO mice showed any delay in hepatocyte replication. These data indicate that the
      LPS receptor TLR4, as well as TLR2 and CD14, do not play roles in regulating
      cytokine production or DNA replication after PH. In contrast, MyD88-dependent
      pathways appear to be responsible for TNF, IL-6, and their downstream signaling
      pathways.

PMID- 16456014
TI  - Priming of glomerular mesangial cells by activated macrophages causes blunted
      responses to proinflammatory stimuli.
AB  - Macrophage-mesangial cell interaction plays a crucial role in the pathogenesis of
      glomerulonephritis. Activated macrophages trigger mesangial cells to express an
      array of inflammation-associated genes via activation of NF-kappaB and AP-1.
      However, this inflammatory response is often transient and subsides
      spontaneously. We found that mesangial cells activated by bystander macrophages
      showed blunted responses of NF-kappaB to subsequent macrophage exposure. It was
      associated with sustained levels of IkappaBbeta, but not IkappaBalpha. The
      tolerance observed was reversible and reproduced by conditioned media from
      activated macrophages (macrophage-conditioned medium (MphiCM)). In vivo priming
      of mesangial cells by activated glomerular macrophages also caused the tolerance
      of mesangial cells. The macrophage-derived tolerance inducers were heat-labile,
      and multiple molecules were involved. Among inflammatory cytokines produced by
      macrophages, TNF-alpha and IL-1beta were able to induce mesangial cell tolerance
      dose-dependently. The mesangial cell tolerance was also observed in activation of
      the MAPK-AP-1 pathway; i.e., phosphorylation of ERK, JNK, and p38 MAPK by
      macrophages was blunted when the cells were pre-exposed to MphiCM. Induction of c
      fos and c-jun was also abrogated in mesangial cells pre-exposed to MphiCM, and
      the suppression was attenuated by blockade of MAPK activation during the first
      exposure to MphiCM. These data elucidated that mesangial cells, once exposed to
      macrophages, become insensitive to subsequent activation by macrophages and
      proinflammatory stimuli. This self defense of glomerular cells may play a role in
      the resolution of macrophage-mediated, acute glomerulonephritis.

PMID- 16456015
TI  - Neutrophils regulate airway responses in a model of fungal allergic airways
      disease.
AB  - Neutrophils infiltrate airway walls in patients with allergic airway diseases and
      in animal models of these illnesses, but their contribution to the pathogenesis
      of airway allergy is not established. We hypothesized that, in a mouse model of
      airway allergy to the ubiquitous environmental mold, Aspergillus fumigatus,
      airway neutrophils contribute to disease severity. Ab-mediated neutrophil
      depletion resulted in reduced airway hyperresponsiveness and remodeling, whereas
      conditional transgenic overexpression of the neutrophil chemotactic molecule,
      CXCL1, in airway walls resulted in worsened allergic responses. This worsened
      phenotype was associated with a marked increase in the number of airway
      neutrophils but not other lung leukocytes, including eosinophils and lymphocyte
      subsets, and depletion of neutrophils in sensitized mice with transgenic
      overexpression of CXCL1 resulted in attenuated airway responses. The number of
      lung neutrophils correlated with lung matrix metalloproteinase 9 (MMP-9) activity
      both in the context of neutrophil depletion and with augmented neutrophil
      recruitment to the airways. Although wild-type and MMP-9-deficient neutrophils
      homed to the inflamed airways to a similar extent, transfer of wild-type, but not
      MMP-9-deficient, neutrophils to MMP-9-deficient animals resulted in augmented
      allergic airway responses. Taken together, these data implicate neutrophils in
      the pathogenesis of fungal allergic airway disease.

PMID- 16456016
TI  - Impaired GATA3-dependent chromatin remodeling and Th2 cell differentiation
      leading to attenuated allergic airway inflammation in aging mice.
AB  - Age-related changes in lymphocytes are most prominent in the T cell compartment.
      There have been substantial numbers of reports on T cell function in aged mice
      and humans, such as on the production of Th1 and Th2 cytokines, but the results
      show considerable variation and contradictions. In the present study, we used 8-
      to 12-mo-old aging mice and a well-established in vitro Th1/Th2 cell
      differentiation culture system to identify molecular defects in Th1/Th2 cell
      differentiation that can be detected in the relatively early stages of aging. The
      capability to differentiate into Th2 cells is reduced in aging mouse CD4(+) T
      cells. Decreased activation of the ERK MAPK cascade upon TCR stimulation, but
      normal intracellular-free calcium ion concentration mobilization and normal IL-4
      induced STAT6 activation were observed in aging mouse CD4(+) T cells. In
      addition, reduced expression of GATA3 was detected in developing Th2 cells.
      Chromatin remodeling of the Th2 cytokine gene locus was found to be impaired. Th2
      dependent allergic airway inflammation was milder in aging mice compared with in
      young adult mice. These results suggest that the levels of Th2 cell
      differentiation and resulting Th2-dependent immune responses, including allergic
      airway inflammation, decline during aging through defects in the activation of
      the ERK MAPK cascade, expression of GATA3 protein and GATA3-dependent chromatin
      remodeling of the Th2 cytokine gene locus. In the present study, we provide the
      first evidence indicating that a chromatin-remodeling event in T cells is
      impaired by aging.

PMID- 16456017
TI  - Involvement of group VIA calcium-independent phospholipase A2 in macrophage
      engulfment of hydrogen peroxide-treated U937 cells.
AB  - Hydrogen peroxide-induced apoptosis of U937 cells results in substantial
      hydrolysis of membrane phospholipids by calcium-independent group VIA
      phospholipase A(2) (iPLA(2)-VIA). However, abrogation of cellular iPLA(2)-VIA
      neither delays nor decreases apoptosis, suggesting that, beyond a mere
      destructive role, iPLA(2)-VIA may serve other specific roles. In this study, we
      report that phagocytosis of apoptosing U937 cells by macrophages is blunted if
      the cells are depleted of iPLA(2)-VIA by treatment with an inhibitor or an
      antisense oligonucleotide, and it is augmented by overexpression of iPLA(2)-VIA
      in the dying cells. Thus, the magnitude of macrophage phagocytosis correlates
      with the level of iPLA(2)-VIA activity of the dying cells. Eliminating by
      antisense oligonucleotide technology of cytosolic group IVA phospholipase A(2)
      does not attenuate phagocytosis of U937 dying cells by macrophages. Incubation of
      U937 cells with different fatty acids has no effect on either the extent of
      hydrogen peroxide-induced apoptosis or the degree of phagocytosis of the dying
      cells by macrophages. However, preincubation of the macrophages with
      lysophosphatidylcholine before exposing them to the dying cells blocks
      phagocytosis of the latter. These results indicate that formation of
      lysophosphatidylcholine by iPLA(2)-VIA in hydrogen peroxide-treated U937 cells to
      induce apoptosis directly contributes to their efficient clearance by
      macrophages.

PMID- 16456018
TI  - Deletion of CCR1 attenuates pathophysiologic responses during respiratory
      syncytial virus infection.
AB  - The role of chemokines in chronic inflammatory responses are central to the
      recruitment of particular subsets of leukocytes. In the present studies, we have
      examined the role of CCR1 in the developing pathogenesis of respiratory syncytial
      virus (RSV) in the lungs of infected BALB/c mice. Although we did not observe
      significant differences in clearance of RSV, we were able to identify decreased
      pathophysiologic responses in CCR1(-/-) mice. CCR1(-/-) mice displayed a
      significant reduction in both airway hyperresponsiveness and mucus production
      that corresponded to significant increases in IFN-gamma and CXCL10. The goblet
      cell hyper/metaplasia and the expression of mucus-associated gene, gob5, were
      correspondingly reduced in the CCR1(-/-) mice. In addition, the Western blot
      analysis of gob5 protein indicated that CCR1(-/-) mice have virtually no up
      regulation of the protein at day 6 of infection compared with wild-type-infected
      mice. Results from bone marrow chimeric mice indicated that partial
      reconstitution of the response could be achieved in the CCR1(-/-) mice with wild
      type bone marrow cells, suggesting that these cells have a role in the response.
      However, transplanting of CCR1(-/-) bone marrow into wild-type mice did
      demonstrate an incomplete deficit in RSV-induced responses, indicating that
      CCR1(+) parenchymal cells may also play a significant role in the process. Thus,
      the presence of CCR1 appears to have a significant role in the development of
      detrimental airway physiologic responses during RSV infection. These data suggest
      that CCR1 may be a potential target during detrimental pulmonary responses during
      infection.

PMID- 16456019
TI  - Inhalation tolerance is induced selectively in thoracic lymph nodes but executed
      pervasively at distant mucosal and nonmucosal tissues.
AB  - Under immunogenic conditions, both the site of initial Ag exposure and consequent
      T cell priming in specific draining lymph nodes (LNs) imprint the ensuing immune
      response with lasting tissue-selective tropism. With respect to immune tolerance,
      whether the site of tolerance induction leads to compartmentalized or,
      alternatively, pervasive tolerance has not been formally investigated. Using a
      murine model of inhalation tolerance, we investigated whether the induction of
      respiratory mucosal tolerance precludes the development of de novo Th2
      sensitization upon subsequent exposure to the same Ag at distant mucosal (gut)
      and nonmucosal (cutaneous) sites. By tracking the proliferation of CFSE-labeled
      OVA-TCR transgenic CD4(+) T cells upon OVA inhalation in vivo, we defined the
      site of tolerance induction to be restricted to the thoracic LNs. Expectedly,
      inhalation tolerance prevented de novo Th2 sensitization upon subsequent exposure
      to the same Ag at the same site. Importantly, although gut- and skin-draining LNs
      were not used during tolerance induction, de novo Ag-specific proliferation and
      Th2 differentiation in these LNs, as well as memory/effector Th2 responses in the
      gut (allergic diarrhea) and skin (late-phase cutaneous responses) were inhibited
      upon immunogenic challenge to the same Ag. Interestingly, this pervasive
      tolerogenic phenotype was not associated with the presence of suppressive
      activity throughout the lymphatics; indeed, potent suppressive activity was
      detected solely in the spleen. These data indicate that while inhalation
      tolerance is selectively induced in local thoracic LNs, its tolerogenic activity
      resides systemically and leads to pervasive immune tolerance in distant mucosal
      and nonmucosal sites.

PMID- 16456020
TI  - Epithelial CXCR3-B regulates chemokines bioavailability in normal, but not in
      Sjogren's syndrome, salivary glands.
AB  - Expression of CXCR3-targeting chemokines have been demonstrated in several
      diseases, suggesting a critical role for CXCR3 in recruiting activated T cells to
      sites of immune-mediated inflammation. Sjogren's syndrome (SS) is an autoimmune
      disease characterized by a mononuclear cell infiltrate of activated T cells
      around the duct in the salivary gland. Analysis of minor salivary gland biopsy
      specimens from 20 healthy subjects and 18 patients with primary SS demonstrated
      that CXCR3, in particular, the B form of this receptor, is constitutively
      expressed by human salivary gland epithelial cells. Salivary gland epithelial
      cell cultures demonstrated that CXCR3 participate in removing relevant amount of
      agonists from the supernatant of exposed cells without mediating calcium flux or
      chemotaxis while retaining the ability to undergo internalization. Although in
      normal salivary gland epithelial cells, CXCR3 behaves as a chemokine-scavenging
      receptor, its role in SS cells is functionally impaired. The impairment of this
      scavenging function might favor chemotaxis, leading to heightened immigration of
      CXCR3-positive T lymphocytes. These findings suggest that epithelial CXCR3 may be
      involved in postsecretion regulation of chemokine bioavailability. They also
      support a critical role for CXCR3 in the pathogenesis of SS and identify its
      agonists as potential therapeutic targets.

PMID- 16456022
TI  - The shaving reaction: rituximab/CD20 complexes are removed from mantle cell
      lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes.
AB  - Clinical investigations have revealed that infusion of immunotherapeutic mAbs
      directed to normal or tumor cells can lead to loss of targeted epitopes, a
      phenomenon called antigenic modulation. Recently, we reported that rituximab
      treatment of chronic lymphocytic leukemia patients induced substantial loss of
      CD20 on B cells found in the circulation after rituximab infusion, when rituximab
      plasma concentrations were high. Such antigenic modulation can severely
      compromise therapeutic efficacy, and we postulated that B cells had been stripped
      (shaved) of the rituximab/CD20 complex by monocytes or macrophages in a reaction
      mediated by FcgammaR. We developed an in vitro model to replicate this in vivo
      shaving process, based on reacting rituximab-opsonized CD20(+) cells with
      acceptor THP-1 monocytes. After 45 min at 37 degrees C, rituximab and CD20 are
      removed from opsonized cells, and both are demonstrable on acceptor THP-1 cells.
      The reaction occurs equally well in the presence and absence of normal human
      serum, and monocytes isolated from peripheral blood also promote shaving of CD20
      from rituximab-opsonized cells. Tests with inhibitors and use of F(ab')(2) of
      rituximab indicate transfer of rituximab/CD20 complexes to THP-1 cells is
      mediated by FcgammaR. Antigenic modulation described in previous reports may have
      been mediated by such shaving, and our findings may have profound implications
      for the use of mAbs in the immunotherapy of cancer.

PMID- 16456021
TI  - Ceramide-dependent regulation of human epidermal keratinocyte CD1d expression
      during terminal differentiation.
AB  - Human keratinocytes (KC), when cultured under conditions to remain
      undifferentiated or to terminally differentiate, changed their cellular
      distribution of CD1d. As studied by confocal microscopy, undifferentiated KC had
      a pool of cytoplasmic CD1d, whereas after terminal differentiation, this molecule
      localized in the cell membrane, which recapitulates CD1d expression in vivo. A
      comparison of undifferentiated and differentiated cultured KC did not reveal any
      differences in the association with beta(2)-microglobulin, invariant chain of
      class II MHC, or patterns of glycosylation, suggesting that these biochemical
      properties are not regulating the cellular distribution of CD1d. Time-course
      studies of CD1d gene expression indicated that KC slowly increased gene
      expression with CaCl(2)-induced terminal differentiation. Increased CD1d gene
      expression was dependent on ceramide synthesis, because fumonisin B1, a ceramide
      synthetase inhibitor, blocked the increase in CD1d gene expression during
      terminal differentiation. Similarly, exogenous ceramide or the ceramidase
      inhibitor, B13, induced CD1d gene expression by undifferentiated, but not
      terminally differentiated, KC. A protein kinase C-zeta (PKC-zeta) inhibitor (a
      pseudosubstrate oligopeptide), but not a PKC-alphabeta inhibitor, significantly
      decreased CD1d gene expression by undifferentiated or ceramide-stimulated
      cultured, undifferentiated KC. As expected, downstream signaling events of PKC
      zeta (JNK phosphorylation and NF-kappaBeta accumulation in the nucleus) were also
      attenuated. The calcineurin phosphatase inhibitor cyclosporine A, which blocks KC
      terminal differentiation, also blocked CD1d gene expression by cultured KC. In
      conclusion, this novel function of cellular ceramides extends the importance of
      this class of biologically active lipids beyond that of terminal differentiation
      and barrier function in normal human skin.

PMID- 16456023
TI  - Human NK cells positively regulate gammadelta T cells in response to
      Mycobacterium tuberculosis.
AB  - The decrease in NK cell activity and the loss of gammadelta T cells in active
      pulmonary tuberculosis patients have been reported. In this study, we observed
      that the proliferating response of gammadelta T cells to the heat-treated Ags of
      Mycobacterium tuberculosis from different individuals was noted to be dependent
      on the content or function of NK cells in PBMC in a population study. We also
      found that NK cells were directly rapidly activated by the heat-treated Ags from
      M. tuberculosis (H37Ra) in vitro; in turn, the activated NK cells improved
      gammadelta T cell proliferation both by CD54-mediated cell-cell contact through
      the forming immune synapse and by soluble factors TNF-alpha, GM-CSF, and IL-12,
      but not IFN-gamma. Our results demonstrated that an interaction between NK cells
      and gammadelta T cells existed in antituberculosis immunity. Up-regulating the
      function of NK cells might be beneficial to the prevention and control of
      pulmonary tuberculosis.

PMID- 16456024
TI  - TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal
      microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn's
      disease.
AB  - The CD40/CD40 ligand (CD40L) pathway is involved in Crohn's disease (CD)
      pathogenesis. In the patients' circulation, soluble CD40L (sCD40L) levels are
      elevated and surface CD40L is increased in platelets and T cells, whereas in the
      intestine CD40 is overexpressed in the microvasculature and CD40L in platelets
      and T cells. The therapeutic effects of infliximab in CD are attributed to its
      systemic anti-TNF-alpha action, but because TNF-alpha modulates both CD40 and
      CD40L, we investigated whether infliximab affects the CD40/CD40L pathway in the
      intestine. Eighteen CD patients were evaluated before and after infliximab
      therapy. Plasma sCD40L was measured by ELISA and platelet and peripheral blood T
      cell (PBT) CD40L expression by flow cytometry. Microvascular CD40 and VCAM-1
      expression were assessed in mucosal biopsies by immunohistochemistry and by flow
      cytometry in human intestinal microvascular endothelial cells (HIMEC). Cell
      cultures were performed in the presence and absence of infliximab. Infliximab
      treatment significantly reduced plasma sCD40L levels and eliminated CD40 and VCAM
      1 from mucosal microvessels. In vitro infliximab prevented TNF-alpha-induced CD40
      and VCAM-1 expression by HIMEC, and reduced PBT, but not platelet, surface CD40L
      expression and sCD40L release. In addition, infliximab decreased T cell-induced
      VCAM-1 expression in HIMEC by down-regulating CD40L in T cells and promoting T
      cells apoptosis. These findings point to a novel mechanism of action of
      infliximab, i.e., the disruption of CD40/CD40L-dependent cognate interactions
      between intestinal microvessels and T cells. Thus, in addition to neutralizing
      TNF-alpha and inducing T cell death, the therapeutic effects of infliximab in CD
      appear to be also mediated by inhibition of vascular inflammation in the gut.

PMID- 16456025
TI  - Persistent cytomegalovirus-specific memory responses in the lung allograft and
      blood following primary infection in lung transplant recipients.
AB  - Primary CMV infection in lung transplant recipients (LTRs) is associated with
      increased mortality. We studied 22 donor CMV-positive, recipient-negative (D(+)R(
      )) LTRs for the development of posttransplant CMV-specific immunity. We found
      that 13 of 22 D(+)R(-) LTRs (59.1%) seroconverted (CMV IgG Ab(+)). Using pooled
      peptides of the immunodominant CMV Ags pp65 and IE1, we detected CMV-specific
      CD8(+)IFN-gamma(+) T cells in the PBMC of 90% of seroconverted individuals
      following primary infection by intracellular cytokine staining. In contrast, few
      seroconverters had detectable CMV-specific CD4(+)IFN-gamma(+) T cells during
      viral latency. However, the majority of IgG(+) LTRs demonstrated CMV-specific
      CD4(+) and CD8(+) T cell proliferative responses from PBMC, with CD4(+)IFN
      gamma(+) T cells detectable upon re-expansion. Examination of lung allograft
      mononuclear cells obtained by bronchoalveolar lavage revealed both CMV-specific
      CD4(+) and CD8(+)IFN-gamma(+) T cells, including patients from whom CD4(+)IFN
      gamma(+) T cells were simultaneously undetectable in the PBMC, suggesting
      differential effector memory populations between these compartments. Moreover,
      both responses in the PBMC and lung allograft were found to persist, despite
      substantial immunosuppression, long after primary infection. Clinical correlation
      in this cohort demonstrated that the acquisition of CMV immunity was associated
      with freedom from CMV disease (p < or = 0.009) and preservation of allograft
      function (p < or = 0.02) compared with those who failed to develop CMV immunity.
      Together, our data reveal immunologic heterogeneity in D(+)R(-) LTRs, with the
      development and persistence of primary CMV responses that may provide clinical
      benefit.

PMID- 16456026
TI  - Tolerance induction by transcutaneous immunization through ultraviolet-irradiated
      skin is transferable through CD4+CD25+ T regulatory cells and is dependent on
      host-derived IL-10.
AB  - UV radiation of the skin impairs immune responses to haptens and to tumor Ags.
      Transcutaneous immunization (TCI) is an effective method of inducing immune
      responses to protein and peptide Ag. We explore the effect of UV irradiation on
      TCI. The generation of Ag-specific CTL to OVA protein, but not class I MHC
      restricted OVA peptide, is inhibited by TCI through UV-irradiated skin.
      Consequently, the induction of protein contact hypersensitivity and in vivo Ag
      specific CTL activity following OVA protein immunization is prevented.
      Application of haptens to UV-exposed skin induces hapten-specific tolerance. We
      demonstrate that application of protein or class II MHC-restricted OVA peptide to
      UV-irradiated skin induces transferable Ag-specific tolerance. This tolerance is
      mediated by CD4(+)CD25(+) T regulatory (T(reg)) cells. These Ag-specific T(reg)
      cells inhibit the priming of CTL following protein immunization in the presence
      of CpG adjuvant. IL-10 deficiency is known to prevent hapten-specific tolerance
      induction. In this study, we demonstrate, using IL-10-deficient mice and adoptive
      T cell transfer, that IL-10 is required for the direct inhibition of CTL priming
      following immunization through UV-irradiated skin. However, IL-10 is not required
      for the induction of T(reg) cells through UV-irradiated skin as IL-10-deficient
      T(reg) cells are able to mediate tolerance. Rather, host-derived IL-10 is
      required for the function of UV-generated T(reg) cells. These experiments
      indicate that protein and peptide TCI through UV-irradiated skin may be used to
      induce robust Ag-specific tolerance to neo-Ags and that UV-induced T(reg) cells
      mediate their effects in part through the modulation of IL-10.

PMID- 16456027
TI  - Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire
      shrinkage predicting mortality and an increased number of dysfunctional
      cytomegalovirus-specific T cells in the very elderly.
AB  - The age-associated decrease in functionality of the human immune system is
      thought to have a negative impact on the capacity to provide protection against
      infection, in turn leading to increased incidence of mortality. In a previous
      longitudinal study of octogenarians, we identified an immune risk phenotype (IRP)
      in the very elderly defined by an inverted CD4/CD8 ratio, which was associated
      with increased mortality and persistent CMV infection. In this study, we analyzed
      the CD8 clonal composition of nonagenarians and middle-aged individuals. An
      increased number of CD8 T cell clones was observed in the nonagenarians, and was
      associated with CMV-seropositivity. Surprisingly, CMV-seropositive nonagenarians
      with the IRP had a significantly lower number of clones compared with non-IRP
      individuals. The decrease in clone numbers in IRP individuals was associated with
      shorter survival time. MHC/peptide multimer staining indicated that the frequency
      of CMV-specific T cells was higher in nonagenarians than in the middle-aged, but
      the ratio of functionally intact cells was significantly lower. The lowest ratio
      of functional CMV-specific T cells was found in an IRP individual. A thorough
      longitudinal analysis of the CMV-specific T cells in nonagenarians showed a
      stable pattern with respect to frequency, phenotype, and clonal composition. We
      hypothesize that the number of different CD8 T cell clonal expansions increases
      as the individual ages, possibly, as a compensatory mechanism to control latent
      infections, e.g., CMV, but eventually a point is reached where clonal exhaustion
      leads to shrinkage of the CD8 clonal repertoire, associated with decreased
      survival.

PMID- 16456028
TI  - B cells are crucial for determinant spreading of T cell autoimmunity among beta
      cell antigens in diabetes-prone nonobese diabetic mice.
AB  - The determinant spreading of T cell autoimmunity plays an important role in the
      pathogenesis of type 1 diabetes and in the protective mechanism of Ag-based
      immunotherapy in NOD mice. However, little is known about the role of APCs,
      particularly B cells, in the spreading of T cell autoimmunity. We studied
      determinant spreading in NOD/scid or Igmu(-/-) NOD mice reconstituted with NOD T
      and/or B cells and found that mice with mature B cells (TB NOD/scid and BMB Igmu(
      /-) NOD), but not mice that lacked mature B cells (T NOD/scid and BM Igmu(-/-)
      NOD), spontaneously developed Th1 autoimmunity, which spread sequentially among
      different beta cell Ags. Immunization of T NOD/scid and BM Igmu(-/-) NOD mice
      with a beta cell Ag could prime Ag-specific Th1 or Th2 responses, but those T
      cell responses did not spread to other beta cell Ags. In contrast, immunization
      of TB NOD/scid and BMB Igmu(-/-) NOD mice with a beta cell Ag in IFA induced Th2
      responses, which spread to other beta cell Ags. Furthermore, we found that while
      macrophages and dendritic cells could evoke memory and effector T cell responses
      in vitro, B cells significantly enhanced the detection of spontaneously primed
      and induced Th1 responses to beta cell Ags. Our data suggest that B cells, but
      not other APCs, mediate the spreading of T cell responses during the type 1
      diabetes process and following Ag-based immunotherapy. Conceivably, the
      modulation of the capacity of B cells to present Ag may provide new interventions
      for enhancing Ag-based immunotherapy and controlling autoimmune diseases.

PMID- 16456029
TI  - HIV-specific cytotoxic cell frequencies measured directly ex vivo by the Lysispot
      assay can be higher or lower than the frequencies of IFN-gamma-secreting cells:
      anti-HIV cytotoxicity is not generally impaired relative to other chronic virus
      responses.
AB  - CD8(+) T cells in HIV-infected patients are believed to contribute to the
      containment of the virus and the delay of disease progression. However, the
      frequencies of HIV-specific CD8(+) T cells, as measured by IFN-gamma secretion
      and tetramer binding, often do not correlate with a delay in disease progression
      during chronic infection. Using the Lysispot and ELISPOT assays, we measured the
      frequencies of cytotoxic and IFN-gamma-secreting T cells responding to
      overlapping peptides from Gag, Nef, Env, and Pol consensus HIV-1 clade B
      sequences. PBMC from the majority of HIV-infected subjects have significant
      frequencies of HIV-specific cells that killed targets within 5 h directly ex
      vivo. The relative frequencies of IFN-gamma-secreting and cytotoxic cells varied
      markedly between different HIV peptide pools within the same patient, and some T
      cells lysed targets without secreting IFN-gamma. These results indicate that
      measurement of IFN-gamma production alone may be insufficient to evaluate the
      breadth of the HIV-specific T cell response. Also, neither the CTL to IFN-gamma
      ratios nor the ex vivo CTL frequencies specific for different HIV proteins were
      consistently lower than responses specific for two other chronic viral
      infections, human CMV and EBV, within the same subjects. Thus ex vivo cytotoxic T
      cell frequencies do not provide evidence for a model of "preterminal
      differentiation" of HIV-specific CD8(+) T cells during chronic HIV infection.
      Analysis of the frequency of directly cytotoxic HIV-specific T cells may be of
      considerable value in the assessment of disease progression and the potential
      efficacy of HIV vaccines.

PMID- 16456030
TI  - Molecular dynamics simulations of sarcin-ricin rRNA motif.
AB  - Explicit solvent molecular dynamics (MD) simulations were carried out for sarcin
      ricin domain (SRD) motifs from 23S (Escherichia coli) and 28S (rat) rRNAs. The
      SRD motif consists of GAGA tetraloop, G-bulged cross-strand A-stack, flexible
      region and duplex part. Detailed analysis of the overall dynamics, base pairing,
      hydration, cation binding and other SRD features is presented. The SRD is
      surprisingly static in multiple 25 ns long simulations and lacks any non-local
      motions, with root mean square deviation (r.m.s.d.) values between averaged MD
      and high-resolution X-ray structures of 1-1.4 A. Modest dynamics is observed in
      the tetraloop, namely, rotation of adenine in its apex and subtle reversible
      shift of the tetraloop with respect to the adjacent base pair. The deformed
      flexible region in low-resolution rat X-ray structure is repaired by simulations.
      The simulations reveal few backbone flips, which do not affect positions of bases
      and do not indicate a force field imbalance. Non-Watson-Crick base pairs are
      rigid and mediated by long-residency water molecules while there are several
      modest cation-binding sites around SRD. In summary, SRD is an unusually stiff
      rRNA building block. Its intrinsic structural and dynamical signatures seen in
      simulations are strikingly distinct from other rRNA motifs such as Loop E and
      Kink-turns.

PMID- 16456031
TI  - HelF, a putative RNA helicase acts as a nuclear suppressor of RNAi but not
      antisense mediated gene silencing.
AB  - We have identified a putative RNA helicase from Dictyostelium that is closely
      related to drh-1, the 'dicer-related-helicase' from Caenorhabditis elegans and
      that also has significant similarity to proteins from vertebrates and plants.
      Green fluorescent protein (GFP)-tagged HelF protein was localized in speckles in
      the nucleus. Disruption of the helF gene resulted in a mutant morphology in late
      development. When transformed with RNAi constructs, HelF- cells displayed
      enhanced RNA interference on four tested genes. One gene that could not be
      knocked-down in the wild-type background was efficiently silenced in the mutant.
      Furthermore, the efficiency of silencing in the wild-type was dramatically
      improved when helF was disrupted in a secondary transformation. Silencing
      efficiency depended on transcription levels of hairpin RNA and the threshold was
      dramatically reduced in HelF- cells. However, the amount of siRNA did not depend
      on hairpin transcription. HelF is thus a natural nuclear suppressor of RNA
      interference. In contrast, no improvement of gene silencing was observed when
      mutant cells were challenged with corresponding antisense constructs. This
      indicates that RNAi and antisense have distinct requirements even though they may
      share parts of their pathways.

PMID- 16456032
TI  - Engineering a rare-cutting restriction enzyme: genetic screening and selection of
      NotI variants.
AB  - Restriction endonucleases (REases) with 8-base specificity are rare specimens in
      nature. NotI from Nocardia otitidis-caviarum (recognition sequence 5'-GCGGCCGC
      3') has been cloned, thus allowing for mutagenesis and screening for enzymes with
      altered 8-base recognition and cleavage activity. Variants possessing altered
      specificity have been isolated by the application of two genetic methods. In step
      1, variant E156K was isolated by its ability to induce DNA-damage in an indicator
      strain expressing M.EagI (to protect 5'-NCGGCCGN-3' sites). In step 2, the E156K
      allele was mutagenized with the objective of increasing enzyme activity towards
      the alternative substrate site: 5'-GCTGCCGC-3'. In this procedure, clones of
      interest were selected by their ability to eliminate a conditionally toxic
      substrate vector and induce the SOS response. Thus, specific DNA cleavage was
      linked to cell survival. The secondary substitutions M91V, F157C and V348M were
      each found to have a positive effect on specific activity when paired with E156K.
      For example, variant M91V/E156K cleaves 5'-GCTGCCGC-3' with a specific activity
      of 8.2 x 10(4) U/mg, a 32-fold increase over variant E156K. A comprehensive
      analysis indicates that the cleavage specificity of M91V/E156K is relaxed to a
      small set of 8 bp substrates while retaining activity towards the NotI sequence.

PMID- 16456033
TI  - Crystal structure determination and site-directed mutagenesis of the Pyrococcus
      abyssi aCBF5-aNOP10 complex reveal crucial roles of the C-terminal domains of
      both proteins in H/ACA sRNP activity.
AB  - In archaeal rRNAs, the isomerization of uridine into pseudouridine (Psi) is
      achieved by the H/ACA sRNPs and the minimal set of proteins required for RNA:Psi
      synthase activity is the aCBF5-aNOP10 protein pair. The crystal structure of the
      aCBF5-aNOP10 heterodimer from Pyrococcus abyssi was solved at 2.1 A resolution.
      In this structure, protein aNOP10 has an extended shape, with a zinc-binding
      motif at the N-terminus and an alpha-helix at the C-terminus. Both motifs contact
      the aCBF5 catalytic domain. Although less efficiently as does the full-length
      aNOP10, the aNOP10 C-terminal domain binds aCBF5 and stimulates the RNA-guided
      activity. We show that the C-terminal domain of aCBF5 (the PUA domain), which is
      wrapped by an N-terminal extension of aCBF5, plays a crucial role for aCBF5
      binding to the guide sRNA. Addition of this domain in trans partially complement
      particles assembled with an aCBF5DeltaPUA truncated protein. In the crystal
      structure, the aCBF5-aNOP10 complex forms two kinds of heterotetramers with
      parallel and perpendicular orientations of the aNOP10 terminal alpha-helices,
      respectively. By gel filtration assay, we showed that aNOP10 can dimerize in
      solution. As both residues Y41 and L48 were needed for dimerization, the
      dimerization likely takes place by interaction of parallel alpha-helices.

PMID- 16456035
TI  - Cellular senescence in aging primates.
AB  - The aging of organisms is characterized by a gradual functional decline of all
      organ systems. Mammalian somatic cells in culture display a limited proliferative
      life span, at the end of which they undergo an irreversible cell cycle arrest
      known as replicative senescence. Whether cellular senescence contributes to
      organismal aging has been controversial. We investigated telomere dysfunction, a
      recently discovered biomarker of cellular senescence, and found that the number
      of senescent fibroblasts increases exponentially in the skin of aging baboons,
      reaching >15% of all cells in very old individuals. In addition, the same cells
      contain activated ataxia-telangiectasia mutated kinase and heterochromatinized
      nuclei, confirming their senescent status.

PMID- 16456034
TI  - Haploinsufficiency of the Mus81-Eme1 endonuclease activates the intra-S-phase and
      G2/M checkpoints and promotes rereplication in human cells.
AB  - The Mus81-Eme1 complex is a structure-specific endonuclease that preferentially
      cleaves nicked Holliday junctions, 3'-flap structures and aberrant replication
      fork structures. Mus81-/- mice have been shown to exhibit spontaneous chromosomal
      aberrations and, in one of two models, a predisposition to cancers. The molecular
      mechanisms underlying its role in chromosome integrity, however, are largely
      unknown. To clarify the role of Mus81 in human cells, we deleted the gene in the
      human colon cancer cell line HCT116 by gene targeting. Here we demonstrate that
      Mus81 confers resistance to DNA crosslinking agents and slight resistance to
      other DNA-damaging agents. Mus81 deficiency spontaneously promotes chromosome
      damage such as breaks and activates the intra-S-phase checkpoint through the ATM
      Chk1/Chk2 pathways. Furthermore, Mus81 deficiency activates the G2/M checkpoint
      through the ATM-Chk2 pathway and promotes DNA rereplication. Increased
      rereplication is reversed by the ectopic expression of Cdk1. Haploinsufficiency
      of Mus81 or Eme1 also causes similar phenotypes. These findings suggest that a
      complex network of the checkpoint pathways that respond to DNA double-strand
      breaks may participate in some of the phenotypes associated with Mus81 or Eme1
      deficiency.

PMID- 16456036
TI  - Late Precambrian oxygenation; inception of the clay mineral factory.
AB  - An enigmatic stepwise increase in oxygen in the late Precambrian is widely
      considered a prerequisite for the expansion of animal life. Accumulation of
      oxygen requires organic matter burial in sediments, which is largely controlled
      by the sheltering or preservational effects of detrital clay minerals in modern
      marine continental margin depocenters. Here, we show mineralogical and
      geochemical evidence for an increase in clay mineral deposition in the
      Neoproterozoic that immediately predated the first metazoans. Today most clay
      minerals originate in biologically active soils, so initial expansion of a
      primitive land biota would greatly enhance production of pedogenic clay minerals
      (the "clay mineral factory"), leading to increased marine burial of organic
      carbon via mineral surface preservation.

PMID- 16456037
TI  - Exposed water ice deposits on the surface of comet 9P/Tempel 1.
AB  - We report the direct detection of solid water ice deposits exposed on the surface
      of comet 9P/Tempel 1, as observed by the Deep Impact mission. Three anomalously
      colored areas are shown to include water ice on the basis of their near-infrared
      spectra, which include diagnostic water ice absorptions at wavelengths of 1.5 and
      2.0 micrometers. These absorptions are well modeled as a mixture of nearby non
      ice regions and 3 to 6% water ice particles 10 to 50 micrometers in diameter.
      These particle sizes are larger than those ejected during the impact experiment,
      which suggests that the surface deposits are loose aggregates. The total area of
      exposed water ice is substantially less than that required to support the
      observed ambient outgassing from the comet, which likely has additional source
      regions below the surface.

PMID- 16456038
TI  - MOSFET-Embedded microcantilevers for measuring deflection in biomolecular
      sensors.
AB  - A promising approach for detecting biomolecules follows their binding to
      immobilized probe molecules on microfabricated cantilevers; binding causes
      surface stresses that bend the cantilever. We measured this deflection, which is
      on the order of tens of nanometers, by embedding a metal-oxide semiconductor
      field-effect transistor (MOSFET) into the base of the cantilever and recording
      decreases in drain current with deflections as small as 5 nanometers. The gate
      region of the MOSFET responds to surface stresses and thus is embedded in silicon
      nitride so as to avoid direct contact with the sample solution. This approach,
      which offers low noise, high sensitivity, and direct readout, was used to detect
      specific binding events with biotin and antibodies.

PMID- 16456040
TI  - Advancing the frontiers.

PMID- 16456039
TI  - The global impact of scaling up HIV/AIDS prevention programs in low- and middle
      income countries.
AB  - A strong, global commitment to expanded prevention programs targeted at sexual
      transmission and transmission among injecting drug users, started now, could
      avert 28 million new HIV infections between 2005 and 2015. This figure is more
      than half of the new infections that might otherwise occur during that period in
      125 low- and middle-income countries. Although preventing these new infections
      would require investing about U.S.$122 billion over this period, it would reduce
      future needs for treatment and care. Our analysis suggests that it will cost
      about U.S.$3900 to prevent each new infection, but that this will produce a
      savings of U.S.$4700 in forgone treatment and care costs. Thus, greater spending
      on prevention now would not only prevent more than half the new infections that
      would occur from 2005 to 2015 but would actually produce a net financial saving
      as future costs for treatment and care are averted.

PMID- 16456041
TI  - Science education. Strategies evolve as candidates prepare for Kansas board
      races.

PMID- 16456042
TI  - Planetary science. New Hubble image cuts the "10th planet" down to size.

PMID- 16456043
TI  - Evolution. Hidden genetic variation yields caterpillar of a different color.

PMID- 16456044
TI  - Infectious diseases. Tackling neglected diseases could offer more bang for the
      buck.

PMID- 16456045
TI  - Global warming. Climate change demands action, says U.K. report.

PMID- 16456046
TI  - Biomedical research policy. NIH lends a hand to postdocs seeking to become
      independent researchers.

PMID- 16456047
TI  - Theoretical physics. Ring around a quasar may deflate quantum foam after all.

PMID- 16456048
TI  - U.S. innovation. Bandwagon builds for energy research.

PMID- 16456049
TI  - Scientific conduct. Panel discredits findings of Tokyo university team.

PMID- 16456050
TI  - Neuroscience. A timely debate about the brain.

PMID- 16456053
TI  - American Astronomical Society meeting. Laser points to bright new era for ground
      based astronomy.

PMID- 16456051
TI  - Arata Kochi profile. Fighting words from WHO's new malaria chief.

PMID- 16456052
TI  - Biomedical engineering. Spending itself out of existence, Whitaker brings a field
      to life.

PMID- 16456054
TI  - American Astronomical Society meeting. Pulsar sets a dizzying standard.

PMID- 16456055
TI  - American Astronomical Society meeting. Pesky companions warp the Milky Way.

PMID- 16456056
TI  - American Astronomical Society meeting. Snapshots from the meeting.

PMID- 16456062
TI  - Reactions to the Hwang scandal.

PMID- 16456063
TI  - Questions about forensic science.

PMID- 16456064
TI  - Comment on "Neutral ecological theory reveals isolation and rapid speciation in a
      biodiversity hot spot".
AB  - Latimer et al. (Reports, 9 September 2005, p. 1722) used an approximate
      likelihood function to estimate parameters of Hubbell's neutral model of
      biodiversity. Reanalysis with the exact likelihood not only yields different
      estimates but also shows that two similar likelihood maxima for very different
      parameter combinations can occur. This reveals a limitation of using species
      abundance data to gain insight into speciation and dispersal.

PMID- 16456065
TI  - Research conduct. Lessons of the stem cell scandal.

PMID- 16456066
TI  - Public health. Community studies for vaccinating schoolchildren against
      influenza.

PMID- 16456068
TI  - Astronomy. Big fields on small stars.

PMID- 16456067
TI  - Neuroscience. What's in a face?

PMID- 16456069
TI  - Chemistry. Better asymmetric reactions.

PMID- 16456070
TI  - Epidemiology. Understanding HIV epidemic trends in Africa.

PMID- 16456071
TI  - Toxic potential of materials at the nanolevel.
AB  - Nanomaterials are engineered structures with at least one dimension of 100
      nanometers or less. These materials are increasingly being used for commercial
      purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics,
      microelectronics, and drug carriers. Materials in this size range may approach
      the length scale at which some specific physical or chemical interactions with
      their environment can occur. As a result, their properties differ substantially
      from those bulk materials of the same composition, allowing them to perform
      exceptional feats of conductivity, reactivity, and optical sensitivity. Possible
      undesirable results of these capabilities are harmful interactions with
      biological systems and the environment, with the potential to generate toxicity.
      The establishment of principles and test procedures to ensure safe manufacture
      and use of nanomaterials in the marketplace is urgently required and achievable.

PMID- 16456072
TI  - Effective seed dispersal across a fragmented landscape.
AB  - The role of seed dispersal in maintaining genetic connectivity among forest
      fragments has largely been ignored because gene flow by pollen is expected to
      predominate. By using genealogical reconstruction, we investigated gene flow
      after establishment of seeds in a wind-pollinated, wind-dispersed tree. Our data
      show that seed dispersal is the main vector of gene flow among remnants and that
      long-distance dispersal is common across a chronically fragmented landscape. The
      relative importance of seed-mediated gene flow may have been underemphasized in
      other fragmented systems, and diagnosing the response of forest trees to current
      anthropogenic disturbances requires the assessment of phenomena after
      establishment.

PMID- 16456073
TI  - The large-scale axisymmetric magnetic topology of a very-low-mass fully
      convective star.
AB  - Understanding how cool stars produce magnetic fields within their interiors is
      crucial for predicting the impact of such fields, such as the activity cycle of
      the Sun. In this respect, studying fully convective stars enables us to
      investigate the role of convective zones in magnetic field generation. We
      produced a magnetic map of a rapidly rotating, very-low-mass, fully convective
      dwarf through tomographic imaging from time series of spectropolarimetric data.
      Our results, which demonstrate that fully convective stars are able to trigger
      axisymmetric large-scale poloidal fields without differential rotation, challenge
      existing theoretical models of field generation in cool stars.

PMID- 16456074
TI  - Plasticization-enhanced hydrogen purification using polymeric membranes.
AB  - Polymer membranes are attractive for molecular-scale separations such as hydrogen
      purification because of inherently low energy requirements. However, membrane
      materials with outstanding hydrogen separation performance in feed streams
      containing high-pressure carbon dioxide and impurities such as hydrogen sulfide
      and water are not available. We report highly permeable, reverse-selective
      membrane materials for hydrogen purification, as exemplified by molecularly
      engineered, highly branched, cross-linked poly(ethylene oxide). In contrast to
      the performance of conventional materials, we demonstrate that plasticization can
      be harnessed to improve separation performance.

PMID- 16456075
TI  - Plastic deformation of MgGeO3 post-perovskite at lower mantle pressures.
AB  - Polycrystalline MgGeO3 post-perovskite was plastically deformed in the diamond
      anvil cell between 104 and 130 gigapascals confining pressure and ambient
      temperature. In contrast with phenomenological considerations suggesting (010) as
      a slip plane, lattice planes near (100) became aligned perpendicular to the
      compression direction, suggesting that slip on (100) or (110) dominated plastic
      deformation. With the assumption that silicate post-perovskite behaves similarly
      at lower mantle conditions, a numerical model of seismic anisotropy in the D''
      region implies a maximum contribution of post-perovskite to shear wave splitting
      of 3.7% with an oblique polarization.

PMID- 16456076
TI  - Natural and experimental evidence of melt lubrication of faults during
      earthquakes.
AB  - Melt produced by friction during earthquakes may act either as a coseismic fault
      lubricant or as a viscous brake. Here we estimate the dynamic shear resistance
      (tau(f)) in the presence of friction-induced melts from both exhumed faults and
      high-velocity (1.28 meters per second) frictional experiments. Exhumed faults
      within granitoids (tonalites) indicate low tau(f) at 10 kilometers in depth.
      Friction experiments on tonalite samples show that tau(f) depends weakly on
      normal stress. Extrapolation of experimental data yields tau(f) values consistent
      with the field estimates and well below the Byerlee strength. We conclude that
      friction-induced melts can lubricate faults at intermediate crustal depths.

PMID- 16456077
TI  - Evolution of a polyphenism by genetic accommodation.
AB  - Polyphenisms are adaptations in which a genome is associated with discrete
      alternative phenotypes in different environments. Little is known about the
      mechanism by which polyphenisms originate. We show that a mutation in the
      juvenile hormone-regulatory pathway in Manduca sexta enables heat stress to
      reveal a hidden reaction norm of larval coloration. Selection for increased color
      change in response to heat stress resulted in the evolution of a larval color
      polyphenism and a corresponding change in hormonal titers through genetic
      accommodation. Evidently, mechanisms that regulate developmental hormones can
      mask genetic variation and act as evolutionary capacitors, facilitating the
      origin of novel adaptive phenotypes.

PMID- 16456078
TI  - Resolving the motional modes that code for RNA adaptation.
AB  - Using a domain elongation strategy, we decoupled internal motions in RNA from
      overall rotational diffusion. This allowed us to site-specifically resolve a
      manifold of motional modes in two regulatory RNAs from HIV-1 with the use of
      nuclear magnetic resonance spin relaxation methods. Base and sugar librations
      vary on a picosecond time scale and occur within helical domains that move
      collectively at diffusion-limited nanosecond time scales. Pivot points are short,
      functionally important, and highly mobile internal loops. These spontaneous
      changes in RNA conformation correlate quantitatively with those that follow
      adaptive recognition of diverse targets. Thus, ligands may stabilize existing RNA
      conformations rather than inducing new ones.

PMID- 16456079
TI  - Structure of human urokinase plasminogen activator in complex with its receptor.
AB  - The urokinase plasminogen activator binds to its cellular receptor with high
      affinity and initiates signaling cascades that are implicated in pathological
      processes including tumor growth, metastasis, and inflammation. We report the
      crystal structure at 1.9 angstroms of the urokinase receptor complexed with the
      urokinase amino-terminal fragment and an antibody against the receptor. The three
      domains of urokinase receptor form a concave shape with a central cone-shaped
      cavity where the urokinase fragment inserts. The structure provides insight into
      the flexibility of the urokinase receptor that enables its interaction with a
      wide variety of ligands and a basis for the design of urokinase-urokinase
      receptor antagonists.

PMID- 16456080
TI  - Fish population and behavior revealed by instantaneous continental shelf-scale
      imaging.
AB  - Until now, continental shelf environments have been monitored with highly
      localized line-transect methods from slow-moving research vessels. These methods
      significantly undersample fish populations in time and space, leaving an
      incomplete and ambiguous record of abundance and behavior. We show that fish
      populations in continental shelf environments can be instantaneously imaged over
      thousands of square kilometers and continuously monitored by a remote sensing
      technique in which the ocean acts as an acoustic waveguide. The technique has
      revealed the instantaneous horizontal structural characteristics and volatile
      short-term behavior of very large fish shoals, containing tens of millions of
      fish and stretching for many kilometers.

PMID- 16456081
TI  - HIV decline associated with behavior change in eastern Zimbabwe.
AB  - Few sub-Saharan African countries have witnessed declines in HIV prevalence, and
      only Uganda has compelling evidence for a decline founded on sexual behavior
      change. We report a decline in HIV prevalence in eastern Zimbabwe between 1998
      and 2003 associated with sexual behavior change in four distinct socioeconomic
      strata. HIV prevalence fell most steeply at young ages-by 23 and 49%,
      respectively, among men aged 17 to 29 years and women aged 15 to 24 years-and in
      more educated groups. Sexually experienced men and women reported reductions in
      casual sex of 49 and 22%, respectively, whereas recent cohorts reported delayed
      sexual debut. Selective AIDS-induced mortality contributed to the decline in HIV
      prevalence.

PMID- 16456082
TI  - Rats smell in stereo.
AB  - It has been hypothesized that rats and other mammals can use stereo cues to
      localize odor sources, but there is limited behavioral evidence to support this
      hypothesis. We found that rats trained on an odor-localization task can localize
      odors accurately in one or two sniffs. Bilateral sampling was essential for
      accurate odor localization, with internasal intensity and timing differences as
      directional cues. If the stimulus arrived at the correct point of the respiration
      cycle, internasal timing differences as short as 50 milliseconds sufficed.
      Neuronal recordings show that bulbar neurons responded differentially to stimuli
      from the left and stimuli from the right.

PMID- 16456083
TI  - A cortical region consisting entirely of face-selective cells.
AB  - Face perception is a skill crucial to primates. In both humans and macaque
      monkeys, functional magnetic resonance imaging (fMRI) reveals a system of
      cortical regions that show increased blood flow when the subject views images of
      faces, compared with images of objects. However, the stimulus selectivity of
      single neurons within these fMRI-identified regions has not been studied. We used
      fMRI to identify and target the largest face-selective region in two macaques for
      single-unit recording. Almost all (97%) of the visually responsive neurons in
      this region were strongly face selective, indicating that a dedicated cortical
      area exists to support face processing in the macaque.

PMID- 16456084
TI  - D-propranolol attenuates lysosomal iron accumulation and oxidative injury in
      endothelial cells.
AB  - The influence of selected beta-receptor blockers on iron overload and oxidative
      stress in endothelial cells (ECs) was assessed. Confluent bovine ECs were loaded
      with iron dextran (15 muM) for 24 h and then exposed to dihydroxyfumarate (DHF),
      a source of reactive oxygen species, for up to 2 h. Intracellular oxidant
      formation, monitored by fluorescence of 2',7'-dichlorofluorescin (DCF; 30
      microM), increased and peaked at 30 min; total glutathione decreased by 52 +/- 5%
      (p < 0.01) at 60 min. When the ECs were pretreated 30 min before iron loading
      with 1.25 to 10 microM d-propranolol, glutathione losses were attenuated 15 to
      80%, with EC(50) = 3.1 microM. d-Propranolol partially inhibited the DCF
      intensity increase, but atenolol up to 10 microM was ineffective. At 2 h, caspase
      3 activity was elevated 3.2 +/- 0.3-fold (p < 0.01) in the iron-loaded and DHF
      treated ECs, and cell survival, determined 24 h later, decreased 47 +/- 6% (p <
      0.01). Ten micromoles of d-propranolol suppressed the caspase 3 activation by 63%
      (p < 0.05) and preserved cell survival back to 88% of control (p < 0.01). In
      separate experiments, 24-h iron loading resulted in a 3.6 +/- 0.8-fold increase
      in total EC iron determined by atomic absorption spectroscopy; d-propranolol at 5
      microM reduced this increase to 1.5 +/- 0.4-fold (p < 0.01) of controls.
      Microscopic observation by Perls' staining revealed that the excessive iron
      accumulated in vesicular endosomal/lysosomal structures, which were substantially
      diminished by d-propranolol. We previously showed that propranolol could readily
      concentrate into the lysosomes and raise the intralysosomal pH; it is suggested
      that the lysosomotropic properties of d-propranolol retarded the EC iron
      accumulation and thereby conferred the protective effects against iron load
      mediated cytotoxicity.

PMID- 16456085
TI  - Choice between heroin and food in nondependent and heroin-dependent rhesus
      monkeys: effects of naloxone, buprenorphine, and methadone.
AB  - Several medications are approved for treatment of opiate abuse, but determinants
      of their clinical effectiveness are not completely understood. States of opiate
      dependence or withdrawal may constitute one important set of determinants. To
      test this hypothesis, the effects of naloxone, buprenorphine, and methadone were
      assessed on choice between heroin and food in nondependent rhesus monkeys and in
      heroin-dependent monkeys undergoing withdrawal. A choice procedure was used to
      permit dissociation of medication effects on the relative reinforcing properties
      of heroin from nonselective effects on response rates. In nondependent monkeys,
      increasing unit doses of heroin (0-0.1 mg/kg/injection) maintained dose-dependent
      increases in heroin choice. Chronic 5-day treatment with naloxone (0.01-0.32
      mg/kg/h) or buprenorphine (0.01-0.1 mg/kg/day) produced dose-dependent rightward
      shifts in heroin choice dose-effect curves, whereas chronic methadone (0.1-0.56
      mg/kg/h) had little effect on heroin choice up to doses that suppressed
      responding. In heroin-dependent monkeys, opiate withdrawal produced overt
      abstinence signs as well as increases in heroin choice, manifested as leftward
      shifts in heroin choice dose-effect curves. The withdrawal-associated increases
      in heroin choice suggest that opiate withdrawal increased the relative
      reinforcing efficacy of heroin in comparison with food, an effect that may be
      related to relapse in humans. Methadone prevented withdrawal-associated increases
      in heroin choice, whereas buprenorphine was less effective. These findings
      suggest that agonist medications such as methadone may derive their clinical
      utility from their ability to attenuate withdrawal-associated increases in opiate
      reinforcement. Moreover, this procedure may be useful for exploring mechanisms
      underlying withdrawal-associated increases in opiate reinforcement and for
      testing candidate medications.

PMID- 16456087
TI  - Adamantane resistance among influenza A viruses isolated early during the 2005
      2006 influenza season in the United States.
AB  - CONTEXT: The adamantanes, amantadine and rimantadine, have been used as first
      choice antiviral drugs against community outbreaks of influenza A viruses for
      many years. Rates of viruses resistant to these drugs have been increasing
      globally. Rapid surveillance for the emergence and spread of resistant viruses
      has become critical for appropriate treatment of patients. OBJECTIVE: To
      investigate the frequency of adamantane-resistant influenza A viruses circulating
      in the United States during the initial months of the 2005-2006 influenza season.
      DESIGN AND SETTING: Influenza isolates collected from 26 states from October 1
      through December 31, 2005, and submitted to the US Centers for Disease Control
      and Prevention were tested for drug resistance as part of ongoing surveillance.
      Isolates were submitted from World Health Organization collaborating laboratories
      and National Respiratory and Enteric Virus Surveillance System laboratories. MAIN
      OUTCOME MEASURES: Using pyrosequencing and confirmatory assays, we identified
      viruses containing mutations within the M2 gene that are known to confer
      resistance to both amantadine and rimantadine. RESULTS: A total of 209 influenza
      A(H3N2) viruses isolated from patients in 26 states were screened, of which 193
      (92.3%) contained a change at amino acid 31 (serine to asparagine [S31N]) in the
      M2 gene known to be correlated with adamantane resistance. Two of 8 influenza
      A(H1N1) viruses contained the same mutation. Drug-resistant viruses were
      distributed across the United States. CONCLUSIONS: The high proportion of
      influenza A viruses currently circulating in the United States demonstrating
      adamantane resistance highlights the clinical importance of rapid surveillance
      for antiviral resistance. Our results indicate that these drugs should not be
      used for the treatment or prophylaxis of influenza in the United States until
      susceptibility to adamantanes has been reestablished among circulating influenza
      A isolates.

PMID- 16456088
TI  - Thrombomodulin gene polymorphisms and haplotypes and the risk of cardiovascular
      events: a prospective follow-up study.
AB  - BACKGROUND: Thrombomodulin is an anticoagulant expressed during endothelial
      activation and damage. To address the potential role of allelic variants of
      thrombomodulin gene in the pathogenesis of cardiovascular diseases, we analyzed
      in a prospective follow-up study 8 single-nucleotide polymorphisms (SNPs) across
      the thrombomodulin locus, covering all common (>5%) haplotypes. METHODS AND
      RESULTS: Two separate, stratified random samples of men and women 25 to 74 years
      of age were examined in Finland in 1992 and 1997. The total sample size was 14
      140 individuals, with 7 (1997 cohort) to 10 (1992 cohort) years of follow-up.
      Altogether, 662 individuals had a history of cardiovascular events already at
      baseline. During the follow-up, 401 incident coronary events and 148 incident
      ischemic strokes were observed. The alleles and common haplotypes of 8 SNPs were
      tested in Cox proportional hazards models using incident coronary events,
      incident ischemic strokes, and total mortality as end points. None of the SNPs or
      major SNP haplotypes showed consistent association with the end points analyzed
      in the combined data. CONCLUSIONS: Results from this prospective, population
      based study suggest that common allelic variants of the thrombomodulin gene may
      not significantly contribute to the risk of cardiovascular events at the
      population level.

PMID- 16456089
TI  - Macrophage ATP-binding cassette transporter A1 overexpression inhibits
      atherosclerotic lesion progression in low-density lipoprotein receptor knockout
      mice.
AB  - BACKGROUND: ATP-binding cassette transporter A1 (ABCA1) is a key regulator of
      cellular cholesterol and phospholipid transport. Previously, we have shown that
      inactivation of macrophage ABCA1 induces atherosclerosis in low-density
      lipoprotein receptor knockout (LDLr-/-) mice. However, the possibly beneficial
      effects of specific upregulation of macrophage ABCA1 on atherogenesis are still
      unknown. METHODS AND RESULTS: Chimeras that specifically overexpress ABCA1 in
      macrophages were generated by transplantation of bone marrow from human ABCA1
      bacterial artificial chromosome (BAC) transgenic mice into LDLr-/- mice.
      Peritoneal macrophages isolated from the ABCA1 BAC --> LDLr-/- chimeras exhibited
      a 60% (P=0.0006) increase in cholesterol efflux to apolipoprotein AI. To induce
      atherosclerosis, the mice were fed a Western-type diet containing 0.25%
      cholesterol and 15% fat for 9, 12, and 15 weeks, allowing analysis of effects on
      initial lesion development as well as advanced lesions. No significant effect of
      macrophage ABCA1 overexpression was observed on atherosclerotic lesion size after
      9 weeks on the Western-type diet (245+/-36x10(3) microm2 in ABCA1 BAC --> LDLr-/-
      mice versus 210+/-20x10(3) microm2 in controls). However, after 12 weeks, the
      mean atherosclerotic lesion area in ABCA1 BAC --> LDLr-/- mice remained only
      164+/-15x10(3) microm2 (P=0.0008) compared with 513+/-56x10(3) microm2 in
      controls (3.1-fold lower). Also, after 15 weeks on the diet, lesions in mice
      transplanted with ABCA1 overexpressing bone marrow were still 1.6-fold smaller
      (393+/-27x10(3) microm2 compared with 640+/-59x10(3) microm2 in control
      transplanted mice; P=0.0015). CONCLUSIONS: ABCA1 upregulation in macrophages
      inhibits the progression of atherosclerotic lesions.

PMID- 16456090
TI  - Comparison of circulating adiponectin and proinflammatory markers regarding their
      association with metabolic syndrome in Japanese men.
AB  - BACKGROUND: Anti-inflammatory and proinflammatory molecules purportedly play an
      important role in developing metabolic syndrome (MetS). However, little is known
      as to the relative importance of these molecules in the association with MetS.
      METHODS AND RESULTS: We studied 624 middle-aged Japanese men without medical
      history of cardiovascular disease or cancer and investigated the associations of
      circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C
      reactive protein (CRP), and adiponectin with MetS. We used the respective
      definitions proposed by the National Cholesterol Education Program Adult
      Treatment Panel III (ATP-III), the International Diabetes Federation, and the
      Japanese Society of Internal Medicine. Decreased serum adiponectin was observed
      in those with any of the ATP-III-MetS components, whereas this was not the case
      with increased TNF-alpha, IL-6, or CRP. Adiponectin and CRP levels linearly
      deteriorated with an increasing number of ATP-III-MetS components (trend P<0.001,
      respectively). Significantly higher CRP and lower adiponectin levels were
      observed in those who met any MetS criteria, whereas increased TNF-alpha was
      observed in only those with ATP-III-MetS. Finally, odds ratios (ORs) for MetS
      prevalence of a 1-SD increase/decrease in log-transformed 4 markers were
      calculated with multivariate logistic regression analyses. Consequently,
      decreased adiponectin was associated most strongly with ATP-III-MetS
      (adiponectin: OR, 1.90 [95% CI, 1.44 to 2.51]; P<0.001; CRP: OR, 1.33 [95% CI,
      1.01 to 1.74]; P=0.03; TNF-alpha: OR, 1.25 [95% CI, 0.94 to 1.67]; P=0.12; and IL
      6: OR, 0.87 [95% CI, 0.63 to 1.19]; P=0.37). This result was not altered by using
      the other 2 criteria. CONCLUSIONS: The present results raise the possibility that
      decreased serum adiponectin might be fundamentally involved in the development of
      MetS.

PMID- 16456091
TI  - Molecular signatures determining coronary artery and saphenous vein smooth muscle
      cell phenotypes: distinct responses to stimuli.
AB  - OBJECTIVE: Phenotypic differences between vascular smooth muscle cell (VSMC)
      subtypes lead to diverse pathological processes including atherosclerosis,
      postangioplasty restenosis and vein graft disease. To better understand the
      molecular mechanisms underlying functional differences among distinct SMC
      subtypes, we compared gene expression profiles and functional responses to
      oxidized low-density lipoprotein (OxLDL) and platelet-derived growth factor
      (PDGF) between cultured SMCs from human coronary artery (CASM) and saphenous vein
      (SVSM). METHODS AND RESULTS: OxLDL and PDGF elicited markedly different
      functional responses and expression profiles between the 2 SMC subtypes. In CASM,
      OxLDL inhibited cell proliferation and migration and modified gene expression of
      chemokines (CXCL10, CXCL11 and CXCL12), proinflammatory cytokines (IL-1, IL-6,
      and IL-18), insulin-like growth factor binding proteins (IGFBPs), and both
      endothelial and smooth muscle marker genes. In SVSM, OxLDL promoted proliferation
      partially via IGF1 signaling, activated NF-kappaB and phosphatidylinositol
      signaling pathways, and upregulated prostaglandin (PG) receptors and synthases.
      In untreated cells, alpha-chemokines, proinflammatory cytokines, and genes
      associated with apoptosis, inflammation, and lipid biosynthesis were higher in
      CASM, whereas some beta-chemokines, metalloproteinase inhibitors, and IGFBPs were
      higher in SVSM. Interestingly, the basal expression levels of these genes seemed
      closely related to their responses to OxLDL and PDGF. In summary, our results
      suggest dramatic differences in gene expression patterns and functional responses
      to OxLDL and PDGF between venous and arterial SMCs, with venous SMCs having
      stronger proliferative/migratory responses to stimuli but also higher expression
      of atheroprotective genes at baseline. CONCLUSIONS: These results reveal
      molecular signatures that define the distinct phenotypes characteristics of
      coronary artery and saphenous vein SMC subtypes.

PMID- 16456092
TI  - Endothelial NO synthase deficiency promotes smooth muscle progenitor cells in
      association with upregulation of stromal cell-derived factor-1alpha in a mouse
      model of carotid artery ligation.
AB  - BACKGROUND: Endothelial NO deficiency (endothelial NO synthase [eNOS]-knockout
      [KO]) enhanced smooth muscle cell (SMC)-rich neointimal lesion formation in a
      mouse model of carotid artery ligation (CAL). Recent evidence indicated that
      stromal cell-derived factor-1alpha (SDF-1alpha)-mediated recruitment of
      circulating SMC progenitor cells substantially contributed to the SMC-rich
      neointimal hyperplasia induced by vascular injury. The goal of this study was to
      investigate the effects of eNOS deficiency on the expression of SDF-1alpha and
      mobilization of circulating SMC progenitor cells in CAL model. METHODS AND
      RESULTS: Two- to 3-month-old C57BL/6J wild-type (WT) and eNOS-KO mice were
      evaluated 1, 2, or 4 weeks after CAL. CAL-induced expression of SDF-1alpha, as
      detected by immunohistochemical staining and further quantified by ELISA in the
      ligated carotid arteries, was moderate and transient with a peak at 1 week in WT
      mice. SDF-1alpha expression was significantly higher at 1 week and persisted
      through 2 weeks in eNOS-KO mice. CAL was associated with increased circulating
      stem cell antigen-1(+) (Sca-1(+))/c-Kit(-)/Lin- cells (interpreted as SMC
      progenitor cells), which peaked at 1 week in WT mice. This effect was also
      significantly greater and longer-lasting in eNOS-KO than WT mice. The number of
      circulating Sca-1(+)/c-Kit(-)/Lin- cells was positively correlated with the
      expression of SDF-1alpha but not vascular endothelial growth factor in the
      ligated carotid arteries. Furthermore, immunostaining showed abundant Sca-1
      positive cells in the adventitia of the 1-week ligated carotid arteries from eNOS
      KO mice but not in WT mice. We also determined that eNOS deficiency enhanced CAL
      induced intimal cell proliferation in the ligated arteries as detected by
      proliferating cell nuclear antigen staining but did not induce cell apoptosis as
      detected by staining for active caspase-3. CONCLUSIONS: Our results indicate that
      eNOS deficiency exacerbates CAL-induced expression of SDF-1alpha and its receptor
      CXCR4. This is correlated with an increase in Sca-1(+) cells in peripheral blood
      and adventitia, which may contribute to vascular remodeling and SMC-rich
      neointimal lesion formation. This suggests that constitutive eNOS inhibits SDF
      1alpha expression and provides an important vasculoprotective mechanism for
      intact endothelium to limit SMC proliferation and recruitment in response to
      vascular injury.

PMID- 16456093
TI  - Peroxisome proliferator-activated receptor-alpha,gamma-agonist improves insulin
      sensitivity and prevents loss of left ventricular function in obese dyslipidemic
      mice.
AB  - OBJECTIVE: We investigated the effect of a dual peroxisome proliferator-activated
      receptor (PPAR)alpha,gamma-agonist on atherosclerosis and cardiac function in
      mice with combined leptin and low-density lipoprotein receptor deficiency (DKO).
      In these mice, obesity, diabetes, and hyperlipidemia are associated with
      accelerated atherosclerosis and loss of cardiac function. METHODS AND RESULTS: We
      treated 12-week-old DKO mice with the PPARalpha,gamma-agonist (S)-3-(4-(2
      carbazol-9-yl-ethoxy) phenyl-2-ethoxy-propionic-acid) for 12 weeks. The agonist
      lowered free fatty acids with 42% and increased insulin sensitivity with 76%. It
      had no effect on plasma cholesterol and triglycerides. RT-PCR analysis showed
      that the agonist increased the expression of fatty acid transport protein-4,
      fatty acid binding protein-4, glucose transporter-4, hormone-sensitive lipase,
      and adiponectin in white adipose tissue that was associated with the increase in
      insulin sensitivity. At 24 weeks, the shortening fraction (SF) of placebo DKO
      mice was 30% lower than that of C57BL6 mice. The PPAR agonist increased PPARgamma
      but not PPARalpha expression in the heart and prevented loss of left ventricular
      function. Adiponectin correlated positively with PPARgamma in the heart and with
      SF. The agonist had no effect on atherosclerosis in the aortic arch of DKO mice.
      CONCLUSIONS: The dual PPARalpha,gamma-agonist improved insulin sensitivity
      without affecting cholesterol and triglycerides. This was associated with
      induction of PPARgamma in the heart and prevention of loss of left ventricle
      function.

PMID- 16456094
TI  - Urokinase plasminogen activator stimulates vascular smooth muscle cell
      proliferation via redox-dependent pathways.
AB  - OBJECTIVE: We showed previously that increased urokinase plasminogen activator
      (uPA) expression contributes to vascular smooth muscle cell (VSMC) proliferation
      and neointima formation after injury. Proliferation of cultured rat aortic VSMCs
      induced by uPA was inhibited by the antioxidant ebselen. Because increases in
      VSMC reactive oxygen species (ROS) contribute to VSMC proliferation, we
      hypothesized that uPA increases ROS generation by regulating expression or
      activity of cellular oxidases. METHODS AND RESULTS: uPA stimulated ROS production
      to levels equivalent to angiotensin II as measured by electron spin resonance and
      fluorescent redox indicators (dichlorofluorescein diacetate, lucigenin, and
      hydroethidine). The increase in ROS was biphasic, with the first peak at 30
      minutes and the second peak at 4 hours. uPA increased expression of the NAD(P)H
      oxidases Nox1 and Nox4 as measured by RT-PCR and Western blot analysis. Knockdown
      of Nox1 and Nox4 expression with small interfering RNA showed that both isoforms
      (Nox1>Nox4) contributed significantly to uPA-stimulated ROS production and VSMC
      proliferation. Transfection of VSMCs with uPA cDNA to increase endogenous uPA
      expression enhanced ROS production dramatically, suggesting that autocrine uPA
      production may be an important mechanism for uPA-mediated VSMC events.
      CONCLUSIONS: These data show that uPA is an autocrine VSMC growth factor that
      increases ROS generated by both Nox1 and Nox4 oxidases.

PMID- 16456095
TI  - Effect of modified C-reactive protein on complement activation: a possible
      complement regulatory role of modified or monomeric C-reactive protein in
      atherosclerotic lesions.
AB  - OBJECTIVE: The capacity of human C-reactive protein (CRP) to activate/regulate
      complement may be an important characteristic that links CRP and inflammation
      with atherosclerosis. Recent advances suggest that in addition to classical
      pentameric CRP, a conformationally distinct isoform of CRP, termed modified or
      monomeric CRP (mCRP), may also play an active role in atherosclerosis. Although
      the complement activation behavior of CRP has been well established, the capacity
      of mCRP to interact with and activate the complement cascade is unknown. METHODS
      AND RESULTS: mCRP bound avidly to purified C1q, and this binding occurred
      primarily through collagen-like region of C1q. Fluid phase mCRP inhibited the
      activation of complement cascade via engaging C1q from binding with other
      complement activators. In contrast, when immobilized or bound to oxidized or
      enzymatically modified low-density lipoprotein, mCRP could activate classical
      complement pathway. Low-level generation of sC5b-9 indicated that the activation
      largely bypassed the terminal sequence of complement, which appears to involve
      recruitment of Factor H. CONCLUSIONS: These results indicate that mCRP can both
      inhibit and activate the classical complement pathway by binding C1q, depending
      on whether it is in fluid phase or surface-bound state.

PMID- 16456096
TI  - Role of circulating vascular progenitors in angiogenesis, vascular healing, and
      pulmonary hypertension: lessons from animal models.
AB  - Accumulating evidence suggests that circulating progenitors contribute to
      vascular healing and remodeling under physiological and pathological conditions.
      Although there is growing enthusiasm for therapeutic and diagnostic application
      of bone marrow-derived progenitors, there are concerns that transplanted
      precursors or bone marrow cells may participate in the pathogenesis of
      unfavorable diseases such as cancer, retinopathy, and atherosclerosis. This
      review summarizes recent findings obtained from animal models to examine the
      roles of circulating vascular progenitor cells in angiogenesis, pulmonary
      hypertension, and vascular healing.

PMID- 16456097
TI  - Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein
      aggravates atherosclerosis.
AB  - OBJECTIVE: Atherosclerosis is associated with immune responses to oxidized low
      density lipoprotein (oxLDL). The presence of activated macrophages and T cells in
      lesions suggests that cell-mediated immune reactions are taking place during the
      disease process. However, the role of specific immune responses has remained
      unclear. We have previously shown that transfer of CD4+ T cells from
      apolipoprotein E knockout mice (apoE(-/-)) into immunodeficient apoE(-/-)
      scid/scid mice accelerates disease. METHODS AND RESULTS: To test whether this
      effect is dependent on specific disease-associated antigens, purified CD4+ T
      cells from oxLDL-immunized mice were transferred into apoE(-/-) scid/scid mice.
      CD4+ T cells from mice immunized with a nonrelevant antigen, keyhole limpet
      hemocyanin (KLH), and naive CD4+ T cells were used as controls. After 12 weeks,
      all mice that received T cells had larger lesions than untouched apoE(-/-)
      scid/scid controls. However, mice receiving CD4+ T cells from oxLDL immunized
      mice had substantially accelerated lesion progression compared with those
      receiving naive or KLH-primed T cells. Circulating levels of interferon-gamma
      were increased in proportion to the acceleration of atherosclerosis. CONCLUSIONS:
      These data show that adoptive transfer of purified CD4+ T cells from oxLDL
      immunized mice accelerates atherosclerosis. They support the notion that Th1
      cellular immunity is proatherogenic and identify oxLDL as a culprit autoantigen.

PMID- 16456098
TI  - Spontaneous coronary vasospasm in KATP mutant mice arises from a smooth muscle
      extrinsic process.
AB  - In the vasculature, ATP-sensitive potassium channels (KATP) channels regulate
      vascular tone. Mice with targeted gene disruptions of KATP subunits expressed in
      vascular smooth muscle develop spontaneous coronary vascular spasm and sudden
      death. From these models, it was hypothesized that the loss of KATP channel
      activity in arterial vascular smooth muscle was responsible for coronary artery
      spasm. We now tested this hypothesis using a transgenic strategy where the full
      length sulfonylurea receptor containing exon 40 was expressed under the control
      of a smooth muscle-specific SM22alpha promoter. Two transgenic founder lines were
      generated and independently bred to sulfonylurea receptor 2 (SUR2) null mice to
      generate mice that restored expression of KATP channels in vascular smooth
      muscle. Transgenic expression of the sulfonylurea receptor in vascular smooth
      muscle cells was confirmed by detecting mRNA and protein from the transgene.
      Functional restoration was determined by recording pinacidil-based KATP current
      by whole cell voltage clamping of isolated aortic vascular smooth muscle cells
      isolated from the transgenic restored mice. Despite successful restoration of
      KATP channels in vascular smooth muscle, transgene-restored SUR2 null mice
      continued to display frequent episodes of spontaneous ST segment elevation,
      identical to the phenotype seen in SUR2 null mice. As in SUR2 null mice, ST
      segment elevation was frequently followed by atrioventricular heart block. ST
      segment elevation and coronary perfusion pressure in the restored mice did not
      differ significantly between transgene-negative and transgene-positive SUR2 null
      mice. We conclude that spontaneous coronary vasospasm and sudden death in SUR2
      null mice arises from a coronary artery vascular smooth muscle-extrinsic process.

PMID- 16456099
TI  - Endogenous RGS proteins and Galpha subtypes differentially control muscarinic and
      adenosine-mediated chronotropic effects.
AB  - Cardiac automaticity is controlled by G protein-coupled receptors, such as
      adrenergic, muscarinic, and adenosine receptors. The strength and duration of G
      protein signaling is attenuated by regulator of G protein signaling (RGS)
      proteins acting as GTPase-activating proteins for Galpha subunits; however,
      little is known about the role of endogenous RGS proteins in cardiac function. We
      created point mutations in Galpha subunits that disrupt Galpha-RGS binding and
      introduced them into embryonic stem (ES) cells by homologous recombination.
      Spontaneously contacting cardiocytes derived from the ES cells were used to
      evaluate the role of endogenous RGS proteins in chronotropic regulation. The RGS
      insensitive GalphaoG184S homozygous knock-in (GalphaoGS/GS) cells demonstrated
      enhanced adenosine A1 and muscarinic M2 receptor-mediated bradycardic responses.
      In contrast, Galphai2GS/GS cells showed enhanced responses to M2 but not A1
      receptors. Similarly M2 but not A1 bradycardic responses were dramatically
      enhanced in Galphai2GS/GS mice. Blocking G protein-coupled inward rectifying K+
      (GIRK) channels largely abolished the mutation-induced enhancement of the M2
      receptor-mediated response but had a minimal effect on A1 responses. The Galphas
      dependent stimulation of beating rate by the beta2 adrenergic receptor agonist
      procaterol was significantly attenuated in GalphaoGS/GS and nearly abolished in
      Galphai2GS/GS cells because of enhanced signaling via a pertussis toxin sensitive
      mechanism. Thus, endogenous RGS proteins potently reduce the actions of
      Galpha(i/o)-linked receptors on cardiac automaticity. Furthermore, M2 and A1
      receptors differentially use Galphai2 and Galphao and associated downstream
      effectors. Thus, alterations in RGS function may play a role in
      pathophysiological processes and RGS proteins could represent novel
      cardiovascular therapeutic targets.

PMID- 16456100
TI  - Foxc2 is a common mediator of insulin and transforming growth factor beta
      signaling to regulate plasminogen activator inhibitor type I gene expression.
AB  - Elevated plasma levels of plasminogen activator inhibitor type I (PAI-1), a
      significant risk factor of ischemic heart disease, are associated with insulin
      resistance in which insulin and transforming growth factor (TGF)-beta play a
      pivotal role in regulating PAI-1 production. Forkhead transcription factor FOXC2
      is an important regulator of insulin resistance. However, the underlying
      molecular mechanisms to link FOXC2 to PAI-1 levels in insulin resistance remain
      to be elucidated. Here, we demonstrate that Foxc2 is a common transcriptional
      activator of insulin and TGF-beta signaling to directly regulate PAI-1 expression
      via 2 distinct target sites, an insulin response element (IRE) and a novel
      forkhead-binding element (FBE), adjacent to a Smad-binding site. We found that in
      adipocytes and endothelial cells Foxc2 mediates insulin action competing with
      another Forkhead protein, FOXO1, via the insulin response element, and
      simultaneously cooperate with the TGF-beta/Smad pathway to transactivate PAI-1.
      Importantly, Foxc2 haploinsufficiency in mice significantly attenuates TGF-beta1
      induced PAI-1 expression in the cardiovascular system and adipose tissue. Taken
      together, we propose that Foxc2 is a key molecule to regulate PAI-1 gene
      expression.

PMID- 16456101
TI  - Identification of prostaglandin E2 receptor subtype 2 as a receptor activated by
      OxPAPC.
AB  - Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC),
      which has been shown to accumulate in atherosclerotic lesions and other sites of
      chronic inflammation, activates endothelial cells (EC) to bind monocytes by
      activation of endothelial beta1 integrin and subsequent deposition of fibronectin
      on the apical surface. Our previous studies suggest this function of OxPAPC is
      mediated via a Gs protein-coupled receptor (GPCR). PEIPC (1-palmitoyl-2
      epoxyisoprostane E2-sn-glycero-3-phosphorylcholine) is the most active lipid in
      OxPAPC that activates this pathway. We screened a number of candidate GPCRs for
      their interaction with OxPAPC and PEIPC, using a reporter gene assay; we
      identified prostaglandin E2 receptor EP2 and prostaglandin D2 receptor DP as
      responsive to OxPAPC. We focused on EP2, which is expressed in ECs, monocytes,
      and macrophages. OxPAPC component PEIPC, but not POVPC, activated EP2 with an
      EC50 of 108.6 nmol/L. OxPAPC and PEIPC were also able to compete with PGE2 for
      binding to EP2 in a ligand-binding assay. The EP2 specific agonist butaprost was
      shown to mimic the effect of OxPAPC on the activation of beta1 integrin and the
      stimulation of monocyte binding to endothelial cells. Butaprost also mimicked the
      effect of OxPAPC on the regulation of tumor necrosis factor-alpha and interleukin
      10 in monocyte-derived cells. EP2 antagonist AH6809 blocked the activation of EP2
      by OxPAPC in HEK293 cells and blocked the interleukin-10 response to PEIPC in
      monocytic THP-1 cells. These results suggest that EP2 functions as a receptor for
      OxPAPC and PEIPC, either as the phospholipid ester or the released fatty acid, in
      both endothelial cells and macrophages.

PMID- 16456102
TI  - Platelet-derived growth factor BB-mediated normalization of dermal interstitial
      fluid pressure after mast cell degranulation depends on beta3 but not beta1
      integrins.
AB  - Interstitial fluid pressure (PIF) is one of the determinants of transcapillary
      fluid flux and thereby interstitial fluid volume. Cell-mediated control of PIF
      regulates fluid content in the loose interstitial connective tissues that
      surround the capillary bed. To maintain a normal PIF in dermis, beta1 integrins
      mediate the tensile strength applied by connective tissue cells on the
      extracellular matrix. Platelet-derived growth factor (PDGF)-BB normalizes
      anaphylaxis-induced reduction of PIF. Anti-beta3 integrin IgG and a cyclic RGD
      peptide that inhibits the alphaVbeta3 integrin blocked the ability of PDGF-BB to
      normalize the lowered PIF resulting from mast cell degranulation. PDGF-BB was
      unable to normalize PIF lowered as a result of mast cell degranulation in beta3
      negative mice. Monoclonal anti-beta3 integrin IgG had no effect on PIF in normal
      mouse dermis. In contrast, administration of anti-beta1 integrin IgM lowered PIF
      in normal dermis but had no effect on PDGF-BB-induced normalization of PIF after
      anaphylaxis. Furthermore, collagen gel contraction mediated by wild-type mouse
      embryonal fibroblasts were only marginally affected by function-blocking anti
      beta1 integrin antibodies, especially in the presence of PDGF-BB. In contrast,
      contraction mediated by alphaV-negative mouse embryonic fibroblasts was
      completely blocked by anti-beta1 integrin antibodies, even after stimulation with
      PDGF-BB. These results show a previously unrecognized in vivo function for the
      alphaVbeta3 integrin, as a participant in the control of PIF during inflammatory
      reactions. Furthermore, our data demonstrate that PDGF-BB induces connective
      tissue cells to generate tensile forces via alphaVbeta3 during such reactions.

PMID- 16456103
TI  - An in vivo analysis of hematopoietic stem cell potential: hematopoietic origin of
      cardiac valve interstitial cells.
AB  - Recent studies evaluating hematopoietic stem cell (HSC) potential raise the
      possibility that, in addition to embryonic sources, adult valve fibroblasts may
      be derived from HSCs. To test this hypothesis, we used methods that allow the
      potential of a single HSC to be evaluated in vivo. This was achieved by isolation
      and clonal expansion of single lineage-negative (Lin-), c-kit(+), Sca-1(+), CD34-
      cells from the bone marrow of mice that ubiquitously express enhanced green
      fluorescent protein (EGFP) combined with transplantation of individual clonal
      populations derived from these candidate HSCs into a lethally irradiated congenic
      non-EGFP mouse. Histological analyses of valve tissue from clonally engrafted
      recipient mice revealed the presence of numerous EGFP+ cells within host valves.
      A subpopulation of these cells exhibited synthetic properties characteristic of
      fibroblasts, as evidenced by their expression of mRNA for procollagen 1alpha1.
      Further, we show by Y-chromosome-specific fluorescence in situ hybridization
      analysis of female-to-male transplanted mice that the EGFP+ valve cells are the
      result of HSC-derived cell differentiation and not the fusion of EGFP+ donor
      cells with host somatic cells. Together, these findings demonstrate HSC
      contribution to the adult valve fibroblast population.

PMID- 16456104
TI  - Inseparably tied: functional and antioxidative capacity of endothelial progenitor
      cells.

PMID- 16456105
TI  - Mechanisms of endothelial cell heterogeneity in health and disease.

PMID- 16456106
TI  - Going with the flow: smooth muscle TRPM7 channels and the vascular response to
      blood flow.

PMID- 16456107
TI  - "Ryanogate": who leaked the calcium?

PMID- 16456108
TI  - Xanthine oxidase inhibition and heart failure: novel therapeutic strategy for
      ventricular dysfunction?

PMID- 16456109
TI  - Spatio-temporal diversity of apoptosis within the vascular wall in pulmonary
      arterial hypertension: heterogeneous BMP signaling may have therapeutic
      implications.

PMID- 16456110
TI  - Role of small GTPases in endothelial cytoskeletal dynamics and the shear stress
      response.
AB  - Fluid shear stress caused by blood flow is a major determinant of vascular
      remodeling and arterial tone and can lead to development of atherosclerosis. The
      endothelial monolayer in vivo acts as a signal transduction interface for
      hemodynamic forces; these forces determine the shape, cytoskeletal organization,
      and function of endothelial cells, allowing the vessels to cope with
      physiological or pathological conditions. The Ras superfamily of GTPases have
      been revealed to be master regulators of many cellular activities. In particular,
      the GTPases RhoA, Rac1, and Cdc42 are known to regulate cell shape changes
      through effects on the cytoskeleton, but their ability to influence polarity,
      microtubule dynamics, and transcription factor activity is just as significant.
      Shear stress modulates the activity of small GTPases, which are critical for both
      cytoskeletal reorganization and changes in gene expression in response to shear
      stress. The goal of this article is to review what is known about Ras and more so
      about Rho GTPases in mechanotransduction and the responses of cells to fluid
      flow. Several distinct signaling pathways can be coordinately activated by flow,
      and small GTPases are strongly implicated in some of them; thus possible
      connections will be explored and a unifying hypothesis offered.

PMID- 16456111
TI  - Early growth response-1 in cardiovascular pathobiology.
AB  - The immediate-early gene product and zinc finger transcription factor early
      growth response (Egr)-1 plays a key master regulatory role in multiple
      cardiovascular pathological processes. This article reviews the amazing recent
      evidence implicating Egr-1 in atherosclerosis, intimal thickening after acute
      vascular injury, ischemic pathology, angiogenesis, allograft rejection, and
      cardiac hypertrophy.

PMID- 16456116
TI  - The new standing guideline committee policy of the American Stroke Association
      Stroke Council.

PMID- 16456117
TI  - Correlation of cerebrovascular symptoms and microembolic signals with the
      stratified gray-scale median analysis and color mapping of the carotid plaque.
AB  - BACKGROUND AND PURPOSE: To determine whether a stratified gray-scale median (GSM)
      analysis of the carotid plaque combined with color mapping correlated better with
      the presence of neurological symptoms and microembolic signals (MES) than a whole
      plaque measurement. METHODS: A total of 131 patients presenting 167 carotid
      stenoses between 30% and 99% were analyzed by ultrasound. Emboli detection was
      performed by transcranial Doppler. For each plaque, the GSM values at depth 0 mm
      (surface) and at one third (30) and one half (50) of the plaque thickness were
      compared with the values obtained for the whole plaque. The plaque pixels were
      mapped into 3 colors: red, yellow and green, depending on their GSM value.
      RESULTS: Mean GSM values were lower among symptomatic plaques, but a
      statistically significant difference between values of the whole plaque and those
      of the surface was obtained only for MES+ stenoses (P<0.01). In a proportional
      odds logistic regression model based on 4 subgroups with an increasing clinical
      risk (MES-/symptoms-; MES-/symptoms+; MES+/symptoms-; +; MES+/symptoms+), low
      mean GSM values and the predominant red color at the surface were independent
      factors associated with the presence of symptoms or MES (P<0.0005). Furthermore,
      compared with a whole plaque measurement, analysis of the surface values
      predicted systematically with a greater sensitivity and specificity (receiver
      operating characteristic curves) each one of these 4 subgroups. CONCLUSIONS: Low
      mean GSM values and predominance of the red color at the surface correlated with
      most of the symptomatic or MES+ stenoses. This combined approach should be
      further investigated in a longitudinal study.

PMID- 16456121
TI  - Anterior-posterior ground reaction forces as a measure of paretic leg
      contribution in hemiparetic walking.
AB  - BACKGROUND AND PURPOSE: Walking after stroke is characterized by slow gait speed,
      poor endurance, reduced quality and adaptability of walking patterns, and an
      inability to coordinate the legs. Estimates based on mechanical work calculations
      have suggested that the paretic leg does 30% to 40% of the total mechanical work
      over the gait cycle, regardless of hemiparetic severity, but these work estimates
      may not describe the contribution of each leg to forward propulsion. The purpose
      of this study was to establish a quantifiable link between hemiparetic severity
      and paretic leg contribution to propulsion during walking, which we propose to
      quantify using a measure based on the anterior-posterior ground reaction forces
      (A-P GRFs). METHODS: A total of 47 participants with chronic hemiparesis walked
      at self-selected speeds to collect spatiotemporal parameters and 3D GRFs. A 16
      person subset also participated in a pedaling protocol to compare A-P GRF
      measures to established measures of paretic leg output. RESULTS: A-P GRF measures
      were correlated with both walking speed and hemiparetic severity. These measures
      were also strongly correlated with positive work and net work values obtained
      during the pedaling task. The percentage of total propulsion generated by the
      paretic leg (PP) was calculated and found to be 16%, 36%, and 49% for those with
      high, moderate, and low hemiparetic severity, respectively. CONCLUSIONS: PP was
      found to provide a quantitative measure of the coordinated output of the paretic
      leg. Further research on this measure of forward propulsion may lead to the
      provision of an effective tool for distinguishing functional compensation from
      physiological restitution.

PMID- 16456122
TI  - What patients want: consumer involvement in the design of a randomized controlled
      trial of routine oxygen supplementation after acute stroke.
AB  - BACKGROUND AND PURPOSE: To involve stroke patients and carers in the design of a
      study of oxygen supplementation in acute stroke and to obtain their views on the
      importance of the study, consent issues, relevance, and acceptability of the
      outcome measures, and the preferred method of follow-up. METHODS: This study
      involved qualitative and quantitative research. Three focus group meetings were
      held with individuals who have had personal experience of stoke, mostly stoke
      patients and their partners or carers (an association of young stroke sufferers
      and 2 dysphasia support groups each from a different town in the West Midlands,
      UK). The researchers explained the planned oxygen supplementation study and
      encouraged participants to comment and make suggestions in a semistructured
      interview. The audience was then asked to complete a questionnaire relating to
      the study. RESULTS: Seventy-three people (67% stroke patients and 33% carers;
      mean age 64; range 31 to 86 years; and 47% males) attended the 3 meetings. The
      overall response rate to the questionnaires was 70%. Most of the respondents
      considered the study worthwhile (97%) and the planned outcome measures relevant.
      In addition, assessment of speech, memory, sleep, and cognitive function was
      raised by >20% of respondents as important outcomes. Seventy-five percent would
      agree with assent from a family member on behalf of incompetent patients, and 92%
      would agree to a doctor recruiting incompetent patients to the study and seeking
      consent/assent later. The majority of respondents (80%) preferred personal
      contact with the researcher or a representative to a questionnaire for follow-up.
      CONCLUSIONS: Involvement of stroke patients and carers helped us identify outcome
      measures that are important to the stroke population but not routinely addressed
      in stroke assessment scales. A high proportion of respondents asked for waiver of
      consent and agreed to family's assent on behalf of incompetent patients. Although
      consumer involvement has helped us to make the study more relevant to the public,
      it has also led to difficult scientific and ethical conflicts in protocol design.

PMID- 16456123
TI  - Peroxynitrite diminishes myogenic activity and is associated with decreased
      vascular smooth muscle F-actin in rat posterior cerebral arteries.
AB  - BACKGROUND AND PURPOSE: This study investigated the effect of peroxynitrite (ONOO
      ) on pressure-induced myogenic activity and vascular smooth muscle (VSM) actin of
      isolated posterior cerebral arteries (PCAs). METHODS: Histochemical staining of
      nitrotyrosine (NT) was used to demonstrate the presence of ONOO- in the
      cerebrovasculature after 1 hour of middle cerebral artery occlusion with 30
      minutes of reperfusion. To determine the effect of ONOO- on pressure-induced
      myogenic activity, third-order PCAs from nonischemic animals were isolated and
      mounted in an arteriograph chamber. Diameter in response to changes in pressure
      was determined in the absence and presence of ONOO- (10(-8) to 10(-4) mol/L).
      Filamentous actin (F-actin) and globular actin (G-actin) were quantified using
      confocal microscopy in PCAs with and without exposure to ONOO-. RESULTS: NT
      staining of vascular cells was greater in ischemic brain versus sham animals
      (56+/-3% versus 35+/-3%; P<0.01). Addition of low concentrations of ONOO- (< or
      =10(-6) mol/L) to isolated PCAs caused constriction from 129+/-16 microm to 115+/
      15 microm (P<0.01), whereas concentrations >10(-6) mol/L caused dilation of
      spontaneous tone and loss of myogenic activity in the physiological range of 50
      to 125 mm Hg, increasing diameter from 130+/-6 to 201+/-5 microm at 75 mm Hg
      (P<0.01). In addition, the diminished myogenic activity was associated with a 4.5
      fold decrease in F-actin content of VSM and a 27% increase in G-actin content
      (P<0.01). CONCLUSIONS: This study demonstrates that ONOO- affects the myogenic
      activity of cerebral arteries and causes F-actin depolymerization in VSM, a
      consequence that could promote vascular damage during reperfusion injury and
      further brain injury.

PMID- 16456124
TI  - Role of CT angiography in thrombolysis decision-making for patients with presumed
      seizure at stroke onset.
AB  - BACKGROUND AND PURPOSE: The presence of seizure at stroke onset is a
      contraindication for intravenous tissue plasminogen activator treatment. A
      significant proportion of these patients' deficits are not attributable to Todd's
      paralysis and could be attributable to reversible ischemia. Currently there are
      no established methods of differentiating Todd's paralysis from ischemic
      stroke/early seizure. We sought to determine whether computed tomographic
      angiography (CTA) can be helpful in differentiating the 2. METHODS: Three hundred
      and twenty six patients underwent noncontrast CT and CTA for acute stroke at our
      institution over 3 years (June 2002 to April 2005). Of them, 116 had disabling
      deficits and presented within 3 hours. We reviewed the clinical data, noncontrast
      CT, CTA, electroencephalogram and outcome of these patients and identified those
      who presented with presumed seizure activity at stroke onset (seizure or altered
      consciousness at stroke onset). RESULTS: Nine (7.7%) patients had a concern of
      seizure at stroke onset. Median age 73 years (range, 31 to 85 years), median
      National Institutes of Health Stroke Scale (NIHSS) score 12 (range, 5 to 29). CTA
      showed proximal middle cerebral artery occlusion in 2 and distal middle cerebral
      artery occlusion in 3 patients. All 5 of these patients had evidence of
      infarction on follow-up (stroke+early seizure group-intracranial occlusion
      present). Three of these patients received intravenous tissue plasminogen
      activator because they were deemed to have "ischemic tissue at risk". Four
      patients had normal CT and CTA studies and recovered completely in 24 hours
      (Todd's paralysis only group-intracranial occlusion negative). CONCLUSIONS:
      Seizure at stroke onset was relatively uncommon in a consecutive cohort of acute
      stroke patients. CTA was a useful modality in differentiating Todd's paralysis
      from early seizure and ischemia by detection of intracranial occlusion and may
      contribute to decision-making for thrombolysis.

PMID- 16456125
TI  - Improved safety of hematopoietic transplantation with monkey embryonic stem cells
      in the allogeneic setting.
AB  - Cynomolgus monkey embryonic stem cell (cyESC)-derived in vivo hematopoiesis was
      examined in an allogeneic transplantation model. cyESCs were induced to
      differentiate into the putative hematopoietic precursors in vitro, and the cells
      were transplanted into the fetal cynomolgus liver at approximately the end of the
      first trimester (n = 3). Although cyESC-derived hematopoietic colony-forming
      cells were detected in the newborns (4.1%-4.7%), a teratoma developed in all
      newborns. The risk of tumor formation was high in this allogeneic transplantation
      model, given that tumors were hardly observed in immunodeficient mice or fetal
      sheep that had been xeno-transplanted with the same cyESC derivatives. It turned
      out that the cyESC-derived donor cells included a residual undifferentiated
      fraction positive for stage-specific embryonic antigen (SSEA)-4 (38.2% +/- 10.3%)
      despite the rigorous differentiation culture. When an SSEA-4-negative fraction
      was transplanted (n = 6), the teratoma was no longer observed, whereas the cyESC
      derived hematopoietic engraftment was unperturbed (2.3%-5.0%). SSEA-4 is
      therefore a clinically relevant pluripotency marker of primate embryonic stem
      cells (ESCs). Purging pluripotent cells with this surface marker would be a
      promising method of producing clinical progenitor cell preparations using human
      ESCs.

PMID- 16456126
TI  - Cellular memory and hematopoietic stem cell aging.
AB  - Hematopoietic stem cells (HSCs) balance self-renewal and differentiation in order
      to sustain lifelong blood production and simultaneously maintain the HSC pool.
      However, there is clear evidence that HSCs are subject to quantitative and
      qualitative exhaustion. In this review, we briefly discuss several known aspects
      of the stem cell aging process, including DNA damage, telomere shortening, and
      oxidative stress. Besides these known players, there is increasing evidence that
      higher order chromatin structure, largely defined by the histone code and
      affecting transcriptional activity, is important. A model is suggested which
      describes how epigenetic regulation of gene transcription by modulation of the
      chromatin structure in stem cells can account for regulation of the aging
      program.

PMID- 16456127
TI  - Hematopoietic engraftment of human embryonic stem cell-derived cells is regulated
      by recipient innate immunity.
AB  - Human embryonic stem cells (hESCs) provide an important means to characterize
      early stages of hematopoietic development. However, the in vivo potential of hESC
      derived hematopoietic cells has not been well defined. We demonstrate that hESC
      derived cells are capable of long-term hematopoietic engraftment when
      transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID)
      mice. Human CD45(+) and CD34(+) cells are identified in the mouse bone marrow
      (BM) more than 3 months after injection of hESCs that were allowed to
      differentiate on S17 stromal cells for 7-24 days. Secondary engraftment studies
      further confirm long-term repopulating cells derived from hESCs. We also
      evaluated two mechanisms that may inhibit engraftment: host immunity and
      requirement for homing to BM. Treatment with anti-ASGM1 antiserum that primarily
      acts by depletion of natural killer cells in transplanted mice leads to improved
      engraftment, likely due to low levels of HLA class I expressed on hESCs and
      CD34(+) cells derived from hESCs. Intra-BM injection also provided stable
      engraftment, with hematopoietic cells identified in both the injected and contra
      lateral femur. Importantly, no teratomas are evident in animals injected with
      differentiated hESCs. These results demonstrate that SCID-repopulating cells, a
      close surrogate for hematopoietic stem cells, can be derived from hESCs.
      Moreover, both adaptive and innate immune effector cells may be barriers to
      engraftment of these cells.

PMID- 16456128
TI  - Reverse serial analysis of gene expression (SAGE) characterization of orphan SAGE
      tags from human embryonic stem cells identifies the presence of novel transcripts
      and antisense transcription of key pluripotency genes.
AB  - Serial analysis of gene expression (SAGE) is a powerful technique for the
      analysis of gene expression. A significant portion of SAGE tags, designated as
      orphan tags, however, cannot be reliably assigned to known transcripts. We used
      an improved reverse SAGE (rSAGE) strategy to convert human embryonic stem cell
      (hESC)-specific orphan SAGE tags into longer 3' cDNAs. We show that the
      systematic analysis of these 3' cDNAs permitted the discovery of hESC-specific
      novel transcripts and cis-natural antisense transcripts (cis-NATs) and improved
      the assignment of SAGE tags that resulted from splice variants,
      insertion/deletion, and single-nucleotide polymorphisms. More importantly, this
      is the first description of cis-NATs for several key pluripotency markers in
      hESCs and mouse embryonic stem cells, suggesting that the formation of short
      interfering RNA could be an important regulatory mechanism. A systematic large
      scale analysis of the remaining orphan SAGE tags in the hESC SAGE libraries by
      rSAGE or other 3' cDNA extension strategies should unravel additional novel
      transcripts and cis-NATs that are specifically expressed in hESCs. Besides
      contributing to the complete catalog of human transcripts, many of them should
      prove to be a valuable resource for the elucidation of the molecular pathways
      involved in the self-renewal and lineage commitment of hESCs.

PMID- 16456129
TI  - Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and
      bone morphogenic protein pathways in human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) self-renew indefinitely while maintaining
      pluripotency. The molecular mechanism underlying hESCs self-renewal and
      pluripotency is poorly understood. To identify the signaling pathway molecules
      that maintain the proliferation of hESCs, we performed a microarray analysis
      comparing an aneuploid H1 hESC line (named H1T) versus euploid H1 hESC line
      because the H1T hESC line demonstrates a self-renewal advantage while maintaining
      pluripotency. We find differential gene expression for the Nodal/Activin,
      fibroblast growth factor (FGF), Wnt, and Hedgehog (Hh) signaling pathways in the
      H1T line, which implicates each of these molecules in maintaining the
      undifferentiated state, whereas the bone morphogenic protein (BMP) and Notch
      pathways could promote hESCs differentiation. Experimentally, we find that
      Activin A is necessary and sufficient for the maintenance of self-renewal and
      pluripotency of hESCs and supports long-term feeder and serum-free growth of
      hESCs. We show that Activin A induces the expression of Oct4, Nanog, Nodal, Wnt3,
      basic FGF, and FGF8 and suppresses the BMP signal. Our data indicates Activin A
      as a key regulator in maintenance of the stemness in hESCs. This finding will
      help elucidate the complex signaling network that maintains the hESC phenotype
      and function.

PMID- 16456130
TI  - Mesenchymal stem cells and adipogenesis in hemangioma involution.
AB  - Hemangioma is a benign tumor of infancy whose hallmark is rapid growth during the
      first year of life followed by slow regression during early childhood. The
      proliferating phase is characterized by abundant immature endothelial cells, the
      involuting phase by prominent endothelial-lined vascular channels and endothelial
      apoptosis, and the involuted phase by few remaining capillary-like vessels
      surrounded by loose fibrofatty tissue. Nothing is known about the mechanisms that
      contribute to the adipogenesis during this spontaneous regression. We postulated
      that mesenchymal stem cells (MSCs) reside in the tumor and preferentially
      differentiate into adipocytes. To test this hypothesis, we isolated MSCs from 14
      proliferating and five involuting hemangiomas by taking advantage of the well
      known selective adhesion of MSCs to bacteriologic dishes. These hemangioma
      derived MSCs (Hem-MSCs) are similar to MSCs obtained from human bone marrow,
      expressing the cell surface markers SH2 (CD105), SH3, SH4, CD90, CD29, smooth
      muscle alpha-actin, and CD133 but not the hematopoietic markers CD45 and CD14 or
      the hematopoietic/endothelial markers CD34, CD31, and kinase insert domain
      receptor (KDR). Hem-MSCs exhibited multilineage differentiation with robust
      adipogenic potential that correlated with the proliferating phase. The numbers of
      adipogenic Hem-MSCs were higher in proliferating-phase than in involuting-phase
      tumors and higher than in normal infantile skin. Furthermore, Hem-MSCs exhibited
      a random pattern of X-chromosomal inactivation, indicating that these cells are
      not clonally derived. In summary, we have identified MSCs as a novel cellular
      constituent in infantile hemangioma. These MSCs may contribute to the
      adipogenesis during hemangioma involution.

PMID- 16456131
TI  - Effects of aging and niche microenvironment on spermatogonial stem cell self
      renewal.
AB  - Aging is evident in most tissues and organ systems, but the mechanisms of aging
      are difficult to identify and poorly understood. Here, we test the hypothesis
      that aging results in uncorrected defects in stem cell and/or niche function,
      which lead to system failure. We used the spermatogonial stem cell (SSC)
      transplantation assay to determine the effect of aging on testis stem cell/niche
      function in mice. Between 12 and 24 months of age, male mice experienced a
      declining level of fertility associated with decreased testis weight, level of
      spermatogenesis, and total stem cell content. However, when stem cells were
      consecutively passaged at 3-month intervals to testes of young males, these stem
      cells continued to produce spermatogenesis for more than 3 years. Thus, SSC self
      renewal continues long past the normal life span of the animal when the stem cell
      is continually maintained in a young niche/microenvironment. Moreover, these data
      suggest that infertility in old males results from deterioration of the SSC niche
      and failure to support an appropriate balance between stem cell self-renewal and
      differentiation.

PMID- 16456132
TI  - Cell culture medium composition and translational adult bone marrow-derived stem
      cell research.
AB  - The growing body of adult bone marrow-derived stem cell research in regenerative
      medicine has recently entered the clinical transplantation setting. The need for
      a robust flow of data from basic to translational scientists is imperative. All
      animal- and/or human-derived products should ideally be excluded and synthetic
      recombinant alternatives used instead. A variety of reasons make such an approach
      favorable, including achievement of sounder control levels, reduction of any
      prion, viral, or zoonose contamination risk, avoidance of possible immunological
      reactions, as well as decrease in demand on animal supplies. At a preclinical
      level, investigative cell culture protocols must incorporate serum-free media
      groups alongside control conditions. Finally, autologous serum should not be
      neglected until an "off-the-shelf" alternative becomes available in the future.

PMID- 16456133
TI  - Differentiation of mouse embryonic stem cells after RNA interference-mediated
      silencing of OCT4 and Nanog.
AB  - RNA interference (RNAi) holds great promise as a tool to study the basic biology
      of stem cells or to direct differentiation in a specific manner. Barriers to
      achieving efficient and specific gene silencing in RNAi experiments include
      limitations in transfection efficiency and in the efficacy and specificity of
      RNAi silencing effectors. Here, we combine methods of efficient lipid-mediated
      delivery with chemically modified RNAi compounds to silence genes related to
      pluripotency, in order to direct differentiation of mouse embryonic stem cells.
      After transfection of embryonic stem cells with OCT4- or Nanog-targeted RNAi
      compounds, levels of OCT4 or Nanog transcript and protein were reduced
      accordingly. Reduction in OCT4 expression correlated with induction of
      trophectoderm genes Cdx2, Hand1, and PL-1, with formation of cells with
      trophoblast giant cell phenotype after 6 days. Reduction in Nanog expression
      correlated with induction of extraembryonic endoderm genes GATA4, GATA6, and
      laminin B1, with subsequent generation of groups of cells with parietal endoderm
      phenotype. Our results indicate that transient inhibition of OCT4 or Nanog by
      RNAi compounds is sufficient to induce differentiation toward extraembryonic
      lineages, which supports the model that these transcription factors function in a
      dose-dependent manner to influence cell fate.

PMID- 16456134
TI  - Derivation of distal lung epithelial progenitors from murine embryonic stem cells
      using a novel three-step differentiation protocol.
AB  - Embryonic stem cells (ESCs) are a potential source for the cell-based therapy of
      a wide variety of lung diseases for which the only current treatment is
      transplantation. However, distal lung epithelium, like many other endodermally
      derived somatic cell lineages, is proving difficult to obtain from both murine
      and human ESCs. We have previously obtained alveolar epithelium from ESCs,
      although final cell yield remained extremely low. Here, we present an optimized
      three-step protocol for the derivation of distal lung epithelial cells from
      murine ESCs. This protocol incorporates (a) treatment of early differentiating
      embryoid bodies with activin A to enhance the specification of the endodermal
      germ layer, followed by (b) adherent culture in serum-free medium and (c) the
      final application of a commercial, lung-specific medium. As well as enhancing the
      specification of distal lung epithelium, this protocol was found to yield cells
      with a phenotype most closely resembling that of lung-committed progenitor cells
      present in the foregut endoderm and the early lung buds during embryonic
      development. This is in contrast to our previous differentiation method, which
      drives differentiation through to mature type II alveolar epithelial cells. The
      derivation of a committed lung progenitor cell type from ESCs is particularly
      significant for regenerative medicine because the therapeutic implantation of
      progenitor cells has several clear advantages over the transplantation of mature,
      terminally differentiated somatic cells.

PMID- 16456135
TI  - Mechanisms underlying acceleration of blood flow recovery in ischemic limbs by
      macrophage colony-stimulating factor.
AB  - Recently we reported that macrophage colony-stimulating factor (M-CSF) can
      mobilize endothelial progenitor cells (EPCs) from the bone marrow into the
      peripheral blood, resulting in an increase in the number of blood vessels and
      augmentation of blood flow in the ischemia-induced legs. M-CSF accelerates
      neovascularization of ischemic lesions resulting from the mobilization of EPCs.
      In the present paper, we analyze the mechanisms underling the mobilization of
      EPCs by M-CSF. M-CSF augments the production of vascular endothelial growth
      factor (VEGF) from the bone marrow cells, especially from myeloid lineage cells.
      In vivo administration of anti-VEGF antibody abrogates both the acceleration of
      the recovery of blood flow in the ischemia-induced limbs by M-CSF and the
      augmentation of the mobilization of EPCs induced by M-CSF. These results suggest
      that the M-CSF contributes to rapid recovery of blood flow in ischemic lesions by
      mobilization of EPCs from the bone marrow through augmentation of VEGF production
      in the bone marrow and that the VEGF is mainly produced by myeloid lineage cells.

PMID- 16456136
TI  - Embryonic stem cell-derived neuronally committed precursor cells with reduced
      teratoma formation after transplantation into the lesioned adult mouse brain.
AB  - The therapeutic potential of embryonic stem (ES) cells in neurodegenerative
      disorders has been widely recognized, and methods are being developed to optimize
      culture conditions for enriching the cells of interest and to improve graft
      stability and safety after transplantation. Whereas teratoma formation rarely
      occurs in xenogeneic transplantation paradigms of ES cell-derived neural progeny,
      more than 70% of mice that received murine ES cell-derived neural precursor cells
      develop teratomas, thus posing a major safety problem for allogeneic and
      syngeneic transplantation paradigms. Here we introduce a new differentiation
      protocol based on the generation of substrate-adherent ES cell-derived neural
      aggregates (SENAs) that consist predominantly of neuronally committed precursor
      cells. Purified SENAs that were differentiated into immature but postmitotic
      neurons did not form tumors up to four months after syngeneic transplantation
      into the acutely degenerated striatum and showed robust survival.

PMID- 16456137
TI  - Identification of label-retaining cells in mouse endometrium.
AB  - Human and mouse endometrium (lining of the uterus) undergo cycles of growth and
      regression as part of each reproductive cycle. A well-known method to identify
      somatic stem/progenitor cells and their location in the stem cell niche is the
      label-retaining cell (LRC) approach. We hypothesized that mouse endometrium
      contains small populations of both epithelial and stromal somatic stem/progenitor
      cells that may be detected by the LRC technique. The overall objective of this
      study was to identify and quantify LRCs in mouse endometrium, to determine their
      location, and to identify their niche in this highly regenerative tissue.
      Endometrium was labeled for 3 days with bromodeoxyuridine (BrdU) in postnatal day
      3 (P3) mice prior to gland development and prepubertal (P19) mice after glands
      had formed, followed by chase periods of up to 12 weeks. After an 8-week chase,
      3% of epithelial nuclei immunostained with BrdU antibody and were considered
      epithelial LRCs. These were primarily located in the luminal epithelium.
      Epithelial LRCs did not express estrogen receptor-alpha (ER-alpha). Stromal LRCs
      (6%) were found adjacent to luminal epithelium, at the endometrial-myometrial
      junction, and near blood vessels after a 12-week chase. Stromal LRCs were stem
      cell antigen-1, CD45(-), and some (16%) expressed ER-alpha, indicating their
      capacity to respond to estrogen and transmit paracrine signals to epithelial
      cells for endometrial epithelium regeneration. Both epithelial LRCs and some
      stromal LRCs, mainly located at the endometrial-myometrial junction, were
      recruited into the cell cycle after estrogen-stimulated endometrial regeneration,
      indicating a functional response to proliferative signals. This study has
      demonstrated for the first time the presence of both epithelial and stromal LRCs
      in mouse endometrium, suggesting that these stem-like cells may be responsible
      for endometrial regeneration.

PMID- 16456138
TI  - Soluble mesothelin-related peptides in the diagnosis of malignant pleural
      mesothelioma.
AB  - BACKGROUND: Diagnosis of malignant pleural mesothelioma is a challenging issue.
      Potential markers in mesothelioma diagnosis include soluble mesothelin-related
      peptides (SMRPs) and osteopontin, but no subsequent validation has been published
      yet. METHODS: We prospectively evaluated SMRPs in serum and pleural effusion from
      patients with mesothelioma (n = 74), pleural metastasis of carcinomas (n = 35),
      or benign pleural lesions associated with asbestos exposure (n = 28), recruited
      when first suspected for mesothelioma. FINDINGS: Mean serum SMRP level was higher
      in patients with mesothelioma (2.05 +/- 2.57 nM/L [median +/- interquartile
      range]) than in patients with metastasis (1.02 +/- 1.79 nM/L) or benign lesions
      (0.55 +/- 0.59 nM/L). The area under the receiver operating characteristic curve
      (AUC) for serum SMRP was 0.872 for differentiating mesothelioma and benign
      lesions, cut-off = 0.93 nM/L (sensitivity = 80%, specificity = 82.6%). The AUC
      for serum SMRP differentiating metastasis and mesothelioma was 0.693, cut-off =
      1.85 nM/L (sensitivity = 58.3%, specificity = 73.3%). SMRP values in pleural
      fluid were higher than in serum in all groups (mesothelioma: 46.1 +/- 83.2 nM/L;
      benign lesions: 6.4 +/- 11.1 nM/L; metastasis: 6.36 +/- 21.73 nM/L). The AUC for
      pleural SMRP-differentiating benign lesions and mesothelioma was 0.831, cut-off =
      10.4 nM/L (sensitivity = 76.7%, specificity = 76.2%). The AUC for pleural SMRP
      differentiating metastasis and mesothelioma was 0.793. INTERPRETATION: We show
      that SMRPs may be a promising marker for mesothelioma diagnosis when measured
      either in serum or pleural fluid. The diagnostic value of SMRPs was similar in
      both types of samples, but pleural fluid SMRPs may better discriminate
      mesothelioma from pleural metastasis.

PMID- 16456139
TI  - Pulmonary arterial hypertension in France: results from a national registry.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is an orphan disease for which
      the trend is for management in designated centers with multidisciplinary teams
      working in a shared-care approach. OBJECTIVE: To describe clinical and
      hemodynamic parameters and to provide estimates for the prevalence of patients
      diagnosed for PAH according to a standardized definition. METHODS: The registry
      was initiated in 17 university hospitals following at least five newly diagnosed
      patients per year. All consecutive adult (> or = 18 yr) patients seen between
      October 2002 and October 2003 were to be included. MAIN RESULTS: A total of 674
      patients (mean +/- SD age, 50 +/- 15 yr; range, 18-85 yr) were entered in the
      registry. Idiopathic, familial, anorexigen, connective tissue diseases,
      congenital heart diseases, portal hypertension, and HIV-associated PAH accounted
      for 39.2, 3.9, 9.5, 15.3, 11.3, 10.4, and 6.2% of the population, respectively.
      At diagnosis, 75% of patients were in New York Heart Association functional class
      III or IV. Six-minute walk test was 329 +/- 109 m. Mean pulmonary artery
      pressure, cardiac index, and pulmonary vascular resistance index were 55 +/- 15
      mm Hg, 2.5 +/- 0.8 L/min/m(2), and 20.5 +/- 10.2 mm Hg/L/min/m(2), respectively.
      The low estimates of prevalence and incidence of PAH in France were 15.0
      cases/million of adult inhabitants and 2.4 cases/million of adult inhabitants/yr.
      One-year survival was 88% in the incident cohort. CONCLUSIONS: This contemporary
      registry highlights current practice and shows that PAH is detected late in the
      course of the disease, with a majority of patients displaying severe functional
      and hemodynamic compromise.

PMID- 16456140
TI  - Transmission of Mycobacterium tuberculosis undetected by tuberculin skin testing.
AB  - RATIONALE: The development of tuberculin skin test (TST) positivity following
      infection by Mycobacterium tuberculosis is not invariable and may depend on
      bacillary as well as host factors. OBJECTIVES: First, to compare the diagnostic
      performance of the TST and a form of in vitro IFN-gamma release assay (IFNGRA) in
      the circumstances of a contact investigation prompted by an unusually severe
      index case of infectious pulmonary tuberculosis. Second, to investigate the
      ability of the strain of M. tuberculosis responsible to induce cytokine secretion
      from monocytes in vitro. METHODS: A routine TST-based tuberculosis-contact
      screening procedure supplemented by the use of an "in house" IFNGRA that assays
      the T-cell response to the M. tuberculosis-specific antigens ESAT-6, CFP-10
      (presented as a fusion protein within the inactivated adenylate cyclase of
      Bordetella pertussis), and purified protein derivative of M. tuberculosis.
      Isolation and genetic typing of the strain of M. tuberculosis responsible, and
      investigation of its ability to induce cytokine secretion from monocytes in
      vitro. MEASUREMENTS AND MAIN RESULTS: TST screening suggested a low rate of
      transmission with just 2/75 unequivocally positive responses. By contrast, the
      IFNGRA suggested an infection rate of 16/75 (22%). When compared with two
      reference strains of M. tuberculosis (H37Rv and CDC1551), the outbreak strain
      induced lower levels of tumor necrosis factor-alpha and interleukin-12p40 (p <
      0.04), cytokines associated with the development of delayed-type
      hypersensitivity. CONCLUSIONS: These data suggest that infection by M.
      tuberculosis can be undetected by TST, and that this may partially relate to
      strain differences in immunogenicity.

PMID- 16456141
TI  - Respiratory syncytial virus, airway inflammation, and FEV1 decline in patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as an
      important pathogen in adults with cardiopulmonary disease. It has been associated
      with acute exacerbations of chronic obstructive pulmonary disease (COPD);
      however, it has also been detected in the lower airway in the stable state, but
      the consequences of RSV in stable disease have not previously been determined. We
      therefore studied the consequences of RSV persistence in adults with COPD and its
      effect on airway inflammation and lung function decline. METHODS: A total of 241
      sputum samples from 74 patients with COPD (FEV(1)% predicted, 39.2%;
      interquartile range, 29.6-57.8%) were collected quarterly in the stable state
      over 2 yr. RSV was detected by polymerase chain reaction (PCR), quantitative
      microbiology was performed, and inflammatory cytokines were quantified by ELISA.
      RESULTS: RSV RNA was detected in 32.8% of sputum samples. Patients in whom RSV
      was more frequently detected (> 50% of samples RSV PCR-positive, n=18) had higher
      airway inflammation and faster FEV(1) decline over the study (101.4 ml/yr [95%
      confidence interval, 57.1-145.8]) compared with those with less frequent
      detection of RSV (n=56; 51.2 ml/yr [31.7-70.8]; p=0.01). The observed
      relationship between RSV detection and accelerated lung function decline was
      independent of smoking status, exacerbation frequency, and lower airway bacterial
      load. CONCLUSIONS: Persistent RSV detection in patients with COPD is associated
      with airway inflammation and accelerated decline in FEV(1). Chronic RSV infection
      may be a novel therapeutic target to alter the natural history of COPD.

PMID- 16456142
TI  - Receptor for advanced glycation end-products is a marker of type I cell injury in
      acute lung injury.
AB  - RATIONALE: Receptor for advanced glycation end-products (RAGE) is one of the
      alveolar type I cell-associated proteins in the lung. OBJECTIVES: To test the
      hypothesis that RAGE is a marker of alveolar epithelial type I cell injury.
      METHODS: Rats were instilled intratracheally with 10 mg/kg lipopolysaccharide or
      hydrochloric acid. RAGE levels were measured in the bronchoalveolar lavage (BAL)
      and serum in the rats and in the pulmonary edema fluid and plasma from patients
      with acute lung injury (ALI; n = 22) and hydrostatic pulmonary edema (n = 11).
      MAIN RESULTS: In the rat lung injury studies, RAGE was released into the BAL and
      serum as a single soluble isoform sized approximately 48 kD. The elevated levels
      of RAGE in the BAL correlated well with the severity of experimentally induced
      lung injury. In the human studies, the RAGE level in the pulmonary edema fluid
      was significantly higher than the plasma level (p < 0.0001). The median edema
      fluid/plasma ratio of RAGE levels was 105 (interquartile range, 55-243). The RAGE
      levels in the pulmonary edema fluid from patients with ALI were higher than the
      levels from patients with hydrostatic pulmonary edema (p < 0.05), and the plasma
      RAGE level in patients with ALI were significantly higher than the healthy
      volunteers (p < 0.001) or patients with hydrostatic pulmonary edema (p < 0.05).
      CONCLUSION: RAGE is a marker of type I alveolar epithelial cell injury based on
      experimental studies in rats and in patients with ALI.

PMID- 16456143
TI  - Genetic association analysis of functional impairment in chronic obstructive
      pulmonary disease.
AB  - RATIONALE: Patients with severe chronic obstructive pulmonary disease (COPD) may
      have varying levels of disability despite similar levels of lung function. This
      variation may reflect different COPD subtypes, which may have different genetic
      predispositions. OBJECTIVES: To identify genetic associations for COPD-related
      phenotypes, including measures of exercise capacity, pulmonary function, and
      respiratory symptoms. METHODS: In 304 subjects from the National Emphysema
      Treatment Trial, we genotyped 80 markers in 22 positional and/or biologically
      plausible candidate genes. Regression models were used to test for association,
      using a test-replication approach to guard against false-positive results. For
      significant associations, effect estimates were recalculated using the entire
      cohort. Positive associations with dyspnea were confirmed in families from the
      Boston Early-Onset COPD Study. RESULTS: The test-replication approach identified
      four genes-microsomal epoxide hydrolase (EPHX1), latent transforming growth
      factor-beta binding protein-4 (LTBP4), surfactant protein B (SFTPB), and
      transforming growth factor-beta1 (TGFB1)-that were associated with COPD-related
      phenotypes. In all subjects, single-nucleotide polymorphisms (SNPs) in EPHX1 (p <
      or = 0.03) and in LTBP4 (p < or = 0.03) were associated with maximal output on
      cardiopulmonary exercise testing. Markers in LTBP4 (p < or = 0.05) and SFTPB (p =
      0.005) were associated with 6-min walk test distance. SNPs in EPHX1 were
      associated with carbon monoxide diffusing capacity (p < or = 0.04). Three SNPs in
      TGFB1 were associated with dyspnea (p < or = 0.002), one of which replicated in
      the family study (p = 0.02). CONCLUSIONS: Polymorphisms in several genes seem to
      be associated with COPD-related traits other than FEV(1). These associations may
      identify genes in pathways important for COPD pathogenesis.

PMID- 16456144
TI  - Associations of tumor necrosis factor G-308A with childhood asthma and wheezing.
AB  - RATIONALE: Tumor necrosis factor (TNF) mediates a spectrum of airway inflammatory
      responses, including those to air pollutants, and is an asthma candidate gene.
      One TNF promoter variant (G-308A) affects expression of TNF and has been
      associated with inflammatory diseases; however, studies of asthma have been
      inconsistent. Because ozone produces oxidative stress, increased airway TNF, and
      inflammation, the associations of the -308 TNF polymorphism with asthma may vary
      by ozone exposure and variants of oxidant defense genes glutathione-S-transferase
      (GST) M1 and GSTP1. OBJECTIVES: To investigate the association of TNF G-308A with
      asthma and wheezing and to determine whether these associations vary with ozone
      exposure and GSTM1 and GSTP1 genotype. METHODS: We studied associations of TNF
      308 genotype with lifetime and current wheezing and asthma among 3,699 children
      in the Children's Health Study. We examined differences in associations with
      community ozone and by GSTM1 null and GSTP1 105 Ile/Val (A105G) genotype.
      RESULTS: Children with TNF-308 GG had decreased risk of asthma (odds ratio, 0.8;
      95% confidence interval, 0.7-0.9) and lifetime wheezing (odds ratio, 0.8; 95%
      confidence interval, 0.7-0.9). The protective effects of GG genotype on wheezing
      outcomes were of greater magnitude in lower compared with higher ozone
      communities. These findings were replicated in the two cohorts of fourth-grade
      children recruited in 1993 and 1996. The reduction of the protective effect from
      the -308 GG genotype with higher ozone exposure was most marked in the GSTM1 null
      and GSTP1 Ile/Ile groups. CONCLUSIONS: The TNF-308 GG genotype may have a
      protective role in asthma pathogenesis, depending on airway oxidative stress
      levels.

PMID- 16456145
TI  - Bronchial thermoplasty for asthma.
AB  - RATIONALE: Bronchial thermoplasty (BT) reduces the potential for smooth muscle
      mediated bronchoconstriction by reducing the mass of smooth muscle in the walls
      of conducting airways. OBJECTIVES: This study was conducted to examine the safety
      and impact on lung function and airway responsiveness of BT over 2 yr. METHODS:
      The safety of BT was studied in 16 subjects with mild to moderate asthma.
      Baseline and 12-wk post-treatment measurements included spirometry, methacholine
      challenge, daily diary recordings of peak flow, symptoms, and medication usage.
      Subjects completed follow-up evaluations at 12 wk, 1 yr, and 2 yr. MEASUREMENTS
      AND MAIN RESULTS: The procedure was well tolerated; side effects were transient
      and typical of what is commonly observed after bronchoscopy. All subjects
      demonstrated improvement in airway responsiveness. The mean PC(20) increased by
      2.37 +/- 1.72 (p < 0.001), 2.77 +/- 1.53 (p = 0.007), and 2.64 +/- 1.52 doublings
      (p < 0.001), at 12 wk, 1 yr, and 2 yr post-procedure, respectively. Data from
      daily diaries collected for 12 wk indicated significant improvements over
      baseline in symptom-free days (p = 0.015), morning peak flow (p = 0.01), and
      evening peak flow (p < or = 0.007). Spirometry measurements remained stable
      throughout the study period. CONCLUSIONS: BT is well tolerated in patients with
      asthma and results in decreased airway hyperresponsiveness that persists for at
      least 2 yr.

PMID- 16456146
TI  - Lung function and exercise capacity in young adults born prematurely.
AB  - RATIONALE: Limited information is available about the long-term outcome of lung
      function and exercise capacity in young adults born prematurely. OBJECTIVE: To
      determine long-term effects of prematurity on lung function (volumes, diffusing
      capacity) and exercise capacity in ex-preterms compared with healthy peers.
      METHODS: In a prospective cohort study, children born with a gestational age of
      less than 32 wk and/or a birth weight under 1,500 g were followed up for 19 yr.
      Participants (n=42; mean gestational age, 30 wk, and mean birth weight, 1,246 g)
      and healthy term control subjects (n=48) were recruited for lung function and
      exercise tests. MEASUREMENTS: Spirometry, bodybox (TLC(box)), diffusing capacity
      (Dl(CO)), bicycle ergometer test. MAIN RESULTS: Preterm birth was associated with
      lower FEV(1) (preterms, 95% predicted, vs. controls, 110% predicted; p<0.001),
      DL(CO)sb (88% predicted vs. 96% predicted, p=0.003), and exercise capacity (load,
      185 vs. 216 W; p<0.001; anaerobic threshold: mean, 1,546 vs. 1,839 ml/min;
      p<0.001) compared with control subjects at follow-up. No differences between the
      groups were found in TLC(box), peak oxygen consumption (Vo(2)), and breathing
      reserve. No significant differences in lung function and exercise parameters were
      found between preterms with and without bronchopulmonary dysplasia. CONCLUSIONS:
      Long-term effects of prematurity were airway obstruction and a lower CO diffusing
      capacity compared with control subjects, although mean lung function parameters
      were within the normal range. Ex-preterms had a lower exercise level, which could
      not be explained by impaired lung function or smoking habits, but might be due to
      impaired physical fitness.

PMID- 16456147
TI  - A novel IkappaB kinase-beta inhibitor ameliorates bleomycin-induced pulmonary
      fibrosis in mice.
AB  - RATIONALE: IkappaB kinase-beta is a critical regulator in the activation of
      nuclear factor-kappaB (NF-kappaB), a transcription factor related to the
      expression and regulation of proinflammatory cytokines. OBJECTIVE: To evaluate if
      inhibition of IkappaB kinase-beta ameliorates pneumonitis and pulmonary fibrosis.
      METHODS: We examined whether a novel IkappaB kinase-beta inhibitor, IMD-0354,
      attenuates bleomycin-induced pulmonary fibrosis in mice. MEASUREMENTS AND MAIN
      RESULTS: Administration of IMD-0354 significantly improved the loss of body
      weight and survival of mice treated with bleomycin, whereas IMD-0354 alone did
      not cause any morphologic change in the lung. When mice were evaluated 28 d after
      bleomycin administration, IMD-0354 dose-dependently reduced the collagen content
      and fibrotic scores as shown by histologic examination. The findings in the
      bronchoalveolar lavage demonstrated that the proportions of neutrophils and
      lymphocytes were decreased in mice treated with IMD-0354 on Day 7 and 14,
      respectively. IMD-0354 treatment was confirmed to inhibit the activation of NF
      kappaB, but not activator protein-1, in the lungs treated with bleomycin. The
      production of inflammatory cytokines tumor necrosis factor-alpha and interleukin
      1beta was reduced in the lungs of mice treated with IMD-0354. CONCLUSIONS: These
      results suggest that IMD-0354 might be useful to ameliorate the inflammation in
      the lungs induced by fibrotic injury and the subsequent fibrogenesis via
      inhibiting the expression of profibrotic cytokines related to the activation of
      NF-kappaB.

PMID- 16456148
TI  - Uteroglobin-related protein 1 expression suppresses allergic airway inflammation
      in mice.
AB  - RATIONALE: Uteroglobin-related protein (UGRP) 1, which is highly expressed in the
      epithelial cells of the airways, has been suggested to play a role in lung
      inflammation. OBJECTIVES: The aim of study was to understand the effect of
      overexpressed UGRP1 on lung inflammation in a mouse model of allergic airway
      inflammation. METHODS: Ovalbumin-sensitized and -challenged mice, a model for
      allergic airway inflammation, were used in conjunction with recombinant
      adenovirus expressing UGRP1. MEASUREMENTS AND MAIN RESULTS: We demonstrated that
      intranasal administration of adeno-UGRP1 successfully delivered UGRP1 to the
      epithelial cells of airways and markedly reduced the number of infiltrating
      inflammatory cells, particularly eosinophils, in lung tissue as well as the level
      of proinflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-13 in
      bronchoalveolar lavage fluids. The healed phase of inflammation was clearly seen
      in the peripheral areas of adeno-UGRP1-treated mouse lungs. CONCLUSION: These
      results demonstrate that UGRP1 can suppress inflammation in the mouse model of
      allergic airway inflammation. Based on this result, we propose UGRP1 as a novel
      therapeutic candidate for treating lung inflammation such as is found in asthma.

PMID- 16456149
TI  - Intimate partner violence and women's depression before and during pregnancy.
AB  - Depressive symptoms of 95 prenatal care patients were examined relative to the
      women's experiences of intimate partner violence. Women who were victims of
      psychological aggression during the year before pregnancy were not at elevated
      risk for depression except when the psychological aggression was very frequent.
      However, during pregnancy, psychological aggression was more closely tied to
      women's depression levels, regardless of its frequency. In addition, women who
      experienced any level of physical assault or sexual coercion by their intimate
      partners (before or during pregnancy) had higher levels of depressive symptoms
      compared to nonvictims.

PMID- 16456150
TI  - The importance of spirituality in the lives of domestic violence survivors.
AB  - Women with abusive partners utilize a variety of coping strategies to deal with
      and heal from the violence and sense of betrayal they have experienced. For many
      women, their trust in a higher power and the support they receive from their
      faith community is integral to their healing. Of 151 women interviewed for this
      study, the majority (97%) noted that spirituality or God was a source of strength
      or comfort for them. Extent of religious involvement predicted increased
      psychological well-being and decreased depression. For women of color, greater
      religious involvement was also related to increased social support. Implications
      for research and direct services are discussed.

PMID- 16456151
TI  - Responding to the needs of older women experiencing domestic violence.
AB  - Older women experiencing domestic violence are an invisible group who fall into
      the gap between two forms of family violence: elder abuse and domestic violence.
      This article reviews the literature in both fields, describing each paradigm, how
      it explains and responds to its specific form of violence, and why neither has
      been able to provide an adequate response to domestic violence against older
      women. A collaborative response is needed, accounting for both the age and gender
      dimensions of the problem.

PMID- 16456152
TI  - Punitive action or gentle persuasion: exploring police officers' justifications
      for using dual arrest in domestic violence cases.
AB  - Mandatory and preferred arrest policies may be resulting in a backlash for
      victims who are arrested along with their batterers. Little prior research has
      explored why officers engage in dual arrests. The current study examines the
      rationales employed by officers to justify dual arrests in a preferred arrest
      jurisdiction. Content analysis of thought protocols of police officers (n=24) who
      reported they would arrest both parties was undertaken. Officers justified arrest
      of both parties, citing that such was required by law and the desire to force
      both parties to obtain counseling for their relationship. Implications for policy
      development are examined.

PMID- 16456153
TI  - An examination of sexual violence against college women.
AB  - This investigation examined college women's experiences with unwanted sexual
      contact. Participants completed a questionnaire assessing the incidence of
      various types of forced sexual contact the women had experienced since enrolling
      in college. Demographic and situational variables associated with these incidents
      of sexual violence were also obtained. It was observed that since enrolling in
      college, 27% of the sample had experienced unwanted sexual contact ranging from
      kissing and petting to oral, anal, or vaginal intercourse. Type of sexual
      violence, perpetrator characteristics, and racial differences regarding types of
      unwanted sexual contact were examined. The implications of the data are
      discussed.

PMID- 16456154
TI  - Separation and/or divorce sexual assault in rural Ohio: preliminary results of an
      exploratory study.
AB  - A rapidly growing social scientific literature shows that many women are at great
      risk of being killed, beaten, or psychologically abused when they exit or try to
      leave their marital and/or cohabiting partners. However, less than a handful of
      studies have examined male-to-female sexual assaults during and after separation
      or divorce. Furthermore, the bulk of the limited empirical work on this problem
      was done in urban areas. Thus, the main objective of this article is to help fill
      two major research gaps by presenting the preliminary results of an ongoing
      exploratory study of separation and/or divorce sexual assault in rural Ohio.

PMID- 16456155
TI  - Development and pathogenesis of Parelaphostrongylus odocoilei (nematoda:
      protostrongylidae) in experimentally infected thinhorn sheep (Ovis dalli ).
AB  - Recently, the protostrongylid nematode Parelaphostrongylus odocoilei has been
      reported in a new host species, thinhorn sheep (Ovis dalli). For the first time,
      we completed the life cycle of P. odocoilei in three Stone's sheep (O. dalli
      stonei) and two thinhorn hybrids (O. dalli stonei x O. dalli dalli), each
      infected with 200 third-stage larvae from slugs (Deroceras laeve). The prepatent
      period ranged from 68 days to 74 days, and shedding of first-stage larvae (L1)
      peaked at >10,000 L1 per gram of feces between 90 and 110 days postinfection. A
      total of 75, 27, and 14 adult P. odocoilei were recovered from skeletal muscles
      of three Stone's sheep. Starting in the prepatent period, all infected sheep lost
      weight and developed peripheral eosinophilia. At 2 wk before patency, two
      thinhorn hybrids developed neurologic signs (hind end ataxia, loss of conscious
      proprioception, and hyperesthesia) that resolved at patency. Eosinophilic
      pleocytosis and antibody to Parelaphostrongylus spp. were detected in the
      cerebrospinal fluid of the affected sheep, suggesting that the migration route of
      the "muscleworm" P. odocoilei may involve the central nervous system. Twenty days
      after treatment with ivermectin, neurologic signs recurred and larval shedding
      ceased in one infected thinhorn hybrid, whereas multiple treatments transiently
      suppressed but did not eliminate larval shedding in the other. During patency,
      two Stone's sheep with numerous eggs and larvae of P. odocoilei in the lungs died
      of respiratory failure following anesthesia or exertion. Parelaphostrongylus
      odocoilei has widespread geographic distribution, high prevalence, the
      possibility of causing neurologic and respiratory disease, resistance to
      treatment, and may constitute a significant emerging disease risk for thinhorn
      sheep.

PMID- 16456156
TI  - New ruminant hosts and wider geographic range identified for Babesia odocoilei
      (Emerson and Wright 1970).
AB  - Babesia odocoilei was found to infect two previously unknown host species, desert
      bighorn sheep (Ovis canadensis nelsoni) and musk oxen (Ovibos moschatus), both of
      which are members of the family Bovidae. Previously, B. odocoilei has been
      reported in only Cervidae hosts. New geographic regions where B. odocoilei
      infections have not been reported previously include Pennsylvania and New York,
      where fatal babesiosis has occurred in reindeer (Rangifer tarandus tarandus); New
      Hampshire, where elk (Cervus elaphus canadensis) have been affected; and
      California, home of the infected desert bighorn sheep. Infection with B.
      odocoilei in these hosts was confirmed by parasite small subunit ribosomal RNA
      gene sequence analysis. A serosurvey for B. odocoilei antibody activity in New
      Hampshire showed prevalence rates of 100% at two elk farms and 12% at another
      farm. Control of potential vector ticks, Ixodes scapularis, especially when
      translocating livestock, is imperative to prevent outbreaks of babesiosis in
      managed herds of potential host species.

PMID- 16456157
TI  - Exploring the ecologic basis for extreme susceptibility of Pallas' cats
      (Otocolobus manul) to fatal toxoplasmosis.
AB  - Recent efforts by North American zoos to establish a genetically viable captive
      population of Pallas' cats (Otocolobus manul) have been compromised by high
      newborn mortality (approximately 60%), primarily because of toxoplasmosis. The
      basis for this extreme susceptibility to toxoplasmosis is unknown. In the present
      study, the general health status of wild Pallas' cats in Mongolia was evaluated,
      including assessment of basal hematologic parameters and fecal corticoid
      metabolite concentrations. The prevalence of exposure to Toxoplasma gondii in
      Mongolian Pallas' cats, local domestic cats, and prey species also was determined
      based on serology and/or polymerase chain reaction analysis. Biologic samples
      (blood, feces, and/or brain tissue) were obtained from 15 wild Pallas' cats, 15
      domestic cats, and 45 prey animals (rodents and pikas) captured in Mongolia
      during the summers of 2000 and 2001. Comparative data were obtained from nine
      captive Pallas' cats maintained in North American zoos. Based on physical
      examinations, complete blood counts, and blood chemistry analyses, only minor
      differences were observed in the general health status of wild and captive
      Pallas' cats. Fecal cortisol metabolite concentrations did not differ (P > 0.05)
      between populations, indicating that Pallas' cats in captivity and in the wild
      have similar basal adrenocortical activity. A pronounced difference (P < 0.01) in
      seroprevalence to T. gondii was observed between populations. Whereas all captive
      Pallas' cats exhibited elevated immunoglobulin titers (IgG > 2,048) to T. gondii,
      only two of 15 (13%) wild Pallas' cats were seropositive, with both cats having
      lower IgG titers (< 1,024). Furthermore, no evidence of exposure to this parasite
      was found in any of the Mongolian domestic cats or prey species. These findings
      suggest that wild Pallas' cats have minimal opportunity for exposure to T. gondii
      in their natural habitat and, typically, do not become infected with this
      parasite until being brought into captivity. Accordingly, maintenance of a viable
      captive population may require implementing effective strategies to prevent
      exposure of immunologically naive Pallas' cats to T. gondii and to reduce
      parasite transmission between seropositive females and their highly susceptible
      offspring.

PMID- 16456158
TI  - Phylogenetic classification of the frog pathogen Amphibiothecum (Dermosporidium)
      penneri based on small ribosomal subunit sequencing.
AB  - We determined 1,600 base pairs of DNA sequence in the 18S small ribosomal subunit
      from two geographically distinct isolates of Dermosporidium penneri. Maximum
      likelihood and parsimony analysis of these sequences place D. penneri in the
      order Dermocystida of the class Mesomycetozoea. The 18S rRNA sequences from these
      two isolates only differ within a single region of 16 contiguous nucleotides.
      Based on the distant phylogenetic relationship of these organisms to
      Amphibiocystidium ranae and similarity to Sphaerothecum destruens we propose the
      organism be renamed Amphibiothecum penneri.

PMID- 16456160
TI  - Spondylitic changes in long-finned pilot whales (Globicephala melas) stranded on
      Cape Cod, Massachusetts, USA, between 1982 and 2000.
AB  - The primary bone pathology diagnoses recognized in cetacea are osteomyelitis and
      spondylosis deformans. In this study, we determined the prevalence, type, and
      severity of vertebral pathology in 52 pilot whales, a mass stranding species that
      stranded on Cape Cod, Massachusetts, between 1982 and 2000. Eleven whales (21%)
      had hyperostosis and ossification of tendon insertion points on and between
      vertebrae, chevron bones, and costovertebral joints, with multiple fused blocks
      of vertebrae. These lesions are typical of a group of interrelated diseases
      described in humans as spondyloarthropathies, specifically ankylosing
      spondylitis, which has not been fully described in cetacea. In severe cases,
      ankylosing spondylitis in humans can inhibit mobility. If the lesions described
      here negatively affect the overall health of the whale, these lesions may be a
      contributing factor in stranding of this highly sociable species.

PMID- 16456159
TI  - Pathology and proposed pathophysiology of diclofenac poisoning in free-living and
      experimentally exposed oriental white-backed vultures (Gyps bengalensis).
AB  - Oriental white-backed vultures (Gyps bengalensis; OWBVs) died of renal failure
      when they ingested diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), in
      tissues of domestic livestock. Acute necrosis of proximal convoluted tubules in
      these vultures was severe. Glomeruli, distal convoluted tubules, and collecting
      tubules were relatively spared in the vultures that had early lesions. In most
      vultures, however, lesions became extensive with large urate aggregates obscuring
      renal architecture. Inflammation was minimal. Extensive urate precipitation on
      the surface and within organ parenchyma (visceral gout) was consistently found in
      vultures with renal failure. Very little is known about the physiologic effect of
      NSAIDs in birds. Research in mammals has shown that diclofenac inhibits formation
      of prostaglandins. We propose that the mechanism by which diclofenac induces
      renal failure in the OWBV is through the inhibition of the modulating effect of
      prostaglandin on angiotensin II-mediated adrenergic stimulation. Renal portal
      valves open in response to adrenergic stimulation, redirecting portal blood to
      the caudal vena cava and bypassing the kidney. If diclofenac removes a modulating
      effect of prostaglandins on the renal portal valves, indiscriminant activation of
      these valves would redirect the primary nutrient blood supply away from the renal
      cortex. Resulting ischemic necrosis of the cortical proximal convoluted tubules
      would be consistent with our histologic findings in these OWBVs.

PMID- 16456161
TI  - Prevalence of anomalies in the appendicular skeleton of a fossorial rodent
      population.
AB  - The prevalence of macroscopic bone anomalies in the appendicular skeleton of wild
      rodents and, particularly, fossorial species is not well known. We examined 8,257
      bones corresponding to 564 collection specimens (249 males and 315 females) of a
      fossorial form of water vole (Arvicola terrestris monticola). Animals were
      obtained monthly from July 1983 to December 1984 in the Aran Valley (Pyrenees).
      Most macroscopic anomalies were healed fractures or exostoses. The prevalence of
      anomalies was not significantly different between males and females but was
      clearly higher in adults than in juveniles and subadults. The frequency of
      alterations in the thoracic limb long bones was significantly higher than that in
      the pelvic counterparts. Aggressive intraspecific interactions and biomechanical
      factors related to burrowing may be associated with these differences. In
      females, remodeling of the innominate shape because of pregnancy and parturition
      could enhance fractures and exostoses in this structure.

PMID- 16456162
TI  - Prevalences of zoonotic bacteria among seabirds in rehabilitation centers along
      the Pacific Coast of California and Washington, USA.
AB  - Many seabirds are rehabilitated annually by wildlife rehabilitation centers along
      the Pacific Coast, USA. Although various strains of zoonotic bacteria have been
      isolated from seabirds, risks to rehabilitators at these centers have not been
      well documented. From November 2001 through January 2003, we determined the
      prevalence of detectable enteric fauna by isolation and characterization of Gram
      negative bacteria from cloacal swabs taken from 26 common murres (Uria aalge), 49
      gulls (Larus spp.), and 14 other seabirds treated by rehabilitators in California
      and Washington (USA). At least 25 bacterial species were identified, including
      multiple strains of Escherichia coli, as well as Enterobacter cloacae,
      Citrobacter freundii, and Klebsiella pneumoniae. Antibiotic resistance was found
      in 13 of 19 bacterial isolates tested, including E. coli, K. pneumoniae,
      Acinetobacter baumanii, and Pseudomonas aeruginosa. Potential transfer of these
      bacteria poses a risk to wildlife rehabilitators and to seabirds in these
      centers, as well as to free-ranging birds.

PMID- 16456163
TI  - Poxvirus infection of Steller sea lions (Eumetopias jubatus) in Alaska.
AB  - Lesions suggestive of poxvirus infection were observed in two Steller sea lions
      (Eumetopias jubatus) in Alaska during live capture-and-release studies during
      2000 and 2001. Both of these animals, female pups in poor body condition, were
      from Prince William Sound; this population is part of the declining western
      stock. Umbilicated, typically ulcerated dermal nodules were present, primarily on
      the fore flippers in one case, and over most of the body in the second case.
      Histologically, there were discrete masses in the superficial dermis composed of
      epithelial cells, some of which contained eosinophilic intracytoplasmic inclusion
      bodies. Negative staining of skin biopsy homogenates demonstrated the presence of
      orthopoxvirus-like particles. Total DNA extracted from skin biopsies were
      analyzed by polymerase chain reaction (PCR) using primers that targeted the DNA
      polymerase and DNA topoisomerase genes. These primers directed the amplification
      of fragments 543 base pairs (bp) and 344 bp, respectively, whose deduced amino
      acid sequences indicated the presence of a novel poxvirus within the
      Chordopoxvirinae subfamily. Comparison of these amino acid sequences with
      homologous sequences from members of the Chordopoxvirinae indicated highest
      identity with orthopoxviruses.

PMID- 16456164
TI  - Flying foxes as carriers of pathogenic Leptospira species.
AB  - Recent serologic studies have identified flying foxes (Pteropus spp.) as carriers
      of leptospirosis; however, little is known about the role of flying foxes as
      carriers of pathogenic Leptospira spp. To determine if Australian Pteropus spp.
      are carriers of pathogenic Leptospira spp., TaqMan real-time polymerase chain
      reaction (PCR) was used to detect leptospiral DNA in kidney and urine specimens
      from four species of flying fox, including the spectacled flying fox (Pteropus
      conspicillatus), black flying fox (Pteropus alecto), grey-headed flying fox
      (Pteropus poliocephalus), and little red flying fox (Pteropus scapulatus). Of the
      173 kidney samples tested, 19 (11%) were positive for leptospiral DNA. Positive
      individuals were detected in all four species; significant differences in
      prevalence were not detected between species, between species within the same
      geographic area, or between geographically separated samples from the same
      species. Of the 46 urine samples tested, 18 (39%) tested positive by PCR,
      confirming that flying foxes shed leptospires into the environment. The detection
      of leptospiral DNA in the kidneys and urine of flying foxes suggests that flying
      foxes are carriers of pathogenic Leptospira spp. No evidence collected in the
      present study, however, suggests that flying foxes pose a significant risk of
      leptospirosis to the wider community or that humans who are in regular, close
      contact with flying foxes are at risk for leptospirosis.

PMID- 16456165
TI  - Evaluation of remotely delivered leuprolide acetate as a contraceptive agent in
      female elk (Cervus elaphus nelsoni).
AB  - Practical application of fertility control technology in free-ranging wild
      ungulates often requires remote delivery of the contraceptive agent. The
      objective of this investigation was to evaluate the potential of remote delivery
      of leuprolide acetate for suppressing fertility in female elk (Cervus elaphus
      nelsoni). Fifteen captive adult female elk were randomly allocated to one of
      three experimental groups. Six elk were injected intramuscularly with a dart
      containing leuprolide, and the remaining nine elk received the same formulation
      without leuprolide. We determined pregnancy rates, suppression of luteinizing
      hormone (LH) and progesterone concentrations, and reversibility of treatments
      during 1 August 2002 to 3 September 2003. Leuprolide formulation caused a
      decrease in concentrations of LH and progesterone, temporary suppression of
      ovulation and steroidogenesis, and effective contraception (100%) for one
      breeding season. These results extend the practical application of this
      contraceptive agent to include dart delivery, where in the absence of such
      technology, wild elk must first be captured and restrained before treatment.

PMID- 16456166
TI  - Assessment of newcastle disease vaccination of houbara bustard breeders
      (Chlamydotis undulata undulata).
AB  - The houbara bustard (Chlamydotis undulata undulata) is endangered in North
      Africa. Through a captive-breeding program established in Morocco by The Emirates
      Center for Wildlife Propagation, wild populations are being supplemented by the
      releasing of captive-reared birds. Newcastle disease, which is caused by
      Newcastle disease virus (NDV; Avian paramyxovirus type 1), can infect houbara
      bustards and is a significant threat through contact with backyard poultry and
      possibly wild birds. Three vaccination schedules for Newcastle disease were
      evaluated by serologic monitoring to assess the efficiency and safety of various
      types of vaccines (live vs. inactivated), vaccine strains (Hitchner B1 and Clone
      30), and administration routes (intranasal vs. injection). We evaluated antibody
      titers in 211 adult houbara bustards for 10 mo. Antibody titers to NDV in both
      sera and egg yolks were monitored by hemagglutination inhibition test. The
      inactivated vaccine provided a high, homogeneous, and durable serologic response
      in breeders; titers were higher than log2 11 after 4 wk and remained higher than
      log2 7 after 10 mo. The response to the two live vaccines was similar, and
      antibody titers did not exceed log2 6 at sero-conversion. Maternally derived
      antibodies were efficiently transmitted in vitellus, further confirming that
      offspring of females hyperimmunized with the inactivated vaccine received high
      titers of maternal antibodies.

PMID- 16456167
TI  - Contagious mucocutaneous dermatitis of the mountain hare (Lepus timidus):
      pathology and cause.
AB  - Contagious mucocutaneous dermatitis is a frequently encountered disease of
      mountain hares (Lepidus timidus) in Finland. We describe the histopathologic
      changes and propose an etiologic cause for this disorder. Fifty-three cases
      collected during 1982-2000 were examined histologically. Transmission electron
      microscopy was performed in one case. In fully developed lesions, keratinocytes
      in epidermis and follicular infundibula were swollen and contained large
      eosinophilic intracytoplasmic inclusion bodies with marked reticular and
      ballooning degeneration. In later stages, there was marked necrosis and
      ulceration with severe pyogranulomatous and suppurative inflammation. At this
      stage, no viral inclusions were detectable, but secondary Staphylococcus warnerii
      infection was present in most cases. In late lesions, there was dermal fibrosis
      with epidermal hyperplasia. No spiral-shaped bacteria suggesting treponematosis
      were detected at any stage. Ultrastructurally, swollen epidermal and follicle
      infundibular cells contained round intracytoplasmic inclusion bodies with a
      myriad of virions typical of poxvirus with a biconcave nucleocapsid core, two
      lateral bodies, and a clearly discernible outer lipoprotein capsule. The findings
      suggest that contagious mucocutaneous dermatitis in mountain hares is a viral
      disease caused by a poxvirus. The disease is often complicated by secondary
      bacterial infection, most commonly S. warneri.

PMID- 16456168
TI  - European brown hare syndrome in wild European brown hares from Greece.
AB  - From 1999 to mid-2003, 97 European brown hares (Lepus europaeus) found dead
      throughout Greece were examined by necropsy, histopathology, and reverse
      transcription polymerase chain reaction (RT-PCR) for the presence of European
      brown hare syndrome (EBHS) and EBHS virus (EBHSV), respectively. Hare losses were
      sporadic, starting in the cold season and lasting for many months (December to
      May). The most prominent gross lesions were observed in the liver and included
      swelling and discoloration; congestion and hemorrhages were present mainly in
      lungs and tracheal mucosa. Necropsy findings were suggestive of EBHS, which was
      confirmed by histopathology and RT-PCR. This study documents, for the first time,
      EBHS in Greece.

PMID- 16456169
TI  - Serologic survey of select infectious diseases in coyotes and raccoons in
      Nebraska.
AB  - To obtain data about select zoonotic and other infectious diseases in free
      ranging predators in five ecoregions in Nebraska, sera were collected from 67
      coyotes (Canis latrans) and 63 raccoons (Procyon lotor) from November 2002
      through January 2003. For coyotes, antibodies were detected against canine
      distemper virus (CDV, 61%), Francisella tularensis (32%), Rickettsia rickettsi
      (13%), and flaviviruses (48%). None of the coyote sera had antibodies to Borrelia
      burgdorferi, Brucella canis, or six serovars of Leptospira interrogans. Because
      serologic cross-reactivity exists among flaviviruses, 14 sera from flavivirus
      positive coyotes were also tested for St. Louis encephalitis virus (SLE)
      antibodies and two (14%) were positive, suggesting that up to 48% of coyotes
      tested had antibodies against West Nile virus (WNV). For raccoons, antibodies
      were detected against CDV (33%), F. tularensis (38%), and three serovars of L.
      interrogans (11%).

PMID- 16456170
TI  - A serologic survey for antibodies to three canine viruses in wolverines (Gulo
      gulo) from the Brooks Range, Alaska.
AB  - Canine distemper virus (CDV), canine parvovirus type 2 (CPV-2), and canine
      adenovirus type 1 (CAV-1) are pathogens that are typically associated with canids
      but may cause serious disease in a wide range of other carnivores. From 1998 to
      2002, serum samples from 64 wolverines (Gulo gulo) from the Brooks Range, Alaska,
      were tested for antibodies to CDV, CPV-2, and canine adenovirus (CAV). Four
      animals tested positive for antibodies to CDV (7%), one for antibodies to CPV-2
      (2%), and none for antibodies to CAV. These are similar to antibody prevalence
      estimates for other large and medium carnivores in North America.

PMID- 16456171
TI  - Prevalence of antibodies to porcine parvovirus in wild boars (Sus scrofa) in
      Croatia.
AB  - Serologic evidence of exposure to porcine parvovirus (PPV) in the wild boar (Sus
      scrofa) in Croatia was investigated. Serum samples from 219 wild boars captured
      during 2003 from 12 different locations in the Republic of Croatia were tested by
      using a commercial enzyme-linked immunoassay (ELISA) and a hemagglutination
      inhibition (HI) test. Antibodies to PPV were detected in 91 (41.6%) of tested
      samples and positive results were detected in wild boar from all sample
      locations. Adults had a significantly higher prevalence (70%) than juveniles
      (31%; P < 0.01). Our results indicate that wild boar populations throughout the
      Republic of Croatia are exposed to PPV.

PMID- 16456172
TI  - Presence of antibodies against Aujeszky's disease virus in wild boar (Sus scrofa)
      in Slovenia.
AB  - Serum samples from 427 hunter-killed wild boar (Sus scrofa) from Slovenia were
      tested for antibodies to Aujeszky's disease virus (ADV). Samples were collected
      throughout Slovenia and corresponded to 6.2% of the total harvest. Antibodies
      against ADV were detected in 111 sera (26%) using a commercial enzyme-linked
      immunosorbent assay (ELISA). Antibody prevalence increased significantly with
      age. This report describes the first evidence of ADV infection in wild boar
      populations in Slovenia.

PMID- 16456173
TI  - Herpesvirus infection in woodland caribou in Alberta, Canada.
AB  - Sera and genital swabs collected from 121 adult woodland caribou (Rangifer
      tarandus caribou) in five subpopulations in northern Alberta, Canada, between
      December 1997 and October 1999, were examined for evidence of infection with
      herpesviruses or pestiviruses. No virus was isolated from sera or swabs, and no
      antibodies against bovine viral diarrhea virus were detected. However, 63 (52%)
      of the 121 animals had neutralizing antibody titers against bovine herpesvirus 1.
      There was sufficient serum from 37 of the 121 caribou to allow parallel testing
      for antibodies against a new alphaherpesvirus isolated from an elk (Cervus
      elaphus nelsoni), and 20 animals had antibodies against this virus. Paired sera
      collected 11 mo apart from 14 caribou showed seroconversion in seven animals,
      indicating that an active herpesvirus infection was present. Virus neutralization
      data suggest that these caribou are infected with a distinct alphaherpesvirus.

PMID- 16456174
TI  - Theileriosis in a white-tailed deer (Odocoileus virginianus) fawn.
AB  - A white-tailed deer (Odocoileus virginianus) fawn was collected in Missouri (USA)
      and submitted for diagnostic evaluation. Necropsy and histologic examination
      revealed severe Amblyomma americanum infestation, pronounced icterus, and marked
      hemosiderin deposition in the liver and spleen. Whole blood evaluation revealed a
      normocytic normochromic anemia and a piroplasm parasitemia of approximately 70%.
      The piroplasm was identified as Theileria cervi by polymerase chain reaction and
      sequencing of the V4 variable region of the 18S rRNA gene from a paraffin
      embedded section of lung. Although T. cervi parasitemias have been commonly
      reported in healthy white-tailed deer, the severe parasitemia in this fawn may
      have contributed to overt clinical disease, perhaps as part of a combined
      malnutrition and parasitemia syndrome.

PMID- 16456175
TI  - First report of an intraerythrocytic small piroplasm in wild Iberian lynx (Lynx
      pardinus).
AB  - A wild injured Iberian lynx (Lynx pardinus) was taken from the Sierra Morena
      population. During the health check small intraerythrocytic piroplasms,
      morphologically indistinguishable from other feline piroplasms, were observed in
      Wright-Giemsa-stained blood films. Amplification by polymerase chain reaction of
      a portion of the 18S nuclear small subunit (NSS) rRNA gene and sequencing
      revealed similarity of the unknown organism with sequences obtained from Pallas's
      cat from Mongolia and from a domestic cat in Spain. In a retrospective (1993
      2003) study of 50 Iberian lynx tissue samples, no amplifications of the 18S NSS
      rRNA gene of the organism were obtained. This is the first report of a naturally
      occurring erythroparasitemia in the Iberian lynx and the first documented case of
      naturally occurring piroplasm infection in a free-ranging felid from Europe.

PMID- 16456176
TI  - Angiostrongylus vasorum infection in a coyote (Canis latrans) from Newfoundland
      and Labrador, Canada.
AB  - Tissue samples and feces were collected from a dead, adult female coyote (Canis
      latrans) found at the side of the road in late March 2003 in the Avalon Peninsula
      region of Newfoundland, Canada. The coyote apparently died of vehicular-related
      trauma. Samples of lung, brain, heart, liver, and kidney were fixed in formalin
      and submitted for histologic examination. The entire remaining lung and heart
      also were submitted for examination. The coyote was diagnosed with moderate,
      multifocal, granulomatous interstitial pneumonia with eosinophilic vasculitis and
      many intralesional nematode eggs, larvae, and occasional intravascular adult
      worms. Adult nematodes recovered from the pulmonary arteries were identified as
      Angiostrongylus vasorum. Small foci of granulomatous inflammation, often
      containing nematode eggs and larvae, were scattered in the brain and kidney. To
      our knowledge, this is the first report of A. vasorum infection in a coyote from
      the only endemic area of infection in North America.

PMID- 16456177
TI  - Tonsillar biopsy test for chronic wasting disease: Two sampling approaches in
      mule deer and white-tailed deer.
AB  - Preclinical antemortem testing of deer (Odocoileus spp.) for chronic wasting
      disease (CWD) can be important for determining prevalence rates and removing
      infected individuals from wild populations. Because samples with high numbers of
      tonsillar follicles are likely to provide earlier detection of CWD than samples
      with fewer follicles, the method of obtaining follicular samples may be critical
      when investigating disease prevalence. Between January 2003 and January 2005,
      white-tailed deer (O. virginianus) in southeast and southwest Minnesota and white
      tailed and mule deer (O. hemionus) in Wind Cave National Park, South Dakota, were
      sampled using dorso-lateral and ventral-medial approaches for collecting
      tonsillar follicles. We obtained significantly more follicles using a dorso
      lateral (median number of follicles = 19) rather than a ventral-medial (median
      number of follicles = 5.5) approach. No differences were observed in collection
      of tonsillar follicles that were related to sex, age class, or species of deer.
      We recommend the dorso-lateral approach for assessing CWD prevalence in deer
      populations.

PMID- 16456178
TI  - Fallot's tetralogy in a European brown bear (Ursus arctos).
AB  - A congenital heart malformation was diagnosed in a free-ranging adult female
      European brown bear (Ursus arctos) found dead due to intraspecific violence. At
      necropsy, the heart had all four features of Fallot's tetralogy. No further
      malformations were identified in the animal, which was of normal size and weight
      for its age, in normal body condition, and had probably borne young. The heart
      condition was considered to have contributed to death during an attack by another
      bear.

PMID- 16456179
TI  - Suspected secondary thiafentanil intoxication in a captive mountain lion (Puma
      concolor).
AB  - Inadvertent ingestion of thiafentanil oxalate by a captive adult female mountain
      lion (Puma concolor) caused a prolonged clinical syndrome that included sedation
      and depression, muscle tension, and myopathy that was incompletely antagonized by
      naltrexone HCl. A serum chemistry profile revealed markedly elevated creatinine
      phosphokinase (CK; 490,450 IU/l), alanine aminotransferase (ALT; 1,896 IU/l), and
      aspartate aminotransferase (AST; 4,321 IU/l) 2 days after onset. The affected
      animal's condition gradually improved over the next 15 days in response to
      supportive therapy that included diazepam (5 mg as needed), Normasol R (3 l/day),
      dexamethasone (tapering dose starting at 1 mg/kg), and ketoprofen (1 mg/kg). She
      eventually recovered completely. Based on these observations, carcasses of
      animals immobilized with thiafentanil should be marked and disposed of properly
      to preclude opportunities for secondary exposure and potential intoxication in
      scavenging species. In addition, caution is advised when using thiafentanil in
      animals that could be preyed upon before full metabolism of the drug.

PMID- 16456180
TI  - Malignant lymphoma in a West Indian manatee (Trichechus manatus).
AB  - We identified a malignant lymphoma infiltrating the lung, liver, kidney,
      mesenteric lymph nodes, and eye as the cause of death in a male West Indian
      manatee (Trichechus manatus). Diagnosis was based on gross, histopathologic, and
      immunohistochemical studies. Tissue samples from ten organs were included in a
      tissue microarray and sections from this array were subjected to
      immunohistochemical staining. The cytoplasm of the neoplastic lymphocytes
      identified in six organs was positive for CD3, a marker for T-cell
      differentiation. The neoplastic cells were negative for CD79alpha, a marker for B
      cell differentiation. The cause of this neoplasm was not determined. This is the
      first report of malignant lymphoma in the mammal order Sirenia.

PMID- 16456181
TI  - Mycoplasmosis in free-ranging desert tortoises in Utah and Arizona.
AB  - Upper respiratory tract disease (URTD) has been associated with major losses of
      free-ranging desert tortoises (Gopherus agassizii) in the southwestern United
      States. This prompted a clinical examination of 63 free-ranging desert tortoises
      for signs of URTD and sampling for Mycoplasma agassizii, the causative agent of
      URTD. Tortoises were sampled from three sites in the eastern Mojave Desert (1992
      93), and from three sites in the Sonoran Desert (1992-94). Plasma samples were
      tested for antibodies to M. agassizii using an enzyme-linked immunosorbent assay
      (ELISA). Nasal aspirate samples from 12 Sonoran tortoises were tested using
      polymerase chain reaction (PCR) test directed at the 16S rRNA gene of M.
      agassizii. Nasal aspirate samples from all tortoises were cultured for M.
      agassizii. In the Mojave Desert, nine tortoises had clinical signs of URTD and
      eight were seropositive for M. agassizii. In the Sonoran Desert, there were no
      clinical signs of URTD, but two tortoises were seropositive, and two tortoises
      had positive PCR results.

PMID- 16456182
TI  - Effects of sex, age, body mass, and capturing method on hematologic values of
      brown bears in Croatia.
AB  - Effects of various intrinsic and extrinsic factors on 17 hematologic values from
      56 brown bears (Ursus arctos) sampled in Croatia from 1981 to 2005 were
      evaluated. Differences between female and male bears were detected for number of
      erythrocytes, sedimentation rate after 30 min, and number of leukocytes and
      segmented neutrophils. Significant differences between free-living vs. captive
      and snared vs. not snared bears were detected for the same three parameters:
      leukocytes, segmented neutrophils, and eosinophils. It was concluded that the
      physical exertion of bears snared by leg, rather than their free-living status,
      influenced differences of results among these groups. The obtained mean values
      are useful reference values for the species.

PMID- 16456183
TI  - Regulation of mucin genes in chronic inflammatory airway diseases.
AB  - In this review, we summarize work over the past 15 years on mucin gene expression
      and regulation in the lung, as well as how mucin gene expression is altered in
      chronic lung diseases. This field owes a great debt to Carol Basbaum for her
      pioneering work in dissecting signaling pathways regulating mucin gene expression
      and for her tremendous energy in promoting the importance of understanding the
      basic pathogenic mechanisms that drive mucus overproduction in cystic fibrosis,
      chronic obstructive pulmonary disease, and asthma.

PMID- 16456184
TI  - Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas
      aeruginosa.
AB  - Surfactant protein (SP)-A and SP-D, members of the collectin family, are involved
      in innate host defenses against various bacterial and viral pathogens. In this
      study, we asked whether SP-A and SP-D enhance clearance of a nonmucoid strain of
      Pseudomonas aeruginosa from the lungs. We infected mice deficient in SP-A (SP-A-/
      ), SP-D (SP-D-/-) and both pulmonary collectins (SP-AD-/-) by intratracheal
      administration of P. aeruginosa. Six hours after infection, bacterial counts were
      significantly higher in SP-A-/-, SP-D-/-, and SP-AD-/- compared with wild-type
      (WT) mice. Forty-eight hours after infection, bacterial counts were significantly
      higher in SP-A-/- mice compared with WT mice and in SP-AD-/- mice compared with
      WT, SP-A-/-, and SP-D-/- mice. Phagocytosis of the bacteria by alveolar
      macrophages was decreased in SP-A-/- and SP-D-/- mice. Levels of macrophage
      inflammatory peptide-2 and IL-6 were more elevated in the lungs of SP-D and SP-AD
      /- mice compared with WT mice. There was more infiltration by neutrophils in the
      lungs of SP-D-/- compared with WT and SP-A-/- mice 48 h after infection. This
      study shows that SP-A and SP-D enhance pulmonary clearance of P. aeruginosa by
      stimulating phagocytosis by alveolar macrophages and by modulating the
      inflammatory response in the lungs. These findings also show that the functions
      of SP-A and SP-D are not completely redundant in vivo.

PMID- 16456185
TI  - Regulation of the ClC-2 lung epithelial chloride channel by glycosylation of SP1.
AB  - Chloride channel-2 (ClC-2) is a pH- and voltage-activated chloride channel that
      is highly expressed in mammalian fetal airway epithelia during the period of
      maximal fluid secretion. A high level of luminal ClC-2 protein expression is
      maintained by the SP1 transcription factor until SP1 and ClC-2 decline rapidly at
      birth. Using fetal (preII-19) and adult (L2) rat lung Type 2 cell lines, we
      demonstrate that the active higher-molecular-weight 105-kD isoform of SP1 is
      phosphorylated and glycosylated. Exposure of either cell line to high-dose
      glutamine is sufficient to induce glycosylation of SP1 and to induce and maintain
      ClC-2. Exposure to tunicamycin to inhibit SP1 glycosylation reduces ClC-2
      expression. We also demonstrate that in vivo ClC-2 expression is similarly
      regulated. SP1 from 6-wk-old murine lung (high ClC-2 expression) is
      hyperphosphorylated and hyperglycosylated compared with SP1 from 16-wk-old lung
      (low ClC-2 expression). Our results support the hypothesis that glycosylation of
      SP1 produces the 105-kD isoform of SP1 and is involved in regulating ClC-2 gene
      expression.

PMID- 16456186
TI  - Retinoic acid inhibits airway smooth muscle cell migration.
AB  - Airway remodeling in chronic asthma is characterized by increased smooth muscle
      mass that is associated with the reduction of the bronchial lumen as well as
      airway hyperresponsiveness. The development of agents that inhibit smooth muscle
      growth is therefore of interest for therapy to prevent asthma-associated airway
      remodeling. All-trans retinoic acid (ATRA) suppresses growth of vascular smooth
      muscle cells (SMCs) from the systemic and pulmonary circulation. The present
      study investigated the effects of ATRA on human bronchial (airway) SMCs. Human
      bronchial SMCs were found to express mRNAs for retinoic acid receptor (RAR)
      alpha, -beta, -gamma, and retinoid X receptor (RXR)-alpha, -beta, but not RXR
      gamma. Although ATRA was not effective in inhibiting proliferation or in inducing
      apoptosis in airway SMCs, we found that ATRA (0.2-2 microM) inhibited the SMC
      migration in response to platelet-derived growth factor (PDGF), as determined in
      a modified Boyden chamber assay. Both RAR and RXR agonists also blocked PDGF
      induced airway SMC migration. ATRA also inhibited PDGF-induced actin
      reorganization associated with migration. PDGF-induced actin reorganization and
      migration were blocked by inhibitors of phosphatidylinositol 3 kinase (PI3K) and
      Akt. However, migration was blocked by inhibitors of the MEK/ERK pathway, with no
      effect on cytoskeletal reorganization. ATRA suppressed PDGF-induced Akt
      activation without influencing ERK activation. RAR was found to form protein
      protein interactions with the p85 PI3K subunit. These results suggest that
      retinoic acid inhibits airway SMC migration through the modulation of the
      PI3K/Akt pathway.

PMID- 16456187
TI  - Eosinophil trans-basement membrane migration induced by interleukin-8 and
      neutrophils.
AB  - Neutrophilic inflammation observed with severe asthma is often associated with
      interleukin-8 (IL-8). Neutrophils can secrete a variety of mediators that may
      augment the migration of eosinophils. We have reported a positive correlation
      between the concentrations of neutrophils and eosinophils in sputum from subjects
      with severe asthma, suggesting a possible role of neutrophils in regulating
      eosinophilic inflammation. The aim of this study was to investigate whether
      neutrophils stimulated with IL-8 modify the trans-basement membrane migration
      (TBM) of eosinophils. Eosinophils and neutrophils were isolated from peripheral
      blood drawn from healthy donors or subjects with mild asthma. The TBM of
      eosinophils in response to IL-8 was evaluated in the presence or absence of
      neutrophils using the chambers with a Matrigel-coated transwell insert. Neither
      IL-8 alone nor the presence of neutrophils alone induced the TBM of eosinophils.
      However, when eosinophils were coincubated with neutrophils and stimulated with
      IL-8, the TBM of eosinophils was significantly augmented. This augmented TBM of
      eosinophils was inhibited by a matrix metalloproteinase-9 inhibitor, a
      leukotriene B4 receptor antagonist, platelet-activating factor antagonists, or an
      anti-TNF-alpha monoclonal antibodies. These results suggest that neutrophils
      migrated in response to IL-8 may lead eosinophils to accumulate in the airways of
      asthma and possibly aggravate this disease.

PMID- 16456189
TI  - Regulation of skeletal muscle mitochondrial content during aging.
AB  - Mitochondrial content of skeletal muscle varies among fiber types, and changes in
      complex ways during aging. We evaluated the regulatory origins of differences in
      mitochondrial content among muscles of varied fiber type in F344xBNF1 rats, and
      how these regulatory patterns are altered with aging. In adult (12 month) animals
      we found that units citrate synthase (CS)/g tissue, a marker for mitochondrial
      content, varied approximately 3-fold among 10 skeletal muscles. Stoichiometric
      relationships between CS and isocitrate dehydrogenase, aconitase, and cytochrome
      c oxidase were generally preserved across fiber types. Among the 10 muscles of
      adult rats, CS content correlated with nuclear content (R2= 0.36). Muscles
      differed widely in CS messenger RNA (mRNA)/DNA (an index of variation in
      transcriptional regulations) and units CS/CS mRNA (an index of variation in
      posttranscriptional regulations). All muscles of aged rats (35 months) showed an
      increase in mg DNA/g, suggestive of atrophy. Age-dependent declines in units
      CS/DNA were accompanied by reductions in CS mRNA/DNA and/or units CS/CS mRNA,
      depending on muscle fiber type. Thus, declines in units CS/DNA with age appeared
      to be due to transcriptional as well as translational variations. Differences in
      mitochondrial content among muscle fiber types and age groups may arise from
      variations in nuclear content and posttranscriptional processes, as well as
      transcriptional regulation.

PMID- 16456188
TI  - Eosinophil-mediated cholinergic nerve remodeling.
AB  - Eosinophils are observed to localize to cholinergic nerves in a variety of
      inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis,
      and inflammatory bowel disease, where they are also responsible for the induction
      of cell signaling. We hypothesized that a consequence of eosinophil localization
      to cholinergic nerves would involve a neural remodeling process. Eosinophil co
      culture with cholinergic IMR32 cells led to increased expression of the M2
      muscarinic receptor, with this induction being mediated via an adhesion-dependent
      release of eosinophil proteins, including major basic protein and nerve growth
      factor. Studies on the promoter sequence of the M2 receptor indicated that this
      induction was initiated at a transcription start site 145 kb upstream of the gene
      coding region. This promoter site contains binding sites for a variety of
      transcription factors including SP1, AP1, and AP2. Eosinophils also induced the
      expression of several cholinergic genes involved in the synthesis, storage, and
      metabolism of acetylcholine, including the enzymes choline acetyltransferase,
      vesicular acetylcholine transferase, and acetylcholinesterase. The observed
      eosinophil-induced changes in enzyme content were associated with a reduction in
      intracellular neural acetylcholine but an increase in choline content, suggesting
      increased acetylcholine turnover and a reduction in acetylcholinesterase
      activity, in turn suggesting reduced catabolism of acetylcholine. Together these
      data suggest that eosinophil localization to cholinergic nerves induces neural
      remodeling, promoting a cholinergic phenotype.

PMID- 16456190
TI  - Caloric restriction and aging: controversial issues.
AB  - It has long been held that food restriction extends the life span of rodents and
      other species by decreasing caloric intake and slowing the rate of aging. Recent
      findings challenge these concepts. This review assesses these controversial
      issues. The conclusion is that caloric restriction underlies the life extension
      of rats, but not of Drosophila. Mortality characteristics show that food
      restriction slows the rate of aging of rats and, in some studies, of mice.
      However, in other mouse studies and in Drosophila, mortality characteristics have
      been interpreted as indicating that it delays the start but does not slow the
      rate of aging; the author believes that this interpretation is faulty. These
      differences in mortality responses to food restriction provide a potentially
      powerful tool for uncovering basic mechanisms underlying its life-prolonging
      action. A hypothesis is presented for use in the search for these mechanisms.

PMID- 16456191
TI  - Identification of valid housekeeping genes and antioxidant enzyme gene expression
      change in the aging rat liver.
AB  - Valid housekeeping genes (HKG) are a prerequisite for accurate gene
      quantification. We performed real-time reverse transcription-polymerase chain
      reaction to investigate the gene expression of five commonly used HKGs (beta
      actin, glyceraldehyde-3-phosphate dehydrogenase [GAPDH], ubiquitin C [UBC],
      hypoxanthine phosphoribosyl-transferase [HPRT], and cyclophilin A [CYPa]) and
      antioxidant enzymes in the liver of young and old male Fischer rats. A wide
      variation in HKG expression existed during the aging process, and HPRT was
      identified as the most stable HKG in rat liver aging. When Cu/Zn-superoxide
      dismutase gene expression was normalized to HPRT, there was no detectable
      difference between young and old rats; however, a significant difference was seen
      when it was normalized to UBC. The variation of UBC caused the misinterpretation
      of Cu/Zn-superoxide dismutase expression. Catalase expression was significantly
      decreased, whereas glutathione peroxidase expression was not altered with age. We
      demonstrated that HPRT was an appropriate HKG, validation of HKGs was vital for
      accurate quantification, and decreased catalase expression might be involved in
      the decline of antioxidant defenses during rat liver aging.

PMID- 16456192
TI  - Growth hormone replacement attenuates diastolic dysfunction and cardiac
      angiotensin II expression in senescent rats.
AB  - We tested the hypothesis that long-term growth hormone (GH) replacement in aged
      rats would preserve diastolic function and attenuate left ventricular remodeling
      associated with normal aging. Male Brown Norway x F344 rats were randomized to
      receive twice daily injections of porcine GH (200 microg/injection, subcutaneous)
      or saline from 24 to 30 months of age. Adult rats (6- to 9-months old) received
      saline injections throughout the study. Thirty-month-old, saline-treated rats
      exhibited low levels of insulin-like growth factor 1 (IGF-1), impaired diastolic
      left ventricular filling (Doppler), increased cardiac angiotensin II (Ang II),
      reduced plasma Ang II, and increased cardiac collagen. GH administration in old
      rats restored IGF-1 and diastolic indices to values comparable to those of
      adults. These effects were associated with reduced cardiac Ang II and
      attenuations in cardiac collagen. Age-related decreases in GH and IGF-1 may
      contribute to the decline in diastolic function of aging, in part through
      alterations in renin-angiotensin system-mediated ventricular remodeling.

PMID- 16456193
TI  - The effect of dietary restriction on mitochondrial protein density and flight
      muscle mitochondrial morphology in Drosophila.
AB  - Dietary restriction (DR) extends life span in diverse organisms and may do so by
      attenuating production of mitochondrial reactive oxygen species (ROS). However,
      measurements of ROS production from isolated mitochondria of organisms subjected
      to DR have produced inconsistent results. In the fruit fly Drosophila, DR does
      not reduce production of ROS from isolated mitochondria. In this study, we used
      Drosophila to test whether DR lowered mitochondrial density. We assessed
      mitochondrial densities of flies on DR and Control diets using (a) the activities
      of mitochondrial enzymes and (b) electron microscopy. Both methods showed no
      overall effect of DR on mitochondrial density; however, mitochondrial enzyme
      activities and morphology differed significantly between DR and Control flies. We
      concluded that life-span extension by DR in Drosophila is not mediated through a
      reduction in mitochondrial density. If DR in Drosophila extends life span by
      reducing ROS production, then it does so through mechanisms that operate only in
      vivo.

PMID- 16456194
TI  - Do geriatric interventions reduce emergency department visits? A systematic
      review.
AB  - BACKGROUND: Hospital emergency departments (EDs) serve an aging population with
      an increased burden on health resources. Few studies have examined the effects of
      comprehensive geriatric assessment interventions on ED use. This study aimed to
      systematically review the literature and compare the effects of these
      interventions on ED visits. METHODS: Relevant articles were identified through
      electronic databases and a search of reference lists and personal files.
      Inclusion criteria included: original research (written in English or French) on
      interventions conducted in noninstitutionalized populations 60 years old or
      older, not restricted to a particular medical condition, in which ED visits were
      a study outcome. Data were abstracted and checked by the first author and a
      research assistant using a standard protocol. RESULTS: Twenty-six relevant
      studies were identified, reported in 28 articles, with study samples obtained
      from EDs (9), hospitals (4), outpatient or primary care settings (10), home care
      (4), and community (1). The study designs included 17 randomized controlled
      trials, 3 trials with nonrandom allocation, 4 before-after studies, 1 quasi
      experimental time-series study, and 1 cross-sectional study. Hospital-based
      interventions (mostly short-term assessment and/or liaison) had little overall
      effect on ED utilization, whereas many interventions in outpatient and/or primary
      care or home care settings (including geriatric assessment and management and
      case management) reduced ED utilization. Heterogeneity in study methods, measures
      of comorbidity, functional status, and ED utilization precluded meta-analysis of
      the results. CONCLUSION: Further research, using improved methodologies and
      standardized measures, is needed to address the effects of innovative geriatric
      interventions on ED visits.

PMID- 16456195
TI  - Aged men experience disturbances in recovery following submaximal exercise.
AB  - BACKGROUND: Physiological responses to exercise of moderate intensity and
      duration among aged compared to young adults have yet to be clearly defined.
      Further, the effects of aging on the rate and effectiveness of postexercise
      recovery are unknown. METHODS: Here, selected physiological responses during and
      following exercise of the same relative intensity were examined in untrained
      young and aged men. RESULTS: Generally, the two groups displayed similar
      responses during 30 minutes of exercise. During recovery, however, numerous age
      related differences were manifested. Relative heart rate (% peak) was higher
      during recovery among the aged group. Postexercise lactate remained increased
      longer among aged men, and blood glucose regulation was impaired during recovery.
      This difference in circulating glucose was associated with insulin responses
      whereby young, but not aged men experienced a postexercise spike. Unlike that in
      young men, rectal temperature among aged men continued to increase through the
      entire recovery period. CONCLUSIONS: These data suggest that aged men encounter
      problems in recovering from submaximal exercise.

PMID- 16456196
TI  - Strength, but not muscle mass, is associated with mortality in the health, aging
      and body composition study cohort.
AB  - BACKGROUND: Although muscle strength and mass are highly correlated, the
      relationship between direct measures of low muscle mass (sarcopenia) and strength
      in association with mortality has not been examined. METHODS: Total mortality
      rates were examined in the Health, Aging and Body Composition (Health ABC) Study
      in 2292 participants (aged 70-79 years, 51.6% women, and 38.8% black). Knee
      extension strength was measured with isokinetic dynamometry, grip strength with
      isometric dynamometry. Thigh muscle area was measured by computed tomography (CT)
      scan, and leg and arm lean soft tissue mass were determined by dual energy x-ray
      absorptiometry (DXA). Both strength and muscle size were assessed as in gender
      specific Cox proportional hazards models, with age, race, comorbidities, smoking
      status, level of physical activity, fat area by CT or fat mass by DXA, height,
      and markers of inflammation, including interleukin-6, C-reactive protein, and
      tumor necrosis factor-alpha considered as potential confounders. RESULTS: There
      were 286 deaths over an average of 4.9 (standard deviation = 0.9) years of follow
      up. Both quadriceps and grip strength were strongly related to mortality. For
      quadriceps strength (per standard deviation of 38 Nm), the crude hazard ratio for
      men was 1.51 (95% confidence interval, 1.28-1.79) and 1.65 (95% confidence
      interval, 1.19-2.30) for women. Muscle size, determined by either CT area or DXA
      regional lean mass, was not strongly related to mortality. In the models of
      quadriceps strength and mortality, adjustment for muscle area or regional lean
      mass only slightly attenuated the associations. Further adjustment for other
      factors also had minimal effect on the association of quadriceps strength with
      mortality. Associations of grip strength with mortality were similar. CONCLUSION:
      Low muscle mass did not explain the strong association of strength with
      mortality, demonstrating that muscle strength as a marker of muscle quality is
      more important than quantity in estimating mortality risk. Grip strength provided
      risk estimates similar to those of quadriceps strength.

PMID- 16456197
TI  - Power training improves balance in healthy older adults.
AB  - BACKGROUND: Age-related decline in muscle power may be an early indicator of
      balance deficits and fall risk, even in nonfrail adults. This study examined the
      dose-dependent effect of power training on balance performance in healthy older
      adults. METHODS: One hundred twelve community-dwelling healthy older adults (69
      +/- 6 years) were randomized to 8-12 weeks of power training at 20% (LOW), 50%
      (MED), or 80% (HIGH) of maximal strength, or a nontraining control (CON) group.
      Participants trained twice weekly (five exercises; three sets of eight rapid
      concentric/slow eccentric repetitions) using pneumatic resistance machines.
      Balance, muscle performance (strength, power, endurance, contraction velocity),
      and body composition were measured. RESULTS: Power training significantly
      improved balance performance (p =.006) in participants who underwent power
      training compared to controls. Low intensity power training produced the greatest
      improvement in balance performance (p =.048). Average contraction velocity at low
      load (40% one repetition maximum [1RM]) at baseline independently predicted
      improvement in balance following training (r = -.29, p =.004). CONCLUSIONS: Power
      training improves balance, particularly using a low load, high velocity regimen,
      in older adults with initial lower muscle power and slower contraction. Further
      studies are warranted to define the mechanisms underlying this adaptation, as
      well as the optimum power training intensity for a range of physiological and
      clinical outcomes in older adults with varying levels of health status and
      functional independence.

PMID- 16456198
TI  - Low socioeconomic status and disability in old age: evidence from the InChianti
      study for the mediating role of physiological impairments.
AB  - BACKGROUND: Low socioeconomic status (SES) has been associated with increased
      risk of disability in later life. The purpose of this study was to determine if
      SES has an impact on mobility functioning and to explore which physiological
      impairments are also associated with SES and may explain its relationship with
      mobility. METHODS: The study sample consisted of 1025 individuals aged 65 years
      or older residing in the Chianti area (Italy). Number of years of education was
      used as an indicator of SES. Mobility functioning was assessed using gait speed
      (400 m) and the Short Physical Performance Battery (SPPB). Mobility-related
      physiological impairments were assessed with tests of executive functioning,
      nerve conduction velocity, muscle power, hip-ankle range of motion, Ankle
      Brachial Index, and visual acuity. Linear regression models were used to study
      the association between number of years of education and mobility and to estimate
      the contribution of each of the selected physiological impairments to this
      association. RESULTS: Adjusting for age and sex, slower gait speed (1.16 vs 1.26
      m/s, p <.0001) and lower SPPB scores (9.55 vs 10.11, p =.006) were seen in
      persons with < or =5 years of total education compared with those persons with >5
      years of total education. Leg power and executive function decreased the strength
      of the association between educational level and gait speed by more than 15%.
      Controlling for all selected impairments (full model) decreased the education
      gait speed association by 49%. Low education continued to be significantly
      associated with gait speed (p <.01). Adjusting for all physiological impairments
      substantially reduced the low education-SPPB score association by 100%, and this
      association was no longer significant. CONCLUSIONS: Low SES is related to
      multiple physiological impairments, which explain a large amount of the
      association between education and gait limitations. Further work must be done to
      understand the mechanisms whereby low SES translates into the impairments that
      play an important role in mobility.

PMID- 16456199
TI  - Endogenous hormones, muscle strength, and risk of fall-related fractures in older
      women.
AB  - BACKGROUND: Among older people, fracture-causing fall often leads to health
      deterioration. The role of endogenous hormone status and muscle strength on fall
      related fracture risk is unclear. This study investigates if, after adjustment
      for bone density, endogenous hormones and muscle strength would predict fall
      related limb fracture incidence in older community-dwelling women followed-up
      over 10 years. METHODS: As a part of a prospective population-based study, 187 75
      year-old women were investigated. Serum estradiol, testosterone, sex hormone
      binding globulin, and dehydroepiandrosterone sulfate concentrations were
      analyzed, and isometric muscle strength and bone mineral density were assessed.
      Fall-related limb fractures were gathered from patient records. RESULTS: Serum
      estradiol concentration was a significant predictor of fall-related limb
      fractures. Women with serum estradiol concentrations less than 0.022 nmol/L had a
      3-fold risk (relative risk 3.05; 95% confidence interval, 1.26-7.36), and women
      with estradiol concentrations between 0.022 and 0.066 nmol/L doubled the risk
      (relative risk 2.24; 95% confidence interval, 0.97-5.19) of fall-related limb
      fracture compared to the women with estradiol concentrations ()above 0.066
      nmol/L. Adjustment for muscle strength and bone mineral density did not
      materially change the risk estimates. High muscle strength was associated with a
      low incidence of fall-related limb fractures. CONCLUSIONS: This study showed that
      in 75-year-old women higher serum estradiol concentration and greater muscle
      strength were independently associated with a low incidence of fall-related limb
      fractures even after adjustment for bone density. Our results suggest that
      hormonal status and muscle strength have their own separate mechanisms protecting
      from fall-related fractures. This finding is of importance in developing
      preventive strategies, but calls for further study.

PMID- 16456200
TI  - Associations of changes in exercise level with subsequent disability among
      seniors: a 16-year longitudinal study.
AB  - BACKGROUND: The effect of changes in physical exercise on progression of
      musculoskeletal disability in seniors has rarely been studied. METHODS: We
      studied a prospective cohort annually from 1984 to 2000 using the Health
      Assessment Questionnaire Disability Index (HAQ-DI). The cohort included 549
      participants, 73% men, with average end-of-study age of 74 years. At baseline and
      at the end of the study, participants were classified as "High" or "Low" vigorous
      exercisers using a cut-point of 60 min/wk. Four groups were formed: "Sedentary"
      (Low-->Low; N = 71), "Exercise Increasers" (Low-->High; N = 27), "Exercise
      Decreasers" (High-->Low; N = 73), and "Exercisers" (High-->High; N = 378). The
      primary dependent variable was change in HAQ-DI score (scored 0-3) from 1984 to
      2000. Multivariate statistical adjustments using analysis of covariance included
      age, gender, and changes in three risk factors, body mass index, smoking status,
      and number of comorbid conditions. Participants also prospectively provided
      reasons for exercise changes. RESULTS: At baseline, Sedentary and Increasers
      averaged little exercise (16 and 22 exercise min/wk), whereas Exercisers and
      Decreasers averaged over 10 times more (285 and 212 exercise min/wk; p <.001).
      All groups had low initial HAQ-DI scores, ranging from 0.03 to 0.08. Increasers
      and Exercisers achieved the smallest increments in HAQ-DI score (0.17 and 0.11)
      over 16 years, whereas Decreasers and Sedentary fared more poorly (increments
      0.27 and 0.37). Changes in HAQ-DI score for Increasers compared to Sedentary were
      significantly more favorable (p <.05) even after multivariate statistical
      adjustment. CONCLUSIONS: Inactive participants who increased exercise achieved
      excellent end-of-study values with increments in disability similar to those
      participants who were more active throughout. These results suggest a beneficial
      effect of exercise, even when begun later in life, on postponement of disability.

PMID- 16456201
TI  - More nursing, fewer deaths.

PMID- 16456202
TI  - Impact of nursing on hospital patient mortality: a focused review and related
      policy implications.
AB  - Understanding the determinants of patient mortality can lead to the development
      of strategies that reduce mortality and prevent unnecessary death. This paper
      synthesizes the body of published research that explores determinants of
      mortality for patients who have experienced acute care hospitalization. Fifteen
      research manuscripts were found to meet the selection criteria through an
      electronic search in MEDLINE and CINAHL (1986-2004). Seven categories of
      determinants of mortality were found: nurse-physician relationships, nurse
      staffing characteristics, physician characteristics, professional practice
      environment, nurse experience, registered nurse educational preparation, and
      clinical nursing support. Implications and recommendations for improving quality
      and safety in hospital care are discussed.

PMID- 16456203
TI  - Improving the management and referral of patients with transient ischaemic
      attacks: a change strategy for a health community.
AB  - PROBLEM: Rapid referral and management of patients with transient ischaemic
      attacks is a key component in the national strategy for stroke prevention.
      However, patients with transient ischaemic attacks are poorly identified and
      undertreated. DESIGN AND SETTING: Before and after evaluation of quality
      improvement programme with controlled comparison in three primary care trusts
      reflecting diverse populations and organisational structures in an urban district
      in the North of England. KEY MEASURES FOR IMPROVEMENT: The proportion of patients
      receiving antiplatelet drugs and safe driving advice on referral to a specialty
      clinic, and the numbers of referrals, adjusted for age, to the specialist clinic
      before and after the improvement programme. STRATEGIES FOR CHANGE: Interviews
      with patient and professionals to identify gaps and barriers to good practice;
      development of evidence based guidelines for the management of patients with
      transient ischaemic attacks; interactive multidisciplinary workshops for each
      primary care trust with feedback of individual audit results of referral
      practice; outreach visits to teams who were unable to attend the workshops;
      referral templates and desktop summaries to provide reminders of the guidelines
      to clinicians; incorporation of standards into professional contracts. EFFECTS OF
      CHANGE: A significant improvement occurred in identification and referral of
      patients with transient ischaemic attacks to specialist clinics, with a 41%
      increase in referrals from trained practices compared with control practices.
      There were also significant improvements in the early treatment and safety advice
      provided to patients before referral. LESSONS LEARNT: A strategic approach to
      effective quality improvement across a diverse health community is feasible and
      achievable. Careful planning with patient and professional involvement to develop
      a tailored and multifaceted quality improvement programme to implement evidence
      based practice can work in very different primary care settings. Key components
      of the effectiveness of the model include contextual analysis, strong
      professional support, clear recommendations based on robust evidence, simplicity
      of adoption, good communication, and use of established networks and opinion
      leaders.

PMID- 16456204
TI  - Relationship between patient complaints and surgical complications.
AB  - BACKGROUND: Patient complaints are associated with increased malpractice risk but
      it is unclear if complaints might be associated with medical complications. The
      purpose of this study was to determine whether an association exists between
      patient complaints and surgical complications. METHODS: A retrospective analysis
      of 16,713 surgical admissions was conducted over a 54 month period at a single
      academic medical center. Surgical complications were identified using
      administrative data. The primary outcome measure was unsolicited patient
      complaints. RESULTS: During the study period 0.9% of surgical admissions were
      associated with a patient complaint. 19% of admissions associated with a patient
      complaint included a postoperative complication compared with 12.5% of admissions
      without a patient complaint (p = 0.01). After adjusting for surgical specialty,
      co-morbid illnesses and length of stay, admissions with complications had an odds
      ratio of 1.74 (95% confidence interval 1.01 to 2.98) of being associated with a
      complaint compared with admissions without complications. CONCLUSIONS: Admissions
      with surgical complications are more likely to be associated with a complaint
      than surgical admissions without complications. Further research is necessary to
      determine if patient complaints might serve as markers for poor clinical
      outcomes.

PMID- 16456205
TI  - Relationship between complaints and quality of care in New Zealand: a descriptive
      analysis of complainants and non-complainants following adverse events.
AB  - OBJECTIVES: To estimate the proportion and characteristics of patients injured by
      medical care in New Zealand public hospitals who complain to an independent
      health ombudsman, the Health and Disability Commissioner ("the Commissioner").
      DESIGN: The percentage of injured patients who lodge complaints was estimated by
      linking the Commissioner's complaints database to records reviewed in the New
      Zealand Quality of Healthcare Study (NZQHS). Bivariate and multivariate analyses
      investigated sociodemographic and socioeconomic differences between complainants
      and non-complainants. SETTING: New Zealand public hospitals and the Office of the
      Commissioner in 1998. POPULATION: Patients who lodged claims with the
      Commissioner (n = 398) and patients identified by the NZQHS as having suffered an
      adverse event who did not lodge a complaint with the Commissioner (n = 847). MAIN
      OUTCOME MEASURES: Adverse events, preventable adverse events, and complaints
      lodged with the Commissioner. RESULTS: Among adverse events identified by the
      NZQHS, 0.4% (3/850) resulted in complaints; among serious, preventable adverse
      events 4% (2/48) resulted in complaints. The propensity of injured patients to
      complain increased steeply with the severity of the injury: odds of complaint
      were 11 times greater after serious permanent injuries than after temporary
      injuries, and 18 times greater after deaths. Odds of complaining were
      significantly lower for patients who were elderly (odds ratio (OR) 0.2, 95%
      confidence interval (CI) 0.1 to 0.4), of Pacific ethnicity (OR 0.3, 95% CI 0.1 to
      0.9), or lived in the most deprived areas (OR 0.3, 95% CI 0.2 to 0.6).
      CONCLUSION: Most medical injuries never trigger a complaint to the Commissioner.
      Among complaints that are brought, severe and preventable injuries are common,
      offering a potentially valuable "window" on serious threats to patient safety.
      The relatively low propensity to complain among patients who are elderly,
      socioeconomically deprived, or of Pacific ethnicity suggests troubling
      disparities in access to and utilisation of complaints processes.

PMID- 16456206
TI  - Interventions in primary care to reduce medication related adverse events and
      hospital admissions: systematic review and meta-analysis.
AB  - OBJECTIVE: To identify and evaluate studies of interventions in primary care
      aimed at reducing medication related adverse events that result in morbidity,
      hospital admission, and/or mortality. METHODS: Fourteen electronic databases were
      systematically searched for published and unpublished data. Bibliographies of
      retrieved papers were searched and experts and first authors contacted in an
      attempt to locate additional studies. There were no restrictions on language of
      publication. All interventions applied in primary care settings which aimed to
      improve patient safety by reducing adverse events resulting from medication
      overuse or misuse were considered. Randomised controlled trials, controlled
      trials, controlled before and after studies, and interrupted time series studies
      were eligible for inclusion. Study quality assessment and data extraction were
      undertaken using the Cochrane Effective Practice and Organisation of Care data
      collection checklist and template. Meta-analysis was performed using a random
      effects model. RESULTS: 159 studies were initially identified, of which 38
      satisfied our inclusion criteria. These were categorised as follows: 17
      pharmacist-led interventions (of which 15 reported hospital admissions as an
      outcome); eight interventions led by other primary healthcare professionals that
      reported preventable drug related morbidity as an outcome; and 13 complex
      interventions that included a component of medication review aimed at reducing
      falls in the elderly (the outcome being falls). Meta-analysis found that
      pharmacist-led interventions are effective at reducing hospital admissions (OR
      0.64 (95% CI 0.43 to 0.96)), but restricting analysis to the randomised
      controlled trials failed to demonstrate significant benefit (OR 0.92 (95% CI 0.81
      to 1.05)). Pooling the results of studies in the other categories did not
      demonstrate any significant effect. CONCLUSIONS: There is relatively weak
      evidence to indicate that pharmacist-led medication reviews are effective in
      reducing hospital admissions. There is currently no evidence for the
      effectiveness of other interventions which aim at reducing admissions or
      preventable drug related morbidity. More randomised controlled trials of primary
      care based pharmacist-led interventions are needed to decide whether or not this
      intervention is effective in reducing hospital admissions.

PMID- 16456207
TI  - Exploring obstacles to proper timing of prophylactic antibiotics for surgical
      site infections.
AB  - BACKGROUND: Surgical site infections remain one of the leading types of
      nosocomial infections. The administration of prophylactic antibiotics within a
      specific interval has been shown to reduce the burden of surgical site
      infections, but adherence to proper timing guidelines remains problematic. This
      study examined perceived obstacles to the use of evidence-based guidelines for
      the timely administration of prophylactic antibiotics to prevent surgical site
      infections. METHODS: 27 semi-structured interviews were conducted with
      anesthesiologists (n = 12), surgeons (n = 11), and perioperative administrators
      (n = 4) in two large academic hospitals to elicit their perceptions of the
      factors that prevent the timely administration of prophylactic antibiotics. Using
      a grounded theory approach, transcripts were analyzed for recurrent themes.
      RESULTS: Despite having knowledge of guidelines, participants perceived
      consistent failure in the proper timing of antibiotic administration. Thematic
      analysis revealed a number of obstacles to the observance of guidelines
      including: (1) low priority, (2) inconvenience, (3) workflow, (4) organizational
      communication, and (5) role perception. Workflow and role perception were the
      dominant obstacles. CONCLUSION: This study suggests that proper antibiotic timing
      is thwarted by significant obstacles. The gap between evidence-based guidelines
      and practice is populated by individual values, professional conflicts, and
      organizational conflicts which must be addressed in order to achieve optimal
      practice in this domain. Using group interviews to reveal these factors to team
      members and managers may be a first step to resolving the gap and reducing
      surgical site infections.

PMID- 16456208
TI  - Attitudes and barriers to incident reporting: a collaborative hospital study.
AB  - OBJECTIVES: To assess awareness and use of the current incident reporting system
      and to identify factors inhibiting reporting of incidents in hospitals. DESIGN,
      SETTING AND PARTICIPANTS: Anonymous survey of 186 doctors and 587 nurses from
      diverse clinical settings in six South Australian hospitals (response rate =
      70.7% and 73.6%, respectively). MAIN OUTCOME MEASURES: Knowledge and use of the
      current reporting system; barriers to incident reporting. RESULTS: Most doctors
      and nurses (98.3%) were aware that their hospital had an incident reporting
      system. Nurses were more likely than doctors to know how to access a report
      (88.3% v 43.0%; relative risk (RR) 2.05, 95% CI 1.61 to 2.63), to have ever
      completed a report (89.2% v 64.4%; RR 1.38, 95% CI 1.19 to 1.61), and to know
      what to do with the completed report (81.9% v 49.7%; RR 1.65, 95% CI 1.27 to
      2.13). Staff were more likely to report incidents which are habitually reported,
      often witnessed, and usually associated with immediate outcomes such as patient
      falls and medication errors requiring corrective treatment. Near misses and
      incidents which occur over time such as pressure ulcers and DVT due to inadequate
      prophylaxis were least likely to be reported. The most frequently stated barrier
      to reporting for doctors and nurses was lack of feedback (57.7% and 61.8%
      agreeing, respectively). CONCLUSIONS: Both doctors and nurses believe they should
      report most incidents, but nurses do so more frequently than doctors. To improve
      incident reporting, especially among doctors, clarification is needed of which
      incidents should be reported, the process needs to be simplified, and feedback
      given to reporters.

PMID- 16456209
TI  - Quality improvement of oral medication administration in patients with enteral
      feeding tubes.
AB  - BACKGROUND: The correct administration of oral drugs to patients on enteral tube
      feeding presents a special challenge. As patients are usually unable to swallow
      oral drugs and many drugs should not be crushed, ways have to be found to
      administer them through the feeding tube. Measures to improve the quality of oral
      drug administration in patients with enteral feeding tubes may consist of
      introducing guidelines, training nurses, or giving patient-tailored advice by the
      pharmacy. An integrated program comprising all these measures is likely to result
      in the greatest improvements. METHODS: A study was undertaken in two Dutch
      hospitals to investigate the effect of such an integrated program. RESULTS: The
      integrated program in hospital I resulted in a decrease in the number of tube
      obstructions (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.047 to 1.05).
      There was a significant decrease in the number of administration errors per nurse
      in hospital II (OR 0.003, 95% CI 0.0005 to 0.02). CONCLUSIONS: This
      multidisciplinary program comprising several interventions to promote the correct
      administration of drugs through an enteral feeding tube results in substantial
      improvements. As errors concerning administration of drugs to patients with
      enteral feeding tubes may lead to adverse drug events and loss of effect, these
      improvements are likely to contribute to a decrease in patient morbidity.

PMID- 16456210
TI  - Likelihood of reporting adverse events in community pharmacy: an experimental
      study.
AB  - BACKGROUND: In the UK the National Reporting and Learning System (NRLS) is
      designed to coordinate the reporting of patient safety incidents nationally and
      to improve the ability of the health service to learn from the analysis of these
      events. Little is known about levels of engagement with the NRLS. OBJECTIVE: To
      examine the likelihood of community pharmacists and support staff reporting
      patient safety incidents which occur in community pharmacies. METHODS:
      Questionnaire survey containing nine incident scenarios. In the scenarios two
      factors were orthogonally manipulated: the outcome for the patient was reported
      as good, bad or poor, and the behaviour of the pharmacist was described as either
      complying with a protocol, not being aware of a protocol (error), or violating a
      protocol. Respondents were asked to rate whether they would report the incident
      (1) locally within the pharmacy and (2) nationally to the National Patient Safety
      Agency (NPSA). RESULTS: 275 questionnaires were returned (79% response rate) from
      223 community pharmacists and 52 members of support staff. There were significant
      main effects for both patient outcome (F(2,520) = 18.19, p<0.001) and behaviour
      type (F(2,520) = 93.98, p<0.001), indicating that pharmacists and support staff
      would take into account both the outcome of the behaviour and whether or not it
      follows a protocol when considering to report an incident within the pharmacy.
      Likewise, both pharmacists and support staff considered patient outcome (F(2,524)
      = 12.59, p<0.001) and behaviour type (F(2,524) = 34.82, p<0.001) when considering
      to report to the NPSA. Both locally and nationally, the likelihood of reporting
      any incident was low, and judgements on whether to report were more affected by
      the behaviour of the pharmacist in relation to protocols than the resulting
      outcome for the patient. CONCLUSIONS: Community pharmacists and their support
      staff would be unlikely to report adverse incidents if they witnessed them
      occurring in a community pharmacy. They remain to be convinced that the
      advantages to them and their patients outweigh the consequences of blame.

PMID- 16456211
TI  - Factors predicting the guideline compliant supply (or non-supply) of non
      prescription medicines in the community pharmacy setting.
AB  - BACKGROUND: The reclassification of prescription only medicines to pharmacy and
      general sales list medicines (also known as non-prescription medicines) provides
      the public with greater access to medicines that they can purchase for self-care.
      There is evidence that non-prescription medicines may be associated with
      inappropriate supply. This study investigated factors predicting evidence-based
      (guideline compliant) supply or non-supply of non-prescription medicines. METHOD:
      Secondary analysis of results from a randomised controlled trial of educational
      interventions to promote the evidence based supply of non-prescription medicines.
      Ten actors made simulated patient (customer) visits to 60 community pharmacies
      using seven scenarios reflecting different types of presentations. The dependent
      variable was appropriate (guideline compliant) supply of antifungal medication
      for treatment of vaginal candidiasis. RESULTS: No significant association was
      shown between guideline compliant behaviour and pharmacy type or location, or
      with the actor making the visit. The likelihood of guideline compliant outcome
      was significantly greater with symptom presentations than with condition or
      product presentations (p < 0.001). The likelihood of a guideline compliant
      outcome increased (a) as more information was exchanged (p < 0.001), (b) with the
      use of WWHAM (a mnemonic frequently used by medicine counter assistants during
      consultations for non-prescription medicines) (p < 0.001); (c) when specific
      WWHAM questions were used (including "description of symptoms" (p < 0.001) and
      "whether other medication was currently being used" (p < 0.001); and (d) in
      consultations involving solely pharmacists compared with those involving only
      medicine counter assistants (p = 0.017). After adjustment for presentation type,
      a significant association persisted between appropriate outcome and consultations
      with WWHAM scores of 2 and > or = 3, respectively. CONCLUSIONS: The nature and
      extent of information exchange between pharmacy staff and customers has a strong
      influence on the guideline compliant supply of non-prescription medicines. Future
      interventions to promote the safe and effective use of non-prescription medicines
      should address the apparent deficit in communication between pharmacy staff in
      general, and medicine counter assistants in particular, which may reflect both
      pharmacy staff skills and customer expectations.

PMID- 16456212
TI  - Health Care Failure Mode and Effect Analysis: a useful proactive risk analysis in
      a pediatric oncology ward.
AB  - BACKGROUND: Pediatric inpatient settings are known for their high medication
      error rate. The aim of this study was to investigate whether the Health Care
      Failure Mode and Effect Analysis (HFMEA) is a valid proactive method to evaluate
      circumscribed health care processes like prescription up to and including
      administration of chemotherapy (vincristine) in the pediatric oncology inpatient
      setting. METHODS: A multidisciplinary team consisting of a team leader, pharmacy,
      nursing and medical staff and a patient's parent was assembled in a pediatric
      oncology ward with a computerized physician order entry system. A flow diagram of
      the process was made and potential failure modes were identified and evaluated
      using a hazard scoring matrix. Using a decision tree, it was determined for which
      failure mode recommendations had to be made. RESULTS: The process was divided
      into three main parts: prescription, processing by the pharmacy, and
      administration. Fourteen out of 61 failure modes were classified as high risk, 10
      of which were sufficiently covered by current protocols. For the other four
      failure modes, five recommendations were made. Four additional recommendations
      were made concerning non-high risk failure modes. Most of them were implemented
      by the hospital management. The whole process took seven meetings and a total of
      140 man-hours. CONCLUSIONS: The systematic approach of HFMEA by a
      multidisciplinary team is a useful method for detecting failure modes. A patient
      or a parent of a patient contributes to the multidisciplinarity of the team.

PMID- 16456213
TI  - Prediction of pressure ulcer development in hospitalized patients: a tool for
      risk assessment.
AB  - OBJECTIVES: To identify independent predictors for development of pressure ulcers
      in hospitalized patients and to develop a simple prediction rule for pressure
      ulcer development. DESIGN: The Prevention and Pressure Ulcer Risk Score
      Evaluation (prePURSE) study is a prospective cohort study in which patients are
      followed up once a week until pressure ulcer occurrence, discharge from hospital,
      or length of stay over 12 weeks. Data were collected between January 1999 and
      June 2000. SETTING: Two large hospitals in the Netherlands. PARTICIPANTS: Adult
      patients admitted to the surgical, internal, neurological and geriatric wards for
      more than 5 days were eligible. A consecutive sample of 1536 patients was
      visited, 1431 (93%) of whom agreed to participate. Complete follow up data were
      available for 1229 (80%) patients. MAIN OUTCOME MEASURES: Occurrence of a
      pressure ulcer grade 2 or worse during admission to hospital. RESULTS:
      Independent predictors of pressure ulcers were age, weight at admission, abnormal
      appearance of the skin, friction and shear, and planned surgery in coming week.
      The area under the curve of the final prediction rule was 0.70 after
      bootstrapping. At a cut off score of 20, 42% of the patient weeks were identified
      as at risk for pressure ulcer development, thus correctly identifying 70% of the
      patient weeks in which a pressure ulcer occurred. CONCLUSION: A simple clinical
      prediction rule based on five patient characteristics may help to identify
      patients at increased risk for pressure ulcer development and in need of
      preventive measures.

PMID- 16456215
TI  - Drug innovation and patient safety--the need for a new paradigm.

PMID- 16456214
TI  - Advertising, ethics and the competitive practice of medicine: Charles Elton
      Blanchard MD.

PMID- 16456216
TI  - A randomized, controlled effectiveness trial of OROS-methylphenidate compared to
      usual care with immediate-release methylphenidate in attention deficit
      hyperactivity disorder.
AB  - BACKGROUND: The thrice daily dosing regimen of immediate release methylphenidate
      (IR-MPH) for Attention Deficit/Hyperactivity Disorder (ADHD) requires in-school
      dosing, leading to issues surrounding dispensing and storage of controlled
      substances by school personnel and concerns over children?s privacy and the
      embarrassment associated with taking medication in public at school. OROS
      methylphenidate (OROS-MPH) is a once-daily controlled-release formulation of
      methylphenidate (MPH) developed to overcome some of the limitations associated
      with IR-MPH and first-generation sustained-release formulations. Randomized,
      controlled trials (RCTs) that focus on treatment efficacy provide the best
      evidence for demonstrating whether an intervention works, but under ideal
      conditions one cannot discount the importance of efficacy study results. However,
      the most useful information to clinicians comes from an effectiveness study
      design. OBJECTIVES: To evaluate the effectiveness and tolerability of OROS-MPH
      versus usual care with IR-MPH in children aged 6 to 12 years with ADHD. METHODS:
      This 8 week, multicentre, open-label study randomized 147 subjects to either once
      daily OROS-MPH or usual care with IR-MPH. Subjects were titrated to a clinically
      effective dose of either study medication over 4 weeks and maintained on that
      dose for an additional 4 weeks. The SNAP-IV parent-rating scale was used to
      assess effectiveness. RESULTS: OROS-MPH showed statistically significant
      superiority to IR-MPH in remission rate based on the 18 ADHD symptoms (p=0.0002,
      X2=13.8, df=1) and severity of ADHD and ODD symptoms (p=0.004, F=8.4, df=1,127),
      as well as on the following secondary assessments: IOWA Conners, Conners Parent
      Rating Scale (short version), Parent Stress Index, (short version); Visual
      Analogue Scale for social play; Clinical Global Impression-Severity, Clinical
      Global Impression-Improvement and Parent Satisfaction with treatment. OROS-MPH
      and IR-MPH were both well tolerated with a similar side effect profile.
      CONCLUSIONS: Once-daily OROS-MPH is significantly more effective than usual care
      with IR-MPH based on multiple outcome measures including remission rate.

PMID- 16456217
TI  - A comparison of methylphenidate formulations in the treatment of ADHD.

PMID- 16456218
TI  - The Canadian Hypertension Education Program (CHEP)--a therapeutic knowledge
      translation program.
AB  - The Canadian Hypertension Education Program (CHEP) is a dynamic therapeutic
      knowledge translation program that changes annually based on the previous year's
      experience. To meet the challenge of hypertension treatment and control, CHEP
      activities include updating evidence-based management recommendations,
      implementing the recommendations and examining the impact of CHEP on hypertension
      management and hypertensive complications. CHEP aids health care professionals by
      providing credible, widely dissentinated up-to-date recommendations in multiple
      formats to suit individual learning needs. Key words: Hypertension, knowledge
      translation.

PMID- 16456219
TI  - Persistent tardive rebound panic disorder, rebound anxiety and insomnia following
      paroxetine withdrawal: a review of rebound-withdrawal phenomena.
AB  - OBJECTIVE: To describe tardive rebound anxiety phenomena (panic, anxiety and
      insomnia) following abrupt paroxetine discontinuation. METHOD: Case report, with
      comprehensive literature review on rebound and withdrawal phenomena associated
      with psychotropic medications. RESULTS: Three different discontinuation syndromes
      with psychotropics are described: (1) new-onset CNS-depressant type withdrawal
      symptoms (minor and major); (2) rebound syndromes; and (3) supersensitivity
      symptoms. Abrupt paroxetine discontinuation has been well described and fits the
      first category. Tardive rebound panic disorder-phenomena with paroxetine has some
      features of the supersensitivity category. CONCLUSION: Chronic paroxetine
      treatment may lead to 5-HT2-receptor down regulation, with desensitization of 5
      HT1A and 5-HT2 receptors, which may contribute to tardive rebound symptoms upon
      abrupt withdrawal. Early reports suggest that genetic factors may also contribute
      to withdrawal symptoms in susceptible individuals. Cholinergic rebound may also
      occur and could explain tardive insomnia and anxiety in paroxetine withdrawal.

PMID- 16456220
TI  - Preserved coupling of oxidative phosphorylation but decreased mitochondrial
      respiratory capacity in IL-1beta-treated human peritoneal mesothelial cells.
AB  - The peritoneal mesothelium acts as a regulator of serosal responses to injury,
      infection, and neoplastic diseases. After inflammation of the serosal surfaces,
      proinflammatory cytokines induce an "activated" mesothelial cell phenotype, the
      mitochondrial aspect of which has not previously been studied. After incubation
      of cultured human peritoneal mesothelial cells with interleukin (IL)-1beta for 48
      h, respiratory activity of suspended cells was analyzed by high-resolution
      respirometry. Citrate synthase (CS) and lactate dehydrogenase (LDH) activities
      were determined by spectrophotometry. Treatment with IL-1beta resulted in a
      significant decline of respiratory capacity (p < 0.05). Respiratory control
      ratios (i.e., uncoupled respiration at optimum carbonyl cyanide p
      trifluoromethoxyphenylhydrazone concentration divided by oligomycin inhibited
      respiration measured in unpermeabilized cells) remained as high as 11, indicating
      well-coupled mitochondria and functional integrity of the inner mitochondrial
      membrane. Whereas respiratory capacities of the cells declined in proportion with
      decreased CS activity (p < 0.05), LDH activity increased (p < 0.05). Taken
      together, these results indicate that IL-1beta exposure of peritoneal mesothelial
      cells does not lead to irreversible defects or inhibition of specific components
      of the respiratory chain, but is associated with a decrease of mitochondrial
      content of the cells that is correlated with an increase in LDH (and thus
      glycolytic) capacity.

PMID- 16456221
TI  - Differential regulation of intracellular calcium oscillations by mitochondria and
      gap junctions.
AB  - Fluctuations of intracellular Ca2+ ([Ca2+]i) regulate a variety of cellular
      functions. The classical Ca2+ transport pathways in the endoplasmic reticulum
      (ER) and plasma membrane are essential to [Ca2+]i oscillations. Although
      mitochondria have recently been shown to absorb and release Ca2+ during G protein
      coupled receptor (GPCR) activation, the role of mitochondria in [Ca2+]i
      oscillations remains to be elucidated. Using fluo-3-loaded human teratocarcinoma
      NT2 cells, we investigated the regulation of [Ca2+]i oscillations by
      mitochondria. Both the muscarinic GPCR agonist carbachol and the ER Ca2+
      adenosine triphosphate inhibitor thapsigargin (Tg) induced [Ca2+]i oscillations
      in NT2 cells. The [Ca2+]i oscillations induced by carbachol were unsynchronized
      among individual NT2 cells; in contrast, Tg-induced oscillations were
      synchronized. Inhibition of mitochondrial functions with either mitochondrial
      blockers or depletion of mitochondrial DNA eliminated carbachol--but not Tg
      induced [Ca2+]i oscillations. Furthermore, carbachol-induced [Ca2+]i oscillations
      were partially restored to mitochondrial DNA-depleted NT2 cells by introduction
      of exogenous mitochondria. Treatment of NT2 cells with gap junction blockers
      prevented Tg-induced but not carbachol-induced [Ca2+]i oscillations. These data
      suggest that the distinct patterns of [Ca2+]i oscillations induced by GPCR and Tg
      are differentially modulated by mitochondria and gap junctions.

PMID- 16456222
TI  - The interfacial tension of the lipid membrane formed from lipid-cholesterol and
      lipid-lipid systems.
AB  - Interfacial tension has been determined for phosphatidylcholine-cholesterol,
      phosphatidylcholine-phosphatidylethanolamine, and phosphatidylethanolamine
      cholesterol membranes. Phosphatidylcholine (PC), phosphatidylethanolamine (PE),
      and cholesterol (Ch) were to be investigated, because of their presence in
      biological membranes. Interfacial tension values of pure components are 0.81 x
      10(-3) N/m, 1.67 x 10(-3) N/m, and 2.36 x 10(-3) N/m, respectively. The 1:1
      complexes were formed during formation of the PC-Ch, PC-PE, and PE-Ch lipid
      membranes. The following parameters describing the complexes were determined: A3(
      1), the surface concentrations of the lipid membranes formed from these
      complexes; gamma3, the interfacial tensions of such membranes and K, the
      stability constants of these complexes.

PMID- 16456223
TI  - Jak2 tyrosine kinase: a mediator of both housekeeping and ligand-dependent gene
      expression?
AB  - Jak2 is a nonreceptor tyrosine kinase that is essential for proper animal
      development and physiology. It is activated by ligand-occupied cell-surface
      receptors. Once activated, it then tyrosine phosphorylates the latent cytoplasmic
      transcription factors, termed the signal transducers and activators of
      transcription (STAT) proteins. Thus Jak2 is viewed as a classic mediator of
      ligand-dependent signal transduction. Recent studies, however, suggest that Jak2
      may mediate cellular gene expression outside of the classically defined, ligand
      activated, Jak/STAT-signaling paradigm. Here we review these studies, provide
      additional data, and discuss whether Jak2 is a mediator of ligand-independent
      gene transcription, and, in turn, whether our current understanding of the
      Jak/STAT signaling paradigm should be modified to incorporate these observations.

PMID- 16456224
TI  - Influence of polyelectrolyte multilayer films on the ICAM-1 expression of
      endothelial cells.
AB  - Recently, the use of polyelectrolyte films has been suggested as a new versatile
      technique of surface modification aimed at tissue engineering. In the present
      study, we evaluated the expression of intercellular adhesion molecule (ICAM)-1 of
      endothelial cells (ECs) seeded on two types of polyelectrolyte multilayer films
      either terminated by poly(D-lysine) (PDL) or poly(allylamine hydrochloride)
      (PAH). This work showed that chemical stimulations with tumor necrosis factor
      (TNF)-alpha induced the ICAM-1 expression of ECs differently depending largely on
      the film architecture employed. Compared with PAH-ending films, the PDL-ending
      ones upregulated the ICAM-1 expression of the ECs after a prolonged exposition to
      TNF-alpha, rendering this film type less favorable in tissue engineering.
      Cytochalasin D (an F-actin disrupting agent) showed the involvement of the
      cytoskeleton in the upregulation of ICAM-1 for cells deposited on films
      terminated by PDL. The PAH-ending films did not perturb the ICAM-1 expression of
      ECs and might thus enhance the seeding of ECs in vascular engineering.

PMID- 16456225
TI  - The "unexpected role" of vitamin E in free radical-induced hemolysis of human
      erythrocytes: alpha-tocopherol-mediated peroxidation.
AB  - Vitamin E involves a group of tocopherols and tocotrienols, in which alpha
      tocopherol with the highest biological activity plays a more efficient role in
      advanced lesions with aged oxidized tissues. However, the results of the present
      study reveal that a large amount of endogenous alpha-tocopherol in human low
      density lipoprotein (LDL) in the absence of any other antioxidants may initiate
      additional free radical propagation under low concentration of free radical
      initiator (i.e., 2,2'-azobis(2-amidinopropane hydrochloride) [AAPH], a water
      soluble free radical source) to peroxide polyunsaturated fatty acids in LDL in
      the manner of alpha-tocopherol-mediated peroxidation (TMP). Whether the addition
      of high concentration of exogenous alpha-tocopherol to human erythrocytes under
      low concentration of AAPH can also drive TMP is the concern in this research
      work. Moreover, the hemolysis extent of human erythrocytes peroxidized by AAPH is
      followed easily by the determination of the hemoglobin outside the erythrocytes.
      A series of observations on various concentrations of AAPH-induced hemolysis in
      the presence of various concentrations of exogenous alpha-tocopherol demonstrates
      that the high concentration of exogenous alpha-tocopherol, coupled with low
      concentration of AAPH, can initiate TMP in the free-radical-induced peroxidation
      of human erythrocytes system as well. This result provides direct evidence to
      support TMP theory and expands its application into in vitro erythrocyte system.

PMID- 16456226
TI  - Amyloid fibril formation by a domain of rat cell adhesion molecule.
AB  - Amyloid fibrils are protein aggregates implicated in several amyloidotic
      diseases. Cellular membranes with local decrease in pH and dielectric constant
      are associated with the amyloid formation. In this study, domain 1 of cell
      adhesion molecule CD2 (CD2-1) is used for studying amyloid fibril formation in a
      water/trifluoroethanol (TFE) mixture. CD2-1 is an all beta-sheet protein similar
      in topology to the amyloidogenic light chain variable domain, which deposits as
      amyloid in light chain amyloidosis at acidic pH. When incubated at pH 2.0 in the
      presence of 18% TFE, CD2-1 initiates the process to assemble into amyloid
      fibrils. It has been shown that TFE induces CD2-1 conformational change with a
      chemical transition (C(m)) of 18% (v/v). ANS (1-anilinonapthalene-8-sulfonic
      acid) binding was used to show that the hydrophobic surface becomes exposed under
      these solvent conditions. Our studies indicate that partial formation of a non
      native conformation and the exposure of the hydrophobic interior could be the
      origins of oligomerization and fibril formation of CD2-1.

PMID- 16456227
TI  - A new hypothesis for Ca2+ flows in skeletal muscle and its implications for other
      cell types.
AB  - We offer a new hypothesis to explain calcium flows in skeletal muscle cells. Our
      model accounts for the uptake of Ca2+ from the extracellular fluid, and the
      release of Ca2+ from the sarcoplasmic reticulum (SR/ER) (the endoplasmic
      reticulum in muscle is named sarcoplasmic reticulum); this has engendered
      difficulty in reviews encompassing both muscle and nonmuscle cells. Here we will
      typically refer to the organelle as ER, except when specifically discussing
      muscle cells. The broad consideration of two major, still unexplained properties
      of skeletal muscle function, namely excitation contraction coupling and
      capacitative calcium entry are accounted for in a unitary hypothesis. This model
      allows a reinterpretation of existing data, and points to areas where new
      investigation may be fruitful. While primarily aimed at explaining Ca2+ flows in
      skeletal muscle, we consider findings of other systems to explore the
      implications of this hypothesis for other cell types.

PMID- 16456228
TI  - Imaging cell interactions with native and crosslinked polyelectrolyte
      multilayers.
AB  - The adhesion of primary chondrocytes to polyelectrolyte multilayer films, made of
      poly(l-lysine) (PLL) and hyaluronan (HA), was investigated for native and
      crosslinked films, either ending by PLL or HA. Crosslinking the film was achieved
      by means of a water-soluble carbodiimide in combination with N
      hydroxysulfosuccinimide. The adhesion of macrophages and primary chondrocytes was
      investigated by microscopical techniques (optical, confocal, and atomic),
      providing useful information on the cell/film interface. Native films were found
      to be nonadhesive for the primary chondrocytes, but could be degraded by
      macrophages, as could be visualized by confocal laser scanning microscopy after
      film labeling. Confocal microscopy images show that these films can be deformed
      by the chondrocytes and that PLL diffuses at the chondrocyte membrane. In
      contrast, the cells adhered and proliferated well on the crosslinked films, which
      were not degraded by the macrophages. These results were confirmed by a MTT test
      over a 6-d period and by atomic force microscopy observations. We thus prove that
      chemical crosslinking can dramatically change cell adhesion properties, the cells
      being more stably anchored on the crosslinked films.

PMID- 16456229
TI  - Theoretical description of the ion transport across nanopores with titratable
      fixed charges: analogies between ion channels and synthetic pores.
AB  - Recently developed nanometer-sized synthetic pores display several properties so
      far believed to be distinctive features of a large variety of biological wide ion
      channels. Thus conductance in the pS-nS range, pH-dependent ion selectivity,
      fluctuations of current between open and closed states, flux inhibition caused by
      protons or divalent cations, current rectification, and the ability to perform
      selective macromolecule sizing and counting are found in synthetic and biological
      channels alike. Despite other differences such as pore size and geometry, the
      similarities open a new field for exploring specific technological applications
      via the chemical modification of synthetic pores with biological molecules. This
      article reviews some of the basic concepts and theories relevant to ion transport
      in nanopores with titratable charges stressing the analogies between synthetic
      pores and biological ion channels. The ultimate goal is to show that continuum
      theories may account for the essential features of these systems. A simple
      electrodiffusion model and its comparison with experimental results are chosen as
      a case study.

PMID- 16456230
TI  - DNA microarray analysis for human congenital heart disease.
AB  - Right ventricular hypertrophy and failure are prominent features in cyanotic
      congenital heart disease, tetralogy of Fallot (TF). Patients with TF require
      primary cardiac surgery at a very young age. To gain insight into the underlying
      molecular mechanisms of right ventricular hypertrophy and to identify gene(s)
      involved in TF, differential gene expression profile was assessed using
      expression-based microarray technology on right ventricular biopsies from young
      TF patients who underwent primary correction. By using quantitative immuno
      histochemistry, expression of vascular endothelial growth factor (VEGF), flk-1,
      and extracellular matrix (ECM) proteins (collagens and fibronectin) as well as
      vessel counts and myocyte cell size was evaluated in TF patients in relation to
      age-matched controls. Among 236 genes showing altered expression pattern in TF
      patients, VEGF (1.8-fold) and ECM markers were clearly upregulated (fibronectin,
      2.4-fold; collagen Ialpha, 7.5-fold; and collagen III, 4.4-fold); flk-1 and most
      matrix metalloproteinases (MMPs) remained unchanged, except the levels of MMP-13
      and -17 declined. Tissue inhibitors of metalloproteinases showed a downregulated
      pattern. Staining of VEGF in cardiomyocytes and of ECM proteins (fibronectin,
      collagen I and III) in interstitial as well as in perivascular area was increased
      (p < 0.01) in TF patients. Morphometric analysis revealed enhanced vascular
      density (p < 0.05) with unchanged wall thickness and enlarged myocyte cross
      sectional areas (p < 0.01) with linear correlation (p < 0.01) with the age in TF
      1 patients. We conclude that the upregulation of genes encoding VEGF and ECM
      proteins are the key events contributing to right ventricular hypertrophy and
      stunted angiogenesis in patients with TF.

PMID- 16456231
TI  - Recent developments in proteomics: implications for the study of cardiac
      hypertrophy and failure.
AB  - The key components to the molecular understanding of the pathophysiology of
      various forms of heart failure involve global and/or large-scale identifications
      of proteins, their patterns of expression, posttranslational modifications, and
      functional characterization. Particularly, proteins involved in the induction of
      cardiac (mal)adaptive hypertrophic growth, interstitial fibrosis, and contractile
      dysfunction are of interest. In general, with the accumulation of vast amounts of
      DNA sequences in databases, researchers have become aware that merely having
      complete sequences of genomes and transcriptional changes for thousands of genes
      simultaneously will not be sufficient to elucidate, in molecular terms, the
      etiology and pathophysiology of cardiovascular disease. In the last decade, a new
      technology called proteomics has become available that allows biological and
      (patho)physiological questions to be approached exclusively from the protein
      perspective. Proteomics may enable us to map the entire complement of proteins
      expressed by the heart at any time and condition. This approach creates the
      unique possibility to identify, by differential analysis, protein alterations
      associated with the etiology of heart disease and its progression, outcome, and
      response to therapy. To illustrate the true power of proteomics, most of the
      currently available methodologies are first reviewed, including their
      limitations. This review also deals with the current status and the perspectives
      of proteomics applications in research on heart failure in general. Furthermore,
      examples of our recent data on global protein profiling of the pressure
      overloaded rat right ventricle and of endothelin-1-stimulated cultures of
      neonatal rat cardiac myocytes are provided. The last section is devoted to the
      continuous advances in proteomic technologies, including protein separation
      methods, mass spectrometric instrumentation, computational analysis, and
      bioinformatic tools, together with integrative databases.

PMID- 16456234
TI  - G protein-linked cell signaling and cardiovascular functions in
      diabetes/hyperglycemia.
AB  - Vascular complications, including impaired contractility and increased cell
      proliferation, are the most common complications with diabetes. Chronic
      hyperglycemia seems to be an important contributing factor in this process.
      Various signaling pathways are implicated in diabetes/hyperglycemia-induced
      impaired vascular functions. Nonenzymatic glycation, enhanced production of
      diacylglycerol, increased activity of membranous protein kinase C (PKC), and
      increased oxidative stress have been proposed to explain the adverse effects of
      hyperglycemia on vascular smooth muscle cells. Hyperglycemia-induced stimulation
      of L-type Ca2+ channel via G protein-coupled adenylyl cyclase/cAMP and
      phospholipase C/PKC pathways also has been shown. In addition, hyperglycemia has
      been reported to decrease the availability of nitric oxide in humans, which may
      contribute to all the hemodynamic and physiological changes occurring in
      diabetes. G protein-adenylyl cyclase signaling that plays an important role in
      the regulation of cardiovascular functions also has been reported to be impaired
      in diabetes and under hyperglycemic conditions. In this review article, various G
      protein-linked cell signaling and functions in diabetes and hyperglycemia are
      discussed.

PMID- 16456233
TI  - Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth
      factor-angiogenesis and tyrosine kinase receptor Flk-1.
AB  - In our study, resveratrol (polyphenol) has been identified as a very important
      stimulus/agent for the induction of new vessel growth. Occlusion of a main
      coronary depletes the blood supply to the myocardium and subsequently reduces
      cardiac function, which ultimately leads to heart failure. Progressive, chronic
      coronary artery occlusion has been shown to induce development of collateral
      arteries to re-establish and maintain blood flow to the myocardium at risk via
      the growth of new capillary vessels or angiogenesis. Studies from our laboratory,
      as well as from others, have already confirmed the protective role of collaterals
      against myocardial ischemia and cell death. We have successfully demonstrated in
      rat myocardial infarction (MI) model an effect of resveratrol on significant
      upregulation of the protein expression profiles of vascular endothelial growth
      factor (VEGF) and its tyrosine kinase receptor Flk-1, 3 wk after MI. Pretreatment
      with resveratrol also increased nitric-oxide synthase (inducible NOS and
      endothelial NOS) along with increased antiapoptotic and proangiogenic factors
      nuclear factor (NF)-kappaB and specificity protein (SP)-1. We also were able to
      demonstrate increased capillary density as well as improved left ventricular
      function by pharmacological preconditioning with resveratrol 3 wk after MI.

PMID- 16456232
TI  - New strategies for cardiovascular gene therapy: regulatable pre-emptive
      expression of pro-angiogenic and antioxidant genes.
AB  - Cardiovascular diseases are among the major targets for gene therapy. Initially,
      clinical experiments of gene transfer of vascular endothelial growth factor
      (VEGF) improved vascularization and prevented the amputation in patients with
      critical leg ischemia. However, the majority of trials did not provide conclusive
      results and therefore further preclinical studies are required. Importantly, data
      indicate the necessity of regulated expression of angiogenic factors,
      particularly VEGF, to obtain the therapeutic effect. It is also suggested that
      the combined delivery of two or more genes may improve the formation of mature
      vasculature and therefore may be more effective in the amelioration of ischemia.
      Moreover, experimental approaches in animal models displayed the promise of gene
      transfer modulating the inflammatory processes and oxidant status of the cells.
      Particularly, the concept of preemptive gene therapy has been tested, and recent
      studies have demonstrated that overexpression of heme oxygenase-1 or
      extracellular superoxide dismutase can prevent heart injury by myocardial
      infarction induced several weeks after gene instillation. The combination of a
      preemptive strategy with regulated gene expression, using the vectors in which
      the therapeutic transgene is driven by exogenously or endogenously controllable
      promoter, offers another modality. However, we hypothesize that regulatable gene
      therapy, dependent on the activity of endogenous factors, might be prone to
      limitations owing to the potential disturbance in the expression of endogenous
      genes. Here, we demonstrated some indications of these drawbacks. Therefore, the
      final acceptance of these promising strategies for clinical trials requires
      careful validation in animal experiments.

PMID- 16456235
TI  - Peroxisome proliferator-activated receptor-gamma ligands attenuate brain
      natriuretic peptide production and affect remodeling in cardiac fibroblasts in
      reoxygenation after hypoxia.
AB  - Cardiac fibroblasts (CFs) participate in cardiac remodeling after hypoxic cardiac
      damage, and remodeling is thought to be mediated by CF synthesis of brain
      natriuretic peptide (BNP). It is unknown whether the peroxisome proliferator
      activated receptors (PPARs), which mediate cellular signaling for growth and
      migration, affect BNP synthesis and whether PPARs participate in regulation of
      extracellular matrix protein (ECM) expression for remodeling. We examined the
      production of BNP in cultured neonatal ventricular CFs and its signaling system
      on collagen synthesis and on activation of matrix metalloproteinases (MMPs) in
      reoxygenation after hypoxia. BNP mRNA was detected in CFs, and a specific BNP
      protein, BNP1-32, was secreted into the media. Abundance of collagen I and III
      was increased in the media at reoxygenation. mRNA and protein levels for MMP-2
      and the tissue inhibitor of metalloproteinase (TIMP)-1 were enhanced in CFs at
      reoxygenation. These observations also were noted in CFs after incubation with
      angiotensin II (10 microM) for 24 h. Pretreatment with pioglitaozone (0.1-10
      microM) attenuated BNP mRNA and protein abundance of collagen III, MMP-2, and
      TIMP-1 in CFs at reoxygenation. The secreted BNP was also decreased by
      pioglitaozone in the media. Furthermore, PPAR activators inhibited reoxygenation
      induced activation of nuclear factor (NF)-kappaB. These results demonstrate that
      PPAR activators inhibit BNP synthesis in CFs and imply that PPAR activators may
      regulate ECM remodeling partially through the NF-kappaB-mediated pathway.

PMID- 16456236
TI  - Insulin signal mimicry as a mechanism for the insulin-like effects of vanadium.
AB  - Among several metals, vanadium has emerged as an extremely potent agent with
      insulin-like properties. These insulin-like properties have been demonstrated in
      isolated cells, tissues, different animal models of type I and type II diabetes
      as well as a limited number of human subjects. Vanadium treatment has been found
      to improve abnormalities of carbohydrate and lipid metabolism and of gene
      expression in rodent models of diabetes. In isolated cells, it enhances glucose
      transport, glycogen and lipid synthesis, and inhibits gluconeogenesis and
      lipolysis. The molecular mechanism responsible for the insulin-like effects of
      vanadium compounds have been shown to involve the activation of several key
      components of insulin-signaling pathways that include the mitogen-activated
      protein kinases (MAPKs) extracellular signal-regulated kinase 1/2 (ERK1/2) and
      p38MAPK, and phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB). It is
      interesting that the vanadium effect on these signaling systems is independent of
      insulin receptor protein tyrosine kinase activity, but it is associated with
      enhanced tyrosine phosphorylation of insulin receptor substrate-1. These actions
      seem to be secondary to vanadium-induced inhibition of protein tyrosine
      phosphatases. Because MAPK and PI3-K/PKB pathways are implicated in mediating the
      mitogenic and metabolic effects of insulin, respectively, it is plausible that
      mimicry of these pathways by vanadium serves as a mechanism for its insulin-like
      responses.

PMID- 16456237
TI  - Altered chemokine receptor profile on circulating leukocytes in human heart
      failure.
AB  - Chemokines and their receptors have been implicated in the pathogenesis of
      different forms of heart failure (HF). We examined CC- and CXC-chemokine receptor
      expression in fresh peripheral blood leukocyte populations from 24 end-stage HF
      patients consisting of coronary artery disease (CAD; n = 6) and hypertrophic
      cardiomyopathy (HCM; n = 7) or idiopathic dilated cardiomyopathy (IDCM; n = 8) or
      valvular disease (VD; n = 3) and compared the data with 18 healthy controls.
      Levels of CCR1, 2, 3, 4, 5, and 7, and CXCR1, 2, 3, and 4 were measured by flow
      cytometry, and the expression profile was assessed as molecules of equivalent
      soluble fluorochrome units as well as frequency (percentage) of CD3+, CD4+, and
      CD8+ T cells and monocytes or granulocytes. Frequency of CD3+ CXCR4+, CD3+
      CXCR1+, and CD3+ CXCR3+ cells was significantly increased in HF patients, whereas
      only CCR7 and CXCR4 expression levels were elevated on CD3+ cells. Both CD4+
      CXCR4+ and CD8+ CXCR4+ cell frequencies were significantly increased irrespective
      of cardiac disease etiology. Elevated CCR7 expression was less pronounced on CD4+
      than CD8+ cells in patients with CAD and IDCM. Expression of CXCR4 on CD8+ cells
      was upregulated substantially, regardless of the cause of disease. CD8+ CXCR1+
      and CD8+ CXCR3+ but not CD4+ CXCR1+ or CD4+ CXCR3+ cells were increased in the HF
      patients with IDCM and CAD, respectively. Expression of CXCR1 or CXCR3 on both
      CD4+ and CD8+ cells did not differ in all the groups. For monocytes, frequency of
      CD14+ CCR1+ and CD14+ CCR2+ cells was significantly decreased in CAD patients,
      whereas, increase in CD14+ CXCR4+ cell frequency was accompanied with elevated
      CXCR4 expression. On granulocytes, CXCR1 and CXCR2 receptors were downregulated
      in all patients, compared with controls. Our results suggest that the altered
      expression profile of CC- and CXC-chemokine receptors on circulating leukocyte
      populations involves enhanced activation of the immune system, perhaps as part of
      the pathogenic mechanisms in HF. Modulation of the chemokine network could offer
      interesting novel therapeutic modalities for end-stage HF.

PMID- 16456238
TI  - Angiotensin preconditioning of the heart: evidence for redox signaling.
AB  - Angiotensin II (Ang II) has been found to exert preconditioning-like effect on
      mammalian hearts. Diverse mechanisms are known to exist to explain the
      cardioprotective abilities of Ang II preconditioning. The present study
      hypothesized, based on the recent report that Ang II generates reactive oxygen
      species (ROS) through NADPH oxidase, that Ang II preconditioning occurs through
      redox cycling. To test this hypothesis, a group of rat hearts was treated with
      Ang II in the absence or presence of an NADPH oxidase inhibitor, apocynin; or a
      cell-permeable ROS scavenger, N-acetyl cysteine (NAC). Ang II pretreatment
      improved postischemic ventricular recovery; reduced myocardial infarction; and
      decreased the number of cardiomyocyte apoptosis, indicating its ability to
      precondition the heart against ischemic injury. Both apocynin and NAC almost
      abolished the preconditioning ability of Ang II. Ang II resulted in increase in
      ROS activity in the heart, which was reduced by either NAC or apocynin. Ang II
      also increased both the NADPH oxidase subunits gp91 phox and p22phox mRNA
      expression, which was abolished with apocynin and NAC. Our results thus
      demonstrate that the Ang II preconditioning was associated with enhanced ROS
      activities and increased NADPH oxidase subunits p22phox and gp91phox expression.
      Both NAC and apocynin reduced ROS activities simultaneously abolishing
      preconditioning ability of Ang II, suggesting that Ang II preconditioning occurs
      through redox cycling. That both NAC and apocynin reduced ROS activities and
      abolished Ang II-mediated increase in p22phox and gp91phox activity further
      suggest that such redox cycling occurs via both NADPH oxidase-dependent and 
      independent pathways.

PMID- 16456239
TI  - Genetic deletion of fas receptors or Fas ligands does not reduce infarct size
      after acute global ischemia-reperfusion in isolated mouse heart.
AB  - Apoptosis has been shown in cardiac cells under divergent physiological and
      pathological conditions. However, there has been an ongoing debate upon the
      relative contribution of cardiomyocyte apoptosis to the myocardial infarct size
      after ischemia-reperfusion (I-R) injury. We tested the hypothesis that blocking
      the death receptor pathway of apoptosis through genetic deletion of Fas receptors
      or Fas ligands would reduce myocardial infarct size caused by acute I-R injury.
      The hearts isolated from Fas receptor or Fas ligand knockout (KO) mice as well as
      the C57BL/6J wild-type control mice (N = 6-8 per group) were subjected to 20 min
      of global ischemia and 30 min of reperfusion in Langendorff mode. Our results
      show that the infarct size, determined with triphenyltetrazolium chloride
      staining, was not significantly different between the three groups (i.e., 30.2 +/
      3.9% for wild-type controls, 30.0 +/- 2.1% for Fas ligand KOs, and 23.8 +/- 3.6%
      for Fas receptor KOs; mean +/- SEM, p > 0.05). Postischemic leakage of lactate
      dehydrogenase, another marker of necrotic cellular injury, also was not
      significantly different between these groups (p > 0.05). In addition,
      postischemic ventricular contractile function as well as coronary flow were
      similar for all the experimental groups (p > 0.05). In conclusion, contrary to
      our original hypothesis, the present study in the gene KO mice suggests that the
      Fas ligand- and Fas receptor-mediated death receptor pathway of apoptosis is not
      the primary determinant of myocardial infarct size and ventricular dysfunction
      caused by acute global I-R injury in the isolated perfused mouse heart.

PMID- 16456240
TI  - Structural adaptation in adult rabbit ventricular myocytes: influence of dynamic
      physical interaction with fibroblasts.
AB  - The mechanism of induction of cardiomyocyte (CM) dedifferentiation, as seen in
      chronic hibernating myocardium, is largely unknown. Recently, a cellular model
      was proposed consisting of long-term cocultures of adult rabbit CMs and cardiac
      fibroblasts in which typical structural characteristics of hibernation-like
      dedifferentiation could be induced. Only CMs in close contact with fibroblasts
      underwent these changes. In this study, we further investigated the
      characteristics of the fibroblast-CM interaction to seek for triggers and
      phenomena involved in CM dedifferentiation. Adult rabbit CMs were cocultured with
      cardiac or 3T3 fibroblasts. Heterocellular interactions and the structural
      adaptation of the CMs were quantified and studied with vital microscopy and
      electron microscopy. Immunocytochemical analysis of several adhesion molecules,
      i.e., N-cadherin, vinculin, beta1-integrin, and desmoplakin, were examined. Upon
      contact with CMs, fibroblasts attached firmly and pulled the former cells,
      resulting in anisotropic stretch. Quantification of the attachment sites revealed
      a predominant binding of the fibroblast to the distal ends of the CM in d 1
      cocultures and a shift towards the lateral sides of the CMs on d 2 of coculture,
      suggesting a redistribution of CM membrane proteins. Immunocytochemical analysis
      of cell adhesion proteins showed that these were upregulated at the
      heterocellular contact sites. Addition of autologous and nonautologous
      fibroblasts to the CM culture similarly induced a progressive and accelerated
      structural adaptation of the CM. Dynamic passive stretch invoked by the
      fibroblasts and/or intercellular communication involving cell adhesion molecule
      expression at the interaction sites may play an important role in the induction
      of hibernation-like dedifferentiation of the cocultured adult rabbit CMs.

PMID- 16456241
TI  - Allergic airway inflammation and beta-adrenoceptor dysfunction.
AB  - A reduced response to beta-adrenoceptor agonists has been reported in airways of
      asthmatic subjects. Mechanisms for beta-adrenoceptor dysfunction are (1)
      inactivation or downregulation of beta-adrenoceptors by specific agonists
      (homologous desensitization) or by inflammatory mediations (heterologous
      desensitization), (2) inactivation or downregulation of second messengers of beta
      adrenoceptor pathway. Studies from our laboratory have shown that allergen
      challenge of passively sensitized human bronchi causes a beta-adrenoceptor
      dysfunction as a result of reduced activity of the receptor-coupled Gs protein.
      The dysfunction was prevented by leukotriene-receptor antagonists or a cell
      membrane stabilizer, but not by an antihistimine or indomethacin, suggesting a
      central role of leukotrienes released from resident inflammatory cells in its
      genesis. Furthermore, the beta-adrenoceptor response and Gs protein function
      after allergen exposure were restored by short-term (3 h) incubation with
      beclomethasone dipropionate, suggesting an effect independent of gene
      transcription. Restoration of the intracellular beta-adrenoceptor effector
      pathway may contribute to the efficacy of corticosteroids in the acute treatment
      of asthma.

PMID- 16456242
TI  - Role of extracellular matrix and its regulators in human airway smooth muscle
      biology.
AB  - Altered extracellular matrix (ECM) deposition contributing to airway wall
      remodeling is an important feature of asthma and chronic obstructive pulmonary
      disease (COPD). The molecular mechanisms of this process are poorly understood.
      One of the key pathological features of these diseases is thickening of airway
      walls. This thickening is largely to the result of airway smooth muscle (ASM)
      cell hyperplasia and hypertrophy as well as increased deposition of ECM proteins
      such as collagens, elastin, laminin, and proteoglycans around the smooth muscle.
      Many growth factors and cytokines, including fibroblast growth factor (FGF)-1,
      FGF-2, and transforming growth factor (TGF)-beta1, that are released from the
      airway wall have the potential to contribute to airway remodeling, revealed by
      enhanced ASM proliferation and increased ECM protein deposition. TGF-beta1 and
      FGF-1 stimulate mRNA expression of collagen I and III in ASM cells, suggesting
      their role in the deposition of extracellular matrix proteins by ASM cells in the
      airways of patients with chronic lung diseases. Focus is now on the bidirectional
      relationship between ASM cells and the ECM. In addition to increased synthesis of
      ECM proteins, ASM cells can be involved in downregulation of matrix
      metalloproteinases (MMPs) and upregulation of tissue inhibitors of
      metalloproteinases (TIMPs), thus eventually contributing to the alteration in
      ECM. In turn, ECM proteins promote the survival, proliferation, cytokine
      synthesis, migration, and contraction of human airway smooth muscle cells. Thus,
      the intertwined relationship of ASM and ECM and their response to stimuli such as
      chronic inflammation in diseases such as asthma and COPD contribute to the
      remodeling seen in airways of patients with these diseases.

PMID- 16456243
TI  - Pulmonary hypertension in human newborns with congenital diaphragmatic hernia is
      associated with decreased vascular expression of nitric-oxide synthase.
AB  - The molecular basis of the pathogenesis of pulmonary hypertension (PH) associated
      with congenital diaphragmatic hernia (CDH) is poorly understood. Variation in
      responses to therapeutic strategies such as nitric oxide (NO) inhalation and
      extracorporeal membrane oxygenation (ECMO) in patients with CDH remains a major
      problem in pediatric critical care. We investigated the expression pattern of NO
      generating enzyme nitric-oxide synthase (NOS) (both endothelial [eNOS] and
      inducible [iNOS] isoforms) in the lungs of CDH patients with PH and evaluated the
      influence of ECMO on the expression levels of these genes in an attempt to
      understand the underlying molecular mechanisms. Lung autopsy specimens from 23
      cases of CDH not treated by ECMO and 10 ECMO-treated CDH cases were studied and
      compared with 11 age-matched controls. Expression of iNOS and eNOS was assessed
      by immunohistochemistry and video-image analysis. Expression of iNOS in the
      endothelium of small pulmonary arteries (external diameter < or =200 Mum) was
      significantly lower in CDH cases that had not received ECMO treatment (p = 0.04).
      ECMO-treated CDH cases did not differ from controls in iNOS expression. Alveolar
      macrophages (CD68+ cells), of which the number also was increased, showed
      significantly enhanced staining for iNOS in CDH cases (p = 0.03) compared with
      controls. The observed decrease in pulmonary expression of iNOS in patients with
      CDH suggests a potential role in the pathogenesis of pulmonary hypertension in
      newborns with CDH. ECMO treatment was correlated with induction of this enzyme,
      which may result in NO-mediated vasodilatation and thereby transiently reduce the
      pulmonary hypertension in CDH.

PMID- 16456244
TI  - Cytokines and vascular permeability: an in vitro study on human endothelial cells
      in relation to tumor necrosis factor-alpha-primed peripheral blood mononuclear
      cells.
AB  - Tumor response is strongly enhanced by addition of tumor necrosis factor (TNF)
      alpha to chemotherapy in local-regional perfusion. TNF primarily targets the
      endothelial lining of the tumor-associated vasculature, thereby improving
      permeability of the vascular bed. This augments uptake of the coadministered
      chemotherapeutic drug in the tumor. In vitro, however the high dose of TNF did
      not directly affect endothelial cells, indicating that other factors, most likely
      TNF-induced, are involved in the antivascular activities observed in vivo. This
      is supported by in vivo studies in our laboratory in which depletion of
      leukocytes resulted in loss of the antivascular activity of TNF. The present
      study examined the role of peripheral blood mononuclear cells (PBMCs) on
      endothelial cells by exposing them to TNF, interferon (IFN)-gamma, and PBMCs. We
      observed morphological changes of the endothelial cells when exposed to TNF in
      combination with IFN. Endothelial cells became elongated. and gaps between the
      cells formed. Addition of PBMCs enhanced these alterations. The endothelial layer
      became disrupted with highly irregular-shaped cells displaying large gap
      formations. PBMCs also contributed to an increased permeability of the
      endothelial layer without augmenting apoptosis. Replacing PBMC by interleukin
      (IL)-1beta produced similar effect with regard to inhibition of cell growth,
      morphological changes, and induction of apoptosis. Blocking IL-1beta with a
      neutralizing antibody diminished the effects inflicted of PBMCs. These
      observations indicate that endogenously produced IL-1beta by primed PBMCs plays
      an important role in the antivascular effect of TNF.

PMID- 16456246
TI  - Will India need inactivated poliovirus vaccine (IPV) to complete polio
      eradication?

PMID- 16456245
TI  - Cytogenetic and molecular analysis of male infertility: Y chromosome deletion
      during nonobstructive azoospermia and severe oligozoospermia.
AB  - Reduced male fertility and subfertility can be caused by genetic factors that
      affect both germ cell development, differentiation, and function; in particular,
      chromosome abnormalities and Yq microdeletions are a possible cause of
      spermatogenetic impairment in males as shown by their higher frequency in
      infertile men than in the general male population. Microdeletion of the long arm
      of the Y chromosome (Yq) are associated with spermatogenic failure and have been
      used to define three regions on Yq (AZFa, AZFb, and AZFc) that are critical for
      germ cell development. With the advent of assisted reproductive technology and
      intracytoplasmic sperm injection, knowledge about the various factors leading to
      spermatogenic impairment is one of the most important aspects of scientific
      research. Therefore, this study was designed to identify the frequency of
      cytogenetic and submicroscopic interstitial deletions in azoospermia factor loci
      in infertile Indian males. One hundred and eighty males with nonobstructive
      oligozoospermia and azoospermia were included in this study. Semen analysis was
      done in each case to determine the spermatogenic status. Individuals were
      subjected to detailed clinical examination, family history, and endocrinological
      and cytogenetic study after consent from the patient. Peripheral blood cultures
      were set up according to standard protocols and 30 G-banded metaphases were
      analyzed in each case. Numerical and structural chromosomal abnormalities were
      detected in 40 infertile cases. Fluorescence in situ hybridization analysis was
      done in some cases to identify the percentage of mosaic cell lines and any
      cryptic or low-level mosaicism. Polymerase chain reaction microdeletion analysis
      was done in 140 cytogenetically normal cases. Of the 140 cases, 8 showed deletion
      of at least one of the sequence-tagged site markers. Review of literature has
      shown that the overall frequency of microdeletions varies from 1 to 55%. In the
      present study, the frequency of microdeletion was 5.8%, and deletions were
      identified in cases with undescended testis and varicocele and cases with
      bilateral severe testiculopathy.

PMID- 16456247
TI  - Reducing amputations in 'at risk foot'.

PMID- 16456248
TI  - Irradiated blood components.

PMID- 16456249
TI  - Brucellosis in India: a deceptive infectious disease.
AB  - Brucellosis is an important but neglected disease in India. This zoonotic disease
      is present in all livestock systems and increased demand for dairy products
      accompanied with changing and intensified farming practices has raised the
      concern for increased spread and intensified transmission of this infection to
      the human population with increased risk of disease. Brucellosis can be
      controlled by mass vaccination of livestock. Human brucellosis can be treated
      with a combination of antibiotics but is very difficult to diagnose and requires
      laboratory testing for confirmation. Only a few recent studies have addressed the
      prevalence and importance of brucellosis as a human disease problem in India. The
      disease may be overlooked and misdiagnosed because of the difficult diagnosis and
      the absence and lack of experience with laboratory testing. Alertness of medical
      staff is needed to recognize and diagnose the disease. Awareness of risk groups
      is needed to take appropriate preventive measures and to accept control measures.

PMID- 16456250
TI  - Effect of pre-storage gamma irradiation on red blood cells.
AB  - BACKGROUND & OBJECTIVE: The irradiation of blood components has received
      increased attention due to increasing categories of patients eligible to receive
      such blood to prevent transfusion-associated graft versus host disease.
      Irradiation leads to enhancement of storage lesions, which could have deleterious
      effects when such blood is transfused. The aim of the present study was to assess
      the biochemical changes during conventional preservation of irradiated and non
      irradiated whole blood. METHODS: Ten units of whole blood were taken from healthy
      donors and divided into two parts. One aliquot was subjected to gamma irradiation
      and then stored under conventional blood banking conditions. Sampling was done
      from these irradiated and non-irradiated blood bags and tests for free plasma
      haemoglobin, plasma potassium and lactate dehydrogenase (LDH) were performed.
      RESULTS: A progressive increase in the mean values of plasma Hb, K+ and LDH was
      seen in both the groups. The increase was statistically significant.
      INTERPRETATION & CONCLUSION: Our findings indicated that the gamma irradiation of
      blood resulted in increased plasma haemoglobin, potassium and LDH. These
      biochemical changes might not have clinical significance when irradiated blood is
      transfused to a select group of patients. There is a need for further in vivo
      studies to follow up the consequences of transfusion of irradiated blood in
      patients.

PMID- 16456251
TI  - Precontrol observations on lymphatic filariasis & geo-helminthiases in two
      coastal districts of rural Orrisa.
AB  - BACKGROUND & OBJECTIVE: Lymphatic filariasis (LF) is a major public health
      problem in India, accounting for 40 per cent of the global burden. The World
      Health Organization has launched a global programme to eliminate LF by 2020 and
      India is a signatory to it. Orissa, an eastern Indian State has long been known
      to be endemic for LF. Prior to implementation of mass drug administration
      programme it is important to collect baseline data on filariasis and geo
      helminthiases in the State. The present cross-sectional survey was therefore
      carried out between February and December 2001 to obtain baseline information on
      both LF and geo-helminthiases before application of the control measures.
      METHODS: The study was carried out in rural areas of Puri and Ganjam districts in
      two phases. In phase I, the distribution of microfilaraemia in two district was
      mapped out in randomly selected primary health centres (PHCs), and 12
      microfilaraemic villages were identified in each district by cluster analysis for
      the phase II study. In phase II, detailed clinical and parasitological survey for
      LF and geo-helminthiases was carried out following the standard procedures.
      RESULTS: Wuchereria bancrofti was found to be widely prevalent in Puri district
      with certain pockets of Brugia malayi while W. bancrofti was the only species in
      Ganjam district. The microfilaraemia (Mf) rate was found to be 9.5 and 11.1 per
      cent; and circulating filarial antigenaemia (CFA) was 16.8 and 17.8 per cent in
      Puri and Ganjam respectively. The geometric mean intensity (GMI) of Mf per ml of
      blood among positive individuals was 387 in Puri and 454 in Ganjam. The overall
      disease rate in Puri was 7.9 and 8.9 per cent in Ganjam. The prevalence of
      chronic manifestations was found to be significantly higher (P<0.001) than the
      acute manifestations in both the districts. The prevalence of geo-helminthiases
      was 31.8 per cent in Puri and 42.1 per cent in Ganjam; and the heavy infection
      was found to be significantly higher (P<0.001) in Ganjam compared to Puri
      district. INTERPRETATION & CONCLUSION: The present study identified LF and geo
      helminthiases as widely distributed health problem in rural areas of coastal
      Orissa which warrants intervention measures along the lines recommended by the
      global programme for elimination of LF and geo-helminthiases to reduce the
      disease burden.

PMID- 16456252
TI  - Reliability and validity of the Malayalam hospital anxiety and depression scale
      (HADS) in cancer patients.
AB  - BACKGROUND & OBJECTIVE: The hospital anxiety and depression scale (HADS) has been
      widely used on cancer patients as an indicator of psychological morbidity. Though
      the scale has been used in India, no reports are available on translation of HADS
      in any Indian language and testing the reliability. The present study describes
      the translation process of HADS into Malayalam and testing its reliability and
      validity on psychological morbidity in cancer patients. METHODS: The English
      version of the HADS was translated into Malayalam and was used in this study. The
      questionnaire was administered to 240 cancer patients and statistical analysis
      was carried out using Chronbach's alpha to test the internal consistency of the
      HADS scale while confirmatory factor analysis was carried out using principal
      axis factoring with equimax rotation and Kaiser Normalization to test its
      construct validity. RESULTS: The Cronbach's alpha was found to be 0.81 for the
      HADS anxiety subscale, 0.71 for the HADS depression subscale, and 0.85 for HADS
      tool. Confirmatory factor analysis (CFA) indicated two depression items (i.e.,
      enjoyment and anhedonia) loading onto the anxiety subscale. Clinical caseness for
      anxiety was observed in 8 per cent, while 11 per cent of the patients had
      borderline mood disorder. Clinical caseness for depression was identified in 7.6
      and 13 per cent of patients were found to have borderline mood disturbances.
      INTERPRETATION & CONCLUSION: This preliminary validation study of the Malayalam
      version of the HADS showed it as an acceptable, and reliable measure of
      psychological morbidity among cancer patients. The prevalence of anxiety and
      depression in Indian population was low and enjoyment and anhedonia might present
      as anxiety initially.

PMID- 16456253
TI  - Prenatal diagnosis of phenylketonuria.
AB  - We report prenatal diagnosis of phenylketonuria by linkage analysis of the
      markers linked to the phenylalanine hydroxylase (PAH) gene. Three markers
      comprising STR (TCTAT)n in intron 3, VNTR (30bp long cassette) in the 3' UTR and
      Xmn1 RFLP were ascertained in the affected child, the parents and the chorionic
      villi sample. The foetus was confirmed to be heterozygous for the mutant allele.
      The diagnosis that the foetus was unaffected was confirmed by biochemical tests
      in the newborn.

PMID- 16456254
TI  - Outbreak of cholera in & around Chandigarh during two successive years (2002,
      2003).
AB  - BACKGROUND & OBJECTIVE: Outbreaks of cholera caused by Vibrio cholerae O1 Ogawa
      occurred in and around Chandigarh during two successive year 2002 and 2003. This
      study highlights the antibiotic sensitivity and phage typing pattern of V.
      cholerae isolates during 2002 and 2003. METHODS: Faecal specimens from acute
      gastroenteritis cases from July to September, 2002 and in the same month in 2003
      were collected. Isolation and identification of pathogen was done according to
      standard methodology. Simultaneously water samples from the areas reporting the
      maximum number of cholera cases were also processed. Antibiotic susceptibility
      pattern of the isolates was studied and isolates were sent to National Institute
      of Cholera and Enteric Diseases (NICED), Kolkata for confirmation and phage
      typing. RESULTS: Of the 156 patients in 2002 and 125 in 2003, 59 and 40 isolates
      respectively were found to be positive for V. cholerae O1 serotype Ogawa biotype
      El tor. Of the 45 water samples tested in 2002, eight were found to be positive
      for V. cholerae O1 serotype Ogawa biotype El tor. None of the 52 water samples
      tested in 2003 was found to be positive for V. cholerae. Phage type 27 was found
      to be the predominant type for both the years. Majority of the clinical isolates
      were found to be resistant to more than two drugs. INTERPRETATION & CONCLUSION:
      The drug resistance in V. cholerae was on the rise during the subsequent
      outbreak. Phage 27 remained the predominant type in both the years. The major
      reason for the outbreak was traced to be contaminated water of the hand pumps in
      the affected area. Continuous surveillance of the outbreak is necessary to
      contain the spread of transmission.

PMID- 16456255
TI  - Epidemiological investigation of nosocomial Acinetobacter infections using
      arbitrarily primed PCR & pulse field gel electrophoresis.
AB  - BACKGROUND & OBJECTIVE: Nosocomial infections caused by Acinetobacter spp. are a
      significant problem worldwide. Information on epidemiological investigation of
      outbreaks caused by Acinetobacter species in India is lacking. The present
      investigation was carried out to elucidate molecular epidemiology of
      Acinetobacter species isolated from nosocomial infections in a tertiary care
      hospital in south India using two DNA-based typing methods. METHODS: The medical
      records of 43 patients with Acinetobacter infection during a period of 24 months
      were reviewed and Acinetobacter isolates obtained from these patients were
      characterized phenotypically by assimilation tests and genotypically by
      arbitrarily primed PCR (AP-PCR) and pulse field gel electrophoresis (PFGE).
      Susceptibility testing results of the Acinetobacter isolates were also analysed.
      RESULTS: Most of the infections were nosocomial, and the majority of these were
      acquired in intensive care units (ICUs). A. baumannii accounted for 41.8 per cent
      (n=18) of all pneumonia acquired in the ICU. AP-PCR with M13 primer distinguished
      8 different PCR patterns comprising of 2 to 6 DNA fragments of 0.1 to 1.0 kb.
      PFGE identified 9 distinct profiles with five subvarients. By APPCR,
      epidemiologically unrelated strains could not be differentiated and often
      differences within biotypes of A. baumannii were not detectable. ApaI
      macrorestriction (PFGE) identified at least 4 outbreaks caused by 3 clones of A.
      baumannii and one clone of DNA group 13TU, one replacing the other in a well
      defined temporal order. INTERPRETATION & CONCLUSION: Most of A. baumannii
      isolates were multidrug resistant. PFGE was more discriminatory [Discriminatory
      Index (DI)=0.96 than AP-PCR fingerprinting (DI=0.88)] in the present study.
      However, AP-PCR fingerprinting is more useful as a simple and rapid
      identification technique for epidemiological investigation of nosocomial
      Acinetobacter infections.

PMID- 16456256
TI  - Iodine nutritional status & prevalence of goitre in Sundarban delta of South 24
      Parganas, West Bengal.
AB  - BACKGROUND & OBJECTIVE: In post salt iodization phase endemic goitre and
      associated iodine deficiency disorders (IDD) were found prevalent in a randomly
      selected rural area of Sundarban delta and its adjoining areas of West Bengal.
      The present investigation was thus undertaken to study the total goitre rate,
      urinary iodine and thiocyanate excretion pattern of the school going children,
      iodine content in edible salt and drinking water in the Sundarban delta of South
      24-Parganas in West Bengal. METHODS: A total of 4656 school children (6-12 yr)
      were clinically examined for goitre from 13 different areas in the delta region.
      Urinary iodine and thiocyanate levels were measured in 520 (40 from each area)
      samples collected randomly to evaluate the iodine nutritional status and
      consumption pattern of dietary goitrogen. Simultaneously iodine content was
      determined in 104 (8 from each area) drinking water samples and 455 (35 from each
      area) edible salt samples collected from the areas. RESULTS: Children of all the
      areas were affected by endemic goitre. The prevalence rates were in the ranges
      from 25-61 per cent; overall goitre prevalence was 38.2 per cent (grade 1--34.0%;
      grade 2--4.2%). Median urinary iodine level in the studied areas was 225 microg/l
      (range 115-525 microg/l) indicating no biochemical iodine deficiency in the
      region. Mean urinary thiocyanate levels were in the range from 0.326-1.004 mg/dl.
      Iodine content in drinking water samples were in the ranges from 22-119 microg/l,
      and 55.6 per cent edible salt samples had iodine level above the recommended 15
      ppm at the consumption point. INTERPRETATION & CONCLUSION: The severity of
      endemic goitre was high in the studied population though the iodine nutritional
      status was found satisfactory in the region indicating no biochemical iodine
      deficiency. The people of the region consumed iodine through iodized salt but
      about 44 per cent of the salt samples at household level contained inadequate
      iodine, however their iodine intake was compensated through iodine in water and
      food. They also consumed dietary goitrogen. Environmental factors other than
      iodine deficiency may have possible role for the persistence of endemic goitre in
      the region. More investigations are thus necessary to arrive at certain definite
      cause of high goitre rates in this population.

PMID- 16456257
TI  - Comparative in vitro activity of beta-lactam/beta-lactamase inhibitor
      combinations against gram negative bacteria.
AB  - BACKGROUND & OBJECTIVE: Currently, the use of beta-lactamase inhibitors in
      combination with beta-lactam antibiotics represents an effective measure to
      combat a specific resistance mechanism of beta-lactamase producing organisms.
      Knowledge about the susceptibility profile of bacteria to different combination
      agents available is essential to guide appropriate treatment of severe infections
      in hospitalized patients. The present study compares the in vitro activity of
      three commercially available beta-lactam/beta-lactamase inhibitor combinations
      (piperacillin/tazobactam, cefoperazone/sulbactam, ticarcillin/clavulanic acid)
      against beta-lactamase producing gram negative bacteria in a tertiary care
      hospital in north India. METHODS: A total of 9004 consecutively isolated extended
      spectrum beta-lactamase (ESBL) producing gram negative bacteria isolated from
      various clinical samples from patients admitted to the All India Institute of
      Medical Sciences, New Delhi, from September 2003 to August 2004 were included in
      the study. These isolates were screened for ESBL production by the inhibitor
      based test recommended by the National Committee for Clinical Laboratory
      Standards (NCCLS). Antibiotic susceptibility testing was carried out by disc
      diffusion method as per NCCLS guidelines. RESULTS: Of the 9004 isolates tested,
      3232 (35.89%) were sensitive and 568 (6.31%) were resistant to all three
      combination agents, and rest 5204 (57.80%) were resistant to at least one of the
      combinations. Susceptibility to piperacillin/tazobactam, cefoperazone/sulbactam,
      and ticarcillin/clavulanic acid was 81.37, 76.06 and 45.48 per cent respectively.
      Piperacillin/tazobactam exhibited significantly (P<0.05) greater antimicrobial
      activity against Pseudomonas spp., Escherichia coli and Klebsiella spp. compared
      to cefoperazone/sulbactam. INTERPRETATION & CONCLUSION: Overall
      piperacillin/tazobactam was observed to be the best combination agent followed by
      cefoperazone/sulbactam in our setting. This difference in activities of these
      combination agents needs to be evaluated further by ascertaining their efficacy
      in clinical studies.

PMID- 16456258
TI  - Use of methylation sensitive polymerase chain reaction for detection of fragile X
      full mutation & carrier state in males.
AB  - BACKGROUND & OBJECTIVE: Fragile X syndrome is the most common cause of inherited
      mental retardation. It is characterized by the progressive expansion of
      polymorphic (CGG) trinucleotide repeats located in the promoter region of the
      FMRI gene located at Xq27.3. The typical dysmorphic features that help in
      diagnosis are very often subtle or absent especially in pre-pubertal children.
      Confirmation is by molecular diagnosis based on repeat size and methylation
      analysis of the FMR1 gene. The present study was done to evaluate the utility of
      a methylation sensitive polymerase chain reaction (ms-PCR) method in the
      molecular diagnosis of fragile X syndrome in a select group of mentally retarded
      male children. METHODS: We used a methylation sensitive PCR technique, which
      initially modified DNA by bisulphite treatment. Two sets of PCR primers one each
      for methylated and unmethylated DNA sequences, were used. In full mutations, PCR
      specific for the methylated sequences was designed to amplify the CpG
      dinucleotide region upstream to the CGG repeats in clinically affected males. In
      healthy males and carriers, the second set of primers would amplify the
      unmethylated DNA sequences. The amplified PCR product size would help to
      differentiate between normal and premutation repeat size. RESULTS: In all, 25
      blood samples collected from mentally retarded male children and five from normal
      controls were tested. Analysis of cases revealed one full blown mutation and one
      carrier state. These were further confirmed by southern blotting. INTERPRETATION
      & CONCLUSION: Unlike currently used methods, methylation sensitive PCR is a quick
      and accurate technique which could be used for the rapid screening of fragile X
      syndrome in mental retardation.

PMID- 16456259
TI  - A preliminary investigation of genomic screening in cervical carcinoma by
      comparative genomic hybridization.
AB  - BACKGROUND & OBJECTIVE: Available clinical, radiological and histopathologic risk
      factors are not adequate for accurate prognosis in uterine cervix carcinoma.
      Hence there is a need to identify indicators to select high risk cases. Most
      cancers occur and progress through step-wise somatic genetic mutations. Thus
      screening of whole genome for specific genomic alterations and its outcome
      following treatment may predict prognosis. The present study was carried out to
      investigate genomic alterations associated with cervical carcinoma and any
      association of genomic alterations with clinico-pathologic parameters. METHODS:
      Cervical carcinoma cases (n = 4) were subjected to protocol based clinical
      evaluation, treatment and follow up as a double blind procedure. Tumour samples
      were collected before radiotherapy and 3 months after completion of radiotherapy.
      All the samples were stored at -80 degrees C. Comparative genomic hybridization
      (CGH) was carried out to screen genomic alterations in all tumour samples
      obtained before treatment. Conventional fluorescent in situ hybridization (FISH)
      was carried out to confirm the CGH findings and to follow up post-treatment
      samples. Patients were followed up for a minimum of one year or until death.
      RESULTS: The CGH analysis identified genomic losses and gains. The gains were
      observed mainly in chromosomes 1q 25.1, 3q 26.1, 6q 13-16, 9p 22 and X, and
      losses in chromosome 10 and 11q21-24. CGH and FISH results were complementary to
      each other. Of the four patients, two were alive and two were dead at the end of
      follow up. INTERPRETATION & CONCLUSION: Initial results indicated that
      persistence of genomic alterations and appearance of giant nucleus was associated
      with poor prognosis and the same may be used to follow up patient. Similar
      studies on large sample with longer period of follow up are warranted to validate
      our result.

PMID- 16456260
TI  - Seroprevalence of HIV infection among the foreign students at Agra during a
      fifteen year period (1988-2002).
AB  - The present study reports a retrospective analysis of data of HIV testing of
      foreign students from Sub-Saharan Africa, South-East Asia and Europe, studying as
      well as staying at Agra, over a period of 15 yr (1988 to 2002). Of the 2653 [2092
      (78.85%) were from the Sub-Saharan African countries, 377 (14.21%) from the South
      East Asian countries, and 184 (6.93%) from the European countries], foreign
      students tested for HIV, only 26 were found to be positive for HIV-1/2 antibodies
      by the ELISA, rapid and Western Blot assays. Out of 26 HIV-positive, 17 males and
      7 females were from Sub-Saharan Africa and 2 males were from the European
      countries. The range of HIV-positivity over a period of 15 yr varied greatly.
      When the five-year (1988-1992, 1993-1997 and 1998-2002) results were compared,
      the HIV-seropositivity showed a decline from 1.85, 0.50 to 0.36 per cent in the
      first, second and third 5 yr slots, respectively. While the data were not
      representative of all foreign students in India, this reflected the population
      tested in this centre was not a growing focus of HIV infection in this part of
      the country.

PMID- 16456261
TI  - Chronic kidney disease: a missing component of integrated control of non
      communicable diseases.

PMID- 16456262
TI  - A new whitlockite, Ca8.42Na1.16V(PO4)7.
AB  - Single crystals of a new complex phosphate, calcium sodium vanadium phosphate,
      Ca8.42Na1.16V(PO4)7, have been grown from a melt under an inert atmosphere. The
      crystal structure has rhombohedral (R3c) symmetry and belongs to the whitlockite
      structure type. Vanadium(III) ions occupy nearly regular octahedral sites (M5
      with 3 point symmetry), which share corners with six PO4 tetrahedra to form
      isolated units. The calcium ions occupy eight- and nine-coordinated sites. The
      sodium ions partially occupy one octahedral position and share one nine
      coordinated position with a Ca atom.

PMID- 16456263
TI  - MoCu3TeO7Cl2.0.5H2O.
AB  - Single crystals of molybdenum(VI) tricopper(II) tellurium(IV) heptaoxide
      dichloride hemihydrate, MoCu3TeO7Cl2.0.5H2O, were synthesized via a transport
      reaction in sealed evacuated silica tubes. All atoms occupy general positions
      within the triclinic (P1) unit cell. The building units are irregular CuO4Cl and
      CuO3Cl2 square pyramids, distorted TeO3+1E trigonal bipyramids (E is the lone
      pair of TeIV) and irregular MoO5 pyramids. The TeO3+1E, CuO4Cl and CuO3Cl2
      polyhedra form (110) layers bridged by Mo atoms. The water molecules are located
      in [100] channels.

PMID- 16456264
TI  - Cation distribution in the zirconium chloride cluster phase Cs[(Zr6C)Cl15].
AB  - Poly[caesium [[mu6-carbido-dodecakis-mu2-chloro-hexazirconium]-tri-mu2-chloro]],
      Cs[(Zr6C)Cl15], crystallizes in the orthorhombic space group Pmma. The structure
      is built up of two symmetry-independent [(Zr6C)Cl(i)12Cl(a)6/2] cluster units
      (where ;inner' and ;outer' ligands are denoted by i and a, respectively), which
      are three-dimensionally connected to form a cluster network through all six
      halogen atoms on the exo positions of each octahedral (Zr6C) metal unit, forming
      Cl(a-a) bridges. The caesium cations are distributed in several voids within the
      cluster network. 16 of the 23 independent atoms lie on crystallographic special
      positions.

PMID- 16456265
TI  - A mixed-valence diacetate-bridged Mn(II)-Mn(III) complex incorporating a bridging
      phenolate ligand.
AB  - The synthesis and characterization of a new unsymmetrical dinucleating N,O-donor
      ligand, 2-[N,N-bis(2-pyridylmethyl)aminomethyl]-6-[N-(3,5-di-tert-butyl-2
      oxidobenzyl)-N-(2-pyridylamino)aminomethyl]-4-methylphenol (H2Ldtb), as well as
      the X-ray crystal structure of its corresponding mixed-valence diacetate-bridged
      manganese complex, di-mu-acetato-mu-{2-[N,N-bis(2-pyridylmethyl)aminomethyl]-6-[N
      (3,5-di-tert-butyl-2-oxidobenzyl)-N-(2-pyridylamino)aminomethyl]-4
      methylphenolato}dimanganese(II,III) tetraphenylborate,
      [MnIIMnIII(C42H49N5O2)(C2H3O2)2](C24H20B), are reported. The complex may be
      regarded as an interesting structural model for the mixed-valence MnII-MnIII
      state of manganese catalase.

PMID- 16456266
TI  - Bis[bis(3-phenylpyrazol-1-yl)(pyrazol-1-yl)methane]copper(II) bis(perchlorate)
      acetonitrile disolvate.
AB  - The title copper(II) complex, [Cu(C22H18N6)2](ClO4)2.2C2H3N, comprises two
      neutral substituted tris(pyrazol-1-yl)methane ligands bonded to a central Cu(II)
      ion, which is positioned on a crystallographic inversion center. Six Cu-N bonds
      are arranged in a distorted octahedral fashion. The unsubstituted pyrazole rings
      on each ligand are oriented trans with respect to each other, interdigitated with
      the two 3-phenylpyrazole rings of the other ligand.

PMID- 16456267
TI  - A one-dimensional iodine-bridged Pt(II)/Pt(IV) mixed-valence complex, catena
      poly[[[bis(ethylenediamine)platinum(II)]-mu-iodo
      [bis(ethylenediamine)platinum(IV)]-mu-iodo] hydrogenphosphate dihydrogenphosphate
      iodide trihydrate].
AB  - The title compound, {[PtIIPtIVI2(C2H8N2)4](HPO4)(H2PO4)I.3H2O}n, has a chain
      structure composed of square-planar [Pt(en)2]2+ and elongated octahedral trans
      [PtI2(en)2]2+ cations (en is ethylenediamine) stacked alternately along the c
      axis and bridged by the I atoms; a three-dimensionally valence-ordered system
      exists with respect to the Pt sites. The title compound also has a unique cyclic
      tetramer structure composed of two hydrogenphosphate and two dihydrogenphosphate
      ions connected by strong hydrogen bonds [O...O = 2.522 (10), 2.567 (10) and 2.569
      (11) A]. The Pt and I atoms form a zigzag ...I-PtIV-I...PtII... chain, with PtIV
      I bond distances of 2.6997 (7) and 2.6921 (7) A, interatomic PtII...I distances
      of 3.3239 (8) and 3.2902 (7) A, and PtIV-I...PtII angles of 154.52 (3) and 163.64
      (3) degrees . The structural parameters indicating the mixed-valence state of
      platinum, expressed by delta = (PtIV-I)/(PtII-I), are 0.812 and 0.818 for the two
      independent I atoms.

PMID- 16456268
TI  - Disodium 2,5-bis(phenylamino)terephthalate decahydrate, an intermediate in the
      industrial synthesis of quinacridone pigments.
AB  - The title compound, 2Na+.C20H14N2O4(2-).10H2O, is an intermediate in the
      industrial synthesis of red and violet quinacridone pigments. The structure is
      remarkable for two reasons. First, one of the Na+ ions is surrounded octahedrally
      by five water molecules and a phenyl group, although the crystal contains many
      more water molecules than are required for complete coordination of both Na+ ions
      with six water molecules each. Secondly, although the anion has almost exact
      molecular inversion symmetry, it is positioned on a general position; this is one
      of the very few exceptions to the observation of Kitajgorodskij [Advances in
      Structure Research by Diffraction Methods--Fortschritte der Strukturforschung mit
      Beugungsmethoden (1970), Vol. 3, pp. 173-247] that molecules with inversion
      centres always lie on crystallographic inversion centres.

PMID- 16456269
TI  - A novel three-dimensional cadmium(II) coordination polymer incorporating 1,4
      bis(1,2,4-triazol-1-ylmethyl)benzene and thiocyanate.
AB  - In the title complex, poly[cadmiumII-mu2-1,4-bis(1,2,4-triazol-1-ylmethyl)benzene
      di-mu2-thiocyanato], [Cd(NCS)2(C12H12N6)]n, the CdII atom lies on an inversion
      centre in a distorted octahedral environment. Four N atoms from the thiocyanate
      and 1,4-bis(1,2,4-triazol-1-ylmethyl)benzene (bbtz) ligands occupy the equatorial
      positions, and two S atoms from symmetry-related thiocyanate ligands occupy the
      axial positions. The benzene ring of the bbtz ligand lies about an inversion
      centre. Single thiocyanate bridges link the CdII atoms into two-dimensional
      sheets containing novel 16-membered [Cd4(mu-NCS-N:S)4] rings. The bbtz ligands
      further link these two-dimensional sheets into an unprecedented covalent three
      dimensional network for the cadmium-thiocyanate system.

PMID- 16456270
TI  - Bis{[phthalocyaninato(2-)]arsenic(III)} octaiododiarsenic(III).
AB  - Crystals of the novel title arsenic(III)-phthalocyanine complex,
      [As(C32H16N8)]2[As2I8] or [AsPc]2[As2I8], where Pc is the phthalocyaninate(2-)
      macrocycle, have been obtained from the reaction of pure powdered arsenic with
      phthalonitrile under oxidizing conditions (iodine vapour) at 463 K. The crystals
      are formed by separate but interacting [AsPc]+ cations and centrosymmetric
      [As2I8]2- anions. The As atom of the [AsPc]+ ion is bonded to the four isoindole
      N atoms of the Pc macrocycle and lies 0.762 (1) A out of their plane. The anionic
      part of the complex consists of two [AsI4]- units joined together into a
      centrosymmetric [As2I8]2- counter-ion. The arrangement of oppositely charged
      moieties, viz. [AsPc]+ and [As2I8]2-, in the crystal structure is determined
      mainly by their ionic attractions and by pi-pi interactions between the aromatic
      phthalocyaninate(2-) macrocycles.

PMID- 16456272
TI  - Tris(1,10-phenanthroline)copper(II) di-mu-iodo-bis(diiodomercurate) dimethyl
      sulfoxide monohydrate.
AB  - In the cationic complex present in the title compound,
      [Cu(C12H8N2)3][Hg2I6].C2H6OS.H2O, the copper(II) center adopts a highly distorted
      octahedral geometry, ligated by the six N atoms of three 1,10-phenanthroline
      ligands. The structure includes an iodide-bridged dimeric mercurate anion for
      neutrality and uncoordinated dimethyl sulfoxide and water molecules.

PMID- 16456271
TI  - A novel nickel(II) coordination polymer incorporating 1,4-phenylenediacetic acid
      and 1,10-phenanthroline.
AB  - The title nickel(II) coordination polymer, viz. poly[[bis(1,10
      phenanthroline)tris(mu3-1,4-phenylenediacetato)trinickel(II)] dihydrate],
      {[Ni3(C10H8O4)3(C12H8N2)2].2H2O}(n), consists of linear trinuclear building
      blocks with two crystallographically unique Ni atoms. One Ni(II) atom and the
      geometric centre of one 1,4-phenylenediacetate ligand in the trinuclear unit both
      lie on inversion centres, while the other unique Ni(II) atom lies near the
      inversion centre, together with another 1,4-phenylenediacetate ligand. Each pair
      of adjacent trinuclear units is bridged by 1,4-phenylenediacetate ligands,
      forming two kinds of infinite chains along the a and b axes, respectively. These
      two kinds of chains crosslink to yield a two-dimensional network in the ab plane.
      The two-dimensional sheets further stack along the c axis via pi-pi stacking
      interactions and hydrogen bonds, forming a three-dimensional supramolecular
      structure.

PMID- 16456273
TI  - Dichloro(1,2-dimethoxyethane)bis(tosylimido)molybdenum(VI), a versatile nitrene
      transfer reagent.
AB  - In the title compound, [Mo(C7H7NO2S)2Cl2(C4H10O2)], the Mo-Cl bond lengths are
      2.3730 (8) and 2.3842 (8) A, the former being the shortest within the series of
      analogous structurally characterized bis(imido) Mo complexes. This fact clearly
      explains the very strong Lewis acidity of the metal centre in this complex and,
      as a result, its synthetic versatility as a nitrene transfer reagent towards
      different phosphanes and strained cycloolefins.

PMID- 16456274
TI  - Two one-dimensional zinc(II) coordination polymers: catena-poly[[bis(pentane-2,4
      dionato-kappa2O,O')zinc]-mu-1,4-bis(x-pyridyl)-2,3-diazabuta-1,3-diene] (x = 3,
      4).
AB  - The structures of the two title isomeric compounds, [Zn(C5H7O2)2(C12H10N4)]n, are
      built up around two non-equivalent symmetry centres, one of them at the cation
      position and the other bisecting the N-N bond in the 1,4-bis(3/4-pyridyl)-2,3
      diazabuta-1,3-diene (3pdb/4pdb) units. Both Zn cations have the Zn atoms an
      inversion centres and present tetragonally distorted octahedral environments, but
      differences in their linkage through the 3pdb and 4pdb ligands give rise to
      differently shaped weakly interacting chains.

PMID- 16456275
TI  - Tetrapiperidinium di-mu-methoxy-di-mu5-oxo-tetra-mu3-oxo-dodeca-mu2-oxo
      octaoxodecavanadate.
AB  - The structure of the title compound, (C5H12N)4[V10O26(CH3O)2], reveals the
      presence of four protonated piperidinium cations and a [{V10O26}(OCH3)2]4-
      polyanion having an embedded centre of inversion. The compound is distinguished
      by presenting, in contrast with other anionic decavanadates, two methoxy groups
      bridging the outermost V atoms, and it becomes the first example of this type
      among reported decavanadates.

PMID- 16456277
TI  - Bis(mu-diphenylphosphinato-kappa2O:O')bis[aqua(diphenylphosphinato
      kappaO)bis(pyridine-kappaN)cobalt(II)].
AB  - In the centrosymmetric title compound, [Co2(C12H10O2P)4(C5H5N)4(H2O)2], each
      approximately octahedral Co atom features two trans-coordinated pyridine
      molecules, one water molecule, a terminally coordinated monodentate
      diphenylphosphinate ligand, and two bidentate diphenylphosphinate ligands that
      bridge the two Co atoms across a centre of inversion to form a dimeric binuclear
      complex. The discrete molecules are linked by double hydrogen bonds between the
      terminally coordinated diphenylphosphinate ligand and the water molecule to form
      a continuous chain along the crystallographic b axis.

PMID- 16456276
TI  - Insights into crystallization mechanism: a synchrotron study of polymorphism in a
      cobalt acetate cluster compound.
AB  - The structure of the title compound, di-mu3-acetato
      1kappa2O,O':2kappaO';2kappaO:3kappa2O,O'-di-mu2-acetato
      1kappaO:2kappaO';2kappaO:3kappaO'-octapyridyl-1kappa3N,2kappa2N,3kappa3N
      tricobalt(II) bis(hexafluorophosphate), [Co3(C2H3O2)4(C5H5N)8](PF6)2, consists of
      divalent multinuclear cations in which three CoII ions are bridged by four mu2
      acetate groups. The CoII ions are arranged in an approximately linear manner. The
      bridging acetates adopt two distinct coordination geometries: one pair bridges
      via a single O atom and the other pair employs both O atoms. The coordination
      octahedron around each CoII ion is completed by three pyridine molecules for the
      two outer CoII ions and by two for the inner ion. Charge is balanced by two PF6-
      anions. Single-crystal synchrotron X-ray studies indicate the existence of two
      polymorphs, both triclinic, which are distinguished primarily by differences in
      the relative orientations of the multinuclear cations, which in form 1 are tilted
      with respect to each other, but in form 2 are co-parallel as a result of the
      central Co atom lying on an inversion centre. The results of the structural
      studies allow an insight into the crystallization mechanism and resultant
      polymorphism. They suggest that a (bidentate carboxyl)C-O...H-C(pyridine)
      interaction exists in solution. For form 1, crystallized from pyridine, the
      interaction is not structure determining, as it is satisfied by interactions
      between solvent and solute. For form 2, crystallized from CH2Cl2, the interaction
      is between a bound acetate carboxyl group on one cation and a bound pyridine on
      another and is thus structure directing.

PMID- 16456278
TI  - Cadmium nitrate coordination polymers with substituted pyridazino[4,5
      d]pyridazines.
AB  - catena-Poly[[aquabis(nitrato-kappa2O,O')cadmium(II)]-mu-1,2,3,6,7,8
      hexahydrocinnolino[5,4,3-cde]cinnoline-kappaN1:kappaN6],
      [Cd(NO3)2(C12H12N4)(H2O)]n, (I), and catena-poly[[[bis(nitrato
      kappa2O,O')cadmium(II)]-mu-2,2,7,7-tetramethyl-1,2,3,6,7,8
      hexahydrocinnolino[5,4,3-cde]cinnoline-kappaN1:kappaN6] chloroform solvate],
      {[Cd(NO2)2(C12H12N4)].CHCl3}n, (II), are the first structurally examined cadmium
      pyridazine coordination compounds. They possess one-dimensional polymeric
      structures supported by the bidentate bridging function of the cinnolino[5,4,3
      cde]cinnoline ligands, which lie about inversion centres. The Cd atoms are seven
      coordinated in (I) and six-coordinated in (II), involving two bidentate nitrate
      groups [Cd-O = 2.229 (2)-2.657 (2) A], two N atoms of the cinnoline ligands [Cd-N
      = 2.252 (2)-2.425 (2) A], and, additionally, a water O atom in (I) [Cd-O = 2.284
      (2) A]. In (I), the coordinated organic and aqua ligands form an intramolecular O
      H...N hydrogen bond [O...N = 2.730 (3) A].

PMID- 16456279
TI  - Dichloro[(3,5-dimethyl-1H-pyrazol-1-yl)methane]zinc(II) and di-mu-chloro
      bis{chloro[(3,5-dimethyl-1H-pyrazol-1-yl)methane]cadmium(II)}.
AB  - The Zn atom in dichloro[(3,5-dimethyl-1H-pyrazol-1-yl)methane]zinc(II),
      [ZnCl2(C11H16N4)], (I), is tetrahedrally coordinated by two N atoms from one
      bis(3,5-dimethylpyrazolyl)methane ligand and two terminal Cl atoms. The molecule
      has no crystallographic symmetry. One H atom of the CH2 group of the bis(3,5
      dimethylpyrazolyl)methane ligand interacts with a Cl atom of an adjacent molecule
      to yield intermolecular C-H...Cl contacts, thereby forming a one-dimensional
      zigzag chain extending along the b axis. On the other hand, in di-mu-chloro
      bis{chloro[(3,5-dimethyl-1H-pyrazol-1-yl)methane]cadmium(II)},
      [Cd2Cl4(C11H16N4)2], (II), each of the two crystallographically equivalent Cd
      atoms is pentacoordinated by two N atoms from one bis(3,5
      dimethylpyrazolyl)methane ligand, and by one terminal and two bridging Cl-
      anions. The molecule has a crystallographic centre of symmetry located at the mid
      point of the Cd...Cd line. One H atom of the CH2 group of the bis(3,5
      dimethylpyrazolyl)methane ligand interacts with a Cl atom of an adjacent molecule
      to produce pairwise intermolecular C-H...Cl contacts, thereby affording chains of
      molecules running along the c axis.

PMID- 16456280
TI  - A cobalt(III) compound of a 13-membered cyclic tetraamine: trans-(12,12-dimethyl
      1,4,7,10-tetraazacyclotetradecane)diisothiocyanatocobalt(III)
      tetraisothiocyanatozinc(II) ethanol solvate.
AB  - The title compound, [Co(NCS)2(C11H26N4)]2[Zn(NCS)4].C2H5OH, has two similar
      cations with the Co(III) atom coordinated in a planar fashion by the 13-membered
      cyclic tetraamine, in the 1R,4S,7R,10S configuration, and with trans
      isothiocyanate ligands. The six-membered chelate ring is in a chair conformation,
      with one axially and one equatorially oriented methyl substituent [mean Co-N =
      1.948 (2) A]. The ;opposite' chelate ring (N4 and N7) is in an eclipsed
      conformation [mean Co-N = 1.928 (2) A], and the ;side' chelate rings have gauche
      conformations. The mean Co-N(NCS) distance is 1.928 (2) A. Both cations have one
      Co-N-C group nearly linear and the other appreciably bent, with mean Co-N-C
      angles of 178.7 (1) and 160.4 (1) degrees , respectively. The [Zn(NCS)4]2- anion
      is approximately tetrahedral, with Zn-N = 1.951 (1)-1.986 (1) A, N-Zn-N = 104.5
      (1)-111.9 (1) degrees and Zn-N-C = 152.5 (1)-179.4 (1) degrees. One NH group is
      hydrogen bonded to the ethanol O atom and the other NH groups are bonded to
      thiocyanate S atoms, forming a network.

PMID- 16456281
TI  - The absolute configuration of (2S,4S)- and (2R,4R)-2-tert-butyl-4-methyl-3-(4
      tolylsulfonyl)-1,3-oxazolidine-4-carbaldehyde.
AB  - The title enantiomorphic compounds, C16H23NO4S, have been obtained in an
      enantiomerically pure form by crystallization from a diastereomeric mixture
      either of (2S,4S)- and (2R,4S)- or of (2R,4R)- and (2S,4R)-2-tert-butyl-4-methyl
      3-(4-tolylsulfonyl)-1,3-oxazolidine-4-carbaldehyde. These mixtures were prepared
      by an aziridination rearrangement process starting with (S)- or (R)-2-tert-butyl
      5-methyl-4H-1,3-dioxine. The crystal structures indicate an envelope conformation
      of the oxazolidine moiety for both compounds.

PMID- 16456282
TI  - A zwitterion of 1,5-bis(2-hydroxybenzamido)-3-azapentane: a two-dimensional
      hydrogen-bonding network involving dimers.
AB  - The title compound, 2-{N-[2-(2
      hydroxybenzamido)ethylammonioethyl]aminocarbonyl}phenolate, C18H21N3O4,
      crystallizes in a zwitterionic form as a result of intermolecular proton transfer
      and possesses a negatively charged phenolate group and a protonated amino group.
      The 2-hydroxybenzamide and 2-(aminocarbonyl)phenolate moieties attached to the
      two ends of the C-C-N-C-C backbone adopt a cis conformation in relation to this
      backbone. All N- and O-bound H atoms are involved in hydrogen-bond formation; the
      zwitterions are first linked into head-to-tail dimers, which are further
      organized into a two-dimensional network parallel to the crystallographic bc
      plane.

PMID- 16456283
TI  - Hydrogen-bonding patterns in trimethoprim picolinate and 2-amino-4,6
      dimethylpyrimidinium picolinate hemihydrate.
AB  - In the title compounds, namely 2,4-diamino-5-[(3,4,5
      trimethoxyphenyl)methyl]pyrimidin-1-ium pyridine-2-carboxylate,
      C14H19N4O3+.C6H4NO2-, (I), and 2-amino-4,6-dimethylpyrimidin-1-ium pyridine-2
      carboxylate hemihydrate, C6H10N3+.C6H4NO2-.0.5H2O, (II), the trimethoprim and 2
      amino-4,6-dimethylpyrimidin-1-ium cations are protonated at one of the pyrimidine
      N atoms. In (I), bifurcated hydrogen bonds are observed between a picolinate O
      atom, the protonated N atom and the 2-amino group; the graph-set designator is
      R2(1)(6). The pyrimidine moieties of the trimethoprim cations are
      centrosymmetrically paired through a pair of N-H...N hydrogen bonds. In addition
      to the base pairing, one of the picolinate O atoms bridges the 2- and 4-amino
      groups on either side of the paired bases, resulting in a complementary DADA
      array. In (II), the carboxylate group of the picolinate anion binds with the
      protonated pyrimidine N atom and the 2-amino group of the pyrimidine moiety
      through a pair of N-H...O hydrogen bonds, leading to the common ring motif
      R2(2)(8). The water molecule, which resides on a twofold rotation axis, bridges
      the carboxylate group of the picolinate anion via O-H...O hydrogen bonds.

PMID- 16456284
TI  - Three 4-aminoquinolines of antimalarial interest.
AB  - The structures of three compounds with potential antimalarial activity are
      reported. In N,N-diethyl-N'-(7-iodoquinolin-4-yl)ethane-1,2-diamine, C15H20IN3,
      (I), the molecules are linked into ribbons by N-H...N and C-H...N hydrogen bonds.
      In N-(7-bromoquinolin-4-yl)-N',N'-diethylethane-1,2-diamine dihydrate,
      C15H20BrN3.2H2O, (II), two aminoquinoline molecules and four water molecules form
      an R5(4)(13) hydrogen-bonded ring which links to its neighbours to form a T5(2)
      one-dimensional infinite tape with pendant hydrogen bonds to the aminoquinolines.
      The phosphate salt 7-chloro-4-[2-(diethylammonio)ethylamino]quinolinium
      bis(dihydrogenphosphate) phosphoric acid, C15H22ClN3(2+).2H2PO4-.H3PO4, (III),
      was prepared in order to establish the protonation sites of these compounds. The
      phosphate ions form a two-dimensional hydrogen-bonded sheet, while the
      aminoquinoline cations are linked to the phosphates by N-H...O hydrogen bonds
      from each of their three N atoms. While the conformation of the quinoline region
      hardly varies between (I), (II) and (III), the amino side chain is much more
      flexible and adopts a significantly different conformation in each case. Aromatic
      pi-pi stacking interactions are the only supramolecular interactions seen in all
      three structures.

PMID- 16456285
TI  - Hydrogen bonding and pi-pi stacking in 7-{2-[4-(4-methoxyphenyl)piperazin-1
      yl]ethoxy}-4-methyl-2H-chromen-2-one monohydrate.
AB  - In the title compound, C23H26N2O4.H2O, the benzopyran ring system is planar. The
      piperazine ring adopts an almost perfect chair conformation, and the methoxy
      group is coplanar with its parent benzene ring. Hydrogen bonds link two water
      molecules and two piperazine molecules into tetrameric units. The adjacent
      benzopyran moieties within these units also interact via pi-pi stacking
      interactions, and a sheet is formed by the propagation of these interactions. The
      bioassay results have shown alpha1-adrenoceptor antagonistic activity through in
      vitro animal experiments.

PMID- 16456286
TI  - An azo dye molecule having a pyridine-2,6-dione backbone.
AB  - The title azo dye, 2-(2-methoxyethoxy)ethyl 4-[(5-cyano-1-ethyl-4-methyl-2,6
      dioxo-1,2,3,6-tetrahydropyridin-3-ylidene)hydrazino]benzoate, C21H24N4O6, with a
      1-ethyl-5-cyano-2-hydroxy-4-methyl-6-pyridone component, crystallizes in the
      hydrazone form. Hydrogen bonding mediates the formation of four-molecule
      aggregates, which are further grouped into an extended structure by pi-pi
      stacking interactions between the aromatic rings of adjacent molecules, with a
      centroid-centroid separation of 3.697 (2) A.

PMID- 16456287
TI  - Three-in-one: the novel packing and structures of three independent molecules of
      a tricyclic boron compound.
AB  - The three independent molecules in a single crystal of the tricyclic compound 15
      [3-(dimethylamino)propoxy]-5,5,13,13-tetramethyl-1,7,9,14,16-pentaoxa-5,13
      diazonia-15-bora-6,8-diboratadispiro[5.1.5.3]hexadecane, C15H36B3N3O6, are bound
      in dense layers by C-H...O(B) intermolecular interactions. The 3
      (dimethylamino)propoxy arms adopt three different conformations with only van der
      Waals contact distances between the layers. The replicated differences in the B-N
      bond lengths [mean 1.723 (7) and 1.678 (5) A] for equivalent geometries are
      addressed using density functional theory (DFT) calculations.

PMID- 16456288
TI  - Naphthalene-1,3-diol.
AB  - The molecules of the title compound, C10H8O2, are linked by two O-H...O hydrogen
      bonds, which form infinite chains with a graph-set descriptor of C6. These chains
      are linked into puckered (100) sheets of R4(4)(8) and R4(4)(24) rings. Adjacent
      sheets are connected by weak C-H...pi and pi-pi interactions into a continuous
      three-dimensional network.

PMID- 16456289
TI  - Glycinium trichloroacetate.
AB  - The title compound, C2H6NO2+.C2Cl3O2-, crystallizes in the P4(1) space group with
      two glycinium cations and two trichloroacetate anions in the asymmetric unit. The
      glycinium cations have nearly Cs point-group symmetry which is only broken by the
      H atoms of the amine group. The trichloroacetate anions show typical bond lengths
      and angles, one of the trichloromethyl groups being disordered. Chains of
      alternating anions and cations run along the c axis. Within these chains,
      consecutive anion-cation pairs are bound via strong hydrogen bonds involving the
      carboxylate anions and the carboxyl or amine groups of the cations. Weaker
      hydrogen bonds bind neighbouring chains together.

PMID- 16456290
TI  - Tris(methylammonium) hydrogenphosphate dihydrogenphosphate.
AB  - The title compound, 3CH6N+.HPO4(2-).H2PO4-, aggregates with the moieties
      interconnected by O-H...O and N-H...O hydrogen bonds, with O...O and N...O
      distances in the ranges 2.5366 (16)-2.5785 (14) and 2.7437 (16)-2.9967 (18) A,
      respectively. Three C-H...O hydrogen bonds are also present, with C...O distances
      in the range 3.2310 (18)-3.3345 (17) A. All H atoms are ordered. Structures with
      ordered hydrogenphosphate and dihydrogenphosphate components are rare.

PMID- 16456291
TI  - An oximino tautomer of 1-n-decyl-4-hydroxyimino-3-methyl-1H-pyrazol-5(4H)-one.
AB  - The title compound, C14H25N3O2, consists of a five-membered heterocyclic ring to
      which a pendant decyl group is attached. The oximino tautomeric character of the
      molecule is clearly defined by the distribution of well defined double bonds in
      the heterocycle region (one C=O and two C=N). The most conspicuous packing
      interaction is the strong intermolecular hydrogen bond linking the oximino OH
      group and the carbonyl O atom to define broad planar hydrophilic strips running
      along the unique b axis. The alkyl chains adopt a fully extended conformation and
      lie almost at right angles to these one-dimensional structures, defining their
      hydrophobic counterpart.

PMID- 16456292
TI  - N8-(2'-O-methylribofuranosyl)-8-aza-7-deazaadenine monohydrate.
AB  - In the title compound, 4-amino-2-(2-O-methyl-beta-D-ribofuranosyl)-2H
      pyrazolo[3,4-d]pyrimidine monohydrate, C11H15N5O4.H2O, the conformation of the N
      glycosylic bond is syn [chi = 20.1 (2) degrees ]. The ribofuranose moiety shows a
      C3'-endo (3T2) sugar puckering (N-type sugar), and the conformation at the
      exocyclic C4'-C5' bond is -ap (trans). The nucleobases are stacked head-to-head.
      The three-dimensional packing of the crystal structure is stabilized by hydrogen
      bonds between the 2'-O-methylribonucleosides and the solvent molecules.

PMID- 16456293
TI  - Methyl 4-O-beta-L-galactopyranosyl-beta-D-glucopyranoside (methyl beta-L
      lactoside).
AB  - Methyl beta-L-lactoside, C13H24O11, (II), is described by glycosidic torsion
      angles phi (O5Gal-C1Gal-O4Glc-C4Glc) and psi (C1Gal-O1Gal-C4Glc-C5Glc) of 93.89
      (13) and -127.43 (13) degrees , respectively, where the ring atom numbering
      conforms to the convention in which C1 is the anomeric C atom and C6 is the
      exocyclic hydroxymethyl (CH2OH) C atom in both residues (Gal is galactose and Glc
      is glucose). Substitution of L-Gal for D-Gal in the biologically relevant
      disaccharide, methyl beta-lactoside [Stenutz, Shang & Serianni (1999). Acta
      Cryst. C55, 1719-1721], (I), significantly alters the glycosidic linkage
      interface. In the crystal structure of (I), one inter-residue (intramolecular)
      hydrogen bond is observed between atoms H3OGlc and O5Gal. In contrast, in the
      crystal structure of (II), inter-residue hydrogen bonds are observed between
      atoms H6OGlc and O5Gal, H6OGlc and O6Gal, and H3OGlc and O2Gal, with H6OGlc
      serving as a donor with two intramolecular acceptors.

PMID- 16456294
TI  - 7-Hydroxy-6-methoxy-3-[(2-oxo-2H-1-benzopyran-7-yl)oxy]-2H-1-benzopyran-2-one.
AB  - The title compound, daphnoretin, C19H12O7, was isolated from the leaves of
      Stellera chamaejasme L. Two independent molecules are present in the asymmetric
      unit, with similar conformations. Each of the independent molecules is composed
      of two chromene systems connected by an ether bridge. The dihedral angles between
      the mean planes of the two chromene systems are 86.9 (2) and 81.9 (3) degrees.
      Molecules form chains via hydrogen bonds and adjacent chains are parallel to each
      other.

PMID- 16456295
TI  - Hydrogen bonding in meso-4,5-diphenyl-3,6-diazaoctane-1,8-diol: the formation of
      one-dimensional linear chains of edge-fused rings.
AB  - The molecule of the title compound, C18H24N2O2, resides on a crystallographic
      inversion centre. The molecule adopts a transoid conformation with respect to the
      central C-C single bond and is in the meso form. A polarimetric study of the
      compound did not show any optical activity, indicating that the compound is a
      racemic mixture entirely consistent with the centrosymmetric C2/c space group. In
      the molecule, there is one intramolecular N-H...O interaction, resulting in the
      formation of a five-membered ring. In the crystal structure, intermolecular O
      H...N and C-H...O interactions are also observed. These interactions form an
      R2(2)(9) ring and one-dimensional linear chains of edge-fused rings running
      parallel to the [010] direction, which stabilize the crystal packing.

PMID- 16456296
TI  - (2RS,5SR,6SR)-methyl 4-{cis-2-[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran
      4-yl)phenoxymethyl]-6-hydroxy-3-phenylmorpholino}benzenesulfinate.
AB  - The title compound, C30H34FNO7S, is a key intermediate in the design of dual 5
      LOX (5-lipoxygenase)/COX-2 (cyclooxygenase-2) inhibitors. The compound
      crystallizes as a racemate. Linear hydrogen-bonded chains are aligned along the
      [201] direction, and stacked pi-pi interactions and C-H...O contacts stabilize
      the crystal structure.

PMID- 16456297
TI  - 2,2,4,4-Tetra-tert-butyl-1,3,5,2,4-benzotrioxadisilepine-7-carbaldehyde.
AB  - The molecule of the title compound, C23H40O4Si2, features an approximate non
      crystallographic C2 symmetry axis. The aldehyde group is disordered over two
      positions with similar occupancies. The geometry of the isolated molecule was
      studied by ab initio quantum mechanical calculations employing a molecular
      orbital Hartree-Fock method. The calculations reproduce well the equilibrium
      geometry but slightly overestimate the value of the Si-O bond lengths of the
      trioxadisilepine ring.

PMID- 16456298
TI  - (+/-)-1-Methyl-1,3,6-triphenyl-7-(2-phenylpropenyl)-1,2-dihydronaphthalene.
AB  - The crystal structure of the title compound, C38H32, presents a novel framework
      that combines the functionalities of a 1,6-diarene-substituted 1,2
      dihydronaphthalene (DHN) with a 1,4-distyrylbenzene (DSB) to form a crossed bis
      diarene. The lamellar crystal structure is held together by arene-arene
      interactions. While the orientations of the phenyl rings of the DSB units
      alternate within both the R and the S substructures, the homochiral substructures
      feature opposing polarity along the long axes of the DHN-based diarenes.

PMID- 16456300
TI  - The readers' corner. What services do you outsource, and why?

PMID- 16456299
TI  - The readers' corner. Which media do you use to train new chairside assistants?

PMID- 16456301
TI  - A cutting-wire system for removal of indirect bonding trays.

PMID- 16456302
TI  - Fiber-reinforced composites in lingual orthodontics.

PMID- 16456304
TI  - 2005 JCO Orthodontic Practice Study. Part 2. Practice success.

PMID- 16456305
TI  - Bite jumping with the Functional Mandibular Advancer.

PMID- 16456306
TI  - An in vivo evaluation of bond failure rates with hydrophilic and self-etching
      primer systems.

PMID- 16456307
TI  - Ponseti management of clubfoot in older infants.
AB  - Treatment of clubfoot with the Ponseti method is successful when performed
      immediately after birth. We treated 23 infants (36 feet) who presented to us
      after casting, applied at other institutions, failed or after 3 months of age.
      Twenty-two infants had serial casting started during the first 2 months, and one
      infant who was 6 months old at presentation had not received previous treatment.
      The original orthopaedists of 18 patients advised posteromedial release. The
      parameter studied was the need for posteromedial release (ie, failure of Ponseti
      casting and percutaneous Achilles tenotomy to obtain satisfactory clinical
      appearance). Only one (2.8%) of 36 feet required open surgical release (posterior
      only). Thirty-five feet required percutaneous Achilles tenotomy. A mean of six
      Ponseti casts were applied before tenotomy. Two feet (two infants) required
      anterior tibialis transfer for mild relapse; three other feet (two infants)
      required repeat casting for mild relapse. Most pediatric orthopaedists think that
      successful clubfoot casting depends on treatment started immediately after birth.
      Our data suggest that older infants with clubfoot can be treated successfully
      without extensive surgery. Our results in older infants are similar to the
      results of a previous study we conducted with younger infants. In that study, one
      (2.9%) of 34 feet required posteromedial release surgery. LEVEL OF EVIDENCE:
      Therapeutic study, Level IV (Case series). See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 16456308
TI  - Targeting rheumatoid tenosynovial angiogenesis with cytokine inhibitors.
AB  - Proliferation and invasion of the tenosynovial lining of tendons in patients with
      rheumatoid arthritis can result in tendon damage and rupture, leading to
      decreased hand function. Angiogenesis is an important process in rheumatoid joint
      disease; however, the role of angiogenesis in tendon disease is unknown. Our aim
      was to determine whether rheumatoid tenosynovial lining could produce angiogenic
      proteins, and if inhibition of tumor necrosis factor-alpha and interleukin-1
      could decrease vascular endothelial growth factor production. Samples of
      encapsulating and invasive tenosynovial lining taken from the same hand and wrist
      synovial lining were harvested from 58 patients with rheumatoid arthritis having
      wrist surgery. Ex vivo samples were studied to quantify vascularity, angiogenic
      protein production under normoxic and hypoxic conditions, and the effect of
      inhibiting tumor necrosis factor-alpha and interleukin-1 on vascular endothelial
      growth factor production. Rheumatoid tenosynovial lining was more vascular than
      rheumatoid joint synovial lining and produced high levels of angiogenic factors
      such as vascular endothelial growth factor, interleukin-1beta, fibroblast growth
      factor-2, and angiopoietin-2. Hypoxia induced an increase in production of
      vascular endothelial growth factor by ex vivo tenosynovial lining cells.
      Inhibition of the cytokines interleukin-1 and tumor necrosis factor-alpha
      effectively reduced vascular endothelial growth factor production by tenosynovial
      samples. LEVEL OF EVIDENCE: Therapeutic study. Level II (Prospective comparative
      study). See the Guidelines for Authors for a complete description of levels of
      evidence.

PMID- 16456309
TI  - Comparison of six radiographic projections to assess femoral head/neck
      asphericity.
AB  - Early radiographic detection of femoroacetabular impingement might prevent
      initiation and progression of osteoarthritis. The structural abnormality in
      femoral-induced femoroacetabular impingement (cam type) is frequently asphericity
      at the anterosuperior head/neck contour. To determine which of six radiographic
      projections (anteroposterior, Dunn, Dunn/45 degrees flexion, cross-table/15
      degrees internal rotation, cross-table/neutral rotation, and cross-table/15
      degrees external rotation) best identifies femoral head/neck asphericity, we
      studied 21 desiccated femurs; 11 with an aspherical femoral head/neck contour and
      10 with a spherical femoral head/neck contour. To radiographically quantify
      femoral head asphericity, we measured the angle where the femoral head/neck
      leaves sphericity (angle alpha). The aspherical femoral head/neck contours had a
      greater maximum angle alpha (70 degrees ) compared with the spherical head/neck
      contours (50 degrees ). The angle alpha varied depending on the radiographic
      projection: it was greatest in the Dunn view with 45 degrees hip flexion (71
      degrees +/- 10 degrees ) and least in the cross-table view in 15 degrees external
      rotation (51 degrees +/- 7 degrees ). Diagnosis of a pathologic femoral head/neck
      contour depends on the radiologic projection. The Dunn view in 45 degrees or 90
      degrees flexion or a cross-table projection in internal rotation best show
      femoral head/neck asphericity, whereas anteroposterior or externally rotated
      cross-table views are likely to miss asphericity. LEVEL OF EVIDENCE: Prognostic
      study, level II-1 (retrospective study).

PMID- 16456310
TI  - Three-year results of proximal tibia fractures treated with the LISS.
AB  - Proximal tibia fractures present a difficult treatment challenge with
      historically high complication rates. In a prospective study, we asked whether
      the Less Invasive Stabilization System (LISS) plate can adequately treat
      extraarticular and complex intraarticular proximal tibia fractures and provide
      low complication rates and acceptable long-term functional outcomes. We
      prospectively observed 25 patients with 26 proximal tibia fractures (AO type A2,
      A3, C1, C2, or C3) treated with the LISS. Consecutive 3-year followup included
      radiographs and clinical examinations using Knee Society scores and Hospital for
      Special Surgery scores for extraarticular and intraarticular fractures. No loss
      of reduction occurred in patients with extraarticular fractures, whereas varus
      malalignment occurred in one patient with an intraarticular fracture. Two
      patients with AO 41 C 3.3 fractures had severe knee arthrosis develop and had
      total knee replacements. The mean Knee Society scores and final average Hospital
      for Special Surgery scores were similar for extraarticular and intraarticular
      fractures. Complications related to the surgery included one delayed union and
      implant removal in two patients. The LISS provided stable fixation of
      extraarticular and intraarticular proximal tibia fractures and good functional
      outcomes with a low complication rate. In complex articular fractures additional
      screws should be used. LEVEL OF EVIDENCE: Therapeutic study, Level II (lesser
      quality randomized controlled trial [eg, < 80% followup, no blinding, or improper
      randomization]).

PMID- 16456311
TI  - The Wiltse paraspinal approach to the lumbar spine revisited: an anatomic study.
AB  - The paraspinal posterior approach to the lumbar spine initially was described for
      spinal fusion, particularly for treatment of lumbosacral spondylolisthesis.
      Despite the technical details described by Wiltse et al, the exact location of
      the sacrospinalis muscle that must be split remains unclear. We sought to clarify
      the anatomic description of the paraspinal posterior approach to the lumbar
      spine, and to provide topographic landmarks for facilitating this surgical
      approach. Fifty cadavers were dissected using an anatomic transmuscular
      paraspinal approach. The level of the natural cleavage plane between the
      multifidus and the longissimus parts of the sacrospinalis muscle was noted, and
      measurements were taken between this level and the midline at the level of the
      spinous process of L4. A natural cleavage plane between the multifidus and the
      longissimus parts of the sacrospinalis muscle was present in all specimens. There
      was a fibrous separation between the two muscular parts in 88 of 100 cases. The
      mean distance between the level of the cleavage plane and the midline was 4.04 cm
      (range, 2.4-7 cm). Small arteries and veins were present at the level of the
      cleavage plane in all specimens. These vascular landmarks make it easier to
      locate the muscular cleavage plane and reach the articular and transverse
      processes during the paraspinal approach.

PMID- 16456312
TI  - Static magnetic fields up-regulate osteoblast maturity by affecting local
      differentiation factors.
AB  - Cell culture studies have shown that static magnetic fields induce osteoblastic
      differentiation at an early stage. However, the mechanisms of differentiated
      effects have not been well described. We postulated that static magnetic fields
      stimulate osteoblastic differentiation by regulating early local factors released
      by the cells. To examine our hypothesis, MG63 osteoblast-like cells were exposed
      continuously to 0.4-T static magnetic fields for 12, 24, 48, and 72 hours. The
      morphologic changes and matrix vesicles release were observed by scanning and
      transmission electron microscopy. The effects of static magnetic fields on levels
      of transforming growth factor-beta1, Type I collagen, osteopontin, and alkaline
      phosphatase were compared between the exposed and unexposed cells. The data
      suggest MG63 cells treated with static magnetic fields have more differentiated
      morphologic features. The local regulatory factors produced by static magnetic
      field-treated cells were greater than those of the control cultures. These
      findings provide evidence that static magnetic fields affect osteoblastic
      maturation by up-regulating early local factors.

PMID- 16456313
TI  - A mobile-bearing knee prosthesis can reduce strain at the proximal tibia.
AB  - Mobile and fixed-bearing knee prostheses are likely to generate distinct strain
      gradients in the proximal tibia. The resulting strain distribution in the
      proximal tibia governs bone remodeling and affects implant integration and
      stability. We determined the effects of fixed and mobile-bearing total knee
      prostheses on strain distribution at the proximal tibia. This mobile-bearing
      prosthesis was evaluated in cadaveric specimens under axial and torsional
      loading. Strain on the proximal tibial cortex was measured with rosette strain
      gages and an optical full-field strain acquisition system. Tibial torsion in
      response to combined axial and torsional loading was documented. There was no
      difference in cortex strain between the fixed and the mobile-bearing prostheses
      under 1.5 kN axial loading. Superimposing 10 degrees tibial internal rotation
      induced 22% less compressive strain in the mobile-bearing prosthesis compared
      with the fixed-bearing prosthesis. Under 10 degrees tibial external rotation, the
      mobile-bearing prosthesis induced 33% less compressive strain than the fixed
      bearing prosthesis. Optically acquired strain fields showed peak compressive
      strain at the anteromedial aspect 30 mm below the joint line. The mobile-bearing
      prosthesis reduced torque in the proximal tibia during knee rotation by 68-73%
      compared with the fixed-bearing prosthesis. Our data suggest that the particular
      mobile-bearing prosthesis tested potentially reduces elevated strain levels in
      the proximal tibia.

PMID- 16456315
TI  - Accuracy of Ein Bild Rontgen Analyse in determining wear in total hip
      arthroplasty in vitro.
AB  - The Ein Bild Rontgen Analyse system is used to radiographically measure femoral
      head penetration in total hip replacement components. Because determining the
      accuracy of any wear analysis system is more precise and comparable under in
      vitro conditions, we used a femoral head migration simulator to assess the
      accuracy of Ein Bild Rontgen Analyse and determine the effect of magnification
      factors on accuracy. We used onscreen magnifications of 100% and 200% to measure
      anteroposterior radiographs, which improved the accuracy of determining femoral
      head penetration. Improvements averaged 0.056 mm (95% CI +/- 0.013 mm) in the X
      direction and 0.024 mm (95% CI +/- 0.027 mm) in the Y direction. Femoral head
      penetration was simulated in 0.25-mm steps from 0-1 mm. Accuracy ranged from 0
      0.029 mm (95% CI, 0.035-0.067 mm) for the X direction and from 0.001-0.013 mm
      (95% CI, 0.046-0.079 mm) for the Y direction. Assuming the worst accuracy
      combined for the X and Y directions, Ein Bild Rontgen Analyse can accurately
      detect femoral head penetration greater than 0.128 mm. These results are
      comparable with reported accuracy values for different systems and suggest that
      magnification tools should be considered with Ein Bild Rontgen Analyse when
      measuring wear radiographically.

PMID- 16456316
TI  - Postoperative rehabilitation protocols for Achilles tendon ruptures: a meta
      analysis.
AB  - The optimal postoperative rehabilitation protocol after surgical repair of an
      Achilles tendon rupture is unknown. Although a 6-week cast immobilization is
      common, many early functional rehabilitation protocols have been implemented. The
      purpose of this study was to conduct a meta-analysis to determine if an early
      functional protocol for surgical repair of an acute Achilles tendon rupture
      improves subjective patient satisfaction without an increase in rerupture rates.
      Secondary outcomes of interest from an early functional protocol include
      infections, range of motion, strength, and minor complications. An extensive
      literature search for randomized or quasirandomized studies identified six trials
      involving 315 patients. Early functional treatment protocols, when compared with
      postoperative immobilization, led to more excellent rated subjective responses
      and no difference in rerupture rate. Our conclusions are based on six trials with
      small sample sizes, and larger randomized trials are required to confirm these
      results. LEVEL OF EVIDENCE: Therapeutic Study, Level II (Systematic review of
      Level II studies or Level I studies with inconsistent results).

PMID- 16456317
TI  - Spindle cell predominant trichodiscoma: a fibrofolliculoma/trichodiscoma variant
      considered formerly to be a neurofollicular hamartoma: a clinicopathological and
      immunohistochemical analysis of 17 cases.
AB  - Seventeen solitary nasal tumors that fulfilled all diagnostic criteria of so
      called neurofollicular hamartoma, apart from distinct S100-positivity, were
      compared histopathologically and immunohistochemically with seven typical
      trichodiscomas from a similar clinical setting. Both the S100-negative
      neurofollicular hamartoma-like tumors and the trichodiscomas expressed an
      identical CD13-positive/CD34-positive fibrocytic immunophenotype without co
      expression of neural/perineural (S100, neurofilament, epithelial membrane
      antigen), myogenic (desmin, calponin, muscle-specific actin, and alpha-smooth
      muscle actin), or melanocytic (S100, HMB45, NKI/C3, MelanA) epitopes.
      Histopathologically, there was striking morphologic overlap between trichodiscoma
      and S100-negative neurofollicular hamartoma-like tumor, apart from a highly
      characteristic fascicularly organized cellular fibrocytic stroma in the latter.
      We conclude that fibrofolliculoma/trichodiscoma and neurofollicular hamartoma
      like tumor are morphologic variants of a single hamartomatous entity in which
      neurofollicular hamartoma-like tumor occupies the cellular pole of the
      morphologic spectrum. The entity formerly known as neurofollicular hamartoma
      appears to be nothing but a particularly cellular trichodiscoma with a
      distinctively organized stroma composed of CD34-positive fibrocytes. We therefore
      propose the new term spindle cell predominant trichodiscoma (SCPT) for this
      particular variant of the morphologic fibrofolliculoma/trichodiscoma spectrum.

PMID- 16456318
TI  - Rimming of adipocytes by neoplastic lymphocytes: a histopathologic feature not
      restricted to subcutaneous T-cell lymphoma.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell
      lymphoma of the skin presenting with histopathologic features simulating those of
      a lobular panniculitis. The presence of neoplastic T-lymphocytes forming a rim
      around the individual fat cells in the subcutaneous lobules, so-called "rimming"
      of adipocytes, is considered a characteristic morphologic feature of this type of
      cutaneous lymphoma. In this study we reviewed a series of 45 biopsy specimens of
      primary and secondary cutaneous B- and T-cell lymphomas and one of myeloid
      leukemia involving the subcutaneous tissues and showing rimming of adipocytes
      (subcutaneous panniculitis-like T-cell lymphoma: n = 16; mycosis fungoides, tumor
      stage: n = 3; aggressive epidermotropic CD8(+) T-cell lymphoma: n = 2; cutaneous
      gamma/delta T-cell lymphoma: n = 4; extranodal NK/T-cell lymphoma, nasal type: n
      = 4; cutaneous medium-large pleomorphic T-cell lymphoma, NOS: n = 5;
      CD4(+)/CD56(+) hematodermic neoplasm (blastic NK-cell lymphoma): n = 7; secondary
      cutaneous large B-cell lymphoma: n = 3; secondary cutaneous lymphoplasmacytic
      lymphoma: n = 1; specific cutaneous manifestations of acute myelogenous leukemia:
      n = 1). We could demonstrate that rimming of adipocytes by neoplastic cells can
      be recognized not only in subcutaneous panniculitis-like T-cell lymphoma, but
      also in several different entities of malignant lymphoma with skin involvement.
      Precise classification of cases with prominent involvement of the subcutaneous
      tissues can only be achieved upon precise correlation of clinicopathologic and
      phenotypic features. Rimming of adipocytes should not be considered specific of
      subcutaneous panniculitis-like T-cell lymphoma.

PMID- 16456319
TI  - Structural correlations between dermoscopic features of cutaneous melanomas and
      histopathology using transverse sections.
AB  - Interpretation of dermoscopic features of cutaneous melanoma is based on
      histologic description of perpendicular sections of the lesions that does not
      reflect the overview achieved by epiluminescence. We describe the utilization of
      transverse sections as a tool to define the histopathology of features that are
      the dermoscopic hallmarks of cutaneous melanoma. From a collection of 23
      pigmented lesions with the dermoscopic diagnosis of cutaneous melanoma submitted
      for surgical excision we selected, from each specimen, one dermoscopic feature
      (black dots and globules, brown dots, blues dots and globules, depigmentation,
      broadened network, radial streams or pseudopods) that was sampled with a 4-mm
      punch (specimen) to obtain perpendicular and transverse sections. Using this
      strategy, it was possible to correlate the histopathology of all features that
      are often used as criteria for diagnostic dermoscopy. The black dots were
      pigmented neoplastic cells at the dermal-epidermal junction (DEJ) and within the
      epidermis in heavily pigmented columns. Similar findings were seen in brown dots,
      however there was slightly less pigment. No statistical difference was observed
      between brown dots and black dots regarding size, area and number of atypical
      cellnests. Blue dots correlated to melanophages, surrounding the superficial
      vascular plexus. Depigmentation was characterized by intense fibrosis of the
      papillary dermis. The pigmented network showed atypical pigmented or non
      pigmented melanocytes at the DEJ and epidermis as well as heavily pigmented
      keratinocytes in the basal cell layer. The radial streaming and pseudopods had
      neoplastic cells in nests, a stratified growth pattern arranged in centrifugal
      linear extensions, resembling a arborescent branching. The results represented
      herein, are an important tool for understanding histopathological alterations
      responsible for dermoscopic features and for improving the efficacy of this
      diagnostic method.

PMID- 16456320
TI  - Early acral melanoma in situ: correlation between the parallel ridge pattern on
      dermoscopy and microscopic features.
AB  - In non-white populations, acral skin is the most prevalent site of malignant
      melanoma. Early melanomas of this anatomic site are often misdiagnosed as
      melanocytic nevi, which are not uncommon on acral skin. In fact, clinical and/or
      histopathological features of melanocytic nevi occasionally mimic those of early
      acral melanoma and vice versa, and thus differentiation of early acral melanoma
      from melanocytic nevus is sometimes very difficult for clinicians as well as for
      histopathologists. Our dermoscopic investigation has revealed that the parallel
      ridge pattern, a band-like pigmentation on the ridges of the skin markings, is
      highly specific to malignant melanoma in situ on acral volar skin. In the present
      study, we reviewed 22 acral melanocytic lesions that showed the parallel ridge
      pattern on dermoscopy but had very subtle clinical and/or histopathological
      presentations. We diagnosed 20 of them as early melanoma in situ by careful
      histopathological examination, which revealed histopathological features very
      similar to those seen in macular portions of overt acral melanoma, but
      fundamentally different from features found in melanocytic nevi on acral skin. In
      correspondence with their dermoscopic pattern, in these early lesions of acral
      melanomas, proliferation of solitary arranged melanocytes was mainly detected in
      the crista profunda intermedia, the epidermal rete ridge underlying the ridge of
      the skin marking. The two remaining lesions were diagnosed as possible cases of
      acquired melanocytic nevus because of the formation of well-demarcated nests of
      melanocytes in the epidermal rete ridges. We propose that a finding of
      preferential proliferation of solitary arranged melanocytes in the crista
      profunda intermedia is an important clue for the histopathological diagnosis of
      early phases of acral melanoma.

PMID- 16456321
TI  - Spindle cell lipoma of the oral cavity.
AB  - Spindle cell lipoma is typically seen in the neck/trunk region of middle-aged and
      older men. Rare cases of oral spindle cell lipoma have been reported. An entity
      described as myxoid lipoma of the oral cavity has rarely been reported but
      appears to be more properly classified as spindle cell lipoma. We describe the
      largest series yet of oral spindle cell lipoma involving the tongue (4), buccal
      mucosa (1), floor of mouth (1), and lip (1). The patients (3M; 4F) ranged from 31
      to 88 years old. All presented with mass lesions. All were circumscribed and
      composed of mature adipocytes admixed with bland spindled cells. In two cases the
      adipocytes appeared atrophic, imparting a pseudo-lipoblastic appearance. No true
      lipoblasts were seen and none had the characteristic vasculature of a myxoid
      liposarcoma or the characteristic hyperchromatic cells of well-differentiated
      liposarcoma. The stromal background of all cases contained characteristic wiry
      collagen and myxoid ground substance. The myxoid ground substance was prominent
      in four cases. Immunohistochemical stains for CD34 highlighted the bland spindle
      cells in all cases. The combination of the histologic features and the
      immunoreactivity for CD34 confirmed the diagnosis. Spindle cell lipoma should be
      considered in the differential diagnosis of oral cavity mesenchymal tumors.

PMID- 16456322
TI  - Bacillary angiomatosis associated with pseudoepitheliomatous hyperplasia.
AB  - Bacillary angiomatosis is an opportunistic bacterial infection caused by either
      Bartonella henselae or B. quintana. The classic histologic presentation of
      bacillary angiomatosis involves three components: a lobular proliferation of
      capillaries with enlarged endothelial cells, neutrophilic debris, and clumps of
      finely granular material identified as bacteria with staining techniques.
      Pseudoepitheliomatous hyperplasia is a histologic reaction pattern characterized
      by epithelial proliferation in response to a variety of stimuli, including
      mycobacterial, fungal, and bacterial infections. We describe a case of bacillary
      angiomatosis associated with pseudoepitheliomatous hyperplasia in an
      immunocompromised patient with Acquired Immunodeficiency Syndrome. Histologic
      examination of a finger lesion demonstrated a capillary proliferation with
      neutrophilic debris and characteristic amorphous granular deposits. Warthin
      Starry and Giemsa staining revealed clumps of coccobacilli. Cervical lymph node
      tissue also revealed organisms identified as Bartonella with PCR techniques.
      Stains and cultures for acid fast bacilli, fungus, and bacteria were negative. To
      our knowledge, there has been only one other report of bacillary angiomatosis
      presenting with pseudoepitheliomatous hyperplasia. We conclude that the
      differential diagnosis of entities associated with pseudoepitheliomatous
      hyperplasia should be expanded to include bacillary angiomatosis.

PMID- 16456323
TI  - Langerhans cell sarcoma.
AB  - Proliferations of Langerhans cells can be histologically divided into
      cytologically benign Langerhans cell proliferations, which include the clinical
      syndromes of Langerhans cell histiocytosis, and cytologically malignant
      Langerhans cell sarcoma. We report a Langerhans cell sarcoma in a 33-year-old
      male that arose on the posterior thigh with subsequent regional lymph node
      involvement. Conventional microscopic, immunohistochemical, and ultrastructural
      analysis confirmed Langerhans cell differentiation. Aberrant CD31 expression,
      similar to that described previously in Langerhans cell histiocytosis, was
      prominent in this tumor, possibly enhancing its migratory capabilities.

PMID- 16456325
TI  - Incidental granular parakeratosis associated with molluscum contagiosum.
AB  - A patient presented with a 4-month history of slowly progressive pruritic papules
      on her trunk and extremities. Biopsies from 2 of these lesions revealed molluscum
      contagiosum. One of the biopsies also showed several small foci of granular
      parakeratosis. Based on the clinical features and course of this patient, the
      granular parakeratosis seems to be an incidental finding.

PMID- 16456324
TI  - Lymphoepithelioma-like carcinoma of the skin in a tunisian patient.
AB  - Lymphoepithelioma-like carcinoma of the skin (LELCs) is a rare cutaneous neoplasm
      with histologic features resembling lymphoepitheliomatous tumors of the
      nasopharynx. The association of lymphoepitheliomas with Epstein-Barr Virus (EBV)
      at some extracutaneous sites is well documented. In contrast, the presence of EBV
      in LELCs has never been shown in either Caucasians or Asian patients. We present
      the first case of LELCs in a Tunisian patient, a 78-year-old woman who presented
      with a nodule of the right cheek of 2 months' duration. The patient underwent
      surgical excision and there was no evidence of local recurrence 6 months later.
      Histologically, the entire dermis was occupied by lobules composed of atypical
      epithelial cells surrounded by a dense lymphoplasmacytic infiltrate.
      Immunohistochemical examination showed that the epithelial tumor cells were
      positive for cytokeratin and epithelial membrane antigen. In situ hybridization
      investigations for the presence of EBV-encoded RNA showed negative results. Our
      findings suggest that LELCs is not related to EBV among North African patients.

PMID- 16456326
TI  - Adverse antibiotic-induced eruptions associated with epstein barr virus infection
      and showing Kikuchi-Fujimoto disease-like histology.
AB  - The antibiotic-induced eruption of infectious mononucleosis is a well-known
      clinical phenomenon. Latent viral infection with herpesviridae (eg, human herpes
      virus 6 (HHV-6) and Epstein-Barr virus (EBV)) is suspected to play a role in the
      drug hypersensitivity syndrome. The cutaneous pathologic findings have not been
      reported in the former, and are infrequently reported in the latter entity.
      Herein, we describe the biopsy findings of a cefprozil-induced rash in infectious
      mononucleosis and a minocycline-associated drug hypersensitivity syndrome. Biopsy
      of these exanthematous eruptions revealed an acute vacuolar interface superficial
      and deep perivascular and interstitial lymphocytic dermatitis. CD8(+) lymphocytes
      predominated and were associated with non-neutrophilic nuclear (karyorrhectic)
      debris and numerous small CD68(+) and CD123(+) monocytes. These aforementioned
      features have been described in cutaneous lesions of Kikuchi-Fujimoto disease, an
      entity whose clinicopathologic findings overlap with both infectious
      mononucleosis and lupus erythematosus. Serologic evidence of active and chronic
      active EBV infection was found in both patients, respectively. No evidence of EBV
      or HHV6 was found in the cutaneous lesions. Plasmacytoid monocytes
      (CD68(+)/CD123(+) cells), which produce type I interferon, are believed to play a
      role in viral immunity by protecting other cells from viral infections and
      promoting survival of antigen-activated T cells. Their presence in these two
      putative examples of viral-drug immune dysregulation could be a clue to
      pathogenesis and represent a common cellular component of some adverse cutaneous
      drug eruptions.

PMID- 16456327
TI  - Muir-torre syndrome with intriguing squamous lesions: a case report and review of
      the literature.
AB  - Muir-Torre syndrome (MTS) is an autosomal, dominantly inherited disorder
      characterized by sebaceous neoplasms and visceral malignancies. We report a 56
      year-old woman who underwent resections of extraocular sebaceous carcinoma,
      sebaceous epithelioma, actinic keratosis, and keratoacanthoma (KA)-like squamous
      cell carcinoma (SCC) with venous invasion metachronously over a 9-year period.
      Because of the mixed, unusual features of the skin lesions, and her history of
      endometrial and colorectal cancers that had been resected 12 years and 1 year,
      respectively, before the present event, a possible diagnosis of Muir-Torre
      syndrome was suggested. Immunohistochemical studies revealed loss of hMSH2
      expression in all the cutaneous lesions including the actinic keratosis, and also
      in the endometrial and colorectal cancers. This patient presented with intriguing
      squamous lesions including keratoacanthoma-like squamous cell carcinoma that
      showed venous invasion and actinic keratosis, and associated loss of hMSH2
      expression, in addition to the sebaceous neoplasms typical of Muir-Torre
      syndrome.

PMID- 16456328
TI  - Epidermotropically metastatic pancreatic adenocarcinoma.
AB  - We describe an epidermotropically metastatic pancreatic mucinous ductal
      adenocarcinoma on the scalp. Neoplastic glandular structures that varied in size
      and shape containing abundant mucin within the lumens and in the neoplastic cells
      were present within a seborrheic keratosis and adjacent normal epidermis. Similar
      neoplastic glandular structures were present in the dermis, some within adnexal
      epithelium and lymphatic vessels. The patient's history of pancreatic mucinous
      ductal adenocarcinoma and immunohistochemical staining pattern of carbohydrate
      antigen 19-9 (CA 19-9) confirmed the diagnosis.

PMID- 16456329
TI  - Trichoepithelioma with giant and multinucleated neoplastic epithelial cells.
AB  - We report an unusual example of trichoepithelioma containing giant and
      multinucleated cells in the epithelial compartment. The patient was a 52-year-old
      woman who presented with a solitary nodule on the scalp measuring 2 cm of
      apparently long duration. The biopsy revealed a typical trichoepithelioma. The
      unusual feature was the presence in some epithelial nodules of large epithelial
      cells with hyperchromatic nuclei and no visible nucleoli that exceed 3 to 5 times
      the adjacent follicular germinative cells. Often, multinucleated cells were seen.
      Rare nodules were almost entirely composed of giant/multinucleated cells. The
      majority of the nodules containing giant cells were situated in the deeper
      portion of the neoplasm. No mitoses were seen in these giant cells. No enlarged
      or multinucleated cells were seen in the stroma. The neoplastic epithelial cells
      were diffusely reactive for bcl-2, including the giant and multinucleated cells.
      The proliferating rate was low; Ki-67 stained some giant cells. CD34 stained the
      stroma. We believe that the focal presence of pleomorphic giant cells in
      trichoepithelioma has no clinical or prognostic implications and does not denote
      its "malignant transformation".

PMID- 16456330
TI  - Clinical pathologic challenge. Cellular neurothekeoma.

PMID- 16456331
TI  - The evolution of dermatopathology -- the American experience.

PMID- 16456332
TI  - The spitzoid lesion: the importance of atypical variants and risk assessment.

PMID- 16456333
TI  - Vulvar toker cells: the long-awaited missing link: a proposal for an origin-based
      histogenetic classification of extramammary paget disease.

PMID- 16456335
TI  - What don't we know, and when did we know that we didn't know it?

PMID- 16456339
TI  - The use of gonadotropin-releasing hormone antagonist in ovarian stimulation.

PMID- 16456340
TI  - Evaluation and treatment of the poor responder.

PMID- 16456338
TI  - Patient preparation and standard stimulation regimens using gonadotropin
      releasing hormone agonists.

PMID- 16456341
TI  - The fallopian tube and in vitro fertilization.

PMID- 16456342
TI  - Oocyte donation.

PMID- 16456343
TI  - Male infertility: evaluation and sperm retrieval.

PMID- 16456344
TI  - Micromanipulation in assisted reproductive technology: intracytoplasmic sperm
      injection, assisted hatching, and preimplantation genetic diagnosis.

PMID- 16456345
TI  - Choosing between day 3 and day 5 embryo transfers.

PMID- 16456346
TI  - The uterus and in vitro fertilization.

PMID- 16456347
TI  - Embryo transfer technique.

PMID- 16456348
TI  - Are adverse pregnancy and fetal outcomes more common with assisted reproductive
      technologies? What should patients be told?

PMID- 16456349
TI  - Genetic assessment and development of children that result from assisted
      reproductive technology.

PMID- 16456351
TI  - Clinical pelvimetry.

PMID- 16456350
TI  - Do we need to advocate for vaginal delivery?

PMID- 16456352
TI  - Vaginal birth after cesarean: assessing maternal and perinatal risks-
      contemporary management.

PMID- 16456353
TI  - Vaginal delivery of twins.

PMID- 16456355
TI  - Postpartum hemorrhage: abnormally adherent placenta, uterine inversion, and
      puerperal hematomas.

PMID- 16456354
TI  - Advantages of vaginal delivery.

PMID- 16456356
TI  - Breech delivery before and after the term breech trial.

PMID- 16456359
TI  - A systematic approach to the physiologic adaptations of pregnancy.
AB  - When a woman learns that she is pregnant, her emotions are like a roller coaster.
      To her, she is pregnant. She begins to plan all the things that could be and is
      in constant motion to await the 9 months until the arrival of her bundle of joy.
      However, to those of us in the perinatal nursing field, it means so much more.
      The pregnant woman's body goes through some profound anatomical, physiologic, and
      biochemical changes to adapt to and support the entire pregnancy, which
      ultimately support the growing fetus. Although these physiologic changes are
      normal, often they can be misinterpreted as disease. These changes may also
      unmask or worsen a preexisting condition or disease, ultimately because the
      pregnant woman's body cannot adequately adapt to the changes of pregnancy. It is
      essential to know and understand the physiology-the inner workings-of both the
      mother and the fetus. This includes the basic adaptations related to pregnancy,
      placental physiology and action, uterine activity physiology, and fetal heart
      rate regulation, although this article will focus on maternal and uterine
      physiology only.

PMID- 16456360
TI  - Critical illness during pregnancy: considerations for evaluation and treatment of
      the fetus as the second patient.
AB  - When a critically ill woman is pregnant, clinical interventions for the mother
      can have a profound effect on fetal status. It is essential that the fetus be
      considered as the second patient when developing the plan of care. The most
      practical solution for providing comprehensive care to pregnant women in the
      intensive care unit (ICU) is a collaborative approach involving members of the
      ICU and the perinatal team, each contributing their unique knowledge and skills
      to the care of the mother and her unborn baby. The purpose of this article is to
      describe a collaborative approach to caring for a pregnant woman in the ICU along
      with a brief overview of fetal assessment for ICU care providers so they can
      become familiar with terms and methods used in assessing fetal status and common
      interventions that promote fetal well-being.

PMID- 16456361
TI  - Cardiac disease in pregnancy.
AB  - Cardiac disease complicates approximately 1% to 3% of pregnancies and is
      responsible for 10% to 15% of maternal mortality. The number of women of
      childbearing age with congenital disease is increasing as advances in diagnosis
      and treatment improve survival rates and overall health, allowing successful
      pregnancy. Pregnant women with severe cardiac disease or women who experience a
      cardiac event during pregnancy will require admission and stabilization in an
      adult critical care unit. This group of patients can prove challenging for the
      obstetrical staff and the critical care staff because they require blending of
      the knowledge and skills of 2 highly specialized areas of healthcare. The key
      component to a comprehensive and organized approach to management that ensures
      the best possible outcome for the woman is a multidisciplinary team that devises
      a plan on the basis of the most current information, communicates with each other
      and the patient effectively, and assumes responsibility for implementation of the
      plan. The purpose of this article is to review management of the woman with
      cardiac disease throughout pregnancy.

PMID- 16456362
TI  - Trauma during pregnancy.
AB  - Trauma is the leading nonobstetrical cause of maternal death. The effect of
      trauma on the pregnant woman and unborn fetus can be devastating. The major
      causes of maternal injury are blunt trauma, penetrating trauma, burns, falls, and
      assaults. There are specific changes associated with pregnancy that are important
      for the clinician to consider when providing care to these patients. Initial
      management of traumatic injuries during pregnancy is essential for maternal and
      fetal well-being. This review outlines common causes of maternal trauma, the
      initial assessment of the pregnant trauma patient, and ongoing care for the
      pregnant trauma patient and unborn fetus.

PMID- 16456364
TI  - Promoting fetal stabilization during maternal hemodynamic instability or
      respiratory insufficiency.
AB  - Fetal oxygenation is primarily determined by maternal oxygenation and uterine
      blood flow. Several physiologic adaptations during pregnancy support
      uteroplacental perfusion and, thus, fetal oxygenation. However, the physiologic
      changes required to sustain the metabolic demands of pregnancy may also
      predispose the parturient to decompensation when critical illness is superimposed
      upon pregnancy. In general, the critically ill gravid woman is treated similarly
      to the nonpregnant adult, with the exception of accomodating the physiologic
      changes of pregnancy and evaluating fetal well-being. An overview of the
      physiology of fetal oxygenation, impact of critical care interventions upon the
      fetus, and evaluation of the fetus is provided.

PMID- 16456365
TI  - Psychosocial needs of the critically ill obstetric patient: the nurse's role.
AB  - A critically ill obstetric patient can present a challenging and rewarding
      experience for the nurse who is accustomed to caring for the typical intensive
      care unit patient. This patient population makes up a small percentage of the
      average daily census in adult critical care units across the country. The patient
      population accounts for less than 2% of admissions in the developed countries,
      and these patients experience a very low mortality rate. This article will
      describe those psychosocial needs and address the nurse's role in meeting the
      needs. A case study will be presented to provide specific points for focus.

PMID- 16456366
TI  - The neonatal nurse's role in parental attachment in the NICU.
AB  - Parent/infant attachment or bonding is a naturally occurring event that begins
      during the prenatal period. The feelings of attachment strengthen when fetal
      movement is felt and grow stronger with parent/infant interaction after birth.
      Parents who have a newborn requiring intensive care can have a disruption or
      delay in this attachment process. Neonatal nurses are in a unique position to
      assess this process and intervene to promote attachment behaviors.

PMID- 16456367
TI  - Unmet needs of family members in the medical intensive care waiting room.
AB  - The descriptive, exploratory study consisted of 30 adult family members who
      completed a 2-part instrument: the Demographics Data Questionnaire and the Needs
      Met Inventory. Data were analyzed using descriptive and inferential statistics.
      The top 10 always met/usually met needs and the top 10 never met/sometimes met
      needs were reported in the order of importance during the first 24 to 36 hours
      after admission of a patient to the medical intensive care unit (MICU). The items
      under the subscale of information ranked highest as needs met. Unmet needs were
      to talk about negative feelings such as guilt and anger; to talk about the
      possibility of the patient's death; to have explanations of the environment
      before going into the MICU for the first time; to visit anytime; to talk to the
      same nurse every day; to have explanations given that are understandable; to feel
      there is hope; to have good food available in the hospital; to be assured it is
      alright to leave the hospital for a while; and to feel accepted by the staff.

PMID- 16456368
TI  - Collaborative development of an insulin nomogram for intensive insulin therapy.
AB  - A significant reduction in morbidity and mortality can be achieved by using
      intensive insulin therapy to achieve normoglycemia in the critically ill patient.
      Nurses hourly titrate insulin infusion rates using protocols, most often in chart
      form, to guide practice. Despite the reported development of several intensive
      insulin protocols, information about the accuracy, practicality, ease of
      calculation, and preferences of critical care nurses have not been studied. The
      purpose of this study was to test a newly developed nomogram to determine if it
      was clinically practical, easily understood, and more quickly and accurately used
      than existing protocols in chart form. Three cohorts of nurses (N = 153), with an
      average of 9 years experience in critical care, performed calculations of insulin
      doses on the basis of hypothetical patient data, using chart and nomogram
      protocols. Time, accuracy, preference, and feedback were examined over all 3
      phases. No statistical significance was found between the chart and nomogram
      methods regarding time to complete the calculations nor was there any significant
      effect of experience on the time it took to complete the calculations or the
      accuracy of the resultant answers. Overall, the accuracy of the calculations
      improved with each revision of the nomogram. The nurses did not have a preference
      of one tool over another but gave extensive feedback that helped refine the
      nomogram. The resultant nomogram was shown to be easy to use, helpful in
      improving the accuracy of insulin dosage calculation, and judged to be practical
      by the nurses who would use the tool at the bedside.

PMID- 16456370
TI  - Transplant strategies for patients with myelodysplastic syndromes.
AB  - PURPOSE OF REVIEW: Hematopoietic cell transplantation offers potentially curative
      therapy for patients with myelodysplastic syndrome. The median patient age at
      diagnosis, however, is about 70 years, which has limited the application of
      conventional hematopoietic cell transplantation. In addition, the optimum timing
      of transplantation remains controversial. RECENT FINDINGS: The omission of high
      dose total body irradiation, dose adjustments of busulfan to achieve defined
      target levels, the use of fludarabine instead of cyclophosphamide as an immune
      suppressive agent, the addition of melphalan, and the incorporation of
      antithymocyte globulin appear to have contributed to better tolerability of new
      transplant regimens. Reduced-intensity conditioning regimens are associated with
      a decrease in nonrelapse mortality and allow for successful hematopoietic cell
      transplantation even in patients 60-70 years of age. Among patients with less
      advanced/low-risk myelodysplastic syndrome (< 5% marrow myeloblasts), 3-year
      survivals of 65-75% are achievable with human leucocyte antigen-matched related
      and unrelated donors. Among patients with more advanced/high-risk disease, the
      probability of posttransplant relapse ranges from 10 to 40%, and, as a result,
      relapse-free survival is inferior. In addition to disease stage, comorbid
      conditions, pretransplant chemotherapy, conditioning regimen and source of stem
      cells, affect transplant outcome. SUMMARY: Modifications of transplant
      conditioning regimens have reduced transplant-related mortality, allowing
      successful hematopoietic cell transplantation in increasingly older patients.
      Graft versus host disease, both acute and chronic, and posttransplant relapse
      remain challenging problems.

PMID- 16456371
TI  - The role of HOX genes in myeloid leukemogenesis.
AB  - PURPOSE OF REVIEW: Homeodomain proteins of the Hox family play an important role
      in regulation of normal hematopoiesis. Substantial evidence also indicates that
      abnormal Hox protein expression is functionally significant in the pathogenesis
      of acute myeloid malignancies. The purpose of this review is to outline recent
      progress in understanding molecular mechanisms involved in Hox regulation of
      myelopoiesis and myeloid leukemogenesis. RECENT FINDINGS: Since Hox proteins
      function as transcription factors, recent studies have focused on identifying Hox
      target genes. Various approaches to this problem have been taken, including high
      throughput screening techniques. In these studies, expression profiles of
      hematopoietic cells overexpressing various Hox proteins have been analyzed to
      obtain initial information about potential target genes. Identification of common
      and unique sets of target genes for various Hox proteins will shed light on
      function and regulation of the Hox code in developing hematopoietic cells.
      SUMMARY: Recent studies have generated some intriguing information about
      potential Hox target genes involved in myelopoiesis and leukemogenesis. A number
      of issues regarding Hox protein function are unresolved, however. These issues
      include determining whether the effects of various Hox proteins are redundant
      versus antagonistic, identifying mechanisms which regulate Hox protein function
      and mechanisms by which Hox proteins modulate target gene transcription in a
      context-dependent manner.

PMID- 16456372
TI  - Allogeneic hematopoietic stem cell transplantation for myelofibrosis.
AB  - PURPOSE OF REVIEW: This review summarizes the current status and new developments
      in allogeneic hemopoietic stem cell transplantation strategies for patients with
      myelofibrosis with myeloid metaplasia, focusing on novel concepts of allogeneic
      transplantation with reduced-intensity conditioning. RECENT FINDINGS: No
      substantial progress has been made in the conventional management of
      myelofibrosis with myeloid metaplasia. Allogeneic hemopoietic stem cell
      transplantation represents the only treatment modality with proven curative
      potential. Standard-dose conditioning regimes followed by allogeneic
      transplantation are associated with a relatively high transplant-related
      mortality. Reduced-intensity conditioning regimens have substantially reduced
      treatment-related mortality. This result is from three studies on myelofibrosis
      with myeloid metaplasia including more than 60 patients overall. The optimal
      conditioning regimen for this condition is unknown, in particular the utility of
      using T-cell depleted stem cells to reduce graft versus host disease is not
      documented. Emerging concepts include new risk classification for a better
      provision of the transplant outcome, and splenectomy before transplantation for
      reducing tumor burden. SUMMARY: The data on hemopoietic stem cell transplantation
      with reduced-intensity conditioning in myelofibrosis with myeloid metaplasia are
      encouraging. An accurate risk stratification is a pivotal procedure for selecting
      patients who will receive the greatest benefit for transplantation. Reduced
      intensity conditioning should be further evaluated within clinical trials, in
      particular for assessing the role of splenectomy and for testing the optimal
      conditioning regimen.

PMID- 16456373
TI  - Overcoming drug resistance in chronic myeloid leukemia.
AB  - PURPOSE OF REVIEW: Despite the excellent clinical results with imatinib in
      chronic myeloid leukemia, most patients have minimal residual disease and others
      will develop resistance and may eventually progress. Thus there is a need for
      developing approaches to overcome and prevent resistance to imatinib. RECENT
      FINDINGS: Several new agents have been developed with significant activity in
      imatinib-resistant chronic myeloid leukemia. A second generation of more potent
      tyrosine kinase inhibitors, some with dual activity against Abl and Src, have
      shown very impressive results. Other agents, such as hypomethylating agents,
      farnesyl transferase inhibitors and homoharringtonine, have also shown
      preclinical and clinical promise. The use of vaccines as a way of providing an
      immunomodulatory approach to chronic myeloid leukemia is starting to develop as a
      major strategy to achieve eradication of the disease. SUMMARY: Multiple effective
      agents are being developed to overcome resistance to imatinib. The challenge for
      the future is to incorporate them into effective strategies that can eliminate
      the disease and cure all patients with chronic myeloid leukemia.

PMID- 16456374
TI  - New insights into the pathogenesis and drug treatment of myelofibrosis.
AB  - PURPOSE OF REVIEW: Myelofibrosis with myeloid metaplasia was first described in
      1879, classified as a myeloproliferative disorder in 1951, and characterized as a
      clonal stem cell disorder in 1978. Despite the passing of time, the molecular
      basis of the disease has remained elusive although substantial progress has been
      made regarding the pathogenesis of the associated bone marrow stromal reaction.
      Advances have also been meager in terms of treatment for disease complications,
      including anemia, splenomegaly, and leukemic transformation. RECENT FINDINGS: At
      the molecular level, a JAK2 tyrosine kinase mutation (JAK2) has recently been
      described in a spectrum of myeloproliferative disorders including myelofibrosis
      with myeloid metaplasia with the reported mutational frequency ranging from 35%
      to 57% with 9-29% homozygosity. To date, the presence of JAK2 in myelofibrosis
      with myeloid metaplasia has not been shown to have prognostic relevance. Other
      recent observations of potential pathogenetic relevance in this disease include
      the description of a highly specific chromosomal translocation
      {der(6)t(1;6)(q23;p21)}, the demonstration of an epigenetic downregulation of the
      retinoic acid receptor-beta2 expression in CD34 cells, and the direct implication
      of transforming growth factor-beta1 in thrombopoietin-driven experimental
      myelofibrosis in mice. From a therapeutic standpoint, benefit to a subset of
      patients has been demonstrated for both allogeneic stem cell transplantation and
      novel drugs, including thalidomide and lenalidomide. SUMMARY: Recent advances in
      the pathogenesis of myelofibrosis with myeloid metaplasia are expected to
      facilitate the development of molecularly targeted therapy. In the mean time,
      current management strategies include observation, participation in experimental
      drug therapy, and allogeneic stem cell transplantation for low-risk, intermediate
      risk, and high-risk disease, respectively.

PMID- 16456375
TI  - Essential thrombocythemia: scientific advances and current practice.
AB  - PURPOSE OF REVIEW: Median survival in essential thrombocythemia exceeds 20 years
      and clinical course is usually indolent with a minority of patients experiencing
      thrombohemorrhagic complications. Leukemic, polycythemic, or fibrotic disease
      transformation in essential thrombocythemia is an infrequent occurrence with a 15
      year cumulative risk of approximately 5% or less in each instance. The major
      incentives for this review have been the recent description of an activating JAK2
      tyrosine kinase mutation (JAK2 (V617F)) in essential thrombocythemia, related
      myeloproliferative disorders, and the impact on clinical practice from the
      publication of a major treatment trial. RECENT FINDINGS: Several studies have
      reported on the occurrence of JAK2(V617F) in approximately 50% of patients with
      essential thrombocythemia and its presence has been associated with advanced age
      at diagnosis, higher hemoglobin and leukocyte levels, and increased rate of
      polycythemic transformation. In contrast, the mutation did not appear to affect
      the incidence of thrombotic, leukemic, or fibrotic events. There is increasing
      evidence regarding the thrombogenic role of neutrophils in essential
      thrombocythemia and this might partly explain the superior overall performance by
      hydroxyurea, compared with anagrelide, in a recent randomized study. SUMMARY:
      Although it is in vogue to consider essential thrombocythemia as more than one
      disease in terms of both molecular phenotype (presence or absence of JAK2(V617F))
      and putative pattern of myelopoiesis (monoclonal versus polyclonal), it is yet to
      be shown that such differences influence either the natural history of the
      disease or current therapy. From a treatment standpoint, hydroxyurea is now
      confirmed to be the drug of choice for high-risk patients with essential
      thrombocythemia.

PMID- 16456376
TI  - Bibliography. Current world literature. Myeloid disease.

PMID- 16456378
TI  - Unfulfilled palliative care needs of chronic obstructive pulmonary disease
      patients.

PMID- 16456379
TI  - Chronic obstructive pulmonary disease: effects beyond the lungs.
AB  - PURPOSE OF REVIEW: This article reviews the systemic effects of chronic
      obstructive pulmonary disease in general and the musculoskeletal effects and
      cachexia in particular. RECENT FINDINGS: Shift in muscle fiber type from I to II,
      reduction of capillary/mitochondria ratio, reduction of oxidative enzymes and
      oxidative capacity, alteration in amino acid profile, changes in respiratory
      muscle dynamics, activation of the ubiquitin-proteosome pathway with loss of
      contractile proteins are some of the factors found to cause muscle dysfunction in
      chronic obstructive pulmonary disease. Chemotaxis and capability to produce more
      reactive oxygen species and to cause extracellular proteolysis are enhanced in
      neutrophils of chronic obstructive pulmonary disease patients. Tumor necrosis
      factor-alpha is shown to cause loss of myosin chains in a time and dose-dependent
      fashion and to induce production of reactive oxygen species through activation of
      the cyclooxygenase pathway. Inflammation and oxidative stress caused by reactive
      oxygen species fuel each other. Weight loss due to muscle wasting (cachexia) in
      chronic obstructive pulmonary disease is not solely related to malnutrition and
      is an independent predictor of mortality. Causative factors for cachexia include
      cytokine effects, protein degradation enhanced by increased ubiquination,
      upregulation of mRNA for key enzymes, increased energy expenditure and
      neurohormonal effects such as leptin production and an imbalance in anabolic and
      catabolic hormone homeostasis. SUMMARY: The findings noted above may well have
      the common link of inflammation in and beyond the lungs.

PMID- 16456380
TI  - Prevalence and impact of depression in chronic obstructive pulmonary disease
      patients.
AB  - PURPOSE OF REVIEW: This review presents recent advances in the study of the
      depression that is so often co-morbid with chronic obstructive pulmonary disease.
      The discussion includes prevalence, etiology, impact and management. RECENT
      FINDINGS: Efforts continue to find a reliable prevalence rate for co-morbid
      depression in patients with chronic obstructive pulmonary disease but studies
      regularly find depression in 20-60% of these patients. Multiple etiologies
      contribute to this elevated rate including genetic predisposition, grief
      reaction, and effects of chronic obstructive pulmonary disease on the central
      nervous system. Once depression develops patients are less adherent to treatment
      plans, lose function and, potentially, suffer worse outcomes in exacerbations.
      Management of depression in chronic obstructive pulmonary disease continues to be
      primarily empirical. There are few quality studies demonstrating the usefulness
      of antidepressants in this population. Some studies suggest selective serotonin
      reuptake inhibitors will be effective, but require replication in larger groups.
      Other interventions including psychotherapy, physical rehabilitation, and
      improved social support are accumulating supporting data, but further research is
      needed. SUMMARY: Depression is present in up to 60% of patients with chronic
      obstructive pulmonary disease. It jeopardizes patients' ability to utilize
      treatment and may increase their risk for poor outcomes. Effective management
      will require high-quality studies and a multidisciplinary approach.

PMID- 16456381
TI  - Role of nontypeable Haemophilus influenzae in exacerbations and progression of
      chronic obstructive pulmonary disease.
AB  - PURPOSE OF REVIEW: Nontypeable Haemophilus influenzae is the most common
      bacterial pathogen associated with airway infection in chronic obstructive
      pulmonary disease, both in stable disease and during exacerbations. Past attempts
      to elucidate its role as a pathogen in this disease yielded confusing and
      contradictory results, leading to its designation as an 'innocent bystander' with
      little if any pathogenic role in exacerbations and stable disease. Application of
      modern understanding of bacterial pathogenesis and of innovative research
      methodologies, however, has considerably clarified its role. RECENT FINDINGS:
      Acquisition of antigenically diverse strains of nontypeable H. influenzae which
      engender a neutrophilic inflammatory response and strain-specific immunity
      appears to be the mechanism underlying recurrent exacerbations of chronic
      obstructive pulmonary disease. In the stable phase of the disease, this pathogen
      appears to be an inflammatory stimulus in the lower airways with the potential to
      contribute to progressive airway obstruction that is characteristic of the
      condition. Several mechanisms may allow the infection to persist in the lower
      airways of patients with chronic obstructive pulmonary disease, including tissue
      invasion, antigenic alteration and biofilm formation. SUMMARY: Though much has
      been learnt about nontypeable H. influenzae in chronic obstructive pulmonary
      disease, new therapeutic and preventive approaches require an even greater
      understanding of this host-pathogen interaction.

PMID- 16456382
TI  - Alpha-1-antitrypsin replacement therapy: current status.
AB  - PURPOSE OF REVIEW: Alpha-1-antitrypsin deficiency is a relatively common genetic
      disease that predisposes to the development of early-onset emphysema and, in some
      instances, liver disease. The use of alpha-1-antitrypsin replacement therapy in
      the treatment of alpha-1-antitrypsin deficiency related emphysema is much debated
      and the purpose of this review is to examine the results of recent studies. We
      will comment briefly on the pathogenesis and epidemiology of the disease together
      with new therapeutic approaches currently under intense research. RECENT
      FINDINGS: Several nonrandomized observational studies and one meta-analysis on
      the clinical effectiveness of alpha-1-antitrypsin replacement treatment showed a
      favourable result towards reducing forced expiratory volume in 1 s (FEV1)
      deterioration in alpha-1-antitrypsin-deficient individuals with moderate lung
      disease or accelerated FEV1 decline. Improved ways of monitoring disease
      progression, including computed tomography scanning and exacerbations, are being
      proposed as primary endpoints. Apart from one small randomized, placebo
      controlled trial using computed tomography scanning, which showed a trend toward
      preservation of lung density on scanning with treatment, the literature lacks
      proof of effectiveness from large randomized trials. SUMMARY: There might be a
      possible, but so far unproven, role of alpha-1-antitrypsin augmentation therapy
      in reducing the progression of emphysema in subsets of patients with alpha-1
      antitrypsin deficiency. Placebo-controlled, randomized clinical trials are
      required to draw firm conclusions. Recent advances in the understanding of the
      molecular pathology provide opportunities for development of new therapeutic
      targets for this genetic disorder.

PMID- 16456383
TI  - Use of theophylline in chronic obstructive pulmonary disease: examining the
      evidence.
AB  - PURPOSE OF REVIEW: The role of theophylline in the management of chronic
      obstructive pulmonary disease remains controversial. This review was undertaken
      to determine the efficacy of theophylline in patients with stable disease. RECENT
      FINDINGS: Twenty-two good quality randomized controlled trials were included in
      this systematic review. The review showed that theophylline significantly
      improved forced expiratory volume in 1 s and forced vital capacity (weighted mean
      difference 0.10 L; 95% confidence interval 0.04-0.16 and weighted mean difference
      0.21 L; 95% confidence interval 0.10-0.31, respectively). V also improved with
      theophylline (weighted mean difference 195.27 mL/min; 95% confidence interval
      112.71-277.83), as did Pa and Pa (weighted mean difference 1.45 mmHg; 95%
      confidence interval 0.26-2.65 and weighted mean difference -1.09 mmHg; 95%
      confidence interval -1.83 to -0.35, respectively). Patients preferred
      theophylline over placebo (relative risk 2.27; 95% confidence interval 1.26
      4.11). Theophylline increased the risk of nausea, however, compared with placebo
      (relative risk 7.67; 95% confidence interval 1.47-39.94). SUMMARY: This review
      has shown that oral theophylline plays an important role in the management of
      patients with stable chronic obstructive pulmonary disease by improving lung
      function, arterial blood gas tensions and ventilatory capacity. Patients also
      preferred treatment with theophylline when compared with placebo. The benefits of
      theophylline in stable chronic obstructive pulmonary disease, however, have to be
      weighed against the risk of adverse effects, particularly nausea.

PMID- 16456384
TI  - Oxygen supplementation for chronic obstructive pulmonary disease patients during
      air travel.
AB  - PURPOSE OF REVIEW: By 2008 it is projected that over two billion people will be
      travelling by commercial aircraft each year. With an ageing population and
      treatment improvements, many of these travellers will have lung disease,
      particularly chronic obstructive pulmonary disease. Current guidelines as to
      whether a patient requires supplemental oxygen during the flight are based on
      limited research evidence. Awareness of the increased risk has resulted in recent
      scientific interest in this area. RECENT FINDINGS: Studies have demonstrated a
      lack of consistency in international guideline recommendations when performing
      assessments within the respiratory laboratory. This has led to more specific
      analysis of patients, including in-flight assessments, the inclusion of exercise
      stress and more interest in actual cabin pressure conditions. SUMMARY: Commercial
      air travel is generally safe for patients with chronic obstructive pulmonary
      disease when their disease is stable. All current guidelines reflect the
      considerable uncertainty in relation to the clinical circumstances when oxygen
      prescription during flight is essential. Currently planned flight outcome studies
      will provide more precise risk quantification.

PMID- 16456385
TI  - Classification and approach to bronchiolar diseases.
AB  - PURPOSE OF REVIEW: Bronchiolar abnormalities are relatively common and occur in a
      variety of clinical contexts. There have been an increasing number of terms, some
      of which are redundant, used in referring to various forms of bronchiolar
      disorders. The purpose of this review is to provide an updated classification
      scheme to facilitate the clinical approach to patients with suspected bronchiolar
      disease. RECENT FINDINGS: The spectrum of bronchiolar disorders is broader and
      more heterogeneous than previously recognized. In deciphering the potential
      significance of bronchiolar abnormalities, it is useful to distinguish those
      disorders in which the bronchiolar involvement is the dominant pathologic
      process, that is, primary bronchiolar disorders, from parenchymal or large airway
      diseases in which the bronchioles may become secondarily involved. Primary
      bronchiolar disorders include respiratory bronchiolitis, acute bronchiolitis,
      constrictive bronchiolitis, follicular bronchiolitis, diffuse panbronchiolitis,
      mineral dust airway disease, and a few other variants. Interstitial lung diseases
      with a prominent bronchiolar involvement include smoking-related interstitial
      lung diseases, cryptogenic organizing pneumonia, and hypersensitivity
      pneumonitis. Bronchiolitis can also be seen in large airway diseases such as
      chronic bronchitis, bronchiectasis, and asthma. SUMMARY: In the clinical approach
      to a patient with bronchiolar disease, primary bronchiolar disorders should be
      distinguished from predominantly parenchymal or large airway processes with
      bronchiolar involvement. The number of patterns of bronchiolar response to injury
      is limited and these patterns are generally non-specific in regard to cause.
      Appropriate diagnosis and management of patients with bronchiolar disorders
      depend on judicious correlation of clinical, physiologic, and morphologic
      manifestations.

PMID- 16456386
TI  - Bibliography. Current world literature. Obstructive, occupational, and
      environmental diseases.

PMID- 16456387
TI  - Rehabilitation medicine summit: building research capacity.
AB  - The general objective of the "Rehabilitation Medicine Summit: Building Research
      Capacity" was to advance and promote research in medical rehabilitation by making
      recommendations to expand research capacity. The 5 elements of research capacity
      that guided the discussions were (1) researchers; (2) research culture,
      environment, and infrastructure; (3) funding; (4) partnerships; and (5) metrics.
      The 100 participants included representatives of professional organizations,
      consumer groups, academic departments, researchers, governmental funding
      agencies, and the private sector. The small group discussions and plenary
      sessions generated an array of problems, possible solutions, and recommended
      actions. A post-Summit, multiorganizational initiative is called to pursue the
      agendas outlined in this article.

PMID- 16456388
TI  - Factors that lead to successful community integration following severe traumatic
      brain injury.
AB  - OBJECTIVE: To assess and identify predictive factors of community integration of
      people 3 to 15 years after severe traumatic brain injury (TBI). PARTICIPANTS:
      Forty participants with severe TBI (an average of 8.8 years postinjury). MAIN
      OUTCOME MEASURES: The Community Integration Questionnaire, the Community
      Integration Measure, and the Sydney Psychosocial Reintegration Scale. Data
      related to factors that may predict community integration were also collected.
      RESULTS: There was considerable variation in the level of community integration.
      Discriminant function analyses identified the following factors as predictive of
      the level of community integration: severity of injury, age at the time of
      injury, level of disability, and challenging behavior. CONCLUSION: Interventions
      that minimize challenging behavior and disability may make a significant
      difference to the level of community integration experienced by people with
      severe TBI.

PMID- 16456389
TI  - Causes of death following 1 year postinjury among individuals with traumatic
      brain injury.
AB  - OBJECTIVE: To investigate causes of death in individuals with traumatic brain
      injury (TBI). DESIGN: Retrospective cohort study. SETTING: Utilized data from the
      TBI Model Systems National Database, the Social Security Death Index, death
      certificates, and the US population age-race-gender-cause-specific mortality
      rates for 1994. PATIENTS: Two thousand one hundred forty individuals with TBI
      completing inpatient rehabilitation in 1 of 15 National Institute on Disability
      and Rehabilitation Research-funded TBI Model Systems of Care between 1988 and
      2001, and surviving past 1 year postinjury. MAIN OUTCOME MEASURES: Primary cause
      of death based on the International Classification of Diseases--9th Revision-
      Clinical Modification-coded death certificates. RESULTS: Individuals with TBI
      were about 37 times more likely to die of seizures, 12 times more likely to die
      of septicemia, 4 times more likely to die of pneumonia, and about 3 times more
      likely to die of other respiratory conditions (excluding pneumonia), digestive
      conditions, and all external causes of injury/poisoning than were individuals in
      the general population of similar age, gender, and race. CONCLUSION: Long-term
      follow-up of individuals with TBI should increase vigilance for, and prevention
      of, diagnoses frequently causing death (circulatory disorders) and diagnoses with
      a high relative risk of causing death in this population (seizures, septicemia,
      respiratory and digestive conditions, and external causes of injury).

PMID- 16456390
TI  - Barriers to driving and community integration after traumatic brain injury.
AB  - OBJECTIVE: To examine the relations among driving status, perceptions of barriers
      to the resumption of driving, and community integration outcomes after traumatic
      brain injury (TBI). DESIGN: Correlational research using logistic and multiple
      regression analyses, analyses of variance, and covariance. PARTICIPANTS: Fifty
      one survivors of TBI, 6 months to 10 years postinjury. MAIN OUTCOME MEASURES:
      Driving status postinjury, Community Integration Measure, and Craig Hospital
      Assessment and Reporting Technique. RESULTS: Perceptions of barriers to driving
      provided unique information in predicting subjective and objective indices of
      community integration, even after accounting for other potentially pertinent
      variables (eg, injury severity, social support, negative affectivity, and use of
      alternative transportation). Moreover, survivors who had not resumed driving
      showed poorer community integration than did those who had resumed driving.
      Social barriers such as directives against driving from significant others
      accounted for the most variance in survivor driving status. Decisions to cease
      driving were more common among those with no formal driving evaluation than among
      survivors who had been evaluated. CONCLUSIONS: Significant others have
      substantial influence on post-TBI driving outcome. The findings highlight the
      importance of independent driving to community integration, as well as
      psychoeducation of survivors and their families.

PMID- 16456391
TI  - Aggressive behavior following traumatic brain injury: how common is common?
AB  - OBJECTIVE: To assess the prevalence and predictors of aggressive behavior among
      traumatic brain injury (TBI) survivors at 6, 24, and 60 months postdischarge.
      DESIGN: Mixed cross-sectional and longitudinal data from a 5-year follow-up study
      of discharged TBI patients analyzed retrospectively. SETTING: A specialized Brain
      Injury Rehabilitation Service of a tertiary referral hospital. PATIENTS: Two
      hundred twenty-eight (228) patients with moderate to severe TBI. MAIN OUTCOME
      MEASURES: The Overt Aggression Scale; injury-related variables (in particular,
      Glasgow Coma and Outcome scales and posttraumatic amnesia duration); and a
      battery of postdischarge questionnaires (Beck Depression Inventory, Trauma
      Complaints List, General Health Questionnaire, etc). RESULTS: At any given follow
      up period, 25% of the participants were classified as aggressive. Aggression,
      where present, was consistently associated with depression, concurrent traumatic
      complaints, younger age at injury, and low satisfaction with life rather than
      with injury, demographic, or premorbid characteristics. Depression was the factor
      that was most significantly associated with aggressive behavior at all times
      postinjury, followed by a younger age at the time of injury. CONCLUSIONS:
      Aggression is a common, fluctuating, and long-term problem following TBI. The
      underlying association between aggression and psychosocial variables lends
      support to the provision of ongoing outreach services and psychological and
      behavioral interventions for all affected TBI survivors.

PMID- 16456392
TI  - Putting the pieces together: preliminary efficacy of a family problem-solving
      intervention for children with traumatic brain injury.
AB  - OBJECTIVE: To describe a family-centered problem-solving intervention (FPS) for
      pediatric traumatic brain injury (TBI), and to assess the efficacy of the
      intervention in a randomized clinical trial. PARTICIPANTS: Families of 32 school
      aged children with moderate to severe TBI randomly assigned to FPS or usual care
      (UC) group. MAIN OUTCOME MEASURES: Child Behavior Checklist, Brief Symptom
      Inventory, Conflict Behavior Questionnaire. INTERVENTION: Seven-session problem
      solving/skill-building intervention delivered over a 6-month period for the
      participating families. RESULTS: Parents in the FPS group reported significantly
      greater improvements in their children in internalizing symptoms,
      anxiety/depression, and withdrawal than did parents in the UC comparison group.
      CONCLUSIONS: FPS holds promise for reducing child behavior problems, the most
      common and persistent sequelae of TBI.

PMID- 16456393
TI  - Executive memory dysfunctions following mild traumatic brain injury.
AB  - OBJECTIVES: To explore the contribution of executive dysfunctions to mnemonic
      problems in adults with mild traumatic brain injury (MTBI). DESIGN: Prospective
      quasiexperimental between-groups design. PARTICIPANTS: Ninety-nine persons with
      MTBI were compared to 90 control group participants matched for gender, age, and
      education. SETTING: Two Canadian brain injury rehabilitation programs. MAIN
      OUTCOME MEASURE: California Verbal Learning Test. RESULTS: Participants with MTBI
      showed a significant deficit in free recall on the California Verbal Learning
      Test but performed similarly to the comparison group on the recognition task.
      Furthermore, the participants with MTBI were less likely to use semantic
      clustering as a memorizing strategy and made more intrusion errors and false
      positive errors on the recognition task. CONCLUSIONS: While the scores for the
      participants with MTBI are only slightly lower than the norm, they demonstrate
      that MTBI has a negative effect on mnemonic performance. The results are
      explained in terms of a deficit in registration/retrieval processes rather than a
      malfunction of the storage processes. This supports the initial hypothesis that
      executive dysfunctions are detrimental to the quality of mnemonic functions in
      patients with MTBI.

PMID- 16456394
TI  - The impact of community rehabilitation for acquired brain injury on carer burden:
      an exploratory study.
AB  - OBJECTIVES: This study evaluated the relative efficacy of a community
      rehabilitation service and a more traditional outpatient service for carers of
      people with an acquired brain injury. METHODS: Seventeen carers who had received
      a community intervention were retrospectively compared with 24 carers who had
      received an outpatient service. Dependent variables were level of met family
      need, a measure of family dysfunction, carer psychopathology, and carer emotional
      acceptance. RESULTS: The community sample fared significantly better on all
      measures except carer psychopathology. CONCLUSIONS: These results suggest that
      community-based services have efficacy for the carer and family. There is a clear
      need for large clinical trials using standardized instruments to establish what
      models of service delivery benefit carers.

PMID- 16456395
TI  - Brain injury: benzodiazepines, antipsychotics, and functional recovery.

PMID- 16456396
TI  - Atomoxetine for individuals with traumatic brain injury.

PMID- 16456401
TI  - Clinical Research Network launches TONIC trial for treatment of nonalcoholic
      fatty liver disease in children.

PMID- 16456404
TI  - Sodium butyrate-mediated Sp3 acetylation represses human insulin-like growth
      factor binding protein-3 expression in intestinal epithelial cells.
AB  - OBJECTIVES: Butyrate concentrations in the gastrointestinal tract vary greatly
      with age. In intestinal epithelial cells, butyrate enhances gene transcription by
      increasing histone acetylation, rendering the nucleosome open to transcription
      factors. However, it inhibits human insulin-like growth factor binding protein
      (hIGFBP)-3 expression. We therefore hypothesized that butyrate also acts by
      regulating transcription factor acetylation. METHODS: Gene regulation was
      examined in Caco-2 cells. RNA stability was measured after interruption of
      transcription. The activity of deletion mutations of the hIGFBP-3 promoter was
      examined in reporter assays. Transcription factor binding to promoter DNA was
      analyzed. RESULTS: Butyrate did not increase the transcription of a repressor
      because it inhibited hIGFBP-3 mRNA in the absence of protein synthesis. Nor did
      butyrate decrease the stability of hIGFBP-3 mRNA. Analysis of the hIGFBP-3
      promoter demonstrated a butyrate-response element that included the binding sites
      for p300 and Sp1/Sp3. Transfection of Caco-2 cells with E1A, an inhibitor of p300
      acetyltransferase activity, reversed the butyrate-induced repression of hIGFBP-3.
      Because Sp3 represses the initiation of transcription, we studied whether
      butyrate induced Sp3 acetylation. Electrophoretic mobility shift assays of nuclei
      extracted from Caco-2 cells treated with 5 mmol/L butyrate demonstrated an extra,
      heavier band in addition to the Sp3-DNA binding in untreated cells. This
      corresponded to a protein, detected only in butyrate treated cells, that was
      identified both by an anti-Sp3 antibody and by an anti-acetyl lysine antibody.
      CONCLUSIONS: This study demonstrates that butyrate increases the acetylation of a
      nonhistone protein, Sp3, catalyzed by p300 acetyltransferase activity.

PMID- 16456405
TI  - Chemokine production by buccal epithelium as a distinctive feature of pediatric
      Crohn disease.
AB  - OBJECTIVES: Inflammatory bowel diseases (IBD) represent an aberrant immune
      response by the mucosal immune system to luminal bacteria. Because the oral
      mucosa harbors the first epithelial cells that interact with microorganisms, we
      assessed the immunologic activity of buccal epithelium in children with IBD and
      adults with Crohn disease. METHODS: Buccal epithelial cells were obtained from 17
      children and 14 adults with Crohn disease, 18 children with ulcerative colitis,
      and 40 controls. Cells were cultured with and without microbial stimulation.
      Chemokine levels were determined in culture supernatants by cytometric bead array
      and enzyme-linked immunoabsorbent assay. CXCL-8 production was studied by
      immunohistochemical analysis of these cells. CXCL-8 production by
      lipopolysaccharide stimulated monocyte-derived dendritic cells from these
      patients was determined. RESULTS: Compared with controls, pediatric ulcerative
      colitis patients, and adult Crohn disease patients, only in children with Crohn
      disease did buccal epithelial cells exhibit enhanced production of CXCL-8, CXCL
      9, and CXCL-10. In vitro stimulation with lipopolysaccharide or zymosan resulted
      in a further increase of chemokine levels only in cells from pediatric Crohn
      disease patients. CXCL-8 production by stimulated monocyte-derived dendritic
      cells from children with Crohn disease was equal to that of children with
      ulcerative colitis. CONCLUSIONS: Buccal epithelium of children with Crohn disease
      is immunologically active, even in the absence of oral lesions. The enhanced
      chemokine production is associated with pediatric Crohn disease and appears
      restricted to cells derived from the epithelial barrier. Assessment of chemokine
      production by buccal epithelial cells may become a new, rapid, noninvasive test
      for screening and classification of IBD in children.

PMID- 16456407
TI  - Prevalence of celiac disease in Brazilian children with type 1 diabetes mellitus.
AB  - OBJECTIVE: Although the relationship between celiac disease and diabetes mellitus
      type 1 is well recognized, there are no studies of this association in Brazil.
      This study aims to identify the prevalence of celiac disease in a group of
      children with diabetes mellitus type 1 undergoing treatment in the pediatric
      endocrinology division of a university hospital in Minas Gerais, Brazil. METHODS:
      Immunoglobulin (Ig)A and IgG antigliadin antibodies (enzyme-linked
      immunoadsorbent assay) were measured in blood collected from 236 children and
      adolescents with diabetes mellitus type 1. Patients with antigliadin antibodies
      then had jejunal biopsy and determination of antiendomysial antibodies by
      indirect immunofluorescence. RESULTS: Twenty-one patients had IgA or IgG
      antigliadin antibodies. Nineteen underwent jejunal biopsy. Six had mucosal
      alterations compatible with celiac disease; four had nonspecific histologic
      changes; nine had normal biopsies. Thirteen antigliadin antibody-positive
      patients were antiendomysial antibody-negative; one antiendomysial antibody
      negative patient had celiac disease. The prevalence of celiac disease was 2.6%
      among 234 patients. CONCLUSIONS: Measurement of antigliadin antibodies in
      patients with diabetes mellitus type 1 helped in the selection of patients to
      undergo jejunal biopsy. Antiendomysial antibodies were highly specific and
      moderately sensitive in predicting celiac disease. The prevalence of celiac
      disease was higher in diabetics than in the general population, suggesting the
      need for regular screening assessment of diabetic children.

PMID- 16456406
TI  - Serologic and genetic markers of celiac disease: a sequential study in the
      screening of first degree relatives.
AB  - OBJECTIVES: The prevalence of celiac disease (CD) among the relatives and the
      complications of an undiagnosed CD prompted us to identify a useful disease
      screening strategy. METHODS: We studied 441 first degree relatives of 208 CD
      patients by immunoglobulin (Ig)A antiendomysium antibodies (EMA) and
      radioimmunoprecipitation assay (RIA) IgA antitransglutaminase autoantibodies
      (TGAA). Of these, 364 were typed for human leukocyte antigen-DRB1, -DQA1, and 
      DQB1 genes by the polymerase chain reaction sequence specific primers method. It
      was suggested to the autoantibody-positive subjects that they should undergo
      intestinal biopsy. RESULTS: TGAA were positive in 46 of 439 relatives, EMA in 38;
      intestinal lesions related to CD were present in 40 subjects. We also found two
      immunodeficient fathers with duodenal villous atrophy. In three serology-positive
      subjects, permission for intestinal biopsy was refused; for another three
      serology-positive cases, duodenal mucosa was normal. Thus, the strict CD
      prevalence resulted 9.5%, the enlarged prevalence 10.9%. The DQ2/DQ8 heterodimers
      were carried in 231 of 364 subjects and in 38 of 40 biopsy-proven celiac
      patients. Three DQ2-positive parents became positive to the serology during a
      long-lasting follow-up. CONCLUSIONS: On the basis of a carefully conducted study,
      CD prevalence in our series was seen as very high. These data suggest an accurate
      algorithm to select candidates for intestinal biopsy among CD high-risk subjects.
      First, an evaluation of the sensitive RIA TGAA and of total IgA (in IgA
      deficiency RIA IgG anti-tissue transglutaminase assay) should be performed. Then,
      an evaluation of the TGAA and the genetic study would be advisable 2 to 3 years
      later in negative subjects. Those carrying the DQ2/DQ8 heterodimers should
      continue the serologic follow-up; the others need a clinical follow-up.

PMID- 16456408
TI  - Nocturnal acid breakthrough in children with reflux esophagitis taking proton
      pump inhibitors.
AB  - OBJECTIVES: We aimed to determine if nocturnal acid breakthrough occurs in
      children receiving proton pump inhibitors for reflux esophagitis, and to compare
      the healing of esophagitis in children with nocturnal acid breakthrough receiving
      proton pump inhibitors +/- ranitidine. METHODS: This is a prospective, double
      blind study. Endoscopic and histologic esophagitis were scored 0-4 and 0-3,
      respectively. Patients were treated with a proton pump inhibitor twice daily and
      esophagogastric pH monitoring was performed at week 3. Patients with nocturnal
      acid breakthrough were randomized. One group received ranitidine and the other
      received placebo at bedtime in addition to proton pump inhibitor therapy.
      Endoscopy was performed on all patients (with pH monitoring on patients with
      nocturnal acid breakthrough) during the 17th week of therapy. RESULTS: We
      enrolled 18 patients, ages 1 to 13 years (mean = 10.3 years). Mean baseline
      endoscopic and histologic scores were 3.1 +/- 1.4 and 1.8 +/- 0.7, respectively.
      Mean dose of proton pump inhibitor was 1.3 mg/kg +/- 0.6. Nocturnal acid
      breakthrough was documented in 16/18 (89%) patients. Seven patients received
      ranitidine and 9 received placebo. The reflux index improved: mean of 14.3 at
      baseline, 2.0 at week 3 (P = 0.0001), and 5.1 at week 17 (P = 0.09). Nocturnal
      acid breakthrough persisted in 9/12 (75%) patients, 3 of whom received ranitidine
      at bedtime. Esophagitis improved in all patients following therapy: mean
      endoscopy and histology scores were 1.6 +/- 1.8 (P = 0.0020) and 0.8 +/- 0.9 (P =
      0.0013), respectively. Symptoms significantly improved from a mean score of 2.0
      at baseline to 0.4 at week 17 (P = 0.0001). CONCLUSIONS: Nocturnal acid
      breakthrough is common in pediatric patients treated with proton pump inhibitors.
      Reflux index remains normal in spite of nocturnal acid breakthrough. Symptoms and
      esophagitis continued to improve during therapy in spite of nocturnal acid
      breakthrough. There appears to be no additional benefit to supplementation with
      ranitidine at bedtime.

PMID- 16456409
TI  - Effect of maternal consumption of lactobacillus GG on transfer and establishment
      of fecal bifidobacterial microbiota in neonates.
AB  - BACKGROUND: Establishment of the gut microbiota at birth provides a substantial
      source of microbial stimuli for the maturation of the immune system. Deviations
      in this process precede the development of specific diseases providing the
      rationale for the use of probiotics to counteract them. OBJECTIVE: This study was
      designed to characterize both the mother-infant bifidobacteria transfer at birth
      and the development of bifidobacteria microbiota during the first weeks of life
      in infants whose mothers received Lactobacillus rhamnosus GG or placebo. METHODS:
      Species-specific PCR was used to assess the fecal bifidobacterial composition of
      mothers before and after delivery and in infants at 5 days and 3 weeks of age.
      RESULTS: Bifidobacterium longum was the species most commonly found in the
      mothers. Bifidobacterium catenulatum was the most prevalent group in infants at 5
      days of age and B. longum the predominant species at 3 weeks. At 5 days of age,
      infants whose mothers received L. rhamnosus GG showed a significantly higher
      occurrence of B. breve and lower of B. adolescentis than those from the placebo
      group. In addition, L. rhamnosus GG consumption increased the bifidobacterial
      diversity in infants and reduced the Bifidobacterium microbiota similarity
      between mother and infant. CONCLUSIONS: These results indicate that specific
      changes in the transfer and initial establishment of bifidobacteria in neonates
      take place as consequence of the consumption of L. rhamnosus GG by the mothers.

PMID- 16456410
TI  - Clinical safety of Lactobacillus casei shirota as a probiotic in critically ill
      children.
AB  - OBJECTIVE: Diarrhea is frequently observed among critically ill children (CIC)
      admitted for intensive care. There is increasing evidence that probiotics
      decrease the incidence of acute infectious and nosocomial and antibiotic induced
      diarrhea amongst children hospitalized in nonintensive care settings. Despite
      theoretic advantages for the use of probiotics in CIC, safety has remained a
      concern in this vulnerable group. The objective of this study was to establish
      clinical safety (invasive infection/colonization) of Lactobacillus casei shirota
      (LCS) used as a probiotic in CIC. METHODS: Prospective, descriptive pilot study
      on children admitted to a pediatric intensive care unit. Data regarding safety
      were collected on the initial recruits to a randomized controlled trial aimed to
      study the effects of LCS on stool frequency and consistency in CIC. Safety was
      assessed by bacteriologic surveillance for LCS in surface swabs and endotracheal
      aspirates (colonization) as well as blood, urine, and sterile body fluid cultures
      (invasive infection/bacteremia). RESULTS: Safety data were available on 28
      patients. LCS was cultured from the feces of five of the six study subjects who
      opened bowels during their stay on the pediatric intensive care unit. There was
      no evidence of either colonization or bacteremia with LCS in bacteriologic
      cultures obtained from study subjects. The preparation was well tolerated with no
      apparent side effects. CONCLUSIONS: Our pilot safety study suggests that the use
      of LCS as a probiotic in enterally fed CIC is safe.

PMID- 16456411
TI  - A prospective study comparing oral sodium phosphate solution to a bowel cleansing
      preparation with nutrition food package in children.
AB  - OBJECTIVE: The inability of children to comply with bowel preparation regimens
      can result in inadequate visualization of the colon. This study compares the
      safety, efficacy, and patient acceptance of a prepackaged diet kit plus a
      magnesium citrate/bisacodyl bowel cleansing regimen with a clear liquid diet and
      sodium phosphate solution regimen in children undergoing colonoscopy. METHODS:
      Children scheduled for a diagnostic colonoscopy, were randomly assigned to
      receive a prepackaged diet kit and a magnesium citrate/bisacodyl laxative (group
      1), or clear liquids and sodium phosphate solution (group 2). The patients and
      their parents completed a questionnaire to evaluate acceptance of their assigned
      regimen before colonoscopy. The endoscopists, blinded to the type of bowel
      preparation, rated bowel cleansing. RESULTS: Sixty two children (28 males, 34
      females) with mean age 12.5 years participated. Thirty six and 26 patients were
      in groups 1 and 2 respectively. Overall cleansing was rated significantly
      superior in group 1 compared to group 2 as was amount of retained feces (P = .013
      for both). The overall frequency of reported side-effects was lower in group 1
      than (83.3%, 30/36) than in group 2 (100.0%, 26/26) (P = 0.03). The preparations
      were otherwise equivalent in regards to compliance and patient tolerance.
      CONCLUSIONS: Although both regimens were comparable in adequacy of colon
      visualization, preparation tolerance, side effects and compliance profile in this
      pilot study, the prepackaged diet kit with magnesium citrate/bisacodyl laxative
      resulted in superior colon cleansing.

PMID- 16456412
TI  - A dose determination study of polyethylene glycol 4000 in constipated children:
      factors influencing the maintenance dose.
AB  - OBJECTIVES: To determine the doses of polyethylene glycol (PEG) 4000 without
      additional salts allowing normal bowel habits in childhood functional
      constipation. METHODS: This multicenter noncomparative study allocated children
      to 4 groups: 6-12 months, 13 months-3 years, 4-7 years, and 8-15 years.
      Constipation was defined as <1 stool/d for more than 1 month in children aged 6
      12 months and <3 stools/w for more than 3 months in older children. Children
      randomly received either a nominal or a double starting dose. Treatment scheduled
      for 3 months could be adapted. Data were collected daily by the parents and rated
      at each visit by the investigator. RESULTS: In the 96 children included, the
      median (interquartile) effective daily doses were by groups; 3.75 (2.50-5.00) g,
      6.00 (4.00-7.43) g, 11.71 (7.00-16.00) g, and 16.00 (16.00-24.00) g,
      respectively, i.e., around 0.50 g/day/kg with a potential increment of the
      maintenance dose with higher initial dosages. More children had a final dosage
      identical to the initial one when started on the nominal dose (73%) than with the
      double one (42%, P < 0.003). More than 90% of children recovered normal bowel
      habits. Fecal soiling ceased in >60% of children with this symptom at enrolment.
      Fecal mass in the rectum and abdominal pain were markedly reduced and appetite
      improved. CONCLUSIONS: A daily dose of PEG 4000 around 0.50 g/day/kg in children
      aged 6 months to 15 years is effective in more than 90% of constipated children
      and 60% of those with fecal soiling.

PMID- 16456413
TI  - Incidence of Crohn disease in the Czech Republic in the years 1990 to 2001 and
      assessment of pediatric population with inflammatory bowel disease.
AB  - BACKGROUND: The aim of this study was to assess the pediatric population that
      suffered from inflammatory bowel disease (IBD) in the Czech Republic and to
      determine the incidence of Crohn disease (CD) in children up to 15 years age
      between 1990 and 2001. METHODS: Diagnostic criteria for CD, ulcerative colitis
      (UC), and indeterminate colitis (IC) were defined. Medical records provided a
      source of basic information about the children. A standardized protocol was
      filled out and sent to the coordinator of the study. All protocols were checked
      to see whether the data corresponded to the defined criteria and then were
      processed further. The study was retrospective in character for the years 1990 to
      1999 and prospective for the years 2000 and 2001. RESULTS: Diagnostic criteria
      were met in 470 patients with IBD; 201 of them turned 18 years old during the
      study period. CD was diagnosed in 223 patients. The incidence of CD in children
      up to 15 years of age increased from 0.25/100,000 in 1990 to 1.25/100,000 in
      2001. Eighty-two percent of children with CD were treated with aminosalicylates
      in combination with corticosteroids; 29% of patients received azathioprine.
      Severe growth retardation was recorded in 6.4% of adolescents with CD at the age
      of 18. UC was diagnosed in 202 patients. Therapy with aminosalicylates only was
      sufficient for control of the disease in 23% patients; 68% children were treated
      with corticosteroids, 15 of them (23% of the whole group) received additional
      azathioprine. Criteria for IC were met in 9.8% of all patients with IBD.
      CONCLUSION: This study confirmed an increase in incidence of CD in children
      younger than 15 years in the Czech Republic.

PMID- 16456414
TI  - Long-term prognosis of patients with biliary atresia: a 25 year summary.
AB  - OBJECTIVE: The purpose of this study was to delineate the long-term prognosis of
      biliary atresia (BA) in Taiwan. STUDY DESIGN: From 1976 to 2000, 185 children
      were diagnosed with BA, 22 underwent exploratory laparotomy without Kasai
      operation, and 163 underwent Kasai operation, of which 141 cases had long-term
      follow-up and formed the basis of this study. The outcome was analyzed. RESULTS:
      Among the 141 BA children studied who underwent Kasai operation, 115 (81.6%) had
      recoloration of stools, and 86 (61.0%) became jaundice-free (bilirubin <34
      micromol/L) [corrected]. The resolution of jaundice and the absence of repeated
      cholangitis contributed to better outcome. Five and 10 year survival rates with
      native liver were 35% and 31%, respectively. Liver transplantation was performed
      in 19 patients (all but 2 with a living-related donor), and 15 (79%) survived.
      Five and 10 year overall survival rates for BA patients were 41.9% and 40.2%,
      respectively. CONCLUSIONS: The study delineated the long-term outcome of BA in an
      Asian country other than Japan. Survival with native liver after a Kasai
      operation in Taiwan was similar to that in the American and European series.
      Limited donors for liver transplantation in the years of the study accounted for
      the poor overall prognosis of BA patients in this series.

PMID- 16456415
TI  - Endoscopic outcome beyond esophageal variceal eradication in children with
      extrahepatic portal venous obstruction.
AB  - OBJECTIVES: To find out the recurrence of esophageal varices, evolution of
      gastric varices, portal hypertensive gastropathy (PHG) and risk of rebleeding
      following esophageal variceal eradication. METHODS: Between 1992 and 2002,
      children with extrahepatic portal venous obstruction (EHPVO) and bleeding from
      esophageal varices received endoscopic injection sclerotherapy until eradication.
      Surveillance endoscopy was performed initially at 3 months and subsequently at
      intervals of 6 months to one year to detect esophageal and gastric varices, and
      PHG. Gastric varices were classified as gastroesophageal (GOV) or isolated
      gastric varices (IGV). Gastroesophageal varices included types GOV1 and GOV2 that
      extend along lesser and greater curvatures respectively. Patients who had
      recurrence of bleeding were evaluated by emergency upper gastrointestinal
      endoscopy. RESULTS: 163 of 183 children who achieved esophageal variceal
      eradication were evaluated. Esophageal varices recurred in 40% cases. Primary
      gastric varices (before sclerotherapy) were seen in 61% cases [GOV 98% (83% GOV1,
      15% GOV2) and IGV 2%] and secondary (after sclerotherapy) in 28% [GOV 71% (47%
      GOV1, 24% GOV2) and IGV 29%]. Secondary gastric varices were distributed as 20%
      GOV1, 42% GOV2 and 87% IGV. Frequency of gastric varices before sclerotherapy and
      at the last follow up showed decrease in GOV1 from 82 to 56 (P = 0.02), increase
      in GOV2 from 15 to 23 and increase in IGV from 2 to 15 (P < 0.001). PHG increased
      in frequency from 12% to 41% (P < 0.001) and severity from one patient to 12 (P <
      0.001). Eleven cases had rebleeding from gastric varices (5 GOV1, 4 GOV2 and 2
      IGV). CONCLUSIONS: Following esophageal variceal eradication in children with
      EHPVO a significant decrease in GOV1, increase in IGV and increased frequency and
      severity of PHG takes place. Small rebleeding risk persists from gastric varices
      irrespective of the type.

PMID- 16456416
TI  - Liver abscesses in children: a single center experience in the developed world.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical and radiologic
      features, predisposing risk factors, and complications of children with pyogenic
      liver abscess (PLA) referred to a tertiary pediatric hepatology center. METHODS:
      We analyzed our database of all children referred to our unit over a 10 year
      period and performed a case note review of all patients with a radiologically
      proven PLA. RESULTS: PLA was diagnosed in 15 children (7 boys), 0.5% of all
      referrals. They presented at a median age of 10 years (range 2 months-15 years).
      In three children (2 boys), PLA was the first manifestation of chronic
      granulomatous disease. Among the others, five had radiologic evidence of other
      intra-abdominal pathology (1 with subsequently proven appendicitis), and four
      developed portal vein thrombosis with portal hypertension. The commonest isolated
      pathogen was Staphylococcus aureus. Combined treatment with guided aspiration and
      prolonged intravenous antibiotics was successful in all patients. CONCLUSION: PLA
      is a rare diagnosis in children in the developed world. It may be caused by
      primary neutrophil disorders even in the absence of a previous history of
      infection. Co-existent appendicitis, intra-abdominal sepsis, and ascending
      pylephlebitis must be sought because these children are at risk of developing
      portal vein obstruction and portal hypertension. Prolonged intravenous antibiotic
      treatment guided by microbiologic sensitivities is highly effective.

PMID- 16456417
TI  - Meat as a first complementary food for breastfed infants: feasibility and impact
      on zinc intake and status.
AB  - OBJECTIVE: This study was undertaken to assess the feasibility and effects of
      consuming either meat or iron-fortified infant cereal as the first complementary
      food. METHODS: Eighty-eight exclusively breastfed infants were enrolled at 4
      months of age and randomized to receive either pureed beef or iron-fortified
      infant cereal as the first complementary food, starting after 5 months and
      continuing until 7 months. Dietary, anthropometric, and developmental data were
      obtained longitudinally until 12 months, and biomarkers of zinc and iron status
      were measured at 9 months. RESULTS: Mean (+/-SE) daily zinc intake from
      complementary foods at 7 months for infants in the meat group was 1.9 +/- 0.2 mg,
      whereas that of the cereal group was 0.6 +/- 0.1 mg, which is approximately 25%
      of the estimated average requirement. Tolerance and acceptance were comparable
      for the two intervention foods. Increase in head circumference from 7 to 12
      months was greater for the meat group, and zinc and protein intakes were
      predictors of head growth. Biochemical status did not differ by feeding group,
      but approximately 20% of the infants had low (<60 microg/dL) plasma zinc
      concentrations, and 30% to 40% had low plasma ferritin concentrations (<12
      microg/L). Motor and mental subscales did not differ between groups, but there
      was a trend for a higher behavior index at 12 months in the meat group.
      CONCLUSIONS: Introduction of meat as an early complementary food for exclusively
      breastfed infants is feasible and was associated with improved zinc intake and
      potential benefits. The high percentage of infants with biochemical evidence of
      marginal zinc and iron status suggests that additional investigations of optimal
      complementary feeding practices for breastfed infants in the United States are
      warranted.

PMID- 16456418
TI  - Free sugar and sugar alcohol concentrations in human breast milk.
AB  - OBJECTIVES: The goal was to determine the free sugars and polyols in human breast
      milk, both term and preterm, for comparison with formula milks. METHODS:
      Methodology was developed for the measurement of the free sugars and polyols in
      breast milk. There were 16 samples collected from women who delivered at term and
      17 samples from women delivering preterm. For purposes of comparison, samples
      were also collected from four commercial formulas for term infants and eight from
      commercial formulas for preterm infants as well as one sample of cows' milk. All
      samples were frozen immediately and analyzed by high-performance liquid
      chromatography techniques. RESULTS: Except for lactose concentrations, no
      significant differences were detected for all other sugars and polyols between
      term and preterm breast milk samples. Within breast milk samples, two patterns
      emerged, with one group containing additional elution peaks for compounds not yet
      identified. A second group did not contain these compounds. There were a number
      of significant differences between breast milk and formulas, particularly for
      inositol, glycerol, glucose, and galactose. All milks contained significant
      concentrations of mannose. CONCLUSIONS: There are no significant differences
      among breast milk samples for free sugar and polyol concentrations except
      lactose. However, some milk contains additional peaks that could be of dietary or
      genetic origin. Formula milk has relatively high concentrations of glucose and
      galactose compared with breast milk, suggesting some lactose hydrolysis.

PMID- 16456419
TI  - Long term nutritional rehabilitation by gastrostomy in Israeli patients with
      cystic fibrosis: clinical outcome in advanced pulmonary disease.
AB  - OBJECTIVES: Several studies have shown a linear correlation between nutritional
      status and pulmonary function in patients with cystic fibrosis. Our study aims
      were: 1) To evaluate the effect of nutritional supplementation via gastrostomy on
      nutritional, clinical, and pulmonary parameters, and 2) To identify predicting
      factors for success of long-term nutritional rehabilitation. METHODS: Twenty-one
      Israeli patients, aged 8 months to 20 years, underwent gastrostomy insertion from
      1992 to 2001. All patients were pancreatic insufficient, and all carried severe
      mutations (W1282X in 62% of the patients). Anthropometric and clinical data were
      obtained for each patient: 0-12 months before and 6-12 months and 18-24 months
      after gastrostomy placement. Standard deviation scores (SDS) for height, weight,
      and body mass index as well as percent of height-appropriate body weight were
      calculated. RESULTS: The mean percent-of-predicted forced expiratory volume in 1
      second (FEV1) decreased significantly during the first year of gastrostomy
      feeding (n = 16), from 44.2% +/- 13.9 to 41% +/- 13.3 (P = 0.05). However, during
      the second year of therapy (n = 10), a trend toward improvement was observed
      (from 39.4 +/- 12.1 to 41.4 +/- 16.1). Weight, and BMI z-scores as well as weight
      percent-of ideal body weight increased significantly. Height z-score for age
      decreased during the first year (from -1.9 +/- 1.3 to -2.1 +/- 1.4), However, a
      trend toward improvement was observed during the second year. A significant
      correlation was found between the change in weight z-score and height z-score
      during the first (r = 0.488, P = 0.016) and the second (r = 0.825, P < 0.001)
      years. There was no difference between compliers and noncompliers regarding
      height, weight, and BMI either before or after gastrostomy placement. A
      significant correlation between age at insertion of gastrostomy and improvement
      in height z-score (r = 0.52, P = 0.016) was observed. Cystic fibrosis related
      diabetes (n = 8) did not affect the response to supplemental feeding.
      CONCLUSIONS: We observed a trend toward improvement of pulmonary disease during
      the second year, and a significant improvement in weight, height, and BMI z
      scores. Compliance, diabetes, and young age prior to tube insertion did not
      predict success of nutritional rehabilitation.

PMID- 16456420
TI  - Ulcerative esophagitis: a complication of a self-expanding metal-stent in a
      child.

PMID- 16456421
TI  - Minocycline-induced autoimmune hepatitis with subsequent cirrhosis.

PMID- 16456422
TI  - Crigler-Najjar syndrome type II caused by a homozygous triple mutation [T-3279G,
      A(TA)7TAA, and H39D] of UGT1A1.

PMID- 16456423
TI  - Capsule endoscopy in pediatric patients with hamartomatous polyp syndromes.

PMID- 16456424
TI  - Re: Gastrointestinal outcomes and confounders in cystic fibrosis.

PMID- 16456425
TI  - A girl with a (wrongly-located) golden heart.

PMID- 16456428
TI  - Clinical quiz: gastric teratoma.

PMID- 16456427
TI  - Management of fulminating ulcerative colitis in childhood with chimeric anti-CD25
      antibody.
AB  - Fulminating acute ulcerative colitis (UC) is a potentially life threatening
      medical emergency. Up to 30% of individuals respond poorly to corticosteroids
      alone and second line medical or surgical therapies are indicated. We describe
      the successful use of chimeric anti-CD25 therapy in 4 such children poorly
      responsive to combined therapy with intravenous steroids and calcineurin
      inhibitors with a pretreatment predictive risk of colectomy of 85-100%. Clinical
      disease activity scores normalized within 72 hours of anti-CD25 administration
      and colonic histology provided evidence of mucosal healing within 10-14 days.
      None required emergency colectomy. Anti-CD25 is efficacious in fulminating UC and
      randomized placebo controlled trials appear indicated.

PMID- 16456429
TI  - How then shall we change?

PMID- 16456430
TI  - The shape of things to come: results from a national survey of trauma surgeons on
      issues concerning their future.
AB  - BACKGROUND: This study seeks to characterize the opinions of practicing surgeons
      as a basis for formulating a plan to restructure the discipline of trauma surgery
      and its training path. METHODS: A 52-item questionnaire was administered to the
      membership of the American Association for the Surgery of Trauma, the Eastern
      Association for the Surgery of Trauma, and the Western Trauma Association. The
      survey tool investigated issues related to current and future practice. RESULTS:
      Response rate was 60%. Mean age was 49 years and 88% were male. The average time
      in practice is 15 years. The average workweek is 80 hours with 48% of that time
      devoted to clinical practice. About half take in-house call and about one-third
      receive an on-call stipend. The median annual number of major trauma cases was
      50. The most important disincentives to entering the field were felt to be
      lifestyle issues and a limited scope of practice. Almost 90% felt their work as
      trauma surgeons was undervalued by society and the health care system. The great
      majority (88%) responded that the discipline of trauma surgery must change.
      Respondents feel this restructuring should include broader general surgery (83%)
      as well as limited orthopedic (60%) and neurosurgical trauma-related procedures
      (59%). About one-half of respondents favored in-house call (54%) and a practice
      model similar to emergency medicine (55%). Factors that would most enhance
      practice were thought to be guaranteed appropriate salary and guaranteed time
      away from work. Training in a broad range of skills was felt to be essential or
      useful to the trauma surgeon of the future, although few currently employ such a
      wide breadth of skills. CONCLUSIONS: Current practicing trauma surgeons feel that
      the discipline must change to remain viable. This change should entail broader
      training to allow more procedures in trauma, emergency surgery, critical care,
      and elective general surgery. The preferred practice model is a large, hospital
      based, diversified group practice with a predictable lifestyle and guaranteed
      salary commensurate with effort. Inclusion of selected emergency orthopedic and
      neurosurgical procedures are viewed favorably, as is in-house call. Efforts to
      increase public perception of trauma surgery's value to society and its impending
      demise are warranted.

PMID- 16456431
TI  - Early aggressive closure of the open abdomen.
AB  - BACKGROUND: The aim of this series is to describe a new and aggressive approach
      to definitive closure of the open abdomen. METHODS: A retrospective review of 37
      patients who underwent definitive abdominal closure using a combination of vacuum
      pack, vacuum-assisted wound management and human acellular dermal matrix (HADM).
      RESULTS: All patients' open abdomens were maintained with vacuum assisted wound
      management in attempts for primary closure. Once it was determined that the
      abdomen would not close primarily; it was closed with HADM and skin advancement.
      The mean duration of the open abdomen was 21.7 days (range 6-45), with an average
      of 127.78 cm of HADM, the largest number being 800 cm, with decreasing use of
      product later in the series. No major complications were seen with the repair.
      Superficial wound infection occurred with two patients that were easily treated
      with wet to dry dressing changes. No intraabdominal complications such as fistula
      or graft loss were seen. All patients left the hospital with an intact abdominal
      wall and skin. All 37 patients survived to discharge and were seen in follow-up
      within one month. No early hernia formation was seen at the one month follow up
      with the longest at three years. No abdominal wall complications were seen in
      subsequent follow up patients. CONCLUSIONS: Early aggressive closure of the open
      abdomen is possible with a combination of vacuum pack, vacuum-assisted wound
      management and HADM. Short term results are promising and warrant further study.

PMID- 16456432
TI  - Cystogram follow-up in the management of traumatic bladder disruption.
AB  - BACKGROUND: The utility of obtaining a routine cystogram after the repair of
      intraperitoneal bladder disruption before urethral catheter removal is unknown.
      This study was designed to examine whether follow-up cystogram evaluation after
      traumatic bladder disruption affected the clinical management of these injuries.
      We hypothesized that routine cystograms, after operative repair of
      intraperitoneal bladder disruptions, provide no clinically useful information and
      may be eliminated in the management of these injuries. METHODS: Our prospectively
      collected trauma database was retrospectively reviewed for all ICD-9 867.0 and
      867.1 coded bladder injuries over a 6-year period ending in June 2004.
      Demographics, clinical injury data, detailed operative records, and imaging
      studies were reviewed for each patient. Bladder injuries were categorized as
      intraperitoneal (IP) or extraperitoneal (EP) bladder disruptions based on imaging
      results and operative exploration. Patients with IP injuries were further
      subdivided into those with "simple" dome disruptions or through-and-through
      penetrating injuries and "complex" injuries involving the trigone or ureter
      reimplantation. All patients sustaining isolated ureteric or urethral injury were
      excluded from further analysis. RESULTS: In all, 20,647 trauma patients were
      screened for bladder injury. Out of this group, there were 50 IP (47 simple, 3
      complex) and 37 EP injuries available for analysis. All IP injuries underwent
      operative repair. Eight of the IP injuries (all simple) had no postoperative
      cystogram and all were doing well at 1- to 4-week follow-up. The remaining 42
      patients underwent a postoperative cystogram at 15.3 +/- 7.3 days (range 7 to 36
      days). All simple IP injuries had a negative postoperative cystogram. The only
      positive study was in one of the three complex IP injuries. In the EP group,
      21.6% had positive cystograms requiring further follow-up and intervention.
      CONCLUSIONS: Patients sustaining extraperitoneal and complex intraperitoneal
      bladder disruptions require routine cystogram follow-up. In those patients
      undergoing repair of a simple intraperitoneal bladder disruption, however,
      routine follow-up cystograms did not affect clinical management. Further
      prospective evaluation to determine the optimal timing of catheter removal in
      this patient population is warranted.

PMID- 16456433
TI  - Trauma center brief interventions for alcohol disorders decrease subsequent
      driving under the influence arrests.
AB  - BACKGROUND: A substantial number of trauma center admissions are related to
      driving under the influence (DUI); however, there has been no prior report of
      brief intervention (BI) after injury reducing subsequent DUI arrests. The
      hypothesis of this study was that injured patients receiving BI would have a
      lower risk of DUI arrest within 3 years of discharge than those receiving
      standard care (SC). METHODS: This prospective, randomized clinical trial randomly
      allocated patients involved in motor vehicle collisions to receive SC or a BI
      regarding alcohol use. The primary outcome measure was DUI arrest within 3 years
      of hospital discharge. DUI arrests were documented by matching demographic
      information to state traffic safety data. RESULTS: After randomization (N = 126),
      BI and SC groups were similar in age, prior DUI arrests, and alcohol screening
      score. BI sessions lasted an average of 30 minutes and were performed by either a
      social worker or a trauma surgeon. Approximately one in six participants (n = 21,
      16.7%) had a DUI arrest within 3 years of hospital discharge. Within 3 years of
      hospital discharge, 14 of 64 patients (21.9%) in the SC group had an arrest for
      DUI compared with only 7 of 62 patients (11.3%) who received the BI. Multivariate
      analysis demonstrated that BI was the strongest protective factor against DUI
      arrest (odds ratio [OR], 0.32; 95% confidence interval < or =CI], 0.11-0.96).
      Prior number of DUIs (OR, 1.43; 95% CI, 1.03-2.01) and age (OR, 0.94; 95% CI,
      0.88-0.99) were also associated with DUI arrest post-hospitalization, but alcohol
      screening score (OR, 1.06; 95% CI, 0.99-1.13) was not. The absolute risk
      reduction implies that only nine patients would need to receive a BI to prevent
      one DUI arrest. CONCLUSION: Patients who receive BI during a trauma center
      admission are less likely to be arrested for DUI within 3 years of discharge. BI
      represents a viable intervention to reduce DUI after trauma center admission.

PMID- 16456434
TI  - Retrievable vena cava filters for preventing pulmonary embolism in trauma
      patients: a cautionary tale.
AB  - BACKGROUND: Retrievable vena cava filters (RFs) offer the appeal of short-term
      prophylaxis for trauma patients temporarily at risk for pulmonary embolism (PE)
      without the long-term risks of permanent vena cava filters (PFs). However, the
      evidence that RFs and PFs reduce the risks of PE and death in trauma patients is
      not conclusive. RFs were introduced at our trauma center in August 2002. The
      purpose of this study was to evaluate the effects of RFs on our strategy to
      prevent PE in trauma patients. METHODS: We reviewed our trauma registry to
      compare rates of filter placement, filter-related complications (FRCs), and PE
      before (Group I: January 2000 to August 15, 2002) and after (Group II: August 16,
      2002 through December 2004) RF introduction. Indication for filter placement,
      filter retrieval, FRCs, and incidence of PE were compared. RESULTS: There were
      5,042 patients in Group I and 5,038 patients in Group II. There was a threefold
      increase in filter placement in Group II compared with Group I (55 [1.1%] versus
      161 [3.2%]; p < 0.001). There were no significant differences between the rates
      of PE (0.2% versus 0.2%, p = 0.636) or major FRCs (1.8% versus 2.5%, p = 0.777).
      Major FRCs included two filter infections with sepsis, one vena cava thrombotic
      occlusion, one filter lodged in the jugular vein during retrieval, and one PE
      after filter placement. RF removal was attempted in 43 (27%) patients and
      successful in 33 (21%). CONCLUSION: The advent of RFs was associated with a
      threefold increase in vena cava filter placement in our trauma center. Major FRCs
      were encountered and a very low incidence of PE was not altered by their use.
      Successful removal could be verified in only 21% of RFs. The results of this
      study lead us to question the rationale for a more liberal use of vena cava
      filters in trauma patients.

PMID- 16456435
TI  - HSPTX protects against hemorrhagic shock resuscitation-induced tissue injury: an
      attractive alternative to Ringer's lactate.
AB  - BACKGROUND: Conventional fluid resuscitation with Ringer's lactated (RL)
      activates neutrophils and causes end-organ damage. We have previously shown that
      HSPTX, a combination of small volume hypertonic saline (HS) and pentoxifylline
      (PTX), a phosphodiesterase-inhibitor, downregulates in vitro neutrophil
      activation and proinflammatory mediator synthesis. Herein, we hypothesized that
      HSPTX decreases end-organ injury when compared with RL in an animal model of
      hemorrhagic shock. METHODS: Sprague-Dawley rats were bled to a mean arterial
      pressure of 35 mm Hg for 1 hour. Animals were divided into 3 groups: sham (no
      shock, no resuscitation, n = 7), RL (32 mL/kg, n = 7), and HSPTX (7.5% NaCl 4
      mL/kg + PTX 25 mg/kg; n = 7). Shed blood was infused after fluid resuscitation.
      Blood pressure was monitored until the end of resuscitation. Animals were
      sacrificed at 24 hour after resuscitation. Bronchoalveolar lavage fluid (BALF)
      was obtained for white cell count (total and differential) and TNF-alpha and IL
      1beta levels were measured by ELISA. Lung and intestinal injury at 24 hour were
      evaluated by histopathology. Organ damage was graded by a pathologist and a score
      was created (0 = no injury; 3 = severe). Lung neutrophil infiltration was
      evaluated by MPO immune staining. RESULTS: There were no differences in mean
      arterial pressure between groups. At 24 hours, BALF leukocyte count was decreased
      by 30% in HSPTX animals (p < 0.01). TNF-alpha and IL-1beta levels were markedly
      decreased in HSPTX-resuscitated animals compared with their RL counterparts (p <
      0.01). HSPTX-resuscitated animals (lung injury score = 1.0 +/- 0.4) had markedly
      decreased acute lung injury compared with RL-treated animals (2.5 +/- 0.3) (p <
      0.01). RL resuscitation led to a two-fold increase in lung neutrophil
      infiltration whereas in HSPTX-treated animals, the number of MPO + cells was
      similar to sham animals (p < 0.001). Intestinal injury was markedly attenuated by
      HSPTX (1.1 +/- 0.3) compared with RL animals (2.6 +/- 0.4) (p < 0.001).
      CONCLUSIONS: HSPTX, a small volume resuscitation strategy with marked
      immunomodulatory potential led to a marked decrease in end-organ damage. HSPTX is
      an attractive alternative to RL in hemorrhagic shock resuscitation.

PMID- 16456436
TI  - Hepatic and pulmonary apoptosis after hemorrhagic shock in swine can be reduced
      through modifications of conventional Ringer's solution.
AB  - BACKGROUND: Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's
      solution detected in vitro and in small animal experiments, have not been
      confirmed in large animal models. Our hypothesis was that in a clinically
      relevant large animal model of hemorrhage, resuscitation with racemic lactated
      Ringer's solution would induce cellular apoptosis, which can be attenuated by
      elimination of d-lactate. METHODS: Yorkshire swine (n = 49, weight 40-58 kg) were
      subjected to uncontrolled (iliac arterial and venous injuries) and controlled
      hemorrhage, totaling 40% of estimated blood volume. They were randomized (n =
      7/group) to control groups, which consisted of (1) no hemorrhage (NH), (2) no
      resuscitation (NR), or resuscitation groups, which consisted of (3) 0.9% saline
      (NS), (4) racemic lactated Ringer's (DL-LR), (5) L-isomer lactated Ringer's (L
      LR), (6) Ketone Ringer's (KR), (7) 6% hetastarch in 0.9% saline (Hespan). KR was
      identical to LR except for equimolar substitution of lactate with beta
      hydroxybutyrate. Resuscitation was performed in three phases, simulating (1)
      prehospital, (2) operative, (3) postoperative/recovery periods. Arterial blood
      gasses, circulating cytokines (TNF-alpha, IL-1, -6, -10), and markers of organ
      injury were serially measured. Metabolic activity of brain, and liver, was
      measured with microdialysis. Four hours postinjury, organs were harvested for
      Western blotting, ELISA, TUNEL assay, and immunohistochemistry. RESULTS: All
      resuscitation strategies restored blood pressure, but clearance of lactic
      acidosis was impeded following DL-LR resuscitation. Metabolic activity decreased
      during shock and improved with resuscitation, without any significant inter-group
      differences. Levels of cytokines in circulation were similar, but tissue levels
      of TNF in liver and lung increased six- and threefolds (p < 0.05) in NR group. In
      liver, all resuscitation strategies significantly decreased TNF levels compared
      with the NR group, but in the lung resuscitation with lactated Ringer (DL and L
      isomers) failed to decrease tissue TNF levels. DL-LR resuscitation also increased
      apoptosis (p < 0.05) in liver and lung, which was not seen after resuscitation
      with other solutions. CONCLUSIONS: In this large animal model of hemorrhagic
      shock, resuscitation with conventional (racemic) LR solution increased apoptotic
      cell death in liver and lung. This effect can be prevented by simple elimination
      of D-lactate from the Ringer's solution.

PMID- 16456438
TI  - Elevated orbital pressure: another untoward effect of massive resuscitation after
      burn injury.
AB  - BACKGROUND: Fluid resuscitation remains a fundamental component of early burn
      care management. However, recent studies suggest that excessive volumes of
      resuscitation are being administered. Overresuscitation results in negative
      sequelae including abdominal and extremity compartment syndromes. Elevated
      intraocular pressure (IOP) has been described as another potentially devastating
      effect of massive fluid resuscitation in trauma patients. The orbit, similar to
      the abdomen and extremity, is a compartment, limited to expansion from edema
      anteriorly by the eyelids and orbital septum, and posteriorly by the bony orbital
      walls. The purpose of this study was to review the incidence of elevated IOP in a
      series of patients with major burn injury. METHODS: We retrospectively reviewed
      the charts of 13 consecutive patients admitted to our burn center with burn sizes
      >25% total body surface area (TBSA). All patients underwent serial IOP
      measurements for the first 72 hours following admission. Medical records were
      reviewed for fluid resuscitation volume, IOP measurements, need for canthotomy,
      and results of canthotomy procedures. RESULTS: Five of 13 patients had IOP >30 mm
      Hg and required lateral canthotomy. Canthotomy immediately reduced IOP (p =
      0.009). Patients who developed elevated IOP received a significantly larger fluid
      resuscitation (9.0 cc/kg/%TBSA versus 6.0 cc/kg/%TBSA, p = 0.02). Elevated IOP
      was significantly associated with delivery of larger fluid resuscitation volume
      (p = 0.027). CONCLUSIONS: Massive fluid resuscitation following burn injury can
      result in orbital compartment syndrome requiring lateral canthotomy. Early
      diagnosis and treatment of orbital compartment syndrome should be incorporated
      into the management of patients with major burn injury receiving large fluid
      resuscitation volume.

PMID- 16456437
TI  - Hypertonic lactated saline resuscitation reduces the risk of abdominal
      compartment syndrome in severely burned patients.
AB  - BACKGROUND: Secondary abdominal compartment syndrome is a lethal complication
      after resuscitation from burn shock. Hypertonic lactated saline (HLS) infusion
      reduces early fluid requirements in burn shock, but the effects of HLS on
      intraabdominal pressure have not been clarified. METHODS: Patients admitted to
      our burn unit between 2002 and 2004 with burns > or =40% of the total body
      surface area without severe inhalation injury were entered into a fluid
      resuscitation protocol using HLS (n = 14) or lactated Ringer's solution (n = 22).
      Urine output was monitored hourly with a goal of 0.5 to 1.0 mL/kg per hour.
      Hemodynamic parameters, blood gas analysis, intrabladder pressure as an indicator
      of intraabdominal pressure (IAP), and the peak inspiratory pressure were
      recorded. Pulmonary compliance and the abdominal perfusion pressure were also
      calculated. RESULTS: In the HLS group, the amount of intravenous fluid volume
      needed to maintain adequate urine output was less at 3.1 +/- 0.9 versus 5.2 +/-
      1.2 mL/24 h per kg per percentage of total body surface area, and the peak IAP
      and peak inspiratory pressure at 24 hours after injury were significantly lower
      than those in the lactated Ringer's group. Two of 14 patients (14%) in the HLS
      group and 11 of 22 patients (50%) developed IAH within 20.8 +/- 7.2 hours after
      injury. CONCLUSION: In patients with severe burn injury, a large intravenous
      fluid volume decreases abdominal perfusion during the resuscitative period
      because of increased IAP. Our data suggest that HLS resuscitation could reduce
      the risk of secondary abdominal compartment syndrome with lower fluid load in
      burn shock patients.

PMID- 16456439
TI  - Implementation of a norepinephrine-based protocol for management of septic shock:
      a pilot feasibility study.
AB  - BACKGROUND: The subject of the best vasopressor for hemodynamic management of
      septic shock (SS) is controversial. One of the difficulties in planning such
      studies is that physicians are reluctant to use one vasopressor exclusively, and
      there is considerable variation in practice. The aim of this study was to test
      the feasibility of implementing a single pressor-based algorithm (in this case,
      norepinephrine [NE]). METHODS: A NE-based algorithm was applied prospectively to
      100 consecutive SS patients. A formal training program was implemented before
      starting the protocol and applied to 72 physicians and nurses involved in
      intensive care unit (ICU) patient care. Compliance, protocol violations, probable
      adverse effects, and outcome were evaluated on a daily basis by an independent
      group of fellows and a research nurse. RESULTS: In 100 patients, there were 7,139
      hours of algorithm use. Only 13 protocol violations were observed, mostly in the
      timing of inotropic drugs. Senior staff physicians or busy night shifts accounted
      for most of these violations. ICU mortality was 33%, which is comparable to that
      predicted by Acute Physiology and Chronic Health Evaluation II and Sequential
      Organ Failure Assessment scores. Adverse events probably related to NE were not
      observed. CONCLUSIONS: The present algorithm, applied after a strict training
      program, obtained an overall good acceptance and compliance with very few
      protocol violations in more than 7,000 hours of use. Safety was demonstrated by a
      global mortality comparable to that predicted by severity scores and absence of
      specific drug-related morbidity. The implementation of a single pressor-based
      algorithm for SS is feasible and safe.

PMID- 16456440
TI  - Outcome prediction by a mathematical model based on noninvasive hemodynamic
      monitoring.
AB  - BACKGROUND: The aims are to apply a mathematical search and display model based
      on noninvasive hemodynamic monitoring, to predict outcome early in a
      consecutively monitored series of 661 severely injured patients. METHODS: A
      prospective observational study by a previously designed protocol in a Level I
      trauma service in a university-run inner city public hospital was conducted. The
      survival probabilities were calculated at the initial resuscitation on admission
      and at subsequent intervals during their hospitalization beginning shortly after
      admission to the emergency department. Cardiac function was evaluated by cardiac
      output (CI), heart rate (HR), and mean arterial blood pressure (MAP), pulmonary
      function by pulse oximetry (SapO2), and tissue perfusion function by
      transcutaneous oxygen indexed to FiO2, (PtcO2/FiO2), and carbon dioxide (PtcCO2)
      tension. RESULTS: The survival probability (SP) averaged 89 +/- 0.4% for
      survivors and 75.7 +/- 1.6% (p < 0.001) for nonsurvivors in the first 24-hour
      period of resuscitation. The CI, MAP, SapO2, PtcO2, and PtcO2/FiO2 were
      significantly higher in survivors than in nonsurvivors in initial resuscitation,
      whereas HR and PtcCO2 were higher in nonsurvivors. CONCLUSIONS: During the
      initial resuscitation period, misclassifications were 102 of 661 or 15%. The SP
      provided early objective criteria to evaluate hospital outcome and to track
      changes throughout the hospital course based on a large database of patients with
      similar clinical-hemodynamic states.

PMID- 16456441
TI  - Tracheostomy in ventilator dependent trauma patients: a prospective, randomized
      intention-to-treat study.
AB  - BACKGROUND: Tracheostomy is a commonly performed procedure in ventilator
      dependent patients. Many critical care practitioners believe that performing a
      tracheostomy early in the postinjury period decreases the length of ventilator
      dependence as well as having other benefits such as better patient tolerance and
      lower respiratory dead space. We conducted a randomized, prospective, single
      institution study comparing the length ventilator dependence in critically ill
      multiple trauma patients who were randomized to two different strategies for
      performance of a tracheostomy. We hypothesized that earlier tracheostomy would
      reduce the number of days of mechanical ventilation, frequency of pneumonia and
      length of intensive care unit (ICU) stay. METHODS: Patients were eligible if they
      were older than 15 years and either a Glasgow Coma Score (GCS) >4 with a negative
      brain computed tomography (CT) (no anatomic head injury), or a GCS >9 with a
      positive head CT (known anatomic head injury). Patients who required tracheostomy
      for facial/neck injuries were excluded. Patients were randomized to an intention
      to treat strategy of tracheostomy placement before day 8 or after day 28.
      RESULTS: The study was halted after the first interim analysis. There were 60
      enrolled patients, who had comparable demographics between groups. There was no
      significant difference between groups in any outcome variable including length of
      ventilator support, pneumonia rate, or death. CONCLUSION: A strategy of
      tracheostomy before day 8 postinjury in this group of trauma patients did not
      reduce the number of days of mechanical ventilation, frequency of pneumonia or
      ICU length of stay as compared with the group with a tracheostomy strategy
      involving the procedure at 28 days postinjury or more.

PMID- 16456442
TI  - National nosocomial infection surveillance system: from benchmark to bedside in
      trauma patients.
AB  - INTRODUCTION: Ventilator-associated pneumonia (VAP) is an important cause of
      morbidity and mortality in the injured patient. Identification of those with VAP
      is important both in immediate clinical decision making as well as for the
      epidemiologic evaluation of the disease and benchmarking of rates across
      institutions with variable practice patterns. Despite this, controversy exists
      over the optimal method of VAP diagnosis. Many centers currently use invasive
      culture methods such as bronchoalveolar lavage (BAL) for diagnosis. Another
      diagnostic method, and the most common epidemiologic tool used to track VAP, is
      the definition employed by the National Nosocomial Infections Surveillance (NNIS)
      system. This relies on a combination of clinical and culture data. Our goal was
      to evaluate the accuracy of the NNIS definition as compared with BAL diagnosis in
      trauma patients. METHODS: Records of all ventilated patients admitted to the
      trauma intensive care unit at a Level I center who were evaluated for the
      presence of pneumonia over a 2.5-year period were reviewed. VAP diagnosis was
      established if > or =10 cfu/mL were cultured on BAL. VAP rates and time of onset
      were compared with the hospital infection control database, which defines VAP by
      NNIS criteria. Assuming BAL to be correct, sensitivity, specificity, and positive
      and negative predictive values were calculated for NNIS VAP. RESULTS: From
      September 1, 2001, through December 31, 2003, 292 patients underwent BAL for
      suspected pneumonia. The pneumonia rate in this group was 34 per 1,000 ventilator
      days. The NNIS definition showed excellent overall agreement, with a rate of 36
      per 1,000 ventilator days. The use of the NNIS definition for bedside decision
      making, however, is less accurate. Sensitivity and positive predictive value were
      reasonably good (84% and 83%, respectively), whereas specificity and negative
      predictive value suffer (69% and 69%, respectively). Most importantly, the use of
      NNIS would have led to no treatment in 16% of patients diagnosed with VAP by BAL.
      CONCLUSIONS: Compared with strict bacteriologic criteria for VAP, the NNIS
      definition has good overall agreement and seems to have utility as an
      epidemiologic benchmarking tool in trauma patients. However, the NNIS definition
      has less utility as a bedside decision-making tool in this population, leading to
      under-treatment in a significant number of patients.

PMID- 16456443
TI  - Ventilator-associated pneumonia, like real estate: location really matters.
AB  - INTRODUCTION: Previous work has demonstrated an increased risk of ventilator
      associated pneumonia (VAP) in trauma patients after prehospital (field)
      intubation as compared with emergency department (ED) intubations. However, this
      population was not compared with patients intubated as inpatients, making data
      interpretation difficult. We sought to further examine predictors for the
      development of VAP after trauma. METHODS: A 10-year retrospective review of all
      patients mechanically ventilated greater than 24 hours after injury was
      performed. RESULTS: In all, 1,628 patients were identified, of which 1,213 (75%)
      were intubated as inpatients and 415 were emergently intubated (353 ED, 62
      field). Overall, those intubated emergently were younger (p = 0.03) and less
      injured as seen by higher Glasgow Coma Scale scores (p = 0.0002), lower Injury
      Severity Scores (p = 0.01) and higher Revised Trauma Scores (p < 0.0001). Despite
      a lower injury severity, those patients emergently intubated were more likely to
      develop pneumonia as 22% of ED intubations and 15% of field intubations developed
      pneumonia, as compared with the inpatient rate of 6.5%. Pneumonia after field
      intubation was more likely to be community-acquired (p < 0.0001) with a
      significantly lower percentage of infecting enteric gram-negative rods (p <
      0.0001) as compared with the inpatient and ED groups. Forward logistic regression
      analysis (with VAP = 1) identified inpatient intubation as protective against VAP
      (odds ratio 0.28, 95% CI = 0.2-0.4). Backwards logistic regression analysis
      further identified both field airway (odds ratio 2.29, 95% CI = 1.1-4.9) and ED
      airway (odds ratio 3.61, 95% CI = 2.5-5.2) as predictive of VAP. CONCLUSIONS:
      Compared with a population of trauma patients as inpatients, and excluding those
      patients mechanically ventilated less than 24 hours, patients intubated in the ED
      or field have a higher incidence of pneumonia, despite equivalent or lower injury
      severity.

PMID- 16456444
TI  - Thoracoscopic application of a topical sealant for the management of persistent
      posttraumatic pneumothorax.
AB  - BACKGROUND: Persistent posttraumatic pneumothorax (PPP) is an uncommon
      complication of blunt or penetrating chest trauma. Currently, most patients are
      managed with pleural chest tube(s) and suction drainage. Prolonged hospital stay
      and added cost of care are not uncommon. METHODS: Over a 2-year period, 13
      patients with PPP, nonresponsive to conventional management, underwent video
      assisted thoracoscopic surgery (VATS). As part of our protocol for PPP, routine
      preoperative computed tomography of the chest and bronchoscopy to determine the
      presence of associated injuries were performed in all of the patients. During the
      VATS procedure, all of the patients underwent drainage of any retained
      hemothorax, and a topical surgical sealant was applied to the source of the air
      leak as definitive treatment. RESULTS: A persistent pneumothorax with an air leak
      was identified in all 13 of the patients. There were 10 patients with blunt and 3
      patients with penetrating injuries, respectively. The mean age for the patients
      was 34 years (range, 13 to 64 years). Parenchymal lacerations were identified in
      all of the patients ranging in size from 0.5 to 3 cm. After the VATS procedure
      and application of the surgical sealant, 11 patients had the chest tubes removed
      within 24 hours of the procedure. In the other two patients, the chest tubes were
      removed within 48 hours. There was no recurrence of the pneumothorax in any of
      these patients. The mean length of hospital stay before VATS and the application
      of the surgical sealant was 6 days (range, 2-14 days). CONCLUSION: Early VATS and
      the use of a topical sealant in patients with PPP is a safe and effective
      alternative to the conventional management with prolonged thoracostomy chest
      tubes or an open thoracostomy. This alternative management, when used early in
      the appropriate patient, will decrease the length of hospital stay, cost of care,
      and unnecessary procedures.

PMID- 16456445
TI  - LPS-induced acute lung injury is attenuated by phosphodiesterase inhibition:
      effects on proinflammatory mediators, metalloproteinases, NF-kappaB, and ICAM-1
      expression.
AB  - BACKGROUND: Acute endotoxemia is characterized by an enhanced inflammatory
      response. Pentoxifylline (PTX), a phosphodiesterase inhibitor, has been shown to
      decrease TNF-alpha levels and to down-regulate neutrophil activation, likely
      because of increases in intracellular cyclic AMP. Its effects on
      lipopolysaccharide (LPS) induced lung injury, more specifically on tissue
      neutrophil infiltration and degranulation, adhesion molecule expression, and
      transcriptional factor activation, have not been fully investigated. We
      postulated that PTX treatment in acute endotoxemia downregulates the inflammatory
      response and may decrease lung injury. METHODS: Male Sprague-Dawley rats were
      randomized into three groups: Sham (saline i.v.), LPS (5 mg/kg i.v.), and PTX +
      LPS (25 mg/kg and 5 mg/kg i.v., respectively; concomitant injection). After 4
      hours, bronchoalveolar lavage fluid (BAL), plasma, and lungs were sampled. BAL IL
      8 (ELISA), BAL MMP-2, plasma MMP-9, and BAL MMP-9 (Zymography) were measured.
      Lung histology (H&E), in addition to lung MPO, ICAM-1, and NF-kappaB expression
      evaluated by immunohistochemistry were analyzed. Lung NF-kappaB DNA binding was
      evaluated by electrophoretic mobility shift assay. RESULTS: PTX treatment
      decreased BAL IL-8 levels, BAL MMP-2, and plasma MMP-9 activity. Lung neutrophil
      infiltration (MPO), ICAM-1 expression and NF-kappaB activation were decreased by
      PTX. In addition, PTX treatment caused a marked attenuation of LPS-induced lung
      injury. CONCLUSIONS: Phosphodiesterase inhibition by PTX attenuates LPS-induced
      end-organ injury. In addition, proinflammatory cytokine production is also
      downregulated, likely because of the marked attenuation of NF-kappaB DNA binding
      and activation.

PMID- 16456446
TI  - Altered gut flora and environment in patients with severe SIRS.
AB  - BACKGROUND: The gut is considered an important target organ of injury after
      severe insult such as sepsis, trauma, and shock. The impact of bacterial
      translocation or mesenteric lymph on systemic inflammatory response and multiple
      organ damage has been investigated in animals, but dynamic changes in the gut
      flora and environment have not been fully clarified in critically ill patients.
      In the present study, we quantitatively evaluated changes in the gut microflora
      and environment in patients with severe systemic inflammatory response syndrome
      (SIRS). METHODS: Twenty-five patients with severe SIRS, who fulfilled the
      criteria for SIRS, had a serum CRP level >10 mg/dL, and were treated in the
      intensive care unit for more than 2 days, were included in our study. SIRS was a
      result of sepsis in 18 patients, trauma in 6, and burn in 1. A fecal sample was
      used for quantitative evaluation of microflora (bacterial counts of 10 key groups
      including Bifidobacterium and Lactobacillus) by plate or tube technique and of
      the gut environment (pH and 9 organic acids by high speed liquid chromatography).
      Data obtained from patients were compared with corresponding data from healthy
      volunteers. RESULTS: Analysis of fecal flora confirmed that patients with severe
      SIRS had significantly lower total anaerobic bacterial counts (especially 2-4 log
      fewer "beneficial" Bifidobacterium and Lactobacillus) and 2 log higher
      "pathogenic" Staphylococcus and Pseudomonas group counts than those of healthy
      volunteers. Concentrations of total organic acids (especially "beneficial" short
      chain fatty acids such as acetic acid, propionic acid, and butyric acid) in the
      feces were significantly decreased in the patients, whereas pH was markedly
      increased. CONCLUSIONS: The gut flora and environment are significantly altered
      in patients with severe SIRS. Abnormal gut flora and environment may affect
      systemic inflammatory response after severe insult.

PMID- 16456447
TI  - Does the rate of rewarming from profound hypothermic arrest influence the outcome
      in a swine model of lethal hemorrhage?
AB  - BACKGROUND: Rapid induction of profound hypothermic arrest (suspended animation)
      can provide valuable time for the repair of complex injuries and improve
      survival. The optimal rate for re-warming from a state of profound hypothermia is
      unknown. This experiment was designed to test the impact of different warming
      rates on outcome in a swine model of lethal hemorrhage from complex vascular
      injuries. METHODS: Uncontrolled lethal hemorrhage was induced in 40 swine (80-120
      lbs) by creating an iliac artery and vein injury, followed 30 minutes later
      (simulating transport time) by laceration of the descending thoracic aorta.
      Through a thoracotomy approach, a catheter was placed in the aorta and
      hyperkalemic organ preservation solution was infused on cardiopulmonary bypass to
      rapidly (2 degrees C/min) induce profound (10 degrees C) hypothermia. Vascular
      injuries were repaired during 60 minutes of hypothermic arrest. The 4 groups (n =
      10/group) included normothermic controls (NC) where core temperature was
      maintained between 36 to 37 degrees C, and re-warming from profound hypothermia
      at rates of: 0.25 degrees C/min (slow), 0.5 degrees C/min (medium), or 1 degrees
      C/min (fast). Hyperkalemia was reversed during the hypothermic arrest period, and
      blood was infused for resuscitation during re-warming. After discontinuation of
      cardiopulmonary bypass, the animals were recovered and monitored for 6 weeks for
      neurologic deficits, cognitive function (learning new skills), and organ
      dysfunction. Detailed examination of brains was performed at 6 weeks. RESULTS:
      All the normothermic animals died, whereas survival rates for slow, medium and
      fast re-warming from hypothermic arrest were 50, 90, and 30%, respectively (p <
      0.05 slow and medium warming versus normothermic control, p < 0.05 medium versus
      fast re-warming). All the surviving animals were neurologically intact, displayed
      normal learning capacity, and had no long-term organ dysfunction. CONCLUSIONS:
      Rapid induction of hypothermic arrest maintains viability of brain during repair
      of lethal vascular injuries. Long-term survival is influenced by the rate of
      reversal of hypothermia.

PMID- 16456448
TI  - A role for interleukin-10 in the assessment of venous thromboembolism risk in
      injured patients.
AB  - BACKGROUND: Management of patients with multiple trauma requires prophylaxis for
      venous thromboembolism (VTE). This involves recognition of the physiologic
      factors that are associated with VTE risk. Currently, there is no effective
      strategy for risk assessment. The purpose of this study is to investigate the
      relationship of serum P-selectin and interleuken-10 (IL-10) with VTE as a
      possible physiologic marker. METHODS: Patients admitted to two trauma centers
      with an Injury Severity Score >/=9 had blood samples drawn and underwent duplex
      ultrasound scanning of the lower extremities before initiating prophylaxis at
      admission, on days 3 and 7, and weekly until discharge. Patients were prophylaxed
      according to institutional protocols. RESULTS: One hundred eighty-six patients
      were enrolled with a VTE incidence of 17.8%. The population was predominantly
      male (60%), with a mean age of 48 years. sP-selectin levels were not
      statistically different between the groups (64.4 versus 74.8 pg/mL). However, IL
      10 was significantly lower in the VTE group at both the initial and subsequent
      blood draws (21 versus 165 ng/mL, p = 0.012). Further, the ratio of sP-selectin
      to IL-10 (3.92 versus 0.92, p = 0.014) was statistically higher in the VTE group
      at admission. CONCLUSION: An elevated sP-selectin to IL-10 ratio appears to be
      associated with the development of VTE in patients at high risk and may prove to
      be a useful clinical marker for this dreaded complication among trauma patients.
      Early recognition of this high-risk group improves the accuracy of the
      risk/benefit determination for prophylaxis and identifies a group in whom routine
      ultrasound screening would be cost-effective.

PMID- 16456449
TI  - The effect of traumatic brain injury upon the concentration and expression of
      interleukin-1beta and interleukin-10 in the rat.
AB  - BACKGROUND: Using a model of traumatic brain injury (TBI) in the rat, this study
      was undertaken to characterize the short-term biochemical changes of IL-1beta, IL
      10, and tumor necrosis factor TNF-alpha to determine whether injury in the brain
      elicits a systemic cytokine response. METHODS: Sprague-Dawley rats were subjected
      to a TBI using a weight-drop model and then killed at various time points after
      injury. Samples of blood, brain, and liver were recovered and analyzed for
      concentrations of IL-1beta, IL-10, and TNF-alpha as well as IL-1beta and IL-10
      mRNA expression in liver and brain. RESULTS: In brain, IL-1beta increased in the
      first hour after injury, peaked at 8 hours, and declined during the final 16
      hours. IL-10 quickly increased during the first 4 hours and then gradually rose
      over the last 20 hours. Analysis of liver showed no upregulation of these markers
      and plasma IL-1beta and IL-10 were unchanged compared with controls. Although not
      upregulated in brain, TNF-alpha showed a statistically significant (p < 0.05)
      rise in plasma from 14 +/- 16 pg/mL at 20 minutes to 91 +/- 28 pg/mL at 24 hours.
      CONCLUSION: Using a model of TBI, we have demonstrated that there is a rise in
      both IL-1beta and IL-10 in the injured rat brain within the first 24 hours after
      injury without a corresponding rise in either plasma or liver. Therefore, it
      appears as if two strong indicators of brain injury severity are expressed and
      possibly carry out their actions solely in the brain.

PMID- 16456450
TI  - Hemorrhage causes interalveolar perfusion maldistribution in the lungs of
      anesthetized rats.
AB  - BACKGROUND: Lung injury often occurs following hemorrhage and we hypothesized
      that this might be due to the effects of hemorrhage on perfusion distribution
      among alveoli. To test this, we measured interalveolar perfusion distribution in
      anesthetized, spontaneously breathing rats subjected to blood losses of 0%, 10%,
      20%, or 30% of calculated blood volume. METHODS: We measured interalveolar
      perfusion distribution by analyzing trapping patterns of 4-mum diameter
      fluorescent latex particles infused into the pulmonary circulation. The particles
      (2 x 10) were infused 1 hour after each animal had been bled, and the lungs were
      then removed and air-dried. Using a confocal fluorescence microscope, we
      collected images of the particles in eight sections of each lung. Each image
      encompassed 3,360 x 3,360 x 100 microm (approximately 5,000 alveoli), and
      included 3-4,000 particles. Particle distributions in the images were measured
      using the method of dispersion index (DI) analysis. A DI value of zero
      corresponds to a statistically random distribution; the more DI exceeds zero, the
      more the distribution is clustered or inhomogenous. RESULTS: The largest DI
      values for the four groups were: 0%, 0.69 +/- 0.41; 10%, 0.57 +/- 0.58; 20%, 0.72
      +/- 0.34; 30%, 1.38 +/- 0.41. The 30% blood loss group had a max DI value
      approximately twofold greater than those of the other three (p < 0.0001).
      CONCLUSIONS: Our results suggest that interalveolar perfusion distribution
      becomes markedly maldistributed at blood losses of 30%. This contributes to
      ventilation-perfusion mismatching, and may be a precipitating event for lung
      injury following hemorrhage.

PMID- 16456451
TI  - Predictors of the need for nephrectomy after renal trauma.
AB  - BACKGROUND: Initial management of solid organ injuries in hemodynamically stable
      patients is nonoperative. Therefore, early identification of those injuries
      likely to require surgical intervention is key. We sought to identify factors
      predictive of the need for nephrectomy after trauma. METHODS: This is a
      retrospective review of renal injuries admitted over a 12-year period to a Level
      I trauma center. RESULTS: Ninety-seven patients (73% male) sustained a kidney
      injury (mean age, 27 +/- 16; mean Injury Severity Score, 13 +/- 10). Of the 72
      blunt trauma patients, 5 patients (7%) underwent urgent nephrectomy, 3 (4%) had
      repair and/or stenting, and 89% were observed despite a 29% laparotomy rate for
      associated intraabdominal injuries in this group. Twenty-five patients with
      penetrating trauma underwent eight nephrectomies (31%), one partial nephrectomy,
      and two renal repairs. Regardless of the mechanism of injury, patients requiring
      nephrectomy were in shock, had a higher 24-hour transfusion requirement, and were
      more likely to have a high-grade renal laceration (all p < 0.05). Bluntly injured
      patients requiring nephrectomy had more concurrent intraabdominal injuries (p <
      0.0001). Overall, patients after penetrating trauma were more severely injured,
      had higher 24-hour transfusion requirements, and a higher nephrectomy rate (all p
      < 0.05). Despite a higher injury severity in the penetrating group, however,
      mortality was higher in the bluntly injured group (p < 0.0001). Univariate
      predictors for nephrectomy included: revised trauma score, injury severity score,
      Glasgow Coma Scale score, shock on presentation, renal injury grade, and 24-hour
      transfusion requirement. No patient with a mild or moderate renal injury required
      nephrectomy, whereas 6 of 12 (50%) grade 4 injuries and 7 of 8 (88%) grade 5
      injuries required nephrectomy. Multiple logistic regression analysis confirmed
      penetrating injury, renal injury grade, and Glasgow Coma Scale score as
      predictive of nephrectomy. CONCLUSION: Overall, injury severity, severity of
      renal injury grade, hemodynamic instability, and transfusion requirements are
      predictive of nephrectomy after both blunt and penetrating trauma. Nephrectomy is
      more likely after penetrating injury.

PMID- 16456452
TI  - Magnetic resonance imaging in combination with helical computed tomography
      provides a safe and efficient method of cervical spine clearance in the obtunded
      trauma patient.
AB  - BACKGROUND: Assessment of the cervical spine (c-spine) in the obtunded blunt
      trauma patient remains a diagnostic dilemma. In 2002, our institution implemented
      a new c-spine clearance guideline utilizing c-spine computed tomography (CT) and
      magnetic resonance imaging (MRI). This study evaluates the safety and efficacy of
      this guideline. METHODS: Obtunded blunt trauma patients admitted over a 1-year
      period, who underwent both a c-spine CT and a c-spine MRI, were identified.
      Records were reviewed for demographics, mechanism, diagnostic evaluations,
      injuries, and outcome. RESULTS: Fifty-two patients met inclusion criteria. On
      average, patients underwent a c-spine CT on postinjury day 0.4 and MRI on
      postinjury day 4. Forty-four patients had a negative c-spine CT, of whom 13 (30%)
      had a positive MRI for ligamentous injury (p < 0.01). Thirty-one patients had
      both a negative CT and a negative MRI. All patients (n = 8) with positive CTs had
      positive MRIs. The average Injury Severity Score, Abbreviated Injury Score head
      and neck, length of stay, and outcome was not significantly different for
      patients with a c-spine injury. No missed c-spine injuries and no areas of
      cervical collar-related skin breakdown were seen in follow up. CONCLUSIONS: In
      the obtunded patient, expeditious c-spine evaluation is important. Both missed
      injuries and prolonged unnecessary immobilization can result in adverse outcomes.
      This study confirms that c-spine CT, when used in combination with MRI, provides
      a safe and efficient method for c-spine clearance in this patient population. CT
      alone misses a statistically significant number of c-spine injuries.

PMID- 16456453
TI  - The real predictors of disposition in patients with spinal cord injuries.
AB  - OBJECTIVES: A primary goal of health care providers for managing patients with
      spinal cord injury (SCI) is to discharge them to a rehabilitation facility (RF)
      to allow for maximal functional recovery. This study was undertaken to analyze
      hospital mortality and disposition of patients with SCI with a specific focus on
      evaluating the effect of payor source on discharge to a RF. Our hypothesis was
      that commercial insurance (CI) would be the greatest influence of hospital
      disposition. METHODS: All patients under 60 years of age with SCI over a 7-year
      period were identified from the trauma registry; and grouped according to payor
      source: No insurance (NI), Government insurance (GI), No Commercial insurance
      (NCI) (NCI = NI + GI), and CI. RESULTS: A total of 492 patients with SCI were
      identified with a mean age of 33, an ISS of 29, and a hospital mortality of 7.7%.
      Independent predictors of mortality were cervical SCI and blood transfusions.
      Patients who were discharged to a RF had higher ISS and %CI with lower functional
      independent measurement scores compared with patients who were not discharged to
      a RF. Logistic regression analysis demonstrated that the predictors of
      disposition to a RF were CI (p < 0.001) and ISS (p = 0.002). CONCLUSION: The
      presence of CI was an independent predictor of disposition to a RF for patients
      with SCI. Lack of commercial insurance clearly compromises recovery and
      rehabilitation of patients with SCI and predicts outcome more clearly than any
      other parameter. Additional funding for patients without CI is necessary to
      afford all with an equal opportunity for maximal functional recovery.

PMID- 16456454
TI  - The clinical presentation of pediatric thoracolumbar fractures.
AB  - BACKGROUND: The initial evaluation of suspected pediatric thoracolumbar fractures
      can be challenging. We aimed to describe the clinical presentation of
      thoracolumbar fractures in children and adolescents including an evaluation of
      physical examination sensitivity and specificity, and a description of injury
      severity and disposition. METHODS: This was a case control, retrospective study.
      All patients with radiologically proven fractures (January 1997-June 2001) were
      studied. Data were collected in a standardized fashion, as part of the trauma
      registry, and extracted for retrospective analysis, including: patient
      demographics, clinical acuity, mechanism of injury, injury scores, and length of
      stay. RESULTS: There were 96 patients with thoracolumbar fractures (TLF) and 96
      control patients (NTLF) enrolled in our study. The groups were significantly
      different (p < 0.05) regarding several variables including: median age (11 years
      TLF, 7.5 years NTLF), Revised Trauma Score (7.84 for TLF, 7.55 for NTLF), need
      for hospital admission (60% TLF, 86% NTLF), PICD admission (23% TLF, 56% NTLF),
      general surgical procedures (18%TLF, 34% NTLF), Injury Severity Score (8 TLF,
      10NTLF). Patients were not different regarding gender, Glasgow Coma Scale,
      hospital days, or mortality. An abnormal thoracolumbar spine examination was
      noted in 77 TLF patients and 20 NTLF patients, the sensitivity was 87% (95% CI:
      78-93) and the specificity was 75% (95% CI: 65-84). The most common thoracolumbar
      spine abnormality was tenderness. CONCLUSIONS: Thoracolumbar spine fractures are
      more common in older children and adolescents. The physical examination has a
      sensitivity of 87% in this retrospective analysis. Mortality was low and few
      patients required operative intervention for a thoracolumbar fracture.

PMID- 16456455
TI  - Sex differences in creation of do-not-resuscitate orders for critically ill
      elderly patients following emergency surgery.
AB  - BACKGROUND: Emergency surgery patients are older, often critically ill, and at
      high risk of morbidity and mortality. We studied factors associated with issuance
      of a do-not-resuscitate (DNR) order and impact on morbidity and mortality in
      emergency surgery patients. METHODS: Prospective study of all patients since
      January 1, 2000 who underwent emergency surgery before admission to the intensive
      care unit. Data collected were: age, sex, admission diagnosis (case-mix), raw-
      (AIII) and age-adjusted (aAIII) APACHE III scores, issuance of a DNR order, and
      morbidity and mortality. Primary outcomes were DNR status and morbidity and
      mortality. Groups were stratified by age (patients >75 years versus younger) and
      sex. Statistics were calculated by chi(2) test, analysis of variance, and
      logistic regression. RESULTS: In all, 723 emergency surgery patients
      (gastrointestinal: 35%; traumatic: 20%; neurologic: 17%) met study criteria and
      had morbidity and mortality of 17.8% (AIII-predicted: 31%). Ninety-two patients
      (12%) were made DNR, of whom 82.6% died. Women received DNR status more often
      (16.4% versus 9.5%, p < 0.01) but morbidity and mortality was the same for women
      and men (18.2% versus 17.5%, p = 0.85). By logistic regression, sex most
      predicted new DNR status (odds ratio [OR] 2.512, p = 0.005) compared with
      Multiple Organ Dysfunction score (OR 1.410, p < 0.0001), Age (OR 1.054, p <
      0.0001) and aAIII (OR 0.995, 0.355), with goodness of fit of 3.876 (p = 0.868)
      and Nagelkerke R(2) of 0.511. Percent correct was 88.9, implying good
      discrimination. CONCLUSIONS: Female sex and, to a lesser extent, age were
      associated with issuance of DNR in series of patients who received emergency
      surgery. The association of DNR with female sex is an unexpected finding and may
      indicate clinician bias and necessitate the performance of further analysis.

PMID- 16456456
TI  - Halo-vest immobilization increases early morbidity and mortality in elderly
      odontoid fractures.
AB  - BACKGROUND: Odontoid fractures are the most common cervical spine fractures in
      elderly patients. Treatment options included operative fixation (OP) or
      nonoperative management with either a halo-vest (HV) or rigid cervical orthosis
      (CO). Our previous study suggested increased morbidity and mortality with the use
      of HV in the treatment of elderly patients with cervical spine fractures. We
      review a series of odontoid fractures in elderly patients and evaluate for
      predictors for in-hospital morbidity and mortality. METHODS: There were 78
      patients >65 years of age who sustained a type II or III odontoid fracture from
      January 1997 to June 2004 identified from the Rhode Island Hospital Trauma
      registry. Demographic, mechanism, injury pattern, treatment, and outcome data
      were recorded. Patients were analyzed according to treatment method. RESULTS: The
      mean age was 80.7 +/- 0.9 years. There were 50 type II, 17 type III, and 11
      combined fractures. There were 38 (49%) patients treated with HV: 34 with halo
      alone, and 4 after OP; 40 (51%) patients were treated without HV: 27 with CO, and
      13 with OP. There was no difference in injury severity or baseline medical
      condition between HV and non-HV patients. There were 24 (31%) patients who died
      during their hospital stay. Of the HV patients, 42% died compared with 20% in the
      non-HV group (p = 0.03). Major complications occurred in 66% of HV patients
      compared with 36% of non-HV patients (p = 0.003). CONCLUSION: Odontoid fractures
      are associated with significant morbidity and mortality in elderly patients.
      Outcomes after treatment with HV appear inferior to those achieved with CO or OP.

PMID- 16456457
TI  - Endovascular management of a gunshot wound to the thoracic aorta.

PMID- 16456459
TI  - Closed, locked intramedullary nailing of pediatric femoral shaft fractures
      through the tip of the greater trochanter.
AB  - BACKGROUND: Closed femoral nailing is universally accepted as the treatment of
      choice in almost all diaphyseal femoral fractures in adults. Numerous authors
      reported favorable results applying the same surgical technique in the adolescent
      patient group. Nevertheless, reports of complications such as avascular necrosis
      and alteration of the proximal femoral anatomy have dampened the initial
      enthusiasm. The purpose of this paper was to evaluate the possible effect of
      closed intramedullary nailing through the greater trochanter on the proximal
      femoral anatomy. METHODS: We report the results of intramedullary nailing in 20
      skeletally immature patients (13 men and 7 women) with a mean age of 14.4 years
      (range, 11-16 years). All were treated with closed, reamed, percutaneously
      performed nailing, using the tip of the greater trochanter as the nail insertion
      point. The patients were followed for 29 months in average (range, 19-37 months).
      RESULTS: No major complication (limb length discrepancy, avascular necrosis, coxa
      valga) occurred during the observation period. All fractures healed clinically
      and radiographically within 9 weeks in average (8-13 weeks) and all patients
      returned to the preinjury activity level. The mean ATD difference was 1.10 +/-
      3.51 (range, -5-7 mm, 95% CI -0,54/2,74, p = 0.177). The mean LTA distance
      difference was 0.3 mm (range, -6-5 mm, p = 0.158), the mean femoral length
      difference was 1.9 mm (-9-12 mm, p = 0.122) and the overall limb length
      difference was 1.4 mm (-25-20 mm, p = 0.178). The mean neck-shaft angle
      difference was 0.20 +/- 1.74 (range, -3-4, p = 0.612) and the mean neck width was
      0.60 +/- 1.50 (range, -3-3, p = 0.09). Fourteen nails (70%) were removed within
      13 months in average (range, 10-18 months) without any complications. CONCLUSION:
      This study showed that with strict adherence to a surgical technique that
      respects the growing proximal femur and its vascular anatomy, using the tip of
      the greater trochanter as an entry point to the femoral canal, the proven
      advantages of closed, intramedullary nailing can safely be offered to the
      adolescent patient population as well.

PMID- 16456458
TI  - Utility of screening for blunt vascular neck injuries with computed tomographic
      angiography.
AB  - PURPOSE: To prospectively study the impact of implementing a computed tomographic
      angiography (CTA)-based screening protocol on the detected incidence and
      associated morbidity and mortality of blunt vascular neck injury (BVNI). METHODS:
      Consecutive blunt trauma patients admitted to a single tertiary trauma center and
      identified as at risk for BVNI underwent admission CTA using an eight-slice multi
      detector computed tomography scanner. The detected incidence, morbidity, and
      mortality rates of BVNI were compared with those measured before CTA screening. A
      logistic regression model was also applied to further evaluate potential risk
      factors for BVNI. RESULTS: A total of 1,313 blunt trauma patients were evaluated.
      One hundred seventy screening CTAs were performed, of which 33 disclosed
      abnormalities. Twenty-three were evaluated angiographically, of which 15 were
      considered to have significant BVNIs, as were 4 of the 10 patients with abnormal
      CTAs and no angiogram. The incidence of angiographically proven BVNIs in our
      series was 1.1%. If four patients who were treated for BVNIs based on CTA alone
      are included, the incidence rises to 1.4%. This is significantly higher than the
      0.17% incidence before screening (p < 0.001). In addition, the delayed stroke
      rate and injury-specific mortality fell significantly from 67% to 0% (p < 0.001)
      and 38% to 0% (p = 0.002), respectively. Overall mortality also fell
      significantly, from 38% to 10.5% (p = 0.049). Univariate logistic regression
      identified the presence of cervical spine injury as a significant predictor of
      BVNI (p < 0.001). CONCLUSION: CTA screening increases the detected incidence of
      BVNI 8-fold, with rates similar to angiographically based screening protocols.
      CTA screening significantly decreases BVNI-related morbidity and mortality in an
      efficient manner, underlying its utility in the early diagnosis of this injury.

PMID- 16456460
TI  - Blood loss evaluation in children under the age of 11 with femoral shaft
      fractures patients with isolated versus multiple injuries.
AB  - BACKGROUND: Blood loss from non-cavitary hemorrhages is a significant source of
      hypovolemic shock in trauma patients. It has been reported that pediatric femoral
      fractures do not cause excess blood loss if there is no additional injury or
      trauma. The purpose of this study was to define the magnitude of blood loss
      resulting from pediatric femoral fractures and the factors influencing the loss.
      METHODS: Twenty children under the age of 11 with femoral shaft fractures were
      included in this study. The patients' data were collected prospectively for 2
      years. Hemoglobin concentrations, hematocrit levels, emergency room records, and
      clinical findings were evaluated and additional injuries were considered. RESULTS
      AND CONCLUSION: The patients with additional trauma showed significant decreases
      in both hemoglobin concentrations and hematocrit levels, comparison with the
      patients who had only isolated femoral fractures. If there is an obvious decrease
      in hematocrit and/or hemoglobin concentration in a child with a femoral fracture,
      the possibility of additional injuries should be investigated.

PMID- 16456461
TI  - Video-based ergonomic analysis to evaluate thoracostomy tube placement
      techniques.
AB  - BACKGROUND: Thoracostomy for relief of pneumo- or hemothorax may be performed
      emergently at the bedside, in the emergency department or trauma area, often in
      nonideal circumstances. We hypothesized that ergonomic analysis of thoracostomy
      techniques can identify areas for potential improvement in patient and operator
      safety. METHODS: Interviews with Subject Matter Experts (SME) provided steps in
      the task of thoracostomy; 44 thoracostomies (emergent and elective) were video
      recorded and reviewed by SMEs. Ergonomic analyses evaluated surgical performance
      techniques using video clips. RESULTS: Risks to the patient and operator included
      instrument-tray positioning and instrument content. Analyses of video records
      revealed that despite SME-survey consensus, operators inconsistently followed
      recommended techniques. CONCLUSIONS: Discrepancies between SME-recommended and
      observed practice are prevalent, with simple ergonomic problems impeding
      performance, and creating risks for patients and operators. Video-based ergonomic
      analysis is a rich source for identifying task performance problems and potential
      solutions.

PMID- 16456462
TI  - Is contrast enhanced ultrasound an essential tool for liver trauma?

PMID- 16456463
TI  - Military medical surge capacity in times of war and natural disaster.
AB  - BACKGROUND: The military medical services need demand-based strategies to ensure
      the best possible care of the injured in combat and natural disasters without
      compromising peacetime health care commitments at home and abroad. METHODS: A
      review of steps that have already been taken suggests that they are being used to
      their fullest extent commensurate with the public will. In fact, the situation
      has driven preliminary exploration of a special health care personnel draft. We
      believe the answer lies not in expanding the full-time, active duty US medical
      and nursing corps, but rather in tapping identifiable reservoirs of trained
      trauma care physicians, nurses, and allied health care workers in the United
      States and elsewhere. RESULTS: A rudimentary analysis suggests the most promising
      novel considerations are: developing special, trauma-trained reserve units within
      the US civilian trauma care community; seeking temporary attachments of an allied
      country's military medical officers, or a complete medical battalion; and
      contracting with US and foreign trauma surgeons, nurses and allied health
      personnel through a medical private military firm, analogous to those that have
      provided food, housing, transportation, and special combat units in support of
      our major military campaigns and peacekeeping operations. CONCLUSION: These
      considerations have important pros and cons that deserve in-depth evaluation by
      the best military and civilian trauma/critical care and organizational minds
      within a structured organization committed to the needs of military medicine. We
      believe that a Military Medical Think Tank within the Uniformed Services
      University's postgraduate division should be that organization.

PMID- 16456464
TI  - A novel cause of artefact in gunshot trauma imaging.

PMID- 16456465
TI  - Randomized trials in patients with blunt and penetrating trauma.

PMID- 16456467
TI  - Aseptic nonunion of the tibia.

PMID- 16456469
TI  - Elderly trauma inpatients in New York State: 1994-1998.

PMID- 16456472
TI  - July 2005 issue of the Journal of Trauma.

PMID- 16456471
TI  - Workload re-distribution: a new approach to the 80-hour work week.

PMID- 16456476
TI  - X and s charts for health care comparisons.
AB  - In previous articles [M.K. Hart, Qual Manage Health Care. 2004;13(2):99-119 and
      2003;12(1):5-19], the author presented control charts applicable for risk
      adjusted, time-ordered variables and attribute data. The present article uses
      Shewhart X and s charts with risk-adjusted variables data to compare length-of
      stay data from several healthcare organizations. The comparisons are made on the
      data both before and after risk adjustment, enabling the impact of risk
      adjustment to be readily determined.

PMID- 16456477
TI  - Control mechanisms for guideline implementation.
AB  - OBJECTIVES: One approach to reducing health care costs while ensuring high
      quality patient care is the use of medical practice guidelines. This study
      focuses on mechanisms that facilitate the implementation of guidelines primarily
      intended to reduce cost without increasing patient risk, using a
      multiinstitutional case study of a single guideline. SUBJECTS AND METHODS: We
      conducted semistructured interviews with physicians and administrators involved
      with guideline implementation in 61 academic medical centers. The interviews
      included questions on both implementation methods and the final success of
      implementation at each center. RESULTS: We identified 5 factors likely to be of
      importance to the guideline implementation process: (1) the use of a written form
      to routinize the process; (2) the acquisition of informed consent; (3) the
      presence of an active department chair (or section chief) to serve as an opinion
      leader; (4) the use of individual-level monitoring; and (5) the granting of
      financial incentives. CONCLUSIONS: This study allowed the identification of four
      processes for guideline implementation. For hospitals contemplating
      implementation of guidelines aimed toward cost reduction or selective use of
      various agents for other purposes, a decision process to identify the control
      mechanism best suited to an individual institution is a crucial step toward
      success.

PMID- 16456478
TI  - Emergency department performance indicators that encompass the patient journey.
AB  - OBJECTIVE: The study aimed to provide a recommended list of performance
      indicators from routinely collected data that measure most aspects of the patient
      journey through the emergency department (ED). METHODS: Data from a large
      tertiary ED were used to investigate the proposed performance indicators, which
      fell into 7 categories: background information, time from arrival to triage, time
      from triage to treatment, length of stay, readmission rate, left without being
      seen, and deaths in the ED. MAIN RESULTS: Category 1 patients were triaged,
      treated, and discharged rapidly. For category 2 patients, the times from arrival
      to triage increased but times from triage to treatment were relatively stable.
      Patients in categories 3 and 4 were not triaged rapidly and both the arrival to
      triage and triage to treatment processes were unstable and deteriorating. The
      average time to treatment for patients treated outside recommended times was
      unstable and increasing for categories 2, 3, and 4. The number of patients who
      left without being seen was stable except for 2 periods, and the readmission rate
      was stable except for 1 period of increase. CONCLUSION: The performance
      indicators use only routinely collected data and clearly identify the areas in
      which this ED performed poorly.

PMID- 16456479
TI  - Continuing decline in service delivery for family physicians: is the malpractice
      crisis playing a role?
AB  - PURPOSE: This study was conducted to monitor trends in the reduction and
      elimination of services offered by family physicians. In addition, we examined
      whether the malpractice situation may be influencing these trends. METHODS: We
      surveyed all family physicians in rural Florida and an equal number of randomly
      selected, urban, family physicians in the state. We examined changes in
      professional liability insurance (PLI) premiums, and changes in services offered,
      practice satisfaction, and future practice plans. RESULTS: Overall, 308 (42.1%)
      family physicians responded. Results suggest that 60.3% of them reduced or
      eliminated services in the last year. Specifically, almost two thirds of
      respondents had eliminated hospital-based surgeries (65.2%) and vaginal
      deliveries (64.5%). Furthermore, endoscopies were decreased or eliminated by 69%
      of survey participants, and coverage of emergency departments and nursing homes
      was reduced or eliminated by 64.1% and 56.4% of respondents, respectively.
      Increases in the PLI averaged 78.2%. Overall increases in the PLI were
      significantly related to a decrease or elimination of services offered by family
      physicians. Dissatisfaction with practice was relatively high (36.8%) and was
      associated with both the reduction of services and an intention to leave practice
      within 2 years. No major differences in these trends were noted between rural and
      urban family physicians. CONCLUSIONS: Access to care provided by rural and urban
      family physicians in Florida is being hampered by the malpractice situation and
      other factors. Policymakers may need to focus on these factors in an effort to
      relieve additional barriers to care for vulnerable populations.

PMID- 16456480
TI  - Knowledge-based quality management and clinical pathways.
AB  - OBJECTIVES: Although 65% of the hospitals in Taiwan claim to be applying the
      clinical pathway concept, most hospitals do not implement this concept
      effectively. The purpose of this study was to determine the reasons for the
      improper or inappropriate application of the clinical pathway design in
      hospitals. METHODS: This study differs from other studies in clinical pathway
      design and application in that it seeks to resolve misunderstandings of the
      clinical pathway analysis that may have been generated by the responses to survey
      questionnaires. Therefore, in-depth interviews and Senge's system archetype have
      been used to ascertain the reasons why the use of a clinical pathway design has
      been ineffective. We also used the 4 dimensions of knowledge-based management
      proposed by Drucker to set up the knowledge-based clinical pathway. Thirteen
      experts used the Delphi method to construct 20 knowledge-based clinical pathway
      guidelines. CONCLUSIONS: The application of knowledge- and management-based
      clinical pathway designs is recommended.

PMID- 16456481
TI  - The need for quality management in primary health care in Cyprus: results from a
      medical audit for patients with type 2 diabetes mellitus.
AB  - OBJECTIVES: To assess the quality of clinical management regarding metabolic and
      blood pressure control in a cohort of patients with type 2 diabetes in the
      primary health care setting of Cyprus. SUBJECTS AND METHODS: Medical care,
      received by 296 patients with type 2 diabetes from 4 primary care health centers
      in Cyprus, was assessed for 1 year. Data were collected retrospectively using
      chart review and a telephone survey. Most recent values of HbA1c, fasting blood
      glucose, blood pressure, and lipid values were used to assess attainment to
      internationally accepted treatment targets. RESULTS: Mean age was 70 years, 75%
      of patients being older than 65. Average diabetes duration was 13 years. Almost
      90% of patients had visited a general practitioner during 1 year, on average 8.3
      times. Hypertension and hyperlipidemia were present in 67% and 32% of patients,
      respectively. Overall, diabetes care provided by the 4 primary care health
      centers appeared to be suboptimal with regard to frequency of metabolic and blood
      pressure measurements as well as targets reached. Only 10.5% of all patients had
      at least 1 HbA1c value recorded, and 77.4% of them had HbA1c levels of 8% or
      more. Of the patients who had a low-density lipoprotein cholesterol measurement
      during the examined year (29.4%), only 20.7% had a value less than 100 mg/dL.
      Only 34.5% of patients used lipid-lowering agents, and only 15.9% were receiving
      aspirin. CONCLUSION: Our findings suggest that the management of type 2 diabetes
      is suboptimal in the primary health care setting of Cyprus. A multifaceted
      intervention, already in progress in 2 health centers, is expected to improve the
      quality of diabetes care.

PMID- 16456485
TI  - Safety and efficacy of growth hormone therapy in childhood.
AB  - Growth hormone (GH) has been used for more than 40 years. GH improves height
      velocity in many conditions associated with impaired growth and corrects
      metabolic deficits attributable to GH deficiency (GHD). Many studies and
      surveillance programs exist to collect efficacy and safety data. GH has been
      demonstrated to have a relatively wide safety margin. Reported side effects,
      including pseudotumor cerebri, edema, slipped capital femoral epiphysis (SCFE),
      worsening of scoliosis, gynecomastia, and hyperglycemia require careful
      monitoring. Currently, there are no data suggesting that GH therapy increases the
      risk of developing de novo, recurrent, or secondary malignancies. Patients who
      have a high intrinsic risk factor for the development of an adverse event need
      more vigilant surveillance.

PMID- 16456486
TI  - Insulin-like growth factor-I (lGF-l): safety and efficacy.
AB  - Insulin-like growth factor I (IGF-I) is a peptide synthesized mainly in the liver
      by stimulation by pituitary growth hormone (GH). It circulates almost entirely
      bound to its binding proteins. It is the anabolic effector hormone of GH. It is
      the only treatment in states of GH resistance such as Laron syndrome and blocking
      antibodies to human GH. As it suppresses insulin and GH secretion it has been
      used in states of insulin resistance including Type II diabetes mellitus. IGF-I
      is administered by once or twice daily injections. Adverse effects are mostly
      caused by overdosage. The usual daily dose in children ranges from 100-200
      microg/kg.

PMID- 16456487
TI  - GHRH and GH secretagogues: clinical perspectives and safety.
AB  - The diagnosis and treatment of growth hormone deficiency (GHD), as well as the
      possibility of counteracting somatopause and age-related changes in body
      composition, structural functions, and metabolism, prompted interest in potential
      clinical uses of GH-releasing hormone (GHRH) and GH secretagogues (GHS). GHD
      often reflects hypothalamic GHRH deficiency and it has been clearly demonstrated
      that the age-related decline in the function of the GH/IGF-I axis reflects a
      reduction in hypothalamic function as evidenced by the preservation of the
      releasable pool of pituitary GH in aged subjects. The effectiveness of
      recombinant human GH (rhGH) is well established, but it is also recognized that
      GH replacement does not mimic physiological GH secretion which theoretically
      would be restored by GHRH and/or GHS. At present, it has been clearly
      demonstrated that GHRH and/or GHS represent reliable tools for the diagnosis of
      GHD. On the other hand, neither GHRH nor GHS has been shown to provide effective
      alternatives to rhGH for the treatment of GHD. Although GHRH and/or GHS represent
      the most logical approaches for the restoration of the GH/IGF-I axis to a
      youthful level of activity and for counteracting the somatopause, this hypothesis
      has never been proven definitively. Conceptually, GHRH replacement would be the
      most physiological approach and its safety is guaranteed, provided an appropriate
      dose is used, in order to avoid hyperactivity of the GH/IGF-I axis. However, a
      long-acting preparation is needed. On the other hand, GHS, e.g., ghrelin
      analogues, could be considered as a function of their selectivity of action.
      However, ghrelin has a wide spectrum of endocrine and non-endocrine actions at
      both central and peripheral levels. Thus, non-selective GHS, although available
      in orally active forms, could elicit unforeseen side effects. Previous studies
      with GHRH and/or GHS in aging patients provided encouraging results. However, it
      still remains to be definitively demonstrated that aged subjects would benefit
      from chronic treatment with these molecules.

PMID- 16456488
TI  - Drugs and hormones used to treat pediatric and adolescent reproductive endocrine
      disorders.
AB  - Pediatric and adolescent reproductive endocrine disorders represent a myriad of
      diseases including cryptorchidism, male and female sex steroid deficiencies,
      precocious puberty, and polycystic ovarian syndrome. While there are many
      traditional therapeutic interventions, some disorders now benefit from new
      medications or formulations. In this article, we review the most commonly used
      pharmacological therapies for these disorders and discuss treatment controversies
      and toxicities.

PMID- 16456489
TI  - Prolactin excess: treatment and toxicity.
AB  - Dopamine agonists provide highly effective therapy for the treatment of
      hyperprolactinemia. As a result of their efficacy and tolerability, these agents
      are considered to be the initial therapy of choice in children, adolescents and
      adults with idiopathic hyperprolactinemia and prolactinomas. The four dopamine
      agonists, bromocriptine, pergolide, cabergoline and quinagolide, share a similar
      mechanism of action and side effect profile. Although studies of cabergoline have
      demonstrated the highest treatment efficacy and tolerability, all four of these
      agents are safe, effective and tolerable in children and adolescents. When
      fertility is desired, bromocriptine is generally preferable, but cabergoline is
      also likely safe; pergolide and quinagolide should not be used in this setting.

PMID- 16456490
TI  - Vasopressin and desmopressin in central diabetes insipidus: adverse effects and
      clinical considerations.
AB  - The management of central diabetes insipidus has been greatly simplified by the
      introduction of desmopressin (DDAVP). Its ease of administration, safety and
      tolerability make DDAVP the first line agent for outpatient treatment of central
      diabetes insipidus. The major complication of DDAVP therapy is water intoxication
      and hyponatremia. The risk of hyponatremia can be reduced by careful dose
      titration when initiating therapy and by close monitoring of serum osmolality
      when DDAVP is used with other medications affecting water balance. Herein we
      review the adverse effects of DDAVP and its predecessor, vasopressin, as well as
      discuss important clinical considerations when using these agents to treat
      central diabetes insipidus.

PMID- 16456491
TI  - Safety of medications and hormones used in the treatment of pediatric thyroid
      disorders.
AB  - Levo-thyroxine (L-T4) is used to treat children with any form of hypothyroidism.
      In fact, L-T4 is the natural hormone and the principal product secreted by the
      thyroid. It is then converted into T3, the active compound at the tissue level,
      according to the temporary needs of the organism. Therefore, L-T4 can replace
      thyroid function in hypothyroid patients on a physiological basis. L-T4
      administration is a safe and beneficial treatment that can be easily monitored by
      the concomitant measurement of TSH and free thyroid hormone levels. Antithyroid
      drugs (methimazole [MMI], carbimazole [CMI] and propylthiouracil [PTU]) are the
      initial treatment of choice for most children with hyperthyroidism, which is most
      commonly caused by Graves' disease. While generally similar in efficacy and
      safety, there are some differences. MMI and CMI have a longer half-life and so
      can be given once daily, improving compliance in children. At low doses, there
      are fewer side effects with MMI and CMI compared to PTU. Drug-related hepatitis
      and vasculitis are almost exclusively seen with PTU. Beta-adrenergic antagonists
      are safe adjunctive therapy. In specific situations, e.g., in preparing for
      thyroid surgery, iodine for a limited time is used to inhibit thyroid hormone
      secretion and reduce gland vascularity.

PMID- 16456492
TI  - Safety of medications and hormones used in pediatric endocrinology: adrenal.
AB  - Glucocorticoids have been prescribed for several decades in treating adrenal
      insufficiency of various etiologies. These drugs are also heavily used in
      treating non-endocrine disease. This article will focus on adverse side effects
      encountered in the chronic use of different types of glucocorticoids in children
      and young adults with endocrine causes of adrenal insufficiency. Dosing
      guidelines are discussed with a view toward minimizing the common co-morbidities
      of growth suppression, excess weight gain, and osteopenia, among others. This
      article also discusses the use of several inhibitors of adrenal steroid
      biosynthesis and one glucocorticoid receptor antagonist for the medical treatment
      of Cushing syndrome.

PMID- 16456493
TI  - Adverse effects of hormone preparations and related medications used to treat
      disorders of bone and mineral metabolism.
AB  - Disorders of bone and mineral metabolism can be effectively treated by a
      relatively small number of preparations which include minerals, vitamin D
      metabolites, other hormones, bisphosphonates, and diuretics. In addition to
      achieving the treatment goals, management of these patients must include close
      monitoring for potential adverse effects of the medications. The following
      chapter addresses the currently available treatment modalities of bone and
      mineral disorders and their potential side effects. Careful attention to
      recommended precautions, means of monitoring for potential adverse effects, and
      consequent adjustment of therapy play a key role in protecting the patient from
      development of serious adverse effects.

PMID- 16456494
TI  - Insulins and oral hypoglycemic medications.
AB  - The management of childhood diabetes is rapidly evolving, reflecting both the
      recognition of new types of diabetes in pediatrics and the availability of new
      insulins. Over the past two decades there have been increasing numbers of
      children affected by type 2 diabetes, maturity onset diabetes of youth (MODY),
      and medical diabetes secondary to medication usage (e.g. prednisone) or disease
      process (e.g., cystic fibrosis). These forms of diabetes require familiarity with
      medications other than insulin and an understanding of appropriate treatment
      strategies. Simultaneously, after years of little change, there has been the
      relatively rapid introduction of new insulins (e.g., lispro, aspart, glargine)
      and more sophisticated means of insulin delivery (e.g., pumps, pens, inhalers).
      Taken as a whole, these trends present a challenge to the pediatric diabetes
      specialist. In this article, the medications that are now frequently used in
      diabetes treatment are reviewed, including the indications for use, the usual
      dose, dose adjustment strategies, common side effects and anticipated outcomes.
      The diabetes literature on the new insulins and diabetes medications is reviewed,
      with an emphasis on the limited pediatric data. The goal is to familiarize the
      practicing pediatric diabetes specialist with these medications and their usage.

PMID- 16456495
TI  - Medications used in the treatment of hypoglycemia due to congenital
      hyperinsulinism of infancy (HI).
AB  - Congenital hyperinsulinism of infancy is the commonest cause of persistent and
      recurrent hypoglycaemia in the neonatal and infancy period. It is a heterogeneous
      disorder with respect to clinical presentation, histology, molecular biology and
      genetics. The biochemical profile is one of hypoketotic, hypofattyacidemic
      hypoglycemia. To prevent permanent brain damage from hypoglycemia, the treatment
      of infants with congenital hyperinsulinism must be prompt and aggressive. The
      drugs used in the medical therapy for congenital hyperinsulinism are diazoxide,
      octreotide, glucagon and nifedipine.

PMID- 16456496
TI  - Anti-obesity medication use in adolescents: risks and benefits.
AB  - Pharmacological agents currently used to treat obese adolescents decrease
      appetite or reduce fat absorption from the gastrointestinal tract. This paper
      summarizes the indications for pharmacotherapy and the potential benefits and
      risks of anti-obesity medications.

PMID- 16456497
TI  - Lipid-lowering medications.
AB  - In the last decades, there has been an important progression in the development
      and assessment of various cholesterol-lowering agents. Until recently, in
      children under age 10, the focus of treatment has been on dietary and lifestyle
      adjustments. For children older than 10 years, bile acid-binding resins were also
      recommended if LDL-C levels remained high after dietary adjustment. However, the
      lipid-lowering effect of bile acid-binding resins is modest at best and long-term
      compliance is often poor. In contrast, HMG-CoA reductase inhibitors (statins) are
      currently widely used in adults and are considered the first choice in the
      treatment of hypercholesterolemia. In the last few years, several randomized
      trials have shown that statins are also effective in reducing LDL cholesterol
      levels in children and seem safe at least in the short term. Another novel
      development is the cholesterol-lowering agent, ezetimibe, which inhibits
      cholesterol absorption in the intestine. Although efficacy and safety data in
      children are still lacking, ezetimibe has a good safety profile in adults, either
      as monotherapy or in combination with a statin. Lastly, two other classes of
      lipid-lowering drugs include fibrates and nicotinic acid, but most agree that the
      side effect profile precludes their use in children except in extreme
      circumstances. Overall, therapeutic options to lower cholesterol levels in
      children are expanding.

PMID- 16456499
TI  - An overview of the GHMonitor, a registry of children treated with Saizen
      somatropin [recombinant hGH for injection].
AB  - The GHMonitor, introduced in 1998, monitors demographics and outcomes in children
      treated with Saizen (somatropin [recombinant hGH for injection]). Follow-up data
      are available on 697 patients. The proportion of male to female patients
      receiving growth hormone (GH) treatment was 67:33. Severity of the height deficit
      present at enrollment varied by diagnosis with patients with Turner syndrome
      being shortest [height standard deviation score (SDS)=-3.7+/-1.7] and those with
      organic GH deficiency the least severely stunted (height SDS=-1.9+/-1.5). Forty
      eight patients (6.9%) discontinued participation in the registry. The most common
      reason for discontinuing GH was completion of growth; the second was family
      relocation. There were 53 adverse events reported in 33 patients in 1977 patient
      years of followup. Most were self-limited but 13 were serious, and 5 resulted in
      discontinuation of treatment. Data from The GHMonitor provide a real world
      glimpse of current North American GH treatment practices.

PMID- 16456500
TI  - Patient outcomes in the GHMonitor: the effect of delivery device on compliance
      and growth.
AB  - To determine the effect of method of growth hormone (GH) administration on
      patient outcomes, we studied data from the GHMonitor, an electronic database
      registry of North American children treated with Saizen GH (somatropin [rDNA
      origin] for injection). Data from 631 children, 305 treated with needle and
      syringe and 326 treated with cool.click needle-free device, were analyzed. The
      groups were balanced for factors known to affect GH treatment response. There was
      no difference in response to GH over 2 years of treatment whether assessed by
      growth rate, change in height SD score, or change in height age. Although the
      majority of patients were compliant with GH therapy (84.6% of needle-free
      delivery system [NFDS] and 76.3% of needle and syringe patients missed <3 doses
      per month), significantly more patients using needle and syringe missed over one
      half of their prescribed GH dose (13.4% needle and syringe patients versus 6% of
      NFDS patients, P=.002). In this group of poorly compliant patients, growth rates
      were significantly lower than in patients who missed fewer doses. Thus in
      patients where compliance is an issue, use of the NFDS may result in better
      outcomes.

PMID- 16456501
TI  - Assessing bone health in children: who to test and what does it mean?
AB  - The foundation of bone health is established during childhood and adolescence.
      Unfortunately, pediatric bone health may be threatened in a variety of genetic
      and acquired disorders. Low bone mineral density (BMD) and/or fragility fractures
      may result. This paper addresses the pediatric indications for bone densitometry
      testing in children at risk for poor bone health and the challenges of
      interpreting the results. Dual energy x-ray absorptiometry (DXA) is the most
      commonly used of the bone densitometry methods. Most DXA software programs report
      BMD in terms of a T-score, which compares the results to adult norms. Z-scores,
      based upon age- and gender-matched reference data, should be used instead to
      avoid the mislabeling of a child as "osteoporotic." Delayed growth and maturation
      also complicate the interpretation of DXA findings in chronically ill patients.
      Although children with low BMD values may have an increased risk of fracture, a
      pediatric "fracture threshold" has not been established. Further research is
      needed to refine the indications for bone density testing in children and to aid
      in the interpreting the results.

PMID- 16456502
TI  - Pediatric DXA bone measurements.
AB  - Dual-energy x-ray absorptiometry (DXA) has become the most commonly employed
      technique worldwide for assessment of bone mineral content in adults and
      children. DXA interpretation in children is more complex because bone dimensions
      are highly dynamic. Pediatric use of DXA can be used to identify risk of adult
      osteoporosis. This technology and the increasing knowledge of the genetics,
      mutations, and mutagens associated with the development of osteoporosis are tools
      to identify the phenotypes and genotypes in children at risk for osteoporosis
      later in life, and to design appropriate early interventions for this condition.
      This paper gives a brief overview of how DXA works, calibration issues, efficacy,
      safety, and test interpretation.

PMID- 16456503
TI  - Renal phosphate--wasting disorders in childhood.
AB  - The purpose of this review paper is to provide a summary of recent developments
      in the childhood disorders of renal phosphate-wasting, with particular emphasis
      on two of the hereditary conditions, X-linked hypophosphatemia (XLH) and
      autosomal dominant hypophosphatemic rickets (ADHR), as they are distinguished
      from the paraneoplastic syndrome, oncogenic hypophosphatemic osteomalacia (OHO).
      An overview of the clinical manifestations, pathogenesis, diagnosis, and
      treatment of these conditions, with attention to newly-discovered genetic and
      hormonal signatures, will be discussed. The information may be invaluable in the
      complex diagnosis and successful treatment of OHO and hereditary
      hypophosphatemias of childhood.

PMID- 16456504
TI  - Genetic and genomic approaches to studying stature and pubertal timing.
AB  - Stature and puberal timing are two complex genetic traits that vary widely within
      a population due to a combination of genetic and environmental factors. Rare
      mutations explain a fraction of severe short stature, but rare mutations are less
      likely to explain most of idiopathic short stature or most of the population
      variation in height or the timing of puberty. In this review, we discuss how
      association and linkage studies, in conjunction with new genomic technologies,
      will allow researchers to survey genes for the variants that underlie these
      traits. For both association and linkage studies to be successful, large samples
      and careful interpretation are critical.

PMID- 16456505
TI  - Is congenital growth hormone deficiency ever transient?
AB  - Both growth hormone (GH) and glucocorticoids are important in regulating blood
      glucose levels. In addition to their direct effects on intermediary metabolism
      and on blood glucose, glucocorticoids have an important role in normal GH
      synthesis and release. They modulate somatostatinergic tone and GH releasing
      hormone (GHRH) receptor synthesis. Additionally, they have direct effects on GH
      messenger (mRNA) synthesis and stabilization. This paper will discuss the
      evidence supporting these interactions and how they apply clinically to
      diagnosing the cause of hypoglycemia in a newborn infant.

PMID- 16456506
TI  - [MRI-intracranial compliance analysis in patients with NPH].
AB  - We devised a method for non-invasively assessing intracranial compliance with
      retrospective ECG-triggered phase contrast cine MRI. This method was examined in
      patients with normal pressure hydrocephalus (NPH) group and those with
      asymptomatic ventricular dilation or brain atrophy (VD group), and in healthy
      volunteers (control group). Intracranial volume change (DeltaV(max)) was
      calculated from arterial inflow, venous outflow, cerebrospinal fluid (CSF) flow,
      and spinal cord motion at the C2 level during a cardiac cycle. Next, craniospinal
      CSF pressure gradient change (DeltaPG(max)) was calculated from measured CSF flow
      velocity using a simplified Navier-Stokes equation. Finally, Ci was obtained by
      dividing Delta V(max) into DeltaPG(max). Ci in the NPH group was significantly
      smaller and could be differentiated from other groups. This method makes it
      possible to non-invasively obtain a more detailed determination of the
      intracranial state and dynamics in NPH and to assist in its diagnosis.

PMID- 16456508
TI  - [Optimization of basic adjustable data-acquisition parameters for continuous
      three-dimensional whole-body FDG-PET].
AB  - The SET-3000 G/X (Shimadzu Corp., Kyoto, Japan) has a large aperture and
      functions as a three-dimensional (3D) dedicated PET scanner. However, the large
      number of line of responses in the SET-3000 G/X scanner creates a large volume of
      sinogram data and prolongs reconstruction time in iterative reconstruction. The
      purpose of this study was to optimize basic acquisition parameters (maximum ring
      difference and span) for sensitivity and spatial resolution for 3D whole-body
      (18)F-FDG PET. METHODS: Detector rings and image planes numbered 50 and 99,
      respectively. In sensitivity measurement, the maximum ring difference (MRD) was
      changed from 1 to 49. In the measurement of spatial resolution, the span was
      changed from 3 to 21. For sensitivity and spatial resolution measurements, the
      standard protocols defined by the Japan Radioisotope Association (JRIA) 1994 and
      the National Electrical Manufacturers Association (NEMA) NU 2-2001 were used. We
      also evaluated the corresponding image noise by placing identical ROI on the
      reconstructed images. RESULTS: The total sensitivity of MRD=49 was 85.7 cps/Bq/ml
      in a uniform phantom (15 cm diameter, 30 cm tall cylinder) filled with (18)F.
      This was approximately two times higher than MRD=13. The image noise in the
      center of the axial FOV decreased with increasing MRD. Spatial resolution was
      slightly decreased as MRD increased, but axial resolution deteriorated with a
      span of more than 11. CONCLUSION: Optimum basic data-acquisition parameters for
      whole-body (18)F-FDG PET were MRD 49 to obtain maximum sensitivity and span 9 to
      avoid decreasing spatial resolution. Additionally, it was concluded that the
      basic data-acquisition parameters should be carefully selected for 3D whole-body
      (18)F-FDG PET in order to maximize the efficiency of PET measurement.

PMID- 16456507
TI  - [Usefulness of attenuation correction with transmission source in myocardial
      SPECT].
AB  - Attenuation correction in SPECT has been used for uniformly absorptive objects
      like the head. On the other hand, it has seldom been applied to nonuniform
      absorptive objects like the heart and surrounding lungs because of the difficulty
      and inaccuracy of data processing. However, since attenuation correction using a
      transmission source recently became practical, we were able to apply this method
      to a nonuniform absorptive object. Therefore, we evaluated the usefulness of this
      attenuation correction system with a transmission source in myocardial SPECT. The
      dose linearity, defect/normal ratio using a myocardial phantom, and myocardial
      count distribution in clinical cases was examined with and without the
      attenuation correction system. We found that all data processed with attenuation
      correction were better than those without attenuation correction. For example, in
      myocardial count distribution, while there was a difference between men and women
      without attenuation correction, which was considered to be caused by differences
      in body shape, after processing with attenuation correction, myocardial count
      distribution was almost the same in all cases. In conclusion, these results
      suggested that attenuation correction with a transmission source was useful in
      myocardial SPECT.

PMID- 16456509
TI  - [Survey and analysis of radiation safety management systems at medical
      institutions--second report: radiation measurement, calibration of radiation
      survey meters, and periodic check of installations, equipment, and protection
      instruments].
AB  - We carried out a questionnaire survey to determine the actual situation of
      radiation safety management measures in all medical institutions in Japan that
      had nuclear medicine facilities. The questionnaire consisted of questions
      concerning the evaluation of shielding capacity; radiation measurement; periodic
      checks of installations, equipment, and protection instruments; and the
      calibration of radiation survey meters. The analysis was undertaken according to
      region, type of establishment, and number of beds. The overall response rate was
      60 percent. For the evaluation of shielding capacity, the outsourcing rate was 53
      percent of the total. For the radiation measurements of "leakage radiation dose
      and radioactive contamination" and "contamination of radioactive substances in
      the air," the outsourcing rates were 28 percent and 35 percent of the total,
      respectively (p<0.001, according to region and establishment). For the periodic
      check of radiation protection instruments, the implementation rate was 98
      percent, and the outsourcing rate was 32 percent for radiation survey meters and
      47 percent for lead aprons. The non-implemented rate for calibration of radiation
      survey meters was 25 percent of the total (p<0.001, according to region and
      establishment). The outsourcing rate for calibration of radiation survey meters
      accounted for 87 percent of the total, and of these medical institutions, 72
      percent undertook annual calibration. The implementation rate for patient
      exposure measurement was 20 percent of the total (p<0.001, according to number of
      beds), and of these medical institutions 46 percent recorded measurement outcome.

PMID- 16456510
TI  - Simulator-assisted setting of scan protocols for X-ray CT: development and
      clinical usefulness of the Scan Plan Simulator.
AB  - To assist in the selection of complicated computed tomography (CT) scan protocols
      and to obtain stable image SD values, prototype "Scan Plan Simulator" software
      with the following functions was developed and evaluated. 1) The image SD value
      that will be obtained in actual scanning is estimated by entering the patient's
      body size and scan protocol, after which a simulated image is displayed so that
      the estimated image SD value can be checked. The exposure dose can also be
      estimated in the Scan Plan Simulator. 2) The appropriate tube current is
      automatically set by entering the required image SD value. We evaluated the
      accuracy of the Scan Plan Simulator by comparing the simulation results with the
      image SD values and exposure dose obtained in actual scanning and assessed the
      usefulness of this method using Monte Carlo simulation based on body thickness
      data obtained in clinical examinations. The results showed that the Scan Plan
      Simulator not only stabilizes image SD by minimizing the effects of body size but
      also permits the exposure dose to be reduced by optimizing tube current.

PMID- 16456511
TI  - [Study of the extended process for mammographic film with two-dimensional shape
      analysis of micro-calcifications].
AB  - This paper describes the extended development process (extended process) that
      compensates for the image quality of mammographic film exposed at a lower
      radiation dose. First, we developed films exposed to a phantom with several small
      particles that simulated micro-calcifications at high and lower radiation doses,
      respectively. Next, we evaluated the image quality of those films developed for
      the standard development time of 90 seconds, and for the extended development
      times of 150 seconds and 210 seconds. Then we extracted micro-calcification
      regions and calculated the areas, perimeters, and normalized areas of micro
      calcifications by using image analysis. There was no significant difference in
      areas or shape measurements between the development times of 90 seconds and 150
      seconds in obtaining the same high-quality images as the standard process.
      Therefore, we determined that the development time of 150 seconds was the most
      appropriate time. As a result, we achieved a 20% reduction in radiation dose by
      using the extended process for mammographic film.

PMID- 16456512
TI  - Computational flow dynamics in abdominal aortic aneurysm using multislice
      computed tomography.
AB  - Following the introduction of a new multislice computed tomography (MSCT)
      scanner, it has become possible to produce high-speed CT angiography (CTA), the
      preferred method for imaging in emergent abdominal vascular conditions. Unlike
      catheter angiography, multislice CTA not only depicts the vessels but also allows
      perfusion in adjacent organs to be assessed. To make the most effective
      diagnostic use of multi-detector row CTA and three-dimensional image post
      processing, radiologists must be familiar with the optimal CTA protocols and the
      typical CT findings in various emergent vascular conditions using computational
      flow dynamics (CFD). This article describes a technical approach to estimating
      the blood flow state of human abdominal aortic aneurysms (AAA) in more detail by
      constructing realistic three-dimensional (3D) vessel models using CFD methods,
      focusing on pre- and postoperative cases.

PMID- 16456513
TI  - [Evaluation of change in the optimal image reconstruction phase in retrospective
      ECG-gated reconstruction].
AB  - The purpose of this study was to optimize the reconstruction phase in order to
      improve depiction of the coronary artery in the relative delay method of the
      retrospective electrocardiogram (ECG)-gated reconstruction technique using a
      multi-slice computed tomography (MSCT) scanner with four channels. The following
      items were evaluated; 1) image quality of the coronary arteriogram, 2) degree of
      difference between the standard phase corresponding to the diastasis period and
      the selected phase, which was determined in each case to obtain the best image,
      and 3) the factors causing the phase difference. The image quality in the
      selected phase was better than that in the standard phase. A positive correlation
      was observed between the degree of phase difference and the median value and
      standard deviation of the heart rate. The degradation of image quality was
      remarkable in cases showing a large degree of phase difference. A negative
      correlation was observed between image quality in the selected phase and the
      degree of phase difference. Individualizing the reconstruction phase is required
      to improve the image quality of coronary arteriograms with MSCT. It should be
      noted that the condition of a low and stable heart rate results in reduction in
      the degree of phase difference, which is useful for the acquisition of better
      images.

PMID- 16456514
TI  - [Evaluation of setup error and adequate setup margins in patients with prostate
      cancer treated by IMRT and fixed in the prone position using a set of
      immobilization devices].
AB  - PURPOSE: Positional reproducibility in patients with prostate cancer fixed in the
      prone position with a set of immobilization devices for external-beam intensity
      modulated radiation therapy (IMRT) was evaluated. In addition, the adequacy of
      our positional error reduction strategy and current planning target volume (PTV)
      margins was also evaluated. RESULTS: Systematic error was corrected by the
      positional correction that we executed at the first stage of irradiation. The
      setup margin that we had calculated was 1.1 mm in the L-R direction, 1.3 mm in
      the A-P direction, and 2.7 mm in the C-C direction. CONCLUSION: We determined
      that the effectiveness of the method of correcting the error margin and the setup
      accuracy of the fixed method were well maintained.

PMID- 16456515
TI  - [Basic experimental study of intraosseous venography using carbon dioxide
      contrast agent in percutaneous vertebroplasty].
AB  - PURPOSE: In percutaneous vertebroplasty (PVP), intraosseous venography is
      performed using water-soluble ionic iodinated contrast media (iodine contrast
      media) before injecting bone cement. However, because of contrast medium
      remaining in the fractured cleft, we experienced the persistence of
      intravertebral opacification that obscured visualization of the cement under X
      ray fluoroscopy. To solve this problem, we examined carbon dioxide (CO(2)) as a
      contrast medium. METHODS: We measured the contrast of iodine contrast media and
      CO(2) and performed a subjective assessment of imaging by enforcing intraosseous
      venography by changing the tube voltage and image intensifier (I.I.) entrance
      dose in a bone sample of a cadaver using iodine contrast media and CO(2). In vivo
      study, we performed a subjective assessment of images obtained by intraosseous
      venography using CO(2) under two kinds of X-ray views. RESULTS: We determined
      that the contrast of CO(2) is 1/6-1/7.5 that of iodine contrast media, and that
      CO(2) fluctuates less in its contrast value with changes in tube voltage. In our
      assessment of the image of the bone sample, CO(2) performed worse that iodine
      contrast media. However, if the I.I. entrance dose is kept above 2.5 microGy/F,
      CO(2) is considered to be of clinical use. In the clinical image assessment, the
      best conditions were an image collection rate of 7.5 F/S and matrix of 1024 x
      1024. CONCLUSIONS: CO(2) did not cause any obstacles when we injected bone
      cement, and its I.I. entrance dose, image collection rate, and matrix size
      indicate that it can be used for intraosseous venography.

PMID- 16456516
TI  - [Problems of SNR evaluation method in parallel MRI].

PMID- 16456517
TI  - Influence of knee pathology on body posture and muscle activity of head, neck and
      trunk muscles.
AB  - AIM: The aim of the study was to evaluate the effects that an anterior cruciate
      ligament (ACL) injury of the knee has on postural control and activity of neck,
      head and trunk muscles in order to investigate the existence of connections
      between the masticatory system and body posture. METHODS: Surface
      electromyographic (sEMG) activity of the muscles and their asymmetry index, at
      mandibular rest position, and during maximal voluntary clenching (MVC), and
      posturometric and stabilometric measurements of 25 patients (mean age 28+/-9
      years) having undergone ACL injury of the left knee were compared with a control
      non-pathologic group. RESULTS: At rest, the patients showed a higher sEMG
      activity of the anterior temporalis, masseter, sternocleidomastoid and lower
      trapezius, compared with the control subjects (P<0.05). At MVC, the patients
      showed a lower sEMG activity of the right anterior temporalis and masseter and a
      higher sEMG activity of the lower trapezius, compared with the control subjects.
      For the stabilometric measurements, all the subjects showed a significant
      reduction in the Center of Pressure (CoP) path length during the test with eyes
      open and cotton rolls, compared with the test with eyes closed and mandibular
      rest position (P<0.05). In addition, the patients showed a significant
      displacement of the CoP in a forward direction (P<0.05) and to the righ side
      (P<0.05), compared with the control-subjects during each test. CONCLUSIONS: ACL
      injury appears to be associated to a change in the sEMG activity of head, neck
      and trunk muscles and to a change in the position of the CoP of the body. Cotton
      rolls seem to improve the stability of the subject.

PMID- 16456518
TI  - Positional changes of hyoid bone and cranio-cervical posture following class III
      orthopedic treatment.
AB  - AIM: The purpose of this study was to evaluate hyoid changes after skeletal class
      III therapy and, particularly, after chin-cup and Delaire face mask treatment.
      METHODS: This analysis was carried out by taking pretreatment (T1) and
      posttreatment (T2) lateral cephalometric radiographs of 30 patients (18 males and
      12 females) with craniofacial skeletal class III cephalometrics traits; their
      age, at the time of starting treatment, ranged from 9 years to 13 years and 2
      months, with an average of 11.02+/-1.23. RESULTS: In the 2 samples there were
      highly significant differences for H-H1 (P<0.01), C3-H and hyoid angle, which
      mean an inferior hyoid bone position with a decrease of distance between
      mandibula, vertebral column and hyoid bone. Postural items showed a highly
      significant posterior inclination of the cervical vertebral column; in chin-cup
      subjects there was a hypoextension of the head. CONCLUSIONS: The inferior
      position of the hyoid bone, in both the samples examined, and the hypoextension
      of the head, could point out the function of hyoid bone as an ''organ of
      respiration'' , since the variation of its position, as a sign of a new muscular
      equilibrium, should help to maintain the patency of the upper airways.

PMID- 16456519
TI  - Dental anxiety in adolescent people.
AB  - AIM: Anxiety in adolescence is a complex phenomenon, but could affect oral
      hygiene and compliance to dental therapies in young people. METHODS: Owing to the
      importance of anxiety in coping with odontostomatologic therapy, 2 groups of
      adolescent subjects (age range 16-20 years) have been compared: a group of
      patients under treatment at the Policlinico Gemelli (45 subjects, 27 females and
      18 males) and a control group of students (39 subjects, 20 females and 19 males).
      Different aspects of anxiety have been analysed by the STAI Y-I test (state
      anxiety), STAI Y-2 test (trait anxiety) and the Dental Anxiety Scale, on the
      basis of the hypothesis that the group of patients should show higher anxiety
      levels as to state anxiety and dental anxiety. Data were evaluated by the
      analysis of variance method and Student's t test as regards mean differences.
      RESULTS: The group of patients showed significantly higher state anxiety than
      controls, and significant differences as to trait anxiety were also found. In
      both groups girls were significantly more anxious than boys. Our results confirm
      the hypothesis that high anxiety levels are related to odontostomatologic
      treatments. Patients from Policlinico Gemelli showed a significantly better
      knowledge of dental hygiene than control group. CONCLUSIONS: A better knowledge
      of dental hygiene is not sufficient to reduce anxiety. Preventive measures that
      could reduce anxiety and ensure a better compliance in adolescent patients are
      thus discussed.

PMID- 16456520
TI  - Implant surface and osseointegration.
AB  - Oral rehabilitation by means of osteointegrated implants is gaining more and more
      importance, in particular due to the improved characteristics of the fixture:
      among these, the superficial microscopical morphology plays a role of primary
      importance, since it can influence the evolution of the osteointegrative process.
      Therefore, this led to many surface treatments which can improve the quality and
      the speed of formation of the bony tissue. The aim of this paper is a review of
      the literature on this topic in order to find out which processes of
      characterization of the surface implant are now available and which results can
      be obtained.

PMID- 16456522
TI  - Glomus tumor of the lower lip. A case report.
AB  - A glomus tumor is a benign neoplasm originating from the modified smooth muscle
      cells of the vascular glomus. This neoplasm was firstly considered by Masson in
      1924, and generally it has a solitary lesions but in some cases multiple lesions
      were described. Differential diagnosis is usually made with Kaposi sarcoma and
      hemangiopericytoma. The histopathologic examination is essential together with
      the immunohistochemical study. The clinical case of a 65-year-old man with a
      glomus tumor of the lower lip is described.

PMID- 16456521
TI  - Vaccines and prevention in dental care.
AB  - As epidemiological data demonstrate, dental workers are exposed during their
      activity to a biological risk that may result in serious damages for their
      health. Vaccination practice is one of the main instruments for prevention of
      infectious diseases, and thus an important measure for protection of dental
      personnel. The authors report current obligatory and recommended vaccinations for
      health-care workers in Italy, which may be applied to the dental staff. For each
      vaccine-preventable disease, a comparison with American guidelines is carried
      out. Vaccines for other infectious diseases, that may be employed for protection
      of dental personnel, were also considered.

PMID- 16456523
TI  - Pachyonychia congenita. Case report.
AB  - A 17-year old female patient was referred to our Department. Clinical examination
      revealed white, hyperkeratotic lesions on the dorsal part of the tongue, together
      with symmetric lesions on the buccal mucosa. The patient also showed dystrophic
      changes of the nails, both on hands and on feet, as well as bullous lesions on
      the soles. After detailed clinical and histologic examinations, diagnosis of
      pachyonychia congenita was made.

PMID- 16456524
TI  - Assessment of health-related needs after tsunami and earthquake--three districts,
      Aceh Province, Indonesia, July-August 2005.
AB  - On December 26, 2004, an earthquake measuring 9.2 on the Richter scale off the
      northwest coast of the island of Sumatra, Indonesia, produced a tsunami that
      caused the deaths of an estimated 230,000 persons in India, Indonesia, the
      Maldives, Somalia, Sri Lanka, and Thailand. The majority of casualties were in
      Aceh Province (population 4.5 million) in northern Sumatra, Indonesia, where an
      estimated 130,000 persons died. In addition, 500,000 persons were displaced from
      their homes, and 37,000 remain unaccounted for in the province. In the Aceh
      Province districts of Banda Aceh and Aceh Besar, an estimated 90,000 persons
      died; approximately 75% of health workers in Banda Aceh either died or were
      displaced from their homes. On March 28, 2005, a second major earthquake,
      measuring 8.7 on the Richter scale, caused large-scale damage to the islands of
      Simeulue and Nias off the western Sumatra coast; approximately 300 persons died,
      and thousands were displaced. The international community responded to these
      events with the largest relief measures ever undertaken for a natural disaster.
      To determine the health and nutrition status of the affected populations and to
      evaluate the effectiveness of relief interventions 7 months after the tsunami and
      3 months after the second earthquake, Cooperative for Assistance and Relief
      Everywhere, Inc. (CARE) International Indonesia and CDC conducted surveys in
      three districts of Aceh Province (Aceh Besar, Banda Aceh, and Simeulue). This
      report summarizes the results of those surveys, which identified routine
      vaccinations and provision of toilets or latrines as particular areas for
      improvement and revealed no significant difference in health indicators between
      internally displaced persons (IDPs) and nondisplaced populations. The relief
      response in Aceh Province should target areas needing improvement with programs
      that serve both IDPs and nondisplaced persons, as measures are implemented to
      rebuild the public health infrastructure.

PMID- 16456525
TI  - Imported vaccine-associated paralytic poliomyelitis--United States, 2005.
AB  - Paralytic poliomyelitis is rare in the United States because of the success of
      universal childhood immunization and the Global Polio Eradication Initiative.
      Poliovirus vaccine was introduced in the 1950s. Since then, the United States has
      eliminated indigenous wild poliovirus transmission, controlled imported wild
      poliovirus cases, and, through a vaccine policy change (i.e., from live,
      attenuated oral polio vaccine [OPV] to inactivated polio vaccine [IPV]),
      eliminated vaccine-associated paralytic polio (VAPP) cases. The most recent VAPP
      case occurred in 1999. The primary risk for paralytic polio for U.S. residents is
      through travel to countries where polio remains endemic or where polio outbreaks
      are occurring. This report describes the first known occurrence of imported VAPP
      in an unvaccinated U.S. adult who traveled abroad, where she likely was exposed
      through contact with an infant recently vaccinated with OPV. This case highlights
      the previously unrecognized risk for paralytic polio among unvaccinated persons
      exposed to OPV during travel abroad.

PMID- 16456526
TI  - Childhood influenza vaccination coverage--United States, 2003-04 influenza
      season.
AB  - Children aged <2 years are at increased risk for influenza-related
      hospitalizations. Beginning in 2002, the Advisory Committee on Immunization
      Practices (ACIP) encouraged that, when feasible, children aged 6-23 months and
      household contacts and out-of-home caregivers for children aged <2 years receive
      influenza vaccinations each year. Beginning with the 2004-05 influenza season,
      ACIP strengthened the encouragement to a recommendation. Other children
      recommended to receive influenza vaccination include children aged 6 months-18
      years who have certain high-risk medical conditions, are on chronic aspirin
      therapy, or who are household contacts of persons at high risk for influenza
      complications. This report provides an assessment of childhood influenza
      vaccination coverage for the 2003-04 influenza season, the second year of the
      ACIP encouragement for influenza vaccination of children aged 6-23 months. The
      findings demonstrate that vaccination coverage increased from the previous
      influenza season but remained low, with substantial variability among states and
      urban areas.

PMID- 16456527
TI  - Update: influenza activity--United States, January 15-21, 2006.
AB  - During January 15-21, 2006, the number of states reporting widespread influenza
      activity decreased to five. Twenty-three states reported regional activity, nine
      reported local activity, and 13 reported sporadic activity.

PMID- 16456528
TI  - Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.
AB  - CDC and the U.S. Food and Drug Administration rely on state and local health
      departments, health-care providers, and the public to report the occurrence of
      adverse events after vaccination to the Vaccine Adverse Event Reporting System.
      With such data, trends can be accurately monitored, unusual occurrences of
      adverse events can be detected, and the safety of vaccination intervention
      activities can be evaluated. On January 24, 2003, the U.S. Department of Health
      and Human Services (DHHS) implemented a preparedness program in which smallpox
      (vaccinia) vaccine was administered to federal, state, and local volunteers who
      might be first responders during a biologic terrorism event. As part of the DHHS
      Smallpox Preparedness and Response Program, CDC in consultation with experts,
      established surveillance case definitions for adverse events after smallpox
      vaccination. Adverse reactions after smallpox vaccination identified during the
      1960s surveillance activities were classified on the basis of clinical
      description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia;
      accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia;
      erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and
      pyogenic infection of the vaccination site. This report provides uniform criteria
      used for the surveillance case definition and classification for these previously
      recognized adverse reactions used during the DHHS Smallpox Preparedness and
      Response Program. Inadvertent inoculation was changed to more precisely describe
      this event as inadvertent autoinoculation and contact transmission, nonocular and
      ocular vaccinia. Pyogenic infection also was renamed superinfection of the
      vaccination site or regional lymph nodes. Finally, case definitions were
      developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac
      adverse event (dilated cardiomyopathy) and are included in this report. The
      smallpox vaccine surveillance case definitions presented in the report can be
      used in future vaccination programs to ensure uniform reporting guidelines and
      case classification.

PMID- 16456529
TI  - sPLA2-X stimulates cutaneous melanocyte dendricity and pigmentation through a
      lysophosphatidylcholine-dependent mechanism.
AB  - Photoprotection of the skin is provided by melanocytes, neural crest derived
      cells that synthesize melanin in specialized organelles that are transferred to
      keratinocytes. Secretory phospholipases comprise a large family of Ca2+-dependent
      enzymes that liberate arachidonic acid (AA), a precursor of prostaglandins, as
      well as lysophospholipids. The predominant secretory phospholipase expressed by
      keratinocytes is group X secretory phospholipase A2 (sPLA2), which liberates
      large amounts of AA and the lysophospholipid lysophosphatidylcholine (LPC), from
      membrane preparations. Recent work by our laboratory has shown that melanocytes
      express receptors for prostaglandins that upon activation stimulate melanocyte
      dendricity and activity of tyrosinase, a key enzyme in melanin biosynthesis. In
      the present study, we have treated human melanocytes with recombinant sPLA2-X and
      show that low levels of sPLA2-X stimulate both tyrosinase activity and melanocyte
      dendricity. We found that the effects of sPLA2-X are mediated predominantly by
      LPC, not AA, and we have demonstrated expression of the phospholipase A2 receptor
      and two G-protein-coupled receptors for LPC (G2A and GPR119) in human
      melanocytes. Because secretory phospholipases are released during inflammation
      and are regulated by UV irradiation, our data suggest an important role for sPLA2
      X in cutaneous pigmentation through the release of LPC.

PMID- 16456530
TI  - Male restricted genetic association of variant R620W in PTPN22 with psoriatic
      arthritis.

PMID- 16456532
TI  - CD8+ T cells are effector cells of contact dermatitis to common skin allergens in
      mice.
AB  - Allergic contact dermatitis (ACD) to strong experimental haptens is mediated by
      specific CD8+ T cells. Here, we show that similar mechanisms occur for weak
      haptens, which comprise the vast majority of chemicals responsible for human ACD.
      We used a model of ACD, that is, the contact hypersensitivity reaction, to test
      for the allergenicity of three weak haptens involved in fragrance allergy. ACD to
      weak haptens could not be induced in normal mice. In contrast, mice acutely
      depleted in CD4+ T cells developed a typical ACD reaction to the three weak
      fragrance allergens that peaked 24 hours after challenge. Priming of CD8+ T cells
      was observed in draining lymph nodes 5 days after sensitization and development
      of ACD was associated with the infiltration of activated CD8+ T cells in the
      challenged skin. CD8+ T cells were effectors of the ACD reaction as in vivo
      treatment with depleting anti-CD8 mAbs abrogated the ACD responses and as
      purified CD8+ T cells could adoptively transfer ACD to naive recipients. In
      conclusion, our data demonstrate a dominant role of CD8+ T cells as initiators of
      ACD to weak haptens, and suggest that CD8+ T cells may represent potential
      targets for preventing or treating ACD.

PMID- 16456531
TI  - Engagement of CD47 inhibits the contact hypersensitivity response via the
      suppression of motility and B7 expression by Langerhans cells.
AB  - CD47 is a membrane-associated glycoprotein that suppresses the function of immune
      cells. We previously reported that Langerhans cells (LCs) express Src homology 2
      domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1), a ligand for
      CD47, which plays an important role in the regulation of their motility. In this
      study, we show that LCs also express CD47, and that ligation of CD47 with SHPS-1
      Fc fusion protein in vivo diminishes the development of the contact
      hypersensitivity response. We further demonstrate that CD47 engagement affects
      immune functions of LCs. CD47 engagement in vivo significantly inhibits the
      emigration of LCs from the epidermis into draining lymph nodes following
      treatment with haptens and tumor necrosis factor-alpha. The emigration of
      dendritic cells from skin explants into the medium and the chemotaxis of murine
      XS52 dendritic cells were significantly reduced by treatment with SHPS-1-Fc or an
      anti-CD47 mAb. Under explant culture system, SHPS-1-Fc treatment suppressed the
      expression of CD80 and CD86 of LCs. These effects on LCs and contact
      hypersensitivity response of CD47 ligation were reversed by treatment with
      pertussis toxin. These results suggest that the ligation of CD47 inhibits the
      migration of LCs and the expression of B7 costimulatory molecules, which results
      in inhibition of the contact hypersensitivity response.

PMID- 16456534
TI  - Ligand-independent activation of the EGFR by lipid raft disruption.
AB  - Normal and immortalized keratinocytes demonstrate large aggregates of lipid
      rafts, detectable by membrane staining with fluorescently tagged cholera toxin
      (CTx). As lipid rafts are known to regulate the function of many surface
      receptors, we wished to investigate their impact on the EGFR in HaCaT cells. When
      rafts were disrupted by cholesterol sequestration with methyl-beta-cyclodextrin
      (MbetaCD) or filipin III, EGFR rearranged into approximately micrometer large
      clusters outside the CTx(bright) raft aggregates. These clusters contained high
      concentrations of activated, tyrosine-phosphorylated EGFR exhibiting greatly
      reduced mobility in the fluorescence recovery after photobleaching experiments.
      EGFR activation led to the stimulation of extracellular signal-regulated kinase
      2, the phosphorylated form of which translocated to the nucleus and stimulated
      growth of the MbetaCD-treated cells. Experiments with the specific antagonistic
      antibody proved that the activation of EGFR by lipid raft disruption occurred
      without the participation of the ligand. We hypothesize that cholesterol
      depletion leads to the release of EGFR from the damaged rafts into the small
      confined areas of the membrane, where the receptor molecules are likely to be
      spontaneously activated owing to a very high density and/or separation from the
      inhibitory factors remaining in the surrounding portions of the membrane.

PMID- 16456533
TI  - Mice transgenic for Kit(V620A): recapitulation of piebaldism but not progressive
      depigmentation seen in humans with this mutation.
AB  - Piebaldism is an autosomal dominant genetic pigmentary disorder, characterized by
      congenital white hair and patches located on the forehead, anterior trunk, and
      extremities. Most piebald patients have a mutation of the KIT gene, which encodes
      a tyrosine kinase receptor involved in pigment cell development. The white hair
      and patches of such patients are already completely formed at birth and do not
      usually expand thereafter. This stability of pigmented spots also applies to
      Kit(W) and Kitl(Sl) mutant mice. However, two novel cases of piebaldism were
      reported in 2001, in which both mother and daughter having a novel Val620Ala
      mutation in their KIT gene showed progressive depigmentation. To prepare an
      animal model of this mutation, to explore undefined functions of KIT signaling
      for maintaining pigmented melanocytes in the skin or more specifically the
      integrity of the melanocyte stem cell system in the postnatal skin, we produced
      transgenic mice expressing Val620Ala Kit. These mice well mimicked the white
      spotting pattern of patients; however, no change in this pattern was observed
      after birth, even after increasing the transgene expression by various means.
      Here, we report the unexpectedly extremely stable maintenance of the melanocyte
      stem cell system under stringent conditions for KIT signaling.

PMID- 16456535
TI  - Quantification of eight tissue kallikreins in the stratum corneum and sweat.

PMID- 16456536
TI  - Novel functions of intracellular IL-1ra in human dermal fibroblasts: implications
      in the pathogenesis of fibrosis.
AB  - Intracellular IL-1 receptor antagonist (icIL-1ra) is reportedly involved in
      functions independent of blocking IL-1 receptor signaling. Fibroblasts derived
      from the involved skin of patients with systemic sclerosis (SSc) are
      predominantly of the myofibroblast phenotype, with higher levels of icIL-1ra
      compared to normal skin fibroblasts. We examined the effect of overexpression of
      icIL-1ra on the phenotype and function of normal fibroblasts with respect to the
      expression of alpha smooth muscle actin (alpha-SMA), a specific marker for
      myofibroblasts, and plasminogen activator inhibitor (PAI), a protein involved in
      fibrogenesis and expressed at higher levels in myofibroblasts, and the production
      of collagenase (matrix metalloproteinase-1 (MMP-1)), the major enzyme involved in
      the degradation of native collagen in the skin. Normal human foreskin fibroblasts
      overexpressing icIL-1ra showed higher levels of alpha-SMA and PAI and had lower
      levels of collagenase and MMP-1 mRNA induced by inflammatory cytokines. By
      contrast, levels of mRNA for tissue inhibitor of metalloproteinase-1 in the
      transfected cells were not different from the control cells. Pretreatment of the
      ic-IL-1ra-transfected cells with antisense oligonucleotide directed against the
      mRNA of icIL-1ra restored MMP-1 expression induced by stimulation with IL-1beta.
      Our data indicate novel functions for icIL-1ra, which might be relevant to the
      genesis of fibrotic diseases such as SSc.

PMID- 16456538
TI  - Transferrin receptor-like proteins control the degradation of a yeast metal
      transporter.
AB  - Plasma membrane transporters are often downregulated by their substrates. The
      yeast manganese transporter Smf1 is subject to two levels of regulation: heavy
      metals induce its sequestration within the cell, and also its ubiquitination and
      degradation in the vacuole. Degradation requires Bsd2, a membrane protein with a
      PPxY motif that recruits the ubiquitin ligase Rsp5, and which has a role in the
      quality control of membrane proteins, that expose hydrophilic residues to the
      lipid bilayer. We show that degradation of Smf1 requires in addition one of a
      pair of related yeast proteins, Tre1 and Tre2, that also contain PPxY motifs.
      Tre1 can partially inhibit manganese uptake without Bsd2, but requires Bsd2 to
      induce Smf1 degradation. It has a relatively hydrophilic transmembrane domain and
      binds to Bsd2. We propose that the Tre proteins specifically link Smf1 to the
      Bsd2-dependent quality control system. Their luminal domains are related to the
      transferrin receptor, but these are dispensable for Smf1 regulation. Tre proteins
      and the transferrin receptors appear to have evolved independently from the same
      family of membrane-associated proteases.

PMID- 16456537
TI  - Suppression of Egr-1 transcription through targeting of the serum response factor
      by oncogenic H-Ras.
AB  - The transcription factor Egr-1 functions as a key regulator in cellular growth,
      differentiation, and apoptosis. The loss of Egr-1 expression is closely
      associated with tumor development, although the molecular mechanism behind the
      suppression of Egr-1 is largely unknown. In this report, we show that growth
      factor-induced transcriptional activation of Egr-1 gene is downregulated by
      chronic expression of oncogenic H-Ras in NIH3T3 fibroblasts. Our results
      demonstrate that phosphoinositide 3-kinase (PI3K) signaling is necessary for
      oncogenic H-Ras-mediated reduction of Egr-1 gene expression. Aberrant activation
      of PI3K signaling by oncogenic Ras decreased the level of serum response factor
      (SRF) protein through the acceleration of proteolysis, which resulted in
      decreased SRF binding to the serum response element (SRE) sites within the Egr-1
      promoter, leading to the suppression of Egr-1 transcription. Inhibition of PI3K
      signaling restored the downregulation of SRF and Egr-1 expression caused by
      oncogenic Ras. Our findings suggest a novel signaling mechanism by which
      prolonged activation of oncogenic H-Ras can trigger the loss of tumor suppressor
      Egr-1 through the PI3K pathway in NIH3T3 fibroblast model cell lines.

PMID- 16456539
TI  - A unique set of SH3-SH3 interactions controls IB1 homodimerization.
AB  - Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components
      of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is
      expressed at high levels in neurons and in pancreatic beta-cells, where it
      controls expression of several insulin-secretory components and secretion. IB1
      has been shown to homodimerize, but neither the molecular mechanisms nor the
      function of dimerization have yet been characterized. Here, we show that IB1
      homodimerizes through a novel and unique set of Src homology 3 (SH3)-SH3
      interactions. X-ray crystallography studies show that the dimer interface covers
      a region usually engaged in PxxP-mediated ligand recognition, even though the IB1
      SH3 domain lacks this motif. The highly stable IB1 homodimer can be significantly
      destabilized in vitro by three individual point mutations directed against key
      residues involved in dimerization. Each mutation reduces IB1-dependent basal JNK
      activity in 293T cells. Impaired dimerization also results in a reduction in
      glucose transporter type 2 expression and in glucose-dependent insulin secretion
      in pancreatic beta-cells. Taken together, these results indicate that IB1
      homodimerization through its SH3 domain has pleiotropic effects including
      regulation of the insulin secretion process.

PMID- 16456540
TI  - P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARalpha
      mediated transcription.
AB  - Nuclear retinoic acid (RA) receptors (RARs) activate gene expression through
      dynamic interactions with coregulators in coordination with the ligand and
      phosphorylation processes. Here we show that during RA-dependent activation of
      the RARalpha isotype, the p160 coactivator pCIP/ACTR/AIB-1/RAC-3/TRAM-1/SRC-3 is
      phosphorylated by p38MAPK. SRC-3 phosphorylation has been correlated to an
      initial facilitation of RARalpha-target genes activation, via the control of the
      dynamics of the interactions of the coactivator with RARalpha. Then,
      phosphorylation inhibits transcription via promoting the degradation of SRC-3. In
      line with this, inhibition of p38MAPK markedly enhances RARalpha-mediated
      transcription and RA-dependent induction of cell differentiation. SRC-3
      phosphorylation and degradation occur only within the context of RARalpha
      complexes, suggesting that the RAR isotype defines a phosphorylation code through
      dictating the accessibility of the coactivator to p38MAPK. We propose a model in
      which RARalpha transcriptional activity is regulated by SRC-3 through coordinated
      events that are fine-tuned by RA and p38MAPK.

PMID- 16456541
TI  - B56-containing PP2A dephosphorylate ERK and their activity is controlled by the
      early gene IEX-1 and ERK.
AB  - The protein phosphatase 2A (PP2A) acts on several kinases in the extracellular
      signal-regulated kinase (ERK) signaling pathway but whether a specific holoenzyme
      dephosphorylates ERK and whether this activity is controlled during mitogenic
      stimulation is unknown. By using both RNA interference and overexpression of PP2A
      B regulatory subunits, we show that B56, but not B, family members of PP2A
      increase ERK dephosphorylation, without affecting its activation by MEK.
      Induction of the early gene product and ERK substrate IEX-1 (ier3) by growth
      factors leads to opposite effects and reverses B56-PP2A-mediated ERK
      dephosphorylation. IEX-1 binds to B56 subunits and pERK independently, enhances
      B56 phosphorylation by ERK at a conserved Ser/Pro site in this complex and
      triggers dissociation from the catalytic subunit. This is the first demonstration
      of the involvement of B56-containing PP2A in ERK dephosphorylation and of a B56
      specific cellular protein inhibitor regulating its activity in an ERK-dependent
      fashion. In addition, our results raise a new paradigm in ERK signaling in which
      ERK associated to a substrate can transphosphorylate nearby proteins.

PMID- 16456542
TI  - PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor
      signaling.
AB  - PTEN, a tumor suppressor frequently inactivated in many human cancers, directly
      antagonizes the activity of phosphatidylinositol-3-OH kinase (PI3K) by
      dephosphorylating phosphoinositides. We show here that PTEN interacts directly
      with the NHERF1 and NHERF2 (Na+/H+ exchanger regulatory factor) homologous
      adaptor proteins through the PDZ motif of PTEN and the PDZ1 domain of NHERF1 or
      both PDZ domains of NHERF2. NHERFs were shown to interact directly with platelet
      derived growth factor receptor (PDGFR), and we demonstrate the assembly of a
      ternary complex between PTEN, NHERFs and PDGFR. The activation of the PI3K
      pathway after PDGFR stimulation was prolonged in NHERF1(-/-) mouse embryonic
      fibroblasts as compared to wild-type cells, consistent with defective PTEN
      recruitment to PDGFR in the absence of NHERF1. Depletion of NHERF2 by small
      interfering RNA similarly increased PI3K signaling. Phenotypically, the loss of
      NHERF1 enhanced the PDGF-induced cytoskeletal rearrangements and chemotactic
      migration of the cells. These data indicate that, in normal cells, NHERF proteins
      recruit PTEN to PDGFR to restrict the activation of the PI3K.

PMID- 16456543
TI  - Molecular analysis of receptor protein tyrosine phosphatase mu-mediated cell
      adhesion.
AB  - Type IIB receptor protein tyrosine phosphatases (RPTPs) are bi-functional cell
      surface molecules. Their ectodomains mediate stable, homophilic, cell-adhesive
      interactions, whereas the intracellular catalytic regions can modulate the
      phosphorylation state of cadherin/catenin complexes. We describe a systematic
      investigation of the cell-adhesive properties of the extracellular region of
      RPTPmu, a prototypical type IIB RPTP. The crystal structure of a construct
      comprising its N-terminal MAM (meprin/A5/mu) and Ig domains was determined at 2.7
      A resolution; this assigns the MAM fold to the jelly-roll family and reveals
      extensive interactions between the two domains, which form a rigid structural
      unit. Structure-based site-directed mutagenesis, serial domain deletions and cell
      adhesion assays allowed us to identify the four N-terminal domains (MAM, Ig,
      fibronectin type III (FNIII)-1 and FNIII-2) as a minimal functional unit.
      Biophysical characterization revealed at least two independent types of
      homophilic interaction which, taken together, suggest that there is the potential
      for formation of a complex and possibly ordered array of receptor molecules at
      cell contact sites.

PMID- 16456544
TI  - MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin
      remodeling and cell migration.
AB  - Vascular endothelial growth factor-A (VEGF-A) induces actin reorganization and
      migration of endothelial cells through a p38 mitogen-activated protein kinase
      (MAPK) pathway. LIM-kinase 1 (LIMK1) induces actin remodeling by phosphorylating
      and inactivating cofilin, an actin-depolymerizing factor. In this study, we
      demonstrate that activation of LIMK1 by MAPKAPK-2 (MK2; a downstream kinase of
      p38 MAPK) represents a novel signaling pathway in VEGF-A-induced cell migration.
      VEGF-A induced LIMK1 activation and cofilin phosphorylation, and this was
      inhibited by the p38 MAPK inhibitor SB203580. Although p38 phosphorylated LIMK1
      at Ser-310, it failed to activate LIMK1 directly; however, MK2 activated LIMK1 by
      phosphorylation at Ser-323. Expression of a Ser-323-non-phosphorylatable mutant
      of LIMK1 suppressed VEGF-A-induced stress fiber formation and cell migration;
      however, expression of a Ser-323-phosphorylation-mimic mutant enhanced these
      processes. Knockdown of MK2 by siRNA suppressed VEGF-A-induced LIMK1 activation,
      stress fiber formation, and cell migration. Expression of kinase-dead LIMK1
      suppressed VEGF-A-induced tubule formation. These findings suggest that MK2
      mediated LIMK1 phosphorylation/activation plays an essential role in VEGF-A
      induced actin reorganization, migration, and tubule formation of endothelial
      cells.

PMID- 16456545
TI  - Activation of p38 MAP kinase by DNA double-strand breaks in V(D)J recombination
      induces a G2/M cell cycle checkpoint.
AB  - Delay of cell cycle progression in response to double-strand DNA breaks (DSBs) is
      critical to allow time for DNA repair and prevent cellular transformation. Here,
      we show that the p38 mitogen-activated protein (MAP) kinase signaling pathway is
      activated in immature thymocytes along with TcRbeta gene V(D)J recombination.
      Active p38 MAP kinase promotes a G2/M cell cycle checkpoint through the
      phosphorylation and activation of p53 in these cells in vivo. Inactivation of p38
      MAP kinase and p53 is required for DN3 thymocytes to exit the G2/M checkpoint,
      progress through mitosis and further differentiate. We propose that p38 MAP
      kinase is activated by V(D)J-mediated DSBs and induces a p53-mediated G2/M
      checkpoint to allow DNA repair and prevent cellular transformation.

PMID- 16456546
TI  - The structure of a protein primer-polymerase complex in the initiation of genome
      replication.
AB  - Picornavirus RNA replication is initiated by the covalent attachment of a UMP
      molecule to the hydroxyl group of a tyrosine in the terminal protein VPg. This
      reaction is carried out by the viral RNA-dependent RNA polymerase (3D). Here, we
      report the X-ray structure of two complexes between foot-and-mouth disease virus
      3D, VPg1, the substrate UTP and divalent cations, in the absence and in the
      presence of an oligoadenylate of 10 residues. In both complexes, VPg fits the RNA
      binding cleft of the polymerase and projects the key residue Tyr3 into the active
      site of 3D. This is achieved by multiple interactions with residues of motif F
      and helix alpha8 of the fingers domain and helix alpha13 of the thumb domain of
      the polymerase. The complex obtained in the presence of the oligoadenylate showed
      the product of the VPg uridylylation (VPg-UMP). Two metal ions and the catalytic
      aspartic acids of the polymerase active site, together with the basic residues of
      motif F, have been identified as participating in the priming reaction.

PMID- 16456547
TI  - Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic
      exit via Cdc20.
AB  - Fertilizable mammalian oocytes are arrested at the second meiotic metaphase (mII)
      by the cyclinB-Cdc2 heterodimer, maturation promoting factor (MPF). MPF is
      stabilized via the activity of an unidentified cytostatic factor (CSF), thereby
      suspending meiotic progression until fertilization. We here present evidence that
      a conserved 71 kDa mammalian orthologue of Xenopus XErp1/Emi2, which we term
      endogenous meiotic inhibitor 2 (Emi2) is an essential CSF component. Depletion in
      situ of Emi2 by RNA interference elicited precocious meiotic exit in maturing
      mouse oocytes. Reduction of Emi2 released mature mII oocytes from cytostatic
      arrest, frequently inducing cytodegeneration. Mos levels autonomously declined to
      undetectable levels in mII oocytes. Recombinant Emi2 reduced the propensity of
      mII oocytes to exit meiosis in response to activating stimuli. Emi2 and Cdc20
      proteins mutually interact and Cdc20 ablation negated the ability of Emi2 removal
      to induce metaphase release. Consistent with this, Cdc20 removal prevented
      parthenogenetic or sperm-induced meiotic exit. These studies show in intact
      oocytes that the interaction of Emi2 with Cdc20 links activating stimuli to
      meiotic resumption at fertilization and during parthenogenesis in mammals.

PMID- 16456549
TI  - Enhancement of Ad5-TRAIL cytotoxicity against renal cell carcinoma with histone
      deacetylase inhibitors.
AB  - Renal cell carcinoma (RCC) will cause greater than 12,000 deaths in the United
      States this year. The lack of effective therapy for disseminated RCC has
      stimulated the search for novel treatments including immunotherapeutic
      strategies, but poor therapeutic responses and marked toxicity have limited their
      use. The tumor necrosis factor (TNF) family member TNF-related apoptosis-inducing
      ligand (TRAIL)/Apo-2L induces apoptosis in various tumor cell types, while having
      little cytotoxicity against normal cells. In this study, we investigated the
      tumoricidal potential of a recombinant adenovirus encoding human TNFSF10 (Ad5
      TRAIL), alone and in combination with a panel of histone deacetylase inhibitors
      (HDACi), against the TRAIL/Apo-2L-resistant RCC line 786-O and normal human renal
      proximal tubule epithelial cells (RPTEC). Ad5-TRAIL was unable to induce
      apoptosis in either 786-O or RPTEC alone; however, tumor cell apoptosis occurred
      when Ad5-TRAIL was combined with HDAC inhibition. Except when combined with
      trichostatin A, RPTEC were not sensitized to Ad5-TRAIL by HDACi. In 786-O, HDAC
      inhibition induced CAR expression, permitting increased adenoviral infection and
      transgene expression. It also induced TRAIL-R2 expression, accelerated the death
      inducing signaling complex formation and enhanced caspase-8 activation. Our
      results demonstrate the utility of combining Ad5-TRAIL with HDACi against RCC,
      and mechanistically define how this combination modulates RCC sensitivity to
      TRAIL/Apo-2L and adenoviral infection.

PMID- 16456548
TI  - B-cell activation by membrane-bound antigens is facilitated by the interaction of
      VLA-4 with VCAM-1.
AB  - VCAM-1 is one of the main ligands of VLA-4, an integrin that is highly expressed
      on the surface of mature B cells. Here we find that coexpression of VCAM-1 on an
      antigen-bearing membrane facilitates B-cell activation. Firstly, this is achieved
      by mediating B-cell tethering, which in turn increases the likelihood of a B cell
      to be activated. Secondly, VLA-4 synergizes with the B-cell receptor (BCR),
      providing B cells with tight adhesion and enhanced signalling. This dual role of
      VCAM-1 in promoting B-cell activation is predominantly effective when the
      affinity of the BCR for the antigen is low. In addition, we show that the VCAM-1
      ectodomain alone is sufficient to carry out this function. However, it requires
      the transmembrane domain to segregate properly into a docking structure
      characteristic of the B-cell immunological synapse (IS). These results show that
      the VLA-4/VCAM-1 interaction during membrane antigen recognition enhances B-cell
      activation and this function appears to be independent of its final peripheral
      localization at the IS.

PMID- 16456550
TI  - Endostatin therapy reveals a U-shaped curve for antitumor activity.
AB  - Developing continuous systemic delivery of endostatin has been a goal of many
      laboratories. We have employed a method of gene therapy utilizing different viral
      constructs. Here, we report that a new serotype of adeno-associated viruses,
      which incorporates canine endostatin, provides dose-dependent transgene
      expression in the circulation after intramuscular injection in mice. Elevated
      levels of endostatin remained stable in the circulation for at least 4 months. In
      vitro assays determined that the protein expressed was biologically active.
      Antitumor activities of the above construct demonstrated a U-shape curve, where
      the maximum activity was observed within a certain critical concentration range.
      These data suggest that an optimum dose range may be required to achieve
      therapeutic efficacy in large animal models.

PMID- 16456551
TI  - Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by
      therapeutic vaccination with MVA E2 recombinant vaccine.
AB  - Human papillomavirus (HPV) is the etiologic agent for cervical cancer. In Mexico,
      a women dies every 2 h, and since 1990 the statistics have shown that the numbers
      of deaths are increasing. We conducted a phase II clinical trial to evaluate the
      potential use of the MVA E2 recombinant vaccinia virus in treating high-grade
      lesions (CIN 2 and CIN 3) associated with oncogenic papillomavirus. Fifty-four
      female patients with high degree lesions were treated either with an MVA E2
      therapeutic vaccine or with conization. Thirty-four women received the
      therapeutic vaccine, at a total of 10(7) virus particles per dose injected
      directly into the uterus once every week over a 6-week period. Twenty control
      patients were treated with conization. By colposcopy, 19 patients out of 34
      showed no lesion, in three patients the lesions were reduced by 85-90%, in eight
      other lesions had reduced by 60%, and in four more patients, they were reduced by
      25%. Histological analysis showed total elimination of high-grade lesions in 20
      out of 34 patients after treatment with MVA E2. Eleven patients had a 50%
      reduction in lesion size. In two other patients, the lesion was reduced to CIN 2
      and in one more patient the lesion was reduced to low grade (CIN 1). All patients
      developed antibodies against the MVA E2 vaccine, and generated a specific
      cytotoxic response against papilloma-transformed cells. DNA viral load was
      significantly reduced in MVA E2-treated patients. Conization eliminated the
      lesions in 80% of the patients, but patients did not develop cytotoxic activity
      specific against cancer cells and did not eliminate the papillomavirus. In
      addition, three patients treated with conization had recurrence of lesions 1 year
      later. These results show that therapeutic vaccination with MVA E2 proved to be
      very effective in stimulating the immune system against papillomavirus, and in
      generating regression of high-grade lesion.

PMID- 16456552
TI  - Characterization of an immuno 'stealth' derivative of the herpes simplex virus
      thymidine-kinase gene.
AB  - The cellular immune response against transgene-encoded neoantigens is a potential
      hurdle in gene therapy applications where long-term expression of transgenes is
      desired. Here a new optimized derivative of the herpes simplex virus 1-thymidine
      kinase (HSV1-TK) gene is described. The HSV-TK gene is frequently used in
      experimental studies on gene-directed enzyme prodrug therapy. In the optimized
      gene, the HSV-TK coding region is fused with the codons for the Gly-Ala repeat of
      the Epstein-Barr virus nuclear-antigen 1 to prevent proteasomal degradation of
      the HSV-TK. To measure the protective effect in vitro, a model cytotoxic T
      lymphocyte epitope derived from the ovalbumin was inserted in the TK. Cells
      expressing the GAr-modified TK do not present TK-derived peptides in the major
      histocompatibility complex. Furthermore, conservative nucleotide substitutions
      were introduced, which prevent splicing, as well as mutations that render the TK
      expressing cells more sensitive to ganciclovir (GCV). The GAr HSV-TK fusion
      protein is fully functional in vitro. This HSV-TK gene may be especially useful
      in those gene therapy applications where an immune response against the transgene
      encoded product would frustrate the treatment.

PMID- 16456553
TI  - The 'tipping point' applied.

PMID- 16456554
TI  - Dietary supplements in the US: pitfalls and safety.

PMID- 16456568
TI  - Does patient selection influence the outcome of capsule endoscopy in patients
      with chronic gastrointestinal bleeding?

PMID- 16456569
TI  - Is adult-to-adult living donor liver transplantation a viable option for liver
      replacement?

PMID- 16456570
TI  - Branched-chain amino-acid granules: can they improve survival in patients with
      liver cirrhosis?

PMID- 16456571
TI  - How useful is integrated PET and CT for the management of pancreatic cancer?

PMID- 16456572
TI  - Can MRCP replace ERCP in the diagnosis of congenital bile-duct cysts?

PMID- 16456573
TI  - What is the long-term efficacy of percutaneous ethanol injection for small
      hepatocellular carcinoma?

PMID- 16456574
TI  - Peptic ulcer disease today.
AB  - Over the past few decades, since the introduction of histamine H(2)-receptor
      antagonists, proton-pump inhibitors, cyclo-oxygenase-2-selective anti
      inflammatory drugs (coxibs), and eradication of Helicobacter pylori infection,
      the incidence of peptic ulcer disease and ulcer complications has decreased.
      There has, however, been an increase in ulcer bleeding, especially in elderly
      patients. At present, there are several management issues that need to be solved:
      how to manage H. pylori infection when eradication failure rates are high; how
      best to prevent ulcers developing and recurring in nonsteroidal anti-inflammatory
      drug (NSAID) and aspirin users; and how to treat non-NSAID, non-H. pylori
      associated peptic ulcers. Looking for H. pylori infection, the overt or
      surreptitious use of NSAIDs and/or aspirin, and the possibility of an acid
      hypersecretory state are important diagnostic considerations that determine the
      therapeutic approach. Combined treatment with antisecretory therapy and
      antibiotics for 1-2 weeks is the first-line choice for H. pylori eradication
      therapy. For patients at risk of developing an ulcer or ulcer complications, it
      is important to choose carefully which anti-inflammatory drugs, nonselective
      NSAIDs or coxibs to use, based on a risk assessment of the patient, especially if
      the high-risk patient also requires aspirin. Testing for and eradicating H.
      pylori infection in patients is recommended before starting NSAID therapy, and
      for those currently taking NSAIDs, when there is a history of ulcers or ulcer
      complications. Understanding the pathophysiology and best treatment strategies
      for non-NSAID, non-H. pylori-associated peptic ulcers presents a challenge.

PMID- 16456575
TI  - Pathophysiology, diagnosis and current management of chronic constipation.
AB  - Chronic constipation is prevalent in Western countries and is a complaint that is
      commonly seen in clinical practice. Only a relatively small percentage of
      constipated patients seek medical evaluation and most can be managed
      satisfactorily with first-line, conservative therapy. In patients with severe,
      refractory constipation, additional studies of colonic and anorectal function
      have clinical utility, as such patients are candidates for therapies not given to
      most constipated patients. This article reviews the modern principles and
      therapies used to manage chronic constipation of varying severities.

PMID- 16456576
TI  - A methodologic analysis of chemoprevention and cancer prevention strategies for
      gastrointestinal cancer.
AB  - Gastroenterology lags behind other specialties such as cardiology in the quality
      of its evidence base for clinical practice. One area where this is particularly
      evident is in cancer prevention, despite developments in chemoprevention
      strategies for high-risk patients. For chemoprevention strategies to be
      successful, we need appropriate clinical networks and translational science
      infrastructures, model chemoprevention agents and multiple, large, flexible and
      randomized clinical trials. Translational science must also be embedded into
      large-scale, long-term, randomized clinical trials that have hard endpoints, so
      that irrefutable evidence of the longevity of treatment efficacy can be gathered.
      We also need to be able to identify an individual's cancer risk using valid
      global patient populations, so that medical benefits can be applied to all,
      regardless of ethnicity, sex, economic status, age and comorbidities. The future
      success of gastrointestinal chemoprevention relies on fostering a closer link
      between basic pharmaceutical research and clinical applications, in a 'bench to
      bedside and back' manner. In this review we systematically assess the evidence
      for various cancer prevention strategies, especially chemoprevention, and
      highlight the obstacles to further exploitation of this knowledge base.

PMID- 16456577
TI  - A patient with long-standing iron-deficient anemia.
AB  - BACKGROUND: A 36-year-old Chinese woman presented with cutaneous lupus and was
      incidentally found to have iron-deficient anemia. She had a history of iron
      deficient anemia 13 years previously, for which extensive investigations were
      carried out; the results of which were all normal. The patient also had pulmonary
      tuberculosis at that time, for which she received a full course of treatment. She
      required periodic blood transfusions and iron supplements to maintain her
      hemoglobin levels. She was subsequently discharged to a family clinic for follow
      up until the current presentation. INVESTIGATIONS: Upper endoscopy, colonoscopy,
      barium meal follow-through, small-bowel enema, (99m)Tc-labeled red-cell scan and
      double-balloon enteroscopy. DIAGNOSIS: Iron-deficient anemia due to obscure
      gastrointestinal bleeding caused by two small-bowel hemangiomas. MANAGEMENT:
      Laparoscopic surgery.

PMID- 16456578
TI  - Chemotherapy resistance of glioblastoma stem cells.

PMID- 16456579
TI  - The NF-kappaB-mediated control of the JNK cascade in the antagonism of programmed
      cell death in health and disease.
AB  - NF-kappaB/Rel transcription factors have recently emerged as crucial regulators
      of cell survival. Activation of NF-kappaB antagonizes programmed cell death (PCD)
      induced by tumor necrosis factor-receptors (TNF-Rs) and several other triggers.
      This prosurvival activity of NF-kappaB participates in a wide range of biological
      processes, including immunity, lymphopoiesis and development. It is also crucial
      for pathogenesis of various cancers, chronic inflammation and certain hereditary
      disorders. This participation of NF-kappaB in survival signaling often involves
      an antagonism of PCD triggered by TNF-R-family receptors, and is mediated through
      a suppression of the formation of reactive oxygen species (ROS) and a control of
      sustained activation of the Jun-N-terminal kinase (JNK) cascade. Effectors of
      this antagonistic activity of NF-kappaB on this ROS/JNK pathway have been
      recently identified. Indeed, further delineating the mechanisms by which NF
      kappaB promotes cell survival might hold the key to developing new highly
      effective therapies for treatment of widespread human diseases.

PMID- 16456580
TI  - Hypoxia and HIF-1alpha protect A549 cells from drug-induced apoptosis.

PMID- 16456581
TI  - Prostaglandin-induced programmed cell death in Trypanosoma brucei involves
      oxidative stress.
AB  - Recently, we reported the induction of a programmed cell death (PCD) in
      bloodstream forms of Trypanosoma brucei by prostaglandin D(2) (PGD(2)). As this
      prostanoid is readily metabolized in the presence of albumin, we were prompted to
      investigate if PGD(2) metabolites rather than PGD(2) itself are responsible for
      the observed PCD. In fact, J series metabolites, especially PGJ(2) and
      Delta(12)PGJ(2), were able to induce PCD more efficiently than PGD(2). However,
      the stable PGD(2) analog 17phenyl-trinor-PGD(2) led to the same phenotype as the
      natural PGD(2), indicating that the latter induces PCD as well. Interestingly,
      the intracellular reactive oxygen species (ROS) level increased significantly
      under J series metabolites treatment and, incubation with N-acetyl-L-cysteine or
      glutathione reduced ROS production and cell death significantly. We conclude that
      PGJ(2) and Delta(12)PGJ(2) formation within the serum represents a mechanism to
      amplify PGD(2)-induced PCD in trypanosomes via ROS production.

PMID- 16456582
TI  - The myb-related gene stonewall induces both hyperplasia and cell death in
      Drosophila: rescue of fly lethality by coexpression of apoptosis inducers.
AB  - We carried out gain-of-function mutagenesis screening and identified a mutant in
      which GAL4 induction led to both hyperplasia and apoptosis. The gene involved was
      identified as stonewall (stwl), a myb-related gene involved in germ cell
      proliferation and differentiation during oogenesis. As observed with dmyb, the
      ectopic expression of stwl(UY823) inhibited endoreplication in salivary glands.
      We also found that stwl(UY823) overexpression, like overexpression of the wild
      type gene, activated G1/S transition and apoptosis. The apoptosis triggered by
      stwl(UY823) expression is correlated to induction of the proapoptotic gene
      reaper. Finally, the death of flies induced by ectopic stwl(UY823) expression is
      efficiently prevented in vivo by triggering cell death in stwl(UY823)-expressing
      cells. Our results suggest that stwl(UY823) kills flies by causing inappropriate
      cell cycle entry, and that triggering the death of these overproliferating cells
      or slowing their proliferation restores viability.

PMID- 16456584
TI  - The impact of HIV on sub-Saharan African eye departments.

PMID- 16456583
TI  - Virally mediated MafB transduction induces the monocyte commitment of human CD34+
      hematopoietic stem/progenitor cells.
AB  - Upregulation of specific transcription factors is a generally accepted mechanism
      to explain the commitment of hematopoietic stem cells along precise maturation
      lineages. Based on this premise, transduction of primary hematopoietic
      stem/progenitor cells with viral vectors containing the investigated
      transcription factors appears as a suitable experimental model to identify such
      regulators. Although MafB transcription factor is believed to play a role in the
      regulation of monocytic commitment, no demonstration is, to date, available
      supporting this function in normal human hematopoiesis. To address this issue, we
      retrovirally transduced cord blood CD34+ hematopoietic progenitors with a MafB
      cDNA. Immunophenotypic and morphological analysis of transduced cells
      demonstrated the induction of a remarkable monomacrophage differentiation.
      Microarray analysis confirmed these findings and disclosed the upregulation of
      macrophage-related transcription factors belonging to the AP-1, MAF, PPAR and MiT
      families. Altogether our data allow to conclude that MafB is a key regulator of
      human monocytopoiesis.

PMID- 16456586
TI  - Photodynamic therapy for solitary retinal metastasis from breast carcinoma.

PMID- 16456585
TI  - Tonometers and infectious risk: myth or reality? Efficacy of different
      disinfection regimens on tonometer tips.
AB  - PURPOSE: To evaluate the adequacy of common disinfection regimens for disposable
      tonometer tips and assess if disinfection of reusable prisms or the use of
      disposable tips is preferable. METHODS: We used disposable tonometer tips, using
      the same material and tip diameter of standard Goldmann tonometer prism. Strains
      of Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilisand Candida
      albicanswere tested according to the European standard guidelines for
      disinfectants test. Antimicrobial effectiveness of the following disinfection
      practices has been assessed: dry wipe, Minuten wipes (Alpro), soaking in 3%
      hydrogen peroxide, 0.5% benzalkonium chloride, and 0.5% Pantasept for 1, 5, and
      15 min. All tests have been performed three times and all conditions tested in
      duplicate. RESULTS: Dry wiping and 1 min soak in 3% hydrogen peroxide were
      ineffective on all microrganisms. Minuten wipes, 1 min soak in 0.5% benzalkonium
      chloride or 3% hydrogen peroxide were ineffective on B. subtilis. 0.5% Pantasept
      soak was effective in 1 min for all microrganisms tested, whereas 3% hydrogen
      peroxide and 0.5% benzalkonium chloride soaks were effective when performed for
      at least 5 min. B. subtiliswas the most resistant organism to disinfectant
      regimes at 1 min time. CONCLUSIONS: Results of our study demonstrate a relative
      disinfection efficacy for the different evaluated regimens, provided that correct
      exposure times are adopted for the chosen disinfectants, a condition difficult to
      ensure in a busy clinic setting. We conclude that disposable prism tonometry
      provides a safe alternative to Goldmann tonometry.

PMID- 16456587
TI  - Safety of Triamcinolone acetonide (TA)-assisted pars plana vitrectomy in macular
      hole surgery.
AB  - AIM: To evaluate whether Triamcinolone acetonide (TA)-assisted pars plana
      vitrectomy for visualisation of posterior hyaloid during macular hole surgery has
      any adverse effects on macular hole closure rate and intraocular pressure (IOP).
      METHODS: Case series comparing outcomes and adverse effects in patients who had
      surgery for macular holes with ILM peel, with and without the use of TA-assisted
      vitrectomy. RESULTS: During the study period, 29 patients had vitrectomy for
      macular holes. In 18 patients (group 1), TA was used intraoperatively to
      facilitate visualisation of the posterior hyaloid and in 11 patients (group 2) no
      TA was used. There was no statistically significant difference in the macular
      hole closure rates and the improvement in visual acuity between the two groups.
      No long-term increase in IOP was recorded in any of the 29 patients. The total
      anatomical success rate in both groups was 85.6% and the average improvement in
      visual acuity in both groups was two Snellen lines. CONCLUSIONS: TA is safe and
      there is no contraindication for its use as an intraoperative aid to facilitate
      vitreous visualisation in macular hole surgery.

PMID- 16456588
TI  - Pericentral pigmentary retinopathy: long-term follow-up.

PMID- 16456589
TI  - Adverse skin reactions to infliximab in the treatment of intraocular
      inflammation.
AB  - TNFalpha inhibitors are more widely used in the treatment of intraocular
      inflammation, thus ophthalmologists should become aware of possible adverse
      events, associated with this form of treatment. Herein we report two cases of
      cutaneous adverse events in uveitis patients treated with infliximab. In one
      patient, the primary outbreak of pustular psoriasis was observed after her third
      infusion. A second patient developed impetigo contagiosa induced by
      Staphylococcus aureus. Thus patients undergoing treatment with infliximab should
      be monitored carefully since dermal infections and pustular psoriasis, which may
      be triggered by streptococcal infection, may occur under this regime.

PMID- 16456590
TI  - How effective is macula-off retinal detachment surgery. Might good outcome be
      predicted?
AB  - PURPOSE: To determine factors associated with anatomical and functional outcomes
      of macula-off retinal detachment surgery in a modern vitreoretinal unit. METHODS:
      A retrospective casenote review of 185 patients presenting with macula-off
      retinal detachment was performed. Demographic and ocular characteristics were
      determined. Logistic regression analysis was used to determine (1) the effect of
      these factors on visual outcome and (2) their effect on primary and final
      anatomical success. RESULTS: Primary and ultimate anatomical success were
      achieved in 76 and 84% of cases. Patients with oil in at final follow-up were
      considered to be anatomical failures. Statistically significant factors
      predicting primary anatomical success using a multiple variable model were
      preoperative logMAR visual acuity, preoperative PVR and number of breaks. Preop
      logMAR visual acuity and duration of macular detachment were the statistically
      significant factors predicting ultimate success. In all, 44% of patients regained
      6/12 Snellen or better with a median improvement of 0.78 logMAR. For prediction
      of visual outcome (in patients with no ocular comorbidity) only preoperative
      logMAR visual acuity achieved statistical significance (P=0.001) at the P=0.05
      level. CONCLUSION: In all, 76% of macula-off detachments may be repaired with one
      operation and 44% of patients regain at least 6/12 Snellen. The median logMAR
      acuity increment of 0.78 far exceeds that seen in cataract surgery. Preoperative
      visual acuity is the most important factor predicting primary and final
      anatomical success as well as visual outcome. Preoperative PVR, number of breaks
      and duration of detachment also affect outcomes.

PMID- 16456591
TI  - Bilateral vitreous haemorrhage associated with dengue fever.

PMID- 16456592
TI  - The prevalence of low vision and blindness in a Canadian inner city.
AB  - PURPOSE: To ascertain the prevalence and primary causes of visual impairment in a
      sample of patients from Vancouver's downtown eastside (VDES). MATERIALS AND
      METHODS: A total of 200 patients seeking nonophthalmic medical care at the
      Vancouver Native Health Society (VNHS) clinic in Vancouver's inner city (downtown
      eastside) participated in this observational case-series study. For each
      participant, we obtained demographic information, a medical and ocular history,
      and performed a complete eye exam. The prevalence of visual disability using
      standard North American criteria was reported. Causes of visual loss were also
      reported based on Canadian National Institute for the Blind (CNIB) guidelines.
      RESULTS: A total of 200 patients participated in our study. The median age of our
      sample was 46 years, 69% were male. There were very high rates of comorbid
      medical conditions including HIV, Hepatitis B/C, IV drug use, and diabetes. The
      raw prevalence of visual disability based on best-corrected visual acuity (BCVA)
      was 500 per 10,000; this was over nine times greater than in the general Canadian
      population. The raw prevalence rate of 'presenting visual disability' based on
      presenting visual acuity (PVA) was 2400 per 10,000. Major causes of visual
      disability were cataract and retinal disease. Although age-related macular
      degeneration and diabetic retinopathy represent major causes of vision loss in
      North America, no cases were noted in our sample. CONCLUSION: The overall
      prevalence of visual disability was alarmingly high in this disadvantaged
      community. These results identify both ophthalmic disease and access to
      refraction and prescription spectacles as a significant health concern among
      people living in the VDES.

PMID- 16456593
TI  - Quality of life and visual rehabilitation: an observational study of low vision
      in three general practices in West Glamorgan.
AB  - AIM: To survey low vision in an urban population and assess impact on quality of
      life, rehabilitation and support. METHODS: In a cross-sectional population
      survey, 66 patients were identified from databases of three general practices and
      surveyed by investigator administered questionnaire. Main outcome measures were
      ocular diagnoses, (US) National Eye Institute Visual Function-Questionnaire (NEI
      VFQ) scores assessing visual and nonvisual disability, eligibility for, awareness
      and receipt of rehabilitation and support. RESULTS: Of 24,420 individuals on the
      lists of the three study practices, we found 101 registered as blind or partially
      sighted (prevalence 0.41%). A total of 66 patients participated with ocular
      diseases of age-related macular degeneration 39 (59%), glaucoma 11 (17%),
      diabetic retinopathy two (3%), retinitis pigmentosa two (3%), and 12 (18%)
      'others'. Better eye visual acuity was counting fingers or worse in 32 (48.5%).
      NEI-VFQ scores were poor-overall mean 41.5% (SD 23.5). In all, 80% had a social
      services home visit with one-third of these still in contact. In all, 66% had
      undergone a low vision aid assessment and 57.6% of these used their aid. The
      awareness and receipt of benefits arising from registration as visually impaired
      were lower than for other supportive measures available for reasons unrelated to
      vision. None had a guide dog. CONCLUSIONS: We found expected patterns of low
      vision but poorer levels of function and support that may reflect age and
      deprivation in a population failed by the current systems for identification,
      registration, and rehabilitation based on legislation overtaken by demographic
      change and social provision independent of visual status.

PMID- 16456594
TI  - Assessment of spatial-contrast function and short-wavelength sensitivity deficits
      in patients with migraine.
AB  - AIMS: To study spatial-contrast function and short-wavelength sensitivity
      deficits in a migraine population with a disease duration of 30 years or less.
      MATERIALS AND METHODS: In this prospective, cross-sectional study, we evaluated
      28 subjects with migraine headache and 15 nonheadache healthy controls. Visual
      fields were evaluated using the Humphrey Field Analyzer 750i and the 30-2, blue
      and yellow threshold programme. Contrast sensitivity (CS) was measured at 1.5, 3,
      6, 12, and 18 cpd spatial frequencies, using the Functional Acuity Contrast Test
      (F.A.C.T.). The results of the visual field parameters (mean defect (MD) and
      pattern standard defect (PSD)) and CS were compared with 15 age-equivalent normal
      subjects. RESULTS: Short-wavelength amplitude perimetry (SWAP) parameters and CS
      scores at all spatial frequencies were significantly altered in the migraine
      patients when compared with the control subjects. Visual field parameters
      correlated significantly with contrast sensitivity scores: positively for MD
      (r=0.39, P=0.01; r=0.43, P=0.005; r=0.56, P=0.0001; r=0.45, P=0.003; r=0.48,
      P=0.0001) and negatively for PSD (r=-0.45, P=0.003; r=-0.45, P=0.003; r=-0.51,
      P=0.001; r=-0.53, P=0.0001; and r=-0.67, P=0.0001) at all (1.5, 3, 6,12, and 18
      cpd) spatial frequencies, respectively. Migraine duration correlated negatively
      with MD (r=-0.42, P=0.04) and positively with PSD (r=0.42, P=0.03). CONCLUSION:
      Migraineurs had significantly altered visual field and contrast function at all
      spatial frequencies to the normal population. These defects share some features
      with early stages of glaucoma and may relate a possibility for a common vascular
      disease pathogenesis in these two conditions.

PMID- 16456596
TI  - Pulsatile ocular blood flow in asymmetric age-related macular degeneration.
AB  - PURPOSE: Ocular perfusion abnormalities have been proposed in the pathogenesis of
      age-related macular degeneration (AMD) with differences in pulsatile ocular blood
      flow (POBF) in eyes with asymmetric AMD in Japanese and Taiwanese patients. The
      purpose of our study was to observe POBF difference in the fellow eyes of
      Caucasians with asymmetric AMD. METHODS: This was a cross-sectional study
      comparing POBF in three groups of patients with asymmetric AMD in the fellow
      eyes: Group 1 (n=21) with drusen and active choroidal neovascularisation (CNV);
      Group 2 (n=18) with drusen and disciform scar; Group 3 (n=8) with CNV and
      disciform scar. The POBF was adjusted for intraocular pressure (IOP), pulse rate
      (PR), and axial length using multiple regression analysis. Generalised estimation
      equation model was used to include both eyes in each group. RESULTS: The
      geometric mean (95% confidence interval) POBF values were as follows: Group 1
      with drusen 1097.9 microl/min (957.0, 1259.7) in one eye and the fellow eye with
      CNV 1090.1 microl/min (932.3, 1274.7); Group 2 with drusen 946.0 microl/min
      (794.2, 1126.7) and disciform scar 966.2 microll/min (780.3, 1196.4); Group 3
      with CNV 877.1 microl/min (628.3, 1224.6) and disciform scar 767.2 microl/min
      (530.5, 1109.7). Adjusting for differences in axial length, pulse rate and
      intraocular pressure, no statistically significant difference in POBF was found
      between fellow eyes in the same subject. CONCLUSIONS: POBF is not different
      between fellow eyes of Caucasian patients with asymmetric AMD.

PMID- 16456597
TI  - Evaluation of the effect of JPEG and JPEG2000 image compression on the detection
      of diabetic retinopathy.
AB  - AIMS: To compare the effect of classic Joint Photographic Experts Group (JPEG)
      and JPEG2000 compression algorithms on detection of diabetic retinopathy (DR)
      lesions. METHODS: In total, 45 colour fundus photographs obtained with a digital
      nonmydriatic fundus camera were saved in uncompressed Tagged Interchanged Files
      Format (TIFF) format (1.26 MB). They were graded jointly by two retinal
      specialists at a 1 month interval for soft exudates, hard exudates, macular
      oedema, newvessels, intraretinal microvascular abnormalities (IRMA), and retinal
      haemorrhages and/or microaneurysms. They were compressed to 118, 58, 41, and 27
      KB by both algorithms and 24 KB by classic JPEG, placed in random order and
      graded again jointly by the two retina specialists. Subjective image quality was
      graded, and sensitivity, specificity, positive and negative predictive values,
      and kappa statistic were calculated for all lesions at all compression ratios.
      RESULTS: Compression to 118 KB showed no effect on image quality and kappa values
      were high (0.94-1). Image degradation became important at 27 KB for both
      algorithms. At high compression levels, IRMA and HMA detection were most affected
      with JPEG2000 performing slightly better than classic JPEG. CONCLUSION:
      Performance of classic JPEG and JPEG2000 algorithms is equivalent when
      compressing digital images of DR lesions from 1.26 MB to 118 KB and 58 KB. Higher
      compression ratios show slightly better results with JPEG2000 compression, but
      may be insufficient for screening purposes.

PMID- 16456598
TI  - Report of a novel lobular chorioretinal dystrophy.

PMID- 16456599
TI  - Corneo-conjunctival carcinoma in Uganda.
AB  - AIMS: Since 1990, the incidence of conjunctival neoplasia has more than tripled
      in Uganda. It is known to be associated with exposure to solar ultraviolet
      radiation and to infection with the human immunodeficiency virus-1 (HIV).
      However, little is known about the most effective treatments. In this study, we
      report surgical outcomes among people with corneo-conjunctival squamous neoplasia
      in Uganda and investigate the role of HIV infection and other factors in the
      aetiology of the tumour. METHODS: Country-wide enrolment of participants; removal
      and histology of suspect lesions; HIV counselling and testing; home visiting of
      participants to determine outcomes. RESULTS: In 67 months between 1995 and 2001,
      476 participants were enrolled (262 female, 214 male, median age 32 years). A
      total of 463 (97%) had eye-conserving removal of the lesion and 13 had other
      surgery. For 414, the histology was squamous neoplasia (184 invasive carcinoma,
      230 intraepithelial). The prevalence of HIV infection in cases was 64%. In all,
      96% were followed up for a median period of 32 months (range 0-81) after eye
      conserving surgery during which time 13 (3.2%) had a recurrence. CONCLUSIONS:
      Surgery resulted in a low recurrence rate during the follow-up period and had
      minimal complications. The prevalence of HIV among cases was higher than expected
      on the basis of data from the general population, although about a third of cases
      were HIV-negative and had normal CD4 counts. No new cofactors were identified.

PMID- 16456600
TI  - Aortic graft infection: update on management and treatment options.
AB  - Replacement of the abdominal aorta, whether by autogenous or prosthetic conduit,
      has been an a priori requisite in the vascular surgeon's armamentarium since its
      technical feasibility was described in the early 1950s. The Achilles' heel of
      this operation, in spite of the progress made over the last half century, is
      still, however, aortic graft infection. Though survival and limb salvage rates
      have improved over time-commensurate with advances in surgical technique,
      critical care, and antimicrobial agents-the prevention and treatment of aortic
      graft infection remains a formidable challenge to the vascular surgeon. The
      authors herein review the current literature on this topic with an emphasis on
      the surgical management options available and suggest an individualized operative
      strategy based on patient as well as microbial factors to attain the best
      possible outcome.

PMID- 16456601
TI  - Outcome of surgical and endoluminal intervention for infrainguinal bypass
      anastomotic strictures.
AB  - The objective of this study was to compare the outcomes of percutaneous
      transluminal angioplasty (PTA) versus open surgical repair of anastomotic
      strictures affecting infrainguinal bypasses. Anastomotic strictures affecting 39
      bypasses in 36 patients were identified among 593 consecutive infrainguinal
      arterial reconstructions performed between 1994 and 2004. The mean age of
      affected patients was 65 +/- 2 years (range: 61 to 101 years). The original
      bypasses, with vein grafts outnumbering prosthetic grafts 2 to 1, were performed
      for acute (5%) and chronic (54%) limb-threatening ischemia, disabling
      claudication (28%), or popliteal aneurysms (13%). Anastomotic strictures were
      first recognized an average of 16 +/- 3 months (range 2 to 92 months)
      postoperatively. Strictures affected the distal anastomosis in 62% of cases and
      the proximal anastomosis in 38%. Primary patency, assisted primary patency,
      secondary patency, and limb salvage were assessed following PTA or open surgical
      repair of the strictures. Anastomotic strictures were detected following acute
      (41%) and chronic (18%) limb-threatening ischemia, claudication (13%), or during
      routine graft surveillance (28%) in asymptomatic patients. Graft thrombosis,
      occurring in 51% of patients at the time of presentation, was not affected by the
      site of anastomotic stricture, although prosthetic grafts were affected more than
      vein grafts (92% vs 31%). Interventions included PTA (67%) and conventional open
      procedures (33%). The latter included vein patch angioplasty, short interposition
      grafts, and redo bypasses. The stricture site and bypass material used in the
      original revascularization did not affect reintervention patency rates. Sixteen
      (62%) of the endovascular procedures were performed on a graft presenting with
      thrombosis, while only 4 (31%) were initially treated with operative therapy.
      Treatment of thrombosed grafts resulted in an 18-month patency of 32% compared to
      an 80% patency in treating grafts that were not occluded at the time of
      presentation (p < 0.05). No anastomotic stricture repaired operatively required
      reintervention, whereas 42% of those treated by PTA required a mean of 1.3
      additional reinterventions (p < 0.03). Anastomotic strictures affecting
      infrainguinal bypass grafts contribute to low patency rates. Outcomes can be
      significantly improved if these strictures are identified before graft
      thrombosis. Open surgical repair, compared to PTA, provides improved graft
      function as evident by fewer subsequent interventions required to maintain graft
      patency.

PMID- 16456602
TI  - Impact of duplex arteriography in the evaluation of acute lower limb ischemia
      from thrombosed popliteal aneurysms.
AB  - Acute limb-threatening ischemia from thrombosis may be the initial presentation
      of popliteal artery aneurysms (PAA) and is associated with amputation rates of 20
      30%. Since contrast angiography may miss the diagnosis, the authors suspect that
      thrombosis of PAA may be an underappreciated cause of acute ischemia. Routine use
      of duplex arteriography (DA) may aid in the diagnosis and may help identify the
      outflow vessels with improved results. One hundred and nine patients (group 1)
      from 1994 to 1997 and 201 patients from 1998 to 2001 (group 2) presenting with
      acute limb-threatening ischemia were studied. None of the group 1 patients
      underwent preoperative DA and no diagnosis of acute popliteal artery aneurysm
      thrombosis was made. Ten patients with acute ischemia due to thrombosed popliteal
      artery aneurysms were identified in group 2 when preoperative DA was routinely
      performed. Urgent revascularization based on the results from DA was performed
      with use of autogenous saphenous vein in all patients. Six patients had
      functioning bypasses with a mean follow-up of 15.6 months. There were 3 deaths, 2
      within 30 days and 1 after 2(1/2) years with functioning grafts. One patient was
      lost to follow-up. No major amputations were performed. Incidence of thrombosed
      popliteal artery aneurysms as the cause of acute limb-threatening ischemia is
      probably underestimated. Routine use of DA may provide the diagnosis and
      identifies the available outflow vessels. Contrary to previously published
      reports, urgent revascularization of an acutely ischemic extremity from
      thrombosed popliteal aneurysm can provide excellent rates of limb salvage.

PMID- 16456603
TI  - Endovascular therapy of symptomatic innominate-subclavian arterial occlusive
      lesions.
AB  - The purpose of this study was to determine the safety and efficacy of angioplasty
      and stenting for symptomatic innominate-subclavian lesions by review of records
      of symptomatic patients undergoing angioplasty and stenting of high-grade lesions
      (>80%) of the innominate and subclavian arteries. Follow-up consisted of history
      (symptoms) and physical examination (pulses and blood pressures) at 1, 3, 6, and
      then every 12 months plus an annual duplex ultrasound examination. Between 1998
      to 2003, 25 patients (27 lesions) were treated. Ages ranged from 48 to 89 years.
      Symptoms included vertebrobasilar/steal (15), claudication (6), ischemia (4), and
      coronary artery bypass grafting/left internal mammary artery (2). There were 7
      occlusions and 20 high-grade stenoses. Access was attempted via brachial cutdown
      (19) or percutaneous puncture of the brachial (2) or femoral arteries (10).
      Twenty-two lesions were stented with either self-expanding (13) or balloon
      expandable (9) stents. Technical success was 89%; 3 occluded lesions could not be
      crossed owing to complete occlusion. The remaining 4 occlusions were all crossed
      via a retrograde approach. The mean difference in systolic blood pressure between
      upper limbs decreased from 36 mm Hg (preprocedure) to 10 mm Hg (postprocedure).
      There were no procedure-related complications. Mean follow-up was 18 months
      (range 1-62 months). One patient died 4 months after the procedure secondary to
      complications from pulmonary surgery unrelated to the percutaneous transluminal
      angioplasty/stent. Of the 4 successfully treated occlusions, 2 were followed up
      to 3 years with continued patency. Three patients developed recurrent stenoses
      documented by duplex examination. However, these patients remained asymptomatic
      and were not treated. Endovascular management of high-grade lesions of the
      subclavian or innominate arteries is safe and efficacious and may be considered
      as a first line of therapy. Continued follow-up is needed to assess long-term
      patency.

PMID- 16456604
TI  - Outcomes of endovascular AAA repair in patients with hostile neck anatomy using
      adjunctive balloon-expandable stents.
AB  - Hostile neck anatomy remains the predominant reason that patients are denied
      endovascular aneurysm repair (EVAR). We reviewed our experience of EVAR with use
      of prophylactic adjunctive proximal balloon-expandable stents in patients with
      hostile neck anatomy and adjunctive proximal balloon-expandable stents in
      patients with type I endoleaks. Of 140 patients who underwent EVAR between 2000
      and 2004, we reviewed data for 19 patients in whom we used proximal balloon
      expandable stents. By high-resolution computed tomography scan or angiography,
      hostile neck anatomy was classified as length <15 mm, neck diameters > or =26 mm,
      circumferential thrombus at the proximal neck, angulated neck > or =60 degrees,
      and neck bulge or reverse taper necks. Patients were considered to have hostile
      anatomy if they met 1 or more of the above-cited criteria. All patients underwent
      AAA repair with commercially available endograft systems, Zenith (Cook,
      Bloomington, IN) and AneuRx (Medtronic/AVE, Minneapolis, MN). Balloon-expandable
      stents utilized included Cordis-Palmaz stents (17/19) and eV3 Max stents (2/19).
      Stents were deployed in the proximal graft with transrenal extension. AneuRx
      (18/19) and Zenith (1/19) endografts were used in all of the patients. Of the 19
      patients, 15 had prophylactic stent placement for known hostile neck anatomy and
      4 patients had stent placement for type I endoleak. Assisted primary technical
      success was achieved in all patients. Three patients had maldeployment of the
      endograft or proximal stent requiring additional endovascular interventions at
      the time of surgery. No endografts were deployed too low requiring stent
      placement. Procedure-related complications occurred in 2 of 19 patients. These
      included 1 operative death secondary to pneumonia and 1 patient who developed
      progressive renal failure. Short-term clinical success was achieved in 17 of 19
      patients. Two patients required secondary interventions, 1 due to device
      migration with secondary conversion to open repair, and an endoleak, which, on
      angiogram, was a large type II endoleak successfully treated with coiling of the
      inferior mesenteric artery. One patient was observed to have a type II endoleak
      with no associated aneurysm enlargement. Short-term results suggest the use of
      prophylactic adjunctive balloon-expandable stents may decrease the incidence of
      secondary interventions related to hostile neck anatomy when used as an
      adjunctive measure with EVAR. Based on our experience, we feel EVAR may be
      offered to an expanded patient population with hostile neck anatomy with use of
      prophylactic balloon-expandable stents.

PMID- 16456605
TI  - Can computed tomography scan findings predict "impending'' aneurysm rupture?
AB  - Several findings on computed tomography (CT) scans of intact aneurysms have been
      taken to suggest "imminent'' or "impending'' aneurysm rupture. Often these are
      identified incidentally in asymptomatic patients when an urgent operation was not
      planned and may even be ill advised. The authors evaluated whether these signs
      can truly predict short-term aneurysm rupture. A computerized medical archival
      system was reviewed from August 1994 to August 2004. Patients with aortic
      aneurysms and official CT scan reports of "impending rupture'' were reviewed. CT
      films and reports were reviewed for aneurysm characteristics, while computerized
      medical records were reviewed for patient demographics, comorbidities, symptoms,
      documented subsequent rupture, and operative findings. Signs of "impending
      rupture'' included the crescent sign, discontinuous circumaortic calcification,
      aortic bulges or blebs, aortic draping, and aortic wall irregularity. Rupture
      occurring within 2 weeks of the index CT was defined as supporting the
      "imminent'' label. Forty-five patients with aortic aneurysms and CT stigmata of
      "impending rupture'' were identified. Five patients with additional signs of
      suspicious leak and 1 with an infected previously repaired aneurysm were
      excluded. Of 39 intact aneurysms, 26 (67%) were infrarenal, 2 (5%) were
      suprarenal, and the remaining 11 (28%) were thoracoabdominal. The patient group
      had more women than expected (19/39, 49%) and larger aneurysms (mean diameter,
      6.8 +/- 1.4 cm). Mean age was 74 years. Ten patients underwent elective repair
      within the first 2 weeks after the index CT scan (mean, 4 days), precluding
      adequate observation for early rupture. None had intraoperative signs of rupture.
      Early rupture: 2 of the 29 remaining patients ruptured within 72 hours of the CT
      scan, for a positive predictive value of 6.9%. One additional patient ruptured 7
      months later after declining an early intervention. No Rupture: 26 patients were
      observed an average of 246 days (range, 14 days to 3 years) without evidence of
      rupture. Fourteen were repaired electively 2 weeks to 3 years after the index CT
      scan, and 12 never underwent repair, mostly because of severe associated
      comorbidities, and were observed a mean of 394 days without rupture. Although
      they should be taken seriously, CT signs of "impending rupture'' alone are poor
      predictors of short-term aortic aneurysm rupture, and alternative terminology is
      needed until better predictors can be identified.

PMID- 16456606
TI  - Pravastatin and clopidogrel combined inhibit intimal hyperplasia in a rat carotid
      endarterectomy model.
AB  - Intimal hyperplasia, resulting from a complex cascade of events involving
      platelets, leukocytes, and smooth muscle cells, may be inhibited by the HMG-CoA
      reductase inhibitor pravastatin, which demonstrates inhibition of platelet
      activity and leukocyte adhesion and may be associated with inhibition of vascular
      smooth muscle cell proliferation and migration. Clopidogrel, an adenosine
      diphosphate (ADP) receptor inhibitor, was shown to decrease platelet activity and
      aggregation but not intimal hyperplasia (IH). We postulated that the combination
      of both pravastatin and clopidogrel would significantly decrease IH in a rat
      carotid endarterectomy model. Male Sprague-Dawley rats (n = 18) divided by
      treatment regimen underwent treatment for 2 weeks both before and after an open
      carotid endarterectomy. Serum collected at the time of harvest was measured for C
      reactive protein (CRP), platelet activity, and total serum cholesterol; carotid
      arteries were removed and processed for IH determination. Control rats (n = 7)
      received oral vehicle daily before and following endarterectomy. Pravastatin
      alone rats (n = 6) received oral pravastatin (10 mg/kg/day) before and after
      endarterectomy. Pravastatin plus clopidogrel rats (n = 5) received oral
      pravastatin (10 mg/kg/day) plus a preendarterectomy bolus of oral clopidogrel
      (4.3 mg/kg) before endarterectomy and resumed pravastatin (10 mg/kg/day) plus
      oral clopidogrel (1 mg/kg/day) postendarterectomy. Pravastatin alone and
      pravastatin plus clopidogrel significantly decreased CRP compared to controls
      (120.2 +/-11.2 and 134.1 +/- 9.9 vs 191.1 +/- 9.2 microg/mL, respectively p =
      0.003 and p =0.0024). CRP levels were not different between pravastatin alone and
      pravastatin plus clopidogrel (p = 0.35). Platelet activity was significantly
      decreased by pravastatin alone and pravastatin plus clopidogrel in comparison to
      controls (7.3 +/- 2.2 and 6.6 +/- 2.8 vs 19.2 +/- 6.1 platelet reactive units
      (PRU), respectively p = 0.048 and p = 0.045). No significant difference was noted
      in platelet activity between pravastatin alone and pravastatin plus clopidogrel
      (p = 0.89). Pravastatin plus clopidogrel significantly reduced serum cholesterol
      compared to control and pravastatin alone (84.0 +/- 6.6 vs 110.4 +/- 7.4 and
      117.0 +/- 8.8 mg/dL, respectively p = 0.03 and p = 0.01). Pravastatin alone did
      not decrease serum cholesterol compared to controls (p = 0.54). IH was not
      reduced by pravastatin alone compared to controls (p = 0.61) but was
      significantly decreased by pravastatin plus clopidogrel in comparison to control
      and pravastatin alone (3.0 +/- 1.1 vs 46.3 +/- 13.7 and 37.4 +/- 14.6% luminal
      stenosis, respectively p = 0.01 and p = 0.05). Pravastatin plus clopidogrel
      significantly decreased CRP, platelet activity, total serum cholesterol, and IH
      while pravastatin alone decreased only CRP and platelet activity. Intimal
      hyperplasia reduction may therefore be dependent on other contributors, possibly
      growth factors, cytokines, and oxidative stress. The combination of pravastatin
      plus clopidogrel may have synergistic or even additional inhibitory effects on
      IH. Pravastatin plus clopidogrel was effective in decreasing IH in a rat carotid
      endarterectomy model and may prove a useful therapy for IH reduction in the
      clinical setting.

PMID- 16456607
TI  - Mitogen-activated protein kinase pathway regulates cell proliferation in venous
      ulcer fibroblasts.
AB  - Venous ulcer fibroblasts have been demonstrated to have low growth rates in
      response to platelet-derived growth factor (PDGF). Mitogen-activated protein
      kinase (MAPK) is an important signal transduction mechanism that regulates
      growth, differentiation, and apoptosis in eukaryotic cells. PDGF binds PDGF
      receptors that activate a multitiered signaling cascade involving MAPK. We
      hypothesize that the growth regulation in venous ulcer fibroblasts is dependent
      on the MAPK extracellular signal-regulated kinase (ERK) pathway in the presence
      of PDGF. Fibroblasts (fb) were isolated from 8 patients with venous ulcers (w-fb)
      and the normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fb were
      plated at 1,500 cells/dish and treated with PDGF-AB (10 ng/mL) for 15 days.
      Growth rates were determined. Immunoblot analysis of MAPK ERK for n-fb and w-fb
      were analyzed. To determine if PDGF-stimulated w-fb and n-fb utilized the MAPK
      ERK pathway in a dependent manner, the upstream kinase MAPK kinase 1 (MEK 1) was
      inhibited by PD 98059. In addition, fb were treated with chronic venous ulcer
      wound fluid (WF) to study its effect on MAPK ERK. In the presence of PDGF, growth
      rates were substantially lower in w-fb than in n-fb, and MAPK was activated in
      6/8 w-fb and in only 2/8 n-fb. Fibroblasts expressing MAPK had significantly
      reduced cell proliferation compared to fibroblasts not expressing MAPK (p =
      0.023). PD 98059 significantly inhibited w-fb and n-fb cell proliferation from
      basal level, which was reversible with addition of PDGF. In neonatal fibroblasts
      WF demonstrated inhibition of MAPK ERK over time and addition of PD98059 was not
      additive. This study suggests that the MAPK ERK pathway is important for cell
      proliferation in venous ulcer fibroblasts. In the presence of PDGF, fibroblasts
      with decreased growth rate express MAPK, and proliferation is further abrogated
      with addition of MEK 1 inhibitor, suggesting the importance of the MAPK ERK
      pathway regulating w-fb and n-fb proliferation. Although the majority of w-fb
      activated the MAPK ERK pathway in the presence of PDGF, proliferation was
      significantly attenuated, indicating that other MAPK inhibitory pathways are
      competing. Venous ulcer wound fluid directly inhibits the MAPK ERK pathway,
      suggesting that the venous ulcer wound environment has negative trophic factors
      that effect fibroblasts proliferation and ulcer healing.

PMID- 16456608
TI  - Delayed-onset heparin-induced thrombocytopenia and thrombosis after
      intraoperative heparin anticoagulation-four case reports.
AB  - Delayed-onset heparin-induced thrombocytopenia (HIT) is a rare and only recently
      described condition. The authors report 4 cases of delayed-onset HIT, each of
      which presented with thrombotic complications 8-18 days after receiving heparin
      for coronary artery bypass grafting. Delayed-onset HIT should be suspected in any
      patient presenting with arterial or venous thromboembolism after heparin therapy,
      even 1 to 3 weeks after heparin exposure.

PMID- 16456609
TI  - Ruptured popliteal artery aneurysm: a case report.
AB  - A high index of suspicion for popliteal aneurysms must be present when evaluating
      a popliteal mass. Though typically pulsatile, in the presence of chronic
      thrombosis, the absence of a pulse may make the diagnosis even more difficult. A
      case is presented that illustrates this point, where an 83-year-old man presents
      following the biopsy of what turned out to be a very large popliteal aneurysm. In
      the presence of chronic thrombosis and adequate collateral flow, decompression
      and ligation of any feeding vessels is typically sufficient. These patients must
      be followed lifelong for the development of other associated aneurysms.

PMID- 16456610
TI  - Ortner's syndrome and endoluminal treatment of a thoracic aortic aneurysm: a case
      report.
AB  - Left recurrent laryngeal nerve paralysis was first described in 1897 by Ortner in
      a patient with mitral valve disease. However, this paralysis has also been
      attributed to other cardiovascular pathologies, such as thoracic aortic
      aneurysms. In 1971, Parodi introduced the endoluminal technique by inserting
      endovascular prostheses for the treatment of vascular aneurysms. The authors
      present a case of acute dysphonia following left recurrent laryngeal nerve
      paralysis, confirmed by laryngoscopy, in a patient who was diagnosed with a
      saccular thoracic aortic aneurysm and treated with endovascular prostheses. It
      was not necessary to perform any additional surgical procedures on the vocal
      folds because the patient showed sufficient improvement during speech therapy.
      Follow-up exams at 3 and 6 months demonstrated the lack of any swallowing or
      respiratory disorders.

PMID- 16456611
TI  - Catheter embolization of an hepatic artery aneurysm: a case report.
AB  - Hepatic artery aneurysms (HAAs) are considered rare. The great improvement in the
      diagnosis of vascular diseases and the increasing incidence of atherosclerosis
      have resulted in a wider recognition of these pathologies. Differently from other
      splanchnic locations, HAAs have a high risk of rupture so that an aggressive
      treatment is required. Different therapeutic options are currently available:
      simple ligation of the artery, aneurysm excision with vascular reconstruction,
      and transcatheter embolization. We describe the usefulness of transcatheter
      arterial embolization of an 8 cm hepatic artery aneurysm incidentally found on an
      abdominal computed tomography (CT) scan in an asymptomatic patient.

PMID- 16456612
TI  - Biodegradation of crude oil by thermophilic bacteria isolated from a volcano
      island.
AB  - One-hundred and fifty different thermophilic bacteria isolated from a volcanic
      island were screened for detection of an alkane hydroxylase gene using
      degenerated primers developed to amplify genes related to the Pseudomonas putida
      and Pseudomonas oleovorans alkane hydroxylases. Ten isolates carrying the alkJ
      gene were further characterized by 16s rDNA gene sequencing. Nine out of ten
      isolates were phylogenetically affiliated with Geobacillus species and one
      isolate with Bacillus species. These isolates were able to grow in liquid
      cultures with crude oil as the sole carbon source and were found to degrade long
      chain crude oil alkanes in a range between 46.64% and 87.68%. Results indicated
      that indigenous thermophilic hydrocarbon degraders of Bacillus and Geobacillus
      species are of special significance as they could be efficiently used for
      bioremediation of oil-polluted soil and composting processes.

PMID- 16456614
TI  - Sulfidogenesis in low pH (3.8-4.2) media by a mixed population of acidophilic
      bacteria.
AB  - A defined mixed bacterial culture was established which catalyzed dissimilatory
      sulfate reduction, using glycerol as electron donor, at pH 3.8-4.2. The bacterial
      consortium comprised a endospore-forming sulfate reducing bacterium (isolate M1)
      that had been isolated from acidic sediment in a geothermal area of Montserrat
      (West Indies) and which had 94% sequence identity (of its 16S rRNA gene) to the
      Gram-positive neutrophile Desulfosporosinus orientis, and a Gram-negative (non
      sulfate-reducing) acidophile (isolate PFBC) that shared 99% gene identity with
      Acidocella aromatica. Whilst M1 was an obligate anaerobe, isolate PFBC, as other
      Acidocella spp., only grew in pure culture in aerobic media. Analysis of
      microbial communities, using a combination of total bacterial counts and
      fluorescent in situ hybridization, confirmed that concurrent growth of both
      bacteria occurred during sulfidogenesis under strictly anoxic conditions in a pH
      controlled fermenter. In pure culture, M1 oxidized glycerol incompletely,
      producing stoichiometric amounts of acetic acid. In mixed culture with PFBC,
      however, acetic acid was present only in small concentrations and its occurrence
      was transient. Since M1 did not oxidize acetic acid, it was inferred that this
      metabolite was catabolized by Acidocella PFBC which, unlike glycerol, was shown
      to support the growth of this acidophile under aerobic conditions. In fermenter
      cultures maintained at pH 3.8-4.2, sulfidogenesis resulted in the removal of
      soluble zinc (as solid phase ZnS) whilst ferrous iron remained in solution.
      Potential syntrophic interactions, involving hydrogen transfer between M1 and
      PFBC, are discussed, as is the potential of sulfidogenesis in acidic liquors for
      the selective recovery of heavy metals from wastewaters.

PMID- 16456613
TI  - Effect of modified Fenton's reaction on microbial activity and removal of PAHs in
      creosote oil contaminated soil.
AB  - This study describes the removal of polycyclic aromatic hydrocarbons (PAHs) from
      creosote oil contaminated soil by modified Fenton's reaction in laboratory-scale
      column experiments and subsequent aerobic biodegradation of PAHs by indigenous
      bacteria during incubation of the soil. The effect of hydrogen peroxide addition
      for 4 and 10 days and saturation of soil with H(2)O(2) on was studied. In both
      experiments the H(2)O(2) dosage was 0.4 g H(2)O(2)/g soil. In completely H(2)O(2)
      saturated soil the removal of PAHs (44% within 4 days) by modified Fenton
      reaction was uniform over the entire soil column. In non-uniformly saturated
      soil, PAH removal was higher in completely saturated soil (52% in 10 days)
      compared to partially saturated soil, with only 25% in 10 days. The effect of the
      modified Fenton's reaction on the microbial activity in the soil was assessed
      based on toxicity tests towards Vibrio fischeri, enumeration of viable and dead
      cells, microbial extracellular enzyme activity, and oxygen consumption and carbon
      dioxide production during soil incubation. During the laboratory-scale column
      experiments, the toxicity of column leachate towards Vibrio fischeri increased as
      a result of the modified Fenton's reaction. The activities of the microbial
      extracellular enzymes acetate- and acidic phosphomono-esterase were lower in the
      incubated modified Fenton's treated soil compared to extracellular enzyme
      activities in untreated soil. Abundance of viable cells was lower in incubated
      modified Fenton treated soil than in untreated soil. Incubation of soil in serum
      bottles at 20 degrees C resulted in consumption of oxygen and formation of carbon
      dioxide, indicating aerobic biodegradation of organic compounds. In untreated
      soil 20-30% of the PAHs were biodegraded during 2 months of incubation.
      Incubation of chemically treated soil slightly increased PAH-removal compared to
      PAH-removal in untreated soil.

PMID- 16456615
TI  - Admission blood glucose levels and early change of neurological grade in poor
      grade patients with aneurysmal subarachnoid haemorrhage.
AB  - BACKGROUND: The neurological grade of poor-grade subarachnoid haemorrhage (SAH)
      often changes soon after the patient is admitted to the hospital. It is important
      to closely monitor for such changes within a short period of time after
      admission; however, there are other problems that can occur during this time such
      as rebleeding. The aim of this study was to evaluate the relationship between
      admission blood glucose levels (ABGL) and early change of neurological grade
      after admission in patients with poor-grade SAH. METHODS: Forty-six patients with
      poor-grade SAH (Hunt & Kosnik Grade IV or V), who were admitted within 3 hrs
      after SAH onset, and who did not have haematomas causing mass effect, or a
      history of diabetes mellitus, were included in the study. Patients were
      pretreated to control blood pressure and intracranial pressure, and they were
      monitored for early change of grade after admission. Blood glucose level was
      measured at the time of admission. FINDINGS: Spontaneous grade improvement was
      observed in 9 of 17 Grade IV patients and 9 of 29 Grade V patients. The ABGL of
      the patients with grade improvement were significantly lower than the ABGL of the
      patients who did not improve or who got worse. ABGL were lower than 180 mg/dl in
      15 of 18 patients who showed grade improvement. CONCLUSIONS: Our results showed
      that there was a relationship between ABGL and neurological grade changes which
      were observed after admission in patients with poor-grade SAH. These results
      suggest that ABGL might be a useful parameter for making therapeutic decisions.

PMID- 16456616
TI  - Nephrin in human lymphoid tissues.
AB  - When nephrin, the protein product of NPHS1, was cloned, it was proposed to be
      specific for the kidney glomerular podocytes. Recently, however, new reports have
      emerged verifying additional nephrin expression sites, particularly the insulin
      producing beta cells of the pancreas, as well as the central nervous system. In
      this study, we demonstrate nephrin expression in lymphoid tissues, specifically
      the tonsil, adenoid and lymph node. Nephrin mRNA expression levels were 4-fold
      higher in tonsils and adenoids than in thymus or B lymphocytes, and 20-fold
      higher than in T lymphocytes or monocytes, as shown by quantitative RT-PCR
      analysis. Anti-nephrin antibodies recognised a specific 165-kDa band in lysates
      of tonsil and adenoid. In immunofluorescence and immunohistochemichal stainings
      of adenoid and lymph node sections, nephrin-positive cells were detected in the
      germinal centres of the lymphoid follicles in a staining pattern typical for
      interdigitating cells. These results indicate a definite and additional presence
      of nephrin in lymphoid tissue.

PMID- 16456617
TI  - On the self-association potential of transmembrane tight junction proteins.
AB  - Tight junctions seal intercellular clefts via membrane-related strands, hence,
      maintaining important organ functions. We investigated the self-association of
      strand-forming transmembrane tight junction proteins. The regulatory tight
      junction protein occludin was differently tagged and cotransfected in eucaryotic
      cells. These occludins colocalized within the plasma membrane of the same cell,
      coprecipitated and exhibited fluorescence resonance energy transfer. Differently
      tagged strand-forming claudin-5 also colocalized in the plasma membrane of the
      same cell and showed fluorescence resonance energy transfer. This demonstrates
      self-association in intact cells both of occludin and claudin-5 in one plasma
      membrane. In search of dimerizing regions of occludin, dimerization of its
      cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second
      extracellular loop was detected as a dimer. Since the transmembrane junctional
      adhesion molecule also is known to dimerize, the assumption that homodimerization
      of transmembrane tight junction proteins may serve as a common structural feature
      in tight junction assembly is supported.

PMID- 16456618
TI  - Unfaithfulness and promiscuity of a mutant androgen receptor in a hormone
      refractory prostate cancer.
AB  - Missense mutations in the androgen receptor (AR) contribute to the failure of
      hormonal therapy for prostate cancer (PCa), but the underlying molecular bases
      remain uncharacterized. Here, we describe a new AR variant found in a hormone
      refractory metastatic PCa, in which threonine 575 in the DNA binding domain, and
      threonine 877 in the ligand-binding domain, were both replaced by an alanine.
      Using gene reporter assays, we demonstrate that the T575A mutation weakened
      transcriptional activity from promoters containing AR-specific responsive
      elements, while activity from promoters with AR-non-specific elements was
      enhanced. Data from gel shift experiments revealed a preferential binding of the
      T575A mutant to AR-non-specific motifs. We demonstrate that the two mutations
      T575A and T877A cooperate to confer new functional properties on the AR, and that
      the mutant AR functions simultaneously as a promiscuous AR due to the T877A
      mutation, and an unfaithful AR due to the T575A mutation.

PMID- 16456619
TI  - Evaluation of Allen's test in both arms and arteries of left and right-handed
      people.
AB  - The Allen's test as described in 1929 by Edgar V. Allen has been modified,
      adapted and complemented by other newer modalities but remains a first line
      standard test to evaluate the arterial supply of the hand. In this study an
      attempt has been made to add more information regarding the arterial supply of
      the hand, in left- and right-handed individuals, left and right hands and the
      ulnar and radial arteries, when doing the Allen's test. A modified Allen's test
      using an oxygen saturation monitor was used. The sample group consisted of 80 (30
      left-handed and 50 right-handed) students. No significant differences between the
      Allen's test of the left and right hands in the left and right-handed individuals
      were found. There was a marginal but not significant difference between the two
      arteries. The ulnar artery took slightly longer to reach baseline values as
      compared to the radial artery. The results suggest that a positive Allen's test
      can be found in both left and right-handed people, with regard to the left and
      right hands and both radial and ulnar arteries may be implicated. This
      information should be kept in mind when selecting either the radial or ulnar
      artery for grafting purposes (e.g. coronary angiosurgery) and forearm artery
      cannulation.

PMID- 16456620
TI  - How can a surgeon be certain?

PMID- 16456622
TI  - Groundwater vulnerability assessment for organic compounds: fuzzy multi-criteria
      approach for Mexico city.
AB  - This study was based on a groundwater vulnerability assessment approach
      implemented for the Mexico City Metropolitan Area (MCMA). The approach is based
      on a fuzzy multi-criteria procedure integrated in a geographic information
      system. The approach combined the potential contaminant sources with the
      permeability of geological materials. Initially, contaminant sources were ranked
      by experts through the Analytic Hierarchy Process. An aggregated contaminant
      sources map layer was obtained through the simple additive weighting method,
      using a scalar multiplication of criteria weights and binary maps showing the
      location of each source. A permeability map layer was obtained through the
      reclassification of a geology map using the respective hydraulic conductivity
      values, followed by a linear normalization of these values against a compatible
      scale. A fuzzy logic procedure was then applied to transform and combine the two
      map layers, resulting in a groundwater vulnerability map layer of five classes:
      very low, low, moderate, high, and very high. Results provided a more coherent
      assessment of the policy-making priorities considered when discussing the
      vulnerability of groundwater to organic compounds. The very high and high
      vulnerability areas covered a relatively small area (71 km(2) or 1.5% of the
      total study area), allowing the identification of the more critical locations.
      The advantage of a fuzzy logic procedure is that it enables the best possible use
      to be made of the information available regarding groundwater vulnerability in
      the MCMA.

PMID- 16456623
TI  - Onsite sewage system regulation along the Great Lakes and the US EPA "Homeowner
      Awareness" model.
AB  - According to the United States Environmental Protection Agency (US EPA), a
      significant percentage of residential onsite sewage systems (OSSs) are failing at
      any given time. The US EPA has therefore issued a set of recommended guidelines
      for OSS regulatory programs aimed at reducing overall failure rates. We conducted
      a survey of OSS regulatory program administrators with jurisdictions bordering a
      Great Lake. Our goal was to determine their programs' capacities to meet the US
      EPA's recommendations. We found that although some local programs meet the US
      EPA's recommendations, most do not. In this article, we present our findings and
      conclusions for one of the US EPA's models, the baseline "Homeowner Awareness"
      model. Most areas do not have recommended requirements that systems be inspected
      when properties transfer between owners. A majority do not track changes in
      ownership within the computerized databases they use to record information about
      systems. Although most provide at least "one-time" information to homeowners
      regarding proper OSS maintenance, most do not contact them periodically with
      reminders of needed maintenance. We include recommendations for resolving some of
      the issues that our research identified.

PMID- 16456621
TI  - Isolation of myosin XI genes from the Closterium peracerosum-strigosum-littorale
      complex and analysis of their expression during sexual reproduction.
AB  - Myosins comprise a large superfamily of molecular motors that generate mechanical
      force in ATP-dependent interactions with actin filaments. On the basis of their
      conserved motor domain sequences, myosins can be divided into at least 17
      classes, 3 of which (VIII, XI, XIII) are found in plants. Although full sequences
      of myosins are available from several species of green plants, little is known
      about the functions of these proteins. Additionally, sequence information for
      algal myosin is incomplete, and little attention has been given to the molecular
      evolution of myosin from green plants. In the present study, the Closterium
      peracerosum-strigosum-littorale complex was used as a model system for
      investigating a unicellular basal charophycean alga. This organism has been well
      studied with respect to sexual reproduction between its two mating types. Three
      types of partial sequences belonging to class XI myosins were obtained using
      degenerate primers designed to amplify motor domain sequences. Real-time
      polymerase chain reaction analysis of the respective myosin genes during various
      stages of the algal life cycle showed that one of the genes was more highly
      expressed during sexual reproduction, and that expression was cell-cycle
      dependent in vegetatively grown cells.

PMID- 16456625
TI  - Learning about environments: the significance of primal landscapes.
AB  - The way we learn about our environments--be they farms, forests, or tribal lands-
      has implications for the formulation of environmental policy. This article
      presents the findings of how residents learned about their environments in two
      rural case studies conducted in northern Queensland and relates these to the
      concept of "primal landscapes," which is concerned with the interaction that
      occurs between children and the environments in which they mature. Rather than
      focusing specifically on built environments or natural environments, the article
      draws on an approach that conceptualizes environment as meaning-laden places in
      which we live and work, which integrate social, cultural, biological, physical,
      and economic dimensions. In drawing insights for environmental policy, the
      article draws attention to the timing of policy interventions, the significance
      of experiential environmental education, the potential to learn from place-based
      festivals, and the importance of learning from extreme events such as fires and
      floods.

PMID- 16456624
TI  - A spatially explicit resource-based approach for managing stream fishes in
      riverscapes.
AB  - The article describes a riverscape approach based on landscape ecology concepts,
      which aims at studying the multiscale relationships between the spatial pattern
      of stream fish habitat patches and processes depending on fish movements. A
      review of the literature shows that few operational methods are available to
      study this relationship due to multiple methodological and practical challenges
      inherent to underwater environments. We illustrated the approach with literature
      data on a cyprinid species (Barbus barbus) and an actual riverscape of the Seine
      River, France. We represented the underwater environment of fishes for different
      discharges using two-dimensional geographic information system-based maps of the
      resource habitat patches, defined according to activities (feeding, resting, and
      spawning). To quantify spatial patterns at nested levels (resource habitat patch,
      daily activities area, subpopulation area), we calculated their composition,
      configuration, complementation, and connectivity with multiple spatial analysis
      methods: patch metrics, moving-window analysis, and least cost modeling. The
      proximity index allowed us to evaluate habitat patches of relatively great value,
      depending on their spatial context, which contributes to the setting of
      preservation policies. The methods presented to delimit potential daily
      activities areas and subpopulation areas showed the potential gaps in the
      biological connectivity of the reach. These methods provided some space for
      action in restoration schemes.

PMID- 16456626
TI  - An evaluation of the influence of natural science in regional-scale restoration
      projects.
AB  - Regional-scale restoration is a tool of growing importance in environmental
      management, and the number, scope, and complexity of restoration programs is
      increasing. Although the importance of natural science to the success of such
      projects generally is recognized, the actual use of natural science in these
      programs rarely has been evaluated. We used techniques of program evaluation to
      examine the use of natural science in six American and three Western European
      regional-scale restoration programs. Our results suggest that ensuring the
      technical rigor and directed application of the science is important to program
      development and delivery. However, the influence of science may be constrained if
      strategies for its integration into the broader program are lacking.
      Consequently, the influence of natural science in restoration programs is
      greatest when formal mechanisms exist for incorporating science into programs,
      for example, via a framework for integration of science and policy. Our
      evaluation proposes a model that can be used to enhance the influence of natural
      science in regional-scale restoration programs in the United States and
      elsewhere.

PMID- 16456627
TI  - Governmental oversight of discharges from concentrated animal feeding operations.
AB  - As point sources of pollution in the United States, concentrated animal feeding
      operations (CAFOs) are subject to the National Pollution Discharge Elimination
      System permitting system requirements. Changes to federal regulations in 2003 and
      a 2005 court decision have increased the governmental oversight of CAFOs. Manure
      application to fields from "large CAFOs" that results in unpermitted discharges
      can be regulated under the Clean Water Act. The U.S. Environmental Protection
      Agency's interpretation of agricultural stormwater discharges was approved so
      that unpermitted discharges may arise if an owner or operator of a CAFO fails to
      apply manure correctly. Owners and operators do not, however, have a duty to
      secure governmental permits in the absence of a discharge. Turning to the federal
      provisions regarding nutrient management plans, a court found that they were
      deficient. Moreover, the federal government needs to reconsider requirements that
      would reduce pathogens from entering surface waters. Although these developments
      should assist in reducing the impairment of U.S. waters, concern still exists.
      Greater oversight of nutrient management plans and enhanced enforcement efforts
      offer opportunities to provide greater assurance that CAFO owners and operators
      will not allow a discharge of pollutants to enter surface waters.

PMID- 16456628
TI  - Effectiveness of management interventions to control invasion by Rhododendron
      ponticum.
AB  - Rhododendron ponticum is an invasive species in many countries, including the
      United Kingdom, Ireland, Belgium, and France. It poses a serious threat to native
      flora and fauna, as it is capable of altering entire seminatural communities
      through its vigorous spread. Control is essential if the conservation value of
      some communities, such as oak woodland and lowland heath, are to be successfully
      maintained. Commonly used interventions are herbicide application, herbicide
      application postcut, and cutting (manual or mechanical) alone. Various techniques
      have been developed to apply these interventions, but often retreatment of the
      area is required, increasing the cost of control. Here, we evaluate the
      effectiveness of some commonly used interventions for R. ponticum control using a
      systematic review methodology. Eleven studies provided data for statistical
      analysis. Meta-analyses of captured data show that postcut application of the
      herbicide Glyphosate or applying the herbicides Metsulfuron-methyl or Imazapyr
      (no cut) can effectively reduce a R. ponticum stand. There is insufficient
      available experimental evidence for effectiveness of any other intervention. The
      systematic review process has demonstrated the lack of replicated studies with
      controls or long-term monitoring and increases the call for more rigorous
      monitoring of all conservation management interventions. The quality of
      experimental evidence of the effectiveness of some interventions contrasts with
      the acceptance of their use through dissemination of experience. The collection
      and objective review of experience will require active collaboration of
      organizations concerned with R. ponticum control.

PMID- 16456629
TI  - Revegetation strategies for bauxite refinery residue: a case study of Alcan Gove
      in Northern Territory, Australia.
AB  - Alumina extraction from bauxite ore with strong alkali produces waste bauxite
      refinery residue consisting of residue sand and red mud. The amount and
      composition of refinery residue depend on the purity of the bauxite ore and
      extraction conditions, and differs between refineries. The refinery residue is
      usually stored in engineered disposal areas that eventually have to be
      revegetated. This is challenging because of the alkaline and sodic nature of the
      residue. At Alcan Gove's bauxite refinery in Gove, Northern Territory, Australia,
      research into revegetation of bauxite residue has been conducted since the mid
      1970s. In this review, we discuss approaches taken by Alcan Gove to achieve
      revegetation outcomes (soil capping of refinery residue) on wet-slurry disposal
      areas. Problems encountered in the past include poor drainage and water logging
      during the wet season, and salt scalding and capillary rise during the dry
      season. The amount of available water in the soil capping is the most important
      determinant of vegetation survival in the seasonally dry climate. Vegetation
      cover was found to prevent deterioration of the soil cover by minimising
      capillary rise of alkalinity from the refinery residue. The sodicity and
      alkalinity of the residue in old impoundments has diminished slightly over the 25
      years since it was deposited. However, development of a blocky structure in red
      mud, presumably due to desiccation, allows root penetration, thereby supplying
      additional water to salt and alkali-tolerant plant species. This has led to the
      establishment of an ecosystem that approaches a native woodland.

PMID- 16456630
TI  - Assessing the effects of nutrient management in an estuary experiencing climatic
      change: the Neuse River Estuary, North Carolina.
AB  - Eutrophication is a serious water quality problem in estuaries receiving
      increasing anthropogenic nutrient loads. Managers undertaking nutrient-reduction
      strategies aimed at controlling estuarine eutrophication are faced with the
      challenge that upstream freshwater segments often are phosphorus (P)-limited,
      whereas more saline downstream segments are nitrogen (N)-limited. Management also
      must consider climatic (hydrologic) variability, which affects nutrient delivery
      and processing. The interactive effects of selective nutrient input reductions
      and climatic perturbations were examined in the Neuse River Estuary (NRE), North
      Carolina, a shallow estuary with more than a 30-year history of accelerated
      nutrient loading and water quality decline. The NRE also has experienced a recent
      increase in Atlantic hurricanes and record flooding, which has affected hydrology
      and nutrient loadings. The authors examined the water quality consequences of
      selective nutrient (P but not N) reductions in the 1980s, followed by N
      reductions in the 1990s and an increase in hurricane frequency since the mid
      1990s. Selective P reductions decreased upstream phytoplankton blooms, but
      increased downstream phytoplankton biomass. Storms modified these trends. In
      particular, upstream annual N and P concentrations have decreased during the
      elevated hurricane period. Increased flushing and scouring from storms and
      flooding appear to have enhanced nutrient retention capabilities of the NRE
      watershed. From a management perspective, one cannot rely on largely
      unpredictable changes in storm frequency and intensity to negate anthropogenic
      nutrient enrichment and eutrophication. To control eutrophication along the
      hydrologically variable freshwater-marine continuum, N and P reductions should be
      applied adaptively to reflect point-source-dominated drought and non-point-source
      dominated flood conditions.

PMID- 16456631
TI  - Effectiveness of fish habitat compensation in Canada in achieving no net loss.
AB  - Fish habitat loss has been prevalent over the last century in Canada. To prevent
      further erosion of the resource base and ensure sustainable development,
      Fisheries and Oceans Canada enacted the habitat provisions of the Fisheries Act
      in 1976. In 1986, this was articulated by a policy that a "harmful alteration,
      disruption, or destruction to fish habitat" (HADD) cannot occur unless authorised
      with legally binding compensatory habitat to offset the HADD. Despite Canada's
      progressive conservation policies, the effectiveness of compensation habitat in
      replicating ecosystem function has never been tested on a national scale. The
      effectiveness of habitat compensation projects in achieving no net loss of
      habitat productivity (NNL) was evaluated at 16 sites across Canada. Periphyton
      biomass, invertebrate density, fish biomass, and riparian vegetation density were
      used as indicators of habitat productivity. Approximately 63% of projects
      resulted in net losses in habitat productivity. These projects were characterised
      by mean compensation ratios (area gain:area loss) of 0.7:1. Twenty-five percent
      of projects achieved NNL and 12% of projects achieved a net gain in habitat
      productivity. These projects were characterised by mean ratios of 1.1:1 and
      4.8:1, respectively. We demonstrated that artificially increasing ratios to 2:1
      was not sufficient to achieve NNL for all projects. The ability to replicate
      ecosystem function is clearly limited. Improvements in both compensation science
      and institutional approaches are recommended to achieve Canada's conservation
      goal.

PMID- 16456632
TI  - Compliance with Canada's Fisheries Act: a field audit of habitat compensation
      projects.
AB  - Loss of fish habitat in North America has occurred at an unprecedented rate
      through the last century. In response, the Canadian Parliament enacted the
      habitat provisions of the Fisheries Act. Under these provisions, a "harmful
      alteration, disruption, or destruction to fish habitat" (HADD) cannot occur
      unless authorised by Fisheries and Oceans Canada (DFO), with legally binding
      compensatory habitat to offset the HADD. The guiding principle to DFO's
      conservation goal is "no net loss of the productive capacity of fish habitats"
      (NNL). However, performance in achieving NNL has never been evaluated on a
      national scale. We investigated 52 habitat compensation projects across Canada to
      determine compliance with physical, biological, and chemical requirements of
      Section 35(2) Fisheries Act authorisations. Biological requirements had the
      lowest compliance (58%) and chemical requirements the highest (100%). Compliance
      with biological requirements differed among habitat categories and was poorest
      (19% compliance) in riparian habitats. Approximately 86% of authorisations had
      larger HADD and/or smaller compensation areas than authorised. The largest
      noncompliance in terms of habitat area occurred in riverine habitat in which
      HADDs were, on average, 343% larger than initially authorised. In total, 67% of
      compensation projects resulted in net losses of habitat area, 2% resulted in no
      net loss, and 31% achieved a net gain in habitat area. Interestingly, probable
      violations of the Fisheries Act were prevalent at half of the projects. Analyses
      indicated that the frequency of probable Fisheries Act violations differed among
      provinces. Habitat compensation to achieve NNL, as currently implemented in
      Canada, is at best only slowing the rate of habitat loss. In all likelihood,
      increasing the amount of authorised compensatory habitat in the absence of
      institutional changes will not reverse this trend. Improvements in monitoring and
      enforcement are necessary to move towards achieving Canada's conservation goals.

PMID- 16456633
TI  - Assessing the effects of alternative setback channel constraint scenarios
      employing a river meander migration model.
AB  - River channel migration and cutoff events within large river riparian corridors
      create heterogeneous and biologically diverse landscapes. However, channel
      stabilization (riprap and levees) impede the formation and maintenance of
      riparian areas. These impacts can be mitigated by setting channel constraints
      away from the channel. Using a meander migration model to measure land affected,
      we examined the relationship between setback distance and riparian and off
      channel aquatic habitat formation on a 28-km reach of the Sacramento River,
      California, USA. We simulated 100 years of channel migration and cutoff events
      using 11 setback scenarios: 1 with existing riprap and 10 assuming setback
      constraints from about 0.5 to 4 bankfull channel widths (bankfull width: 235 m)
      from the channel. The percentage of land reworked by the river in 100 years
      relative to current (riprap) conditions ranged from 172% for the 100-m constraint
      setback scenario to 790% for the 800-m scenario. Three basic patterns occur as
      the setback distance increases due to different migration and cutoff dynamics:
      complete restriction of cutoffs, partial restriction of cutoffs, and no
      restriction of cutoffs. Complete cutoff restriction occurred at distances less
      than about one bankfull channel width (235 m), and no cutoff restriction occurred
      at distances greater than about three bankfull widths (approximately 700 m).
      Managing for point bars alone allows the setbacks to be narrower than managing
      for cutoffs and aquatic habitat. Results suggest that site-specific "restriction
      of cutoff" thresholds can be identified to optimize habitat benefits versus cost
      of acquired land along rivers affected by migration processes.

PMID- 16456634
TI  - Socioeconomic factors affecting farmers' perceptions of land degradation and
      stonewall terraces in central Palestine.
AB  - Land degradation by soil erosion is a socioeconomic and environmental problem
      facing many developing countries. Application of stonewall terraces for soil
      moisture conservation is vital to reducing the environmental impacts of this
      phenomenon. To this end, a field plot experiment was conducted in the study area
      along with the use of a closed-ended questionnaire. The object of the experiment
      was to study the socioeconomic impacts of soil erosion on local farmers and their
      adoption of the stonewall terrace technique. The study showed a higher net profit
      in areas that had implemented terrace conservation practices than in areas that
      had not (i.e., 3.5 to 6 times higher net profit). Correlation analysis indicated
      that the farmers' perceptions, land ownership, and geomorphology were
      significantly related to the farmers' incentives and willingness to adopt
      terraces as soil conservation measures (P < 0.05), although the correlations were
      negative. Smallholder farmers (52% of the interviewed farmers) were involved in
      the sale of the agricultural land for urban uses, largely because of the high
      price and immediate returns offered. However, the associated land use changes
      warrant greater involvement of both the private and public sectors. This
      cooperation may be accomplished through the introduction of a long-term
      agricultural loan system and the development of proper legislation accompanied by
      a comprehensive and durable infrastructure and service system with the goal of
      reducing the negative impact of land use changes and encouraging sustainable use
      of resources.

PMID- 16456635
TI  - Urban environmental management in Shanghai: achievements, problems, and
      prospects.
AB  - This article critically reviews the evolution of urban environmental management
      in Shanghai since 1978. Established in a transitional post-socialist economy and
      shaped by a spectacular urban redevelopment process, the current environmental
      management framework of Shanghai has succeeded in mitigating major industrial
      pollution and improving urban amenities with unprecedented pace and magnitude.
      However, it generally failed to take social equity and environmental justice
      issues into consideration. Based on Haughton's models of sustainable urban
      development, this article proposes four priorities and five principles within the
      framework of a fair shares cities model for the future environmental management
      of Shanghai and briefly discusses their policy implications and implementation
      issues. The authors argue that Haughton's approach is relevant to Shanghai's case
      because the essence of his argument-the multidimensional equity principles-is the
      core of the concept of sustainable development.

PMID- 16456636
TI  - Long-term results after neoadjuvant radiochemotherapy for locally advanced
      resectable extraperitoneal rectal cancer.
AB  - PURPOSE: This study was designed to evaluate long-term outcome in locally
      advanced resectable extraperitoneal rectal cancer treated by preoperative
      radiochemotherapy. METHODS: Eighty-three consecutive patients who developed
      locally advanced resectable extraperitoneal rectal cancer underwent preoperative
      concomitant radiochemotherapy followed by surgery, including total mesorectal
      excision. RESULTS: Median follow-up was 108 (range, 10-169) months. The living
      patients underwent complete follow-up of, at least, nine years. Fourteen patients
      developed local recurrence. The time to detection was longer than two years in
      eight cases and longer than five years in four. Twenty-one patients developed
      metastases, 19 within the first five years from surgery. At the univariate
      analysis, clinical stage at presentation, lymph node involvement at clinical
      restaging after neoadjuvant therapy, and pT and pN stage were found positively
      correlated to the incidence of metastases. At the multivariate analysis, the only
      factors which confirmed a positive correlation were pT stage and pN stage. The
      actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4
      percent, respectively. The same figures for cancer-related survival were 77.9,
      70, and 65.8 percent. At the univariate analysis, factors directly correlated
      with worse survival were: TNM stage at clinical restaging after neoadjuvant
      therapy (in particular lymph node involvement) pTNM, pT, and pN. At the
      multivariate analysis the only factors that confirmed a correlation with worse
      survival were pTNM, pT, and pN. CONCLUSIONS: Long- term follow-up allows to
      individuate 28 percent of all local relapses after the first five years from
      surgery. Postoperative stage is highly predictive of prognosis.

PMID- 16456637
TI  - Comparison of glycerine trinitrate and botulinum toxin-a for the treatment of
      chronic anal fissure: long-term results.
AB  - PURPOSE: This study was designed to compare the efficacy of two different
      "chemical sphincterotomies" for chronic anal fissure. METHODS: From January to
      December 2001, 30 consecutive patients (17 males; mean age, 41.8 years) with
      chronic posterior anal fissure were enrolled. The patients were randomly assigned
      to receive 0.2 percent glycerine trinitrate ointment applied three times daily at
      the anal margin for eight weeks (Group A) or 20 units Botulinum toxin A injection
      into the internal anal sphincter on each side of the anterior midline (Group B).
      The patients were reviewed at 15 days, 1, 3, 6, 12, and every other 12 months.
      Follow-up ranged between 36 and 46 months. Patients in either group who failed to
      improve were referred for surgical treatment. RESULTS: Twelve patients in Group A
      and 11 in Group B had improvement or relief from symptoms at the first visit. The
      fissure was healed in ten patients in Group A and in eight in Group B within
      three months (66.7 and 57.1 percent). Recurrence of the fissure occurred in five
      patients in each group during the follow-up. The healing rate at three years was
      40 and 33.3 percent for Group A and B, respectively. No patients in either group
      reported serious adverse effects; however, three patients in Group A (20 percent)
      had transient headache. None had fecal incontinence. CONCLUSION: Both treatments
      may be considered as first-line treatment even if less effective than surgery.

PMID- 16456638
TI  - Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer:
      evidence from randomized trials.
AB  - PURPOSE: The main treatment for resectable rectal cancer T2-T4 N0-N2 M0 is
      surgery. The benefit of preoperative or postoperative radiation therapy can be
      analyzed in terms of improvement of local control, sphincter preservation, and
      survival weighted against increased toxicity. METHODS: Only randomized trials can
      provide strong evidence of a positive cost-benefit ratio of such combined
      approach. The most recent trials were reviewed. RESULTS: Three randomized trials,
      including the latest German CAO-ARO trial, have demonstrated the superiority of
      preoperative radiotherapy with or without chemotherapy (vs. postoperative) in
      terms of local control and toxicity. The Ducth TME trial showed that even with
      modern standard surgery, preoperative radiotherapy improved local control.
      Preoperative irradiation using a high dose in a small volume and a long interval
      before surgery may improve sphincter preservation (Lyon trials). Concurrent
      chemoradiation (FFCD 9203, EORTC 22921, did not significantly improve sphincter
      preservation or survival but significantly reduced the local recurrence rate.
      CONCLUSIONS: In 2005 examination of randomized trials provides evidence for the
      benefit of preoperative chemoradiation in improving local control and probably
      sphincter preservation in rectal cancer. Randomized trials should be designed to
      further demonstrate improved sphincter preservation and to increase survival
      using adjuvant medical treatments.

PMID- 16456639
TI  - Experimental and numerical smoke carcinogen deposition in a multi-generation
      human replica tracheobronchial model.
AB  - A better understanding of submicron particle deposition in the respiratory tract
      is needed to study the health effects caused by carcinogenic particles. Recent
      studies indicate that random diffusion is not sufficient to describe the motion
      of these particles in complex geometries, rendering conventional models
      inaccurate. A solid replica of excised human lung segments was used to create
      digital and hollow models of the tracheobronchial region to investigate
      deposition of mainstream (MS) and sidestream (SS) cigarette smoke particles.
      Particle sizes for the carcinogen Benzo(a)pyrene (BaP) in SS smoke, and total
      particulate matter (UVPM) in SS and MS smoke were measured and used to compare
      the simulation to experimental data. Excellent agreement was found between
      predicted and measured results. Random diffusion was not found to be significant
      for submicron particles indicating that particles were instead transported to the
      airway wall by convective diffusion. BaP in SS smoke was an average 0.3 mum
      compared to 0.36 mum for UVPM in SS smoke. The trends in both experimental and
      numerical results indicated that the BaP in SS smoke deposits at a slightly
      higher efficiency than the UVPM, indicating that carcinogen-specific deposition,
      rather than total particulate matter should be considered when investigating
      health effects.

PMID- 16456640
TI  - Nanoscale intracellular organization and functional architecture mediating
      cellular behavior.
AB  - Cells function based on a complex set of interactions that control pathways
      resulting in ultimate cell fates including proliferation, differentiation, and
      apoptosis. The inter-workings of this immensely dense network of intracellular
      molecules are influenced by more than random protein and nucleic acid
      distribution where their interactions culminate in distinct cellular function. By
      probing the design of these biological systems from an engineering perspective,
      researchers can gain great insight that will aid in building and utilizing
      systems that are on this size scale where traditional large-scale rules may fail
      to apply. The organized interaction and gradient distribution in intracellular
      space imply a structural architecture that modulates cellular processes by
      influencing biochemical interactions including transport and binding-reactions.
      One significant structure that plays a role in this modulation is the cell
      cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating
      functional structure in influencing cell processes and we describe technology
      useful for probing this structure. We explain the nanometer scale science of
      cytoskeletal structure with respect to intracellular organization,
      mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as
      well as nano- and microtechnologies that are applicable for experimental studies
      of the cytoskeleton. This biological architecture of the cytoskeleton influences
      molecular, cellular, and physiological processes through structured multimodular
      and hierarchical principles centered on these functional filaments. Through
      investigating these organic systems that have evolved over billions of years,
      understanding in biology, engineering, and nanometer-scaled science will be
      advanced.

PMID- 16456641
TI  - Satisfaction with treatment among patients with depressive and bipolar disorders.
AB  - BACKGROUND: Patients' satisfaction with care may be an important factor in
      relation to adherence to treatment and continued psychiatric care. Few studies
      have focused on satisfaction in patients with depressive and bipolar disorders.
      METHOD: A comprehensive multidimensional questionnaire scale, the Verona Service
      Satisfaction Scale-Affective, was mailed to a large population of patients with
      depressive or bipolar disorders representative of outpatients treated at their
      first contact to hospital settings in Denmark. RESULTS: Among the 1,005
      recipients, 49.9% responded to the letter. Overall, patients were satisfied with
      the help provided, but satisfaction with the professionals' contact to relatives
      was low. Younger patients (age below 40 years) were consistently more
      dissatisfied with care especially with the efficacy of treatment, professionals'
      skills and behaviour and the information given. There was no difference in
      satisfaction between genders or between patients with depressive disorder and
      patients with bipolar disorder. CONCLUSION: There is a need to strengthen
      outpatient treatment for patients discharged from a psychiatric hospital
      diagnosed of having affective disorders, focusing more on information and
      psychoeducation for patients and relatives.

PMID- 16456643
TI  - Orthographically influenced abstract phonological representation: evidence from
      non-rhotic speakers.
AB  - It is typically assumed that when orthography is translated silently into
      phonology (i.e., when reading silently), the phonological representation is
      equivalent to the spoken form or, at least, the surface phonemic form. The
      research presented here demonstrates that the phonological representation is
      likely to be more abstract than this, and is orthographically influenced. For
      example, the claim is made that the word "corn" has an underlying /r/ in its
      phonological representation, even in non-rhotic dialects. The evidence comes from
      difficulties observed in judgements about the homophony with a target word of a
      pseudohomophone whose phonology does not match the putative abstract
      representation of that word. For example, it is hard to say that the
      pseudohomophone "cawn" is homophonic with "corn". The conclusion that orthography
      can shape phonological representation is antithetical to both computational
      models of the conversion of print to sound and linguistic accounts of phonology.

PMID- 16456642
TI  - [Interstitial pulmonary diseases].
AB  - Interstitial pneumonia is a rare disease, posing a diagnostic challenge to
      pneumologists, pediatricians, radiologists and pathologists. Only by the combined
      efforts of the European Respiratory Society (ERS) and the American Thoracic
      Society (ATS) has has been possible to standardize the formerly different
      European and Northern American nomenclature of interstitial lung diseases
      (alveolitis versus interstitial pneumonia) in adults and to clearly and
      unambiguously define the diagnostic criteria. The ATS/ERS classification of 2002
      comprises seven entities: usual interstitial pneumonia (UIP), non-specific
      interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP),
      respiratory bronchiolitis-associated interstitial lung disease (RB-ILD),
      cryptogenic organizing pneumonia (COP), lymphocyte interstitial pneumonia (LIP),
      and acute interstitial pneumonia (AIP). Using the ATS/ERS classification of
      interstitial pulmonary diseases in premature infants, infants and children is
      problematic, since UIP, RB-ILD and AIP do not occur at this age. Although infants
      with severe respiratory insufficiency may sometimes show morphological features
      similar to DIP or NSIP, this entity should rather be classified as chronic
      pneumonitis of infancy (CPI) because of differences in etiology, pathogenesis and
      prognostic outcome.

PMID- 16456644
TI  - Deep, prolonged torpor by pregnant, free-ranging bats.
AB  - Many mammals save energy during food shortage or harsh weather using controlled
      reductions in body temperature and metabolism called torpor. However, torpor
      slows offspring growth, and reproductive individuals are thought to avoid using
      it because of reduced fitness resulting from delayed offspring development. We
      tested this hypothesis by investigating torpor during reproduction in hoary bats
      (Lasiurus cinereus, Vespertilionidae) in southern Canada. We recorded deep,
      prolonged torpor bouts, which meet the definition for hibernation, by pregnant
      females. Prolonged torpor occurred during spring storms. When conditions improved
      females aroused and gave birth within several days. Our observations imply a
      fitness advantage of torpor in addition to energy conservation because reduced
      foetal growth rate could delay parturition until conditions are more favourable
      for lactation and neonatal survival.

PMID- 16456645
TI  - Swapped green algal promoters: aphVIII-based gene constructs with Chlamydomonas
      flanking sequences work as dominant selectable markers in Volvox and vice versa.
AB  - Production of transgenic organisms is a well-established, versatile course of
      action in molecular biology. Genetic engineering often requires heterologous,
      dominant antibiotic resistance genes that have been used as selectable markers in
      many species. However, as heterologous 5' and 3' flanking sequences often result
      in very low expression rates, endogenous flanking sequences, especially
      promoters, are mostly required and are easily obtained in model organisms, but it
      is much more complicated and time-consuming to get appropriate sequences from
      less common organisms. In this paper, we show that aminoglycoside 3'
      phosphotransferase gene (aphVIII) based constructs with 3' and 5' untranslated
      flanking sequences (including promoters) from the multicellular green alga Volvox
      work in the unicellular green alga Chlamydomonas and flanking sequences from
      Chlamydomonas work in Volvox, at least if a low expression rate is compensated by
      an enforced high gene dosage. This strategy might be useful for all investigators
      that intend to transform species in which genomic sequences are not available,
      but sequences from related organisms exist.

PMID- 16456646
TI  - Expression profile of a PAL gene from Astragalus membranaceus var. Mongholicus
      and its crucial role in flux into flavonoid biosynthesis.
AB  - An important traditional Chinese medicine herb, Astragalus membranaceus var.
      Mongholicus, whose dried root is known as Radix astragali ("Huangqi" in Chinese),
      has high flavonoid content as an essential active constituent. Phenylalanine
      ammonia-lyase (PAL, EC 4.3.1.5) catalyzes the first and also a rate-limiting step
      in phenylpropanoid pathway, which supplies precursors for a variety of secondary
      metabolites including flavonoids. A PAL gene, designated AmPAL1 (GenBank
      accession no. AY986506), was isolated from A. membranaceus var. Mongholicus with
      a full-length cDNA of 2562 nucleotides and an open reading frame of 2154 bp.
      Northern blot analysis revealed that AmPAL1 expressed universally in different
      organs, and its expression was markedly induced by UV irradiation, mechanical
      wounding, and white light irradiation on etiolated seedlings, with some
      distinctive responsive properties. Content of a typical flavonoid, quercetin, in
      A. membranaceus var. Mongholicus of different ages correlated with PAL enzymatic
      activity. Transgenic tobacco plants harboring AmPAL1 under the control of the
      CaMV35S promoter showed significantly increased PAL activity and correlatively
      increased quercetin content than those in non-transformed plants. These results
      indicate that PAL is maybe a key point for flux into flavonoid biosynthesis in
      the genetic control of secondary metabolism in A. membranaceus var. Mongholicus.

PMID- 16456647
TI  - Genetic and biochemical analysis of Hypericum perforatum L. plants regenerated
      after cryopreservation.
AB  - Shoot-tips from in vitro cultured Hypericum perforatum L. genotypes were
      subjected to assessments of developmental competence, genetic stability, and
      biosynthetic ability to identify critical points during cryopreservation.
      Survival rate, chromosome number stability, alteration in VNTR sequences and
      hypericin content were evaluated, in plants after pre-culture, and two subsequent
      cryogenic steps (cryoprotection and cooling) and those recovered from
      cryopreserved meristems. Pre-culture and cryoprotection treatments, did not
      reveal any significant differences, in these studied characteristics. Genetic
      stability was assessed by chromosome counts and analysis of variability in the
      VNTR sequences. No changes in chromosome number were detected in comparison with
      the untreated control but minor alterations were revealed in non-coding
      sequences. The content of hypericin after the recovery of cryopreserved meristems
      remained comparable with the unfrozen control. The controlled rate freezing
      technique used for cryopreservation was relevant for restoration of genetic and
      biochemical stability in Hypericum perforatum L. shoot-tips.

PMID- 16456648
TI  - Characterisation of basal resistance (BR) by expression patterns of newly
      isolated representative genes in tobacco.
AB  - Increasing evidence indicates that plants, like animals, use basal resistance
      (BR), a component of the innate immune system, to defend themselves against
      foreign organisms. Contrary to the hypersensitive reaction (HR)-type cell death,
      recognition in the case of BR is unspecific, as intruders are recognised based on
      their common molecular patterns. Induction of BR is not associated with visible
      symptoms, in contrast to the HR-type cell death. To analyse the early events of
      BR in tobacco plants we have carried out a subtractive hybridisation between
      leaves treated with the HR-negative mutant strain Pseudomonas syringae pv.
      syringae 61 hrcC and non-treated control leaves. Random sequencing from the 304
      EBR clones yielded 20 unique EST-s. Real-time PCR has proved that 8 out of 10
      clones are activated during BR. Six of these EST-s were further analyzed. Gene
      expression patterns in a time course showed early peaks of most selected genes at
      3-12 h after inoculation (hpi), which coincided with the development-time of BR.
      Upon treatments with different types of bacteria we found that incompatible
      pathogens, their hrp mutants, as well as non-pathogens induce high levels of
      expression while virulent pathogens induce only a limited gene-expression. Plant
      signal molecules like salicylic acid, methyl jasmonate, ethylene and spermine,
      known to be involved in plant defense were not able to induce the investigated
      genes, therefore, an unknown signalling mechanism is expected to operate in BR.
      In summary, we have identified representative genes associated with BR and have
      established important features of BR by analysing gene-expression patterns.

PMID- 16456650
TI  - Estimation of radiation exposure in low-dose multislice computed tomography of
      the heart and comparison with a calculation program.
AB  - The purpose of this study was to evaluate the achievable organ dose savings in
      low-dose multislice computed tomography (MSCT) of the heart using different tube
      voltages (80 kVp, 100 kVp, 120 kVp) and compare it with calculated values. A
      female Alderson-Rando phantom was equipped with thermoluminescent dosimeters
      (TLDs) in five different positions to assess the mean doses within representative
      organs (thyroid gland, thymus, oesophagus, pancreas, liver). Radiation exposure
      was performed on a 16-row MSCT scanner with six different routine scan protocols:
      a 120-kV and a 100-kV CT angiography (CTA) protocol with the same collimation,
      two 120-kV Ca-scoring (CS) protocols with different collimations and two 80-kV CS
      protocols with the same collimation as the 120-kV CS protocols. Each scan
      protocol was repeated five times. The measured dose values for the organs were
      compared with the values calculated by a commercially available computer program.
      Directly irradiated organs, such as the esophagus, received doses of 34.7 mSv
      (CTA 16x0.75 120 kVp), 21.9 mSv (CTA 16x0.75 100 kVp) and 4.96 mSv (CS score
      12x1.5 80 kVp), the thyroid as an organ receiving only scattered radiation
      collected organ doses of 2.98 mSv (CTA 16x0.75 120 kVp), 1.97 mSv (CTA 16x0.75
      100 kVp) and 0.58 mSv (CS score 12x1.5 80 kVp). The measured relative organ dose
      reductions from standard to low-kV protocols ranged from 30.9% to 55.9% and were
      statistically significant (P<0.05). The comparison with the calculated organ
      doses showed that the calculation program can predict the relative dose reduction
      of cardiac low photon-energy protocols precisely.

PMID- 16456649
TI  - Expression of the antimicrobial peptides in plants to control phytopathogenic
      bacteria and fungi.
AB  - Three antimicrobial peptides exhibiting in vitro antifungal activity were
      expressed in Arabidopsis to compare their in planta activity. Beta-Purothionin,
      cecropin B, and phor21 were expressed under an endogenous promoter with moderate
      level activity and excreted extracellularly. Expression of beta-purothionin
      rendered the greatest antibacterial and antifungal resistance while cecropin B
      enhanced only antibacterial activity and phor21 did not improve antimicrobial
      resistance. The transgenic beta-purothionin arrested fungal growth on leaf
      surfaces and infection of stomata. Leaf extracts from plants producing beta
      purothionin and cecropin B displayed membrane permeabilizing activity. The in
      planta antimicrobial activity of the tested peptides was consistent with
      previously reported in vitro experiments. The expression strategy allowed
      enhanced antifungal resistance without high-level transgene expression.

PMID- 16456651
TI  - Mutidetector-row CT and quantitative gated SPECT for the assessment of left
      ventricular function in small hearts: the cardiac physical phantom study using a
      combined SPECT/CT system.
AB  - The aim of this study was to compare results of left ventricular (LV) function
      obtained by quantitative gated single-photon emission tomography (QGS) and
      multidetector-row spiral computed tomography (MDCT) with reference parameters
      using an electrocardiogram-gated cardiac physical phantom. The phantom study was
      performed using a combined SPECT/CT system. Flexible membranes formed the inner
      and outer walls of the simulated LV. The stroke volume was adjusted (45 mL or 58
      mL) and the fixed 42-mL end-systolic volume (ESV) produced two different volume
      combinations. The LV function parameters were estimated by means of MDCT and QGS.
      Differences in true and measured volumes were compared among CT with a
      reconstructed image thickness of 2.5 mm and 5.0 mm and QGS volumetric values.
      Each scan was repeated three-times. The estimation of LV volumes using both QGS
      and MDCT analyses were reproducible very well. QGS overestimated ejection
      fraction (EF) by approximately 20%; MDCT volumetry overestimated EF by
      approximately 5% in each volume setting. The differences in true and measured
      values for EF and ESV obtained with QGS were significantly greater than obtained
      with MDCT. CONCLUSION: MDCT provides a reliable estimation of functional LV
      parameters, whereas QGS tends to significantly overestimate the EF in small
      hearts.

PMID- 16456653
TI  - Hepatoblastoma: why so many low-birth-weight infants?

PMID- 16456652
TI  - Localization of putative stem cells and four cell populations with different
      differentiation degree in mouse mammary anlagen.
AB  - The precise localization of putative stem cells and other cells within the
      embryonic mammary gland would help to elucidate the molecular pathways that
      govern normal mammary development. The ultrastructural appearances and the
      antigen of Sca-1 were considered together as putative stem cell markers, and the
      antigens of cytokeratin, CD10, Muc-1 and CD34 as differentiation markers.
      Electron microscopy was performed to reveal the ultrastructure of cells in
      different site of the mammary anlagen. An immunofluorescence system was used to
      reveal the whole structure profile of the mammary anlagen using the anti
      cytokeratin antibody to localize specific types of cell populations such as Sca
      1, CD10, Muc-1 and CD34 positive cells within the anlagen, which distribute near
      the inside edge, distribute uniformly, distribute in the central region and
      distribute in the site of mesenchyme around the neck of the anlagen,
      respectively. We also observed under electron microscope that some pale cells
      like putative stem cells reported by prevenient scholars, which are mainly
      distributed in the Sca-1(+) cell population near the inside edge of the anlagen,
      have pale-stained nucleoplasm and cytoplasm, sparse organelles clustered close to
      their nucleus and have a lack of rough endoplasmic reticulums and cell
      polarization. The results indicate that the putative stem cells are localized
      near the edge of the mammary anlagen; the cell populations with different
      differentiation degree were localized in the central part and around the edge
      within the anlagen.

PMID- 16456654
TI  - [Chronic diseases after gastrointestinal surgery].
AB  - Gastrointestinal surgery may not only lead to early postoperative complications
      but also chronic consequences. These have therapeutic implications for affected
      patients. The kind and extent of surgical intervention determines the spectrum of
      postsurgical phenomena which may occur. These chronic consequences are due to
      changes in gastrointestinal anatomy, the synchronization of digestive processes,
      or the ability to digest and absorb food. In case of transplantation surgery,
      adverse effects of immunosuppression have to be considered. Sometimes, chronic
      consequences of surgical procedures are difficult to recognize. The knowledge of
      typical problems associated with gastrointestinal surgery is necessary to enable
      early and timely diagnosis and treatment. Some negative effects can be avoided by
      early therapeutic interventions. This article summarizes typical chronic
      consequences of gastrointestinal surgery.

PMID- 16456655
TI  - Hybrid lethality in interspecific hybrids between Nicotiana tabacum and N.
      suaveolens: evidence that the Q chromosome causes hybrid lethality based on Q
      chromosome-specific DNA markers.
AB  - Hybrid seedlings from the cross Nicotiana tabacum x N. suaveolens express
      lethality at 28 degrees C. We carried out a cross between monosomic lines of N.
      tabacum lacking the Q chromosome and N. suaveolens by test-tube pollination and
      ovule culture at 28 degrees C. To suppress hybrid lethality, hybrid seedlings
      obtained were transferred to 36 degrees C immediately after germination and
      cultured. We determined whether Q-chromosome-specific DNA markers were detected
      among hybrid seedlings. When hybrid seedlings cultured at 36 degrees C were
      transferred to 28 degrees C, hybrid seedlings in which Q-chromosome-specific DNA
      markers were detected expressed hybrid lethality, while hybrid seedlings in which
      Q-chromosome-specific DNA markers were not detected did not express hybrid
      lethality. From these results, we concluded that the presence of the Q chromosome
      of N. tabacum is related to hybrid lethality observed in crosses between N.
      tabacum and N. suaveolens. This is the first report that clearly demonstrates the
      relationship between a certain chromosome and hybrid lethality in the genus
      Nicotiana using chromosome-specific DNA markers. Additionally, we confirmed that
      the Q chromosome belongs to the S subgenome because Q-chromosome-specific DNA
      markers were detected only in N. sylvestris.

PMID- 16456656
TI  - Genomic analysis and marker development for the Tsn1 locus in wheat using bin
      mapped ESTs and flanking BAC contigs.
AB  - The wheat Tsn1 gene confers sensitivity to the host-selective toxin Ptr ToxA
      produced by the tan spot fungus (Pyrenophora tritici-repentis). The long-term
      goal of this research is to isolate Tsn1 using a positional cloning approach.
      Here, we evaluated 54 ESTs (expressed sequence tags) physically mapped to
      deletion bin 5BL 0.75-0.76, which is a gene-rich region containing Tsn1. Twenty
      three EST loci were mapped as either PCR-based single-stranded conformational
      polymorphism or RFLP markers in a low-resolution wheat population. The genetic
      map corresponding to the 5BL 0.75-0.76 deletion bin spans 18.5 cM and contains 37
      markers for a density of 2 markers/cM. The EST-based genetic map will be useful
      for tagging other genes, establishing colinearity with rice, and anchoring
      sequence ready BAC contigs of the 5BL 0.75-0.76 deletion bin. High-resolution
      mapping showed that EST-derived markers together with previously developed AFLP
      derived markers delineated Tsn1 to a 0.8 cM interval. Flanking markers were used
      to screen the Langdon durum BAC library and contigs of 205 and 228 kb flanking
      Tsn1 were assembled, sequenced, and anchored to the genetic map. Recombination
      frequency averaged 760 kb/cM across the 228 kb contig, but no recombination was
      observed across the 205 kb contig resulting in an expected recombination
      frequency of more than 10 Mb/cM. Therefore, chromosome walking within the Tsn1
      region may be difficult. However, the sequenced BACs allowed the identification
      of one microsatellite in each contig for which markers were developed and shown
      to be highly suitable for marker-assisted selection of Tsn1.

PMID- 16456658
TI  - Intracellular recording from a spider vibration receptor.
AB  - The present study introduces a new preparation of a spider vibration receptor
      that allows intracellular recording of responses to natural mechanical or
      electrical stimulation of the associated mechanoreceptor cells. The spider
      vibration receptor is a lyriform slit sense organ made up of 21 cuticular slits
      located on the distal end of the metatarsus of each walking leg. The organ is
      stimulated when the tarsus receives substrate vibrations, which it transmits to
      the organ's cuticular structures, reducing the displacement to about one tenth
      due to geometrical reasons. Current clamp recording was used to record action
      potentials generated by electrical or mechanical stimuli. Square pulse
      stimulation identified two groups of sensory cells, the first being single-spike
      cells which generated only one or two action potentials and the second being
      multi-spike cells which produced bursts of action potentials. When the more
      natural mechanical sinusoidal stimulation was applied, differences in adaptation
      rate between the two cell types remained. In agreement with prior extracellular
      recordings, both cell types showed a decrease in the threshold tarsus deflection
      with increasing stimulus frequency. Off-responses to mechanical stimuli have also
      been seen in the metatarsal organ for the first time.

PMID- 16456657
TI  - A behavioural and functional neuroimaging investigation into the effects of
      nicotine on sensorimotor gating in healthy subjects and persons with
      schizophrenia.
AB  - RATIONALE: Schizophrenia patients display an excessive rate of smoking compared
      to the general population. Nicotine increases acoustic prepulse inhibition (PPI)
      in animals as well as healthy humans, suggesting that smoking may provide a way
      of restoring deficient sensorimotor gating in schizophrenia. No previous study
      has examined the neural mechanisms of the effect of nicotine on PPI in humans.
      OBJECTIVES: To investigate whether nicotine enhances tactile PPI in healthy
      subjects and patients with schizophrenia employing a double-blind, placebo
      controlled, cross-over design and, if so, what are the neural correlates of
      nicotine-induced modulation of PPI. MATERIALS AND METHODS: In experiment 1, 12
      healthy smokers, 12 healthy non-smokers and nine smoking schizophrenia patients
      underwent testing for tactile PPI on two occasions, 14 days apart, once after
      receiving (subcutaneously) 12 microg/kg body weight of nicotine and once after
      receiving saline (placebo). In experiment 2, six healthy subjects and five
      schizophrenia patients of the original sample (all male smokers) underwent
      functional magnetic resonance imaging (fMRI) under the same drug conditions and
      the same tactile PPI paradigm as in experiment 1. RESULTS: Nicotine enhanced PPI
      in both groups. A comparison of patterns of brain activation on nicotine vs
      placebo conditions showed increased activation of limbic regions and striatum in
      both groups after nicotine administration. Subsequent correlational analyses
      demonstrated that the PPI-enhancing effect of nicotine was related to increased
      hippocampal activity in both groups. CONCLUSIONS: Nicotine enhances tactile PPI
      in both healthy and schizophrenia groups. Our preliminary fMRI findings reveal
      that this effect is modulated by increased limbic activity.

PMID- 16456660
TI  - Salvage of proximal tibial malunion or nonunion with the use of angled blade
      plate.
AB  - INTRODUCTION: Single buttress plating laterally was sometimes performed by a few
      orthopedists to treat complex tibial plateau fractures with medial compartment
      involvement. However, we might encounter cases with medial compartment collapse
      due to such treatment. The causes of failure, the technique of the revision
      surgery, and the methods of prevention were investigated retrospectively. The
      purpose of this study was to report our clinical results of a retrospectively
      followed series of patients treated with blade plate fixation for proximal tibial
      metaphyseal nonunions and malunions which were treated with unilateral plating.
      MATERIALS AND METHODS: Twenty-eight patients with failed treatment of complex
      tibial plateau fractures due to single buttress plating laterally underwent the
      revision surgeries. Removal of the buttress plate, proximal tibial corrective
      osteotomy, and insertion of an angled blade plate medially were performed.
      Postoperatively, exercise of the range of motion of the knee was encouraged as
      early as possible. RESULTS: Twenty-five patients were followed-up for a median of
      4.8 years (range, 1.2-6.8), and all fractures healed at a median of 4.0 months
      (range, 3.0-6.0). The proximal medial tibial angle (PMTA) was corrected to the
      acceptable range (80-99 degrees ) in all 25 patients (P<0.001) and knee function
      improved in 22 out of 25 patients (P<0.001). CONCLUSION: For clinical and
      biomechanical considerations, single buttress plating laterally was unsuitable
      for complex tibial plateau fractures with medial compartment involvement due to
      relatively huge compressive loads on the medial compartment. The stability
      provided by a few screws of the buttress plate laterally was normally
      insufficient. An angled blade plate could be a useful armament in the management
      of metaphyseal nonunion and malunions of the proximal tibia. Its better
      stabilization could normally provide a high success rate.

PMID- 16456659
TI  - The immediate and long-term outcomes of newborns with congenital diaphragmatic
      hernia.
AB  - In spite of the innovations in the management of newborns with congenital
      diaphragmatic hernia (CDH) presenting with respiratory distress at birth,
      mortality and ongoing morbidity still remain high. This is a retrospective
      analysis of newborns with CDH to determine the immediate and long-term outcomes
      among survivors. Medical records of newborns with CDH and respiratory distress at
      birth between January 1993 and March 2002 were reviewed retrospectively. There
      were 45 newborns, 29 males and 16 females. Eleven newborns (24%) died during the
      period of preoperative stabilization, 9 from pulmonary hypoplasia and 2 with
      complex anomalies who were not resuscitated. Surgery was performed in 34 newborns
      (76%). Three died postoperatively from severe pulmonary hypoplasia and pulmonary
      hypertension. Eleven newborns (24%) had sepsis from coagulative-negative
      staphylococci. Thirty-one of 43 newborns (72%) with isolated CDH were discharged
      home. Twenty-seven of 31 survivors (87%) had adverse long-term outcome and 2 late
      deaths were from pulmonary complications. Twenty-nine of 43 newborns (67%) with
      isolated CDH survived. The principal determinant of survival was pulmonary
      hypoplasia. Eighty-seven percent of survivors have associated morbidity including
      ongoing pulmonary, nutritional and neuro-developmental problems. Nevertheless
      preoperative stabilization and delayed surgery have been a satisfactory mode of
      management.

PMID- 16456661
TI  - Glenohumeral interposition of a torn rotator cuff in a young motorcyclist.
AB  - This report describes the rare case of a traumatic rotator cuff tear in a young
      patient which led to a pseudo-paralyzed shoulder by interposition of the tendon
      stump into the glenohumeral joint. The patient underwent an open rotator cuff
      repair and regained an almost normal shoulder function after 12 weeks. A review
      of the literature is presented.

PMID- 16456662
TI  - Assessment of bone quality in the proximal humerus by measurement of the
      contralateral site: a cadaveric analyze.
AB  - INTRODUCTION: The presence of osteoporosis decreases the success of
      osteosynthesis, especially in the proximal humerus. Estimation of the bone
      mineral density (BMD) at the fracture site could aid in the decision making for
      surgical treatment and potential implant choice with regard to the individual
      bone properties. BMD measurement at a fracture site is prone to inaccuracies and
      alternative measurement sites need to be identified. In the case of a proximal
      humerus fracture, promising alternative measurement sites are at the same
      contralateral or at a different ipsilateral location. The aim of this study was
      to determine if the BMD for the humeral head can be predicted by BMD measurements
      from the ipsilateral distal humerus or the contralateral proximal humerus.
      MATERIAL AND METHODS: Cancellous BMD values were obtained from 88 paired human
      cadaver humeri (age 75.8+/-13.5 years) at the humeral head and at the distal
      metaphyseal area by pQCT. Correlations between BMD values of the ipsi- and
      contralateral sites were computed. RESULTS: Correlations between proximal and
      distal BMD values within one bone were moderate for both left (R2=0.37) and right
      humeri (R2=0.40). BMD comparison between left and right humeri revealed high
      correlations for both the distal (R2=0.90) and the proximal humerus (R2=0.74)
      (all P<0.01). Elderly specimen (>or=70 years) showed better intersite
      correlations between all regions than younger specimen (<70 years). CONCLUSION:
      High correlations between contralateral BMD values may be the result of similar
      biomechanical loading conditions. Although a relationship between proximal and
      distal bone quality of the same bone was found, the moderate coefficient suggests
      that ipsilateral measurements do not provide a good prediction of humeral head
      BMD. Bone quality at the humeral head is best predicted by BMD measurements at
      the contralateral location rather than the ipsilateral distal site.

PMID- 16456663
TI  - The migration of a BioScrew as a differential diagnosis of knee pain, locking
      after ACL reconstruction: a report of two cases.
AB  - INTRODUCTION: Problems with the initial fixation strength and widening of the
      femoral and tibial canal after ACL reconstruction using a triple or quadruple
      semitendinosus autograft have led to the introduction of the so-called Hybrid
      fixation with the additional use of interference screws. Pain and intraarticular
      migration have been reported with metal interference screws requiring implant
      removal (Am J Knee Surg 11:32-34, 2000, Arthroscopy 11:289-291, 1995) but not yet
      with bioabsorbable screws. MATERIALS AND METHODS: We report on two cases were the
      intraarticular position of a bioabsorbable interference screw possibly due to
      migration in the early postoperative period lead to symptoms, the need for
      further surgery, and implant removal. RESULTS: A preoperative MRI revealed the
      diagnosis. After removal of the tibial interference screw both knees were
      settling down, albeit with residual instability and only a moderate clinical
      result. DISCUSSION: Despite the attractiveness of bioabsorbable screws due to the
      very fact that they are being reabsorbed over time, there is a slight risk of
      migration in the first month after the operation. In any suspicious case an MRI
      will easily clarify the diagnosis.

PMID- 16456664
TI  - Increased production of vascular endothelial growth factor in the lesions of
      atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by
      severe itching, erythema and edema resistant to anti-histamine therapy. Vascular
      endothelial growth factor (VEGF) is a potent agent that causes hyperpermeability
      of blood vessels and endothelial cell proliferation, and might be involved in the
      persisting erythema and edema in AD. In this study, we used extraction of stratum
      corneum with physiological saline to detect VEGF produced in the lesions of AD.
      Biological activity of VEGF was assayed by proliferation of cultured human
      umbilical vein endothelial cells in vitro. As a result, we found that the amount
      of VEGF produced in lesional scales was approximately 25 times higher than that
      in normal stratum corneum. Moreover, VEGF 121 isoform that exclusively induces
      hyperpermeability of blood vessels was a predominant component in the lesional
      scales suggesting that this factor plays an important role in the persisting
      erythema and edema in the AD lesions.

PMID- 16456665
TI  - Coexistence of PSP and MSA: a case report and review of the literature.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy
      characterized by Parkinsonism, vertical gaze palsy, and early falls. The
      neuropathology is characterized by neurofibrillary tangles, tufted astrocytes,
      and coiled bodies, but some brains show other pathologic processes. To
      investigate the frequency of alpha-synuclein pathology in PSP with
      immunohistochemistry and to report the clinical and pathological features of a
      case of PSP with concomitant Multiple system atrophy (MSA) (PSP/MSA), 290 cases
      of PSP were screened for alpha-synuclein pathology with immunohistochemistry.
      Double-labeling immunohistochemistry was performed on a case of PSP/MSA. Among
      the PSP cases screened for alpha-synuclein pathology, a single case of PSP/MSA
      was detected. The patient was an 86-year-old woman with clinical features
      consistent with PSP. She had no documented dysautonomia or cerebellar signs, and
      imaging studies were not diagnostic of MSA. Pathological examination showed tau
      immunoreactive neuronal and glial lesions consistent with PSP as well as alpha
      synuclein immunoreactive glial cytoplasmic inclusions diagnostic of MSA. Double
      immunolabeling studies showed no co-localization of alpha-synuclein and tau in
      most neuronal and glial lesions. Based upon the findings in this case, the
      neuropathologic changes of PSP and MSA are distinct and independent processes,
      but they can occasionally coexist.

PMID- 16456666
TI  - Beta-protein/A4 deposits are not associated with hyperphosphorylated tau in
      somatostatin neurons in the hypothalamus of Alzheimer's disease patients.
AB  - With respect to the pathogenesis of Alzheimer's disease (AD), it has been
      hypothesized that amorphous plaques containing beta-protein/A4 (Abeta) would
      locally induce cytoskeletal changes, and that neurons affected by neurofibrillary
      tangles (NFTs) lose their neuropeptide concentration and eventually die. To test
      this presumed cascade of events, the hypothalami of 14 non-demented subjects
      (Braak 0-III) and 28 AD patients (Braak IV-VI) aged 40-98 years were selected.
      The subject of our study was the nucleus tuberalis lateralis (NTL), which harbors
      a subpopulation of somatostatinergic neurons with extensive intrinsic
      interconnectivity. We used Gallyas silver staining, Congo staining, single- and
      double-staining with monoclonal antibody AT8 and polyclonal antibody anti-Abeta,
      and double-immunolabeling with AT8 and anti-somatostatin(1-12) with the following
      results: (1) Significant amounts of silver-staining NFTs were present in only
      three AD patients. (2) High densities of AT8-stained cytoskeletal changes were
      mainly found in aged, demented patients. (3) In contrast, large amounts of Abeta
      deposits were mainly observed in young and middle-aged (40-59 years) AD patients,
      and were very low or absent mainly in the older non-demented subjects and in AD
      patients. (4) Reduced anti-somatostatin staining was observed in the NTL of most
      AD patients, but anti-somatostatin/AT8 double-stained neurons were found
      virtually exclusively in aged AD patients. Thus, the occurrence of Abeta deposits
      and hyperphosphorylated tau formation in somatostatin cells are basically
      independent events, while decreased somatostatin staining only partly goes
      together with cytoskeletal changes in somatostatin cells in the NTL of AD
      patients. These observations cannot be explained by the amyloid cascade
      hypothesis.

PMID- 16456667
TI  - GAT1 and GAT3 expression are differently localized in the human epileptogenic
      hippocampus.
AB  - The gamma amino butyric acid (GABA) transporters GAT-1 and GAT-3 were localized
      by immunohistochemistry in hippocampi removed for the control of medically
      intractable temporal lobe epilepsy (TLE). The study aimed to determine the
      relationship of GABA transporter expression to known patterns of hippocampal
      hyperexcitability and extracellular GABA levels. GAT-1 was localized in axon
      terminals and small neuronal cell bodies, and in non-sclerotic hippocampi was
      strongly expressed throughout all regions of the hippocampal formation. In the
      epileptogenic hippocampus exhibiting Ammon's horn sclerosis, immunoreactivity was
      reduced in the sclerotic regions CA3 and CA1, and around the cell bodies of
      dentate granule cells, but was increased along granule cell dendrites. GAT-3 was
      weakly expressed, if at all, in non-sclerotic hippocampi, but more prominently
      expressed in sclerotic hippocampi. GAT-3 expression was confined to cells
      resembling protoplasmic astrocytes, which were located in regions of relative
      neuronal sparing such as the dentate gyrus and hilus of the sclerotic
      hippocampus. The reduction in GAT-1 around granule cells in the sclerotic
      hippocampus could explain the prolonged GABA responses in this region. The loss
      of GAT-1 (a marker of GABAergic terminals) would also suggest a reduced GABAergic
      input to the granule cells, thus facilitating hyperexcitability. The increased
      GAT-3 expression in astrocytes in regions of relative neuronal sparing in the
      sclerotic hippocampus may be related to the overall low levels of extracellular
      GABA observed in the sclerotic hippocampus and their increased excitability.

PMID- 16456668
TI  - Upregulation of type I interleukin-1 receptor after traumatic spinal cord injury
      in adult rats.
AB  - Post-traumatic inflammation response has been implicated in secondary injury
      mechanisms after spinal cord injury (SCI). Interleukin-1 (IL-1) is a key
      inflammatory mediator that is increasingly expressed after SCI. The action of IL
      1 is mediated through its functional receptor, type I interleukin-1 receptor (IL
      1RI). However, whether this receptor is expressed after SCI remains to be
      elucidated. In the present study, the temporospatial expression of IL-1RI was
      detected in rats that received a moderate contusive SCI (a 10 g rod dropped at a
      height of 12.5 mm) at the ninth to tenth thoracic vertebral level using a widely
      used New York University impact device. Our study demonstrated that IL-1RI was
      slightly increased at 4 h post-injury compared to the normal or sham-operated
      controls, reached the peak at 8 h at mRNA level (4.44-fold, P<0.01) and 1 d at
      protein level (2.62-fold, P<0.01). IL-1RI remained at its elevated levels for a
      relatively long duration (4 h-7 days). Spatially, IL-1RI was observed throughout
      the entire length of a 10 mm-long cord segment containing the injury epicenter.
      Colocalization of IL-1RI was found in neurons, oligodendrocytes, astrocytes, and
      activated microglia. Our results suggest that the elevated expression of IL-1RI
      after SCI may contribute to posttraumatic inflammation responses of IL-1.

PMID- 16456669
TI  - Neocortical neuronal arrangement in Miller Dieker syndrome.
AB  - Miller Dieker syndrome (MDS, type I lissencephaly) is a neuronal migration
      disorder, which is caused by deletions along the short arm of chromosome 17
      (17p13.3). Recent studies would suggest that the cortical lamination in MDS is
      inverted, based on morphological criteria. The present neuropathological study
      examines the cerebral cortex from a 33-week old fetus with MDS using both
      neuronal and laminar-specific markers. These expression studies demonstrate a
      relatively preserved cortex and cortical lamination, overlying a layer of
      immature neurons in MDS brain. The findings are consistent with both a migratory
      and proliferative defect, giving rise to lissencephaly. Moreover,
      characterization of such rare human malformations of cortical development by
      immunohistochemical techniques will provide a greater understanding of the
      underlying mechanisms.

PMID- 16456670
TI  - Condensed-history Monte Carlo simulation of the dosimetric distribution of
      electron microbeam.
AB  - To evaluate the dose distributions of an electron microbeam and to help
      optimization of its design, the condensed-history (CH) Monte Carlo simulation
      algorithm implemented in the Geant4 toolkit was selected as an alternative to the
      conventionally used analog algorithm. Compared to the analog algorithm, the CH
      algorithm is cheaper and less limited by the lack of cross-sections. And, with a
      properly chosen production cut for secondaries, its accuracy for the problems of
      microdosimetry is satisfactory. In this work, calculations of the single-event
      (imparted energy epsilon) size distribution f (1)(epsilon) is described, for
      compartments in the Orlando electron micro beam. The results agree well with
      those obtained by use of the analog algorithm and reported in the literature. It
      is shown that substituting tissue with water in HeLa cells, and replacing Mylar
      with water of the same mass stopping power in the substrate, makes little
      difference. Additionally, the neighbor-to-target ratio of average event size R
      (NT) has been calculated as a function of the incident energy of the electrons.
      Comparison with analog results reported in the literature suggests that the
      average event size in neighbors, and hence the neighbor-to-target ratio, is
      sensitive to the selection of the energy threshold. Finally, the effect of finite
      beam radius on the event size distribution and the neighbor-to-target ratio has
      also been studied. All results presented suggest the condensed-history technique
      to provide an efficient and valuable alternative tool in the design of electron
      microbeams.

PMID- 16456671
TI  - Comparison of EPR occupational lifetime external dose assessments for Mayak
      nuclear workers and film badge dose data.
AB  - The Mayak worker cohort is one of the major sources of information on health
      risks due to protracted exposures to plutonium and external ionizing radiation.
      Electron paramagnetic resonance (EPR) measurements in tooth enamel in combination
      with personal dose monitoring can help to improve external dose assessment for
      this cohort. Here, the occupational lifetime external exposure was evaluated
      individually for 44 nuclear workers of three plants of the Mayak Production
      Association by EPR measurements of absorbed doses in collected tooth enamel
      samples. Analysis included consideration of individual background doses in enamel
      and dose conversion coefficients specific for photon spectra at selected work
      areas. As a control, background doses were assessed for various age groups by EPR
      measurements on teeth from non-occupationally exposed Ozyorsk residents.
      Differences in occupational lifetime doses estimated from the film badges and
      from enamel for the Mayak workers were found to depend on the type of film badge
      and the selected plant. For those who worked at the radiochemical processing
      plant and who were monitored with IFK film badges, the dose was on average 570
      mGy larger than estimated from the EPR measurements. However, the average
      difference was found to be only -4 and 6 mGy for those who were monitored with
      IFKU film badges and worked at the reactor and the isotope production plant
      respectively. The discrepancies observed in the dose estimates are attributed to
      a bias in film badge evaluation.

PMID- 16456672
TI  - Neuromuscular factors determining 5 km running performance and running economy in
      well-trained athletes.
AB  - This study investigated the effects of the neuromuscular and force-velocity
      characteristics in distance running performance and running economy. Eighteen
      well-trained male distance runners performed five different tests: 20 m maximal
      sprint, running economy at the velocity of 4.28 m s(-1), 5 km time trial, maximal
      anaerobic running test (MART), and a treadmill test to determine VO2max. The AEMG
      ratio was calculated by the sum average EMG (AEMG) of the five lower extremity
      muscles during the 5 km divided by the sum AEMG of the same muscles during the
      maximal 20 m sprinting. The runners' capacity to produce power above VO2max (MART
      VO2gain) was calculated by subtracting VO2max from the oxygen demand of the
      maximal velocity in the MART (V MART). Velocity of 5 km (V 5K) correlated with V
      MART (r=0.77, p<0.001) and VO2max (r=0.49, p<0.05). Multiple linear regression
      analysis showed that MART VO2gain and VO2max explained 73% of the variation in V
      5K. A significant relationship also existed between running economy and MART
      VO2gain (r=0.73, p<0.01). A significant correlation existed between V 5K and AEMG
      ratio during the ground contact phase at the 3 km (r=0.60, p<0.05) suggesting
      that neural input may affect distance running performance. The results of the
      present study support the idea that distance running performance and running
      economy are related to neuromuscular capacity to produce force and that the V
      MART can be used as a determinant of distance-running performance.

PMID- 16456673
TI  - Training-induced changes in membrane transport proteins of human skeletal muscle.
AB  - Training improves human physical performance by inducing structural and
      cardiovascular changes, metabolic changes, and changes in the density of membrane
      transport proteins. This review focuses on the training-induced changes in
      proteins involved in sarcolemmal membrane transport. It is concluded that the
      same type of training affects many transport proteins, suggesting that all
      transport proteins increase with training, and that both sprint and endurance
      training in humans increase the density of most membrane transport proteins.
      There seems to be an upper limit for these changes: intense training for 6-8
      weeks substantially increases the density of membrane proteins, whereas years of
      training (as performed by athletes) have no further effect. Studies suggest that
      training-induced changes at the protein level are important functionally. The
      underlying factors responsible for these changes in transport proteins might
      include changes in substrate concentration, but the existence of "exercise
      factors" mediating these responses is more likely. Exercise factors might include
      Ca(2+), mitogen-activated protein kinases, adenosine monophosphate kinases, other
      kinases, or interleukin-6. Although the magnitudes of training-induced changes
      have been investigated at the protein level, the underlying signal mechanisms
      have not been fully described.

PMID- 16456674
TI  - Independent and combined effects of liquid carbohydrate/essential amino acid
      ingestion on hormonal and muscular adaptations following resistance training in
      untrained men.
AB  - This investigation examined chronic alteration of the acute hormonal response
      associated with liquid carbohydrate (CHO) and/or essential amino acid (EAA)
      ingestion on hormonal and muscular adaptations following resistance training.
      Thirty-two untrained young men performed 12 weeks of resistance training twice a
      week, consuming ~675 ml of either, a 6% CHO solution, 6 g EAA mixture, combined
      CHO + EAA supplement or placebo (PLA). Blood samples were obtained pre- and post
      exercise (week 0, 4, 8, and 12), for determination of glucose, insulin, and
      cortisol. 3-Methylhistidine excretion and muscle fibre cross-sectional area
      (fCSA) were determined pre- and post-training. Post-exercise cortisol increased
      (P<0.05) during each training phase for PLA. No change was displayed by EAA; CHO
      and CHO + EAA demonstrated post-exercise decreases (P<0.05). All groups displayed
      reduced pre-exercise cortisol at week 12 compared to week 0 (P<0.05). Post
      exercise insulin concentrations showed no change for PLA; increases were observed
      for the treatment groups (P<0.05), which remained greater for CHO and CHO + EAA
      (P<0.001) than PLA. EAA and CHO ingestion attenuated 3-methylhistidine excretion
      48 h following the exercise bout. CHO + EAA resulted in a 26% decrease (P<0.01),
      while PLA displayed a 52% increase (P<0.01). fCSA increased across groups for
      type I, IIa, and IIb fibres (P<0.05), with CHO + EAA displaying the greatest
      gains in fCSA relative to PLA (P<0.05). These data indicate that CHO + EAA
      ingestion enhances muscle anabolism following resistance training to a greater
      extent than either CHO or EAA consumed independently. The synergistic effect of
      CHO + EAA ingestion maximises the anabolic response presumably by attenuating the
      post-exercise rise in protein degradation.

PMID- 16456676
TI  - Riboflavin-like inmunoreactive fibers in the monkey brain.
AB  - Using an antiserum directed against the vitamin riboflavin, we studied the
      distribution of riboflavin-like immunoreactive structures in the monkey brain. In
      the mesencephalon, at the level of the mesencephalic-diencephalic junction,
      single riboflavin-like immunoreactive fibers were observed in its dorsal part,
      whereas a low density of immunoreactive fibers was found below the surface of the
      section and close to substantia nigra, and a high density was observed above the
      substantia nigra and close to the medial geniculate nucleus. In the thalamus,
      single riboflavin-like immunoreactive fibers were found in the ventral regions of
      the lateral posterior and the medial geniculate nuclei; a low density in the
      region located above the medial and lateral geniculate nuclei and a high density
      in the ventral part of the pulvinar nucleus and in the region extending from this
      latter to the caudate nucleus. Immunoreactive fibers were not observed in the
      medulla oblongata, pons, cerebellum, hypothalamus, basal ganglia and cerebral
      cortex. Moreover, no riboflavin-like immunoreactive cell bodies were observed in
      the monkey brain. The distribution of riboflavin-like immunoreactive fibers in
      the monkey suggests that this vitamin could be involved in several physiological
      mechanisms.

PMID- 16456675
TI  - TIS21 (/BTG2/PC3) as a link between ageing and cancer: cell cycle regulator and
      endogenous cell death molecule.
AB  - TIS21(/BTG2/PC3), orthologs of mouse, human and rat, respectively, is initially
      identified as one of the early growth response genes and induced by various
      stimulations. TIS21 belongs to antiproliferative (APRO) gene family containing
      the BTG-Box A (Y(50)-N(71)) and BTG-Box B (L(97)-E(115)), which are highly
      conserved among various species. On the other hand, it has lately been found that
      the expression of TIS21 is constitutive and high in thymus, lung alveolar
      epithelium, proximal tubule of kidney and basal cell layer of prostate acini.
      Potential roles of TIS21 have been suggested as transcriptional co-regulator,
      differentiation and antiapoptotic factor in neurogenesis, key mediator of the
      stage-specific expansion of thymocyte and negative regulator of hematopoietic
      progenitor expansion, and tumor suppressor gene in both mouse and human. In
      addition, as pan-cell cycle regulator TIS21 induces G1/S arrest by pRB
      dependently and pRB independently and G2/M arrest and cell death in the p53 null
      tumor cells, and regulates the development of vertebrate patterning in mouse,
      paraxial mesoderm development in zebrafish, and notochord development in Xenopus.
      It has been known that the expression of TIS21 depends on the induction of wt p53
      when cells are damaged, however, it can also be upregulated p53 independently by
      the activation of PKC-delta pathway in tumor cells. The characteristic roles of
      TIS21 are discussed in the present review: (1) TIS21 inhibits early phase of
      carcinogenesis in its high expressers such as kidney, prostate, breast and
      thymus: Loss of constitutive and high expression of TIS21 was observed in the
      precancerous lesions as well as tumor tissues. As an endogenous cell death
      molecule, TIS21 may be involved in translocation of Pin-1 to cytoplasm. Pin-1
      subsequently interacts with Serine(147) residue in TIS21 protein, resulting in
      mitochondrial depolarization. (2) TIS21 regulates transition of cell cycle at
      G1/S and G2/M phases in cancer cells with inactive pRB and/or p53, as well as in
      normal cells by regulating pRB/p16(INK4a) pathway. The latter has already been
      well elucidated; TIS21 inhibits the expression of cyclin D1, thus resulting in
      the arrest of cells at G1/S phase by pRB and p53 dependent manner. On the other
      hand, TIS21 inhibits degradations of cyclin A and cyclin B1 at G2/M phase, and
      directly binds to Cdc2, resulting in the failure of mitotic exit and then
      increasing the tumor cell death, when stimulated by high concentration of EGF.
      Therefore, TIS21 can be suggested as a pan-cell cycle modulator. (3) TIS21
      regulates embryo development by activating BMP signal through interaction with
      Smad 1 and Smad 8, thereby regulating vertebral patterning in mice. It is also
      involved in notochord development in Xenopus and paraxial mesoderm development in
      zebrafish. Based on the previous report that the expression of TIS21 is involved
      in the induction of senescence after chemotherapy of cancer cells, which can be a
      mechanism to resist carcinogenesis, TIS21(/BTG2/PC3), the endogenous cell death
      molecule and pan-cell cycle regulator, might be a link between cellular
      senescence and carcinogenesis.

PMID- 16456677
TI  - Expression and regulation of the LIM homeodomain gene L3/Lhx8 suggests a role in
      upper lip development of the chick embryo.
AB  - LIM-homeodomain (Lhx) genes constitute a gene family that plays critical roles in
      the control of pattern formation and cell type specification. We have identified
      a chicken L3/Lhx8 gene, which was widely expressed in the craniofacial region.
      Whole-mount in situ hybridization showed that L3/Lhx8 mRNA was expressed from
      stage 15--31 HH in overlapping domains of the maxillary process. Frozen sections
      revealed these signals in the mesenchyme underneath the epithelium. To determine
      whether the expression of L3/Lhx8 in the maxillary primordia required signals
      from the overlying oral epithelium, maxillary processes of stage 23 HH chick
      embryos were transplanted into the limb bud, in which the mesenchyme was grown in
      the presence or absence of oral epithelium. The maxillary mesenchyme with
      epithelium showed significant levels of L3/Lhx8 gene expression. In contrast, no
      expression of L3/Lhx8 was detected in the epithelium-free mesenchyme. To further
      explore signaling molecule(s) responsible for Lhx induction, a bead, soaked in
      either Fgf-8b or TGF-beta3, was implanted into an epithelium-free mesenchymal
      graft. Both TGF-beta3 and Fgf-8b beads induced expressions of L3/Lhx8 in
      epithelium-free mesenchymal grafts. Our data suggest that the L3/Lhx8 gene
      contributes to epithelial mesenchymal interaction in facial morphogenesis and
      that Fgf-8b and TGF-beta3 were, at least in part, responsible for the Lhx
      expression in the maxillary process.

PMID- 16456678
TI  - Microvascularization of thalamus and metathalamus in common tree shrew (Tupaia
      glis).
AB  - The microangioarchitecture of the thalamus and metathalamus in common tree shrew
      (Tupaia glis) was studied using vascular corrosion cast/stereomicroscope and SEM
      technique. The arterial supply of the thalamus and metathalamus was found to
      originate from perforating branches of the posterior communicating artery, the
      posterior cerebral artery, the middle cerebral artery, and the anterior choroidal
      artery. These perforating arteries gave rise to numerous bipinnate arterioles
      which in turn, with decreasing vessel diameters, branched into a non-fenestrated
      capillary bed. Venous blood from the superficial parts of the thalamus and
      metathalamus was collected into the thalamocollicular vein, whereas venous blood
      from internal aspects of the thalamus was conveyed to the internal cerebral vein.
      Some venous blood from the most rostral part of the thalamus flowed into
      tributaries of the middle cerebral vein before draining into the cavernous sinus.
      Further, the thalamic and metathalamic vascular arrangement was found to be of
      centripetal type. In addition, thalamic arterial anastomosis was rarely observed.
      Thus, obstruction of thalamic blood supply could easily lead to thalamic
      infraction.

PMID- 16456679
TI  - Phosphorylation of c-Jun N-terminal kinase (JNK) in sensory neurones of diabetic
      rats, with possible effects on nerve conduction and neuropathic pain: prevention
      with an aldose reductase inhibitor.
AB  - AIMS/HYPOTHESIS: This study was designed to determine whether diabetes in rats is
      associated with phosphorylation of c-Jun N-terminal kinase (JNK) and one of its
      transcription factors, c-Jun, in sensory neurones innervating the lower limb. We
      also sought to determine which neuronal phenotypes are affected and to examine
      the effect of aldose reductase inhibition on JNK and c-Jun phosphorylation.
      METHODS: Diabetes was induced in rats using streptozotocin. Phosphorylation of
      JNK and c-Jun in lumbar dorsal root ganglia was determined by binding of phospho
      specific antibodies using western blots and immunocytochemistry. Neuronal
      phenotypes were characterised by binding of N52 (an antibody that recognises the
      heavy neurofilament protein; for large-diameter mechanoceptors) and of calcitonin
      gene-related peptide and the plant glycoprotein lectin IB4 (for nociceptors). The
      efficacy of the aldose reductase inhibitor fidarestat was determined by measuring
      polyol pathway metabolites in sciatic nerve, and functionally by measuring the
      conduction velocity of motor and sensory nerves. RESULTS: In control rats,
      activated JNK and c-Jun were primarily associated with mechanoceptors; in
      diabetes this was increased, but a greater increase was seen in nociceptors.
      Phosphorylation was prevented in all cells by fidarestat, which normalised polyol
      pathway metabolites as well as motor nerve and sensory nerve conduction velocity.
      CONCLUSIONS/INTERPRETATION: Fidarestat-sensitive phosphorylation of JNK and c-Jun
      occurs in fast-conduction mechanoceptors-the same class of neurones that
      registers the changes in sensory nerve conduction velocity-and in nociceptors.
      This supports the notion that mitogen-activated protein kinase phosphorylation,
      via the polyol pathway, may convert the direct effects of raised glucose into
      impaired nerve conduction and neuropathic pain. For proof of this we await the
      availability of specific JNK antagonists formulated for in vivo use.

PMID- 16456680
TI  - Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET
      study.
AB  - AIMS/HYPOTHESIS: In type 2 diabetic patients we compared 9 months of combination
      therapy with insulin glargine and metformin with 9 months of NPH insulin combined
      with metformin. The primary focus was changes in HbA(1c); secondary focus was
      diurnal glucose profiles and symptomatic hypoglycaemia. METHODS: In this
      investigator-initiated open, parallel-group clinical trial involving seven
      centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control
      (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus
      metformin) were randomised to receive bedtime insulin glargine with metformin
      (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were
      taught how to self-adjust their insulin dose and use a modem to send the results
      of home glucose monitoring to treatment centres. The goal was to achieve a
      fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups. RESULTS: During
      the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and
      insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(
      1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean
      HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not
      confirmed symptomatic, hypoglycaemia was significantly lower during the first 12
      weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET
      group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different
      thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/
      0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36
      week study. With regard to baseline characteristics such as initial glycaemia or
      C-peptide, there was no difference between patients who achieved good glycaemic
      control (HbA(1c) <7.0%) and those who did not. Differences were seen in the
      following: between study centres, weight gain during the run-in period and
      insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l
      for patients reaching vs those not reaching target, p<0.01).
      CONCLUSIONS/INTERPRETATION: Good glycaemic control can be achieved with both
      G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the
      first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.

PMID- 16456682
TI  - Ethnic differences in beta cell adaptation to insulin resistance in obese
      children and adolescents.
AB  - AIMS/HYPOTHESIS: The prevalence of altered glucose metabolism in obese children
      and adolescents is growing at a significant rate, especially in ethnic
      minorities. It is not clear whether young people of different ethnic backgrounds
      differ in their adaptive mechanisms to obesity-related insulin resistance. The
      aim of this study was to evaluate the early insulin response and insulin
      clearance in response to an oral glucose load in obese children and adolescents.
      METHODS: Seven hundred and nine obese children and adolescents underwent an OGTT.
      Indices of the early insulin response and insulin clearance were compared in
      participants of White European, African American and Hispanic origin. RESULTS:
      Participants of the three ethnic groups demonstrated similar mechanisms of
      adaptation to increasing insulin resistance, but with different magnitudes.
      African American subjects had a greater early insulin response and decreased
      insulin clearance than their White European and Hispanic counterparts. This
      happened regardless of whether the cohort was divided by glucose tolerance level
      or by level of insulin sensitivity. IGT across ethnic groups was characterised by
      a marked decline in the acute insulin response in the context of severe insulin
      resistance and very low insulin clearance. CONCLUSIONS/INTERPRETATION: In obese
      children and adolescents, mechanisms of adaptation to obesity related to insulin
      resistance are similar across ethnic groups. The greater early insulin response
      needed to maintain glucose tolerance in young people of ethnic minorities may
      partially explain their greater tendency to develop type 2 diabetes.

PMID- 16456683
TI  - Rate code and temporal code for frequency of whisker stimulation in rat primary
      and secondary somatic sensory cortex.
AB  - We recorded responses to frequencies of whisker stimulation from 479 neurons in
      primary (S1) and secondary (S2) somatic sensory cortex of 26 urethane
      anesthetized rats. Five whiskers on the right side of the snout were deflected
      with air puffs at seven frequencies between 1 and 18/s. In left S1 (barrels and
      septa) and S2, subsets of neurons (5%) responded to whisker stimulation across
      the entire range of frequencies with > or = 1 electrical discharges/ten stimuli
      (full responders). In contrast, 60% of the recorded cells responded above
      threshold only at stimulus frequencies below 6/s and 35% remained subthreshold at
      all frequencies tested. Thus, the full responders are unique in that they were
      always responsive and appeared particularly suited to facilitate a dynamic,
      broadband processing of stimulus frequency. Full responders were most responsive
      at 1 stimulus/s, and showed greatest synchrony with whisker motion at 18
      stimuli/s. The barrel cells responded with the greatest temporal accuracy between
      3 and 15 stimuli/s. The septum cells responded less accurately, but maintained
      their accuracy at all frequencies. Only septum cells continued to increase their
      discharge rate with increasing stimulus frequency. The S2 cells discharged with
      lowest temporal accuracy modulated only by stimulus frequencies < or = 6/s and
      exhibited the steepest decrease in discharge/stimulus with increasing stimulus
      frequency. Our observations suggest that full responders in the septa are well
      suited to encode high frequencies of whisker stimulation in timing and rate of
      discharge. The barrel cells, in contrast, showed the strongest temporal coding at
      stimulus frequencies in the middle range, and S2 cells were most sensitive to
      differences in low frequencies. The ubiquitous decline in discharge/stimulus in
      S1 and S2 may explain the decrease in blood flow observed at increasing stimulus
      frequency with functional imaging.

PMID- 16456685
TI  - Why islands are easier to invade: human influences on bullfrog invasion in the
      Zhoushan archipelago and neighboring mainland China.
AB  - Islands are often considered easier to invade than mainland locations because of
      lower biotic resistance, but this hypothesis is difficult to test. We compared
      invasion success (the probability of establishing a wild reproducing population)
      for bullfrogs (Rana catesbeiana) introduced to enclosures on 26 farms on islands
      in the Zhoushan archipelago and 15 farms in neighboring mainland China. Bullfrogs
      were more likely to invade farms located on islands with lower native frog
      species richness than mainland farms, consistent with the biotic resistance
      hypothesis. However, human frog hunting pressure also differed between islands
      and the mainland and, along with the number of bullfrogs raised in enclosures,
      was a stronger predictor of invasion success than native frog richness in
      multiple regression. Variation in hunting pressure was also able to account for
      the difference in invasion success between islands and mainlands: islands had
      lower hunting pressure and thus higher invasion probability. We conclude that the
      ease with which bullfrogs have invaded islands of the Zhoushan archipelago
      relative to the mainland has little to do with biotic resistance but results from
      variation in factors under human control.

PMID- 16456684
TI  - Nutrient and water addition effects on day- and night-time conductance and
      transpiration in a C3 desert annual.
AB  - Recent research has shown that many C3 plant species have significant stomatal
      opening and transpire water at night even in desert habitats. Day-time stomatal
      regulation is expected to maximize carbon gain and prevent runaway cavitation,
      but little is known about the effect of soil resource availability on night-time
      stomatal conductance (g) and transpiration (E). Water (low and high) and
      nutrients (low and high) were applied factorially during the growing season to
      naturally occurring seedlings of the annual Helianthus anomalus. Plant height and
      biomass were greatest in the treatment where both water and nutrients were added,
      confirming resource limitations in this habitat. Plants from all treatments
      showed significant night-time g (approximately 0.07 mol m(-2) s(-1)) and E
      (approximately 1.5 mol m(-2) s(-1)). In July, water and nutrient additions had
      few effects on day- or night-time gas exchange. In August, however, plants in the
      nutrient addition treatments had lower day-time photosynthesis, g and E,
      paralleled by lower night-time g and E. Lower predawn water potentials and higher
      integrated photosynthetic water-use efficiency suggests that the nutrient
      addition indirectly induced a mild water stress. Thus, soil resources can affect
      night-time g and E in a manner parallel to day-time, although additional factors
      may also be involved.

PMID- 16456686
TI  - Rapid turnover of tissue nitrogen of primary consumers in tropical freshwaters.
AB  - Stable isotopes are widely used as time-integrating tracers of trophic
      interactions, but turnover rates of isotopes in animal tissues remain poorly
      understood. Here, we report nitrogen (N) isotope turnover rates in tissues of
      four primary consumer species: Ancistrus triradiatus armored catfish (muscle,
      fins, and whole blood), Tarebia granifera snails (muscle), and Rana palmipes
      tadpoles (muscle) from a Venezuelan river, and Lavigeria grandis snails (muscle)
      from Lake Tanganyika, East Africa. Turnover was estimated from the dilution of a
      15N label introduced into consumer tissues by feeding on 15N-enriched periphyton.
      Muscle turnover rates were rapid (0.5-3.8% per day), and were attributable to
      metabolic replacement of N as well as growth in catfish and snails. N turnover in
      catfish muscle decreased with size, and fin tissue turned over more rapidly than
      whole blood or muscle, though the difference was not significant. Our results
      indicate that stable isotope signatures of these tropical species could change
      markedly within weeks following a shift in diet. However, generalization across
      taxa or latitudes is complicated by the strong size-dependence of isotope
      turnover rates. The enrichment-dilution approach outlined here may facilitate
      measurement of isotopic turnover in a wide variety of consumers under field
      conditions.

PMID- 16456687
TI  - Sexual dimorphism, activity budget and synchrony in groups of sheep.
AB  - The activity budget hypothesis has been proposed to explain the social
      segregation commonly observed in ungulate populations. This hypothesis suggests
      that differences in body size--i.e. between dimorphic males and females--may
      account for differences in activity budget. In particular, if females spend more
      time grazing and less time resting than males, activity synchrony would be
      reduced. Increased costs of maintaining synchrony despite differences in activity
      budget would facilitate group fragmentation and instability of mixed-sex groups.
      In this paper two prerequisites of the activity budget hypothesis were tested:
      (1) that males should spend less time feeding and more time resting than females
      in single-sex groups and (2) that lower activity synchrony should be observed in
      mixed-sex compared to single-sex groups. The activity budget and synchrony in
      mixed and single-sex groups of merino sheep (Ovis aries) of different sizes (2,
      4, 6, 8 individuals) were measured in three contiguous 491-m2 arenas located in a
      natural pasture. Three same-size groups, one of each category, were observed
      simultaneously. We found no sexual differences in the time spent inactive and
      active (i.e. grazing, standing, moving, interacting). Males spent significantly
      more time grazing and less time standing than females. These differences
      disappeared when yearling males were omitted from the group. Males and females
      had similar bite and step rates. Sheep of both sexes spent less time resting and
      more time grazing and moving and had lower bite rates when in mixed-sex groups
      than when in single-sex groups. The synchrony among visually isolated groups was
      near zero, indicating that they changed activities independently. On the
      contrary, within-group synchrony was high; however it was higher in single-sex
      groups, in particular for males, than in mixed-sex groups. Our results suggest
      that differences in activity budget and synchrony alone are insufficient to
      explain social segregation.

PMID- 16456689
TI  - Isolated Langerhans cell histiocytosis of the infundibulum presenting with
      fulminant diabetes insipidus.
AB  - INTRODUCTION: Langerhans cell histiocytosis (histiocytosis X) is a rare disorder
      that can manifest with solitary bony lesions or disseminated disease in various
      tissues. A common manifestation of the disease is diabetes insipidus even in the
      absence of neural involvement. Disseminated disease often involves the central
      nervous system, but only six isolated lesions in the infundibulum have been
      reported. CASE REPORT: An 18-year-old male had failed to develop secondary sexual
      characteristics. He also had diabetes insipidus for more than 1 year. Magnetic
      resonance imaging (MRI) of the brain showed a 1-cm homogeneously enhancing mass
      in the region of the infundibulum. No other lesions were found in other organ
      systems. The patient underwent an orbitozygomatic osteotomy and pterional
      craniotomy. The lesion, which was adherent to the infundibulum, was partially
      resected. Microscopic analysis showed multiple lymphocytes and eosinophils with
      Langerhans cells that stained positive for S-100. Langerhans cell histiocytosis
      was diagnosed, and the patient was discharged on postoperative day 6 with no
      neurological deficits. His diabetes insipidus persisted, and he underwent
      intensity-modulated radiation therapy to the sellar region. CONCLUSIONS: Isolated
      Langerhans cell histiocytosis of the infundibulum is rare. The usual presentation
      is hypothalamic-pituitary axis dysfunction and diabetes insipidus. Patients with
      diabetes insipidus of unknown origin should undergo MRI of the sellar region to
      rule out infundibular abnormalities.

PMID- 16456688
TI  - [Bisphosphonate-associated osteonecrosis of the jaw].
AB  - BACKGROUND: Bisphosphonates (BP) are widely used in patients with osteoporosis or
      malignant tumors with bony metastases such as breast cancer and plasmocytoma
      because of their potency to affect osteoclasts and bone resorption. Osteonecrosis
      of the jaw (ONJ) has been described as a potential side effect since 2003. After
      a review of the literature we present results of a questionnaire, which was sent
      to departments of oral and maxillofacial surgery (OMFS) in German-speaking
      countries. MATERIAL AND METHODS: We present 349 patients from the literature, 54
      patients from the departments of OMFS and 19 cases from our own department. These
      patients ware analyzed depending on their disease, their medication, localization
      of the affected area, histological signs and therapeutic outcome. RESULTS: Of 73
      patients, 68 (93%) were treated with pamidronate or zoledronate; 69 (94%)
      patients suffered from malignant diseases, 3 (5%) had osteoporosis, and 1 (1%)
      had Paget's disease. In 57 (78%) patients the ONJ affected the mandible, in 12
      (16%) the maxilla and in 4 (5%) both jaws. A previous tooth extraction was
      reported in 38 (52%) patients, and in 35 (48%) ONJ occurred spontaneously.
      Histological findings were similar to osteomyelitis with a high number of
      actinomyces colonies. Nine (12%) patients received non-surgical treatment only,
      52 (71%) patients underwent minor surgical procedures (e. g. decortication) and
      19 (26%) patients underwent marginal or segmental resection of the jaw.
      Considering all treatment modalities, healing was achieved in 55; the most
      effective was marginal and segmental resection (88%). DISCUSSION: Though millions
      of patients receive BP treatment only a few suffer from ONJ. The incidence in
      cancer patients with pamidronate and zoledronate therapy is 4%-10%. Because of
      the similarity to "phossy jaw", seen in patients dealing with white phosphorus in
      the nineteenth century, some authors call the new entity "bis-phossy jaw". As the
      pathogenesis of ONJ is not clear we recommend that the descriptive term
      bisphosphonate-associated osteonecrosis should be used. Bone resection and safe
      soft tissue closure is the treatment of choice. We recommend systematic dental
      care for patients receiving BP medication. Information exchange between
      oncologists, oral and maxillofacial surgeons and dentists is important.

PMID- 16456690
TI  - Malignant meningioma as a second malignancy after therapy for acute lymphatic
      leukemia without cranial radiation.
AB  - RATIONALE: Meningiomas in the pediatric age group are very rare tumors,
      comprising about 1-4.2% of all primary pediatric intracranial tumors. CASE
      REPORT: We present a 17-year-old patient who suffered from an intraventricular
      malignant meningioma. At the age of 2 years, acute lymphatic leukemia (common ALL
      [cALL]) was diagnosed and successfully treated with chemotherapy. There was no
      cranial radiation therapy. In December 2001, 13 years after diagnosis of cALL, he
      complained of headache, vomiting, and walking difficulties. Magnetic resonance
      imaging showed an enhancing mass with cystic components in the trigone of the
      right lateral ventricle. The tumor was removed completely. Histological diagnosis
      revealed a malignant papillary meningioma. After removal of a recurrent
      meningioma 16 months later, he received local radiotherapy. CONCLUSION:
      Pathogenetic mechanisms, treatment options, and prognosis of meningiomas and
      secondary malignancies of this age group are discussed.

PMID- 16456692
TI  - The role of computed tomography in endoscopic sinus surgery: a review of 10
      years' practice.
AB  - CT scans from 100 patients undergoing endoscopic sinus surgery (ESS) were
      primarily re-examined in order to assess the quality of the radiological
      examinations and the information it could provide years later. The material
      comprised the cases of patients who had undergone ESS by one surgeon (AD) in the
      1990s. The indications for surgery were acute recurrent or chronic sinus
      infections, polyposis of the nasal and paranasal cavities, mucoceles and
      sinogenic headache. All examinations were described using a scheme modified
      according to Stoney et al., evaluating the opacity/mucosal thickening,
      drainage/pathways, the lateral nasal walls, septum and other bony walls. This
      study has been re-evaluated and an additional group of 20 patients consecutively
      operated on in 2002/2003 has been added. The initial radiological examinations
      often proved incomplete, with insufficient descriptions of either the
      drainage/pathways, the lateral nasal wall or the septum and bony walls, which all
      are structures of great value to evaluate preoperatively for the endoscopic
      surgeon. The operative findings correlated well with the CT if taken between 4-6
      weeks before the operation. The structural pathology correlated with preoperative
      endoscopic findings independently of the time lapse between the scans taken and
      the date of surgery. The development and the gradual implementation of the
      picture archiving and communication system (PACS) certainly represent huge
      advantages in radiological assessment. The need for CT scans to be available in
      the operating room calls for specific computer installations to make PACS readily
      available peroperatively and in an easily workable way for the surgeon.

PMID- 16456693
TI  - Interleukin 5, IL6, IL12, IFN-gamma, RANTES and Fractalkine in human nasal
      polyps, turbinate mucosa and serum.
AB  - Polyps are considered to develop as an end result of an inflammatory process.
      Cytokines and chemokines in the respiratory mucosa may be a key to polyp
      pathophysiology. The main objective was to identify IL-5, IL-6, IL-12, RANTES,
      IFN-gamma and Fractalkine in humans on the protein level in nasal polyps and
      mucosa from the inferior turbinate (IT). Furthermore, the cytokines and
      chemokines RANTES and Fractalkine were analyzed in plasma. Tissue homogenates and
      plasma from 13 patients were analyzed by the ELISA technique. All the patients
      had longstanding nasal/paranasal polyposis. Fractalkine was detected in polyps
      and IT in two different patients. IL-5 was expressed in polyps and IT. IL-6 was
      expressed in all patients with a higher level in polyps than IT. IL-12 was
      present in plasma, polyps and IT, though at an increased level in polyps. RANTES
      was present at a higher level in plasma than in polyps and IT. IFN-gamma was
      detectable in polyps and IT. Fractalkine is detected in nasal polyps, which is a
      new observation. The overall results indicate a mixed T(H)1/T(H)2 cytokine
      profile in nasal polyps. RANTES and IL-12 are strongly present in plasma,
      suggesting an ongoing inflammatory "drive". IL-6 and IL-12 are up-regulated in
      polyps versus the IT. Up-regulation of IL-6 may be explained by increased
      fibroblast activity dependant on an ongoing local inflammation possibly initiated
      by an infection. IL-5, RANTES and IFN-gamma are equally represented in polyps and
      IT, indicating equilibrium between the nasal polyps and surrounding tissue, and
      that an up-regulation of cytokines in the polyp indicates a potential for polyp
      growth.

PMID- 16456698
TI  - Abstracts from Acute Leukemias XI. Prognostic Factors and Treatment Strategies.
      February 18-22, 2006. Munich, Germany.

PMID- 16456694
TI  - Is prevention of stone recurrence financially worthwhile?
AB  - This review shows that the cost of relying solely on minimally-invasive
      urological procedures for removing stones when patients return with recurrent
      stones is considerable and is significantly greater that that incurred by
      screening already proven recurrent stone-formers to identify the risk factors
      that are causing their stones and then instituting prophylactic measures to
      prevent stone recurrence. In the UK, at 1998 prices (when the original survey was
      carried out) for every stone episode prevented, there is a potential saving of
      almost 2,000 pound to the local Health Authority concerned. In spite of this,
      many Health Authorities have taken the liberty to discontinue comprehensive stone
      screening within the past 20 years under the mistaken supposition that minimally
      invasive techniques for removing stones have "solved the stone problem". At UCLH
      in London where such a comprehensive scheme has been in place for the past 8
      years, savings of up to 250,000 pound per year can be made by identifying the
      particular lifestyle as well as the epidemiological, metabolic and nutritional
      risk factors involved in a given patient and then instituting appropriate
      measures to prevent further stones.

PMID- 16456701
TI  - 1H, 13C and 15N resonance assignments of the 2'-5' RNA ligase-like protein from
      Pyrococcus furiosus.

PMID- 16456702
TI  - NMR assignment of the E. coli-II cytolethal distending toxin CdtB subunit.

PMID- 16456703
TI  - NMR assignments of the free and bound-state protein components of an anti
      idiotypic affibody complex.

PMID- 16456704
TI  - NMR assignment of the dimeric S. aureus small multidrug-resistance pump in LPPG
      micelles.

PMID- 16456706
TI  - NMR assignment of rat Raf kinase inhibitor protein.

PMID- 16456705
TI  - 1H, 13C and 15N resonance assignments of the C-terminal domain of RP2.

PMID- 16456707
TI  - NMR assignment of the mTOR domain responsible for rapamycin binding.

PMID- 16456708
TI  - Molecular cloning, expression and characterization of the zebrafish bram1 gene, a
      BMP receptor-associated molecule.
AB  - We have identified a cDNA clone encoding BMP receptor-associated molecule 1
      (BRAM1) from the zebrafish expressed sequence tag (EST) database. The 2606 bp
      full-length bram1 cDNA was cloned, and further confirmed by nucleotide
      sequencing. The zebrafish sequence encodes a protein of 195 amino acids with an
      evolutionarily conserved MYND domain, which displays approximately approximately
      98% homology with human and mouse BRAM1, and approximately approximately 64%
      homology with C. elegans BRA-1 and BRA-2. The bram1 gene, composed of five exons
      and four introns, spans approximately approximately 14 kb on linkage group 14 of
      the zebrafish genome. RT-PCR and whole mount in situ hybridization analyses
      disclosed that zebrafish BRAM1 is a maternal factor. The protein interacts
      directly with zebrafish BMP Receptor type IA, as observed from GST-pull down and
      co-immunoprecipitation assays. Furthermore, cotransfection of zebrafish BRAM1
      with the corresponding BMP receptor resulted in down-regulation of BMP-mediated
      signaling. Our results collectively indicate that BRAM1 plays a biological role
      during zebrafish development.

PMID- 16456709
TI  - Mcl-1: a highly regulated cell death and survival controller.
AB  - Mcl-1 is one member of the Bcl-2 family that has a very short protein half-life.
      Since its identification in 1993, a great number of studies have implicated that
      Mcl-1 plays an important role in various cell survival pathways. However, not
      until recently did the molecular mechanism by which Mcl-1 antagonizes apoptosis
      have begun to be elucidated. Mcl-1 is rapidly degraded in response to cell death
      signals and is immediately re-induced by survival stimuli. These results indicate
      that Mcl-1 plays an apical role in many cell death and survival regulatory
      programs.

PMID- 16456710
TI  - The tumor suppressor DAP-kinase links cell adhesion and cytoskeleton
      reorganization to cell death regulation.
AB  - Death-associated protein (DAP)-kinase, an actin-cytoskeleton localized
      serine/threonine kinase, functions as a novel tumor suppressor and participates
      in a wide variety of cell death systems. Recent studies indicate that DAP-kinase
      elicits a potent cytoskeletal reorganization effect and is capable of modulating
      integrin inside-out signaling. Using this understanding of DAP-kinase protein
      function as a framework, we discuss the functional mechanisms of this kinase in
      regulating death-associated morphological and signaling events. Furthermore, a
      potential role of DAP-kinase to be a drug target is also discussed.

PMID- 16456711
TI  - Mitosin/CENP-F in mitosis, transcriptional control, and differentiation.
AB  - Mitosin/CENP-F is a large nuclear/kinetochore protein containing multiple leucine
      zipper motifs potentially for protein interactions. Its expression levels and
      subcellular localization patterns are regulated in a cell cycle-dependent manner.
      Recently, accumulating lines of evidence have suggested it a multifunctional
      protein involved in mitotic control, microtubule dynamics, transcriptional
      regulation, and muscle cell differentiation. Consistently, it is shown to
      interact directly with a variety of proteins including CENP-E, NudE/Nudel, ATF4,
      and Rb. Here we review the current progress and discuss possible mechanisms
      through which mitosin may function.

PMID- 16456712
TI  - Thioacetamide induced liver damage in zebrafish embryo as a disease model for
      steatohepatitis.
AB  - Steatohepatitis has recently been increasing as a cofactor influencing the
      progression of fibrosis, cirrhosis, adenoma and carcinoma in liver; however, the
      mechanisms by which it contributes to liver injury remain uncertain. We induced
      steatohepatitis in zebrafish embryos using thioacetamide (TAA). TUNEL assay
      revealed significant increasing of apoptosis in liver after 5 days post
      fertilization and the increasing of apoptosis was observed to be associated with
      the up-regulation of apoptotic genes such as, bad, bax, P-38a, caspase-3 and 8,
      and JNK-1. Histological sections by oil red O stain showed the accumulation of
      fatty droplets which causes the pushing of the nucleus towards one side. Up
      regulation of steatosis markers such as, ACC, adiponectin, PTL, CEBP- alpha and
      beta, SREBP-1 was also observed. Furthermore, the elevation of glutathione
      peroxidase in TAA treated embryos indicated that TAA induces lipid peroxidation
      which leads to causes liver damage. Zebrafish has already been considered as a
      good human disease model and in this context; TAA-treated zebrafish may serve as
      a good animal model to study the molecular pathogenesis of steatohepatitis.
      Moreover, non-availability of specific drugs to prevent steatohepatitis, this
      animal model may serve as a powerful preclinical platform to study the
      therapeutic strategies and for evaluating chemoprevention strategies for this
      disease.

PMID- 16456713
TI  - Recent progress in understanding the mechanism of P-glycoprotein-mediated drug
      efflux.
AB  - P-glycoprotein (P-gp) is an ATP-dependent drug pump that can transport a broad
      range of hydrophobic compounds out of the cell. The protein is clinically
      important because of its contribution to the phenomenon of multidrug resistance
      during AIDS/HIV and cancer chemotherapy. P-gp is a member of the ATP-binding
      cassette (ABC) family of proteins. It is a single polypeptide that contains two
      repeats joined by a linker region. Each repeat has a transmembrane domain
      consisting of six transmembrane segments followed by a hydrophilic domain
      containing the nucleotide-binding domain. In this mini-review, we discuss recent
      progress in determining the structure and mechanism of human P-glycoprotein.

PMID- 16456715
TI  - The effect of PS content on the ability of natural membranes to fuse with
      positively charged liposomes and lipoplexes.
AB  - Supramolecular aggregates containing cationic lipids have been widely used as
      transfection mediators due to their ability to interact with negatively charged
      DNA molecules and biological membranes. First steps of the process leading to
      transfection are partly electrostatic, partly hydrophobic interactions of
      liposomes/lipoplexes with cell and/or endosomal membrane. Negatively charged
      compounds of biological membranes, namely glycolipids, glycoproteins and
      phosphatidylserine (PS), are responsible for such events as adsorption,
      hemifusion, fusion, poration and destabilization of natural membranes upon
      contact with cationic liposomes/lipoplexes. The present communication describes
      the dependence of interaction of cationic liposomes with natural and artificial
      membranes on the negative charge of the target membrane, charges which in most
      cases were generated by charging the PS content or its exposure. The model for
      the target membranes were liposomes of variable content of PS or PG
      (phosphatidylglycerol) and erythrocyte membranes in which the PS and other
      anionic compound content/exposure was modified in several ways. Membranes of
      increased anionic phospholipid content displayed increased fusion with DOTAP (1,2
      dioleoyl-3-trimethylammoniumpropane) liposomes, while erythrocyte membranes
      partly depleted of glycocalix, its sialic acid, in particular, showed a decreased
      fusion ability. The role of the anionic component is also supported by the fact
      that erythrocyte membrane inside-out vesicles fused easily with cationic
      liposomes. The data obtained on erythrocyte ghosts of normal and disrupted
      asymmetry, in particular, those obtained in the presence of Ca(2+), indicate the
      role of lipid flip-flop movement catalyzed by scramblase. The ATP-depletion of
      erythrocytes also induced an increased sensitivity to hemoglobin leakage upon
      interactions with DOTAP liposomes. Calcein leakage from anionic liposomes
      incubated with DOTAP liposomes was also dependent on surface charge of the target
      membranes. In all experiments with the asymmetric membranes the fusion level
      markedly increased with an increase of temperature, which supports the role of
      membrane lipid mobility. The decrease in positive charge by binding of plasmid
      DNA and the increase in ionic strength decreased the ability of DOTAP
      liposomes/lipoplexes to fuse with erythrocyte ghosts. Lower pH promotes fusion
      between erythrocyte ghosts and DOTAP liposomes and lipoplexes. The obtained
      results indicate that electrostatic interactions together with increased mobility
      of membrane lipids and susceptibility to form structures of negative curvature
      play a major role in the fusion of DOTAP liposomes with natural and artificial
      membranes.

PMID- 16456714
TI  - Surviving high-intensity field pulses: strategies for improving robustness and
      performance of electrotransfection and electrofusion.
AB  - Electrotransfection and electrofusion, both widely used in research and medical
      applications, still have to face a range of problems, including the existence of
      electroporation-resistant cell types, cell mortality and also great batch-to
      batch variations of the transfection and fusion yields. In the present study, a
      systematic analysis of the parameters critical for the efficiency and robustness
      of electromanipulation protocols was performed on five mammalian cell types.
      Factors examined included the sugar composition of hypotonic pulse media
      (trehalose, sorbitol or inositol), the kinetics of cell volume changes prior to
      electropulsing, as well as the growth medium additives used for post-pulse cell
      cultivation. Whereas the disaccharide trehalose generally allowed regulatory
      volume decrease (RVD), the monomeric sugar alcohols sorbitol and inositol
      inhibited RVD or even induced secondary swelling. The different volume responses
      could be explained by the sugar selectivity of volume-sensitive channels (VSC) in
      the plasma membrane of all tested cell types. Based on the volumetric data,
      highest transfection and fusion yields were mostly achieved when the target cells
      were exposed to hypotonicity for about 2 min prior to electropulsing. Longer
      hypotonic treatment (10-20 min) decreased the yields of viable transfected and
      hybrid cells due to (1) the cell size reduction upon RVD (trehalose) or (2) the
      excessive losses of cytosolic electrolytes through VSC (inositol/sorbitol).
      Doping the plasma membrane with lipophilic anions prevented both cell shrinkage
      and ion losses (probably due to VSC inhibition), which in turn resulted in
      increased transfection and fusion efficiencies.

PMID- 16456716
TI  - A general channel model accounts for channel, carrier, counter-transport and co
      transport kinetics.
AB  - In this work we propose a unifying model of mediated membrane transport, based
      upon the idea that the integral membrane proteins involved in these processes
      operate via complex channel mechanisms. In the first part, we briefly review
      literature about the structural aspects of membrane transporters. We conclude
      that there is a substantial amount of evidence suggesting that most membrane
      proteins performing transport are embodied with channel-like structures that may
      constitute the translocation paths. This includes cases where the
      phenomenological transport kinetics do not correspond to the classical channel
      behavior. In the second part of this article we introduce the general channel
      model of mediated transport and employ it to derive specific examples, like
      simple one- or two-ligand channels, water-ligand channels, simple carriers, co-
      and counter-transport systems and more complex water-ligand carriers. We show
      that, for the most part, these particular cases can be obtained by the
      application of the techniques of diagram reduction to the full model. The
      necessary conditions for diagram reduction reflect physical properties of the
      protein and its surroundings.

PMID- 16456717
TI  - Functionally important residues in the predicted 3(rd) transmembrane domain of
      the type IIa sodium-phosphate co-transporter (NaPi-IIa).
AB  - The type IIa Na(+)/P(i), cotransporter (NaPi-IIa) mediates electrogenic transport
      of three Na(+) and one divalent P(i) ion (and one net positive charge) across the
      cell membrane. Sequence comparison of electrogenic NaPi-IIa and IIb isoforms with
      the electroneutral NaPi-IIc isoform pointed to the third transmembrane domain
      (TMD-3) as a possibly significant determinant of substrate binding. To elucidate
      the role of TMD-3 in the topology and mechanism underlying NaPi-IIa function we
      subjected it to cysteine scanning mutagenesis. The constructs were expressed in
      Xenopus oocytes and P(i) transport kinetics were assayed by electrophysiology and
      radiotracer uptake. Cys substitution resulted in only marginally altered kinetics
      of P(i) transport in those mutants providing sufficient current for analysis.
      Only one site, at the extracellular end of TMD-3, appeared to be accessible to
      methanethiosulfonate reagents. However, additional mutations carried out at D224
      (replaced by E, G or N) and N227 (replaced by D or Q) resulted in markedly
      altered voltage and substrate dependencies of the P(i)-dependent currents.
      Replacing Asp-224 (highly conserved in electrogenic a and b isoforms) with Gly
      (the residue found in the electroneutral c isoform) resulted in a mutant that
      mediated electroneutral Na(+)-dependent P(i) transport. Since electrogenic NaPi
      II transports 3 Na(+)/transport cycle, whereas electroneutral NaPi-IIc only
      transports 2, we speculate that this loss of electrogenicity might result from
      the loss of one of the three Na(+) binding sites in NaPi-IIa.

PMID- 16456719
TI  - Learning how membrane fatty acids affect cardiovascular integrity.

PMID- 16456720
TI  - Membrane basis for fish oil effects on the heart: linking natural hibernators to
      prevention of human sudden cardiac death.
AB  - The concept that diet-induced changes in membrane lipids could modify heart
      function partly arose from observations that membrane composition and physical
      properties were closely associated with the capacity of the heart to respond
      appropriately to torpor and hibernation. Observations of natural hibernators
      further revealed that behavior of key membrane-bound enzymes could be influenced
      through the lipid composition of the cell membrane, either by changing the
      surrounding fatty acids through reconstitution into a foreign lipid milieu of
      different composition, or by alteration through diet. Myocardial responsiveness
      to beta-adrenoceptor stimulation, including initiation of spontaneous dysrhythmic
      contractions, was altered by both hibernation and dietary modulation of membrane
      fatty acids, suggesting modified vulnerability to cardiac arrhythmia. Subsequent
      studies using whole-animal models recognized that vulnerability to ventricular
      fibrillation decreased as the polyunsaturated: saturated fat (P:S) ratio of the
      diet increased. However, dietary fish oils, which typically contain at least 30%
      saturated fatty acids and only 30% long-chain n-3 (omega-3) polyunsaturated fatty
      acids (PUFA), exhibit antiarrhythmic effects that exceed the predicted influence
      of the P:S ratio, suggesting properties unique to the long-chain n-3 PUFA. Large
      scale clinical trials and epidemiology have confirmed the arrhythmia prevention
      observed in vitro in myocytes, papillary muscles, and isolated hearts and in
      whole-animal models of sudden cardiac death. Some progress has been made towards
      a biologically plausible mechanism. These developments highlight nature's ability
      to provide guidance for the most unexpected applications.

PMID- 16456722
TI  - Antiarrhythmic mechanisms of n-3 PUFA and the results of the GISSI-Prevenzione
      trial.
AB  - The purpose of this paper is twofold: on the one hand, to confirm the positive
      results on n-3 PUFA from the overall results Gruppo Italiano per lo Studio della
      Sopravvivenza nell'Infarto Miocardico (GlSSI)-Prevenzione trial; on the other, to
      summarize and describe how the results of an important trial can help generate
      hypotheses either on mechanisms of action or on differential results in
      particular subgroups of patients, as well as test the pathophysiological
      hypotheses that have accompanied in the years the story of the hypothesized
      mechanisms of action of a drug. GISSI-Prevenzione was conceived as a pragmatic
      population trial on patients with recent myocardial infarction and it was
      conducted in the framework of the Italian public health system. In GISSI
      Prevenzione, 11,323 patients were enrolled in a clinical trial aimed at testing
      the effectiveness of n-3 polyunsaturated fatty acids (PUFA) and vitamin E.
      Patients were invited to follow Mediterranean dietary habits, and were treated
      with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA at 1
      g daily, but not vitamin E at 300 mg daily, was beneficial for death and for
      combined death, non-fatal myocardial infarction, and stroke. All the benefit,
      however, was attributable to the decrease in risk for overall (-20%),
      cardiovascular (-30%), and sudden death (-45%). At variance from the orientation
      of a scientific scenario largely dominated by the "cholesterol-heart hypothesis",
      GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol
      lowering effect) as a relevant pharmacological treatment for secondary prevention
      after myocardial infarction.

PMID- 16456721
TI  - Omega-3 fatty acids and the regulation of expression of endothelial pro
      atherogenic and pro-inflammatory genes.
AB  - By partially replacing the corresponding omega-6 analogues in membrane
      phospholipids, omega-3 fatty acids have been shown to decrease the
      transcriptional activation of genes--e.g., adhesion molecules, chemoattractants,
      inflammatory cytokines--involved in endothelial activation in response to
      inflammatory and pro-atherogenic stimuli. This regulation occurs, at least in
      part, through a decreased activation of the nuclear factor-kappaB system of
      transcription factors, secondary to decreased generation of intracellular
      hydrogen peroxide. Such regulation by omega-3 fatty acids is likely linked to the
      presence of a higher number of double bonds in the fatty acid chain in omega-3
      compared with omega-6 fatty acids. By similar mechanisms, omega-3 fatty acids
      have been recently shown to reduce gene expression of cyclooxygenase-2, an
      inflammatory gene involved, through the activation of some metalloproteinases, in
      plaque angiogenesis and plaque rupture. The quenching of gene expression of pro
      inflammatory pro-atherogenic genes by omega-3 fatty acids has consequences on the
      extent of leukocyte adhesion to vascular endothelium, early atherogenesis and
      later stages of plaque development and plaque rupture, ultimately yielding a
      plausible comprehensive explanation for the vasculoprotective effects of these
      nutrients.

PMID- 16456723
TI  - Membrane effects of the n-3 fish oil fatty acids, which prevent fatal ventricular
      arrhythmias.
AB  - Fish oil fatty acids are known to exert beneficial effects on the heart and
      vascular systems. We have studied the membrane effects on ion channel conductance
      by the n-3 fish oil fatty acids that account for these beneficial effects. We
      have confirmed that these fatty acids prevent fatal cardiac arrhythmias in a
      reliable dog model of sudden cardiac death. This finding was followed by
      experiments indicating that the n-3 fatty acids electrically stabilize heart
      cells and do so largely through modulation of the fast voltage-dependent Na(+)
      currents and the L-type Ca(2+) channels in a manner, which makes the heart cells
      resistant to arrhythmias. Others and we have demonstrated that these membrane
      effects on the heart can prevent fatal cardiac arrhythmias in humans.

PMID- 16456724
TI  - The antiarrhythmic effect of n-3 polyunsaturated fatty acids: modulation of
      cardiac ion channels as a potential mechanism.
AB  - Sudden cardiac death remains one of the most serious medical challenges in
      Western countries. Increasing evidence in recent years has demonstrated that the
      n-3 polyunsaturated fatty acids (PUFAs) can prevent fatal ventricular arrhythmias
      in experimental animals and probably in humans. Dietary supplement of fish oils
      or intravenous infusion of the n-3 PUFAs prevents ventricular fibrillation caused
      by ischemia/reperfusion. Similar antiarrhythmic effects of these fatty acids are
      also observed in cultured mammalian cardiomyocytes. Based on clinical
      observations and experimental studies in vitro and in vivo, several mechanisms
      have been postulated for the antiarrhythmic effect of the n-3 PUFAs. The data
      from our laboratory and others have shown that the n-3 PUFAs are able to affect
      the activities of cardiac ion channels. The modulation of channel activities,
      especially voltage-gated Na(+) and L-type Ca(2+) channels, by the n-3 fatty acids
      may explain, at least partially, the antiarrhythmic action. It is not clear,
      however, whether one or more than one mechanism involves the beneficial effect of
      the n-3 PUFAs on the heart. This article summarizes our recent studies on the
      specific effects of the n-3 PUFAs on cardiac ion channels. In addition, the
      effect of the n-3 PUFAs on the human hyperpolarization-activated cyclic
      nucleotide-modulated channel is presented.

PMID- 16456725
TI  - Is fish oil good or bad for heart disease? Two trials with apparently conflicting
      results.
AB  - Two successive randomized trials examined the effect of an increased intake of
      fatty fish, or the use of fish oil supplements, in reducing mortality in men with
      heart disease. The Diet and Reinfarction Trial (DART) was conducted in 2033 men
      who were recovering from acute myocardial infarction (MI). Those who were advised
      to eat fatty fish (or who opted to take fish oil capsules instead) had a 29%
      reduction in all-cause mortality over the following two years compared with those
      not so advised. The effect appeared in the first few months of the trial. The
      Diet and Angina Randomized Trial (DART 2) involved 3114 men with stable angina.
      Advice to eat fatty fish did not reduce mortality, and taking fish oil capsules
      was associated with a higher risk of cardiac and sudden death. The adverse
      effects of fish or fish oil were restricted to men not taking beta-blockers or
      dihydropyridine calcium-channel blockers, and were greater in those taking
      digoxin. Evidence from other sources strongly suggests an anti-arrhythmic action
      of fish oil, particularly after MI or in the presence of acute ischemia. The
      apparently conflicting results of the two trials may reflect different actions of
      n-3 fatty acids in acute and chronic conditions, together with different effects
      of eating fish and taking fish oil capsules. A mechanism is proposed that could
      account for these findings.

PMID- 16456726
TI  - From fat to fat-1: a tale of omega-3 fatty acids.

PMID- 16456727
TI  - Affect regulation and temperament in children with Autism Spectrum Disorder.
AB  - Affect regulation (AR) and temperament were examined in children with Autism
      Spectrum Disorder (ASD). To determine AR, children were exposed to a mildly
      frustrating situation. Temperament was assessed by the Children's Behavior
      Questionnaire (CBQ). Children with ASD showed greater variability in AR and used
      less effective AR strategies compared to controls. Lower academic ability was
      associated with less effective AR strategies for the ASD while for the controls
      older age predicted more effective AR strategies. Those with ASD were lower than
      controls in Attention Focusing, Inhibitory Control, and Soothability. Of the
      three overarching temperament factors of the CBQ, only Effortful Control but not
      Negative Affectivity and Surgency/Extraversion distinguished those with ASD from
      controls. For the ASD group, higher academic ability predicted higher Negative
      Affectivity. Fewer symptoms and older chronological age predicted higher
      Effortful Control.

PMID- 16456728
TI  - Sex, touch, and HIV risk among ecstasy users.
AB  - We examined HIV risk among heavy and nonheavy ecstasy users, focusing
      specifically on touch and sexual behavior as part of the ecstasy experience.
      Structured interviews were conducted with 268 young adult (age 18-25) ecstasy
      users in Atlanta, Georgia. Heavy ecstasy users were more likely to have been
      tested for HIV than nonheavy users (79 vs. 68%). However, they also were more
      likely to perceive no chance of contracting HIV (36 vs. 26%). Touch, both sensual
      and sexual, was a significant part of the ecstasy experience. In addition,
      ecstasy use seemed to increase the sexual desire, however, not the ability to
      achieve an orgasm. Heavy users reported more sexual risk-taking than their
      nonheavy using counterparts. Results suggest that the setting of ecstasy use also
      may influence involvement in risk behaviors. Future longitudinal studies are
      needed on the relationship between ecstasy use, touch, sexual arousal and
      ability, and risk behavior.

PMID- 16456729
TI  - Impact of marriage on HIV/AIDS risk behaviors among impoverished, at-risk
      couples: a multilevel latent variable approach.
AB  - Studies among normative samples generally demonstrate a positive impact of
      marriage on health behaviors and other related attitudes. In this study, we
      examine the impact of marriage on HIV/AIDS risk behaviors and attitudes among
      impoverished, highly stressed, homeless couples, many with severe substance abuse
      problems. A multilevel analysis of 368 high-risk sexually intimate married and
      unmarried heterosexual couples assessed individual and couple-level effects on
      social support, substance use problems, HIV/AIDS knowledge, perceived HIV/AIDS
      risk, needle-sharing, condom use, multiple sex partners, and HIV/AIDS testing.
      More variance was explained in the protective and risk variables by couple-level
      latent variable predictors than by individual latent variable predictors,
      although some gender effects were found (e.g., more alcohol problems among men).
      The couple-level variable of marriage predicted lower perceived risk, less
      deviant social support, and fewer sex partners but predicted more needle-sharing.

PMID- 16456730
TI  - Distribution of Bcl-2 gene expression and its prognostic value in non-small cell
      lung cancer.
AB  - The aim of this study was to determine the expression of Bcl-2 gene and
      prognostic importance of Bcl-2 expression in paraffin embedded blocks of patients
      diagnosed with non-small cell lung cancer (NSCLC). This study included the
      retrospective analysis of overall 46 patients diagnosed with NSCLC in our clinic
      between 1996 and 1999. In 16 (34.8%) patients, the diagnosis was made on biopsy
      of bronchial mucosa and in 30 (65.2%) patients, on materials obtained by surgical
      resection (lobectomy and pneumonectomy). We reviewed the sections 4-6 microns in
      size and stained with Hemotoxylin-Eosine (HE) obtained from paraffin embedded
      blocks and fixed by 10% formalin. These sections are transferred on to slides
      covered with poly-L-lysine, then de-paraffinization was made. In all cases,
      immunohistochemical staining with Bcl-2 antibodies was performed. Positive
      staining was observed in 9 (19.6%) patients, but not in 37 (80.4%) patients. Out
      of 32 cases with squamous cell tumor, 8 (25%) were observed to have positive
      staining in their sections, but 24 (75%) were not so. No staining was observed in
      11 cases whose cell type was adenoma and two cases whose cell type was
      adenosquamos (100%). Staining was present in the section of one case with large
      cell (100%). Median survival time was 36.6 months in cases in which staining was
      observed and 6.10 months in cases in which staining was not observed, with a
      significant difference (p< 0.05). In conclusion, the rate of survival was higher
      in cases in which staining was present.

PMID- 16456731
TI  - [Nutritional status, pulmonary functions, and exercise performance in COPD
      cases].
AB  - The aim of this study was evaluation of nutritional status in attack and stable
      chronic obstructive pulmonary disease (COPD) cases, and investigating the
      relation between nutrition parameters and pulmonary functions, exercise
      performance and general healthy status. Anthropometric measures of 10 cases with
      attack (group 1), 14 stabilized COPD cases (group 2) and 10 control cases (group
      3) were evaluated by measuring serum albumin, transferrin, tumor necrosis factor
      alpha (TNF-alpha) levels, and fat-free mass (FFM) levels. Six minutes walking
      test (mwt) and SGRQ questionnaire were performed. Body mass index (BMI) of group
      1 and 2 were significantly lower than group 3 (p= 0.023, p= 0.008, respectively).
      Albumin levels were significantly lower in group 1 than group 2 (p< 0.001) and 3
      (p= 0.001). Levels of transferrin were significantly lower in group 1 compared
      with group 3 (p= 0.015). TNF-alpha levels were significantly high in group 1
      compared with group 2 (p= 0.002), and high in group 2 compared with group 3 (p=
      0.001). FFM was significantly low in group 1 compared with group 2 (p= 0.003),
      and low in group 2 compared with group 3 (p< 0.001). Mean distance of 6 mwt was
      225.80 +/- 40.35 m in group 1, it was 405.16 +/- 95.51 m in group 2 (p< 0.001). A
      positive relation was seen between FFM and BMI, 6 mwt (p= 0.006, r= 0.481 ve p<
      0.001, r= 0.830, respectively), between albumin levels and 6 mwt (p< 0.001, r=
      0.850). A negative correlation was observed between TNF-alpha and 6 mwt (p<
      0.001, r= -0.745). There was no statistical difference in antropometric measures
      between groups. Total score and daily life were statistically high in group 1
      than group 2 (p= 0.009, p= 0.013). Although no changes was seen in antropometric
      measures of COPD cases, a nutritional defect was seen and a significant relation
      was observed between nutrition parameters and effort capacity.

PMID- 16456732
TI  - [Evaluation of dynamic hyperinflation parameters and exercise capacity at maximal
      exercise in patients with COPD].
AB  - Hyperinflation is an important limiting factor for exercise performance in
      patients with chronic obstructive pulmonary disease (COPD). Hyperinflation can be
      determined by measuring residual volume (RV), functional residual capacity (FRC),
      and total lung capacity (TLC) at rest, and by measuring inspiratory capacity (IC)
      and end-expiratory lung volume (EELV) at maximal exercise. This study aimed to
      evaluate changes in hyperinflation parameters on maximal exercise in subjects
      with COPD. Patients with clinically stable COPD (n= 43) and healthy controls (n=
      14) were included. Subjects performed pulmonary function tests and an incremental
      exercise test on cycle ergometry. Statistically significant differences (p< 0.05)
      were found regarding exercise test parameters including exercise duration,
      maximum oxygen uptake, breathing reserve, maximum minute ventilation, and
      breathing pattern between groups. There was significant increase in EELV (p<
      0.05) and decrease in IC (p< 0.05) at maximum exercise when hyperinflation
      parameters were compared at baseline and maximum exercise. Our results showed
      that hyperinflation was evident at maximal exercise, although there were no
      hyperinflation findings at rest in subjects with COPD. We believe that in
      patients with COPD, it is better to evaluate hyperinflation at maximal exercise
      than at rest.

PMID- 16456733
TI  - The relationship between pulmonary function tests, thorax HRCT, and quantitative
      ventilation-perfusion scintigraphy in chronic obstructive pulmonary disease.
AB  - We have evaluated the relationship between pulmonary function tests (PFT), thorax
      high resolution computed tomography (HRCT) images and quantitative ventilation
      perfusion (V/Q) scintigraphic studies in 16 male patients (mean age 65.6 +/- 5.5
      years) with chronic obstructive pulmonary disease (COPD). The mean forced vital
      capacity (FVC) value of the patient group was 2352 +/- 642 mL (65.4 +/- 15.8%),
      whereas mean forced expiratory volume in one second (FEV(1)) was found to be 1150
      +/- 442 mL (40.8 +/- 14.9%). The ratio of carbon monoxide diffusion capacity to
      alveolar ventilation (DLCO/VA) was 3.17 +/- 0.88 mL/min/mmHg/L, and the mean
      partial oxygen (PaO(2)) and carbon dioxide (PaCO(2)) pressures were 68.5 +/-
      11.04 mmHg and 38.9 +/- 5.8 mmHg respectively. For each patient, thorax HRCT and
      V/Q scintigraphic images of both lungs were divided into upper, mid and lower
      zones during examination. Visual scoring for the assessment of emphysema on
      thorax HRCT were used and images were graded from mild to severe (< or = 25% - >
      or = 76%). Emphysema scores were found to be higher on upper zones with
      accompanying lowest V/Q ratios. DLCO/VA, DLCO, total emphysema scores, and
      individual emphysema scores of the upper, mid and lower zones were found to be
      correlated. As a conclusion, it can be stated that emphysematous changes in COPD
      patients are more apparent in the upper lung zones, which also have the lowest
      V/Q ratios.

PMID- 16456735
TI  - [Knowledge and attitude of workers and patrons in coffee houses, cafes,
      restaurants about cigarette smoke].
AB  - A legislation about smoking restriction in all workplaces is under consideration
      in Turkey. In our study we evaluated the knowledge and attitudes of workers and
      patrons of cafes, restaurants and coffee houses about smoking ban in their work
      places. Twenty eight owners, 67 workers and 242 patrons in 12 coffee house, 12
      restaurants and 7 cafes were interviewed. A desire to work in a smoke-free
      workplace was most frequent (79.8%) among coffee house group and 63.9% in cafe
      group, 57.8% in restaurants group. Smoking ban was most frequently requested by
      coffee house group and least frequently by cafe group. Coffee house and cafe
      groups were supposing a decrease in the number of patrons and incomes with such a
      legislation, whereas restaurant group was thinking that no change will occur.
      45.4% of the coffee house patrons stated that they would less frequently visit
      that workplace in case of a smoking ban, whereas 47.8% of restaurant patrons
      stated that there would be no change with their frequency to visit there. A
      desire to work in a smoke-free workplace and requesting a smoking ban for all
      workplaces were more frequent among nonsmokers. Smokers stated that their
      frequency to visit those places would decrease in case of a smoking ban, whereas
      nonsmokers stated an increase in their frequency to visit those places. We think
      that informing the owners and workers of coffee houses, restaurants and cafes
      about these facts is very important and would increase the compliance to such a
      legislation.

PMID- 16456734
TI  - [The comparison of nicotine replacement therapy and behavioral education in
      smoking cessation: a study of naturalistic follow-up].
AB  - In this study, we aimed to compare quitting smoking rates after behavioral
      education (BE) and/or nicotine replacement therapy (NRT). 610 patients applied
      between October 1999-April 2002 have been acknowledged and evaluated by a
      questionnaire including demographic variables, smoking history, smoking habits
      and attitudes, motivation; biochemical assay and spirometric measures were
      examined. One-year follow-up results and demographic variables of patients who
      recruited to treatment (n= 435) were analyzed by chi-square, Student-t test, one
      way ANOVA and post-hoc tests. 375 (66.8 %) case were given NRT and BE; only BE
      (Fagerstrom < 6, not want to use of NRT, medical and economic reasons) was
      recommended to 186 (33.2 %) case. There was not difference between NRT and BE
      groups with regards to age, sex, packet year, smoking beginning age except
      Fagerstrom score. Smoking cessation rates for 1-year were 31.5 % in NRT group,
      24.2 % in BE group, and 29.1 % in whole group (x(2)= 3.19, p> 0.05). Quitting
      rates were similar between age, sex, education, occupation, and complaint groups.
      Two groups were not statistically different with regards of smoking history and
      nicotine dependence. The most frequent side effect was skin reactions (7 %). The
      economical and medical burden of smoking increase as time goes on. According to
      our results, NRT and behavioral education are both efficient in smoking
      cessation.

PMID- 16456736
TI  - [The prevalence of occupational asthma in auto and furniture dye workers in
      downtown Elazig].
AB  - Occupational asthma (OA) is characterized by reversible airway obstruction and/or
      bronchial hyperresponsiveness occurred after exposition to dust, vapor, gas or
      smoke which are present in the workplace. We aimed to determine the frequency of
      OA in auto and furniture dye workers in our city center. One-hundred-forty-two
      workers in Elazig Central Industrial Centre (86 auto, 56 furniture dyes) were
      included in the study. The workers were questioned with "Turkish Thorax
      Association Occupational and Environmental Pulmonary Diseases Evaluation Form",
      and physical examination and pulmonary function tests (PFT) were performed.
      Follow of peak expiratory flow rate (PEFR) and reversibility tests were performed
      to patients who had complaints or abnormality in PFT. The workers who had
      reversibility and positive daily PEFR variability were taken away from work and
      PEFR variables were followed. The workers had no symptoms when they were taken
      away from work and daily PEFR were below than 20%, accepted as OA. Twenty-one
      workers of 22 workers who have abnormal questionnaire, symptoms and abnormality
      in PFT, accepted daily PEFR measurements. Daily PEFR variability and
      reversibility test were positive in 5 (3.52%) workers who were accepted as OA. We
      detected the prevalence of OA, an important worker health problem, was 3.52% in
      auto and furniture dyes in industrial centre of our city. We think that the
      prevalence of OA can be determined with detailed history, serial PEFR follow and
      using PFT, in the absence of specific bronchial provocative tests. Thus, it is
      important to be become conscious about OA the groups who are under risk.

PMID- 16456737
TI  - [Prevalence of habitual snoring and sleep-disordered breathing in primary school
      children in Afyonkarahisar].
AB  - Obstructive sleep apnea syndrome affects 0.7-3% of children and snoring is an
      important symptom. We aimed to evaluate the prevalence of habitual snoring and
      sleep-disordered breathing in primary school students in Afyonkarahisar city.
      There are 41 primary schools in uc education regions in Afyonkarahisar city. One
      school from each region was randomly selected and all the students in that school
      were given a questionnaire. Of the 1100 given questionnaires 786 (71.5%) were
      filled in adequately and were accepted for evaluation. Of the students 407
      (51.8%) were girls and 379 (48.2%) were boys. Mean age was 9.9 +/- 2.0 (7-15).
      The prevalence of habitual snoring was found as 4.8%. With regard to gender,
      occasional snoring and habitual snoring was significantly more prevalent than
      never snoring in boys. The prevalence of sleep disordered breathing symptoms was
      found to be significantly higher in habitual snorers. Maternal and paternal
      smoking frequency and passive smoke exposure was more common in habitual snorers
      but there were no significant differences among the groups. Hyperactivity
      symptoms were significantly higher in habitual snorers. In our study, school
      performance was found to be 10.9 folds lower in habitual snorers than non
      snorers. We think that questioning the obstructive sleep apnea syndrome symptoms
      in children and performing diagnostic procedures and treatment when suspected
      will decrease the morbidity.

PMID- 16456738
TI  - Metastatic lung cancer: presenting with ocular symptoms.
AB  - A 48 year-old man, without any systemic disease, was admitted to our hospital
      with a complaint of decreased visual acuity and pain in his left eye. The orbital
      magnetic resonance imaging revealed metastatic lesions and further evaluations
      disclosed a primary lung cancer.

PMID- 16456739
TI  - Spontaneous sternoclavicular joint infection.
AB  - Spontaneous infection of the sternoclavicular joint (SCJ) is an uncommon clinical
      entity. There are only few reports about this entity in the literature. Various
      risk factors are found to be associated with SCJ infection but rarely no risk
      factors can be detected. As a result of its rarity and confusing with
      malignancies, the description of this condition is primarily in the form of case
      reports and small series in the literature. Besides, optimal therapy has not been
      described definitely. We present a case of spontaneous SCJ infection treated
      successfully by drainage and the use of nonsteroidal antiinflammatory drug.

PMID- 16456740
TI  - Recurrent pneumothorax at an infant with miliary tuberculosis.
AB  - A seven-month-old girl with miliary tuberculosis (Tbc) admitted to hospital due
      to development of acute dyspnoea and cyanosis at the end of third month of anti
      Tbc therapy. Pneumothorax was evident at right lung with the chest radiography. A
      chest tube placed under water seal was applied. The patient healed up and then
      discharged. One week later, the patient admitted to hospital again, with same
      complaints due to pneumothorax at the same hemithorax. Same treatment was applied
      to the patient. Anti-Tbc therapy was stopped at the end of 12th month. Although,
      pneumothorax is a rare life-threatening complication of miliary Tbc, it's not
      seen only on admission or soon after beginning of the therapy, but it can be seen
      several months later during treatment. We want to report this case. That is the
      first case in which pneumothorax developed during therapy of an infant with
      miliary Tbc.

PMID- 16456741
TI  - [Pleural empyema due to Salmonella typhi].
AB  - 65 years old female was admitted to hospital with fever, purulent sputum and
      dyspnea. The patient has hepatic cirrhosis secondary to autoimmune hepatitis and
      hepatocellular carcinoma. Immunosuppressive treatment is used for autoimmune
      hepatitis. In physical examination matute and diminished respiratory sounds were
      determined at right hemithorax. Ascitis was determined in abdominal examination.
      Chest X-ray showed pleural effusion in right hemithorax. Serohemorrhagic fluid
      was aspirated by thoraco-synthesis. Pleural fluid pH was 6.9 and had an exudative
      nature. The patient was the diagnosed as empyema. Right tube thoracostomy was
      performed and sulbactam-ampicillin 6 g/day therapy was started. In patient's
      ascite fluid no bacteria and leucocytes was seen. Salmonella typhi was isolated
      from pleural fluid. No microorganisms were isolated from ascite fluid, urine and
      stool culture. Klebsiella pneumoniae is isolated in patient's hemoculture.
      Clinical improving was detected. Chest X-ray showed total regression of pleural
      fluid and the tube thoracostomy removed. We presented this case because of rarely
      seen microorganism (S. typhi) in immunocompromised patients a cause of pleural
      empyema which is frequently seen gastrointestinal infections.

PMID- 16456742
TI  - [The superiorities of invasive procedures in nodal staging of non-small cell lung
      cancers].
AB  - The staging of non-small cell lung cancer is the most important factor that
      affects the treatment form and prognosis. The management strategy includes
      serious variations according to clinical condition of the patient, preoperative,
      intraoperative and postoperative pathologic staging outcomes. Today, obtaining
      the histopathological diagnosis preoperatively became mandatory. Reaching the
      definite tissue diagnosis requires the using of invasive technics. Nowadays;
      there is a widespread use of invasive staging and diagnostic procedures in order
      to show the evidence of disease presence and determine the probability of
      contralateral metastasis in a patient who will undergo a possible thoracotomy. In
      the preoperative period, benefiting from the invasive staging methods that will
      reveal occult N2 disease totally, would be more useful for the patients.

PMID- 16456743
TI  - [Smoking restrictions in restaurants].

PMID- 16456744
TI  - [Aeromedical evacuation of critically ill and injured patients].
AB  - The mission of aeromedical evacuation of patients, whether in peacetime, wartime
      or under unexpected conditions (earthquake, flood etc) will remain the same.
      Aeromedical evacuation systems have become an integral part of the practice of
      critical care medicine. These systems provide interhospital transport of
      critically ill or severely injured patients. Understanding the medical aspects of
      flights and the capabilities of the aeromedical environment will help to evacuate
      patients in a safe and a proper manner.

PMID- 16456745
TI  - An ultrastructural study on indirect trauma of dental pulp caused by
      maxillofacial impact injury in dogs.
AB  - BACKGROUND: Indirect injuries of adjacent tissues and organs usually accompany
      maxillofacial impact injuries. However, studies on indirect dental pulp injury
      are rare. This study was designed to determine the characteristics of indirect
      dental pulp injury caused by impact injury of mandible in dogs. METHODS: Eighteen
      dogs were divided equally into six groups with random allocation. Right mandible
      of each dog was impacted but teeth were not injured directly. Then, the animals
      were killed at appointed time points and ultrastructural changes in dental pulp
      of assigned teeth of each dog were investigated with transmission electron
      microscope. RESULTS: Dental pulp of the fourth premolar of right mandible was
      injured very severely, but irreversible necrosis did not occur in the end. Dental
      pulp of the second premolar of right mandible was injured less severely and
      reversibly. Dental pulp of the second premolar of left mandible was injured
      mildly and temporarily. CONCLUSION: In the indirect injury of dental pulp caused
      by maxillofacial impact injury, the injured area is relatively extensive. The
      effect of the trauma decreases progressively and sharply as the distance to the
      impact site increases. Ultrastructural changes in the damaged nerves take place
      early.

PMID- 16456746
TI  - [Early enteral and glutamine enriched enteral feeding ameliorates healing of
      colonic anastomosis: experimental study].
AB  - BACKGROUND: To investigate the effects of postoperative early enteral and
      glutamine enriched enteral feeding on the healing of experimental colonic
      anastomosis. METHODS: Forty Wistar-albino rats were equally divided into 4
      groups. Colonic transsection and anastomosis situated at the distal left colon
      was performed on all animals. Animals in groups 1 and 2 received late total
      enteral nutrition (TEN) and in groups 3 and 4 early TEN. Glutamine was added to
      TEN protocol in groups 2 and 4. The colonic segment including the anastomosis was
      excised at the end of the 7th day postoperatively. Bursting pressure of the
      anastomosis and tissue hydroxyproline levels were determined. RESULTS: Bursting
      pressure levels were 111.6 and 95.8 centimeters of water (cmH(2)O) in early and
      late nutrition groups, respectively (p=0.022). Comparison of late TEN groups
      showed a significant difference in favor of group with glutamine (95.8 vs 138.5
      cmH(2)O; p<0.0001). Highest bursting pressures (139 and 138.5 cmH(2)O) were
      measured in both early and late TEN groups with glutamine. Tissue hydroxyproline
      level in early TEN group (2440.3 microg) was significantly higher than late TEN
      group (1509.6 microg; p=0.024). Comparison of late TEN groups showed a
      considerable but not statistically significant difference (p=0.276) in favor of
      group with glutamine (1509.6 vs 1981.6 microg). CONCLUSION: Postoperative early
      TEN significantly ameliorates the resistance of the anastomosis and collagen
      synthesis. Glutamine enrichment in nutritional protocol decreases and reverses
      the disadvantages of late TEN regarding the resistance of anastomosis. A
      similarly positive, albeit weaker, effect of glutamine supplementation is also
      seen on collagen synthesis.

PMID- 16456747
TI  - [Neurogenic pulmonary edema: a prospective study based on observation].
AB  - BACKGROUND: In this study, we evaluated the cause and the clinical course of
      neurogenic pulmonary edema which has developed abruptly in some of the patients
      in the neurosurgical intensive care unit. METHODS: We evaluated 223 patients in
      the neurosurgical ICU (116 males; 107 females; mean age 44.4+/-19.5). Five of
      these had worsening in neurological evaluation and oxygenation and were diagnosed
      as having a neurogenic pulmonary edema. Patients with pneumonia were excluded
      from the study. RESULTS: We identified acute hydrocephaly in three patients and
      re-bleeding of an aneurysm in one as the cause of neurogenic pulmonary edema. No
      cause could be identified in the remaining patient. Although four patients could
      be discharged from the ICU, one died due to multiorgan failure. CONCLUSION:
      Physicians should be careful about neurogenic pulmonary edema, a life-threatening
      clinical condition, that develops within hours of a neurologic event and usually
      resolves with neurologic recovery.

PMID- 16456748
TI  - [Acute necrotizing pancreatitis: the results of the management of 38 patients].
AB  - BACKGROUND: We evaluated the patients who underwent surgical or nonoperative
      treatment for acute necrotizing pancreatitis. METHODS: The study included 38
      patients (22 males, 16 females; mean age 51.3 years; range 16 to 79 years) with
      acute necrotizing pancreatitis. Surgical treatment was performed in 23 patients,
      while 15 patients were treated conservatively. RESULTS: Gallstone (in 17
      patients) was the most common cause of pancreatitis. Twenty-five patients had
      sterile necrotizing pancreatitis, while 13 patients had infected necrotizing
      pancreatitis. Fifteen of the 25 cases with sterile necrosis were treated
      conservatively. The other 10 patients were initially treated by conservative
      methods, and were later treated surgically (due to six incorrect diagnosis, three
      organ failures, and one symptomatic pseudocyst). We applied continuous lavage to
      six of those patients and conventional drainage to four of them. Mortality rate
      was 23.7% globally; 24.0% in the sterile necrosis group and 23.1% in the infected
      necrosis group. Mortality rate was 21.7% in the surgical treatment group, and
      26.7% in the conservative treatment group. There were no statistically
      significant differences between those groups (p>0.05). Eleven of the 29 patients
      who survived had some complications. CONCLUSION: The management of sterile
      pancreatic necrosis is still a matter of debate. Most patients with sterile
      necrosis can be treated with conservative methods. Indication for surgery in
      sterile necrosis should be based on persisting or advancing organ complications
      and sepsis signs despite intensive care therapy. The patients with infected
      necrosis should be treated surgically. Surgical intervention is best deferred
      until the demarcation of necrosis is complete.

PMID- 16456749
TI  - [Evaluation of surgical methods in patients with blunt liver trauma].
AB  - BACKGROUND: We evaluated the surgical methods, morbidity and mortality in
      patients who had surgery for blunt liver trauma. METHODS: We retrospectively
      reviewed 159 patients (116 males, 43 females; mean age 33.6; range 15 to 67
      years) with blunt hepatic trauma regarding the cause and severity of liver
      injury, diagnostic procedures, associated injuries, management, morbidity, and
      mortality. Simple hepatorrhaphy was done in minor liver injuries (Grade I, II).
      To manage severe liver trauma (Grade III-V), debridement, selective hepatic
      artery ligation and omentum packing of the laceration (DSO) in 40; resectional
      debridement (RD) with direct control of bleeding vessels within the liver by the
      Pringle maneuver in 12; deep matress suture (DMS) in 23; and perihepatic packing
      (PP) in 9 patients were performed. RESULTS: The causes of trauma were motor
      vehicle accidents in 102, falls from height in 43 and violence induced blunt
      trauma in 14 patients. Among 159 patients, 84 had severe liver injuries and 75
      had minor liver injuries. Associated organ injuries were present in 104 patients
      and splenic injury was the most common. Mean units of blood transfusions in DSO,
      DMS, RD and PP were 4.3, 6.2, 5.5 and 9.5 respectively. Mean time for liver
      surgery in DSO, RD, DMS and PP were 34.7, 38.1, 26 and 18.2 minutes respectively.
      Morbidity rate was higher in DMS group than in DSO and RD groups, and the
      difference was statistically significant (p<0.001). Twenty-five patients (29.4%)
      died of severe liver injuries and 9 (12%) died of minor liver injuries. The
      overall mortality rate was 21.3%. CONCLUSION: DSO, and RD methods don't increase
      operation time and amount of blood transfusion. They cause less morbidity and
      mortality when compared to DMS.

PMID- 16456751
TI  - An evaluation of individual plain abdominal radiography findings in pediatric
      appendicitis: results from a series of 424 children.
AB  - BACKGROUND: This study was conducted to collect the results of the plain
      abdominal radiography (PAR) signs, to determine their individual diagnostic
      values, and to discuss them under a brief literature review. METHODS: Eight
      predetermined PAR signs were individually interpreted in a series of 424
      consecutive children (278 males; 146 females; median age 10 years; range 11
      months to 17 years) who underwent an operation for appendicitis. The sensitivity,
      specificity, and positive and negative predictive values for the signs were
      determined. RESULTS: Appendicitis was confirmed in 378 (89%) patients. Among the
      remaining 46 (11%) patients with a normal appendix, 20 (5%) had other
      intraabdominal pathologies. Calcified fecalith, mass image in right-lower
      quadrant (RLQ), psoas obscuration, and localized extraluminal air signs were all
      highly specific and therefore, unlikely to be present if the appendix is normal.
      On the other hand, the sensitivity values were low, in general, for all the PAR
      signs investigated. Yet, presence of dilated transverse colon and/or single air
      fluid level in the RLQ has the highest percentage occurrence with appendicitis.
      CONCLUSION: Although the there is no single PAR finding capable of ruling the
      diagnosis of appendicitis out, basic knowledge on PAR findings could have an
      impact on decision making process for clinicians dealing with pediatric acute
      abdominal pain.

PMID- 16456750
TI  - Noninvasive management strategy in hemodynamically unstable patients with blunt
      trauma.
AB  - BACKGROUND: Non-operative management in abdominal injuries may reduce non
      therapeutic laparatomies without increasing mortality. The aim of this study is
      to evaluate the results of a recently used non-invasive management strategy, in
      trauma patients in our institution. METHODS: A retrospective chart review was
      performed. The sixty-three patients (50 males; 13 females; range 8 to 61 years)
      with abdominal injuries who were unstable during their admissions to our
      institution between July 1st, 2000 and July 1st, 2001 (the first year of the NIMS
      implementation) were identified and divided into three groups according to the
      presence or absence of surgical intervention and the timing of the operation.
      RESULTS: There were 63 blunt abdominal trauma patients who were unstable during
      admission. Patients in Group 1 (n=14) and Group 2 (n=10) had urgent laparotomy
      during the resuscitation therapy or after a median observation period of 7 hours
      (range, 2 to 20). Group 3 patients (n=39) did not require surgical intervention.
      CONCLUSION: Most of the trauma patients who respond to initial fluid replacement
      do not require surgery. Close monitoring and repeated abdominal examinations
      (NIMS) can be the main criteria for surgical intervention, although they are not
      the most reliable techniques in the diagnosis of solid organ injuries in all
      patients and of hollow organ injuries in conscious patients.

PMID- 16456752
TI  - [Assessment of physicians employed in emergency medical services about their
      level of knowledge on basic life support, advanced cardiac life support and
      medicolegal responsibilities].
AB  - BACKGROUND: We aimed to determine the level of knowledge of Emergency Medical
      Services (EMS) physicians on Basic Life Support (BLS), Advanced Cardiac Life
      Support (ACLS) and medicolegal responsibilities in conjunction with related
      factors. METHODS: Fifty-three physicians (43 male, 10 females; mean age 39 years;
      range 28 to 50 years) employed in EMS were required to respond a questionnaire
      consisting of demographic data and educational background. They also answered 25
      multiple-choice questions about BLS, ACLS and medicolegal responsibilities of
      physicians in a face-to-face manner. The data were analyzed using Mann-Whitney U
      test and Kruskal-Wallis Analysis of Variance test. RESULTS: Mean level of
      knowledge was 45.4 on a hundred-point scale. Attendance to courses covering
      emergency aid and working as an ambulance physician for more than one year were
      associated with higher levels of knowledge (p=0.012; p=0.015). CONCLUSION: In
      service training should be undertaken to raise the level of knowledge of the
      physicians employed in rural EMS and to improve the quality of field care.

PMID- 16456753
TI  - Intrathoracic splenosis secondary to previous penetrating thoracoabdominal trauma
      diagnosed during delayed diaphragmatic hernia repair.
AB  - Although intraperitoneal splenosis is a very common disease, intrathoracic
      splenosis is very rare. It is generally an asymptomatic disease that occurs after
      thoracoabdominal trauma, and is diagnosed as an intrathoracic mass that leads to
      unnecessary investigations to be differentiated from other benign or malignant
      lesions of the chest. We present a patient with an intrathoracic mass which was
      preoperatively diagnosed as a diaphragmatic hernia on chest X-ray and magnetic
      resonance imaging. We have intraoperatively recognized that many pieces of
      splenic tissue have been herniated through a diaphragmatic defect, and formed
      intrathoracic splenosis. We repaired the diaphragmatic hernia defect after
      excision of fragments of the spleen.

PMID- 16456754
TI  - [Traumatic rupture of a pulmonary hydatid cyst: a case report].
AB  - We present a case of traumatic hydropneumothorax due to hydatid cyst rupture in a
      10 year-old girl. The patient was suspected to have a bronchial rupture because
      of prolonged massive air leak and she underwent cystotomy via right
      posterolateral thoracotomy. The patient was readmitted with dyspnea and chest X
      ray revealed a lung collapse 13 months postoperatively. Lung collapse was treated
      by using a Heimlich valve. Pulmonary hydatid cyst can be asymptomatic for a long
      time unless a complication occurs. Because of the high incidence of hydatid
      disease in our country, this condition should be considered in cases with
      hydropneumothorax. The use of a Heimlich valve may be a good choice in the
      management of persistent air leak and may reduce the need for surgery.

PMID- 16456755
TI  - [A case of rectus sheath hematoma].
AB  - Rectus sheath hematomas are uncommon and are being caused by the injuries of the
      epigastric vessels and the rectus muscle. They are usually located
      infraumblically and often misdiagnosed as inflammatory diseases or tumours of the
      abdomen. We present a 70-year-old woman who had complaints of severe abdominal
      pain on the left side, nausea and vomiting after heavy lifting. Rectus sheath
      hematoma was detected by abdominal ultrasonography and computerized tomography.
      The patient recovered uneventfully after bed rest, intravenous fluid replacement,
      blood transfusion and analgesic treatment. Computerized tomography must be chosen
      for definitive diagnosis. Ideal treatment is conservative.

PMID- 16456756
TI  - [Posttraumatic Chance fracture of the cervical spine in a case with ankylosing
      spondylitis: a case report].
AB  - Spinal fractures can occur after minor traumas due to the fragility of osseous or
      ligamentous structures of the spine in patients with ankylosing spondylitis. They
      are usually seen in the thoracolumbar region of the spine. However, the cervical
      region is an extremely rare location for these fractures. We present a 52-year
      old male with ankylosing spondilitis who had complaints of weakness in the lower
      extremities and difficulty with walking after a fall from height. Neurologic
      examination revealed a progressive loss of motor function. Magnetic resonance
      imaging showed a Chance fracture at the fifth and sixth cervical vertebrae. We
      performed a one-stage anterior cervical fusion and stabilization with posterior
      decompression. Postoperatively, there was a progressive neurologic improvement.
      However, the patient died due to pulmonary failure at the seventh day
      postoperatively.

PMID- 16456757
TI  - [Space-occupying lesion of the pancreas--how frequently not due to a suspected
      ductal adenocarcinoma?].
AB  - In patients with a space-occupying lesion of the pancreas at first a primary
      ductal adenocarcinoma is considered as the cause. Other tumours or metastases are
      assumed to occur very rarely. Therapy and prognosis of other pancreas tumours
      differ from therapy and prognosis of a primary ductal adenocarcinoma. We
      therefore examined the question of how frequently a space-occupying lesion of the
      pancreas was not due to a ductal adenocarcinoma in our case materials.
      Retrospectively 70 patients who had undergone a percutaneous puncture of a space
      occupying mass of the pancreas under ultrasonographic control were included in
      the study (34 women, 36 men). In 62 patients a clear histological diagnosis was
      possible on the basis of the biopsy. In 53 cases (76 %) a primary adenocarcinoma
      of the pancreas could be diagnosed. In 5 patients (7 %) these masses turned out
      to be metastases of a previously known malignant tumour disease (2 x mammary
      carcinoma, 2 x gastric carcinoma, 1 x sigmoid carcinoma). Other tumours could be
      detected in 4 cases (6 %) including a tuberculoma, an endocrine tumour, a
      fusocellular sarcoma with partial neurogenic differentiation and a large-cell and
      pleomorphic-cell anaplastic, partly sarcomatoid carcinoma. In patients with a
      space-occupying lesion of the pancreas, tumours other than a ductal
      adenocarcinoma are not rare. In particular, in cases of a previously known
      malignant tumour disease a space-occupying lesion of the pancreas can also turn
      out to be a metastasis. Every other individual tumour entity is rare. Other
      tumour entities at large, however, are found in daily routine. The preoperative
      biopsy of space-occupying lesions of the pancreas, therefore, still has a
      clinical importance for the further therapy planning.

PMID- 16456758
TI  - Urinary excretion of polyethylene glycol 3350 during colonoscopy preparation.
AB  - BACKGROUND: Whole gut lavage with a polyethylene glycol electrolyte solution
      (PEG) is a common bowel cleansing method for diagnostic and therapeutic colon
      interventions. Absorption of orally administered PEG from the gastrointestinal
      tract in healthy human beings is generally considered to be poor. In patients
      with inflammatory bowel disease (IBD), intestinal permeability and PEG absorption
      were previously reported to be higher than in normal subjects. In the current
      study, we investigated the absorption of PEG 3350 in patients undergoing routine
      gut lavage. METHODS AND RESULTS: Urine specimens were collected for 8 hours in 24
      patients undergoing bowel cleansing with PEG 3350 for colonoscopy. The urinary
      excretion of PEG 3350, measured by size exclusion chromatography, ranged between
      0.01 and 0.51 % of the ingested amount, corresponding to 5.8 and 896 mg in
      absolute amounts, respectively. Mean PEG excretion in patients with impaired
      mucosa such as inflammation or ulceration of the intestine (0.24 % +/- 0.19, n =
      11) was not significantly higher (p = 0.173) compared to that in subjects with
      macroscopically normal intestinal mucosa (0.13 % +/- 0.13, n = 13). CONCLUSION:
      The results indicate that intestinal absorption of PEG 3350 is higher than
      previously assumed and underlies a strong inter-individual variation.
      Inflammatory changes of the intestine do not necessarily lead to a significantly
      higher permeability of PEG.

PMID- 16456759
TI  - [Partial Budd-Chiari syndrome associated with a hypereosinophilic syndrome].
AB  - We report a rare case of hypereosinophilic syndrome associated with a partial
      obstruction of the hepatic veins (Budd-Chiari syndrome). The case was assessed by
      ultrasonic examination, computed tomography and magnetic resonance tomography. We
      postulate an association because endothelium damage and thrombosis is reported in
      hypereosinophilic syndromes. Elevated liver enzymes in a patient with
      hypereosinophilic syndrome could be associated with a Budd-Chiari syndrome.

PMID- 16456760
TI  - [Addison's disease as a rare cause of chronically elevated liver enzymes].
AB  - Common causes of chronically elevated serum liver enzymes include fatty liver
      disease, chronic viral hepatitis, autoimmune hepatitis, or hereditary metabolic
      disorders. Adrenocortical insufficiency can also cause elevated liver enzymes.
      Since 1990 only 11 cases have been reported. We here report a 52-year-old man
      with elevated liver enzymes (1.5 x upper limit of normal) over the past 10 years.
      Furthermore, hyponatremia and hyperkalemia were noted. He complained of fatigue
      and low blood pressure over the past few years. At physical examination a dark
      complexion was noted. After ruling out chronic viral hepatitis, autoimmune
      disease, metabolic or hereditary disorders, rare causes of elevated liver enzymes
      were considered. The endocrinological work-up revealed Addison's disease as cause
      of serum electrolyte disturbance and elevated liver enzymes. The patient was
      successfully treated with hydrocortisol and fludrocortisol. After one week, liver
      enzymes, serum electrolytes and arterial blood pressure had normalized. In
      conclusion, for patients with constantly elevated liver enzymes also rare,
      extrahepatic diseases have to be considered. Addison's disease is a rare but
      fully reversible cause for elevated liver enzymes.

PMID- 16456761
TI  - [Perspectives of cannabinoids in gastroenterology].
AB  - In early cultures, extracts of the plant Cannabis sativa were medically used for
      the treatment of gastrointestinal symptoms like nausea, vomiting, diarrhoea and
      abdominal pain. In the United States cannabis extracts were frequently used as
      drugs, e. g., for the treatment of diarrhoea, until around 1920. The possibility
      of cannabis abuse resulted in a worldwide prohibition and thus the temporary
      ending of the medical use of cannabinoids. The characterisation of an endogenous
      cannabinoid system consisting of receptors, endogenous agonists, antagonists and
      degrading enzymes opens the door for a comeback of cannabinoids in medicine. The
      clinically proven effects in the treatment of pain, cachexia in conjunction with
      HIV, or malignant disease and treatment of nausea and vomiting in conjunction
      with chemotherapy now result in the prescription of cannabinoids as valuable
      medication. This review will discuss the value of cannabinoids in the treatment
      of nausea and vomiting, i. e., the indications for which cannabinoids are
      presently used in gastroenterology. Additionally, this review will discuss
      potential indications within gastroenterology, where results from basic research
      or individual observations suggest that a future use of cannabinoids in
      gastroenterology seems possible.

PMID- 16456762
TI  - [Antibiotic-associated diarrhea].
AB  - The incidence of antibiotic-associated diarrhea (AAD) differs with the antibiotic
      and varies from 15 - 25 %. Most cases of AAD are directly or indirectly caused by
      alterations of gut microflora by the antibiotics resulting in clinically mild AAD
      cases due to functional disturbances of intestinal carbohydrate or bile acid
      metabolism. Alternatively, changes in the gut flora allow pathogens to
      proliferate. Clostridium difficile is responsible for 10 - 15 % of all cases of
      AAD and almost of all cases of antibiotic-associated pseudomembraneous colitis.
      There is also a growing body of evidence which supports the responsibility of
      Klebsiella oxytoca for the development of antibiotic-associated hemorrhagic
      colitis. Diagnosing Clostridium difficile-associated diarrhea should be based
      both on fecal-cytotoxin detection and culture. With respect to specific therapy,
      metronidazol has become the first choice whereas treatment with oral vancomycin
      should be reserved for patients who have contraindications or intolerance to or
      who have failed to respond to metronidazole. Probiotics such as Sacharomyces
      boulardii can reduce the risk of development. Restrictive antibiotic policies (e.
      g. restricting clindamycin and cephalosporins) and the implementation of a
      comprehensive hospital infection control have also been shown to be effective in
      reducing the incidence of AAD.

PMID- 16456763
TI  - [Molecular therapy for HCC?].

PMID- 16456764
TI  - [Branched chain amino acids as oral supplements in liver cirrhosis].

PMID- 16456765
TI  - Gunshot wounds involving the brachial plexus: surgical techniques and outcomes.
AB  - This paper presents the management and outcomes for two consecutive operative
      series of gunshot wounds (GSWs) involving the brachial plexus. The cases were
      from Louisiana State University Health Sciences Center (LSUHSC) and were obtained
      by retrospective chart reviews. Series 1 includes patients with injuries managed
      between 1968 and 1980 and series 2, from 1981 to 1998. Pre- and postoperative
      motor function was assessed using the LSUHSC grading system. The outcomes for
      each surgical technique for each series are presented. Fewer cases of brachial
      plexus elements injured by GSWs in series 2 may be due to decreased firearm
      related injuries between 1993-1997, i.e., 39,595 versus 32,436 deaths,
      respectively. The graft repair increase in series 2 may have been the result of
      more severe injuries, since documented trends between 1971 and 1997 show the use
      of larger caliber bullets. This paper shows that with the outlined management and
      surgical techniques, surgery on certain GSWs of the brachial plexus is
      worthwhile.

PMID- 16456766
TI  - Radial sensory neurotization of the thumb and index finger for prehension after
      proximal median and ulnar nerve injuries.
AB  - Proximal median nerve injuries are functionally disabling, secondary to both
      motor and sensory deficits. Reestablishment of sensation relies on slow axonal
      regeneration originating from the site of injury after either primary nerve
      repair or the use of autogenous nerve grafts. This regeneration can take 2 or
      more years to restore sensation to the hand, depending on injury location. Distal
      sensory nerve transfers shorten the recovery time by decreasing the required
      regeneration distance. The authors present two case reports of patients with
      proximal median nerve injury, who underwent radial sensory nerve transfers to the
      ulnar digital nerve of the thumb and the radial digital nerve of the index
      finger. Protective sensation returned to the index and thumb fingertips at 3
      months. By 6 months, both patients attained sufficient sensation to permit active
      lateral key pinch. At 9 months, each patient had moving sensation; and by 14
      months, each patient attained proper localization. Successful digital nerve
      transfers of the dorsal radial sensory nerves in patients with high proximal
      median nerve injuries return sensation faster than traditional median nerve
      repairs. Use of this technique will significantly reduce the insensate time in
      patients with this unfortunate injury.

PMID- 16456767
TI  - Two cases of big-toe replantation: a ten-year follow-up.
AB  - It is rare for traumatic amputation of the big toe to occur as a single injury.
      This trauma is especially significant in children for influencing foot
      development and for possible psychological impact. Two cases of successful
      replantation of completely amputated big toes in two girls, 2 years 7 months and
      5 years 2 months old, are presented. Follow-up was 10 years. In the younger
      child, the replanted big toe was 49.2 percent shorter compared to the
      contralateral side, because growth was limited by the affected growth zone in the
      proximal phalanx. In the older child, the growth zone of the bone was intact,
      with consequent bone growth unimpaired, and an initial shortage of 10.4 percent
      was reduced to 2 percent compared to the contralateral side.

PMID- 16456768
TI  - Microdialysis detects postoperative perfusion failure in microvascular flaps.
AB  - In microvascular tissue transfers, it is essential postoperatively to follow-up
      on the perfusion of the transferred flap because of the risk of anastomotic
      failure. The diagnosis of pedicle obstruction is usually made by clinical
      observation, but some techniques have been reported as more reliable than
      clinical observation in detecting perfusion failure. The authors used
      microdialysis (MD), a method developed to assess in situ tissue metabolism, in
      the follow-up of 80 consecutive microvascular flaps from October, 2001 to
      October, 2003. Of the 78 flaps with postoperative data, 58 flaps were uneventful
      clinically and using MD, and served as the reference material for normal
      postoperative metabolism. Twenty flaps showed some abnormality in the clinical
      course or with MD. Of these, 13 flaps were reoperated for anastomosis thrombosis
      (9 arterial, 4 venous). All thromboses were clearly recognized by MD via a
      decrease in the glucose concentration in the tissue (< 2.7 mmol/l) and an
      increase in the lactate concentrations (> 5.7 mmol/l). In some cases, MD
      indicated a pathological trend in glucose and lactate concentrations hours before
      there were any clinical signs. A system of alarm levels was developed for the
      staff: when the limits were reached, a critical evaluation of the situation was
      undertaken, and the need for reoperation was considered. In the series, the
      salvage rate of all thrombosed flaps was 77 percent, with a final success rate in
      microvascular reconstruction of 95 percent. No flap was lost due to a delay in
      the diagnosis of secondary ischemia, if on-line MD monitoring was available.
      Microdialysis is a clinically feasible and sensitive monitoring method for all
      kinds of microvascular flaps, especially for those in which clinical observation
      is difficult or impossible. The performance of the analysis is easy and can be
      done by even less experienced nursing staff working in institutes with a low
      frequency of microsurgery.

PMID- 16456769
TI  - Free anterolateral thigh flap for reconstruction of major craniofacial defects.
AB  - Free-tissue transfer has revolutionized skull-base surgery by expanding the
      ability to perform cranial base resection and by improving the quality of
      reconstruction. The anterolateral thigh flap has come recently into use in the
      field of head and neck reconstruction. Its role in craniofacial and midface
      reconstruction has not been specifically defined. This study involved a total of
      18 patients who were treated over a 5-year period from 1998 to 2003. Seventeen
      patients had locally advanced head and neck cancer, requiring craniofacial
      resection, and one patient had a complicated gun shot wound of the forehead.
      Thirteen patients were treated at the National Cancer Institute, Cairo
      University, Egypt, and five patients at the University of Miami, Florida. The
      patients presented with defects of the anterior skull base (5), lateral skull
      base (3), scalp and calvarium (3), and the midface (7). The anterolateral thigh
      flap was used as a myocutaneous flap in 11 cases and as a perforator
      fasciocutaneous flap in seven cases. Musculocutaneous perforators supplied the
      majority of flaps (17/18). Total flap survival occurred in 17 cases; one patient
      developed complete flap necrosis. The most commonly used recipient vessels were
      the facial vessels and the external jugular vein. Major complications included
      one case with meningitis; the patient died after failure of treatment. Another
      patient died 6 weeks postoperatively from pulmonary embolism. One patient
      developed CSF leak that stopped spontaneously. In addition, two patients
      developed minor wound dehiscence that healed spontaneously. The donor-site wound
      healed without problems except in two cases. One patient had an incomplete take
      of the skin graft; the other developed wound infection and superficial sloughing.
      Both wounds healed spontaneously. In addition to the feasibility of simultaneous
      flap harvesting with tumor resection, the flap's advantage in skull base
      reconstruction is its reliable blood supply, which can provide adequate dural
      cover and protection of the brain. Its size and moderate thickness are suitable
      for reconstruction of scalp and calvarial defects. The abundance of reliably
      vascularized fat in the flap may be an advantage in long-term maintenance of the
      volume of the flap in midface reconstruction. Similar to other soft tissue flaps,
      additional skeletal reconstruction may still be required to achieve an optimal
      functional and aesthetic result.

PMID- 16456770
TI  - A simplified design of a dual island fasciocutaneous free flap for simultaneous
      pharyngoesophageal and anterior neck reconstruction.
AB  - Reconstruction of the pharyngoesophagus and pharynx can be especially challenging
      in patients with prior irradiation, recurrent disease, and compromised or
      deficient anterior neck skin. The authors report their experience with seven
      patients who underwent pharyngoesophageal reconstruction with a new flap design
      that addresses both the concerns of monitoring the internal skin tube and
      replacing the external neck skin with one flap. This design has two skin islands,
      one that is tubed and the other left flat. The authors call this design "the
      paddle flap" because together its two components resemble a paddle. The tubed
      portion resembles the "handle" of a paddle that is used for esophageal
      reconstruction, and the cutaneous paddle is then folded over the "handle" to
      provide external skin. The external skin portion of the flap not only provides an
      external monitoring segment but releases tension on the neck apron incision and
      may replace compromised native neck skin. The length of esophageal defects ranged
      from 4 to 11 cm and the anterior cervical skin requirements ranged from 4 x 2 cm
      to 10 x 12 cm. Follow-up has been between 18 months and 4 years. There were no
      partial or complete flap losses. All patients are currently tolerating an oral
      diet. There was one case of partial donor-site skin graft loss which was treated
      with re-grafting. There were two cases of stricture formation which were treated
      successfully with neo-esophageal dilatation. This new simple, versatile design of
      a cutaneous free flap addresses both concerns of monitoring the internal skin
      tube and dealing with compromised overlying skin in patients undergoing
      pharyngoesophageal reconstruction. The paddle flap design can be utilized with
      any thin cutaneous free flap and may offer an advantage when an external monitor
      is desired and anterior neck skin requires supplementation or replacement.

PMID- 16456771
TI  - Decompression of the lateral femoral cutaneous nerve in the treatment of meralgia
      paresthetica.
AB  - Meralgia paresthetica (MP) is a painful mononeuropathy of the lateral femoral
      cutaneous nerve (LFCN). Neurolysis is reserved for patients with MP who respond
      poorly to medical management. This study retrospectively evaluated the outcomes
      of 41 patients who underwent either unilateral or bilateral neurolysis of the
      LFCN for a total of 48 procedures. Twenty-nine procedures involved neurolysis of
      the LFCN alone and 19 procedures involved neurolysis of the LFCN and resection of
      one or more additional nerves (ilioinguinal, iliohypogastric, genitofemoral).
      Overall, surgical outcome was considered by patients to be successful in 77
      percent of cases. LFCN neurolysis alone had better results, compared to combined
      LFCN neurolysis and nerve resection. The conclusion is that neurolysis of the
      LFCN is an effective treatment for MP in properly selected patients.

PMID- 16456772
TI  - Fibrin glue: an alternative technique for nerve coaptation--Part I. Wave
      amplitude, conduction velocity, and plantar-length factors.
AB  - The search for better surgical repair of nerve injuries should be aimed at
      uncovering alternatives that not only are efficient, but also enhance nerve
      growth. The purpose of this study was to compare functional nerve responses
      following repair with either a traditional microsuture technique or Quixil human
      fibrin sealant. Thirty female Lewis rats received transection of the right
      sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n =
      15) or Quixil fibrin glue (n = 15). Functional results were assessed at 2, 6, and
      12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve
      recordings were also performed 12 weeks postoperatively. Rats receiving Quixil
      nerve repair returned to baseline performance on the walking-track analysis
      significantly faster than those with microsuture repairs (6 and 12 weeks
      postoperatively; p < 0.0001). Recovery of nerve conduction velocities and wave
      amplitudes was also significantly better in the nerves repaired with Quixil than
      in those repaired with microsuture (p's < 0.0001). Quixil human fibrin sealant is
      a good alternative to traditional microsuture nerve repair techniques.

PMID- 16456773
TI  - Fibrin glue: an alternative technique for nerve coaptation--Part II. Nerve
      regeneration and histomorphometric assessment.
AB  - The results of nerve repair with fibrin glue and microsuture were evaluated in
      rat nerve transection models. Ninety Wistar-Furth rat median nerves were exposed,
      transected, and repaired in an end-to-end fashion with one of four
      substances/techniques: 1) human fibrin sealant (Quixil); 2) autologous graft and
      human fibrin sealant (Quixil); 3) bovine fibrin sealant (Tissucol); and 4) nylon
      microsuture, epineurial technique. Histologic analyses were performed at 3-, 6-,
      and 9-month postoperative intervals, and factors evaluated included: presence of
      inflammatory cells (i.e., macrophages and T cells); number of Schwann cells at
      the repair site; number of blood vessels; fibrosis; axonal regeneration; and
      fiber alignment. An additional group underwent histologic analysis at 3 weeks
      following repair with Quixil. Surgical time of repair was also measured. Nerve
      repairs performed with fibrin sealants produced less inflammatory response and
      fibrosis, and better axonal regeneration and fiber alignment than nerve repairs
      performed with microsuture. In addition, the fibrin sealant techniques were
      quicker and easier to use. The authors conclude that fibrin sealant represents a
      good alternative technique to microsuture for peripheral-nerve repair.

PMID- 16456774
TI  - Intramuscular administration of vascular endothelial growth factor augmenting
      collateral circulation in a rat hindlimb replantation model.
AB  - This study evaluated the effect of exogenous vascular endothelial growth factor
      (VEGF) on augmentation of collateral circulation in a rat hindlimb replantation
      model. Twenty-eight rats, divided into four groups, underwent right hindlimb
      replantation. In experimental Group 1, the rats received daily intramuscular VEGF
      injections (1 microg/kg). In Group 2, the rats received 25 microg/kg VEGF
      injections. In Group 3, the rats received 50 microg/kg VEGF injections. In Group
      4, the control group, rats received saline injections. Seven days after
      replantation, the repaired femoral vessels were excised. Seven days after
      excision of the femoral vessels, toe necrosis ratios of the replanted hindlimbs
      were grossly examined, and calf blood pressures were measured. Angiography was
      performed and muscle tissue was biopsied for histology. The results showed that
      administration of VEGF significantly decreased toe necrosis and improved calf
      blood pressure ratio, angiographic score, and capillary density in the replanted
      hindlimbs that underwent late vessel excision. The effect of VEGF was
      significantly dose-dependent. The authors conclude that VEGF can augment
      angiogenesis and collateral vessel formation in replanted limbs, and improve
      survival in replanted limbs with potential late arterial insufficiency.

PMID- 16456775
TI  - An analysis on transcriptional regulation activity of human XBP1 gene 5' upstream
      DNA sequences.
AB  - OBJECTIVE: To analyze the transcription activation and possible regulation
      mechanism of human X-box binding protein 1(XBP1)gene 5'upstream DNA sequence in
      different cell lines. METHODS: Six kinds of XBP1 promoter deletion mutants were
      cloned into pGEM-Teasy vector, which included XBP1 gene 5' upstream -1039 to 66
      bp,-859 to 66 bp,-623 to 66 bp,-351 to 66 bp,-227 to 66 bp,-227 to -45 bp
      respectively. Every deletion mutant sequence was cut from Teasy-XBP1p by KpnI and
      Xho I, and subcloned into pCAT3-Basic to produce a set of constructs termed as p1
      XBP1p, p2-XBP1p, p3-XBP1p, p4-XBP1p, p5-XBP1p, p6-XBP1p, respectively. The
      transcription activity of each construct was detected after transiently
      transfecting K562, HepG2,NIH-3T3 and L0(2)cell with FuGENE 6 transfection
      reagent. Cells transfected by pCAT3-Basic or pCAT3-Promoter were used as negative
      and positive controls. The activity of chloramphenicol acetyltransferase(CAT),
      which reflects the transcription activation of the XBP1 gene promoter, was
      detected by ELISA after 48 hours of transfection. RESULTS: The reporter vectors
      of six kinds of XBP1 promoter deletion mutants were successfully constructed, as
      confirmed by restriction enzyme digestion and sequencing. The activities of p4
      XBP1p and p5-XBP1p were higher than the other deletion mutants in K562 and HepG2.
      And the activity of p5-XBP1p was the highest in HepG2. There was no activity
      detected from any transfected NIH-3T3. CONCLUSION: The XBP1 gene promoter can
      transactivate its downstream gene to transcription. The core sequence of XBP1
      promoter was implied between -227 bp and 66 bp. This sequence was connected with
      the transcriptional activity of XBP1 promoter closely. Its transcription activity
      varies with different cell lines. XBP1 promoter might drive gene expression with
      cell-type specificity.

PMID- 16456776
TI  - Average-12.9 chromosome imbalances coupling with 15 differential expression genes
      possibly involved in the carcinogenesis, progression and metastasis of
      supraglottic laryngeal squamous cell cancer.
AB  - OBJECTIVE: With the objective of discovering novel putative chromosomal regions
      and special genes involved in the carcinogenesis, progression and metastasis of
      laryngeal squamous cell cancer (LSCC). METHODS: DNA copy profile of LSCC were
      obtained and analyzed by comparative genomic hybridization (CGH) and a
      computerized digital image analysis system. cDNA microarray of LSCC was performed
      and the profile was analyzed by Hierarchical clustering. RESULTS: CGH analysis
      showed average-12.9 gains and losses of chromosomes in LSCC. Relatively high
      frequencies of gains were found at 3q15-21 (14/18), 5p12-13 (11/18), 8q22-24
      (6/18), 11q12-13 (8/18), 15q21-23 (7/18) and 18p11 (8/18), while those of losses
      at 1p13-21 (8/18), 3p21-23 (14/18), 5q21-22 (14/18), 9p12-pter (11/18) and 13q21
      31 (8/18). Hierarchical clustering analysis showed that the differentially
      expressed genes were segregated into three groups. Three genes differentially
      expressed in process I (normal tissue to cancer) and process II (cancer to lymph
      node metastasis), and the Cy5/Cy3 ratios of twelve genes were either higher than
      5.0 or lower than 0.2 in process I or process II. The fifteen special genes were
      first reported possibly to be the relationships with LSCC. In particular, 4 genes
      of them, which were cytochrome C oxidase Va, PPBP, EPHX2 and PON1, were first
      reported to correlate with tumorigenesis. SH3GL2, which was one of the 15 special
      genes, was located at one of the special chromosome regions, 9p12-pter.
      CONCLUSION: The important genes and special chromosomal aberrances might provide
      us a clue for further investigation of carcinogenesis, progression and metastasis
      in LSCC.

PMID- 16456777
TI  - The molecular cytogenetic aberration analyzed by comparative genomic
      hybridization and its significance in diffuse large B-cell lymphoma.
AB  - OBJECTIVE: To identify genetic alterations in diffuse large B-cell lymphoma
      (DLBCL) and to analyse the relationship between the genetic aberrations and the
      clinical characteristics. METHODS: Using comparative genomic hybridization (CGH)
      to investigate the genomic changes in 24 cases of DLBCL and to analyse the
      relationship between these aberrations and clinical parameters including Ann
      arbor stage, systemic symptoms, chemotherapy efficacy and survival. RESULTS:
      Aberrations were detected in 62.5% patients of 24 cases; the most common
      chromosomal alterations included loss of 6q15-21 as well as gain of 18q11-ter, of
      which the incidences were 20.8% and 16.7%, respectively; with comparing clinical
      parameters between patients with normal CGH and abnormal CGH, we found that
      patients with abnormal CGH suffered more from stage III-IV and had higher
      incidence of systemic symptoms, poor chemotherapy efficacy and poor survival
      (P<0.05), but there was no difference observed in the incidence of extranodal
      involvement between two groups. CONCLUSION: The gains and/or losses of genomic
      DNA from DLBCL patients are the common molecular cytogenetic aberrations; loss of
      6q15-21 and gain of 18q11-ter are nonrandom event to DLBCL patients; abnormal CGH
      is a clinical parameter reflecting malignant progressive course and poor survival
      to DLBCL patients.

PMID- 16456778
TI  - A novel microsatellite within intron 8 in caspase10 gene in Chinese of Han
      nationality.
AB  - OBJECTIVE: To investigate polymorphisms in the coding exons and their splicing
      areas of caspase10 gene (CASP10) in Chinese of Han nationality. METHODS:
      Polymerase chain reaction (PCR), denaturing high-performance liquid
      chromatography (DHPLC), direct sequencing and clonal sequencing were used to
      analyze the exon 9 and its flanking sequences. RESULTS: In 70 blood samples of
      Chinese subjects researched the known single nucleotide polymorphisms (SNPs) in
      the exon 9 of CASP10 gene published in dbSNP of NCBI were not identified. We
      found a short sequence with more than ten continuous and repeated T nucleotides
      within the intron 8 near the exon 9 and the length of repeated sequence
      nucleotides T was different in samples. Clonal sequencing analysis indicated that
      it was a microsatellite of single nucleotide-repeated sequence. The recurrence
      and specificity of same result was further confirmed by PCR with high fidelity
      polymerase and sequencing. Furthermore all of 70 blood samples detected by DHPLC
      showed heterozygous profiles. We named it as IVS8-13(T)n temperately. CONCLUSION:
      Our research suggested that the site be a microsatellite of single nucleotide
      repeated sequence. Meanwhile, our data further showed that it was quite different
      from that by querying SNP database of non-Chinese population in NCBI, in the same
      region a SNP of type of insertion deletion existed. It could be inferred that the
      difference between the populations might be associated with the genetic
      characteristics of ethnics. The significance of the microsatellite in CASP10 gene
      in Chinese of Han nationality remains to be elucidated.

PMID- 16456779
TI  - [The wild-type alpha-synuclein over-expression to induce the protein aberrant
      aggregation of alpha-synuclein in HEK293 cells in vitro].
AB  - OBJECTIVE: To investigate over-expression of wild-type alpha-synuclein inducing
      the aberrant aggregation of alpha-synuclein in HEK293 cell in vitro. METHODS: The
      cDNA encoding the human alpha-synuclein without the stop code was cloned into
      PGEM T-easy vector. Using enzyme map and DNA sequencing analyzed and determined
      the recombinant plasmid, and then sub-clone the alpha-synuclein cDNA fragment
      into pEGFP-N1 vector. The recombinant plasmids alpha-synuclein-pEGFP were
      transfected into HEK293 cells by lipofectamin 2000. The aberrant aggregation of
      alpha-synuclein was measured by EGFP fluorescence, anti-alpha-synuclein
      immunocytochemistry. The inclusions in the cultured cells were identified with HE
      staining. RESULTS: The restriction enzyme map suggested that eukaryotic
      expression vector for human wild-type alpha-synuclein gene was constructed
      successfully. By EGFP fluorescence, anti-alpha-synuclein immunocytochemistry, it
      could be observed that the alpha-synuclein protein could aggregate in cytoplasm
      and the Lewy body-like inclusions found in cytoplasm of cultured cells.
      CONCLUSION: The over-expression of wild-type alpha-synuclein can induce protein
      aberrant aggregation and Lewy body-like inclusions formation in cytoplasm of
      HEK293 cell in vitro.

PMID- 16456780
TI  - [An analysis for the phenotype and genotype of autosomal dominant polycystic
      kidney disease from two Chinese families].
AB  - OBJECTIVE: To scan for mutations of polycystic kidney disease 1 gene (PKD1) in
      Chinese population in order to find some features about Chinese patients and a
      better approach to detect mutations. METHODS: Twenty-five PKD-affected
      individuals from twenty-one unrelated genealogies and sixteen controls
      participated in the study. Thirty-five blood samples and six tissues were
      obtained after receiving informed consent and were in accordance with
      institutional ethical guidelines. Genomic DNA was isolated from peripheral blood
      using standard procedures. PCR amplification of genomic DNA was performed to
      generate the aimed fragments. Amplified fragments were analyzed by denaturing
      gradient gel electrophoresis (DGGE). A GC clamp was attached to the 5' primer.
      After that, the abnormal fragments were sequenced on freshly amplified specific
      PCR products with the dideoxynucleotide chain termination method. Sequencing was
      performed for all samples to evaluate DGGE. RESULTS: Aimed fragments of exons 44
      and 45 were amplified. DGGE detected eleven abnormal PCR fragments. Two novel
      mutations were identified by sequencing, included one nonsense mutation (C12217T)
      and one frameshift (12431delCT). In addition, one polymorphism (A50747C) was
      identified. The mutation detection rate is 8% in our study. CONCLUSION: Two novel
      pathogenic mutations were detected, including one nonsense mutation (C12217T) and
      one frameshift (12431delCT).

PMID- 16456781
TI  - [BRCA1 and BRCA2 gene mutations of familial breast cancer from Shanghai in
      China].
AB  - OBJECTIVE: To investigate the prevalence of BRCA1 and BRCA2 gene mutations among
      breast cancer patients with affected relatives in Shanghai of China. METHODS:
      Thirty-five breast cancer patients who had at least one first-degree relative
      affected were analyzed, among whom 13 patients suffered from breast cancer at age
      of less than 40 years. A comprehensive BRCA1 and BRCA2 mutation analysis was
      performed through denaturing high-performance liquid chromatography (DHPLC) and
      subsequent DNA direct sequencing. RESULTS: Four mutations in BRCA1 gene,
      including 2 novel splice-site mutations (IVS17-1G>T, IVS21+1G>C) and 2 frameshift
      mutations (1100delAT; 5640delA) were identified. One frameshift mutation
      (5802delAATT) was detected in exon 11 of BRCA2. Additional 12 novel single
      nucleotide polymorphisms(SNPs) were detected, including a novel unclassified
      variant and 7 novel intronic variants in BRCA1, and 4 novel intronic variants in
      BRCA2, with which all caused no alteration of amino acid coding. The mutation
      frequency of BRCA1 and BRCA2 in patients with family history was 11.4% and 2.9%,
      respectively. CONCLUSION: Two novel mutations in BRCA1 may be mutations
      characterized to familial breast cancer of Chinese Shanghai population. The BRCA2
      may contribute to mutation less than BRCA1 in familial breast cancer. Our data
      contribute to information on mutation spectrum of BRCA gene in Chinese population
      and also offer a recommended screening mode for clinical genetic testing policy
      in China.

PMID- 16456782
TI  - [The analysis for mRNA mutation of MLH1, MSH2 genes and the gene diagnosis for
      hereditary nonpolyposis colorectal cancer].
AB  - OBJECTIVE: To identify hereditary nonpolyposis colorectal cancer (HNPCC) families
      based on the germline mutations of MLH1 and MSH2 mRNA. METHODS: RNA was extracted
      from the peripheral blood of the 14 members from 12 different families fulfilling
      Amsterdam Criteria II. The germline mutations of MLH1 and MSH2 mRNA were detected
      by cDNA sequencing analysis following reverse transcription-PCR(RT-PCR) with
      special primers, heat-resistance reverse transcriptase, and expand long template
      PCR. DNA was extracted from the peripheral blood of the 14 members, the
      corresponding exons, in which mutations were found using the above method, were
      amplified with Taq enzyme, sequencing analysis was followed. RESULTS: Six
      germline mutations were detected and identified from the 6 different families
      based on mRNA, 4 of them to be in MLH1, the other 2 in MSH2. The MLH1 mutations
      distribute in the exon 8, 12, 16, and 19. The MSH2 mutations distribute in exons
      1 and 2. The 6 mutations were identified from the corresponding exons
      respectively in genomic DNA sequencing analysis. The mutation types involve in 4
      missense, 1 silent, and 1 non-coding area mutations. Five out of the 6 mutations
      have not been reported previously. Five out of the 6 mutations were pathological,
      involving in 5 different families. The five families were identified to HNPCC
      families. CONCLUSION: HNPCC family can be identified with RNA-based sequencing of
      MLH1 and MSH2 from peripheral blood, which has the advantages of both cost, time
      saving and high sensitivity.

PMID- 16456783
TI  - [The down regulation of VEGF gene expression may link to change the expression
      profile of genes in leukemia cell line K562].
AB  - OBJECTIVE: To explore the potential effects of anti-VEGF hairpin ribozyme gene to
      gene expression profiles in leukemia cell line K562. METHODS: The lipofectamine
      mediation was used to transfect the recombinant eukaryotic expression plasmid
      (pcDNA3-RZ) containing anti-VEGF hairpin ribozyme gene and the non-recombinant
      vector as control into K562 cells. And the positive clones were screened by G418.
      Ribozyme gene in K562 cells was confirmed by PCR. Fluorescent real time reverse
      transcription-PCR(RT-PCR) and Western blotting were employed to detect the
      expression of VEGF mRNA and protein in leukemia cells. cDNA microarray was used
      to explore the alteration of gene expression profiles when decreasing VEGF gene
      expression in leukemia cells. Expression of PCNA and GSN genes were verified by
      semi-quantitative RT-PCR. RESULTS: The pcDNA3-RZ and pcDNA3 had been transfected
      into the human leukemia cell line K562 and positive clones been screened by G418.
      Stable expression of the ribozyme gene in K562 cells was confirmed by PCR. The
      level of VEGF mRNA and protein decreased dramatically in K562-RZ cells when
      compared with K562 or K562-PC (K562 cell transfected with empty vector) cells.
      The gene expression profiles were changed by transfection of anti-VEGF hairpin
      ribozyme gene into K562 cells. Among 4096 gene clones on the microarray, 191
      (4.86%) genes were detected to have the marked changes with 104 down-regulated
      and 87 up-regulated, that were functionally related to cell cycle progression,
      gene replication, metabolism, cell apoptosis, cell signal transduction, and
      oncogenes etc. An increased expression of GSN gene and a decreased expression of
      PCNA gene in K562/RZ cells have been detected by RT-PCR. CONCLUSION: Down
      regulation of VEGF gene by introducing anti-VEGF hairpin ribozyme gene can alter
      the gene expression profiles in K562 cells, leading to change of cell growth,
      differentiation and apoptosis in K562/RZ cells.

PMID- 16456784
TI  - [Constructions of Gcn5 shRNAs interfere the histone acetylation modification with
      stem cell differentiation].
AB  - OBJECTIVE: To construct the Gcn5 shRNA plasmids and to explore the Gcn5 shRNA
      role in histone acetylation modification with the differentiation of stem cells.
      METHODS: Seven shRNA fragments were recombined into pGenesil-1 vector to form 7.
      Gcn5 shRNA constructions. The mesenchymal stem cells (MSCs) induced for two weeks
      with 5-aza were transfected by the plasmids with lipofectamine2000. Polyclonal
      antibodies labeled with TRITC were used to identify the acetylation in MSCs with
      or without Gcn5 shRNA constructions. The efficiencies of transfection and RNAi
      were calculated based on the ratio of GFP (green fluorescence)/DAPI (blue
      fluorescence) and TRITC (red fluorescence)/DAPI, respectively. RESULTS: Seven
      Gcn5 shRNA plasmids or constructions were identified by restriction endonucleases
      Pst I/Sal I and DNA sequencing. Acetylation block was observed after Gcn5 shRNA
      plasmids transfected into cells. Fluorescent intensity of TRITC in nucleuses were
      decreased remarkably, or even disappeared in MSCs. The efficiencies of
      transfection and RNAi were 93.7% and 46.6%, respectively. CONCLUSION: The Gcn5
      shRNA plasmids constructed in the present study can decrease the histone
      acetylation during cell differentiation. It sets the basis for further exploring
      the role of acetylation in the regulation of cell differentiation.

PMID- 16456785
TI  - [Sequence analysis of a novel HLA-DRB1 allele, DRB1 * 1212].
AB  - OBJECTIVE: To investigate the molecular genetics basis for HLA novel allele HLA
      DRB1*1212 in Chinese population. METHODS: Genomic DNA was extracted from whole
      blood by salting-out method. HLA-DRB1 gene exon 2 was amplified by PCR with group
      specific primers from genomic DNA. PCR products were cut back from agarose gels
      and purified to sequence directly. The polymerase chain reaction-sequence
      specific oligonucleotide probes (PCR-SSO) was performed to confirm the mutations
      which were detected by sequencing in this study. RESULTS: The sequencing results
      showed HLA-DRB1 alleles of the proband as DRB1*090102 and the novel allele. The
      sequences of the novel allele have been submitted to GenBank (AY899825). Through
      BLAST analysis, the novel allele was found to be different from DRB1*120101 at
      position 199A-->C in exon 2, that results in an amino acid change from Ile to Leu
      at codon 67. CONCLUSION: This allele is a novel and has been officially named as
      DRB1*1212 by the WHO Nomenclature Committee.

PMID- 16456786
TI  - [HLA-B gene polymorphism detected by high-resolution sequence-based typing in
      Guangdong Han populations].
AB  - OBJECTIVE: To investigate the genetic polymorphism of HLA-B locus in Guangdong
      Han population and compare the characteristic of the allele frequency
      distribution with that in other populations. METHODS: A total of 562 cord blood
      samples from Guangzhou Cord Blood Bank were analyzed by sequence-based typing.
      Then the sequences encompassing exons 2, 3, and 4 for HLA-B gene were analyzed by
      direct sequencing of PCR products. The allele frequency distribution of HLA-B in
      this population was compared with that in other populations. RESULTS: A total of
      59 different HLA-B alleles were detected, and among them were 6 HLA-B alleles
      with frequencies higher than 5%: HLA-B*4601 (14.5%), HLA-B*400101 (14.4%), HLA
      B*1502 (11.5%), HLA-B*1301 (8.6%), HLA-B*5801 (8.1%) and HLA-B*380201 (6.4%); the
      total frequency of these six alleles was 63.5%. At the same time, there were 30
      kinds of HLA-B allele with frequencies lower than 0.5%; the total frequency of
      these alleles was 4.9%. Maximum variation at HLA-B was seen in the HLA-B*15
      allele family (nine alleles). Comparison of the HLA-B frequencies in different
      populations showed a close relationship of Guandong Han population with the
      Chinese populations from Hong Kong and Singapore, respectively. CONCLUSION: The
      results have shown the characteristic of HLA-B distribution and provided more
      accurate genotypic data that may serve as normal reference value for the Han
      population in Guangdong, China.

PMID- 16456787
TI  - [Polymorphisms of neural nicotinic cholinergic receptor alpha 4 gene of Chinese].
AB  - OBJECTIVE: To screen for polymorphisms in alpha 4 subunit (principal subunit of
      nAChR) gene (CHRNA4). METHODS: DNA was extracted from leukocytes of all subjects
      including 100 healthy senior people and 100 patients with Parkinson's disease
      (PD). The exons and adjacent intron regions of CHRNA4 were amplified with PCR.
      SNPs were screened by denatured high performance liquid chromatography (DHPLC)
      techniques and restriction fragment length polymorphisms. Potential mutations
      were confirmed by sequencing. RESULTS: Total 10 polymorphisms were detected and
      identified in coding and adjacent intron regions of nAChR alpha 4 gene, that are
      420C/T (0.873/0.127), 870C/T (0.828/0.172), 1440A/C (0.858/0.142), 1860C/T
      (0.738/0.262), 1890C/T (0.605/0.395), intron 5 +14T/C (0.553/0.447), intron 2
      +22G/A (0.873/0.127), intron 3 +182 Del22bp (0.813/0.187), 1758C/T and 1809C/T
      (reference for coding sequence is GenBank SNPs 000744), of which the last three
      are novel mutations. PD patients appeared higher frequency of deletion in intron
      3+182(0.235) than normal controls (0.140)(P=0.015). CONCLUSION: nAChR alpha 4
      gene is polymorphic. PD patients take higher frequency of intron3+182 Del 22 bp.

PMID- 16456789
TI  - [The regulating roles of angiopoietins/TEK-2 in angiogenesis].
AB  - Angiopoietins(ANGPT) and their endothelial cell-specific tyrosine kinase
      receptors TEK are the major regulators of blood vessels angiogenesis under
      physiological and pathologic conditions. ANGPT1 is essentially involved in
      maturation, stabilization, and remodeling of blood vessels through inducing TEK
      autophosphorylation, promoting endothelial cell migration and survival. Instead,
      ANGPT2 appears to act as a natural antagonist of ANGPT1, it can activate vascular
      remodeling with the presence of vascular endothelial growth factor(VEGF) or
      regress frank blood vessels under the absence of VEGF. High expression of
      angiopoietins and TEK is often detected in tumor tissues. Many studies showed
      that disrupting the ANGPT/TEK receptor pathway could inhibit the growth of a
      number of murine tumors and human tumors. Thus, it is possible that inhibitors
      targeting the ANGPT/TEK pathway will have broad clinical utility to treatment of
      cancer.

PMID- 16456788
TI  - [A reverse transcriptase-polymerase chain reaction method improving the specific
      amplification of caveolin-1 gene sequences].
AB  - OBJECTIVE: To construct a reverse transcriptase-polymerase chain reaction (RT
      PCR)approach that can improve the specificity of primers while dropping down the
      nonspecific amplification. METHODS: In the recent study we reported a new RT-PCR
      assay which improved markedly the specificity. However its efficiency of
      regressing nonspecific amplification remains to be accurately checked and further
      documented. In primer design, we looked over again some sequences that showed
      differences at 5' or 3' ends between human CAV1 and mouse Cav1 genes. cDNAs and
      the diluted plasmids which harbored the sequence of human CAV1 or mouse Cav1 gene
      were chosen as the templates. The ordinary PCR compared with one, of which
      primers modified by phosphorothioate and combined with proofreading polymerase,
      for their efficiencies of nonspecific amplification inhibited. RESULTS: Taq DNA
      polymerase without proofreading activity could efficiently catalyze the extension
      of primers with a single or multiple mismatched base pairs at the 3' terminus,
      but the kind of primer extension can be effectively blocked by phosphorothioate
      modified primers combined with proofreading polymerase. Compared with ordinary
      PCR reaction, this new PCR method can effectively regress the primer mismatched
      amplification of 50 ng DNA almost equaling to 2 x 10(4) unmatched template copies
      in a final volume of 50 microL. CONCLUSION: Compared with the first generation of
      polymerases with or without proofreading activities mediating RT-PCR reaction,
      the introduction of nuclease-resistant 3' modified primers (3' phosphorothioate
      primer extension) can offer more simplicity, accuracy, and also decrease cost.

PMID- 16456790
TI  - [A new mutation of iduronate-2-sulfatase gene from the patient with Hunter
      syndrome].
AB  - OBJECTIVE: To identify the mutations of iduronate-2-sulfatase (IDS) gene, and to
      establish a basis of prenatal gene diagnosis of Hunter syndrome. METHODS: Urine
      glycosaminoglycan (GAG) assay was used to preliminary diagnosis of
      mucopolysaccharidosis. PCR-denaturing high-performance liquidchromatograptly (PCR
      DHPLC) analysis was performed to detect the mutation in exons 9, 3, 8 of the IDS
      gene. DNA sequencing was applied to analyze the mutation detected by PCR-DHPLC.
      RESULTS: Abnormal peaks were found by PCR-DHPLC. A new frame-mutation (1569+TT)
      in exon 9 of IDS gene was identified by DNA sequencing. Two "T"q inserted in
      position 1569 base pair (1569+TT) caused a substitution of codon 482 (TTA,
      leucine) to 482 (TTT, phenylalanine). The "TT" insertion results in the decrease
      of amino acids from 550 to 482. The patient is a hemizygote and his mother is a
      heterozygote. CONCLUSION: A new frame-shift mutation of IDS gene is found to
      report. The mutation (1569+TT) results in 68 amino acids lost. Probably it causes
      the enzyme activity seriously dropped down and being pathologically the basis of
      disease.

PMID- 16456791
TI  - [Genotype and phenotype analyses of three families with autosomal recessive
      juvenile parkinsonism].
AB  - OBJECTIVE: To investigate the gene mutations and the clinical features of Chinese
      patients with autosomal recessive juvenile parkinsonism(AR-JP). METHODS: the
      polymerase chain reaction (PCR), DNA sequence analysis, and restriction enzyme
      digestion analysis were applied to check parkin gene mutations of 15 index
      patients from 15 families with AR-JP. RESULTS: Three families were detected to
      have parkin mutations. Two of them had heterozygous deletion mutations (202-203
      del AG in exon 2, 1069-1074 del GTGTCC in exon 9) and another of them carried a
      heterozygous missense mutation [1422(T-->C) in exon 12]. Two of the mutations
      [1069-1074delGTGTCC and 1422(T-->C)] were not reported previously. There were six
      patients in the three families. Mean age at onset was 25.2+/-5.7 years, ranging
      from 18 to 31 years. The symptoms were under slow progression, diurnal
      fluctuation with sleep benefit, and hyperreflexia were relatively prominent.
      Response to levodopa was satisfactory. CONCLUSION: There are parkin mutations
      happened in Chinese patients with AR-JP. Patients with parkin mutations have
      distinct clinical features besides the common clinical features of Parkinson's
      disease.

PMID- 16456792
TI  - [Study on relationship between polymorphism sites of TIM-3 and allergic asthma in
      a population of adult Hans from Hubei province of China].
AB  - OBJECTIVE: To investigate two single nucleotide polymorphism sites of the
      promoter region in T cells immunoglobulin domain and mucin domain protein-3 (TIM
      3) and detect their relationship with allergic asthma in a population of adult
      Hans from Hubei province of China. METHODS: The polymorphisms were detected with
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      allelic specific polymerase chain reaction (ASPCR). The genotype and allele
      frequencies were calculated and analyzed. RESULTS: The genotype frequencies of
      CC, CT and TT in -1541 C/T polymorphism were 0.961, 0.039 and 0 respectively in
      the healthy population and were 0.935, 0.065 and 0 respectively in the allergic
      asthma population. No significant difference in genotype and alleles frequencies
      was found between the allergic asthma patients and control subjects (P=0.314,
      P=0.321). The genotype frequencies of GG, GT and TT in -574 T/G polymorphism were
      0.992, 0.008 and 0 respectively in the healthy population and were 0.941, 0.059
      and 0 respectively in the allergic asthma population. There was significant
      difference in genotype and allele frequencies between the allergic asthma
      patients and control subjects (P=0.046, P=0.048). CONCLUSION: There are
      polymorphism sites of the promoter region in TIM-3 , and one of these sites, the 
      574 G/T polymorphism site, may be associated with allergic asthma in the
      population of adult Hans from Hubei province of China.

PMID- 16456793
TI  - [The correlation between polymorphisms of matrix metalloproteinase-2 and -9 genes
      and colorectal cancer of Chinese patients].
AB  - OBJECTIVE: To investigate whether the polymorphisms of matrix metalloproteinase-2
      (MMP-2) and -9 (MMP-9) promoters contribute to the development and progression of
      colorectal cancer in Chinese population. METHODS: the PCR-based denaturing high
      performance liquid chromatography or PCR-restriction fragment length polymorphism
      technique respectively was applied to analyze the MMP-2 -1306C/T and MMP-9 
      1562C/T polymorphisms in normal group (126 individuals) and colorectal cancer
      group (126 cases). Genotype frequencies were compared between patients and
      matched controls, and the association of genotypes with clinical-pathological
      parameters was studied. RESULTS: The frequency of the CC genotype in the MMP-2
      gene polymorphism was significantly increased in colorectal cancer patients when
      compared with controls (P<0.05), and individuals with the CC genotype had an
      increased risk of developing colorectal cancer compared to those with CT+TT
      genotypes (OR: 1.959; 95%CI: 1.055-3.637). Significant correlation was found
      between the depth of tumor invasion and MMP-2 -1306C/T polymorphism in colorectal
      cancer patients. However, the genotype frequencies of MMP-9 -1562C/T in
      colorectal cancer patients were similar to those in control subjects. CONCLUSION:
      Our results indicate that MMP-2 -1306 C/T polymorphism may be associated with
      genetic susceptibility to colorectal cancer and the invasive capability of
      colorectal cancer in Chinese patients. And it is easier for the CC genotype
      cancer to invade through bowel wall.

PMID- 16456794
TI  - [Identification of three novel mutations of IRF6 in Chinese families with Van der
      Woude syndrome].
AB  - OBJECTIVE: To identify mutations of interferon regulatory factor 6 (IRF6) gene in
      Van der Woude syndrome (VWS) patients in China. METHODS: Three Chinese VWS
      families were screened to IRF6 gene mutation via PCR and sequence techniques.
      After amplification of exons 1-8 and their flanking splice junctions and part of
      exon 9 of the IRF6 gene by polymerase chain reaction, mutations were detected by
      direct sequencing. RESULTS: Three novel mutations, one in each family, were
      identified in all the affected members in the three families. There were one
      missense mutation 1214 (T-->C) in exon 9, two nonsense mutations 981 (T-->A) in
      exon 7 and 1234 (C-->T) in exon 9. All affected members of the three families
      were heterozygous for their respective mutation. CONCLUSION: Mutations in IRF6
      gene were found in all VWS patients. This observation supports the hypothesis
      that IRF6 is the gene responsible for VWS across different populations.

PMID- 16456795
TI  - [Association of the polymorphism in alpha-2 macroglobulin gene with essential
      tremor and Parkinson's disease].
AB  - OBJECTIVE: To study the association of two polymorphisms of alpha-2 macroglobulin
      gene (A2M), a 1000G/A in exon 24 and a pentanucleotide insertion/deletion (I/D)
      in the 5'splice site in exon 18, with Parkinson's disease (PD) and essential
      tremor (ET) in North China. METHODS: Using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method to investigate 87 cases of
      Parkinson's disease (PD),73 cases of ET and 100 randomly selected healthy control
      subjects. RESULTS: (1) The allelic and genotypic distributions of A2M G/A were
      significantly different among the PD, ET patients and controls (P<0.05). The
      allele G and genotype GA in PD patients were significantly higher than those in
      ET patients or controls (P<0.05). There was no statistically significant
      difference between ET patients and controls in allelic and genotypic distribution
      (P>0.05). (2) The differences in allelic and genotypic distributions of A2M I/D
      among PD, ET patients and selected controls were found to be of no statistical
      significance (P>0.05). CONCLUSION: (1) The polymorphism at the site of G/A might
      be associated with PD, but there might be no genetic association of polymorphism
      at this site with ET. (2) There might be no association of polymorphism at the
      site of I/D with PD and ET in North China.

PMID- 16456796
TI  - [The correlation between polymorphism at position -511C/T in the promoter region
      of interleukin 1B and the severity of coronary heart disease].
AB  - OBJECTIVE: To investigate the correlation between polymorphism at position 
      511C/T in the promoter region of interleukin 1B (IL1B) and the severity of
      coronary heart disease (CHD). METHODS: The polymerase chain reaction-restriction
      fragment length polymorphism technique was applied to analyze the polymorphisms
      of IL1B -511C/T in 127 patients with CHD and 152 controls. And the serum level of
      lipoproteins was detected by enzymology method. RESULTS: The distribution of IL1B
      -511C/T polymorphism between acute coronary syndrome (ACS) patients and controls
      was significantly different (chi-square test=5.72, P<0.01). CT and TT genotype
      carriers were in increased risk of ACS with more double ratio to CC genotype
      (OR=2.56, 95%CI=1.17-5.59). In CHD group, total cholesterol and low density
      lipoprotein-cholesterol levels of patients with CT and TT genotypes (6.09+/-0.97
      mmol/L and 3.97+/-0.92 mmol/L) were significantly higher than those of patients
      with CC genotype (5.12+/-0.56 mmol/L and 2.87+/-0.71 mmol/L, P<0.05). CONCLUSION:
      The polymorphism at position -511C/T in IL1B is associated with the severity of
      CHD, and the DNA variation at this position may affect the secretion of IL1B, and
      aggravate the reaction of inflammation and dyslipoidemia.

PMID- 16456797
TI  - [The analysis of HLA-A, B and DRB1 allelic polymorphism in Han race population in
      Lanzhou region of China].
AB  - OBJECTIVE: To investigate the HLA-A, B and DRB1 allele polymorphism of the Han
      race population in Lanzhou area. METHODS: Polymerase chain reaction-sequence
      specific primer was used to detect HLA-A, B and DRB1 alleles in 200 unrelated
      healthy Han individuals from Lanzhou region, Northwest China, and the results
      were compared with those of Han populations in North, South and Northwest China,
      and Hui, Uigur and Tibetan population in China. RESULTS: Fourteen of alleles were
      detected and identified for HLA-A; 32 for HLA-B; and 13 for HLA-DRB1. HLA- A*01,
      A*02,A*11,A*24, A*30, A*31, A*33; HLA- B*13, B*15, B*40, B*44, B*46, B*51, B*58,
      B*60; HLA- DRB1*04,. DRB1*07, DRB1*08, DRB1*09, DRB1*11, DRB1*12, DRB1*14 and
      DRB1*15 were the most common alleles. The frequencies of HLA-A, B and DRB1 genes
      of Lanzhou Han race were close to that of North China Hans and Hui population in
      Northwest China, and a little different to that of South China Hans. The HLA-DRB1
      alleles were significantly different to those of Uigur and Tibetan race
      population of China. CONCLUSION: The allelic polymorphism of HLA-A,B and DRB1
      loci of Han race population in Lanzhou area was between North and South Han race
      of China, close to Northwest China Hui, and markedly different to Northwest China
      Uigur and Tibetan race populations.

PMID- 16456798
TI  - [Genetic polymorphism of six short tandem repeat loci on the X chromosome in a
      Han race population in China].
AB  - OBJECTIVE: To investigate the alleles and genotype frequencies of 6 short tandem
      repeat (STR) loci DXS7130, DXS1214, DXS6799, DXS6804, DXS7424 and DXS7133 on the
      X chromosome in Chinese Han individuals living in Shaanxi province of Northwest
      China. METHODS: The 6 X-chromosomal STR loci were typed by PCR, denatured
      polyacylamide gel electrophoresis and silver stain. RESULTS: Among females from
      Xi'an Han population, the numbers of alleles in the 5 loci (DXS7130, DXS6799,
      DXS6804, DXS7424 and DXS7133) were detected to be 9, 6, 6, 7, and 7 respectively;
      the numbers of genotypes were 21, 14, 15, 17 and 12 respectively; and the number
      of alleles in the DXS1214 was 8. Exact tests demonstrated that genotype
      frequencies of females had no departure from Hardy-Weinberg equilibrium.
      CONCLUSION: The six loci of X-chromosomal STRs are appropriate for individual
      identification, paternity test involving in female child and for study in related
      disease.

PMID- 16456799
TI  - [HLA-DRB1 polymorphism in the Ewenki Ethnic of Inner Mongolian].
AB  - OBJECTIVE: To study the HLA-DRB1 genetic polymorphism in the Ewenki of Inner
      mongolia. METHODS: HLA-DRB1 allele polymorphisms in 84 normal Ewenki were
      determined by PCR with sequencing based typing (SBT). RESULTS: Twenty-five HLA
      DRB1 alleles were observed. The allele frequency of HLA-DRB1*03011(14.88%) is the
      highest; the allele frequencies of HLA -DRB1*09012 (13.69%), DRB1*07011(8.92%),
      DRB1*04011(9.52%) and DRB1*12011(8.33%) are lower. CONCLUSION: The distribution
      of HLA-DRB1 alleles frequencies in normal Ewenki from Inner Mongolia exhibits a
      unique profile, which is of important reference value for studies on anthropology
      and related illnesses in Ewenki population.

PMID- 16456800
TI  - [Genetic polymorphisms of 10 X chromosome STR loci in a Chinese Tibetan
      population].
AB  - OBJECTIVE: To investigate the alleles and genotypes frequency of 10 short tandem
      repeat (STR) loci on the X chromosome(DXS7423, DXS8378, DXS6799, DXS7424,
      DXS7130, DXS7132, DXS6789, DXS101, DXS6804, DXS7133) of Tibetan individuals
      living in Xizang Autonomous Region, Southwest China. METHODS: The 10 X
      chromosomal STR loci were analyzed with PCR, followed by polyacylamide gel
      electrophoresis and silver staining. RESULTS: Among unrelated Tibetan
      individuals, the numbers of alleles in the 10 X-STR loci(DXS7423, DXS8378,
      DXS6799, DXS7424, DXS7130, DXS7132, DXS6789, DXS101, DXS6804, DXS7133) were 5, 5,
      5, 9, 7, 7, 11, 9, 5 and 4, respectively. The genotype frequencies in females
      were in accordance with Hardy-Weinberg equilibrium. CONCLUSION: The 10 X
      chromosomal STRs loci are appropriate for individual identification, for
      paternity testing involving a female child, and for studies on related disease.

PMID- 16456801
TI  - Retraction: Studies on the genetic pathogenesis of myasthenia gravis caused by
      CTLA-4 gene polymorphism.

PMID- 16456802
TI  - [Single nucleotide polymorphisms and genotype combinations in calpain-10 gene of
      Korean population].
AB  - OBJECTIVE: This is an investigation made in Korean population with regard to the
      distribution of the single nucleotide polymorphisms (SNPs) in calpain-10 gene
      that was discovered in Mexican American. METHODS: By utilizing the techniques of
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),
      the authors analyzed the polymorphisms for calpain-10 SNP-43, -19 and -63
      genotype, evaluated the gene types, and calculated their frequencies and combined
      genotypes in 312 healthy Korean. RESULTS: The calpain-10 UCSNP-43 genotype
      frequencies for types 1/1, 1/2, and 2/2 were found to be 86.2%, 13.5%, and 0.3%
      respectively, with the allele frequencies 0.930 for G and 0.070 for A. The UCSNP
      19 genotype frequencies were 9.9% for type 1/1, 44.6% for type 1/2, 45.5% for
      type 2/2, with the allele frequencies 0.322 for D and 0.678 for I. The UCSNP-63
      genotype frequencies were 57.4% for type of 1/1, 35.9% for type of 1/2, 6.7% for
      type of 2/2, with the allele frequencies 0.754 for C and 0.246 for T. All of the
      gene distributions matched the equilibrium law of Hardy-Weinberg. A total of 12
      genotype combinations of three SNPs were observed in Korean. Seventy-five point
      six per cent of the Korean was composed of three genotype combinations in the
      order of UCSNP-43,-19 and -63, i.e., GG-DI-CC(haplotype combination 111/121,
      frequency=10.6%, GG-DI-CT(haplotype combination 112/121, frequency=28.8%), and GG
      II-CC(haplotype combination 121/121, frequency=36.2%). CONCLUSION: The
      distribution of SNPs in calpain-10 gene in Korean is similar to that in Chinese
      and Japanese, but different from that reported in Caucasian, American Mexicans
      and American Pima Indians.

PMID- 16456803
TI  - [HLA-A, B, DRB1 gene polymorphism of Beijing population was studied by high
      resolution polymerase chain reaction sequence-based typing].
AB  - OBJECTIVE: To investigate the gene polymorphism of human leukocyte antigen (HLA)
      A, B, DRB1 loci in the population of Beijing region, and research on the
      application feasibility of polymerase chain reaction sequence-based typing (PCR
      SBT) method. METHODS: PCR-SBT method was applied to determine HLA- A, B, DRB1
      genotypes of 618 unrelated healthy individuals of Beijing region. RESULTS: A
      total of 84 different alleles and 199 genotypes of HLA-A, 143 alleles and 366
      genotypes of HLA-B, 122 alleles and 286 genotypes of HLA-DRB1 were detected.
      CONCLUSION: The results showed the characteristics of HLA-A, B, DRB1
      distributions, and provided more comprehensive and accurate gene data that may
      serve as normal reference values for all of Beijing people.

PMID- 16456804
TI  - Complementary structural information of positive- and negative-ion MSn spectra of
      glycopeptides with neutral and sialylated N-glycans.
AB  - Positive- and negative-ion MSn spectra of chicken egg yolk glycopeptides binding
      a neutral and a sialylated N-glycan were acquired by using electrospray
      ionization linear ion trap time-of-flight mass spectrometry (ESI-LIT-TOFMS) and
      collision-induced dissociation (CID) with helium as collision gas. Several
      characteristic differences were observed between the positive- and negative-ion
      CID MSn (n = 2, 3) spectra. In the positive-ion MS2 spectra, the peptide moiety
      was presumably stable, but the neutral N-glycan moiety caused several B-type
      fragmentations and the sialylated N-glycan almost lost sialic acid(s). In
      contrast, in the negative-ion MS2 spectra, the peptide moiety caused several side
      chain and N-glycan residue (e.g., N-acetylglucosamine (GlcNAc) residue)
      fragmentations in addition to backbone cleavages, but the N-glycan moieties were
      relatively stable. The positive-ion MS3 spectra derived from the protonated
      peptide ion containing a GlcNAc residue (203.1 Da) provided enough information to
      determine the peptide amino-acid sequence including the glycosylation site, while
      the negative-ion MS3 spectra derived from the deprotonated peptide containing a
      0,2X1-type cross-ring cleavage (83.1 Da) complicated the peptide sequence
      analysis due to side-chain and 0,2X1 residue related fragmentations. However, for
      the structural information of the N-glycan moiety of the glycopeptides, the
      negative-ion CID MS3 spectra derived from the deprotonated 2,4A6-type cross-ring
      cleavage ion (neutral N-glycan) or the doubly deprotonated B6-type fragment ion
      (sialylated N-glycan) are more informative than are those of the corresponding
      positive-ion CID MS3 spectra. Thus, the positive-ion mode of CID is useful for
      the analyses of peptide amino-acid sequences including the glycosylation site.
      The negative-ion mode of CID is especially useful for sialylated N-glycan
      structural analysis. Therefore, in the structural analysis of N-glycopeptides,
      their roles are complementary.

PMID- 16456805
TI  - 2,5-Dihydroxyacetophenone: a matrix for highly sensitive matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometric analysis of proteins
      using manual and automated preparation techniques.
AB  - 2,5-Dihydroxyacetophenone (DHAP) is presented as a matrix which enables highly
      sensitive matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
      mass spectrometric analysis of peptides, proteins and glycoproteins on AnchorChip
      targets. Depending on the protein, lower fmol amounts can be detected due to the
      increased homogeneity and concentration of the crystallization of the
      analyte/matrix mixture on the anchors. Best results could be generated in the
      mass range of 8-100 kDa. All sample/matrix preparation steps starting from mixing
      of DHAP matrix solution with sample solution to the transfer of the mixture to
      the MALDI-TOF target can be performed manually or automatically allowing low- and
      high-throughput analyses.

PMID- 16456806
TI  - Simultaneous quantitative determination of cyclosporine A and its three main
      metabolites (AM1, AM4N and AM9) in human blood by liquid chromatography/mass
      spectrometry using a rapid sample processing method.
AB  - We have developed a sensitive and specific liquid chromatography/mass
      spectrometry (LC/MS) method for the simultaneous determination of cyclosporine A
      (CsA) and its three main metabolites (AM1, AM4N and AM9) in human blood.
      Following protein precipitation, supernatant was directly injected into the LC/MS
      system. Chromatographic separation was accomplished on a Symmetry C8 (4.6 x 75
      mm, 3.5 microm) column with a linear gradient elution prior to detection by
      atmospheric pressure chemical ionization (APCI) MS using selected ion monitoring
      (SIM) in positive mode. This method can be applied to single mass equipment. The
      analytical range for each analyte was set at 1-2500 ng/mL using 100 microL of
      blood sample. The analytical method was fully validated according to FDA
      guidance. Intra-day mean accuracy and precision were 95.2-113.5% and 0.9-8.9%,
      respectively. Inter-day mean accuracy and precision were 95.8-107.0% and 1.5
      10.7%, respectively. In blood all analytes were stable during three freeze/thaw
      cycles, for 24 h at room temperature and for 12 months at or below -15 degrees C.
      Stability was also confirmed in processed samples for 24 h at 10 degrees C and
      for 6 months at 4 degrees C in methanol. In addition, we confirmed the method
      could avoid matrix effects from transplant subjects' samples. This LC/MS
      technique provided an excellent method for simultaneous quantitative
      determination of CsA and its three metabolites for evaluation of their
      pharmacokinetic profiles.

PMID- 16456807
TI  - Magnetic resonance-guided, vacuum-assisted breast biopsy: results from a European
      multicenter study of 538 lesions.
AB  - BACKGROUND: The objective of this study was to determine the accuracy,
      reproducibility, and clinical value of magnetic resonance (MR)-guided, vacuum
      assisted breast biopsy (MR-VAB) in a prospective, multicenter study. METHODS: In
      5 European centers, MR-VAB was performed or attempted on 538 suspicious lesions
      that were visible or could targeted only by MR imaging (MRI). Verification of
      malignant or borderline lesions included reexcision of the biopsy cavity. Benign
      biopsy results were verified by retrospective correlation of histology with
      preinterventional and postinterventional MRI studies. Follow-up of 24-48 months
      (median, 32 months) was available for 491 of 538 patients. RESULTS: MR-VAB was
      unsuccessful or was not completed in 21 of 538 patients, for which an immediate
      repeat biopsy was recommended. Five hundred seventeen of 538 performed VAB
      procedures (96%) were successful. Histology yielded 138 (27%) malignancies, 17
      (3%) atypical ductal hyperplasias, and 362 (70%) benign entities. No false
      negative diagnoses occurred among the 517 successful MR-VAB procedures. The
      positive predictive value of VAB depended on patient preselection, which differed
      according to the indication for the initial MRI study. CONCLUSIONS: The results
      of this study indicated that MR-VAB offers excellent accuracy. Small lesion size
      did not prove to be a limitation.

PMID- 16456808
TI  - Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts
      the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based
      chemotherapy.
AB  - BACKGROUND: In the current Phase II study, the authors evaluated the association
      between genomic polymorphic variants in uridine diphosphate glucuronosyl
      transferase (UGT1A1), methylenetetrahydrofolate reductase (MTHFR), and
      thymidylate synthase (TS) genes, and the incidence of the adverse effects of
      irinotecan and raltitrexed in previously heavily treated patients with metastatic
      colorectal carcinoma. METHODS: Fifty-six patients received irinotecan (at a dose
      of 80 mg/m(2) on Days 1, 8, 15, and 22 every 5 wks), combined with raltitrexed
      (at a dose of 3 mg/m(2) every 3 wks). Genotyping for the MTHFR C677T
      polymorphism, the TATA box region in the UGT1A1 promoter, and tandem repeats in
      the TS promoter was performed on genomic DNA extracted from blood. Nineteen
      variables related to patient, disease, and treatment characteristics, together
      with genotypes, were analyzed using a binary logistic regression model with
      stepwise selection to evaluate their correlation with adverse reactions. RESULTS:
      Toxicities (determined according to the National Cancer Institute Common Toxicity
      Criteria) were evaluated in 169 cycles. Grade 3/4 neutropenia was reported to
      occur in 2% of cycles, Grade 2-4 nausea was reported to occur in 19% of cycles,
      Grade 2-4 emesis was reported to occur in 9% of cycles, Grade 2-4 diarrhea was
      reported to occur in 20% of cycles, Grade 2/3 fatigue was reported to occur in
      11% of cycles, and Grade 3/4 hepatic toxicity was reported to occur in 7% of
      cycles. Homozygosis for six TA repeats in the promoter region of the UGT1A1 gene
      was found to be the main predictive factor for diarrhea (P < 0.00005), emesis (P
      = 0.0001), and fatigue (P = 0.007). Homozygosis for two tandem repeats in the TS
      promoter was found to be predictive of a reduced incidence of fatigue (P =
      0.044). MTHFR C677T polymorphism was not found to be associated with any adverse
      reaction. CONCLUSIONS: In the current study, UGT1A1 promoter polymorphism was
      found to be predictive of the risk of diarrhea, emesis, and fatigue caused by
      chemotherapy with irinotecan and raltitrexed. Screening for UGT1A1 promoter
      polymorphism may be clinically useful for identifying patients at a higher risk
      of developing a severe or potentially life-threatening toxicity after irinotecan
      based chemotherapy.

PMID- 16456809
TI  - The number of lymph nodes with metastasis predicts survival in patients with
      esophageal or esophagogastric junction adenocarcinoma who receive preoperative
      chemoradiation.
AB  - BACKGROUND: The survival of patients with locoregional adenocarcinoma of the
      esophagus or the esophagogastric junction (EGJ) who receive preoperative
      chemoradiation is reported to be better among patients who achieve a pathologic
      complete response than among patients who have residual tumor, including lymph
      node (LN) metastasis. However, the prognostic significance of the number of LNs
      with residual metastasis remains unclear. METHODS: The authors studied 187
      consecutive patients who received chemoradiation followed by an esophagectomy.
      The number of positive LNs and the size of metastatic tumor in each positive LN
      were examined with regard to overall survival (OS) and recurrence-free survival
      (RFS). RESULTS: A pathologic complete response was achieved by 29% of patients.
      No LN metastasis (posttherapy pathologic negative LN status [ypN0]) was present
      in 49% of patients who had residual carcinoma, and LN metastasis (ypN1) was
      present in 51% of patients. The 5-year OS and 2-year RFS rates achieved by
      patients who had 1 positive LN (34% and 45%, respectively) were similar to the
      rates achieved by patients in the ypN0 group (38% [P = 0.84] and 50% [P = 0.77],
      respectively) but were significantly better than the rates achieved by patients
      who had > or = 2 positive LNs (6% [P = 0.02] and 18% [P = 0.01], respectively).
      The size of metastatic tumor in LNs among patients who had 1 positive LN was a
      prognostic factor (> or = 4 mm vs. < 4 mm; P = 0.04). In multivariate analysis,
      OS was better in patients who had 1 LN metastasis among patients in the ypN1
      group (P = 0.02) independent of their posttherapy pathologic tumor status.
      CONCLUSIONS: The current results suggested that the number of LNs with metastasis
      is an independent prognostic factor in patients with residual adenocarcinoma of
      the esophagus or the EGJ after preoperative chemoradiation. The authors suggest
      modification of the tumor-lymph node-metastasis (TNM) staging classification
      (ypTNM) to include the number of positive LNs in the ypN1 category.

PMID- 16456810
TI  - K-ras mutations in incident sporadic colorectal adenomas.
AB  - BACKGROUND: Although K-ras is the most frequently mutated protooncogene in
      colorectal carcinoma, the specific role and timing of K-ras mutations in
      colorectal carcinogenesis remains controversial. In the current study, the
      authors investigated associations with K-ras mutation in incident sporadic
      colorectal adenomas that occurred during a chemoprevention trial of calcium
      supplementation. METHODS: K-ras genotyping was performed on 303 colorectal
      adenomas that were removed from 207 participants during the follow-up phase of
      the Calcium Polyp Prevention Study. Mutations in codons 12 or 13 of K-ras were
      detected by denaturing high-performance liquid chromatography and were confirmed
      by direct sequencing. RESULTS: The adenomas analyzed had a mean estimated size of
      0.5 cm, and 3.0% were identified with mutations (95% confidence interval [95%
      CI], 1.3-4.4%). These mutations were more common in larger adenomas (risk ratio
      [RR], 12.7 for tumors that measured > 0.5 cm vs. < or = 0.5 cm; 95% CI, 2.7
      59.7), in adenomas with more advanced histology (RR, 20.6 for
      tubulovillous/villous vs. tubular; 95% CI, 4.4-96.0), and in adenomas that were
      located in the rectum compared with the colon (RR, 8.4; 95% CI, 2.3-30.5).
      CONCLUSIONS: Compared with previous studies, the current analysis was novel,
      because it focused on incident adenomas that were diagnosed within a few years of
      a previous "clean" colonoscopy. The results provided evidence for a very low rate
      of K-ras mutation among these small, early adenomas and strong support for a role
      of K-ras mutations in adenoma progression.

PMID- 16456811
TI  - First- and second-line chemotherapy with docetaxel or mitoxantrone in patients
      with hormone-refractory prostate cancer: does sequence matter?
AB  - BACKGROUND: Docetaxel and mitoxantrone are considered first-line chemotherapeutic
      options in patients with hormone-refractory prostate cancer (HRPC), but their
      clinical effectiveness in a second-line setting is unknown. Therefore, the
      authors conducted a population-based retrospective study to establish activity
      and tolerability of second-line docetaxel or mitoxantrone in HRPC. METHODS: The
      study included 68 patients who had failed androgen ablation therapy and who
      received docetaxel and mitoxantrone in either sequence. Clinical efficacy in
      terms of median overall survival (OS), progression-free survival (PFS),
      posttreatment prostate-specific antigen (PSA) decline of > or = 50% and treatment
      related toxicity were evaluated. RESULTS: Of 68 patients, 35 received docetaxel
      followed by mitoxantrone, and 33 received mitoxantrone followed by docetaxel.
      Both groups were comparable for recognized pretreatment prognostic factors.
      Patients who received docetaxel first-line had a trend toward longer median OS
      compared with patients treated with second-line docetaxel after mitoxantrone
      failure (22 mos, 95% confidence interval [CI], 17.2-26.8 mos vs. 15 mos, 95% CI,
      10.4-19.6 mos). Median number of second-line chemotherapy cycles was 3 and median
      PFS survival was 2-3 months in both groups. Second-line docetaxel produced a
      higher PSA response compared with mitoxantrone (38% vs. 12%, P = 0.012), but this
      did not translate to a survival benefit. Both second-line docetaxel and
      mitoxantrone were associated with a high frequency of treatment-related adverse
      events that resulted in dose reduction, delay, or discontinuation (64% and 46% of
      patients, respectively). CONCLUSIONS: Study results favored docetaxel given up
      front for patients with HRPC considered suitable for further chemotherapy. Second
      line docetaxel or mitoxantrone had limited efficacy and tolerability. Patients
      who are candidates for second-line chemotherapy, should be enrolled into clinical
      trials.

PMID- 16456812
TI  - Critical analysis of prostate-specific antigen doubling time calculation
      methodology.
AB  - BACKGROUND: Prostate-specific antigen (PSA) doubling time (PSADT) has emerged as
      an important surrogate marker of disease progression and survival in men with
      prostate carcinoma. The literature is replete with different methods for
      calculating PSADT. The objective of the current study was to identify the method
      that best described PSA growth over time and predicted disease-specific survival
      in men with androgen-independent prostate carcinoma. METHODS: PSADT was
      calculated for 122 patients with androgen-independent prostate carcinoma using 2
      commonly used methods: best-line fit (BLF) and first and last observations (FLO).
      Then, PSADT was calculated by using both a random coefficient linear (RCL) model
      and a random coefficient quadratic (RCQ) model. Statistical analysis was used to
      compare the ability of the methods to fit the patients' PSA profiles and to
      predict disease-specific survival. RESULTS: The RCQ model provided the best fit
      of the patients' PSA profiles, as determined according to the significance of the
      added parameters for the RCQ equation (P < or = 0.002). The PSADT estimates from
      the FLO method, the RCL model, and the RCQ model were highly significant
      predictors (P < 0.001) of disease-specific survival, whereas estimates from the
      BLF method were not found to be significant predictors (P = 0.66). PSADT
      estimates from the RCQ and RCL models provided an improved correlation of disease
      specific survival (both R(2) = 0.55) compared to the FLO (R(2) = 0.11) and BFL
      (R(2) = 0.003) methods. CONCLUSIONS: Random coefficient methods provided a more
      reliable fit of PSA profiles than other models and were superior to other
      available models for predicting disease-specific survival in patients with
      androgen-independent prostate carcinoma. The authors concluded that consideration
      should be given to applying the RCL or RCQ models in future assessments of PSADT
      as a predictive parameter.

PMID- 16456813
TI  - Expression of FasL in squamous cell carcinomas of the cervix and cervical
      intraepithelial neoplasia and its role in tumor escape mechanism.
AB  - BACKGROUND: To date, several mechanisms have been described by which malignant
      cells escape from the immune system. One of these is through the expression of
      FasL. The authors hypothesized that the Fas/FasL interaction enables cervical
      carcinoma cells to induce apoptosis of the cells of the immune system and thereby
      escape from them. METHODS: The authors tested the expression of FASL on the
      surface of cervical carcinoma tissues. Next, they stained the same cervical
      tissues with anti-human leukocyte common antigen and TUNEL to identify apoptotic
      cells. An in vitro functional assay was then done to test if the FASL expressed
      on the surface of cervical carcinoma cell lines was or was not responsible for
      inducing apoptosis in T-cells. Finally, they compared the expression of FASL on
      normal and dysplastic cervical tissues. RESULTS: Ninety-four percent of the
      cervical carcinoma tissues the authors tested expressed FasL and the majority of
      the apoptotic cells in the specimens were leukocytes with very few tumor cells.
      In the in vitro functional assay, only the Fasl expressing cell line and not the
      Fasl negative cell line was able to induce apoptosis of the Fas-expressing Jurkat
      cells. On examining the normal cervical tissues, the authors found that the
      expression of Fasl was confined to the basal cell layer with loss of expression
      observed in the suprabasal layers, which made it an immune privileged site.
      Conversely, there was persistent expression of FasL in the dysplastic layers in
      cervical dysplasia and squamous cell carcinoma specimens. CONCLUSIONS: The
      findings of the current study support the authors' hypothesis that persistent
      expression of FasL plays a role in the ability of cervical carcinoma cells to
      escape from the immune system.

PMID- 16456814
TI  - Second autologous or allogeneic transplantation after the failure of first
      autograft in patients with multiple myeloma.
AB  - BACKGROUND: Most patients undergoing high-dose therapy and autologous transplant
      for multiple myeloma eventually develop a disease recurrence. However, to the
      authors' knowledge, the optimal salvage treatment for these patients is not well
      defined. Both autologous and allogeneic hematopoietic stem cell transplantations
      have been used for salvage therapy. The outcomes of salvage autologous or
      allogeneic transplants were analyzed retrospectively in patients relapsing after
      an autograft. METHODS: Fourteen patients (median age, 52 yrs) received a second
      autograft for salvage, whereas 26 patients (median age, 51 yrs) underwent a
      reduced-intensity allogeneic transplantation (related in 18 patients and
      unrelated in 8 patients). The median interval between the first and the second
      transplant was 25 months in the autologous group and 17 months in the allogeneic
      group. The two groups were evenly matched with regard to other disease
      characteristics. RESULTS: After a median follow-up of 18 months for the
      autologous group and 30 months for the allogeneic group, the median progression
      free survival (PFS) and overall survival (OS) in the 2 groups were 6.8 months
      versus 7.3 months and 29 months versus 13 months, respectively. Acute and chronic
      graft versus host disease (15%) was the most common cause of non-recurrence
      mortality in the allogeneic group and infections (14%) in the autologous group.
      On univariate analysis, an interval of > 1 year between the first and the salvage
      transplant predicted a better OS in the allogeneic group. CONCLUSIONS: Both
      autografting and allografting are feasible as salvage therapy for myeloma
      patients who develop disease recurrence after the first autograft, although
      disease progression remains the major cause of failure. Better approaches are
      needed for salvage therapy in patients developing disease recurrence after an
      autograft.

PMID- 16456815
TI  - Nuclear expression of the antiapoptotic protein survivin in malignant melanoma.
AB  - BACKGROUND: Expression of the antiapoptotic protein survivin has been
      demonstrated in some melanocytic lesions and is believed to be required for
      melanoma cell viability. However, its diagnostic value in differentiating
      melanomas from nevi has not yet been examined. METHODS: Tissue microarray blocks
      were constructed with paraffin-fixed tissue of 19 nevi, 18 dysplastic nevi, 24
      malignant melanomas, and 31 metastatic melanomas. Sections were then reacted with
      three antisurvivin antibodies (two monoclonal and one polyclonal) assessing
      labeling intensity (absent or weak, and moderate to strong) as well as the
      percentage of cells labeled (< 25%, > or = 25%). RESULTS: Of the antibodies
      evaluated, the polyclonal one was found to be the most sensitive. Nuclear
      immunoreactivity for survivin (i.e., > or = 25% of cells exhibiting and/or at
      least moderately intense staining) was seen in a subset of melanomas but not in
      nevi or dysplastic nevi (P < 0.05). CONCLUSIONS: Survivin is variably expressed
      in the cytoplasm in the entire spectrum of melanocytic lesions, with nuclear
      expression detectable only in melanomas. These data may underscore the importance
      of nuclear survivin in progression to melanoma and may prove useful in the
      differential diagnosis of melanoma versus nevus.

PMID- 16456816
TI  - Elevated serum level of YKL-40 is an independent prognostic factor for poor
      survival in patients with metastatic melanoma.
AB  - BACKGROUND: YKL-40 is a growth factor for connective tissue cells and stimulates
      migration of endothelial cells. Cancer cells, macrophages, and neutrophils
      secrete YKL-40. Its function in cancer is unknown. High serum YKL-40 levels have
      been associated with a poor prognosis in patients with several solid tumors. The
      prognostic impact of serum YKL-40 in metastatic melanoma was evaluated. METHODS:
      YKL-40 was measured in serial serum samples from 110 patients with metastatic
      melanoma obtained immediately before and during treatment and from 245 healthy
      subjects. RESULTS: Patients had higher serum YKL-40 values than healthy subjects
      (P < 0.001). Pretreatment serum YKL-40 was elevated in 45% of the patients and
      correlated to site of metastases (P = 0.03) and poor performance status (P =
      0.002). Multivariate Cox analysis showed that serum YKL-40 (hazard ratio [HR] =
      1.9; 95% confidence interval [CI], 1.2-2.8; P = 0.004) and serum lactate
      dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2-2.9; P = 0.004) were independent
      prognostic factors for survival. A combination variable of elevated serum YKL-40
      and LDH quadrupled the risk of early death (HR = 4.4; 95% CI, 2.5-7.7; P < 0.001)
      compared with patients with normal levels. The combination of YKL-40 and LDH had
      a stronger prognostic impact than the American Joint Committee on Cancer (AJCC)
      Stage IV classification. Furthermore, serum samples were available from 12
      patients during followup. In 9 of 11 patients a significant increase in serum YKL
      40 was observed together with disease progression. In one patient with a lasting
      complete response, serum YKL-40 remained normal. CONCLUSIONS: An elevated serum
      YKL-40 was an independent prognostic factor for poor survival in patients with
      metastatic melanoma. When combining serum YKL-40 and LDH, patients could be
      separated into three prognostic groups based on the number of elevated
      biomarkers. The findings should be validated in an independent study.

PMID- 16456817
TI  - Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion:
      analysis of morbidity and mortality in 209 peritoneal surface malignancies
      treated with closed abdomen technique.
AB  - BACKGROUND: The purpose of this prospective Phase II study was to analyze
      morbidity and mortality of cytoreductive surgery (CRS) and intraperitoneal
      hyperthermic perfusion (IPHP) in the treatment of peritoneal surface
      malignancies. METHODS: A total of 205 patients (50 with peritoneal mesothelioma,
      49 with pseudomyxoma peritonei, 41 with ovarian cancer, 32 with abdominal
      sarcomatosis, 13 with colon cancer, 12 with gastric cancer, and 8 with
      carcinomatosis from other origins) underwent 209 consecutive procedures. Four
      patients underwent the intervention twice because of disease relapse. There were
      70 men and 135 women. Mean age was 52 years (range, 22-76 yrs). CRS was performed
      by using peritonectomy procedures. IPHP through the closed abdomen technique was
      conducted with a preheated (42.5 degrees C) perfusate containing cisplatin +
      mitomycin C or cisplatin + doxorubicin. RESULTS: Major morbidity rate was 12%.
      The most significant complications were 23 anastomotic leaks or bowel
      perforations, 4 abdominal bleeds, and 4 sepses. Operative mortality rate was
      0.9%. On logistic regression model multivariate analysis, extent of cytoreduction
      (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.29-6.40) and dose of
      cisplatin for IPHP > or = 240 mg (OR, 3.13; 95% CI, 1.24-7.90) were independent
      risk factors for major morbidity. Ten patients presented with Grade 3 to 4
      toxicity. CONCLUSIONS: CRS + IPHP presented acceptable morbidity, toxicity, and
      mortality rates, all of which support prospective Phase III clinical trials.

PMID- 16456818
TI  - Motion correction and the use of motion covariates in multiple-subject fMRI
      analysis.
AB  - The impact of using motion estimates as covariates of no interest was examined in
      general linear modeling (GLM) of both block design and rapid event-related
      functional magnetic resonance imaging (fMRI) data. The purpose of motion
      correction is to identify and eliminate artifacts caused by task-correlated
      motion while maximizing sensitivity to true activations. To optimize this
      process, a combination of motion correction approaches was applied to data from
      33 subjects performing both a block-design and an event-related fMRI experiment,
      including analysis: (1) without motion correction; (2) with motion correction
      alone; (3) with motion-corrected data and motion covariates included in the GLM;
      and (4) with non-motion-corrected data and motion covariates included in the GLM.
      Inclusion of covariates was found to be generally useful for increasing the
      sensitivity of GLM results in the analysis of event-related data. When motion
      parameters were included in the GLM for event-related data, it made little
      difference if motion correction was actually applied to the data. For the block
      design, inclusion of motion covariates had a deleterious impact on GLM
      sensitivity when even moderate correlation existed between motion and the
      experimental design. Based on these results, we present a general strategy for
      block designs, event-related designs, and hybrid designs to identify and
      eliminate probable motion artifacts while maximizing sensitivity to true
      activations.

PMID- 16456819
TI  - Low-field compact magnetic resonance imaging system for the hand and wrist in
      rheumatoid arthritis.
AB  - PURPOSE: To investigate the feasibility of an originally developed compact MRI
      system for evaluating rheumatoid arthritis (RA), and determine its advantages and
      disadvantages as an imaging modality for evaluating RA. MATERIALS AND METHODS: We
      prospectively studied 13 healthy controls with no clinical symptoms of arthritis,
      and 13 patients with hand and wrist pains (including pain from RA) with a 0.2 T
      permanent-magnet compact MR imager. All MR images were obtained while the
      subjects were in a sitting position. Coronal three-dimensional spin-echo T1
      weighted images and coronal two-dimensional short tau inversion recovery (STIR)
      images were obtained with image matrix = 256 x 128 and field of view (FOV) =
      20.48 cm. Plain radiograph findings and MRI findings of patients were compared.
      RESULTS: In three of the patients with suspected early RA (N = 7), early RA was
      evaluated based on STIR images. All RA patients showed morphologic or signal
      intensity changes that allowed an evaluation of RA from MR findings. Four of five
      RA patients showed high signal intensity on STIR images in the wrist, proximal
      interphalangeal (PIP) joint, or metacarpophalangeal (MCP) joint that suggested
      synovitis. Multiple erosions in the hand and wrist were seen in four RA patients,
      with low signal intensity on T1-weighted images. CONCLUSION: RA was correctly
      evaluated, and early RA could be identified with the compact MRI system. However,
      the current system has limitations, such as the nonselective STIR sequence used
      and magnetic field inhomogeneity.

PMID- 16456821
TI  - Partial-volume model for determining white matter and gray matter cerebral blood
      volume for analysis of gliomas.
AB  - PURPOSE: To model the partial voluming of gray matter (GM) and white matter (WM)
      in perfusion imaging, and to use this model to estimate the cerebral blood volume
      (CBV) of pure WM and GM, which could then be used to normalize data across
      patients in preparation for analyzing tumor perfusion. MATERIALS AND METHODS:
      Dynamic susceptibility contrast (DSC) perfusion imaging was performed on 20
      glioma patients. The perfusion data were registered to the T1 image using rigid
      body and non-rigid algorithms. The rCBV for each voxel was computed by gamma
      variate fitting and then fit as a linear function of the estimated fractional WM
      content. The estimated CBV of pure WM was used to normalize across patients, and
      the resulting tumor CBV values were compared with expectations. RESULTS: Rigid
      registration improved the correlation between the fractional WM content and CBV
      for all patients, with non-rigid registration yielding further improvements for
      all but two patients. The mean GM-to-WM CBV ratio was estimated at 2.15 +/- 0.33
      (mean +/- SD). Voxels that exhibited both T1-Gd contrast enhancement and an
      abnormal proton spectrum were found to have a CBV 2.53 +/- 0.89 times higher than
      that in the WM. CONCLUSION: A partial-volume model is demonstrated for estimating
      pure WM and GM CBV. It is also shown that the relationship between the tumor CBV
      as estimated with this model is generally consistent with expectations based on
      spectroscopy and imaging.

PMID- 16456820
TI  - Effect of Gd-DTPA-BMA on blood and myocardial T1 at 1.5T and 3T in humans.
AB  - PURPOSE: To compare T(1) values of blood and myocardium at 1.5T and 3T before and
      after administration of Gd-DTPA-BMA in normal volunteers, and to evaluate the
      distribution of contrast media between myocardium and blood during steady state.
      MATERIALS AND METHODS: Ten normal subjects were imaged with either 0.1 mmol/kg (N
      = 5) or 0.2 mmol/kg (N = 5) of Gd-DTPA-BMA contrast agent at 1.5T and 3T. T(1)
      measurements of blood and myocardium were performed prior to contrast injection
      and every five minutes for 35 minutes following contrast injection at both field
      strengths. Measurements of biodistribution were calculated from the ratio of
      DeltaR(1) (DeltaR(1myo)/DeltaR(1blood)). RESULTS: Precontrast blood T(1) values
      (mean +/- SD, N = 10) did not significantly differ between 1.5T and 3T (1.58 +/-
      .13 sec, and 1.66 +/- .06 sec, respectively; P > 0.05), but myocardium T(1)
      values were significantly different (1.07 +/- .03 sec and 1.22 +/- .07 sec,
      respectively; P < 0.05). The field-dependent difference in myocardium T(1)
      postinjection (T(1)@3T - T(1)@1.5T) decreased by approximately 72% relative to
      precontrast T(1) values, while the field-dependent difference of blood T(1)
      decreased only 30% postcontrast. Measurements of DeltaR(1myo)/DeltaR(1blood) were
      constant for 35 minutes postcontrast, but changed between 1.5T and 3T (0.46 +/-
      .06 vs. 0.54 +/- .06, P < 0.10). CONCLUSION: T(1) is significantly longer for
      myocardium (but not blood) at 3T compared to 1.5T. The differences in T(1) due to
      field strength are reduced following contrast administration, which may be
      attributed to changes in DeltaR(1myo)/DeltaR(1blood) with field strength.

PMID- 16456822
TI  - Papillary renal carcinoma: diagnostic approach by chemical shift gradient-echo
      and echo-planar MR imaging.
AB  - PURPOSE: To elucidate whether MRI can detect fat in interstitial histiocytes and
      hemosiderin (Hs) deposition (both of which are histological characteristics of
      papillary renal carcinoma (RCpap)) within RCpap. MATERIALS AND METHODS:
      Preoperative MR images of nine surgically confirmed RCpap and 57 clear cell renal
      carcinoma (RCcc) cases were retrospectively studied. Solid components of the
      lesions were evaluated. For fat detection, signal reduction on opposed-phase
      images of chemical shift MRI (CSI) was used. For Hs detection, signal reduction
      on echo-planar images or in-phase images of CSI was used. The prevalence of fat
      and Hs detection was compared between RCpap and RCcc. RESULTS: In five of nine
      RCpap (54%), and 38 of 57 RCcc (67%), the presence of fat within the tumor was
      suggested by CSI (P = 0.71). Hs deposition within tumors was suggested by either
      EPI or CSI in nine of nine RCpap (100%), and 28 of 57 RCcc (51%) (P = 0.0036). Hs
      in RCpap was observed without or apart from necrosis or hemorrhage, whereas Hs in
      RCcc was located predominantly around necrosis. CONCLUSION: Detecting
      intratumoral Hs by EPI or CSI, particularly that unrelated to necrosis or
      hemorrhage, may help differentiate RCpap from RCcc.

PMID- 16456823
TI  - B(0) homogeneity throughout the monkey brain is strongly improved in the sphinx
      position as compared to the supine position.
AB  - PURPOSE: To map B(0) distortions throughout the monkey brain in the two positions
      commonly used for NMR studies (the prone sphinx position and the supine position)
      in order to test the hypothesis that B(0) homogeneity in the sphinx position is
      significantly improved as compared to the supine position. MATERIALS AND METHODS:
      Three macaque monkeys were installed in the two positions in a 3T whole-body MR
      system without shim correction. B(0) maps were acquired using a 3D gradient
      double-echo sequence, and field dispersion throughout the brain was quantified.
      In addition, field maps and localized (1)H spectra were acquired after first
      order shimming was performed. RESULTS: The field maps collected in the three
      animals were highly reproducible. B(0) dispersion throughout the brain was
      typically two to three times greater in the supine position than in the sphinx
      position. Although first-order shimming proved relatively more efficient in the
      supine position, B(0) dispersion still remained greater in the supine than in the
      sphinx position. These findings can be explained by the thickness of outer brain
      tissues. CONCLUSION: This work demonstrates that the sphinx position is highly
      favorable in terms of B(0) homogeneity. It should prove useful for NMR
      exploration of the monkey brain, particularly at high fields where B(0)
      inhomogeneity associated with susceptibility artifacts is increased.

PMID- 16456824
TI  - Elimination of residual blood flow-related signal in 3D volume-selective TSE
      arterial wall imaging using velocity-sensitive phase reconstruction.
AB  - PURPOSE: To improve 3D volume-selective turbo spin-echo (TSE) arterial wall
      imaging by introducing velocity phase sensitivity to the sequence. MATERIALS AND
      METHODS: Slow or recirculating blood may give incomplete nulling in 3D vessel
      wall imaging, hindering differentiation between arterial wall and lumen.
      Reconstructed phase images are used to reduce the residual blood signal with
      postprocessing. A volume-selective 3D TSE (1) sequence with increased velocity
      sensitivity perpendicular to the slab was developed. Sensitivity was introduced
      by modifying the gradient waveforms such that residual signal from slow or
      recirculating blood is distinguished from the wall by the phase shift introduced.
      This was tested on a pulsatile flow phantom and the carotid artery wall of six
      healthy volunteers and 17 patients. Images were acquired on a Siemens Magnetom
      Sonata 1.5T scanner. A quantitative comparison of the lumen/wall contrast was
      made using images acquired with and without modification. RESULTS: Velocity
      sensitivity produces significantly reduced residual signal by intravoxel
      dephasing. Phantom "lumen/tissue" contrast improved by 0.10 (P < 0.01), with a
      similar change in vivo (0.69-0.73, P < 0.01). Postprocessing removal of the blood
      signal using phase signal provided further improvement. CONCLUSION: Introducing
      velocity sensitivity reduces unwanted, potentially misleading residual blood in
      3D volume-selective vessel wall imaging.

PMID- 16456825
TI  - Improved temporal clustering analysis method for detecting multiple response
      peaks in fMRI.
AB  - PURPOSE: To develop an improved temporal clustering analysis (TCA) method for
      detecting multiple active peaks by running the method once. MATERIALS AND
      METHODS: Two cases of simulation data and a set of actual fMRI data from nine
      subjects were used to compare the traditional TCA method with the new method,
      termed extremum TCA (ETCA). The first case of simulation data simulated event
      related activation and block activation in one cerebral area, and the second case
      simulated event-related activation and block activation in two cerebral areas. An
      in vivo visual stimulating experiment was performed on a 1.5T MR scanner. All
      imaging data were processed using both traditional TCA and the new method.
      RESULTS: The results of both the simulated and actual fMRI data show that the new
      method is more sensitive and exact than traditional TCA in detecting multiple
      response peaks. CONCLUSION: The new method is effective in detecting multiple
      activations even when the timing and location of the brain activation are
      completely unknown.

PMID- 16456826
TI  - Adult-onset primary lower limb dystonia.
AB  - The lower extremity is affected infrequently in adult-onset primary dystonia in
      contrast to childhood-onset dystonia, which typically begins in the foot. When
      dystonia affects the foot in an adult, it is usually on a secondary basis. We
      present findings on 17 patients (11 women, 6 men; average age of onset 48.4
      years; average time to diagnosis 2.7 years) with adult-onset primary foot
      dystonia. Prior to diagnosis, most patients underwent extensive testing and
      treatment, including unnecessary surgeries. Only the left lower extremity was
      involved in 8 patients, only the right in 7, and both in 2. The most common
      patterns were plantar flexion of all toes and inversion of the foot, typically
      activated with standing or walking. Only 2 patients had dystonia elsewhere. There
      was a family history of possible dystonia in 2 patients. One of five tested for
      DYT1 was positive, in the absence of a family history. One of eight patients
      treated with levodopa experienced mild improvement. Six of eight treated with
      botulinum toxin improved. No patient has been observed to have a secondary cause
      of dystonia. The prognosis, with regard to progression or spread to other body
      parts, has been favorable. Although uncommon, foot dystonia on a primary basis,
      not due to DYT1, can begin in adulthood. In this series of patients, the
      diagnosis was often not recognized, leading to extensive and unnecessary testing
      and treatment and emphasizing the need for wider recognition.

PMID- 16456827
TI  - The role of M. popliteus in unpredictable and in self-initiated balance
      provocations.
AB  - The purpose of this study was to determine whether m. popliteus (POP) activity
      would contribute to the control of knee joint position in unpredictable and in
      self-initiated provocations of standing balance. Ten healthy women (age 25.2 +/-
      4.5 years, means and SD) without known knee pathology were tested for postural
      reactions (1) to unpredictable support surface translations in anterior and
      posterior directions, and (2) in self-initiated balance provocations in a
      reaction time (RT) forward reach-and-grip task. Electromyographic activity was
      recorded from POP and other leg muscles plus the deltoid muscle. Three
      dimensional kinematics were captured for the knee joint and the body centre of
      mass was calculated. POP was active first of all the muscles recorded, regardless
      of translation direction, and knee joint movements elicited were either knee
      extension or external rotation of the tibia. In the RT task, the POP was active
      after initiation of reaching movement, and there was little consistency in the
      kinematic response. POP activity was not direction specific in response to
      support surface translation, but appeared triggered from reactive knee joint
      movement. The response to the support-surface translation suggests that POP
      served to control knee joint position rather than posture. In the RT task, we
      could not deduce whether POP activity was attributed to knee joint control or to
      postural control.

PMID- 16456828
TI  - Nonweight-bearing anterior knee laxity is related to anterior tibial translation
      during transition from nonweight bearing to weight bearing.
AB  - We examined the relationship between anterior knee laxity (AKL), evaluated while
      the knee was nonweight bearing, and anterior translation of the tibia relative to
      the femur (ATT), evaluated when the knee transitioned from nonweight-bearing to
      weight-bearing conditions in response to an applied compressive load at the foot.
      Twenty subjects with normal knees (10 M, 10 F; 25.2 +/- 4.1 years, 169.8 +/- 11.5
      cm, 71.6 +/- 16.9 kg) underwent measurements of AKL and ATT of the right knee on
      2 days. AKL was measured at 133N with the KT-2000. ATT was measured with the
      Vermont Knee Laxity Device and electromagnetic position sensors attached to the
      patella and the anteromedial aspect of the proximal tibia. Three trials for each
      measure were averaged and analyzed. Measurement consistency was high for both AKL
      (ICC = 0.97; SEM = 0.44 mm) and ATT (ICC = 0.88; SEM = 0.84 mm). Linear
      regression revealed that AKL predicted 35.5% of the variance in ATT (p = 0.006),
      with a prediction equation of Y(ATT) = 3.20 + 0.543(X(AKL)). Our findings suggest
      that increased AKL is associated with increased ATT as the knee transitions from
      nonweight-bearing to weight-bearing conditions. The potential for increased knee
      joint laxity to disrupt normal knee biomechanics during activities such as
      landing from a jump, or the foot strike phase of gait deserves further study.

PMID- 16456829
TI  - Characteristics of the rat supraspinatus tendon during tendon-to-bone healing
      after acute injury.
AB  - Rotator cuff repair is known to have a high failure rate. Little is known about
      the natural healing process of the rotator cuff repair site, hence little can be
      done to improve the tendon's ability to heal. The purpose of this study was to
      investigate the collagen formation at the early repair site and to localize
      TGFbeta-1 and 3 during early healing and compare their levels to cell
      proliferation and histological changes. Bilateral supraspinatus tendons were
      transected and repaired in 60 rats. Specimens were harvested and evaluated at 0,
      1, 3, 7, 10, 28, and 56 days. Histological sections were evaluated for cell
      morphology. Immunohistochemistry and in situ hybridization was performed to
      localize protein and mRNA for collagen types I and III and TGFbeta-1 and 3.
      Proliferating cell nuclear antigen (PCNA) assay was performed to measure cell
      proliferation, and cells were counted to determine cell density. Biomechanical
      properties were evaluated. Repair tissue demonstrated an initial inflammatory
      response with multinucleated cells present at 1 and 3 days, and lymphocytes and
      plasma cells presents at 7 and 10 days. Capillary proliferation began at 3 days
      and peaked at 10 days. Ultimate force increased significantly over the time
      period studied. Collagen I protein and mRNA significantly increased at 10 days,
      and reached a plateau by 28 and 56 days. Collagen III showed a similar trend,
      with an early increase, and remained high until 56 days. TGFbeta-1 was localized
      to the forming scar tissue and showed a distinct peak at 10 days. TGFbeta-3 was
      not seen at the healing insertion site. Cell proliferation and density followed
      the same trend as TGFbeta-1. A wound healing response does occur at the healing
      rotator cuff insertion site, however, the characteristics of the tendon after
      healing differ significantly from the uninjured tendon insertion site at the
      longest time-point studied. A distinctive collagen remodeling process occurred
      with an initial increase in the formation of collagen types I and III followed by
      a decrease toward baseline levels seen at time 0. Growth factor TGFbeta-1 was
      localized to repair tissue and coincided with a peak in cell proliferation and
      cellularity. Repair sites remained unorganized histologically and biomechanically
      inferior in comparison to previously described uninjured insertion sites.

PMID- 16456830
TI  - A new side effect of immunosuppression: high incidence of hearing impairment
      after liver transplantation.
AB  - Little is known about hearing impairment in patients after organ transplantation.
      We conducted a single-center study to evaluate hearing impairment in patients
      after orthotopic liver transplantation (OLT). A questionnaire was sent to 695
      adult patients after OLT to assess characteristics and course of auditory
      impairment. Risk factors such as ototoxic drugs were taken into consideration.
      Clinical follow-up, including immunosuppressive therapy, was analyzed in detail.
      The questionnaire was completed by 521 patients (75%). Hearing impairment was
      reported by 184 patients (35%). A total of 43 patients (8%) suffered from hearing
      abnormalities prior to OLT. The remaining 141 patients (27%) developed hearing
      impairment after transplantation. Main problems were hearing loss (52%), tinnitus
      (38%), and otalgia (30%). There was no association of post-OLT hearing disorders
      with age or known risk factors. In 43% of patients, onset of hearing impairment
      was within 2 yr post-OLT. Hearing loss was positively associated with tacrolimus
      immunosuppression in univariate (P < 0.05) and multivariate analysis (P < 0.02).
      Patients using a hearing aid received tacrolimus more frequently than
      cyclosporine (P < 0.05). In conclusion, subjective hearing impairment is frequent
      in patients after OLT and contributes to post-OLT morbidity. Calcineurin
      inhibitor-related neurotoxicity appears as a possible mechanism. Further
      prospective investigations with objective hearing tests are necessary to confirm
      these results and to evaluate the role of immunosuppression.

PMID- 16456831
TI  - A novel three-dose regimen of daclizumab in liver transplant recipients with
      hepatitis C: a pharmacokinetic and pharmacodynamic study.
AB  - This study evaluated the pharmacokinetics and pharmacodynamics of a novel 3-dose
      regimen of daclizumab in de novo hepatitis C liver transplant recipients. In 30
      of 156 recipients receiving daclizumab, mycophenolate mofetil, tacrolimus, and no
      steroids (Arm 3 of Hep C 3 Liver Study), daclizumab (2, 2, and 1 mg/kg,
      respectively) was given on days 1, 3, and 8 posttransplant, respectively, with
      trough, peak (C(max)), and CD25 saturation (CD(sat)) measured sequentially. Mean
      daclizumab C(max) was 50.3 microg/mL on day 1, and mean trough levels were 21.8,
      25.7, and 9.9 microg/mL on days 3, 8, and 30, respectively. A significant decline
      in CD(sat) (mean, 15.7% to 4.7%) was observed on day 1 and was sustained
      throughout the study (2.8% on day 30). Daclizumab concentration > or = 5
      microg/mL was the level where most of the effect on CD(sat) was noticed. Elevated
      baseline CD(sat) was observed in African Americans, patients weighing < or = 75
      kg, and patients <60 years of age. After 365 days, 2 patients had experienced 3
      rejections, 10 patients had recurrent hepatitis C, 4 patients died, and 2 grafts
      were lost. In conclusion, this novel 3-dose regimen is effective in rapidly
      achieving high therapeutic concentration of daclizumab and a significant decline
      in CD(sat) lasting over 30 days.

PMID- 16456832
TI  - Microscopy of the Drosophila facet eye: vademecum for standardized fixation,
      embedding, and sectioning.
AB  - We describe here a standardized method for histological processing of the
      Drosophila compound eye. Primary fixation with 2.5% glutaraldehyde, obligatorily
      supplemented with 0.1% household detergent regularly yielded the best structural
      preservation, as compared with that of other, more complicated fixation protocols
      tested. Notably, it proved indispensable not only to cut off the fly's head to
      facilitate the penetration of the reagents but also to open the chitinous head
      capsule. For this, we locally pierced the cuticle between the eyes, leaving the
      head structurally almost intact, a prerequisite for precisely aligning the head
      for microtomy. We developed a two-step re-embedding procedure allowing for exact
      and reproducible orientation of the fly heads. Thus, highly comparable series of
      cross sections through a representative number of ommatidia were obtained. The
      feasibility of our embedding and sectioning approach is finally demonstrated by
      three-dimensional reconstructions of the middle segments of the R1, R7, and R8
      photoreceptor cells. We present reconstructions from structurally modified
      ommatidia, as seen after RNAi-mediated depletion of the endosomal adaptor protein
      p14, and from normal ommatidia corresponding to the wildtype.

PMID- 16456833
TI  - Morphogenesis of the different types of photoreceptors of the chicken (Gallus
      domesticus) retina and the effect of amblyopia in neonatal chicken.
AB  - Despite the great variety in chicken photoreceptors, existing morphogenetic
      studies only deal with two types: rods and cones. We have therefore examined by
      scanning electron microscopy the first appearance and maturation of different
      retinal photoreceptors in 36 chicken embryos (Gallus domesticus), aged 5-19 days
      prehatching. On day 5 of incubation, chicken retinae were only composed of
      proliferating ventricular cells devoid of photoreceptors. On day 8, outer mitotic
      cells were separated from inner differentiating photoreceptors, by the transient
      layer of Chievitz. Ball-like protrusions appeared at the ventricular surface,
      representing the first signs of photoreceptor inner segment formation. From day
      10 onward, double cones, single cones, and rods could be clearly distinguished,
      and occasional cilia were detected at their tip. On day 12, inner segments had
      increased in length and diameter, and frequently carried a cilium representing
      the beginning of outer segment formation. On day 14, most photoreceptors
      displayed a distinct outer segment. On day 19, photoreceptors had essentially
      assumed adult morphology. Based on the shape of their outer segments, two
      subtypes of cones and three subtypes of double cones could be distinguished.
      Throughout development, we observed microvilli close to maturing photoreceptors,
      either originating from their lateral sides, from their tip, or from Muller
      cells. Microvillus density peaked between day 12 and 14, indicating an important
      role in photoreceptor morphogenesis. Unilateral occlusion of the eyes of
      posthatching chicken reduced the proportion of double cones to single cones in
      the retina, indicating dependence of retinal morphogenesis upon functional
      activity of visual cells.

PMID- 16456834
TI  - Effects of veratrine on skeletal muscle mitochondria: ultrastructural,
      cytochemical, and morphometrical studies.
AB  - The alkaloid veratrine is a lipid-soluble neurotoxin, which target voltage-gated
      Na+ channels for their primary action. Recently, we showed that this alkaloid may
      cause myonecrosis and evidences suggest mitochondria as one of its cell targets.
      Herein, we investigate the effects caused by variable concentration of veratrine
      (250 and 550 microg/mL) on mitochondrial oxygen consumption, respiratory chain
      enzymes activities, and ultrastructure, combining electron microscopy with
      cytochemical and biochemical approaches. The results showed different sort of
      ultrastructural changes, both in isolated and intramuscular mitochondria.
      Veratrine decreased mitochondrial nicotinamide adenine dinucleotide dehydrogenase
      (NADH-d), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) activities,
      significantly and dose-dependently inhibited the state 3 respiration rate,
      respiratory control ratio (RCR), and ADP/O on isolated rat skeletal muscle
      mitochondria, whereas state 4 was unaffected. A tendency of increase in
      mitochondria diameter was seen with 250 microg/mL veratrine. We conclude that the
      alkaloid would probably act on mitochondrial membrane phospholipid configuration,
      which would explain the changes observed.

PMID- 16456835
TI  - Bordetella adenylate cyclase toxin induces a cascade of morphological changes of
      sheep erythrocytes and localizes into clusters in erythrocyte membranes.
AB  - Adenylate cyclase toxin (CyaA) of Bordetella pertussis penetrates the membrane of
      eukaryotic cells, producing high levels of intracellular cAMP, as well as
      hemolysis that results from the formation of cation-selective toxin channels in
      the membrane. Using several microscopical approaches we studied the effects of
      CyaA action on the morphology of sheep erythrocytes during early phases preceding
      lysis and examined localization of CyaA molecules within the erythrocyte
      membrane. CyaA induced a cascade of morphological changes of erythrocytes, such
      as shrinkage, formation of membrane projections, and blebs and swelling. The use
      of an enzymatically inactive CyaA-AC- toxoid that is unable to produce cAMP and
      of a CyaA-E581K mutant exhibiting higher hemolytic activity than with CyaA showed
      that the hemolytic activity is responsible for the induction of morphological
      changes of erythrocytes. Further, immunolabeling of inserted CyaA-232/FLAG
      molecules with specific anti-FLAG antibodies and IgG-gold particles indicated a
      clustered distribution of CyaA molecules in erythrocyte membrane. This was
      confirmed by immunofluorescence and confocal microscopy, which revealed uniform
      stoichiometry of CyaA clusters, suggesting CyaA binding into specific domains in
      erythrocyte membrane. Indeed, a decrease of CyaA binding after cholesterol
      depletion of erythrocytes suggests toxin targeting and binding to membrane
      microdomains (rafts).

PMID- 16456836
TI  - Distribution of neurotrophin and TrK receptor-like immunoreactivity in the
      adrenal gland of birds.
AB  - The occurrence and localization of neurotrophins and their specific TrK receptor
      like proteins in the adrenal gland of chicken, duck and ostrich were examined by
      immunohistochemical methods. In all species studied NGF-, TrK A- and TrK C-like
      immunoreactivity was observed in neurons and fibers of adrenal ganglia. Thin TrK
      A- and TrK C-like immunoreactive fibers were also observed among chromaffin
      cells. NT-3-like immunoreactivity was detected in chromaffin cells as revealed by
      the double immunolabelings NT-3/chromogranin A and NT-3/DbetaH. The interrenal
      tissue never showed IR to any neurotrophins and TrK tested, and none of the
      adrenal structures displayed immunoreactivity to BDNF and TrK B. Double
      immunolabelings NGF/TrK A, NGF/TrK C and TrK A/TrK C showed colocalization in
      some neurons and fibers in adrenal ganglia. In adrenal glands of the species
      studied, the distribution of neurotrophins and TrK receptors could suggest an
      involvement of NT-3 on neuronal populations innervating adrenal ganglia by means
      of its high affinity receptor TrK C and low affinity receptor TrK A. In addition,
      NGF could be utilized by neuronal populations of adrenal ganglia through its
      preferential receptor TrK A by an autocrine or paracrine modality of action.

PMID- 16456837
TI  - Microscopy under pressure--an optical chamber system for fluorescence microscopic
      analysis of living cells under high hydrostatic pressure.
AB  - High hydrostatic pressure (HHP) becomes more and more interesting for life
      science research, since it can be employed to inactivate various cells. To
      directly monitor "cells under pressure," the development of an optical high
      pressure chamber is required. Therefore, an optical pressure chamber that can be
      used for up to 300 MPa was constructed. This chamber has already been described
      as a tool for in situ observation of dynamic changes of microscopic structures in
      bright field as well as phase contrast. In combination with an inverted
      microscope, we obtained brilliant microscopic color pictures with an optical
      resolution more than 0.56 microm. Here, we demonstrate the capabilities of the
      HHP cell, in combination with epifluorescence microscopy. Using a nonadherent
      human B-cell line (Raji, ATCC CCL 86), stained with the fluorescent dyes
      propidium iodide, Hoechst 33342, or dihexyloxacarbocyanine iodide, we were able
      to show that the system is suitable to perform fluorescence microscopic analyses,
      with pressures up to 300 MPa, with viable mammalian cells.

PMID- 16456838
TI  - Histochemical evidence of osteoclastic degradation of extracellular matrix in
      osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells.
AB  - The aim of this study was to assess the dynamics of osteoclast migration and the
      degradation of unmineralized extracellular matrix in an osteolytic metastasis by
      examining a well-standardized lung cancer metastasis model of nude mice. SBC-5
      human lung small carcinoma cells were injected into the left cardiac ventricle of
      6-week-old BALB/c nu/nu mice under anesthesia. At 25-30 days after injection, the
      animals were sacrificed and their femora and/or tibiae were removed for
      histochemical analyses. Metastatic lesions were shown to occupy a considerable
      area extending from the metaphyses to the bone marrow region. Tartrate resistant
      acid phosphatase (TRAPase)-positive osteoclasts were found in association with an
      alkaline phosphatase (ALPase)-positive osteoblastic layer lining the bone
      surface, but could also be localized in the ALPase-negative stromal tissues that
      border the tumor nodules. These stromal tissues were markedly positive for
      osteopontin, and contained a significant number of TRAPase-positive osteoclasts
      expressing immunoreactivity for CD44. We thus speculated that, mediating its
      affinity for CD44, osteopontin may serve to facilitate osteoclastic migration
      after their formation associated with ALPase-positive osteoblasts. We next
      examined the localization of cathepsin K and matrix metallo-proteinase-9 (MMP-9)
      in osteoclasts. Osteoclasts adjacent to the bone surfaces were positive for both
      proteins, whereas those in the stromal tissues in the tumor nests showed only MMP
      9 immunoreactivity. Immunoelectron microscopy disclosed the presence of MMP-9 in
      the Golgi apparatus and in vesicular structures at the baso-lateral cytoplasmic
      region of the osteoclasts found in the stromal tissue. MMP-9-positive vesicular
      structures also contained fragmented extracellular materials. Thus, osteoclasts
      appear to either select an optimized function, namely secreting proteolytic
      enzymes from ruffled borders during bone resorption, or recognize the surrounding
      extracellular matrix by mediating osteopontin/CD44 interaction, and internalize
      the extracellular matrices. Microsc.

PMID- 16456839
TI  - New polyurethane-based material for vascular corrosion casting with improved
      physical and imaging characteristics.
AB  - Vascular corrosion casting has been established as a method to reconstruct the
      three-dimensional (3D) structure of blood vessels of organs and tissues. After
      replacing the blood volume with a low viscosity resin, the surrounding tissue is
      removed to replicate the vascular architecture, typically using scanning electron
      microscopy (SEM). To date available casting resins have had significant
      limitations such as lack of viscosity, leading to insufficient perfusion of
      smallest capillaries in organs and tissues of smaller species, interaction with
      surrounding tissue or fragility of resulting casts. We have reported here about a
      new polyurethane-based casting resin (PU4ii) with superior physical and imaging
      characteristics. Low viscosity, timely polymerization, and minimal shrinking of
      PU4ii produces high quality casts, including the finest capillaries. These casts
      are highly elastic while retaining their original structure to facilitate
      postcasting tissue dissection and pruning of casts. SEM images illustrate the
      high reproduction quality, including endothelial cell imprints, features that
      allow one to discern arterial and veinal vessels. For quantitative analysis,
      casts from PU4ii can be imaged using micro-computed tomography to produce digital
      3D reconstructions. The inherent fluorescence of PU4ii is sufficient to reproduce
      casts with or without tissue using confocal microscopy (CM). Because of the
      simplified casting procedure, the high reproducibility and the superior
      reproduction quality, a combination of vascular corrosion casting using PU4ii
      with advanced imaging technologies has great potential to support the description
      of vascular defects and drug effects in disease models using mutant mice.

PMID- 16456840
TI  - Effect of crosslinking on the elasticity of polyelectrolyte multilayer films
      measured by colloidal probe AFM.
AB  - A homemade colloidal probe atomic force microscope was used to perform
      nanoindentation with a spherical probe of 5 microm in diameter, at different
      approach velocities in order to extract the Young's modulus, E0, of poly(L
      lysine)/hyaluronan (PLL/HA) films. This parameter is of prime importance to
      control cellular adhesion. The films were either kept in their native form or
      cross-linked with a mixture of 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide
      (EDC) and N-hydrosulfosuccinimide (sulfo-NHS), where the EDC concentration was
      varied from 1 up to 100 mg mL(-1) (approximately from 5 to 500 mM). A model based
      on Hertz mechanics was used to account for the interactions between film and
      probe. It is shown that the Young's modulus varies with the approach velocity for
      the native (PLL/HA) films, whereas for cross-linked ones, E0 is independent from
      the velocity over the whole range investigated. It is found that for native
      films, E0 takes a value of 3 kPa at low approach velocities, a velocity domain
      that should be relevant in cellular adhesion processes. The Young's modulus
      increases with the EDC concentration used to cross-link the films and levels off
      at a value of about 400 kPa for EDC concentrations exceeding 40 mg mL(-1). Thus,
      it is possible by crosslinking PLL/HA films to control their elastic properties
      with the aim to alter their behavior as to the cellular adhesion.

PMID- 16456841
TI  - Prenatal diagnosis of persistent left superior vena cava and its associated
      congenital anomalies.
AB  - OBJECTIVE: To evaluate the associated conditions and the outcome of persistent
      left superior vena cava (PLSVC) detected in fetal life. METHODS: This was a
      retrospective review of all cases of PLSVC detected prenatally between 1998 and
      2004 in two tertiary referral centers in Germany. Patient charts, ultrasound
      video recordings and still frames of all cases were reviewed for associated
      conditions and outcome. RESULTS: Eighty-two cases of PLSVC were detected in the
      study period. Thirty-seven cases (45%) were associated with heterotaxy syndromes,
      19 (23%) with isolated cardiac malformations, seven (9%) with aneuploidy, six
      (7%) with complex malformation syndromes and six (7%) with isolated extracardiac
      malformations. Seven cases (9%) had no associated condition. Eighty-three percent
      of the fetuses in this series had associated cardiac malformations; the most
      frequent cardiac malformations in those with heterotaxy syndromes were complete
      atrioventricular septal defect (75%) and right outflow tract obstruction (58%).
      After exclusion of cases with heterotaxy, most congenital heart defects were
      ventricular septal defects (41%) and coarctation (34%). The outcome of PLSVC was
      determined solely by the associated conditions. After exclusion of terminated
      cases, heterotaxy syndromes as well as complete atrioventricular septal defects
      were associated significantly with perinatal and infant death. In contrast, all
      cases with isolated PLSVC or associated correctable extracardiac malformations
      survived and were doing well at the time of writing. CONCLUSIONS: PLSVC detected
      in fetal life has to be followed by a meticulous inspection of the fetal anatomy
      as it is frequently associated with heterotaxy syndromes, other cardiac/non
      cardiac malformations and aneuploidy that determine the outcome. Isolated PLSVC
      is a benign vascular anomaly and may not affect the outcome.

PMID- 16456842
TI  - Prenatal detection of heart defects in a non-selected population of 30,149
      fetuses--detection rates and outcome.
AB  - OBJECTIVES: To evaluate the detection rate of congenital heart defects (CHD) in a
      non-selected population and to follow outcome after diagnosis. METHODS: All
      30,149 fetuses/newborns that were scheduled to deliver at our hospital between
      February 1991 and December 2001 were registered prospectively. Of these, 29,460
      (98%) fetuses had a prenatal ultrasound scan at our center. The routine fetal
      examination at approximately 18 weeks' gestation included the four-chamber view
      and the great arteries of the fetal heart. The follow-up period was 2-13 years.
      RESULTS: Of 97 major CHDs, 55 (57%) were detected prenatally, 16% (9/55) prior
      to, 66% (36/55) at and 18% (10/55) after the routine scan. Forty-four percent
      (19/43) of the isolated CHDs, 67% (36/54) of those with associated malformations
      and 48% (11/23) of the isolated ductal-dependent CHDs were detected. Thirty-eight
      percent (37/97) had an abnormal karyotype. Of the 55 major CHDs detected, 44%
      (24) of the pregnancies with lethal/serious fetal malformations were terminated,
      15% (8) died in utero, 42% (23) were born alive and 27% (15) were still alive
      after 2 years. Of the 42 CHDs detected postnatally, 2% (1) were terminated for
      other reasons, 98% (41) were born alive and 81% (34) were still alive after 2
      years. CONCLUSIONS: Prenatal detection of CHD is still a challenge, with a 57%
      detection rate only. Isolated defects are detected less frequently. The overall
      outcome suggests that the most severe defects are detected with the present
      screening setting; only 27% of the babies with major CHDs detected were still
      alive after 2 years. Data from long-term follow-up will be of importance for the
      counseling process.

PMID- 16456844
TI  - Subacute sclerosing panencephalitis: relationship between clinical stage and
      diffusion-weighted imaging findings.
AB  - PURPOSE: To investigate the relationship between clinical stages and apparent
      diffusion coefficient (ADC) changes in the brain of patients with subacute
      sclerosing panencephalitis (SSPE). MATERIALS AND METHODS: A total of 18 patients
      with stage II (N = 11) and III (N = 7) SSPE and 11 age-matched controls underwent
      routine MRI and diffusion-weighted imaging (DWI). The ADC values were
      automatically calculated. Seven distinct neuroanatomic structures (frontal,
      parieto-occipital, and cerebellar white matter; deep white matter; thalamus;
      basal ganglia; and brainstem) were selected for analysis in the patient and
      control groups. RESULTS: Hyperintensities in the periventricular and subcortical
      white matters on T2-weighted images and ADC maps were detected in 63.6% of
      patients with stage II and in all patients with stage III. There were significant
      differences between stage II and III patients and also between patients and
      control group in ADC values that obtained from all locations. The highest mean
      ADC values were calculated in stage III patients. Although MRI and DWI findings
      were normal in four patients with stage II disease, ADC values were significantly
      increased when compared with controls. CONCLUSION: The stage of disorder may be
      independent of DWI appearance during the early stage (stages I and II), even
      though the brain is affected. Therefore, DWI and ADC values supplemental to
      routine MRI should also be utilized for lesion detection and definition to
      enhance diagnostic accuracy in patients with SSPE.

PMID- 16456845
TI  - The practical application of a mathematical model to predict the outcome of
      pregnancies of unknown location.
AB  - OBJECTIVE: A logistic regression model has been developed previously to predict
      which pregnancies of unknown location (PULs) become ectopics. This model was
      based on the human chorionic gonadotropin (hCG) ratio (hCG 48 h/hCG 0 h). The aim
      of this study was to evaluate the model in an early pregnancy clinical setting.
      METHODS: This was a prospective non-interventional observational study. Women
      classified as having a PUL had serum hCG and progesterone levels taken at
      presentation and 48 h later. At 48 h, nurse practitioners in the early pregnancy
      unit gave their subjective assessment of the likely pregnancy outcome based upon
      existing strategies to predict the outcome of PULs and their own previous
      experience. This was used as the basis for the clinical management of the women.
      The hormonal data were then entered into the model, which was available on the
      clinic computer in the form of a Microsoft Excel package, and the predicted
      outcome according to this model was recorded for each case. The model was
      weighted in favor of detecting an ectopic pregnancy at the expense of failing
      PULs and intrauterine pregnancies. All women were followed up until the final
      true diagnosis was established: a failing PUL, an intrauterine pregnancy or an
      ectopic pregnancy. The predicted outcome according to the model was compared with
      that of the subjective assessment of the expert operator and the true outcome
      after follow-up. RESULTS: Data were obtained from 357 women classified as having
      PULs. The final clinical outcomes were: 162 (45.4%) failing PULs, 166 (46.5%)
      intrauterine pregnancies and 29 (8.1%) ectopic pregnancies. Subjective assessment
      utilizing current strategies gave sensitivities of 79.3%, 92.8% and 87.0% for the
      detection of ectopic pregnancy, intrauterine pregnancy and failing PUL,
      respectively. The model detected ectopic pregnancy, intrauterine pregnancy and
      failing PUL with sensitivities of 82.8%, 86.8% and 73.5%, respectively. There
      were no adverse outcomes. CONCLUSION: This logistic regression model, based on
      the hCG ratio, can be used to predict the outcome of PULs, especially the ectopic
      pregnancies, with a high degree of certainty. It compares favorably with
      subjective assessment by experienced operators using current strategies to
      predict the outcome of PULs. The model can be used by those with limited
      knowledge or understanding of the behavior of serum biochemistry in the first
      trimester and in turn aid in the classification of PULs into those at low and
      those at high risk of ectopic pregnancy at 48 h.

PMID- 16456846
TI  - In vivo and in vitro analysis of the vasculogenic potential of avian
      proepicardial and epicardial cells.
AB  - Coronary vessel formation is a special case in the context of embryonic vascular
      development. A major part of the coronary cellular precursors (endothelial,
      smooth muscle, and fibroblastic cells) derive from the proepicardium and the
      epicardium in what can be regarded as a late event of angioblastic and smooth
      muscle cell differentiation. Thus, coronary morphogenesis is dependent on the
      epithelial-mesenchymal transformation of the proepicardium and the epicardium. In
      this study, we present several novel observations about the process of coronary
      vasculogenesis in avian embryos, namely: (1) The proepicardium displays a high
      vasculogenic potential, both in vivo (as shown by heterotopic transplants) and in
      vitro, which is modulated by vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor signals; (2) Proepicardial and epicardial cells co
      express receptors for platelet-derived growth factor-BB and VEGF; (3) Coronary
      angioblasts (found all through the epicardial, subepicardial, and compact
      myocardial layers) express the Wilms' tumor associated transcription factor and
      the retinoic acid-synthesizing enzyme retinaldehyde-dehydrogenase-2, two markers
      of the coelomic epithelium involved in coronary endothelium development. All
      these results contribute to the development of our knowledge on the vascular
      potential of proepicardial/epicardial cells, the existent interrelationships
      between the differentiating coronary cell lineages, and the molecular mechanisms
      involved in the regulation of coronary morphogenesis.

PMID- 16456847
TI  - Two-stage support vector regression approach for predicting accessible surface
      areas of amino acids.
AB  - We address the problem of predicting solvent accessible surface area (ASA) of
      amino acid residues in protein sequences, without classifying them into buried
      and exposed types. A two-stage support vector regression (SVR) approach is
      proposed to predict real values of ASA from the position-specific scoring
      matrices generated from PSI-BLAST profiles. By adding SVR as the second stage to
      capture the influences on the ASA value of a residue by those of its neighbors,
      the two-stage SVR approach achieves improvements of mean absolute errors up to
      3.3%, and correlation coefficients of 0.66, 0.68, and 0.67 on the Manesh dataset
      of 215 proteins, the Barton dataset of 502 nonhomologous proteins, and the Carugo
      dataset of 338 proteins, respectively, which are better than the scores published
      earlier on these datasets. A Web server for protein ASA prediction by using a two
      stage SVR method has been developed and is available (http://birc.ntu.edu.sg/~
      pas0186457/asa.html).

PMID- 16456848
TI  - Cytopathologic features of olfactory neuroblastoma.
AB  - BACKGROUND: Olfactory neuroblastoma (ONB) is an uncommon neoplasm arising from
      the olfactory mucosa. Because its cytopathology is largely limited to case
      reports, the goal was to evaluate a series of ONB cases, compare them with
      previously reported cases, and with a control group of pulmonary and cutaneous
      small cell neuroendocrine carcinoma (NEC). METHODS: Six fine-needle aspiration
      (FNA) biopsies of metastatic ONB and one case with imprint smears of primary ONB
      were recovered from files. Aspirates from seven FNA cases of metastatic pulmonary
      small cell NEC and four cases of metastatic Merkel cell carcinoma to the head and
      neck functioned as a control group and were compared with those of ONB. RESULTS:
      Seven cases from 4 patients included 3 males (ages 33-39 yrs) and 1 female (age
      58 yrs). Aspirates were acquired from soft tissues of the neck (three cases),
      cervical lymph nodes (two cases), parietal scalp (one case), and imprint of a
      nasal mass (one case). A correct cytologic diagnosis of metastatic ONB (five
      cases) or malignant small round cell tumor (one case) was made in six cases. One
      aspirate was misdiagnosed as a reactive lymph node. The single primary tumor and
      five of six metastatic tumors were histologically confirmed. Cytologic features
      were similar in all cases. These included high cellularity (seven of seven
      cases), distribution as single forms and cell clusters (seven of seven cases), a
      two-cell population of intact and apoptotic nuclei (seven of seven cases),
      nuclear molding (seven of seven cases), paranuclear 'blue bodies' (five of seven
      cases), necrosis (five of seven cases), and absence of lymphoglandular bodies
      (seven of seven cases). Unlike prior reports, no case exhibited rosettes or
      fibrillar neuropil on smears. All examples from the control group displayed
      nearly identical cytomorphologic features to those of the study group.
      CONCLUSIONS: The cytopathology of metastatic ONB is nonspecific unless fibrillar
      neuropil is identified. Nonetheless, a cytopathologic diagnosis of metastatic ONB
      can be made with confidence in nearly all patients if a well documented history
      of ONB exists. Minus such a clinical context, aspirates of metastatic ONB may be
      mistaken for metastatic pulmonary small cell NEC, cutaneous neuroendocrine
      (Merkel cell) carcinoma, and even small cell lymphoma.

PMID- 16456849
TI  - Neuronal leucine-rich repeat 6 (XlNLRR-6) is required for late lens and retina
      development in Xenopus laevis.
AB  - Leucine-rich repeat proteins expressed in the developing vertebrate nervous
      system comprise a complex, multifamily group, and little is known of their
      developmental function in vivo. We have identified a novel member of this group
      in Xenopus laevis, XlNLRR-6, and through sequence and phylogenetic analysis, have
      placed it within a defined family of vertebrate neuronal leucine-rich repeat
      proteins (NLRR). XlNLRR-6 is expressed in the developing nervous system and
      tissues of the eye beginning at the neural plate stage, and expression continues
      throughout embryonic and larval development. Using antisense morpholino
      oligonucleotide (MO) -mediated knockdown of XlNLRR-6, we demonstrate that this
      protein is critical for development of the lens, retina, and cornea. Reciprocal
      transplantation of presumptive lens ectoderm between MO-treated and untreated
      embryos demonstrate that XlNLRR-6 plays autonomous roles in the development of
      both the lens and retina. These findings represent the first in vivo functional
      analysis of an NLRR family protein and establish a role for this protein during
      late differentiation of tissues in the developing eye.

PMID- 16456850
TI  - Chemometric tools for classification and elucidation of protein secondary
      structure from infrared and circular dichroism spectroscopic measurements.
AB  - Protein classification and characterization often rely on the information
      contained in the protein secondary structure. Protein class assignment is usually
      based on X-ray diffraction measurements, which need the protein in a crystallized
      form, or on NMR spectra, to obtain the structure of a protein in solution. Simple
      spectroscopic techniques, such as circular dichroism (CD) and infrared (IR)
      spectroscopies, are also known to be related to protein secondary structure, but
      they have seldom been used for protein classification. To see the potential of
      CD, IR, and combined CD/IR measurements for protein classification, unsupervised
      pattern recognition methods, Principal Component Analysis (PCA) and cluster
      analysis, are proposed first to check for natural grouping tendencies of proteins
      according to their measured spectra. Partial Least Squares Discriminant Analysis
      (PLS-DA), a supervised pattern recognition method, is used afterwards to test the
      possibility to model explicitly each protein class and to test these models in
      class assignment of unknown proteins. Determination of the protein secondary
      structure, understood as the prediction of the abundance of the different
      secondary structure motifs in the biomolecule, was carried out with the local
      regression method interval Partial Least Squares (iPLS). CD, IR, and CD/IR
      measurements were correlated to the fraction of the motif to be predicted,
      determined from X-ray measurements. iPLS builds models extracting the spectral
      information most correlated to a specific secondary motif and avoids the use of
      irrelevant spectral regions. Spectral intervals chosen by iPLS models provide
      structural information which can be used to confirm previous biochemical
      assignments or identify new motif-related spectral features. The predictive
      ability of the models built with the selected spectral regions has a quality
      similar to previous classical approaches.

PMID- 16456851
TI  - Cardiovascular development: toward biomedical applicability.

PMID- 16456852
TI  - Predicting protease types by hybridizing gene ontology and pseudo amino acid
      composition.
AB  - Proteases play a vitally important role in regulating most physiological
      processes. Different types of proteases perform different functions with
      different biological processes. Therefore, it is highly desired to develop a fast
      and reliable means to identify the types of proteases according to their
      sequences, or even just identify whether they are proteases or nonproteases. The
      avalanche of protein sequences generated in the postgenomic era has made such a
      challenge become even more critical and urgent. By hybridizing the gene ontology
      approach and pseudo amino acid composition approach, a powerful predictor called
      GO-PseAA predictor was introduced to address the problems. To avoid redundancy
      and bias, demonstrations were performed on a dataset where none of proteins has
      >/= 25% sequence identity to any other. The overall success rates thus obtained
      by the jackknife cross-validation test in identifying protease and nonprotease
      was 91.82%, and that in identifying the protease type was 85.49% among the
      following five types: (1) aspartic, (2) cysteine, (3) metallo, (4) serine, and
      (5) threonine. The high jackknife success rates yielded for such a stringent
      dataset indicate the GO-PseAA predictor is very powerful and might become a
      useful tool in bioinformatics and proteomics.

PMID- 16456853
TI  - Follow-up of uteroplacental vascularization after feticide in third-trimester
      therapeutic termination of pregnancy with complete placenta previa.

PMID- 16456854
TI  - Genes, forces, and forms: mechanical aspects of prenatal craniofacial
      development.
AB  - Current knowledge of molecular signaling during craniofacial development is
      advancing rapidly. We know that cells can respond to mechanical stimuli by
      biochemical signaling. Thus, the link between mechanical stimuli and gene
      expression has become a new and important area of the morphological sciences.
      This field of research seems to be a revival of the old approach of developmental
      mechanics, which goes back to the embryologists His (1874), Carey (1920), and
      Blechschmidt (1948). These researchers argued that forces play a fundamental role
      in tissue differentiation and morphogenesis. They understood morphogenesis as a
      closed system with living cells as the active part and biological, chemical, and
      physical laws as the rules. This review reports on linking mechanical aspects of
      developmental biology with the contemporary knowledge of tissue differentiation.
      We focus on the formation of cartilage (in relation to pressure), bone (in
      relation to shearing forces), and muscles (in relation to dilation forces). The
      cascade of molecules may be triggered by forces, which arise during physical cell
      and tissue interaction. Detailed morphological knowledge is mandatory to
      elucidate the exact location and timing of the regions where forces are exerted.
      Because this finding also holds true for the exact timing and location of
      signals, more 3D images of the developmental processes are required. Further
      research is also required to create methods for measuring forces within a tissue.
      The molecules whose presence and indispensability we are investigating appear to
      be mediators rather than creators of form.

PMID- 16456855
TI  - Dlk1 expression marks developing endothelium and sites of branching morphogenesis
      in the mouse embryo and placenta.
AB  - The protein product of the Delta-like 1 (Dlk1) gene belongs to the Delta-Notch
      family of signaling molecules, proteins involved in cell fate determination in
      many tissues during development. The DLK1 protein is believed to function as a
      growth factor, maintaining the proliferative state of undifferentiated cells, and
      is usually down-regulated as immature cells differentiate. The expression pattern
      of the DLK1 protein has been described in certain human tissues; however, Dlk1
      expression is not well understood in the mouse, the most tractable mammalian
      genetic model system. To better understand the role of Dlk1 in embryonic
      development, the tissue-specific expression pattern of Dlk1 mRNA during mouse
      embryogenesis was analyzed by in situ hybridization. In embryonic day 12.5
      (e12.5) embryos, high levels of Dlk1 were found in the developing pituitary,
      pancreas, lung, adrenal, and many mesodermally derived tissues. Strikingly, Dlk1
      expression also marks the growing branches of organs that develop through the
      process of branching morphogenesis. At e16.5, Dlk1 expression is down-regulated
      in most tissues but remains in the pituitary, the adrenal gland, and in skeletal
      muscle. In the placenta, expression of Dlk1 is detected in endothelial cells
      lining the fetal blood vessels of the labyrinth. This pattern is distinct from
      that seen in the human placenta and suggests a role for Dlk1 in regulating
      maternal-fetal interactions.

PMID- 16456856
TI  - Spontaneous splenic rupture in a patient with factor XIII deficiency and a novel
      mutation.
AB  - We report a novel mutation in factor XIIIA gene that caused severe congenital
      factor XIII deficiency in a 6 year and 8 month old male. The mutation is a GA
      deletion in the core domain leading to a premature stop at codon 502. The child
      had severe deficiency with two episodes of intracerebral hemorrhage. He also
      developed spontaneous splenic rupture, an unusual complication of this disorder.

PMID- 16456857
TI  - Outcome for children <4 years of age with malignant central nervous system tumors
      treated with high-dose chemotherapy and autologous stem cell rescue.
AB  - BACKGROUND: Children <4 years of age (yo) with malignant central nervous system
      (CNS) tumors have a dismal prognosis. In an attempt to delay or obviate radiation
      therapy (XRT) and improve outcome, our institution has treated children <4 yo
      with newly diagnosed malignant CNS tumors with high-dose chemotherapy (HDC) and
      autologous stem cell rescue (ASCR) followed by selective XRT. PROCEDURE: Fifteen
      children (age 4-38 months) with malignant CNS tumors have completed treatment
      with HDC/ASCR. All patients received three cycles of induction chemotherapy
      (cisplatin 3.5 mg/kg- day 0, cyclophosphamide 60 mg/kg- day 1 and 2, etoposide
      2.5 mg/kg- day 0-2, vincristine 0.05 mg/kg, day 0, 7, 14) followed by three
      cycles of HDC (carboplatin 17 mg/kg and thiotepa 6 mg/kg, day 0 and 1) with ASCR.
      Histology included five medulloblastomas, four primitive neuroectodermal tumors
      (PNET), five malignant gliomas, and one ependymoma. Outcome and treatment
      toxicities were evaluated by retrospective chart review. RESULTS: Median follow
      up time of the 15 patients is 22 months (range 8-82 months). The 1- and 2-year
      progression-free survival (PFS) is 86.1% and 52.2% and overall survival (OS)
      91.6% and 72.1%, respectively. Ten patients are alive and disease free 3-77
      months (median 18 months) after having completed HDC/ASCR, thereoff five received
      XRT. Toxicity was primarily myelosuppression. There was no treatment mortality.
      CONCLUSIONS: We are encouraged by the outcome of 15 children <4 yo with malignant
      CNS tumors treated with tandem cycles of HDC and ASCR at our institution. The
      treatment regimen is relatively well tolerated.

PMID- 16456858
TI  - Stress lysis in childhood leukemia.
AB  - Children with acute lymphoblastic leukemia (ALL) can experience a decrease in
      their white blood count (WBC) prior to chemotherapy, a phenomenon commonly
      attributed to the administration of allopurinol and hydration. We reviewed the
      records of 20 children with newly diagnosed ALL prior to the administration of
      allopurinol and found that 80% of patients experienced a decrease in their WBC
      (median decrease 14,000/mm(3)) in the less than 24-hr interval between evaluation
      at the referring center and admission to our hospital (P = 0.002). The basis for
      this often-observed phenomenon appears to be that leukemic cells rapidly lyse in
      response to the stress-induced release of endogenous corticosteroids.

PMID- 16456859
TI  - Remission of aplastic anemia induced by treatment for Graves disease in a
      pediatric patient.
AB  - Aplastic anemia (AA) is mediated by T-cell autoimmunity in the majority of cases;
      it is rare and mostly idiopathic in children. We describe a child, who developed
      AA following Graves' disease which could not be attributed to antithyroid drugs.
      We hypothesized that both diseases were caused by similar autoimmune process. We
      monitored the blood counts and did not administer any conventional treatment for
      AA assuming that the existing anti- hematopoietic stem cell humoral and cellular
      immunity might subside with induction of remission of Grave's disease. The child
      went into complete remission with the treatment of the Graves' disease.

PMID- 16456861
TI  - TASSER-based refinement of NMR structures.
AB  - The TASSER structure prediction algorithm is employed to investigate whether NMR
      structures can be moved closer to their corresponding X-ray counterparts by
      automatic refinement procedures. The benchmark protein dataset includes 61
      nonhomologous proteins whose structures have been determined by both NMR and X
      ray experiments. Interestingly, by starting from NMR structures, the majority
      (79%) of TASSER refined models show a structural shift toward their X-ray
      structures. On average, the TASSER refined models have a root-mean-square
      deviation (RMSD) from the X-ray structure of 1.785 A (1.556 A) over the entire
      chain (aligned region), while the average RMSD between NMR and X-ray structures
      (RMSD(NMR_X-ray)) is 2.080 A (1.731 A). For all proteins having a RMSD(NMR_X-ray)
      >2 A, the TASSER refined structures show consistent improvement. However, for the
      34 proteins with a RMSD(NMR_X-ray) <2 A, there are only 21 cases (60%) where the
      TASSER model is closer to the X-ray structure than NMR, which may be due to the
      inherent resolution of TASSER. We also compare the TASSER models with 12 NMR
      models in the RECOORD database that have been recalculated recently by Nederveen
      et al. from original NMR restraints using the newest molecular dynamics tools. In
      8 of 12 cases, TASSER models show a smaller RMSD to X-ray structures; in 3 of 12
      cases, where RMSD(NMR_X-ray) <1 A, RECOORD does better than TASSER. These results
      suggest that TASSER can be a useful tool to improve the quality of NMR
      structures.

PMID- 16456860
TI  - Comment on: "Energy landscape of a small peptide revealed by dihedral angle
      principal component analysis".
AB  - The dihedral angle principal component analysis method published recently by Mu,
      Nguyen, and Stock, is shown to produce distortions of the free energy landscape
      due to the neglect of constraints in the coordinates. It is further shown that
      these distortions can create artificial minima and energy barriers. The rugged
      energy landscape that the authors find for a small peptide chain might thus be an
      artifact of their method.

PMID- 16456862
TI  - Neuregulin regulates the formation of radial glial scaffold in hippocampal
      dentate gyrus of postnatal rats.
AB  - In the rodent hippocampus, the radial glial scaffold consists of radial glial
      cells (RGCs) and plays important roles in neurogenesis in this area after birth.
      However, the mechanisms that maintain the radial glial scaffold in the postnatal
      dentate gyrus (DG) area remain elusive. In the present work, we studied the role
      of Neuregulin (NRG) in the formation and maintenance of the radial glial scaffold
      in the hippocampal DG of postnatal rats using slice culture. We found that ErbB4
      receptors were expressed in vimentin-positive RGCs in DG of postnatal day 6 (P6)
      rats. Treatment with NRG and Ab-3, the inhibitor of ErbB4, revealed that in P6
      rats exogenous NRG promoted the proliferation of Vimentin-positive RGCs in DG. On
      the other hand, endogenous NRG was found necessary for maintaining the
      characteristic morphological and immunohistochemical features of these cells.
      These results indicated that NRG plays a critical role in the formation and
      maintenance of the radial glial scaffold in the hippocampal DG of postnatal rats.

PMID- 16456863
TI  - An open trial of paroxetine for the "offensive subtype" of taijin kyofusho and
      social anxiety disorder.
AB  - The taijin kyofusho (TKS) offensive subtype is thought to be a culture-bound
      syndrome similar to social anxiety disorder (SAD). In Western countries, such
      patients would be diagnosed as having delusional disorder, somatic subtype, or
      body dysmorphic disorder. Recently, open trials for the TKS offensive subtype and
      a randomized controlled trial for body dysmorphic disorder demonstrated that
      selective serotonin reuptake inhibitors (SSRIs) might be as effective in TKS as
      in SAD. This study investigated the efficacy of the SSRI paroxetine in patients
      with the TKS offensive subtype, both on anxiety and fears, as well as insight.
      This study was a 12-week open trial using paroxetine in 22 patients with TKS.
      Subjects were diagnosed based on the original diagnostic criteria for the TKS
      offensive subtype. Insight regarding TKS symptoms was assessed by the 11th
      supplement subscale "Insight into obsessions and compulsions" of the Yale-Brown
      Obsessive Compulsive Scale (Y-BOCS). The Liebowitz Social Anxiety Scale (LSAS),
      the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI),
      Rosenberg's Self-Esteem Scale, and the Interpersonal Distrust subscale of the
      Eating Disorder Inventory were also administered. Offensive anxiety was assessed
      by the original TKS offensive anxiety subscale (0-3 points). The primary efficacy
      variable was the Clinical Global Impression scale (CGI) global improvement item.
      Nineteen patients completed the study. Forty-seven percent (9/19) were responders
      to the drug treatment (scoring 2 or less on the CGI). Last observation carried
      forward (LOCF) analysis (N=22) demonstrated a statistically significant reduction
      in LSAS total score and offensive anxiety in TKS, and the insight scale score of
      the Y-BOCS also significantly improved. Interpersonal distrust showed a trend
      toward improvement.

PMID- 16456864
TI  - In vivo serial diffusion tensor imaging of experimental spinal cord injury.
AB  - In vivo longitudinal diffusion tensor imaging (DTI) of rodent spinal cord injury
      (SCI) was carried out over a period of eight weeks post-injury. A balanced,
      rotationally invariant, alternating gradient polarity icosahedral diffusion
      encoding scheme was used for an unbiased estimation of the DTI metrics. The
      fractional anisotropy (FA), diffusivities along (longitudinal), and perpendicular
      (transverse) to the fiber tracts, were estimated for the ventral, dorsal, and
      lateral white matter. In all the three regions, the DTI metrics were observed to
      be significantly different in injured cords relative to the uninjured controls
      close to the epicenter of the injury. However, these differences gradually
      disappeared away from the epicenter. The spatio-temporal changes in the DTI
      metrics showed a recovery pattern that is region specific. Although the temporal
      trends in the tissue recovery in rostral and caudal sections seem to be similar,
      overall the DTI metrics were observed to be closer to the normal tissue values in
      the caudal relative to the rostral sections (rostral-caudal asymmetry).

PMID- 16456865
TI  - Detection of circulating endothelial cells and endothelial progenitor cells by
      flow cytometry.

PMID- 16456866
TI  - Flow cytometric measurement of circulating endothelial cells: the effect of age
      and peripheral arterial disease on baseline levels of mature and progenitor
      populations.
AB  - BACKGROUND: Age and cardiovascular disease status appear to alter numbers and
      function of circulating endothelial progenitor cells (EPCs). Despite no universal
      phenotypic definition, numerous studies have implicated progenitors with apparent
      endothelial potential in local responses to vascular injury and with
      cardiovascular disease in general. To further define the role of this lineage in
      peripheral artery disease (PAD), we developed a multiparameter flow cytometry
      assay to analyze multiple phenotypic definitions of progenitor cells (PCs), EPCs,
      and mature endothelial cells (ECs) and evaluate effects of age and PAD on
      baseline levels of each subset. METHODS: Blood was collected from young healthy
      subjects (N = 9, mean age 33 +/- 8 years), older healthy subjects (N = 13, mean
      age 66 +/- 8 years), and older subjects with PAD (N = 15, mean age 69 +/- 8
      years). After ammonium chloride lysis, cells were stained and analyzed on a
      Becton-Dickinson LSR II with a 5-color antibody panel: FITC-anti-CD31, PE-anti
      CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33 (lineage panel), PE-Cy7
      anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide
      exclusion, and only viable, low to medium side scatter lineage-negative singlets
      were analyzed. In some studies, cells were sorted for morphological studies.
      Subsets were defined as indicated later. RESULTS: Our results, using a
      comprehensive flow cytometric panel, indicate that CD133+, CD34+, and
      CD133+/CD34+ PCs are elevated in younger healthy individuals compared to older
      individuals, both healthy and with PAD. However, the number of EPCs and mature
      ECs did not significantly differ among the three groups. Assessment of
      endothelial colony forming units and dual acLDL-lectin staining supported the
      flow cytometric findings. CONCLUSIONS: We describe a comprehensive flow
      cytometric method to detect circulating mature and progenitor endothelial
      populations confirmed by conventional morphological and functional assays. Our
      findings suggest that aging may influence circulating levels of PCs, but not EPCs
      or ECs; PAD had no effect on baseline levels of any populations investigated.
      This study provides the basis for evaluating the potential effects of acute
      stress and therapeutic intervention on circulating progenitor and endothelial
      populations as a biomarker for cardiovascular status.

PMID- 16456868
TI  - A simple correction for cell autofluorescence for multiparameter cell-based
      analysis of human solid tumors.
AB  - BACKGROUND: Corrections that have been proposed to minimize the unwanted
      contribution of cell autofluorescence to the total fluorescence signal often
      require either specialized instrumentation or the sacrifice of a data channel so
      as to perform a measurement that can be used to correct for autofluorescence in
      individual cells. Here we propose a simple cell by cell correction for
      autofluorescence that is suitable for multiparameter laser scanning cytometry
      (LSC) studies in human solid tumors that relies on the ratio of mean
      autofluorescence to mean total cell fluorescence (mean Flauto/mean Fltotal). This
      approach assumes a correlation between the autofluorescence component and the
      total signal in individual cells. This correction does not require specialized
      instrumentation, and does not sacrifice a data channel in multiparameter studies.
      A potential disadvantage is that errors may be introduced by the assumption of a
      correlation between the two components of the total fluorescence signal in
      individual cells in samples in which no such correlation exists. METHODS:
      Distributions of cell autofluorescence and total Her-2/neu cell fluorescence were
      obtained separately by LSC in three human breast cancer cell lines and in three
      samples of primary human lung cancer. In the breast cancer cell lines,
      autofluorescence measurements and Her-2/neu measurements were also obtained on
      the same cells. RESULTS: We show that there is a partial correlation between
      autofluorescence and total Her-2/neu/FITC fluorescence in individual cells in the
      three breast cancer cell lines. We also show that the results of a ratio-based
      autofluorescence correction agree with those based on a true cell by cell
      correction. Computer simulation studies suggest that in samples with no
      correlation between the autofluorescence component and the true probe/dye
      fluorescence component, the ratio correction produces robust estimates of the
      mean true fluorescence signal, with relatively small but systematic
      underestimates of the coefficient of variation of such measurements under
      conditions commonly encountered in the measurement of human solid tumors.
      CONCLUSIONS: A simple cell by cell correction for autofluorescence based on the
      ratio of mean Flauto to mean Fltotal can be applied in cell samples in which
      there is a correlation between cell autofluorescence and true probe/dye
      fluorescence in individual cells. In cell samples that lack this correlation, or
      in which it is not known whether such a correlation exists, this correction can
      be used with the reservation that there is a systematic but relatively small
      underestimation of the degree of variability of the measurements.

PMID- 16456867
TI  - Comparison between pimonidazole binding, oxygen electrode measurements, and
      expression of endogenous hypoxia markers in cancer of the uterine cervix.
AB  - BACKGROUND: Although tumor hypoxia has been associated with a more aggressive
      phenotype and lower cure rate, there is no consensus as to the method best suited
      for routine measurement. Binding of the chemical hypoxia marker, pimonidazole,
      and expression of the endogenous hypoxia markers HIF-1alpha and CAIX were
      compared for their ability to detect hypoxia in tumor biopsies from 67 patients
      with advanced carcinoma of the cervix. METHODS: Two biopsies were taken one day
      after administration of pimonidazole and were analyzed for pimonidazole binding
      using flow cytometry or immunohistochemistry. CAIX and HIF-1alpha expression and
      degree of colocalization were measured in sequential antibody-stained sections.
      Patient subsets were examined for tumor oxygen tension using an Eppendorf
      electrode, S phase DNA content, or change in HIF-1alpha expression over the
      course of treatment. RESULTS: Approximately 6% of the tumor area stained positive
      for pimonidazole, HIF-1alpha, or CAIX. The CAIX positive fraction correlated with
      the pimonidazole positive fraction (r = 0.60). Weaker but significant
      correlations were observed between pimonidazole and HIF-1alpha (r = 0.31) and
      CAIX and HIF-1alpha (r = 0.41). Taking the extent of marker colocalization into
      consideration increased the confidence that all markers were identifying hypoxic
      regions. Over 65% of stained areas showed a high degree of colocalization with
      the other markers. Oxygen microelectrode measurements and S phase fraction were
      not correlated with the hypoxic fraction measured using the three hypoxia
      markers. HIF-1alpha levels tended to decrease with time after the start of
      therapy. CONCLUSIONS: Endogenous hypoxia marker binding shows reasonable
      agreement, in extent and location, with binding of pimonidazole. CAIX staining
      pattern is a better match to the pimonidazole staining pattern than is HIF
      1alpha, and high CAIX expression in the absence (or low levels) of HIF-1alpha may
      indicate a different biology.

PMID- 16456871
TI  - Axon-like processes in type III cells of taste organs.
AB  - Type III cells of the taste organs are widely considered to be chemoreceptors.
      The present study was performed on the frog taste disk and describes an axon-like
      process in type III cells, which often contains a bundle of densely-packed
      parallel microfilaments. These processes pass through the basal membrane of the
      gustatory epithelium, running into the lamina propria (transbasal membrane
      processes, tBMPs). In their intraepithelial tract, tBMPs contain dense-cored
      vesicles revealing their origin from type III cells. Type III cells showing both
      classic nonrigid processes (with vesicles and nerve contacts) and tBMPs are
      present. The connective tract of a tBMP usually contains dense-cored vesicles
      only in its proximal portion. In some cases, the connective tract of tBMPs is
      almost perpendicular to the basal lamina. In other cases, it runs parallel to and
      below the basal lamina. Some tBMPs contact nerve fibers running in the
      subepithelial connective tissue; the contact area is rather wide but evident
      synapse-like junctions were never detected. Contacts between tBMPs and nerve
      fibers innervating basal cells are also found. In conclusion, the data
      demonstrate the existence of epithelial cells resembling primitive neurons that
      display an apical dendrite and axon-like basal processes. Until now, it was not
      considered possible that epithelial receptor cells extend processes out of the
      epithelium.

PMID- 16456869
TI  - Quantitative flow cytometry of ZAP-70 levels in chronic lymphocytic leukemia
      using molecules of equivalent soluble fluorochrome.
AB  - BACKGROUND: ZAP-70 has emerged as a potential pivotal prognostic marker for
      patients with chronic lymphocytic leukemia (CLL), which could replace
      immunoglobulin heavy chain mutation status. Although several flow cytometry
      assays have been described for assessing ZAP-70 in CLL, certain technical and
      scientific issues remain unsolved, which have prevented results of this crucial
      test from being reported, even in the best routine flow cytometry laboratories.
      In this report, we aimed to solve some of these issues by providing a
      computerized quantitative flow cytometric assay for ZAP-70 within the entire CLL
      population, which would be easy to perform and enable standardization between
      laboratories. METHODS: Intracellular ZAP-70 levels in CLL and normal B cells were
      assessed by molecules of equivalent soluble fluorochrome (MESF), employing
      Quantum FITC MESF calibration beads to establish a standard curve relating
      channel value to fluorescence intensity in MESF units and the QuickCal v. 2.2
      program (www.bangslabs.com) and clinical relevance of the data was determined.
      RESULTS: The average ZAP-70 expression value in the CD19(+)/CD5(+) cells from 35
      CLL patients was 103,701 MESF when compared with 12,621 MESF in B cells from 20
      normal blood samples. "Low" and "high" ZAP-70 CLL subgroups were defined.
      Patients with "high ZAP-70 MESF" CLL had a shorter time to disease progression (P
      = 0.0005) and a more advanced clinical stage (P = 0.0018) when compared with
      patients in the "low ZAP-70 MESF" CLL subgroup. CONCLUSIONS: This quantitative
      analysis method can be employed to obtain a more specific and highly accurate
      assessment of ZAP-70 levels in CLL cells. The method can easily be standardized,
      in any routine flow laboratory, thereby improving reproducibility and reliability
      of ZAP-70 analysis.

PMID- 16456872
TI  - Evaluation of two 3D virtual computer reconstructions for comparison of cleft lip
      and palate to normal fetal microanatomy.
AB  - Cleft lip and palate reconstructive surgery requires thorough knowledge of normal
      and pathological labial, palatal, and velopharyngeal anatomy. This study compared
      two software algorithms and their 3D virtual anatomical reconstruction because
      exact 3D micromorphological reconstruction may improve learning, reveal spatial
      relationships, and provide data for mathematical modeling. Transverse and frontal
      serial sections of the midface of 18 fetal specimens (11th to 32nd gestational
      week) were used for two manual segmentation approaches. The first manual
      segmentation approach used bitmap images and either Windows-based or Mac-based
      SURFdriver commercial software that allowed manual contour matching, surface
      generation with average slice thickness, 3D triangulation, and real-time
      interactive virtual 3D reconstruction viewing. The second manual segmentation
      approach used tagged image format and platform-independent prototypical SeViSe
      software developed by one of the authors (F.W.). Distended or compressed
      structures were dynamically transformed. Registration was automatic but allowed
      manual correction, such as individual section thickness, surface generation, and
      interactive virtual 3D real-time viewing. SURFdriver permitted intuitive
      segmentation, easy manual offset correction, and the reconstruction showed
      complex spatial relationships in real time. However, frequent software crashes
      and erroneous landmarks appearing "out of the blue," requiring manual correction,
      were tedious. Individual section thickness, defined smoothing, and unlimited
      structure number could not be integrated. The reconstruction remained
      underdimensioned and not sufficiently accurate for this study's reconstruction
      problem. SeViSe permitted unlimited structure number, late addition of extra
      sections, and quantified smoothing and individual slice thickness; however,
      SeViSe required more elaborate work-up compared to SURFdriver, yet detailed and
      exact 3D reconstructions were created.

PMID- 16456873
TI  - Myocardial ischemia tolerance in the newborn rat involving opioid receptors and
      mitochondrial K+ channels.
AB  - Neonatal rat hearts are more tolerant to ischemia compared to adult rat hearts.
      We hypothesized that opioid receptors and mitochondrial potassium channels are
      involved in the elevated ischemia tolerance of neonatal rats. Newborn rats were
      treated by an intraperitoneal injection with sodium chloride (placebo, Pla; n =
      7), naloxone (Nal; n = 8), or K+ (ATP) channel blocker 5-hydroxydecanoate (HD; n
      = 8), or were left untreated (sham; n = 8). Thirty minutes after injection, the
      rats were sacrificed and hearts were arrested cardioplegically and fixed with
      aldehyde fixative 90 min after global ischemia at room temperature. For control,
      newborn rat hearts were fixed immediately after sacrifice. Ventricular tissue
      blocks were prepared for electron microscopy. Mitochondrial (volume-weighted mean
      volume of mitochondria) and cardiomyocyte volume (cellular edema index, CEI) were
      estimated to quantify the ischemic injury. Compared to control myocardium, CEI
      was increased by 244% +/- 39% in sham, 173% +/- 28% in Nal, 142% +/- 25% in HD,
      and 101% +/- 24% in Pla (P < 0.05 between groups). Volume-weighted mean volume of
      mitochondria was increased by 514% +/- 235% in sham, 341% +/- 110% in Nal, 458%
      +/- 149% in HD, and 175% +/- 70% in Pla. Differences between Pla and other groups
      were significant (P < 0.01 for all). No significant difference was observed
      between the other groups. Thus, ischemic injury was smallest with placebo,
      indicating a mechanism similar to preconditioning induced by the intraperitoneal
      injection. This response was attenuated by blockade of opioid receptors and
      mitochondrial potassium channels, suggesting their involvement in the elevated
      ischemia tolerance of newborn rat hearts.

PMID- 16456874
TI  - Defoliation and plasmid delivery with layer-by-layer coated colloids.
AB  - The uptake of polyelectrolyte multilayer coated colloids into cells, subsequent
      defoliation and plasmid delivery was studied by means of confocal microscopy and
      flow cytometry. Silica particles coated layer-wise with protamine and dextran
      sulfate were given to HEK 293T cells. Optimum uptake was found with protamine as
      the top layer. The particle uptake likely follows an non-receptor-mediated
      endocytotic pathway. Defoliation of polyelectrolyte multilayer coated particles
      within cells was demonstrated by the release of incorporated plasmids as
      indicated by the expression of plasmid encoded proteins using the enhanced green
      fluorescence proteine (pEGFP-C1) plasmid and a red fluorescence protein (pDsRed1
      N1) plasmid. This proves, together with the direct observation of fluorescent
      layer debris, the defoliation of coated particles and the release of layer
      components into the cytoplasm. Particle uptake and GFP expression.

PMID- 16456875
TI  - Novel functional hyperbranched polyether polyols as prospective drug delivery
      systems.
AB  - Multifunctional hyperbranched polyether polyols bearing protective poly(ethylene
      glycol) (PEG) chains with or without the folate targeting ligand at their end
      have been prepared. Solubilization in these polymers of a fluorescent probe,
      pyrene, and an anticancer drug, tamoxifen, was physicochemically investigated. It
      was found that PEG chains attached at the surface of these hyperbranched
      polymers, in addition to their well-established protective role, enhance the
      encapsulation efficiency of the polymers. The release of pyrene and tamoxifen
      observed upon addition of sodium chloride is, in most of the cases, significant
      only at concentrations exceeding the physiological extracellular concentration.
      Thus, a significant amount of the probe or drug remains solubilized inside the
      carriers, which is an encouraging result if the polymers are to be used for drug
      delivery.

PMID- 16456876
TI  - Boronate-containing copolymers: polyelectrolyte properties and sugar-specific
      interaction with agarose gel.
AB  - Copolymers of N-acryloyl-m-aminophenylboronic acid (NAAPBA) with acryamide (AA),
      N,N-dimethylacrylamide (DMAA), and N-isopropylacrylamide (NIPAM) were found to
      adsorb on cross-linked agarose gel (Sepharose CL-6B) in the pH range from 7.5
      9.2, due to specific boronate-sugar interactions. The molar percentages of
      phenylboronic acid (PBA) groups in the boronate-containing copolymers (BCCs), as
      estimated by 1H NMR spectroscopy, were 13, 10, and 16%, respectively, whereas the
      apparent ionization constants, the pKa values, of the copolymers were similar and
      equal to 9.0 +/- 0.2 at 20 degrees C. The copolymers adsorption capacities were
      in the range of 15-30 mg x ml(-1) gel (14-36 micromol pendant PBA ml(-1) gel) at
      pH 9.2 and decreased with decreasing pH value. The interaction of monomeric
      NAAPBA with Sepharose CL-6B was characterized by an equilibrium association
      constant of 53 +/- 17 M(-1), the chromatographic capacity factor k' = 1.8, and a
      total content of binding sites of 27 +/- 10 micromol x ml(-1) gel at pH 9.2. The
      weak reversible binding of monomeric NAAPBA and almost irreversible binding of
      NAAPBA copolymers to the gel at pH 9.2 suggested a multivalent character of the
      copolymer adsorption. At pH 7.5, the maximal adsorption capacity was displayed by
      the AA-NAAPBA copolymer (15 mg x ml(-1) gel). All the BCCs could be completely
      desorbed from the gel by 0.1 M fructose in aqueous buffered media with pH values
      from 7.5-9.2. The strong adsorption of AA-NAAPBA on agarose gel probably relates
      to the conformation of the copolymer in aqueous solution and provides
      opportunities for biomedical applications of the copolymer under physiological
      conditions. Multivalent, weak-affinity adsorption of BCCs to the agarose gel
      seems to be a tentative model for the copolymers' binding to oligo- and
      polysaccharides of cell membranes and mucosal surfaces.

PMID- 16456877
TI  - Novel pH sensitive block copolymer micelles for solvent free drug loading.
AB  - Novel pH sensitive biodegradable block copolymers (MPEG-PDLLA-OSM) composed of
      mono-methoxy poly(ethylene glycol) (MPEG), poly (D,L-lactide) (PDLLA) and
      sulfamethazine oligomer (OSM) were synthesized via ring-opening polymerization
      and a dicyclohexyl carboimide (DCC) coupling reaction. These copolymers had a
      relatively low critical micelle concentration (CMC) due to the strong hydrophobic
      properties of non-ionized OSM at pH 7.0. Also, the pH sensitive block copolymers
      showed the micelle-unimer transition due to the ionization-non-ionization of OSM
      in the pH range (pH 7.2-8.4) above the CMC. Due to the pH sensitive properties of
      the block copolymer, the hydrophobic drug paclitaxel (PTX) was incorporated into
      a pH sensitive block copolymer micelle by the pH induced micellization method,
      without using an organic solvent. The block copolymer micelle prepared by pH
      induced micellization showed a relatively high PTX loading efficiency, and good
      stability for 2 d at 37 degrees C. Furthermore, the PTX loaded micelle showed a
      sustained release of PTX with a small burst in vitro over 2 d. The present
      results suggest that the pH induced micellization method due to the micelle
      unimer transition of the pH sensitive block copolymer would be a novel and
      valuable drug incorporation tool for hydrophobic and protein drugs, since no
      organic solvent is involved in the formulation.

PMID- 16456878
TI  - Achilles tendon rupture and its association with fluoroquinolone antibiotics and
      other potential risk factors in a managed care population.
AB  - BACKGROUND: Case reports and observational studies have implicated
      fluoroquinolone antibiotic exposure as a risk factor for Achilles tendon rupture
      (ATR), an uncommon condition for which there are few formal studies. We sought to
      quantify the strength of association between exposure to fluoroquinolone
      antibiotics and the occurrence of ATR, accounting for other risk factors.
      METHODS: This was a case-control study nested within a health insurer cohort.
      Cases of ATR were identified and confirmed using patterns of health insurance
      claims that were validated through sampled medical record review. Information on
      risk factors, including fluoroquinolone exposure, came from health insurance
      claims. RESULTS: There were 947 cases of ATR and 18 940 controls. A dispensing of
      a fluoroquinolone antibiotic in the past 6 months was more common among ATR cases
      than controls, although not significantly so (odds ratio (OR) = 1.2; 95%
      confidence interval (CI) = 0.9-1.7), and exposure to a higher cumulative
      fluoroquinolone dose was more strongly associated (OR = 1.5, 95%CI = 1.0-2.3).
      Other risk factors for ATR were trauma (OR = 17.2, 95%CI = 14.0-20.2), male sex
      (OR = 3.0, 95%CI = 2.6-3.5), injected corticosteroid administration (OR = 2.2,
      95%CI = 1.6-2.9), obesity (OR = 2.0, 95%CI = 1.2-3.1), rheumatoid arthritis (OR =
      1.9, 95%CI = 1.0-3.7), skin or soft tissue infections (OR = 1.5, 95%CI = 0.9
      2.3), oral corticosteroids (OR = 1.4, 95%CI = 1.0-1.8), and non-fluoroquinolone
      antibiotics (OR = 1.2, 95%CI = 1.1-1.5). CONCLUSIONS: The elevation in ATR risk
      associated with fluoroquinolones was similar in magnitude to that associated with
      oral corticosteroids or non-fluoroquinolone antibiotics. Trauma and male sex were
      more strongly associated with ATR, as were obesity and injected corticosteroids.

PMID- 16456879
TI  - A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity:
      lessons learned from the bromfenac experience.
AB  - Drug-induced hepatotoxicity is the leading cause of acute liver failure (ALF) in
      the US and the most common adverse event causing drug non-approval and drug
      withdrawal by the U.S. Food and Drug Administration (FDA). Three different
      nonsteroidal anti-inflammatory drugs (NSAIDs) have been withdrawn in the UK
      and/or the US due to hepatotoxicity (bromfenac, ibufenac, and benoxaprofen). A
      systematic review of clinical trials data for these drugs was performed in an
      effort to identify possible early signals that could have predicted post
      marketing serious hepatoxicity. There were very limited published data on
      benoxaprofen and none on ibufenac or bromfenac. The publicly accessible archives
      of the FDA provided information on bromfenac. Flu-like symptoms associated with
      hepatic enzyme elevation and a case of possible drug-related hepatocellular
      jaundice may in retrospect have been signals for serious hepatotoxicity in the
      database of 1195 subjects reviewed by the FDA. Following approval, rates of acute
      liver failure for bromfenac were estimated to be in the range of 1:10 000. In
      addition, the safety databases of several drugs also accessed through FDA
      archives have been reviewed (simvastatin, tacrine, troglitazone, and
      ximelagatran). These data suggest that while ALT elevations alone do not reliably
      signal serious hepatotoxicity, elevated transaminases in association with
      symptomatic hepatitis or jaundice may be predictors of an increased risk of ALF.
      At present, however, pre-approval databases are generally not large enough to
      rule out low rates of serious hepatotoxicity. Therefore, it remains critical that
      clinicians report such cases to the FDA through the MEDWATCH system and that
      active post-marketing monitoring studies be used to identify potential rare cases
      of hepatotoxicity.

PMID- 16456880
TI  - Proteomic analysis reveals a novel role for the actin cytoskeleton in vincristine
      resistant childhood leukemia--an in vivo study.
AB  - Intrinsic or acquired resistance to vincristine (VCR), an antimicrotubule agent
      used in the treatment of childhood acute lymphoblastic leukemia (ALL), is a major
      clinical problem. Using a clinically relevant NOD/SCID mouse xenograft model of
      ALL, we established that alterations in the actin and tubulin cytoskeleton are
      involved in in vivo VCR resistance. Altered protein expression between VCR
      sensitive ALL xenografts, and xenografts with intrinsic or acquired VCR
      resistance, was identified using 2-D DIGE coupled with MS. Of the 19 proteins
      displaying altered expression, 11 are associated with the actin cytoskeleton.
      Altered expression of the actin- and/or tubulin-binding proteins gelsolin,
      moesin, ezrin, tropomyosin, CAP-G, HSP27, HSP70, TCP-1, and stathmin were
      associated with in vivo VCR resistance. The actin-regulating protein gelsolin was
      increased in both acquired and resistant leukemia as confirmed by immunoblotting
      and gene expression. The major cytoskeletal protein, gamma-actin, was down
      regulated in the VCR-resistant leukemia xenografts; in contrast, there was no
      significant change in beta-actin expression. This study provides the first
      evidence for a role of the actin cytoskeleton in intrinsic and acquired in vivo
      antimicrotubule drug resistance in childhood leukemia and highlights the power of
      2-D DIGE for the discovery of resistance markers, pharmacoproteomics, and
      signaling pathways in cancer.

PMID- 16456881
TI  - Outer membrane vesicles from group B Neisseria meningitidis delta gna33 mutant:
      proteomic and immunological comparison with detergent-derived outer membrane
      vesicles.
AB  - We compared the proteome of detergent-derived group B Neisseria meningitidis
      (MenB) outer membrane vesicles (DOMVs) with the proteome of outer membrane
      vesicles (m-OMVs) spontaneously released into culture supernatant by MenB delta
      gna33, a mutant in which the gene coding for a lytic transglycosylase homologous
      to the E. coli MltA was deleted. In total, 138 proteins were identified in DOMVs
      by 1- and 2-DE coupled with MS; 64% of these proteins belonged to the inner
      membrane and cytoplasmic compartments. By contrast, most of the 60 proteins of m
      OMVs were classified by PSORT as outer membrane proteins. When tested for their
      capacity to elicit bactericidal antibodies, m-OMVs elicited a broad protective
      activity against a large panel of MenB strains. Therefore, the identification of
      mutations capable of conferring an OMV-releasing phenotype in bacteria may
      represent an attractive approach to study bacterial membrane composition and
      organization, and to design new efficacious vaccine formulations.

PMID- 16456882
TI  - Reduction of proteins during sample preparation and two-dimensional gel
      electrophoresis of woody plant samples.
AB  - Protein extraction procedure and the reducing agent content (DTT,
      dithioerythritol, tributyl phosphine and tris (2-carboxyethyl) phosphine (TCEP))
      of the sample and rehydration buffers were optimised for European beech leaves
      and roots and Norway spruce needles. Optimal extraction was achieved with 100 mM
      DTT for leaves and needles and a mixture of 2 mM TCEP and 50 mM DTT for roots.
      Performing IEF in buffers containing hydroxyethyldisulphide significantly
      enhanced the quality of separation for all proteins except for acidic root
      proteins, which were optimally focused in the same buffer as extracted.

PMID- 16456883
TI  - Proteomic and biochemical analyses of in vitro carcinogen-induced lung cell
      transformation: synergism between arsenic and benzo[a]pyrene.
AB  - Chronic coexposures to carcinogens inorganic arsenic and benzo[a]pyrene (B[a]P)
      are common in the living environment. However, little is known about their
      effects exerted at the proteome level. Our previous study in rat lung epithelial
      cells showed that cell transformation frequency increased by more than 100-fold
      when arsenic was given in combination with B[a]P than cells either exposed to
      arsenic or B[a]P alone. This demonstrated a synergism between them. Here, we
      reported that alterations to the proteome varied and were more pronounced in the
      transformed cells that were exposed to a combination of arsenic and B[a]P than to
      B[a]P and much less to arsenic alone when compared to passage-matched control
      cells. In general, three proteins belonging to intermediate filaments were found
      to be significantly down-regulated and six proteins belonging to antioxidative
      stress-, chaperone-, and glycolytic proteins were up-regulated in these
      transformed cells. These transformed cells were also associated with an increase
      of proliferation and de-differentiation. Taken together, our findings suggest
      that although arsenic or B[a]P alone is sufficient to induce cell transformation
      and alter the proteome to a similar extent, the effects of coexposure are much
      more pronounced. This further substantiates the notion that these carcinogens act
      in concert during cocarcinogenesis.

PMID- 16456885
TI  - SPLASH: systematic proteomics laboratory analysis and storage hub.
AB  - In the field of proteomics, the increasing difficulty to unify the data format,
      due to the different platforms/instrumentation and laboratory documentation
      systems, greatly hinders experimental data verification, exchange, and
      comparison. Therefore, it is essential to establish standard formats for every
      necessary aspect of proteomics data. One of the recently published data models is
      the proteomics experiment data repository [Taylor, C. F., Paton, N. W., Garwood,
      K. L., Kirby, P. D. et al., Nat. Biotechnol. 2003, 21, 247-254]. Compliant with
      this format, we developed the systematic proteomics laboratory analysis and
      storage hub (SPLASH) database system as an informatics infrastructure to support
      proteomics studies. It consists of three modules and provides proteomics
      researchers a common platform to store, manage, search, analyze, and exchange
      their data. (i) Data maintenance includes experimental data entry and update,
      uploading of experimental results in batch mode, and data exchange in the
      original PEDRo format. (ii) The data search module provides several means to
      search the database, to view either the protein information or the differential
      expression display by clicking on a gel image. (iii) The data mining module
      contains tools that perform biochemical pathway, statistics-associated gene
      ontology, and other comparative analyses for all the sample sets to interpret its
      biological meaning. These features make SPLASH a practical and powerful tool for
      the proteomics community.

PMID- 16456884
TI  - Functional peptide microarrays for specific and sensitive antibody diagnostics.
AB  - Peptide microarrays displaying biologically active small synthetic peptides in a
      high-density format provide an attractive technology to probe complex samples for
      the presence and/or function of protein analytes. We present a new approach for
      manufacturing functional peptide microarrays for molecular immune diagnostics.
      Our method relies on the efficiency of site-specific solution-phase coupling of
      biotinylated synthetic peptides to NeutrAvidin (NA) and localized microdispensing
      of peptide-NA-complexes onto activated glass surfaces. Antibodies are captured in
      a sandwich manner between surface immobilized peptide probes and fluorescence
      labeled secondary antibodies. Our work includes a total of 54 peptides derived
      from immunodominant linear epitopes of the T7 phage capsid protein, Herpes
      simplex virus glycoprotein D, c-myc protein, and three domains of the Human
      coronavirus polymerase polyprotein and their cognate mAbs. By using spacer
      molecules of different type and length for NA-mediated peptide presentation, we
      show that the incorporation of a minimum spacer length is imperative for antibody
      binding, whereas the peptide immobilization direction has only secondary
      importance for antibody affinity and binding. We further demonstrate that the
      peptide array is capable of detecting low-picomolar concentrations of mAbs in
      buffered solutions and diluted human serum with high specificity.

PMID- 16456888
TI  - Oscillating electrolytes.
AB  - Chemical oscillations are driven by the gradient of the chemical potential so
      that they can appear in systems where the substances are not in chemical
      equilibrium. We show that under the influence of the electric field,
      concentrations of electrically charged substances in solutions can oscillate even
      if the system is in chemical equilibrium. The driving force here is not the
      gradient of the chemical potential but rather the gradient of the electric
      potential. Utilizing CE we found periodic structures invoked by the application
      of a constant driving voltage in BGEs possessing complex eigenmobilities. By
      analogy with the behavior of dynamic systems, complex eigenmobilities implicate
      that the system will be unstable. Instead of forming system zones (system peaks)
      in the separation channel (capillary) the originally uniform concentration of
      electrolyte constituents becomes periodically disturbed when the electric current
      passes through it.

PMID- 16456889
TI  - Capillary electrophoresis for thermodynamic and kinetic studies of peptidyl
      proline isomerization by the theoretical plate height model.
AB  - The theoretical plate height model, extended to include reactive CE, is used to
      calculate equilibrium constants and rate constants for the reversible, first
      order isomerization of proline dipeptides. This model is consistent with
      chromatographic theory and enables calculation of equilibrium constants from
      velocity and calculation of rate constants from plate height. Thermodynamic and
      kinetic parameters for isomerization of Ala-Pro and Phe-Pro are calculated by
      using the plate height model, and are shown to be in good agreement with
      literature values. Additionally, the efficacy of the plate height model is
      compared to ChromWin, an existing simulation method for calculating rate
      constants from zone profiles. It is shown that ChromWin and the plate height
      model are complementary methods. ChromWin is best used for calculating rate
      constants for reactions that are far from steady state, where the zone profiles
      exhibit plateau formation. On the other hand, the plate height model is best used
      for calculating rate constants for reactions that are at or near steady state,
      where the zone profiles exhibit a single zone containing both reacting species.

PMID- 16456890
TI  - Electroosmotic flow in a rectangular channel with variable wall zeta-potential:
      comparison of numerical simulation with asymptotic theory.
AB  - Electroosmotic flow in a straight micro-channel of rectangular cross-section is
      computed numerically for several situations where the wall zeta-potential is not
      constant but has a specified spatial variation. The results of the computation
      are compared with an earlier published asymptotic theory based on the lubrication
      approximation: the assumption that any axial variations take place on a long
      length scale compared to a characteristic channel width. The computational
      results are found to be in excellent agreement with the theory even when the
      scale of axial variations is comparable to the channel width. In the opposite
      limit when the wavelength of fluctuations is much shorter than the channel width,
      the lubrication theory fails to describe the solution either qualitatively or
      quantitatively. In this short wave limit the solution is well described by
      Ajdari's theory for electroosmotic flow between infinite parallel plates (Ajdari,
      A., Phys. Rev. E 1996, 53, 4996-5005.) The infinitely thin electric double layer
      limit is assumed in the theory as well as in the simulation.

PMID- 16456891
TI  - A method for simultaneously determining the zeta potentials of the channel
      surface and the tracer particles using microparticle image velocimetry technique.
AB  - The zeta potentials of channel surfaces and tracer particles are of importance to
      the design of electrokinetic microfluidic devices, the characterization of
      channel materials, and the quantification of the microparticle image velocimetry
      (microPIV) measurement of EOFs. A method is proposed to simultaneously measure
      the zeta potentials of the channel surface and the tracer particles in aqueous
      solutions using the microPIV technique. Through the measurement of the steady
      velocity distributions of the tracer particles in both open- and closed-end
      rectangular microchannels under the same water chemistry condition, the
      electrophoretic velocity of the tracer particles and the EOF field of the
      microchannel are determined using the expressions derived in this study for the
      velocity distributions of charged tracer particles in the open- and closed-end
      rectangular microchannels. Thus, the zeta potentials of the tracer particles and
      the channel surfaces are simultaneously obtained using the least-square method to
      fit the microPIV measured velocity distribution of the tracer particles.
      Measurements were carried out with a microPIV system to determine the zeta
      potentials of the channel wall and the fluorescent tracer particles in deionized
      water and sodium chloride and boric acid solutions of various concentrations.

PMID- 16456892
TI  - Assessment of Joule heating and its effects on electroosmotic flow and
      electrophoretic transport of solutes in microfluidic channels.
AB  - Joule heating is inevitable when an electric field is applied across a conducting
      medium. It would impose limitations on the performance of electrokinetic
      microfluidic devices. This article presents a 3-D mathematical model for Joule
      heating and its effects on the EOF and electrophoretic transport of solutes in
      microfluidic channels. The governing equations were numerically solved using the
      finite-volume method. Experiments were carried out to investigate the Joule
      heating associated phenomena and to verify the numerical models. A rhodamine B
      based thermometry technique was employed to measure the solution temperature
      distributions in microfluidic channels. The microparticle image velocimetry
      technique was used to measure the velocity profiles of EOF under the influence of
      Joule heating. The numerical solutions were compared with experimental results,
      and reasonable agreement was found. It is found that with the presence of Joule
      heating, the EOF velocity deviates from its normal "plug-like" profile. The
      numerical simulations show that Joule heating not only accelerates the sample
      transport but also distorts the shape of the sample band.

PMID- 16456893
TI  - Theoretical and nomenclatural considerations of capillary electrochromatography
      with monolithic stationary phases.
AB  - During the past decade, CEC has been one of the few novel achievements in the
      field of separation science attracting a wide interest. The technology progress
      permitted the realization of the long-sought idea to employ an electroosmotically
      driven flow through the columns improving the separations in terms of both
      resolution and efficiency. The early practical obstacles related to the use of
      conventional bead-packed columns have been solved by the introduction of
      continuous beds, also known as monoliths. Hitherto, various synthesis approaches
      have been successfully developed producing monolithic beds in situ in capillary
      columns, sharing similar physical structure built up of tiny particles (in the
      sub-microm range) that are covalently linked together and to the capillary wall.
      Parallel with the practical column technology studies, the theory of
      electrochromatography has been continuously developed, focusing on such basic
      issues as EOF characterization, separation efficiency, and peak dispersion
      effects. This review provides a short introduction to the theory of CEC with
      special attention to monolithic separation beds. The paper also summarizes the
      latest achievements in CEC and discusses the nomenclature, EOF characteristics,
      and some specific advantages of monolithic column technology.

PMID- 16456895
TI  - Improved hypothesis testing for coefficients in generalized estimating equations
      with small samples of clusters.
AB  - The sandwich standard error estimator is commonly used for making inferences
      about parameter estimates found as solutions to generalized estimating equations
      (GEE) for clustered data. The sandwich tends to underestimate the variability in
      the parameter estimates when the number of clusters is small, and reference
      distributions commonly used for hypothesis testing poorly approximate the
      distribution of Wald test statistics. Consequently, tests have greater than
      nominal type I error rates. We propose tests that use bias-reduced linearization,
      BRL, to adjust the sandwich estimator and Satterthwaite or saddlepoint
      approximations for the reference distribution of resulting Wald t-tests. We
      conducted a large simulation study of tests using a variety of estimators
      (traditional sandwich, BRL, Mancl and DeRouen's BC estimator, and a modification
      of an estimator proposed by Kott) and approximations to reference distributions
      under diverse settings that varied the distribution of the explanatory variables,
      the values of coefficients, and the degree of intra-cluster correlation (ICC).
      Our new method generally worked well, providing accurate estimates of the
      variability of fitted coefficients and tests with near-nominal type I error rates
      when the ICC is small. Our method works less well when the ICC is large, but it
      continues to out-perform the traditional sandwich and other alternatives.

PMID- 16456896
TI  - New evidence for the origin of intracranial germ cell tumours from primordial
      germ cells: expression of pluripotency and cell differentiation markers.
AB  - Primary intracranial germ cell tumours are rare neoplasms that occur in children
      and adolescents. This study examined both the biology and the origin of these
      tumours, as it has been hypothesized that they originate from a totipotent
      primordial germ cell. We applied recent knowledge from gonadal germ cell tumours
      and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT
      3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ
      cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the
      protein level was analysed in 21 children and young adults with intracranial
      germinomas and non-germinomas, contributing to a careful description of these
      unusual tumours and adding to the understanding of pathogenesis. Stem cell
      related proteins were highly expressed in intracranial germ cell tumours, and
      many similarities were detected with their gonadal equivalents, including a close
      similarity with primordial germ cells. A notable difference was the sex-specific
      expression of TSPY, a gene previously implicated in the origin of gonadoblastoma.
      TSPY was only detected in germ cell tumours in the central nervous system (CNS)
      from males, suggesting that it is not required for the initiation of malignant
      germ cell transformation. The expression of genes associated with embryonic stem
      cell pluripotency in CNS germ cell tumours strongly suggests that these tumours
      are derived from cells that retain, at least partially, an embryonic stem cell
      like phenotype, which is a hallmark of primordial germ cells.

PMID- 16456897
TI  - Sample size and statistical power assessing the effect of interventions in the
      context of mixture distributions with detection limits.
AB  - Often in randomized clinical trials and observational cohort studies, a non
      negative continuously distributed response variable is measured in treatment and
      control groups. In the presence of true zeros for the response variable, a two
      part zero-inflated log-normal model (which assumes that the data has a
      probability mass at zero and a continuous response for values greater than zero)
      is usually recommended. However, in some environmental health and human
      immunodeficiency virus (HIV) studies, quantitative assays for metabolites of
      toxicants, or quantitative HIV RNA measurements are subject to left-censoring due
      to values falling below the limit of detection (LD). Here, a zero-inflated log
      normal mixture model is often suggested since true zeros are indistinguishable
      from left-censored values due to the LD. When the probabilities of true zeros in
      the two groups are not restricted to be equal, the information contributed by
      values falling below LD is used only to estimate the probability of true zeros in
      the context of mixture distributions. We derived the required sample size to
      assess the effect of a treatment in the context of mixture models with equal and
      unequal variances based on the left-truncated log-normal distribution. Methods
      for calculation of statistical power are also presented. We calculate the
      required sample size and power for a recent study estimating the effect of
      oltipraz on reducing urinary levels of the hydroxylated metabolite aflatoxin M(1)
      (AFM(1)) in a randomized, placebo-controlled, double-blind phase IIa
      chemoprevention trial in Qidong, China. A Monte Carlo simulation study is
      conducted to investigate the performance of the proposed methods.

PMID- 16456899
TI  - Modified calculations of hydrocarbon thermodynamic properties.
AB  - A test set of 65 hydrocarbons was examined to elucidate theoretically their
      thermodynamic properties by performing the density-functional theory (DFT) and ab
      initio calculations. All the calculated data were modified using a three
      parameter calibration equation and the least-squares approach, to determine
      accurately enthalpies of formation (DeltaH(f)), entropies (S), and heat
      capacities (C(p)). Calculation results demonstrated that the atomization energies
      of all compounds exhibited an average absolute relative error ranging between
      0.11- 0.13%, and an DeltaH(f) of formation with a mean absolute absolute error
      (M.|A.E.|) ranging from only 5.7-6.8 kJ/mol (1.3-1.6 kcal/mol) (i.e., those
      results correlated with those of Dr. Herndon's 1.1 kcal/mol). Additionally, the
      entropy ranged from 3.5-4.2 J/mol K (0.8-1.0 cal/mol K) M.|A.E.|; a heat capacity
      between 2.3-2.9 J/mol K (0.5-0.7 cal/mol K) M.|A.E.| was obtained as well.

PMID- 16456898
TI  - Expression of Lewis antigens and their precursors in gastric mucosa: relationship
      with Helicobacter pylori infection and gastric carcinogenesis.
AB  - Lewis (Le)-associated antigens are carbohydrates that are related biochemically
      to the ABO blood groups, and may have a role in Helicobacter pylori adherence. To
      evaluate their relationship to clinicopathological outcomes, gastric Le
      expression, including type 1 precursor, type 1 H, Le(a), Le(b), Le(x), Le(y) and
      sialylated Le(a) (CA19-9), was evaluated immunohistochemically in 233 gastric
      biopsy specimens obtained at routine gastroscopy. Expression was also
      investigated in gastric tissues showing chronic gastritis, intestinal metaplasia,
      and carcinoma from 42 patients with gastric cancer. A polymerase chain reaction
      was performed for H. pylori and the bacterial babA2 gene. We identified type 1
      precursor expression in 34.3%, type 1 H in 55.8%, Le(a) in 44.2%, Le(b) in 82.0%,
      Le(x) in 44.2%, Le(y) 56.7%, and CA19-9 in 16.3% of the 233 gastric biopsy
      specimens. Expression of type 1 H, Le(b), and CA19-9 was significantly associated
      with H. pylori infection and histological features (p < 0.05), and expression of
      type 1 H was an independent predictive factor for H. pylori infection by
      multivariate logistic regression (p = 0.020). Positivity for the babA2 genotype
      correlated significantly with H. pylori infection and type 1 H expression in
      gastric biopsy specimens (p < 0.05). The babA2 genotype was more frequent in
      gastric mucosa from the gastric cancer patients than in gastric biopsy specimens
      from routine gastroscopy (p = 0.009). In the 42 gastric cancer patients, the
      frequency of type 1 precursor, Le(a), and Le(x) expression was significantly
      higher in intestinal metaplasia and carcinoma than in chronic gastritis (p <
      0.05), but the frequency of type 1 H and Le(b) expression was significantly lower
      in intestinal metaplasia and carcinoma (p < 0.05). In conclusion, Le expression,
      especially that of type 1 H, was significantly associated with
      clinicopathological features. In gastric cancer patients, Le expression was
      altered in intestinal metaplasia and carcinoma in comparison with chronic
      gastritis.

PMID- 16456900
TI  - Enzymatic synthesis and photoswitchable enzymatic cleavage of a peptide-linked
      rotaxane.

PMID- 16456901
TI  - A fluid membrane-based soluble ligand-display system for live-cell assays.

PMID- 16456902
TI  - The leading role of association in framework modification of highly siliceous
      zeolites with adsorbed methylamine.
AB  - Affinity index (AT value), adsorption heat, X-ray diffraction (XRD), and 13C and
      29Si magic-angle spinning (MAS) NMR, FTIR, and Raman spectroscopies were used to
      study the interaction of highly siliceous MFI-, FAU-, and FER-type zeolites with
      adsorbed methylamine (MA). Compared with the data for methanol, the much higher
      AT values and adsorption heats, and significant changes in XRD patterns, 29Si MAS
      NMR spectra, and FTIR spectra for the zeolites after adsorption of MA, revealed a
      strong hydrogen-bonding interaction between the perfect framework of the zeolites
      and the adsorbed MAs. This interaction results from the fact that the H atom of
      the amine group attacks the [Si-O] framework to form a Si-OHN bond, which leads
      to the appearance of Si-N bonds in the zeolites at 323 K. Therefore, the zeolite
      framework can be modified with MA under mild conditions. The highly siliceous MFI
      zeolite and the H-ZSM-5 zeolite with SiO2/Al2O3=31:1 were modified with MA and
      investigated by temperature-programmed desorption of CO2. The modified zeolites
      exhibited greatly enhanced basic properties in comparison with those of the raw
      materials. The influence of defects in the zeolite on the adsorption and the
      interaction with MA is discussed.

PMID- 16456903
TI  - Photoswitched wettability on inverse opal modified by a self-assembled azobenzene
      monolayer.

PMID- 16456904
TI  - Ordering spatiotemporal chaos in small-world neuron networks.

PMID- 16456905
TI  - Mathematical modelling and simulation of adsorption processes at spherical
      microparticles.
AB  - A model for the adsorption process at spherical microparticles under transient
      diffusion conditions has been developed and solved using numerical simulation.
      This model allowed us to demonstrate that the system is controlled by two main
      dimensionless parameters: the adsorption rate constant ka' and the saturation
      parameter beta. Analytical models for the adsorption process at spherical
      microparticles under steady-state mass transport conditions have been derived.
      These models use previously developed empirical relationships for the calculation
      of the mass transfer coefficient (kc). The properties of the system were studied
      for both the case where mass transport is described by diffusion only and the
      case where it is the result of a coupled diffusion/convection process. These
      mathematical tools were then used to analyse the results obtained for the uptake
      of CuII by glassy carbon powder modified with the monomer L-cysteine methyl ester
      and to extract a minimum value for the adsorption rate constant which was found
      to be of the order of 10(-4) cm s(-1).

PMID- 16456906
TI  - Preparation of a nanowire-structured polyaniline composite and gas sensitivity
      studies.
AB  - To obtain organic nanowire sensors with high sensitivity and rapid response
      times, based on the inducement effect of surfactants during in situ
      polymerization, nanostructured polyaniline composites are obtained by using a
      chemical oxidation method by adding a small amount of surfactant. A casting
      method is employed on interdigitated carbon electrodes. The gas sensitivity to a
      series of chemical vapors is examined at room temperature. The results indicate
      that polyaniline with regular nanowire structure is obtained when succinic acid
      is added. The gas sensitivity and response rates of a film with nanowire
      structure are much better than those of conventional polyaniline films produced
      by means of organic solution spin coating methods. The film described in this
      work shows good selectivity to trimethylamine and other related gases and, the
      reaction being reversible with the use of high-purity nitrogen.

PMID- 16456907
TI  - Unprecedented ROMP activity of low-valent rhenium-nitrosyl complexes: Mechanistic
      evaluation of an electrophilic olefin metathesis system.
AB  - The reaction of [Re(H)(NO)2(PR3)2] complexes (1 a: R = PCy3; 1 b: R = PiPr3) with
      [H(OEt2)2][BAr(F)4] ([BAr(F)4] = tetrakis{3,5-bis(trifluoromethyl)phenyl}borate)
      in benzene at room temperature gave the corresponding cations
      [Re(NO)2(PR3)2][BAr(F)4] (2 a and 2 b). The addition of phenyldiazomethane to
      benzene solutions of 2 a and 2 b afforded the moderately stable cationic
      rhenium(I)-benzylidene-dinitrosyl-bis(trialkyl)phosphine complexes 3 a and 3 b as
      [BAr(F)4]- salts in good yields. The complexes 2 a and 2 b catalyze the ring
      opening metathesis polymerization (ROMP) of highly strained nonfunctionalized
      cyclic olefins to give polymers with relatively high polydispersity indices, high
      molecular weights and over 80 % Z configuration of the double bonds in the chain
      backbone. However, these complexes do not show metathesis activity with acyclic
      olefins. The benzylidene derivatives 3 a and 3 b are almost inactive in ROMP
      catalysis with norbornene and in olefin metathesis. NMR experiments gave the
      first hints of the initial formation of carbene complexes from
      [Re(NO)2(PR3)2][BAr(F)4] (2 a and 2 b) and norbornene. In a detailed mechanistic
      study ESI-MS/MS measurements provided further evidence that the carbene formation
      is initiated by a unique reaction sequence where the cleavage of the strained
      olefinic bond starts with phosphine migration forming a cyclic ylide-carbene
      complex, capable of undergoing metathesis with alternating rhenacyclobutane
      formation and cycloreversion reactions ("ylide" route). However, even at an early
      stage the ROMP propagation route is expected to merge into an "iminate" route by
      attack by the ylide function on one of the N(NO) atoms followed by phosphine
      oxide elimination. The formation of phosphine oxide was confirmed by NMR
      spectroscopy. The proposed mechanism is supported further by detailed DFT
      calculations.

PMID- 16456908
TI  - Infrared-spectroscopic and density-functional-theory investigations of the LaCO,
      La2[eta2(mu2-C,O)], and c-La2(mu-C)(mu-O) molecules in solid argon.
AB  - Reactions of laser-ablated lanthanum atoms with CO molecules in solid argon have
      been studied. The neutral lanthanum monocarbonyl (LaCO), produced upon sample
      deposition at 7 K, exhibits a C-O stretching frequency of 1772.7 cm(-1); to the
      best of our knowledge this is the lowest yet observed for a terminal CO in a
      neutral metal-carbonyl molecule (MCO, M = metal atom), implying anomalously
      enhanced metal-to-CO back-bonding. The infrared (IR) absorption band at 1145.9
      cm(-1) is assigned to the C-O stretching mode of the side-on-bonding CO in the
      La2[eta2(mu2-C,O)] molecule. This CO-activated molecule undergoes an UV/Vis
      photoinduced rearrangement to the CO-dissociated molecule, c-La2(mu-C)(mu-O).
      Density functional theory (DFT) calculations have been performed on these
      molecules, the results of which lend strong support to the experimental
      assignments of the IR spectra. LaCO is predicted to have a quartet ground state,
      corresponding to a linear geometry. Its formation involves La 6s-->4f promotion,
      which increases the strength of La-CO bonding by decreasing the sigma repulsion
      and, remarkably, by increasing the La 5d and 4f-->CO 2pi back-bonding. The
      observations schematically depict the whole process, starting with the
      interaction of CO with metal and ending with CO dissociation by the lanthanum
      dimer.

PMID- 16456909
TI  - Platinum- and gold-catalyzed rearrangement reactions of propargyl acetates: total
      syntheses of (-)-alpha-cubebene, (-)-cubebol, sesquicarene and related terpenes.
AB  - Propargyl acetates, in the presence of catalytic amounts of late transition-metal
      salts such as PtCl(2) or AuCl(3), represent synthetic equivalents of alpha
      diazoketones. This notion is corroborated by a concise approach to various
      sesquiterpene natural products starting from readily available substrates.
      Specifically, (+)-carvomenthone (17) is converted into propargyl acetate (S)-26
      by a sequence involving Stille cross-coupling of its kinetic enol triflate 18,
      regioselective hydroboration/oxidation of the resulting 1,3-diene 19, and
      addition of an alkynyl cerium reagent to aldehyde 21 thus obtained. Since the
      latter step was found to be unselective, the configuration of the reacting
      propargyl acetate was unambiguously set by oxidation followed by
      diastereoselective transfer hydrogenation by using Noyori's catalyst 25. Compound
      (S)-26, on treatment with PtCl(2) in toluene, converted exclusively to the
      tricyclic enol acetate 27, which was saponified to give norcubebone 11 in
      excellent overall yield. The conversion of this compound into the sesquiterpene
      alcohol (-)-cubebol (6) was best achieved with MeCeCl(2) as the nucleophile,
      whereas the formation of the parent hydrocarbon (-)-alpha-cubebene (4) was
      effected in excellent yield by recourse to iron-catalyzed cross coupling
      methodology developed in this laboratory. Since norketone 11 has previously been
      transformed into (-)-beta-cubebene (5) as well as (-)-4-epicubebol 8, our
      approach constitutes formal total syntheses of these additional natural products
      as well. Along similar lines, the readily available propargyl acetates 1, 33 and
      47 were shown to give access to 2-carene 44, sesquicarene 39, and episesquicarene
      51 in excellent overall yields. In this series, however, the cycloisomerization
      reaction was best achieved with catalytic amounts of AuCl(3) in 1,2
      dichloroethane as the solvent. In addition to these preparative results, our data
      provide some insight into the mechanism of these remarkable skeletal
      rearrangement reactions. Transformations of this type are likely triggered by
      initial coordination of the alkyne unit of the substrate to the carbophilic
      transition-metal cation. Formal attack of the alkene moiety onto the resulting pi
      complex engenders the formation of an electrophilic cyclopropyl carbene species
      which subsequently reacts with the adjacent acetate unit to give the final
      product. The alternative phasing of events, implying initial attack of the
      acetate (rather than the alkene moiety) onto the metal-alkyne complex, is
      inconsistent with the stereochemical data obtained during this total synthesis
      campaign.

PMID- 16456910
TI  - Supramolecular template-directed synthesis of perfect phenelenediimino-bridged
      ladderlike polyphenylsiloxanes.
AB  - A template synthesis of the soluble, high molecular weight (Mw), and perfect p
      phenylenediimino (p-PDA)-bridged ladderlike polyphenylsiloxane (PLPS) is
      reported. First, N,N'-bis(phenyldichlorosilyl)-p-PDA monomers were self-assembled
      into a perfect ladder superstructure (LS) by concerted interaction of aromatic pi
      pi stacking and hydrogen bonding. Then the LS underwent a novel stoichiometric
      hydrolysis/dehydrochlorination-condensation reaction instead of the usual
      hydrolysis/dehydration-condensation reaction, leading to the PLPS. The perfect
      ladder structures of both the PLPS and, in particular, the unstable
      supramolecular LS were confirmed as follows. 1) There are two Bragg peaks in
      solid and/or solution X-ray diffraction (XRD) spectra representing the ladder
      width (w) and ladder thickness (t); these peaks were consistent with those
      calculated by molecular simulation. 2) Both the PLPS and LS have extremely sharp
      absorption peaks with small half-peak widths (Delta(1/2) < 0.3 ppm) in 29Si NMR
      spectra, suggesting the presence of the perfect ladder structure for PLPS and LS.
      3) Moreover, no noticeable absorption peaks for the Si-OH and NH2 groups were
      observed in FT-IR and 29Si NMR spectra, indicating that the Si-N bond of the
      [triple bond]Si-NH-C6H4-NH-Si[triple bond] ladder rung of PLPS and LS is not
      cleaved. 4) Both PLPS and LS show similar emission peaks (in fluorescence
      spectroscopy) attributed to the excimer formed by face-to face pi-pi stacking of
      phenyl groups along the ladder chain rather than a branched direction. 5)
      Differential scanning calorimetry (DSC) measurements indicate a high glass
      temperature (Tg = 176.4 degrees C) for PLPS. As circumstantial evidence, this
      result further indicates very high stiffness of PLPSs ladder backbone as compared
      with flexible single-chain polyphenylmethylsiloxane with a low Tg = -69.4 degrees
      C.

PMID- 16456911
TI  - Identification of isoenzymes using matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry.
AB  - The identification of isoforms is one of the great challenges in proteomics due
      to the large number of identical amino acids preventing their separations by two
      dimensional electrophoresis. Matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOFMS) has become a rapid and sensitive tool in
      proteomics, notably with the new instrumental improvements. In this study, we
      used several acquisition modes of MALDI-TOFMS to identify isoforms of porcine
      glutathiones S-transferase. The use of multiple proteases coupled to the
      different acquisition modes of MALDI-TOFMS (linear, reflectron, post-source decay
      (PSD) and in-source decay, positive and negative modes) allowed the
      identification of two sequences. Moreover, a third sequence is pointed out from a
      PSD study of a tryptic ion revealing the modification of the amino acid tyrosine
      146 to phenylalanine.

PMID- 16456912
TI  - Radiation to shrink brain tumor improves cognitive function.

PMID- 16456913
TI  - Walking slows progress of peripheral artery disease (PAD).

PMID- 16456914
TI  - New patient-activated pain control device.

PMID- 16456915
TI  - Cataract surgery may be complicated by prostate drugs.

PMID- 16456916
TI  - Reducing trans-fatty acid in french fries.

PMID- 16456917
TI  - Overweight? Watch your blood pressure.

PMID- 16456918
TI  - Inflammation: the elusive common denominator. Inflammation underlies a host of
      common illnesses; scientists think they're beginning to crack the code.

PMID- 16456919
TI  - I've taken methotrexate for several months to control my rheumatoid arthritis,
      but the bouts of upset stomach have become too much. I read that folic acid can
      counteract the side effects of methotrexate. Can you tell me more about it?

PMID- 16456920
TI  - I understand that older women should take 1,000-1,500 mg of calcium every day. I
      am 60, and my doctor recommends calcium citrate. However, a physical therapist I
      am seeing for a back problem says to take Os Cal. Which is best?

PMID- 16456921
TI  - I had radiation for acne when I was young. I've been told that this places me at
      risk for the development of thyroid cancer. How should I be monitored?

PMID- 16456922
TI  - Combo drug therapy beneficial for new cases of multiple myeloma.

PMID- 16456923
TI  - Women with family breast cancer history have no increased risk of ovarian cancer.

PMID- 16456924
TI  - Mutant huntingtin represses CBP, but not p300, by binding and protein
      degradation.
AB  - Huntington's disease can be used as a model to study neurodegenerative disorders
      caused by aggregation-prone proteins. It has been proposed that the entrapment of
      transcription factors in aggregates plays an important role in pathogenesis. We
      now report that the transcriptional activity of CBP is already repressed in the
      early time points by soluble mutant huntingtin, whereas the histone acetylase
      activity of CBP/p300 is gradually diminished over time. Mutant huntingtin bound
      much stronger to CBP than normal huntingtin, possibly contributing to repression.
      Especially at the later time points, CBP protein level was gradually reduced via
      the proteasome pathway. In sharp contrast, p300 was unaffected by mutant
      huntingtin. This selective degradation of CBP was absent in spinocerebellar
      ataxia 3. Thus, mutant huntingtin specifically affects CBP and not p300 both at
      the early and later time points, via multiple mechanisms. In addition to the
      reduction of CBP, also the altered ratio of these closely related histone acetyl
      transferases may affect chromatin structure and transcription and thus contribute
      to neurodegeneration.

PMID- 16456925
TI  - Internalization of a GFP-tetanus toxin C-terminal fragment fusion protein at
      mature mouse neuromuscular junctions.
AB  - The distribution, dynamics, internalization, and retrograde axonal traffic of a
      fusion protein composed of green fluorescent protein (GFP)and the atoxic C
      terminal fragment of tetanus toxin (TTC) were studied after its in vivo
      injection. Confocal microscopy and immuno-gold electron microscopy revealed that
      the fusion protein (GFP-TTC) rapidly clustered in motor nerve terminals of the
      neuromuscular junction. Clathrin-coated pits, and axolemma infoldings located
      between active zones appeared to be involved in the internalization of the fusion
      protein. Biochemical analysis of detergent-extracted neuromuscular preparations
      showed that the GFP-TTC fusion protein was associated with lipid microdomains. We
      suggest that GFP-TTC clustering in these lipid microdomains favors the
      recruitment of other proteins involved in its endocytosis and internalization in
      motor nerve terminals. During its retrograde trafficking, GFP-TTC accumulated
      indifferent axonal compartments than those used by cholera toxin B-subunit
      suggesting that these two proteins are transported by different pathways and
      cargos.

PMID- 16456926
TI  - Transcriptional changes during neuronal death and replacement in the olfactory
      epithelium.
AB  - The olfactory epithelium has the unusual ability to replace its neurons.We forced
      replacement of mouse olfactory sensory neurons by bulbectomy. Microarray,
      bioinformatics, and in situ hybridization techniques detected a rapid shift in
      favor of pro-apoptotic proteins, a progressive immune response by macrophages and
      dendritic cells, and identified or predicted 439 mRNAs enriched in olfactory
      sensory neurons, including gene silencing factors and sperm flagellar proteins.
      Transcripts encoding cell cycle regulators, axonogenesis proteins, and
      transcription factors and signaling proteins that promote proliferation and
      differentiation were increased at 5-7 days after bulbectomy and were expressed by
      basal progenitor cells or immature neurons. The transcription factors included
      Nhlhl, Hes6, Lmycl, c-Myc, Mxd4, Idl,Nmycl, Cited2, c-Myb, Mybll, Tead2, Dpl,
      Gata2, Lmol, and Soxll. The data reveal significant similarities with embryonic
      neurogenesis and make several mechanistic predictions, including the roles of the
      transcription factors in the olfactory sensory neuron lineage.

PMID- 16456927
TI  - Purified mouse dopamine neurons thrive and function after transplantation into
      brain but require novel glial factors for survival in culture.
AB  - Cell replacement therapy in Parkinson's disease depends on a reliable source of
      purified dopamine (DA) neurons (PDN) and the identification of factors relevant
      to their survival. Our goal was to genetically tag and purify by flow cytometry
      embryonic midbrain DA neurons from a transgenic mouse line carrying 11 kb of
      human tyrosine hydroxylase promoter driving expression of the enhanced green
      fluorescent protein(GFP) for studies in vivo and in vitro. A 99% purification of
      GFP+ cells was achieved. When transplanted into 6-hydroxydopamine-treated rat
      striatum, PDN survived, became well-integrated and produced recovery from
      amphetamine-induced motor behaviors. However, when grown in culture, PDN died
      within days of plating. No known growth factors prevented PDN death as did
      incubation with novel factors in glia/glial-conditioned media. We conclude that
      GFP-tagged DA neurons can be purified to homogeneity and can survive and function
      when grown with glial factors in vitro or after transplantation in vivo.

PMID- 16456928
TI  - Assembly of the N-cadherin complex during synapse formation involves uncoupling
      of p120-catenin and association with presenilin 1.
AB  - N-cadherin is an adhesion receptor that participates in both interaction between
      immature pre- and postsynaptic neurons and in the stabilization and function of
      matured neuron-neuron synapses. To better understand how the N-cadherin complex
      contributes to synapse formation, we examined its distribution and composition
      during synapse formation in the chick ciliary neurons. It was found that at early
      phases of synaptogenesis, N-cadherin is distributed in small clusters on the cell
      surface and primarily associates with p120-catenin and 3-catenin. In contrast, as
      synaptic contacts matured, larger N-cadherin clusters were found localized
      adjacent to the active zone and associated with PSI and y-catenin, while p120-
      and 3-catenin were dispersed among other cell regions, including axons. As it is
      known that PSI binds y-catenin and that uncoupled p120-catenin can alter the
      cytoskeleton via its effect on Rho GTPases, these changes in the molecular
      composition of the N-cadherin complex (represented by the uncoupling of p120
      catenin and association with PS1) may correspond to distinct functional states of
      the complex involved in synaptic maturation.

PMID- 16456930
TI  - Overexpression of drebrin A in immature neurons induces the accumulation of F
      actin and PSD-95 into dendritic filopodia, and the formation of large abnormal
      protrusions.
AB  - Drebrin A is a neuron-specific F-actin binding protein, and plays a pivotal role
      in the spine formation. In this study, we expressed drebrin A tagged with green
      fluorescent protein (GFP-DA) in hippocampal neurons at 7-9 days in vitro when
      presynaptic terminals are not fully maturated. GFP-DA was accumulated in
      dendritic protrusions and formed large abnormal structures. Since these
      structures were similar to filopodia in terms of lack of MAP2 immunostaining, we
      named them "megapodia" meaning large dendritic filopodia. F-actin and PSD-95 were
      also accumulated in megapodia, and their amounts were significantly correlated
      with that of GFP-DA. However, the expression of GFP-DA did not result in the
      promotion of the morphological change from filopodia into spines. These results
      demonstrate that drebrin A accumulates spine-resident proteins via protein
      protein interaction in filopodia, and suggest that the spine formation requires
      the concurrence of the increase of drebrin-A expression and the functional
      presynaptic contact.

PMID- 16456931
TI  - Special issue in honor of Professor Marvalee Hendricks Wake.

PMID- 16456929
TI  - Disrupted Schwann cell-axon interactions in peripheral nerves of mice with
      altered L1-integrin interactions.
AB  - The cell adhesion molecule L1 is important for peripheral nerve development. Mice
      lacking the 6th Ig domain of L1 (L1-6D mice) lose L1 homophilic binding and RGD
      dependent LI-integrin binding [Itoh,K., Cheng, L., Kamei, Y., Fushiki, S.,
      Kamiguchi, H., Gutwein, P.,Stoeck, A., Arnold, B., Altevogt, P., Lemmon, V.,
      2004. Brain development in mice lacking Li-L homophilic adhesion. J. Cell
      Biol.165, 145-154]. We examined the ultrastructure of sciatic nerves from L1-6D
      at postnatal day 7 and 8 weeks. Unmyelinated axons frequently detached at the
      edge of Schwann cells, and naked axons were observed. Myelin was thinner in L1-6D
      and abnormal, multiple axons wrapped in a single myelin sheath were routinely
      observed. Previous work has shown that L1 on axons interacts with a heterophilic
      binding partner on Schwann cells to facilitate normal peripheral nerve formation.
      Taken together, it is likely that L1 on axons binds integrins on Schwann cells,
      resulting in interactions between axons and Schwann cells that are essential for
      ensheathment and myelination.

PMID- 16456932
TI  - From fundamentals to applications: recent developments in atmospheric pressure
      photoionization mass spectrometry.
AB  - Only five years after the first publication on atmospheric pressure
      photoionization (APPI), this technique has evolved rapidly as a very useful
      complement to established ionization techniques for liquid chromatography/mass
      spectrometry (LC/MS). This is reflected in a rapidly increasing number of
      publications in this field. On the one hand, thorough studies into the
      photoionization mechanism have provided deep insights into the roles and
      influences of the solvent, the dopant and other additives. On the other hand, a
      large number of new and attractive applications have recently been introduced.
      New instrumental developments have resulted in combined APPI/ESI (PAESI) and
      APPI/APCI sources and a microfabricated APPI source. In this review, the most
      important developments within the field are summarized, focusing in particular on
      the applications of the technique.

PMID- 16456933
TI  - Raman spectroscopy in astrobiology.
AB  - Raman spectroscopy is proposed as a valuable analytical technique for planetary
      exploration because it is sensitive to organic and inorganic compounds and able
      to unambiguously identify key spectral markers in a mixture of biological and
      geological components; furthermore, sample manipulation is not required and any
      size of sample can be studied without chemical or mechanical pretreatment. NASA
      and ESA are considering the adoption of miniaturised Raman spectrometers for
      inclusion in suites of analytical instrumentation to be placed on robotic landers
      on Mars in the near future to search for extinct or extant life signals. In this
      paper we review the advantages and limitations of Raman spectroscopy for the
      analysis of complex specimens with relevance to the detection of bio- and
      geomarkers in extremophilic organisms which are considered to be terrestrial
      analogues of possible extraterrestial life that could have developed on planetary
      surfaces.

PMID- 16456934
TI  - Recalling memories needs reconstruction of cortical activity.

PMID- 16456935
TI  - Low brain oestrogen linked to Alzheimer's disease risk.

PMID- 16456936
TI  - Blood-brain barrier challenged by new drug delivery vehicle.

PMID- 16456937
TI  - Treatment for glioblastoma multiforme shows promise.

PMID- 16456938
TI  - Microglial role in neuropathic pain.

PMID- 16456939
TI  - SOD1 mutant protein gets loose in ALS.

PMID- 16456940
TI  - MicroRNA in chronic lymphocytic leukemia.

PMID- 16456941
TI  - The metrics of the physician brain drain.

PMID- 16456942
TI  - The metrics of the physician brain drain.

PMID- 16456943
TI  - The metrics of the physician brain drain.

PMID- 16456944
TI  - How we know I: strange dreams. By Mole.

PMID- 16456945
TI  - Cyclooxygenase-2 expression is higher in ovarian cancer tissue adjacent to
      endometriosis than in ovarian cancer without comorbid endometriosis.
AB  - OBJECTIVES: The purpose of this study was to examine if COX-2, CK7 and CK20 are
      involved in the malignant transformation of endometriosis. METHODS: We compared
      COX-2, CK7 and CK20 expressions between isolated endometriosis lesions and
      endometriosis lesions adjacent to ovarian carcinoma and between isolated ovarian
      carcinoma and ovarian carcinoma with implants of endometriosis. Immunoreactivity
      was quantified using an immunohistochemical scoring system that corresponds to an
      image analysis-based system. RESULTS: There was no difference in COX-2, CK7 and
      CK20 expressions between the isolated endometriosis lesions and the endometriosis
      lesions adjacent to ovarian carcinoma. Similarly, CK7 and CK20 were equally
      expressed between the isolated ovarian carcinoma and the ovarian carcinoma with
      implants of endometriosis. The COX-2 over-expression rate was greater in ovarian
      carcinoma that was associated with endometriosis than in isolated ovarian
      carcinoma (27.8% versus 5.6%, P = 0.083). In endometrioid type ovarian carcinoma,
      the difference in COX-2 expression was statistically significant (50% versus 0%,
      P = 0.023). CONCLUSIONS: COX-2 over-expression may be a result of the malignant
      transformation of endometriosis to endometrioid type ovarian cancer or may
      represent an interaction between the two cellular components. With respect to
      cytokeratins, neither CK7 nor CK20 appear to be involved in the malignant
      transformation of endometriosis.

PMID- 16456946
TI  - Superlatives.

PMID- 16456947
TI  - PVRP revisions help physicians 'test the waters'.

PMID- 16456948
TI  - [Vaccination: recall or second dose, semantic difference or immunologic
      reality?].

PMID- 16456949
TI  - [Whooping cough in older children and adults].

PMID- 16456950
TI  - [Invasive Haemophilus influenzae type B infection--importance of recall].

PMID- 16456951
TI  - [Elimination of measles and congenital rubella: what vaccination strategy for the
      future?].

PMID- 16456952
TI  - Music to young ears.

PMID- 16456955
TI  - Art project reinforces HIV/AIDS education.

PMID- 16456953
TI  - HIV/AIDS and the 3 levels of prevention.

PMID- 16456954
TI  - Infectious behaviour.

PMID- 16456956
TI  - Hot topics for FAQs.

PMID- 16456957
TI  - Think globally...

PMID- 16456958
TI  - Embracing diversity, challenging inequality.

PMID- 16456959
TI  - HIV does not discriminate--do you?

PMID- 16456960
TI  - Make your Web site work!

PMID- 16456961
TI  - What you can expect at CHN.

PMID- 16456962
TI  - Council and strategy launched.

PMID- 16456963
TI  - Stigma and discrimination fuel the HIV/AIDS epidemic.

PMID- 16456964
TI  - Educational resource looks behind the pandemic.

PMID- 16456965
TI  - Canada's doing a lot...but is it soon enough?

PMID- 16456966
TI  - "How do you know what you know?".

PMID- 16456967
TI  - Canada has much to do.

PMID- 16456968
TI  - Natural helpers.

PMID- 16456969
TI  - Phase III not approved.

PMID- 16456971
TI  - Safe site still draws mixed reviews.

PMID- 16456970
TI  - Safe injection sites.

PMID- 16456972
TI  - End stigma and discrimination surrounding HIV/AIDS.

PMID- 16456973
TI  - Looking within.

PMID- 16456974
TI  - My past and future involvement with AIDS.

PMID- 16456975
TI  - The day AIDS got personal with me.

PMID- 16456976
TI  - From day one.

PMID- 16456977
TI  - Edward's lesson.

PMID- 16456978
TI  - Houston and HIV.

PMID- 16456979
TI  - One day I woke up with HIV.

PMID- 16456980
TI  - History and hope.

PMID- 16456981
TI  - Pediatric and adult HIV/AIDS treatment: still worlds apart.

PMID- 16456982
TI  - I chose not to fear.

PMID- 16456983
TI  - Being on both sides of HIV.

PMID- 16456984
TI  - How HIV affected my life.

PMID- 16456985
TI  - My American dream.

PMID- 16456986
TI  - Fractal genomics modeling: a new approach to genomic analysis and biomarker
      discovery.
AB  - Reverse engineering of genetics networks generally requires establishing
      correlative behavior within and between a very large number of genes. This
      becomes a difficult analytical problem for even a few hundred genes and the
      difficulty tends to grow exponentially as more genes are examined. Using a hybrid
      data analysis method known as Fractal Genomics Modeling (FGM), this problem is
      reduced to examining correlative behavior within small gene groups that can then
      be compared and integrated to produce a picture of larger networks using a type
      pf shotgun approach. We have applied FGM toward examining genetic networks
      involved in HIV infection in the brain. These networks have relevance both to
      processes related to HIV infection and neurodegenerative disorders. Our
      preliminary findings have produced conjectures of related pathways and networks
      as well new candidates for genetic markers in HIV brain infection. Evidence has
      also been produced which appears to show the presence of a hierarchical network
      structure within the genes studied. We will discuss the background and
      methodology of FGM as well as our recent findings.

PMID- 16456987
TI  - [Croatian Consensus Conference on Viral Hepatitis. December 2005. Zagreb].

PMID- 16456988
TI  - Clostridium difficile epidemic strain far reaching.

PMID- 16456989
TI  - China set to double annual spending on HIV/AIDS.

PMID- 16456990
TI  - Medical journal criticizes Merck over Vioxx data.

PMID- 16456991
TI  - Diabetes: It is all about the numbers.

PMID- 16456992
TI  - Access to prevention.

PMID- 16456993
TI  - Reporting product defects.

PMID- 16456994
TI  - Dental radiography.

PMID- 16456995
TI  - More about radiography.

PMID- 16456996
TI  - Do portfolio assessments have a place in dental licensure? Against the
      proposition.

PMID- 16456997
TI  - Do portfolio assessments have a place in dental licensure? For the proposition.

PMID- 16456998
TI  - Meta-analysis of immediate changes with rapid maxillary expansion treatment.
AB  - BACKGROUND: The authors conducted a literature review to evaluate immediate
      transverse, anteroposterior, and vertical dental and skeletal changes produced by
      rapid maxillary expansion (RME). TYPES OF STUDIES REVIEWED: The authors reviewed
      clinical trials that assessed immediate dental and/or skeletal changes after RME
      using cephalometric analysis, model casts or both. No surgical or other
      simultaneous treatment was accepted during the evaluation period. RESULTS: The
      authors searched electronic databases and found 31 articles that met the initial
      inclusion criteria. The authors later rejected 12 of these articles because they
      did not report immediate changes, three because they lacked detailed descriptions
      of their results and two because of their nonconventional appliance designs.
      Fourteen articles satisfied th final inclusion criteria; however, they had
      methodological deficiencies. CLINICAL IMPLICATIONS: The greatest changes
      resulting from RME in the studies analyzed were dental and skeletal transverse
      changes. Few vertical and anteroposterior immediate changes were statistically
      significant, though they probably are not clinically important.

PMID- 16456999
TI  - Diagnosis of systemic sarcoidosis prompted by orofacial manifestations: a review
      of the literature.
AB  - BACKGROUND: Sarcoidosis is a multifactorial systemic inflammatory disorder of
      unknown origin characterized by many potential signs and symptoms, as well as by
      the presence of noncaseating granulomas in the organs involved. Sarcoidosis also
      may manifest in the oral and maxillofacial region. CASE DESCRIPTION: The authors
      describe a patient with xerostomia, dysgeusia, oral burning, xerophthalmia and
      bilateral parotid enlargement. She was diagnosed as having systemic sarcoidosis
      on the basis of the histologic findings of a biopsy of the labial minor salivary
      gland, as well as subsequent diagnostic evalutons. CONCLUSION AND CLINICAL
      IMPLICATIONS: Enlargement of major salivary glands may be the first sign of
      sarcoidosis in a patient with few other symptoms or clinical findings suggestive
      of the disease. This case emphasizes the importance of including sarcoidosis in
      the differential diagnosis of bilateral parotid swelling associated with
      xerostomia. It also highlights the dentist's potential role in the diagnosis and
      dental treatment of patients with systemic sarcoidosis.

PMID- 16457000
TI  - Odontogenic signs and symptoms as predictors of odontogenic infection: a clinical
      trial.
AB  - BACKGROUND: The authors conducted a study to determine if odontogenic signs and
      symptoms in the emergency department predicted the development of overt
      odontogenic infection at a follow-up dental visit. METHODS: One hundred ninety
      five patients with odontalgia, but without overt signs of infection, were
      enrolled in a prospective, double-blind, randomized clinical trial. Data included
      dental diagnosis, pain characteristics, presence of caries and restorations,
      presence and size of periapical radiolucencies and other diagnostic test results.
      RESULTS: Thirteen of 134 subjects for whom data were available had signs of
      infection at the follow-up visit. Subjects in the follow-up infected (FU-I) group
      had larger baseline radiolucencies than did subjects in the follow-up noninfected
      (FU-NI) group, and restorations were more prevalent for involved teeth in the FU
      I group than in the FU-NI group. CONCLUSIONS: A relationship exists between
      radiolucency size and the presence of amalgam restorations in patients who
      develop clinical signs of infection. Penicillin did not appear to influence this
      progression. CLINICAL IMPLICATIONS: Antibiotics are not effective in preventing
      the development of odontogenic infection when definitive dental therapy cannot be
      provided for acute pain in the absence of clinical signs of infection. Although
      the overall risk of developing infection is low, early treatment is indicated for
      teeth with larger periapical radiolucencies, amalgam restorations or both.

PMID- 16457001
TI  - Inability of laser and rotary instrumentation to eliminate root canal infection.
AB  - BACKGROUND: The authors evaluated the antibacterial effectiveness of laser
      instrumentation and rotary instrumentation of anterior, single-rooted teeth
      infected with Enterococcus faecalis. METHODS: The authors divided 35 infected
      samples into five groups: Group A: inoculation, laser, 17 percent ethylene
      diamine-tetra-acetate (EDTA), 2.5 percent sodium hypochlorite (NaOCl) (n=10);
      Group B: inoculation, laser, 17 percent EDTA, sterile saline (n = 10); Group C:
      inoculation, rotary, 17 percent EDTA, 2.5 percent NaOCl (n=10); Group D:
      inoculation, no instrumentation (positive control) (n=5); Group E: no
      inoculation, no instrumentation (negative control) (n=5). They sampled and
      incubated dentin shavings from each canal for bacterial growth. RESULTS: In Group
      A, eight tubes were positive for bacterial growth. In Group B, 10 tubes were
      positive for bacterial growth. In Group C, six tube were positive for bacterial
      growth. In Group D, all of the tubes were positive for bacterial growth. In Group
      E, no tubes showed bacterial growth. The Fisher exact test showed no significant
      differences among groups A, E and C. CONCLUSION: Neither the laser nor the rotary
      instrumentation was able to eliminate endodontic infection. CLINICAL
      IMPLICATIONS: Although lasers have been presented as high-tech tools for
      disinfecting root canals, the laser was ineffective in this study.

PMID- 16457003
TI  - Opening a new office: the dentist's personal frontier.
AB  - BACKGROUND: The purpose of this article is to assist the dental practitioner by
      providing insight into commercial real estate and a framework for identifying and
      securing new office space, as well as by addressing concerns about the physical
      space of a dental practice. CONCLUSIONS: In the process of identifying and
      securing new office space, the dental practitioner can maximize efficiency and
      minimize risk by assembling a team of professionals to assist him or her. This
      team should be composed of an accountant and an attorney, as well as a dental
      equipment/design specialist and a commercial real estate professional. PRACTICE
      IMPLICATIONS: The professional team will provide invaluable assistance to the
      dentist, enabling him or her to avoid major financial, legal, logistic and real
      estate-related pitfalls inherent in establishing or moving a dental practice.

PMID- 16457002
TI  - Clinical performance evaluation of a packable posterior composite in bulk-cured
      restorations.
AB  - BACKGROUND: The authors evaluated the clinical performance of Prodigy Condensable
      (Kerr, Orange, Calif.) composite placed and cured in increments up to 5
      millimeters thick. METHODS: The authors placed 57 Class II restorations in 32
      patients in composite increments up to 5 mm thick. Using this technique, they
      placed the majority of restorations in one increment and then carved the occlusal
      and proximal anatomy before light curing. The authors evaluated the restorations
      at three, six, 12, 24 and 36 months. RESULTS: No restorations required
      replacement; however, 11 developed a defect requiring repair or continued
      observation. Of these 11, nine restorations developed defects on the margins of
      the restorations and two developed secondary caries. The Kaplan-Meier estimate of
      probability that a restoration would develop a defect during 36 months that would
      require immediate repair was 0.13. Postoperative sensitivity was not
      significantly different from preoperative sensitivity. CONCLUSIONS: The authors
      found that no restorations required replacement and no increased postoperative
      sensitivity occurred. CLINICAL IMPLICATIONS: The authors suggest that this
      composite material can be placed in a single increment up to 5 mm thick for Class
      II restorations.

PMID- 16457005
TI  - Making fixed prostheses that are not too high.
AB  - It has been observed that a high percentage of multiple crowns or FPDs arrive
      from laboratories too "high." This article suggests methods to create accurate
      alginate impressions, opposing casts and IORs. If dentists use these techniques,
      it is anticipated that fewer FPDs will be too high as dentists attempt to seat
      them in the mouth.

PMID- 16457004
TI  - Early orthodontic treatment as a means to increase access for children enrolled
      in Medicaid in Washington state.
AB  - BACKGROUND: The authors assessed the likelihood that interceptive orthodontic
      Medicaid programs would increase access to care for Washington children. METHODS:
      The authors surveyed 210 Washington state orthodontists, including questions on
      demographics, attitudes toward early treatment, use of innovations and
      perceptions of Medicaid. Respondents were either Medicaid participants or
      nonparticipants. RESULTS: Fifty of 159 respondents were Medicaid participants.
      Most respondents perceived early orthodontic treatment as beneficial. Medicaid
      participants were more willing to participate in Medicaid early-treatment
      programs, had slightly fewer patients in the "other insurance" category, provided
      more discounted fees, received more Medicaid inquiries, practiced in rural areas
      with lower household incomes, reported feeling overworked and experienced fewer
      Medicaid problems. The principal problem reported with the Medicaid system was
      low fee reimbursement. CONCLUSIONS: Programs offering early orthodontic treatment
      could increase access. Important barriers would be low fees and unfamiliarity
      with Medicaid. PRACTICE IMPLICATIONS: Medicaid should design programs aimed at
      early treatment with reasonable reimbursement and an educational component.

PMID- 16457006
TI  - Dealing with dental insurance.
AB  - Dental insurance companies can have many different policies, with varying
      requirements depending on the company. This requires a tremendous amount of time
      on the part of dentists and their office teams to communicate with insurance
      companies, file all the proper data, acquire predetermination information when
      required and address a myriad of other factors. By managing this process
      carefully, practices can save time and labor expenses, especially if patients are
      well-educated regarding what their dental insurance covers and what it does not.

PMID- 16457007
TI  - Informed consent: how performing a less invasive procedure led to claim of
      battery.

PMID- 16457008
TI  - Am I living up to my ethical responsibilities as a dentist?

PMID- 16457009
TI  - For the dental patient. Tooth eruption: the permanent teeth.

PMID- 16457010
TI  - New frontiers for rare pulmonary diseases.
AB  - This Issue of Sarcoidosis Vasculitis and Diffuse Lung Diseases is dedicated to a
      special event which was held in Milan in February 2005. The First International
      Conference on Rare Pulmonary Diseases and Orphan Drugs in Respiratory Medicine
      brought together for two days most of the leading world authorities in the field
      of interstitial lung diseases. Over 200 investigators from 9 different countries
      convened to assess current knowledge in the field of pathogenesis, diagnosis and
      therapy of rare lung disorders. An incredible amount of data was discussed during
      the meeting, testifying to the recent advances in the clinical management of
      these diseases.

PMID- 16457011
TI  - The Italian register for diffuse infiltrative lung disorders (RIPID): a four-year
      report.
AB  - INTRODUCTION: RIPID (Italian register for diffuse infiltrative lung disorders) is
      a register aimed to create a national database of diffuse infiltrative lung
      disorders, also known as interstitial lung diseases. MATERIAL AND METHODS: The
      RIPID register collected prevalent data on patients affected by infiltrative
      diffuse lung disorders. The data form contains socio-demographic information
      (sex, age, years of education), existence in life, smoking habits, clinical data,
      diagnostic procedures (chest high resolution computed tomography (HRCT),
      bronchoalveolar lavage (BAL), transbronchial biopsies (TBB), surgical biopsies)
      and respiratory function tests at the time of diagnosis. RESULTS: Up to
      18/01/2005 a total of 3152 patients had been included in the register. Seventy
      nine centers and 138 physicians in all 20 regions of Italy contributed to patient
      enrolment. The vast majority of cases were from Northern Italy (2343 cases, 75%).
      The most frequently reported diagnoses were Sarcoidosis (1063 patients) and
      Idiopathic Pulmonary Fibrosis (IPF, 864 patients). DISCUSSION: The data in the
      RIPID confirm that epidemiological registries can be useful tools to investigate
      rare or relatively rare disorders (e.g. Sarcoidosis and IPF), in order to design
      multicentric clinical studies of adequate sample size, aimed at providing
      standardized diagnostic, management and follow up criteria with a particular
      regard to outcome.

PMID- 16457012
TI  - Cytokines, chemokines and other biomolecular markers in sarcoidosis.
AB  - In recent years our knowledge in terms of the network of interactions between
      immunocompetent cells that set the stage for the pathogenesis of sarcoidosis has
      continuously improved. Remarkable advances have been made in understanding
      general immunological and molecular aspects of the mechanisms leading to
      granuloma formation. In this manuscript we will review the current concepts on
      cellular interactions which define regulatory networks ultimately contributing to
      the granuloma formation at sites of disease activity in sarcoidosis. The
      biological effects of Th1 and Th2 cytokines in sarcoid lung will be taken into
      account and the importance of the local production of those chemokines and
      cytokines whose release has been recently demonstrated within the lung of
      patients with sarcoidosis will be emphasized.

PMID- 16457013
TI  - Idiopathic interstitial pneumonias: Primum movens: epithelial, endothelial or
      whatever.
AB  - The pathogenesis of idiopathic interstitial pneumonias (IIPs), particularly of
      idiopathic pulmonary fibrosis (IPF), is still unknown and the precise nature of
      the primum movens is strongly debated. Epithelial cells can be the first target
      of various environmental toxic agents. Both types of pneumocytes may be injured.
      Type I pneumocyte loss, however, is most conspicuous in fibroblastic foci, the
      principal sites where irreversible fibrogenesis starts. Epithelial regeneration
      is highly disturbed: cuboidal and bronchial cells are mainly involved in alveolar
      repair. These cells, unable to accomplish important functions of normal
      pneumocytes, secrete various factors inducing migration and proliferation of
      fibroblasts responsible for progressive extracellular matrix accumulation and
      lung remodelling. Endothelial cells may also be considered the major players in
      the initiation of fibrogenic events. Microvascular injury has been largely
      demonstrated as an early event in IPF lungs. Thrombin as well as other
      coagulation products has many biological effects such as the activation of
      different profibrotic factors, which in addition to other fibrogenetic molecules
      released by stimulated endothelium, are responsible for migration and
      proliferation of fibroblasts. The old pathogenesis of IPF: chronic inflammation
      can now be considered the principal event in other non IPF-IIPs. Among
      inflammatory cells, different cell types have been extensively suggested to play
      a key role in the pathogenesis of pulmonary fibrosis: granulocytes and
      eosinophils or mast cells. More recently novel mechanisms underlying the
      pathogenesis of pulmonary fibrosis have been proposed: bone marrow-derived stem
      cells may play a crucial role in the fibroproliferative response as well as in
      epithelial regeneration.

PMID- 16457014
TI  - Which prognostic indicator should we use for clinical practice in the initial
      evaluation and follow-up of IIP: should we depend on PFT, HRCT or...what?
AB  - Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and
      fibrotic disorders of the lung parenchyma that cause restrictive physiology and
      impair gas exchange. Usual interstitial pneumonia and non-specific interstitial
      pneumonia comprise the majority of idiopathic interstitial pneumonia cases.
      Previous studies have identified the histopathologic pattern as the most
      important baseline factor in determining prognosis. The non-invasive diagnosis of
      these diseases is sometimes uncertain but histological evaluation is an imperfect
      gold-standard. In some cases, the biopsy specimen may not be representative of
      the entire lung. In other cases, there may be differences in interpretation of
      the histological findings. HRCT has also assumed a greater role in the diagnosis
      and management of patients with idiopathic interstitial pneumonia. Factors
      affecting prognosis are discussed controversially. Histological criteria,
      clinical features, or lung function parameters are not clear prognostic
      indicators. Increased interstitial abnormalities in the HRCT, parameters
      indicating restrictive lung function, desaturation at 6MWT and abnormal gas
      exchange are possible determinants of survival. The prognostic value of pulmonary
      function trends over time may prove more useful. Longitudinal behavior is a more
      accurate determinant of outcome than evaluation at a single point in time. It is
      important to remember that no predictor of survival can ever reliably predict an
      individual patient's prognosis. Physicians should realize this limitation, and
      use predictor tools as general prognostic guides, not crystal balls. However, due
      to the great variability in the natural history of the disease, close monitoring
      of the patients may be necessary to evaluate the individual course of each
      patient.

PMID- 16457015
TI  - An integrated clinical approach to diffuse cystic lung diseases.
AB  - Lymphangioleiomyomatosis and Langerhans cell Histiocytosis are two different
      diseases that can involve the lungs, with unknown etiology and origin. Both are
      rare, present a similar radiological pattern (multiple nodules and cysts in the
      lungs) and may have a similar clinical presentation, with progressive dyspnea,
      hemoptysis, pneumothorax and a variable course usually culminating in respiratory
      failure. Due to these similarities a differential diagnosis may be difficult in
      some instances. This review underlines differences in epidemiology, pathogenesis
      and prognosis that could assist clinicians in making a differential diagnosis of
      these rare and severe pulmonary diseases.

PMID- 16457016
TI  - Respiratory system involvement in ANCA-associated systemic vasculitides.
AB  - BACKGROUND AND AIM OF THE WORK: The respiratory system may be involved in all
      systemic vasculitides (SV), although with a variable frequency. Lung disease is a
      very common and important feature of the antineutrophil cytoplasmic antibodies
      (ANCA)-associated SV (AASV), such as Wegener's granulomatosis (WG), Churg-Strauss
      syndrome (CSS), and microscopic polyangiitis (MPA). The aim of the work is to
      review the clinical findings, as well as the radiological and pathological
      features of respiratory system involvement in AASV. METHODS: A detailed search
      via the PubMed index from the National Library of Medicine, covering the period
      from 1980 to December 2004, was accomplished. RESULTS: In WG, almost all patients
      have either upper airway or lower respiratory tract disease. Solitary or multiple
      nodules and masses are the most common findings on chest radiograph. Asthma is a
      main symptom of CSS, often preceded by allergic rhinitis, frequently complicated
      by nasal polyposis and sinusitis. Pulmonary transient and patchy alveolar
      infiltrates are the most common radiographic findings. In MPA, diffuse alveolar
      haemorrhage (DAH) due to alveolar capillaritis is the most frequent manifestation
      of the respiratory involvement, clinically expressing with haemoptysis,
      respiratory distress and anaemia. CONCLUSIONS: The involvement of the respiratory
      system is a very common and important feature of AASV. There is substantial
      overlap in many of the clinical pulmonary features of AASV. In some cases,
      distinguishing between these diseases on the basis of the clinical features alone
      is difficult and pathological assessment is needed.

PMID- 16457017
TI  - Clinical and molecular insights into lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease of women that is characterized
      by a proliferation of abnormal smooth muscle-like cells (LAM cells), which leads
      to cystic lung lesions, lymphatic abnormalities, and abdominal tumors (e.g.,
      angiomyolipomas). LAM occurs sporadically or in association with tuberous
      sclerosis complex, an autosomal dominant syndrome characterized by hamartoma-like
      tumor growths. The tumor suppressor genes TSC1 and TSC2 have been implicated in
      the etiology of LAM, as mutations and loss of heterozygosity (LOH) in TSC2 have
      been detected in LAM cells. TSC1 encodes hamartin, with a postulated role in
      actin cytoskeleton reorganization. TSC2 encodes tuberin, a protein with roles in
      cell growth and proliferation, transcriptional activation, and endocytosis. LAM
      cells, as defined by TSC2 LOH, have been detected in blood and body fluids, and
      can metastasize. LAM presents insidiously with progressive breathlessness, or
      dramatically with recurrent pneumothorax, chylothorax, or sudden abdominal
      hemorrhage. CT scans show numerous thin-walled cysts throughout the lungs,
      abdominal angiomyolipomas, and lymphangioleiomyomas. Pulmonary function tests
      show reduced flow rates (FEV1) and diffusion capacity (DL(CO)). Twenty per cent
      of patients have positive bronchodilator responses. Exercise testing shows gas
      exchange abnormalities, ventilatory limitation, and hypoxemia that may occur with
      near-normal lung function. Progression of disease is best assessed by
      measurements of DL(CO) and FEV1. In the proper clinical setting, LAM may be
      diagnosed by a thoraco-abdominal CT scan. Tissue biopsy with special stains (HMB
      45) should be reserved for cases with atypical presentations. There is no
      effective treatment for LAM, but on-going therapeutic trials with rapamycin
      appear promising.

PMID- 16457018
TI  - Pulmonary alveolar proteinosis: a new autoimmune disease.
AB  - Pulmonary alveolar proteinosis is a rare disorder characterised by abundant
      accumulation of surfactant-derived phospholipids and protein components in the
      alveoli and distal airways. In this review we focus the discussion on acquired
      (idiopathic or primary) alveolar proteinosis. We report the studies that
      developed the concept that this disorder is an autoimmune disease caused by auto
      antibodies against GM-CSF. The clinical management of the patients is also
      described.

PMID- 16457019
TI  - Steroid and/or other immunosuppressive therapies in idiopathic interstitial
      pneumonias: have they still a role?
AB  - The idiopathic interstitial pneumonias (IIPs) comprise a number of clinico
      pathological entities of unknown origin, which are sufficiently different from
      one another to be designated as separate disease entities. The aim of this review
      is to describe the level of evidence available on the efficacy of corticosteroids
      and immunosuppressive, antifibrotic, or immunomodulatory therapies in the
      treatment of different IIPs.

PMID- 16457020
TI  - Lung transplantation for rare pulmonary diseases.
AB  - Emphysema, idiopathic pulmonary fibrosis and cystic fibrosis are the major
      indications for lung transplantation. This article will present an overview of
      lung transplantation in the context of rare pulmonary diseases, in particular
      pulmonary sarcoidosis, lymphangioleiomyomatosis (LAM), and pulmonary Langerhans
      Cell Histiocytosis X (LCH). It will present criteria used in deciding when a
      patient should be referred and will discuss medical management in the context of
      lung transplantation.

PMID- 16457021
TI  - Idiopathic pulmonary hypertension: what did we learn from genes?
AB  - Pulmonary arterial hypertension (PAH) is an uncommon disorder. PAH can be
      idiopathic, associated with other conditions or clustered in families. Indeed, at
      least 6% of individuals diagnosed with so-called "primary" pulmonary hypertension
      have a family history of the disorder. Familial PAH segregates as an autosomal
      dominant trait but with markedly reduced penetrance. Defects within bone
      morphogenetic protein receptor type II gene (BMPR2), coding for a type II
      receptor member of the transforming growth factor beta (TGF-beta) family, have
      been shown to underlie familial PAH. Germline BMPR2 mutations have been detected
      in at least 60% of the families studied to date. Disease-associated mutations are
      predicted to interrupt the BMP-mediated signalling pathway predisposing to
      proliferation of cells within small pulmonary arteries. Several lines of evidence
      point to the potential requirement of additional factors, either environmental or
      genetic, in the pathogenesis of the disease. In addition, a proportion of
      idiopathic PAH as well as anorexigen-associated PAH turn out to have an inherited
      basis, as demonstrated by detection of germline BMPR2 mutations. Analysis of
      other genes encoding TGF-beta receptor proteins, led to the demonstration that
      PAH in association with hereditary hemorrhagic telangiectasia, an autosomal
      dominant vascular dysplasia, can involve other TGF-beta receptor subtypes. These
      observations support the hypothesis that mutations in the TGF-beta superfamily
      may be a trigger for pulmonary vascular remodeling. Nevertheless, PAH
      pathobiology remains unclear and genomic approaches may identify additional
      molecular determinants for this disorder.

PMID- 16457022
TI  - Key developments in women's health.

PMID- 16457023
TI  - Caring for women seeking abortion.

PMID- 16457024
TI  - Casebook: menorrhagia.

PMID- 16457025
TI  - Preparing for the oral exam.

PMID- 16457027
TI  - [Patient education: a therapeutic concept that has become essential in
      cardiology].

PMID- 16457028
TI  - [Main issues and contributions of the evaluation of health care networks].
AB  - Health care networks correspond to a form of horizontal and flexible
      organisation, which consists in dealing with complex problems of health and long
      term care. Networks rest entirely on the mechanisms of coordination between the
      various actors of care, whose keystone is the medical information flow. The
      challenge of the health networks evaluation is to prove the added value of a
      network organization, instead of a conventional disease-centred health care. The
      evaluation of health care networks is legally required but not sustained by
      specialists. Evaluation must ensure the existence of a real management; measure
      the interest of health care professionals and the impact of the network on
      professional practices. Moreover, evaluation accompanies the development of the
      network and offers the advisability to the decision maker of obtaining a tool for
      control of management, i.e. an information tool and a decision-making help, with
      the aim of a continuous improvement of the quality of care. However the absence
      of formation of the medical coordinators to management, makes networks management
      problematic. Thus, health care networks cannot make the saving in a good
      administrative and management base. In the same way health care networks must
      obtain an information system adapted to their type of coordination, allowing the
      evaluation required by the financier.

PMID- 16457029
TI  - High risk hypertensives: pre-hospital management of acute myocardial infarction-
      results from the French nationwide registry USIC 2000.
AB  - OBJECTIVE: To assess the use of mobile coronary care units (MCU) in hypertensive
      patients previously treated for cardiovascular diseases in comparison with those
      with no history of cardiovascular disease and to estimate the influence of the
      use of MCU on cardiovascular outcome in this population. PATIENTS: We used a
      nationwide prospective registry of all patients admitted for AMI in French
      intensive care units in 2000. Patients without history of hypertension or
      patients admitted with pulmonary oedema or cardiogenic shock were excluded. Men
      (N = 514) and women (N = 291) were analysed separately. RESULTS: The proportion
      of patients with history of myocardial infarction, peripheral artery disease and
      stroke was not significantly higher in subjects who used physician-staffed MCU as
      compared with patients with no history of myocardial infarction, peripheral
      artery disease or stroke. In each sex, revascularization (pre hospital
      fibrinolysis, in hospital fibrinolysis or coronary angioplasty) were more
      frequent in patients who used MCU. Also, one year cardiovascular mortality was
      lower in men who used MCU. CONCLUSION: Known high risk hypertensive patients did
      not use physician-staffed MCU more than subjects free of such condition.
      Education of hypertensive patients at risk during routine visits is required to
      increase of the use of physician-staffed MCU in case of symptoms suggestive of
      AMI.

PMID- 16457030
TI  - [Importance of therapeutic education in the multidisciplinary management of heart
      failure].
AB  - Heart failure is a severe disease with high morbidity and mortality rates. The
      interest for multidisciplinary heart failure patient management is increasing in
      order to improve prescription of medical therapies and to allow a better quality
      of life. Proofs of reduction in morbi-mortality exist and some models of
      management have been assessed. The most important point remains the major role of
      therapeutic education. Training of health care professionals is needed. Tools for
      therapeutic education have been created and can be associated with complementary
      informative means. All these elements allow that a new approach of heart failure
      takes in place in France.

PMID- 16457032
TI  - [The anticoagulation clinic: that can not be ignored].
AB  - Complications linked to drug absorption are most frequently observed in the case
      of treatment by vitamin K antagonist (VKA), whereas 1% of the French population
      is treated by VKA. Despite official recommendations renewal, these complications
      are not decreasing. The experience of anticoagulation clinics (AC) in other
      countries proves their efficiency in the reduction of two-thirds of hemorragies
      and thrombotic recurrences. The concept of AC strictly obliged to associate
      therapeutic education to the patient and the calculation of the treatment dosage.
      Our experience started in 1998. We suggest a patient education at first during an
      individual consultation then during a group session. A multicentric prospective
      evaluation of AC vs. the conventional follow-up is on the way in France having as
      objectives to test the clinical efficiency and the comparison of the cost for
      such a supervision. In any case, important efforts have to be accomplished
      regarding the support of present and future antithrombotics. Their complexity of
      indications, supervision, and tolerance has to reinforce the rigour of
      therapeutic steps from the prescription to the absorption of the drug, with the
      possibility to appeal to the AC.

PMID- 16457031
TI  - [Role of cardiologists in control of risk factors and prescription of secondary
      preventive drugs in elderly patients with atherosclerotic cardiovascular disease.
      The French ELIAGE-MG survey].
AB  - Little information is available as regards risk factor control and use of
      secondary prevention medications in elderly populations with documented
      atherosclerotic disease. The ELIAGE-MG survey included 3247 patients with
      cardiovascular disease seen in ambulatory practice. Overall, both the control of
      risk factors and the use of secondary prevention medications was suboptimal in
      these patients. However, those having consulted a cardiologist at any time during
      the previous year had better control of risk factors (and particularly LDL
      cholesterol and smoking) and were more often prescribed recommended secondary
      prevention medications.

PMID- 16457033
TI  - [Patient education and patient at risk. A new approach in cardiology].
AB  - For more than 10 years, preventive cardiology has obtained many positive results.
      Cardiologists can alter the prognosis of cardiovascular disease in primary and
      secondary prevention. In primary prevention or during the chronic phases of
      coronary artery disease, prevention is mainly based on drugs. However, prevention
      can be achieved only if patients have a good understanding of their disease, fair
      relationships with their physicians and a strict compliance with their
      treatments. Patient education is useful for the patient in order to control
      cardiovascular risk. In France, the PEGASE program evaluates the efficacy of an
      educational program in high risk patients. The final objective of this program is
      to spread this educational program for high risk patients to cardiologists all
      over the country.

PMID- 16457035
TI  - [Factors associated with early invasive strategy in patients with acute coronary
      syndrome. A multicenter study].
AB  - OBJECTIVES: To identify the factors associated with early cardiac catheterization
      in patients with a non ST-segment elevation acute coronary syndrome. METHODS: We
      analyzed data collected by retrospective chart review for 208 patients presenting
      at seven French hospitals with an acute coronary syndrome (chest pain at rest
      within 24 h prior to presentation with positive cardiac markers and/or
      electrocardiographic changes) between January and March 2005. RESULTS: Eighty
      seven patients (42%) were first admitted to hospitals with cardiac
      catheterization facilities. One hundred ten patients (53%, 95% confidence
      interval [95% CI], 46-60) underwent early cardiac catheterization less than 48 h
      following presentation. In addition to presentation at hospitals with
      catheterization facilities, factors independently associated with early
      catheterization included positive cardiac markers in patients first admitted to
      hospitals without catheterization facilities (adjusted odds ratio [aOR] 34.5, 95%
      CI, 4.4-268.0) and diabetes mellitus (aOR, 0.4, 95%CI, 0.2-0.9). With the
      exception of positive cardiac markers, no risk factors comprising the TIMI risk
      score were associated with increased odds of early cardiac catheterization.
      During the index hospital stay, six patients (3%) died, seven patients (3%) had
      pulmonary edema, three patients (1%) had major or minor bleeding, and none had ST
      segment elevation myocardial infarction. CONCLUSION: Despite the dissemination of
      international guidelines, the use of early cardiac catheterization remains
      related to initial presentation at hospitals with catheterization facilities
      rather than risk assessment in patients with a non ST-segment elevation acute
      coronary syndrome.

PMID- 16457034
TI  - [Evaluation of a multidisciplinary management by a health care network for
      patients with chronic heart failure].
AB  - OBJECTIVES: To evaluate the impact, at three months, of a multidisciplinary
      management by a health care network for patients with chronic heart failure,
      compared with a historic control group. METHODS: We carried out an exhaustive
      prospective investigation of 68 patients included in the network in 2001 (stage
      II to IV of NYHA classification). The historic control was 64 patients
      hospitalized in 2000 with the same inclusion criteria. RESULTS: Mean age (78
      years) and the initial severity of heart failure (stage NYHA II: 43%, III: 55%,
      IV: 2%) did not differ between the two groups. Seven parameters significantly
      improved at three months in intervention group: systolic blood pressure, heart
      frequency, walking distance covered in six minutes, quality of life score,
      prescription of angiotensin converting enzyme inhibitor at maximal dose,
      prescription of beta-blocker and the patient's compliance with therapy. The three
      months survival without event (hospital readmission or death) did not
      significantly differ between the two groups: 45% [33-57] in 2000 versus 41% [29
      53] in 2001. CONCLUSION: The functional status and treatments of the patients
      significantly improved three months after their inclusion in health care network.
      The impact of the health care network for chronic heart failure management should
      be studied by randomised trials.

PMID- 16457036
TI  - [Cardiac myxoma. Surgical treatment. About 20 cases].
AB  - INTRODUCTION: Cardiac myxoma is the commune cardiac tumors. Their clinical status
      depends in the anatomic type. The aim of this study is to evaluate our results
      and to compare them for literature. PATIENTS AND METHODS: From January 1990 to
      June 2004, 20 patients (8 males and 12 females) with mean age of 49 years
      underwent surgical treatment of cardiac myxoma. The tumors were in left atrium in
      14 cases, in right atrium in 4 cases and biatrial in 2 cases. Surgical treatment
      consisted in complete resection of the tumor in all cases associated with partial
      atrial septal resection in 9 cases. RESULTS: There is not death in the
      postoperative outcome. The mean follow up is 50 months. The late mortality rate
      was 10%. All patients are asymptomatic and the echocardiography control showed no
      tumor recurrence. CONCLUSION: Cardiac myxoma is the communist primary tumor of
      the heart. Diagnosis is based upon echocardiography. Surgical management has well
      out come with low morbidity and mortality. Late results are satisfactory but
      regular screening is recommended although risk of recurrence is low.

PMID- 16457037
TI  - [Massive pulmonary embolism and stroke due to thrombus across the foramen ovale].
AB  - We report the case of a man admitted for massive pulmonary embolism.
      Transthoracic echocardiography showed a serpentine thrombus in the right atrium
      across the foramen oval. Because of an acute worsening of the circulatory
      insufficiency, an intravenous thrombolysis was prescribed and the patient
      recovered progressively. An early control echocardiography showed the
      disappearing of the intracardiac thrombus and no evidence of abnormality of
      interatrial septum. While there was no evidence of venous thrombosis in legs, a
      renal cancer was diagnosed by echography. Silent stroke were highlighted at the
      scanner. This clinical case leads to discuss the origin of thrombus (in situ
      formation or thrombus migration) as well as the treatment (heparinotherapy,
      thrombolysis, surgical embolectomy, definitive closure of the foramen oval).

PMID- 16457039
TI  - Changes in ascorbic acid and malondialdehyde in rats after exposure to mercury.
AB  - BACKGROUND: Mercury is one of the ubiquitous pollutants participating in
      generation of reactive oxygen species leading to the formation of oxidative
      stress. METHODS: Changes in plasma concentrations of ascorbic acid and
      malondialdehyde were measured in rats after per os exposure to different doses of
      mercury (as mercuric chloride) for 30 d. RESULTS: The production of ascorbic acid
      and malondialdehyde was related to the dosage of mercuric chloride. Within the
      group of rats receiving mercuric chloride in the concentration of 10 micromol/L
      (corresponding to the LD50 of HgCl2), the concentrations of ascorbic acid and
      malondialdehyde were increased by 22.19 % and by 6.88 % respectively when
      compared with the control group. The doses of mercuric chloride lower than LD50
      reduced the production of ascorbic acid and malondialdehyde statistically.
      CONCLUSIONS: Mercury is one of the inducers of oxidative stress in plasma of
      rats. The oxidation damage caused by mercuric chloride is proven by increased
      malondialdehyde formation and subsequently compensated by an overproduction of
      ascorbic acid (Tab. 3, Ref. 22).

PMID- 16457038
TI  - Inhibition of guanylyl cyclase in the airways hyperreactivity.
AB  - BACKGROUND: The majority of nitric oxide (NO) effects in the respiratory system
      are mediated via the stimulation of soluble guanylyl cyclase with subsequent
      generation of the second messenger--cyclic guanosine monophosphate (cGMP).
      OBJECTIVES: We were interested in the effect of non-selective soluble guanylyl
      cyclase inhibitor--methylene blue on the exogenous irritant-induced bronchial
      hyperreactivity. METHODS: Male guinea pigs were used in the experiment. The
      animals received non-selective soluble guanylyl cyclase inhibitor--methylene blue
      in a dose of 50 or 100 mg/kg b.w. 30 minutes before inhalation of the exogenous
      irritant--toluene vapours. The toluene exposition lasted three consecutive days
      during two hours in in vivo conditions. The monitoring of tracheal and lung
      tissue strips reactivity changes was carried out in in vitro conditions. The
      brochoconstrictor mediators histamine and acetylcholine in the cumulative doses
      (10(-8)-10(-3) mol/l) were used in the experiment. RESULTS: The methylene blue
      pretreatment induced the decrease of tracheal and lung tissue smooth muscle
      contraction amplitude increased by exogenous irritant--toluene. We recorded
      different smooth muscle response depending on the doses of inhibitor. Methylene
      blue in a dose of 50 mg/kg b.w. affected mainly tracheal smooth muscle, in a dose
      of 100 mg/kg b.w. mainly the lung tissue. CONCLUSION: The interaction between
      nitric oxide and soluble guanylyl cyclase can be important for bronchial
      reactivity changes. The changes depended on the dose of inhibitor and on the type
      of respiratory system tissue (trachea, lung). We can summarise that changes of
      the airways reactivity are not only evoked by NO/cGMP pathway but probably by any
      other mechanisms (Fig. 5, Ref. 26).

PMID- 16457040
TI  - Nitric oxide modulation of metabolic and haemodynamic balance.
AB  - Nitric oxide (NO) belongs to signal molecules and modulates notably rapid and
      dynamic processes. Interests are focused on the decreased NO synthesis by
      endothelial and mitochondrial nitric oxide synthases with the metabolic (i.e.
      insulin resistance, diabetes, energetical dysbalance) and vascular (i.e.
      hypertension, atheroslerosis) consequences. A significant source of NO are NO
      donors (i.e. organic nitrates). A number of antihypertensive drugs stimulates NO
      production or inhibits the production of its antagonists (angiotensin II,
      catecholamines), other drugs (i.e. glucocorticoids) inhibit NO production. These
      interferences are targets of an intensive research with the aim of NO dysbalance
      prevention, hypertension and metabolic dysbalances correction. While the clinical
      research concentrates on NO and insulin resistance, the molecular biological
      research concentrates on "mitochondrial medicine" with the ambition to formulate
      a new theory of aging, carcinoma, and other fundamental biological processes
      (Fig. 1, Ref. 47).

PMID- 16457041
TI  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia.
AB  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a
      progressive disease of predominantly right ventricle, characterized by
      ventricular arrhythmias possible leading to sudden cardiac death. Genetic
      predisposition was confirmed more than 15 years ago. Autosomal dominant are forms
      ARVD1-9, Naxos disease (with subtype Carvajal syndrome) is recessive. In ARVC/D
      forms associated with desmosomal disorders are ventricular arrhythmias caused by
      the presence of myocardial damage and in forms associated with ryanodine receptor
      mutation is electrical instability and subsequent myocardial damage caused by
      calcium cell overload. Main clinical signs are ventricular arrhythmias originated
      from areas with slow conduction. Progression of ARVC/D is manifested by RV
      dilatation and LV echocardiographic abnormalities both considered as main risk
      factors of fatal ventricular arrhythmias and sudden cardiac death. Therapeutic
      possibilities include antiarrhythmic drugs, catheter ablation and implantation of
      cardioverter-defibrillator, in severe right or both ventricle involvement even
      heart failure treatment (Tab. 1, Ref. 56).

PMID- 16457042
TI  - Resection of multiple lung metastases--where are the limits?
AB  - Multiple lung metastases present a serious and challenging problem with
      increasing incidence for thoracic surgeons. In the lung metastasis management a
      significant role belongs to laser lung-parenchyma-saving resection. This
      parenchyma saving technique allows a removal of significant higher number of lung
      nodules in comparison to conventional techniques (stapler, clamp resection).
      Performing the lung metastasectomy by this manner, the only remaining question is
      the limitation of this technique. In this retrospective study, the results after
      Nd:YAG Laser (1318 nm, 40 Watt) interventions are being presented, the
      limitations of this technique are being discussed (Tab. 3, Fig. 4, Ref. 9).

PMID- 16457043
TI  - Serum cholinesterase activity and proteosynthetic function of liver in patients
      with diabetes mellitus.
AB  - INTRODUCTION: Diabetes mellitus is associated with a lot of changes in
      intermediary metabolism and several authors reported on higher frequency of liver
      diseases in patients with diabetes. AIM OF THE STUDY: Was to establish the
      changes of blood serum cholinesterase, prealbumin and albumin, parameters which
      are accepted as an index of liver proteosynthetic function, in patients with
      diabetes mellitus. PATIENTS AND METHODS: The study group consisted of 207
      patients with diabetes mellitus (83 patients with type I and 124 patients with
      type II diabetes mellitus). Control group consisted of 179 healthy subjects. The
      activity of cholinesterase was assayed by the kinetic method, concentrations of
      prealbumin and albumin were determined immunochemically. RESULTS: Activity of
      serum cholinesterase was significantly higher in group of patients with diabetes
      mellitus than in control group (65.05 vs 73.33 microkat/l). The concentration of
      prealbumin was lower in blood serum of patients with diabetes than in controls
      (308.10 vs 285.85 mg/l). Serum levels of albumin were not different in both
      studied groups. After dividing of patients according to the type of diabetes, 80
      % of abnormal values of cholinesterase and prealbumin were present in patients
      with type II diabetes. CONCLUSIONS: The results of our study showed abnormal
      values of determined liver tests approximately in 22 % of patients with diabetes
      mellitus. The character of laboratory changes--increased activity of
      cholinesterase, decreased concentration of prealbumin and normal levels of
      albumin, suggests development of liver steatosis in these patients. The most of
      pathological findings were in patients with diabetes type II (Tab. 3, Ref. 20).

PMID- 16457044
TI  - Reported incidence of Lyme disease in Slovakia and antibodies to B. burgdorferi
      antigens detected in healthy population.
AB  - The reported incidence of Lyme disease in Slovakia is indicative of the cyclic
      character of its appearance, which in the last 10 years rated 12.7/100,000 of the
      population with typically summer seasonality, prevalence (+20 %) in women, and
      relative high incidences in the 5-14 and 45-64 age groups. Early forms of the
      disease were manifested in 70 % of all reported cases. Geographically, the spread
      of the disease shows major differences in the number of cases reported in the
      individual districts. Antibodies persist long after the original attack, and
      there is a high incidence of antibodies in the healthy population in endemic
      areas. The presence of antibodies to B. burgdorferi antigens was proven in the
      serum of 250 blood donors by 3 different screening tests in 4.4-15.6 % of all
      persons, signifying different sensitivity as well as specificity levels.
      Subsequent immunoblot examination confirmed the presence of specific antibodies
      in 12.8 % of all persons, implying high exposure of the population in Slovakia to
      this infection, although it obviously proceeds in inapparent forms in the
      majority of cases (Tab. 2, Fig. 4, Ref. 14).

PMID- 16457045
TI  - Radiofrequency coagulation: a new option in early grades of bleeding hemorrhoids.
AB  - BACKGROUND: The treatment for hemorrhoids has undergone significant changes on
      introduction of new techniques in the last few years. Radiofrequency coagulation
      is a new approach for treating grades I and II of hemorrhoids. In this procedure,
      the hemorrhoidal tissue is coagulated by means of high-frequency radio wave. The
      author has described his own experience with this new technique. MATERIALS AND
      METHODS: The procedure was performed using an Ellman radiofrequency generator.
      Over a period of 18 months, patients with bleeding hemorrhoids were treated with
      this technique and a 16-month follow-up was carried out to assess relief in
      bleeding episodes, complications, and recurrence rate. RESULTS: While 13 % of
      patients had persistent or recurrent bleeding, 2 % of patients needed readmission
      for secondary hemorrhage. None had reported with any infective complication. The
      overall ratio of comfort, and patient's satisfaction due to relief of pain and
      bleeding were quite satisfactory. CONCLUSION: The treatment of bleeding
      hemorrhoids by using radiofrequency coagulation is technically simple,
      therapeutically effective and virtually complication-free. The equipment is
      portable, easy to handle, durable, and needs little maintenance. Long-term follow
      up is necessary to justify the reliance on this method (Ref. 49).

PMID- 16457047
TI  - Diagnosis and treatment of brachial plexus injuries.
AB  - In the reconstruction of the nerves in traction injuries of brachial plexus, the
      main role is the correction of the function of upper extremity. This article is
      aimed at establishing a diagnosis, indications for intervention and surgical
      treatment. Operation results are influenced by a degree of injury, type of
      surgical therapy, patient's age, and by the time delay between the injury and the
      intervention (Ref. 6).

PMID- 16457046
TI  - Urgent situations in phlebology--variceal bleeding and it's treatment.
AB  - The aim of this study was to compare the therapeutic results of patients whose
      bleeding points were sutured and patients treated with compression sclerotherapy.
      In the years 1983-2000, 56 patients with profuse bleeding from varicose veins
      were treated. In a subgroup of patients with compression sclerotherapy--Fegan's
      way (32 patients), bleeding wound was healed completely within 7 days on average
      (5-13). All ulcers have healed within 2 months. The presented approach used is a
      surgical procedure (stitch, removal of large varicosities). Fegan's technique of
      compression sclerotherapy, with a detergent sclerosing solution (S.T.D.), enables
      to complete sclerotherapy of all pathological reflux points during 1-2 visits not
      only with good results, but also as a one-day surgery, keeping the patient work
      (Ref. 7).

PMID- 16457048
TI  - The use of titanium miniplates in arthrodesis of the interphalangeal joints and a
      metacarpal neck fracture.
AB  - Fractures of the metacarpals and phalanges are the most common fractures of the
      upper extremity. Hand fractures can be complicated by deformity because of no
      treatment, stiffness due to overtreatment, and both due to inappropriate
      treatment. "Boxer's" fractures of the fifth metacarpal neck are rarely seen in
      professional boxers, they are fare more common in people who hit solid objects
      such as walls. Controversy exists regarding the optimum treatment. General
      indications for arthrodesis of hand joints of the hand include pain, instability,
      or deformity combined with a loss of motor control or bony stock sufficient to
      support arthroplasty. When all previous attempts to restore painless motion fail,
      arthrodesis of the joint becomes the method of choice. The most commonly
      arthrodesed finger joints are distal interphalangeal (DIP), proximal
      interphalangeal (PIP) and the interphalangeal (IP) joint of the thumb. The
      position of joint arthrodesis should be individual depending on the patient's
      needs. (Fig. 13, Ref. 6).

PMID- 16457050
TI  - Paroxysmal disorders and the autonomic nervous system in pediatrics.
AB  - The autonomic nervous system (ANS) plays a complex and vital role in involuntary
      homeostasis of bodily function. This paper discusses the function and dysfunction
      of the ANS in common pediatric paroxysmal disorders including epilepsy, breath
      holding spells, and syncope.

PMID- 16457051
TI  - Use of repetitive nerve stimulation in the evaluation of neuromuscular junction
      disorders.
AB  - Neuromuscular junction (NMJ) disorders are characterized by fuctuating muscle
      weakness. Acquired myasthenia gravis is the most common NMJ disorder with an
      overall prevalence in United States estimated at 60,000. Depending on the site of
      neuromuscular transmission failure, NMJ disorders have been classified as: (1)
      presynaptic (e.g., Lambert-Eaton myasthenic syndrome), (2) synaptic (e.g.,
      cholinesterase inhibitor toxicity), and (3) post-synaptic (e.g., myasthenia
      gravis). Electrodiagnostic techniques used for investigation of NMJ disorders
      include repetitive nerve stimulation (RNS) and single fiber electromyography
      (SFEMG). Recent literature widely explores the use of SFEMG in the diagnosis and
      monitoring of myasthenia gravis, but this technique has a lesser role in the
      daily clinical practice outside of academic institutions. RNS is not as sensitive
      as SFEMG, but it is the most widely used electrodiagnostic method in the
      evaluation of suspected neuromuscular transmission disorders. RNS is technically
      easier and does not require special technical training and skill as SFEMG.
      Repetitive nerve stimulation was utilized first by Jolly in 1895 using an
      electrical drum and faradic tetanization to demonstrate a "myasthenic reaction"
      (weakening muscle contractions). In 1941, decremental response following the
      repetitive nerve stimulation was described by Harvey and Masland. While the
      technology has improved tremendously since then, the RNS testing is still based
      on supramaximal repetitive nerve stimulation and the measurement of decremental
      (or incremental) responses.

PMID- 16457049
TI  - Update on anesthetic and metabolic effects during intraoperative
      neurophysiological monitoring (IONM).
AB  - Various agents are utilized in the operating room to produce anesthetic effects.
      These include barbiturates, halogenated inhalation agents, narcotics, non
      barbiturate induction agents, and benzodiazepines. These agents have variable
      effects upon the EEG and EP (evoked potential) waveforms at different anesthetic
      levels. Metabolic changes such as body temperature and blood pressure can also
      elicit changes in the EEG and EPs.

PMID- 16457052
TI  - Technical tips: polarity and localization.

PMID- 16457053
TI  - [Research protocol for the mortality atlas of the provincial capitals of
      Andalusia and Catalonia (AMCAC Project)].
AB  - The aim of this work is to make known the multicentric project AMCAC, whose
      objective is to describe the geographical distribution of mortality from all
      causes in census groups of the provincial capitals of Andalusia and Catalonia
      during 1992-2002 and 1994-2000 respectively, and to study the relationship
      between the sociodemographic characteristics of the census groups and mortality.
      This is an ecological study in which the analytical unit is the census group. The
      data correspond to 298,731 individuals (152,913 men and 145,818 women) who died
      during the study periods in the towns of Almeria, Barcelona, Cadiz, Cordoba,
      Girona, Granada, Huelva, Jaen, Lleida, Malaga, Seville and Tarragona during the
      study periods. The dependent variable is the number of deaths observed per census
      group. The independent variables are the percentage of unemployment, illiteracy
      and manual workers. Estimation of the moderated relative risk and the study of
      the associations among the sociodemographic characteristics of the census groups
      and the mortality will be done for each town and each sex using the Besag-York
      Mollie model. Dissemination of the results will help to improve and broaden
      knowledge about the population's health, and will provide an important starting
      point to establish the influence of contextual variables on the health of urban
      populations.

PMID- 16457054
TI  - [Is lead used in sports (hunting, shooting and angling) an underestimated public
      health problem?].
AB  - Ammunition and fishing weights used in recreational hunting, shooting and fishing
      sports have been made traditionally with lead. In Spain, for example, hunters and
      shooters are responsible for the dispersion of some 6000 tonnes of the heavy
      metal yearly, into wetland and dryland areas, and an estimated 100 tonnes are
      contributed by anglers to the aquatic zones. The few legal measures that several
      countries have adopted banning the use of the lead in these sports are based on
      the irrefutable proof that every year millions of birds were poisoned lethally,
      due to the inadvertent ingestion of lead shot and sinkers found in their
      habitats. We analyzed whether the present conservationist approach to the problem
      is suitable, and if the evidence of damage to human beings is, or is not,
      sufficient to warrant even more prohibitive measures, especially because, in
      children, there is no safe exposure to lead. We conclude that in some areas
      adequate information already exists, although in others the toxicological
      epidemiological studies are still scanty, suggesting that the topic has been
      given little attention. We are concerned that the Precautionary Principle has not
      been applied to solve this problem whose health effects will be more long-term
      than immediate, especially given the array of lead substitutes available.

PMID- 16457055
TI  - [Integrated health care organizations: guideline for analysis].
AB  - There has been a tendency recently to abandon competition and to introduce
      policies that promote collaboration between health providers as a means of
      improving the efficiency of the system and the continuity of care. A number of
      countries, most notably the United States, have experienced the integration of
      health care providers to cover the continuum of care of a defined population.
      Catalonia has witnessed the steady emergence of increasing numbers of integrated
      health organisations (IHO) but, unlike the United States, studies on health
      providers' integration are scarce. As part of a research project currently
      underway, a guide was developed to study Catalan IHOs, based on a classical
      literature review and the development of a theoretical framework. The guide
      proposes analysing the IHO's performance in relation to their final objectives of
      improving the efficiency and continuity of health care by an analysis of the
      integration type (based on key characteristics); external elements (existence of
      other suppliers, type of services' payment mechanisms); and internal elements
      (model of government, organization and management) that influence integration.
      Evaluation of the IHO's performance focuses on global strategies and results on
      coordination of care and efficiency. Two types of coordination are evaluated:
      information coordination and coordination of care management. Evaluation of the
      efficiency of the IHO refers to technical and allocative efficiency. This guide
      may have to be modified for use in the Catalan context.

PMID- 16457057
TI  - [Impact of systematic vaccination with the antimeningococcal C conjugated vaccine
      in a health area in Andalusia].
AB  - BACKGROUND: A retrospective longitudinal study of population incidence was made
      to assess the effectiveness of meningococcal serogroup C conjugate vaccine, after
      its mass introduction in children in the geographic area of a health district,
      measuring its population impact, and we have studied the state of the
      meningococcal disease. METHODS: Vaccine coverage in children born between 1991
      and 2001, and rates of incidence in declared cases of meningococcal disease in
      seven epidemiological seasons (1997/98 to 2003/04) were calculated. The impact of
      vaccination against serogroup C meningitis was assessed comparing the average
      annual rates of previous and later seasons to the vaccination campaigns in
      population younger and older than 10, using the Fisher exact test. RESULTS: In
      all the study period, 109 cases of meningococcal disease were declared, of which
      50 were of serogroup C meningococcal disease. Starting from 2000/2001 season the
      incidence of serogroup C disease decreased in the population below 10. In this
      age group, the annual average rate of post-vaccine seasons decreases in respect
      to pre-vaccine (from 8.2 to 2.0 per 100,000 inhabitants) showing a statistically
      significant difference. In the population above 10 years, this incidence
      reduction was not observed. In the study period, no case of vaccine failure was
      declared. CONCLUSIONS: The absence of vaccine failure and the impact observed on
      the incidence of serogroup C meningococcal disease in children under 10 suggests
      the effectiveness of this new conjugate vaccine, together with suitable
      vaccination conditions (vaccination schedule, high catch-up, etc.) which are
      developing in our health district.

PMID- 16457056
TI  - [Coverage and association with clinical variables of antipneumococcal vaccination
      of the population over 65 years old in Tarragona-Valls].
AB  - BACKGROUND: In Catalonia, a polyanccharide pneumococcal vaccine (PPV) programme
      which includes subjects over 65 years old, was started in 1999. Three years
      later, we study the vaccine cover in relation to the presence of risk factors for
      pneumonia. METHODS: Cross-sectional observational study conducted in 8 Basic
      Health Areas (BHA) of Tarragona. All the subjects over 65 years old and assigned
      to one of the 8 basic health areas participating in the study were included
      (n=11241). Using computerized clinical records and vaccination records we
      evaluated whether each patient had received PPV before January 2002, and the
      presence of disease or risk factors for pneumonia. RESULTS: Global vaccination
      coverage was 44.4% (37.1% in 65-74 years, 53.9% in 75-84 and 51.5% in 85-99
      years). The greatest coverage was recorded in subjects with active neoplasm
      (56.7%), chronic necropathy (55.3%). chronic lung disease (54.2%) and chronic
      cardiopathy (53.5%). The least coverage was recorded in smokers (38.9%),
      alcoholic patients (43.6%) and chronic liver disease (46.5%). AVP coverage was
      38.9% (CI 95%: 37.6-40.2) in subjects without any risk factors, 47.7% (CI 95%:
      46.1-49.4) in those with one factor, and 52.7% (CI 95%: 52.6-54.8) in those with
      two or more factors. CONCLUSIONS: In spite of an acceptable global coverage,
      there are large subgroups of high risk patients who have not received PPV. The
      results suggest that, in an attempt to achieve extended global coverage, the
      presence of risk factors is largely ignored when deciding whether to prescribe
      PPV or not.

PMID- 16457058
TI  - [Use of acetylcholinesterase inhibitors and memantine in Alzheimer-type
      dementia].
AB  - BACKGROUND: The therapeutic options to treat Alzheimer-type dementia (ATD) in
      recent years, have made it increasingly necessary to become familiar with the
      employment pattern of these new medicinal products. METHODS: A cross-sectional
      observational study of the population with ATD treated with acetylcholinesterase
      inhibitors and/or memantine in the Gallician Health Service. Databases were
      compiled with the demographic variables and use data during April 2005 of the
      medicinal products studied. RESULTS: Of the 5110 patients with ATD, 70.47% were
      women. The mean age of the women was 80.12 and of the men was 78.61 years old,
      with standard deviations of 6.66 and 7.03, respectively. The female sex was one
      of the factors associated with presenting ATD to pharmacological treatment (OR:
      1.932 [CI 95%: 1.819-2.052]). The medication used most was donepezyl (44.46% of
      patients). Significant differences were found in that memantine was used to treat
      more patients in the group of patients < or =64 years (19.7% in < or =64 years
      vs. 14% in >64 years [p < 0.05]), and donepezyl was preferentially used in
      patients > or =95 years (75% in > or =95 years vs. 46.9% in <95 years [p <
      0.03]). No significant differences were observed in the use of anti-dementia
      therapy, expressed in DDD/patient/day between the sexes, age groups, or in the
      age groups separated according to sex. CONCLUSIONS: The use of memantine (in
      monotherapy or in combination) is more frequent in patients under 64 years old.
      Female sex was found to be a factor associated with presenting ATD to
      pharmacological treatment.

PMID- 16457059
TI  - [Trends in mortality in a Spanish prison from 1994-2004].
AB  - BACKGROUND: [corrected] Few works have focused on studying mortaty in prisons.
      The objective here is to study the causes and incidences of mortality in a
      Spanish prison. METHODS: Descriptive study of the deaths in a prison between 01
      01-1994 and 31-12-2004. The following variables were recorded: sex, date of
      death, HIV serology, number of CD4+ where relevant, and cause of death according
      to the following classification: death by HIV, by non-HIV disease, suicide, drug
      overdose and accidents. After indirect standardisation of incidence, we compared
      mortality in the Centre with the other Spanish prisons. We established mortaality
      rate tendencies by a linear regression model. RESULTS: 42 deaths, 41 men, 1
      woman. Median age 33.10 years (27.72-36.12; IQR: 8.40). 30 (71.4%) HIV+, with a
      median of 177 CD4+ lymphocytes/microl. Twenty patients (45.24%) died from HIV, 15
      (38.10%) from non-HIV diseases, 3 (7.14%) from suicide, 3 (7.14%) from drug
      overdose and 1 (2.38%) accidentally. Crude mortality rates corresponded to
      12.605% per hundred of inmates/year in 1997 and 1.758%, inmates/year in 2003,
      with a decreasing trend of 0.976 deaths % per hundred, inmates/year (CI 95%:
      0.399-1.552; p = 0.004). After standardising rates, we obtain 28.6 expected
      deaths daring the period, with an SMR of 1.4679. CONCLUSIONS: Although it follows
      a decreasing trend, the mortality rate obtained during the study period was
      higher than expected. The main cause of mortality was acquired immunodeficiency
      syndrome.

PMID- 16457060
TI  - [Clinical and psychosocial characteristics of subjects with fibromyalgia. Impact
      of the diagnosis on patients' activities].
AB  - BACKGROUND: Little is known today about the characteristics of individuals
      diagnosed with fibromyalgia, their degree of disability and the health system
      response system response to this condition. The objectives of this work include:
      to establish the sociodemographic, clinical and psychosocial profile of male and
      female patients with fibromyalgia. To describe the response they receive from the
      health service, and to study the repercussions of this syndrome on the daily
      activities of subjects who suffer it, including its effects on their work
      environment. METHODS: Descriptive cross-sectional study. The information was
      received from telephone interviews of individuals diagnosed with fibromyalgia in
      the Hospital Universitario Virgen de las Nieves in Granada during 2003. RESULTS:
      92.1% of those interviewed were women. Fibromyalgia caused work absenteeism in
      31.4% of cases; and 64% regarded their health as poor or very poor. Fibromyalgia
      was associated with other diseases in 52.3% of cases. The family doctor is the
      specialist consulted before diagnosis in 92.1% of cases. A total of 50.5% had a
      history of psychiatric disorders, these were still present at the time of
      interview in 36.4%. Around 71% of the sample received family support, and 70.1%
      of cases considered the disease to seriously affect their environment.
      CONCLUSIONS: Fibromyalgia was mainly diagnosed in women. Subjects with this
      syndrome have a poor perception of their own health and work situation, and it
      negatively affects their family environment.

PMID- 16457061
TI  - [Social participation in health: user community leaders, managers and policy
      makers in Colombia. A qualitative view].
AB  - BACKGROUND: Health sector reforms taking place in Colombia during the Nineties
      included policies to promote social participation in the health system, which is
      considered essential to its functioning. The aim of this article is to analyse
      the meaning and the significance of participation in health for the different
      social actors involved in implementing policies in Colombia. METHODS: A
      qualitative, descriptive, exploratory study was carried out using focal groups
      (FG) and semi-structured individual interviews (I) of the different social
      actors: 210 users (FG), 40 community leaders (FG), 3 policy makers (E) and 36
      healthcare professionals (E). A carried out analysis was content up of the
      contents. The study area corresponded to the municipalities of Tulua and Palmira
      in Colombia. RESULTS: The concept of participation was interpreted differently
      depending on the actor studied: for users and leaders the concept referred to
      contributing ideas, presence in social spaces, solidarity and frequently, and use
      of the health services. Healthcare professionals considered the activities
      carried out by institutions together with the community as social participation,
      the use of services and affiliation to the health system. Policy markers
      considered participation to concern evaluation and control of the health services
      by the community, to improve its quality. CONCLUSIONS: The different concepts of
      participation reveal dif ferences between the content of the policy and how it is
      understood and interpreted by the different social actors in their interaction
      with the health services. These different perspectives must be taken into account
      to develop a link between society and the health services.

PMID- 16457062
TI  - Winning reports by healthcare systems are diverse in focus.
AB  - Three healthcare systems are recognized for their unique annual reports: Kaleida
      Health of Buffalo, NY; Loyola University Health System of Maywood, IL; and
      Meridian Health of Neptune, NJ. Each report reflects the ongoing efforts and
      commitment required to bind a healthcare system into a single, recognizable unit.

PMID- 16457064
TI  - Palo Alto Medical Foundation explores ties that bind.
AB  - Palo Alto (CA) Medical Foundation addresses the mission of its annual report in a
      way that meets the high expectations of its loyal donors.

PMID- 16457063
TI  - Why we'd like to give everyone a prize--and why we don't.

PMID- 16457065
TI  - Community hospital reports focus on people.
AB  - Summit Health of Chambersburg, PA; Rush-Copley Medical Center of Aurora, IL; and
      Little Company of Mary in Evergreen Park, IL, tailor their individual reports to
      the needs and interests of their communities. The results are varied in format,
      style, and tone.

PMID- 16457066
TI  - Regional hospitals reach out to unique populations. Twelve reports named winners
      of annual competition.
AB  - Kudos to Grinnell (IA) Regional Medical Center, St. Anthony Regional Hospital and
      Nursing Home of Carroll, IA, and Columbus (IN) Regional Hospital-true to their
      mandate, each of these award-winners has produced an annual report that reaches
      readers where they live.

PMID- 16457067
TI  - M.D. Anderson Cancer Center continues award-winning style.
AB  - The University of Texas M.D. Anderson Cancer Center in Houston is an institution
      singularly committed to the highest standards of performance and achievement.
      Accordingly, its communications/public relations staff are expected to produce an
      outstanding annual report every year.

PMID- 16457068
TI  - Columbus Children's Hospital invests in its supporters.
AB  - Columbus (OH) Children's Hospital puts its best face forward with this year's
      annual report of philanthropy. This thoughtful collaboration by hospital and
      agency invites each reader to identify with the anxious parents of some patients.
      The compelling copy and illustrations bode well for the report's mission.

PMID- 16457069
TI  - [Why the decrease of cholesterol has stopped, although use of statins is
      increasing?].

PMID- 16457070
TI  - [Young people with bad physical fitness must be educated].

PMID- 16457071
TI  - [Safety of antiinflammatory drugs].

PMID- 16457072
TI  - [Raynaud disease].

PMID- 16457073
TI  - [Early diagnosis of obstructive pulmonary disease from functional tests to
      inflammation detection].

PMID- 16457074
TI  - [Changing epidemiology of gastric and esophageal cancers].

PMID- 16457075
TI  - [Hepatitis E infections as a world wide problem].

PMID- 16457076
TI  - [Acute care of intracerebral hemorrhage is improving].

PMID- 16457077
TI  - [Leg pain and increased D-dimer concentration].

PMID- 16457078
TI  - [Another view to the care after traumatic crisis].

PMID- 16457079
TI  - [Is psychological debriefing beyond evaluation?].

PMID- 16457080
TI  - [Atrial fibrillation].

PMID- 16457081
TI  - Cardiac gas embolism after central venous catheter removal.
AB  - Clinical images reporting intracardiac gas level are sparce and, to our
      knowledge, the presence of gas embolism into the coronary arteries has never been
      reported. We describe the case of a young man who experiences life-threatening
      gas embolism with the presence of gas bubbles into cardiac cavities and coronary
      arteries.

PMID- 16457082
TI  - Oxidative metabolism in platelets, platelet aggregation, and hematology in
      patients undergoing multiple hyperbaric oxygen exposures.
AB  - Repeated hyperbaric oxygen (HBO2) treatments at 2.2 ATA for 90 minutes each are
      used to treat chronically ill patients with problem wounds, but there are
      concerns about the cytotoxicity of oxygen to blood cells and platelet function
      during prolonged HBO2 therapy. We recruited 31 consenting patients scheduled for
      multiple HBO2 treatments to evaluate oxidative metabolism in platelets, platelet
      aggregation, and hematology (mean age +/- standard error, 61 +/- 2.6 years, 20
      males, 11 females). Venous blood was collected before and after the 1st and 20th
      HBO2 treatments. No effect of HBO2 was observed on red cell counts, hematocrit,
      hemoglobin, mean red cell volume (MCV), platelet counts, basal levels of lactate
      production by platelets, ferric reducing ability of plasma (FRAP), or plasma
      protein. The capacity for oxidative metabolism (lactate ratio) in platelets was
      not affected by HBO2, except in smokers where it increased by the 20th HBO2
      treatment. Mean lymphocyte count was increased by 38% after the 20th treatment.
      There was also a 23% increase in platelet protein content, and a 24% increase in
      arachidonic acid-dependent platelet activation. Collagen-dependent platelet
      aggregation was unaffected. Blood glucose showed HBO2-dependent variability, but
      remained in the normal range. Plasma lactate levels decreased significantly from
      3.2 to 2.5 mmol/l by the end of the study. Overall, we found no evidence that 20
      HBO2 sessions caused adverse effects on platelet aggregation or oxidative
      metabolism in platelets, red or white cell counts, or total antioxidant status of
      the plasma.

PMID- 16457083
TI  - Improvement in motor and cognitive impairment after hyperbaric oxygen therapy in
      a selected group of patients with cerebrovascular disease: a prospective single
      blind controlled trial.
AB  - BACKGROUND: Clinical and experimental evidence suggests that a localized decrease
      in oxygen brain tissue availability contributes to the neurological deficit in
      patients with cerebrovascular disease (CVD) who also present with frontal
      leukoaraiosis (LA) (periventricular hypodensity on CT scan) and lacunar infarcts.
      In a prospective controlled trial blinded to patients but not to investigators,
      we tested the effect of HBO2 on this group of patients. METHODS: Selected
      patients with symptomatic CVD, LA and lacunar infarcts received daily exposures
      of 45 minutes for 10 days to hyperbaric oxygen (n=18, HBO2 group) or hyperbaric
      air (n=8, control group). The control group subsequently received HBO2. Scores of
      conventional scales for motor and cognitive functions were obtained and
      videotaped before and after exposure. After the exposures, participants were
      followed on a monthly basis with systematic clinical neurological examination for
      up to 6 months. Results. There was a statistically significant improvement in all
      scales for the HBO2 group compared with the placebo group and in the placebo
      group after receiving HBO2 (p<0.05). Neurological improvement persisted in the
      majority of patients for up to 6 months. Repetition of the HBO2 protocol in 9
      patients in whom symptoms recurred after 6 months resulted in improvement of
      symptoms. CONCLUSIONS: These data provide evidence consistent with the notion
      that HBO2 improves neurological function in patients with CVD, lacunar infarcts
      and frontal LA. Because of the lack of investigator blinding and a relatively
      small sample size in this study, larger, randomized controlled studies are needed
      to further test this hypothesis and to further define the role of oxygen therapy
      for brain repair in chronic brain disease.

PMID- 16457084
TI  - Pulmonary effects of submerged oxygen breathing: 4-, 6-, and 8-hour dives at 140
      kPa.
AB  - Elevated inspired oxygen partial pressures (PO2) may cause pulmonary oxygen
      toxicity (PO2T). However, normal variability and water immersion also cause
      pulmonary function (PF) changes. In 21 subjects, we measured the variability of
      flow-volume parameters and diffusing capacity for carbon monoxide (DLCO) for six
      weeks without diving. In 24 divers, we compared the effects of air (P(I)O2 = 0.3
      atm = 30 kPa) and oxygen (P(I)O2 = 1.4 atm = 140 kPa) during paired resting dives
      of 4, 6, or 8 hours in a freshwater pool 4.6 m deep. Without diving, median
      coefficients of variation (CV) were: vital capacity, 3.2%; FEV1, 3.5%; peak flow,
      7.0%; and DLCO, 5.9%. Measurements within 2.4.CV of baseline were considered
      unchanged. After 4-, 6-, and 8- hour air dives, PF decreased in one, one, and
      four subjects, respectively, and three, one, and two, respectively, reported
      symptoms. After the oxygen dives, PF decreased in two, three, and four subjects,
      respectively, and two, four, and seven, respectively, reported symptoms. PO2T
      persisted for several days after 8-hour oxygen dives.

PMID- 16457086
TI  - Probability of decompression sickness in no-stop air diving and subsaturation
      diving.
AB  - Probabilistic models allow estimation of the probability (Pdcs) that
      decompression sickness (DCS) will occur in any particular dive. Our objective is
      to provide Pdcs estimates for no-stop diving instructions used by the U.S. Navy
      and various other navies. To do so, we develop statistics-based (probabilistic)
      and intuition-based (deterministic) models using dive-outcome data from the U.S.
      Navy Decompression Database. We give special attention to subsaturation dives
      (defined as no-stop dives shallower than 40 fswg with bottom times between 4 hr
      and one day), for which experimental dives are scarce. According to our models,
      probability of DCS is 2% or less for current U.S. Navy no-stop air dive schedules
      and near 1% for the navies of Great Britain, Canada, and France; also the current
      U.S. Navy prescriptions for subsaturation dives seem to be appropriate. Our
      probabilistic models fail for deep dives; they do not avoid observed DCS cases in
      the calibration dataset and provide longer no-stop times than allowed by tables
      used operationally; we advocate prescriptions by our deterministic model for deep
      no-stop dives.

PMID- 16457085
TI  - Hawaiian deep treatments: efficacy and outcomes, 1983-2003.
AB  - This paper reports on the outcomes and efficacy of the deep treatment schedules
      employed at the University of Hawaii to treat diving accident victims. These
      tables utilize increased atmospheric pressures, several mixed gas combinations,
      and a more gradual staged decompression rate than US Navy treatment schedules.
      The majority of our study population (72.4%) was treated using a single specific
      treatment schedule. 90% were treated using deep tables either singly or in
      combination with other tables. 91.6% of cases treated on deep tables achieved
      complete functional recovery. The percentage of cases obtaining complete
      functional recovery ranged from 91.3% to 99% based upon condition treated, and
      from 77.5% to 100% based upon treatment schedule employed. Number of treatments
      required by type of injury ranged from 1.3 to 2.4 treatments. 74.5 % of cases
      required two or less treatments to obtain complete functional recovery. Severity
      of injury and age of the diver were the most sensitive predictors of outcome
      while delay to treatment did not influence outcomes in this study population.

PMID- 16457087
TI  - Effect of 2.1 MPa and 4.1 MPa H2O2 exposure on auditory brain stem evoked
      potential in mice.
AB  - Brain auditory evoked potential (BAEP) in mice exposed to hyperbaric H2O2
      pressure was monitored to reveal the correlation between altered synaptic
      transmission and hydrogen narcosis or isobaric HPNS. Inter peak latencies and
      wave amplitudes were selected as indices of assessment. The animals were exposed
      either to He-O2 or H2-O2 at 2.1 MPa and 4.1 MPa. Results showed that synaptic
      transmission was inhibited to various extents. The inhibition was partly due to
      the narcotic effect of hydrogen, which was added to the effect caused by
      hydrostatic pressure. On the other hand, asymmetrical reaction of each segment in
      the neuro-network might be responsible for the occurrence of HPNS.

PMID- 16457088
TI  - Psychometric characteristics of the child occupational self-assessment (COSA),
      part two: refining the psychometric properties.
AB  - Self-assessment is an appropriate way to support client-centered practice and
      promote personal development in young occupational therapy clients. This study,
      the second study in a series of two, sought to refine the psychometric properties
      based on previous analysis of the Child Occupational Self-Assessment (COSA), a
      self-report tool based on the Model of Human Occupation. The COSA comprises 24
      statements, which the child rates in terms of personal competence and importance.
      The Rasch Rating Scale Model was used to evaluate the measurement properties of
      the Competence and Values scales that result from these self-ratings. The
      original three-point rating scale was expanded to four response categories in
      this study, which resulted in improved reliability and sensitivity. In this
      second study, the items once again coalesced to form measures of competence and
      values, and the order of items from less to more competence and value was similar
      to that in the first study, supporting the internal validity of the COSA scales.
      The results provide evidence that the COSA can be used as meaningful and reliable
      client-directed assessment tool as well as an outcome measure.

PMID- 16457090
TI  - Reliability and validity of the Swedish version of the Fatigue Impact Scale
      (FIS).
AB  - Fatigue is a complex phenomenon that, for those not affected, is hard to
      understand. To achieve better assessments, caregivers need reliable and valid
      tools. The aim of this study was to investigate the reliability and validity of
      the Swedish version of the Fatigue Impact Scale (FIS) among working-aged
      individuals diagnosed with multiple sclerosis (MS), as well as in a comparative
      group randomly selected from the general population in the same geographical
      area. Both individuals with MS (n=161) and individuals recruited from the general
      population (n=194) participated in the study. A questionnaire was used for the
      data collection. The data were analysed using non-parametric statistical methods.
      Reliability of FIS was addressed by item-to-item and item-to-total correlations.
      Concurrent validity was tested for by analysing correlations between the FIS and
      general questions, and construct validity by investigation of differences in the
      FIS scores between known groups. The FIS was found to be homogenous, with item-to
      total correlation coefficients of 0.42 < or = s < or = .86 (p <0.001), reflecting
      the instrument's reliability. The correlations between the FIS and the general
      questions confirm its concurrent validity, 0.27 < or = s < or = .84 (p <0.001).
      The differences in FIS scores between known groups demonstrate its construct
      validity. Furthermore, the FIS showed the ability to discriminate between groups
      of individuals with differences in perceived impact of fatigue.

PMID- 16457089
TI  - Lifeworld perspectives on assistive devices: lived experiences of spouses of
      persons with stroke.
AB  - The purpose of this study was to explore how spouses of persons with a disability
      following stroke describe their lived experiences regarding assistive devices in
      everyday life. A phenomenological lifeworld approach was used and conversational
      interviews were conducted with 12 spouses. Their lived experiences of assistive
      devices were explored in relation to four lifeworld existentials intertwined in
      everyday life. The results showed that lived body concerns aspects of feelings,
      habits, and incorporation of the devices with one's own body. The devices are,
      from the spouses' perspective, a prerequisite for their partner with stroke
      living at home. Successively the devices are incorporated into the couples'
      homes, and they provide a new view of the environment, aspects related to lived
      space. The devices bring about a changed relation to lived time, related to past,
      present, and future. Further, lived human relation concerns changed relationships
      to husbands/wives with stroke, including a great responsibility due to the
      devices and their usage. The results also included stigmatizing aspects and a
      twofold relationship to health professionals regarding participation in decisions
      about prescribing assistive devices. Understanding the unique meaning of
      assistive devices from the spouses' perspective is vital for occupational
      therapists prescribing such devices.

PMID- 16457091
TI  - Assistive devices among very old people in five European countries.
AB  - The aim of this study was to investigate the use and need of assistive devices
      (ADs) in a cross-national European sample of very old persons, focusing on
      national similarities and differences as well as similarities and differences
      according to age and level of health status. Data from the ENABLE-AGE research
      project were utilized involving very old persons in Sweden, Germany, Latvia,
      Hungary, and the United Kingdom (UK). Personal interviews with single-living old
      persons were conducted (n = 1918). Of the total sample 65% reported that they had
      and used one or more ADs, and 24% reported unfilled need. The most commonly used
      ADs were devices for communication, followed by devices for mobility.
      Participants in Hungary and Latvia used a lower total number of ADs. Comparisons
      among sub-groups according to age between the Western and the Eastern European
      national samples showed significant differences. The result can to some extent be
      explained by different welfare systems and presumably differences in knowledge
      and awareness of ADs, and further research is called for. However, the result can
      serve as input for future planning and development of information, services, and
      community-based occupational therapy, to improve healthcare and social services
      for older people.

PMID- 16457092
TI  - National Rural Health Mission--a good beginning.

PMID- 16457093
TI  - Women friendly health services--a definite step to reduce maternal morbidity and
      mortality.

PMID- 16457094
TI  - Universal access to health--a rights based approach.

PMID- 16457095
TI  - Leprosy in India--present scenario and the task ahead.

PMID- 16457096
TI  - Public health infrastructure in rural India: challenges and opportunities.

PMID- 16457097
TI  - Increasing access to cataract surgery in a rural area--a support strategy.
AB  - The objectives of the study were to elicit the reasons for not undergoing
      cataract surgery from those having cataract, aged 50 years and above, in a
      village community and, develop, implement and assess a support strategy for
      getting cataract surgery done. The leading reasons identified were monetary
      constraints (18.8%), transport difficulty (17.4%), lack of awareness about
      cataract in the eyes (17.4%) and lack of escort (14.5%). Based on the identified
      reasons, patients were transported in groups to a government eye hospital for
      free surgery after completion of required pre operative formalities at the
      village health center itself. Out of 65 eligible individuals, 66.2% underwent
      surgery. The success of the approach was evident by perceived improvement in
      vision in 88.4% operated patients, occurrence of only few minor complications and
      a satisfactory hospital experience being reported by all.

PMID- 16457098
TI  - Iodine deficiency disorders among school children of Dakshin Dinajpur District,
      West Bengal.
AB  - Iodine deficiency disorders (IDD) are major public health problems in India,
      including West Bengal. Existing programme to control IDD needs to be continuously
      monitored through recommended methods and indicators. Thus we undertook the study
      to assess the prevalence of goiter, status of urinary iodine excretion (UIE)
      level and to estimate iodine content of salts at the household level in Dakshin
      Dinajpur district, West Bengal. We conducted a community-based, cross-sectional
      study in 2004; among 2250 school children, aged 8-10 years. The '30 cluster'
      sampling methodology and indicators for assessment of IDD, as recommended by the
      joint WHO/UNICEF/ICCIDD consultation, were used for the study. Goitre was
      assessed by standard palpation technique, UIE was analyzed by wet digestion
      method and salt samples were tested by spot iodine testing kit. Of the 2250
      children, 419 (18.6%) had goitre (95% CI = 17.0 - 20.2%). Total goitre rate (TGR)
      was not significantly different in respect of gender, age and religion. Visible
      goitre rate was 2.5%. Median urinary iodine excretion level was 16 mcg/dL
      (normal: > or = 10 mcg/dl.) and 16.5% children had value less than 5 mcg/dL. Only
      67.4% of the salt samples tested had adequate iodine content of > or = 15 ppm,
      with significant difference between Hindus and Muslims (chi2 = 12.68, d.f. = 1, p
      < 0.01). TGR of 18.6% indicate the district is still endemic for IDD, but median
      urinary iodine within normal range reflects no current iodine deficiency. The
      district is in the transition phase from iodine-deficient to iodine-sufficient.
      Measures are to be sustained for successful transition towards elimination.

PMID- 16457099
TI  - Impact of educational status on AIDS awareness and attitude: a micro study of
      Krishnanagar City.
AB  - The study was carried out at Krishnanagar city of Nadia District, West Bengal on
      aims to focus the HIV/AIDS related awareness and attitudes. A total of 400
      samples divided into illiterate, primary, secondary and higher educated people
      (100 from each group) were surveyed using "5-point Likert Scale" consisting of
      two parts-Part-I for measuring attitude and Part-II for measuring awareness. The
      data were collected at the end of 1999 and analyzed using SPSS computer
      programme. Results revealed subjects of any categories of people in general were
      not aware and shows negative attitude towards AIDS. Significant differences were
      existed among the categories except between illiterate & primary and secondary &
      higher educated group of people about awareness and attitude towards AIDS.

PMID- 16457100
TI  - Comparative study of knowledge about different Child Survival and Safe Motherhood
      intervention in two groups of mothers.
AB  - A cross-sectional study was conducted in an urban field practice slum area served
      by Urban Health Centre (UHC) attached to the Dept. of Preventive and Social
      Medicine, T. N. Medical College and Nair Hospital, Mumbai, to compare the
      knowledge about different Child Survival and Safe Motherhood interventions in two
      groups of mothers. 152 mother who regularly attended antenatal check-up in UHC
      constituted study group and 153 mothers selected by individual matching
      constituted the control group. Significant differences in the knowledge of study
      and control groups of mothers were observed about some interventions like time of
      initiation of breast feeding, duration of exclusive breast feeding, age of
      starting weaning and number of OPV and DPT doses to be given till 1 year of age.

PMID- 16457101
TI  - Morbidity pattern and time trends of filaria cases at a PHC in Dakshina Kannada
      District.
AB  - A study on morbity pattern and time trends of filaria cases was carried out in a
      PHC of Dakshin Kannada District during November 2000 to January 2001. The age and
      sex distribution of all 416 filaria cases recorded revealed that 235 (56.49%)
      were females and maximum concentration of 263 (63.21%) was in the age group of 16
      45 years. The seasonal distribution revealed that rainy season accounted the
      highest number of cases 197 (47.35%). The prevalence was highest, 1.96/1000
      population in the year 1993 and lowest, 0.71/1000 population in the year 1995.

PMID- 16457102
TI  - Reproductive tract infection: an experience in rural West Bengal.
AB  - A community based cross-sectional study was conducted in the villages of Singur
      block, Hooghly district, West Bengal during September 2000 to February 2001. The
      objectives of the study were to find out the magnitude of Reproductive Tract
      Infections (RTI) among reproductive age group women, their knowledge about RTI
      and utilization of service available locally. Out of an estimated 896 women of
      reproductive age group in the study area, 186 women were selected by multistage
      random sampling technique. The study revealed that 66.1% respondents experienced
      one or more symptoms of RTI in four weeks recall period of this study. There was
      significant association (p < 0.01) between literacy status and their experiences
      of reproductive illness. 57% had knowledge about RTI. This increased gradually
      with increase of their ages (p < 0.01); literacy status (p < 0.01) and their
      socio-economic condition (p < 0.05). 27.6% of RTI patient did not receive any
      treatment, and majority of those received treatment (41.5%) sought advice from
      private practitioners.

PMID- 16457103
TI  - [Abortion rate among students are increasing].

PMID- 16457104
TI  - [How should be dermatological care be developed?].

PMID- 16457105
TI  - [Anders Jahre award given to Sirpa Jalkanen].

PMID- 16457106
TI  - [Year 2005 Anders Jahre Young Scientist Award goes to Olli Ritvos].

PMID- 16457107
TI  - [Foreign object in the nose].

PMID- 16457108
TI  - [Pain generated from intervertebral discs].

PMID- 16457109
TI  - [Irregular gynecological bleeding among young fertile women].

PMID- 16457110
TI  - [Blue eyes on dark background. Waardenburg syndrome].

PMID- 16457111
TI  - [Update on current care guidelines. Depressive disorder].

PMID- 16457112
TI  - [About the appreciation of clinical teaching].

PMID- 16457113
TI  - [Control to the number of PhD thesis among medical doctors].

PMID- 16457114
TI  - [Diabetic with hallucination].

PMID- 16457115
TI  - [AA- sculpture by Kari Caven].

PMID- 16457116
TI  - [New trend in oral health care].

PMID- 16457117
TI  - [From the general health care law to guaranteed care-annual dental checkup].

PMID- 16457118
TI  - [Oral complications in patients with rheumatoid arthritis].

PMID- 16457119
TI  - [Alcohol, cigarettes and microbes in the etiology of oral cancer].

PMID- 16457121
TI  - [Oral health care of patients with renal disease].

PMID- 16457120
TI  - [Osteomyelitis of mandible-rare cause of facial pain].

PMID- 16457122
TI  - [Modern slice imaging in dental medicine].

PMID- 16457124
TI  - 13C-octanoic acid breath test in functional and organic disease: critical review
      of literature.
AB  - The 13C-octanoic acid breath test is considered a useful tool to measure gastric
      emptying both in physiological and pathological conditions. Many studies have
      concerned functional dyspepsia. Recently, breath test has been used in predicting
      a delayed gastric emptying in subsets of dyspeptic symptoms. In detail only
      postprandial fullness and vomiting are resulted significantly correlated with
      delayed solid emptying. Besides in the patients with dyspepsia and irritable
      bowel syndrome associated, intestinal disturbances did not seem to contribute to
      delay gastric emptying. In diabetic patients octanoate test has confirmed the
      percentages of delayed emptying obtained by means of scintigraphy. In other
      organic states (celiac disease, cirrhosis, renal failure, neurological disease,
      etc) most of reports have proved a delayed emptying of solids. In GERD and ulcer
      disease gastric function is resulted normal, being accelerated in distal
      gastrectomy and in hyperemesis gravidarum. From pathophysiological point of view
      Helicobacter pylori, extrinsic autonomic neuropathy (apart from diabetes) and
      autoimmunity do not seem to relate with gastric emptying, both in functional and
      organic disease.

PMID- 16457123
TI  - 13C-octanoic acid breath test for measuring gastric emptying of solids.
AB  - Non invasive evaluation of gastric emptying is generally performed by
      scintigraphy which is, however, difficult to perform and not suitable to children
      and childbearing women. A new method based on stable isotope breath testing
      analysis has been introduced in clinical practice: the 13C-octanoic acid breath
      test. In this paper, an overview of the current knowledge on this technique is
      given with special emphasis on the principle of the test, the mathematics used to
      analyse the results, and the physiological, pathological, and pharmacological
      aspects of gastric emptying studied with this new method.

PMID- 16457125
TI  - Gastric emptying and intragastric balloon in obese patients.
AB  - BACKGROUND: Intragastric balloons have been proposed to induce weight loss in
      obese subjects. The consequences of the balloon on gastric physiology remain
      poorly studied. We studied the influence of an intragastric balloon on gastric
      emptying in obese patients. PATIENTS AND METHODS: 12 patients were included in
      the study, with BMI (mean +/- SD) of 38.51 +/- 4.32 kg/m2. The balloon was
      inserted under light anaesthesia and endoscopic control, inflated with 700 ml
      saline, and removed 6 months later. Body weight and gastric emptying (T1/2 and T
      lag) using 13C-octanoic acid breath test were monitored before balloon placement,
      during its permanence and 2 months after removal. RESULTS: Mean weight loss was:
      6.2 +/- 2.3 kg after one month; 12.4 +/- 5.8 kg after 3 months; 14.4 +/- 6.6 kg
      after 6 months and 10.1 +/- 4.3 kg two months after BIB removal. Gastric emptying
      rates were significantly decreased in the first periods with balloon in place,
      and returned to pre-implantation values after balloon removal. T1/2 was: 87 +/-
      32 min before BIB positioning, 181 +/- 91 min after 1 month, 145 +/- 99 min after
      3 months, 104 +/- 50 min after 6 months and 90 +/- 43 min 2 months after removal.
      T lag was 36 +/- 18 min before BIB positioning, 102 +/- 82 min after 1 month, 77
      +/- 53 min after 3 months, 59 +/- 28 min after 6 months and 40 +/- 21 min. 2
      months after removal. CONCLUSIONS: BIB in obese patients seems to be a good help
      in following the hypo caloric diet, especially during the first three months when
      the gastric emptying is slower and the sense of repletion is higher. After this
      period gastric emptying starts to return to normal and the stomach adapts to BIB
      loosing efficacy in weight loss.

PMID- 16457126
TI  - The role of gastric accommodation in the pathophysiology of functional dyspepsia.
AB  - BACKGROUND AND OBJECTIVES: The pathophysiology of functional dyspepsia is not yet
      completely known. Several mechanisms have been suggested as having a role in
      symptom onset and impaired gastric accommodation to meal is one of the most
      frequent. This review will focus on the pathophysiological and clinical aspects
      of this abnormality. EVIDENCE AND INFORMATION SOURCES: Medical peer-reviewed
      literature was considered to elucidate the role of gastric accommodation in the
      pathophysiology of functional dyspepsia. STATE OF THE ART: Impaired gastric
      accommodation to meal is present in around 40% of patients with functional
      dyspepsia and it was shown to be associated with the presence of early satiety.
      Unfortunately, a definitive treatment of this abnormality with fundus-relaxing
      drugs is not yet available. PERSPECTIVES: Further studies are needed to better
      clarify the role of each single pathophysiological mechanism on clinical
      manifestations of functional dyspepsia. Research is still ongoing to offer a
      valid therapeutic approach.

PMID- 16457127
TI  - Electrogastrography.
AB  - Electrogastrography (EGG) is the recording and the interpretation of gastric
      electrical activity. Recordings can be made from the gastrointestinal mucosa,
      serosa, or skin surface. Because of its ease of use, cutaneous EGG has gained
      wide acceptance. Many technical problems have been solved to obtain a good graph.
      The EGG is usually evaluated in terms of changes in the EGG waves amplitude and
      frequency. Deviations from the normal frequency of 3 cycles per minute may be
      referred to as brachy- or tachyarrhythmia. The clinical use of EGG has been most
      widely evaluated in patients with gastroparesis and functional dyspepsia.
      Scintigraphic gastric emptying is considered the gold standard test for
      evaluating gastroparesis and 13C-octanoate breath test an ideal alternative
      because does not use ionizing radiation. While gastric emptying evaluates the
      efficiency of gastric emptying, EGG focuses on the underlying myoelectrical
      activity. Using both EGG and 13C-octanoate breath test will be possible to detect
      many subset of dyspeptic patients and to understand the underlying problem.

PMID- 16457128
TI  - [Lower motor neuron diseases with predominantly upper limbs affection: are they
      independent forms or atypical variants of amyotrophic lateral sclerosis?].
AB  - We carried out an analysis of 5 sporadic cases of lower motor neuron disease with
      predominant affection of the proximal parts of arms in 2 patients and distal
      parts in 3 patients. From clinical point of view, our own observations, along
      with similar cases reported in the literature with predominantly affected upper
      limbs, different progression of the disease and denervation changes during needle
      EMG, can argue for clinical heterogeneity of lower motor neuron disease. There
      were some difficulties in establishment of a differential diagnosis between
      atypical variants of amyotrophic lateral sclerosis ("flail arm" syndrome) and
      primary muscular atrophy of adults at the early stages of the disease. We suppose
      that atypical variants of amyotrophic lateral sclerosis resultant from affection
      of lower motor neuron only ("flail arm" syndrome and distal amyotrophy), could be
      distinguished from amyotrophic lateral sclerosis and considered as an independent
      entity.

PMID- 16457129
TI  - [A transition of a functional disease to an organic psychosomatic disorder].
AB  - Twenty patients with ulcer (83 female and 117 male) have been studied. It was
      found out that many patients had functional disorders of the gastrointestinal
      tract in the form of gastralgia or neurogenic vomiting ("organic neurosis of
      stomach") long before the disease manifestation. At that time the patients
      underwent gastroscopy and X-ray examination of the stomach and the duodenum but
      no pathological organic changes were revealed. The study showed that 13% of men
      and 28% of women with "organic neurosis of the stomach" had signs of ulcer
      disease 12-13 years later. Therefore, a transition of functional to organic
      within unified psychosomatic process is in principle possible.

PMID- 16457130
TI  - [Topamax in preventive therapy of migrene: long-term treatment results].

PMID- 16457131
TI  - [An analysis of subjective perception of hypnotic state].
AB  - The results of the study of hypnotic states on the basis of subjective
      reflections of their perceptions by patients are presented. The factor map of the
      features of hypnotic states formation is obtained and some variants of the course
      of hypnotic states are determined in light of domination of the certain factors.

PMID- 16457133
TI  - [The spectral analysis of the variability of frequency and amplitude
      characteristics of tremor in patients with essential tremor and tremulous form of
      Parkinson's disease].
AB  - A clinical and electrophysiological analysis of tremor in patients with essential
      tremor and tremulous form of Parkinson's disease as well as healthy subjects has
      been conducted. The method of accelerometry was used for assessing the
      variability of frequency and amplitude tremor. A comparison of the time-domain
      characteristics and spectral components of tremor was made between the two groups
      of patients that allowed to find the series of typical characteristics, which
      were important for understanding of its pathogenesis and differential diagnosis
      of this disease.

PMID- 16457132
TI  - [A randomized, double blind, placebo-controlled study of the efficacy and safety
      of tolperisone in spasticity following cerebral stroke].
AB  - To study the efficacy and safety of tolperisone--a centrally acting muscle
      relaxant with membrane stabilizing activity--in the treatment of stroke-related
      spasticity. This was a randomized, double-blind, placebo-controlled, multicenter
      study with parallel groups. Treatment lasted 12 weeks and was started with a
      titration period of variable length (dose range 300-900 mg tolperisone daily).
      The degree of spasticity determined on the Ashworth Scale in the most severely
      affected joint area was denned as primary target parameter. Hundred and twenty
      patients (43 females, 77 males) in a mean age of 63,3 +/- 10,6 years were
      recruited and received treatment. In the majority of patients both limbs of each
      side were affected by the spasticity which on average had been present for 3,3 +/
      4,4 years. A 62% of the patients were treated with a daily dose >600 mg
      tolperisone. Tolperisone reduced the mean Ashworth Score by a mean of 1,03 +/-
      0,71 compared with a mean reduction of 0,47 +/- 0,54 in the placebo group
      (p<0,0001). A 78,3% of the patients on tolperisone versus 45% of the placebo
      patients experienced a reduction by at least 1 point on the Ashworth Scale
      (p<0,0001). Functional and overall assessments of efficacy confirmed superior
      efficacy of tolperisone. Adverse events occurred less often on active treatment
      (n=19) than on placebo (n=26) and were mostly of mild-to-moderate intensity. No
      withdrawals caused by adverse events were reported in the tolperisone group. The
      findings of the present study demonstrate the efficacy and excellent tolerance of
      tolperisone in the treatment of spastic hypertonia following cerebral stroke.
      Study data further suggest that an individual dose titration which may exceed the
      recommended maximum dose of 450 mg daily results in optimized therapeutic
      benefit.

PMID- 16457134
TI  - [A genetic analysis of neurological symptoms in schizophrenic families].
AB  - To investigate an accumulation of certain neurological signs in patients with
      schizophrenia and their relatives and to estimate heritability of neurological
      abnormalities, 95 patients, 169 relatives and 35 healthy subjects have been
      studied using standardized clinical neurological examination. Neurological
      abnormalities in patients and their relatives did not form a constant and
      localized pattern and exerted an influence on various functions. A frequency of
      each symptom, with an exception of autonomic ones, was low both in families and
      controls. A total neurological index as well as generalized indices of 2
      categories of most frequent disorders--motor and autonomic--did not reveal a
      significant genetic determination. Therefore, neurological symptoms detected
      during the clinical neurological examination of the relatives may be considered
      as markers of genetic risk for schizophrenia.

PMID- 16457135
TI  - [Antibodies to acetylcholine receptor in patients with different clinical forms
      of myasthenia and Lambert-Eaton myasthenic syndrome].

PMID- 16457136
TI  - [A possibility of the use of low naloxone dosages in the treatment of heroin
      dependence].

PMID- 16457137
TI  - [Current clinical and instrumental diagnosis of brain death].

PMID- 16457138
TI  - [Speech defects in patients with epilepsy].

PMID- 16457139
TI  - [Pathogenesis of psychological appearances of opioid dependence: a dualistic
      model].

PMID- 16457140
TI  - Proteomic strategies and their application in cancer research.
AB  - The understanding of carcinogenesis and tumor progression on a molecular basis
      needs a detailed study of proteins as effector molecules and as critical
      components of the multiple interconnected signaling pathways that drive the
      neoplastic phenotype. Thus, the proteomic approach represents a powerful tool for
      the challenge of the post-genomic era. The term "cancer proteome" refers to the
      collection of proteins expressed by a given cancer cell and should be considered
      as a highly dynamic entity within the cell, which affects a variety of cellular
      activities. The emerging proteomic analysis platforms including 2D-PAGE, mass
      spectrometry technologies, and protein microarrays represent powerful tools to
      study and understand cancer. These systems aim to not only identify, catalogue,
      and characterize cancer proteins, but also to unveil how they interact to affect
      overall tumor progression. Moreover, recent studies on various cancers have
      reported promising results concerning the detection of novel molecular biomarkers
      useful in the early diagnosis of cancer and in drug discovery. Thus, a new
      subdiscipline named clinical proteomics, concomitant with new molecular
      technologies that are developed, demonstrates promise to discover new cancer
      biomarkers. The early diagnosis of cancer, even in a premalignant state, is
      crucial for the successful treatment of this disease. For these reasons, it is
      clear that the identification of biomarkers for the early diagnosis of cancer
      should represent one of the main goals of this emerging field of study.

PMID- 16457142
TI  - Elderly patients with advanced colorectal cancer: tolerability and activity of
      chemotherapy.
AB  - AIMS AND BACKGROUND: Colorectal cancer is the most common gastrointestinal tumor
      in Western countries and is increasing in elderly patients. In recent years, new
      treatments based on the use of 5-fluorouracil associated with oxaliplatin or CPT
      11 have shown promising activity. The aim of the present study was to analyze the
      tolerability and activity of chemotherapy with 5-fluorouracil plus oxaliplatin or
      CPT-11 in elderly patients with advanced colorectal cancer. METHODS: Patients
      aged 70 years or older with advanced colorectal cancer were treated with 5
      fluorouracil (400 mg/m2 in bolus and 600 mg/m2 in a 22-hr continuous infusion on
      days 1-2) plus folinic acid (100 mg/m2) associated to oxaliplatin (85 mg/m2 on
      day 1, FOLFOX regimen) or CPT-11 (180 mg/m2 on day 1, FOLFIRI regimen), every 14
      days. RESULTS: Twenty-nine patients with a median age of 76 years (range, 70-82)
      were treated with FOLFOX or FOLFIRI as first-line chemotherapy for metastatic
      disease. We observed a partial response in 8/29 (27.6%), stable disease in 11/29
      (37.9%) and progressive disease in 10/29 (34.5%). Median survival was 21 months;
      1-year survival probability was 89.8%. Grade III leukopenia was observed in 2/29
      (7%) patients and grade III diarrhea in 1/29 patients. No other grade III-IV
      toxicity was observed. CONCLUSIONS: FOLFOX and FOLFIRI appear to be active and
      well tolerated regimens for elderly patients with advanced colorectal cancer.

PMID- 16457141
TI  - Localized extranodal lymphoma of the head and neck: retrospective analysis of a
      series of 107 patients from a single institution.
AB  - PURPOSE: To retrospectively analyze the outcome and patterns of relapse in
      localized extranodal non-Hodgkin's lymphoma of the head and neck (HN-NHL) after
      radiotherapy alone or combined modality treatment. PATIENTS AND METHODS: A
      retrospective analysis of 107 patients with HN-NHL was performed. Relapse
      patterns, overall survival (OS) and relapse-free survival (RFS) were analyzed.
      Only stage I (n=50) and stage II (n=57) patients were included with either low
      grade (n=21) or high-grade (n=86) lymphoma. Fifty-nine patients were treated with
      radiotherapy (RT) alone and 48 patients received combined-modality treatment
      (CMT) consisting of chemotherapy (CHOP or CHOP-like) followed by radiotherapy.
      The volumes of irradiation included local field (n=24), involved field (n=13) and
      extended field (n=70). The median age at diagnosis was 63 years (range, 17-86
      years). RESULTS: The overall response rates (CR+PR) in the radiotherapy group and
      the combined modality group were 100% and 96%, respectively. With a median follow
      up of 49.4 months, 29 of 59 patients after RT alone (37%) and 30 of 48 patients
      after CMT (62%) were disease-free. In the whole series the projected five-year OS
      and RFS were 58.7% and 61.8%. At univariate analysis of clinical variables with
      potential impact on survival including age, stage, histology, IPI score, single
      or combined treatment and volumes of irradiation, only age and, to a limited
      extent, type of treatment influenced OS (age < or =60 years 79%, >60 years 41%, P
      < 0.001; RT alone 54.9%, CMT 62.8%, P = 0.0487) and RFS (< or =60 years 75%, >60
      years 50%, P < 0.001; RT alone 54%, CMT 71%, P = 0.039). Better OS and RFS rates
      were obtained in patients with stage II and high-grade disease treated with CMT
      (five-year OS and RFS 63% and 69%, respectively; the corresponding values for RT
      alone were 38% and 34%). The final model of the multivariate analysis retained
      only age (< or =60 years) as a significant prognostic factor for both RFS and OS
      (P < 0.001). In the whole series, the sites of relapse were mainly systemic (n =
      32/40, 80%) and in-field relapses were rare (n = 3/40, 7.5%). CONCLUSION: HN-NHL
      is characterized by a high risk of relapse, particularly at distant sites. Older
      patients have a significantly worse prognosis. Radiotherapy offers a very good
      local control rate although combined modality treatment possibly produces better
      RFS and OS, especially for stage II and high-grade disease. Better systemic
      approaches are warranted for a more consistent impact on survival in this
      particular subset of extranodal lymphoma. However, radiotherapy alone may offer a
      feasible and effective modality for patients who cannot tolerate more aggressive
      treatments. Extended-field radiotherapy and the treatment of a larger number of
      uninvolved lymph nodal regions does not confer a RFS or OS advantage, either
      after RT alone or after CMT.

PMID- 16457143
TI  - Management of patients with gastrointestinal stromal tumors: experience from an
      Italian hospital.
AB  - Gastrointestinal stromal tumors are malignancies originating from
      stromal/mesenchymal tissues, most commonly in the stomach and small intestine,
      although they can be located everywhere in the gastrointestinal tract. Diagnosis
      is based on histological and immunohistochemical examination, and these rare
      tumors are characterized by c-kit (CD117) staining. Complete removal of the tumor
      is often curative in localized gastrointestinal stromal tumors and is always
      recommended. Clinically, their behavior is difficult to predict, and mitotic
      count and tumor size seem to be the most effective prognostic factors. We
      performed a retrospective analysis of clinical presentation and course, surgical
      management and pathological features of patients with gastrointestinal stromal
      tumors treated in our institution from 1995 to 2003. Twenty-two patients were
      enrolled in the study, and all of them underwent surgery. There were two
      perioperative deaths, and global morbidity was about 13%. Nineteen patients were
      followed (mean, 31 months): 4 patients had disease progression/recurrence and
      died, and one patient experienced a local recurrence and was reoperated with a
      curative intent; 14 patients were disease free. Our experience shows that
      histological and immunohistochemical examinations are fundamental for a
      definitive diagnosis and to assess the risk of aggressive behavior. Moreover, our
      results confirm that in stromal tumors complete surgical resection remains the
      mainstay of treatment in localized gastrointestinal stromal tumors, although the
      recurrence rate is relatively high. It is conceivable that treatment and
      prognosis of metastatic and non-resectable gastrointestinal stromal tumors, as
      well as the adjuvant treatment of high-risk, radically excised gastrointestinal
      stromal tumors will be strongly impacted by the c-kit target therapy.

PMID- 16457144
TI  - Adjuvant systemic therapies in patients with colorectal cancer: an audit on
      clinical practice in Italy.
AB  - AIMS AND BACKGROUND: Rarely are conclusions from clinical trials summarized in
      international consensus conferences and promptly transferred to patient care. The
      adjuvant therapy for colorectal cancer used in daily clinical practice in Italy
      is described and compared with the recommendations of the 1990 NIH Consensus
      Conference. PATIENTS AND METHODS: We audited prescriptions of adjuvant systemic
      therapies for Italian colorectal cancer patients in 82 centers during a fixed one
      week period. RESULTS: Among 434 patients receiving adjuvant chemotherapy there
      were 139 (42.5%) colon cancer patients with N- and 169 (51.7%) with N+ regional
      nodal involvement. Treatment at academic centers, a young age, T4 and a low total
      number of lymph nodes removed at surgery were the factors potentially justifying
      the decision for adjuvant chemotherapy in stage II colon cancer patients. The
      most common chemotherapy used was a bolus of 5-fluorouracil/folinic acid for 6
      months (75.8%). Adjuvant radiotherapy was not administered to 37 (38.5%) of 96
      patients with stage II and III rectal cancer. CONCLUSIONS: The study shows that a
      substantial proportion of patients on adjuvant treatment at a certain time point
      in a large enough sample of Italian centers are stage II (potential over
      treatment) and that an under-treatment of stage II and III rectal cancer patients
      (lack of radiotherapy) occurs too often in daily clinical practice in this
      country.

PMID- 16457145
TI  - Low-molecular-weight heparin and calcium heparin in thrombosis prophylaxis in
      patients with percutaneous arterial and venous ports for colorectal liver
      metastases.
AB  - STUDY OBJECTIVE: The evaluation of low-molecular-weight heparin use to prevent
      arterial and venous thrombosis in patients with indwelling arterial Port-a-Cath
      implants. METHODS: From 1996 to March 2003 we placed 370 indwelling hepatic
      arterial catheters with a minimally invasive approach. The left distal subclavian
      artery was approached from beneath the left clavicle, then an angiographic study
      of the tumoral vascular district was performed and the gastroduodenal artery was
      occluded by an embolus. A polyurethane catheter was introduced distally into the
      hepatic artery and connected to a reservoir through a 3-4 cm long subcutaneous
      tunnel. In 90 patients a venous Port-a-Cath was placed for concurrent systemic
      chemotherapy. All 370 patients received regional chemotherapy and were treated
      with calcium heparin at a dose of 5000 IU twice a day and with low-molecular
      weight heparin at prophylactic doses (dalteparin 2500 IU or nadroparin 3000 IU)
      during catheter permanence to prevent hepatic artery thrombosis. Intra-arterial
      trans-port radionuclide scans using technetium-99m-labeled micro-aggregated
      albumin were performed monthly to check the infusion distribution and hepatic
      artery patency. In the presence of anomalous patterns, thrombosis, pulmonary
      embolism or other complications, angiography and/or other diagnostic studies were
      performed to determine the cause of the vascular event and the local or systemic
      symptoms. The mean arterial and venous Port-a-Cath permanence times were 6 and 8
      months, respectively. RESULTS: We observed episodes of hepatic artery thrombosis
      in 4.3% of patients. Three of these 17 patients were successfully treated by
      intra-arterial thrombolysis using urokinase. No venous thrombosis occurred as a
      consequence of regional and/or systemic chemotherapy, no episodes of arterial
      thrombosis were registered during arterial catheter permanence, nor did any
      hemorrhagic complications related to anti-coagulant therapy occur. Five patients
      treated with low-molecular-weight heparin required treatment suspension due to a
      platelet count of < 40,000/dL. CONCLUSION: Our experience suggests that low
      molecular-weight heparin and/or calcium heparin at prophylactic doses could be
      useful in the prevention of arterial and venous thrombosis in patients with
      indwelling arterial catheters or venous Port-a-Cath treated with regional or
      systemic chemotherapy for hepatic metastases from colorectal cancer. The
      homogeneity of the patient group and the use of analogous chemotherapeutic drugs
      (fluoropyrimidines) avoided statistical contamination related to differences
      between kinds of cancer and between the chemotherapeutic agents used.

PMID- 16457146
TI  - Recurrence of pseudomyxoma peritonei within the inguinal canal.
AB  - AIM AND BACKGROUND: Tumor appearing in an inguinal hernia sac indicates
      widespread carcinomatosis with ascites. A new onset hernia is a common clinical
      presentation of pseudomyxoma peritonei syndrome arising in an appendiceal
      mucinous tumor. Recurrence of pseudomyxoma peritonei within the inguinal region
      was previously reported in only a single patient. We present five patients with a
      recurrence of pseudomyxoma peritonei tumor nodules in the inguinal region
      following cytoreductive surgery and attempt to understand the etiology of this
      treatment failure. METHODS AND STUDY DESIGN: From a database of 910 patients with
      mucinous appendiceal tumors with peritoneal dissemination who had definitive
      treatment, five patients who had disease recurrence within the inguinal region
      were identified. The clinical histories were studied and presented in order to
      make future recommendations regarding the management of these patients. RESULTS:
      Five patients with ages ranging 39 to 67 years had a mucinous tumor in the
      inguinal region as a recurrence after a previous cytoreductive surgery combined
      with perioperative intraperitoneal chemotherapy. One of them had separate
      recurrence in both right and left inguinal regions. All these patients were made
      disease-free by the reoperative surgery with a sacrifice of the testicle in four.
      None have evidence of a recurrence of an inguinal hernia despite the lack of
      formal repair. CONCLUSION: At the time of initial cytoreductive surgery the
      surgeon should be aware of the inguinal region as a possible site of relapse.
      This may be more problematic in patients who have had prior surgery with mucoid
      fluid in a hernia as the presenting sign of pseudomyxoma peritonei. Inguinal
      recurrences should be removed with clear margins even if orchiectomy is required.

PMID- 16457147
TI  - Liver resection for intrahepatic cholangiocarcinoma.
AB  - AIMS AND BACKGROUND: Intrahepatic cholangiocarcinoma (IHCC) is the second most
      common primary liver cancer, representing 10% of all primary liver malignancies.
      Despite the increase in its incidence, this tumor remains extremely rare in
      Western countries and few reports detailing experience with surgical resection
      have been published. The aim of this study was to analyze the experience with
      resection of IHCC in our center. METHODS: From 1987 to 2003 we observed 35
      patients with IHCC; 15 of them (42.8%) were submitted to hepatic resection. IHCCs
      accounted for 13% of all liver resections for primary liver tumors carried out at
      our center during this period. According to the classification of the Liver
      Cancer Study Group of Japan, the tumors were classified as "mass-forming" in 14
      cases and as "periductal" in one case. Major resections were performed in ten
      cases and minor resections in five cases. In the patient with a periductal tumor
      a major resection was performed along with excision of the main biliary
      confluence. In 14 cases (93.3%) tumor-free resection margins were obtained.
      RESULTS: The intraoperative mortality was nil and the postoperative mortality
      6.6%. The postoperative morbidity rate was 21.4%. The mean overall survival was
      38.4 months, with 86% and 49% one- and three-year survival rates, respectively.
      Patients with mass-forming tumors and curative resections (R0) (mean survival
      40.8 months; one- and three-year survival rates 92.3% and 52.7%), and those with
      TNM stage I-II tumors (mean survival 43.7 months; one- and three-year survival
      rates 100% and 66.7%) had a longer survival. The patient with the periductal
      tumor and R1 resection died after seven months. CONCLUSIONS: These results
      support a surgical approach based on accurate selection of patients with IHCC and
      aimed at radical resection whenever possible. The good survival rates observed in
      R0 resections emphasize the role of radical surgery as the only chance of cure
      for patients with this tumor.

PMID- 16457148
TI  - Postoperative chemoradiotherapy of pancreatic cancer: what is the appropriate
      target volume of radiation therapy?
AB  - AIMS AND BACKGROUND: To evaluate the influence of radiation therapy target volume
      on the treatment outcome of adjuvant chemoradiotherapy for pancreatic cancer
      after curative resection. METHODS: Between February 1987 and July 2001, 70
      patients treated with curative resection and adjuvant chemoradiotherapy for
      pancreatic adenocarcinoma were analyzed. There were 49 males and 21 females, with
      a median age of 57 years. Whipple's operation was performed in 44 patients,
      pylorus-preserving pancreaticoduodenectomy in 14, distal pancreatectomy in 9, and
      subtotal pancreatectomy in 3. Postoperative adjuvant radiotherapy was given up to
      40 Gy at 2 Gy per fraction with a two-week planned rest. Intravenous 5
      fluorouracil (500 mg/m2/day) was given on days 1 to 3 of each split course of
      radiotherapy. Until 1991, whole pancreas or preoperative tumor volume and
      retroperitoneal lymph nodes were irradiated (extended field, n=14). Thereafter,
      the target volume included the retroperitoneal lymph nodes and the involved
      pancreatic resection margin (limited field, n=56). The median follow-up period of
      all the patients was 16 months (range, 2-99). RESULTS: The overall 2- and 5-year
      survival rate of all patients was 29.7% and 14.0%, respectively. According to the
      radiotherapy target volume, the median survival time was 14 months in the
      extended field group and 16 months in the limited field group (P = 0.65).
      CONCLUSIONS: From the viewpoint of the target volume of radiotherapy, a limited
      field did not worsen the treatment outcome, although the survival rate was poor
      in both groups.

PMID- 16457149
TI  - Raltitrexed and radiotherapy as adjuvant treatment for stage II-III rectal
      cancer: a feasibility study.
AB  - AIMS AND BACKGROUND: Adjuvant 5-FU chemotherapy plus radiotherapy represents the
      standard treatment for radically resected rectal cancer at high risk of relapse
      according to the NIH Consensus Conference. The therapeutic gain was obtained with
      a high rate of severe treatment-related toxicity and a suboptimal patient
      compliance with this regimen. Raltitrexed is a specific thymidylate synthase
      inhibitor with a convenient administration schedule, acceptable toxicity and
      radiosensitizing properties, as the published phase I trials in combination with
      radiotherapy have shown. The aim of this prospective multicenter phase II study
      was to evaluate the feasibility, gastrointestinal and hematological acute
      toxicity of raltitrexed in combination with radiotherapy in rectal cancer
      patients. METHODS: From September 2000 to June 2004, 50 patients with radically
      resected stage II-III rectal adenocarcinoma were treated. All patients were
      evaluable for compliance and acute toxicity. Within 45-60 days of surgery, each
      patient underwent concomitant adjuvant radiochemotherapy. Radiotherapy was
      administered to the pelvis (plus perineum after abdominoperineal resection) with
      photon beam energy exceeding 5 MV, 3-4 fields, 45 Gy/25 fractions/5 weeks plus a
      boost delivered to the site of resected disease with 3-4 fields, 9 Gy/5
      fractions/1 week to a total dose of 54 Gy. The boost dose was administered after
      complete exclusion of the small bowel from the treatment volumes; if this was not
      possible a total dose of 50.4 Gy was given. Raltitrexed was administered
      intravenously at a dose of 3 mg/m2 as a bolus injection on days 1 and 22 of
      radiotherapy one hour before treatment, for a total of two cycles. Each patient
      underwent weekly clinical evaluation and laboratory tests. Toxicity was assessed
      by the WHO scale. RESULTS: Forty-five (90%) patients completed the established
      treatment. Acute severe toxicity included grade III proctitis in 4/50 (8%), grade
      III-IV diarrhea in 4/50 (8%), grade III perineal dermatitis in 4/50 (8%) and
      grade III leukopenia in 2/50 (4%) patients; five patients (10%) experienced a
      transient grade Ill increase in their liver biochemistry values. CONCLUSIONS: Our
      data related to acute toxicity and patient compliance proved the feasibility of
      this adjuvant radiochemotherapy treatment. A longer follow-up is necessary to
      evaluate the effectiveness of this new regimen in terms of disease-free and
      overall survival.

PMID- 16457150
TI  - Molecular profile and clinical variables in BRCA1-positive breast cancers. A
      population-based study.
AB  - PURPOSE: To evaluate the clinical features of breast cancer patients with genetic
      susceptibility to this disease and to investigate the contribution of BRCA1
      germline mutations to the phenotype of these tumors. PATIENTS AND METHODS: We
      reviewed the clinical and pathological records of 102 women with suspected
      inherited susceptibility to breast cancer consecutively seen at the Genetic
      Oncology Service of Parma, Italy. Sixty-two patients with a high probability of
      harboring a germline, cancer-predisposing mutation were tested for BRCA1
      mutations. Exon 11 was screened using the protein truncation test and detected
      mutations were confirmed by direct sequencing (DS). All other exons were analyzed
      by DS. RESULTS: Among the 62 patients with a completed mutation analysis, 48
      (77.4%) had wild-type BRCA1, six (9.6%) had variants of unclear significance,
      eight (13%) had deleterious mutations. BRCA1-associated breast cancers (BABC)
      were significantly less likely to be diagnosed at stage I than breast cancers in
      women without mutations (12.5% vs 51%; P = 0.045), more likely to have a high
      proliferation rate (100% vs 24%, P < 0.001), and more likely to be histological
      grade 3 (100% vs 14%, P < 0.001), estrogen and progesterone receptor negative
      (87.5% vs 13%, P < 0.001; 75% vs 23%, P = 0.004), and p53 positive (87.5% vs 30%,
      P = 0.023). All tumors with BRCA1 mutations were HER-2/neu negative compared with
      57% of the non-BRCA1 tumors (P = 0.04). There were no significant differences
      between BABC and non-BABC in 20-year relapse-free survival, 20-year event-free
      survival, and 20-year overall survival. CONCLUSION: In this population-based
      study, BABC seems to present with adverse molecular features when compared with
      non-BABC, although the prognosis appears to be similar.

PMID- 16457151
TI  - Potential prognostic significance of p185(HER2) overexpression with loss of PTEN
      expression in gastric carcinomas.
AB  - AIMS AND BACKGROUND: The HER2 gene encodes a 185-kd transmembrane glycoprotein
      receptor (p185(HER2)) that has partial homology with the epidermal growth factor
      receptor and shares intrinsic tyrosine kinase activity. The phosphatase and
      tensin homolog mutated on chromosome ten (PTEN) gene product is a protein
      tyrosine phosphatase that participates in modulating the phosphoinositide 3
      kinase pathway which has antagonizing activity to protein tyrosine kinase. The
      authors investigated the correlation between clinicopathologic variables
      including survival and the overexpression of the p185(HER2) with loss of PTEN
      expression in gastric adenocarcinoma patients. METHODS: The protein expression of
      p185(HER2) and PTEN was examined by immunohistochemical stain in paraffin
      embedded tissues of 94 (M:F, 52:42) gastric adenocarcinoma patients by using
      monoclonal antibody, and the results were related to clinicopathological
      variables and survival. RESULTS: p185(HER2) overexpression correlated positively
      with lymph node metastasis, distant metastasis, AJCC classification, higher
      relapse rate. Patients with overexpression of p185(HER2) were found to have
      significantly lower disease-free survival (P = 0.003) and overall survival (P =
      0.0004). Loss of PTEN expression correlated positively with depth of invasion (T
      stage) and was more frequent in the advanced stage. The patient group with
      p185(HER2) overexpression and loss of PTEN expression showed significantly
      shorter disease-free and overall survival (P = 0.03, P = 0.01) than the other
      groups. CONCLUSIONS: Our observations suggest potential prognostic significance
      of p185(HER2) overexpression with PTEN loss in gastric adenocarcinoma patients.
      This opens up the possibility of considering p185(HER2)and PTEN as a therapeutic
      target in gastric cancer.

PMID- 16457152
TI  - Serum markers and prognosis in locally advanced breast cancer.
AB  - BACKGROUND: Locally advanced breast cancer (LABC) represents a heterogeneous
      subgroup of breast cancer with an often dismal outcome. Identifying prognostic
      factors has acquired great significance for the selection of optimal treatment in
      individual patients. METHODS: Between January 1993 and December 1997, 103
      patients were treated in our institution with multimodality treatment consisting
      of neoadjuvant chemotherapy followed by surgery, adjuvant chemotherapy and
      radiotherapy; tamoxifen was added in hormone receptor-positive cases. In the
      search for prognostic factors well-established parameters (clinical, pathological
      and treatment-related) as well as new features with potential value (c-erbB-2,
      baseline serum levels of CA 15.3 and CEA) were included in the univariate and
      multivariate analysis. RESULTS: At a median follow-up of 92 months (range, 8
      130), the estimated five-year cancer-specific overall survival (OS) and disease
      free survival (DFS) were 71.34% and 57.7%, respectively. Among the 22 different
      variables studied, only 10 were significantly correlated with OS and DFS. In
      multivariate analysis five retained independent prognostic value for both OS and
      DFS: tumor grade, serum markers, features of inflammatory breast cancer (IBC),
      response to neoadjuvant chemotherapy and lymph node status. With cutoff values of
      35 U/mL for CA 15.3 and 5 ng/mL for CEA, the probability of five-year OS (Cox
      hazard ratio 3.91, P = 0.0009) and DFS (Cox hazard ratio 2.40, P = 0.02)
      decreased from 78% to 52% and from 68% to 47%, respectively, when at least one of
      these markers was abnormal. CONCLUSIONS: Baseline serum levels of CEA and CA 15.3
      emerged from this study as strong independent predictors of outcome in LABC,
      whose value adds to other established prognostic factors such as postoperative
      nodal status, IBC, histological grade and response to neoadjuvant chemotherapy.

PMID- 16457153
TI  - Fusion hybrid of dendritic cells and engineered tumor cells expressing
      interleukin-12 induces type 1 immune responses against tumor.
AB  - AIMS AND BACKGROUND: Dendritic cell (DC)-tumor fusion hybrid vaccinees that
      facilitate antigen presentation represent a novel powerful strategy in cancer
      immunotherapy. Preclinical studies have demonstrated that IL-12 promotes specific
      antitumor immunity mediated by T cells in several types of tumors. In the present
      study, we investigated the antitumor immunity derived from vaccination of fusion
      hybrids between DCs and engineered J558/IL-12 myeloma cells secreting Th1
      cytokine IL-12. METHODS: The expression vector pcDNA-IL-12 was generated and
      transfected into J558 myeloma cells and then bone marrow-derived DCs were fused
      with engineered J558/IL-12 cells. The antitumor immunity derived from vaccination
      of the fusion hybrid DC/J558/IL-12 was evaluated in vitro and in vivo. RESULTS:
      DC/J558/IL-12 cells secreted recombinant IL-12 (1.6 ng/mL), and inoculation of
      BALB/c mice with DC/J558/IL-12 hybrid induced a Th1 dominant immune response and
      resulted in tumor regression. Immunization of mice with engineered DC/J558/IL-12
      hybrid elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL)
      responses in vitro as well as more potent protective immunity against J558 tumor
      challenge in vivo than immunization with the mixture of DCs and J558/IL-12,
      J558/IL-12 and J558, respectively. Furthermore, the anti-tumor immunity mediated
      by DC/J558/IL-12 tumor cell vaccination in vivo appeared to be dependent on CD8+
      CTL. CONCLUSIONS: These results demonstrate that the engineered fusion hybrid
      vaccines that combine Th1 cytokine gene-modified tumor cells with DCs may be an
      attractive strategy for cancer immunotherapy.

PMID- 16457155
TI  - Upregulation and overexpression of DVL1, the human counterpart of the Drosophila
      dishevelled gene, in prostate cancer.
AB  - AIMS AND BACKGROUND: The Wnt/beta-catenin signaling pathway is one of the main
      carcinogenic mechanisms in human malignancies including prostate cancer.
      Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta
      catenin signaling pathway. In addition, alterations of the DVL1 gene have been
      reported in breast and cervical cancer. The abnormality of beta-catenin in
      prostate cancer has been well studied, so the examination of the DVL1 gene in
      prostate cancer is appealing. METHODS: We investigated DVL1 messenger RNA
      alterations by semiquantitative PCR (SQ-PCR) in 20 primary prostate cancers and
      assessed the protein expression by immunohistochemical analysis in the same
      samples. In addition, DVL1 and beta-catenin protein expression was evaluated with
      a new validated set of 20 prostate cancers. RESULTS: SQ-PCR revealed significant
      overexpression of DVL1 in prostate cancer (65%). Upregulation of the DVL1 gene
      product in prostate cancer was confirmed by immunostaining. With SQ-PCR and
      immunostaining, none of the cases showed underexpression or downregulation of
      DVL1. In addition, the data showed correlations between DVL1 mRNA and protein
      expression. Interestingly, the expression level of DVL1 increased with worsening
      histological grade. In addition, a correlation between DVL1 expression and beta
      catenin expression was confirmed. CONCLUSIONS: DVL1 was overexpressed in prostate
      cancer and its overexpression might be related to prostate cancer progression
      through the Wnt/beta-catenin pathway.

PMID- 16457154
TI  - BAG-1 expression in hyperplastic and neoplastic prostate tissue: is there any
      relationship with BCL-related proteins and androgen receptor status?
AB  - AIMS AND BACKGROUND: To evaluate the function and distribution of BAG-1 protein
      in hyperplastic and neoplastic prostate tissue and establish the relationship
      between this protein and BCL-related proteins (BCL-2 and BAX), androgen receptor
      (AR) expression and chromogranin A. METHODS: Twenty-eight prostatic
      adenocarcinomas and 16 prostate hyperplasias were included in this retrospective
      study. BAG-1, BCL-2, BAX, androgen receptor and chromogranin A immunostaining was
      performed by means of standard avidin-biotin peroxidase methods. The M30 antibody
      was used to identify preapoptotic and apoptotic cells. The immunohistochemical
      histological score (HSCORE) semiquantative system was used to evaluate
      immunohistochemical staining. RESULTS: Statistical analysis showed a significant
      difference in HSCOREs of BAX, M30 and AR between the carcinoma and hyperplasia
      groups. Carcinomas expressed higher HSCOREs of these markers than hyperplasias.
      There were significant differences in nuclear and cytoplasmic BAG-1 positivity
      between high and low-grade carcinomas. BAG-1 expression was higher in low-grade
      carcinomas. In the carcinoma group there was a positive correlation (Pearson)
      between BCL-2 and cytoplasmic/nuclear BAG-1. In the hyperplasia group there was a
      negative correlation between BAX and BCL-2, and between AR and M30. We also
      detected a positive correlation between AR and nuclear/cytoplasmic BAG-1 and
      between nuclear and cytoplasmic BAG-1 in hyperplasias. BAG-1 showed the same
      specific basal cell localization as BCL-2 in hyperplastic and normal glands.
      CONCLUSIONS: The BAG-1 protein showed a distinct distribution pattern in
      hyperplastic and neoplastic prostate. BAG-1 in association with BCL-2 inhibits
      apoptosis and may prolong the life of neoplastic cells and give them a chance to
      gain new oncogenic features in early carcinogenesis.

PMID- 16457157
TI  - Adolescent renomedullary interstitial cell tumor: a case report.
AB  - A 14-year-old boy presented with painless gross hematuria after a blunt trauma to
      his right lumbar region. Abdominal ultrasonography and abdominal computerized
      tomography revealed that the right kidney was hydronephrotic; contrast material
      delineated a hematoma inside the kidney. The patient underwent a right simple
      nephrectomy and after histopathological examination was found to have a
      renomedullary interstitial cell tumor of the right kidney. This tumor is common
      in patients older than 50 years, whereas our patient was very young. The
      diagnosis of this small tumor is not possible by conventional radiological
      techniques and histopathological examination is mandatory for its diagnosis.

PMID- 16457156
TI  - Mesenteric fibromatosis in a patient with Camurati-Engelmann disease. A case
      report and literature review.
AB  - Mesenteric fibromatosis is a rare type of desmoid tumor characterized by local
      aggressiveness and a tendency to relapse. In view of these characteristics it may
      be considered a low-grade fibrosarcoma. Camurati-Engelmann disease is a very rare
      form of bone dysplasia characterized by osteosclerosis of the diaphyses of the
      long bones. Here we describe the case of a male patient affected by these two
      rare diseases in association with chronic inflammatory intestinal disease.

PMID- 16457158
TI  - Parathyroid carcinoma in a chronic hemodialysis patient: case report and review
      of the literature.
AB  - Parathyroid carcinoma is a rare disease in normal population as well as in
      patients with end-stage renal disease. Approximately 700 cases have been reported
      and, of these, 20 occurred in patients receiving chronic hemodialysis. We
      describe a case of parathyroid carcinoma in a 59-year-old female patient with end
      stage renal disease secondary to membranous glomerulonephritis treated by
      hemodialysis since 1995. In September 1998, the calcium level was 12.4 mg/dl and
      intact parathyroid hormone serum levels were 1366 pg/ml (normal range, 25-65). A
      routine ultrasonographic examination of the neck revealed enlargement of two
      parathyroid glands, the left inferior gland being the largest and measuring 2x3x2
      cm. In October 1998, resection of two parathyroid glands was performed. On the
      basis of histology, which documented the presence of proliferating cells arranged
      in sheets or in a trabecular pattern, numerous mitosis and vascular invasion, a
      diagnosis of parathyroid carcinoma was made.

PMID- 16457159
TI  - Endodermal sinus tumor of the omentum: case report.
AB  - We report a case of primary endodermal sinus tumor of the omentum in a 46-year
      old woman. The patient had been referred to our hospital for pain in the right
      abdomen. CT scan revealed a right-sided abdominal mass. At laparotomy, a large
      omental tumor extending to the bowel, uterus, ovaries and peritoneum was found,
      and it was totally resected. The tumor displayed the typical histological
      patterns observed in endodermal sinus tumor, and the immunohistochemical findings
      confirmed the diagnosis. Serum AFP level was 21.550 ng/ml prior to laparotomy,
      and decreased to 13.845 ng/mL after surgery, whereas the level of serum beta
      human chorionic gonadotropin was normal. Post-surgery, the patient received
      combination chemotherapy consisting of cisplatin, etoposide and bleomycin every 3
      weeks for a total of 6 cycles. At the end of the treatment, all the findings,
      including AFP level, were normal.

PMID- 16457160
TI  - Abstract S7, published in "I Supplementi di Tumori", Vol 4, No 5.

PMID- 16457161
TI  - [Cost effectiveness analysis of two adjuvant regimens in the treatment of
      colorectal cancer: an interpretation of the MOSAIC Study].

PMID- 16457162
TI  - [Docetaxel and novel strategies in the treatment of NSCLC].

PMID- 16457164
TI  - Bayes window (1).

PMID- 16457163
TI  - [Zoledronic acid and osseous pathologies in the course of neoplasia. Part II].

PMID- 16457165
TI  - Perception time measured with the slope-transition paradigm (STP): category, set
      size, and task manipulations.
AB  - A perception time measure was obtained with the 'slope-transition paradigm'
      (STP), which is described in detail. In two experiments with the paradigm,
      participants viewed two sequential data frames, each presented for a wide range
      of durations. They made a binary response based on combined information from the
      two frames. The results showed piecewise linear response-time versus frame
      duration functions with a slope-0 branch at short durations, followed by a slope
      1 branch. The duration where the two branches met (the slope transition) was
      interpreted as the end of the perception of frame 1. For longer durations, the
      participant had completed the perception of frame 1 and was forced to waste time
      waiting for data from frame 2. In experiment 1, an odd-digit enumeration task was
      used, and set size and distractor category (even digits versus consonants) were
      varied. In experiment 2, a same/different task with digits was used and the type
      of judgment (literal versus parity) was varied. Perception time increased with
      set size. Distractor category and judgment type affected post-perceptual
      processes. The perception time measure of the STP is considered in relation to
      the attentional blink, repetition blindness, and object files.

PMID- 16457166
TI  - New illusions of sliding motion in depth.
AB  - Apparent sliding motion in the so-called Ouchi illusion has been attributed to
      the global integration of local motion vectors arising from the aperture effect
      (Fermuller et al, 2000 Vision Research 40 77- 96; Mather, 2000 Perception 29 721
      727). In a number of variants of the Ouchi illusion, we here demonstrate that
      sliding motion will also arise without a directional motion bias from local
      elements. Specifically, we show that in a disk-annulus pattern made from wiggly
      lines, sliding motion occurs although the local orientations within the disk and
      annulus are the same. We then argue that in an array of square-shaped checks,
      sliding motion originates from the interaction between the explicit orientation
      of the checks and the implicit orientation of the invisible diagonals. Finally,
      we demonstrate that a central array of filled black circles surrounded by a grey
      edge appears to slide relative to a surround of empty circles. We tentatively
      account for sliding motion in this figure by differences in speed signals, figure
      ground segregation and apparent depth due to contrast polarity, edge blur,
      demarcation by a frame, and difference in shape.

PMID- 16457167
TI  - The role of facial attractiveness and facial masculinity/femininity in sex
      classification of faces.
AB  - We tested whether adults (experiment 1) and 4 - 5-year-old children (experiment
      2) identify the sex of highly attractive faces faster and more accurately than
      not very attractive faces in a reaction-time task. We also assessed whether
      facial masculinity/femininity facilitated identification of sex. Results showed
      that attractiveness facilitated adults' sex classification of both female and
      male faces and children's sex classification of female, but not male, faces.
      Moreover, attractiveness affected the speed and accuracy of sex classification
      independently of masculinity/femininity. High masculinity in male faces, but not
      high femininity in female faces, also facilitated sex classification for both
      adults and children. These findings provide important new data on how the facial
      cues of attractiveness and masculinity/femininity contribute to the task of sex
      classification and provide evidence for developmental differences in how adults
      and children use these cues. Additionally, these findings provide support for
      Langlois and Roggman's (1990 Psychological Science 1 115 121) averageness theory
      of attractiveness.

PMID- 16457168
TI  - The influence of exploration mode, orientation, and configuration on the haptic
      Muller-Lyer illusion.
AB  - We studied the impact of manner of exploration, orientation, spatial position,
      and configuration on the haptic Muller-Lyer illusion. Blindfolded sighted
      subjects felt raised-line Muller-Lyer and control stimuli. The stimuli were felt
      by tracing with the index finger, free exploration, grasping with the index
      finger and thumb, or by measuring with the use of any two or more fingers. For
      haptic judgments of extent a sliding tangible ruler was used. The illusion was
      present in all exploration conditions, with overestimation of the wings-out
      compared to wings-in stimuli. Tracing with the index finger reduced the magnitude
      of the illusion. However, tracing and grasping induced an overall underestimation
      of size. The illusion was greatly attenuated when stimuli were felt with the
      index fingers of both hands. Illusory misperception was not altered by the
      position in space of the Muller-Lyer stimuli. No effects of changes in the
      thickness of the line shaft were found, but there were effects of the length of
      the wing endings for the smaller, 5.1 cm stimuli. The theoretical and practical
      implications of the results are discussed.

PMID- 16457169
TI  - Watercolor illusion induced by synesthetic colors.

PMID- 16457170
TI  - Bacterial community changes with N'-N' dimethylforamide (DMF) additives during
      polycyclic aromatic hydrocarbons (PAH) biodegardation.
AB  - This study examined the changes in the bacterial community during biodegradation
      of polycyclic aromatic hydrocarbon (PAH) substrate when N'-N' dimethylformamide
      (DMF) was added. The microbial populations that biodegrade the PAH substrate were
      assessed by Fluorescence in-situ hybridization (FISH) and changed from 49.45%
      Archaea and 49.15% Bacteria to 42.00% Archaea and 51.78% Bacteria when the PAH
      was supplemented with DMF. Nine microorganisms were classified as Gram-negative
      alpha-, beta- and gamma-Proteobacteria bacteria during biodegradation of PAH
      alone by the Biolog system. Incentive eleven microorganisms obtained from the PAH
      DMF mixed substrate were found to be beta-, gamma-Proteobacteria bacteria, high
      G+C Gram-positive bacteria (HGC), low G+C Gram-positive bacteria (LGC) and there
      was even one Deinococcus-Thermus strain; this indicates greater biodiversity. The
      numbers in the Pseudomonad group were as high as 10(5)-10(6) CFU ml(-1),
      suggesting that this group plays an important role in PAH biodegradation.
      Community-Level Physiological Profiling (CLPP) and physiological characterization
      were different in the PAH biodegradation process with and without DMF.
      Utilization of the 95 carbon sources from the Biolog GN2 microtiter plate was
      greater during PAH biodegradation when PAH is present alone compared to that in
      the presence of DMF. The range of enzymatic activities during PAH biodegradation
      was lower in the presence of DMF. These results show that DMF should be used with
      caution when PAH is a substrate during laboratory or pilot biotreatability
      studies.

PMID- 16457171
TI  - Adsorption of nickel from aqueous solution by coir based adsorbent, puresorbe.
AB  - The effectiveness of adsorption for nickel removal from wastewater had made it an
      ideal alternative to other expensive treatment options. This paper deals with an
      investigation on coir based adsorbent (Puresorbe) in the removal of nickel from
      the aqueous solutions. The adsorption of nickel was carried out by varying the
      parameters such as agitation time, metal concentration, adsorbent dose,
      temperature and pH. The experimental isotherm data were analyzed using the
      Langmuir and Freundlich isotherms. Adsorption followed a second order rate
      expression for the particle size 250-500 microm at pH 6. The monolayer adsorption
      capacity was 15.31 mg nickel per gram of puresorbe. Thermodynamic parameters show
      the endothermic nature of nickel adsorption. A desorption study carried out using
      distilled water adjusted to pH of 2-10, suggests that ion exchange might be the
      mode of adsorption.

PMID- 16457172
TI  - Adsorption of divalent copper, zinc, cadmium and lead ions from aqueous solution
      by waste tea and coffee adsorbents.
AB  - The adsorption of the divalent cations of Cu, Zn, Cd and Pb by tea leaves and
      coffee grounds from aqueous solutions is described. Both adsorbents exhibited
      strong affinity for these ions which could be described by a simple single-site
      equilibrium model. For coffee, the order of increasing adsorption equilibrium
      constant K was Cu < Pb < Zn < Cd, while for tea the opposite order was observed
      indicating that the adsorption sites on each adsorbent have a different chemical
      nature. Adsorption decreased at low pH < 4 through competition with H+ for
      adsorption sites, and for all metals except Cu, at high pH > 10, probably because
      of anion formation in the case of Zn2+ and also increased leaching of metal
      binding soluble materials. The effect of metal ion concentration on the
      adsorptive equilibria indicated a threshold concentration above which overall
      adsorption became limited by saturation of the adsorption sites. Competition
      between two metal ions for the same sites was not observed with Cu(II) and
      Pb(II), however Zn(II) reacted competitively with Cd(II) binding sites on both
      tea and coffee. If fresh coffee or tea adsorbents were used, the fraction of
      metal ion taken up by the adsorbent was diminished by the competitive effects of
      soluble metal-binding ligands released by the tea or coffee. Experiments with
      coffee showed that roasting temperature controls the formation of metal ion
      adsorption sites for this adsorbent.

PMID- 16457174
TI  - Biomass characterization of laboratory-scale thermophilic-mesophilic wastewater
      treatment processes.
AB  - Two thermophilic-mesophilic wastewater treatment processes, one as the
      combination of the thermophilic activated sludge process (ASP), followed by the
      mesophilic ASP and the other as thermophilic suspended carrier biofilm process
      (SCBP), followed by the mesophilic ASP, were used to study sludge characteristics
      and floc formation. Thermophilic bacteria in both ASP and SCBP were able to form
      flocs, which were <50 microm in size and had a weak structure and irregular
      shape. Flocs in both the mesophilic ASPs were larger in size (50-500 microm) and
      had more compact structures. Filamentous bacteria played an important role in
      both the thermophilic and mesophilic processes by forming bridges between small
      flocs. Both thermophilic processes showed a high density of dispersed particles,
      such as free bacteria. When hydraulic retention time (HRT) was decreased the
      biofilm was retained in the thermophilic SCBP better than the flocs in the
      thermophilic ASP. The mesophilic ASPs efficiently removed dispersed particles
      originating from the thermophilic processes.

PMID- 16457173
TI  - Attenuation of aqueous benzene in soils under saturated flow conditions.
AB  - The fate of aqueous benzene in subsurface was investigated in this study,
      focusing on the role of sorption and biodegradation on the benzene attenuation
      under dynamic flow conditions. Two sets of column tests were conducted in
      Plexiglass flow cells packed uniformly with sandy aquifer materials. The first
      set of the experiment was conducted with a step-type injection of benzene with
      different powder activated carbon (PAC) contents: (1) PAC = 0 %; (2) PAC = 0.5 %;
      (3) PAC = 2.0%. The second set was performed as a pulse-type with different test
      conditions: (4) benzene; (5) benzene and bacteria (Pseudomonas aeruginosa); (6)
      benzene and bacteria (P. aeruginosa) with hydrogen peroxide. In addition,
      numerical experiments were performed to examine the role of sorption processes on
      the benzene attenuation. In the step mode experiments, the KCl breakthrough
      curves (BTCs) reached the input concentration while the benzene BTCs were
      considerably lower than those of KCl with slight retardation for all cases,
      indicating that both reversible/retardation and irreversible sorption occurred.
      The pulse type tests showed that attenuation of benzene increased in the presence
      of bacteria due to biodegradation. The benzene attenuation by microbial
      degradation increased furthermore in the presence of hydrogen peroxide owing to
      sufficient supply of dissolved oxygen in soil column. Numerical experiments
      demonstrated that retardation could not contribute to the attenuation of benzene
      in soils but could only extend its breakthrough time. Experimental results
      indicated that aqueous benzene could be attenuated by irreversible sorption and
      biodegradation during transport through the subsurface. Additionally, the
      attenuation of aqueous benzene is closely related to organic carbon content and
      oxygen level existing in contaminated aquifers.

PMID- 16457175
TI  - Removal of copper (II) from aqueous solutions by flotation using polyaluminum
      chloride silicate (PAX-XL60 S) as coagulant and carbonate ion as activator.
AB  - Flotation is a separation technology for removing toxic heavy metal ions from
      aqueous solutions. Here a simple and rapid flotation procedure is presented for
      the removal of copper(II) from aqueous solutions. It is based on the use of
      polyaluminum chloride silicate (PAX-XL60 S) as coagulant and flocculent,
      carbonate ion as activator and oleic acid (HOL) as surfactant. Both ion and
      precipitate flotation are included depending on the solution pH. Ion and
      precipitate flotation in the aqueous HOL-PAX-XL60 S-Cu2+-CO3(2-) system gave
      powerful preferential removal of Cu2+ (F -100%) over the HOL-PAX-XL60 S-Cu2+
      system containing no CO3(2+) ion (F approximately 86%). The role of CO3(2-) ion
      is also evident from decreasing the dose of PAX-XL60 S from 700 mg l(-1) to 200
      mg l(-1). The other parameters, influencing the flotation process, namely: metal
      ion, surfactant and PAX-XL60 S concentrations, ionic strength, temperature and
      foreign ions were examined. Moreover, the procedure was successfully applied to
      recover Cu2+ ions from different volumes up to 11 and from natural water samples.

PMID- 16457176
TI  - Fluorescent in situ hybridization (FISH) for the detection of bacterial community
      in activated sludge from textile factories.
AB  - Conventional methods used to study the bacterial community structure in activated
      sludge are not sufficient enough to determine the compositions of the bacterial
      populations responsible for biodegradation. Activated sludge samples from 3
      textile factories were analyzed by fluorescent in situ hybridization (FISH) using
      rRNA probes and by phase-contrast microscopy. In Factory-I, the predominant
      groups were the beta-subclass of Proteobacteria and the cytophaga-flavobacterium
      (CF) cluster (33.3% and 31.0%) followed by gamma-subclass (17.1%), high G+C DNA
      (HGC) gram-positive (15.4%) and alpha-subclass (3.2%). Factory-II showed a
      similar pattern (32.7%, 31.8%, 17.5%, 16.4%, 1.6%) but with lower concentrations,
      while Factory-III showed predominant alpha- and beta-subclasses (25.2%, 25.0%)
      and CF cluster (24.8%) followed by the gamma-subclass (13.6%) and the HGC (11.4%)
      at much lower concentrations. The floc characteristic for factory-I and -II was
      normal, however factory-III had diffuse and atypical flocs. In conclusion, the
      FISH technique provided comprehensive information on the bacterial consortia of
      activated sludge samples. The compositions of the bacterial community and their
      concentrations together with the floc characteristics might be some of the
      reasons that affect the operational efficiencies among the 3 textile factories.

PMID- 16457177
TI  - Kinetic studies on the CuO/gamma-Al2O3 sorbent regeneration by methane-
      topochemical approach.
AB  - CuO impregnated gamma-Al2O3 support provides convenient adsorption and
      regeneration characteristics. These features give the potential to regard this
      chemisorption process as more effective, feasible and widely accepted than lime
      and limestone scrubbing in the removal of SO2 from the outlet gases.
      Thermogravimetric tests on the regeneration of the CuO/gamma-Al2O3 exhausted
      sorbent (first stage of the regeneration, CuSO4-->Cu0) with methane were
      conducted. Commercially available 1/8" gamma-Al2O3 spheres, loaded with 5.8 wt %
      of Cu were investigated. The tests concerning the isothermal regeneration
      kinetics were performed at temperatures: T = 700, 727 and 750 K, while a 20 cm3
      min(-1) flow of pure methane was used. To select the mechanism of the
      regeneration reaction, as well as to evaluate their kinetic parameters of the
      rate equations, the TGA data were compared with the series of theoretical
      topochemical kinetic models as advocated by Gardner, Hancock and Sharp's
      approach. The kinetic mechanism of the regeneration reaction in the initial stage
      of the process may be originally interpreted as the combination of both boundary
      surface-controlled reaction (contracting sphere) and the first-order kinetics
      models. Various diffusion limited kinetic equations have proved useful for the
      description of the final stage of the process. Both proposed models (two kinetic
      and four diffusion ones) fit fairly well to the experimental data (in their
      limited validity ranges) obtained in all three temperature values studied.

PMID- 16457179
TI  - Bioremediation of coal contaminated soil under sulfate-reducing condition.
AB  - The objective of this study was to investigate the biodegradation of coal-derived
      hydrocarbons, especially high molecular weight (HMW) components, under anaerobic
      conditions. For this purpose biodegradation experiments were performed, using
      specifically designed soil column bioreactors. For the experiment, coal
      contaminated soil was prepared, which contains high molecular weight hydrocarbons
      at high concentration (approx. 55.5 mgC g-drysoil(-1)). The experiment was
      carried out in two different conditions: sulfate reducing (SR) condition (SO4(2-)
      = 10 mmol l(-1) in the liquid medium) and control condition (SO4(2-)<0.5 mmol l(
      1)). Although no degradation was observed under the control condition, the resin
      fraction decreased to half (from 6,541 to 3,386 mgC g-soil(-1)) under SR
      condition, with the concomitant increase of two PAHs (phenanthrene and
      fluoranthene, 9 and 2.5 times, respectively). From these results, we could
      conclude that high molecular hydrocarbons were biodegradable and transformed to
      low molecular weight PAHs under the sulfate-reducing condition. Since these PAHs
      are known to be biologically degraded under aerobic condition, a serial
      combination of anaerobic (sulfate reducing) and then aerobic bioremediations
      could be effective and useful for the soil pollution by petroleum and/or coal
      derived hydrocarbons.

PMID- 16457178
TI  - An evaluation of variables affecting the stability and performance of down-flow
      anaerobic fixed bed reactors treating piggery wastewater.
AB  - The influence of the most important variables on the stability and performance of
      down-flow anaerobic fixed bed reactors treating piggery wastewater after primary
      sedimentation was evaluated at HRT in the range of 1-6 d and influent substrate
      concentration in the range of 2 to 12 g TCOD l(-1). The effect of HRT was more
      pronounced compared to that of influent strength. An increase in the HRT
      increased the process stability and process performance at different influent
      strengths. TCOD, SCOD, BOD5 TSS, organic nitrogen (N) and Orthophosphate (P)
      removals increased with the HRT, independently of the initial substrate
      concentration (S0). The increase in S0 brought about an increase in the attached
      biomass concentration (X) at the end of the experiment. Two empirical models
      based on the individual effect of HRT, X and S0 were evaluated and found to be
      adequate to describe the influence of these variables on the process performance.
      The first model took all the above-mentioned variables into consideration while
      the second model was simplified and based on the use of HRT as the only
      independent variable. The results obtained by using both models were found to be
      similar. This demonstrated that independently of the characteristics of the
      operation, the behaviour and performance of the reactors were comparable. The
      methane yield coefficient was found to be 0.3371 methane g(-1) TCOD removed.

PMID- 16457180
TI  - Estimation of (C/N) ratio for microbial denitrification.
AB  - Elemental balances of microbial growth have been applied to calculate (C/N) ratio
      in a denitrification process. The correlation between biomass yield coefficient
      and degree of reduction has been used to estimate the critical (C/N) ratio. It
      has been shown that when the degree of reduction of the substrate is lower than
      4.67, the critical value of (COD/N) is almost constant and equals 7.6 g O2 g(-1)
      N. The batch cultures of denitrifying bacteria Ervinia sp. on glucose, sodium
      acetate and methanol have been used to verify theoretical relations. The results
      of experiments generally agree with theoretical considerations.

PMID- 16457181
TI  - Association constants of Pb2+ with binding sites of fungal biomass using metal
      based titrations.
AB  - Biosorption is perceived as an alternative method for toxic heavy metal
      removal/recovery from aqueous effluents. This work focused on derivation of some
      key quantitative physico-chemical characteristics of a representative biosorbent
      material required for its further effective exploitation. The newly developed
      acid-base and metal-based titrator allowed the characterization of the
      chemisorption active sites of Rhizopus arrhizus biomass and the study of their
      metal affinity. This experimental approach, combined with an analytical method
      consisting of transforming the initial data enabled the calculation of the number
      and capacity of the reactive sites (Qads) and the metal affinity constants (Km)
      for lead sorption by R. arrhizus biomass. The pKm values for Rhizopus biomass
      varied between -3 and -6 for sites releasing no protons, -1 and 1 for sites
      releasing one proton, and > 8 for sites releasing two protons - combined with the
      Pb precipitation phenomenon. At low temperatures, the active binding site number
      was lower at lower lead concentrations whereas the precipitation was promoted at
      higher lead concentration values. Lead adsorption contributed modestly (11%) to
      its overall uptake and occurred at low lead concentrations onto strong and medium
      affinity binding sites. Micro-precipitation quickly commenced around active
      binding sites distinguished by their weak affinity whenever the solution lead
      concentrations reached 10(-6) or 10(-5) M and represented more than 85% of the
      total sorbed metal quantity. The work also demonstrated the usefulnes of the
      methodology reported here for characterizing complex biosorbent materials.

PMID- 16457182
TI  - [More research to the Health Care Centers].

PMID- 16457183
TI  - [Has sexual abuse of children increased?].

PMID- 16457184
TI  - [Nutrigenomics-key for identification of molecular effects of nutritional
      factors].

PMID- 16457185
TI  - [Musculoskeletal pain].

PMID- 16457186
TI  - [Neurologic disorders and driving performance].

PMID- 16457188
TI  - [Health factors of breast feeding in developed countries].

PMID- 16457187
TI  - [Magnetic resonance imaging of small bowel].

PMID- 16457189
TI  - [Adenoviruses in cancer therapy].

PMID- 16457190
TI  - [Merkel cell carcinoma in elderly].

PMID- 16457191
TI  - [What should a doctor do when suspecting child abuse?].

PMID- 16457192
TI  - [Weakened glucose balance and numb hands].

PMID- 16457193
TI  - [Just for fashion].

PMID- 16457194
TI  - [Adult cataract].

PMID- 16457195
TI  - [Chronological analysis of individually linked data for patients with intractable
      disease receiving public financial aid for treatment].
AB  - PURPOSE: Nationwide surveys of intractable disease patients receiving public
      financial aid for treatment were performed by Research Committee for Epidemiology
      of Intractable Disease (Ministry of Health and Welfare, Japan) 4 times in the
      past, in 1984, 1988, 1992 and 1997. The purpose of the present study was to
      clarify the features of continuance with intractable disease patients receiving
      public financial aid for treatment. METHODS: Individual information collected by
      each nationwide survey was linked using the disease, the residence, the sex, and
      the birth date. The proportion of intractable disease patients according to
      receipt duration, kind of medical insurance, sex and age was calculated with
      reference to the disease and an estimation of the receipt persistence rate was
      calculated for every year. Moreover, in consideration of variation in the data,
      average receipt persistence rates over years were also calculated. RESULTS:
      According to observation on individual patient's follow up, the proportion for
      which financial aid was discontinued within four years was 25%, while 70%
      continued receiving aid for at least four years and some 55% for eight or nine
      years. The proportion of those who continue receiving support long-term is high
      about the so-called autoimmune diseases, such as systemic lupus erythematosus,
      Behcet's disease, and the aortic syndrome. In contrast, with diseases having a
      poor prognosis, such as fulminant hepatitis, amyloidosis, and amyotrophic lateral
      sclerosis, periods of continuance are short. The proportion needing long-term
      continuation is higher in women than in men, especially with diseases which have
      long been eligible for support. However, with diseases for which receipt was
      started recently, there is a tendency for persistence to be higher in men than in
      women. CONCLUSION: With reform of insurance systems, including the medical system
      for intractable diseases, it is predicted that receipt continuation will change
      with alteration of social factors, and it is necessary to monitor receipt
      continuation carefully from now on.

PMID- 16457196
TI  - [Indoor air pollution due to 2-ethyl-1-hexanol airborne concentrations, emission
      sources and subjective symptoms in classroom users].
AB  - OBJECTIVE: 2-Ethyl-1-hexanol (2E1H) is a volatile organic compound (VOC) which
      seldom attracts attention in Japan. This study aimed at clarifying changes in its
      concentration over time, emission sources, and students' symptoms in classrooms
      of a university building where indoor air was found to be markedly polluted with
      2E1H. METHODS: From March 2001 through September 2002, we measured VOC
      concentrations in Building A, constructed in 1998, as well as Building B (Sept.
      2002), constructed over 30 years ago and considered as a control. Airborne
      concentrations of 13 carbonyl compounds were quantified with diffusive samplers
      and high-performance liquid chromatography, and those of 41 other VOCs with an
      active sampling method using charcoal tubes and a gas chromatograph with a mass
      spectrometer (GC-MS). In August 2002, we also measured VOC emissions from the
      floors using double-cylinder chambers and the airborne concentrations of
      phthalate esters by filtration sampling, both by GC-MS. Subjective symptoms in
      315 student classroom users in Building A and 275 in Building B were surveyed in
      July 2002 with anonymous self-administered questionnaires. RESULTS: 2E1H
      concentrations in Building A, which exceeded the Japanese recommended threshold
      of total VOCs (400 microg/m3) in some measurements, tended to be lower in winter
      and higher in summer, and did not show any tendency for decrease over time. No
      association was found between indoor concentrations of phthalate esters and those
      of 2E1H. The concentrations clearly differed between rooms, related to emission
      rates from the floors. Carpeting materials had been placed directly on the
      concrete floors in rooms with higher emission levels, whereas the carpeting
      materials and the concrete floor did not make contact in the room where emission
      was lower. The odds ratio for subjective symptoms with students in classrooms in
      Building A was not higher than in Building B where the 2E1H concentrations were
      low. However, a few students limited to Building A did complain of problems with
      the nasal passages, throat and lower airways. CONCLUSION: Compounds containing 2
      ethyl-1-hexyl moiety are presumably hydrolyzed to emit 2E1H when the backing of
      carpeting material is in contact with concrete floors. Although no significant
      difference was observed in symptoms between the student groups in the two
      buildings, this was possibly due to the small sample size. Measures to prevent
      2E1H emission and dose-response relationships in sensitive individuals should be
      studied further.

PMID- 16457198
TI  - [Variation in yield of needle scars with multipuncture BCG vaccination].
AB  - PURPOSE: BCG vaccination using the multipuncture percutaneous method has long
      been employed in Japan. The purpose of this study is to clarify whether the
      number of needle scars achieved the BCG vaccination differs with the vaccinating
      physician. METHODS: A total of 218 babies who were vaccinated at the age of 4
      months by different physicians at the Public Health Centres of Katsushika-Ward,
      Tokyo, were examined at the age of 3 years, in the three-year-old health check-up
      programme. The BCG vaccination with the multipuncture method generates 18 needle
      scars at a maximum. We examined each child for how many needle scars after BCG
      vaccination were visible, with reference to the vaccinating physician. RESULTS:
      The mean number of the visible scars was 9.23 (SD 6.11), and significantly
      smaller (P < 0.01) than that for all 22 Wards (12.18 +/- 5.64) investigated with
      the same method. The mean number of needle scars of the babies in Katsushika Ward
      was the third smallest among the 22 Wards and significantly smaller (P < 0.05)
      than the national average as determined in the nationwide survey conducted in
      2000. Significant differences were evident among the 7 physicians performing the
      vaccination, the best and second best means being 15.26 (SD3.62) and 14.59
      (SD3.58) respectively, and significantly larger (P < 0.01) than the means for the
      7 physicians. The worst mean was 3.43 (SD4.46), significantly smaller (P < 0.01)
      than the mean for the 7 physicians. CONCLUSION: The mean number of needle scars
      after BCG vaccination of babies significantly differed with the 7 physicians in
      the present study. Poor technique was presumed responsible for small numbers of
      scars and technical training is therefore necessary in order to improve the BCG
      vaccination outcome.

PMID- 16457197
TI  - [Development of a tool for assessment of local government health policy].
AB  - OBJECTIVE: A tool was developed for assessment of health status in communities to
      help formulate health policy of local governments and allow estimates of
      magnitude of changes in mortality with modification of selected risk variables.
      MATERIALS AND METHODS: A total of 25,201 men and 51,776 women aged 40-69 years
      who underwent health checkups in Ibaraki-ken, Japan, in 1993 were followed
      through 2002. Risk ratios for all cause, cardiovascular disease, cerebrovascular
      disease, ischemic heart disease, all cancer, and lung cancer deaths were
      calculated according to smoking, heavy alcohol consumption, obesity,
      hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol, and
      diabetes using a Cox proportional hazards model. Regression coefficients for body
      mass index, systolic blood pressure, serum total cholesterol, serum high-density
      lipoprotein cholesterol, and plasma glucose were also calculated by the model
      with quadratic terms. On the basis of the results, we developed a tool using
      Microsoft EXCEL, allowing estimation of the magnitude of changes in death rates
      according to variation in mean and standard deviation values for risk factors by
      impact fraction. RESULTS: The developed tool facilitates estimation of magnitude
      of changes in death rates with alteration in exposure rates and means/standard
      deviations of risk variables with intervention. The best magnitude of decline for
      all cause mortality with a 50% reduction of exposure to smoking was 10% in men.
      The magnitudes of decline in cardiovascular disease mortality with a 50%
      reduction in hypertension were 12% in men and 11% in women. Furthermore, the
      magnitude of decline in cardiovascular disease mortality if a 10% lowering of
      mean systolic blood pressure were achieved would be 22% in men and 18% in women.
      CONCLUSIONS: Our developed tool may be useful to assess health status in
      communities with cooperation between municipal and prefectural governments.

PMID- 16457199
TI  - [Correlates to male participation in disability prevention programs for the
      elderly].

PMID- 16457200
TI  - [Role of phagocytosis in infectious disease: overview].

PMID- 16457201
TI  - [Phagocytosis and killing of microorganisms].

PMID- 16457202
TI  - [Bacterial strategies for escaping the bactericidal mechanisms by macrophage].

PMID- 16457203
TI  - [Autophagic host defense mechanism].

PMID- 16457204
TI  - [Mechanism and risk for recognition of protozoan parasites in phagocytotic
      process].

PMID- 16457205
TI  - [Phagocytic clearance of virus infected cells and it's pathophysiological mean].

PMID- 16457206
TI  - [Stomatal patterning and differentiation: emerging role of cell-cell signaling].

PMID- 16457207
TI  - [Open, set, and close: DNA clamp loading mechanism revealed by electron
      microscopy].

PMID- 16457209
TI  - [Chimpanzee genome sequencing and comparative analysis with the human genome].

PMID- 16457208
TI  - [Mechanism of telomere replication and its relevance to the DNA double-strand
      break repair].

PMID- 16457210
TI  - [Descriptive epidemiology of pancreatic cancer].

PMID- 16457212
TI  - [Risk factor for pancreatic cancer--alcoholic abuse].

PMID- 16457211
TI  - [Smoking as a risk factor for pancreatic cancer].

PMID- 16457213
TI  - [Relation between diabetes mellitus and pancreatic cancer].

PMID- 16457214
TI  - [Chronic pancreatitis as a risk factor for pancreatic cancer].

PMID- 16457215
TI  - [Mechanistic insights for pancreatic carcinogenesis].

PMID- 16457216
TI  - [Molecular mechanism in pancreatic carcinogenesis: Ras gene].

PMID- 16457217
TI  - [Molecular mechanism in pathogenesis of pancreatic cancers: P53 oncosuppressive
      gene].

PMID- 16457218
TI  - [Molecular mechanism in pathogenesis of pancreatic neoplasms: p-Akt, PTEN].

PMID- 16457219
TI  - [Molecular mechanism in pathogenesis in pancreatic neoplasms: NF-kappaB].

PMID- 16457220
TI  - [Clinical characteristics of invasive ductal carcinomas of the pancreas according
      to the histological differentiation].

PMID- 16457221
TI  - [Intraductal papillary-mucinous neoplasm of the pancreas].

PMID- 16457223
TI  - [Mucinous cystic neoplasm of the pancreas].

PMID- 16457222
TI  - [Serous cystic tumor of the pancreas].

PMID- 16457224
TI  - [Treatment strategy for enteropancreatic neuroendocrine tumor].

PMID- 16457225
TI  - [JPS 5th ed. Classification of pancreatic cancer and JPS classification versus
      UICC classification].

PMID- 16457226
TI  - [Standard operation for pancreatic cancer according to Classification of
      Pancreatic Cancer (5th ed) by Japan Pancreas Society].

PMID- 16457227
TI  - [Classification of pancreatic cancer (Japan Pancreas Society) and lymph nodes
      dissection].

PMID- 16457228
TI  - [Extended radical resection for pancreatic head cancer].

PMID- 16457229
TI  - [Diagnosis of pancreatic cancer].

PMID- 16457230
TI  - [Advances of trans-abdominal ultrasonography and endoscopic ultrasonography in
      the diagnosis of pancreatic cancer].

PMID- 16457231
TI  - [Computed tomography for diagnosis of pancreatic cancer].

PMID- 16457232
TI  - [Magnetic resonance imaging for diagnosis of pancreatic neoplasm].

PMID- 16457233
TI  - [Latest advance in ERCP for the diagnosis and treatment of pancreatic cancer].

PMID- 16457234
TI  - [MRCP in the diagnosis of pancreatic carcinoma].

PMID- 16457235
TI  - [Percutaneous transhepatic cholangiography for diagnosis of pancreatic tumors].

PMID- 16457236
TI  - [Cytologic diagnosis of pancreatic cancer].

PMID- 16457237
TI  - [Diagnosis of pancreatic cancer from laboratory data].

PMID- 16457238
TI  - [Tumor markers for detecting pancreatic cancer].

PMID- 16457239
TI  - [Geneteic diagnosis for pancreatic tumors].

PMID- 16457240
TI  - [Early detection of pancreatic cancer].

PMID- 16457241
TI  - [PanIN classification system and precursors to pancreatic cancer].

PMID- 16457242
TI  - [Pancreatic carcinoma in the early stage and limited dilated lesions of the
      pancreatic ductuli].

PMID- 16457243
TI  - [Differential diagnosis between pancreatic carcinoma and chronic pancreatitis].

PMID- 16457244
TI  - [Management of pancreatic cancer: current therapy and continued development].

PMID- 16457245
TI  - [Japanese guidelines for treatment of pancreatic cancer based on evidence-based
      medicine].

PMID- 16457246
TI  - [Surgical treatment of pancreatic cancer].

PMID- 16457247
TI  - [Radiation therapy for locally advanced pancreatic cancer].

PMID- 16457248
TI  - [TS-1: S-1 based chemotherapy for far-advanced or relapsed pancreatic cancer].

PMID- 16457249
TI  - [Gemcitabine chemotherapy for patients with advanced or relapsed pancreatic
      cancer].

PMID- 16457250
TI  - [Irinotecan chemotherapy for patients with advanced or relapsed pancreatic
      neoplasm].

PMID- 16457251
TI  - [Activity of Taxanes for advanced and recurrent pancreatic cancer].

PMID- 16457252
TI  - [Combination chemotherapy in unresectable pancreatic carcinoma].

PMID- 16457253
TI  - [Adjuvant chemotherapy for pancreatic cancer].

PMID- 16457254
TI  - [IMRD therapy for patients with metastatic pancreas cancer].

PMID- 16457255
TI  - [Therapeutics with replication--selective virus (RSV) for pancreatic cancer].

PMID- 16457256
TI  - [Gene therapy of human pancreatic cancer cells by human interferon-beta gene].

PMID- 16457257
TI  - [Multimodal therapy for advanced pancreatic cancer].

PMID- 16457258
TI  - [Arterial infusion chemotherapy and radiotherapy after vascular supply
      distribution for pancreatic carcinoma].

PMID- 16457259
TI  - [Chemoradiotherapy including intraoperative radiotherapy for advanced and
      relapsed pancreatic tumors].

PMID- 16457261
TI  - [Preoperative chemoradiation for pancreatic cancer].

PMID- 16457260
TI  - [Concurrent chemoradiation therapy with gemcitabine for advanced or relapsed
      pancreatic tumors].

PMID- 16457262
TI  - [Chemoradiation therapy and immunotherapy for pancreatic cancer].

PMID- 16457263
TI  - [Drug distribution and alteration of blood flow for pancreatic arterial infusion
      chemotherapy].

PMID- 16457264
TI  - [Significance of thermo-chemotherapy for the patients with unresectable pancreas
      cancer].

PMID- 16457265
TI  - [Immunotherapy for pancreatic cancer by antibody directed against mucin].

PMID- 16457266
TI  - [Adoptive immunotherapy using MUC1--specific CTLs for unresectable pancreatic
      cancer].

PMID- 16457267
TI  - [Novel molecular-targeting peptide therapy for pancreatic cancer metastasis].

PMID- 16457268
TI  - [Staging and outcome of patients with pancreatic cancer].

PMID- 16457269
TI  - [Prognosis of pancreatic cancer from histopathological findings].

PMID- 16457270
TI  - [Prognostic significance of CA19-9 levels in patients with pancreatic cancer].

PMID- 16457271
TI  - [Assessment of the prognosis for pancreatic carcinoma by contrast-enhanced
      ultrasonography].

PMID- 16457272
TI  - [Quality of life in surgical treatment of pancreatic cancer].

PMID- 16457273
TI  - [Natural history of the malignant pancreatic tumor].

PMID- 16457274
TI  - [Post-operative digestive function and nutrition in pancreas cancer].

PMID- 16457275
TI  - [Trends & current status in cancer of the biliary tract].

PMID- 16457276
TI  - [Risk factors for biliary tract cancers: Nutritional factors].

PMID- 16457277
TI  - [Genetic susceptibility to gallbladder cancer in Japanese].

PMID- 16457278
TI  - [Risk factors for biliary tract cancers: Helicobacter species].

PMID- 16457279
TI  - [Why is gallbladder cancer more frequent in women than in men?].

PMID- 16457281
TI  - [Mechanism of biliary carcinogenesis in patients with pancreaticobiliary
      maljunction].

PMID- 16457280
TI  - [Stem cell and cancer in bile epithelial cells].

PMID- 16457282
TI  - [Genetic alterations in biliary tract carcinoma].

PMID- 16457283
TI  - [Mechanism of biliary carcinogenesis: Hepatotropic hepatis virus].

PMID- 16457284
TI  - [Modes of metastasis in gallbladder cancer].

PMID- 16457285
TI  - [Immunohistochemical analysis for cholangiocarcinoma].

PMID- 16457286
TI  - [Pathological studies on early cancer of the biliary tract].

PMID- 16457288
TI  - [General remarks on general rules for surgical and pathological studies on cancer
      of the biliary tract].

PMID- 16457287
TI  - [Histopathology of bile duct carcinoma and clinical symptoms].

PMID- 16457289
TI  - [Diagnosis of bile duct carcinoma].

PMID- 16457290
TI  - [US - IDUS - EUS for diagnosis of biliary tract neoplasms].

PMID- 16457291
TI  - [Role of MRI for diagnosis of biliary carcinoma].

PMID- 16457292
TI  - [Endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis of biliary
      tract neoplasms].

PMID- 16457293
TI  - [Magnetic resonance cholangiopancreatography (MRCP) for diagnosis of biliary
      tract neoplasms].

PMID- 16457294
TI  - [Percutaneous transhepatic cholangiography (PTC) for diagnosis of biliary tract
      neoplasms].

PMID- 16457295
TI  - [Diagnosis of biliary tract cancer by cytology].

PMID- 16457296
TI  - [Tumor markers in biliary tract cancer].

PMID- 16457297
TI  - [Genetic diagnosis of biliary tract cancer].

PMID- 16457298
TI  - [Management of diagnosis for biliary tract cancer].

PMID- 16457299
TI  - [Characteristics and management of cancer of the biliary tract in the elderly].

PMID- 16457300
TI  - [Staging score for biliary tract cancer].

PMID- 16457301
TI  - [High risk factors for bile duct cancer].

PMID- 16457302
TI  - [Role of ERCP in diagnosis of biliary carcinoma].

PMID- 16457303
TI  - [Occult pancreatobiliary reflux and gallbladder carcinoma].

PMID- 16457304
TI  - [Current status and perspective in surgical treatment of biliary cancer].

PMID- 16457305
TI  - [New approach to the treatment of biliary cancer].

PMID- 16457306
TI  - [Recent important insights in treatment of bile duct carcinoma].

PMID- 16457307
TI  - [Surgical treatment for intrahepatic cholangiocarcinoma].

PMID- 16457308
TI  - [Surgical treatment for hilar cholangiocarcinoma].

PMID- 16457309
TI  - [Surgical treatment for extrahepatic bile duct cancer].

PMID- 16457310
TI  - [Combined resection for hilar cholangiocarcinoma].

PMID- 16457311
TI  - [Diagnosis of invasion of tumor depth and surgical decision in gallbladder
      carcinoma].

PMID- 16457312
TI  - [Extent of the liver resection for gallbladder carcinoma based on the
      clinicopathological evidence].

PMID- 16457313
TI  - [Choice of operative procedures for carcinoma of the gallbladder on the basis of
      mode of hepatic invasion].

PMID- 16457314
TI  - [Laparoscopic approach for gallbladder cancer].

PMID- 16457315
TI  - [Lymph node dissection for gallbladder cancer].

PMID- 16457316
TI  - [Radiotherapy for carcinomas of the biliary tract].

PMID- 16457317
TI  - [Elementary guide for chemotherapy in gallbladder and biliary tree cancer].

PMID- 16457318
TI  - [Chemotherapy for biliary tract cancers: general remarks].

PMID- 16457319
TI  - [5 -fluoropyrimidines for treatment of biliary tract cancers].

PMID- 16457320
TI  - [Systemic chemotherapy with gemcitabine for advanced biliary tract carcinoma].

PMID- 16457321
TI  - [Adjuvant chemical treatment for bile duct cancer].

PMID- 16457322
TI  - [Thermo-chemo-radiotherapy for advanced biliary carcinoma].

PMID- 16457323
TI  - [Multimodal therapy for unresectable upper and hilar bile duct carcinoma].

PMID- 16457324
TI  - [Prognostic factors in the biliary tract cancer treatment].

PMID- 16457325
TI  - [Selection of therapy from the prognosis for stage IV hilar cholangiocarcinoma-
      extended hepatectomy vs stenting].

PMID- 16457326
TI  - [QOL of biliary tract cancer].

PMID- 16457327
TI  - [Palliative therapy in patients with biliary tract cancer].

PMID- 16457328
TI  - [Benign extrahepatic biliary stricture mimicking biliary carcinoma].

PMID- 16457329
TI  - [Usefulness of image workstation to diagnose cancer of the biliary tract].

PMID- 16457330
TI  - [Indication and significance of hepatopancreatoduodenectomy for gallbladder
      carcinoma].

PMID- 16457331
TI  - [Postoperative surveillance for patients with gallbladder cancer].

PMID- 16457332
TI  - [Extended hemihepatectomy after portal vein embolization for hilar bile duct
      cancer].

PMID- 16457333
TI  - [Pneumocystis jiroveci pneumonia as a complication of glucocorticoid therapy for
      interstitial pneumonia].
AB  - We evaluated the clinical features of pneumocystis jiroveci pneumonia (PCP) as a
      complication of glucocorticoid therapy for interstitial pneumonia We analyzed 74
      interstitial pneumonia patients receiving glucocorticoid therapy, of whom 7
      patients developed PCP. At the time of PCP diagnosis, the average duration of the
      glucocorticoid therapy was 71 days and the average daily dose of predonisolone
      was 37 mg. Circulating CD4+ lymphocyte counts were 370/microl on the average and
      more than 200/microl in three cases. PCP cases showed less circulating lymphocyte
      counts four weeks after the initiation of the therapy. Any cases receiving
      sulfamethoxazole-trimethoprim (TMP-SMX) did not develop PCP. In conclusion,
      interstitial pneumonia patients, who are treated with glucocorticoid, are benefit
      from TMP-SMX as PCP prophylaxis, but CD4 + lymphocyte counts greater than
      200/microl is no reason to denying PCP.

PMID- 16457334
TI  - [Community-acquired pneumonia with rhabdomyolysis].
AB  - We assessed the frequency and etiology of rhabdomyolysis in patients with
      community-acquired pneumonia. In 594 patients with community-acquired pneumonia
      whose serum CPK were measured, 25 patients (2.4%) were found to have
      rhabdomyolysis. Including 4 patients with mixed infections, the etiologies in 25
      patients with community-acquired pneumonia with rhabdomyolysis were as follows:
      Legionella species, 11 patients (44%); Influenza virus, 6 (24%); Streptococcus
      pneumoniae, 4 (16%); Chlamydia psittaci, 3 (12%); Mycoplasma pneumoniae, 2 (8%);
      unknown 3 patients (12%). The rates of rhabdomyolysis for each etiologic category
      were as follows: Legionella species, 26.8% (11/41); Chlamydia psittaci, 21.4%
      (3/14); Influenza virus, 9.5% (6/63) ; Streptococcus pneumoniae, 4.7%
      (4/85);Mycoplasma pneumoniae, 3.1% (2/65). Renal dysfunction with a serum
      creatinine concentration greater than 1.5 mg/dl occurred in 6 patients (24%). Our
      experience illustrates that 5 pathogens can cause rhabdomyolysis in patients with
      community-acquired pneumonia. Legionella species are the most common organisms
      followed by Influenza virus, Streptococcus pneumoniae, Chlamydia psittaci,
      Mycoplasma pneumoniae.

PMID- 16457335
TI  - [A case of brain metastasis discovered after surgery for lung cancer based on
      changes in CEA, in which long-term survival was obtained by repeated gammaknife
      irradiation].
AB  - A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June
      1998. Since a high level of tumor marker CEA persisted after surgery,
      chemotherapy was additionally performed, and the CEA level subsequently
      normalized. However, the CEA level increased in April 1999, and brain metastasis
      was found in the left occipital lobe, and the first gammaknife irradiation was
      performed. Multiple brain metastases were found when CEA increased again in
      August 1999, and the second gammaknife irradiation was performed. Moreover, brain
      metastases were found in the left frontal and occipital lobes in February 2000,
      and the third gammaknife irradiation was performed. CEA normalized thereafter,
      but increased in February 2001. Brain metastasis was found in the right occipital
      lobe, and the fourth gammaknife irradiation was performed. CEA has remained
      within the normal range for about 4 years thereafter. Long-term survival was
      possible by repeated gammaknife irradiation for brain metastases. Monitoring of
      CEA played an important role in finding recurrent brain metastasis in this
      patient.

PMID- 16457336
TI  - [Trichosporon antibodies (corrected of antigen) and HLA-antigen in summer-type
      hypersensitivity pneumonitis in a family].
AB  - We encountered a family in which all of the three members (the parents, a 45-year
      old woman and 51-year-old man, and their 15-year-old daughter) had Trichosporon
      cutaneum antibodies (corrected of antigen), and two (the parents) suffered from
      summer-type hypersensitivity pneumonitis in the late summer. The husband
      complained of dry cough, fever and dyspnea on exertion from July after severe
      interstitial pneumonitis and was treated with steroid pulse in September 2004.
      His wife visited our hospital and complained of a common cold-like symptom which
      progressed in August 2005. The couple were given diagnoses of summer-type
      hypersensitivity pneumonitis because they were positive for serum anti
      Trichosporon mucoides antigen and asahii antigen. Their asymptomatic daughter was
      positive for these antigens. Both wife and daughter had HLA-DQ 8 (3) and 9 (3)
      that are suggested to be important HLA antigens related to the occurrence of
      summer-type hypersensitivity pneumonitis.

PMID- 16457337
TI  - [A case of bronchial foreign body due to citrus fruit seed aspiration showing
      multiple pulmonary infiltration repeatedly].
AB  - We report a case of a bronchial foreign body in a 76-year-old citrus fruit
      farmer. The patient was detected patchy infiltration (ground-glass attenuation)
      of the right upper lung field on the chest X-ray on Dec. 26th, 2003. The shadow
      tended to disappear after treatment with antibiotics. The same shadow was
      detected again 10 months later and the patient underwent a bronchoscopic
      examination. A foreign body was found lodged in the center of the right upper
      bronchus, associated with bronchial stenosis due to mucosal edema. The abnormal
      shadow disappeared after the foreign body, which we decided was a citrus fruit
      seed, was removed. From the time course of the present illness and a
      retrospective evaluation of previous chest X-rays, the patient had aspirated the
      foreign body 18 months prior to his admission for bronchoscopy. We should be
      careful of the possibility of foreign bodies even when the elderly do not present
      a history of foreign body aspiration. It is important to consider the possibility
      of a bronchial foreign body in patients with repeated pneumonia, and to perform
      bronchoscopy aggressively.

PMID- 16457338
TI  - [Central diabetes insipidus caused by pituitary metastasis of lung cancer].
AB  - A 71-year-old man was admitted with high fever, thirst, polyposia and polyuria.
      After examination, lung cancer (adenocarcinoma T1NOM1, Stage IV) and central
      diabitus insipidus caused by pituitary metastasis of lung cancer, were diagnosed.
      We gave him desmopressin acetate, gamma knife surgery for pituitary metastasis
      and chemotherapy with paclitaxel and carboplatin, and his symptoms improved.
      However, his lung cancer progressed. Diabitus insipidus caused by lung cancer is
      rare.

PMID- 16457339
TI  - [A case of the multiple peripheral pulmonary artery branch stenosis].
AB  - A 31-year-old woman in whom primary pulmonary hypertension had been diagnosed at
      age 18, was admitted because of dyspnea on exertion and for evaluation of
      pregnancy risk. The perfusion scanning was not diagnostic, but chest CT suggested
      stenosis of pulmonary arteries instead of primary pulmonary hypertension.
      Echocardiograms and cardiac catheterization revealed pulmonary hypertension of
      pulmonary arterial pressure 71/13 (mean 39) mmHg with no cardiac defects.
      Selective pulmonary angiograms showed multiple stenosis of pulmonary arteries
      with poststenotic dilatations. We diagnosed multiple peripheral pulmonary artery
      branch stenosis with the pulmonary hypertension because systemic vasculitis was
      excluded because there were no signs of inflammation or any systemic arterial
      invlolvement This case was thought to be congenital, considering her history of
      over 30 years. In reports from western countries, maternal rubella and familial
      factors were important etiologic factors of this disease. Few cases have been
      reported in Japan and all cases, including the present case, were unrelated to
      the specific etiological factors. We recommended her to use birth control and
      have been observing her very carefully since the progression of the pulmonary
      hypertension is the major determinant of her prognosis.

PMID- 16457340
TI  - [A male case of acute sarcoidosis with fever, polyarthralgia, erythema nodosum,
      and bilateral hilar lymphadenopathy: Lofgren's syndrome].
AB  - A 27-year-old man initially had low back pain and ankle arthralgia. He was
      admitted because fever, cough, and polyarthralgia developed and continued for
      three months. Chest X-ray and CT revealed bilateral hilar and mediastinal
      lymphadenopathy with pulmonary lesions. Furthermore, elevated serum-ACE level and
      noncaseating epitheloid cell granuloma obtained by TBLB confirmed the diagnosis
      of sarcoidosis. After hospitalization, erythema nodosum appeared and ocular
      involvement was demonstrated. As a result, this case fulfilled the criteria of
      Lofgren's syndrome (arthritis, erythema nodosum, and BHL). Lofgren's syndrome is
      not uncommon in European countries, but is extremely rare in Japan. So far, only
      six cases with Lofgren's syndrome were reported in Japan, and all were female
      cases. This is the first male case in Japan. Lofgren's syndrome is usually a self
      limiting disease. We used steroids for this case and remission has been
      maintained after the beginning of the treatment for the past one year.

PMID- 16457341
TI  - [A case of sarcoidosis manifesting as acute febrile polyarthritis following
      bronchoalveolar lavage].
AB  - A 32-year-old man was incidentally found to have abnormal shadows on a chest X
      ray film and was admitted on May 2004. His chest images showed mediastinal and
      bilateral hilar lymphadenopathy. The serum level of angiotensin-converting enzyme
      was elevated. We also found non-caseating epithelioid cell granulomas in
      transbronchial lung biopsy specimens, and confirmed the diagnosis of sarcoidosis.
      We carried out bronchoalveolar lavage (BAL) for evaluation of disease activity of
      sarcoidosis. After BAL, he suffered high fever and polyarthralgia. Both ankles
      were extremely inflamed. We suspected infectious arthropathy caused by atypical
      pathogens and thus administered antibiotics, but they had no effect at all. Also,
      no findings suggesting collagen-vascular disorders, including rheumatoid
      arthritis, were detected. His symptoms improved after three-weeks of treatment
      with non-steroidal anti-inflammatory drugs. Thus, this case was diagnosed as
      having acute sarcoid polyarthritis. BAL may have influenced the onset of febrile
      arthritis in this patient This case indicates that sarcoidosis should be
      considered as a possible cause of acute febrile polyarthritis.

PMID- 16457342
TI  - [A case of Westermani Paragonimiasis with atypical change of CT findings].
AB  - A 47-year-old man presented with bloody sputum and a cavitary mass shadow was
      formed in his right middle lobe. Transbronchial lung biopsy revealed the presence
      of parasite eggs and eosinophil infiltration. Based on the positive reaction
      against Westermani Paragonimus by multiple dot ELISA, Westermani Paragonimiasis
      was diagnosed. The cavitary mass shadow disappeared after the treatment with
      Pragiquantel. This is a rare case of Westermani Paragonimiasis showing
      interesting changes of chest CT findings during its clinical course.

PMID- 16457343
TI  - Glass-fiber disks provide suitable medium to study polyol production and gene
      expression in Eurotium rubrum.
AB  - Eurotium species often dominate the fungal population in stored grain and are
      responsible for spoilage. In this study we tested the usefulness of glass fiber
      disks to aid the analysis of growth, polyol content and gene expression in E.
      rubrum in response to various water activities. Growth measurements based on
      ergosterol content and conidial production indicated that E. rubrum grew as well
      at 0.86 aw as 0.98 aw. The rate of growth was considerably reduced at 0.83 aw and
      0.78 aw. In contrast, under our conditions, Aspergillus flavus and A. nidulans
      were able to grow only in the highest water activity (0.98 aw). Mannitol was the
      predominant polyol in all three fungal species grown at 0.98 aw. When E. rubrum
      was grown at 0.86 aw or lower, glycerol comprised greater than 90% of the total
      polyols. After a shift from 0.86 aw to 0.98 aw, mannitol levels in E. rubrum
      increased to 89% of the total polyols within 24 h. Of six genes whose expression
      was measured by quantitative real-time PCR, three were affected by water
      activity. Expression of putative hydrophobin and mannitol dehydrogenase genes was
      higher at 0.98 aw than at 0.86 aw. A putative triacylglycerol lipase gene was
      expressed at higher levels in 0.86 aw.. The results of this study indicate that
      the disk method is suitable to study the effects of water activity on growth,
      polyol biosynthesis and gene expression in E. rubrum. The results also indicate
      the potential competitiveness of E. rubrum over A. flavus and A. nidulans in low
      water environments associated with stored grain.

PMID- 16457344
TI  - Species richness of tropical wood-inhabiting macrofungi provides support for
      species-energy theory.
AB  - A study was undertaken at the El Verde Field Station in Puerto Rico to determine
      the effect of energy available from newly dead trees on the species richness of
      macrofungal communities that inhabit them. It is hypothesized that there is a
      positive relationship between available energy and species richness. Energy was
      measured using the volume of the dead trees and the wood density of living trees
      of the same species. One hundred ninety-four logs of known tree species were
      surveyed 1 y for fruiting bodies of macrofungi at monthly intervals. For
      individual logs, log volume had a significant positive effect on macrofungal
      species richness. Younger logs had significantly higher species richness than
      older logs, and those with less apparent decay had more species than those with
      more decay. When logs were grouped by tree species, total wood volume and density
      of live wood had a significant positive effect and average log diameter had a
      negative effect on total species richness and abundance of the wood-inhabiting
      macrofungi. Macrofungal richness and abundance constantly increased with initial
      wood density; there was no evidence for a unimodal relationship. These results
      support the proposed relationship between species richness and energy.

PMID- 16457345
TI  - Spore dispersal of a resupinate ectomycorrhizal fungus, Tomentella sublilacina,
      via soil food webs.
AB  - Patterns of fungal spore dispersal affect gene flow, population structure and
      fungal community structure. Many Basidiomycota produce resupinate (crust-like)
      basidiocarps buried in the soil. Although spores are actively discharged, they
      often do not appear to be well positioned for aerial dispersal. We investigated
      the potential spore dispersal mechanisms of one exemplar of this growth form,
      Tomentella sublilacina. It is a widespread ectomycorrhizal fungus that sporulates
      in the soil organic horizon, can establish from the spore bank shortly after
      disturbance, but also can be a dominant species in mature forest stands. We
      investigated whether its spores could be dispersed via spore-based food webs. We
      examined external surfaces, gut contents and feces from arthropod fungivores
      (mites, springtails, millipedes, beetles, fly larvae) and arthropod and
      vertebrate predators (centipedes, salamanders) from on and around T. sublilacina
      sporocarps. Spore densities were high in the guts of many individuals from all
      fungivore groups. Centipede gut contents, centipede feces and salamander feces
      contained undigested invertebrate exoskeletons and many apparently intact spores.
      DAPI staining of spores from feces of fungivores indicated that 7-73% of spores
      contained intact nuclei, whereas spores from predators had lower percentages of
      intact nuclei. The spiny spores often were lodged on invertebrate exoskeletons.
      To test the viability of spores that had passed through invertebrate guts we used
      fecal droppings of the millipede Harpaphe haydeniana to successfully inoculate
      seedlings of Pinus muricata (Bishop pine). These results indicate the potential
      for T. sublilacina spore dispersal via invertebrates and their predators in soil
      food webs and might help to explain the widespread distribution of this species.
      It is likely that this is a general mechanism of dispersal for fungi producing
      resupinate sporocarps, indicating a need to develop a fuller understanding of the
      linkages of soil food webs and spore dispersal.

PMID- 16457346
TI  - Measurement of a rugulosin-producing endophyte in white spruce seedlings.
AB  - Previous studies conducted in growth chambers had demonstrated the successful
      experimental inoculation of white spruce seedlings with anti-insectan toxin
      producing needle endophytes. Needles colonized with the rugulosin-producing
      endophyte 5WS22E1 (DAOM 229536) contained rugulosin in concentrations that
      impaired spruce budworm growth. Here we report experimental inoculations
      conducted under nursery conditions. To improve the reliability of detecting
      successful colonization, a polyclonal assay was developed for the target
      endophyte 5WS22E1. It was able to reliably detect the fungus in 500 ng subsamples
      of colonized needles. Seventeen months post-inoculation, 330 seedlings from 1235
      inoculated were colonized. A random selection of 113 colonized seedlings was
      analyzed for rugulosin. Needles of most (90%) contained detectable concentrations
      of rugulosin. The range and distribution of the rugulosin concentrations was
      similar to that found in earlier tests done in growth chambers.

PMID- 16457347
TI  - Haploid vegetative mycelia of Armillaria gallica show among-cell-line variation
      for growth and phenotypic plasticity.
AB  - Vegetative mycelial cells of Armillaria are expected to have diploid nuclei.
      Cells from a single mycelium therefore would not be expected to differ from one
      another for ecologically relevant quantitative traits. We isolated two sets of
      basidiome cell lines (from spores and stipe cells) and one set of vegetative cell
      lines (from an attached rhizomorph) from a single contiguous Armillaria gallica
      mycelium. We isolated a second set of vegetative cell lines from the soil 20 cm
      from the above basidiome-rhizomorph complex. In all four sets of cell lines in
      situ DAPI-DNA measurements showed cells are haploid and quantitative-trait
      analyses of cell lines grown at different water potentials revealed high levels
      of among-cell-line genetic variation for both growth and phenotypic plasticity.
      Haploidy and the existence of ecologically relevant genetic variation within
      vegetative individuals are unexpected and mean that a process similar to
      evolutionary adaptation could take place within the soma of a genetic individual.
      We believe this is a key to understanding how large A. gallica mycelia survive
      exposure to variation in ecological conditions during lives that potentially span
      several tree (host) generations.

PMID- 16457348
TI  - Clonality in the postfire root rot ascomycete Rhizina undulata.
AB  - The aim of the present work was to investigate the potential for territorial and
      dispersive clonality in natural populations of the postfire root rot ascomycete
      Rhizina undulata. Population studies based on vegetative compatibility tests were
      done with strains isolated from individual sporocarps at five burned sites in
      three different localities (separated by 20-40 km) in the Curronian Spit of
      western Lithuania. Among a total of 103 strains, the tests identified 14 distinct
      vegetative compatibility groups (VCGs) of R. undulata, 13 of which were
      represented by 2-48 strains and three were encountered at 2-4 different sites.
      Occurrence on spatially separated sites of the same VCG of the fungus indicated a
      presence of dispersive clonality in R. undulata populations. On a local scale
      clusters of vegetative compatible sporocarps usually occupied discrete
      territories, implying territorial clonality. The two largest VCGs covered areas
      up to 7 and 3 m across. The results show that both dispersive and territorial
      clones are characteristics of natural populations of the fungus.

PMID- 16457349
TI  - Heterothallic mating observed between Mexican isolates of Glomerella
      lindemuthiana.
AB  - Although several reports have described the occurrence of the teleomorphic state
      of Glomerella lindemuthiana (anamorph, Colletotrichum lindemuthianum), there has
      been a lack of continuity in this research. To identify G. lindemuthiana isolates
      capable of developing the teleomorphic state, 19 Mexican isolates were analyzed.
      Three types of response were observed: (i) negative, where only mycelial growth
      with or without acervuli was observed; (ii) potential, where in addition to the
      above, spherical perithecia-like structures were observed; (iii) positive, where
      perithecia containing asci and ascospores were observed. All strains were self
      sterile and only one combination of strains produced fertile perithecia. From
      this fertile combination 168 individual ascospore cultures were isolated,
      including five from a single ascus. Forty-four monoascospore cultures were
      characterized with AFLP, confirming that these individuals were progeny from a
      sexual cross between the original two G. lindemuthiana isolates and that sexual
      reproduction in G. lindemuthiana is heterothallic in nature. Analysis of the
      parental strains with degenerate PCR primers indicated that sequences homologous
      to the HMG box of the MAT1-2 idiomorph are present in both parental isolates.
      This supports previous observations in other Glomerella species where the
      standard ascomycete configuration of distinct idiomorphs at the MAT locus does
      not hold true. The significance of these results is discussed.

PMID- 16457350
TI  - A phylogenetic study of the genus Haligena (Halosphaeriales, Ascomycota).
AB  - The genus Haligena (Halosphaeriales, Ascomycota), with two accepted species, is
      encountered frequently in marine habitats, especially on wood in temperate
      regions. Phylogenetic analyses of Haligena elaterophora (type species) and H.
      salina were undertaken, with partial large subunit ribosomal DNA sequences, to
      determine their relationships with other closely related genera in the order. The
      genus was shown to be polyphyletic within the Halosphaeriales with the type
      species forming a basal clade to the order. Haligena salina constituted a sister
      clade with weak support of Neptunella longirostris in all analyses. Haligena
      elaterophora and H. salina differ significantly in the nature of their ascospore
      appendages: wider, more sticky and strap-like in H. elaterophora and spoon-shaped
      at the point of attachment; in H. salina they are longer and narrower, finely
      drawn out filaments. A new genus, Morakotiella, is introduced to accommodate H.
      salina.

PMID- 16457351
TI  - Evaluation of the monophyly of Fomitopsis using parsimony and MCMC methods.
AB  - To evaluate the monophyly of Fomitopsis and elucidate phylogenetic relationships
      of its members, partial nuclear large subunit (partial 28S) ribosomal RNA genes
      were sequenced from 10 species of Fomitopsis and 15 related species. Phylogenetic
      analyses indicated that Fomitopsis was phylogenetically heterogeneous and its
      members were divided into three subgroups. The constrained tree excluding F.
      palustris (the type species of Pilatoporus) from Fomitopsis core group was
      rejected, thus rejecting the taxonomic concept to segregate Pilatoporus from
      Fomitopsis. The monophyly of taxa belonging to F. rosea complex was rejected,
      thus rejecting the complex definition based on morphological similarities. The
      exclusion of Piptoporus betulinus (the type species of Piptoporus) from
      Fomitopsis core group was rejected and Piptoporus proved to be heterogeneous in
      both best MP and MAP trees. The monophyly of F. officinalis with Fomitopsis core
      group also was rejected. Fomitopsis officinalis was closely related to Antrodia
      xantha and formed an independent lineage from Fomitopsis core group at the basal
      position of brown rotting fungi comprising Antrodia, Daedalea, Fomitopsis,
      Piptoporus and Postia. The MAP tree topologyobtained from MCMC computation of
      Bayesian inference was similar to the one of the best MP tree based on the
      parsimony analysis but showed a higher likelihood score in the Kishino-Hasegawa
      test and reflected better evolutionary patterns for the phylogeny of Fomitopsis.

PMID- 16457353
TI  - Pisolithus indicus, a new species of ectomycorrhizal fungus associated with
      Dipterocarps [corrected] in India.
AB  - Pisolithus is cosmopolitan in both tropical and temperate regions and forms
      ectomycorrhizal associations with a wide range of woody plants. Pisolithus
      indicus, a new species associated with Vateria indica (Dipterocarpaceae) is
      reported in this study from a dipterocarp native forest in the Western Ghats in
      India, using both morphological and molecular tools. The length of ITS1 and ITS2
      regions of the present collection differed with other sequences of Pisolithus
      available in the databases. Phylogenetic analysis indicates that this species did
      not show significant homology with existing Pisolithus sequences reported
      previously and formed a separate branch linking with another Pisolithus isolate
      from dipterocarps. Molecular and morphological evidence showed that P. indicus is
      a new species associated with dipterocarps in India.

PMID- 16457352
TI  - Galerina Earle: A polyphyletic genus in the consortium of dark-spored agarics.
AB  - The basidiomycete genus Galerina Earle accommodates more than 300 small brown
      spored agarics worldwide, predominantly described from the Northern hemisphere.
      The delimitation of species and infrageneric units hitherto has been based on
      morphological and, to some extent, ecological characters. In this study we have
      analyzed nuclear ribosomal LSU and ITS sequences to reveal infrageneric phylogeny
      and the phylogenetic placement of Galerina among the dark-spored agarics.
      Sequences from 36 northern hemisphere Galerina species and 19 other dark-spored
      taxa were analyzed, some of them obtained from EMBL/GenBank. Our results,
      received from Bayesian and distance methods, strongly suggest that Galerina is a
      polyphyletic genus. The LSU analysis shows that Galerina is composed of three or
      four separate monophyletic main groups. In addition, a few species cluster
      together with other dark-spored agarics. The same groups are recognized in the
      ITS tree and they correspond roughly to previously recognized subgenera or
      sections in Galerina. With high support our LSU analysis suggests that Gymnopilus
      is a monophyletic genus and that Gymnopilus and one of the Galerina lineages
      ("mycenopsis") are sister groups. The analyses further indicate that the Galerina
      lineages, as well as the genus Gymnopilus, could be referred to a strongly
      emendated family Strophariaceae, which corresponds largely to the family as
      circumscribed by Kuhner (1980). Our results affirm that morphological characters
      often are highly homoplastic in the agarics. At the present stage formal
      taxonomic consequences or nomenclatural changes are not proposed.

PMID- 16457355
TI  - The captured launch of a ballistospore.
AB  - Ballistospore discharge is a feature of 30000 species of mushrooms, basidiomycete
      yeasts and pathogenic rusts and smuts. The biomechanics of discharge may involve
      an abrupt change in the center of mass associated with the coalescence of
      Buller's drop and the spore. However this process occurs so rapidly that the
      launch of the ballistospore has never been visualized. Here we report ultra high
      speed video recordings of the earliest events of spore dispersal using the yeast
      Itersonilia perplexans and the distantly related jelly fungus Auricularia
      auricula. Images taken at camera speeds of up to 100,000 frames/ s demonstrate
      that ballistospore discharge does involve the coalescence of Buller's drop and
      the spore. Recordings of I. perplexans demonstrate that although coalescence may
      result from the directed collapse of Buller's drop onto the spore, it also may
      involve the movement of the spore toward the drop. The release of surface tension
      at coalescence provides the energy and directional momentum to propel the drop
      and spore away from the fungus. Analyses show that ballistospores launch into the
      air at initial accelerations in excess of 10,000 g. There is no known analog of
      this micromechanical process in animals, plants or bacteria, but the recent
      development of a surface tension motor may mimic the fungal biology described
      here.

PMID- 16457354
TI  - Molecular phylogeny of Hypoxylon and closely related genera.
AB  - Phylogenetic relationships were inferred among several xylariaceous genera with
      Nodulisporium or nodulisporium-like anamorphs based on the analyses of beta
      tubulin and alpha-actin sequences. One hundred nine cultures and three specimens
      of 83 representatives of these four genera were included in the study.
      Biscogniauxia taxa formed a well supported clade that was basal to the other
      taxa, while taxa of Hypoxylon and Daldinia comprised a large monophyletic group
      that contained two subclades. The first subclade encompassed Hypoxylon sect.
      Annulata and is accepted here as the new genus Annulohypoxylon. The second
      subclade contained taxa of Hypoxylon sect. Hypoxylon and Daldinia. Hypoxylon is
      restricted to include only those taxa in sect. Hypoxylon. Thirty-three epithets
      are made in Annulohypoxylon. Hypoxylon cohaerens var. microsporum is raised to
      the species level and accepted as A. minutellum. Hypoxylon polyporoideum is
      recognized as distinct from H. crocopeplum. Hypoxylon placentiforme is accepted
      as Daldinia placentiformis.

PMID- 16457356
TI  - Mannosyltransferase is required for cell wall biosynthesis, morphology and
      control of asexual development in Neurospora crassa.
AB  - Two Neurospora mutants with a phenotype that includes a tight colonial growth
      pattern, an inability to form conidia and an inability to form protoperithecia
      have been isolated and characterized. The relevant mutations were mapped to the
      same locus on the sequenced Neurospora genome. The mutations responsible for the
      mutant phenotype then were identified by examining likely candidate genes from
      the mutant genomes at the mapped locus with PCR amplification and a sequencing
      assay. The results demonstrate that a map and sequence strategy is a feasible way
      to identify mutant genes in Neurospora. The gene responsible for the phenotype is
      a putative alpha-1,2-mannosyltransferase gene. The mutant cell wall has an
      altered composition demonstrating that the gene functions in cell wall
      biosynthesis. The results demonstrate that the mnt-1 gene is required for normal
      cell wall biosynthesis, morphology and for the regulation of asexual development.

PMID- 16457357
TI  - Morphogenesis in germinating Fusarium graminearum macroconidia.
AB  - Fusarium graminearum (teleomorph Gibberella zeae) is a significant pathogen of
      wheat and corn. F. graminearum forms multicellular macroconidia that play an
      important role in dissemination of the disease. The spatial pattern of
      morphogenesis in germinating macroconidia is described. Germ tubes preferentially
      emerge from the apical cells in a bipolar pattern that appears to be common to
      filamentous fungi. Chitin deposition occurs at two locations: the spore apices
      and cortical regions of macroconidial cells that subsequently produce a germ
      tube. The spatial pattern of morphogenesis requires the presence of functional
      microtubules, which may be responsible for the transport of key polarity factors
      to specific sites. These observations suggest that F. graminearum possesses a
      regulatory system that marks germ tube emergence sites. Perturbation of this
      system may represent an effective approach for inhibiting colonization of host
      plant surfaces.

PMID- 16457358
TI  - Phylogenetic analysis of Tilletia and allied genera in order Tilletiales
      (Ustilaginomycetes; Exobasidiomycetidae) based on large subunit nuclear rDNA
      sequences.
AB  - The order Tilletiales (Ustilaginomycetes, Basidiomycota) includes six genera
      (Conidiosporomyces, Erratomyces, Ingoldiomyces, Neovossia, Oberwinkleria and
      Tilletia) and approximately 150 species. All members of Tilletiales infect hosts
      in the grass family Poaceae with the exception of Erratomyces spp., which occur
      on hosts in the Fabaceae. Morphological features including teliospore
      ornamentation, number and nuclear condition of primary basidiospores and ability
      of primary basidiospores to conjugate and form an infective dikaryon were studied
      in conjunction with sequence analysis of the large subunit nuclear rDNA gene
      (nLSU). Analysis based on nLSU data shows that taxa infecting hosts in the grass
      subfamily Pooideae form one well supported lineage. This lineage comprises most
      of the reticulate-spored species that germinate to form a small number of rapidly
      conjugating basidiospores and includes the type species Tilletia tritici. Two
      tuberculate-spored species with a large number of nonconjugating basidiospores,
      T. indica and T. walkeri, and Ingoldiomyces hyalosporus are also included in this
      lineage. Most of the species included in the analysis with echinulate, verrucose
      or tuberculate teliospores that germinate to form a large number (>30) of
      nonconjugating basidiospores infect hosts in the subfamilies Panicoideae,
      Chloridoideae, Arundinoideae and Ehrhartoideae. This group of species is more
      diverse than the pooid-infecting taxa and in general do not form well supported
      clades corresponding to host subfamily. The results of this work suggest that
      morphological characters used to segregate Neovossia, Conidiosporomyces and
      Ingoldiomyces from Tilletia are not useful generic level characters and that all
      included species can be accommodated in the genus Tilletia.

PMID- 16457359
TI  - Survival, growth and pathogenicity of Gaeumannomyces graminis var. graminis with
      different methods of long-term storage.
AB  - The fungal plant pathogen Gaeumannomyces graminis var. graminis was preserved
      with 12 different storage methods. Five strains, each with unique morphological
      and pathological characteristics, were used for comparison of the methods. The
      storage treatments included potato-dextrose agar slants, with or without mineral
      oil, stored at either 4 C, 28 C or ambient temperature; colonized agar plugs
      placed in glycerol solution at either -75 C or -20 C; colonized agar plugs placed
      in sterile deionized water at either 4 C or ambient temperature; and mycelial
      growth on intact or precut pieces of filter paper, desiccated and stored at
      ambient temperature. Survival was evaluated at 6, 12, 24, 36, 48 and 120 mo. The
      three best treatments for survival were PDA slants, with or without mineral oil,
      and colonized agar plugs stored in water, all at ambient temperature. All five
      fungal strains were recovered from all four replicates at each sampling date for
      agar plugs stored in water at ambient temperature. The worst treatments were agar
      slants and agar plugs in water stored at 4 C and agar plugs stored in glycerol at
      -20 C. Morphological characteristics were not affected by storage treatments. In
      general, there were minimal or no effects on growth and pathogenicity for all
      strains for all storage treatments with survival. Colonized agar plugs stored in
      water at ambient temperature provides an economical storage method (materials and
      labor) that does not need an electrical power for long-term maintenance.

PMID- 16457360
TI  - New species of Septobasidium from southern Costa Rica and the southeastern United
      States.
AB  - New species are described in Septobasidium, a genus of urediniomycete parasites
      on scale insects. One new species, S. gomezii, is described from Costa Rica, and
      another, S. meredithiae, is described from Louisiana. S. gomezii is most similar
      to S. septobasidioides, but macroscopic and microscopic differences support it
      being a distinct species. S. meredithiae is similar to S. alni and S. castaneum
      but differs from these species in several macroscopic and microscopic characters,
      especially when the species are observed on the same host tree and insect
      species. Another species collected only once in Costa Rica is listed with
      observations but it is not formally described here. This Septobasidium species
      shares some key characteristics with S. ramorum but combines a dense, compact,
      nearly black thallus and pigmented probasidia-like structures with spindle-shaped
      haustoria. Implications for taxonomy, morphological evolution and host
      specificity in Septobasidium are discussed.

PMID- 16457361
TI  - Some Xylaria species on termite nests.
AB  - Xylaria arenicola, X. brasiliensis, X. escharoidea, X. furcata, X. nigripes, X.
      piperiformis and X. rhizomorpha represent ancient names of fungi known to inhabit
      abandoned termite nests. We attempt to redescribe them and to reduce the
      confusion among them. Xylaria tanganyikaensis and X. readeri, species that might
      be associated with termite nests, are described. We describe a new variety, X.
      furcata var. hirsuta, and discuss an unnamed fungus that probably represents a
      new species. Photographs and a key are presented to aid the identification of
      these taxa.

PMID- 16457362
TI  - Ascospore diversity of bryophilous Hypocreales and two new hepaticolous Nectria
      species.
AB  - Hypocreales represents one of the most successful orders of ascomycetes on mosses
      and hepatics, and more than 30 obligately bryophilous species belonging to seven
      genera of Bionectriaceae and Nectriaceae are known. These fungi have a remarkably
      wide range of ascospore types that differ in form, size and septation. Especially
      heterogeneous are the ascospores of the six hypocrealean parasites recorded on
      European populations of Frullania dilatata. Patterns of distribution of
      bryophilous Hypocreales on this host appear to follow the principles of island
      biogeography. Two new leaf-perforating species of Nectria with unusual ascospores
      are described. Nectria foertheri Dobbeler sp. nov. grows biotrophically on
      Porella sp. in Guatemala, and N. lagodes Dobbeler sp. nov. is a necrotroph on
      Frullania dilatata in Italy and Greece.

PMID- 16457363
TI  - The biology and taxonomy of rust fungi associated with the neotropical vine
      Mikania micrantha, a major invasive weed in Asia.
AB  - Three microcyclic rust species were collected during surveys of the perennial
      asteraceous vine Mikania micrantha (Eupatorieae: Asteraceae) throughout its
      native range in the Neotropics but were absent in its invasive range in Asia. The
      commonest species, Puccinia spegazzinii with brown telioid telia, occurred
      wherever M. micrantha was found in South and Central America including the
      Caribbean island of Trinidad. Dietelia portoricensis, with occasional vestigial
      spermogonia and grayish-white to pale yellow columnar aecioid telia, was
      collected only in Costa Rica; while D. mesoamericana sp. nov., apparently
      restricted to Mesoamerica, can be distinguished by its abundant, yellowish
      orange, fertile spermogonia, yellow to pale brown telial columns, larger
      teliospores, and 4-spored rather than 2-spored metabasidia. The fact that all
      three species share a fundamentally similar symptomatology suggests a common
      origin.

PMID- 16457364
TI  - [Occupational diseases in Poland, 2004].
AB  - BACKGROUND: Our annual analysis of the epidemiology of occupational diseases is
      intended to indicate morbidity categories characterized by the highest risk of
      developing pathologies associated with working conditions and to assay variations
      in the frequency of those pathologies, depending on occupational exposure,
      medical factors, social and economic circumstances, legal regulations, and
      ongoing transformation of the national economy. MATERIALS AND METHODS: This work
      is based on the data compiled from "Occupational Disease Reporting Forms"
      received by the Central Register of Occupational Diseases in 2004. The data
      comprised information on individual diseases, gender and age of patients, and
      duration of occupational exposure to harmful agents responsible for the
      development of specified pathologies. These data were further classified by
      sectors of the national economy and voivodships (provinces). The incidence was
      specified in terms of the number of cases per 100,000 paid employees and per
      100,000 employed persons. RESULTS: In Poland, the number of occupational diseases
      diagnosed in 2004 accounted for 3790 cases. The incidence rate was 41.0 cases per
      100,000 paid employees. The highest incidence rates were noted for: chronic
      disorders of the voice organ (9.5 per 100 thousand), pneumoconioses (8.1),
      contagious and parasitic diseases (5.8), permanent bilateral hearing loss (5.5)
      and skin diseases (2.0). As much as 72.4% of patients affected by occupational
      diseases, had been exposed to harmful agents for longer than 20 years. In the
      industrial sectors of the national economy, the highest incidence was noted among
      workers employed in the mining industry (328.9 cases per 100,000 paid employees),
      particularly in coal mining (380.1). The highest incidence rates were recorded in
      the Lubelskie (122.0 cases) and Silesian (85.6 cases per 1000 workers)
      voivodships. CONCLUSIONS: The incidence of occupational diseases in Poland
      continues to abate. The downwards trend is primarily due to a lower incidence of
      hearing loss and chronic diseases of the voice organ.

PMID- 16457365
TI  - [Health reasons for work disability among municipal transport drivers].
AB  - BACKGROUND: The health condition of public transport drivers is one of the
      factors playing a role in assuring safety of passengers taking use of this kind
      of transportation means. Therefore, the assessment of pathologies occurring in
      this occupational group is essential from the prevention point of view. Drivers
      employed in the municipal transport system are at particular risk. The aim of the
      study was to define health reasons of work disability among bus and tram drivers
      in general and to indicate pathologies responsible for disabilities in
      particular. MATERIALS AND METHODS: The study covered 940 drivers (including 788
      men and 152 women) employed in a municipal transportation enterprise during the
      years 1996-2000. Bus (30%) and tram (22%) drivers as well as transport service
      workers (48%), aged over 45 years, but under the retirement age, were eligible
      for the study. The analysis of temporary work disability during a five-year
      period was based on sickness absence, sickness absence rate and the average
      duration of sickness absence. RESULTS: The analysis revealed that diseases of the
      circulatory system form the major group of pathologies responsible for total
      sickness absence among bus drivers (43%), tram drivers (27%) and transport
      service workers (27%). These disease are also a leading cause of earlier
      retirement. They mostly include ischemic heart disease in bus drivers and
      hypertension in tram drivers. Cancers (pleura, kidney and eye) were responsible
      for 9% of sickness absence in the group of male tram drivers, whereas endocrine,
      nutritional and metabolic diseases and immunity disorders (diabetes, disorders of
      thyroid gland) in 16% of female tram drivers. Diseases of the musculoskeletal
      system were major causes of sickness absence among female tram drivers (24%),
      whereas malignant and benign neoplasms of breast and uterine myoma in 24% of
      female transport service workers. CONCLUSIONS: The results of the analysis are in
      agreement with the literature findings and provide explicit evidence that
      employment in the municipal transport system is the risk factor responsible for
      the development of serious diseases such as musculoskeletal disorders and
      neoplasms. Bearing this in mind, this occupational group (bus and tram drivers)
      should be covered by specially designed prevention programs to protect them
      against these pathologies, turning special attention to health promotion at and
      outside workplace.

PMID- 16457366
TI  - [Genotoxicity effect of chronic lead exposure assessed using the comet assay].
AB  - BACKGROUND: Lead, an important xenobiotic, is globally well distributed. The IARC
      has classified inorganic lead compounds as possibly carcinogenic to humans. The
      study was designed to assess genotoxic effects in workers occupationally exposed
      to Pb. MATERIALS AND METHODS: The study comprised 62 male workers with chronic
      exposure to lead and 22 matched non-exposed men. DNA damage was assessed by
      single cell gel electrophoresis (known as comet assay) using peripheral blood
      lymphocytes. The level of DNA damage was determined as the percentage of cells
      with comets. RESULTS: Mean blood Pb (PbB) concentrations in workers exposed to
      lead were significantly higher than in controls (422.6 +/- 181.2 microg/l vs.
      81.0 +/- 37.84 microg/; p< 0.01). The level and the grade of DNA damage were
      significantly higher in workers exposed to lead (total--12.55 +/- 7.93%; grade 1-
      9.05 +/- 5.78%; grade 3--1.05 +/- 1.28%; p < 0.05) than in controls (total--6.63
      +/- 3.05%; grade 1--5.68 +/- 2.32%; grade 3--0.35 +/- 1.04%; p < 0.05). The
      highest level and the degree of DNA damage were observed in workers with PbB over
      500 microg/l and the lowest in workers with PbB lower than 200 microg/l.
      CONCLUSIONS: Our results suggest that lead, particularly in people with chronic
      occupational Pb exposure and high PbB may induce DNA damage in peripheral
      lymphocytes detected by the comet assay, and thus should be regarded as a
      potential agent harmful to the human chromosome. The comet assay can be used to
      monitor and evaluate biological toxic effects in humans occupationally exposed to
      lead.

PMID- 16457367
TI  - [Influence of mercury vapors on lymphocytes in vivo and on their susceptibility
      to UV-C and X-rays, and repair efficiency in vitro].
AB  - BACKGROUND: The aim of the study was to compare the levels of DNA and cytogenetic
      damage in lymphocytes from donors occupationally exposed to mercury vapors and
      from matched controls as well as their cellular susceptibility to radiation and
      capabilities to repair DNA damage induced by UV-C or X-ray exposures in vitro.
      MATERIALS AND METHODS: To estimate cytogenetic damage, the analysis of sister
      chromatid exchange frequency (SCE) was used, and to detect DNA damage the
      alkaline version of single cell gel electrophoresis (SCGE) was applied. To
      analyze cellular susceptibility, lymphocytes were exposed to 6 J/m2 of UV-C or
      irradiated with 2 Gy of X-rays. After challenging exposures, cells were incubated
      for 2 h with or without the presence of cellular mitogen (phytohemagglutinin-
      PHA). RESULTS AND CONCLUSIONS: The study did not show statistically significant
      differences either between the groups, levels of DNA damage (measured as the
      percentage of cells with comets or comet tail moments), or sister chromatid
      exchanges. Neither were there significant differences in the levels of DNA damage
      (measured as tail moment and comet length) detected in UV-C exposed lymphocytes
      after 2 h incubation in the presence or in the absence of PHA stimulating cells
      and in the susceptibility to X-ray radiation of lymphocytes between the groups of
      non-exposed persons and those occupationally exposed to mercury vapors. In the
      group exposed to mercury vapors, however, statistically significantly higher
      levels of non-repaired DNA damage measured in X-ray irradiated lymphocytes after
      2 h of incubation, with or without the presence of mitogen were observed compared
      to controls. Significant differences were observed in all types of DNA damage
      measures (comet tail length, % of DNA, in the comet and comet tail moments). As a
      result, lymphocytes of donors exposed to mercury vapors showed a statistically
      lower repair efficiency of X-ray-induced DNA damage both in non-stimulated (70.0%
      for the exposed, 85.7% for the non-exposed) and stimulated (84.0% for the exposed
      and 90.4% for the non-exposed) lymphocytes. Cellular DNA repair efficiency
      decreased with increasing number of years of occupational exposure. Statistically
      significant DNA repair deficiency in the donors exposed to mercury vapors was
      also observed when the groups were stratified to smokers and non-smokers.

PMID- 16457368
TI  - [Coexistence of occupational exposure to lead and sleep apnea syndrome as a cause
      of hypertension and arrhythmias. A case report].
AB  - A case of a 54-year-old man occupationally exposed to lead with diagnosed
      obstructive sleep apnea, hypertension and implanted artificial pacemaker due to
      atrioventricular dissociation of the third degree and pauses in sinus rhythm is
      presented.

PMID- 16457369
TI  - [Hepatitis D virus superinfection--a rare cause of occupational disease].
AB  - The authors present a case of occupational HDV infection in a 38-year-old nurse,
      HBsAg carrier, injured by a needle contaminated with blood of a drug user
      infected with HIV, HBV and HCV. After 2 months she developed acute viral
      hepatitis. HBV, HCV, HIV, CMV, EBV and other non-viral liver diseases were
      excluded. Finally, based on the source of exposure with high probability of HDV
      infection, the patient's positive serological test for HDV, and the result of
      histological examination of the liver, the diagnosis of viral hepatitis type D
      was established. Our case report suggests the need to consider possible
      occupational HDV infection in certain circumstances as described above.

PMID- 16457370
TI  - [Occupational exposure to biological agents and the protection of exposed workers
      according to the new legal regulations].
AB  - Directive 2000/54/EC deals thoroughly with issues referring to the protection of
      workers from risks related to occupational exposure to biological agents in the
      European Union. The ordinance of the Minister of Health on harmful biological
      agents at work and the protection of exposed workers implements its content into
      Polish legislation. This paper reviews essential records of the ordinance:
      definition of biological agents; classification of biological agents into four
      risk groups according to their level of risk of infection; employers' obligations
      concerning the protection of workers exposed to biological agents. The results of
      Phare project supporting implementation of the directive in Poland regarding
      distribution of information on occupational exposure to biological agents among
      State Sanitary Inspection and occupational medicine service staff and employers
      are also presented.

PMID- 16457372
TI  - [Diabetes mellitus--a problem for occupational medicine physicians].
AB  - The authors present current data concerning occupational certification in
      diabetic patients. Diabetes is one of the most common chronic diseases in
      everyday occupational medicine practice. In diabetes type 1, the main problem
      faced by an occupational medicine physician is to certify the presence or absence
      of contraindications for jobs, which pose the risk of serious traumas resulting
      from possible disturbances of consciousness. Diabetes type 2 is more common in
      occupational medicine. Its latent onset and slow progression may delay the
      diagnosis and lead to numerous complications. In this article we discuss the
      problem of risk for diabetic workers connected with hypoglycemia and current
      diagnostic rules under the prevention scheme.

PMID- 16457371
TI  - [Cardiological rehabilitation--a chance of returning to work].
AB  - According to the definition of the World Health Organization (WHO)
      "rehabilitation is a comprehensive and coordinated application of medical,
      social, educational and occupational measures to adapt a sick person to new life
      and to assist in gaining the best possible physical fitness". With respect to
      patients with cardiovascular diseases, the significance of comprehensive
      cardiologic rehabilitation is particularly emphasized. Return to work is by some
      authors perceived as a marker of rehabilitation efficiency. At the 8th World
      Rehabilitation Congress held in Dublin in May 2004, Perk (Sweden) reviewed the
      literature addressing the issue of returning to work. Over the recent seventy
      years, 460 publications devoted to this topic have been published. They mainly
      focus on the proportion of persons who return to work after myocardial
      infarction, percutaneous angioplasty of coronary arteries or implantation of
      aortic-coronary stents as well as on factors contributing to this success. It has
      been revealed that rehabilitation is one of numerous factors. Interestingly,
      socioeconomic and psychological, but not medical, factors play the major role in
      assuring return to work. There are also other factors which play a role, such as
      age < 50 years, education, social support, physical efficiency, disease
      perception, work satisfaction, absence of clinical symptoms, depression, fear,
      relations between the management and employees, place of residence (rural or
      urban area), economic status, sense of disability, waiting time for surgical
      procedure (period shorter than 3 months increases the frequency of returning to
      work). The number of studies providing evidence that rehabilitation enhances a
      chance of returning to work is rather limited. The authors review the state-of
      the-art in this area based on the available literature.

PMID- 16457373
TI  - [The role of quality management in x-ray protection in cardiologic
      catheterization laboratory].
AB  - Nowadays, there is a growing interest in procedures based on x-ray radiation and
      their application in diagnostic and therapeutic procedures. It is associated with
      still increasing radiation doses absorbed by the laboratory staff as well as by
      the patients, especially in catheterization laboratories of invasive cardiology,
      where procedures on the heart and vessels are performed. Current regal
      regulations impose the need to apply in x-ray laboratories the quality management
      system in radiological protection. The authors present some problems faced at an
      early stage of introducing and adopting this system in the catheterization
      laboratory of intervention cardiology. The possibilities of laboratory
      certification are discussed in line with international norms of the International
      Standards Organization (ISO). Some concepts for the future that could enhance the
      efficacy of x-ray doses monitoring and certain actions aimed at decreasing those
      doses are also proposed.

PMID- 16457374
TI  - Generation of polluted waters from mining wastes in a uranium deposit.
AB  - Dump consisting of 9500 tons of rich-in-pyrite mining wastes located in the
      uranium deposit Curilo, Western Bulgaria, was, after rainfall, an intensive
      source of acid drainage waters. These waters had a pH in the range of about 1.7
      4.5 and contained radionuclides (uranium, radium), heavy metals (copper, zinc,
      cadmium, lead, nickel, cobalt, iron, and manganese), arsenic and sulphates in
      concentrations usually much higher than the relevant permissible levels for
      waters intended for use in the agriculture and/or industry. The generation of
      these polluted waters was studied under real field conditions for a period of
      about seven years during different climatic seasons. It was found that the dump
      was inhabited by a diverse microflora in which some acidophilic chemolithotrophic
      bacteria were the prevalent microorganisms. The solubilization of the above
      mentioned pollutants from the dump material was connected mainly with the
      oxidation of pyrite and other sulphide minerals by these bacteria. Their activity
      depended on some essential environmental factors such as temperature, pH, and
      water, oxygen and nutrient contents in the dump.

PMID- 16457375
TI  - Exposure to moulds in flats and the prevalence of allergic diseases--preliminary
      study.
AB  - The presented study concerned mycological analysis of buildings in Lodz and
      evaluation of the role between filamentous fungi contaminated flats and
      inhabitants health (allergic airway diseases). 49 inhabitants of 20 flats with
      signs of moulds contamination were examined. Air samples were collected in houses
      and outdoors. In all inhabitants skin prick tests (SPT) to common allergens and
      to standardized particular fungal extracts were performed. Moreover, total and
      serum specific IgE to moulds, rest spirometry were measured in all subjects.
      Level of moulds contamination in the air of flats was high and in 75% cases
      exceed accepted limits. The most frequent species isolated from examined rooms
      were: Penicillium, Cladosporium, Aspergillus, Acremoniu and Alternaria. The most
      frequent symptoms reported by examined subjects were rhinitis (N = 29, 59.2%),
      conjunctivitis (N = 29, 59.2%), chronic cough (N = 24, 49%), dyspnea (N = 15,
      30.6%) and skin symptoms (N = 24, 49%). Elevated IgE level was found in 12
      subjects (24.5%) and in three patients (6.1%) mould specific serum IgE were
      detected. Nineteen out of all subjects (38.8%) had positive SPT to common
      allergens (house dust mites, grass and tree pollens). Eight out of these patients
      (16.3% of the group) were sensitized to moulds (Candida albicans, Alternaria
      alternata, Botrytis cinerea, Trichophyton mentagrophytes, Helminthosporium
      halodes, Aspergillus). In all cases sensitisation to moulds was accompanied by
      allergy to other common allergens. No isolated hypersensitivity to moulds was
      found. Although the frequency of self-reported symptoms was high, the prevalence
      of atopy and allergic diseases seems to be similar to that found in general
      population, but that statement must be confirmed by comparison of the control
      group.

PMID- 16457376
TI  - Mycological analysis of cereal samples and screening of Fusarium strains' ability
      to form deoxynivalenole (DON) and zearalenone (ZEA) mycotoxins--a pilot study.
AB  - Filamentous fungi are cosmopolitan microorganisms found in almost all
      environments. It should be pointed out that occurance of moulds on food or feed
      may cause health disorders in humans and animals. Mycoflora appears as a source
      of toxic methabolites, mycotoxins, which hepatotoxic, genotoxic, nefrotoxic and
      carcinogenic abilities were already proven in several studies. Hense mycological
      analysis of cereal grains raises as an important manner in evaluation of food and
      feed health features. Among the most frequent cereal contaminants Alternaria,
      Aspergillus, Fusarium and Penicillium strains are mentioned. Due to their ability
      to grow on cereals during both its field growth and storage, Fusarium moulds
      occure to be an important contamination factors in food and feed industry. In
      this study Fusarium strains isolates from wheat and maize were examined in order
      to recognize their abilities to produce two toxins: zearalenon (ZEA) and
      deoxynivalenole (DON). Mycological analysis shown differentiation within fungal
      microflora occuring in samples of different storage conditions, where Fusarium
      strains represented aproximately 20-70% of all mould species present. In purpose
      of Fusarium strains species evaluation, isolates were mycologically analysed. In
      the second step of the project, toxicological screening of isolates was performed
      using Thin Liquid Chromatography (TLC) evaluating toxigenic potential of single
      strains' production of ZEA and DON. This data gives the possibility of pointing
      the most toxigenic strains and also shows differentiations in their occurance in
      cereals. This paper presents introductory research data, which can be useful in
      recognition of cereal contamination with moulds and their toxic methabolites.

PMID- 16457377
TI  - Microbiological quality of carbonated and non-carbonated mineral water stored at
      different temperatures.
AB  - The microbiological quality of five brands of carbonated and non-carbonated
      mineral water sold in Poland was studied. The study was carried out on the
      survival of heterotrophic bacteria at 22 and 37 degrees C (pour plate technique)
      in the samples of mineral waters stored at 4 and 22 degrees C. The one hundred
      ten bottles (twenty two bottles of each of the five brands) of carbonated and
      uncarbonated mineral waters with different levels of dissolved solids and organic
      content were chosen to microorganisms study. Ten bottles of mineral water were
      studied initially. Fifty bottles were stored at 4 degrees C, the other fifty were
      kept at 22 degrees C. The haemolysing bacteria in 1 cm3; E. coli, P. aeruginosa
      and A. hydrophila in 250 cm3 of mineral water were unidentifiable. Total viable
      count of heterotrophic bacteria at 22 and 37 degrees C in 1 cm3 of mineral water
      was the highest respectively for brand T and for brands T and M; the lowest for
      brand Z. Initially, approximately 29% of 110 water samples (respectively 4% of
      carbonated and 55% of uncarbonated) had bacterial counts greater than Ministry of
      Health's standards, notwithstanding the number of water samples which doesn't
      perform requirements grew up to 47% (respectively 36% of carbonated and 58% of
      uncarbonated) when the time of TVC 37 and 22 degrees C incubation was elongated
      from 1 and 3 days to 3 and 14 days respectively. The temperature of storage was
      inessential for the numbers of studied microorganisms. The most important factors
      were the brand, time of storage and the carbonating or non-carbonating of water.
      The highest numbers of the bacteria analysed were detected in non-carbonating
      water, irrespective of the water brand and temperature of storage.

PMID- 16457378
TI  - Survival of Escherichia coli and Aeromonas hydrophila in non-carbonated mineral
      water.
AB  - The study was carried out on the survival of Escherichia coli and Aeromonas
      hydrophila in samples of mineral waters. Enumeration of the bacteria was
      performed by spread inoculation of samples (0.1 cm3) over the surface of selected
      media in Petri plates. Twenty bottles (four bottles of each of the five brands)
      of non-carbonated mineral waters with different levels of dissolved solids and
      organic content were chosen to study every strain. Ten bottles were stored at 4
      degrees C, the other ten were kept at 22 degrees C. Half of the samples of
      mineral water was filtered, the remaining water was unfiltered. The resulting
      growth curves depended on the time of storage. The number of E. coli increased
      during the first two weeks (except the seventh day) and decreased during the next
      days. E. coli was detected in 70% of samples of water after 182 days. The number
      of A. hydrophila decreased during the first three days, increased on the seventh
      day and decreased during the next days. A. hydrophila was detected in 15% of the
      samples of water after 182 days. The temperature of storage was inessential for
      growth. The most important factors were the brand and the filtering or
      unfiltering of water. The highest numbers of the bacteria analysed were detected
      in filtered water, irrespective of the water brand and temperature of storage.

PMID- 16457379
TI  - Prevalence of anisakin nematodes in fish from Southern Baltic Sea.
AB  - Nematodes from the superfamily Ascaridoidea (families Anisakidae and
      Raphidascarididae) are worldwide distributed parasites. Their live cycles include
      many species of water invertebrates and teleostean fish as intermediate hosts,
      and fish, sea mammals or fish-eating birds being definitive hosts. Humans can be
      infected with some of these parasites after consumption of raw or wrongly
      processed fish. The parasitological investigations of fish (herring, cod and
      flatfish) from southern Baltic (ICES 24-26) provided in the years 80 and 90
      showed their infection with larvae of several anisakid species: Anisakis simplex
      s. str., Contracaecum osculatum C and Hysterothylacium auctum. Sporadically
      Pseudoterranova decipiens and Raphidascaris acus were also found. Larvae of
      Anisakis simplex were noted mainly in herrings, C. osculatum primarily in cods
      and H. auctum in flounders. Additionally, preserved herrings (marinated, smoked)
      were also investigated and sporadically live larvae of A. simplex were found. The
      main etiological agent of human anisakidosis worldwide is A. simplex. Although
      the live cycle of this nematode cannot be completed in the Baltic Sea--this
      nematode is brought to the Baltic by infected herring migrating from the North
      Sea for spawning in coastal waters of the Southern Baltic--the prevalence and
      intensity of infection with larvae of this nematode species were the highest in
      fish investigated by us. The results obtained suggest the possibility of the
      human infection with A. simplex larvae in Poland.

PMID- 16457380
TI  - The cytotoxic and genotoxic effects of conjugated trans-2-nonenal (T2N), an off
      flavor compound in beer and heat processed food arising from lipid oxidation.
AB  - This study investigates the toxic effect of E(2)nonenal (trans-2-nonenal, T2N)
      and its conjugate with horse muscle myoglobin (Mb) tested on murine cell line
      L929 and human cell line A549, as well as the genotoxic effect of these compounds
      assayed by measuring of micronuclei in human cells K562. It is an aldehyde, which
      is occurring as the substance responsible for an off flavour in aged beers, but
      originates also from lipid oxidation in heat processed food. T2N is an aldehyde
      formed from linoleic acid as a secondary oxidation product. The modification of
      Mb with T2N was analyzed with the use of SDS-polyacrylamide gel electrophoresis
      (SDS-PAGE), and electrospray ionization mass spectrometry (ESI-MS). Results from
      SDS-PAGE suggest that T2N substitutes Mb and additionally causes cross-linking
      with polymerization of Mb resulting in an insoluble fraction. The ESI-MS spectrum
      of the soluble fraction used in the toxicity tests, demonstrated that conjugation
      of T2N with Mb yielded Mb adducts with one residue of trans-2-nonenal per
      myoglobin molecule as the major fraction and adducts with different numbers of
      T2N molecules as minor fractions. In the cytotoxicity assay the T2N and its Mb
      conjugate causes 50% destruction of cells at the concentration 95-125 microg/ml
      and 200 microg/ml respectively, when L929 and A549 cell lines were used, whereas
      Mb control tested up to 2000 mg/ml was without any cytotoxic effect. In
      genotoxicity in vitro assay we have observed that the T2N and its Mb conjugate
      expressed the genotoxicity. The number of micronuclei in human K562 cells reached
      26 +/- 2.16 promille (MN/1000 cells), comparing to 62 +/- 8.64 MN/1000 cells for
      the reference free T2N, whereas a control value was 10.33 +/- 1.25 MN/1000 cells.
      The studied compounds expressed also the apoptotic effect in K562 cells as the
      number of apoptotic cells increased to 44.67 +/- 4.92 promille for T2N-Mb,
      comparing to 168.67 +/- 37.28 promille for free T2N, whereas a control value was
      30.33 +/- 1.36 promille for Mb. In these assays the T2N-Mb conjugate is several
      times more toxic in relation to control protein. Results indicate that T2N
      adducts with protein are potent to induce various cytotoxic and apoptotic effects
      when assayed in vitro tests. It suggests that higher level of such aldehyde might
      create in organism severe potential of toxicity.

PMID- 16457381
TI  - Mechanical transmission of pathogenic organisms: the role of cockroaches.
AB  - BACKGROUND & OBJECTIVES: Cockroaches (Diploptera punctata) are basically tropical
      insects and will do their best to find a home that is both warm and moist. Their
      involvement in the transmission of tropical diseases is poorly investigated in
      Africa. METHODS: A study on the bacterial, fungal and parasitic profile of
      cockroaches trapped in and around houses in Ekpoma was carried out using standard
      microbiological techniques. RESULTS: Of a total of 234 cockroaches trapped from
      different sites (toilets, parlours, kitchens and bedrooms) in houses with pit
      latrines and water system, the bacterial, fungal and parasitic isolates were
      identical irrespective of the site, these included: E. coli, Klebsiella
      pneumoniae, Proteus vulgaris, Proteus mirabilis, Citrobacter freundii,
      Enterobacter cloacae, Salmonella sp, Pseudomonas aeruginosa, Serretia marcescens,
      S. aureus, S. feacalis, S. epidermidis, Aeromonas sp, Candida sp, Rhizopus sp,
      Aspergillus sp, Mucor sp, cysts of E. hystolitica, oocysts of C. parvum, C.
      cayetenensis and Isospora belli, cysts of Balantidium coli, ova of Ascaris
      lumbricoides, Anchylostoma deodunalae, Enterobius vermicularis, ova Trichuris
      trichura, larva of Strongyloides stercoralis. Cockroaches trapped in the toilets
      of houses with pit latrines had a mean bacterial and parasites count of 12.3 x
      10(10) org/ml and 98 parasites/ml respectively, while those trapped in the houses
      with water system had a mean bacterial and parasitic count of 89.5 x 10(7) org/ml
      and 31 parasites/ml respectively. A bacterial count of 78.9 x 10(7) org/ml was
      recorded from cockroaches trapped from the kitchens of houses with pit latrines.
      On the other hand a mean bacterial and parasitic count of 23.7 x 10(6) org/ml and
      19 parasites/ml were recorded from kitchens of houses with water system.
      INTERPRETATION & CONCLUSION: Cockroaches represent an important reservoir for
      infectious pathogens, therefore, control of cockroaches will substantially
      minimise the spread of infectious diseases in our environment.

PMID- 16457382
TI  - Hydrolytic enzyme activity in rhesus monkey placenta during early gestational
      malaria: histochemical studies.
AB  - BACKGROUND & OBJECTIVES: Early gestational malaria is found to be more fatal than
      late gestational infection but the pathophysiology of early gestational placenta,
      the maternofoetal organ responsible for maintenance of pregnancy, remains
      unexplored. Present study dealing with hydrolytic enzymes in early gestational
      placenta of rhesus monkeys during Plasmodium cynomolgi infection was anticipated
      to provide a better insight into the functional impairment of this organ during
      early gestational maternal malaria. METHODS: Experimental monkeys (Macaca
      multtta) at 2-2 1/2 months of pregnancy were inoculated with P. cynomolgi
      bastianelli. After attaining first peak of parasitaemia the animals were
      anesthetised and placentae were collected for histochemical studies. The snap
      frozen, cryostat sections were subjected to histochemical reactions for acid
      phosphatase and alkaline phosphatase. RESULTS: The placental syncytiotrophoblast
      showed a loss in alkaline phosphatase activity, while the trophoblast layers and
      phagocytic cells of the maternal blood showed increased acid phosphatase activity
      during early gestational malarial infection. Morphological damage to the
      placental tissue whenever occurred was associated with altered Alk pase activity.
      INTERPRETATION & CONCLUSION: The altered distribution of Ac pase and Alk pase in
      malaria infected early gestational placenta has been discussed in the light of
      placental function. It could be concluded by present studies that these malaria
      induced changes in hydrolytic enzyme activities in monkey placenta have a direct
      bearing on functional and morphological integrity of the placental tissue. These
      changes are apparently responsible for early gestational foetal death and
      abortions as reported in literature.

PMID- 16457383
TI  - Study of social determinants of malaria in desert part of Rajasthan, India.
AB  - BACKGROUND & OBJECTIVES: A longitudinal study on social determinants of malaria
      has been undertaken in different villages of Ramgarh PHC of Jaisalmer district,
      Rajasthan. The study aims to determine social determinants of malaria as
      applicable to existing cast groups of desert part of Rajasthan. METHODS: Out of
      940 households in five villages, 150 households of Rajput community (forward
      community) and Meghwal community (backward community) were selected at random to
      study whether due to different behaviour of existing caste groups, transmission
      of malaria and its intensity also vary or not. RESULTS: It was found that
      magnitude of malaria was three times more in the Meghwal community as compared to
      Rajput community. In-migration of natives importing malaria was found to be
      prominent cause of more malaria incidence in the backward community.
      INTERPRETATION & CONCLUSION: An intervention policy aiming to study existing
      status of knowledge among different caste groups of desert areas could lead to a
      substantial control over in-migration as well as further transmission of disease
      in the desert part of Rajasthan.

PMID- 16457385
TI  - Malaria infection in HIV-seropositive and HIV-seronegative individuals in Jos
      Nigeria.

PMID- 16457384
TI  - In vitro evaluation of marketed antimalarial chloroquine phosphate tablets.
AB  - BACKGROUND & OBJECTIVES: The aim of the present study is to investigate the
      physicochemical equivalence of seven brands of tablets containing chloroquine
      phosphate, an antimalarial purchased from different retail pharmacy outlets.
      METHODS: The quality and physicochemical equivalence of seven different brands of
      chloroquine phosphate tablets were assessed. The assessment included the
      evaluation of uniformity of weight, friability, crushing strength, disintegration
      and dissolution tests as well as chemical assay of the tablets. RESULTS: All the
      seven brands of the tablets passed the British Pharmacopoeia (BP) standards for
      uniformity of weight, disintegration and crushing strength. One of seven brands
      failed the friability test. One of the brands did not comply with the standard
      assay of content of active ingredients. Dissolution test passes the
      pharmacopoeial standards for chloroquine phosphate tablets. There were no
      significant differences in the amounts of chloroquine phosphate released from the
      different brands. INTERPRETATION & CONCLUSION: Out of the seven brands of anti
      malarial chloroquine phosphate tablets only one brand fails to meet BP quality
      specifications which shows constant market monitoring of new products to
      ascertain their equivalency to pharmacopoeial standards.

PMID- 16457386
TI  - First report on the presence of morphospecies A and B of Phlebotomus argentipes
      sensu lato (Diptera: Psychodidae) in Sri Lanka--implications for leishmaniasis
      transmission.

PMID- 16457387
TI  - Comparative efficacy of Annona squamosa Linn. and Pongamia glabra Vent. to
      Azadirachta indica A. juss against mosquitoes.

PMID- 16457388
TI  - [Image of the month. Macronodular lesions of the lung].

PMID- 16457389
TI  - [Uterine carcinosarcoma in a teenager: report of a case macroscopically mimicking
      rhabdomyosarcoma].
AB  - Uterine carcinosarcoma (malignant mixed mullerian tumor) is uncommon. We report
      the case of a 17-year-old patient who complained of pelvic pain and abnormal
      genital bleeding, and had a voluminous hemorrhagic tumor protruding through the
      vaginal os. Hysterectomy was performed. The histopathologic and
      immunohistochemical evaluation led to the diagnosis of uterine carcinosarcoma.
      Adjuvant chemotherapy was given. In spite of the surgical treatment, the
      evolution was fatal with widespread metastases. From data of the literature, we
      discuss the diagnosis, histogenesis and treatment of this rare tumor.

PMID- 16457390
TI  - ["Fulminant" endocarditis due to Staphyloccocus aureus].
AB  - We report two cases of "fulminant" endocarditis due to Staphyloccoccus aureus. In
      both cases, the echocardiographic and bacteriologic diagnosis was esthablished in
      a clinical picture of severe sepsis and thrombocytopenia evolving after a fever
      of less than 3 days duration.

PMID- 16457391
TI  - [Integration of pharmacogenetics in the medical practice].
AB  - Today, the initiation of any medical treatment still raises questions about its
      efficacy and safety. Indeed, therapeutic responses vary over time and between
      individuals and are influenced by age, sex, other treatments and the pathology
      itself. Genetic factors are thought to be responsible for 20 to 95% of these
      individual variations. Recent advances in biotechnology, molecular genetics and
      genomics allow a better understanding of drug metabolism and action.
      Pharmacogenetics, compiling phenotypic and genotypic data, may lead to a more
      personalized treatment. To allow a better approach of pharmacogenetics and
      pharmacogenomics, we will define these two terms and describe their actual and
      future clinical application.

PMID- 16457392
TI  - [Vaccinations in HIV-infected children].
AB  - The increased vulnerability of HIV infected children to infections supports the
      principle of vaccination. This article summarizes the available data on the
      practice of vaccination among HIV infected children. Vaccination is, in general,
      harmless and efficacious in those children. The World Health Organisation (WHO)
      guidelines are very similar to other recommandations. Nevertheless, the HIV
      related immunosuppression reduces the vaccination benefits. Moreover, serious
      complications are possible after BCG-vaccine administration in seriously
      immunocompromised children. Therefore, children with AIDS should not be given
      this vaccine. The benefits of anti-poliomyelitis and anti-measles vaccination
      markedly exceed the low post-vaccination risk reported among these children.

PMID- 16457393
TI  - [Depression and coronary artery disease].
AB  - Depression and cardiovascular diseases represent a major public health problem
      worldwide. Recent studies have shown that depression is a risk factor for the
      development of coronary artery disease (CAD) in healthy people and also increases
      morbidity and mortality in depressed patients with CAD. Others studies have shown
      that selective serotonin inhibitors (SSRIs) constitute a safe and effective
      treatment for depressed patients with heart disease. There are also data
      suggesting that treating depression with SSRIs has a protective role in
      myocardial infarction and may improve outcomes, including mortality.

PMID- 16457395
TI  - [From love apple to skin bouquet ... and if it also exhaled phaeromones?].
AB  - Skin exhales odours forming a bouquet which seems unique for each individual. The
      westernised socio-cultural behaviour tends to suppress them and to replace them
      by perfumes. The existence and the role of human phaeromones remain unsettled.
      Physiological and behavioural effects can be modulated by body odours and their
      putative phaeromones.

PMID- 16457394
TI  - [Physiologic requirements of high level gymnastics].
AB  - The evolution of the physiological profile of gymnasts over the past 40 years is
      outlined. Generally, gymnasts have a low aerobic aptitude in spite of an increase
      in the number of training hours. During the last decades, anaerobic power of
      gymnasts has increased. And now, the maximal power output measured by the Wingate
      test in high level male gymnasts is between 12 and 14 W.Kg-1 and in female
      gymnasts between 10 and 12 W.Kg-1. Measurement of higher blood lactate values
      also confirms that the anaerobic capacity has increased.

PMID- 16457396
TI  - [Systemic validation of clinical practice guidelines: the AGREE network].
AB  - INTRODUCTION: Over recent decades, the number of available clinical practice
      guidelines has enormously grown. Guidelines should meet specific quality criteria
      to ensure good quality. There is a growing need for the developement of a set of
      criteria to ensure that potential biases inherent in guideline development have
      been properly addressed and that the recommendations for practice are valid and
      reliable. AIM: The AGREE-collaboration is an international network that developed
      an instrument to critically appraise the methodological quality of guidelines.
      AGREE promotes a clear strategy to produce, disseminate and evaluate guidelines
      of high quality. METHOD: In the first phase of the international project the
      AGREE-instrument was tested in 11 different countries. Based on this experience
      the instrument was refined and optimised. In the second phase it was
      disseminated, promoted and evaluated in 18 participating countries. Belgium was
      one of them. RESULTS: The Belgian partner in the AGREE-project developed 3
      workshops and established 13 validation committees to validate guidelines from
      Belgian developer groups. We collected 33 questionnaires from participants of the
      workshops and the validation committees, in which we asked for primary
      experiences and information on the usefulness and applicability of the
      instrument. We were also interested in the shortcomings of the instrument and
      potential strategies to bridge them. DISCUSSION: More efforts should be made to
      train methodological experts to gain certain skills for a critical appraisal of
      clinical practice guidelines. Promoting the AGREE-instrument will lead to a
      broader knowledge and use of quality criteria in guideline development and
      appraisal. CONCLUSION: The development and dissemination of an international list
      of criteria to appraise the quality of guidelines will stimulate the development
      of methodologically sound guidelines. International comparisons between existing
      guidelines will lead to a better collaboration between guideline developers
      throughout the world.

PMID- 16457397
TI  - [Field, a randomized clinical trial of cardiovascular prevention with fenofibrate
      in type 2 diabetes].
AB  - FIELD ("Fenofibrate Intervention and Events Lowering in Diabetes") study compared
      the incidence of coronary and cardiovascular events in 4895 patients with type 2
      diabetes treated with fenofibrate (micronized fomulation, 200 mg/day) and in 4900
      patients treated with placebo. After a mean 5-year follow-up, the fenofibrate
      group did not have less coronary events (primary endpoint), neither present a
      significant reduction in cardiovascular or total mortality as compared to the
      placebo group. However, it had significantly less non-fatal myocardial
      infarctions and cardiovascular events in general as well as less coronary and
      total revascularization procedures (secondary endpoints). The higher rate of
      starting statin therapy in patients allocated placebo might have masked a larger
      treatment benefit of fenofibrate on macrovascular complications. The tolerance of
      fenofibrate was good, even in combination with statins. More surprisingly,
      fenofibrate exerted a favourable effect on microangiopathy complications, with
      less albuminuria progression and less retinopathy needing laser treatment
      (tertiary endpoints).

PMID- 16457398
TI  - Changes in vocational training for general practice.

PMID- 16457399
TI  - The editors of the Ulster Medical Journal.

PMID- 16457400
TI  - The history of neurology in Belfast: the first hundred years. Presidential
      address to the Ulster Medical Society, 13th October 2005.

PMID- 16457401
TI  - HOX genes: seductive science, mysterious mechanisms.
AB  - HOX genes are evolutionarily highly conserved. The HOX proteins which they encode
      are master regulators of embryonic development and continue to be expressed
      throughout postnatal life. The 39 human HOX genes are located in four clusters (A
      D) on different chromosomes at 7p15, 17q21 [corrected] 12q13, and 2q31
      respectively and are assumed to have arisen by duplication and divergence from a
      primordial homeobox gene. Disorders of limb formation, such as hand-foot-genital
      syndrome, have been traced to mutations in HOXA13 and HOXD13. Evolutionary
      conservation provides unlimited scope for experimental investigation of the
      functional control of the Hox gene network which is providing important insights
      into human disease. Chromosomal translocations involving the MLL gene, the human
      homologue of the Drosophila gene trithorax, create fusion genes which exhibit
      gain of function and are associated with aggressive leukaemias in both adults and
      children. To date 39 partner genes for MLL have been cloned from patients with
      leukaemia. Models based on specific translocations of MLL and individual HOX
      genes are now the subject of intense research aimed at understanding the
      molecular programs involved, and ultimately the design of chemotherapeutic agents
      for leukaemia. Investigation of the role of HOX genes in cancer has led to the
      concept that oncology may recapitulate ontology, a challenging postulate for
      experimentalists in view of the functional redundancy implicit in the HOX gene
      network.

PMID- 16457403
TI  - Goblet cell carcinoids of the appendix.

PMID- 16457402
TI  - Non-variceal upper gastrointestinal bleeding.

PMID- 16457405
TI  - Comparison of laparoscopic-assisted vaginal hysterectomy, total abdominal
      hysterectomy and vaginal hysterectomy.

PMID- 16457404
TI  - The evolution of sites of surgery.
AB  - The shift to ambulatory surgery has taken decades. The history and causation of
      the move are complex. Key enablers are recounted. The complex interchange of
      ideas, and physicians, between Belfast and Boston was important in the
      development of relevant facilitating standards. US and UK governmental and
      hospital statistics in the increase of ambulatory surgery are presented. The
      transition of surgery away from hospitals was not all plain-sailing. Insurance
      companies, governments and hospital administrators hindered and then acquiesced.
      The shift to ambulatory surgery has not resulted in increased patient morbidity
      and mortality.

PMID- 16457406
TI  - Fine needle aspiration cytology (FNAC) in the diagnosis of granulomatous
      lymphadenitis.
AB  - OBJECTIVE: To determine the final histological and clinical diagnosis of patients
      with granulomatous lymphadenitis on fine needle aspiration cytology (FNAC).
      METHOD: A retrospective cohort study was carried out over a five year period in a
      tertiary referral hospital. FNAC of 22 patients with granulomatous lymphadenitis
      was reviewed and correlated with the final histological diagnosis and clinical
      outcome. RESULTS: Fourteen cases (64%) underwent surgical biopsy for histological
      assessment. A definitive diagnosis on FNAC with ancillary investigations was
      achieved in 82% (18 out of 22) of the cases: four Hodgkin's lymphoma, two non
      Hodgkin's lymphoma (NHL), five tuberculosis (TB), two toxoplasmosis, one
      sarcoidosis and four benign reactive changes. CONCLUSION: A significant number of
      cases of FNAC diagnosed granulomatous lymphadenitis have an identifiable
      underlying cause. Patients with reactive cytological changes, who clinically
      appear benign, can avoid unnecessary surgery.

PMID- 16457407
TI  - Sudden unexpected death in infancy: place and time of death.
AB  - In recent years, many babies who die of Sudden Unexpected Death in Infancy (SUDI)
      in Northern Ireland are found dead in bed--i.e. co-sleeping--with an adult. In
      order to assess its frequency autopsy reports between April 1996 and August 2001
      were reviewed and linked to temporal factors. The day and month of death, and the
      place where the baby was found were compared to a reference population of infant
      deaths between one week of age and the second birthday. Although the rate of SUDI
      was lower than the UK average, 43 cases of SUDI were identified, and two
      additional deaths with virtually identical autopsy findings that were attributed
      to asphyxia caused by suffocation due to overlaying. Thirty-two of the 45 (71%)
      were less than four months of age. In 30 of the 45 cases (67%) the history stated
      that the baby was bed sharing with others; 19 died sleeping in an adult bed, and
      11 on a sofa or armchair. In 16 of the 30 (53%) there were at least two other
      people sharing the sleeping surface, and in one case, three. SUDI was twice as
      frequent at weekends (found dead Saturday-Monday mornings) compared to weekdays
      (p<0.02), and significantly more common compared to reference deaths (p<0.002).
      Co-sleeping deaths were also more frequent at weekends. Almost half of all SUDI
      (49%) occurred in the summer months--more than twice the frequency of reference
      deaths. While sharing a place of sleep per se may not increase the risk of death,
      our findings may be linked to factors such as habitual smoking, consumption of
      alcohol or illicit drugs as reported in case-control studies. In advising parents
      on safer childcare practices, health professionals must be knowledgeable of
      current research and when, for example, giving advice on co-sleeping this needs
      to be person-specific cognisant of the risks within a household. New and better
      means of targeting such information needs to be researched if those with higher
      risk life-styles are to be positively influenced.

PMID- 16457408
TI  - The transactions of the Belfast Medical Society, Belfast Clinical and
      Pathological Society and the Ulster Medical Society, with background notes.

PMID- 16457409
TI  - Ulster connections with Nelson and Trafalgar.

PMID- 16457410
TI  - Biliscrotum and retroperitoneal biloma: spontaneous rupture of the biliary system
      presenting as an incarcerated inguinal hernia.
AB  - Spontaneous rupture of the biliary system is a well documented condition in
      infants but is rare in adults. We report the case of a 73-year-old gentleman who
      presented with clinical signs and symptoms mimicking that of a strangulated right
      inguinal hernia. At emergency operation the scrotum was found to contain bile.
      Following radiological imaging and exploratory surgery, a large retroperitoneal
      biloma was found. We discuss the clinical signs associated with biliscrotum and
      retroperitoneal biloma and describe our operative management of this patient. We
      review the previously reported cases of these rare clinical entities. We found
      that our case exhibited similarities in terms of the age of presentation and
      presence of distal common bile duct stones. This is, to our knowledge, the only
      reported case of a patient presenting with biliscrotum secondary to the assumed
      spontaneous rupture of the common bile duct and development of a retroperitoneal
      biloma.

PMID- 16457411
TI  - Bilateral renal artery thrombosis due to heparin-induced thrombocytopenia
      thrombosis syndrome. Successful treatment with longterm application of lepirudin.

PMID- 16457412
TI  - Epidemic jaundice: Harvard's 5th General Hospital at Musgrave Park in World War
      II.

PMID- 16457413
TI  - Air raids.

PMID- 16457414
TI  - A rash imposition from a lifestyle omission: a case report of pellagra.

PMID- 16457415
TI  - Benign signet ring cells in the subserosa of the small intestine: a
      pseudoneoplastic phenomenon.

PMID- 16457416
TI  - The choice for sons or daughters.

PMID- 16457417
TI  - What is an error?

PMID- 16457418
TI  - Psychophysiological and subjective sexual arousal to visual sexual stimuli in new
      women.
AB  - Conflicting data exist regarding the sexual arousal patterns of post-operative
      male-to-female (MTF) women with Gender Identity Disorder. The purpose of this
      study was to examine objective and subjective aspects of the sexual arousal
      response using a vaginal photoplethysmograph. Fifteen MTF women viewed neutral
      and erotic audiovisual film segments while their blood flow patterns were
      monitored. Subjective measures of affect and sexual arousal were taken before and
      immediately after the films. There was a significant increase in self-reported
      subjective arousal, perceived genital arousal, perceived autonomic arousal, and
      positive affect; however, movement artefacts interfered with our assessment of
      the genital arousal response. MTF women reported both low levels of pain and low
      levels of awareness of the vaginal probe during testing. These data are discussed
      in the context of differences in pelvic musculature between natal and new women
      and have implications for future studies that aim to measure sexual arousal
      objectively in MTF women.

PMID- 16457419
TI  - Vulvar vestibulitis syndrome: an important factor in the evaluation of lifelong
      vaginismus?
AB  - The aim of the study was to investigate the prevalence of vulvar vestibulitis
      syndrome (VVS) in a sample of women suffering from lifelong vaginismus (N=91).
      Lifelong vaginismus is defined as "having a history of never having been able to
      experience penile entry of the vagina". The results with respect to VVS are
      compared with the results of women who are suffering from pain during intercourse
      (superficial dyspareunia) (N=84). Both patients groups were recruited from two
      treatment outcome studies. Using a standard physical examination, erythema was
      found in 77%, pain "on touch" in 69% and erythema and pain on the same location
      was seen in 56% of the patients with lifelong vaginismus. Furthermore, it was
      found that erythema (94%), pain (98%) and erythema and pain on the same location
      (92%) were more frequently found in patients with dyspareunia compared to women
      with lifelong vaginismus. It is concluded that pain is an integral part of the
      experiences in the majority of women with lifelong vaginismus.

PMID- 16457420
TI  - Vestibulodynia (former vulvar vestibulitis): personality in affected women.
AB  - AIM: There are very few studies regarding the personality in women suffering from
      vestibulodynia. Our former results showed increased levels of depression and
      state anxiety in these women (and their partners). In order to optimize treatment
      of these patients we wanted to assess personality and its association with
      depression and anxiety. METHODS: Thirty women attending the vulva clinic for the
      first time were included at the time of diagnosis (vestibulodynia). The
      Temperament and Character Inventory (TCI) was administered to assess personality,
      Beck's Depression Inventory (BDI) to assess depression, State Anxiety Inventory
      (STAI-S) to assess anxiety, and a questionnaire to assess clinical results.
      RESULTS: Results showed that women with vestibulodynia have a personality profile
      with specific temperament and character traits. The results on the TCI
      temperament dimension characterized them as cautious, careful, insecure, and
      pessimistic. Results on the TCI character dimension indicated them to experience
      their own behavior and choices influenced out of their control or against their
      own will. The interaction of these factors may form a personality profile,
      resulting in an increased vulnerability in intimate relations and it could also
      be an important factor for state of depression and anxiety. CONCLUSIONS: The
      present results indicate the importance of identifying psychological factors in
      order to optimize the care of vestibulodynia patients and to relieve their
      symptoms and improve their situation. We therefore want to emphasize that
      vestibulodynia patients should always, in addition to medical examination and
      treatment, also be psychologically examined.

PMID- 16457421
TI  - Alexithymia and body image disturbances in women with Premenstrual Dysphoric
      Disorder.
AB  - BACKGROUND: To evaluate alexithymia and body image in women with Premenstrual
      Dysphoric Disorder and test whether alexithymic traits influence severity of
      Premenstrual Dysphoric Disorder or body distress. METHODS: Sixty-four consecutive
      women with a DSM-IV diagnosis of Premenstrual Dysphoric Disorder and age range of
      18-45 were recruited. Alexithymia was measured with the Italian version 20-items
      Toronto Alexithymia Scale. Severity of premenstrual mood symptoms was measured
      through the use of Visual Analogue Scales. Body concerns were assessed with the
      Body Uneasiness Test, Body Shape Questionnaire and Body Attitude Test. Additional
      measures were Rosenberg Self-Esteem Scale and Sheehan Disability Scale. RESULTS:
      Prevalence of alexithymia in our sample was 31.3% (n=20). Alexithymics showed
      higher scores on all rating scales (p range 0.001-< 0.001). Difficulty in
      Identifying Feelings and Difficulty in Describing Feelings subscales of Toronto
      Alexithymia Scale were predictors of severity of Premenstrual Dysphoric Disorder
      in the multiple linear regression analysis. CONCLUSIONS: Alexithymia was
      associated with more severe Premenstrual Dysphoric Disorder. Alexithymic women
      with Premenstrual Dysphoric Disorder exhibited significantly poorer appearance
      evaluation and body satisfaction than non-alexithymic women.

PMID- 16457422
TI  - Is blood really thicker than water? Assisted reproduction and its impact on our
      thinking about family.
AB  - The traditional notion that a family is built around and based on blood or
      genetic ties is challenged when assisted human reproduction utilizing donor
      gametes is used. A focus on the family--in contrast to the individual--requires
      from medicine an extension of thinking in which a model that incorporates
      treating infertility and building a family becomes the norm. Such a model will
      require that attention is given to the psychological and social needs of the
      would-be parents, thus enabling them to approach their family building with
      confidence. This confidence is expected to carry through to their sharing with
      their offspring the nature of their family building and thus avoid the stigma
      that leads to secrecy. Research relating to dimensions of family building when
      donor insemination has been used is reviewed. The impact of professional
      attitudes, along with the policies adopted by governments concerning access to
      genetic information for offspring, significantly influences the families built
      with assistance of donor gametes or embryos. The evolution of professional
      thinking in this area is reviewed, along with the increasing involvement of
      governments.

PMID- 16457423
TI  - The effects of acute relaxation on indices of anxiety during pregnancy.
AB  - OBJECTIVES: Antenatal maternal anxiety has adverse effects on the fetus and the
      child. In this study we determined whether a short period of directed or of
      passive relaxation reduced maternal self-rated anxiety, heart rate, plasma
      catecholamines, cortisol and uterine artery resistance index, in pregnant women.
      METHODS: Fifty-eight women (28-32 wks gestation) were assigned randomly to a
      session of directed active or passive (sitting quietly) relaxation. Spielberger
      self-rating anxiety questionnaires were completed, and a venous blood sample
      taken, before and after a Doppler scan. RESULTS: Both active and passive
      relaxation significantly reduced State Anxiety and maternal heart rate, but the
      effect was significantly greater with the active relaxation. In contrast, the
      passive relaxation significantly reduced noradrenaline levels whereas active did
      not. Adrenaline levels were not changed significantly with either type of
      relaxation. Both methods significantly reduced cortisol, with a trend for the
      passive to have a greater effect. The active relaxation had no effect on uterine
      artery blood flow, whereas there was a statistically significant, but clinically
      negligible, increase in mean resistance index after passive relaxation.
      CONCLUSION: Both methods reduced maternal State Anxiety and heart rate, the
      active method more so. However there was a striking lack of correlation with the
      other biological indices studied. In order to reduce specific biological effects
      of anxiety during pregnancy, different methods may be needed from those which are
      most effective at reducing subjective anxiety.

PMID- 16457424
TI  - A longitudinal pre-pregnancy to post-delivery comparison of genetic and
      gestational surrogate and intended mothers: confidence and genealogy.
AB  - For women opting to use surrogacy to overcome subfertility, a choice can be made
      to have a genetically related or unrelated baby. Similarly, women opting to
      become surrogate mothers also have to choose to gestate and relinquish a
      genetically related or unrelated baby. This study explored the cognitions behind
      the initial choices made and determined the strength of those cognitions six
      months post-delivery of the surrogate baby. Surrogate and Intended mothers (N=81)
      undergoing Artificial Insemination (AI, genetic) or Embryo Transfer (ET,
      gestational) were studied separately (four groups) at the start of their
      surrogate arrangement and those with a positive outcome (n=34) were re
      interviewed at six months post-relinquishment. There were significant differences
      between surrogate and intended mothers in their confidence about the arrangement.
      Beliefs about the importance of a genetic link were predictors of ET
      arrangements. Responses were consistent over a one and a half-year study period.
      The ethical and clinical implications of the results are discussed in relation to
      appropriate self-selection and confidence with the surrogate process and the
      importance of genetic offspring.

PMID- 16457425
TI  - The end of the affair.

PMID- 16457426
TI  - Descriptive epidemiology of malignant mesothelioma.
AB  - BACKGROUND: Malignant mesothelioma (MM) is a rare cancer associated with exposure
      to asbestos, whose occurrence is increasing in industrialized countries.
      OBJECTIVES: Describe and discuss: determinant factors, natural history, epidemic
      pattern, burden of MM to society at large, where interventions should be directed
      to change MM occurrence, gaps in knowledge. METHODS: Review of the literature.
      Description of MM epidemiological features, with emphasis on risk, prognosis,
      control measures. RESULTS: MM may be associated with low level asbestos exposure.
      Natural fibres other than asbestos possess the same carcinogenic potency. The
      estimated mean induction period is 25 years, and can be as long as 60 or more
      years. Survival is poor; current rates of MM in industrialized countries mirror
      past use of asbestos. In the USA, MM incidence increased steeply from the 1970's,
      peaked in 2000-2004, then levelled off and is expected to return to background
      levels by 2055. In the same period, the time-pattern for females was constant.
      Questions remain unanswered about the contribution of environmental asbestos
      exposure to MM occurrence. A gender effect has been described. The role of
      genetic and familial susceptibility is suggested by studies in Turkey. Sv40 has
      been proposed as co-factor in the asbestos-MM association. Controversy about the
      different hazards of different asbestos forms is still strong. CONCLUSIONS: World
      production of asbestos has been declining dramatically in recent years, however
      increases have occurred in Asia. The decrease in asbestos use and a ban in
      several industrialized countries have proved effective in reducing the societal
      burden of MM.

PMID- 16457427
TI  - Nordic experience: expected decline in the incidence of mesotheliomas resulting
      from ceased exposure?
AB  - BACKGROUND: As a result mainly of information to workers and the public on
      prevention of effects of asbestos exposure, the use of asbestos for insulation
      was reduced to a minimum in the Nordic countries during the second half of the
      1970's and the early 1980's. Stringent regulations when handling asbestos were
      introduced, and prohibition of use began in the early 1980's. Depending on the
      duration of the latency period between first exposure and the period of most
      intense exposure, a decline might be expected in the incidence of Malignant
      Mesothelioma (MM) 20-45 years after interruption of exposure. OBJECTIVES: to
      describe the incidence of MM after cessation of asbestos exposure in Nordic
      countries. METHODS: Nordic countries have cancer registers with information on
      all new cases of all cancers, over the past 4-6 decades. Cancer incidence data in
      these registers could describe long-term effects of interruption of asbestos
      exposure. RESULTS: Current male and female incidence in Norway is about 1.5 x 10(
      5)/year and 0.2 x 10(-5)/year respectively, and appears to be increasing. Based
      on personal observations among 32 MM cases, a number of which resulting from low
      total asbestos exposure with mean latency of about 45 years, examples are
      presented of the MM incidence in Nordic countries, illustrating when a
      significant decline in MM incidence may be expected. CONCLUSIONS: 25 years after
      interruption of asbestos exposure, the expected rapid decline in MM incidence is
      still lacking, which appears to agree with population-based selection phenomena,
      with survival of a large pool of asbestos-exposed subjects with minimal exposure.

PMID- 16457429
TI  - Mesothelioma associated with environmental exposures.
AB  - BACKGROUND: The main sources of environmental, non-occupational exposure to
      asbestos or asbestiform fibres are: a) industrial plants in which asbestos was
      used in the production process; b) asbestos "in place" (mainly in buildings); c)
      contaminated soils. The association of these exposures with increasing risk of
      mesothelioma has been documented since 1960 in many places. OBJECTIVES AND
      METHODS: The present paper is aimed at describing the main results of studies
      performed in the locations with soils naturally contaminated with asbestos or
      asbestiform fibres. Environmental exposure data and asbestos-related health
      outcomes, mainly mesothelioma, are analyzed through a review of the literature.
      RESULTS: The sites with asbestos or other mesotheliomatogenous fibres in soils
      are characterized by low concentration levels of airborne fibres. Furthermore,
      exposure levels may increase when specific activities are carried out (mainly
      related to building construction), involving mechanical disturbance of fibre
      containing materials. The type of fibres found are mainly amphiboles (tremolite).
      The population at risk of exposure is the general population, which can be
      exposed from birth. In these sites, the sex ratio of mesothelioma cases is close
      to 1.0 and the average age of cases ranges from 50 to 60 years. CONCLUSIONS: Both
      "natural"and industrial environmental asbestos or asbestiform fibre exposures
      increase potential risk for mesothelioma. Strategies of environmental reclamation
      and risk communication should be implemented in these areas.

PMID- 16457428
TI  - Malignant mesothelioma and the working environment: the viewpoint of the
      occupational physician.
AB  - BACKGROUND: Firm scientific evidence supports the causal association between
      malignant mesothelioma (MM) and occupational exposure to asbestos. Risk
      attributable to occupation varies from 30 to 80% across different populations.
      The existence of a threshold level below which there is no risk of MM is still
      debated. A prompt and thorough assessment of exposure is essential to evaluate
      and manage MM cases, from diagnostic and epidemiological points of view.
      OBJECTIVES AND METHODS: To highlight the multiple areas of intervention by
      Occupational Physicians (OP) in MM evaluation and management, to describe an
      experience of OP in the province of Brescia. RESULTS: The main areas of interest
      of the OP are exposure assessment, diagnosis (clinical, etiological), medico
      legal issues, social consequences, preventive strategies, risk communication,
      scientific dispute/uncertainties. By means of an active search, the Brescia MM
      registry, managed by OP belonging to the local health authority observed 309 MM
      from 1977 to 2003; the local Institute of Occupational Health, hosted in a
      hospital of national relevance, evaluated about 200 MM in the last decade. The
      main outcomes of OP activity are the high percentage of direct interviews,
      individual case management, expert exposure assessment, etiological diagnosis,
      counselling, medico-legal assistance, better knowledge of occupational risks,
      enhanced cooperation among health professionals (oncologists, pathologists,
      surgeons, pneumologists, general practitioners and OP), important contribution to
      Registries and to epidemiology (estimates of attributable risks, incidence,
      survival rates), with positive social and scientific consequences (insurance
      agencies, trade union organizations, public events, teaching opportunities).
      CONCLUSIONS: This experience highlights the multifaceted role of OP in active
      research and evaluation of MM cases, in the context of a multidisciplinary
      approach.

PMID- 16457430
TI  - Epidemiologic surveillance for primary prevention of malignant mesothelioma: the
      Italian experience.
AB  - BACKGROUND: The Italian National Mesothelioma Registry (ReNaM) was set up at the
      National Institute for Occupational Safety and Health (ISPESL) to estimate
      Italian incidence of malignant mesothelioma (MM), define modalities of asbestos
      exposures, assess impact and diffusion of MM, identify underestimated sources of
      environmental contamination. OBJECTIVES: To describe ReNaM activity, database
      dimension and epidemiological characteristics of the caselist. METHODS: Regional
      Operating Centers (COR) in 16 Italian regions were set up to identify and
      investigate all cases of MM diagnosed in each region, applying national
      guidelines. COR collect cases in health care institutions. Occupational history,
      lifestyle and residence are obtained by direct interview using a standard
      questionnaire. Exposure modalities are classified by industrial hygienists,
      evaluating whether work, private life or any particular environmental condition
      could have involved asbestos exposure. RESULTS: Data refer to 3,446 cases
      collected in 9 Italian regions during 1993-2001. Pleural mesothelioma affected
      94% cases, pleural/peritoneal ratio was 16:1. Gender ratio (M/F) was 2.7:1 (1.3:1
      for peritoneum). There was a variety of occupational exposures, some already
      known as high risk sectors and others unexpected. The most common exposures
      occurred in building and construction, metallurgy and steel, shipbuilding, and
      railway stock. High risk categories were encountered such as bricklayers,
      plumbers, carpenters, electricians, welders, installers and maintenance workers
      in metallurgy and the steel industry, general labourers, tool makers and painters
      in shipbuilding/repair/demolition. CONCLUSIONS: Despite some ReNam's limitations,
      identification of MM cases and analysis of modality of exposure, with
      standardized criteria, are a fundamental tool for primary prevention of asbestos
      related diseases.

PMID- 16457431
TI  - SV40, genetic polymorphism and mesothelioma. pathological and epidemiological
      evidence.
AB  - BACKGROUND: Asbestos exposure is the only cause of epidemiological relevance for
      pleural malignant mesothelioma (MM), but the mechanism of action is not entirely
      understood. A causal role was suggested for SV40 since viral DNA and proteins
      were detected in pleural MM and SV40 caused MM in hamsters. SV40 proteins (Tag)
      interact with oncogenes P53 and Rb. OBJECTIVES: To review evidence on the
      association of SV40 with MM, bearing in mind laboratory and epidemiological
      studies. METHODS: The review on SV40 was based on scientific papers published
      since 1990 on association of SV40 with human cancer. RESULTS: Studies researching
      SV40 DNA in MM tissue observed a wide range of prevalences (0% to 70%); causes of
      variability were not convincingly identified. An association of MM with SV40 was
      suggested but confounding factors and biases were not considered. Cohort studies
      on humans inoculated with contaminated vaccines did not show an increased
      incidence but their statistical power was limited. Diffusion of SV40 in humans is
      linked to polio vaccines produced in 1955-63 from SV40-infected monkeys. A 11-12%
      prevalence of SV40 in adults were reported in the USA, 2-6% in Europe and Africa.
      The age pattern of MM does not suggest a cohort effect related to contaminated
      vaccines. DISCUSSION: Association of SV40 with human MM is suggested from
      laboratory observations but still lacks confirmation in well designed
      epidemiological studies. Other putative co-factors in MM occurrence are mutations
      in genes involved in repair of damage caused by asbestos, notably DNA-repair
      genes. Preliminary observations are available but epidemiological studies are
      needed to test this hypothesis.

PMID- 16457432
TI  - Peculiar features of mesothelioma occurrence as related to exposure patterns and
      circumstances in the Lombard Region, Italy.
AB  - BACKGROUND: The "Lombardy Mesothelioma Registry" started its activity in 2000 in
      accordance with Italian law DL 277/91. OBJECTIVES AND METHODS: The Registry
      collects all new incident cases of Malignant Mesothelioma (MM) of pleura,
      peritoneum, pericardium and vaginal tunic of testis occurring in residents in the
      Lombardy Region (Northern Italy). For each "possible case" reported to the
      Registry by Lombardy hospitals, diagnosis is ascertained according to ISPESL
      Guidelines. For confirmed cases, a standardized questionnaire is administered to
      the subject or next-of-kin, to verify sources of lifetime asbestos exposure.
      Descriptive results are given for cases collected in 2000-2001. Age standardized
      incidence rates for the year 2000 were calculated for males and females. RESULTS:
      After revision of clinical records, diagnosis was judged as "certain" MM in 307
      (60%) subjects, probable in 63 (12%) and possible in 33 (6%) subjects. 21 were
      peritoneal mesothelioma. Standardized rates for pleural mesothelioma were
      respectively 3.7 and 1.4 per 100,000 for males and females. Occupational asbestos
      exposure was ascertained for 71% of male cases and 26% of females. Exposure was
      unknown in 11% and 27% of males and females respectively. The main relevant
      exposures were in building trades, metal manufacturing, machine production and
      maintenance; an unexpectedly high proportion of female cases was engaged in non
      asbestos textile factories. CONCLUSIONS: The high proportion of cases with
      unknown exposure underlines the need to explore new tools and sources to
      ascertain asbestos exposure. An ad hoc survey in textile industries showed
      exposure to asbestos to be widely spread in this industry.

PMID- 16457433
TI  - Malignant mesothelioma in 2004: How advanced technology and new drugs are
      changing the perspectives of mesothelioma patients. Highlights from the VIIth
      Meeting of the International Mesothelioma Interest Group.
AB  - Malignant mesothelioma (MMe) is a seemingly uncommon tumour whose incidence has
      in fact increased steadily and progressively over the last 30 years. Indeed, an
      actual "epidemic" is expected in the next 20 years, with over 1300 new cases a
      year till 2020 at least. Despite unquestionable improvement in the diagnostic
      methods at our disposal and the availability of new treatment strategies, the
      prognosis of MMe patients remains dramatically poor. For all the above reasons,
      translational research is the key to success; indeed, ever increasing knowledge
      of the molecular mechanisms underlying MMe pathogenesis could lead (and is
      actually leading) to new, hopefully more active, treatment options. To foster
      discussion among investigators working in this field, and to exchange different
      viewpoints concerning the newest advances in MMe pathogenesis and treatment, the
      VII International Mesothelioma Interest Group (IMIG) meeting was held in Brescia
      (Italy) between 24 and 26 June 2004 in cooperation with the Italian Group for the
      Study and Therapy of MMe (GIMe). The aim of this report is to summarize the most
      significant advances in the different disciplines applied to MMe presented and
      discussed during the IMIG meeting and how these advances will be changing the
      perspective of patients with MMe.

PMID- 16457434
TI  - [Polarized microscopic observation of the collagen change in bone healing during
      bone lengthening].
AB  - OBJECTIVE: To investigate the feature and regularity of the collagen change in
      bone healing during bone lengthening. METHODS: Bone lengthening model was made in
      the middle segment of the rabbit tibia. Five days after the model was
      established, the bone was lengthened 1.5 mm per day for 14 days. The rabbits were
      put to death after elongation, 7, 14, 21, 30, 40, 50, 60 and 70 days after
      elongation. The distracted area of the bone was imbedded with paraffin. After
      being stained by the picric acid-sirius red staining, the slice was observed
      under polarized microscope. RESULTS: The features of the collagen change in the
      distracted bone were as follows: (1) In the fibrous tissue of the distracted area
      during lengthening period and the early stage after lengthening, there was not
      only collagen III but also much collagen I. (2) Collagen I , II and III were
      observed in the cartilage. (3) Collagen I, II and III were also observed in the
      pseudo-growth plate. (4) Collagen I took the dominance during lengthening period
      and the late stage after lengthening. CONCLUSION: New bone formation in bone
      lengthening is under the distracted force, so the collagen changes have different
      features compared with that in fracture healing. Collagen I, II and III can be
      identified by picric acid-sirius red staining and polarized microscope, so a new
      method for studying the collagen typing in bone repairing is provided.

PMID- 16457435
TI  - [The study on biocompatibility of diamond-like carbon coated nickel-titanium
      shape memory alloy with osteoblasts cultured in vitro].
AB  - OBJECTIVE: To investigate the biocompatibility of diamond-like carbon (DLC)
      coated Nickel-Titanium shape memory alloy with osteoblasts cultured in vitro.
      METHODS: Rabbit's osteoblasts were incubated with DLC-coated Nickel-Titanium
      shape memory alloy disks and uncoated ones of equal size for 5 days. The control
      group (without shape memory alloy in culture media) was performed simultaneously.
      The cultured cells were counted and graphed. The samples from culture media were
      collected and the concentrations of alkaline phosphatase (ALP) and nickel (Ni2+)
      were measured from the 1st to 5th day respectively. RESULTS: The proliferation of
      osteoblasts and the concentration of ALP in both DLC-coated group and control
      group was higher than uncoated group. The proliferation of osteoblasts on the
      3rd, 4th, and 5th day in both DLC-coated group and control group was
      significantly higher than that in the uncoated group (P < 0.05). The
      concentration of ALP in DLC-coated group on the 2nd, 3rd, and 5th day and in the
      control group on the 3rd, 4th, and 5th day was significantly higher than that in
      the uncoated group (P < 0.05). The concentration of Ni2+ on the 3rd, 4th, and 5th
      day was significantly lower than that in the uncoated group (P < 0.05).
      CONCLUSION: DLC- coated Nickel-Titanium shape memory alloys appears to have
      better biocompatibility with osteoblast cultured in vitro compared to uncoated
      ones.

PMID- 16457436
TI  - [Cloning of NEP1-40 gene and expression of its protein].
AB  - OBJECTIVE: To clone the genes of nogo-66 and NEP1-40 from spinal cord of rat and
      to realize the expression of its protein in vitro. METHODS: The nogo-66 and NEP1
      40 genes were cloned from the spinal cord of juvenile rat by use of RT-PCR
      techniques, and the objective genes were bonded to T vector through gene coupled
      action, recombinant plasmid were sequencing, and the genes were cloned into PQE30
      GST vector, then the recombinant plasmids were induced by isopropyl
      thiogalactoside (IPTG) to express the proteins. The two proteins were purified by
      Ni-column and detected by using Western-blot test. RESULTS: The Nogo-66 and NEP1
      40 genes were successfully cloned from rat, which were 215 bp and 137 bp for each
      one when add the enzyme site. No gene mutations were detected in the two genes
      after sequencing. The expression plasmids were cut by the two enzyme (BamH I and
      Hind III), the target bands were seen on the results of electrophoresis. The
      expression plasmids were induced by IPTG and got the purified GST fusion protein
      nogo-66 and NEP1-40, which relative molecular weight were 33.2 x 10(3) and 30.3 x
      10(3) respectively. The results of Western-blot test confirmed that the
      antigenicity of the two proteins was precise. CONCLUSION: Nogo-66 and NEP1-40
      proteins can be expressed in a high efficiency in vitro using genetic
      engineering, so it provides a good basis for further research on its function and
      vaccine for spinal injury.

PMID- 16457437
TI  - [The effect of the plantar plate and the collateral ligaments on the flexion of
      the metatarsophalangeal joints].
AB  - OBJECTIVE: To explore the effect of the collateral ligaments and the plantar
      plate on the flexion of the metatarsophalangeal (MP) joints. METHODS: Twenty-four
      preserved human No. 2-4 digits were obtained from embalmed cadaver feet, which
      were divided into 2 groups at random. In group A, the bilateral collateral
      ligaments were cut first, and then the plantar plate was sectioned. They were cut
      in opposite sequence in group B. Angle of the flexion of MP joint was observed in
      the same load after the bilateral collateral ligaments and the plantar plate were
      sectioned in different sequence. From 1994 to 2000, 11 cases were used with this
      technic, including plantar section in 2 cases and both plantar section and
      bilateral collateral ligaments cut in 9 cases. RESULTS: The angle of flexion of
      the MP joint before operation in group A is 37.30 +/- 5.42 degrees, it increased
      11.29 +/- 2.36 degrees and to 48.60 +/- 2.98 degrees when the bilateral
      collateral ligaments were cut, and there was significant difference. Later the
      cut of the plantar plate increased another 5.30 +/- 1.59 degrees and to 53.35 +/-
      2.76 degrees. Both have an increasing trend for the angle of flexion of the MP
      joint (P < 0.01). While in group B, the angle of flexion of the MP joint before
      operation is 34.59 +/- 5.32 degrees, it increased 6.29 +/- 2.98 degrees and to
      40.89 +/- 2.36 degrees when the plantar plate were cut, later the cut of the
      bilateral collateral ligaments increased another 9.71 +/- 1.94 degrees and to
      50.60 +/- 2.01 degrees. Both had an increasing trend for the angle of flexion of
      the MP joint (P < 0.01). The bilateral collateral ligaments had more influence
      than the plantar plate (P < 0.01). There was the same effect in different
      sequence (P > 0.05). In 2 cases with plantar section, the flexion angle of MP
      joint could achieve 15 degrees to 45 degrees in 2 months. The other 9 cases with
      both plantar section and bilateral collateral ligaments cut, the MP joint flexion
      achieved 10.3 degrees to 58.4 degrees in 26.3 months. CONCLUSION: The flexion
      angle of the MP joint can be increased by cutting the bilateral collateral
      ligaments and the plantar plate.

PMID- 16457438
TI  - [Evaluation of the effect of triple arthrodesis on treating complications of
      calcaneus].
AB  - OBJECTIVE: To evaluate the effect of triple arthrodesis on treating complications
      of calcaneus fractures. METHODS: From 1990 to 2001, 12 patients with the
      complications of calcaneus fractures underwent the triple arthrodesis (subtalar,
      talaronavicular and calcaneocuboid joints). Ollier incision was applied to all
      patients. Peroneal tenolysis was required in 2 patients and a decompression and
      transposition of tibial-nerve in 1 patient. Of the 12 patients, 7 were males and
      5 were females. Their ages ranged from 29 to 64 years. Complications, like pain
      and deformity, occurred 5 to 22 months after the operation(18 months on average).
      Preoperative score, fibulocalcaneal distance, Bohler angle, difference of talar
      declination angle and height of hind foot were 40.00 +/- 5.22, 0.41 +/- 0.03 cm,
      12.00 +/- 3.40 degrees, 17.00 +/- 3.32 degrees and 4.12 +/- 0.35 cm respectively.
      RESULTS: All patients were followed up from 3 to 13 years with an average of 7
      years. Postoperative score, tibulocalcaneal distance, Bohler angle, difference of
      talar declination angle and height of hind foot were 75.00 +/- 6.46, 0.73 +/-
      0.02 cm, 31.00 +/- 5.61 degrees, 9.00 +/- 3.15 degrees and 6.75 +/- 0.62 cm
      respectively. There were significant differences in these indexes(P < 0.05).
      CONCLUSION: To evaluate the complications of calcaneus fractures and to adopt
      proper operative procedures are necessary. To restore the height of hind foot and
      the anatomical relationship between hind foot and calcaneus is the key factor to
      success.

PMID- 16457439
TI  - [Reconstruction of calcaneal thalamus by bone autograft and subtalar arthrodesis
      for antiquated intra-articular calcaneal fractures].
AB  - OBJECTIVE: To introduce a clinical treatment for the reconstruction of calcaneal
      thalamus by bone autograft and subtalar arthrodesis for antiquated intra
      articular calcaneal fractures. METHODS: From July 2000 to October 2003, 11 cases
      with antiquated intra-articular calcaneal fractures were treated. Of the 11
      cases, 9 were males and 2 females,whose ages ranged from 21 to 48 years. All
      unilateral calcanei were involved in the 11 cases. The modified extended L-shaped
      approach lateral to calcaneus was adopted. The primary treatment was manipulation
      and immobilization with the reconstruction of calcaneal thalamus by bone
      autograft and subtalar arthrodesis. The average volume of the ilium for the
      autograft was 3.0 cm x 2.5 cm x 1.8 cm. Protruded osteophyte from the lateral
      wall of calcaneus were ablated in all 11 cases. RESULTS: All the 11 cases were
      followed up for 3 to 18 months, 11.5 months on average. The reconstructed
      calcaneal thalamus was healed 10 to 12 weeks after the operation. Some of the
      patients could walk with load 8 weeks after the operation, and the average time
      for all the patients to walk with load was 13.2 weeks. There were 4 cases of
      excellent result, 5 cases of good result, and 2 cases of fair result, according
      to ZHANG Tieliang's foot score system. Plain radiograph showed that Bohler angle,
      width of calcaneus and height of calcaneal thalamus were nearly restored to
      normal. CONCLUSION: With the improvement of calcaneal abnormality and restoration
      of the shape and function of hind foot, reconstruction of calcaneal thalamus by
      bone autograft combined with subtalar arthrodesis is effective in treating
      antiquated intra-articular calcaneal fractures.

PMID- 16457440
TI  - Comparative study on the effect of reamed and nonreamed intramedullary nails on
      treating open tibial fractures.
AB  - OBJECTIVE: To compare the clinical effect of reamed and nonreamed intramedullary
      interlocking nails on treating open tibial fractures. METHODS: From February 2002
      to February 2004, 92 cases of open tibial fractures (86 patients) were treated
      with intramedullary interlocking nails. Of the 86 patients, 65 were male and 21
      were female. Their age ranged from 18 to 68 years (36.5 on average). Of the 92
      cases, 54 were in the reamed group and 38 in the nonreamed group. Patients moved
      with the support of crutch after their wounds were healed. RESULTS: All patients
      were followed up regularly for 6 to 24 months. Infection rate in the reamed group
      and nonreamed group was 20.3% and 5.3% respectively, and there was significant
      difference between them (P < 0.05). The average healing time of the fractures was
      22.5 weeks in reamed group and 19 weeks in nonreamed group, and there was no
      significant difference between them (P > 0.05). Delayed unions occurred in 8
      cases and 3 cases in reamed group and nonreamed group respectively. CONCLUSION:
      Compared with reamed group, nonreamed intramedullary interlocking nails have
      lower infection rate and fewer delayed unions and unions.

PMID- 16457441
TI  - [Transplantation of the cutaneous iliac flap for the repair of bone and soft
      tissue defect of metatarsal].
AB  - OBJECTIVE: To investigate the effect of transplantation of the cutaneous iliac
      flap on repairing bone and soft tissue defect of metatarsal. METHODS: From
      October 1999 to December 2003, the cutaneous iliac flap was designed for the
      repair of bone and soft tissue defect of metatarsal in 4 male patients, whose
      ages ranged from 26 to 47, with skin graft for the coverage of the iliac flap.
      The duration of injury ranged from 1 to 5 months. The length of the defect ranged
      from 4 to 7 cm and the defect area ranged from 5 cm x 3 cm to 9 cm x 5 cm.
      RESULTS: One week after transplantation, complete survival of iliac flap was
      observed in 3 cases and partial survival in 1 case (but later proved survived).
      Callus was seen 1 month after transplantation and K-wires were removed 4 months
      after transplantation. Patients were followed up for 5 to 24 months. There were
      no ulcers. The ability of walking and bearing was satisfying as well as the
      function and shape. CONCLUSION: With satisfying restoration of function and
      shape, transplantation of the cutaneous iliac flap with skin graft is an
      alternative to treat bone and soft tissue defect of metatarsal with one stage
      surgery.

PMID- 16457443
TI  - [Repair of flexor contracture of the hand].
AB  - OBJECTIVE: To investigate the etiology of the flexor contracture of the hand, to
      diagnose and to explore its surgical treatment. METHODS: From May 1997 to June
      2004, 212 cases of flexor contraction of the hand were treated with scar
      excision, thorough loosening the contracture, covering the secondary skin defects
      with free skin grafting, "Z"-plasty, double "V-Y" plasty, transposition of the
      palmar dorsum flap of the hand and iliac-inguinal flap. There were 163 males and
      49 females, whose ages ranged from 3 to 61. There were 85 cases of left hands, 54
      cases of right hands, and 73 cases of both hands. Contracture sites were as
      follow: 117 cases were in fingers, 32 cases located in palms and 63 cases were in
      both. Causes of deformity were as follow: 29 cases derived from burn and
      explosion, 127 cases came from contracture of palmar aponeurosis, 31 cases were
      because of traffic accident and machine extrusion, 5 cases for getting an
      electric shock, 14 cases for improper postoperative immobility, and 6 cases for
      other reasons. Course of diseases lasted for 2 to 24 months. RESULTS: 149 cases
      were followed up for 4 to 30 months. One fingertip was in necrosis and ended in
      nub plasty because of inappropriate time to leave hospital. Flexion contracture
      recurred in 7 cases, skin necrosis occurred to 3 cases whose scars were healed in
      the end, poor restoration of function was observed in 2 children patients for
      lack of exercise, and 2 skins contracted after free cut skin grafting. Others got
      satisfactory results. CONCLUSION: Once the pathogenesis and contracture factors
      are clearly known, timing and correct surgical measures are chosen, thorough
      contracture is loosened, and early postoperative exercises are performed, good
      effect will be achieved.

PMID- 16457442
TI  - [The effect of limb salvage on treating osteosarcoma with pathological fracture
      in two cases].
AB  - OBJECTIVE: To investigate the effect of limb salvage on treating osteosarcoma
      with pathological fracture. METHODS: From October 2002 to January 2003, 2 cases
      of osteosarcoma with pathological fracture were treated by limb salvage. Intra
      arterial chemotherapy was given by subcutaneous implantable delivery system with
      caffeine. Replacement with prosthesis was performed after 5 times of
      chemotherapy. RESULTS: Two patients were followed up for twenty-four months and
      21 months respectively. No infection, aseptic loosening, local recurrence or
      metastasis occurred, and function recovery of joints was satisfactory.
      CONCLUSION: Limb salvage can be considered in condition that primary osteosarcoma
      with pathological fracture can be treated by effective and comprehensive
      chemotherapy.

PMID- 16457444
TI  - [Repair the palmar soft tissue defect of the finger with cross-finger flap with
      cutaneous branch of the ulnar digital finger].
AB  - OBJECTIVE: To discuss the clinical effect of cross-finger flap with cutaneous
      branch of the ulnar digital finger on repairing the palmar soft tissue defect of
      the finger. METHODS: From October 1996 to June 2004, cross-finger flaps were used
      to repair the palmar soft tissue defect of the finger in 25 cases (32 fingers )
      with tendon or bone exposed. There were 18 males and 7 females, and their ages
      ranged from 13 to 45 years. Among them, 6 cases were incised injury, 8 cases were
      impact and press injury, 11 cases were crush injury; and 2 cases were thumb, 8
      cases were index, 5 cases were middle finger, 3 cases were ring finger, 2 cases
      were little finger, 2 cases were index and middle finger, 2 cases were middle and
      ring finger, and 1 cases were index, middle, ring and little finger. The time
      from injury to diagnosis was 30 min to 48 h, and the size of the tissue defect
      was 1.5 cm x 1.0 cm to 4.1 cm x 2.0 cm. All cases were treated with emergent
      operation, and the sense of the flap was recovered by anastomosing the cutaneous
      branch of the ulnar digital finger and the distal digital nerve of injured
      finger. The flap pedicle was dissected 3 weeks later. RESULTS: Follow-up was
      conducted for 6 to 26 months and it showed that the cross-finger flaps all
      survived with full digital fingertip, satisfactory appearance, good function, and
      normal sense. The discrimination of two points was 5-8 mm. CONCLUSION: As it is
      easy to operate and with satisfactory appearance and good function restoration,
      cross-finger flap with cutaneous branch of the ulnar digital finger is effective
      in repairing the palmar soft tissue defect of the finger.

PMID- 16457445
TI  - [Different types of tissue transplantation in repairing tissue defects and
      function reconstruction].
AB  - OBJECTIVE: To explore the clinical effect of different types of free tissue
      transplantation on repairing tissue defects and reconstructing functions.
      METHODS: From November 2001 to September 2004, 14 types of free tissue
      transplantation and 78 free tissue flaps were applied to repairing tissue defects
      and reconstructing functions in extremities and maxillofacial region in 69 cases.
      Of the 69 cases, there were 53 males and 16 females (their ages ranged from 18 to
      56, 31 on average). Five cases were repaired because of skin defects in foot, 22
      cases were repaired because of skin defects in leg, 36 cases were repaired as the
      result of skin defects in hand or forearm and finger reconstruction, 3 cases were
      restored by virtue of ulna or radius defects, and 3 cases were repaired in
      maxillofacial region. There were 55 cases of open wound, in which 16 cases were
      infectious wound, 6 cases were osteomyelitis or pyogenic arthritis. There were 14
      cases of non-infectious wound. The area of these tissue flaps ranged from 2.0 cm
      x 1.5 cm to 43.0 cm x 12.0 cm. The length of bone transplantation ranged from 10
      cm to 15 cm. RESULTS: Arterial crisis occurred in 2 cases, venous crisis occurred
      in 2 cases. Seventy-six flaps survived completely and 2 flaps survived partially
      which were later healed. Fifty-two cases were healed at stage I, 13 cases were
      healed at stage I (healing time ranged from 20 to 30 days), purulent infection
      occurred to 4 cases(healing time ranged from 3 to 11 months). Bone healing time
      ranged from 6 to 8 weeks in finger reconstruction. Bone healing time ranged from
      4 to 6 months in fibula transplantation. The function reconstruction and
      appearance were satisfying. The functions of all regions, where free tissues were
      supplied, were not disturbed. CONCLUSION: Tissue transplantation and composite
      tissue transplantation are effective in repairing tissue defects and
      reconstructing functions.

PMID- 16457446
TI  - [Anatomical study on restoration of the sensation of distal based sural island
      flap].
AB  - OBJECTIVE: To investigate the anatomic foundation of using main branch of
      posterior femoral nerve to restore the sensation function of distal based sural
      island flap. METHODS: Thirty cases of adult human cadaver legs fixed by 4%
      formaldehyde were used. Anatomical investigation of the posterior femoral nerves
      of lower legs was conducted under surgical microscope to observe their
      distribution, branches and their relationship with small saphenous vein. Nerve
      branches with diameter more than 0.1 mm were dissected and accounted during
      observation. The length and diameter of the nerves were measured. RESULTS: The
      main branch of posterior femoral nerve ran downwards from popliteal fossa within
      superficial fascia along with small saphenous vein. 70% of the main branch of the
      posterior femoral nerves lay medially to small saphenous vein, and 30% laterally.
      They were classified into 3 types according to their distribution in lower legs:
      type I (33.3%) innervated the upper 1/4 region of lower leg (region I), type II
      (43.3%) had branches in upper 1/2 region (region I and II), and type III (23.3%)
      distributed over the upper 3/4 region (region I , II and III). In type II, the
      diameter of the main branches of posterior femoral nerves in the middle of
      popliteal tossa was 1.0 +/- 0.4 mm and innervated the posterior upper-middle
      region (which was the ordinrary donor region of distal based sural island flaps)
      of lower legs with 2.0 +/- 0.8 branches, whose diameter was 0.3 +/- 0.2 mm and
      length was 3.5 +/- 2.7 mm. The distance between the end of these branches and
      small saphenous vein was 0.8 +/- 0.6 mm. In type III, their diameter was 1.2 +/-
      0.3 mm and innervated the posterior upper-middle region of lower legs with 3.7 +/
      1.7 branches, whose diameter was 0.4 +/- 0.1 mm and length was 3.7 +/- 2.6 mm.
      The distance between the end of these branches and small saphenous vein was 0.8
      +/- 0.4 mm. CONCLUSION: 66.6% of human main branch of posterior femoral nerves
      (type II and type III) can be used to restore the sensation of distal based sural
      island flap through anastomosis with sensor nerve stump of foot during operation.

PMID- 16457447
TI  - [The effect of transferring adjacent non-main vessel pedicle flap on repairing
      the heel].
AB  - OBJECTIVE: To explore the effect of transferring adjacent non-main vessel pedicle
      flap on repairing the heel skin defect. METHODS: From February 2000 to April
      2004, 4 kinds of flaps with non-main vessel pedicle were used to repair 30 cases
      of heel skin defect. Of the 30 patients, 19 were male and 11 were female, whose
      ages ranged from 8 to 65. Among them, 19 cases were crush injury, 5 cases were
      press injury, 3 cases were electric saw injury, 2 cases were osteomyelitis, and 1
      case was squamous cell carcinoma. Fourteen cases were with defect area ranged
      from 6.0 cm x 5.5 cm to 16.5 cm x 11.0 cm. All the 14 cases were repaired with
      distant pedicled sural vascular flap of nutrient vessels and saphenous vascular
      flap of nutrient vessels. The sizes of the dissected flap ranged from 6.0 cm x
      5.0 cm to 18.0 cm x 12.0 cm. And the other 16 cases with defect area ranged from
      2.5 cm x 2.0 cm to 5.5 cm x 4.5 cm were repaired with foot lateral flap and foot
      base medial flap. The sizes of the dissected flap ranged from 4.0 cm x 3.0 cm to
      8.0 cm x 7.0 cm. RESULTS: All cases were followed up for 6 to 12 months. The
      flaps all survived with satisfactory appearance and no ulceration. Callus
      appeared in 2 cases. The sense of pain and touch was partly or completely
      restored. The two-point discrimination sense recovered to 1.0-3.2 cm. CONCLUSION:
      As it is easily accessible, highly flexible and causes little damage to blood
      circulation, transferring adjacent non-main vessel pedicle flap, is effective in
      repairing foot heel skin defect.

PMID- 16457448
TI  - [The effect of micro-trauma technic with small incision on treating hallux
      valgus].
AB  - OBJECTIVE: To explore an effective micro-trauma technic with small incision for
      hallux valgus. METHODS: From August 2002 to June 2004, 136 cases (263 feet) with
      hallux valgus were treated with micro-trauma technic with small incision and
      postoperative external elastic fixation. Of all the cases, 7 were males and 129
      were females. Their ages ranged from 19 to 84 years. According to Coughlin
      classification, there were 24 gentle cases, 63 medium cases, and 49 severe cases.
      All the feet were with some degree of pain and flatfoot. Symptom, sign and the
      results of X-ray were evaluated. RESULTS: Wound healed at stage I. All cases were
      followed up for 8 to 26 months, 19 months on average. Hallux valgus of the 263
      feet were completely healed, feet pain disappeared, and no nonunion or
      osteonecrosis was observed. X-ray examination indicated that 105 feet's hallux
      valgus angle was less than 12 degrees, inter metatarsal angle less than 9
      degrees, and remedy subluxation of the tibial sesamoid less than 50%. Evaluation
      on the result indicated that there were 84 cases of excellent result, 48 cases of
      good result, 3 cases of fair result, and 1 case of poor result. The rate of
      excellent and good was 97%. CONCLUSION: With less injury, less pain, complete
      restoration, and fewer possibility of relapse, micro-trauma technic with small
      incision is effective in treating hallux valgus.

PMID- 16457449
TI  - [Study on the differentiation of marrow mesenchymal stem cells of the rats
      mediated by bone morphogenetic protein 2].
AB  - OBJECTIVE: To explore the effect of age and gene therapy on the differentiation
      of marrow mesenchymal stem cells (MSCs) of the rats. METHODS: MSCs from the young
      (1-month-old), adult (9-month-old), and the aged (24-month-old) rats were
      expanded in culture and infected with adenovirus mediated human bone
      morphogenetic protein 2 gene (Ad-BMP-2). The expression of BMP-2 and osteoblastic
      markers such as alkaline phosphatase (ALP), collagen I (Col I), bone sialoprotein
      (BSP) and osteopontin (OPN) were assayed during the process of differentiation.
      Their abilities to induce ectopic bone formation in nude mice were also tested.
      RESULTS: There was no significant difference in the expression of BMP-2 among the
      3 groups. ALP activity assay and semi-quantitative reverse transcription
      polymerase chain reaction(RT-PCR) demonstrated that there were no significant
      differences in the expression of osteoblastic markers ALP, Col- I, OPN and BSP
      among the 3 groups. Histomorphometric analysis indicated that there were no
      significant differences in the volume of the newly formed ectopic bones in nude
      mice among the 3 groups. CONCLUSION: MSCs obtained from the aged rats can restore
      their osteogenic activity following human BMP-2 gene transduction,therefore
      provides an alternative to treating the aged bone disease.

PMID- 16457450
TI  - [A model for studying on mechanical responses of osteoblast seeded in three
      dimensional scaffold].
AB  - OBJECTIVE: To establish a model for studying on mechanical responses of
      osteoblasts seeded in 3 dimensional(3D) scaffold. METHODS: Fifty pieces of bio
      derived cancellous bones, whose holes were 500 to 800 microm and density was 0.36
      to 0.45 g/cm3, were obtained as the scaffolds. They were cultured with the third
      passage suspension of Wistar rat. Twenty-four of the 50 scaffolds were
      constructed under apparent strain sine waveform with amplitude of 1 000
      microepsilon, frequency of 3 Hz, and duration of 3 min/d, as experimental group.
      The other scaffolds were control group. After 3-day coculture, osteoblasts were
      observed with scanning electron microscope. The proliferation of the osteoblasts
      was checked by MTT on scheduled date. RESULTS: Scanning electron microscopic
      observation showed that osteoblasts attached and spread on the trabeculae, which
      presented the validity of the model under proper mechanical condition. Experiment
      showed that mechanical environment promoted the proliferation of osteoblasts. The
      observation of proliferation of osteoblasts showed that the quantity of
      osteoblasts in the experimental group was higher than that in the control group
      1, 4, 8, 12, 16, 20, 24, and 28 days after culturing. There was significant
      difference between the two groups 12, 16, 20, 24, and 28 days after culturing (P
      < 0.05). CONCLUSION: The establishment of the model can facilitate the study of
      mechanical responses of osteoblasts under different conditions.

PMID- 16457451
TI  - [The extracellular matrix in bone tissue engineering].
AB  - OBJECTIVE: To review the research progress of osteoblast extracellular matrix
      (ECM) and its application in bone tissue engineering. METHODS: The recent related
      literatures were extensively reviewed. RESULTS: The ECM was complex in its
      components. The configuration of cell and cell's adhesion, migration,
      proliferation, and differentiation were subject to the ECM. The bioactivity of
      the tissue engineering products was revealed by ECM, which predicted the
      product's efficiency in clinic application. CONCLUSION: ECM has the potential to
      become the effective index in evaluating tissue engineered products.

PMID- 16457452
TI  - [Basic study on the development of amniotic membrane and its application].
AB  - OBJECTIVE: To review the latest development of amniotic membrane and its
      application. METHODS: Related literatures on the development of amniotic membrane
      and its application were extensively reviewed and summarized. RESULTS: There were
      amniotic epithelial cells and many growth factors in the outer layer of amniotic
      membrane and there were many kinds of collagen in the basement. The special
      structure promoted the growth of many kinds of cells. It was widely used in
      ophthalmology. CONCLUSION: As it is easily available, compatible, cheap in price,
      low in antigenicity, and able to promote the growth of many kinds of cells, with
      few ethical problems involved, amniotic membrane will be more and more widely
      applied.

PMID- 16457453
TI  - [An experimental study on transplantation of frozen canine phalangeal joint
      allografts incorporated with autogenic bone marrow].
AB  - OBJECTIVE: To investigate the result of the transplantation of frozen canine
      phalangeal joint allografts perforated and incorporated with autogenic bone
      marrow. METHODS: A proximal interphalangeal joint defect of 1.5 cm was prepared
      at bilateral sides of twenty-four adult healthy out-bred dogs. Three different
      types of allografts were applied to repair the defects: fresh autogenic
      phalangeal joints (group A, n = 16), frozen phalangeal joint allografts
      perforated and incorporated with fresh autogenic bone marrow (group B, n = 16),
      and frozen phalangeal joint allografts (group C, n = 16). Radiographic and
      histological study were used to evaluate the survival of transplanted joints. The
      observation was done 1, 3, 6 and 12 months after operation respectively. RESULTS:
      Based on the radiographic and histological changes of the transplanted joints,
      the osteoarthropathy of transplanted canine phalangeal joints could be divided
      into 3 degrees: mild degeneration, moderate degeneration and severe degeneration.
      Mild degeneration was observed in group A from 3 to 12 months. Mild degeneration
      was also found in group B from 1 to 6 months, and the endochondral ossification
      was obvious within the drilled bony holes. However, some joints in group B
      underwent moderate degeneration 12 months after operation. Group C joints in the
      first month had moderate degeneration, which progressed to severe degeneration 3
      months after operation. CONCLUSION: Transplantation of frozen canine phalangeal
      joint allografts perforated and incorporated with autogenic bone marrow can
      effectively delay the degeneration of transplanted osteoarticular allografts at
      the early and middle stage.

PMID- 16457454
TI  - [Experimental study on the tracheal allografts with decreased antigenicity].
AB  - OBJECTIVE: To investigate effect of the removal of epithelium and mixed glands
      from the tracheal allografts on the graft-immunosuppression. METHODS: Fresh
      untreated tracheal allografts, cryopreserved tracheal allografts, and 10 off
      epithelium tracheal allografts were obtained from 25 male SD rats. Fresh
      untreated tracheal allografts (40) were divided into 4 groups and dipped
      respectively in the solution of protease XIV in 0, 0. 1, 0.3 and 0.5 mg/ml at 4 C
      for 12 hours. Thirty recipient male SD rats were randomly and equally divided
      into group A (fresh untreated tracheal allografts), group B (cryopreserved
      tracheal allografts), and group C (off-epithelium tracheal allografts). The
      transplanted allografts were implanted into the abdominal cavity of other rats by
      being embedded in the greater omentum. Twenty-one days after transplantation, the
      tracheal graft segments were surgically removed, and then were initially fixed in
      cold 10% neutral buffered formalin solution for hematoxylineosin staining.
      Histological observation and lymphocyte infiltration were performed on the grafts
      to evaluate rejection. RESULTS: The 0.3 mg/ml protease XIV could remove the
      epithelium and mixed glands of the grafts completely, but did no damage to
      cartilage. The cartilages of each group all survived and were revascularized. The
      lumens of group A were filled with granulation and necrosis tissue. In contrast,
      group B was filled with a few granulation tissues and group C was not at all. The
      number of lymphocyte infiltration in group A, B, and C was 29.16 +/- 2.69/HP,
      15.17 +/- 2.19/HP, and 11.56 +/- 0.87/HP respectively. There was significant
      difference between group A and both group B and group C (P < 0.05), and there was
      significant difference between group B and group C (P < 0.05). Therefore, the
      grade of graft-rejection was group A > group B > group C. CONCLUSION: The 0.3
      mg/ml protease XIV can completely remove the epithelium and mixed glands of
      grafts at 4 C for 12 hours, and it preserves the normal structure of cartilage.
      The antigenicity of tracheal grafts can be greatly reduced by removing the
      epithelium and by the cryopreservation. The prior tracheal allograft in the
      omentum is feasible for the revascularization of the grafts.

PMID- 16457455
TI  - [Study on the application of allogeneic bone transplantation].
AB  - OBJECTIVE: To explore the clinical application of allogeneic bone
      transplantation. METHODS: Related literatures on clinical application of various
      allograft bone materials of the past 5 years were extensively reviewed. RESULTS:
      The allografts could be processed into various kinds of transplanting materials,
      such as small blocks, large segments, morselized or granular material, and bone
      ring, so that they could be applied to bone defect filling, prosthesis revision,
      limb preservation after tumor resection, and joint fusion. All these applications
      ended up with good clinical results. However, complications resulted in the
      structural transplantation of large block bones could be overlooked. CONCLUSION:
      The main advantage of bone allograft is that it can be integrated with host bone
      and be remodelled, so as to reconstruct bone structure and function. How to
      accelerate functions is the problem that requires solution. their integration and
      remodelling while exerting normal functions is the problem that requires
      solution.

PMID- 16457456
TI  - [Study on the research progress of artificial osteoconductive materials].
AB  - OBJECTIVE: To review the recent research and clinical progress of artificial
      osteoconductive materials. METHODS: Recent and related literatures were
      extensively and comprehensively reviewed. RESULTS: Many achievements about the
      clinical application of the artificial osteoconductive materials were made. It
      had become one of the hotspots of bone tissue engineering research. Some were
      clinically applied and good clinical results were achieved. CONCLUSION: As it
      provides new clinic method for treating bone defect, artificial osteoconductive
      material is of great potential in its application. To improve its microstructure,
      macro-shape, mechanism of osteoinductive ability, and to accelerate new bone
      formation will be the hotspots of the research on artificial osteoconductive
      material.

PMID- 16457457
TI  - Rekindling the fire of family medicine.

PMID- 16457458
TI  - Homogenized lemmings, continued.

PMID- 16457459
TI  - EHRs and disaster management.

PMID- 16457460
TI  - Improving chronic care.

PMID- 16457461
TI  - CPT 2006: Another year, another round of updates.

PMID- 16457462
TI  - Preparing for an influenza pandemic: vaccine prioritization.

PMID- 16457463
TI  - Group visits for chronic illness care: models, benefits and challenges.

PMID- 16457464
TI  - 7 characteristics of successful work relationships.

PMID- 16457465
TI  - Are you ready for Medicare Part D?

PMID- 16457466
TI  - The firing squad.

PMID- 16457467
TI  - Microbiological risk factors in dentistry. Current status of knowledge.
AB  - Dentists belong to a professional group potentially exposed to harmful biological
      factors which most often are infectious microorganisms, less frequently -
      allergenic or toxic microorganisms. The fundamental routes of spreading harmful
      microorganisms in a dental surgery are: blood-borne, saliva-droplet, direct
      contact with a patient and with infected equipment, and water-droplet infections.
      In this paper, the current status of knowledge on microbiological hazards in a
      dentist's work is presented. Groups of microorganisms, such as prions, viruses,
      bacteria, fungi and protozoa, to which a dentist is, or may be exposed, are
      discussed. Epidemiological assessment of microbiological hazards in a dentist's
      work was performed and the basic principles of prevention formulated. Special
      attention was given to microflora in dental unit waterlines, and the biofilm
      persisting in them, as a source of occupational hazards specific for a dentist's
      workplace.

PMID- 16457468
TI  - Association of genetic variability within the Borrelia burgdorferi sensu lato
      with the ecology, epidemiology of Lyme borreliosis in Europe.
AB  - Lyme borreliosis (LB) represents the most common vector-borne zoonotic disease in
      the Northern Hemisphere. The infection is caused by the spirochetes of the
      Borrelia burgdorferi sensu lato (s.l.) complex which circulate between tick
      vectors and vertebrate reservoir hosts. The complex of Borrelia burgdorferi s.l.
      encompasses at least 12 species. Genetic variability within and between each
      species has a considerable impact on pathogenicity, clinical picture, diagnostic
      methods, transmission mechanisms and its ecology. The distribution of distinct
      genospecies varies with the different geographic area and over a time. In recent
      years, new molecular assays have been developed for direct detection and
      classification of different Borrelia strains. Profound studies of strain
      heterogeneity initiated a new approach to vaccine development and routine
      diagnosis of Lyme borreliosis in Europe. Although great progress has been made in
      characterization of the organism, the present knowledge of ecology and
      epidemiology of B. burgdorferi s.l. is still incomplete. Further information on
      the distribution of different Borrelia species and subspecies in their natural
      reservoir hosts and vectors is needed.

PMID- 16457469
TI  - Nasal provocative test in patients allergic to pollen.
AB  - Nasal provocative test (NPT) can be defined as a method for recreating upper
      respiratory tract response to natural allergens or irritants. It can be used in
      solving nasal patophisiology problems: establishing whether and how the patient's
      nose is sensitive to antigens or irritants; quantitative evaluation of
      sensitivity; establishing factors influencing sensitivity. This method is
      employed to confirm clinical diagnosis in cases where difficulties arise in
      interpretation of diagnostic tests. The study based on nasal provocative tests
      establish an allergy to pollen in cases of pollinosis, and select appropriate
      components for the desensitising vaccine. Sample group included 53 patients, 29
      were females and 24 were males, aged 15-42 years, selected from 1,021 patients
      diagnosed between 1999-2002 in the Allergology Department of the ENT Department
      of the MMI. The sample patients were diagnosed based on additional tests with
      allergic inflammation of the nasal mucosa caused by allergy to pollen of such
      plants as birch, grass, rye, mugwort and plantain. Research methods included:
      subjective physical examination, prick tests, total and specific IgE levels in
      serum, nasal provocative tests and rhinomanometric examination. Allergen solution
      was administered onto the mucosa with a calibrated atomiser. NPT solutions
      containing pollen of birch, grass, rye, mugwort and plantain were used.
      Provocative test was considered positive if, following allergen provocation,
      rhinomanometric examination revealed an increase in respiratory resistance by at
      least 40 % in comparison with the control test. On the basis of the study, 2
      conclusions were drawn: 1) Nasal provocative test is an essential element in
      diagnostics of allergic nasal obstruction. 2) Rhinomanometry, as an objective
      method of examining nasal patency, is crucial for evaluating the nasal
      provocative test.

PMID- 16457470
TI  - Effect of pesticides on kynurenic acid production in rat brain slices.
AB  - Kynurenic acid (KYNA) is a broad spectrum antagonist of ionotropic glutamate
      receptors, preferentially active at the strychnine-insensitive glycine allosteric
      site of the N-methyl-D-aspartate (NMDA) receptor, and a noncompetitive antagonist
      of alpha7 nicotinic receptor. Animal studies showed that it possesses
      anticonvulsant and neuroprotective properties. Its involvement in the
      pathophysiology of various brain disorders was suggested. In this study, the
      effect of pesticides on KYNA production in brain cortical slices was
      investigated. Pyrethroids, deltamethrin and fenpropathrin significantly lowered
      KYNA production. Methomyl, bensultap, fipronil, diquat and MCPA were ineffective
      in this regard. In view of this data, the inhibition of KYNA synthesis appear to
      merit further investigation as a potential factor contributing to the toxicology
      of pyrethroids.

PMID- 16457472
TI  - Bacterial contamination of indoor air, surfaces, and settled dust, and related
      dust endotoxin concentrations in healthy office buildings.
AB  - Endotoxin, a characteristic external fraction of the outer membrane from Gram
      negative bacteria, continuously shed into the environment, is considered as an
      important risk factor for human health. Our purpose was to study the bacterial
      species contaminating healthy working environments. Airborne, working surfaces
      and carpet dust samples were collected from 25 offices. Bacterial species were
      identified with biochemical ApiSystem strips. Endotoxin concentrations in settled
      dust were measured with the kinetic chromogenic Limulus assay. The airborne
      bacterial level varied from 44-2,511, with a median of 277 cfu/m(3). Bacterial
      contamination on surfaces ranged from 1-1000, with 33 cfu/25 cm(2) as median
      value. On carpets, bacterial concentration ranged from 0.73-185 x 10(5) cfu/g,
      with 7.28 x 10(5) cfu/g as median value. Endotoxin concentration varied from 4.6
      116.2 EU/mg, with a median of 20.3 EU/mg. Altogether, 501 bacterial strains were
      isolated. The species variability was greater in Gram-negative bacteria than in
      Gram-positive cocci with 41 versus 34 various species. In conclusion, people
      working in healthy offices can be exposed to large concentrations of airborne and
      dust bacteria and related endotoxin concentrations, giving a risk of work-related
      diseases.

PMID- 16457471
TI  - Lymphatic filariasis among the Ezza people of Ebonyi State, eastern Nigeria.
AB  - A total of 1,243 Ezza people living in 10 communities of Ebonyi State, eastern
      Nigeria were examined between July 2002-January 2003 for lymphatic filariasis.
      This is the first time a filariasis survey due to Wuchereria bancrofti has been
      carried out in this state. Of the 1,243 persons examined, 210 (16.9 %) had W.
      bancrofti microfilariae. Infection varied significantly among communities and
      ages (p < 0.05) but not sex-related (p > 0.05). The Ezza people are predominantly
      farmers and professional hired labourers. There was a close association between
      microfilaria rate and microfilaria -density in various age groups (r = 0.812; p <
      0.01). Microfilaria density is an important measure in the epidemiology,
      treatment and control of human filarisis in this endemic foci. Clinical signs and
      symptoms of the disease include elephantiasis, hydrocoele, dermatitis and
      periodic fever. Clinical symptoms without microfilaraemia and microfilaraemia
      without clinical symptoms were also observed. Of 1,603 mosquitoes dissected,
      Anopheles gambiae, An. funestus and Culex quinquefasciatus showed infectivity
      rates of 6.3 %, 5.1 % and 6.0 % respectively. The affected persons and other key
      informants are unaware of the cause of the disease and attributed it to
      witchcraft, violation of taboo, bad water and food. Intervention strategies to be
      integrated into the on-going Community-Directed Treatment with Ivermectin (CDTI)
      project are discussed.

PMID- 16457473
TI  - Aflatoxin and ochratoxin in various types of commonly consumed retail ground
      samples in Ankara, Turkey.
AB  - To detect aflatoxin (AF) or ochratoxin A (OTA) contamination, 25 retail ground
      samples of 12 different types of seed-, pulses-, and cereal-flours and starches
      were randomly collected from markets and traditional bazaars in Ankara, Turkey.
      The levels of AF in the retail ground samples were determined by high performance
      liquid chromatography (HPLC) and ranged from 0.03-3.16 ppb. The percentage of
      contaminated samples for aflatoxin B(1), B(2), G(1), and G(2) were 64, 60, 72,
      and 76 %, respectively. The determination of OTA level was performed by enzyme
      linked immunosorbent assay (ELISA), and they were ranged between 0.27-4.07 ppb
      (n=24). However, the screened mycotoxin levels in the samples were under the
      permission limits of Turkey, the daily intake of these products corresponds to at
      least 50 % of daily diet in our country. Routine measurements of the toxin levels
      in foods and feeds should be carried out to prevent their harmful effects on
      health.

PMID- 16457474
TI  - Prevalence of DNA and antibodies to Borrelia burgdorferi sensu lato in dogs
      suspected of borreliosis.
AB  - The aim of the paper was an attempt to correlate clinical signs with the presence
      of DNA of Borrelia burgdorferi (sensu lato) s.l. and the antibodies against B.
      burgdorferi s.l. in the blood of dogs. Among the animals studied there were 62
      dogs delivered to the Veterinary Clinic in Szczecin and 30 from the Municipal
      Animal Shelter in Szczecin with varied clinical signs of borreliosis. In all
      cases the owners admitted frequent contacts of their dogs with ticks, both in the
      past, as well as shortly before the onset of sickness. We used two methods: PCR
      for detecting DNA of B. burgdorferi s.l. and ELISA test for detecting antibodies
      against the spirochete. Lameness, the principal symptom of canine borreliosis was
      the most frequent symptom of the group of 31 PCR-positive animals. The other most
      common symptoms in PCR-positive dogs were fever, swelling of joints and loss of
      body weight. DNA of B. burgdorferi s.l. was most frequently detected in the blood
      of dogs of the group 2-5 years old (13/54.1 %). ELISA tests specific for IgG
      antibodies were positive in 37 of 92 sera (40.2 %) taken from examined dogs.
      Lameness was observed in 15 of 37 IgG-seropositive dogs and in 25 of 55
      seronegative animals. In 54 % of dogs with the antibodies, swelling of instep-
      and wrist joints was observed compared to only 24.4 % in seronegative dogs. An
      attempt to correlate the PCR results with the results of tests detecting
      antibodies against B. burgdorferi s.l. revealed that fewer than half (45.1 %) of
      the dogs with presence of DNA of the spirochete, developed an immune response.
      Therefore the transfer of B. burgdorferi s.l. form, the primary lesion to the
      target tissues, is possible in dogs which did not develop immune response or
      develop an insufficient response. Among 92 borreliosis-suspected dogs 54 (over 58
      %) were diagnosed positively using laboratory methods. In most cases there was a
      correlation between clinical symptoms of borreliosis and presence of DNA B.
      burgdorferi, thus PCR may contribute to improving to a large extent diagnostic of
      canine Lyme disease.

PMID- 16457475
TI  - Function of heart muscle in people chronically exposed to lead.
AB  - Rhythm and conductivity disturbances in heart muscle, change in autonomic system
      function and raised arterial blood pressure have been described in workers
      exposed to lead. They may be accompanied by changes in echocardiography test and
      accordingly we undertook this investigation. The study population included
      employees of zinc and lead steelworks in the south of Poland that were divided
      into 2 groups: exposed to lead compounds (n=88) and the reference group -
      administration workers (n=55) with normal levels of lead concentration in blood
      (PbB) and zinc protoporphyrin in blood. Left ventricular enddiastolic dimension
      (LVDd), interventricular septal and posterior wall thickness, right ventricular
      diastolic, left atrium diameter, aortic diameter and left ventricular ejection
      fraction (EF) in echocardiograms were performed. Left ventricular mass LVM (g)
      and left ventricular mass index LVMI (g/m(2)) was calculated. In the group
      exposed to lead, EF decreased by 3 %, increased LVDd by 6 %, and raised LVM by 11
      % and LVMI by 10 %. There was a positive relation between PbB and LVDd (R=0.18)
      and between PbB and LVM (R=0.14). Decreased EF, enlargement of the left ventricle
      and raised left ventricle mass in research undertaken, may be a result of raised
      arterial blood tension.

PMID- 16457476
TI  - Evaluation of salting as a hay preservative against farmer's lung disease agents.
AB  - Salting is a traditional, empirical practice used commonly in dairy farming
      regions to prevent moulding and heating in hay. Our aim was to evaluate the
      effect of salting hay on the proliferation of microorganisms, particularly
      thermophilic actinomycetes and moulds involved in farmer's lung disease. Fifty
      one pairs of salted and unsalted hay bales from 14 farms were produced during the
      haymaking season between March and July. Both the salted and the unsalted bales
      came from the same field, and were packed and stored under identical conditions.
      Sampling was performed by microbiological analysis including 6 culture media
      during the winter following salting (January-February). The use of salt did not
      significantly decrease the amount of Saccharopolyspora rectivirgula , the
      actinomycetes most commonly involved in farmer's lung disease, or that of Absidia
      corymbifera, Eurotium amstelodami and Wallemia sebi , three moulds responsible
      for farmer's lung disease in eastern France. Our results are important in that
      they can inform farmers and dispel the false sense of security induced by
      salting, which is reinforced by the misconception that palatable hay is healthy
      hay.

PMID- 16457477
TI  - Obtaining health information from farmers: interviews versus postal
      questionnaires in a New Zealand case study.
AB  - PURPOSE: To compare the effectiveness of interviewer-led and postal surveys in
      gathering adequate health data for occupational health programmes among farmers.
      METHODS: Two cross-sectional studies of farmers from southern New Zealand were
      conducted. Farms were randomly selected from the public land valuation roll and
      all farmers and farm workers invited to participate in the farmers' health study.
      First, 477 farms were invited to participate in an interviewer administered
      questionnaire and health check; and second, a further 432 farms were selected and
      invited to participate in a self-administered postal survey. Both groups
      completed the same questionnaire. RESULTS: The response for the interviewer-led
      and postal surveys was 65.4 % and 51.6 % respectively. The 2 groups differed
      demographically, with fewer young farm workers in the postal survey, but were
      similar in all areas of health information collected, except that men in the
      interviewer-led survey were significantly more likely to have a psychological
      disturbance than men in the postal survey (chi ( 2 ) =5.06, df=1, p=0.024).
      CONCLUSIONS: Despite the interviewer-led survey having a higher response rate,
      the postal survey produced similar health data, which is adequate for planning
      occupational health programmes for farmers. Extra effort should be made to
      recruit younger farm workers in future research.

PMID- 16457478
TI  - Endotoxin level as a potential marker of concentration of Gram-negative bacteria
      in water effluent from dental units and in dental aerosols.
AB  - Gram-negative bacteria concentration in water effluent from a dental unit, and in
      dental aerosol forming during the work of a dental handpiece, was assessed. The
      study was conducted on 25 dental units before and after a 2-week period of using
      a disinfecntant for water in dental units waterlines (DUWL). The contamination of
      water with Gram-negative bacteria before disinfection was 18-398 x 10(3) cfu/ml,
      and after disinfection, bacteria were not found. The concentration of Gram
      negative bacteria in the air before disinfection was 0-23 x 10(1) cfu/m(3), and
      after disinfection - 0-8 x 10(1) cfu/m(3). Simultaneously, the water and air were
      sampled to determine bacterial endotoxin. The statistical analysis did not show
      correlation between endotoxin concentration and Gram-negative bacteria
      concentration for the water before disinfection, and for the air before and after
      disinfection of DUWL water. Because the number of bacteria in the water after
      disinfection dropped to zero, statistical methods could not be used. The
      performed analysis suggests that bacterial endotoxin concentration is not
      indicative of Gram-negative bacteria contamination. Thus, bacterial endotoxin
      determination is not recommended as a method of monitoring the microbiological
      quality of DUWL water and dental aerosols.

PMID- 16457479
TI  - Evaluation of Acanthamoeba isolates from environmental sources in Tenerife,
      Canary Islands, Spain.
AB  - Tests for potentially pathogenic amoebae were carried out in order to determine
      the presence of free-living amoebae of genus Acanthamoeba in soil and beach sand
      sources related to human environments in Tenerife, Canary Islands, Spain.
      Acanthamoeba identification was based on the morphology of cyst and trophozoite
      forms and PCR amplification with a genus specific primer pair. The pathogenical
      potential of Acanthamoeba isolates was characterized by temperature and
      osmotolerance assays and PCR reactions with two primer pairs related to
      Acanthamoeba pathogenesis. The results demonstrate the presence of potential
      pathogenic strain in both sources. Thus, some of the amoebae found in these
      habitats could act as opportunistic pathogens and may present a risk to human
      health.

PMID- 16457480
TI  - Intestinal macro- and microparasites of wolves (Canis lupus L.) from north
      eastern Poland recovered by coprological study.
AB  - Wolf scats collected during ecological studies in Mazury lake district in NE
      Poland were analysed for intestinal micro- and macroparasites. Five nematode
      species were identified: Ancylostoma caninum (Ercolani, 1859), Uncinaria
      stenocephala (Railliet, 1884), Trichuris vulpis (Froelich, 1789), Toxocara canis
      (Werner, 1782) and Toxascaris leonina (von Linstow, 1902). Among cestode species
      there were identified infections with Dipylidium caninum (Linnaeus, 1785). The
      overall helminth prevalence was 63.5 % and average intensity was 15.4 +/- 8.0
      eggs /1g of sample. The most prevalent parasite was T. vulpis (38.5 %) and the
      most abundant infections were by T. canis. Almost 55 % of samples (28/51) were
      positive for C. parvum oocysts and 46.7 % (14/30) for Giardia spp. cysts. The
      pack factor affected the distribution of some of macro- and microparasites. The
      identified parasite fauna of wolves in Mazury lake district consists of several
      micro- and macroparasites of interest for public health.

PMID- 16457482
TI  - Micromycetes, producers of toxins, detected on stored vegetables.
AB  - In 2003-2004, investigations of mycological contamination of stored and newly
      harvested vegetables were carried out. The aim of the study was to detect fungal
      species able to synthesize toxic metabolites, which are spread on vegetables
      under various conditions. For mycological investigations, samples of carrots,
      onions and cabbage were taken from storehouses with different storage periods and
      conditions. Penicillium expansum, P. nalgiovense, Mucor silvaticus and
      Penicillium verrucosum were more frequently detected on carrots, Penicillium
      expansum - on onions and Aspergillus niger, Botrytis cinerea, Mucor hiemalis,
      Penicillium funiculosum and Penicillium expansum - on cabbages. Storing
      conditions of vegetables influenced distribution of different fungal species.
      Primary screening using CYA and YES test-media showed that 46.7 % of tested
      strains may be evaluated as toxin producers. The ability of fungi to produce
      mycotoxins depends on their growth substrata. According to Rf and fluorescence in
      the UV of compounds comparing with standards, such toxins as patulin,
      cytochalasin and penitrem were identified. The ability of Penicillium expansum Sv
      168-1 growing on different foodstuff and especially potato to produce patulin was
      confirmed quantitatively.

PMID- 16457481
TI  - Health effects of exposure to herb dust in valerian growing farmers.
AB  - The aim of the present study was to determine the health status of farmers
      cultivating valerian (Valeriana officinalis L.) and occupationally exposed to
      dust from this plant. A group of 75 valerian growing farmers were examined. As a
      reference group, 50 urban dwellers, not exposed to any kind of organic dust were
      examined. All people were interviewed for the presence of work-related symptoms
      and subjected to physical and spirometric examinations. Skin prick tests were
      conducted with 4 microbial antigens associated with organic dust and 3 herbal
      extracts, precipitin tests with 12 microbial antigens and 4 herbal extracts and
      tests for specific inhibition of leukocyte migration with 4 microbial antigens.
      30.7 % of the valerian farmers reported occurrence of work-related symptoms. No
      significant differences were found between the spirometric values in the group of
      valerian farmers and the reference group. Valerian farmers showed a low frequency
      of positive skin reactions to all tested antigens (0-4.0 %), not significantly
      greater compared to reference group. The frequency of positive precipitin
      reactions to the antigen of Gram-negative bacterium Pantoea agglomerans was very
      high in valerian farmers (45.5 %) with 3-fold concentrated sera and significantly
      greater compared to the reference group (p < 0.001). The positive precipitin
      response of valerian farmers to other microbial and herbal antigens was much
      lower or absent and did not show any difference compared to reference group. In
      the test for specific inhibition of leukocyte migration, the highest frequencies
      of positive reactions in valerian farmers were noted with Pantoea agglomerans and
      Saccharopolyspora rectivirgula (15.0 % each), in both cases significantly greater
      compared to reference group (p < 0.05). In conclusion, the farmers growing
      valerian showed a moderate frequency of work-related symptoms and low reactivity
      to most microbial and herbal allergens. They exhibited an increased immunologic
      response to Gram-negative bacterium Pantoea agglomerans which appears to be the
      most important risk factor associated with valerian dust.

PMID- 16457483
TI  - Low back pain comorbidity among male farmers and rural referents: a population
      based study.
AB  - Farmers report more low back pain (LBP) than rural referents. We have previously
      demonstrated that the difference in reporting rate cannot be fully explained by
      known risk factors such as physical work exposures, psychosocial factors and
      lifestyle. Other etiological factors must be involved. In this cross-sectional
      population-based study, we investigate LBP comorbidity in terms of coexistent
      symptoms. A total of 1,013 male farmers, 40-60 years old, and 769 matched rural
      referents participated in an extensive health survey. Information on causes of
      primary health care and hospital admissions, symptoms, lifestyle factors,
      physical work exposures and psychosocial factors were gathered through
      standardized interviews and questionnaires. In the combined farmer-referent
      group, the prevalence of LBP was associated with musculoskeletal symptoms other
      than LBP, chest discomfort, dyspepsia, symptoms from eyes, nose and throat mucous
      membranes, skin problems, work-related fever attacks, and primary care
      appointments due to digestive disorders. The associations were independent of
      age, educational level, smoking habits, body mass index, physical work exposures
      and psychosocial factors. Presence of both respiratory and digestive disorders
      doubled the LBP prevalence. Significant associations between LBP and digestive
      and respiratory disorders were revealed, indicating that LBP and these disease
      entities may have etiological factors in common.

PMID- 16457484
TI  - Exposure of Indian agricultural workers to airborne microorganisms, dust and
      endotoxin during handling of various plant products.
AB  - Microbiological air sampling with the use of personal sampler was performed in 14
      small agricultural facilities located in Aurangabad (Southern India), including 5
      farms (at harvesting and threshing), 6 godowns (small food storing and processing
      settings) and 3 grain or cotton mills. In 12 facilities, including harvesting on
      farms, godowns and mills, concentrations of airborne microorganisms were
      relatively low, ranging from 1.5 x 10(3) - 8.2 x 10(4) cfu/m(3). The striking
      rise in the concentrations of airborne microbes, by 2-4 orders of magnitude, was
      noted on 2 farms during threshing of maize (4.2 x 10(6) cfu/m(3)) and pearl
      millet (1.1 x 10(7) cfu/m(3)). This was due to release of large quantities of
      bacteria. During threshing of maize, the most common microorganisms were
      thermophilic actinomycetes (40 % of the total count) and mesophilic actinomycetes
      of the genus Streptomyces (39 %), while during threshing of pearl millet the most
      abundant were corynebacteria (68 %) and Gram-negative bacteria (22 %). Mesophilic
      bacteria formed 16.7-100 % of the total airborne microflora and were prevalent in
      11 out of 14 facilities. Thermophilic actinomycetes and fungi formed respectively
      0-43.1 % and 0-83.3 % of the total count and were prevalent in 1 and 2
      facilities. The concentrations of airborne dust and endotoxin recorded in the
      examined agricultural facilities, in most cases were very large and ranged from
      2.5-257.5 mg/m(3), and from 0.0625-125.0 microg/m(3), respectively. In 10 out of
      14 facilities, the concentrations of dust were of the order 10(1)-10(2) mg/m(3),
      ranging from 25.0-257.5 mg/m(3). Similarly, in 7 out of 14 facilities the
      concentrations of endotoxin were of the order 10(1)-10(2) microg/m(3), ranging
      from 31.25-125.0 microg/m(3). In conclusion, Indian agricultural workers could be
      exposed during handling of various plant materials to airborne biological hazards
      posing a risk of work-related respiratory disease. Of these, the most important
      are: bacterial endotoxin and allergenic species of bacteria and fungi. The
      greatest risk occurs at threshing of pearl millet and maize which requests an
      application of the appropriate prevention measures, such as wearing respirators
      by the workers and using modern threshing machines reducing the dustiness.

PMID- 16457485
TI  - Regional differentiation of palm dermatoglyphs in rural population in Poland.
AB  - The study presents a comparison of the distribution of palm dermatoglyphs in the
      rural populations of different regions of Poland, namely, the Lublin region, the
      areas of Suwalki, Ostroleka, and of the village of Gieblo. A comparison of the
      occurrence frequency of dermatoglyphs in the above-mentioned areas reveals
      statistically significant differences between particular patterns. The
      differences result from ethnic isolation and isolation of the communities caused
      by geographical barriers.

PMID- 16457486
TI  - Exposure to airborne microorganisms, dust and endotoxin during processing of
      peppermint and chamomile herbs on farms.
AB  - The aim of this study was to determine the levels of microorganisms, dust and
      endotoxin in the air during processing of peppermint (Mentha piperita) and
      chamomile (Matricaria recutita) by herb farmers, and to examine the species
      composition of airborne microflora. Air samples were collected on glass fibre
      filters by use of personal samplers on 13 farms owned by herb cultivating
      farmers, located in Lublin province (eastern Poland). The concentrations of total
      viable microorganisms (bacteria + fungi) in the farm air during processing of
      peppermint herb were large, within a range from 895.1-6,015.8 x 10(3) cfu/m(3)
      (median 1,055.3 x 10(3) cfu/m(3)). During processing of chamomile herb they were
      much lower and varied within a range from 0.88-295.6 x 10(3) cfu/m(3) (median
      27.3 x 10(3) cfu/m(3)). Gram-negative bacteria distinctly prevailed during
      processing of peppermint leaves, forming 46.4-88.5 % of the total airborne
      microflora. During processing of chamomile herb, Gram-negative bacteria were
      dominant at 3 out of 6 sampling sites forming 54.7-75.3 % of total microflora,
      whereas at the remaining 3 sites the most common were fungi forming 46.2-99.9 %
      of the total count. The species Pantoea agglomerans (synonyms: Erwinia herbicola,
      Enterobacter agglomerans ), having strong allergenic and endotoxic properties,
      distinctly prevailed among Gram-negative isolates. Among fungi, the most common
      species was Alternaria alternata. The concentrations of airborne dust and
      endotoxin determined on the examined herb farms were large. The concentrations of
      airborne dust during peppermint and chamomile processing ranged from 86.7-958.9
      mg/m(3), and from 1.1-499.2 mg/m(3), respectively (medians 552.3 mg/m(3) and 12.3
      mg/m(3)). The concentrations of airborne endotoxin determined during peppermint
      and chamomile processing were within a wide range 1.53-208.33 microg/m(3) and
      0.005-2604.19 microg/m(3) respectively (medians 57.3 microg/m(3) and 0.96
      microg/m(3)). In conclusion, farmers cultivating peppermint are exposed during
      processing of this herb to large concentrations of airborne microorganisms, dust
      and endotoxin posing a risk of work-related respiratory disease. The exposure to
      bioaerosols during processing of chamomile is lower; nevertheless, peak values
      create a respiratory risk for exposed farmers.

PMID- 16457487
TI  - Immunostimulative effects of repeated inhalation exposure to microvesicle-bound
      endotoxin of Pantoea agglomerans.
AB  - Rabbits exposed repeatedly to aerosols of endotoxin-containing microvesicles
      (ECMV) of the outer membrane of the Pantoea agglomerans strain isolated from
      airborne grain dust showed a large increase in the concentration of circulating
      cytokines: total interferon (IFN), interleukin-1 alpha (IL-1 alpha), and tumor
      necrosis factor alpha (TNF alpha). The increase was significantly higher compared
      to animals exposed to control saline (p < 0.001). Aerosol exposure to ECMV also
      induced the formation of specific precipitin antibodies and lymphocyte
      activation. The results indicate strong immunomodulative properties of ECMVs
      produced in nature by Pantoea agglomerans bacteria, and heavily contaminating
      organic dusts.

PMID- 16457488
TI  - Electron microscopic examination of dental unit waterlines biofilm.
AB  - Using the transmission electron microscope, the ultrastructural examination was
      conducted to detect the presence of bacterial biofilm on the inner surfaces of
      the tubing in dental unit waterlines (DUWL). Samples for examination were taken
      from the tubes providing water to high-speed and slow-speed handpieces, and to an
      air-water syringe before application of a disinfection procedure. The microscopic
      analysis made it possible to find the biofilm in all the tubes in the dental unit
      which were not pre-disinfected. In these samples, no significant differences were
      found between high-speed, slow-speed and air-water lines.

PMID- 16457489
TI  - Cutaneous manifestation of giardiasis - case report.
AB  - Giardia intestinalis is a protozoan parasiting the gastrointestinal tract of
      vertebrate hosts widely distributed throughout the world. Patients with
      giardiasis are usually asymptomatic but the presence of the parasite may lead to
      a variety of clinical manifestations, including skin lesions. In this report we
      present a case of a 31-year-old female patient with skin lesions of granuloma
      annulare type confirmed by a skin biopsy, who was diagnosed with giardiasis. The
      clearance of the skin lesions after antiparasite treatment seems to support
      correlation between dermatological symptoms and infection with Giardia
      intestinalis .

PMID- 16457490
TI  - Co-existance of toxoplasmosis and neuroborreliosis - a case report.
AB  - The 53-year-old woman was initially diagnosed with multiple sclerosis, despite
      the fact that she did not really meet the clinical criteria. Her only symptoms
      were clumsiness and weakness of the right extremities. Being a veterinary
      research worker she had been exposed to infectious material. In 1995, she was
      diagnosed with ELISA as having toxoplasmosis and treated as such. In 2002, after
      the infectious, flu-like disease, she revealed arthritis and drowsiness, also
      with memory and language impairment. The patient continued to have symptoms
      consistent with previously examined clumsiness. She was diagnosed with Lyme via
      ELISA and PCR, and treated. She made a full recovery from acute symptoms. After a
      few months, neurological and neuropsychological examinations were performed. On
      the background of mild cognitive decline apraxia and difficulties of attention
      were noted as the main problems. A apraxia of the right hand complicated the
      patient's life and depreciated her quality of life. The patient underwent MRI
      examination. FSE, FAST and FLAIR sequences were made. The MRI demonstrated the
      appearance of several small hyperintense lesions in the white matter of the left
      and right frontal and left parietal lobe. These lesions were typical of the post
      inflammatory leucoencephalopathy. Additionally, a ring-shaped, low-intensity
      lesion in the posterior part of the left parietal lobe was noticed. The lesion
      was 8 mm in diameter and described to be an old toxoplasmosis lesion. The patient
      had been treated and the symptoms consistent with Lyme disease resolved. Patient
      continues to have symptoms consistent with focal destruction of the parietal
      lobe. Over the past six months, she has not progressed and relapsed in a manner
      that is consistent with MS.

PMID- 16457492
TI  - Airborne pollen of Olea in five regions of Portugal.
AB  - The aim of this work was to study spatial and temporal distribution of Olea
      europeae airborne pollen in different Portuguese regions: Reguengos de Monsaraz
      (south); Bairrada (west); Braga (northwest); Valenca do Douro and Foz Coa (north
      east). Airborne pollen sampling was conducted from 1998-2003 using "Cour" type
      samplers located in each region. The main pollen season (MPS) of Olea lasted on
      average 36 days and occurred from late April until middle-to-end of June. During
      the studied period, inter-annual variations among and within regions, concerning
      the total annual pollen counts and the beginning, peak and ending dates of the
      MPS, were reported. Reguengos de Monsaraz and Bairrada registered the earliest
      MPS starting date, followed by Valenca do Douro and Foz-Coa, and the latest date
      was verified in Braga that also had the shortest MPS. Reguengos de Monsaraz
      presented the longest MPS with the highest differences in the beginning and
      ending dates, but minimum differences in the dates of the maximum pollen peak.
      Our results showed an increase in the Olea annual pollen index, from north to
      south, and from the west to the east regions of the country.

PMID- 16457491
TI  - Annual variation of fungal spores in atmosphere of Porto: 2003.
AB  - The seasonal distribution of fungal spore concentration in the city of Porto,
      Portugal, was continuously studied, from 1 January to 31 December 2003, using a 7
      day volumetric Burkard trap. In Portugal, aerobiological studies are scarce, and
      to our knowledge there are no published data on the atmospheric concentration of
      fungal spores. The aim of this work therefore is to initiate the aeromycological
      studies in Porto. The total airborne spore concentration fluctuated between 2 and
      2,198 spores/m(3) per day with an daily mean of 403 spores/m(3). The highest
      airborne spore concentration was found during the summer and the early autumn,
      while the lowest concentration was registered during the winter. A range of
      allergenic and phytopathogenic fungal spores was present in the atmosphere of
      Porto throughout the entire year, although in different concentrations. Among the
      22 fungal spore types identified Cladosporium (74.5 %), Ganoderma (11.7 %),
      Aspergillaceae (2.9 %), Ustilago (2.5 %), Coprinus (1.5 %), Alternaria (1.3 %)
      and Botrytis (1.3 %) were the most frequent. Seasonally, spore levels of
      Cladosporium and Alternaria peaked in the autumn and winter, Ganoderma peaked
      toward autumn, whilst spore levels of the basidiomycete Coprinus fluctuated
      throughout the year. The total spore concentration was negatively correlated with
      wind speed and positively correlated with temperature and relative humidity.

PMID- 16457493
TI  - Application of specific primers in the diagnosis of Encephalitozoon spp.
AB  - In our experiment, 3 species-specific primer pairs cultivated in cell lines were
      used: Encephalitozoon cuniculi -specific primer pairs (ECUNF and ECUNR),
      Encephalitozoon hellem -specific primer pairs (EHELF and EHELR), and
      Encephalitozoon intestinalis -specific primer pairs (SINTF and SINTR). The PCR
      products were estimated to be 550 bp in E. cuniculi , 547 bp in E. hellem and 545
      bp in E. intestinalis respectively, which can prove the precision and reliability
      of this method in the species identification of the genus Encephalitozoon. All 3
      primer pairs were species-specific and none of them amplified gene sequences from
      other Encephalitozoon spp.

PMID- 16457495
TI  - Model for performing institutional animal care and use committee: continuing
      review of animal research.

PMID- 16457494
TI  - Evaluation of teeth loss among workers in the laminate and composite materials
      department of aircraft factory.
AB  - Liquid epoxide resins, solvents and solvent-modified epoxide resins, as well as
      hardeners for epoxide resins, appear to be skin and mucosa irritants of different
      intensity and possibly have allergenic properties. Therefore, it is required that
      the employees are qualified and industrial safety rules are followed when these
      substances are in use in the manufacturing process. Our study evaluated the state
      of dentition and analysed the loss of teeth in the workers of the laminate and
      composite materials department of aircraft factory. The research has been carried
      out in a group of 114 workers, which consisted of 88 men and 26 women 20 to 61
      years old. The control group consisted of 41 workers of the administration
      department in the aircraft factory who did not have any contact with chemical
      compounds. The workers in the studied group are characterised as having an
      unsatisfactory state of dentition, as shown by the high rate of lost teeth (74
      %). Statistically significant difference between the studied group and the
      control was found when the relationship between the number of lost molar teeth in
      women in the studied group and those in the control group is taken into
      consideration, a statistically significant difference appears to refer to teeth
      46 and 27. The same statistically important correlation between men in the
      control and studied groups concerns teeth 16. The research data shows that
      incisor teeth are the least frequently extracted teeth in the whole population
      studied. Statistically significant differences can be noted for teeth 21 and 23
      between the women in the control group and those in the studied one. Future
      studies are necessary to assess the potential relationship between the loss of
      teeth among workers of the department of laminate and composite materials of
      aircraft factory and their workplace.

PMID- 16457496
TI  - Diarrhea and peritonitis due to traumatic perforation of the stomach in a rhesus
      macaque (hardware disease).

PMID- 16457497
TI  - Leiomyosarcoma of the uterus in a rhesus monkey with iliac lymph node metastasis,
      endosalpingiosis, and endometriosis.

PMID- 16457498
TI  - Effect of bleeding site on clinical pathologic parameters in Sprague-Dawley rats:
      retro-orbital venous plexus versus abdominal aorta.

PMID- 16457499
TI  - The sand rat (Psammomys obesus): morphologic, physiologic, and biochemical
      characteristics of a model for type-II diabetes mellitus.

PMID- 16457500
TI  - Comparison of anesthetic effects of Telazol-xylazine xylazine, Telazol-xylazine
      butorphanol, and Telazol-xylazine-azaperone combinations in swine.

PMID- 16457501
TI  - Anesthetic agents for use in the invertebrate sea snail, Aplysia californica.

PMID- 16457502
TI  - Effect of cage size on sexual behavior pattern in male rats.

PMID- 16457503
TI  - Automatic feeder for newborn rat use within l2 hours of birth.

PMID- 16457504
TI  - Diagnosis of low level coccidiosis (Eimeria) infection in laboratory rabbits:
      evaluation of detection methods.

PMID- 16457505
TI  - Splenic stromal myoid cell sarcoma in an aged F344 rat.

PMID- 16457506
TI  - Antioxidants simplified: some species differences.

PMID- 16457507
TI  - New technique for catheterization of the sacral canal in rabbits.

PMID- 16457508
TI  - Interpretive summary of the Report of the AVMA Panel on Euthanasia.

PMID- 16457509
TI  - Accreditation of laboratory animal facilities: the beginning.

PMID- 16457510
TI  - Anesthetic effects of Telazol and combinations of ketamine-xylazine and Telazol
      ketamine-xylazine in ferrets.

PMID- 16457511
TI  - Comparison of five anesthetic agents administered intraperitoneally in the
      laboratory rat.

PMID- 16457512
TI  - Effect of water treatment and Pseudomonas infection on mortality in irradiated,
      viral antibody-free mice.

PMID- 16457513
TI  - Evaluation of microenvironmental conditions and noise generation in three
      individually ventilated rodent caging systems and static isolator cages.

PMID- 16457514
TI  - Improved catheterization technique for repeated intravenous dosing and serial
      blood sampling in rabbits.

PMID- 16457515
TI  - Eradication of Aspiculuris tetraptera, using fenbendazole-medicated food.

PMID- 16457516
TI  - Ureteral urinary calculus and hydronephrosis in a New Zealand white rabbit.

PMID- 16457517
TI  - Colon biopsy in the management of chronic diarrhea in rhesus macaques.

PMID- 16457518
TI  - Novel, fast method for ear vein catheterization in young pigs.

PMID- 16457519
TI  - A successful animal adoption program: observations on the Animal Care Facility
      program at the University of California, San Francisco.

PMID- 16457521
TI  - Experimental fetal neurosurgery: the normal neurology of neonatal lambs and
      abnormal findings after in utero manipulation.

PMID- 16457520
TI  - Effect of confinement in metabolism stalls on cortisol, antibody production, and
      antibody-dependent cell-mediated cytotoxicity in lambs.

PMID- 16457522
TI  - Comparison of blood pressure measurements using vascular access ports and
      conventional catheters.

PMID- 16457523
TI  - Comparison of specific-pathogen-free and conventional rats under surgical and
      experimental stressors.

PMID- 16457524
TI  - Variability of serum thyroid hormone concentrations in subpopulations of male
      cynomolgus macaques.

PMID- 16457525
TI  - Cardiac hypertrophy in a tamarin (Saguinus mystax).

PMID- 16457526
TI  - Ophthalmic lesions in dexamethasone-treated rats naturally infected with
      sialodacryoadenitis virus while concurrently used for Pneumocystis carinii
      propagation.

PMID- 16457527
TI  - Percutaneous spinal catheterization in the rabbit.

PMID- 16457528
TI  - Colonic epidermoid cysts in two beagles.

PMID- 16457529
TI  - Perinephric pseudocysts in a squirrel monkey.

PMID- 16457530
TI  - Effective mentoring of laboratory animal science professionals.

PMID- 16457531
TI  - Effects of observation techniques on the behavior of adult rhesus macaques.

PMID- 16457532
TI  - Effect of social rearing conditions on affiliative and reproductive behaviors of
      adult unimale/multifemale grouped rhesus macaques: a case study.

PMID- 16457533
TI  - Abdominal leiomyosarcoma in a rhesus macaque.

PMID- 16457535
TI  - An activity cage for baboons, part II: long-term effects and management issues.

PMID- 16457534
TI  - An activity cage for baboons, part I.

PMID- 16457536
TI  - Pancreatitis and pregnancy toxemia in a New Zealand white rabbit.

PMID- 16457537
TI  - Novel restraint device for oral dosing of rabbits.

PMID- 16457538
TI  - Intraocular leiomyosarcoma in a Fischer 344 rat.

PMID- 16457539
TI  - Cutaneous papilloma arising from trichoepitheliomas in a guinea pig.

PMID- 16457540
TI  - Soft surfaces: a factor in feline psychological well-being.

PMID- 16457541
TI  - Malignant melanoma in a xoloitzcuintli dog.

PMID- 16457543
TI  - Use of computational fluid dynamics to assess air distribution patterns in animal
      rooms.

PMID- 16457542
TI  - Perioperative care for laboratory animals: preoperative and postoperative
      principles and applications.

PMID- 16457544
TI  - Hearing conservation and compact personal stereos in laboratory animal
      facilities.

PMID- 16457546
TI  - A comparison of two fecal collection methods to monitor parasitism in socially
      housed rhesus monkeys.

PMID- 16457545
TI  - Evaluation of a transdermal fentanyl system in the dog.

PMID- 16457547
TI  - Appropriate use of radiopaque contrast media to verify intracerebroventricular
      cannula placement in the live rat.

PMID- 16457548
TI  - Use of the BAAM Mark VI for blind oral intubation in the rabbit.

PMID- 16457549
TI  - Technique for telemetric determination of blood pressure and heart rate in the
      conscious, pregnant rabbit.

PMID- 16457550
TI  - Age and social experience affect the breeding performance of subadult male rhesus
      monkeys (Macaca mulatta).

PMID- 16457551
TI  - Cysticercosis in prairie dogs.

PMID- 16457552
TI  - A case of spontaneous monoamniotic twins in a Sprague-Dawley rat.

PMID- 16457553
TI  - Justifying the number of animals in IACUC proposals.

PMID- 16457554
TI  - Guidelines for Institutional Animal Care and Use Committees: consideration of
      alternatives.

PMID- 16457555
TI  - Establishment of an animal alternatives committee.

PMID- 16457556
TI  - Search for animal alternatives and the role of the information specialist.

PMID- 16457557
TI  - Proposed IACUC guidelines for the review of rodent toxicology studies.

PMID- 16457558
TI  - Implementation of the protocol: a process.

PMID- 16457559
TI  - Laparoscopic ovariectomy of miniature swine.

PMID- 16457560
TI  - Two-part intubation catheter: a guide to endotracheal intubation in pigs.

PMID- 16457561
TI  - Radiographic imaging of rodents using a portable mammographic system.

PMID- 16457562
TI  - Tympanic infrared thermometry to determine cat body temperature.

PMID- 16457563
TI  - Characterization and quantification of microenvironmental contaminants in
      isolator cages with a variety of contact beddings.

PMID- 16457564
TI  - Use of epinephrine auto-injectors for acute anaphylactic reactions in an animal
      care facility.

PMID- 16457565
TI  - Diagnostic exercise: ocular lesions in hypophysectomized rats.

PMID- 16457566
TI  - Is decapitation a humane method of euthanasia in rodents? A critical review.

PMID- 16457567
TI  - The use of computational fluid dynamics for modeling airflow design in a kennel
      facility.

PMID- 16457568
TI  - An animal facility database management system using a Macintosh computer and
      commercially available software.

PMID- 16457569
TI  - A comparison of four methods for sterilizing surgical instruments for rodent
      surgery.

PMID- 16457570
TI  - A unique swivel-tether system for continuous i.v. infusions in freely mobile
      unrestrained rabbits.

PMID- 16457572
TI  - Lipid physiology: species differences.

PMID- 16457571
TI  - The behavioral response of individually caged baboons to feeding enrichment and
      the standard diet: a preliminary report.

PMID- 16457573
TI  - Methylmethacrylate-associated thermal injury during cranioplasty in a nonhuman
      primate.

PMID- 16457574
TI  - Diagnostic exercise: apparent corneal occlusion in a New Zealand white rabbit.

PMID- 16457575
TI  - Eradication of pinworms from rats by using ivermectin in the drinking water.

PMID- 16457576
TI  - A milking device for rats.

PMID- 16457577
TI  - The 4th R of research.

PMID- 16457578
TI  - A comparative study of an automated diagnostic system with standard manual
      techniques for microbiological water analysis in an animal facility.

PMID- 16457580
TI  - Comparison of xylazine and midazolam as intramuscular CNS depressants in dogs.

PMID- 16457579
TI  - Behavioral evaluation of spatially enhanced caging for laboratory rats at high
      density.

PMID- 16457581
TI  - Initial validation of a software program for measuring canine
      electrocardiographic parameters.

PMID- 16457582
TI  - Pyrolytic incineration of medical waste containing animal carcasses may result in
      toxic barium ash levels.

PMID- 16457584
TI  - Vomiting and diarrhea in a cat colony.

PMID- 16457583
TI  - Vaginal (copulation) plugs in laboratory rodents: a review.

PMID- 16457585
TI  - Health Research TV Cable Series.

PMID- 16457586
TI  - Cancer Vaccines 2005: Barriers, Endpoints & Opportunities, October 5 - 7, 2005,
      New York, USA. Abstracts.

PMID- 16457587
TI  - Gene-specific characterization of human histone H2B by electron capture
      dissociation.
AB  - The basis set of protein forms expressed by human cells from the H2B gene family
      was determined by Top Down Mass Spectrometry. Using Electron Capture Dissociation
      for MS/MS of H2B isoforms, direct evidence for the expression of unmodified
      H2B.Q, H2B.A, H2B.K/T, H2B.J, H2B.E, H2B.B, H2B.F, and monoacetylated H2B.A was
      obtained from asynchronous HeLa cells. H2B.A was the most abundant form, with the
      overall expression profile not changing significantly in cells arrested in
      mitosis by colchicine or during mid-S, mid-G2, G2/M, and mid-G1 phases of the
      cell cycle. Modest hyperacetylation of H2B family members was observed after
      sodium butyrate treatment.

PMID- 16457589
TI  - Precise characterization of human histones in the H2A gene family by top down
      mass spectrometry.
AB  - Top Down analysis revealed that at least fourteen genes encoding histone H2A are
      coexpressed in HeLa cells. Characterization of these species revealed that all
      except H2A.Z and H2A.F/Z were alpha-N-acetylated, H2A.O and H2A.C,D,I,N,P were
      the most abundant, and those exceeding approximately 10% abundance lacked post
      translational modifications. This unequivocal identification of H2A forms
      illustrates the advantages of Top Down Mass Spectrometry and provides a global
      perspective of H2A regulation through the cell cycle.

PMID- 16457588
TI  - Mass spectrometric characterization of human histone H3: a bird's eye view.
AB  - The modification of H3 in asynchronous HeLa cells was profiled using Top Down
      Mass Spectrometry. A broad distribution of species differing by 14 Da and
      containing less than 3% unmodified protein was observed for all three variants.
      Species of up to +168 Da were observed for H3.1, and fragmentation of all species
      by Electron Capture Dissociation (ECD) revealed approximately 5% methylation of
      K4 and approximately 50% dimethylation of K9. K14 and K23 were major sites of
      acetylation. H3.3 was slightly hypermodified with the apex of the distribution
      shifted by approximately +14 Da compared to H3.1. H3.1 (50% and 15%) from
      colchicine-treated cells was monophosphorylated and diphosphorylated,
      respectively, with equivalent modification of S10 and S28.

PMID- 16457590
TI  - Comparison of software tools to improve the detection of carcinogen induced
      changes in the rat liver proteome by analyzing SELDI-TOF-MS spectra.
AB  - A common animal model of chemical hepatocarcinogenesis was used to demonstrate
      the potential identification of carcinogenicity related protein
      signatures/biomarkers. Therefore, an animal study in which rats were treated with
      the known liver carcinogen N-nitrosomorpholine (NNM) or the corresponding vehicle
      was evaluated. Histopathological investigation as well as SELDI-TOF-MS analysis
      was performed. SELDI-TOF-MS is an affinity-based mass spectrometry method in
      which subsets of proteins from biological samples are selectively adsorbed to a
      chemically modified surface. The proteins are subsequently analyzed with respect
      to their mass-charge ratios (m/z) by a time of flight (TOF) mass spectrometry
      (MS) approach. As data preprocessing of SELDI-TOF-MS spectra is essential,
      baseline correction, normalization, peak detection, and alignment of raw spectra
      were performed using either the Ciphergen ProteinChip Software 3.1 or functions
      implemented in the library PROcess of the BioConductor Project. Baseline
      correction and normalization algorithms of both tools lead to comparable results,
      whereas results after peak detection and alignment steps differed. Variability
      between technical and biological replicates was investigated. A linear mixed
      model with factors experimental group and time point was applied for each protein
      peak, taking into account the different correlation structure of technical and
      biological replicates. Alternatively, only median intensity values of technical
      replicates were used. Results of both models were similar and correlated well
      with those of the histopathological evaluation of the study. In conclusion,
      statistical analyses lead to comparable results, whereas parameter settings for
      preprocessing proved to be crucial.

PMID- 16457591
TI  - Decreased striatal levels of PEP-19 following MPTP lesion in the mouse.
AB  - PEP-19 is a neuronal calmodulin-binding protein, and as such, a putative
      modulator of calcium regulated processes. In the present study, we used
      proteomics technology approaches such as peptidomics and imaging MALDI mass
      spectrometry, as well as traditional techniques (immunoblotting and in situ
      hybridization) to identify PEP-19 and, specifically, to measure PEP-19 mRNA and
      protein levels in an animal model of Parkinson's disease. 1-Methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) administration in mice resulted in a
      significant decrease in striatal PEP-19 mRNA. Capillary nano-flow liquid
      chromatography electrospray mass spectrometry analysis of striatal tissue
      revealed a significant decrease of the PEP-19 protein level. Moreover, imaging
      MALDI mass spectrometry also showed that PEP-19 protein was predominantly
      localized to the striatum of the brain tissue cross sections. After MPTP
      administration, PEP-19 levels were significantly reduced by 30%. We conclude that
      PEP-19 mRNA and protein expression are decreased in the striatum of a common
      animal model of Parkinson's disease. Further studies are needed to show the
      specific involvement of PEP-19 in the neurodegeneration seen in MPTP lesioned
      animals. Finally, this study has shown that the combination of traditional
      molecular biology techniques with novel, highly specific and sensitive mass
      spectrometry methods is advantageous in characterizing molecular events of many
      diseases, including Parkinson's disease.

PMID- 16457592
TI  - Comparison of two proteomics techniques used to identify proteins regulated by
      gibberellin in rice.
AB  - Proteomics has become an essential methodology for large-scale analysis of
      proteins in various fields of plant biology. We compared two proteomics
      techniques, two-dimensional liquid chromatography (2D-LC) and fluorescence two
      dimensional difference gel electrophoresis (2D-DIGE), for their ability to
      identify proteins regulated by gibberellin (GA) in rice. Two-week-old rice
      seedlings were treated with or without 5 microM GA3 for 48 h and proteins
      extracted from the basal region of the leaf sheath. After separation of the
      proteins by the two techniques, the amino acid sequences of GA3-responsive
      proteins were analyzed using a protein sequencer and mass spectrometry. 2D-LC and
      2D-DIGE were able to resolve 1248 protein fractions and 1500 proteins,
      respectively. Out of these, 2D-LC identified 9 proteins that were up-regulated
      and 9 that were down-regulated by GA treatment; 2D-DIGE identified 4 up-regulated
      and 4 down-regulated proteins. The two techniques detected overlapping sets of
      proteins. For example, cytosolic glyceraldehyde-3-phosphate dehydrogenase and
      photosystem II oxygen-evolving complex protein were identified as GA3-regulated
      proteins by both methods. In addition, these two methods uncovered GA3-regulated
      unknown proteins which had not been reported previously, and novel proteins which
      are not detected in 2D-PAGE followed by Coomassie brilliant blue staining. These
      results suggest that these two methods are among some of the very useful tools
      for detecting proteins that may function in various physiological and
      developmental processes in plants.

PMID- 16457593
TI  - Normalization approaches for removing systematic biases associated with mass
      spectrometry and label-free proteomics.
AB  - Central tendency, linear regression, locally weighted regression, and quantile
      techniques were investigated for normalization of peptide abundance measurements
      obtained from high-throughput liquid chromatography-Fourier transform ion
      cyclotron resonance mass spectrometry (LC-FTICR MS). Arbitrary abundances of
      peptides were obtained from three sample sets, including a standard protein
      sample, two Deinococcus radiodurans samples taken from different growth phases,
      and two mouse striatum samples from control and methamphetamine-stressed mice
      (strain C57BL/6). The selected normalization techniques were evaluated in both
      the absence and presence of biological variability by estimating extraneous
      variability prior to and following normalization. Prior to normalization,
      replicate runs from each sample set were observed to be statistically different,
      while following normalization replicate runs were no longer statistically
      different. Although all techniques reduced systematic bias to some degree,
      assigned ranks among the techniques revealed that for most LC-FTICR-MS analyses
      linear regression normalization ranked either first or second. However, the lack
      of a definitive trend among the techniques suggested the need for additional
      investigation into adapting normalization approaches for label-free proteomics.
      Nevertheless, this study serves as an important step for evaluating approaches
      that address systematic biases related to relative quantification and label-free
      proteomics.

PMID- 16457594
TI  - Determination and comparison of the baseline proteomes of the versatile microbe
      Rhodopseudomonas palustris under its major metabolic states.
AB  - Rhodopseudomonas palustris is a purple nonsulfur anoxygenic phototrophic
      bacterium that is ubiquitous in soil and water. R. palustris is metabolically
      versatile with respect to energy generation and carbon and nitrogen metabolism.
      We have characterized and compared the baseline proteome of a R. palustris wild
      type strain grown under six metabolic conditions. The methodology for proteome
      analysis involved protein fractionation by centrifugation, subsequent digestion
      with trypsin, and analysis of peptides by liquid chromatography coupled with
      tandem mass spectrometry. Using these methods, we identified 1664 proteins out of
      4836 predicted proteins with conservative filtering constraints. A total of 107
      novel hypothetical proteins and 218 conserved hypothetical proteins were
      detected. Qualitative analyses revealed over 311 proteins exhibiting marked
      differences between conditions, many of these being hypothetical or conserved
      hypothetical proteins showing strong correlations with different metabolic modes.
      For example, five proteins encoded by genes from a novel operon appeared only
      after anaerobic growth with no evidence of these proteins in extracts of
      aerobically grown cells. Proteins known to be associated with specialized growth
      states such as nitrogen fixation, photoautotrophic, or growth on benzoate, were
      observed to be up-regulated under those states.

PMID- 16457595
TI  - Proteomic profiling of regionalized proteins in rat epididymis indicates
      consistency between specialized distribution and protein functions.
AB  - The epididymis is a key structure of the male reproductive system; its function
      is to mature, transport, and store sperm. Most of the research examining the
      epididymis to date has been limited to the study of the secreted proteins
      involved in the maturation of spermatozoa. However, it is also very important to
      understand the protein components, regulation and function of the tissue itself
      since these are the basis for all of its physiological processes. We investigated
      the differential expression of proteins among the caput, corpus, and cauda
      regions of rat epididymis and considered the possible links between the
      localization of these proteins and the different functions of these epididymal
      regions. High-resolution 2-D gel electrophoresis followed by mass spectrometry
      (MS) revealed 28 distinct proteins whose expression levels varied from the caput
      to the cauda epididymis. Sixteen of them were reported for first time to be
      expressed in the epididymis. Expression patterns of some proteins were validated
      by Northern blot or Western blot. Immunohistochemistry revealed that inducible
      carbonyl reductase (iCR), an important enzyme in the anti-oxidative system,
      exhibits primary and cell-type specific distribution in the distal cauda region.
      Moreover, analysis of iCR transcription in castrated animals showed that its
      expression is androgen-dependent. Together with its known functions, iCR may also
      be involved in androgen metabolism and maintaining a steady microenvironment in
      the duct of epididymis.

PMID- 16457596
TI  - Proteomic analysis of serum associated fucosylated glycoproteins in the
      development of primary hepatocellular carcinoma.
AB  - Changes in N-linked glycosylation are known to occur during the development of
      cancer. For example, increased branching of oligosaccharides has been associated
      with metastasis and has been correlated to tumor progression in human cancers of
      the breast, colon and melanomas. Increases in core fucosylation have also been
      associated with the development of hepatocellular carcinoma (HCC). Chronic
      infection with the hepatitis B virus is associated with more than 55% of all
      cases of hepatocellular carcinoma. We show here that increased levels of core
      fucosylation can be observed via glycan analysis of total serum and are
      associated with the development of HCC. In a blinded study, the serum
      glycoproteins derived from people diagnosed with HBV induced liver cancer were
      found to possess a dramatically higher level of fucosylation. This change occurs
      on both immunoglobulin molecules and on other serum glycoproteins. Targeted
      glycoproteomic analysis was used to identify those glycoproteins that are
      hyperfucosylated in cancer. In total, 19 proteins were found to be
      hyperfucosylated in cancer. The potential of these proteins as biomarkers of
      cancer is discussed.

PMID- 16457597
TI  - Predicting protein-protein interactions from sequences in a hybridization space.
AB  - To understand the networks in living cells, it is indispensably important to
      identify protein-protein interactions on a genomic scale. Unfortunately, it is
      both time-consuming and expensive to do so solely based on experiments due to the
      nature of the problem whose complexity is obviously overwhelming, just like the
      fact that "life is complicated". Therefore, developing computational techniques
      for predicting protein-protein interactions would be of significant value in this
      regard. By fusing the approach based on the gene ontology and the approach of
      pseudo-amino acid composition, a predictor called "GO-PseAA" predictor was
      established to deal with this problem. As a showcase, prediction was performed on
      6323 protein pairs from yeast. To avoid redundancy and homology bias, none of the
      protein pairs investigated has > or = 40% sequence identity with any other. The
      overall success rate obtained by jackknife cross-validation was 81.6%, indicating
      the GO-PseAA predictor is very promising for predicting protein-protein
      interactions from protein sequences, and might become a useful vehicle for
      studying the network biology in the postgenomic era.

PMID- 16457598
TI  - Comprehensive protein profiling by multiplexed capillary zone electrophoresis
      using cross-linked polyacrylamide coated capillaries.
AB  - We have recently developed a new process to create cross-linked polyacrylamide
      (CPA) coatings on capillary walls to suppress protein-wall interactions. Here, we
      demonstrate CPA-coated capillaries for high-efficiency (>2 x 10(6) plates per
      meter) protein separations by capillary zone electrophoresis (CZE). Because CPA
      virtually eliminates electroosmotic flow, positive and negative proteins cannot
      be analyzed in a single run. A "one-sample-two-separation" approach is developed
      to achieve a comprehensive protein analysis. High throughput is achieved through
      a multiplexed CZE system.

PMID- 16457599
TI  - Comparative proteomics of nasal fluid in seasonal allergic rhinitis.
AB  - A comparative proteomic approach was applied to examine nasal lavage fluid (NLF)
      from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects
      (controls, n = 5). NLF samples were taken both before allergy (pollen) season and
      during season, and proteins were analyzed by two-dimensional gel electrophoresis
      (2-DE) and matrix assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected
      and quantified. During allergy season, the levels of six sialylated isoforms of
      PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than
      controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP),
      including a previously undescribed form with N-linked glycosylation, and of
      cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are
      two endogenous proteinase inhibitors. By contrast, the levels of an acidic form
      of alpha-1-antitrypsin were higher in SAR patients than controls. One previously
      unidentified NLF protein was found in all samples from the SAR patients during
      allergy season but not in any sample before allergy season: this protein was
      identified as eosinophil lysophospholipase (Charcot-Leyden crystal
      protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed
      removal of Met and acetylation of Ser. Altogether, these findings illustrate the
      potential use of proteomics for identifying protein changes associated with
      allergic rhinitis and for revealing post-translational modifications of such new
      potential markers of allergic inflammation.

PMID- 16457600
TI  - Saccharomyces cerevisiae mitoproteome plasticity in response to recombinant
      alternative ubiquinol oxidase.
AB  - The energy-dissipating alternative oxidase (AOX) from Hansenula anomala was
      expressed in Saccharomyces cerevisiae. The recombinant AOX was functional. A
      comparative analysis by two-dimensional differential in-gel electrophoresis (2D
      DIGE) of mitochondrial protein patterns found in wild-type and recombinant AOX
      strains was performed. 60 proteins exhibiting a significant difference in their
      abundance were identified. Interestingly, proteins implicated in major metabolic
      pathways such as Krebs cycle and amino acid biosynthesis were up-regulated.
      Surprisingly, an up-regulation of the respiratory-chain complex III was
      associated with a down-regulation of the ATP synthase complex.

PMID- 16457601
TI  - Combined chemical and enzymatic stable isotope labeling for quantitative
      profiling of detergent-insoluble membrane proteins isolated using Triton X-100
      and Brij-96.
AB  - Effective quantitative profiling of detergent-insoluble membrane proteins using
      high-throughput mass spectrometry (MS)-based proteomics would allow a better
      understanding of physiological and pathological processes that take place at the
      cell surface. To increase the coverage of proteins present in detergent-resistant
      membrane microdomains (DRMMs), a combination of 16O/18O and isotope coded
      affinity tags (ICAT) labeling was used in a comparative analysis of detergent
      insoluble membrane proteins isolated from rat basophilic leukemia cells (RBL
      2H3), with either Triton X-100 or Brij-96. The analysis resulted in the
      quantification of 738 unique proteins from Triton X-100 and Brij-96 isolated
      DRMMs, significantly exceeding the number of proteins quantified from either
      single labeling technique. Twenty-five noncysteine-containing proteins were
      quantified, as well as 32 cysteine-containing proteins that would have been
      missed if either 16O/18O or ICAT labeling had been used exclusively, which
      illustrate better proteome coverage and enhanced ability to quantitate. The
      comparative analysis revealed that proteins were more readily extracted using
      Triton X-100 than Brij-96; however, Triton X-100 also extracted larger quantities
      of non-DRMMs-associated proteins. This result confirms previous, targeted studies
      suggesting that DRMMs isolated using Triton X-100 and Brij-96 differ in their
      protein content.

PMID- 16457603
TI  - Identification of subunit-subunit interactions in bacteriophage P22 procapsids by
      chemical cross-linking and mass spectrometry.
AB  - Viral capsids are dynamic structures which self-assemble and undergo a series of
      structural transformations to form infectious viruses. The dsDNA bacteriophage
      P22 is used as a model system to study the assembly and maturation of icosahedral
      dsDNA viruses. The P22 procapsid, which is the viral capsid precursor, is
      assembled from coat protein with the aid of scaffolding protein. Upon DNA
      packaging, the capsid lattice expands and becomes a stable virion. Chemical cross
      linking analyzed by mass spectrometry was used to identify residue specific inter
      and intra-subunit interactions in the P22 procapsids. All the intersubunit cross
      links occurred between residues clustered in a loop region (residues 157-207)
      which was previously identified by mass spectrometry based on hydrogen/deuterium
      exchange and biochemical experiments. DSP and BS3 which have similar distance
      constraints (12 angstroms and 11.4 angstroms, respectively) cross-linked the same
      residues between two subunits in the procapsids (K183-K183), whereas DST, a
      shorter cross-linker, cross-linked lysine 175 in one subunit to lysine 183 in
      another subunit. The replacement of threonine with a cysteine at residue 182
      immediately adjacent to the K183 cross-linking site resulted in slow spontaneous
      disulfide bond formation in the procapsids without perturbing capsid integrity,
      thus suggesting flexibility within the loop region and close proximity between
      neighboring loop regions. To build a detailed structure model, we have predicted
      the secondary structure elements of the P22 coat protein, and attempted to thread
      the prediction onto identified helical elements of cryoEM 3D reconstruction. In
      this model, the loop regions where chemical cross-linkings occurred correspond to
      the extra density (ED) regions which protrude upward from the outside of the
      capsids and face one another around the symmetry axes.

PMID- 16457602
TI  - Characterization of the mouse brain proteome using global proteomic analysis
      complemented with cysteinyl-peptide enrichment.
AB  - We report a global proteomic approach for analyzing brain tissue and for the
      first time a comprehensive characterization of the whole mouse brain proteome.
      Preparation of the whole brain sample incorporated a highly efficient cysteinyl
      peptide enrichment (CPE) technique to complement a global enzymatic digestion
      method. Both the global and the cysteinyl-enriched peptide samples were analyzed
      by SCX fractionation coupled with reversed phase LC-MS/MS analysis. A total of
      48,328 different peptides were confidently identified (>98% confidence level),
      covering 7792 nonredundant proteins ( approximately 34% of the predicted mouse
      proteome). A total of 1564 and 1859 proteins were identified exclusively from the
      cysteinyl-peptide and the global peptide samples, respectively, corresponding to
      25% and 31% improvements in proteome coverage compared to analysis of only the
      global peptide or cysteinyl-peptide samples. The identified proteins provide a
      broad representation of the mouse proteome with little bias evident due to
      protein pI, molecular weight, and/or cellular localization. Approximately 26% of
      the identified proteins with gene ontology (GO) annotations were membrane
      proteins, with 1447 proteins predicted to have transmembrane domains, and many of
      the membrane proteins were found to be involved in transport and cell signaling.
      The MS/MS spectrum count information for the identified proteins was used to
      provide a measure of relative protein abundances. The mouse brain peptide/protein
      database generated from this study represents the most comprehensive proteome
      coverage for the mammalian brain to date, and the basis for future quantitative
      brain proteomic studies using mouse models. The proteomic approach presented here
      may have broad applications for rapid proteomic analyses of various mouse models
      of human brain diseases.

PMID- 16457604
TI  - Metabolic phenotyping of nude and normal (Alpk:ApfCD, C57BL10J) mice.
AB  - Mice provide a range of important models of human disease. As part of a broad
      program of metabolic phenotyping (metabotyping) the effects of gender and strain
      upon urinary metabolite composition and variation have been investigated using 1H
      NMR spectroscopy and chemometrics in the Alpk:ApfCD, C57BL10J and the "Nude
      mouse". By using Principal Components Analysis (PCA) and Soft Independent
      Modeling by Class Analogy (SIMCA), characteristic metabotypes for each strain
      were produced for both male and female animals. In all three strains, female
      urinary metabolic profiles were characterized by higher lactate, trimethylamine-N
      oxide and lower trimethylamine concentrations relative to males. Both male and
      female Nude mice were phenotypically distinct from the Alpk:ApfCD and C57BL10J
      strains-the Nude mouse phenotypes being characterized by higher urinary
      creatinine, guanadinoacetic acid, dimethylamine, alpha-hydroxy-N-valeric acid and
      taurine levels and lower hippurate, citrate, creatine and succinate
      concentrations relative to those excreted by the two phenotypically normal mouse
      strains. These data show that Nude mice exhibit a wide variety of metabolic
      differences across a much wider range of pathways than has previously been
      thought, with potentially important considerations for studies that use the Nude
      mouse as a mouse model.

PMID- 16457605
TI  - Proteomic profiling for cellular responses to different concentrations of N
      methyl-N'-nitro-N-nitrosoguanidine.
AB  - Alkylating agent MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) can induce DNA
      damages which can lead to chromosomal aberrations, mutations, and cell death.
      Previous reports from our laboratory have found that low concentration of MNNG
      can induce nontargeted mutations (NTM) at undamaged bases in DNA, clustering of
      epidermal growth factor receptor (EGFR) and interference of EGFR mediated
      signaling, as well as activation of endoplasmic reticulum stress. Thus, the
      cellular responses to MNNG exposure are very complex, and can be triggered by
      signals originated from different compartments of the exposed cells. To further
      probe the molecular mechanisms involved in cellular responses to MNNG treatment,
      and to find potential biomarkers for MNNG induced stress condition, we performed
      proteomic analysis of whole cellular proteins from human amnion epithelial cells
      after exposing to MNNG at 3 different doses. More than 80 proteins were affected
      by MNNG treatment, and 71 proteins among them were identified using matrix
      assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry. These proteins take part in a wide variety of cellular processes
      including regulation of transcription, metabolism, cytoskeleton organization,
      cell cycle, cell proliferation, signal transduction, transportation, etc. The
      significance of these proteins in the genesis of MNNG induced cellular defensive
      response and hazardous effect remains to be elucidated, the results may also give
      a clue for biomarker search for monitoring the exposure risk of MNNG.

PMID- 16457606
TI  - Proteomic analysis of rice leaf sheath during drought stress.
AB  - Drought is one of the most severe limitations on the productivity of rainfed
      lowland and upland rice. To investigate the initial response of rice to drought
      stress, changes in protein expression were analyzed using a proteomic approach.
      Two-week-old rice seedlings were exposed to drought conditions from 2 to 6 days,
      and proteins were extracted from leaf sheaths, separated by two-dimensional
      polyacrylamide gel electrophoresis and stained with Coomassie brilliant blue.
      After drought stress for 2 to 6 days, 10 proteins increased in abundance and the
      level of 2 proteins decreased. The functional categories of these proteins were
      identified as defense, energy, metabolism, cell structure, and signal
      transduction. In addition to drought stress, accumulations of protein were
      analyzed under several different stress conditions. The levels of an actin
      depolymerizing factor, a light harvesting complex chain II, a superoxidase
      dismutase and a salt-induced protein were changed by drought and osmotic
      stresses, but not cold or salt stresses, or abscisic acid treatment. The effect
      of drought stress on protein in the leaf sheaths of drought-tolerant rice
      cultivar was also analyzed. The light harvesting complex chain II and the actin
      depolymerizing factor were present at high levels in a drought-tolerant rice
      cultivar before stress application. With drought stress, actin depolymerizing
      factor was expressed in leaf blades, leaf sheaths, and roots. These results
      suggest that actin depolymerizing factor is one of the target proteins induced by
      drought stress.

PMID- 16457607
TI  - Comparison of the protein profile of established and regressed hypertension
      induced left ventricular hypertrophy.
AB  - Established left ventricular hypertrophy (LVH) showed a significant alteration in
      the cardiac protein profile compared with normal heart. The main finding of this
      work was to identify proteins differently expressed in hypertension-induced LVH
      and the fact that after regression of LVH (histologically determined), the
      proteome still maintains a number of expressed proteins characteristic of the
      hypertrophied heart. These unrecovered proteins play an essential role in the
      energy production pathway, in cellular stress defense and also in hypertrophy
      regulation.

PMID- 16457608
TI  - Absolute myoglobin quantitation in serum by combining two-dimensional liquid
      chromatography-electrospray ionization mass spectrometry and novel data analysis
      algorithms.
AB  - To measure myoglobin, a marker for myocardial infarction, directly in human
      serum, two-dimensional liquid chromatography in combination with electrospray
      ionization mass spectrometry was applied as an analytical method. High-abundant
      serum proteins were depleted by strong anion-exchange chromatography. The
      myoglobin fraction was digested and injected onto a 60 mm x 0.2 mm i.d.
      monolithic capillary column for quantitation of selected peptides upon mass
      spectrometric detection. The addition of known amounts of myoglobin to the serum
      sample was utilized for calibration, and horse myoglobin was added as an internal
      standard to improve reproducibility. Calibration graphs were linear and
      facilitated the reproducible and accurate determination of the myoglobin amount
      present in serum. Manual data evaluation using integrated peak areas and an
      automated multistage algorithm fitting two-dimensional models of peptide elution
      profiles and isotope patterns to the mass spectrometric raw data were compared.
      When the automated method was applied, a myoglobin concentration of 460 pg/microL
      serum was determined with a maximum relative deviation from the theoretical value
      of 10.1% and a maximum relative standard deviation of 13.4%.

PMID- 16457609
TI  - Coupling the immobilized trypsin microreactor of monolithic capillary with muRPLC
      MS/MS for shotgun proteome analysis.
AB  - A nanoliter trypsin-based monolithic microreactor coupled with muRPLC-MS/MS was
      reported for shotgun proteome analysis. The proteins were rapidly digested by the
      microreactor, and the resulting protein digests were directly loaded onto a
      muRPLC column for separation followed with detection of the eluted peptides by
      tandem mass spectrometer. The digestion efficiency and stability of the
      microreactor was demonstrated by using bovine serum albumin as a model protein.
      When compared with an incubation time of more than 10 h by free trypsin in the
      conventional digestion approach, protein mixtures can be digested by the
      microreactor in several minutes. This system was applied to the analysis of the
      total cell lysate of Saccharomyces cerevisiae. After a Sequest database search, a
      total of 1578 unique peptides corresponding to 541 proteins were identified when
      590 ng yeast protein was digested by the microreactor with an incubation time of
      only 1 min.

PMID- 16457610
TI  - On-line concentration of microheterogeneous proteins by capillary electrophoresis
      using SDS and PEO as additives.
AB  - In this paper, we describe a method for analyzing large-volume protein samples
      using capillary electrophoresis in conjunction with laser-induced fluorescence
      detection (CE-LIF). To improve the stacking and separation efficiencies of
      proteins, we added either 0.01% sodium dodecyl sulfate (SDS) or 0.01%
      poly(ethylene oxide) (PEO) to the Tris-borate solutions (pH 10.0) used to prepare
      the protein samples. After injection of the large-volume samples (ca. 1.0 microL,
      0.1 microM), the proteins migrate against the electroosmotic flow (EOF) and enter
      the PEO zone; this process causes them to slow and stack at the boundary between
      the PEO and sample zones. As a result, the limits of detection (LODs) at a signal
      to-noise (S/N) of 3 for most proteins are sub-nM to several nM. For instance, the
      LOD (S/N = 3) for alpha-lactalbumin is 0.48 nM, which is an 84-fold sensitivity
      enhancement over the traditional method. By applying a short plug of 0.2% SDS
      prior to sample injection, a greater number of peaks, representing the
      microheterogeneity of the proteins, were resolved and the stacking efficiency of
      the proteins increased slightly. This method allowed us to detect 12 peaks when
      injecting a large volume of sample containing six model proteins (0.1 microM). We
      also analyzed the microheterogeneities of the proteins by using CE with UV-Vis
      absorption detection when injecting a large volume of sample containing six model
      proteins (1.0 microM) in the presence of a 1.0% SDS plug. The practical method is
      validated by the detection of human serum albumin in a urine sample, obtained
      from a healthy female, without sample pretreatment; its concentration was 0.18
      microM. We further demonstrate the capability of this method to detect low
      amounts of proteins through the detection of 45 nM hemoglobin after injecting ca.
      1.0 microL of ultradilute lysed red blood cells. The experimental results
      indicate that our proposed method has great potential for use in diagnosis and
      proteomics applications.

PMID- 16457611
TI  - Pre-extraction sample handling by automated frozen disruption significantly
      improves subsequent proteomic analyses.
AB  - Here we quantitatively characterize two common homogenization strategies in the
      analysis of tissue proteomes: classical manual homogenization (MH) and an
      automated frozen disruption (AFD) technique. In a variety of tissues, many
      proteins were more efficiently extracted, resolved and detected, with high
      reproducibility after AFD, amounting to as much as 2% of the total resolved
      proteome. The benefits of AFD over MH are 2-fold: (1) AFD yields a much more
      thorough homogenate than MH; and (2) as a deep frozen alternative, AFD maintains
      a level of biological complexity that is not retained during MH. Thus, AFD
      coupled with refined 2DE protocols and Sypro Ruby staining yields quantitative
      proteomic analyses.

PMID- 16457612
TI  - Structural-functional model of the mitotic chromosome.
AB  - In the present review the structural role of noncoding DNA, mechanisms of
      differential staining of mitotic chromosomes, and structural organization of
      different levels of DNA compactization are discussed. A structural-functional
      model of the mitotic chromosome is proposed based on the principle of
      discreteness of structural levels of DNA compactization.

PMID- 16457613
TI  - Role of biologically active sphingolipids in tumor growth.
AB  - This review highlights the literature on the effects of biologically active
      sphingolipids (sphingosine, ceramide, sphingomyelin, glucosylceramide,
      gangliosides GM1, GM2, GM3, GD3, etc.) on proliferation, apoptosis, metastases,
      and invasiveness of tumor cells and the putative role of sphingolipids in
      chemotherapy of malignant tumors.

PMID- 16457614
TI  - Identification of latent periodicity in amino acid sequences of protein families.
AB  - For detection of the latent periodicity of the protein families responsible for
      various biological functions, methods of information decomposition, cyclic
      profile alignment, and the method of noise decomposition have been used. The
      latent periodicity, being specific to a particular family, is recognized in 94 of
      110 analyzed protein families. Family specific periodicity was found for more
      than 70% of amino acid sequences in each of these families. Based on such
      sequences the characteristic profile of the latent periodicity has been deduced
      for each family. Possible relationship between the recognized latent periodicity,
      evolution of proteins, and their structural organization is discussed.

PMID- 16457615
TI  - Use of the Addressing Sequence of Yeast D-Lactate Dehydrogenase for Insertion of
      CYP11A1p into the Inner Membrane of Yeast Mitochondria.
AB  - Mammalian cytochrome P450scc (CYP11A1p) is a pseudointegral protein of the inner
      membrane of mitochondria with the active center exposed in the matrix. Upon
      import of the CYP11A1p precursor into yeast mitochondria, only a minor part was
      incorporated into the inner mitochondrial membrane and acquired catalytic
      activity (Kovaleva, I. E., Novikova, L. A., Nazarov, P. A., Grivennikov, S. I.,
      and Luzikov, V. N. (2003) Eur. J. Biochem., 270, 222-229). The present work is an
      attempt to increase the efficiency of this process by substitution of the
      inherent N-terminal presequence of CYP11A1p by the addressing signal of D-lactate
      dehydrogenase (D-LD) of the yeast Saccharomyces cerevisiae. D-LD is known to be
      inserted into the inner membrane of mitochondria through its transmembrane domain
      located close to the N-terminus of the polypeptide chain in such a way that the
      protein globule is exposed in the intermembrane space. The hybrid protein D-LD(1
      72)-mCYP11A1p synthesized in yeast cells was imported into yeast mitochondria,
      underwent processing, and was inserted into the inner membrane on the side of the
      intermembrane space. In the presence of adrenodoxin and adrenodoxin reductase,
      the hybrid protein exhibited cholesterol side-chain cleavage activity. Thus,
      CYP11A1p insertion into the inner membrane of mitochondria mediated by the D-LD
      topogenic signal resulted in the catalytically active mCYP11A1p domain in the
      hybrid protein.

PMID- 16457617
TI  - Amphenicol and macrolide derived antibiotics inhibit paraoxonase enzyme activity
      in human serum and human hepatoma cells (HepG2) in vitro.
AB  - Human serum paraoxonase (hPON1) was separately purified by ammonium sulfate
      precipitation and hydrophobic interaction chromatography. The in vitro effects of
      commonly used antibiotics, namely clarithromycin and chloramphenicol, on purified
      human serum paraoxonase enzyme activity (serum hPON1) and human hepatoma (HepG2)
      cell paraoxonase enzyme activity (liver hPON1) were determined. Serum hPON1 and
      liver hPON1 were determined using paraoxon as a substrate and IC(50) values of
      these drugs exhibiting inhibition effects were found from graphs of hydratase
      activity (%) by plotting concentration of the drugs. We determined that
      chloramphenicol and clarithromycin were effective inhibitors of serum hPON1.

PMID- 16457616
TI  - Specific features of changes in levels of endogenous respiration substrates in
      Saccharomyces cerevisiae cells at low temperature.
AB  - The rate of endogenous respiration of Saccharomyces cerevisiae cells incubated at
      0 degrees C under aerobic conditions in the absence of exogenous substrates
      decreased exponentially with a half-period of about 5 h when measured at 30
      degrees C. This was associated with an indirectly shown decrease in the level of
      oxaloacetate in the mitochondria in situ. The initial concentration of
      oxaloacetate significantly decreased the activity of succinate dehydrogenase. The
      rate of cell respiration in the presence of acetate and other exogenous
      substrates producing acetyl-CoA in mitochondria also decreased, whereas the
      respiration rate on succinate increased. These changes were accompanied by an at
      least threefold increase in the L-malate concentration in the cells within 24 h.
      It is suggested that the increase in the L-malate level in the cells and the
      concurrent decrease in the oxaloacetate level in the mitochondria should be
      associated with a deceleration at 0 degrees C of the transport of endogenous
      respiration substrates from the cytosol into the mitochondria. This deceleration
      is likely to be caused by a high Arrhenius activation energy specific for
      transporters. The physiological significance of L-malate in regulation of the S.
      cerevisiae cell respiration is discussed.

PMID- 16457618
TI  - Dimethyl- and monomethyloxyluciferins as analogs of the product of the
      bioluminescence reaction catalyzed by firefly luciferase.
AB  - The absorption and fluorescence spectra of dimethyloxyluciferin (DMOL) and
      monomethyloxyluciferin (MMOL) were studied at pH 3.0-12.0. In the range of pH 3.0
      8.0, the fluorescence spectrum of DMOL exhibits a maximum at lambda(em) = 639 nm.
      At higher pH values an additional emission maximum appears at lambda(em) = 500 nm
      (wavelength of excitation maximum lambda(ex) = 350 nm), which intensity increases
      with time. It is shown that this peak corresponds to the product of DMOL
      decomposition at pH > 8.0. The absorption spectra of MMOL were studied in the
      range of pH 6.0-9.0. At pH 8.0-9.0, the absorption spectrum of MMOL exhibits one
      peak at lambda(abs) = 440 nm. At pH 7.3-7.7, an additional band appears with
      maximum at lambda(abs) = 390 nm. At pH 6.0-7.0 two maxima are observed, at
      lambda(abs) = 375 and 440 nm. The fluorescence spectra of MMOL (pH 6.0-9.7,
      lambda(ex) = 440 or 375 nm) exhibit one maximum. It is shown that decomposition
      of DMOL and MMOL in aqueous solutions results in products of similar structure.
      DMOL and MMOL are rather stable at the pH optimum of luciferase. It is suggested
      that they can be used as fluorescent markers for investigation of the active site
      of the enzyme.

PMID- 16457619
TI  - Single step immobilized metal ion affinity precipitation/chromatography based
      procedures for purification of concanavalin A and Cajanus cajan mannose-specific
      lectin.
AB  - Concanavalin A and a mannose-specific lectin could be precipitated specifically
      from extracts of jack bean and Cajanus cajan seeds, respectively, using metal
      charged EGTA. Single step purification of the lectins was also possible using
      iminodiacetic acid-Sepharose charged with metal ions. Nondenaturing
      electrophoresis in polyacrylamide gel and that performed in presence of SDS
      ascertained homogeneity of the isolated lectins. The migration behavior of the
      purified lectins was comparable with those of the lectins purified using
      alternative procedures.

PMID- 16457620
TI  - Hydrogen peroxide produced inside mitochondria takes part in cell-to-cell
      transmission of apoptotic signal.
AB  - In monolayer of HeLa cells treated with tumor necrosis factor (TNF), apoptotic
      cells formed clusters indicating possible transmission of apoptotic signal via
      the culture media. To investigate this phenomenon, a simple method of enabling
      two cell cultures to interact has been employed. Two coverslips were placed side
      by side in a Petri dish, one coverslip covered with apoptogen-treated cells (the
      inducer) and another with non-treated cells (the recipient). TNF, staurosporine,
      or H2O2 treatment of the inducer cells is shown to initiate apoptosis on the
      recipient coverslip. This effect is increased by a catalase inhibitor
      aminotriazole and is arrested by addition of catalase or by pre-treatment of
      either the inducer or the recipient cells with nanomolar concentrations of
      mitochondria-targeted cationic antioxidant MitoQ (10-(6 
      ubiquinolyl)decyltriphenylphosphonium), which specifically arrests H2O2-induced
      apoptosis. The action of MitoQ is abolished by an uncoupler preventing
      accumulation of MitoQ in mitochondria. It is concluded that reactive oxygen
      species (ROS) produced by mitochondria in the apoptotic cells initiate the
      release of H2O2 from these cells. The H2O2 released is employed as a long
      distance cell suicide messenger. In processing of such a signal by the recipient
      cells, mitochondrial ROS production is also involved. It is suggested that the
      described phenomenon may be involved in expansion of the apoptotic region around
      a damaged part of the tissue during heart attack or stroke as well as in
      "organoptosis", i.e. disappearance of organs during ontogenesis.

PMID- 16457621
TI  - Periplasmic superoxide dismutase from Desulfovibrio desulfuricans 1388 is an iron
      protein.
AB  - It is shown that the genome of the sulfate-reducing bacterium Desulfovibrio
      desulfuricans 1388 contains a superoxide dismutase (SOD) gene (sod). The gene
      encodes an export signal peptide characteristic for periplasmic redox proteins.
      The amino acid sequence showed high homology with iron-containing SODs from other
      bacteria. Electrophoretically pure SOD was isolated from the periplasmic fraction
      of bacterial cells by FPLC chromatography. Like other Fe-SODs, D. desulfuricans
      1388 superoxide dismutase is inhibited by H2O2 and azide, but not by cyanide.

PMID- 16457622
TI  - Macrophage migration inhibitory factor: isolation from bovine brain.
AB  - The purification of macrophage migration inhibitory factor (MIF) from bovine
      brain cytosol and its partial characterization are reported. A rapid and
      relatively simple method for MIF isolation was developed based mainly on size
      exclusion chromatography on Toyopearl TSK polymer having a tendency to adsorb MIF
      as compared to elution of other proteins with similar molecular weights. The
      method gives a high yield of MIF (0.1 mg homogenous protein per g wet tissue).
      The retardation is conveniently utilized to achieve good separations of MIF from
      other proteins of similar molecular weights. The isolated protein was identified
      as MIF by SDS-electrophoresis, immunoblotting, sequencing of the N-terminal amino
      acid residues, and also by determination of keto-enol tautomerase activity that
      is characteristic of MIF with p-hydroxyphenylpyruvic acid as a substrate.

PMID- 16457623
TI  - Hydrolytic approach for production of deoxyribonucleoside- and ribonucleoside-5 
      monophosphates and enzymatic synthesis of their polyphosphates.
AB  - A new, simple, and ingenious method for enzymatic synthesis of deoxy- and
      ribonucleoside-5 -triphosphates (dNTP and NTP, respectively) has been developed.
      The method includes the following stages: hydrolysis of DNA with DNase and
      immobilized S1-nuclease, phosphorylation of the resulting deoxy- and
      ribonucleoside-5 -monophosphates (dNMP and NMP, respectively) with nucleotidyl
      kinase from Escherichia coli, and purification by chromatography of the
      synthesized dNTP and NTP. dNMP was phosphorylated using an ATP-regenerating
      system based on acetokinase from E. coli and lithium acetylphosphate.

PMID- 16457624
TI  - Interaction of native Bowman-Birk soybean protease inhibitor and its
      hydrophobized derivative with multilamellar vesicles of soybean phospholipids.
AB  - The interaction of native Bowman-Birk soybean protease inhibitor (BBI) and its
      hydrophobized derivative with multilamellar vesicles of various soybean
      phospholipids was investigated. Decrease in pH and introduction of negatively
      charged components to the lipid mixture increased BBI content in the protein
      lipid complex. This suggests a contribution of electrostatic forces in the
      protein-lipid interaction. Protein hydrophobization insignificantly influenced
      BBI binding to lipids. In the complex with lipids, both proteins (BBI and its
      hydrophobized derivative) retained high anti-chymotrypsin activity (75-100%),
      which was not influenced by the presence of the ionic detergent sodium
      deoxycholate.

PMID- 16457625
TI  - Analysis of benzo[a]pyrene deactivation mechanisms in rats.
AB  - The experimental data on the effects of a widespread carcinogen, benzo[a]pyrene
      (BP), on individual reactions of rats were treated using mathematical-statistical
      methods. The individual reactions were analyzed in dependence of doses and modes
      of administration (single or chronic). The analysis revealed a statistically
      significant correlation between life span and urinary content of (+/-)-trans-7,8
      dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-BP) in rats treated with BP. The
      calculated regression equations revealed that the individual sensitivity to
      carcinogen in case of the BP single administration to rats is mainly determined
      by efficiency of excretion of the BP active forms out of the organism, whereas
      after chronic BP administration it is determined by mechanisms of enzymatic
      deactivation of BP.

PMID- 16457626
TI  - Lipid-mediated inactivation of colicin E1 channels by calcium ions.
AB  - Based on the model of a toroidal protein-lipid pore, the effect of calcium ions
      on colicin E1 channel was predicted. In electrophysiological experiments Ca2+
      suppressed the activity of colicin E1 channels in membranes formed of
      diphytanoylphosphatidylglycerol, whereas no desorption of the protein occurred
      from the membrane surface. The effect of Ca2+ was not observed on membranes
      formed of diphytanoylphosphatidylcholine. Single-channel measurements revealed
      that Ca2+-induced reduction of the colicin-induced current across the negatively
      charged membrane was due to a decrease in the number of open colicin channels and
      not changes in their properties. In line with the toroidal model, the effect of
      Ca2+ on the colicin E1 channel-forming activity is explained by alteration of the
      membrane lipid curvature caused by electrostatic interaction of Ca2+ with
      negatively charged lipid head groups.

PMID- 16457628
TI  - Solid-phase synthesis in the twenty-first century.
AB  - Solid-phase synthesis is a powerful tool for achieving high-throughput chemistry.
      This review discusses recent diverse examples from my group: the solid-phase
      synthesis of unsymmetrical guanidines, polymer-supported versions of
      cyclooctadiene and 9-BBN, a triflate-like linker, the synthesis of tetrahydro
      beta-carbolines by the acyliminium Pictet-Spengler reaction, and a total
      synthesis of the antimycobacterial cyclic depsipeptide natural product kahalalide
      A.

PMID- 16457629
TI  - Solid-phase chemistry in the total synthesis of non-peptidic natural products.
AB  - Solid-phase chemistry, first introduced for peptide synthesis in the 1960's, has
      become an integral part of organic synthetic methodology. Presented herein is an
      overview of recent examples of the use of solid-phase in the preparation of non
      peptidic natural products and related compounds, encompassing on-resin total
      syntheses as well as the use of polymer-supported reagents in solution.

PMID- 16457630
TI  - Solid-phase synthesis of biologically interesting compounds containing hydroxamic
      acid moiety.
AB  - Chemical strategies developed for the solid-phase synthesis of hydroxamates are
      divided into four groups: (i) the traditional synthesis of hydroxamates via
      cleavage of resin-bound esters by hydroxylamine and its derivatives, (ii)
      introduction of hydroxamic acid moiety on the resin-bound precursor, (iii)
      transformation of polymer-supported hydroxylamine, attached to a solid supported
      linker either by oxygen (O-linking strategy) or by nitrogen (N-linking strategy),
      and (iv) synthesis of N-alkyl hydroxamates. The scope and limitation of
      individual approaches are discussed.

PMID- 16457631
TI  - Solid-phase organic synthesis (SPOS) of modulators of estrogenic and androgenic
      action.
AB  - Estrogens and androgens are key growing factors involved in a large series of
      disorders. Two main strategies are possible for controlling their undesirable
      agonist effects: (1) blocking their biosynthesis by using selective enzyme
      inhibitors, and (2) antagonizing their hormonal action on a receptor with an
      antiestrogen or an antiandrogen. In this review, we will briefly discuss the
      identification of a series of important therapeutic targets, through the study of
      steroidogenesis of potent estrogens, estrone and estradiol, and potent androgens,
      testosterone and dihydrotestosterone, as well as of their nuclear receptors. We
      will next review the solid-phase synthesis of steroidogenic enzyme (steroid
      sulfatase and 17beta-hydroxysteroid dehydrogenases) inhibitors and steroid
      (estrogen and androgen) receptor modulators, all being potential therapeutic
      agents for the treatment of hormone-sensitive diseases.

PMID- 16457632
TI  - Recent advances in the solid-phase combinatorial synthetic strategies for the
      benzodiazepine based privileged structures.
AB  - Benzodiazepine based heterocycles can be prepared efficiently on solid-support by
      employing different approaches. In this review, an effort has been made to
      highlight academic and industrial examples of combinatorial synthesis for this
      type of heterocycles published in the last decade. Therefore, it describes
      synthetic strategies for the generation of benzodiazepine privileged structures
      employing the corresponding resin-bound substrates. Further, the most relevant
      biological properties of these heterocycles have also been incorporated.

PMID- 16457633
TI  - Recent advances in the solid-phase combinatorial synthetic strategies for the
      quinoxaline, quinazoline and benzimidazole based privileged structures.
AB  - Quinoxaline, quinazoline and benzimidazole based templates have been synthesized
      on solid-support employing different methodologies. This review enlightens
      academic and industrial examples of combinatorial synthesis for this type of
      heterocycles that appeared in the literature in the last decade. Hence, some of
      the important synthetic strategies for the generation of quinoxaline, quinazoline
      and benzimidazole based privileged structures, and the important biological
      activities for these heterocycles have been highlighted. Further,
      benzothiadiazinone, thioxoquinazolinone, cinnoline and indazole are also examined
      in this review.

PMID- 16457635
TI  - The polymer-supported and combinatorial synthesis of beta-lactam compounds: an
      update.
AB  - Solid-phase organic synthesis (SPOS) has become an effective synthetic tool for
      the preparation of combinatorial libraries of non-oligomeric small molecules.
      Owing to their high efficacy and extremely safe toxicological profile, beta
      lactam antibiotics are the first choice for bacterial infectious diseases.
      Moreover, beta-lactam compounds have also showed other biological activities that
      include inhibition of prostate specific antigen, thrombin, human cytomegalovirus
      protein, human leukocyte elastase and cholesterol absorption. Thus, the
      application of combinatorial and related methodologies to the chemistry of the
      beta-lactam ring has been recognized as a very attractive challenge by different
      research groups around the world. This review covers the solid-phase and
      combinatorial chemistry related to mono-and multicyclic beta-lactam compounds
      that has been reported in the literature from 1999 to 2004.

PMID- 16457634
TI  - Recent advances in combinatorial chemistry applied to development of anti-HIV
      drugs.
AB  - A compilation of combinatorial chemistry techniques applied to anti-HIV drug
      development is presented in this review. This synthetic strategy together with
      high throughput screening assays has allowed the discovery and optimization of
      novel lead anti-HIV compounds.

PMID- 16457637
TI  - Recent developments in the design of orally bioavailable beta3-adrenergic
      receptor agonists.
AB  - The beta3-adrenergic receptor (beta3-AR) has been shown to mediate various
      pharmacological and physiological effects such as lipolysis, thermogenesis, and
      relaxation of the urinary bladder. Activation of the beta3-AR is thought to be a
      possible approach for the treatment of obesity, type 2 diabetes mellitus, and
      frequent urination. Therefore, the beta3-AR is recognized as an attractive target
      for drug discovery. On the other hand, activation of the beta1- or beta2-AR can
      cause undesirable side effects such as increased heart rate or muscle tremors.
      Consequently, a number of recent efforts in this field have been directed toward
      the design of selective agonists for the beta3-AR. This review summarizes recent
      advances in beta3-AR agonists with an emphasis on recent attempts to create
      potent, selective and orally bioavailable small-molecule agonists.

PMID- 16457636
TI  - Naturally occurring and synthetic imidazoles: their chemistry and their
      biological activities.
AB  - Imidazoles are an important class of heterocycles and include many substances of
      both biological and chemical interest. They are part of a large number of highly
      significant biomolecules such as the essential amino acid histidine and related
      compounds, biotin, and the imidazole alkaloids. Insertion of the imidazole
      nucleus is an important synthetic strategy in drug discovery. Imidazole drugs
      have broad applications in many areas of clinical medicine. The imidazoles are a
      class of antifungal azole derivatives and have a broad spectrum of activities
      both in vitro and in vivo. The imidazole moiety is also contained in many
      histaminergic ligands for histamine H1, H2, and H3 receptors. These are currently
      used as tools in pharmacological studies. The important therapeutic properties of
      imidazole related drugs have encouraged the medicinal chemists to synthesize and
      test a large number of novel molecules. Some of these have chemotherapeutic
      properties, such as for example several FTase inhibitors with an imidazole
      moiety. Imidazole derivatives have also been shown to have antibacterial activity
      and recently several P38 MAP Kinase inhibitors and 5-Lipoxygenase inhibitors
      containing the imidazole moiety have been synthesized. This review reports
      current progress in the area of new biologically active imidazoles and recently
      discovered naturally occurring imidazole.

PMID- 16457638
TI  - Bacterial symbionts: prospects for the sustainable production of invertebrate
      derived pharmaceuticals.
AB  - Invertebrate animals, such as sponges, tunicates and bryozoans, are among the
      most important sources of biomedically relevant natural products. However, as
      these animals generally contain only low quantities of the compounds, further
      pharmacological development is in most cases difficult. There is increasing
      evidence that many metabolites, in particular polyketides and nonribosomally
      synthesized peptides, are not produced by the animals themselves but by
      associated bacterial symbionts. This symbiont hypothesis currently attracts
      considerable interest, since it implicates that animal-independent production
      systems based on bacterial fermentation processes could be created. This review
      gives an overview about recent developments in the research on natural product
      symbiosis. Different techniques will be discussed that have been employed to
      pinpoint the actual producer. Since bacterial symbionts are highly fastidious and
      have been generally resistant to cultivation attempts, emphasis will be laid on
      culture-independent strategies, such as cell separation approaches and the
      cloning of biosynthetic genes. These strategies have provided insights into
      possible sources of several natural products, e.g. the bryostatins, pederin, the
      onnamides, swinholide A and theopalauamide. Finally, potential techniques for the
      generation of renewable supplies of symbiont-derived drug candidates will be
      discussed. Cultivation approaches and the heterologous expression of cloned
      biosynthesis genes from uncultured symbionts could in future provide access to
      several important marine drug candidates, including bryostatin 1, halichondrin or
      ET-743.

PMID- 16457639
TI  - Heptahelical and other G-protein-coupled receptors (GPCRs) signaling.
AB  - Heptahelical receptors are coupled to heterotrimeric GTP-binding proteins (G
      proteins) which transduce most signals through their alpha and betagamma subunits
      to effectors, enzymes and ion channels. Of the 367 heptahelical receptors for
      endogenous ligands, about 330 are potential targets for drug discovery with
      agonist, antagonist or inverse agonist properties. The term G-protein-coupled
      receptors (GPCRs) is a broader functional definition rather than a structural one
      referring to heptahelical receptors specifically. Non-heptahelical putative GPCRs
      include some transmembrane receptors with tyrosine-kinase activity on their
      cytosolic endings (EGF, insulin and IGF-1 receptors), other transmembrane
      receptors (mannose-6-phosphate/IGF-2 receptor and integrin-associated protein IAP
      or CD47), and some receptors belonging to the class of
      glycosylphosphatidylinositol (GPI)-anchored proteins and located on the outer
      face of the plasma membrane. Also, activators of G-protein signaling (AGS)
      proteins that regulate vesicular trafficking activate heterotrimeric G-proteins
      in the Golgi independently of receptor activation. Main effectors activated
      through their direct interactions with alpha subunits or betagamma dimers of
      heterotrimeric G-proteins include adenylylcyclases, cGMP-phosphodiesterase,
      phospholipases Cbeta, phosphoinositide 3-kinase gamma, Ca(V2) calcium channels,
      GIRK/Kir3 potassium channels, and guanine nucleotide exchange factors RasGEF and
      RhoGEF leading to small G-proteins and MAP-kinases activation. Current signaling
      cascades leading to final cell responses are depicted.

PMID- 16457640
TI  - Privileged structures as leads in medicinal chemistry.
AB  - Among the strategies that can lead to the discovery of new drugs, the
      identification and use of privileged structures, molecular fragments that are
      able to interact with more than one target, gained particular attention, in an
      attempt to find new drugs in a shorter time with respect to other strategies.
      These structures, that have been identified mainly by empirical observations, can
      target only a given protein family, or can be able to interact with more,
      unrelated targets. This review deals with structures not covered in recent papers
      on this topic, and emphasizes the importance of understanding the structure
      target relationships, that confer the privileged status.

PMID- 16457642
TI  - Sol-gel chemistry in medicinal science.
AB  - The sol-gel process is an inorganic polymerization process taking place in mild
      conditions, allowing the association of mineral phases with organic or biological
      systems. The possibility to immobilize drugs, enzymes, antibodies and even whole
      cells without loss of their biological activity led to the development of
      diagnostic tools, drug delivery carriers as well as new hosts for artificial
      organ design. These systems take profit from the wide variety of chemical
      compositions, dimensions and forms that can be achieved via sol-gel chemistry.
      Recent advances involve multi-functional "smart" devices combining
      biocompatibility, biological activity and stimuli-responsive materials. The
      design of such novel devices with significant added value when compared to
      current products is probably a key factor when foreseeing industrial developments
      of sol-gel materials in medicinal science.

PMID- 16457641
TI  - Comparative studies of the antioxidant effects of cis- and trans-resveratrol.
AB  - Resveratrol (3,4',5-trihydroxystilbene, RESV) is a natural phenolic compound that
      exists as cis and trans isomers [c-RESV or (Z)-RESV and t-RESV or (E)-RESV,
      respectively]. t-RESV is a natural component of Vitis vinifera L. (Vitaceae),
      abundant in the skin of grapes (but not in the flesh) and in the leaf epidermis,
      and present in wines, especially red wines. In in vitro, ex vivo and in vivo
      experiments t-RESV exhibits a number of biological activities, including anti
      inflammatory and anticarcinogenic properties. RESV also exists in wines as a cis
      isomer, which (unlike t-RESV) is not currently available commercially; as a
      result, little is known about this isomer's pharmacological activity. In this
      review, I will focus on the few comparative studies of the antioxidant effects of
      the two RESV isomers in different experimental models.

PMID- 16457643
TI  - Voglibose (Basen, AO-128), one of the most important alpha-glucosidase
      inhibitors.
AB  - The number of people with diabetes is expected to rise from the current estimated
      150 million to 220 million in 2010 and 300 million in 2025, and 90% is Type 2
      diabetes or non-insulin dependent diabetes mellitus (NIDDM). Voglibose, one of
      the most important alpha-glucosidase inhibitors, delays the digestion and
      absorption of carbohydrates, thereby inhibiting postprandial hyperglycemia and
      hyperinsulinemia, and is the aid in the treatment of diabetes. In this paper,
      properties and the preparation of voglibose are reviewed.

PMID- 16457647
TI  - Gene therapy of cancer based on interleukin 12.
AB  - Tumor formation and growth depends mainly on the inability of the organism to
      elicit a potent immune response, and on the formation of new blood vessels that
      enable tumor nutrition. Interleukin-12 (IL-12) therapy can target both processes.
      And IL-12-based gene therapy may restrict IL-12 production to the relevant site
      in order to obtain enhanced antitumor activity and reduced toxicity. In the
      clinical setting, IL-12 gene transfer can be used either to improve the
      pharmacokinetic/pharmacodynamic profile of the cytokine, to transduce dendritic
      cells or to enhance the efficiency of antitumor vaccination. It can also
      synergize with other procedures involving the simultaneous transfer of other
      transgenes or non-gene based strategies. The strong anti-tumoral power shown in
      many different animal models has not been found in early clinical trials in which
      cancer patients were treated by peritumoral injections of autologous fibroblasts
      producing IL-12, intratumoral injections of an adenoviral vector encoding human
      IL-12 genes, or intratumoral injection of autologous dendritic cells transduced
      ex vivo with this same adenoviral vector. However, these trials have set the
      proof-of-concept that local production of IL-12 inside a tumor can stimulate
      tumor infiltration by effector immune cells and that in some cases it is followed
      by tumor regression. From the many questions that arise after these disappointing
      results the most relevant concerns the duration and intensity of transgene
      expression and the capability to monitor this topics in vivo. New vectors that
      might achieve regulated, long-term production of this cytokine might have better
      results and merit clinical testing.

PMID- 16457648
TI  - Prospects and limitations of T cell receptor gene therapy.
AB  - Adoptive transfer of antigen-specific T cells is an attractive means to provide
      cancer patients with immune cells of a desired specificity and the efficacy of
      such adoptive transfers has been demonstrated in several clinical trials. Because
      the T cell receptor is the single specificity-determining molecule in T cell
      function, adoptive transfer of TCR genes into patient T cells may be used as an
      alternative approach for the transfer of tumor-specific T cell immunity. On
      theoretical grounds, TCR gene therapy has two substantial advantages over
      conventional cellular transfer, as it can circumvent the demanding process of in
      vitro generation of large numbers of specific immune cells and it allows the use
      of a set of particularly effective TCR genes in large patient groups. Conversely,
      TCR gene therapy may be associated with a number of specific problems that are
      not confronted during classical cellular therapy. Here we review our current
      understanding of the potential and possible problems of TCR gene therapy, as
      based on in vitro experiments and mouse model systems. Furthermore, we discuss
      the prospects of clinical application of this gene therapy approach, and the
      possible barriers on the route towards clinical use.

PMID- 16457646
TI  - Gene therapy for pituitary tumors.
AB  - Pituitary tumors are the most common primary intracranial neoplasms. Although
      most pituitary tumors are considered typically benign, others can cause severe
      and progressive disease. The principal aims of pituitary tumor treatment are the
      elimination or reduction of the tumor mass, normalization of hormone secretion
      and preservation of remaining pituitary function. In spite of major advances in
      the therapy of pituitary tumors, for some of the most difficult tumors, current
      therapies that include medical, surgical and radiotherapeutic methods are often
      unsatisfactory and there is a need to develop new treatment strategies. Gene
      therapy, which uses nucleic acids as drugs, has emerged as an attractive
      therapeutic option for the treatment of pituitary tumors that do not respond to
      classical treatment strategies if the patients become intolerant to the therapy.
      The development of animal models for pituitary tumors and hormone hypersecretion
      has proven to be critical for the implementation of novel treatment strategies
      and gene therapy approaches. Preclinical trials using several gene therapy
      approaches for the treatment of anterior pituitary diseases have been
      successfully implemented. Several issues need to be addressed before clinical
      implementation becomes a reality, including the development of more effective and
      safer viral vectors, uncovering novel therapeutic targets and development of
      targeted expression of therapeutic transgenes. With the development of efficient
      gene delivery vectors allowing long-term transgene expression with minimal
      toxicity, gene therapy will become one of the most promising approaches for
      treating pituitary adenomas.

PMID- 16457649
TI  - Adenovirus-based cancer gene therapy.
AB  - Over the past decade, adenovirus (Ad)-based vectors have been used extensively in
      the context of cancer gene therapy. Two basic strategies have been pursued for
      the use of Ad vectors in cancer gene therapy: 1) approaches aimed at direct tumor
      cell killing through delivery of replicating oncolytic viruses or non-replicating
      vectors encoding tumor suppressor genes, suicide genes or anti-angiogenic genes,
      and 2) immunotherapeutic approaches aimed at inducing host anti-tumor immune
      responses that can destroy tumor cells at both primary and metastatic locations.
      Both strategies offer the potential of selective tumor cell destruction without
      damage to normal tissues. Extensive pre-clinical and clinical studies have been
      conducted based on these strategies. Encouraging results have been obtained but
      robust clinical efficacy remains elusive. Several obstacles limiting the
      therapeutic activity of Ad vectors have been encountered, including efficiency of
      tumor cell transduction and inhibition of efficacy by anti-Ad host immune
      responses. However, expanding knowledge in the areas of Ad biology and tumor
      biology continues to lead to increasingly sophisticated approaches to address
      these issues. A review of various Ad-based cancer gene therapy approaches and
      recent progress in the area are presented herein.

PMID- 16457650
TI  - Applications of molecular imaging in cancer gene therapy.
AB  - Gene-based therapy is a promising and flexible therapeutic approach to manage
      diverse types of cancer. The lack of convincing therapeutic success of current
      gene therapy protocols in part, can be attributed to the inability to monitor
      gene expression at the targeted site in the living subject. Linking molecular
      imaging to gene therapy will enable real-time assessment of the therapeutic
      process and the refinement of treatment protocols. This review will cover two
      common imaging modalities, positron emission tomography (PET) and bioluminescence
      imaging (BLI), used in pre-clinical and clinical gene therapy applications.
      Strategies to develop more specific and robust cancer gene therapy and imaging
      approaches will be discussed. Coupling PET to gene therapy of cancer has already
      been implemented in several clinical studies. This approach would help to improve
      the efficacy and safety of future gene therapy clinical trials.

PMID- 16457651
TI  - Genetically modified dendritic cells for cancer immunotherapy.
AB  - The ability to grow and differentiate dendritic cells (DC) ex vivo has allowed
      their genetic manipulation to enhance immune activation against tumor antigens.
      Gene engineering of DC can be achieved with a variety of physical methods and
      using different viral vectors. RNA or DNA transfection, either alone (naked),
      coated with liposomes or using electroporation or gene guns leads to T cell
      activation while transgene expression is frequently undetectable. Adenoviral and
      retroviral vectors have proven to be highly efficient in DC genetic modification,
      and have been widely used in preclinical models. Other vectors like lentivirus,
      poxvirus, herpes virus and adeno-associated virus (AAV) can also lead to foreign
      transgene expression in DC leading to immune cell activation. DC have been
      genetically engineered to provide constitutive and high level of tumor antigen
      expression or to introduce genes that further enhance their immune stimulatory
      ability. The promising results from preclinical animal models and from in vitro
      human immune cell culture systems have provided a strong rationale to initiate
      pilot clinical trials. Recently published or communicated clinical experiences
      and ongoing trials have used defined tumor antigen RNA transfection for prostate
      carcinoma and melanoma, liposome-encoated DNA transfection for breast or
      pancreatic cancer, adenoviral vector tumor antigen gene modification for melanoma
      and small cell lung cancer, and poxvirus-mediated expression of costimulatory
      molecules for colon carcinoma. These preliminary experiences suggest that
      genetically modified DC can safely induce T cell responses but few clinical
      responses.

PMID- 16457645
TI  - Gene therapy and targeted toxins for glioma.
AB  - The most common primary brain tumor in adults is glioblastoma. These tumors are
      highly invasive and aggressive with a mean survival time of nine to twelve months
      from diagnosis to death. Current treatment modalities are unable to significantly
      prolong survival in patients diagnosed with glioblastoma. As such, glioma is an
      attractive target for developing novel therapeutic approaches utilizing gene
      therapy. This review will examine the available preclinical models for glioma
      including xenographs, syngeneic and genetic models. Several promising therapeutic
      targets are currently being pursued in pre-clinical investigations. These targets
      will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted
      toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory
      approaches. Preclinical gene therapy paradigms aim to determine which strategies
      will provide rapid tumor regression and long-term protection from recurrence.
      While a wide range of potential targets are being investigated preclinically,
      only the most efficacious are further transitioned into clinical trial paradigms.
      Clinical trials reported to date are summarized including results from
      conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene
      targeting approaches. Clinical trial results have not been as robust as
      preclinical models predicted, this could be due to the limitations of the GBM
      models employed. Once this is addressed, and we develop effective gene therapies
      in models that better replicate the clinical scenario, gene therapy will provide
      a powerful approach to treat and manage brain tumors.

PMID- 16457653
TI  - Targeted gene therapy for ovarian cancer.
AB  - Despite advances in therapy, advanced ovarian cancer maintains a dismal overall
      survival of 15-30%. Thus, the need for novel therapeutic modalities exists. Gene
      therapy represents one such approach and the purpose of this review is to present
      a logical rationale for the investigation of gene therapy for the treatment of
      ovarian cancer. The different strategies of gene therapy (molecular chemotherapy
      (prodrugs), mutation compensation, immunotherapy approaches, altered drug
      sensitivity, and virotherapy) for cancer treatment are discussed separately with
      attention to investigations with clinical applicability. Furthermore, the
      different viral vectors utilized for improvements in targeted therapy are
      presented. The advancements, discovery, and shortcomings are reviewed which lend
      itself to future directions. These future directions involve coxsackie-adenovirus
      receptor (CAR) independent pathways to improve infectivity and specificity to
      ovarian tumor cells, the potential of utilizing gene therapy as an imaging
      modality in detecting cancer, and incorporating the recently described technique
      of RNA interference. Due to the advancements in detection and targeting of
      ovarian cancer, coupled with the containment to the intraperitoneal cavity, gene
      therapy remains a promising treatment modality for ovarian cancer.

PMID- 16457652
TI  - Nonviral vectors for cancer gene therapy: prospects for integrating vectors and
      combination therapies.
AB  - Gene therapy has the potential to improve the clinical outcome of many cancers by
      transferring therapeutic genes into tumor cells or normal host tissue. Gene
      transfer into tumor cells or tumor-associated stroma is being employed to induce
      tumor cell death, stimulate anti-tumor immune response, inhibit angiogenesis, and
      control tumor cell growth. Viral vectors have been used to achieve this proof of
      principle in animal models and, in select cases, in human clinical trials.
      Nevertheless, there has been considerable interest in developing nonviral vectors
      for cancer gene therapy. Nonviral vectors are simpler, more amenable to large
      scale manufacture, and potentially safer for clinical use. Nonviral vectors were
      once limited by low gene transfer efficiency and transient or steadily declining
      gene expression. However, recent improvements in plasmid-based vectors and
      delivery methods are showing promise in circumventing these obstacles. This
      article reviews the current status of nonviral cancer gene therapy, with an
      emphasis on combination strategies, long-term gene transfer using transposons and
      bacteriophage integrases, and future directions.

PMID- 16457654
TI  - Beyond oncolytic virotherapy: replication-competent retrovirus vectors for
      selective and stable transduction of tumors.
AB  - As cancer gene therapy employing replication-defective vectors has met with
      limited clinical success, there is renewed interest in using replication
      competent viruses for oncolytic virotherapy. In preclinical and clinical studies,
      various attenuated vaccine strains and engineered virus vectors are currently
      being tested for their ability to achieve tumor-selective cell killing. However,
      significant improvements are still required in tumor selectivity, cytolytic
      potency, and modulating immune responses to achieve anti-tumor effects without
      prematurely terminating virus spread. Recently, we have developed murine leukemia
      virus (MLV)-based replication-competent retrovirus (RCR) vectors for highly
      efficient, selective, and persistent gene transfer to cancer cells, and found
      that such vectors may offer significant advantages as oncolytic agents. In a
      variety of preclinical models, RCR vectors can achieve efficient and persistent
      gene delivery as the virus replicates throughout an entire tumor mass after
      inoculation with initial multiplicities of infection as low as 0.001. When
      engineered to deliver suicide genes, RCR vectors achieve highly efficient and
      synchronized cell killing triggered by pro-drug administration, both in culture
      and in tumor models in vivo. Further strategies are being explored to enhance the
      packaging capacity, efficiency, and specificity of this vector system through the
      development of semi-replicative RCR vectors, adenovirus-RCR hybrids, and
      incorporation of tumor targeting mechanisms via modification of binding tropism
      and transcriptional regulation. In addition, the ability of these vectors to
      achieve stable transgene expression in infected tumor cells may allow therapeutic
      applications that move beyond oncolysis per se.

PMID- 16457655
TI  - Bio-functional inorganic materials: an attractive branch of gene-based nano
      medicine delivery for 21st century.
AB  - Treatment of a physiological disorder in the genetic level (gene therapy) and
      induction of a specific immunity by means of a genetic material (genetic
      vaccination), are considered two revolutionary approaches for clinical medicine.
      The implementation strategies for these basic concepts demand a vehicle for
      nucleic acid delivery. Viral delivery systems, although highly efficient, possess
      severe limitations in terms of life safety and thus non-viral synthetic systems
      have become increasingly desirable. Intensive efforts for the last 3 decades
      enabled the development of a lot of synthetic devices, most of which belong to
      cationic lipids, peptides and other polymers, but comparatively little attention
      was paid to inorganic materials. This is the first article aimed at reviewing the
      dramatic progress of non-viral gene delivery research focusing on the functional
      inorganic materials. Both biodegradable and non-biodegradable inorganic particles
      have been fabricated in the nano-scale with the attributes of binding DNA,
      internalizing across the plasma membrane and finally releasing it in the
      cytoplasm for final expression of a protein. Some in vivo trials also brought
      highly satisfactory results demonstrating their potential applications in the
      clinical medicine.

PMID- 16457657
TI  - Tumour gene therapy monitoring using magnetic resonance imaging and spectroscopy.
AB  - Recent progress in gene therapy has increased the need for non-invasive imaging
      methods that would allow early diagnosis of successful treatment. Magnetic
      resonance methods, magnetic resonance imaging (MRI) and spectroscopy (MRS), have
      shown great promise to achieve this goal. The current mini-review describes
      recent advances in experimental MRI and MRS to detect individual treatment steps
      in gene therapy of tumours from gene transfection to therapy response.
      Limitations of the current techniques are also discussed.

PMID- 16457656
TI  - Gene therapy in systemic lupus erythematosus.
AB  - Despite the fact that the etiopathogenesis of systemic lupus erythematosus is
      largely unknown, key steps in the pathophysiology of the disease have been
      recognized and targeted using gene therapy techniques. In animal models of lupus,
      gene transfer has been used to block the action of pro-inflammatory cytokines and
      co-stimulatory molecules leading to clinical improvement. In humans, ex vivo
      experiments have shown the feasibility of gene transfer in live T cells and its
      potential for restoring normal phenotype in T cells from patients with lupus.
      Still in experimental phase, gene therapy in lupus promises to correct the
      aberrant immunological response without the numerous side-effects of the
      currently used immunosuppressant medications.

PMID- 16457659
TI  - Dispossessed of possessives? Is it PC? In this issue: more Keystone, Chiari
      strabismus, dyslexia from amblyopia, eso insertions, Duane's complexities, Golden
      Hirschberg CLRT photogrammetry.

PMID- 16457660
TI  - Chiari 1 malformation presenting as strabismus.
AB  - INTRODUCTION: Strabismus has been previously reported as a rare presenting
      feature of the Type 1 Chiari malformation. CASE REPORTS: We report a case series
      of twelve patients with Chiari 1 malformations with either strabismus or diplopia
      as part of their initial presentation. Ten patients had diplopia at the time of
      presentation, while 2 young children (ages 2 and 6) presented with esotropia
      without complaints of diplopia. Of the 10 patients with diplopia, 7 were
      constantly or frequently tropic while 3 had symptomatic phorias. One or more
      unusual features of the strabismus led to further investigations and the
      diagnosis of Chiari in these patients. The most common oculomotor disturbance was
      a comitant esotropia. Most patients were managed with prism glasses. One patient
      had strabismus surgery as primary treatment with early orthotropia. Three
      patients underwent neurosurgical decompression, with minimal improvement of their
      strabismus; one of these underwent subsequent successful strabismus surgery.
      CONCLUSIONS: Chiari 1 malformation may present with strabismus or diplopia as the
      major finding. Associated neurological features may be nonspecific (e.g.,
      headache), subtle (e.g., gaze-evoked nystagmus), or delayed. Although
      neurosurgery may be required in some cases, primary strabismus management
      (surgical or prismatic correction) can be successful, particularly when
      strabismus is the lone (or sole specific) finding.

PMID- 16457661
TI  - The prevalence of specific reading disability in an amblyopic population. A
      preliminary report.
AB  - PURPOSE: To investigate the prevalence of specific reading disability in children
      with functional amblyopia and to explore the relationship between the two.
      METHODS: In this prospective study, 20 consecutive children, aged 6 to 15 years
      (mean 8 +/-1.99 years), and diagnosed with amblyopia underwent a vision and
      reading assessment. The orthoptic examination included the assessment of
      participants' visual acuity, ocular motility and binocular functions. Specific
      reading disability was diagnosed using the Wide Range Achievement Test (WRAT III
      Reading Subtest). Intelligence, phonological awareness, rapid automatized naming
      (RAN), and the ability to read pseudo or nonsense words was also assessed using
      various psycho-linguistic reading tests. RESULTS: The prevalence of specific
      reading disability in this small series of amblyopic children was found to be 5%
      (n=1/20). This was even less than that reported in the local Victoria general
      population (16%). The type of amblyopia appeared related to phonological
      awareness (p=0.018) and decoding words (p=0.024), those with anisometropic
      amblyopia performing significantly better on these tasks than the strabismic
      amblyopes. The presence of binocular vision functions was also related to
      decoding words; those with binocular single vision performed better than those
      with suppression and lacking single binocular vision (p=0.007). Generally,
      amblyopic children also showed a lower RAN score when compared to phonological
      awareness score. There was no statistically significant difference for the
      severity of amblyopia (p=>0.05). CONCLUSIONS: In this very small pilot series,
      reading disorders were relatively rare in children with amblyopia. However,
      strabismic amblyopia and presence of suppression may have an adverse effect on
      phonological skills. In addition, amblyopia may be associated with a deficit in
      RAN. Further research is needed and planned to gain a better understanding about
      the relationship between amblyopia and reading ability.

PMID- 16457662
TI  - Confirmed: there is no correlation between the insertional distance between the
      nasal limbus and the insertion of the medial rectus muscle--and the size of the
      strabismus angle in infantile esotropia.
AB  - INTRODUCTION: Historical systems of measuring the amount of surgical recession of
      the medial rectus muscles appropriate to be performed for a given size of angle
      of infantile esotropia, based upon relative recession measurement from the limbus
      might have proven to be better than relative recession measurement from the
      insertion--if a positive correlation were found between the size of the angle of
      the esodeviation and the distance between the insertion of the medial rectus and
      the nasal limbus. A search of the scientific literature since 1966 as listed in
      PubMed (National Library of Medicine, formerly Index Medicus) did not reveal any
      additional confirmatory study of this type in PubMed. We therefore undertook to
      perform such a study. METHODS: Using standard strabismus calipers, at surgery for
      esotropia, intraoperative measurements were made of the insertional distance (in
      mm between the most nasal point of the clear cornea and, following standard
      surgical excision of the muscle from the globe, the anterior insertional ridge of
      the medial rectus muscle of the eye) in a series of 104 consecutive infantile
      esotropes operated by the author between 1987 and 1991. These data were then
      graphically plotted as the ordinate with the abscissa defined as the size of the
      angle of the esotropia measured with the prism alternate cover test the day prior
      to surgery. RESULTS: No correlation was found between the medial rectus muscle
      insertional distance and the size of the preoperative esodeviation in prism
      diopters, correlation coefficient r=0.14, p=0.078. DISCUSSION OF RESULTS: In this
      large series, the lack of a correlation has credibility as it fails to achieve
      conventional limits of a "statistical significance" of the difference.
      CONCLUSION: The lack of correlation between the size of the deviation and the
      insertional distance offers support for the widespread acceptance and use of the
      alternative, the dose-response curves based on the mm of recession measured from
      the anterior ridge of the medial rectus muscle insertion.

PMID- 16457663
TI  - Electro-oculography of smooth pursuit and optokinetic nystagmus eye movements in
      type I Duane's retraction syndrome.
AB  - INTRODUCTION: These two eye movements have not been previously studied in this
      condition by this method. METHODS: Five cases were studied. Both visual acuity
      and eye examination of anterior and posterior segments were normal. A Nicolet
      Nystar Plus system with chloride silver electrodes was used to record the EOG.
      RESULTS: Of the two systems under study, the smooth pursuit system showed the
      most relevant anomalies, both in the Duane's eye and in the apparently healthy
      eye. No correlation was found between the pursuit and optokinetic nystagmus
      disorders. In some cases, more significant abnormalities were observed in the
      clinically normal eye. CONCLUSIONS: The results clearly demonstrated a
      significant impairment of the pursuit system. This suggests that this motor
      disorder is not exclusively caused by hypoplasia or aplasia of the nucleus of the
      abducens nerve (VIth cranial nerve). These abnormalities might be related to a
      poor development of the rhombencephalon since both supramotor nuclei as well as
      the pathways of this system arise from this region of the embryonic brain. In the
      particular case of OKN, the supramotor nuclei have a different origin. Therefore,
      these systems might be affected differently.

PMID- 16457664
TI  - Individual case photogrammetric calibration of the Hirschberg Ratio (HR) for
      corneal light reflection test strabometry.
AB  - PURPOSE: The HR (prism diopters [PD] per mm of corneal light reflection test
      [CLRT] asymmetry for strabometry) varies in humans from 14 to 24 PD/mm, but is
      totally unpredictable. Photo(grammetric) HR calibration in (of) each case
      facilitates acceptable strabometry precision and accuracy. METHOD: Take 3 flash
      photos of the patient with both the preferred eye and then the deviating eye
      fixating straight ahead and then again with the deviation eye fixing at (+/-5-10
      PD) the strabismic angle on a metric rule (stick) one meter away from the camera
      lens (where 1 cm = 1 PD). RESULTS: On these 3 photos, make four precise
      measurements of the position of the CLR with reference to the limbus: In the
      deviating eye fixing straight ahead and fixating at the angle of deviation.
      Divide the mm difference in location into the change in the angle of fixation to
      determine the HR for this patient at this angle. Then determine the CLR position
      in both the deviating eye and the fixing eye in the straight ahead primary
      position picture. Apply the calculated calibrated HR to the asymmetry of the CLRs
      in primary position to determine the true strabismic deviation. CONCLUSIONS: This
      imaging method insures accurate Hirschberg CLRT strabometry in each case,
      determining the deviation in "free space", under conditions of normal binocular
      viewing, uncontaminated by the artifacts or inaccuracies of other conventional
      strabometric methods or devices. So performed, the Hirschberg CLRT is the gold
      standard of strabometry.

PMID- 16457666
TI  - Prevalence of symptoms associated with temporomandibular disorders in a Turkish
      population.
AB  - Despite numerous studies having been published, the epidemiology of
      temporomandibular disorders remains uncertain and controversial. The aim of this
      study was to estimate the prevalence and distribution of symptoms commonly
      associated with such disorders among a sample of adults in Istanbul, Turkey. A
      total of 1253 individuals aged 18 years were identified by using a random-digit
      dialing technique. They were asked standard questions about joint and jaw muscle
      pain, jaw opening, and joint sounds. Additional questions on tooth grinding and
      clenching, sleep patterns, and treatment-seeking behaviour were posed. Jaw pain
      was reported by 31% of the population. Women were more likely, than men, to
      respond positively to the questions concerning jaw pain. No gender- and age
      related differences in prevalence of difficulty opening, clicking, tooth
      grinding/clenching and being poorly rested were found.

PMID- 16457665
TI  - Wild-type and mutant ferroportins do not form oligomers in transfected cells.
AB  - Ferroportin [FPN; Slc40a1 (solute carrier family 40, member 1)] is a
      transmembrane iron export protein expressed in macrophages and duodenal
      enterocytes. Heterozygous mutations in the FPN gene result in an autosomal
      dominant form of iron overload disorder, type-4 haemochromatosis. FPN mutants
      either have a normal iron export activity but have lost their ability to bind
      hepcidin, or are defective in their iron export function. The mutant protein has
      been suggested to act as a dominant negative over the wt (wild-type) protein by
      multimer formation. Using transiently transfected human epithelial cell lines
      expressing mouse FPN modified by the addition of a haemagglutinin or c-Myc
      epitope at the C-terminus, we show that the wtFPN is found at the plasma membrane
      and in Rab5-containing endosomes, as are the D157G and Q182H mutants. However,
      the delV162 mutant is mostly intracellular in HK2 cells (human kidney-2 cells)
      and partially addressed at the cell surface in HEK-293 cells (human embryonic
      kidney 293 cells). In both cell types, it is partially associated with the
      endoplasmic reticulum and with Rab5-positive vesicles. However, this mutant is
      complex-glycosylated like the wt protein. D157G and G323V mutants have a
      defective iron export capacity as judged by their inability to deplete the
      intracellular ferritin content, whereas Q182H and delV162 have normal iron export
      function and probably have lost their capacity to bind hepcidin. In co
      transfection experiments, the delV162 mutant does not co-localize with the wtFPN,
      does not prevent its normal targeting to the plasma membrane and cannot be
      immunoprecipitated in the same complex, arguing against the formation of FPN
      hetero-oligomers.

PMID- 16457667
TI  - Individual difference in the number of chewing strokes and its determinant
      factors.
AB  - This study was carried out to clarify the distribution and individual variation
      of the number of chewing strokes before last swallowing (NCS), as well as to
      assess the factors that affect NCS, when dentulous adults masticate the same type
      of food. NCS was measured in 75 dentulous adults using gummy candies.
      Measurements were repeated five times to obtain the average and variation.
      Moreover, the correlation of NCS with various physiological factors (lateral
      width and vertical distance of chewing loop, angle of opening and closing path,
      opening and closing time, occlusal time, masticatory performance, number of
      occlusal contact points, occlusal contact area, occlusal force, flow rate of
      whole saliva and viscosity of whole saliva) and 28 personality factors were
      analysed by both of the single variate analysis and the multivariate analysis.
      The results showed that the average NCS was 41.0 +/- 16.0, and the coefficient of
      variation was 0.090 +/- 0.040. Additionally, the correlation between NCS and each
      factor was investigated, and found that any of these factors did not function as
      a single determinant for NCS. Following, determinant factors were further
      examined by the stepwise method of linear multiple regression analysis. From
      these analysis we found that when opening and closing time and four personality
      factors were combined, they were significantly involved in determining NCS (P <
      0.01). Therefore, we conclude that individual NCS until last swallowing is not
      determined by a sole, specific physiological factor but is affected by multiple
      factors including personality.

PMID- 16457668
TI  - The influence of age and dental status on elevator and depressor muscle activity.
AB  - The objective of this study was to determine whether the muscle activity at
      various mandibular positions is affected by age and dental status. Thirty
      edentulous subjects (E), 20 young dentate individuals (G1) and 20 older dentate
      individuals (G2) participated in this study. Surface electromyographic (EMG)
      recordings were obtained from the anterior temporal (T), masseter (M) and
      depressor muscles (D). Muscle activity was recorded during maximal voluntary
      contraction (MVC), maximal opening (O(max)) and in six different mandibular
      positions. One way anova and the Bonferroni tests were used to determine the
      differences between groups. Significant differences between the three tested
      groups were found at MVC and O(max) for all examined muscles (P < 0.001). The
      differences in muscle activity in dentate subjects of different age were found in
      protrusion for depressor muscles (P < 0.05) and in lateral excursive positions
      for the working side temporal (P < 0.05) and non-working side masseter and
      depressor muscle (P < 0.05). There was a significant effect regarding the
      presence of natural teeth or complete dentures in protrusion and maximal
      protrusion for all muscles (P < 0.05) and in lateral excursive positions for non
      working side temporal (P < 0.05) and working side masseter muscle (P < 0.05).
      Muscle activity at various mandibular positions depends greatly on the presence
      of the prosthetic appliance, as edentulous subjects had to use higher muscle
      activity levels (percentages of maximal EMG value) than age matched dentate
      subjects in order to perform same mandibular movement. Different elevator muscles
      were preferentially activated in the edentulous subjects when compared with
      dentate group in lateral excursive positions of the mandible. The pattern of
      relative muscle activity was not changed because of ageing.

PMID- 16457669
TI  - Influence of lip support on the soft-tissue profile of complete denture wearers.
AB  - Complete dentures change the soft-tissue profile, although the exact relationship
      remains unclear. This study examined the relationship between the presence and
      degree of lip support provided by dentures and the lateral views of the facial
      appearance of edentulous patients. The subjects were five edentulous patients
      (three men and two women). Their facial appearances with experimental record
      blocks, with and without their complete dentures, were measured using a three
      dimensional laser measuring system. The experimental record block for each
      subject had different conditions in the anteroposterior direction anteriorly but
      the same vertical dimensions posteriorly. The lateral digital facial images were
      displayed on a computer monitor, and the linear and angular measurements were
      analysed using image analysis software. The nasolabial angle was smaller and the
      labial points projected more with excessive lip support versus with deficient
      support. Moreover, the counter of the nose was affected by the labial flange of
      the record base, particularly in the facial appearance of one subject with highly
      atrophic residual ridges. The lip support affected the lower facial soft-tissue
      profile, including the lower part of the nose; the nasolabial angle and
      positional relationship between the lips and Ricketts's esthetic plane (E plane)
      are useful indexes for examining lip support.

PMID- 16457670
TI  - Effect of adhesive systems associated with resin-modified glass ionomer cements.
AB  - The bonding of resin-modified glass ionomer cements to dentin remains a challenge
      in clinical routine. In an attempt to improve this property, different materials
      and techniques have been proposed. This study investigated the shear bond
      strength of resin-modified glass ionomer cements (Vitremer, 3M/ESPE and Fuji II
      LC Improved, GC) to human dentin using two one-bottle adhesive systems (Prime &
      Bond 2.1, Dentsply and Single Bond, 3M/ESPE). The restored specimens were stored
      in deionized water for 24 h at 37 +/- 1 degrees C, and then the bonded surfaces
      were tested in shear strength using a Universal testing machine at a crosshead
      speed of 0.5 mm min(-1). Bond strength means were recorded and failure modes were
      assessed with a stereomicroscope at 40x magnification. Data were submitted to two
      way anova and multiple comparisons were performed using a Tukey statistical test
      (P < 0.05). Fuji II LC Improved yielded higher bond strength (P < 0.05) than
      Vitremer in all experimental conditions. No statistically significant differences
      (P > 0.05) were observed among the proposed dentin surface treatments, although a
      slight decrease in bond strength was observed when phosphoric acid was used
      alone. Bond strengths of the resin-modified glass ionomer cements to dentin
      seemed to be more material-dependent than surface treatment-dependent. It may be
      concluded that the one-bottle adhesive systems tested in this study did not
      improve the bond strength of the resin-modified glass ionomer cements to dentin.

PMID- 16457671
TI  - Surface roughness of five different dental ceramic core materials after grinding
      and polishing.
AB  - In clinical practice, core materials can be exposed after adjustments are made to
      previously-luted all-ceramic restorations. The purpose of this study was to
      evaluate the surface roughness of five different dental ceramic core materials
      after grinding and polishing. Five different ceramic core materials, Vita In
      Ceram Alumina, Vita In-Ceram Zirconia, IPS Empress 2, Procera AllCeram, and
      Denzir were evaluated. Vita Mark II was used as a reference material. The surface
      roughness, Ra value (mum), was registered using a profilometer. The measurements
      were made before and after grinding with diamond rotary cutting instruments and
      after polishing with the Sof-Lex system. The surface of representative specimens
      was evaluated qualitatively using scanning electron microscopy (SEM). Results
      were statistically analysed using analysis of variance (anova) supplemented with
      Scheffe's and Bonferroni multiple-comparison tests. Before grinding, Procera
      AllCeram and Denzir had the smoothest surfaces, while IPS Empress 2 had the
      coarsest. After grinding, all materials except IPS Empress 2 became coarser.
      Polishing with Sof-Lex provided no significant (P > 0.05) differences between
      Denzir, Vita Mark II and IPS Empress 2 or between Procera AllCeram and In-Ceram
      Zirconia. There were no significant differences (P > 0.05) either between the
      ground and the polished Procera AllCeram or In-Ceram Alumina specimens. Polishing
      of Denzir, IPS Empress 2 and In-Ceram Zirconia made the surfaces smoother
      compared with the state after grinding, whereas the polishing effect on Procera
      AllCeram and In-Ceram Alumina was ineffective. The findings of the SEM evaluation
      were consistent with the profilometer readings.

PMID- 16457672
TI  - Bending resistance of unit cast posts-and-cores compared with noble posts
      following molten cast core attachment.
AB  - The aim of this in vitro study was to evaluate the bending resistance of unit
      cast posts-and-cores (UPC) and prefabricated high noble posts with cast-on cores.
      Tapered posts (ER post-restoring system) of three sizes in diameter (ISO 50, 90,
      110) were investigated: UPC were cast of three different alloys (Au-Pt-Pd, Au-Ag
      Pt, Co-Cr-Mo). Also, prefabricated tapered noble posts (Heraplat and Pt-Ir) were
      cast over with metal cores of the different alloys. Prefabricated titanium posts
      of each size were precision fit into the central core channels of the Co-Cr-Mo
      cores to serve as control specimens. The 0.2% yield strengths (R(0.2)) of all
      specimens were tested on a universal testing machine. One-way and three-way anova
      and Bonferroni-Dunn's multiple comparison tests were performed for the
      statistical analysis. The mean bending resistance R(0.2) of the unit cast posts
      and-cores was 45 +/- 4-46 +/- 5 N for ISO 50 (control group: 54 +/- 3 N), 91 +/-
      9-93 +/- 7 N for ISO 90 (control group: 117 +/- 11 N) and 115 +/- 13-130 +/- 12 N
      for ISO 110 (control group: 141 +/- 12 N). Except for the Au-Pt-Pd UPC of ISO
      110, the yield strengths of the control groups were significantly superior to all
      unit cast alloy combinations (P < 0.05). Significantly lower bending resistance
      was found for Co-Cr-Mo cores cast over Heraplat and Pt-Ir posts compared with the
      corresponding Heraplat/Au-Ag-Pt, Heraplat/Au-Pt-Pd and Pt-Ir/Au-Ag-Pt posts-and
      cores.

PMID- 16457673
TI  - Comparison of curved canals preparations using profile, GT and Hero 642 rotary
      files.
AB  - This study compared preparations of curved canals, using Profile, GT file and
      Hero 642 rotary files. A total of 30 mesiobuccal canals of extracted first and
      second mandibular molars were used in this study. The teeth were embedded in
      resin and a pre-operative radiograph was taken. The specimens were then randomly
      divided into three instrument groups. Pre- and post-instrumentation radiographic
      images were scanned and superimposed using the VISI CAD/CAM program. At nine
      horizontal sections at 1 mm increments from the apex, it calculated pre- and post
      instrumentation cross sectional areas (mm(2)) and enlargements to the inner
      aspect and outer aspects (mm). A Kruskal-Wallis test found no statistical
      difference among the groups in terms of total areas removed by each instrument (P
      > 0.05). It also found no significant difference in any group between the total
      of the inner and outer enlargements (P > 0.05). However the GT file removed
      significantly more material from the outer side of the canal than the inside at
      sections 3-5, and the Hero removed significantly more material from the outer
      side at sections 7-9 (P < 0.05). All instruments produced preparations that
      maintained original canal curvatures.

PMID- 16457674
TI  - Prevalence of root caries in a selected population of older adults in Japan.
AB  - In this study, the prevalence of root caries in a sample of Japanese elders was
      investigated along with various aetiological factors. Two hundred and eighty
      seven independently living elderly people over the age of 60 years were examined
      for the prevalence of active, inactive, and filled root lesions as well as the
      number of teeth. General health, oral status and brushing habits were surveyed,
      and salivary flow was determined in terms of flow rate and subjective feeling of
      dry mouth during eating. About 39% of the subjects had one or more decayed roots
      and 53.3% had at least one decayed or filled lesion. Root caries was seen most
      frequently on canine teeth followed by the first premolar. The number of decayed
      or filled lesions increased with increasing number of residual teeth (Kruskal
      Wallis test, P = 0.033), however, there was no association between the proportion
      of teeth with root decay and the number of teeth. For subjects with 20 or more
      teeth, the number of decayed roots is likely to be lower in subjects who reported
      brushing frequently (P = 0.058), and higher in subjects with low salivary flow (P
      = 0.059) or subjective feeling of dry mouth (P = 0.052) (Chi-squared). The
      presence of decayed lesions is likely to be related to dry mouth (P = 0.057, odds
      ratio 3.13) and brushing frequency (P = 0.088, odds ratio 1.76) (Multiple
      logistic regression analysis). The results indicate a high frequency of root
      surface caries in this Japanese community-dwelling older population. Oral hygiene
      status and low salivary flow or perceived dry mouth were potential risk factors
      for disease.

PMID- 16457675
TI  - 3-Year clinical evaluation of posterior packable composite resin restorations.
AB  - This study evaluated the clinical performance of four packable resin composite
      restorative materials in posterior teeth (Class I and II) compared with one
      hybrid composite after 3 years. Eighty-four restorations were placed in 16
      patients. The tested materials were: (i) Solitaire + Solid Bond; (ii) ALERT +
      Bond-1; (iii) Surefil + Prime & Bond NT; (iv) Filtek P60 + Single Bond and (v)
      TPH Spectrum + Prime & Bond 2.1. All restorations were made using rubber dam
      isolation, and the cavity design was restricted to the elimination of carious
      tissue. Deeper cavities were covered with calcium hydroxide and/or glass-ionomer
      cement. Each adhesive system and composite resin was placed according to the
      manufacturer's instructions. One week later, the restorations were
      finished/polished and evaluated according USPHS modified criteria. Fourteen
      patients attended the 3-year recall and 75 restorations were evaluated at that
      time based on the same evaluation criteria. Friedman repeated measures analysis
      of variance by rank and Wilcoxon sign-ranked test for pair-wise comparison was
      used for data analysis (alpha = 0.05). The analysis was performed only for the
      baseline and for the 3-year period. Solitaire showed some fractures at marginal
      ridges in 25% of the cases. Solitaire and ALERT showed some concerns related to
      colour match (43 and 77%, respectively) and surface texture (86 and 77%,
      respectively). TPH Spectrum showed a great percentage of colour mismatch after 3
      years, around 50%. Surefil and Filtek P60 showed an excellent clinical
      performance after 3 years, similar to the hybrid resin tested, TPH Spectrum.
      Solitaire did not fulfil the ADA acceptance criteria for restorative materials
      and, therefore, is not recommended for use in posterior restorations.

PMID- 16457676
TI  - Dental implants in patients with bruxing habits.
AB  - Bruxism (teeth grinding and clenching) is generally considered a contraindication
      for dental implants, although the evidence for this is usually based on clinical
      experience only. So far, studies to the possible cause-and-effect relationship
      between bruxism and implant failure do not yield consistent and specific
      outcomes. This is partly because of the large variation in the literature in
      terms of both the technical aspects and the biological aspects of the study
      material. Although there is still no proof for the suggestion that bruxism causes
      an overload of dental implants and of their suprastructures, a careful approach
      is recommended. There are a few practical guidelines as to minimize the chance of
      implant failure. Besides the recommendation to reduce or eliminate bruxism
      itself, these guidelines concern the number and dimensions of the implants, the
      design of the occlusion and articulation patterns, and the protection of the
      final result with a hard occlusal stabilization splint (night guard).

PMID- 16457677
TI  - The changing face of professional school health-related journals.

PMID- 16457678
TI  - School absenteeism and school refusal behavior: a review and suggestions for
      school-based health professionals.
AB  - School absenteeism and school refusal behavior are particularly difficult
      problems that school health professionals often face. Unfortunately, few
      recommendations are available to such professionals about how to address this
      population. In this article, we (1) outline the major characteristics of school
      absenteeism and school refusal behavior, (2) review school-based health programs
      that have been designed in part to reduce absenteeism, and (3) provide
      suggestions for school health professionals regarding individual youths with
      school refusal behavior.

PMID- 16457679
TI  - Sports medicine and school nurses: a growing need for further education and
      appropriate resources.
AB  - Sports medicine, as a discipline, can be traced back to primitive man. The use of
      exercise as a prerequisite for conditioning and proper treatment of injuries was
      first documented in early Greek civilization with the establishment of the
      Olympics. Today, sports by their very nature invite injury. In 2000, 2.5 million
      students participated in varsity sports with 750,000 injuries recorded. These
      numbers do not account for sports activities outside school or leisure
      activities. Another area of potential injury is physical education class. These
      classes are large with limited supervision and encompass students of varying age
      and abilities. Nurses do not have an extensive knowledge of injury prevention or
      assessment in their basic nursing education. School nurses, as a subspecialty
      within nursing, are expected to keep up with the requirements of the adolescent
      and pediatric populations as well basic nursing skills. Due to work schedules and
      limited resources for continuing education, school nurses are not afforded much
      time or benefits to attend classes that would teach them skills needed to assess
      athletic-type injuries. School nurses need printed resources specific to their
      setting to help fill this void. Recognizing this need, Sports Medicine Techniques
      for the School-Based Nurse is a manual in process that will help fill this void.
      Being developed specifically for school nurses, the manual will provide
      information on prevention, evaluation, and management of athletic-type injuries
      commonly seen in the school nurse's office.

PMID- 16457680
TI  - Ethnic and socioeconomic comparisons of fitness, activity levels, and barriers to
      exercise in high school females.
AB  - The purpose of this study was to determine if high school females differed in
      individual measures of health-related physical fitness, barriers to exercise, or
      activity level based on ethnicity or socioeconomic status. A cross-sectional
      sample consisting of African American (28%), Hispanic (23%), and white (49%)
      female high school students, 46% from low socioeconomic groups and 54% from
      moderate or high socioeconomic groups (n = 1314, age = 16.2 +/- 0.9) participated
      in this study. A 15-question survey instrument assessed barriers to exercise and
      activity level. The FITNESSGRAM fitness test assessed aerobic capacity and body
      mass index (BMI), and skinfold calipers were used to assess percent body fat.
      Significant differences between African Americans, Hispanics, and whites were
      found on the following dependent variables: BMI, percent fat, mile run, perceived
      barriers to exercise, and activity level. Significant differences between
      socioeconomic groups were found on the following dependent variables: percent
      fat, mile run, activity level, and perceived barriers to exercise. These results
      suggest that students of minority and low socioeconomic groups should be given
      separate and different interventions regarding health-related fitness.

PMID- 16457681
TI  - Asthma status and severity affects missed school days.
AB  - Excessive school absence disrupts learning and is a strong predictor of premature
      school dropout. School-aged children with asthma are absent more often compared
      to their healthy peers without asthma; yet, the causes are inadequately
      documented. We sought to determine the difference in mean absence days between
      children with and without asthma, the relationship between asthma severity and
      missed days from school, and if incident absences were due to asthma in a
      predominantly African American urban school district in the Midwestern United
      States. A cross-sectional analysis was conducted of 9014 students (grades K-12)
      followed for absenteeism over the 2002-2003 academic year. A subset of 543
      students with asthma was assessed for asthma severity and cause of absence. Those
      with asthma (9.7% of students) were absent (mean = 9.2 days) approximately 1.5
      more days compared to those without asthma (mean = 7.9 days) (p = .006). In the
      analysis comparing asthma severity and absenteeism, after adjusting for
      demographic variables and enrollment time, mean days absent increased with
      increasing asthma severity level: mild intermittent (mean = 8.5 days), mild
      persistent (mean = 11.3 days), moderate persistent (mean = 10.3 days), and severe
      persistent (mean = 11.6 days) (p = .001). Out of 1537 tracked absences that
      resulted from illness, 478 (31%) were due specifically to asthma-related
      symptoms. Children with asthma are absent from school more often compared to
      their healthy peers and this appears to be driven by the underlying severity of
      symptoms. (J Sch Health. 2006;76(1):18-24).

PMID- 16457682
TI  - Correlates of the intention to remain sexually inactive among underserved
      Hispanic and African American high school students.
AB  - The objective of this study was to apply the Information-Motivation-Behavior
      (IMB) theoretical framework to examine the correlates of the intention to remain
      sexually inactive among Hispanic and African American high school students. This
      study utilized a cross-sectional survey of high school students. The setting was
      the unified school districts in the County of Los Angeles, California. The
      participants comprised a geographically defined convenience sample of 502
      Hispanic and African American high school students. This study found that only
      50% of this sample reported that they plan to remain sexually abstinent until
      they graduate from high school. Another 21% rejected the notion of remaining
      abstinent, and 29% were uncertain about their intention to engage in sexual
      activities before they graduate from high school. Male and African American
      students were less likely than their female and Latino counterparts to report an
      intention to remain sexually inactive. Using multinomial logistic regression and
      controlling for demographic characteristics, this study documented that students
      with (1) a higher level of perceived peer pressure, (2) a lower level of
      behavioral and refusal skills for avoiding sexual activity, (3) a more positive
      attitude toward practicing safe sex, and (4) a lower level of perceived pregnancy
      repercussions were less likely to claim to remain sexually inactive. The data
      from this study support the IMB model, which suggests that intervention programs
      focusing on knowledge alone are inconsequential in altering the intentions of
      adolescents with respect to their decision to engage in sexual activity.
      Intervention programs should focus on encouraging youth to postpone sexual
      activity by reducing peer pressure and building self-efficacy through enhancing
      motivations and culturally appropriate behavioral skills.

PMID- 16457683
TI  - A multidisciplinary health care team's efforts to improve educational attainment
      in children with sickle-cell anemia and cerebral infarcts.
AB  - The primary objective of this study was to improve the educational success of
      children with sickle-cell disease (SCD) and cerebral infarcts. A prospective
      intervention trial was conducted; a multidisciplinary team was created to
      maximize educational resources for children with SCD and cerebral infarcts.
      Students were evaluated systematically before and after the intervention. A
      baseline evaluation was completed assessing the presence of an Individualized
      Education Plan (IEP), grade retention in school, and days absent from school in
      the year preceding the intervention. A postintervention assessment occurred 2
      years later for these same measurements. At baseline, 74% (17 of 23) of the
      students were receiving IEPs. Two years later, 87% (20 of 23) students received
      IEPs (p = .34). Despite the intervention, the rate of children retained in their
      school grade increased from 0.6 per 100 years in school at baseline to 1.7 per
      100 years, 95% CI (-3.86, 1.49). The school absenteeism rate did not
      significantly change after the intervention; the average days absent per student
      rose from 15.5 to 22.5, (p = .05). The multidisciplinary team effort alone was
      insufficient to decrease grade retention and absenteeism rate. Further support,
      from either the parents or school administration, is needed to increase education
      attainment of students with cerebral infarcts.

PMID- 16457684
TI  - Bridging the gap between research and school health programs.

PMID- 16457685
TI  - The progestational and androgenic properties of medroxyprogesterone acetate: gene
      regulatory overlap with dihydrotestosterone in breast cancer cells.
AB  - INTRODUCTION: Medroxyprogesterone acetate (MPA), the major progestin used for
      oral contraception and hormone replacement therapy, has been implicated in
      increased breast cancer risk. Is this risk due to its progestational or
      androgenic properties? To address this, we assessed the transcriptional effects
      of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in
      human breast cancer cells. METHOD: A new progesterone receptor-negative, androgen
      receptor-positive human breast cancer cell line, designated Y-AR, was engineered
      and characterized. Transcription assays using a synthetic promoter/reporter
      construct, as well as endogenous gene expression profiling comparing
      progesterone, MPA and DHT, were performed in cells either lacking or containing
      progesterone receptor and/or androgen receptor. RESULTS: In progesterone receptor
      positive cells, MPA was found to be an effective progestin through both
      progesterone receptor isoforms in transient transcription assays. Interestingly,
      DHT signaled through progesterone receptor type B. Expression profiling of
      endogenous progesterone receptor-regulated genes comparing progesterone and MPA
      suggested that although MPA may be a somewhat more potent progestin than
      progesterone, it is qualitatively similar to progesterone. To address effects of
      MPA through androgen receptor, expression profiling was performed comparing
      progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene
      regulatory overlap between DHT and MPA through androgen receptor and none with
      progesterone. Interestingly, there was no difference between pharmacological MPA
      and physiological MPA, suggesting that high-dose therapeutic MPA may be
      superfluous. CONCLUSION: Our comparison of the gene regulatory profiles of MPA
      and progesterone suggests that, for physiologic hormone replacement therapy, the
      actions of MPA do not mimic those of endogenous progesterone alone. Clinically,
      the complex pharmacology of MPA not only influences its side-effect profile; but
      it is also possible that the increased breast cancer risk and/or the therapeutic
      efficacy of MPA in cancer treatment is in part mediated by androgen receptor.

PMID- 16457686
TI  - Allelic imbalances of chromosomes 8p and 18q and their roles in distant relapse
      of early stage, node-negative breast cancer.
AB  - INTRODUCTION: Identification of breast cancer patients at risk for postoperative
      distant relapse is an important clinical issue. Existing pathological markers can
      predict disease recurrence only to a certain extent, and there is a need for more
      accurate predictors. METHODS: Using 'counting alleles', a novel experimental
      method, we determined allelic status of chromosomes 8p and 18q in a case-control
      study with 65 early stage, node negative, invasive ductal carcinomas (IDCs). The
      association between allelic imbalance (AI) of both chromosomal markers and
      distant relapses was examined. RESULTS: Eighty percent of tumors contained 8pAI
      and sixty-eight percent of tumors contained 18qAI. However, none of the tumor
      samples retained both chromosome 8p and 18q alleles. More importantly, tumors
      with 8pAI but not 18qAI were more likely to have distant relapse compared to
      tumors with 18qAI but not 8pAI. CONCLUSION: Our finding suggests that
      differential allelic loss of chromosomes 8p and 18q may represent subtypes of
      early stage IDC with different tumor progression behaviors.

PMID- 16457689
TI  - Breast cancer histological classification: agreement between the Office for
      National Statistics and the National Health Service Breast Screening Programme.
AB  - INTRODUCTION: Epidemiological studies rely on data supplied by central cancer
      registration sources to be timely, accurate and complete. Validation studies of
      such data at a national level are limited. Data collected for the Million Women
      Study was used to compare the level of agreement between the Office for National
      Statistics (ONS) and the National Health Service Breast Screening Programme
      (NHSBSP) in the recording of incident screen-detected breast cancer histology
      between 1996 and 2001. METHODS: 1.3 million women aged 50 to 64 years were
      recruited into the Million Women Study cohort via the NHSBSP. Incident screen
      detected breast cancer histologies were notified separately by the ONS and
      NHSBSP. ICD-10 and ICD-02 ONS codes and NHSBSP histology data were similarly
      coded to allow for comparison in terms of cancer invasiveness and morphology. The
      statistical outcome measures are percentage agreement and the kappa statistic.
      RESULTS: A total of 5,886 incident screen-detected breast cancers were available
      for analysis. Of the 5,886 screen-detected cancers reported by the ONS and
      NHSBSP, 5,684 (96.6%, kappa = 0.9) agreed in terms of the degree of invasiveness.
      Of the 5,458 cancers that had been assigned a specific morphology code, there was
      exact agreement between the ONS and the NHSBSP in 4,922 cases (90.2%, kappa =
      0.8). CONCLUSION: There is an excellent level of agreement between the ONS and
      NHSBSP in the recording of the histology of screen-detected breast cancer. From
      these results it is not possible to comment on which source of data is the more
      or less accurate, although the differences are very small.

PMID- 16457688
TI  - Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and
      enhances the effects of insulin-like growth factor-1 on breast epithelial cells.
AB  - INTRODUCTION: CCN6/WISP3 belongs to the CCN (Cyr61, CTGF, Nov) family of genes
      that contains a conserved insulin-like growth factor (IGF) binding protein motif.
      CCN6 is a secreted protein lost in 80% of the aggressive inflammatory breast
      cancers, and can decrease mammary tumor growth in vitro and in vivo. We
      hypothesized that inhibition of CCN6 might result in the loss of a growth
      regulatory function that protects mammary epithelial cells from the tumorigenic
      effects of growth factors, particularly IGF-1. METHOD: We treated human mammary
      epithelial (HME) cells with a CCN6 hairpin short interfering RNA. RESULTS: CCN6
      deficient cells showed increased motility and invasiveness, and developed
      features of epithelial-mesenchymal transition (EMT). Inhibition of CCN6
      expression promoted anchorage-independent growth of HME cells and rendered them
      more responsive to the growth effects of IGF-1, which was coupled with the
      increased phosphorylation of IGF-1 receptor and insulin receptor substrate-1 (IRS
      1). CONCLUSION: Specific stable inhibition of CCN6 expression in HME cells
      induces EMT, promotes anchorage-independent growth, motility and invasiveness,
      and sensitizes mammary epithelial cells to the growth effects of IGF-1.

PMID- 16457687
TI  - HER-2 overexpression differentially alters transforming growth factor-beta
      responses in luminal versus mesenchymal human breast cancer cells.
AB  - INTRODUCTION: Amplification of the HER-2 receptor tyrosine kinase has been
      implicated in the pathogenesis and aggressive behavior of approximately 25% of
      invasive human breast cancers. Clinical and experimental evidence suggest that
      aberrant HER-2 signaling contributes to tumor initiation and disease progression.
      Transforming growth factor beta (TGF-beta) is the dominant factor opposing growth
      stimulatory factors and early oncogene activation in many tissues, including the
      mammary gland. Thus, to better understand the mechanisms by which HER-2
      overexpression promotes the early stages of breast cancer, we directly assayed
      the cellular and molecular effects of TGF-beta1 on breast cancer cells in the
      presence or absence of overexpressed HER-2. METHODS: Cell proliferation assays
      were used to determine the effect of TGF-beta on the growth of breast cancer
      cells with normal or high level expression of HER-2. Affymetrix microarrays
      combined with Northern and western blot analysis were used to monitor the
      transcriptional responses to exogenous TGF-beta1 in luminal and mesenchymal-like
      breast cancer cells. The activity of the core TGF-beta signaling pathway was
      assessed using TGF-beta1 binding assays, phospho-specific Smad antibodies,
      immunofluorescent staining of Smad and Smad DNA binding assays. RESULTS: We
      demonstrate that cells engineered to over-express HER-2 are resistant to the anti
      proliferative effect of TGF-beta1. HER-2 overexpression profoundly diminishes the
      transcriptional responses induced by TGF-beta in the luminal MCF-7 breast cancer
      cell line and prevents target gene induction by a novel mechanism that does not
      involve the abrogation of Smad nuclear accumulation, DNA binding or changes in c
      myc repression. Conversely, HER-2 overexpression in the context of the
      mesenchymal MDA-MB-231 breast cell line potentiated the TGF-beta induced pro
      invasive and pro-metastatic gene signature. CONCLUSION: HER-2 overexpression
      promotes the growth and malignancy of mammary epithelial cells, in part, by
      conferring resistance to the growth inhibitory effects of TGF-beta. In contrast,
      HER-2 and TGF-beta signaling pathways can cooperate to promote especially
      aggressive disease behavior in the context of a highly invasive breast tumor
      model.

PMID- 16457691
TI  - Antisense oligonucleotides targeting the progesterone receptor inhibit hormone
      independent breast cancer growth in mice.
AB  - INTRODUCTION: Previous data from our laboratory suggested that progesterone
      receptors (PRs) are involved in progestin-independent growth of mammary
      carcinomas. To investigate this possibility further, we studied the effects of PR
      antisense oligodeoxynucleotides (asPR) on in vivo tumor growth. METHOD: BALB/c
      mice with subcutaneous 25 mm2 mammary carcinomas expressing estrogen receptor
      alpha and PR were either injected intraperitoneally with 1 mg asPR every 24 or 12
      hours for 5-10 days, or subcutaneously with RU 486 (6.5 mg/kg body weight) every
      24 hours. Control mice received vehicle or scPR. RESULTS: Significant inhibition
      of tumor growth as well as a significant decrease in bromodeoxyuridine uptake was
      observed in asPR-treated mice, which correlated with histological signs of
      regression and increased apoptosis. Mice treated with RU 486 experienced almost
      complete tumor regression. No differences were detected between vehicle-treated
      and scPR-treated mice. Anti-progestin-treated and asPR-treated mice were in a
      continuous estrous/meta-estrous state. Decreased phosphorylated extracellular
      signal-regulated kinase (ERK)1 and ERK2 levels and estrogen receptor-alpha
      expression were observed as late events in RU 486-treated and asPR-treated mice
      with regressing tumors. CONCLUSION: We demonstrate, for the first time,
      inhibition of tumor growth in vivo using asPR. Our results provide further
      evidence for a critical and hierarchical role of the PR pathway in mammary
      carcinomas.

PMID- 16457690
TI  - Effects of combined treatment with rapamycin and cotylenin A, a novel
      differentiation-inducing agent, on human breast carcinoma MCF-7 cells and
      xenografts.
AB  - INTRODUCTION: Rapamycin, an inhibitor of the serine/threonine kinase target of
      rapamycin, induces G1 arrest and/or apoptosis. Although rapamycin and its
      analogues are attractive candidates for cancer therapy, their sensitivities with
      respect to growth inhibition differ markedly among various cancer cells. Using
      human breast carcinoma cell line MCF-7 as an experimental model system, we
      examined the growth-inhibitory effects of combinations of various agents and
      rapamycin to find the agent that most potently enhances the growth-inhibitory
      effect of rapamycin. METHOD: We evaluated the growth-inhibitory effect of
      rapamycin plus various agents, including cotylenin A (a novel inducer of
      differentiation of myeloid leukaemia cells) to MCF-7 cells, using either MTT
      assay or trypan blue dye exclusion test. The cell cycle was analyzed using
      propidium iodide-stained nuclei. Expressions of several genes in MCF-7 cells with
      rapamycin plus cotylenin A were studied using cDNA microarray analysis and RT
      PCR. The in vitro results of MCF-7 cells treated with rapamycin plus cotylenin A
      were further confirmed in vivo in a mouse xenograft model. RESULTS: We found that
      the sensitivity of rapamycin to MCF-7 cells was markedly affected by cotylenin A.
      This treatment induced growth arrest of the cells at the G1 phase, rather than
      apoptosis, and induced senescence-associated beta-galactosidase activity. We
      examined the gene expression profiles associated with exposure to rapamycin and
      cotylenin A using cDNA microarrays. We found that expressions of cyclin G2,
      transforming growth factor-beta-induced 68 kDa protein, BCL2-interacting killer,
      and growth factor receptor-bound 7 were markedly induced in MCF-7 cells treated
      with rapamycin plus cotylenin A. Furthermore, combined treatment with rapamycin
      and cotylenin A significantly inhibited the growth of MCF-7 cells as xenografts,
      without apparent adverse effects. CONCLUSION: Rapamycin and cotylenin A
      cooperatively induced growth arrest in breast carcinoma MCF-7 cells in vitro, and
      treatment with rapamycin and cotylenin A combined more strongly inhibited the
      growth of MCF-7 cells as xenografts in vivo than treatment with rapamycin or
      cotylenin A alone, suggesting that this combination may have therapeutic value in
      treating breast cancer. We also identified several genes that were markedly
      modulated in MCF-7 cells treated with rapamycin plus cotylenin A.

PMID- 16457692
TI  - Nipple aspiration and ductal lavage in women with a germline BRCA1 or BRCA2
      mutation.
AB  - INTRODUCTION: The aim of this study was to collect serial samples of nipple
      aspirate (NA) and ductal lavage (DL) fluid from women with germline BRCA1/2
      mutations in order to create a biorepository for use in identifying biomarkers of
      breast cancer risk. METHODS: Between March 2003 and February 2005, 52 women with
      germline BRCA1 or BRCA2 mutations (median age 43 years, range 27 to 65 years)
      were scheduled for six-monthly NA, DL and venesection. DL was attempted for all
      NA fluid-yielding (FY) and any non-FY ducts that could be located at each visit.
      RESULTS: Twenty-seven (52%) women were postmenopausal, predominantly (19/27) from
      risk reducing bilateral salpingo-oophorectomy (BSO). FY ducts were identified in
      60% of all women, 76% of premenopausal women versus 44% of postmenopausal (P =
      0.026). Eighty-five percent of women had successful DL. Success was most likely
      in women with FY ducts (FY 94% versus non-FY 71% (P = 0.049). DL samples were
      more likely to be cellular if collected from FY ducts (FY 68% versus non-FY 43%;
      P = 0.037). Total cell counts were associated with FY status (FY median cell
      count 30,996, range 0 to >1,000,000 versus non-FY median cell count 0, range 0 to
      173,577; P = 0.002). Four women (8%) had ducts with severe atypia with or without
      additional ducts with mild epithelial atypia; seven others had ducts with mild
      atypia alone (11/52 (21%) in total). Median total cell count was greater from
      ducts with atypia (105,870, range 1920 to >1,000,000) than those with no atypia
      (174, 0 to >1,000,000; P <or= 0.001). CONCLUSION: It is feasible to collect
      serial NA and DL samples from women at high genetic risk of breast cancer, and we
      are creating a unique, prospective collection of ductal samples that have the
      potential to be used for discovery of biomarkers of breast cancer risk and
      evaluate the ongoing effects of risk reducing BSO. DL cellular atypia was not
      predictive of a current breast cancer and longer follow up is needed to determine
      whether atypia is an additional marker of future breast cancer risk in this
      population already at high genetic risk of breast cancer.

PMID- 16457693
TI  - Dehydroepiandrosterone inhibits the progression phase of mammary carcinogenesis
      by inducing cellular senescence via a p16-dependent but p53-independent
      mechanism.
AB  - INTRODUCTION: Dehydroepiandrosterone (DHEA), an adrenal 17-ketosteroid, is a
      precursor of testosterone and 17beta-estradiol. Studies have shown that DHEA
      inhibits carcinogenesis in mammary gland and prostate as well as other organs, a
      process that is not hormone dependent. Little is known about the molecular
      mechanisms of DHEA-mediated inhibition of the neoplastic process. Here we examine
      whether DHEA and its analog DHEA 8354 can suppress the progression of
      hyperplastic and premalignant (carcinoma in situ) lesions in mammary gland toward
      malignant tumors and the cellular mechanisms involved. METHODS: Rats were treated
      with N-nitroso-N-methylurea and allowed to develop mammary hyperplastic and
      premalignant lesions with a maximum frequency 6 weeks after carcinogen
      administration. The animals were then given DHEA or DHEA 8354 in the diet at 125
      or 1,000 mg/kg diet for 6 weeks. The effect of these agents on induction of
      apoptosis, senescence, cell proliferation, tumor burden and various effectors of
      cellular signaling were determined. RESULTS: Both agents induced a dose-dependent
      decrease in tumor multiplicity and in tumor burden. In addition they induced a
      senescent phenotype in tumor cells, inhibited cell proliferation and increased
      the number of apoptotic cells. The DHEA-induced cellular effects were associated
      with increased expression of p16 and p21, but not p53 expression, implicating a
      p53-independent mechanism in their action. CONCLUSION: We provide evidence that
      DHEA and DHEA 8354 can suppress mammary carcinogenesis by altering various
      cellular functions, inducing cellular senescence, in tumor cells with the
      potential involvement of p16 and p21 in mediating these effects.

PMID- 16457694
TI  - Preclinical evaluation of transcriptional targeting strategies for carcinoma of
      the breast in a tissue slice model system.
AB  - INTRODUCTION: In view of the limited success of available treatment modalities
      for metastatic breast cancer, alternative and complementary strategies need to be
      developed. Adenoviral vector mediated strategies for breast cancer gene therapy
      and virotherapy are a promising novel therapeutic platform for the treatment of
      breast cancer. However, the promiscuous tropism of adenoviruses (Ads) is a major
      concern. Employing tissue specific promoters (TSPs) to restrict transgene
      expression or viral replication is an effective way to increase specificity
      towards tumor tissues and to reduce adverse effects in non-target tissues such as
      the liver. In this regard, candidate breast cancer TSPs include promoters of the
      genes for the epithelial glycoprotein 2 (EGP-2), cyclooxygenase-2 (Cox-2), alpha
      chemokine SDF-1 receptor (stromal-cell-derived factor, CXCR4), secretory
      leukoprotease inhibitor (SLPI) and survivin. METHODS: We employed E1-deleted Ads
      that express the reporter gene luciferase under the control of the promoters of
      interest. We evaluated this class of vectors in various established breast cancer
      cell lines, primary breast cancer cells and finally in the most stringent
      preclinical available substrate system, constituted by precision cut tissue
      slices of human breast cancer and liver. RESULTS: Overall, the CXCR4 promoter
      exhibited the highest luciferase activity in breast cancer cell lines, primary
      breast cancer cells and breast cancer tissue slices. Importantly, the CXCR4
      promoter displayed a very low activity in human primary fibroblasts and human
      liver tissue slices. Interestingly, gene expression profiles correlated with the
      promoter activities both in breast cancer cell lines and primary breast cancer
      cells. CONCLUSION: These data suggest that the CXCR4 promoter has an ideal
      'breast cancer-on/liver-off' profile, and could, therefore, be a powerful tool in
      Ad vector based gene therapy or virotherapy of the carcinoma of the breast.

PMID- 16457695
TI  - Tamoxifen may prevent both ER+ and ER- breast cancers and select for ER-
      carcinogenesis: an alternative hypothesis.
AB  - INTRODUCTION: Breast Cancer Prevention Trial (BCPT) and Multiple Outcomes of
      Raloxifene (MORE) data have been interpreted to indicate that tamoxifen reduces
      the risk of ER+ but not ER- breast carcinogenesis. We explored whether these data
      also support an alternative hypothesis, that tamoxifen influences the natural
      history of both ER+ and ER- cancers, that it may be equally effective in
      abrogating or delaying ER- and ER+ carcinogenesis, and place selection pressure,
      in some cases, for the outgrowth of ER- cancers. METHODS: BCPT and MORE data were
      used to investigate whether: first, tamoxifen could reduce equally the emergence
      of ER- and ER+ tumors; and second, tamoxifen could select a fraction of emerging
      ER+ cancers and promote their transformation to ER- cancers. Assuming that some
      proportion, Z, of ER+ tumors becomes ER- after tamoxifen exposure and that the
      risk reduction for both ER- and ER+ tumors is equal, we solved for both the
      transformation rate and the risk reduction rate. RESULTS: If tamoxifen equally
      reduces the incidence of ER+ and ER- tumors by 60%, the BCPT results are achieved
      with a transformation of approximately Z = 20% of ER+ to ER- tumors. Validation
      with MORE data using an equal risk reduction of 60% associated with tamoxifen
      produces an almost identical transformation rate Z of 23%. CONCLUSION: Data
      support an alternative hypothesis that tamoxifen may promote ER- carcinogenesis
      from a precursor lesion that would otherwise have developed as ER+ without
      tamoxifen selection.

PMID- 16457697
TI  - A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms
      and breast cancer risk.
AB  - INTRODUCTION: The gene XRCC1 (X-ray repair cross-complementing group 1) encodes a
      protein involved in DNA base excision repair. Two non-synonymous polymorphisms in
      XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in
      some studies in vitro. However, results of previous association studies of these
      two XRCC1 variants and breast cancer have been inconsistent. We examined the
      association between polymorphisms in XRCC1 and breast cancer in the American
      Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a large
      prospective study of cancer incidence in the USA. METHODS: Among the 21,965 women
      who were cancer-free in 1992 and gave blood between 1998 and 2001, 502
      postmenopausal breast cancer cases were diagnosed between 1992 and 2001; 502
      controls were matched to cases on age, race/ethnicity, and date of blood
      collection. Genotyping on DNA extracted from buffy coat was performed with
      Taqman. Conditional logistic regression was used to examine the association
      between each polymorphism and breast cancer risk controlling for breast cancer
      risk factors. We also examined whether factors associated with DNA damage, such
      as smoking and antioxidant intake, modified the association between XRCC1
      polymorphisms and breast cancer. RESULTS: We observed a significant inverse
      association between Trp194 carriers (Trp/Trp and Trp/Arg) compared with Trp194
      non-carriers in relation to breast cancer (Arg/Arg) (odds ratio (OR) 0.62, 95%
      confidence interval (CI) 0.40 to 0.95). The inverse association between breast
      cancer and Trp194 carriers compared with non-carriers was slightly stronger among
      smokers (OR 0.47, 95% CI 0.24 to 0.94) than never smokers (OR 0.78, 95% CI 0.43
      to 1.40). An increased risk associated with the Arg399Gln polymorphism (Gln/Gln
      versus Arg/Arg) was observed only among women who reported ever smoking
      cigarettes (OR 2.76, 95% CI 1.36 to 5.63), and not in women who were lifelong non
      smokers (OR 0.64, 95% CI 0.33 to 1.26). No other factor examined modified the
      association between XRCC1 polymorphisms and breast cancer risk. CONCLUSION: Our
      results support the hypothesis that genetic variation in XRCC1, particularly in
      Arg194Trp, may influence postmenopausal breast cancer risk. In our study, genetic
      variation in XRCC1 Arg399Gln was associated with breast cancer risk only among
      women with a history of smoking cigarettes.

PMID- 16457696
TI  - Farnesyl-transferase inhibitor R115,777 enhances tamoxifen inhibition of MCF-7
      cell growth through estrogen receptor dependent and independent pathways.
AB  - INTRODUCTION: We have previously shown that FTI-277, a farnesyl transferase
      inhibitor (FTI), enhances the efficacy of tamoxifen (Tam) in inhibiting the
      proliferation of the estrogen dependent MCF-7 cell line. As the cellular response
      to Tam is the result of an inhibition of both estrogen receptor-dependent and 
      independent pathways, we have used the estrogen receptor selective anti-estrogen
      ICI182,780 and N-pyrrolidine(-phenylmethyl-phenoxy)-ethanamine-HCl (PBPE), a
      selective ligand of anti-estrogen binding site (AEBS), to dissect out the
      mechanism(s) associated with the observed additivity resulting from combination
      treatment with FTI-277 and Tam. Moreover, for these studies, FTI-277 has been
      replaced by R115,777, a FTI currently in phase III clinical trials. METHODS: The
      quantitative sulphorhodamine B (SRB) colorimetric assay was used to determine the
      growth inhibitory effect of agents on MCF-7 cells. Dose response interactions
      between R115,777-Tam, R115,777-ICI182,780 and R115,777-PBPE were evaluated, at
      the IC50 point, using the isobologram method. Apoptotic cell death (DNA
      fragmentation, nucleus condensation and cytokeratin 18 cleavage) and inhibition
      of the mevalonate pathway (western blot) were also determined. RESULTS:
      Combinations of the specific FTI R115,777 with either ICI182,780 or PBPE exhibit
      a synergistic effect on MCF-7 cell growth inhibition, while its combination with
      Tam is additive, as previously reported for FTI-277. Apoptosis is detected after
      treatment with combinations of R115,777 with either Tam or PBPE but not with
      ICI182,780, suggesting that each combination inhibits cell proliferation by
      different mechanisms. Even though the ER pathway has not yet been deciphered, it
      is shown here that the AEBS pathway is able to interfere with the mevalonate
      pathway at the level of protein farnesylation. CONCLUSION: Overall, this work
      reveals that combinations of R115,777 with either selective ER ligands or a
      selective AEBS ligand are able to induce large increases in their anti
      proliferative activities on MCF-7 cells. Moreover, these results suggest that it
      may be of definite interest to evaluate combinations of R115,777 with different
      anti-estrogens in the treatment of ER positive breast tumours. Based on these
      experimental data, such combinations may prove beneficial in different clinical
      scenarios or when used in specific sequences; studying the combination of
      R115,777 with ICI182,780 for early treatment and reserving combinations with
      either Tam or a selective AEBS ligand, such as BMS-217380-01, for more resistant
      disease.

PMID- 16457700
TI  - Aromatase inhibitors as adjuvant therapy for postmenopausal women: a therapeutic
      advance but many unresolved questions.
AB  - Adjuvant hormonal therapy for postmenopausal women with early stage breast cancer
      has become far more complex over the past several years. This commentary reviews
      the current status of the five major trials evaluating the use of the aromatase
      inhibitors in the adjuvant setting. The data currently available suggest that the
      aromatase inhibitors are efficacious either as upfront therapy or after a course
      of tamoxifen. Ongoing trials will compare these approaches and guide the use of
      these agents in the years to come.

PMID- 16457698
TI  - Prognostic relevance of disseminated tumor cells in the bone marrow and
      biological factors of 265 primary breast carcinomas.
AB  - INTRODUCTION: The prognostic significance of disseminated tumor cells in the bone
      marrow (DTC-BM) of breast cancer patients has been demonstrated in many studies.
      Yet, it is not clear which of the primary tumors' biological factors predict
      hematogenous dissemination. We therefore examined 'tissue micro arrays' (TMAs) of
      265 primary breast carcinomas from patients with known bone marrow (BM) status
      for HER2, Topoisomerase IIalpha (Top IIa), Ki 67, and p53. METHODS: BM analysis
      was performed by cytospin preparation and immunocytochemical staining for
      cytokeratin (CK). TMAs were examined by immunohistochemistry (IHC) for HER2, Top
      IIa, Ki 67 and p53, and fluorescence in situ hybridization (FISH) for HER2.
      RESULTS: HER2 (2+/3+) was positive in 35/167 (21%) cases (FISH 24.3%), Top IIa
      (>10%) in 87/187 (46%), Ki 67 in 52/184 (28%) and p53 (>5%) in 61/174 cases
      (34%). Of 265 patients, 68 (25.7%) showed DTC-BM with a median of 2/2 x 106 cells
      (1 to 1,500). None of the examined factors significantly predicted BM positivity.
      Significant correlation was seen between HER2 IHC and Top IIa (p = 0.06), Ki 67
      (p = 0.031), and p53 (p < .001). Top IIa correlated with Ki 67 and p53, and Ki 67
      also with p53 (p = 0.004). After a median follow-up of 60.5 months (7 to 255),
      the presence of DTC-BM showed prognostic relevance for overall survival (p =
      0.03), whereas HER2 (IHC, p = 0.04; FISH, p = 0.03) and Ki 67 (p = 0.04)
      correlated with disease free survival, and HER2 with distant disease free
      survival (IHC, p = 0.06; FISH, p = 0.05). DISCUSSION: The congruence of the
      examined factors' expression rates indicates a causal line of suppressor,
      proliferation, and mitosis markers, and growth factor receptors. Hematogenous
      tumor cell spread seems to be an independent process. The examination of these
      factors on DTC-BM is the aim of ongoing research.

PMID- 16457699
TI  - High resolution genomic analysis of sporadic breast cancer using array-based
      comparative genomic hybridization.
AB  - INTRODUCTION: Genomic aberrations in the form of subchromosomal DNA copy number
      changes are a hallmark of epithelial cancers, including breast cancer. The goal
      of the present study was to analyze such aberrations in breast cancer at high
      resolution. METHODS: We employed high-resolution array comparative genomic
      hybridization with 4,134 bacterial artificial chromosomes that cover the genome
      at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast
      cancer cell lines. RESULTS: Common amplicons included 8q24.3 (amplified in 79% of
      tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3
      (amplified in 66% and 57% of tumors, respectively). Moreover, we found several
      positive correlations between specific amplicons from different chromosomes,
      suggesting the existence of cooperating genetic loci. Queried by gene, the most
      frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently
      lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2
      as measured by comparative genomic hybridization (CGH) correlated closely with
      ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2
      protein levels. The overall frequency of recurrent losses was lower, with no
      region lost in more than 50% of tumors; the most frequently lost tumor suppressor
      gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific
      copy number changes in cell lines closely mimicked those in primary tumors, with
      an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for
      losses. CONCLUSION: High resolution CGH analysis of breast cancer reveals several
      regions where DNA copy number is commonly gained or lost, that non-random
      correlations between specific amplicons exist, and that specific genetic
      alterations are maintained in breast cancer cell lines despite repeat passage in
      tissue culture. These observations suggest that genes within these regions are
      critical to the malignant phenotype and may thus serve as future therapeutic
      targets.

PMID- 16457701
TI  - Overdiagnosis and overtreatment of breast cancer: estimates of overdiagnosis from
      two trials of mammographic screening for breast cancer.
AB  - Randomised controlled trials have shown that the policy of mammographic screening
      confers a substantial and significant reduction in breast cancer mortality. This
      has often been accompanied, however, by an increase in breast cancer incidence,
      particularly during the early years of a screening programme, which has led to
      concerns about overdiagnosis, that is to say, the diagnosis of disease that, if
      left undetected and therefore untreated, would not become symptomatic. We used
      incidence data from two randomised controlled trials of mammographic screening,
      the Swedish Two-county Trial and the Gothenburg Trial, to establish the timing
      and magnitude of any excess incidence of invasive disease and ductal carcinoma in
      situ (DCIS) in the study groups, to ascertain whether the excess incidence of
      DCIS reported early in a screening trial is balanced by a later deficit in
      invasive disease and provide explicit estimates of the rate of 'real' and non
      progressive 'overdiagnosed' tumours from the study groups of the trials. We used
      a multistate model for overdiagnosis and used Markov Chain Monte Carlo methods to
      estimate the parameters. After taking into account the effect of lead time, we
      estimated that less than 5% of cases diagnosed at prevalence screen and less than
      1% of cases diagnosed at incidence screens are being overdiagnosed. Overall, we
      estimate overdiagnosis to be around 1% of all cases diagnosed in screened
      populations. These estimates are, however, subject to considerable uncertainty.
      Our results suggest that overdiagnosis in mammography screening is a minor
      phenomenon, but further studies with very large numbers are required for more
      precise estimation.

PMID- 16457702
TI  - Overdiagnosis and overtreatment of breast cancer: overdiagnosis and overtreatment
      in service screening.
AB  - Screening mammography has been shown to be effective for reducing breast cancer
      mortality. According to screening theory, the first expected consequence of
      mammography screening is the detection of the disease at earlier stages and this
      diagnostic anticipation changes the population incidence curve, with an observed
      increase in incidence rates at earlier ages. It is unreasonable to expect that
      the age-specific incidence will ever return to pre-screening levels or to
      anticipate a significant reduction of incidence at older ages immediately after
      the first screening round. The interpretation of incidence trends, especially in
      the short term, is difficult. Methodology for quantification of overdiagnosis and
      statistical modelling based on service screening data is not well developed and
      few population-based studies are available. The overtreatment issue is discussed
      in terms of appropriateness of effective treatment considering the question of
      chemotherapy in very early stages and the use of breast conserving surgery.

PMID- 16457703
TI  - Overdiagnosis and overtreatment of breast cancer: rates of ductal carcinoma in
      situ: a US perspective.
AB  - The incidence of breast ductal carcinoma in situ (DCIS) in the USA exceeds that
      of other countries. This cannot be explained entirely by the frequency of
      mammographic screening in the USA and may result from differences in the
      interpretation of mammograms and/or the frequency with which biopsies are
      obtained. Although the percentage of DCIS patients treated with mastectomy has
      decreased, the absolute number is unchanged and the use of lumpectomy with whole
      breast radiotherapy has increased in inverse proportion to the decrease in
      mastectomy. Treatment of DCIS with tamoxifen is still limited.

PMID- 16457704
TI  - Imaging in breast cancer - breast cancer imaging revisited.

PMID- 16457705
TI  - Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in
      pre-menopausal women and monitoring neoadjuvant chemotherapy.
AB  - Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are non
      invasive diagnostic techniques that employ near-infrared (NIR) light to
      quantitatively characterize the optical properties of centimeter-thick, multiple
      scattering tissues. Although NIR was first applied to breast diaphanography more
      than 70 years ago, quantitative optical methods employing time- or frequency
      domain 'photon migration' technologies have only recently been used for breast
      imaging. Because their performance is not limited by mammographic density,
      optical methods can provide new insight regarding tissue functional changes
      associated with the appearance, progression, and treatment of breast cancer,
      particularly for younger women and high-risk subjects who may not benefit from
      conventional imaging methods. This paper reviews the principles of diffuse optics
      and describes the development of broadband DOS for quantitatively measuring the
      optical and physiological properties of thick tissues. Clinical results are shown
      highlighting the sensitivity of diffuse optics to malignant breast tumors in 12
      pre-menopausal subjects ranging in age from 30 to 39 years and a patient
      undergoing neoadjuvant chemotherapy for locally advanced breast cancer.
      Significant contrast was observed between normal and tumor regions of tissue for
      deoxy-hemoglobin (p = 0.005), oxy-hemoglobin (p = 0.002), water (p = 0.014), and
      lipids (p = 0.0003). Tissue hemoglobin saturation was not found to be a reliable
      parameter for distinguishing between tumor and normal tissues. Optical data were
      converted into a tissue optical index that decreased 50% within 1 week in
      response to neoadjuvant chemotherapy. These results suggest a potential role for
      diffuse optics as a bedside monitoring tool that could aid the development of new
      strategies for individualized patient care.

PMID- 16457706
TI  - Nestin expression in the cell lines derived from glioblastoma multiforme.
AB  - BACKGROUND: Nestin is a protein belonging to class VI of intermediate filaments
      that is produced in stem/progenitor cells in the mammalian CNS during development
      and is consecutively replaced by other intermediate filament proteins
      (neurofilaments, GFAP). Down-regulated nestin may be re-expressed in the adult
      organism under certain pathological conditions (brain injury, ischemia,
      inflammation, neoplastic transformation). Our work focused on a detailed study of
      the nestin cytoskeleton in cell lines derived from glioblastoma multiforme,
      because re-expression of nestin together with down-regulation of GFAP has been
      previously reported in this type of brain tumor. METHODS: Two cell lines were
      derived from the tumor tissue of patients treated for glioblastoma multiforme.
      Nestin and other cytoskeletal proteins were visualized using imunocytochemical
      methods: indirect immunofluorescence and immunogold-labelling. RESULTS: Using
      epifluorescence and confocal microscopy, we described the morphology of nestin
      positive intermediate filaments in glioblastoma cells of both primary cultures
      and the derived cell lines, as well as the reorganization of nestin during
      mitosis. Our most important result came through transmission electron microscopy
      and provided clear evidence that nestin is present in the cell nucleus.
      CONCLUSION: Detailed information concerning the pattern of the nestin
      cytoskeleton in glioblastoma cell lines and especially the demonstration of
      nestin in the nucleus represent an important background for further studies of
      nestin re-expression in relationship to tumor malignancy and invasive potential.

PMID- 16457707
TI  - Nutritional care of medical inpatients: a health technology assessment.
AB  - BACKGROUND: The inspiration for the present assessment of the nutritional care of
      medical patients is puzzlement about the divide that exists between the
      theoretical knowledge about the importance of the diet for ill persons, and the
      common failure to incorporate nutritional aspects in the treatment and care of
      the patients. The purpose is to clarify existing problems in the nutritional care
      of Danish medical inpatients, to elucidate how the nutritional care for these
      inpatients can be improved, and to analyse the costs of this improvement.
      METHODS: Qualitative and quantitative methods are deployed to outline how
      nutritional care of medical inpatients is performed at three Danish hospitals.
      The practices observed are compared with official recommendations for nutritional
      care of inpatients. Factors extraneous and counterproductive to optimal
      nutritional care are identified from the perspectives of patients and
      professional staff. A review of the literature illustrates the potential for
      optimal nutritional care. A health economic analysis is performed to elucidate
      the savings potential of improved nutritional care. RESULTS: The prospects for
      improvements in nutritional care are ameliorated if hospital management clearly
      identifies nutritional care as a priority area, and enjoys access to management
      tools for quality assurance. The prospects are also improved if a committed
      professional at the ward has the necessary time resources to perform nutritional
      care in practice, and if the care staff can requisition patient meals rich in
      nutrients 24 hours a day. At the kitchen production level prospects benefit from
      a facilitator contact between care and kitchen staff, and if the kitchen staff
      controls the whole food path from the kitchen to the patient. At the patient
      level, prospects are improved if patients receive information about the choice of
      food and drink, and have a better nutrition dialogue with the care staff. Better
      nutritional care of medical patients in Denmark is estimated to hold a cost
      savings potential reaching approximately USD 22 million. CONCLUSION: Every
      hospital and every bed ward has its strengths and weaknesses, but none of the
      participating bed wards fully satisfy nutritional care success criteria. All
      organisational levels have a significant potential for improvements of
      nutritional care of medical inpatients.

PMID- 16457708
TI  - On the attenuation and amplification of molecular noise in genetic regulatory
      networks.
AB  - BACKGROUND: Noise has many important roles in cellular genetic regulatory
      functions at the nanomolar scale. At present, no good theory exists for
      identifying all possible mechanisms of genetic regulatory networks to attenuate
      the molecular noise to achieve regulatory ability or to amplify the molecular
      noise to randomize outcomes to the advantage of diversity. Therefore, the noise
      filtering of genetic regulatory network is an important topic for gene networks
      under intrinsic fluctuation and extrinsic noise. RESULTS: Based on stochastic
      dynamic regulation equation, the intrinsic fluctuation in reaction rates is
      modeled as a state-dependent stochastic process, which will influence the
      stability of gene regulatory network, especially, with low concentrations of
      reacting species. Then the mechanisms of genetic regulatory network to attenuate
      or amplify extrinsic fluctuation are revealed from the nonlinear stochastic
      filtering point of view. Furthermore, a simple measure of attenuation level or
      amplification level of extrinsic noise for genetic regulatory networks is also
      introduced by nonlinear robust filtering method. Based on the global
      linearization scheme, a convenient method is introduced to measure noise
      attenuation or amplification for each gene of the nonlinear stochastic regulatory
      network by solving a set of filtering problems, which correspond to a set of
      linearized stochastic regulatory networks. Finally, by the proposed methods,
      several simulation examples of genetic regulatory networks are given to measure
      their robust stability under intrinsic fluctuations, and to estimate the genes'
      attenuation and amplification levels under extrinsic noises. CONCLUSION: In this
      study, a stochastic nonlinear dynamic model is developed for genetic regulatory
      networks under intrinsic fluctuation and extrinsic noise. By the method we
      proposed, we could determine the robust stability under intrinsic fluctuations
      and identify the genes that are significantly affected by extrinsic noises, which
      we call the weak structure of the network. This method will be potential for
      robust gene circuit design in future, on which a drug design could be based.

PMID- 16457709
TI  - Generation, annotation, and analysis of an extensive Aspergillus niger EST
      collection.
AB  - BACKGROUND: Aspergillus niger, a saprophyte commonly found on decaying
      vegetation, is widely used and studied for industrial purposes. Despite its place
      as one of the most important organisms for commercial applications, the lack of
      available information about its genetic makeup limits research with this
      filamentous fungus. RESULTS: We present here the analysis of 12,820 expressed
      sequence tags (ESTs) generated from A. niger cultured under seven different
      growth conditions. These ESTs identify about 5,108 genes of which 44.5% code for
      proteins sharing similarity (E < or = 1e(-5)) with GenBank entries of known
      function, 38% code for proteins that only share similarity with GenBank entries
      of unknown function and 17.5% encode proteins that do not have a GenBank homolog.
      Using the Gene Ontology hierarchy, we present a first classification of the A.
      niger proteins encoded by these genes and compare its protein repertoire with
      other well-studied fungal species. We have established a searchable web-based
      database that includes the EST and derived contig sequences and their annotation.
      Details about this project and access to the annotated A. niger database are
      available. CONCLUSION: This EST collection and its annotation provide a
      significant resource for fundamental and applied research with A. niger. The gene
      set identified in this manuscript will be highly useful in the annotation of the
      genome sequence of A. niger, the genes described in the manuscript, especially
      those encoding hydrolytic enzymes will provide a valuable source for researchers
      interested in enzyme properties and applications.

PMID- 16457710
TI  - Differing myocardial response to a single session of hemodialysis in end-stage
      renal disease with and without type 2 diabetes mellitus and coronary artery
      disease.
AB  - BACKGROUND: Though hemodialysis (HD) acutely improves cardiac function, the
      impact of background diseases like coronary artery disease (CAD) and Type 2
      diabetes (DM) in the setting of end-stage renal disease (ESRD) is not known.
      Tissue velocity echocardiography (TVE) offers a fast choice to follow changes in
      myocardial function after HD in ESRD with concomitant DM and /or CAD. METHODS: 46
      subjects (17 with ESRD, Group 1; 15 with DM, Group 2; 14 with DM+CAD, Group 3)
      underwent standard and TVE prior to and shortly after HD. Besides standard
      Doppler variables, regional myocardial systolic and diastolic velocities, as well
      as systolic strain rate were post processed. RESULTS: Compared with pre-HD, post
      HD body weight (kg) significantly decreased in all the three groups (51 +/- 9 vs.
      48 +/- 8, 62 +/- 10 vs.59 +/- 10, and 61 +/- 9 vs. 58 +/- 9 respectively; all p <
      0.01). Left ventricular end diastolic dimensions (mm) also decreased post- HD (46
      +/- 5 vs. 42 +/- 7, 53 +/- 7 vs. 50 +/- 7, 51 +/- 7 vs. 47 +/- 8 respectively;
      all p < 0.01). Regional longitudinal peak systolic velocity in septum (cm/s)
      significantly increased post-HD in Group 1(5.7 +/- 1.6 vs. 7.2 +/- 2.3; p <
      0.001) while remained unchanged in the other two groups. Similar trends were
      noted in other left ventricular walls. When the myocardial velocities (cm/s) were
      computed globally, the improvement was seen only in Group 1 (6.3 +/- 1.5 vs. 7.9
      +/- 2.0; p < 0.001). Global early regional diastolic velocity (cm/s) improved in
      Group 1, remained unchanged in Group 2, while significantly decreased in Group 3(
      5.9 +/- 1.3 vs. -4.1 +/- 1.8; p < 0.01). Global systolic strain rate (1/sec)
      increased in the first 2 Groups but remained unchanged (-0.87 +/- 0.4 vs. -0.94
      +/- 0.3; p = ns) in Group 3. CONCLUSION: A single HD session improves LV function
      only in ESRD without coexistent DM and/or CAD. The present data suggest that not
      only dialysis-dependent changes in loading conditions but also co-existent
      background diseases determine the myocardial response to HD.

PMID- 16457711
TI  - Identification of pain indicators for infants at risk for neurological
      impairment: a Delphi consensus study.
AB  - BACKGROUND: A number of infant pain measures have been developed over the past 15
      years incorporating behavioural and physiologic indicators; however, no reliable
      or valid measure exists for infants who are at risk for neurological impairments
      (NI). The objective of this study was to establish consensus about which
      behavioural, physiologic and contextual indicators best characterize pain in
      infants at high, moderate and low levels of risk for NI. METHODS: A 39- item,
      self-administered electronic survey that included infant physiologic, behavioral
      and contextual pain indicators was used in a two round Delphi consensus exercise.
      Fourteen pediatric pain experts were polled individually and anonymously on the
      importance and usefulness of the pain indicators for the 3 differing levels of
      risk for NI. RESULTS: The strength of agreement between expert raters was
      moderate in Round 1 and fair in Round 2. In general, pain indicators with the
      highest concordance for all three groups were brow bulge, facial grimace, eye
      squeeze, and inconsolability. Increased heart rate from baseline in the moderate
      and severe groups demonstrated high concordance. In the severe risk group,
      fluctuations in heart rate and reduced oxygen saturation were also highly rated.
      CONCLUSION: These data constitute the first step in contributing to the
      development and validation of a pain measure for infants at risk for NI. In
      future research, we will integrate these findings with the opinions of (a) health
      care providers about the importance and usefulness of infant pain indicators and
      (b) the pain responses of infants at mild, moderate and high risk for NI.

PMID- 16457713
TI  - Development and validation of an Opioid Attractiveness Scale: a novel measure of
      the attractiveness of opioid products to potential abusers.
AB  - BACKGROUND: The growing trends in opioid abuse, assessment of the abuse liability
      of prescription opioid products, and growing efforts by the pharmaceutical
      industry to develop 'abuse-resistant' formulations highlight a need to understand
      the features that make one product more 'attractive' than another to potential
      abusers. We developed a scale to measure the 'attractiveness' of prescription
      opioids to potential abusers, and used the scale to measure the relative
      attractiveness of 14 opioid analgesic products. METHODS: First, the concept of
      attractiveness was empirically defined with a group of prescription opioid
      abusers and experts in opioid abuse using a process called Concept Mapping. Abuse
      liability consisted of two components: factors intrinsic to the drug formulation
      (e.g., speed of onset, duration) and factors extrinsic to drug formulation (e.g.,
      availability, availability of alternatives, cost). A 17-item Opioid
      Attractiveness Scale (OAS) was constructed, focusing on factors intrinsic to the
      drug product. RESULTS: A total of 144 individuals participated in tests of
      validity and reliability. Internal consistency was excellent (Cronbach's alpha =
      0.85-0.94). Drug rankings based on OAS scores achieved good inter-rater agreement
      (Kendall's W 0.37, p < 0.001). Agreement on drug OAS scores between the
      developmental sample and a confirmation sample was good (IntraClass Correlations
      [ICC] of 0.65-0.69). Global ratings of overall attractiveness of the 14 selected
      opioid products by substance abuse counselors corresponded with the rankings
      based on OAS ratings of the abuser group. Finally, substance abuse counselors
      completed the OAS, yielding a high level of correspondence with ratings by the
      abuser group (ICC = 0.83, p = 0.002). The OAS differentiated attractiveness among
      14 selected pharmaceutical opioid products. OxyContin, Dilaudid, and Percocet
      were ranked highest (most attractive); Talwin NX and Duragesic were ranked lowest
      (least attractive). CONCLUSION: An initial examination of the psychometric
      properties of the OAS suggests that it is a valid and reliable scale. The OAS may
      be useful in providing important guidance on product features that are attractive
      to potential abusers.

PMID- 16457714
TI  - Fas ligand expression in human and mouse cancer cell lines; a caveat on over
      reliance on mRNA data.
AB  - BACKGROUND: During carcinogenesis, tumors develop multiple mechanisms for evading
      the immune response, including upregulation of Fas ligand (FasL/CD95L)
      expression. Expression of FasL may help to maintain tumor cells in a state of
      immune privilege by inducing apoptosis of anti-tumor immune effector cells.
      Recently this idea has been challenged by studies reporting that tumor cells of
      varying origin do not express FasL. In the present study, we aimed to
      comprehensively characterize FasL expression in tumors of both murine and human
      origin over a 72 hour time period. METHODS: RNA and protein was extracted from
      six human (SW620, HT29, SW480, KM12SM, HCT116, Jurkat) and three mouse (CMT93,
      CT26, B16F10) cancer cell lines at regular time intervals over a 72 hour time
      period. FasL expression was detected at the mRNA level by RT-PCR, using intron
      spanning primers, and at the protein level by Western Blotting and
      immunofluorescence, using a polyclonal FasL- specific antibody. RESULTS:
      Expression of FasL mRNA and protein was observed in all cell lines analysed.
      However, expression of FasL mRNA varied dramatically over time, with cells
      negative for FasL mRNA at many time points. In contrast, 8 of the 9 cell lines
      constitutively expressed FasL protein. Thus, cells can abundantly express FasL
      protein at times when FasL mRNA is absent. CONCLUSION: These findings demonstrate
      the importance of complete analysis of FasL expression by tumor cells in order to
      fully characterize its biological function and may help to resolve the
      discrepancies present in the literature regarding FasL expression and tumor
      immune privilege.

PMID- 16457715
TI  - Cutaneous metastasis to the face from colon adenocarcinoma. Case report.
AB  - BACKGROUND: Facial skin metastases from colorectal cancer are extremely rare and
      appear several years after resection of the primary tumour. They are an important
      finding, often being the first sign of metastasis from a previously treated colon
      cancer. CASE PRESENTATION: We describe a case of a 69 year old patient with
      cutaneous metastasis to the chin from a previously treated adenocarcinoma of the
      colon. The patient presented with dyspnoea, pleuritic pain and loss of weight. A
      chest x-ray revealed a right upper lobe mass of the lung which on subsequent
      surgical exploration proved to be metastatic from colorectal adenocarcinoma
      resected three years ago. During the postoperative course, a nodule was noted on
      the chin and excision biopsy revealed it was also a metastasis from the initial
      colorectal cancer. Palliative chemoradiotherapy was administered and the patient
      survived 8 months. CONCLUSION: High index of suspicion is necessary for the early
      detection of facial cutaneous metastases from colorectal cancer. The aim is to
      start treatment as soon as possible before widespread visceral metastases occur.
      Cutaneous metastases from colorectal cancer carry a better prognosis in
      comparison to those of other epithelial tumours.

PMID- 16457716
TI  - Pain in cancer. An outcome research project to evaluate the epidemiology, the
      quality and the effects of pain treatment in cancer patients.
AB  - BACKGROUND: Management of pain related to advanced or metastatic cancer, although
      the availability of several pharmacological and non-pharmacological interventions
      and the existence of well-known guidelines and protocols, is often difficult and
      inadequate. Evidence of the relative effectiveness of current options for
      treating cancer pain from comparative randomized studies is scanty. METHODS: In
      the context of a wider project, a multicenter, open label, prospective Outcome
      Research study will be launched in Italy in 2006 to investigate the epidemiology
      of cancer pain and of its treatments, the quality of analgesic-drug therapy and
      the effectiveness of alternative analgesic strategies in a large, prospective,
      unselected cohort of cancer patients using the state-of-the art of patient
      reported-outcomes. About 100 Italian centers will recruit 2500 patients with
      advanced/progressive/metastatic cancer with pain (related to the cancer disease)
      requiring analgesic treatments. Each center is expected to recruit 25 consecutive
      and eligible patients during the study inception period. Approximately two months
      will be allowed for subject recruitment and enrollment. Subject evaluation and
      follow-up will be for 3 months. The effect on outcomes of various therapeutic
      analgesic options administered by physicians, given the observational approach
      where patients are not assigned at random to different treatments, will be
      compared using the propensity score approach, allowing the adjustment for
      treatment selection bias. Later, after the launch of the observational study and
      on the basis of results, in specific subsamples of patients and in select centers
      of the network, a Randomized Controlled Trial will be carried out to formally
      compare the efficacy of alternative analgesic strategies, with particular
      emphasis on oral morphine (as comparator) and buprenorphine patch (as
      experimental arm). Results from the outcome (cohort) and experimental (Randomized
      Controlled Trial) studies will ensure both the external and internal validity.

PMID- 16457717
TI  - Household dyeing plants and traditional uses in some areas of Italy.
AB  - BACKGROUND: This paper reports the results of investigations carried out from
      1977 to today in some areas of Italy (Latium, Marche, Abruzzo and to a limited
      extent in Sardinia) concerning traditional uses of dyeing plants in the
      household. RESULTS: Twenty-nine plants are described, distributed in 23 families,
      and for each species the vernacular name, the way it is used and the locations of
      traditional use are given. Other plants used in the past in the above-mentioned
      regions are recalled. CONCLUSION: Among the new findings--not mentioned in
      previous literature, see references--is Muscari neglectum (purplish). Nowadays
      atavistic dye uses still persist only in Nule (Sardinia).

PMID- 16457718
TI  - Human hair genealogies and stem cell latency.
AB  - BACKGROUND: Stem cells divide to reproduce themselves and produce differentiated
      progeny. A fundamental problem in human biology has been the inability to measure
      how often stem cells divide. Although it is impossible to observe every division
      directly, one method for counting divisions is to count replication errors; the
      greater the number of divisions, the greater the numbers of errors. Stem cells
      with more divisions should produce progeny with more replication errors. METHODS:
      To test this approach, epigenetic errors (methylation) in CpG-rich molecular
      clocks were measured from human hairs. Hairs exhibit growth and replacement
      cycles and "new" hairs physically reappear even on "old" heads. Errors may
      accumulate in long-lived stem cells, or in their differentiated progeny that are
      eventually shed. RESULTS: Average hair errors increased until two years of age,
      and then were constant despite decades of replacement, consistent with new hairs
      arising from infrequently dividing bulge stem cells. Errors were significantly
      more frequent in longer hairs, consistent with long-lived but eventually shed
      mitotic follicle cells. CONCLUSION: Constant average hair methylation regardless
      of age contrasts with the age-related methylation observed in human intestine,
      suggesting that error accumulation and therefore stem cell latency differs among
      tissues. Epigenetic molecular clocks imply similar mitotic ages for hairs on
      young and old human heads, consistent with a restart with each new hair, and with
      genealogies surreptitiously written within somatic cell genomes.

PMID- 16457719
TI  - Growth of etiolated barley plants in weak static and 50 Hz electromagnetic fields
      tuned to calcium ion cyclotron resonance.
AB  - BACKGROUND: The effects of weak magnetic and electromagnetic fields in biology
      have been intensively studied on animals, microorganisms and humans, but
      comparably less on plants. Perception mechanisms were attributed originally to
      ferrimagnetism, but later discoveries required additional explanations like the
      "radical pair mechanism" and the "Ion cyclotron resonance" (ICR), primarily
      considered by Liboff. The latter predicts effects by small ions involved in
      biological processes, that occur in definite frequency- and intensity ranges
      ("windows") of simultaneously impacting magnetic and electromagnetic fields
      related by a linear equation, which meanwhile is proven by a number of in vivo
      and in vitro experiments. METHODS: Barley seedlings (Hordeum vulgare, L. var.
      Steffi) were grown in the dark for 5 and 6 days under static magnetic and 50 Hz
      electromagnetic fields matching the ICR conditions of Ca2+. Control cultures were
      grown under normal geomagnetic conditions, not matching this ICR. Morphology,
      pigmentation and long-term development of the adult plants were subsequently
      investigated. RESULTS: The shoots of plants exposed to Ca2+-ICR exposed grew 15
      20% shorter compared to the controls, the plant weight was 10-12% lower, and they
      had longer coleoptiles that were adhering stronger to the primary leaf tissue.
      The total pigment contents of protochlorophyllide (PChlide) and carotenoids were
      significantly decreased. The rate of PChlide regeneration after light irradiation
      was reduced for the Ca2+-ICR exposed plants, also the Shibata shift was slightly
      delayed. Even a longer subsequent natural growing phase without any additional
      fields could only partially eliminate these effects: the plants initially exposed
      to Ca2+-ICR were still significantly shorter and had a lower chlorophyll (a+b)
      content compared to the controls. A continued cultivation and observation of the
      adult plants under natural conditions without any artificial electromagnetic
      fields showed a retardation of the originally Ca2+-ICR exposed plants compared to
      control cultures lasting several weeks, with an increased tendency for
      dehydration. CONCLUSION: A direct influence of the applied MF and EMF is
      discussed affecting Ca2+ levels via the ICR mechanism. It influences the
      available Ca2+ and thereby regulatory processes. Theoretical considerations on
      molecular level focus on ionic interactions with water related to models using
      quantum electrodynamics.

PMID- 16457720
TI  - The XVI International Conference on AIDS: the place to be!
AB  - This editorial represents a plea to retrovirologists to attend the XVI
      International Conference on AIDS that will take place in Toronto, Canada between
      August 13-18, 2006. In short, it is vital that politicians and opinion leaders
      understand that basic scientists are no less committed to the worldwide battle
      against HIV than community activists or non-basic scientists, and the best way to
      demonstrate this is by showing up.

PMID- 16457721
TI  - Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation
      of DAF-16/FOXO to the cytoplasm.
AB  - BACKGROUND: The provision of stress resistance diverts resources from development
      and reproduction and must therefore be tightly regulated. In Caenorhabditis
      elegans, the switch to increased stress resistance to promote survival through
      periods of starvation is regulated by the DAF-16/FOXO transcription factor.
      Reduction-of-function mutations in AGE-1, the C. elegans Class IA
      phosphoinositide 3-kinase (PI3K), increase lifespan and stress resistance in a
      daf-16 dependent manner. Class IA PI3Ks downregulate FOXOs by inducing their
      translocation to the cytoplasm. However, the circumstances under which AGE-1 is
      normally activated are unclear. To address this question we used C. elegans first
      stage larvae (L1s), which when starved enter a developmentally-arrested diapause
      stage until food is encountered. RESULTS: We find that in L1s both starvation and
      daf-16 are necessary to confer resistance to oxidative stress in the form of
      hydrogen peroxide. Accordingly, DAF-16 is localised to cell nuclei after short
      term starvation. However, after long-term starvation, DAF-16 unexpectedly
      translocates to the cytoplasm. This translocation requires functional age-1. H2O2
      treatment can replicate the translocation and induce generation of the AGE-1
      product PIP3. Because feeding reduces to zero in ageing adult C. elegans, these
      animals may also undergo long-term starvation. Consistent with our observation in
      L1s, DAF-16 also translocates to the cytoplasm in old adult worms in an age-1
      dependent manner. CONCLUSION: DAF-16 is activated in the starved L1 diapause. The
      translocation of DAF-16 to the cytoplasm after long-term starvation may be a
      feedback mechanism that prevents excessive expenditure on stress resistance. H2O2
      is a candidate second messenger in this feedback mechanism. The lack of this
      response in age-1(hx546) mutants suggests a novel mechanism by which this
      mutation increases longevity.

PMID- 16457722
TI  - An advanced expiratory circuit for the recovery of perfluorocarbon liquid from
      non-saturated perfluorocarbon vapour during partial liquid ventilation: an
      experimental model.
AB  - BACKGROUND: The loss of perfluorocarbon (PFC) vapour in the expired gases during
      partial liquid ventilation should be minimized both to prevent perfluorocarbon
      vapour entering the atmosphere and to re-use the recovered PFC liquid. Using a
      substantially modified design of our previously described condenser, we aimed to
      determine how much perfluorocarbon liquid could be recovered from gases
      containing PFC and water vapour, at concentrations found during partial liquid
      ventilation, and to determine if the amount recovered differed with background
      flow rate (at flow rates suitable for use in neonates). METHODS: The expiratory
      line of a standard ventilator circuit set-up was mimicked, with the addition of
      two condensers. Perfluorocarbon (30 mL of FC-77) and water vapour, at
      concentrations found during partial liquid ventilation, were passed through the
      circuit at a number of flow rates and the percentage recovery of the liquids
      measured. RESULTS: From 14.2 mL (47%) to 27.3 mL (91%) of the infused 30 mL of FC
      77 was recovered at the flow rates studied. Significantly higher FC-77 recovery
      was obtained at lower flow rates (ANOVA with Bonferroni's multiple comparison
      test, p < 0.0001). As a percentage of the theoretical maximum recovery, 64 to 95%
      of the FC-77 was recovered. Statistically significantly less FC-77 was recovered
      at 5 Lmin(-1) (ANOVA with Bonferroni's multiple comparison test, p < 0.0001).
      Amounts of perfluorocarbon vapour recovered were 47%, 50%, 81% and 91% at flow
      rates of 10, 5, 2 and 1 Lmin(-1), respectively. CONCLUSION: Using two condensers
      in series 47% to 91% of perfluorocarbon liquid can be recovered, from gases
      containing perfluorocarbon and water vapour, at concentrations found during
      partial liquid ventilation.

PMID- 16457723
TI  - An immune reaction may be necessary for cancer development.
AB  - BACKGROUND: The hypothesis of immunosurveillance suggests that new neoplasms
      arise very frequently, but most are destroyed almost at their inception by an
      immune response. Its correctness has been debated for many years. In its support,
      it has been shown that the incidences of many tumor types, though apparently not
      all, tend to be increased in immunodeficient animals or humans, but this
      observation does not end the debate. ALTERNATIVE MODEL: There is an alternative
      to the surveillance hypothesis; numerous studies have shown that the effect of an
      immune reaction on a tumor is biphasic. For each tumor, there is some
      quantitatively low level of immune reaction that, relative to no reaction, is
      facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum
      level of this facilitating reaction may often be less than the level of immunity
      that the tumor might engender in a normal subject. CONCLUSION: The failure of a
      tumor to grow as well in the normal as it does in the immunosuppressed host is
      probably not caused by a lack of tumor-cell killing in the suppressed host.
      Instead, the higher level of immune response in a normal animal, even if it does
      not rise to tumor-inhibitory levels, probably gives less positive support to
      tumor growth. This seems more than a semantic distinction.

PMID- 16457724
TI  - Ecologists can enable communities to implement malaria vector control in Africa.
AB  - BACKGROUND: Integrated vector management (IVM) for malaria control requires
      ecological skills that are very scarce and rarely applied in Africa today.
      Partnerships between communities and academic ecologists can address this
      capacity deficit, modernize the evidence base for such approaches and enable
      future scale up. METHODS: Community-based IVM programmes were initiated in two
      contrasting settings. On Rusinga Island, Western Kenya, community outreach to a
      marginalized rural community was achieved by University of Nairobi through a
      community-based organization. In Dar es Salaam, Tanzania, Ilala Municipality
      established an IVM programme at grassroots level, which was subsequently upgraded
      and expanded into a pilot scale Urban Malaria Control Programme with support from
      national academic institutes. RESULTS: Both programmes now access relevant
      expertise, funding and policy makers while the academic partners benefit from
      direct experience of community-based implementation and operational research
      opportunities. The communities now access up-to-date malaria-related knowledge
      and skills for translation into local action. Similarly, the academic partners
      have acquired better understanding of community needs and how to address them.
      CONCLUSION: Until sufficient evidence is provided, community-based IVM remains an
      operational research activity. Researchers can never directly support every
      community in Africa so community-based IVM strategies and tactics will need to be
      incorporated into undergraduate teaching programmes to generate sufficient
      numbers of practitioners for national scale programmes. Academic ecologists at
      African institutions are uniquely positioned to enable the application of
      practical environmental and entomological skills for malaria control by
      communities at grassroots level and should be supported to fulfil this neglected
      role.

PMID- 16457725
TI  - Two unrelated putative membrane-bound progestin receptors, progesterone membrane
      receptor component 1 (PGMRC1) and membrane progestin receptor (mPR) beta, are
      expressed in the rainbow trout oocyte and exhibit similar ovarian expression
      patterns.
AB  - BACKGROUND: In lower vertebrates, steroid-induced oocyte maturation is considered
      to involve membrane-bound progestin receptors. Two totally distinct classes of
      putative membrane-bound progestin receptors have been reported in vertebrates. A
      first class of receptors, now termed progesterone membrane receptor component
      (PGMRC; subtypes 1 and 2) has been studied since 1996 but never studied in a fish
      species nor in the oocyte of any animal species. A second class of receptors,
      termed membrane progestin receptors (mPR; subtypes alpha, beta and gamma), was
      recently described in vertebrates and implicated in the progestin-initiated
      induction of oocyte maturation in fish. METHODS: In the present study, we report
      the characterization of the full coding sequence of rainbow trout PGMRC1 and mPR
      beta cDNAs, their tissue distribution, their ovarian expression profiles during
      oogenesis, their hormonal regulation in the full grown ovary and the in situ
      localization of PGMRC1 mRNA in the ovary. RESULTS: Our results clearly show, for
      the first time in any animal species, that rainbow trout PGMRC1 mRNA is present
      in the oocyte and has a strong expression in ovarian tissue. In addition, we show
      that both mPR beta and PGMRC1, two members of distinct membrane-bound progestin
      receptor classes, exhibit highly similar ovarian expression profiles during the
      reproductive cycle with maximum levels during vitellogenesis and a down
      expression during late vitellogenesis. In addition, the mRNA abundance of both
      genes is not increased after in vitro hormonal stimulation of full grown
      follicles by maturation inducing hormones. CONCLUSION: Together, our findings
      suggest that PGMRC1 is a new possible participant in the progestin-induced oocyte
      maturation in fish. However, its participation in the process of oocyte
      maturation, which remains to be confirmed, would occur at post-transcriptional
      levels.

PMID- 16457726
TI  - Rhodamine-RCA in vivo labeling guided laser capture microdissection of cancer
      functional angiogenic vessels in a murine squamous cell carcinoma mouse model.
AB  - BACKGROUND: Cancer growth, invasion and metastasis are highly related to tumor
      associated neovasculature. The presence and progression of endothelial cells in
      cancer is chaotic, unorganized, and angiogenic vessels are less functional.
      Therefore, not all markers appearing on the chaotic endothelial cells are
      accessible if a drug is given through the vascular route. Identifying endothelial
      cell markers from functional cancer angiogenic vessels will indicate the
      accessibility and potential efficacy of vascular targeted therapies. RESULTS: In
      order to quickly and effectively identify endothelial cell markers on the
      functional and accessible tumor vessels, we developed a novel technique by which
      tumor angiogenic vessels are labeled in vivo followed by Laser Capture
      Microdissection of microscopically isolated endothelial cells for genomic
      screening. Female C3H mice (N = 5) with established SCCVII tumors were treated
      with Rhodamine-RCA lectin by tail vein injection, and after fluorescence
      microscopy showed a successful vasculature staining, LCM was then performed on
      frozen section tissue using the PixCell II instrument with CapSure HS caps under
      the Rhodamine filter. By this approach, the fluorescent angiogenic endothelial
      cells were successfully picked up. As a result, the total RNA concentration
      increased from an average of 33.4 ng/ul +/- 24.3 (mean +/- S.D.) to 1913.4 ng/ul
      +/- 164. Relatively pure RNA was retrieved from both endothelial and epithelial
      cells as indicated by the 260/280 ratios (range 2.22-2.47). RT-PCR and gene
      electrophoresis successfully detected CD31 and Beta-Actin molecules with minimal
      Keratin 19 expression, which served as the negative control. CONCLUSION: Our
      present study demonstrates that in vivo Rhodamine RCA angiogenic vessel labeling
      provided a practical approach to effectively guide functional endothelial cell
      isolation by laser capture microdissection with fluorescent microscopy, resulting
      in high quality RNA and pure samples of endothelial cells pooled for detecting
      genomic expression.

PMID- 16457727
TI  - Prognostic significance of pathological response after neoadjuvant chemotherapy
      or chemoradiation for locally advanced cervical carcinoma.
AB  - BACKGROUND: Cisplatin-based chemoradiation is the standard of care for locally
      advanced cervical cancer patients; however, neoadjuvant modalities are currently
      being tested. Neoadjuvant studies in several tumor types have underscored the
      prognostic significance of pathological response for survival; however there is a
      paucity of studies in cervical cancer investigating this issue. METHODS: Four
      cohorts of patients with locally advanced cervical carcinoma (stages IB2-IIIB);
      included prospectively in phase II protocols of either neoadjuvant chemotherapy
      with 1) cisplatin-gemcitabine, 2) oxaliplatin-gemcitabine, 3) carboplatin
      paclitaxel or 4) chemoradiation with cisplatin or cisplatin-gemcitabine followed
      by radical hysterectomy were analyzed for pathological response and survival.
      RESULTS: One-hundred and fifty three (86%) of the 178 patients treated within
      these trials, underwent radical hysterectomy and were analyzed. Overall, the mean
      age was 44.7 and almost two-thirds were FIGO stage IIB. Pathological response
      rates were as follows: Complete (pCR) in 60 cases (39.2%), Near-complete (p-Near
      CR) in 24 (15.6 %) and partial (pPR) in 69 cases (45.1%). A higher proportion
      rate of pCR was observed in patients treated with chemoradiotherapy (with
      cisplatin [19/40, 47.5%]; or with cisplatin-gemcitabine [24/41, 58.5%] compared
      with patients receiving only chemotherapy, 6/23 (26%), 3/8 (37.5%) and 8/41
      (19.5%) for cisplatin-gemcitabine, oxaliplatin-gemcitabine and carboplatin
      paclitaxel respectively [p = 0.0001]). A total of 29 relapses (18.9%) were
      documented. The pathological response was the only factor influencing on relapse,
      since only 4/60 (6.6%) patients with pCR relapsed, compared with 25/93 (26.8%)
      patients with viable tumor, either pNear-CR or pPR (p = 0.001). Overall survival
      was 98.3% in patients with pCR versus 83% for patients with either pNear-CR or
      pPR (p = 0.009). CONCLUSION: Complete pathological response but no Near-complete
      and partial responses is associated with longer survival in cervical cancer
      patients treated with neoadjuvant chemotherapy or chemoradiotherapy.

PMID- 16457728
TI  - The effect of inpatient rehabilitation programmes on quality of life in patients
      with cystic fibrosis: a multi-center study.
AB  - BACKGROUND: Disease-specific, multimodal inpatient rehabilitation programmes are
      designed to improve the physical, emotional, and social functioning of patients
      with cystic fibrosis (CF). This study investigates the effects of a 4-week
      inpatient rehabilitation program on health-related quality of life (QL). METHODS:
      84 German patients with CF (16-62 years of age, FEV1 mean 52.9% of the
      predicted), participating in an inpatient rehabilitation programme, completed the
      Questions on Life Satisfaction-Modules (FLZM) at the beginning and one month
      after the end of intervention. The FLZM allows the multi-dimensional evaluation
      of subjectively perceived satisfaction with general and health-specific life
      domains. In addition, medical parameters (FEV1, Body Mass Index) and socio
      demographic data were registered. RESULTS: Compared to the baseline scores, after
      rehabilitation, participants were significantly more satisfied with general,
      health-related, and CF-related aspects of their lives. Specifically, improvement
      was noted in the following items: breathing difficulties/cough, sleep,
      integration of therapy into daily routine, leisure activities, general health
      perception, physical condition and being free from anxiety. CONCLUSION:
      Comprehensive inpatient rehabilitation programmes are a promising strategy to
      improve the quality of life of adolescent and adult CF-patients.

PMID- 16457729
TI  - A suboptimal 5' splice site downstream of HIV-1 splice site A1 is required for
      unspliced viral mRNA accumulation and efficient virus replication.
AB  - BACKGROUND: Inefficient alternative splicing of the human immunodeficiency virus
      type 1(HIV-1) primary RNA transcript results in greater than half of all viral
      mRNA remaining unspliced. Regulation of HIV-1 alternative splicing occurs through
      the presence of suboptimal viral 5' and 3' splice sites (5' and 3'ss), which are
      positively regulated by exonic splicing enhancers (ESE) and negatively regulated
      by exonic splicing silencers (ESS) and intronic splicing silencers (ISS). We
      previously showed that splicing at HIV-1 3'ss A2 is repressed by ESSV and
      enhanced by the downstream 5'ss D3 signal. Disruption of ESSV results in
      increased vpr mRNA accumulation and exon 3 inclusion, decreased accumulation of
      unspliced viral mRNA, and decreased virus production. RESULTS: Here we show that
      optimization of the 5'ss D2 signal results in increased splicing at the upstream
      3'ss A1, increased inclusion of exon 2 into viral mRNA, decreased accumulation of
      unspliced viral mRNA, and decreased virus production. Virus production from the
      5'ss D2 and ESSV mutants was rescued by transient expression of HIV-1 Gag and
      Pol. We further show that the increased inclusion of either exon 2 or 3 does not
      significantly affect the stability of viral mRNA but does result in an increase
      and decrease, respectively, in HIV-1 mRNA levels. The changes in viral mRNA
      levels directly correlate with changes in tat mRNA levels observed upon increased
      inclusion of exon 2 or 3. CONCLUSION: These results demonstrate that splicing at
      HIV-1 3'ss A1 is regulated by the strength of the downstream 5'ss signal and that
      suboptimal splicing at 3'ss A1 is necessary for virus replication. Furthermore,
      the replication defective phenotype resulting from increased splicing at 3'ss A1
      is similar to the phenotype observed upon increased splicing at 3'ss A2. Further
      examination of the role of 5'ss D2 and D3 in the alternative splicing of 3'ss A1
      and A2, respectively, is necessary to delineate a role for non-coding exon
      inclusion in HIV-1 replication.

PMID- 16457731
TI  - Studies of the role of steroid hormone in the regulation of oocyte maturation in
      cattle.
AB  - BACKGROUND: The objective of this study was to investigate whether the steroid
      hormone(s) secreted from cumulus-oocyte complexes (COCs) is a prerequisite for
      bovine oocyte maturation and cumulus expansion using aminoglutethimide (AGT), a
      P450 cholesterol side-chain cleavage inhibitor. METHODS: In experiment 1, COCs
      were cultured in maturation medium with various concentrations of AGT for 22 h to
      determine the effective concentration of AGT to inhibit steroid hormone
      secretion, meiotic maturation and cumulus expansion. In experiment 2, COCs were
      cultured in conditioned medium (CM) and TCM-199 medium with or without 10 mM AGT
      to check whether steroid hormones secreted from COCs were responsible for oocyte
      maturation and cumulus expansion. Experiments 3 and 4 were carried out to
      determine whether exogenous progesterone or estradiol-17beta was able to overcome
      the inhibitory effects of AGT on oocytes maturation and cumulus expansion. COCs
      cultured in 10 mM AGT-containing medium supplemented with various concentrations
      of progesterone or estradiol-17beta for 22 h were examined for oocyte maturation
      and cumulus expansion. RESULTS: Experiment 1 showed that a concentration of 10 mM
      AGT in medium was sufficient to block steroid hormone secretion, oocyte
      maturation and cumulus expansion, and that these inhibitory effects were fully
      reversible. In experiment 2, the addition of 10 mM AGT to CM did not
      significantly prevent oocyte maturation and cumulus expansion, implying that CM
      contains the steroid hormone(s) secreted from COCs, which are closely associated
      with oocyte maturation and cumulus expansion. The results in experiments 3 and 4
      demonstrated that the addition of any concentration of progesterone or estradiol
      17beta in the medium did not reduce the inhibitory effects of AGT on oocyte
      maturation and cumulus expansion. CONCLUSION: Our results indicate that bovine
      oocytes surrounded by cumulus cells are prevented from maturation and cumulus
      expansion through the inhibition of steroid secretion due to AGT, and that these
      inhibitory effects of AGT on oocyte maturation and cumulus expansions can not be
      overcome by the addition of either progesterone or estradiol-17beta in the
      medium. These observations suggest that some steroid hormone(s) other than P4 and
      E2 secreted from bovine COCs is essential for their meiotic maturation and
      cumulus expansion.

PMID- 16457732
TI  - The proximal promoter region of mTert is sufficient to regulate telomerase
      activity in ES cells and transgenic animals.
AB  - BACKGROUND: The reverse transcriptase of telomerase (Tert) controls telomerase
      activity maintaining the end of linear chromosomes in eukaryotic cells.
      Telomerase function is highly active in undifferentiated multipotent stem cells,
      decreases with cell differentiation and is generally absent from most somatic
      cells in the adult. Its absence is responsible of telomeres shortening in such
      somatic cells. Using an in vivo transgenic model and an in vitro culture
      differentiation of adult stem cells, we examined the elements of the mouse Tert
      (mTert) promoter that control telomerase activity. RESULTS: Three constructs
      comprising 1, 2 or 5 kb of the mTert promoter sequence coupled to the coding
      sequence of the green fluorescent protein (EGFP) were electroporated into
      embryonic stem (ES) cells. Transformed ES cells were able to mimic the expected
      mTert expression, which was associated to green fluorescence. One and 5 kb
      promoter produced the higher expression of EGFP, on ES cells. When ES cells were
      allowed to differentiate to embryoid bodies and to other cell types, they lost
      gradually the expression of mTert-EGFP as consequence of differentiation. No
      differences were found among the three constructs analyzed. We then generated
      transgenic mice with the three constructs. Expression of the reporter gene was
      monitored by reverse transcription-PCR analysis and EGFP visualization. The mRNA
      expression of the three constructs was lower than the endogenous mTert, but
      mimicked the endogenous mTert transcription pattern; however, no fluorescent
      expression of EGFP was detected in adult tissues. EGFP expression of the three
      constructs was visualized at the blastocysts stage and in new ES cells generated
      from them; in the germinal ring of E13 dpc foetuses; in ES-like colonies and in
      germinal stem cells generated from neonatal and adult testis cells; and in
      neuroesferes generated from E14 dpc foetuses' brain cells. CONCLUSION: The 1 kb
      promoter upstream of the initiating ATG codon of mTert contains all the
      regulatory elements to control telomerase expression in ES cells during in vitro
      loss of pluripotency. The transgenic mouse lines generated represent an
      appropriate system to analyze the expression of mouse Tert gene under
      physiological condition and during establishment of stem cell lines generated
      from embryonic or adult tissues.

PMID- 16457734
TI  - Identification, cloning and functional characterization of novel beta-defensins
      in the rat (Rattus norvegicus).
AB  - BACKGROUND: Beta-defensins are small cationic peptides that exhibit broad
      spectrum antimicrobial properties. The majority of beta-defensins identified in
      humans are predominantly expressed in the male reproductive tract and have roles
      in non-immunological processes such as sperm maturation and capacitation.
      Characterization of novel defensins in the male reproductive tract can lead to
      increased understanding of their dual roles in immunity and sperm maturation.
      METHODS: In silico rat genomic analyses were used to identify novel beta
      defensins related to human defensins 118-123. RNAs isolated from male
      reproductive tract tissues of rat were reverse transcribed and PCR amplified
      using gene specific primers for defensins. PCR products were sequenced to confirm
      their identity. RT-PCR analysis was performed to analyze the tissue distribution,
      developmental expression and androgen regulation of these defensins. Recombinant
      defensins were tested against E. coli in a colony forming unit assay to analyze
      their antimicrobial activities. RESULTS: Novel beta-defensins, Defb21, Defb24,
      Defb27, Defb30 and Defb36 were identified in the rat male reproductive tract.
      Defb30 and Defb36 were the most restricted in expression, whereas the others were
      expressed in a variety of tissues including the female reproductive tract. Early
      onset of defensin expression was observed in the epididymides of 10-60 day old
      rats. Defb21-Defb36 expression in castrated rats was down regulated and
      maintained at normal levels in testosterone supplemented animals. DEFB24 and
      DEFB30 proteins showed potent dose and time dependent antibacterial activity.
      CONCLUSION: Rat Defb21, Defb24, Defb27, Defb30 and Defb36 are abundantly
      expressed in the male reproductive tract where they most likely protect against
      microbial invasion. They are developmentally regulated and androgen is required
      for full expression in the adult epididymis.

PMID- 16457735
TI  - Assessment of microfilarial loads in the skin of onchocerciasis patients after
      treatment with different regimens of doxycycline plus ivermectin.
AB  - BACKGROUND: Infection with the filarial nematode Onchocerca volvulus can lead to
      severe dermatitis, visual impairment, and ultimately blindness. Since the
      currently used drug, ivermectin does not have macrofilaricidal or strong
      permanent sterilising effects on the adult worm, more effective drugs are needed
      to complement the use of ivermectin alone. Wolbachia endosymbiotic bacteria in
      filariae have emerged as a new target for treatment with antibiotics which can
      lead to long -term sterilization of the adult female filariae. METHODS: In the
      Central Region of Ghana, 60 patients were recruited, allocated into four groups
      and treated with 200 mg doxycycline per day for 2 weeks, 4 weeks, 6 weeks
      respectively. Untreated patients served as controls. Some of the treated patients
      and the untreated controls were given 150 microg/kg ivermectin 8 months after the
      start of doxycycline treatment. RESULTS: A follow up study 18 months post
      treatment showed that when using doxycycline alone there was a significant
      reduction of microfilarial (mf) loads in patients treated for either 4 or 6
      weeks. However, there was no significant difference between the untreated
      controls and those given the 2 weeks regimen. Although no significant difference
      was demonstrated between the 4 and 6 weeks regimens, there was a trend observed,
      in that, microfilarial reduction appeared to have been greater following the 6
      weeks regimen. Twelve months after ivermectin (i.e. 20 months after doxycycline)
      treatment, 8 out of 11 ivermectin-alone treated patients were mf-positive. In
      contrast, 1 out of the 7 patients treated for 4 weeks with doxycycline and none
      of the 4 patients treated for 6 weeks doxycycline (who were available for re
      examination) were mf-positive after the combined treatment of doxycycline plus
      ivermectin treatment. CONCLUSION: Treatment of onchocerciasis with doxycycline
      for 4 weeks is effective. Nonetheless, mf reduction appeared to be greater in the
      6 weeks regimen. It is recommended that until further studies are carried out
      i.e. 4 weeks treatment with doxycycline is proven equivalent to the 6 weeks,
      selected groups of onchocerciasis patients should be treated for 6 weeks with
      doxycycline. As discussed earlier, this treatment should be accompanied by two
      doses of ivermectin.

PMID- 16457736
TI  - Complete association between a retroviral insertion in the tyrosinase gene and
      the recessive white mutation in chickens.
AB  - BACKGROUND: In chickens, three mutant alleles have been reported at the C locus,
      including the albino mutation, and the recessive white mutation, which is
      characterized by white plumage and pigmented eyes. The albino mutation was found
      to be a 6 bp deletion in the tyrosinase (TYR) gene. The present work describes an
      approach to identify the structural rearrangement in the TYR gene associated with
      the recessive white mutation. RESULTS: Molecular analysis of the chicken TYR gene
      has revealed a major structural difference (Restriction Fragment Length
      Polymorphism, RFLP) in the genomic DNA of the recessive white chicken. A major
      size difference of 7.7 kb was found in intron 4 of the TYR gene by long-range
      PCR. Molecular cloning and sequencing results showed the insertion of a complete
      avian retroviral sequence of the Avian Leukosis Virus (ALV) family. Several
      aberrant transcripts of the tyrosinase gene were found in 10 week old recessive
      white chickens but not in the homozygous wild type colored chicken. We
      established a rapid genotyping diagnostic test based on the discovery of this
      retroviral insertion. It shows that all homozygous carriers of this insertion had
      a white plumage in various chicken strains. Furthermore, it was possible to
      distinguish heterozygous carriers from homozygous normal chickens in a
      segregating line. CONCLUSION: In this study, we conclude that the insertion of a
      complete avian retroviral sequence in intron 4 of the tyrosinase gene is
      diagnostic of the recessive white mutation in chickens. This insertion causes
      aberrant transcripts lacking exon 5, and we propose that this insertion is the
      causal mutation for the recessive white allele in the chicken.

PMID- 16457738
TI  - [The skin].

PMID- 16457737
TI  - Effectiveness of skills-based training using the Drink-less package to increase
      family practitioner confidence in intervening for alcohol use disorders.
AB  - BACKGROUND: Misuse of alcohol is second only to tobacco as a leading cause of
      preventable death in Australia. There is an opportunity in family practice to
      detect problems and intervene with people at risk of alcohol-related harm before
      complications occur. However, family practitioners (FPs) report low levels of
      confidence in managing patients with drinking problems. The aim of this study was
      to determine whether the interactive training session using the 'Drink-less'
      package led to improvement in FPs' self-reported level of confidence in detecting
      and providing interventions for risky alcohol consumption. METHOD: FPs in urban
      and rural New South Wales were invited to training sessions in their local area.
      An introductory overview preceded a practical skills- based session, using the
      Drink-less package. Participants completed before and after evaluation forms.
      RESULTS: While 49% (CI 43-55) of the attending FPs indicated at baseline that
      they felt confident in identifying at-risk drinkers, this proportion rose to 90%
      (95% CI: 87-93) post-session, and they also reported increases in confidence from
      36% (95% CI: 31-41) to 90% in their ability to advise patients. Urban FPs
      reported lower levels of confidence than rural FPs, both pre- and post-session.
      CONCLUSION: Training sessions in the Drink-less intervention resulted in
      increased self-reported confidence in detection and brief intervention for
      alcohol problems. Further research is needed to determine the duration of this
      effect and its influence on practice behaviour.

PMID- 16457739
TI  - [Mutations in dynamin 2 cause dominant centronuclear myopathy].

PMID- 16457740
TI  - [The paraplegic mouse: a model with new perspectives for spinal cord injury
      research].

PMID- 16457741
TI  - [Lowering blood pressure permits limiting cerebral microangiopathy].

PMID- 16457742
TI  - [Neuro-anatomy of space processing].

PMID- 16457743
TI  - [Does our interglacial period have an analogue in the past?].

PMID- 16457744
TI  - [Implication of the lymphoid neogenesis process in chronic rejection].

PMID- 16457745
TI  - [T4-type bacteriophages: ubiquitous components of the "dark matter" of the
      biosphere].

PMID- 16457746
TI  - [RelA, a new player in the regulation of RelB activity].

PMID- 16457747
TI  - [Role of dopamine in Huntington's disease].

PMID- 16457748
TI  - [Congenital afibrinogenemia: focusing on molecular mechanisms controlling
      fibrinogen secretion].

PMID- 16457749
TI  - [A myosin that moves backwards].

PMID- 16457752
TI  - [The life of human hair follicle revealed].
AB  - The human hair follicle is a unique appendage which results from epithelio
      mesenchymal interactions initiated around the 3rd month of development. This
      appendage has a very complex structure, with a dermal compartment and an
      epithelial compartment. The dermal compartment comprises the connective tissue
      sheath and the dermal papilla, both of which are irrigated by microvessels. The
      epithelial compartment is made of highly replicating matrix cells giving rise to
      three concentrical domains, namely the outer root sheath, the inner root sheath
      and the hair shaft. The pigmentation unit, responsible for hair color, is made of
      fully active melanocytes located on top of the dermal papilla. Altogether a hair
      follicle contains more than 20 different cell types, engaged in different
      differentiation pathways and/or interacting with each other. This complex
      appendage has a unique behavior in mammals since, after a hair production phase,
      it involutes in place before entering a resting phase after which it renews
      itself under a cyclical but stochastic way, out of a double reservoir of
      pluripotent stem cells able to also regenerate epidermis. For yet unknown
      reasons, this well ordered process can be disturbed, provoking alopecia. The
      pigmentation unit also renews itself under a cyclical way, out of a melanocyte
      progenitor reservoir which progressively declines with time, provoking the hair
      whitening process. Finally, the shape of the hair shaft is programmed from the
      bulb. What makes this appendage unique and fascinating is its high degree of
      autonomy, its incredibly complex though stable structure, the number of different
      cell types interacting under an equilibrated way and its potential of
      regeneration. It represents a true paradigm of tissue homeostasis, exemplifying
      in a small living cylinder all the fundamental laws of cell-cell and tissue
      interactions. This life is revealed in this short synthesis.

PMID- 16457751
TI  - [Histology of skin and hair follicle].
AB  - The skin consists of an outer epidermis, the dermis, and the hypodermis. It
      includes nerves, blood vessels, glands and hair follicles. Epidermis is a
      continually renewing, stratified squamous epithelium. It is populated by
      keratinocytes (80 %) and dendritic cells (20 %) : melanocytes, Langerhans and
      Merkel cells. In standard histology, keratinocytes are arranged in layers that
      represent different stages of their differentiation while melanocytes and
      Langerhans cells appear as clear cells respectively between the basal and the
      supra-basal cells of epidermis. The Merkel cells cannot be clearly identified.
      Dendritic processes of the dendritic cells can only be recognized by
      immunocytochemistry. At the dermal-epidermal junction, a PAS reactive basement
      membrane follows the contour of the basal cells. Dermis consists of collagenous
      and elastic fibers embedded into an amorphous ground substance. Fibroblasts,
      macrophages, mast cells and lymphocytes are its resident cells. Hypodermis is
      composed of adipocyte lobules defined by fibrous connective tissue septa. Hair
      follicle consists of 3 parts : the lower portion, from the base of the follicle
      including hair bulb to the insertion of the arrector pili muscle or buldge ; the
      isthmus, from the insertion of the arrector pili to the entrance of the sebaceous
      duct, and the infundibulum, from the entrance of the sebaceous duct to the
      follicular orifice. The lower portion is composed of the dermal hair papilla, the
      hair matrix, the hair, and the inner and the outer root sheaths. The hair matrix
      cells within hair bulb give rise to the hair and to the inner root sheath. With
      the electron microscope, one can obtain a more detailed view of the
      characteristic skin structures. Much of them can now be explained in terms of
      function and in many instances, in correlation with its biochemical composition.
      An attempt has been made in this paper to precisely give the location of
      molecules that are relevant in basic skin functions and understanding of auto
      immune and genetic diseases.

PMID- 16457753
TI  - [Langerhans cells].
AB  - Epidermal Langerhans cells, a constituent of the skin immune system, have a
      spectrum of different functions with implications that extend far beyond the
      skin. They have the potential to internalize particulate agents and
      macromolecules, and display migratory properties that endow them with the unique
      capacity to journey between skin and draining lymph nodes where they encounter
      antigen-specific T lymphocytes. In addition, LC are considered to play a pivotal
      role in infectious disease such as Aids, allergy, chronic inflammatory reactions,
      tumor rejections or transplantation. Herein, we will review the features of
      Langerhans cells, emphasizing characteristics representative of their life-cycle
      stages that occur within the skin.

PMID- 16457754
TI  - [Innate immunity: cutaneous expression of Toll-like receptors].
AB  - Toll receptors were first identified as an essential molecule for embryonic
      patterning in Drosophila and were subsequently shown to be a key in antibacterial
      and antifungal immunity in adult flies. Toll receptors have been conserved
      throughout evolution. In mammals, TLRs have been implicated in both inflammatory
      responses and innate host defense to pathogens. The 11 different TLRs recognize
      conserved molecular patterns of microbial pathogens termed pathogen-specific
      molecular patterns (PAMPs), that permit to confer responsiveness to a wide
      variety of pathogens. Endogenous ligands are also able to activate TLRs. All
      adult tissue is capable to express at least one of member of TLR family, but a
      largest repertoire of TLRs is found in tissues exposed to the external
      environment. The TLR activation induce the NF-kappaB translocation to the nucleus
      and cytokine secretion. Since the primary function of skin is to provide an
      effective barrier against outside agression, it is likely that keratinocytes may
      play a role in a rapid and efficient host defence system, and the fact that
      keratinocytes are capable of expressing a wide variety of TLRs is subsequently
      not surprising.

PMID- 16457755
TI  - [Innate antimicrobial peptides in the skin].
AB  - Human skin is always in contact with the environment and is covered with a
      characteristic microflora, but it is usually not infected. Although desquamation
      and secretion of mucus lead to a permanent renewal of these body surfaces and
      simultaneous elimination of microorganisms adhering to these layers, another
      reason for this natural resistance might be the existence of a "chemical barrier"
      consisting in constitutively and inducibly produced antimicrobial peptides and
      proteins (AMPs), which include some ss-defensins, RNase 7, the S100-protein
      psoriasin and the cathelicidin LL-37. Most of these AMPs can be induced in vitro
      in epithelial cells by proinflammatory cytokines or bacteria. In vivo, AMPs are
      mainly expressed in uppermost and differentiated parts of inflammatory lesions
      and wounds, but some are also focally expressed in skin in the absence of
      inflammation, suggesting that apart from inflammatory mediators, also non
      inflammatory stimuli of endogenous and/or exogenous origin can stimulate AMP
      synthesis. Increased levels of AMPs in psoriatic lesions may explain why
      psoriasis patients rarely suffer from skin infections. Further, an increased
      infection rate in atopic dermatitis patients could be the consequence of
      decreased levels of AMPs in atopic lesions. These observations may indicate an
      important role of the "chemical skin barrier" in prevention of skin infection and
      suggest that artificial stimulation of this system, without inflammation, would
      be beneficial as "immune stimulus".

PMID- 16457756
TI  - [Allergic contact dermatitis: how to re-induce tolerance?].
AB  - Allergic contact dermatitis (ACD) is a skin inflammatory disease mediated by
      activation of CD8+ cytotoxic T cells specific for haptens in contact with the
      skin. CD4+ T cells behave as both regulatory and tolerogenic cells since they
      down-regulate the skin inflammation in patients with ACD (regulation) and prevent
      the development of eczema (tolerance) in normal individuals. Thus, ACD
      corresponds to a breakdown of immune tolerance to haptens in contact with the
      skin. Several regulatory CD4+ T cell subsets (Treg), especially CD4+CD25+ natural
      Treg cells, are involved in immunological tolerance and regulation to haptens
      through the production of the immunosuppressive cytokines IL-10 and TGF-beta.
      Ongoing strategies to re-induce immune tolerance to haptens in patients with
      eczema include improvement of existing methods of tolerance induction (oral
      tolerance, low dose tolerance, allergen-specific immunotherapy, UV-induced
      tolerance) as well as development of new drugs able to activate IL-10 producing
      Treg cells in vivo. Ongoing and future progress in this area will open up new
      avenues for treatment of eczema and more generally autoimmune and allergic
      diseases resulting from a breakdown of tolerance to autoantigens and allergens,
      respectively.

PMID- 16457757
TI  - [Psoriasis: evolution and revolution].
AB  - Psoriasis is a model disease in dermatology. It is a common disease that affects
      at least 2 to 3 % of the population. It is an illness characterized by an
      excessive reaction of the skin, in term of proinflammatory cytokines release, to
      no specific attacks: these attacks can be immunological, mechanical, metabolic,
      drug-induced or psychological. This excessive reaction is characterized by
      epidermal proliferation combined with incomplete terminal differentiation, as
      well as an inflammatory response responsible for the chronic nature of the
      lesions. The way to understand psoriasis is therefore to reach a better
      appreciation of the messages that enable the skin cells to initiate an
      inflammatory response, and by better understanding the way in which the
      inflammatory cells responsible for innate and acquired immune responses are
      capable of bringing about proliferation and abnormal epidermal differentiation.
      Taking an interest in psoriasis is therefore taking an interest in all facets of
      skin physiology and in all the ways the skin reacts to attacks from the
      environment. Every year for more than thirty years, more than 300 publications
      have endeavoured to explore one aspect or another of psoriasis from a clinical,
      epidemiological, physiopathological or therapeutic point of view. There is no new
      technique for observing the skin that has not been immediately applied to the
      study of psoriasis - which is privileged to enjoy the reflected progress made in
      dermatology. Nor has psoriasis remained untouched by whims of fashion, all manner
      of scenarios having been suggested to explain it, right from a scarring disease
      to an autoimmune illness through a genetic or psychosomatic disorder. Psoriasis
      is at the origin of a medical revolution mounted to supplement and enhance the
      effectiveness of evidence-based medicine ; it is the "patient-centred medicine".
      Psoriasis only exceptionally jeopardizes life. Conversely, it is a disease that
      does affect quality of life. The patient alone must be the judge of his or her
      quality of life, and it is therefore up to the patient, not the doctor, to gauge
      the severity of psoriasis and hence decide on reasonable therapeutic indications.
      Psoriasis, then, cannot be treated without placing the patient, not the illness,
      at the centre of therapeutic negotiations. The 20th century has seen the disease
      targeted by boundless efforts ; the 21st century will see the development of
      medical techniques that allow the patient, in all its complexity, to be
      positioned at the centre of therapeutic efforts. This revolution began in
      dermatology, centring around psoriasis, and is spreading progressively to all
      chronic disorders and all disciplines. New quite interesting therapeutic weapons
      are available from a few months making possible to better adjust the therapeutic
      strategies of psoriasis to the patients needs but they are expensive opening
      again the debates on the limit of the social solidarity.

PMID- 16457758
TI  - [How to model the events in cutaneous fibrosis?].
AB  - Skin fibrosis is classically seen as the consequence of chronic inflammation and
      altered healing response that is characterized by the differentiation of
      fibroblasts into secretory myofibroblasts and accumulation of connective tissue.
      Although fibrosis severely affects organ function and causes esthetic defects, no
      effective therapy is currently available to attenuate the fibrogenic process
      probably because the fibrogenic process is more complex than previously thought.
      Indeed, it might involve several interacting and mutually dependent cell types
      (fibroblasts, keratinocytes, endothelial cells, inflammatory cells), numerous
      paracrine factors, bio-active molecules and micro-environmental stimuli (growth
      factors, vasoactive peptides, balance between pro- and anti-inflammatory
      cytokines, coagulation system, reactive oxygen species, extracellular matrix...).
      In this perspective, the traditional approach that model individual cell response
      in simple cell culture system is probably inadequate and too simplistic. This
      article reviews the new models used to study skin fibrosis in vitro, in
      organotypic culture systems and in vivo and examines how these different models
      might be used to identify new molecular pathways involved in fibrogenesis. The
      monolayer cultures allow the study of fibrogenic signals induced by a single
      factor on a single cell type. Isolation of cells from fibrotic tissue allows to
      define the fibrogenic differentiation acquired in vivo. The organotypic models
      allow cell to cell and cell to matrix interaction and the experimental models in
      pigs and mice allowed studies in integrated physiological systems. These various
      and complementary models would also provide new tools to develop and test new
      drugs and treatments.

PMID- 16457759
TI  - [Genotypic hypervariability of melanoma: a therapeutic challenge].
AB  - Cutaneous melanoma remains a management challenge. Melanoma is the leading cause
      of death from skin tumors worldwide. Melanoma progression is well defined in its
      clinical, histopathological and biological aspects, but the molecular mechanism
      involved and the genetic markers associated to metastatic dissemination are only
      beginning to be defined. The recent development of high-throughput technologies
      aimed at global molecular profiling of cancer is switching on the spotlight at
      previously unknown candidate genes involved in melanoma. Among those genes, BRAF
      is one of the most supposed to be of interest and targeted therapies are ongoing
      in clinical trials. In familial melanoma, germline mutations in two genes, CDKN2A
      and CDK4, that play a pivotal role in controlling cell cycle and division. It is
      hope that this better understanding of the biologic features of melanoma and the
      mechanisms underlying tumor-induced immunosuppression will lead to efficaceous
      targeted therapy.

PMID- 16457760
TI  - [Vaccine strategies against melanoma].
AB  - Melanoma incidence increases and conventional antitumor therapies are often
      ineffective, encouraging the design of novel therapies. Several lines of evidence
      support the notion of an immunological control of melanoma growth. Based on this
      information, active immunotherapy (vaccination) and adoptive immunotherapy trials
      (T cell therapy) were conducted in metastatic melanoma patients. The proof of
      principle of effective immunotherapy was brought up by pionnering trials using
      tumor infiltrated lymphocytes in lymphodepleted recipients or anti-CTLA4 Ab
      leading to tumor eradication but also autoimmune diseases. With the
      identification and characterization of tumor antigens recognized by cytotoxic T
      lymphocytes, the utilization of tumor rejection antigens along with adjuvants
      become available as tumor vaccines. The last five years have witnessed the
      emergence of dendritic cell based-vaccines that were efficient in priming and/or
      boosting T cell responses in normal volunteers and patients. This review
      highlights preclinical bases of cancer vaccines, their clinical development and
      discusses their limits. Correlations between immunomonitoring and tumor
      regressions await larger trials.

PMID- 16457761
TI  - [Epidermal necrolysis: mechanisms of keratinocyte apoptosis].
AB  - Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute and severe
      adverse reaction to drugs, characterized by the widespread destruction of the
      epithelium of the skin and mucous membranes. This destruction by massive
      apoptosis leads to a clinical pattern of epidermal necrolysis resembling second
      degree burns, with sheets of necrotic epidermis detached from the underlying
      dermis. The mechanisms of acute and extensive destruction of the skin are not yet
      fully understood. At the onset of the reaction blisters develop from the fluid
      that accumulates between the dead epidermis and the dermis. High concentrations
      of mononuclear cells are present in this blister fluid, principally CD8 T
      lymphocytes that may exhibit a drug specific MHC class I restricted cytotoxicity
      against autologous cells. The intervention of soluble mediators such as TNFalpha,
      perforin/granzyme, or Fas-Ligand may be necessary for amplifying the apoptosis of
      keratinocytes. A strong association between epidermal necrolysis to certain drugs
      and rare HLA-B genotypes suggests that direct interaction between these drugs and
      HLA-B molecules may initiate a reaction resembling the acute rejection of
      allogeneic epidermis.

PMID- 16457762
TI  - [Epidermotropic T cell lymphomas as models for tumor progression].
AB  - Primary cutaneous T cell lymphomas (CTCL) represent the most frequently occurring
      group of extra-nodal T cell lymphomas, originating from skin-homing memory T
      cells. Sezary syndrome (SS) is a leukemic variant of CTCL that presents with
      erythroderma, lymphadenopathies and presence of malignant T cells in peripheral
      blood. SS has an unfavourable prognosis, and is refractory to current treatments.
      Progress in understanding the pathogenesis and tumor progression of SS is
      limited. In the past few years, we have identified and reported several CTCL
      associated antigens, CD158k/KIR3DL2, CD85j/ILT2, and SC5/vimentin. KIR3DL2 is the
      first phenotypic marker of Sezary cells that can be used for the diagnostic and
      follow-up of Sezary syndrome. The SC5 antibody is the only monoclonal antibody
      reacting with vimentin on the surface of viable Sezary cells. CTCL are
      characterized by a predominance of Th2 cytokines. The recent suggestion that CTCL
      cells could be regulatory T (Tr) cells remains controversial. Gene expression
      studies suggest that in the future we may develop new diagnostic and prognostic
      tools, and identify subsets of patients who would benefit from more appropriate
      treatment protocols. Future challenges are to render tumor cells sensitive to
      apoptosis by inhibiting specific signalling pathways such as the constitutively
      activated NF-KB pathway, to identify specific surface kinase receptors and to
      develop specific inhibitors, to develop humanized monoclonal antibodies directed
      against tumor specific antigens, able to kill tumor cells via complement
      dependent and antibody-dependent cytotoxicity, and to stimulate innate immunity.

PMID- 16457763
TI  - [The "Moi-peau"].
AB  - To construct a coherent identity, humans must distinguish what belongs to the
      external, perceived world from what belongs to their own inner world and the
      inner world of other individuals. Based on the theory developed by S. Freud and
      on work by ethologists, a number of psychoanalysts (J. Bowlby, R.A. Spitz, D.W.
      Winnicott, etc.) have underlined the importance of early tactile exchanges with
      the mother if a child is to become an autonomous individual who feels secure
      within what he or she perceives to be sound and reliable mental and physical
      boundaries. More recently, other psychoanalysts (E. Bick, W.R. Bion, etc.) have
      studied the fantasized mental structures that form the limits between an
      individual's inner mental space and the external world (including other
      individuals). As part of this theoretical psychoanalytical movement, Didier
      Anzieu, a French psychoanalyst, started to develop the concept of the "Moi-peau"
      in 1974. The "Moi-peau" designates a fantasized reality that a child uses during
      its early development to represent itself as "me", based on its experience of the
      body surface. The child, enveloped in its mother's care, fantasizes of a skin
      shared with its mother: on one side the mother (the outer layer of the "Moi
      peau"), and on the other side the child (the inner layer of the "Moi-peau").
      These two layers must separate gradually if the child is to acquire its own me
      skin. D. Anzieu's work allowed dermatologists and other specialists, such as
      pediatricians, to focus on the quality of early tactile exchanges between a
      mother and her child, including the child with a chronic skin disorder. It also
      helped dermatologists to recognize patients with "borderline" states, which are
      particularly frequent in dermatology (ereutophobia, dysmorphophobia, tattooing,
      self-mutilation, artefacta dermatitis). These borderline patients are adults who,
      as a result of their mental conflicts, adopt defense mechanisms derived from both
      neurotic and psychotic functioning. Their complaints reflect difficulties with
      the solidity of their mental and physical limits: their real skin is
      metaphorically linked to the fantasized mental structure that delimits the
      individual mental space. Among other clinical characteristics, they have a
      "pathology of action" and frequently attack their own skin, paradoxically, in
      order to test the solidity and reliability of their own limits. Finally, D.
      Anzieu's work encouraged dermatologists to use psychotherapeutic approaches in
      parallel to classical dermatologic approaches, when necessary, and helped them
      better understand how psychoanalysts work with patients who have not yet acquired
      their own "Moi-peau". As a result, D. Anzieu was among the first to reconcile
      dermatologists and psychoanalysts.

PMID- 16457764
TI  - [Dreaming and schizophrenia: a common neurobiological background?].
AB  - Normal waking mentation is the outcome of the combined action of both
      electrophysiological and neurochemical antagonistic and complementary activating
      and inhibitory influences occurring mainly in the cerebral cortex. The chemical
      ones are supported principally by acetylcholine, and noradrenaline and serotonin,
      respectively. During rapid eye movement (REM) sleep, the monoaminergic silence -
      except dopaminergic ongoing activity - disrupts this equilibrium and seems to be
      responsible for disturbances of mental activity characteristic of dreaming. This
      imbalance could cause disconnectivity of cortical areas, failure of latent
      inhibition and possibly the concomitant prefrontal dorsolateral deactivation.
      Moreover, the decrease of prefrontal dopaminergic functioning could explain the
      loss of reflectiveness in this sleep stage. All these phenomena are also
      encountered in schizophrenia. The psychotic-like mentation of dreaming
      (hallucinations, delusions, bizarre thought processes) could result from the
      disinhibition of dopamine influence in the nucleus accumbens by the noradrenergic
      and serotonergic local silence and/or the lifting of glutamate influence from the
      prefrontal cortex and hippocampus. We hypothesize that, during REM sleep, the
      increase of dopamine and the decrease of glutamate release observed in nucleus
      accumbens reach the threshold values at which psychotic disturbances arise during
      wakefulness. Whatever the precise mechanism, it seems that the functional state
      of the prefrontal cortex and nucleus accumbens is the same during dreaming sleep
      stage and in schizophrenia. The convergent psychological, electrophysiological,
      tomographic, pharmacological and neurochemical criteria of REM sleep and
      schizophrenia suggest that this sleep stage could become a good neurobiological
      model of this psychiatric disease.

PMID- 16457765
TI  - [Scientific progress and new biological weapons].
AB  - The biological weapons are different from conventional weapons, because living
      germs hold an extraordinary and predictable potential for multiplication,
      propagation and genetic variation during their dissemination in a susceptible
      population. Only natural pathogens (1rst generation weapons) have been used in
      the past (smallpox virus, plague, anthrax, toxins...). However, new threats are
      emerging, due to the rapid progress of scientific knowledge and its exponential
      worldwide diffusion. It is possible to synthesize microorganisms from in silico
      sequences widely diffused on Internet (poliovirus, influenza...), thus resulting
      in the accessibility of very dangerous virus confined today in high-security
      laboratories (virus Ebola...). It is possible also to "improve" pathogens by
      genetic manipulations, becoming more resistant or virulent (2nd generation
      weapons). Finally, one can now create de novo new pathogens by molecular breeding
      (DNA shuffling), potentially highly dangerous for naive populations (3rd
      generation weapons). Making biological weapons does not require too much
      technological resources and appears accessible to terrorists, due to low cost and
      easy use. Although the destructive consequences are difficult to predict, the
      psychological and social damages should be considerable, because of the highly
      emotional burden in the population associated to the transgression by man of a
      taboo of life.

PMID- 16457766
TI  - [Canadian founders of haematopoietic stem cell research receive the Lasker
      Award].

PMID- 16457767
TI  - [Biomedical research practice and therapeutic practice: to whom does the human
      body belong?].
AB  - Who owns the human body? This issue has been formerly raised about the status of
      the slave. Today, it has become a prominent stake for when reflecting on
      biomedical research and healthcare practices. In our cultures, many answers may
      be given to this question : they are derived from philosophical or theological
      traditions ; they are borrowed from anthropological, sociological or
      psychological knowledge ; they may be formulated in a moral or political
      perspective. All of them give different insights and reveal one of the various
      dimensions of the question. When examining the status of the body and its
      relation to the human subject in the various stages of his/her life (including
      his/her death), one of the main difficulties is to deal with each of these
      answers and to understand how they meet and interact in the public debate.
      Another matter is related to the fact that law also plays a crucial role in the
      process of giving an answer to this question. In our book, A qui appartient le
      corps humain ? Medecine, politique et droit (Paris, Belles Lettres, 2004), Claire
      Crignon-De Oliveira and I have tried to deal with both difficulties. In this
      article, I focus on the meaning of the various law traditions. In western world,
      the laws are all derived, up to a certain extent, from the Roman tradition.
      Whether they have chosen to consider the human body as a property or to associate
      the body to the person, they have taken very different options. However, an
      examination of the ways laws are elaborated on this topic shows that these two
      conceptions can meet in unexpected manners and that lawmaking can give creative
      answers to both the problem of protecting the person and to the requirements of
      biomedical research and healthcare practices.

PMID- 16457768
TI  - [Scientific publication and therapeutic cloning now face Hwang mystification:
      more than a "Cloningate"].

PMID- 16457769
TI  - Multiple synergistic interactions between atovaquone and antifolates against
      Plasmodium falciparum in vitro: a rational basis for combination therapy.
AB  - The use of synergistic drug combinations for the treatment of drug-resistant
      malaria is a major strategy to slow the selection and spread of Plasmodium
      falciparum resistant strains. In order to investigate synergistic compounds, with
      different modes of action, as alternative candidates for combination therapy, we
      used standard in vitro P. falciparum cultures and an established synergy testing
      method to define interactions among dapsone (DDS), atovaquone (ATQ),
      chlorproguanil (CPG) and its triazine metabolite chlorcycloguanil (CCG). Strong
      synergy was observed in the combinations DDS/CCG and ATQ/CPG. Multiple
      combination of these drugs, DDS/CCG/CPG/ATQ also exhibited high synergy although
      not higher than that of either of the two drug combinations separately. The use
      of this triple combination DDS/CPG/ATQ, even without an increase in synergy over
      their double combinations, ATQ/CPG and DDS/CCG, would contribute towards slowing
      the selection pressure since these drugs act against different targets and would
      delay the selection of parasites resistant to the three drugs, extending the
      useful therapeutic life of these valuable compounds.

PMID- 16457770
TI  - Detection of low-molecular weight allergens resolved on two-dimensional
      electrophoresis with acid-urea polyacrylamide gel.
AB  - Two-dimensional electrophoresis with immobilized pH gradient (IPG) followed by
      acetic acid/urea-polyacrylamide gel electrophoresis (AU-PAGE) was developed for
      the detection of low-molecular weight food allergens. Wheat proteins were used to
      test the applicability of AU-PAGE for the analysis of food allergens. Isoelectric
      focusing (IEF) for first dimension was performed with IPG pH 3-10. AU-PAGE was
      performed as a second-dimensional electrophoresis and high resolution was
      obtained, especially for proteins below 15 kDa. For immunodetection, the proteins
      resolved on AU gel were transferred to a polyvinylidene difluoride membrane. The
      assembly of semidry electroblotting for AU gel was set reversed as for sodium
      dodecyl sulfate (SDS)-PAGE gel. The electroblotted membrane was immunolabeled
      with serum from a radio-allergosorbent test-positive individual for wheat to
      identify allergenic proteins. Protein spots strongly recognized by the patient's
      serum were chosen for further analysis. Mass spectrometry analysis revealed that
      these proteins were alpha-amylase/trypsin inhibitors and lipid transfer protein.
      The system developed in this study was shown to be useful as a standard protocol
      for the separation of low-molecular weight proteins. Moreover, the IPG strips on
      which IEF was performed could be used either for SDS-PAGE or AU-PAGE by only
      changing equilibrating conditions, allowing for a wide range of allergen
      analysis.

PMID- 16457772
TI  - Determination of dopamine in the presence of ascorbic acid by poly(styrene
      sulfonic acid) sodium salt/single-wall carbon nanotube film modified glassy
      carbon electrode.
AB  - In this study, poly(styrene sulfonic acid) sodium salt/single-wall carbon
      nanotube film was cast onto the surface of glassy carbon electrode and the
      electrochemical behavior of the modified electrode was investigated. The results
      show that the anodic peak current is proportional to the concentration of
      dopamine in the range of 1.6 x 10(-8)-6 x 10(-4) M. The detection limit is 8 x
      10(-9) M. The interference of ascorbic acid with the determination of dopamine
      could be eliminated due to the very distinct attracting interaction between
      dopamine cations and the negative poly(styrene sulfonic acid) sodium salt film in
      pH 7.0 phosphate-buffered saline solutions. The proposed method exhibits good
      sensitivity, selectivity, and reproducibility.

PMID- 16457771
TI  - Electrochemical detection of free 3-nitrotyrosine: application to microdialysis
      studies.
AB  - 3-Nitrotyrosine (3-NT) is formed by the reaction of peroxynitrite with either
      free or protein-bound tyrosine residues and has been proposed as a biomarker of
      oxidative stress caused by reactive nitrogen species. This study describes the
      development of an HPLC electrochemical detection assay for free 3-NT capable of
      measuring this metabolite at the very low (nanomolar) levels encountered
      physiologically. We employed a dual-cell coulometric approach in which 3-NT is
      first reduced at an upstream cell to 3-aminotyrosine, which itself is then
      oxidized at the downstream cell. The method was shown to be linear over the range
      of 1-500 nM (r = 0.999), with a detection limit (signal/noise ratio of 3) of 0.5
      nM (25 fmol on column). Ten consecutive injections of 2 and 20 nM 3-NT standards
      produced coefficients of variation of 5.88 and 1.87%, respectively. Validation of
      the identity of the 3-NT peak was confirmed by coelution with authentic standards
      and by the in vitro production of 3-NT by incubation of 3-morpholinylsydnoneimine
      (SIN-1, 100 microM), a molecule releasing nitric oxide and superoxide in solution
      at a pH of 7.0 or higher with tyrosine (10 microM). Using this method, 3-NT was
      detected in human liver microdialysate (levels up to 2.6 nM), although levels in
      rat spinal cord dialysate were below the limit of detection.

PMID- 16457773
TI  - [Abecedary of the "annales". Part 11].
AB  - The terms included and detailed in the present part are: confounding factor,
      false negative, false positive, reliability, forest plot, funnel plot.

PMID- 16457774
TI  - Design and engineering of photosynthetic light-harvesting and electron transfer
      using length, time, and energy scales.
AB  - Decades of research on the physical processes and chemical reaction-pathways in
      photosynthetic enzymes have resulted in an extensive database of kinetic
      information. Recently, this database has been augmented by a variety of high and
      medium resolution crystal structures of key photosynthetic enzymes that now
      include the two photosystems (PSI and PSII) of oxygenic photosynthetic organisms.
      Here, we examine the currently available structural and functional information
      from an engineer's point of view with the long-term goal of reproducing the key
      features of natural photosystems in de novo designed and custom-built molecular
      solar energy conversion devices. We find that the basic physics of the transfer
      processes, namely, the time constraints imposed by the rates of incoming photon
      flux and the various decay processes allow for a large degree of tolerance in the
      engineering parameters. Moreover, we find that the requirements to guarantee
      energy and electron transfer rates that yield high efficiency in natural
      photosystems are largely met by control of distance between chromophores and
      redox cofactors. Thus, for projected de novo designed constructions, the control
      of spatial organization of cofactor molecules within a dense array is initially
      given priority. Nevertheless, constructions accommodating dense arrays of
      different cofactors, some well within 1 nm from each other, still presents a
      significant challenge for protein design.

PMID- 16457775
TI  - Regulation of plant alternative oxidase activity: a tale of two cysteines.
AB  - Two Cys residues, Cys(I) and Cys(II), are present in most plant alternative
      oxidases (AOXs). Cys(I) inactivates AOX by forming a disulfide bond with the
      corresponding Cys(I) residue on the adjacent subunit of the AOX homodimer. When
      reduced, Cys(I) associates with alpha-keto acids, such as pyruvate, to activate
      AOX, an effect mimicked by charged amino acid substitutions at the Cys(I) site.
      Cys(II) may also be a site of AOX activity regulation, through interaction with
      the small alpha-keto acid, glyoxylate. Comparison of Arabidopsis AOX1a (AtAOX1a)
      mutants with single or double substitutions at Cys(I) and Cys(II) confirmed that
      glyoxylate interacted with either Cys, while the effect of pyruvate (or succinate
      for AtAOX1a substituted with Ala at Cys(I)) was limited to Cys(I). A variety of
      Cys(II) substitutions constitutively activated AtAOX1a, indicating that neither
      the catalytic site nor, unlike at Cys(I), charge repulsion is involved.
      Independent effects at each Cys were suggested by lack of Cys(II) substitution
      interference with pyruvate stimulation at Cys(I), and close to additive
      activation at the two sites. However, results obtained using diamide treatment to
      covalently link the AtAOX1a subunits by the disulfide bond indicated that Cys(I)
      must be in the reduced state for activation at Cys(II) to occur.

PMID- 16457776
TI  - Stronger renewal in human fear conditioning when tested with an acquisition
      retrieval cue than with an extinction retrieval cue.
AB  - It was previously demonstrated in our laboratory that conditioned fear in humans
      can renew after extinction, when this procedure took place in a different context
      (ABA-renewal [Vansteenwegen et al. (2005). Return of fear in a human differential
      conditioning paradigm caused by a return to the original acquisition context.
      Behaviour Research and Therapy, 43(3), 323-336]). Using the same experimental
      design, we now tested the power of retrieval cues to interact with this
      contextual renewal phenomenon. Two groups went through acquisition and extinction
      (in a different context). They were then tested in the original acquisition
      context and in the presence of a retrieval cue. In the acquisition-cue group,
      this cue previously featured during the acquisition procedure; in the extinction
      cue group, the cue previously featured during the extinction procedure. As
      expected, renewal of conditioned electro-dermal responding and retrospective
      expectancy ratings was strongest in the acquisition-cue group. Theoretical and
      clinical implications of this finding are discussed.

PMID- 16457777
TI  - Relations of the factors of the tripartite model of anxiety and depression to
      types of social anxiety.
AB  - Our primary goal was to examine the relations of the specific components of the
      tripartite model of anxiety and depression [Clark, L. A., Watson, D. (1991).
      Tripartite model of anxiety and depression: Psychometric evidence and taxonomic
      implications. Journal of Abnormal Psychology, 100, 316-336] to two types of
      social anxiety (social interaction anxiety and performance anxiety) in 148
      individuals with social phobia. In line with previous research, overall social
      anxiety was more closely related to the anhedonic depression (AD) or low positive
      affect factor of the tripartite model than to the physiological hyerarousal
      factor, controlling for general distress. However, as hypothesized, performance
      anxiety was more closely associated with the physiological hyerarousal factor,
      whereas social interaction anxiety was more closely associated with the AD or low
      positive affect factor. We also examined the convergent and discriminant validity
      of the Mood and Anxiety Symptom Questionnaire (MASQ; [Watson, D., Clark, L. A.
      (1991). The mood and anxiety symptom questionnaire. Unpublished manuscript,
      University of Iowa City]). Intercorrelations of the MASQ subscales were as
      expected, but correlations with measures of social anxiety, nonsocial anxiety,
      and depression provided only modest support for convergent and discriminant
      validity. Findings from this study provide a more detailed account of the
      specific components of the tripartite model that characterize the diversity of
      symptoms subsumed by social phobia.

PMID- 16457778
TI  - Negative cognitions and avoidance in emotional problems after bereavement: a
      prospective study.
AB  - Cognitive behavioural conceptualisations of grief propose that negative
      cognitions and avoidance strategies play a key role in emotional problems after
      bereavement. In the current study, this assumption was examined. Ninety-seven
      individuals who had lost a relative less than 5 months ago completed
      questionnaires tapping background and loss-related variables, negative cognitions
      (about the self, life, the future, and one's own grief reactions), avoidance, and
      symptoms of complicated grief (CG) and depression. Of these mourners, 70 people
      (72%) completed symptom measures again 6 months later at T2 (7-10 months after
      the loss), and 60 (62%) completed symptoms measures still 9 months later at T3
      (16-19 months after the loss). Among other things, results showed that all four
      cognitive variables and the avoidance variable were strongly associated with
      concurrent and prospective symptom levels, even when the influence of relevant
      background/loss-related variables was controlled. In addition, independent of
      initial symptom levels, most of the cognitive variables predicted later CG and
      depression. The avoidance variable only predicted additional variance in
      depression at T3 beyond T1 symptom levels. Findings indicate that negative
      cognitions are important in emotional problems after bereavement and that the
      role of avoidance in the development of these problems needs further scrutiny.

PMID- 16457779
TI  - Self-efficacy and social behavior.
AB  - Data regarding the relationship between self-efficacy and social behavior are
      limited, and questions remain about how to interpret the relationship of self
      efficacy to phobic behavior in general. The current study includes data regarding
      the relationship between self-efficacy ratings and social behavior. The data also
      allow tests of an alternative hypothesis that self-efficacy ratings represent a
      general prediction regarding the likely outcome regarding a task. If this
      hypothesis is correct, the relationship of self-efficacy to behavior should be
      moderated by task familiarity. The study involved 124 socially anxious
      participants who gave at least partial data on a variety of measures, including
      three speaking tasks. In accordance with the alternative hypothesis, self
      efficacy ratings best predicted behavior in reference to a familiar speaking
      task. Overall, self-efficacy showed only a moderate tendency to predict behavior.

PMID- 16457780
TI  - Pharmacological characterisation of the plant sesquiterpenes polygodial and
      drimanial as vanilloid receptor agonists.
AB  - This study was designed to assess the participation of transient receptor
      potential vanilloid 1 (TRPV1) in the biological effects induced by the plant
      derived sesquiterpenes polygodial and drimanial. In rat isolated urinary bladder,
      polygodial and drimanial produced a tachykinin-mediated contraction that was
      inhibited by combination of NK(1) and NK(2) tachykinin receptor antagonists, SR
      140333 and SR 48968. Furthermore, two different TRPV1 antagonists, capsazepine
      and ruthenium red prevented the contraction induced by both compounds. In
      addition, capsaicin, polygodial and drimanial displaced in a concentration
      dependent manner the specific binding sites of [(3)H]-resiniferatoxin to rat
      spinal cord membranes, with a IC(50) values of 0.48, 4.2 and 3.2 microM,
      respectively. Likewise, capsaicin, polygodial and drimanial promoted an increase
      of [(45)Ca(2+)] uptake in rat spinal cord synaptosomes. In cultured rat
      trigeminal neurons, polygodial, drimanial and capsaicin were also able to
      significantly increase the intracellular Ca(2+) levels, effect that was
      significantly prevented by capsazepine. Together, the present results strongly
      suggest that the pharmacological actions of plant-derived sesquiterpenes
      polygodial and drimanial, seem to be partially mediated by activation of TRPV1.
      Additional investigations are needed to completely define the pharmacodynamic
      properties of these sesquiterpenes.

PMID- 16457781
TI  - Rengyolone inhibits inducible nitric oxide synthase expression and nitric oxide
      production by down-regulation of NF-kappaB and p38 MAP kinase activity in LPS
      stimulated RAW 264.7 cells.
AB  - Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory
      responses. Rengyolone, a cyclohexylethanoid isolated from the fruits of Forsythia
      koreana, exhibits anti-inflammatory activity with unknown mechanism. In this
      study, we found that rengyolone has a strong inhibitory effect on the production
      of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Rengyolone also
      inhibited inducible nitric oxide synthase (iNOS) gene expression and
      cyclooxygenase 2 (COX-2) by lipopolysaccharide (LPS). In order to explore the
      mechanism responsible for the inhibition of iNOS gene expression by rengyolone,
      we investigated its effect on LPS-induced nuclear factor-kappaB (NF-kappaB)
      activation. The LPS-induced DNA binding activity of NF-kappaB was significantly
      inhibited by rengyolone, and this effect was mediated through inhibition of the
      degradation of inhibitory factor-kappaBalpha and phosphorylation of p38 MAP
      kinase. Furthermore, rengyolone suppressed the expression of ICE protein in IL
      1beta-treated D10S cells. Taken together, these results suggest that rengyolone
      attenuates the inflammation through inhibition of NO production and iNOS
      expression by blockade of NF-kappaB and p38 MAPK activation in LPS-stimulated RAW
      264.7 cells.

PMID- 16457782
TI  - The role of CREB in depression and antidepressant treatment.
AB  - Major depressive disorder is a severe clinical problem across the globe, with a
      lifetime risk of 10%-30% for women and 7%-15% for men. The World Health
      Organization ranks major depression at the top of the list in terms of disease
      burden, and this burden is expected to rise in the next decade as the prevalence
      of the disorder grows. Since the late 1950s, a wide range of antidepressant
      medications targeting the monoamine systems has been available to alleviate the
      symptoms of major depressive disorder. Although widely prescribed, such
      antidepressant medications are accompanied by a delay in effectiveness, as well
      as varied side effects. Therefore, further characterization of the biological
      mechanisms behind their function is crucial for the development of new and more
      effective treatments. One protein that could serve as a convergence point for
      multiple classes of antidepressant drugs is the transcription factor CREB (cyclic
      adenosine monophosphate response element binding protein). CREB is upregulated by
      chronic antidepressant treatment, and increasing CREB levels in rodent models
      results in antidepressant-like behaviors. Furthermore, postmortem studies
      indicate that CREB levels are increased in subjects taking antidepressants at the
      time of death. However, not all antidepressants increase CREB levels and/or
      activity, and reducing CREB levels in some brain regions also results in
      antidepressant-like behaviors. This review attempts to consolidate the
      information relevant to the structure and function of the CREB protein and
      describe how this relates to the mechanism of antidepressant drugs. Animal models
      in which CREB function is enhanced, by overexpression of the protein, or reduced,
      by expression of mutant forms of the protein or through gene deletion
      experiments, are summarized in terms of identifying a role for CREB in behavioral
      responses in depression tests that were originally designed to evaluate
      antidepressant efficacy. Human postmortem and genetic studies that implicate CREB
      in depression and antidepressant efficacy are also discussed.

PMID- 16457784
TI  - Stress during gestation alters postpartum maternal care and the development of
      the offspring in a rodent model.
AB  - BACKGROUND: Epidemiological studies suggest that environmental adversity can
      alter parental care and thus influence child development. We addressed the
      question of whether stressors can directly affect parental behavior using a
      rodent model of stable, individual differences in maternal behavior. METHODS:
      Lactating rat mothers were characterized as high or low in pup-directed
      licking/grooming (LG) behavior, rebred, and subjected to 7 days of intermittent
      stress or control conditions during gestation. Female rats were mated a third
      time without any subsequent intervention. Maternal behavior, oxytocin receptor
      (OTR) binding, and offspring behavior were examined. RESULTS: Stress reduced OTR
      levels and pup LG of high LG mothers to levels comparable with those of low LG
      mothers. The adult offspring of the gestational stress/high LG mothers resembled
      those of low LG mothers on behavioral measures of anxiety and maternal behavior,
      as well as OTR levels. The results of the third mating revealed an enduring
      effect of gestational stress on both mother and offspring maternal LG.
      CONCLUSIONS: These findings suggest that stress can directly alter maternal care
      through the neuroendocrine systems that normally regulate this behavior. Thus,
      the effects of environmental adversity can be transmitted across generations
      through a nongenomic mechanism involving maternal care.

PMID- 16457783
TI  - Cellular plasticity cascades: genes-to-behavior pathways in animal models of
      bipolar disorder.
AB  - BACKGROUND: Despite extensive research, the molecular/cellular underpinnings of
      bipolar disorder (BD) remain to be fully elucidated. Recent data has demonstrated
      that mood stabilizers exert major effects on signaling that regulate cellular
      plasticity; however, a direct extrapolation to mechanisms of disease demands
      proof that manipulation of candidate genes, proteins, or pathways result in
      relevant behavioral changes. METHODS: We critique and evaluate the behavioral
      changes induced by manipulation of cellular plasticity cascades implicated in BD.
      RESULTS: Not surprisingly, the behavioral data suggest that several important
      signaling molecules might play important roles in mediating facets of the complex
      symptomatology of BD. Notably, the protein kinase C and extracellular signal
      regulated kinase cascades might play important roles in the antimanic effects of
      mood stabilizers, whereas glycogen synthase kinase (GSK)-3 might mediate facets
      of lithium's antimanic/antidepressant actions. Glucocorticoid receptor (GR)
      modulation also seems to be capable to inducing affective-like changes observed
      in mood disorders. And Bcl-2, amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      receptors, and inositol homeostasis represent important pharmacological targets
      for mood stabilizers, but additional behavioral research is needed to more fully
      delineate their behavioral effects. CONCLUSIONS: Behavioral data support the
      notion that regulation of cellular plasticity is involved in affective-like
      behavioral changes observed in BD. These findings are leading to the development
      of novel therapeutics for this devastating illness.

PMID- 16457785
TI  - Early chronic blockade of NR2B subunits and transient activation of NMDA
      receptors modulate LTP in mouse auditory cortex.
AB  - In the auditory cortex, the properties of NMDA receptors depend primarily on the
      ratio of NR2A and NR2B subunits. NR2B subunit expression is high at the beginning
      of critical period and lower in adulthood. Because NMDA receptors are crucial in
      triggering long-term potentiation (LTP) and long-term depression, developmental
      or experience-dependent modification of NMDAR subunit composition is likely to
      influence synaptic plasticity. To examine how NMDA subunit change during
      postnatal development affect the adult synaptic plasticity, we employed chronic
      ifenprodil blockade of NR2B subunits and analyzed evoked field potentials in
      adult C57BL/6 mice auditory cortex (AC). We found that chronic loss of NR2B
      activity led to a decline in LTP magnitude in the AC of adult mice. Adding NMDA
      to the artificial cerebrospinal fluid (ACSF) in blocked mice had the opposite
      effect, producing LTP magnitudes at or exceeding those found in treated or
      untreated animals. These results suggest that, even in adulthood when NR2B
      expression is downregulated, these receptor subunits play an important role in
      experience-dependent plasticity of mouse auditory cortex. Blockade from P60 did
      not result in any decrease of LTP amplitude, suggesting that chronic block in
      postnatal period may permanently affect cortical circuits so that they cannot
      produce significant LTP in adulthood.

PMID- 16457786
TI  - Task- and EEG-correlated analyses of BOLD MRI responses to eyes opening and
      closing.
AB  - Variations of a subject's vigilance may pose a severe confound during functional
      brain mapping. Here, we focused on BOLD MRI responses to eyes opening and closing
      in complete darkness and the associated changes in the EEG's alpha frequency band
      (Berger's effect) as a possible approach to this problem. In awake subjects, BOLD
      MRI activation patterns were positively correlated to eyes opening and negatively
      to alpha power. In contrast, activation patterns of subjects with diminished
      wakefulness as determined by alpha band analysis were negatively correlated to
      eyes opening. We conclude that a control of the subjects' state of wakefulness
      must be of prime concern for functional MRI, especially for paradigms which allow
      for a free shift of vigilance.

PMID- 16457787
TI  - Changes in corticomotor excitability of forearm muscles in relation to static
      shoulder positions.
AB  - We examined whether the recruitment properties of the corticospinal pathway to
      forearm muscles are influenced by variations of the shoulder joint angle. Flexor
      carpi radialis (FCR) and extensor carpi radialis (ECR) muscles motor evoked
      potentials (MEPs) in response to transcranial magnetic stimulation were examined
      during different static positions of shoulder joint in the horizontal plane: from
      30 degrees abduction to 30 degrees adduction. We found that at 30 degrees
      shoulder adduction, maximum slope and plateau phase of the ECR and FCR input
      output relationship (i.e., relation between MEP size and stimulus intensity) were
      significantly higher and lower than at 30 degrees abduction of the shoulder
      joint, respectively. Intracortical inhibition (ICI) and intracortical
      facilitation (ICF) of the FCR were assessed using a paired-magnetic pulse
      paradigm. A significant decrease in ICF was observed after changing shoulder
      position from 30 degrees abduction to 30 degrees adduction. On the contrary, no
      variation in the amount of ICI occurred in relation to the same changes in
      shoulder position. FCR H-reflex to electrical stimulation of median nerve at
      elbow did not differ significantly between the two shoulder positions. We
      conclude that shoulder position influences the recruitment efficiency (gain) of
      the corticospinal volleys to motoneurones of forearm muscles. It is proposed that
      activity of peripheral receptors signaling static shoulder position influences
      corticomotor excitability of forearm muscles mainly at cortical level, although
      C3-C4 propriospinal system could be also involved. It is proposed that the above
      changes in corticomotoneuronal excitability to forearm muscles as function of
      shoulder joint position are part of a global proximal-distal synergy operating
      throughout reaching movements.

PMID- 16457788
TI  - Lesion of the caudal ventrolateral medulla prevents the induction of hypertension
      by adenosine receptor blockade in rats.
AB  - The continuous infusion for 7 days of the adenosine receptor antagonist 1,3
      dipropyl-8-sulfophenylxanthine (DPSPX) causes a sustained hypertension in rats,
      with an enhancement of sympathetic neurotransmission and activation of the renin
      angiotensin system. We studied the involvement of the caudal ventrolateral
      medulla in the establishment of this hypertensive model by evaluating the effect
      of local lesioning in blood pressure (BP). Male adult Wistar rats received
      stereotaxic injections of 0.3 mul of saline or quinolinic acid (QA; 180 mM) in
      the caudal ventrolateral medulla followed by abdominal implant of minipump for
      infusion of saline or DPSPX (90 microg(-1) kg(-1) h(-1)). BP was measured in
      conscious animals every 2 days for 12 days. The sustained increase of BP (22.1 mm
      Hg; P < 0.001) detected in rats infused with DPSPX was reverted (6.7 mm Hg; P >
      0.05) from day six onwards in animals with lesion of the lateralmost part of
      caudal ventrolateral medulla (VLMlat). The present results suggest that the
      development of hypertension induced by adenosine receptor antagonist involves the
      participation of the VLMlat. They further add new data as to the functional
      complexity of this medullary area involved in a variety of functions such as
      cardiovascular, respiratory, motor and pain control.

PMID- 16457789
TI  - Aging associated changes in amygdalar corticotropin-releasing hormone (CRH) and
      CRH-binding protein in Fischer 344 rats.
AB  - Behavioral adaptation in aging may become impaired from abnormal expression of
      amygdalar corticotropin-releasing hormone (CRH) and/or CRH-binding protein (CRH
      BP). In this study, we serially sectioned the amygdala in 4-, 12-, and 24-month
      old Fischer 344 rats following perfusion with 4% paraformaldehyde. We determined
      the amount of CRH and CRH-BP containing cells as well as the density of fibers
      expressing CRH or CRH-BP utilizing densitometric methods. Images were digitized
      using Zeiss Axiovision software and densitometrically analyzed using Scion Image.
      Both sides were analyzed in sections cut at 30 mum thickness. Cell counts of CRH
      BP containing cells in the basolateral and lateral nucleus of the amygdala were
      lower in 24-month-old rats vs. 4-month-old rats, respectively (mean cells/section
      +/- SE): 31 +/- 6 vs. 72 +/- 10 (n = 3; P < 0.05 via ANOVA and Fisher's PLSD).
      There was a trend for cell counts of CRH containing cells in the central nucleus
      of the amygdala to be lower in 24-month-old rats vs. 4-month-old rats,
      respectively 28 +/- 7 vs. 47 +/- 9 (n = 3; P = 0.07 via ANOVA). Densitometric
      analysis of the number of CRH-BP positive fibers revealed no age differences in
      CeA; however, with regards to CRH-positive fibers, both 4- and 12-month rats had
      greater CeA CRH immunoreactivity relative to 24-month-old rats (Ps < 0.05 via
      ANOVA and Fisher's PLSD). These changes may contribute to impaired adaptations to
      stress, cognitive decline, and other pathophysiological processes during aging.

PMID- 16457790
TI  - Alcohol consumption alters dopamine transporter sites in Wistar-Kyoto rat brain.
AB  - Even though animal and human studies show alterations in dopamine transporter
      (DAT) sites after alcohol withdrawal, the role of DAT in influencing either
      alcoholic or depressive behavior has not been examined extensively. Given that
      the Wistar-Kyoto (WKY) rat is a putative animal model of depressive behavior, the
      present study examined the effects of chronic alcohol consumption on DAT sites in
      WKY versus Wistar (WIS) rats. Brains from both strains were sectioned for
      autoradiographic analysis of [3H]-GBR12935 binding to DAT sites after 24 days of
      alcohol exposure. The results indicated that WKY rats consumed a greater amount
      of alcohol (P < 0.001) than WIS rats did throughout the experiment.
      Autoradiographic analyses of discrete brain regions indicated that alcohol
      consumption increased DAT sites in a greater number of brain areas in WKY
      compared to WIS rats. In WKY rats, the binding of [3H]-GBR12935 to DAT sites was
      increased in the basolateral, central and lateral nuclei of the amygdala, lateral
      nucleus of the hypothalamus, olfactory tubercle, caudate-putamen, nucleus
      accumbens and substantia nigra (P < 0.05) and decreased in the ventromedial
      nucleus of the hypothalamus and the CA1 region of the hippocampus. In WIS rats,
      alcohol consumption increased DAT sites in the CA1 region of the hippocampus,
      basolateral nucleus of the amygdala, ventral tegmental area and substantia nigra,
      and decreased DAT sites in the lateral and ventromedial hypothalamus and dentate
      gyrus. These results indicate a strain dependent alteration in DAT sites which
      may be related to altered dopamine neurotransmission in select brain regions
      following alcohol consumption.

PMID- 16457791
TI  - Nonparticipation of nuclear factor kappa B (NFkappaB) in the signaling cascade of
      c-Jun N-terminal kinase (JNK)- and p38 mitogen-activated protein kinase (p38MAPK)
      dependent tumor necrosis factor alpha (TNFalpha) induction in lipopolysaccharide
      (LPS)-stimulated microglia.
AB  - The molecular mechanism of cytotoxic cytokine tumor necrosis factor alpha
      (TNFalpha) induction in microglia remains to be clarified. We have previously
      reported that p38 mitogen-activated protein kinase (p38MAPK) is an important
      signaling molecule for the induction of TNFalpha in lipopolysaccharide (LPS)
      stimulated microglia. Recently, we have shown that c-Jun N-terminal kinase (JNK)
      is associated with the induction of TNFalpha. Furthermore, using an NFkappaB
      inhibitor (SN50), we discovered that activation of nuclear factor kappaB
      (NFkappaB) may also be linked to TNFalpha induction. We therefore examined the
      relationship between NFkappaB and the two MAPKs (p38MAPK and JNK) in the
      signaling cascade of TNFalpha induction in LPS-stimulated microglia. NFkappaB
      inhibitor SN50 decreased the induction of TNFalpha under the suppressed NFkappaB
      activation. However, SN50 was found to prevent the activation of MKK3/6-p38MAPK
      and MKK4-JNK pathways. On the other hand, the other NFkappaB inhibitor ammonium
      pyrrolidine dithiocarbamate (APDC) neither prevented the activation of p38MAPK
      and JNK nor inhibited TNFalpha induction in LPS-stimulated microglia, although it
      was confirmed to serve as an NFkappaB inhibitor. These results suggest that both
      MKK3/6-p38MAPK and MKK4-JNK pathways are important signaling cascades leading to
      the induction of TNFalpha in LPS-stimulated microglia, but that NFkappaB itself
      is not required for this induction.

PMID- 16457792
TI  - Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture)
      on inflammatory pain in the rat model of collagen-induced arthritis: Mediation by
      alpha2-Adrenoceptors.
AB  - The antinociceptive effect and the mechanism of bee venom acupuncture (BVA) on
      inflammatory pain, especially in the rat model of collagen-induced arthritis
      (CIA), have not yet been fully studied. This study was designed to investigate
      the antinociceptive effect and its mu-opioid and alpha2-adrenergic mechanism of
      BVA in the CIA rat model. To induce CIA, male Sprague-Dawley rats were immunized
      with bovine type II collagen emulsified in Freund's incomplete adjuvant followed
      by a booster injection 14 days later. The antinociceptive effect was evaluated by
      tail flick latency (TFL). After induction of arthritis, the inflammatory pain
      threshold decreased as time passed, and there was no big change of the pain
      threshold after 3 weeks. Three weeks after the first immunization, BVA (0.25
      mg/kg) injected into the Zusanli acupoint (ST36) showed the antinociceptive
      effect. Furthermore, the antinociceptive effect of BVA was blocked by yohimbine
      (alpha2-adrenergic receptor antagonist, 2 mg/kg, i.p) pretreatment, but not by
      naloxone (mu-opioid receptor antagonist, 2 mg/kg, i.p.) pretreatment. These
      results suggest that BVA can relieve inflammatory pain in CIA and the
      antinociceptive effect of BVA can be mediated by alpha2-adrenergic receptor.

PMID- 16457793
TI  - Differential expression of alpha-E-catenin and alpha-N-catenin in the developing
      cerebral cortex.
AB  - Alpha (alpha) catenin proteins can regulate both cell adhesion and cell
      proliferation. Here, we characterize the expression of two forms of alpha
      catenin, alphaE-catenin and alphaN-catenin, in the developing cerebral cortex and
      primary cortical cultures. In situ hybridization and immunofluorescence studies
      reveal that alphaE-catenin is highly expressed in neuroepithelial precursor cells
      in the developing cortical ventricular zone, with markedly reduced expression in
      the cortical plate; in contrast, alphaN-catenin expression is low in the
      ventricular zone and high in the developing cortical plate. In the ventricular
      zone, immunoreactivity for both alphaE-catenin and alphaN-catenin is enriched in
      rings at the lumenal surface, reflecting localization at adherens junctions
      together with beta-catenin. Expression of alphaE-catenin in primary cortical
      precursor cultures is initially robust, but declines as neural precursors
      differentiate into neurons. Reflecting its expression pattern in vivo, alphaN
      catenin is expressed in both neural precursors as well in neurons differentiated
      in culture. These differential expression patterns of alphaE-catenin and alphaN
      catenin suggest both distinct and overlapping functions during cortical
      development.

PMID- 16457794
TI  - Dual adaptation to sensory conflicts during whole-body rotations.
AB  - A dual adaptation paradigm was used in order to study the adaptation to two
      conditions of conflicting visual and kinesthetic and vestibular information.
      Adaptation was induced in humans by modifying visual information during whole
      body rotations with the help of a virtual reality set-up. Real rotations'
      amplitudes were factored by a gain of 0.5 or 1.5. The two conditions were
      associated to a visual context cue. The aim of the experiment was to provide
      support for either the feedback or the feedforward model of adaptive states
      switch. Results show that subjects could adapt to the two conditions of conflict
      during whole-body rotations. However, the two conflict situations have been found
      to differ both in their motor dynamics and in their susceptibility to adaptation,
      as it seems that the adaptation is more complete in the condition of gain 1.5,
      i.e., faster and more precise. Subjects could be divided into two groups
      according to their ability to use contextual information to switch between
      adaptive gains. The visual cues were sufficient for some subjects to switch
      adaptive state, which corresponds to a context-dependent dual adaptation, or
      feedforward model of switching. Other subjects showed a switch cost maintained
      across the experiment, corresponding with a stimulus-dependent adaptation, or
      feedback model of switching. We are suggesting that the process enabling
      switching between adaptive states depends on subjects' abilities to use
      contextual cues of certain types, and thus on their "perceptive styles". This
      could explain the variability of results obtained in the literature.

PMID- 16457795
TI  - Implicit action encoding influences personal-trait judgments.
AB  - When an observed action (e.g., kicking) is compatible to a to be produced action
      (e.g., a foot-key response as compared to a finger-key response), then the self
      produced action is more fluent, that is, it is more accurate and faster. A series
      of experiments explore the notion that vision-action compatibility effects can
      influence personal-trait judgments. It is demonstrated that when an observed
      individual carries out an action that is compatible with the participants'
      response, (1) this individual is identified more fluently, and (2) the observed
      individual's personality is attributed with the properties of the observed
      action. For example, if it is easier to identify one individual with a foot
      response when he is seen kicking a ball, as compared to typing, he is perceived
      to be more 'sporty'. In contrast, if it is easier to identify one individual with
      a finger response when he is seen typing as compared to kicking a ball, he is
      associated with the 'academic' trait. These personal-trait judgment effects can
      be observed with explicit measures, where participants are asked to rate the
      sporty/academic nature of the person on a scale. They are also obtained when
      implicit measures are taken in a priming task, where participants are never
      explicitly asked to rate the personalities of the individuals. A control
      experiment rules out that these personal-trait effects are merely due to an
      association of motor responses (foot, finger) to individuals while identifying
      them, but that these effects depend on a prior manipulation of vision-action
      fluency.

PMID- 16457796
TI  - Separate pathways of RNA recruitment lead to the compartmentalization of the
      zebrafish germ plasm.
AB  - The maternal RNAs vasa, dead end, nanos1, and daz-like all become localized to
      the peripheral ends of the first and second cleavage furrows, where they form
      part of the zebrafish germ plasm. We show that aggregates of a first class of
      germ plasm components, which include dead end, nanos1, and vasa RNAs, are
      initially present in a wide cortical band at the animal pole. Aggregates
      containing these three RNAs appear to be associated with f-actin, which during
      the first cell cycle undergoes a microtubule-dependent movement towards the
      periphery as well as circumferential alignment. These cytoskeletal rearrangements
      lead to the further aggregation of particles containing these RNAs and their
      concomitant recruitment to the forming furrow. Aggregates containing a second
      class of germ plasm RNA components, which include the transcript for daz-like,
      translocate along the plane of the cortex towards the animal pole, where they are
      recruited to the germ plasm. After recruitment to the furrow, these two classes
      of RNAs occupy overlapping yet distinct regions of the germ plasm, and this
      arrangement is maintained during the early cleavage stages. Our observations
      suggest that separate pathways of RNA recruitment facilitate the
      compartmentalization of the zebrafish germ plasm.

PMID- 16457798
TI  - Dual origin of avian lymphatics.
AB  - The earliest signs of the lymphatic vascular system are the lymph sacs, which
      develop adjacent to specific embryonic veins. It has been suggested that sprouts
      from the lymph sacs form the complete lymphatic vascular system. We have studied
      the origin of the jugular lymph sacs (JLS), the dermal lymphatics and the lymph
      hearts of avian embryos. In day 6.5 embryos, the JLS is an endothelial-lined
      sinusoidal structure. The lymphatic endothelial cells (LECs) stain (in the quail)
      positive for QH1 antibody and soybean agglutinin. As early as day 4, the anlagen
      of the JLS can be recognized by their Prox1 expression. Prox1 is found in the
      jugular section of the cardinal veins, and in scattered cells located in the
      dermatomes along the cranio-caudal axis and in the splanchnopleura. In the quail,
      such cells are positive for Prox1 and QH1. In the jugular region, the veins co
      express the angiopoietin receptor Tie2. Quail-chick-chimera studies show that the
      peripheral parts of the JLS form by integration of cells from the paraxial
      mesoderm. Intra-venous application of DiI-conjugated acetylated low-density
      lipoprotein into day 4 embryos suggests a venous origin of the deep parts of the
      JLS. Superficial lymphatics are directly derived from the dermatomes, as shown by
      dermatome grafting. The lymph hearts in the lumbo-sacral region develop from a
      plexus of Prox1-positive lymphatic capillaries. Both LECs and muscle cells of the
      lymph hearts are of somitic origin. In sum, avian lymphatics are of dual origin.
      The deep parts of the lymph sacs are derived from adjacent veins, the superficial
      parts of the JLS and the dermal lymphatics from local lymphangioblasts.

PMID- 16457797
TI  - Mxi1 is essential for neurogenesis in Xenopus and acts by bridging the pan-neural
      and proneural genes.
AB  - We have isolated and characterized Xenopus Mxi1, a member of the Myc/Max/Mad
      family of bHLHZip transcription factors. Xmxi1 transcripts are present during
      gastrulation and early neurula stages, earlier and in broader domains as compared
      to the neuronal determination factor neurogenin (X-ngnr-1). Consistent with an
      early role in neurogenesis, Xmxi1 is positively regulated by Sox3, SoxD, and
      proneural genes, as well as negatively by the Notch pathway. Loss-of-function
      experiments demonstrate an essential role for Xmxi1 in the establishment of a
      mature neural state that can be activated by factors that induce neuronal
      differentiation, such as SoxD and X-ngnr-1. Overexpression of Xmxi1 in Xenopus
      embryos results in ectopic activation of Sox3, an early pan-neural marker of
      proliferating neural precursor cells. Within the neural plate, the neuronal
      differentiation marker N-tubulin and cell cycle control genes such as XPak3 and
      p27(Xic1) are inhibited, but the expression of early determination and
      differentiation markers, including X-ngnr-1 and X-MyT1, is not affected.
      Inhibition of neuronal differentiation by Xmxi1 is only transient, and, at early
      tailbud stages, both endogenous and ectopic neurogenesis are observed. While
      Xmxi1 enhances cell proliferation and apoptosis in the early Xenopus embryo, both
      activities appear not to be required for the function of Xmxi1 in primary
      neurogenesis.

PMID- 16457799
TI  - Rab11-FIP4 is predominantly expressed in neural tissues and involved in
      proliferation as well as in differentiation during zebrafish retinal development.
AB  - Rab11 family interacting protein 4 (Rab11-FIP4) was initially identified in
      humans as an Rab11-binding protein, but its biological function has remained
      unknown. We cloned the zebrafish orthologue of Rab11-FIP4 (zRab11-FIP4) and
      analyzed its function in vivo by using antisense morpholino. zRab11-FIP4 was
      expressed as 2 alternative transcripts, i.e., the longer A-form predominantly
      expressed in neural tissues and the shorter B-form expressed ubiquitously; and in
      situ hybridization revealed that the A-form was the dominant form. In the
      developing retina, zRab11-FIP4 was expressed in progenitors throughout the retina
      at early stages; and then, along with the differentiation, the expression became
      gradually restricted to the ganglion cell layer and ciliary marginal zone. zRab11
      FIP4A knockdown embryos exhibited eye phenotypes similar to those of the shh
      mutant, such as a small eye with impaired cell proliferation and the delay in
      cell-cycle exit and differentiation of retinal progenitors. The lack of induction
      of p57kip2 and enhanced expression of cyclin D1 were observed in the morphant
      retina. Importantly, the delay in cell-cycle exit was rescued by ectopic
      expression of either p57Kip2 or dominant-negative PKA, suggesting that Rab11
      FIP4A plays pivotal roles in retinal development by regulating Shh signaling and
      a mechanism acting in parallel with Shh signaling in the control of cell-cycle
      exit.

PMID- 16457800
TI  - The caudal-related homeobox genes cdx1a and cdx4 act redundantly to regulate hox
      gene expression and the formation of putative hematopoietic stem cells during
      zebrafish embryogenesis.
AB  - The hox genes play a central role in organogenesis and are implicated in the
      formation of hematopoietic stem cells (HSCs). The cdx genes encode homeodomain
      transcription factors that act as master regulators of the hox genes. In
      zebrafish, mutations in cdx4 cause a severe, but not complete, deficit in
      embryonic blood cells. Here, we report the expression and function of cdx1a, a
      zebrafish Cdx1 paralogue. Using morpholino-mediated knockdown of cdx1a in a cdx4
      mutant background, we show that a deficiency in both cdx genes causes a severe
      perturbation of hox gene expression and a complete failure to specify blood. The
      hematopoietic defect in cdx-deficient embryos does not result from a general
      block in posterior mesoderm differentiation as endothelial cells and kidney
      progenitors are still formed in the doubly deficient embryos. In addition, cdx
      deficient embryos display a significant reduction in runx1a(+) putative HSCs in
      the zebrafish equivalent to the aorta-gonad-mesonephros (AGM) region.
      Overexpressing hoxa9a in cdx-deficient embryos rescues embryonic erythropoiesis
      in the posterior mesoderm as well as the formation of HSCs in the AGM region.
      Taken together, these results suggest that the cdx-hox pathway plays an essential
      role in the formation of both embryonic erythroid cells and definitive HSCs
      during vertebrate embryogenesis.

PMID- 16457801
TI  - ARI-1, an RBR family ubiquitin-ligase, functions with UBC-18 to regulate
      pharyngeal development in C. elegans.
AB  - The LIN-35 retinoblastoma protein homolog and the ubiquitin-conjugating enzyme
      UBC-18 function redundantly to control an early step of pharyngeal morphogenesis
      in C. elegans. In order to identify ubiquitin-ligases acting downstream of UBC
      18, we carried out a two-hybrid screen using UBC-18 as the bait molecule. Our
      screen identified three putative ubiquitin-ligases, one of which, ARI-1, showed
      genetic interactions leading to defective pharyngeal development that were
      identical to that previously observed for UBC-18. ARI-1 is a member of the RBR
      family of ubiquitin-ligases and contains a C-terminal motif that places it within
      the highly conserved Ariadne subfamily of RBR ligases. Our analyses indicate that
      ARI-1 is the principal Ariadne family member in C. elegans that is involved in
      the control of pharyngeal development with UBC-18. Using GFP reporters, we find
      that ARI-1 is expressed dynamically in a wide range of tissues including muscles
      and neurons during embryonic and postembryonic development. We also provide
      evidence that dsRNA species containing 14 or fewer base pairs of contiguous
      identity with closely related mRNAs are sufficient to mediate off-target
      silencing in C. elegans.

PMID- 16457802
TI  - Risk assessment of exposure to indoor aerosols associated with Chinese cooking.
AB  - Cooking is an important source of indoor aerosols in residential homes and
      buildings with non-smokers, and thus has public health implications. However,
      limited information is currently available in the published literature on the
      physical and chemical characteristics of aerosols produced by gas cooking.
      Consequently, a comprehensive study was carried out to investigate the physical
      (number and mass concentrations and size distributions) and chemical (metals)
      properties in a typical Chinese food stall in Singapore where stir-frying in a
      wok is the most common cooking method using gas stove. To assess the contribution
      of cooking activities to indoor particle concentrations, aerosol measurements
      were performed in two distinct time periods, i.e., during cooking and non-cooking
      hours. The average mass concentrations of fine particles (PM(2.5)) and metals
      increased by a factor of 12 and 11, respectively, from 26.7 and 1.5microgm(-3)
      during non-cooking hours to 312.4 and 15.6microgm(-3) during cooking hours. The
      average number concentration was also elevated by a factor of 85, from
      9.1x10(3)cm(-3) during non-cooking hours to 7.7x10(5)cm(-3) during cooking hours.
      Real-time particle measurements showed that about 80% of the particles associated
      with cooking are ultrafine particles in terms of particle counts. To evaluate the
      potential health threat due to inhalation of air pollutants released from gas
      cooking, the health risk estimates based on exposure and dose-response
      assessments of metals were calculated for a maximally exposed individual. The
      findings indicate that the indoor air quality existing at the food stall may pose
      adverse health effects over long-term exposure to cooking emissions.

PMID- 16457803
TI  - Proximity to pulp and paper mills and wheezing symptoms among adolescents in
      North Carolina.
AB  - Using data from the North Carolina School Asthma Survey about the respiratory
      health of 64,432 adolescents attending public schools in North Carolina and data
      provided by school employees about the environmental health conditions of the
      school buildings, we assessed the prevalence of daytime wheezing during the past
      year among students estimated to be exposed to air pollutants arising from pulp
      and paper mills located near the schools. Of the schools the students attended,
      14% (37/266) were located within 30 miles of one or more pulp and paper mills and
      odor from the mills was identified by survey respondents for 9 of the 266
      schools. The prevalences of daytime wheezing in smokers and nonsmokers with
      household cigarette smoke exposure were elevated among students attending schools
      located within 30 miles of a pulp and paper mill, compared to the prevalence
      among students attending schools located beyond 30 miles (10 miles, prevalence
      ratio (PR): 1.21, 95% confidence interval (95% CI): 0.99, 1.43; 10-30 miles, PR:
      1.06, 95% CI: 0.96, 1.16) and among students attending schools with noticeable
      odor from a pulp and paper mill (PR: 1.12, 95% CI: 0.93, 1.31). These results
      indicate a possible association between paper mill location and wheezing symptoms
      among adolescents and suggest that community-based exposure to pulp and paper
      mill emissions may have a greater impact on smokers and individuals exposed to
      cigarette smoke in the home than on nonsmokers without such household exposure.

PMID- 16457804
TI  - Ethnic differences in ecological concerns: Spanish-speaking Hispanics are more
      concerned than others.
AB  - We postulated that environmental concern encompasses a wide range of different
      issues, often lumping pollution with habitat loss (or land use) and ecological
      resources (fish and wildlife). In this paper, we compare perceptions about a
      range of environmental and ecological resource issues, and explore ethnic/racial
      differences. We surveyed 1513 residents of New Jersey about "environmental
      concerns", using both general environmental questions (two questions: How serious
      are environmental problems in New Jersey? Are you concerned about the loss of
      open space?) and ecological resource questions (12 questions: e.g., how important
      is planting trees in your neighborhood, how concerned are you about loss of
      breeding and feeding habitat for fish and birds?) in New Jersey. Not all concerns
      were rated equally. For the ecological questions, there were no ethnic
      differences in concerns over preserving areas around water supplies, loss of
      places to hunt and fish, and loss of places for quiet walks and cycling, but
      there were for the other 9 ecological concerns. For eight of these nine concerns,
      Spanish-speaking Hispanics were more concerned than others (including English
      speaking Hispanics). We divided the ecological resources into three categories:
      ecological services (clean water and safety), ecological resources (fish and
      wildlife), and recreational services. The strongest correlates of people's
      association with enlarging and enhancing recreational services were Spanish
      speaking Hispanics, who are supportive of regulations and believe local
      government is not doing enough for environmental problems. People concerned about
      the loss of ecological resources and open space believe the federal government
      and the state are not doing enough for the environment, were non-Hispanic White,
      want continued environmental regulations, were longer-term residents, were high
      school graduates, and were older (45-54 years). People interested in ecological
      services were college-educated, non-White, not rich, females that did not trust
      DEP's environmental actions, and thought the state was not doing enough
      environmentally. There was a high correlation between general environmental
      concern and the ecological resource variables for the population overall, and for
      each ethnic group. Overall, only 39% of the subjects were very concerned about
      the seriousness of environmental problems in New Jersey, yet from 36% to 81% of
      the people were very concerned about 11 of 12 ecological issues. This indicates
      that people respond different to the term "environmental problems" compared to
      specific "ecological resource" issues. The greatest concern (81%) was for
      preserving areas around water supplies and cleaning up garbage in the parks, and
      the least concern was for the loss of places to hunt and fish (26%). Our results
      indicate that people distinguish between general environmental concern and
      ecological concerns, as well as distinguishing ecological services from
      ecological resources.

PMID- 16457805
TI  - Agents against cytokine synthesis or receptors.
AB  - Various cytokines play a critical role in pathophysiology of chronic inflammatory
      lung diseases including asthma and chronic obstructive pulmonary disease (COPD).
      The increasing evidence of the involvement of these cytokines in the development
      of airway inflammation raises the possibility that these cytokines may become the
      novel promising therapeutic targets. Studies concerning the inhibition of
      interleukin (IL)-4 have been discontinued despite promising early results in
      asthma. Although blocking antibody against IL-5 markedly reduces the infiltration
      of eosinophils in peripheral blood and airway, it does not seem to be effective
      in symptomatic asthma, while blocking IL-13 might be more effective. On the
      contrary, anti-inflammatory cytokines themselves such as IL-10, IL-12, IL-18, IL
      23 and interferon-gamma may have a therapeutic potential. Inhibition of TNF-alpha
      may also be useful in severe asthma or COPD. Many chemokines are also involved in
      the inflammatory response of asthma and COPD through the recruitment of
      inflammatory cells. Several small molecule inhibitors of chemokine receptors are
      now in development for the treatment of asthma and COPD. Antibodies that block IL
      8 reduce neutrophilic inflammation. Chemokine CC3 receptor antagonists, which
      block eosinophil chemotaxis, are now in clinical development for asthma therapy.
      As many cytokines are involved in the pathophysiology of inflammatory lung
      diseases, inhibitory agents of the synthesis of multiple cytokines may be more
      useful tools. Several such agents are now in clinical development.

PMID- 16457806
TI  - (-)-Epigallocatechin gallate attenuates acute stress responses through GABAergic
      system in the brain.
AB  - (-)-Epigallocatechin gallate (EGCG), a flavonoid, is the principal catechin found
      in green tea and is distributed in the brain after tea consumption. The aim of
      the present study was to investigate the effects of EGCG in the chick brain under
      an acute stressful condition and to clarify the mechanism by which EGCG
      attenuates stress behavior with special reference to gamma-aminobutyric acid
      (GABA). Intracerebroventricular (i.c.v.) injection of EGCG (50, 100 and 200
      microg) suppressed the vocalization which normally occurs during social
      separation stress. EGCG decreased the time spent in active wakefulness and
      induced sleep-like behavior in a dose-dependent manner. Additionally, i.c.v.
      injection of EGCG attenuated plasma corticosterone release under social
      separation stress. These effects of EGCG on distress-induced vocalization were
      significantly attenuated by the GABAA receptor antagonist picrotoxin but not by
      the GABAB receptor antagonist CGP 54626 (3-N-(1-(3,4-dichlorophenyl)ethylamino)-2
      hydroxypropyl cyclohexylmethyl phosphinic acid hydrochloride). These results
      indicate that EGCG has sedative and hypnotic effects in the brain, partially
      through GABAA receptors, and consequently moderates an acute stress response.

PMID- 16457807
TI  - Corticosteroids and adrenoceptor agonists: the compliments for combination
      therapy in chronic airways diseases.
AB  - The combination of inhaled corticosteroids and long-acting beta2-adrenoceptor
      agonists is increasingly used as maintenance therapy in patients with moderate to
      severe asthma or chronic obstructive pulmonary disease (COPD). The main effect of
      inhaled corticosteroids is thought to be mediated through suppression of airway
      inflammation, while long-acting beta2-adrenoceptor agonists are thought to work
      by inducing bronchodilation. However, there is emerging data to indicate that
      these two classes of drugs interact positively with each other, leading to added
      or perhaps synergistic benefits for patients. Corticosteroids enhance the
      expression of beta2-adrenoceptor, thus providing protection against
      desensitization and development of tolerance to beta2-adrenoceptor agonists,
      which may occur with prolonged use of these medications. Long-acting beta2
      adrenoceptor agonists, on the other hand, may amplify the anti-inflammatory
      effects of corticosteroids by accelerating nuclear translocation of the
      glucocorticoid receptor complex, and enhancing transcription and expression of
      steroid-inducible genes in pro-inflammatory cells. In clinical trials,
      corticosteroids in combination with long-acting beta2-adrenoceptor agonists
      reduce exacerbation rates, and improve lung function and health status of
      patients with moderate to severe asthma or COPD beyond that achieved by
      individual component therapy. Their effects on mortality are unknown. There is a
      large clinical trial currently underway, which will provide mortality data by the
      year 2006. On balance, clinical evidence supports the use of combination therapy
      in moderate to severe asthma and COPD.

PMID- 16457808
TI  - The broken balance in aspirin hypersensitivity.
AB  - Aspirin was introduced into medicine over a century ago and has become the most
      popular drug in the world. Although the first hypersensitivity reaction was
      described soon after aspirin had been marketed, only recently a phenomenon of
      cysteinyl leukotriene overproduction brought new insights on a balance between
      pro- and anti-inflammatory mediators derived from arachidonic acid. We describe
      the most common clinical presentations of aspirin hypersensitivity, i.e. aspirin
      induced asthma, rhinosinusitis and aspirin-induced urticaria. We also present
      their biochemical background. Despite relatively high incidence of these
      reactions, aspirin hypersensitivity remains underdiagnosed worldwide. Acute
      reactions of aspirin hypersensitivity are elicited via cyclooxygenase inhibition
      by non-steroid anti-inflammatory drugs. Coxibs, selective inhibitors of
      cyclooxygenase-2 isoenzyme, do not precipitate symptoms in susceptible patients.
      Though hypersensitivity correlates with cyclooxygenase-1 inhibition, diminished
      tissue expression was described only for cyclooxygenase-2. Aspirin-induced asthma
      and aspirin-induced urticaria, in a substantial part of the patients, are driven
      by a release of mediators from activated mast cells. These cells in physiological
      conditions are under inhibitory control of prostaglandin E2. The origin of
      aspirin hypersensitivity remains unknown, but accumulating data from genetic
      studies strongly suggest that environmental factor, possibly a common viral
      infection, can trigger the disease in susceptible subjects.

PMID- 16457809
TI  - Mechanisms of antiplatelet activity of PC-09, a newly synthesized pyridazinone
      derivative.
AB  - In this study, we examined whether PC-09, a new pyridazinone derivative, has
      antiplatelet activity in vitro and further investigated the possible mechanisms
      involved. Pretreatment with PC-09 resulted in an inhibition on rabbit platelet
      aggregation and ATP release induced by arachidonic acid, collagen or thrombin,
      with the IC(50) values of 5.4 to 76.8 muM. The thromboxane B(2) formation caused
      by collagen or thrombin was markedly inhibited by PC-09, but there was no
      alteration in that caused by arachidonic acid. The rise of platelet intracellular
      calcium level stimulated by aggregation agonists and collagen-induced platelet
      membrane surface glycoprotein IIb/IIIa expression was also reduced by PC-09. In
      addition, PC-09 itself significantly increased the cyclic AMP level through
      inhibiting cyclic AMP phosphodiesterase activity. These findings demonstrate that
      PC-09 is an inhibitor of platelet aggregation, which may be associated with
      mechanisms including inhibition of thromboxane A(2) formation, intracellular
      calcium mobilization and platelet surface GPIIb/IIIa expression accompanied by
      increasing cyclic AMP level.

PMID- 16457810
TI  - Different susceptibilities of PECAM-deficient mouse strains to spontaneous
      idiopathic pneumonitis.
AB  - Platelet Endothelial Cell Adhesion Molecule (PECAM) is an adhesion and signaling
      molecule used for leukocyte extravasation. We have generated two strains of PECAM
      deficient mouse, one in the original C57BL/6 and a second by backcrossing nice
      generations into the FVB/n strain. The FVB/n strain has reduced responses in
      models of acute inflammation. We show here that this strain is also susceptible
      to a chronic pneumonia which leads to pulmonary fibrosis. In contrast, PECAM
      deficient C57BL/6 mice do not develop this lung disease and have normal responses
      in acute models of inflammation. This demonstrates that PECAM-dependent and 
      independent mechanisms are found in both acute and chronic inflammation. Further,
      the PECAM-deficient FVB/n strain has many pathologic similarities to the human
      disease Idiopathic Pulmonary Fibrosis, suggesting that similar molecular
      mechanisms may play a role in human disease.

PMID- 16457811
TI  - Quantification of size distribution of restriction fragments in mitochondrial
      genome using fluorescence correlation spectroscopy.
AB  - A crucial investigation is to quantify restriction fragment length polymorphisms
      without gel electrophoresis, as the distribution of fragment size is mainly
      evaluated on the gel, which cannot be easily quantified. We developed a method to
      determine the fragmentation of the mitochondrial genome caused by restriction
      enzymes using fluorescence correlation spectroscopy (FCS). Distribution of
      fragment size was evaluated by the decrease in amplitude of the fluorescence
      correlation function while the mitochondrial genome PCR product was digested with
      Hga I or Hae III. Using a multicomponent model, which was considered as a
      fragment length-weighted correlation function, we calculated the correlation
      amplitude theoretically expected and compared it to that measured by FCS. These
      amplitudes for Hga I were coincident, whereas the measured amplitude for Hae III
      was more than the theoretical one. Because of tetra-nucleotide recognition by Hae
      III, there were many more fragments than with Hga I. Therefore, the amplitude
      measured by FCS would be a very useful index for primary screening for
      alterations in the entire mitochondrial genome with restriction enzymes that have
      several polymorphic restriction sites in the genome.

PMID- 16457812
TI  - Trypsins and their role in carcinoma growth.
AB  - There are more than 100 distinct types of cancer, and subtypes can be found
      within specific organs. Cancer progression is a complex multi-step process. These
      steps reflect alterations that drive the progressive transformation of normal
      cells into highly malignant ones. One critical step in tumor growth and invasion
      is the proteolytic processing of the extracellular matrix environment. The
      degradation of the extracellular matrix not only enables cell migration,
      invasion, and metastasis formation, but also affects cell behavior in multiple
      ways; on one hand by cleaving extracellular matrix bound growth factors and on
      the other hand by inhibiting angiogenesis into the tumor by liberating cryptic
      endogenous inhibitors of angiogenesis. Serine proteases and matrix
      metalloproteases are families of proteolytic enzymes involved in physiological
      and pathological extracellular matrix and basement membrane processing. In this
      review, we will focus on the role and activation of trypsinogens, a family of
      serine proteases, in cancer progression.

PMID- 16457813
TI  - MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis.
AB  - The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase
      pathway, also known as the MEK-ERK cascade, has been shown to regulate cartilage
      differentiation in embryonic limb mesoderm and several chondrogenic cell lines.
      In the present study, we employed the micromass culture system to define the
      roles of MEK-ERK signaling in the chondrogenic differentiation of neural crest
      derived ectomesenchyme cells of the embryonic chick facial primordia. In cultures
      of frontonasal mesenchyme isolated from stage 24/25 embryos, treatment with the
      MEK inhibitor U0126 increased type II collagen and glycosaminoglycan deposition
      into cartilage matrix, elevated mRNA levels for three chondrogenic marker genes
      (col2a1, aggrecan, and sox9), and increased expression of a Sox9-responsive
      collagen II enhancer-luciferase reporter gene. Transfection of frontonasal
      mesenchyme cells with dominant negative ERK increased collagen II enhancer
      activation, whereas transfection of constitutively active MEK decreased its
      activity. Thus, MEK-ERK signaling inhibits chondrogenesis in stage 24/25
      frontonasal mesenchyme. Conversely, MEK-ERK signaling enhanced chondrogenic
      differentiation in mesenchyme of the stage 24/25 mandibular arch. In mandibular
      mesenchyme cultures, pharmacological MEK inhibition decreased cartilage matrix
      deposition, cartilage-specific RNA levels, and collagen II enhancer activity.
      Expression of constitutively active MEK increased collagen II enhancer activation
      in mandibular mesenchyme, while dominant negative ERK had the opposite effect.
      Interestingly, MEK-ERK modulation had no significant effects on cultures of
      maxillary or hyoid process mesenchyme cells. Moreover, we observed a striking
      shift in the response of frontonasal mesenchyme to MEK-ERK modulation by stage
      28/29 of development.

PMID- 16457814
TI  - Peroxisome proliferator-activated receptor gamma regulates expression of signal
      transducer and activator of transcription 5A.
AB  - Signal transducer and activator of transcription 5A (STAT5A) has been shown to be
      important for terminal differentiation of mammary epithelial cells. In order to
      understand regulation of expression of STAT5A, the 5' end of the mouse Stat5a
      gene was isolated. Putative regulatory elements was searched for and several
      peroxisome proliferator response elements (PPREs) were found, one with high
      (12/13 nucleotides) and three with less (8-10/13) similarity to the reported
      consensus sequence. Mouse mammary epithelial HC11 cells were treated with
      peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, the
      thiazolidinedione (TZD) troglitazone, and an increase in STAT5A protein
      expression was seen. The 5' flank of Stat5a gene was cloned in a luciferase
      reporter vector. A concentration dependent activation of the STAT5A-luciferase
      reporter was detected, when transiently transfected HC11 cells were treated with
      TZD. The activation could be inhibited by treatment with a PPARgamma antagonist.
      It has earlier been shown that epidermal growth factor (EGF) induces MAPK
      phosphorylation of PPARgamma resulting in a less transcriptionally active
      receptor. In HC11 cells, EGF inhibited TZD induced STAT5A-reporter activity
      suggesting that our previously reported EGF-mediated suppression of STAT5A
      expression is mediated in all or partly through inhibition of PPARgamma activity.
      Furthermore, the MEK inhibitor PD98059 inhibited the EGF effect. All together,
      data presented suggest that PPARgamma participates in regulation of STAT5A
      expression.

PMID- 16457816
TI  - Rin1 regulates insulin receptor signal transduction pathways.
AB  - Rin1 is a multifunctional protein containing several domains, including Ras
      binding and Rab5 GEF domains. The role of Rin1 in insulin receptor
      internalization and signaling was examined by expressing Rin1 and deletion
      mutants in cells utilizing a retrovirus system. Here, we show that insulin
      receptor-mediated endocystosis and fluid phase insulin-stimulated endocytosis are
      enhanced in cells expressing the Rin1:wild type and the Rin1:C deletion mutant,
      which contain both the Rab5-GEF and GTP-bound Ras binding domains. However, the
      Rin1:N deletion mutant, which contains both the SH2 and proline-rich domains,
      blocked insulin-stimulated receptor-mediated and insulin-stimulated fluid phase
      endocytosis. In addition, the expression of Rin1:delta (429-490), a natural
      occurring splice variant, also blocked both receptor-mediated and fluid phase
      endocystosis. Furthermore, association of the Rin1 SH2 domain with the insulin
      receptor was dependent on tyrosine phosphorylation of the insulin receptor.
      Morphological analysis indicates that Rin1 co-localizes with insulin receptor
      both at the cell surface and in endosomes upon insulin stimulation.
      Interestingly, the expression of Rin1:wild type and both deletion mutants blocks
      the activation of Erk1/2 and Akt1 kinase activities without affecting either JN
      or p38 kinase activities. DNA synthesis and Elk-1 activation are also altered by
      the expression of Rin1:wild type and the Rin1:C deletion mutant. In contrast, the
      expression of Rin1:delta stimulates both Erk1/2 and Akt1 activation, DNA
      synthesis and Elk-1 activation. These results demonstrate that Rin1 plays an
      important role in both insulin receptor membrane trafficking and signaling.

PMID- 16457815
TI  - The retinitis pigmentosa-mutated RP2 protein exhibits exonuclease activity and
      translocates to the nucleus in response to DNA damage.
AB  - Retinitis pigmentosa (RP) is a genetically heterogeneous disease characterized by
      degeneration of the retina. Mutations in the RP2 gene are linked to the second
      most frequent form of X-linked retinitis pigmentosa. RP2 is a plasma membrane
      associated protein of unknown function. The N-terminal domain of RP2 shares amino
      acid sequence similarity to the tubulin-specific chaperone protein co-factor C.
      The C-terminus consists of a domain with similarity to nucleoside diphosphate
      kinases (NDKs). Human NDK1, in addition to its role in providing nucleoside
      triphosphates, has recently been described as a 3' to 5' exonuclease. Here, we
      show that RP2 is a DNA-binding protein that exhibits exonuclease activity, with a
      preference for single-stranded or nicked DNA substrates that occur as
      intermediates of base excision repair pathways. Furthermore, we show that RP2
      undergoes re-localization into the nucleus upon treatment of cells with DNA
      damaging agents inducing oxidative stress, most notably solar simulated light and
      UVA radiation. The data suggest that RP2 may have previously unrecognized roles
      as a DNA damage response factor and 3' to 5' exonuclease.

PMID- 16457818
TI  - Anthocyanins from soybean seed coat inhibit the expression of TNF-alpha-induced
      genes associated with ischemia/reperfusion in endothelial cell by NF-kappaB
      dependent pathway and reduce rat myocardial damages incurred by ischemia and
      reperfusion in vivo.
AB  - We examined the inhibition of the expression of some inflammatory genes
      associated with ischemia-reperfusion (I/R) injury by anthocyanins isolated from
      black soybean seed coat in tumor necrosis factor-alpha (TNF-alpha)-treated bovine
      aortic endothelial cells. In addition, its potential use on I/R-injury was
      investigated using rats subjected to 30-min occlusion of left descending coronary
      artery followed by 24-h reperfusion. Western blot analysis and luciferase
      activity assay showed that anthocyanins inhibited TNF-alpha-induced vascular cell
      adhesion molecule-1, intracellular adhesion molecule-1, and cyclooxygenase-2
      levels, which is through NF-kappaB-dependent pathway. Further, anthocyanins
      protected myocardiac injury from I/R in rats. It is suggested that anthocyanins
      from black soybean seed coat can be used as a useful drug to modulate
      cardiovascular disorder.

PMID- 16457817
TI  - TGF-beta 1-induced PAI-1 expression is E box/USF-dependent and requires EGFR
      signaling.
AB  - Transforming growth factor-beta1 (TGF-beta1) transcriptionally regulates the
      expression of genes that encode specific proteins (e.g., plasminogen activator
      inhibitor-1; PAI-1) important in stromal remodeling and cellular invasion.
      Definition of molecular events underlying TGF-beta1-initiated PAI-1
      transcription, therefore, may lead to the identification of new therapeutic
      targets for diseases associated with elevated PAI-1 synthesis (e.g., tissue
      fibrosis, vascular disorders, tumor progression). An intact upstream stimulatory
      factor (USF)-binding E box motif (5'-(-165)CACGTG(-160)-3') at the HRE-2 site in
      the rat PAI-1 gene was required for PAI-1 transcription in TGF-beta1-treated
      cells. Mutation of the CA dinucleotide to TC at position -165/-164 in a reporter
      construct driven by 764 bp of PAI-1 promoter sequence decreased TGF-beta1
      dependent CAT activity by >80% indicating the necessity for a consensus
      hexanucleotide E box motif in induced expression. The same CA --> TC substitution
      eliminated USF binding to an 18-bp HRE-2 DNA target highlighting the importance
      of site occupancy to transcriptional activation. Transfection of a dominant
      negative USF construct, moreover, completely inhibited formation of USF/HRE-2
      probe complexes, attenuated PAI-1 promoter-driven luciferase activity and reduced
      the response of the endogenous PAI-1 gene to TGF-beta1 (to that approximating
      quiescent controls). Maximal immediate-early PAI-1 induction upon exposure to TGF
      beta1 required EGFR, p21ras, MEK and pp60(c-src) signaling as pharmacologic or
      dominant-negative inhibition of any of the four intermediates (EGFR, p21ras, MEK,
      pp60(c-src)) virtually eliminated TGF-beta1-augmented PAI-1 levels. U0126
      titering experiments, furthermore, revealed that the same MEK inhibitor
      concentration that blocked the TGF-beta1 increase in ERK1/2 phosphorylation (20
      microM) also effectively attenuated the PAI-1 inductive response suggesting a
      requirement for stimulated ERK signaling in TGF-beta1-mediated PAI-1 expression.
      These data suggest a model whereby TGF-beta1 activates a complex signaling
      cascade to affect PAI-1 gene control and involves USF occupancy of a critical E
      box motif at the HRE-2 site in the PAI-1 gene.

PMID- 16457819
TI  - The Tie2 5' untranslated region is inhibitory to 5' end-mediated translation
      initiation.
AB  - Tie2 is an endothelium-specific receptor tyrosine kinase required for normal
      blood vessel maturation, remodeling, and stability. Tie2 expression is also
      upregulated in various cancers implicating a role in tumor angiogenesis. Its mRNA
      transcript contains an unusually long (372 nucleotides) 5' untranslated region
      (UTR) with five upstream open reading frames (uORFs) and an internal ribosome
      entry site (IRES) that allows this mRNA to be translated under hypoxic
      conditions. This sets up an alternative initiation pathway with the potential to
      clash with 5' end-mediated initiation from the same template. Herein, we define
      experimental conditions under which the Tie2 IRES is not active, allowing us to
      assess the contribution of the 5' UTR to cap-dependent translation on the Tie2
      transcript. We find that the Tie2 5' UTR is inhibitory to translation initiation
      with ribosome flow decreasing following encounters with each uORF. No single uORF
      was found to harbor significant cis-acting inhibitory activity. Our results
      suggest that the uORFs within the Tie2 5' UTR serve to decrease the percent of
      ribosomes competent for reinitiation as these traverse the mRNA 5' UTR, thus
      minimizing interference with the IRES.

PMID- 16457820
TI  - Identification of the linear epitope for Fc-binding on the bovine IgG2 Fc
      receptor (boFcgamma2R) using synthetic peptides.
AB  - To identify the linear epitope for Fc-binding on the bovine IgG2 Fc receptor
      (boFcgamma2R), peptides derived from the membrane-distal extracellular domain
      (EC1) of boFcgamma2R corresponding to the homologous region of human FcalphaRI
      were synthesized. Binding of bovine IgG2 to the different peptides was tested by
      Dot-blot assay, and the peptide showing maximal binding was further modified by
      truncation and mutation. The minimum effective peptide 82FIGV85 located in the
      putative F-G loop of the EC1 domain was found to bind bovine IgG2 specifically
      and inhibit the binding of bovine IgG2 to the receptor. The Phe82, Ile83 and
      Val85 residues within the linear epitope were shown to be critical for IgG2
      binding. Such functional epitope peptide should be very useful for understanding
      the IgG-Fcgamma interaction and development of FcR-targeting drugs.

PMID- 16457821
TI  - Arabidopsis GIGANTEA protein is post-transcriptionally regulated by light and
      dark.
AB  - GIGANTEA (GI) is a key regulator of photoperiodic flowering in Arabidopsis and
      encodes a protein with no domains of known biochemical function. Expression of GI
      mRNA is controlled by the circadian clock, but GI protein accumulation has not
      been previously investigated. We generated plants that produced functional
      epitope-tagged GI to enable us to track the protein through the daily cycle. Here
      we show that GI protein levels oscillate when either constitutively overexpressed
      or driven by its promoter and that its accumulation is modulated by day length as
      well as by phase-specific factors. Also, we demonstrate that one of the
      mechanisms underlying GI protein oscillation occurs post-translationally via dark
      induced proteolysis by the 26S proteasome.

PMID- 16457822
TI  - CT domain of CCN2/CTGF directly interacts with fibronectin and enhances cell
      adhesion of chondrocytes through integrin alpha5beta1.
AB  - Searching for CCN family protein 2/connective tissue growth factor (CCN2/CTGF)
      interactive proteins by yeast-two-hybrid screening, we identified fibronectin 1
      gene product as a major binding partner of CCN2/CTGF in the chondrosarcoma
      derived chondrocytic cell line HCS-2/8. Only the CT domain of CCN2/CTGF bound
      directly to fibronectin (FN). CCN2/CTGF and its CT domain enhanced the adhesion
      of HCS-2/8 cells to FN in a dose-dependent manner. The CCN2/CTGF-enhancing effect
      on cell adhesion to FN was abolished by a blocking antibody against alpha5beta1
      integrin (alpha5beta1), but not by one against anti-alphavbeta3 integrin. These
      findings suggest for the first time that CCN2/CTGF enhances chondrocyte adhesion
      to FN through direct interaction of its C-terminal CT domain with FN, and that
      alpha5beta1 is involved in this adhesion.

PMID- 16457823
TI  - The conserved Ala37 in the ERF/AP2 domain is essential for binding with the DRE
      element and the GCC box.
AB  - Four AP2/EREBP genes encoding putative ethylene-responsive element binding factor
      (ERF)/AP2 domains were cloned from Brassica napus, and these genes could be
      induced by low temperature, ethylene, drought, high salinity, abscisic acid and
      jasmonate treatments. These four genes, named BnDREBIII-1 to BnDREBIII-4, were
      highly homologous and the 37th amino acid was the only difference among their
      ERF/AP2 domains. BnDREBIII-1 was demonstrated to be able to bind to both
      dehydration-responsive element and the GCC box and transactivate the expression
      of downstream genes, while BnDREBIII-4 could bind neither. Further results
      suggested that Ala37 might play a crucial role in the DNA binding or the
      stability of the ERF/AP2 domain.

PMID- 16457824
TI  - Avian thyroid development and adaptive plasticity.
AB  - Precocial and altricial modes of avian development are characterized by different
      degrees of maturation and physiological capabilities at hatching. In precocial
      birds, thyroid function and its control are well developed during the latter part
      of incubation and hatchlings exhibit metabolic responses to cooling and
      relatively mature sensory and locomotor capabilities. In altricial birds, thyroid
      function shows little maturation until after hatch as also is the case for
      thermoregulatory, sensory, and motor functions. This review describes the
      patterns of precocial and altricial thyroid development, their hypothalamic
      pituitary control, extrathyroidal control of hormone activation and deactivation,
      and target tissue effects during development. Our knowledge is greatest for
      precocial galliform birds although the organismal picture of thyroid development
      has been investigated in several altricial avian species.

PMID- 16457825
TI  - Hormonal and behavioural symmetries between the sexes in the Northern bald ibis.
AB  - Seasonal patterns of fecal androgen and corticosteroid levels were measured in a
      semi-tame colony of Northern bald ibis (Geronticus eremita) and put in
      perspective with socio-sexual patterns. Northern bald ibis are monomorphic,
      monogamous, year-round social colonial breeders. Steroids levels were assessed
      from the pre-mating until the end of the mating season in the sexes, age groups,
      and social categories. Male immunoreactive androgen concentrations, determined by
      enzyme immuno-assay from feces, were relatively low, even during the mating
      phase, and were close to the female levels. Sexual monomorphy and symmetries in
      socio-sexual and parental roles may account for this similarity. Males and
      females responded in a similar way to social challenges from conspecifics,
      particularly during pair-formation. Singletons showed higher androgen metabolites
      levels than paired individuals. Corticosterone metabolites were relatively high
      during periods of social instability in the mating phase and were highest in low
      ranking, young individuals. We suggest that the challenge hypothesis may even
      apply to females in this non-passerine bird.

PMID- 16457827
TI  - Regulation of lipoprotein lipase activity in rainbow trout (Oncorhynchus mykiss)
      tissues.
AB  - Lipoprotein lipase (LPL) is considered as a key enzyme in the lipid deposition
      and metabolism of many tissues. Information on LPL activity and its regulation in
      fish remains very scarce. In the present study, we have examined the nutritional
      regulation of LPL activity by conducting post-feeding and fasting experiments in
      rainbow trout (Oncorhynchus mykiss). As insulin plays an important role in the
      nutritional regulation of LPL activity in mammals, the effects of this hormone
      were tested in vivo by intraperitoneal administration. Moreover, we conducted in
      vitro studies using fat pads of rainbow trout to better clarify the direct role
      of insulin and tumor necrosis factor-alpha (TNFalpha) as possible regulators of
      LPL activity in rainbow trout. LPL activity in adipose tissue increased in
      response to feeding, 4h after ingestion of food, then decreasing to basal levels
      at 6h. No clear response was found in either red or white muscles, where LPL
      values were lower. Moreover, fasting produced a down-regulation of LPL activity
      in adipose tissue, concomitant with low levels of plasma insulin. While insulin
      administration stimulated LPL activity of adipose tissue 3h after injection, no
      response was observed in red or white muscles. Finally, in vitro studies using
      fat pads revealed that insulin significantly stimulated the proportion of LPL in
      active conformation at the extracellular level. On the other hand, TNFalpha did
      not greatly affect LPL activity using this in vitro model. These data indicate
      that LPL activity is regulated in a tissue-specific manner following food intake,
      and suggest that insulin is an important regulator of LPL activity in the adipose
      tissue of rainbow trout.

PMID- 16457826
TI  - Molecular cloning and characterization of preproopiomelanocortin (prePOMC) cDNA
      from the ostrich (Struthio camelus).
AB  - To date proopiomelanocortin (POMC), the precursor protein for melanotropin (MSH),
      adrenocorticotropin (ACTH), lipotropins (LPH), and beta-endorphin (beta-END) in
      the pituitary gland, has been studied extensively over a wide spectrum of
      vertebrate classes. A paucity of information exists, however, with regard to POMC
      in the avian class, where to date POMC from only one species, the domestic
      chicken, appears to have been fully characterized. In the present study, we
      report the use of three clones of cDNA to provide the complete nucleotide
      sequence of ostrich prePOMC cDNA, consisting of 1072 bp (excluding the poly(A)
      tail). The deduced amino acid sequence of 253 amino acid residues includes the N
      terminal signal peptide of 17 amino acid residues. The predicted amino acid
      sequence in the overall arrangement of its domains, conforms to that found in
      other tetrapods. Sequence domains for gamma-MSH, ACTH, alpha-MSH, gamma-LPH, beta
      MSH, and beta-END are located at positions 74-85, 134-172, 134-146, 175-220, 203
      220, and 223-253, respectively, in ostrich prePOMC, but some of them may not be
      released in the ostrich pituitary gland, despite the presence of nine potential
      processing sites consisting of 2-4 dibasic amino acids each. Substitution of
      glutamic acid for a dibasic amino acid at position 202 in ostrich prePOMC could
      prevent release of beta-MSH. To date the release of pro-gamma-MSH, beta-LPH,
      ACTH, gamma-LPH, and beta-END have been confirmed by direct isolation and
      characterization from ostrich pituitary extracts. In the present study, we have
      also identified ACTH, gamma-LPH and beta-END in a single frozen ostrich pituitary
      slice by means of MALDI-TOF mass spectrometry. When compared to a wide range of
      vertebrate prePOMC molecules, ostrich prePOMC revealed a high level of amino acid
      sequence identity (77%) with chicken prePOMC, which is the only other avian
      sequence available. As with other vertebrate classes, considerable intraclass
      differences were also evident between chicken and ostrich prePOMCs, which belong
      to different avian orders. Identity of ostrich prePOMC with non-avian tetrapod
      counterparts is only moderate (53-56%), whereas lower identities (20-49%) are
      evident over a range of fish prePOMCs.

PMID- 16457828
TI  - Hormonal control of salt and water balance in vertebrates.
AB  - The endocrine system mediates many of the physiological responses to the
      homeostatic and acclimation demands of salt and water transport. Many of the
      hormones involved in the control of salt and water transport are common to all
      vertebrates, although their precise function and target tissues have changed
      during evolution. Arginine vasopressin (vasotocin), angiotensin II, natriuretic
      peptides, vasoactive intestinal peptide, urotensin II, insulin and non-genomic
      actions of corticosteroids are involved in acute (minutes and hours) alterations
      in ion and water transport. This rapid alteration in transport is primarily the
      result changes in behavior, blood flow to osmoregulatory organs, and membrane
      insertion or activation (e.g., phosphorylation) of existing transport proteins,
      ion and water channels, contransporters and pumps. Corticosteroids (through
      genomic actions), prolactin, growth hormone, and insulin-like growth factor I
      primarily control long-term (several hours to days) changes in transport capacity
      that are the result of synthesis of new transport proteins, cell proliferation,
      and differentiation. In addition to the important task of establishing broad
      evolutionary patterns in hormones involved in ion regulation, comparative
      endocrinology can determine species and population level differences in signaling
      pathways that may be critical for adaptation to extreme or rapidly changing
      environments.

PMID- 16457829
TI  - Maternal androgens in eggs of communally breeding guira cuckoos (Guira guira).
AB  - Variation of maternal androgens in avian eggs may be a mechanism of maternal
      influence on offspring development, growth, and/or behavior. We studied yolk
      androgen concentrations in eggs of guira cuckoos (Guira guira) to understand how
      females might enhance the success of offspring in a complex communal breeding
      system. We measured concentrations of androstenedione, 5alpha
      dihydrotestosterone, and testosterone in yolks and identified eggs and clutches
      of individuals in joint nests by yolk protein electrophoresis. Androstenedione
      had the highest yolk concentration, at least 10 times higher than that of
      testosterone and 5alpha-dihydrotestosterone. The first eggs of individual females
      that laid two or three eggs in a joint nest had lower androstenedione
      concentrations than their second and third eggs, the latter having a lower
      probability of being ejected from the nest. This implies that guira cuckoo
      females may influence offspring survival and competitiveness in communal nests by
      means of differential allocation of androstenedione and laying tactics. There was
      significant variation in yolk androstenedione among females, but the order in
      which females entered laying in the communal clutch had no effect on the
      concentrations. Androstenedione yolk concentrations increased with communal
      clutch size, which may indicate that higher levels of competition in larger
      groups lead to higher yolk androgen concentrations. Finally, androstenedione
      concentrations were higher in clutches in the later wetter periods of the rainy
      season than during the earlier drier period. This may be explained by the high
      frequency of large clutches in the later periods, with more females contributing
      to a joint clutch.

PMID- 16457830
TI  - The isolation and purification of glucoraphanin from broccoli seeds by solid
      phase extraction and preparative high performance liquid chromatography.
AB  - Plant foods contain not only essential nutrients, e.g. protein, amino acids,
      vitamins and minerals, but also phytochemicals that have added health benefits.
      One such class of phytochemicals are the glucosinolates. Glucosinolates,
      particularly glucoraphanin, are predominant in plants of the Brassica genus, most
      notably in vegetables such as broccoli. There is a growing interest in the role
      glucoraphanin plays in chemoprotection and as a result there is a requirement to
      accurately determine the levels of glucoraphanin in vegetable products. Reverse
      phase ion pair high performance liquid chromatography (HPLC) is the method of
      choice; however, this work has been hindered by the lack of available standard
      reference materials. Broccoli seeds, which are particularly rich in glucoraphanin
      (20-50 mg/g), have proved to be ideal for the isolation of glucoraphanin on the
      preparative scale. A novel preparative scale HPLC method with simple compound
      recovery has been developed to meet the need for a glucoraphanin standard.

PMID- 16457831
TI  - Pressurized liquid extraction of polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans and coplanar polychlorinated biphenyls from
      contaminated soil.
AB  - Extraction solvents for pressurized liquid extraction (PLE) used to extract
      polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans (PCDD/PCDFs),
      and coplanar polychlorinated biphenyls (Co-PCBs) from contaminated soil were
      investigated. The PCDD/PCDFs and Co-PCBs in Certified Reference Material: CRM
      0422 (Forest soil) were extracted using toluene, n-hexane, acetone,
      acetone/toluene and acetone/n-hexane (1:1, v/v). Soxhlet extraction was the
      reference method. Results demonstrated that PLE using mixed solvents produced
      better analyte recoveries than the single solvents. However, these results were
      lower than those for Soxhlet extraction. Additional extraction cycles using mixed
      solvents achieved better recovery results. Mixed solvents and several extraction
      cycles were necessary for satisfactory extraction of more tightly bound
      PCDD/PCDFs and Co-PCBs from soil.

PMID- 16457832
TI  - Cyclodextrin-modified microemulsion electrokinetic chromatography for separation
      of alpha-, gamma-, delta-tocopherol and alpha-tocopherol acetate.
AB  - Different forms of tocopherols, together with tocotrienols, are collectively
      named as vitamin E, and each possesses different degree of medical, biological
      and physiochemical significance. The main difficulty of separating different
      forms of tocopherols lay in their highly structural similarities and
      hydrophobicities. Microemulsion electrokinetic chromatography (MEEKC), claimed to
      attain high peak efficiency with great solubilization power, has not previously
      been applied to the separation of tocopherols. The effects that various
      parameters, such as buffer system, type and concentration of cyclodextrins,
      temperature, and sample matrix, have on the separation of tocopherols by MEEKC
      have been investigated. By using a buffer mixture of 4% (w/w) sodium dodecyl
      sulfate (SDS), 6.6% (w/w) 1-butanol, 0.8% (w/w) n-octane, 20% (w/w) 2-propanol,
      68.6% (w/w) phosphate (25mM, pH 2.5), and 25mM heptakis(2,6-di-O-methyl)-beta
      cyclodextrin (DM-beta-CD), the separation of alpha-, gamma-, and delta
      tocopherol, alpha-tocopherol acetate, as well as the antioxidant butylated
      hydroxytoluene (BHT) at -26kV, 25 degrees C was completed within 35min. The
      practical potential of the present approach has been further validated by the
      determination of tocopherols in a vitamin E preparation, with the result of
      132.63 (RSD 1.25%), 176.51 (RSD 0.29%), and 64.32mg (RSD 3.34%) per 500mg capsule
      for alpha-, gamma- and delta-tocopherol, respectively.

PMID- 16457833
TI  - Dioctadecyldimethylammonium bromide vesicles prepared by the surfactant removal
      method.
AB  - Dioctadecyldimethylammonium bromide (DODAB) is a double chain vesicle-forming
      cationic surfactant, whereas octa-ethyleneglycol mono-n-dodecyl ether (C12E8) is
      a single chain micelle-forming nonionic surfactant. At room temperature (ca. 22
      degrees C) C12E8 molecules self-assemble in water as micelles while DODAB is
      insoluble. A mixture of DODAB and C12E8, however, can be soluble in water at room
      temperature depending on the relative amount of the compounds. We report the
      formation of small unilamellar vesicles (SUVs) by dialyzing at room temperature a
      mixture of 1.0 mM DODAB with 10 mM C12E8 in water. Extended bilayers are formed
      as well in equilibrium with vesicles. Such structures are viewed by a cryogenic
      transmission electron microscopy (cryo-TEM) image.

PMID- 16457834
TI  - Characterization of the reactivity of a silica derived from acid activation of
      sepiolite with silane by 29Si and 13C solid-state NMR.
AB  - The mechanism of the reaction between a silica sample coming from acid treatment
      of sepiolite (denominated Silsep) and an organosilane, namely
      bis(triethoxysilylpropyl)tetrasulfane (TESPT), has been evaluated by solid state
      NMR spectroscopy, being compared with the silanization reaction of a commercial
      silica. The effect of the silane concentration and temperature on the course of
      the reaction was considered. Experimental results indicate that the silanization
      reaction is more effective in the case of Silsep, favoring both the reaction of
      silane molecules with the filler surface and the reaction between neighboring
      silane molecules. This different behavior is attributed to structural factors,
      moisture, and number of acid centers on silica surface. Environmental scanning
      electron microscopy (ESEM) was used to deposit micrometric water drops on the
      surface of these samples and to evaluate the proportion and distribution of the
      organophylization process.

PMID- 16457835
TI  - Intrinsic viscosity of SiO2, Al2O3 and TiO2 aqueous suspensions.
AB  - The viscosity of dilute suspensions of several metal oxides (SiO2, Al2O3 and
      TiO2) was measured at different pH values. The intrinsic viscosity, [eta], was
      derived from the concentration dependence of the viscosity. This magnitude was pH
      dependent. A correlation with the shape of the kinetic unity has been proposed.

PMID- 16457836
TI  - Synthesis and characterization of surface-enhanced Raman scattering tags with
      Ag/SiO2 core-shell nanostructures using reverse micelle technology.
AB  - A novel simplified method for synthesis of surface-enhanced Raman scattering tags
      has been reported. This synthesis method is based on reverse micelle technique
      using Igepal CO-520 as a surfactant and the mixed solution of silver nitrate and
      rhodamine dyes with isothiocyanate group as water pool followed by hydrazine
      hydrate reduction and TEOS polymerization leading to the formation of silica
      layer surrounding the silver core. Compared to the method reported in literature,
      the proposed methodology eliminates the necessity of vitrophilic pretreatment and
      makes it possible to complete all different processes including the preparation
      of silver nanoparticles, the conjugation of dye molecules and the formation of
      silica shell in the microreactor. The nanoparticle-based surface-enhanced Raman
      tags obtained are composed of silver core conjugated with rhodamine dyes and an
      encasing silica shell. Both the dyes themselves and the Ag/SiO2 core-shell
      nanoparticles without the encapsulation of dyes exhibit no Raman signals.
      However, the Ag/SiO2 core-shell nanoparticles exhibit strong Raman signals when
      encapsulated with these dyes. This is due to the appearance of fluorescence
      quenching and surface-enhanced Raman scattering effect resulting from the
      conjugation of dyes and silver core. The Raman tags were characterized using
      transmission electron microscopy (TEM), UV-visible absorption spectrometry, and
      Raman spectrometry.

PMID- 16457837
TI  - Sodium dodecyl sulfate promoting a cooperative association process of sodium
      cholate with bovine serum albumin.
AB  - Sodium cholate (NaC) was used as a representative bile salt in the process of
      cooperative binding to bovine serum albumin (BSA) in a mixture with sodium
      dodecyl sulfate (SDS). The experiments were performed in 0.02 M Tris-HCl buffer
      solution (pH 7.50), in the presence of 0.1% BSA and at 25 degrees C. The aim of
      this study is to provide information on the performance of the BSA in the
      promotion of cooperative binding of sodium cholate promoted by the presence of
      SDS. The method used to monitor the binding was based on the analysis of the
      effect of SDS and NaC concentrations and their mixtures upon the fluorescence
      intensity of the BSA tryptophan residues. Plots of the fluorescence emission
      bands in terms of the A0/A ratio vs surfactant concentrations, where A0 and A
      represent the areas of emission bands in the presence and absence of the
      surfactants, respectively, were drawn in order to investigate the surfactant
      interaction with the protein. An alternative methodology, the specific
      conductivity vs surfactant concentration plots, was used, which involves mixtures
      of SDS and NaC to investigate the association processes, through the
      determination of the critical aggregation concentration (cac, when in the
      presence of protein) and the critical micellar concentration (cmc). The results
      led to a general conclusion that as the mixed micellar aggregates become richer
      in the bile salt monomer, the tendency to lose the reactivity with the protein
      increases. According to our results, a clear evidence of the predomination of BSA
      SDS-NaC complexes is found only for the SDS molar fraction above approximately
      0.6, and below this fraction a tendency toward free mixed micelles starts to
      predominate.

PMID- 16457838
TI  - Large-scale synthesis of tungsten oxide nanofibers by electrospinning.
AB  - We show in this communication that large-scale synthesis of orthorhombic WO3
      nanofibers can be obtained via a simple electrospinning method. The morphology
      and the crystal structure are investigated by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), FTIR, X-ray diffraction patterns (XRD)
      and X-ray photoelectron spectra (XPS) spectra. SEM and TEM images showed that the
      diameter of the obtained WO3 nanofibers is between 100 and 500 nm. The structure
      of the obtained WO3 nanofibers was characterized by FTIR, XRD, and XPS spectra.
      The photoluminescence of the obtained WO3 nanofibers were also investigated.

PMID- 16457839
TI  - Effect of the ionic surfactant concentration on the stabilization/destabilization
      of polystyrene colloidal particles.
AB  - One of the most interesting properties of the surfactants is that they are able
      to alter the stability of colloidal dispersions. Despite its great industrial
      relevance, only a few works analyze the colloidal stability of these systems at
      high surfactant concentrations (well above the critical micelle concentration
      (CMC)). In the present work, the colloidal stability of polystyrene particles is
      studied under a wide range of ionic surfactant concentrations. The effects of the
      surface charge of the latex particles (evaluating both sign and value), and
      surfactant type (cationic or anionic) have been examined. Colloidal stability
      data have been gathered by monitoring aggregation using a nephelometric
      technique. As will be shown, it is possible to reach different stability regimes
      using the same colloidal system just by changing the surfactant concentration.
      Independently of the sign of both the surfactant and the surface, the
      destabilization of the system consistently takes place above certain surfactant
      concentration due to a depletion effect from non-adsorbed micelles. This
      destabilization can be predicted by adding to the DLVO interaction energy a new
      contribution addressing the force between two spherical particles in the presence
      of non-adsorbing spherical macromolecules.

PMID- 16457840
TI  - Local film thinning due to concentration gradient of an insoluble surfactant at
      an interface.
AB  - The local thinning of a viscous liquid film on a substrate driven by a surface
      (or interfacial) tension gradient due to a concentration gradient of a monolayer
      of an insoluble surfactant initially non-uniformly distributed at a liquid
      interface relevant to chemical engineering, biomedical and other applications is
      investigated. A simple model is presented for the temporal evolution of the
      profiles of radial variation in the thickness of a thin liquid film, the effects
      of gravity and capillarity due to deformation of the interface in slowing down
      the film thinning process being allowed. As time increases, the surfactant
      spreads and the radius of its front increases inversely with decrease in the two
      third power of the film thickness at the center. The model describes well not
      only the published experimental results but also those obtained by other authors
      using numerical simulations of a set of coupled partial differential equations.

PMID- 16457841
TI  - Kinetic computational alanine scanning: application to p53 oligomerization.
AB  - We have developed a novel computational alanine scanning approach that involves
      analysis of ensemble unfolding kinetics at high temperature to identify residues
      that are critical for the stability of a given protein. This approach has been
      applied to dimerization of the oligomerization domain (residues 326-355) of tumor
      suppressor p53. As validated by experimental results, our approach has reasonable
      success in identifying deleterious mutations, including mutations that have been
      linked to cancer. We discuss a method for determining the effect of mutations on
      the location of the dimerization transition state.

PMID- 16457842
TI  - Decoy models for protein structure comparison score normalisation.
AB  - A method is described to construct sets of decoy models that can be used to
      generate a background score distribution for protein structure comparison. The
      models are derived directly from the two proteins being compared and retain all
      the essential properties of the structures, including length, density, shape and
      secondary structure composition but have different folds. As each comparison
      involves a pair of proteins of the same length, no explicit normalisation is
      required to adjust for the length of the proteins being compared. This allows
      substructure (or domain) matches to score almost equally to the comparison of
      isolated domains. A normalised probability measure was derived that allows joint
      family/family comparison. The method was applied to some of the CASP6 models for
      targets with new folds.

PMID- 16457843
TI  - The effect of A2A adenosine receptor agonist on composite tissue allotransplant
      survival: an in vivo preliminary study.
AB  - BACKGROUND: In vitro experimental studies showed that A2a receptor agonists
      reduce allostimulatory functions of the dendritic cells through modulation of
      surface expression of the costimulatory molecules and down-regulation of
      cytokines. Similar suppressive effects on dendritic cells have also been observed
      with Cyclosporine A (CsA). In this study we sought to explore if combined use of
      these two drugs in vivo could prolong the survival of composite tissue allografts
      across MHC barriers. MATERIALS AND METHODS: A total of 24 hindlimb
      transplantations were performed across a major MHC barrier from Brown Norway rats
      (BN; RT1n) to Lewis rats (Lew; RT1l) In the control group, either isografts
      (group 1, n = 2) or allografts (group 2, n = 3) were performed and no treatment
      was given. In the experimental group three kinds of treatment protocols were
      used: (1) A2a adenosine receptor agonist alone (group 3, n = 6); (2) CsA alone
      (group 4, n = 7); and (3) A2a adenosine receptor agonist + CsA combined treatment
      (group 5, n = 6). Mean survival times of each group as well as cytokine levels
      including IL-2, IL-4, IL-10, INF-gamma, and TNF-alpha were analyzed by ELISA.
      RESULTS: Isografts survived indefinitely. The mean survival times for allograft
      groups (group 2 to 5) were 9.8 +/- 1.3, 10.5 +/- 1.0, 29.8 +/- 1.7, and 22 +/-
      1.4 days, respectively. Statistically, there was no difference between the
      allograft control group and the A2a adenosine receptor agonist treated group (P =
      0.35). However, survival of the allografts in the CsA-treated group was
      significantly higher than the A2a adenosine receptor agonist treated (P < 00001)
      and combined CsA + A2a adenosine receptor agonist treated group (P < 0.0001). In
      vivo A2a adenosine receptor agonist treatment alone increased the levels of IL-2,
      INF-gamma, and TNF-alpha, which are important cytokines for induction of
      allotransplant rejection. However A2a adenosine receptor agonist in combination
      with CsA significantly reduced the levels of suppressor cytokines IL-4 and IL-10.
      CONCLUSION: As opposed to the previous in vitro studies, the results from this in
      vivo study showed that A2a adenosine receptor agonist treatment does not prolong
      composite tissue allograft survival. Compared to CsA treatment alone, the
      allotransplant survival was even shorter with the combined treatment. Treatment
      with A2a adenosine receptor agonist possibly promotes the differentiation of
      alloreactive CD4 cells predominantly into T-helper 1 phenotype. As a result, the
      levels of stimulatory cytokines contributing to allograft rejection are increased
      and suppressor cytokines are reduced, leading to accelerated allograft rejection.

PMID- 16457844
TI  - Prospective evaluation of oral gastrografin in postoperative small bowel
      obstruction.
AB  - BACKGROUND: Orally administered gastrografin has been used for early resolution
      of postoperative small bowel obstruction (POSBO) and to reduce the need for
      surgery in various studies. However the studies have reported conflicting results
      as patients with complete obstruction and equivocal diagnosis of bowel
      strangulation were also included. PATIENTS AND METHODS: We carried out a
      prospective study to evaluate the efficacy of gastrografin in patients with
      partial adhesive small bowel obstruction. Patients with suspected strangulation,
      complete obstruction, obstructed hernia, bowel malignancy, and radiation
      enteritis were excluded. Sixty-two patients with partial adhesive small bowel
      obstruction were given an initial trial of conservative management of 48 h.
      Thirty-eight patients improved within 48 h and the other 24 were given 100 ml of
      undiluted gastrografin through the nasogastric tube. In 22 patients the contrast
      reached the colon within 24 h. In the remaining two patients the contrast failed
      to reach the colon and these underwent surgery. RESULTS: The use of gastrografin
      avoided surgical intervention in 91.3% (22 of 24) patients who failed
      conservative management of POSBO. Gastrografin also decreased the overall
      requirement for surgical management of POSBO from the reported rate of 25 to 30%
      to 3.2% (2 of 62). CONCLUSION: Use of gastrografin in patients with partial POSBO
      helps in resolution of symptoms and avoids the need for surgical management in
      the majority of patients.

PMID- 16457845
TI  - The solid-pseudopapillary tumor of pancreas: the clinical characteristics and
      surgical treatment.
AB  - BACKGROUND AND OBJECTIVE: Since being named and reclassified by WHO in 1996,
      solid-pseudopapillary tumor (SPT) of pancreas has been recognized as a special
      entitative disease that is different from pancreatic cancer and should be
      recognized and treated more accurately in the surgical process. The clinic
      characteristics and surgical strategy on 25 cases of SPT of pancreas from the
      authors' center are discussed. METHODS: The clinical pathology and the surgical
      methods of 25 SPTs were retrospectively studied. The analyses were performed by
      the statistical software package SAS6.12. RESULTS: No tumor recurrences were
      found in all patients. There was significant difference between operative types
      in radical resection and the tumor position of the pancreas (P = 0.0011). The
      judgment on the tumor's boundary could directly affect the adoptable operative
      types (P = 0.0099). CONCLUSIONS: As a uniquely entitative disease, SPT is a kind
      of uncommon neoplasm with low-grade malignancy with a strong rate of occurrence
      in women. Surgical resection is most favorable in the treatment of SPT, which has
      excellent prognosis. The course of SPT, the possible malignant cells by the
      frozen section biopsy, and the tumor's boundary are important for operators to
      decide an operative scheme. SPT that has infiltrated contiguous vessels, organs,
      even with local liver metastasis should not be regarded as operative
      contraindication. The choice of the local tumor resection, the part of pancreas
      resection or radical resection depends on the judgment of the tumor's boundary,
      whereas operative types in radical resection depend on the tumor position of the
      pancreas.

PMID- 16457846
TI  - Formation and prevention of postoperative abdominal adhesions.

PMID- 16457847
TI  - Role of antithrombin and factor XIII in leukocyte-independent plasma
      extravasation during endotoxemia: an intravital-microscopic study in the rat.
AB  - BACKGROUND: Platelet-endothelial interactions have been shown to be main
      mediators of leukocyte-independent endothelial damage. Besides altering platelet
      endothelial interactions, both antithrombin and factor XIII reduce microvascular
      permeability in leukocyte-dependent experimental models. Thus, it was our aim to
      investigate the effects of antithrombin and factor XIII on microvascular
      permeability during leukocyte-independent endotoxemia. MATERIAL AND METHODS: In
      male Wistar rats, venular wall shear rate, macromolecular efflux, and leukocyte
      endothelial interaction were determined in mesenteric postcapillary venules using
      intravital microscopy at baseline, 60, and 120 min after the start of the
      experiment. Fucoidin and a continuous infusion of lipopolysaccharides were used
      to generate leukocyte-independent endotoxemia. The experiment was divided into
      two parts 1) an antithrombin study and 2) a factor XIII study. RESULTS: No
      differences between groups in leukocyte rolling and venular wall shear rate could
      be observed in both parts of the experiment. Pretreatment with antithrombin
      reduced microvascular permeability significantly compared with control subjects
      (120 min: Fuco [untreated]: 0.14 +/- 0.03; Fuco/ETX [control]: 0.37 +/- 0.06;
      Fuco + ATIII/ETX: 0.15 +/- 0.02; P < 0.05). Factor XIII reduced microvascular
      permeability significantly after 60 min (Fuco [untreated]: 0.10 +/- 0.03;
      Fuco/ETX [control]: 0.36 +/- 0.07; Fuco + FXIII/ETX: 0.13 +/- 0.04; P < 0.05).
      This effect diminished after 120 min (Fuco [untreated]: 0.12 +/- 0.03; Fuco/ETX
      [control]: 0.5 +/- 0.08; Fuco + FXIII/ETX: 0.29 +/- 0.05; P < 0.05). CONCLUSIONS:
      Antithrombin and factor XIII reduce leukocyte-independent microvascular
      permeability. Yet, factor XIII also shows a nonprotective effect on a long-term
      basis. These data emphasize the central role of platelets in leukocyte
      independent endotoxemia.

PMID- 16457848
TI  - COX-2 induces IL-11 production in human breast cancer cells.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed in 40% of human invasive
      breast cancers. Interleukin-11 (IL-11), a potent mediator of osteoclastogenesis,
      is involved in breast cancer metastasis to bone. Since breast cancers that
      overexpress COX-2 are associated with a higher rate of metastasis to bone, we
      hypothesized that COX-2 expression in tumor cells would induce IL-11. MATERIALS
      AND METHODS: We transfected MCF-7 (poorly metastatic) and MDA-231 (highly
      metastatic) human breast cancer cell lines with COX-2 expression vectors. COX-2
      overexpression was confirmed by Western blot and PGE(2) immunoassay, and IL-11
      production was measured by immunoassay. We also used a nude mouse model to study
      COX-2 and IL-11 production from breast cancer cells that metastasized to bone.
      The bone-seeking clones (BSC) were isolated and cultured from the long bone
      metastases. RESULTS: COX-2 transfection caused an approximately 5- to 6-fold
      increase in IL-11 production in both MCF-7 and MDA-231 cells. MDA-435S-COX2-BSC
      (cells isolated from bone metastasis) produced elevated levels of IL-11 and PGE2
      (an important mediator of COX-2) as compared to the parental MDA-435S-COX2 cells.
      Furthermore, a treatment with low 1- to 2-microm concentration NS-398 or
      Celecoxib significantly reduced the production of IL-11 in COX-2-transfected MDA
      231 cells, thus confirming the involvement of COX-2 in IL-11 induction.
      CONCLUSION: COX-2-mediated production of IL-11 in breast cancer cells may be
      vital to the development of osteolytic bone metastases in patients with breast
      cancer, and a COX-2 inhibitor may be useful in inhibiting this process.

PMID- 16457849
TI  - Neuroprotective effects of L-carnitine and vitamin E alone or in combination
      against ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Neurological injury because of transient cerebral ischemia is a
      potential complication of cardiovascular surgery. In this study, the
      neuroprotective effects of L-carnitine, vitamin E, and the combination of these
      agents on ischemia/reperfusion (I/R) injury were determined in a rat model of
      transient global cerebral I/R. METHODS: Rats were pretreated with L-carnitine
      (100 mg/kg, i.v.) and vitamin E (50 mg/kg, i. v.), alone or in combination and
      then subjected to cerebral I/R induced by a four-vessel-occlusion technique for a
      duration of 15 min followed by 15 min of reperfusion. Malondialdehyde (MDA)
      levels, superoxide dismutase (SOD) activity, and glutathione (GSH) levels were
      measured in the cerebral tissues. Histopathological examinations were also
      carried out under light and electron microscopy. RESULTS: The results showed that
      I/R elevated MDA levels, which were accompanied by a reduction in SOD activities
      and GSH levels. Surviving neurons was markedly decreased in CA1 and CA3 subfield
      of hippocampus in I/R animals. L-carnitine, vitamin E, and their combination
      restored MDA levels and SOD activities, with a tendency to increase surviving
      neurons in CA1 and CA3 subfield. Combined treatment of L-carnitine and vitamin E
      had better GSH levels than individual treatment of these agents. CONCLUSIONS: The
      results suggest that L-carnitine has a potent neuroprotective effect against
      cerebral-I/R-induced injury in rat brain that is comparable to that of vitamin E.
      However, the combined use of L-carnitine and vitamin E does not further protect
      from neuronal injury, although it provides an increase in GSH levels.

PMID- 16457850
TI  - Fatigue and therapeutic exercise.
AB  - Fatigue is a common symptom in patients with neurologic disease. Mechanisms of
      fatigue are still incompletely understood. In this paper, we review recent
      studies of fatigue in common neurologic conditions and discuss therapeutic
      interventions. In particular, the role of therapeutic exercise is examined in
      both health and disease.

PMID- 16457851
TI  - Creatine prevents behavioral alterations caused by methylmalonic acid
      administration into the hippocampus of rats in the open field task.
AB  - Although a variable degree of psychomotor delay/mental retardation is found in a
      considerable number of patients affected by methylmalonic acidemia, the
      mechanisms underlying the neuropathology of this disorder are still poorly
      defined. The present study investigated the effect of acute intrahippocampal
      administration of methylmalonic acid (MMA), the biochemical hallmark of this
      disease, on rat behavior in the open field task. Cannulated 60-day-old male
      Wistar rats received bilateral intrahippocampal injection of MMA (0.1-1.0
      micromol) 10 min before training. Controls received 0.1-1.0 micromol NaCl.
      Testing session was performed 24 h later. We observed that rats administered with
      1.0 micromol MMA, but not with lower doses, did not habituate in the open field
      task, reflecting a deficit of performance. Motor activity, assessed by the number
      of crossing responses, was the same at training for the groups infused with MMA
      or NaCl. The effect of MK-801 (15 nmol) and succinate (1.5 micromol) administered
      30 min before MMA injection, and of creatine (50 mg/kg, i.p.) administered twice
      a day for 3 days on the behavioral alterations provoked by MMA in the open field
      task revealed that only the energetic substrate creatine prevented these effects,
      reflecting a possible compromise of brain energy production by MMA. The results
      indicate that high intrahippocampal concentrations of the major metabolite
      accumulating in methylmalonic acidemia compromises brain functioning, causing
      deficit of performance in the open field task that may be related to the
      psychomotor delay/mental retardation observed in the affected patients.

PMID- 16457852
TI  - A flexible computational framework for detecting, characterizing, and
      interpreting statistical patterns of epistasis in genetic studies of human
      disease susceptibility.
AB  - Detecting, characterizing, and interpreting gene-gene interactions or epistasis
      in studies of human disease susceptibility is both a mathematical and a
      computational challenge. To address this problem, we have previously developed a
      multifactor dimensionality reduction (MDR) method for collapsing high-dimensional
      genetic data into a single dimension (i.e. constructive induction) thus
      permitting interactions to be detected in relatively small sample sizes. In this
      paper, we describe a comprehensive and flexible framework for detecting and
      interpreting gene-gene interactions that utilizes advances in information theory
      for selecting interesting single-nucleotide polymorphisms (SNPs), MDR for
      constructive induction, machine learning methods for classification, and finally
      graphical models for interpretation. We illustrate the usefulness of this
      strategy using artificial datasets simulated from several different two-locus and
      three-locus epistasis models. We show that the accuracy, sensitivity,
      specificity, and precision of a naive Bayes classifier are significantly improved
      when SNPs are selected based on their information gain (i.e. class entropy
      removed) and reduced to a single attribute using MDR. We then apply this strategy
      to detecting, characterizing, and interpreting epistatic models in a genetic
      study (n = 500) of atrial fibrillation and show that both classification and
      model interpretation are significantly improved.

PMID- 16457853
TI  - Dietary supplement Standard Reference Materials.
AB  - A new category of Standard Reference Materials (SRMs) based on dietary
      supplements is under development by the National Institute of Standards and
      Technology (NIST), with certified values for organic constituents and selected
      trace elements. These materials are provided primarily for use in method
      development and as control materials. The SRMs will assist manufacturers of
      dietary supplements in characterizing raw materials for potency, authenticity,
      and contamination or adulteration. In addition, the SRMs will assist in
      assessment of consistency and quality in finished products. The goal of this
      ongoing effort is to provide tools to the dietary supplement industry and
      measurement communities that will lead to improved quality of dietary
      supplements, and ultimately reduce public health risks that could potentially be
      associated with these products.

PMID- 16457855
TI  - Propolis protects human spermatozoa from DNA damage caused by benzo[a]pyrene and
      exogenous reactive oxygen species.
AB  - Many environmental, physiological and genetic factors have been implicated in
      defective sperm function, the most common cause of infertility. In addition,
      sperm preparation techniques such as centrifugation, used prior to in vitro
      fertilization, are associated with the generation of reactive oxygen species
      (ROS) and an increase in the level of DNA damage. Factors that can offer
      spermatozoa protection are, therefore, of great importance. This study was
      designed to examine in vitro the effect of a Chilean propolis ethanolic extract
      on human spermatozoa treated with benzo[a]pyrene and exogenous reactive oxygen
      species. Our experimental evidence demonstrated that the natural drug under
      investigation is able to protect genomic DNA by damage induced by benzo[a]pyrene,
      hydrogen peroxide (H2O2) and hydrogen peroxide in combination with adenosine 5'
      diphosphate (ADP) and ferrous sulfate (FeSO4), determining a significant
      reduction of the intracellular oxidants. An increase in membrane damage, measured
      by monitoring the formation of thiobarbituric acid-reactive substances (TBARS)
      and lactic dehydrogenase (LDH) release, was observed only in sperm treated with
      H2O2, ADP and FeSO4. The propolis extract was shown to possess the capacity to
      protect sperm membrane from the deleterious action of oxidative attack, reducing
      TBARS formation and LDH release. In summary, our results evidence that the
      protective effect exhibited by this natural compound in human spermatozoa is
      correlated, at least in part, to the antioxidant capacity of its active
      components, and suggest that propolis may have a role in protection against male
      infertility.

PMID- 16457854
TI  - Pyruvate provides cardioprotection in the experimental model of myocardial
      ischemic reperfusion injury.
AB  - The present study was designed to evaluate the cardioprotective potential of
      pyruvate and to characterize the mechanism underlying the protection. Wistar
      albino rats were randomly divided into three groups. Two groups were administered
      saline orally (sham, ischemia-reperfusion (I-R) control group) and animals of
      third group received pyruvate (500 mg/kg) for 4 weeks. On the 29th day, animals
      of the I-R control and pyruvate treated groups underwent 45 min of occlusion of
      the left anterior descending (LAD) coronary artery and were thereafter reperfused
      for 60 min. In the I-R control group, a significant cardiac necrosis, depressed
      mean arterial pressure (MAP) and heart rate (HR), decline in myocardial
      antioxidant status and elevation in lipid peroxidation were observed as compared
      to sham control. Pyruvate treatment restored the myocardial antioxidant status
      and favorably modulated the altered MAP as compared to I-R control. Furthermore,
      I/R-induced lipid peroxidation was significantly inhibited by pyruvate treatment.
      These beneficial cardioprotective effects translated into significant improvement
      in MAP. Histopathological examination and restored specific myocardial injury
      marker CK-MB isoenzyme activity further confirmed protective effects of pyruvate.
      In conclusion, our study has demonstrated that the beneficial effect of pyruvate
      likely results from improved MAP and suppression of oxidative stress.

PMID- 16457856
TI  - Extremely low frequency magnetic field induces hyperalgesia in mice modulated by
      nitric oxide synthesis.
AB  - We investigated an effect of extremely low frequency magnetic field (ELF-MF, 60
      Hz) on hyperalgesia using hot plate test. The level of nitric oxide (NO) and the
      expression of nitric oxide synthase (NOS) were measured to determine if ELF-MF is
      engaged in NO mediated pain mechanism. Additionally, the involvement of Ca2+
      dependent NO pathway in ELF-MF induced hyperalgesia was evaluated by blocking
      Ca2+ sources with NMDA receptor antagonist and Ca2+ channel blocker. The exposure
      of mice to ELF-MF lowered pain threshold and elevated NO synthesis in brain and
      spinal cord. An NOS inhibitor blocked these effects of ELF-MF with attenuating
      the reduction of pain threshold and the rise of NO level in brain and spine by
      the exposure of ELF-MF. The hyperalgesic effects of ELF-MF were also blocked by a
      Ca2+ channel blocker, nimodipine, but not by a NMDA receptor antagonist, MK-801.
      The expression of Ca2+ -dependent nNOS and eNOS and Ca2+ -independent iNOS were
      not changed by ELF-MF. These results indicated that the exposure of ELF-MF might
      cause Ca2+ -dependent NOS activation, which then induces hyperalgesia with the
      increase in NO synthesis. In conclusion, ELF-MF may produce hyperalgesia by
      modulating NO synthesis via Ca2+ -dependent NOS.

PMID- 16457857
TI  - The new European Marine Strategy Directive: difficulties, opportunities, and
      challenges.

PMID- 16457859
TI  - Individual variability and photic entrainment of circadian rhythms in golden
      spiny mice.
AB  - Golden spiny mice are diurnally active in most of their natural habitat. Their
      diurnal activity is ascribed to non-photic cues: competitive exclusion from the
      nocturnal niche, or thermoregulatory considerations. Here we studied the
      entrainment of golden spiny mice to light. In the laboratory, golden spiny mice
      were primarily nocturnal and displayed an unusual variety of rhythm patterns,
      with activity bursts occurring during both activity and rest periods. Spontaneous
      shifts of activity rhythms between light phases were sometimes recorded. In all
      cases but one, body temperature shifted in parallel with activity. Under DD
      conditions, the free running period (tau) of all individuals but one was shorter
      than 24 h, and in all individuals but the same one it was shorter than tau under
      LL conditions. In response to a 6 h phase delay, all individuals entrained to the
      new LD cycle in a relatively uniform way. During phase advance four out of the
      twelve individuals further delayed their activity and body temperature rhythms,
      and eight individuals advanced their activity rhythm, but the re-entrainment took
      them over twice as long as to re-entrain to the phase delay. We suggest that the
      golden spiny mouse is a nocturnal rodent whose circadian system developed the
      flexibility to be nocturnal or diurnal according to environmental conditions, or
      a nocturnal rodent in the process of turning diurnal, and that it has low
      sensitivity to the immediate masking effect of light on activity.

PMID- 16457858
TI  - Genotoxic effects of bitumen fumes in Big Blue transgenic rat lung.
AB  - Road paving workers are exposed to bitumen fumes (CAS No. 8052-42-4), a complex
      mixture of volatile compounds and particles containing carcinogenic and non
      carcinogenic polycyclic aromatic hydrocarbons. However, epidemiological and
      experimental animal studies failed to draw unambiguous conclusions concerning
      their toxicity. In order to gain better insights on their genotoxic potential, we
      used an experimental design able to generate bitumen fumes at road paving
      temperature (temperature: 170 degrees C, total particulate matter: 100mg/m3) and
      perform a nose-only exposure of Big Blue transgenic rodents 6h/day for five
      consecutive days. The mutagenic properties of bitumen fumes were determined by
      analyzing the mutation frequency and spectrum of the neutral reporter gene cII
      inserted into the rodent genome. We previously observed in mouse lung, that
      bitumen fumes did not induce an increase of cII mutants, a modification of the
      mutation spectrum, nor the formation of DNA adducts. Since DNA adducts were found
      in the lungs of rats exposed to asphalt fumes in similar conditions, we decided
      to carry out an analogous experiment with Big Blue rats. A DNA adduct was
      detected 3 and 30 days after the end of treatment suggesting that these genetic
      alterations were quite steady. Thirty days after exposure, the cII mutant
      frequency was similar in control and exposed rats. In addition, a slight but not
      significant modification of the mutation spectrum associated with an increase of
      G:C to T:A and A:T to C:G transversions was noticeable in the treated animals.
      Then, these data failed to demonstrate a pulmonary mutagenic potential for
      bitumen fumes generated at road paving temperature in our experimental conditions
      despite the presence of a DNA adduct. These results may provide information
      concerning the pulmonary mechanism of action of this aerosol and may contribute
      to the occupational health hazard assessment.

PMID- 16457860
TI  - 1alpha,25(OH)2 vitamin D3 actions on ion channels in osteoblasts.
AB  - Membrane-initiated cellular responses to steroids include modulation of ion
      channel activities via signal transduction pathways. However, the molecular
      mechanisms involved in nongenomic actions remain only partially understood. Our
      research has focused on the rapid effects of 1alpha,25(OH)(2) Vitamin D(3)
      [1,25D] on L-type Ca(2+) [L-Ca] and DIDS-sensitive Cl(-) channels in osteoblasts.
      Physiological nanomolar concentrations of hormonally active 1,25D promote rapid
      (1-5 min) potentiation of outward Cl(-) currents in osteosarcoma ROS 17/2.8 cells
      and mouse primary osteoblasts. In addition, 1,25D increases inward barium
      currents through L-Ca channels at low depolarizing potentials within seconds in a
      fashion similar to the 1,4-dihydropyridine [DHP] agonist Bay K8644. We found that
      second messenger cAMP is involved in 1,25D potentiation of Cl(-) and Ca(2+)
      channels. Nongenomic 1,25D effects on ion channel activities in osteoblasts
      appear to involve different mechanisms that include a possible direct interaction
      with the L-Ca channel molecule, on one hand, and signaling through the cAMP
      pathway, on the other. Rapid 1,25D actions on Cl(-) and Ca(2+) currents seem to
      couple to secretory activities in osteoblasts, thus contributing to bone mass
      formation.

PMID- 16457861
TI  - CNS and anticonvulsant activity of a non-protein toxin (KC-MMTx) isolated from
      King Cobra (Ophiophagus hannah) venom.
AB  - In the present study, King Cobra (Ophiophagus hannah) venom was subjected to TLC
      followed by column chromatography/HPLC to isolate and purify a non-protein toxin
      designated as KC-MMTx. (1)H NMR, IR and EIMS studies showed KC-MMTx likely to be
      a 282 D unsaturated aliphatic acid having molecular formula C18H34O2. The minimum
      lethal dose of KC-MMTx was 200 microg/kg (i.v.) and 350 microg/kg (i.p.) in Swiss
      albino male mice. It significantly increased pentobarbitone induced sleeping time
      and significantly decreased the body temperature of male albino mice. It provided
      protection against amphetamine aggregate toxicity in mice but failed to protect
      amphetamine stereotypy in male albino rats. KC-MMTx provided significant
      protection against drug (strychnine, pentylenetetrazole, yohimbine) induced
      convulsions in male albino mice. It increased serum Na+ and decreased serum Ca2+
      significantly in male mice. MAO activity and brain neurotransmitter levels in
      male mice were altered significantly. Further detailed study is warranted on the
      CNS, anticonvulsant potential of KC-MMTx, which may lead to the development of
      newer therapeutic tools in the near future.

PMID- 16457862
TI  - Two novel O-superfamily conotoxins from Conus vexillum.
AB  - O-superfamily conotoxins include several families that have diverse
      pharmacological activity on Na+, K+ or Ca2+ channels. These superfamily toxins
      have been mainly found in fish-hunting and mollusk-hunting Conus species. Here,
      we reported two novel O-superfamily conotoxins, vx6a and vx6b, purified from a
      worm-hunting cone snail, Conus vexillum. Though their cysteine framework and
      signal peptides share high similarity with those of other members of O
      superfamily, the mature vx6a and vx6b both have a low sequence homology with
      others. To test the biological function of vx6a, the toxin was chemically
      synthesized and then tested on the locust dorsal unpaired median (DUM) neuron
      system which containing various ion channels. Although no any activity on ion
      channels was found on the DUM neuron system, vx6a could clearly elicit a series
      of symptoms in mouse via intracranial injection, such as quivering, climbing,
      scratching, barrel rolling and paralysis of limbs at different dose.

PMID- 16457863
TI  - Divergence of genes encoding B chains of beta-bungarotoxins.
AB  - The structural organization of the genes encoding B2, B4, B5 and B6 chains of
      beta-bungarotoxins are reported in this study. These genes shared virtually
      identical overall organization with three exons interrupted by two introns in
      similar positions. On the contrary, intron 1 of these genes had a similar size, a
      notable variation with the size of intron 2 was observed. It was found that two
      regions at the second intron of B1 and B2 chains were absent in that of B4, B5
      and B6 chains. RT-PCR analyses indicated that Bungarus multicinctus venom gland,
      heart, liver and muscle expressed the RNA transcripts showing sequence similarity
      with the intronic segment being deleted in B4, B5 and B6 chain genes. This
      reflects that the ancestral gene of the intronic segment might insert in multiple
      loci of B. multicinctus genome. Comparative analyses of B chain genes showed that
      the protein-coding regions of the exons are more diverse than introns, except for
      in the signal peptide domain. These results suggest that intron insertions or
      deletions occur with the evolution of B chains, and that accelerated evolution
      may diversify the protein-coding sequence of B chain genes same as snake
      phospholipase A2, neurotoxin and cardiotoxin genes.

PMID- 16457864
TI  - Damage of cell membrane and antioxidative system in human erythrocytes incubated
      with microcystin-LR in vitro.
AB  - The effect of the exposure of human erythrocytes to different concentrations of
      microcystin-LR were studied. Lipid peroxidation, membrane fluidity, cell
      morphology, haemoglobin oxidation and changes in the activity of antioxidant
      enzymes were investigated. Human erythrocytes were incubated with microcystin-LR
      at concentrations of 1-1000 nM for 1, 6, 12 and 24 h. We observed that
      microcystin-LR induces a significant increase of the level of thiobarbituric acid
      reactive substances (TBARS), formation of echinocytes, haemolysis, conversion of
      oxyhaemoglobin to methaemoglobin, decrease of membrane fluidity on the level of
      16 carbon atom fat acids. The compound also changed antioxidative enzymes
      activities: catalase, superoxide dismutase and glutathione reductase and
      formation of reactive oxygen species (ROS). All of the observed changes point out
      that 100 nM of Microcistin LR is the liminal (threshold) toxic dose for human
      erythrocytes. This dose caused most of the described changes. Observed damages of
      erythrocytes membrane and antioxidative enzymes may be the result of direct
      covalent binding of microcystin-LR with -SH residues of proteins and indirectly
      be related with reactive oxygen species formation.

PMID- 16457865
TI  - Aflatoxin M1 absorption and cytotoxicity on human intestinal in vitro model.
AB  - Aflatoxin M1 (AFM1) is the principal hydroxylated Aflatoxin B1 (AFB1) metabolite
      and is detected in milk of mammals, after consumption of feed contaminated with
      AFB1. As it is classified as probable human carcinogen (group 2B of the IARC),
      most countries have regulated its maximum allowed levels in milk in order to
      reduce AFM1 risk (50 ng/kg the EU and 500 ng/kg in the USA). It was demonstrated
      that if AFB1 must be converted into its reactive epoxide to exert its effects,
      and the protein binding may play an important role in its cytotoxicity.
      Conversely, the AFM1 epoxidation in human liver microsomes is very limited and
      studies with human cell line (MCL5), expressing or not expressing cytochrome P450
      enzymes, demonstrated a direct toxic potential of AFM1 in absence of metabolic
      activation. For this reason, while AFM1 is generally considered a detoxification
      product of AFB1 relatively to carcinogenicity and mutagenicity property, this is
      not always true for cytotoxicity activity. Aim of this work is to evaluate the
      intestinal absorption of AFM1 using a human in vitro model, the Caco-2 cell line.
      Either the parental Caco-2 cell line or its derived clone TC7, with higher
      metabolic competence, have been used. They were treated with different
      concentrations of AFM1, that mirror the milk contamination level (0.3-32 nM
      corresponding to 10-10,000 ng/kg), either in undifferentiated or in
      differentiated phase of growth. After 48 h of treatment in serum free medium, a
      dose dependent absorption of AFM1 has been detected in both cell lines,
      especially in differentiated cells, while, no appreciable effects on cell
      viability were observed, except for a general cellular suffering, revealed by LDH
      release, particularly evident in the undifferentiated cells. As well, no
      metabolites or AFM1 conjugates have been detected. The present results may be
      crucial for the evaluation of human risk to AFM1 exposure, in particular for
      children's population, due to their large use of milk and derivatives.

PMID- 16457866
TI  - Single-stranded DNA of Tomato leaf curl virus accumulates in the cytoplasm of
      phloem cells.
AB  - Geminiviruses have been reported to replicate in, and localize to, the nuclei of
      host plant cells. We have investigated the tissue and intracellular distribution
      of the monopartite Tomato leaf curl virus (TLCV) by in situ hybridization.
      Contrary to the current understanding of geminiviral localization, single
      stranded (ss) DNA of TLCV accumulated in the cytoplasm. TLCV ssDNA was also found
      in the nucleus, as was lower levels of replicative form double-stranded (ds) DNA.
      Under the same conditions, Tomato golden mosaic virus (TGMV) ssDNA and dsDNA were
      found in nuclei. ssDNA of TLCV, TGMV, and Tomato yellow leaf curl Sardinia virus
      (TYLCSV) was detected in some xylem vessels under specific hybridization
      conditions. Tissue specificity of TLCV was partially released by co-infection
      with TGMV. Our observations suggest that the mechanism of TLCV movement may
      differ from that of bipartite begomoviruses.

PMID- 16457867
TI  - Assembly of bacteriophage P2 and P4 procapsids with internal scaffolding protein.
AB  - Assembly of the E. coli bacteriophage P2 into an icosahedral capsid with T = 7
      symmetry is dependent on the gpN capsid protein, the gpQ connector protein and
      the gpO internal scaffolding protein. In the presence of the P4-encoded protein
      Sid, the same proteins are assembled into a smaller capsid with T = 4 symmetry.
      Although gpO has long been expected to act as an internal scaffolding protein, it
      has not been possible to produce P2 procapsids efficiently in vitro or in vivo
      due to a failure to express gpO at high levels. In this study, we find that full
      length gpO undergoes proteolytic degradation within 1 h of induction of
      expression. However, a truncated version of gpO lacking the N-terminal 25 amino
      acids (Odelta25) is stably expressed at high levels and is able to direct the
      formation of P2 size procapsids. In the presence of Sid, Odelta25 is incorporated
      into P4 procapsids, showing that Sid overrides the effect of gpO on capsid size
      determination.

PMID- 16457868
TI  - Analysis of HIV-2 Vpx by modeling and insertional mutagenesis.
AB  - Vpx facilitates HIV-2 nuclear localization by a poorly understood mechanism. We
      have compared Vpx to an NMR structure HIV-1 Vpr in a central helical domain and
      probed regions of Vpx by insertional mutagenesis. A predicted loop between
      helices two and three appears to be unique, overlapping with a known novel
      nuclear localization signal. Overall, Vpx was found to be surprisingly flexible,
      tolerating a series of large insertions. We found that insertion within the
      polyproline-containing C-terminus destabilizes nuclear localization, whereas
      mutating a second helix in the central domain disrupts viral packaging. Other
      insertional mutants in the predicted loop and in a linker region between the
      central domain and the C-terminus may be useful as sites of intramolecular tags
      as they could be packaged adequately and retained preintegration complex
      associated integration activity in a serum starvation assay. An unexpected result
      was found within a previously defined nuclear localization motif near aa 71. This
      mutant retained robust nuclear localization in a GFP fusion assay and was
      competent for preintegration complex associated nuclear import. In summary, we
      have modeled helical content in Vpx and assessed potential sites of
      intramolecular tags which may prove useful for protein-protein interactions
      studies.

PMID- 16457869
TI  - Complete nucleotide sequence and genome analysis of bacteriophage BFK20--a lytic
      phage of the industrial producer Brevibacterium flavum.
AB  - The entire double-stranded DNA genome of bacteriophage BFK20, a lytic phage of
      the Brevibacterium flavum CCM 251--industrial producer of L-lysine--was sequenced
      and analyzed. It consists of 42,968 base pairs with an overall molar G + C
      content of 56.2%. Fifty-five potential open reading frames were identified and
      annotated using various bioinformatics tools. Clusters of functionally related
      putative genes were defined (structural, lytic, replication and regulatory). To
      verify the annotation of structural proteins, they were resolved by 2D gel
      electrophoresis and were submitted to N-terminal amino acid sequencing.
      Structural proteins identified included the portal and major and minor tail
      proteins. Based on the overall genome sequence comparison, similarities with
      other known bacteriophage genomes include primarily bacteriophages from
      Mycobacterium spp. and some regions of Corynebacterium spp. genomes--possible
      prophages. Our results support the theory that phage genomes are mosaics with
      respect to each other.

PMID- 16457870
TI  - Detection of hepatitis A virus (HAV) in oysters (Crassostrea gigas).
AB  - Because shellfish (oysters, clams, and mussels) are filter-feeders, pathogens
      become concentrated within them, and human consumption of raw, or under-cooked
      shellfish can result in disease outbreaks. Identification of hepatitis A virus
      (HAV) in shellfish has been difficult for several reasons: the concentration of
      virions in shellfish tissues are very low, detection methods based on in vitro
      propagation are unreliable, recovery of virions from shellfish tissues is
      inefficient, and PCR inhibitors in shellfish tissues limit the success of RT-PCR.
      These facts underlie difficulties in determining cause and effect relationships
      between hepatitis A outbreaks and detection of HAV contamination in shellfish
      samples. We have developed a reliable and highly sensitive method for detection
      of HAV in oyster tissues at low levels (0.001 FFU/ml-fluorescent focus units per
      milliliter). Our method combines dissection of the gastrointestinal oyster tract,
      organic extraction before PEG precipitation, and RNA extraction with Trizol LS,
      followed by RT-PCR and hybridization using a digoxigenin-labeled HAV cDNA probe.
      Our results will benefit both public health officials concerned about hepatitis A
      infections caused by consumption of HAV-contaminated oysters and shellfish
      producers who require reliable methods for quality control of commercial oyster
      production.

PMID- 16457871
TI  - A Raman-active competitive inhibitor of OMP decarboxylase.
AB  - 6-Cyanouridine 5'-phosphate was shown to act as a competitive inhibitor of yeast
      OMP decarboxylase, with a K(i) value of 1.1 x 10(-5)M. Upon binding by the active
      site of yeast OMP decarboxylase (EC 4.1.1.23), the Raman stretching frequency of
      the nitrile group of 6-cyanouridine 5'-phosphate decreases from 2240 to 2225 cm(
      1). Based on the behavior of a model compound, 6-cyano-1,3-dimethyluracil, and on
      vibrational calculations, the observed change in stretching frequency is
      attributed to desolvation of the ligand, and distortion of the ligand in which
      the nitrile group moves out of the plane of the pyrimidine ring. Similar
      distortions may play a role in substrate activation by OMP decarboxylase,
      contributing to the catalytic process.

PMID- 16457872
TI  - Defining the toxic mode of action of ester sulphonates using the joint toxicity
      of mixtures.
AB  - Previously we have presented aquatic toxicity data for the class of anionic
      surfactant ester sulphonates (ES) to Daphnia magna. We now present toxicity data
      for binary mixtures of ES substances with reference substances of known mode of
      action. Using a toxic unit (TU) approach, data indicated that ES substances
      exhibit concentration addition with linear alkylbenzene sulphonate (LAS) and
      phenols and response addition with alcohols. This suggests that ES behave with a
      similar mode of action to phenol and LAS which are known polar narcotics and with
      a dissimilar mode of action to alcohols which are known baseline narcotics.

PMID- 16457873
TI  - Accumulation of mercury, selenium and their binding proteins in porcine kidney
      and liver from mercury-exposed areas with the investigation of their redox
      responses.
AB  - The subcellular localization of Se and Hg and their cytosolic binding proteins,
      including cellular oxidative status, in porcine liver and kidney have been
      studied by using samples from a chronic Hg-contaminated area and a non-Hg
      contaminated area. Coaccumulation and redistribution of Se and Hg in subcellular
      fractions due to mercury exposure were found. The Hg and Se concentrations in
      tissues from Hg-exposed porcine were 80 fold and 5-20 fold higher than controls,
      respectively. Interestingly, the retention of both Se and Hg increased 10% in
      mitochondria, while decreased 10% in cytosol of Hg-exposed pig liver. Mercury was
      mainly in the form of MTs in the cytosol of the non-Hg-exposed porcine kidney. MT
      binds Hg in the cytosol with limited capacity, and the rest Hg was redistributed
      to the high molecular weight (MW) proteins (80-100 kDa) in the Hg-exposed group.
      The coaccumulation of Hg and Se was also found in high MW proteins, where their
      molar ratio tended to be 1:1. Moreover, the Se-containing polypeptides (3-6 kDa)
      increased significantly both in hepatic and renal cytosol of the Hg-exposed pigs.
      Se-dependent GSH-Px and SOD activity were increased to cope with Hg-induced
      oxidative stress. In previous studies, the roles of Se and MTs were generally
      taken into account separately; we discussed their combining roles in the case of
      high Hg exposure. The present results were beneficial to understand the existing
      states of Hg in vivo and evaluate the interaction of toxic and essential
      elements.

PMID- 16457874
TI  - False positive results in chimeraplasty for von Willebrand Disease.
AB  - Chimeraplasty or the use of chimeric RNA/DNA oligonucleotides (RDOs) to correct
      single-base mutations emerged in the field of gene therapy with reported base
      pair conversions of up to 40%. We investigated the applicability of chimeraplasty
      to correct a point mutation in the von Willebrand Factor (VWF) gene resulting in
      a von Willebrand Disease (VWD) type 3 phenotype. Although we have access to VWD
      type 3 dogs, we used wild type endothelial cells for in vitro studies, as
      isolation of endothelial cells from VWD type 3 dogs is not straightforward due to
      the bleeding diathesis. RDOs to convert the wild type VWF gene into VWD type 3
      gDNA were constructed and used in various transfection conditions. However, no
      gene conversion could be detected either in the RNA or in the DNA isolated from
      transfected cells, not even with the sensitive colony hybridisation technique,
      despite the presence of RDOs in the cell nucleus. On the other hand, sequence
      analysis of isolated DNA of transfected cells did reveal the presence of VWF type
      3 DNA. However, this apparent conversion is very likely not the result of RDO
      mediated nucleotide conversion as the same VWF type 3 DNA sequence was also
      detected in negative control experiments where no RDO was used. Our negative
      results are in line with the emerging reports of chimeraplasty failure and can
      contribute to the call for an international "chimeraplasty consortium" with free
      exchange of results to clarify the controversy about the applicability of the RDO
      mediated base conversion.

PMID- 16457875
TI  - Epigenetic regulation of maspin expression in human ovarian carcinoma cells.
AB  - OBJECTIVE: Maspin expression is often deregulated in human cancer cells compared
      to their normal cells due to loss of epigenetic control. In contrast to normal
      human ovarian surface epithelial (HOSE) cells, ovarian carcinoma cells display a
      gain of maspin mRNA expression. The objective of this study was to determine
      whether gain of maspin expression in ovarian cancer is governed by epigenetic
      mechanisms. METHODS: We examined the cytosine methylation and chromatin
      accessibility status of the maspin promoter in normal HOSE cells and ovarian
      carcinoma cells with real-time RT-PCR, sodium bisulfite genomic sequencing, and
      chromatin accessibility assays. 5-Aza-2'-deoxycytidine (5-aza-dC) was used to
      induce demethylation of the maspin promoter. Ad p53 was used to induce transient
      overexpression of wild-type p53. RESULTS: Normal HOSE cells were maspin-negative
      in association with methylation of the maspin promoter. In the maspin-positive
      ovarian cancer cell lines, the maspin promoter was unmethylated. Increased maspin
      expression in ovarian carcinoma cells was accompanied by a more accessible
      chromatin structure in the maspin promoter. In the maspin-negative ovarian cancer
      cell line A222, maspin could be induced following 5-aza-dC treatment or by forced
      overexpression of p53. CONCLUSIONS: These results suggest that changes in
      cytosine methylation and chromatin accessibility play an important role in maspin
      expression in human ovarian carcinoma. Deregulation of maspin expression in
      ovarian cancer is due to loss of epigenetic control as has been shown in other
      cancers. This observation provides further evidence of the strict epigenetic
      control of the maspin gene.

PMID- 16457876
TI  - Effectiveness of postoperative chemotherapy for para-aortic lymph node metastasis
      of endometrial cancer.
AB  - OBJECTIVE: To examine the effectiveness of postoperative chemotherapy for para
      aortic lymph node (PAN) metastasis in patients with endometrial cancer. METHODS:
      Among 350 clinical stage I-II endometrial cancer patients who underwent systemic
      pelvic and para-aortic lymphadenectomy during the period 1995 through 2002, 26
      patients were identified with PAN metastasis. Of these patients, nine had only
      one positive PAN and 17 had two or more positive PANs (mean 4.9, range 1-22). All
      patients were treated postoperatively with a single chemotherapy regimen
      consisting of ifosfamide, epiadriamycin, and cisplatin scheduled for 5 cycles.
      Median (range) follow-up for surviving patients was 85 (38-119) months. Treatment
      outcome, including disease-free survival relative to the number of positive PANs,
      was investigated. RESULTS: Among the 26 patients with PAN involvement, four
      developed recurrence. Three of the four patients had 10 or more positive PANs.
      Estimated 5-year disease-free survival rates were 89% for patients with one
      positive PAN, 82% for those with two or more positive PANs, and 85% for all
      patients. No significant difference was identified between the first two groups
      (P = 0.6543). CONCLUSIONS: Postoperative chemotherapy can yield a favorable
      outcome in endometrial cancer patients with PAN metastasis, even those with
      multiple positive nodes.

PMID- 16457878
TI  - Collagen scaffolds derived from a marine source and their biocompatibility.
AB  - The primary sources of industrial collagens are calf skin and bone. However,
      these carry a high risk of bovine spongiform encephalopathy or transmissible
      spongiform encephalopathy. In this study, a novel form of acid-soluble collagen
      was extracted from jellyfish in an effort to obtain an alternative and safer
      collagen. Porous scaffolds composed of jellyfish collagen were prepared by freeze
      drying and cross-linking with 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide
      hydrochloride/N-hydroxysuccinimide to be used in tissue engineering applications.
      Enzymatic degradation kinetics of jellyfish collagen scaffolds were controlled by
      EDC/NHS-cross-linking density. Results from an MTT assay indicated that jellyfish
      collagen exhibited higher cell viability than other naturally derived
      biomaterials, including bovine collagen, gelatin, hyaluronic acid, and glucan.
      Jellyfish collagen scaffolds also had a highly porous and interconnected pore
      structure, which is useful for an high-density cell seeding, an efficient
      nutrient and an oxygen supply to the cells cultured in the three-dimensional
      matrices. To determine whether jellyfish collagen evokes any specific
      inflammatory response compared to that induced by bovine collagen or gelatin, we
      measured the levels of pro-inflammatory cytokines and antibody secretions and
      monitored the population changes of immune cells after in vivo implantation.
      Jellyfish collagen was found to induce an immune response at least comparable to
      those caused by bovine collagen and gelatin.

PMID- 16457879
TI  - Evaluation of silicon nanoporous membranes and ECM-based microenvironments on
      neurosecretory cells.
AB  - Understanding the interactions between microfabricated synthetic interfaces and
      cultured cells expressing a neuronal phenotype are critical for advancing
      research in the field of neural engineering such as neural recording and
      stimulation and neural microdevice interactions with the human brain. Here we
      explore the integration of these two components for therapeutic applications of
      neural prostheses. Microfabricated silicon nanoporous membranes were investigated
      for their effects on survival, proliferation, and differentiation of the well
      known PC12 clonal line. Specifically, cell morphology, examined through
      fluorescence staining, were comparable in many respects on both silicon membrane
      and widely-used polystyrene culture surfaces. The attachment and differentiation
      of PC12 cells cultured on collagen and laminin-modified membranes and standard
      tissue culture surfaces were similar. Lastly, the differentiation response and
      tyrosine hydroxylase activity of PC12 cells embedded in a type I collagen matrix
      on experimental membrane substrates while exposed to NGF were significant and
      indistinguishable from tissue-culture polystyrene (TC-PS) surfaces. Results from
      this research suggest that microfabricated silicon nanoporous membranes may be
      useful, biocompatible permselective structures for neuroprosthetic applications
      and that collagen may be a useful immobilizing matrix for PC12 cells loaded in
      implantable macroencapsulation devices designed for the treatment of
      neurodegenerative disorders.

PMID- 16457880
TI  - Characterizing the modification of surface proteins with poly(ethylene glycol) to
      interrupt platelet adhesion.
AB  - Surface protein modification with poly(ethylene glycol) (PEG) can inhibit acute
      thrombosis on damaged vascular and biomaterial surfaces by blocking surface
      protein-platelet interactions. However, the feasibility of employing protein
      reactive PEGs to limit intravascular and biomaterial thrombosis in vivo is
      contingent upon rapid and extensive surface protein modification. To characterize
      the factors controlling this potential therapeutic approach, the model protein
      bovine serum albumin was adsorbed onto polyurethane surfaces and modified with
      PEG-carboxymethyl succinimidyl ester (PEG-NHS), PEG-isocyanate (PEG-ISO), or PEG
      diisocyanate (PEG-DISO) in aqueous buffer at varying concentrations and contact
      times. It was found that up to 5 PEGs could be attached per albumin molecule
      within one min and that adsorbed albumin PEGylation approached maximal levels by
      6min. The lability of reactive PEGs in aqueous buffer reduced total protein
      modification by 50% when the PEG solution was incubated for 7min prior to
      application. For fibrinogen PEGylation (performed in the solution phase), PEG-NHS
      was more reactive than PEG-ISO or PEG-DISO. The gamma peptide of fibrinogen,
      which contains several key platelet-binding motifs, was highly modified. A marked
      reduction in platelet adhesion was observed on fibrinogen-adsorbed polyurethane
      treated with PEG-NHS or PEG-DISO. Relative differences in platelet adhesion on
      PEG-NHS and PEG-DISO modified surfaces could be attributed to differences in
      reactivity towards fibrinogen and the size of the polymer backbone. Taken
      together, these findings provide insight and guidance for applying protein
      reactive PEGs for the interruption of acute thrombotic deposition.

PMID- 16457881
TI  - Fragment size- and dose-specific effects of hyaluronan on matrix synthesis by
      vascular smooth muscle cells.
AB  - Tissue engineering of vascular elastin matrices disrupted by mechanical injury,
      disease, or congenitally absent, is among other factors, limited by the lack of
      suitable cell scaffolds to up-regulate and guide innately poor elastin synthesis
      by adult vascular smooth muscle cells (SMCs). Evidence suggests that scaffolds
      based on hyaluronan (HA), a glycosaminoglycan, may be useful to elicit
      elastogenic cell responses, although these effects appear to be dictated by HA
      fragment size and/or dose. This study investigates the efficacy of a simple,
      frequently adopted exogenous HA supplementation model to test this hypothesis.
      Rat aortic SMCs were cultured with HA (2 x 10(6) Da (HMW) > or = MW < or = 2.2 x
      10(4) Da) supplemented at doses between 0.2 and 200 microg/ml. Cell layers were
      biochemically assayed for DNA, elastin and collagen content. Fragmented, but not
      high molecular weight (HMW) HA, stimulated cell proliferation in inverse
      correlation fragment size while the opposite effect was observed for synthesis of
      soluble and matrix elastin; almost no dose effects were observed within any
      group. SDS-Page/Western Blot and a desmosine assay semi-quantitatively confirmed
      the observed biochemical trends for tropoelastin and matrix elastin,
      respectively. Quantitative differences in elastin deposition were mirrored in TEM
      micrographs. Elastin was mostly deposited in the form of amorphous clumps but
      fibers were increasingly present in cell layers cultured with HMW HA. HA and its
      fragments did not disrupt normal fibrillin-mediated mechanisms of elastin matrix
      deposition. While the current outcomes confirm that the effects of HA on elastin
      synthesis are fragment size-specific, this study shows that an exogenous
      supplementation model does not necessarily simulate cellular matrix synthesis
      responses to HA-based biomaterial scaffolds.

PMID- 16457882
TI  - Combination of baculovirus-mediated gene transfer and rotating-shaft bioreactor
      for cartilage tissue engineering.
AB  - We have previously demonstrated efficient baculovirus transduction of rat
      chondrocytes in 6-well plates. To further explore the potential of baculovirus in
      cartilage tissue engineering, the baculovirus-transduced chondrocytes were seeded
      into porous scaffolds and cultivated in a rotating-shaft bioreactor (RSB) which
      was developed for two-phase cultivation of tissue engineered cartilage. The
      baculovirus transduction resulted in efficiencies up to 90%, and affected neither
      cell adhesion to the scaffolds nor cell survival in the RSB. After 4-week RSB
      cultivation, the transduced cells remained highly differentiated and grew into
      constructs that resembled the untransduced constructs with regard to gross
      appearance, construct size, cell morphology, cell spatial distribution,
      glycosaminoglycan and collagen production and deposition. Importantly,
      baculovirus transduction did not alter the expression of chondrocytic genes.
      These data confirmed that baculovirus transduction neither harms chondrocytes nor
      retards the formation of cartilage-like tissues in the RSB, thus implicating the
      potentials of combining baculovirus-mediated gene transfer with RSB cultivation
      in in vitro cartilage tissue engineering.

PMID- 16457883
TI  - UHMWPE and vitamin E bioactivity: an emerging perspective.
AB  - Ultra-high molecular weight polyethylene (UHMWPE) is a semicrystalline
      biomaterial widely used in the components for articular prosthesis for its
      excellent mechanical qualities. Two major problems limit the UHMWPE prosthesis
      life-wearing and delamination, both phenomena being mainly due to chemical
      oxidation of polymer. Wearing causes the release of generated particulate that
      triggers a macrophage reaction leading to chronic inflammation and osteolysis,
      while delamination, due to the mechanical stress, macroscopically alters the
      surfaces. The most diffused method to reduce wearing is UHMWPE molecular cross
      linking by high-energy irradiation followed by melting that also reduces polymer
      fatigue strength. For this reason, the use of vitamin E (alpha-tocopherol), as an
      anti-oxidative and biocompatible additive for normal and cross-linked UHMWPE, has
      been suggested as an alternative method to improve polymer wearing resistance
      without altering its mechanical strength. This paper describes briefly the
      rationale of vitamin E as UHMWPE additive and its possible use as an emerging
      perspective in the orthopaedic field.

PMID- 16457884
TI  - Expression of the myeloperoxidase gene in AC133 positive leukemia cells relates
      to the prognosis of acute myeloid leukemia.
AB  - We previously reported that the percentage of myeloperoxidase (MPO) positive
      blasts had a prognostic impact on survival of patients with acute myeloid
      leukemia (AML). To extend this observation, we quantitatively measured the level
      of the MPO gene in AC133 positive leukemia cells that would contain a putative
      AML stem/progenitor compartment. AML cases were divided into the MPO gene high
      (MPOg-H) and MPO gene low (MPOg-L) groups. Only patients belonging to the MPOg-H
      group had a favorable chromosomal translocation, t(8;21), and having no
      morphological dysplasia that was associated with MPOg-L. The difference in the
      survival of MPOg-H and MPOg-L was statistically meaningful, demonstrating the
      possible prognostic impact of the expression of MPO gene in AC133 positive
      leukemia cells.

PMID- 16457885
TI  - HIV-1 protease inhibitor ritonavir potentiates the effect of 1,25
      dihydroxyvitamin D3 to induce growth arrest and differentiation of human myeloid
      leukemia cells via down-regulation of CYP24.
AB  - HIV-1 protease inhibitor, ritonavir (RTV) is a potent inhibitor of cytochrome
      p450 (CYPs) enzymes. This study explored the effects of RTV on CYP24 which
      converts 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] to its inactive form
      1,24,25,(OH)(3). Real-time RT-PCR showed that exposure of HL-60 cells to
      1,25(OH)(2)D(3) induced expression of CYP24, and pre-incubation of these cells
      with RTV decreased this transcripts, resulting in increased intracellular levels
      of 1,25(OH)(2)D(3) and potentiation of the ability of 1,25(OH)(2)D(3) to induce
      growth arrest and differentiation of these cells. Taken together, inhibition of
      CYP24 might open a new paradigm for therapy using Vitamin D compounds.

PMID- 16457886
TI  - The neurocognitive bases of human multimodal food perception: sensory
      integration.
AB  - This review addresses a fundamental neuroscientific question in food perception:
      how multimodal features of food are integrated. Much research and
      conceptualization has emerged related to multisensory integration in vision,
      audition and somatosensation, while it remains poorly understood and researched
      within the chemical and mouth feel senses. This review aims to bridge this gap.
      We discuss the main concepts in the fields of auditory, visual and somatosensory
      multisensory integration and relate them to oral-sensory (gustatory and
      somatosensory) and olfactory (orolfactory) interactions. We systematically review
      the psychophysical literature pertaining to intra- and intermodal interactions
      related to food perception, while making explicit distinctions between peripheral
      and central interactions. As the neural bases of crossmodal orolfaction currently
      are poorly understood, we introduce several plausible neuroscientific models,
      which provide a framework for further neuroscientific exploration in this area.
      We are guided by a new meta-analysis of the odor-taste neuroimaging literature,
      as well as by single-unit, anatomical and psychophysical studies. Finally, we
      propose strong involvement of recurrent neural networks in multisensory
      integration and make suggestions for future research.

PMID- 16457887
TI  - Functional neuroimaging findings on the human perception of illusory contours.
AB  - Illusory contours (IC) have attracted a considerable interest in recent years to
      derive models of how sensory information is processed and integrated within the
      visual system. In addition to various findings from neuropsychology,
      neurophysiology, and psychophysics, several recent studies have used functional
      neuroimaging to identify the cerebral substrates underlying human perception of
      IC (in particular Kanizsa figures). In this paper, we review the results from
      more than 20 neuroimaging studies on IC perception and highlight the great
      diversity of findings across these studies. We then provide a detailed discussion
      about the localization ('where' debate) and the timing ('when' debate) of IC
      processing as suggested by functional neuroimaging. Cortical responses involving
      visual areas as early as V1/V2 and latencies as rapid as 100 ms have been
      reported in several studies. Particular issues concerning the role of the right
      hemisphere and the retinotopic encoding of IC are also discussed. These different
      findings are tentatively brought together to propose different hypothetical
      cortical mechanisms that might be responsible for the visual formation of IC.
      Several remaining questions on IC processing that could potentially be explored
      with functional neuroimaging techniques are finally emphasized.

PMID- 16457888
TI  - Determination of toluene in brain of freely moving mice using solid-phase
      microextraction technique.
AB  - For the purpose of measuring the pharmacokinetics of inhaled toluene in the brain
      of mice, we developed a method for the direct detection of toluene by gas
      chromatography/mass spectrometry (GC/MS). The method uses a solid-phase
      microextraction (SPME) fiber inserted into the mouse' hippocampus (CA1) through a
      cannula fixed onto the animal. BALB/c mice were exposed to 0, 0.9, 9, 50 and 90
      ppm toluene for 30 min. The toluene level detected near the hippocampus by this
      method after exposure to 0.9 ppm toluene in air showed no significant difference
      from the level found in the non-exposure control group; however, the toluene
      level increased significantly after exposure to concentrations of 9, 50 and 90
      ppm. These increases were concentration-dependent. In addition, the
      pharmacokinetics of toluene in the brain of mice exposed to 50 ppm toluene showed
      that the toluene level decreased rapidly after the exposure, and returned to
      control levels after 60 min. This study describes the method which has
      successfully detected toluene levels in the brain of conscious, free-moving mice
      for the first time.

PMID- 16457889
TI  - Parkinsonism due to manganism in a welder: neurological and neuropsychological
      sequelae.
AB  - A 33-year-old welder with 3 years of exposure to manganese (Mn) bearing welding
      fumes was seen by neurologists for cognitive and motor complaints. He exhibited
      signs and symptoms of Parkinson's disease, including tremor, bradykinesia, gait
      disturbance and cogwheel rigidity. However, he was young and had significant
      inattention and forgetfulness, had found levodopa unhelpful and moved with a cock
      walk gait, all of which suggested manganism. His serum and urine levels of Mn
      were, in fact, elevated, and his brain MRI had increased T1-weighted signal
      intensities in the basal ganglia bilaterally (globus pallidus) consistent with Mn
      deposition. Two years later, he underwent comprehensive neuropsychological
      testing. Clinical history indicated a mild tremor and emotional dysfunction with
      irritability, anxiety, and depression with psychotic features. He showed deficits
      in cognitive flexibility, information processing and speed, and greatly reduced
      motor speed, which are consistent with a fronto-subcortical process. These
      findings support a diagnosis of early onset parkinsonism from welding.

PMID- 16457890
TI  - Synthesis, characterization and DNA-binding of novel chiral complexes delta- and
      lambda-[Ru(bpy)2L]2+ (L = o-mopip and p-mopip).
AB  - Novel chiral Ru(II) complexes [Ru(bpy)2L]2+ (bpy = 2,2-bipyridine; L: o-mopip = 2
      (2-methoxylphenyl)imidazo[4,5-f][1,10]phenanthroline, p-mopip = 2-(4
      methoxylphenyl)imidazo[4,5-f][1,10]phenanthroline) containing -OCH3 at different
      positions on the phenyl ring have been synthesized and characterized. The DNA
      binding and DNA-photocleavage properties of the complexes were investigated. The
      theoretical calculations for these complexes were also carried out applying the
      density functional theory (DFT) method. The experimental results show that: both
      these two isomer complexes can bind to DNA in an intercalative mode; the DNA
      binding affinity of [Ru(bpy)2(p-mopip)] 2 is greater than that of [Ru(bpy)2(o
      mopip)] 1; moreover, the DNA-binding affinities of enantiomers delta-1 and delta
      2 are all greater than those of lambda-1 and lambda-2, respectively. In addition,
      a very interesting finding is experimentally obtained, i.e. under a low
      [DNA]/[Ru] ratio, the emission intensities of delta-1 and lambda-1 are all weaker
      than those of delta-2 and lambda-2, however, upon a high [DNA]/[Ru] ratio, the
      emission intensities of both delta-1 and lambda-1 are stronger than those of
      delta-2 and lambda-2. Such a difference of the emission spectra can be
      interpreted by the electric effect of substituent on the intercalative ligand.
      The difference in DNA-binding affinities of these two isomeric complexes can also
      be reasonably explained by the DFT calculations.

PMID- 16457891
TI  - Spontaneous bilateral bacterial empyema in a patient with nephrotic syndrome.
AB  - Spontaneous bacterial empyema (SBEM), a rare infectious complication among liver
      cirrhosis patients, is characterized by infection in the presence of pleural
      effusion without evidence of pre-existing pneumonia. The prevalence of SBEM in
      cirrhotic patients with hydrothorax is about 13%. However, it has previously not
      been reported in medical literature in patients with nephrotic syndrome. The most
      common microorganism identified is Escherichia coli, followed by Streptococcus
      species, Enterococcus species, Klebsiella pneumoniae, and Pseudomonas stutzeri.
      We present a patient with a history of nephrotic syndrome caused by membranous
      nephropathy, who received steroids and cyclophosphamide. He developed bilateral
      SBEM due to Aeromonas hydrophila and E. coli, which were isolated from the left-
      and right-side pleural fluid, respectively. The detailed clinical course,
      treatment, and outcome are described.

PMID- 16457892
TI  - Cardiovascular endothelins: essential regulators of cardiovascular homeostasis.
AB  - The endothelin (ET) system consists of 3 ET isopeptides, several isoforms of
      activating peptidases, and 2 G-protein-coupled receptors, ETA and ETB, that are
      linked to multiple signaling pathways. In the cardiovascular system, the
      components of the ET family are expressed in several tissues, notably the
      vascular endothelium, smooth muscle cells, and cardiomyocytes. There is general
      agreement that ETs play important physiological roles in the regulation of normal
      cardiovascular function, and excessive generation of ET isopeptides has been
      linked to major cardiovascular pathologies, including hypertension and heart
      failure. However, several recent clinical trials with ET receptor antagonists
      were disappointing. In the present review, the authors take the stance that ETs
      are mainly and foremost essential regulators of cardiovascular function, hence
      that antagonizing normal ET actions, even in patients, will potentially do more
      harm than good. To support this notion, we describe the predominant roles of ETs
      in blood vessels, which are (indirect) vasodilatation and ET clearance from
      plasma and interstitial spaces, against the background of the subcellular
      mechanisms mediating these effects. Furthermore, important roles of ETs in
      regulating and adapting heart functions to different needs are addressed,
      including recent progress in understanding the effects of ETs on diastolic
      function, adaptations to changes in preload, and the interactions between
      endocardial-derived ET-1 and myocardial pump function. Finally, the potential
      dangers (and gains) resulting from the suppression of excessive generation or
      activity of ETs occurring in some cardiovascular pathological states, such as
      hypertension, myocardial ischemia, and heart failure, are discussed.

PMID- 16457893
TI  - Kinetic analysis of beta-amyloid peptide aggregation induced by metal ions based
      on surface plasmon resonance biosensing.
AB  - Recent studies suggest that beta-amyloid (Abeta) aggregation and toxicity are
      facilitated by metal ions. This study aims to evaluate the kinetics of Abeta
      aggregation/dissociation in the presence of metal ions and to investigate the
      efficacy of a metal chelator to disrupt the metal ion-induced Abeta aggregates.
      Soluble Abeta(1-40) peptide was immobilized on a surface plasmon resonance
      biosensing surface and aggregation induced by contact with soluble Abeta with or
      without metal ions. Our study revealed that all the tested metal ions promoted
      Abeta aggregation but with different kinetics. Among them, Cu(II) ions had the
      highest association constant, and reached the maximum binding in 10 min. However,
      the Cu(II)-induced Abeta aggregates were unstable. Other ions attained the
      maximum Abeta binding at much longer times: 45 min for Ca(II), 60 min for Fe(II),
      Fe(III), and Zn(II) ions. The Abeta aggregates induced by Fe(III) ions had the
      greatest stability. The metal ion-induced Abeta(1-40) aggregates could be
      disrupted by the metal chelator, EDTA, suggesting a metal chelator may serve as a
      pharmacological agent to interfere with Abeta aggregation. Finally, this study
      demonstrates that the SPR biosensor can be an effective and efficient setup to
      investigate the mechanism of Abeta aggregation.

PMID- 16457894
TI  - Enrolling research subjects from clinical practice: ethical and procedural issues
      in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.
AB  - The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is a
      multi-site effectiveness study funded by the National Institute of Mental Health
      (NIMH) with the aim of identifying successful, acceptable and cost-effective
      treatment strategies for outpatients with unremitted depression. With enrollment
      of 4,041 adults with major depressive disorder (MDD), it is the largest
      controlled psychiatric treatment study ever undertaken. In the course of
      developing procedures to ensure that ambitious enrollment goals were met, a
      number of ethical and practical issues became apparent that underscore the
      conflicts between effectiveness research and human subject protections. These are
      delineated as they relate to study design; eligibility criteria; incentives to
      subjects; investigators and clinical sites; the complementary roles of clinical
      research coordinators (CRCs) and study clinicians; and recruitment and consent
      procedures. The STAR*D trial exemplifies the interplay and tension between those
      strategies that integrate research and clinical aims and roles in the service of
      enhancing external validity, site participation, and recruitment and retention
      versus those strategies that differentiate research and clinical treatment in the
      service of research integrity and human subject protections. We hope that a
      discussion of these key challenges and dilemmas and how they have been addressed
      will help inform future discussions concerning design and conduct of ethical
      effectiveness trials designed to optimize care in real world clinical settings.

PMID- 16457895
TI  - Th2 cytokine response in Major Depressive Disorder patients before treatment.
AB  - In Major Depressive Disorder (MDD), the neuroendocrine and immune systems
      interactions are impaired. We investigated the pro/anti-inflammatory Th1/Th2
      cytokine balance in MDD patients and in non-depressed control group. The MDD
      subjects showed higher levels of cortisol and TNF-alpha, increased CD3+CD8+ and
      NK percentages, diminished B cell counts and no significant variations in
      CD3+CD4+ lymphocyte. Moreover, higher levels of IL-4 and IL-13 (Th2) and
      significantly lower measurements of IL-2 and IFN-gamma (Th1) cytokines were also
      observed in the MDD group. Overall, we propose that all these changes could be
      related to the elevated cortisol levels seen in the MDD patients. Further studies
      are necessary to explore these findings and its implication in future therapeutic
      approach of MDD patients.

PMID- 16457896
TI  - Specific changes in hippocampal spatial codes predict spatial working memory
      performance.
AB  - This study examined the relationship between hippocampal place fields and spatial
      working memory. Place cells were recorded while rats solved a spatial working
      memory task in light and dark testing conditions. Rats made significantly more
      errors when tested in darkness, and although place fields changed in multiple
      ways in darkness, only changes in place field specificity predicted the degree of
      impaired spatial memory. This finding suggests that more spatially distinct place
      fields may contribute to hippocampal-dependent mnemonic functions.

PMID- 16457897
TI  - Hip fractures, nocturia, and nocturnal polyuria in the elderly.
AB  - This study was undertaken to evaluate the relation between hip fractures and
      nocturnal micturition habits in elderly men and women. A questionnaire survey was
      undertaken among 10,216 elderly subjects. The mean (+/-S.D.) ages of the men and
      women were 73.0+/-6.0 and 72.6+/-6.7 years, respectively. A hip fracture during
      the past five years had occurred in 97 (3.9%) of the men and 175 (4.6%) of the
      women and the occurrence increased with increasing age in both sexes. In both men
      and women nocturnal micturition increased with age. Among men, passing of
      subjectively large amounts of urine at night was reported to occur never or very
      seldom in 63.3% and rather seldom, rather often, and very often in 21.9%, 12.7%,
      and 2.1%, respectively. The corresponding frequencies in women were 65.1%, 17.2%,
      13.7%, and 3.9%, respectively. Multiple logistic regression analysis with sex,
      nocturia, and nocturnal voided volumes as independent variables and occurrence of
      hip fracture during the last five years as the dependent variable showed that the
      risk of having had a hip fracture was increased by nocturia three or more
      episodes versus two or fewer; odds ratio (OR) 1.8, confidence interval (CI) 1.1
      3.0, and by large nocturnal urine volumes, very often versus very seldom or
      never; (OR 3.5; CI 1.8-7.3). One can conclude that in these elderly subjects the
      risk of hip fractures during a five-year period was increased independently by
      increased nocturnal micturition and increased nocturnal urine output.

PMID- 16457898
TI  - Genomic flank-sequencing of plasposon insertion sites for rapid identification of
      functional genes.
AB  - Plasposons are modified mini-Tn5 transposons for random mutagenesis of Gram
      negative bacteria. Their unique design allows for the rescue cloning and
      sequencing of DNA that flanks insertion sites in plasposon mutants. However, this
      process can be laborious and time-consuming, as it involves genomic DNA
      isolation, restriction endonuclease treatment, subsequent religation,
      transformation of religated DNA into an Escherichia coli host, and re-isolation
      as a plasmid, which is then used as a template in sequencing reactions with
      primers that read from the plasposon ends into the flanking DNA regions. We
      describe here a method that produces flanking DNA sequences directly from genomic
      DNA that is isolated from plasposon mutants. By eliminating the need for rescue
      cloning, our protocol dramatically reduces time and effort, typically by 2 to 3
      working days, as well as costs associated with digestion, ligation,
      transformation, and plasmid isolation. Furthermore, it allows for a high
      throughput automated approach to analysis of the plasposome, i.e. the collective
      set of plasposon insertion sites in a plasposon mutant library. We have tested
      the utility of genomic flank-sequencing on three plasposon mutants of the soil
      bacterium Collimonas fungivorans with abolished ability to degrade chitin.

PMID- 16457899
TI  - Production, characterisation and potential application of a novel monoclonal
      antibody for rapid identification of virulent Listeria monocytogenes.
AB  - A panel of hybridomas was produced using intact Listeria monocytogenes serotype
      1/2a cells as the immunogen. An IgG2a monoclonal antibody (mAb) 'mAb2B3' was
      isolated that reacted with L. monocytogenes but not with a representative panel
      of related Listeria spp. and non-Listeria spp. Binding activity was greatest
      against L. monocytogenes serotype 1/2a and was significantly enhanced when cells
      were prepared in Listeria enrichment broth (LEB). The reactive epitope was
      deduced, by immunoblot analysis, to be a surface localised protein of
      approximately 80 kilodaltons (kDa), putatively assumed to be internalin A (InlA).
      Recombinant InlA protein was subsequently expressed in Escherischia coli. When
      crude E. coli cell lysates were subjected to immunoblot analysis, it was
      demonstrated that the mAb bound specifically to the heterologously expressed
      recombinant InlA protein, thus confirming the specificity of the mAb. The mAb was
      further evaluated in a series of enzyme-linked-immunosorbent assay (ELISA)-based
      formats and in a surface plasmon resonance (SPR)-based biosensor platform. Both
      configurations were capable of differential identification of virulent L.
      monocytogenes at concentrations greater than or equal to 1x10(7) cells/ml.
      Notwithstanding the apparent insensitivity, the results indicate that InlA could
      be exploited as a marker for highly specific confirmatory identification of
      pathogenic L. monocytogenes following primary enrichment of suspect food samples,
      using the anti-InlA antibody 'mAb2B3', described herein.

PMID- 16457900
TI  - Comparison of culture and biochemical tests with PCR for detection of Brachyspira
      hyodysenteriae and Brachyspira pilosicoli.
AB  - Traditional culture and biochemical tests (CBT) were compared with PCR for
      sensitivity and detection of Brachyspira hyodysenteriae and Brachyspira
      pilosicoli in seeded faeces and clinical samples from diarrhoeic pigs. A duplex
      PCR system was developed based on primers detecting the tlyA-gene of B.
      hyodysenteriae and the 16S rRNA-gene of B. pilosicoli. Sensitivities for the PCR
      system were determined on seeded faeces, using DNA that had been recovered from
      primary cultures or extracted directly from faeces. Compared to CBT, PCR applied
      to DNA extracted directly from faeces lowered the sensitivity by a factor of 1000
      to 10,000. B. hyodysenteriae and B. pilosicoli detection was compared for CBT and
      PCR using 200 clinical samples. CBT detected more B. hyodysenteriae isolates in
      the clinical samples than PCR, but fewer B. pilosicoli positive samples. An
      atypical strongly haemolytic isolate was detected only by CBT.

PMID- 16457901
TI  - Recommendations on detectors and quality control procedures for brachytherapy
      beta sources.
AB  - BACKGROUND AND PURPOSE: It is estimated that one third of the institutes applying
      clinical beta sources does not perform independent dosimetry. The Netherlands
      commission on radiation dosimetry (NCS) recently published recommended quality
      control procedures and detectors for the dosimetry of beta sources. The main
      issues of NCS Report 14 are summarized here. MATERIALS AND METHODS: A dosimetry
      survey was performed among 23 institutes in The Netherlands and Belgium. Well
      ionization chambers, a plastic scintillator, plane-parallel ionization chamber,
      diode and radiochromic film were used for determination of source strength (dose
      rate at reference distance) and uniformity of intravascular and ophthalmic
      sources. The source strength of multiple sources of each type was measured and
      compared with the source strength specified by the manufacturer. RESULTS: The
      standard deviation of the difference between measured and specified source
      strength was mostly about 3%, but varied between 0.8 and 15.8% depending on
      factors such as source type, detector, phantom and manufacturers calibration. The
      average non-uniformity was about 7% for intravascular sources and 20% for
      ophthalmic sources. It is estimated that the total relative standard uncertainty
      can be kept below +/-4% (1 sigma) with all detectors tested. Maximum deviations
      in source strength of 10% and a non-uniformity below 10% (intravascular) and 30%
      (ophthalmic) are recommended. CONCLUSIONS: Dosimetric and non-dosimetric quality
      control procedures on beta sources are recommended. They enable standardized
      measurements, including the determination of relative source strength and non
      uniformity. Absolute calibrations depend on the future introduction of primary
      standards for clinical beta sources.

PMID- 16457902
TI  - Metabolism of amyloid beta peptide and pathogenesis of Alzheimer's disease.
      Towards presymptomatic diagnosis, prevention and therapy.
AB  - The conversion of what has been interpreted as "normal brain aging" to
      Alzheimer's disease (AD) via a transition state, i.e. mild cognitive impairment,
      appears to be a continuous process caused primarily by aging-dependent
      accumulation of amyloid beta peptide (Abeta) in the brain. This notion give us a
      hope that, by manipulating the Abeta levels in the brain, we may be able not only
      to prevent and cure the disease but also to partially control some very
      significant aspects of brain aging. Abeta is constantly produced from its
      precursor and immediately catabolized under normal conditions, whereas
      dysmetabolism of Abeta seems to lead to pathological deposition upon aging. We
      have focused our attention on elucidation of the unresolved mechanism of Abeta
      catabolism in the brain. In this review, we describe a new approach to prevent AD
      development by reducing Abeta burdens in aging brains through up-regulation the
      catabolic mechanism involving neprilysin that can degrade both monomeric and
      oligomeric forms of Abeta. The strategy of combining presymptomatic diagnosis
      with preventive medicine seems to be the most pragmatic in both medical and socio
      economical terms. We also introduce a novel non-invasive amyloid imaging approach
      using a high-power magnetic resonance imaging (MRI) for the presymptomatic
      diagnosis of AD.

PMID- 16457903
TI  - Use of ionic liquids as media for the biocatalytic preparation of flavonoid
      derivatives with antioxidant potency.
AB  - Biocatalytic preparation of acylated derivatives of flavonoid glycosides was
      performed using various immobilized lipases in two different ionic liquids,
      namely 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF(4)) and 1-butyl-3
      methylimidazolium hexafluorophosphate ([bmim]PF(6)). The influence of various
      reaction parameters on the performance and the regioselectivity of the
      biocatalytic process was pointed out, using as model reaction the acylation of
      naringin and rutin with vinyl butyrate, catalyzed by immobilized Candida
      antarctica lipase at 60 degrees C. The biocatalytic modification of flavonoids
      strongly depended on the ionic liquid used, the molar ratio of substrates, as
      well as the acyl donor chain length. The highest conversion yield (about 65%
      after 96 h of incubation) was obtained with short chain acyl donors (up to four
      carbon atoms), at a relatively high molar ratio (10-15) in both ionic liquids
      used. The amount of monoacylated flavonoid derivatives produced in a single-step
      biocatalytic process in [bmim]BF(4) was up to 5.5 g/L for monoacylated rutin and
      30 g/L for monoacylated naringin. The regioselectivity of the process was higher
      in [bmim]BF(4) than in [bmim]PF(6) or organic solvents. Reaction rates observed
      in ionic liquids were up to four times higher than those reported for organic
      media. The acylation of sugar moiety of rutin with various acyl donors affected
      its antioxidant potential towards both isolated LDL and total serum model in
      vitro. A significant increase of antioxidant activity was observed for rutin-4'''
      O-oleate.

PMID- 16457904
TI  - The effect of pegylated interferon-alpha on the treatment of lamivudine resistant
      chronic HBeAg positive hepatitis B virus infection.
AB  - BACKGROUND/AIMS: To determine the response to pegylated interferon-alpha
      treatment of HBeAg-positive hepatitis B patients with proven lamivudine
      resistance. METHODS: Sixteen HBeAg-positive HBV patients with YMDD mutations were
      treated with pegylated interferon. Median treatment duration was 52 weeks (range
      20-53), with a 26-week follow-up. RESULTS: Two of 16 (12.5%) patients
      seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA
      levels below 10log 5 copies/ml) together with biochemical (normalization of serum
      ALT levels) responses. Compared with the strong signal in all other patients,
      only these two patients had a faint signal in the lamivudine resistance assay.
      For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml
      (P = 0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml
      after treatment cessation. Similarly, elevated median ALT levels at baseline
      decreased with treatment but rebounded after the end of treatment. CONCLUSIONS:
      In the largest cohort study to date, pegylated interferon-alpha therapy showed
      marginal efficacy in the presence of lamivudine resistance but such therapy may
      be beneficial in patients with only small amounts of mutant virus. In our
      opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should
      be included in all future studies of pegylated interferon-alpha in chronic
      hepatitis B.

PMID- 16457905
TI  - Contaminant mass discharge estimation in groundwater based on multi-level point
      measurements: a numerical evaluation of expected errors.
AB  - Different methods for the field-scale estimation of contaminant mass discharge in
      groundwater at control planes based on multi-level well data are numerically
      analysed for the expected estimation error. We consider "direct" methods based on
      time-integrated measuring of mass flux, as well as "indirect" methods, where
      estimates are derived from concentration measurements. The appropriateness of the
      methods is evaluated by means of modelled data provided by simulation of mass
      transport in a three-dimensional model domain. Uncertain heterogeneous aquifer
      conditions are addressed by means of Monte-Carlo simulations with aquifer
      conductivity as a random space function. We investigate extensively the role of
      the interplay between the spatial resolution of the sampling grid and aquifer
      heterogeneity with respect to the accuracy of the mass discharge estimation. It
      is shown that estimation errors can be reduced only if spatial sampling intervals
      are in due proportion to spatial correlation length scales. The ranking of the
      methods with regard to estimation error is shown to be heavily dependent on both
      the given sampling resolution and prevailing aquifer heterogeneity. Regarding the
      "indirect" estimation methods, we demonstrate the great importance of a
      consistent averaging of the parameters used for the discharge estimation.

PMID- 16457906
TI  - High prevalence of nosocomial infections in rehabilitation units accounted for by
      urinary tract infections in patients with spinal cord injury.
AB  - This study (part of the nationwide French prevalence survey of 2001) was
      organized to investigate the prevalence and risk factors of nosocomial infections
      (NIs) and the resistant flora in patients hospitalized in rehabilitation units.
      Two hundred and eighty-six patients were included from two hospitals in the
      'Hospices Civils de Lyon' group. Patients were classified into those with and
      without a spinal cord injury (SCI). Seventy-eight (27.3%) patients had an SCI.
      They were younger and more often characterized by a low Activity of Daily Life
      score, bladder incontinence and chronic respiratory disease. Urinary
      catheterization and mechanical ventilation were more common in these patients.
      The NI prevalence rate was higher in the SCI group (21.8% vs 4.3%, P<0.00001),
      particularly for urinary tract infections (UTIs, 19.2% vs 3.4%, P<0.00001). There
      was a positive relationship between the number of risk factors and NI
      acquisition. Multi-variate analysis showed that the only independent risk factor
      for NI acquisition was indwelling urinary catheterization [odds ratio (OR):
      11.64, 95% confidence intervals (CI): 2.53-53.65, P=0.002]. Marginally
      significant factors were chronic kidney or liver disease (OR: 5.84, 95%CI: 0.80
      42.68, P=0.082) and SCI (OR: 2.97, 95%CI: 0.61-14.60, P=0.179). The prevalence of
      antibiotic-resistant micro-organisms was high (nine cases of resistant organisms
      for 31 infection sites), but there were no differences between the groups. The
      high rate of NIs, especially UTIs, in SCI patients was not due to an independent
      effect of SCI but was probably due to the high number of risk factors. These high
      risk patients need targeted NI surveillance.

PMID- 16457907
TI  - Chronic leptin infusion advances, and immunoneutralization of leptin postpones
      puberty onset in normally fed and feed restricted female rats.
AB  - Does leptin play a vital role in initiating puberty in female rats and can it
      overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty
      onset? Prepubertal female rats were chronically infused for 14 days with leptin
      (icv or sc) or leptin-antiserum (icv) while puberty onset was monitored by means
      of scoring the moment of vaginal opening (VO). Median VO age was higher (35 days
      versus 27 days) in FR animals but leptin levels at VO were significantly
      decreased (1.44 +/- 0.17 ng/ml versus 2.79 +/- 0.31 ng/ml). Centrally (icv) and
      peripherally (sc) infused leptin (1 microg/day) advanced VO age compared to FR
      controls (30 days versus 35 days and 31 days versus 41 days, respectively).
      Congruently, centrally (icv) administered leptin-antiserum (0.6 microg/day)
      delayed puberty onset. In normally fed rats median VO age was only marginally
      advanced (26 days versus 27 days) but only if leptin was applied centrally. The
      effects of FR on puberty onset are counteracted or even normalized by the
      infusion of leptin, whereas immunoneutralization of central leptin postpones
      puberty onset. We therefore conclude that central leptin is crucial for
      initiating puberty in female rats.

PMID- 16457908
TI  - Standards for education and training for interagency working in child protection
      in the UK.

PMID- 16457909
TI  - The sequence of vaccinations and increased female mortality after high-titre
      measles vaccine: trials from rural Sudan and Kinshasa.
AB  - OBJECTIVE: West African studies have hypothesized that increased female mortality
      after high-titre measles vaccine (HTMV) was due to subsequent diphtheria-tetanus
      pertussis (DTP) and inactivated polio vaccine (IPV) vaccinations. We tested two
      deductions from this hypothesis in HTMV studies from rural Sudan and Kinshasa;
      first, there should be no excess female mortality for HTMV recipients when DTP
      was not given after HTMV and second, excess female mortality should only be found
      among those children who received DTP after HTMV. STUDIES: The Sudanese trial
      randomised 510 children to Edmonston-Zagreb (EZ) HTMV, Connaught HTMV or a
      control vaccine (meningococcal). Both the Connaught HTMV and the control group
      received standard measles vaccine at 9 months. In the Kinshasa study 1023
      children received one dose of HTMV at 6 months or two doses at 312 and 912 months
      of age. FINDINGS: First, the Sudan trial is one of the few randomised studies of
      measles vaccine; the EZ HTMV group had lower mortality between 5 and 9 months of
      age than controls, the mortality ratio (MR) being 0.00 (p = 0.030). This effect
      was not due to prevention of measles infection. Second, both studies provided
      evidence that HTMV per se was associated with low mortality. In a combined
      analysis comparing both HTMV groups with controls, the HTMV groups had a MR of
      0.09 (0.01-0.71) between 5 and 9 months of age. In Kinshasa, the HTMV recipients
      who did not receive simultaneous DTP had an annual mortality rate of only 1.0%
      between 6 months and 3 years of age. Third, the female-male MR was related to
      subsequent DTP vaccinations. In Kinshasa, the female-male MR was only 0.40 (0.13
      1.27) among the HTMV recipients who did not receive further doses of DTP. In
      Sudan, the female-male mortality ratio in the EZ group was 3.89 (95% CI 1.02
      14.83) and the female-male MR increased with number of doses of DTP likely to
      have been given during follow-up (trend, p = 0.043). Fourth, in Kinshasa,
      mortality was higher among children who had received HTMV and DTP simultaneously
      than among children who had received HTMV alone (MR = 5.38 (1.37-21.2)).
      CONCLUSIONS: Measles vaccine is associated with non-specific beneficial effects.
      When not given with DTP, HTMV per se was associated with low mortality. Increased
      female mortality was not found among children who did not receive DTP after HTMV.
      Hence, our deductions were supported and the sequence or combination of
      vaccinations may have an effect on sex-specific mortality patterns in low-income
      countries.

PMID- 16457910
TI  - Porcine interleukin-3 enhances DNA vaccination against classical swine fever.
AB  - DNA vectors can be used to deliver vaccine antigens that stimulate effective
      protective immunity in mice, but in larger, outbred animal species, the
      protective efficacy is lower or large doses of DNA are required. These data
      demonstrate that porcine interleukin-3 (IL-3) when delivered to pigs by DNA
      vector or in low doses as recombinant protein, can enhance antibody responses to
      classical swine fever virus antigen expressed from co-delivered DNA, and improve
      the protective efficacy of the DNA vaccine. The effect was further enhanced when
      IL-3 was expressed as a fusion protein with the potyvirus coat protein. The
      adjuvant effect of IL-3 was compared to that of granulocyte-macrophage colony
      stimulating factor (GM-CSF) and IL-3 was shown to be at least as efficacious as
      GM-CSF. The response to IL-3 is novel and suggests, that at least in pigs, IL-3
      could be used as an adjuvant for DNA vaccines.

PMID- 16457911
TI  - Removal of a migrated dental implant from a maxillary sinus by transnasal
      endoscopy.
AB  - A 54-year-old woman presented with maxillary sinusitis as a result of the
      migration of an implant into the sinus. We removed it endoscopically through the
      nose.

PMID- 16457912
TI  - Bupivacaine as pre-emptive analgesia in third molar surgery: Randomised
      controlled trial.
AB  - We conducted a prospective, randomised study on the use of pre-emptive analgesia
      in 45 patients who had bilateral impacted third molars removed. Bupivacaine 0.5%
      with adrenaline 1:200,000 was injected on one side, the other side acting as
      control. A visual analogue scale was used to measure the extent of postoperative
      pain. There was a significant reduction (p = 0.05) in postoperative pain on the
      injected side at 6, 12, and 72 h and an overall reduction in pain up to 7 days.

PMID- 16457913
TI  - Changes in strain distribution of loaded proximal femora caused by different
      types of cementless femoral stems.
AB  - BACKGROUND: A number of clinically used total hip femoral implants are claiming a
      more or less physiologic load transfer, mostly without providing experimental
      data. To compare three clinically cementless total hip stems of fundamentally
      different design, the strain distribution before and after insertion in human
      cadaver femora was measured in vitro. METHODS: A conventional straight stem based
      on a distal anchorage concept, a so-called "anatomic" stem designed to have a
      proximal force transmission and a "stemless" femoral neck prosthesis were
      evaluated under similar loading conditions. Strain distribution was measured with
      tri-axial strain-gauge rosettes before and after implantation of the stems. The
      same bending moment was used in all femora tested to compare magnitude and
      direction of the resulting strains. FINDINGS: The straight and the "anatomic"
      stem both led to a decrease of the longitudinal strains in the proximal femur,
      while the femoral neck implant mainly led to an increase of measured strains on
      the lateral side of the greater trochanter. The observed medial strains were
      closer to physiological values in the "stemless" prosthesis than those of the two
      full-stem prosthesis. INTERPRETATION: The decrease in strains seen in the
      proximal region of the femora with implanted conventional hip prosthesis
      corresponds well to the decrease of bone density in this region noted in clinical
      follow-up studies. The more physiological strain at the inferior base of the neck
      seen in "stemless implant" may induce a remodelling process that better retains
      bone stock in that area. However, the increase of strains noted after
      implantation of this prosthesis require further investigation to assess the risk
      they may pose to bone failure.

PMID- 16457914
TI  - A kinematic and kinetic analysis of walking after total knee arthroplasty with
      and without patellar resurfacing.
AB  - BACKGROUND: Clarification of the indications for patellar resurfacing in total
      knee arthroplasty (TKA) is still necessary. Few studies of adequate power have
      evaluated functional differences between total knee arthroplasty with and without
      patellar resurfacing, in particular walking gait. This study aimed to identify
      clinically relevant differences in knee kinematic or kinetic parameters during
      level walking between total knee arthroplasty with and without patellar
      resurfacing, after controlling for pre-surgery gait parameters. METHODS:
      Kinematic and kinetic gait analysis of level walking was performed on 34 subjects
      (41 knees) before and 12-18 months after total knee arthroplasty with patellar
      resurfacing performed randomly. Linear regression analysis was used to examine
      the influence of patellar resurfacing upon gait variables whilst controlling for
      the corresponding pre-surgery measure. FINDINGS: The pre-surgery value was a
      moderate to strong significant predictor of all post-surgery temporal-spatial and
      kinetic gait parameters (p < 0.001-0.008), and most kinematic parameters (p <
      0.001-0.066). The addition of patellar resurfacing to the regression models did
      not improve the predictive power in any case. Only one parameter, knee flexion at
      heel-strike, displayed a difference near statistical significance between total
      knee arthroplasty with and without patellar resurfacing (10 degrees versus 7
      degrees respectively, p = 0.023). INTERPRETATION: Pre-surgery gait patterns are
      an important determinant of post-surgery gait. There are no clinically relevant
      differences in walking gait between total knee arthroplasty performed with or
      without patellar resurfacing, using the Profix design.

PMID- 16457915
TI  - Arthroscopic evaluation of cartilage degeneration using indentation testing-
      influence of indenter geometry.
AB  - BACKGROUND: It has been suggested that the early onset of cartilage degeneration
      might be detected with a handheld indentation probe during knee arthroscopy,
      prior to any visible change on the articular surface. Collagen degradation has
      been considered as the first sign of cartilage degeneration. Therefore, it is
      important to consider the collagen network as a distinct constituent in the study
      of arthroscopic evaluation of cartilage degeneration. METHODS: The tip of an
      arthroscopic probe (indenter) was modeled as rigid and in contact with a
      cartilage/bone disk of sufficiently large radius to simulate an indentation in a
      joint. A fibril-reinforced model of cartilage, including streaming potentials and
      distinct constitutive laws for the proteoglycan matrix and collagen network, was
      used to determine the contact mechanics of indenter and cartilage. The finite
      element package ABAQUS was employed to obtain numerical solutions. FINDINGS: A
      spherical indenter produces a relatively uniform deformation in cartilage, but
      can easily slide on the articular surface. In contrast, a cylindrical indenter
      produces great deformation gradients for quick compression rates, but does not
      slide as easily on the articular surface as the spherical indenter. Small porous
      and large solid indenters should be used to evaluate the properties of the
      proteoglycan matrix and collagen network, respectively, in order to minimize or
      maximize the fluid pressure in the corresponding case. When the collagen network
      is substantially degraded, the gradients of fluid pressure and deformation are
      greatly reduced regardless of indenter geometry. INTERPRETATION: The indenter
      geometry including its porosity is important to the material safety of articular
      cartilage in indentation and precise evaluation of cartilage degeneration.

PMID- 16457916
TI  - Cu and Zn adsorption onto non-residual and residual components in the natural
      surface coatings samples (NSCSs) in the Songhua River, China.
AB  - Natural surface coatings samples (NSCSs) from the surface of river shingles were
      employed to investigate the roles of non-residual and residual components of the
      NSCSs in controlling Cu and Zn adsorption via the selective extraction techniques
      and statistical analysis. The results indicate that the greatest contribution to
      metals adsorption on a molar basis was from Mn oxides in the non-residual
      fraction. Metals adsorption capacities of Mn oxides exceeded those of Fe oxides
      by one order of magnitude, fewer roles were found attributing to adsorption by
      organic materials (OM), and the estimated contribution of the residual fraction
      to metals adsorption was insignificant. These results implied that Mn oxides were
      the most important component in controlling heavy metals in aquatic environments.
      Experiments with Cu and Zn adsorption measured together showed that Cu severely
      interfered with Zn adsorption to the NSCSs and vice versa under the conditions of
      the two coexisted ions adsorption.

PMID- 16457917
TI  - Fixation of metals in soil constituents and potential remobilization by
      hyperaccumulating and non-hyperaccumulating plants: results from an isotopic
      dilution study.
AB  - In this study isotopic dilution methods were used to investigate the hypothesis
      that access to metals associated with specific chemical components in the soil
      that are not available to non-accumulator species could be involved in
      hyperaccumulation. The hyperaccumulator Thlaspi caerulescens and a non
      accumulator species, Brassica napus, were grown in Cd and Zn enriched soil
      components calcite, goethite, charcoal and cryptomelane. The metal enriched
      components were aged to allow transformation of a proportion of added metals to
      non-labile forms. Results from the isotopic dilution L value method showed that
      despite taking up more metals, T. caerulescens accessed the same pool of metals
      as B. napus. Hence differential access to different solid-phase pools of metals
      appears to be an unlikely mechanism underlying metal hyperaccumulation. For all
      components except charcoal, L values for Cd and Zn were greater than the
      corresponding E values suggesting that E values may tend to underestimate the
      bioavailable fraction of metals in soils.

PMID- 16457918
TI  - Low levels of persistent organic pollutants (POPs) in New Zealand eels reflect
      isolation from atmospheric sources.
AB  - Polychlorinated biphenyls (PCBs) and organic pesticides (i.e., DDTs) were
      measured in long finned eels (Anguilla dieffenbachii) in 17 streams on the west
      coast of South Island, New Zealand. Very low levels of PCBs and low levels of
      ppDDE were found. The concentrations of PCBs and ppDDE were not correlated within
      sites indicating that different processes determined the levels of the two
      pollutants in New Zealand eels. The PCBs probably originate from atmospheric
      transport, ppDDE levels are determined by land use and are higher in agriculture
      areas. The low contamination level of these aquatic systems seems to be a
      function of a low input from both long and short-range transport as well as few
      local point sources. No correlation could be found between lipid content and
      persistent organic pollutants (POPs) concentration (as shown in previous studies)
      in the eels which could be explained by low and irregular intake of the
      pollutants.

PMID- 16457920
TI  - Changes in elemental composition and mass of atmospheric aerosol pollution
      between 1996 and 2002 in a Central European city.
AB  - Median atmospheric concentrations of Pb, Br, S, As, Se, and particulate matter
      (PM) decreased, and median concentrations of Sb, Cu, Zn, Fe, Ca, Cr and Ba
      increased in urban aerosol in downtown Budapest between 1996 and 2002. The
      changes in Pb and Br concentrations were unambiguously attributed to the phasing
      out of leaded gasoline. The increments were mainly related to and explained by
      non-exhaust vehicular emissions. The mechanical wear of asbestos-free brake
      linings of road vehicles contributed to the concentration of Cu and Sb on average
      by 69% and 66%, respectively in the PM10 size fraction. Tire rubber abrasion was
      a major source for atmospheric Zn; on average, non-crustal sources accounted for
      67% of Zn in the PM10 size fraction. Contribution of the tire wear component to
      the PM10 mass was estimated to be 6% at most, while its contribution to organic
      aerosol was of the order of 15%.

PMID- 16457919
TI  - Evidence for declining levels of heavy-metals in the Severn Estuary and Bristol
      Channel, U.K. and their spatial distribution in sediments.
AB  - Levels of heavy-metals (Cd, Cu, Cr, Ni, Pb and Zn) in suspended particulate and
      in surface and subsurface sediments were determined at seven locations in the
      Severn Estuary and Bristol Channel. Sediment metal concentrations were highest at
      sites close to industrial centres but levels have decreased significantly over
      the last 30 years so that they are now close to, or meet, environmental quality
      guidelines. The greatest metal concentrations in deposited sediments were usually
      associated with the finest particulates at locations with muddy sediments, but
      this was not always true at sites with predominantly sandy sediments. The metals
      bound to suspended particulates at all sites were remarkably consistent,
      presumably reflecting the mixing capacity of this macro-tidal estuary. The re
      exposure of older, more contaminated sediments could explain the observed
      differences between deposited and suspended material. Sediment redistribution due
      to strong seasonal currents might also explain the differences between winter and
      summer samples.

PMID- 16457921
TI  - Quantification of ozone uptake at the stand level in a Pinus canariensis forest
      in Tenerife, Canary Islands: an approach based on sap flow measurements.
AB  - Ozone uptake was studied in a pine forest in Tenerife, Canary Islands, an ecotone
      with strong seasonal changes in climate. Ambient ozone concentration showed a
      pronounced seasonal course with high concentrations during the dry and warm
      period and low concentrations during the wet and cold season. Ozone uptake by
      contrast showed no clear seasonal trend. This is because canopy conductance
      significantly decreased with soil water availability and vapour pressure deficit.
      Mean daily ozone uptake averaged 1.9 nmol m(-2) s(-1) during the wet and cold
      season, and 1.5 nmol m(-2) s(-1) during the warm and dry period. The
      corresponding daily mean ambient ozone concentrations were 42 and 51 nl l(-1),
      respectively. Thus we conclude that in Mediterranean type forest ecosystems the
      flux based approach is more capable for risk assessment than an external,
      concentration based approach.

PMID- 16457922
TI  - Saturation models of arsenic, cobalt, chromium and manganese bioaccumulation by
      Hyalella azteca.
AB  - Bioaccumulation of As, Co, Cr and Mn by the benthic amphipod Hyalella azteca in
      Burlington City tap (Lake Ontario) water was measured in 4-week tests.
      Bioaccumulation increased with exposure concentration and demonstrated an
      excellent fit to a saturation model (r(2): 0.819, 0.838, 0.895 and 0.964 for As,
      Co, Cr and Mn, respectively). The proportion of total body Mn eliminated during a
      24-h depuration period decreased as Mn body concentration increased, apparently
      due to a saturation of the elimination rate. The high maximum body concentration
      of 116,000 nmol g(-1) appears to result from the saturation of the Mn excretion
      which is slightly greater than the maximum Mn uptake rate. Elimination rates for
      As, Co and Cr were not dependent on body concentration. The four elements were
      not physiologically regulated in Hyalella. Their body concentrations should be
      good indicators of bioavailability and useful for environmental assessment.

PMID- 16457924
TI  - The health of nations in a global context: trade, global stratification, and
      infant mortality rates.
AB  - Despite the call for a better understanding of macro-level factors that affect
      population health, social epidemiological research has tended to focus almost
      exclusively on national-level factors, such as Gross Domestic Product per capita
      (GDP/c) or levels of social cohesion. Using a world-systems framework to examine
      cross-national variations in infant mortality, this paper seeks to emphasize the
      effects of global trade on national-level population health. Rather than viewing
      national-level health indicators as autonomous from broader global contexts, the
      study uses network analysis methods to examine the effects of international trade
      on infant mortality rates. Network data for countries were derived from
      international data on the trade of capital-intensive commodities in 2000. Using
      automorphic equivalence to measure the degree to which actors in a network
      perform similar roles, countries were assigned into one of six world-system
      blocks, each with its own pattern of trade. These blocks were dummy-coded and
      tested using ordinary least squares (OLS) regression. A key finding from this
      analysis is that after controlling for national-level factors, the two blocks
      with the lowest density in capital-intensive exchange, i.e., the periphery, are
      significantly and positively associated with national-level infant mortality
      rates. Results show the effects of peripherality and stratification on population
      health, and highlight the influence of broader macro-level factors such as trade
      and globalization on national health.

PMID- 16457923
TI  - Association between gross domestic product throughout the life course and old-age
      mortality across birth cohorts: parallel analyses of seven European countries,
      1950-1999.
AB  - Mortality levels of national populations have often been studied in relation to
      levels of gross domestic product (GDP) at time of death. Following the life
      course perspective, we assessed whether old-age mortality levels for subsequent
      cohorts are differentially associated with GDP levels prevailing at different
      ages of the cohorts. We used all-cause and cause-specific mortality data by sex,
      age at death (65-99), year at death (1950-1999), and year of birth (1865-1924)
      for Denmark, England and Wales, Finland, France, the Netherlands, Norway, and
      Sweden. Trends in national GDP per capita between 1865 and 1999 were
      reconstructed from historical national accounts data. Through Poisson regression
      analyses, we determined for each country both univariate and multivariate
      associations across five-year birth cohorts between mortality and GDP levels
      prevailing at time of death, and at earlier ages of the cohorts (i.e. 0-5, 6-19,
      20-49, and 50-64). For the subsequent cohorts, levels of GDP at time of death
      were strongly inversely associated with all-cause mortality, especially among
      women, and among men in England and Wales, Finland, and France. In most
      countries, stronger associations were observed with GDP levels prevailing at
      earlier ages of the cohorts. After control for GDP at time of death, these
      associations remained. An independent association of GDP at earlier ages of the
      cohort was also observed for cause-specific mortality. The associations were
      negative for ischaemic heart diseases, cerebrovascular diseases, and stomach
      cancer. They were positive for prostate cancer, breast cancer, COPD (women), and
      lung cancer (women). GDP prevailing at ages 20-49 (men) and ages 50-64 (women)
      had the largest associations with old-age mortality. These findings suggest an
      independent, mostly negative effect of GDP prevailing at earlier ages of
      subsequent cohorts on old-age mortality. Socio-economic circumstances during
      adulthood and middle age seem more important in determining old-age mortality
      trends than those during infancy or childhood.

PMID- 16457925
TI  - Rethinking John Snow's South London study: a Bayesian evaluation and
      recalculation.
AB  - Famously, John Snow attempted to convince a critical professional audience that
      public water supplied to South London residents by private companies was a
      principal vector for the transmission of cholera. The result has been called the
      sine qua non of the "epidemiological imagination," a landmark study still taught
      today. In fact, Snow twice attempted to prove public water supplies spread
      cholera to the South London population. His first, published in 1855, suffered
      from an incomplete data set that limited its descriptive and predictive import.
      In 1856, armed with new data, Snow published a more definitive study. This paper
      describes a previously unacknowledged methodological and conceptual problem in
      Snow's 1856 argument. We review the context of the South London study, identify
      the problem and then correct it with an empirical Bayes estimation (EBE)
      approach. The result hopefully revitalizes Snow's research as a teaching case
      through the application of a contemporary statistical approach.

PMID- 16457926
TI  - Effects of selective dopamine D4 receptor antagonist, L-741,741, on sleep and
      wakefulness in the rat.
AB  - The influence of the dopamine system upon sleep/wake states is not fully
      understood. To date, the role of dopamine D4 receptor has not been studied. The
      aim of this work is to study the influence of dopamine D4 receptor upon
      sleep/wake states in male rats. Male Wistar rats were implanted with
      electroencephalography and electromyography electrodes for sleep recording.
      Sleep/wake times were compared in rats first treated with control solution
      (vehicle) and the day after treated with a potent and highly selective D4
      dopamine receptor antagonist. L-741,741 (1.5, 3, 6 mg/kg) or vehicle solution
      (10% DMSO in saline) was administered intraperitoneally at the beginning of the
      light period. Subsequently, 3 h of polysomnography were recorded and sleep-wake
      parameters evaluated. For statistical comparisons, Wilcoxon ranges test was
      performed. L-741,741 (1.5 mg/kg) only increased Light Slow Wave Sleep (SWS). 3
      mg/kg enhanced Quiet Waking (QW) increasing number of episodes, whereas Active
      Waking (AW) was reduced decreasing mean episode duration. 6 mg/kg reduced number
      of episodes of Deep SWS and increased its latency. Light SWS was decreased
      reducing number of episodes and their duration. Total time spent asleep was
      reduced and time spent in AW was increased. REM latency was increased. These
      results suggest a role for D4 receptors in the regulation of wake and sleep.

PMID- 16457927
TI  - Current animal models of obsessive compulsive disorder: a critical review.
AB  - During the last 30 years there have been many attempts to develop animal models
      of obsessive compulsive disorder (OCD), in the hope that they may provide a route
      for furthering our understanding and treatment of this disorder. The present
      paper reviews current genetic, pharmacological and behavioral animal models of
      OCD, and evaluates their face validity (derived from phenomenological similarity
      between the behavior in the animal model and the specific symptoms of the human
      condition), predictive validity (derived from similarity in response to
      treatment) and construct validity (derived from similarity in the underlying
      mechanisms--physiological or psychological).

PMID- 16457928
TI  - NMR-based metabonomic study on the subacute toxicity of aristolochic acid in
      rats.
AB  - The subacute toxicity of aristolochic acid (AA) was investigated by (1)H NMR
      spectroscopic and pattern recognition (PR)-based metabonomic methods. Model
      toxins were used to enable comparisons of the urinary profiles from rats treated
      with known toxicants and AA at various time intervals. Urinary (1)H NMR spectra
      were data-processed and analyzed by pattern recognition method. The result of
      visual comparison of the spectra showed that AA caused a renal proximal tubular
      and papillary lesion and a slight hepatic impair. Pattern recognition analysis
      indicated that the renal proximal tubule lesion was the main damage induced by
      AA, and the renal toxicity induced by AA was a progressive course with the
      accumulation of dosage by monitoring the toxicological processes from onset,
      development and part-recovery. These results were also supported by the
      conventional clinical biochemical parameters.

PMID- 16457929
TI  - Analysis of multivariate extreme intakes of food chemicals.
AB  - A recently published multivariate Extreme Value Theory (EVT) model is applied to
      the estimation of population risks associated with dietary intake of pesticides.
      The objective is to quantify the acute risk of pesticide intake above a threshold
      and relate it to the consumption of specific primary food products. As an example
      daily intakes of a pesticide from three foods are considered. The method models
      and extrapolates simultaneous intakes of pesticide, and estimates probability of
      exceeding unobserved large intakes. Multivariate analysis was helpful in
      identifying whether the avoidance of certain food combinations would reduce the
      likelihood of exceeding a threshold. We argue that the presented method can be an
      important contribution to exposure assessment studies.

PMID- 16457930
TI  - Mechanism of DNA damage induced by bromate differs from general types of
      oxidative stress.
AB  - A representative reactive oxygen species (ROS), hydroxyl radical (*OH), is a
      highly reactive species and induces DNA backbone breakage. *OH also oxidizes
      every DNA base. The interaction of *OH with guanine leads to the generation of
      not only piperidine-resistant 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) but
      also various piperidine-labile products. On the other hand, potassium bromate
      (KBrO3) induces specific formation of 8-oxodG in the presence of SH compounds,
      such as glutathione (GSH) and cysteine (Cys). GSH/Cys reduces KBrO3 (BrO3-) to
      BrO2, which abstracts one electron from guanine. The one-electron oxidation of
      guanine may yield cation radicals followed by the reaction with a water molecule,
      leading to 8-oxodG formation. Therefore, mechanism of bromate-induced oxidative
      DNA damage is different from general types of oxidative stress such as *OH.

PMID- 16457931
TI  - Colchicine antimitosis causes progression of S-(1,2-dichlorovinyl)-L-cysteine
      induced injury leading to acute renal failure and death in mice.
AB  - Objective of the present study was to test the importance of tissue repair in the
      final outcome of S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced nephrotoxicity
      using colchicine (CLC) intervention. Male Swiss Webster (SW) mice were
      administered a normally nonlethal dose of DCVC (30 mg/kg, i.p.) on day 0 and CLC
      (2 mg/kg, i.p.) at 42 and 66 h after administration of DCVC. The mice were
      observed for mortality and various renal injury and repair parameters were
      studied during a time course of 0-14 days. Administration of 30 mg DCVC/kg led to
      loss of renal architecture by day 1, which sustained until day 5, and regressed
      thereafter to reach normal architecture by day 10 resulting in 100% survival.
      Renal dysfunction as assessed by increases in plasma BUN and creatinine levels
      was concordant during this time course. Urinary volume increased significantly
      between days 10 and 14 with significant increases in urinary glucose
      concentrations on days 1-4. Calpain leakage increased from day 1 and remained so
      until day 5 before declining at later time points. In contrast, CLC intervention
      led to marked inhibition of S-phase DNA synthesis and 100% mortality by 120 h.
      H&E sections of kidneys revealed loss of renal architecture on day 1 which
      progressively worsened from day 2 to 4. Polyuria and glycosuria were evident
      during the first 2 and 3 days, respectively. Calpain immunohistochemistry
      revealed progressive leakage of calpain in the extracellular space during 2-4
      days which lead to increased renal injury as evident from significant increases
      in calpain specific breakdown products (CSBPs) of alpha-fodrin during the same
      period of time. The group of mice receiving 2 mg CLC/kg alone showed a
      significant increase in urinary creatinine concentration on day 5. Neither the
      expression nor localization of aquaporin 1 was altered in any of the treatment
      groups. These results show that antimitotic intervention after DCVC-initiated
      renal injury leads to expansion and progression of that injury, which appears to
      be due to proteolytic destruction of neighboring cells mediated by calpain
      leaking out of necrosed renal tubular epithelial cells.

PMID- 16457932
TI  - The effects of teaching basic cardiopulmonary resuscitation--a comparison between
      first and sixth year medical students.
AB  - The purpose of this study was to check if medical students of one of the
      Universities of Medical Sciences in Poland are prepared to do basic
      cardiopulmonary resuscitation. The research was undertaken on groups of 50 first
      year students and 50 sixth year students at the time when they take an exam. To
      have wider insight into students' ability to perform basic cardiopulmonary
      resuscitation, quantitative and qualitative methods were used. Students'
      knowledge of resuscitation was checked by a written test including open
      questions, their skills of doing resuscitation were checked on manikins. Students
      also completed a questionnaire. The results showed that first year medical
      students have a better knowledge of basic cardiopulmonary resuscitation compared
      with sixth year students. The skills of advanced cardiopulmonary resuscitation
      are better in sixth year students compared with first year students. The study
      showed that skills of ventilation and chest compressions need more practice. The
      students' own estimation of the ability to perform cardiopulmonary resuscitation
      both in the first and sixth years is very high, but it does not correlate with
      their knowledge and skills. Our conclusions indicate the need to improve the
      programme of teaching cardiopulmonary resuscitation with a refresher course in
      theory and skills at least once a year.

PMID- 16457934
TI  - Terminology used to describe volume expanding resuscitation fluid.
AB  - Many published reports state that the type of resuscitation fluid to be used for
      volume expansion should be "isotonic crystalloid" or "isotonic fluid". Generally,
      this terminology refers to normal saline (NS) and lactated Ringer's (LR)
      solution. This terminology is suboptimal technically since not all "isotonic"
      crystalloids are sufficient volume expanders. A total of 48 reference books from
      the areas of general pediatrics, pediatric emergency medicine, emergency
      medicine, pediatric critical care, pediatric surgery, general surgery, internal
      medicine, family medicine, adult critical care, obstetrics and gynecology,
      endocrinology, and life support course manuals were reviewed. The description of
      fluids for hypovolemic shock, trauma, and diabetic ketoacidosis resuscitation was
      accurate in 46% of the time.

PMID- 16457933
TI  - A new device producing manual sternal compression with thoracic constraint for
      cardiopulmonary resuscitation.
AB  - OBJECTIVE: Blood flow during conventional cardiopulmonary resuscitation (CPR) is
      usually less than adequate to sustain vital organ perfusion. A new chest
      compression device (LifeBelt) which compresses both the sternum and the lateral
      thoraces (compression and thoracic constraint) has been developed. The device is
      light weight, portable, manually powered and mechanically advantaged to minimize
      user fatigue. The purpose of this study was to evaluate the mechanism of blood
      flow with the device, determine the optimal compression force and compare the
      device to standard manual CPR in a swine arrest model. METHODS: Following
      anesthesia and instrumentation, intravascular contrast injections were performed
      in four animals and the performance characteristics of the device were evaluated
      in eight animals. In a comparative outcome study, 42 anesthetized and
      instrumented swine were randomized to receive LifeBelt or manual CPR. Ventricular
      fibrillation (VF) was induced electrically and was untreated for 7.5 min. After
      7.5 min, countershocks were administered and chest compressions initiated.
      Pulseless electrical activity (PEA) was observed after one to three shocks in all
      animals. CPR was continued until restoration of spontaneous circulation (ROSC) or
      for 10 min after the first shock. If ROSC had not occurred within 5 min of
      beginning CPR, 0.01 mg/kg of epinephrine (adrenaline) was administered. During
      CPR, peak systolic aortic pressure (Ao), diastolic coronary perfusion pressure
      (CPP-diastolic aortic minus diastolic right pressure) and end-tidal CO(2) were
      measured. RESULTS: Angiographic studies demonstrated cardiac compression as the
      mechanism of blood flow. Optimal performance, determined by coronary perfusion
      pressure, was observed at a sternal force of 100-130 lb (45-59 kg). In the
      comparative trial, significant differences in the measured CPP were observed
      between LifeBelt and manual CPR both at 1 min (15+/-8 mmHg versus 10+/-6 mmHg,
      p<0.05) and 5 min (17+/-4 mmHg versus 13+/-7 mmHg, p<0.02) of chest compression.
      A greater (p<0.05) ETCO(2), a marker of cardiac output and systemic perfusion,
      was observed with LifeBelt CPR (20+/-7 mmHg) than with manual CPR (15+/-5 mmHg)
      at 1 min. Peak Ao pressures were not different between methods. With the device,
      86% of animals were resuscitated compared to 76% in the manual group.
      CONCLUSIONS: Blood flow with the LifeBelt device is primarily the result of
      cardiac compression. At a sternal force of 100-130 lb (45-59 kg), the device
      produces greater CPP than well-performed manual CPR during resuscitation from
      prolonged VF.

PMID- 16457935
TI  - The quality of chest compressions by trained personnel: the effect of feedback,
      via the CPREzy, in a randomized controlled trial using a manikin model.
AB  - Even after training, the ability to perform effective cardiac compressions has
      been found to be poor and to decrease rapidly. We assessed this ability with and
      without a non-invasive feedback device, the CPREzy, during a 270s CPR session in
      an unannounced, single-blinded manikin study using 224 hospital employees and
      staff chosen at random and using a non-cross over design. The two groups self
      assessed their knowledge and skills as adequate. However, the control group
      (N=111) had significantly more difficulty in delivering chest compressions deeper
      than 4 cm (25 versus 1 candidate in the CPREzy group), P=0.0001. The control
      group compressed ineffectively in 36% (+/-41%) of all compressions as opposed to
      6+/-13% in the CPREzy group (N=112, P=0.0001). If compressions were effective
      initially, the time until >50% of compressions were less than 4 cm deep was 75+/
      81s in the control group versus 194+/-87 s in the CPREzy group (P=0.0001 [-180 to
      -57.5]). After a few seconds of training in its use, our candidates used the
      CPREzy effectively. Against the background knowledge that estimation of
      compression depth by the rescuer or other team members is difficult, and that
      performing effective compressions is the cornerstone of any resuscitation
      attempt, our data suggests that a feedback device such as the CPREzy should be
      used consistently during resuscitation.

PMID- 16457936
TI  - Hypotension, bradycardia and syncope caused by honey poisoning.
AB  - Honey intoxication, a kind of food poisoning, can be seen in the Black Sea region
      of Turkey and in various other parts of the world as well. In this study, 66
      patients were hospitalized with a variety of symptoms including nausea, vomiting,
      salivation, dizziness, weakness, hypotension, bradycardia and syncope several
      hours after the ingestion of small amounts of honey. All patients had
      hypotension, and majority had bradycardia. These features resolved completely in
      24 h with i.v. fluids and atropine, and none died. In conclusion, honey poisoning
      should be taken into consideration in the differential diagnosis of acute
      myocardial infarction and in the patients with vomiting, hypotension and
      bradycardia.

PMID- 16457937
TI  - A case of prolonged life support.

PMID- 16457938
TI  - The common organization of the amygdaloid complex in tetrapods: new concepts
      based on developmental, hodological and neurochemical data in anuran amphibians.
AB  - Research over the last few years has demonstrated that the amygdaloid complex in
      amniotes shares basic developmental, hodological and neurochemical features.
      Furthermore, homolog territories of all main amygdaloid subdivisions have been
      recognized among amniotes, primarily highlighted by the common expression
      patterns for numerous developmental genes. With the achievement of new technical
      approaches, the study of the precise neuroanatomy of the telencephalon of the
      anuran amphibians has been possible, revealing that most of the structures
      present in amniotes are recognizable in these anamniotes. Thus, recent
      investigations have yielded enough results to support the notion that the
      organization of the anuran amygdaloid complex includes subdivisions with origin
      in ventral pallial and subpallial territories, a strong relationship with the
      vomeronasal and olfactory systems, abundant intra-amygdaloid connections, a main
      output center involved in the autonomic system, profuse amygdaloid fiber systems,
      and distinct chemoarchitecture. When all these new data about the development,
      connectivity and neurochemistry of the amygdaloid complex in anurans are taken
      into account, it becomes patent that a basic organization pattern is shared by
      both amniotic and anamniotic tetrapods.

PMID- 16457939
TI  - RACK1 has the nerve to act: structure meets function in the nervous system.
AB  - The receptor for activated protein kinase C 1 (RACK1) is an intracellular adaptor
      protein. Accumulating evidence attributes to this member of the tryptophan
      aspartate (WD) repeat family the role of regulating several major nervous system
      pathways. Structurally, RACK1 is a seven-bladed-beta-propeller, interacting with
      diverse proteins having distinct structural folds. When bound to the IP3
      receptor, RACK1 regulates intracellular Ca2+ levels, potentially contributing to
      processes such as learning, memory and synaptic plasticity. By binding to the
      NMDA receptor, it dictates neuronal excitation and sensitivity to ethanol. When
      bound to the stress-induced acetylcholinesterase variant AChE-R, RACK1 is
      implicated in stress responses and behavior, compatible with reports of RACK1
      modulations in brain ageing and in various neurodegenerative diseases. This
      review sheds new light on both the virtues and the variety of neuronal RACK1
      interactions and their physiological consequences.

PMID- 16457940
TI  - Change of the persistence lengths in the conformational transitions of pullulan-
      and amylose-tricarbanilates.
AB  - With raising temperature in the domain of 20 to 60 degrees C, the intrinsic
      viscosity [eta] for pullulan-tricarbanilate PTC and amylose-tricarbanilate ATC in
      solutions was found to decrease, indicating that they exhibited thermal-induced
      conformational transition from expanded form to compact form. The persistence
      length P(l) of the chains, evaluated with small-angle X-ray scattering, has also
      decreased as the temperature is raised and, moreover, it significantly depended
      on the solvents employed, where as P(l) of pullulan, having no carbanilate
      groups, has exhibited neither temperature- nor solvent-dependence. The
      temperature dependence of [eta] for PTC and ATC was well elucidated in terms of
      the temperature-dependent P(l) with the wormlike chain model. From these results,
      it is suggested that intramolecular hydrogen bonds would be formed between
      carbanilate groups neighboring along the backbone chain, but they are gradually
      and cooperatively collapsed as the temperature is raised, inducing the
      conformational transition.

PMID- 16457941
TI  - Antegrade versus retrograde endopyelotomy for pelvi-ureteric junction (PUJ)
      obstruction.
AB  - OBJECTIVES: To compare complication and success rates of antegrade and retrograde
      endopyelotomy performed over 10 years and to define possible risk factors
      associated with treatment failure. METHODS: From 1994 to 2004, 61 patients
      underwent a total of 68 endoscopic treatments: 19 antegrade and 49 retrograde
      endopyelotomy procedures. Antegrade endopyelotomy was always performed using
      diathermy. In the first 18 procedures retrograde endopyelotomy was performed
      using diathermy. In the most recent 30 procedures the incision was made using
      holmium laser. Endoluminal ultrasound was used in 78% of retrograde endopyelotomy
      and in 5% of antegrade endopyelotomy. RESULTS: The retrograde endopyelotomy
      patients demonstrated significantly lower complication rates (12.5% vs. 42%) and
      shorter hospital stay (1.5 vs. 7 days) than the antegrade endopyelotomy patients.
      The mean follow up of the patients who remained free from disease recurrence
      during the study period was 46 and 24 months for the antegrade and retrograde
      endopyelotomy group, respectively. The overall success rate (mean time to
      failure) of antegrade and retrograde endopyelotomy was 56% (31 months) and 70%
      (17 months), respectively. There was no statistically significant increase in the
      overall success rate of retrograde endopyelotomy using endoluminal ultrasound per
      se. Stratifying retrograde endopyelotomy by the type of energy used for the
      incision, the overall success rate (mean time to failure) was 80% (10 months) and
      53% (21 months) for Holmium laser and diathermy, respectively (p = 0.0626).
      CONCLUSIONS: The overall success of antegrade and retrograde endopyelotomy in
      this series appears to be largely a factor of lead-time bias and is similar
      enough to recommend retrograde endopyelotomy with holmium laser on the basis of
      its relative safety and shorter hospital stay.

PMID- 16457942
TI  - Magnetic resonance urethrography in comparison to retrograde urethrography in
      diagnosis of male urethral strictures: is it clinically relevant?
AB  - OBJECTIVE: To compare the clinical relevance of retrograde urethrography (RUG)
      and magnetic resonance (MR) urethrography in evaluating male urethral strictures.
      METHODS: Between January and April 2004, 20 men were referred to our institute
      for management of urethral strictures. The patients were investigated by
      conventional RUG and multiformat MR urethrography. The patients were examined by
      urethroscopy under anesthesia to be followed by definitive endoscopic or open
      operative intervention. The radiologic data were compared by endoscopic as well
      as operative findings in all the patients. RESULTS: Ten patients were managed by
      visual internal urethrotomy (VIU) and two by dilatation under anesthesia; two
      showed normal urethral caliber. Four patients required open urethral
      reconstructive procedures. Two patients underwent radical cystectomy and
      cutaneous diversion because of associated bladder or urethral malignancy.
      Although overall accuracy for diagnosis of urethral strictures was equal between
      both modalities (85%), MR urethrography provided extra clinical data in seven
      patients (35%). It was superior to RUG in judging the urethral stricture length
      in three patients, diagnosing a urethral tumor in one, detecting associated
      bladder mass in one, characterizing the site of urethra-rectal fistula in one,
      and accurately delineating the proximal urethra in the last patient. Unlike RUG,
      MR urethrography provided adequate information about the degree of
      spongiofibrosis in all patients. CONCLUSION: MR urethrography is a promising tool
      for defining male urethral strictures and can provide extra guidance for
      treatment planning that cannot be obtained with RUG.

PMID- 16457943
TI  - The difficult case in prostate cancer diagnosis--when is a "diagnostic TURP"
      indicated?

PMID- 16457944
TI  - Re: Edoardo Austoni, Vincenzo Mirone, Fabio Parazzini, Ciro Basile Fasolo, Paolo
      Turchi, Edoardo S. Pescatori, Elena Ricci and Vincenzo Gentile. Smoking as a risk
      factor for erectile dysfunction: data from the andrology prevention weeks 2001
      2002, a study of the italian society of andrology (S.I.A.). Eur Urol 2005;48:810
      8.

PMID- 16457945
TI  - Botulinum toxin--new mechanisms, new therapeutic directions?

PMID- 16457946
TI  - The choice between a therapy-induced long-term symptom and shortened survival due
      to prostate cancer.
AB  - OBJECTIVES: A patient with newly diagnosed localized prostate cancer can choose
      from an array of therapies. A patient's willingness to trade life for freedom
      from therapy-induced long-term symptoms is poorly investigated. METHODS: In
      October 2002, we attempted to collect information from the 591 men who had been
      diagnosed and registered with prostate cancer in 1999 in Stockholm County. In a
      postal questionnaire, men were asked to balance absence or presence of certain
      therapy-induced long-term symptoms against varying lengths of survival gain as a
      consequence of the therapy. RESULTS: Information was provided by 511 (86%) of the
      591 men. A large majority of the men participating in this study ended up in one
      of two extreme categories: either they accepted the therapy-induced symptom to
      gain survival or they did not. For fecal leakage, 78% of the men chose one of two
      extreme categories compared with 74% for urinary leakage, 71% for tender enlarged
      breasts, 73% for erectile dysfunction, and 78% for restricted diet. Thirty-seven
      percent of the men in the study were willing to accept fecal leakage if there was
      only the slightest chance to gain survival, comparing percentages for urinary
      leakage, tender enlarged breasts, restricted diet, and erectile dysfunction and
      were 48%, 53%, 55%, and 64%, respectively. CONCLUSION: Willingness to accept
      therapy-induced long-term symptoms to avoid a shortened survival due to prostate
      cancer varies dramatically among men with localized prostate cancer and a large
      majority of men are in one of two extreme categories. Among symptoms, long-term
      fecal leakage was the one fewest men were willing to accept to gain survival.

PMID- 16457947
TI  - Neuron-specific enolase and tau protein as neurobiochemical markers of neuronal
      damage are related to early clinical course and long-term outcome in acute
      ischemic stroke.
AB  - OBJECTIVES: Analyses of neuron-specific enolase (NSE) and tau protein in patients
      with hyperacute ischemic stroke, their association with infarct volume, severity
      of the neurological deficit, the neurovascular status and functional outcome.
      PATIENTS AND METHODS: In 66 consecutive patients, serial venous blood samples
      were taken at 3, 6, 12, 18, 24, 48, 72, 96, and 120 h after stroke onset. The
      neurovascular status was assessed by repetitive extra- and transcranial duplex
      sonography. Neurological deficits were quantified by the NIH stroke scale, and
      functional outcome was assessed with the modified Rankin scale (mRS). RESULTS:
      After a first rise within 3 h, NSE decreased followed by a secondary increase
      until Day 5. Tau protein concentrations showed a continuous increase from
      admission onward. NSE and tau release were highly correlated with severity of
      neurological deficits and infarct volume (P = 0.001). NSE, but not tau protein,
      release was associated to the neurovascular status on admission. NSE and tau
      protein values were significantly correlated with the functional outcome at 3
      months (P < 0.001). CONCLUSION: Release kinetics of NSE and tau protein are
      associated with patients' clinical deficits and infarct volume, and may be used
      as an additional predictor of the early course and functional outcome.

PMID- 16457948
TI  - Induction of thymidine phosphorylase expression by AZT contributes to enhancement
      of 5'-DFUR cytotoxicity.
AB  - Thymidine phosphorylase (TP) regulates intracellular thymidine metabolism and can
      enhance the anti-tumor effectiveness of 5'-deoxy-5-fluorouridine (5'-DFUR) by
      conversion of the pro-drug 5'-DFUR to 5-fluorouracil (5-FU) in tumor tissues. 5'
      DFUR is an effective anti-tumor drug in cells expressing high levels of TP. 3'
      Azido 3'-deoxythymidine (AZT) is a thymidine analog that has been proven useful
      in the treatment of acquired immunodefiency syndrome (AIDS). In this study, we
      found that AZT induces TP expression and enhances the sensitivity of human
      myeloid leukemia U937 cells to 5'-DFUR. Both the protein level and the activity
      of TP in U937 cells were elevated for 48h after exposure to AZT (20, 100 or
      300muM). AZT enhanced TP promoter activity in a dose-dependent manner. AZT also
      increased TP mRNA levels in U937 cells as assayed by Real-time reverse
      transcription PCR. AZT enhanced the cytotoxic effect of 5'-DFUR on U937 cells. A
      TP inhibitor, TPI, abrogated the cytotoxic activity of 5'-DFUR, and attenuated
      the combined cytotoxicity of AZT and 5'-DFUR. These results suggest that AZT
      enhances the cytotoxic effect of 5'-DFUR on U937 cells by upregulating TP
      activity in addition to its inhibition of thymidine kinase (TK) activity and
      reduction of intracellular dTTP pools.

PMID- 16457949
TI  - Presence of WT1 in nuclear messenger RNP particles in the human acute myeloid
      leukemia cell lines HL60 and K562.
AB  - The WT1 gene is a key player in acute myeloid leukaemia, in which it is
      frequently over-expressed. WT1 encodes a multifunctional zinc finger protein
      transcription factor, which also binds mRNA. Thus increasing evidence suggests
      that WT1 works both at the DNA and mRNA level, not only in the urogenital system
      but also in other contexts. Nuclear poly(A)(+) mRNP particles were isolated by
      oligo(dT) chromatography from the human acute myeloid leukemia cell lines HL60
      and K562, and analysed by Western blotting and 2D minigels. MALDI-TOF
      demonstrated the presence of hnRNP proteins, splice factors, and unexpectedly
      vimentin in the mRNP fraction. WT1 was also shown to be present in nuclear mRNP
      particles suggesting that in leukaemia, and by extension in all cancers in which
      it is involved, WT1 works both at the DNA and mRNA target level.

PMID- 16457950
TI  - Synergistic adsorption of phenol from aqueous solution onto polymeric adsorbents.
AB  - Adsorption of phenol from aqueous solution onto a nonpolar adsorbent, aminated
      adsorbent and weak base adsorbent (Amberlite XAD4, NDA103 and Amberlite IRA96C,
      respectively) at temperatures from 293 to 313K was studied for the weak
      interactions between the phenol molecules and the polymeric adsorbents. Isotherms
      of Langmuir and Freundlich equation with characteristic parameters for different
      adsorbents were well fitted to the batch equilibrium adsorption data. The
      adsorption capacity on NDA103 driven by hydrogen bonding and van der Waals
      interaction together is higher than that on IRA96C driven by hydrogen bonding
      interaction only and on XAD4 driven by van der Waals interaction only. For
      evaluating synergistic adsorption for phenol-water systems onto polymeric
      adsorbents, the adsorption capacity is normalized to the amounts of specific
      surface area and amino groups of adsorbents. The synergistic effect with other
      weak interactions would contribute more to the adsorption as acting
      simultaneously than that of acting individually.

PMID- 16457951
TI  - Molecular tools--advances, opportunities and prospects.
AB  - Modern molecular technologies are having a substantial impact in many fundamental
      and applied areas of parasitology. In particular, polymerase chain reaction (PCR)
      coupled approaches have found broad applicability because their sensitivity
      permits the enzymatic amplification of gene fragments from minute quantities of
      nucleic acids from tiny amounts of parasite material. Also, high-resolution
      electrophoretic and genomic methods are finding increased utility. This paper
      briefly discusses some developments and applications of DNA methods to parasites
      and highlights their usefulness or potential for those of veterinary importance.
      Selected examples of applications with implications in fundamental (systematics,
      population genetics, epidemiology and ecology) and applied (diagnosis, prevention
      and control) areas are presented. The focus is mainly on tools for the accurate
      identification of parasitic nematodes and protozoa of socio-economic importance,
      the diagnosis of infections and the detection of genetic variability using PCR
      coupled mutation scanning technology.

PMID- 16457952
TI  - Perinatal allopregnanolone influences prefrontal cortex structure, connectivity
      and behavior in adult rats.
AB  - Cortical neurosteroid levels vary dramatically across development; during the
      second week of life elevated levels of allopregnanolone are associated with
      decreased GABA(A) receptor function. Since GABA(A) receptor modulation plays a
      role in proliferative regulation in developing neocortex, it is possible that
      endogenous neurosteroids such as allopregnanolone, acting through GABA(A)
      receptors, modulate cortical development. We augmented normally low levels with
      exogenous administration of allopregnanolone (10 mg/kg) during the first week of
      rodent life. The localization of parvalbumin-labeled cells was markedly altered;
      the ratio of cell number in the deep (layers V-VI) vs. superficial (layers I-III)
      layers of adult prefrontal cortex increased two-fold in rats administered
      allopregnanolone on postnatal day 1 or 5. The mechanism underlying these
      anatomical changes likely involves GABA(A) receptors because similar changes in
      interneuron placement were observed after neonatal benzodiazepine administration.
      Measures of mature cortical function were also altered after neonatal
      neurosteroid administration, including [(3)H]MK-801 binding, prepulse inhibition
      and amphetamine-induced locomotor activity. Moreover, neonatal allopregnanolone
      administration increases the number of parvalbumin-expressing neurons in medial
      dorsal nucleus of the thalamus while the total neuron number is decreased. These
      findings suggest that connectivity between the medial dorsal nucleus of the
      thalamus and prefrontal cortex is likely altered by neonatal neurosteroid
      administration and may result in a disinhibited frontal cortex. Disinhibition in
      the prefrontal cortex is associated with behavioral changes relevant to human
      psychosis and developmental disorders. If neurosteroids play a role in normal
      development of prefrontal/medial dorsal patency as suggested by these studies,
      then alterations in neurosteroid levels may contribute to abnormal
      neurodevelopment.

PMID- 16457953
TI  - Continuous i.c.v. infusion of brain-derived neurotrophic factor modifies
      hypothalamic-pituitary-adrenal axis activity, locomotor activity and body
      temperature rhythms in adult male rats.
AB  - Brain-derived neurotrophic factor is a neurotrophin belonging to the nerve growth
      factor family, which is involved in the differentiation and survival of many
      types of neurons. It also participates in neuroprotection and neuronal plasticity
      in adult rats. Our previous studies showed that a single brain-derived
      neurotrophic factor injection modifies hypothalamic-pituitary-adrenal axis
      activity in adult male rats. To investigate the effect of chronic brain-derived
      neurotrophic factor administration on some physiological parameters, adult rats
      were implanted with osmotic micro-pumps to deliver brain-derived neurotrophic
      factor continuously for 14 days in the lateral ventricle (12 microg/day/rat).
      mRNA levels were evaluated by in situ hybridization analysis, peptide contents
      and plasma hormone concentrations by radioimmunoassay. Animals were also equipped
      with telemetric transmitters to study locomotor activity and temperature rhythms
      modifications, since hypothalamic-pituitary-adrenal axis is known to modulate
      these two parameters. Decreased body weight was used as a control of brain
      derived neurotrophic factor access to hypothalamic areas as already documented.
      In the hypothalamus the continuous brain-derived neurotrophic factor treatment
      increases: (i) the mRNA steady state levels of corticotropin releasing hormone
      and arginin-vasopressin in the paraventricular nucleus, the supraoptic nucleus,
      and the suprachiasmatic nucleus; (ii) the surface of corticotropin releasing
      hormone and arginin-vasopressin mRNA signals in these nuclei as detected by in
      situ hybridization, and (iii) the corticotropin releasing hormone and arginin
      vasopressin contents. The plasma concentrations of adrenocorticotropic hormone
      and corticosterone were decreased and increased, respectively. Finally, this
      treatment increased daily locomotor activity and temperature, and provoked some
      circadian perturbations. These results obtained after chronic brain-derived
      neurotrophic factor administration extend data on the brain-derived neurotrophic
      factor involvement in the hypothalamic-pituitary-adrenal axis regulation and
      illustrate its effects on the locomotor and temperature rhythms. They also allow
      demonstrating that the regulation of the hypothalamic-pituitary-adrenal axis by
      brain-derived neurotrophic factor differs according to the brain-derived
      neurotrophic factor administration mode, i.e. acute injection or chronic
      administration.

PMID- 16457955
TI  - Density and morphology of dendritic spines in mouse neocortex.
AB  - Dendritic spines of pyramidal cells are the main postsynaptic targets of cortical
      excitatory synapses and as such, they are fundamental both in neuronal plasticity
      and for the integration of excitatory inputs to pyramidal neurons. There is
      significant variation in the number and density of dendritic spines among
      pyramidal cells located in different cortical areas and species, especially in
      primates. This variation is believed to contribute to functional differences
      reported among cortical areas. In this study, we analyzed the density of
      dendritic spines in the motor, somatosensory and visuo-temporal regions of the
      mouse cerebral cortex. Over 17,000 individual spines on the basal dendrites of
      layer III pyramidal neurons were drawn and their morphologies compared among
      these cortical regions. In contrast to previous observations in primates, there
      was no significant difference in the density of spines along the dendrites of
      neurons in the mouse. However, systematic differences in spine dimensions (spine
      head size and spine neck length) were detected, whereby the largest spines were
      found in the motor region, followed by those in the somatosensory region and
      those in visuo-temporal region.

PMID- 16457954
TI  - Tolerance development to Morris water maze test impairments induced by acute
      allopregnanolone.
AB  - The progesterone metabolite allopregnanolone, like benzodiazepines, reduces
      learning and impairs memory in rats. Both substances act as GABA agonists at the
      GABA-A receptor and impair the performance in the Morris water maze test. Women
      are during the menstrual cycle, pregnancy, and during hormone replacement therapy
      exposed to allopregnanolone or allopregnanolone-like substances for extended
      periods. Long-term benzodiazepine treatment can cause tolerance against
      benzodiazepine-induced learning impairments. In this study we evaluated whether a
      corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats
      were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or
      two times a day, or for 7 days with allopregnanolone injections 20 mg/kg
      intraperitoneally, twice a day. Thereafter the rats were tested in the Morris
      water maze for 5 days and compared with relevant controls. Rats pretreated with
      allopregnanolone twice a day had decreased escape latency, path length and
      thigmotaxis compared with the acute allopregnanolone group that was pretreated
      with vehicle. Pretreatment for 7 days resulted in learning of the platform
      position. However, the memory of the platform position was in these tolerant rats
      not as strong as in controls only given vehicle. Allopregnanolone treatment was
      therefore seen to induce a partial tolerance against acute allopregnanolone
      effects in the Morris water maze.

PMID- 16457956
TI  - Developmental pattern of M1 and M2 muscarinic gene expression and receptor levels
      in cat carotid body, petrosal and superior cervical ganglion.
AB  - Using real-time reverse transcriptase polymerase chain reaction, Northern blot,
      and Western blot analyses, we evaluated the developmental pattern of mRNA and
      protein expression level of muscarinic M1 and M2 receptors in the carotid body,
      petrosal ganglion and superior cervical ganglion of 1-day, 15-day, 2-month-old
      and adult cats. mRNA expression and protein levels of tyrosine hydroxylase, the
      rate limiting enzyme for dopamine synthesis, were also assessed. Carotid body M1
      receptor mRNA, increased significantly by approximately 100% and 300% in 2-month
      and adult vs. 1- and 15-day-old cats, but protein level decreased gradually being
      approximately 50% lower compared with 1-day-old cats. In the petrosal ganglion,
      muscarinic M1 receptor mRNA level was higher in 15-day-old cats vs. 1-day-old, 2
      month-old and adult cats and protein levels were about 30% lower than in 1- and
      15-day-old cats. In the superior cervical ganglion, muscarinic M1 receptor mRNA
      was approximately 50% and 80% higher in 2-month-old and adult cats than 1- and 15
      day-old, but no changes in the protein level except in 15-day-old cats which was
      approximately 40% higher than 1-day-old. There was no change of muscarinic M2
      receptor mRNA or protein level in the carotid body or petrosal ganglion. However,
      in the superior cervical ganglion, the significant increase of mRNA of 30% and
      50% in 2-month-olds and adults, respectively was not associated with an increase
      in receptor protein. Tyrosine hydroxylase mRNA and protein level decreased
      significantly with age in the carotid body and petrosal ganglion. In the superior
      cervical ganglion, the age dependent increase in tyrosine hydroxylase mRNA was
      not associated with any changes in the protein level. These results show that the
      expression of muscarinic M1 and M2 receptors are age and organ-dependent in cats.
      Consequently, these changes may modulate chemosensory activity during development
      since muscarinic M1 receptor is predominantly involved in postsynaptic
      chemosensory activity, while muscarinic M2 receptor modulates acetylcholine and
      dopamine release from chemosensitive cells.

PMID- 16457957
TI  - Lead inhibited N-methyl-D-aspartate receptor-independent long-term potentiation
      involved ryanodine-sensitive calcium stores in rat hippocampal area CA1.
AB  - Lead exposure is known to be associated with cognitive dysfunction in children.
      Impairment of the induction of long-term potentiation (LTP) has been reported in
      area CA1 of rat hippocampus following lead exposure in vivo and in vitro. The
      present study was carried out to investigate whether the alterations of N-methyl
      d-aspartate (NMDA) receptor-independent LTP following lead exposure involve
      internal calcium stores in hippocampus CA1 synapses. Monosynaptic field
      excitatory postsynaptic potentials in hippocampal slice area CA1 were recorded
      using the whole-cell patch-clamp upon acute lead treatment, and these studies
      were coupled with calcium imaging experiments to observe internal calcium changes
      in cultured hippocampal neurons. Inhibiting calcium release by ryanodine
      significantly reduced NMDA receptor-independent LTP, and depletion of internal
      calcium stores with thapsigargin blocked this form of LTP. Caffeine, an agonist
      of ryanodine receptors, enhanced this form of LTP. However, caffeine-enhanced
      NMDA receptor-independent LTP was depressed after bath application of lead.
      Moreover, lead further decreased ryanodine- and thapsigargin-reduced NMDA
      receptor-independent LTP. Calcium imaging also confirmed that lead had an effect
      on internal calcium release and uptake. Taken together, these results
      demonstrated that lead inhibited NMDA receptor-independent LTP by action on
      calcium release and uptake by ryanodine-sensitive stores in rat hippocampal area
      CA1.

PMID- 16457958
TI  - NGF: a social molecule.

PMID- 16457959
TI  - Prevention profiles: Understanding youth who do not use substances.
AB  - This study replicates innovative profiles of prevention among students not using
      substances but who may be at different risks for acquisition. Using the
      Transtheoretical Model constructs of Decisional Balance and Temptations, cluster
      analyses were performed on four independent samples of students (n=1240) in the
      USA, England and Israel. For each sample, the same four distinct profiles
      emerged. ANOVAs indicated that the processes of prevention varied significantly
      across these profiles. The prevention profiles were extended to youth in
      Elementary, Middle, and High Schools and from a focus on single substances to
      multiple substances, including alcohol, tobacco, and illicit drugs. Implications
      for developing prevention programs are also discussed.

PMID- 16457960
TI  - Substance abuse amplifies the risk for violence in schizophrenia spectrum
      disorder.
AB  - The factors responsible for the association between schizophrenia and violence
      with or without co-occurring substance abuse have not been fully elucidated. The
      present study had two aims: (1) ascertain whether substance abuse augments the
      risk for violence in patients with schizophrenia; and, (2) determine whether
      violence is differentially related to positive and negative symptoms of
      schizophrenia. A sample of 133 adults were participated in this study. Patients
      with bizarre behavior and avolition-apathy symptoms were more likely to manifest
      violent behavior. In addition, patients with a history of criminal offenses and
      substance use disorder were more likely to exhibit violent behavior. Based on the
      results of this study, it is feasible to identify individual with schizophrenic
      spectrum disorder who are at high risk for violence.

PMID- 16457961
TI  - Tobacco dependence, risk perceptions and self-efficacy among Korean American
      smokers.
AB  - Psychosocial variables related to smoking cessation may differ among ethnic
      groups. This research focuses on Korean Americans, a group that receives little
      attention in smoking cessation research, yet has an elevated smoking rate when
      compared with that of the general US population. This article reports our
      findings on tobacco dependence, risk perceptions and self-efficacy and examines
      potential associations between these psychosocial variables and key demographic
      variables. One hundred Korean American adult smokers enrolled in the study and
      completed the psychosocial measurement. The majority of the participants (61%)
      were heavy smokers. The findings indicated that demographic factors were
      associated with key psychosocial variables that have been demonstrated to play a
      role in smoking cessation behaviors. In particular, younger age and higher
      educational level were associated with greater self-efficacy in quitting smoking.
      No differences in risk perception were observed by any of the demographic
      indicators assessed. The findings suggest that enhancing self-efficacy among
      older and less educated smokers may improve the efficacy of smoking cessation
      efforts that target Korean smokers.

PMID- 16457962
TI  - Predictors of persistent smoking and quitting among women smokers.
AB  - This study examined predictors of persistent tobacco smoking and smoking
      cessation in a longitudinal study of women's health. The sample consisted of 575
      women, with an average age of 34 years at baseline. Follow-up occurred some 13
      years later. Two models of smoking behavior were examined, the first identifying
      correlates of daily smoking at baseline and the second identifying predictors of
      subsequent quitting at follow-up among those smoking at baseline. Poor maternal
      education, being young at birth of first child, high level of anxiety, having a
      partner who smoked, and high tea/coffee consumption were all associated with
      smoking at baseline. Being a young mother and number of cigarettes smoked at
      baseline predicted subsequent persistent smoking while high levels of anxiety
      significantly predicted subsequent quitting.

PMID- 16457963
TI  - Initial evaluation of a real-world self-help smoking cessation programme for
      adolescents and young adults.
AB  - There is a lack of effective smoking cessation programmes for young people,
      despite the urgent need for them. The present study reports the initial results
      of a real-world self-help cessation programme which also contained a "quit and
      win"-contest component designed for adolescents and young adults. Consecutive
      registrants (N=1265) were surveyed 11 to 23 months after they registered to the
      programme to assess continuous abstinence. Results must be interpreted cautiously
      because this is an uncontrolled study with a 20.7% response rate (N=262). The
      programme was assessed positively by the participants. Results showed an 8.5%
      intention-to-treat quit rate with an average duration of 51.30 weeks continuous
      abstinence. Predictors for successful smoking were occasional smoking (not daily
      smoking) and older age.

PMID- 16457964
TI  - Nicotine dependence, use of illegal drugs and psychiatric morbidity.
AB  - The purpose of this study was to examine the association of smoking and nicotine
      dependence with psychiatric morbidity, controlling for the potential confounding
      effect of smoking on the relationship between the use of other substances and
      psychiatric morbidity. A sample of 290 adults were interviewed at a primary
      health centre (patients, 58%; patients' relatives, 34%; staff, 8%) to inquire
      about their tobacco, caffeine, alcohol, and illegal drug consumption. Psychiatric
      morbidity, defined by a score >6 on the General Health Questionnaire (GHQ-28),
      showed a strong direct association with nicotine dependence. The use of illegal
      drugs, but not of alcohol, was also strongly associated with psychiatric
      morbidity, after controlling for smoking. Both smoking and high nicotine
      dependence were also associated with use of caffeine, alcohol, cannabis and
      cocaine. High nicotine dependence may be considered as an expression of
      individual psychopathologic vulnerability. Tobacco may have a central
      facilitating role in the use of caffeine, alcohol, and illegal drug.

PMID- 16457965
TI  - Noninvasive monitoring of radiotherapy-induced microvascular changes using
      dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal
      tumor model.
AB  - PURPOSE: To examine dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) with a macromolecular contrast agent (P792) to visualize effects of
      radiotherapy (RT) on microvascular leakage in a colorectal cancer model. METHODS
      AND MATERIALS: CC531 tumors were induced in WAG/Rij rats. DCE-MRI was performed
      before and 5 days after 5 x 5 Gy of RT and parametric maps generated of the
      endothelial transfer constant (K(trans)) and the fractional interstitial space
      (Ve) according to the Tofts model. Tissue pO2 mapping was performed in each tumor
      core and rim before and after RT. Microvessel density (MVD), vascular endothelial
      growth factor (VEGF) expression, and pimonidazole hypoxia staining were compared
      with a control group of tumor-bearing rats. RESULTS: Mean K(trans) and v(e) were
      significantly reduced after RT in all tumor regions. Mean pO2 was 6.8 mm Hg
      before RT vs. 7.7 mm Hg after RT (p < 0.001) in the tumor rim and 3.5 mm Hg
      before RT vs. 4.4 mm Hg after RT (p < 0.001) in the tumor core. Mean MVD in the
      tumor rim was 10.4 in the RT treated group vs. 16.9 in the control group (p =
      0.061). VEGF expression was significantly higher in RT-treated rats. After RT, no
      correlation was found between DCE-MRI parameters and histologic parameters. A
      correlation was seen after RT between pO2 and K(trans) (r = -0.57, p = 0.08) and
      between pO2 and v(e) (r = -0.65, p = 0.04). CONCLUSIONS: Dynamic contrast
      enhanced-MRI with P792 allows quantification of microvascular changes in this
      colorectal model. RT significantly reduces neovascular leakage and enhances
      tissue oxygenation and VEGF expression. After RT, DCE-MRI parameters are related
      to tumor pO2, but not to MVD or VEGF expression.

PMID- 16457966
TI  - Body radiation exposure in breast cancer radiotherapy: impact of breast IMRT and
      virtual wedge compensation techniques.
AB  - PURPOSE: Recent reports demonstrate a dramatically increased rate of secondary
      leukemia for breast cancer patients receiving adjuvant high-dose anthracycline
      and radiotherapy, and that radiation is an independent factor for the development
      of leukemia. This study aimed to evaluate the radiation body exposure during
      breast radiotherapy and to characterize the factors associated with an increased
      exposure. PATIENTS AND METHODS: In a prospective cohort of 120 women, radiation
      measurements were taken from four sites on the body at the time of adjuvant
      breast radiotherapy. Multiple regression analysis was performed to analyze
      patient and treatment factors associated with the amount of scattered radiation.
      RESULTS: For standard 50 Gy breast radiotherapy, the minimal dose received by
      abdominal organs is on average 0.45 Gy, ranging from 0.06 to 1.55 Gy. The use of
      physical wedges as a compensation technique was the most significant factor
      associated with increased scattered dose (p < 0.001), resulting in approximately
      three times more exposure compared with breast intensity-modulated radiation
      therapy (IMRT) and dynamic wedge. CONCLUSIONS: The amount of radiation that is
      scattered to a patient's body is consistent with exposure reported to be
      associated with excess of leukemia. In accordance with the As Low As Reasonably
      Achievable (ALARA) principle, we recommend using breast IMRT or virtual wedging
      for the radiotherapy of breast cancer receiving high-dose anthracycline
      chemotherapy.

PMID- 16457967
TI  - Who attends skin cancer clinics within a randomized melanoma screening program?
AB  - BACKGROUND: Screening may reduce morbidity and mortality associated with
      melanoma, although in the absence of randomized-controlled trials, this remains
      unproven. METHODS: As part of a randomized community-based trial of melanoma
      screening in Queensland, Australia, sociodemographic characteristics, skin cancer
      risk factors and attitudes towards skin cancer associated with attendance at
      screening clinics and reasons for attendance or non-attendance were examined. A
      telephone survey was conducted among 743 attendees and 298 non-attendees.
      RESULTS: After adjustment, the following factors were associated with clinic
      attendance: age 40-49 years, having fair skin, a personal history of skin cancer
      or melanoma or concern about a specific spot or mole, and no recent whole-body
      skin examination by a doctor. The main reasons for attendance were "to see if I
      have melanoma", "to have a suspicious mole checked" or "to have a whole-body skin
      examination". The main reasons for non-attendance were lack of knowledge about
      the clinics, no time or being away while the clinics were held and having had a
      skin check in the recent past. Overall, 77% of non-attendees compared to 65% of
      attendees stated they planned to participate in future screening. CONCLUSIONS:
      The results suggest that we were able to attract both men and women equally to a
      skin screening clinic, along with those at all levels of education and indicate
      the importance of using well-designed promotional materials to attract community
      members to skin screening clinics. Future work should test strategies to remove
      barriers to participation in skin screening identified in this study.

PMID- 16457968
TI  - Effects of an extinguished CS on competition with another CS.
AB  - Three experiments were conducted using a conditioned taste aversion procedure
      with rats to examine the effect of nonreinforced presentations of a conditioned
      stimulus (CS) on its ability to compete with a target stimulus for manifest
      conditioned responding. Two CSs (A and B) were presented in a serial compound and
      then paired with the unconditioned stimulus. CS A was first paired with the US
      and then presented without the US (i.e., extinction) prior to reinforced
      presentation of the AB compound. Experiment 1 showed that A was poor at competing
      with B for conditioned responding when given conditioning and extinction prior to
      reinforcement of AB relative to a group that received both A and B for the first
      time during compound conditioning. That is, an extinguished A stimulus allowed
      greater manifest acquisition to B. Experiment 2 found that extinction treatment
      produced a poor CR to the pretrained and extinguished CS itself following
      compound conditioning. Experiment 3 found that interposing a retention interval
      after extinction of A and prior to compound conditioning enhanced A's ability to
      compete with B. The results of these experiments are discussed with regard to
      different theories of extinction and associative competition.

PMID- 16457969
TI  - Full genome sequence and analysis of Indian swine hepatitis E virus isolate of
      genotype 4.
AB  - The full-length genomic sequence of an Indian swine hepatitis E virus (HEV)
      isolate (IND-SW-00-01) recovered from feces of a pig experimentally infected with
      swine HEV pool from western India was determined. The genome consisted of 7,240
      nucleotides, excluding the poly (A) tail of at least 22 residues and contained
      three open reading frames (ORFs), ORF-1 encoding 1,707 amino acids, ORF-2
      encoding 674 amino acids and ORF-3 encoding 114 amino acids. Comparative full
      length genome sequence and phylogenetic analyses suggested that the Indian swine
      HEV represents a distinct variant among the genotype 4 isolates with a divergence
      of 15-16.6%. Analyses based on ORF-1, 2 and 3 as well as partial ORF-2 (227
      nucleotides) yielded similar results. As compared to type 4 HEV isolates, 26
      unique amino acid substitutions were recorded, 16 in ORF-1, 8 in ORF-2 and 2 in
      ORF-3. IND-SW-00-01 showed insertion of 'C' at 5159 position while all other type
      4 isolates have insertion of 'U' at the same position. Whether these changes
      contribute towards observed absence of type 4 HEV infections in Indian patients
      needs to be determined.

PMID- 16457970
TI  - Preterm birth--what are the relevant economic issues?

PMID- 16457971
TI  - Cost effectiveness of prevention and treatment of neonatal respiratory distress
      (RDS) with exogenous surfactant: what has changed in the last three decades?
AB  - In 1993, exogenous surfactant products were emerging as licensed treatments for
      respiratory distress syndrome (RDS), a leading cause of death in preterm newborn
      babies. Models of cost-effectiveness of alternative treatments showed surfactant
      to be an expensive but effective and also cost effective treatment. However the
      most efficient policy for use of surfactant depended on other parallel
      'technologies' such as giving antenatal corticosteroids where preterm delivery is
      anticipated. Following introduction into clinical practice, questions changed
      from whether to use surfactant, to when, and which product to use. The early
      models of cost effectiveness were dependent on the neonatal technology in use,
      and on the costs of neonatal care and prices of surfactant at the time. Little
      information was available about long term outcomes. The aims of this paper are to
      summarise the role of surfactant in the economics of newborn care since the late
      1980s; to observe the value of studies published in the early 1990s for current
      decisions; and to comment on recent and possible future economic studies of
      neonatal surfactant.

PMID- 16457972
TI  - Characterization and cytotoxicity of mixed polyethyleneglycol modified liposomes
      containing doxorubicin.
AB  - Liposomes are recognized as one of the useful drug carriers, but have many
      problems to overcome before their clinical application. Liposomes, bonding
      peculiarly with serum protein (opsonization), are taken up by reticuloendothelial
      system (RES) cells in the liver and spleen. It is known that polyethyleneglycol
      (PEG) modification of the liposome surface induces the formation of a fixed
      aqueous layer around the liposomes due to the interaction between the PEG-polymer
      and water molecule, and thus prevents the attraction of opsonins. Namely, PEG
      modified liposomes are able to escape trapping by the RES cells, and have a
      prolonged circulation time. In this study, the effects of different anchors with
      the same PEG molecular weight on the cell uptake and cytotoxicity of mixed PEG
      modified liposomal doxorubicin (DOX) were examined. The fixed aqueous layer
      thickness (FALT) of liposomes covered with mixtures of PEG-molecules which differ
      in their chain length were increased, compared to that of the single PEG2000
      modified liposome. Mixed PEG-modification of liposomes with different anchors
      (PEG2000-(1-monomethoxypolyethyleneglycol-2,3-distearoylglycerol (DSG):
      cholesterol (CHO)=1:1)-modified liposome) led to an increase in the FALT,
      compared to that of each single PEG-modification. The uptake of DOX into Ehrlich
      ascites carcinoma cells by the liposomes covered with PEG-CHO was higher than the
      other liposomes. Thus, liposomes covered with PEG-DSG and PEG-CHO have an
      enhanced cytotoxicity. In conclusion, it was confirmed that mix-modified
      liposomes using PEG-lipid with different anchors were superior.

PMID- 16457973
TI  - Long-circulating gadolinium-encapsulated liposomes for potential application in
      tumor neutron capture therapy.
AB  - Gadolinium neutron capture therapy (Gd-NCT) is a promising cancer therapy
      modality. One of the key factors for a successful Gd-NCT is to deliver and
      maintain a sufficient amount of Gd in tumor tissues during neutron irradiation.
      We proposed to prepare a Gd delivery system by complexing a Gd-containing
      compound, diethylenetriaminepentaacetic acid (Gd-DTPA), with a polycationic
      peptide, poly-L-lysine (pLL), and then encapsulate the complexed Gd-DTPA into
      PEGylated liposomes. Complexation of Gd-DTPA with pLL not only enhanced the
      encapsulation efficiency of Gd-DTPA in liposomes, but also significantly limited
      the release of Gd-DTPA from the liposomes. A Gd-DTPA-encapsulated liposome
      formulation that contained 6.8+/-0.3 mg/mL of pure encapsulated Gd was prepared.
      The blood half-life of the Gd encapsulated into the liposome formulation was
      estimated to be about 24 h in healthy tumor-free mice. About 12 h after the Gd
      encapsulated liposomes were intravenously injected into mice with pre-established
      model tumors, the Gd content in the tumors reached an average of 159 microg/g of
      wet tumor tissue. This Gd-DTPA encapsulated liposome may be used to deliver Gd
      into solid tumors for NCT and tumor imaging.

PMID- 16457974
TI  - In vivo human buccal permeability of nicotine.
AB  - The aim was to examine the in vivo buccal pH-dependent permeability of nicotine
      in humans and furthermore compare the in vivo permeability of nicotine to
      previous in vitro permeability data. The buccal permeability of nicotine was
      examined in a three-way cross-over study in eight healthy non-smokers using a
      buccal perfusion cell. The disappearance of nicotine from perfusion solutions
      with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of
      nicotine (P(app)) was determined at each pH value. Parotid saliva was collected
      in an attempt to assess systemic levels of nicotine. The disappearance rate of
      nicotine increased significantly as the pH increased, which resulted in P(app)
      values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(
      4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear
      relationship (R(2)=0.993) was obtained between the P(app) values and non-ionised
      nicotine, which indicates that the nicotine transfer occurred by means of passive
      diffusion. P(app) values of 0.60 x 10(-4) and 6.18 x 10(-4)cms(-1) were obtained
      for the mono-protonated and non-ionised species of nicotine, respectively. The
      analysis of the parotid saliva samples indicated that these samples might be
      useful in the assessment of systemic absorption of nicotine. Previous buccal in
      vitro models underestimated the in vivo human permeability of nicotine. However,
      the in vitro models were capable of predicting the effect of pH on the nicotine
      permeability.

PMID- 16457975
TI  - Neurotoxic flying foxes as dietary items for the Chamorro people, Marianas
      Islands.
AB  - Fanihi -- flying foxes (Pteropus mariannus mariannus, Pteropodidae) -- are a
      highly salient component of the traditional Chamorro diet. A neurotoxic, non
      protein amino acid, beta-methylamino-l-alanine (BMAA) accumulates in flying
      foxes, which forage on the seeds of Cycas micronesica (Cycadaceae) in Guam's
      forests. BMAA occurs throughout flying fox tissues both as a free amino acid and
      in a protein-bound form. It is not destroyed by cooking. Protein-bound BMAA also
      remains in cycad flour which has been washed and prepared by the Chamorro people
      as tortillas, dumplings, and thickened soups. Other animals that forage on cycad
      seeds may also provide BMAA inputs into the traditional Chamorro diet.

PMID- 16457976
TI  - Haplotype diversity of 16 Y-chromosomal STRs in three main ethnic populations
      (Malays, Chinese and Indians) in Malaysia.
AB  - We have analyzed 16 Y-STR loci (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19,
      DYS385a/b, DYS393, DYS391, DYS439, DYS635 or Y-GATA C4, DYS392, Y-GATA H4,
      DYS437, DYS438 and DYS448) from the non-recombining region of the human Y
      chromosome in 980 male individuals from three main ethnic populations in Malaysia
      (Malay, Chinese, Indian) using the AmpFlSTR((R)) Y-filertrade mark (Applied
      Biosystems, Foster City, CA). The observed 17-loci haplotypes and the individual
      allele frequencies for each locus were estimated, whilst the locus diversity,
      haplotype diversity and discrimination capacity were calculated in the three
      ethnic populations. Analysis of molecular variance indicated that 88.7% of the
      haplotypic variation is found within population and 11.3% is between populations
      (fixation index F(ST)=0.113, p=0.000). This study has revealed Y-chromosomes with
      null alleles at several Y-loci, namely DYS458, DYS392, DYS389I, DYS389II, DYS439,
      DYS448 and Y-GATA H4; and several occurrences of duplications at the highly
      polymorphic DYS385 loci. Some of these deleted loci were in regions of the Y(q)
      arm that have been implicated in the occurrence of male infertility.

PMID- 16457977
TI  - Equilibrium test findings in patients with Bell's palsy.
AB  - OBJECTIVE: We analyzed equilibrium test findings in patients with Bell's palsy to
      confirm that such findings occur not only in patients with Hunt's syndrome but
      also in patients with Bell's palsy. METHODS: Subjects were 83 patients with
      Bell's palsy, 45 patients with Hunt's syndrome, and 82 patients with unilateral
      chronic otitis media without history of vertigo or ear surgery (for control).
      They were treated in our inpatient department and underwent equilibrium testing
      during the period 1983-2002. All subjects were at least 20 years of age. The
      following were analyzed: (1) presence of vertigo, (2) presence of abnormal
      equilibrium test findings, (3) relation between the degree of paralysis and
      abnormal equilibrium test findings, and (4) relation between the degree of
      recovery from paralysis and abnormal equilibrium test findings. Equilibrium
      testing consisted of a gaze nystagmus test, a spontaneous nystagmus test,
      positional and positioning nystagmus tests, and a caloric test. The incidence of
      abnormal findings in each test was compared between the three groups. RESULTS:
      Abnormal equilibrium test findings were observed in patients with Bell's palsy.
      No association was observed between the results of equilibrium tests and the
      degree of facial paralysis in patients with Bell's palsy. However, some of the
      equilibrium test results were significantly associated with the degree of facial
      nerve recovery. CONCLUSIONS: Although our study was limited in its lack of true
      control subjects, our data suggest that patients with Bell's palsy show a
      significantly high incidence of vestibular abnormalities.

PMID- 16457978
TI  - Is there a molecular connection between hypoxia and aging?
AB  - Aging is associated with high incidence of ischemic diseases, which go along with
      a drop in tissue oxygenation. At the molecular level the hypoxia inducible factor
      (HIF) is the master regulator for hypoxia-induced gene expression. Recent studies
      demonstrated age-related changes in the HIF system, which might explain the
      reduced ability to cope with hypoxia in elderly. There are also some evidences
      that HIF is functionally connected to the aging process itself.

PMID- 16457979
TI  - Aging alters macrophage properties in human skeletal muscle both at rest and in
      response to acute resistance exercise.
AB  - Macrophages are involved in skeletal muscle repair through pro-inflammatory and
      alternative functions. We tested the hypothesis that aging alters the abundance
      and properties of skeletal muscle macrophages that will influence their
      functional response to acute resistance exercise. Total macrophages (CD 68+), as
      well as pro- (CD 11b+) and anti-inflammatory (CD 163+) subpopulations and
      associated cytokine mRNAs were quantified in vastus lateralis biopsies from young
      (N=17) and elderly (N=17) males pre- and 72 h post-exercise. Pre-exercise, young
      muscle tended to possess a greater number of macrophages, whereas elderly muscle
      possessed higher levels of IL-1 beta (P=0.001), IL-1 RA (P=0.003), and IL-10
      (P=0.028). Post-exercise, total macrophages did not change in either group,
      however, the number of CD 11b+ (P=0.039) and CD 163+ (P=0.026) cells increased 55
      and 29%, respectively, but only in the young. IL-1 beta (P=0.006), IL-10
      (P=0.016), and AMAC-1 (P=0.044) also increased, approximately two-fold, and again
      only in the young. Quantitation of CD 11b+ and CD 163+ cells suggests that the
      majority of resident macrophages possess alternative functions, and a small
      subpopulation participates in the inflammatory response. Both subpopulations
      increased their activity post-exercise, exclusively in the young. These findings
      suggest that aging results in a defective regulation of muscle macrophage
      function, both at baseline and in response to resistance exercise, that may limit
      muscle hypertrophy in older adults.

PMID- 16457980
TI  - PET imaging for evaluation of metastatic colorectal cancer of the liver.
AB  - Colorectal cancer is a major cause of cancer death in Western Europe and United
      States; the liver is the most common site for colorectal metastases. PET has an
      important role in the management of patients with colorectal liver metastases. It
      is an effective tool to detect hepatic metastases and to monitor the response to
      systemic and local therapy. The major impact of PET-CT over PET alone is the
      improvement in the certainty of lesion location. PET-CT has the unique advantage
      to combine functional and anatomic imaging in an integrated scanner; it allows a
      thoroughly evaluation of patients with colorectal liver metastases.

PMID- 16457981
TI  - Development and stability of semisolid preparations based on a supercritical CO2
      Arnica extract.
AB  - Conventional herbal drug preparations (HDP) based on Arnica montana L. have a low
      content of the active principles, sesquiterpene lactones, which show poor
      stability and low physical compatibility in semisolid formulations. Recently, an
      innovative supercritical carbon dioxide (CO2) extract with high sesquiterpene
      content has been marketed. Development of six semisolid preparations
      (cetomacrogol, polysorbate 60, polawax, anphyphil, natrosol and sepigel) based on
      this innovative CO2 extract is discussed. Stability of these preparations was
      investigated according to ICH guidelines. The evaluation of in vitro release of
      active constituents was performed using the cell method reported in the European
      Pharmacopoeia. Preliminary data on in vivo permeation of three selected
      formulations is demonstrated using the "skin stripping" test, according to the
      FDA, in healthy subjects. Analysis of sesquiterpene lactones within the extract
      and in vitro and in vivo studies was performed by RP-HPLC-DAD-MS method. The
      cetomacrogol showed the best release profile in the in vitro test, while in the
      in vivo test the best preparation resulted polysorbate 60 and polawax.

PMID- 16457982
TI  - Bioluminescent bacteria assay of veterinary drugs in excreta of food-producing
      animals.
AB  - The residues of pharmacological treatments on food-producing animals, present in
      the manure dispersed on agricultural land, can impact environmental and human
      health through toxic, genotoxic, and drug-resistance development effects.
      Biotoxicity assays can easily reveal the presence of noxious substances and those
      based on bioluminescent bacteria (BLB) are particularly simple and rapid. A BLB
      assay was developed as microplate format by using various strains of Vibrio sp.
      and was employed to evaluate their response to pure antibiotic solutions and to
      residues extracted from excreta of antibiotic treated pigs and turkeys. The
      residues were quantified by HPLC analysis. The BLB assay can be proposed as an
      easy-to-perform screening tool to assess the presence of residues due to
      undeclared current, or recently ended, pharmacological treatments, as well as to
      evaluate their permanence in manure.

PMID- 16457983
TI  - [Impact of legal definitions of paediatric intensive care medicine].

PMID- 16457984
TI  - Reverse transcriptase template switching and false alternative transcripts.
AB  - Reverse transcriptase (RT) can switch from one template to another in a homology
      dependent manner. In the study of eukaryotic transcripts, this propensity of RT
      can produce an artificially deleted cDNA, which can be wrongly interpreted as an
      alternative transcript. Here, we have investigated the presence of such template
      switching artifacts in cDNA databases, by scanning a collection of human splice
      sites (Information for the Coordinates of Exons, ICE database). We have confirmed
      several cases at the experimental level. Artifacts represent a significant
      portion of apparently spliced sequences using noncanonical splice signals but are
      rare in the context of the whole database. However, care should be taken in the
      annotation of alternative transcripts, especially when the RT used is poorly
      thermostable and when the putative intron is flanked by direct repeats, which are
      the substrate for template switching.

PMID- 16457986
TI  - From the urine of sacred cows to the laying on of hands and beyond--G. Paul Moore
      lecture.

PMID- 16457985
TI  - Perinatal ethanol exposure alters met-enkephalin levels of male and female rats.
AB  - This study used a rat model of Fetal Alcohol Syndrome to investigate whether
      combined prenatal and postnatal ethanol exposure affects met-enkephalin levels in
      the brains of male and female Long-Evans adult rats. Intragastric ethanol was
      administered to a group of rats (ET) from gestational day (GD) 1 through 22 and
      from postnatal day (PD) 2 through 10. The control groups consisted of a
      nontreated control group (NTC) and an intubated control group (IC) that received
      the intragastric intubation procedure but no exposure to ethanol. We measured met
      enkephalin levels in the prefrontal cortex, nucleus accumbens, hypothalamus,
      central and basolateral nucleus of amygdala and ventral tegmental area. Met
      enkephalin levels in the hypothalamus of male and female ET animals were
      significantly higher than those in either the NTC or IC animals. Met-enkephalin
      levels in the central nucleus of the amygdala of male and female ET animals were
      significantly lower than the levels in the NTC animals. Met-enkephalin levels in
      the nucleus accumbens of ET females were significantly greater than those in the
      IC females. These results demonstrate that the combination of prenatal and
      postnatal ethanol exposure affects basal met-enkephalin levels in specific
      regions in a sex-specific manner. These changes in met-enkephalin levels may
      explain how early ethanol exposure affects opioid-regulated behaviors such as
      social play, sexual behavior, and other social behaviors.

PMID- 16457987
TI  - Ultrastructural evaluation of 585-nm pulsed-dye laser-treated glottal dysplasia.
AB  - OBJECTIVE/HYPOTHESIS: To describe the ultrastructural changes occurring within
      pulsed-dye laser (PDL)-treated glottal tissues. STUDY DESIGN: Prospective.
      METHODS: Nine patients presenting with glottal dysplasia requiring biopsy to rule
      out microinvasive carcinoma were enrolled in this prospective study. At least two
      samples were obtained in each case: one from a PDL-treated area and another from
      a non-PDL-treated area (obtained from a nonphonatory region as an internal
      control). In some cases, a third sample was obtained from the junction between
      PDL- and non-PDL-treated areas. All samples were examined with light microscopy
      (H and E stain) and transmission electron microscopy. Observations were made of
      morphological changes within the epithelium, epithelial/ superficial lamina
      propria (SLP) junction, and the lamina propria of tissues treated with the PDL.
      Eight of nine patients were followed for a period of 9-25 months (mean, 18
      months) with two recurrences that were retreated with awake-PDL and followed for
      an additional 8.3 and 9.5 months without recurrence. Vocal fold appearance
      returned to normal within 3-4 weeks posttreatment. RESULTS: Intraepithelial
      desmosome junctions were preferentially destroyed, and regional blood vessels
      were coagulated. The PDL consistently caused a separation of epithelial cells
      away from the basement membrane. CONCLUSIONS: The PDL allowed for both a surgical
      and a nonsurgical multimodality method for treatment of precancerous lesions with
      minimal effects on the SLP.

PMID- 16457988
TI  - Malnutrition is prevalent in hospitalized medical patients: are housestaff
      identifying the malnourished patient?
AB  - OBJECTIVE: Malnutrition is highly prevalent in hospitalized patients and is often
      not identified by the medical staff. Clinical nutrition and nutritional
      assessment are often neglected components of the curriculum of medical schools.
      The effect of instruction of nutritional assessment early in medical school on
      nutritional practice in clinical training is unknown. Four years after the
      introduction of nutritional assessment in the medical school curriculum, we
      assessed the knowledge of medical students and residents of nutritional
      assessment and the practice of this clinical skill in hospitalized medical
      patients. METHODS: We determined the nutritional status of 69 patients on a
      general medical ward within 10 d of their hospital admission. Hospital records
      were reviewed to determine the documentation of nutrition-related issues and
      practices. A questionnaire was then administered to the housestaff to determine
      their knowledge of assessment of nutritional status. RESULTS: Significant
      malnutrition was found in 69% of patients. Only one patient was identified as
      being malnourished by the housestaff. References to nutritional status were
      recorded in two patient charts. History of weight loss, appetite status, current
      oral intake, and functional status were recorded for fewer than 33% of patients.
      Although measurements of visceral protein stores (albumin and prealbumin) did not
      correlate with nutritional status, medical students and residents considered
      these to be the best markers of nutritional status. CONCLUSIONS: Malnutrition is
      common in hospitalized patients. Instruction of second-year medical students in
      assessment of nutritional status does not result in improved knowledge or
      practice of nutritional assessment in the clinical training years as medical
      housestaff. Additional instruction in nutritional assessment during clinical
      training needs to be emphasized. Hospitals need to develop standardized protocols
      for assessment of nutritional status.

PMID- 16457989
TI  - Effects of simultaneous intakes of indigestible dextrin and diacylglycerol on
      lipid profiles in rats fed cholesterol diets.
AB  - OBJECTIVE: Indigestible dextrin (IDex) and diacylglycerol (DG) are food
      components with physiologic effects on lipid metabolism. Because simultaneous
      intake of dietary components with similar physiologic functions may produce a
      beneficial decrease in risk factors for lifestyle-related diseases, we
      investigated the physiologic effects of simultaneous IDex and DG intake. METHODS:
      Five-week-old male Wistar rats were fed a cholesterol-containing diet with IDex
      and DG (separately and combined) for 28 d. RESULTS: IDex significantly decreased
      serum triacylglycerol concentration and increased the length of small intestinal
      villi, whereas DG produced significant decreases in serum high-density
      lipoprotein cholesterol concentration and significant increases in liver
      cholesterol and triacylglycerol concentrations. CONCLUSIONS: IDex intake
      characteristically decreased serum triacylglycerol concentrations, although no
      additive or synergistic interaction between DG and IDex was observed. These
      results indicate that simultaneous intake of food components with similar
      physiologic functions do not necessarily produce additive or synergistic
      physiologic benefits.

PMID- 16457990
TI  - Association between the prevalence of obesity and adherence to the Mediterranean
      diet: the ATTICA study.
AB  - OBJECTIVE: We evaluated the prevalence of obesity in relation to adherence to a
      Mediterranean diet. METHODS: We conducted a cross-sectional survey that randomly
      enrolled 1514 men (18 to 87 y old) and 1528 women (18 to 89 y old) with no
      history of cardiovascular disease. Anthropometric indices were measured and
      frequency of various foods consumed during a usual week was recorded. Adherence
      to a Mediterranean diet was assessed by a diet score that incorporated the
      inherent characteristics of this diet. RESULTS: Prevalences of overweight and
      obesity were 53% and 20% in men and 31% and 15% in women. An inverse relation was
      observed between diet score, waist-to-hip ratio (r = -0.31, P < 0.001), and body
      mass index (r = -0.4, P < 0.001) after adjusting for sex and age. Greater
      adherence to the Mediterranean diet (i.e., highest tertile) was associated with a
      51% lower odds of being obese (odds ratio 0.49, 95% confidence interval 0.42 to
      0.56) and a 59% lower odds of having central obesity (odds ratio 0.41, 95%
      confidence 0.35 to 0.47) compared with a non-Mediterranean diet (i.e., lowest
      tertile) after controlling for age, sex, physical activity status, metabolism,
      and other variables. CONCLUSION: We observed an inverse relation between
      adherence to a Mediterranean dietary pattern and prevalence of obesity in a free
      eating, population-based sample of men and women, irrespective of various
      potential confounders.

PMID- 16457991
TI  - Inhibition of fatty acid beta-oxidation attenuates the reinforcing effects and
      palatability to fat.
AB  - OBJECTIVE: We investigated the effects of the energy signal on the reinforcing
      effects and palatability to fat in mice. METHODS: To examine the effects of
      postingestive energy signal, mice were injected with 400 micromol/kg body mass of
      mercaptoacetate, a beta-oxidation blocker or with saline (control group).
      Reinforcing effects and palatability response were examined with the conditioned
      place preference and one-bottle tests, respectively. RESULTS: In conditioned
      place preference tests, the mercaptoacetate group exhibited reinforcing effects
      when offered a 40% sucrose solution, which is not metabolized by the beta
      oxidation pathway, but not when offered 100% corn oil. The control group
      exhibited reinforcing effects when offered the sucrose solution and when offered
      corn oil. In one-bottle tests, the control group exhibited palatability to corn
      oil, but the mercaptoacetate group did not. Consumption of sucrose solution was
      identical for both groups. CONCLUSIONS: These results suggest that postingestive
      energy signal influences the reinforcing effects and palatability of fat.

PMID- 16457993
TI  - Emerging roles of chloride channels in human diseases.
AB  - In the past decade, there has been remarkable progress in understanding of the
      roles of Cl(-) channels in the development of human diseases. Genetic studies in
      humans have identified mutations in the genes encoding Cl(-) channels which lead
      to a loss of Cl(-) channel activity. These mutations are responsible for the
      development of a variety of deleterious diseases in muscle, kidney, bone and
      brain including myotonia congenita, dystrophia myotonica, cystic fibrosis,
      osteopetrosis and epilepsy. Recent studies indicate that some diseases may
      develop as a result of Cl(-) channel activation. There is growing evidence that
      the progression of glioma in the brain and the growth of the malaria parasite in
      red blood cells may be mediated through Cl(-) channel activation. These findings
      suggest that Cl(-) channels may be novel targets for the pharmacological
      treatment of a broad spectrum of diseases. This review discusses the proposed
      roles of abnormal Cl(-) channel activity in the pathogenesis of human diseases.

PMID- 16457995
TI  - Limited interaction between tacrolimus and P-glycoprotein in the rat small
      intestine.
AB  - The significance of intestinal P-glycoprotein (P-gp) in determining the oral
      bioavailability of tacrolimus has been still controversial. In this study, we
      reevaluated the interaction of tacrolimus with P-gp in the rat small intestine,
      by evaluating its absorption from the rat small intestine and its modulating
      effect on the absorption of known P-gp substrates (digoxin, methylprednisolone,
      and vinblastine). Intestinal absorption of tacrolimus itself was as extensive as
      other P-gp modulators such as cyclosporine and verapamil. While cyclosporine and
      verapamil significantly increased the absorption of methylprednisolone and
      vinblastine through potent inhibition of intestinal P-gp, tacrolimus failed to
      achieve this. When cyclosporine and tacrolimus were intravenously administered to
      rats, digoxin absorption was significantly increased by cyclosporine but not by
      tacrolimus. When tacrolimus was coadministered with clotrimazole, a specific
      CYP3A inhibitor, into the rat small intestine, the area under the curve of
      tacrolimus blood concentrations increased more than seven-fold compared with that
      of tacrolimus alone. Our present results strongly suggest that the interaction
      between tacrolimus and P-gp is limited in the rat small intestine and that
      extensive metabolism by CYP3A enzymes is more responsible for the low oral
      bioavailability of tacrolimus. It was considered that the extensive absorption of
      cyclosporine and verapamil was closely associated with their potent ability to
      inhibit intestinal P-gp.

PMID- 16457996
TI  - [Ophtalmologic clinical case].

PMID- 16457994
TI  - The homeobox gene irx1a is required for the propagation of the neurogenic waves
      in the zebrafish retina.
AB  - Neurogenesis in the compound eyes of Drosophila and the camera eyes of
      vertebrates spreads in a wave-like fashion. In both phyla, waves of hedgehog
      expression are known to drive the wave of neuronal differentiation. The mechanism
      controlling the propagation of hedgehog expression during retinogenesis of the
      vertebrate eye is poorly understood. The Iroquois homeobox genes play important
      roles in Drosophila eye development; they are required for the up-regulation of
      hedgehog expression during propagation of the morphogenetic furrow. Here, we show
      that the zebrafish Iroquois homolog irx1a is expressed during retinogenesis and
      knockdown of irx1a results in a retinal phenotype strikingly similar to those of
      sonic hedgehog (shh) mutants. Analysis of shh-GFP transgene expression in irx1a
      knockdown retinas revealed that irx1a is required for the propagation of shh
      expression through the retina. Transplantation experiments illustrated that the
      effects of irx1a on shh expression are both cell-autonomous and non-cell
      autonomous. Our results reveal a role for Iroquois genes in controlling hedgehog
      expression during vertebrate retinogenesis.

PMID- 16457992
TI  - Pathological pattern of Mdx mice diaphragm correlates with gradual expression of
      the short utrophin isoform Up71.
AB  - Utrophin gene is transcribed in a large mRNA of 13 kb that codes for a protein of
      395 kDa. It shows amino acid identity with dystrophin of up to 73% and is widely
      expressed in muscle and non-muscle tissues. Up71 is a short utrophin product of
      the utrophin gene with the same cysteine-rich and C-terminal domains as full
      length utrophin (Up395). Using RT-PCR, Western blots analysis, we demonstrated
      that Up71 is overexpressed in the mdx diaphragm, the most pathological muscle in
      dystrophin-deficient mdx mice, compared to wild-type C57BL/10 or other mdx
      skeletal muscles. Subsequently, we demonstrated that this isoform displayed an
      increased expression level up to 12 months, whereas full-length utrophin (Up395)
      decreased. In addition, beta-dystroglycan, the transmembrane glycoprotein that
      anchors the cytoplasmic C-terminal domain of utrophin, showed similar increase
      expression in mdx diaphragm, as opposed to other components of the dystrophin
      associated protein complex (DAPC) such as alpha-dystrobrevin1 and alpha
      sarcoglycan. We demonstrated that Up71 and beta-dystroglycan were progressively
      accumulated along the extrasynaptic region of regenerating clusters in mdx
      diaphragm. Our data provide novel functional insights into the pathological role
      of the Up71 isoform in dystrophinopathies.

PMID- 16457997
TI  - Dietary docosahexaenoic acid alters pregnant rat reproductive tissue
      prostaglandin and matrix metalloproteinase production.
AB  - Shortened gestation is a major cause of infant mortality and morbidity. Evidence
      from both human and animal studies suggests that essential fatty acids of the n-6
      and n-3 series play important and modifiable roles in gestational duration. We
      examined the influence of linolenic acid (LnA) vs. docosahexaenoic acid (DHA) on
      rat reproductive tissue prostaglandin (PG) and matrix metalloproteinase (MMP)
      indices of gestational duration. By varying the oil source of the diet, AIN-93G
      diets were constructed to provide either 0.7 energy % (en%) LnA, the current US
      intake of n-3 fatty acids, or 0.7 en% DHA. In addition, enhanced levels of 2.0
      en% LnA or 2.0 e% DHA diets were also constructed. All diets contained
      approximately 6.0 en% linoleic acid (LA), the current US intake of LA. Four
      groups of 10 female rats were time-mated and fed the respective diets from
      conception through Day 20 of gestation. Day 20 uterus and placenta DHA were
      significantly increased by 160-180% by the 0.7 en% DHA diet, and by 250-350% by
      the 2.0 en% DHA diets in comparison to 0.7 en% LnA diet. DHA diets also
      significantly reduced uterus and placenta arachidonic acid content. Day 20
      placenta and uterus PGE(2) and placenta PGF(2alpha) production rates were
      significantly reduced by 27-47% in the 0.7 en% DHA group in comparison to 0.7 en%
      LnA. Increasing LnA to 2.0 en% was without effect. Providing DHA at the enhanced
      2.0 en% did not significantly enhance the suppression of PG production. Placenta
      active MMP-2 and active MMP-9 (gelatinase) production was suppressed
      significantly by 30-43% in the 0.7 en% DHA group in comparison to the 0.7 en% LnA
      group, and 2.0 en% DHA did not enhance this suppression. Placenta collagenase
      activity comprising the sum of MMP-1, MMP-8 and MMP-13 was also suppressed by 60%
      in the 0.7 en% DHA diet group with no additional effect with 2.0 en% DHA
      provision. These results suggest that substituting DHA for LnA even at the
      current US n-3 fatty acid intake of 0.7 en% is effective in suppressing indices
      of premature delivery and shortened gestation. Increasing LnA intake by 3-fold to
      2.0 en% is not effective. The form of dietary n-3 fatty acid, DHA vs. LnA,
      appears to be more important than the amount.

PMID- 16457998
TI  - Lithographic techniques and surface chemistries for the fabrication of PEG
      passivated protein microarrays.
AB  - This article presents a new technique to fabricate patterns of functional
      molecules surrounded by a coating of the inert poly(ethylene glycol) (PEG) on
      glass slides for applications in protein microarray technology. The chief
      advantages of this technique are that it is based entirely on standard
      lithography processes, makes use of glass slides employing surface chemistries
      that are standard in the microarray community, and has the potential to massively
      scale up the density of microarray spots. It is shown that proteins and
      antibodies can be made to self-assemble on the functional patterns in a
      microarray format, with the PEG coating acting as an effective passivating agent
      to prevent non-specific protein adsorption. Various standard surface chemistries
      such as aldehyde, epoxy and amine are explored for the functional layer, and it
      is conclusively demonstrated that only an amine-terminated surface satisfies all
      the process constraints imposed by the lithography process sequence. The
      effectiveness of this microarray technology is demonstrated by patterning
      fluorescent streptavidin and a fluorescent secondary antibody using the well
      known and highly specific interaction between biotin and streptavidin.

PMID- 16457999
TI  - Utilization of meat industry by products: protein hydrolysate from sheep visceral
      mass.
AB  - Protein hydrolysate was prepared from pre-treated sheep visceral mass (including
      stomach, large and small intestines) by enzymatic treatment at 43+/-1 degrees C
      (at the in situ pH 7.1+/-0.2 of the visceral mass) using fungal protease. The
      enzyme readily solubilized the proteins of the visceral mass as indicated by the
      degree of hydrolysis (34%) and nitrogen recovery (>64%). Hydrolysis with an
      enzyme level of 1% (w/w of total solids) at 43+/-1 degrees C with a pH around 7.0
      for 45 min was found to be the optimum condition. The yield of protein
      hydrolysate was about 6% (w/w). The amino acid composition of the protein
      hydrolysate that was very hygroscopic, was comparable to that of casein.

PMID- 16458000
TI  - The lethality of Euphorbia conspicua to adults of Biomphalaria glabrata, cercaria
      of Schistosoma mansoni and larvae of Artemia salina.
AB  - Leaf extracts of Euphorbia conspicua (Euphorbiaceae), together with the latex and
      fractions derived therefrom, were evaluated for their molluscicidal and
      cercaricidal activities and their toxicities to brine shrimps. Whilst the leaf
      extracts were inactive against Biomphalaria glabrata, the latex, its triterpenic
      fraction and irritant fractions I and II exhibited high activities against adult
      snails with LC90 values of 4.87, 10.55, 0.64 and 0.10 microg/mL, respectively.
      The latex and its derived fractions were considered lethal to the cercaria of
      Schistosoma mansoni at concentrations of 100 microg/mL. The toxicities of the
      latex and the irritant fractions, but not of the triterpenic fraction, against
      Artemia salina were high with LC50 values < 10 microg/mL. The possible
      application of the latex of E. conspicua as an alternative natural molluscicide
      is considered.

PMID- 16458001
TI  - Production of penicillic acid by Aspergillus sclerotiorum CGF.
AB  - The production of penicillic acid by Aspergillus sclerotiorum CGF for the
      biocontrol of Phytophthora disease was investigated in submerged fermentation
      using media composed of different nutrients. Soluble starch was found to be the
      most effective substrate among the carbon sources used, and produced the highest
      penicillic acid concentration of 2.98 mg ml(-1). When organic nitrogen sources
      were used, pharmamedia, yeast extract, and polypeptone-S were found to be
      suitable organic nitrogen sources (2.46-2.71 mg ml(-1)). The production of
      penicillic acid was not detected in when inorganic nitrogen sources were used.
      Only Na2HPO4, among the metal ions and phosphate salts tested, increased the
      production of penicillic acid (approximately 20%). When A. sclerotiorum CGF was
      cultured in optimal medium [8.0% (w/v) soluble starch, 0.6% (w/v) yeast extract,
      and 0.3% (w/v) Na2HPO4], maximum penicillic acid concentration (approximately
      9.40 mg ml(-1)) and cell mass (approximately 17.4 g l(-1)) were obtained after 12
      days.

PMID- 16458002
TI  - Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and
      isoglobotrihexosylceramide (iGb3).
AB  - Glycoceramides can activate NKT cells by binding with CD1d to produce IFN-gamma,
      IL-4, and other cytokines. An efficient synthetic pathway for alpha
      galactosylceramide (KRN7000) was established by coupling a protected galactose
      donor to a properly protected ceramide. During the investigation, it was
      discovered that when the ceramide was protected with benzyl groups, only beta
      galactosylceramide was produced from the glycosylation reaction. In contrast, the
      ceramide with benzoyl protecting groups produced alpha-galactosylceramide.
      Isoglobotrihexosylceramide (iGb3) was prepared by glycosylation of Galalpha1
      3Galbeta1-4Glc donor with 2-azido-sphingosine in high yield. Biological assays on
      the synthetic KRN7000 and iGb3 were performed using human and murine iNKT cell
      clones or hybridomas.

PMID- 16458003
TI  - QSAR study on topically acting sulfonamides incorporating GABA moieties: a
      molecular connectivity approach.
AB  - A quantitative Structure-activity relationship study (QSAR) on a set of carbonic
      anhydrase (CA, EC 4.2.1.1) inhibitors is reported using first-order valence
      connectivity index ((1)chi(v)). The inhibitory activity against three isozymes
      CAI, CAII (cystolic forms), and CAIV (membrane bound form), some of which are
      involved in important physiological processes, were considered for this purpose.
      All the three activities were excellently modeled by (1)chi(v) in multi
      parametric regression containing indicator parameters. The results are critically
      discussed on the basis of various regression parameters.

PMID- 16458005
TI  - Chromatin regulation of virus infection.
AB  - Cellular chromatin forms a dynamic structure that maintains the stability and
      accessibility of the host DNA genome. Viruses that enter and persist in the
      nucleus must, therefore, contend with the forces that drive chromatin formation
      and regulate chromatin structure. In some cases, cellular chromatin inhibits
      viral gene expression and replication by suppressing DNA accessibility. In other
      cases, cellular chromatin provides essential structure and organization to the
      viral genome and is necessary for successful completion of the viral life cycle.
      Consequently, viruses have acquired numerous mechanisms to manipulate cellular
      chromatin to ensure viral genome survival and propagation.

PMID- 16458006
TI  - Letter to the editor.

PMID- 16458004
TI  - Polyhydroxylated 4-thiaflavans as multipotent antioxidants: protective effect on
      oxidative DNA damage in vitro.
AB  - Hydroxylated 4-thiaflavans, possessing the antioxidant features of catechol
      containing flavonoids and/or tocopherols, were evaluated as protective agents
      against oxidation damage induced in herring sperm DNA by cumene hydroperoxide
      (CumOOH) or by the glutathione/ferric ion (GSH/Fe(3+)) system. Our data indicate
      that the effective protection exerted by some of the tested compounds is overall
      higher than those provided by catechin and alpha-tocopherol, which might be
      attributed both to the scavenging properties and chelation of Fe(2+) ions.

PMID- 16458007
TI  - Synthesis of 7-oxo-7H-naphtho[1,2,3-de]quinoline derivatives as potential
      anticancer agents active on multidrug resistant cell lines.
AB  - Following our earlier finding that tetracyclic anthraquinone analogs with a fused
      pyridone ring exhibit cytotoxic activity toward multidrug resistant tumor cells,
      a series of new potential antitumor agents, 7-oxo-7H-naphtho[1,2,3-de]quinoline
      derivatives (3, 6-8, 10-12, 14, 15, and 18), bearing one or two basic side chains
      and various substituents at the pyridone ring, have been synthesized. The
      compounds have been obtained from 1-amino-4-chloroanthraquinone or 1
      aminoanthraquinone by cyclization with diethyl malonate and the subsequent
      reactions of the key intermediates 2, 4, and 17. The compounds exhibited
      cytotoxic activity toward sensitive human leukemia cell line HL-60 and against
      its resistant sublines HL-60/VINC (MDR1 type) and HL-60/DX (MRP1 type).

PMID- 16458009
TI  - Synthesis and biological activity of tricyclic analogues of 9-[[cis-1',2'
      bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine.
AB  - The base moiety of the potent antiherpetic agent 9-[[cis-1',2'
      bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine 3 was transformed into that of
      the tricyclic 3,9-dihydro-9-oxo-6-R-5H-imidazo[1,2-a]purine system. The tricyclic
      analogues 5a-d were evaluated for their activity against herpes viruses as well
      as for cytostatic activity against HSV-1 thymidine kinase (TK) gene-transduced
      human osteosarcoma tumor cells. Marked activity was found against VZV. The 6
      phenyl-substituted fluorescent analogues 5c and d were comparable to that of
      parent 3 in activity against the VZV strain YS and were 3-fold less active
      against the VZV strain OKA. The compounds 5a-d also showed marked activity
      against HSV-1 (KOS) and HSV-2 (G)-against the former generally approximately
      comparable to that of acyclovir 1a and one order of magnitude lower than 3;
      against the latter comparable to that of 1a and approximately 6- to 30-fold lower
      than that of 3. The most pronounced cytostatic activity (5-fold lower than that
      of 3) was exhibited by compounds 5c and d. Tricyclic analogues with pseudosugar
      moieties are intrinsically bio-active.

PMID- 16458008
TI  - Essential structural profile of a dual functional inhibitor against
      cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and 3D
      QSAR analyses on DHDMBF analogues.
AB  - It is recently proposed that compounds with equal capabilities of inhibiting COX
      and 5-LOX, both are key enzymes involved in the arachidonic acid (AA) cascade,
      are expected to be safer non-steroidal anti-inflammatory drugs (NSAIDs). To dig
      out helpful information in designing dual functional inhibitors against the two
      enzymes, homology modeling, molecular dynamics (MD) simulations, automated
      docking, and 3D-QSAR analyses were performed in this study on 21 COX-2/5-LOX dual
      inhibitors, namely, 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran (DHDMBF)
      analogues. A 3D-model of 5-LOX was built based on the high-resolution X-ray
      structure of rabbit reticulocyte 15-lipoxygenase. Molecular docking was then
      applied to locate the binding orientations and conformations of DHDMBF analogues
      with COX-2 and 5-LOX, respectively, leading to highly predictive CoMFA models
      constructed on the basis of the binding conformations with q2 values of 0.782 and
      0.634 for COX-2 and 5-LOX, respectively. In addition, CoMFA field distributions
      were found in good agreement with the structural characteristics of the
      corresponding binding sites. Both the docking simulations and QSAR analyses
      suggest that new potent dual inhibitors should share a structural feature with a
      moderately bulky group at R2 position and a rather negatively charged group
      around the position of the carbonyl group of DHDMBFs. Therefore, the final 3D
      QSAR models and the information of the inhibitor-enzyme interaction should be
      useful in developing new NSAIDs as anti-inflammation drugs with favorable safety
      profile.

PMID- 16458012
TI  - Surface modification of mica due to titanium sputtering as studied by positron
      annihilation.
AB  - Study was conducted of surface structural modification of layered sheets of mica
      that had been subjected to titanium (Ti) sputter coating, use being made of a
      variable but mono energetic slow positron beam. Comparison has been drawn with
      the structure of pure muscovite mica sheet. Doppler broadening (DB) of the energy
      of annihilation radiation has been used as a parameter to assay changes in the
      surface characteristics within a depth profile of 500 angstroms. In support of
      these investigations, X-ray reflectivity data was used to assay titanium film
      thickness and the electron density profile of the film on mica. Finally, changes
      involving the surface micro-morphology of the system have been corroborated by
      scanning electron microscopy.

PMID- 16458010
TI  - Norbornyllactone-substituted xanthines as adenosine A(1) receptor antagonists.
AB  - During the search for second-generation adenosine A(1) receptor antagonist
      alternatives to the clinical candidate 8-(3-oxa-tricyclo[3.2.1.0(2,4)]oct-6-yl)
      1,3-dipropyl-3,7-dihydro-purine-2,6-dione (BG9719), we developed a series of
      novel xanthines substituted with norbornyl-lactones that possessed high binding
      affinities for adenosine A(1) receptors and in vivo activity.

PMID- 16458011
TI  - Bis-imidazoles as molecular probes for peripheral sites of the zinc endopeptidase
      of botulinum neurotoxin serotype A.
AB  - Botulinum neurotoxin serotype A (BoNTA) is highly toxic, and its antidote is
      currently unavailable. The essential light-chain subunit of BoNTA is a zinc
      endopeptidase that can be used as a target for developing antidotes. However, the
      development of high-affinity, small-molecule inhibitors of the endopeptidase is
      as challenging as the development of small-molecule inhibitors of protein-protein
      complexation. This is because the polypeptide substrate wraps around the
      circumference of the endopeptidase upon binding, thereby constituting an
      unusually large substrate-enzyme interface of 4840 angstroms2. To overcome the
      large-interface problem, we propose using the zinc-coordination and bivalence
      approaches to design inhibitors of BoNTA. Here we report the development of
      alkylene-linked bis-imidazoles that inhibit the endopeptidase in a two-site
      binding mode. The bis-imidazole tethered with 13 methylene groups, the most
      potent of the alkylene-linked dimers, showed 61% inhibition of the zinc
      endopeptidase of BoNTA at a concentration of 100 microM. The results demonstrate
      the presence of a peripheral binding site for an imidazolium group at the rim of
      the BoNTA active-site cleft. This peripheral site enables the use of the
      bivalence approach to improve our previously reported small-molecule inhibitors
      that were developed according to the zinc-coordination approach.

PMID- 16458013
TI  - 2-[(R-phenyl)amine]-1,4-naphthalendiones as photosystem I electron acceptors:
      structure-activity relationship of m- and p-PAN compounds with QSAR analysis.
AB  - Nineteen 2-[(R-phenyl)amine]-1,4-naphthalendione derivatives (PAN) were tested on
      spinach thylakoids for their activity as electron acceptors. These molecules act
      as photosystem I electron acceptors in the micromolar range. AC(50) values varied
      from 5 nM to 24 microM. QSAR analysis revealed a linear correlation of the m-PAN
      derivative log [1/AC(50)] with the energy difference of the LUMO and HOMO
      orbitals. The biological activity of p-PAN derivatives correlates linearly with
      structural parameters. Electron affinity is being the most important. The half
      wave I potential values (E(1/2)) of PAN compounds (from -213 to -569 mV vs. NHE)
      match with the mid-point potentials of the A(0) to F(X) niche of PSI electron
      transport carriers. The logP values of PAN derivatives were 3.35 and 3.88,
      indicating that they are hydrophobic compounds. Therefore PAN compounds accept
      electrons at the hydrophobic A(0) to F(X) niche of PSI.

PMID- 16458014
TI  - Apoptosis, necrosis and cell proliferation-inhibition by cyclosporine A in U937
      cells (a human monocytic cell line).
AB  - The immunosuppressive drug cyclosporine A (CsA) has been used in both organ
      transplantation and the treatment of autoimmune disorders. However, the drug
      causes adverse effects in the kidney, liver and nervous system, characterized by
      cellular loss in the affected area. Apoptosis has been shown to play a role in
      CsA-induced cytotoxicity. Because permeabilization of the mitochondrial membrane
      is a common criterion in most apoptotic settings in vertebrate cells, here we
      evaluated whether CsA causes loss of mitochondrial function in the pathway
      leading to cellular cytotoxicity. We found that CsA caused a concentration- and
      time-dependent loss of cell viability in the U937 cell line. Treatment of cells
      at a dose of 10 microM CsA resulted in G0/G1 arrest with a concurrent decrease in
      the number of cells in the S and G2/M phases of the cell cycle. In mechanistic
      studies related to the loss of viability, treating cells with 10 microM CsA for
      24 h resulted in both DNA fragmentation and an increase of annexin-V-positive
      cells. CsA treatment also increased activity of the cysteine protease caspase-3,
      decreased the mitochondrial membrane potential and induced the release of
      cytochrome c into the cytosol. Furthermore, CsA treatment increased the number of
      cells in the sub-G0/G1 peak, indicative of a reduction in DNA, although this
      increase was not observed when cells were pre-treated with a broad caspase
      inhibitor. In the study, we also found that a higher dose of CsA induces LDH
      release when the cells were incubated for a longer period. Taken together, these
      data suggest that the mode of cell death induced by CsA is dose- and time
      dependent. Short-term incubation with lower doses of CsA arrests cell growth;
      this arrest overlaps with the occurrence of apoptosis and then with necrosis
      after longer treatment periods with higher doses of CsA.

PMID- 16458015
TI  - Clinical application of expanded CD4+25+ cells.
AB  - A central goal immunologists has been to develop targeted therapies that will
      induce or maintain immunologic tolerance in the absence of potentially harmful
      immunosuppression. The ability to isolate and expand regulatory T-cell
      populations with immune suppressive activity will enable new forms of adoptive
      immunotherapy that may achieve this long held dream. Assuming that certain
      technical challenges regarding the manufacturing of regulatory T cells can be
      overcome, a wide variety of clinical applications can be envisioned using
      adoptively transferred CD4(+)CD25(+) regulatory T cells. It is likely that
      suppressor T cells will first be tested for their ability to prevent or treat
      graft-versus-host disease (GVHD) following allogeneic bone marrow or stem cell
      transplantation. A related approach will be clinical studies to induce allogeneic
      or xenogeneic tolerance using regulatory T cells in solid organ transplantation.
      A more technically challenging approach will be the use of regulatory T-cell
      therapy for autoimmune disorders. Finally on the horizon are approaches that will
      use genetically engineered lymphocytes to replace regulatory T cells in the
      immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome,
      and potentially to create more potent regulatory T (Treg) cells with enhanced
      suppressive activity.

PMID- 16458017
TI  - A computerized apparatus designed to automatically dispense, measure, and record
      alcohol consumption by individual members of a rhesus macaque social group: trait
      like drinking across social- and single-cage conditions.
AB  - BACKGROUND: The present study tested the validity of an automated ethanol
      dispensing apparatus that is capable of identifying individual monkeys and
      precisely measuring their levels of ethanol consumption while living in a social
      group, and assessed individual subjects' level of consumption when alone and in
      social groups. METHODS: In Experiment 1, 21 rhesus macaques (Macaca mulatta) were
      given access for 1-h each day to the dispensing apparatus, which contained an
      aspartame-sweetened 8.4% (v/v) ethanol solution. Measurements of blood ethanol
      concentrations were taken for each subject and compared with the level of
      consumption recorded by the apparatus for those subjects. To examine the
      possibility that competition among the animals limited their access to the
      dispensing unit, in Experiment 2, 10 of the subjects used in Experiment 1 were
      singly housed to allow them to drink without interference from other monkeys. A
      correlation was then performed to assess the interindividual relationship between
      the amount of ethanol consumed in these two housing conditions. RESULTS: In
      Experiment 1, the volume of solution measured and recorded by the apparatus
      correlated positively with the true volume dispensed. Furthermore, the volume of
      solution reported by the computer to have been consumed by an individual subject
      correlated positively with blood ethanol concentrations. In Experiment 2, the
      volume of ethanol consumed by individual subjects in single cages correlated
      positively with their consumption in the social group. CONCLUSIONS: The apparatus
      accurately identified and measured individual patterns of ethanol consumption
      among socially housed animals. Additionally, individual differences in ethanol
      consumption remained stable across settings, as shown by the strong positive
      correlation between drinking in a social setting versus drinking alone. This
      finding may thus reflect an individual's constitutional proclivity to consume
      alcohol.

PMID- 16458016
TI  - Calcium-dependent expression of TNF-alpha in neural cells is mediated by the
      calcineurin/NFAT pathway.
AB  - We report induction of TNF-alpha via the calcium/calcineurin/NFAT pathway in PC12
      neural cells. In PC12, expression of TNF-alpha mRNA, protein and TNF-alpha gene
      promoter activity was induced by co-stimulation with phorbol ester and either
      calcium ionophore A23187 or the L-type Voltage Gated Calcium Channel agonist Bay
      K 8644. Pre-treatment with calcineurin inhibitors CsA or FK506 inhibited the
      dominant calcium-dependent component of this induction, limiting it to the level
      achieved with phorbol ester alone. Promoter activation by Bay was abolished by
      nifedipine, a specific inhibitor of L-type Voltage Gated Calcium Channels.
      Exogenous NFAT protein transactivated the TNF-alpha promoter, and the peptide
      VIVIT-a specific inhibitor of calcineurin/NFAT binding-blocked calcium-inducible
      transactivation of the TNF-alpha promoter. Given proposed functions of TNF-alpha
      in spatial learning, memory and the pathogenesis of neurodegenerative diseases,
      the data presented suggest an important role for calcineurin/NFAT signaling in
      these key neurological processes.

PMID- 16458018
TI  - Studying primate learning in group contexts: Tests of social foraging, response
      to novelty, and cooperative problem solving.
AB  - Learning commonly refers to the modification of behavior through experience,
      whereby an animal gains information about stimulus-response contingencies from
      interacting with its physical environment. Social learning, on the other hand,
      occurs when the same information originates, not from the animal's personal
      experience, but from the actions of others. Socially biased learning is the
      'collective outcome of interacting physical, social, and individual factors' [D.
      Fragaszy, E. Visalberghi, Learn. Behav. 32 (2004) 24-35.] (see p. 24). Mounting
      interest in animal social learning has brought with it certain innovations in
      animal testing procedures. Variants of the observer-demonstrator and cooperation
      paradigms, for instance, have been used widely in captive settings to examine the
      transmission or coordination of behavior, respectively, between two animals.
      Relatively few studies, however, have examined social learning in more complex
      group settings and even fewer have manipulated the social environment to
      empirically test the effect of group dynamics on problem solving. The present
      paper outlines procedures for group testing captive non-human primates, in
      spacious arenas, to evaluate the social modulation of learning and performance.
      These methods are illustrated in the context of (1) naturalistic social foraging
      problems, modeled after traditional visual discrimination paradigms, (2) response
      to novel objects and novel extractive foraging tasks, and (3) cooperative problem
      solving. Each example showcases the benefits of experimentally manipulating
      social context to compare an animal's performance in intact groups (or even
      pairs) against its performance under different social circumstances. Broader
      application of group testing procedures and manipulation of group composition
      promise to provide meaningful insight into socially biased learning.

PMID- 16458019
TI  - In vivo formation steps of the hard alpha-keratin intermediate filament along a
      hair follicle: evidence for structural polymorphism.
AB  - Several aspects of the intermediate filaments' molecular architecture remain
      mysterious despite decades of study. The growth process and the final
      architecture may depend on the physical, chemical, and biochemical environment.
      Aiming at clarifying this issue, we have revisited the structure of the human
      hair follicle by means of X-ray microdiffraction. We conclude that the histology
      based growth zones along the follicle are correlated to the fine architecture of
      the filaments deduced from X-ray microdiffraction. Our analysis reveals the
      existence of two major polymorph intermediate filament architectures. Just above
      the bulb, the filaments are characterized by a diameter of 100 Angstroms and a
      low-density core. The following zone upwards is characterized by the lateral
      aggregation of the filaments into a compact network of filaments, by a
      contraction of their diameter (to 75 Angstroms) and by the setting up of a long
      range longitudinal ordering. In the upper zone, the small structural change
      associated with the tissue hardening likely concerns the terminal domains. The
      architecture of the intermediate filament in the upper zones could be specific to
      hard alpha-keratin whilst the other architecture found in the lower zone could be
      representative for intermediate filaments in a different environment.

PMID- 16458021
TI  - Capsid-like arrays in crystals of chimpanzee adenovirus hexon.
AB  - The major coat protein, hexon, from a chimpanzee adenovirus (AdC68) is of
      interest as a target for vaccine vector modification. AdC68 hexon has been
      crystallized in the orthorhombic space group C222 with unit cell dimensions of a
      = 90.8 A, b = 433.0 A, c = 159.3 A, and one trimer (3 x 104,942 Da) in the
      asymmetric unit. The crystals diffract to 2.1 A resolution. Initial studies
      reveal that the molecular arrangement is quite unlike that in hexon crystals for
      human adenovirus. In the AdC68 crystals, hexon trimers are parallel and pack
      closely in two-dimensional continuous arrays similar to those formed on electron
      microscope grids. The AdC68 crystals are the first in which adenovirus hexon has
      molecular interactions that mimic those used in constructing the viral capsid.

PMID- 16458020
TI  - Domains of Importin-alpha2 required for ring canal assembly during Drosophila
      oogenesis.
AB  - Null-mutation in Drosophila importin-alpha2, such as the deficiency imp
      alpha2(D14), causes recessive female sterility with the formation of dumpless
      eggs. In imp-alpha2(D14) the transfer of nurse cell components to the oocyte is
      interrupted and the Kelch protein, an oligomeric ring canal actin organizer, is
      normally produced but fails to associate with the ring canals resulting in their
      occlusion. To define domains regulating Kelch deposition on ring canals we
      performed site-directed mutagenesis on protein binding domains and putative
      phosphorylation sites of Imp-alpha2. Phenotypic analysis of the mutant transgenes
      in imp-alpha2(D14) revealed that mutations affecting the Imp-beta binding-domain,
      the dimerization domain, and specific serine residues of putative phosphorylation
      sites led to a normal or nearly normal oogenesis but arrested early embryonic
      development, whereas mutations in the nuclear localization signal (NLS) and
      CAS/exportin binding domains resulted in ring canal occlusion and a drastic
      nuclear accumulation of the mutant proteins. Deletion of the Imp-beta binding
      domain also gave rise to a nuclear localization of the mutant protein, which
      partially retained its function in ring canal assembly. Thus, we propose that
      mutations in NLS and CAS binding domains affect the deposition of Kelch onto the
      ring canals and prevent the association of Imp-alpha2 with a negative regulator
      of Kelch function.

PMID- 16458022
TI  - Muscles within muscles: Coordination of 19 muscle segments within three shoulder
      muscles during isometric motor tasks.
AB  - The aim of the present study was to determine how the intra-muscular segments of
      three shoulder muscles were coordinated to produce isometric force impulses
      around the shoulder joint and how muscle segment coordination was influenced by
      changes in movement direction, mechanical line of action and moment arm (ma).
      Twenty male subjects (mean age 22 years; range 18-30 years) with no known history
      of shoulder pathologies, volunteered to participate in this experiment. Utilising
      an electromyographic technique, the timing and intensity of contraction within 19
      muscle segments of three superficial shoulder muscles (Pectoralis Major, Deltoid
      and Latissimus Dorsi) were studied and compared during the production of rapid
      (e.g. approximately 400ms time to peak) isometric force impulses in four
      different movement directions of the shoulder joint (flexion, extension,
      abduction and adduction). The results of this investigation have suggested that
      the timing and intensity of each muscle segment's activation was coordinated
      across muscles and influenced by the muscle segment's moment arm and its
      mechanical line of action in relation to the intended direction of shoulder
      movement (e.g. flexion, extension, abduction or adduction). There was also
      evidence that motor unit task groups were formed for individual motor tasks which
      comprise motor units from both adjacent and distant muscles. It was also
      confirmed that for any particular motor task, individual muscle segments can be
      functionally classified as prime mover, synergist or antagonist - classifications
      which are flexible from one movement to the next.

PMID- 16458023
TI  - Surface electromyography as a tool to assess the responses of car passengers to
      lateral accelerations. Part II: Objective comparison of vehicles.
AB  - The purpose of this study was to objectively assess the response of car
      passengers to lateral accelerations. Surface EMG signals were collected
      bilaterally from the cervical erector spinae (CES), latissimus dorsi (LD),
      erector spinae (ES), external oblique (EO), and vastus lateralis (VL) muscles of
      10 subjects. Lateral acceleration was also recorded. Three chassis-seat
      configurations AA, BA and BB were tested, with the first letter denoting the
      chassis and the second the seat. SEMG signals were often contaminated by noise,
      and were, therefore, denoised using the methods explained in part I. Reciprocal
      phasic activity was observed for all muscles except for the EO, and the reaction
      of passengers to lateral accelerations was interpreted as a bust torsion. The RMS
      of EMG segments was used as an indication of muscle activity. Muscle activation
      of VL and ES were significantly affected by the configuration tested (p<0.05),
      with greater activation levels observed for the chassis A than for the chassis B.
      Such a finding implies that greater roll requires greater muscle activity, thus
      resulting in less comfortable vehicles. Therefore, SEMG can be used to provide an
      objective measure of discomfort in passengers subjected to lateral accelerations
      in a car seat.

PMID- 16458024
TI  - Surface electromyography as a tool to assess the responses of car passengers to
      lateral accelerations: Part I. Extraction of relevant muscular activities from
      noisy recordings.
AB  - The aim of this paper is to develop a method to extract relevant activities from
      surface electromyography (SEMG) recordings under difficult experimental
      conditions with a poor signal to noise ratio. High amplitude artifacts, the QRS
      complex, low frequency noise and white noise significantly alter EMG
      characteristics. The CEM algorithm proved to be useful for segmentation of SEMG
      signals into high amplitude artifacts (HAA), phasic activity (PA) and background
      postural activity (BA) classes. This segmentation was performed on signal energy,
      with classes belonging to a chi(2) distribution. Ninety-five percent of HAA
      events and 96.25% of BA events were detected, and the remaining noise was then
      identified using AR modeling, a classification based upon the position of the
      coordinates of the pole of highest module. This method eliminated 91.5% of noise
      and misclassified only 3.3% of EMG events when applied to SEMG recorded on
      passengers subjected to lateral accelerations.

PMID- 16458025
TI  - Induction of transforming growth factor-beta 1 on dentine pulp cells in different
      culture patterns.
AB  - Recent studies have documented that TGF-beta1 takes part in dental pulp tissue
      repair. Moreover, dental pulp cells have the potential to differentiate into
      odontoblast-like cells and produce reparative dentine in this process. However,
      the molecular mechanisms and potential interactions between TGF-beta1 and dental
      pulp cells are not clear due to the complexity of the pulp/dentine
      microenvironment. In this study, we investigated the induction of TGF-beta1 on
      the dental pulp cells in cell culture, tissue culture and three-dimensional
      culture patterns. These results demonstrated that TGF-beta1 significantly
      increased the proliferation of cells and activity of ALPase. Dental pulp cells
      cultured in the presence of TGF-beta1 formed mineralization nodules. In the organ
      culture, dental pulp cells treated with TGF-beta1 differentiated into odontoblast
      like cells and formed a pulp-dentinal complex; and TGF-beta1 significantly
      induced synthesis of dentine relative proteins DSPP, DMP-1. The dental pulp cells
      share some characteristics of the odontoblast, such as a parallel arrangement
      with columnar form and a unilateral cell process. Together, these data indicate
      that TGF-beta1 can make dental pulp cells differentiated into odontoblast-like
      cells and form the pulp-dentinal complex. Moreover, these results suggest that
      TGF-beta1 is an important regulatory factor in odontoblast differentiation during
      tooth development and pulp repair.

PMID- 16458026
TI  - Involvement of caspase-3 pathway in anti-apoptotic action of methionine
      enkephalin on CEM x 174 cells in prolonged infection with simian immunodeficiency
      virus in vitro.
AB  - The roles of methionine enkephalin, as an immunomodulator, on immunodeficiency
      virus-induced apoptosis of lymphocytes during prolonged infection are still
      unclear. In the present study, we evaluated the effects of methionine enkephalin
      on the viability, the profile of cell cycle and apoptosis, as well as the
      expression of apoptosis-related genes in CEM x 174 cells infected with simian
      immunodeficiency virus for 72 h. Our data demonstrated that methionine enkephalin
      maintains the viability of cells during the period of prolonged infection.
      Following co-incubation with the virus, CEM x 174 cells were arrested at S phase,
      with increased mortality as a result of apoptosis. Methionine enkephalin could
      abolish virus-induced over-expression of caspase-3. Taken together all findings,
      we conclude that methionine enkephalin may maintain the viability of SIV-infected
      cells via suppressing the expression of caspase-3, which may have clinical
      implications in opioid peptide therapy for AIDS.

PMID- 16458027
TI  - Modulation of the epithelial barrier by dexamethasone and prolactin in cultured
      Madin-Darby canine kidney (MDCK) cells.
AB  - Glucocorticoids and prolactin (PRL) have a direct effect on the formation and
      maintenance of tight junctions (TJs) in cultured endothelial and mammary gland
      epithelial cells. In this work, we investigated the effect of a synthetic
      glucocorticoid dexamethasone (DEX) and PRL on the paracellular barrier function
      in MDCK renal epithelial cells. DEX (4 microM)+PRL (2 microg/ml) and DEX alone
      increased significantly the transepithelial electrical resistance after chronic
      treatment (4 days) of confluent MDCK monolayers or after 24 h treatment of
      subconfluent monolayers. Immunoblotting and immunocytochemistry revealed no
      changes in the expression and distribution of TJ-associated proteins occludin, ZO
      1 and claudin-1 in confluent monolayers after hormone addition. However, a marked
      increase in junctional content for occludin and ZO-1 with no changes in their
      total expression was observed in subconfluent MDCK monolayers 24 h exposed to DEX
      or DEX+PRL. No change in cell proliferation/growth was detected at subconfluent
      conditions following hormone treatment. An increase in the total number of viable
      cells was observed only in confluent MDCK monolayers after exposure to DEX+PRL
      suggesting that the main effect of these hormones on already established barrier
      may be associated with the inhibition of cell death. In conclusion, our data
      suggest that these hormones (specially dexamethasone) have an effect on TJ
      structure and function only during the formation of MDCK epithelial barrier by
      probably modulating the localization, stability or assembly of TJ proteins to
      membrane sites of intercellular contact.

PMID- 16458029
TI  - Ultrasonographic examination of ocular lesions in farmed halibut.
AB  - This paper describes the use of ultrasound to document ocular abnormalities
      occurring in farmed halibut. A cystic condition of the posterior segment of
      farmed halibut with a number of ocular sequelae has been reported previously.
      Further research to elucidate the aetiology and pathogenesis of this condition
      requires in vivo determination of ocular health over and above that provided by
      ophthalmoscopy alone. Ocular ultrasonography would appear to be an optimal
      technique for evaluating the presence of gas- or fluid-filled cysts in the
      posterior segment and retrobulbar space. The aim of this study was to evaluate
      this technique for investigation of the piscine eye and specifically to define
      the role of ultrasonography to detect gas bubble formation in the choroid of
      farmed halibut, a factor considered central to ocular pathology in many of these
      fish. In particular the study sought to assess the minimum size of halibut in
      which intraocular cystic lesions could be identified by ultrasonography and the
      minimum size of lesion identified by ocular ultrasonography. A second objective
      was to correlate ultrasonographic findings with lesions found at post mortem
      ocular examination. A number of halibut of varying sizes, with and without
      clinically apparent ocular lesions, were subjected to examination under
      anaesthesia. A proportion of these fish were subsequently sacrificed to allow
      post mortem ocular evaluation with the aim of correlating ultrasonographic
      findings with intraocular pathological defects.

PMID- 16458028
TI  - Erythropoiesis in the Rps19 disrupted mouse: Analysis of erythropoietin response
      and biochemical markers for Diamond-Blackfan anemia.
AB  - The human ribosomal protein S19 gene (RPS19) is mutated in approximately 20% of
      patients with Diamond-Blackfan anemia (DBA), a congenital disease with a specific
      defect in erythropoiesis. The clinical expression of DBA is highly variable, and
      subclinical phenotypes may be revealed by elevated erythrocyte deaminase (eADA)
      activity only. In mice, complete loss of Rps19 results in early embryonic
      lethality whereas Rps19+/- mice are viable and without major abnormalities
      including the hematopoietic system. We have performed a detailed analysis of the
      Rps19+/- mice. We estimated the Rps19 levels in hematopoietic tissues and we
      analyzed erythrocyte deaminase activity and globin isoforms which are used as
      markers for DBA. The effect of a disrupted Rps19 allele on a different genetic
      background was investigated as well as the response to erythropoietin (EPO). From
      our results, we argue that the loss of one Rps19 allele in mice is fully
      compensated for at the transcriptional level with preservation of erythropoiesis.

PMID- 16458030
TI  - Optimization of data acquisition for EPR imaging.
AB  - In electron paramagnetic resonance imaging (EPRI), long data acquisition time is
      one of the major problems limiting successful and useful biological EPRI
      experiments. Depending on the configuration (spatial distribution of paramagnetic
      species), information embedded in some objects can be characterized using a
      smaller number of projections, while others may require significantly larger
      number of projections to generate similar results. In order to optimize the
      acquisition process, it is therefore important to acquire a different number of
      projections for different objects. In this paper, a prediction scheme is
      demonstrated that can determine the number of projections required to achieve a
      preset reconstruction quality for a given object. After acquiring first few
      projections, corresponding partially filled k-space is analyzed. The complexity
      of data (to interpolate) in k-space is quantified and used to predict the number
      of required projections. All the projections are acquired using a mean-square
      difference-based adaptive acquisition technique that is also demonstrated in this
      work. The purpose of this non-uniform acquisition is to reduce redundancy in the
      acquired data which in turn decreases the number of projections required for the
      given object. It is also demonstrated that the performance of non-uniform
      acquisition is content dependant, and for certain configurations it may not be as
      effective as uniform acquisition in preserving signal from low intensity regions.
      The prediction scheme along with the non-uniform acquisition is tested using
      computer simulations, imaging of experimental phantoms, and in vivo imaging.
      Results indicate that the proposed method may save up to 50% of acquisition time.
      The techniques in this manuscript are described for 2D spatial imaging but can be
      extended to 3D imaging.

PMID- 16458031
TI  - Muscle function and power output during suction feeding in largemouth bass,
      Micropterus salmoides.
AB  - Muscle power output is thought to limit suction feeding performance, yet muscle
      power output during suction feeding has never been directly measured. In this
      study, epaxial activation and strain, hyoid depression, and intra-oral pressure
      were simultaneously measured during suction feeding in the largemouth bass
      (Micropterus salmoides). A mechanical model of muscle force transmission between
      the neurocranium and oral cavity was used to estimate muscle stress, work, and
      power. The epaxials shortened from rest an average of 9% of their length, with
      the highest efforts producing greater than 20% strain. Onset of shortening was
      simultaneous with or shortly after (< 10 ms) onset of activation. Maximal net
      power for individual fish ranged from 17 to 137 W kg(-1). Muscle power was
      significantly correlated with rectified EMG area (r = 0.80; p < 0.0001). The
      power required for cranial expansion was significantly correlated with epaxial
      power (r = 0.81; p < 0.0001), and the power exponent of this relationship (
      approximately 1 for 3 of the 4 fish) implies that epaxial power accounts for most
      of the power of cranial expansion. The limitations imposed by the kinematic
      requirements and loading environment of suction feeding (short delay between
      activation and strain, maximal stress occurring after shortening, operation at
      lengths shorter than resting length) may prevent maximal muscular power
      production.

PMID- 16458032
TI  - Impaired development of broiler chickens by stress mimicked by corticosterone
      exposure.
AB  - The effects of corticosterone (CORT) administration on the development of
      muscular tissues of broiler chickens (Gallus gallus domesticus) fed with diets
      differing in lipid content were investigated. The experimental chickens were
      given one of two experimental diets: high lipid diet (9.9% crude fat) or control
      diet, from 21 d of age. At 28 d of age, half of the chickens in each dietary
      treatment were exposed to CORT treatment, supplemented with 30 mg CORT/kg diet
      for 12 days, while the other half continued to consume the former diet. The
      zootechnical parameters were recorded at 21, 28, 35 and 39 d, and a blood sample
      was obtained from 8 birds of each group, respectively. The growth performance of
      broiler chickens was significantly depressed by CORT administration, but not by
      dietary treatment. Corticosterone treatment resulted in enhanced energy
      expenditure. The results indicate that the development of breast muscle was more
      susceptible to stress mimicked by CORT administration. The results suggest that
      corticosterone administration enhanced hepatic fatty acid synthesis and resulted
      in the redistribution of energy to abdominal store from peripheral tissues. Diet
      rich in lipid content was favorable to the central fat deposit in stressed
      broiler chickens.

PMID- 16458033
TI  - Absorption of toxic beta-glucosides produced by plants and their effect on tissue
      trehalases from insects.
AB  - Trehalases present in body wall, Malpighian tubules, fat body, midgut and
      haemolymph from Tenebrio molitor (Coleoptera), Musca domestica (Diptera),
      Spodoptera frugiperda and Diatraea saccharalis (Lepidoptera) were assayed in the
      presence and absence of toxic beta-glucosides produced by plants or their
      aglycones. The glucosides used were phlorizin, amygdalin, prunasin and the
      aglycone mandelonitrile. In addition, T. molitor and S. frugiperda trehalases
      were assayed with and without esculin. More than 60% of total trehalase activity
      was found in the midgut of these insects. As a rule, trehalases present in each
      insect were inhibited by at least two of the glucosides. Prunasin was the best
      inhibitor in tissues with highest trehalase activity. S. frugiperda beta
      glucosidases were not able to hydrolyze esculin. Nevertheless, their larval
      midguts absorb the intact glucoside that is recovered from the fat body,
      Malpighian tubules and mainly from haemolymph. Mature larvae fed on a diet
      containing 3 mM (0.1%) esculin have 0.2 mM esculin in their haemolymph, and weigh
      60% of control larvae. In vitro, haemolymph trehalase activity is abolished by
      0.5 mM esculin. This inhibition may play a role in the decrease of body weight
      and in animal survival. S. frugiperda larvae reared in 0.1% amygdalin-containing
      diet present higher trehalase activity in tissues than the larvae reared in 0.1%
      esculin-containing diet. Higher trehalase activity should be the reason why the
      S. frugiperda development is not impaired by 1% dietary amygdalin, in contrast to
      what is observed when insects are reared in 0.1% esculin. The data suggest that
      many plant beta-glucosides are toxic because they inhibit trehalase, a key enzyme
      controlling glucose availability in insects.

PMID- 16458034
TI  - Lack of association between microsomal triglyceride transfer protein gene
      polymorphism and liver steatosis in HCV-infected patients.
AB  - OBJECTIVES: It has been shown that the HCV-core protein reduces the activity of
      microsomal triglyceride transfer protein (MTP) and could lead to steatosis in HCV
      infected patients. The aim of our study was to investigate the influence of a
      functional polymorphism in the promoter region of the MTP gene (493G/T) on the
      development of HCV-related steatosis. METHODS: Eighty-six chronic hepatitis C
      patients were studied to assess: the effects of body mass index, age, HCV
      genotype, and 493G/T MTP polymorphism on steatosis. RESULTS: Steatosis was
      observed in 39 patients (45.3%). The 493G/T MTP polymorphism were not related to
      the development of steatosis. CONCLUSION: The functional G/T MTP polymorphism do
      not seem to play any role in the development of steatosis in chronic hepatitis C.

PMID- 16458035
TI  - Suppression of pattern-recognition receptor TLR4 sensing does not alter lung
      responses to pneumovirus infection.
AB  - Toll-like receptors (TLR) are an important component in the innate immune
      response to a wide variety of pathogens. Recently, a series of studies has
      addressed the hypothesis that TLR4 also participates in the host innate response
      against respiratory syncytial virus (RSV), the leading cause of lower respiratory
      tract infections in infants and young children. In most of the studies available,
      RSV, which is not a natural pathogen of mice, has been systematically used in
      mouse models of human bronchiolitis, with conflicting results. Pneumonia virus of
      mice (PVM), a member of the pneumovirus genus, shares many similarities with RSV.
      The serological and structural relationships that exist between them suggest that
      the immune response to these viruses may be similar in their respective natural
      hosts. To determine the role of TLR4 in host defense against PVM, TLR4-competent
      and TLR4-deficient mice were intranasally infected with PVM. Variation of body
      weight, pulmonary function values, histopathology, and pulmonary viral loads were
      analyzed. None of the investigated clinical, functional, histological and
      virological parameters was different between strains, which demonstrates that the
      sensitivity of the mouse to its natural pneumovirus infection is independent of
      the presence or absence of TLR4 sensing.

PMID- 16458036
TI  - [Amniotic fluid embolism: two case reports].
AB  - We report two cases of amniotic fluid embolism, confirmed by histological
      examination. Both patients had an immediate post-partum haemorrhage that required
      an haemostatic hysterectomy. A typical symptomatology of amniotic fluid embolism
      revelated the first case. The patient survived without any sequelae. In the
      second case, amniotic fluid embolism occurred immediately after the delivery. The
      patient developed an acute respiratory distress with a shock syndrome. Despite
      haemostatic hysterectomy and resuscitative efforts, she died 6 days later.

PMID- 16458037
TI  - Basal ganglia activation in Parkinson's disease.
AB  - The objective of this study was to compare basal ganglia activation in patients
      with Parkinson's disease to that of healthy controls, using functional MRI
      (fMRI). Six mildly-affected patients, off antiparkinsonian medications for at
      least 12h, and seven age-matched controls performed a unilateral motor switching
      task during fMRI data acquisition. Clear differences in basal ganglia activation
      were seen, with control subjects showing greater activation during both the left
      and right movement sessions. We observed activation of right sided basal ganglia
      structures in both groups, particularly with right sided movements, with caudate
      activation noted most frequently. This observation is consistent with right
      caudate involvement in the learning of new tasks and in association with
      externally paced movements.

PMID- 16458038
TI  - Good tumor control and survivals of squamous cell carcinoma of buccal mucosa
      treated with radical surgery with or without neck dissection in Taiwan.
AB  - The aim was to analyze the survival and prognostic factors in 232 patients with
      squamous cell carcinoma of the buccal mucosa (BSCC) treated with radical surgery
      with or without neck dissection (ND). The 5-year survivals for local,
      locoregional control, overall, disease-free, and disease-specific were
      demonstrated. Pathologic nodal status was the independent risk factor for local
      and locoregional control. Both pathologic nodal status and cell differentiation
      were the significant prognostic factors of disease-free survival. For cT1N0,
      11.1% had neck metastases. All were tumor depth of > or =6 mm. Our result showed
      a relatively better tumor control and survivals in BSCC with radical surgery with
      or without ND. The possible reason may be due to the benefit from widely surgical
      resection with ND and post-operative radiotherapy or concurrent chemoradiotherapy
      in those with risk factors. In treating early cT1N0, we suggest that elective ND
      is indicated only when tumor depth > or =6 mm.

PMID- 16458039
TI  - HRPT2 gene alterations in ossifying fibroma of the jaws.
AB  - Ossifying fibroma (OF) is a benign neoplasm related to bone characterized by a
      progressive enlargement of the affected jaw. Recently, the candidate tumor
      suppressor gene HRPT2 was identified and alterations in this gene were related
      with the Hyperparathyroidism-jaw tumor syndrome that is characterized by
      parathyroid adenoma or carcinoma, fibro-osseous lesions (mainly OF) of the jaws,
      and renal lesions. The purpose of the present study was to evaluate the HRPT2
      gene in OF. Tumour and blood samples were obtained from 3 patients with OF and
      one with juvenile ossifying fibroma (JOF). The results demonstrated three novel
      mutations in two out of three genotyped OF's. Interestingly, one of these
      patients showed a germ-line mutation after blood analysis. RT-PCR amplification
      was performed to analyze HRPT2 mRNA expression and only wild-type HRPT2
      transcript was found in all tumours. Investigation of the parafibromin protein by
      immunohistochemistry showed a similar pattern of immunolocalization with strong
      nuclear and cytoplasmic staining in all cases. In conclusion, the present study
      shows for the first time mutations of HRPT2 gene in OF and suggests that OF may
      arise due to haploinsufficiency of the HRPT2 gene.

PMID- 16458040
TI  - Annotating the genome of Medicago truncatula.
AB  - Medicago truncatula will be among the first plant species to benefit from the
      completion of a whole-genome sequencing project. For each of these species,
      Arabidopsis, rice and now poplar and Medicago, annotation, the process of
      identifying gene structures and defining their functions, is essential for the
      research community to benefit from the sequence data generated. Annotation of the
      Arabidopsis genome involved gene-by-gene curation of the entire genome, but the
      larger genomes of rice, Medicago and other species necessitate the automation of
      the annotation process. Profiting from the experience gained from previous whole
      genome efforts, a uniform set of Medicago gene annotations has been generated by
      coordinated international effort and, along with other views of the genome data,
      has been provided to the research community at several websites.

PMID- 16458041
TI  - Paleopolyploidy and gene duplication in soybean and other legumes.
AB  - Two of the most important observations from whole-genome sequences have been the
      high rate of gene birth and death and the prevalence of large-scale duplication
      events, including polyploidy. There is also a growing appreciation that
      polyploidy is more than the sum of the gene duplications it creates, in part
      because polyploidy duplicates the members of entire regulatory networks. Thus, it
      may be important to distinguish paralogs that are produced by individual gene
      duplications from the homoeologous sequences produced by (allo)polyploidy. This
      is not a simple task, for several reasons, including the chromosomally cryptic
      nature of many duplications and the variable rates of gene evolution. Recent
      progress has been made in understanding patterns of gene and genome duplication
      in the legume family, specifically in soybean.

PMID- 16458042
TI  - Regulation of terpenoid and benzenoid production in flowers.
AB  - The production and emission of fragrant molecules by flowers are strictly
      regulated during the floral lifespan and often peak when pollinators are active.
      The best-studied classes of floral volatiles are benzenoids and terpenoids. The
      production of these molecules appears to be primarily regulated at the level of
      precursor biosynthesis. The genes from the petunia floral shikimate pathway,
      which provides the precursors for the formation of benzenoids, have recently been
      shown to be regulated by a MYB transcription factor. The floral terpenoids of
      snapdragon appear to be derived exclusively from the methyl-erythritol-phosphate
      pathway in plastids. This pathway controls precursor levels for geranyl
      diphosphate synthase, which in turn is transcriptionally regulated.

PMID- 16458043
TI  - Unraveling abiotic stress tolerance mechanisms--getting genomics going.
AB  - Homeostasis, a set-value for metabolism under optimal conditions, is rarely
      achieved by plants because of the cost exerted by external stress factors:
      climatic, biotic, and nutrient imbalances. Among these, stresses caused by
      abiotic conditions, such as temperature extremes (freezing, cold and heat), water
      availability (drought and ion excess) and ion toxicity (salinity and heavy
      metals), have been difficult to dissect because defense responses to abiotic
      factors require regulatory changes to the activation of multiple genes and
      pathways. Genomics technologies that have emerged during the past decade have
      been useful in addressing, in an integrated fashion, the multigenicity of the
      plant abiotic stress response through genome sequences; cell-, organ-, tissue-
      and stress-specific transcript collections; transcript, protein and metabolite
      profiles and their dynamic changes; protein interactions; and mutant screens.

PMID- 16458044
TI  - Regulatory links between carbon and nitrogen metabolism.
AB  - The metabolism of carbon- and nitrogen-containing compounds is fundamental to all
      forms of life. To cope with changing environmental conditions, bacteria have to
      sense the nutrient supply and adapt their metabolism accordingly. In addition to
      nutrient- and pathway-specific responses, they integrate information from the
      different branches of metabolism to coordinate the control of the expression of
      many metabolic genes. Two major players interconnecting carbon and nitrogen
      regulation are the PII proteins and the phosphotransferase system. Moreover,
      several DNA-binding transcription regulators sense signals are derived from both
      carbon and nitrogen metabolism. The regulatory networks enable the bacteria to
      make the appropriate metabolic responses to changing nutrient availabilities in
      the environment.

PMID- 16458045
TI  - Genotoxicity and carcinogenicity studies of antihypertensive agents.
AB  - This survey is a compendium of genotoxicity and carcinogenicity information of
      antihypertensive drugs. Data from 164 marketed drugs were collected. Of the 164
      drugs, 65 (39.6%) had no retrievable genotoxicity or carcinogenicity data; this
      group was comprised largely of drugs marketed in a limited number of countries.
      The remaining 99 (60.4%) had at least one genotoxicity or carcinogenicity test
      result. Of these 99, 48 (48.5%) had at least one positive finding: 32 tested
      positive in at least one genotoxicity assay, 26 in at least one carcinogenicity
      assay, and 10 gave a positive result in both at least one genotoxicity assay and
      at least one carcinogenicity assay. In terms of correlation between results of
      the various genotoxicity assays and absence of carcinogenic activity in both mice
      and rats 2 of 44 non-carcinogenic drugs tested positive in the in vitro bacterial
      mutagenesis assay, 2 of 9 tested positive in the mouse lymphoma assay, none of 14
      tested positive for gene mutation at the hprt locus, 5 of 25 tested positive in
      in vitro cytogenetic assays, none of 31 in in vivo cytogenetic assays, and none
      of 14 in inducing DNA damage and/or repair in in vitro and/or in vivo assays.
      Concerning the predictivity of genetic toxicology findings for long-term
      carcinogenesis assays, 75 drugs had both genotoxicity and carcinogenicity data;
      of these 37 (49.3%) were neither genotoxic nor carcinogenic, 14 (18.7%) were non
      carcinogens which tested positive in at least one genotoxicity assay, 14 (18.7%)
      were carcinogenic in at least one sex of mice or rats but tested negative in
      genotoxicity assays, and 10 (13.3%) were both genotoxic and carcinogenic. Only 42
      of the 164 marketed antihypertensives (25.6%) had all data required by the
      guidelines for testing of pharmaceuticals.

PMID- 16458046
TI  - Photo-oxidation of diglycine in confined media Relaxation of longitudinal
      magnetization in spin correlated radical pairs.
AB  - Time-resolved electron paramagnetic resonance spectra (X-band) of correlated
      radical pairs created in AOT reverse micelles are presented and simulated using
      the microreactor model. They are discussed in terms of the two-site model with a
      particular emphasis on longitudinal relaxation mechanisms. The geminate radical
      pair is created by photo-oxidation of dyglicine by the excited triplet states of
      an anthraquinone salt. The strong chemically induced electron spin polarization
      observed is due to three mechanisms: TM, RPM, and SCRPM. Relative contributions
      from these mechanisms depend on the water pool volume and the time of
      observation. There are three types of longitudinal relaxation in radical pairs.
      The first is relaxation of the RPM induced longitudinal magnetization in spin
      correlated radical pairs. The second is the longitudinal relaxation in radical
      pairs which are not correlated (with a zero value of the double quantum
      coherence). In such pairs, the generation of longitudinal magnetization due to
      RPM is impossible, and the spin-selective recombination of the pairs is
      ineffective. Under all experimental conditions, the first type of relaxation is
      slower than the second type. For both, the physical mechanism leading to
      relaxation is modulation of the Heisenberg electron spin exchange interaction.
      This is an internal relaxation process. The third relaxation type occurs in
      radical pairs due to ordinary longitudinal relaxation in non-interacting
      radicals. Normally, relaxation of the third type is the slowest of the three.
      This explains time and micelle size dependence of the relative contribution of
      RPM into TREPR spectra. It seems reasonable to suggest that the creation of the
      initial spin state populations is partially adiabatic.

PMID- 16458048
TI  - The effects of thermal quenching on the excited-state intramolecular proton
      transfer reaction in 3-hydroxyflavones.
AB  - The 3-hydroxyflavone (3HF) and its derivatives are the classical objects in the
      studies of the mechanisms of excited-state intramolecular proton transfer (ESIPT)
      reaction due to very frequent observation of two separate bands in fluorescence
      emission belonging to reactant and reaction product. Those of them possessing
      electron-donor groups in 4' position find many applications as fluorescence
      sensors and probes because of their much higher sensitivity of their two-band
      ratiometric response to interactions with the environment. We report on the
      strong differences between 3HF and such derivatives in the behavior of their
      fluorescence spectra as a function of temperature. The thermal quenching changes
      the intensity ratio of two bands strongly for 3HF but does not change it for its
      studied derivatives. These results are interpreted in terms of different kinetic
      mechanisms of ESIPT reaction. In 3HF the equilibrium between the two excited
      state species is not established prior to emission, so that the ESIPT reaction is
      under kinetic control, but in these derivatives the equilibrium is established
      faster than the emission and the reaction is under thermodynamic control. We
      suggest that the thermal perturbation of fluorescence spectra can be an extremely
      simple and convenient alternative to time-resolved spectroscopy for determining
      if slow irreversible or fast reversible ESIPT reaction gives rise to two bands of
      fluorescence spectra of similar magnitude. This is essential for the development
      of new wavelength-ratiometric fluorescence sensors and probes.

PMID- 16458049
TI  - Raman spectroscopic studies on tropolone complexes with La, Nd, Sm, Yb.
AB  - The complexes of tropolone (HL) with different lanthanide metals of lanthanum
      (La), neodymium (Nd), samarium (Sm), ytterbium (Yb) have been prepared
      respectively in the non-aqueous solution by the direct electrochemical oxidation
      of sacrificial metal anodes, and characterized by normal Raman spectroscopy. By
      comparing the spectra of the ligands and their complexes, the stretching
      vibrational band of OH disappeared in complexes, and the frequencies shifts of
      some relevant bands were observed, particularly for the stretching vibration of
      CO. In the low frequency region, new metal ion sensitive bands at 400-700 cm(-1)
      were observed, which could be assigned to the stretching vibrational mode of the
      bonding of lanthanide with oxygen. The stretching vibration of lanthanide-oxygen
      of tropolonate complexes showed a metal ion sensitivity. All the obvious change
      in spectral feature of Raman spectra revealed that CO and OH were coordinated
      with the center metal ions through oxygen atoms. Based on Raman results, the
      structures of the above complexes were proposed.

PMID- 16458050
TI  - Vibrational spectroscopic studies and ab initio calculations of sulfanilamide.
AB  - FT-Raman and FT-IR spectra of sulfanilamide were recorded and analyzed. The
      vibrational frequencies of the compound have been computed using the Hartree
      Fock/6-21G(*) basis and compared with the experimental values. The assignments of
      the observed bands were made on the basis of available literature.

PMID- 16458051
TI  - Spectroscopic and thermal studies of chromium(III), molybdenum(VI) and
      ruthenium(0) complexes of maleic hydrazide.
AB  - Interaction of maleic hydrazide (LH(2)) with [Cr(CO)(6)] in air at atmospheric
      pressure resulted in the formation of the complex [(LH)Cr(mu-O)(2)Cr(LH)] (1).
      Reaction of LH(2) with [Mo(CO)(6)] in air also gave the complex [(LH(2))O(2)Mo(mu
      O)(2)MoO(2)(LH(2))] (2). Under the same conditions, the reaction of LH(2) with
      [Ru(3)(CO)(12)] resulted in the formation of the tricarbonyl complex
      [Ru(CO)(3)(LH(2))] (3). The complexes were characterized by elemental analysis,
      IR, and (1)H NMR spectroscopy. The thermal properties of the complexes were
      investigated by thermogravimetry technique.

PMID- 16458052
TI  - Study of upconversion fluorescence property of novel Er3+/Yb3+ co-doped tellurite
      glasses.
AB  - Er3+/Yb3+ co-doped TeO2-B2O3-Nb2O5-ZnO (TBN) glasses were prepared. The
      absorption spectra and upconversion luminescence spectra of TBN glasses were
      measured and analyzed. The upconversion emission bands centered at 530, 546 and
      658 nm were observed under the excitation at 975 nm, corresponding to the
      transitions of 2H11/2-->4I15/2, 4S3/2-->4I15/2 and 4F9/2-->4I15/2 respectively.
      The ratio of red emission to green emission increases with an increasing of Yb3+
      ions concentration. According to the quadratic dependence on excitation power,
      the possible upconversion mechanisms and processes were discussed.

PMID- 16458053
TI  - Spectroscopic characterization of zinc oxide nanorods synthesized by solid-state
      reaction.
AB  - Well-crystallized zinc oxide nanorods have been fabricated by single step solid
      state reaction using zinc acetate and sodium hydroxide, at room temperature. The
      sodium lauryl sulfate (SLS) stabilized zinc oxide nanorods were characterized by
      using X-ray diffraction, Fourier transform infrared spectroscopy, transmission
      electron microscopy and photoluminescence spectroscopy. The X-ray diffraction
      revealed the wurtzite structure of zinc oxide. The size estimation by XRD and TEM
      confirmed that the ZnO nanorods are made of single crystals. The growth of zinc
      oxide crystals into rod shape was found to be closely related to its hexagonal
      nature. The mass ratio of SLS:ZnO in the nanorods was found to be 1:10 based on
      the thermogravimetric analysis. Blue shift of photoluminescence emission was
      noticed in the ZnO nanorods when compared to that of ZnO bulk. FT-IR analysis
      confirmed the binding of SLS with ZnO nanorods. Apart from ease of preparation,
      this method has the advantage of eco-friendliness since the solvent and other
      harmful chemicals were eliminated in the synthesis protocol.

PMID- 16458054
TI  - Dielectric spectroscopy of some heteronuclear amino alcohol complexes.
AB  - The temperature dependent dielectric spectroscopic properties of two
      heteronuclear complexes of monoethanolamine (MEA) at a wide temperature range
      (303-413 K) were investigated by impedance spectroscopy, in the frequency range
      from 100 Hz to 100 kHz. The frequency dependence of the impedance spectra plotted
      in the complex plane shows semi-circles. The Cole-Cole diagrams have been used to
      determine the molecular relaxation time, tau. The temperature dependence of tau
      is expressed by thermally activated process. Relaxation frequencies corresponding
      to the rotation of the molecules about their long axes are expected to lie above
      10 MHz and exhibit Arrhenius behavior, where a single slope is observed with
      activation energy values equal to 0.67 and 0.78 eV. The ac conductivity sigma(ac)
      (omega) is found to vary as omega(s) with the index s<or=1, indicating a dominant
      hopping process at low temperatures. The dielectric permittivity dependence as a
      function of frequency and temperature have been determined and showed a strong
      dispersion at frequency lower than 10 kHz. Capacitance and losses, tandelta,
      decreased with increasing frequency and increased with increasing temperature.
      The analysis of the data reveals that such characteristics are in good agreement
      with semi-conducting features based mainly on the hopping mechanism.

PMID- 16458055
TI  - Solid state linear-dichroic infrared spectral and theoretical analysis of
      methionine-containing tripeptides.
AB  - Stereo structural characterization of methionine-containing tripeptides glycine
      glycine-methionine (Gly-Gly-Met) and methionine-glycine-glycine (Met-Gly-Gly) is
      carried out by means of linear-dichroic infrared spectral analysis of oriented as
      nematic liquid crystal suspension solid samples. Thus obtained data are compared
      with theoretical ones received by ab initio calculations (Hartree-Fock level of
      theory and 6-31G** basis set). An IR-spectral characterization of both
      tripeptides is included as well.

PMID- 16458056
TI  - Synthesis and spectroscopic characterization of nickel(II) complexes of 1
      benzotriazol-1-yl-[(p-X-phenyl)hydrazone]propan-2-one.
AB  - The reaction of NiCl(2).H(2)O with 1-benzotriazol-1-yl-[(p-X
      phenyl)hydrazone]propan-2-one, X=H (HL(1)), X=Cl (HL(2)), X=Br (HL(3)) and X=Me
      (HL(4)), gave the complexes [(HL)NiCl(2)] x nH(2)O and [LNi(OH)](2), where L is
      the monobasic anion of HL(2) or HL(3). The nature of the products is solvent and
      ligand dependent. The complexes are characterized by elemental analyses, molar
      conductivity, magnetic moments and spectroscopic (IR and UV/vis) measurements.
      The IR showed that the ligands act as neutral bidentate coordinated to the
      nickel(II) through the azomethine nitrogen and carbonyl oxygen atoms in case of
      [(HL)NiCl(2)] x nH(2)O. In case of [LNi(OH)](2), the ligands are monobasic
      bidentate bonded to the nickel(II) through the azomethine nitrogen and the
      enolato oxygen atoms. The room temperature magnetic moment values of 1.58-2.49
      B.M. for [(HL)NiCl(2)] x nH(2)O and [LNi(OH)](2) and their electronic spectral
      data indicate that these complexes have square planar-tetrahedral equilibrium.
      The values of 1.61 and 1.58 B.M. for the hydroxo-complexes support their dimeric
      nature. The electronic spectral of [(HL)NiCl(2)] x nH(2)O and [LNi(OH)](2) in
      pyridine or alpha-picoline indicated the formation of six-coordinate adducts. The
      hydroxo-complexes reacted with different Lewis bases to give the complexes
      [L(2)Ni(L(s))(2)], where L(s)=Py, 2-Pic, 3-Pic, 4-Pic or n-PrNH(2). The
      relationship between the pK(b) of the Lewis base and the upsilon(Ni-O) of the
      ligand and upsilon(Ni-N) of the Lewis base was studied. The different ligand
      field parameters are calculated for the parent ligands in solutions and the solid
      mixed ligand complexes. The data showed that both are associated with a distorted
      octahedral ligand field around the nickel(II) and the ligand fields in solution
      are different from that in solid. The extent of distortion for the parent
      complexes is more than that in the solid adducts. Furthermore, the data showed
      that the nickel-ligand bonding in [LNi(OH)](2) is more covalent than in
      [L(2)Ni(L(s))(2)].

PMID- 16458058
TI  - Fluorescence quenching method for the determination of sodium carboxymethyl
      cellulose with acridine yellow or acridine orange.
AB  - In near neutral to weak basic media, sodium carboxymethyl cellulose (NaCMC) will
      dissociate to become a macro polymeric anion, which can react with acridine
      yellow (AY) or acridine orange (AO) to form an ion-association complex resulting
      in fluorescence quenching of the acridine dyes. The maximum fluorescence
      quenching wavelength is 505 nm (lambda(ex)=440 nm) for AY system and 530 nm
      (lambda(ex)=493 nm) for AO system, respectively. The fluorescence quenching
      values (DeltaF) are directly proportional to the concentrations of NaCMC and the
      linear ranges are 20.0-4000 microg/L for AY system and 20.0-7000 microg/L for AO
      system, separately. This method has high sensitivity and the detection limits for
      NaCMC are 58.0 microg/L (AY system) and 157.2 microg/L (AO system). The effects
      of coexistent substance have been investigated, and the results show that this
      method has a relatively good selectivity. A fluorescence quenching method for the
      determination of NaCMC based on the ion-association reactions of CMC polymeric
      anion with a basic acridine dye was developed. The method is sensitive, simple
      and fast.

PMID- 16458057
TI  - Micro-structural study of the GeS2-In2S3-KCl glassy system by Raman scattering.
AB  - Room temperature Raman spectra of samples on three serials within the GeS(2)
      In(2)S(3)-KCl glassy system have been investigated systematically. According to
      XRD patterns and Raman spectra of several pseudo-binary systems, the Cl atoms,
      which was added into the GeS(2)-In(2)S(3) glasses through KCl, was considered to
      be leading to the breaking of In-In bonds among the S(3)In-InS(3) ethane-like
      units and the forming of InS(4-x)Cl(x), InS(6-x)Cl(x) mixed polyhedra.
      Considering the effect of K(+) ions upon mixed anion units (InS(4-x)Cl(x) and
      InS(6-x)Cl(x)) and the corresponding micro-structural model, the Raman spectral
      evolution of the GeS(2)-In(2)S(3)-KCl glasses can be elucidated successfully. The
      microstructure of the GeS(2)-In(2)S(3)-KCl glasses was considered to be that the
      potassium atoms, which exist in the form of chlorine atoms as its nearest
      neighbor, are homogeneously dispersed in the glassy net formed by the micro
      structural units such as InS(4), InS(6), InS(4-x)Cl(x), InS(6-x)Cl(x), GeS(4)
      polyhedra and S(3)In(Ge)-In(Ge)S(3) ethane-like units.

PMID- 16458059
TI  - Synthesis and spectroscopic studies of mixed-ligand and polymeric dinuclear
      transition metal complexes with bis-acylhydrazone tetradentate ligands and 1,10
      phenanthroline.
AB  - Two types of dinuclear copper(II) and nickel(II) complexes with two tetradentate
      N2O2 donor ligands 1,4-bis(1-anthranoylhydrazonoethyl)benzene (L1), 1,4-bis(1
      salicyloylhydrazonoethyl)benzene (L2) and N,N'-bidentate heterocyclic base [1,10
      phenonthroline (phen)] have been synthesized and characterized by elemental
      analysis, infrared spectra, UV-vis electronic absorption spectra and magnetic
      susceptibility measurements. The reaction of metal(II) acetates with the solution
      containing ligand and 1,10-phenonthroline in methanol gives mixed-ligand
      dinuclear metal(II) complexes with general formula [M2L(phen)2]Cl2 (L=L1 or L2),
      whereas, the ligands react with metal(II) acetates to form polymeric dinuclear
      complexes with general formula [(M2L2)n] (L=L1 or L2). In the complexes, the
      ligands act as dianionic tetradentate and coordination takes place in the enol
      tautomeric form with the enolic oxygen and azomethine nitrogen atoms while the
      phenolic hydroxyl and amino groups of aroylhydrazone moiety do not participate in
      coordination. The effect of varying pH and solvent on the absorption behavior of
      both ligands and complexes has been investigated.

PMID- 16458060
TI  - Surface-enhanced Raman scattering and the adsorption behavior of (RS)
      phenylsuccinic acid.
AB  - The surface geometry of (RS)-phenylsuccinic acid molecule was studied by analysis
      of the SERS spectra of aromatic dicarboxylic acid adsorbed on silver colloid
      surfaces. For a reliable analysis of the SERS spectrum, we also performed density
      functional theoretical calculations. The SERS spectral features indicated that
      the RSPSA molecules should bound to the silver as dicarboxylate, with a strongly
      tilted orientation with respect to the normal to the surface. Such a tilted
      orientation was presumed to occur by the simultaneous sigma and pi-type
      coordination of carboxylate groups to silver surface caused by the steric
      hindrance and electrostatic repulsion between the two carboxylate groups, and
      thereby RSPSA on silver was easily displaced with aromatic carboxylic acids. A
      sigma-type coordination therefore seemed to be more important than a pi-type
      coordination for aromatic carboxylic acid derivatives to assemble on a silver
      surface. The large enhancement of in-plane bending, out of plane bending and ring
      breathing modes in the surface-enhanced Raman scattering spectrum indicates that
      the molecule is adsorbed on the silver surface in a 'at least vertical'
      configuration, with the ring perpendicular to the silver surface.

PMID- 16458061
TI  - 1H-15N NMR studies of the complex bis(S-allyl-L-cysteinate)palladium(II).
AB  - 1H-15N 2D NMR data for S-allyl-L-cysteine (deoxyalliin) and for bis(S-allyl-L
      cysteinate)palladium(II) complex are presented in this manuscript. Large upfield
      15N NMR shift of the amine nitrogen in the spectrum of the complex when compared
      to the spectrum of the ligand shows clearly coordination of S-allyl-L-cysteine,
      in the anion form, to palladium(II) through the NH2 group.

PMID- 16458062
TI  - Spectral and thermal study on the adduct formation between square planar
      nickel(II) chelates and some bidentate ligands.
AB  - Adducts of Ni(II)-square planar complexes [Ni(beta-dik)(Me(4)en)](+), with a
      series of bidentate ligands (L), where beta-dik=acetylacetonate (acac) and
      benzoylacetonate (bzac), Me(4)en=N,N,N',N'-tetramethylethylenediamine and
      L=Me(4)en, 2,2'-bipyridine (bipy), ethylenediamine (en) and oxalate (C(2)O(4)(2
      )) have been synthesized and characterized by spectral, thermal and magnetic
      measurements. Formation constants of the adducts formed from a series of ternary
      mixed Ni(II) complexes with the general formula [Ni(beta-dik)(diam)](+) with 1,10
      phenanthroline (phen), 2,2'-bipyridine (bipy) and pyridine were
      spectrophotometrically determined. Thermodynamic parameters of the adduct
      formation between nickel(II) square-planar chelates and pyridine (py), 2,2'
      bipyridine (bipy) and acetylacetone (acac) were also spectrophotometrically
      determined in 1,2-dichloroethane. The thermal stability of the isolated adducts
      was studied using thermogravimetry and the decomposition schemes of the adducts
      were given.

PMID- 16458063
TI  - Infrared spectra and molar absorption coefficients of the 20 alpha amino acids in
      aqueous solutions in the spectral range from 1800 to 500 cm(-1).
AB  - In this work, we present the absorption spectra and molar coefficients of all 20
      amino acids in aqueous solutions down to 500 cm(-1). The spectral region between
      1200 and 500 cm(-1) was yet disregarded for protein infrared spectroscopy, mainly
      due to the strong H(2)O absorption. Absorption spectra were obtained mainly for
      physiological relevant pH region. Intense bands for aromatic amino acids,
      histidine and such with OH group could clearly be identified throughout the given
      spectral region. For sulfur-containing amino acids cysteine and methionine some
      strong bands besides the weak carbon-sulfur stretching vibration was shown.
      Effects of aqueous solution environment, pH, protonation states were discussed,
      together with previously reported data from theoretical approaches. With this
      complete set of spectral information application to proteins in the whole mid
      infrared region could be described precise and the potential of the lower
      spectral region to study typical cofactor ligands like histidine, shown.

PMID- 16458064
TI  - Density functional calculations on the structure, vibrational frequencies and
      normal modes of 7-Azaindole.
AB  - The structure, harmonic frequencies and vibrational mode assignments for 7
      Azaindole monomer and its isotopic analogous are calculated using BP86 method
      employing the 6-31G(*) basis set. The results of the optimized molecular
      structure obtained on the basis of these calculations are presented and
      critically compared with the experimental IR data recorded in gas phase. The
      Raman and IR spectral data of 7-Azaindole obtained in solid phase have also been
      included. The normal mode analysis has been carried out for all the modes. The
      analysis of vibrational data for 7-Azaindole has been qualitative both in terms
      of assignments as well as the description of the normal modes. Potential energy
      distribution has been calculated for the perfect assignment of the vibrational
      modes.

PMID- 16458065
TI  - Aggregation of two carboxylic derivatives of porphyrin and their affinity to
      bovine serum albumin.
AB  - Aggregation of two porphyrin derivatives with carboxylic groups, 4-oxo-4-((4
      (10,15,20-triphenyl-21H,23H-porphin-5-yl)phenyl)amino)butanoic acid (MAC) and
      4,4',4'',4'''-[21H,23H-porphine-5,10,15,20-tetrayltetrakis(4,1
      phenyleneimino)]tetrakis(4-oxo-butanoic acid) (TA4C), and their affinity to
      bovine serum albumin were investigated via absorption spectrometry, (1)H NMR and
      fluorescence spectrometry. MAC and its complexes with beta-cyclodextrin could
      form aggregates in an aqueous solution while TA4C was self-associated loosely.
      From the absorbance profiles of MAC in the titration of bovine serum albumin,
      hypochromicity was observed without any shift of the maximum absorbance
      wavelength. In both absorption spectra of TA4C in aqueous solutions and in solid
      state, three Q bands appeared in the visible region. In the measurements of
      absorption and fluorescence spectra upon titration of BSA, some spectral changes
      of TA4C were observed. The whole procedure of titration could be divided into
      three successive stages. The three-banded profiles of TA4C might be explained
      according to a loose dimer model.

PMID- 16458066
TI  - The life and death of URLs in five biomedical informatics journals.
AB  - OBJECTIVE: To determine the decay rate of Uniform Record Locators (URLs) in the
      reference section of biomedical informatics journals. METHODS: URL references
      were collected from printed journal articles of the first and middle issues of
      1999-2004 and electronically available in-press articles in January 2005. We
      limited this set to five biomedical informatics journals: Artificial Intelligence
      in Medicine, International Journal of Medical Informatics, Journal of the
      American Medical Informatics Association: JAMIA, Methods of Information in
      Medicine, and Journal of Biomedical Informatics. During a 1-month period, URL
      access attempts were performed eight times a day at regular intervals. RESULTS:
      Of the 19,108 references extracted from 606 printed and 86 in-press articles,
      1112 (5.8%) references contained a URL. Of the 1049 unique URLs, 726 (69.2%) were
      alive, 230 (21.9%) were dead, and 93 (8.9%) were comatose. URLs from in-press
      articles included 212 URLs, of which 169 (79.7%) were alive, 21 (9.9%) were dead,
      and 22 (10.4%) were comatose. The average annual decay, or link rot, rate was
      5.4%. CONCLUSION: The URL decay rate in biomedical informatics journals is high.
      A commonly accepted strategy for the permanent archival of digital information
      referenced in scholarly publications is urgently needed.

PMID- 16458067
TI  - Low frequency electrical stimulation through subdural electrodes in a case of
      refractory status epilepticus.
AB  - OBJECTIVE: We delivered low frequency stimulation through subdural electrodes to
      suppress seizures in a case of refractory status epilepticus (RSE). METHODS: A 26
      year-old female developed RSE after several days of febrile illness. Seizure
      control required continuous infusion of two anesthetics plus high doses of 2-4
      enteral antiepileptic drugs. After 3 months of RSE, subdural strips were placed
      to determine surgical candidacy. Five independent ictal onset zones were
      identified. Because she was a poor candidate for epilepsy surgery and had a poor
      prognosis, the implanted subdural electrodes were used to administer 0.5 Hz
      stimulations to the ictal onset zones in 30 min trains daily for 7 consecutive
      days in an attempt to suppress seizures. RESULTS: After 1 day of stimulation, one
      anesthetic agent was successfully discontinued. Seizures only returned by the 4th
      day when the second anesthetic had been reduced by 60%. Upon returning, seizures
      arose from only one of the 5 original ictal onset zones. Unfortunately, RSE
      persisted, and she eventually died. CONCLUSIONS: In this case of RSE, low
      frequency stimulation through subdural electrodes transiently suppressed seizures
      from all but one ictal onset zone and allowed significant reduction in seizure
      medication. SIGNIFICANCE: Low frequency cortical stimulation may be useful in
      suppressing seizures.

PMID- 16458068
TI  - The effect of CNS activation versus EEG arousal during sleep on heart rate
      response and daytime tests.
AB  - OBJECTIVE: To induce a heart rate change in normal subjects using auditory
      stimulation without inducing EEG arousals and to assess the effects on daytime
      functioning and compare results to auditory stimulation leading to short EEG
      arousals. METHODS: Six normal young men initially randomized into two groups (A
      and B) underwent 4 nights of nocturnal polysomnography (normal sleep on night 1,
      auditory stimulation without EEG arousal or normal sleep on nights 2 and 3 using
      Latin square design, and auditory stimulation with EEG arousal on night 4). MSLT
      and PVT were performed during days following nights 2-4. RESULTS: MSLT and PVT
      results showed significant differences after EEG arousal compared to stimulation
      without EEG arousal and to normal sleep; there were no significant differences
      after normal sleep compared to stimulation without EEG arousal. RR interval
      showed significant differences during undisturbed sleep compared to stimulation
      without EEG arousal and to stimulation with EEG arousal; RR interval without EEG
      arousal also differed significantly from RR interval with EEG arousal.
      CONCLUSION: Activation of the brain-stem can lead to autonomic nervous system
      (ANS) response without objective consequences the next day. SIGNIFICANCE: ANS
      responses induced by auditory stimulation during sleep without EEG arousal do not
      have the same effects on daytime sleepiness and performance as sleep
      fragmentation associated with EEG arousals.

PMID- 16458069
TI  - P300-based brain computer interface: reliability and performance in healthy and
      paralysed participants.
AB  - OBJECTIVE: This study aimed to describe the use of the P300 event-related
      potential as a control signal in a brain computer interface (BCI) for healthy and
      paralysed participants. METHODS: The experimental device used the P300 wave to
      control the movement of an object on a graphical interface. Visual stimuli,
      consisting of four arrows (up, right, down, left) were randomly presented in
      peripheral positions on the screen. Participants were instructed to recognize
      only the arrow indicating a specific direction for an object to move. P300
      epochs, synchronized with the stimulus, were analyzed on-line via Independent
      Component Analysis (ICA) with subsequent feature extraction and classification by
      using a neural network. RESULTS: We tested the reliability and the performance of
      the system in real-time. The system needed a short training period to allow task
      completion and reached good performance. Nonetheless, severely impaired patients
      had lower performance than healthy participants. CONCLUSIONS: The proposed system
      is effective for use with healthy participants, whereas further research is
      needed before it can be used with locked-in syndrome patients. SIGNIFICANCE: The
      P300-based BCI described can reliably control, in 'real time', the motion of a
      cursor on a graphical interface, and no time-consuming training is needed in
      order to test possible applications for motor-impaired patients.

PMID- 16458070
TI  - Dissociation between pain and the nociceptive blink reflex during psychological
      arousal.
AB  - OBJECTIVE: To investigate the effect of psychological arousal on pain ratings and
      the R2 component of the electrically evoked blink reflex to a 'pure' noiciceptive
      stimulus. METHODS: Pain ratings and R2 to a noiciceptive stimulus (pulse width
      0.3ms, 2mA, delivered from a concentric electrode attached to the supraorbital
      region of the forehead) were investigated in 16 healthy participants before and
      during a serial subtraction task, and in 16 control participants who sat quietly
      during nociceptive stimulation. RESULTS: Pain ratings decreased whereas R2
      amplitude increased during the serial subtraction task. CONCLUSIONS: Supra-spinal
      rather than spinal mechanisms inhibited pain perception during psychological
      arousal. Moreover, psychological arousal facilitated the R2 component of the
      blink reflex to a nociception-specific stimulus. SIGNIFICANCE: Supra-spinal
      influences need to be considered during clinical evaluation of the trigeminal
      nociceptive blink reflex.

PMID- 16458071
TI  - Crisis, what crisis? Control of Rhodesian sleeping sickness.
AB  - There is an urgent need for cost-effective strategies for the sustainable control
      of Trypanosoma brucei rhodesiense (Rhodesian) sleeping sickness, which is a fatal
      zoonotic disease that has caused devastating epidemics during the past century.
      Sleeping sickness continues to be controlled by crisis management, using active
      case detection, treatment and vector control - activities that occur only during
      major epidemics; during the intervening periods, farmers and communities must
      fend for themselves. There are several methods for assessing the burden of this
      disease and there is a series of farmer-led methodologies that can be applied to
      reduce the burden of human and animal trypanosomiases.

PMID- 16458072
TI  - Codon modification of T cell receptors allows enhanced functional expression in
      transgenic human T cells.
AB  - Expression of native transgenic T cell receptors in recipient human T cells is
      often insufficient to achieve highly reactive T cell bulks. Here we show that
      codon modification of an HPV16E7-specific T cell receptor (TCR), together with
      omission of mRNA instability motifs and (cryptic) splice sites, leads to a
      dramatic increase in the expression levels of the transgenic TCRs in human CD8+ T
      cells. The codon-modified TCRs have been tested in three different configurations
      in the retroviral vector LZRS: (1) TCRalpha-IRES-GFP in combination with TCRbeta
      IRES-NGFR, (2) TCRalpha-IRES-TCRbeta, and (3) TCRalpha-2A-TCRbeta. T cells
      carrying the codon-modified TCRs are functionally active against target cells
      loaded with relevant peptide, model tumor cells expressing the specific epitope
      as well as cervical carcinoma cells. The significant improvements we report here
      in the functional expression of specific human TCRs will hopefully expedite
      clinical application of TCR transfer-based immunotherapy.

PMID- 16458073
TI  - The immunosuppressive effects of ciprofloxacin during human mixed lymphocyte
      reaction.
AB  - Interleukin (IL)-18, which is elevated in the plasma during acute rejection after
      organ transplantation, is known to induce the expression of intercellular
      adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on
      monocytes, the production of interferon (IFN)-gamma and IL-12 and the
      proliferation of lymphocytes during the human mixed lymphocyte reaction (MLR).
      Ciprofloxacin (CIP), which is useful for the clinical treatment of infections due
      to its antibacterial properties after transplantation, was shown to suppress the
      IFN-gamma and IL-12 production, the lymphocyte proliferation and the ICAM-1,
      B7.1, B7.2 and CD40 expression on monocytes during MLR in the presence of IL-18.
      CIP also induced the production of prostaglandin (PG) E2. In order to determine
      whether the effects of CIP on the expression of the activation markers were due
      to CIP-dependent production of PGE2, we examined the effect of cyclooxygenase
      (COX)-2 and protein kinase A (PKA) inhibitors on the actions of CIP. Thereby, the
      inhibitors were found to abolish the actions of CIP. These results therefore
      suggest that CIP might exert its immune modulatory effects via the production of
      PGE2.

PMID- 16458074
TI  - Robust HIV-specific immune responses were induced by DNA vaccine prime followed
      by attenuated recombinant vaccinia virus (LC16m8 strain) boost.
AB  - Recombinant vaccinia virus-based vaccine combined with DNA vaccine has produced a
      protective immune response against HIV infection in non-human primates. In this
      study, we explored the immunogenicity of a recombinant vaccinia virus (LC16m8
      strain), which has been used in children without severe side effects. The
      vaccinia virus expressing an HIV(89.6)env gene (vLC-Env) alone or combined with a
      DNA vaccine expressing the HIV(89.6)env gene (pCAG-Env) was characterized in
      BALB/c mice. Vaccination of vLC-Env induced much higher HIV-specific humoral and
      cell-mediated immune responses than that of pCAG-Env. Priming with pCAG-Env
      further enhanced vLC-Env induced immune responses, especially cell-mediated
      immune response. Moreover, efficient expression of Env protein was achieved
      following infection of bone marrow dendritic cells by vLC-Env in vitro.
      Administration of vLC-Env-infected dendritic cells to mice generated a high cell
      mediated immune response. These results demonstrate that priming with pCAG-Env
      and boosting with vLC-Env represents a logical candidate for vaccination against
      HIV infection.

PMID- 16458075
TI  - The Reconditioning Exercise and Chronic Obstructive Pulmonary Disease Trial II
      (REACT II): rationale and study design for a clinical trial of physical activity
      among individuals with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of
      mortality in the United States. In addition, persons with COPD are at risk for
      lower levels of physical activity, leading to further morbidity and mortality.
      Several studies have demonstrated that long-term exercise therapy confers
      benefits upon physical functioning among patients with COPD, and some studies
      indicate that embedding cognitive-behavioral interventions into group-mediated
      exercise programs is useful in promoting compliance to activity recommendations.
      However, compliance to long-term activity is low among COPD patients, and the
      effectiveness of behavioral interventions to enhance long-term activity among
      these patients has not been extensively explored. Thus, the primary objective of
      the Reconditioning Exercise and COPD Trial II (REACT II) trial is to determine
      whether a group-mediated cognitive-behavioral intervention will result in
      increased physical activity after 12 months, compared to a standard exercise
      therapy experience among older adults with COPD. The cognitive-behavioral
      intervention is designed to promote independent physical activity by encouraging
      participants to self-regulate physical activity with minimal dependence upon
      staff. The primary study outcome is kcal expended per week in moderate physical
      activity, and the study is designed to provide 90% power to detect a 400
      kcal/week difference in moderate energy expenditure between the two intervention
      groups. Other outcomes to be compared between the two interventions include
      physical function, self-reported physical disability, health-related quality of
      life, exercise capacity, body composition and inflammatory mediators.

PMID- 16458076
TI  - Serotonergic and glutamatergic neurons at the ventral medullary surface of the
      human infant: Observations relevant to central chemosensitivity in early human
      life.
AB  - Central chemoreception is the mechanism by which the brain detects the level of
      carbon dioxide (CO(2)) in the arterial blood and alters breathing accordingly in
      order to maintain it within physiological levels. The ventral surface of the
      medulla oblongata (VMS) of animals has long been recognized as a site of
      chemosensitivity, culminating in the recent identification of chemosensitive
      serotonergic (5-HT) and glutamatergic (Glut) neurons in this region. In this
      study, we analyzed the distribution of 5-HT and Glut neurons and their receptors
      in the arcuate nucleus (Arc) at the VMS of the human infant, using single-and
      double-label immunohistochemistry with specific antibodies. We also examined the
      expression of astrocytes, as experimental evidence suggests that astrocytes
      mediate, at least in part, central chemosensitivity via 5-HT and/or Glut
      receptors. We identified a small number of 5-HT neurons (approximately 5% of Arc
      neurons), distributed over the entire extent of the VMS, a large number of Glut
      neurons (approximately 95% of Arc neurons) that localized almost exclusively to
      the medial Arc, and a large number of astrocytes distributed across the entire
      extent of the VMS. The Arc also contained 5-HT(1A), kainate (GluR5), and 5-HT(2A)
      receptors, which localized predominantly to 5-HT neurons, glutamate neurons and
      astrocytes, respectively. Astrocytes also expressed the vesicular glutamate
      transporter 2 and low levels of 5-HT(1A) and kainate (GluR5) receptors,
      indicating that astrocytes may store and release glutamate, possibly in response
      to stimulation by 5-HT and/or Glut. These observations suggest that important
      functional interactions exist between 5-HT, glutamate, and astrocytes in the Arc.
      They also support the idea that the Arc is homologous to chemosensitive zones at
      the VMS in experimental animals. These data are important towards delineating the
      role of the human Arc in modulation of homeostasis, and its dysfunction in
      brainstem-associated pathologies such as the sudden infant death syndrome.

PMID- 16458077
TI  - Non-NMDA glutamatergic receptors modulate acetylcholine release in the rat
      subfornical organ area.
AB  - The present study was designed to examine whether glutamatergic receptor
      mechanisms modulate the release of acetylcholine (ACh) in the region of the
      subfornical organ (SFO) using intracerebral microdialysis methods in freely
      moving rats. Perfusion of either non-N-methyl-d-aspartate (NMDA) agonist
      quisqualic acid (QA, 50 microM) or kainic acid (KA, 50 microM) through the
      microdialysis probe significantly enhanced the ACh release in the SFO area. Local
      perfusion of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX, 10 and 50 microM) did not change the basal release of ACh. CNQX (10
      microM) administered together with either QA (50 microM) or KA (50 microM) in the
      SFO area antagonized the stimulant effect of the agonists on the ACh release. In
      urethane-anesthetized rats, repetitive electrical stimulation (500 microA, 10 Hz)
      of the medial septum (MS) significantly increased dialysate ACh concentrations in
      the region of the SFO. The increase in the ACh release elicited by the MS
      stimulation was significantly potentiated by perfusion of QA (50 microM), and the
      QA-induced potentiation was prevented by CNQX (10 microM) treated together with
      QA. These results show that the glutamatergic synaptic inputs enhance the ACh
      release in the SFO area through non-NMDA receptors. The data further suggest that
      the septal cholinergic inputs to the SFO area are potentiated by non-NMDA
      receptor mechanisms.

PMID- 16458078
TI  - Temporal/spatial expression and efflux activity of ABC transporter, P
      glycoprotein/Abcb1 isoforms and Bcrp/Abcg2 during early murine development.
AB  - ABC transporters pump out from cells a large number of endo- and xenobiotics
      including signal molecules and toxins; they are molecular markers of
      stem/progenitor cells as well. Here, we present the study of temporal/spatial
      patterns of Abcb1 isoforms and Abcg2 transporter expression and efflux activity
      in pre- and early postimplantation murine embryos. We found in 2-cell embryos
      abcb1a, abcb1b and abcg2 mRNAs which were believed to be maternally inherited.
      The expression of abcb1b and abcg2 genes was found in blastocysts and in 7 days
      postcoitum (dpc) embryos, while in 9dpc embryos beside of abcb1b/abcg2, the
      abcb1a gene was expressed. The abcb2 mRNA was detectable neither in pre- nor in
      postimplantation embryos. Moreover, we analysed temporal/spatial patterns of
      rhodamine 123/Hoechst 33342 efflux, which mirrors the ABC transporter phenotype,
      from individual cells of pre- and postimplantation murine embryos. The
      blastomeres of 2-, 4- and 8-cell embryos had efflux-inactive phenotype. Single,
      efflux-active cells emerged first in the morulae and their number increased in
      blastocyst inner cell mass. In 6 and 7 dpc embryos, all embryonic cells hold the
      efflux-active phenotype. Proximal embryonic endoderm of 6-8 dpc embryos contained
      two sub-domains: one consisted of efflux-active cells and another one of efflux
      inactive cells reflecting polarity of an embryo. Between 7 and 8 dpc, at the
      onset of organogenesis, the vehement surge of efflux-inactive embryonic cells
      occurred, and their number increased in 9 dpc embryos, which consequently
      contained few efflux-active cells.

PMID- 16458079
TI  - Embryonic expression profile of phospholipid hydroperoxide glutathione
      peroxidase.
AB  - The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is
      indispensable for murine embryonic development; yet, the cellular mechanisms
      leading to embryonic death around gastrulation are still unclear. To investigate
      PHGPx expression patterns during embryogenesis, we performed a detailed analysis
      that revealed a complex expression profile. Up to embryonic day 9.5, PHGPx was
      ubiquitously expressed, which was, albeit to a lower extent, maintained
      throughout later stages of embryogenesis. Notably, strong expression was
      frequently observed in epithelial tissue. A transient increase in PHGPx
      expression was detected in developing tissues, suggesting a crucial role for
      PHGPx in proliferation and differentiation. By semi-quantitative RT-PCR analysis
      we observed that the cytosolic form of PHGPx was present in embryonic and somatic
      tissues whereas the mitochondrial and nuclear forms were detectable only in
      testicular tissue. This strongly suggests that it is the cytosolic form of PHGPx
      that is indispensable for embryonic development.

PMID- 16458080
TI  - Identification of candidate genes at the corticoseptal boundary during
      development.
AB  - Cortical midline glia are critical to the formation of the corpus callosum during
      development. The glial wedge is a population of midline glia that is located at
      the corticoseptal boundary and expresses repulsive/growth-inhibitory molecules
      that guide callosal axons as they cross the midline. The glial wedge are the
      first cells within the cortex to express GFAP and thus may express molecules
      specific for glial maturation. The corticoseptal boundary is a genetically
      defined boundary between the cingulate cortex (dorsal telencephalon) and the
      septum (ventral telencephalon). The correct dorso-ventral position of this
      boundary is vital to the formation of both the glial wedge and the corpus
      callosum. Our aim was to identify genes expressed specifically within the glial
      wedge that might be involved in either glial differentiation, formation of the
      corticoseptal boundary or development of the corpus callosum. To identify such
      genes we have performed a differential display PCR screen comparing RNA isolated
      from the glial wedge with RNA isolated from control tissues such as the neocortex
      and septum, of embryonic day 17 mouse brains. Using 200 different combinations of
      primers, we identified and cloned 67 distinct gene fragments. In situ
      hybridization analysis confirmed the differential expression of many of the
      genes, and showed that clones G24F3, G39F8 and transcription factor LZIP have
      specific expression patterns in the telencephalon of embryonic and postnatal
      brains. An RNase Protection Assay (RPA) revealed that the expression of G39F8,
      G24F3 and LZIP increase markedly in the telencephalon at E16 and continue to be
      expressed until at least P0, during the period when the corpus callosum is
      forming.

PMID- 16458081
TI  - Claudin profiling in the mouse during postnatal intestinal development and along
      the gastrointestinal tract reveals complex expression patterns.
AB  - Members of the claudin protein family are key regulators of tight junction
      selectivity and are implicated in influencing development and cellular
      differentiation in the intestine and other tissues. The goal of the present study
      was to profile claudin gene expression and protein location during postnatal
      development of the mouse jejunum and in the adult mouse gut from duodenum to
      distal colon as a first step in understanding both normal claudin function and
      the pathologic implications of altered expression patterns. The relative
      expression of claudins 1-19 and other tight and adherens junction genes was
      determined by quantitative RT-PCR from six regions of normal mouse intestine and
      colon. Immunofluorescent localization was performed for claudins 1-5, 7, 8, 10,
      12, 15, and 18. Transcripts for claudins 1-5, 7-13, 17, and 18 were all detected
      in adult intestine, although their relative abundance differed up to 1000-fold
      within individual segments. In contrast to the unchanging expression and
      localization of ZO-1, occludin, and JAM, most claudins were expressed in
      decreasing or increasing gradients or in more complex patterns along the
      longitudinal axis of the intestine and the crypt to villus/surface
      differentiation axis. During neonatal development at days 1, 14, 28, and 90
      several claudins showed striking increases or decreases in transcript expression
      as well as changes in tissue localization along the crypt-villus axis. Claudin-19
      was only detected at days 1 and 14. This database provides a resource for
      investigating regional and developmental differences in permselectivity, crypt to
      villus/surface differentiation and neoplastic changes along the gut and during
      postnatal development.

PMID- 16458082
TI  - Osteocalcin and matrix Gla protein in zebrafish (Danio rerio) and Senegal sole
      (Solea senegalensis): comparative gene and protein expression during larval
      development through adulthood.
AB  - Bone Gla protein (Bgp or osteocalcin) and matrix Gla protein (Mgp) are important
      in calcium metabolism and skeletal development, but their precise roles at the
      molecular level remain poorly understood. Here, we compare the tissue
      distribution and accumulation of Bgp and Mgp during larval development and in
      adult tissues of zebrafish (Danio rerio) and throughout metamorphosis in Senegal
      sole (Solea senegalensis), two fish species with contrasting environmental
      calcium levels and degrees of skeletal reorganization at metamorphosis. Mineral
      deposition was investigated in parallel using a modified Alizarin red/Alcian blue
      protocol allowing sensitive simultaneous detection of bone and cartilage. In
      zebrafish, bgp and mgp mRNAs were localized in all mineralized tissues during and
      after calcification including bone and calcified cartilage of branchial arches.
      Through immunohistochemistry we demonstrated that these proteins accumulate
      mainly in the matrix of skeletal structures already calcified or under
      calcification, confirming in situ hybridization results. Interestingly, some
      accumulation of Bgp was also observed in kidney, possibly due to the presence of
      a related protein, nephrocalcin. Chromosomal localization of bgp and mgp using a
      zebrafish radiation hybrid panel indicated that both genes are located on the
      same chromosome, in contrast to mammals where they map to different chromosomes,
      albeit in regions showing synteny with the zebrafish location. Results in Senegal
      sole further indicate that, during metamorphosis, there is an increase in
      expression of both bgp and mgp, paralleling calcification of axial skeleton
      structures. In contrast with results obtained for previously studied marine
      fishes, in zebrafish and Senegal sole Mgp accumulates in both calcified tissues
      and non-mieralized vessel walls of the vascular system. These results suggest
      different patterns of Mgp accumulation between fish and mammals.

PMID- 16458083
TI  - Characterization of the expression of the ALK receptor tyrosine kinase in mice.
AB  - Anaplastic Lymphoma Kinase (ALK), a receptor tyrosine kinase, was first described
      as the fusion product causing a subtype of non-Hodgkin's lymphoma. To date Alk
      has been reported to be mainly expressed in CNS and other parts of the brain.
      Here we describe an extensive characterization of the mRNA and protein expression
      of ALK during mouse development. We show that mRNA and ALK protein show
      overlapping expressing patterns in specific regions of the central and the
      peripheral nervous systems. Furthermore, ALK is also expressed in the eye, nasal
      epithelium, olfactory nerve, tongue, skin, tissue surrounding the esophagus,
      stomach and midgut but not the hindgut. Expression of ALK is also found in testis
      and ovary.

PMID- 16458084
TI  - Molecular cloning and expression of two small leucine-rich proteoglycan (SLRP)
      genes, dspg3l and optcl, in zebrafish.
AB  - Epiphycan (DSPG3) and opticin are two class III small leucine-rich proteoglycans
      (SLRP). We isolated two zebrafish cDNAs, dspg3l and optcl, that encode proteins
      homologous to epiphycan and opticin in other vertebrates. Like epiphycans in
      other species, dspg3l is exclusively expressed in the developing notochord and
      cartilage. optcl is expressed transiently in the developing nervous system, eyes
      and somites much like opticin. The zebrafish dspg3l and optcl genes are located
      in linkage group 4 and 11, respectively. The genomic locations for both genes in
      zebrafish are syntenic with the genomic locations of dspg3 and opticin (optc) in
      human and mouse. Synteny and the expression patterns of these genes suggest that
      the dspg3l and optcl are the orthologs to the mammalian dspg3 and optc genes,
      respectively.

PMID- 16458085
TI  - Thermodynamic characterization of interactions between p27(Kip1) and activated
      and non-activated Cdk2: intrinsically unstructured proteins as thermodynamic
      tethers.
AB  - The cyclin-dependent kinase inhibitor (CKI) p27Kip1 plays a critical role in cell
      cycle regulation by binding and inhibiting (or activating) various cyclin
      dependent kinase (Cdk)/cyclin complexes. Thermal denaturation monitored by
      circular dichroism (CD) and isothermal titration calorimetry (ITC) were used to
      determine the relative stabilities and affinities of p27-KID (p27 kinase
      inhibitory domain) complexes with activated Cdk2 (phosphorylated at Thr160; P
      Cdk2) and non-activated forms of Cdk2 and/or cyclin A. Phosphorylation of residue
      Thr160 only slightly increases the thermal stability of Cdk2, and its binary
      complexes with cyclin A and p27-KID. The p27-KID/P-Cdk2/cyclin A or p27
      KID/Cdk2/cyclin A ternary complexes exhibited significantly higher thermal
      stabilities compared to the binary complexes (P-Cdk2/cyclin A or Cdk2/cyclin A).
      Differences in T(m) values between the binary and ternary complexes with P-Cdk2
      and Cdk2 were +25.9 and +20.4 degrees C, respectively. These results indicate
      that the ternary complex with phosphorylated Cdk2 is stabilized to a larger
      extent than the non-phosphorylated complex. The free energy of association
      (deltaG(A)) for formation of the two ternary complexes was more favorable than
      for the binary complexes, indicating that a significantly smaller population of
      free components existed when all three components were present. These data
      indicate that p27-KID, which is intrinsically disordered in solution, acts as a
      thermodynamic tether when bound within the ternary complexes. It is proposed that
      thermodynamic tethering may be a general phenomena associated with intrinsically
      unstructured proteins (IUPs) which often function by binding to multiple partners
      in multi-protein assemblies.

PMID- 16458086
TI  - Ten years of eosinophilic oesophagitis: small steps or giant leaps?

PMID- 16458087
TI  - Anti-ganglioside antibodies in coeliac disease with neurological disorders.
AB  - BACKGROUND: Anti-ganglioside antibodies have been described in sera of coeliac
      patients with peripheral neuropathy and cerebellar ataxia. AIMS: To investigate
      the correlation between anti-ganglioside antibodies and neurological involvement
      in coeliac disease before and after gluten-free diet. PATIENTS AND METHODS:
      Twenty-two untreated coeliac patients with neurological dysfunction and 30
      untreated coeliacs without neurological dysfunction, 20 patients with
      neurological disorders, 50 autoimmune disease and 20 blood donors were tested for
      anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked
      immunosorbent assay. RESULTS: IgG antibodies to at least one of the three
      antigens tested were positive in 64% of coeliac patients with neurological
      symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02),
      50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases
      (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet
      determined anti-ganglioside antibody disappearance in about half of coeliacs.
      CONCLUSIONS: A significant correlation between anti-ganglioside antibodies and
      neurological disorders in patients with an underlying coeliac disease has been
      found. Anti-ganglioside antibodies may represent a new immunological marker to
      identify neurological impairment in patients with coeliac disease.

PMID- 16458089
TI  - Long-term outcomes of photorefractive keratectomy for anisometropic amblyopia in
      children.

PMID- 16458090
TI  - Evaluation of Orbscan II corneal topography in individuals with myopia.
AB  - PURPOSE: To evaluate Orbscan II (Bausch & Lomb, Orbtek Inc., Salt Lake City, UT)
      corneal topography in individuals with myopia. DESIGN: Retrospective,
      observational, consecutive, clinical case series. PARTICIPANTS: One hundred forty
      eyes of 70 persons with myopia. METHODS: Manifest refraction results and the
      Orbscan II corneal topographic maps were reviewed retrospectively. MAIN OUTCOME
      MEASURES: Refractive powers and the following test indices produced by Orbscan II
      were analyzed: anterior elevation best-fit sphere (BFS), posterior elevation BFS,
      maximum posterior elevation (Max PE), radius of Max PE, maximum keratometry,
      minimum keratometry, astigmatism, 3-mm irregularity, 3-mm mean power, 3-mm
      astigmatism, 5-mm irregularity, 5-mm mean power, 5-mm astigmatism, corneal
      diameter, pupil diameter, thinnest pachymetry, and anterior chamber depth. The
      correlations between right eyes and left eyes and between indices were explored.
      RESULTS: Of the 140 eyes, the mean manifest refraction was -5.27+/-2.19 diopters
      (D; range, -10.50 to 0.00 D), the mean Max PE was 28+/-7 mum, and the mean
      maximum keratometry was 44.5+/-1.5 D. Correlation coefficient analyses of Orbscan
      II quantitative indices combined with pattern recognition showed that there were
      high degrees of correlations between the right and left eyes of each individual
      patient. Maximum posterior elevation, corneal irregularity, and thinnest
      pachymetry did not vary with the degree of maximum keratometry. CONCLUSIONS: This
      article provides a detailed description and analysis of Orbscan II corneal
      topography of a normal population with myopia. This helps in establishing normal
      standards in Orbscan II corneal topography that will aid in preoperative
      assessment in refractive surgery.

PMID- 16458091
TI  - Evidence for a learning effect in short-wavelength automated perimetry.
AB  - PURPOSE: To document the magnitude of any learning effect for short-wavelength
      automated perimetry (SWAP) in patients with either ocular hypertension (OHT) or
      open-angle glaucoma (OAG) who are experienced in standard automated perimetry
      (SAP). DESIGN: Experimental study. PARTICIPANTS: Thirty-five patients (22 with
      OHT and 13 with OAG) who had previously undergone at least 3 threshold SAP visual
      field examinations with the Humphrey Field Analyzer (HFA; Carl Zeiss Meditech
      Inc., Dublin, CA), and 9 patients with OHT who had not previously undertaken any
      form of perimetry. METHODS: Each patient attended for SWAP on 5 occasions, each
      separated by 1 week. At each visit, both eyes were examined using Program 24-2 of
      the HFA; the right eye was always examined before the left eye. MAIN OUTCOME
      MEASURES: (1) Change over the 5 examinations, in each eye, of the visual field
      indices Mean Deviation (MD), Short-term Fluctuation (SF), Pattern Standard
      Deviation (PSD), and Corrected Pattern Standard Deviation. (2) Change in each eye
      between Visits 1 and 5 in proportionate Mean Sensitivity (pMS) for the central
      annulus of stimulus locations compared with that for the peripheral annulus
      thereby determining the influence of stimulus eccentricity on any alteration in
      sensitivity. (3) Change between Visits 1 and 5 in the number and magnitude of the
      Pattern Deviation (PD) probability levels associated with any alteration in
      sensitivity. RESULTS: The MD, SF, and PSD each improved over the 5 examinations
      (each at P<0.001). The improvement in pMS between Visits 1 and 5 was greater for
      the peripheral annulus than for the central annulus by approximately twofold for
      the patients with OAG. Considerable variation was present between patients,
      within and between groups, in the number of locations exhibiting an improving
      sensitivity between Visits 1 and 5 by 1 or more PD probability levels.
      CONCLUSIONS: Care should be taken to ensure that, during the initial
      examinations, apparent field loss with SWAP in patients exhibiting a normal field
      by SAP is not the result of inexperience in SWAP. Apparently deeper or wider
      field loss in the initial examinations with SWAP compared with that exhibited by
      SAP in OAG also may arise from inexperience in SWAP.

PMID- 16458093
TI  - Evaluation of the clinical age-related maculopathy staging system.
AB  - OBJECTIVE: To evaluate a clinical classification system, the Clinical Age-Related
      Maculopathy Staging (CARMS) system, for age-related maculopathy (ARM) using a
      simple grading scale designed for clinical practice and clinical research
      protocols. PARTICIPANTS: Two hundred forty-six male and female participants with
      various stages of ARM who were enrolled during the first 4 years of a
      longitudinal study were selected for the evaluation of the CARMS system. DESIGN:
      Cross-sectional comparison study. METHODS: The CARMS system divides patients into
      5 mutually exclusive categories based on slit-lamp assessment of drusen, retinal
      pigment epithelial irregularities, geographic atrophy, retinal pigment epithelial
      detachment, and choroidal neovascularization. Fundus photographs and clinical
      data of the subjects were used to evaluate this scale. Clinical grades assigned
      for 492 eyes of 246 patients with varying stages of ARM were compared with grades
      obtained from photographs evaluated by a reading center. To compare grades
      obtained from an inexperienced grader with those of an experienced grader,
      observations based on photographs from 50 randomly selected patients were
      reviewed. To quantify intraobserver agreement for photographic grades,
      observations from one observer were compared with those made at a later date by
      the same observer. MAIN OUTCOME MEASURES: Reliability and validity of the CARMS
      system in grading various stages of ARM based on clinical examination and
      photography. RESULTS: The degree of overall agreement between the clinically
      assigned grade and photographic assessment for 492 eyes was substantial (exact
      overall agreement, 75%; unweighted kappa, 0.63; weighted kappa, 0.78). For
      advanced age-related macular degeneration, the sensitivity was 0.83, and
      specificity was 0.97. When assessing photographic grades, the degree of agreement
      between an inexperienced and an experienced grader was very high (unweighted
      kappa, 0.79; weighted kappa, 0.86), and the degree of intraobserver agreement was
      excellent (unweighted kappa, 0.92; weighted kappa, 0.97). CONCLUSIONS: The CARMS
      system, a 5-level clinical scale, is a valid and reliable staging system that can
      be used in both clinical practice and in clinical research protocols involving
      patients with all stages of ARM.

PMID- 16458092
TI  - Comparison of the effects of latanoprost, travoprost, and bimatoprost on
      circadian intraocular pressure in patients with glaucoma or ocular hypertension.
AB  - PURPOSE: To compare 24-hour reduction in intraocular pressure (IOP) by
      latanoprost 0.005%, travoprost 0.004%, and bimatoprost 0.03% in patients with
      primary open-angle glaucoma (POAG) or ocular hypertension (OH). DESIGN:
      Randomized, double-masked, crossover study. PARTICIPANTS: Twenty-four patients
      with POAG and 20 with OH. METHODS: Patients were treated with latanoprost,
      travoprost, and bimatoprost for 1 month. The treatment sequence was randomized,
      and washout lasted 30 days for each trial drug. Four 24-hour tonometric curves
      were recorded for each patient: 1 at baseline and 1 after each treatment period.
      MAIN OUTCOME MEASURES: Intraocular pressure was measured at 3, 6, and 9 am; noon;
      3, 6, and 9 pm; and midnight by 2 treatment-masked well-trained evaluators using
      a handheld electronic tonometer with the patient in supine and sitting positions
      and a Goldmann applanation tonometer with the patient sitting at the slit lamp.
      Supine systemic blood pressure was recorded at the same times. A randomized
      blocks analysis of variance was used to analyze data. RESULTS: All 3 drugs were
      highly effective in reducing IOP when compared to baseline. Mean IOP reductions
      were similar after the 3 prostaglandin analogs, and none of the differences among
      treatments reached statistical significance. The drugs' effect was significantly
      greater during the daytime (9 am-9 pm) than during the nighttime (midnight-6 am)
      with all prostaglandin analogs. In 7 of 44 patients (16%), nocturnal IOP was
      significantly higher than diurnal IOP, both at baseline and under the 3
      prostaglandin analogs. CONCLUSIONS: From a clinical point of view, the overall
      results seem to indicate that the 3 prostaglandin analogs are powerful agents in
      controlling round-the-clock IOP in POAG and OH patients.

PMID- 16458094
TI  - Analysis of the retinal nerve fiber layer after indocyanine green-assisted
      vitrectomy for idiopathic macular holes.
AB  - PURPOSE: To analyze retinal nerve fiber layer (RNFL) thickness in eyes with or
      without visual field (VF) defects after indocyanine green-assisted vitrectomy for
      idiopathic macular holes using optical coherence tomography (OCT) and to
      investigate the relationship between postoperative VF defects and RNFL damage.
      DESIGN: Retrospective interventional case series. PARTICIPANTS: Thirty-four eyes
      of 32 patients with idiopathic macular holes that underwent vitrectomy between
      January 2001 and March 2003 were included in this study. Eyes were divided into 3
      groups according to the occurrence of postoperative VF defects and the use of
      indocyanine green for internal limiting membrane peeling during surgery: 11 eyes
      with VF defects after indocyanine green-assisted vitrectomy (group 1), 9 eyes
      without VF defects despite the use of indocyanine green (group 2), and 14 eyes
      without VF defects that underwent vitrectomy without indocyanine green (group 3).
      METHODS: Retinal nerve fiber layer thickness in each of 4 quadrants (superior,
      inferior, nasal, temporal) was measured with OCT. MAIN OUTCOME MEASURE: Retinal
      nerve fiber layer thickness around the optic disc. RESULTS: The mean RNFL
      thickness in 3 of 4 quadrants (superior, nasal, inferior) in group 1 was
      significantly less than that in the corresponding quadrant in groups 2 and 3
      (P<0.01). In the temporal quadrant, there was a significant difference between
      groups 1 and 3 (P = 0.02), but not between groups 1 and 2. The RNFL thickness in
      group 1 was significantly less in 3 quadrants in operated eyes than in fellow
      eyes (P<0.05). CONCLUSIONS: The RNFL thickness was reduced in eyes with VF
      defects after indocyanine green-assisted vitrectomy for macular holes, suggesting
      that the postoperative VF defects may have been caused by RNFL damage relating to
      the use of indocyanine green.

PMID- 16458095
TI  - Ophthalmic findings in Apert's syndrome after craniofacial surgery: twenty-nine
      years' experience.
AB  - PURPOSE: To survey the spectrum of ophthalmic morbidity in Apert's syndrome after
      craniofacial surgery. DESIGN: A retrospective study of patients with Apert's
      syndrome managed at the Australian Craniofacial Unit from 1975 to 2004.
      PARTICIPANTS: Sixty-one patients (31 females and 30 males) had final ophthalmic
      reviews at a mean age of 9.3 years (standard deviation, 9.2; range, 0.2-48.3;
      median, 8.2 years). METHODS: Patients were identified from the unit database, and
      case notes were reviewed. Cases that had < or =2 recorded variables were
      excluded. Demographic details, age at last ophthalmic review, and total
      craniofacial operations performed were documented. MAIN OUTCOME MEASURES: Best
      corrected visual acuity, cycloplegic refractions, strabismus, amblyopia, corneal
      abnormality, fundoscopic findings, and visually evoked potentials. RESULTS: The
      average number of craniofacial operations performed was 2 (range, 1-4; median,
      2). Visual impairment was found in 54% of patients in at least one eye and in 19%
      of patients in their better eye. The most common cause was amblyopia, with a
      prevalence of 35%. Optic atrophy caused visual impairment in 5% of patients and
      corneal scarring in 8%. Sixty-three percent of patients had strabismus with more
      esotropia than exotropia. Ametropia was found in 69% of patients (42% were
      hypermetropic and 27% were myopic). Anisometropia of > or =0.75 diopters was
      present in 16 cases (50%). CONCLUSIONS: Visual impairment is a common finding in
      Apert's syndrome and amblyopia is the major cause. Ametropia, astigmatism,
      anisometropia, and strabismus frequently occur in patients with Apert's syndrome
      at final ophthalmic review. Although optic atrophy was the major cause of visual
      loss in the era prior to craniofacial surgery, the prevalence of optic atrophy is
      low since the adoption of current surgical protocols. Corneal damage also
      contributed toward visual impairment. Early detection and adequate management of
      amblyopia, timely decompressive surgery before the presence of optic atrophy, and
      protection of the cornea should be the management goals of ophthalmologists in
      craniofacial units managing these patients.

PMID- 16458097
TI  - Phaco vs. small-incision.

PMID- 16458098
TI  - Injections for chalazia?

PMID- 16458100
TI  - Injections for chalazia?

PMID- 16458101
TI  - Injections for chalazia?

PMID- 16458104
TI  - Mitomycin C in highly myopic eyes.

PMID- 16458107
TI  - IOP after triamcinolone acetonide.

PMID- 16458108
TI  - Safe and effective?

PMID- 16458110
TI  - Herceptin: mechanisms of action and resistance.
AB  - HER-2 is overexpressed in 20-25% of invasive breast cancers and is associated
      with an aggressive tumor phenotype and reduced survival rate. The HER-2 status of
      a tumor is the critical determinant of response to the HER-2-targeted antibody
      Herceptin. Thus, accurate assessment of HER-2 expression levels is essential for
      identifying breast cancer patients who will benefit from HER-2-targeted therapy.
      Herceptin combined with chemotherapy increases response rates, time to disease
      progression, and survival. However, the majority of cancers that initially
      respond to Herceptin begin to progress again within 1 year. This review describes
      mechanisms by which Herceptin inhibits cell growth in breast cancers that
      overexpress HER-2 and highlights possible mechanisms contributing to Herceptin
      resistance.

PMID- 16458111
TI  - Histone deacetylase inhibitors require caspase activity to induce apoptosis in
      lung and prostate carcinoma cells.
AB  - Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic
      agents with the capacity to induce growth arrest and/or apoptosis of cancer
      cells. However, their precise mechanism of action is uncertain; particularly, the
      role of caspases in the apoptotic response to HDIs is controversial. Here, we
      show that the HDIs explored, suberoylanilide hydroxamic acid, sodium butyrate and
      trichostatin A, activated caspase-3 in A549 and PC-3 carcinoma cells.
      Additionally, the poly-caspase inhibitor z-VAD-fmk prevented HDI-induced
      apoptosis, as judged by determining mitochondrial membrane potential and by
      quantifying internucleosomal DNA fragmentation. Importantly, z-VAD-fmk also
      significantly inhibited HDI-elicited cell death, as assessed by measuring
      propidium iodide uptake. As an accessory finding, with the inhibition of
      caspases, a HDI-induced G2-M arrest became evident. Taken together, these results
      provide evidence that HDIs require activated caspases to induce apoptosis of
      carcinoma cells.

PMID- 16458112
TI  - Proteasome inhibitor PSI induces apoptosis in human mesothelioma cells.
AB  - Malignant mesothelioma is an increasingly common tumor with an almost 100%
      mortality rate. It is refractory to conventional treatment. We have previously
      shown with SSH and microarray that the mRNA expression level of proteasome is
      higher in epithelioid mesothelioma cell lines than in sarcomatoid ones. This
      study evaluates the differential apoptotic effect of proteasome inhibitors on
      both of these mesothelioma sub-lines. Proteasome inhibitors show substantial anti
      tumor activity in some tumor cells in vitro and in vivo, but the effects on
      mesothelioma cells has not been studied. The viability of mesothelioma cells was
      reduced in a dose- and time-dependent manner by the proteasome inhibitors tested;
      PSI was effective with a low dose, but higher concentrations were needed for
      calpain inhibitor I. The epithelioid mesothelioma cells are more sensitive to the
      inhibitors than the sarcomatoid ones, their IC50 after 24 h of treatment with PSI
      being 4 and 16 microm, respectively. Other mesothelioma cell lines show similar
      sensitivity. PSI seemed to decrease mesothelioma viability by inducing apoptosis,
      as verified by cell morphology, Western blotting analysis of caspase 3 cleavage,
      and flow-cytometric analysis. In conclusion, PSI, a representative agent that
      reduces viability and induces apoptosis of mesothelioma cells, might be useful in
      the treatment of patients with mesothelioma, especially of epithelioid phenotype.

PMID- 16458113
TI  - Elevation of cyclin B1, active cdc2, and HuR in cervical neoplasia with human
      papillomavirus type 18 infection.
AB  - Over 30 cervical epitheliotrophic HPV types may lead to altered biological
      functions that affect the clinical outcome of HPV infection. In order to
      determine the regulatory mechanism and effect of different HPV subtypes, we
      performed functional assays on cdc2, cyclinB1 and HuR in human uterine cervical
      samples. After confirming 22 HPV types among 95 cervical swabs, 10 cervical
      tissues, and seven established cell lines using a DNA chip, we evaluated the
      functional activities of G2 molecules assays, that included; western blotting for
      cyclin B1, cdc2 and phospho-cdc2 (Y15 and T161), immunoprecipitation for cdc2, a
      nuclear extraction fractional assay, and RT-PCR for cyclin B1. The expression of
      cyclin B1 was found to be dependent on HPV type, and was particularly
      overexpressed in high-risk types, whereas cdc2 was ubiquitously expressed
      irrespective of HPV type. Phospho-cdc2 and cyclin B1, however, were most intense
      in HPV18 infected cervical samples. Furthermore, the HuR stabilizing factor of
      the cyclin B1 transcript was upregulated in HPV 18 infected swabs. Moreover, SiHa
      cell line showed weaker G2 functional activity than the HeLa cell line. This
      study demonstrates that HPV-18 decreases the fidelity of mitotic checkpoints and
      increases cdc2-associated histone H1 kinase activity relative to control
      populations, and further shows that the G2 checkpoint is aberrant by virtue of
      the stabilization of cyclin B1 mRNA through the upregulation of HuR protein and
      the functional form of cdc2, especially in cases with HPV 18 infected cervical
      lesions.

PMID- 16458114
TI  - Bcl-2 switches the type of demise from apoptosis to necrosis via cyclooxygenase-2
      upregulation in HeLa cell induced by hydrogen peroxide.
AB  - Bcl-2 is best known for its anti-apoptotic function in a wide variety of cell
      types. The objective of this study was to investigate the effects of bcl-2 on the
      types of cell demise in the HeLa/bcl-2 cells induced by H2O2. The HeLa cell
      expressed stably bcl-2 was established and defined as the HeLa/bcl-2 cell strain,
      while the cell transfected with the empty expression vector was defined as the
      HeLa/vector cell strain. MTT assay revealed that the HeLa/bcl-2 cells showed a
      shorter life span. BrdU incorporation assay indicated that the bcl-2 exerted anti
      demise effect on the HeLa/bcl-2 cells at the low concentration of H2O2. However,
      at the high concentration of H2O2, the death of the HeLa/bcl-2 cells was more
      than that of the HeLa/vector cells. The flow cytometry demonstrated that H2O2
      mainly induced apoptosis in the HeLa/vector cells and elicited necrosis in the
      HeLa/bcl-2 cells. The addition of celecoxib to the cells treated by H2O2 could
      increase apoptosis in the HeLa/vector cells and convert necrosis into apoptosis
      in the HeLa/bcl-2 cells. The higher levels of cellular free radical and GSH were
      found in the HeLa/bcl-2 cells, but not in the HeLa/vector cells. With 200 microM
      H2O2 challenge for 48 h, the level of the cellular free radical was increased in
      the both strains, while the level of the GSH was decreased in the both strains.
      Celecoxib could reverse the difference between the both strains led by H2O2.
      Western blotting showed that the expression of COX-2 was always higher in the
      HeLa/bcl-2 cells than in the HeLa/vector cells under the both of treated and
      untreated with H2O2, while the level of COX-1 was relative stable in the both
      strains. These results suggested that the crosstalk between the bcl-2 and the COX
      2 pathways could exist, the bcl-2 might up-regulate COX-2 to modify sensitivity
      to the types of demise in the HeLa/bcl-2 cell.

PMID- 16458115
TI  - siRNA targeting LMP1-induced apoptosis in EBV-positive lymphoma cells is
      associated with inhibition of telomerase activity and expression.
AB  - Epstein-Barr Virus (EBV) is closely associated with B cell malignancies. However,
      whether EBV appears to be absolutely required for cell proliferation and survival
      in lymphoma cells is still unknown. In this study, small interfering RNA (siRNA)
      targeting LMP1 was employed to investigate the effect of LMP1 on cell
      proliferation in EBV-positive lymphoblastoid B-cell line. A plasmid stable
      encoding 21-nt small RNA specifically and efficiently interfering LMP1 was
      constructed, resulting in a substantial loss of LMP1 mRNA and a significantly
      decreased LMP1 protein expression. Our data demonstrated that cell proliferation
      was completely inhibited and apoptosis was induced after knockdown of LMP1 gene
      in lymphoblastoid B-cell line. Also, we found that suppression of LMP1 caused
      downregulation of telomerase protein expression and decreased telomerase activity
      in lymphoma cells. In EBV-negative NPC cell line, transfection of plasmid
      expressing LMP1 greatly enhanced telomerase protein expression. Our results
      suggested that siRNA targeting LMP1 can induce apoptosis in EBV-positive lymphoma
      cells and is associated with inhibition of telomerase activity and expression.
      siRNA-directed LMP1 silencing may be of the therapeutic value for preventing and
      treating those EBV-associated tumors.

PMID- 16458116
TI  - Inhibition of cell growth and induction of G1-phase cell cycle arrest in hepatoma
      cells by steroid extract from Meretrix meretrix.
AB  - In this study, we report that the steroid extract 5alpha, 8alpha-epidioxycholest
      6-ene-3beta-ol (MME) from Meretrix meretrix has the ability to inhibit growth of
      hepatoma cells and to induce G1-phase cell cycle arrest in two human hepatoma
      cell lines, HepG2 and Hep3B. HepG2 cells were more sensitive than Hep3B to MME.
      The extract markedly up-regulated the expression of p53 and p21WAF1/CIP1 in
      HepG2, suggesting that MME-induced G1 phase cell cycle arrest in HepG2 might be
      p53-dependent. Therefore, the up-regulation of p27KIP1and p16INK4A in both cell
      lines indicates that a p53-independent pathway might be involved in the mechanism
      of MME inducing cell cycle arrest. In conclusion, MME induces G1 phase cell cycle
      arrest via both p53-dependent and p53-independent pathways.

PMID- 16458117
TI  - Synergistic and tumour selective effects of chemotherapy and ultrasound
      treatment.
AB  - In the present work, we have analysed the effects of low frequency ultrasound
      exposure in combination with liposomally encapsulated doxorubicin (Caelyx) and
      Plurogel encapsulated fluorouracil (5-FU) on 144 Balb/c nude mice inoculated with
      a WiDr (human colon cancer) tumour cell line, at various concentrations.
      Furthermore, the theoretical foundation for the effects of ultrasound exposure of
      tissues and organs, and for its interaction with and enhancement of controlled
      release of encapsulated anticancer drugs are outlined. For the first time, it is
      shown that non-hyperthermic ultrasound treatment significantly increases the
      effect of liposomally encapsulated cytostatic drugs on tumour growth. Synergetic
      effects were larger for low drug concentrations, indicating that the approach may
      benefit patients for whom chemotherapeutic treatment gives limited effect, or for
      whom drug concentrations have to be restricted due to general health
      considerations.

PMID- 16458118
TI  - Petrotetrayndiol A induces cell cycle arrest and apoptosis in SK-MEL-2 human
      melanoma cells through cytochrome c-mediated activation of caspases.
AB  - We investigated the possible mechanisms by which petrotetrayndiol A, a
      polyacetylene from the sponge Petrosia sp., exerts its anti-proliferative
      activity in cultured SK-MEL-2 human melanoma cells. Petrotetrayndiol A-treated SK
      MEL-2 cells showed growth inhibition and induction of apoptosis in a dose
      dependent manner as measured by MTT assay, fluorescent microscopy and flow
      cytometric analysis. Flow cytometric analysis revealed that petrotetrayndiol A
      resulted in G2/M arrest in the cell cycle progression which was associated with a
      marked decrease in the protein expression of cyclin B1 and its activating partner
      Cdc2 with concomitant inductions of p21WAF1/CIP1. The increase in apoptosis was
      associated with a dose-dependent up-regulation of cytosolic factor, such as Bax
      and release of cytochrome c, and down-regulation of Bcl-2. We also observed
      activation of caspase-9 and caspase-3, DNA ladder formation, proteolytic
      degradation of poly(ADP-ribose)-polymerase (PARP), and selective down-regulation
      of cIAP-1. The apoptotic manifestations, such as PARP cleavage and DNA
      fragmentation, were abolished in the presence of the tripeptide caspase inhibitor
      z-VAD-fmk and a caspase-3-specific inhibitor Ac-DEVD-cho. Our data thus
      demonstrate that petrotetrayndiol A-induced apoptosis and growth inhibition of SK
      MEL-2 cells is dependent on caspase activation.

PMID- 16458119
TI  - Alpha-tocopheryl succinate alters cell cycle distribution sensitising human
      osteosarcoma cells to methotrexate-induced apoptosis.
AB  - alpha-Tocopheryl succinate (alpha-TOS) exerts pleiotrophic responses in malignant
      cells leading to cell cycle arrest, differentiation and apoptosis. We tested the
      ability of alpha-TOS to induce apoptosis or cell cycle perturbation in three
      human osteosarcoma (OS) cell lines which differ in their pRB and p53 status. We
      found high levels of apoptosis in OS cells carrying wild-type p53 gene when
      exposed to alpha-TOS, while the mutant p53 cells were resistant. A S/G2
      transition arrest was observed in two OS cell lines exposed to alpha-TOS, which
      sensitised them to methotrexate, an agent whose activity is cell cycle-dependent.
      We propose that alpha-TOS may be used as a drug or an adjuvant for treatment of
      osteosarcomas.

PMID- 16458120
TI  - Chronic renal failure rats are highly sensitive to aristolochic acids, which are
      nephrotoxic and carcinogenic agents.
AB  - Aristolochic acid (AA), a component of some Chinese herbal medicines, may cause
      Chinese Herbs Nephropathy (CHN) and multi-systemic tumors by the formation of AA
      DNA adducts. In this study, we established an animal model to further
      characterize the mechanisms of AA-induced diseases. Our results indicated that AA
      significantly inhibited rat growth in terms of weight gain. By measuring the
      serum creatinine levels, AA resulted in considerable damage to the rat renal
      system, not only for those in which chronic renal failure (CRF) was induced but
      also for normal healthy rats. Mutation-specific polymerase chain reaction (PCR)
      and XbaI restriction fragment length polymorphism (RFLP) revealed the CAA-->CTA
      transversion mutation at codon 61 of the H-ras proto-oncogene from the stomach
      tissues of CRF rats fed with AA, but not from other tissues of rats in the same
      experimental group. In addition, no such mutations were found in the tissues of
      CRF rats without AA treatment or healthy rats fed with AA. Our results strongly
      demonstrated that AA was in fact nephrotoxic and carcinogenic, especially to
      those CRF rats.

PMID- 16458121
TI  - Chemosensitization of bladder cancer cells by survivin-directed antisense
      oligodeoxynucleotides and siRNA.
AB  - Survivin is known to be overexpressed in numerous tumor types including human
      bladder cancer and to cause resistance to radiation and chemotherapy. Therefore,
      we tested the antisense oligodeoxynucleotide AS-SVV286 and the small interfering
      RNA si-SVV284 to down-regulate survivin in the BCa cell lines EJ28 and 5637
      thereby acting as sensitizers for chemotherapy. Pretreatment with these
      inhibitors followed by chemotherapy caused an enhanced decrease in cell
      viability. The observed reduction in cell counts associated with increased rates
      of apoptosis paralleled the degree of reduction of survivin expression that was
      achieved more efficiently by the siRNA than by the AS-ODN. Nevertheless, both
      therapy approaches in combination with all tested chemotherapeutics provoked a
      remarkable inhibition of viability and may serve as suitable additive tools for
      chemosensitization of bladder cancer cells.

PMID- 16458123
TI  - Lack of modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) rat
      hepatocarcinogenesis by caffeine, a CYP1A2 inducer, points to complex
      counteracting influences.
AB  - 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), one of the most abundant
      carcinogenic heterocyclic amines in cooked foods, is speculated to be a human
      liver carcinogen. To test the hypothesis that it is metabolically activated by
      CYP1A2, we here investigated the effects of caffeine as a CYP1A2 inducer on MeIQx
      induced rat hepatocarcinogenesis in a medium-term liver bioassay system.
      Unexpectedly, no modifying effects of caffeine on MeIQx-induced
      hepatocarcinogenesis were evident, although up-regulation of CYP1A2 and NAT2 were
      detected. Therefore, mRNAs extracted from GST-P positive foci and the surrounding
      liver tissue in each group were analyzed to explore mechanisms in detail. The
      results suggest that suppression of syndecan-2 (Sdc2) and induction of cell cycle
      arrest through a p21-dependent pathway might have counter-acted any promotion
      effects of up-regulation of CYP1A2.

PMID- 16458122
TI  - Expression of Etk/Bmx tyrosine kinase in the tumorigenicity of nasopharyngeal
      epithelium and its relation with EB virus infection and the apoptosis-related
      protein Bcl-2.
AB  - We compared Etk/Bmx expression in nasopharyngeal carcinoma (NPC) and non
      neoplastic nasopharyngeal lesions in order to learn whether the expression of
      this non-receptor protein tyrosine kinase is associated with the development of
      NPC. We also related Etk/Bmx expression to factors resulting from Epstein-Barr
      virus (EBV) infection. We used immunohistochemistry (IHC) and in situ
      hybridization to examine 20 non-neoplastic nasopharyngeal lesions and 49 cases of
      NPC to assess Etk/Bmx, EB virus latent membrane protein-1 (LMP-1), Bcl-2 and EBV
      encoded small RNA-1 expression in these samples. Etk/Bmx expression was present
      in the basal cell nuclei of the nasopharyngeal epithelium in 1/9 (11.1%) cases of
      chronic nasopharyngitis and 2/11 cases (18.2%) of dysplasia. While 13/49 (26.5%)
      NPC cases expressed Etk/Bmx, the difference in frequency between the expression
      of Etk/Bmx in the non-neoplastic and NPC cases was not significant. Etk/Bmx
      expression was correlated with the presence of EBER-1 immunopositivity in
      dysplasia and in NPC but not in chronic nasopharyngitis. The presence of Etk/Bmx
      immunopositivity was independent of the expression of either LMP-1 or Bcl-2 in
      either the nasopharyngeal carcinoma or the non-neoplastic lesions. This suggests
      that in some cases of non-neoplastic and neoplastic nasopharyngeal lesions,
      Etk/Bmx may participate in regulating epithelial differentiation. While EBV
      related small RNA-1 may participate in this regulation, neither LMP-1 or Bcl-2
      expression appears to be related to Etk/Bmx expression.

PMID- 16458124
TI  - Microbiologic characterization of isolates from a dalbavancin clinical trial for
      catheter-related bloodstream infections.
AB  - Dalbavancin, a new-generation semisynthetic lipoglycopeptide in phase 3 clinical
      development, has been documented to be more active than vancomycin or teicoplanin
      against Gram-positive bacteria, including multidrug-resistant strains, by in
      vitro testing and in animal models. The human pharmacokinetics of dalbavancin
      predicts efficacy at weekly dosing intervals. In a phase 2 open-label clinical
      trial, dalbavancin exhibited superiority when compared with vancomycin against
      catheter-related bloodstream infection (CR-BSI). The majority of pathogens
      identified in this study as in clinical practice were coagulase-negative
      staphylococci (CoNS), necessitating rigorous characterization of duplicate
      isolates to rule out contaminants and to validate cases for study evaluations. At
      follow-up for the intent-to-treat population, overall pathogen eradication was
      92.3% for dalbavancin and 75.9% for vancomycin. We describe the details of
      organisms isolated, their epidemiologic/genetic characterization, susceptibility
      patterns against glycopeptides, and the eradication rates by organism group. In
      conclusion, dalbavancin was active against all isolated pathogens associated with
      CR-BSI (CoNS, Staphylococcus aureus and Enterococcus faecalis; all MIC results, <
      or = 0.25 microg/mL) and achieved significant (P < 0.05) clinical success when
      compared with vancomycin.

PMID- 16458125
TI  - Pre-hospital 12-lead electrocardiography programs: a call for implementation by
      emergency medical services systems providing advanced life support--National
      Heart Attack Alert Program (NHAAP) Coordinating Committee; National Heart, Lung,
      and Blood Institute (NHLBI); National Institutes of Health.
AB  - Emergency medical services (EMS) providers who administer advanced life support
      should include diagnostic 12-lead electrocardiography programs as one of their
      services. Evidence demonstrates that this technology can be readily used by EMS
      providers to identify patients with ST-segment elevation myocardial infarction
      (STEMI) before a patient's arrival at a hospital emergency department. Earlier
      identification of STEMI patients leads to faster artery-opening treatment with
      fibrinolytic agents, either in the pre-hospital setting or at the hospital.
      Alternatively, a reperfusion strategy using percutaneous coronary intervention
      can be facilitated by use of pre-hospital 12-lead electrocardiography (P12ECG).
      Analysis of the cost of providing this service to the community must include
      consideration of the demonstrated benefits of more rapid treatment of patients
      with STEMI and the resulting time savings advantage shown to accompany the use of
      P12ECG programs.

PMID- 16458126
TI  - Targeting cholesteryl ester transfer protein for the prevention and management of
      cardiovascular disease.
AB  - Epidemiologic studies have shown that the concentration of high-density
      lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of
      coronary heart disease risk. This identifies HDL-C as a potential therapeutic
      target. Compared with low-density lipoprotein cholesterol (LDL-C)-lowering
      agents, however, currently available HDL-raising drugs are relatively
      ineffective. Consequently, recent years have seen considerable efforts expended
      on identifying new drugs that can raise HDL-C. Cholesteryl ester transfer protein
      (CETP) plays an important role in cholesterol metabolism, being responsible for
      the transfer of cholesteryl esters from HDL to very low-density lipoproteins and
      LDLs. The observation that Japanese populations with CETP deficiency exhibited
      high levels of HDL-C has led to the concept that drugs targeting CETP activity
      may elevate HDL-C levels and potentially decrease cardiovascular risk. Support of
      this proposition has been obtained in rabbits where inhibition of CETP activity
      is markedly antiatherogenic. Two CETP inhibitors-torcetrapib and JTT-705-are
      currently in the preliminary stages of clinical development. Initial studies with
      these drugs in humans show that they substantially increase HDL-C levels and
      modestly decrease LDL-C levels. Larger, long-term, randomized, clinical end point
      trials are required to determine whether the beneficial effects of CETP
      inhibitors on lipoprotein metabolism can translate into reductions in
      cardiovascular events.

PMID- 16458127
TI  - Diastolic heart failure can be diagnosed by comprehensive two-dimensional and
      Doppler echocardiography.
AB  - There are many myocardial and non-myocardial conditions that cause heart failure
      with normal left ventricular ejection fraction (LVEF). Among them, diastolic
      heart failure (heart failure due to diastolic dysfunction) is the most common
      cause of heart failure with normal LVEF. Diastolic heart failure easily can be
      diagnosed by comprehensive two-dimensional and Doppler echocardiography, which
      can demonstrate abnormal myocardial relaxation, decreased compliance, and
      increased filling pressure in the setting of normal LV dimensions and preserved
      LVEF. Therefore, diastolic heart failure should always be considered when LVEF is
      normal on two-dimensional echocardiography in patients with clinical evidence of
      heart failure. The diagnosis can be confirmed if Doppler echocardiography and
      myocardial tissue imaging provide evidence for impaired myocardial relaxation
      (i.e., decreased longitudinal velocity of the mitral annulus during early
      diastole and decreased propagation velocity mitral inflow), decreased compliance
      (shortened mitral A-wave duration and mitral deceleration time), and increased
      filling pressure (shortened isovolumic relaxation time and an increased ratio
      between early diastolic mitral and mitral annular velocities). Early
      identification of diastolic dysfunction in asymptomatic patients by the use of
      echocardiography may provide an opportunity to manage the underlying etiology to
      prevent progression to diastolic heart failure.

PMID- 16458128
TI  - Sirolimus-eluting versus paclitaxel-eluting stent implantation for the
      percutaneous treatment of left main coronary artery disease: a combined RESEARCH
      and T-SEARCH long-term analysis.
AB  - OBJECTIVES: The purpose of this study was to investigate the long-term clinical
      and angiographic profile of sirolimus-eluting stent (SES) versus paclitaxel
      eluting stent (PES) in patients undergoing percutaneous intervention for left
      main (LM) coronary disease. BACKGROUND: The long-term clinical and angiographic
      impact of SES as opposed to PES implantation in this subset of patients is
      unknown. METHODS: From April 2002 to March 2004, 110 patients underwent
      percutaneous intervention for LM stenosis at our institution; 55 patients were
      treated with SES and 55 with PES. The two groups were well balanced for all
      baseline characteristics. RESULTS: At a median follow-up of 660 days (range 428
      to 885), the cumulative incidence of major adverse cardiovascular events was
      similar (25% in the SES group vs. 29%, in the PES group; hazard ratio 0.88 [95%
      confidence interval 0.43 to 1.82]; p = 0.74), reflecting similarities in both the
      composite death/myocardial infarction (16% in the SES group and 18% in the PES
      group) and target vessel revascularization (9% in the SES group and 11% in the
      PES group). Angiographic in-stent late loss (mm), evaluated in 73% of the SES
      group and in 77% of the PES group, was 0.32 +/- 74 in the main and 0.36 +/- 0.59
      in the side branch in the SES group vs. 0.46 +/- 0.57 (p = 0.36) and 0.52 +/-
      0.42 (p = 0.41) in the PES group, respectively. CONCLUSIONS: In consecutive
      patients undergoing percutaneous LM intervention, PES may perform closely to SES
      both in terms of angiographic and long-term clinical outcome.

PMID- 16458129
TI  - Initial experience with a magnetic navigation system for percutaneous coronary
      intervention in complex coronary artery lesions.
AB  - OBJECTIVES: The aim of this study was to evaluate the feasibility of a magnetic
      assisted navigation system during percutaneous coronary intervention (PCI) of
      tortuous and severely angulated coronary arteries. BACKGROUND: The magnetic
      navigation system consists of two 0.8-T permanent magnets which generate a
      magnetic field over the heart. Altering the magnetic vector deflects a coronary
      guidewire with a magnetic tip. METHODS: Patients were selected for magnetic
      assisted intervention (MAI) for potentially difficult to cross lesions. The time
      required for placement of the guidewire, total procedure time, fluoroscopy time,
      and amount of contrast for the procedure were recorded. There were a total of 59
      patients undergoing PCI of 68 lesions. RESULTS: Patients were grouped based on
      whether MAI was attempted as a first option ("primary attempt"; n = 46) or
      following failure to pass a conventional guidewire ("secondary attempt"; n = 13).
      The target lesion was successfully crossed in 49 of 55 lesions (89%) and 9 of 13
      lesions (69%) in patients undergoing primary and secondary attempts,
      respectively. The procedural success rates were 84% and 62%, respectively. Most
      lesions were located in the circumflex artery territory (39% and 62% of lesions,
      respectively). The median (25th and 75th percentiles) time for crossing the
      lesion was longer in the secondary attempt group (14.8 [5, 15.5] vs. 28.9 [8, 38]
      min). Median fluoroscopy time and median contrast used were also higher among the
      secondary attempt group. CONCLUSIONS: This first report of MAI suggests that it
      may become a useful adjunct for wire placement in difficult coronary
      interventions.

PMID- 16458130
TI  - Randomized comparison of upstream tirofiban versus downstream high bolus dose
      tirofiban or abciximab on tissue-level perfusion and troponin release in high
      risk acute coronary syndromes treated with percutaneous coronary interventions:
      the EVEREST trial.
AB  - OBJECTIVES: We aimed to compare the effects of upstream tirofiban versus
      downstream high-dose bolus (HDB) tirofiban and abciximab on tissue level
      perfusion and troponin I release in high-risk non-ST-segment elevation acute
      coronary syndrome (ACS) patients treated with percutaneous coronary intervention
      (PCI). BACKGROUND: Optimal timing and dosage of glycoprotein IIb/IIIa inhibitors
      for ACS remain to be explored. METHODS: We randomized 93 high-risk ACS patients
      undergoing PCI to receive upstream (in the coronary care unit) tirofiban,
      downstream (just prior to PCI) HDB tirofiban, and downstream abciximab. We
      evaluated the effects of the three drug regimens on tissue-level perfusion using
      the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count, the TIMI
      myocardial perfusion grade (TMPG), and intracoronary myocardial contrast
      echocardiography (MCE) before and immediately after PCI and after cardiac
      troponin I (cTnI). RESULTS: The TMPG 0/1 perfusion was significantly less
      frequent with upstream tirofiban compared with HDB tirofiban and abciximab both
      before (28.1% vs. 66.7% vs. 71%, respectively; p = 0.0009) and after PCI (6.2%
      vs. 20% vs. 35.5%, respectively; p = 0.015). Upstream tirofiban was also
      associated with a significantly higher MCE score index (0.88 +/- 0.18 vs. 0.77 +/
      0.32 vs. 0.71 +/- 0.30, respectively; p < 0.05). Post-procedural cTnI elevation
      was significantly less frequent among patients in the upstream tirofiban group
      compared with the HDB tirofiban and abciximab groups (9.4% vs. 30% vs. 38.7%,
      respectively; p = 0.018). The cTnI levels after PCI were significantly lower with
      upstream tirofiban compared with HDB tirofiban (3.8 +/- 4.1 vs. 7.2 +/- 12; p =
      0.015) and abciximab (3.8 +/- 4.1 vs. 9 +/- 13.8; p = 0.0002) CONCLUSIONS: Among
      high-risk non-ST-segment-elevation ACS patients treated with an early invasive
      strategy, upstream tirofiban is associated with improved tissue-level perfusion
      and attenuated myocardial damage.

PMID- 16458131
TI  - The role of risk stratification in the decision to provide upstream versus
      selective glycoprotein IIb/IIIa inhibitors for acute coronary syndromes: a cost
      effectiveness analysis.
AB  - OBJECTIVES: We endeavored to determine under what conditions a strategy of
      upstream use of small molecule platelet glycoprotein (GP) IIb/IIIa inhibitors for
      all acute coronary syndromes (ACS) patients is cost effective compared to that of
      selective use of abciximab in only those patients requiring percutaneous coronary
      intervention (PCI). BACKGROUND: Small molecule GP IIb/IIIa inhibitors have shown
      benefit in ACS, but abciximab, the more expensive GP IIb/IIIa inhibitor, may be
      more effective during PCI. However, abciximab does not have proven efficacy in
      medical management. No prior study has attempted to balance these competing
      benefits. METHODS: A decision analysis was performed to examine two strategies:
      1) treat all ACS patients upstream with a small molecule GP IIb/IIIa inhibitor
      and continue through medical management and PCI, if performed; or 2) wait, and
      selectively use abciximab only in patients who ultimately undergo PCI. Applicable
      randomized controlled trial data were used for the principal analysis. RESULTS:
      The strategy of upstream use of a small molecule GP IIb/IIIa inhibitor was
      superior to selective use, and economically acceptable, with a cost-effectiveness
      ratio of 18,000 dollars per year of life gained. The superiority of the upstream
      use strategy persisted over the majority of sensitivity analyses. When stratified
      by risk according to Thrombolysis in Myocardial Infarction risk score, a strategy
      of upstream use was only cost effective in those patients with moderate or high
      risk. CONCLUSIONS: Upstream use of small molecule GP IIb/IIIa inhibition in ACS
      patients with moderate or high risk for cardiovascular events is a cost-effective
      approach that should be considered in this subset of patients.

PMID- 16458132
TI  - Upstream/downstream glycoprotein IIb/IIIa in non-ST-segment elevation myocardial
      infarction.

PMID- 16458133
TI  - Effect of platelet antigen polymorphism on platelet inhibition by aspirin,
      clopidogrel, or their combination.
AB  - OBJECTIVES: We studied the modifier effect of platelet antigen polymorphism
      (PlA2) on platelet inhibition by acetylsalicylic acid (ASA, i.e., aspirin),
      clopidogrel, or their combination in patients with coronary heart disease.
      BACKGROUND: Clopidogrel, when administered with ASA, was shown to significantly
      improve the outcome of patients with acute coronary syndromes compared with
      patients receiving only ASA. We have shown previously that the effect of ASA on
      platelets is modified by the glycoprotein IIIa single nucleotide polymorphism
      PlA2. Hence, an important pharmacogenetic question remains whether the
      antiplatelet effect of clopidogrel is uniform for all patients or, like
      acetylsalicylic acid, more selective. METHODS: Thirty PlA1/A1 and 30 PlA1/A2
      patients were assigned randomly to ASA 325 mg/day, clopidogrel 75 mg/day, or
      both. After 10 days, platelet function was studied. RESULTS: Clopidogrel provided
      stronger platelet inhibition than ASA with adenosine diphosphate as the agonist,
      and combination therapy resulted in greater inhibition than either inhibitor used
      alone (p < 0.0001). The use of ASA resulted in greater inhibition compared with
      clopidogrel with epinephrine (p < 0.0001) and collagen as agonists (p < 0.0001).
      With collagen as the agonist, platelets from PlA1/A2 donors were markedly and
      significantly less inhibited by ASA (p = 0.005). In contrast, with clopidogrel,
      no significant difference could be detected between inhibition of Pl(A1/A1) and
      Pl(A1/A2) platelets. CONCLUSIONS: The combination of ASA and clopidogrel appears
      superior to either agent alone in inhibiting platelet function. Pl(A2) functions
      as an important modifier for platelet responsiveness to ASA but not to
      clopidogrel. These findings could have significant impact on the future design of
      pharmacogenetic antithrombotic strategies for patients with coronary heart
      disease.

PMID- 16458134
TI  - Predictors of adverse outcome among patients with hypertension and coronary
      artery disease.
AB  - OBJECTIVES: We sought to determine predictors for adverse outcomes in
      hypertensive patients with coronary artery disease (CAD). BACKGROUND: Factors
      leading to adverse outcomes in hypertensive patients with CAD are poorly
      understood. The INternational VErapamil-trandolapril STudy (INVEST) compared
      outcomes in hypertensive patients with CAD that were assigned randomly to either
      a verapamil sustained-release (SR)- or an atenolol-based strategy for blood
      pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added
      agents. During follow-up (61,835 patient-years), BP control and the primary
      outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not
      different between strategies. METHODS: We investigated risk for adverse outcome
      associated with baseline factors, follow-up BP, and drug treatments using Cox
      modeling. RESULTS: Previous heart failure (adjusted hazard ratio [HR] 1.96), as
      well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61),
      renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking
      (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR
      1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up
      systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively)
      and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with
      reduced risk. CONCLUSIONS: In hypertensive patients with CAD, increased risk for
      adverse outcomes was associated with conditions related to the severity of CAD
      and diminished left ventricular function. Lower follow-up BP and addition of
      trandolapril to verapamil SR each were associated with reduced risk.

PMID- 16458135
TI  - B-type natriuretic peptide and the risk of cardiovascular events and death in
      patients with stable angina: results from the AtheroGene study.
AB  - OBJECTIVES: The aim of this study was to assess the predictive value of the
      cardiac hormone B-type natriuretic peptide (BNP) for long-term outcome in a large
      cohort of stable angina patients. BACKGROUND: Recent data suggest a role of BNP
      in stable ischemic heart disease beyond its known value in heart failure and
      acute coronary syndromes. METHODS: In 1,085 patients with coronary artery disease
      (CAD) baseline levels of BNP were prospectively associated with cardiovascular
      (CV) events during a mean follow-up of 2.5 years. RESULTS: BNP concentrations
      were significantly elevated in patients with future CV events (median [25th/75th
      interquartile range] 119.2 [43.6/300.4] pg/ml vs. 36.2 [11.3/94.6] pg/ml; p <
      0.001). Kaplan-Meier survival analysis showed a stepwise decrease in event-free
      survival across quartiles of BNP baseline concentration (p(log rank) < 0.001).
      Patients in the highest quartile revealed a 6.1-fold increased risk (p = 0.001)
      compared to patients in the lowest quartile after adjustment for potential
      confounders. For a cut-off value of 100 pg/ml, an independently increased risk of
      adverse outcome (hazard ratio [HR] 4.4; p < 0.001) could be demonstrated. One
      standard deviation (SD) decrease in ejection fraction implied the most prominent
      increase in risk of future CV events (HR 1.69; p < 0.001) followed by one SD
      increase in BNP (HR 1.53; p < 0.001). The highest prognostic accuracy could be
      demonstrated for BNP (area under the curve 0.671). CONCLUSIONS: The data of this
      large group of CAD patients provide independent evidence that BNP is a strong
      predictor of cardiovascular risk in patients with stable angina independent of
      left ventricular systolic performance and known risk factors.

PMID- 16458136
TI  - Tibolone improves myocardial perfusion in postmenopausal women with ischemic
      heart disease: an open-label exploratory pilot study.
AB  - OBJECTIVES: We sought to determine the effect of tibolone on myocardial perfusion
      in postmenopausal women with ischemic heart disease. BACKGROUND: Tibolone is a
      steroid that relieves climacteric symptoms and prevents osteoporosis. Recent
      studies have suggested a cardioprotective effect of this compound. However, its
      role on myocardial perfusion remains uncertain. METHODS: Single-photon emission
      computed tomography myocardial perfusion imaging was performed in 26
      postmenopausal women. Patients were randomly assigned to tibolone for six months
      (treatment group) or to usual care (control group). All women underwent cardiac
      imaging at baseline and at six months. RESULTS: Mean stress perfusion defect
      (summed stress score) was moderate and did not differ between the two groups (8
      +/- 3 vs. 9 +/- 4; p = NS). Summed difference score also was similar for both
      groups (7 +/- 3 vs. 8 +/- 3; p = NS). The six-month study revealed that summed
      stress and summed difference scores significantly improved in the treatment group
      (to 3 +/- 3 and to 2 +/- 2; p < 0.001) whereas it remained unchanged for control
      patients (to 10 +/- 4 and to 8 +/- 2; p = NS). CONCLUSIONS: In postmenopausal
      women with ischemic heart disease, six months of therapy with tibolone
      significantly improved stress myocardial perfusion and the "amount of ischemia."

PMID- 16458137
TI  - Coronary risk factors and myocardial perfusion in asymptomatic adults: the Multi
      Ethnic Study of Atherosclerosis (MESA).
AB  - OBJECTIVES: The purpose of this study was to determine the cross-sectional
      relation between myocardial perfusion and coronary heart disease (CHD) risk
      factors among adults with no clinical CHD. BACKGROUND: Clinical studies suggest
      that myocardial perfusion is often abnormal in individuals without CHD but with
      risk factors. Epidemiologic study in asymptomatic populations is lacking.
      METHODS: Two hundred twenty-two men and women, ages 45 to 84 years and free of a
      CHD diagnosis, in the University of Minnesota field center of the Multi-Ethnic
      Study of Atherosclerosis (MESA) had myocardial blood flow (MBF) determined using
      cardiac magnetic resonance imaging at rest and during adenosine-induced
      hyperemia. Perfusion reserve (PR) was calculated as the ratio of hyperemic to
      rest MBF. RESULTS: Both resting and hyperemic MBF were lower in men than in
      women, even after considering age and menopause. Hyperemic MBF was also
      significantly lower in subjects who were older, and in those with higher blood
      pressure, higher fasting glucose, and lower low-density lipoprotein cholesterol.
      After adjusting for age, gender, and race, reduced PR was independently
      associated with hypertension, higher diastolic blood pressure, and higher total
      and low-density lipoprotein cholesterol, but was not associated with cigarette
      smoking, obesity, physical activity, or diabetes. Moreover, hyperemic MBF and PR
      were correlated strongly and inversely with estimated 10-year CHD risk based on
      Framingham equations (p for trends: <0.0001). CONCLUSIONS: Coronary
      vasoreactivity is reduced in asymptomatic individuals with a greater coronary
      risk factor burden. Our study results imply that changes in coronary vascular
      reactivity, in response to risk factors, may be detected in adults without
      symptomatic CHD.

PMID- 16458138
TI  - Plasma nitroso compounds are decreased in patients with endothelial dysfunction.
AB  - OBJECTIVES: We investigated whether plasma nitros(yl)ated species (RXNOs) that
      mediate systemic nitric oxide (NO) bioactivity are depleted in individuals with
      cardiovascular risk factors and endothelial dysfunction. BACKGROUND: Endothelium
      derived NO acts not only as a regional messenger but exerts significant systemic
      effects via formation of circulating RXNOs delivering NO to sites of impaired
      production. METHODS: Endothelial function was assessed in 68 patients with one to
      four major cardiovascular risk factors (RF) and 39 healthy control subjects (C)
      by measurement of flow-mediated dilation (FMD) of the brachial artery using high
      resolution ultrasound. In parallel, plasma RXNOs were determined by reductive gas
      phase chemiluminescence. RESULTS: Increasing numbers of risk factors were
      accompanied by a progressive decrease in FMD: 6.5 +/- 0.4% (C); 4.7 +/- 0.5% (one
      RF); 2.8 +/- 0.4% (two RF); 2.2 +/- 0.4% (three RF); and 1.0 +/- 0.3% (four RF).
      Progressively impaired vascular function was associated with a concomitant
      decrease in plasma RXNOs (p < 0.01): 39 +/- 2 nmol/l (C); 30 +/- 2 nmol/l (one
      RF); 24 +/- 3 nmol/l (two RF); 22 +/- 3 nmol/l (three RF); and 15 +/- 2 nmol/l
      (four RF), with univariate correlation between FMD and RXNO (r = 0.41, p <
      0.001). In a multivariate regression model, RXNO was an independent predictor of
      endothelial function. CONCLUSIONS: Endothelial dysfunction in patients with
      cardiovascular risk factors is associated with decreased levels of circulating
      RXNOs. Plasma RXNOs may be diagnostically useful markers of NO bioavailability
      and a surrogate index of endothelial function. Whether the observed decrease in
      concentration reflects impaired NO formation, accelerated decomposition, and/or
      consumption of RXNOs and whether these processes play a causal role in the
      pathophysiology of arteriosclerosis remain to be investigated.

PMID- 16458139
TI  - Nitric oxide metabolites and cardiovascular disease markers, mediators, or both?

PMID- 16458140
TI  - Relationship between renal function and plasma brain natriuretic peptide in
      patients with heart failure.
AB  - OBJECTIVES: This study sought to evaluate the relationship between brain
      natriuretic peptide (BNP), renal function, and the severity of congestive heart
      failure (CHF). BACKGROUND: Both BNP and renal function are prognostic predictors
      in CHF patients. METHODS: We measured the plasma BNP level in the aortic root and
      coronary sinus in 366 consecutive patients with CHF. Estimated glomerular
      filtration rate (eGFR) by the Cockcroft-Gault equation was used as an indicator
      of renal function. RESULTS: By stepwise multivariate analyses, hemodynamic
      parameters such as left ventricular ejection fraction (LVEF) and left ventricular
      end-diastolic pressure (LVEDP) but not eGFR were independent predictors of a
      transcardiac increase (coronary sinus-aortic root) in BNP. Regarding the plasma
      level of BNP in the aortic root, not only LVEF (p < 0.0001) and LVEDP (p <
      0.0001) but also eGFR (p < 0.0001) were independent predictors. Patients were
      divided into two groups, patients with an eGFR > or =60 ml/min (group 1, n = 229)
      and patients with an eGFR <60 ml/min (group 2, n = 137). There was no difference
      in LVEF, LVEDP, or the transcardiac gradient of BNP between the two groups, but
      the plasma level of BNP in the aortic root was approximately two-fold greater in
      group 2 than in the group 1. CONCLUSIONS: These findings suggest that decreased
      clearance from the kidney contributes to the elevated BNP in CHF patients with
      renal dysfunction, especially in patients with an eGFR <60 ml/min.

PMID- 16458141
TI  - An implantable loop recorder study of highly symptomatic vasovagal patients: the
      heart rhythm observed during a spontaneous syncope is identical to the recurrent
      syncope but not correlated with the head-up tilt test or adenosine triphosphate
      test.
AB  - OBJECTIVES: The aim of this study was to analyze the heart rhythm during
      spontaneous vasovagal syncope (VVS) in highly symptomatic patients with
      implantable loop recorders (ILR) and to correlate this rhythm with the heart
      rhythm observed during head-up tilt test (HUT). BACKGROUND: Heart rhythm obtained
      during provocative condition is often used to guide therapy in VVS. To date there
      is no conclusive evidence that the heart rhythm observed during a positive HUT
      can predict heart rhythm during VVS or that the heart rhythm observed during a
      spontaneous syncope will be identical to the recurrent syncope. METHODS: Twenty
      five consecutive VVS patients (age 60.2 +/- 17.1 years; 14 women,) presenting
      with frequent syncopes (6.9 +/- 4.6 episodes/year) and a positive HUT
      (cardioinhibitory in 8 patients) were implanted with an ILR. Seven of them also
      had a positive adenosine triphosphate (ATP) test. RESULTS: Follow-up was 17.0 +/-
      3.6 months. Thirty VVS were observed in 12 patients. Nine episodes showed
      bradycardia of <40 beats/min or asystole; progressive sinus bradycardia preceding
      sinus arrest was the most frequent electrocardiographic finding. Twenty-one
      syncopes occurred without severe bradycardia. The heart rhythm observed during
      the first syncope was identical to the recurrence. No correlation was found
      between slow heart rate at the ILR interrogation and a cardioinhibitory HUT
      response (p = 1.0) or a positive ATP test (p = 1.0). CONCLUSIONS: In highly
      symptomatic patients with VVS, the heart rhythm observed during spontaneous
      syncope does not correlate with the HUT. The heart rhythm during the first
      spontaneous syncope is identical to the recurrent syncope.

PMID- 16458142
TI  - Epidemiology, clinical features, and follow-up of patients with syncope and a
      positive adenosine triphosphate test result.
AB  - OBJECTIVES: We sought to evaluate epidemiology, clinical features, and outcomes
      of patients with syncope and an abnormal response to adenosine triphosphate
      (ATP). BACKGROUND: Syncope remains of unknown origin in almost 30% of the
      patients. Injection of ATP induces in some of these patients, but not in control
      patients, a ventricular pause > or =6 s. METHODS: Patients with syncope of
      unknown origin had an intravenous injection of 20 mg of ATP. All patients had a
      tilt test. RESULTS: Among 214 patients, 19 (8.9%) had a positive ATP test result.
      The proportion of positive test results was higher (p < 0.002) in women (14.3%)
      than in men (2.2%). Ten patients (4.7%) had positive ATP and tilt test results.
      These patients (exclusively women) were older (p < 0.05) at the time of their
      fist syncope than the 67 patients with a negative ATP test result but a positive
      tilt test result. There was a trend for these two test results to be correlated
      (p = 0.07). Side effects were of short duration and benign. The mean duration of
      pauses was longer in women (p = 0.009). During a mean period of 31 +/- 14 months,
      recurrences of syncope were reported in 25% of patients. CONCLUSIONS: The ATP
      test is a safe test with an "abnormal" result in <10% of patients with syncope of
      unknown origin. The profile of these patients is characteristic.

PMID- 16458143
TI  - Increased myocardial fatty acid metabolism in patients with type 1 diabetes
      mellitus.
AB  - OBJECTIVES: The purpose of this study was to determine if myocardial fatty acid
      utilization (MFAU) and myocardial fatty acid oxidation (MFAO) are increased in
      diabetic patients. BACKGROUND: Experimental models of diabetes mellitus
      demonstrate that MFAU and MFAO are increased, and that this dependence on
      myocardial fatty acid metabolism may be detrimental to cardiac function. Whether
      similar metabolic changes occur in humans with diabetes mellitus is unclear.
      METHODS: Eleven healthy non-diabetic control patients (5 women, ages 25 +/- 5
      years) and 11 otherwise healthy patients with type 1 diabetes mellitus (T1DM) (8
      women, ages 36 +/- 10 years, HbA1c 8.4 +/- 1.9%) underwent positron emission
      tomography for the determination of myocardial blood flow (MBF); myocardial
      oxygen consumption (MVO2); myocardial glucose utilization (MGU); and MFAU, MFAO,
      and %MFAO. RESULTS: Plasma lactate, insulin, and MBF levels were similar between
      the two groups. However, plasma glucose (5.71 +/- 0.98 mumol/ml vs. 5.28 +/- 0.65
      mumol/ml, p = 0.04), free fatty acid levels (0.60 +/- 0.24 mumol/ml vs. 0.19 +/-
      0.07 mumol/ml, p < 0.0001), and MVO2 (6.64 +/- 2.21 vs. 4.51 +/- 1.39
      mumol/g/min, p = 0.007) levels were higher in the T1DM subjects. Furthermore,
      compared with control patients, T1DM subjects exhibited higher MFAU (213 +/- 135
      nmol/g/min vs. 57 +/- 28 nmol/g/min, p = 0.0004), MFAO (206 +/- 131 nmol/g/min s.
      50 +/- 26 nmol/g/min, p = 0.0002), and %MFAO (94 +/- 6% vs. 81 +/- 19%,
      respectively, p = 0.04). In contrast, MGU was lower in T1DM subjects than in
      controls (207 +/- 108 nmol/g/min vs. 403 +/- 191 nmol/g/min, p = 0.0008).
      CONCLUSIONS: Humans with diabetes mellitus exhibit increased MFAU and MFAO and
      reduced MGU consistent with observations obtained in experimental models of
      diabetes.

PMID- 16458144
TI  - Prognostic value of pharmacological stress echocardiography in diabetic and
      nondiabetic patients with known or suspected coronary artery disease.
AB  - OBJECTIVES: We sought to compare the prognostic value of pharmacological stress
      echocardiography (SE) in diabetic and nondiabetic patients with known or
      suspected coronary artery disease. BACKGROUND: Although SE is a useful tool for
      risk stratification of patients with diabetes, it has not been established
      whether it retains the same prognostic information in diabetic patients compared
      with nondiabetic patients. METHODS: A total of 5,456 patients (749 diabetics)
      undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were
      prospectively followed up for the occurrence of hard events (death and/or
      nonfatal myocardial infarction). RESULTS: During a median time of 31 months, 411
      deaths and 236 infarctions occurred. There were 132 events in diabetic patients
      and 515 in nondiabetic patients (18% vs. 11%, respectively; p < 0.0001).
      Moreover, 1,607 (29%) patients underwent coronary revascularization and were
      censored. Ischemia at SE, resting wall motion score index, and age were
      independent predictors of death and hard events in both diabetic and nondiabetic
      patients. Compared with a normal test, ischemia and scar test patterns were
      associated to significantly lower age-corrected five-year hard event-free
      survival in diabetic as well as nondiabetic patients. However, a normal test was
      associated with a greater than two-fold annual event rate in diabetic patients as
      compared with nondiabetics who were either younger (2.6% vs. 1.0%) or older (5.5%
      vs. 2.2%) than 65 years of age. CONCLUSIONS: Stress echocardiography is equally
      effective in risk stratifying diabetic and nondiabetic patients independently of
      age. However, the normal test result predicts a less favorable outcome in
      diabetic than in nondiabetic patients.

PMID- 16458145
TI  - Association of subclinical right ventricular dysfunction with obesity.
AB  - OBJECTIVES: The purpose of this research was to identify the determinants of
      right ventricular (RV) dysfunction in overweight and obese subjects. BACKGROUND:
      Right ventricular dysfunction in obese subjects is usually ascribed to comorbid
      diseases, especially obstructive sleep apnea. We used tissue Doppler imaging to
      identify the determinants of RV dysfunction in overweight and obese subjects.
      METHODS: Standard and tissue Doppler echocardiography was performed in 112
      overweight (body mass index [BMI] 25 to 29.9 kg/m2) or obese (BMI >30 kg/m2)
      subjects and 36 referents (BMI <25 kg/m2), including 22 with obstructive sleep
      apnea but no obesity. Tissue Doppler was used to measure RV systolic (s(m)) and
      diastolic (e(m)) velocities and strain indexes. RESULTS: Obese subjects with BMI
      >35 kg/m2 had reduced RV function compared with referent subjects, evidenced by
      reduced s(m) (6.5 +/- 2.4 cm/s vs. 10.2 +/- 1.5 cm/s, p < 0.001), peak strain (
      21 +/- 4% vs. -28 +/- 4%, p < 0.001), peak strain rate (-1.4 +/- 0.4 s(-1) vs. 
      2.0 +/- 0.5 s(-1), p < 0.001), and e(m) (-6.8 +/- 2.4 cm/s vs. -10.3 +/- 2.5
      cm/s, p < 0.001), irrespective of the presence of sleep apnea. Similar but lesser
      degrees of reduced systolic function (p < 0.05) were present in overweight (BMI
      25 to 29.9 kg/m2) and mildly obese (BMI 30 to 35 kg/m2) groups. Differences in RV
      e(m), s(m), and strain indexes were demonstrated between the severely versus
      overweight and mildly obese groups (p < 0.05). Body mass index remained
      independently related to RV changes after adjusting for age, log insulin, and
      mean arterial pressures. In obese patients, these changes were associated with
      reduced exercise capacity but not the duration of obesity and presence of sleep
      apnea or its severity. CONCLUSIONS: Increasing BMI is associated with increasing
      severity of RV dysfunction in overweight and obese subjects without overt heart
      disease, independent of sleep apnea.

PMID- 16458146
TI  - The growing problem of obesity and the heart: the plot "thickens".

PMID- 16458147
TI  - Assessment of renal flow and flow reserve in humans.
AB  - OBJECTIVES: The purpose of this work was to establish the normal range of maximal
      renal hyperemic response in humans and to identify the ideal renal vasodilatory
      stimuli. BACKGROUND: Stenotic renovascular atherosclerosis is increasingly
      treated by percutaneous transluminal renal intervention but with an unpredictable
      outcome. This may be due to hemodynamically non-significant stenosis or the
      presence of irreversible damage to the glomerular circulation. We propose that
      the renovascular hyperemic response may help identify appropriate patients.
      METHODS: In 28 normotensive patients, quantitative angiographic measurements of
      the renal artery were obtained, and renal artery pressure and flow velocity were
      continuously recorded after various hyperemic agents. RESULTS: In a first group
      of 11 patients, a significant increase in renal artery average peak velocity
      (APV) was observed after intrarenal (IR) bolus injection of 600 microg isosorbide
      dinitrate (41 +/- 19%), 30 mg papaverine (50 +/- 34%), 50 microg dopamine (94 +/-
      54%), 0.8 microg x kg(-1) fenoldopam (80 +/- 25%), and during IR infusion of 1
      microg x kg(-1) x min(-1) fenoldopam (86 +/- 28%). A second group of 17 patients
      received intravenous infusion of dopamine (3, 5, 10, 20, 30, and 40 microg x kg(
      1) x min(-1)). The 3 and 5 microg x kg(-1) x min(-1) of dopamine modestly reduced
      renal resistance index (RI) (-13 +/- 15% and -25 +/- 20%, respectively). At
      higher dosages, no further decline in RI was observed. No significant change in
      vessel diameter was observed before and after the administration of the
      pharmacological stimuli suggesting that changes in APV corresponded with changes
      in absolute renal blood flow. CONCLUSIONS: The normal renal flow reserve averages
      approximately 2 in humans with normal renal function. An IR bolus injection of 50
      microg x kg(-1) of dopamine is the most convenient means to elicit maximal renal
      hyperemia.

PMID- 16458149
TI  - Chronic recurrent myocardial ischemic injury is significantly attenuated by pre
      emptive adeno-associated virus heme oxygenase-1 gene delivery.
AB  - OBJECTIVES: We assessed the hypothesis that overexpression of the antioxidant
      enzyme heme oxygenase (HO)-1 may protect against chronic recurrent
      ischemia/reperfusion injury. BACKGROUND: Multiple and recurring episodes of
      myocardial ischemia can result in significant myocardial damage, including
      myocyte death, fibrosis, and wall thinning, leading to impaired ventricular
      function and cardiac failure. METHODS: In this study we used a closed-chest
      rodent model of chronic recurring myocardial ischemia and reperfusion to
      investigate the efficacy of pre-emptive gene therapy in overexpressing the
      antioxidant enzyme HO-1, using adeno-associated virus (AAV)-2 as the delivery
      vector. RESULTS: We show that constitutive overexpression of HO-1 can prevent
      myocardial wall thinning, inflammation, fibrosis, and deterioration of cardiac
      function (as measured by echocardiography, histology, and immunohistochemistry)
      induced by repeated transient myocardial ischemia and reperfusion injury. With HO
      1 therapy, there was a significant reduction in apoptosis as determined by levels
      of markers of survival proteins and terminal deoxynucleotidyltransferase dUTP
      nick end-labeling staining. This prevention of tissue damage was also associated
      with reduction in superoxide generation. CONCLUSIONS: Taken together we provide
      the first evidence of the therapeutic efficacy of pre-emptive AAV-HO-1 delivery
      for prevention against multiple ischemic injury. This approach protects myocytes
      by simultaneously activating protective response and inhibiting pathological left
      ventricular remodeling and, therefore, may be a useful cardio-protective strategy
      for patients with coronary artery disease at a high risk for recurrent myocardial
      ischemia.

PMID- 16458148
TI  - Macrophage colony-stimulating factor treatment after myocardial infarction
      attenuates left ventricular dysfunction by accelerating infarct repair.
AB  - OBJECTIVES: We aimed to determine the effects of macrophage colony-stimulating
      factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) treatment on
      both the repair process and ventricular function after myocardial infarction
      (MI). BACKGROUND: The M-CSF and G-CSF have multiple potential effects on cells
      involved in wound repair. METHODS: Myocardial infarction was induced by 45- or 90
      min coronary occlusion and reperfusion in rats with or without subsequent
      injection of M-CSF (10(6) IU/kg/day) or G-CSF (50 microg/kg/day) for five days.
      We examined histology and messenger ribonucleic acid (mRNA), and assessed left
      ventricular function in situ using a conductance catheter. RESULTS: Five days
      after MI, M-CSF increased the number of ED-1-positive cells, mRNA levels of
      transforming growth factor-beta-1, collagen I and III, and collagen fibers within
      the infarct. Fourteen days after MI, induced by 45-min ischemia, left ventricular
      end-systolic elastance (Ees) was reduced (1,191 +/- 87 mm Hg/ml vs. 1,812 +/- 150
      mm Hg/ml) and both isovolumic relaxation time constant (tau) (11.9 +/- 0.9 ms vs.
      8.5 +/- 0.4 ms) and left ventricular end-diastolic volume (LVEDV) (0.225 +/-
      0.014 ml vs. 0.172 +/- 0.011 ml) increased versus sham-operated rats. These
      alterations after MI were attenuated by M-CSF (Ees = 1,650 +/- 146, tau = 9.7 +/-
      0.7, LVEDV = 0.199 +/- 0.012) but not by G-CSF. This beneficial effect of M-CSF
      on Ees was also detected in hearts with MI induced by 90-min ischemia.
      Furthermore, M-CSF increased collagen content within infarcts and reduced the
      proportion of thin collagen fibers 14 days after MI. The Ees significantly
      correlated with infarct collagen content. Nevertheless, neither M-CSF nor G-CSF
      modified infarct size. CONCLUSIONS: The M-CSF treatment attenuates deterioration
      of left ventricular function after MI by accelerating infarct repair.

PMID- 16458150
TI  - Chronic atrial dilation, electrical remodeling, and atrial fibrillation in the
      goat.
AB  - OBJECTIVES: This study was designed to investigate the mutual effects of chronic
      atrial dilation and electrical remodeling on the characteristics of atrial
      fibrillation (AF). BACKGROUND: Both electrical remodeling and atrial dilation
      promote the inducibility and perpetuation of AF. METHODS: In seven goats AF was
      induced during 48 h by burst pacing, both at baseline and after four weeks of
      slow idioventricular rhythm (total AV block). Atrial size and refractory period
      (AERP) were monitored together with the duration and cycle length of AF paroxysms
      (AFCL). After four weeks of total atrioventricular (AV) block, the conduction in
      both atria was mapped during AF. Six non-instrumented goats served as controls.
      RESULTS: At baseline, AF-induced electrical remodeling shortened AERP and AFCL to
      the same extent (from 185 +/- 9 ms to 149 +/- 14 ms [p < 0.05] and from 154 +/-
      11 ms to 121 +/- 5 ms [p < 0.05], respectively). After four weeks of AV block the
      right atrial diameter had increased by 13.2 +/- 3.0% (p < 0.01). Surprisingly, in
      dilated atria electrical remodeling still shortened the AERP (from 165 +/- 9 ms
      to 132 +/- 15 ms [p < 0.05]) but failed to shorten the AFCL (140 +/- 19 ms vs.
      139 +/- 11 ms [p = 0.98]). Mapping revealed a higher incidence of intra-atrial
      conduction delays during AF. Histologic analysis showed no atrial fibrosis but
      did reveal a positive correlation between the size of atrial myocytes and the
      incidence of intra-atrial conduction block (r = 0.60, p = 0.03). CONCLUSIONS: In
      a goat model of chronic atrial dilation, AF-induced electrical remodeling was
      unchanged. However, AFCL no longer shortened during electrical remodeling. Thus,
      in dilated atria a wider excitable gap exists during AF, probably caused by intra
      atrial conduction defects and a higher contribution of anatomically defined re
      entrant circuits.

PMID- 16458151
TI  - A risk score to predict in-hospital mortality for percutaneous coronary
      interventions.
AB  - OBJECTIVES: Our purpose was to develop a risk score to predict in-hospital
      mortality for percutaneous coronary intervention (PCI) using a statewide
      population-based PCI registry. BACKGROUND: Risk scores predicting adverse
      outcomes after PCI have been developed from a single or a small group of
      hospitals, and their abilities to be generalized to other patient populations
      might be affected. METHODS: A logistic regression model was developed to predict
      in-hospital mortality for PCI using data from 46,090 procedures performed in 41
      hospitals in the New York State Percutaneous Coronary Intervention Reporting
      System in 2002. A risk score was derived from this model and was validated using
      2003 data from New York. RESULTS: The risk score included nine significant risk
      factors (age, gender, hemodynamic state, ejection fraction, pre-procedural
      myocardial infarction, peripheral arterial disease, congestive heart disease,
      renal failure, and left main disease) that were consistent with other reports.
      The point values for risk factors range from 1 to 9, and the total risk score
      ranges from 0 to 40. The observed and recalibrated predicted risks in 2003 were
      highly correlated for all PCI patients as well as for those in the higher-risk
      subgroup who suffered myocardial infarctions within 24 h before the procedure.
      The total risk score for mortality is strongly associated with complication rates
      and length of stay in the 2003 PCI data. CONCLUSIONS: The risk score accurately
      predicted in-hospital death for PCI procedures using future New York data. Its
      performance in other patient populations needs to be further studied.

PMID- 16458152
TI  - Risk stratification of in-hospital mortality for coronary artery bypass graft
      surgery.
AB  - OBJECTIVES: The purpose of this research was to develop a risk index for in
      hospital mortality for coronary artery bypass graft (CABG) surgery. BACKGROUND:
      Risk indexes for CABG surgery are used to assess patients' operative risk as well
      as to profile hospitals and surgeons. None has been developed using data from a
      population-based region in the U.S. for many years. METHODS: Data from New York's
      Cardiac Surgery Reporting System in 2002 were used to develop a statistical model
      that predicts mortality and to create a risk index based on a relatively small
      number of patient risk factors. The fit of the index was tested by applying it to
      another year (2003) of New York data and testing the correspondence of expected
      and observed mortality rates for each risk score in the index. RESULTS: The risk
      index contains a total of 10 risk factors (age, female gender, hemodynamic state,
      ejection fraction, pre-procedural myocardial infarction, chronic obstructive
      pulmonary disease, calcified ascending aorta, peripheral arterial disease, renal
      failure, and previous open heart operations). The score possible for each
      variable ranges from 0 to 5, and total risk scores possible range from 0 to 34.
      The highest score observed for any patient was 22, and 93% of the patients had
      scores of 8 or lower. When the risk index was applied to another year of New York
      data with a considerably lower mortality rate, the C-statistic was 0.782.
      CONCLUSIONS: The risk index appears to be a valuable tool for predicting patient
      risk when applied to another year of New York data. It should now be tested
      against other risk indexes in a variety of geographical regions.

PMID- 16458153
TI  - Evaluating the risk of coronary surgery and percutaneous coronary intervention.

PMID- 16458154
TI  - Accuracy of 64-slice computed tomography to classify and quantify plaque volumes
      in the proximal coronary system: a comparative study using intravascular
      ultrasound.
AB  - OBJECTIVES: We evaluated the accuracy of a new 64-slice computed tomography (CT)
      scanner, compared with intravascular ultrasound, to visualize atherosclerosis in
      the proximal coronary system. BACKGROUND: Noninvasive determination of plaque
      composition and plaque burden may be important to improve risk stratification.
      METHODS: In 20 patients, a 64-slice CT scan (Sensation 64, Siemens Medical
      Solutions, Forchheim, Germany) and an intravascular ultrasound investigation of
      vessels without stenosis >50% was performed. Diagnostic image quality with 64
      slice CT was obtained in 36 vessels in 19 patients. RESULTS: In these vessels,
      which were divided in 3-mm sections, 64-slice CT enabled a correct detection of
      plaque in 54 of 65 (83%) sections containing noncalcified plaques, 50 of 53 (94%)
      sections containing mixed plaques, and 41 of 43 (95%) sections containing
      calcified plaques. In 192 of 204 (94%) sections, atherosclerotic lesions were
      excluded correctly. In addition, 64-slice CT enabled the visualization of 7 of 10
      (70%) sections revealing a lipid pool and could identify a spotty calcification
      pattern in 27 of 30 (90%) sections. The correlation coefficient to determine
      plaque volumes per vessel was r2 = 0.69 (p < 0.001) with an underestimation of
      mixed and noncalcified plaque volumes (p < 0.03) and a trend to overestimate
      calcified plaque volumes by 64-slice CT. The interobserver variability to
      determine plaque volumes was 37%. Interobserver agreement to identify
      atherosclerotic sections was good (Cohen's kappa coefficient = 0.75).
      CONCLUSIONS: We conclude that 64-slice CT reveals encouraging results to
      noninvasively detect different types of coronary plaques located in the proximal
      coronary system. The ability to determine plaque burden currently is hampered by
      mainly an insufficient reproducibility.

PMID- 16458155
TI  - The promise of quantitative computed tomography coronary angiography and
      noninvasive segmental coronary plaque quantification: pushing the "edge".

PMID- 16458156
TI  - President's page: Collaborative culture key to our success.

PMID- 16458157
TI  - Maternal homocysteine and congenital heart defects.

PMID- 16458158
TI  - Relationship between patient's risk profile and benefits in mortality from
      adjunctive abciximab to mechanical revascularization for ST-segment elevation
      myocardial infarction: a meta-regression analysis of randomized trials.

PMID- 16458159
TI  - Integrated backscatter in Becker muscular dystrophy patients with functionally
      normal heart: myocardial ultrasound tissue characterization study.

PMID- 16458160
TI  - Link between arterial inflammation and circadian rhythm: the oversight aspect in
      the year 2004.

PMID- 16458162
TI  - Viruses and other environmental factors as possible sources of phenotypic
      heterogeneity in familial dilated cardiomyopathy.

PMID- 16458163
TI  - Cardiovascular manifestations of carbon monoxide poisoning.

PMID- 16458166
TI  - Ischemic heart disease in women.
AB  - This supplement is intended to provide a specialized forum to overview new
      information on the pathophysiology, diagnosis, and outcomes of women with
      suspected ischemic heart disease (IHD). Led by Women's Ischemic Syndrome
      Evaluation (WISE) study investigators and other experts, the scientific summaries
      contained in this supplement will permit sharing of current knowledge about this
      important clinical problem. Improved understanding in these areas will advance
      the prevention and treatment of IHD in women. These comments by the investigators
      and experts, as well as those from a recent National Heart, Lung, and Blood
      Institute consensus conference, should also provide direction for future studies
      in this critical area.

PMID- 16458168
TI  - Some thoughts on the vasculopathy of women with ischemic heart disease.
AB  - Considerable experimental and clinical data indicate that sex has an important
      influence on cardiovascular physiology and pathology. This report integrates
      selected literature with new data from the Women's Ischemia Syndrome Evaluation
      (WISE) on vascular findings in women with ischemic heart disease (IHD) and how
      these findings differ from those in men. A number of common vascular disease
      related conditions are either unique to (e.g., hypertensive disorders of
      pregnancy, gestational diabetes, peripartum dissection, polycystic ovarian
      syndrome, etc.) or more frequent (e.g., migraine, coronary spasm, lupus,
      vasculitis, Raynaud's phenomenon, etc.) in women than men. Post-menopausal women
      more frequently have many traditional vascular disease risk conditions (e.g.,
      hypertension, diabetes, obesity, inactivity, and so on), and these conditions
      cluster more frequently in them than men. Considerable evidence supports the
      notion that, with these requisite conditions, women develop a more severe or
      somewhat different form of vascular disease than men. Structurally, women's
      coronary vessels are smaller in size and appear to contain more diffuse
      atherosclerosis, their aortas are stiffer (fibrosis, remodeling, and so on), and
      their microvessels appear to be more frequently dysfunctional compared with men.
      Functionally, women's vessels frequently show impaired vasodilator responses.
      Limitations of existing data and higher risks in women with acute myocardial
      infarction, need for revascularization, or heart failure create uncertainty about
      management. A better understanding of these findings should provide direction for
      new algorithms to improve management of the vasculopathy underlying IHD in women.

PMID- 16458167
TI  - Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE)
      Study: Part II: gender differences in presentation, diagnosis, and outcome with
      regard to gender-based pathophysiology of atherosclerosis and macrovascular and
      microvascular coronary disease.
AB  - Coronary heart disease is the leading cause of death and disability in the U.S.,
      but recent advances have not led to declines in case fatality rates for women.
      The current review highlights gender-specific issues in ischemic heart disease
      (IHD) presentation, evaluation, and outcomes with a special focus on the results
      derived from the National Institutes of Health-National Heart, Lung, and Blood
      Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In the
      second part of this review, we will assess new evidence on gender-based
      differences in vascular wall or metabolic alterations, atherosclerotic plaque
      deposition, and functional expression on worsening outcomes of women.
      Additionally, innovative cardiovascular imaging techniques will be discussed.
      Finally, we identify critical areas of further inquiry needed to advance this new
      gender-specific IHD understanding into improved outcomes for women.

PMID- 16458169
TI  - The value of estimated functional capacity in estimating outcome: results from
      the NHBLI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study.
AB  - OBJECTIVES: Our objective was to determine the prognostic value of estimated
      metabolic equivalents (METs) based on self-reported functional capacity by the
      Duke Activity Status Index (DASI) in symptomatic women. BACKGROUND: Functional
      capacity is an important component affecting the predictive value of exercise
      testing, yet current guidelines offer limited assistance regarding identification
      of functional impairment and choice of pharmacologic stress testing. METHODS: A
      total of 914 women underwent clinically indicated coronary angiography and
      completed the 12-item DASI questionnaire; a subgroup of 251 women also underwent
      exercise testing. Cox proportional hazards modeling was used to estimate five
      year death or myocardial infarction by DASI scores. In a secondary analysis,
      additional events included unstable angina, heart failure, or stroke at five
      years. RESULTS: Average DASI-estimated functional capacity was 5.7 +/- 4.2 METs
      and, for exercising women, 6.0 +/- 2.6 METs. In the 914 women, event-free
      survival ranged from 83% to 95% in subgroups with < or =4.7 to >9.9 METs (p =
      0.009); 67% of the events occurred in women scoring < or =4.7 METs (p = 0.003).
      Event rates were similar by exercise and DASI MET values. In women with DASI
      estimated METs < or =4.7 (n = 75), ischemia occurred less (39% vs. 64%, p <
      0.0001), and exercise testing results were more often indeterminate (<85%
      predicted maximum heart rate = 37% vs. 6%, p = 0.001) as compared to women
      achieving >4.7 METs. CONCLUSIONS: Among women with suspected myocardial ischemia,
      functional impairment estimated by the DASI correlates with indeterminate
      exercise test results and is associated with an adverse prognosis. Use of the
      DASI before exercise testing can risk stratify symptomatic women and may improve
      the identification of higher-risk, functionally impaired subjects that would
      benefit from pharmacologic stress imaging and targeted risk management.

PMID- 16458170
TI  - Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE)
      Study: Part I: gender differences in traditional and novel risk factors, symptom
      evaluation, and gender-optimized diagnostic strategies.
AB  - Despite a dramatic decline in mortality over the past three decades, coronary
      heart disease is the leading cause of death and disability in the U.S.
      Importantly, recent advances in the field of cardiovascular medicine have not led
      to significant declines in case fatality rates for women when compared to the
      dramatic declines realized for men. The current review highlights gender-specific
      issues in ischemic heart disease presentation, evaluation, and outcomes with a
      special focus on the results published from the National Institutes of Health
      National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome
      Evaluation (WISE) study. We will present recent evidence on traditional and novel
      risk markers (e.g., high sensitivity C-reactive protein) as well as gender
      specific differences in symptoms and diagnostic approaches. An overview of
      currently available diagnostic test evidence (including exercise
      electrocardiography and stress echocardiography and single-photon emission
      computed tomographic imaging) in symptomatic women will be presented as well as
      data using innovative imaging techniques such as magnetic resonance
      subendocardial perfusion, and spectroscopic imaging will also be discussed.

PMID- 16458171
TI  - Impaired coronary vascular reactivity and functional capacity in women: results
      from the NHLBI Women's Ischemia Syndrome Evaluation (WISE) Study.
AB  - OBJECTIVES: We investigated the relationship between coronary vascular reactivity
      and functional capacity as assessed from the Duke Activity Status Index (DASI) in
      a cohort of women evaluated for suspected ischemia. BACKGROUND: Reduced
      functional capacity and impaired vascular reactivity are associated with poor
      prognosis, but an association between vascular reactivity and functional capacity
      is unknown. METHODS: A total of 190 women enrolled in the National Heart, Lung,
      and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE)
      study had baseline clinical assessment and coronary artery flow velocity response
      to adenosine (CFVR(ado)). We compared these results with self-reported DASI
      metabolic equivalents (METs). RESULTS: Mean age was 55 +/- 11 years (range 21 to
      83 years), and only 18% had coronary stenosis > or =50%. Women with a CFVR(ado)
      <2.5 (n = 98) had mean DASI of 15.1 +/- 13.6, compared to women (n = 92) with
      CFVR(ado) > or =2.5, whose mean DASI was 21.0 +/- 15.2 (p = 0.004). This
      relationship was maintained after adjusting for age and presence of coronary
      artery disease. CFVR(ado) of > or =2.5 was associated with a DASI of >20 (odds
      ratio 3.03, 95% confidence interval 1.56 to 5.90, p = 0.001). CONCLUSIONS: Women
      with reduced CFVR(ado) were significantly more likely to have reduced functional
      capacity. Impairment in coronary vascular function and reduced levels of activity
      may both play a role in the poorer prognosis observed in the WISE study women;
      however, the relationship between the two is still unclear.

PMID- 16458172
TI  - Hypertension, menopause, and coronary artery disease risk in the Women's Ischemia
      Syndrome Evaluation (WISE) Study.
AB  - OBJECTIVES: We evaluated whether the relationship between hypertension, other
      cardiac risk factors, and coronary artery disease (CAD) is modulated by
      menopausal status and/or age. BACKGROUND: The relative contribution of age versus
      menopausal status in the development of CAD in women remains unclear. METHODS: We
      compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse
      pressure (PP), and traditional cardiac risk factors for CAD in premenopausal (n =
      123) and postmenopausal (n = 482) women undergoing coronary angiography for
      suspected ischemia. To assess the relative contribution of age versus menopausal
      status, we fit a hypertension-menopausal status interaction term and adjusted for
      age. RESULTS: There were similar relationships with regard to traditional
      coronary risk factors and angiographic CAD in premenopausal versus postmenopausal
      women, with few exceptions. Twenty percent of premenopausal women had
      angiographic CAD versus 31% of postmenopausal women (p = 0.02). Premenopausal
      women had lower mean (standard deviation) SBP (132 [25] vs. 139 [20] mm Hg; p <
      0.0001) and lower PP (54 [18] vs. 62 [18] mm Hg; p < 0.0001) compared to
      postmenopausal women; however, multivariable analyses revealed that SBP was a
      risk factor for CAD in premenopausal (p = 0.002) but not postmenopausal women (p
      = 0.13), and regression slopes were significantly different (p = 0.04). This
      interaction effect remained after age adjustment, suggesting independent risk
      contribution from both age and menopausal status. A similar slope difference was
      observed for PP (p = 0.03) but not for DBP. CONCLUSIONS: Among women undergoing
      angiography for suspected ischemia, elevated SBP and PP are potent risk factors
      in premenopausal women. The results suggest that identification of hypertension
      in premenopausal women dictates additional CAD risk factor assessment and
      management.

PMID- 16458173
TI  - Women and cardiovascular heart disease: clinical implications from the Women's
      Ischemia Syndrome Evaluation (WISE) Study. Are we smarter?
AB  - Review of the trend in cardiovascular disease mortality for males and females
      clearly demonstrated that whereas the trend shows a decline in males this decline
      is not observed in females. Multiple important reports emerged from the initial
      phases of the Women's Ischemic Syndrome Evaluation (WISE) study that may have
      significant clinical implications for our approach to cardiovascular disease in
      women. The data derived from the WISE study certainly provided important
      information to our understanding of the approach to women with cardiovascular
      disease. The clinical presentation may be different, and a gender-oriented
      questionnaire may enhance our diagnosis. In a multivariable model, low hemoglobin
      was associated with significantly higher risk of adverse outcomes. The risk
      factor assessment and the risk factor profiles in women that are associated with
      coronary artery disease may be different. Based on the studies from the WISE
      study, metabolic syndrome is a leading and a major risk factor in women.
      Moreover, the data further support the concept that the mechanism of ischemia in
      women may be localized in the microvascular coronary arteries. Therefore, the
      diagnoses of coronary microvascular dysfunction or endothelial dysfunction should
      be considered in women with chest pain who do not have obstructive coronary
      artery disease. It may be advantageous to add such diagnostic tests when the
      conventional tests are nondiagnostic. A revised clinical approach to
      cardiovascular disease in women may be designed and tested based on these
      findings.

PMID- 16458174
TI  - Women, ischemic heart disease, revascularization, and the gender gap: what are we
      missing?
AB  - During the past three decades, numerous reports from single-center databases,
      multicenter registries, and a few randomized trials in patients with ischemic
      heart disease (IHD) undergoing revascularization with both coronary artery bypass
      grafting and percutaneous coronary intervention have noted remarkably consistent
      gender differences in clinical, angiographic, and procedural factors and an
      increased morbidity and mortality in women. Explanations such as alternative
      markers of atherosclerosis and novel risk factors in women, gender-specific
      measures of left ventricular function, and the relationship between disorders
      more common in women with IHD and adverse cardiovascular outcomes are beginning
      to unfold.

PMID- 16458175
TI  - Women and ischemic heart disease: pathophysiologic implications from the Women's
      Ischemia Syndrome Evaluation (WISE) Study and future research steps.
AB  - The current review highlights gender-specific issues in ischemic heart disease
      (IHD) presentation, evaluation, and outcomes with a special focus on the results
      derived from the National Institutes of Health-National Heart, Lung, and Blood
      Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. New
      evidence on gender-based differences in vascular wall, atherosclerotic plaque
      deposition, pathophysiology, and innovative cardiovascular imaging techniques are
      reviewed. Critical areas of further inquiry needed to advance new gender-specific
      IHD understanding are detailed.

PMID- 16458178
TI  - Cancer screening in older adults in an era of genomics and longevity.
AB  - OBJECTIVES: To provide an overview of cancer genomics and cancer screening in
      older adults with a focus on breast, prostate, and colon cancers. DATA SOURCES:
      Journal articles, research articles, and web sites. CONCLUSION: Cancer screening
      in older populations is often in the context of one or more co-morbid conditions,
      cancer survivorship, genomic information, and competing health priorities. The
      field of cancer screening has outgrown the tools available to enable health care
      providers and older adults to make informed cancer screening decisions. Research
      is needed to develop clinical screening tools that integrate age, cancer risk,
      life expectancy, and comorbidity. IMPLICATIONS FOR NURSING PRACTICE: Health care
      providers are faced with opportunities and challenges in the prevention and early
      detection of cancer in older Americans.

PMID- 16458177
TI  - Geriatric neutrophils: implications for older adults.
AB  - OBJECTIVES: To review the intersection of immunosenescence and neutropenia,
      focusing on innate immunity, and implications for research and practice for
      neutropenic older adults with cancer. DATA SOURCES: Research studies, journal
      articles, and web sites. CONCLUSION: Immunosenescence, age-related changes within
      the immune system renders older adults more vulnerable to infection. This
      vulnerability is magnified by cancer and its treatment. Unfortunately, there has
      been little consideration of immunosenescence as it relates to supportive care
      for this population. IMPLICATIONS FOR NURSING PRACTICE: Studies detailing the
      impact of immunosenescence on neutropenia and outcomes for neutropenic older
      adults are necessary to advance clinical research and practice.

PMID- 16458179
TI  - Symptom correlates in the gero-oncology population.
AB  - OBJECTIVES: To review recently published studies that describe the presence of
      selected cancer-related symptoms and relationships between them in the gero
      oncology population. DATA SOURCES: Research studies, review articles, and
      government documents. CONCLUSION: Cancer-related symptoms have been studied for
      over two decades, yet little is known about the functional effects of age on the
      disease experience. IMPLICATIONS FOR NURSING PRACTICE: Nurses are encouraged to
      consider symptoms related to other chronic illnesses that contribute to an older
      person's daily living when planning oncology nursing care.

PMID- 16458180
TI  - The trajectory of biomarkers in symptom management for older adults with cancer.
AB  - OBJECTIVES: To provide an overview of the trajectory of select biomarkers and
      their potential usefulness in symptom management in the older individual with
      cancer. DATA SOURCES: Empirical data and literature review. CONCLUSION:
      Biomarkers offer significant opportunities to understand the biological impact of
      cancer and its treatment on older adults whose response is likely different from
      their younger counterparts. Large well-designed multi-site clinical trials with
      adequate numbers and power are necessary to create evidenced-based practice
      changes. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to understand the science
      and implications of biomarkers to develop interventions in response to the
      mechanisms of symptoms experienced by older adults with cancer.

PMID- 16458181
TI  - The effects of neuromuscular alterations in elders with cancer.
AB  - OBJECTIVES: To review the effects of normal aging on declines in function of
      peripheral nerves and muscles and the additive effects of chemotherapy and
      comorbidity in elders undergoing cancer treatment. DATA SOURCES: Research studies
      and published articles. CONCLUSION: Chemotherapy negatively affects physical
      functioning and recovery in elders with cancer through neurotoxicity and
      myotoxicity. Intact sensory nerves and muscles are crucial in maintaining
      physical function and independence for elders. IMPLICATIONS FOR NURSING PRACTICE:
      While older patients with cancer may benefit from chemotherapy, clinical
      practices to minimize toxicities, provide monitoring for functional decline, and
      intervene to maintain function are needed.

PMID- 16458182
TI  - Family care for the older person with cancer.
AB  - OBJECTIVES: To describe the needs of family members of older persons undergoing
      cancer treatment and to examine the interventions designed to alleviate caregiver
      distress. DATA SOURCES: Research studies and published articles. CONCLUSION:
      Interventions to reduce distress for caregivers of older persons with cancer have
      the potential to lower patients' hospital re-admissions and interruptions in
      cancer treatment and to improve patients' and caregivers emotional health.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology practitioners must consider the needs
      of family caregivers when planning and implementing interventions to improve or
      maintain caregiver health.

PMID- 16458183
TI  - Cancer care in nursing homes.
AB  - OBJECTIVES: To review the available scientific literature on cancer care in
      nursing homes and recommendations for clinical practice and further research are
      offered. DATA SOURCES: Research studies and review articles. CONCLUSION:
      Overlooked issues for older adults with cancer in nursing homes include
      screening, treatment, and symptom management. Cancer care and survivorship in
      nursing homes receives little direct attention. IMPLICATIONS FOR NURSING
      PRACTICE: Oncology nurses can improve cancer care and survivorship in nursing
      homes by considering nursing homes as a practice venue.

PMID- 16458184
TI  - Dispelling myths about palliative care and older adults.
AB  - OBJECTIVES: To explore the myths about palliative care and older adults with
      cancer. DATA SOURCES: Research literature and review articles. CONCLUSION:
      Several myths about older adults exist: older adults are the same as younger
      adults, older adults are all the same, and optimizing function and quality of
      life are not important outcomes. Little research has focused on older adults
      receiving palliative care and their families. IMPLICATIONS FOR NURSING PRACTICE:
      The Oncology Nursing Society and Geriatric Oncology Consortium published the
      Joint Position Statement on Cancer Care in Older Adults acknowledging the unique
      needs of older adults with cancer. Application of this statement may be helpful
      in guiding inquiry and practice in the care for older adults receiving palliative
      care.

PMID- 16458185
TI  - Commentary on "Faster plasma vitamin E disappearance in smokers is normalized by
      vitamin C supplementation".

PMID- 16458186
TI  - Redox cycling of iron by Abeta42.
AB  - The amyloid cascade hypothesis and oxidative damage have been inextricably linked
      in the neurodegeneration that is characteristic of Alzheimer's disease. We have
      investigated this link and sought to suggest a mechanism whereby the
      precipitation of Abeta42 might contribute to the redox cycling of iron and hence
      the generation of reactive oxygen species via Fenton-like chemistry. We have
      shown that the critical step in the auto-oxidation of Fe(II) under the near
      physiological conditions of our study involved the generation of H2O2 via O2.-
      and that Abeta42 influenced Fenton chemistry through aggregation state-specific
      binding of both Fe(II) and Fe(III). The net result of these interactions was the
      delayed precipitation of kinetically redox-inactive Fe(OH)3(s) such that
      Fe(II)/Fe(III) were cycled in redox-active forms over a substantially longer time
      period than if peptide had been absent from preparations. The addition of
      physiologically significant concentrations of either Cu(II) or Zn(II) reduced the
      role played by Abeta42 in the Fe(II)/Fe(III) redox cycle whereas a
      pathophysiologically significant concentration of Al(III) potentiated the redox
      cycle in favour of Fe(II) whether or not Cu(II) or Zn(II) was additionally
      present. The results support the notion that oxidative damage in the immediate
      vicinity of, for example, senile plaques, may be the result of Fenton chemistry
      catalysed by the codeposition of Abeta42 with metals such as Fe(II)/Fe(III) and
      Al(III).

PMID- 16458187
TI  - Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and
      catechins.
AB  - Tea phenolic acids and catechins containing gallic acid moieties are most
      abundant in green tea, and various medical benefits have been proposed from their
      consumption. In the following, the cytotoxicities of these major tea phenolics
      toward isolated rat hepatocytes have been ranked and the mechanisms of
      cytotoxicity evaluated. The order of cytotoxic effectiveness found was
      epigallocatechin-3-gallate>propyl gallate>epicatechin-3-gallate>gallic acid,
      epigallocatechin>epicatechin. Using gallic acid as a model tea phenolic and
      comparing it with the tea catechins and gallic acid-derivative food supplements,
      the major cytotoxic mechanism found with hepatocytes was mitochondrial membrane
      potential collapse and ROS formation. Epigallocatechin-3-gallate was also the
      most effective at collapsing the mitochondrial membrane potential and inducing
      ROS formation. Liver injury was also observed in vivo when these tea phenolics
      were administered ip to mice, as plasma alanine aminotransferase levels were
      significantly increased. In contrast, GSH conjugation, methylation, metabolism by
      NAD(P)H:quinone oxidoreductase 1, and formation of an iron complex were important
      in detoxifying the gallic acid. In addition, for the first time, the GSH
      conjugates of gallic acid and epigallocatechin-3-gallate have been identified
      using mass spectrometry. These results add insight into the cytotoxic and
      cytoprotective mechanisms of the simple tea phenolic acids and the more complex
      tea catechins.

PMID- 16458188
TI  - Inhibition of sphingosine-1-phosphate- and vascular endothelial growth factor
      induced endothelial cell chemotaxis by red grape skin polyphenols correlates with
      a decrease in early platelet-activating factor synthesis.
AB  - Vascular endothelial growth factor (VEGF) and platelet-derived lipid sphingosine
      1-phosphate (S1P) are two proinflammatory mediators which contribute to
      angiogenesis, in part through the synthesis of platelet-activating factor (PAF).
      The red grape skin polyphenolic extract (SGE) both prevents and inhibits
      angiogenesis in the Matrigel model, decreases the basal motility of endothelial
      and cancer cells, and reverses the chemotactic effect of S1P and VEGF on bovine
      aortic endothelial cells (BAECs) as well as the chemotactic effect of conditioned
      medium on human HT-1080 fibrosarcoma, human U-87 glioblastoma, and human DAOY
      medulloblastoma cells. Inhibition of VEGF- and S1P-mediated chemotaxis by SGE is
      associated with a down-regulation of ERK and p38/MAPK phosphorylation and a
      decreased in acute PAF synthesis. Notably, as do extracellular inhibitors of PAF
      receptor, SGE prevents S1P-induced PAF synthesis and the resulting activation of
      the S1P/endothelial differentiation gene-1 cascade. Given the key role of VEGF
      and S1P in inflammation, angiogenesis, and tumor invasion, SGE may therefore
      contribute to prevent (or to delay) the development of diseases associated with
      angiogenesis dysregulation, including cancer. The dual inhibition of S1P- and
      VEGF-mediated migration of endothelial cell and of serum-stimulated migration of
      U-87 cells suggests a usefulness of SGE against highly invasive human
      glioblastoma.

PMID- 16458189
TI  - Vitamin C prophylaxis promotes oxidative lipid damage during surgical ischemia
      reperfusion.
AB  - Reactive oxygen species (ROS) have been implicated in the cellular membrane
      damage and postoperative morbidity associated with obligatory ischemia
      reperfusion (I-R) during vascular surgery. Thus, a clinical study was undertaken
      to evaluate the effects of ascorbate prophylaxis on ROS exchange kinetics in 22
      patients scheduled for elective abdominal aortic aneurysm (AAA) or infra-inguinal
      bypass (IIB) repair. Patients were assigned double-blind to receive intravenous
      sodium ascorbate (2 g vitamin C, n=10) or placebo (0.9% saline, n=12)
      administered 2 h prior to surgery. Blood samples were obtained from the arterial
      and venous circulation proximal to the respective sites of surgical repair
      (local) and from an antecubital vein (peripheral) during cross-clamping
      (ischemia) and within 60 s of clamp release (reperfusion). Ascorbate
      supplementation increased the venoarterial concentration difference (v-adiff) of
      lipid hydroperoxides (LH), interleukin (IL)-6 and vascular endothelial growth
      factor (VEGF) protein during ischemia. This increased the peripheral
      concentration of LH, total creatine phosphokinase (CPK), and VEGF protein during
      reperfusion (P<0.05 vs placebo). Electron paramagnetic resonance (EPR)
      spectroscopy confirmed that free iron was available for oxidative catalysis in
      the local ischemic venous blood of supplemented patients. An increased
      concentration of the ascorbate radical (A.-) and alpha-phenyl-tert-butylnitrone
      (PBN) adducts assigned as lipid-derived alkoxyl (LO.) and alkyl (LC.) species
      were also detected in the peripheral blood of supplemented patients during
      reperfusion (P<0.05 vs ischemia). In conclusion, these findings suggest that
      ascorbate prophylaxis may have promoted iron-induced oxidative lipid damage via a
      Fenton-type reaction initiated during the ischemic phase of surgery. The
      subsequent release of LH into the systemic circulation may have catalyzed
      formation of second-generation radicals implicated in the regulation of vascular
      permeability and angiogenesis.

PMID- 16458190
TI  - Increased sensitivity to asbestos-induced lung injury in mice lacking
      extracellular superoxide dismutase.
AB  - Asbestosis is a chronic form of interstitial lung disease characterized by
      inflammation and fibrosis that results from the inhalation of asbestos fibers.
      Although the pathogenesis of asbestosis is poorly understood, reactive oxygen
      species may mediate the progression of this disease. The antioxidant enzyme
      extracellular superoxide dismutase (EC-SOD) can protect the lung against a
      variety of insults; however, its role in asbestosis is unknown. To determine if
      EC-SOD plays a direct role in protecting the lung from asbestos-induced injury,
      intratracheal injections of crocidolite were given to wild-type and ec-sod-null
      mice. Bronchoalveolar lavage fluid (BALF) from asbestos-treated ec-sod-null mice
      at 24 h, 14 days, or 28 days posttreatment showed increased inflammation and
      total BALF protein content compared to that of wild-type mice. In addition, lungs
      from ec-sod-null mice showed increased hydroxyproline content compared to those
      of wild-type mice, indicating a greater fibrotic response. Finally, lungs from ec
      sod-null mice showed greater oxidative damage, as assessed by nitrotyrosine
      content compared to those of their wild-type counterparts. These results indicate
      that depletion of EC-SOD from the lung increases oxidative stress and injury in
      response to asbestos.

PMID- 16458191
TI  - Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil
      phenolic compounds in humans.
AB  - Olive oil phenolic compounds are potent antioxidants in vitro, but evidence for
      antioxidant action in vivo is controversial. We examined the role of the phenolic
      compounds from olive oil on postprandial oxidative stress and LDL antioxidant
      content. Oral fat loads of 40 mL of similar olive oils, but with high (366
      mg/kg), moderate (164 mg/kg), and low (2.7 mg/kg) phenolic content, were
      administered to 12 healthy male volunteers in a cross-over study design after a
      washout period in which a strict antioxidant diet was followed. Tyrosol and
      hydroxytyrosol, phenolic compounds of olive oil, were dose-dependently absorbed
      (p<0.001). Total phenolic compounds in LDL increased at postprandial state in a
      direct relationship with the phenolic compounds content of the olive oil ingested
      (p<0.05). Plasma concentrations of tyrosol, hydroxytyrosol, and 3-O-methyl
      hydroxytyrosol directly correlated with changes in the total phenolic compounds
      content of the LDL after the high phenolic compounds content olive oil ingestion.
      A 40 mL dose of olive oil promoted a postprandial oxidative stress, the degree of
      LDL oxidation being lower as the phenolic content of the olive oil administered
      increases. In conclusion, olive oil phenolic content seems to modulate the LDL
      phenolic content and the postprandial oxidative stress promoted by 40 mL olive
      oil ingestion in humans.

PMID- 16458192
TI  - Synergistic protection by S-adenosylmethionine with vitamins C and E on liver
      injury induced by thioacetamide in rats.
AB  - Free radicals are involved in the pathogenesis of acute liver injury induced by
      thioacetamide (TAA). We investigated the effects of S-adenosylmethionine (SAMe)
      combined with/without vitamins C and E on TAA-induced acute liver injury in rats.
      TAA was given intraperitoneally (200 mg kg-1). Antioxidant treatments (SAMe, 25
      mg kg-1; vitamin C, 100 mg kg-1; vitamin E, 200 mg kg-1, intraperitoneal) were
      given 1 h later. Liver histology, enzymology, and ability to release hepatic
      insulin-sensitizing substance (HISS) were assessed. TAA caused liver tissue
      injury, increased liver enzymes, and decreased insulin sensitivity (p<0.01).
      Blockade of HISS release by atropine did not further decrease insulin sensitivity
      in rats with TAA insult, indicating that the decrease in insulin sensitivity was
      HISS dependent. Treatment with SAMe alone or vitamins C+E slightly improved liver
      histology but not the changes in liver enzymes and insulin sensitivity. Combined
      treatment with SAMe plus vitamins C+E greatly protected the liver from tissue
      injury, the increase in liver enzymes, and the decrease in insulin sensitivity.
      In conclusion, acute liver injury causes HISS-dependent insulin resistance
      (HDIR). There are synergistic antioxidative effects among the antioxidants, SAMe
      and vitamins C and E, that protect the liver from TAA-induced HDIR, suggesting
      that antioxidant treatment may best be done using a balanced "cocktail."

PMID- 16458193
TI  - Effect of nitrosative stress on Schizosaccharomyces pombe: inactivation of
      glutathione reductase by peroxynitrite.
AB  - Oxidative stress has been shown to alter cellular redox status in various cell
      types. Changes in expressions of several antioxidative and antistress-responsive
      genes along with activation or inactivation of various proteins were also
      reported during oxidative insult as well as during nitrosative stress. In the
      present study, we show the effect of nitrosative stress on cellular redox status
      of fission yeast Schizosaccharomyces pombe. This is the first report of S
      nitrosoglutathione (GSNO) reductase activity in S. pombe and its inactivation by
      GSNO. We also show the inactivation of glutathione reductase (GR) and glutathione
      peroxidase in the presence of various reactive nitrogen species in vivo. In
      addition, we first observe the inactivation of GR by peroxynitrite in vivo using
      S. pombe cells and also similar observations under in vitro conditions. An
      immunoreactive band against monoclonal anti-3-nitrotyrosine antibody confirms the
      modification of GR under in vitro conditions. We also show the effect of
      nitrosative stress on Deltapap1 cells of S. pombe, which are more sensitive to
      nitrosative stress, indicating the involvement of Pap1 in the protection against
      nitrosative stress. Finally, exposure of S. pombe cells to reactive nitrogen
      species reveals an important role of cellular thiol pool in protection against
      nitrosative stress.

PMID- 16458194
TI  - Inhibition of human neutrophil oxidative burst by pyrazolone derivatives.
AB  - The risk of agranulocytosis associated with the use of pyrazolone drugs at
      therapeutical doses and for short periods of time has been considered to be very
      low. However, little or no attention at all has been devoted to the possible
      hindrance of neutrophil burst and scavenging of neutrophil-generated reactive
      oxygen species (ROS) by these compounds. Such an effect could be beneficial in
      the case of overactivation of neutrophils but could also be highly detrimental if
      the number of circulating neutrophils is already decreased. Thus, the aim of the
      present study was to evaluate the putative inhibitory effect of the pyrazolones
      dipyrone, aminopyrine, isopropylantipyrine, and antipyrine against human
      neutrophil burst and their scavenging activity against O2.-, H2O2, HO., ROO., and
      HOCl. The obtained results showed that dipyrone and aminopyrine prevent phorbol
      12-myristate-13-acetate-induced neutrophil burst with high efficiency, while
      isopropylantipyrine had little effect and antipyrine had no effect at all.
      Dipyrone and aminopyrine were highly potent scavengers of HO. and HOCl, while, in
      accordance with the neutrophil burst results, isopropylantipyrine had little
      effect and antipyrine had no effect at all against these two ROS. None of the
      studied pyrazolones was capable of scavenging O2.- or H2O2, while dipyrone was
      shown to be the most reactive against ROO..

PMID- 16458195
TI  - Ultraviolet A induces apoptosis via reactive oxygen species in a model for Smith
      Lemli-Opitz syndrome.
AB  - Solar ultraviolet A (UVA) radiation induces many responses in skin including
      oxidative stress, DNA damage, inflammation, and skin cancer. Smith-Lemli-Opitz
      syndrome (SLO-S) patients show dramatically enhanced immediate (5 min) and
      extended (24-48 h) skin inflammation in response to low UVA doses compared to
      normal skin. Mutations in Delta7-dehydrocholesterol reductase, which converts 7
      dehydrocholesterol to cholesterol, produces high levels of 7-dehydrocholesterol
      in SLO-S patient's serum. Since 7-dehydrocholesterol is more rapidly oxidized
      than cholesterol, we hypothesized that 7-dehydrocholesterol enhances UVA-induced
      oxidative stress leading to keratinocyte death and inflammation. When
      keratinocytes containing high 7-dehydrocholesterol and low cholesterol were
      exposed to UVA (10 J/cm2), eightfold greater reactive oxygen species (ROS) were
      produced than in normal keratinocytes after 15 min. UVA induced 7
      dehydrocholesterol concentration-dependent cell death at 24 h. These responses
      were inhibited by antioxidants, reduced nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase inhibitor (diphenyleneiodonium) and a mitochondria
      specific radical quencher. Cell death was characterized by activation of caspases
      3, -8, and -9 and by phosphatidylserine translocation. Studies using antioxidants
      and specific caspase inhibitors indicated that activation of caspase-8, but not
      caspase-9, mediates ROS-dependent caspase-3 activation and suggested that ROS
      from NADPH oxidase activate caspase-8. These results support a ROS-mediated
      apoptotic mechanism for the enhanced UVA-induced inflammation in SLO-S patients.

PMID- 16458196
TI  - Redox-regulated cochaperone activity of the human DnaJ homolog Hdj2.
AB  - The human DnaJ homolog Hdj2 is a cochaperone containing a cysteine-rich zinc
      finger domain. We identified a specific interaction of Hdj2 with the cellular
      redox enzyme thioredoxin using a yeast two-hybrid assay and a
      coimmunoprecipitation assay, thereby investigating how the redox environment of
      the cell regulates Hdj2 function. In reconstitution experiments with Hsc70, we
      found that treatment with H2O2 caused the oxidative inactivation of Hdj2
      cochaperone activity. Hdj2 inactivation paralleled the oxidation of cysteine
      thiols and concomitant release of coordinated zinc, suggesting a role of cysteine
      residues in the zinc finger domain of Hdj2 as a redox sensor of chaperone
      mediated protein-folding machinery. H2O2-induced negative regulation of Hdj2
      cochaperone activity was also confirmed in mammalian cells using luciferase as a
      foreign reporter cotransfected with Hsc70 and Hdj2. The in vivo oxidation of
      cysteine residues in Hdj2 was detected only in thioredoxin-knockdown cells,
      implying that thioredoxin is involved in the in vivo reduction. The oxidative
      inactivation of Hdj2 was reversible. Wild-type thioredoxin notably recovered the
      oxidatively inactivated Hdj2 activity accompanied by the reincorporation of zinc,
      whereas the catalytically inactive mutant thioredoxin (Cys32Ser/Cys35Ser) did
      not. Taken together, we propose that oxidation and reduction reversibly regulate
      Hdj2 function in response to the redox states of the cell.

PMID- 16458197
TI  - Retinal degeneration from oxidative damage.
AB  - Paraquat, a herbicide that generates reactive oxygen species, has been used to
      probe the oxidative defense systems of lung. In this study, we investigated the
      effects of paraquat in the retina. There was no significant decline in
      electroretinogram (ERG) a- or b-wave amplitudes after intravitreous injection of
      1 mul of 0.5 mM paraquat in C57BL/6 mice, but loss of ERG function occurred after
      injection of 0.75 or 1 mM paraquat. Histology in paraquat-injected eyes showed
      condensation of chromatin and thinning of the inner and outer nuclear layers
      indicating cell death, and terminal deoxynucleotidyl transferase-mediated duTP
      biotinide end labeling demonstrated that one mechanism of cell death was
      apoptosis. Fluorescence in the retina and retinal pigmented epithelium after
      intraocular injection of paraquat followed by perfusion with hydroethidine
      indicated high levels of superoxide radicals, and oxidative damage was
      demonstrated by staining for acrolein and enzyme-linked immunosorbent assay for
      carbonyl adducts. Paraquat-induced damage to the outer nuclear layer was greater
      in BALB/c mice than in C57BL/6 mice, suggesting strain differences in the
      oxidative defense system of photoreceptors and/or other modifier genes.
      Intravitreous injection of paraquat provides a new model of oxidative damage
      induced retinal degeneration that is likely to be useful for testing new
      antioxidant treatments.

PMID- 16458198
TI  - Glutathione depletion in vivo enhances contraction and attenuates endothelium
      dependent relaxation of isolated rat aorta.
AB  - Ten-day administration of the glutamate-cysteine ligase inhibitor L-buthionine
      [S,R]-sulfoximine (BSO; 20 or 30 mM in drinking water) to adult male Sprague
      Dawley rats induced 50-60% glutathione depletion (p<0.001) and elevated aortic
      ring reactive oxygen species release and tissue and plasma H2O2 concentrations
      (p<0.001) compared to control animals (CON) that consumed normal drinking water.
      In contrast to previous studies using tail cuff plethysmography methods, BSO had
      no significant effect on systolic blood pressure assessed by indwelling femoral
      artery catheters in conscious animals (10-day values, 119+/-3 mn Hg vs 122+/-4 mm
      Hg in CON vs BSO, respectively). Thoracic aorta rings were excised for in vitro
      assessment of vasomotor function. BSO shifted the phenylephrine (PE) dose
      response curve to the left (p=0.003), lowering the EC50 for PE contraction (from 
      6.752+/-0.056 to -7.056+/-0.055 log units; p=0.001). Endothelium-dependent
      relaxation to acetylcholine (ACh) was significantly blunted (p=0.019) and the
      EC50 for ACh relaxation was significantly increased (from -7.428+/-0.117 to 
      7.129+/-0.048 log units; p=0.02) in BSO vs CON. Endothelium-independent
      vasorelaxation to sodium nitroprusside was similar in BSO and CON groups.
      Thoracic aorta immunoblot analyses revealed increases in endothelial nitric oxide
      synthase, superoxide dismutase 1 and 2, and soluble guanylate cyclase in BSO vs
      CON (all p<0.01). Thus, enhanced PE contraction, blunted endothelium-dependent
      relaxation, and adaptations in nitric oxide bioavailability pathways provide the
      first evidence of chronic, in vivo BSO-induced, oxidative stress-mediated direct
      effects on the vasomotor function of arteries.

PMID- 16458199
TI  - Nitric oxide protects the mitochondria of anterior pituitary cells and prevents
      cadmium-induced cell death by reducing oxidative stress.
AB  - Cadmium (Cd2+) is a highly toxic metal that affects the endocrine system. We have
      previously shown that Cd2+ induces caspase-3 activation and apoptosis of anterior
      pituitary cells and that endogenous nitric oxide (NO) protects these cells from
      Cd2+. Here we investigate the mechanisms by which NO exerts this protective role.
      Cd2+ (25 microM) reduced the mitochondrial membrane potential (MMP) as measured
      by flow cytometry. Cd2+-induced apoptosis was mitochondrial dependent since
      cyclosporin A protected the cells from this metal. Inhibition of NO synthesis
      with 0.5 mM L-NAME increased the effect of Cd2+ on MMP, whereas the NO donor
      DETANONOate (0.1 mM) reduced it. Cd2+ increased the production of reactive oxygen
      species (ROS) as measured by flow cytometry. This effect was electron-transfer
      chain-dependent since it was inhibited by rotenone. In fact, rotenone reduced the
      cytotoxic effect of the metal. The action of Cd2+ on mitochondrial integrity was
      ROS dependent. Trolox, an antioxidant, inhibited the effect of the metal on the
      MMP. Cd2+-induced increase in ROS generation was reduced by DETANONOate. There
      are discrepancies concerning the role of NO in Cd2+ toxicity. Here we show that
      NO reduces Cd2+ toxicity by protecting the mitochondria from oxidative stress in
      a system where NO plays a regulatory role.

PMID- 16458200
TI  - Faster plasma vitamin E disappearance in smokers is normalized by vitamin C
      supplementation.
AB  - Vitamin E disappearance is accelerated in cigarette smokers due to their
      increased oxidative stress and is inversely correlated with plasma vitamin C
      concentrations. Therefore, we hypothesized that ascorbic acid supplementation
      (500 mg, twice daily; 2 weeks) would normalize smokers' plasma alpha- and gamma
      tocopherol disappearance rates and conducted a double-blind, placebo-controlled,
      randomized crossover investigation in smokers (n=11) and nonsmokers (n=13) given
      a single dose of deuterium-labeled alpha- and gamma-tocopherols (50 mg each d6
      RRR-alpha and d2-RRR-gamma-tocopheryl acetate). During the placebo trial,
      smokers, compared with nonsmokers, had significantly (P<0.05) greater alpha- and
      gamma-tocopherol fractional disappearance rates and shorter half-lives. Ascorbic
      acid supplementation doubled (P<0.0001) plasma ascorbic acid concentrations in
      both groups and attenuated smokers', but not nonsmokers', plasma alpha- and gamma
      tocopherol (P<0.05) fractional disappearance rates by 25% and 45%, respectively.
      Likewise, smokers' plasma deuterium-labeled alpha- and gamma-tocopherol
      concentrations were significantly higher (P<0.05) at 72 h during ascorbic acid
      supplementation compared with placebo. Ascorbic acid supplementation did not
      significantly change (P>0.05) time of maximal or maximal-labeled alpha- and gamma
      tocopherol concentrations. Smokers' plasma F2alpha-isoprostanes were
      approximately 26% higher than nonsmokers (P>0.05) and were not affected by
      ascorbic acid supplementation in either group (P>0.05). In summary, cigarette
      smoking increased plasma alpha- and gamma-tocopherol fractional disappearance
      rates, suggesting that the oxidative stress from smoking oxidizes tocopherols and
      that plasma ascorbic acid reduces alpha- and gamma-tocopheroxyl radicals to
      nonoxidized forms, thereby decreasing vitamin E disappearance in humans.

PMID- 16458201
TI  - Sensitizer-mediated photooxidation of histidine residues: evidence for the
      formation of reactive side-chain peroxides.
AB  - Exposure of proteins to visible light in the presence of a sensitizer results in
      the oxidation of Met, Trp, Tyr, Cys, and His side chains. These reactions are
      only partially understood, particularly with His. In this study, the oxidation of
      free His, His derivatives, and His-containing peptides has been examined using
      visible light and a range of sensitizers. It is shown that photooxidation gives
      rise to unstable peroxides, in a light-, illumination time-, and sensitizer
      dependent manner. The yield of these materials is increased when reactions are
      carried out in solutions prepared with D2O, which prolongs the lifetime of 1O2,
      and decreased in the presence of the potent 1O2 scavenger azide, consistent with
      the involvement of this excited state. These peroxides have half-lives of hours,
      though the rate of decomposition is enhanced by elevated temperatures,
      reductants, and metal ions. Reducing metal ions catalyze the formation of
      radicals, which have been detected by EPR spin trapping. Structural analysis of
      His photo-products using NMR spectroscopy has provided evidence for the formation
      of oxygenated and cyclized compounds (e.g., 6a-hydroxy-2-oxo-octahydro
      pyrollo[2,3-d]imidazole-5-carboxylic acid) and cross-linked materials. The latter
      materials may be partly responsible for the high yield of aggregated materials
      detected on photooxidation of His-containing proteins.

PMID- 16458202
TI  - Analysis of urinary 8-nitroguanine, a marker of nitrative nucleic acid damage, by
      high-performance liquid chromatography-electrochemical detection coupled with
      immunoaffinity purification: association with cigarette smoking.
AB  - We have developed an analytical method to quantitate urinary 8-nitroguanine, a
      product of nitrative nucleic acid damage caused by reactive nitrogen species such
      as peroxynitrite and nitrogen dioxide. 8-Nitroguanine was purified from human
      urine using immunoaffinity columns with an anti-8-nitroguanine antibody, followed
      by quantitation by high-performance liquid chromatography-electrochemical
      detection. Four sequential electrodes were used to (a) oxidize interfering
      compounds (+250 mV), (b) reduce nitrated bases (two online electrodes at -1000
      mV), and (c) quantitate reduced derivatives (+150 mV). Using this system 8
      nitroxanthine can also be detected, with the detection limits being 25 and 50
      fmol/injection for 8-nitroguanine and 8-nitroxanthine, respectively. The method
      was used to analyze both adducts in the urine of smokers (n=12) and nonsmokers
      (n=17). We found that smokers excrete more 8-nitroguanine [median, 6.1 fmol/mg
      creatinine; interquartile range (IQR), 23.8] than nonsmokers (0; IQR, 0.90)
      (p=0.018), and although 8-nitroxanthine was detected in human urine, its level
      was not related to smoking status. This is the first report to show that 8
      nitroguanine is present in human urine and the methodology developed can be used
      to study the pathogenic roles of this adduct in the etiology of cancers
      associated with cigarette smoking and inflammation.

PMID- 16458203
TI  - Lipid peroxidation and renal cell carcinoma: further supportive evidence and new
      mechanistic insights.
AB  - We have recently proposed lipid peroxidation as a unifying mechanistic pathway by
      which several seemingly unrelated risk/protective factors (obesity, hypertension,
      diabetes, smoking, oophorectomy/hysterectomy, parity, antioxidants) affect renal
      cell carcinoma development. In experimental studies, increased lipid peroxidation
      is a principal mechanistic pathway in renal carcinogenesis induced by different
      chemicals. In this communication, we provide additional lines of evidence that
      further support a role for lipid peroxidation on renal cell cancer development.
      (1) Lipid peroxidation may explain the role of other risk (analgesic use, pre
      eclampsia) or protective (alcohol intake, oral contraceptives) factors for renal
      cell carcinoma. (2) Additional experimental evidence supports lipid peroxidation
      as an important mechanism in renal carcinogenesis, and (3) Existing evidence
      support a cross-talk between the lipid peroxidation pathway and other pathways
      that are relevant to renal carcinogenesis, such as apoptosis, VHL, and possibly
      other pathways.

PMID- 16458204
TI  - The value of teamwork.

PMID- 16458205
TI  - Perioperative outcome in adults undergoing elective deep hypothermic circulatory
      arrest with retrograde cerebral perfusion in proximal aortic arch repair:
      evaluation of protocol-based care.
AB  - OBJECTIVE: The purpose of this study was to describe perioperative outcome in
      adults undergoing elective proximal aortic arch repair with protocol-based deep
      hypothermic circulatory arrest (DHCA) with retrograde cerebral perfusion (RCP).
      DESIGN: Retrospective and observational. SETTING: Cardiothoracic operating rooms
      and intensive care unit. PARTICIPANTS: Seventy-nine consecutive adults undergoing
      elective proximal aortic arch repair with DHCA (1999-2001). INTERVENTIONS: None.
      MAIN RESULTS: Average age of the patients was 64.9 years. Mean circulatory arrest
      time was 30.4 +/- 8.5 minutes. Perioperative mortality was 7.6%. Perioperative
      stroke incidence was 3.8%. Tracheal extubation was successful in 87.3% of
      patients within 24 hours of operation. Of the cohort, 80.8% were discharged from
      the intensive care unit within 72 hours of surgery. Median length of hospital
      stay was 7.4 days. Repeat mediastinal exploration because of bleeding occurred in
      3.8% of patients. Although perioperative renal dysfunction (defined as >1.5-fold
      increase in plasma creatinine concentration) developed in 24.0% of patients, only
      3.8% required dialysis. CONCLUSIONS: The above parameters establish a baseline
      incidence for major perioperative complications in adults undergoing elective
      DHCA with RCP for elective proximal aortic arch repair. In approaching the open
      aortic arch for short periods of circulatory arrest, deep hypothermia with
      adjunctive RCP is safe and effective.

PMID- 16458206
TI  - Clinical predictors for prolonged intensive care unit stay in adults undergoing
      thoracic aortic surgery requiring deep hypothermic circulatory arrest.
AB  - OBJECTIVE: The purpose of this study was to describe clinical predictors for
      prolonged length of stay in the intensive care unit (PLOS-ICU) after adult
      thoracic aortic surgery requiring standardized deep hypothermic circulatory
      arrest (DHCA); and to determine the incidence of PLOS-ICU after DHCA, univariate
      predictors for PLOS-ICU, and multivariate predictors for PLOS-ICU. STUDY DESIGN:
      A retrospective and observational study. PLOS-ICU was defined as longer than 5
      days in the ICU. STUDY SETTING: Cardiothoracic operating rooms and the ICU.
      PARTICIPANTS: All adults requiring thoracic aortic repair with DHCA
      INTERVENTIONS: None. MAIN RESULTS: The cohort size was 144. The incidence of PLOS
      ICU was 27.8%. The mortality rate was 11.1%. Univariate predictors for PLOS-ICU
      were age, stroke, DHCA duration, vasopressor dependence >72 hours, mediastinal re
      exploration for bleeding, and renal dysfunction. Multivariate predictors for PLOS
      ICU were stroke, vasopressor dependence >72 hours, and renal dysfunction.
      CONCLUSIONS: PLOS-ICU after DHCA is common. The identified multivariate
      predictors merit further hypothesis-driven research to enhance perioperative
      protection of the brain, kidney, and cardiovascular system.

PMID- 16458207
TI  - Tracheostomy after major vascular surgery.
AB  - OBJECTIVES: Major vascular surgery such as aortic aneurysm repair may be
      associated with prolonged in-patient hospitalization. Certain patients undergo a
      tracheostomy to aid in weaning from mechanical ventilation or for secretion
      management. The authors hypothesized that tracheostomy after aortic
      reconstruction for aneurysmal disease was associated with poor outcomes. DESIGN:
      A retrospective, observational study. SETTING: Vascular surgical intensive care
      unit (ICU) of a tertiary referral hospital. PARTICIPANTS: Eighty-one patients who
      underwent a tracheostomy after open thoracoabdominal or abdominal aortic aneurysm
      (AAA) repair between 1993 and 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Of 1,940 patients who underwent aneurysm repair, 81 (4.2%) had a
      tracheostomy during their index hospitalization. Of those patients, 40.7% did not
      survive to hospital discharge. Postoperative sepsis was associated with an
      increased mortality (relative risk 2.45, 95% confidence interval [CI] 1.22-4.90).
      Many developed postoperative renal failure and were more likely to die in the
      hospital (relative risk 1.53, 95% CI 1.00-2.33). The preoperative diagnosis of
      chronic obstructive pulmonary disease (COPD) was not associated with increased
      mortality (relative risk 0.471, 95% CI 0.23-0.96). Thirty-two (39.5%) patients
      were transferred from the ICU to a chronic ventilator dependency unit (CVDU).
      CONCLUSIONS: Tracheostomy in patients after aortic reconstruction for aneurysmal
      disease is associated with a high incidence of in-hospital mortality. Patients
      who survive to ICU discharge are likely to be transferred to a CVDU for further
      respiratory management. The preoperative diagnosis of COPD is associated with
      improved survival, whereas postoperative sepsis is associated with an increased
      mortality. These observations should be considered when counseling patients and
      their families regarding tracheostomy after aortic surgery.

PMID- 16458208
TI  - Detection and monitoring of complications associated with femoral or axillary
      arterial cannulation for surgical repair of aortic dissection.
AB  - OBJECTIVES: Femoral arterial perfusion can be associated with complications, and
      axillary arterial perfusion is not free from risk. The purpose of this study was
      to describe the incidence and complications of femoral versus axillary artery
      cannulation for surgical repair of aortic dissection and to devise a strategy for
      early detection and monitoring of complications using transesophageal
      echocardiography, near-infrared spectroscopy, and orbital Doppler. DESIGN:
      Retrospective and observational. SETTING: University hospital. PARTICIPANTS:
      Seventy-five consecutive patients with aortic dissection who underwent aortic
      repair between 1995 and 2004. INTERVENTIONS: Aortic surgery. MEASUREMENTS AND
      MAIN RESULTS: Among the 44 cases with femoral arterial perfusion, sudden onset of
      hypotension occurred in 3 cases but was immediately treated based on the TEE
      diagnosis (collapse of true lumen in the descending aorta). In another case,
      myocardial ischemia occurred because of occlusion of the coronary artery. These
      four cases comprised 57.1% of 7 patients with type III dissection with retrograde
      extension in whom femoral arterial perfusion was used. However, malperfusion was
      not encountered in 3 cases of the same type of dissection but with axillary
      arterial perfusion. Axillary artery perfusion (29 cases) led to malperfusion of
      the right frontal lobe and coronary artery in 1 case each. CONCLUSIONS: Flexible
      management guided by real-time information is essential. Upon initiating femoral
      arterial perfusion, malperfusion should first be checked for in the descending
      aorta and then in the coronary and visceral arteries, especially in cases of type
      III dissection with retrograde extension. Attention should be paid to cerebral
      and coronary malperfusion when initiating axillary arterial perfusion.

PMID- 16458209
TI  - Cardiac output measurement during infrarenal aortic surgery: echo-esophageal
      Doppler versus thermodilution catheter.
AB  - OBJECTIVE: Aortic surgery is associated with various hemodynamic and cardiac
      output modifications. These disorders may be partly caused by blood flow
      redistribution between supra-aortic and descending aorta regions during clamping
      and unclamping. A new echo-esophageal Doppler (Hemosonic 100; Arrow, Reading, PA)
      calculates cardiac output from a simultaneous measurement of blood flow velocity
      and diameter of the descending aorta. This calculation may be affected by blood
      redistribution during aortic clamping. The aim of this study was to compare
      cardiac output measured by echo-esophageal Doppler and by bolus thermodilution
      catheter during infrarenal aortic surgery. DESIGN: Prospective, observational
      study. SETTING: University hospital, single institution. PARTICIPANTS: Twenty-two
      adult patients. INTERVENTIONS: Infrarenal aortic surgery. MEASUREMENTS AND MAIN
      RESULTS: Cardiac outputs monitored by both devices were highly correlated during
      the whole surgical procedure (r2 ranging from 0.54 to 0.76). Bland and Altman
      analysis showed absence of significant bias before and after clamping (ranging
      from 0.1 +/- 0.73 L/min to 0.18 +/- 1 L/min, p > 0.05) and a significant bias of
      0.5 +/- 1.05 L/min (p < 0.05) during aortic clamping. Limits of agreement did not
      differ significantly during the whole surgical procedure (ranging from -1.36/2.19
      to -2.23/2.49). During clamping and unclamping, changes in cardiac output
      obtained by both methods were positively correlated (r2 = 0.7). CONCLUSIONS: Bias
      between both methods was clinically acceptable, and limits of agreement were not
      significantly modified by aortic clamping. However, larger studies including
      homogenous aortic pathologies are necessary to validate this method during
      infrarenal aortic surgery.

PMID- 16458210
TI  - Methicillin-resistant Staphylococcus species in a cardiac surgical intensive care
      unit: a 5-year experience.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus is a growing problem in
      intensive care units (ICUs). The aim of this study was to describe the
      epidemiology of methicillin-resistant Staphylococcus isolates in a cardiac
      surgical ICU over a 5-year period and to determine the risk factors and outcome
      of this condition. METHODS: During the period from January 1998 to July 2003, the
      clinical data of all adult patients who underwent cardiac surgery in a university
      hospital were prospectively recorded in a database; the perioperative clinical
      variables and microbiologic data were studied by means of univariate and
      multivariate analysis in order to identify risk factors for the development of
      methicillin resistance and in-hospital death. RESULTS: Methicillin-resistant
      Staphylococcus species strains were isolated in 118 of 6,423 patients operated on
      during the study period (7.6 cases per 1,000 days of ICU stay), with a constant
      prevalence rate throughout the years. Methicillin-resistant Staphylococcus
      species have been the most frequently isolated microorganisms in the authors'
      ICU; 75% of Staphylococcus aureus and 95% of coagulase-negative staphylococci
      were methicillin resistant. In-hospital mortality in methicillin-resistant
      Staphylococcus-positive patients was 50.0% (59/118), whereas it was 1.7%
      (108/6305) in other patients (p < 0.0001). On multivariate analysis, methicillin
      resistant Staphylococcus species isolation was the single risk factor with the
      strongest association with in-hospital death (odds ratio, 8.5; 95% confidence
      interval 4.9-14.7). In the present series, there were no isolates of vancomycin
      resistant species (Enterococcus species or Staphylococcus species). CONCLUSIONS:
      Staphylococcus species represent the most frequently isolated microorganisms in
      the authors' ICU. In-hospital mortality in cardiac surgical patients is strongly
      correlated to the isolation of methicillin-resistant Staphylococcus.

PMID- 16458211
TI  - Low arterial saturation is associated with increased sensitivity to activated
      protein C in children with congenital heart disease.
AB  - OBJECTIVES: Children with congenital heart disease experience both hemorrhagic
      and thrombotic complications. In this report the authors test the hypothesis that
      hypoxemia is associated with altered sensitivity to activated protein C (aPC) in
      pediatric patients with congenital heart lesions. DESIGN: A retrospective genetic
      registry review, with statistical evaluation of factors contributing to the aPC
      ratio. SETTING: Large university hospital. PARTICIPANTS: Cohort of 92 children
      with congenital heart disease undergoing cardiac catheterization procedures.
      INTERVENTIONS: The authors measured the aPC ratio at cardiac catheterization and
      evaluated the contribution of independent variables using linear regression and
      classification tree approaches. Independent variables included age, gender, use
      of aspirin, history of thrombosis, room air arterial saturation, factor VIII:C
      levels, presence of congestive heart failure, and heterozygosity for factor V
      Leiden. MEASUREMENTS AND MAIN RESULTS: At univariate analysis, factor V Leiden,
      female gender, room air arterial saturation, age greater than 6 months, and
      plasma factor VIII:C levels were associated with a lower aPC ratio (resistance to
      aPC). At stepwise linear regression, arterial saturation, factor VIII:C level,
      female gender, and factor V Leiden were independently associated with a lower aPC
      ratio, and these variables explained about 49% of the variability in aPC ratio.
      The classification tree approach confirmed the dependence of aPC ratio on factor
      V genotype and arterial saturation. CONCLUSIONS: The aPC ratio in this population
      is associated with hypoxemia, independent of factors previously observed in
      adults. Further studies are under way to determine how aPC resistance or
      sensitivity may independently affect perioperative hemostasis in this population.

PMID- 16458212
TI  - Serum lactate level has prognostic significance after pediatric cardiac surgery.
AB  - OBJECTIVE: The determination of postoperative course after cardiac surgery has
      always been a challenging issue. It is more sophisticated in the pediatric age
      group. The aim of this investigation was to identify whether increased
      concentrations of lactate in arterial blood has a predictive value for
      postoperative morbidity and mortality after heart surgery. METHODS: From May 2002
      to June 2003, 60 infants operated on at the authors' institution were included in
      this prospective study. The patients were divided into 2 groups according to
      their respective postoperative serum lactate values. After the stabilization
      period in the intensive care unit (first 3 hours postoperatively), samples for
      serum lactate were obtained from arterial blood at 3 (t1), 6 (t2), and 12 hours
      (t3) postoperatively. The patients were subdivided into 2 groups according to
      their respective mean serum lactate values. A value of 4.8 mmol/L (3 times the
      normal upper limit) was chosen as a threshold for serum lactate. The patients
      with a mean value of greater than 4.8 mmol/L (group 1) were compared with the
      remaining group of patients (group 2). The relationship between serum mean
      lactate level and intraoperative and postoperative clinical variables was
      evaluated. RESULTS: Among the patients in this study, 26 (43.3%) had a serum mean
      lactate level more than 4.8 mmol/L and 34 (56.7%) had a level of 4.8 mmol/L or
      less. Age, aortic cross-clamping time, cardiopulmonary bypass time, and the
      lowest hematocrit during cardiopulmonary bypass were significant variables that
      influenced the postoperative serum mean lactate level. Six patients died in the
      postoperative period and 54 infants survived. The hospital mortality was
      significantly higher in group 1 than in group 2 (19.0% v 2.9%; p = 0.037, kappa =
      0.179). Multivariate analysis revealed that serum mean lactate level correlated
      significantly with inotrope score, intubation time, and intensive care unit stay.
      CONCLUSIONS: Blood lactate concentration of 4.8 mmol/L or higher during the early
      postoperative hours identifies a group of patients with increased risk of
      postoperative morbidity and mortality.

PMID- 16458213
TI  - Direct versus guidewire-assisted pediatric radial artery cannulation technique.
AB  - OBJECTIVE: Radial artery cannulation is a more difficult procedure in pediatric
      patients. Direct technique commonly fails in these patients, and several
      techniques have been developed for successful arterial cannulation. The purpose
      of this study was to compare direct radial artery cannulation with guidewire
      assisted cannulation in children undergoing cardiac or aortic surgery. The
      hypothesis was that the guidewire-assisted technique would lead to fewer attempts
      and provide better long-term blood pressure monitoring and blood sampling.
      MATERIALS AND METHODS: One hundred pediatric patients with congenital heart
      defects undergoing major cardiovascular surgery, who required a radial artery
      catheter, were included in the study. Patients were divided into 2 groups: group
      1 included 50 patients who had radial artery cannulation with the direct
      technique, and group 2 included 50 patients who had a guidewire-assisted radial
      artery cannulation. RESULTS: A radial artery was successfully cannulated in 48
      patients in group 2 but only 38 patients in group 1. Mean elapsed time for radial
      artery cannulation was 22 +/- 4.6 minutes in group 1 and 7 +/- 4.2 minutes in
      group 2 (p = 0.001). The average number of attempts for cannulation was 4.5 in
      group 1 and 2.1 in group 2 (p = 0.022). The opposite radial or an alternative
      artery was used more commonly in the direct technique group. Satisfactory blood
      pressure monitoring and sampling of blood were obtained in 28 patients in group 1
      and 46 patients in group 2 (p < 0.001). CONCLUSION: The authors recommend the use
      of a guidewire-assisted radial artery cannulation technique rather than a direct
      technique. The guidewire-assisted technique provided easy, safe, and quick
      cannulation and allowed for long-term satisfactory blood pressure monitoring and
      blood sampling because of the longer length of the Teflon catheter advanced into
      the artery over the guidewire, and a low rate of dissection of the radial artery.

PMID- 16458214
TI  - Postoperative white blood cell count predicts atrial fibrillation after cardiac
      surgery.
AB  - BACKGROUND: Postoperative atrial fibrillation (AF) occurs in as many as 50% of
      cardiac surgery patients and represents the most common postoperative rhythm
      complication. The cause of AF after cardiac surgery is incompletely understood,
      and its prevention remains suboptimal. Currently the role of inflammation and
      oxidative stress on electrical remodeling is under investigation, and recent
      studies have demonstrated that C-reactive protein levels are elevated in AF. The
      purpose of the present study was to investigate the correlation between the
      postoperative white blood cell (WBC) count as a marker of inflammation and the
      development of postoperative AF after cardiac surgery. METHODS AND RESULTS:
      Patients undergoing elective cardiac surgery in the absence of significant left
      ventricular dysfunction (n = 253; average age, 65 +/- 11 years) were recruited to
      the present prospective study. Atrial fibrillation developed during the
      postoperative period in 99 patients (39.1%) of the total study population. The
      WBC count was prospectively assessed in all patients to determine the predictive
      value of baseline and postoperative WBC count on development of postoperative AF.
      Baseline WBC count was 6.8 +/- 1.9 x 10(9)/L and 6.8 +/- 2.2 x 10(9)/L (p =
      0.95), respectively, in patients with and without postoperative AF; and
      postoperative peak WBC count was 16.3 +/- 6.5 x 10(9)/L and 15 +/- 4.2 x 10(9)/L
      (p = 0.048), respectively, in patients without postoperative AF. However, neither
      baseline nor peak monocyte count differed significantly among patients with and
      without postoperative AF: 0.43 +/- 0.15 x 10(9)/L and 0.46 +/- 0.46 x 10(9)/L (p
      = 0.5), and 0.91 +/- 0.3 x 10(9)/L and 0.93 +/- 0.4 x 10(9)/L (p = 0.8),
      respectively. In addition to a more pronounced increase in peak WBC count (above
      v below median; odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; p <
      0.05), increasing age (above v below median; OR, 2.6; CI, 1.2-3.9; p < 0.01),
      surgery for valvular heart disease versus coronary artery bypass grafting (OR,
      2.8; CI, 1.1-3.5; p < 0.01), development of postoperative complications, such as
      stroke, infections, or unstable hemodynamics (OR, 1.9; CI, 1.0-7.5; p < 0.05),
      and perioperative nonuse of beta-adrenergic blockers (OR, 1.7; CI, 1.1-4.9; p <
      0.05) were identified as independent predictors of postoperative AF by
      multivariate logistic regression analysis. CONCLUSIONS: Cardiac surgery is
      associated with an elevated postoperative WBC count that represents a common
      marker of inflammation. A more pronounced increase in postoperative WBC count
      independently predicts development of postoperative AF. These data provide
      additional evidence to support the association between the inflammatory response
      and postoperative AF.

PMID- 16458215
TI  - Inclusion of sevoflurane in cardioplegia reduces neutrophil activity during
      cardiopulmonary bypass.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of sevoflurane
      cardioplegia on neutrophil response and complement activation after
      cardiopulmonary bypass (CPB). DESIGN: A prospective, randomized clinical
      investigation. SETTING: University-affiliated hospital; single institutional.
      PARTICIPANTS: Twenty-one male patients undergoing coronary bypass surgery using
      CPB. INTERVENTIONS: Eleven patients were randomly assigned to receive sevoflurane
      2% as a part of the cardioplegic mixture (SEV). The control group (n = 10)
      received no sevoflurane in their cardioplegia (control). MEASUREMENTS AND MAIN
      RESULTS: Myeloperoxidase activity (MPO) was assayed in coronary sinus blood as a
      surrogate for neutrophilic response at the termination of CPB. MPO activity in
      the coronary sinus blood was lower in the patients who received sevoflurane
      compared with controls. MPO activity was higher in patients with cardiac events
      at 4-year follow-up when compared with asymptomatic patients. IL-8, C4b, C3d,
      C5a, and CH50 were assessed in coronary sinus and peripheral blood at time of CPB
      initiation (T0) and upon the termination of CPB (T2). Peripheral blood sampling
      occurred at the sixth hour after T0 (T6). IL-8 levels were significantly
      inhibited in the SEV group when compared with controls at T2 and T6. CH50 (an
      index of global activation of complement system) decreased 30% at T2 and 52% at
      T6. The classic component of the complement pathway (C4b) was effectively
      inhibited in the SEV group, whereas the common pathway (C3d and C5a) was similar
      in both groups. CONCLUSIONS: The addition of sevoflurane to cardioplegia is
      associated with an inhibition of neutrophils after CPB. A major component of the
      neutrophil response appears to be IL-8 mediated, although the classic complement
      pathway is also inhibited by sevoflurane.

PMID- 16458216
TI  - The effect of cardiopulmonary bypass on the expression of inducible nitric oxide
      synthase, endothelial nitric oxide synthase, and vascular endothelial growth
      factor in the internal mammary artery.
AB  - OBJECTIVE: Endothelial function of a vessel may be impaired by local or systemic
      inflammation initiated by cardiopulmonary bypass (CPB) during coronary artery
      bypass graft (CABG) surgery. The present study was designed to investigate the
      early effects of CPB on nitric oxide production and vascular endothelial growth
      factor (VEGF) expression in internal mammary artery (IMA). DESIGN: Prospective
      study. SETTING: University hospital. PARTICIPANTS: Twenty patients who were
      scheduled for elective CABG with CPB. INTERVENTIONS: IMA sections were studied
      immunohistochemically from these patients. The samples were taken from the distal
      end of the IMA before the institution of CPB and just before the construction of
      the IMA-left anterior descending artery anastomosis. MEASUREMENT AND MAIN
      RESULTS: After CPB, VEGF and endothelial nitric oxide synthase immunoreactivity
      increased significantly when compared with baseline values in the endothelium (p
      = 0.0156, p = 0.0313) and adventitia (p = 0.0313, p = 0.0001), respectively. No
      significant change was observed in inducible nitric oxide synthase
      immunoreactivity. CONCLUSIONS: The increase in eNOS expression may have been
      induced by the inflammation caused by CPB.

PMID- 16458217
TI  - Inaccuracy of BIS values produced by the cardiopulmonary bypass machine during
      the operative repair of an aortic dissection.

PMID- 16458218
TI  - Abdominal compartment syndrome after sepsis in an infant with congenital heart
      disease.

PMID- 16458219
TI  - Bilateral phrenic nerve palsy in a neonate following complex congenital cardiac
      surgery.

PMID- 16458220
TI  - Successful management of a case of massive air embolism from cardiopulmonary
      bypass with retrograde cerebral perfusion in a child.

PMID- 16458221
TI  - Levosimendan in severe right ventricular failure following mitral valve
      replacement.

PMID- 16458222
TI  - Rare mechanical complications during pulmonary artery catheterization with a
      continuous cardiac output catheter.

PMID- 16458223
TI  - Right atrial perforation resulting from pulmonary artery catheter insertion
      during coronary artery bypass surgery.

PMID- 16458224
TI  - Utility of intraoperative transesophageal echocardiography in an atrial septal
      defect operation.

PMID- 16458225
TI  - TEE-guided one-stage excision of intravenous leiomyomatosis with cardiac
      extension through an abdominal approach.

PMID- 16458226
TI  - Diagnosis of left atrial appendage thrombus in the presence of sinus rhythm with
      the aid of transesophageal echocardiography during coronary artery bypass
      grafting.

PMID- 16458227
TI  - Volume therapy in cardiac surgery: are Americans different from Europeans?

PMID- 16458228
TI  - Case 1-2006: off-pump coronary artery bypass graft surgery anticoagulation with
      bivalirudin: a patient with heparin-induced thrombocytopenia syndrome type II and
      renal failure.

PMID- 16458229
TI  - Pro: Should aspirin be continued after cardiac surgery in the setting of
      thrombocytopenia?

PMID- 16458230
TI  - Con: Should aspirin be continued after cardiac surgery in the setting of
      thrombocytopenia?

PMID- 16458231
TI  - A couple of long intervals in intraoperative cardiac pacing.

PMID- 16458232
TI  - Is the mass an abnormal left atrial appendage?

PMID- 16458233
TI  - Use of cerebrospinal fluid drainage catheters during single-stage
      transmediastinal repair of ascending and descending aortic aneurysms.

PMID- 16458236
TI  - Resource utilization in on- and off-pump coronary artery surgery: factors
      influencing postoperative length of stay--an experience of 1,746 consecutive
      patients undergoing fast-track cardiac anesthesia.

PMID- 16458237
TI  - Silbronco double-lumen tube.

PMID- 16458238
TI  - Resection of the Arndt Bronchial Blocker during stapler resection of the left
      lower lobe.

PMID- 16458239
TI  - "Do not go gentle into that good night"--Dylan Thomas.

PMID- 16458240
TI  - What's new in paraoptometric certification?

PMID- 16458241
TI  - Preventing reactivation of ocular histoplasmosis: guidance for patients at risk.
AB  - BACKGROUND: Ocular histoplasmosis syndrome (OHS), a significant cause of vision
      loss in young and middle-aged adults, is associated with the fungus Histoplasma
      capsulatum (Hc). There is considerable evidence that recurrent reactivation of
      perimacular ocular histoplasmosis lesions is an important cause of disease
      progression and that vision loss is at least, in part, a consequence of host
      sensitivity to fungal antigen. METHODS: The etiology and pathogenesis of OHS is
      reviewed and specific recommendations are made for patients with OHS that may
      decrease the risk of reactivation of ocular histoplasmosis lesions and slow
      disease progression. CONCLUSION: Patients with perimacular chorioretinal scars
      secondary to OHS should be informed by the clinician that they are at risk for
      vision loss; they should be told the symptoms of choroidal neovascularization and
      how to self-monitor their vision with an Amsler grid. We recommend they also be
      instructed on how to decrease their risk of reinfection by Hc. Aggressive
      treatment of dermatomycoses, onychomycosis, vaginal candidiasis, and other
      chronic fungal infections may decrease the risk of reactivation of ocular
      lesions. Patients with OHS who are considering LASIK surgery should be informed
      that the procedure may trigger choroidal neovascularization.

PMID- 16458242
TI  - Gas permeable toric use and applications: survey of Section on Cornea and Contact
      Lens Diplomates of the American Academy of Optometry.
AB  - BACKGROUND: The purpose of this study was to survey Diplomates in the Section on
      Cornea and Contact Lenses of the American Academy of Optometry (AAO) to determine
      their fitting preferences for astigmatic patients, lens materials used, and their
      perception of simplicity or complexity of bitoric fitting. METHODS: A total of
      180 practitioners, representing all active Diplomates in the Cornea and Contact
      Lens Section, were sent a survey of 11 questions pertaining to their astigmatic
      contact lens prescribing habits. Sixty-eight (38%) of those surveyed responded to
      the questionnaire. RESULTS: The results of this survey included the following:
      (1) gas permeable (GP) lenses represented 28.7% of all contact lenses fit; (2) a
      spherical power effect (SPE) bitoric lens was preferred (versus four other
      options) by 58.8% of respondents for a 3.5 diopter (D) refractive astigmat with
      no residual astigmatism, whereas a cylinder power effect (CPE) bitoric was
      preferred by 55.9% for a 3.5 D refractive astigmatic with more than 1 D of
      residual astigmatism; (3) only 10.4% of responding practitioners consider GP
      torics to be difficult to fit. CONCLUSIONS: (1) Back surface toric and bitoric GP
      lenses are considered easy to design and fit by most Diplomates. (2) The Mandell
      Moore guide is the preferred empirical method, and the Polycon SPE is the
      preferred diagnostic fitting method for bitoric lenses for those responding to
      the survey.

PMID- 16458243
TI  - Progressive addition lenses--measurements and ratings.
AB  - BACKGROUND: This study is a followup to a previous study in which the optics of
      several progressive addition lens (PALs) designs were measured and analyzed. The
      objective was to provide information about various PAL designs to enable eye care
      practitioners to select designs based on the particular viewing requirements of
      the patient. METHODS: The optical properties of 12 lenses of the same power for
      each of 23 different PAL designs were measured with a Rotlex Class Plus lens
      analyzer. Lenses were ordered through optical laboratories and specified to be
      plano with a +2.00 diopters add. Measurements were normalized to plano at the
      manufacturer-assigned location for the distance power to eliminate laboratory
      tolerance errors. The magnitude of unwanted astigmatism and the widths and areas
      of the distance, intermediate, and near viewing zones were calculated from the
      measured data according to the same criteria used in a previous study. RESULTS:
      The optical characteristics of the different PAL designs were significantly
      different from one another. The differences were significant in terms of the
      sizes and widths of the viewing zones, the amount of unwanted astigmatism, and
      the minimum fitting height. Ratings of the distance, intermediate, and near
      viewing areas were calculated for each PAL design based on the widths and sizes
      of those zones. Ratings for unwanted astigmatism and recommended minimum fitting
      heights were also determined. Ratings based on combinations of viewing zone
      ratings are also reported. CONCLUSIONS: The ratings are intended to be used to
      select a PAL design that matches the particular visual needs of the patient and
      to evaluate the success and performance of currently worn PALs. Reasoning and
      task analyses suggest that these differences can be used to select a PAL design
      to meet the individual visual needs of the patient; clinical trials studies are
      required to test this hypothesis.

PMID- 16458244
TI  - Relationship between central corneal thickness and severity of glaucomatous
      visual field loss in a primary care population.
AB  - BACKGROUND: Although the ability of central corneal thickness (CCT) to predict
      development of primary open-angle glaucoma has become increasingly well
      recognized, the ability of CCT to predict severity of glaucoma remains uncertain.
      This study was designed to expand the available knowledge about the relationship
      between CCT and glaucoma severity. METHODS: Retrospective identification of all
      patients with a clinical diagnosis of either primary open angle glaucoma (POAG)
      or ocular hypertension who were seen from September 2002 through May 2003 at the
      Albuquerque VA Medical Center eye clinic was completed. Eligible subjects were
      segregated into no, mild, moderate, or advanced visual field loss groups based on
      Advanced Glaucoma Intervention Study (AGIS) visual field scoring criteria.
      Following statistical analyses comparing the visual field groups, the sample was
      divided into thin, intermediate, and thick CCT groups, and further analysis was
      performed. RESULTS: Mean CCT was significantly higher in the no field loss group
      compared with all 3 groups with glaucomatous visual field loss. Mean CCT was not
      statistically different, however, between the mild, moderate, and advanced visual
      field loss groups. In linear regression analyses, no significant relationship was
      found between CCT and severity of visual field loss. CONCLUSIONS: Although CCT
      was associated strongly with development of POAG-related visual field loss, CCT
      was not associated with severity of visual field loss in this study. These
      findings suggest that glaucoma patients with thinner corneas are just as likely
      to have advanced levels of field loss as glaucoma patients with thicker corneas.
      Prospective studies are needed to validate these findings.

PMID- 16458245
TI  - Sometimes a time to be born is also a time to die.

PMID- 16458246
TI  - Part 2: Birth trauma: injuries to the intraabdominal organs, peripheral nerves,
      and skeletal system.
AB  - Part 1 of this 2-part article, "Early Recognition and Treatment of Birth Trauma:
      Injuries to the Head and Face" provided readers with basic concepts related to
      birth trauma to the head and face. Part 2 focuses on the pathophysiology,
      etiology, diagnosis, treatment, and prognosis of birth injuries to the
      intraabdominal organs, the peripheral nerves, the spinal cord, and the skeletal
      system. Risk factors for birth injury to these areas are discussed along with key
      issues related to the nursing care of affected infants.

PMID- 16458247
TI  - Part 1: recognizing neonatal spinal cord injury.
AB  - Neonatal spinal cord injury can occur in utero, as well as after either a
      difficult delivery or a nontraumatic delivery. Spinal cord injury can also be
      related to invasive nursery procedures or underlying neonatal pathology. Early
      clinical signs of spinal cord injury that has occurred in utero or at delivery
      includes severe respiratory compromise and profound hypotonia. Knowledge of risk
      factors and awareness of symptoms is required for early recognition and
      appropriate treatment. This article reviews the embryological development of the
      spinal column highlighting mechanisms of injury and identifying underlying
      factors that increase the risk of spinal cord injury in newborns. Signs and
      symptoms of injury, cervical spine immobilization, and the differential diagnosis
      are discussed. Nursing implications, general prognosis, and research in spinal
      cord injury are provided.

PMID- 16458248
TI  - Origins of tactile vulnerability in high-risk infants.
AB  - PURPOSE: This study examined the degree to which birthweight, gestational age,
      fetal drug exposure, hazardous postnatal medical events, and a mother's
      predisposition toward touch predicted the likelihood of an infant's tactile
      vulnerability during nursing care. SUBJECTS: The convenience sample included 99
      hospitalized infants in their second week of life and their mothers. DESIGN: The
      design was correlational. METHODS: A standardized observational assessment was
      used to code the infant's physiological and behavioral responses to touch during
      4 different episodes of nursing care. Chart review was performed to collect
      information regarding fetal drug exposure, birthweight, gestational age, and
      postnatal medical events. Mothers completed a questionnaire regarding their own
      comfort with using touch and being touched. MEASURES: The Tactile Vulnerability
      Assessment measured infant reactivity to and tolerance for touch during nursing
      care. The Postnatal Complications Scale identified hazardous medical conditions
      and treatments experienced by the infant during the first 2 weeks of life, and
      the Physical Contact Assessment evaluated a mother's predisposition toward touch.
      RESULTS: The number of hazardous postnatal medical events experienced by an
      infant was the primary predictor of tactile vulnerability, accounting for 28% of
      the variance in the infant's likelihood of developing hyperarousal and distress
      from touch during care. Illicit fetal drug exposure and maternal predisposition
      toward touch were also significant predictors. CONCLUSIONS: The significant
      relationship of postnatal medical events to tactile vulnerability suggests that
      it may be associated with the presence of infant pain or injury to the infant's
      central nervous system. Symptoms of drug withdrawal and the impact of teratogens
      on arousal regulation may also be implicated in greater distress from touch by
      infants. In addition, findings suggest the potential for inherited transmission
      of a vulnerability to touch. Assessment of infant vulnerability, including
      discussion with parents about their views of the infant's needs regarding touch,
      may enhance problem identification and early intervention to reduce infant
      distress and further medical problems.

PMID- 16458249
TI  - Implementing a palliative care program in a newborn intensive care unit.
AB  - In the United States the majority of infants who die in the first 27 days end
      their lives in the neonatal intensive care unit (NICU). This article describes
      the implementation of a NICU-based team approach to providing end-of-life care to
      dying infants and their families. Timeline, activities, and resultant
      improvements in family care and staff support are described. Moral distress among
      nurses caring for dying infants is discussed. A case study, neonatal palliative
      care policy, palliative care pathway, and lactation suppression guidelines for
      mothers following infant death are presented. More research is needed to verify
      improvements in neonatal, family, and staff support with palliative care programs
      in the NICU.

PMID- 16458250
TI  - Family teaching toolbox. A parents' guide to palliative care.

PMID- 16458251
TI  - Combined DFT and electrostatics study of the proton pumping mechanism in
      cytochrome c oxidase.
AB  - Cytochrome c oxidase is a redox-driven proton pump which converts atmospheric
      oxygen to water and couples the oxygen reduction reaction to the creation of a
      membrane proton gradient. The structure of the enzyme has been solved; however,
      the mechanism of proton pumping is still poorly understood. Recent calculations
      from this group indicate that one of the histidine ligands of enzyme's CuB
      center, His291, may play the role of the pumping element. In this paper, we
      report on the results of calculations that combined first principles DFT and
      continuum electrostatics to evaluate the energetics of the key energy generating
      step of the model-the transfer of the chemical proton to the binuclear center of
      the enzyme, where the hydroxyl group is converted to water, and the concerted
      expulsion of the proton from delta-nitrogen of His291 ligand of CuB center. We
      show that the energy generated in this step is sufficient to push a proton
      against an electrochemical membrane gradient of about 200 mV. We have also re
      calculated the pKa of His291 for an extended model in which the whole Fe(a3)-CuB
      center with their ligands is treated by DFT. Two different DFT functionals (B3LYP
      and PBE0), and various dielectric models of the protein have been used in an
      attempt to estimate potential errors of the calculations. Although current
      methods of calculations do not allow unambiguous predictions of energetics in
      proteins within few pKa units, as required in this case, the present calculation
      provides further support for the proposed His291 model of CcO pump and makes a
      specific prediction that could be targeted in the experimental test.

PMID- 16458252
TI  - Evaluation of a healthy-weight treatment program for bulimia nervosa: a
      preliminary randomized trial.
AB  - OBJECTIVE: Conduct a randomized treatment trial to test whether healthy dieting
      maintains bulimic symptoms or effectively reduces this eating disturbance.
      METHODS: Female participants (n=85) with full- and sub-threshold bulimia nervosa
      were randomly assigned to a 6-session healthy dieting intervention or waitlist
      condition and assessed through 3-month follow-up. RESULTS: Relative to control
      participants, intervention participants showed modest weight loss during
      treatment and demonstrated significant improvements in bulimic symptoms that
      persisted through follow-up. DISCUSSION: These preliminary results suggest that
      this intervention shows potential for the treatment of bulimia nervosa and may be
      worthy of future refinement and evaluation. Results also provide experimental
      evidence that dieting behaviors do not maintain bulimia nervosa, suggesting the
      need to reconsider maintenance models for this eating disorder.

PMID- 16458253
TI  - Phage display selection of peptides that inhibit metastasis ability of gastric
      cancer cells with high liver-metastatic potential.
AB  - Organ-specific metastasis is an important character of cancer cells. Cancer cells
      that can metastasize to a special organ were thought to have different proteins
      in cell membrane, which might have potential utility as diagnostic markers and
      therapeutic targets. In the present work, based on high liver-metastatic gastric
      cancer cells, XGC9811-L, a screening approach with phage displayed peptide
      library, was successfully used to isolate 8-mer peptide ligands binding to the
      target cells. The phage20 had the highest binding efficiency to XGC9811-L cells,
      which also displayed remarkable cell specificity. Peptide20 that was displayed on
      phage20 could suppress the motility and invasion of XGC9811-L significantly. The
      adhesive ability of XGC9811-L to collagen IV was also inhibited by peptide20.
      Furthermore, phage20 could significantly reduce the incidence of liver metastasis
      of gastric cancer transplanted into nude mice and was also beneficial for the
      reduction the number of metastatic nodules in the liver. In conclusion, the phage
      display is an effective method to screen for the new molecules associated with
      organ-specific metastasis. The selected peptide20 can reverse the liver
      metastasis behavior of the gastric cancer cells.

PMID- 16458255
TI  - Differential gene dosage effects of Ad4BP/SF-1 on target tissue development.
AB  - Ad4BP/SF-1 (NR5A1) was identified as a key regulator of the hypothalamus
      pituitary-gonadal and -adrenal axes. Loss-of-function studies revealed that
      Ad4BP/SF-1 is essential for the development of these tissues and spleen. Here, we
      generated transgenic mouse with BAC recombinants carrying a dual promoter and Tet
      off system. These recombinants have a potential to express lacZ and Ad4BP/SF-1 in
      the tissues where endogenous Ad4BP/SF-1 is expressed. However, protein level of
      Ad4BP/SF-1 varied among the tissues of the transgenic mice and probably thereby
      the target tissues are affected differentially. The BAC-transgenic mice were
      applied to rescue Ad4BP/SF-1 KO mouse. Interestingly, the mice successfully
      rescued the gonad and spleen but failed to rescue the adrenal gland. This
      variation might be dependent on in part the protein expression levels among the
      tissues and in part on differential sensitivities to the gene dosage.

PMID- 16458256
TI  - Exogenous type I collagen facilitates osteogenic differentiation and acts as a
      substrate for mineralization of rat marrow mesenchymal stem cells in vitro.
AB  - We cultured rat mesenchymal stem cells (MSCs) in a medium containing beta
      glycerophosphate, ascorbic acid, and dexamethasone to show in vitro osteogenic
      differentiation of the MSCs. The differentiation was enhanced by adding
      solubilized type I collagen to the medium as evidenced by higher alkaline
      phosphatase activity as well as more calcium deposition than that without
      collagen. The exogenous collagen integrated well with the mineralized bone matrix
      and maintained the native triple helical structure. These findings indicate that
      exogenously supplemented type I collagen acts as a component of the extracellular
      matrix of MSCs, and deposited type I collagen facilitates osteogenic
      differentiation followed by maturation of mineralized bone matrix.

PMID- 16458254
TI  - An ELISA method for the detection and quantification of human heparanase.
AB  - Heparanase is a mammalian endo-beta-D-glucuronidase that cleaves heparan sulfate
      side chains at a limited number of sites. Heparanase enzymatic activity is
      thought to participate in degradation and remodeling of the extracellular matrix
      and to facilitate cell invasion associated with tumor metastasis, angiogenesis,
      and inflammation. Traditionally, heparanase activity was well correlated with the
      metastatic potential of a large number of tumor-derived cell types. More
      recently, heparanase upregulation was detected in an increasing number of primary
      human tumors, correlating, in some cases, with poor postoperative survival and
      increased tumor vascularity. The present study was undertaken to develop a highly
      sensitive ELISA suitable for the determination and quantification of human
      heparanase in tissue extracts and body fluids. The assay preferentially detects
      the 8+50 kDa active heparanase heterodimer vs. the latent 65 kDa proenzyme and
      correlates with immunoblot analysis of heparanase containing samples. It detects
      heparanase at concentrations as low as 200 pg/ml and is suitable for
      quantification of heparanase in tissue extracts and urine.

PMID- 16458257
TI  - Extent of over-expression of hepatocyte growth factor receptor in colorectal
      tumours is dependent on the choice of normaliser.
AB  - For reliable results from quantitative RT-PCR, the starting quantity of total RNA
      and other parameters need to be controlled. Most studies do this by normalising
      their results to a single reference gene. This study quantified the mRNA
      expression of three putative reference genes (ubiquitin C, cyclophilin E, and
      porphobilinogen deaminase) and the target gene hepatocyte growth factor receptor
      (HGFR) in matched colorectal tumour and normal mucosa samples. Each of the
      putative reference genes was found to be significantly over-expressed in the
      tumour samples compared to the normal samples. When HGFR expression was
      normalised to each of these reference genes using the 2 (-DeltaDeltaC(T)) method
      of relative quantification, the number of tumour samples in which HGFR was found
      to be over-expressed varied from 30% to 63% depending on the reference gene
      chosen for normalisation. This shows that normalising to a single reference gene
      without prior validation is inappropriate.

PMID- 16458258
TI  - The effects of cannabinoids on P-glycoprotein transport and expression in
      multidrug resistant cells.
AB  - Cannabis is the most widely used illicit drug in the world. Cannabinoids are used
      therapeutically by some patients as they have analgesic, anti-emetic and appetite
      stimulant properties which palliate adverse symptoms. Use of these agents in an
      oncology setting raises the question of whether they act to modulate the
      effectiveness of concurrently administered anti-cancer drugs. The transporter, P
      glycoprotein (P-gp) confers multiple drug resistance (MDR) by effluxing a diverse
      array of anti-cancer agents. This study was undertaken to examine the effect of
      cannabinoids on P-gp. Unlike the known P-gp inhibitor, PSC833, short 1h exposure
      to three plant-derived cannabinoids, cannabinol (CBN), cannabidiol (CBD) and
      Delta(9)-tetrahydrocannabinol (THC) and the synthetic cannabinoid receptor
      agonist, WIN55, 212-2 (WIN) did not inhibit the efflux of the P-gp substrate
      Rhodamine 123 (Rh123) in either a drug-selected human T lymphoblastoid leukaemia
      cell line (CEM/VLB(100)) or in a mouse fibroblast MDR1 transfected cell line
      (77.1). However, in CEM/VLB(100) cells, prolonged 72 h exposure to the
      cannabinoids, THC and CBD, decreased P-gp expression to a similar extent as the
      flavonoid, curcumin (turmeric). This correlated with an increase in intracellular
      accumulation of Rh123 and enhanced sensitivity of the cells to the cytotoxic
      actions of the P-gp substrate, vinblastine. Taken together, these results provide
      preliminary evidence that cannabinoids do not exacerbate P-gp mediated MDR.
      Further, plant-derived cannabinoids are moderately effective in reversing MDR in
      CEM/VLB(100) cells by decreasing P-gp expression.

PMID- 16458259
TI  - A single administration of testosterone reduces fear-potentiated startle in
      humans.
AB  - BACKGROUND: Ample evidence from animal research indicates that the gonadal
      steroid hormone testosterone has fear-reducing properties. Human data on this
      topic, however, are scarce and far less unequivocal. The present study therefore
      aimed to scrutinize anxiolytic effects of a single dose of testosterone, using a
      direct physiological index of fear in humans. METHODS: Twenty healthy female
      participants were tested in a double-blind, placebo-controlled crossover design
      involving sublingual administration of a single dose of testosterone. Four hours
      after intake, we assessed effects on baseline startle and fear-potentiated
      startle in a verbal threat-of-shock paradigm. RESULTS: In accordance with
      predictions, testosterone administration resulted in reduced fear-potentiated
      startle, without affecting baseline startle. CONCLUSIONS: This study provides
      direct evidence that a single dose of testosterone reduces fear in humans. The
      relationship of this effect to previous research on anxiolytic effects of
      benzodiazepines, as well as possible mechanisms of action, is discussed.

PMID- 16458260
TI  - Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in
      distinct subregions of rat midbrain raphe nucleus: association between gene
      expression and anxiety behavior in the open field.
AB  - BACKGROUND: Ovarian steroids modulate anxiety behavior, perhaps by regulating the
      serotonergic neurons in the midbrain raphe nucleus. The regulation of the brain
      specific isoform of rat tryptophan hydroxylase (TPH2) by ovarian hormones has not
      yet been investigated. Therefore, we examined the effects of estrogen and
      progesterone on TPH2 mRNA in the rat dorsal and median raphe nuclei (DRN and MRN,
      respectively) and whether TPH2 mRNA levels correlated with anxiety behavior.
      METHODS: Ovariectomized rats were treated for two weeks with placebo, estrogen or
      estrogen plus progesterone, exposed to the open field test, and TPH2 mRNA was
      quantified by in situ hybridization histochemistry. RESULTS: Estrogen increased
      TPH2 mRNA in the mid-ventromedial and caudal subregions of the DRN and the caudal
      MRN. Combined estrogen and progesterone treatment did not change TPH2 mRNA
      relative to ovariectomized controls. TPH2 mRNA in caudal DRN was associated with
      lower anxiety-like behavior, whereas TPH2 mRNA in rostral dorsomedial DRN was
      associated with increased anxiety-like behavior. CONCLUSIONS: These results
      suggest that estrogen may increase the capacity for serotonin synthesis in
      discrete subgroups of raphe neurons, and reinforce previous observations that
      different subregions of DRN contribute to distinct components of anxiety
      behavior.

PMID- 16458261
TI  - TNFalpha signaling in depression and anxiety: behavioral consequences of
      individual receptor targeting.
AB  - BACKGROUND: Increased serum levels of TNFalpha and other pro-inflammatory
      cytokines have been found in patients with major depression and several other
      psychiatric conditions. In rodents, these cytokines produce symptoms commonly
      referred to as "sickness behavior." Some of these, including reduced feeding and
      decreased social and exploratory behavior, are reminiscent of those seen in
      depressed patients. Interpretation of these effects is complicated by the malaise
      caused by acute injections of pro-inflammatory cytokines, however. Thus, it is
      unclear whether cytokines are involved in the etiology of depressive symptoms.
      METHODS: We used a panel of behavioral assays to assess TNFR1(-/-) and TNFR2(-/-)
      mice for anxiety and depression-like behaviors. RESULTS: We show that deletion of
      either TNFR1 or TNFR2 leads to an antidepressant-like response in the forced swim
      test and that mice lacking TNFR2 demonstrate a hedonic response in a sucrose
      drinking test compared with wildtype littermates. In addition, deletion of TNFR1
      leads to decreased fear conditioning. There were no differences in behavior in
      anxiety tests for either null mutant. CONCLUSIONS: These results are consistent
      with the hypothesis that TNFalpha can induce depression-like symptoms even in the
      absence of malaise and demonstrate that both receptor subtypes can be involved in
      this response.

PMID- 16458262
TI  - Cortisol circadian rhythm alterations in psychotic major depression.
AB  - BACKGROUND: Increased hypothalamic-pituitary-adrenal axis activity is well
      described in psychotic depression with an emphasis on 24-hour, urinary free
      cortisol levels or dexamethasone suppression tests. There are limited data on
      cortisol levels during specific times of the day. METHODS: Patients with
      depression with (PMD) and without (NPMD) psychosis and healthy control subjects
      were studied using rating scales of depression and psychosis and measures of HPA
      activity, including overnight cortisol and adrenocorticotropin levels. We used
      analysis of variance to determine group differences and regression analyses to
      assess contributions of specific measures to cortisol levels. RESULTS: PMDs had
      higher cortisol during the evening hours than did NPMDs or control subjects, who
      did not differ from one another. Regression analyses suggest that depression and
      the combination of depressive and psychotic symptoms were important contributors
      to variance in evening cortisol. CONCLUSIONS: PMD is associated with increased
      cortisol levels during the quiescent hours. Enhanced cortisol activity,
      particularly a higher nadir, was related to depression severity and the
      interaction of depressive and psychotic symptoms. This increase suggests a defect
      in the action of the circadian timing system and HPA axis, creating a hormonal
      milieu similarly seen in early Cushing's syndrome and potentially an (im)balance
      of mineralocorticoid and glucocorticoid receptor activity.

PMID- 16458263
TI  - Cortical inefficiency in patients with unipolar depression: an event-related FMRI
      study with the Stroop task.
AB  - BACKGROUND: The present study is aimed to examine the neuronal correlates of
      Stroop interference in medication-free patients with major depressive disorder.
      METHODS: Sixteen patients fulfilling Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV) criteria for unipolar depression and 16 healthy control
      subjects matched for age, gender, and education were included. All subjects
      underwent an event-related functional magnetic resonance imaging (fMRI) design
      with an adapted version of the Stroop task including congruent and incongruent
      task conditions. The fMRI experiment was conducted on a 1.5 T magnetic resonance
      (MR) scanner, and item responses were given manually by the subjects. RESULTS:
      With regard to behavioral performance, patients revealed no differences in both
      reaction time and accuracy relative to control subjects. With regard to brain
      activations, direct comparison of patients with control subjects in the
      interference condition revealed hyperactivity in rostral anterior cingulate gyrus
      (rACG) and left dorsolateral prefrontal cortex (DLPFC) in depressive patients,
      which correlated strongly with the Stroop interference. CONCLUSIONS: The study
      provides new evidence for the functioning and dissociation of the anterior
      cingulate in depressed patients. The greater prefrontal activation may reflect a
      cortical inefficiency due to hyperactivity in rACG enhancing the cognitive
      interferences from the emotional state.

PMID- 16458264
TI  - Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental
      modifiers of depression in children.
AB  - BACKGROUND: Child abuse and genotype interact to contribute to risk for
      depression in children. This study examined gene-by-gene and gene-by-environment
      interactions. METHODS: The study included 196 children: 109 maltreated and 87
      nonmaltreated comparison subjects. Measures of psychiatric symptomatology and
      social supports were obtained using standard research instruments, and serotonin
      transporter (5-HTTLPR) (locus SLC6A4) and brain-derived neurotrophic factor
      (BDNF) (variant val66met) genotypes were obtained from saliva-derived DNA
      specimens. Population structure was controlled by means of ancestral proportion
      scores computed based on genotypes of ancestry informative markers in the entire
      sample. RESULTS: There was a significant three-way interaction between BDNF
      genotype, 5-HTTLPR, and maltreatment history in predicting depression. Children
      with the met allele of the BDNF gene and two short alleles of 5-HTTLPR had the
      highest depression scores, but the vulnerability associated with these two
      genotypes was only evident in the maltreated children. A significant four-way
      interaction also emerged, with social supports found to further moderate risk for
      depression. CONCLUSIONS: To the best of our knowledge, this is the first
      investigation to demonstrate a gene-by-gene interaction conveying vulnerability
      to depression. The current data also show a protective effect of social supports
      in ameliorating genetic and environmental risk for psychopathology.

PMID- 16458265
TI  - Microinjection of the L-type calcium channel antagonist diltiazem into the
      ventral nucleus accumbens shell facilitates cocaine-induced conditioned place
      preferences.
AB  - BACKGROUND: Calcium (Ca2+) influx within the nucleus accumbens shell (NASh) can
      influence brain reward processes. We found previously that rats self-administer
      NMDA receptor antagonists (which block Ca2+ influx through NMDA receptors) into
      the NASh. We also found that manipulations which increase expression of Ca2+
      permeable AMPA receptors within this region make cocaine aversive. Here we
      examined if Ca2+ influx via L-type Ca2+ channels within the NASh would influence
      cocaine reward. METHODS: Rats received bilateral microinjections of the L-type
      Ca2+ channel antagonist diltiazem into the ventral NASh prior to place
      conditioning with systemic cocaine. RESULTS: Microinjections of diltiazem (10
      nmol/hemisphere) into the ventral NASh facilitated the ability of a sub-threshold
      dose of cocaine (5.0 mg/kg) to establish place preferences, but did not affect
      place conditioning on their own (5.0-40 nmol/hemisphere). Microinjections into
      more dorsal regions had no effects. CONCLUSIONS: Blockade of Ca2+ influx through
      L-type channels Ca2+ within the ventral NASh increases cocaine reward.

PMID- 16458266
TI  - Blunted HPA axis response to stress influences susceptibility to posttraumatic
      stress response in rats.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with low levels of
      circulating cortisol, and recent studies suggest that cortisol administration may
      reduce PTSD symptoms. This study investigated the role of cortisol in the
      manifestation of anxiety- and fear-like symptoms in an animal model of PTSD.
      METHOD: Magnitude of changes in prevalence of anxiety-like behaviors on the
      elevated plus-maze and nonhabituated exaggerated startle reaction were compared
      in three strains of rats exposed to predator stress, with and without prior
      corticosterone treatment. Extreme behavioral changes in both paradigms implied an
      extreme behavioral response (EBR), representing PTSD-like symptoms. RESULTS:
      Lewis rats exhibited greater baseline anxiety-like behaviors and greater stress
      induced increases in anxiety-like behaviors than Fischer F344 or Sprague-Dawley
      rats, with only minor corticosterone increases following stress. Prevalence of
      EBR was 50% among Lewis rats compared with 10% of Fischer F344 and 25% of Sprague
      Dawley rats. Administering corticosterone 1 hour before stress exposure reduced
      the prevalence of EBR from 50% to 8% in the Lewis rats. CONCLUSIONS: These
      results suggest that a blunted HPA response to stress may play a causal role in
      this model of PTSD and that this susceptibility may be prevented by
      administration of cortisol before stress exposure.

PMID- 16458267
TI  - Basal ganglia-thalamocortical circuitry disruptions in schizophrenia during
      delayed response tasks.
AB  - BACKGROUND: Schizophrenia is characterized by executive functioning deficits,
      presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia
      participants show performance deficits on ocular motor delayed response (ODR)
      tasks, which require both inhibition and spatial working memory for correct
      performance. METHODS: The present functional magnetic resonance imaging (fMRI)
      study compared neural activity of 14 schizophrenia and 14 normal participants
      while they performed ODR tasks. RESULTS: Schizophrenia participants generated: 1)
      more trials with anticipatory saccades (saccades made during the delay period),
      2) memory saccades with longer latencies, and 3) memory saccades of decreased
      accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were
      observed in both groups in ocular motor circuitry (e.g., supplementary eye fields
      [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus,
      and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD
      signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and
      bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations
      between percentage of anticipatory saccade trials and BOLD signal changes were
      more similar between groups for subcortical regions and less similar for cortical
      regions. CONCLUSIONS: These results suggest that executive functioning deficits
      in schizophrenia may be associated with dysfunction of the basal ganglia
      thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal
      ganglia, and thalamus activity in the schizophrenia group during ODR task
      performance.

PMID- 16458268
TI  - Reduced Glucocorticoid Receptor alpha Expression in Mood Disorder Patients and
      First-Degree Relatives.
AB  - BACKGROUND: Individuals with mood disorders exhibit altered function of the
      hypothalamic-pituitary-adrenal (HPA) axis in response to stress. The
      glucocorticoid receptor (GR) plays an important role in the negative feedback
      regulation of the HPA axis. There are two protein isoforms of GR, GRalpha and
      GRbeta, which have distinct biological activity. It has not been examined whether
      GRalpha messenger RNA (mRNA) and GRbeta mRNA expressions are altered in
      peripheral blood cells of mood disorder patients. METHODS: Using quantitative
      reverse transcription polymerase chain reaction (RT-PCR), GRalpha mRNA and GRbeta
      mRNA were measured in peripheral blood cells of major depressive disorder
      patients (depressive n = 18; remissive n = 38), bipolar disorder patients
      (depressive n = 13; remissive n = 35), normal control subjects (n = 31), and
      first-degree relatives of major depressive (n = 17) and bipolar (n = 15) disorder
      patients. RESULTS: Reduced expression of GRalpha mRNA was shown in both bipolar
      and major depressive disorder patients in a current depressive state as well as
      in remission. First-degree relatives of bipolar disorder patients also showed
      GRalpha mRNA reduction. Altered GRbeta mRNA expression was not found in mood
      disorder patients. CONCLUSIONS: Our results suggest that reduced GRalpha mRNA
      expression might be trait-dependent and associated with the pathophysiology of
      mood disorders.

PMID- 16458270
TI  - Immunohistochemical evidence for the localization of neurons containing the
      putative transmitter L-proline in rat brain.
AB  - We examined whether there are the neurotransmitter candidate amino acid L-proline
      containing neurons localized in the rat brain. Antibodies against L-proline
      conjugated with rabbit serum albumin were raised in a rabbit and purified with
      affinity chromatography. Strong L-proline-like immunoreactivity was confined to
      several groups of neurons in the arcuate nucleus (n) and supraoptic n in the
      hypothalamus and area postrema. The brainstem had markedly stained fibers in the
      medial longitudinal fasciculus and localized neuronal cell body labeling in the
      red n, mesencephalic trigeminal n, lateral reticular n, raphe obscurus n,
      solitary n, compact ambiguus n, motor trigeminal n and n of trapezoid body. Our
      findings are consistent with the hypothesis that L-proline may function as a
      neurotransmitter or neuromodulator in the brain.

PMID- 16458269
TI  - Developmental patterns of torsinA and torsinB expression.
AB  - Early onset torsion dystonia is characterized by involuntary movements and
      distorted postures and is usually caused by a 3-bp (GAG) deletion in the DYT1
      (TOR1A) gene. DYT1 codes for torsinA, a member of the AAA+ family of proteins,
      implicated in membrane recycling and chaperone functions. A close relative,
      torsinB may be involved in similar cellular functions. We investigated torsinA
      and torsinB message and protein levels in the developing mouse brain. TorsinA
      expression was highest during prenatal and early postnatal development (until
      postnatal day 14; P14), whereas torsinB expression was highest during late
      postnatal periods (from P14 onwards) and in the adult. In addition, significant
      regional variation in the expression of the two torsins was seen within the
      developing brain. Thus, torsinA expression was highest in the cerebral cortex
      from embryonic day 15 (E15)-E17 and in the striatum from E17-P7, while torsinB
      was highest in the cerebral cortex between P7-P14 and in the striatum from P7
      P30. TorsinA was also highly expressed in the thalamus from P0-P7 and in the
      cerebellum from P7-P14. Although functional significance of the patterns of
      torsinA and B expression in the developing brain remains to be established, our
      findings provide a basis for investigating the role of torsins in specific
      processes such as neurogenesis, neuronal migration, axon/dendrite development,
      and synaptogenesis.

PMID- 16458271
TI  - The role of biological system other than auditory air-conduction in the emergence
      of the hypersonic effect.
AB  - Although human beings cannot perceive elastic vibrations in the frequency range
      above 20 kHz, nonstationary sounds containing a wealth of inaudible high
      frequency components (HFC) above the human audible range activate deep-lying
      brain structures, including the brainstem and thalamus and evoke various
      physiological, psychological, and behavioral responses. In the previous reports,
      we have called these phenomena collectively "the hypersonic effect." It remains
      unclear, however, if vibratory stimuli above the audible range are transduced and
      perceived solely via the conventional air-conducting auditory system or if other
      mechanisms also contribute to mediate transduction and perception. In the present
      study, we have examined the emergence of the hypersonic effect when inaudible HFC
      and audible low-frequency components (LFC) were presented selectively to the
      ears, the entrance of an air-conducting auditory system, or to the body surface
      including the head which might contain some unknown vibratory sensing mechanisms.
      We used two independent measurements based on differing principles; one
      physiological (alpha 2 frequency of spontaneous electroencephalogram [alpha-EEG])
      and the other behavioral (the comfortable listening level [CLL]). Only when the
      listener's entire body surface was exposed to HFC, but not when HFC was presented
      exclusively to the air-conducting auditory system, did both the alpha-EEG and the
      CLL significantly increase compared to the presentation of LFC alone, that is to
      say, there was an evident emergence of the hypersonic effect. The present
      findings suggest that the conventional air-conducting auditory system alone does
      not bring about the hypersonic effect. We may need to consider the possible
      involvement of a biological system distinct from the conventional air-conducting
      auditory nervous system in sensing and transducing high-frequency elastic
      vibration above the human audible range.

PMID- 16458272
TI  - Evidence of reuptake inhibition responsible for mecamylamine-evoked increases in
      extracellular serotonin.
AB  - The present report using microdialysis approach investigates the neurochemical
      mechanism of mecamylamine in the regulation of extracellular serotonin in the
      dorsal raphe nucleus of freely behaving rats. These results suggest that
      mecamylamine may block serotonin reuptake, the effect consistent with its
      efficacy of antidepressant.

PMID- 16458273
TI  - Specific distribution of gabarap, gec1/gabarap Like 1, gate16/gabarap Like 2, lc3
      messenger RNAs in rat brain areas by quantitative real-time PCR.
AB  - GABARAP and GEC1/GABARAPL1 interact with tubulin and GABA(A) receptor and belong
      to a new protein family. This family includes GATE 16 and LC3, potentially
      involved in intracellular transport processes. In this study, we combined brain
      dissection and quantitative real-time reverse transcription polymerase chain
      reaction to study discriminatively gabarap, gec1/gabarapL1, gate16/gabarapL2, lc3
      mRNA distribution in multiple rat brain areas.

PMID- 16458274
TI  - Syntheses of an alpha-D-Gal-(1-->6)-beta-D-Gal diglyceride, as lipase substrate.
AB  - Two different routes were explored to afford 3-O-(6-O-alpha-D-galactopyranosyl
      beta-D-galactopyranosyl)-1,2-di-O-dodecanoyl-sn-glycerol. In the first one, the
      key step was the glycosylation of the 3-O-(2,3,4-tri-O-benzyl-beta-D
      galactopyranosyl)-1,2-O-isopropylidene-sn-glycerol acceptor with 2-pyridyl
      2,3,4,6-tetra-O-benzyl-1-thio-beta-D-galactopyranoside as the donor. In the
      second one, the key step was the coupling of 2,3,4-tri-O-acetyl-6-O-(2,3,4,6
      tetra-O-benzyl-alpha-D-galactopyranosyl)-D-galactopyranosyl trichloroacetimidate
      donor with 1,2-O-isopropylidene-sn-glycerol. Even though the number of steps was
      the same in both pathways, the first one afforded a better overall yield (12.4%)
      than the second one (6.5%). This eight-step synthesis allowed the preparation of
      the expected glycolipid, which was used as substrate for recombinant GPLRP2
      galactolipase using the monomolecular film technique.

PMID- 16458275
TI  - Structural elucidation of the extracellular and cell-wall teichoic acids of
      Staphylococcus aureus MN8m, a biofilm forming strain.
AB  - Extracellular teichoic acid, an essential constituent of the biofilm produced by
      Staphylococcus epidermidis strain RP62A, is also an important constituent of the
      extracellular matrix of another biofilm producing strain, Staphylococcus aureus
      MN8m. The structure of the extracellular and cell wall teichoic acids of the
      latter strain was studied by NMR spectroscopy and capillary electrophoresis-mass
      spectrometry. Both teichoic acids were found to be a mixture of two polymers, a
      (1-->5)-linked poly(ribitol phosphate), substituted at the 4-position of ribitol
      residues with beta-GlcNAc, and a (1-->3)-linked poly(glycerol phosphate),
      partially substituted with the D-Ala at 2-position of glycerol residue. Such
      mixture is unusual for S. aureus.

PMID- 16458276
TI  - Synthesis, characterization, and biological activity of oxovanadium(IV) complexes
      with polyalcohols.
AB  - Oxovanadium(IV) complexes of the polyalcohols sorbitol, galactitol, and mannitol,
      of stoichiometry Na(2)[VO(L)(2)].H(2)O, were obtained from aqueous alkaline
      solutions. They were characterized by elemental analysis, infrared and UV-vis
      spectroscopies, thermoanalytical (thermogravimetric and differential thermal
      analysis) data, and magnetic susceptibility measurements. The biological
      activities of the complexes on the proliferation, differentiation, and glucose
      consumption were tested on osteoblast-like cells (MC3T3E1 osteoblastic mouse
      calvaria-derived cells and UMR106 rat osteosarcoma-derived cells) in culture. The
      three complexes exerted a biphasic effect on cell proliferation, being slight
      stimulating agents at low concentrations and inhibitory in the range of 25-100
      microM. All the complexes inhibited cell differentiation in tumor osteoblasts.
      Their effects on glucose consumption were also discussed. The free ligands did
      not show any effect on the studied biological parameters.

PMID- 16458277
TI  - Synthesis of octa- and dodecamers of D-ribitol-1-phosphate and their protein
      conjugates.
AB  - The bacterial cell-wall-associated teichoic acids contain predominantly D-ribitol
      residues interconnected by phosphodiester linkages. Because of their location,
      these antigens may be vaccine candidates as part of conjugate vaccines. Here, we
      describe the synthesis of extended oligomers of D-ribitol-1-phosphate linked to a
      spacer having an amino group at its terminus. The synthesis utilized a fully
      protected D-ribitol-phosphoramidite that was oligomerized in a stepwise fashion
      followed by deprotection. The free oligomers were connected to bovine serum
      albumin using oxime chemistry. Thus, the ribitol phosphate oligomers were
      converted into keto derivatives, and the albumin counterpart was decorated with
      aminooxy groups. Reaction of the functionalized saccharide and protein moieties
      afforded conjugates having up to 20 ribitol phosphate chains.

PMID- 16458278
TI  - Asymmetric synthesis of methyl 6-deoxy-3-O-methyl-alpha-L-mannopyranoside from a
      non-carbohydrate precursor.
AB  - A novel method is reported for preparing methyl 6-deoxy-3-O-methyl-alpha-L
      mannopyranoside (1) by asymmetric synthesis, using 2-acetylfuran (2), a non
      chiral simple molecule, as the starting material and achieving high yields via
      (S)-1-(2-furyl)ethanol and (S)-1-(2,5-dihydro-2,5-dimethoxy-2-furyl)ethanol.

PMID- 16458279
TI  - Protective effect of the G-765C COX-2 polymorphism on subclinical atherosclerosis
      and inflammatory markers in asymptomatic subjects with cardiovascular risk
      factors.
AB  - BACKGROUND: Cyclooxygenase (COX)-2, a key regulatory enzyme in prostanoid
      synthesis, plays an important role in inflammatory processes. The -765G>C COX-2
      polymorphism has been associated with lower promoter activity in vitro and
      reduced levels of C-reactive protein (CRP) in atherosclerotic carriers of the C
      allele. However, its pathophysiological relevance in vivo has not been fully
      elucidated. METHODS AND RESULTS: We assessed the -765G>C polymorphism and COX-2
      expression in 220 asymptomatic subjects free of cardiovascular disease, in
      relation to global vascular risk, carotid intima-media thickness (IMT), and
      inflammatory markers (fibrinogen, C-reactive protein [CRP], von Willebrand factor
      [vWF] and interleukin-6 [IL-6]). Genotype frequencies were: CC (7.7%), CG
      (34.5%), GG (57.7%). Among hypercholesterolemic subjects (n=140), C allele
      carriers had lower COX-2 expression (p<0.05), reduced carotid IMT (p<0.01) and
      diminished levels of inflammatory markers CRP, vWF and IL-6 (p<0.05), as compared
      to GG homozygous subjects. The association between carotid IMT and COX-2
      polymorphism remained significant after adjusting for cardiovascular risk factors
      and inflammatory markers (p=0.008). CONCLUSIONS: In asymptomatic
      hypercholesterolemic subjects the C allele of -765G>C COX-2 polymorphism was
      associated with lower COX-2 expression, and reduced subclinical atherosclerosis
      and systemic inflammation compared with GG homozygous, thus conferring
      atherosclerosis protection in this cardiovascular risk population.

PMID- 16458280
TI  - Vitamin E protects the insulin sensitivity and redox balance in rat L6 muscle
      cells exposed to oxidative stress.
AB  - BACKGROUND: The effect of reactive oxygen species (ROS) on insulin action is
      unclear. This study was carried out to explore the effect of prolonged low grade
      oxidative stress and vitamin E treatment on cultured rat L6 muscle cells.
      METHODS: L6 myotubes were incubated with vitamin E for 18 h and treated with H2O2
      generating system for 12 h. Insulin stimulated glucose uptake, total antioxidant
      capacity and reduced glutathione concentration were measured. RESULTS: There was
      a marked decrease in insulin stimulated glucose transport in L6 cells exposed to
      H2O2 generating system. Pretreatment with vitamin E attenuates the effect of H2O2
      on insulin action. Treatment with H2O2 caused a significant reduction in the
      levels of reduced glutathione and total antioxidant capacity, these alterations
      were reversed by vitamin E pretreatment. Vitamin E per se had no effect on
      insulin stimulated glucose transport in cells not exposed to oxidative stress.
      CONCLUSION: In conclusion, our observations indicate that vitamin E improves the
      free radical defense system potential and prevents oxidative stress induced
      insulin resistance in rat L6 muscle cells.

PMID- 16458281
TI  - Lisinopril ameliorates paraquat-induced lung fibrosis.
AB  - BACKGROUND: Paraquat is a controversial and one of the most commonly used
      herbicides in the world. Although liver, kidney, heart and CNS are affected, lung
      damage resulting to pulmonary fibrosis is the usual cause of deaths in the cases
      with intoxication. The mechanism of paraquat toxicity is not clear but probably
      includes the induction of lipid peroxidation of unsaturated fatty acids.
      Lisinopril, an angiotensin-converting enzyme inhibitor (ACEI), an
      antihypertensive drug, has beneficial effects on the treatment of fibrosis. The
      antifibrotic effect of lisinopril has shown to be due to inhibition of synthesis
      of angiotensin II that causes stimulation of fibroblast proliferation and
      collagen synthesis. METHOD: Male albino Wistar rats were used in the experiments
      (weighing 150-300 g). The animals were divided into 5 groups: group I received
      saline, group II received lisinopril (1 mg/kg; po), group III was given a single
      i.p. dose of 20 mg/kg paraquat, group IV (treatment group) received lisinopril
      after single a i.p. dose of 20 mg/kg paraquat, and group V (pre-treatment group)
      received lisinopril before a single i.p. dose of 20 mg/kg paraquat. After 21 days
      of treatment, the level of hydroxyproline and the degree of lipid peroxidation
      were determined in the lung tissue of the animals and the lungs were examined
      histologically for fibrosis. RESULT: Paraquat caused a significant increase in
      hydroxyproline content and lisinopril significantly decreased the amount
      hydroxyproline (p<0.001) in the lung tissue of the rats. The histological
      examination also indicated that lisinopril can effectively protect the paraquat
      induced lung fibrosis. The lipid peroxidation levels in the lung were not
      significantly changed when compared to the control group. CONCLUSION: The
      antifibrotic effect of lisinopril may be due to inhibition of angiotensin II or
      proline moiety, which is a common structural in all ACEI, drugs.

PMID- 16458282
TI  - Isolation of highly purified DNA from low-abundance archived and stained
      cytological specimens.

PMID- 16458283
TI  - Allele-specific detection of C-1562T polymorphism in the matrix metalloproteinase
      9 gene: genotyping by MADGE.
AB  - OBJECTIVES: The aim was to design a method for genotyping MMP-9 C-1562T gene
      polymorphism that does not require RFLP PCR or sequencing. DESIGN AND METHODS:
      Optimization of tetra-primer ARMS PCR was performed to obtain the highest amount
      of specific amplification products. RESULTS: PCR products (436 bp, 296 bp, 220
      bp) were visualized on MADGE or agarose gel electrophoresis. CONCLUSIONS: We
      designed a faster, single-step, economical method which becomes advantageous for
      high throughput population screening.

PMID- 16458285
TI  - Zfh1, a somatic motor neuron transcription factor, regulates axon exit from the
      CNS.
AB  - Motor neurons are defined by their axon projections, which exit the CNS to
      innervate somatic or visceral musculature, yet remarkably little is known about
      how motor axons are programmed to exit the CNS. Here, we describe the role of the
      Drosophila Zfh1 transcription factor in promoting axon exit from the CNS. Zfh1 is
      detected in all embryonic somatic motor neurons, glia associated with the CNS
      surface and motor axons, and one identified interneuron. In zfh1 mutants, ventral
      projecting motor axons often stall at the edge of the CNS, failing to enter the
      muscle field, despite having normal motor neuron identity. Conversely, ectopic
      Zfh1 induces a subset of interneurons--all normally expressing two or more
      "ventral motor neuron transcription factors" (e.g. Islet, Hb9, Nkx6, Lim3)--to
      project laterally and exit the CNS. We conclude that Zfh1 is required for ventral
      motor axon exit from the CNS.

PMID- 16458284
TI  - LeX is expressed by principle progenitor cells in the embryonic nervous system,
      is secreted into their environment and binds Wnt-1.
AB  - LeX/SSEA1/CD15 is an extracellular matrix-associated carbohydrate expressed by ES
      cells and by adult neural and bone marrow stem cells. It is important for cell
      adhesion, compaction and FGF2 responses of early embryonic stem cells; however,
      its function at later stages is not clear. We now show that LeX is expressed by
      primary mouse neural progenitor cells, including neural stem cells, neuroblasts
      and glioblasts, but not by their more differentiated products. LeX distinguishes
      highly proliferative cells even in the primitive neuroepithelium, demonstrating
      heterogeneity in cell potential before radial glia arise. At later stages, LeX
      expressing progenitors are frequently radial in morphology. Surface LeX
      expression can be used to enrich neural stem and progenitor cells from different
      CNS regions throughout development by FACS. We found that LeX expression is
      particularly strong in neural regions with prolonged neurogenesis, e.g., the
      olfactory epithelium, hippocampus, basal forebrain and cerebellum. These regions
      also express high levels of the growth factors FGF8 and/or Wnt-1. We show here
      that LeX-containing molecules in the developing nervous system bind Wnt-1. Our
      findings suggest that LeX, which is present on the surface of principle neural
      progenitors and secreted into their extracellular niche, may bind and present
      growth factors important for their proliferation and self-renewal.

PMID- 16458286
TI  - Menarche in women with high exposure to persistent organochlorine pollutants in
      utero and during childhood.
AB  - In animal studies, exposure to persistent organochlorine pollutants (POPs) in
      utero and through mother's milk has been suggested to affect the onset of
      puberty. However, human studies are scarce and ambiguous. In the present study,
      information on age at menarche was collected from 545 women who had been brought
      up in a fishing village/family on the Swedish east coast, off the Baltic Sea, and
      therefore were assumed to have been exposed to POPs in utero, through breast
      feeding, and/or through dietary habits during their childhood. The average age at
      menarche for these women was compared to that of three referent groups: (a) 1252
      women who also had been brought up in a fishing village/family, but on the
      Swedish west coast, where the fish had been considerably less contaminated; (b)
      634 women from the east coast, but who had not grown up in a fishing
      village/family; and (c) 869 women from the west coast who had not grown up in a
      fishing village/family. Based on previous studies, all groups were regarded as
      having similar socioeconomic circumstances. Data were analyzed using analysis of
      variance (ANOVA). In an attempt to account for variations in environmental
      concentrations of POPs over time, all analyses were adjusted for year of birth.
      Exposed women were found to be slightly older at menarche than referent women
      from the same coastal area (mean age 13.0 vs 12.8 yr). No differences were found
      between the exposed women and the two other referent groups (mean age 13.0 yr in
      all groups).

PMID- 16458288
TI  - Control by cholinergic mechanisms.
AB  - In the respiratory tract acetylcholine is neurotransmitter in ganglia and
      postganglionic parasympathetic nerves, but in addition is paracrine mediator
      released from various non-neuronal cells. Almost every cell type present in the
      respiratory tract expresses nicotinic and muscarinic receptors and therefore
      appears to be a target for acetylcholine. The present review describes the
      mechanisms of synthesis and release of acetylcholine from neuronal and non
      neuronal cells and the differential control mechanisms. The different
      cholinoceptors, multiple nicotinic and muscarinic receptors and their signalling
      are outlined and their involvement in the modulation of the function of various
      target cells, smooth muscles, nerves, surface epithelial, secretory cells,
      fibroblasts and inflammatory cells is discussed in detail.

PMID- 16458287
TI  - Arsenic speciation transported through the placenta from mother mice to their
      newborn pups.
AB  - The primary goal of the present study was to confirm the arsenic species that can
      be transferred from the mother to the bodies of newborn pups through the placenta
      and the speciated arsenic distribution in the liver and brain of newborn mice
      after gestational maternal exposure to inorganic arsenic (iAs). Mother mice were
      exposed to iAsIII and iAsV in drinking water during gestation. The livers and
      brains of the mother mice and their newborn pups were taken. Contents of iAs,
      monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic
      (TMA) compound were detected using the HG-AAS method. Contents of iAs, MMA, and
      DMA in the liver of mother mice increased with the concentration of arsenite or
      arsenate in their drinking water. However, only DMA increased with the
      concentration of arsenate or arsenite in the drinking water in the brain of
      mother mice. On the other hand, contents of both iAs and DMA in the liver and
      brain of newborn mice increased with the concentration of arsenate or arsenite
      administered to their mother orally. Contents of arsenic species in the liver and
      brain of both mother mice and their newborn pups were significantly lower in the
      10 ppm iAsV group than in the 10 ppm iAsIII group. Ratios of iAs or DMA levels
      between the brain and the liver of newborn mice were larger than 1, whereas those
      in mother mice were much smaller than 1. iAs taken from drinking water was
      distributed and metabolized mainly in the liver of mother mice. iAsIII in low
      levels may be taken up and metabolized easily in the liver compared to iAsV. Both
      iAs and DMA are transferred from the mother through the placenta and cross the
      immature blood-brain barrier (BBB) easily. Compared to that in the liver of
      newborn mice, DMA as an organic metabolite is prevalent in brain, a lipidic
      organ, if the BBB is not matured enough to prevent it from entering the brain.

PMID- 16458289
TI  - Phosphodiesterase inhibitors in airways disease.
AB  - Phosphodiesterases hydrolyse intracellular cyclic nucleotides, cyclic adenosine
      monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) into inactive 5'
      monophosphates, and exist as 11 families. They are found in a variety of
      inflammatory and structural cells. Inhibitors of PDEs allow the elevation of cAMP
      and cGMP which lead to a variety of cellular effects including airway smooth
      muscle relaxation and inhibition of cellular inflammation or of immune responses.
      PDE4 inhibitors specifically prevent the hydrolysis of cAMP, and PDE4 isozymes
      are present in inflammatory cells. Selective PDE4 inhibitors have broad spectrum
      anti-inflammatory effects such as inhibition of cell trafficking, cytokine and
      chemokine release from inflammatory cells, such as neutrophils, eosinophils,
      macrophages and T cells. The second generation PDE4 inhibitors, cilomilast and
      roflumilast, have reached clinical trial stage and have some demonstrable
      beneficial effects in asthma and chronic obstructive pulmonary disease (COPD).
      The effectiveness of these PDE4 inhibitors may be limited by their clinical
      potency using doses that have minimal effects on nausea and vomiting. Topical
      administration of PDE4 inhibitors may provide a wider effective to side-effect
      profile. Development of inhibitors of other PDE classes, combined with PDE4
      inhibition, may be another way forward. PDE5 is an inactivator of cGMP and may
      have beneficial effects on hypoxic pulmonary hypertension and vascular
      remodelling. PDE3 and PDE7 are other cAMP specific inactivators of cAMP. PDE7 is
      involved in T cell activation and a dual PDE4-PDE7 inhibitor may be more
      effective in asthma and COPD. A dual PDE3-PDE4 compound may provide more
      bronchodilator and bronchoprotective effect in addition to the beneficial PDE4
      effects.

PMID- 16458290
TI  - Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic
      airway inflammation.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      activated transcription factor belonging to the nuclear hormone receptor
      superfamily. PPARgamma regulates several metabolic pathways by binding to
      sequence-specific PPAR response elements in the promoter region of target genes,
      including lipid biosynthesis and glucose metabolism. Synthetic PPARgamma agonists
      have been developed, such as the thiazolidinediones rosiglitazone and
      pioglitazone. These act as insulin sensitizers and are used in the treatment of
      type 2 diabetes. Recently however, PPARgamma ligands have been implicated as
      regulators of cellular inflammatory and immune responses. They are thought to
      exert anti-inflammatory effects by negatively regulating the expression of pro
      inflammatory genes. Several studies have demonstrated that PPARgamma ligands
      possess anti-inflammatory properties and that these properties may prove helpful
      in the treatment of inflammatory diseases of the airways. This review will
      outline the anti-inflammatory effects of synthetic and endogenous PPARgamma
      ligands and discuss their potential therapeutic effects in animal models of
      inflammatory airway disease.

PMID- 16458291
TI  - The arginine-arginase balance in asthma and lung inflammation.
AB  - Asthma, a complex chronic inflammatory pulmonary disorder, is on the rise despite
      intense ongoing research underscoring the need for new scientific inquiry. Using
      global microarray analysis, we have recently uncovered that asthmatic responses
      involve metabolism of arginine by arginase. We found that the cationic amino acid
      transporter (CAT)2, arginase I, and arginase II were particularly prominent among
      the allergen-induced gene transcripts. These genes are key regulators of critical
      processes associated with asthma including airway tone, cell hyperplasia and
      collagen deposition, respectively. Furthermore, systemic arginine levels and
      arginine metabolism via nitric oxide synthase (NOS) can have profound effect on
      lung inflammation. This review focuses on the current body of knowledge on l
      arginine metabolism in asthma and lung inflammation.

PMID- 16458292
TI  - Nerve growth factor: the central hub in the development of allergic asthma?
AB  - Neurotrophins like nerve growth factor (NGF), originally described as nerve
      growth factors in neuronal development, have been implicated in many
      physiological processes in the last years. They are now regarded as important
      factors involved in the resolution of pathological conditions. NGF has profound
      effects on inflammation, repair and remodeling of tissues. However, in the lung
      these beneficial effects can transact into disease promoting actions, e.g., in
      allergic inflammation or respiratory syncytial virus (RSV) infection.
      Overproduction of NGF then enhances inflammation, and promotes (neuronal) airway
      hyperreactivity and neurogenic inflammation. We hypothesize that NGF
      overexpression in certain vulnerable time windows during infancy could be a major
      risk factor for the development of asthma symptoms.

PMID- 16458293
TI  - Prostanoids as pharmacological targets in COPD and asthma.
AB  - COPD (Chronic Obstructive Pulmonary Disease) and bronchial asthma are two severe
      lung diseases which represent a major problem of world public health.
      Leukotrienes and prostanoids play an important role in the pathogenesis of
      pulmonary diseases. Prostanoids: prostaglandins (PGs) and thromboxane A2 (TXA2),
      the cyclooxygenase metabolites of arachidonic acid are implicated in the
      inflammatory cascade that occurs in asthmatic airways. Recently, the roles played
      by isoprostanes or prostaglandin-like compounds nonenzymatically generated via
      peroxidation of membrane phospholipids by reactive oxygen species, in particular
      F2-isoprostanes, in pulmonary pathophysiology have been highlighted. This article
      aims to provide an overview of the role of prostanoids and isoprostanes in the
      pathogenesis of COPD and asthma and to discuss the pharmacological strategies
      developed in prevention and/or treatment of these pathologies.

PMID- 16458294
TI  - Entamoeba histolytica: comparison of the role of receptors and filamentous actin
      among various endocytic processes.
AB  - Entamoeba histolytica is the causative agent of amoebic dysentery. Uptake of iron
      is critical for E. histolytica growth and iron-bound human transferrin (holo
      transferrin) has been shown to serve as an iron source in vitro. Although a
      transferrin-binding protein has been identified in E. histolytica, the mechanism
      by which this iron source is taken up by this pathogen is not well understood. To
      gain insight into this process, the uptake of fluorescent-dextran, -holo
      transferrin, and human red blood cells (hRBCs) was compared. Both dextran and
      transferrin were taken up in an apparent receptor-independent fashion as compared
      to hRBCs, which were taken up in a receptor-mediated fashion. Interestingly, the
      uptake of FITC-dextran and FITC-holo-transferrin differentially relied on an
      intact actin cytoskeleton suggesting that their internalization routes may be
      regulated independently.

PMID- 16458295
TI  - Echinococcus multilocularis: developmental stage-specific expression of Antigen B
      8-kDa-subunits.
AB  - Antigen B (AgB) initially found in hydatid cyst fluid of Echinococcus granulosus
      is a polymeric lipoprotein of 160 kDa, and is an aggregate of several different
      but homologous small proteins with approximately 8 kDa. Four genes encoding these
      8-kDa-subunits have been identified from E. granulosus. In this study we isolated
      five genes encoding 8-kDa-subunits of AgB from Echinococcus multilocularis.
      Sequence comparison of isolated cDNA clones demonstrated that one of these five
      clones was completely identical to EmAgB8/1 which had been isolated previously by
      our group, and three of them were 94.5, 90.8, and 91.9% homologous to E.
      granulosus antigen B 8-kDa subunit genes, EgAgB8/2, EgAgB8/3, and EgAgB8/4,
      respectively. The remaining clone shared 51-58% homology with the nucleotide
      sequences of AgB genes. Gene-specific RT-PCR and Western blot analyses revealed
      that these genes were expressed in a developmentally regulated manner in E.
      multilocularis vesicles, protoscoleces, and immature adult worms. Possible
      functions of different expression manners are also discussed.

PMID- 16458296
TI  - Schistosoma mansoni: use of a fluorescent indicator to detect nitric oxide and
      related species in living parasites.
AB  - Nitric oxide (NO) is synthesized enzymatically by nitric oxide synthase (NOS).
      Several groups have previously presented evidence for NOS activity and
      immunoreactivity in several parasitic platyhelminths, including schistosomes.
      Here, we use 4,5-diaminofluorescein-2 diacetate (DAF-2 DA), a fluorescent
      indicator of NO, to detect NO in living schistosomes. In adult worms, DAF-2
      fluorescence is found selectively in epithelial-like cells. Fluorescence
      increases when worms are incubated in L-arginine, the precursor of NO synthesis,
      and decreases dramatically in the presence of the NOS inhibitor N(G)-nitro-L
      arginine methyl ester, indicating that predicted NO release may be NOS-dependent,
      and that enzymatic NO signaling pathways may play an important role in
      schistosome physiology.

PMID- 16458297
TI  - Isolation and characterization of another cDNA encoding a chorismate mutase from
      the phytoparasitic nematode Meloidogyne arenaria.
AB  - A new cDNA, named Ma-cm-2, encoding a chorismate mutase (CM), has been isolated
      from Meloidogyne arenaria. The full-length cDNA, carrying the trans-spliced SL1
      leader sequence, was 753-bp long with an open reading frame of 576 bp. The
      deduced protein MA-CM-2 including amino-terminal signal peptide shows significant
      similarity to CMs of Meloidogyne incognita, Meloidogyne javanica, and also
      bacteria. Secondary structure prediction of MA-CM-2 indicates the presence of the
      three conserved alpha-helix domains present in the Escherichia coli CMs. Reverse
      transcription and polymerase chain reaction analysis showed that its transcript
      abundance is high in the early developmental stages and low in later ones. In
      situ mRNA hybridization revealed that the transcripts of Ma-cm-2 accumulated
      specifically in the two subventral oesophageal gland cells of M. arenaria. The
      widespread existence of CMs in the sedentary endoparasitic nematodes implicates
      that this enzyme plays an important role in the host-parasite interaction.

PMID- 16458298
TI  - Toxoplasma gondii: expression pattern and detection of infection using full
      length recombinant P35 antigen.
AB  - A complete P35 surface antigen of Toxoplasma gondii was sequenced (GenBank ).
      Immunoblot found that it reacted specially with T. gondii acute infected sera,
      and the recombinant P35 signal was specific for P35 antigen. The P35-GST protein
      was used as antigen to detect 125 sera samples by double-sandwich ELISA. P35-IgM
      positive rate in a chronic infected group, a persistent IgM positive chronic
      group, a recently seroconvered group and an acute infected group were 4% (1 out
      of 25), 16% (4 out of 25), 88% (22 out of 25), and 100% (25 out of 25),
      respectively. The sensitivity and specificity of the recombinant full-length P35
      antigen were 100 and 96%, respectively. The detailed expression patterns of P35
      antigen were studied in 36 IgM and IgG positive sequential samples from 10
      recently seroconvered patients. Results showed that the P35-IgM positive rate
      decreased as the time after the first seroconversion increased. P35-IgM positive
      samples in the first, second, third, fourth, and fifth month after the first
      seroconversion test were 90, 78, 57, 50, and 33%, respectively. P35-IgG positive
      samples in the first, second, third, fourth, fifth, sixth, and seventh month
      after the first seroconversion test were 70, 100, 100, 100, 67, 100, and 100%,
      respectively. All samples were P35-IgM negative after the fifth month, and P35
      IgG negative after the seventh month from seroconversion. P35-IgM existed the
      shortest time and was a more specific marker for T. gondii acute infection than
      P35-IgG, IgM, and IgG to whole tachyzoites antigens.

PMID- 16458299
TI  - Toxoplasma gondii: comparison of a rhoptry-ELISA with IFAT and MAT for antibody
      detection in sera of experimentally infected pigs.
AB  - Indirect ELISA and IFAT have been reported to be more sensitive and specific than
      agglutination tests. However, MAT is cheaper, easier than the others and does not
      need special equipment. The purpose of this study was to compare an enzyme linked
      immunosorbent assay using crude rhoptries of Toxoplasma gondii as coating wells
      (r-ELISA) with indirect fluorescence antibody test (IFAT) and modified
      agglutination test (MAT) to detect anti-T. gondii antibodies in sera of
      experimentally infected pigs. Ten mixed breed pigs between 6.5 and 7.5 weeks old
      were used. All pigs were negative for the presence of T. gondii antibodies by
      IFAT (titre < 16), r-ELISA (OD < 0.295) and MAT (titre < 16). Animals received
      7x10(7) viable tachyzoites of the RH strain by intramuscular (IM) route at day 0.
      Serum samples were collected at days -6, 0, 7, 14, 21, 28, 35, 42, 50, and 57.
      IFAT detected anti-T. gondii antibodies earlier than r-ELISA and MAT. The average
      of antibody levels was higher at day 35 in IFAT (Log10=2.9) and in MAT (Log10 =
      3.5), and at day 42 in r-ELISA (OD = 0.797). The antibody levels remained high
      through the 57th day after inoculation in MAT, and there was a decrease tendency
      in r-ELISA and IFAT. IFAT was used as "gold standard" and r-ELISA demonstrated a
      higher prevalence (73.3%), sensitivity (94.3%), negative predictive value
      (83.3%), and accuracy (95.6%) than MAT. Kappa agreements among tests were
      calculated, and the best results were shown by r-ELISAxIFAT (kappa = 0.88, p <
      0.001). Cross-reaction with Sarcocystis miescheriana was investigated in r-ELISA
      and OD mean was 0.163 +/- 0.035 (n = 65). Additionally, none of the animals
      inoculated with Sarcocystis reacted positively in r-ELISA. Our results indicate
      that r-ELISA could be a good method for serological detection of T. gondii
      infection in pigs.

PMID- 16458300
TI  - Toxoplasma gondii: in vitro and in vivo activities of the hydroxynaphthoquinone 2
      hydroxy-3-(1'-propen-3-phenyl)-1,4-naphthoquinone alone or combined with
      sulfadiazine.
AB  - The compound 2-hydroxy-3-(1'-propen-3-phenyl)-1,4-naphthoquinone (PHNQ6) was
      evaluated for activity against Toxoplasma gondii, alone or combined with
      sulfadiazine. Treatment with PHNQ6 combined with sulfadiazine protected at least
      70 and 90% of mice infected with RH and EGS strains, respectively. Mice were
      treated with PHNQ6 (50 mg/kg/day) alone or combined with sulfadiazine (40 mg/L)
      30 days after infection with P strain. The number of brain cysts was lower in
      mice treated with PHNQ6 alone or combined with sulfadiazine compared to that in
      control mice. Degenerated bradyzoites were observed in animals treated with
      PHNQ6. Infectivity of bradyzoites treated with PHNQ6 alone or combined with
      sulfadiazine was inhibited after in vitro incubation.

PMID- 16458301
TI  - Plasmodium vivax: in vitro susceptibility of blood stages to synthetic trioxolane
      compounds and the diamidine DB75.
AB  - Plasmodium vivax is an important human pathogen causing malaria in more temperate
      climates of the world. Similar to Plasmodium falciparum, the causative agent for
      malaria tropica, drug resistance is beginning to emerge for this parasite species
      and this hampers adequate treatment of infection. We have used a short-term ex
      vivo drug assay to monitor activity of OZ277 (RBx-11160), a fully synthetic anti
      malarial peroxide, and the diamidine DB75 against P. vivax. For both compounds as
      well as the anti-malarial reference compounds artesunate, artemether, and
      chloroquine, the in vitro IC(50) values were determined in one-cycle hypoxanthine
      incorporation assays. Results from such assays were found to be very similar
      compared to IC(50) values obtained from one-cycle P. falciparum hypoxanthine
      assays. We demonstrate the anti-parasite activity of OZ277 and the reference
      compounds to be faster than that of DB75. These data warrant clinical testing of
      OZ277 against P. vivax malaria and support recent data on clinical activity
      against P. vivax for DB75.

PMID- 16458302
TI  - The muO-conotoxin MrVIA inhibits voltage-gated sodium channels by associating
      with domain-3.
AB  - Several families of peptide toxins from cone snails affect voltage-gated sodium
      (Na(V)) channels: mu-conotoxins block the pore, delta-conotoxins inhibit channel
      inactivation, and muO-conotoxins inhibit Na(V) channels by an unknown mechanism.
      The only currently known muO-conotoxins MrVIA and MrVIB from Conus marmoreus were
      applied to cloned rat skeletal muscle (Na(V)1.4) and brain (Na(V)1.2) sodium
      channels in mammalian cells. A systematic domain-swapping strategy identified the
      C-terminal pore loop of domain-3 as the major determinant for Na(V)1.4 being more
      potently blocked than Na(V)1.2 channels. muO-conotoxins therefore show an
      interaction pattern with Na(V) channels that is clearly different from the
      related mu- and delta-conotoxins, indicative of a distinct molecular mechanism of
      channel inhibition.

PMID- 16458303
TI  - The regulation of Bax by c-Jun N-terminal protein kinase (JNK) is a prerequisite
      to the mitochondrial-induced apoptotic pathway.
AB  - The signaling mechanism by which JNK affects mitochondria is critical to initiate
      apoptosis. Here we show that the absence of JNK provides a partial resistance to
      the toxic effect of the heavy metal cadmium. Both wild type and jnk-/-
      fibroblasts undergoing death exhibit cytosolic cytochrome c but, unlike wild type
      cells, the JNK-deficient fibroblasts do not display increased caspase activity
      and DNA fragmentation. The absence of apoptotic death correlates with a specific
      defect in activation of Bax. We conclude that JNK-dependent regulation of Bax is
      essential to mediate the apoptotic release of cytochrome c regardless of Bid and
      Bim activation.

PMID- 16458304
TI  - Glyceraldehyde dehydrogenases from the thermoacidophilic euryarchaeota
      Picrophilus torridus and Thermoplasma acidophilum, key enzymes of the non
      phosphorylative Entner-Doudoroff pathway, constitute a novel enzyme family within
      the aldehyde dehydrogenase superfamily.
AB  - Cells of Picrophilus torridus, grown on glucose, contained all enzyme activities
      of a non-phosphorylative Entner-Doudoroff pathway, including glucose
      dehydrogenase, gluconate dehydratase, 2-keto-3-deoxygluconate aldolase,
      glyceraldehyde dehydrogenase (GADH), glycerate kinase (2-phosphoglycerate
      forming), enolase and pyruvate kinase. GADH was purified to homogeneity. The 115
      kDa homodimeric protein catalyzed the oxidation of glyceraldehyde with NADP+ at
      highest catalytic efficiency. NAD+ was not used. By MALDI-TOF analysis, open
      reading frame (ORF) Pto0332 was identified in the genome of P. torridus as the
      encoding gene, designated gadh, and the recombinant GADH was characterized. In
      Thermoplasma acidophilum ORF Ta0809 represents a gadh homolog with highest
      sequence identity; the gene was expressed and the recombinant protein was
      characterized as functional GADH with properties very similar to the P. torridus
      enzyme. Sequence comparison and phylogenetic analysis define both GADHs as
      members of novel enzyme family within the aldehyde dehydrogenase superfamily.

PMID- 16458306
TI  - Discovering differential activation machinery of the Toll-like receptor 4
      signaling pathways in MyD88 knockouts.
AB  - To understand differential time activation of nuclear factor kappaB (NF-kappaB)
      and the temporal features of the downstream pro-inflammatory cytokines' [tumour
      necrosis-factor-alpha (TNF-alpha) and IP-10] mRNA levels in myeloid
      differentiation primary-response protein 88 (MyD88) knockouts (KOs), I developed
      a computational model of the TLR4 pathway. The result suggests that the late
      phase expression of NF-kappaB activity observed in MyD88 KOs is possibly due to a
      number of novel intermediates acting along the MyD88-independent pathway. I also
      simulate that the TNF-alpha levels will increase at a longer time in MyD88 KOs,
      not previously mentioned.

PMID- 16458305
TI  - Clusters of PE and PPE genes of Mycobacterium tuberculosis are organized in
      operons: evidence that PE Rv2431c is co-transcribed with PPE Rv2430c and their
      gene products interact with each other.
AB  - About 10% of the coding capacity of the Mycobacterium tuberculosis (M. tb) genome
      is devoted to the PE/PPE family of genes scattered throughout the genome. We have
      identified 28 PE/PPE operons which are organized within the M. tb genome in such
      a way that most PE members are upstream to PPE members. One example of such a
      gene arrangement is the PPE gene Rv2430c, earlier shown by us to code for a
      highly antigenic protein eliciting strong B-cell responses in TB patients
      [Choudhary, R.K., Mukhopadhyay, S., Chakhaiyar, P., Sharma, N., Murthy, K.J.R.,
      Katoch V.M. and Hasnain, S.E. (2003) PPE antigen Rv2430c of Mycobacterium
      tuberculosis induces a strong B cell response. Infect. Immun. 71, 6338-6343],
      situated downstream to PE gene Rv2431c. Rv2431c and Rv2430c are transcribed as an
      operon. Expression of either rRv2431c or rRv2430c alone in E. coli limited their
      localization to the inclusion bodies. However, when they were co-expressed, both
      the proteins appeared in the soluble fraction. These two proteins interact with
      each other and form oligomers when alone, however, when present together they
      exist as heteromer.

PMID- 16458307
TI  - Mapping nucleolar localization sequences of 1A6/DRIM.
AB  - Human 1A6/downregulated in metastasis (DRIM) is a nucleolar protein with multiple
      HEAT-repeat motifs (Huntington, elongation factor 3, a subunit of protein
      phosphatase 2A, target of rapamycin). The yeast homologue to 1A6/DRIM, Utp20, is
      part of the small subunit processome and functions in 18S RNA processing. In the
      present study, we utilized the green fluorescent protein as the fusion protein
      marker to investigate the sequence responsible for 1A6/DRIM accumulation in
      nucleolus. Deletion sequence analysis demonstrated that a single region located
      between amino acids 2744 and 2761 at the C-terminus of 1A6/DRIM is capable of
      nucleolar accumulation. Two basic amino acid clusters within this region are
      essential for nucleolar accumulation. The sequences required for nucleolar
      accumulation overlaps the putative nuclear localization signal of 1A6/DRIM.

PMID- 16458308
TI  - Multidrug resistance associated protein 1 protects against bilirubin-induced
      cytotoxicity.
AB  - We have shown that multidrug resistance associated protein 1 (MRP1) mediates ATP
      dependent extrusion of bilirubin, possibly limiting its potentially toxic
      accumulation in cells. To determine directly if Mrp1 protects cells against
      unconjugated bilirubin (UCB) toxicity, mouse embryo fibroblasts (MEF) were
      isolated from Mrp1 knockout (-/-) mice and their wild type (WT) (+/+)
      littermates. Compared to WT cells, cultured MEF (-/-) cells exposed to 40-140 nM
      unbound [H3]-bilirubin accumulated twice as much [H3]-bilirubin (P<0.01). This
      was associated with greater, dose-related cytotoxicity, assessed by the
      methylthiazoletetrazolium test, lactate dehydrogenase release and cellular ATP
      content. The data confirm that Mrp1 limits intracellular accumulation of UCB and
      thus decreases its cytotoxicity.

PMID- 16458309
TI  - Effects of bilateral and unilateral ophthalmectomy on plasma melatonin in Rana
      tadpoles and froglets under various experimental conditions.
AB  - The effect of ophthalmectomy (enucleation) on plasma melatonin in Rana tadpoles
      and froglets was studied under various experimental conditions to determine if
      ocular melatonin is released into the circulation from the eyes and to study the
      factors which might affect this process. Where operations occurred in early or
      mid-photophase on a 12 light:12 dark (12L:12D) cycle (light onset at 08:00 h),
      sampling in mid-light and mid-dark revealed that scotophase plasma melatonin was
      reduced at all developmental stages, with the more significant effects occurring
      before metamorphic climax. Experiments sampling prometamorphic tadpoles six times
      in a 24h period on 18L:6D, 12L:12D, or 6L:18D five days after enucleation also
      showed a significant lowering of plasma melatonin in the dark, so that the
      scotophase peak was virtually eliminated on all the LD cycles. These findings
      indicated that the reduction in plasma melatonin after bilateral eye removal was
      independent of the LD cycle and the metamorphic stage, and that it abolished the
      diel melatonin rhythm at the expense of the scotophase peak. Experiments carried
      out for 5 weeks suggested that compensatory secretion of melatonin by other
      organs after eye removal might partially restore the plasma melatonin level over
      time. Unilateral ophthalmectomy tended to reduce, but not eliminate, the night
      peak of plasma melatonin, and did not result in a compensatory increase in ocular
      melatonin in the remaining eye. Ophthalmectomized tadpoles exhibited darkening of
      the skin after the operation, which was not associated with a significant change
      in pituitary alpha-melanotropin. The findings overall indicate that the eyes in
      Rana tadpoles and froglets contribute up to somewhat over one-half of the
      circulating melatonin, particularly during the scotophase, and provide
      experimental evidence for ocular secretion into the blood for the first time in
      the Amphibia.

PMID- 16458310
TI  - Real-time PCR analysis of cytochrome P450 aromatase expression in zebrafish: gene
      specific tissue distribution, sex differences, developmental programming, and
      estrogen regulation.
AB  - In teleost fish, the predominant brain form of cytochrome P450 aromatase
      (P450aromB) is a neural marker of estrogen effect, and an entry point for
      studying the role of hormonal and environmental estrogens on neurodevelopment and
      neuroplasticity. As part of a project using zebrafish to investigate these
      issues, we developed and validated a rapid, sensitive, and reproducible real-time
      polymerase chain reaction (PCR) assay for quantifying and comparing P450aromB and
      P450aromA expression in unfertilized eggs, embryos/larvae, and dissected tissues
      of adult fish. Results confirm that P450aromB and -A predominate in brain and
      ovary, respectively, and further show that the degree of overlapping expression
      (ratio, B:A) is 100:1 in brain, 1:50 in ovary, 1:1 in eye, and 2:1 in testis. Sex
      differences were observed in eye only (female>male). When compared to whole
      ovaries, unfertilized eggs had similar levels of P450aromA but enrichment of
      P450aromB, which suggests preferential synthesis or accumulation in mature
      oocytes. Both of the maternally derived aromatase isoforms were rapidly degraded
      post-fertilization, but the onset of embryonic P450aromB expression (5 hpf) was
      much earlier than P450aromA (48 hpf), and reached higher maximum levels (e.g., 10
      fold at 72 hpf). Consistent with earlier reports, P450aromB but not -A was
      estrogen-inducible, but the estrogen response system in embryos was far more
      robust than in adults (>100- vs. <4-fold maximal induction, respectively).
      Application of this real-time PCR assay to measurement of P450aromB and -A in
      zebrafish embryos has utility for routine screening of chemicals and
      environmental samples for estrogen-like bioactivity and neural effects.

PMID- 16458311
TI  - Paternal responsiveness in biparental dwarf hamsters (Phodopus campbelli) does
      not require estradiol.
AB  - Males of the biparental hamster species Phodopus campbelli act as midwives and
      are responsive to an experimentally displaced pup. Males also have peripheral
      estradiol concentrations that are similar to conspecific females. Castration
      reduces peripheral estradiol, yet does not affect paternal responsiveness despite
      the known role of estradiol in maternal behavior. Synthesis of estradiol within
      the central nervous system, however, might not be affected by castration. Males
      received implants of osmotic pumps containing the aromatase inhibitor letrozole
      to reduce both peripheral and central estradiol concentrations. Though estradiol
      was effectively reduced, it had no effect on paternal responsiveness or
      reproductive success. Neither testosterone nor aggression directed towards an
      intruder was altered. Results support the emerging conclusion that estradiol is
      not required for the exceptional paternal behavior of male P. campbelli.

PMID- 16458312
TI  - Fecal corticosterone, body mass, and caching rates of Carolina chickadees
      (Poecile carolinensis) from disturbed and undisturbed sites.
AB  - We tested for hormonal and behavioral differences between Carolina chickadees
      (Poecile carolinensis) taken from a disturbed (recently logged) forest, an
      undisturbed forest, or a residential site. We measured fecal corticosterone and
      body mass levels in the field, and fecal corticosterone, body mass, and caching
      behavior in an aviary experiment. In the field, birds from the disturbed forest
      exhibited significantly higher fecal corticosterone levels than birds from either
      the undisturbed forest or from the residential site. Birds from the disturbed
      forest also exhibited lower body mass than those from the undisturbed forest but
      higher body mass than those from the residential site. Our aviary results suggest
      that these physiological differences between field sites are the result of short
      term responses to ecological factors: neither body mass nor fecal corticosterone
      levels varied between birds captured at different sites. Aviary sample sizes were
      sufficient to detect seasonal variation in fecal corticosterone (lowest in
      summer), body mass (highest in spring), and rate of gain in body mass (highest in
      winter). Under "closed-economy" aviary conditions (all food available from a
      feeder in the aviary), there were no site differences in the percent of seeds
      taken from the feeder that were cached. However, under "open-economy" conditions
      (food occasionally available ad libitum), significantly fewer seeds were cached
      by birds from the disturbed forest compared to the undisturbed or residential
      sites. On average, there was only a two-fold difference in population levels of
      fecal corticosterone. This difference is about the same as an increase in fecal
      corticosterone induced by a 2-h increase in food deprivation and cannot be
      considered to be an acute stress response to disturbance.

PMID- 16458313
TI  - Perinatal, non-aromatized androgen exposure produces male superiority in
      discriminating between odors of social importance: A commentary on "Enhanced
      urinary odor discrimination in female aromatase knockout (ArKO) mice" by Wesson
      et al.

PMID- 16458314
TI  - Protective role of eicosapentaenoate-lipoate (EPA-LA) derivative in combating
      oxidative hepatocellular injury in hypercholesterolemic atherogenesis.
AB  - The aim of the present study is to evaluate the effect of eicosapentaenoic acid
      (EPA), dl-alpha-lipoic acid (LA) and eicosapentaenoate-lipoate (EPA-LA)
      derivative on the atherogenic disturbances in hypercholesterolemic atherogenic
      animals. Eight groups of male Wistar rats were employed in this study, wherein
      four groups were fed with a high cholesterol diet (rat chow supplemented with 4%
      cholesterol and 1% cholic acid; HCD) for 30 days, among which, three groups of
      rats were also treated with either EPA (35 mg/kg body weight/day, oral gavage),
      LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body
      weight/day, oral gavage) commencing from 16th day of the experimental period. The
      remaining four groups served as control and EPA, LA and EPA-LA derivative treated
      drug controls. Abnormal increases in the levels of malondialdehyde, protein
      carbonyl and 8-hydroxy-2-deoxyguanosine, as well as depressed antioxidants
      status, were observed in hepatic tissue of HCD fed rats. HCD induced abnormal
      elevation in the activities of hepatic lactate dehydrogenase, aminotransferases
      and alkaline phosphatase (ALP) and was accompanied by increased hepatic
      cholesterol level and altered fatty changes in the histology of liver. These
      changes were restored partially in the EPA and LA administered groups. However,
      the combined derivative EPA-LA almost ameliorated the hypercholesterolemic
      oxidative changes in the HCD fed rats. The results of this study present
      oxidative injury induced by hypercholesterolemic diet and administration of the
      combination treatment of EPA-LA afforded sound protection against lipemic
      oxidative injury.

PMID- 16458315
TI  - Hyperlipidemia and surfactants: the liver sieve is a link.
AB  - Poloxamer 407 is a ubiquitous synthetic surfactant that causes massive
      hyperlipidemia and atherosclerosis in the rodent. The initial step in hepatic
      metabolism of lipoproteins is their transfer through 100-200 nm pores
      (fenestrations) in the liver sinusoidal endothelial cell, prior to receptor
      mediated uptake. The 'liver sieve hypothesis' emphasizes the role of these
      fenestrations in the regulation of lipoprotein disposition. Here we show that
      P407 causes dramatic defenestration of the liver sinusoidal endothelium in vivo.
      By 24h after intraperitoneal administration in mice, fenestrations were reduced
      by approximately 80% coincident with a 10-fold increase in plasma lipids.
      Moreover impulse-response experiments in the perfused rat liver showed that P407
      prevented the passage of small chylomicrons across the liver sinusoidal
      endothelium. Defenestration was also induced acutely with P407 in isolated liver
      sinusoidal endothelial cells, indicating this is a direct effect of P407 on
      fenestrations. The results establish the role of the porosity of the liver
      sinusoidal endothelial cell as a pivotal yet relatively unrecognised mechanism
      for hyperlipidemia. Furthermore, the results establish an intriguing mechanism
      for surfactant-induced hyperlipidemia. Thus the liver sieve is a new and untapped
      target for the treatment and prevention of hyperlipidemia.

PMID- 16458316
TI  - Accumulation of chylomicron remnants and impaired vascular reactivity occur in
      subjects with isolated low HDL cholesterol: effects of niacin treatment.
AB  - Fasting hypertriglyceridemia relates with high-density lipoprotein (HDL)
      cholesterol, but it is not known whether low HDL cholesterol is associated with
      disturbances of chylomicron metabolism. To clarify this issue this metabolism was
      studied in subjects with low HDL cholesterol together with vascular reactivity
      and evaluation of no-flush niacin treatment. Thirty men with HDL < 1.04 mmol/L
      and no other risk factors for coronary artery disease (CAD) and 11 normal
      controls with HDL > 1.04 mmol/L were studied. The plasma kinetics of a
      chylomicron-like emulsion labeled with 14C-cholesterol oleate (CO) and 3H
      triolein (TG) was determined and the fractional clearance rate (FCR, min(-1)) was
      calculated. Vascular reactivity was evaluated using high-resolution
      ultrasonography. CO FCR was markedly reduced in the low HDL group compared to
      controls (3.6 x 10(-3) +/- 5.1 x 10(-3) min(-1) versus 12.2 x 10(-3) +/- 8.4 x
      10(-3) min(-1), p < 0.001) but TG FCR was similar. Flow-mediated dilation (FMD)
      was diminished in low HDL (7.4 +/- 4.1 versus 12.8 +/- 4.6%, p < 0.001), whereas
      nitrate-mediated dilation was similar. Twenty-two low HDL subjects with reduced
      FMD were randomized into two groups, one given 1.5 g/day niacin and a placebo
      group. After 3-month treatment, plasma lipids and chylomicron kinetics were not
      changed by niacin treatment but FMD improved to normal values (5.44 +/- 1.89 to
      11.13 +/- 3.4%, p < 0.01). In conclusion, isolated low HDL cholesterol subjects
      may also bear chylomicron remnant accumulation and endothelial dysfunction, which
      highlight the importance of their preventive treatment.

PMID- 16458317
TI  - Modulation of lipoprotein metabolism by inhibition of sphingomyelin synthesis in
      ApoE knockout mice.
AB  - Plasma sphingomyelin (SM) has been suggested as a risk factor for coronary heart
      disease independent of cholesterol levels. A decrease of SM in lipoproteins is
      known to improve the activities of lecithin:cholesterol acyltransferase (LCAT)
      and lipoprotein lipase (LPL) in vitro. Inhibition of SM biosynthesis may reduce
      lipoprotein SM content and thus improve cholesterol distribution in lipoproteins
      by enhancing reverse cholesterol transport and clearance of triglyceride-rich
      lipoproteins. To examine this hypothesis, ApoE KO mice were fed a western diet
      and treated for 4 weeks with various concentrations of myriocin, a specific
      inhibitor of serine palmitoyltransferase. Myriocin treatment lowered plasma
      cholesterol and TG levels in a dose-dependent manner. In addition, myriocin
      treatment reduced cholesterol contents in VLDL and LDL and elevated HDL
      cholesterol. Observed lipid-lowering effects of myriocin were associated with
      suppression of HMG CoA reductase and fatty acid synthase via reduced levels of
      SREBP-1 RNA and protein. Induction of apoAI and lecithin:cholesterol
      acytransferase (LCAT) in the liver by myriocin was associated with an increased
      HDL. Lesion area and macrophage area were also diminished in the cuffed femoral
      artery of ApoE KO mice. In conclusion, inhibition of sphingolipid biosynthesis
      can be a novel therapeutic target for dyslipidemia and atherosclerosis.

PMID- 16458318
TI  - Fine tuning photoluminescence properties of CdSe nanoparticles by surface states
      modulation.
AB  - Fine control of the photoluminescence properties of CdSe nanoparticles (NPs)
      dispersed in CHCl3 is achieved by simple adjustment of the NPs concentration, and
      the wavelength of photoluminescence emission of CdSe NPs can be tuned within the
      nanometer accuracy. The mechanism of the process is proposed to be relevant to
      the modulation of the surface states of NPs by the concentration. This solution
      based approach offers an attractive and complementary process to the conventional
      band gap engineering of semiconductor NPs with fine tunable optical properties.

PMID- 16458319
TI  - Surfactant-mediated water transport at gelatin gel/oil interfaces.
AB  - We studied spontaneous emulsification (SE) at Water/Oil (W/O) interfaces, using
      several types of aqueous reservoirs immersed in dodecane plus Span80 surfactant.
      Above a threshold surfactant concentration C(SE), aqueous satellite droplets are
      formed at the W/O interface. Varying the aqueous reservoir size, from below 100
      microm (droplets) to centimeters (macroscopic phases), allowed investigating SE
      with complementary techniques. Release (rates) and size distributions for SE
      droplets were measured with microscopy. For gelled aqueous phases, water
      expulsion due to SE was quantified. Values for C(SE) were measured and were found
      to be higher for aqueous phases containing gelatin and/or NaCl. We also studied
      water exudation during network building and syneresis in aqueous gelatin gels
      immersed in dodecane/Span80. Below C(SE) (i.e., in the absence of SE) this
      process is still responsible for significant physico-chemical changes at the W/O
      interface. To study these in more detail, we performed atomic force microscopy
      experiments (in force-distance mode) on macroscopic gels. Both changes in the
      local elastic response and in the wettability of the AFM tip were detected.
      Together they suggest the formation of "water pockets" after prolonged (gel)
      setting times, along with a densification of the interfacial gelatin network.

PMID- 16458320
TI  - Temperature effect on the stability of bentonite colloids in water.
AB  - The stability of natural bentonite suspensions has been investigated as a
      function of temperature at pH 9 and ionic strength 10(-3) M. The sedimentation
      rate of the particles is directly related to their stability. The sedimentation
      kinetics was determined by examining the variation of particle concentration in
      solution with time. The observed kinetics for sedimentation is discussed
      quantitatively in terms of the potential energy between particles. The zeta
      potential of the particles was measured and the DLVO theory was used to calculate
      attractive and repulsive potentials. Experimental observations are consistent
      with DLVO model predictions and show that the stability of bentonite colloids
      increases with temperature. Differences with other colloidal systems can be
      attributed to the temperature dependence of the surface charge of bentonite
      particles.

PMID- 16458321
TI  - A novel flow-cytometry-based assay for quantification of affinity and avidity
      changes of integrins.
AB  - Cell adhesion plays an important role in cell-cell contact formation and cell
      migration. Thus, the assessment of cellular adhesiveness is one important feature
      when studying cell-mediated immune responses. The interaction of lymphocytes with
      other cell types such as antigen-presenting cells or vascular-endothelial cells
      occurs via adhesion molecules including L-selectin, VCAM-1 or ICAM-1. There are
      principally two mechanisms by which cell adhesion can be enhanced: namely changes
      in the affinity or avidity of receptor interactions. Conventional plate-based
      adhesion assays detect both forms. However, they do not permit discrimination
      between affinity- and avidity-mediated changes in the adhesiveness. Moreover,
      analysis of cell subpopulations requires cell separation prior to performance of
      the adhesion assay. Conventional flow-cytometry-based tests make it possible to
      determine changes in the affinity of integrins at the single cell level. However,
      they fail to quantify avidity-mediated adhesiveness. Here we describe a novel
      flow-cytometry-based assay, which allows the detection of both integrin-mediated
      affinity as well as avidity changes at the single cell level. This opens up the
      possibility of precisely characterizing the adhesive capacity of subpopulations
      in heterogeneous cell populations.

PMID- 16458322
TI  - Inhibition of the growth of Paenibacillus larvae, the causal agent of American
      foulbrood of honeybees, by selected strains of aerobic spore-forming bacteria
      isolated from apiarian sources.
AB  - The bacterium Paenibacillus larvae, the causative agent of American foulbrood
      disease of honeybee larvae, occurs throughout the world and is found in many
      beekeeping areas of Argentina. The potential as biocontrol agents of antagonic
      aerobic spore-forming bacteria isolated from honey samples and other apiarian
      sources were evaluated. Each isolate was screened against one strain of
      Paenibacillus larvae (ATCC 9545) by using a perpendicular streak technique. Ten
      randomly selected bacterial strains from the group that showed the best
      antagonistic effect to P. larvae ATCC 9545 were selected for further study. These
      were identified as Bacillus subtilis (m351), B. pumilus (m350), B. licheniformis
      (m347), B. cereus (mv33), B. cereus (m387), B. cereus (m6c), B. megaterium
      (m404), Brevibacillus laterosporus (BLAT169), B. laterosporus (BLAT170), and B.
      laterosporus (BLAT171). The antagonistic strains were tested against 17 P. larvae
      strains from different geographical origins by means of a spot test in wells. The
      analysis of variance and posterior comparison of means by Tukey method (P < 0.01)
      showed that the best antagonists were B. megaterium (m404), B. licheniformis
      (m347), B. cereus (m6c), B. cereus (mv33), and B. cereus (m387).

PMID- 16458324
TI  - Structure of the regulatory subunit of acetohydroxyacid synthase isozyme III from
      Escherichia coli.
AB  - The enzyme acetohydroxyacid synthase (AHAS) catalyses the first common step in
      the biosynthesis of the three branched-chain amino acids. Enzymes in the AHAS
      family generally consist of regulatory and catalytic subunits. Here, we describe
      the first crystal structure of an AHAS regulatory subunit, the ilvH polypeptide,
      determined at a resolution of 1.75 A. IlvH is the regulatory subunit of one of
      three AHAS isozymes expressed in Escherichia coli, AHAS III. The protein is a
      dimer, with two beta alpha beta beta alpha beta ferredoxin domains in each
      monomer. The two N-terminal domains assemble to form an ACT domain structure
      remarkably close to the one predicted by us on the basis of the regulatory domain
      of 3-phosphoglycerate dehydrogenase (3PGDH). The two C-terminal domains combine
      so that their beta-sheets are roughly positioned back-to-back and perpendicular
      to the extended beta-sheet of the N-terminal ACT domain. On the basis of the
      properties of mutants and a comparison with 3PGDH, the effector (valine) binding
      sites can be located tentatively in two symmetrically related positions in the
      interface between a pair of N-terminal domains. The properties of mutants of the
      ilvH polypeptide outside the putative effector-binding site provide further
      insight into the functioning of the holoenzyme. The results of this study open
      avenues for further studies aimed at understanding the mechanism of regulation of
      AHAS by small-molecule effectors.

PMID- 16458323
TI  - Differential cardiotoxic/cardioprotective effects of beta-adrenergic receptor
      subtypes in myocytes and fibroblasts in doxorubicin cardiomyopathy.
AB  - beta-Adrenoceptor (beta-AR) subtypes act through different signaling pathways to
      regulate cardiac function and remodeling. Previous in vivo data show a markedly
      enhanced cardiotoxic response to doxorubicin in beta2-/- mice, which is rescued
      by the additional deletion of the beta1-AR. We determined whether this
      differential response was myocyte specific by examining the effects of
      doxorubicin in myocytes and fibroblasts from WT and beta1, beta2 and beta1/beta2
      /- mice. Cells were exposed to doxorubicin at 1-50 microM and viability and
      apoptosis assessed at 6, 24 and 48 h. WT myocytes showed a time and dose
      dependent decrease in viability (42% decrease at 1 microM after 24 h). beta2-/-
      Myocytes showed a greater decrease in viability vs. WT (20.8% less at 6 h; 14%
      less at 24 h, P<0.05); beta1-/- and beta1/beta2-/- myocytes showed enhanced
      survival (beta1-/- 11%; beta1/beta2-/- 18% greater than WT, P<0.05). TUNEL
      staining demonstrated a similar differential susceptibility (WT 26% apoptotic
      nuclei, beta2-/- 45.9%, beta1/beta2-/- 16.8%, P<0.05). beta2-/- Fibroblasts also
      showed enhanced toxicity. Pertussis toxin pretreatment of WT cells decreased
      survival similar to the beta2-/-, suggesting a role for Gi signaling. JNK was
      differentially activated in beta2-/- myocytes after doxorubicin and its
      inhibition increased cardiotoxicity. In conclusion, the differential
      cardioprotective/cardiotoxic effects mediated by beta1 vs. beta2-AR subtypes in
      knockout mice are recapitulated in myocytes isolated from these mice. beta2-ARs
      appear to play a cardioprotective role, whereas beta1-ARs a cardiotoxic role.

PMID- 16458325
TI  - Evolution of the maturation rate collapses competitive coexistence.
AB  - Most theoretical studies on character displacement and the coexistence of
      competing species have focused attention on the evolution of competitive traits
      driven by inter-specific competition. We investigated the evolution of the
      maturation rate which is not directly related to competition and trades off with
      the birth rate and how it influences competitive outcomes. Evolution may result
      in the superior competitor becoming extinct if, initially, the inferior
      competitor has a lower, and the superior one a higher, maturation rate at the
      coexistence equilibrium. This counterintuitive result is explained by an
      explosive increase in the adult population of the inferior competitor as a result
      of the more rapid evolution of its maturation rate, which is caused by
      differences in the intensity and direction of selection on the maturation rates
      of the two species and in their adult densities, which are related to differences
      in their life histories. Thus, a life history trait trade-off with a competitive
      trait may cause a competitive ecological coexistence to collapse.

PMID- 16458326
TI  - Atractyloside and 5-hydroxydecanoate block the protective effect of puerarin in
      isolated rat heart.
AB  - The aim of the present study was to determine whether the clinically effective
      cardioprotection conferred by puerarin (Pue) against ischemia and reperfusion is
      mediated by mitochondrial transmembrane pores and/or channels. Hearts isolated
      from male Sprague-Dawley rats were perfused on a Langendorff apparatus and
      subjected to 30 min of global ischemia followed by 120 min of reperfusion. The
      production of formazan, which provides an index of myocardial viability, was
      measured by absorbance at 550 nm, and the level of lactate dehydrogenase (LDH) in
      the coronary effluent was determined. In this model, Pue (0.0024-2.4 mmol/l) had
      a dose-dependent, negatively inotropic effect. Pretreatment with Pue at 0.24
      mmol/l for 5 min before ischemia increased myocardial formazan content, reduced
      LDH release, improved recovery of left ventricular end-diastolic pressure and
      rate-pressure product (left ventricular developed pressure multiplied by heart
      rate) during reperfusion. Administration of atractyloside (20 micromol/l), an
      opener of the mitochondrial permeability transition pore, for the first 20 min of
      reperfusion, and 5-hydroxydecanoate (100 micromol/l), the mitochondrial-specific
      ATP-sensitive potassium channel blocker, for 20 min before ischemia, attenuated
      the protective effects of Pue. In mitochondria isolated from hearts pretreated
      with 0.24 mmol/l Pue for 5 min, a significant inhibition of Ca(2+)-induced
      swelling was observed, and this inhibition was attenuated by 5-hydroxydecanoate.
      In isolated ventricular myocytes, pretreatment with Pue prevented ischemia
      induced cell death and depolarization of the mitochondrial membrane, and
      atractyloside and 5-hydroxydecanoate attenuated the effects of Pue. These
      findings indicate that puerarin protects the myocardium against ischemia and
      reperfusion injury via inhibiting mitochondrial permeability transition pore
      opening and activating the mitochondrial ATP-sensitive potassium channel.

PMID- 16458327
TI  - Merit of physical exercise to reverse the higher gene expression of hepatic
      phosphoenolpyruvate carboxykinase in obese Zucker rats.
AB  - Effects of endurance training on the phosphoenolpyruvate carboxykinase (PEPCK), a
      rate-limiting enzyme of gluconeogenesis, were studied in the obese Zucker rats.
      We used a moderate exercise program consisting of treadmill running at 20 m/min
      and 0-degree gradient for 1 h/day, 7 days/week, for 8 weeks. At the end of the
      experimental period, insulin action on glucose disposal rate was measured using
      the glucose-insulin index, the product of the areas under the curve of glucose
      and insulin during the intraperitoneal glucose tolerance test. Furthermore,
      changes of hepatic PEPCK gene expression were detected using reverse
      transcriptase polymerase chain reaction to assay the mRNA level and Western blot
      analysis to detect the protein level. Different to sedentary obese rats, an
      elevation in the value of glucose-insulin index from the exercised obese rats
      declined, indicating the marked effect of regular moderate exercise on the
      improvement of insulin sensitivity in this insulin resistant animal model.
      Moreover, the diabetes-related elevation in mRNA level and protein content of
      hepatic PEPCK were observed in non-exercise obese groups but they were markedly
      reduced by exercise training. In addition, chronic exercise training enhanced the
      insulin sensitivity of lean Zucker rats, since the value of glucose-insulin index
      was lower than that of untrained lean groups. Also, the hepatic PEPCK gene
      expressions both the mRNA and protein levels were reduced in exercised lean
      Zucker rats as compared with their sedentary littermates. These results suggest
      that modulation of hepatic PEPCK gene expression by chronic exercise training
      might be related to the enhancement of insulin sensitivity. Thus, endurance
      exercise training could aid in the prevention and/or treatment of individuals
      with insulin resistance.

PMID- 16458329
TI  - Pulse replications and spatially differentiated structure formation in one
      dimensional lattice dynamical system.
AB  - Replication and differentiation of pulses are studied through a simple dynamical
      system on a one-dimensional lattice. Depending on the parameter values, our
      proposed system exhibits the following types of pulse replications: (I) each
      pulse replicates by itself, (II) each pulse replicates if two or more pulses
      collide each other, and (III) pulses replicate by the organization of pulse
      generators. Moreover, replicated pulses construct the spatial-temporal pattern
      when the number of pulses is large. By selecting local objects in such spatial
      temporal patterns and replanting them numerically, it is found that there are two
      types differentiated local structures: one that continues the production of
      pulses and the other that does not.

PMID- 16458328
TI  - Anti-cancer effect and structural characterization of endo-polysaccharide from
      cultivated mycelia of Inonotus obliquus.
AB  - The endo-polysaccharide extracted from mycelia of Inonotus obliquus (Pers.:Fr.)
      Pil. (Hymenochaetaceae) is a specific activator of B cells and macrophages.
      However, the in vivo anti-cancer effects and the chemical structure of the endo
      polysaccharide are unknown. We purified the endo-polysaccharide, investigated its
      anti-cancer effects via in vitro and in vivo assays, and performed a structural
      characterization. The endo-polysaccharide was extracted from I. obliquus mycelia
      cultivated in a 300-l pilot fermenter, followed by hot water extraction and
      ethanol precipitation. Purification was achieved by DEAE-cellulose ion-exchange
      chromatography and gel-permeation chromatography. Chemical analysis revealed that
      the purified endo-polysaccharide is an alpha-linked fucoglucomannan with a
      molecular weight of approximately 1,000 kDa. The anti-cancer activities of the
      endo-polysaccharide against various types of tumor cells were determined. No
      direct toxicity against either cancer or normal cells was observed.
      Intraperitoneal administration of the endo-polysaccharide significantly prolonged
      the survival rate of B16F10-implanted mice, resulting in a 4.07-fold increase in
      the survival rate at a dose of 30 mg/kg/day. After 60 days of feeding,
      approximately 67% of the initial number of mice survived with no tumor incidence
      based on macroscopic examination. These results indicate that the anti-cancer
      effect of endo-polysaccharide is not directly tumorcidal but rather is immuno
      stimulating.

PMID- 16458331
TI  - Assessment of peripheral DNA damage by alkaline comet assay in maintenance
      hemodialysis subjects with hepatitis C infection.
AB  - Despite the high prevalence of hepatitis C infection among hemodialysis subjects,
      there is no information concerning the DNA damage of hepatitis C (+) hemodialysis
      subjects. We aimed to find out if there is any additional effect of hepatitis C
      infection on peripheral DNA damage in maintenance hemodialysis subjects. Fifteen
      hepatitis C (+) and 22 hepatitis C (-) hemodialysis subjects, 21 hepatitis C
      subjects without renal disease, and 22 healthy controls were enrolled. Peripheral
      DNA damage was assayed using alkaline comet assay. Median DNA damage levels of
      the study groups were as follows: hepatitis C (+) maintenance hemodialysis
      subjects, 88 (0-232); hepatitis C (-) maintenance hemodialysis subjects, 58 (0
      228); hepatitis C (+) subjects without renal disease, 112 (44-252); controls, 26
      (0-72). DNA damage level was significantly higher among hepatitis C (+) subjects
      without renal disease than hepatitis C (-) maintenance hemodialysis subjects and
      healthy controls (both p<0.05/6). Both maintenance hemodialysis subjects with and
      without HCV infection had significantly higher DNA damage level than healthy
      controls (both p<0.05/6). DNA damage level was comparable between hepatitis C (+)
      subjects without renal disease and HCV (+) hemodialysis subjects, and between
      hemodialysis subjects with and without hepatitis C infection (all p>0.05/6).
      Linear regression analysis revealed that hepatitis C infection was the only
      independent factor in predicting the peripheral DNA damage (p<0.05, beta=0.395).
      Each one of end-stage renal disease and hepatitis C infection significantly
      increases DNA damage level. However, in hemodialysis subjects, hepatitis C
      infection does not cause significant additional increase in DNA damage level, and
      it may be partly due to protective effect of hemodialysis on hepatitis C
      infection.

PMID- 16458330
TI  - Distributions of five common point mutants in the human tracheal-bronchial
      epithelium.
AB  - The mutations C742T, G746T, G747T in the TP53 gene and G35T in the KRAS gene have
      been repeatedly found in sectors of human tumors by direct DNA sequencing. The
      mutation G508A in the HPRT1 gene has been repeatedly found among peripheral T
      lymphocytes by clonal expansion under selective conditions. To discover if these
      mutations also occur frequently in normal tissues from which tumors arise, we
      have developed and validated allele-specific mismatch amplification mutation
      assays (MAMA) for each mutation. Reconstruction experiments demonstrated
      linearity in the range of 9-3000 mutant alleles among 3 x 10(6) wild-type
      alleles. The cumulative distributions of all negative controls established robust
      detection limits (P<0.05) of 34-125 mutants per 10(6) copies assayed depending on
      the mutation. One hundred and seventy-seven micro-anatomical samples of
      approximately (0.5-6)x10(6) tracheal-bronchial epithelial cells from nine non
      smokers were assayed representing en toto the equivalent of approximately 1.6
      human bronchial trees to the fifth bifurcation. Statistically significant mutant
      copy numbers were found in 257 of 463 assays. Clusters of mutant copies ranged
      from 10 to 1000 in 239/257 positive samples. As all five point mutations were
      detected at mutant fractions of >10(-5) in two or more lungs, we infer that they
      are mutational hotspots generated in lung epithelial stem cells. As the cancer
      associated mutations did not differ in cluster size distribution from the HPRT1
      mutation, we infer that none of the mutations conferred a growth advantage to
      somatic heterozygous clusters or maintenance turnover units. Specific mutants
      appeared in very large copy numbers, 1000-35,000, in 18/257 positive assays.
      Various hypotheses to account for the observed cluster size distributions are
      offered.

PMID- 16458332
TI  - Single strand DNA breaks in rat brain cells exposed to microwave radiation.
AB  - This investigation concerns with the effect of low intensity microwave (2.45 and
      16.5 GHz, SAR 1.0 and 2.01 W/kg, respectively) radiation on developing rat brain.
      Wistar rats (35 days old, male, six rats in each group) were selected for this
      study. These animals were exposed for 35 days at the above mentioned frequencies
      separately in two different exposure systems. After the exposure period, the rats
      were sacrificed and the whole brain tissue was dissected and used for study of
      single strand DNA breaks by micro gel electrophoresis (comet assay). Single
      strand DNA breaks were measured as tail length of comet. Fifty cells from each
      slide and two slides per animal were observed. One-way ANOVA method was adopted
      for statistical analysis. This study shows that the chronic exposure to these
      radiations cause statistically significant (p<0.001) increase in DNA single
      strand breaks in brain cells of rat.

PMID- 16458333
TI  - Regulation of CART mRNA in the rat nucleus accumbens via D3 dopamine receptors.
AB  - A variety of studies indicate that CART in the nucleus accumbens (NAcc) is
      involved in the action of psychostimulants. In order to understand in more detail
      if and how dopamine is involved in the regulation of CART mRNA in the NAcc, the
      present studies of individual receptors were performed. The D1 agonist,
      dihydrexidine, and the D1 antagonist, SCH23,390, were administered separately and
      in combination to adult male rats; however, no changes were found in CART mRNA as
      measured by in situ hybridization. The D2/3 agonist, quinpirole, was administered
      either separately or in combination with the D2 selective antagonist, L741,626,
      or the D3 selective antagonist, GR103,691. Quinpirole produced a decrease in CART
      mRNA of up to 43%. This effect was blocked by pretreatment with the D3 antagonist
      GR103, 691, but not by the D2 antagonist, L741,626. CART peptide levels showed a
      similar decrement after acute quinpirole. CART mRNA levels in the NAcc of D3
      mutant mice were found to be higher than that in wild-type animals, but treating
      the mutants with quinpirole failed to produce a decrease in CART expression like
      that observed in wild-type rodents. These findings demonstrate that CART is
      regulated by dopamine in the NAcc, at least partly by D3 dopamine receptors.

PMID- 16458334
TI  - The cortical network for eye-hand coordination and its relevance to understanding
      motor disorders of parietal patients.
AB  - Cortical neurons in both superior (SPL) and inferior (IPL) parietal lobules are
      modulated by a variety of signals concerning planning and execution of eye and
      hand movement. Thanks to these properties, parietal neurons are ideally suited
      for eye-hand coordination during reaching. In SPL, a fundamental feature of
      neurons is the invariance of their directional tuning properties across tasks
      that require different forms of spatial relationships between the eye and the
      hand. In such conditions, the orientation of the preferred directions (PDs) of
      individual SPL cells cluster within a limited sector of space, the global tuning
      field (GTF), to be regarded as an ideal frame to dynamically match eye and hand
      signals on the basis of the orientation of their PDs. At the population level,
      the mean vectors of the GTF cover the direction continuum in a uniform fashion.
      These neurons are part of a parietal network richly interconnected with the
      premotor and motor areas of the frontal lobe. Thus, the reaching disorders of
      patients with optic ataxia might be interpreted as a consequence of the breakdown
      of the combinatorial mechanisms of the GTF of parietal neurons, and of their
      interplay with premotor cortex. In IPL, the main feature of eye and/or hand
      related neurons is the uneven distribution of their PDs, that mostly point toward
      the contralateral space. This anisotropy of the representation of directional
      motor space might explain the movement disorders that characterize directional
      hypokinesia in neglect patients. In conclusion, the study of the dynamic
      properties of parietal neurons and of their relationships with the premotor
      cortex via cortico-cortical connections provides a basis for an interpretation of
      movement disorders of parietal patients from a neurophysiological perspective.

PMID- 16458335
TI  - Food restriction affects reproduction and survival of F1 and F2 offspring of Rat
      like hamster (Cricetulus triton).
AB  - Food restriction in parent may have long-term consequence on the reproductive
      capabilities of the offspring, and these consequences may, in turn, play an
      important role in population regulation. In this paper, we systematically
      examined the effect of maternal food restriction on reproduction and survival of
      maternal individuals, and F1 and F2 offspring of Rat-like hamsters (Cricetulus
      triton). Food restriction to 75% of that eaten by ad libitum-fed hamsters (75%
      FR) did not affect the reproductive organs and hormone concentration of maternal
      females, but 50% FR significantly reduced the size of ovarian organ and estradiol
      concentration of maternal females. 75% FR significantly reduced the testosterone
      concentration of maternal males; 50% FR significantly reduced both the size of
      epididymides and concentration of testosterone of maternal males. 70% FR in
      maternal females significantly reduced the sizes of reproductive organs and
      hormone concentrations of both their male and female F1 offspring. FR maternal
      females also produced significantly more male than female F1 offspring. The sizes
      of reproductive organs or hormone concentration of F2 males of maternal FR
      continued to significantly decline, but no such effect was observed in F2
      females. However, the number of F2 offspring per F1 female of FR maternal females
      at birth became significantly smaller and with significantly more males than
      females. Survival to weaning of F1 and F2 offspring of FR maternal females became
      significantly smaller during the period from birth to weaning. Thus, the effects
      of maternal food restriction could be an important mechanism to explain the
      prolonged low population density that is commonly observed after the population
      crash of this species.

PMID- 16458336
TI  - Does modification of olfacto-gustatory stimulation diminish sensory-specific
      satiety in humans?
AB  - Alimentary sensory pleasure is an important factor in ingestive behavior. Renewal
      of olfacto-gustatory pleasure by introducing new foods or through seasoning of
      previously consumed food might increase intake. OBJECTIVES: To explore whether
      sensory-specific satiety (SSS) for a food could be modulated, either by
      introducing a novel food or by a modification of sensory stimulation via
      seasoning the food just eaten. METHODS: 180 out of 242 subjects were distributed
      over 3 experiments involving ad libitum intake of one of 6 fresh foods (cucumber,
      tomato, pineapple, banana, peanut, pistachio). Blindfolded subjects reported
      their sensations for the foods on 3 parameters before and after intake of an
      olfactorily chosen food: Olfactory pleasure (OP), Specific appetite (SA) and
      Stimulus-Induced Salivation (SIS). EXP. 1: One chosen food was repeatedly
      presented orthonasally and rated before and after it was eaten. EXP. 2: A second
      food was olfactorily chosen and ingested after the first one. EXP. 3: The same
      food was offered again after seasoning. RESULTS: 2 min after ingestion, food
      intake was limited by SSS. OP, SA, SIS correlated with each other for eaten and
      non-eaten foods. OP for non-eaten foods increased (p<0.01) after ingestion of the
      chosen food to specific satiety. When the food just eaten was seasoned, OP
      increased (p<0.01) and led to additional intake (80% of first intake).
      CONCLUSION: A reduction in SSS after introduction of a new flavor or after
      seasoning an ingested food was observed. Such a reduction has not previously been
      reported. This could hint at how food sensory variation leads to over
      consumption.

PMID- 16458337
TI  - Incidence of neutropenia in HIV-infected African adults receiving co-trimoxazole
      prophylaxis: a 6-year cohort study in Abidjan, Cote d'Ivoire.
AB  - In a placebo-controlled trial of co-trimoxazole prophylaxis in Cote d'Ivoire,
      neutropenia was the most frequent short-term side effect. The long-term incidence
      of neutropenia in sub-Saharan African adults receiving co-trimoxazole has never
      been reported. We followed a prospective cohort of HIV-infected adults receiving
      co-trimoxazole (sulphamethoxazole 800 mg/trimethoprim 160 mg daily) in Abidjan.
      Grades of neutropenia were successively defined as at least one absolute
      neutrophil count (ANC) of: <1500/mm(3) (severity grade >/=1), <1000/mm(3) (grade
      >/=2), <750/mm(3) (grade >/=3) or <500/mm(3) (grade 4). In total, 533 adults were
      followed-up during 1450 person-years, with a total of 3154 ANCs. The probability
      of remaining free of neutropenia at 48 months was 0.29 (95% CI 0.23-0.34) for
      grade >/=1, 0.64 (95% CI 0.60-0.71) for grade >/=2, 0.82 (95% CI 0.77-0.86) for
      grade >/=3 and 0.96 (95% CI 0.93-0.99) for grade 4. The only factor significantly
      associated with a higher rate of all grades of neutropenia was a low baseline CD4
      count. There was no association between any grade of neutropenia and the global
      risk of serious morbidity during the study period. In adults receiving co
      trimoxazole in Abidjan, mild neutropenia is a common observation with no evidence
      of negative clinical consequences. The consequences of associating co-trimoxazole
      with other haematotoxic drugs should be carefully assessed.

PMID- 16458338
TI  - Molecular cloning of the major lethal toxins from two kraits (Bungarus flaviceps
      and Bungarus candidus).
AB  - The major lethal toxins present in the venoms of the red-headed krait, Bungarus
      flaviceps, and the Malayan krait, Bungarus candidus, have both been purified.
      Each consists of two polypeptide chains, A and B, joined by a disulfide bond. In
      the present study, primary structures of these toxins were determined by Edman
      degradation and by nucleotide sequencing of the cDNA clones. Amino acid
      sequencing of the N-terminus and enzymatically digested peptides revealed that
      the A and B chains were highly homologous to those of beta-bungarotoxins (beta
      Bgts) from Bungarus multicinctus, respectively. We isolated cDNA clones encoding
      the A and B chains from both B. flaviceps and B. candidus venom gland cDNA
      libraries using probes designed based on the cDNA sequence of beta-Bgt from B.
      multicinctus. Two isoforms of the A chain and one isoform of the B chain were
      obtained from B. flaviceps, and one isoform of the A chain and two isoforms of
      the B chain were obtained from B. candidus. Both of the two A chains from B.
      flaviceps are made up of 119 amino acids and comprise 15 cysteine residues, while
      the A chains of beta-Bgt from other Bungarus species including B. candidus
      comprise 13 cysteine residues. The B chains from both species are composed of 59
      amino acid residues and comprise seven cysteines. In conclusion, the lethal toxin
      from B. flaviceps is considered to be a novel isoform of beta-Bgt, which has a
      different pattern of cysteine residues from known beta-Bgts.

PMID- 16458339
TI  - Interaction of a plasminogen activator proteinase, LV-PA with human alpha2
      macroglobulin.
AB  - Lachesis venom plasminogen activator (LV-PA) is a 33-kDa serine proteinase
      isolated from bushmaster (Lachesis muta muta) snake venom, which activates the
      fibrinolytic system in vitro. This study has examined the effect of the plasma
      proteinase inhibitor alpha2-macroglobulin (alpha2-M) towards LV-PA and compares
      it with the effect on tissue type plasminogen activator (t-PA). The proteolytic
      activity of LV-PA alone or previously incubated with human plasminogen (Plg) on
      the large molecular mass protein substrates, dimethylcasein (DMC) and fibrinogen
      (Fg) was completely inhibited by human alpha2-M. However, the synthetic peptides
      Tos-Gly-Pro-Lys-pNA and H-D-Pro-Phe-Arg-pNA (S-2302) were hydrolyzed with almost
      no reduction in rate. At pH 7.4 and 37 degrees C the proteinase (0.15 microM over
      15 min) interacted with alpha2-M, and each mole of alpha2-M bound 2 mol of
      enzyme. Sodium dodecyl sulfate gel electrophoresis of reduced samples showed that
      the interaction of alpha2-M with either LV-PA or t-PA preincubated with Plg
      resulted in the formation of approximately 90 kDa fragments and high molecular
      mass complexes (Mr 180 kDa), generated by the incubation mixture (LV-PA or t-PA)
      and Plg. The data suggest that LV-PA is a direct-type PA and its fibrinolytic
      effect can be reduced by alpha2-M in vivo.

PMID- 16458340
TI  - Kinetic and mechanistic characterization of the Sphingomyelinases D from
      Loxosceles intermedia spider venom.
AB  - Envenomation by arachnids of the genus Loxosceles leads to local dermonecrosis
      and serious systemic toxicity mainly induced by sphingomyelinases D (SMase D).
      These enzymes catalyze the hydrolysis of sphingomyelin resulting in the formation
      of ceramide-phosphate and choline as well as the cleavage of lysophosphatidyl
      choline generating the lipid mediator lysophosphatidic acid. We have, previously,
      cloned and expressed two functional SMase D isoforms, named P1 and P2, from
      Loxosceles intermedia venom and comparative protein sequence analysis revealed
      that they are highly homologous to SMase I from Loxosceles laeta which folds to
      form an (alpha/beta)8 barrel. In order to further characterize these proteins, pH
      dependence kinetic experiments and chemical modification of the two active SMases
      D isoforms were performed. We show here that the amino acids involved in
      catalysis and in the metal ion binding sites are strictly conserved in the SMase
      D isoforms from L. intermedia. However, the kinetic studies indicate that SMase
      P1 hydrolyzes sphingomyelin less efficiently than P2, which can be attributed to
      a substitution at position 203 (Pro-Leu) and local amino acid substitutions in
      the hydrophobic channel that could probably play a role in the substrate
      recognition and binding.

PMID- 16458341
TI  - CCAAT/enhancer-binding proteins modulate human T cell leukemia virus type 1 long
      terminal repeat activation.
AB  - CCAAT/enhancer-binding protein (C/EBP) basic region/leucine zipper (bZIP)
      transcription factors have been shown to form heterodimers with cAMP-responsive
      element binding protein 2 (CREB-2), a transcription factor involved in regulating
      basal and Tax-mediated transactivation of the human T cell leukemia virus type 1
      (HTLV-1) long terminal repeat (LTR). In cells of the monocyte-macrophage lineage
      (proposed to play a role in HTLV-1 pathogenesis as an accessory target cell),
      several members of the C/EBP family are expressed at high levels and may have
      functional impact on both basal and Tax-mediated transactivation of the HTLV-1
      LTR. Basal activation of the HTLV-1 LTR was enhanced by overexpression of
      C/EBPbeta, C/EBPdelta, or C/EBPepsilon, whereas transactivation of the LTR by Tax
      was inhibited by overexpression of C/EBPalpha and C/EBPbeta. Inhibition of Tax
      mediated transactivation of the HTLV-1 LTR was co-activator-independent, did not
      require C/EBP binding to the Tax-responsive elements, and may involve
      heterodimerization with CREB factors.

PMID- 16458342
TI  - Transcriptional silencing of the mouse mammary tumor virus promoter through
      chromatin remodeling is concomitant with histone H1 phosphorylation and histone
      H3 hyperphosphorylation at M phase.
AB  - We examined histone phosphorylation and their effects on glucocorticoid receptor
      (GR)-mediated activation of the mouse mammary tumor virus promoter (MMTV) in
      synchronized cells. In vivo protein expression studies suggest that both histones
      H1 and H3 are highly phosphorylated in mitotic-arrested cells in which GR is
      unable to remodel chromatin and recruit transcription factor NF1 to the promoter.
      Postmitotic cells show an open chromatin structure and efficient binding of NF1
      to the promoter accompanied by reversing histone H1 and H3 phosphorylation level.
      In contrast, the acetylation status of histone H3 and H4 did not change in either
      condition. These results suggest that hyperphosphorylation of histone H1 and H3
      leads to inhibition of GR-mediated chromatin remodeling and inactivation of MMTV
      by preventing the association of transcription factors to the promoter in vivo.

PMID- 16458343
TI  - Routine analysis of off-flavor compounds in water at sub-part-per-trillion level
      by large-volume injection GC/MS with programmable temperature vaporizing inlet.
AB  - "Earthy-musty" off-flavor problem in water samples are due to organic compounds
      present at the sub-part-per-trillion level. Most of the developments in the
      analysis of tastes and odorous compounds focus on the extraction pre
      concentration technique, with detection at picogram per liter level of the earthy
      musty off-flavor compounds difficult to be achieved. The objective of this study
      is to develop a new method involving the large-volume injection (LVI) GC/MS via
      programmable temperature vaporizing (PTV) inlet and continuous liquid-liquid
      extraction, to attain analytical sensitivity equal to or better than olfactory
      sensitivity. Six "earthy-musty" organic compounds, 2-methylisoborneol (MIB),
      geosmin, 2,4,6-trichloroanisole, 2,3,6-trichloroanisole, 2,3,4-trichloroanisole
      and 2,4,6-tribromoanisole, were used as probes for this study. It was found that
      LVI via PTV could greatly improve system sensitivity towards off-flavor compound
      detection. Variable instrument conditions and sample preparation conditions were
      studied in detail. This reliable and efficient method has been optimized and
      validated. The method detection limit were found to be from 35 to 70 pg/L for
      haloanisoles, 50 pg/L for geosmin and 0.34 ng/L for MIB, with relative standard
      deviation of calibration curve ranging from 4.7% to 15.1% and recovery ranging
      from 58% to 96%. This method has been successfully applied to test off-flavor
      compounds in different types of water samples with satisfactory results.

PMID- 16458344
TI  - Levels and trends of brominated flame retardants in the Arctic.
AB  - Polybrominated diphenyl ethers (PBDEs) containing two to seven bromines are
      ubiquitous in Arctic biotic and abiotic samples (from zooplankton to polar bears
      (Ursus maritimus) and humans; air, soil, sediments). The fully brominated
      decabromodiphenyl ether (BDE-209), hexabromocyclododecane (HBCD),
      tetrabromobisphenol A (TBBPA) and polybrominated biphenyls (PBBs) are also
      present in biotic and abiotic samples. Spatial trends of PBDEs and HBCD in top
      predators are similar to those seen for polychlorinated biphenyls (PCBs) and
      indicate western Europe and eastern North America as source regions.
      Concentrations of tetra- to heptaBDEs have increased significantly in North
      American and Greenlandic Arctic biota and in Greenland freshwater sediments
      paralleling trends seen further south. For BDE-209, increasing concentrations in
      Greenlandic peregrine falcons (Falco peregrinus) and in dated lake sediment cores
      in the Canadian Arctic have been seen during the 1990s. BDE-47, -99, -100 and 
      153 are observed to biomagnify in Arctic food webs. summation operatorPBDE
      concentrations in Arctic samples are lower than in similar sample types from more
      southerly regions and are one or more orders of magnitude lower than summation
      operatorPCB concentrations except for some levels for air. Air and harbor
      sediment results for PBDEs indicate that there are local sources near highly
      populated areas within the Arctic. Findings of PBBs on moss and TBBPA on an air
      filter, and that both are found in biota at high trophic levels indicates that
      these compounds may also reach the Arctic by long-range atmospheric transport.
      Based on the evidence of their presence in the Arctic and indications that most
      if not all are undergoing long-range transport, these brominated flame retardants
      (BFRs) have characteristics that qualify them as POPs according to the Stockholm
      Convention.

PMID- 16458345
TI  - An intercalibration study on organobromine compounds: Results on polybrominated
      diphenylethers and related dioxin-like compounds.
AB  - An intercalibration study on organobromine compounds has been conducted to
      evaluate the accuracy and reliability in the analysis of brominated flame
      retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) and their
      related compounds like polybrominated and monobromo-polychlorinated
      dibenzodioxins and -furans (PBDDs/DFs, MoBPCDDs/DFs). This paper reports the
      results for these compounds in 'Mixed Standard Solutions' and 'Air-Dried
      Sediment'. The relative standard deviations (RSDs) for PBDEs, PBDDs/DFs and
      MoBPCDDs/DFs in mixed standard solutions ranged from 9% to 24%, 4% to 20% and 8%
      to 27%, respectively. The results of this study are better than those reported in
      earlier international interlaboratory studies due to general improvement in
      analytical methods and an increasing number of available authentic standards,
      particularly for PBDEs. In the analysis for higher brominated compounds such as
      octabromodibenzodioxin, the participants were advised to optimize the calibration
      curves befitting the range of concentrations found in samples because variation
      of relative response factors was noted. The results for 'Air-Dried Sediment' were
      also reasonable with RSDs from 10% to 38% for PBDEs, 8% to 38% for PBDDs/DFs and
      17% to 36% for MoBPCDDs/DFs. In the sediment sample, possible errors in the
      sample pretreatment and/or interference by other compounds/impurities were
      indicated. The concentrations of pentabromodiphenylether, BDE100, varied more
      than the other PBDE isomers due to its poor separation in some chromatographic
      conditions. In addition, interference by PBDEs was observed in the analysis for
      PBDFs. Potential degradation/secondary formulation of PBDEs and PBDFs during the
      Soxhlet extraction were suggested when copper powder was added into the sediment
      samples. Inspite of these observations, the results in this study are better than
      those reported in other interlaboratory studies due to the advice given to
      participants for improving the results. Compared with the results for PCDDs/DFs
      (5-23% RSDs) and Co-PCBs (6-24% RSDs), the RSDs for most of the organobromine
      compounds were high, indicating an immature QA/QC approach for the analysis of
      PBDEs and related compounds in comparison to common chlorinated dioxins.

PMID- 16458346
TI  - Evaluation of accelerated dechlorination of p,p'-DDT in acidic paddy soil.
AB  - The reductive dechlorination and behavior of p,p'-dichlorodiphenyltrichloroethane
      (p,p'-DDT) was investigated in a paddy soil. Treatment with 5% (w/w) metallic
      iron (Fe(0)) resulted in sharp decrease of p,p'-DDT, whereas there was no extra
      effect when 2% (w/w) aluminum sulfate (Al(2)(SO(4))(3)) was added to the Fe(0)
      treatment. These results suggest that Fe(0) could effectively promote the
      reductive dechlorination of p,p'-DDT and its metabolites while Al(2)(SO(4))(3)
      did not show any effect on those processes. Furthermore, p,p'-DDT and its
      daughter compounds inhibited holistic soil respiration greatly at first but could
      be metabolized by certain species of indigenous microorganisms after a period of
      adaptation time in the soil. When treated with Fe(0), the polluted soil produced
      much less CO(2) while the addition of Al(2)(SO(4))(3) counteracted its negative
      effect to much extent.

PMID- 16458348
TI  - Abstracts presented for the 37th Annual Meeting of the Society of Gynecologic
      Oncologists, March 22-26, 2006, Palm Springs, California, USA.

PMID- 16458347
TI  - C47T polymorphism in manganese superoxide dismutase (MnSOD), antioxidant intake
      and survival.
AB  - INTRODUCTION AND OBJECTIVE: Manganese superoxide dismutase (MnSOD), an enzyme
      that catalyzes superoxide radical quenching, is hypothesized to protect against
      premature aging. A C47T transition in the MnSOD gene may affect the enzyme's
      distribution to the mitochondrion, a site of high oxidative stress. We examined
      the association between this polymorphism and survival. METHODS: Individuals who
      donated a blood sample to the CLUE I and II campaigns in 1974 and 1989,
      respectively, and completed a food frequency questionnaire in 1989 (N=6151) were
      included in the analysis. Hazard ratios (HR) and 95% confidence intervals (CI)
      were calculated by Cox proportional hazards models. Mortality follow-up extended
      from 1989 to 2002. RESULTS: MnSOD genotype distributions were 27% CC (wildtype
      homozygotes), 50% CT (heterozygotes) and 23% TT (variant homozygotes). TT and CT
      genotypes compared to the CC genotype were not associated with all-cause or
      cardiovascular disease mortality. A slight, but non-statistically significant
      higher risk of cancer mortality was observed for the CT (HR=1.13, 95% CI: 0.86
      1.49) and TT (HR=1.24, 95% CI: 0.90-1.70) genotypes compared to CC genotype (p
      trend=0.19). CONCLUSION: We did not observe an association between the C47T
      polymorphism in the MnSOD gene and survival. These null associations were not
      modified by fruit and vegetable intake, cigarette smoking status, or body mass
      index.

PMID- 16458349
TI  - Identification of 2,3-epoxymethacrylic acid as an intermediate in the metabolism
      of dental materials in human liver microsomes.
AB  - OBJECTIVES: In previous studies it could be demonstrated that methacrylic acid
      (MA) is an intermediate in the metabolism of unpolymerized dental comonomers,
      released from dental restorative materials. This study was performed to identify
      the possible dental material intermediate 2,3-epoxymethacrylic acid (2,3-EMA)
      from MA in human liver microsomes. Most epoxy compounds are regarded as highly
      toxic substances. METHODS: The formation and hydrolysis were studied in defined
      systems containing only MA and human liver microsomes at 37 degrees C. Hydrolysis
      was inhibited by cyclohexene oxide, a competitive inhibitor of epoxide hydrolase.
      The reaction product 2,3-EMA was analyzed by the headspace gas chromatography
      mass spectrometry. After 5, 30, and 60 min samples were taken and analyzed.
      RESULTS: For the reaction of MA to 2,3-EMA the average conversion rate was about
      5% within 1h. It was found that without cyclohexene oxide the rate constant of
      enzymatic hydrolysis at pH 7.4 was about 10 times higher than the rate constant
      of the formation from MA in combination with cyclohexene oxide (k=8.3 versus 0.83
      micromol/l min), indicating an instability and thus a high reactivity of 2,3-EMA.
      The formation of the MA intermediate 2,3-EMA was not observed when heat
      inactivated liver microsomes were used (controls). SIGNIFICANCE: It could be
      clearly demonstrated that 2,3-EMA is a product of dental material metabolisms in
      biological systems. Therefore, increased toxicity might occur on dental
      restorative materials which are able to release (co)monomers which can be
      metabolized to MA.

PMID- 16458350
TI  - Crumb rubber filtration: a potential technology for ballast water treatment.
AB  - The removal of turbidity, particles, phytoplankton and zooplankton in water by
      crumb rubber filtration was investigated. A substantial reduction was achieved.
      Of the three variables, filter depth, media size and filtration rate, media size
      had the most significant influence. Smaller media size favored higher removal
      efficiency of all targeted matter. There was no apparent relationship between
      removal efficiency and filter depth. Higher filtration rate resulted in lower
      removal efficiency and higher head loss. Compared with conventional granular
      media filters, crumb rubber filters required less backwash, and developed lower
      head loss. Consequently crumb rubber filters could be run for a longer time or
      allow a higher filtration rate. The results also indicate that the crumb rubber
      filtration alone did not achieve the target removal of invasive species. However,
      crumb rubber filtration could potentially be used as a primary treatment
      technology to enhance the efficiency of a secondary treatment process (e.g.,
      disinfection).

PMID- 16458351
TI  - Surface engineering approaches to micropattern surfaces for cell-based assays.
AB  - The ability to produce patterns of single or multiple cells through precise
      surface engineering of cell culture substrates has promoted the development of
      cellular bioassays that provide entirely new insights into the factors that
      control cell adhesion to material surfaces, cell proliferation, differentiation
      and molecular signaling pathways. The ability to control shape and spreading of
      attached cells and cell-cell contacts through the form and dimension of the cell
      adhesive patches with high precision is important. Commitment of stem cells to
      different specific lineages depends strongly on cell shape, implying that
      controlled microenvironments through engineered surfaces may not only be a
      valuable approach towards fundamental cell-biological studies, but also of great
      importance for the design of cell culture substrates for tissue engineering.
      Furthermore, cell patterning is an important tool for organizing cells on
      transducers for cell-based sensing and cell-based drug discovery concepts. From a
      material engineering standpoint, patterning approaches have greatly profited by
      combining microfabrication technologies, such as photolithography, with
      biochemical functionalization to present to the cells biological cues in
      spatially controlled regions where the background is rendered non-adhesive ("non
      fouling") by suitable chemical modification. The focus of this review is on the
      surface engineering aspects of biologically motivated micropatterning of two
      dimensional (flat) surfaces with the aim to provide an introductory overview and
      critical assessment of the many techniques described in the literature. In
      particular, the importance of non-fouling surface chemistries, the combination of
      hard and soft lithography with molecular assembly techniques as well as a number
      of less well known, but useful patterning approaches, including direct cell
      writing, are discussed.

PMID- 16458352
TI  - Bone-like tissue formation using an equine COLLOSS E-filled titanium scaffolding
      material.
AB  - COLLOSS, a bovine extracellular matrix product containing native BMPs has already
      shown osteoinductive properties. To overcome problems with risk of transmissable
      spongiform encephalopathy (TSE) infection, an equine derived version was
      investigated in this study, named COLLOSS E. Disc- and tube-shaped implants were
      made from titanium fibre mesh. The central space of tubes was filled and the
      discs were impregnated with the COLLOSS E material to assess osteo-induction.
      These implants and non-loaded controls were implanted subcutaneously into the
      back of Wistar rats. After implantation periods of 2, 8, and 12 weeks, the
      implants were retrieved and sections were made. Histology showed a thin fibrous
      capsule surrounding the titanium mesh and a very mild tissue reaction. The disc
      implants, loaded or non-loaded, showed no bone formation at all. After 2 weeks of
      implantation 3 out of 5 of the loaded tubes showed bone formation with a mean of
      0.3 mm2 areas of new formed bone, after 8 weeks 3 out of 6 and 0.7 mm2, and after
      12 weeks this increased to 6 out of 6 and 1.0 mm2. In the non-loaded tubes only
      connective tissue in growth was seen. In conclusion, it was demonstrated that
      COLLOSS E material, loaded in a titanium fibre mesh tube shows osteoinductive
      properties. The effect of COLLOSS E has to be investigated further in orthotopic
      sites, which resemble more the final clinical application for bone
      reconstruction.

PMID- 16458353
TI  - Marinobufagenin impairs first trimester cytotrophoblast differentiation.
AB  - Preeclampsia is a pregnancy-specific syndrome that is the leading cause of
      maternal death during pregnancy in the developed world. In preeclampsia, a
      combination of immunological, genetic and environmental factors can lead to
      altered cytotrophoblast (CTB) invasion of the uterine wall, a process that is
      critical for normal placental development and pregnancy maintenance.
      Marinobufagenin (MBG) is an endogenous inhibitor of the sodium pump Na(+)/K(+)
      ATPase, and increased plasma MBG is associated with hypertension, chronic renal
      failure and preeclampsia. In the present study, the effects of MBG on CTB
      differentiation and invasion were investigated utilizing the first trimester
      extravillous CTB cell line SGHPL-4. MBG significantly inhibited SGHPL-4
      proliferation in a dose-dependent manner. In addition, growth factor-induced
      migration and invasion were significantly inhibited by MBG treatment. These
      findings demonstrate that MBG impairs CTB differentiation along the invasive
      pathway. Elucidating the mechanisms by which MBG impairs placental development
      may increase our understanding of fetal and maternal pathologies associated with
      preeclampsia.

PMID- 16458355
TI  - Ganoderma lucidum in cancer research.

PMID- 16458354
TI  - The suppressor domain of inositol 1,4,5-trisphosphate receptor plays an essential
      role in the protection against apoptosis.
AB  - The N-terminal 1-225 amino acids (aa) of the type 1 inositol 1,4,5-trisphosphate
      receptor (IP(3)R1) function as a suppressor/coupling domain. In this study we
      used IP(3)R-deficient B-lymphocytes to investigate the effects of modifications
      in this domain on IP(3) binding and Ca(2+)-release activity. Although the N
      terminal 1-225 aa of IP(3)R3 had the same role as in IP(3)R1, the suppression of
      IP(3) binding for IP(3)R1 was lost when the suppressor/coupling domains were
      exchanged between the two isoforms. Resulting chimeric receptors showed a higher
      sensitivity to IP(3)-induced activation (IICR). Deletion of 11 aa in IP(3)R1
      ([Delta76-86]-IP(3)R1) or replacing aa 76-86 of the IP(3)R1 in the
      suppressor/coupling domain by 13 aa of IP(3)R3 ([75-87 T3]-IP(3)R1) also resulted
      in increased IP(3) binding and sensitivity of IICR. These residues constitute the
      only part of the suppressor/coupling domain that is strikingly different between
      the two isoforms. Expression of [Delta76-86]-IP(3)R1 and of [75-87 T3]-IP(3)R1
      increased the propensity of cells to undergo staurosporine-induced apoptosis, but
      had no effect on the Ca(2+) content in the endoplasmic reticulum. In the cell
      model used, our observations suggest that the sensitivity of the Ca(2+)-release
      activity of IP(3)R1 to IP(3) influences the sensitivity of the cells to apoptotic
      stimuli and that the suppressor/coupling domain may have an anti-apoptotic
      function by attenuating the sensitivity of IICR.

PMID- 16458356
TI  - Facing mortality: a qualitative in-depth interview study on illness perception,
      lay theories and coping strategies of adult patients with acute leukemia 1 week
      after diagnosis.
AB  - In patients with acute leukemia we investigated the illness perceptions, lay
      theories and coping strategies 1 week after diagnosis. Semi-structured in-depth
      interviews were conducted with 12 patients. The transcribed interviews were
      analyzed by methods of qualitative research. Dramatic narrations of overwhelming
      threat in younger patients contrast to rationalization in elderly patients.
      Feelings of helplessness and efforts of normalization become apparent. Intense
      descriptions of physical injury due to invasive procedures allow verbalizing the
      fear of the disease. While coping strategies are complex, the overall importance
      of trust is recognized. Mortal fears are indirectly indicated. The results have
      consequences for psycho-oncological training and patient education.

PMID- 16458357
TI  - The current status of sheep pox disease.
AB  - Sheep are the moving banks of shepherds and their economic contribution in terms
      of meat, wool and skin/hide is immense. Various infectious diseases jeopardize
      the optimum productivity; among which sheep pox is more important as the disease
      restricts the export of sheep and their products besides other economic losses.
      Although, clinical signs are indicative of the disease but a laboratory
      confirmation is necessary for unequivocal diagnosis and studying epidemiology.
      The causative agent, sheep pox virus (SPV), is antigenically and genetically
      closely related to goat pox virus (GPV) and lumpy skin disease virus (LSDV), the
      other members of the genus capripox virus. In some countries, SPV and GPV are
      cross infective to small ruminants posing problem in diagnosis and epidemiology.
      However, recent studies have showed that the viruses are phylogenetically
      distinct and can be differentiated by molecular tools. Prophylaxis using
      attenuated vaccines is the choice of control measure as the immunity is long
      lasting. Detailed information on isolation, identification, pathology,
      epidemiology, diagnosis and prophylaxis would not only help in updating the
      knowledge of scientific fraternity but will be useful to the policy makers in
      order to formulate appropriate measures for control and eradication of the
      disease. This synthesis is to present an up-to-date review of the disease and its
      control to provide the reader with an overview of the problem.

PMID- 16458358
TI  - Nonheme iron(II) complexes of macrocyclic ligands in the generation of
      oxoiron(IV) complexes and the catalytic epoxidation of olefins.
AB  - Mononuclear nonheme oxoiron(IV) complexes bearing 15-membered macrocyclic ligands
      were generated from the reactions of their corresponding iron(II) complexes and
      iodosylbenzene (PhIO) in CH(3)CN. The oxoiron(IV) species were characterized with
      various spectroscopic techniques such as UV-vis spectrophotometer, electron
      paramagnetic resonance, electrospray ionization mass spectrometer, and resonance
      Raman spectroscopy. The oxoiron(IV) complexes were inactive in olefin
      epoxidation. In contrast, when iron(II) or oxoiron(IV) complexes were combined
      with PhIO in the presence of olefins, high yields of epoxide products were
      obtained. These results indicate that in addition to the oxoiron(IV) species,
      there must be at least one more active oxidant (e.g., Fe(IV)-OIPh adduct or
      oxoiron(V) species) that effects the olefin epoxidation. We have also
      demonstrated that the ligand environment of iron catalysts is an important factor
      in controlling the catalytic activity as well as the product selectivity in the
      epoxidation of olefins by PhIO.

PMID- 16458359
TI  - Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are inflammatory lung
      diseases that are characterized by systemic and chronic localized inflammation
      and oxidative stress. Sources of oxidative stress arise from the increased burden
      of inhaled oxidants, as well as elevated amounts of reactive oxygen species (ROS)
      released from inflammatory cells. Increased levels of ROS, either directly or via
      the formation of lipid peroxidation products, may play a role in enhancing the
      inflammatory response in both asthma and COPD. Moreover, in COPD it is now
      recognized as the main pathogenic factor for driving disease progression and
      increasing severity. ROS and lipid peroxidation products can influence the
      inflammatory response at many levels through its impact on signal transduction
      mechanisms, activation of redox-sensitive transcriptions factors, and chromatin
      regulation resulting in pro-inflammatory gene expression. It is this impact of
      ROS on chromatin regulation by reducing the activity of the transcriptional co
      repressor, histone deacetylase-2 (HDAC-2), that leads to the poor efficacy of
      corticosteroids in COPD, severe asthma, and smoking asthmatics. Thus, the
      presence of oxidative stress has important consequences for the pathogenesis,
      severity, and treatment of asthma and COPD. However, for ROS to have such an
      impact, it must first overcome a variety of antioxidant defenses. It is likely,
      therefore, that a combination of antioxidants may be effective in the treatment
      of asthma and COPD. Various approaches to enhance the lung antioxidant screen and
      clinical trials of antioxidant compounds are discussed.

PMID- 16458360
TI  - Thermodynamic stability and formation of aggregates of human immunoglobulin G
      characterised by differential scanning calorimetry and dynamic light scattering.
AB  - The final process step of polyclonal human immunoglobulin G is formulation with
      agents such as sugars, polyols, amino acid and salts. Often the most stable
      formulations were empirically identified. Physicochemical methods, such as
      differential scanning calorimetry and dynamic light scattering, provide a deeper
      insight on the biophysical properties of such a protein solution. The combination
      of these methods proved to be sensitive enough to detect fine differences in the
      properties relevant for the development of stable protein solutions. The
      influence of additives, such as maltose and glycine in combination with water or
      low concentrations of salts, on human immunoglobulin preparations was analysed.
      Differential scanning calorimetry illustrated that 0.2 M glycine had better
      stabilising effects compared to 10% maltose. Dynamic light scattering and
      differential scanning calorimetry revealed that solutions preventing aggregation
      were not optimal in terms of thermodynamic stability. Aggregation was minimised
      with increasing ionic strength, shown by dynamic light scattering, whereas
      thermodynamic stability for heat sensitive parts of human immunoglobulin G,
      analysed with differential scanning calorimetry, was decreased.

PMID- 16458361
TI  - Ultrafast random-access scanning in two-photon microscopy using acousto-optic
      deflectors.
AB  - Two-photon scanning microscopy (TPSM) is a powerful tool for imaging deep inside
      living tissues with sub-cellular resolution. The temporal resolution of TPSM is
      however strongly limited by the galvanometric mirrors used to steer the laser
      beam. Fast physiological events can therefore only be followed by scanning
      repeatedly a single line within the field of view. Because acousto-optic
      deflectors (AODs) are non-mechanical devices, they allow access at any point
      within the field of view on a microsecond time scale and are therefore excellent
      candidates to improve the temporal resolution of TPSM. However, the use of AOD
      based scanners with femtosecond pulses raises several technical difficulties. In
      this paper, we describe an all-digital TPSM setup based on two crossed AODs. It
      includes in particular an acousto-optic modulator (AOM) placed at 45 degrees with
      respect to the AODs to pre-compensate for the large spatial distortions of
      femtosecond pulses occurring in the AODs, in order to optimize the spatial
      resolution and the fluorescence excitation. Our setup allows recording from
      freely selectable point-of-interest at high speed (1kHz). By maximizing the time
      spent on points of interest, random-access TPSM (RA-TPSM) constitutes a promising
      method for multiunit recordings with millisecond resolution in biological
      tissues.

PMID- 16458362
TI  - High frequency oscillations in the somatosensory evoked potentials (SSEP's) are
      mainly due to phase-resetting phenomena.
AB  - A small series of high frequency oscillations (HFOs) overlapping the earliest
      part of the N20 wave can be observed in the somatosensory evoked potentials
      (SSEPs) of normal subjects. We tried to elucidate whether these high frequency
      components are mainly due to phase-resetting phenomena, to the emergence of new
      oscillations related to the stimuli, or to a combination of both. Averaged median
      nerve SSEPs from seven healthy subjects were studied by means of time-frequency
      analysis. The presence of new oscillatory activities was evaluated by averaging
      the energy of the single-trial time-frequency transforms in the HFOs range (400
      1000 Hz). To study phase-resetting phenomena, we measured inter-trial coherence
      (ITC) in the same frequency range. A marked inter-trial coherence related to the
      HFOs was found, whereas energy changes (related to the emergence of new
      oscillations) were minimal. The combination of these three different approaches
      suggests that the HFOs are mainly due to resettings of the ongoing EEG activity
      originated in response to the stimuli. The emergence of new activities does not
      seem to be a relevant mechanism in the formation of these components.

PMID- 16458364
TI  - The close link between suicide attempts and mixed (bipolar) depression:
      implications for suicide prevention.
AB  - BACKGROUND: Previous reports have shown a significant relationship between
      suicide ideation and mixed depression. The aim of this study was to explore the
      prevalence and clinical characteristics of mixed depression among non-violent
      suicide attempters. METHODS: Using a structured interview (modified Mini
      International Neuropsychiatric Interview) and assessing all the symptoms of 16
      psychiatric diagnoses, the authors examined 100 consecutive nonviolent suicide
      attempters (aged 18-65) within 24 h after their attempts. Mixed depression was
      defined as a major depressive episode (MDE)/dysthymic disorder plus 3 or more co
      occurring hypomanic symptoms, according to the definition validated by Akiskal
      and Benazzi [Akiskal, H.S., Benazzi, F., 2003a. Delineating depressive mixed
      states: Their therapeutic significance. Clin. Approaches Bipolar Disord. 2, 41
      47, Akiskal, H.S., Benazzi, F., 2003b. Family history validation of the bipolar
      nature of depressive mixed states. J. Affect. Disord. 73, 113-122.]. RESULTS:
      Current mixed depression was present in 63.0% in the total sample, and in 70.8%
      among the 89 depressive suicide attempters. Irritability, distractibility and
      psychomotor agitation were present in more than 90% of the subjects with mixed
      depression. The rate of mixed depression was significantly higher among bipolar
      than non-bipolar depressive suicide attempters (90% vs. 62%). Patients with mixed
      depression had the following concurrent disorders: bipolar disorders 41.0%, panic
      disorder 30.0%, generalized anxiety disorder 89.0%, alcohol abuse/dependence
      56.0%, and substance abuse 27.0%. Mixed depression versus non-mixed depression
      had the following significant associations (odds ratio=OR): females 2.4, bipolar
      II disorder 9.3, generalized anxiety disorder 41.3, irritability 101.6 and
      psychomotor agitation 61.1. LIMITATIONS: The study didn't include suicide
      attempters with very high risk of fatality. CONCLUSIONS: The important new
      finding of this study is the very high prevalence of mixed depression among
      depressed suicide attempters. The rates of mixed depression among bipolar and non
      bipolar depressive suicide attempters were much higher than previously reported
      among nonsuicidal bipolar II and unipolar depressive outpatients, suggesting that
      suicide attempters come mainly from mixed depressives with predominantly bipolar
      II base. Irritability and psychomotor agitation were the strongest predictors of
      suicide attempt. From a public health standpoint, our data highlight the
      necessity of detecting and treating mixed (bipolar) depression in the prevention
      of suicidal behaviour.

PMID- 16458363
TI  - Neurocognitive dysfunction in antidepressant-free, non-elderly patients with
      unipolar depression: alerting and covert orienting of visuospatial attention.
AB  - BACKGROUND: Cognition is impaired across various domains in young and middle-age
      adults with unipolar depression. Performance appears in general worse in
      effortful tasks requiring executive function and attention. Probing specific
      cognitive operations in depressed patients, such as alerting and covert orienting
      of visuospatial attention, can better define and characterize the
      pathophysiology. METHODS: Nine antidepressant-free, clinically depressed patients
      and fourteen age-matched healthy subjects performed a Posner task with components
      of phasic alerting and covert orienting of visuospatial attention. Reaction times
      were analyzed by repeated-measures ANOVA with DIAGNOSIS as the between-group
      measure. Visual field (FIELD), stimulus onset asynchrony (SOA), and orienting CUE
      condition were within-subject, repeated measures. RESULTS: ANOVA showed intact
      attentional orienting in both groups. There were no FIELD differences across
      groups nor main effects of DIAGNOSIS. Interactions of DIAGNOSIS with SOA and
      DIAGNOSIS with CUE condition identified a phasic alerting deficit in the
      depressed patients. There were no significant effects of time-on-task, suggesting
      adequate vigilance or sustained attention in both groups. Plotting depressed
      versus control subjects' reaction time for each task condition (Brinley plot)
      showed linearity with a slope of 1.6 (i.e., patients were 1.6-fold slower) and a
      correlation coefficient of 0.98 (accounting for 96% of the overall variance).
      LIMITATIONS: This study contains a small sample with potential for Type II error.
      The study addressed depression at the syndrome level. Depressed patients selected
      on particular symptom dimensions (e.g., anxiety, psychomotor retardation, etc.)
      could reveal abnormalities in hemisphere asymmetries that were not observed here.
      CONCLUSIONS: These data highlight that global slowing is a major cognitive
      deficit in depression and arises across levels of difficulty. Putative specific
      deficits in depression need adjustment for the large effects of global slowing
      which can mimic selective impairments in more effortful task conditions.

PMID- 16458365
TI  - Seasonality of mood disorders in adults with lifetime attention
      deficit/hyperactivity disorder (ADHD).
AB  - BACKGROUND: The objective of this study was to estimate the prevalence of
      Seasonal Affective Disorder (SAD) in adults with lifetime Attention
      Deficit/Hyperactivity Disorder (ADHD). METHOD: Patients eligible for this study
      had lifetime impairing symptoms of ADHD and a current and/or past co-morbid mood
      disorder according to their medical record. The Seasonal Pattern Assessment
      Questionnaire (SPAQ) was administered by a telephone interview to assess
      seasonality. RESULTS: The overall rate of SAD in this clinical population of
      adults with ADHD was estimated at 27%. Females were more at risk to develop SAD
      than men. LIMITATIONS: The SPAQ is a screening, not a diagnostic instrument.
      CONCLUSIONS: SAD symptoms are frequently comorbid with ADHD in adults. These
      results have clinical relevance for the recognition and treatment of SAD with
      bright light therapy in adults with ADHD.

PMID- 16458366
TI  - Positive and negative affect within the realm of depression, stress and fatigue:
      the two-factor distress model of the Global Mood Scale (GMS).
AB  - BACKGROUND: The Global Mood Scale (GMS; [Denollet, J., 1993a. Emotional distress
      and fatigue in coronary heart disease: the Global Mood Scale (GMS). Psychol Med
      23, 111-121., Denollet, J., 1993b. The sensitivity of outcome assessment in
      cardiac rehabilitation. J Consult Clin Psychol 61, 686-695.]) was originally
      developed as a measure of positive affect (PA) and negative affect (NA) in
      cardiac patients. The purpose of this study was to examine its two-factor affect
      model in the realm of stress, depression, and fatigue in working adults. METHODS:
      Affect, stress, depression, and fatigue were assessed with validated
      questionnaires in a sample of 228 adults (49.6% male; mean = 41.4 +/- 9 years)
      from the working population. RESULTS: The GMS PA and NA scales were internally
      consistent (Cronbach's alpha = .94 and alpha = .93, respectively), and correlated
      in the expected direction with their corresponding mood scales from the Positive
      and Negative Affect Schedule (PANAS). Factor analyses of the 40 mood terms
      comprising the GMS and PANAS yielded one common PA-dimension, but two NA
      dimensions reflecting emotional exhaustion (GMS) and anxious apprehension (PANAS)
      as different components of the stress process. A relatively high mean NA score of
      the GMS suggested that these working adults perceived terms that refer to
      malaise/deactivation as being relevant to describe their negative affective
      status. The GSM-NA scale was related to stress, depression and fatigue while the
      GMS-PA scale was positively associated with quality of life. LIMITATIONS: This
      study is based on a cross-sectional design. CONCLUSIONS: The association between
      the PA (negative correlation) and NA (positive correlation) scales of the GMS and
      perceived stress, depressive symptoms, and fatigue supports the validity of its
      two-factor model. Assessment of both PA and NA may benefit a better understanding
      of emotional distress in adults from the working population.

PMID- 16458367
TI  - Mood variability in anxiety disorders.
AB  - BACKGROUND: To investigate whether patients with anxiety disorders have more
      variable mood than control subjects. METHODS: Twenty-eight patients with anxiety
      disorders and 28 controls were assessed with the State-Trait Anxiety Inventory
      Trait form (STAIT), Beck Depression Inventory (BDI), Mood Disorder Questionnaire
      (MDQ), and TEMPS-A questionnaire for temperament. Participants used Visual
      Analogue Scales (VAS) to rate low, high and anxious moods, morning and evening,
      for 7 consecutive days. Mood variability was calculated with the Mean Square
      Successive Difference (MSSD) and the Standard Error of the Mean (SEM), both
      derived from the VAS ratings. RESULTS: (1) The MSSD and SEM measures for low mood
      and anxiety variability were higher in patients than controls. The SEM for high
      mood was marginally higher in patients. (2) The high mood measures separated into
      two clusters: (a) the mean of the VAS high mood scale and the TEMPS hyperthymia
      scale apparently measure an adaptive high mood or hyperthymia that did not
      correlate or correlated negatively with depression (BDI). (b) The MSSD of the VAS
      high mood scale, the TEMPS cyclothymia scale, and the MDQ correlated with each
      other and with the BDI as variable high mood that is distressing. LIMITATIONS:
      Small sample size. CONCLUSIONS: Patients with anxiety disorders show more mood
      variability than controls. We also found a difference in the measures of adaptive
      high mood from variable high mood, the latter associated with depression. Mood
      variability is an important but neglected aspect of distress in patients with
      anxiety disorders.

PMID- 16458368
TI  - Humoral immunity and correlation between ELISA, hemagglutination inhibition, and
      neutralization tests after vaccination against tick-borne encephalitis virus in
      children.
AB  - Vaccination against tick-borne encephalitis (TBE) virus is the measure of choice
      for disease control in endemic areas, as no treatment is available. In Italy, the
      province of Belluno is one of the most active TBE virus infection foci. In this
      study sera were examined from vaccinated children living in areas around Belluno
      in order to monitor the immune response after anti-TBE vaccination. For the
      assessment of neutralizing antibodies, a plaque reduction neutralization test
      (PRNT) was optimized and the correlation between enzyme-linked immunosorbent
      assay (ELISA), hemaglutination inhibition (HI), and neutralizing antibodies
      titers was evaluated. All children had high serum levels of TBE IgG in ELISA test
      after the vaccination, in agreement with previous studies. HI and PRNT titers
      ranged between very low and high levels. A good correlation between HI and PRNT
      titers, and with IgG ELISA titers, was observed. PRNT is an useful assay for
      monitoring protective immunity after the completion of anti-TBE vaccination. This
      type-specific assay is an important tool for differential diagnosis in cases
      where the presence of cross-reactive antibodies due to other flavivirus
      infections or vaccinations cannot be excluded.

PMID- 16458369
TI  - Sleep in captive chimpanzee (Pan troglodytes): the effects of individual and
      environmental factors on sleep duration and quality.
AB  - Various abiotic and social factors are hypothesized to influence sleep in
      primates. Chimpanzee sleeping behavior has been examined only in a limited
      fashion, both in the wild and in captivity. Previous research, however limited,
      has suggested that chimpanzee sleep is non-dynamic. This study used an objective
      behavioral model of sleep as a framework in which to test the hypothesis that
      changes in individual (age and sex) and environmental (temperature and humidity)
      factors influence sleep patterns in 20 captive chimpanzees. The nocturnal
      behavior of the subjects was recorded continuously using video cameras equipped
      with enhanced nighttime visibility connected to time-lapse videocassette
      recorders. Chimpanzees in this study slept 8.81 h per night, close to the
      averages reported for both industrialized and traditional human societies (7-9h),
      as opposed to that of previous chimpanzee studies (11-12h). Also, the idea that
      chimpanzees sleep in one continuous period with little to no nocturnal awakenings
      was also refuted. Captive chimpanzee sleep behavior was, in fact, dynamic and
      complex with frequent awakenings. Older chimpanzees slept longer, had higher
      sleep quality, and shorter nighttime disturbances than prime adult chimpanzees.
      Finally, ambient temperature and humidity affected sleep duration and quality.
      The results of this study reveal that chimpanzee sleep behaviors are complicated
      interactions between both intrinsic and extrinsic factors.

PMID- 16458370
TI  - Bioaccumulation and toxicity of 4-nonylphenol (4-NP) and 4-(2-dodecyl)-benzene
      sulfonate (LAS) in Lumbriculus variegatus (Oligochaeta) and Chironomus riparius
      (Insecta).
AB  - The discharge of surfactants, such as 4-nonylphenol (4-NP) and linear
      alkylbenzene sulfonates (LAS), into water bodies leads to accumulation of the
      chemicals in the sediments and may thus pose a problem to benthic organisms. To
      study the bioaccumulation of surfactants, Oligochaeta worm Lumbriculus variegatus
      was exposed to sediment-spiked, [14C]-labeled 4-NP and 4-(2-dodecyl)-benzene
      sulfonate (C12-LAS) in three different sediments (S1-S3). The sediments were
      characterized for organic carbon (OC) content and particle size distribution. The
      acute toxicity was examined by exposing L. variegatus and three to four instar
      Chironomus riparius (Insecta) larvae in water-only exposure to 4-NP and LAS at
      different concentrations. After 48-h exposure, lethal water concentrations (LC50)
      and lethal body residues (LBR50) were estimated using liquid scintillation
      counting. Chronic toxicity was evaluated in two different sediments by exposing
      first instar C. riparius larvae to sediment-spiked chemicals at different
      concentrations. After 10 days, the sublethal effects of surfactants were observed
      by measuring wet weight and head capsule length. Finally, another 10-day test was
      set up in order to measure the LAS body residues associated with sublethal
      effects in C. riparius in S2 sediment. The bioaccumulation test revealed that the
      bioaccumulation of both 4-NP and LAS increased as the sediment organic matter
      content decreased. It is assumed that the chemical binding to organic material
      decreased chemical bioavailability. The acute toxicity tests showed that L.
      variegatus was more tolerant of 4-NP, and C. riparius was more tolerant of LAS
      when based on water exposure concentration. The LBR-estimates revealed, however,
      that L. variegatus tolerated clearly higher tissue residues of both chemicals
      compared with C. riparius. Both chemicals had sublethal effects on C. riparius
      growth in sediment exposure, reducing larvae wet weight and head capsule size. 4
      NP, however, showed an irregular dose-response pattern. The characteristics of
      the exposure media affected the bioaccumulation potential of both chemicals.
      Thus, exposure concentrations offered no prediction of body residue, and
      therefore it is proposed that organism body residue offered a more accurate dose
      metric for chemical exposure than the chemical concentration of the environment.

PMID- 16458371
TI  - Improved transfection and new selectable markers for the rodent malaria parasite
      Plasmodium yoelii.
AB  - The rodent malaria Plasmodium yoelii is a useful model to study protective
      immunity to pre-erythrocytic stages of infection, pathogenesis of erythrocytic
      stages, and vaccine development. However, the utility of the P. yoelii model
      system has not been fully realized because transfection and genetic manipulation
      methodologies for this rodent species are less developed than that of another
      rodent species Plasmodium berghei. Here we report improved transfection
      efficiency using the AMAXA nucleofector system compared to conventional
      transfection methodologies. We also show that heterologous promoters from P.
      berghei can be used to drive expression of a green fluorescent protein (GFP)
      reporter protein in P. yoelii. In an effort to develop additional selectable
      markers for this parasite, we also tested positive selectable markers that have
      been used successfully in P. falciparum and P. berghei. Human dihydrofolate
      reductase (hdhfr) and Toxoplasma gondii dihydrofolate reductase-thymidylate
      synthase (Tgdhfr-ts) conferred drug resistance to WR99210 and pyrimethamine,
      respectively, when introduced as episomes. These improvements should make genetic
      manipulation of P. yoelii more amenable and facilitate further studies of host
      parasite interactions using this attractive rodent model.

PMID- 16458372
TI  - Specific expression of galanin in the peri-infarct zone after permanent focal
      cerebral ischemia in the rat.
AB  - Galanin (Gal) is a neuropeptide with supposed neurotrophic-like action. In the
      present study, expression of Gal has been investigated in the core and peri
      infarct zone at 1, 4, 24 and 72 h after middle cerebral artery occlusion (MCAo)
      in the rat. Three days after MCAo a small but consistent number of morphological
      intact Gal-positive neuronal cells were observed in the peri-infarct zone. Gal
      positive cells were barely detectable in the infarct and peri-infarct zone at 24
      h. No Gal immunopositive cells were detected in brain subjected to 1 and 4 h of
      ischemia. Gal immunoreactivity was also detected in myelinated fibers 4 and 24 h
      after focal ischemia. Gal may be a peptide with neurotrophic and plasticity
      functions under stress conditions.

PMID- 16458373
TI  - GSH depletion, protein S-glutathionylation and mitochondrial transmembrane
      potential hyperpolarization are early events in initiation of cell death induced
      by a mixture of isothiazolinones in HL60 cells.
AB  - We recently described that brief exposure of HL60 cells to a mixture of 5-chloro
      2-methyl-4-isothiazolin-3-one (CMI) and 2-methyl-4-isothiazolin-3-one (MI)
      induces apoptosis at low concentrations (0.001-0.01%) and necrosis at higher
      concentrations (0.05-0.1%). In this study, we show that glutathione (GSH)
      depletion, reactive oxygen species generation, hyperpolarization of mitochondrial
      transmembrane potential (DeltaPsim) and formation of protein-GSH mixed
      disulphides (S-glutathionylation) are early molecular events that precede the
      induction of cell death by CMI/MI. When the cells exhibit common signs of
      apoptosis, they show activation of caspase-9, reduction of DeltaPsim and, more
      importantly, decreased protein S-glutathionylation. In contrast, necrosis is
      associated with severe mitochondrial damage and maximal protein S
      glutathionylation. CMI/MI-induced cytotoxicity is also accompanied by decreased
      activity of GSH-related enzymes. Pre-incubation with L-buthionine-(S,R)
      sulfoximine (BSO) clearly switches the mode of cell death from apoptosis to
      necrosis at 0.01% CMI/MI. Collectively, these results demonstrate that CMI/MI
      alters the redox status of HL60 cells, and the extent and kinetics of GSH
      depletion and S-glutathionylation appear to determine whether cells undergo
      apoptosis or necrosis. We hypothesize that S-glutathionylation of certain thiol
      groups accompanied by GSH depletion plays a critical role in the molecular
      mechanism of CMI/MI cytotoxicity.

PMID- 16458374
TI  - A dynamic model of supply of elective surgery in the presence of waiting times
      and waiting lists.
AB  - This paper analyses hospitals' decisions regarding the supply of elective surgery
      in a dynamic model in the presence of waiting times and waiting lists. We show
      that periods of increasing (decreasing) supply and increasing (decreasing)
      waiting list may be optimal paths towards the steady state. We also analyse the
      hospitals' response to exogenous shocks on the demand and the supply. For
      example, an increase in the marginal tariff for the provider generates
      overshooting in the supply: supply jumps upwards when the shock is introduced and
      then slowly reduces towards the steady-state value.

PMID- 16458375
TI  - Comparison of molecular techniques for the typing of Mycoplasma hyopneumoniae
      isolates.
AB  - In this study, we compared the potential of amplified fragment length
      polymorphism (AFLP), random amplified polymorphic DNA (RAPD) analysis,
      restriction fragment length polymorphism (RFLP) of the gene encoding lipoprotein
      P146, and the variable number of tandem repeats (VNTR) of the P97 encoding gene,
      as possible methods for typing an international collection of Mycoplasma
      hyopneumoniae isolates. All techniques showed a typeability of 100% and high
      intraspecific diversity. However, the discriminatory power of the different
      techniques varied considerably. AFLP (>0.99) and PCR-RFLP of the P146 encoding
      gene (>0.98) were more discriminatory than RAPD (0.95) and estimation of the VNTR
      of P97 (<0.92). Other, preferentially well spread, tandem repeat regions should
      be included in order for this latter technique to become valuable for typing
      purposes. RAPD was also found to be a less interesting typing technique because
      of its low reproducibility between different runs. Nevertheless, all molecular
      techniques showed overall more resemblance between strains isolated from
      different pigs from the same herd. On the other hand, none of the techniques was
      able to show a clear relationship between the country of origin and the
      fingerprints obtained. We conclude that AFLP and an earlier described PFGE
      technique are highly reliable and discriminatory typing techniques for outlining
      the genomic diversity of M. hyopneumoniae isolates. Our data also show that RFLP
      of a highly variable gene encoding P146 may be an equally useful alternative for
      demonstrating intraspecific variability, although the generation of sequence
      variability of the gene remains unclear and must be further examined.

PMID- 16458376
TI  - Intermovement interval and spatial assimilation effects in sequential bimanual
      and unimanual movements.
AB  - This study extended earlier work by showing spatial assimilations in sequential
      bimanual and unimanual movements separated by 1.5-3.5 s. In Experiments 1 and 2,
      30 right-handed participants (18-22 years of age) made rapid single and bimanual
      lever reversals of 20 degrees and 60 degrees assigned to 1.5, 2.5, or 3.5 s
      intermovement interval groups. Participants self-timed the intermovement interval
      in the first experiment, but it was provided in the second experiment using
      separate auditory stimuli. In the third experiment, participants performed both
      the 20 degree and 60 degree movement with the same hand. In all experiments, the
      shorter-distance limb overshot and the longer-distance limb undershot the targets
      in both bimanual and unimanual sequential movements relative to single movements
      in all three intermovement interval groups, particularly in the non-dominant left
      limb. The results suggest that assimilation effects in sequential movements are
      caused by command interactions at the planning level, but the effects are reduced
      by practice.

PMID- 16458377
TI  - Postural fluctuations during pointing from a unilateral or bilateral stance.
AB  - An experiment was conducted to compare the effects of bilateral and unilateral
      stance on postural fluctuations and intralimb coordination during active balance
      control. Fifteen participants stood bilaterally and unilaterally while conducting
      a pointing task with an outstretched arm. Excursion of center of foot pressure
      (CoP) and limb movements were recorded with a force plate and eight dual-axis
      accelerometers, respectively. Compared to bilateral stance, unilateral stance
      resulted in wider CoP trajectories and greater postural fluctuations, especially
      in the lower limbs. The limb-dependent postural fluctuations during unilateral
      stance were associated with an increased coupling between the upper limb segments
      and a decreased coupling between the segments of the stance leg. Unilateral
      stance further resulted in greater regularity and spectral changes in postural
      fluctuations of the trunk and lower limb due to increased central oscillations (8
      15 Hz). The observed structural differences in postural fluctuations between
      unilateral and bilateral stance strongly suggested that the postural control
      system modulates joint stiffness in a stance-dependent manner. Probably, in
      unilateral stance, attentive control was shifted to the stance leg at the expense
      of increasing arm stiffness to reduce movement redundancy.

PMID- 16458378
TI  - Human bilateral deficit during a dynamic multi-joint leg press movement.
AB  - Bilateral deficit has been used to describe the phenomenon of a reduction in
      performance during synchronous bilateral movements when compared to the sum of
      identical unilateral movements. The study of bilateral deficit in humans under
      isometric, and to a lesser extent, dynamic conditions has shown bilateral
      decreases in force and muscle activation, and delayed reaction time. Results are
      equivocal, however, and biomechanical analyses of dynamic conditions, i.e.,
      movements, are lacking. Our purpose was to determine, through an analysis of
      kinematic, kinetic, and electromyographic (EMG) data, whether or not bilateral
      deficit was present during a dynamic multi-joint movement under conditions where
      the external load was relatively equal for unilateral and bilateral efforts. Five
      male participants performed repeated unilateral and bilateral maximal horizontal
      leg press jumps under 100% (1BW) and 200% (2BW) relative body weight loads.
      Significant bilateral deficits in resultant ground reaction impulse of 27.7% and
      13.0% were present in 1BW and 2BW, respectively. Maximum joint power at the hip
      exhibited significant deficits in both 1BW and 2BW of 35.6% and 25.1%,
      respectively. In both 1BW and 2BW conditions, ankle (15.5% and 11.5%), knee
      (10.9% and 5.7%), and hip (38.5% and 30.4%) work was significantly affected.
      Statistically significant EMG bilateral deficits were found in every muscle in
      both conditions except for rectus femoris during the 2BW trials. Bilateral
      deficit values ranged from 9.1% to 20.9% for 1BW, while deficits between 6.1% and
      20.7% were found in 2BW. These results indicate that during dynamic leg press,
      bilateral deficit does exist, but that individual muscle activation levels and
      joint kinetics are not equally affected.

PMID- 16458379
TI  - Comparison and evaluation of two common methods to measure center of mass
      displacement in three dimensions during gait.
AB  - Center of mass displacement during gait has frequently been used as an indicator
      of gait efficiency or as a complement to standard gait analysis. With
      technological advances, measuring the center of mass as the centroid of a multi
      segment system is practical and feasible, but must first be compared to the well
      established Newtonian computation of double-integrating the ground reaction
      force. This study aims to verify that the kinematic centroid obtained from a
      commonly-used model (Vicon Peak Plug-In-Gait) provides at least as reliable
      measurements of center of mass displacement as those obtained from the ground
      reaction forces. Gait data was collected for able-bodied children and children
      with myelomeningocele who use larger lateral center of mass excursions during
      gait. Reasonable agreement between methods was found in fore-aft and vertical
      directions, where the methods' excursions differed by an average of less than 10
      mm in either direction, and the average RMS differences between methods' computed
      curves were 6 and 13 mm. Particularly good agreement was observed in the lateral
      direction, where the calculated excursions differed by an average of less than 2
      mm and the RMS difference was 5 mm. Error analyses in computing the center of
      mass displacement from ground reaction forces were performed. A 5% deviation in
      mass estimation increased the computed vertical excursion twofold, and a 5%
      deviation in the integration constant of initial velocity increased the computed
      fore-aft excursions by 10%. The suitability of calculating center of mass
      displacement using ground reaction forces in a patient population is questioned.
      The kinematic centroid is susceptible to errors in segment parameters and marker
      placement, but results in plausible results that are at least within the range of
      doubt of the better-established ground reaction force integration, and are more
      useful when interpreting 3-D gait data.

PMID- 16458380
TI  - Modelling the parallel bars in men's artistic gymnastics.
AB  - The modelling of the parallel bars-gymnast system is considered. A 2D frontal
      plane model for the parallel bars apparatus is developed, enabling technique and
      injury analysis to be undertaken when combined with an interacting gymnast body
      model. We also demonstrate how such a gymnast body model may be combined with the
      parallel bars model by use of a simplifying symmetry consideration about the
      gymnast's sagittal plane. This symmetry consideration implies that just half the
      gymnast body and one of the two bars, are needed in the total model. We found
      that midpoint vertical parallel bars dynamics may be modelled by three
      parameters, using a single damped spring-mass model with linear force
      displacement characteristics. Horizontally, as opposed to the vertical direction,
      bar endpoints accounted for a substantial part (35%) of the midpoint movement,
      demanding two serially connected springs for this direction. One spring
      represented the absolute horizontal movement of the bar endpoints, while the
      other spring represented the superimposed horizontal movement of bar midpoint
      relative to the endpoints. Both horizontal springs had the same characteristics
      as the vertical spring, giving a total of nine parameters for the three-spring
      bar model. Bar parameters were estimated by fitting the modelled bar movements to
      corresponding measured movements caused by a 140 kg lateral pendulum below the
      bar midpoint. Validation was then undertaken by comparing model-predicted bar
      movements to corresponding measurements using lateral pendulums of 100 kg and 60
      kg, respectively. Finally, a gymnast handstand position was modelled and used to
      compare model-predicted and measured bar oscillations following a somersault
      backwards to a handstand position. The model gave convincing predictions of bar
      movements both for the 100 kg (1 period, RMS error of 7.0 mm) and 60 kg (1
      period, RMS error of 3.7 mm) pendulums, as well as for the somersault landing (2
      periods, RMS error of 8.1 mm).

PMID- 16458381
TI  - Movement analysis in the early detection of newborns at risk for developing
      spasticity due to infantile cerebral palsy.
AB  - In order to limit the consequences of infantile cerebral palsy (ICP),
      physiotherapy should start as early as possible. This requires that infants at
      risk are detected at the earliest age possible. Today, diagnosis is based on
      visual observation by physicians and as such is influenced by subjective
      impressions. Objective methods, quantifying the pathological deviation from
      normal spontaneous motor activity would be preferable as they, for example, allow
      an inter- and intra-individual comparison of movement. In this paper we have
      developed a methodology that allows the 3-dimensional acquisition of
      unconstrained movement in newborn babies, using a motion analysis system. From
      the recorded movement data we have extracted 53 quantitative parameters that
      describe the differences between healthy and affected participants. Considered
      individually, each of these parameters does not permit a conclusive statement to
      be made as to whether or not the patient is at risk. Cluster analysis based on
      Euclidian distances therefore has been used to find an optimal combination of
      eight parameters. The optimal combination has been subsequently applied to
      organize the participants' movement into preferably homogeneous classes labelled
      "healthy" or "at risk". Classification was performed utilising quadratic
      discriminant analysis. The methodology presented allows a reliable discrimination
      between healthy and affected participants. Overall detection rate reached 73%.
      This value is expected to rise with increasing patient and norm collective
      database size.

PMID- 16458382
TI  - The effects of unilateral grab rail assistance on the sit-to-stand performance of
      older aged adults.
AB  - This study investigated the effects of unilateral grab rail assistance during the
      sit-to-stand transfer to develop an understanding of lower limb joint mechanics
      and whole body movement patterns. External reaction forces at the grab rail and
      floor interfaces were also investigated to understand the nature of the
      assistance provided by the introduction of unilateral upper body assistance.
      While 12 older aged adults performed the sit-to-stand, three-dimensional body
      segment kinematics were recorded to determine lower body joint motion and whole
      body centre of mass motion. Grab rail reaction forces and bilateral ground
      reaction forces were recorded to determine external reaction forces and lower
      body joint kinetics. Grab rail assisted conditions were compared with unassisted
      transfers. During grab rail assistance, a systematic asymmetry was introduced to
      lower limb joint kinetics, without noticeable alterations to peak lower body
      joint motion and whole body movement patterns. Ipsilateral net joint moments and
      powers decreased in the ankle and hip and increased in the knee, while the
      contralateral net joint moments and powers increased in the hip and decreased in
      the knee. Joint kinetic and kinematic responses suggest a motor control strategy
      that maintains symmetric sit-to-stand movement patterns by adjusting bilateral
      muscle control when a unilateral external reaction force is provided.
      Understanding the mechanical assistance that is generated during the sit-to-stand
      will facilitate optimal design of grab rails for older aged adults and may
      contribute to design for specific pathologies. Such design implementation will
      influence the ability of older aged adults to remain independent in the
      community.

PMID- 16458383
TI  - Microglia/macrophages responses to kainate-induced injury in the rat retina.
AB  - The present study was aimed to elucidate how retinal microglia/macrophages would
      respond to neuronal death after intravitreal kainate injection. An increased
      expression of the complement receptor type 3 (CR3) and an induction of the major
      histocompatibility complex (MHC) class II and ED-1 antigens were mainly observed
      in the inner retina after kainate injection. Prominent cell death revealed by
      Fluoro Jade B (FJB) staining and ultrastructural examination appeared at the
      inner border of the inner nuclear layer (INL) at 1 day post-injection.
      Interestingly, some immunoreactive cells appeared at the outer segment of
      photoreceptor layer (OSPRL) at different time intervals. Our quantitative
      analysis further showed that CR3 immunoreactivity was drastically increased
      peaking at 7 days but subsided thereafter. MHC class II and ED-1
      immunoreactivities showed a moderate but steady increase peaking at 3 days and
      declined thereafter. Double labeling study further revealed that retinal
      microglia/macrophages expressed concurrently CR3 and ED-1 antigens (OX-42+/ED-1+)
      or MHC class II molecules (OX-42+/OX-6+) and remained branched in shape at early
      stage of kainate challenge. By electron microscopy, microglia/macrophages with
      CR3 immunoreactivity displayed abundant cytoplasm containing a few vesicles and
      phagosomes. Other cells ultrastructurally similar to Muller cells or astrocytes
      could also engulf exogenous substances. In conclusion, retinal
      microglia/macrophages responded vigorously to kainate-induced neuronal cell death
      that may also trigger the recruitment of macrophages from neighboring tissues and
      induce the phagocytotic activity of cells other than retinal
      microglia/macrophages.

PMID- 16458384
TI  - Assemblage of novel release modules for the development of adaptable drug
      delivery systems.
AB  - The aim of this paper was to study the applicability of the release module
      assemblage technology for an adaptable control of drug delivery rate and site.
      The elementary release module was a swellable matrix having one base convex and
      the other concave, named Dome Matrix. The swelling and release behavior of the
      release module was studied. The presence of the convex and concave bases in the
      swellable matrix slightly changed the overall drug delivery kinetics exhibited by
      a flat base cylindrical matrix having the same weight and composition. The
      swelling and drug release of the individual bases of the matrix was also studied
      to investigate the effect of the surface shape. The concave, convex and flat
      bases exhibited different swelling and release kinetics. The convex base released
      drug at faster rate than the concave base, whereas the flat base was
      intermediate. The release mechanisms of convex and concave bases were
      significantly different. The Dome Matrix module was selected for assembling
      several modules in a delivery system obtained by a guided insertion of the convex
      base into the concave base or by concave/concave base sticking. The module
      assemblage shows different drug release behavior depending on the geometry of
      assembled systems.

PMID- 16458385
TI  - Different metabolic correlations of thrombin-activatable fibrinolysis inhibitor
      and plasminogen activator inhibitor-1 in non-obese type 2 diabetic patients.
AB  - We investigated the plasma levels of thrombin-activatable fibrinolysis inhibitor
      (TAFI), plasminogen activator inhibitor-1 (PAI-1) and their relation with
      clinical and metabolic parameters in non-obese type 2 diabetic patients. The
      plasma levels of TAFI and PAI-1 were evaluated in 47 non-obese type 2 diabetic
      patients and 31 normal subjects. The intra-abdominal visceral and subcutaneous
      fat areas were measured by computed tomography (CT). The degree of insulin
      resistance was evaluated by the euglycemic-hyperinsulinemic clamp technique using
      artificial pancreas. The plasma levels of TAFI (169.0+/-108.8% versus 103.7+/
      52.3%; p<0.001, mean+/-S.D.) and PAI-1 (82.7+/-54.5ng/ml versus 52.9+/-51.7ng/ml;
      p<0.05) were significantly higher in non-obese type 2 diabetic patients than in
      normal subjects. Univariate analysis showed that the plasma TAFI levels are
      significantly and inversely correlated with the glucose infusion rate (GIR) (r=
      0.42, p<0.005) in all diabetic patients. Moreover, the plasma levels of TAFI were
      significantly correlated with fasting plasma glucose levels (r=0.47, p<0.001) and
      HbA(1c) (r=0.38, p<0.005) in all subjects. The plasma levels of PAI-1 were
      significantly and proportionally correlated with the visceral fat area (r=0.42,
      p<0.005) and body mass index (r=0.33, p<0.05). There was no significant
      correlation between plasma levels of TAFI and PAI-1 (r=0.04). These results show
      that the plasma levels of TAFI and PAI-1 differently correlate with insulin
      resistance and visceral fat accumulation, suggesting that different factors are
      implicated in the plasma elevation of TAFI and PAI-1 in non-obese type 2 diabetes
      mellitus.

PMID- 16458386
TI  - Toll-like receptor 9 (TLR9) is present in murine liver sinusoidal endothelial
      cells (LSECs) and mediates the effect of CpG-oligonucleotides.
AB  - BACKGROUND/AIMS: Bacterial DNA and synthetic oligonucleotides containing
      unmethylated motifs have become the focus of many studies due to their ability to
      activate cells of the innate immune system through interaction with Toll-like
      receptor 9 (TLR9). This study was undertaken to investigate if and how CpG
      oligonucleotides (CpGs) activate liver sinusoidal endothelial cells (LSECs),
      known to be the main site of clearance of DNA-oligonucleotides from the
      circulation. METHODS: Expression of TLR9 was analyzed by RT-PCR and
      immunohistochemistry. Production of IL-1beta and IL-6 was measured by ELISA.
      RESULTS: Here we show for the first time that mouse LSECs express TLR9 mRNA and
      protein. Moreover, our findings suggest that CpGs are first taken up by LSECs by
      scavenger receptor(s)-mediated endocytosis, and then join TLR9 in the lysosomal
      compartments. Furthermore, we found that uptake of CpGs in LSECs results in the
      activation of transcription factor NF-kappaB and secretion of IL-1beta and IL-6.
      CONCLUSIONS: The presence of functional TLR9 in LSECs emphasizes the importance
      of these cells in the innate defense mechanisms of the liver.

PMID- 16458387
TI  - Effects of liver growth factors on hepadnavirus replication in chronically
      infected duck hepatocytes.
AB  - BACKGROUND/AIMS: Duck hepatitis B virus (DHBV) replication is up-regulated by
      cell cycle during the early infection of primary duck but the effect of cell
      cycle on DHBV replication in chronically infected hepatocyte is not known.
      METHODS: Hepatocytes obtained from DHBV congenitally infected embryos were used.
      Cell proliferation was controlled by addition of liver growth factors and the
      impact on viral replication analyzed. RESULTS: EGF induced cell proliferation is
      associated with a slight increase in CCC DNA synthesis and a decrease in viral
      transcription. Conversely, TGFbeta blocked cell cycle progression, diminished CCC
      DNA synthesis but increased viral transcription. CONCLUSIONS: Cell proliferation
      decreases DHBV transcription but this effect seems to be compensated by an
      opposite effect on the synthesis of CCC DNA resulting in a global moderate effect
      on viral replication. Our results also indicate that after division of
      chronically infected hepatocytes both daughter cells are infected, confirming
      that liver regeneration is not sufficient to induce CCC DNA eradication as
      suggested by the lack of effect of some long term anti-HBV therapies.

PMID- 16458388
TI  - The expression of mesenchymal, neural and haematopoietic stem cell markers in
      adult hepatocytes proliferating in vitro.
AB  - BACKGROUND/AIMS: Cultured adult hepatocytes may be stimulated into clonal
      expansion. We raise the question whether adult hepatocytes proliferating in vitro
      recapitulate the early process of hepatic development. METHODS: A non-enzymatic
      method was used to isolate hepatocytes free of contamination with non-parenchymal
      cells. Hepatocytes were stimulated into proliferation in the presence of mitogens
      and conditioned media from non-parenchymal cell and hepatocyte culture
      supernatants. Immunofluorescence methods and PCR analysis were used to
      demonstrate immunophenotypical characteristics and gene expression profiles
      similar to those of progenitor cells. RESULTS: Rapid growth occurred during the
      first 7 days of culture. Cells continued to express hepatic markers
      (phosphoenolpyruvate carboxykinase, cytokeratin 18, transferrin and
      dipeptidylpeptidase IV), but the gap junction protein connexin 32 was down
      regulated. In the early stage of proliferation, cells started to express biliary
      and extrahepatic progenitor markers (cytokeratin 19, CD49b, CD49f, nestin,
      vimentin, Thy1 and c-kit), followed by cytokeratin 7, connexin 43, and neural
      cell adhesion molecule. Co-expression of the epithelial liver progenitor marker
      alpha-foetoprotein with either nestin (neural marker) or Thy1 (mesenchymal
      marker) was also demonstrated. CONCLUSIONS: Mature hepatocytes reveal their
      potential to regain a spectrum of progenitor markers from different germ layers,
      suggesting enormous plasticity and differentiation potential of adult liver
      cells.

PMID- 16458389
TI  - A software package to improve image quality and isolation of objects of interest
      for quantitative stereology studies of rat hepatocarcinogenesis.
AB  - In the studies of quantitative stereology of rat hepatocarcinogenesis, we have
      used image analysis technology (automatic particle analysis) to obtain data such
      as liver tissue area, size and location of altered hepatic focal lesions (AHF),
      and nuclei counts. These data are then used for three-dimensional estimation of
      AHF occurrence and nuclear labeling index analysis. These are important
      parameters for quantitative studies of carcinogenesis, for screening and
      classifying carcinogens, and for risk estimation. To take such measurements,
      structures or cells of interest should be separated from the other components
      based on the difference of color and density. Common background problems seen on
      the captured sample image such as uneven light illumination or color shading can
      cause severe problems in the measurement. Two application programs (BK_Correction
      and Pixel_Separator) have been developed to solve these problems. With
      BK_Correction, common background problems such as incorrect color temperature
      setting, color shading, and uneven light illumination background, can be
      corrected. With Pixel_Separator different types of objects can be separated from
      each other in relation to their color, such as seen with different colors in
      immunohistochemically stained slides. The resultant images of such objects
      separated from other components are then ready for particle analysis. Objects
      that have the same darkness but different colors can be accurately differentiated
      in a grayscale image analysis system after application of these programs.

PMID- 16458390
TI  - Impact of the gliotoxin L-serine-O-sulphate on cellular metabolism in cultured
      rat astrocytes.
AB  - L-serine-O-sulphate is a member of a group of amino acids collectively called
      gliotoxins and is a substrate for the high affinity sodium-dependent glutamate
      transporters. Previous studies have shown that it is toxic to primary cultures of
      astrocytes but the mode of toxicity is unknown. The current study demonstrates
      that L-serine-O-sulphate, at a sub-toxic concentration (400 microM), causes
      significant disruption to glucose and alanine metabolism in cultures of rat
      cortical astrocytes. More specifically, using (13)C NMR spectroscopy a
      significant reduction in labelled end products from [1-(13)C]glucose and [3
      (13)C]alanine was found in the presence of L-serine-O-sulphate. Additionally,
      using [2-(13)C]glycine a 27% reduction in de novo glutathione synthesis was
      observed in the presence of the gliotoxin. Incubation of the cells with L-serine
      O-sulphate reduced the activity of alanine and aspartate aminotransferase by 53%
      and 67%, respectively. Collectively these results show that the gliotoxin, L
      serine-O-sulphate, causes major disruptions to metabolic pathways in primary
      cultures of astrocytes.

PMID- 16458391
TI  - Expression of mDab1 promotes the stability and processing of amyloid precursor
      protein and this effect is counteracted by X11alpha.
AB  - The cytoplasmic tail of amyloid precursor protein (APP) possesses the NPTY motif
      to which several phosphotyrosine-binding domain-containing proteins bind,
      including X11alpha and mDab1. X11alpha has been shown to slow cellular APP
      processing and reduce secretion of Abeta peptides. However, the effect of mDab1
      on APP processing has not been determined. Here, we show that mDab1 increases the
      levels of cellular mature APP and promotes its processing by the secretases in
      both transiently transfected HEK 293 cells and in neuroglioma U251 cells. These
      effects derive specifically from the interaction of APP with mDab1 since they are
      not observed in APP deletion mutants lacking the interaction module NPTY. We
      further demonstrate that mDab1 enhances cell surface expression of APP, possibly
      by interfering with its endocytosis. Interestingly, X11alpha and mDab1 exert
      opposing effects on APP processing. However, when both proteins are co-expressed
      the effect of X11alpha overrides that of mDab1. Taken together, these results
      suggest that the relative stoichiometry and binding affinity of the adaptor
      proteins determines the final outcome on APP metabolism.

PMID- 16458392
TI  - QSAR studies on benzopyran potassium channel activators.
AB  - QSAR studies on a series of benzopyrans as potassium channel activators have been
      carried out using a large set of distance-based topological indices. In addition,
      the molecular descriptors namely: negentropy and molecular redundancy indices
      have also been used. The relaxant potency in rat trachea, expressed as pEC(50)
      was used for biological characterization of the benzopyrans. The results have
      shown that pEC(50) can be modeled excellently in multiparametric model in that we
      have to include an indicator parameter. The predictive powers of the proposed
      models are discussed on the bases of cross-validation parameters.

PMID- 16458393
TI  - Polar, functionalized guanine-O6 derivatives resistant to repair by O6
      alkylguanine-DNA alkyltransferase: implications for the design of DNA-modifying
      drugs.
AB  - The protein O6-alkylguanine-DNA alkyltransferase (Atase) is responsible for the
      repair of DNA lesions generated by several clinically important anti-cancer
      drugs; this is manifest as active resistance in those cancer cell lines
      proficient in Atase expression. Novel O6-substituted guanine analogues have been
      synthesized, bearing acidic, basic and hydrogen bonding functional groups. In
      contrast to existing O6-modified purine analogues, such as methyl or benzyl, the
      new compounds were found to resist repair by Atase even when tested at
      concentrations much higher than O6-benzylguanine, a well-established Atase
      substrate active both in vitro and in vivo. The inactivity of the new purines as
      covalent substrates for Atase indicates that agents to deliver these groups to
      DNA would represent a new class of DNA-modifying drug that circumvents Atase
      mediated resistance.

PMID- 16458394
TI  - Microvascular stress analysis. Part I: simulation of microvascular anastomoses
      using finite element analysis.
AB  - PURPOSE OF THE STUDY: To develop a finite element model (FEM) to study the effect
      of the stress and strain, in microvascular anastomoses that result from the
      geometrical mismatch of anastomosed vessels. MATERIAL AND METHODS: FEMs of end-to
      end and end-to-side anastomoses were constructed. Simulations were made using
      finite element software (NISA). We investigated the angle of inset in the end-to
      side anastomosis and the discrepancy in the size of the opening in the vessel
      between the host and recipient vessels. The FEMs were used to predict principal
      and shear stress and strain at the position of each node. RESULTS: Two types of
      vascular deformation were predicted during different simulations: longitudinal
      distortion, and rotational distortion. Stress values ranged from 151.1 to
      282.4MPa for the maximum principal stress, from -122.9 to -432.2MPa for the
      minimum principal stress, and from 122.1 to 333.1MPa for the maximum shear
      stress. The highest values were recorded when there was a 50% mismatch in the
      diameter of the vessels at the site of the end-to-end anastomosis. CONCLUSION:
      The effect of the vessel's size discrepancy on the blood flow and deformation was
      remarkable in the end-to-end anastomosis. End-to-side anastomosis was superior to
      end-to-end anastomosis. FEM is a powerful tool to study vascular deformation, as
      it predicts deformation and biomechanical processes at sites where physical
      measurements are likely to remain impossible in living humans.

PMID- 16458395
TI  - Antibiotics for patients with zygomatic fractures into the maxillary antrum.

PMID- 16458396
TI  - Local application of ice bags did not affect postoperative facial swelling after
      oral surgery in rabbits.
AB  - We wanted to find out what effect the local application of ice bags had on facial
      swelling after oral operations in rabbits. We anaesthetised 26 French rabbits and
      did identical oral operations simultaneously on the right and left sides of the
      maxilla. Postoperatively, we applied ice bags to either the right or left side of
      the face (randomly selected) for 20-min periods for 4h. The transverse dimensions
      of the right and left sides of the face were measured preoperatively, and 24h,
      48h, and 7 days postoperatively. All animals had measurable right and left
      postoperative facial swelling, but there was no significant difference between
      the test and control sides 24 or 48h postoperatively and no measurable swelling
      in any of the animals after 7 days.

PMID- 16458397
TI  - Effects of simultaneous ozone exposure and nitrogen loads on carbohydrate
      concentrations, biomass, growth, and nutrient concentrations of young beech trees
      (Fagus sylvatica).
AB  - Beech seedlings were grown under different nitrogen fertilisation regimes (0, 20,
      40, and 80 kg Nha(-1)yr(-1)) for three years and were fumigated with either
      charcoal-filtered (F) or ambient air (O3). Nitrogen fertilisation increased leaf
      necroses, aphid infestations, and nutrient ratios in the leaves (N:P and N:K), as
      a result of decreased phosphorus and potassium concentrations. For plant growth,
      biomass accumulation, and starch concentrations, a positive nitrogen effect was
      found, but only for fertilisations of up to 40 kg Nha(-1) yr(-1). The highest
      nitrogen load, however, reduced leaf area, leaf water content, growth, biomass
      accumulation, and starch concentrations, whereas soluble carbohydrate
      concentrations were enhanced. The ozone fumigation resulted in reduced leaf area,
      leaf water content, shoot growth, root biomass accumulation, and decreased
      starch, phosphorus, and potassium concentrations, increasing the N:P and N:K
      ratios. A combined effect of the two pollutants was detected for the leaf area
      and the shoot elongation, where ozone fumigation amplified the nitrogen effects.

PMID- 16458398
TI  - Incidence of ozone symptoms on vegetation within a National Wildlife Refuge in
      New Jersey, USA.
AB  - During 1993-1996 and 2001-2003, we evaluated the percentage of plants (incidence)
      exhibiting ozone-induced foliar symptoms on vegetation within a National Wildlife
      Refuge located along the Atlantic Ocean coast of New Jersey, USA. Incidence
      varied among plant species and years. Bioindicator plants most sensitive to
      ozone, across all years, included native common milkweed (Asclepias syriaca) and
      wild grape (Vitis spp.), as well as introduced tree-of-heaven (Ailanthus
      altissima). Less sensitive bioindicators included Virginia creeper
      (Parthenocissus quinquefolia) and winged sumac (Rhus coppolina). Black cherry
      (Prunus serotina) and sassafras (Sassafras albidum) were least sensitive. The
      greatest incidence of ozone symptoms, across all plant species, occurred in 1996,
      followed by 2001>1995>1994>1993>2003>2002. A model was developed that showed a
      statistically significant relationship between incidence of ozone symptoms and
      the following parameters: plant species, Palmer Drought Severity Index, and the
      interaction of W126 x N100 measures of ambient ozone.

PMID- 16458399
TI  - Abiotic ecotypes in south-central Spanish rivers: reference conditions and
      pollution.
AB  - Physico-chemical water quality in five of Spain's main rivers was assessed during
      the years 2001-2003. A previous physiographical river typology was carried out by
      applying System B of the Water Framework Directive (2000/60/CE) which
      distinguished four main river ecotypes: calcareous headwaters, siliceous rivers,
      plain rivers, and large rivers. The physiographical classification into river
      ecotypes also corresponded to distinct hydrochemical types. Reference values of
      ammonium, nitrate and phosphate fitted for local river ecotypes surpassed only
      slightly the natural and background levels established by the European
      Environmental Agency (EEA, 2003). Half of the sampled sites were above the limits
      established as reference conditions. Additionally, concentrations of ammonium,
      nitrite, nitrate, and phosphate increased when more percentage of land was
      dedicated to agriculture and less to forest land.

PMID- 16458400
TI  - Distribution and relationships between selected chemical elements in green alga
      Enteromorpha sp. from the southern Baltic.
AB  - The concentrations of heavy metals (Cd, Cu, Ni, Pb, Zn and Mn) and macroelements
      (K, Na, Ca and Mg) were determined in green alga Enteromorpha sp. from the
      coastal zone of the southern Baltic including Gulf of Gdansk and Vistula Lagoon
      in 2000-2003. In order to estimate the degree of accumulation of each element by
      the green alga, concentration and discrimination factors (CFs) with respect to
      seawater were calculated. The results of factor analysis (FA) and ANOVA clearly
      indicate geographical differences between concentrations of chemical elements.
      Enteromorpha sp. from Vistula Lagoon and the southern Baltic exhibited higher
      levels of Mn and Ni, and Na and K, respectively. Anthropogenic impact of Cu, Pb
      and Zn, possibly originated from municipal sewage, was identified in alga samples
      collected in the Gulf of Gdansk, especially in the vicinity of Gdynia. From
      comparison our data with those published earlier results that Pb content in
      Enteromorpha sp. from the Gulf of Gdansk decreased within 1978-2003 reflecting
      reducing use of leaded petrol in Baltic countries in this period. The alga
      Enteromorpha sp. can be used for biomonitoring surveys of metal contaminants in
      coastal areas of the Baltic Sea.

PMID- 16458402
TI  - An islet of social ability in Asperger Syndrome: judging social attributes from
      faces.
AB  - We asked adults with Asperger Syndrome to judge pictorial stimuli in terms of
      certain social stereotypes to evaluate to what extent they have access to this
      type of social knowledge. Sixteen adults with Asperger Syndrome and 24 controls,
      matched for age and intelligence, were presented with sets of faces, bodies and
      objects, which had to be rated on a 7-point scale in terms of trustworthiness,
      attractiveness, social status, and age, or, in the case of objects, price.
      Despite impaired performance on two important aspects of social cognition (second
      order mentalizing and face recognition) the social judgements of the individuals
      with Asperger Syndrome were just as competent and consistent as those of their
      matched controls, with only one exception: there was a trend for them to be less
      able to judge the attractiveness of faces if they were the same sex. We explain
      this difference in terms of a weakness in mentalizing, specifically the ability
      to take a different point of view: While all other stereotypic attributions could
      be made from an egocentric point of view, judging the attractiveness of faces of
      one's own sex requires taking the perspective of someone of the opposite sex, a
      challenge for people with mentalizing problems. We conclude that individuals with
      Asperger Syndrome show preserved aspects of social knowledge, as revealed in the
      attribution of stereotypes to pictures of people. These findings suggest that
      there are dissociable subcomponents to social cognition and that not all of these
      are compromised in Asperger Syndrome.

PMID- 16458401
TI  - Response monitoring, the error-related negativity, and differences in social
      behavior in autism.
AB  - Children with autism not only display social impairments but also significant
      individual differences in social development. Understanding the source of these
      differences, as well as the nature of social impairments, is important for
      improved diagnosis and treatments for these children. Current theory and research
      suggests that individual differences in response monitoring, a specific function
      of the anterior cingulate cortex (ACC), may contribute to social-emotional and
      social-cognitive impairments and individual differences in autism. To examine
      this hypothesis, we used a modified flanker task to assess an ERP index of
      response monitoring, the error-related negativity (ERN), in a sample of higher
      function children with autism (HFA) and an IQ-matched control sample. The results
      revealed a significant Diagnostic group by Verbal IQ interaction on ERN amplitude
      indicating that the most verbally capable HFA children displayed significantly
      larger ERN amplitudes than did the control children. Within the HFA sample,
      greater ERN amplitude was also related to parent reports of fewer symptoms of
      social interaction impairments, fewer internalizing problems, but more
      externalizing problems, although these associations were reduced to
      nonsignificance when medication status was controlled. The latter results
      complement previous observations from imaging studies of a significant
      association between ACC activity and social symptoms and impairments in autism.
      The implications of these results for future research on brain-behavior
      relations, as well as treatment related research with children with autism are
      discussed.

PMID- 16458403
TI  - Theoretical insights into the mechanism of action of atypical antipsychotics.
AB  - The present work discusses some theoretical mathematical results that can be
      derived from the theory of receptor binding linked with PET experimental data and
      presents insights to the understanding of the differences between typical and
      atypical profile of antipsychotics regarding the generation of extrapyramidal
      syndrome. The first part of the paper discusses the importance of the drug
      affinity to dopamine D2 receptors (D2R) and of the therapeutic window of drug
      concentration for antipsychotic action without EPS, whereas the second part
      discusses the contribution of the plasma half-life in the time-course of D2R
      occupancy. Together with current experimental data, we concluded that the key
      factors leading to an atypical profile would be adequate posology, low affinity
      of the drug to D2R and/or short plasma half-life.

PMID- 16458404
TI  - Drugs on the web; the Psychonaut 2002 EU project.
AB  - PURPOSE: Only a few formal assessments of websites with drug-related contents
      have been carried out. We aimed here at fostering collection and analysis of data
      from web pages related to information on consumption, manufacture and sales of
      psychoactive substances. GENERAL METHODS: An 8-language, two-engine, assessment
      of the information available in a purposeful sample of 1633 unique websites was
      carried out. FINDINGS: A pro-drug and a harm reduction approach were evident,
      respectively, in 18% and 10% of websites accessed. About 1 in 10 websites offered
      either psychoactive compounds for sale or detailed data on drugs'
      synthesis/extraction procedures. Information on a number of psychoactive
      substances and on unusual drugs' combinations not found in the Medline was
      elicited. CONCLUSIONS: This represents the first review which is both
      comprehensive and multilingual of the online available information on
      psychoactive compounds. Health professionals may need to be aware of the web
      being a new drug resource for information and possibly purchase.

PMID- 16458405
TI  - Does work on obsessive-compulsive spectrum disorders contribute to understanding
      the heterogeneity of obsessive-compulsive disorder?
AB  - BACKGROUND: There is a growing literature on the concept of an obsessive
      compulsive spectrum of disorders. Here, we consider the different dimensions on
      which obsessive-compulsive spectrum (OCSDs) lie, and focus on how the concepts
      from this literature may help understand the heterogeneity of obsessive
      compulsive disorder (OCD). METHODS: A computerized literature search (MEDLINE:
      1964-2005) was used to collect studies addressing different dimensions on which
      the OCSDs lie. Against this backdrop, we report on a cluster analysis of OCSDs
      within OCD. RESULTS: OCSDs may lie on several different dimensions. Our cluster
      analysis found that in OCD there were 3 clusters of OCD spectrum symptoms: (1)
      "Reward deficiency" (including trichotillomania, pathological gambling,
      hypersexual disorder and Tourette's disorder), (2) "Impulsivity" (including
      compulsive shopping, kleptomania, eating disorders, self-injury and intermittent
      explosive disorder), and (3) "Somatic" (including body dysmorphic disorder and
      hypochondriasis). CONCLUSIONS: It is unlikely that OC symptoms and disorders fall
      on any single phenomenological dimension; instead, multiple different constructs
      may be required to map this nosological space. Although there is evidence for the
      validity of some of the relevant dimensions, additional work is required to
      delineate more fully the endophenotypes that underlie OC symptoms and disorders.

PMID- 16458406
TI  - Probabilistic dietary exposure assessment taking into account variability in both
      amount and frequency of consumption.
AB  - Probabilistic dietary exposure assessments that are fully based on Monte Carlo
      sampling from the raw intake data may not be appropriate. This paper shows that
      the data should first be analysed by using a statistical model that is able to
      take the various dimensions of food consumption patterns into account. A
      (parametric) model is discussed that takes into account the interindividual
      variation in (daily) consumption frequencies, as well as in amounts consumed.
      Further, the model can be used to include covariates, such as age, sex, or other
      individual attributes. Some illustrative examples show how this model may be used
      to estimate the probability of exceeding an (acute or chronic) exposure limit.
      These results are compared with the results based on directly counting the
      fraction of observed intakes exceeding the limit value. This comparison shows
      that the latter method is not adequate, in particular for the acute exposure
      situation. A two-step approach for probabilistic (acute) exposure assessment is
      proposed: first analyse the consumption data by a (parametric) statistical model
      as discussed in this paper, and then use Monte Carlo techniques for combining the
      variation in concentrations with the variation in consumption (by sampling from
      the statistical model). This approach results in an estimate of the fraction of
      the population as a function of the fraction of days at which the exposure limit
      is exceeded by the individual.

PMID- 16458407
TI  - In-hospital cardiac arrest--an Utstein style report of seven years experience
      from the Sahlgrenska University Hospital.
AB  - BACKGROUND: In-hospital cardiac arrest is one of the most stressful situations in
      modern medicine. Since 1997, there has been a uniform way of reporting - the
      Utstein guidelines for in-hospital cardiac arrest reporting. MATERIAL AND
      METHODS: We have studied all consecutive cardiac arrest in the Sahlgrenska
      University Hospital (SU) between 1994 and 2001 for who the rescue team was
      alerted in all 833 patients. The primary endpoint for this study was survival to
      discharge. RESULTS: Thirty-seven percent survived to hospital discharge. Among
      patients who were discharged alive, 86% were alive 1 year later. The survivors
      have a good cerebral outcome (94% among those who were discharged alive had
      cerebral performance category (CPC) score 1 or 2). The organization at SU is
      efficient; 80% of the cardiac arrest had CPR within 1 min. Time from cardiac
      arrest to first defibrillation is a median of 2 min. Almost two-thirds of the
      patients were admitted for cardiac related diagnoses. CONCLUSION: The current
      study is the largest single-centre study of in hospital cardiac arrest reported
      according to the Utstein guidelines. We report a high survival for in-hospital
      cardiac arrest. We have pointed out that a functional chain of survival, short
      intervals before the start of CPR and defibrillation are probably contributing
      factors for this.

PMID- 16458408
TI  - Effects of levosimendan in normodynamic endotoxaemia: a controlled experimental
      study.
AB  - OBJECTIVES: Levosimendan is an inotropic and vasodilator drug that has proved to
      be useful in cardiogenic shock. Pretreatment with levosimendan in experimental
      hypodynamic septic shock in pigs has shown valuable effects in oxygen transport.
      Our goal was to assess the effects of levosimendan in a normodynamic model of
      endotoxaemia. METHODS: Twelve sheep were anaesthetized and mechanically
      ventilated. After taking basal haemodynamic and oxygen transport measurements,
      sheep were assigned to two groups during 120 min: (1) endotoxin (5 microg/kg
      endotoxin); (2) levosimendan (5 microg/kg endotoxin plus levosimendan 200
      microg/kg followed by 200 microg/kg/h). Both groups received hydration of 20
      ml/kg/h of saline solution. RESULTS: In the endotoxin group, cardiac output,
      intestinal blood flow and systemic and intestinal oxygen transports and
      consumptions (DO(2) and VO(2)) remained unchanged. In the levosimendan group,
      systemic and intestinal DO(2) were significantly higher than in the endotoxin
      group. Because stroke volume did not change (basal versus 120': 0.9+/-0.1 ml/kg
      versus 0.9+/-0.2 ml/kg, p=0.3749), the elevation in cardiac output by
      levosimendan (145+/-17 ml/min/kg versus 198+/-16 ml/min/kg, p=0.0096) was related
      to an increased heart rate (159+/-32 beats l/min versus 216+/-19 beats l/min,
      p=0.0037). Levosimendan precluded the development of gut intramucosal acidosis at
      120' (endotoxin versus levosimendan, ileal intramucosal-arterial PCO(2)
      difference: 19+/-4 Torr versus 10+/-4 Torr, p=0.0025). However, levosimendan
      decreased mean arterial blood pressure (99+/-20 Torr versus 63+/-13 Torr,
      p=0.0235) and increased blood lactate levels (2.4+/-0.9 mmol/l versus 4.8+/-1.5
      mmol/l, p=0.0479). All p-values are differences in specific points (paired or
      unpaired t-test with Bonferroni correction) after two-way repeated measures
      ANOVA. A p-value<0.05 was considered significant. CONCLUSIONS: Levosimendan
      improved oxygen transport and prevented the development of intramucosal acidosis
      in this experimental model of endotoxaemia. However, systemic hypotension and
      lactic acidosis occurred. Additional studies are needed to show if different
      doses and timing of levosimendan administration in septic shock might improve gut
      perfusion without adverse effects.

PMID- 16458409
TI  - New use of a tracheal tube for rescue breathing in laryngectomees in the
      community.
AB  - The currently recommended method for rescue breathing in people who have had a
      laryngectomy is mouth-to-stoma. Even if they know what to do, by-standers are
      likely to find this technique unhygienic and therefore unacceptable. There is no
      equivalent of the pocket face mask for laryngectomees. This paper describes the
      practical differences that affect rescue breathing in patients with laryngectomy
      stomas and proposes a new use of a tracheal tube for rescue breathing in
      laryngectomees. Ten patients with permanent tracheal stomas scheduled for ENT
      surgery were ventilated successfully through a tracheal tube with the cuff
      applied to the outside of their tracheal stomas, following induction of
      anaesthesia and before the start of surgery. Observations of oxygen saturation,
      end-tidal carbon dioxide, expired tidal volume and chest movements were within
      acceptable limits. This device was simple to use and is hygienic and inexpensive.
      Laryngectomees' relatives, friends or carers with minimal training could use the
      tube in a mouth-to-tube-to-stoma technique should the need for rescue breathing
      arise. It could also be used by paramedic and medical staff in a mouth or bag-to
      tube-to-stoma technique until a definitive airway can be inserted.

PMID- 16458411
TI  - Radiological and electrocardiographic changes following thrombolysis for acute
      pulmonary embolism with haemodynamic compromise.

PMID- 16458410
TI  - The knowledge and perceptions of medical personnel relating to outcome after
      cardiac arrest.
AB  - OBJECTIVE: We sought to evaluate the knowledge of probable outcome by medical
      personnel for in-hospital and out-of-hospital cardiac arrests, and self-reported
      history of CPR training referrals for family members of cardiac patients.
      METHODS: One hundred people from each of three population lists were randomly
      selected at a large, urban school of medicine and affiliated medical center: (1)
      year III and IV medical students; (2) residents in family medicine, emergency
      medicine, internal medicine, anesthesia, and surgery; (3) attending physicians in
      the same departments. A questionnaire was distributed that elicited estimates of
      in-hospital and out-of-hospital cardiac arrest (IHCA and OHCA, respectively)
      survival rates, and CPR training referral history. Estimates were compared
      against published data for accuracy (IHCA: 5-20%; OHCA 1-10%) RESULTS: The
      overall response rate was 63%. Accurate in-hospital cardiac arrest estimates [%
      (95% CI)] of survival were provided by 51.1% (36.8-63.4%), 47.3% (35.9-58.7%),
      and 36.7% (23.2-50.2%) of students, residents, and attending physicians,
      respectively. Accurate out-of-hospital estimates of survival were provided by
      51.1% (36.8-63.4%), 52.1% (40.6-63.5%), and 70.8% (57.9-83.7%), respectively.
      Most thought that family members of cardiac patients ought to be CPR trained
      (92.6%). However, few had referred any for training in the past year (16.5%).
      There was strong support across respondent groups for including death
      notification information in the ACLS training program, with 80.4% of all
      respondents in favor. CONCLUSIONS: This study demonstrates that medical
      experience is not associated with accurate estimates of cardiac arrest survival.
      Overwhelmingly, medical personnel believe family members should be trained to
      perform CPR, however, few refer family members for CPR training.

PMID- 16458412
TI  - Confusion between monophasic and biphasic defibrillators.

PMID- 16458413
TI  - Magnetic resonance images in hanging.
AB  - Hanging is a devastating method of suicide and unfortunately is common in Japan.
      Although several CT findings of the head have been reported, there have not been
      any reports about magnetic resonance imaging (MRI) in hanging. We report here
      interesting MRI findings in a patient after hanging. A 39-year-old woman was
      transferred to our department after attempting suicide by hanging. Respiration
      had probably ceased for about three minutes but heart had not stopped when she
      was pulled down by her father. After her father performed cardiopulmonary
      resuscitation, she started to breathe immediately. She was treated conservatively
      in our intensive care unit for 14 days, her condition became stable. Ten days
      after admission, MRI demonstrated symmetrical hyperintensity on T1-weighted
      images and relative hyperintensity on T2 weighted images in bilateral lentiform
      nuclei and medial thalami. There have been several reports about characteristic
      MRI findings in the case of acute global cerebral ischaemia caused by severe
      hypoglycaemia or longstanding cardiopulmonary arrest. It was postulated that
      these specific findings reflected tissue degeneration, deposition of mineral
      substances, or lipid accumulation. These MRI findings suggest that severe acute
      global cerebral hypoperfusion also occurs in hanging in the same way as in long
      standing cardiopulmonary arrest and that hanging has devastating sequelae.

PMID- 16458414
TI  - Complete neurological recovery following delayed initiation of hypothermia in a
      victim of warm water near-drowning.
AB  - Induced hypothermia has been demonstrated to improve outcome following cardiac
      arrest and is now widely endorsed. However, the optimal method of cooling and the
      identification of patients most likely to benefit from this therapy remains to be
      determined. We report a patient in whom there was a long delay in return of
      spontaneous circulation (at least 45 min) and the initiation of induced
      hypothermia (12 h) who made an almost complete neurological recovery following
      cardiac arrest from warm-water near-drowning.

PMID- 16458415
TI  - Amine terminated G-6 PAMAM dendrimer and its interaction with DNA probed by
      Hoechst 33258.
AB  - Fluorescence characteristics of Hoechst 33258 bound to G-6 dendrimer, to the DNA
      G-6 dendrimer complex, and to DNA were compared with that in an aqueous solution.
      The spectral properties including fluorescence emission spectrum, accessibility
      of anionic quencher, as well as the fluorescence decay time of the Hoechst 33258
      are different for all three conditions, indicating that the environments in these
      conditions are different. Close analysis of the fluorescence properties led us to
      suggest that Hoechst 33258 located at or near the contact area of the dendrimer
      and DNA in the DNA-G-6 complex. In the complex, in the absence of Hoechst 33258,
      the shape of the circular dichroism in the DNA absorption region remained,
      indicating that DNA is in B form in the complex. On the other hand, the magnitude
      of linear dichroism (LD) decreased upon DNA-G-6 dendrimer complex formation. The
      decrease in LD magnitude reflects the shortening of the DNA contour length, which
      is expected from the fact that a large part of linear DNA is required to wrap the
      surface of G-6 dendrimer.

PMID- 16458416
TI  - Early start to therapy preserves kidney function in spina bifida patients.
AB  - OBJECTIVE: Renal scarring and renal failure remain life-threatening for children
      born with spinal dysraphism. We reviewed our data of spina bifida patients to
      evaluate whether optimal treatment of the neurogenic bladder from birth onwards
      can preserve kidney function. METHODS: We reviewed data on all newborns with
      spinal dysraphism who were referred to our hospital between January 1988 and June
      2001. We looked at their situations at referral and at follow-up: the type of
      treatment, antimuscarinic agents, clean intermittent catheterisation (CIC),
      antibiotic prophylaxis, and operations (sling procedures, bladder augmentations,
      antireflux procedures). Renal function (ultrasound, DMSA scan, serum creatinin,
      creatinin clearance) and bladder function (urodynamic studies) were evaluated
      over time. RESULTS: Data of 144 children of 176 could be evaluated by the end of
      the study: 5 patients had pre-existing renal abnormalities, 69 had an overactive
      sphincter, 27 had reflux, and six had renal scarring. None are currently
      developing end-stage renal disease. All patients with spina bifida aperta started
      CIC and antimuscarinic therapy shortly after birth. Five of the six patients with
      renal scarring were started on therapy with intermittent catheterisation and
      antimuscarinic therapy several months after birth. Sixty-three of 82 children
      with spina bifida were dry at school age (age six), although 37 of these had not
      had an operation. CONCLUSION: We show that an early start to therapy helps to
      safeguard renal function for children born with spina bifida. Our data support
      other recent reports that children born with spina bifida can probably use their
      own kidneys for a lifetime, if they are given adequate urological treatment. To
      protect the upper urinary tract, we need to ensure low intravesical pressure by
      starting children early on CIC (the preferred treatment); antimuscarinic agents
      to counteract detrusor instability are indispensable in most cases. Proactive
      treatment of risks for upper tract deterioration results in a negligible loss of
      renal function, even when early urinary continence is included in the treatment
      protocol.

PMID- 16458417
TI  - Role of quality of life in men with metastatic hormone-refractory prostate
      cancer: how does atrasentan influence quality of life?
AB  - OBJECTIVE: Progression of hormone-refractory prostate cancer (HRPC) is associated
      with skeletal complications and bone pain, which contribute to deterioration in
      quality of life (QOL). The effects of new HRPC therapies on patients' QOL need to
      be studied. Patient-based assessments that help quantify the risk-benefit profile
      of HRPC therapies are warranted. This review summarizes the known QOL literature
      and estimates the potential effect of atrasentan, a novel, selective endothelin A
      receptor antagonist (SERA), on the QOL of HRPC patients. METHODS: Published
      studies were identified through a structured, detailed literature review.
      Clinical studies that report QOL data were reviewed, along with recent QOL data
      from atrasentan studies. RESULTS: HRPC studies have begun to use QOL assessments
      as primary endpoints, but different assessments and therapies are not comparable.
      Very few data integrate QOL with clinical endpoints. Atrasentan clinical trials
      demonstrated a statistically significant difference in the prostate cancer
      specific QOL in favor of atrasentan (p=.032) and an increased quality-adjusted
      time to progression in men with HRPC. CONCLUSIONS: Atrasentan provides QOL
      benefits relevant to HRPC. The quality-adjusted analyses applied in the
      atrasentan studies have begun to lay the foundation for interpreting clinical
      endpoints in conjunction with QOL. These analyses will facilitate better QOL
      comparisons within studies and across trials. Further evaluation of atrasentan in
      HRPC is warranted.

PMID- 16458418
TI  - Adherence to the right diagnostic tools for best outcomes in urethral
      reconstructive surgery.

PMID- 16458419
TI  - Nitro-thiocyanobenzoic acid (NTCB) reactivity of cysteines beta100 and beta110 in
      porcine luteinizing hormone: metastability and hypothetical isomerization of the
      two disulfide bridges of its beta-subunit seatbelt.
AB  - Luteinizing hormone (LH) like all other glycoprotein hormones is composed of two
      dissimilar subunits, alpha and beta, that are non-covalently associated. The
      heterodimer is stabilized by a region of the beta-subunit called the "seatbelt"
      because it wraps around the alpha-subunit and it is fastened by a disulfide
      bridge between cysteines beta26 and beta110. Although all 22 cysteines of porcine
      LH (pLH) are engaged in disulfide bridges, we previously showed that the free
      cysteine-specific reagent NTCB could react with pLH: it slowly cyanylated two
      cysteines in pLH and there was a close relationship between NTCB reaction with
      pLH and association/dissociation kinetics of its subunits. Therefore, cysteines
      beta26 and beta110 were considered as the best candidates for NTCB reaction. In
      order to identify the NTCB-reactive cysteines in pLH we have performed a mass
      spectroscopic analysis of the peptides released after mild basic hydrolysis of S
      cyanylated pLH and its subunits. Only cysteines beta100 and beta110 were found to
      react with NTCB. Since these residues are not linked by a disulfide bridge in the
      crystallographic 3D structure of gonadotropins, it is proposed that their
      respective counterparts (Cysbeta93 and beta26) do not react with NTCB either
      because they are shielded from solvent or because they form a transient bridge.
      In the first hypothesis, both seatbelt bridges would be independently metastable;
      in the second one, a fast reversible isomerization between bridges beta26-beta110
      and beta93-beta100 would occur. Such a reaction could be catalyzed by the
      previously recognized intrinsic protein disulfide isomerase (PDI) activity of
      gonadotropins.

PMID- 16458420
TI  - Epididymal genomics and the search for a male contraceptive.
AB  - This report represents the joint efforts of three laboratories, one with a
      primary interest in understanding regulatory processes in the epididymal
      epithelium (TTT) and two with a primary interest in identifying and
      characterizing new contraceptive targets (DSJ and SAJ). We have developed a
      highly refined mouse epididymal transcriptome and have used it as a starting
      point for determining genes in the human epididymis, which may serve as targets
      for male contraceptives. Our database represents gene expression information for
      approximately 39,000 transcripts, of which over 17,000 are significantly
      expressed in at least one segment of the mouse epididymis. Over 2000 of these
      transcripts are up- or down-regulated by at least four-fold between at least two
      segments. In addition, human databases have been queried to determine expression
      of orthologs in the human epididymis and the specificity of their expression in
      the epididymis. Genes highly regulated in the human epididymis and showing high
      tissue specificity are potential targets for male contraceptives.

PMID- 16458421
TI  - Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced
      angiogenesis.
AB  - A central feature of all solid tumor growth is the presence of
      neovascularization. The CXC chemokines GRO-gamma/CXCL3, ENA-78/CXCL5, and IL
      8/CXCL8 have profound angiogenic potential mediated through the CXCR2 receptor.
      The aim of the present study was to evaluate the expression of the angiogenic
      chemokines in three human pancreatic cancer cell lines and to determine the role
      of these proteins in pancreatic cancer angiogenesis. Secreted CXC protein levels
      in the supernatant of the cell lines were analyzed by ELISA. A rat corneal
      micropocket model was used to determine the angiogenic potential of these
      secreted CXC chemokines in vivo. ELISA confirmed expression of all three tested
      CXC chemokines in the supernatant of two cell lines. In the corneal micropocket
      assay, neovascularization was induced using pelleted supernatant of all three
      cell lines. Using an anti-CXCR2 antibody, neovascularization was significantly
      inhibited in the high expressing BxPC-3 cell line samples. In addition, the
      expression of ENA-78/CXCL5 and IL-8/CXCL8 has been evaluated in human pancreatic
      cancer tissue samples by using immunohistochemistry in order to further
      investigate the potential role of CXC chemokines in pancreatic cancer
      angiogenesis and tumorigenesis.

PMID- 16458422
TI  - Aflatoxin B1-induced DNA damage and its repair.
AB  - Aflatoxin B(1) (AFB(1))-N(7)-guanine is the predominant adduct formed upon the
      reaction of AFB(1)-8,9-exo-epoxide with guanine residues in DNA. AFB(1)-N(7)
      guanine can convert to the ring-opened formamidopyrimidine, or the adducted
      strand can undergo depurination. AFB(1)-N(7)-guanine and AFB(1)
      formamidopyrimidine are thought to be predominantly repaired by nucleotide
      excision repair in bacteria, yeast and mammals. Although AFB(1)
      formamidopyrimidine is removed less efficiently than AFB(1)-N(7)-guanine in
      mammals, both lesions are repaired with equal efficiencies in bacteria,
      reflecting differences in damage recognition between bacterial and mammalian
      repair systems. Furthermore, DNA repair activity and modulation of repair by
      AFB(1) seem to be major determinants of susceptibility to AFB(1)-induced
      carcinogenesis.

PMID- 16458423
TI  - Protective effect of bioantioxidants on argemone oil/sanguinarine alkaloid
      induced genotoxicity in mice.
AB  - Our prior studies have shown that argemone oil (AO) and its alkaloid sanguinarine
      causes DNA damage in mice and Epidemic Dropsy patients. Since some of the
      bioantioxidants including riboflavin and alpha-tocopherol offered protection to
      Epidemic Dropsy patients, a combination of riboflavin and alpha-tocopherol was
      evaluated on AO and sanguinarine induced genotoxicity using alkaline comet assay.
      Single administration of combination of riboflavin (50mg/kg) and alpha-tocopherol
      (150mg/kg) to mice, 24h prior to or immediately after AO (2.0ml/kg) exposure
      showed significant decrease in tail moment (70-72%), tail length (37-44%), and
      tail DNA (49-53%) in bone marrow cells. Single or multiple doses of antioxidants
      given after 24h of AO exposure resulted in substantial (P<0.05) decrease in all
      the parameters of comet assay in bone marrow cells. Single dose of antioxidants
      given either 24h prior to or immediately after sanguinarine (21.6mg/kg) exposure
      caused significant decrease in tail moment (56-62%), tail length (69%) and tail
      DNA (34-42%) in bone marrow cells of mice. Single or multiple doses of
      antioxidants given after 24h of sanguinarine treated resulted in decrease in tail
      moment (50-71%), tail length (54-63%) and tail DNA (29-43%) in bone marrow cells.
      Similar protective response of combination of antioxidants was observed in blood
      cells of mice treated either with AO or sanguinarine alkaloid. Further, the
      frequency of bone marrow and blood cells in Olive tail moment category of 8 and
      onwards were found to be substantially reduced in antioxidants treated animals as
      compared to respective AO or sanguinarine exposed mice. Based on these results,
      it can be suggested that a combination of riboflavin and alpha-tocopherol
      provides protection against AO and sanguinarine induced genotoxicity.

PMID- 16458424
TI  - Cytoplasmic phospholipase A2 expression in human colon adenocarcinoma is
      correlated with cyclooxygenase-2 expression and contributes to prostaglandin E2
      production.
AB  - Cytoplasmic phospholipase A2 (cPLA2) has a key role in prostaglandin production.
      The role of cPLA2 in intestinal tumorigenesis has been suggested, however,
      contradictory data are found in the literature. We evaluated cPLA2 and
      cyclooxygenase-2 (COX-2) protein expression in 65 colon carcinomas by
      immunohistochemistry, and in eight colorectal cancer cell lines by Western Blot.
      PGE2 production was evaluated by enzyme-immunoassay in the cell lines. We
      demonstrate that cPLA2 is overexpressed in approximately 50% of colon cancers and
      cell lines. cPLA2 expression is correlated with COX-2 expression. Both cPLA2 and
      COX-2 expressions are important in regard to PGE2 production. Our data suggest
      that cPLA2 might be involved in colon tumor development.

PMID- 16458425
TI  - Methylation of apoptosis related genes in the pathogenesis and prognosis of
      prostate cancer.
AB  - We investigated aberrant methylation in 101 prostate cancers(PCa) and 32
      histologically normal prostate tissues. We focused on genes largely in the
      apoptotic pathway. Methylation frequencies of the genes were Reprimo, 54%; TMS1,
      47%; DcR1, 45%; RRAD, 37%; DcR2, 37%; CRBP1, 34%; HPP1, 32%; RIZ1, 31%;
      DRM/Gremlin, 21%; SOCS1, 20%; DR4, 5%; DR5, 1%. Methylation of Reprimo and TMS1
      correlate with preoperative serum prostate-specific antigen. Methylation of TMS1,
      DcR1, DcR2, and CRBP1 correlate with Gleason score. Methylation of TMS1 and
      unmethylation of both DcR1 and DcR2 correlate with poorer disease free survival
      by univariate and multivariate analyses. Our data suggest that methylation of
      multiple genes may be involved in pathogenesis and correlate with prognosis of
      PCa.

PMID- 16458426
TI  - The repressive effect of green tea ingredients on amyloid precursor protein (APP)
      expression in oral carcinoma cells in vitro and in vivo.
AB  - In a hamster model of N-methyl-N-benzylnitrosamine (MBN)-induced oral
      carcinogenesis, the incidence of buccal pouch (HBP) carcinomas in MBN-treated
      hamsters (17.8+/-7.5) was significantly higher than MBN-treated hamsters given
      tea (10.8+/-3.9) (P<0.05). Amyloid precursor protein (APP) expression was also
      significantly increased in MBN-induced HBP carcinomas but was significantly
      reduced by tea intake (P<0.0001). Furthermore, APP expression and secretion by
      OECM-1 oral squamous cell carcinoma cells was inhibited by a major polyphenolic
      ingredient of green tea, (-)-epigallocatechin gallate, in a dose-dependent
      manner. Thus, APP might promote oral carcinogenesis, whereas green tea
      ingredients might diminish it by down-regulating APP.

PMID- 16458427
TI  - SRC-3/AIB1 protein and gene amplification levels in human esophageal squamous
      cell carcinomas.
AB  - It has been suggested that the steroid receptor coactivatior-3 (SRC-3) gene, also
      known as AIB1, ACTR, RAC3, p/CIP and TRAM-1, located at 20q12, plays an oncogenic
      role in several types of human cancers. In this study, we examined the encoded
      protein expression of SRC-3 and its copy number in 221 human esophageal squamous
      cell carcinomas (ESCCs). In this ESCC series, the overexpression and increased
      copy number of SRC-3 gene was detected in 46 and 13% of ESCCs, respectively. In
      addition, overexpression of SRC-3 was observed more frequently in primary ESCCs
      in late T stages (T3/T4) than that in earlier T1/T2 stages (P<0.05), but no
      significant association of expression of SRC-3 and status of lymph node
      metastases was observed (P>0.05). These results suggest that overexpression of
      SRC-3, caused by gene amplification/gain or other molecular mechanisms, might
      provide a selective advantage for the development and local invasion of certain
      subsets of ESCC. In addition, a significant correlation (P<0.05) of
      overexpression of SRC-3 with increased cell proliferation (through detection of
      Ki-67 expression) was observed in these ESCCs. These findings suggest a potential
      role of SRC-3 in the control of ESCC cell proliferation; such may be responsible,
      at least in part, for tumorigenesis and/or progression of ESCC.

PMID- 16458428
TI  - Allelic effects of mouse Pas1 candidate genes in human lung cancer cell lines.
AB  - Four of the six genes constituting the mouse Pulmonary adenoma susceptibility 1
      (Pas1) locus haplotype carry amino acid variants: Lrmp, Casc1, Ghiso, and Lmna
      rs1. In vitro colony formation assay of human lung cancer cell lines A549 and NCI
      H520 transfected with the allelic variants of the four genes revealed allele
      specific modulations of colony numbers by Lmna-rs1 and Casc1, but not by Lrmp or
      Ghiso. In A549 and NCI-H520 cells, the A/J allele of Lmna-rs1 produced
      approximately 4- and approximately 2-fold, respectively, more transfectants than
      did the C57BL/6J allele, whereas the A/J allele of Casc1 produced approximately 6
      and approximately 5-fold fewer transfectants, respectively, as compared to the
      C57BL/6J allele. Inhibition of clonogenicity by allelic forms of Pas1 candidate
      genes was not mediated by induction of apoptosis. These findings provide evidence
      that allelic variants of mouse Pas1 candidate genes differentially modulate
      growth of human cancer cells.

PMID- 16458429
TI  - Methyl protodioscin induces G2/M cell cycle arrest and apoptosis in HepG2 liver
      cancer cells.
AB  - Methyl protodioscin (NSC-698790) is one of the main bioactive components in the
      traditional Chinese medicine Dioscorea collettii var. hypoglauca (Dioscoreaceae).
      In this study, we investigated the anti-proliferative effect of methyl
      protodioscin on the HepG2 cells and the mechanism of the induced cytotoxicity.
      Treatment of methyl protodioscin resulted in G2/M arrest and apoptosis in HepG2
      cells. These effects were attributed to down-regulation of Cyclin B1 and the
      signaling pathways leading to up-regulation of Bax and down-regulation of BCL2,
      suggesting that methyl protodioscin may be a novel anti-mitotic agent.

PMID- 16458431
TI  - Clinical Sarcocystis neurona, Sarcocystis canis, Toxoplasma gondii, and Neospora
      caninum infections in dogs.
AB  - Sarcocystis neurona, Sarcocystis canis, Toxoplasma gondii, and Neospora caninum
      are related apicomplexans that can cause systemic illness in many species of
      animals, including dogs. We investigated one breeder's 25 Basset Hounds for these
      infections. In addition, tissues from dogs and other non-canine hosts previously
      reported as S. canis infections were studied retrospectively. Schizonts
      resembling those of S. neurona, and recognized by polyclonal rabbit anti-S.
      neurona antibodies, were found in six of eight retrospective cases, as well as in
      two additional dogs (one Basset Hound, one Springer Spaniel) not previously
      reported. S. neurona schizonts were found in several tissues including the
      central nervous system, lungs, and kidneys. Fatal toxoplasmosis was diagnosed in
      an adult dog, and neosporosis was diagnosed in an adult and a pup related to the
      one diagnosed with S. neurona. No serological reactivity to S. neurona antibodies
      occurred when S. canis-like liver schizonts were retrospectively assayed from two
      dogs, a dolphin, a sea lion, a horse, a chinchilla, a black or either of two
      polar bears. Sequencing conserved (18S) and variable (ITS-1) portions of nuclear
      ribosomal DNA isolated from the schizont-laden liver of a polar bear
      distinguished it from all previously characterized species of Sarcocystis. We
      take this genetic signature as provisionally representative of S. canis, an
      assumption that should be tested with future sequencing of similar liver
      infections in other mammalian hosts. These findings further extend the
      uncharacteristically broad intermediate host range for S. neurona, which also
      causes a neurologic disease in cats, mink, raccoons, skunks, Pacific harbor
      seals, ponies, zebras, lynxes, and sea otters. Further work is necessary to
      delineate the causative agent(s) of other cases of canine sarcocystosis, and in
      particular to specify the attributes of S. canis, which corresponds
      morphologically to infections reported from wide range of terrestrial and marine
      mammals.

PMID- 16458432
TI  - Galectin-3 in macrophage-like cells exposed to immunomodulatory drugs.
AB  - During the last few decades, the effects of immunomodulatory drugs on numerous
      molecules and biological processes have been widely studied. Nevertheless, the
      relationship between immunomodulatory drugs and lectin expression/function is
      still to be elucidated. In this study, we used THP-1-derived macrophages to
      investigate the effects of non-steroidal anti-inflammatory drugs (aspirin and
      indomethacin) and glucocorticoids (hydrocortisone and dexamethasone) on galectin
      3, a multifunctional beta-galactoside binding lectin, which in general acts as a
      strong pro-inflammatory signal. The results showed that all immunomodulatory
      drugs applied in clinically relevant doses affect both the gene (LGALS3) and
      protein expression level of galectin-3. The provoked changes on protein level are
      qualitatively and quantitatively different comparing to the effects on galectin-3
      mRNA level, and depend on the differentiation state of the cell, drug type and
      applied concentration as well as on time of the exposure. Our data revealed
      galectin-3 as a new target molecule of immunomodulatory drugs, thus suggesting an
      additional pathway of their action on immune response.

PMID- 16458430
TI  - The XPD Asp312Asn and Lys751Gln polymorphisms, corresponding haplotype, and
      pancreatic cancer risk.
AB  - We evaluated the association between the XPD exon 10 Asp(312)Asn and exon 23
      Lys(751)Gln polymorphisms and the risk of pancreatic cancer in a hospital-based
      study of 344 patients and 386 controls frequency matched by age, gender, and
      race. Stratified analyses showed ever smokers carrying the Asn(312)Asn genotype
      had a significantly reduced risk when compared with those carrying the (312)Asp
      allele (OR=0.46, 95% confidence interval 0.24-0.88) (P for interaction=0.03). The
      (312)Asp-(751)Gln was identified as the putative at risk haplotype. Our study
      shows that the XPD gene polymorphism could be a genetic risk modifier for smoking
      related pancreatic cancer.

PMID- 16458433
TI  - Caissarolysin I (Bcs I), a new hemolytic toxin from the Brazilian sea anemone
      Bunodosoma caissarum: purification and biological characterization.
AB  - Two cationic proteins, C1 and C3, were purified to homogeneity from the hemolytic
      fraction of the venom of Bunodosoma caissarum sea anemone. The purification
      processes employed gel filtration followed by ion exchange chromatography, being
      the purity and molecular mass confirmed by SDS-PAGE and mass spectrometry.
      Protein C1 represented the second major peak of the hemolytic fraction and was
      previously believed to be a cytolysin belonging to a new class of hemolysins. The
      C1 protein has a molecular mass of 15495 Da and was assayed for hemolysis, PLA2
      activity and acute toxicity in crabs and mice, showing no activity in these
      assays. It has an amino terminal with no similarity to all known hemolysins and,
      therefore, should not be considered a toxin, being its function completely
      unknown. The protein C3 (19757 Da), that also lacks PLA2 activity, was recognized
      by antiserum against Eqt II and presented high hemolytic activity to human
      erythrocytes (ED50 of 0.270 microg/ml), being named Caissarolysin I (Bcs I). Its
      activity was inhibited by pre-incubation with sphingomyelin (SM) and also when in
      presence of erythrocytes pre-treated with the SMase P2, a phospholipase D from
      the brown spider Loxosceles intermedia, indicating that SM is the main target of
      Bcs I. Caissarolysin I is the first hemolysin purified from a sea anemone
      belonging to the genus Bunodosoma and belongs to the Actinoporin family of sea
      anemone hemolysins.

PMID- 16458434
TI  - Hormone refractory prostate cancer: Management and advances.
AB  - Effective therapeutic options have not existed for prostate cancer progressing
      after androgen deprivation therapy until very recently. Secondary hormonal
      manipulations offer marginal benefits. Docetaxel based chemotherapy has been
      demonstrated to extend survival and change the natural history of the disease in
      two large randomized trials. These studies have provided the impetus to combine
      docetaxel with novel biologic agents to further consolidate the gains in long
      term outcome. With the arrival of exciting agents including vaccines, monoclonal
      antibodies, bone-targeted drugs, antisense oligonucleotides, anti-angiogenic
      drugs and small molecule receptor tyrosine kinase inhibitors, the future
      treatment of prostate cancer appears promising.

PMID- 16458435
TI  - Forebrain projections of tuberoinfundibular peptide of 39 residues (TIP39)
      containing subparafascicular neurons.
AB  - Neurons containing tuberoinfundibular peptide of 39 residues (TIP39) constitute a
      rostro-caudally elongated group of cells in the posterior thalamus. These neurons
      are located in the rostral part of the subparafascicular nucleus and in the
      subparafascicular area, caudally. Projections of the caudally located TIP39
      neurons have been previously identified by their disappearance following lesions.
      We have now mapped the projections of the rat rostral subparafascicular neurons
      using injections of the anterograde tracer biotinylated dextran amine and the
      retrograde tracer cholera toxin B subunit, and confirmed the projections from
      more caudal areas previously inferred from lesion studies. Neurons from both the
      rostral subparafascicular nucleus and the subparafascicular area project to the
      medial prefrontal, insular, ecto- and perirhinal cortex, nucleus of the diagonal
      band, septum, central and basomedial amygdaloid nuclei, fundus striati, basal
      forebrain, midline and intralaminar thalamic nuclei, hypothalamus, subthalamus
      and the periaqueductal gray. The subparafascicular area projects more densely to
      the amygdala and the hypothalamus. In contrast, only the rostral part of the
      subparafascicular nucleus projects significantly to the superficial layers of
      prefrontal, insular, ectorhinal and somatosensory cortical areas. Double labeling
      showed that anterogradely labeled fibers from the rostral part of the
      subparafascicular nucleus contain TIP39 in many forebrain areas, but do not in
      hypothalamic areas. Injections of the retrograde tracer cholera toxin B subunit
      into the lateral septum and the fundus striati confirmed that they were indeed
      target regions of both the rostral subparafascicular nucleus and the
      subparafascicular area. In contrast, TIP39 neurons did not project to the
      anterior hypothalamic nucleus. Our data provide an anatomical basis for the
      potential involvement of rostral subparafascicular neurons in limbic and
      autonomic regulation, with TIP39 cells being major subparafascicular output
      neurons projecting to forebrain regions.

PMID- 16458436
TI  - Sex differences in the hilar mossy cells of the guinea-pig before puberty.
AB  - Numerous sex differences have been detected in the morphology of the dentate and
      hippocampal neurons and hippocampus-dependent memory functions. The aim of the
      present study was to ascertain whether the mossy cells, an interneuron population
      forming a recurrent excitatory circuit with the dentate granule cells, are
      sexually dimorphic. The brains of juvenile (15-16 days old) and peripubescent (45
      46 days old) male and female guinea-pigs were Golgi-Cox stained. Mossy cells were
      sampled from the hilus in the septal third of the dentate gyrus and their
      dendritic tree and somata were analyzed. The analysis was separately conducted on
      mossy cells with soma located in the portions of the hilus that face the upper
      blade (upper hilus) and lower blade (lower hilus), respectively. The mossy cells
      in the upper hilus were found to be sexually dimorphic in both juvenile and
      peripubescent animals. At both ages females had a larger dendritic tree than
      males. This difference was due to a greater mean branch length and, in
      peripubescent animals, also to a greater number of branches. In juvenile males,
      the spines on the proximal dendrites (thorny excrescences) had a greater density
      than in females. No differences in spine density were present in peripubescent
      animals. Unlike the mossy cells in the upper hilus, the mossy cells in the lower
      hilus showed very few sex differences in juvenile animals and no differences in
      peripubescent animals. The few differences favored females, that had more
      proximal branches and a greater spine density on the distal dendrites than males.
      The results show that the mossy cells of the guinea-pig are sexually dimorphic
      prior to puberty. Extending a previous investigation, the present data provide
      evidence that sex differences are mainly confined to the dentate region
      corresponding to the upper blade and upper hilus. The observed segregation of the
      sexual dimorphism in the upper blade/upper hilus suggests that this region might
      underlie the sexual dimorphism in hippocampus-dependent memory functions.

PMID- 16458437
TI  - Tachykinins are involved in local reflex modulation of vagally mediated striated
      muscle contractions in the rat esophagus via tachykinin NK1 receptors.
AB  - The objective of the present study was to investigate the hypothesis of the
      presence of a local neural reflex modulating the vagally mediated contractions of
      striated muscle in the rat esophagus and to determine the possible involvement of
      tachykinins in such a local neural reflex. Electrical stimulation of the vagus
      nerve evoked twitch contractile responses that were abolished by d-tubocurarine
      (5 microM). Capsaicin (1-100 microM) inhibited the vagally mediated twitch
      contractions o f the normal rat esophageal preparations concentration-dependently
      but not those of the neonatally capsaicin-treated ones. NG-nitro-L-arginine
      methyl ester (100 microM), a nitric oxide synthase inhibitor, blocked the
      inhibitory effect of capsaicin and exogenous application of a nitric oxide donor
      (1 mM) inhibited the vagally mediated twitch contractions. Capsaicin suppressed
      acetylcholine release from the normal rat esophageal segments evoked by vagus
      nerve stimulation but not that from the neonatally capsaicin-treated ones. A
      selective tachykinin NK1 receptor antagonist (0.1 or 1 microM) attenuated the
      inhibitory effect of capsaicin. However, antagonists of tachykinin NK2,
      tachykinin NK3 and calcitonin gene-related peptide receptors (1 microM) did not
      have any effect. A tachykinin NK1 receptor agonist (1 or 5 microM) inhibited the
      vagally mediated twitch contractions, which was prevented by NG-nitro-L-arginine
      methyl ester (100 microM). These data suggest that the rat esophagus might have a
      local neural reflex inhibiting the vagally mediated striated muscle motility,
      which consists of capsaicin-sensitive sensory neurons and myenteric nitrergic
      neurons, and that tachykinins might be involved in the neural reflex through
      tachykinin NK1 receptors.

PMID- 16458438
TI  - Memory trace of motor learning shifts transsynaptically from cerebellar cortex to
      nuclei for consolidation.
AB  - Adaptation of ocular reflexes is a prototype of motor learning. While the
      cerebellum is acknowledged as the critical site for motor learning, the
      functional differences between the cerebellar cortex and nuclei in motor memory
      formation are not precisely known. Two different views are proposed: one that the
      memory is formed within the cerebellar flocculus, and the other that the memory
      is formed within vestibular nuclei. Here we developed a new paradigm of long-term
      adaptation of mouse horizontal optokinetic response eye movements and examined
      the location of its memory trace. We also tested the role of flocculus and
      inferior olive in long-term adaptation by chronic lesion experiments. Reversible
      bilateral flocculus shutdown with local application of 0.5 microl-5% lidocaine
      extinguished the memory trace of day-long adaptation, while it very little
      affected the memory trace of week-long adaptation. The responsiveness of
      vestibular nuclei after week-long adaptation was examined by measuring the
      extracellular field responses to the electrical stimulation of vestibular nerve
      under trichloroacetaldehyde anesthesia. The amplitudes and slopes of evoked
      monosynaptic field response (N1) of week-long adapted mice were enhanced around
      the medial vestibular nucleus compared with those of control mice. Chronic
      flocculus or inferior olive lesions abolished both day and week-long adaptations.
      These results suggest that the functional memory trace of short-term adaptation
      is formed initially within the cerebellar cortex, and later transferred to
      vestibular nuclei to be consolidated to a long-term memory. Both day and week
      long adaptations were markedly depressed when neural nitric oxide was
      pharmacologically blocked locally and when neuronal nitric oxide synthase was
      ablated by gene knockout, suggesting that cerebellar long-term depression
      underlies both acquisition and consolidation of motor memory.

PMID- 16458440
TI  - Excitatory amino acid receptors in the periaqueductal gray mediate the
      cardiovascular response evoked by activation of dorsomedial hypothalamic neurons.
AB  - Neurons in the region of dorsomedial hypothalamus are involved in the
      organization of the physiological responses to emotional stress. We have recently
      shown that the cardiovascular response evoked by activation of dorsomedial
      hypothalamus neurons is largely dependent on a synaptic relay with the
      lateral/dorsolateral periaqueductal gray region. In this study, we aimed to
      investigate whether excitatory amino acid receptors at the lateral/dorsolateral
      periaqueductal gray region are involved in mediating the response evoked by
      activation of dorsomedial hypothalamus neurons. In conscious rats, the
      cardiovascular effects produced by microinjection of GABA(A) receptor antagonist,
      bicuculline methiodide into the dorsomedial hypothalamus were evaluated before
      and after injection of different excitatory amino acid antagonists into
      lateral/dorsolateral periaqueductal gray region. Pretreatment of
      lateral/dorsolateral periaqueductal gray region with the non-selective ionotropic
      excitatory amino acid receptor antagonist kynurenic acid or with the N-methyl-D
      aspartate receptor-selective antagonist, MK-801, largely reduced the tachycardic
      and pressor effects evoked by activation of dorsomedial hypothalamus neurons by
      bicuculline methiodide microinjection (heart rate 90 and 74%; blood pressure 81
      and 84%, respectively). The non-N-methyl-D-aspartate receptor-selective
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, did not alter the cardiovascular
      response evoked by dorsomedial hypothalamus activation. In an additional series
      of experiments, microinjection of the N-methyl-D-aspartate receptor agonist, N
      methyl-D-aspartate, into the lateral/dorsolateral periaqueductal gray region,
      evoked an increase in heart rate and a pressor response that was accompanied by
      an increase in locomotor activity. These effects were not altered by pretreatment
      of lateral/dorsolateral periaqueductal gray region neurons with 6-cyano-7
      nitroquinoxaline-2,3-dione but were completely abolished by MK-801. Altogether,
      these findings indicate that the cardiovascular response evoked by dorsomedial
      hypothalamus activation involves a synaptic relay at the lateral/dorsolateral
      periaqueductal gray region that is mediated at least in large part by excitatory
      amino acid receptors, possibly N-methyl-D-aspartate receptors.

PMID- 16458439
TI  - Long-term fate of neural precursor cells following transplantation into
      developing and adult CNS.
AB  - Successful strategies for transplantation of neural precursor cells for
      replacement of lost or dysfunctional CNS cells require long-term survival of
      grafted cells and integration with the host system, potentially for the life of
      the recipient. It is also important to demonstrate that transplants do not result
      in adverse outcomes. Few studies have examined the long-term properties of
      transplanted neural precursor cells in the CNS, particularly in non-neurogenic
      regions of the adult. The aim of the present study was to extensively
      characterize the fate of defined populations of neural precursor cells following
      transplantation into the developing and adult CNS (brain and spinal cord) for up
      to 15 months, including integration of graft-derived neurons with the host.
      Specifically, we employed neuronal-restricted precursors and glial-restricted
      precursors, which represent neural precursor cells with lineage restrictions for
      neuronal and glial fate, respectively. Transplanted cells were prepared from
      embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the
      marker gene human placental alkaline phosphatase to achieve stable and reliable
      graft tracking. We found that in both developing and adult CNS grafted cells
      showed long-term survival, morphological maturation, extensive distribution and
      differentiation into all mature CNS cell types (neurons, astrocytes and
      oligodendrocytes). Graft-derived neurons also formed synapses, as identified by
      electron microscopy, suggesting that transplanted neural precursor cells
      integrated with adult CNS. Furthermore, grafts did not result in any apparent
      deleterious outcomes. We did not detect tumor formation, cells did not localize
      to unwanted locations and no pronounced immune response was present at the graft
      sites. The long-term stability of neuronal-restricted precursors and glial
      restricted precursors and the lack of adverse effects suggest that
      transplantation of lineage-restricted neural precursor cells can serve as an
      effective and safe replacement therapy for CNS injury and degeneration.

PMID- 16458441
TI  - Muller glial cells express nestin coupled with glial fibrillary acidic protein in
      experimentally induced glaucoma in the rat retina.
AB  - This study was aimed to investigate reactive changes of Muller glial cells in
      rats subjected to experimentally induced glaucoma. In the latter, it is well
      documented that elevated intraocular pressure leads to the loss of ganglion cells
      as confirmed in this study. The present results have shown that Muller glial
      cells as well as astrocytes closely associated with the ganglion cells reacted
      vigorously to increased intraocular pressure as manifested by the induced and
      upregulated expression of nestin and glial fibrillar acidic protein. A major
      finding in glaucomatous rats was the induced expression of nestin together with
      glial fibrillar acidic protein with the rise of the intraocular pressure
      beginning at 2 h. The marked nestin expression appeared to be most intense at 1
      week after operation and was sustained at 3 weeks. Induced nestin expression in
      Muller glial cells was demonstrated unequivocally in whole-mount preparation of
      the retina. In the same tissue preparation, nestin expression was also detected
      in some astrocytes. Western blotting analysis confirmed a marked increase in
      expression of nestin and glial fibrillar acidic protein. Present results suggest
      that nestin as well as glial fibrillar acidic protein is a useful biomarker for
      retina injury. The induced expression of these intermediate filament proteins in
      Muller glial cells especially at their end-feet and also in some astrocytes
      adjoining the neuronal injury suggests a potential neuroprotective mechanism in
      response to acute rise in intraocular pressure resulting in neuronal
      degeneration.

PMID- 16458442
TI  - A functional magnetic resonance imaging study of the effects of pergolide, a
      dopamine receptor agonist, on component processes of working memory.
AB  - Working memory is an important cognitive process dependent on a network of
      prefrontal and posterior cortical regions. In this study we tested the effects of
      the mixed D1-D2 dopamine receptor agonist pergolide on component processes of
      human working memory using functional magnetic resonance imaging (fMRI). An event
      related trial design allowed separation of the effects on encoding, maintenance,
      and retrieval processes. Subjects were tested with spatial and object memoranda
      to investigate modality-specific effects of dopaminergic stimulation. We also
      measured baseline working memory capacity as previous studies have shown that
      effects of dopamine agonists vary with working memory span. Pergolide improved
      reaction time for high-span subjects and impaired reaction time for low-span
      subjects. This span-dependent change in behavior was accompanied by span
      dependent changes in delay-related activity in the premotor cortex. We also found
      evidence for modality-specific effects of pergolide only during the response
      period. Pergolide increased activity for spatial memoranda and decreased activity
      for object memoranda in task-related regions including the prefrontal and
      parietal cortices.

PMID- 16458444
TI  - Isolated (localized) idiopathic granulomatous (giant cell) vasculitis in an
      intramuscular lipoma.
AB  - Isolated (localized) idiopathic granulomatous vasculitis (IGV) is an uncommon,
      heterogeneous, and poorly defined group of disorders characterized by
      infiltration of the arterial wall caused by compactly grouped mononuclear
      phagocytes, with or without giant cells, in segmental distribution. We report on
      a 55-year-old woman with IGV limited to an intramuscular lipoma of the left
      thigh. The vasculitis was identified incidentally upon microscopic examination of
      the removed tumor. The IGV was centered on two medium-sized arteries, accompanied
      by narrowing of the lumens, and not associated with secondary changes such as
      infart or postinfart fibrosis. The inflammatory infiltrate was rich in T
      lymphocytes and macrophages, with the presence of giant cells. The patient was
      asymptomatic and well in a follow-up period of 2 months, during which she was not
      treated. To our knowledge, this is the first report of lipoma involvement in
      localized IGV. It is important to distinguish cases of isolated intratumorous IGV
      from systemic disease, because the latter implies a poor prognosis and requires
      an aggressive treatment.

PMID- 16458445
TI  - Comparison of immunohistological parameters in primary breast cancers and
      corresponding locoregional recurrences.
AB  - Biological changes in breast cancers during tumor progression can affect
      therapeutic parameters, such as hormone receptors. We studied a series of primary
      tumors and the matching recurrent lesions to analyze the frequency of this
      phenomenon and the impact on disease-free interval. The expression of ER, PgR, c
      erbB2, CD44v6, and p53 in the primary and the locoregional tumor was analyzed in
      70 patients with recurrent breast cancer. Antigen expression correlated well
      between the primary and the matching recurrent tumor for all antigens under
      study. However, hormone receptor expression was lost in more than 50% of the
      cases, without significant impact on the disease-free survival interval. The
      disease-free interval was significantly longer for PgR-positive primary tumors,
      but did not depend on the ER status. The expression or changes of c-erbB2,
      CD44v6, and p53 were not related to the recurrence-free time intervals.
      Therefore, for treatment, it seems important to consider a possible loss of
      hormone receptors during tumor progression.

PMID- 16458446
TI  - Role of intracanalicular volumetric and dosimetric parameters on hearing
      preservation after vestibular schwannoma radiosurgery.
AB  - PURPOSE: To analyze the relationship between hearing preservation after gamma
      knife radiosurgery (GKR) for vestibular schwannoma (VS) and some volumetric and
      dosimetric parameters of the intracanalicular components of VS. METHODS AND
      MATERIALS: This study included 82 patients with a VS treated by GKR; all patients
      had no NF2 disease, a Gardner-Robertson hearing class 1-4 before treatment, a
      marginal dose of 12 Gy, and a radiologic and audiologic follow-up > or =1 year
      post-GKR. The volume of both the entire tumor and the intracanalicular part of
      the tumor and the mean and integrated dose of these two volumes were correlated
      to the auditory outcomes of patients. RESULTS: At last hearing follow-up, 52
      patients had no hearing worsening, and 30 patients had an increase of > or =1
      class on Gardner-Robertson classification. We found that hearing preservation
      after GKR is significantly correlated with the intracanalicular tumor volume, as
      well as with the integrated dose delivered to the intracanalicular tumor volume.
      CONCLUSIONS: Some volumetric and dosimetric parameters of the intracanalicular
      part of the tumor influence hearing preservation after GKR of VS. Consequently,
      we advise the direct treatment of patients with preserved functional hearing and
      a VS including a small intracanalicular volume.

PMID- 16458447
TI  - High-dose proton beam therapy for Stage I non-small-cell lung cancer.
AB  - PURPOSE: To evaluate retrospectively the safety and efficacy of high-dose proton
      beam therapy (PBT) for Stage I non-small-cell lung cancer (NSCLC). METHODS AND
      MATERIALS: Between 1999 and 2003, 37 patients were treated in our institution.
      The indications for PBT were pathologically proven NSCLC, clinical Stage I, tumor
      size < or =5 cm, medically inoperable or refusal of surgery, and written informed
      consent. A total dose of 70-94 Gy(E) was delivered in 20 fractions (3.5-4.9 Gy(E)
      per fraction). RESULTS: Patient characteristics (number of patients) were as
      follows: Stage IA/IB, 17 of 20; medically inoperable/refusal of surgery, 23/14;
      total dose 70/80/88/94 Gy(E), 3/17/16/1. With a median follow-up period of 24
      months, the 2-year local progression-free and overall survival rates were 80% and
      84%, respectively. The 2-year locoregional relapse-free survival rates in Stage
      IA and Stage IB were 79% and 60%, respectively. No serious acute toxicity was
      observed. Late Grades 2 and 3 pulmonary toxicities were observed in 3 patients
      each. Of these 6 patients, 5 had Stage IB disease. CONCLUSIONS: Proton beam
      therapy is a promising treatment modality for Stage I NSCLC, though locoregional
      relapse and late pulmonary toxicities in Stage IB patients were substantial.
      Further investigation of PBT for Stage I NSCLC is warranted.

PMID- 16458448
TI  - Analysis of TP53 gene mutations in human lung cancer: comparison of capillary
      electrophoresis single strand conformation polymorphism assay with denaturing
      gradient gel electrophoresis and direct sequencing.
AB  - INTRODUCTION: Automated capillary electrophoresis single strand conformation
      polymorphism (CE-SSCP), denaturant gradient gel electrophoresis (DGGE), and
      direct sequencing were compared to investigate the benefits and sensitivity of
      each of the methods for detection of unknown TP53 mutations in human lung cancer.
      METHODS: Twenty previously analyzed DNA samples from lung tumors were examined
      under dummy laboratory codes for occurrence of mutations of the TP53 gene.
      RESULTS: Mutations were found in 17 samples; 15 (88%) of them were detected by
      DGGE, 16 (94%) by CE-SSCP and 12 (71%) by direct sequencing. One of the two
      mutations that remained undetected in DGGE was in fact outside the sequence area
      covered by DGGE screening, thus rendering DGGE and CE-SSCP equally efficient in
      mutation detection. Direct sequencing performed less well in finding mutations
      than the two other assays, as also shown previously. CONCLUSION: The study showed
      that CE-SSCP is a fast and highly reproducible method, which is considerably less
      laborious compared to DGGE, for screening of unknown TP53 mutations.

PMID- 16458449
TI  - Primary care patients' understanding of colorectal cancer screening.
AB  - PURPOSE: To determine the current level of awareness and understanding about
      colorectal cancer (CRC) and colorectal cancer screening (CRCS) among primary care
      patients in order to develop interventions to educate patients about options for
      CRCS, help them identify CRCS preferences and make informed choices about CRCS
      options. METHODS: During the spring of 2001 and 2003, two sets of focus groups
      with primary care patients were conducted at a large multi-specialty group
      practice in Houston, Texas. RESULTS: Participants (n = 42) in both sets of focus
      groups had low knowledge about CRC and expressed fear and embarrassment about CRC
      and CRCS. Attitudes towards the fecal occult blood test (FOBT) were mixed, with
      some participants considering it difficult to finish and others preferring the
      privacy it afforded. Some participants initially failed to recognize the
      difference between sigmoidoscopy (SIG) and colonoscopy (COL), and several
      endoscopy-specific barriers were identified such as fear of pain,
      embarrassment/humiliation, and dislike or fear of test preparation. Some
      participants felt that endoscopy was likely to be more effective than FOBT, and
      others clearly preferred COL to SIG. System-specific barriers to endoscopy (e.g.
      difficulty scheduling appointments and insurance coverage) were also identified.
      We found little change in the barriers reported by primary care patients, despite
      a two-year difference between focus groups. Participants also provided
      suggestions for improving CRCS including telephone, letters and/or email
      reminders from the clinic, videotapes and websites. CONCLUSIONS: Future
      interventions focused on improving informed decision-making by educating primary
      care patients about the risks and benefits of specific test options and about the
      importance of early detection of CRC could prove to be effective for increasing
      CRCS.

PMID- 16458450
TI  - The endothelial nitric oxide synthase Glu-298-Asp polymorphism and its mRNA
      expression in the peripheral blood of patients with prostate cancer and benign
      prostatic hyperplasia.
AB  - BACKGROUND: The endothelial nitric oxide synthase (ecNOS) has an important role
      in vascular development and in the carcinogenesis process of prostate cancer
      (PCa). The nitric oxide (NO) production may promote cancer progression by
      providing a selective growth advantage to tumor cells, by angiogenic stimulus and
      by direct DNA damage. METHODS: The present study aimed at evaluating the ecNOS
      Glu-298-Asp polymorphism by the PCR-RFLP technique, associating genotypes with
      gene expression levels and the tumor biomarker, Prostate Cancer Antigen (DD3),
      through semi-quantitative RT-PCR. Pre-surgical peripheral blood samples from 160
      patients were analyzed: 84 PCa, 11 prostate intraepithelial neoplasia (PIN) and
      65 benign prostatic hyperplasia (BPH). RESULTS: The GG and GT Glu-298-Asp
      genotypes were associated with positive DD3 expression in the peripheral blood,
      presenting a 3.32-fold higher risk of PCa occurrence. There was no association
      between genotypes and ecNOS mRNA expression levels; however, the presence of the
      G allele is closely related to the hematogenous dissemination event of tumoral
      cells, as evidenced by the DD3 positivity. The higher G allele frequency among
      pT3 and pT4 staged PCa patients suggests that this would be associated with
      advanced phenotypes of the disease and may also be contributing to higher NO
      levels, causing cancer progression. CONCLUSIONS: The G allele may have a
      secondary influence on the prostate cancer predisposition, but an essential role
      on the event of tumor cells hematogenous dissemination, probably due to the
      angiogenic stimulus.

PMID- 16458451
TI  - Immunomodulation with low dose levamisole in patients with colonic polyps.
AB  - BACKGROUND: Levamisole (LMS) has immunomodulatory activity, stimulates the immune
      system of healthy, normal volunteers and has been proposed previously as a colon
      cancer preventive agent. METHODS: Patients with a history of colonic polyps who
      are at increased risk of colon cancer received LMS in a placebo-controlled,
      double-blinded clinical trail with crossover design. Primary endpoints were
      immunologic and included flow cytometry of peripheral blood mononuclear cells
      (PBMCs), measurement of interferon-gamma copy number (IGCN) in PBMCs, and an ex
      vivo serum immune assay. RESULTS: No differences were seen in the expression of
      multiple antigens by flow cytometry pre- and post-LMS. The IGCN partitioned
      subjects into two distinct groups defined by a gamma-distribution which had a
      differential response to LMS. Those with low basal IGCN had a lower percentage of
      CD25 expressing PBMCs and responded to low dose LMS by producing more PBMC
      derived interferon-gamma and increasing the expression of CD25 and two NK cell
      markers, CD16 and CD56. In contrast, subjects with a high basal IGCN responded to
      low dose LMS with a reduction in PBMC-derived interferon-gamma and a decrease in
      the expression of CD25. CONCLUSIONS: In aggregate, these responses suggest that
      LMS may act as an immunostimulatory agent for one group, those with low basal
      IGCN, and as an immunosuppressive agent for the other. LMS may not be an optimal
      agent for most patients with colonic polyps and should be avoided in patients
      with normal immune function. IGCN may be useful as an immunologic surrogate
      endpoint biomarker in future cancer prevention trials with immunomodulatory
      agents.

PMID- 16458452
TI  - Health beliefs and practices related to breast cancer screening in Filipino,
      Chinese and Asian-Indian women.
AB  - BACKGROUND: Cultural-appropriate strategies can be designed to promote cancer
      screening if the unique needs and characteristics of ethnic groups are
      identified. Most of the data available for Asian immigrants living in the U.S.
      has been aggregated under the Asian-American/Pacific Islanders (AAPI) ethnic
      category. METHODS: A total of 125 women completed self-administered
      questionnaires that assessed screening practices (i.e. breast self-exam, clinical
      breast exam, and mammography), related beliefs and knowledge. This paper reports
      examined cancer-related practices and beliefs among three subgroups of Asian
      American women (47 Filipinos, 40 Chinese, and 38 Asian-Indians). RESULTS: The
      sample mean age was 50.2 years and majority of women (76%) were married. Their
      length of residence in the United States ranged from less than one year to 37
      years, with an average length of residence of 18 years. Results from two-way
      analyses of variance (ANOVAs) showed the strong influence of ethnicity on
      perceptions of susceptibility [F(2, 95) = 5.11, p = 0.01] and seriousness [F(2,
      99) = 4.85, p = 0.01] related to breast cancer, in addition to an interaction
      detected between ethnicity and income in terms of perceived barriers [F(5, 107) =
      3.04, p = 0.01]. The results also indicated that three common barriers were
      reported in all three ethnic groups, and three unique barriers were more
      frequently identified by Chinese (i.e. do not need mammogram if I feel ok [OR =
      5.450, 95%; CI = (1.643, 18.081)] and waiting time is too long [OR = 5.070, 95%;
      CI = (1.674, 15.351)]) and Asian-Indian women (i.e. do not know where to get a
      mammogram [OR = 9.237, 95%; CI = (3.153, 27.059)]). CONCLUSIONS: These findings
      can be used to develop interventions that are tailored to the special
      characteristics of immigrant women from different Asian groups.

PMID- 16458453
TI  - Colorectal cancer screening awareness in European primary care.
AB  - BACKGROUND: Adjustment for stage at diagnosis markedly reduces USA versus
      European colorectal cancer survival differences and a screening bias was
      therefore suspected. Moreover, little is known about colorectal cancer screening
      habits in European primary care and the history of guidelines implementation. The
      purpose of the study was to index the overall colorectal cancer screening
      attitudes of European physicians involved in primary care activities. METHODS: A
      systematic literature-search was performed in three major medical libraries:
      PubMed/MEDLINE, ISI web of science, and COCHRANE. RESULTS: We found only five
      eligible studies, but valuable data were presented only in four. Colorectal
      cancer screening was recommended by 65-95% of physicians, but the major part of
      them implemented it only among high-risk individuals; stool occult blood testing
      was advised by 42-83% and prescription of screening endoscopic modalities was
      inconsistent. Most European reports found were not eligible and were mainly
      focused on diagnostic delay in symptomatic subjects rather than on screening
      procedures among asymptomatic individuals. CONCLUSION: In comparison with
      European practice, colorectal cancer screening habits of American physicians are
      to a greater extent rational, evidence-based and well monitored and have a longer
      tradition in medical care thus allowing better prevention services for
      asymptomatic individuals.

PMID- 16458454
TI  - Passage of time leaves response-outcome associations intact.
AB  - The effect of the passage of time on the association between an instrumental
      response and its outcome was examined in three experiments with rats using
      outcome devaluation. In Experiments 1 and 2, rats were initially trained to make
      one pair of instrumental responses for different outcomes (e.g., lever press-
      >pellets and chain pull-->sucrose). Then, after a delay of several weeks, a
      second pair of responses for those different outcomes (e.g., nose poke-->pellets
      and handle pull-->sucrose) was trained in Experiment 1 but not in Experiment 2.
      One of the outcomes was then devalued and the responses were tested in
      extinction. There was no evidence that the passage of time eliminated the
      sensitivity of a response to a change in the value of its outcome. Experiment 3
      used the same design as Experiment 1 to examine the effect of the passage of time
      on extinguished instrumental responses. First, one pair of responses was trained
      with different outcomes and then extinguished prior to the training and
      subsequent extinction of a second pair of responses. After retraining both pairs
      of responses with a polycose outcome, one of the original outcomes was devalued.
      Each pair of responses was then tested in extinction. The results of the
      extinction tests revealed no evidence that the passage of time removed the
      sensitivity of an extinguished response to devaluation of its original outcome.
      These findings are consistent with other reports that the response-outcome
      association survives various response elimination techniques.

PMID- 16458455
TI  - Ephemeral profiles of prescription drug and formulation tampering: evolving
      pseudoscience on the Internet.
AB  - The magnitude of non-therapeutic use, or misuse of prescription pharmaceuticals
      now rivals that of illicit drug abuse. Drug and formulation tampering enables
      misusers to administer higher doses by intended and non-intended routes.
      Perceived motives appear to be a combination of interests in achieving a faster
      onset and enhancing psychoactive effects. Narcotic analgesics, stimulants, and
      depressants are widely sought, examined, and tampered with for recreational use.
      This review examines tampering methods reported on the Internet for selected
      pharmaceutical products. The Internet provides broad and varied guidance on
      tampering methods that are specific to drug classes and unique formulations.
      Instructions are available on crushing, separating, purifying and chemically
      altering specific formulations to allow changes in dosage, route of
      administration, and time course of effects. Many pharmaceutical formulations
      contain features that serve as "barriers" to tampering. The nature and
      effectiveness of formulation barriers vary widely with many being overcome by
      adventurous misusers. Examples of successes and failures in tampering attempts
      are frequently described on Internet sites that support recreational drug use.
      Successful tampering methods that have widespread appeal evolve into recipes and
      become archived on multiple websites. Examples of tampering methods include: (1)
      how to separate narcotic drugs (codeine, hydrocodone, oxycodone) from excipients
      and non-desirable actives (aspirin, acetaminophen, ibuprofen); (2) overcoming
      time-release formulations (beads, layers, matrices); (3) removal of active drug
      from high-dose formulations (patches, pills); (4) alteration of dosage forms for
      alternate routes of administration. The development of successful formulations
      that inhibit or prevent drug/formulation tampering with drugs of abuse should
      take into consideration the scope and practice of tampering methods available to
      recreational drug users on the Internet.

PMID- 16458456
TI  - Traffic safety for the cell: influence of cyclin-dependent kinase activity on
      genomic stability.
AB  - Genomic instability has long been considered a key factor in tumorigenesis.
      Recent evidence suggests that DNA damage may be widespread in early pre
      neoplastic states, with deregulation of cyclin-dependent kinase (Cdk) activity a
      driving force. Increased Cdk activity may critically reduce licensing of origins
      of DNA replication, drive re-replication, or mediate overexpression of checkpoint
      proteins, inducing deleterious cell cycle delay. Conversely, inhibition of Cdk
      activity may compromise replication efficiency, expression of checkpoint
      proteins, or activation of DNA repair proteins. These vital functions point to
      the impact of Cdk activity on the stability of the genome. Insight into these
      pathways may improve our understanding of tumorigenesis and lead to more rational
      cancer therapies.

PMID- 16458457
TI  - High risk of false positive results in a widely used diagnostic test for
      detection of the porcine reproductive and respiratory syndrome virus (PRRSV).
AB  - During 2003 and 2004, increasing numbers of positive PRRSV RT-PCR results were
      reported from herds negative for PRRSV infection. Interestingly, three herds
      represent nucleus herds with no animal contacts from outside and without clinical
      symptoms of PRRS until now. Since these positive results that were obtained using
      a PCR protocol adapted to routine laboratory conditions could not be reproduced
      with other PRRSV specific RT-PCRs, controlled negative and positive samples were
      used to examine this phenomenon. A RT-PCR assay for detection and differential
      diagnosis of the European and North American genotypes of the porcine
      reproductive and respiratory syndrome virus (PRRSV) according to the method
      previously published by Oleksiewicz et al. [Oleksiewicz, M.B., Botner, A.,
      Madsen, K.G., Storgaard, T., 1998. Sensitive detection and typing of porcine
      reproductive and respiratory syndrome virus by RT-PCR amplification of whole
      viral genes. Vet. Microbiol. 64, 7-22] was investigated in parallel to another
      recently published method [Pesch, S., 2003. Etablierung einer Nachweismethode fur
      die zwei Genotypen von dem porcine reproductive and respiratory syndrome virus
      (PRRSV) und ein Beitrag zu seiner molekularen Epidemiologie. Thesis, Institute of
      Virology, Faculty of Veterinary Medicine, University of Leipzig]. A panel of 228
      clinical samples sent in for PRRSV routine diagnostics served as test panel. It
      was found that both methods have similar analytical sensitivity. However, the
      primers published by Oleksiewicz were shown to yield a very high proportion of
      false positive results under routine diagnostic laboratory conditions, i.e. they
      resulted in RT-PCR products with non-PRRSV sequences, that were indistinguishable
      from truly positive reagents in standard gel electrophoresis settings. The reason
      for and possible implications of this finding as well as the risk of modifying
      published methods without control are discussed.

PMID- 16458458
TI  - A controlled trial of skin-to-skin contact in extremely preterm infants.
AB  - BACKGROUND: Extremely preterm birth, even in the absence of significant
      neurological impairment, is associated with altered pain responses and impaired
      memory and behaviour. Preterm birth increases the risk of maternal depression and
      may impede the development of the mother-infant relationship, factors that in
      turn are also associated with impaired infant outcome. Mother-infant skin-to-skin
      contact has been recommended as a simple means of ameliorating these effects.
      METHODS: We conducted a pragmatic, prospective, controlled, intention-to-treat
      trial in two neonatal intensive care units. Infants born below 32 weeks gestation
      were recruited within the first week after birth and assigned to a control group
      receiving standard care, or an intervention group in which mothers were
      encouraged to provide a session of skin-to-skin contact once daily for 4 weeks.
      We assessed infant behaviour at time of discharge from hospital, responses to
      immunisation at 4 and 12 months of age, and memory, behaviour and development at
      1 year corrected (postmenstrual) age. Indices of maternal depression, stress,
      anxiety, lactation performance and infant interaction were assessed at time of
      infant discharge, 4 months and 1 year. RESULTS: No significant difference was
      identified in any infant or maternal measure at any time point. CONCLUSIONS:
      Mother-infant skin-to-skin contact after extremely preterm birth results in
      neither benefit nor adverse consequences. Although there is no reason to dissuade
      mothers who wish to provide STS contact, we are unable to recommend resource
      allocation for the implementation of STS programmes for extremely preterm infants
      in a neonatal intensive care unit setting.

PMID- 16458459
TI  - Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl
      phthalate in fetal rat testis.
AB  - Phthalates are widely used as plasticizers in various consumer products and
      building materials. Some of the phthalates are known to interfere with male
      reproductive development in rats, and di-n-butyl phthalate (DBP), diethylhexyl
      phthalate (DEHP) and butyl benzyl phthalate (BBP) were recently banned for use in
      toys in the EU mainly due to their reproductive toxicity. Diisobutyl phthalate
      (DiBP) has similar structural and application properties as DBP, and is being
      used as a substitute for DBP. However, knowledge on male reproductive effects of
      DiBP in experimental animals is lacking. METHODS: In the current study, four
      groups of pregnant Wistar rats were exposed to either 0mg/kg bw/day or 600 mg/kg
      bw/day of DiBP from gestation day (GD) 7 to either GD 19 or GD 20/21. Male
      offspring was examined at GD 19 or GD 20/21 for effects on testicular
      testosterone production and testicular histopathology. Changes in anogenital
      distance (AGD) were evaluated as an indication of feminisation of males. RESULTS:
      Anogenital distance was statistically significantly reduced at GD 20/21 together
      with reductions in testicular testosterone production and testicular testosterone
      content. Histopathological effects (Leydig cell hyperplasia, Sertoli cell
      vacuolisation, central location of gonocytes and presence of multinuclear
      gonocytes) known for DBP and DEHP were observed in testes of DiBP-exposed animals
      at GD 20/21. Additionally, immunohistochemical expression of P450scc and StAR
      proteins in Leydig cells was reduced by DiBP. At GD 19, these effects on
      anogenital distance, testosterone levels and histopathology were less prominent.
      CONCLUSION: In this study, GD 20/21 rather than GD 19 appears to be the optimal
      time for investigating changes in anogenital distance, testosterone levels, and
      testicular histopathology. DiBP has similar testicular and developmental effects
      as DBP and DEHP, and although more developmental and especially postnatal studies
      are needed to clearly identify the reproductive effects of DiBP, this study
      indicates a reason for concern about the use of DiBP as a substitute for DBP.

PMID- 16458460
TI  - The time course of recovery from suppression and facilitation from single units
      in the mammalian cochlear nucleus.
AB  - The responses to two identical, consecutive pure tone stimuli with varying inter
      stimulus intervals (delta ts) were measured for 89 neurons in the cochlear
      nucleus of the anaesthetised guinea pig. We observed two main effects; either a
      decrease (suppression) or an increase (facilitation) in response to the second
      tone followed by an exponential recovery. Response behaviour correlated with the
      unit type; primary-like, primary-like with notch and transient-chopper units
      showed a recovery from suppression that was very similar to that already reported
      in the auditory nerve. For chopper units the strength of the adaptation was
      correlated with the units regularity of spike discharge; sustained chopper (CS)
      units showed less suppression than transient choppers. Onset units showed
      complete suppression at short delta ts. Pause/Build (PB) units responded with
      increased activity to the second tone. In contrast to previous studies in the
      cochlear nucleus the recovery from suppression or facilitation was well described
      by a single exponential function, enabling us to define a recovery time constant
      and a maximum suppression/facilitation. There appeared to be a hierarchy in the
      time constant of recovery with PB and CS units showing the longest recovery times
      and onset units showing the shortest.

PMID- 16458461
TI  - Bioactive sesquiterpene lactones from the leaves of Vernonia amygdalina.
AB  - Phytochemical analysis of the leaves of Vernonia amygdalina yielded two known
      sesquiterpene lactones: vernolide and vernodalol. The two compounds were tested
      by agar dilution method against 10 bacteria strains and 5 fungi species. Both
      compounds exhibited a significant bactericidal activity against five Gram
      positive bacteria while lacking efficacy against the Gram negative strains. In
      the antifungal test, while vernolides exhibited high activity with LC(50) values
      of 0.2, 0.3 and 0.4 mg/ml against Penicillium notatum, Aspergillus flavus,
      Aspergillus niger and Mucor hiemalis, respectively, vernodalol showed moderate
      inhibitions against Aspergillus flavus, Penicillium notatum and Aspergillus niger
      with LC(50) values of 0.3, 0.4 and 0.5 mg/ml, respectively. Both compounds were
      ineffective against Fusarium oxysporum, a microbe known to be highly resistant to
      chemical agents. However, the antimicrobial results of this study correspond
      positively with the claimed ethnomedical uses of the leaves of Vernonia
      amygdalina in the treatment of various infectious diseases.

PMID- 16458462
TI  - Paeonol reduced cerebral infarction involving the superoxide anion and microglia
      activation in ischemia-reperfusion injured rats.
AB  - Both Moutan cortex of Paeonia suffruticosa Andrews (MC) and the root of Paeonia
      lactiflora Pall (PL) are important Traditional Chinese herbs used commonly to
      treat inflammatory and pyretic disorders. Paeonol, a common component of MC
      causes anti-platelet aggregation and scavenges free radicals. Therefore, the aim
      of the present study is to investigate the effects of Paeonol on cerebral
      infarct. A total of 60 male Sprague-Dawley (SD) rats were studied. An animal
      model of cerebral infarct was established by occluding both common carotid
      arteries and the right middle cerebral artery for 90 min, followed by a 24 h
      period of reperfusion. The percentage of cerebral infarction area to total brain
      area in each piece of brain tissue, and neuro-deficit score were measured.
      Superoxide anion was determined by the number of lucigenin-chemiluminescence (CL)
      counts. ED1 (mouse anti rat CD68) and interleukin-1beta (IL-1beta) immunostaining
      in the cerebral infarction region were also investigated for activation of
      microglia. The results indicated that Paeonol 15 and 20 mg/kg pretreatment and 20
      mg posttreatment reduced the cerebral infarction area; Paeonol 15 and 20 mg/kg
      pretreatment reduced the neuro-deficit score. In addition, Paeonol 20 mg/kg
      pretreatment reduced the lucigenin-CL counts at 2 h period of reperfusion. The
      number of ED1 and IL-1beta immunoreactive cells also reduced in the cerebral
      infarction region; there were no significant changes in blood sugar levels. The
      results show that Paeonol reduced cerebral infarct and neuro-deficit in rat,
      suggesting Paeonol might play a similar role in reducing cerebral infarction in
      humans. Paeonol suppresses and scavenges superoxide anion, and inhibit microglia
      activation and IL-1beta in ischemia-reperfusion injured rats.

PMID- 16458463
TI  - Medicinal plants used by Tanzanian traditional healers in the management of
      Candida infections.
AB  - An ethnomedical survey in Coast, Dar es Salaam, Morogoro and Tanga regions of
      Tanzania has resulted in the identification of 36 plant species belonging to 21
      plant families that are used traditionally for the treatment of Candida
      infections. Twenty-one plants constituting 58.3% of all collected plants are used
      to treat of oral candidiasis (Utando) one of the important signs of HIV/AIDS. The
      knowledge of traditional healers for the treatment of Candida infections has been
      highly supported by the literature in that 13 (36.1%) out of the 36 plants
      identified have been proven to be active against Candida albicans and/or other
      species of Candida. Also, some of the plants were reported to be active against
      other species of fungi including Cryptococcus neoformans, one of the important
      pathogenic fungi in HIV/AIDS. It can be seen that ethnomedical information from
      traditional healers provides a solid lead towards development of new drugs than
      random screening. The task that remains is to screen extracts prepared from these
      plants and perform a bioassay-guided fractionation of the active extracts so as
      to isolate the active compounds from these plants.

PMID- 16458464
TI  - [Pulmonary zygomycosis in a patient treated for invasive aspergillosis].
AB  - We report a pulmonary mucormycosis due to Absidia corymbifera. It occurred in a
      leukemic patient treated for a probable aspergillosis regressing after
      voriconazole treatment. The patient responded to surgery and a combination of
      liposomal amphotericin B and itraconazole. He was alive and well after 7-months
      of follow up.

PMID- 16458465
TI  - [Retroperitoneal emphysematous abscess].
AB  - The authors report a case of emphysematous psoas abscess. The patient, a 55 year
      old man, was insulinorequerant diabetic. He presented with abdominal pain and
      diabetic ketoacidosis. The diagnosis was made by CT-scan. No portal of entry was
      found. The evolution was fatal before surgery in spite of probabilistic
      antibiotherapy.

PMID- 16458466
TI  - [Bacteriologic profile of bacteremia due to multi-drug resistant bacteria at
      Charles-Nicolle Hospital of Tunis].
AB  - OBJECTIVE: The authors had for aim to evaluate the place of multi-drug resistant
      bacteria (MDR) in nosocomial bacteremia. MATERIALS AND METHODS: A retrospective
      study was carried out at the Microbiology laboratory of Charles Nicolle hospital
      of Tunis (2001-2003). One hundred and ninety-five isolated MDR [third generation
      cephalosporin resistant enterobacteria, methicillin-resistant Staphylococcus
      aureus (MRSA), Acinetobacter baumannii and Pseudomonas aeruginosa resistant to
      ceftazidime and imipenem]. An automated system was used to detect bloodstream
      infections. Microorganism identification was performed by conventional methods
      and antibiotic susceptibilities were determined by the disk diffusion method.
      RESULTS: MDR bacteria were resistant to third generation cephalosporins (29%), A.
      baumannii (24%), P. aeruginosa (24%), and MRSA (10%). ERC3G were resistant to
      aminosides and fluorquinolones. A. baumannii and P. aeruginosa had high
      resistance rates. Associated resistance rates in MRSA were moderate. CONCLUSION:
      MDR bacteria are of great concern in our hospital. This situation emphasizes the
      importance to maintain rigorous measures of hygiene as well as adapted antibiotic
      prescriptions.

PMID- 16458467
TI  - Proatherogenic pathways leading to vascular calcification.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in the
      western world and atherosclerosis is the major common underlying disease. The
      pathogenesis of atherosclerosis involves local vascular injury, inflammation and
      oxidative stress as well as vascular calcification. Vascular calcification has
      long been regarded as a degenerative process leading to mineral deposition in the
      vascular wall characteristic for late stages of atherosclerosis. However, recent
      studies identified vascular calcification in early stages of atherosclerosis and
      its occurrence has been linked to clinical events in patients with cardiovascular
      disease. Its degree correlates with local vascular inflammation and with the
      overall impact and the progression of atherosclerosis. Over the last decade,
      diverse and highly regulated molecular signaling cascades controlling vascular
      calcification have been described. Local and circulating molecules such as
      osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as
      critical regulators of vascular calcification. We here review the current
      knowledge on molecular pathways of vascular calcification and their relevance for
      the progression of cardiovascular disease.

PMID- 16458468
TI  - Evaluation of recA gene as a phylogenetic marker in the classification of dairy
      propionibacteria.
AB  - The aim of this study was to investigate the validity of recA gene as a molecular
      marker for the reliable discrimination and classification of dairy
      propionibacteria and the closely related species. Regions of the recA gene,
      varying in size between 613 and 677 nucleotides, were sequenced for
      Propionibacterium acidipropionici, P. cyclohexanicum, P. freudenreichii, P.
      jensenii, P. microaerophilum and P. thoenii using degenerate consensus primers
      constructed by aligning recA sequences of some actinobacteria. The 16S rRNA
      encoding genes for the type and reference strains of the species P.
      acidipropionici, P. jensenii and P. thoenii were also sequenced to remove
      ambiguous positions present in the current database reports, such to improve the
      classification scheme of reference. As found for other bacterial species, recA
      sequences permitted a better distinction among the dairy propionibacteria
      considered than 16S rRNA gene. However, the topology of phylogenetic trees
      constructed on the recA gene regions sequenced and their putative translations
      appeared rather different and less statistically valid than the 16S rRNA gene
      tree. In addition, the possibility of designing PCR-based identification and
      detection tests on the new recA sequences was demonstrated by assessing specific
      amplification protocols for P. cyclohexanicum and P. microaerophilum.

PMID- 16458469
TI  - Phenotypic and genotypic characterization of some Moorella sp. strains isolated
      from canned foods.
AB  - Six anaerobic thermophilic strains isolated from various spoiled cans including
      fish soups and cooked meats were characterized using a polyphasic approach. These
      strains were closely related to Moorella thermoacetica or Moorella
      thermoautotrophica species. Except the spacer region between the 16S and the 23S
      rRNA genes, which exhibited two PCR profiles distinguishing both species, the
      genotypic and phylogenetic analyses grouped these isolates, the type strains, and
      all sequences of Moorella thermoacetica and Moorella thermoautotrophica species
      contained in the GenBank database within a unique cluster. Moreover, all 16S rDNA
      sequences shared two characteristic DNA fragments, which were highly specific of
      Moorella thermoacetica/Moorella thermoautotrophica strains. However, taken
      together, the phenotypic, physiological and genotypic methods were conflicting,
      and did not enable affiliation of the isolates with one or the other species. To
      our knowledge, this study represents the first report of characterization of
      Moorella species isolated from spoiled cans. These results and previous work,
      very strongly argue in favor of questioning the taxonomic status of the two
      species.

PMID- 16458470
TI  - A molecular approach to the characterization of the eukaryotic communities of an
      extreme acidic environment: methods for DNA extraction and denaturing gradient
      gel electrophoresis analysis.
AB  - The diversity of the phytobenthonic community present in six acidophilic
      microbial mats from Rio Tinto (Iberian Pyritic Belt, SW Spain) was analysed by
      optical microscopy and two molecular techniques, denaturing gradient gel
      electrophoresis (DGGE) and sequence analysis of 18S rDNA cloned gene fragments.
      Sixteen DNA isolation protocols as well as two commercial DNA extraction kits
      were tested and their efficiency compared. Purified DNA extracts were amplified
      by PCR using universal eukaryotic primers and the PCR products analysed by DGGE.
      Bead-mill homogenization was found to be superior to the other cell lysis
      methodologies assayed (sonication or freeze-thawing cycles) as it allowed
      efficiencies of cell disruption of over 95%. The methods combining bead-mill
      homogenization in the presence of SDS, treatment with chemical extractants
      (hexadecylmethylammonium bromide or guanidine isothiocyanate) and phenol
      extraction resulted in DNA preparations that amplified the same number of bands
      when analysed by DGGE as the two commercial kits assayed. The phylogenetic
      affiliations of the DGGE bands were determined by a BLAST search, and nine
      different species related to the Chlorophyta, Ciliophora, Kinetoplastida,
      Ascomycota, Streptophyta and Colcochaetales taxonomical groups were identified.
      Similar levels of diversity were found using cloning procedures. Although not all
      the species observed under the microscope were detected using molecular
      techniques, e.g. euglenas, heliozoan, or amoebae, DGGE fingerprints showed rather
      well the level of diversity present in the samples analysed, with limitations
      similar to cloning techniques.

PMID- 16458471
TI  - Flow injection chemiluminescent determination of amiodarone in pharmaceutical
      preparations using photogenerated tris(2,2'-bipyridyl)ruthenium(III).
AB  - A flow injection configuration was developed and evaluated for the
      chemiluminescent determination of amiodarone. The method is based on the reaction
      of the drug with tris(2,2'-bipyridyl)ruthenium(III), which was generated through
      the on-line photo-oxidation of tris(2,2'-bipyridyl)ruthenium(II) with
      peroxydisulfate. Under the optimum experimental conditions, a linear calibration
      graph was obtained over the range 3.0-60.0 microg ml(-1) with a detection limit
      of 0.28 microg ml(-1). The proposed method allows 120 injections h(-1) with
      excellent repeatability and precision (R.S.D. less than 0.5% and 2.8%,
      respectively) and a reagent consumption of only 0.37 micromol (0.27 mg) of
      Ru(bpy)(3)Cl(2) x 6H(2)O per determination. The method was successfully applied
      to the determination of amiodarone in commercial pharmaceutical formulations.

PMID- 16458472
TI  - Improved quality control method for Danshen products--consideration of both
      hydrophilic and lipophilic active components.
AB  - The current study intends to provide an improved quality control analysis for
      Danshen product-a representative herbal product with known active components that
      are both hydrophilic and lipophilic in nature. A simple HPLC method with
      photodiode-array (PDA) ultraviolet detection was developed for the simultaneous
      determination of three major lipophilic components (cryptotanshinone, tanshinone
      I and tanshinone IIA) and three major hydrophilic components (danshensu,
      protocatechuic aldehyde and salvianolic acid B) of Danshen (Salvia miltiorrhiza).
      These six components were successfully separated using Radial-pak C18 cartridge
      with the elution gradient consisting of 0.5% acetic acid in water and 0.5% acetic
      acid in acetonitrile at a flow rate of 1 ml/min. The intra-day and inter-day
      precisions of the analysis were within 2.32 and 2.0%, respectively. The detection
      limits were 0.02, 0.01, 0.01, 0.05, 0.005 and 0.02 microg/ml for
      cryptotanshinone, tanshinone I, tanshinone IIA, danshensu, protocatechuic
      aldehyde and salvianolic acid B, respectively. The developed method has been
      applied to the simultaneous determination of above six major components in Fufang
      Danshen Tablet and Dripping Pill products by extraction with methanol and water.
      It has been demonstrated that salvianolic acid B and danshensu are the major
      components among the eight commercial Fufang Danshen products studied. The
      current developed method with methanol as extraction solvent provides a simple
      and efficient method for simultaneous detection of both lipophilic and
      hydrophilic major components in Danshen products.

PMID- 16458473
TI  - Application of nuclear magnetic resonance spectroscopy for quantitative analysis
      of miconazole, metronidazole and sulfamethoxazole in pharmaceutical and urine
      samples.
AB  - Specific, accurate and precise NMR methods were developed for determining
      miconazole, metronidazole and sulfamethoxazole antibiotic drugs in authentic,
      pharmaceutical and urine samples. Proton nuclear magnetic resonance spectroscopy
      (1H NMR) with maleic acid as an internal standard and DMSO-d6 as NMR solvent were
      used. 1H NMR signals at 9.0, 8.06, 7.50 and 6.26 ppm corresponding to miconazole,
      metronidazole, sulfamethoxazole and maleic acid were respectively used for
      calculating the concentrations of drugs per unit dose. Average percent recoveries
      of (97.54-101.10), (98.06-100.46) and (97.83-102.83) with average uncertainties
      of 1.02, 0.45 and 0.86 were respectively obtained for determining authentic
      samples of miconazole, metronidazole and sulfamethoxazole in the concentration
      range of 0.92-170 mg/0.6 ml DMSO-d6. In pharmaceutical formulations and urine
      samples, average percent recoveries in the ranges of 97.50-101.33 and 94.46
      100.86 were respectively obtained. Relative standard deviations (R.S.D.)<or=2.68
      were obtained for analyzing the three drugs in authentic, pharmaceutical and
      urine samples. Admixtures of the three drugs in authentic, pharmaceutical and
      urine samples were analyzed. Good precisions (0.79-2.99%) and recoveries (93.40
      104.97%) were obtained indicating the high selectivity and resolving power of the
      developed NMR methods and no needs for separation steps. Applying statistical
      Student t-test revealed insignificant difference between the real and measured
      contents at the 95% confidence level. F-test revealed insignificant difference in
      precisions between the developed NMR methods and HPLC methods reported for
      analyzing miconazole, metronidazole and sulfamethoxazole.

PMID- 16458474
TI  - Development of a biosensor based on gilo peroxidase immobilized on chitosan
      chemically crosslinked with epichlorohydrin for determination of rutin.
AB  - A new reagentless biosensor for the square-wave voltammetric determination of
      rutin in pharmaceutical formulations was developed by immobilization of gilo
      (Solanum gilo) crude extract in chitosan matrix. The gilo tissue acts as a source
      of peroxidase. The highest biosensor performance was obtained after
      immobilization of the peroxidase in chemically crosslinked chitosan with
      epichlorohydrin and glutaraldehyde that was incorporated in a carbon paste
      electrode. In the presence of hydrogen peroxide this enzyme catalyses the
      oxidation of rutin to quinone and the electrochemical reduction of the product
      was obtained at a fixed potential of +124 mV versus Ag/AgCl (3.0 M KCl). The
      performance and factors influencing the resulting biosensor were studied in
      detail. The bioelectrode exhibited a linear response for rutin concentrations
      from 3.4x10(-7) to 7.2x10(-6) M (r=0.9998) and the recovery of rutin from the
      samples ranged from 96.2 to 102.4%. The detection and quantification limits were
      2.0x10(-8) and 6.3x10(-8) M, respectively. The relative standard deviation was
      less than 1.0% for solutions containing 3.4x10(-7) to 7.2x10(-6) M rutin in 0.1 M
      phosphate buffer solution at pH 7.0 (n=10). The lifetime of this biosensor was 8
      months (at least 500 determinations).

PMID- 16458475
TI  - Comparison of electrospray ionization mass spectrometry and evaporative light
      scattering detections for the determination of Poloxamer 188 in itraconazole
      injectable formulation.
AB  - A high performance liquid chromatography (HPLC) method for Poloxamer 188 using
      size-exclusion chromatography (SEC) was developed and two different detection
      mechanisms, evaporative light scattering (ELSD) and electrospray ionization mass
      spectrometry (ESI-MS), were compared for their quantification capabilities in
      itraconazole formulation. Both detection techniques coupled with SEC separation
      were highly effective for the determination of Poloxamer 188, which is difficult
      to analyze by other common HPLC methods. As expected, ESI-MS detection provided
      sensitivity and selectivity superior to ELSD. But since the analyte is an
      excipient in the formulation, high sensitivity was not required and ELSD's
      simplicity and ruggedness made it more appropriate for routine analysis of this
      formulation.

PMID- 16458476
TI  - Evaluation of the CombiChip Mycobacteria Drug-Resistance detection DNA chip for
      identifying mutations associated with resistance to isoniazid and rifampin in
      Mycobacterium tuberculosis.
AB  - The CombiChip Mycobacteriatrade mark Drug-Resistance Detection DNA chip, recently
      developed by GeneIn (Pusan, South Korea), is an oligonucleotide microchip coupled
      with polymerase chain reaction for the detection of mutations associated with
      resistance to isoniazid (INH) and rifampin (RIF). This oligonucleotide chip was
      compared with DNA sequencing and phenotypic drug susceptibility testing with 69
      INH- and/or RIF-resistant and 27 all tested drug-susceptible Mycobacterium
      tuberculosis isolates. Two selected codons (the katG codon 315 and inhA15)
      allowed identification of 84.1% of INH-resistant isolates and 100% of RIF
      resistance were detected by screening for 7 codons: rpoB511, rpoB513, rpoB516,
      rpoB522, rpoB526, rpoB531, and rpoB533. The overall specificity of this
      oligonucleotide chip for detecting INH and RIF resistance were 100 and 95.3%,
      respectively. This level of sensitivity and specificity is concordant with that
      from the determination of M. tuberculosis drug resistance by DNA sequencing. This
      oligonucleotide chip is a rapid and reliable genotypic method capable of
      detecting multiple mutations associated with INH and RIF resistance
      simultaneously in a single microchip slide.

PMID- 16458477
TI  - [Preoperative cardiac assessment using dobutamine stress echocardiography].
AB  - Postoperative myocardial ischaemia is the leading cause of life expectancy
      impairment after high cardiac risk surgical procedures. Preoperative
      identification of patients at high risk for such complication helps reducing its
      postoperative incidence through therapeutic adjustments. The former relies upon
      preoperative selection of patients who are candidates for cardiac testing using
      dobutamine stress echocardiography, according to ACC/AHA guidelines. This exam
      evaluates echographic myocardial response to a pharmacological stress induced by
      dobutamine infusion. Its aim is to reproduce part of the stress the myocardium
      will undergo during surgical procedure. A stress induced myocardial ischaemia
      suggests such a complication could occur postoperatively. A positive dobutamine
      stress echocardiography justifies to prescribe preoperative anti-ischaemic
      treatment in order to reduce the cardiac risk of the further surgical procedure.
      Moreover, it justifies clear definition of perioperative haemodynamic objectives.
      Whatever the result of the dobutamine stress echocardiography, cardiac ischaemia
      should be monitored up to the third postoperative day on the basis of a daily 12
      lead electrocardiogram recording and daily plasmatic troponin Ic measurement.

PMID- 16458478
TI  - The complexity of antisense transcription revealed by the study of developing
      male germ cells.
AB  - Computational analyses have identified the widespread occurrence of antisense
      transcripts in the human and the mouse genome. However, the structure and the
      origin of the majority of the antisense transcripts are unknown. The presence of
      antisense transcripts for 19 of 64 differentially expressed genes during mouse
      spermatogenesis was demonstrated with orientation-specific RT-PCR. These
      antisense transcripts were derived from a wide variety of origins, including
      processed sense transcripts, intronic and exonic sequences of a single gene or
      multiple genes, intergenic sequences, and pseudogenes. They underwent normal and
      alternative splicing, 5' capping, and 3' polyadenylation, similar to the sense
      transcripts. There were also antisense transcripts that were not capped and/or
      polyadenylated. The testicular levels of the sense transcripts were higher than
      those of the antisense transcripts in all cases, while the relative expression in
      nontesticular tissues was variable. Thus antisense transcripts have complex
      origins and structures and the sense and antisense transcripts can be regulated
      independently.

PMID- 16458480
TI  - Perceptual identification and acoustic measures of the resonant voice based on
      "Lessac's Y-Buzz"--a preliminary study with actors.
AB  - This study aimed to verify whether the resonant voice based on Lessac's Y-Buzz
      can be perceived by listeners as resonant and different from habitual voice and
      to compare them to determine whether this sound exploration improves the vocal
      production. Nine newly graduated actors, six men and three women without voice
      complaints, were the subjects. They received a session of Lessac's Y-Buzz
      training from the primary investigator. Before training, they were asked to
      sustain the vowel /i/ at comfortable frequency and habitual loudness. After
      training, they were requested to sustain the Y-Buzz they had learned at a
      comfortable frequency and habitual loudness. Three speech-language pathologists
      (SLP) trained in voice developed an auditory-perceptive analysis. The pre- and
      posttraining voice samples were randomly spliced together, edited, and presented
      in pairs to perceptual judges who were asked to identify the most resonant of the
      pair. The voice samples were also acoustically compared through the Hoarseness
      Diagram and acoustic measures using the VoxMetria Software (CTS, version 2.0s,
      Brazil). The Y-Buzz trials were identified as resonant voice in 74% of the
      comparisons. The acoustic measures showed a statistically significant decrease of
      irregularity (P = 0.002) and shimmer (P = 0.38). The Hoarseness Diagram
      demonstrated how the resonant voice moved toward the normality for irregularity
      and noise components. The results showed that the resonant voice based on the Y
      Buzz can be identified as resonant and different from normal voicing in the same
      subject, and it apparently implies a better vocal production demonstrating a
      significant decrease of shimmer and irregularity through the Hoarseness Diagram
      evaluation.

PMID- 16458479
TI  - Consequences of paternal cocaine exposure in mice.
AB  - The present study examined the potential neuroteratological effects of paternal
      cocaine (COC) exposure using the novel mouse model of inhalational drug
      administration. In this model, mice were trained to self-administer COC in multi
      hour daily inhalation sessions reminiscent of crack binges. The controls included
      males pair-fed with COC-inhaling animals as well as ad-lib-fed males. All males
      were bred with drug-naive females. The newborn pups sired by COC-inhaling males
      had a reduced biparietal head diameter, suggesting a decreased cerebral volume.
      When the pups reached adulthood, their sustained visuo-spatial attention and
      spatial working memory were tested using a 5-arm maze paradigm. During the
      attention tests, the percentage of correct trials at the shortest stimulus
      duration employed in the study (0.5 s) was significantly lower for the male
      offspring of COC-inhaling fathers as compared to the offspring of both pair-fed
      and ad-lib-fed controls. For the females sired by COC-inhaling fathers, the
      deficit was observed at light stimulus durations of 0.5 and 0.75 s. Also, during
      the working memory tests, the male offspring of COC-inhaling fathers required
      more sessions than the offspring of either pair-fed or ad-lib-fed fathers to
      reach the selected criterion at retention intervals of 16 min and longer. The
      impairment of working memory in female offspring of COC-inhaling fathers was even
      stronger, as the offspring needed more sessions to reach the criterion as
      compared to their control counterparts, even at retention intervals as short as 4
      min. These findings suggest that paternal COC abuse prior to coitus may impact
      the development of the offspring, particularly if they are females. We further
      showed that chronic COC exposure in male mice does not result in substantial
      breakage of spermatozoal DNA, but significantly alters expression of DNA
      methyltransferases 1 and 3a in the germ cell-rich seminiferous tubules of the
      testis. Since these enzymes are essential for generating and maintaining parental
      gene imprinting in germ cells, our observations point to an intriguing
      possibility that COC may cause paternally induced neuroteratological effects by
      interfering with gene-imprinting patterns in male gametes.

PMID- 16458481
TI  - Plasma C-reactive protein concentration is not affected by isocaloric dietary fat
      reduction.
AB  - OBJECTIVE: There is a strong correlation between plasma C-reactive protein (CRP)
      concentration and risk of cardiovascular death. Low-fat diets have been
      recommended for maintenance of cardiovascular health, and it is known that a low
      fat diet associated with weight loss lowers CRP concentration. However, it
      remains unclear whether dietary fat has an effect independent from weight change
      on markers of inflammation. METHODS: Sixteen overweight subjects who were 46 +/-
      14 y old were placed on a weight-maintaining baseline diet consisting of 35% fat,
      45% carbohydrate, and 20% energy as protein. After 2 wk, subjects were switched
      to an isocaloric low-fat diet consisting of 15% fat, 65% carbohydrate, and 20%
      protein for another 2 wk. For the final 12 wk of the study, subjects consumed the
      same 15% fat diet ad libitum. At the end of each diet phase, CRP was measured by
      a high-sensitivity CRP assay. RESULTS: The weight of subjects remained stable
      during the first 4 wk of isocaloric diets. Plasma CRP concentrations after 2 wk
      on the weight-maintaining 35% fat diet and 2 wk on the isocaloric 15% fat diet
      were not significantly different (median +/- interquartile range 1.42 +/- 3.30
      and 1.59 +/- 3.29 mg/L, respectively). Three months of ad libitum low-fat diet
      consumption resulted in a 4.1 +/- 0.7 kg weight loss associated with a decrease
      in CRP concentration to 1.17 +/- 2.03 mg/L (P = 0.03). CONCLUSION: Loss of body
      weight decreases CRP concentration, but a decrease in dietary fat without a
      concurrent change in body weight does not affect CRP concentration in overweight
      healthy subjects.

PMID- 16458482
TI  - Dietary glutamine supplementation reduces cellular adhesion molecule expression
      and tissue myeloperoxidase activity in mice with gut-derived sepsis.
AB  - OBJECTIVES: This study investigated the effects of glutamine (Gln) on plasma
      intracellular adhesion molecule-1 levels and leukocyte integrin (CD11a/CD18 and
      CD11b/CD18) expressions in gut-derived sepsis. Myeloperoxidase (MPO) activities
      in organs were also analyzed to identify the extent of tissue injury resulting
      from neutrophil infiltration. METHODS: Mice were randomly assigned to a normal
      group (NC), a control group, or a Gln group. The NC group was fed standard chow
      diet; the control group was fed a common semipurified diet; and the Gln group
      received a diet in which part of the casein was replaced by Gln, which provided
      25% of total amino acid nitrogen. After 3 wk, sepsis was induced by cecal
      ligation and puncture (CLP) in the control and Gln groups. Mice in the
      experimental groups were killed at 0, 6, 12, and 24 h after CLP. Mice in the NC
      group were killed when CLP was performed. Blood and organ samples were collected
      for further analysis. RESULTS: Plasma intracellular adhesion molecule-1 levels
      were significantly lower in the Gln group than in the control group at 6, 12, and
      24 h after CLP. Expressions of lymphocyte CD11a/CD18 were significantly higher,
      whereas polymorphonuclear lymphocyte expressions of CD11b/CD18 were lower in the
      Gln group than in the corresponding control group at 6 and 12 h after CLP. In
      comparisons of MPO activities in various organs, the Gln group had lower MPO
      activities at 6 and 12 h in the lung, at 6, 12, and 24 h in the liver, at 12 and
      24 h in the kidneys, and at 12 h in the intestine than those in the control
      group. CONCLUSIONS: Results of this study demonstrate that a Gln-supplemented
      enteral diet increased lymphocyte CD11a/CD18 expressions, whereas neutrophil
      CD11b/CD18 expressions, circulating intracellular adhesion molecule-1 levels, and
      MPO activities in various organs decreased with gut-derived sepsis. These
      findings suggest that, under septic conditions, Gln administration may enhance
      lymphocyte function, attenuate interactions between polymorphonuclear lymphocytes
      and endothelium, and thus may decrease neutrophil infiltration into tissues.

PMID- 16458484
TI  - Effect of soy protein/animal protein ratio on calcium metabolism of the rat.
AB  - OBJECTIVE: This study examined the effects of a ratio of soy protein to animal
      protein on bone metabolism of rats. METHODS: Experimental groups were a high soy
      protein group (200 g of soy protein and 0 g of casein per kilogram of diet;
      HSoy), a middle soy protein group (100 g of soy protein and 100 g of casein per
      kilogram of diet; MSoy), a low soy protein group (50 g of soy protein and 150 g
      of casein per kilogram of diet; LSoy), and a no soy protein group (0 g of soy
      protein and 200 g of casein per kilogram of diet; NSoy). Calcium excretion and
      retention, biochemical parametrically related calcium metabolism, and bone
      mineral density were measured. Statistical analysis was performed with SAS
      software. RESULTS: Urinary excretion of calcium was significantly high in the
      LSoy and NSoy groups, and there was no difference in absorption of calcium across
      experimental groups. Calcium retention was significantly higher in the HSoy and
      MSoy groups than in the LSoy and NSoy groups. Experimental groups showed no
      differences in the activity of alkaline phosphatase. The casein group (NSoy)
      showed a remarkably lower degree of serum osteocalcin concentration. The
      concentration of deoxypyridinoline in urine showed an increasing tendency, i.e.,
      HSoy and MSoy < LSoy < NSoy, indicating that at a higher degree of animal
      protein/soy proteins, its concentration increases. Wet weight of the femur
      appeared to be significantly greater in the MSoy and LSoy groups than in the NSoy
      group. Ash content of the femur and bone density were highest in the MSoy group,
      with the ratio of 1:1 between soy protein and animal protein. CONCLUSIONS: This
      study indicated that deoxypyridinoline concentration was lower and the density of
      osteocalcin was higher in the MSoy group than in the NSoy group, and that calcium
      retention was high and bone mineral density was the highest in the MSoy group.
      The ratio of soy to animal protein that seemed to have the most positively
      significant effect on calcium metabolism was 1:1.

PMID- 16458483
TI  - Effects of conjugated linoleic acid on skeletal muscle triacylglycerol metabolism
      in hamsters.
AB  - OBJECTIVE: The present work evaluated the effects of conjugated linoleic acid
      (CLA) on various aspects of triacylglycerol metabolism in skeletal muscle to
      determine the potential involvement of this tissue in the effect of CLA to
      decrease body fat. METHODS: Animals were randomized to three groups that were fed
      atherogenic diets that provided different amounts of trans-10,cis-12 CLA (0%,
      0.5%, or 1%) for 6 wk. Muscle triacylglycerol, protein, water, glycogen, and DNA
      contents and fatty acid profile in triacylglycerols were analyzed. Lipoprotein
      lipase and carnitine palmitoyltransferase-I (CPT-I) activities were assessed.
      Triacylglycerol, glucose, and insulin concentrations were evaluated in serum.
      RESULTS: The high dose of CLA increased food efficiency and gastrocnemius muscle
      weight. CLA feeding resulted in decreased muscle triacylglycerol content without
      changes in protein, water, glycogen, and DNA contents or in cell size
      (protein/DNA ratio) and produced decreased lipoprotein lipase activity and
      increased CPT-I activity. No differences were found between CLA doses. CLA
      feeding led to the saturation of stored triacylglycerols. CONCLUSIONS: Decreased
      fatty acid uptake and increased fatty acid oxidation can contribute to the
      decreased muscle triacylglycerol content observed in hamsters fed the CLA diets.
      The increase in muscle fatty acid beta-oxidation might ultimately prevent storage
      of triacylglycerols in adipose tissue. Nevertheless, the lack of matching of
      lipoprotein lipase and CPT-I modifications makes it difficult to ensure that
      skeletal muscle is responsible, at least in part, for the effect of CLA on
      decreasing body fat; thus, further research is needed.

PMID- 16458485
TI  - Options available for the infusion of lipid emulsion in home parenteral nutrition
      (HPN): a questionnaire survey for hospitals in Japan where HPN is practiced.
AB  - OBJECTIVE: To understand the status of total parenteral nutritional (TPN)
      composition and the TPN line used for home parenteral nutrition (HPN) in Japan
      and to investigate how adequate nutritional support should be in HPN, we
      conducted a questionnaire survey. METHODS: From February to March 2004,
      questionnaires were sent by mail to the members of the Japan Society for Home
      Therapy Research. With the content of the questionnaire, we surveyed 1) the types
      of medical staff who are involved in HPN, 2) the status of the preparation of TPN
      fluid and its place of preparation, 3) use of the TPN line and final filter, and
      4) administration of lipid emulsion and All-in-One. RESULTS: The major survey
      results from 66 respondents were that the 50% of the medical staff who are
      involved in HPN have more than 10 y of experience; however, the number of
      patients who used HPN and were treated by 78% of the medical staff was fewer than
      50. With regard to TPN fluid, 50% was prepared in-house and 12% was prepared by
      home care service providers. In addition, 58% of institutions were infusing lipid
      emulsion from the side port of the TPN line or through a peripheral route because
      they used a final filter and closed system infusion line. CONCLUSIONS: Because
      the final filter and closed system infusion line for HPN management is standard
      practice, lipid emulsion is not adequately used in Japan. Therefore, the All-in
      One system including lipid emulsion is not used.

PMID- 16458486
TI  - Prevalence of subgingival bacteria resistant to aminopenicillins and
      metronidazole in dental patients from Yemen and Norway.
AB  - The purpose of this study was to assess the prevalence of resistance to
      aminopenicillins and metronidazole among selected subgingival species in dental
      patients from Yemen and Norway. Three subgingival samples were collected by paper
      points from each of 34 Yemeni and 21 Norwegian adult volunteers and then pooled.
      Each of the 55 pooled samples was plated on fastidious anaerobic blood agar
      containing 2 microg/mL ampicillin or metronidazole, or no antimicrobial. Species
      identification of growth was done using DNA-DNA checkerboard hybridisation. The
      overall proportion of ampicillin resistance among the 18 identified species was
      28.9% and 7.9% in the Yemeni and Norwegian samples, respectively, whereas for
      metronidazole it was 60.3% and 11.3%. The number of species resistant to
      ampicillin and metronidazole was significantly higher (P < 0.016 and P = 0.0000,
      respectively) in the Yemeni than in the Norwegian samples.

PMID- 16458487
TI  - Association study of two serotonin 1A receptor gene polymorphisms and fluoxetine
      treatment response in Chinese major depressive disorders.
AB  - The firing rate of dorsal raphe serotonergic neurons is modulated by
      somatodendritic 5-hydroxytryptamine 1A (HTR1A) autoreceptors. Evidence from
      animal and clinical studies has suggested that desensitization of HTR1A is
      implicated in the antidepressant therapeutic mechanism of selective serotonin
      reuptake inhibitors (SSRIs). Recent studies, including our recent findings, have
      reported that a functional HTR1A C-1019G polymorphism in the promoter region, as
      well as a nonsynonymous polymorphism, Gly272Asp, may be associated with SSRI
      pharmacogenetics. In this study, we tested whether Gly272Asp genetic variants are
      related to a 4-week fluoxetine antidepressant effect in 222 Chinese major
      depressive patients. We also tested the linkage disequilibrium (LD) measurement
      between HTR1A Gly272Asp and C-1019G polymorphisms, and haplotype analysis was
      conducted to assess the association between the two markers within the HTR1A gene
      and fluoxetine antidepressant response. The results show that the HTR1A Gly272Asp
      polymorphism was not associated with fluoxetine therapeutic response. The two
      markers are in strong LD and the HTR1A haplotype of the two polymorphisms is
      associated with fluoxetine therapeutic response. This association is gender
      specific and mostly arises from the effect of HTR1A C-1019G polymorphism: female
      patients with -1019C/C genotype showed a better response than -1019G carriers.
      These findings need to be confirmed in other ethnic populations.

PMID- 16458488
TI  - A genetic model for muscle-eye-brain disease in mice lacking protein O-mannose
      1,2-N-acetylglucosaminyltransferase (POMGnT1).
AB  - Protein O-mannose beta1,2-N-acetyglucosaminyltransferase 1 (POMGnT1) is an enzyme
      involved in the synthesis of O-mannosyl glycans. Mutations of POMGnT1 in humans
      result in the muscle-eye-brain (MEB) disease. In this study, we have
      characterized a null mutation generated by gene trapping with a retroviral vector
      inserted into the second exon of the mouse POMGnT1 locus. Expression of POMGnT1
      mRNA was abolished in mutant mice. Glycosylation of alpha-dystroglycan was also
      reduced. POMGnT1 mutant mice were viable with multiple developmental defects in
      muscle, eye, and brain, similar to the phenotypes observed in human MEB disease.
      The present study provides the first genetic animal model to further dissect the
      roles of POMGnT1 in MEB disease.

PMID- 16458489
TI  - Effects of oxymatrine on proliferation and apoptosis in human hepatoma cells.
AB  - Oxymatrine, a natural quinolizidine alkaloid, has been known having cytotoxic and
      chemopreventive effects on various cancer cells. To investigate the possible
      mechanism of oxymatrine's role on cancer cells, in the present study, we examined
      further the effects of oxymatrine on the growth, proliferation, apoptosis and
      expression of bcl-2 and p53 gene in human hepatoma SMMC-7721 cells in vitro. Our
      results show that oxymatrine notably inhibits the growth and proliferation of
      SMMC-7721 cells and it present a dose-dependence and time-dependence manner
      within definite reacting dose and time. Oxymatrine block SMMC-7721 cells in G2/M
      and S phase; prevent cells entering into G0/G1 phase. It results in an obvious
      accumulation of G2/M and S phase cells while decrease of G0/G1 phase cells.
      Oxymatrine induce apoptosis of SMMC-7721 cells and apoptotic rate amount to about
      60% after treatment with 1.0 mg/ml oxymatrine for 48 h. We also find that
      oxymatrine down-regulate expression of bcl-2 gene while up-regulate expression of
      p53 gene. These results demonstrate that oxymatrine inhibit the proliferation and
      induce apoptosis of human hepatoma SMMC-7721 cells, and suggest that this effect
      was mediated probably by a significant cell cycle blockage in G2/M and S phase,
      down-regulation of bcl-2 and up-regulation of p53.

PMID- 16458490
TI  - Light-regulated translocation of signaling proteins in Drosophila photoreceptors.
AB  - Illumination of Drosophila photoreceptor cells induces multi-facet responses,
      which include generation of the photoreceptor potential, screening pigment
      migration and translocation of signaling proteins which is the focus of recent
      extensive research. Translocation of three signaling molecules is covered in this
      review: (1) Light-dependent translocation of arrestin from the cytosol to the
      signaling membrane, the rhabdomere, determines the lifetime of activated
      rhodopsin. Arrestin translocates in PIP3 and NINAC myosin III dependent manner,
      and specific mutations which disrupt the interaction between arrestin and PIP3 or
      NINAC also impair the light-dependent translocation of arrestin and the
      termination of the response to light. (2) Activation of Drosophila visual G
      protein, DGq, causes a massive and reversible, translocation of the alpha subunit
      from the signaling membrane to the cytosol, accompanied by activity-dependent
      architectural changes. Analysis of the translocation and the recovery kinetics of
      DGq(alpha) in wild-type flies and specific visual mutants indicated that
      DGq(alpha) is necessary but not sufficient for the architectural changes. (3) The
      TRP-like (TRPL) but not TRP channels translocate in a light-dependent manner
      between the rhabdomere and the cell body. As a physiological consequence of this
      light-dependent modulation of the TRP/TRPL ratio, the photoreceptors of dark
      adapted flies operate at a wider dynamic range, which allows the photoreceptors
      enriched with TRPL to function better in darkness and dim background
      illumination. Altogether, signal-dependent movement of signaling proteins plays a
      major role in the maintenance and function of photoreceptor cells.

PMID- 16458491
TI  - Pharmacological and molecular enhancement of learning in aging and Alzheimer's
      disease.
AB  - When animals learn hippocampus-dependent associative and spatial tasks such as
      trace eyeblink conditioning and the water maze, CA1 hippocampal neurons become
      more excitable as a result of reductions in the post-burst, slow
      afterhyperpolarization. The calcium-activated potassium current that mediates
      this afterhyperpolarization is activated by the calcium influx that occurs when a
      series of action potentials fire and serves as a modulator of neuronal firing
      frequency. As a result, spike frequency accommodation is also reduced after
      learning. Neuronal calcium buffering processes change and/or voltage-dependent
      calcium currents increase during aging; leading to enhancements in the slow
      afterhyperpolarization, increased spike frequency accommodation and age
      associated impairments in learning. We describe a series of studies done to
      characterize this learning-specific enhancement in intrinsic neuronal
      excitability and its converse in aging brain. We have also combined behavioral
      pharmacology and biophysics in experiments demonstrating that compounds that
      increase neuronal excitability in CA1 pyramidal neurons also enhance learning
      rate of hippocampus-dependent tasks, especially in aging animals. The studies
      reviewed here include those using nimodipine, an L-type calcium current blocker
      that tends to cross the blood-brain barrier; metrifonate, a cholinesterase
      inhibitor; CI1017, a muscarinic cholinergic agonist; and galantamine, a combined
      cholinesterase inhibitor and nicotinic agonist. Since aging is the chief risk
      factor for Alzheimer's disease, a disease that targets the hippocampus and
      associated brain regions and markedly impairs hippocampus-dependent learning,
      these compounds have potential use as treatments for this disease. Galantamine
      has been approved by the USDA for this purpose. Finally, we have extended our
      studies to the TG2576 transgenic mouse model of Alzheimer's disease (AD), that
      overproduces amyloid precursor protein (APP) and increases levels of toxic beta
      amyloid in the brain. Not only do these mice show deficits in hippocampus
      dependent learning as they age, but their hippocampal neurons show a reduced
      capacity to increase their levels of intrinsic excitability with reductions in
      the slow afterhyperpolarization after application of the muscarinic agonist
      carbachol. These TG2576 APP overproducing mice were crossed with BACE1 knockout
      mice, that do not produce beta-amyloid because cleavage of APP by the beta-site
      APP cleaving enzyme 1 (BACE1) is a critical step in its formation. Not only was
      hippocampus-dependent learning rescued in the bigenic TG2576-BACE1 mice, but the
      capacity of hippocampal neurons to show normal enhancements of intrinsic
      excitability was restored. The series of studies reviewed here support our
      hypothesis that enhancement in intrinsic excitability by reductions in calcium
      activated potassium currents in hippocampal neurons is an important cellular
      mechanism for hippocampus-dependent learning.

PMID- 16458492
TI  - Nicotine enhances intracellular nicotinic receptor maturation: a novel mechanism
      of neural plasticity?
AB  - Nicotine addiction, the primary cause of tobacco consumption, is mediated through
      nicotine binding to brain nicotinic acetylcholine receptor (nAChRs). Upon chronic
      exposure, nicotine elicits a cascade of events, starting with nAChR activation
      and desensitization, followed by a long term up-regulation that corresponds to an
      increase in the number of the high affinity nAChRs, a paradoxical process that
      occurs in the brain of smokers. Recent investigation of the maturation and
      trafficking of the major brain alpha4beta2 nAChR demonstrates that up-regulation
      is initiated in the endoplasmic reticulum soon after protein translation. The
      data thus far accumulated provide evidence that nicotine elicits up-regulation by
      promoting maturation of nAChR precursors that would otherwise be degraded. This
      "maturational enhancer" action of nicotine probably contributes to the long term
      effect of chronic nicotine, and suggests a novel mechanism of neuronal plasticity
      through an yet unknown endogenous substance which would modulate the receptor
      expression under physiological conditions.

PMID- 16458493
TI  - The Ca2+-releasing messenger NAADP, a new player in the nervous system.
AB  - Many physiological processes are controlled by a great diversity of Ca2+ signals.
      Within cell, Ca2+ signals depend upon Ca2+ entry and/or Ca2+ release from
      internal Ca2+ stores. The control of Ca2+-store mobilization is ensured by a
      family of messengers comprising inositol 1,4,5 trisphosphate, cyclic ADP-ribose
      and nicotinic acid adenine dinucleotide phosphate (NAADP). From recent works, new
      concepts have emerged where activation of the cells by outside stimuli, acting at
      the plasma membrane, results in the synthesis of multiple Ca2+-releasing
      messengers which may interact and shape complex Ca2+ signals in the cytosol as
      well as in the nucleus. This contribution will cover the most recent advances on
      NAADP signalling with some emphasis on neurons.

PMID- 16458494
TI  - [Phytoestrogens and soy foods in infants and children: caution is needed].

PMID- 16458495
TI  - Measuring seasonal variations of moisture in a landfill with the partitioning gas
      tracer test.
AB  - Seven pilot-scale partitioning gas tracer tests (PGTTs) were conducted to assess
      the accuracy and reproducibility of this method for measuring water in municipal
      solid waste landfills. Tests were conducted in the same location over a 12-month
      period, and measured moisture conditions ranged from possible dry waste to refuse
      with a moisture content of 24.7%. The final moisture content of 24.7% was in
      reasonable agreement with gravimetric measurements of excavated refuse, where the
      moisture content was 26.5+/-6.0 CI%. Laboratory tests were used to assess the
      utility of the PGTT for measuring water in small pores, water sorbed to solid
      surfaces, and the influence of dry waste on PGTTs. These experiments indicated
      that when refuse surfaces are not completely solvated with water, PGTTs may
      produce misleading results (negative estimates) of water saturation and moisture
      content.

PMID- 16458496
TI  - In situ ammonia removal in bioreactor landfill leachate.
AB  - Although bioreactor landfills have many advantages associated with them,
      challenges remain, including the persistence of NH(3)-N in the leachate. Because
      NH(3)-N is both persistent and toxic, it will likely influence when the landfill
      is biologically stable and when post-closure monitoring may end. An in situ
      nitrogen removal technique would be advantageous. Recent studies have shown the
      efficacy of such processes; however, they are lacking the data required to enable
      adequate implementation at field-scale bioreactor landfills. Research was
      conducted to evaluate the kinetics of in situ ammonia removal in both acclimated
      and unacclimated wastes to aid in developing guidance for field-scale
      implementation. Results demonstrate that in situ nitrification is feasible in an
      aerated solid waste environment and that the potential for simultaneous
      nitrification and denitrification (even under low biodegradable C:N conditions)
      in field-scale bioreactor landfills is significant due to the presence of both
      aerobic and anoxic areas. All rate data fit well to Monod kinetics, with specific
      rates of removal of 0.196 and 0.117 mgN/day-g dry waste and half-saturation
      constants of 59.6 and 147 mgN/L for acclimated and unacclimated wastes,
      respectively. Although specific rates of ammonia removal in the unacclimated
      waste are lower than in the acclimated waste, a relatively quick start-up of
      ammonia removal was observed in the unacclimated waste. Using the removal rate
      expressions developed will allow for estimation of the treatment times and
      volumes necessary to remove NH(3)-N from recirculated landfill leachate.

PMID- 16458497
TI  - Integration of a surface acoustic wave biosensor in a microfluidic polymer chip.
AB  - SAW devices based on horizontally polarized surface shear waves (HPSSW) enable
      label-free, sensitive and cost-effective detection of biomolecules in real time.
      It is known that small sampling volumes with low inner surface areas and minimal
      mechanical stress arising from sealing elements of miniaturized sampling chambers
      are important in this field. Here, we present a new approach to integrate SAW
      devices with sampling chamber. The sensor device is encapsulated within a polymer
      chip containing fluid channel and contact points for fluidic and electric
      connections. The chip volume is only 0.9 microl. The polymeric encapsulation was
      performed tailor-made by Rapid Micro Product Development 3Dimensional Chip-Size
      Packaging (RMPD 3D-CSP), a 3D photopolymerisation process. The polymer housing
      serves as tight and durable package for HPSSW biosensors and allows the use of
      the complete chips as disposables. Preliminary experiments with these
      microfluidic chips are shown to characterise the performance for their future
      applications as generic bioanalytical micro devices.

PMID- 16458498
TI  - Development of biosensors for cancer clinical testing.
AB  - Biosensors are devices that combine a biochemical recognition/binding element
      (ligand) with a signal conversion unit (transducer). Biosensors are already used
      for several clinical applications, for example for electrochemical measurement of
      blood glucose concentrations. Application of biosensors in cancer clinical
      testing has several potential advantages over other clinical analysis methods
      including increased assay speed and flexibility, capability for multi-target
      analyses, automation, reduced costs of diagnostic testing and a potential to
      bring molecular diagnostic assays to community health care systems and to
      underserved populations. They have the potential for facilitating Point of Care
      Testing (POCT), where state-of-the-art molecular analysis is carried out without
      requiring a state-of-the-art laboratory. However, not many biosensors have been
      developed for cancer-related testing. One major challenge in harnessing the
      potential of biosensors is that cancer is a very complex set of diseases. Tumors
      vary widely in etiology and pathogenesis. Oncologists rely heavily on
      histological characterization of tumors and a few biomarkers that have
      demonstrated clinical utility to aid in patient management decisions. New genomic
      and proteomic molecular tools are being used to profile tumors and produce
      "molecular signatures." These signatures include genetic and epigenetic
      signatures, changes in gene expression, protein profiles and post-translational
      modifications of proteins. These molecular signatures provide new opportunities
      for utilizing biosensors. Biosensors have enormous potential to deliver the
      promise of new molecular diagnostic strategies to patients. This article
      describes some of the basic elements of cancer biology and cancer biomarkers
      relevant for the development of biosensors for cancer clinical testing, along
      with the challenges in using this approach.

PMID- 16458499
TI  - Glutamate optical biosensor based on the immobilization of glutamate
      dehydrogenase in titanium dioxide sol-gel matrix.
AB  - A simple and novel titania sol-gel derived optical biosensor coupled with carboxy
      seminaphthorhodamine-1-dextran (SNARF-1-dextran) as the fluorescent dye was
      fabricated for the determination of glutamate in water and biological samples.
      The NADH-dependent glutamate dehydrogenase (GLDH) was trapped in titania sol-gel
      derived matrix prepared by vapor deposition method. In addition, scanning
      electron microscopy (SEM) and atomic force microscopy (AFM) were used to
      characterize the surface morphology of the spots. SEM and AFM images showed that
      the deposition of titania precursor at 27 degrees C for 6.5h was found to be
      suitable to form transparent titania sol-gel matrix to encapsulate GLDH and
      fluorescent probe. AFM images showed that the roughness of TiO(2) surface
      increased from 2.16 nm in the absence of GLDH and SNARF to 37.8 nm after the
      immobilization. The developed titania biosensor has good analytical performance
      with water samples. A dynamic range between 0.04 and 10mM with the detection
      limit of 5.5 microM were observed. The responses to glutamate in biological
      samples also showed good performances, and the dynamic range and detection limit
      were 0.02-10mM and 6.7 microM, respectively. High precision with relative
      standard deviations of 4.2 and 10.7% in water and biological samples,
      respectively, were also demonstrated. In addition, the biosensor showed a
      relatively high storage stability over more than 1 month. Results obtained in
      this study clearly demonstrate that this simple vapor deposition method can be
      successfully used to form transparent titania sol-gel film for the fabrication of
      glutamate biosensors that are suitable for optical detection of glutamate in
      water and biological samples.

PMID- 16458500
TI  - Correlations between c-myc gene copy-number and clinicopathological parameters of
      ovarian tumours.
AB  - The objective of this study was to investigate increases in c-myc gene copy
      number in ovarian tumours, and to analyze their correlations with
      clinicopathological parameters. Here we applied FISH on TMA (tissue microarrays)
      containing 507 ovarian tumour samples from different malignancy, histology, stage
      and grade. Overall, we found high frequency for c-myc copy-number increases
      (38.5%) in ovarian cancers: 22.1% amplifications and 16.4% gains. We established
      c-myc amplification in more than 30% in endometrioid and mixed epithelial ovarian
      carcinomas. c-myc gains were found in a high proportion (42.9%) of clear cell
      carcinomas. We found associations between c-myc copy-number changes and
      clinicopathological parameters of ovarian tumours such as degree of malignancy
      and histological type. We suggested that c-myc amplifications are characteristics
      for endometrioid, and c-myc gains for clear cell ovarian cancers. We suggest that
      copy-number increases of c-myc and 20q13.2 represent a possible mechanism for the
      regulation of the pathway STK15--c-myc--hTERT.

PMID- 16458501
TI  - Observations on the suppression of root-knot nematode (Meloidogyne arenaria) on
      tomato by incorporation of cyanobacterial powder (Oscillatoria chlorina) into
      potting field soil.
AB  - Experiments were carried out to investigate the nematicidal potential of a
      cyanobacterium, Oscillatoria chlorina, against the root-knot nematode,
      Meloidogyne arenaria on tomato plants grown in pots filled with 500 cm3 of field
      soil infested with 12-s stage juveniles (J2)/cm3 soil. Incorporation of freeze
      dried cyanobacterial powder into potted field soil at the rate of 0.2%, 0.4%,
      0.6%, 0.8% and 1.0% (w/w) 5 days prior to tomato planting, reduced root galling,
      final population of M. arenaria and increased vegetative growth of tomato plants
      and root-mass production, compared with untreated control (P > or = 0.05). The
      beneficial effect of adding cyanobacterial powder into infested potted field soil
      increased exponentially with concentration up to 0.8%. Root galling and nematode
      population decreased by 68.9% and 97.6%, respectively at the highest dose (1%) of
      cyanobacterial powder compared with the untreated control. Addition of
      cyanobacterial powder into infested potted field soil at 5 days before planting
      was the most effective followed by 2 days before and at the time of tomato
      planting. We conclude that application rate and timing are important factors in
      the control of root-knot nematodes with O. chlorina.

PMID- 16458502
TI  - Assessment of permeable covers for odour reduction in piggery effluent ponds. 1.
      Laboratory-scale trials.
AB  - A variety of materials were trialed as supported permeable covers using a series
      of laboratory-scale anaerobic digesters. Efficacy of cover performance was
      assessed in terms of impact on odour and greenhouse gas emission rate, and the
      characteristics of anaerobic liquor. Data were collected over a 12-month period.
      Initially the covers reduced the rate of odour emission 40-100 times relative to
      uncovered digesters. After about three months, this decreased to about a
      threefold reduction in odour emission rate, which was maintained over the
      remainder of the trial. The covers did not alter methane emission rates. Carbon
      dioxide emission rates varied according to cover type. Performance of the covers
      was attributed to the physical characteristics of the cover materials and changes
      in liquor composition. The reductions in odour emission indicate that these
      covers offer a cost-effective method for odour control.

PMID- 16458503
TI  - Design and synthesis of 7H-pyrrolo[2,3-d]pyrimidines as focal adhesion kinase
      inhibitors. Part 1.
AB  - A series of 2-amino-9-aryl-7H-pyrrolo[2,3-d]pyrimidines were designed and
      synthesized to target focal adhesion kinase (FAK). A number of these
      pyrrolopyrimides exhibited low micromolar inhibitory activities against focal
      adhesion kinase, and their preliminary SAR was established via systematic
      chemical modifications. The 2-amino-9-aryl-7H-pyrrolo[2,3-d]pyrimidines represent
      a new class of kinase inhibitors.

PMID- 16458504
TI  - Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-{4-[4-(3
      methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3,5-dione: a
      novel agonist 5-HT1A receptor PET ligand.
AB  - Synthesis and in vivo evaluation of 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]
      butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and
      selective serotonin 5-HT1AR agonist PET tracer, are described. GTPgammaS assay
      shows that MMT is an agonist with an EC50 comparable to 5-HT. Radiolabeling of 5
      was achieved in 30% yield (EOS) from desmethyl-MMT (4) with >99% chemical and
      radiochemical purities and a specific activity >1000 Ci/mmol. PET studies in
      baboon show that [11C]5 penetrates the blood-brain barrier but, because of low
      specific binding and fast clearance of radioactivity it is not a suitable PET
      tracer for the in vivo quantification of 5-HT1AR.

PMID- 16458505
TI  - Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery
      of GW0385.
AB  - A novel series of P1 modified HIV protease inhibitors was synthesized and
      evaluated for in vitro antiviral activity against wild-type virus and protease
      inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds
      with femtomolar enzyme activities and cellular antiviral activities in the low
      nanomolar range culminating in the identification of clinical candidate GW0385.

PMID- 16458506
TI  - Abacavir prodrugs: microwave-assisted synthesis and their evaluation of anti-HIV
      activities.
AB  - The synthesis of a new series of abacavir prodrugs involving N2-substitution with
      various substituted benzaldehyde and ketone derivatives is described. The in
      vitro anti-HIV activities indicated that compound (3-(2-(4
      methylaminobenzylideneamino)-6-(cyclopropylamino)-9H-purin-9
      yl)cyclopentyl)methanol (3) was found to be most potent compound with EC50 of
      0.05 microM and CC50 of >100 microM with selectivity index of >2000. Compound 3
      was found to be 32 times more potent than the parent drug (EC50 of 1.6 microM).
      At pH 7.4, 37 degrees C, the hydrolytic t1/2 ranged between 120 and 240 min.

PMID- 16458507
TI  - Factor VIIa inhibitors: a prodrug strategy to improve oral bioavailability.
AB  - We have developed a series of potent and selective factor VIIa inhibitors based
      on the 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]
      succinic acid scaffold. These amidine-containing compounds have low oral
      bioavailability. Herein, we describe our efforts to improve the oral
      bioavailability of the parent amidine via a prodrug strategy where the amidine
      basicity and polarity were reduced with either an alkoxy-amidine or a carbamate
      prodrug.

PMID- 16458508
TI  - Identification and structure-activity relationships of a new series of
      Melanocortin-4 receptor antagonists.
AB  - The identification and optimization of a series of acylguanidine-based
      melanocortin-4 receptor antagonists is discussed.

PMID- 16458509
TI  - Synthesis and anticancer activity of thiosemicarbazones.
AB  - Twenty-six thiosemicarbazones (III-1-III-26) were synthesized via three steps
      starting from hydrazine hydrate and carbon disulfide. The testing of anticancer
      activity of these compounds in vitro against P-388, A-549, and SGC-7901 shows
      that compounds III-15 and III-16 possess a higher inhibitory ability for P-388
      and SGC-7901. Further testing shows that the value of IC50 of compound III-16
      against SGC-7901 reaches to 0.032 microM.

PMID- 16458510
TI  - The SAR of 4-substituted (6,6-bicyclic) piperidine cathepsin S inhibitors.
AB  - A series of competitive, reversible cathepsin S (CatS) inhibitors was
      investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1
      benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4
      arylpiperazin-1-yl group found in our screening hit. Continued investigation into
      replacements for the 4-aryl piperazine resulted in the identification of
      potentially useful CatS inhibitors with enzymatic and cellular activity similar
      to that of JNJ 10329670 as disclosed in a previous publication.

PMID- 16458511
TI  - Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl
      tetrahydroisoquinoline lead series.
AB  - In a high-throughput screening effort, a series of tetrahydroisoquinolines was
      identified as modest inhibitors of human Eg5. A medicinal chemistry optimization
      effort led to the identification of R-4-(3-hydroxyphenyl)-N,N-7,8-tetramethyl-3,4
      dihydroisoquinoline-2(1H)-carboxamide (32a) as a potent inhibitor of human Eg5
      (ATPase IC50 104 nM) with good anti-proliferative activity in A2780 cells (IC50
      234 nM).

PMID- 16458512
TI  - Specific inhibitors of Plasmodium falciparum thioredoxin reductase as potential
      antimalarial agents.
AB  - Plasmodium falciparum thioredoxin reductase (PfTrxR: NADPH+Trx(S)2+H+<-
      >NADP++Trx(SH)2) is a high Mr flavin-dependent TrxR that reduces thioredoxin
      (Trx) via a CysXXXXCys pair located penultimately to the C-terminal Gly. In this
      respect, PfTrxR differs significantly from its human counterpart which bears a
      Cys-Sec redox pair at the same position. PfTrxR is essentially involved in
      antioxidant defense and redox regulation of the parasite and has been previously
      validated by knock-out studies as a potential drug target for malaria
      chemotherapy. Moreover, human TrxR is present in most cancer cells at levels
      tenfold higher than in normal cells. Here we report the discovery of a series of
      potent inhibitors of PfTrxR. The three most promising inhibitors,
      3(IC50(PfTrxR)=2 microM and IC50(hTrxR)=50 microM), 7(IC50(PfTrxR)=2 microM and
      IC50(hTrxR)=140 microM), and 11(IC50(PfTrxR)=0.5 microM and IC50(hTrxR)=4 microM)
      were selective for the parasite enzyme. Detailed mechanistic characterization of
      the effects of these compounds on the PfTrxR-catalyzed reaction showed clear
      uncompetitive inhibition with respect to both substrate and cofactor. For the
      most specific PfTrxR inhibitor 7, an alkylation mechanism study based on a thiol
      conjugation model was performed. Furthermore, all three compounds were active in
      the lower micromolar range on the chloroquine-resistant P. falciparum strain K1
      in vitro.

PMID- 16458513
TI  - Developmental control of nuclear size and shape by Kugelkern and Kurzkern.
AB  - BACKGROUND: The shape of a nucleus depends on the nuclear lamina, which is
      tightly associated with the inner nuclear membrane and on the interaction with
      the cytoskeleton. However, the mechanism connecting the differentiation state of
      a cell to the shape changes of its nucleus are not well understood. We
      investigated this question in early Drosophila embryos, where the nuclear shape
      changes from spherical to ellipsoidal together with a 2.5-fold increase in
      nuclear length during cellularization. RESULTS: We identified two genes,
      kugelkern and kurzkern, required for nuclear elongation. In kugelkern- and
      kurzkern-depleted embryos, the nuclei reach only half the length of the wild-type
      nuclei at the end of cellularization. The reduced nuclear size affects
      chromocenter formation as marked by Heterochromatin protein 1 and expression of a
      specific set of genes, including early zygotic genes. kugelkern contains a
      putative coiled-coil domain in the N-terminal half of the protein, a nuclear
      localization signal (NLS), and a C-terminal CxxM-motif. The carboxyterminal CxxM
      motif is required for the targeting of Kugelkern to the inner nuclear membrane,
      where it colocalizes with lamins. Depending on the farnesylation motif,
      expression of kugelkern in Drosophila embryos or Xenopus cells induces
      overproliferation of nuclear membrane. CONCLUSIONS: Kugelkern is so far the first
      nuclear protein, except for lamins, that contains a farnesylation site. Our
      findings suggest that Kugelkern is a rate-determining factor for nuclear size
      increase. We propose that association of farnesylated Kugelkern with the inner
      nuclear membrane induces expansion of nuclear surface area, allowing nuclear
      growth.

PMID- 16458515
TI  - Pseudoaneurysm of the medial inferior genicular artery following anterior
      cruciate ligament reconstruction with hamstring tendon autograft.
AB  - Vascular injuries associated with arthroscopic surgery of the knee are uncommon.
      Pseudoaneurysm of the medial inferior genicular artery after hamstring tendon ACL
      reconstruction has not been reported yet. Diagnosis can be obtained clinically if
      continuous filling of the drain, hard and painful swelling of the lower leg,
      pulsatile swelling or mass in the region of the affected joint, are present.
      Definitive confirmation of the diagnosis can be achieved by sonography and
      angiography. The method of treatment consists of simple surgical wound
      exploration and ligation of the affected vessel.

PMID- 16458514
TI  - A genome-wide map of conserved microRNA targets in C. elegans.
AB  - BACKGROUND: Metazoan miRNAs regulate protein-coding genes by binding the 3' UTR
      of cognate mRNAs. Identifying targets for the 115 known C. elegans miRNAs is
      essential for understanding their function. RESULTS: By using a new version of
      PicTar and sequence alignments of three nematodes, we predict that miRNAs
      regulate at least 10% of C. elegans genes through conserved interactions. We have
      developed a new experimental pipeline to assay 3' UTR-mediated
      posttranscriptional gene regulation via an endogenous reporter expression system
      amenable to high-throughput cloning, demonstrating the utility of this system
      using one of the most intensely studied miRNAs, let-7. Our expression analyses
      uncover several new potential let-7 targets and suggest a new let-7 activity in
      head muscle and neurons. To explore genome-wide trends in miRNA function, we
      analyzed functional categories of predicted target genes, finding that one-third
      of C. elegans miRNAs target gene sets are enriched for specific functional
      annotations. We have also integrated miRNA target predictions with other
      functional genomic data from C. elegans. CONCLUSIONS: At least 10% of C. elegans
      genes are predicted miRNA targets, and a number of nematode miRNAs seem to
      regulate biological processes by targeting functionally related genes. We have
      also developed and successfully utilized an in vivo system for testing miRNA
      target predictions in likely endogenous expression domains. The thousands of
      genome-wide miRNA target predictions for nematodes, humans, and flies are
      available from the PicTar website and are linked to an accessible graphical
      network-browsing tool allowing exploration of miRNA target predictions in the
      context of various functional genomic data resources.

PMID- 16458516
TI  - Unicortical transverse osteochondral fracture of the patella: a case report.
AB  - Chondral lesions are relatively common and they usually occur as a result of high
      energy trauma. Chondral fractures of the patella ordinarily occur during an acute
      dislocation of the patella. Patellar chondral fractures without either a
      dislocation or a patella fracture are extremely rare. We have treated a 25-year
      old male who had a unicortical transverse osteochondral fracture of the patella
      without a dislocation which was produced by high energy trauma. Chondral
      fractures of the patella are often overlooked because they are difficult to
      detect on plain radiographs. A persistent cartilaginous irregularity from either
      a chondral or osteochondral fracture may lead to the development of secondary
      osteoarthrosis. In this case, restoration of the articular surface was achieved
      by elevation of the compressed osteochondral fragment. This case demonstrates
      that understanding the mechanism of injury can be helpful in the treatment of
      osteochondral lesions.

PMID- 16458517
TI  - 1,4,9,10-Anthradiquinone as precursor for antitumor compounds.
AB  - 1,4,9,10-Anthradiquinone 5 was reacted with enamines 6 in the Nenitzescu reaction
      to yield unexpected 3,3a,6,12-tetrahydro-3a,7-dihydroxy-2-methyl-6,12-dioxo
      naphtho[2,3-d]indol-1-carboxylates 8A. However, anthracycline-like naphtho
      condensed 5-hydroxyindoles were not obtained from this diquinone. It yielded
      similar reaction products of the Nenitzescu reaction like other quinones
      activated by two electron-withdrawing groups. Furthermore, these new compounds 8A
      were found to constitute precursors for the synthesis of azonines. The conversion
      to dibenzoazonines 13 occurred in an unusual and up to now unknown way consisting
      of isomerization, ring opening, and re-closure. 2-Chloro-anthradiquinone 19
      reacted with enamines 6 as vinylogeous acid chloride to pyrroloanthraquinone 20.
      No substitution of chlorine was observed. Naphtho-condensed indoles 26 were
      obtained by the reactions of unsubstituted 1,4-anthraquinone 25 with enamines 6
      via the normal Nenitzescu route. Indoles 26 were converted to Mannich bases,
      reacting further to dimers by the Diels-Alder reaction of intermediate o-quinone
      methides. Most of the synthesized heterocycles were evaluated for their
      anticancer properties in the NCI's human-disease oriented in vitro anticancer
      screen. Particularly, carbinolamines 8A exhibited inhibitory activity of tumor
      cell growth and thus they constitute a new class of lead structures for
      anticancer drug design.

PMID- 16458518
TI  - Aponeocarzinostatin--a superior drug carrier exhibiting unusually high endurance
      against denaturants.
AB  - The enediyne antitumor antibiotic chromoproteins are very potent in causing DNA
      damages. During the drug delivery time course, the stability of the carrier
      protein becomes an important concern. To simulate conceivably offensive
      environment in biological contexts, such as cell membrane, we studied structural
      endurance of aponeocarzinostatin against several denaturants by circular
      dichroism and nuclear magnetic resonance spectroscopy. For comparison, we also
      examined proteins known to be stable and similar in size to aponeocarzinostatin.
      The results highlight the unusual structural stability of aponeocarzinostatin
      against chemical denaturants, suggesting the potential of aponeocarzinostatin as
      an inherently superior carrier in drug delivery systems.

PMID- 16458519
TI  - Synthesis and CYP26A1 inhibitory activity of 1-[benzofuran-2-yl-(4-alkyl/aryl
      phenyl)-methyl]-1H-triazoles.
AB  - Methodology previously described by our group was applied to the preparation of a
      series of 4-alkyl/aryl-substituted 1-[benzofuran-2-yl-phenylmethyl]-1H-triazoles.
      The [1,2,4]-triazole derivatives were prepared for a range of alkyl and aryl
      substituents, and for the 4-methyl, 4-ethyl, 4-(i)propyl, 4-(t)butyl, 4-phenyl
      and 4-chlorophenyl derivatives, the minor [1,3,4]-triazole isomer also isolated.
      All the triazole derivatives were evaluated for CYP26A1 inhibitory activity using
      a MCF-7 cell-based assay. The 4-ethyl and 4-phenyl-1,2,4-triazole derivatives
      displayed inhibitory activity (IC(50) 4.5 and 7 microM, respectively) comparable
      with that of the CYP26 inhibitor liarozole (IC(50) 7 microM). Using a CYP26A1
      homology model (based on CYP3A4) template, docking experiments were performed
      with MOE with multiple hydrophobic interactions observed in addition to
      coordination between the triazole nitrogen and the haem transition metal.

PMID- 16458520
TI  - Isolation and characterization of a monoamine oxidase B selective inhibitor from
      tobacco smoke.
AB  - It is well established that tobacco smokers have reduced levels of monoamine
      oxidase activities both in the brain and peripheral organs. Furthermore,
      extensive evidence suggests that smokers are less prone to develop Parkinson's
      disease. These facts, plus the observation that inhibition of monoamine oxidase B
      protects against the parkinsonian inducing effects of the nigrostriatal
      neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have prompted studies to
      identify monoamine oxidase inhibitors in the tobacco plant and tobacco cigarette
      smoke. Our previous efforts on cured tobacco leaf extracts have led to the
      characterization of 2,3,6-trimethyl-1,4-naphthoquinone, a non-selective monoamine
      oxidase inhibitor, and farnesylacetone, a selective monoamine oxidase B
      inhibitor. We now have extended these studies to tobacco smoke constituents.
      Fractionation of the smoke extracts has confirmed and extended the qualitative
      results of an earlier report [J. Korean Soc. Tob. Sci.1997, 19, 136]
      demonstrating the inhibitory activity of the terpene trans,trans-farnesol on rat
      brain MAO-B. In the present study, K(i) values for the inhibition of human,
      baboon, monkey, dog, rat, and mouse liver MAO-B have been determined. Noteworthy
      is the absence of inhibitory effects on human placental MAO-A and beef liver MAO
      B. A limited structure-activity relationship study of analogs of trans,trans
      farnesol is reported. Although the health hazards associated with the use of
      tobacco products preclude any therapeutic opportunities linked to smoking, these
      results suggest the possibility of identifying novel structures of compounds that
      could lead to the development of neuroprotective agents.

PMID- 16458521
TI  - Synthesis, docking, and in vitro activity of thiosemicarbazones, aminoacyl
      thiosemicarbazides and acyl-thiazolidones against Trypanosoma cruzi.
AB  - A novel series of thiosemicarbazone and aminoacyl-thiazolidones derivatives were
      synthesized. Their structure suggests that these compounds could have anti
      Trypanosoma cruzi activity. Biological evaluation indicates that some of these
      compounds are able to inhibit the growth of T. cruzi in concentrations non
      cytotoxic to mammalian cells. Docking studies were carried out in order to
      investigate the binding pattern of these compounds for the T. cruzi cruzain (TCC)
      protein, and these showed a significant correlation with experimental data.

PMID- 16458522
TI  - Antifungal properties of new series of quinoline derivatives.
AB  - The series of quinoline derivatives were prepared. The synthetic approach,
      analytical, and spectroscopic data of all synthesized compounds are presented.
      All the prepared derivatives were analyzed using the reversed-phase high
      performance liquid chromatography (RP-HPLC) method for the lipophilicity
      measurement. In the present study, the correlation between RP-HPLC retention
      parameter log K (the logarithm of capacity factor K) and various calculated log P
      data is shown. The relationships between the lipophilicity and the chemical
      structure of the studied compounds are discussed as well. The prepared compounds
      were tested for their in vitro antifungal activity. 2-[(3
      Hydroxyphenylimino)methyl]quinolin-8-ol (8), 2-[(4
      hydroxyphenylimino)methyl]quinolin-8-ol (9) and 2-[(2,5-dichloro-4
      nitrophenylamino)methoxymethyl]quinolin-8-ol (10) showed in vitro antifungal
      activity comparable to or higher than that of the standard fluconazole. Structure
      activity relationships among the chemical structure, the physical properties, and
      the biological activities of the evaluated compounds are discussed in the
      article.

PMID- 16458523
TI  - Morphology of the sternal gland in workers of Coptotermes gestroi (Isoptera,
      Rhinotermitidae).
AB  - The sternal gland is considered the only source of trail pheromones in termites.
      The morphology of the sternal gland was investigated in workers of Coptotermes
      gestroi using transmission and scanning electron microscopy. The results showed a
      small bilobed gland at the anterior part of the fifth abdominal sternite. The
      cuticular surface of the sternal gland showed a V-shaped structure with two peg
      sensilla in elevated socket and various campaniform sensilla. Pores and cuticular
      scale-like protuberances also occur in the glandular area. The ultrastructure
      showed a gland composed of class 1 cells and two different types of class 3 cells
      distinguished by location, different size and electron-density of secretory
      vesicles. Small class 3 cells (type 1) of the anterior lobe are inserted among
      class 1 cells and have weakly electron-dense vesicles associated with
      mitochondria, glycogen and smooth endoplasmic reticulum. The class 3 cells (type
      2) of posterior lobe showed many round electron-lucent vesicles of secretion,
      abundant free ribosomes and a well-developed Golgi apparatus. Each class 3 cell
      is connected to the cuticle by a cuticular duct constituted by the receiving
      canal and the conducting canal. The secretion of class 1 cells is stored in an
      inner subcuticular reservoir that is delimited by the microvilli of these cells.
      This inner reservoir is large and crossed by the campaniform sensilla and ducts
      of two types of class 3 cells that open outside of the insect body. An exterior
      reservoir also is present between the fourth and fifth sternite. The complex
      structure of the sternal gland suggests multicomponents for the trail pheromone
      in the worker of C. gestroi.

PMID- 16458524
TI  - Distribution of chondroitin sulfate in human endometrium.
AB  - Sulfated glycosaminoglycan (GAG) composition was characterized in the human
      endometrium during proliferative and secretory phases of the menstrual cycle.
      Sulfated GAGs were analyzed in endometrium tissue using metachromatic staining,
      biochemical analysis including electrophoresis before and after specific
      enzymatic or chemical degradations, and immunostaining with an antibody against
      chondroitin sulfate (CS). Our results showed that CS was the main sulfated GAG
      species detected, accompanied by small amounts of heparan sulfate and dermatan
      sulfate. CS was distributed overall the connective stroma, around arteriole
      vessels and glands, and there was no important difference in the immunostaining
      between the proliferative and secretory endometrium phases. Our findings extend
      previous observations on the GAG composition in the human endometrium providing
      new information regarding the tissue distribution and location of endometrial CS.

PMID- 16458525
TI  - Radon in a thermal spring: identification of anomalies related to seismic
      activity.
AB  - Anomalies have been observed in the radon content of thermal spring water at the
      Italian-Slovenian border. To distinguish the anomalies caused by environmental
      parameters (air and water temperature, barometric and hydrostatic pressure,
      rainfall) from those ascribed solely to earthquakes with M(L) from 1.2 to 2.5 and
      epicentres, R(E), within 2R(D) (R(D)--Dobrovolsky's radius), two approaches have
      been used: (i) correlation between time gradients of radon concentration and
      hydrostatic pressure, and (ii) regression trees within machine learning programs.
      The regression trees approach has been improved by introducing additional
      environmental parameters and prolonging the measuring period.

PMID- 16458526
TI  - Long-lived Klotho mice: new insights into the roles of IGF-1 and insulin in
      aging.
AB  - It was recently reported by Kurosu et al. that overexpression of Klotho, a newly
      discovered hormone, extends longevity of mice. Because Klotho induces IGF-1 and
      insulin resistance, these findings appear to contradict previous evidence for
      increased life span of dwarf mice with reduced IGF-1 and insulin levels and
      enhanced insulin sensitivity. However, activation of signaling molecules
      downstream from IGF-1 and insulin receptors is reduced in both Klotho and dwarf
      mice, suggesting common mechanisms of delayed aging.

PMID- 16458527
TI  - Tissue-specific roles of IRS proteins in insulin signaling and glucose transport.
AB  - In type 2-diabetes and impaired glucose tolerance, the muscle, fat and liver
      become resistant to insulin, and recent developments place dysregulation of
      insulin receptor substrate (IRS) expression and activation at the center of such
      defects. IRS1 and IRS2 are the major insulin receptor substrates leading to
      glucose homeostasis, and have distinct and overlapping roles in diverse organs.
      The majority of the published literature in this field suggests that IRS1 is the
      major substrate leading to stimulation of glucose transport in muscle and adipose
      tissues, whereas in liver, IRS1 and IRS2 have complementary roles in insulin
      signaling and metabolism.

PMID- 16458528
TI  - FK506, transforming growth factor-beta1 and mesangial matrix synthesis: parallels
      and differences compared with cyclosporine A.
AB  - Cyclosporine A (CsA)-induced glomerulosclerosis is a well-described side effect
      of CsA treatment. Current evidence indicates that FK506 causes similar
      morphologic changes. Recently, we demonstrated that CsA up-regulates the
      expression of transforming growth factor-beta1 (TGF-beta1), its receptors type I
      (TbetaR-I) and type II (TbetaR-II), as well as related matrix protein synthesis
      in mesangial cells (MCs). Here, we assessed the effect of FK506 on the expression
      of TGF-beta1, TbetaR-I, TbetaR-II, fibronectin (FN) and plasminogen activator
      inhibitor type-1 (PAI-1) in MCs. Resting MCs were incubated with/without FK506.
      Time- and concentration-dependent expression was measured at the mRNA and protein
      level. Compared to untreated controls, FK506 stimulated TGF-beta1 mRNA (maximum
      at 8 h, 100 ng/mL: 2.13+/-0.15-fold, P<0.005) and protein expression (maximum at
      96 h, 100 ng/mL: 1.96+/-0.29-fold, P<0.005). In contrast, TbetaR-I and TbetaR-II
      protein expression remained unchanged. Concerning matrix protein synthesis, FK506
      slightly increased FN production (96 h, 100 ng/mL: 1.38+/-0.28-fold, P<0.05), but
      not PAI-1 production. These results indicate that, comparable to CsA, FK506
      induced glomerulosclerosis is also due to a direct effect on mesangial matrix
      production, which is at least in part mediated via up-regulation of TGF-beta1
      expression. The fact that, unlike CsA, FK506 does not increase the expression of
      TbetaR-I, TbetaR-II, and PAI-1, deserves further investigation.

PMID- 16458529
TI  - Ginkgo biloba attenuates mucosal damage in a rat model of ulcerative colitis.
AB  - Intestinal inflammatory states, regardless of specific initiating events, share
      common immunologically mediated pathways of tissue injury and repair. The
      efficacy of various drugs used to treat ulcerative colitis (UC) was investigated.
      The aim of the present study is to evaluate the effects of ginkgo biloba extract
      on the extent and severity of UC caused by intracolonic administration of acetic
      acid in rats. The inflammatory response was assessed by histology and measurement
      of myeloperoxidase activity (MPO), reduced glutathione (GSH), tumor necrosis
      factor (TNF-alpha) and interleukin-1beta (IL-1beta) levels in colon mucosa. Oral
      pretreatment with Ginkgo biloba in doses of (30, 60, 120 mg kg(-1) body weight)
      and sulfasalazine in a dose of (500 mg kg(-1) body weight used as reference) for
      2 days before induction of colitis and continued for 5 consecutive days,
      significantly decreased colonic MPO activity, TNF-alpha, and IL-1beta levels and
      increased GSH concentration. Moreover, Ginkgo biloba attenuated the macroscopic
      colonic damage and the histopathological changes-induced by acetic acid. These
      results suggest that Ginkgo biloba may be effective in the treatment of UC
      through its scavenging effect on oxygen-derived free radicals.

PMID- 16458530
TI  - Activation processes and polyethylene formation on a phillips model catalyst
      studied by laser ablation, laser desorption, and static secondary ion mass
      spectrometry.
AB  - Since the discovery of the Phillips catalysts, there still is much uncertainty
      concerning their activation, their molecular structure, the nature of the active
      chromium sites, and the polymerization mechanisms. Surface techniques are not
      easy to be used for such study according to the nonconductive behavior of the
      support. Therefore, model Phillips catalyst is elaborated by spin coating a
      trivalent chromium precursor on a silicon wafer. The surface characterization of
      this model catalyst is conducted by laser ablation mass spectrometry (LA-MS),
      laser desorption/ionization mass spectrometry (LDI-MS), and static secondary ion
      mass spectrometry (s-SIMS), at different steps of its preparation. To validate
      our approach, a comparison is also made between the model and the real Philips
      catalyst. Moreover, the model catalyst efficiency for polyethylene synthesis is
      evaluated and allows us to discuss the validity of the mechanisms previously
      proposed to explain the catalytic process. The characterization of Phillips model
      catalyst by mass spectrometry allows us to better understand the activation
      processes of such catalyst. Depending on the activation temperature, chromium
      oxide species are formed and anchored at the support surface. They consist mainly
      in mono-chromium sites at high temperature. The chromium valence is hexavalent.
      This model catalyst is active for the polymerization of ethylene. A pseudo
      oligomer molecular weight distribution is observed by LA-MS, whereas s-SIMS
      allows us to elucidate the anchorage of the polymer at activate chromium surface
      sites.

PMID- 16458531
TI  - Efficient calculation of accurate masses of isotopic peaks.
AB  - This paper presents a new method for calculating accurate masses of isotopic
      peaks. It is based on breaking the calculation into a binary series of
      calculations. The molecule is built up by a series of such calculations. At each
      step the accurate masses are calculated as a probability weighted sum of the
      masses of the contributing peaks. The method is computationally efficient and
      accurate for both mass and relative abundance.

PMID- 16458533
TI  - Antigen-specific regulatory T cells--ex vivo expansion and therapeutic potential.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) are critical for the regulation
      of tolerance and have shown enormous potential in suppressing pathological immune
      responses in autoimmune disease, transplantation, and graft-versus-host disease
      (GVHD). Recent data indicate that suppression of organ-specific autoimmunity is
      critically dependent on the antigen specificity of the Treg. An emerging model of
      Treg action is that organ-specific Treg acquire suppressive activity through
      activation by dendritic cells expressing organ-derived antigens. Thus, efficacy
      of Treg-based therapy should be increased by using organ-specific Treg rather
      than polyclonal Treg. This necessitates the ability to identify relevant antigens
      and to expand rare antigen-specific Treg from diverse polyclonal populations.
      Here, we consider the importance of antigen specificity in Treg function and
      discuss recent advances for the expansion of antigen-specific Treg and the
      therapeutic potential of Treg in controlling autoimmunity and GVHD.

PMID- 16458534
TI  - CD4+CD25+ regulatory T lymphocytes in bone marrow transplantation.
AB  - Induction of immunological tolerance to alloantigens would be the treatment of
      choice to prevent graft-versus-host disease (GvHD) and allograft rejection in
      transplantation medicine. Organisms use a variety of mechanisms to avoid
      potentially deadly immunity to self-antigens. The most potent self-tolerance
      mechanism is probably dominant tolerance assured by regulatory and suppressor T
      lymphocytes. It appears therefore attractive to use the same mechanism to induce
      transplantation-tolerance. We here review and discuss recent advances in the use
      of one of the best-characterized regulatory T lymphocyte populations,
      CD4(+)CD25(+) T cells, to prevent graft-versus-host disease and bone marrow
      allograft rejection.

PMID- 16458536
TI  - GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout
      the CNS.
AB  - Once thought to merely act as scaffolds in neuronal migration, recent evidence
      suggests that radial glia may serve as progenitors for the majority of neurons in
      the CNS. Cre/loxP fate-mapping experiments were carried out using a fragment of a
      glial-specific promoter (glial fibrillary acidic protein; GFAP) to drive
      expression of Cre recombinase. We show that GFAP+ progenitor cells give rise to
      neurons and oligodendrocytes throughout the CNS. We find very little regional
      heterogeneity in the neurogenic potential of radial glia between dorsal and
      ventral telencephalon. Additionally, radial glia serve as precursors for
      subpopulations of interneurons in the ventral telencephalon. Interestingly, the
      human GFAP promoter but not the mouse GFAP promoter is active in oligodendrocyte
      progenitor cells. We also demonstrate that the most commonly used Cre reporter
      lines are very inefficient in detecting Cre-dependent recombination in astrocytes
      and describe a new Cre reporter line for assessing recombination in astrocytes.

PMID- 16458537
TI  - Attenuated demyelination in the absence of the macrophage-restricted adhesion
      molecule sialoadhesin (Siglec-1) in mice heterozygously deficient in P0.
AB  - Mouse mutants heterozygously deficient for the myelin component P0 mimic some
      forms of inherited neuropathies in humans. We have previously shown that both T
      lymphocytes and macrophages contribute to the demyelinating neuropathy. Both cell
      types appear to influence each other mutually, i.e., impaired T lymphocyte
      development in RAG-1-deficient P0 mutants leads to decreased macrophage numbers
      and retarded macrophage activation causes reduced T lymphocyte numbers in the
      peripheral nerves of P0(+/-) mice. In the present study, we investigated the
      possible role of the macrophage-restricted sialic acid-binding Ig-like lectin
      sialoadhesin (Sn, Siglec-1) in the pathogenesis of inherited demyelination in
      P0(+/-) mice. We found that most peripheral nerve macrophages express Sn in the
      mutants. Myelin mutants devoid of Sn show reduced numbers of CD8+ T lymphocytes
      and macrophages in peripheral nerves and less severe demyelination, resulting in
      improved nerve conduction properties. Our findings are potentially important in
      the development of future treatment strategies for inherited demyelinating
      neuropathies.

PMID- 16458538
TI  - Beverage intake, diabetes, and glucose control of adults in America.
AB  - PURPOSE: Beverages are important components of diet and a route for the intake of
      caffeine, ethanol, and other bioactive substances. The aim of the study is to
      examine the association between type of beverages consumed and glucose control in
      American adults with and without diabetes. METHODS: Diabetes status, glycosylated
      hemoglobin (hemoglobin A1c [HbA1c]) level, and 1-month recall food frequency
      questionnaires were all collected in the Third National Health and Nutrition
      Examination Survey (1988 to 1994), based on a nationally representative sample of
      the noninstitutionalized civilian US population. We used regression and other
      methods for clustered data to examine the association of HbA1c levels with self
      reported intake of carbonated drinks, alcohol, coffee, tea, juices, and milk in
      participants aged 18 to 75 years with and without diabetes. RESULTS: Adults with
      diabetes reported drinking half the amount of alcohol as adults without diabetes.
      Compared with nondrinkers, subjects who had 30 or more drinks per month of
      alcohol had mean HbA1c levels 1.2 units less (p < 0.001) in persons with diabetes
      and 0.2% less (p < 0.001) in persons without diabetes. Adults with diabetes
      reported drinking three times as much diet soda as adults without diabetes.
      However, in adults with diabetes who had one or more drinks of diet soda per day,
      HbA1c level was 0.7 units greater (p < 0.001) compared with those who drank none.
      CONCLUSIONS: Alcohol consumption, at least in moderate amounts, correlates with
      better glucose control. There is a correlation between drinking diet soda and
      glucose control in adults with diabetes.

PMID- 16458539
TI  - Racial discrimination and the incidence of hypertension in US black women.
AB  - PURPOSE: Unique experiences associated with "race," such as racism, may adversely
      affect health. Our goal is to assess whether racism is associated with the
      occurrence of hypertension in African-American women. METHODS: In the first
      prospective examination of perceived experiences of racism in relation to the
      incidence of hypertension, we used data from the Black Women's Health Study, a
      follow-up study of US black women that began in 1995. The 1997 follow-up
      questionnaire contained eight questions designed to measure personally mediated
      racism and institutionalized racism. Cox proportional hazard models were used to
      estimate incidence rate ratios (IRRs), with control for age, body mass index, and
      questionnaire period. RESULTS: There were 2316 incident cases of hypertension
      reported during 104,574 person-years of observation from 1997 to 2001. Most women
      reported experiences of racism. In the total sample, IRRs for the association of
      racism with incident hypertension were close to the null. However, some positive
      associations were observed for personally mediated racism in women born outside
      the United States. CONCLUSIONS: There may be an increase in hypertension
      associated with experiences of racism in certain subgroups of African-American
      women.

PMID- 16458540
TI  - Effects of 60-Hz magnetic field exposure on nocturnal 6-sulfatoxymelatonin,
      estrogens, luteinizing hormone, and follicle-stimulating hormone in healthy
      reproductive-age women: results of a crossover trial.
AB  - PURPOSE: Exposure to residential magnetic fields may disrupt the normal nocturnal
      rise in melatonin levels, resulting in increased risk for breast cancer, possibly
      through increased levels of reproductive hormones. We investigated whether
      exposure to a 60-Hz magnetic field under controlled conditions is associated with
      a decrease in urinary nocturnal 6-sulfatoxymelatonin level and increase in
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen levels
      in healthy premenopausal women. METHODS: Using a crossover design, half the
      participants were assigned to magnetic field exposure of 5 to 10 mG greater than
      ambient levels for 5 consecutive nights during the early to midluteal phase of
      the menstrual cycle. On the last night of exposure, a nocturnal urine sample was
      collected. The next month, participants were sham exposed. The other half of
      participants were assigned the reverse order of exposure. RESULTS: Magnetic field
      exposure was associated with decreased 6-sulfatoxymelatonin levels, but no
      changes in reproductive hormone levels were observed. Participants using
      prescription medications and anovulatory participants had more pronounced
      decreases in 6-sulfatoxymelatonin levels with magnetic field exposure.
      CONCLUSION: This study provides further evidence that exposure to magnetic fields
      is associated with decreased nocturnal melatonin levels, but does not support the
      hypothesis that such exposure results in increased urinary levels of estrogens,
      LH, or FSH.

PMID- 16458541
TI  - Safety and feasibility of percutaneous autologous skeletal myoblast
      transplantation in the coil-infarcted swine myocardium.
AB  - INTRODUCTION: Autologous skeletal myoblast transplantation (ASMT) for myocardial
      regeneration is a promising new treatment for patients with congestive heart
      failure secondary to myocardial infarction (MI). However, non-surgical delivery
      could broaden the utility of this approach. The present study was designed to
      evaluate the safety and feasibility of transplanting autologous skeletal myoblast
      (ASM) via endovascular delivery into the infarcted swine myocardium. METHODS:
      Seven female Yorkshire swine successfully underwent induced left ventricular MI.
      ASM biopsies were obtained from the hind limb of each animal and myoblasts were
      expanded in vitro. In a pilot experiment, ASM were labeled with iridium and short
      term retention and biodistribution was determined 2 h after ASM delivery via the
      MyoStar needle-injection catheter inserted through the femoral artery. At 30 days
      post-infarction, the remaining animals were divided into three groups containing
      2 animals each for percutaneous catheter delivery into the infarcted zone: group
      1 control animals were injected with media only, group 2 and 3 animals were
      injected with approximately 300 x 10(6) and 600 x 10(6) ASM, respectively. Sixty
      days post-transplantation, the swine hearts were harvested. RESULTS: During the
      60-day period between transplantation and harvest, no adverse events were
      recorded, and continuous rhythm monitoring revealed no arrhythmias. In the small
      sampling size, myocardial function assessments revealed a trend toward
      improvement in the treatment groups with respect to ejection fraction, viability,
      and cardiac index. However, histology of treated swine hearts identified no
      skeletal muscle cells. DISCUSSION: Percutaneous ASMT into an infarcted swine
      myocardium is feasible and safe, and may contribute to overall improved heart
      function.

PMID- 16458542
TI  - Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug
      resistance protein-1 dependent way: an in vitro study.
AB  - We have explored the action of zoledronic acid, which has an apoptotic effect and
      is used as an agent for treating skeletal metastases and osteoporosis, in the
      presence of vinblastine, and whether this effect is associated with MRP-1
      (multidrug resistance protein-1) expression. HEK (human embryonic kidney) 293
      cells were transfected to form the multidrug resistant cell line designated
      293MRP (MRP-1 expressing HEK293 cells). Both lines were treated with varying
      concentrations of vinblastine and zoledronic acid. Apoptosis was determined by
      the TUNEL (deoxyuridine triphosphate nick end-labeling) method. The type of
      treatment, MRP-1 expression status, and the type of treatment with respect to MRP
      1 expression status significantly affected (P < 0.001) the degree of apoptosis.
      The largest increase in cytotoxicity was noted in HEK293 cells, when 100 micromol
      zoledronic acid was added to 4 microg/ml vinblastine (an increment of 80.3%, P <
      0.001). This preliminary work shows that zoledronic acid acts synergistically
      with vinblastine to induce apoptosis in an MRP-1 dependent way.

PMID- 16458543
TI  - Induction and activity-dependent reversal of persistent LTP and LTD in lateral
      perforant path synapses in vivo.
AB  - The reversibility of long-term potentiation (LTP) and heterosynaptic long-term
      depression (LTD) lasting weeks was examined in the lateral perforant path of
      freely moving adult Sprague-Dawley rats. LTP lasting weeks was rapidly reversed
      within minutes by high-frequency heterosynaptic stimulation of the medial
      perforant path, in an N-methyl-D-aspartate receptor-dependent manner. LTP
      reversal also occurred, albeit more slowly and to a lesser extent, when animals
      were given 1-3 weeks of overnight exposure to an enriched environment (EE). LTD
      likewise was reversed upon repeated EE exposure. A covert similarity between the
      degrees of LTP and LTD reversal was revealed when the small potentiation effect
      of EE treatment by itself on lateral path responses was taken into account.
      Despite its ability to reverse previously acquired synaptic plasticity, two weeks
      of EE treatment had no effect on animals' retention of the platform location in a
      spatial watermaze task, although it did facilitate new learning. These data are
      in agreement with the hypothesis that hippocampal synapses retain the capacity
      for rapid synaptic change even when otherwise relatively stable plasticity has
      previously been induced. Slow reversal of such plasticity did not correlate with
      a loss of memory retention, possibly because either slow changes permit
      reorganization of representations such that both old and new information can be
      accommodated, or else the new information is synaptically represented in
      orthogonal fashion to the old information.

PMID- 16458544
TI  - Enhancement of extinction memory consolidation: the role of the noradrenergic and
      GABAergic systems within the basolateral amygdala.
AB  - Evidence from previous studies indicates that the noradrenergic and GABAergic
      influences within the basolateral amygdala (BLA) modulate the consolidation of
      memory for fear conditioning. The present experiments investigated whether the
      same modulatory influences are involved in regulating the extinction of fear
      based learning. To investigate this issue, male Sprague Dawley rats implanted
      with unilateral or bilateral cannula aimed at the BLA were trained on a
      contextual fear conditioning (CFC) task and 24 and 48 h later were given
      extinction training. Immediately following each extinction session they received
      intra-BLA infusions of the GABAergic antagonist bicuculline (50 ng), the beta
      adrenocepter antagonist propranolol (500 ng), bicuculline with propranolol,
      norepinephrine (NE) (0.3, 1.0, and 3.0 microg), the GABAergic agonist muscimol
      (125 ng), NE with muscimol or a control solution. To investigate the involvement
      of the dorsal hippocampus (DH) as a possible target of BLA activation during
      extinction, other animals were given infusions of muscimol (500 ng) via an
      ipsilateral cannula implanted in the DH. Bilateral BLA infusions of bicuculline
      significantly enhanced extinction, as did infusions into the right, but not left
      BLA. Propranolol infused into the right BLA together with bicuculline blocked the
      bicuculline-induced memory enhancement. Norepinephrine infused into the right BLA
      also enhanced extinction, and this effect was not blocked by co-infusions of
      muscimol. Additionally, muscimol infused into the DH did not attenuate the memory
      enhancing effects of norepinephrine infused into the BLA. These findings provide
      evidence that, as with original CFC learning, noradrenergic activation within the
      BLA modulates the consolidation of CFC extinction. The findings also suggest that
      the BLA influence on extinction is not mediated by an interaction with the dorsal
      hippocampus.

PMID- 16458545
TI  - Effect of two prednisone exposures on mood and declarative memory.
AB  - Corticosteroids are essential for life and an integral part of the stress
      response. However, in excess, corticosteroids can be associated with a variety of
      effects on the brain including hippocampal atrophy and even neuronal death, mood
      changes, and declarative memory impairment. The magnitude of mood change in
      patients receiving prednisone is reportedly associated with previous lifetime
      corticosteroid exposure, consistent with a sensitization or kindling process
      whereby greater effects are observed with repeated exposure. To our knowledge,
      the effect of multiple corticosteroid exposures on mood and memory has not been
      previously examined prospectively in animals or humans. In this study, 30 human
      volunteers, with no history of systemic prescription corticosteroid therapy, were
      given (in random order using a crossover design) two 3-day exposures of
      prednisone (60 mg/day) and one of identical placebo, with 11-day washouts between
      each medication exposure. Before and after each 3-day prednisone/placebo
      exposure, declarative memory was assessed using different versions of the Rey
      Auditory Verbal Learning Test (RAVLT) to minimize practice or learning effects,
      while mood was assessed with the 21-item Hamilton Rating Scale for Depression,
      Young Mania Rating Scale and Internal State Scale. No significant mood changes
      were found. However, a significant decrease in aspects of RAVLT performance was
      observed after the first prednisone exposure consistent with a decline in
      declarative memory performance. The decline in RAVLT performance was
      significantly smaller after the second prednisone exposure as compared to the
      initial prednisone exposure. Thus, a second prednisone exposure was associated
      with an attenuated prednisone-effect on declarative memory. These data suggest
      tolerance or habituation, rather than sensitization, to prednisone effects on
      declarative memory during a second exposure. Implications and possible
      explanations for the findings are discussed.

PMID- 16458547
TI  - Intra-abdominal hypertension and abdominal compartment syndrome following surgery
      for ruptured abdominal aortic aneurysm.
AB  - OBJECTIVES: To investigate the importance of intra-abdominal hypertension (IAH)
      and abdominal compartment syndrome (ACS), based on the December 2004 consensus
      definition, on outcome after surgery for ruptured abdominal aortic aneurysm
      (rAAA). METHODS: Twenty-seven patients underwent open surgery for rAAA after the
      introduction of intra-abdominal pressure (IAP) measurements among patients at
      risk of IAH. Case-records were reviewed retrospectively. Seventeen patients
      underwent IAP-monitoring. RESULTS: Of eight patients with IAP <21 mmHg none
      developed colonic ischaemia or ACS. Of four patients with IAP 21-25 mmHg (IAH
      grade III), two underwent colonic resection. One patient treated with open
      abdomen died from cardiac arrhythmia. Five patients had IAP >25 mmHg (IAH grade
      IV). All developed ACS. Two were not decompressed and both developed pulmonary
      complications, one died. Two underwent colonic resection and one was treated with
      open abdomen, all three survived. Of 10 patients not monitored for IAP, one died
      of cardiac complications, but no patient developed signs of colonic ischaemia or
      ACS. Mortality at 30 days and 1 year was 3/27 (11%). CONCLUSION: IAH and ACS were
      common among patients undergoing surgery for rAAA. The ACS consensus definition
      seems appropriate in this clinical context. Monitoring IAP, and timely
      decompression of patients with IAH might improve outcome after surgery for rAAA.

PMID- 16458546
TI  - An audit demonstrating a reduction in MRSA infection in a specialised vascular
      unit resulting from a change in infection control protocol.
AB  - INTRODUCTION: In 2003, 18% of all admissions to our vascular ward were colonised
      by MRSA, with an MRSA infection rate of 10.6%. Standard practice was to segregate
      patients with proven MRSA from the rest of the patient pool. After a prospective
      audit, regression analysis was used to identify factors that could stratify
      patients into high and low risk for MRSA colonisation. A change in isolation
      policy was introduced that segregated patients according to their risk of MRSA
      acquisition, and isolated all patients undergoing prosthetic vascular
      reconstruction. Antibiotic policy was also altered. This audit reports the impact
      of these changes on MRSA colonisation and infection rates. METHODS: The MRSA
      status of patients during 777 in-patient episodes was prospectively recorded
      during three time spans; period 1 (November 2002-April 2003) before the change in
      isolation and antibiotic policy and, periods 2 (August-December 2003) and 3
      (October 2004-January 2005) after the change in policy. RESULTS: Hospital
      acquired MRSA colonisation was reduced from 10.6% in period 1, to 1.1 and 1.4% in
      periods 2 and 3, respectively (p<0.001). Similarly, MRSA infection rates fell
      from 10.6 to 2.9 and 0.9% over the same time frame (p<0.001). The most dramatic
      changes in MRSA infection rates occurred in patients undergoing aneurysm repair
      (MRSA infection 30.1% in period 1 vs. 3.9 and 2.9% in periods 2 and 3) and lower
      limb revascularization (31 vs. 0 vs. 4.2%). Stepwise regression analysis revealed
      that the system of isolation was a significant factor reducing MRSA infection and
      colonisation rates (p<0.001). CONCLUSIONS: These data demonstrate that a change
      in infection control policy can significantly reduce MRSA infection in a vascular
      unit.

PMID- 16458548
TI  - Iliofemoral deep vein thrombosis in childhood; developing a management protocol.
AB  - OBJECTIVE: To develop an evidence-based protocol for the management of
      iliofemoral deep vein thrombosis (IDVT) in childhood. METHODS: A search of the
      literature was undertaken. All publications pertaining to IDVT in childhood were
      analysed and then categorised according to their level of evidence.
      Recommendations were then made on the basis of this. RESULTS: The commonest
      presenting symptoms were pain and swelling in the affected limb (evidence level
      II). Predisposing risk factors of special significance in children included the
      recent use of a venous access device, malignancy, prothrombotic disorders,
      infection, surgery and congenital venous anomalies (evidence level II). The most
      frequently described imaging modalities were B-mode ultrasonography, duplex,
      venography, and helical CT (evidence level III). The mainstay of treatment was
      anticoagulation with LMWH alone or followed by warfarin (evidence level I). Early
      clot removal through catheter-directed thrombolysis or surgical thrombectomy has
      been shown to be beneficial (evidence level II/III). There is little evidence for
      the benefit of early mobilisation and compression therapy in childhood.
      CONCLUSION: Level I evidence relating to IDVT in childhood is sparse. The
      possibility of IDVT should be considered when examining a child with a swollen
      and painful limb. Imaging should be with duplex ultrasound, followed by spiral CT
      to include assessment of the IVC. A thrombophilia screen should be taken prior to
      anticoagulation with LMWH (and warfarin). Thrombolysis should be considered in
      cases of extensive IDVT.

PMID- 16458549
TI  - NO trapping in biological systems with a functionalized zeolite network.
AB  - Zeolite-Y powder has been functionalized with ferric iron-diethyldithiocarbamate
      complexes and applied to trap nitric oxide radicals in liquids and biological
      systems. The complexes have been assembled in situ in the pores of zeolite-Y and
      act as traps for nitric oxide radicals. The resulting mononitrosyl-iron complexes
      form a mixture of diamagnetic ferric and paramagnetic ferrous complexes. The
      yield of trapped NO may be determined ex situ using electron paramagnetic
      resonance. The material may be anchored on solid surfaces, mixed into a composite
      or compressed into small pellets. The material was used to detect endogenous NO
      in endothelial cell cultures and spinach leaves. The sensitivity of the
      functionalized zeolite is significantly better than that achieved in conventional
      trapping of NO with iron-diethyldithiocarbamate complexes.

PMID- 16458550
TI  - Being a parent of the adolescent with complex chronic pain: an interpretative
      phenomenological analysis.
AB  - BACKGROUND: Previous quantitative research has shown that parents of adolescents
      with chronic pain report elevated levels of emotional distress in addition to
      limitations in social and family functioning. AIM: This study aimed to further
      explore this parental impact by employing qualitative methodology to investigate
      parental experiences of caring for an adolescent with chronic pain. METHODS: A
      sample of 17 parents/carers of adolescents with chronic pain was selected from
      two UK tertiary clinic sites. Participants were 11 mothers, five fathers, and one
      grandmother (primary caregiver). Four focus groups with parents/carers were
      conducted to discuss the impact of caring for an adolescent with chronic pain on
      the parent/carer. Transcripts were analysed using interpretative phenomenological
      analysis (IPA). FINDINGS: Data analysis revealed two superordinate themes that
      captured the extensive, and largely negative, impact of being a parent of an
      adolescent with chronic pain. These themes were labelled 'struggle for control
      and coherence' and 'a very different life'. Both themes represent a fundamental
      parental struggle to adapt to a life very different than expected, a life fraught
      with uncertainty, fear, distress and loss. CONCLUSIONS: Parents who are unable to
      achieve the relief of their adolescent's chronic pain and suffering report
      significant personal distress that is exemplified by the repetitive search for
      legitimacy of their child's pain in 'diagnosis'. In the absence of diagnosis
      parents reported an unwelcome suspension in an unusual pattern of parenting,
      resembling the infant phase of parenting.

PMID- 16458551
TI  - Faithful estimation of dynamics parameters from CPMG relaxation dispersion
      measurements.
AB  - This work examines the robustness of fitting of parameters describing
      conformational exchange (k(ex), p(a/b), and Deltaomega) processes from CPMG
      relaxation dispersion data. We have analyzed the equations describing
      conformational exchange processes for the intrinsic inter-dependence of their
      parameters that leads to the existence of multiple equivalent solutions, which
      equally satisfy the experimental data. We have used Monte-Carlo simulations and
      fitting to the synthetic data sets as well as the direct 3-D mapping of the
      parameter space of k(ex), p(a/b), and Deltaomega to quantitatively assess the
      degree of the parameter inter-dependence. The demonstrated high correlation
      between parameters can preclude accurate dynamics parameter estimation from NMR
      spin-relaxation data obtained at a single static magnetic field. The strong
      parameter inter-dependence can readily be overcome through acquisition of spin
      relaxation data at more than one static magnetic field thereby allowing accurate
      assessment of conformational exchange properties.

PMID- 16458552
TI  - Automatic atom type and bond type perception in molecular mechanical
      calculations.
AB  - In molecular mechanics (MM) studies, atom types and/or bond types of molecules
      are needed to determine prior to energy calculations. We present here an
      automatic algorithm of perceiving atom types that are defined in a description
      table, and an automatic algorithm of assigning bond types just based on atomic
      connectivity. The algorithms have been implemented in a new module of the AMBER
      packages. This auxiliary module, antechamber (roughly meaning "before AMBER"),
      can be applied to generate necessary inputs of leap-the AMBER program to generate
      topologies for minimization, molecular dynamics, etc., for most organic
      molecules. The algorithms behind the manipulations may be useful for other
      molecular mechanical packages as well as applications that need to designate atom
      types and bond types.

PMID- 16458553
TI  - Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD:
      discordant in vitro and in vivo dose-effects: a review.
AB  - In order to develop efficient therapeutic regimes for chronic obstructive
      pulmonary disease (COPD), N-acetylcysteine (NAC) has been tested as a medication
      which can suppress various pathogenic processes in this disease. Besides its well
      known and efficient mucolytic action, NAC meets these needs by virtue of its
      antioxidant and anti-inflammatory modes of action. NAC is a thiol compound which
      by providing sulfhydryl groups, can act both as a precursor of reduced
      glutathione and as a direct ROS scavenger, hence regulating the redox status in
      the cells. In this way it can interfere with several signaling pathways that play
      a role in regulating apoptosis, angiogenesis, cell growth and arrest and
      inflammatory response. Overall, the antioxidant effects of NAC are well
      documented in in vivo and in vitro studies. It successfully inhibits oxidative
      stress at both high and low concentrations, under acute (in vitro) and chronic
      administration (in vivo). With regard to its anti-inflammatory action, in
      contrast, the effects of NAC differ in vivo and in vitro and are highly dose
      dependent. In the in vitro settings anti-inflammatory effects are seen at high
      but not at low concentrations. On the other hand, some long-term effectiveness is
      reported in several in vivo studies even at low dosages. Increasing the dose
      seems to improve NAC bioavailability and may also consolidate some of its
      effects. In this way, the effects that are observed in the clinical and in vivo
      studies do not always reflect the success of the in vitro experiments.
      Furthermore, the results obtained with healthy volunteers do not always provide
      incontrovertible proof of its usefulness in COPD especially when number of
      exacerbations and changes in lung function are chosen as the primary outcomes.
      Despite these considerations and in view of the present lack of effective
      therapies to inhibit disease progression in COPD, NAC and its derivatives,
      because of their multiple molecular modes of action, remain promising medication
      once doses and route of administration are optimized.

PMID- 16458554
TI  - Changes in sperm motility in response to osmolality/Ca2+ in three Indonesian
      fresh water teleosts: goby (Oxyeleotris marmorata), Java carp (Puntius
      javanicus), and catfish (Clarias batrachus).
AB  - Sperm of most fresh water teleosts become motile when released into the hypotonic
      fresh water environment, but the role of osmolality and Ca2+ on sperm motility is
      not clear. Osmotic pressure and Ca2+ concentrations increase from fresh water to
      brackish water. Java carp Puntius javanicus and catfish Clarias batrachus live
      and reproduce only in fresh water. On the other hand, goby Oxyeleotris marmorata
      can acclimate and reproduce from fresh water to brackish water. In the present
      study, sperm motility and trajectory were compared among these three Indonesian
      endemic species. Sperm of Java carp, goby, and catfish begun to move in the
      hypotonic condition (< 200 mOsm/kg). However, the response to Ca2+ was different
      among these teleosts. In the presence of Ca2+, Java carp sperm swam in circular
      paths and immediately become quiescent, suggesting that Java carp sperm motility
      is activated in hypotonic aquatic environment without Ca2+. Goby sperm swam
      straightforward in the presence or absence of Ca2+. Percentages of motile sperm
      increased in 100-200 mOsm/kg but suppressed by removal of Ca2+. Regarding sperm
      motility and trajectory, no response was found in catfish sperm. These results
      suggest that a response to Ca2+ is different among sperm of the three species and
      suited to their habitat.

PMID- 16458555
TI  - Late onset of NMDA receptor-mediated ventilatory control during early development
      in zebrafish (Danio rerio).
AB  - Increased ventilation frequency (fV) in response to hypoxia in adult fish depends
      on ionotropic N-methyl-D-aspartate (NMDA) receptors. Nonetheless, the ontogeny of
      central control mechanisms mediating hypoxic ventilatory chemoreflexes in lower
      vertebrates has not been studied. Therefore, the aim of this study was to
      determine when the hypoxic ventilatory response during zebrafish (Danio rerio)
      development is mediated via NMDA receptors, by performing physiological
      experiments and western blot analysis of NMDA receptor subunits. Zebrafish larvae
      at stages 4-16 days post-fertilisation (dpf) were exposed to an hypoxic pulse in
      control groups and in groups treated with MK801 (NMDA receptor antagonist). The
      hypoxic increase in fV was present at all larval stages, and it matured during
      development. The reflex became MK801 sensitive at 8 dpf, but did not completely
      rely on a glutamatergic transmission until 13 dpf. This, together with changing
      subunit composition during the different stages (increasing amounts of NMDAR1
      subunits and appearance of NMDAR2A subunits in adults), suggests that the amount
      of functional NMDA receptors needed to achieve a fully developed reflex is not
      attained until later stages. Furthermore, our results suggest that other non-NMDA
      receptor mechanisms are responsible for the hypoxia-induced increase in fV during
      the earlier developmental stages.

PMID- 16458556
TI  - Energetics and thermoregulation during digging in the rodent tuco-tuco (Ctenomys
      talarum).
AB  - For subterranean rodents, searching for food by extension of the tunnel system
      and maintenance of body temperature are two of the most important factors
      affecting their life underground. In this study we assess the effect of ambient
      temperature on energetics and thermoregulation during digging in Ctenomys
      talarum. We measured VO2 during digging and resting at ambient temperature (Ta)
      below, within, and above thermoneutrality. Digging metabolic rate was lowest at
      Ta within the thermoneutral zone and increased at both lower and higher
      temperatures, but body temperature (Tb) remained constant at all Tas. Below
      thermoneutrality, the cost of digging and thermoregulation are additive. Heat
      production for thermoregulation would be compensated by heat produced as a by
      product of muscular activity during digging. Above thermoneutrality, conduction
      would be an important mechanism to maintain a constant Tb during digging.

PMID- 16458557
TI  - The hearing abilities of the silver carp (Hypopthalmichthys molitrix) and bighead
      carp (Aristichthys nobilis).
AB  - Concern regarding the spread of silver carp (Hypopthalmichthys molitrix) and
      bighead carp (Aristichthys nobilis) through the Illinois River has prompted the
      development of a Bio-acoustic Fish Fence (BAFF) to act as an acoustic fish
      deterrent. The application of this technology has resulted in a need to
      understand the auditory physiology of the target species, in order to maximise
      the effect of the barrier in preventing the migration of the non-indigenous carp
      species into Lake Michigan, whilst minimising the effect on indigenous fish
      populations. Therefore, the hearing thresholds of 12 H. molitrix and 12 A.
      nobilis were defined using the Auditory Brainstem Response (ABR) technique, in a
      pressure-dominated sound field generated by submerged transducers of the type
      used in the construction of the BAFF system. The results clearly show that these
      fish are most sensitive to sounds in a frequency bandwidth of between 750 Hz and
      1500 Hz, with higher thresholds below 300 Hz and above 2000 Hz.

PMID- 16458558
TI  - Molecular cloning and characterization of growth hormone receptor and its
      homologue in the Japanese eel (Anguilla japonica).
AB  - Two cDNAs encoding growth hormone receptor (GHR)-like genes, eGHR1 and eGHR2,
      were isolated from Japanese eel (Anguilla japonica) liver tissue. The putative
      eel GHR proteins showed conserved structural features of vertebrate GHRs,
      including six cysteine residues and a YGEFS motif in the extracellular domain, a
      single transmembrane region, and proline-rich box 1 and box 2 domains. Northern
      blot analysis showed a single eGHR1 transcript in liver, while two sizes of eGHR2
      transcripts, thought to be produced by alternative splicing, were present. RT-PCR
      revealed that eGHR1 and eGHR2 transcripts were widely distributed throughout the
      whole body of the Japanese eel. Moreover, the results of binding assays showed
      the specific binding of growth hormone to recombinant eGHR1. Since these putative
      eGHR proteins show all characteristics of the GHR family, we conclude that eGHR1
      and eGHR2 cDNA encode two different GHRs in Japanese eel. We confirmed the ligand
      specificity of eGHR1 by binding assay, and further research is needed to allow
      characterization of the binding capability of eGHR2.

PMID- 16458559
TI  - 17Beta-hydroxysteroid dehydrogenase (17beta-HSD) in scleractinian corals and
      zooxanthellae.
AB  - Steroid metabolism studies have yielded evidence of 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) activity in corals. This project was undertaken to
      clarify whether there are multiple isoforms of 17beta-HSD, whether activity
      levels vary seasonally, and if zooxanthellae contribute to activity. 17Beta-HSD
      activity was characterized in zooxanthellate and azooxanthellate coral fragments
      collected in summer and winter and in zooxanthellae cultured from Montipora
      capitata. More specifically, 17beta-HSD activity was characterized with regard to
      steroid substrate and inhibitor specificity, coenzyme specificity, and Michaelis
      constants for estradiol (E2) and NADP+. Six samples each of M. capitata and
      Tubastrea coccinea (three summers, three winters) were assayed with E2 and NADP+.
      Specific activity levels (pmol/mg protein) varied 10-fold among M. capitata
      samples and 6-fold among T. coccinea samples. There was overlap of activity
      levels between summer and winter samples. NADP+/NAD+ activity ratios varied from
      1.6 to 22.2 for M. capatita, 2.3 to 3.8 for T. coccinea and 0.7 to 1.1 for
      zooxanthellae. Coumestrol was the most inhibitory of the steroids and
      phytoestrogens tested. Our data confirm that corals and zooxanthellae contain
      17beta-HSD and are consistent with the presence of more than one isoform of the
      enzyme.

PMID- 16458561
TI  - Isolation and characterization of a trypsin fraction from the pyloric ceca of
      chinook salmon (Oncorhynchus tshawytscha).
AB  - A trypsin fraction was isolated from the pyloric ceca of New Zealand farmed
      chinook salmon (Oncorhynchus tshawytscha) by ammonium sulfate fractionation,
      acetone precipitation and affinity chromatography. The chinook salmon enzyme
      hydrolyzed the trypsin-specific synthetic substrate benzoyl-DL-arginine-p
      nitroanilide (DL-BAPNA), and was inhibited by the general serine protease
      inhibitor phenyl methyl sulfonyl fluoride (PMSF), and also by the specific
      trypsin inhibitors - soybean trypsin inhibitor (SBTI) and benzamidine. The enzyme
      was active over a broad pH range (from 7.5 to at least pH 10.0) at 25 degrees C
      and was stable from pH 4.0 to pH 10.0 when incubated at 20 degrees C, with a
      maximum at pH 8.0. The optimum temperature for the hydrolysis of DL-BAPNA by the
      chinook salmon enzyme was 60 degrees C, however, the enzyme was unstable at
      temperatures above 40 degrees C. The molecular mass of the chinook salmon trypsin
      was estimated as 28 kDa by SDS-PAGE.

PMID- 16458560
TI  - Astacin family metallopeptidases and serine peptidase inhibitors in spider
      digestive fluid.
AB  - Digestive fluid of the araneid spider Argiope aurantia is known to contain zinc
      metallopeptidases. Using anion-exchange chromatography, size-exclusion
      chromatography, sucrose density gradient centrifugation, and gel electrophoresis,
      we isolated two lower-molecular-mass peptidases, designated p16 and p18. The N
      terminal amino acid sequences of p16 (37 residues) and p18 (20 residues) are 85%
      identical over the first 20 residues and are most similar to the N-terminal
      sequences of the fully active form of meprin (beta subunits) from several
      vertebrates (47-52% and 50-60% identical, respectively). Meprin is a peptidase in
      the astacin (M12A) subfamily of the astacin (M12) family. Additionally, a 66
      residue internal sequence obtained from p16 aligns with the conserved astacin
      subfamily domain. Thus, at least some spider digestive peptidases appear related
      to astacin of decapod crustaceans. However, important differences between spider
      and crustacean metallopeptidases with regard to isoelectric point and their
      susceptibility to hemolymph-borne inhibitors are demonstrated. Anomalous behavior
      of the lower-molecular-mass Argiope peptidases during certain fractionation
      procedures indicates that these peptidases may take part in reversible
      associations with each other or with other proteins. A. aurantia digestive fluid
      also contains inhibitory activity effective against insect digestive peptidases.
      Here we present evidence for at least thirteen, heat-stable serine peptidase
      inhibitors ranging in molecular mass from about 15 to 32 kDa.

PMID- 16458562
TI  - Use of androgenesis for estimating maternal and mitochondrial genome effects on
      development and oxygen consumption in rainbow trout, Oncorhynchus mykiss.
AB  - Chromosome set manipulation was used to produce rainbow trout, Oncorhynchus
      mykiss, with identical nuclear backgrounds, but different maternal backgrounds to
      determine mitochondrial effects on development rate and oxygen consumption.
      Significant differences in development rate and oxygen consumption were observed
      between groups from different females. Development rates ranged from a mean of
      317.97 degree days ( degrees d) to 335.25 degrees d in progeny from different
      females. Mean oxygen consumption rates ranged from 3.31 micromol O2 g(-1) wet
      mass h(-1) to 9.66 micromol O2 g(-1) wet mass h(-1). Oxygen consumption and
      development rate analysis revealed the two slowest developing groups had the
      highest oxygen consumption rates. Development rate differences between second
      generation clonal females indicate that mitochondrial genomes play a significant
      role on early development and are comparable to development rate differences
      between clonal lines of rainbow trout. These results indicate that selection for
      mitochondrial genomes could increase growth rates and possibly food conversion
      ratios in aquaculture species.

PMID- 16458563
TI  - An outbreak of aseptic meningitis due to echovirus 30 associated with attending
      school and swimming in pools.
AB  - OBJECTIVES: To identify the risk factors of an outbreak of meningitis associated
      with echovirus 30-infection that occurred in Rome, Italy, in late 1997 among
      children from two different schools. METHODS: A case-control study was carried
      out. A case was defined as a child from either of the two schools, A or B, who
      presented meningitis-like (fever, headache and vomiting), diarrhea, or
      respiratory tract symptoms. All asymptomatic students were included in the
      analysis as controls. RESULTS: Among 446 pupils (80%) who answered the
      questionnaire, 68 met the case definition. Twenty pupils developed a meningitis
      like illness. Echovirus 30 was isolated from cerebrospinal fluid (CSF) in four
      and from stools in six. Forty-eight pupils reported other symptoms. The attack
      rate was 10.8% in school A and 0.8% in school B for meningitis-like illness; it
      was 12% and 10%, respectively, for other enterovirus-like illnesses. The risk of
      meningitis-like illness was higher among children attending school A (crude OR =
      14.9; 95% CI = 4.3-52.1), among children using any public pool (OR = 3.8; 95% CI
      = 1.5-9.9) and those using an outside swimming pool X (OR=13.4; 95% CI=2.7-65.8
      versus no swimming pool and OR = 8.3; 95% CI = 1.1-62.6 versus other pools). The
      epidemic curve appears to suggest a person-to-person transmission. CONCLUSIONS:
      The epidemic occurred by person-to-person transmission in a number of classrooms
      and at swimming pool X.

PMID- 16458564
TI  - Etiology and epidemiology of diarrhea in children in Hanoi, Vietnam.
AB  - OBJECTIVES: This paper provides a preliminary picture of diarrhea with regards to
      etiology, clinical symptoms, and some related epidemiologic factors in children
      less than five years of age living in Hanoi, Vietnam. METHODS: The study
      population included 587 children with diarrhea and 249 age-matched healthy
      controls. The identification of pathogens was carried out by the conventional
      methods in combination with ELISA, immunoseparation, and PCR. The antibiotic
      susceptibility was determined by MIC following the NCCLS recommendations.
      RESULTS: Of those with diarrhea, 40.9% were less than one year old and 71.0% were
      less than two years old. A potential pathogen was identified in 67.3% of children
      with diarrhea. They were group A rotavirus, diarrheagenic Escherichia coli,
      Shigella spp, and enterotoxigenic Bacteroides fragilis, with prevalences of
      46.7%, 22.5%, 4.7%, and 7.3%, respectively. No Salmonella spp or Vibrio cholerae
      were isolated. Rotavirus and diarrheagenic E. coli were predominant in children
      less than two years of age, while Shigella spp, and enterotoxigenic B. fragilis
      were mostly seen in the older children. Diarrheagenic E. coli and Shigella spp
      showed high prevalence of resistance to ampicillin, chloramphenicol, and to
      trimethoprim/sulfamethoxazole. Children attending the hospitals had fever
      (43.6%), vomiting (53.8%), and dehydration (82.6%). Watery stool was predominant
      with a prevalence of 66.4%, followed by mucous stool (21.0%). The mean episodes
      of stools per day was seven, ranging from two to 23 episodes. Before attending
      hospitals, 162/587 (27.6%) children had been given antibiotics. Overall, more
      children got diarrhea in (i) poor families; (ii) families where piped water and a
      latrine were lacking; (iii) families where mothers washed their hands less often
      before feeding the children; (iv) families where mothers had a low level of
      education; (v) families where information on health and sanitation less often
      reached their households. CONCLUSIONS: Group A rotavirus, diarrheagenic
      Escherichia coli, Shigella spp, and enterotoxigenic Bacteroides fragilis play an
      important role in causing diarrhea in children in Hanoi, Vietnam. Epidemiological
      factors such as lack of fresh water supply, unhygienic septic tank, low family
      income, lack of health information, and low educational level of parents could
      contribute to the morbidity of diarrhea in children.

PMID- 16458565
TI  - An important public health problem: rabies suspected bites and post-exposure
      prophylaxis in a health district in Turkey.
AB  - OBJECTIVE: The aim of this study was to describe rabies suspected animal bites
      and post-exposure prophylaxis (PEP) practices in Narlidere District in Turkey
      between 1999 and 2001. METHODS: One thousand five hundred and sixty-nine rabies
      suspected bite cases reported were identified from the District's rabies
      surveillance forms. RESULTS: Males comprised 66.7% of the cases, and 43.5% of the
      total were under 20 years old. In 74% of cases the animal involved in the bite
      was a dog. Only 70% of the animals had an owner, and only 17% of the animals had
      a rabies vaccination certificate. In terms of treatment, 68% of the human cases
      received PEP, and 21% of cases had an extra (sixth) vaccination dose, which is a
      substantial burden on the healthcare system, costing half a million US dollars
      per year. The place where the bite occurred (rural areas), the age of the
      recipient (more than 10 years old), the animal type (animals other than dogs and
      cats), lack of a vaccination certificate for the animal, and place of wound
      treatment (hospital) were significantly associated with PEP application.
      CONCLUSIONS: In addition to the currently recommended strategy of controlling the
      dog population and of vaccinating domesticated animals, adults and children
      should be educated about bite prevention to reduce the number of animal bites.

PMID- 16458566
TI  - Frequency of isolation of pathogens from nosocomial bloodstream infection in a
      tertiary referral hospital in the United Arab Emirates.

PMID- 16458567
TI  - Comparison of two numerical approaches for bone remodelling.
AB  - This paper addresses the "checkerboard" phenomenon, which occurs in numerical
      simulation of bone remodelling. It attempts to answer the question: is an element
      based approach suitable for bone remodelling? Two different numerical approaches,
      the element-based and the node-based finite element analyses, are implemented
      using ABAQUS. A comparison of the numerical results demonstrates that the
      checkerboard phenomenon occurs only in the element-based finite element analyses;
      the node-based approach eradicates the checkerboard phenomenon but requires much
      more computational time. This study shows that it is essential to enforce the
      continuity of bone density across the element boundaries. As the node-based
      approach requires much more computational time, the first-order Adams-Bashforth
      integration method is introduced to reduce computational cost. The comparisons
      with Euler's forward method demonstrate that the first-order Adams-Bashforth
      method indeed enhances accuracy and reduces computational cost. This study
      concludes that the node-based approach with the first-order Adams-Bashforth
      integration scheme is to be recommended for computational bone remodelling
      studies.

PMID- 16458568
TI  - Axial cyclic behavior of the bone-screw interface.
AB  - Screw fixation strength is investigated by using a pullout test. Despite many
      screw pullout studies, the effects of loading rate on the pullout behavior of
      pedicle screws are not known. The objective of this study was to assess the
      effects of loading rate on the pullout stiffness and strength of pedicle screws.
      Sixty pedicle screws were inserted in foam blocks and pulled out at four
      different rates: 0.1, 1, 5 and 50 mm/min. Twenty of these 60 screws were cycled
      non-destructively at four different rates sequentially, i.e., 0.1, 1, 5 and 50
      mm/min prior to pullout. Ten additional pedicle screws were inserted in five calf
      lumbar vertebrae, cycled as in foam group, and pulled out at a rate of either 0.1
      or 50 mm/min. The results showed that the stiffness was higher at all rates
      compared to 0.1 mm/min in foam model but in bone model only 1 and 5 mm/min groups
      were higher compared to 0.1 mm/min. The pullout strength in 50 mm/min group was
      higher than that in 0.1 mm/min group in both foam and bone model. The results
      suggested that loading rate influenced the mechanics of the bone-screw interface.
      Therefore, a fair comparison between the pullout studies can be achieved under
      same loading rate conditions. Moreover, the cycling of the pedicle screws in
      axial direction within a pre-yield region showed an unusual hysteresis curve.
      Further studies are needed for a better understanding of the mechanics of the
      screw-bone interface.

PMID- 16458569
TI  - Human neoplastic mesothelial cells express voltage-gated sodium channels involved
      in cell motility.
AB  - Given the pivotal role of ion channels in neoplastic transformation, the aim of
      the present study has been to assess possible differences in the expression
      patterns of voltage-gated monovalent cationic (Na(+) and K(+)) currents between
      normal and neoplastic mesothelial cells (NM, MPM, respectively), and to evaluate
      the role of specific ion channels in mesothelioma cells proliferation, apoptosis,
      and motility. To achieve this aim, membrane currents expressed in NM and MPM
      cells derived from surgically-removed human specimens were investigated by means
      of patch-clamp electrophysiology. NM cells were found to express three main
      classes of K(+) currents, which were defined as K(IR), maxiK(Ca), and K(V)
      currents on the basis of their biophysical and pharmacological properties. Each
      of these K(+) currents was absent in MPM cells; by contrast, MPM cells revealed
      the novel appearance of tetrodotoxin (TTX)-sensitive voltage-gated Na(+) currents
      undetected in normal mesothelial cells. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) and real-time PCR analysis of MPM cells transcripts showed
      significant expression of the mRNAs encoding for Na(V)1.2, and Na(V)1.6, and
      Na(V)1.7 (and less so for Na(V)1.3, Na(V)1.4, and Na(V)1.5) main voltage-gated
      sodium channel (VGSC) alpha-subunit(s). Interestingly, blockade of VGSCs with TTX
      decreased mesothelioma cell migration in in vitro motility assays; on the other
      hand, TTX failed to interfere with cell viability, proliferation, and apoptosis
      progression triggered by UV exposure. In summary, the results of the present
      study suggest that VGSCs expression in MPM cells may favor the increased motility
      of the neoplastic cells, a phenotypic feature often associated with the malignant
      phenotype.

PMID- 16458570
TI  - Dysplasia/neoplasia surveillance in oral lichen planus patients: a description of
      clinical criteria adopted at a single centre and their impact on prognosis.
AB  - The concept of dysplasia/neoplasia surveillance has been applied to long-standing
      conditions associated with an increased risk of cancer. Although still
      controversial, periodic direct clinical examination as well as endoscopic
      techniques are currently performed in patients with inflammatory bowel diseases,
      Barrett's esophagus, and melanocytic skin lesions in order to detect and treat
      dysplastic or early malignant changes and therefore improve the patients'
      prognosis. It is not known if patients with oral lichen planus (OLP), a chronic
      inflammatory condition associated with an increased risk of cancer development,
      might benefit from such surveillance as well, nor how this should be performed.
      Here we present the clinical criteria we have adopted over a 12-year period to
      detect early malignant transformation of OLP, and report on their impact on the
      management and prognosis of patients. Overall data from 45 patients affected by
      117 neoplastic events arising from OLP have been evaluated. Our
      dysplasia/neoplasia surveillance has led us to diagnose most episodes (94.9%; n.:
      111) of OLP malignant transformation in early intraepithelial and microinvasive
      phases, namely stage 0 and I oral cancers (T(is) N0M0 or T1N0M0). The 5-year
      survival rate, where applicable, has been 96.7%. Advanced stage oral cancers have
      been diagnosed in six patients, three of whom have died. We suggest that the
      application of strict and rigorous clinical criteria in dysplasia/neoplasia
      surveillance could help clinicians to detect and treat early OLP malignant
      transformation and therefore improve long-term survival rates. Nevertheless, a
      small subgroup of patients has been shown not to benefit from such surveillance
      and to be characterized by a rapid development of advanced-stage oral carcinomas,
      with consequent poor prognosis.

PMID- 16458571
TI  - Potential applications of oral brush cytology with liquid-based technology:
      results from a cohort of normal oral mucosa.
AB  - Fifty healthy volunteers were studied to assess the potential applications of
      oral brush sampling using liquid-based cytology. Three specimens from the buccal
      mucosa and lateral border of tongue were collected from each subject by using
      cervical brushes and brooms. The brush was immersed in a preservative fluid. The
      sample in the preservative fluid was processed according to the manufacturer's
      directions (SurePath, UK). Slides were stained by the Papanicolaou method and
      assessed for squamous cell adequacy by the same criteria used for cervical
      cytology screening. Immunocytochemical staining for FHIT (Fragile Histidine
      Triad) was applied in liquid-based preparations following the streptavidin-biotin
      peroxidase method. Human papillomavirus (HPV) detection was performed using the
      Hybrid Capture 2 assay (Digene) and the PCR-based Roche AMPLICOR HPV Test. LBC
      preparation slides showed good sample preservation, specimen adequacy and
      visualization of cell morphology. Interestingly, nine cases showed borderline
      cytological abnormalities from apparently normal oral mucosa. All cases showed
      good quality positive FHIT immunoreactivity staining. All studied cases were high
      risk HPV negative using HC2 assay method. However, the AMPLICOR Roche Test
      detected four samples with positive results for high-risk HPVs. Liquid-based
      cytology has potential as a screening tool for oral cancer and precancer. The
      method may also have applications for research and practice in the field of oral
      cancer and precancer. However a special custom-designed oral cytobrush is
      required.

PMID- 16458572
TI  - Genetics and functional genomics of legume nodulation.
AB  - Gram-negative soil bacteria (rhizobia) within the Rhizobiaceae phylogenetic
      family (alpha-proteobacteria) have the unique ability to infect and establish a
      nitrogen-fixing symbiosis on the roots of leguminous plants. This symbiosis is of
      agronomic importance, reducing the need for nitrogen fertilizer for
      agriculturally important plants (e.g. soybean and alfalfa). The establishment of
      the symbiosis involves a complex interplay between host and symbiont, resulting
      in the formation of a novel organ, the nodule, which the bacteria colonize as
      intracellular symbionts. This review focuses on the most recent discoveries
      relating to how this symbiosis is established. Two general developments have
      contributed to the recent explosion of research progress in this area: first, the
      adoption of two genetic model legumes, Medicago truncatula and Lotus japonicus,
      and second, the application of modern methods in functional genomics (e.g.
      transcriptomic, proteomic and metabolomic analyses).

PMID- 16458573
TI  - Advances in maize genomics: the emergence of positional cloning.
AB  - Positional cloning has been and remains a powerful method for gene identification
      in Arabidopsis. With the completion of the rice genome sequence, positional
      cloning in rice also took off, including the cloning of several quantitative
      trait loci. Positional cloning in cereals such as maize whose genomes are much
      larger than that of rice was considered near impossible because of the vast
      amounts of repetitive DNA. However, conservation of synteny across the cereal
      genomes, in combination with new maize resources, has now made positional cloning
      in maize feasible. In fact, a chromosomal walk is usually much faster than the
      more traditional method of gene isolation in maize by transposon tagging.

PMID- 16458574
TI  - Length control of extended protein structures in bacteria and bacteriophages.
AB  - The length of the tail of bacteriophages is controlled by a protein which acts as
      a molecular ruler. The needle of the injectisome, which is assembled by the
      polymerization of subunits that are exported through the nascent injectisome, is
      functionally related to the tail of bacteriophages. Interestingly, its length is
      controlled by a protein, which is itself exported and acts as a molecular ruler
      that is coupled to a substrate specificity switch. The bacterial flagellum is
      evolutionarily related to the injectisome. The length of the hook is also
      controlled by a secreted protein. This protein acts as a substrate specificity
      switch and, possibly, also as a ruler.

PMID- 16458575
TI  - Automatic fitting to 'powder' EPR spectra of coupled paramagnetic species
      employing Feynman's theorem.
AB  - A previous automatic fitting procedure of EPR spectra has been extended with the
      purpose to characterise coupled paramagnetic complexes in powders and frozen
      solutions. The theoretical EPR spectra were obtained by matrix diagonalization of
      a general spin Hamiltonian. A least-squares fitting procedure using analytical
      derivatives of the calculated spectrum with respect to the spectroscopic, fine
      structure, nuclear quadrupole, electron-electron, and hyperfine coupling tensors
      was used to refine those parameters. The powder spectra of matrix isolated *CF3
      and RCF2CF2* radicals, previously measured at low temperature, were reanalysed
      with this method. A theoretically modeled complex consisting of a Cu2+ ion,
      featuring an axially symmetric g-tensor and 63Cu hyperfine structure anisotropy,
      and a free radical located at different orientations, with respect to the
      symmetry axis of the Cu2+ ion, was examined in order to investigate the
      possibility to recover the magnetic parameters of the separate units and the
      magnetic couplings between them.

PMID- 16458576
TI  - High luminescence quantum yields and long luminescence lifetime from Eu(III)
      complex containing two crystal water based on a new beta-diketonate ligand.
AB  - New members of family of Eu(III) complex based on the thenoylacetophenone have
      been synthesized and characterized. The compounds were found for high metal
      luminescence quantum yields and long luminescence lifetime, especially for
      compound with two crystal water, corresponding with other compounds containing
      two crystal water. The result is attributed to high molar absorption coefficients
      of the Eu(III) complex according to UV-vis and emission spectra. The high molar
      absorption coefficients balance quenching effect from OH oscillators of water
      contained in compound.

PMID- 16458577
TI  - Indirect spectrophotometric determination of arbutin, whitening agent through
      oxidation by periodate and complexation with ferric chloride.
AB  - A simple and accurate spectrophotometric method for the determination of arbutin
      (glycosylated hydroquinone) is described. It is based on the oxidation of arbutin
      by periodate in presence of iodate. Excess periodate causes liberation of iodine
      at pH 8.0. The unreacted periodate is determined by measurement of the liberated
      iodine spectrophotometrically in the wavelength range (300-500 nm). A calibration
      curve was constructed for more accurate results and the correlation coefficient
      of linear regression analysis was -0.9778. The precision of this method was
      better than 6.17% R.S.D. (n=3). Regression analysis of Bear-Lambert plot shows
      good correlation in the concentration range 25-125 ug/ml. The identification
      limit was determined to be 25 ug/ml a detailed study of the reaction conditions
      was carried out, including effect of changing pH, time, temperature and volume of
      periodate. Analyzing pure and authentic samples containing arbutin tested the
      validity of the proposed method which has an average percent recovery of 100.86%.
      An alternative method is also proposed which involves a complexation reaction
      between arbutin and ferric chloride solution. The produced complex which is
      yellowish-green in color was determined spectophotometrically.

PMID- 16458578
TI  - NMR investigation of methyl-2,4-dimethoxysalicylate: effect of solvent and
      temperature.
AB  - (1)H NMR and (13)C NMR of methyl-2,4-dimethoxysalicylate 2 was measured in
      chloroform-d at the temperature range of 220-330 K, in dimethyl sulfoxide-d(6) at
      the temperature range of 300-400 K and in a polar protic solvent (CD(3)OD) at 300
      K. The structure of 2 in liquid phase (solvent) is compared with those in solid
      phase (X-ray) and in the gas phase (quantum mechanical calculations). The
      relationship between molecular geometry, (1)H NMR chemical shift and W coupling
      of involved protons has a complex nature, but hydrogen bonds [C=O...H-O and
      C=O...H-CH(2)O] strength is the principle factor.

PMID- 16458579
TI  - A simple method to synthesize triangular silver nanoparticles by light
      irradiation.
AB  - We describe a simple method to synthesize triangular silver nanoparticles by
      photoreducing the silver ions by citrate. A noteworthy difference of the present
      method as compared with the previous photo-induced methods is that good shape
      control over the nanoparticles can be realized in the absence of soft templates
      or polymer directing agents. The formation process of the silver nanoparticles
      was investigated by UV-vis spectroscopy and transmission electron microscopy
      (TEM). It was found that the concentration of reactant plays important role in
      the morphology control of produced silver nanoparticles. As one of the
      applications of these nanoparticles, they were used as surface-enhanced Raman
      scattering substrates and 1,4-bis[2-(4-pyridyl)ethenyl]-benzene (BVPP) was used
      as a Raman probe to evaluate the enhancement ability of the triangular silver
      nanoparticles.

PMID- 16458580
TI  - An infrared and resonance Raman spectroscopic study of phenylazonaphthol
      pigments.
AB  - The IR, resonance Raman (RR) and electronic spectra of two phenylazonaphthol
      pigments, LRC Scarlet and 4BL Red, have been measured and assignments of the
      vibrational and electronic spectra were facilitated by ab initio calculation s at
      the B3-LYP/DZ level. Vibrational spectra indicate that the major species in the
      solid state are the hydrazo tautomers. Electronic spectra are in accordance with
      the nature of the electronic transitions predicted by time-dependent B3-LYP/DZ
      calculations.

PMID- 16458581
TI  - Resonance Raman study of free-base tetraphenylporphine and its dication.
AB  - Resonance Raman spectra of free-base tetraphenylporphine and its dication
      obtained with 441.6, 476.5, 488.0 and 514.5 nm excitation lines in the frequency
      region 100-1625 cm(-1) are reported. Some bands due to in-plane and out-of-plane
      vibrational modes, which are symmetry forbidden under ideal D(2h), are also seen
      in the Raman spectra of these molecules. These bands arise due to dynamic and/or
      static coupling of out-of-plane modes with the allowed in-plane modes. Dynamic
      coupling may be facilitated by the proton tunneling, while static coupling is due
      to out-of-plane distortion in the geometrical structure of the molecule. Shift in
      the positions for certain bands in the Raman spectra of dication are interpreted
      on the basis of electronic changes due to sharing of electrons of the B(1u)
      orbital by the two added protons.

PMID- 16458582
TI  - Tetragonal distortions of some tetragonal Cr3+ centers in fluoroperovskite ABF3
      crystals.
AB  - The tetragonal distortions [characterized by the displacement DeltaR of the F(-)
      ion intervening in Cr(3+) and V(B) (B(2+) vacancy) or M(+) ion in B(2+) site] for
      Cr(3+)-V(B) and Cr(3+)-Li(+) centers in Cr(3+)-doped fluoroperovskites KBF(3)
      (B=Mg, Zn) and ACdF(3) (A=K, Rb, Cs) and also for Cr(3+)-Na(+) center in KZnF(3)
      have been studied by calculating the EPR parameters D, g(parallel) and
      g(perpendicular) from the crystal-field theory. From the studies, an interesting
      trend is suggested, i.e., when the size of the co-doped monovalent impurity M(+)
      in the nearest neighbor B(2+) site is comparable to that of the replaced B(2+)
      ion, the displacement DeltaR of the intervening F(-) ion in Cr(3+)-M(+) center is
      smaller than that in Cr(3+)-V(B) center and if the M(+) iron is much smaller or
      much larger than that of the replaced B(2+) ion, the displacement DeltaR in
      Cr(3+)-M(+) center is greater than that in Cr(3+)-V(B) center. The causes of the
      trend are discussed.

PMID- 16458583
TI  - Single site electronic spectroscopy of free base octaethylporphyrin,
      octaethychlorin and their diacids in n-octane at 298K and 7K.
AB  - Single site fluorescence and absorption spectra of free base octaethylporphyrin,
      octaethylchlorin and their respective diacids in n-octane at 298 K and 7 K are
      reported. Vibrational frequencies associated with the ground and excited states
      were determined from the spectra. All of these moieties exhibit well defined and
      narrow spectral features, with the exception of the octaethylchlorin diacid; it
      gives broad spectral bands even at 7 K. Respective Q and B origins were also
      identified.

PMID- 16458584
TI  - Polarised IR-microscope spectra of guanidinium hydrogensulphate single crystal.
AB  - Polarised IR-microscope spectra of C(NH(2))(3)*HSO(4) small single crystal
      samples were measured at room temperature. The spectra are discussed on the basis
      of oriented gas model approximation and group theory. The stretching nuOH
      vibration of the hydrogen bond with the Ocdots, three dots, centeredO distance of
      2.603A gives characteristic broad AB-type absorption in the IR spectra. The
      changes of intensity of the AB bands in function of polariser angle are
      described. Detailed assignments for bands derived from stretching and bending
      modes of sulphate anions and guanidinium cations were performed. The observed
      intensities of these bands in polarised infrared spectra were correlated with
      theoretical calculation of directional cosines of selected transition dipole
      moments for investigated crystal. The vibrational studies seem to be helpful in
      understanding of physical and chemical properties of described compound and also
      in design of new complexes with exactly defined behaviors.

PMID- 16458585
TI  - Photoinduced intermolecular electron transfer from dimethyl aniline to 7-amino
      coumarin dyes in the surface of beta-cyclodextrin.
AB  - The photoinduced electron-transfer reaction between Coumarin dyes and N,N
      dimethylaniline has been investigated using steady-state and Time-resolved
      fluorescence spectroscopy in the surface of beta-cyclodextrin in dimethyl
      formamide (DMF) solvent. The electron-transfer rate constant has been correlated
      with the free-energy change during the process. We have observed a diffusion
      controlled ET process in pure DMF by showing a normal Marcus region. However, the
      picture is different in presence of cyclodextrin. Here the ET is retarded at
      higher free-energy region. This unusual feature in bimolecular electron-transfer
      reaction is assumed to be arising from the different binding possibility of the
      Coumarin molecules to the cyclodextrin moity.

PMID- 16458586
TI  - Theoretical studies of lattice distortions around the impurity ions in V2+ doped
      CdCl2, CdI2 and PbI2.
AB  - The lattice distortions around the impurity ions in V(2+) doped CdCl(2), CdI(2)
      and PbI(2) are theoretically studied from the perturbation formulas of the spin
      Hamiltonian (SH) parameters zero-field splitting, g factors and the hyperfine
      structure constants for a 3d(3) ion in trigonal symmetry based on the cluster
      approach. In these formulas, the contributions from the s-orbitals of the ligands
      are taken into account. Based on the studies, it is found that the local angles
      beta (between the impurity-ligand bonding lengths and the C(3) axis) in the
      impurity centers are smaller than the angles beta(H) in the hosts. The calculated
      SH parameters based on the above local angles beta show better agreement than
      those on neglecting of the ligand s-orbital contributions (and those on the host
      angles beta(H)) with the experimental data.

PMID- 16458587
TI  - Theoretical studies of the spin Hamiltonian parameters and local structures for
      Cs3CoX5 (X = Cl, Br).
AB  - The spin Hamiltonian (SH) parameters (zero-field splitting D and anisotropic g
      factors g(||) and g( perpendicular)) and local structures for Cs(3)CoX(5) (X =
      Cl, Br) are theoretically studied from the perturbation formulas of the SH
      parameters for a 3d(7) ion in tetragonally distorted tetrahedra based on the
      cluster approach. In these formulas, both the contributions from the crystal
      field (CF) mechanism and those from the charge-transfer (CT) mechanism are taken
      into account. It is found that the [CoX(4)](2-) clusters are slightly elongated
      and the tetragonal distortion angles Deltatheta(=theta-theta(0), where theta(0)
      equals to approximately 54.74 degrees is the bonding angle related to the C(4)
      axis in regular tetrahedra) are about -1.68 degrees and -1.71 degrees for X = Cl
      and Br, respectively. The calculated SH parameters as well as the effective
      magnetic moments based on the above angles are in reasonable agreement with the
      observed values. From the studies, the importance of the contributions to the SH
      parameters from the CT mechanism increases with increasing the spin-orbit
      coupling coefficient of the ligand, i.e., Cl(-) < Br(-). The results are compared
      with those obtained from the conventional crystal-field model in the previous
      works.

PMID- 16458588
TI  - Reduced expression and functional impairment of Toll-like receptor 2 on dendritic
      cells in chronic hepatitis C virus infection.
AB  - BACKGROUND: Dendritic cells (DCs) utilize Toll-like receptors (TLRs) to sense
      virus and initiate immune responses. We aimed at elucidating the roles of TLRs on
      DCs in hepatitis C virus (HCV) infection. METHODS: Monocyte-derived DCs were
      obtained from 32 healthy volunteers (HV) and 30 chronically HCV-infected patients
      (CH). TLR2, TLR3 and TLR4 expressions on immature DCs were quantified by real
      time quantitative RT-PCR. We stimulated DCs with specific TLR ligands and
      examined DC maturation, cytokine production and ability to stimulate allogeneic
      CD4(+) T cells. RESULTS: TLR2 expression on immature DCs was lower in the CH
      group, whereas those of TLR3 or TLR4 were not different between the groups. Each
      TLR ligand induced DC maturation and stimulated them to release comparable levels
      of IL-12p70, IL-6, IL-10, TNF-alpha and IFN-beta between the groups. TLR2 and
      TLR4 ligands enhanced DC ability to stimulate T cell proliferation, with the
      degree due to the TLR2 ligand being lower in the CH group. CONCLUSIONS: In HCV
      infection, the TLR2 expression on DCs is reduced and TLR2-stimulated DCs show
      lesser ability to proliferate T cells than healthy counterparts, suggesting that
      the TLR2 system is involved in HCV-induced immunopathogenesis.

PMID- 16458589
TI  - Ten-year analysis of adenovirus type 7 molecular epidemiology in Korea, 1995
      2004: implication of fiber diversity.
AB  - BACKGROUND: Adenovirus type 7 (Ad7) is frequently responsible for severe
      respiratory infections, especially in young infants. Since the Ad7 epidemics have
      been associated with severe childhood pneumonia and significant mortality in
      Korea, 1995-1999, continuous surveillance was necessary for Ad7 related diseases.
      OBJECTIVES: To characterize epidemiologic features of Ad7 in 1995-2004, genetic
      diversity of Ad7 were studied by determining genome types (GTs) and the fiber
      diversity. STUDY DESIGN: A total of 139 Ad7 strains were obtained from Korean
      children with pneumonia. Serotype specificity was confirmed by
      microneutralization assay. GTs were determined by restriction analysis with 12
      enzymes. The variable region of the fiber was sequenced. RESULTS: Two GTs, Ad7d
      (N=98, 71%) and Ad7l (N=41, 29%) have been identified. In 1995-1996 and 2001
      2002, Ad7d was dominant accounting for 98-100% of all Ad7; in 1999-2000, Ad7l was
      the prevalent GT accounting for 100% of all Ad7; in 1997-1998 and 2003-2004, both
      GTs circulated concurrently. The change in the relative predominance of GT
      occurred in 2 or 3 years. The Lys substitution for Arg at codon 280 of the fiber
      was identified in 31 Ad7d strains (32%) while no variations were observed among
      Ad7l. It was noteworthy that two fiber variants of Ad7d were not concurrently
      prevalent on any time after 1996. The shift in predominant fiber variants of Ad7d
      was also observed in 2-3 years. CONCLUSIONS: Our data demonstrated that the two
      GTs, Ad7d and Ad7l circulated in an alternating manner between outbreaks of Ad7
      associated childhood pneumonia over 10 consecutive years in Korea. Fiber
      diversity at position 280 within Ad7d appeared to contribute to the annual
      distribution of Ad7d. This observation necessitates further studies to
      demonstrate an association between fiber variation and host cell specificity or
      neutralization antibody recognition.

PMID- 16458590
TI  - High throughput quantification of cholesterol and cholesteryl ester by
      electrospray ionization tandem mass spectrometry (ESI-MS/MS).
AB  - Analysis of free cholesterol (FC) is not well suited for electrospray ionization
      (ESI); however, cholesteryl ester (CE) form ammonium adducts in positive ion mode
      and generate a fragment ion of m/z 369 upon collision-induced fragmentation. In
      order to allow parallel analysis of FC and CE using ESI tandem mass spectrometry
      (ESI-MS/MS), we developed an acetyl chloride derivatization method to convert FC
      to cholesteryl acetate (CE 2:0). Derivatization conditions were chosen to provide
      a quantitative conversion of FC to CE 2:0 without transesterification of
      naturally occurring CE species. FC and CE were analyzed by direct flow injection
      analysis using a fragment of m/z 369 in a combination of selected reaction
      monitoring (SRM) and precursor ion scan for FC and CE, respectively.
      Quantification was achieved using deuterated D(7)-FC and CE 17:0/CE 22:0 as
      internal standards as well as calibration lines generated by addition of FC and
      naturally occurring CE species to the respective sample matrix. The developed
      assay showed a precision and detection limit sufficient for routine analysis. A
      run time of 1.3 min and automated data analysis allow high throughput analysis.
      Loading of human skin fibroblast and monocyte derived macrophages with stable
      isotope labeled FC showed a potential application of this method in metabolism
      studies. Together with existing mass spectrometry methodologies for lipid
      analysis, the present methodology will provide a useful tool for clinical and
      biochemical studies and expands the lipid spectrum that can be analyzed from one
      lipid sample on a single instrumental platform.

PMID- 16458591
TI  - Effects of interleukin-15 on lipid oxidation: disposal of an oral [(14)C]
      triolein load.
AB  - Interleukin 15 (IL-15) has previously been shown to have important effects on
      lipid metabolism in adipose tissue, particularly influencing the rate of the de
      novo fatty acid synthesis. The results presented here show that chronic
      administration to rats (100 microg/kg body weight) has important effects on the
      metabolic fate of an exogenous [(14)C]-triolein load, decreasing the
      incorporation of lipid into adipose tissue and significantly increasing the total
      (14)CO(2) formation from [(14)C]-triolein. Skeletal muscle and possibly liver
      seem to be the main organs involved in the action of IL-15 on lipid oxidation,
      since the presence of the cytokine in incubated EDL muscle with [(14)C]-palmitic
      acid increased (14)CO(2) formation by 39%. Concerning the mechanism, the results
      suggest that the transport of fatty acids into mitochondria could be involved in
      the action of IL-15 since the cytokine clearly increases the presence of L-CPT-I
      and CPT-II in liver tissue. In addition, IL-15 treatment resulted in a
      significant increment in the gene expression of PPARdelta, a transcription factor
      clearly related with lipid catabolism in many tissues. Altogether, the results
      presented here suggest that IL-15 alters exogenous lipid partitioning, limiting
      adipose tissue uptake and favouring oxidation.

PMID- 16458592
TI  - Artifact reduction for EEG/fMRI recording: nonlinear reduction of
      ballistocardiogram artifacts.
AB  - OBJECTIVE: We present a new method of effectively removing the ballistocardiogram
      artifacts (BAs) of electroencephalography (EEG), recorded inside a 1.5 T static
      magnetic field scanner with no fMRI scanning, which conserves the time and
      frequency features of event-related EEG activity. METHODS: The BAs are
      approximated as deterministically chaotic dynamics. A Wavelet-based nonlinear
      noise reduction (WNNR) method consisting of: (a) wavelet transformation, (b)
      nonlinear noise reduction and (c) spatial average subtraction, is developed to
      effectively reduce the BAs so that the residual artifacts are smaller than the
      EEG signals. RESULTS: The effectiveness of the WNNR method to remove the BAs with
      conservation of the temporal EEG signals is evaluated by simulations and
      experiments inside a 1.5 T static magnetic field, with the visual evoked EEG
      dynamics. The WNNR method is also demonstrated to effectively retrieve alpha
      waves while the subjects' eyes are closed. CONCLUSIONS: The WNNR method has the
      abilities to effectively remove the BAs and conserve the time-frequency features
      of EEG activity. SIGNIFICANCE: The WNNR method provides us a significant
      technique to obtain clean temporal EEG signals during recording with MRI,
      especially for the event-related EEG dynamics. Notably, it might work effectively
      at higher field strengths as well. Moreover, it can be also used to process many
      other biological data contaminated by the cardiac pulses.

PMID- 16458593
TI  - Artifact reduction for simultaneous EEG/fMRI recording: adaptive FIR reduction of
      imaging artifacts.
AB  - OBJECTIVE: We present a new method of effectively removing imaging artifacts of
      electroencephalography (EEG) and extensively conserving the time-frequency
      features of EEG signals during simultaneous functional magnetic resonance imaging
      (fMRI) scanning under conventional conditions. METHODS: Under the conventional
      conditions of a 5000 Hz EEG sampling rate, but in the absence of the MRI slice
      timing signals, the imaging artifact during each slice scanning is theoretically
      inferred to be a linear combination of the average artifact waveform and its
      derivatives, deduced by band-limited Taylor's expansion. Technically, the imaging
      artifact reduction algorithm is equivalent to an adaptive finite impulse response
      (FIR) filter. RESULTS: The capability of this novel method removing the imaging
      artifacts of EEG recording during fMRI scanning has been demonstrated by a
      phantom experiment. Moreover, the effectiveness of this method in conserving the
      time-frequency features of EEG activity has been evaluated by both visually
      evoked experiments and alpha waves. CONCLUSIONS: The adaptive FIR method is an
      effective method of removing the imaging artifacts under conventional conditions,
      and also conserving the time-frequency EEG signals. SIGNIFICANCE: The proposed
      adaptive FIR method, removing the imaging artifacts, combined with the wavelet
      based non-linear noise reduction (WNNR) method [Wan X, Iwata K, Riera J, Ozaki T,
      Kitamura M, Kawashima R. Artifact reduction for EEG/fMRI recording: Nonlinear
      reduction of ballistocardiogram artifacts. Clin Neurophysiol 2006;117:668-80],
      reducing the ballistocardiogram artifacts (BAs), makes it feasible to obtain
      accurate EEG signals from the simultaneous EEG recordings during fMRI scanning.

PMID- 16458594
TI  - A system for automatic artifact removal in ictal scalp EEG based on independent
      component analysis and Bayesian classification.
AB  - OBJECTIVE: To devise an automated system to remove artifacts from ictal scalp
      EEG, using independent component analysis (ICA). METHODS: A Bayesian classifier
      was used to determine the probability that 2s epochs of seizure segments
      decomposed by ICA represented EEG activity, as opposed to artifact. The
      classifier was trained using numerous statistical, spectral, and spatial
      features. The system's performance was then assessed using separate validation
      data. RESULTS: The classifier identified epochs representing EEG activity in the
      validation dataset with a sensitivity of 82.4% and a specificity of 83.3%. An ICA
      component was considered to represent EEG activity if the sum of the
      probabilities that its epochs represented EEG exceeded a threshold predetermined
      using the training data. Otherwise, the component represented artifact. Using
      this threshold on the validation set, the identification of EEG components was
      performed with a sensitivity of 87.6% and a specificity of 70.2%. Most
      misclassified components were a mixture of EEG and artifactual activity.
      CONCLUSIONS: The automated system successfully rejected a good proportion of
      artifactual components extracted by ICA, while preserving almost all EEG
      components. The misclassification rate was comparable to the variability observed
      in human classification. SIGNIFICANCE: Current ICA methods of artifact removal
      require a tedious visual classification of the components. The proposed system
      automates this process and removes simultaneously multiple types of artifacts.

PMID- 16458595
TI  - Brain-computer-interface research: coming of age.

PMID- 16458596
TI  - The effects of auditory attention measured from human electrocorticograms.
AB  - OBJECTIVE: A central question in auditory electrophysiology has been whether
      selective attention can modulate exogenous components of the scalp-recorded N1
      (the 'N1 effect'). Intracranial electrocorticograms were used in the current work
      to investigate this issue in greater anatomical detail. METHODS: Data were
      recorded from subdural electrodes placed across temporal cortex in 6 patient
      volunteers undergoing diagnostic procedures for medically intractable epilepsy.
      Patients performed a dichotic listening task in which they alternately attended
      to a series of tones presented to both ears (mean ISI 800 ms) by responding to
      rare frequency deviants. RESULTS: Effects of attention were measured on the
      largest negative and positive waveform deflections observed between 70 and 220 ms
      post-stimulus for stimuli presented contralateral to grid location. Peak
      deflections were most often recorded from the upper bank of the posterior
      superior temporal gyrus at approximately 89 and 173 ms on average (labeled N90stg
      and P170stg, respectively). Selective attention had little effect on peak
      latencies but significantly increased the N90stg for 3 subjects, increased the
      P170stg for two subjects, and decreased the P170stg for two other subjects.
      CONCLUSIONS: Selective auditory attention can modulate neural response in
      auditory cortex. SIGNIFICANCE: The effects of attention on the scalp-recorded N1
      component may arise in part from the enhancement of exogenous responses in
      temporal cortex.

PMID- 16458597
TI  - Sleep with eyes wide open.

PMID- 16458598
TI  - Sleep effects of a 24-h versus a 16-h nicotine patch: a polysomnographic study
      during smoking cessation.
AB  - BACKGROUND AND PURPOSE: Sleep disturbance is a common symptom of tobacco
      withdrawal and might contribute to early relapse vulnerability in abstinent
      smokers. This study was designed to compare the effects on sleep of nicotine
      patches applied either for 24 h (Nicopatch) or 16 h (Nicorette). PATIENTS AND
      METHODS: During a short smoking cessation period (48 h), this open-label,
      randomised, two-period crossover study compared the effects on sleep of the two
      nicotine patches in 20 heavy smokers (9 women, 11 men). During each period,
      polysomnographic recordings were performed from 12 pm to 7 am for two consecutive
      nights (baseline and treatment nights). Smoking cessation started from 8 pm the
      day of the baseline sleep recordings, and treatments were applied around 8 am the
      following morning. RESULTS: Compared to the 16-h nicotine patch, smokers who
      received the 24-h nicotine patch experienced significantly less microarousals, a
      greater proportion of slow wave sleep, a higher REM density and higher rapid eye
      movement (REM) beta activities. CONCLUSIONS: The results of this study suggest
      that a 24-h nicotine patch is more efficient than a 16-h nicotine patch to
      alleviate tobacco withdrawal-induced sleep disturbances.

PMID- 16458599
TI  - Severe hypersomnolence associated with periodic limb movements and central sleep
      apnea in a cocaine addicted HIV patient.
AB  - Drugs such as cocaine and amphetamines potentiate the effect of epinephrine and
      norepinephrine on the brain and act as stimulants. Here, we report a case of
      paradoxical severe hypersomnolence from cocaine use in an HIV cocaine-addicted
      patient. We describe a possible pathomechanism for cocaine depletion at the
      synapse, causing decreased synaptic activation and leading to sleepiness.

PMID- 16458600
TI  - Floppy eyelid syndrome: clinical features and the association with obstructive
      sleep apnea.
AB  - Floppy eyelid syndrome (FES) is a recently recognized entity, originally
      described in obese men with easily everted upper eyelids and chronic ocular
      irritation. Although the eyelids are primarily involved, other ocular structures
      such as the conjunctiva and cornea are frequently affected and cause much of the
      morbidity. Recent studies have found an interesting association with obstructive
      sleep apnea (OSA) and with chronic diseases such as hypertension and diabetes.
      The association of FES with OSA has both diagnostic and therapeutic implications;
      FES may be a presenting symptom in patients with undiagnosed OSA, and, in
      addition, treatment of obesity and OSA may have a favorable effect on the course
      of FES.

PMID- 16458601
TI  - Effects of nicotine replacement therapies on sleep.

PMID- 16458602
TI  - Hyperthyroidism in a patient referred for an assessment of obstructive sleep
      apnea syndrome.

PMID- 16458604
TI  - Unraveling the relationship of obstructive sleep-disordered breathing to major
      depressive disorder.

PMID- 16458605
TI  - HIV-specific CD4+ T cells and viremia: who's in control?
AB  - It has been proposed that HIV-specific CD4+ T cells with a central memory
      phenotype might be involved in controlling HIV replication. Based on recent data
      (lack of protective effects of HIV-specific CD4+ T-cell responses in acutely
      infected patients undergoing treatment interruptions; loss of initially strong T
      helper cell responses in progressors to AIDS; and lack of prognostic value of HIV
      specific CD4+ T cells in a prospective study) we argue that the level of
      persistent viremia determines the fate of HIV-specific CD4+ T cells. We postulate
      that, rather than the absence of HIV-specific T cells, it is the viral and immune
      activation set points that are major determinants of progression to AIDS. This
      influences ideas about the type of cellular immunity a protective HIV vaccine
      should induce.

PMID- 16458606
TI  - Langerhans cells--revisiting the paradigm using genetically engineered mice.
AB  - Langerhans cells (LCs) are prominent dendritic cells (DCs) in epithelia, but
      their role in immunity and tolerance is poorly defined. 'Knockin' mice expressing
      enhanced green fluorescent protein (EGFP) under the control of the langerin
      (CD207) gene were recently developed in order to discriminate epidermal LCs from
      other DC subsets and at the same time to track their dynamics under steady-state
      or inflammatory conditions in vivo. Additional knockin mice expressing a
      diphtheria toxin receptor fused to EGFP were used to conditionally ablate LCs and
      assess their role in triggering hapten-specific T cell effectors through skin
      immunization. We review the insights that have been provided by these various
      knockin mice and discuss gaps in our knowledge of LCs that need to be filled.

PMID- 16458607
TI  - SHP2 forecast for the immune system: fog gradually clearing.
AB  - The src homology 2 (SH2) domain containing tyrosine phosphatase SHP2 (also
      referred to as SHP-2) is ubiquitously expressed in mammalian tissues and has been
      shown to be essential for embryonic development, haematopoiesis and signalling
      downstream of a variety of growth factors. Dysregulation of SHP2 function or
      expression has recently been implicated in the pathogenesis of human diseases
      involving haematopoietic cell lineages. New findings also demonstrate the
      involvement of SHP2 in the regulation of immune responses through its effects on
      cytokine and inhibitory receptor signalling pathways, and novel transgenic models
      are providing valuable insights into the role of SHP2 in T cells.

PMID- 16458609
TI  - Correlation between CD8+ T cells specific for prostate-specific antigen and level
      of disease in patients with prostate cancer.
AB  - Modest work has been performed to improve the sensitivity of residual disease
      detection or investigate the contribution that the immune system makes in
      controlling metastatic tumor growth, in particular, the frequency and biological
      actions of peptide-specific CD8+ T lymphocytes in limiting metastatic disease
      and/or maintaining remission. Fifty-three peripheral blood samples from 32
      prostate cancer (PC) patients were investigated for the presence of circulating
      prostate-specific antigen (PSA)-expressing cells (CPECs) using a highly sensitive
      and specific assay combining immunomagnetic epithelial cell enrichment with
      nested RT-PCR of PSA mRNA. Using HLA-A2 tetramer complexes, frequency of CD8+ T
      cells specific for PSA-derived peptides was determined. Additionally, serum
      concentrations of PSA and testosterone were measured. CPECs were detected in 26%
      of peripheral blood samples from PC patients. CD8+ T cells specific for PSA
      derived peptides were detected at low frequency in HLA-A2-positive PC patients.
      The correlation between these PSA-specific CD8+ T cells and residual prostate
      tumor cells and clinical measures was investigated. Our data suggest that
      frequency of PSA-specific CD8+ T cells is correlated to CPECs, but not to serum
      PSA level.

PMID- 16458610
TI  - Recommendations for chamber quantification.
AB  - Quantification of cardiac chamber size, ventricular mass and function ranks among
      the most clinically important and most frequently requested tasks of
      echocardiography. Over the last decades, echocardiographic methods and techniques
      have improved and expanded dramatically, due to the introduction of higher
      frequency transducers, harmonic imaging, fully digital machines, left-sided
      contrast agents, and other technological advancements. Furthermore,
      echocardiography due to its portability and versatility is now used in emergency
      rooms, operating rooms, and intensive care units. Standardization of measurements
      in echocardiography has been inconsistent and less successful, compared to other
      imaging techniques and consequently, echocardiographic measurements are sometimes
      perceived as less reliable. Therefore, the American Society of Echocardiography,
      working together with the European Association of Echocardiography, a branch of
      the European Society of Cardiology, has critically reviewed the literature and
      updated the recommendations for quantifying cardiac chambers using
      echocardiography. This document reviews the technical aspects on how to perform
      quantitative chamber measurements of morphology and function, which is a
      component of every complete echocardiographic examination.

PMID- 16458612
TI  - Metabolical changes induced by chronic phenol exposure in matrinxa Brycon
      cephalus (teleostei: characidae) juveniles.
AB  - Phenol and its derivatives are xenobiotics present in many industrial wastewaters
      and in non-specific pesticides. It is a lipophilic compound and, therefore,
      accumulates along the trophic chain. Phenol is often found in marine and fresh
      water environments. The aim of this work was to detect metabolic changes induced
      by phenol in Brycon cephalus juveniles. Several enzymes activities and
      metabolites were quantified in the liver, white muscle and plasma. Among the
      enzymes assayed are alanine and aspartate amino transferases (ALAT and ASAT),
      lactate dehydrogenase (LDH) and malate dehydrogenase (MDH). Glucose, glycogen,
      lactate, ammonia and pyruvate were also quantified in tissues and plasma
      (glycogen in tissues only). The liver was the most responsive organ. The
      activities of the transaminases increased in muscle and liver, followed by an
      increase in hepatic ammonia. Correlation between ammonia and transaminases points
      towards phenol-induced consumption of protein. Hepatic glycogen and glucose
      contents were lower followed exposure to phenol. The same was observed for muscle
      glucose, suggesting considerable use of carbohydrate stores. The activity of
      hepatic lactate dehydrogenase increased with negative correlation with muscle
      lactate. This suggests that hepatic gluconeogenesis supplies tissues like muscle
      and brain with glucose. These results indicate that phenol intoxication demands
      metabolic energy and leads to significant changes of the metabolic profile of the
      fish, inducing to a certain extent a shift from carbohydrate catabolism to
      protein catabolism and the activation of gluconeogenesis.

PMID- 16458611
TI  - Interaction between dietary calcium supplementation and chronic waterborne zinc
      exposure in juvenile rainbow trout, Oncorhynchus mykiss.
AB  - This study investigated the effects of dietary Ca2+ on branchial Ca2+ and Zn2+
      uptake, new and total zinc accumulation in target tissues (gill, liver and
      kidney), calcium and zinc homeostasis, and acute tolerance to waterborne zinc in
      fish chronically exposed to waterborne zinc. Juvenile rainbow trout (Oncorhynchus
      mykiss) were maintained on a calcium-enriched diet [41.2 mg vs. 21.2 mg (control)
      calcium/g dry wt. of food] and chronic waterborne zinc exposure (2.3 micromol/L),
      both separately and in combination, for 28 days. Calcium-supplemented diet in the
      absence of waterborne zinc significantly reduced branchial Ca2+ and Zn2+ influx
      rates, and new and total zinc accumulations in target tissues relative to
      control. However it did not protect against the acute zinc challenge. In
      contrast, waterborne zinc exposure significantly increased branchial Ca2+ and
      Zn2+ influx rates, new and total zinc concentrations in target tissues, and acute
      zinc tolerance relative to control. Interestingly, no such changes in any of
      these parameters were recorded in fish treated simultaneously with elevated
      dietary Ca2+ and waterborne zinc, except acute zinc tolerance which was highest
      among all the treatments. Thus, we conclude that the interactions between
      elevated dietary Ca2+ and waterborne zinc can protect freshwater fish against
      waterborne zinc toxicity.

PMID- 16458613
TI  - Cytotoxicity in the marine dinoflagellate Prorocentrum mexicanum from Brazil.
AB  - The microscopic algae in the oceans are crucial food for filter feeding bivalve
      shellfish (oysters, mussels, scallops, clams, etc.) as well as for the larvae of
      commercially important crustaceans. Some species of microalgae have the capacity
      to produce potent toxins, such as saxitoxins and ciguatoxins, which may
      intoxicate humans. Among the marine phytoplankton, the dinoflagellates are the
      main toxin producers. Studies on the marine phytoplankton from the Sao Sebastiao
      Channel, southeastern coast of Brazil, showed a great diversity of
      dinoflagellates. Some species were collected and cultured at the Marine Biology
      Center of the Sao Paulo University (USP). The polar (PEs) (aqueous) and apolar
      (AEs) (methylene chloride) extracts of the cultivated dinoflagellate species were
      tested on different stages of the sea urchin development, on mouse erythrocytes
      and on microfilaments organization in a neuroblastoma cell line. Prorocentrum
      mexicanum PE and AE induced cells anomalies and cell division inhibition of sea
      urchin eggs at EC50 of 78.75 microg/mL (95% CI from 32.56 to 190.50) and 22.50
      microg/mL (95% CI from 2.96 to 170.80) respectively (n=3). Both AE and PE of P.
      mexicanum induced hemolysis with EC50 of 65.07 microg/mL (95% CI from 27.40 to
      154.60) and 84.29 microg/mL (95% CI from 53.26 to 133.40 microg/mL),
      respectively. P. mexicanum PE was tested in immunofluorescence for actin
      filaments organization in neuroblastoma cultured cell.

PMID- 16458614
TI  - Notoginsenoside R1 from Panax notoginseng inhibits TNF-alpha-induced PAI-1
      production in human aortic smooth muscle cells.
AB  - Notoginsenoside R1 is the main ingredient with cardiovascular activity in Panax
      notoginseng. We reported that notoginsenoside R1 significantly decreased tumor
      necrosis factor-alpha (TNF-alpha)-induced plasminogen activator inhibitor-1 (PAI
      1) mRNA, protein level and secretion in human aortic smooth muscle cells (HASMCs)
      in a dose-dependent manner. TNF-alpha significantly increased extracellular
      signal-related kinases (ERK) and protein kinase B (PKB) activation and, which was
      blocked by notoginsenoside R1, PD098059, U0126 or wortmannin. Our data
      demonstrates that TNF-alpha-induced up-regulation of PAI-1 mRNA and protein
      levels and secretion occur via activation of ERK and PKB, which was prevented by
      treatment of notoginsenoside R1, PD098059, U0126 or wortmannin. These results
      suggest that notoginsenoside R1 inhibits TNF-alpha-induced PAI-1 overexpression
      in HASMCs by suppressing ERK and PKB signaling pathways.

PMID- 16458616
TI  - Influence of innocuous cervical vertebral movement on the efferent innervation of
      the adrenal gland in the rat.
AB  - In general, in central nervous system intact anesthetized animals, adrenal
      sympathetic efferent nerve activity and catecholamine secretion increase in
      response to noxious somatic stimulation, and decrease in response to innocuous
      somatic stimulation. In anesthetized rats, noxious chemical stimulation of the
      thoracic and lumbar interspinous tissues is associated with large increases in
      adrenal sympathetic efferent nerve activity and catecholamine secretion, with a
      clear segmental organization to the reflex apparent in spinalized animals.
      However, the adrenal sympathetic nerve responses to mechanical stimulation in the
      form of pressure applied laterally to the lower thoracic and lower lumbar
      vertebrae do not display segmental organization, and the depressor response is
      more characteristic of responses to innocuous somatic stimulation despite the use
      of large forces (up to 3.0 kg). Therefore, we sought to determine whether
      innocuous movements of the mechanoreceptor-rich deep tissues of the neck modulate
      the sympathetic outflow to the adrenal gland. We performed experiments in 14
      anaesthetised (Urethane 1 g/kg and Chloralose 0.1 g/kg) adult rats. Rats were
      intubated and breathed spontaneously. A computer driven small animal manipulator
      was used to impose ramp and hold rotational displacements (12 degrees /s, hold
      duration 2 s) of the 2nd cervical vertebra (range 2-30 degrees ) while recording
      multi-unit activity from sympathetic nerves innervating the adrenal gland. While
      noxious forepaw pinch elicited an increase in sympathetic nerve activity to the
      adrenal gland, there was no significant change in sympathetic nerve activity with
      small (2 degrees or 6 degrees ) rotations. Significant changes (P<0.05) in
      sympathetic activity were observed in only 7% (n=21) of all trials at larger
      displacements (12 degrees , 20 degrees , 25 degrees , 30 degrees n=287 trials).
      Our data suggest that although noxious stimuli may modulate sympathetic outflow,
      it is rare for afferents signalling innocuous cervical vertebral movements to
      modulate sympathetic nerves innervating the adrenal gland.

PMID- 16458615
TI  - Loss of parasympathetic innervation leads to sustained expression of pro
      inflammatory genes in the rat lacrimal gland.
AB  - It has been shown that removal of parasympathetic innervation to the lacrimal
      gland (LG) leads to rapid reduction in tear flow. Additionally, removal of the
      neural input resulted in disorganization of LG structure and changes in the
      expression of genes associated with the secretory pathway and inflammation. The
      goal of this study was to investigate the change in pro-inflammatory and pro
      apoptotic gene expression in the rat LG following parasympathetic denervation.
      Male Long-Evans rats underwent unilateral sectioning of the greater superficial
      petrosal nerve and were sacrificed 7 days or 2.5 months later. cDNA was
      synthesized from LG RNA from the contralateral control (Ctla) and
      parasympathectomized (Px) glands and comparative real-time PCR was performed.
      Mean threshold cycles (MC(T)) for the Ctla and Px LG genes were normalized to 18S
      rRNA MC(T) values, and the relative fold change was calculated for each gene
      using the 2(-DeltaDeltaC)(T) method. The expression of nuclear factor kappa B1,
      caspase 1, eotaxin, leukocyte antigen MRC-OX44, allograft inflammatory factor-1,
      MHC class II molecules RT.1B and RT.1D, IgG receptor FcRn, and macrophage
      metalloelastase was increased and remained elevated in the Px LG, compared with
      the Ctla LG. Increased expression of the initiator of apoptosis gene, caspase 2,
      was confirmed, but expression of the executor gene, caspase 6, was not elevated
      in the Px LG. Reduced expression of genes associated with post-translational
      protein processing-furin convertase, protein disulfide isomerase, and UDP-gal
      transporter isozyme 1-was noted in the Px LG. No significant changes in the
      expression of genes associated with lysosomal and non-lysosomal-mediated protein
      degradation were found. Removal of parasympathetic input may lead to decreased
      capacity for protein synthesis and elevated immune responses in the Px LG. These
      changes occur without increases in expression of the muscarinic acetylcholine
      receptor subtype 3, and may suggest the early changes in LG acinar cells and the
      pathophysiology of autoimmune responses.

PMID- 16458617
TI  - Has2 expression in heart forming regions is independent of BMP signaling.
AB  - Heart septation and valve malformations constitute the most common birth defects.
      These cardiac structures arise from the endocardial cushions through dynamic
      interactions between cells and the extracellular matrix (cardiac jelly). Targeted
      deletion of the hyaluronan synthase-2 (Has2) gene in mice results in an absence
      of cardiac jelly and endocardial cushions, a loss of vascular integrity, and
      embryonic death at E9.5. Despite the requirements for Has2 and its synthetic
      product hyaluronan (HA) in the developing cardiovascular system, little is known
      about the normal expression pattern of Has2 or the factors regulating Has2 gene
      transcription during development. Bmp signaling is an important regulator of
      cardiac myogenesis, and is also important for endocardial cushion formation. The
      current study defines the embryonic expression pattern of Has2 and explores the
      regulation of Has2 gene expression by Bmp signaling. In situ hybridization
      studies demonstrate dynamic Has2 expression patterns during myocardial cell
      development and cardiac tube formation, formation of the cardiac endocardial
      cushions, and cushion invasion by valve primordial cells. Despite overlapping
      regional expression of Bmp2 in the late gastrula anterior lateral endoderm and
      Has2 in the adjacent cardiogenic mesoderm, application of noggin-expressing CHO
      cells beneath the endoderm failed to perturb normal Has2 expression. Thus, in
      contrast to many genes expressed in the heart forming region, regulation of Has2
      in the cardiogenic mesoderm is independent of Bmp signaling.

PMID- 16458618
TI  - High pressure-low temperature processing of food proteins.
AB  - High pressure-low temperature (HP-LT) processing is of interest in the food field
      in view of: (i) obtaining a "cold" pasteurisation effect, the level of microbial
      inactivation being higher after pressurisation at low or sub-zero than at ambient
      temperature; (ii) limiting the negative impact of atmospheric pressure freezing
      on food structures. The specific effects of freezing by fast pressure release on
      the formation of ice I crystals have been investigated on oil in water emulsions
      stabilized by proteins, and protein gels, showing the formation of a high number
      of small ice nuclei compared to the long needle-shaped crystals obtained by
      conventional freezing at 0.1 MPa. It was therefore of interest to study the
      effects of HP-LT processing on unfolding or dissociation/aggregation phenomena in
      food proteins, in view of minimizing or controlling structural changes and
      aggregation reactions, and/or of improving protein functional properties. In the
      present studies, the effects of HP-LT have been investigated on protein models
      such as (i) beta-lactoglobulin, i.e., a whey protein with a well known 3-D
      structure, and (ii) casein micelles, i.e., the main milk protein components, the
      supramolecular structure of which is not fully elucidated. The effects of HP-LT
      processing was studied up to 300 MPa at low or sub-zero temperatures and after
      pressure release, or up to 200 MPa by UV spectroscopy under pressure, allowing to
      follow reversible structural changes. Pressurisation of approximately 2% beta
      lactoglobulin solutions up to 300 MPa at low/subzero temperatures minimizes
      aggregation reactions, as measured after pressure release. In parallel, such low
      temperature treatments enhanced the size reduction of casein micelles.

PMID- 16458619
TI  - Iron-sulfur cluster reconstitution of spinach chloroplast Rieske protein requires
      a partially prefolded apoprotein.
AB  - The Rieske 2Fe-2S protein is a central component of the photosynthetic electron
      transport cytochrome b6f complex in chloroplast and cyanobacterial thylakoid
      membranes. We have constructed plasmids for expression in Escherichia coli of
      full-length and truncated Spinacia oleracea Rieske (PetC) proteins fused to the
      MalE, maltose binding protein. The expressed Rieske fusion proteins were found
      predominantly in soluble form in the E. coli cytoplasm. These proteins could be
      readily purified for further experimentation. In vitro reconstitution of the
      characteristic, "Rieske-type" 2Fe-2S cluster into these fused proteins was
      accomplished by a chemical method employing reduced iron and sulfide. Cluster
      incorporation was monitored by electron paramagnetic resonance and optical
      circular dichroism (CD) spectroscopy. CD spectral analysis in the ultraviolet
      region suggests that the spinach Rieske apoprotein must be in a partially folded
      conformation to incorporate an appropriate iron-sulfur cluster. These data
      further suggest that upon cluster integration, further folding occurs, allowing
      the Rieske protein to attain a final, native structure. The data presented here
      are the first to demonstrate successful chemical reconstitution of the 2Fe-2S
      cluster into a Rieske apoprotein from higher plant chloroplasts.

PMID- 16458620
TI  - Eosinophilic oesophagitis as part of disseminated eosinophilic gastroenteritis?

PMID- 16458621
TI  - Long-term neurodevelopmental outcome of 167 children after intrauterine laser
      treatment for severe twin-twin transfusion syndrome.
AB  - OBJECTIVE: This study was undertaken to investigate long-term neurodevelopmental
      outcome of children born after intrauterine laser coagulation for severe twin
      twin transfusion syndrome. STUDY DESIGN: One hundred sixty-seven surviving
      infants treated between June 1997 and September 1999 were investigated at a
      median age of 3 years and 2 months. All children underwent a detailed
      standardized physical and neurologic examination and a standardized developmental
      test (Griffiths' Developmental Test Scales and Snijders-Oomen Non-Verbal
      Intelligence Test). RESULTS: One hundred forty-five infants (86.8%) showed normal
      development, 12 infants (7.2%) showed minor neurologic abnormalities, and 10
      infants (6.0%) major neurologic abnormalities. There was no difference in outcome
      for the former donors/recipients (P = .349) and between infants who were born as
      twins or singletons (P = .088). CONCLUSION: With a high rate (86.8%) of normal
      neurodevelopmental outcome and an incidence of only 6.0% of major neurologic
      deficiencies, intrauterine laser coagulation seems to be the best treatment
      option for severe twin-twin transfusion syndrome.

PMID- 16458622
TI  - A low vaginal "pool" amniotic fluid glucose measurement is a predictive but not a
      sensitive marker for infection in women with preterm premature rupture of
      membranes.
AB  - OBJECTIVE: We sought to identify the use of vaginal amniotic fluid (vAF) glucose
      measurements in predicting infection of the amniotic fluid retrieved by
      transabdominal amniocentesis (aAF) in women with preterm premature rupture of the
      membranes (PPROM). STUDY DESIGN: Fluid was retrieved by aAF was retreived from 35
      consecutive women with PPROM on whom an amniocentesis was clinically indicated to
      rule out intra-amniotic infection/inflammation and successfully completed. aAF
      was cultured for aerobic, anaerobic bacteria, Ureaplasma and Mycoplasma species.
      Clinical laboratory analysis for aAF included glucose concentration, Gram stain,
      lactate dehydrogenase, and white and red blood cell count. vAF was analyzed only
      for glucose concentration. Glucose concentration for the paired abdominal-vaginal
      AF samples (aAF-vAF) was determined by using well-established clinical and
      research laboratory methods. At the end of enrollment we stratified our patients
      into 2 groups: (1) positive microbial cultures (+)AFC (n = 17, gestational age
      [GA]: 27.3 +/- 0.7 weeks) or (2) negative microbial cultures (-)AFC (n = 18, GA:
      31.3 +/- 0.5 weeks). Cohen kappa measure of concordance and receiver operating
      characteristic (ROC) curve analysis were used to test the ability of the vaginal
      "pool" glucose measurements to discriminate between women with positive or
      negative AF cultures. RESULTS: Women with (+)AFC ruptured and delivered at an
      earlier GA compared with the (-)AFC group (p < .001). The latency period was
      similar (P = .35). There was a significant linear correlation between aAF and vAF
      glucose concentrations (r = 0.783, P < .001). Women with intra-amniotic infection
      (IAI) had significantly lower aAF [mean +/- SEM (+)AFC: 11.4 +/- 3.2 vs (-)AFC
      23.0 +/- 2.8 mg/dL, P = .01] and vAF glucose levels [(+)AFC: 10.1 +/- 2.8 vs (
      )AFC: 19.8 +/- 2.9 mg/dL, P = .02] compared with the noninfected group. Cohen
      kappa measure of concordance indicated "substantial" agreement between aAF and
      vAF glucose measurements (kappa = 0.719, 95% CI = 0.491-0.947). The sensitivity
      of the vAF glucose level to detect IAI ranged from 82% to 47%, whereas
      specificity ranged from 100% to 56% depending on the threshold we used. A vaginal
      "pool" (vAF) glucose measurement less than 5 mg/dL had 47.1% sensitivity, 100%
      specificity, 100% positive predictive value, 66.7% negative predictive value, and
      74.2% accuracy in identifying women with (+)AFC. CONCLUSION: Vaginal glucose
      determination is a readily available, inexpensive, rapid AF marker that can be
      measured practically in any clinical laboratory. vAF glucose measurements less
      than 5 mg/dL have predictive value, but low sensitivity for detection of IAI.

PMID- 16458623
TI  - Mapping the theories of preeclampsia: the need for systematic reviews of
      mechanisms of the disease.
AB  - Preeclampsia, a major cause of morbidity in pregnancy, is still a disease of
      unknown cause, despite considerable research in recent times. We believe that
      progress in understanding the disorder would be enhanced if the systematic review
      methodology, similar to that used to assess data from clinical trials, is applied
      to studies that investigate the many theories advanced to explain its cause. This
      article discusses the need for and a frame work of such an endeavor. The
      systematic review approach helps to determine where research should be focused,
      to prioritize the use of resources, to understand, and then hopefully to conquer
      a disease that still kills mothers and infants each year, worldwide.

PMID- 16458624
TI  - IVF results: optimize not maximize.
AB  - The desire to improve in vitro fertilization (IVF) results has led clinicians to
      replace more than 1 embryo in the uterus. As a result, multiple births have
      increased over the last 2 decades to epidemic proportions, exposing the field of
      assisted conception to justified criticism. This review aims to ensure that
      physicians involved in the field of fertility treatment are aware of the risks
      and complications related to multiple pregnancies, and to explore possible
      strategies such as blastocyst culture, preimplantation genetic screening, and
      embryo cryopreservation, which can help to control and reverse the tide of
      multiple pregnancies without reducing the good success rate that modern IVF
      treatment enjoys. A brief overview of the respective UK legislative system is
      also presented.

PMID- 16458625
TI  - Randomized trial of medical treatment versus hysterectomy for abnormal uterine
      bleeding: resource use in the Medicine or Surgery (Ms) trial.
AB  - OBJECTIVE: This study was undertaken to compare resource use outcomes for
      participants in the Medicine or Surgery (Ms) randomized trial. STUDY DESIGN: In a
      randomized controlled trial, we compared resources used during a 24-month follow
      up period by women with abnormal uterine bleeding who were randomly assigned to
      either expanded medical treatment or hysterectomy. RESULTS: Women randomly
      assigned to hysterectomy used significantly more resources (medicine = $4479,
      hysterectomy = $6777; P = .03), with almost all the difference caused by the
      hysterectomy procedure. Fifty-three percent of women randomly assigned to
      medicine had a hysterectomy during the follow-up period; women who were able to
      continue on medical therapy had mean total resource use of $2595 compared with
      $6128 for medicine patients who eventually had surgery. CONCLUSION: For women
      with abnormal uterine bleeding refractory to cyclic medroxyprogesterone acetate,
      compared with expanded medical treatment, hysterectomy increases resource use
      significantly and results in better clinical and 6-month quality-of-life
      outcomes.

PMID- 16458626
TI  - Risk factors for urinary incontinence among middle-aged women.
AB  - OBJECTIVE: The purpose of this study was to identify risk factors for urinary
      incontinence in middle-aged women. STUDY DESIGN: We conducted a cross-sectional
      analysis of 83,355 Nurses' Health Study II participants. Since 1989, women have
      provided health information on mailed questionnaires; in 2001, at the ages 37 to
      54 years, information on urinary incontinence was requested. We examined adjusted
      odds ratios of incontinence using logistic regression. RESULTS: Forty-three
      percent of the women reported incontinence. After adjustment, black (odds ratio,
      0.49; 95% CI, 0.40-0.60) and Asian-American women (odds ratio, 0.57; 95% CI, 0.46
      0.72) were at reduced odds of severe incontinence compared with white women.
      Increased age, body mass index, parity, current smoking, type 2 diabetes
      mellitus, and hysterectomy all were associated positively with incontinence.
      Women who were aged 50 to 54 years had 1.81 times the odds of severe incontinence
      compared with women who were <40 years old (95% CI, 1.66-1.97); women with a body
      mass index of > or =30 kg/m2 had 3.10 times the odds of severe incontinence
      compared with a body mass index of 22 to 24 kg/m2 (95% CI, 2.91-3.30).
      CONCLUSION: Urinary incontinence is highly prevalent among these middle-aged
      women. Potential risk factors include age, race/ethnicity, body mass index,
      parity, smoking, diabetes mellitus, and hysterectomy.

PMID- 16458627
TI  - An alpha-1 chain of type I collagen Sp1-binding site polymorphism in women
      suffering from stress urinary incontinence.
AB  - OBJECTIVE: We examined the possible influence of G-->T substitution in
      transcription factor Sp1-binding site in the gene encoding alpha-1 chain of type
      I collagen on the risk of stress urinary incontinence. STUDY DESIGN: The study
      group consisted of 50 women reporting symptoms of stress urinary incontinence.
      Fifty control subjects were treated for benign gynecological conditions other
      then stress urinary incontinence. DNA was obtained from peripheral blood
      leukocytes. The fragment of the first intron of the gene encoding the alpha-1
      chain of type I collagen containing the Sp1-binding site was amplified by
      polymerase chain reaction. The analysis of restriction fragment length
      polymorphism was performed. RESULTS: We found association between the GT and TT
      genotype and stress urinary incontinence (P = .019). The odds ratio for
      developing stress urinary incontinence is 4.98 (95% confidence interval 1.97 to
      12.56) in subjects presenting the GT genotype and 2.23 (95% confidence interval
      0.69 to 7.25) for the TT genotype. CONCLUSION: The G-T polymorphism at the Sp1
      binding site of the gene encoding alpha-1 chain of type 1 collagen is associated
      with increased risk of stress urinary incontinence in women.

PMID- 16458628
TI  - Value of laparoscopic assistance for vaginal hysterectomy with prophylactic
      bilateral oophorectomy.
AB  - OBJECTIVE: This study was undertaken to compare morbidity for women undergoing
      laparoscopy-assisted vaginal hysterectomy with bilateral oophorectomy (LAVHO) and
      vaginal hysterectomy with bilateral oophorectomy without laparoscopic assistance
      (VHO). STUDY DESIGN: Between April 1, 2002, and February 1, 2004, a prospective
      randomized study at Marseille University Hospital (La Conception) included 48
      patients who underwent a hysterectomy with prophylactic bilateral oophorectomy
      for benign uterine conditions. These patients were allocated to 2 groups (LAVHO
      vs VHO). The study variables were duration of surgery and of hospitalization and
      surgical and postoperative complications. RESULTS: There was no significant
      difference in the duration of surgery between the LAVHO and VHO groups (100.2 +/-
      27.9 vs 83.9 +/- 34.6, P = .08). The rate of complications was significantly
      higher in the LAVHO group (13/24 [54.1%] vs 6/24 [25%], P = .039). CONCLUSION:
      The overall complication rate was higher with LAVHO than VHO. It thus appears
      that laparoscopic assistance is not useful in performing vaginal hysterectomies
      with prophylactic bilateral oophorectomies in patients without other related
      disorders (endometriosis, adhesions, adnexal anomalies).

PMID- 16458629
TI  - Predictors of worsening insulin sensitivity in postmenopausal women.
AB  - OBJECTIVE: The purpose of this study was to determine predictors of worsening
      insulin sensitivity in postmenopausal women. STUDY DESIGN: Seventy-one nonobese
      postmenopausal women were assigned randomly to receive hormone replacement
      therapy (conjugated estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5
      mg) or placebo daily for 1 year (34 women received hormone replacement therapy,
      and 37 women received placebo). At baseline and 12 months, the women received a
      computed tomography scan at the L4-L5 vertebral disk space, a dual x-ray
      absorptiometry scan, a euglycemic hyperinsulinemic clamp to measure insulin
      sensitivity, and a lipid profile. Declining insulin sensitivity was defined as
      the largest quartile change in insulin sensitivity in the women who received the
      placebo (-1.42 mg/min/kg lean body mass). RESULTS: By univariate analysis, we
      found that significant predictors of worsening insulin sensitivity were the use
      of hormone replacement therapy, baseline insulin sensitivity, a younger age, and
      <10 years since menopause. By logistic regression, we determined that hormone
      replacement therapy use and higher baseline insulin sensitivity were independent
      predictors of worsening insulin sensitivity. CONCLUSION: The use of hormone
      replacement therapy and baseline insulin sensitivity are significant independent
      predictors of the development of worsening insulin sensitivity in postmenopausal
      women.

PMID- 16458630
TI  - Risks and usefulness of sonohysterography in patients with endometrial carcinoma.
AB  - OBJECTIVE: The purposes of this study were to assess the risk of malignant cell
      dissemination into the peritoneal cavity through the fallopian tubes in patients
      with endometrial carcinoma undergoing sonohysterography and to evaluate the
      accuracy of sonohysterography in the estimation of myometrial invasion by the
      tumor and its role in the preoperative staging. STUDY DESIGN: This was a
      prospective study that was conducted at the Sassari University hospital. Thirty
      two patients with endometrial carcinoma underwent sonohysterography during
      laparotomy for hysterectomy. The fluid that spilled from the fallopian tubes and
      was collected into graduated plastic tubes was analyzed by a pathologist. The
      presence of malignant endometrial cells in the fluid that was spilled from the
      fallopian tubes was assessed. The depth of myometrial invasion by tumor was
      assessed by gross and sonohysterographic examinations and compared with
      histopathologic findings. RESULTS: Malignant cells were reported in the fluid
      that spilled from the fallopian tubes in 2 patients (6.25%). The occurrence of
      suspected cells in the fallopian fluid was reported in 6 women (18.75%); thus,
      the presence of malignant or suspicious cells in the fluid that spilled from the
      fallopian tubes was reported in 8 of 32 cases (25%). Sonohysterography correctly
      evaluated the depth of myometrial invasion in 27 of 32 cases (84.37%).
      CONCLUSION: Sonohysterography was useful to assess the depth of myometrial
      invasion and may have a role in preoperative staging, but sonohysterography
      should not be performed in women with suspicious diagnosis of endometrial
      carcinoma.

PMID- 16458631
TI  - A prospective study of the effects of female and male marijuana use on in vitro
      fertilization (IVF) and gamete intrafallopian transfer (GIFT) outcomes.
AB  - OBJECTIVE: This study was undertaken to examine whether marijuana use affects in
      vitro fertilization and gamete intrafallopian transfer (IVF/GIFT). STUDY DESIGN:
      Prospective study of 221 IVF/GIFT couples. RESULTS: Amount of lifetime heavy
      marijuana use adversely affected IVF/GIFT. Women smoking more than 90 times in
      their lifetime had 27% fewer oocytes retrieved (P = .03) and 1 fewer embryo
      transferred (P < .05). Women smoking marijuana more than 10 times in their
      lifetime had infants 17% (P = .01) smaller at birth. If men smoked marijuana 11
      to 90 times in their lifetime, there was a 15% decrease in infant birth weight (P
      = .03); if this increased to more than 90 times, there was a 23% decrease (P =
      .01). Timing also played a role. Women smoking marijuana 1 year before IVF/GIFT
      had 25% fewer oocytes retrieved (P = .03), whereas couples had 28% (P = .04)
      fewer oocytes fertilized. Women and men who smoked in the past 15 years, had 12%
      (P = .04) and 16% (P = .03) smaller infants, respectively. CONCLUSION: Both
      timing and amount of marijuana use negatively affected IVF/GIFT.

PMID- 16458632
TI  - Preliminary results of 5% imiquimod cream in the primary treatment of vulva
      intraepithelial neoplasia grade 2/3.
AB  - OBJECTIVE: This study was undertaken to study the tolerability and efficacy of 5%
      imiquimod cream in the primary treatment of vulva intraepithelial neoplasia (VIN)
      grade 2/3. STUDY DESIGN: VIN grade 2/3 patients were recruited from regional
      colposcopy units. Imiquimod cream was applied over the abnormal area by the
      patient using an escalating dose regime for total treatment duration of 16 weeks.
      At the end of study, repeat colposcopy and biopsy of the target lesion were
      performed to assess for response. RESULTS: Twenty-three patients participated.
      Twenty patients (87%) had VIN grade 3. Nine patients (39%) had multifocal disease
      on colposcopy. Therapy was well tolerated with the most commonly observed side
      effects being irritation at the application site. Responses were evaluable in 17
      patients. Complete responses were observed in 9 patients with partial responses
      in another 5 (relative risk 82%). The median time to response was 7 weeks.
      CONCLUSION: Imiquimod cream can induce histologic regression of high-grade VIN
      lesions and is well tolerated using a slow dose-escalating regime.

PMID- 16458633
TI  - The association of psychosocial stress and bacterial vaginosis in a longitudinal
      cohort.
AB  - OBJECTIVE: The purpose of this study was to assess the association of
      psychosocial stress with bacterial vaginosis in a longitudinal sample of
      nonpregnant women. STUDY DESIGN: A 1-year prospective longitudinal design was
      used. Nonpregnant women (n = 3614) aged 15 to 44 years were recruited at routine
      health care visits. Assessments were conducted quarterly for 1 year and included
      a standardized pelvic examination, an assessment of clinical symptoms, and an
      extensive self-report interview. RESULTS: Psychosocial stress was associated with
      overall prevalence of (adjusted odds ratio, 1.10; 95% CI, 1.01-1.20) and an
      increased incidence of (adjusted odds ratio, 1.29; 95% CI, 1.12-1.48) bacterial
      vaginosis. The association between stress and bacterial vaginosis incidence was
      not changed appreciably by the control for behavioral and demographic
      characteristics and was magnified (odds ratio, 2.05; 95% CI, 1.15-3.66) in a case
      crossover analysis. CONCLUSION: Increased psychosocial stress is associated with
      greater bacterial vaginosis prevalence and incidence independent of other risk
      factors.

PMID- 16458634
TI  - Presence of HBsAg, HBcAg, and HBVDNA in ovary and ovum of the patients with
      chronic hepatitis B virus infection.
AB  - OBJECTIVE: The purpose of this study was to investigate the presence and
      distribution of Hepatitis B virus antigen (HBVAg) and Hepatitis B virus
      deoxyribonucleic acid (HBVDNA) in ovary with chronic hepatitis B virus. STUDY
      DESIGN: The immunohistochemistry method and in situ hybridization method were
      used to detect the hepatitis B surface antigen (HBsAg), anti-hepatitis B core
      antibody (HBcAg), and HBVDNA in ovary of patients with chronic hepatitis B
      infection. RESULTS: HBsAg presented in the ovum-granular cell and interstitial
      cell of ovary. HBsAg located in the cytomembrane and cytoplasm. HBcAg presented
      in the ovum-granular cell-interstitial cell and endothelium cell of interstitial
      blood vessel of ovary, and the HBcAg may present in the ovum at different stage.
      HBcAg was situated at the cytomembrane, cytoplasm, and nucleus. HBVDNA was
      detected in the ovum at different stage as HBcAg and in granular cell,
      interstitial cell of ovary. In the same ovary tissue, HBVDNA was positive in some
      ova, but it was weakly positive or negative in other ova. HBVDNA distributed
      mainly in nucleus, but also can be detected in the cytoplasm. CONCLUSION: HBV
      could infect the ovum at different stage and replicate in it. This may be an
      important mechanism of HBV vertical transmission.

PMID- 16458635
TI  - Screening for major structural abnormalities at the 11- to 14-week ultrasound
      scan.
AB  - OBJECTIVE: The purpose of this study was to examine the value of performing a
      detailed examination of the fetus as part of the routine 11 to 14 weeks'
      ultrasound scan in a 2-stage screening process for major structural defects in
      low-risk pregnancies. STUDY DESIGN: This was a prospective study in 1148
      singleton pregnancies at 11 to 14 weeks of gestation using a combination of
      transabdominal and transvaginal sonography to estimate the sensitivity of the
      first and second trimester ultrasound scan in the detection of major anomalies.
      RESULTS: Seven of the 14 major anomalies were detected at the 11 to 14 weeks
      scan, and an additional 6 at the second trimester scan. The sensitivity of the
      early anatomic examination and the overall sensitivity of the 2-stage screening
      were 50% and 92.8%, respectively. Nuchal translucency was increased in 5 of the
      14 (35.7%) abnormal fetuses and in 1 of the 4 cases (25%) with major heart
      defects. CONCLUSION: Detailed, structured examination of fetal anatomy during the
      routine 11 to 14 weeks' scan can detect half of major structural defects in low
      risk pregnancies.

PMID- 16458636
TI  - Sonographic screening for trisomy 13 at 11 to 13(+6) weeks of gestation.
AB  - OBJECTIVE: The purpose of this study was to examine the sonographic features of
      trisomy 13 at 11 to 13(+6) weeks of gestation. STUDY DESIGN: This was a
      retrospective study that examined the features of trisomy 13 at the ultrasound
      scan at 11 to 13(+6) weeks of gestation, which in our center is performed for the
      measurement of crown-rump length, nuchal translucency thickness, and fetal heart
      rate and the examination for major defects. RESULTS: In the 181 fetuses with
      trisomy 13, there were holoprosencephaly, exomphalos, and/or megacystis in 92
      fetuses (50.2%), fetal heart rate above the 95th percentile in 129 fetuses
      (71.3%), and nuchal translucency above the 95th percentile in 141 fetuses
      (77.9%). There was no significant association between nuchal translucency and
      fetal heart rate, and it was estimated that inclusion of fetal heart rate in
      nuchal translucency screening can improve the detection rate of trisomy 13 by
      approximately 5%. CONCLUSION: At the 11 to 13(+6)-week scan, the measurement of
      fetal nuchal translucency and fetal heart rate and fetal examination for
      holoprosencephaly, exomphalos, and megacystis can identify >90% of fetuses with
      trisomy 13.

PMID- 16458637
TI  - Quality of obstetric care and risk-adjusted primary cesarean delivery rates.
AB  - OBJECTIVE: The purpose of this study was to examine the association between risk
      adjusted primary cesarean delivery rates and maternal and neonatal outcomes.
      STUDY DESIGN: California birth certificate data that were linked to hospital
      discharge data for 2001 were used to create a primary cesarean delivery rate risk
      adjustment model. Two hundred eighty-five hospitals were divided into 3 groups
      that were above, below, or within expected rate confidence intervals. Maternal
      and neonatal outcomes were compared within each of the 3 hospital groupings.
      RESULTS: Of the 285 hospitals, 27% had primary cesarean delivery rates that were
      above expected confidence intervals; 34% had primary cesarean delivery rates that
      were below expected confidence intervals, and 39% had primary cesarean delivery
      rates that were within expected confidence intervals. Neonatal asphyxia rates
      were higher in hospitals that had lower than expected rates of cesarean
      deliveries (0.05%, 0.1%, 0.07% for above, below, and within the confidence
      intervals, respectively; P < .0001). Maternal infection rates (2.1%, 2.3%, 1.8%,
      respectively; P < .0001) and third-degree tears (2.3%, 3.0%, 2.6%, respectively;
      P < .0001) were also higher in hospitals for which the cesarean delivery rates
      were above or below the expected rates. CONCLUSION: Risk-adjusted primary
      cesarean delivery rates are a good marker for maternal and neonatal outcomes.

PMID- 16458638
TI  - Targeted prenatal herpes simplex virus testing: can we identify women at risk of
      transmission to the neonate?
AB  - OBJECTIVE: Potential strategies to prevent neonatal herpes include herpes simplex
      virus (HSV) serologic testing and counseling of pregnant women and rapid HSV
      polymerase chain reaction (PCR) testing of maternal genital secretions at
      delivery. The cost-effectiveness of these interventions would be improved if high
      risk pregnancies could be easily identified for targeted testing. STUDY DESIGN:
      Washington State birth certificate data for all singleton live births from 1987
      through 2002 were linked with infant death and hospital discharge data for birth
      and subsequent hospitalizations in a population-based case-control study of risk
      factors for neonatal herpes. A case was defined as an infant with a discharge
      diagnosis of HSV infection (International Classification of Diseases 9th edition
      [ICD-9] code 054.X) from birth admission or readmission within 30 days of life.
      Five controls per case were frequency matched to cases by year of birth. RESULTS:
      Ninety-one neonatal HSV cases were identified (8.4/100,000 live births). Risk
      factors for infection included maternal age younger than 25 years (adjusted odds
      ratio [aOR] = 1.9, 95% CI 1.1-3.3) and paternal age younger than 20 years or
      unknown (aOR = 1.7, 95% CI 0.7-3.7). Testing couples with either risk factor
      would require testing 36% of couples and could potentially prevent up to 60% of
      cases. Maternal history of genital herpes, fever during labor, and premature
      rupture of membranes were also associated with neonatal disease; using all risk
      factors identifiable at delivery would require screening 60% of pregnancies and
      identifying 84% of cases. CONCLUSION: Targeted HSV testing would miss a
      substantial proportion of neonatal herpes.

PMID- 16458640
TI  - Cervical preparation using laminaria with adjunctive buccal misoprostol before
      second-trimester dilation and evacuation procedures: a randomized clinical trial.
AB  - OBJECTIVE: This study was undertaken to determine whether buccal misoprostol
      improves cervical preparation achieved with laminaria before second-trimester
      dilation and evacuation procedures. STUDY DESIGN: A randomized, double blind,
      placebo-controlled trial of preoperative cervical preparation with overnight
      laminaria and either buccal placebo or 400 microg buccal misoprostol
      approximately 90 minutes before second-trimester surgical abortion. Block
      randomization was used to provide balanced enrollment into 2 separate gestational
      age study groups: early (13-15(6/7)) and mid (16-20(6/7)) second trimester.
      Surgeons tested maximal cervical dilation by inserting the largest dilator that
      could be passed through the cervical os without force. Subject demographics and
      preprocedure symptoms were tracked. RESULTS: Groups were similar in regard to
      age, gravity, parity, delivery type, and gestational age. Data were analyzed from
      125 women in the 13 to 15(6/7) (30 misoprostol, 32 placebo) and 16 to 20(6/7) (31
      misoprostol, 32 placebo) gestational age groups. Overall, misoprostol treatment
      did not improve the initial mean dilation achieved with laminaria alone in either
      the 13 to 15(6/7) (46.0 fr +/- 5.0; placebo 45.0 fr +/- 6.2, P = .68) or 16 to
      20(6/7) (50.9 fr +/- 5.6, placebo 48.9 fr +/- 5.2, P = .16) groups. However, a
      subanalysis of gestations 19 weeks or more demonstrated significantly greater
      dilation in the misoprostol group (53.6 fr fr +/- 5.3, placebo 48.5 fr +/- 5.0, P
      = .01). Subjects receiving misoprostol reported significantly more cramping than
      those receiving placebo (13-15(6/7) weeks misoprostol 25/30, 83%; placebo 17/32,
      53%, P = .02; 16-20(6/7) week misoprostol 25/31, 81%, placebo 16/32, 50%, P =
      .02). CONCLUSION: Cervical dilation with laminaria is augmented by 400 microg
      buccal misoprostol in gestations 19 weeks or more, but not in earlier gestations.
      Misoprostol causes more abdominal cramping.

PMID- 16458639
TI  - Comparative study of perinatal outcome of dichorionic and trichorionic iatrogenic
      triplets.
AB  - OBJECTIVE: The purpose of this study was to compare the perinatal outcome of
      dichorionic and trichorionic triplets who were conceived by assisted reproductive
      techniques. STUDY DESIGN: In this retrospective study, the maternal, neonatal,
      and chorionicity data were collected from 106 sets of trichorionic triamniotic
      and 34 sets of dichorionic triamniotic triplet pregnancies who were conceived by
      assisted reproductive techniques between January 1986 and December 2000.
      Perinatal and neonatal data were evaluated in relation to chorionicity and
      intertriplet birth weight discordance. RESULTS: The dichorionic triamniotic
      triplets have an 8-fold higher risk of perinatal death than trichorionic
      triamniotic gestations (odds ratio, 7.9; 95% CI, 4.4-14.0; P < .001). This is
      attributed to a higher risk of very low birth weight (P < .01), delivery at < 30
      weeks of gestation (P < .001), and premature rupture of membrane (P < .001) in
      dichorionic triamniotic triplets compared with trichorionic triamniotic
      pregnancies. Twin-twin transfusion syndrome (odds ratio, 11.5; 95% CI, 4.8-27.7;
      P < .001), delivery at < 30 weeks of gestation (odds ratio, 40.5; 95% CI, 16.9
      97; P < .01), premature rupture of membrane (odds ratio, 6.7; 95% CI, 3.8-11.9; P
      < .01), and nulliparity (odds ratio, 3.1; 95% CI, 1.6-6.1; P < .05) had
      independent effects on perinatal loss rate. CONCLUSION: The dichorionic triplets
      have an 8 times higher perinatal mortality rate than trichorionic triamniotic
      pregnancies.

PMID- 16458641
TI  - Pregnancy outcome of patients with gestational diabetes mellitus following
      bariatric surgery.
AB  - OBJECTIVE: The objective of the study was to investigate pregnancy outcome of
      patients with gestational diabetes mellitus following bariatric surgery. STUDY
      DESIGN: All births to patients with gestational diabetes mellitus delivered
      between the years 1988 and 2002 were included in the study. A comparison between
      patients with and without a history of bariatric surgery was performed.
      Stratified analyses, using the Mantel-Haenszel technique and a multiple logistic
      regression model were performed to control for confounders. RESULTS: During the
      study period, there were 8014 deliveries of women with gestational diabetes
      mellitus. Twenty-eight were in patients following bariatric surgery. Most
      patients underwent restrictive (n = 26) and not malabsorptive procedures (n = 2),
      mainly gastric banding (n = 16). Mean levels of hemoglobin A1c and fasting
      glucose were comparable between the groups. No significant differences in
      obstetric characteristics or pregnancy outcomes were noted between the patients
      following bariatric surgery as compared with the comparison group, except for
      higher rates of fertility treatments (21.4% versus 5.5%; P < .001). While
      controlling for nulliparity and maternal age, using a multivariable analysis, a
      significant association was noted between bariatric surgery and fertility
      treatments (odds ratios 4.7; 95% confidence interval 1.9 to 11.7; P = .001).
      Perinatal outcome was comparable between the groups, and no significant
      differences were noted with regard to complications such as perinatal mortality,
      congenital malformations, and low Apgar scores at 1 and 5 minutes. CONCLUSION:
      Previous bariatric surgery in patients with gestational diabetes mellitus is not
      associated with adverse perinatal outcome.

PMID- 16458642
TI  - Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis
      after cesarean section.
AB  - In the run-in phase of a thromboprophylactic trial in women at moderate to high
      risk of deep vein thrombosis postcesarean section, we used magnetic resonance
      venography and found a surprisingly high rate of pelvic deep vein thrombosis (46%
      overall). Pelvic magnetic resonance venography may be a useful surrogate outcome
      in obstetric thromboprophylaxis studies but the clinical significance is not
      known.

PMID- 16458643
TI  - The NICHD-MFMU antibiotic treatment of preterm PROM study: impact of initial
      amniotic fluid volume on pregnancy outcome.
AB  - OBJECTIVE: The purpose of this study was to evaluate the associations between
      measured amniotic fluid volume and outcome after preterm premature rupture of
      membranes (PROM). STUDY DESIGN: This was a secondary analysis of 290 women, with
      singleton pregnancies, who participated in a trial of antibiotic therapy for
      preterm PROM at 24(0) to 32(0) weeks. Each underwent assessment of the 4 quadrant
      amniotic fluid index (AFI) and a maximum vertical fluid pocket (MVP) before
      randomization. The impact of low AFI (< 5.0 cm) and low MVP (< 2.0 cm) on
      latency, amnionitis, neonatal morbidity, and composite morbidity (any of death,
      RDS, early sepsis, stage 2-3 necrotizing enterocolitis, and/or grade 3-4
      intraventricular hemorrhage) was assessed. Logistic regression controlled for
      confounding factors including gestational age at randomization, GBS carriage, and
      antibiotic study group. RESULTS: Low AFI and low MVP were identified in 67.2% and
      46.9% of women, respectively. Delivery occurred by 48 hours, 1 and 2 weeks in
      32.4%, 63.5% and 81.7% of pregnancies, respectively. Both low AFI and low MVP
      were associated with shorter latency (P < .001), and with a higher rate of
      delivery at 48 hours, 1, and 2 weeks (P = .02 for each). However, neither test
      offered significant additional predictive value over the risk in the total
      population. Low AFI and low MVP were not associated with increased amnionitis.
      After controlling for other factors, both low MVP and low AFI were associated
      with shorter latency (P < or = .002), increased composite morbidity (P = .03),
      and increased RDS (P < or = .01), but not with increased neonatal sepsis (P =
      .85) or pneumonia (P = .53). Alternatively, after controlling for fluid volume,
      gestational age, and GBS carriage, the antibiotic study group had longer latency,
      and suffered less common primary outcomes and neonatal sepsis. CONCLUSION:
      Oligohydramnios should not be a consideration in determining which women will be
      candidates for expectant management or antibiotic treatment when it is identified
      at initial assessment of preterm PROM remote from term.

PMID- 16458644
TI  - Sulprostone reduces the need for the manual removal of the placenta in patients
      with retained placenta: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to determine the extent that the
      administration of sulprostone reduces the need for manual removal of the placenta
      in patients with retained placenta. STUDY DESIGN: A double-blinded sequential
      randomized controlled trial of sulprostone versus placebo was conducted among 103
      patients with retained placenta. RESULTS: In the first phase of this sequential
      study, sulprostone was compared with placebo. The null hypothesis of equal
      effectiveness of both treatments was rejected after 50 patients. In patients with
      retained placenta, the placenta was expelled after sulprostone in 13 of 24 cases
      (51.8%, bias adjusted), whereas expulsion after placebo was achieved in only 4 of
      26 cases (17.6%, bias adjusted). The difference was significant (P = .034). In
      the second phase of the study, in which the placebo arm was stopped, results were
      confirmed; in 25 of 53 patients (47%), the placenta was expelled. CONCLUSION:
      Sulprostone reduces the need for the manual removal of the placenta by 49%.

PMID- 16458645
TI  - Tuberculosis prevention for non-US-born pregnant women.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether non-US-born pregnant
      women receiving prenatal care are targeted for treatment of latent tuberculosis
      (TB) infection (LTBI) with isoniazid (INH) to prevent active TB. STUDY DESIGN:
      This was a retrospective chart review study of 730 non-US-born pregnant women
      receiving care at 5 New York City prenatal clinics from 1999 to 2000. RESULTS:
      Among 678 women with known tuberculin skin test (TST) status, 341 (50.3%) had a
      TST-positive result, including 200 who were newly diagnosed. Of 291 TST-positive
      women with no previous LTBI treatment or history of TB, 27 (9.3%) completed > or
      =6 months of INH. In a subset with detailed follow-up, the most important reasons
      for not completing treatment were nonreferral for evaluation of a TST-positive
      result (30.9%), not keeping the appointment (17.9%), and nonadherence with
      prescribed treatment (34.6%). CONCLUSION: The prenatal setting represents a
      missed opportunity to link TST-positive non-US-born women with LTBI treatment and
      support for treatment completion.

PMID- 16458646
TI  - Impaired factor XIIa-dependent activation of fibrinolysis in treated
      antiphospholipid syndrome gestations developing late-pregnancy complications.
AB  - OBJECTIVE: The objective of the study was to investigate the potential role of
      impaired factor XII-dependent activation of fibrinolysis in treated
      antiphospholipid syndrome gestations developing late-pregnancy complications.
      STUDY DESIGN: This was a prospective study in a third-level teaching hospital,
      including 75 patients: 25 pregnant patients having the antiphospholipid syndrome
      and carrying their pregnancies until 26 weeks' gestation or later (group 1); 25
      pregnant patients having normal term pregnancies and delivery and no previous
      miscarriage (group 2); and 25 pregnant patients being diagnosed as having severe
      pre-eclampsia and/or intrauterine growth restriction but testing negative for
      antiphospholipid antibodies (group 3). Hemostatic evaluation was carried out from
      patients in groups 1 and 2 between 6 and 10 weeks, between 18 and 22 weeks, and
      between 28 and 32 weeks' gestation. Patients in group 3 were sampled between 28
      and 32 weeks. An additional blood sample was obtained 4 to 6 months after
      delivery (baseline). The Mann-Whitney U test, the Friedman test, and the chi2
      test were used. RESULTS: Patients in group 1 were characterized by increased
      factor VIIa levels, increased prothrombin fragment 1+2 levels, reduced factor
      XIIa levels, diminished functional urokinase-type plasminogen activator levels,
      and decreased levels of plasmin/alpha-2-plasmin inhibitor complexes. These
      abnormalities were more evident in patients in group 1 developing pre-eclampsia
      and/or intrauterine growth restriction. CONCLUSIONS: Impaired factor XIIa
      dependent activation of fibrinolysis seems to be a key mechanism related to late
      pregnancy complications in patients with the antiphospholipid syndrome.

PMID- 16458647
TI  - Optimal timing of ampicillin administration to pregnant women for establishing
      bactericidal levels in the prophylaxis of Group B Streptococcus.
AB  - OBJECTIVE: The purpose of this study was to determine the time necessary to
      achieve and maintain bactericidal concentrations of ampicillin in the cord blood.
      STUDY DESIGN: This was a prospective study in which women scheduled for an
      elective cesarean section were given intravenous ampicillin before the procedure.
      Cord and simultaneous maternal blood samples were collected at the time of
      delivery. Serum ampicillin levels were analyzed by high-performance liquid
      chromatography. RESULTS: The ratio of cord blood to maternal serum ampicillin
      concentration was found to increase over time in a linear fashion. There was no
      correlation between maternal body mass index (22.3 to 48.3 kg/m2) and ampicillin
      cord blood concentrations. All cord serum samples far exceeded minimal
      bactericidal concentrations reported for Group B Streptococcus (0.25 to 2.0
      microg/mL), even at 338 minutes following administration. CONCLUSION:
      Bactericidal levels of ampicillin in the cord blood are rapidly achieved within
      30 minutes of administration of ampicillin to the mother. The increase in the
      ratio of cord to maternal serum ampicillin levels is directly related to time,
      suggesting a decrease in the clearance of ampicillin in the newborns as compared
      to the mothers. The cord blood ampicillin concentration exceeds the maternal
      concentration and both continue to be above the minimal bactericidal
      concentrations at 5.6 hours after administration. No relationship was observed
      between the maternal body mass index and ratio of cord to maternal serum
      concentrations of ampicillin.

PMID- 16458648
TI  - Screening for thyroid disorders during pregnancy: results of a survey in Maine.
AB  - OBJECTIVE: Guidelines regarding prenatal screening for thyroid deficiency are
      conflicting, and current practice in primary care settings is unknown. Our survey
      sought to determine the: 1) extent of screening in Maine; 2) factors associated
      with screening; and 3) laboratory cut-off levels used. STUDY DESIGN: In 2004 we
      surveyed 61 prenatal care practices, representing 246 practitioners and 85% of
      Maine deliveries. RESULTS: Screening via thyroid-stimulating hormone (TSH)
      testing was routine in 48% of the practices. Obstetrician practices screened at a
      significantly higher rate than family practices (56% vs 8%; odds ratio [OR] 15.0,
      95% CI 1.9-130.0). Nonsignificant higher rates were found for urban versus rural,
      and multipractitioner versus solo practices. The lower TSH cut-off levels ranged
      between 0.1 and 0.5 mU/L among practices; the upper cut-off levels ranged between
      3.5 and 5.5 mU/L. CONCLUSION: Prenatal screening for thyroid deficiency varies
      among practices, reflecting conflicting guidelines. TSH cut-offs are also
      variable and might benefit from standardization.

PMID- 16458649
TI  - Familial aggregation of small-for-gestational-age births: the importance of fetal
      genetic effects.
AB  - OBJECTIVE: This study was undertaken to disentangle the maternal genetic, fetal
      genetic, and environmental effects for the risk of having small-for-gestational
      age (SGA) offspring. STUDY DESIGN: By cross-linking the population-based Swedish
      Multi-Generation and Medical Birth Registers, we extracted 2,193,142 births
      between 1973 and 2001 with both parents identified. Odds ratios (OR) were
      calculated to estimate the relative risks, and generalized linear mixed models
      were used to estimate the contribution of genetic and environmental effects.
      RESULTS: Women whose full sisters had an offspring born SGA had a significantly
      increased risk of having a SGA offspring themselves (OR = 1.8, 95% CI 1.7-1.9),
      whereas the corresponding risk for brothers was lower (OR = 1.3, 95% CI 1.2-1.4).
      Thirty-seven percent of the liability was explained by fetal (including both
      maternal and paternal) genetic effects and 9% by maternal genetic effects.
      CONCLUSION: Genetic factors account for almost half of the liability to have SGA
      births. These effects are primarily caused by fetal genes.

PMID- 16458650
TI  - Use of oral decongestants during pregnancy and delivery outcome.
AB  - OBJECTIVE: The purpose of this study was to evaluate delivery outcome after
      maternal use of oral decongestants. STUDY DESIGN: We identified 2474 women who
      had reported the use of oral decongestants (mainly phenylpropanolamine) during
      early pregnancy and 1771 women who used prescription oral decongestants later in
      pregnancy. With Mantel-Haenszel analysis, comparisons were made with all women
      who gave birth in Sweden. RESULTS: The risk ratio for any congenital malformation
      after the use of oral decongestants was 0.96 (95% CI, 0.80-1.16). Women who were
      prescribed decongestants after the first antenatal visit less often than expected
      had infants who were born preterm (odds ratio, 0.68; 95% CI, 0.52-0.88), of low
      birth weight (odds ratio, 0.53; 95% CI, 0.37-0.77), small-for-date (odds ratio,
      0.71; 95% CI, 0.47-1.08), or perinatally dead (odds ratio, 0.53; 95% CI, 0.22
      12.5). CONCLUSION: No teratogenic effect of oral decongestants was found. An
      association found between the late pregnancy use of such drugs and a favorable
      neonatal outcome can be explained hypothetically by the postulated association
      between pregnancy rhinitis and placental hormones.

PMID- 16458651
TI  - Risk factors for brachial plexus injury with and without shoulder dystocia.
AB  - OBJECTIVE: To ascertain whether brachial plexus palsy (BPP) that occurs without
      shoulder dystocia (SD) represents a traction injury during unrecognized SD or a
      natural phenomenon with a different mechanism of injury, we compared risk factors
      and outcomes between SD-associated and non-SD-associated BPP. STUDY DESIGN:
      Neonates with BPP after cephalic vaginal delivery were pooled from all deliveries
      at Johns Hopkins (June, 1993-December, 2004) and a dataset of litigated permanent
      BPP from multiple institutions (1986-2003), grouped by SD association based on
      clinician documentation and compared by using Fisher exact and t tests. RESULTS:
      Thirty percent of 49 non-SD-BPP and 11% of 280 SD-BPP lacked all risk factors for
      SD (P = .002). Compared with SD-BPP infants, non-SD-BPP infants were average
      weight (P < .001) and had cord pH less than 7.10 (P = .01) more commonly and
      exhibited a trend toward posterior shoulder involvement (P = .06). Nearly all non
      SD-BPP were temporary, whereas more than 90% of permanent BPP were associated
      with SD (odds ratio 17, 7.3-39.6). CONCLUSION: Non-SD-BPP is uncommon and likely
      mechanistically distinct from SD-BPP. Risk factors, birth weight, fetal acidosis,
      posterior arm involvement, and injury severity distinguish between shoulder
      dystocia-related brachial plexus injuries and those not recorded as such.

PMID- 16458653
TI  - What proportion of birth weight is attributable to maternal glucose among infants
      of diabetic women?
AB  - OBJECTIVE: This study was undertaken to determine the proportion of birth weight
      attributable to glucose concentrations of diabetic mothers. STUDY DESIGN: Data of
      diabetic women who used insulin were eligible for analysis if the women had been
      treated during pregnancy for at least 12 weeks, and had recorded at least 50% of
      4 daily glucose checks (fasting and 1-hour postprandial) until the last office
      visit before delivery. The independent association between maternal glucose
      values and demographics and birth weight percentiles for gestational age and
      gender were analyzed by multiple regression methods. RESULTS: Data of 90 diabetic
      women were analyzed. Only third-trimester glucose concentrations were associated
      with birth weight. Prepregnancy body mass index was also selected in the models,
      including second- and/or third-trimester glucose. Together, these variables
      explained 18% of the variance in birth weight percentiles. CONCLUSION: Maternal
      glycemia during third-trimester and prepregnancy body mass index are independent
      predictors of birth weight in pregnancies complicated by insulin-requiring
      gestational or type 2 diabetes.

PMID- 16458652
TI  - Midpregnancy genitourinary tract infection with Chlamydia trachomatis:
      association with subsequent preterm delivery in women with bacterial vaginosis
      and Trichomonas vaginalis.
AB  - OBJECTIVE: The objective of the study was to estimate whether midpregnancy
      genitourinary tract infection with Chlamydia trachomatis is associated with an
      increased risk of subsequent preterm delivery. STUDY DESIGN: Infection with C.
      trachomatis was determined using a ligase chain reaction assay (performed in
      batch after delivery) of voided urine samples collected at the randomization
      visit (16(0/7) to 23(6/7) weeks' gestation) and the follow-up visit (24(0/7) to
      29(6/7) weeks) among 2470 gravide women with bacterial vaginosis or Trichomonas
      vaginalis infection enrolled in 2 multicenter randomized antibiotic treatment
      trials (metronidazole versus. placebo). RESULTS: The overall prevalence of
      genitourinary tract C. trachomatis infection at both visits was 10%. Preterm
      delivery less than 37 weeks' or less than 35 weeks' gestational age was not
      associated with the presence or absence of C. trachomatis infection at either the
      randomization (less than 37 weeks: 14% versus 13%, P=.58; less than 35 weeks:
      6.4% versus 5.5%, P=.55) or the follow-up visit (less than 37 weeks: 13% versus
      11%, P=.33; less than 35 weeks: 4.4% versus 3.7, P=.62). Treatment with an
      antibiotic effective against chlamydia infection was not associated with a
      statistically significant difference in preterm delivery. CONCLUSION: In this
      secondary analysis, midtrimester chlamydia infection was not associated with an
      increased risk of preterm birth. Treatment of chlamydia was not associated with a
      decreased frequency of preterm birth.

PMID- 16458654
TI  - Prospective study of 22q11 deletion analysis in fetuses with excess nuchal
      translucency.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency of 22q11
      deletions (DiGeorge, velocardiofacial syndromes) in chromosomally normal fetuses
      with excess nuchal translucency. STUDY DESIGN: We evaluated chorionic villus
      sampling (CVS) samples submitted with an indication of excess nuchal
      translucency. If chromosome analysis was normal, permission was obtained to
      perform 22q11 microdeletion fluorescence in situ hybridization analysis. By
      Fisher exact test, the null hypothesis that there is no association between
      excess nuchal translucency and 22q11 deletions was tested. RESULTS: Among 239 CVS
      samples from fetuses with excess nuchal translucency, 93 (39%) were chromosomally
      abnormal. Of the remaining 146 specimens, 80 CVS samples were chromosomally
      normal, had documentation of nuchal translucency > 3.0 mm, and were included in
      the study at the referring obstetrician's request. None of the 80 fetuses with an
      increased nuchal translucency and normal karyotype demonstrated a 22q11
      microdeletion. By Fisher exact test, the probability of 80 fetuses with excess
      nuchal translucency having no deletions of chromosome 22 was not significantly
      different than the expected rate of 0.18% (P value = 1). CONCLUSION: Routine
      22q11 microdeletion analysis for fetuses with excess nuchal translucency is not
      indicated. Instead, we recommend storing an extra unbanded slide from the
      cultured CVS material to permit 22q11 FISH analysis should a cardiac malformation
      be identified later by fetal echocardiography.

PMID- 16458656
TI  - Do racial and ethnic differences in serum folate values exist after food
      fortification with folic acid?
AB  - OBJECTIVE: The United States food supply has been fortified with folic acid since
      1998. Information about folate levels early in pregnancy before the fortification
      is limited. This study examined the associations between serum folate at first
      prenatal visit and maternal race/ethnicity, age, vitamin use, and body mass
      index. STUDY DESIGN: This cross-sectional study assessed serum folate levels
      among 9421 women who entered prenatal care in 1999 and 2000 in southern
      California. Information on race/ethnicity, vitamin use, weight, height, and age
      was obtained from surveys and birth certificates. RESULTS: After adjustment for
      vitamin use, the strongest predictor of serum folate level, being in the lowest
      folate quartile (< or = 16 ng/mL) was related independently to being of black,
      Hispanic, or Asian/Pacific Islander race/ethnicity, being younger age, and being
      overweight or obese. CONCLUSION: After food fortification with folic acid,
      differences in serum folate values in pregnant women by maternal race/ethnicity,
      age, and body mass index persisted.

PMID- 16458655
TI  - The effects of prophylactic iron given in prenatal supplements on iron status and
      birth outcomes: a randomized controlled trial.
AB  - OBJECTIVE: The hypothesis that daily use of a prenatal supplement with iron from
      enrollment to third trimester to initially iron-replete, nonanemic pregnant women
      would reduce third-trimester anemia and improve birth outcomes was tested. STUDY
      DESIGN: Eight hundred sixty-seven women in Raleigh, North Carolina, who were at <
      20 weeks of gestation were enrolled; 429 of these women had hemoglobin levels of
      > or = 110 g/L and ferritin levels of > or = 40 microg/L and were assigned
      randomly to receive prenatal supplements with 30 mg of iron as ferrous sulfate (n
      = 218 women) or 0 mg of iron (n = 211 women) until 26 to 29 weeks of gestation.
      Intent-to-treat analysis was used for the outcomes of third-trimester iron
      status, birth weight, preterm birth, and small-for-gestational age. RESULTS: Mean
      birth weight was higher by 108 g (P = .03), and the incidence of preterm delivery
      was lower (8% vs 14%; P = .05) in the 30-mg group compared with the control
      group, respectively. Iron supplementation did not affect the prevalence of small
      for-gestational age infants or third-trimester iron status. CONCLUSION:
      Prophylactic iron supplementation that is begun early in pregnancy among low
      income women in the United States may have benefits beyond the reduction of iron
      deficiency anemia during pregnancy.

PMID- 16458657
TI  - Uterine dehiscence in term pregnant patients with one previous cesarean delivery:
      growth factor immunoexpression and collagen content in the scarred lower uterine
      segment.
AB  - OBJECTIVE: This study aimed at investigating the relationship between the
      occurrence of uterine dehiscence in term pregnant scarred uteri and the presence
      of altered biochemical behavior of the scarring process. STUDY DESIGN: Collagen
      content and the expression of transforming growth factor-beta and its isoforms
      transforming growth factor-beta1 and transforming growth factor-beta3, connective
      tissue growth factor, basic fibroblast growth factor, vascular endothelial growth
      factor, platelet-derived growth factor, and tumor necrosis factor-alpha in
      myometrium of lower uterine segment were assessed in 19 otherwise healthy term
      patients with one previous cesarean delivery who were not in labor. We were
      searching for differences between patients who showed uterine dehiscence (9
      cases) and patients who showed a normal-appearing scarred lower uterine segment
      (10 cases). We also evaluated all these features in lower uterine segment from
      unscarred uteri of 10 otherwise healthy patients who were not in labor. RESULTS:
      In the case of uterine dehiscence, the scarred lower uterine segment showed a
      higher collagen content, a reduction of pan transforming growth factor-beta
      expression because of a marked decrease or absence of transforming growth factor
      beta3, a reduction of connective tissue growth factor, an increase in basic
      fibroblast growth factor and a slight enhancement in vascular endothelial growth
      factor, platelet-derived growth factor, and tumor necrosis factor-alpha
      expression. CONCLUSION: These findings contribute to meliorate our knowledge
      about uterine scar healing and allow us to hypothesize that uterine dehiscence of
      a scarred uterus may be related to altered biochemical behavior of the scarring
      process.

PMID- 16458658
TI  - Cytomegalovirus infection of trophoblast cells elicits an inflammatory response:
      a possible mechanism of placental dysfunction.
AB  - OBJECTIVE: We sought to determine whether cytomegalovirus infection of
      extravillous trophoblast cells induces inflammatory changes that lead to cell
      death. STUDY DESIGN: Extravillous trophoblast (HTR-8/SVneo) cells were infected
      with cytomegalovirus. Cell death assays were performed 8 to 48 hours after
      infection. The expression and secretion of cytokines (interleukin-6 and -8)
      preceding cell death was measured by polymerase chain reaction and enzyme-linked
      immunosorbent assay. RESULTS: Cell viability (lactate dehydrogenase assay) was
      reduced approximately 20%, and rates of apoptosis (measured by TdT-mediated dUTP
      X nick end labeling [TUNEL] assay) were increased approximately 40% at 16 to 48
      hours after infection. Significantly elevated levels of caspase-3 mRNA levels
      were observed before increased cell death. Interleukin-6 and -8 mRNA expression
      and protein secretion were up-regulated 8 to 16 hours after cytomegalovirus
      infection. CONCLUSION: Placental exposure to cytomegalovirus induces an
      inflammatory response that precedes invasive trophoblast cell death.
      Cytomegalovirus may prevent normal placental invasion, which results in adverse
      reproductive outcomes that are associated with placental dysfunction.

PMID- 16458659
TI  - Fetal oxygenation and Doppler ultrasonography of cardiovascular hemodynamics in a
      chronic near-term sheep model.
AB  - OBJECTIVE: We hypothesized that a decrease in fetal oxygenation without acidemia
      in a near-term fetal sheep leads to cardiovascular hemodynamic changes that are
      detectable by Doppler ultrasonography. STUDY DESIGN: Twelve ewes and fetuses were
      instrumented at 112 to 127 days of gestation. After a 5-day recovery period,
      experiments were performed with general anesthesia. Uterine and placental volume
      blood flows and fetal arterial and venous blood pressures were measured. Fetal
      cardiovascular hemodynamics was assessed by Doppler ultrasonography. All the
      measurements were performed at baseline, during fetal hypo-oxygenation, and at
      recovery phase. RESULTS: A drop in fetal Po2 was related to increased (P < .05)
      weight-indexed right ventricular and combined cardiac outputs and proximal branch
      pulmonary artery pulsatility index values. The increase in proximal branch
      pulmonary artery pulsatility index values correlated (R = .59; P < .05) with the
      decrease in fetal oxygen saturation. In the aortic isthmus, the time-velocity
      integral ratio between antegrade and retrograde blood flow components decreased
      (P < .05) when fetal Po2 dropped. CONCLUSION: During decreased fetal oxygenation
      Doppler ultrasonography demonstrated increased fetal cardiac output and pulmonary
      arterial vascular impedance and a relative increase in the retrograde blood flow
      component in the aortic isthmus.

PMID- 16458660
TI  - Circulating angiogenic factors in preeclampsia, gestational proteinuria, and
      preeclampsia superimposed on chronic glomerulonephritis.
AB  - OBJECTIVE: Recently, reports have indicated that the imbalance of circulating
      angiogenic factors is important in the onset of preeclampsia. In this study we
      investigated angiogenic factor levels in women with preeclampsia, preeclampsia
      superimposed on chronic glomerulonephritis, gestational proteinuria, and normal
      pregnancies. STUDY DESIGN: We measured several circulating angiogenic factors,
      placental growth factor, vascular endothelial growth factor, soluble fms-like
      tyrosine kinase-1, and soluble fetal liver kinase-1. RESULTS: Compared with women
      with normal pregnancies, placental growth factor concentrations were lower, and
      soluble fms-like tyrosine kinase 1 concentrations were higher in women with
      preeclampsia and gestational proteinuria; soluble fms-like tyrosine kinase 1
      concentrations were also higher in women with preeclampsia superimposed on
      chronic glomerulonephritis. CONCLUSION: There were obvious differences in the
      levels of circulating angiogenic factors placental growth factor and soluble fms
      like tyrosine kinase 1 among preeclampsia, gestational proteinuria, and controls.
      The imbalance of angiogenic factors is important in the onset of preeclampsia
      superimposed on chronic glomerulonephritis.

PMID- 16458661
TI  - Divergent trophoblast invasion and apoptosis in placental bed spiral arteries
      from pregnancies complicated by maternal anemia and early-onset
      preeclampsia/intrauterine growth restriction.
AB  - OBJECTIVE: Impaired trophoblast invasion into spiral arteries is associated with
      early-onset intrauterine growth restriction and preeclampsia. We compared
      trophoblast invasion into spiral arteries in pregnancies with maternal anemia or
      early-onset preeclampsia/intrauterine growth restriction and related these
      findings to trophoblast apoptosis. STUDY DESIGN: Full-thickness uterine wall
      samples were obtained from women with early-onset preeclampsia/intrauterine
      growth restriction (n = 6), normal pregnancies (n = 5), and chronic anemia (n =
      8). Trophoblast invasion into the walls of spiral arteries was quantified by
      morphometric analysis of paraffin sections stained with anticytokeratin 18,
      antiactin, and anticytokeratin 18 neoepitope (M30) antibodies. RESULTS:
      Trophoblast invasion into spiral arteries was increased in anemic pregnancies
      (mean [SD]: 206 [46] cell profiles/mm2) and severely impaired in
      preeclamptic/intrauterine growth restriction pregnancies (17 [6]), compared with
      normal subjects (149 [52]). Spiral artery lumen area was increased in anemia
      (0.07 [0.03] mm2) versus normal pregnancies (0.09 [0.04] mm2) and reduced in
      preeclampsia/intrauterine growth restriction (0.04 [0.02] mm2). Trophoblast
      apoptosis was similar in anemic (4.2% [3.4%]) and normal (5.0% [1.9%])
      pregnancies but increased in preeclampsia/intrauterine growth restriction (12%
      [5.6%]). CONCLUSION: Trophoblast invasion into the placental bed in early-onset
      preeclampsia/intrauterine growth restriction is limited by increased apoptosis,
      resulting in narrower spiral arteries, which is in contrast to findings in
      anemia.

PMID- 16458662
TI  - Differential expression of angiopoietin-1, angiopoietin-2, and Tie receptors in
      placentas from pregnancies complicated by placenta accreta.
AB  - OBJECTIVE: The purpose of this study was to investigate the differential
      expression of angiopoietin-1, angiopoietin-2, and Tie receptors (Tie-1 and Tie-2)
      in placentas from pregnancies complicated by placenta accreta. STUDY DESIGN:
      Paraffin sections of 46 placental specimens with (cases) and 46 without
      (controls) placenta accreta were studied immunohistochemically for the expression
      of Tie receptors and angiopoietin-2 in trophoblast populations. Protein levels of
      Tie receptors and angiopoietins were also examined by Western blot analysis
      and/or enzyme-linked immunosorbent assay. Controls were matched for gestational
      age in this case-control study. RESULTS: In both second and third trimesters, the
      percentage of intermediate/strong immunoreactivity of Tie-2 in the
      syncytiotrophoblast was significantly lower in cases than controls (P = .015 and
      .025, respectively). However, Tie-2 expression in the cytotrophoblastic and
      extravillous trophoblastic cells and Tie-1 in all trophoblast subpopulations were
      not significantly different between cases and controls (P > .05). The majority of
      Tie-2 expression, as demonstrated by Western blots, was consistent with the
      trends of immunohistochemical findings in the syncytiotrophoblast. Enzyme-linked
      immunosorbent assay in the placental lysates showed that women with placenta
      accreta demonstrated significantly higher angiopoietin-2 and lower Tie-2
      concentrations than did women with normal pregnancies (P = .026 and .003,
      respectively). Placental angiopoietin-1 levels did not have any significance (P >
      .05). Also, angiopoietin-2 immunoreactivity in the syncytiotrophoblast was
      compatible with the finding demonstrated by enzyme-linked immunosorbent assay (P
      = .005 and .012, respectively). CONCLUSION: These observations suggest that the
      participation of up-regulated angiopoietin-2 and down-regulated Tie-2 in the
      placental tissues may indicate a role for these angiogenic factors in the
      development of placenta accreta.

PMID- 16458663
TI  - Betamethasone effects on ovine uterine and umbilical placental perfusion at the
      dose used to enhance fetal lung maturation.
AB  - OBJECTIVE: The purpose of this study was to examine glucocorticoid effects on
      umbilical placental perfusion. STUDY DESIGN: Pregnant sheep instrumented with
      uterine and umbilical ultrasound transit-time flow probes received 2 doses of 12
      mg betamethasone (n = 6) or saline (n = 5) intramuscularly 24 hours apart.
      RESULTS: Maternal blood pressure and uterine flow did not change during
      glucocorticoid exposure. Fetal blood pressure increased, and umbilical resistance
      showed a transient increase after each injection (P < .05), followed by an
      increase of umbilical flow (P < .05) that was closely correlated to an increase
      in fetal heart rate (r = 0.85, P < .001), which determines cardiac output of the
      developing heart. Umbilical waveform indices were decreased over the entire
      treatment period, indicating a decrease of resistance in the fetoplacental
      microcirculation (P < .05). CONCLUSION: Fetoplacental perfusion during
      glucocorticoid exposure is not limiting for nutrition exchange. Clinical
      interpretation of Doppler waveform indices needs to be interpreted with caution
      because they do not reflect dynamics of umbilical placental perfusion.

PMID- 16458664
TI  - Dietary vitamin and lipid therapy rescues aberrant signaling and apoptosis and
      prevents hyperglycemia-induced diabetic embryopathy in rats.
AB  - OBJECTIVE: Maternal diabetes causes developmental malformations in the embryo.
      Dietary supplementation with antioxidants can reduce the malformation rates in
      animal models. To investigate the molecular mechanisms underlying diabetes
      induced embryonic abnormalities and dietary interventions, activity of mitogen
      activated protein kinases and factors associated with apoptotic pathways were
      examined in the maternal diabetic rat model. STUDY DESIGN: Diabetes was induced
      in pregnant rats using streptozotocin. In the yolk sacs of the embryos, activity
      of the extracellular signal-regulated kinases, Raf-1, and Akt was dramatically
      reduced in diabetic rats, whereas that of c-jun N-terminal kinases/stress
      activated protein kinases was increased. RESULTS: When the diabetic dams were fed
      with arachidonic acid, vitamin E, or a combination of arachidonic acid, vitamin
      E, and myoinositol, the changes in the expression of these kinases were reversed
      and correlated with the decreases in the rates of apoptosis and embryonic
      malformations. CONCLUSION: These results suggest that mitogen-activated protein
      kinases are involved in diabetic embryopathy, and dietary supplementations can
      rescue the aberrant signaling pathways and reduce embryonic malformation rate.

PMID- 16458665
TI  - Amniography. Preliminary report. 1930.

PMID- 16458667
TI  - Why and how we started amniography. 1976.

PMID- 16458668
TI  - Risk factors for Toxoplasma gondii infection in mothers of infants with
      congenital toxoplasmosis: implications for prenatal management and screening.

PMID- 16458671
TI  - Comparing McRoberts' and Rubin's maneuvers for initial management of shoulder
      dystocia: an objective evaluation.

PMID- 16458672
TI  - The benefit of combined maternal administration of magnesium sulfate and
      aminophylline.

PMID- 16458673
TI  - Neuroprophylaxis with aminophylline and magnesium sulfate?

PMID- 16458675
TI  - Long-term changes in corneal surface configuration after penetrating
      keratoplasty.
AB  - PURPOSE: To examine the long-term longitudinal changes in corneal surface
      configuration as determined by Fourier series harmonic analysis of
      videokeratography data and of visual acuity and refraction after penetrating
      keratoplasty (PK). DESIGN: Interventional case series. METHODS: One hundred
      thirty eyes of 130 consecutive patients who were scheduled for PK using 16
      interrupted 10-0 nylon sutures were recruited. Spherical equivalent power,
      regular astigmatism component, irregular astigmatism (asymmetry and higher-order
      irregularity) component of the central cornea as determined by Fourier analysis
      of videokeragraphic data, spectacle-corrected visual acuity, and spherical
      equivalent were examined at 1 week, and at 1, 3, 6, 9, 12, 18, and 24 months
      after PK. RESULTS: Spherical equivalent power increased considerably for up to 1
      month after PK, but thereafter showed no further appreciable change up to the
      final follow-up at 24 months. The regular astigmatism component decreased
      markedly for up to 6 months after PK, while the total irregular astigmatism (sum
      of the asymmetry and higher-order irregularity) component decreased considerably
      up to approximately 3 months, and then these showed no further relevant change
      for up to 24 months. Spectacle-corrected visual acuity also improved markedly
      until approximately 3 months after PK, after which it was virtually stable.
      Furthermore, important correlations were found between regular and irregular
      astigmatism and the spectacle-corrected visual acuity. CONCLUSIONS: Corneal
      surface configuration after PK appears to be stable by approximately 6 months
      after PK, concurrent with postkeratoplasty stabilization of visual acuity.

PMID- 16458676
TI  - Visual field defects and retinal nerve fiber layer defects in eyes with buried
      optic nerve drusen.
AB  - PURPOSE: To evaluate the visual field with the use of automated perimetry and to
      evaluate the retinal nerve fiber layer (RNFL) with optical coherence tomography
      (OCT) in patients with buried optic nerve drusen (OND). DESIGN: Observational
      case control study. METHODS: Eyes with buried OND were defined as eyes with
      ultrasound-proved drusen that were not visible with indirect slit-lamp
      biomicroscopy. All eyes underwent automated perimetry. Some eyes underwent OCT to
      evaluate the RNFL. RESULTS: Fifty-eight eyes of 41 patients with buried OND were
      evaluated. Three eyes (5%) had inferior arcuate scotomas. The other 55 eyes did
      not have visual field defects. Twenty-one of the eyes without visual field
      defects underwent RNFL analysis with OCT. All 21 eyes had normal average RNFL
      thickness. Some eyes had focal RNFL defects, but it is not clear whether these
      defects were clinically significant. CONCLUSION: Visual field defects are
      uncommon in eyes with buried OND. Eyes with buried OND may have focal RNFL
      defects but have normal average RNFL thickness. In patients with buried OND and a
      visual field defect, consideration should be given to searching for other causes
      of the defect, especially if the defect is substantial.

PMID- 16458677
TI  - Results of deep lamellar keratoplasty using the big-bubble technique in patients
      with keratoconus.
AB  - PURPOSE: To evaluate the efficacy of deep lamellar keratoplasty using the big
      bubble technique in patients with keratoconus. DESIGN: Interventional case
      series. METHODS: Thirteen eyes of 12 patients (eight male and four female
      subjects) with moderate to advanced keratoconus and intolerance to contact lens
      wear were included in this study. Deep lamellar keratoplasty was performed by the
      intrastromal air injection technique. Full-thickness donor tissue devoid of
      Descemet membrane and endothelium was then sutured into place. Best-corrected
      visual acuity, refractive results, surgical technique, and complication rates
      were analyzed. RESULTS: Big bubble was successfully achieved in nine eyes
      (69.2%). Average postoperative best-corrected visual acuity was 20/25 (range
      20/50 to 20/20) at a mean follow-up of 5 months. Intraoperative microperforation
      of Descemet membrane occurred in two eyes (15.3%). Three eyes (23%) developed a
      steroid-induced increase in intraocular pressure, which responded to medical
      therapy. CONCLUSIONS: Deep lamellar keratoplasty that uses the big-bubble
      technique is safe and effective in patients with keratoconus. Visual outcome is
      comparable to standard penetrating keratoplasty, without the risk of endothelial
      rejection.

PMID- 16458678
TI  - Surgery-related factors influencing corneal neovascularization after low-risk
      keratoplasty.
AB  - PURPOSE: To identify the speed of corneal neovascularization (CNV) after
      penetrating keratoplasty (PK) and to evaluate the influence of surgery-related
      factors on postkeratoplasty CNV in keratoconus patients. DESIGN: Prospective,
      longitudinal, observational, case series study. METHODS: All consecutive primary
      PKs performed for keratoconus by four experienced surgeons between January 1,
      2000 and December 31, 2002 at our department were included (n=66 patients).
      Standardized corneal photographs taken preoperatively and at 6 weeks, 3, 6, 12,
      18, and 24 months postoperatively were evaluated. Limbus suture distance (LSD),
      limbus graft distance (LGD), inner suture angle (ISA), and maximal extension of
      CNVs in digitized pictures with 100-fold magnification were measured at each of
      the 16 suture turning points at every timepoint. RESULTS: Forty-four (67%) out of
      66 corneal grafts developed some degree of CNV after PK, most commonly from
      around the 12 o'clock position. The mean speed of CNV growth was 114 microm/month
      with the fastest growth occurring during the first six weeks after PK. There was
      an inverse correlation between CNV and LSD, LGD, and ISA (all P<.001). Ninety
      percent of all CNVs developed with LSD<406 microm and with LGD<1000 microm.
      Superior limbal localization between 11 and 1 o'clock is an independent risk
      factor for postoperative neovascularization, too (P<.001). CONCLUSIONS: Small
      LSD, small LGD, and narrow stitching with small ISA were identified as
      potentially modifiable surgical risk factors for CNV after PK. The speed of CNV
      outgrowth was most pronounced in the first weeks after PK making early
      postoperative controls for CNV growth and initiation of antiangiogenic treatment
      important.

PMID- 16458679
TI  - Midterm results on ocular surface reconstruction using cultivated autologous oral
      mucosal epithelial transplantation.
AB  - PURPOSE: To perform a midterm assessment of the integrity and reproducibility of
      cultivated autologous oral mucosal epithelial sheets, and to evaluate the
      clinical efficacy of their transplantation in ocular surface. DESIGN:
      Observational case series. METHODS: Cultivated autologous oral mucosal epithelial
      sheets were created using amniotic membrane and buccal mucosal epithelium from 12
      patients with Stevens-Johnson syndrome, chemical and thermal injury, pseudo
      ocular cicatricial pemphigoid, and idiopathic ocular surface disorder. They were
      transplanted onto 15 eyes from these patients who were then followed up for a
      mean of 20 months; with the longest follow-up being 34 months. We assessed their
      clinical outcomes with special reference to neovascularization. RESULTS:
      Cultivated autologous oral mucosal epithelial sheets could be generated from all
      patients. On the second postoperative day, 14 of 15 sheets transplanted
      demonstrated total re-epithelialization on the cornea. During the follow-up, the
      ocular surface was stable and transparent without any major complications in 10
      of 15 eyes (67%), and the transplanted epithelium survived for at least 34
      months. There were five eyes (33%) with small but long-standing epithelial
      defects, three of these healed spontaneously, and two (13%) required reoperation.
      In 10 eyes, postoperative visual acuity was improved by more than 2 lines. All
      eyes manifested some peripheral corneal vascularization. CONCLUSIONS: We
      established a successful tissue-engineering technique to generate cultivated
      autologous oral mucosal epithelial sheets and succeeded in reconstructing the
      ocular surface. We suggest that this surgical modality may be both safe and
      useful, especially in younger patients with the most severe ocular surface
      disorders.

PMID- 16458680
TI  - Prophylactic laser treatment hastens choroidal neovascularization in unilateral
      age-related maculopathy: final results of the drusen laser study.
AB  - PURPOSE: The Drusen Laser Study evaluated macular laser to prevent choroidal
      neovascularization (CNV) and vision loss in high-risk age-related maculopathy
      (ARM). DESIGN: Prospective, interventional, randomized, controlled clinical trial
      in five hospital centers. METHODS: Patients in the unilateral group had
      neovascular ARM and drusen in the study eye. Study eyes were randomized to laser
      treated or no-laser groups. For patients in the bilateral drusen group, eyes were
      randomized to right eye, laser or no laser; and left eye, alternative. Laser
      treatment comprised 12 argon spots. Outcome was best-corrected visual acuity and
      CNV signs, which were monitored for 3 years. RESULTS: In the unilateral group,
      vision loss occurred in 21 (28.8%) of 73 patients in laser vs 13 (19.7%) of 66 no
      laser patients (P=.214). Incidence of CNV was 27 (29.7%) of 91 in laser vs 15
      (17.65%) of 85 no-laser patients (P=.061). CNV onset was approximately 6 months
      earlier in laser-treated compared with no-laser patients (P=.05). In the
      bilateral group, vision loss occurred in six (8.3%) of 72 laser-treated vs 10
      (13.9%) of 72 fellow eyes (P=.3877). CNV incidence was 12 (11.6%) of 103 in laser
      treated vs seven (6.8%) of 103 fellow eyes (P=.225). There was no difference in
      onset of CNV. CONCLUSIONS: Results do not support prophylactic laser of the
      fellow eye of patients with neovascular ARM. Its role in patients with bilateral
      drusen remains unclear.

PMID- 16458681
TI  - Comparison of topical gatifloxacin 0.3% and ciprofloxacin 0.3% for the treatment
      of bacterial keratitis.
AB  - PURPOSE: To compare the bacteriologic and clinical efficacy of gatifloxacin and
      ciprofloxacin for the treatment of bacterial keratitis. DESIGN: Prospective,
      randomized clinical trial. METHODS: A total of 104 eyes of 104 patients with
      bacterial keratitis seen at a tertiary eye-care center were randomized to
      treatment with gatifloxacin 0.3% eyedrops (GAT group, 50 eyes) or ciprofloxacin
      0.3% eyedrops (CIP group, 54 eyes). Patients and the treating physician were
      masked to the antibiotic being used. Main outcome measure studied was healing of
      the ulcer. Patients lost to follow-up before complete healing were excluded from
      further analysis. RESULTS: A significantly higher proportion of ulcers in the GAT
      group exhibited complete healing compared with those in the CIP group (39 eyes
      [95.1%] vs 38 [80.9%]; P=.042). Gatifloxacin demonstrated a significantly better
      action than ciprofloxacin against gram-positive cocci in vitro (P<.001), and the
      percentage of ulcers caused by these pathogens that healed in the GAT group was
      significantly better than in the CIP group (P=.009). Mean time taken for healing
      of ulcer and the efficacy against gram-negative bacteria did not significantly
      differ between the two groups. CONCLUSIONS: Gatifloxacin had a significantly
      better action against gram-positive cocci both in vitro and in vivo when compared
      with ciprofloxacin. In view of these organisms being the leading cause of
      keratitis worldwide, gatifloxacin may be a preferred alternative to ciprofloxacin
      as the first-line monotherapy in bacterial keratitis.

PMID- 16458682
TI  - Changes in corneal power and refraction due to sequential suture removal
      following nonmechanical penetrating keratoplasty in eyes with keratoconus.
AB  - PURPOSE: To assess the changes in corneal power and refraction due to sequential
      suture removal after penetrating keratoplasty (PK). DESIGN: Retrospective
      consecutive case series. METHODS: setting: Clinical practice. study population:
      We studied 67 phakic keratoconus eyes (central excimer laser trephination,
      primary keratoplasty, graft/recipient diameter 8.1/8.0 mm; double running suture)
      in this longitudinal study. main outcome measures: Zeiss keratometry (equivalent
      power (KEQ), astigmatism (KAST)), corneal topography (equivalent power (TEQ),
      astigmatism (TAST)) and subjective refractometry (spherical equivalent (SEQ),
      refractive cylinder (RAST)) were assessed with sutures in place (interval 1),
      with one suture out (interval 2), and with all sutures out (interval 3).
      observation procedure: Corneal power and refraction was decomposed into vector
      components and the changes were derived between time stages. RESULTS: The mean
      follow-up period was 3.9+/-1.7 years. At interval 1, the axes of KAST/TAST/RAST
      were almost randomly distributed. At interval 2, the with/against the rule
      component of KAST/TAST/RAST decreased slightly and the oblique component
      increased significantly, so that the axes tended to have a preferred oblique
      direction. At interval 3, the with/against the rule component of KAST/TAST/RAST
      increased slightly and the oblique component decreased significantly, so that the
      with/against the rule component exceeded the oblique component by approximately
      23%/28%/25%. Median KEQ/TEQ/SEQ changed by 0.64/0.62/-1.11 diopters (interval 1
      to interval 2) and by -0.85/-0.90/1.56 diopters (interval 2 to interval 3).
      CONCLUSIONS: As a result of removal of the first running suture, corneal
      astigmatism as well as the refractive cylinder tend to oblique axes. As a result
      of removal of the second running suture, the final corneal astigmatism and
      refractive cylinder tend to orientation axes with/against the rule.

PMID- 16458683
TI  - Ultraviolet fluorescence photography to detect early sun damage in the eyes of
      school-aged children.
AB  - PURPOSE: To develop a method to detect precursors of ocular sun damage using
      ultraviolet fluorescence photography (UVFP). DESIGN: Observational cross
      sectional study METHODS: settings: Preschool, primary, and high school in Sydney,
      Australia. study population: 71 children ages 3 to 15 years old (both eyes).
      Inclusion criteria were children attending the schools who gave consent. There
      were no exclusion criteria. observation procedures: UV and standard (control)
      photographs were taken of the nasal and temporal interpalpebral regions
      bilaterally. main outcome measures: Presence of areas of increased fluorescence
      detected by UVFP, or presence of pinguecula detected by standard photography.
      RESULTS: Established pingueculae, on standard photography, were seen in seven of
      71 (10%) children; all were 13 years of age or older. On UVFP, all of these
      pingueculae demonstrated fluorescence. In total, 23 of 71 (32%) had increased
      fluorescence detected on UVFP, including the seven of 23 (30%) with pingueculae.
      Of the remaining 16 of 23 (70%), the changes were only detectable using UVFP.
      Fluorescence on UVFP was seen in children ages 9 years and above, with prevalence
      increasing with age. The presence of fluorescence (in at least one region) was 0
      of 15 (0%) for children ages 3 to 5 years, 0 of 12 (0%) of children ages 6 to 8
      years, 6 of 23 (26%) for those ages 9 to 11 years, and 17 of 21 (81%) of those
      ages 12 to 15 years. CONCLUSIONS: We hypothesize that the areas seen to fluoresce
      on UVFP but not detectable on control photography represent precursors for
      ophthalmohelioses. Our preliminary data strongly suggests that UVFP is a
      sensitive method for detecting early ocular sun damage occurring many years
      before clinical manifestations.

PMID- 16458684
TI  - Ocular surface restoration using non-surgical transplantation of tissue-cultured
      human amniotic epithelial cells.
AB  - PURPOSE: To assess the effect of tissue-cultured human amniotic epithelial cells
      (AECs) in restoring the ocular surface, transplanted using a collagen shield
      seeded with AECs supported by a soft contact lens. DESIGN: Prospective
      interventional single-institutional case series with crossover controls. METHODS:
      Three eyes in three patients were identified with persistent corneal epithelial
      defects (PEDs) refractory to medical therapy. Two cases were secondary to
      neurotrophic keratopathy, while one case was attributable to longstanding alkali
      injury. AECs were isolated from serologically screened donor human placenta,
      seeded onto collagen corneal shields, and incubated in tissue culture medium for
      7 days. These collagen shields were placed over the PED and supported by an
      overlying soft contact lens. The collagen shields dissolved by 72 hours, and the
      contact lenses were removed after this time. This cycle was repeated every week
      until healing was achieved. As a crossover control, collagen shields without AECs
      were placed in the same eye 1 week before placing collagen shields containing
      AECs. The PED was assessed by vital staining and slit-lamp color photography.
      RESULTS: The PEDs had a mean duration of 4 months and involved 20% to 37% of the
      corneal surface area, one case secondary to longstanding alkali injury and two
      cases attributable to neurotrophic keratopathy. No change in PED size was
      observed in those control eyes receiving collagen shields without AECs. Complete
      resolution of the PED was seen after two cycles of AEC-seeded collagen shield in
      one case, and four cycles in two cases, from 7 to 12 weeks following treatment in
      all patients. No loss of visual acuity was seen and clinical improvement was
      maintained in all cases, with a mean follow-up of 6.3 months. CONCLUSIONS:
      Nonsurgical transplantation of tissue-cultured AECs on a collagen shield provides
      a promising approach to restoring the ocular surface in cases of PED.

PMID- 16458685
TI  - Long-term outcome of combined pars plana vitrectomy and scleral fixated sutured
      posterior chamber intraocular lens implantation.
AB  - PURPOSE: To investigate the long-term visual outcome and the complication rate
      following transscleral suture fixation of posterior chamber intraocular lenses
      (sutured PC-IOLs). DESIGN: A retrospective case-series descriptive study.
      METHODS: Records of patients who underwent combined pars plana vitrectomy and
      sutured PC-IOLs at Moorfields Eye Hospital and who had at least 12 months of
      follow-up were examined for recorded complications. RESULTS: Sixty-one eyes of 48
      patients (33 males and 15 females) were identified and included in the analysis,
      with mean follow-up of 6 years. The mean final best-corrected visual acuity
      remained at preoperative levels (P=.211) and was largely determined by the
      underlying ocular pathology before sutured PC-IOL. Overall 30 of 61 (49%) eyes,
      two or more procedures were performed to reverse a significant peri- or
      postoperative complication. Breakage of polypropylene sutures was the main
      indication accounting for 17 of 30 (57%) of those reoperations. Subgroup analysis
      showed that younger patients were more likely to suffer the above complication
      (P=.009). The multivariate analysis also showed that longer follow-up was
      significantly associated with suture breakage (P=.014), with the mean time to
      breakage approximately 4 years after surgery. CONCLUSIONS: Long-term follow-up of
      patients undergoing sutured PC-IOLs appears to be associated with a high rate of
      postoperative complications and significant need for further surgery, which
      should be discussed during their informed consent process.

PMID- 16458687
TI  - Adult-onset syphilitic stromal keratitis.
AB  - PURPOSE: To characterize the clinical features and therapeutic outcome of stromal
      keratitis associated with syphilis in adults. DESIGN: Observational case series.
      METHODS: We examined the clinical and laboratory records at a single center of
      individuals with active stromal keratitis who had serological evidence of
      syphilis by a treponemal specific test. RESULTS: Five patients, 36 to 81 years of
      age, developed stromal keratitis during late syphilis. One patient with
      developmental signs of congenital syphilis had bilateral stromal keratitis. The
      others were otherwise healthy when they presented with unilateral, nonulcerative,
      infiltrative keratitis with stromal edema of the peripheral or paracentral cornea
      and mild to moderate corneal vascularization. All had an appropriate response to
      topical corticosteroid therapy, and two recovered good vision. Stromal keratitis
      recurred in two patients months to years later. CONCLUSIONS: Nonulcerative
      stromal keratitis presents in adults with syphilis as marginal, central, or
      multifocal stromal inflammation with neovascularization that responds to
      corticosteroid therapy but occasionally recurs.

PMID- 16458686
TI  - Polymerase chain reaction and Goldmann-Witmer coefficient analysis are
      complimentary for the diagnosis of infectious uveitis.
AB  - PURPOSE: To determine the relative contribution of the analysis of intraocular
      antibody production and the polymerase chain reaction (PCR) in aqueous humor (AH)
      to the diagnosis of infectious uveitis. DESIGN: Retrospective case-control study.
      METHODS: Paired AH and serum samples from 230 patients suspected of infectious
      uveitis were examined for intraocular antibody production against herpes simplex
      virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii by calculating
      the Goldmann-Witmer coefficient (GWC). In addition, AH samples were investigated
      by real-time PCR to determine the presence of microbial DNA. RESULTS: Positive
      results were obtained in 54 cases (23%): 13 HSV (24%), 16 VZV (30%), and 25 T
      gondii (46%). Of these, 23 (43%) were positive for both GWC and PCR, 26 (48%)
      only for GWC, and 5 (9%) only for PCR. With PCR as the sole diagnostic approach,
      a correct diagnosis of the infectious etiology would have been missed in 34% of
      cases for the herpes viruses and in 64% for T gondii. Analysis of the
      relationship between a positive laboratory diagnosis and the time of sampling
      after onset of ocular disease demonstrated that intraocular antibody production
      was found throughout the course of the diseases. Viral DNA was more readily
      detected early in infection. In contrast, T gondii nucleic acid was not detected
      until 3 weeks after onset of ocular disease. CONCLUSIONS: Analysis of intraocular
      antibody production contributed considerably to the etiological diagnosis of
      infectious uveitis, most notably of ocular toxoplasmosis early after onset of
      disease. Therefore, both PCR and GWC determination might be performed for
      comprehensive diagnosis of intraocular infections.

PMID- 16458688
TI  - Thermal imaging study comparing phacoemulsification with the Sovereign with
      WhiteStar system to the Legacy with AdvanTec and NeoSoniX system.
AB  - PURPOSE: To assess intraoperative thermal levels at the wound site during divide
      and-conquer phacoemulsification with the Sovereign with WhiteStar (SWS) system or
      the Legacy with AdvanTec and NeoSoniX (LAD) system. DESIGN: Prospective,
      randomized, parallel-group, comparative study. METHODS: Twenty-six subjects from
      a private clinical practice underwent divide-and-conquer phacoemulsification with
      either the SWS system or the LAD system. CB/CF settings (60%/33% duty cycles)
      were utilized with SWS and 12 pulses per second with the LAD system. Key criteria
      assessed were peak wound-site temperature, mean temperature change at the wound
      site, effective phaco time, average phaco power, procedure time, amount of BSS
      used, and surgical complications. RESULTS: Mean temperature change at the wound
      site was greater for the LAD than the SWS group. There was a statistically
      significant difference (P=.0002) in mean peak wound temperatures, with the LAD
      group having higher mean peak temperatures (42.47+/-5.33 degrees C) than the SWS
      group (36.59+/-1.33 degrees C). Highest wound-site temperature was 51 degrees C
      for the LAD group and 39.3 degrees C for the SWS group. A statistically
      significant difference (P=.0031) in mean peak temperature was found between the
      LAD and SWS systems for subjects with a cataract density of 4: higher mean peak
      temperatures were observed for LAD patients with a cataract density of 4.
      CONCLUSIONS: Our findings show that phacoemulsification using the SWS system
      results in lower peak temperatures and less temperature change at the phaco wound
      site compared with the LAD system.

PMID- 16458689
TI  - Objective measurement of visual acuity by optokinetic response determination in
      patients with ocular diseases.
AB  - PURPOSE: To investigate the efficacy of optokinetic nystagmus (OKN) suppression
      and induction methods for the objective estimation of visual acuities in patients
      with various ocular diseases. DESIGN: Prospective, descriptive study. METHODS:
      One hundred seventy-three eyes of 89 patients aged between 27 and 75 years who
      registered at our institution from January to December 2004 were prospectively
      enrolled onto this study. Ocular diseases included generalized retinal diseases
      (47 eyes), media opacity (32 eyes), refractive errors (31 eyes), glaucoma (27
      eyes), maculopathies (26 eyes), and optic neuropathies (10 eyes). Horizontal
      optokinetic stimuli were presented on a 17-inch monitor screen at a distance of
      40 cm from the subject in a dark room. Horizontal eye movements were recorded in
      each eye separately by infrared oculography. Objective visual acuities measured
      by using OKN suppression or induction methods were compared with subjective
      visual acuity assessments. The logarithm of minimal angle of resolution visual
      acuity was 1.03, and ranged from -0.08 to hand movement. RESULTS: Linear
      regression identified minimum stripe stimuli required to induce OKN by using the
      OKN induction method, and the minimum dot size required to suppress OKN was found
      to be correlated with subjective visual acuity (P<.01). The induction method was
      useful in patients with visual acuities of 20/60 or worse, and the suppression
      method was useful in patients with visual acuities of 20/200 or better.
      CONCLUSIONS: Combined use of the OKN induction and suppression methods provides a
      satisfactory means of determining objective visual acuity.

PMID- 16458690
TI  - Sclerosing therapy as first line treatment for low flow vascular lesions of the
      orbit.
AB  - PURPOSE: To evaluate the outcome of sodium morrhuate 5% injections in patients
      with low flow vascular lesions, which consist of orbital lymphangiomas, and in
      one patient with intraosseous cavernous hemangioma. DESIGN: Prospective,
      interventional consecutive case series. METHODS: Intralesional sodium morrhuate
      5% was injected under direct visualization or under radiographic guidance to six
      patients with orbital lymphangiomas and one patient with intraosseous cavernous
      hemangioma. Comprehensive eye examination and follow-up imaging studies were
      performed. main outcome measures: Lesion size was evaluated by orbital imaging
      and clinical examination, visual acuity, exophthalmos, and posttreatment
      complications. RESULTS: Seven patients (four female, three male; average age, 33
      years) were included. Six patients were diagnosed with orbital lymphangioma, and
      one patient was diagnosed with intraosseous cavernous hemangioma. Patients
      received an average of 2.6+/-2 intralesional injections of sodium morrhuate, with
      a range of one to six injections and a mean volume of 0.9+/-0.8 ml (range, 0.2 to
      2.1 ml). Lesions showed a decrease in size an average of 50% (33%) and ranged
      from minimal (10%) to near total resolution (85%). Visual acuity and intraocular
      pressure remained unchanged; exophthalmos decreased an average of 1.5+/-1.8 mm.
      Complications included one case of orbital hemorrhage that resolved spontaneously
      and transient keratopathy in all patients with anterior orbital lesions.
      CONCLUSION: Intralesional sclerosing therapy with sodium morrhuate 5% is
      effective in tumor debulking in patients with orbital lymphangioma and is not
      associated with vision-threatening complications. It may be a better alternative
      to surgery for low flow orbital tumors, which includes lymphangioma.

PMID- 16458691
TI  - A procedure to minimize lower lid retraction during large inferior rectus
      recession in graves ophthalmopathy.
AB  - PURPOSE: To determine whether complete detachment of the fascia of the
      capsulopalpebral head during large inferior rectus recession can help to prevent
      induced lower lid retraction in Graves ophthalmopathy. DESIGN: Retrospective
      consecutive case series. METHODS: Data from patients (39 eyes) with Graves
      ophthalmopathy undergoing inferior rectus recession were collected
      retrospectively. Inferior rectus recession was performed by limbus-based incision
      with adjustable suture. Simultaneous detachment of the fascia of the
      capsulopalpebral head was achieved by sharp dissection and severing of the
      fascia. Inferior rectus recession with simultaneous detachment of the fascia of
      the capsulopalpebral head was performed in 27 eyes and without detachment in 12
      eyes. Margin reflex distance (MRD2) was documented preoperatively and 3 months
      postoperatively. RESULTS: Of the 39 eyes included in this study, four eyes with
      preexisting lower lid retraction in the detachment group improved after surgery.
      Eighteen eyes in the detachment group exhibited the same MRD2 values, and only
      five eyes showed increased MRD2 values. In contrast, all but one of the 12 eyes
      in the nondetachment group showed increased MRD2 values. The average change in
      the MRD2 value 3 months after surgery was 0.04+/-0.59 mm in the detachment group
      and 1.58+/-0.73 mm in the nondetachment group. There was a statistically
      significant difference between the two groups (P<.01). CONCLUSIONS: Simultaneous
      detachment of the fascia of the capsulopalpebral head during inferior rectus
      recession can minimize the possibility of lower lid retraction.

PMID- 16458692
TI  - Initial results of small incision deep lamellar endothelial keratoplasty (DLEK).
AB  - PURPOSE: To evaluate the results of replacing the posterior stroma and
      endothelium, using small incision deep lamellar endothelial keratoplasty (DLEK)
      surgical technique, in patients with corneal endothelial dysfunction. DESIGN:
      Noncomparative case series. METHODS: Fifteen eyes of 15 patients (six males and
      nine females) with endothelial dysfunction were included in this study. Through a
      5-mm scleral incision, a deep lamellar pocket was created across the cornea,
      followed by excision of an 8.0-mm disk of posterior lamellar corneal tissue. Same
      size lamellar donor disk was prepared and placed in position without the need of
      suture fixation. Best spectacle-corrected visual acuity (BSCVA), refraction,
      endothelial cell density, corneal topography, and corneal thickness were
      analyzed. RESULTS: Average BSCVA preoperative was 20/200 (range 20/40 to hand
      movements (HM)), improving to 20/50 (range 20/20 to 20/120) at a mean follow-up
      of 7.2 months. Average refractive astigmatism at last follow-up was 1.46+/-1.21
      diopters (range, 0 to 4 diopters). Preoperative average donor endothelial cell
      density was 2047+/-311 cells/mm2, and that at last follow-up was 1732+/-514
      cells/mm2. Preoperative average pachymetry was 801.4+/-211.3 microm, improving to
      553+/-90.4 microm at last follow-up. CONCLUSIONS: Initial results with small
      incision DLEK procedure indicate that it is a safe procedure that provides
      healthy donor endothelial cell count and function postoperatively, with
      encouraging visual results.

PMID- 16458693
TI  - Deep lamellar keratoplasty.

PMID- 16458694
TI  - Hastening choroidal neovascularization: the irony of prophylactic laser in
      unilateral eyes with high-risk drusen.

PMID- 16458695
TI  - Move stem cells from the mouth to the eye.

PMID- 16458696
TI  - Should we be paying more attention to corneal neovascularization?

PMID- 16458697
TI  - Wavefront-guided ablation: evidence for efficacy compared to traditional
      ablation.
AB  - PURPOSE: To provide an evidence-based overview of wavefront-guided refractive
      surgery outcomes, benefits, and limitations. DESIGN: Literature review. METHODS:
      Review of FDA study reports and indexed, peer-reviewed literature. RESULTS: More
      than 400 reports investigating wavefront applications in refractive surgery
      exist, but studies comparing the outcomes of wavefront-guided treatment with
      conventional treatment are few in number. Available studies do not overwhelmingly
      demonstrate superior visual results attributable to a wavefront-guided approach.
      CONCLUSIONS: While wavefront-guided refractive surgery provides excellent
      results, evidence is limited that it outperforms conventional laser in situ
      keratomileusis that incorporates broad ablation zones, smoothing to the
      periphery, eye-trackers, and other technological refinements. However, it is
      evident that wavefront-customized ablation holds a promising future and merits
      ongoing investigation.

PMID- 16458698
TI  - Prolonging contact lens wear and making contact lens wear safer.
AB  - PURPOSE: To summarize the present status of safety and efficacy of contact lens
      wear. DESIGN: Literature review. METHODS: Ovid Medline searches were performed on
      records from 1966 through 2005 using keywords: keratitis, contact lens
      complications, extended-wear contact lenses, and silicone-hydrogel contact
      lenses. RESULTS: Patients desire comfort, clarity of vision, and prolonged
      contact lens wear when contact lenses are used to correct refractive error.
      Practitioners desire patient satisfaction but also require maintenance of the
      integrity of the eye and no complications that jeopardize vision or health of the
      eye. Improvements in the oxygen permeability of the contact lens materials,
      design of the contact lens and its surface, and solutions for the maintenance of
      the lens have reduced but not eliminated the risks of infection, inflammation,
      and conjunctival papillary reaction associated with contact lens wear. The
      lessons of past and recent history suggest that patient education and
      practitioner participation in the management of contact lens wear continue to be
      critical factors for patient satisfaction and safety in the extended wear of
      contact lenses. CONCLUSIONS: The availability of highly oxygen permeable contact
      lenses has increased the tolerance and safety of extended contact lens wear, but
      patient instruction and education in proper use and care of lenses is required
      and caution is advised.

PMID- 16458699
TI  - Langerhans cell histiocytosis of the orbit: a need for interdisciplinary
      dialogue.
AB  - PURPOSE: To explore specialty-related perceptions and treatment strategies in
      Langerhans cell histiocytosis (LCH) of the orbit. DESIGN: A perspective. METHODS:
      We reviewed the reported ophthalmic experience with unifocal LCH of the orbit,
      analyzed current oncologic clinical trial protocols, and provided a brief summary
      of contemporary knowledge and theory of LCH pathogenesis. RESULTS: Ophthalmic
      literature indicates that unifocal LCH of the orbit is usually responsive to
      local intervention. Current international oncologic protocols identify orbital
      LCH as a "central nervous system-risk" lesion (at risk for delayed-onset diabetes
      insipidus) and mandate a 6-month course of chemotherapy. Analysis suggests that
      the latter strategy is based on cases of orbital involvement in multifocal and
      multisystem disease. The pathologic Langerhans cell continues to define and unite
      the LCH variants, but cytokine activation of that cell may be an earlier
      pathogenetic determinant. Despite a common cellular mediator, LCH may be a
      heterogeneous process, with severity related to varied "upstream" trigger events.
      CONCLUSION: Treatment perspectives in LCH are influenced by dissimilar patient
      encounters and varied interpretations of the basic disease process. Pending
      documentation of linkage between unifocal orbital LCH and diabetes insipidus, we
      recommend local intervention, with systemic treatment reserved for incomplete
      response or local reactivation or the appearance of lesions elsewhere. LCH
      underscores the need for close interaction between specialists with intersecting
      clinical interests.

PMID- 16458700
TI  - Nimesulide oral administration increases the intraocular pressure-lowering effect
      of latanoprost in patients with primary open-angle glaucoma.
AB  - PURPOSE: To verify the short-term influence of an orally administered
      nonsteroidal anti-inflammatory drug on the intraocular pressure (IOP) of primary
      open-angle glaucoma patients in therapy with a topical prostaglandin analog.
      DESIGN: Randomized cross-over double-blind study. METHODS: Sixteen adults with
      primary open-angle glaucoma, receiving 0.005% latanoprost eyedrops once daily,
      were treated with a single dose of either 100 mg nimesulide or placebo. IOP was
      recorded at baseline and at 1, 2, 4, 8, 12, and 24 hours. RESULTS: After
      nimesulide administration, there was a decrease in IOP (with a fall at the second
      hour, P<.01) that remained significant 8 hours later (P<.05). At 12 and 24 hours,
      there were unremarkable IOP differences between the two regimens. CONCLUSIONS: In
      patients with primary open-angle glaucoma, single-dose nimesulide significantly
      enhances the latanoprost-induced IOP-lowering effects during the short plasma
      half-life of this non-steroidal anti-inflammatory drug.

PMID- 16458701
TI  - Intraocular rake for removal of epiretinal membranes.
AB  - PURPOSE: To examine the feasibility of the use of a flexible intraocular rake to
      remove epiretinal membranes (ERM). DESIGN: Interventional case series. METHODS: A
      multi-tine flexible intraocular rake was designed. Ten consecutive patients with
      idiopathic epiretinal membranes underwent vitrectomy and removal of the ERM with
      the intraocular rake. Outcome measures included intraoperative complications,
      Early Treatment Diabetic Retinopathy Study visual acuity, rate of recurrent ERM,
      and rate of persistent cystoid macular edema. RESULTS: The rake was used
      successfully to remove the ERM in all cases. Two patients had intraoperative
      retinal tears. At a mean postoperative follow-up examination of 24 weeks, the
      visual acuity was improved significantly (20/90 before the operation vs 20/50
      after the operation; P<.05). One patient had a recurrent epiretinal membrane.
      CONCLUSION: The flexible intraocular rake appears to be capable of the removal of
      idiopathic ERM. The increased tolerance for retinal contact that results from the
      flexible tines may make the rake of value to many vitreoretinal surgeons.

PMID- 16458702
TI  - Argon laser photoablation of conjunctival pigmented nevus.
AB  - PURPOSE: To evaluate the efficacy of an argon laser in the ablation of benign
      conjunctival pigmented nevi. DESIGN: Interventional case series. METHODS: We
      conducted argon laser ablations for conjunctival pigmented nevus in 30 eyes of 28
      patients. Laser ablation was applied directly to the conjunctival pigmented nevus
      in all patients. All patients were followed up over a period of 12 months.
      RESULTS: In all patients, the conjunctival lesions to which the argon laser was
      applied disappeared almost completely within two days after treatment. No
      recurrence of lesions was detected in any patient during the follow-up period,
      nor were any conjunctival scars or conjunctival injections. CONCLUSIONS: The
      argon-laser ablation of conjunctival pigmented nevi uniformaly resulted in
      excellent clinical outcomes. Therefore, this study concludes that argon laser
      ablation is a safe and effective modality for the treatment of benign
      conjunctival nevi, and this method could replace the classical surgical
      procedure.

PMID- 16458704
TI  - Fibrovascular ingrowth as a cause of Ahmed glaucoma valve failure in children.
AB  - PURPOSE: The purpose of this study is to document the presence of fibrovascular
      ingrowth into the Ahmed glaucoma valve (AGV) as a cause of AGV failure in the
      pediatric population. DESIGN: Retrospective case series. METHODS: Retrospective
      study of six children with histologically documented fibrovascular ingrowth of
      their AGV, with review of relevant demographic, clinical, and surgical factors.
      RESULTS: Six patients, two males and four females, with a mean age at AGV
      placement of 27.5 months (range 1 to 122) were identified with AGV failure, AGV
      removal, and subsequent histology documenting fibrovascular ingrowth into the
      valve chamber. Etiology of glaucoma included: trauma, aphakia, angle-closure,
      aniridia, and infantile. Mean time from AGV implantation to explantation was 23
      months (range 6 to 65). Mean intraocular pressure at AGV explantation was 35 mm
      Hg (range 27 to 48). CONCLUSIONS: Fibrovascular ingrowth of both the pediatric
      and adult size AGV occurs in children and should be considered in the presence of
      AGV failure.

PMID- 16458703
TI  - Clinical evaluation of the Smart Plug in the treatment of dry eyes.
AB  - PURPOSE: To evaluate the efficacy of a thermo sensitive punctum plug, the Smart
      Plug, in the treatment of dry eyes. DESIGN: Observational case-series study.
      METHODS: Eighteen eyes of 10 dry eye patients who previously failed conventional
      plug insertion were enrolled. Schirmer 1 test, vital staining scores, and tear
      clearance tests were performed before plug insertion, at 2 weeks, 1 month, and 3
      months after insertion. RESULTS: Although Schirmer test values were not
      significantly different before and after plug insertion, the tear clearance rate
      considerably decreased (Before insertion: 14.8+/-11.4; After insertion: 8.2+/
      6.6) (P<.05). Rose-Bengal and fluorescein scores improved significantly after
      plug insertion (Rose-Bengal: Before insertion: 6.4+/-2.0; After insertion: 3.3+/
      1.6 points, Fluorescein: Before insertion: 4.8+/-2.3; After insertion: 2.1+/-1.3)
      (P<.05). No complications were observed. CONCLUSIONS: Smart Plug proved to be a
      safe and efficient option in the treatment of dry eye.

PMID- 16458705
TI  - Clinical experience with the double-plate Ahmed glaucoma valve.
AB  - PURPOSE: To evaluate the clinical efficacy and safety of the double-plate Ahmed
      Glaucoma Valve. DESIGN: Multicenter, retrospective observational case series.
      METHODS: We reviewed 50 eyes in 50 patients treated with the double-plate Ahmed
      Glaucoma Valve with mean follow-up of 11.7+/-7.9 months. RESULTS: Average
      intraocular pressure was reduced from 36.0+/-12.4 mm Hg before surgery to 15.8+/
      7.7 mm Hg at the most recent follow-up after surgery (P<.001). The number of
      glaucoma medications was decreased from 3.3+/-0.8 before surgery to 1.4+/-1.4
      after surgery (P<.001). The percent of success was 76% of eyes at the latest
      follow-up. Choroidal effusion occurred in four eyes (8%) and did not require
      surgical treatment in any eye. CONCLUSIONS: Despite a poor prognosis group of
      patients in this study, the double-plate Ahmed Glaucoma Valve was effective in
      lowering intraocular pressure with a low incidence of complications associated
      with hypotony.

PMID- 16458706
TI  - Subretinal suture misdirection during 360 degrees suture trabeculotomy.
AB  - PURPOSE: To report a new complication of 360 degrees suture trabeculotomy
      attributable to subretinal suture misdirection. DESIGN: Observational case
      report. METHODS: Retrospective chart review. RESULTS: A 5-month-old female with
      bilateral congenital glaucoma underwent uncomplicated 360 degrees suture
      trabeculotomy in the right eye. In the left eye, a scleral flap was created and
      dissection to Schlemm's canal was achieved. A 6-0 Prolene suture was passed into
      Schlemm's canal long enough for 360 degrees of treatment, did not come out the
      opening, and was retracted. The procedure was completed with a trabeculotome. One
      month later, an unusual white tract was noted subretinally in the left eye. There
      was no overlying retinal break or detachment. The tract presumably was caused by
      the misdirected Prolene suture exiting Schlemm's canal prematurely and being
      directed posteriorly. CONCLUSIONS: Suture misdirection subretinally during
      cannulation of Schlemm's canal should be considered a possible complication of
      360 degrees suture trabeculotomy.

PMID- 16458707
TI  - Circumstance and outcome of ocular paintball injuries.
AB  - PURPOSE: To determine the circumstance and outcome of ocular injuries
      attributable to paintball projectiles. DESIGN: Retrospective interventional case
      series. METHODS: Institutional review board approved retrospective chart review
      of 19 consecutive eyes with paintball injuries with minimum follow-up of 3
      months. RESULTS: Ten eyes (53%) had final visual acuity of 20/40 or better, while
      seven (36%) were 20/200 or worse. Ten eyes were injured in paintball games, (two
      formal and eight informal), while nine (47%) were injured by accidents or
      assaults not associated with any "game." CONCLUSIONS: Paintball injuries often
      cause severe and permanent visual loss. Nearly half of these injuries occur
      outside a war game setting as accidents or assaults.

PMID- 16458708
TI  - Comparative study of cerebral blood flow in patients with normal-tension glaucoma
      and control subjects.
AB  - PURPOSE: To evaluate regional cerebral blood flow (rCBF) in normal-tension
      glaucoma patients (NTGs) compared with normal volunteers (controls) in a pilot
      study. DESIGN: Observational cohort study. METHODS: The Iodine-123-IMP single
      photon emission computed tomography (SPECT) scans were acquired in 31 NTGs and 18
      age-matched controls. The SPECT images in NTGs were classified and the
      quantitative rCBF data were compared with controls. RESULTS: Seven of 31 NTGs
      (22.6%) exhibited an Alzheimer's disease (AD)-like perfusion pattern although
      none of them were clinically diagnosed with AD. The visual field defect of NTGs
      with an AD-like pattern progressed more rapidly than NTGs with a normal pattern
      (P=.132). The rCBF in left parietal regions of NTGs with senile sclerotic or
      focal ischemic disk was significantly lower than controls (P<.05). CONCLUSIONS: A
      number of NTGs exhibited an AD-like perfusion pattern, suggesting that some of
      NTGs and AD patients might have a common pathologic mechanism.

PMID- 16458709
TI  - Retinal pigment epithelium tears following verteporfin therapy combined with
      intravitreal triamcinolone.
AB  - PURPOSE: To detect patients with neovascular age-related macular degeneration
      (AMD) who experience retinal pigment epithelium tears after initial verteporfin
      therapy combined with intravitreal triamcinolone during early follow-up. DESIGN:
      Prospective interventional case series. METHODS: Forty-five consecutive patients
      with choroidal neovascularization (CNV) in AMD were treated with verteporfin
      therapy combined with 4 mg of intravitreal triamcinolone. Optical coherence
      tomography (OCT), visual acuity, and fluorescein angiography were performed.
      RESULTS: Two eyes with a predominantly classic CNV developed a retinal pigment
      epithelium tear. An early onset tear could be differentiated from a delayed onset
      tear. OCT showed an increased depth signal in areas of missing retinal pigment
      epithelium and a wavy, contracted, and elevated retinal pigment epithelium band.
      CONCLUSIONS: Retinal pigment epithelium tears can occur despite adding
      intravitreal triamcinolone to verteporfin therapy. OCT shows characteristic
      changes in the evolution of retinal pigment epithelium tears after combination
      therapy.

PMID- 16458710
TI  - Bilateral visual loss in craniodiaphysial dysplasia.
AB  - PURPOSE: To report a rare case of craniodiaphysial dysplasia (CDD) that resulted
      in a profound loss of vision in both eyes. DESIGN: Observational case report.
      METHODS: A 2-year-old girl presented with midfacial anomaly. Marked thickening
      and sclerosis in the calvaria and facial bones were detected on the plain x-rays,
      which were compatible with CDD. Two years later, she visited our clinic because
      of visual loss in both eyes. RESULTS: The visual acuity was light perception in
      both eyes. The optic disk swelling with temporal pallor was observed in her both
      eyes. Orbital computed tomography scan revealed near-total obliteration of the
      optic canal in both eyes. CONCLUSIONS: CDD is a severe bone disorder
      characterized by massive generalized hyperostosis and sclerosis, especially
      involving the facial bones. Bony encroachment on the cranial foramina causes
      optic nerve compression, and this may lead to progressive visual impairment and
      ultimately to blindness.

PMID- 16458711
TI  - Ocular manifestation of cat-scratch disease in HIV-positive patients.
AB  - PURPOSE: To characterize ocular manifestations of cat-scratch disease in HIV
      positive patients. DESIGN: Retrospective case series study. METHODS: Records and
      photography of patients with the diagnosis of cat-scratch disease and HIV were
      reviewed. RESULTS: From 2001 and 2004 three patients with cat-scratch disease and
      HIV were identified. All patients presented with subretinal mass associated with
      an abnormal vascular network. Fluorescein angiography revealed this abnormal
      vascular network more clearly. All patients were treated with antibiotics alone
      with good response. CONCLUSIONS: Subretinal mass associated with abnormal
      vascular network is characteristic of cat-scratch disease in HIV-positive
      patients. Fluorescein angiography is important to characterize this vascular
      pattern, and patients may benefit from systemic treatment.

PMID- 16458713
TI  - Optical coherent tomography features of malattia leventinese.
AB  - PURPOSE: Malattia leventinese (ML) is an inherited macular degeneration
      characterized by the presence of large paracentral and small radial drusen. Our
      purpose was to describe optical coherent tomography (OCT) features observed in
      ML. DESIGN: Prospective observational case series. METHODS: Ten eyes from five
      patients with ML aged 27 to 44 years were prospectively included. Best-corrected
      visual acuity, fundus color photography of the retina, and OCT were performed in
      each patient. RESULTS: OCT revealed a hyperreflective thickening of the retinal
      pigment epithelium-Bruch membrane complex, associated with localized dome-shaped
      elevations. Retinal thickness above the drusen ranged from 221 to 292 microm
      (mean 260 microm). Foveal thickness ranged from 72 to 200 microm (mean 144
      microm) CONCLUSIONS: The large paracentral drusen presented either as a
      thickening of the retinal pigment epithelium-Bruch complex or as local limited
      elevation of retinal pigment epithelium-Bruch complex, both associated with
      preservation of the neurosensory retina.

PMID- 16458712
TI  - A myocilin Gln368STOP homozygote does not exhibit a more severe glaucoma
      phenotype than heterozygous cases.
AB  - PURPOSE: To describe the phenotype of an individual homozygous for the common
      Gln368STOP myocilin mutation and to discuss the other family members. DESIGN:
      Cascade screening was performed for Australian families that had been identified
      as having the myocilin Gln368STOP mutation. METHODS: Recruited subjects underwent
      comprehensive clinical examination and mutation analysis for the Gln368STOP
      myocilin mutation by direct sequencing. RESULTS: One 49-year-old woman was found
      to be homozygous for the mutation. Her maximal recorded intraocular pressure was
      17 mm Hg. Bilateral optic disk examination revealed small, healthy optic discs.
      Automated perimetry testing was normal. CONCLUSIONS: Neither the individual
      homozygous for the Gln368STOP myocilin mutation nor her younger heterozygous
      siblings displayed any signs suggestive of glaucoma. One of the two heterozygous
      parents did manifest glaucoma. Although there is the possibility of the
      homozygous individual developing glaucoma in the future, she does not manifest a
      phenotype that is more severe than usual.

PMID- 16458714
TI  - Subjective visual sensation during vitrectomy under retrobulbar anesthesia.
AB  - PURPOSE: To report a precise illustrated image of patient's view during
      vitrectomy. DESIGN: Interventional case report. METHODS: A 56-year-old male with
      cystoid macular edema (CME) associated with epiretinal membrane underwent
      vitrectomy. The patient seemed to find gratification in being operated on because
      he was able to see what was going on. He was a professional artist in computer
      graphics, and he drew three different pictures depending on the surgical
      procedures. RESULTS: These pictures depicted the moving of pasty, whirling fluid
      during core vitrectomy, numerous black or gray spots like snowflakes by
      intravitrealy injected crystals of triamcinolone acetonide, and a sharp tapered
      instrument coming into the center and membrane-like material being peeled off.
      CONCLUSIONS: Patients may see a precise shape in a constant size, scale, and
      detailed movement as well, focused on the retina without described optics.
      Further investigation will be required to determine this mechanism.

PMID- 16458715
TI  - Rapid progression of diabetic retinopathy in eyes with posterior uveitis.
AB  - PURPOSE: To report on two patients who developed rapid progression of asymmetric
      diabetic retinopathy (DRP) in eyes affected by posterior uveitis in contrast to
      their fellow eyes not affected by uveitis. DESIGN: Observational case report.
      METHODS: Two patients with diabetes mellitus (DM) and unilateral uveitis
      underwent repeated ophthalmologic examinations and fluorescein angiography.
      RESULTS: Two patients with DM and unilateral posterior uveitis developed
      proliferative DRP in eyes with previous uveitis within 3 months after the uveitis
      subsided. In contrast, the retinal findings of nonuveitic eyes remained unchanged
      on follow-up of several years. CONCLUSIONS: Since the pathogenesis of intraocular
      inflammation and diabetic retinopathy acts through similar biochemical mediators
      and pathways, it is feasible that posterior uveitis accelerates the progression
      of diabetic retinopathy. Our results support this hypothesis and point out a risk
      for rapid retinopathy development in eyes affected with posterior uveitis.

PMID- 16458716
TI  - Changes of corneal aberrations in sitting and supine positions.
AB  - PURPOSE: To examine the effect of posture change on corneal aberrations and
      corneal curvature. DESIGN: Observational case series. METHODS: The Keratron
      topographer, improved to measure patients in the supine position, was used to
      measure the corneal aberrations and the curvature in nine healthy volunteers. The
      first measurement took place with the subject in the sitting position and the
      others in the supine position, immediately after assuming the supine position and
      then 30 minutes later. RESULTS: The total higher-order and spherical-like
      aberrations were significantly increased from the sitting position to the supine
      position (P=.011, and P=.044, Scheffe test). CONCLUSIONS: These results suggest
      that the increase in the higher-order aberration from the sitting to the supine
      position acts to limit the improvements in visual performance after customized
      refractive surgery based on wavefront measurement.

PMID- 16458717
TI  - Reoperation for persistent myopic foveoschisis after primary vitrectomy.
AB  - PURPOSE: We performed vitrectomy on two eyes for persistent myopic foveoschisis
      (MF) after primary surgery that did not include internal limiting membrane (ILM)
      peeling. DESIGN: Interventional case reports. METHODS: Two highly myopic eyes of
      two patients with persistent MF after primary vitrectomy and gas tamponade but
      without ILM peeling were treated with pars plana vitrectomy, residual vitreous
      cortex removal, ILM peeling, and long-term gas tamponade. RESULTS: Total foveal
      reattachment was achieved and best-corrected visual acuity (BCVA) improved in
      both eyes. CONCLUSIONS: Reoperation including complete vitreous cortex removal
      and ILM peeling could be beneficial for patients with persistent MF after primary
      surgery, indicating that vitreous cortex removal and ILM peeling are critical in
      treating MF.

PMID- 16458718
TI  - Eisler and his pocket.
AB  - PURPOSE: To identify the original description of the anatomical structure
      referred to as "Eisler's pocket." DESIGN: Historical review. METHODS: Review of
      published reports. RESULTS: Contemporary reports cite a 1963 textbook by an
      American author as the source of the term "Eisler's pocket." The original
      description by Eisler appears in a multivolume manual of ophthalmology published
      in Germany in 1930. CONCLUSION: Paul Eisler was a skilled anatomist who
      contributed to the extensive body of scholarly work originating in Germany in the
      early 20th century.

PMID- 16458719
TI  - Evidence of genetic heterogeneity in MRCS (microcornea, rod-cone dystrophy,
      cataract, and posterior staphyloma) syndrome.
AB  - PURPOSE: To present the detailed phenotype of a subject with MRCS (microcornea,
      retinal dystrophy, cataract, and posterior staphyloma) syndrome and to
      investigate the underlying molecular genetic basis. DESIGN: Interventional case
      report. METHODS: Clinical examination, electrophysiologic assessment, B-scan
      ultrasonography, and mutation screening of the gene VMD2. The protocol of the
      study was approved by the local ethics committee and informed consent was
      obtained. RESULTS: A 12-year-old boy was identified with bilateral microcornea,
      rod-cone dystrophy, congenital cataracts, and posterior staphylomata associated
      with high myopia (MRCS). Mutation screening failed to identify disease-causing
      sequence variants in VMD2, the gene associated with MRCS syndrome. All previous
      subjects have had pathogenic VMD2 sequence alterations. CONCLUSIONS: We present a
      further report of the MRCS syndrome and provide evidence in support of genetic
      heterogeneity in this phenotype.

PMID- 16458721
TI  - Uveitis in Gaucher disease.

PMID- 16458726
TI  - Gastrointestinal complications of diabetes mellitus.

PMID- 16458724
TI  - Visual dysfunction after panretinal photocoagulation in patients with severe
      diabetic retinopathy and good vision.

PMID- 16458727
TI  - Esophageal cancer.

PMID- 16458729
TI  - Incremental lines in root cementum of human teeth--a reliable age marker?
AB  - In root cementum of teeth, alternating dark and light lines become visible in
      cross-sections under the light microscope. These lines bear an apparent
      resemblance to the annual rings of trees. Numerous studies have been done to
      correlate the number of cementum lines with the dental age by examining a great
      number of teeth of known age. Our study used a different approach. If lines in
      root cementum develop in an annual rhythm and are thus comparable to annual rings
      of trees, the same or at least a very similar number of these structures should
      be found in all areas of the root cementum of the same tooth. We counted cementum
      lines in the buccal, lingual, distal and mesial region of different sections, all
      from the middle third of the same root. This was repeated in eight teeth. To our
      surprise, we had immense difficulty in counting reproducible line numbers in the
      same cementum area at repeated counts. Nevertheless, the same tooth was found to
      differ markedly in the number of lines in different sections as well as in
      different regions of the same sections. These differences cannot be ascribed to
      variations caused by difficulties with reproducible line counting. Therefore, we
      are more than skeptical about the reliability of counting lines in root cementum
      as a method for determining the age of human teeth.

PMID- 16458728
TI  - Hyperostosis frontalis interna, a genetic disease?: Two medieval cases from
      Southern Poland.
AB  - Two cases of thickening of the internal tables of the frontal bones (hyperostosis
      frontalis interna, (HFI)) have been examined. These were two female skeletons
      from the 16th century Dominican Church in Raciborz (Southwest Poland). The
      similarity of their morphological and metrical traits indicates that they could
      be related, and suggests that HFI is likely to have a genetic base. These two
      skeletons are the subject of an analysis which may possibly throw some new light
      on the controversial and continually disputed nature of this illness.

PMID- 16458730
TI  - Acquisition of the lateral inconsistency in involuntary behaviour of upper limbs
      in 12-year-old children during walking at moderate speed.
AB  - The aim of this work was to investigate possible lateralisation in the behaviour
      of periodic motion of the human upper limb, during normal walking at a
      comfortable speed of locomotion. Ten healthy pre-adolescent, strongly right
      handed, 12-year-old males participated in the experiment. Participants were
      walking on a treadmill with a standardised velocity of 1.1m/s (comfortable speed
      for all of them). A video analysis system with Silicon software was used to
      synchronically measure various angles of arms and forearms. The initial, final
      and interim angular positions of both arms and forearms in 10 cycles of each
      participant were compared in terms of variations (cycle to cycle) between both
      upper extremities at corresponding phases of each cycle for distal and proximal
      segments, respectively. We compared the coefficients of variation in relation to
      the spatial and temporal data of both limbs and their angular velocities. In
      addition we investigated the level of cycle-to-cycle regularity (constancy) of
      behaviour in relation to various positions, periods and velocities of movement of
      upper extremities (specifically arms and forearms) using the Eta non-linear
      method of correlation. All participants exhibited a lower level of regularity for
      the distal segments. The spatial and temporal variations in the dominant limb
      were also greater than the non-dominant limb for all participants. This may be
      due to a larger contribution from the right-sided muscles that are considered to
      be the main contributing factor to the motion of the dominant upper limb during
      walking, rather than simply gravity force acting alone. A possible practical
      application of this information may be useful in the objective clinical
      identification of the level of dominance of the upper extremity (arm plus
      forearm), in addition to 'traditional' handedness.

PMID- 16458731
TI  - Adolescent growth in main somatometric traits of Japanese boys: Ogi Longitudinal
      Growth Study.
AB  - Considerable information is available on peak growth velocity characteristics of
      various body dimensions but the age at minimal velocity (AMV) and the duration of
      the spurt are not that well documented. Authors applied the mathematical growth
      model of Preece and Baines (PBGM1) to six longitudinally followed somatometric
      traits [height, sitting height, iliospinal height (B-ic), upper limb length (a
      da), biacromial diameter (a-a), and biiliocristal diameter (ic-ic)] of Japanese
      boys of Ogi Growth Study. Biological variables derived from the estimated
      parameters were studied with emphasis on duration and velocity characteristics of
      the adolescent spurt. Ages for measurements at peak velocities tend to be younger
      than previously reported non-Japanese ones. Spurt duration in limb measurements
      was significantly the shortest. Earlier AMV and later age at peak velocity (APV),
      thus the longest spurt duration, are the characteristic for transverse
      measurements (a-a, ic-ic). B-ic and a-da had the largest, while a-a and ic-ic had
      the smallest relative velocity at AMV. Another result for the transverse
      measurements is that the magnitudes of differences between relative minimal and
      peak velocities (RMV, RPV) are the largest. It is suggested that a high level of
      RMV results from early maturation of bones, thus leading to the shortest spurt
      duration in limb dimensions, while a low level of RMV results from late
      maturation of the bones, consequently leading to the longest spurt duration in
      transverse measurements. This tendency of reverse relation was present in the
      rest of the measurements as well. Transformation of velocity variables (minimal
      velocity -- MV, peak velocity -- PV) to relative ones, proved to be useful in
      observing the relation of spurts in measurements.

PMID- 16458733
TI  - The aging lower urinary tract.
AB  - PURPOSE: Age related changes in continence and the GU system, and how they affect
      the management of LUT dysfunction are discussed. Guidelines are offered regarding
      the diagnosis and management of incontinence in the elderly population. MATERIALS
      AND METHODS: Published literature and current treatment practice specific to
      elderly patients with LUT dysfunction were reviewed. RESULTS: LUT symptoms in the
      elderly population are affected by the high prevalence of comorbidity and
      polypharmacy. In addition, the GU system undergoes age related changes that
      increase the risk of LUT dysfunction. CONCLUSIONS: Incontinence in older persons
      is almost always caused by multiple factors, of which not all are directly
      related to the GU system. Issues such as polypharmacy, comorbidity, and the
      increased risk of medication side effects must be considered in planning
      treatment. The primary care physician and urologist or gynecologist should
      establish a partnership to co-manage the broad spectrum of factors affecting
      continence in elderly patients.

PMID- 16458734
TI  - Nocturia: "do the math".
AB  - PURPOSE: We reviewed the definition and etiologies of nocturia, offering the
      current diagnostic procedures and standards of care. MATERIALS AND METHODS: We
      reviewed recent published literature regarding nocturia, along with current
      paradigms for diagnosis and management. RESULTS: Nocturia is common as a limited
      occurrence but troublesome if the patient regularly experiences more than 2
      episodes during sleep hours. The 4 principle etiologies associated with nocturia
      (nocturnal polyuria, decreased nocturnal bladder capacity, mixed polyuria, and
      global polyuria) may be easily differentiated through mathematical analysis of a
      24-hour bladder diary. CONCLUSIONS: Nocturia is highly treatable in many
      patients. Identification of the precise type and its cause enable clinicians to
      minimize the inconvenience and sleep deprivation associated with nocturia.

PMID- 16458737
TI  - Erectile dysfunction.
AB  - PURPOSE: An overview of the latest concepts advanced with regard to the
      epidemiology, pathophysiology, and management of male ED is provided. MATERIALS
      AND METHODS: Published literature and current paradigms promoted by consensus
      bodies in the field with regard to the management of ED were reviewed. RESULTS:
      ED is a neurovascular phenomenon modulated by hormonal, local biochemical, and
      biomechanical/structural factors of the penis. Once viewed primarily as a
      psychological issue, ED is now understood to represent predominantly organic
      etiologies. It has a significant association with cardiovascular disease and
      could serve as a harbinger of subsequent cardiovascular events. Goal directed
      assessment and management implies a focus on patient (and partner) preferences
      regarding various treatment options. These options range from oral
      pharmacological agents to surgery and may be pursued according to a stepwise
      management approach. Psychosocial interventions also may serve as useful
      therapeutic adjuncts. CONCLUSIONS: ED is a highly manageable disorder in most
      patients. The patient and his partner have integral roles in the decision making
      process, since preferences regarding the importance of sexual activity, and the
      risks and benefits of treatment will vary greatly among individuals.

PMID- 16458735
TI  - Benign prostatic hyperplasia in primary care: what you need to know.
AB  - PURPOSE: We reviewed recent literature and treatment guidelines regarding the
      prevalence, pathophysiology, and management of BPO related to BPH; and management
      of lower urinary tract symptoms secondary to BPH. MATERIALS AND METHODS:
      Published literature and current treatment concepts were reviewed regarding the
      diagnosis and treatment options for BPO. RESULTS: BPH is a histological diagnosis
      that can contribute to medical problems, including enlargement of the prostate
      and BPO. These conditions should be treated only if the symptoms are troublesome,
      there is considerable risk of progression, and/or cancer is suspected. Very
      effective medical and surgical options are available to treat BPO and improve
      patient quality of life. CONCLUSIONS: BPO is highly treatable, but should be
      managed in close collaboration with the patient. Pharmacological agents and
      minimally invasive procedures, when appropriate, are generally preferred to more
      invasive surgery. Patients with mild or moderate symptoms usually can be treated
      by a primary care physician; more complicated cases should be referred to a
      urologist for evaluation and management.

PMID- 16458738
TI  - Current trends in lower urinary tract health highlights from annual advances in
      genitourinary health: a scientific update.

PMID- 16458740
TI  - Environmental influences on children's health.

PMID- 16458739
TI  - Overactive bladder: a better understanding of pathophysiology, diagnosis and
      management.
AB  - PURPOSE: We reviewed current information regarding the updated definitions,
      prevalence, etiologies, disease burden, and management of OAB from a number of
      perspectives, including professional impact and patient quality of life.
      MATERIALS AND METHODS: Published literature and current treatment concepts were
      reviewed regarding the understanding and management of OAB. RESULTS: OAB is a
      symptom syndrome including urinary urgency with or without urinary incontinence,
      usually with frequency and nocturia. Approximately 17% of the adult population
      experience OAB. There are evolving theories regarding its pathophysiology and the
      mechanism of action of the most commonly prescribed pharmacological therapy
      (antimuscarinic agents). Treatment primarily revolves around improving quality of
      life. CONCLUSIONS: Behavioral therapy combined with pharmacological therapy often
      will bring about acceptable outcomes for patients with OAB. Modalities such as
      botulinum toxin injections, neuromodulation, and various surgical interventions
      also are showing encouraging results in more refractory patients.

PMID- 16458741
TI  - Defending radiology.

PMID- 16458742
TI  - An ounce of prevention is better than the best trauma care.

PMID- 16458743
TI  - Changing the diagnostic framework of meningococcal disease.

PMID- 16458744
TI  - Statins: a preventive strike against sepsis in patients with cardiovascular
      disease?

PMID- 16458745
TI  - Communicating radiology results.

PMID- 16458746
TI  - Advanced-care practitioners--friend or foe?

PMID- 16458747
TI  - Medical education research at the crossroads.

PMID- 16458748
TI  - Psychosocial burden of infertility and assisted reproduction.

PMID- 16458749
TI  - Treatment of children with unexplained chronic pain.

PMID- 16458751
TI  - Retraction--Non-steroidal anti-inflammatory drugs and the risk of oral cancer: a
      nested case-control study.

PMID- 16458752
TI  - Autoimmune disease.

PMID- 16458753
TI  - Masood Umer.

PMID- 16458754
TI  - BCG and protection against Mycobacterium tuberculosis infection.

PMID- 16458755
TI  - Death from rheumatic heart disease in rural Ethiopia.

PMID- 16458756
TI  - BCG and protection against Mycobacterium tuberculosis infection.

PMID- 16458757
TI  - BCG and protection against Mycobacterium tuberculosis infection.

PMID- 16458759
TI  - Accelerated measles control in sub-Saharan Africa.

PMID- 16458760
TI  - Trachoma research: it takes more than a village.

PMID- 16458761
TI  - Antiretroviral drugs are running out in Zimbabwe.

PMID- 16458762
TI  - Could 3 by 5 increase HIV transmission?

PMID- 16458763
TI  - Clinical recognition of meningococcal disease in children and adolescents.
AB  - BACKGROUND: Meningococcal disease is a rapidly progressive childhood infection of
      global importance. To our knowledge, no systematic quantitative research exists
      into the occurrence of symptoms before admission to hospital. METHODS: Data were
      obtained from questionnaires answered by parents and from primary-care records
      for the course of illness before admission to hospital in 448 children (103
      fatal, 345 non-fatal), aged 16 years or younger, with meningococcal disease. In
      373 cases, diagnosis was confirmed with microbiological techniques. The rest of
      the children were included because they had a purpuric rash, and either
      meningitis or evidence of septicaemic shock. Results were standardised to UK case
      fatality rates. FINDINGS: The time-window for clinical diagnosis was narrow. Most
      children had only non-specific symptoms in the first 4-6 h, but were close to
      death by 24 h. Only 165 (51%) children were sent to hospital after the first
      consultation. The classic features of haemorrhagic rash, meningism, and impaired
      consciousness developed late (median onset 13-22 h). By contrast, 72% of children
      had early symptoms of sepsis (leg pains, cold hands and feet, abnormal skin
      colour) that first developed at a median time of 8 h, much earlier than the
      median time to hospital admission of 19 h. INTERPRETATION: Classic clinical
      features of meningococcal disease appear late in the illness. Recognising early
      symptoms of sepsis could increase the proportion of children identified by
      primary-care clinicians and shorten the time to hospital admission. The framework
      within which meningococcal disease is diagnosed should be changed to emphasise
      identification of these early symptoms by parents and clinicians.

PMID- 16458764
TI  - Self-monitoring of oral anticoagulation: a systematic review and meta-analysis.
AB  - BACKGROUND: Near-patient testing has made self-monitoring of anticoagulation with
      warfarin feasible, and several trials have suggested that such monitoring might
      be equal to or better than standard monitoring. We did a systematic review and
      meta-analysis of all randomised controlled trials that assessed the effects of
      self-monitoring or self-management (self-testing and self-dosage) of
      anticoagulation compared with standard monitoring. METHODS: We searched the
      Cochrane Register of Controlled Trials, MEDLINE, EMBASE to April 2005, and
      contacted manufacturers and authors of relevant studies. Outcomes analysed were:
      major haemorrhage, thromboembolic events, death, tests in range, minor
      haemorrhage, frequency of testing, and feasibility of self-monitoring. FINDINGS:
      We identified 14 randomised trials of self-monitoring: pooled estimates showed
      significant reductions in thromboembolic events (odds ratio 0.45, 95% CI 0.30
      0.68), all-cause mortality (0.61, 0.38-0.98), and major haemorrhage (0.65, 0.42
      0.99). Trials of combined self-monitoring and self-adjusted therapy showed
      significant reductions in thromboembolic events (0.27, 0.12-0.59) and death
      (0.37, 0.16-0.85), but not major haemorrhage (0.93, 0.42-2.05). No difference was
      noted in minor haemorrhage. 11 trials reported improvements in the mean
      proportion of international normalisation ratios in range. INTERPRETATION: Self
      management improves the quality of oral anticoagulation. Patients capable of self
      monitoring and self-adjusting therapy have fewer thromboembolic events and lower
      mortality than those who self-monitor alone. However, self-monitoring is not
      feasible for all patients, and requires identification and education of suitable
      candidates.

PMID- 16458765
TI  - Self-monitoring of oral anticoagulation.

PMID- 16458766
TI  - Statins and sepsis in patients with cardiovascular disease: a population-based
      cohort analysis.
AB  - BACKGROUND: Atherosclerosis and sepsis share several pathophysiological
      similarities, including immune dysregulation, increased thrombogenesis, and
      systemic inflammation. The relation between statins and risk of sepsis in
      patients with atherosclerosis is unknown. METHODS: We did a population-based
      cohort analysis through linked administrative databases in Ontario, Canada, with
      accrual from 1997 to 2002. We identified 141,487 patients older than 65 years who
      had been hospitalised for an acute coronary syndrome, ischaemic stroke, or
      revascularisation, who survived for at least 3 months after discharge. 46,662
      (33%) were prescribed a statin within 90 days of discharge, 94,825 (67%) were
      not. Propensity-based matching, which accounted for each individual's likelihood
      of receiving a statin, yielded a cohort of 69,168 patients, of whom half (34,584)
      received a statin and half (34,584) did not. FINDINGS: Incidence of sepsis was
      lower in patients receiving statins than in controls (71.2 vs 88.0 events per
      10,000 person-years; hazard ratio [HR] 0.81; 95% CI 0.72-0.91). Adjustment for
      demographic characteristics, sepsis risk factors, comorbidities, and health-care
      use gave similar results (HR 0.81; 95% CI 0.72-0.90). The protective association
      between statins and sepsis persisted in high-risk subgroups, including patients
      with diabetes mellitus, chronic renal failure, or a history of infections.
      Significant reductions in severe sepsis (HR 0.83; 95% CI 0.70-0.97) and fatal
      sepsis (0.75; 0.61-0.93) were also observed. No benefit was noted with non-statin
      lipid-lowering agents (0.95; 0.75-1.22). IMPLICATIONS: Use of statins in patients
      with atherosclerosis is associated with a reduced risk of subsequent sepsis.
      Randomised trials of statins for prevention of sepsis are warranted.

PMID- 16458767
TI  - Identification of a new Neisseria meningitidis serogroup C clone from Anhui
      province, China.
AB  - BACKGROUND: Outbreaks of a new serogroup C meningococcal disease emerged during
      2003-04 (five outbreaks with 43 cases) and in 2004-05 (five outbreaks with 29
      cases), all in Anhui province, China. We describe the molecular epidemiology and
      features of the causative bacterial strains. METHODS: We used pulsed-field gel
      electrophoresis (PFGE) and multi-locus sequence typing (MLST) to analyse the
      strains. FINDINGS: Of 34 strains of Neisseria meningitidis cultured during 2003
      04 from Anhui province, 31 were group C meningococci, 28 of which were associated
      with three of five outbreaks; one from a patient and 27 from close contacts of
      eight patients. Of 30 strains isolated from Anhui province during 2004-05, 17
      were identified as serogroup C meningococci, ten of which were associated with
      four of five outbreaks. In a nationwide survey, 542 strains were isolated during
      2004-05; 58 were serogroup C meningococci interspersed among 11 other provinces
      where no serogroup C outbreak occurred. Of the 106 serogroup C strains analysed,
      89 had identical PFGE patterns, designated AH1. Of 28 strains selected for MLST
      analyses, 25 were sequence type 4821 (ST-4821), which did not belong to any of
      the previously reported sequence types that can form a new hypervirulent lineage.
      INTERPRETATION: ST-4821 seems to be unique and caused the serogroup C meningitis
      outbreaks during the two seasons from 2003 to 2005 in Anhui province. The
      emergence of this sequence type has epidemiological importance that should be
      monitored for future spread in China and the rest of the world.

PMID- 16458768
TI  - Intra-cavity right ventricular metastasis.

PMID- 16458769
TI  - Smallpox.
AB  - The WHO declared smallpox eradicated in 1980. However, concern over its potential
      use by terrorists or in biowarfare has led to striking growth in research related
      to this much-feared disease. Modern molecular techniques and new animal models
      are advancing our understanding of smallpox and its interaction with the host
      immune system. Rapid progress is likewise being made in smallpox laboratory
      diagnostics, smallpox vaccines, and antiviral medications. WHO and several
      nations are developing stockpiles of smallpox vaccine for use in the event the
      disease is reintroduced. National and international public-health agencies have
      also drawn up plans to help with early detection of and response to a smallpox
      outbreak. These plans hinge on physicians' ability to recognise the clinical
      features of smallpox and to distinguish it from other illnesses characterised by
      rashes.

PMID- 16458770
TI  - Compulsory vaccination and conscientious or philosophical exemptions: past,
      present, and future.
AB  - Compulsory vaccination has contributed to the success of immunisation programmes
      in the USA and Australia, yet the benefits from compulsory vaccination are not
      universally recognised. Some people--experts and the public alike--believe that
      the benefits of compulsory vaccination are outweighed by the associated ethical
      problems. A review of vaccination legislation in the UK, Australia, and the USA
      raises four main points. First, compulsory vaccination may be effective in
      preventing disease outbreaks, reaching and sustaining high immunisation coverage
      rates, and expediting the introduction of new vaccines. Second, to be effective,
      compulsory programmes must have a reliable supply of safe and effective vaccines
      and most people must be willing to be vaccinated. Third, allowance of exemptions
      to compulsory vaccination may limit public backlash. Finally, compulsory
      vaccination may increase the burden on governments to ensure the safety of
      vaccines. Nevertheless, although compulsory immunisation can be very effective,
      it might not be acceptable in some countries where high coverage has been
      achieved through other approaches or efforts, such as in Sweden, Norway, Denmark,
      the Netherlands, and the UK. These factors should be considered when compulsory
      vaccinations are being introduced or immunisation laws refined. Lessons learned
      from compulsory vaccination could be useful to other public-health programmes.

PMID- 16458771
TI  - Radiology reporting--where does the radiologist's duty end?

PMID- 16458772
TI  - Unexpected shortness of breath in a patient with Cushing's syndrome.

PMID- 16458773
TI  - Osteoradionecrosis prevention myths.
AB  - PURPOSE: To critically analyze controversial osteoradionecrosis (ORN) prevention
      techniques, including preradiation extractions of healthy or restorable teeth and
      the use of prophylactic antibiotics or hyperbaric oxygen (HBO) treatments for
      preradiation and postradiation extractions. METHODS: The author reviewed ORN
      studies found on PubMed and in other article references, including studies on
      overall ORN incidence and pre- and postradiation incidence, with and without
      prophylactic HBO or antibiotics. RESULTS: Owing in part to more efficient
      radiation techniques, the incidence of ORN has been declining in radiation
      patients over the last 2 decades, but the prevention of ORN remains
      controversial. A review of the available literature does not support the
      preradiation extraction of restorable or healthy teeth. There is also
      insufficient evidence to support the use of prophylactic HBO treatments or
      prophylactic antibiotics before extractions or other oral surgical procedures in
      radiation patients. CONCLUSIONS: To prevent ORN, irradiated dental patients
      should maintain a high level of oral health. A preradiation referral for a dental
      evaluation and close collaboration by a multidisciplinary team can be invaluable
      for radiation patients. As with most other dental patients, restorable and
      healthy teeth should be retained in irradiated patients. The use of prophylactic
      HBO or antibiotics should be reconsidered for preradiation and postradiation
      extractions.

PMID- 16458774
TI  - Reproducibility of liver position using active breathing coordinator for liver
      cancer radiotherapy.
AB  - PURPOSE: To measure the intrabreath-hold liver motion and the intrafraction and
      interfraction reproducibility of liver position relative to vertebral bodies
      using an active breathing coordinator (ABC) in patients with unresectable liver
      cancer treated with hypofractionated stereotactic body radiation therapy (SBRT).
      METHODS: Tolerability of ABC and organ motion during ABC was assessed using kV
      fluoroscopy in 34 patients. For patients treated with ABC, repeat breath-hold CT
      scans in the ABC breath-hold position were acquired at simulation to estimate the
      volumetric intrafraction reproducibility of the liver relative to the vertebral
      bodies. In addition, preceding each radiation therapy fraction, with the liver
      immobilized using ABC, repeat anteroposterior (AP) megavoltage verification
      images were obtained. Off-line alignments were completed to determine
      intrafraction reproducibility (from repeat images obtained before one treatment)
      and interfraction reproducibility (from comparisons of the final image for each
      fraction with the AP) of diaphragm position relative to vertebral bodies. For
      each image set, the vertebral bodies were aligned, and the resultant craniocaudal
      (CC) offset in diaphragm position was measured. Liver position during ABC was
      also evaluated from kV fluoroscopy acquired at the time of simulation, kV
      fluoroscopy at the time of treatment, and from MV beam's-eye view movie loops
      acquired during treatment. RESULTS: Twenty-one of 34 patients were screened to be
      suitable for ABC. The average free breathing range of these patients was 13 mm
      (range, 5-1 mm). Fluoroscopy revealed that the average maximal diaphragm motion
      during ABC breath-hold was 1.4 mm (range, 0-3.4 mm). The MV treatment movie loops
      confirmed diaphragm stability during treatment. For a measure of intrafraction
      reproducibility, an analysis of 36 repeat ABC computed tomography (CT) scans in
      14 patients was conducted. The average mean difference in the liver surface
      position was -0.9 mm, -0.5 mm, and 0.2 mm in the CC, AP, and medial-lateral (ML)
      directions, with a standard deviation of 1.5 mm, 1.5 mm, and 1.5 mm,
      respectively. Ninety-five percent of the liver surface had an absolute
      differences in position between repeat ABC CT scans of less than 4.1 mm, 3.3 mm,
      and 3.3 mm in the CC, AP, and ML directions, respectively. Analysis of 257 MV AP
      images from patients treated using ABC revealed an average intrafraction CC
      reproducibility (sigma) of diaphragm relative to vertebral bodies of 1.5 mm
      (range, 0.6-3.9 mm). The average interfraction CC reproducibility (sigma) was 3.4
      mm (range, 1.5-7.9 mm), indicating less day-to-day reproducibility of diaphragm
      position relative to vertebral bodies. The average absolute intra and
      interfraction CC offset in diaphragm position relative to vertebral bodies was
      1.7 and 3.7 mm, respectively, with 86% of intrafraction and 54% of interfraction
      absolute offsets 3.0 mm or less. CONCLUSIONS: Intrafraction reproducibility of
      liver position using ABC is good in the majority of screened patients. However,
      interfraction reproducibility is worse, suggesting a need for image guidance.

PMID- 16458775
TI  - Decline in urinary retention incidence in 805 patients after prostate
      brachytherapy: the effect of learning curve?
AB  - PURPOSE: To evaluate the incidence and factors predictive of acute urinary
      retention (AUR) in 805 consecutive patients treated with prostate brachytherapy
      monotherapy and to examine the possible effect of a learning curve. METHODS AND
      MATERIALS: Between July 1998 and November 2002, 805 patients were treated with
      prostate brachytherapy. Low-risk patients (Gleason Score (GS) < or = 6; prostate
      specific antigen (PSA) < or = 10, and < or = T2b [UICC 1997]) received implant
      alone. Patients with prostate volume of 50 cc or more, GS = 7, or PSA = 10 to 15
      received 6 months of androgen suppression (AS) with brachytherapy. Patient,
      treatment, and dosimetric factors examined include baseline prostate symptom
      score (IPSS), diabetes, vascular disease, PSA, Gleason score, clinical stage, AS,
      ultrasound planning target volume (PUTV), postimplant prostate volume (obtained
      with "Day 30" postimplant CT), CT:PUTV ratio (surrogate for postimplant edema),
      number of seeds, number of needles, number of seeds per needle, dosimetric
      parameters (V100, V150, and D90), date of implant (learning curve), and
      implanting oncologists. Univariate and multivariate analyses were carried out.
      RESULTS: Acute urinary retention in the first 200 patients was 17% vs. 6.3% in
      the most recently treated 200 patients (p = 0.002). Overall AUR was 12.7%, and
      prolonged urinary obstruction incidence (> 20 days) was 5%. On multivariate
      analysis, factors predictive of any AUR include baseline IPSS (p = < 0.004),
      CT:PUTV ratio (p = < 0.001), PUTV (p = < 0.001), and implant order (learning
      curve) (p = 0.001). Factors predictive for "prolonged" catheterization (> 20
      days) on multivariate analysis include IPSS (p < 0.01), number of needles (p <
      0.001), diabetes mellitus (p = 0.048), and CT:PUTV ratio (p < 0.001) CONCLUSION:
      Over the years, our AUR rate has fallen significantly (from 17% to 6.3%). On
      multivariate analysis, highly significant factors include IPSS, PUTV, CT:PUTV
      ratio (i.e., degree of prostate edema), and order of implant (learning curve).
      Over the course of the program, we have deliberately reduced the number of
      needles and OR time per patient, which have potentially minimized intraoperative
      trauma and may have contributed to less toxicity. A learning curve in prostate
      brachytherapy programs affect not only the outcome but also the toxicity from the
      treatment.

PMID- 16458776
TI  - Adaptive radiotherapy for invasive bladder cancer: a feasibility study.
AB  - PURPOSE: To evaluate the feasibility of adaptive radiotherapy (ART) in
      combination with a partial bladder irradiation. METHODS AND MATERIALS: Twenty-one
      patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder
      tumor + 2 cm margin planning target volume (PTV(CONV)). During the first
      treatment week, five daily computed tomography (CT) scans were made immediately
      before or after treatment. In the second week, a volume was constructed
      encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT
      scans (GTV(ART)). The GTV(ART) was expanded with a 1 cm margin for the
      construction of a PTV(ART). Starting in the third week, patients were treated to
      PTV(ART). Repeat CT scans were used to evaluate treatment accuracy. RESULTS: On 5
      of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV(ART).
      On treatment planning, there was only one scan in which the GTV was not
      adequately covered by the 95% isodose. On average, the treatment volumes were
      reduced by 40% when comparing PTV(ART) with PTV(CONV) (p < 0.0001). CONCLUSION:
      The adaptive strategy for bladder cancer is an effective way to deal with
      treatment errors caused by variations in bladder tumor position and leads to a
      substantial reduction in treatment volumes.

PMID- 16458777
TI  - Intensity-modulated radiotherapy in high-grade gliomas: clinical and dosimetric
      results.
AB  - PURPOSE: To report preliminary clinical and dosimetric data from intensity
      modulated radiotherapy (IMRT) for malignant gliomas. METHODS AND MATERIALS: Fifty
      eight consecutive high-grade gliomas were treated between January 2001 and
      December 2003 with dynamic multileaf collimator IMRT, planned with the inverse
      approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total
      of three to five noncoplanar beams were used to cover at least 95% of the target
      volume with the prescription isodose line. Glioblastoma accounted for 70% of the
      cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15%
      of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80%
      received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months,
      85% of the patients have relapsed. The median progression-free survival time for
      anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months,
      respectively. The overall survival time for anaplastic glioma and glioblastoma
      was 36 and 9 months, respectively. Ninety-six percent of the recurrences were
      local. No Grade IV/V late neurologic toxicities were noted. A comparative
      dosimetric analysis revealed that regardless of tumor location, IMRT did not
      significantly improve target coverage compared with three-dimensional planning.
      However, IMRT resulted in a decreased maximum dose to the spinal cord, optic
      nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose
      conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated
      radiotherapy delivered with a limited number of beams did not result in an
      increased dose to the normal brain. CONCLUSIONS: It is unlikely that IMRT will
      improve local control in high-grade gliomas without further dose escalation
      compared with conventional radiotherapy. However, it might result in decreased
      late toxicities associated with radiotherapy.

PMID- 16458778
TI  - EF5 binding and clinical outcome in human soft tissue sarcomas.
AB  - PURPOSE: To study the 2-nitroimidazole agent EF5 as a surrogate for measuring
      hypoxia in a series of patients with soft tissue sarcomas, and to determine
      whether hypoxia measured with this technique was associated with patient outcome.
      METHODS AND MATERIALS: Patients with soft tissue sarcomas of the head and neck,
      extremity, trunk, or retroperitoneum for whom surgical excision was the initial
      treatment of choice, were given 21 mg/kg EF5 24-48 hours before surgery. Biopsy
      specimens were stained for EF5 binding with fluorescence-labeled monoclonal
      antibodies, and the images were analyzed quantitatively. Endpoints included the
      relationship between EF5 binding, clinically important prognostic factors, and
      patient outcome. RESULTS: Two patients with recurrent and 14 patients with de
      novo sarcomas were studied. There were seven low-grade, one intermediate-grade,
      and eight high-grade tumors. No relationship was found between EF5 binding and
      patient age, sex, hemoglobin level, or tumor size. In de novo tumors, the
      presence of mitoses and histologic grade were positively correlated with hypoxia.
      High-grade and -stage de novo tumors had higher levels of EF5 binding compared
      with low-grade and -stage tumors. Patients with de novo tumors containing
      moderate to severe hypoxia (> or = 20% EF5 binding), high grade, or > or = 7%
      mitoses were more likely to develop metastases. CONCLUSIONS: Further studies in a
      larger cohort of patients are necessary to determine whether hypoxia, as measured
      by EF5 binding, is an independent prognostic factor for outcome in high-grade
      sarcomas. Such data should be useful to identify high-risk patients for clinical
      trials to determine whether early chemotherapy will influence the occurrence of
      metastasis.

PMID- 16458779
TI  - Linear quadratic modeling of increased late normal-tissue effects in special
      clinical situations.
AB  - PURPOSE: To extend linear quadratic theory to allow changes in normal-tissue
      radiation tolerance after exposure to cytotoxic chemotherapy, after surgery, and
      in elderly patients. METHODS: Examples of these situations are analyzed by use of
      the biologic effective dose (BED) concept. Changes in tolerance can be allowed
      for by: estimation of either the contribution of the additional factor as an
      equivalent BED or the equivalent dose in 2-Gy fractions or by the degree of
      radiosensitization by a mean dose-modifying factor (x). RESULTS: The estimated x
      value is 1.063 (95% confidence limits for the mean, 1.056 to 1.070) for
      subcutaneous fibrosis after cyclophosphamide, methotrexate, and fluorouracil
      (CMF) chemotherapy and radiotherapy in breast cancer. The point estimate of x is
      1.18 for the additional risk of gastrointestinal late-radiation effects after
      abdominal surgery in lymphoma patients (or 10.62 Gy at 2 Gy per fraction). For
      shoulder fibrosis in patients older than 60 years after breast and nodal
      irradiation, x is estimated to be 1.033 (95% confidence limits for the mean,
      1.028 to 1.0385). The equivalent BED values were CMF chemotherapy (6.48 Gy3),
      surgery (17.73 Gy3), and age (3.61 Gy3). CONCLUSIONS: The LQ model can, in
      principle, be extended to quantify reduced normal-tissue tolerance in special
      clinical situations.

PMID- 16458780
TI  - Color intensity projections: a rapid approach for evaluating four-dimensional CT
      scans in treatment planning.
AB  - PURPOSE: Four-dimensional computerized tomography scans (4DCT) enable
      intrafractional motion to be determined. Because more than 1500 images can be
      generated with each 4DCT study, tools for efficient data visualization and
      evaluation are needed. We describe the use of color intensity projections (CIP)
      for visualizing mobility. METHODS: Four-dimensional computerized tomography
      images of each patient slice were combined into a CIP composite image. Pixels
      largely unchanged over the component images appear unchanged in the CIP image.
      However, pixels whose intensity changes over the phases of the 4DCT appear in the
      CIP image as colored pixels, and the hue encodes the percentage of time the
      tissue was in each location. CIPs of 18 patients were used to study tumor and
      surrogate markers, namely the diaphragm and an abdominal marker block. RESULTS:
      Color intensity projections permitted mobility of high-contrast features to be
      quickly visualized and measured. In three selected expiratory phases ("gating
      phases") that were reviewed in the sagittal plane, gating would have reduced mean
      tumor mobility from 6.3 +/- 2.0 mm to 1.4 +/- 0.5 mm. Residual tumor mobility in
      gating phases better correlated with residual mobility of the marker block than
      that of the diaphragm. CONCLUSION: CIPs permit immediate visualization of
      mobility in 4DCT images and simplify the selection of appropriate surrogates for
      gated radiotherapy.

PMID- 16458781
TI  - Integral radiation dose to normal structures with conformal external beam
      radiation.
AB  - BACKGROUND: This study was designed to evaluate the integral dose (ID) received
      by normal tissue from intensity-modulated radiotherapy (IMRT) for prostate
      cancer. METHODS AND MATERIALS: Twenty-five radiation treatment plans including
      IMRT using a conventional linac with both 6 MV (6MV-IMRT) and 20 MV (20MV-IMRT),
      as well as three-dimensional conformal radiotherapy (3DCRT) using 6 MV (6MV
      3DCRT) and 20 MV (20MV-3DCRT) and IMRT using tomotherapy (6MV) (Tomo-IMRT), were
      created for 5 patients with localized prostate cancer. The ID (mean dose x tissue
      volume) received by normal tissue (NTID) was calculated from dose-volume
      histograms. RESULTS: The 6MV-IMRT resulted in 5.0% lower NTID than 6MV-3DCRT; 20
      MV beam plans resulted in 7.7%-11.2% lower NTID than 6MV-3DCRT. Tomo-IMRT NTID
      was comparable to 6MV-IMRT. Compared with 6MV-3DCRT, 6MV-IMRT reduced IDs to the
      rectal wall and penile bulb by 6.1% and 2.7%, respectively. Tomo-IMRT further
      reduced these IDs by 11.9% and 16.5%, respectively. The 20 MV did not reduce IDs
      to those structures. CONCLUSIONS: The difference in NTID between 3DCRT and IMRT
      is small. The 20 MV plans somewhat reduced NTID compared with 6 MV plans. The
      advantage of tomotherapy over conventional IMRT and 3DCRT for localized prostate
      cancer was demonstrated in regard to dose sparing of rectal wall and penile bulb
      while slightly decreasing NTID as compared with 6MV-3DCRT.

PMID- 16458782
TI  - Monte Carlo-based dosimetry of head-and-neck patients treated with SIB-IMRT.
AB  - PURPOSE: To evaluate the accuracy of previously reported
      superposition/convolution (SC) dosimetric results by comparing with Monte Carlo
      (MC) dose calculations for head-and-neck intensity-modulated radiation therapy
      (IMRT) patients treated with the simultaneous integrated boost technique. METHODS
      AND MATERIALS: Thirty-one plans from 24 patients previously treated on a phase
      I/II head-and-neck squamous cell carcinoma simultaneous integrated boost IMRT
      protocol were used. Clinical dose distributions, computed with an SC algorithm,
      were recomputed using an EGS4-based MC algorithm. Phantom-based dosimetry
      quantified the fluence prediction accuracy of each algorithm. Dose-volume indices
      were used to compare patient dose distributions. RESULTS AND DISCUSSION: The MC
      algorithm predicts flat-phantom measurements better than the SC algorithm.
      Average patient dose indices agreed within 2.5% of the local dose for targets;
      5.0% for parotids; and 1.9% for cord and brainstem. However, only 1 of 31 plans
      agreed within 3% for all indices; 4 of 31 agreed within 5%. In terms of the
      prescription dose, 4 of 31 plans agreed within 3% for all indices, whereas 28 of
      31 agreed within 5%. CONCLUSIONS: Average SC-computed doses agreed with MC
      results in the patient geometry; however deviations >5% were common. The fluence
      modulation prediction is likely the major source of the dose discrepancy. The
      observed dose deviations can impact dose escalation protocols, because they would
      result in shifting patients to higher dose levels.

PMID- 16458783
TI  - An introduction to prostate cancer and geographic information systems.

PMID- 16458784
TI  - Geographically based investigation of prostate cancer mortality in four U.S.
      Northern Plain states.
AB  - BACKGROUND: Historically, prostate cancer mortality rates have been elevated in
      the U.S. Northern Plains states. The purpose of this study was to investigate
      possible contributing factors, especially whether there was any association with
      crop patterns. METHODS: Prostate cancer mortality rates (1950-2000) in four
      northern plains states (MN, MT, ND, and SD) were compared to rates for 46 other
      U.S. states. Within the four states, county rates in urban, less urban, and rural
      areas also were compared. For additional analysis, urban counties and counties
      with <10% of county area in crops were excluded. The average percent of county
      area in total cropland 1930-1950 and 1954-1974 was estimated. Using Poisson
      regression, we investigated whether the average percentage of county area in
      total cropland, 1930-1950 and 1954-1974, was associated with prostate cancer
      mortality rates, 1975-2000, respectively. Poisson regression analyses were also
      used to evaluate associations between rates and major crops, which included
      spring and durum wheat, winter wheat, corn, and other crops. Population centroids
      of the Census 2000 block groups were used to estimate the percentage of males
      aged 35 and older residing in close proximity to small grains crops. RESULTS:
      Mortality rates were higher in rural compared to urban counties in 1950-2000
      (rate ratio [RR]=1.032; 95% CI=1.001-1.063). Rates in 1950-1974 were
      significantly associated with production of corn and other crops in 1930-1950
      (corn: RR per 10% increase=1.033, 95% CI=1.012-1.054; other crops: RR=1.042, 95%
      CI=1.021-1.063). Mortality rates in 1975-2000 were significantly associated with
      spring and durum wheat production in 1954-1974 (RR per 10% increase=1.042, 95%
      CI=1.017-1.067). Prostate cancer mortality rates increased as the percentage of
      population living within 500 m of small grains crops increased. CONCLUSIONS:
      Epidemiologic studies to evaluate agricultural practices are warranted to further
      evaluate the observed associations.

PMID- 16458785
TI  - Control selection and pesticide exposure assessment via GIS in prostate cancer
      studies.
AB  - BACKGROUND: Pesticide exposures have recently been linked to prostate cancer, but
      accurate exposure assessment to date has been challenging. Additionally,
      historical exposures have rarely been examined. The utility of a geographic
      information system (GIS)-based model for assessing residential exposure to
      pesticides is examined in a population-based case-control setting among groups
      easily recruited as control subjects. METHODS: Historical pesticide and land-use
      data were used to generate exposure measures for two distinct pesticides
      previously linked to prostate cancer risk for control series and prostate cancer
      cases in three rural California counties. Simple estimates of residential
      exposures for different exposure periods are compared between case and control
      groups and the value of complete residential histories is examined. RESULTS:
      Residential exposure to methyl bromide based on current address resulted in an
      overestimation of exposure for distant exposure periods, whereas exposures to
      organochlorines were similar regardless of availability of historical residence
      information. A response bias was detected in Medicare controls such that
      unexposed elderly control subjects were characterized by a higher response rate.
      CONCLUSIONS: The frequency and amount of application of pesticides seem to affect
      the bias introduced into GIS-based exposure assessments. Inclusion of subjects'
      complete residential histories into the computation of exposure estimates seems
      to reduce bias from this source, but it may also introduce an additional bias
      through control self-selection. The use of randomly sampled controls from
      Medicare and residential parcels listings independent of subject response seems
      to result in the opportunity for relatively unbiased estimates of pesticide
      exposures.

PMID- 16458786
TI  - Geocoding in cancer research: a review.
AB  - There is now widespread agreement that geographic identifiers (geocodes) should
      be assigned to cancer records, but little agreement on their form and how they
      should be assigned, reported, and used. This paper reviews geocoding practice in
      relation to major purposes and discusses methods to improve the accuracy of
      geocoded cancer data. Differences in geocoding methods and materials introduce
      errors of commission and omission into geocoded data. A common source of error
      comes from the practice of using digital boundary files of dubious quality to
      place addresses into areas of interest. Geocoded data are linked to demographic,
      environmental, and health services data, and each data type has unique accuracy
      considerations. In health services applications, the accuracy of distances
      computed from geocodes can differ markedly. Privacy and confidentiality issues
      are important in the use and release of geocoded cancer data. When masking
      methods are used for disclosure limitation purposes, statistical methods must be
      adjusted for the locational uncertainty of geocoded data. We conclude that
      selection of one particular type of geographic area as the geocode may
      unnecessarily constrain future work. Therefore, the longitude and latitude of
      each case is the superior basic geocode; all other geocodes of interest can be
      constructed from this basic identifier.

PMID- 16458787
TI  - Basic mapping principles for visualizing cancer data using Geographic Information
      Systems (GIS).
AB  - Maps and other data graphics may play a role in generating ideas and hypotheses
      at the beginning of a project. They are useful as part of analyses for evaluating
      model results and then at the end of a project when researchers present their
      results and conclusions to varied audiences, such as their local research group,
      decision makers, or a concerned public. Cancer researchers are gaining skill with
      geographic information system (GIS) mapping as one of their many tools and are
      broadening the symbolization approaches they use for investigating and
      illustrating their data. A single map is one of many possible representations of
      the data, so making multiple maps is often part of a complete mapping effort.
      Symbol types, color choices, and data classing each affect the information
      revealed by a map and are best tailored to the specific characteristics of data.
      Related data can be examined in series with coordinated classing and can also be
      compared using multivariate symbols that build on the basic rules of symbol
      design. Informative legend wording and setting suitable map projections are also
      basic to skilled mapmaking.

PMID- 16458788
TI  - How (not) to lie with spatial statistics.

PMID- 16458789
TI  - Cancer map patterns: are they random or not?
AB  - BACKGROUND: Maps depicting the geographic variation in cancer incidence,
      mortality or treatment can be useful tools for developing cancer control and
      prevention programs, as well as for generating etiologic hypotheses. An important
      question with every cancer map is whether the geographic pattern seen is due to
      random fluctuations, as by pure chance there are always some areas with more
      cases than expected, or whether the map reflects true underlying geographic
      variation in screening, treatment practices, or etiologic risk factors. METHODS:
      Nine different tests for spatial randomness are evaluated in very practical
      settings by applying them to cancer maps for different types of data at different
      scales of spatial resolution: breast, prostate, and thyroid cancer incidence;
      breast cancer treatment and prostate cancer stage in Connecticut; and nasopharynx
      and prostate cancer mortality in the U.S. RESULTS: Tango's MEET, Oden's Ipop, and
      the spatial scan statistic performed well across all the data sets. Besag
      Newell's R, Cuzick-Edwards k-NN, and Turnbull's CEPP often perform well, but the
      results are highly dependent on the parameter chosen. Moran's I performs poorly
      for most data sets, whereas Swartz Entropy Test and Whittemore's Test perform
      well for some data sets but not for other. CONCLUSIONS: When publishing cancer
      maps we recommend evaluating the spatial patterns observed using Tango's MEET, a
      global clustering test, and the spatial scan statistic, a cluster detection test.

PMID- 16458790
TI  - Recent changes in the spatial pattern of prostate cancer in the U.S.
AB  - INTRODUCTION: Spatial-temporal trends in prostate cancer mortality are of
      interest because of the introduction and increasing use of the prostate-specific
      antigen (PSA) screening test after 1986. This article describes spatial-temporal
      changes in U.S. prostate cancer mortality from 1968 to 1998. METHODS: Prostate
      cancer mortality data were obtained from Compressed Mortality Files available
      from the National Center for Health Statistics. To minimize potential problems
      such as small numbers or missing data, the analysis was limited to white males
      aged 25 and over, and located in 2970 counties with complete data. Statistical
      analyses included the global distance between observed and expected multinomial
      probabilities, Hoover's Index of Concentration, and a retrospective test for
      change in spatial patterns. RESULTS: Fairly steady declines were observed in
      prostate cancer mortality from 1968 until 1993, with an increasing tendency
      toward spatial uniformity. Spatial concentration increased from 1994 to 1998, and
      by 1998 the level of spatial concentration had returned to levels that prevailed
      during the early to mid-1980s. Comparing 1991-1998 to 1968-1990, the observed
      number of prostate deaths increased the most rapidly with respect to the expected
      number in western Appalachia and the south central U.S. Recent relative declines
      in mortality were observed in southern California and parts of Florida.
      CONCLUSIONS: The observed results are generally consistent with prior evaluations
      of prostate cancer spatial-temporal patterns. However, the current study
      identified a heretofore unnoticed recent pattern of change in western Appalachia
      and the south central U.S. Recent declines in Florida and southern California may
      have contributed to recent increases in spatial concentration of prostate cancer
      mortality, and may possibly be associated with realized benefits from screening
      programs.

PMID- 16458791
TI  - Clusters of census tracts with high proportions of men with distant-stage
      prostate cancer incidence in New Jersey, 1995 to 1999.
AB  - BACKGROUND: Although the etiology of prostate cancer is uncertain, cancer control
      programs need to know the factors that contribute to variations in prostate
      cancer incidence from place to place. Geographic patterns of prostate cancer
      cases diagnosed at the distant stage are particularly important, because survival
      is substantially lower than for prostate cancer diagnosed at earlier stages. The
      purpose of this study was to identify and characterize clusters of census tracts
      in New Jersey with significantly high proportions of men diagnosed with distant
      stage prostate cancer. METHODS: Prostate cancer cases diagnosed in New Jersey
      residents from 1995 to 1999 (n=30,505) were geocoded at the census tract level
      (n=1938) based on their residences at time of diagnosis. A spatial scan statistic
      (SaTScan) then was applied to identify clusters of census tracts with elevated
      proportions of cases of distant stage prostate cancer, using a case-control
      Bernoulli probability model study design. Distant-stage prostate cancers were
      defined as cases (n=1230), and all other prostate cancers as controls. Population
      characteristics from the 1990 Census for the area of the most likely cluster were
      compared to the remainder of the state. RESULTS: SaTScan identified a large
      geographic area in northeast New Jersey as the most likely cluster (RR=1.25,
      p=0.001). Compared to the remainder of the state, the underlying population in
      the most likely cluster area had higher proportions of African-American,
      Hispanic, and Asian men, and was more likely to be foreign-born, undereducated,
      in poverty, and have limited English speaking ability. CONCLUSIONS: Spatial
      analyses of late stage prostate cancer cases can provide additional insights into
      less favorable outcomes for disadvantaged populations and racial and ethnic
      minorities.

PMID- 16458792
TI  - Spatial analysis of prostate cancer incidence and race in Virginia, 1990-1999.
AB  - BACKGROUND: Racial disparities exist in prostate cancer incidence. An important
      contributor to these disparities may be socioeconomic status. METHODS: Virginia
      Cancer Registry data, 1990-1999 (37,373 cases) were geocoded to the Census tract
      and county level. The annualized, age-adjusted incidence rates for African
      Americans and whites were calculated, and crude and smoothed maps of these rates
      were produced. Statistical tests for clustering of cases were conducted. Prostate
      cancer incidence was statistically modeled as a function of area-based measures
      of poverty, median household income, education, rural status, ratio of physicians
      to population in each county, percentage of men in each county obtaining prostate
      cancer screening with the prostate-specific antigen (PSA) test, and percent of
      households headed by females. RESULTS: Prostate cancer incidence was elevated in
      the eastern and central portions of the state. Statistical tests for clustering
      were highly significant (Tango's test, p<0.008; spatial scan statistic, p<0.001).
      Poverty and lower education were associated with a decreased incidence among
      whites but not African Americans. Median household income and urban status were
      positively associated with incidence for both populations. Among whites,
      increased percent of female heads of households and ratio of physicians per
      population were associated with increased incidence. Associations between
      predictor variables and prostate cancer incidence were seen only in the census
      tract level analyses. CONCLUSIONS: Overall, the findings support the argument
      that area measures of poverty and education do not explain the increased
      incidence of prostate cancer among African Americans. Other factors, such as
      dietary practices, may help explain racial disparities in prostate cancer
      incidence. Because of the large differences between tract and county level
      results, the time and expense of obtaining data geocoded to the tract level seems
      worthwhile.

PMID- 16458793
TI  - What can geography tell us about prostate cancer?
AB  - One of the most striking characteristics of prostate cancer is the degree of
      geographic variation in its patterns of occurrence and progression; this
      variation is apparent at local, national, and international levels. Although
      geographic theory, methods, and data are increasingly utilized for public health
      research, epidemiologic research in prostate cancer etiology and progression has
      not taken full advantage of the spatial sciences as partner disciplines. This
      article reviews the known factors influencing the biology and epidemiology of
      prostate cancer and some of the ways in which findings to date have benefited
      from geography. A model is presented for geographically integrated research in
      prostate cancer, with discussion of how spatially referenced data and methods
      could enhance approaches to answering remaining questions in prostate cancer.

PMID- 16458794
TI  - Missing stage and grade in Maryland prostate cancer surveillance data, 1992-1997.
AB  - BACKGROUND: Missing data in cancer surveillance records are common; however,
      little information exists on the types of cases most likely to have missing data,
      or how missing data influence research or policy. Two clinical elements often
      missing in surveillance data are histologic grade and stage of disease. Missing
      data are either not clinically ascertained or not successfully abstracted.
      METHODS: Prostate cancer cases (N=22,217) reported to the Maryland Cancer
      Registry during 1992-1997 were geocoded by residence and analyzed. Multi-level
      logistic regression was used to examine case attributes and area-level
      demographic, economic, and health services characteristics predictive of either
      missing stage or grade. A scanning statistic was used to explore geographic
      clustering of high and low rates of missing stage and grade within the state,
      before and after adjustment for significant variables from multi-level models.
      RESULTS: Older age, black race, missing grade, and higher county-level median
      income increased the likelihood of missing stage, whereas more recent year of
      diagnosis, higher blockgroup-level median income, and county-level rurality
      decreased the likelihood. Older age, missing or later stage, higher blockgroup
      level median income, and more urologists per case in one's county of residence
      increased the likelihood of missing tumor grade, and more recent year of
      diagnosis, higher county-level median income, and rurality decreased the
      likelihood. Adjustment reduced statistically significant clusters of missing
      stage from six to two, and clusters of missing grade from three to zero.
      CONCLUSIONS: Results suggest systematic influences on missing stage and grade,
      which could be investigated with case-control follow-back studies.

PMID- 16458795
TI  - Hierarchical modeling and other spatial analyses in prostate cancer incidence
      data.
AB  - BACKGROUND: State central cancer registries are often asked to respond to
      questions about the spatial distribution of cancer cases. Spatial analysis
      methods and technology are evolving rapidly, and can be a considerable challenge
      to registries that do not have staff with training in this area. The purpose of
      this article is to describe a general methodological approach that potentially
      might be a starting point for many cancer registry spatial analyses at the county
      level. METHODS: Prostate cancer incident cases (N=31,159) from the Louisiana
      Tumor Registry from 1988 to 1999 were used for illustrative purposes. To explore
      spatio-temporal patterns, analyses focused on four time periods, each 3 years in
      length: 1998-1990, 1991-1993, 1994-1996, and 1997-1999. For each time period,
      race-specific (white and black), direct age-adjusted incidence rates and indirect
      standardized incidence ratios (SIRs) were calculated, smoothed using Bayesian
      methods, and assessed for evidence of spatial autocorrelation using global and
      local Moran's I. Hierarchical generalized linear models (HGLM) were fitted to
      identify significant covariates. Clusters of elevated and lower rates were
      identified using a spatial scan statistic (SaTScan). RESULTS: Temporal trends in
      SIRs in both race groups were consistent with the introduction of prostate
      specific antigen (PSA) testing in Louisiana during the late 1980s and early
      1990s, but possibly with a lag in black males. Clusters of lower than expected
      values were observed for white males in the central (p=0.001) and southeastern
      coastal areas (p=0.001), and to a greater extent for black males in the central
      (p=0.001), southwestern and southeastern coastal parishes (p=0.001). CONCLUSIONS:
      Mapping disease occurrence by time period is an effective way to explore spatio
      temporal patterns. HGLM models and software are available to control for
      covariates and for unstructured and spatially structured variability that may
      confound spatial variability patterns.

PMID- 16458796
TI  - Long-term results of acromioclavicular joint coplaning.
AB  - PURPOSE: Coplaning removes medial acromial spurs and portions of the distal
      clavicle with an arthroscopic subacromial decompression (ASD). Concerns exist
      that this violates inferior acromioclavicular (AC) ligaments and increases AC
      joint mobility, resulting in long-term problems. The purpose of this study was to
      re-evaluate 3 cohorts of patients who underwent ASD with various degrees of
      coplaning and to determine if late AC joint tenderness or reoperation had
      occurred. TYPE OF STUDY: Nonrandomized control study. METHODS: Eighty-one
      patients undergoing ASD were divided into 3 groups. Group 1 (24) underwent
      removal of inferior clavicle osteophytes, group 2 (34) had a distal clavicle
      hemiresection with up to 50% of the articular cartilage removed, and group 3 (23)
      had complete distal clavicle resection. Radiographs, charts, and arthroscopic
      videotapes were reviewed to determine the amount of clavicle removed. Follow-up
      evaluations included Constant-Murley, American Shoulder and Elbow Surgeons
      (ASES), SANE, and Rowe shoulder scores with special attention given to AC joint
      pain and additional procedures. RESULTS: The average patient age was 46 years
      (range, 19 to 81 years) and follow-up was 73 months. At follow-up, the average
      Constant, ASES, Row, and SANE scores were: for group 1, 97.1, 97.5, 96.9, and
      95.8, respectively; for group 2, 95.1, 97.4, 96, and 92.8, respectively; and for
      group 3, 96.3, 98.3, 96.1, and 95.7. No patient required additional shoulder
      surgery. CONCLUSIONS: Coplaning did not increase AC joint symptoms, compromise
      clinical results, or lead to additional surgery at an average follow-up of 6
      years. LEVEL OF EVIDENCE: Level IV, therapeutic case series study.

PMID- 16458797
TI  - A biomechanical and radiographic analysis of standard and intracortical suture
      anchors for arthroscopic rotator cuff repair.
AB  - PURPOSE: To compare the fixation strength and radiographic motion of an anchor
      designed for intracortical (IC) fixation (FT Anchor, Arthrex, Naples, FL) with
      that of standard anchors used for rotator cuff repair. TYPE OF STUDY: In vitro
      human cadaveric biomechanical study. METHODS: Four types of metallic suture
      anchors (8 per group) were randomly inserted into human cadaveric humeri using an
      IC anchor and 3 types of standard anchors. Anchors were inserted 45 degrees to
      the humeral head surface and 90 degrees to the rotator cuff line of action.
      Anchors were tested under physiologic loads for 500 cycles followed by a failure
      test. The number of cycles, failure mode, and failure load were recorded.
      Fluoroscopy was used to measure rotation and displacement of the anchor within
      the humeral head during testing. Data were analyzed using a 1-way analysis of
      variance with a correction for multiple comparisons. RESULTS: There were no
      significant differences in anchor displacement or rotation measured by
      fluoroscopy after cyclic loading. Total construct displacement across anchors
      ranged from 4.9 to 7.8 mm, well beyond the 3-mm failure criterion reported in the
      literature. The IC anchor had a statistically significant greater failure load
      than the other devices. There was no significant difference in failure load
      between the other 3 anchors. The anchor had the greatest number of cycles to 3 mm
      of failure. This was not significantly different than the TwinFix anchor (Smith &
      Nephew, Andover, MA), but both values were significantly greater than both the
      Super Revo (Linvatec, Largo, FL) and Fastin RC (DePuy Mitek, Raynham, MA)
      anchors. CONCLUSIONS: Anchor motion accounted for about one third of total
      displacement of the suture/anchor construct. IC fixation anchors performed well
      compared with standard anchors in human cadaveric bone. CLINICAL RELEVANCE:
      Fluoroscopic imaging showed both rotation and displacement of the anchor within
      the humeral head which may contribute to early gap formation after rotator cuff
      repairs.

PMID- 16458798
TI  - Outcomes of isolated type II SLAP lesions treated with arthroscopic fixation
      using a bioabsorbable tack.
AB  - PURPOSE: The objective was to clinically evaluate the treatment of type II Slap
      lesions repaired surgically using a bioabsorbable device. TYPE OF STUDY:
      Retrospective clinical follow-up study. METHODS: Forty-one patients with isolated
      type II SLAP lesions who were treated with arthroscopic fixation were identified.
      Patients were excluded for rotator cuff tears, instability, or subacromial
      decompression. Patients completed the L'Insalata and the American Society of
      Shoulder and Elbow Surgeons (ASES) questionnaires, and underwent a thorough
      shoulder examination at a minimum of 2 years postoperatively. RESULTS: At a mean
      of 3.7 years follow-up, 33 of 41 patients returned for physical examination and 6
      others returned the L'Insalata questionnaire. The mean L'Insalata and ASES scores
      were 86.7 and 86.8, respectively; 27 patients reported their satisfaction as good
      to excellent but only 14 of the 29 athletes returned to their preinjury level of
      athletics. The average ASES scores were statistically different in patients who
      had their rotator cuff pierced versus those who did not (P< .05). In addition, 13
      of 16 patients who experienced night pain had a cuff piercing approach.
      CONCLUSIONS: Despite high outcome scores, overall patient satisfaction was only
      71%. In addition, up to 41% continued to experience some degree of night pain.
      Patients treated with a rotator cuff piercing had a significantly poorer outcome.
      Moreover, the patients who were athletes performed poorer on their outcomes
      evaluation than did their nonathletic counterparts. Whereas the outcome scores
      overall were high, this problem is still difficult to treat successfully. This
      may be because of the high demands of athletes. The data also suggest that
      placing portals through the rotator cuff may be associated with poorer surgical
      outcomes. LEVEL OF EVIDENCE: Level III.

PMID- 16458799
TI  - A prospective, randomized, clinical and radiographic study after arthroscopic
      Bankart reconstruction using 2 different types of absorbable tacks.
AB  - PURPOSE: The aim of the study was to compare the clinical and radiographic
      results after arthroscopic Bankart reconstruction using 2 different types of
      absorbable implant. TYPE OF STUDY: Randomized controlled trial. METHODS: A
      randomized series of 40 patients who had recurrent, unidirectional, post
      traumatic shoulder instability were included in the study. All patients underwent
      an arthroscopic Bankart reconstruction involving either polygluconate co-polymer
      (PGACP group, n = 20) or self-reinforced poly-L-lactic acid polymer (PLLA group,
      n = 20) tack implants. The patients underwent clinical and radiographic
      assessments preoperatively and at 2 years. Additional radiographic assessments
      were performed at 6 months. RESULTS: Preoperatively, the study groups were
      comparable in terms of demographics as well as clinical parameters. One patient
      in each group had a redislocation (5%) during the follow-up period of 2 years. No
      subluxations were registered. No statistically significant differences were found
      between the study groups in terms of strength in abduction, range of motion, and
      Rowe or Constant scores. There was a significant increase in degenerative changes
      during the follow-up period in both study groups (P = .004). However, no
      significant differences in degenerative changes were registered between the study
      groups either preoperatively or at the 2-year follow-up. There were no
      significant differences in the radiographic visibility of the drill holes used
      for the absorbable implants between the study groups at the 6-month assessment.
      However, at the 2-year assessment, the radiographic visibility of the drill holes
      was significantly greater (P = .004) in the patients in the PLLA group than those
      in the PGACP group. At the 2-year assessment, no correlation was found between
      the appearance of the drill holes and the degenerative findings (PGACP group, rho
      = 0.44; PLLA group, rho = 0.42). CONCLUSIONS: Two years after arthroscopic
      Bankart reconstruction using either PGA polymer or PLA polymer implants, the
      overall clinical results were comparable. Radiographic assessments revealed that
      the degenerative changes increased in both study groups during the follow-up
      period. Furthermore, the visibility of the drill holes on the 2-year radiographs
      was greater after using PLLA implants than after using PGACP implants. LEVEL OF
      EVIDENCE: Level I.

PMID- 16458800
TI  - Functional changes in articular cartilage after meniscal allograft
      transplantation: a quantitative histochemical evaluation in rabbits.
AB  - PURPOSE: To evaluate quantitatively functional changes in articular cartilage
      after immediate and delayed meniscus transplantation in rabbits. TYPE OF STUDY:
      Experimental study. METHODS: Thirty rabbits were divided into 5 groups: groups A
      and C were subjected to meniscectomy only, groups B and D underwent meniscal
      transplantation immediately after meniscectomy, and group E had delayed
      transplantation 6 weeks after meniscectomy. Six nonoperated knees served as
      controls. Functional changes in articular cartilage were examined at 6 weeks
      (groups A, B) and 1 year (groups C, D, E, controls) after surgery by measuring
      proteoglycan content of the extracellular matrix as a measure of its quality and
      lactate dehydrogenase (LDH) activity in chondrocytes as a measure of their
      vitality. RESULTS: At 6-week and 1-year follow-up, no significant differences
      were found between the immediate transplant group and postmeniscectomy group. The
      delayed transplant group showed a significantly decreased proteoglycan content
      compared with the postmeniscectomy group. No significant differences in cellular
      LDH activity were found between the immediate transplant group and
      postmeniscectomy group at 6 weeks and 1 year. However, the delayed transplant
      group showed a significant decrease in LDH activity compared with the
      postmeniscectomy group. CONCLUSIONS: Immediate meniscal transplantation in
      rabbits did not significantly reduce degenerative changes of articular cartilage
      in comparison with meniscectomy on a short-term and long-term basis, whereas
      delayed transplantation led to more degenerative changes than meniscectomy.
      CLINICAL RELEVANCE: Before meniscus transplantation can be considered as an
      alternative to meniscectomy in clinical practice, it has to be determined whether
      this procedure has any protective effect on articular cartilage on the long term.

PMID- 16458801
TI  - Anatomic reconstructive surgery for posterolateral instability of the knee.
AB  - PURPOSE: We describe an anatomic reconstructive surgical procedure that
      simultaneously reconstructs the fibular collateral ligament, popliteal tendon,
      and popliteofibular ligament using split Achilles allograft, and compare the
      clinical results of this technique with those of the posterolateral corner sling
      procedure for posterolateral instability of the knee. TYPE OF STUDY: Case series.
      METHODS: Forty-six patients were treated for posterolateral instability of the
      knee between 1998 and 2002. The posterolateral corner sling procedure was
      performed in 25 patients (group A) and anatomic reconstructive surgery in 21
      patients (group B). The minimum follow-up was 12 months. In all cases,
      arthroscopic evaluation was performed. Clinical review included the Lysholm knee
      scores and varus laxity and tibial external rotation assessment. RESULTS: The
      mean Lysholm knee scores were 54.8 points in group A and 54.4 points in group B
      before surgery, and 86.9 and 93.6 points at the time of the latest follow-up,
      respectively (P < .05). Tibial external rotation of 5 degrees more than the
      contralateral uninjured knee was present in 12% of group A and in 5% of group B
      (P < .05). Varus laxity of 5 mm greater than the contralateral knee was observed
      in 28% of group A and in 14% of group B (P < .05). CONCLUSIONS: Anatomic
      reconstruction of the posterolateral corner resulted in less varus laxity and
      tibial external rotation than did the posterolateral corner sling procedure.
      LEVEL OF EVIDENCE: Type IV, case series, no or historical control group.

PMID- 16458802
TI  - Thermal medial retinaculum shrinkage and lateral release for the treatment of
      recurrent patellar instability.
AB  - PURPOSE: To study a technique of medial retinacular thermal shrinkage and
      evaluate the clinical effectiveness of this technique. TYPE OF STUDY:
      Nonrandomized prospective case series. METHODS: A consecutive series of patients
      with recurrent patellar instability treated with arthroscopic lateral release and
      medial thermal retinaculum shrinkage using a monopolar radiofrequency probe was
      assessed subjectively by visual analog scale and both preoperatively and
      postoperatively by physical examination and Lysholm and Fulkerson knee scores.
      RESULTS: We evaluated 53 knees with an average follow-up of 53 months (range, 24
      to 88 months). The mean Lysholm and Fulkerson scores improved from 45 and 41 to
      81 and 82, respectively. Subjectively, 48 of 53 knees (90%) were reported as
      excellent or good. The average visual analog scale score was 8 out of 10. Five
      patients failed because of recurrent dislocation (9% recurrence). Additional
      stabilization procedures were performed in 4 patients. CONCLUSIONS: Medial
      shrinkage using monopolar thermal energy is effective in treating recurrent
      patellar instability. Our results were comparable with prior studies using suture
      plication. The technique avoids additional incisions and decreases operative
      time. LEVEL OF EVIDENCE: Level IV, therapeutic prospective cohort study.

PMID- 16458803
TI  - Arthroscopic treatment of acute tibial avulsion fracture of the posterior
      cruciate ligament with suture fixation technique through Y-shaped bone tunnels.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of
      arthroscopic treatment of tibial avulsion fracture of the posterior cruciate
      ligament (PCL) with suture fixation technique through Y-shaped bone tunnels. TYPE
      OF STUDY: Retrospective case series. METHODS: We treated 29 cases of acute PCL
      tibial avulsion fracture arthroscopically through double posteromedial portals.
      The PCL and avulsion bony fragment was fixed with 2 No. 6 polyester sutures,
      which were pulled out through Y-shaped bone tunnels and fixed on a titanium
      button. The 2 branch openings of the Y-shaped bone tunnels were at the posterior
      edge of the tibial bed; the common outer opening was at medial side of the tibial
      tubercle. Through twisting of the button, the suture were tightened to ensure the
      fixation. The patients were followed-up for more than 2 years and were evaluated
      according to the International Knee Documentation Committee, Lysholm, and Tegner
      rating scales. RESULTS: There was no extension limitation. Except for 2 patients
      who had 5 degrees flexion limitation, all the patients gained normal flexion.
      Before surgery, all patients had 1 degrees to 2 degrees positive posterior drawer
      test, and KT-1000 examination showed that the side-to-side difference of the
      posterior drawer test was 7 to 14 mm, with an average of 10.3 +/- 1.7 mm. At the
      last follow-up, 1 patient had 1 degrees positive posterior drawer test, the other
      patients had negative posterior drawer tests. The side-to-side difference of the
      posterior drawer test was 0 to 2 mm in 28 patients, and 4 mm in 1 patient, with
      an average of 0.6 +/- 0.4 mm. The Lysholm score was 93 to 100, with an average of
      97.4 +/- 1.4. The Tegner scores were 6.8 +/- 0.8 before injury, and 6.6 +/- 0.7
      at the last follow-up (P > .05). CONCLUSIONS: Arthroscopic treatment of acute
      tibial avulsion fracture of the PCL with this fixation technique can restore the
      stability and function of the joint in most patients. Visualization and
      manipulation through double posteromedial portals are convenient. Y-shaped bone
      tunnels and the button-twisting technique are useful to ensure the results of
      reduction and fixation. LEVEL OF EVIDENCE: Level IV.

PMID- 16458805
TI  - Tunnel convergence in combined anterior cruciate ligament and posterolateral
      corner reconstruction.
AB  - PURPOSE: To examine the geometric relationship between tunnels created in the
      lateral femoral condyle in reconstruction of the anterior cruciate ligament (ACL)
      and the posterolateral structures. METHODS: The geometric relationship between a
      standard ACL tunnel and 11 lateral femoral tunnel variations in synthetic femur
      specimens was examined. Tunnel collision frequency and tunnel separation were
      measured radiographically. Subsequent evaluation was performed on 7 paired
      cadaveric specimens (14 knees) to access the efficacy of 2 configurations.
      RESULTS: Phase I-Tunnel collision frequency was 0% and 58% for 25-mm and 30-mm
      tunnel depths, respectively. Axial angles greater than 40 degrees and coronal
      angles > or =20 degrees resulted in unsafe configurations. The safest position
      for lateral tunnel placement was straight lateral approach (0 degrees in the
      coronal plane) with increased axial plane orientation (hand dropped toward the
      floor 40 degrees). The safe zone for lateral tunnel configuration was determined
      to be between [0,0] and [0,40] ([coronal, axial]). Phase II--Control group
      ([0,0]) collision frequencies were 43% and 86% for the 25-mm 30-mm tunnels,
      respectively. Experimental group ([0,40]) collision frequencies were 29% and 43%
      for the 25-mm and 30-mm tunnel, respectively. In femoral condyles measuring <35
      mm, collision rates were 100% versus 0% in the control group ([0,0]) versus the
      experimental group ([0,40]). In specimens where no collision was seen, tunnel
      separation distance was 4.5 +/- 4.4 mm and 5.8 +/- 2.2 mm for the control and
      experimental groups, respectively (P = .39). CONCLUSIONS: Tunnel collision
      occurred often. Tunnel collision is dependent on femoral condyle geometry, tunnel
      depth, and tunnel configuration. To minimize the potential for tunnel collision,
      the surgeon should maintain a neutral alignment in the coronal plane, limit
      lateral tunnel depth to < or =25 mm, and direct the lateral tunnel anteriorly in
      the axial plane to a maximum of 40 degrees. CLINICAL RELEVANCE: This study
      describes guidelines for tunnel placement to prevent tunnel collision when
      performing combined ACL and posterolateral corner reconstruction.

PMID- 16458804
TI  - Combined anterior cruciate ligament, posterior cruciate ligament, and
      posterolateral corner reconstruction with autogenous hamstring grafts in chronic
      instabilities.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical outcome after 1
      stage reconstructions of the anterior and posterior cruciate ligaments (ACL, PCL)
      with reconstruction of the posterolateral corner (PLC) structures using
      autogenous hamstring grafts in chronic knee injuries. TYPE OF STUDY: Prospective
      case series. METHODS: We reviewed 17 patients (13 men and 4 women) with chronic
      multiligamentous injuries after a minimum follow-up of 2 years (range, 24 to 66.3
      months). Arthroscopically assisted combined ACL/PCL reconstructions with
      autogenous semitendinosus-gracilis tendon grafts were performed using the single
      incision endoscopic ACL technique and the single femoral tunnel, single-bundle
      transtibial tunnel PCL technique. The PLC was reconstructed with a free
      autogenous semitendinous tendon graft. The primary outcome measures were the
      International Knee Documentation Committee (IKDC) score and stress radiography.
      As secondary outcome measure, all patients were evaluated with a subjective
      questionnaire, physical examination, radiologic assessment, and KT-1000
      arthrometer testing. RESULTS: The mean time from injury to the reconstructive
      procedure was 70.2 +/- 96.7 months (range, 5.1 to 312.6 months). At final IKDC
      evaluation, 4 patients (29.4%) were graded level B (nearly normal), 10 patients
      (58.8%) level C (abnormal), and 2 patients (11.8%) level D (grossly abnormal).
      The mean postoperative subjective IKDC score was 71.8 +/- 19.3 points. Mean
      posterior tibial displacement as measured through stress radiography at 90
      degrees of knee flexion was reduced from -15.06 +/- 4.68 mm preoperatively to 
      7.12 +/- 3.37 mm postoperatively (P < .001). Mean anterior tibial displacement
      was 0.94 +/- 2.75 mm preoperatively compared with -1.59 +/- 3.50 mm
      postoperatively (P < .01). Three patients had a fixed posterior tibial
      subluxation (posterior tibial displacement < or = -3 mm on anterior stress
      radiographs) postoperatively. Severe subjective instability was reduced
      significantly by the operative procedure (P < .001). The mean postoperative total
      anterior-posterior side-to-side difference with the KT-1000 arthrometer testing
      was 2.00 +/- 2.23 mm (range, -4 to 7 mm). CONCLUSIONS: Combined chronic
      ACL/PCL/PLC instabilities can be successfully treated with 1-stage arthroscopic
      cruciate ligament reconstruction combined with PLC reconstruction using
      autogenous hamstring grafts. Although current reconstruction techniques are not
      able to restore normal tibiofemoral kinematics, most patients recover a
      functionally stable knee and have considerably improved knee function compared
      with their preoperative status, based on subjective parameters and objective
      criteria. LEVEL OF EVIDENCE: Level IV, case series, no historical or control
      group.

PMID- 16458806
TI  - Magnetic resonance imaging evaluation of biodegradable transfemoral fixation used
      in anterior cruciate ligament reconstruction.
AB  - PURPOSE: The study was designed to evaluate bioabsorbable transfemoral fixation
      in anterior cruciate ligament (ACL) reconstruction using hamstring tendon as
      graft. Magnetic resonance imaging (MRI) was used to assess the continuity of the
      bioabsorbable implant at different stages of the patients' rehabilitation. TYPE
      OF STUDY: Retrospective case series. METHODS: Forty-nine patients underwent ACL
      reconstruction performed by a single surgeon. The graft, a tensioned quadrupled
      semitendinosus tendon, was fixed proximally using a bioabsorbable TransFix
      implant (Arthrex, Naples, FL). The patients underwent an accelerated
      rehabilitation program and were assessed clinically at regular intervals
      postoperatively using MRI, with specific attention focused on the implant.
      RESULTS: The average time from surgery to MRI was 28 weeks (range, 4 to 54
      weeks). All implants were fully visible with no evidence of resorption. Five
      implants were fractured at an average of 20 weeks postoperatively (range, 9 to 47
      weeks). Three implants showed deformation but no definite fracture at an average
      of 14 weeks (range, 12 to 17 weeks). This amounts to 16% of implants with
      fractures or deformation, many close to the period of theoretical graft
      incorporation. All patients were clinically stable with no symptoms or signs or
      instability on clinical review and all had returned to preinjury sporting
      activities. CONCLUSIONS: Transfemoral biodegradable implants have the potential
      to fracture or deform during their postoperative course in tensioned hamstring
      tendon ACL reconstruction. Although no apparent detrimental effect was found in
      our series, further research is needed on this device before it can be
      recommended for ACL reconstruction. We also question the idea that rigid fixation
      for the ACL graft for the entire healing process is required. LEVEL OF EVIDENCE:
      Level IV, retrospective case series.

PMID- 16458807
TI  - Revision anterior cruciate ligament reconstruction with quadriceps tendon
      patellar bone autograft.
AB  - PURPOSE: To evaluate the cause of recurrent pathologic instability after anterior
      cruciate ligament (ACL) surgery and the effectiveness of revision reconstruction
      using a quadriceps tendon autograft using a 2-incision technique. TYPE OF STUDY:
      Retrospective follow-up study. METHODS: Between 1999 and 2001, 31 patients
      underwent ACL revision reconstruction because of recurrent pathologic instability
      during sports or daily activities. Twenty-eight patients were reviewed after a
      mean follow-up of 4.2 years (range, 3.3 to 5.6 years). The mean age at revision
      surgery was 27 years (range, 18 to 41 years). The average time from primary
      procedure to revision surgery was 26 months (range, 9 to 45 months). A clinical,
      functional, and radiographic evaluation was performed. Also magnetic resonance
      imaging (MRI) or computed tomography (CT) scanning was performed. The
      International Knee Documentation Committee (IKDC), Lysholm, and Tegner scales
      were used. A KT-1000 arthrometer measurement (MEDmetric, San Diego, CA) by an
      experienced physician was made. RESULTS: Of the failures, 79% had radiographic
      evidence of malposition of their tunnels. In only 6 cases (21%) was the
      radiologic anatomy of tunnel placement judged to be correct on both the femoral
      and tibial side. The MRI or CT showed, in 6 cases, a too-centrally placed femoral
      tunnel. After revision surgery, the position of tunnels was corrected. A
      significant improvement of Lachman and pivot-shift phenomenon was observed. In
      particular, 17 patients had a negative Lachman test, and 11 patients had a grade
      I Lachman with a firm end point. Preoperatively, the pivot-shift test was
      positive in all cases, and at last follow-up in 7 patients (25%) a grade 1+ was
      found. Postoperatively, KT-1000 testing showed a mean manual maximum translation
      of 8.6 mm (SD, 2.34) for the affected knee; 97% of patients had a maximum manual
      side-to-side translation <5 mm. At the final postoperative evaluation, 26
      patients (93%) graded their knees as normal or nearly normal according to the
      IKDC score. The mean Lysholm score was 93.6 (SD, 8.77) and the mean Tegner
      activity score was 6.1 (SD, 1.37). No patient required further revision. Five
      patients (18%) complained of hypersensitive scars from the reconstructive surgery
      that made kneeling difficult. CONCLUSIONS: There were satisfactory results after
      ACL revision surgery using quadriceps tendon and a 2-incision technique at a
      minimum 3 years' follow-up; 93% of patients returned to sports activities. LEVEL
      OF EVIDENCE: Level IV, case series, no control group.

PMID- 16458808
TI  - Role of hip arthroscopy in the diagnosis and treatment of hip joint pathology.
AB  - PURPOSE: Hip arthroscopy is growing in importance and relevance in the detection
      and treatment of various pathologies affecting the hip joint. There are a number
      of indications, including diagnosis and treatment of labral tears, extraction of
      loose bodies, and synovial-based diseases. Reports in the literature cite few
      complications arising from this minimally invasive procedure in a joint that has
      been difficult to access. The purpose of our study was to assess the efficacy and
      role of hip arthroscopy in the management of hip joint pathology. TYPE OF STUDY:
      Retrospective review of a consecutive series of 22 patients over a 44-month
      period. METHODS: The indications for surgery included ongoing hip pain for more
      than 6 months. Sixteen patients underwent contrast-enhanced magnetic resonance
      imaging scans, including all patients with mechanical symptoms. The procedure was
      performed as day surgery and all the patients were available for follow-up. They
      were assessed for pain, mechanical symptoms, activity levels, and sporting
      activities. RESULTS: All patients were assessed by means of a questionnaire and
      allocated scores out of a maximum of 100 points. The most significant improvement
      was seen in the group of patients (n = 10) who had mechanical symptoms with
      definite labral pathology confirmed and treated arthroscopically. Their scores
      improved from an average of 64 preoperatively to 90 postoperatively. There were
      no complications in our series. CONCLUSIONS: Hip arthroscopy represents an
      effective tool in treating hip joint pathology with reasonable expectations of
      success and a minimal complication rate. LEVEL OF EVIDENCE: Level IV.

PMID- 16458809
TI  - Electronic medical records for the arthroscopic surgeon.
AB  - Electronic medical records (EMR) are being used increasingly in health care. Many
      of these have been developed for large hospitals and primary care physicians. As
      physicians recognize the potential benefits of increased office efficiency and
      improved patient care, smaller practices and specialist are beginning to evaluate
      EMRs. The purpose of this review is to discuss the various aspects of an EMR for
      the arthroscopic surgeon. Surgeons should carefully understand their specific
      needs and how various EMRs can meet those needs.

PMID- 16458810
TI  - Arthroscopic excision of the talar Stieda's process.
AB  - One of the causes of posterior ankle pain is posterior impingement syndrome. When
      the talar lateral process is long, in which case it is called Stieda's process,
      it may be impinged between the tibia and calcaneus. We report the case of a 19
      year-old patient who complained of posterior ankle pain and was diagnosed with
      posterior impingement of Stieda's process. He failed to respond to conservative
      treatment and thus underwent arthroscopic excision. The ankle was approached
      through standard posterior lateral and trans-Achilles portals. A 4.5-mm diameter
      30 degrees arthroscope was used. Soft tissues around the talus were cleared with
      the help of a motorized shaver; after this, the posterior aspect of the subtalar
      joint could be visualized. The Stieda's process was seen to impinge between the
      tibia and the calcaneus in forced plantar flexion. The talar process was removed
      with a burr until the impingement disappeared. The patient returned to contact
      sports 8 weeks after surgery. Arthroscopic excision of the lateral process of the
      talus can be accomplished easily and return to sports is achieved in a relatively
      short time.

PMID- 16458811
TI  - Intra-articular protrusion of malpositioned Transfix implant following anterior
      cruciate ligament reconstruction.
AB  - We report on a case of stiffness of the knee following reconstruction of the
      anterior cruciate ligament caused by a Transfix implant (Manufacturer, City,
      State) protruding into the medial retinacular area. After a skiing injury, a 56
      year-old woman had a complete rupture of the anterior cruciate ligament along
      with a tear of the medial collateral ligament. She had an immediate anterior
      cruciate ligament reconstruction. A hinged brace was put on postoperatively. She
      presented to this institution 2 months after surgery with pain, stiffness, and
      decreased range of motion. Magnetic resonance imaging showed protrusion of the
      bioabsorbable implant in the medial retinacular area. Scar tissue was seen around
      the tip of the implant, medial retinacular area, and in the medial gutter. The
      terminal end of the protruding screw and the excess of scar tissue were removed
      arthroscopically. At the end of surgery, her on-table range of motion of the knee
      was 0 degrees to 120 degrees. She recovered well after physiotherapy and at the 3
      month follow-up she was pain free and had virtually full flexion. The knee seemed
      stable and the medial collateral ligament showed signs of healing. Caution has to
      be exercised in the choice of size and angle of insertion of the Transfix
      implant.

PMID- 16458812
TI  - Arthroscopic fixation of the subscapularis tendon in the reverse Hill-Sachs
      lesion for traumatic unidirectional posterior dislocation of the shoulder.
AB  - Posterior unidirectional instability of the shoulder following trauma is
      frequently associated with a cartilage-bone defect on the anterior joint surface
      of the humeral head. This defect can catch on the posterior joint surface during
      internal rotation of the arm, which causes redislocation of the humeral head in a
      posterior direction, thus increasing joint destruction. We describe a new
      arthroscopic surgical technique in which the subscapularis tendon is mobilized
      and attached to the defect using nonabsorbable or bioabsorbable suture anchors.
      In an manner analogous to open surgery with arthrotomy and transposition of the
      subscapularis tendon insertion into the defect, this arthroscopic technique fills
      up the defect, blocks extension during internal rotation of the arm, and safely
      avoids redislocation of the humeral head in a dorsal direction. The arthroscopic
      technique we describe is easy and safe to perform. Complicated tightening of the
      posterior joint capsule is no longer necessary following acute injury.

PMID- 16458813
TI  - Arthroscopically assisted acromioclavicular joint reconstruction.
AB  - Arthroscopically assisted acromioclavicular joint reconstruction avoids the large
      incisions necessary with open reconstructions. This acromioclavicular joint
      reconstruction technique via the subacromial space does not violate the rotator
      interval or require screw removal. The patient is placed in a modified beach
      chair position. The arthroscope is placed into the subacromial space, and a
      bursectomy is performed through a lateral subacromial portal. The coracoacromial
      ligament is released from the acromion with an electrocautery and an arthroscopic
      elevator. A nonabsorbable suture is passed through the coracoacromial ligament
      with a suture passer, and an arthroscopic suture grasper is used to deliver both
      ends of the suture out through the lateral portal. The coracoid is identified and
      isolated using a radiofrequency ablator placed through the anterior portal while
      visualizing through the lateral portal. A percutaneous shuttle device is passed
      through the skin superomedial to the coracoid. The shuttle is visualized entering
      superior to the coracoid and is passed just medial to the coracoid. Once the tip
      of the shuttle can be visualized in the recess inferior to the coracoid, the
      shuttle loop is advanced. A suture grasper is used to deliver both ends of the
      shuttle out through the anterior portal. A semitendinosus allograft is used to
      reconstruct the coracoclavicular ligament. A nonabsorbable suture is passed
      through both ends of the allograft. Three strands of nonabsorbable suture are
      braided together. The tendon and the braided suture are shuttled around the
      coracoid. At this point, both the braided suture and the allograft tendon enter
      the anterior portal, wrap around the coracoid base, and exit the anterior portal.
      A 3-cm incision is made over the distal clavicle. A hole is drilled through the
      clavicle with a 5-mm drill. A loop of 22-gauge wire is passed through the hole in
      the clavicle, and a looped suture is shuttled through the hole. A curved clamp is
      used to create a tunnel from the acromioclavicular joint, under the deltoid, to
      the anterior portal. The ends of the braided suture and the tendon sutures are
      grasped by the clamp and pulled out the acromioclavicular joint incision. The
      limbs of the braided suture and the tendon suture that pass medial to the
      coracoid are shuttled through the hole in the clavicle using the looped suture
      that was previously passed through the clavicle. The acromioclavicular joint is
      reduced by pushing down on the distal clavicle with a bone tamp while
      simultaneously lifting the acromion upward by superiorly loading the humerus at
      the elbow. Once the acromioclavicular joint is reduced or slightly over-reduced,
      the braided suture is tied down securely. The acromioclavicular joint should
      remain reduced even after the manual reduction maneuver is released. The
      semitendinosus allograft is tensioned around the distal end of the clavicle and
      sutured to itself with a nonabsorbable suture. The released coracoacromial
      ligament is retrieved from the clavicular incision and sutured to the distal
      clavicle and semitendinosus allograft. The incision is closed in standard
      fashion, and a sling is applied.

PMID- 16458814
TI  - Simple arthroscopic technique for rotator interval closure.
AB  - The rotator interval is a recognized source of pathology; there are several
      different techniques described for its closure but all require special
      instruments and skills. We present a technique that is simple in terms of skills
      and instrumentation. Two spinal needles are used. One needle is used as a suture
      retriever and the other as a suture passer. Each needle is passed through the
      margins of the rotator interval and, under arthroscopic vision, the needles are
      approximated to pass and retrieve the suture. Several sutures can be used as
      required. The knots are finally tied in an outside-inside fashion. This technique
      allows the surgeon to efficiently close the rotator interval under direct
      arthroscopic visualization in a few steps. The technique of arthroscopic rotator
      interval closure is simple, inexpensive, and easily reproducible.

PMID- 16458815
TI  - Footprint fixation for arthroscopic reconstruction in anterior shoulder
      instability: the Cassiopeia double-row technique.
AB  - Footprint fixation with a double-row technique is a new concept for arthroscopic
      capsulolabral reconstruction in anterior shoulder instability. The described
      double-row fixation technique with 2 suture anchors on the glenoid neck and 3 on
      the glenoid rim allows healing of the capsulolabral complex to a broader bony
      surface and not only to the thin glenoid rim as achieved with current techniques.
      Because the anchor insertion W-shaped form resembles the star constellation of
      Cassiopeia, this technique is called the Cassiopeia double-row technique. The
      restoration of the original capsulolabral footprint with the Cassiopeia double
      row technique by a stronger fixation should decrease recurrence rates of
      instability after arthroscopic stabilization but we need longer follow-up and
      larger numbers of patients to confirm.

PMID- 16458816
TI  - The posterior-medial portal.
AB  - Repair of the posterior superior labrum usually involves placing an anchor
      posterior to the biceps attachment through an anterior-superior or Wilmington
      portal. Access to the posterior-superior labrum can be accomplished by
      establishing a portal medial to the posterior viewing portal. The initial
      posterior arthroscopic viewing portal is established slightly lateral to a
      traditional position to allow viewing of the posterior labrum and maintain
      separation from the posterior-medial portal. The suture anchor can be placed
      behind the biceps attachment through an anterior portal. The posterior-medial
      portal is started approximately 3 cm medial to the viewing portal with an 18
      gauge needle. The needle is directed anterolateral into the intra-articular space
      under arthroscopic visualization to determine the appropriate course of the
      suture retriever. The needle is replaced with a sharp suture retrieval device.
      The suture from the anchor is pulled through the labrum to achieve a simple or
      mattress type repair. The suture is retrieved through the anterior-superior
      portal by finding it medial to the labrum. The sutures can be tied through the
      anterior-superior portal. The posterior-medial portal can be safely established
      with attention to technical considerations.

PMID- 16458817
TI  - Arthroscopic treatment of fractures of the radial head.
AB  - An original technique for the arthroscopic diagnosis and treatment of the
      fractures of the radial head is proposed and described. The elbow arthroscopy is
      started with a 4.5-mm 30 degrees arthroscope from the proximal anteromedial
      portal and the anterior elbow is examined; then a proximal anterolateral portal
      is created and a full-radius blade inserted to take out the hematoma and to allow
      visualization of the radial head that is explored through the whole range of
      motion to visualize the fracture fragment. The fragment is manipulated by means
      of arthroscopic tools to reduce the anteromedial surface of the radial head. The
      arthroscope is now switched to the posterolateral portal and the posterior aspect
      of the humeral radial joint is visualized. The soft spot portal is used to insert
      a periosteal elevator to complete the reduction and firmly hold the fragment in
      the reduced position. An anterolateral portal is now created to allow the safe
      insertion of a guidewire, angled 45 degrees to the longitudinal axis of the
      radius, to pierce the fragment with. A 14-mm long cannulated screw is inserted
      along the guide after specific drilling. Finally, the reduction and the stability
      of the fixation are checked with during full rotation of the elbow. The described
      procedure has been performed in 6 patients. Short-term preliminary results show a
      satisfactory functional outcome. Among the advantages of the technique are the
      minimally invasive approach, the direct visualization of the fracture, and the
      benefits derived from the radiation-free procedure.

PMID- 16458818
TI  - Failure of cerebrospinal fluid shunts: part I: Obstruction and mechanical
      failure.
AB  - Ventricular shunts are commonly employed to treat children with hydrocephalus.
      Complications from shunts are common and can present with a variety of signs and
      symptoms. This pair of reviews discusses the common findings in patients with
      shunt malfunction, including physical examination and imaging findings. Part I of
      the series discusses obstruction and mechanical failure of shunts; Part II
      discusses overdrainage, loculation, and abdominal complications of shunts. An
      understanding of the presentation and etiology of shunt dysfunction is critical
      for neurologists and pediatricians who often are the first to evaluate and triage
      these children.

PMID- 16458819
TI  - Acute infantile encephalopathy predominantly affecting the frontal lobes.
AB  - To establish a novel subtype of acute infantile encephalopathy, the clinical and
      radiologic features of nine infants with acute encephalopathy involving the
      bilateral frontal lobes were examined. These patients had convulsive status
      epilepticus with hyperpyrexia followed by a prolonged impairment of consciousness
      for 2-20 days. After the recovery of consciousness, all the patients manifested
      regression of verbal function and lack of spontaneity. Some of them also
      exhibited stereotypic movements, instability of mood, or catalepsy. Transient
      postictal edema in both frontal lobes was suggested by diffusion-weighted
      magnetic resonance imaging. Attenuated cerebral perfusion in the frontal lobes
      was demonstrated by single-photon emission computed tomography at the tenth day
      after onset or subsequently. Serial studies disclosed atrophic changes in the
      frontal lobes. All patients manifested regression or retardation of motor and
      verbal functions. The recovery of intellectual deficit was slower and less
      prominent than that of motor dysfunction. These unique features suggest that the
      frontal lobes are the focus of this novel subtype of acute encephalopathy, which
      we propose to call acute infantile encephalopathy predominantly affecting the
      frontal lobes.

PMID- 16458820
TI  - Responses to lumbar magnetic stimulation in newborns with spina bifida.
AB  - Searching for a tool to quantify motor impairment in spina bifida, transcranial
      and lumbar magnetic stimulation were applied in affected newborn infants. Lumbar
      magnetic stimulation resulted in motor evoked potentials in both the quadriceps
      muscle and the tibialis anterior muscle in most (11/13) subjects. However,
      transcranial magnetic stimulation did not lead to any response at all. A strong
      left-to-right correlation existed for amplitude and for latency. Lumbar magnetic
      stimulation proved to be applicable in newborn infants with spina bifida.
      Although current concepts regarding spina bifida suppose lower motor neuron
      dysfunction, the results of this study suggest that lower motor neuron integrity
      is at least partly preserved after birth. Transcranial magnetic stimulation does
      not lead to responses in healthy newborn infants because of insufficient
      synaptogenesis, myelinogenesis, and axon thickness. Therefore, conclusions on
      upper motor neuron function in spina bifida cannot be drawn. To what extent the
      method used here can achieve the aim of quantifying motor impairment is a matter
      of further study.

PMID- 16458821
TI  - Botulinum toxin type A for the treatment of the spastic equinus foot in cerebral
      palsy.
AB  - Muscle overactivity, one of the cardinal features of spasticity, is a common
      sequel of cerebral palsy. In this group of patients spasticity is responsible for
      several limitations that interfere with gait, causing variable functional
      disability. Drugs such as baclofen, tizanidine, or benzodiazepines, or even
      definitive treatments such as orthopedics or neurosurgeries are generally
      prescribed with uncertain results. The use of botulinum toxin type A has been
      frequently suggested for the treatment of spastic equinus foot in cerebral palsy,
      but few studies with adequate methodology support this idea. The present paper
      reviews and summarizes the data of published double-blind, randomized clinical
      trials to assess, with a meta-analysis, if botulinum toxin type A is an adequate
      treatment for spasticity caused by cerebral palsy. The results reveal a
      statistical superiority of botulinum toxin type A over placebo on gait
      improvement, tested using the Physician Rating Scale and Video Gait Analysis
      (Peto odds ratio = 3.99, 95% confidence interval = 2.20-7.22) in patients with
      spastic equinus foot. The botulinum toxin group also presented better results in
      the subjective assessment than the placebo group (Peto odds ratio = 3.49, 95%
      confidence interval = 1.50-8.12). Adverse events were more frequently observed
      after the use of botulinum toxin type A, but they were considered mild and self
      limited.

PMID- 16458822
TI  - Prevalence and characteristics of recurrent headaches in Turkish adolescents.
AB  - The objectives of this study were to determine the prevalence and characteristics
      of recurrent headaches and to investigate the sociodemographic differences
      between high school students with or without recurrent headaches from Izmir,
      Turkey. Multistep, stratified, cluster sampling method was used in this analytic,
      school-based cross-sectional study. Twenty-one schools were selected randomly,
      and 2384 preparatory, first-, second-, and third-grade high school students from
      84 different classrooms constituted the study cohort. The prevalence of recurrent
      headaches was 45.7% (1090/2384). Female students had a significantly higher
      headache frequency than males (P = 0.000). No significant relationship was
      evident between age and headache (P = 0.065). Also, there were no significant
      differences between the adolescents with or without headache for variables such
      as parental divorce (P = 0.052), existence of a step parent (P = 0.32), people
      with whom the students live at home (P = 0.186), number of siblings (P = 0.37),
      and maternal and paternal educational levels (P = 0.62 and P = 0.15,
      respectively). Headache frequency was higher when the income level of the
      student's family was lower (P = 0.016). Among the students who had headaches,
      53.3% had a medication, 37.3% were referred to a physician, and in 27.2% of them
      a diagnosis was established. School absenteeism with a ratio of 26.5% was a
      common problem among the students with headaches. These results indicate that
      approximately one half of Turkish high school students have recurrent headaches
      which reduce the quality of their lives.

PMID- 16458823
TI  - Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancy.
AB  - Mutations in the voltage-gated sodium channel gene SCN1A are a major cause of
      severe myoclonic epilepsy of infancy (Dravet syndrome) and generalized epilepsy
      with febrile seizures plus. This study reports the identification of six de novo
      SCN1A mutations in patients with severe myoclonic epilepsy of infancy, including
      a tetranucleotide deletion in exon 26. The same deletion was previously observed
      in two unrelated patients and appears to result from slipped-strand mispairing of
      a direct repeat during deoxyribonucleic acid replication. Review of the
      literature indicates that recurrent mutations account for 25% of SCN1A mutations
      in severe myoclonic epilepsy of infancy, including six sites of deamination at
      CpG dinucleotides.

PMID- 16458824
TI  - Febrile seizures in southern Chinese children: incidence and recurrence.
AB  - This study investigates the incidence, recurrence, and risk factors of febrile
      seizures in southern Chinese children. A retrospective study of a 5-year period
      (March 1998 through February 2003) was conducted for all children admitted with
      first febrile seizure to a university teaching hospital of Hong Kong, serving a
      population of 31,700 under 6 years. A total of 565 Chinese children (329 males,
      236 females) were identified with mean age of 2.1 +/- 1.1 years. The annual
      incidence was 0.35%. Among them 16% (91/565) had complex febrile seizures. Family
      history of febrile and afebrile seizures was present in 17.5% and 2.7%
      respectively. The mean follow-up period was 2.33 +/- 1.69 years. Altogether 103
      children (18%) had recurrence, and the cumulative rates by 1, 2, and 3 years were
      12.7%, 18.7%, and 20.5% respectively. Three significant factors were identified
      for higher risk of recurrence: early age of onset, family history of febrile
      seizure, and complex febrile seizure. The incidence of first febrile seizure in
      Chinese children is low compared with the Western world and relatively similar to
      mainland China. Recurrence is also lower despite similarities in the predictive
      factors. Further epidemiologic and genetic studies will be necessary to confirm
      and explain this interethnic variation.

PMID- 16458825
TI  - Peripheral neuropathy in genetic mitochondrial diseases.
AB  - Peripheral neuropathy is an underrecognized but common occurrence in genetic
      mitochondrial disorders. To gain insight into the frequency and clinical
      presentation of this complication, nerve conduction studies were performed on 43
      subjects with congenital lactic acidosis enrolled in a controlled clinical trial
      of oral dichloroacetate. Median and peroneal motor conduction studies and median
      and sural sensory conduction studies were performed on each patient. The mean
      amplitude of the peroneal motor nerve (P < 0.001) and the conduction velocities
      of the median (P < 0.001) and peroneal (P < 0.001) motor nerves were uniformly
      lower in our subjects than in healthy literature control subjects. There were no
      significant differences in sensory nerve conduction studies. A generalized
      reduction in motor nerve conduction velocity was the dominant
      electrophysiological abnormality in the patients in this study and was
      independent of age, sex, or congenital mitochondrial disorder. We postulate that
      cellular energy failure is the most likely common cause of peripheral neuropathy
      in patients with genetic mitochondrial diseases, owing to the high demand for
      adenosine triphosphate via aerobic carbohydrate metabolism by nerve tissue.

PMID- 16458826
TI  - Neonatal rigid-akinetic syndrome and dentato-olivary dysplasia.
AB  - This report describes a male infant who presented since birth with rigidity and
      hypokinesia. Severe developmental delay, episodic central hypoventilation, and
      drug-resistant epilepsy progressively added to the extrapyramidal signs in the
      following months and led to the patient's death at 10 months of age.
      Neuroradiologic and neurometabolic evaluations were negative. Normal
      cerebrospinal metabolites excluded a defect in dopamine metabolism, and treatment
      with levodopa failed to improve his motor symptoms. Neuropathologic findings
      demonstrated dentato-olivary dysplasia. While isolated dentato-olivary dysplasia
      has been described in a few cases of Ohtahara syndrome, to our knowledge, the
      association with infantile parkinsonism has not been previously reported.

PMID- 16458827
TI  - Mirror movements following cortical resection of polymicrogyria in a child with
      intractable epilepsy.
AB  - Mirror movements may be congenital or acquired. There are few reports of acquired
      mirror movements in pediatric patients. Further, mirror movements in children
      with epilepsy have rarely been reported. A 9-year old male, with intractable
      partial epilepsy resulting from polymicrogyria of the right hemisphere, underwent
      cortical resection of the right frontotemporoparietal region for a malformation
      of cortical development. He developed left hemiplegia and mirror movements in the
      left hand in the postoperative period. Four months after surgery, he remained
      seizure-free with mild residual left-sided hemiplegia and persistent mirror
      movements. Mechanisms postulated for mirror movements include aberrant pyramidal
      tract development and transcallosal inhibitory pathways. The latter mechanism
      might have contributed to the mirror movements observed in this child. This study
      is the first report of mirror movements following focal cortical resection for
      intractable epilepsy due to polymicrogyria.

PMID- 16458828
TI  - Expanding the clinical picture of Simpson-Golabi-Behmel syndrome.
AB  - This report describes a 14-year-old male with Simpson-Golabi-Behmel overgrowth
      syndrome. He was born via cesarean section because of macrocephaly and
      subsequently exhibited significant developmental delay in motor, language, and
      cognitive skills with mental retardation and epilepsy. He manifests the
      characteristic dysmorphic ("bulldog") facial features of Simpson-Golabi-Behmel
      syndrome. His molecular genetic testing has substantiated the clinical diagnosis
      of Simpson-Golabi-Behmel syndrome; however, he is unique in that he has mental
      retardation, hydrocephalus, and epilepsy, which have not been previously
      documented in Simpson-Golabi-Behmel syndrome in the literature.

PMID- 16458829
TI  - Extensive Mongolian spots: a clinical sign merits special attention.
AB  - Although typical and limited Mongolian spots are benign skin markings at birth
      which fade and disappear as the child grows, extensive Mongolian spots deserve
      special attention as possible indications of associated inborn error of
      metabolism. A few cases of extensive Mongolian spots in association with
      inheritable storage diseases have been reported. Some hypotheses have been put
      forward, but further investigation is necessary to elucidate the causative
      factors. This report describes three infants with generalized Mongolian spots,
      two infants with GM1 gangliosidosis type 1, and one in association with Hurler
      syndrome. Findings of generalized Mongolian spots in newborns may lead to an
      early detection and early treatment before irreversible organ damage occurs.

PMID- 16458830
TI  - Misleading effects of clonazepam in symptomatic electrical status epilepticus
      during sleep syndrome.
AB  - Electrical status epilepticus during sleep syndrome and its variants are age
      dependent epileptic encephalopathies associated with a sleep-related
      electroencephalographic pattern of continuous spike-waves, combined with motor or
      cognitive impairment. These epileptic encephalopathies are usually not responsive
      to conventional antiepileptic drugs. This report describes two children in whom
      clonazepam had no effect on cognitive and motor disorders but controlled spike
      activity, preventing a proper diagnosis. Withdrawal of clonazepam was accompanied
      by the recurrence of continuous spike-waves in slow sleep, permitting the
      diagnosis of electrical status epilepticus during sleep syndrome and appropriate
      therapeutic decisions. These two cases of the misleading effect of clonazepam in
      electrical status epilepticus during sleep syndrome illustrate the puzzling
      situation that can occur when therapeutic options only consider the
      electroencephalographic features without prior syndromic diagnosis.

PMID- 16458831
TI  - Magnetic resonance spectroscopy and electroencephalography in baclofen coma.
AB  - This report describes a 14-year-old female who presented with coma and seizures.
      Continuous electroencephalographic monitoring revealed suppression and
      semiperiodic sharp waves. Magnetic resonance spectroscopy performed 1 day after
      admission suggested a good outcome despite her clinical examination and
      electroencephalogram. She was subsequently found to have elevated serum baclofen
      levels after an intentional overdose. At the time of her discharge from the
      pediatric intensive care unit, she manifested no neurologic deficits, and on
      telephone follow-up 2 years after the ingestion the patient had no complaints of
      any cognitive problems or neurologic dysfunction.

PMID- 16458832
TI  - Neuropathology of methylmalonic acidemia in a child.
AB  - Methylmalonic acidemia is a rare disease, and its neuropathology in childhood has
      been rarely reported. A 3-year-old male with vitamin B12 nonresponsive type of
      methylmalonic acidemia developed repeated attacks of acidemia associated with
      common cold since neonatal age. Psychomotor development was markedly delayed, and
      he died of a severe attack of acidemia. Postmortem examination disclosed marked
      brain atrophy with old lesions of hypomyelination, granule cell reduction, and
      spongy changes scattered in the cerebral cortex, white matter, brainstem nuclei,
      and cerebellar cortex, and accompanied by recent lesions of multiple small
      hemorrhagic and necrotic foci in the caudate nucleus, cerebellum, and brainstem.
      Neuron reduction without astrogliosis in the cerebellum, brainstem, and
      hippocampus, and the association of single-stranded DNA-positive cells in the
      brainstem and cerebellar nuclei were demonstrated. These findings, and
      karyorrhexis in the neonatal brains described in the literature, suggest that
      repeated episodes of cell death with apoptosis occur in association with attacks
      of acidosis beginning in the neonatal period in methylmalonic acidemia.

PMID- 16458833
TI  - Acute necrotizing encephalopathy associated with human herpesvirus-6 infection.
AB  - An extremely rare case of acute necrotizing encephalopathy caused by human
      herpesvirus-6 variant type B infection is reported. The patient, a 14-month-old
      previously healthy female, presented with high fever and generalized tonic
      convulsion followed by rapid deterioration of consciousness. On the second day of
      the illness, the protein level of the cerebrospinal fluid increased without
      pleocytosis. On the third day, magnetic resonance images demonstrated symmetric,
      abnormal signal intensity lesions in the bilateral thalamus, cerebellum, and
      brainstem. On the fourth day, characteristic maculopapular rash of exanthema
      subitum appeared on the trunk. Human herpesvirus-6 deoxyribonucleic acid was
      detected by the polymerase chain reaction in the serum, and immunoglobulin G and
      immunoglobulin M of serum human herpesvirus-6 were positive. On the twelfth day
      of illness, the patient died as a result of severe brain damage. Acute
      necrotizing encephalopathy should be included in the differential diagnosis when
      examining infants and young children with fulminating consciousness disturbance
      and intractable convulsion. In addition, as a causative virus, human herpesvirus
      6 has to be considered at the pre-eruptive stage of exanthema subitum. Magnetic
      resonance images are useful because they reveal the characteristic distribution
      of lesions specific to acute necrotizing encephalopathy.

PMID- 16458834
TI  - Folinic acid-responsive seizures initially responsive to pyridoxine.
AB  - This report presents a male who developed clonic seizures on the day he was born.
      The next day, the diagnosis of pyridoxine-dependent seizures was made. However,
      contradictory to this diagnosis, seizures reappeared despite treatment with
      pyridoxine. Seizures ceased after folinic acid was initiated. The clinical and
      biochemical characteristics of folinic acid-responsive seizures are reviewed.
      Treatment with folinic acid should be considered in neonatal seizures of unknown
      origin that do not respond to pyridoxine, or manifest a transient response to
      pyridoxine.

PMID- 16458835
TI  - Corticosteroids in the treatment of acute Sydenham's chorea.

PMID- 16458836
TI  - A new mutation of IGHMBP2 gene.

PMID- 16458838
TI  - Moderate hypothermia in neonatal encephalopathy.

PMID- 16458840
TI  - Nephron-sparing surgery in children with primary renal tumor: indications and
      results.
AB  - Nephron-sparing surgery (NSS) is the treatment of choice for children with
      bilateral Wilms' tumor (WT), or with WT on a single kidney, or with WT and a
      disease of the contralateral kidney, or with benign kidney tumor. NSS is a
      reasonable alternative to nephrectomy in children at risk of metachronous WT,
      including children with genetic syndromes, children younger than 1 year of age,
      and children with hyperplastic nephroblastomatosis. The use of NSS in selected
      children with "low-risk" or stage I "intermediate-risk" WT and a normal
      contralateral kidney is still controversial. Available data suggest that, in
      children with WT, NSS does not impair the outcome and has a renal function
      advantage over nephrectomy.

PMID- 16458841
TI  - Perinatal neuroblastoma.
AB  - One-fifth of all neuroblastomas are diagnosed either antenatally or in the first
      3 months of life. Over the past two decades, routine prenatal ultrasound has
      significantly increased the rate of diagnosis of fetal neuroblastoma. More than
      90% of these tumors arise in the adrenal gland, suggesting a link between
      perinatal tumors and the nodular collections of neuroblasts that are part of
      normal adrenal development. In fact, there is compelling evidence that the cystic
      variant of perinatal neuroblastoma is caused by a perturbation of the involution
      program of these neuroblastic nodules. The vast majority of these cases are
      localized tumors with favorable biological features, which correlates with a 4
      year survival of greater than 95%. The high rate of spontaneous regression of
      these tumors, coupled with the significant risks of resectional surgery in small
      neonates, has prompted the development of a prospective clinical trail of
      expectant observation as primary therapy for infants with small, localized
      tumors. The ultimate goal of such studies is to define an ultra-low-risk group of
      neuroblastoma patients who do not require invasive procedures or chemotherapy to
      achieve an excellent outcome.

PMID- 16458842
TI  - Management of liver tumors in childhood.
AB  - Primary neoplasms of the liver occur rarely during childhood and constitute only
      0.3-2% of all pediatric tumors. However, they comprise a variety of entities
      including benign and malignant epithelial, as well as mesenchymal tumors, the
      most common of these being hepatoblastoma and hepatocellular carcinoma. Clinical
      presentation, especially in young children is relatively uniform with abdominal
      enlargement and a painless tumor, and often specific symptoms develop late.
      Prerequisites for clinical diagnosis are a comprehensive laboratory workup and
      good quality imaging mainly with ultrasound, as well as CT and/or MRI scans.
      Histological diagnosis is essential for differential diagnosis and may only be
      omitted in some hepatoblastoma patients of the typical age (6 months to 3 years)
      with an excessively elevated serum-alpha-fetoprotein. Surgery is the mainstay of
      treatment for all benign and malignant liver tumors. Hepatoblastomas mostly
      respond well to chemotherapy. Therefore, this modality should always be combined
      with surgical resection in these patients and in many cases can reduce the size
      of a large tumor to resectability. Prognosis nowadays usually is good in all
      benign tumors and hepatoblastoma, as well as in some other rare malignancies, but
      dismal in hepatocellular carcinoma and other chemotherapy non-sensitive malignant
      tumors.

PMID- 16458843
TI  - Management of osteosarcoma pulmonary metastases.
AB  - Although there has been considerable improvement in survival among children with
      osteosarcoma over the past 30 years, patients with metastatic disease fare very
      poorly. The best-case scenario for metastatic patients is a survival rate of 30%
      assuming complete resection of lung metastases without other disease. To achieve
      this optimal outcome, an aggressive surgical approach is recommended in which all
      metastatic disease is resected. This includes metastatic foci that are detected
      by imaging as well as those only identified by palpation at thoracotomy.
      Investigation into the biology of the metastatic process of osteosarcoma as well
      as in identification of molecular features that correlate with prognosis is very
      active and will likely yield important findings that will impact therapy in the
      future. An area of investigation that remains needed is the prospective
      evaluation of the surgical management of these patients with the goal of
      critically evaluating the impact of the various surgical strategies on patient
      outcome measures, such as disease-recurrence and survival.

PMID- 16458844
TI  - Malignant germ cell tumors in childhood.
AB  - Malignant germ cell tumors are a very heterogeneous group of neoplasms that have
      historically carried a poor prognosis. A review of the cooperative studies on
      malignant extracranial germ cell tumors in children was performed to update the
      progress in treatment and outcome for this rare group of tumors. The advent of
      platinum-based chemotherapy in the 1980s dramatically improved the prognosis for
      these tumors and allowed redefinition of risk groups. Chemotherapy regimens have
      been sequentially modified to reduce toxicity while maintaining survival.
      Surgical management has evolved from an aggressive en bloc resection at diagnosis
      to a more tailored approach, with resection and meticulous staging for low stage
      tumors at diagnosis and biopsy with neoadjuvant chemotherapy for advanced stage
      tumors. Improved surgical margins and prognosis are seen in post chemotherapy
      resections for high stage tumors. Large persisting masses after chemotherapy are
      often due to coexisting elements of benign teratoma, and aggressive attempts at
      resection are warranted in these patients with expectation of successful outcome.

PMID- 16458845
TI  - Gastrointestinal tumors in children and adolescents.
AB  - Tumors of the pediatric gastrointestinal tract are extremely rare. Their
      infrequent presentation at treatment centers has not allowed for the development
      of standardized treatment protocols and prospective review. The most prevalent
      gastrointestinal neoplasms and malignancies are described, including
      gastrointestinal lymphoma, colorectal carcinoma, carcinoid tumors,
      gastrointestinal stromal tumors, leiomyomas, juvenile polyps, inflammatory
      pseudotumors, gastric tumors, and Peutz-Jeghers polyposis syndrome. Current
      recommendations for the medical and surgical management of these tumors are
      reviewed and summarized for this vast group of gastrointestinal neoplasms in
      children.

PMID- 16458846
TI  - Malignant adrenal tumors.
AB  - Adrenal tumors, apart from neuroblastoma, are relatively rare in infancy and
      childhood. Most adrenal lesions are benign, and both benign and malignant tumors
      may be hormonally active thus, making accurate preoperative diagnosis difficult.
      The two main malignant tumors are adrenocortical carcinoma and pheochromocytoma.
      In both tumors, it may be difficult to determine benign from malignant and the
      biologic behavior and degree of invasion may portend a more malignant course.
      Surgical excision is the primary therapy for both tumors, including excision of
      metastatic and recurrent tumor. An open procedure should be considered for
      invasive adrenocortical carcinoma and in pheochromocytomas in which preoperative
      imaging demonstrates metastatic nodal disease. A laparoscopic approach is
      preferred for lesions in which preoperative imaging demonstrates a localized
      lesion. Chemotherapy, although without proven efficacy, is utilized in some
      children with metastatic or unresectable disease.

PMID- 16458847
TI  - Childhood rhabdomyosarcoma.
AB  - A malignant tumor of striated muscle origin, Rhabdomyosarcoma (RMS) is a
      childhood tumor that has benefited from nearly 30 years of multimodality therapy
      culminating in a greater than 70% overall current 5-year survival. Prognosis for
      RMS is dependent on anatomic primary tumor site, age, completeness of resection,
      presence and number of metastatic sites, histology, and biology of the tumor
      cells. Multimodality treatment is based on risk stratification according to
      pretreatment stage, postoperative group, histology, and site. Therefore,
      pretreatment staging is vital for assessment and is dependent on primary tumor
      site, size, regional lymph node status, and presence of metastases. Unique to RMS
      is the concept of postoperative clinical grouping that assesses the completeness
      of disease resection and takes into account lymph node evaluation both at the
      regional and metastatic basins. At all sites, if operative resection of all
      disease is accomplished, including microscopic disease, survival is improved.
      Therefore, the surgeon plays a vital role in determining risk stratification for
      treatment and local control of the primary tumor for RMS. The current state of
      the art treatment is based on treatment protocols developed by the Soft Tissue
      Sarcoma Committee of the Children's Oncology Group.

PMID- 16458848
TI  - Endogenous versus exogenous attentional cuing effects on memory.
AB  - Three experiments were conducted to investigate the influence of early
      attentional cuing effects on subsequent memory. In an incidental study phase, a
      cue preceded two simultaneously displayed words. An endogenous cue (row of arrows
      pointing toward one word) or an exogenous cue (row of stars at the location of
      one word) indicated which word to read aloud. In a subsequent test phase, memory
      for these cued and uncued words was measured. In Experiment 1, these attentional
      manipulations had almost no effect on subsequent implicit memory measured using a
      speeded reading (naming) test. Experiments 2 and 3 demonstrated that, on an
      explicit memory test, words were reliably better recognized in the endogenous
      condition than in the exogenous condition. These results suggest that endogenous
      attentional cues promote more active processing and hence elaboration of words,
      assisting their subsequent conscious retrieval.

PMID- 16458849
TI  - [Evidence-based analysis of prophylactic abdominal drainage].
AB  - Abdominal prophylactic drainage in digestive surgery was considered until
      recently as a dogma. But randomised controlled trials have questioned the routine
      use of abdominal drain in elective surgery. The aim of this review was to assess
      the usefulness of abdominal prophylactic drainage according to the concept of
      evidence-based medicine by analysing published randomised trials and meta
      analyses. Levels of evidence vary greatly according to the type of surgery. One
      can conclude: with a good level of evidence that abdominal drainage has no place
      following elective cholecystectomy, appendicectomy and colectomy with
      intraperitoneal anastomosis; that it is perhaps unwarranted (lower level of
      evidence) following gastroduodenal surgery, pancreatectomy, splenectomy, and
      rectal surgery; and finally that could be indicated following oesophagectomy and
      common bile duct surgery (very low level of evidence). Nevertheless, when
      interpreting these data and evidence-based guidelines we should be consider the
      limitations of published studies (series coming from very expert teams, selected
      patients, short series, and elective surgery).

PMID- 16458850
TI  - Rabbit small intestine does not contain an annexin II/caveolin 1 complex as a
      target for 2-azetidinone cholesterol absorption inhibitors.
AB  - Intestinal cholesterol absorption is specifically inhibited by the 2-azetidinone
      cholesterol absorption inhibitor ezetimibe. Photoreactive ezetimibe analogues
      specifically label a 145-kDa protein in the brush border membrane of enterocytes
      from rabbit small intestine identified as aminopeptidase N (CD13). In zebrafish
      and mouse small intestinal cytosol, a heterocomplex of M(r) 52 kDa between
      annexin II and caveolin 1 was suggested as a target of ezetimibe. In contrast, in
      the cytosol and brush border membrane vesicles (BBMV) from rabbit small intestine
      of control animals or rabbits treated with the nonabsorbable cholesterol
      absorption inhibitor AVE 5530, both annexin II and caveolin 1 were exclusively
      present as monomers without any heterocomplex formation. Upon immunoprecipitation
      with annexin II a 52-kDa band was observed after immunostaining with annexin II
      antibodies, whereas no staining of a 52-kDa band occurred with anti-caveolin 1
      antibodies. Vice versa, a 52-kDa band obtained by immunoprecipitation with
      caveolin 1 antibodies did not stain with annexin II-antibodies. The intensity of
      the 52-kDa band was dependent on the amount of antibody and was also observed
      with anti-actin or anti-APN antibodies suggesting that the 52-kDa band is a
      biochemical artefact. After incubation of cytosol or BBMV with radioactively
      labelled ezetimibe analogues, no significant amounts of the ezetimibe analogues
      could be detected in the immunoprecipitate with caveolin-1 or annexin II
      antibodies. Photoaffinity labelling of rabbit small intestinal BBMV with
      ezetimibe analogues did not result in labelling of proteins being immunoreactive
      with annexin II, caveolin 1 or a 52-kDa heterocomplex. These findings indicate
      that the rabbit small intestine does not contain an annexin II/caveolin 1
      heterocomplex as a target for ezetimibe.

PMID- 16458851
TI  - Operationalizing the "vulnerability" and "stress" components of the hopelessness
      theory of depression: a multi-wave longitudinal study.
AB  - The current study tested of the diathesis-stress component of the hopelessness
      theory (HT) using (1) a "weakest link" approach towards operationalizing
      vulnerability (e.g., an individual is as vulnerable to depression as his/her most
      depressogenic inferential style-DIS) and (2) an idiographic approach towards
      operationalizing high levels of stress. The procedure involved an initial
      assessment during which participants completed measures assessing DISs and
      depressive symptoms. The procedure also involved a series of eight follow-up
      assessments, occurring every 6 weeks, during which depressive symptoms and
      hassles were assessed. Hypotheses were tested in two samples of adults (i.e.,
      adults diagnosed with a current MDE and adults diagnosed with a past MDE at Time
      1). In line with hypotheses, in both samples, depressogenic weakest links were
      associated with greater elevations in depressive symptoms following elevations in
      hassles. At the same time, equally strong support was obtained for the HT when
      stress was operationalized from a nomothetic perspective and when vulnerability
      was operationalized as a DIS about causes (but not consequences or self).

PMID- 16458852
TI  - The post-event processing questionnaire in a clinical sample with social phobia.
AB  - Post-event processing (PEP) involving rumination about perceived inadequacy in a
      past social situation has been proposed as an important maintaining factor in
      social phobia. The three aims of this study were to examine (a) the factor
      structure and internal reliability of a modified version of the Post-Event
      Processing Questionnaire [Rachman, S., Gruter-Andrew, J., & Shafran, R. (2000).
      Post-event processing in social anxiety. Behaviour Research and Therapy, 38, 611
      617] in a clinical sample with social phobia (N=117), (b) the associations
      between PEP and symptoms of anxiety and depression, and (c) the relationship
      between perspective-taking ('field' and 'observer') and anxiety. Principal axis
      factor analysis yielded a highly reliable one-factor solution in our clinical
      sample, which generally replicated Rachman et al.'s findings with a sample of
      undergraduate students. PEP was most strongly and independently associated with
      state anxiety when depression, general anxiety and stress were controlled for.
      Contrary to expectations, PEP was not related to measures of social anxiety. The
      relationship between perspective-taking and anxiety was more complex than
      expected. Theoretical implications of these findings are discussed with reference
      to contemporary cognitive-behavioural models of social phobia.

PMID- 16458853
TI  - Self-administered behavioural family intervention for parents of toddlers:
      effectiveness and dissemination.
AB  - This study examined the effectiveness of a self-administered behavioural family
      intervention (BFI) for parents of toddlers, within the context of a regular
      telephone counselling service provider. Telephone counsellors were trained in the
      delivery of BFI, and 110 mothers of toddlers completed the intervention. There
      were significant short-term effects of intervention in terms of child behaviour
      problems and parenting style, parenting confidence and anger. In addition, there
      were improvements in mother's personal adjustment, and lower levels of parenting
      conflict. The intervention effects were maintained at 3-month follow-up. The
      results provide support for the effectiveness of self-administered BFI, and have
      implications for the population level delivery of behavioural family
      interventions.

PMID- 16458854
TI  - Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to
      variable penetrance in hearing impairment.
AB  - Mutations in the mitochondrial DNA are one of the most important causes of
      sensorineural hearing loss, especially in the 12S ribosomal RNA (rRNA) gene. We
      have analyzed the mtDNA 12S rRNA gene in a cohort of 443 families with hearing
      impairment, and have identified the A1555G mutation in 69 unrelated cases. A1555G
      is not a fully penetrant change, since only 63% of subjects with this change have
      developed hearing impairment. In addition, only 22% of the 183 A1555G deaf
      subjects were treated with aminoglycosides. Two novel nucleotide changes (T1291C
      and T1243C) were identified. T1243C was found in five deafness cases and one
      control sample. Mutation T1291C was detected in all maternally related
      individuals of a pedigree and in none of 95 control samples. Conservation
      analysis and comparison of the 12S rRNA structure with the 16S rRNA of
      Escherichia coli showed that the T at nucleotide 1243 and A at nucleotide 1555
      are conserved positions. Prediction of RNA secondary structure showed changes in
      all 12S rRNA variants, the most severe being for T1291C. The reported data
      confirm the high prevalence of mutation A1555G in deafness cases and the major
      role of the 12S rRNA gene in hearing. The two novel changes reported here might
      have different contributions as deafness-related variants. T1291C fulfills the
      criteria of a disease-causing change. As in the case of mutation A1555G, the
      underlying phenotype of T1291C is not homogeneous for all family members,
      providing evidence for the implication of environmental and/or additional genetic
      factors.

PMID- 16458855
TI  - The Plasmodium vivax rhoptry-associated protein 1.
AB  - Rhoptries are cellular organelles localized at the apical pole of apicomplexan
      parasites. Their content is rich in lipids and proteins that are released during
      target cell invasion. Plasmodium falciparum rhoptry-associated protein 1 (RAP1)
      has been the most widely studied among this parasite species' rhoptry proteins
      and is considered to be a good anti-malarial vaccine candidate since it displays
      little polymorphism and induces antibodies in infected humans. Monoclonal
      antibodies directed against RAP1 are also able to inhibit target cell invasion in
      vitro and protection against P. falciparum experimental challenge is induced when
      non-human primates are immunized with this protein expressed in its recombinant
      form. This study describes identifying and characterizing RAP1 in Plasmodium
      vivax, the most widespread parasite species causing malaria in humans, producing
      more than 80 million infections yearly, mainly in Asia and Latin America. This
      new protein is encoded by a two-exon gene, is proteolytically processed in a
      similar manner to its falciparum homologue and, as observed by microscopy, the
      immunofluorescence pattern displayed is suggestive of its rhoptry localization.
      Further studies evaluating P. vivax RAP1 protective efficacy in non-human
      primates should be carried out taking into account the relevance that its P.
      falciparum homologue has as an anti-malarial vaccine candidate.

PMID- 16458856
TI  - Two forms of human Inscuteable-related protein that links Par3 to the Pins
      homologues LGN and AGS3.
AB  - In cell polarization of Drosophila neuroblasts, Inscuteable (Insc) functions via
      tethering Partner of Insc (Pins) to Bazooka, homologous to human cell polarity
      protein Par3. However, little has been known about mammalian homologues of Insc.
      Here we describe cloning of two distinct cDNAs from human Insc gene, which is
      differentially expressed from alternative first exons: one encodes 579 amino
      acids, whereas the other lacks the N-terminal 47 amino acids. In contrast to
      human homologues for Pins and Par3, human Insc exhibits a weak homology with the
      Drosophila counterpart. Nevertheless, human Insc proteins bind to the human Pins
      homologues LGN and AGS3, and also to human Par3 and its related protein Par3beta.
      Although LGN by itself is incapable of interacting with Par3, coexpression of
      human Insc leads to the interaction between LGN and Par3, indicating that human
      Insc plays an evolutionarily conserved role as an adaptor protein that links Pins
      to Par3.

PMID- 16458857
TI  - Crystallizing new approaches for antimicrobial drug discovery.
AB  - Over the past decade, the sequences of microbial genomes have accumulated,
      changing the strategies for the discovery of novel anti-infective agents. Targets
      have become plentiful, yet new antimicrobial agents have been slow to emerge from
      this effort. In part, this reflects the long discovery and development times
      needed to bring new drugs to market. In addition, bottlenecks have been revealed
      in the antimicrobial drug discovery process at the steps of identifying good
      leads, and optimizing those leads into drug candidates. The fruit of structural
      genomics may provide opportunities to overcome these bottlenecks and fill the
      antimicrobial pipeline, by using the tools of structure guided drug discovery
      (SGDD).

PMID- 16458858
TI  - Histamine H2 receptor overexpression induces U937 cell differentiation despite
      triggered mechanisms to attenuate cAMP signalling.
AB  - Knowing that cell-surface receptors that recognize and respond to extracellular
      stimuli are key components for the regular communication between individual cells
      required for the survival of any living organism, the aim of the present work was
      to investigate the effect of H2R overexpression on the U937 signal transduction
      pathway and its consequences on cell proliferation and differentiation. The
      overexpression of H2R led to an increase in cAMP basal levels, a leftward shift
      of agonist concentration-response curves, and similar maximal response to agonist
      treatment, suggesting that overexpressed H2Rs act as functional spare receptors.
      In this system cells triggered several mechanisms tending to restore cAMP basal
      levels to those of the naive cells. H2R overexpression induced PDE activity
      stimulation and GRK2 overexpression. In spite of the onset of these regulatory
      mechanisms, H2 agonist and rolipram treatments induced the terminal
      differentiation of the H2R overexpressed clone, conversely to the naive cells.
      Present findings show that stably H2R overexpression alters cAMP signalling as
      the result of not only the amounts of second messenger generated but also the
      activation or upregulation of various components of signalling cascade, leading
      to an adapted biologically unique system. This adaptation may represent an
      advantage or a disadvantage, depending on the biological system, but in any case,
      the existence of compensatory mechanisms should be considered when a clinical
      treatment is designed.

PMID- 16458859
TI  - Cytotoxic efficacy of an anthraquinone linked platinum anticancer drug.
AB  - Platinum complexes are widely used in cancer chemotherapy; however, they are
      associated with toxicity, high "non-specific" reactivity and relatively poor
      pharmacokinetic profiles. In particular, their low cellular uptake and rapid
      metabolic inactivation means that the amount of "active" drug reaching the
      nuclear compartment is low. Our strategy to facilitate nuclear accumulation was
      to introduce a hydrophobic anthraquinone (1C3) moiety to the Pt-complex.
      Anthraquinones are known to readily intercalate into DNA strands and hence, the
      Pt-1C3 complex may represent an effective system for the delivery of the platinum
      moiety to nuclear DNA. Efficacy of the complex was determined by measuring the
      extent and potency of cytotoxicity in comparison to cisplatin and an
      anthraquinone based anticancer drug, doxorubicin. The Pt-1C3 complex generated
      higher levels of cytotoxicity than cisplatin, with a potency of 19 +/- 4 microM
      in the DLD-1 cancer cell line. However, this potency was not significantly
      different to that of the 1C3 moiety alone. To examine the reason for the apparent
      lack of platinum related cytotoxicity, the cellular distribution was
      characterised. Confocal fluorescence microscopy indicated that the Pt-1C3 complex
      was rapidly sequestered into lysosomes, in contrast to the nuclear localisation
      of doxorubicin. In addition, there was negligible DNA associated Pt following
      administration of the novel complex. Thus, the addition of a 1C3 moiety generated
      sequestration of the complex to lysosomes, thereby preventing localisation to the
      nucleus.

PMID- 16458860
TI  - The emotional power of music: how music enhances the feeling of affective
      pictures.
AB  - Music is an intriguing stimulus widely used in movies to increase the emotional
      experience. However, no brain imaging study has to date examined this enhancement
      effect using emotional pictures (the modality mostly used in emotion research)
      and musical excerpts. Therefore, we designed this functional magnetic resonance
      imaging study to explore how musical stimuli enhance the feeling of affective
      pictures. In a classical block design carefully controlling for habituation and
      order effects, we presented fearful and sad pictures (mostly taken from the IAPS)
      either alone or combined with congruent emotional musical excerpts (classical
      pieces). Subjective ratings clearly indicated that the emotional experience was
      markedly increased in the combined relative to the picture condition.
      Furthermore, using a second-level analysis and regions of interest approach, we
      observed a clear functional and structural dissociation between the combined and
      the picture condition. Besides increased activation in brain areas known to be
      involved in auditory as well as in neutral and emotional visual-auditory
      integration processes, the combined condition showed increased activation in many
      structures known to be involved in emotion processing (including for example
      amygdala, hippocampus, parahippocampus, insula, striatum, medial ventral frontal
      cortex, cerebellum, fusiform gyrus). In contrast, the picture condition only
      showed an activation increase in the cognitive part of the prefrontal cortex,
      mainly in the right dorsolateral prefrontal cortex. Based on these findings, we
      suggest that emotional pictures evoke a more cognitive mode of emotion
      perception, whereas congruent presentations of emotional visual and musical
      stimuli rather automatically evoke strong emotional feelings and experiences.

PMID- 16458862
TI  - Fluoro-Ruby labeling prior to an amphetamine neurotoxic insult shows a definitive
      massive loss of dopaminergic terminals and axons in the caudate-putamen.
AB  - Fluoro-Ruby (FR) was injected into the substantia nigra (SNc) to label
      dopaminergic axons and terminals in the caudate putamen (CPu) of rats 7 days
      prior to a neurotoxic d-amphetamine (AMPH) exposure. Three days after AMPH
      exposure, a massive loss in the TH immunoreactive (TH(+)) axons and terminals was
      seen in the CPu. The FR-labeled (FR(+)) axons and terminals in the CPu were
      greatly diminished with those remaining being enlarged or swollen after AMPH.
      Fluoro-Jade C (FJ-C) labeling was used to verify AMPH-induced axonal and terminal
      degeneration. This study demonstrates that fluorescent anterograde tract tracers
      can be used to show the subsequent axonal and terminal degeneration after
      systemic exposures to toxins and provides direct evidence that CPu axons and
      terminals from SNc dopaminergic neurons can be destroyed after neurotoxic
      exposure to AMPH.

PMID- 16458861
TI  - A comparison of hyperbaric oxygen versus hypoxic cerebral preconditioning in
      neonatal rats.
AB  - The potency of hyperbaric preconditioning (HBO-PC) is uncertain compared to well
      validated ischemic or hypoxic models and no studies have directly compared HBO-PC
      to hypoxic preconditioning (HPC). We subjected rat pups to unilateral carotid
      cauterization followed by 90 min (min) of hypoxia using 8% O(2). Three HBO-PC
      regimes (maximum 2.5 atmospheres for 150 min) were compared to HPC (150 min of 8%
      O(2)) for changes in mortality and brain weight. Preconditioning-induced
      oxidative stress was assessed using aconitase activity and manganese superoxide
      dismutase (MnSOD) transcript levels. Initial brain weight data revealed a large
      coefficient of variation and compelled an examination of the temperature
      sensitivity of the model that revealed a narrow optimal range of 35 to 37 degrees
      C of variability in brain injury and mortality. With rigorous temperature
      control, high dose HBO-PC and HPC showed comparable anatomic (mean hemispheric
      weight decrease: control 42%, HPC 25% (P=0.01), HBO-PC 26% (P=0.01) and mortality
      protection (control 14.7%, HPC 5.9% HBO-PC 5.7%, P=0.001). High dose HBO-PC, but
      not HPC, suppressed aconitase activity by 65% at 24 h after the preconditioning
      stimulus (P=0.001). In contrast, MnSOD mRNA increased 2.5-fold at 24 h after HPC
      (P=0.007) but not after high dose HBO-PC. Thus, when temperature variability is
      eliminated, HBO-PC and HPC elicit similar preconditioning efficacy in neonatal
      brain but invoke different defenses against oxidative stress.

PMID- 16458863
TI  - Leukemia inhibitory factor is a key regulator of astrocytic, microglial and
      neuronal responses in a low-dose pilocarpine injury model.
AB  - Insult to the central nervous system (CNS) induces many changes, including
      altered neurotransmitter expression, activation of astrocytes and microglia,
      neurogenesis and cell death. Cytokines and growth factors are candidates to be
      involved in astrocyte and microglial activation, and the up-regulation of glial
      fibrillary acidic protein (GFAP) is associated with brain damage. One of these
      candidates is leukemia inhibitory factor (LIF), a pro-inflammatory cytokine that
      is induced in astrocytes by brain damage or seizure. LIF also regulates
      expression of both neuropeptide Y (NPY) and galanin following peripheral nerve
      injury. To test the hypothesis that LIF regulates astrocyte, microglial and
      neuropeptide responses to a mild insult, we used a low-dose pilocarpine model to
      induce a brief seizure in LIF knock-out (KO) mice. Compared to wild type mice,
      the LIF KO mouse displays reduced astrocyte and microglial activation in the
      hippocampus. In addition, LIF KO mice display dramatically altered NPY, but not
      galanin, expression in response to injury. Thus, LIF is required for normal glial
      responses to brain damage, and, as in the periphery, LIF regulates NPY expression
      in the CNS.

PMID- 16458865
TI  - Cell wall teichoic acids of streptomycetes of the phenetic cluster 'Streptomyces
      fulvissimus'.
AB  - Structures of the anionic polymers of streptomycetes Streptomyces fulvissimus VKM
      Ac-994(T), Streptomyces longispororuber VKM Ac-1735(T), Streptomyces
      aureoveticillatus VKM Ac-48(T) and Streptomyces spectabilis INA 00606 belonging
      to the phenetic cluster 'S. fulvissimus' were investigated by chemical and NMR
      spectroscopic methods. A teichoic acid from the cell wall of S. spectabilis INA
      00606 was studied in more detail, and this was shown to represent 1,3
      poly(glycerol phosphate) substituted with glucosamine (alpha-D-GlcNAc) and L
      glutamic acid (non-stoichiometric substitution). For the first time, glutamic
      acid is identified as an acyl substituent in teichoic acids of streptomycetes.
      The polymer chain is built of the following fragments: Cell walls of other
      streptomycetes of the phenocluster under study contain 1,3-poly(glycerol
      phosphates) with glucosamine as a glycosyl substituent at O-2 of the glycerol
      phosphate units and L-glutamic acid and lysine as O-2 acyl substituents. Not all
      amino sugar residues in the polymers of these strains are N-acetylated, and the
      content of the glucosamine and lysine residues in the polymers of different
      strains is not the same. Despite certain quantitative differences in the
      structures of the polymers, one may consider streptomycetes of the phenocluster
      'S. fulvissimus' as closely related microorganisms, the details of the structures
      serving as additional criteria for the determination of the species status of a
      strain under study.

PMID- 16458864
TI  - Differential gene expression in central nervous system tissues of sheep with
      natural scrapie.
AB  - The expression of nine genes was analyzed by real-time RT-PCR in the central
      nervous system in order to investigate the molecular pathogenesis of natural
      scrapie. An up-regulation of genes related to glial activation (GFAP) and
      apoptosis (CASP3) was detected in obex and cerebrum, indicating a reactive glia.
      Another glial activation-related gene (CTSS) was slightly up-regulated in obex,
      whereas constitutive expression was detected for SOD1, YWHAZ, PRNP, and the
      apoptosis-related genes BCL2, MCL1, and BAX. This differential gene expression
      might reflect a spatial-temporal and tissue-specific molecular pathogenesis of
      scrapie.

PMID- 16458866
TI  - Lactones of disialyl lactose: characterisation by NMR and mass spectra.
AB  - The lactonisation of alpha-Neup5Ac-(2-->8)-alpha-Neup5Ac-(2-->3)-beta-D-Galp-(1-
      >4)-D-Glc (disialyl lactose) was investigated. (1)H and (13)C NMR chemical shifts
      of disialyl lactose and alpha-Neup5Ac-(2-->8, 1-->9)-alpha-Neup5Ac-(2-->3, 1-->2)
      beta-D-Galp-(1-->4)-D-Glc (disialyl lactose-dilactone) were assigned based on 1D
      and 2D NMR results, including edited HSQC, HSQC-TOSCY and HMBC. The time course
      of lactonisation was followed by thin layer chromatography (TLC) and high
      performance liquid chromatography (HPLC) with electrospray ionisation (ESI) mass
      spectrometry (MS) detection. The rate of lactonisation between alpha-(8)Neu5Ac
      and alpha-(3)Neu5Ac residues (lactonisation at the alpha-(2-->8) linkage) was
      faster than that of lactonisation between alpha-(3)Neu5Ac and Gal residues
      (lactonisation at the alpha-(2-->3) linkage). The mass spectra of disialyl
      lactose, its lactones, alpha-Neup5Ac-(2-->8)-alpha-Neup5Ac (alpha-(2-->8)
      disialic acid) and alpha-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-D-Glc-lactone (3'
      sialyllactose-lactone) showed that the alpha-(2-->8) linkage between Neu5Ac
      residues is difficult to cleave in the ESI-MS, compared with the alpha-(2-->3)
      linkage between Neu5Ac and Gal residues.

PMID- 16458867
TI  - A beta-D-glucan isolated from the fruiting bodies of Hericium erinaceus and its
      aqueous conformation.
AB  - HEP3, a beta-D-glucan slightly soluble in water, was isolated from the alkaline
      extract of the fruiting bodies of Hericium erinaceus. Its chemical structure was
      investigated by methylation analysis, periodate oxidation, Smith degradation and
      by IR and NMR spectroscopy. It was shown to have a main chain composed of beta-(1
      ->3)-linked D-glucopyranosyl residues, with single unit glucosyl branches
      attached to O-6 of every third backbone residue. Viscometry and Congo red
      reaction indicated that HEP3 has a highly ordered hydrogen-bond dependent
      conformation in aqueous solution, which collapses in strong alkaline solution.

PMID- 16458868
TI  - Prostanoid signal transduction and gene expression in the endothelium: role in
      cardiovascular diseases.
AB  - Endothelial cells play an active role in the maintenance of homeostasis.
      Endothelial injury can give rise to endothelial dysfunction in which the profile
      of mediators released by endothelial cells is altered. Among these mediators are
      factors that participate in the development of many cardiovascular disorders.
      Some of the most important are the prostanoids, which can modulate the
      progression of atherosclerosis, arterial hypertension, and angiogenesis.
      Prostanoids are produced by the sequential actions of cyclooxygenases and
      specific synthases and exert their actions through diverse cell-surface and
      nuclear receptors. The profile of prostanoids produced depends on cell type and
      the changing pathophysiological status, and these factors similarly affect the
      great array of biological responses elicited by these molecules. The resulting
      complexity enables extremely subtle and highly complex responses, and this
      provides opportunities for the development of targeted therapeutic approaches.

PMID- 16458869
TI  - Dual isotype expressing B cells [kappa(+)/lambda(+)] arise during the ontogeny of
      B cells in the bone marrow of normal nontransgenic mice.
AB  - Central to the clonal selection theory is the tenet that a single B cell
      expresses a single receptor with a single specificity. Previously, based on our
      work in anti-phosphocholine transgenic mouse models, we suggested that B cells
      escaped clonal deletion by coexpression of more than one receptor on their cell
      surface. We argued that "receptor dilution" was necessary when: (i) the expressed
      immunoglobulin receptor is essential for immune protection against pathogens and
      (ii) this protective receptor is autoreactive and would be clonally deleted,
      leaving a hole in the B cell repertoire. Here, we demonstrate that dual isotype
      expressing B cells arise during the normal ontogeny of B cells in the bone marrow
      and populate both the spleen and peritoneal cavity of nontransgenic mice.
      Furthermore, single cell analysis of the expressed immunoglobulin light chains
      suggests that receptor editing may play a role in the generation of a significant
      fraction of dual isotype expressing B cells.

PMID- 16458870
TI  - Inhibitory effect of luteolin on hepatocyte growth factor/scatter factor-induced
      HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways.
AB  - Hepatocyte growth factor (HGF), also known as scatter factor (SF), and its
      receptor, the c-Met tyrosine kinase, play roles in cancer invasion and metastasis
      in a wide variety of tumor cells. Clinical observations suggest that HGF can
      promote metastasis of hepatoma cells while stimulating tumor invasiveness. We use
      HGF as an invasive inducer of human hepatoma HepG2 cells to investigate the
      effect of flavonoids on anti-invasion. In our preliminary study, we investigated
      the effect of flavonoids including luteolin, quercetin, baicalein, genistein,
      taxifolin and catechin on HGF-mediated migration and invasion of HepG2 cells. We
      found that luteolin presented the most potent potential on anti-migration and
      anti-invasion by Boyden chamber assay. Furthermore, luteolin inhibited HGF
      induced cell scattering and cytoskeleton change such as filopodia and
      lamellipodia was determined by both phase-contrast and fluorescence microscopy
      studies. In addition, Western blotting and immunoprecipitation were performed to
      confirm luteolin suppressed the phosphorylation of c-Met, the membrane receptor
      of HGF, as well as ERK1/2 and Akt, but not JNK1/2, which is activated by HGF. Our
      investigation demonstrated that luteolin similar to PD98059, which acts as a
      specific inhibitor of MEK, an up stream kinase regulating ERK1/2, and wortmannin,
      a PI3K inhibitor, inhibited the invasiveness induced by HGF. In conclusion, the
      luteolin inhibited HGF-induced HepG2 cell invasion involving both MAPK/ERKs and
      PI3K-Akt pathways.

PMID- 16458871
TI  - Structure-activity relationships in the induction of Phase II enzymes by
      derivatives of 3H-1,2-dithiole-3-thione in rats.
AB  - Derivatives of 3H-1,2-dithiole-3-thione (D3T) decrease the incidence and
      multiplicity of tumours in animals exposed to chemical carcinogens by a mechanism
      that is believed to involve their ability to increase tissue activities of Phase
      II detoxification enzymes. One D3T derivative, 4-methyl-5-pyrazinyl-3H-1,2
      dithiole-3-thione (oltipraz) has been investigated as a chemopreventative agent
      in humans, although large-scale trials of this substance were abandoned because
      of toxicity problems. While detailed information on the inductive ability of
      oltipraz is available, little is known of the relative activity of other D3T
      derivatives in vivo. In the present study, the effects of 10 dithiolethiones on
      the activities of two Phase II enzymes, NAD(P)H:quinone acceptor oxidoreductase
      and glutathione S-transferase, have been determined in a number of rat tissues.
      In all tissues, oltipraz was a relatively weak inducer. D3T itself and 5-methyl-,
      4-chloro-5-methyl-, 4-phenyl- and 5,6-dihydrocyclopenta[c]-1,2-dithiole-3-thione
      (cyclopenta) were the most active compounds, both in terms of degree of induction
      and the number of organs in which enzyme induction occurred. Cyclopenta was a
      potent enzyme inducer in the urinary bladder, whereas 4-chloro-5-methyl-3H-1,2
      dithiole-3-thione was particularly effective in the liver and the 4-phenyl
      derivative showed high inductive activity in the lungs. Comparison of the inducer
      activities of selected dithiolethiones, including cyclopenta, in cultured bladder
      carcinoma cells in vitro showed strong correlation with the in vivo data,
      suggesting that the different inducer activity of the dithiolethiones in vivo, at
      least in the bladder, is an intrinsic property of these compounds. In view of the
      evidence that Phase II enzyme induction plays a major role in the chemoprotective
      action of dithiolethiones, evaluation of the anti-cancer activity of the more
      potent inducers identified in this study would be of interest.

PMID- 16458872
TI  - Chondroitin 6-sulfate and dextran sulfate promote hypochlorite-induced
      peroxidation of phosphatidylcholine liposomes.
AB  - In this work, we studied whether chondroitin sulfates and dextran sulfates (DXSs)
      can influence hypochlorite-induced peroxidation of phosphatidylcholine (PC)
      liposomes. Multilamellar liposomes (2 mg lipid/ml) were prepared in phosphate
      buffer, pH 7.4, with NaCl or not and exposed to reagent HOCl/ClO- (1mM) at 37
      degrees C in the presence of different concentrations of chondroitin 6-sulfate
      (C6S), chondroitin 4-sulfate (C4S), DXS 8000, DXS 40,000, and DXS 500,000. Lipid
      peroxidation was assessed by thiobarbituric acid-reactive substance (TBARS)
      production. DXSs and C6S enhanced TBARS production in a dose-dependent manner.
      The decline in TBARS production at the relatively high C6S concentrations may be
      attributed to C4S present in C6S, since in contrast to C6S, C4S is known to react
      with hypochlorite. Dextrans, nonsulfated analogues of DXS, failed to modulate
      TBARS production. This fact indicates the important role of negatively charged
      sulfate groups for DXS to facilitate hypochlorite-induced peroxidation of PC
      liposomes. The electrostatic nature of the mechanism providing for the pro
      oxidative effect of DXS was also supported by the influence of liposome surface
      charge and solution ionic strength on the extent of liposome peroxidation. The
      addition of calcium ions to the incubation mixture did not prevent the pro
      oxidative action of DXS. The relevance of the results to atherogenesis is
      discussed.

PMID- 16458873
TI  - Biological variation at long-term renal post-transplantation.
AB  - In laboratory testing the reference change value (RCV) is used to detect changes
      in a patient's clinical status, even before clinical signs are evident. In a
      previous study we determined the biological variation (BV) of a number of
      constituents during early post-transplantation in kidney recipients to calculate
      useful RCVs for this purpose. RCVs for creatinine and urate were identified as
      the most suitable and were different from those calculated from the normal
      population. The aim of the current study was to determine the BV components at
      long-term following renal transplantation to predict potential crises in
      transplant recipients who have been stable for a number of years. BV components
      for creatinine and urate were calculated in a new group of 40 kidney transplanted
      patients (26 men and 14 women, 29-71 years old) who had been stable for period of
      4 to 7 years following transplantation (long-term post-TR group). An average of 8
      samples per patient was obtained during a period of 1-2 years. Results were
      compared with those from our described group of recently transplanted patients
      (short-term post-TR group). There were no statistically significant differences
      between the groups with regard to within-subject variation or within-subject plus
      analytical variation (CVI+A) for any of the constituents studied. Distribution of
      CVI+A values in long-term post-TR was comparable to that of short-term post-TR
      values. Independence between creatinine and urate was maintained at long-term.
      The fact that BV components for creatinine and urate were similar in short- and
      long-term post-TR and that independence was maintained implies that the short
      term post-TR RCV can also be applied in long-term post-TR patients. The RCV for
      predicting crises in this population represents an optimization of laboratory
      reporting and could be a valuable tool for clinical decision making.

PMID- 16458874
TI  - Detection of Toxoplasma gondii from amniotic fluid, a comparison of four
      different molecular biological methods.
AB  - BACKGROUND: The infection caused by the parasite Toxoplasma gondii (T. gondii) is
      often asymptomatic or has mild symptoms. The infection can cause serious problems
      in pregnant women who acquire the infection during gestation and their fetuses
      are congenitally infected. METHODS: We tested 64 amniotic fluid samples for the
      presence of T. gondii by using fluorescent PCR and DNA fragment analysis. Later
      we compared four different molecular biological methods for the detection of the
      presence of T. gondii on same frozen DNA samples. These methods are the
      conventional PCR, fluorescent PCR with DNA fragment analysis, quantitative real
      time PCR with SYBRGreen I and with fluorescence energy transfer hybridization
      probe detection. We determined the detection limit of these methods. RESULTS: The
      conventional PCR and quantitative real-time PCR with SYBRGreen I detection have
      the detection limit of 1000 parasites, followed by fluorescent PCR with the
      detection limit of 10-100 parasites. The real-time PCR using fluorescence energy
      transfer hybridization probes can detect one parasite. This is the most sensitive
      and the fastest method. We detected 5 T. gondii positive samples with all methods
      from the studied 64 amniotic fluids. CONCLUSIONS: All studied molecular
      biological methods are suitable for the detection of congenital toxoplasmosis.
      The quantitative real-time PCR based methods are more sensitive, simple and easy
      to perform these are opening the avenue to find out the effect of the number of
      parasites on fetal abnormalities.

PMID- 16458875
TI  - Factors determining types and morphologies of calcium oxalate crystals: molar
      concentrations, buffering, pH, stirring and temperature.
AB  - BACKGROUND: Calcium oxalate (CaOx) can be crystallized in several forms and
      morphologies. We evaluated factors that determine differential types and shapes
      of CaOx crystals generated in vitro. METHODS: CaCl2 and Na2C2O4 solutions at
      various molar concentrations were mixed in different conditions (with or without
      Tris-HCl buffer and varying pH, temperature and speed of stirring) and incubated
      overnight. RESULTS: A total of 78 conditions were evaluated. The most frequently
      observed type of CaOx crystals was calcium oxalate monohydrate (COM). In 18.2
      MOmega.cm water, typical monoclinic prismatic form of COM was found when 0.5-1
      mmol/l CaCl2 and 0.5-1 mmol/l Na2C2O4 were mixed, whereas the COM dendrites were
      found when higher concentrations were used. Calcium oxalate dihydrate (COD)
      crystals were observed when 5 mmol/l CaCl2 and 0.5 mmol/l Na2C2O4 were employed.
      With the same molar concentrations of CaCl2 and Na2C2O4, the sequence of adding
      these 2 chemicals into the chamber had some effects on crystal types and
      morphologies. The presence of Tris-HCl buffer in the solution enhanced COM
      crystal growth and aggregation. The pH greater than 5.0 was associated with the
      presence of weddellite COD. Magnetic stirring of the supersaturated solution
      resulted to reduction in size of all crystal forms; the higher speed provided the
      smaller crystals. Finally, crystallization of CaOx at 4 degrees C was more
      efficient than performing the experiment at 25 and 37 degrees C. CONCLUSIONS:
      Molar concentrations, order of adding the substrates, buffering, pH, stirring and
      temperature have significant effects on CaOx crystal formation, types and
      morphologies. Cataloging these differential forms of crystals generated in
      different conditions will be useful for further study on modulations of CaOx
      crystals and kidney stone disease.

PMID- 16458876
TI  - High redox thioredoxin but low thioredoxin reductase activities in the serum of
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Thioredoxin (Trx)/thioredoxin reductase (TrxR) is a redox-active
      system induced by oxidative stress. We investigated its status as a function of
      RA disease activity. METHODS: 64 consecutive RA patients and 27 healthy subjects
      were enrolled in the study. Serum Trx protein levels were evaluated using an
      immunoassay and immunoblot, while redox Trx and TrxR activities and oxidative
      stress markers (carbonyl groups, thiols), were determined using
      spectrophotometric methods. RESULTS: Redox Trx activity and Trx protein
      concentrations were significantly higher in RA patients than in controls (redox
      Trx activity: 37.7+/-22.6 versus 21.1+/-7.9 ng/mL, p<0.01; Trx protein: 25.5+/
      12.0 versus 12.3+/-5.1 ng/mL, p<0.0001). Redox Trx activity correlated with the
      DAS score (r=0.45, p=0.004) and with the tender joint count (r=0.49, p=0.002)
      whereas there was no correlation with Trx protein concentrations. Immunoblot
      analysis showed that circulating Trx was partially aggregated. TrxR activity was
      lower in the serum of RA patients than in healthy subjects (197+/-70 versus 263+/
      56 U/L, p=0.002). TrxR activity was correlated with the DAS score (r=0.53,
      p<0.001) and with the tender joint count (r=0.36, p<0.01). There were no
      correlations between oxidative stress marker levels and redox Trx activity, Trx
      protein concentrations or TrxR activity. CONCLUSION: Redox Trx and TrxR
      activities correlated with the disease activity of RA patients consistent with
      the hypothesis that Trx/TrxR activities may contribute to disease activity in RA.

PMID- 16458877
TI  - Smooth muscle cell injury after cryopreservation of human thoracic aortas.
AB  - The cryopreservation protocol we use for arterial reconstructive surgery has been
      studied to evaluate smooth muscle cell (SMC) structural integrity and viability
      before implantation. Samples of human thoracic aortas (HTA) were harvested from
      five multi-organ donors. Sampling included unfrozen and cryopreserved specimens.
      Cryopreservation was performed using RPMI with human albumin and 10% Me(2)SO in a
      controlled-rate freezing apparatus. Thawing was accomplished by submerging bags
      in a water bath (39 degrees C) followed by washings in cooled saline. In situ
      cell preservation as investigated by light and transmission electron microscopy
      showed that SMCs from cryopreserved HTA had nuclear and cytoplasmic changes. A
      TUNEL assay, performed to detect DNA fragmentation in situ, showed increased SMC
      nuclear positivity in cryopreserved HTA when compared to unfrozen samples. 7-AAD
      flow cytometry assay of cells derived from cryopreserved HTA showed that an
      average of 49+/-16% cells were unlabeled after cryopreservation. Organ cultures
      aimed to study cell ability to recover cryopreservation damage showed a
      decreasing number of SMCs from day 4 to day 15 in cryopreserved HTA. In
      conclusion, the cryopreservation protocol applied in this study induces
      irreversible damage of a significant fraction of arterial SMCs.

PMID- 16458878
TI  - RhoA regulates initiation of invagination, but not convergent extension, during
      sea urchin gastrulation.
AB  - During gastrulation, the archenteron is formed using cell shape changes, cell
      rearrangements, filopodial extensions, and convergent extension movements to
      elongate and shape the nascent gut tube. How these events are coordinated remains
      unknown, although much has been learned from careful morphological examinations
      and molecular perturbations. This study reports that RhoA is necessary to trigger
      archenteron invagination in the sea urchin embryo. Inhibition of RhoA results in
      a failure to initiate invagination movements, while constitutively active RhoA
      induces precocious invagination of the archenteron, complete with the actin
      rearrangements and extracellular matrix secretions that normally accompany the
      onset of invagination. Although RhoA activity has been reported to control
      convergent extension movements in vertebrate embryos, experiments herein show
      that RhoA activity does not regulate convergent extension movements during sea
      urchin gastrulation. Instead, the results support the hypothesis that RhoA serves
      as a trigger to initiate invagination, and once initiation occurs, RhoA activity
      is no longer involved in subsequent gastrulation movements.

PMID- 16458880
TI  - Asymmetrization of first cleavage by transient disassembly of one spindle pole
      aster in the leech Helobdella robusta.
AB  - Unequal first cleavage is characteristic of a diverse group of protostome
      animals. In the nematode Caenorhabditis elegans, unequal first cleavage is
      achieved through the interaction of an apparently symmetric mitotic spindle
      apparatus with a clearly polarized cell cortex. In the clitellate annelid Tubifex
      tubifex, by contrast, the spindle is monastral and contains only one gamma
      tubulin-reactive centrosome; this monastral spindle is inherently asymmetric
      throughout mitosis. Here, we have used immunostaining for beta- and gamma-tubulin
      to follow spindle dynamics during the unequal first cleavage in another
      clitellate annelid, the leech Helobdella robusta. We find that the mitotic
      spindle is diastral and symmetric through early metaphase, then becomes
      asymmetric following the transient down-regulation of one centrosome, as judged
      by gamma-tubulin immunofluorescence. Low levels of drugs that affect microtubule
      dynamics can symmetrize the first cleavage without affecting the gamma-tubulin
      dynamics. Our results provide a striking example of the evolvability of cellular
      mechanisms underlying an unambiguously homologous developmental process.

PMID- 16458879
TI  - Eya1 is required for lineage-specific differentiation, but not for cell survival
      in the zebrafish adenohypophysis.
AB  - The homeodomain transcription factor Six1 and its modulator, the protein
      phosphatase Eya1, cooperate to promote cell differentiation and survival during
      mouse organ development. Here, we studied the effects caused by loss of eya1 and
      six1 function on pituitary development in zebrafish. eya1 and six1 are co
      expressed in all adenohypophyseal cells. Nevertheless, eya1 (aal, dog) mutants
      show lineage-specific defects, defining corticotropes, melanotropes, and
      gonadotropes as an Eya1-dependent lineage, which is complementary to the Pit1
      lineage. Furthermore, eya1 is required for maintenance of pit1 expression,
      leading to subsequent loss of cognate hormone gene expression in thyrotropes and
      somatotropes of mutant embryos, whereas prolactin expression in lactotropes
      persists. In contrast to other organs, adenohypophyseal cells of eya1 mutants do
      not become apoptotic, and the adenohypophysis remains at rather normal size.
      Also, cells do not trans-differentiate, as in the case of pit1 mutants, but
      display morphological features characteristic for nonsecretory cells. Some of the
      adenohypophyseal defects of eya1 mutants are moderately enhanced in combination
      with antisense-mediated loss of Six1 function, which per se does not affect
      pituitary cell differentiation. In conclusion, this is the first report of an
      essential role of Eya1 during pituitary development in vertebrates. Eya1 is
      required for lineage-specific differentiation of adenohypophyseal cells, but not
      for their survival, thereby uncoupling the differentiation-promoting and anti
      apoptotic effects of Eya proteins seen in other tissues.

PMID- 16458881
TI  - Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus
      laevis tadpoles.
AB  - Thyroid hormone (TH) controlled gene expression profiles have been studied in the
      tail, hind limb and brain tissues during TH-induced and spontaneous Xenopus
      laevis metamorphosis. Amplified cRNA probes mixed with a universal standard were
      hybridized to a set of 21,807-sense strand 60-mer oligonucleotides on each slide
      representing the entries in X. laevis UniGene Build 48. Most of the up-regulated
      genes in hind limb and brain are the same. This reflects in part the fact that
      the initial response to TH induction in both tissues is cell proliferation. A
      large number of up-regulated genes in the limb and brain programs encode common
      components of the cell cycle, DNA and RNA metabolism, transcription and
      translation. Notch is one of the few genes that is differentially expressed
      exclusively in the brain in the first 48 h of TH induction studied in these
      experiments. The TH-induced gene expression changes in the tail are different
      from the limb and brain programs. Distinct muscle and fibroblast programs were
      identified in the tail. Dying muscle fibers in tail (marked by active caspase-3)
      up-regulate a group of genes that include proteolytic enzymes. At the climax of
      metamorphosis, tail muscle down-regulates more than half of the genes that encode
      the glycolytic enzymes in the cytoplasm and the tricarboxylic acid pathway and
      all five complexes of the electron transport system in mitochondria. These
      changes in gene expression precede the activation of caspase-3. Some of these
      same energy metabolism-related genes are up-regulated in the limb and brain
      programs by TH. A prominent feature of the tail fibroblasts is the down
      regulation of several collagen and other extra cellular matrix genes and the up
      regulation of hydrolytic enzymes that are responsible for dissolving the
      notochord and resorbing the tail.

PMID- 16458882
TI  - BMP-signaling regulates the generation of hair-cells.
AB  - Bone morphogenetic proteins (BMPs) are diffusible molecules involved in a variety
      of cellular interactions during development. Bmp4 expression accompanies the
      development of the ear sensory organs during patterning and specification of
      sensory cell fates, yet there is no understanding of the role of BMP4 in this
      process. The present work was aimed at exploring the effects of BMP-signaling on
      the development of hair-cells. For this purpose, we studied gene expression, cell
      proliferation and cell death in isolated chick otic vesicles that were grown in
      vitro in the presence of recombinant BMP4 or the BMP-inhibitor Noggin. Cath1 was
      used as a marker for hair-cell specification. BMP4 reduced the number of Cath1
      cells and, conversely, Noggin increased the size of the sensory patches and the
      number of Cath1-positive cells. The effect of BMP4 was irreversible and occurred
      before hair-cell specification. Lfng and Fgf10 were expressed in the prosensory
      domain before Cath1, and their expression was expanded by Noggin. At these
      stages, modifications of BMP activity did not respecify non-sensory epithelium of
      the otic vesicle. The expression of Bmp4 at sensory patches was suppressed by
      BMP4 and induced by Noggin suggesting an autoregulatory loop. Analysis of BrdU
      incorporation during 6 and 18 h indicated that the effects of BMP4 were due to
      its ability to reduce the number of actively proliferating progenitors and
      inhibit cell fate specification. BMP4 induced cell death within the prosensory
      domain of the otic vesicle, along with the expression of Msx1, but not Msx2. On
      the contrary, BMP-inhibition with Noggin favored hair-cell specification without
      changes in the overall cell proliferation. We propose that about the stage of
      terminal division, the balance between BMP and BMP-inhibitory signals regulates
      survival and specification of hair-cell precursors, the final number of sensory
      hair-cells being limited by excess levels of BMPs. The final size of sensory
      patches would hence depend on the balance between BMP4 and opposing signals.

PMID- 16458883
TI  - Long-range upstream and downstream enhancers control distinct subsets of the
      complex spatiotemporal Sox9 expression pattern.
AB  - SOX9 is an evolutionary conserved transcription factor that is expressed in a
      variety of tissues, with essential functions in cartilage, testis, heart, glial
      cell, inner ear and neural crest development. By comparing human and pufferfish
      genomic sequences, we previously identified eight highly conserved sequence
      elements between 290 kb 5' and 450 kb 3' to human SOX9. In this study, we assayed
      the regulatory potential of elements E1 to E7 in transgenic mice using a lacZ
      reporter gene driven by a 529 bp minimal mouse Sox9 promoter. We found that three
      of these elements and the Sox9 promoter control distinct subsets of the tissue
      specific expression pattern of Sox9. E3, located 251 kb 5' to SOX9, directs lacZ
      expression to cranial neural crest cells and to the inner ear. E1 is located 28
      kb 5' to SOX9 and controls expression in the node, notochord, gut, bronchial
      epithelium and pancreas. Transgene expression in the neuroectoderm is mediated by
      E7, located 95 kb 3' to SOX9, which regulates expression in the telencephalon and
      midbrain, and by the Sox9 minimal promoter which controls expression in the
      ventral spinal cord and hindbrain. We show that E3-directed reporter gene
      expression in neural crest cells of the first but not of the second and third
      pharyngeal arch is dependent on beta-catenin, revealing a complex regulation of
      Sox9 in cranial neural crest cells. Moreover, we identify and discuss highly
      conserved transcription factor binding sites within enhancer E3 that are in good
      agreement with current models for neural crest and inner ear development.
      Finally, we identify enhancer E1 as a cis-regulatory element conserved between
      vertebrates and invertebrates, indicating that some cis-regulatory sequences that
      control developmental genes in vertebrates might be phylogenetically ancient.

PMID- 16458884
TI  - Exposure to persistent organic pollutants and hypertensive disease.
AB  - Previous research suggests that exposure to persistent organic pollutants (POPs)
      increases the risk of chronic diseases such as hypertension. We identified the
      zip codes of more than 800 waste sites contaminated with POPs and other
      pollutants, based on which we classified zip codes of upstate New York into three
      groups: "POPs sites", zip codes containing hazardous waste sites with POPs;
      "other waste sites", zip codes containing hazardous waste sites but not with
      POPs; and "clean sites", zip codes without any known hazardous waste sites. Age,
      gender, race, and zip code of residence of patients diagnosed with hypertension
      (ICD-9 codes 401-404) were identified using the New York Statewide Planning and
      Research Cooperative System (SPARCS) for the years 1993-2000. A generalized
      linear model, the negative binomial model, was used to assess the effect of
      living in a zip code with a hazardous waste site on the discharge rate of
      hypertension. After control for the aforementioned covariates, we found a
      statistically significant elevation of 19.2% (95% CI = 8.5%, 31%) in hypertension
      discharge rate for "POPs sites" and a 10% elevation in discharge rates for "other
      waste sites" as compared to "clean sites". In a subset of "POPs sites" where
      people have higher income, smoke less, exercise more and have healthier diets,
      there was still a 13.9% elevation of hypertension discharge rate as compared to
      "clean sites". The results support the hypothesis that living near hazardous
      waste sites, particularly sites containing POPs, may constitute a risk of
      exposure and of developing hypertension.

PMID- 16458885
TI  - Enzymatic studies of cisplatin induced oxidative stress in hepatic tissue of
      rats.
AB  - Cisplatin is an active cytotoxic agent that has proved to be successful in the
      treatment of various types of solid tumors. The drug-induced nephrotoxicity has
      been very well documented in clinical oncology. However, hepatotoxicity has been
      rarely characterized and paid attention to, and is the least studied. We have
      used rat as the model to evaluate the effect of cisplatin on liver antioxidant
      enzymes and to determine whether these modulations in enzymatic activities are
      involved in hepatotoxicity. Reports obtained from our study indicate that
      cisplatin increases lipid peroxidation in the treated tissue of rat. The drug is
      also involved in altering the thiol status of the tissue with concomitant
      alterations in the enzymatic antioxidants. Glutathione and glutathione reductase
      levels were significantly decreased after cisplatin therapy, whereas glutathione
      peroxidase, gamma-glutamyl transpeptidase and catalase showed a significant
      increase. No statistically significant change was observed in glutathione-S
      transferase activity. After cisplatin treatment, cytochrome P 450 showed a
      significant increase, whereas cytochrome b5 was decreased. Thus, an alteration in
      enzymatic antioxidant status with increase in lipid peroxidation indicates that
      the enzymes play an important role in combating free radical induced oxidative
      stress on the tissue.

PMID- 16458886
TI  - Adenosine in the airways: implications and applications.
AB  - Adenosine in a signaling nucleoside eliciting many physiological responses.
      Elevated levels of adenosine have been found in bronchoalveolar lavage, blood and
      exhaled breath condensate of patients with asthma a condition characterized by
      chronic airway inflammation. In addition, inhaled adenosine-5'-monophosphate
      induces bronchoconstriction in asthmatics but not in normal subjects. Studies on
      animals and humans have shown that bronchoconstriction is most likely due to the
      release of inflammatory mediators from mast cells. However a number of evidences
      suggest that adenosine modulates the function of many other cells involved in
      airway inflammation such as neutrophils, eosinophils, lymphocytes and
      macrophages. Although this clear pro-inflammatory role in the airways, adenosine
      may activate also protective mechanisms particularly against lung injury. For
      many years this dual role of adenosine in the respiratory system has represented
      an enigma, and only recently it has become clear that biological functions of
      adenosine are mediated by four distinct subtypes of receptors (A1, A2A, A2B, and
      A3) and that biological responses are determined by the different pattern of
      receptors distribution in specific cells. Therefore, pharmacological modulation
      of adenosine receptors, particularly A2B, may represent a novel therapeutic
      approach for inflammatory diseases. Moreover, as bronchial response to adenosine
      strictly reflects airway inflammation in asthma, bronchial challenge with
      adenosine is considered a valuable clinical tool to monitor airway inflammation,
      to follow the response to anti-inflammatory treatments and to help in the
      diagnostic discrimination between asthma and chronic obstructive lung disease.

PMID- 16458887
TI  - Is ALS a systemic disorder? Evidence from muscle mitochondria.

PMID- 16458888
TI  - Regulation of p90RSK phosphorylation by SARS-CoV infection in Vero E6 cells.
AB  - The 90 kDa ribosomal S6 kinases (p90RSKs) are a family of broadly expressed
      serine/threonine kinases with two kinase domains activated by extracellular
      signal-regulated protein kinase in response to many growth factors. Our recent
      study demonstrated that severe acute respiratory syndrome (SARS)-coronavirus
      (CoV) infection of monkey kidney Vero E6 cells induces phosphorylation and
      dephosphorylation of signaling pathways, resulting in apoptosis. In the present
      study, we investigated the phosphorylation status of p90RSK, which is a well
      known substrate of these signaling pathways, in SARS-CoV-infected cells. Vero E6
      mainly expressed p90RSK1 and showed weak expression of p90RSK2. In the absence of
      viral infection, Ser221 in the N-terminal kinase domain was phosphorylated
      constitutively, whereas both Thr573 in the C-terminal kinase domain and Ser380
      between the two kinase domains were not phosphorylated in confluent cells.
      Ser380, which has been reported to be involved in autophosphorylation by
      activation of the C-terminal kinase domain, was phosphorylated in confluent SARS
      CoV-infected cells, and this phosphorylation was inhibited by , which is an
      inhibitor of p38 mitogen-activated protein kinases (MAPK). Phosphorylation of
      Thr573 was not upregulated in SARS-CoV-infected cells. Thus, in virus-infected
      cells, phosphorylation of Thr573 was not necessary to induce phosphorylation of
      Ser380. On the other hand, Both Thr573 and Ser380 were phosphorylated by
      treatment with epidermal growth factor (EGF) in the absence of p38 MAPK
      activation. Ser220 was constitutively phosphorylated despite infection. These
      results indicated that phosphorylation status of p90RSK by SARS-CoV infection is
      different from that by stimulation of EGF. This is the first detailed report
      regarding regulation of p90RSK phosphorylation by virus infection.

PMID- 16458889
TI  - Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a
      cytochrome P450 with a key role in the biosynthesis of the antimalarial
      sesquiterpene lactone artemisinin.
AB  - Artemisinin, a sesquiterpene lactone endoperoxide derived from the plant
      Artemisia annua, forms the basis of the most important treatments of malaria in
      use today. In an effort to elucidate the biosynthesis of artemisinin, an
      expressed sequence tag approach to identifying the relevant biosynthetic genes
      was undertaken using isolated glandular trichomes as a source of mRNA. A cDNA
      clone encoding a cytochrome P450 designated CYP71AV1 was characterized by
      expression in Saccharomyces cerevisiae and shown to catalyze the oxidation of the
      proposed biosynthetic intermediates amorpha-4,11-diene, artemisinic alcohol and
      artemisinic aldehyde. The identification of the CYP71AV1 gene should allow for
      the engineering of semi-synthetic production of artemisinin in appropriate plant
      or microbial hosts.

PMID- 16458890
TI  - Metabolic engineering to produce phytochromes with phytochromobilin,
      phycocyanobilin, or phycoerythrobilin chromophore in Escherichia coli.
AB  - By co-expression of heme oxygenase and various bilin reductase(s) in a single
      operon in conjunction with apophytochrome using two compatible plasmids, we
      developed a system to produce phytochromes with various chromophores in
      Escherichia coli. Through the selection of different bilin reductases,
      apophytochromes were assembled with phytochromobilin, phycocyanobilin, and
      phycoerythrobilin. The blue-shifted difference spectra of truncated phytochromes
      were observed with a phycocyanobilin chromophore compared to a phytochromobilin
      chromophore. When the phycoerythrobilin biosynthetic enzymes were co-expressed,
      E. coli cells accumulated orange-fluorescent phytochrome. The metabolic
      engineering of bacteria for the production of various bilins for assembly into
      phytochromes will facilitate the molecular analysis of photoreceptors.

PMID- 16458891
TI  - p205, a potential tumor suppressor, inhibits cell proliferation via multiple
      pathways of cell cycle regulation.
AB  - p205 is a member of the interferon-inducible p200 family of proteins that
      regulate cell proliferation. Over-expression of p205 inhibits cell growth,
      although its mechanism of action is currently unknown. Therefore, we evaluated
      the effect of p205 on the p53 and Rb-dependent pathways of cell cycle regulation.
      p205 expression results in elevated levels of p21, and activates the p21 promoter
      in vitro in a p53-dependent manner. In addition, p205 induces increased
      expression of Rb, and binds directly to Rb and p53. Interestingly, p205 also
      induces growth inhibition independent of p53 and Rb by delaying G2/M progression
      in proliferating cells, and is a substrate for Cdk2 kinase activity. Finally, we
      have identified other binding partners of p205 by a yeast two-hybrid screen,
      including the paired homeodomain protein HoxB2. Taken together, our results
      indicate that p205 induces growth arrest by interaction with multiple
      transcription factors that regulate the cell cycle, including but not entirely
      dependent on the Rb- and p53-mediated pathways of growth inhibition.

PMID- 16458892
TI  - GD3-replica peptides selected from a phage peptide library induce a GD3
      ganglioside antibody response.
AB  - GD3-replica peptides were obtained from a phage peptide library and an anti-GD3
      monoclonal antibody (Mab) (4F6), and anti-GD3 Mabs were generated by immunizing a
      peptide GD3P4. A Mab, 3D2 was found to recognize GD3 by immunohistochemical
      approaches. Amino acid analysis of heavy and light chain variable regions of 4F6
      and 3D2 showed that the respective chains had the same length, and only a few
      different amino acid substitutions were found. The present data indicate that the
      immunogenic GD3P4 is processed in a certain size and exposed on the antigen
      presenting cells with a molecular shape quite similar to that of the GD3 epitope
      in 4F6.

PMID- 16458893
TI  - Protection against DNA damage-induced apoptosis by the angiogenic factor
      thymidine phosphorylase.
AB  - Thymidine phosphorylase (TP) is involved both in pyrimidine nucleoside metabolism
      and in angiogenesis. TP also conferred the resistance to hypoxia-induced
      apoptosis of the cancer cells. In U937 cells, DNA damage-inducing agents
      significantly enhanced the expression of TP. Cell lines stably transfected with
      TP cDNA were more resistant to the DNA damage-inducing agents than the mock
      transfected cells and showed augmented activity of Akt. The cytoprotective
      function of TP against DNA damage was independent of its enzymatic activity. The
      resistance to apoptosis was partially abrogated by treatment with the
      phosphatidyl inositol 3-kinase (PI3K) inhibitors, suggesting that the
      cytoprotective function of TP is mediated, at least in part, by regulation of the
      PI3K/Akt pathway. These findings indicate that TP expression in increased by
      various stress including DNA damage and that TP molecules confer resistance to
      DNA damage-induced apoptosis in cancer cells.

PMID- 16458894
TI  - TDP43 depletion rescues aberrant CFTR exon 9 skipping.
AB  - CFTR exon 9 presents a 3' splice site polymorphism, (UG)mU(n), whose composition
      influences splicing. TDP43 specifically binds the UG tract of the transcript and
      inhibits splicing in vitro. We report that depletion of TDP43 through RNA
      interference removes splicing inhibition caused by unfavorable (UG)mU(n)
      sequences, indicating that TDP43 exerts a potent inhibitory effect in vivo. We
      also show that the UG-TDP43 interaction has a dominant role over other exon 9
      splicing regulatory elements. These results suggest that TDP43 association near a
      splice site has determined the evolution of positive splicing regulatory elements
      to contrast this inhibition.

PMID- 16458896
TI  - Ethical considerations and recommendations on oocyte and ovarian
      cryopreservation. FIGO Committee for the Ethical Aspects of Human Reproduction
      and Women's Health.

PMID- 16458895
TI  - Maternal weight gain ranges for optimal fetal growth in Japanese women.
AB  - OBJECTIVE: To identify adequate weight gain ranges during pregnancy in Japanese
      women. METHOD: Obstetric records from 2001 to 2002 for 46,659 term, singleton,
      vaginally delivered live births was used to estimate IUGR and macrosomia risk.
      Total maternal weight gain was grouped according to gestational age-specific
      percentile values of weight gain as follows: "very low" (under the 25th), "low"
      (25th to 49th), "moderate" (50th to 74th), "high" (75th to 89th), and "very high"
      (90th and over). RESULTS: About 6% of infants were identified as having IUGR and
      0.9% as macrosomia. IUGR risk was elevated with low weight gains. Macrosomia risk
      was related to high weight gains and previous spontaneous abortions. CONCLUSION:
      Achieving weight gains between the 50th and 75th percentiles for gestational age
      was considered adequate for optimal fetal growth in Japanese pregnant women.

PMID- 16458897
TI  - Ethical guidelines on conscientious objection. FIGO Committee for the Ethical
      Aspects of Human Reproduction and Women's Health.

PMID- 16458898
TI  - Ethical recommendations on multiple pregnancy and multifetal reduction. FIGO
      Committee for the Ethical Aspects of Human Reproduction and Women's Health.

PMID- 16458899
TI  - Ethical guidelines on sex selection for non-medical purposes. FIGO Committee for
      the Ethical Aspects of Human Reproduction and Women's Health.

PMID- 16458900
TI  - Validity and reliability of a new in vivo ankle stiffness measurement device.
AB  - This investigation was designed to test the validity and reliability of a new
      measure of inversion/eversion ankle stiffness on a unique medial/lateral swaying
      cradle device utilizing a test/retest with comparison to a known standard. Ankle
      stiffness is essential to maintaining joint stability. Most ankle injuries occur
      via an inversion mechanism. To date, very little information is available
      regarding stiffness of the evertor muscles in the prevention of excessive
      inversion joint rotation. Transient oscillation data representing
      inversion/eversion stiffness was obtained in a bipedal weight-bearing stance with
      an upright posture. Using commercially available springs with stiffness of
      4.80N/cm the measured value recorded by the cradle was 4.87N/cm. Mean active
      stiffness values of the ankle were 35.70Nm/cm (SD 9.45). The trial-to-trial
      reliability ICC (2,1) coefficient was 0.96 with an SEM of 2.05Nm/rad, and the day
      to-day reliability ICC (2,k) coefficient was 0.93 and an SEM of 3.00Nm/rad. The
      results demonstrate that inversion/eversion ankle stiffness measures on this
      device are a valid, repeatable and consistent measure. This is relevant because
      the ability to accurately quantify inversion/eversion ankle stiffness will
      improve our understanding of biomechanical stability and factors that influence
      it. It will also enable identification of ankle injury risk factors that will
      lead to more efficient rehabilitation programs and injury prevention strategies.

PMID- 16458901
TI  - Rapid and sensitive determination of pyrethroids indoors using active sampling
      followed by ultrasound-assisted solvent extraction and gas chromatography.
AB  - A fast and simple method to analyze pyrethroids as well as other components of
      frequently used domestic insecticide preparations in indoor air is presented. The
      proposed method, based on sampling with an adsorbent followed by ultrasound
      assisted solvent extraction, was developed with the aim to simplify the
      traditional extraction methodologies applied up to date to determine pesticides
      in air. The analytes were retained on a very small amount of adsorbent, which
      allowed using solely 1 mL of solvent for desorption. The quantification was
      performed by gas chromatography with microelectron-capture detection (GC-muECD)
      and gas chromatography coupled to mass spectrometry (GC-MS). The influence of
      main factors involved in the ultrasound-assisted solvent extraction step (type of
      adsorbent and type of solvent, solvent volume and extraction time) was studied
      using an experimental design approach to account for possible factor
      interactions. The sampling step was studied for two adsorbents (Tenax TA and
      Florisil), finding that 1 m(3) air could be sampled without losses of analytes.
      In this way, the analysis of pyrethroids in air by the proposed method could be
      carried out within a total time shorter than an hour, including sampling.
      Linearity was demonstrated in a wide concentration range. Efficiency of the total
      sampling-extraction process was studied at several concentration levels (2, 10,
      100 and 1000 ng/m(3)), obtaining quantitative recoveries for all compounds, with
      good precision (RSD < 10%). Method detection limits were below 1 ng/m(3) in air
      when GC-muECD was employed, and about one order of magnitude higher for GC-MS. In
      addition, the proposed method was applied to real samples collected in
      contaminated closed rooms, in which some of the target compounds were determined.

PMID- 16458902
TI  - Enantiomeric separation of synthetic 2,3-dihydroxy-3-phenylpropionate compounds
      by beta-cyclodextrin-modified capillary electrophoresis.
AB  - A new capillary electrophoretic method was developed for enantiomeric separation
      and optical impurity analysis of three synthetic 2,3-dihydroxy-3-phenylpropionate
      compounds using native beta-cyclodextrin (beta-CD) as chiral selector and borate
      as a background electrolyte. The separation was carried out in uncoated capillary
      (58.5 cm x 75 microm I.D., effective length 48.5 cm). The results showed that
      beta-CD as the chiral selector exhibited good enantioselectivity and the baseline
      separation was obtained at pH 9.8, 200 mM borate buffer containing 1.7% beta-CD
      at applied voltage 15 kV and capillary temperature 20 degrees C within 15 min.
      The precision of each tested compound was less than 1.0% at migration time and
      5.0% in corrected peak area and the accuracy of the method was in the range of
      98.7-105%. Furthermore, the developed method was successfully applied to the
      determination of the undesirable trace (2S,3R)-(+)-form impurity in the synthetic
      (2R,3S)-(-)-2,3-dihydroxy-3-phenylpropionate samples.

PMID- 16458903
TI  - Pressurized liquid extraction followed by high-performance liquid chromatography
      for determination of seven active compounds in Cortex Dictamni.
AB  - A new method based on pressurized liquid extraction (PLE) followed by a sensitive
      and specific HPLC-DAD analysis is developed for determination of seven compounds
      in Cortex Dictamni. The operational parameters of PLE, such as extraction
      solvent, extraction temperature, extraction pressure, static extraction time,
      flush volume and extraction cycles were optimized, using the extraction
      efficiencies of dictamnine, obacunone and fraxinellone as targets. The optimized
      procedure employed MeOH as extraction solvent, 150 degrees C of extraction
      temperature, 1,500 psi extraction pressure, 5 min of static extraction time, 60%
      flush volume and the extraction recoveries of the three compounds were nearly to
      100% for only one cycle. The following HPLC analysis was performed on a reversed
      phase C(18) column with methanol-water as mobile phase in gradient manner,
      detected at 236 and 218 nm. The limits of detection (LOD) and limits of
      quantification (LOQ) of the seven compounds were in the range of 0.4-15.6 ng and
      1.2-38.8 ng. This assay can be readily utilized as a quality control method for
      Cortex Dictamni and other related medicinal plants.

PMID- 16458904
TI  - Preparation and evaluation of a hydrolytically stable amide-embedded stationary
      phase.
AB  - We have developed a new hydrolytically stable amide-embedded stationary phase via
      a simple and effective synthetic method. The preparation of the new phase
      involves the synthesis of multifunctional silane ligands and the surface
      modification of porous silica particles via multiple attachments of these ligands
      to the silica surface. A hydrolytically stable coating was produced as a result
      of multiple covalent linkages formed between silane ligands and the silica
      surface, and cross-linking between adjacent ligands. The resulting amide-embedded
      stationary phase showed excellent hydrolytic stability over a wide pH range. Like
      other existing amide-embedded columns, this new stationary phase exhibits higher
      retention for polar compounds and different selectivity as compared to
      conventional C18 columns. The new phase is compatible with 100% aqueous mobile
      phases, and also provides high column efficiency and good peak shapes for both
      acidic and basic compounds.

PMID- 16458906
TI  - Rapid analysis of stilbenes and derivatives from downy mildew-infected grapevine
      leaves by liquid chromatography-atmospheric pressure photoionisation mass
      spectrometry.
AB  - Resveratrol, trans-epsilon-viniferin and trans-delta-viniferin are the major
      stilbenes induced in downy mildew infected grapevine leaves. In addition, nine
      minor polyphenolic compounds, described as stilbenes derivatives, have been
      separated and detected among known stilbenes after a methanolic microextraction
      of small pieces (1-2 mg) from infected grapevine leaves with a rapid, qualitative
      and optimized HPLC method coupled to mass spectrometry using atmospheric pressure
      photoionisation (APPI-MS(n)). The characterization of unknown stilbenic
      derivatives as six resveratrol dimers, two dimethylated resveratrol dimers and a
      resveratrol trimer are reported. Therefore, structures have been proposed for the
      dimethylated resveratrol dimers. Use of an easy sample treatment and the LC-APPI
      MS(n) method results in spectral data of these minor naturally occurring
      viniferin analogues.

PMID- 16458905
TI  - Cationic lipid vesicles as coating precursors in capillary electrochromatography:
      separation of basic proteins and neutral steroids.
AB  - 1,2-Dioleyl-3-trymethylammoniumpropane (DOTAP) lipid vesicles were employed as
      coating precursors to obtain a semipermanent cationic lipid bilayer in silica
      capillary. The coating procedure was relatively fast and simple. Reliable results
      for the separation of four basic proteins (alpha-chymotrypsinogen A, ribonuclease
      A, cytochrome C, lysozyme) were obtained by using an acetate buffer under acidic
      conditions. The RSDs of the migration times were not higher than 0.5% run-to-run
      and about 1% day-to-day (3 days), while the RSDs of the peak areas were within 7%
      day-to-day (3 days). The day-to-day RSD of the EOF mobility of about 1%,
      confirmed that the DOTAP coating was stable for the separation of basic proteins,
      under acidic buffers. In addition to basic proteins the DOTAP coating was found
      suitable under acidic conditions for the repeatable separation of neutral
      steroids. The potential of DOTAP as a carrier in background electrolyte solution
      was studied.

PMID- 16458907
TI  - Microchannel-electrode alignment and separation parameters comparison in
      microchip capillary electrophoresis by scanning electrochemical microscopy.
AB  - The end of separation channel in a microchip was electrochemically mapped using
      the feedback imaging mode of scanning electrochemical microscopy (SECM). This
      method provides a convenient way for microchannel-electrode alignment in
      microchip capillary electrophoresis. Influence of electrode-to-channel positions
      on separation parameters in this capillary electrophoresis-electrochemical
      detection (CE-ED) was then investigated. For the trapezoid shaped microchannel,
      detection in the central area resulted in the best apparent separation efficiency
      and peak shape. In the electrode-to-channel distance ranging from 65 to 15mum,
      the limiting peak currents of dopamine increased with the decrease of the
      detection distance due to the limited diffusion and convection of the sample
      band. Results showed that radial position and axial distance of the detection
      electrode to microchannel was important for the improvement of separation
      parameters in CE amperometric detection.

PMID- 16458908
TI  - Simultaneous determination of saponins and fatty acids in Ziziphus jujuba
      (Suanzaoren) by high performance liquid chromatography-evaporative light
      scattering detection and pressurized liquid extraction.
AB  - The seed of Ziziphus jujube Mill. var. spinosa (Bunge) Hu ex H. F. Chou,
      Suanzaoren in Chinese, is one of commonly used Chinese medicines. Saponins and
      fatty oil contains several fatty acids in Suanzaoren are responsible for its
      therapeutic activities. In this study, a new HPLC coupled with evaporative light
      scattering detection (ELSD) and pressurized liquid extraction (PLE) method was
      developed for the simultaneous quantitative determination of 11 major components
      of 2 saponins and 9 fatty acids, namely jujuboside A, jujuboside B, lauric acid,
      myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid,
      linoleic acid, arachidic acid and docosanoic acid in Suanzaoren. Simultaneous
      separation of these eleven compounds was achieved on a C18 analytical column. The
      mobile phase consisted of (A) 0.1% aqueous acetic acid and (B) methanol with 0.1%
      acetic acid using a gradient elution. The drift tube temperature of ELSD was set
      at 75 degrees C, and nitrogen flow-rate was 1.8l/min. All calibration curves
      showed good linearity (r(2)>0.9955) within test ranges. This method showed good
      reproducibility for the quantification of these eleven components in Suanzaoren
      with intra- and inter-day variations of less than 3.41 and 4.37%, respectively.
      The validated method was successfully applied to quantify 11 investigated
      components in nine commercial samples of Suanzaoren.

PMID- 16458909
TI  - Experiments directed to the compound-specific determination of the stable carbon
      isotope ratios of the Toxaphene congener B8-1413 in two technical mixtures and
      Antarctic Weddell seal.
AB  - The carbon stable isotope ratio (delta(13)C value) of an environmentally-relevant
      Toxaphene congener in technical products and a biological sample from a remote
      region was in the focus of this work. For this reason, the major
      octachlorobornane residue of the multicomponent pesticide Toxaphene in biological
      samples, 2-endo,3-exo,5-endo,6-exo,8,8,10,10-octachlorobornane (B8-1413 or P26),
      was quantitatively enriched from two technical Toxaphene mixtures (Toxaphene and
      Melipax) in duplicates as well as from an Antarctic Weddell seal sample. Normal
      phase followed by reversed-phase high-performance liquid chromatography (HPLC)
      with three columns, respectively, coupled in series was used for this purpose.
      Four of the five fractionated samples fulfilled the requirement of an
      interference-free GC-elution for subsequent determination of the delta(13)C value
      by gas chromatography interfaced to an isotope ratio mass spectrometer (GC-IRMS).
      B8-1413 in Toxaphene (n=1) was more depleted in (12)C than in Melipax (n=2),
      which agrees with previous results obtained for the entire mixtures. The B8-1413
      isolate from a Weddell seal sample from the Antarctic showed a delta(13)C value
      between the two technical products. Although a source appointment to the one or
      the other product was not possible, this example indicates that long range
      transport to the Antarctic and by uptake and food-chain bioaccumulation of B8
      1413 in seals did not change the delta(13)C value significantly. The observed
      differences in one duplicate sample indicate that statistic evaluation of samples
      used for isotope ratio MS measurements is an important issue.

PMID- 16458910
TI  - Suppressed anion chromatography using mixed zwitter-ionic and carbonate eluents.
AB  - Effect of mixed eluents which contain zwitterions such as 2-(N
      morpholino)ethanesulfonic acid (MES), 3-(N-morpholino)propanesulfonic acid
      (MOPS), 2-(cyclohexylamino)ethanesulfonic acid (CHES) and 3-(cyclohexylamino)-1
      propanesulfonic acid (CAPS) and carbonate for suppressed conductivity ion
      chromatography (IC) were studied. The retention behaviors of all species were
      affected with different anion exchange columns when adding some zwitterion into
      carbonate eluent. The retention time of all species, especially those of strong
      retetion, was substantially shortened in AS14A column with either Na(2)CO(3)/CHES
      or Na(2)CO(3)/CAPS as eluent while a general increase in retetion time was
      noticed in AS9-HC column. Low pH of eluent was achieved when zwitterion was
      added. Without much changes in the background conductivity after suppressed, CHES
      could be used as suppressed conductivity ion chromatography eluent for
      determination of species unstable in strong alkaline, such as determination of
      phosphate in heteropoly acid (HPA) samples in AS14 column. The mixed eluent could
      also affect the selectivity when it was applied to the study of simultaneous
      separation of anions and cations in AS9-HC column by suppressed ion
      chromatography.

PMID- 16458911
TI  - Surface chemical studies on selective separation of pyrite and galena in the
      presence of bacterial cells and metabolic products of Paenibacillus polymyxa.
AB  - Selective separation of pyrite and galena from mixture of the two minerals was
      achieved through interaction with cells and metabolic products from a culture of
      Paenibacillus polymyxa. Adsorption of cells and metabolic products onto minerals
      and electrokinetic studies of minerals after interaction with cells and metabolic
      products were carried out to examine the resulting surface modification on the
      mineral surfaces. Flocculation and flotation techniques were successfully applied
      in the selective separation of minerals after bacterial interaction. The effect
      of varying conditions for production of extracellular polysaccharides and protein
      provided an insight into the possible mechanism involved in microbially induced
      flocculation and flotation of pyrite and galena.

PMID- 16458912
TI  - In situ sensing of metal ion adsorption to a thiolated surface using surface
      plasmon resonance spectroscopy.
AB  - The kinetics of the adsorption of metal ions onto a thiolated surface and the
      selective and quantitative sensing of metal ions were explored using surface
      plasmon resonance (SPR) spectroscopy. The target metal ion was an aqueous
      solution of Pt2+ and a thin-gold-film-coated glass substrate was modified with
      1,6-hexanedithiol (HDT) as a selective sensing layer. SPR spectroscopy was used
      to examine the kinetics of metal ion adsorption by means of the change in SPR
      angle. The selectivity of the thiolated surface for Pt2+ over other divalent
      metal ions such as Cu2+, Ni2+, and Cd2+ was evident by the time-resolved SPR
      measurement. SPR angle shift, deltatheta(SPR), was found to increase
      logarithmically with increasing concentration of Pt2+ in the range of 1.0 x 10(
      5)-1.0 mM. The rate of Pt2+ adsorption on HDT observed at both 0.1 and 1 mM Pt2+
      accelerates until the surface coverage reaches approximately 17%, after which the
      adsorption profile follows Langmuirian behavior with the surface coverage. The
      experimental data indicated that heavy metal ions were adsorbed to the
      hydrophobic thiolated surface by a cooperative mechanism. A mixed self-assembled
      monolayer (SAM) composed of HDT and 11-mercaptoundecanoic acid was used to reduce
      the hydrophobicity of the thiol-functionalized surface. The addition of
      hydrophilic groups to the surface enhanced the rate of adsorption of Pt2+ onto
      the surface. The findings show that the adsorption of metal ions is strongly
      dependent upon the hydrophilicity/hydrophobicity of the surface and that the
      technique represents an easy method for analyzing the adsorption of metal ions to
      a functionalized surface by combining SPR spectroscopy with a SAM modification.

PMID- 16458913
TI  - Study on the formation and depolymerization of acridine orange dimer in acridine
      orange-sodium dodecyl benzene sulfonate-protein system.
AB  - Experiment indicates that the fluorescence of acridine orange (AO) can be greatly
      quenched by anionic surfactant sodium dodecyl benzene sulfonate (SDBS), but when
      protein is added into the AO-SDBS system, the fluorescence intensity of the
      latter is enhanced. It is considered that SDBS can promote the formation of AO
      dimer, resulting in the quenching of the fluorescence of AO. When bovine serum
      albumin (BSA) is added into AO-SDBS system, BSA and SDBS can interact and form
      negative micelle-like cluster complex with "aromatic ring stacking," which
      destroys the formation conditions of AO dimer and makes some AO dimers turn into
      monomer, resulting in the fluorescence enhancement of AO-SDBS system. Whereas the
      positive AO and residual AO dimer are dissolved in the negative BSA-SDBS cluster
      through electrostatic and hydrophobic forces and form a large association. Here,
      the fluorescence enhancement of AO-SDBS is considered to originate from the
      hydrophobic microenvironment provided by BSA and SDBS, the depolymerization of AO
      dimer and intermolecular energy transfer between BSA and AO.

PMID- 16458914
TI  - Preparation of cerium-loaded Y-zeolites for removal of organic sulfur compounds
      from hydrodesulfurizated gasoline and diesel oil.
AB  - Ce(IV)-loaded Y-zeolites (CeY) were prepared for selective removal of the trace
      amount of organic sulfur compounds from hydrodesulfurization (HDS)-treated diesel
      oil. The CeY samples can be obtained from NH4-Y-zeolite (NH4Y) using liquid-phase
      ion-exchange and solid-state ion-exchange methods. The ion-exchange reactions,
      structures, and selective adsorptions of organic sulfur compounds of the CeY
      samples were investigated using XRD, IR, XPS, TEM, and GC sulfur analyzer. The
      organic sulfur compound uptakes strongly depend on the amount and the valency of
      Ce in the zeolite structure. Ce(IV) shows much higher adsorptive ability than
      Ce(III). A CeY-S sample prepared by solid-state ion-exchange reaction of NH4Y and
      Ce(NO3)3 with Ce/NH4 mole ratio of 0.63 at 250 degrees C showed a maximum sulfur
      uptake from a model solution of HDS-treated gasoline containing thiophene [S = 5
      ppm (ppm = mg/L)]. A desulfurization from a HDS-treated diesel oil containing
      organic sulfur compounds (S = 1.87 ppm) and H2S (S = 0.73 ppm) was investigated
      with a combination of the CeY-S and a CuO adsorbent for removal of H2S by a batch
      method. The sulfur content was reduced to below 0.01 ppm for the first time. This
      method provides a promising desulfurization process to prepare a clean fuel for
      fuel cells.

PMID- 16458915
TI  - Surface enhanced Raman scattering based on silver dendrites substrate.
AB  - A simple method of the reduction of AgNO3 by copper foil in aqueous medium was
      used to prepare silver dendrites, which can be used as a novel good reproducible
      surface enhanced Raman scattering (SERS) active substrate. The SERS spectra of 4
      pyridinethiol on this novel substrate reflected the different SERS activities on
      the minuteness and strong Ag dendrites. The electromagnetic coupling enhancement
      and chemical enhancement mechanisms are used to explain the SERS effect.

PMID- 16458916
TI  - Direct-write fabrication of colloidal photonic crystal microarrays by ink-jet
      printing.
AB  - An array of the colloidal photonic crystals was directly fabricated using an ink
      jet printing. The colloidal ink droplets containing the monodispersed polystyrene
      latex particles were selectively deposited on a hydrophobic surface. Solvent
      evaporation from each ink droplet leads to a formation of microdome-shaped
      colloidal assembles of close-packed structures. Microspectroscopic analysis has
      confirmed that the individual assembly serves as a photonic crystal and its
      optical properties can be correlated with the microstructural features. Unlike
      other techniques of patterned growth of colloidal photonic crystal, the substrate
      does not need to be patterned first and no template is needed in the direct
      writing by the ink-jet printing. Using our strategy, we have rapidly produced the
      colloidal photonic crystal microarrays composed of different-sized spheres
      addressably patterned on the same substrate.

PMID- 16458917
TI  - Competitive sorption and desorption of heavy metals in mine soils: influence of
      mine soil characteristics.
AB  - Many mine soils are chemically, physically, and biologically unstable and
      deficient. They are sometimes amended with sewage sludge and ashes but often
      contain heavy metals that increase the already high mine soils' heavy metal
      contents. Cd, Cr, Cu, Ni, Pb, and Zn in mutual competition were added to five
      mine soils (Galicia, Spain). Soil capacities for heavy metal sorption and
      retention were determined by means of distribution coefficients and selectivity
      sequences among metals. Influence of soil characteristics on sorption and
      retention was also examined. Retention selectivity sequences indicate that, in
      most of the soils, Pb is the preferred retained metal, followed by Cr. The last
      metals in these sequences are Ni, Cd, and Zn. Soil organic matter content plays a
      fundamental role in control of Pb sorption. Gibbsite, goethite, and mica
      influence Cr retention. Soil organic matter, oxides, and chlorite contents are
      correlated with K(d sigma sp medium). Heavy metals are weakly adsorbed by soils
      and then desorbed in high amounts. To recover these soils it is necessary to
      avoid the use of residues or ashes that contain heavy metals due to their low
      heavy metal retention capacity.

PMID- 16458918
TI  - Measurement of high affinity antibodies on antigen-immunoblots.
AB  - We describe a semi-quantitative method for measuring the relative affinity of
      antigen-specific oligoclonal IgG bands separated by isoelectric focusing followed
      by blotting onto antigen-coated membrane and incubation with sodium thiocyanate.
      When the developed blot is digitised in greyscale, densitograms can be made and
      peak areas calculated using ImageJ freeware. By expressing peak area as a
      percentage of the total area under the curve we have shown that there is a
      statistically significant rise in percentage of peak area for a given band which
      persists with increasing molarities of sodium thiocyanate.

PMID- 16458919
TI  - Quantitation of ovine cytokine mRNA by real-time RT-PCR.
AB  - In this study we describe for the first time the dynamics of the expression of
      the cytokines, IL-1beta, IL-12p40, TNFalpha in ovine dendritic cells and
      macrophages after LPS stimulation. Real time RT-PCR was used for the quantitation
      of these cytokines and IL-4 and IFNgamma as well as two potential housekeeping
      genes (HKG), ATPase and GAPDH, in mRNAs from ovine leucocyte populations. Both
      dual-labelled probes (TAMRA/FAM) and SYBR Green assays were utilised, using a
      Corbett Research RotorGene and ABI 7700 machine. In order to quantitate each
      cytokine in our assays all C(T) values were compared to a standard curve
      generated using plasmid DNA containing the cytokine of interest. To validate our
      assays, concanavalin A-stimulated peripheral blood mononuclear cells (PBMCs) and
      LPS-stimulated monocyte-derived dendritic cells (MoDC) and monocyte-derived
      macrophages (MDMO) were examined. We found that peak cytokine mRNA expression was
      between 3 and 6 h for the cytokines examined except for IL-12p40 where peak
      cytokine release was around 12 h post-stimulation in MDMO and PBMCs. However, in
      MoDCs, peak IL-12p40 mRNA expression was observed within 3-6 h. We have
      identified a sensitive and reliable method for the identification of ovine
      cytokine mRNAs.

PMID- 16458921
TI  - Exploring transcription factor binding properties of several non-coding DNA
      sequence elements in the human NF-IL6 gene.
AB  - We examined several DNA segments upstream of the transcription start site of the
      human NF-IL6 gene to evaluate the predictions of two computational models
      developed to identify potential regulatory elements in the non-coding regions of
      genes. One model, comparative genomics, is based on the hypothesis that
      functional regulatory sequences can be localized in alignments of genomic DNA
      from several species. The other model is based on the hypothesis that protein
      binding sites in genomic DNA may include sequence elements that occur frequently
      in proximal promoters of genes. The segments selected for DNA binding and
      functional evaluations included: (1) two conserved regions identified in multi
      species sequence alignments; (2) a region containing several localized hits with
      9-mers that ranked highly in studies of proximal promoters of human genes; and
      (3) two regions that were either GC-rich and/or contained tracts of G. The assays
      were done under nearly identical experimental conditions, using a cell line
      (U937) representing human monocytes/macrophages. The experiments also aimed at
      evaluating what effect, if any, cellular stimulation could have on the
      interactions of nuclear proteins with naturally occurring GC-rich elements in a
      human genomic DNA. In DNA binding assays, several complexes were formed with the
      conserved regions identified in multi-species sequence alignment. Furthermore,
      these regions were active in functional assays. The region containing several
      matches with 9-mers derived from proximal promoters of human genes was not
      conserved but formed several complexes with nuclear proteins including Sp1, Egr
      1, and an unidentified protein. In addition, this region was active in functional
      assays and responded to cellular stimulations. Overall, the results of the assays
      suggest an important role for the sequence context of genomic DNA in protein
      binding and selection.

PMID- 16458920
TI  - Identification, localization and interaction of SNARE proteins in atrial cardiac
      myocytes.
AB  - Atrial cardiac myocytes secrete the vasoactive hormone atrial natriuretic peptide
      (ANP) by both constitutive and regulated exocytotic fusion of ANP-containing
      large dense core vesicles (LDCV) with the sarcolemma. Detailed information,
      however, regarding the identity and function of specific membrane fusion proteins
      (SNARE proteins) involved in exocytosis in the endocrine heart is lacking. In the
      current study, we identified SNARE proteins and determined their association with
      ANP-containing secretory granules using primary cultures of neonatal and adult
      rat atrial cardiac myocytes. Using RT-PCR, cardiac myocytes were screened for
      SNARE and SNARE-associated transcripts. Identified SNARE proteins that have been
      implicated in exocytosis in neuroendocrine cells were further characterized by
      Western blot analysis. Functional interaction between SNARE proteins was
      demonstrated using immunoprecipitation. Using cell fractionation and
      immunocytochemical methods, it was revealed that VAMP-1, VAMP-2 and synaptotagmin
      1 (the putative Ca(2+) sensor) localized to subpopulations of ANP-containing
      secretory granules in atrial myocytes. Currently, there is conflicting data
      regarding the role of Ca(2+) in ANP exocytosis. To judge whether secretory
      activity could be evoked by intracellular Ca(2+) elevation, time-resolved
      membrane capacitance measurements were used in combination with the flash
      photolysis of caged compounds to follow the exocytotic activity of single
      neonatal atrial myocytes. These studies demonstrated that multiple SNARE proteins
      are present in neonatal and adult cardiac myocytes and suggest the importance of
      Ca(2+) in exocytosis of ANP from neonatal atrial cardiac myocytes.

PMID- 16458922
TI  - The surgical management of Graves' disease.
AB  - BACKGROUND: The historical aspects of the pathophysiology and treatment of
      Graves' disease are briefly discussed in this paper. MATERIALS AND METHODS: The
      three treatment modalities of Graves' disease are anti-thyroid drug therapy,
      radioactive iodine therapy, and surgery. Although the majority of patients with
      Graves' disease in the U.S. are treated with radioactive iodine, surgery still
      plays an important role when patients cannot tolerate anti-thyroid drug therapy,
      when medical treatment is rejected by patients, or when surgery is deemed the
      fastest and safest route in managing the patient. CONCLUSIONS: The indications
      for surgical management of Graves' disease are discussed with emphasis on
      available data supporting the extent of thyroid resection based on the incidences
      of hypothyroidism, recurrence of hyperthyroidism, recurrent laryngeal nerve
      injury and hypoparathyroidism.

PMID- 16458923
TI  - Therapeutic potential of chitosan and its derivatives in regenerative medicine.
AB  - BACKGROUND: Cell-based transplantation, tissue engineering and gene therapy are
      important therapeutic strategies for present and future regenerative medicine.
      One challenge is to present the target cells in a suitable matrix to allow the
      cells to survive the wound contraction, tissue repair, and remodeling in certain
      tissues. Recently, functional biomaterial research has been directed towards the
      development of improved scaffolds and new drug delivery systems for regenerative
      medicine. MATERIALS AND METHODS: A literature survey was performed in basic and
      clinic publications relevant to the therapeutic potential of chitosan and its
      derivatives in regenerative medicine. In this review the functional properties
      and potential applications of chitosan and its derivatives in regenerative
      medicine are presented and discussed. RESULTS: Chitosan can be obtained by
      alkaline deacetylation of chitin and is found to be a natural-based nontoxic,
      biocompatible, and biodegradable polymer with anti-microbial activity. Chitosan
      and its derivatives could accelerate wound healing by enhancing the functions of
      inflammatory cells and repairing cells. Recent studies further indicated that
      chitosan and its derivatives also are novel scaffold materials for tissue
      engineering and are-promising non-viral vectors for gene delivery. CONCLUSIONS:
      Regenerative medicine has entered a new era with the development of modern
      science and technology. The novel properties of chitosan make it a versatile
      biomaterial for cell therapy, tissue engineering and gene therapy. It is hoped
      that these diverse approaches for regenerative medicine will translate from
      "bench to bedside" in the future.

PMID- 16458924
TI  - Matrix metalloproteinase 2 polymorphisms in a caucasian population with abdominal
      aortic aneurysm.
AB  - BACKGROUND: The formation of sporadic abdominal aortic aneurysm (AAA) is
      explained by remodeling of the extracellular matrix (ECM) and breakdown of
      structural components of the vascular wall. Matrix metalloproteinase 2 (MMP2) is
      one of the principal matrix-degrading proteases and is known to play a major role
      in the remodeling of the extracellular matrix in arterial vessels. Increased MMP2
      expression in the extracellular matrix of the walls of AAAs has been shown in
      several studies. To investigate the possible impact of genetic variants of the
      MMP2 gene in the etiology of AAA, we conducted this case-control study. PATIENTS
      AND METHODS: We analyzed MMP2 single-nucleotide polymorphisms (SNPs) in 51
      patients with AAA and 48 controls. Differences in genotype and allele frequencies
      of identified polymorphisms were determined after sequencing the entire coding
      region and three selected parts of the promoter. RESULTS: Eighteen polymorphisms
      were identified, 6 of which are newly described, with 3 located in the introns
      (c.IVS1+31C>G, c.IVS7-18G>A, c.IVS10+26C>T) and 3 located in the coding region
      (c.124G>A, c.1368C>T, c.1860C>T). There were no statistically significant
      differences in genotype or allele frequencies between the two groups.
      CONCLUSIONS: Our analysis of the entire coding region and three parts of the
      promoter of the MMP2 gene failed to show an association between genetic
      polymorphisms and AAA, suggesting that variations in the MMP2 gene do not
      contribute to the development of AAA.

PMID- 16458925
TI  - Prometheus' challenge: molecular, cellular and systemic aspects of liver
      regeneration.
AB  - The fascinating aspect of the liver is the capacity to regenerate after injury or
      resection. A variety of genes, cytokines, growth factors, and cells are involved
      in liver regeneration. The exact mechanism of regeneration and the interaction
      between cells and cytokines are not fully understood. There seems to exist a
      sequence of stages that result in liver regeneration, while at the same time
      inhibitors control the size of the regenerated liver. It has been proven that
      hepatocyte growth factor, transforming growth factor, epidermal growth factor,
      tumor necrosis factor-alpha, interleukins -1 and -6 are the main growth and
      promoter factors secreted after hepatic injury, partial hepatectomy and after a
      sequence of different and complex reactions to activate transcription factors,
      mainly nuclear factor kappaB and signal transduction and activator of
      transcription-3, affects specific genes to promote liver regeneration. Unraveling
      the complex processes of liver regeneration may provide novel strategies in the
      management of patients with end-stage liver disease. In particular, inducing
      liver regeneration should reduce morbidity for the donor and increase faster
      recovery for the liver transplantation recipient.

PMID- 16458926
TI  - Combined enzymatic and antioxidative treatment reduces ischemia-reperfusion
      injury in rabbit skeletal muscle.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury is characterized by the production
      of oxygen-free radicals leading to disturbances in vasomotility (microvascular
      constriction) and microvascular permeability (interstitial edema formation). The
      objective was to evaluate the effect of the combined antioxidative and enzymatic
      preparation Phlogenzym on I/R injury of skeletal muscle. MATERIALS AND METHODS: A
      rabbit hindlimb model of I/R (2.5/2 h) was used (IR group). Phlogenzym,
      containing rutin, trypsin, and bromelain, was applied enterally (60 mg/kg body
      weight) as a bolus 30 min prior to ischemia (Ph group). Sham-operated animals
      served as controls (CO group). Plasma malondialdehyde, potassium, and
      microvascular perfusion (monitored by laser flowmetry) were assessed.
      Histomorphometry and electron microscopy were performed from major adductor
      muscles. RESULTS: Two hours after reperfusion, potassium levels were
      significantly elevated in IR compared to Ph group (6.7 +/- 1.2 versus 4.9 +/- 0.9
      mmol/l, P < 0.006). Enhanced lipid peroxidation, apparent by increased plasma
      malondialdehyde levels, was ameliorated in the Ph group (1.0 +/- 0.1 versus 0.7
      +/- 0.1 nmol/ml, P < 0.0001). No-reflow (reduction of blood flow by 62% in IR
      group) was not observed in the Ph group (P < 0.004). Phlogenzym treatment
      prevented microvascular constriction (17.6 +/- 2.3 versus 12.6 +/- 1.1 microm(2),
      P < 0.0001) and mollified interstitial edema (21.5 +/- 2.0 versus 26.0 +/- 3.7%,
      P < 0.017), resulting in mild ultrastructural alterations in contrast to
      pronounced sarcolemmal and mitochondrial damage in untreated rabbits.
      CONCLUSIONS: Phlogenzym had a protective effect on skeletal muscle during I/R
      injury expressed by prevention of no-reflow and preservation of muscle tissue.

PMID- 16458927
TI  - Combination of pre-operative radiotherapy and surgery suppresses local
      accumulation of collagen and TGF-beta1 in rats.
AB  - BACKGROUND: The systemic and local tissue repair responses of radiation in
      combination with surgery are still unclear. We have studied the effect of
      fractionated pre-operative radiotherapy with or without subsequent laparotomy on
      collagen accumulation using a rodent model. MATERIALS AND METHODS: Thirty-two
      male Sprague-Dawley rats were divided into four groups (eight rats per group): 1)
      sham radiation and sham laparotomy (control); 2) sham radiation and laparotomy;
      3) radiation and sham laparotomy; and 4) radiation followed by laparotomy.
      Expanded polytetrafluoroethylene (ePTFE) tubes were implanted subcutaneously in
      the abdominal wall in the radiotherapy field and on the back outside the
      radiotherapy field day 0. The abdomen (3 cm x 4 cm) was irradiated day 3 (10 Gy)
      and again day 7 (10 Gy). On day 10, implants were extirpated, laparotomy
      undertaken in groups 2 and 4 and new ePTFE tubes implanted subcutaneously. The
      second implants were extirpated on day 20. Implants were analyzed for
      hydroxyproline, total protein and transforming growth factor-beta1 (TGF-beta1)
      levels. RESULTS: On day 10, hydroxyproline (P < 0.05) and TGF-beta1 (P < 0.001)
      were lower in ePTFE tubes in irradiated compared with non-irradiated rats. On day
      20, the abdominal ePTFE hydroxyproline remained low (P < 0.001) in animals
      subjected to laparotomy and pre-operative irradiation while hydroxyproline levels
      of rats subjected to irradiation only were similar to controls. The effects of
      radiation on hydroxyproline were confined to the irradiated abdominal area. There
      was a positive correlation between hydroxyproline and TGF-beta1 levels in the
      abdominal wall implant day 20 (r = 0.53, P < 0.005). CONCLUSION: A clinically
      relevant fractionated radiation scheme reduced subcutaneous collagen accumulation
      pre-operatively and profoundly within the radiation field post-operatively after
      laparotomy, possibly because of lowered TGF-beta1 levels.

PMID- 16458928
TI  - A new missense mutation in caveolin-3 gene causes rippling muscle disease.
AB  - Mutations of the Cav-3 gene are associated with distinct, sometimes overlapping
      muscle disease phenotypes. We report a new Italian family with autosomal dominant
      rippling muscle disease. Immunocytochemical analysis of muscle showed a deficit
      of caveolin-3 protein and molecular genetic analysis showed a novel mutation of
      the Cav-3 gene.

PMID- 16458929
TI  - The species-area relationship and evolution.
AB  - Models relating to the species-area curve usually assume the existence of
      species, and are concerned mainly with ecological timescales. We examine an
      individual-based model of co-evolution on a spatial lattice based on the tangled
      nature model in which species are emergent structures, and show that
      reproduction, mutation and dispersion by diffusion, with interaction via genotype
      space, produces power-law species-area relations as observed in ecological
      measurements at medium scales. We find that long-lasting co-evolutionary habitats
      form, allowing high diversity levels in a spatially homogenous system.

PMID- 16458930
TI  - Characterisation of CGRP receptors in the human isolated middle meningeal artery.
AB  - Although the understanding of migraine pathophysiology is still incomplete, there
      seems to be little doubt that dilatation of cranial blood vessels, including
      meningeal arteries, is involved in the headache phase of migraine. Since
      calcitonin gene-related peptide (CGRP) has been implicated in this
      vasodilatation, the present study set out to compare the relaxant effects of the
      endogenous ligand h-alphaCGRP, and [ethylamide-Cys(2,7)]h-alphaCGRP
      ([Cys(Et)(2,7)]h-alphaCGRP), a CGRP(2) receptor agonist, on human isolated middle
      meningeal artery segments, precontracted with KCl. Classical Schild plot analysis
      was used to characterise the receptor population in this artery using BIBN4096BS
      and h-alphaCGRP(8-37) as antagonists. h-alphaCGRP relaxed arterial segments more
      potently than [Cys(Et)(2,7)]h-alphaCGRP (pEC(50): 8.51+/-0.16 and 7.48+/-0.24,
      respectively), while the maximal responses to these agonists were not
      significantly different. BIBN4096BS equipotently blocked the relaxations induced
      by both agonists with a pA(2) of approximately 10 and with a Schild plot slope
      not significantly different from unity. h-alphaCGRP(8-37) also antagonised the
      response to h-alphaCGRP with a pA(2) of 6.46+/-0.16 and a Schild plot slope not
      different from unity. Furthermore, the results obtained from RT-PCR studies
      confirmed the presence of all the essential components required for a functional
      CGRP(1) receptor in these arteries. Considering the high antagonist potency of
      BIBN4096BS, coupled to the lower agonist potency of [Cys (Et)(2,7)]h-alphaCGRP,
      it is reasonable to suggest a predominant role of CGRP(1) receptors in the human
      middle meningeal artery. This view is reinforced by Schild plot analysis, which
      revealed a slope of unity in all experiments, giving further evidence for a
      homogeneous CGRP receptor population in this vascular preparation.

PMID- 16458931
TI  - Development of dry powder inhalation system of novel vasoactive intestinal
      peptide (VIP) analogue for pulmonary administration.
AB  - Vasoactive intestinal peptide (VIP) exerts a relaxing action on tracheal smooth
      muscle which is mediated through interaction with VIP receptors. The deficiency
      of VIP in the airways has been implicated in the pathogenesis of asthma. Thus,
      the administration of VIP may be useful for the therapy of pulmonary diseases.
      However, the therapeutic application of VIP is largely limited by its rapid
      degradation in addition to the systemic adverse effects due to the wide
      distribution of VIP receptors. To overcome these problems, we succeeded to
      synthesize a novel VIP derivative of VIP, [R15, 20, 21, L17]-VIP-GRR (IK312532),
      and to prepare its dry powder for the topical administration to the lung. The
      physicochemical properties of dry powder were evaluated by laser diffraction and
      cascade impactor. The laser diffraction analysis indicated that the carrier and
      fine particles had median diameter of 65.6 and 4.5 microm, respectively, and the
      air flow at the pressure of 0.15 MPa or higher resulted in the high dispersion
      and significant separation of fine particle containing peptide from the carrier
      molecule. The cascade impactor analysis clearly showed the high emission of dry
      powder from capsule and the deposition of peptide on stages 3 of the cascade
      impactor. The intratracheal administration of dry powder inhaler (DPI) of VIP or
      IK312532 brought about a significant decrease of maximal number of binding sites
      (Bmax) for [125I]VIP in anterior and posterior lobes of rat right lung,
      suggesting a significant occupancy of lung VIP receptors. This effect by IK312532
      DPI compared with VIP-DPI lasted for a longer period. Thus, IK312532-DPI may be a
      pharmacologically useful drug delivery system for the VIP therapy of pulmonary
      diseases such as asthma.

PMID- 16458932
TI  - Effects of acute and chronic nicotine on elevated plus maze in mice: involvement
      of calcium channels.
AB  - The current experiments examined the anxiety-related effects of acute and
      repeated nicotine administration using the elevated plus maze test in mice.
      Nicotine (0.1 mg/kg s.c., 5 and 30 min after injection; 0.5 mg/kg, s.c., 5 min
      after injection) had an anxiogenic effect, shown by specific decreases in the
      percentage of time spent on the open arms and in the percentage of open arm
      entries. Tolerance developed to this anxiogenic action after 6 days of daily
      nicotine administration (0.1 mg/kg, s.c.). Five minutes after the seventh
      injection, an anxiolytic effect was observed, i.e., specific increases in the
      percentage of time spent on the open arms and in the percentage of open arm
      entries. L-type voltage-dependent calcium channel antagonists nimodipine (5 and
      10 mg/kg, i.p.), flunarizine (5 and 10 mg/kg, i.p.), verapamil (5, 10, 20 mg/kg)
      and diltiazem (5, 10, 20 mg/kg, i.p.) were also injected prior to an acute low
      dose of nicotine or to each injection of chronic nicotine. Our results revealed
      that calcium channel blockers dose-dependently attenuated both an anxiogenic
      effect of nicotine as well as the development of tolerance to this effect. Our
      results suggest that neural calcium-dependent mechanisms are involved in the
      anxiety-related responses to acute and chronic nicotine injection that may
      ultimately lead to addiction and smoking relapse in human smokers.

PMID- 16458933
TI  - NT-1, an active constituent extracted from Tiaoxin Recipe, enhances long-term
      potentiation of CA1 subfield in rat hippocampal slices.
AB  - Previous studies demonstrated that Tiaoxin Recipe (TXR), a traditional Chinese
      medicinal prescription, could alleviate cognitive dysfunction. NT-1, an active
      constituent isolated from this prescription under guidance of bioactive
      evaluation, was preliminarily proved to enhance the ability of spatial learning
      and memory in rats. In the present study, using hippocampal slice preparations,
      we investigated the mechanisms by which NT-1 improves cognitive dysfunction
      contributed to corticosterone (CORT). NT-1 ameliorated the inhibition of LTP by
      CORT more significantly than TXR did. These results suggested that enhancing LTP
      induction is one mechanism by which NT-1 improves spatial learning and memory
      impaired by CORT.

PMID- 16458934
TI  - Involvement of AE3 isoform of Na(+)-independent Cl(-)/HCO(3)(-) exchanger in
      myocardial pH(i) recovery from intracellular alkalization.
AB  - Myocardial pH(i) recovery from intracellular alkalization results in part from
      the acid load (-J(H+)) carried by Cl(-)/HCO(3)(-) anion-exchangers (AE). Three AE
      isoforms, AE1, AE2 and AE3, have been identified in cardiac membranes, but the
      function of each isoform on pH(i) homeostasis is still under investigation. This
      work explored, by means of specific antibodies, the role of AE3 isoform in
      myocardial pH(i) regulation. We developed rabbit polyclonal antibodies against
      the extracellular "loops": one connecting the fifth to sixth and the other one
      the seventh to eighth transmembrane domains (loops 3 and 4, respectively) of AE3,
      and their effect on pH(i) regulation was studied in rat papillary muscles. The
      anti-AE3 loop 3 antibody decreased -J(H+) in response to myocardial alkalization
      (from a mean control value of 1.06+/-0.26 to 0.32+/-0.13 mmol/L/min, n=7, P<0.05)
      without affecting the baseline pH(i) (7.22+/-0.03 vs. 7.21+/-0.04). The anti-AE3
      loop 4 antibody did not modify either pH(i) recovery or baseline pH(i). Under
      control conditions, endothelin-1 (ET-1) increased -J(H+) in response to
      myocardial alkalization from 1.30+/-0.18 to 2.01+/-0.33 mmol/L /min (n=5,
      P<0.05). This effect of ET-1 on -J(H+) was abolished by anti-AE3 loop 3 antibody.
      In addition, the MgATP-induced stimulation of AE activity was reduced by the anti
      AE3 loop 3 antibody. These data support the key role of the AE3 isoform in
      myocardial pH(i) recovery from alkaline loads and also in the stimulatory effect
      of ET-1 on AE activity. To a lesser extent, it may also contribute to the effect
      of MgATP on pH(i).

PMID- 16458935
TI  - Monitoring the gene expression profiles of doxorubicin-resistant acute myelocytic
      leukemia cells by DNA microarray analysis.
AB  - Acquired drug-resistance phenotype is a key factor in the relapse of patients
      suffering hematological malignancies. In order to investigate the genes involved
      in drug resistance, a human leukemia cell line that is resistant to doxorubicin,
      an anthracycline anticancer agent (AML-2/DX100), was selected and its gene
      expression profile was analyzed using a cDNA microarray. A number of genes were
      differentially expressed in the AML-2/DX100 cells, compared with the wild type
      (AML-2/WT). Pro-apoptotic genes such as TNFSF7 and p21 (Cip1/Waf1) were
      significantly down-regulated, whereas the IKBKB, PCNA, stathmin 1, MCM5, MMP-2
      and MRP1 genes, which are involved in anti-apoptotic or cell cycle progression,
      were over-expressed. The AML-2/DX100 cells were also resistant to other
      anticancer drugs, including daunorubicin and camptothecin, and the expression
      levels of the differentially regulated genes such as STMN1, MMP-2 and CTSG, were
      constantly maintained. This suggests that the deregulated genes obtained from the
      DNA microarray analysis in a cell line model of drug resistance might contribute
      to the acquired drug resistance after chronic exposure.

PMID- 16458937
TI  - Bi-phasic activation of eNOS in response to uni-axial cyclic stretch is mediated
      by differential mechanisms in BAECs.
AB  - We investigated the signaling mechanism of stretch-induced NO (Nitric oxide)
      production in bovine arterial endothelial cells (BAECs). BAECs cultured on an
      elastic silicone chamber coated with fibronectin were subjected to uni-axial
      cyclic stretch (1 Hz, 20% in length) and the amount of produced NO was measured
      by a cGMP assay. NO production increased in a bi-phasic manner and peaked at 5
      min and 20 min after stretch onset. Correspondingly, the activities of
      endothelial nitric oxide synthase (eNOS) and Akt/PKB (measured by phosphorylation
      at serine 1,177 and serine 473, respectively), showed two peaks over time.
      Application of Gd(3+), a potent SA channel blocker, and depletion of external
      Ca(2+) exclusively inhibited the first peaks of eNOS and Akt activity, but
      exerted little effect on the second peak. On the other hand, the PI3K inhibitors,
      Wortmannin, LY294002, almost completely inhibited the second peak but not the
      first. These results suggest that up-regulation of eNOS in response to cyclic
      stretch was mediated by two distinct pathways, [Ca(2+)](i) increases via the SA
      channel in an early phase (partially Akt/PKB), and PI3K-Akt/PKB pathways in a
      late phase.

PMID- 16458938
TI  - The complement C5b-9 complexes induced injury of glomerular mesangial cells in
      rats with Thy-1 nephritis by increasing nitric oxide synthesis.
AB  - Thy-1 nephritis (Thy-1 N), namely, anti-Thy-1 or anti-thymocyte serum (ATS)
      induced nephritis (ATSN), is a typical model of human mesangioproliferative
      glomerulonephritis. The pathologic changes of glomerular mesangial cells (GMCs)
      in Thy-1 N are complement-dependent, especially C5b-9 complexes, but the role of
      C5b-9 in the mechanism of Thy-1 N has not been defined. Because previous studies
      have demonstrated that sublytic C5b-9 can increase production of several
      inflammatory mediators from resident glomerular cells, we utilized the isolated
      human membrane-bound C5b-9 complexes to stimulate the cultured rat GMCs and
      examined whether the GMCs can also induce the synthesis of nitric oxide (NO) in
      vitro. Simultaneously, the effects of antiserum against rat C5b-9 and NG
      monomethyl-L-arginine (L-NMMA, NO inhibitor), including interfering with the
      formation of C5b-9, reducing NO production and GMCs injury were observed. The
      results showed that sublytic C5b-9 can increase synthesis of inducible NO from
      the stimulated GMCs, and that the anti-C5b-9 antiserum can obviously inhibit the
      pathologic changes in Thy-1 N, while L-NMMA can decrease the GMCs damage although
      the effect is not so significant as that of the anti-C5b-9 antiserum. These
      findings indicate that the synthesis of NO by GMCs can be promoted by sublytic
      C5b-9, and that lesions of GMCs in rats with Thy-1 N are prevented by either
      inhibiting C5b-9 formation or NO elevation in advance. The pathologic changes of
      GMCs in Thy-1 N are indeed complement C5b-9-dependent, and the glomerular injury
      can be mediated in part through elevation of NO from the GMCs after the sublytic
      C5b-9 stimulation.

PMID- 16458939
TI  - Effects of multiple perturbations on the survivorship of fragments of three coral
      species.
AB  - Fist-sized fragments of Porites cylindrica, Porites rus and Pavona frondifera
      were deployed in single-species (P. cylindrica) and mixed-species (all three)
      plots in a shallow reef area in the northwestern Philippines. After 6 months, the
      corals in half of the plots were broken into smaller pieces to simulate an
      episodic physical disturbance. The survival of all corals was monitored from
      March 2000 to July 2001 during which the corals experienced 2 typhoons and
      episodes of algal overgrowth. For both intact and broken treatments, there was
      significantly higher survival in the mixed-species plots than in the single
      species treatments. Fragment mortality varied between disturbances of varying
      frequencies and magnitudes, namely: one-time fragmentation stress, seasonal
      overgrowth by cyanobacteria and macroalgae, short-term (1 day) and long-term
      (more than 1 week) burial. The mixed-species assemblages had higher fragment
      survivorship than the monospecific assemblages during small-scale perturbations
      (e.g., algal overgrowth), but not in the face of subsequent, larger scale
      disturbances. This study emphasizes that coral responses to disturbance are both
      species- and context-specific.

PMID- 16458936
TI  - Tocotrienols: Vitamin E beyond tocopherols.
AB  - In nature, eight substances have been found to have vitamin E activity: alpha-,
      beta-, gamma- and delta-tocopherol; and alpha-, beta-, gamma- and delta
      tocotrienol. Yet, of all papers on vitamin E listed in PubMed less than 1% relate
      to tocotrienols. The abundance of alpha-tocopherol in the human body and the
      comparable efficiency of all vitamin E molecules as antioxidants, led biologists
      to neglect the non-tocopherol vitamin E molecules as topics for basic and
      clinical research. Recent developments warrant a serious reconsideration of this
      conventional wisdom. Tocotrienols possess powerful neuroprotective, anti-cancer
      and cholesterol lowering properties that are often not exhibited by tocopherols.
      Current developments in vitamin E research clearly indicate that members of the
      vitamin E family are not redundant with respect to their biological functions.
      alpha-Tocotrienol, gamma-tocopherol, and delta-tocotrienol have emerged as
      vitamin E molecules with functions in health and disease that are clearly
      distinct from that of alpha-tocopherol. At nanomolar concentration, alpha
      tocotrienol, not alpha-tocopherol, prevents neurodegeneration. On a concentration
      basis, this finding represents the most potent of all biological functions
      exhibited by any natural vitamin E molecule. An expanding body of evidence
      support that members of the vitamin E family are functionally unique. In
      recognition of this fact, title claims in manuscripts should be limited to the
      specific form of vitamin E studied. For example, evidence for toxicity of a
      specific form of tocopherol in excess may not be used to conclude that high
      dosage "vitamin E" supplementation may increase all-cause mortality. Such
      conclusion incorrectly implies that tocotrienols are toxic as well under
      conditions where tocotrienols were not even considered. The current state of
      knowledge warrants strategic investment into the lesser known forms of vitamin E.
      This will enable prudent selection of the appropriate vitamin E molecule for
      studies addressing a specific need.

PMID- 16458940
TI  - Central gustatory lesions and learned taste aversions: unconditioned stimuli.
AB  - The efficacy of two different unconditioned stimuli (US) in producing conditioned
      taste aversion (CTA) was tested in rats after bilateral ibotenic acid (IBO)
      lesions of the gustatory nucleus of thalamus (TTAx) and the medial and lateral
      parabrachial nuclei (mPBNx, lPBNx). An initial study determined an equivalent
      dose for the two USs, LiCl and cyclophosphamide (CY), using non-lesioned rats.
      Subsequently, using a separate set of lesioned animals and their sham controls
      (SHAM), injections of CY were paired 3 times with one of two taste stimuli (CSs),
      0.1 M NaCl for half the rats in each group, 0.2 M sucrose for the other half.
      After these conditioning trials, the CS was presented twice more without the US,
      first in a 1-bottle test, then in a 2-bottle choice with water. The acquisition
      and test trials had 2 intervening water-only days to assure complete rehydration.
      Two weeks later, the same rats were tested again for acquisition of a CTA using
      LiCl as the US and the opposite CS as that used during the CY trials. The SHAM
      and TTAx groups learned to avoid consuming the taste associated with either CY or
      LiCl treatment. The two PBNx groups failed to learn an aversion regardless of the
      US.

PMID- 16458941
TI  - An angiotensin-I converting enzyme inhibitor from buckwheat (Fagopyrum esculentum
      Moench) flour.
AB  - A compound that inhibited angiotensin-I converting enzyme (ACE) activity was
      isolated from buckwheat powder. This compound is thought to be the hydroxy
      derivative of nicotianamine and its chemical structure is 2''
      hydroxynicotianamine. This compound showed a very high inhibitory activity toward
      ACE, and the IC(50) was 0.08 microM. Only this hydroxy analog was found in
      buckwheat powder, at about 30 mg/100g, and no nicotianamine was detected.
      However, nicotianamine was detected in the buckwheat plant body. 2''
      hydroxynicotianamine was also found in other polygonaceous plants.

PMID- 16458942
TI  - Polygalacturonase-inhibiting protein (PGIP) in plant defence: a structural view.
AB  - Polygalacturonase-inhibiting proteins are plant extracellular leucine-rich repeat
      proteins that specifically bind and inhibit fungal polygalacturonases. The
      interaction with PGIP limits the destructive potential of polygalacturonases and
      might trigger the plant defence responses induced by oligogalacturonides. A high
      degree of polymorphism is found both in PGs and PGIPs, accounting for the
      specificity of different plant inhibitors for PGs from different fungi. Here, we
      review the structural features and our current understanding of the PG-PGIP
      interaction.

PMID- 16458943
TI  - Salvidorol, a nor-abietane diterpene with a rare carbon skeleton and two abietane
      diterpene derivatives from Salvia dorrii.
AB  - Salvidorol (1), a irregular nor-abietane-type diterpene, was isolated from the
      aerial parts of Salvia dorrii, in addition to two epimeric abietane diterpenes (2
      and 3). This is the first report of a nor-diterpene with an irregular skeleton.
      The structures were established by high-field NMR techniques ((1)H-(1)H COSY,
      DEPT, HMQC, HMBC, NOESY and HRMS) and in case of 2 was confirmed by X-ray
      analysis.

PMID- 16458944
TI  - Unusual chromenes from Peperomia blanda.
AB  - From the methanol extract of the aerial parts of Peperomia blanda (Piperaceae),
      two chromenes were isolated and characterized mainly through application of 2D
      NMR spectroscopy. The structures were 2S-(4-methyl-3-pentenyl)-6-formyl-8-hydroxy
      2,7-dimethyl-2H-chromene and 2S-(4-methyl-3-pentenyl)-5-hydroxy-6-formyl-2,7
      dimethyl-2H-chromene named as blandachromenes I and II, respectively.

PMID- 16458945
TI  - Game theory and human evolution: a critique of some recent interpretations of
      experimental games.
AB  - Economists and psychologists have been testing Nash equilibrium predictions of
      game theory models of human behavior. In many instances, humans do not conform to
      the predictions. These results are of great interest to biologists because they
      also raise questions about well-known ESS models of cooperation. Cooperation in
      certain one-shot, anonymous interactions, and a willingness to punish others at a
      net cost to oneself are some of the most intriguing deviations from standard
      theory. One proposed explanation for these results that is receiving increasing
      attention invokes the cultural group selection of 'other regarding' social norms.
      We critically review this explanation. We conclude that experimental results
      reveal limits in two implicit models of cognitive structure commonly employed by
      economists and evolutionary biologists.

PMID- 16458947
TI  - Advances in distributed parameter approach to the dynamics and control of
      activated sludge processes for wastewater treatment.
AB  - This paper presents a review of modelling and control of biological nutrient
      removal (BNR)-activated sludge processes for wastewater treatment using
      distributed parameter models described by partial differential equations (PDE).
      Numerical methods for solution to the BNR-activated sludge process dynamics are
      reviewed and these include method of lines, global orthogonal collocation and
      orthogonal collocation on finite elements. Fundamental techniques and conceptual
      advances of the distributed parameter approach to the dynamics and control of
      activated sludge processes are briefly described. A critical analysis on the
      advantages of the distributed parameter approach over the conventional modelling
      strategy in this paper shows that the activated sludge process is more adequately
      described by the former and the method is recommended for application to the
      wastewater industry.

PMID- 16458946
TI  - A single amino acid substitution within the transmembrane domain of the human
      immunodeficiency virus type 1 Vpu protein renders simian-human immunodeficiency
      virus (SHIV(KU-1bMC33)) susceptible to rimantadine.
AB  - Previous studies from our laboratory have shown that the transmembrane domain
      (TM) of the Vpu protein of human immunodeficiency virus type 1 (HIV-1)
      contributes to the pathogenesis of SHIV(KU-1bMC33) in macaques and that the TM
      domain of Vpu could be replaced with the M2 protein viroporin from influenza A
      virus. Recently, we showed that the replacement of the TM domain of Vpu with that
      of the M2 protein of influenza A virus resulted in a virus (SHIV(M2)) that was
      sensitive to rimantadine [Hout, D.R., Gomez, M.L., Pacyniak, E., Gomez, L.M.,
      Inbody, S.H., Mulcahy, E.R., Culley, N., Pinson, D.M., Powers, M.F., Wong, S.W.,
      Stephens, E.B., 2006. Substitution of the transmembrane domain of Vpu in simian
      human immunodeficiency virus (SHIV(KU-1bMC33)) with that of M2 of influenza A
      results in a virus that is sensitive to inhibitors of the M2 ion channel and is
      pathogenic for pig-tailed macaques. Virology 344, 541-558]. Based on previous
      studies of the M2 protein which have shown that the His-X-X-X-Trp motif within
      the M2 is essential to the function of the M2 proton channel, we have constructed
      a novel SHIV in which the alanine at position 19 of the TM domain was replaced
      with a histidine residue resulting in the motif His-Ile-Leu-Val-Trp. The
      SHIV(VpuA19H) replicated with similar kinetics as the parental SHIV(KU-1bMC33)
      and pulse-chase analysis revealed that the processing of viral proteins was
      similar to SHIV(KU-1bMC33). This SHIV(VpuA19H) virus was found to be more
      sensitive to the M2 ion channel blocker rimantadine than SHIV(M2). Electron
      microscopic examination of SHIV(VpuA19H)-infected cells treated with rimantadine
      revealed an accumulation of viral particles at the cell surface and within
      intracellular vesicles, which was similar to that previously observed to SHIV(M2)
      infected cells treated with rimantadine. These data indicate that the Vpu protein
      of HIV-1 can be converted into a rimantadine-sensitive ion channel with the
      alteration of one amino acid and provide additional evidence that drugs targeting
      the Vpu TM/ion channel can be effective anti-HIV-1 drugs.

PMID- 16458948
TI  - Impacts of blending ground, surface, and saline waters on lead release in
      drinking water distribution systems.
AB  - The impacts of distribution water quality changes caused by blending different
      source waters on lead release from corrosion loops containing small lead coupons
      were investigated in a pilot distribution study. The 1-year pilot study
      demonstrated that lead release to drinking water increased as chlorides increased
      and sulfates decreased. Silica and calcium inhibited lead release to a lesser
      degree than sulfates. An additional 3-month field study isolated and verified the
      effects of chlorides and sulfates on lead release. Lead release decreased with
      increasing pH and increasing alkalinity during the 1-year pilot study; however,
      the effects of pH and alkalinity on lead release, were not clearly elucidated due
      to confounding effects. A statistical model was developed using nonlinear
      regression, which showed that lead release increased with increasing chlorides,
      alkalinity and temperature, and decreased with increasing pH and sulfates. The
      model indicated that primary treatment processes such as enhanced coagulation and
      RO (reverse osmosis membrane) were related to lead release by water quality.
      Chlorides are high in RO-finished water and increase lead release, while sulfates
      are high following enhanced coagulation and decrease lead release.

PMID- 16458949
TI  - Changes of physical and biochemical properties of Cryptosporidium oocysts with
      various storage conditions.
AB  - Physical and biochemical properties of Cryptosporidium parvum oocyst were
      examined after storage under various conditions. Oocyst-positive-fecal samples
      recovered from calves were either stored in a 2.0% potassium dichromate solution
      (Cr) or deionized water (W), or kept as a fecal pellet (P), and stored at 4 or 18
      degrees C for a maximum of 100 days. When stored in Cr at 4 degrees C, the
      morphology of oocysts and their ability to withstand ultrasonics was not affected
      by the storing media or the storage period. However, when stored at 18 degees C
      as a fecal pellet, the specific gravity of the oocysts increased and a
      significant decrease in the oocysts resistance to ultrasonics occurred. These
      changes in oocyst properties may affect the performance of methods used to detect
      oocysts in water samples. When using the current test methods or when developing
      a new test method, it is important to take these factors into consideration.

PMID- 16458950
TI  - Comparative performance of membrane filters vs. high-surface area filtration
      cartridges for the determination of element concentrations in freshwater systems.
AB  - Interdisciplinary studies on trace element cycles in aquatic environments may
      require the simultaneous use of small- and large-scale filtration devices to
      collect all the necessary sample aliquots for the different scientific objectives
      (e.g. trace element and organic carbon analysis, chronic toxicity testing, and
      characterization of colloidal matter). This study compares the performance of
      membrane filters (MF, Millipore-approx. surface area 0.002 m2) and two large
      surface area filtration cartridges (Calyx, MSI and Polypro, CUNO approx. surface
      area 1 m2) in three freshwater systems with contrasting characteristics. Membrane
      filters and filtration cartridges fractionate water samples in a comparable way
      except for some elements (Al, Mn, Pb, and Ti) and when dealing with high
      turbidity, organic-rich matrices. Estimation of the actual filters' pore size
      using the single particle counting technique gives cut-offs of 0.2-0.3, 0.7 and 2
      microm for membrane filters, Polypro cartridge and Calyx cartridge respectively,
      explaining many of the differences observed between membrane and cartridge
      filters. Direct involvement of filter manufacturers to determine actual filter
      cut-offs during environmental applications would be highly beneficial to increase
      the comparability of the measurements of filterable element concentrations.
      Better harmonization of filtration procedures (filter type, actual filter cut
      off, in situ vs. ex situ filtration) among laboratories in different countries is
      also necessary in order to improve consistency of environmental databases.

PMID- 16458951
TI  - Passive sampler derived air concentrations of PBDEs along an urban-rural
      transect: spatial and temporal trends.
AB  - Passive air samplers consisting of polyurethane foam (PUF) disks housed in
      chambers were deployed at several sites along a approximately 75 km urban-rural
      gradient in Toronto and analyzed for polybrominated diphenyl ethers (PBDEs).
      Samplers were allowed to integrate gas-phase PBDEs over three consecutive seasons
      starting in the summer of 2000. PBDEs were fairly uniform along the transect with
      air concentrations in Toronto (10-30 pgm(-3)) about a factor of two greater than
      at rural sites. Lowest concentrations were observed during the winter and
      probably associated with reduced inputs from indoor sources of PBDEs and to a
      preference for PBDEs to partition to the particle-phase at colder temperatures.
      The composition of PBDEs in the air samples did not differ across the transect or
      for the different seasons.

PMID- 16458952
TI  - Environmental contamination at Finnish shooting ranges--the scope of the problem
      and management options.
AB  - In Finland, shooting ranges are among the most common activities causing soil
      contamination. According to our study based on questionnaires and previous
      regional surveys, the total number of Finnish outdoor shooting ranges is between
      2000 and 2500. Most of the ranges are small and only ca. 5% exceed 20 ha. Almost
      a third of the ranges can cause a groundwater pollution risk, while only few
      cause an immediate health risk. In the first instance, 50-60 shooting ranges
      identified as being high-risk areas should be investigated in detail. At present,
      the risk management options at Finnish shooting ranges are very limited. Hence,
      soil excavation combined with disposal is the most common remediation technique.
      Some of the remediation methods used in other countries have been proven
      unsuitable in Finnish conditions. Therefore, new, feasible, cost-effective and
      economical remediation technologies are needed. To exclude future contamination,
      a total ban of lead shot would be the most effective way.

PMID- 16458953
TI  - The effects of social isolation on neuropeptide Y levels, exploratory and anxiety
      related behaviors in rats.
AB  - NPY is one of the most abundantly expressed peptides within the CNS, and has been
      previously demonstrated to be altered in several animal models of depression, as
      well as to be differentially regulated by acute and repeated stress. The effect
      of social deprivation, through isolation housing, on brain NPY concentrations in
      adult rats has not been previously investigated. The effects of 12 weeks of
      social isolation, in adult rats, on anxiety-related behaviors and central
      concentrations of NPY in: hypothalamus, amygdala, caudate-putamen, hippocampus,
      and frontal cortex were evaluated. Single housed animals spent significantly more
      time on the open arms of the elevated plus maze and in the central area of the
      open field as compared to pair housed controls. These data are most likely
      indicative of enhanced exploration and novelty seeking. Concentrations of
      neuropeptide Y were increased in the caudate-putamen of the single housed
      subjects. NPY levels in caudate/putamen and hypothalamus were also significantly
      correlated with time spent in the open arms of the elevated plus maze. These data
      suggest that chronic social isolation, in these adult Wistar rats, did not
      increase anxiety but produced enhanced exploration in tests of anxiety, an effect
      that was associated with NPY concentrations in the striatum and hypothalamus.

PMID- 16458954
TI  - Antinociceptive properties of the ethanolic extract and of the triterpene
      3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of
      Combretum leprosum in mice.
AB  - The present study examined the antinociceptive effects of the ethanolic extract
      (EE) and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained
      from the flowers of Combretum leprosum in chemical and thermal behavioural models
      of pain in mice. The EE (10-1000 mg/kg) given orally (p.o.), 1 h prior to
      testing, produced dose-dependent inhibition of acetic acid-induced visceral pain,
      with mean ID50 value of 131.9 mg/kg. In the formalin test, the EE (10-300 mg/kg,
      p.o.) also caused significant inhibition of both the early (neurogenic pain) and
      the late (inflammatory pain) phases of formalin-induced licking, however, it was
      more potent and efficacious in relation to the late phase of the formalin test,
      with mean ID50 values for the neurogenic and the inflammatory phases of
      approximately 300 and 88.8 mg/kg, respectively. The EE (10-1000 mg/kg, p.o.) also
      caused significant and dose-dependent inhibition of capsaicin- and glutamate
      induced pain, with mean ID50 values of 160.5 and 38.3 mg/kg, respectively.
      Furthermore, the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene (1-30
      mg/kg), given p.o., 1 h prior to testing, also produced dose-related inhibition
      of glutamate-induced pain, with a mean ID50 value of 5.6 mg/kg. When assessed in
      a thermal model of pain, the EE (10-300 mg/kg, p.o.) and fentanyl (100 microg/kg,
      s.c.) caused a significant and marked increase in the latency response on the hot
      plate test (50 degrees C). The antinociception caused by EE (100 mg/kg, p.o.) in
      the glutamate test was significantly attenuated by intraperitoneal (i.p.)
      treatment of mice with naloxone (opioid receptor antagonist, 1 mg/kg), pindolol
      (a 5-HT 1A/1B receptor/beta adrenoceptor antagonist, 1 mg/kg), WAY100635 (a 5-HT
      1A receptor antagonist, 0.7 mg/kg) or ketanserin (a 5-HT 2A receptor antagonist,
      0.3 mg/kg). In contrast, EE (100 mg/kg, p.o.) antinociception was affected
      neither by L-arginine (precursor of nitric oxide, 600 mg/kg) nor by ondansetron
      (a 5-HT3 receptor antagonist, 0.5 mg/kg) i.p. treatment. It was not associated
      with non-specific effects such as muscle relaxation or sedation. Together, these
      results indicate that EE produces dose-related antinociception in several models
      of chemical and thermal pain through mechanisms that involve an interaction with
      opioid and serotonergic (i.e., through 5-HT 1A/1B and 5-HT 2A receptors) systems.

PMID- 16458955
TI  - Fit for Life Boy Scout badge: outcome evaluation of a troop and Internet
      intervention.
AB  - BACKGROUND: This study reports the results of a 9-week intervention on the
      physical activity levels of adolescent males. METHODS: Participants were 473 10-
      to 14-year-old Houston Boy Scouts (42 troops) with troops randomly assigned to
      intervention or control conditions. Data were collected in spring (16 troops) and
      fall (26 troop) waves during 2003. Intervention participants received a 9-week
      troop and Internet program to increase physical activity skills, self-efficacy
      and goal-setting. Physical activity was assessed at baseline, end of the
      intervention (Post#1) and post-6 months (Post#2) by accelerometer. Minutes of
      sedentary, light and moderate to vigorous physical activity were calculated.
      Repeated measure analyses were performed to test differences in physical activity
      over time between groups with participants nested in troops. RESULTS: A three-way
      interaction (group * time * wave) that approached significance (P = 0.051)
      indicated a 12-min reduction in sedentary behavior among spring intervention
      participants. A significant three-way interaction (P = 0.011) (group * time *
      wave) indicated a 12-min increase in light intensity activity among the spring
      intervention group. CONCLUSION: Participation in the Fit for Life badge program
      resulted in a trend towards a small decrease in sedentary behavior and increased
      light intensity physical activity among spring participants only. There was no
      effect on moderate to vigorous physical activity.

PMID- 16458956
TI  - Weight perception and weight-related sociocultural and behavioral factors in
      Chinese adolescents.
AB  - BACKGROUND: Rapid economic development accompanied by imported Western media,
      advertising, fashion, and lifestyle in mainland China has resulted in shifts in
      cultural beliefs and beauty ideals in adolescents. The present study focused on
      understanding relationships among weight perception and weight-related
      sociocultural and behavioral factors in Chinese adolescents. METHODS: Data
      collected in 2002 from 6863 middle and high school students and their parents
      from four large cities in mainland China were used. Weight status was determined
      by measured weight and height. Weight perception, media exposure, attitudes, and
      health behaviors were assessed by a structured questionnaire survey. RESULTS:
      Boys were more likely to describe themselves as either too thin or relatively
      thin than girls (37.32% vs. 18.79%), while girls more often considered themselves
      either relatively heavy or too heavy than boys (50.83% vs. 26.54%). Girls who
      were actually normal or underweight were more likely than boys to describe
      themselves as either relatively heavy or very heavy (41.6% vs. 11.6%), while boys
      who were actually normal or overweight were more likely than girls to believe
      themselves as underweight (30.9% vs. 15.7%). Girls who were frequently exposed to
      media from Japan, Korea, Hong Kong, and Taiwan, and placed high value on their
      physical appearance, were more likely to be dissatisfied with their body weight,
      which in turn were more likely to restrict consumption of certain foods, smoke
      cigarettes, and drink alcohol. Similar results were not observed in boys.
      CONCLUSIONS: Weight dissatisfaction was prevalent in Chinese adolescents and was
      significantly related to media exposure, attitudes towards physical appearance,
      and adoption of certain health-risk behaviors in girls. Our findings underscore
      the importance of sociocultural influences in shaping realistic body image and
      have implications for prevention and early intervention for establishing health
      behavioral practices during adolescence.

PMID- 16458957
TI  - Active cigarette smoking, household passive smoke exposure, and the risk of
      developing pancreatic cancer.
AB  - OBJECTIVE: The objective of this study was to examine the association between
      active cigarette smoking, household passive smoke exposure, and pancreatic cancer
      risk using a prospective cohort design. METHODS: Two cohorts were established in
      Washington County, Maryland in 1963 (n = 45,749) and 1975 (n = 48,172). The
      Washington County Cancer Registry was used to ascertain the occurrence of
      pancreatic cancer in the 1963 cohort from 1963-1978 and in the 1975 cohort from
      1975-1994. Poisson regression was used to analyze the associations between active
      smoking and household passive smoke exposure and pancreatic cancer risk. RESULTS:
      Current active smoking was associated with a two-fold increased risk of
      pancreatic cancer in both cohorts. Among never-smokers in each cohort, exposure
      to household passive smoke was not associated with an increased risk of
      pancreatic cancer, although the confidence limits were wide due to a small number
      of cases. CONCLUSIONS: This study further documents the approximate doubling of
      pancreatic cancer risk in current active smokers. Our results also indicate that
      household passive smoke exposure is not associated with pancreatic cancer risk,
      although our risk estimates lacked precision.

PMID- 16458958
TI  - Combination dopamine agonist and prostaglandin agonist treatment of cystic
      endometrial hyperplasia-pyometra complex in the bitch.
AB  - Cystic endometrial hyperplasia-pyometra (CEH-P) complex is a progesterone
      dependent disease that requires medical treatment in bitches intended for
      breeding. To test the efficacy and safety of a combined protocol and to assess
      the effect of age, stage of cycle, previous steroid hormone administration and
      parity on treatment, 29 bitches diagnosed with CEH-P complex were treated daily
      with cabergoline 5 microg/kg PO and cloprostenol 1 microg/kg SC for 7-14 days,
      along with supportive antibiotic and hydration therapies. Before treatment, and
      on Days 3, 7 and 14, all bitches were evaluated clinically and uterine horn
      diameter measured during trans-abdominal ultrasonography. Twenty-four of 29
      bitches were cured by either Day 7 or 14. Nine bitches had mild digestive side
      effects. Clinical signs related to pyometra began to improve markedly as early as
      Day 2 of treatment. Uterine diameters decreased (P < 0.05) by Day 3 of treatment,
      and continued to gradually decrease, reaching normal size by Day 14. Relapses
      occurred in 6 of 29 cases. Pregnancy was achieved in one of the two young bitches
      bred after treatment. No significant relationships were found between success
      rate and age, stage of the estrous cycle, previous hormone administration or
      parity. Although no variables affecting treatment results could be identified,
      this combination of compounds was found to be an efficient and safe for treatment
      of CEH-P.

PMID- 16458959
TI  - The effect of hyaluronan concentrations in hST-supplemented TCM 199 on in vitro
      nuclear maturation of bitch cumulus-oocyte complexes.
AB  - In this study, the effect of hyaluronan (HA) on in vitro nuclear maturation of
      bitch oocytes was evaluated. Cumulus-oocyte complexes (COCs) were cultured for 48
      h at 37 degrees C in a humidified atmosphere of 5% CO2 in air. Oocytes with one
      or more layers of intact cumulus cells and dark cytoplasm were allocated to the
      following treatments: (A) TCM 199 supplemented with 25 mM Hepes/L (v/v), with 10%
      heat inactivated estrous cow serum (ECS), 50 microg/mL gentamycin, 2.2 mg/mL
      sodium bicarbonate, 22 microg/mL pyruvic acid, 20 microg/mL estradiol, 0.5
      microg/mL FSH, 0.03 IU/mL hCG and 1 microg/mL human somatotropin (hST) (control
      medium), (B) Treatment A + 0.5 mg/mL HA and (C) Treatment A + 1.0 mg/mL HA.
      Supplementation with HA did not increase the number of oocytes that resumed
      meiosis. Additionally, there were no differences among treatments in the cumulus
      cell expansion of oocytes. In conclusion, the addition of HA to hST-supplemented
      TCM 199 did not improve the in vitro nuclear maturation of bitch oocytes, and
      therefore appeared to be unsatisfactory as supplement for in vitro maturation
      (IVM) of canine oocytes.

PMID- 16458960
TI  - Protein phosphatase inhibitor-1 (PPI-1) has protective activities in stress
      conditions in E. coli.
AB  - Protein phosphatase inhibitor-1 (PPI-1) is a major inhibitor of protein
      phosphatase 1 (PP1), which regulates signal transduction in many eukaryotic
      cellular processes. Biophysical studies have shown that PPI-1 has a large Stokes
      radius and is heat stable, suggesting that it lacks extensive secondary
      structures. The unfolded structure of PPI-1 may enable it to interact with many
      proteins or ligands during stress conditions. Here we show that PPI-1 can act as
      a protective molecule, inhibiting protein aggregation and guarding E. coli cells
      against various stresses. Therefore, PPI-1 seems to have a physiological function
      as a protective molecule as well as regulator of protein serine/threonine
      phosphatases.

PMID- 16458961
TI  - Electrospun silk-BMP-2 scaffolds for bone tissue engineering.
AB  - Silk fibroin fiber scaffolds containing bone morphogenetic protein 2 (BMP-2)
      and/or nanoparticles of hydroxyapatite (nHAP) prepared via electrospinning were
      used for in vitro bone formation from human bone marrow-derived mesenchymal stem
      cells (hMSCs). BMP-2 survived the aqueous-based electrospinnig process in
      bioactive form. hMSCs were cultured for up to 31 days under static conditions in
      osteogenic media on the scaffolds (silk/PEO/BMP-2, silk/PEO/nHAP,
      silk/PEO/nHAP/BMP-2) and controls (silk/PEO, silk/PEO extracted). Electrospun
      silk fibroin-based scaffolds supported hMSC growth and differentiation toward
      osteogenic outcomes. The scaffolds with the co-processed BMP-2 supported higher
      calcium deposition and enhanced transcript levels of bone-specific markers than
      in the controls, indicating that these nanofibrous electrospun silk scaffolds
      were an efficient delivery system for BMP-2. X-ray diffraction (XRD) analysis
      revealed that the apatite formed on the silk fibroin/BMP-2 scaffolds had higher
      crystallinity than on the silk fibroin scaffold controls. In addition, nHAP
      particles were incorporated into the electrospun fibrous scaffolds during
      processing and improved bone formation. The coexistence of BMP-2 and nHAP in the
      electrospun silk fibroin fibers resulted in the highest calcium deposition and
      upregulation of BMP-2 transcript levels when compared with the other systems. The
      results suggest that electrospun silk-fibroin-based scaffolds are potential
      candidates for bone tissue engineering. Furthermore, the mild aqueous process
      required to spin the fibers offers an important option for delivery of labile
      cytokines and other components into the system.

PMID- 16458962
TI  - Two germ line polymorphisms of the tumour suppressor gene p53 may influence the
      biology of chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is characterised by the accumulation of
      mature B lymphocytes. Defects in the tumour suppressor gene p53 pathway are known
      to be important in CLL and p53 inactivation is associated with a particularly
      aggressive form of CLL. A single nucleotide polymorphism (SNP) in codon 72 of
      TP53 leads to a single amino acid change leading to a change in apoptotic
      potential and alters prognosis in squamous carcinomas. A polymorphism within
      intron 6 of TP53 has been postulated to alter the susceptibility to lung cancer.
      Our study looked at the influence of these two polymorphisms in a cohort of
      approximately 200 CLL patients. The codon 72 polymorphism A2/A2 genotype
      (homozygous arginine) was associated with an increased susceptibility to CLL and
      CD38 negativity but did not appear to influence other biological behaviour or
      clinical response. The intron 6 polymorphism A2/A2 genotype was strongly
      associated with early stage disease, CD38 negativity and a longer time to first
      treatment. The effect on time to treatment did not retain significance in
      multivariate analysis and the polymorphism did not predict for overall survival
      (OS). Detailed investigation of the complete TP53 genotype is warranted to
      further characterise the role of SNPs in p53 and their influence on CLL.

PMID- 16458963
TI  - Effective plasmid pX3 transduction in Lactobacillus delbrueckii by bacteriophage
      LL-H.
AB  - High-frequency plasmid transductions in Lactobacillus delbrueckii subsp. lactis
      and subsp. bulgaricus strains mediated by pac-type bacteriophages were observed
      and further investigated. The frequency of plasmid transduction by phages LL-H
      and LL-S attained levels of from 0.10 to about 1 with plasmid p X 3, but only
      about 2 x 10(-2) with plasmid pJK650. Infection of L. delbrueckii subsp. lactis
      strain LKT(pX3) or ATCC 15808(pX3) with phage LL-H resulted in intensive
      concatemerization of plasmid pX3, and most progeny phage particles contained
      concatemers of plasmid DNA instead of phage LL-H DNA. The synthesis of phage LL-H
      DNA was depressed. No evident homology or recombination was observed between
      phage LL-H DNA and plasmid pX3. The unusually high frequency of plasmid pX3
      transduction by phage LL-H could be considered to result from specific
      interaction(s) between a particular phage and plasmid. These interactions may
      include pX3-mediated blockage of phage LL-H DNA replication and effective use of
      a particular pac-like site located about 1 kb from BglII in the smaller NdeI
      BglII fragment of plasmid pX3. Phage LL-H together with plasmid vector pX3 could
      be used as effective plasmid transduction tools for genetic engineering of L.
      delbrueckii subsp. lactis and subsp. bulgaricus strains.

PMID- 16458964
TI  - Efficacy of latanoprost or fixed-combination latanoprost-timolol in patients
      switched from a combination of timolol and a nonprostaglandin medication.
AB  - PURPOSE: To compare latanoprost with the fixed-combination latanoprost-timolol in
      glaucoma or ocular hypertension patients switched from a combination glaucoma
      therapy with timolol and another nonprostaglandin medication. DESIGN: Prospective
      randomized clinical trial. METHODS: Glaucoma or ocular hypertension patients
      receiving a combined treatment of timolol 0.5% and another nonprostaglandin
      medication (pilocarpine 4%, alpha-agonist, or a topical carbonic anhydrase
      inhibitor) underwent a 30-day washout of their medications. A masked observer
      then measured their intraocular pressure (IOP). The subjects were randomized to
      either latanoprost or fixed-combination latanoprost-timolol eyedrops to use once
      daily at 7 am. The IOP was measured again 30 days after the patients started
      using one of the study drugs by the same examiner at the same time. MAIN OUTCOME
      MEASURE: Comparison of the study medications' hypotensive effect. RESULTS: Fifty
      three eyes (28 in the latanoprost group and 25 in the latanoprost-timolol group)
      from 28 patients were included in the study. The IOP reduction was greater in
      both study groups compared with the previous combination therapy with timolol and
      another nonprostaglandin medication in millimeters of mercury (7.7+/-2.3 vs.
      5.5+/-2.3, P<0.001, for the latanoprost group; 8.5+/-3.5 vs. 6.3+/-2.7, P<0.001,
      for the latanoprost-timolol group) and percentage (35.8+/-8.2% vs. 25.6+/-8.9%,
      P<0.001, for the latanoprost group; 38.6+/-8.7% vs. 28.6+/-9.0%, P<0.001, for the
      latanoprost-timolol group). There was no statistical difference between
      latanoprost and fixed-combination latanoprost-timolol in reducing IOP, in either
      millimeters of mercury (P = 0.3) or percentage (P = 0.2). CONCLUSIONS: Both
      latanoprost and fixed-combination latanoprost-timolol may be viable substitutes
      for timolol and another nonprostaglandin medication in glaucoma or ocular
      hypertension patients.

PMID- 16458965
TI  - Clinical features of Chinese patients with Fuchs' syndrome.
AB  - PURPOSE: To characterize the clinical features of Chinese patients with Fuchs'
      syndrome. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One
      hundred eighteen eyes of 104 consecutive patients with Fuchs' syndrome initially
      examined between January 1999 and March 2005. METHODS: The history and clinical
      findings of all consecutive Fuchs' patients attending the Zhongshan Ophthalmic
      Center were reviewed. Auxiliary examinations, including laser flare-cell
      photometry, ultrasound biomicroscopy (UBM), fundus fluorescein angiography (FFA),
      and serologic tests for Toxoplasma gondii, were performed in certain cases. MAIN
      OUTCOME MEASURES: Patients' demographics, clinical presentation, and auxiliary
      examination findings. RESULTS: One hundred four patients (49 male, 55 female)
      were included in this study. Unilateral involvement was noted in 90 patients
      (86.5%). The most common symptom was blurred or decreased vision (86%). Stellate
      and medium-sized keratic precipitates (KPs) were noted in 108 eyes (91.5%). A
      mild anterior chamber (AC) reaction was observed in all the affected eyes.
      Heterochromia was observed in only 15 affected eyes, although there were varying
      degrees of iris depigmentation in all patients. Iris nodules, mostly Koeppe, were
      present in 28.0% of the affected eyes. Complicated cataract, vitreous opacity,
      and secondary glaucoma were observed in 84 of 118 eyes (70.7%), 31 eyes of 42
      eyes (73.8%), and 24 of 118 eyes (23.1%), respectively. The mean laser flare
      photometry value (6.4+/-2.3 photon counts per millisecond) and the cell number in
      the AC (1.5+/-1.2 cells per 0.5 mm3) in 25 patients were both significantly
      higher than those in 25 healthy controls (5.3+/-2.3 photon counts per millisecond
      and 0.8+/-0.6 cells per 0.5 mm3) (P<0.05). Ultrasound biomicroscopy revealed
      exudates adjacent to the ciliary body in 18 of 24 patients (75%). Serological
      tests failed to confirm an association of Fuchs' syndrome with toxoplasmosis.
      Retinal capillary leakage in the midperipheral fundus and disc staining at the
      late stage were observed in most of the eyes examined by FFA. CONCLUSION: Fuchs'
      syndrome in Chinese patients is characterized by a mild uveitis with
      characteristic KPs, varying degrees of iris depigmentation, and, occasionally,
      heterochromia. Exudates adjacent to the ciliary body and subclinical retinal and
      optic nerve involvement were common in the patients who were studied by UBM and
      FFA.

PMID- 16458966
TI  - Orbital carcinoid metastases.
AB  - OBJECTIVE: To describe a series of patients with metastatic orbital carcinoid
      tumors. DESIGN: Retrospective case series and literature review. PARTICIPANTS AND
      METHODS: Patients were identified from the orbital database and pathology records
      at Moorfields Eye Hospital. Records were evaluated for age at presentation, race,
      gender, laterality, visual function and clinical features, site of orbital
      metastasis, treatment, and outcome. The site of the primary tumor, presence of
      systemic symptoms, diagnosis and treatment of the primary tumor, and current
      survival status were also noted. MAIN OUTCOME MEASURES: Time from tumor to death.
      RESULTS: Thirteen patients (9 male) had an average age at biopsy-proven diagnosis
      of 65.3 years. The primary tumor was ileal in 7, colonic in 4, and from bronchus
      and breast (1 each); in 9 patients, the primary tumor was already known. Eleven
      of the 13 patients had noted a mass, 8 had diplopia, 3 had reduced vision, and
      only 2 had orbital pain. One patient presented with visual hallucinations.
      Imaging showed single muscle enlargement in 7 patients, a discrete mass in 5, and
      diffuse fat infiltration in 1 patient. Six patients underwent a meta-iodobenzyl
      guanidine/octreotide scan and metastatic disease was found in 4. Four patients
      underwent exenteration, 5 had radiotherapy after tumor debulking, 2 had
      radiotherapy alone, and 2 patients had local radiotherapy with receptor-targeted
      chemotherapy. Seven patients died from metastatic tumor. Kaplan-Meier analysis
      showed a 5-year survival rate of 72% and a 10-year survival rate of 38%.
      Comparison of the current series with other published series shows a significant
      difference (improvement) in survival at 5 years (P = 0.027) but not at 10 years
      (P = 0.08). CONCLUSIONS: The largest published series of orbital carcinoid tumors
      is presented, there being a recent trend towards less aggressive surgical
      management and probably a greater survival rate.

PMID- 16458967
TI  - Patient-reported behavior and problems in using glaucoma medications.
AB  - OBJECTIVE: The objectives of the current study were to describe the different
      types of problems patients receiving adjunctive therapy reported having when
      taking their glaucoma medications and to examine the relationship between patient
      reported problems in taking their glaucoma medications and patient adherence.
      DESIGN: Cross-sectional survey. PARTICIPANTS: A survey was distributed to
      glaucoma patients in 4 geographically distinct ophthalmology practices. We
      excluded patients using only 1 glaucoma medication. The survey was completed by
      324 patients. METHODS: For each patient, average percent adherence to his or her
      glaucoma medication regimen was calculated. Logistic regression was used to
      examine how patient characteristics and problems in using glaucoma medications
      were related to reported adherence. MAIN OUTCOME MEASURE: Whether patients were
      less than 100% adherent in the previous week. RESULTS: We found that 60% of
      patients reported 1 or more problems with taking their glaucoma medications.
      Fourteen percent of patients reported being less than 100% adherent to their
      glaucoma regimen medications during the previous week. Patients who had
      difficulty remembering to take their glaucoma medications and those who reported
      that they had other problems or concerns with their glaucoma medications were
      significantly less likely to be 100% adherent. CONCLUSIONS: Patient adherence to
      a glaucoma medication regimen could be improved among patients receiving
      adjunctive therapy. Ophthalmologists and their clinical colleagues should make
      sure to discuss the problems and concerns that patients may have in taking their
      glaucoma medications in an effort to improve adherence.

PMID- 16458969
TI  - Associations between elevated intraocular pressure and glaucoma, use of glaucoma
      medications, and 5-year incident cataract: the Blue Mountains Eye Study.
AB  - PURPOSE: To examine incident relationships between elevated intraocular pressure
      (IOP), open-angle glaucoma (OAG), and use of glaucoma medications with 5-year
      incident cataract. DESIGN: Population-based cohort study. PARTICIPANTS: The
      Australian Blue Mountains Eye Study examined 3654 participants > or =50 years old
      at baseline (82.4% response; 1992-1994); 2335 eligible participants were
      reexamined after 5 years (75.1% response; 1997-1999). METHODS: A detailed medical
      and ocular history, including current medications, was taken, and a comprehensive
      eye examination, including applanation tonometry, automated perimetry, and lens
      photography, was performed at each examination. The Wisconsin system was used to
      grade lens photographs in assessing incident nuclear, cortical, and posterior
      subcapsular cataract (PSC). Data from both eyes were assessed using generalized
      estimating equation analyses. MAIN OUTCOME MEASURES: Elevated IOP was defined as
      > or =21 mmHg. Open-angle glaucoma was diagnosed from typical glaucomatous field
      loss with matching optic disc cupping, without reference to IOP. Subjects without
      OAG or secondary or angle-closure glaucoma with IOP > 21 mmHg in either eye were
      classified as having ocular hypertension (OH), as were non-OAG subjects with IOP
      < 22 mmHg using glaucoma medications. Wisconsin levels 4 to 5 were graded as
      nuclear cataract, at least 5% lens involvement was graded as cortical cataract,
      and any PSC defined its presence. RESULTS: The 5-year incidence of nuclear
      cataract was 23.4% (592/2532), or 23.1% (574/2486) after excluding subjects using
      glaucoma medication. A marginally significant association was found for elevated
      IOP or OH at baseline and incident nuclear cataract (odds ratio [OR], 1.93 [95%
      confidence interval (CI), 0.97-3.89], and OR, 1.83 [95% CI, 0.96-3.48],
      respectively) in subjects not using glaucoma medications, after multivariate
      adjustment. Age- and gender-adjusted analyses showed similar but statistically
      significant associations. The association between elevated IOP or OH and nuclear
      cataract was significant in multivariate analyses (OR, 2.07 [95% CI, 1.04-3.12],
      and OR, 1.78 [95% CI, 1.05-3.01], respectively). Use of glaucoma medications was
      associated with nonsignificantly increased adjusted odds for incident nuclear
      cataract (OR, 1.90 [95% CI, 0.92-3.92]). No associations, however, were found
      with incident cortical cataract or PSC. CONCLUSIONS: Elevated IOP may increase
      the risk of nuclear cataract, but not that of other types. The use of glaucoma
      medications could magnify this risk.

PMID- 16458968
TI  - Intravitreal bevacizumab (Avastin) for neovascular age-related macular
      degeneration.
AB  - PURPOSE: To report the short-term safety, biologic effect, and a possible
      mechanism of action of intravitreal bevacizumab in patients with neovascular age
      related macular degeneration (AMD). DESIGN: Interventional, consecutive,
      retrospective case series. PARTICIPANTS: Eighty-one eyes of 79 patients with
      subfoveal neovascular AMD. METHODS: Patients received intravitreal bevacizumab
      (1.25 mg) on a monthly basis until macular edema, subretinal fluid (SRF), and/or
      pigment epithelial detachment (PED) resolved. Ophthalmic evaluations included
      nonstandardized Snellen visual acuity (VA), complete ophthalmic examination,
      fluorescein angiography, and optical coherence tomography (OCT). MAIN OUTCOME
      MEASURES: Assessments of safety, changes in Snellen VA, OCT retinal thickness,
      and angiographic lesion characteristics were performed. RESULTS: No significant
      ocular or systemic side effects were observed. Most patients (55%) had a
      reduction of >10% of baseline retinal thickness at 1 week after the injection. At
      4 weeks after injection, 30 of 81 eyes demonstrated complete resolution of
      retinal edema, SRF, and PEDs. Of the 51 eyes with 8 weeks' follow-up, 25 had
      complete resolution of retinal thickening, SRF, and PEDs. At 1, 4, 8,and 12
      weeks, the mean retinal thickness of the central 1 mm was decreased by 61, 92,
      89, and 67 mum, respectively (P<0.0001 for 1, 4, and 8 weeks and P<0.01 for 12
      weeks). At 4 and 8 weeks, mean VA improved from 20/200 to 20/125 (P<0.0001).
      Median vision improved from 20/200 to 20/80(-) at 4 weeks and from 20/200 to
      20/80 at 8 weeks. CONCLUSIONS: Short-term results suggest that intravitreal
      bevacizumab (1.25 mg) is well tolerated and associated with improvement in VA,
      decreased retinal thickness by OCT, and reduction in angiographic leakage in most
      patients, the majority of whom had previous treatment with photodynamic therapy
      and/or pegaptanib. Further evaluation of intravitreal bevacizumab for the
      treatment of choroidal neovascularization is warranted.

PMID- 16458970
TI  - Posterior sub-Tenon's capsule injection of triamcinolone acetonide prevents
      panretinal photocoagulation-induced visual dysfunction in patients with severe
      diabetic retinopathy and good vision.
AB  - PURPOSE: To evaluate prospectively the efficacy of a single sub-Tenon's capsule
      injection of triamcinolone acetonide (TA) against panretinal photocoagulation
      (PRP)-induced macular thickening and visual disturbance in patients with severe
      diabetic retinopathy and good vision. DESIGN: Prospective, comparative,
      interventional case series. PARTICIPANTS: Twenty eyes of 10 patients with severe
      nonproliferative diabetic retinopathy or non-high-risk proliferative diabetic
      retinopathy whose visual acuity was 20/40 or better (<0.3 in logarithm of the
      minimum angle of resolution [logMAR] acuity) before the PRP, whose retinopathy
      was bilateral and symmetrical. The averaged parafoveal retinal thickness was more
      than 300 microm, leading to a worse visual prognosis after PRP. INTERVENTION: Sub
      Tenon's capsule injection of 20 mg TA. MAIN OUTCOME MEASURES: Best-corrected
      visual acuity (BCVA) with logMAR chart and averaged foveal thickness (FT) using
      the retinal mapping program of optical coherence tomography. METHODS: In all
      patients, PRP was performed every other week for 4 sessions on both eyes, and 1
      week before PRP; 1 eye received the TA injection, and the other eye served as a
      control. The clinical course of BCVA and FT was monitored for up to 24 weeks
      after beginning PRP. RESULTS: Before TA injection, BCVA and FT were 0.055+/-0.072
      and 235.5+/-37.5 microm in the TA-injected eye and 0.065+/-0.071 and 233.7+/-39.8
      microm in the control eye, respectively; there was no significant difference
      between eyes. After the TA injection, FT in the TA-injected eyes was
      significantly decreased. During and after the PRP, FT in the control eye
      increased dramatically and reached 312.0+/-68.2 microm at 24 weeks, which was
      significantly different from that in the TA-injected eyes (235.3+/-38.6 microm at
      24 weeks). Best-corrected visual acuity in the control eye decreased with time to
      0.24+/-0.13; in contrast, and BCVA in the TA-injected eye was good (to 0.085+/
      0.11) . CONCLUSIONS: As a pretreatment for PRP, a single sub-Tenon's capsule
      injection of TA has beneficial effects for preventing PRP-induced foveal
      thickening and visual dysfunction in patients with severe diabetic retinopathy
      and good vision.

PMID- 16458972
TI  - Aluminum in hippocampal neurons from humans with Alzheimer's disease.
AB  - Using a staining technique developed in 2004, we examined hippocampal tissue from
      autopsy-confirmed cases of Alzheimer's disease (AD) and controls. The stain
      disclosed aluminum in cells and subcellular structure. All pyramidal neurons in
      these aged specimens appeared to exhibit at least some degree of aluminum
      staining. Many displayed visible aluminum only in their nucleolus. At the other
      extreme were neurons that stained for aluminum throughout their nucleus and
      cytoplasm. The remainder exhibited intermediate degrees of staining. On the basis
      of their aluminum staining patterns, all pyramidal neurons could be classified
      into stages that indicated two distinct neuropathological processes, either (1)
      progressive increase of nuclear aluminum (often accompanied by granulovacuolar
      degeneration with granules that stain for aluminum) or (2) formation of
      neurofibrillary tangles (NFTs) in regions of aluminum-rich cytoplasm, especially
      in AD brain tissue. In the latter process, intraneuronal NFTs appeared to
      displace nuclei and then enucleate the affected neurons during the course of
      their transformation into extracellular NFTs. Given that the NFTs we observed in
      human neurons always developed in conjunction with cytoplasmic aluminum, we
      hypothesize that aluminum plays an important role in their formation and should
      therefore be reconsidered as a causative factor for AD.

PMID- 16458971
TI  - Structured journal club as a tool to teach and assess resident competence in
      practice-based learning and improvement.
AB  - PURPOSE: To describe the use of the journal club as a tool to teach and assess
      competency in practice-based learning (PBL) and improvement among residents in
      ophthalmology. DESIGN: Interventional case series. PARTICIPANTS: Ophthalmology
      residents. SETTING: Three academic ophthalmology residency programs in the United
      States. METHODS: A survey was performed of self-assessed skills in PBL among
      residents in ophthalmology training before and after the implementation of a
      structured review checklist during a traditional resident journal club. The
      survey had 5 domains, including (A) appraise and assimilate evidence, (B) read a
      journal article critically, (C) use a systematic and standardized checklist, (D)
      apply knowledge of study designs and statistical methods, and (E) maintain a self
      documented written record of compliance. The respondents scored their ability
      (range, 1-5). RESULTS: The use of a structured journal club tool was associated
      with a statistically significant improvement in self-assessed ability in all 5
      domains. CONCLUSIONS: Although validity, reliability, and long-term efficacy
      studies are necessary, the structured journal club is one method of teaching and
      assessing resident competency in PBL and improvement.

PMID- 16458973
TI  - What has been learnt from study of dopamine receptors in Parkinson's disease?
AB  - Since the introduction of dopamine replacement therapy using L-3,4
      dihydroxyphenyalanine (L-DOPA) to treat Parkinson's disease and the recognition
      of the problems associated with L-DOPA use, numerous studies have investigated
      dopamine receptor regulation and function in Parkinson's disease. These studies
      have provided insight into the pathological process of the disorder and the
      molecular consequences of chronic dopaminergic treatment, but they have been less
      successful in identifying new pharmacological targets or treatment regimes that
      are as effective as L-DOPA at alleviating the symptoms of Parkinson's disease.
      This review will present a summary of the reported changes in dopamine receptor
      regulation and function that occur in Parkinson's disease and will discuss their
      contribution to the current pharmacological management of Parkinson's disease.

PMID- 16458975
TI  - Ten rules of academic life: reflections on the career of an affective disorders
      researcher.

PMID- 16458974
TI  - Mental effect of cholesterol in males: protective effect?
AB  - BACKGROUND: While the benefits of low cholesterol for physical health are not in
      doubt, a potential negative aspect of low cholesterol for mental health is
      suggested by several studies. To examine the association between cholesterol and
      mental health, the authors performed an observational study. METHOD: From April
      1995 to March 2002, a series of questionnaires pertaining to physical activity,
      food consumption, alcohol, coffee, smoking, and mental health (12 item-version of
      General Health Questionnaire: GHQ-12) were administered to 1972 employees in
      Japan. Subjects with less than 150 mg/dL of total cholesterol (very low
      cholesterol cohort) and other subjects (control cohort) were followed up for one
      to six years, and their mental health compared using GHQ caseness (GHQ-12 scores
      more than 3). RESULTS: Kaplan-Meier survival curves revealed that the very low
      cholesterol cohort had significantly greater GHQ caseness than the control
      cohort. Notably, this finding applied to males but not to females. After
      adjustment for general health, Cox's proportional hazards regression model
      confirmed this association in males only. The survival curves of control cohort
      were significantly different between males and females whereas those of very low
      cholesterol cohort were not. LIMITATIONS: GHQ caseness was regarded as "death" in
      the survival analysis. As such, it is not possible to differentiate between
      transient and persistent mental dysfunction and therefore may lead to
      overestimation of GHQ caseness over observational years. CONCLUSION: The present
      findings suggest that very low cholesterol may be associated with worse mental
      health in males and conversely and interestingly indicate that moderate (but not
      very low) cholesterol levels may protect mental health in males.

PMID- 16458976
TI  - Effectiveness and cost-effectiveness of antidepressant treatment in primary
      health care: a six-month randomised study comparing fluoxetine to imipramine.
AB  - BACKGROUND: Over the past decade, studies of the effectiveness of pharmacological
      treatment for depression have often been based on research designs intended to
      measure efficacy, and for this reason the results are of limited
      generalizability. Research is needed comparing the clinical and economic outcomes
      of antidepressants in day-to-day clinical practice. METHODS: A six-month
      randomised prospective naturalistic study comparing fluoxetine to imipramine
      carried out in three primary care health centres. Outcome measures were the
      Montgomery Asberg Depression Rating Scale (MADRS), direct costs, indirect costs
      and total costs. Subjects were evaluated at the beginning of treatment and at
      one, three and six months thereafter. RESULTS: Of the 103 patients, 38.8% (n =
      40) were diagnosed with major depressive disorder, 14.6% (n = 15) with dysthymic
      disorder, and 46.6% (n = 48) with depressive disorder not otherwise specified.
      Patients with major depressive disorder or dysthymic disorder achieved similar
      clinical improvement in both treatment groups (mean MADRS ratings decrease in
      major depressive disorder from baseline to 6 months of 18.3 for imipramine and
      18.8 for fluoxetine). For patients with major depressive disorder and dysthymic
      disorder, the imipramine group had fewer treatment-associated costs (imipramine
      469.66 Euro versus fluoxetine 1,585.93 Euro in major depressive disorder, p <
      0.05; imipramine 175.39 Euro versus fluoxetine 2,929.36 Euro in dysthymic
      disorder, p < 0.05). The group with depressive disorder not otherwise specified
      did not experience statistically significant differences in clinical and costs
      outcomes between treatment groups. LIMITATIONS: Exclusion criteria, participating
      physicians may not represent GPs. CONCLUSIONS: In a primary care context,
      imipramine may represent a more cost-effective treatment option than fluoxetine
      for treating major depressive disorder or dysthymic disorder. There were no
      differences in cost-effectiveness in the treatment of depressive disorder not
      otherwise specified.

PMID- 16458977
TI  - Concern about tall stature during adolescence and depression in later life.
AB  - OBJECTIVE: This retrospective cohort study aimed to examine the long-term
      psychosocial outcomes for women assessed or treated during adolescence for tall
      stature. METHOD: Women assessed or treated for tall stature identified from the
      records of Australian paediatricians were eligible to participate. Psychosocial
      outcomes were measured using the depression, mania and eating disorders modules
      of the Composite International Diagnostic Interview (CIDI), the SF-36, and an
      index of social support. RESULTS: There was no significant difference between
      treated and untreated women in the prevalence of 12 month or lifetime major
      depression, eating disorders, scores on the SF-36 mental health summary scale, or
      the index of social support. However, compared with the findings of population
      based studies, the prevalence of major depression in both treated and untreated
      tall girls was high (12 month prevalence: untreated 10.7%, treated 11.2%;
      lifetime prevalence: untreated 29.4%, treated 26.6%). Factors significantly
      associated with lifetime major depression in this study were self-reported
      difficulties during adolescence being the reason for seeking a medical assessment
      of height (OR 2.25, 95% CI 1.4-3.6) and a negative experience of the assessment
      or treatment procedures (OR 2.04, 95% CI 1.4-3.0). CONCLUSION: Long-term follow
      up of a large cohort of tall girls showed that psychological outcomes among both
      treated and untreated women were poor and that the intended psychosocial benefit
      of treatment may not have been realized. The findings highlight the importance of
      attending to the mental health of adolescents presenting for management of
      conditions where self-concept and body image are a primary focus.

PMID- 16458978
TI  - Treatment of bereavement-related depression and traumatic grief.
AB  - In the bereaved, approximately 40% meet criteria for major depression within a
      month of the death. At a year, approximately 15% of the bereaved are depressed
      and at 2 years, the figure is approximately 7%. Open-label trials of medication
      for bereavement-related depression have shown promising results for desipramine,
      nortriptyline, and bupropion SR. One double-blind controlled trial supports the
      use of nortriptyline, but interpersonal psychotherapy did no better than placebo.
      In all these trials, depressive symptoms improve more than bereavement symptoms.
      Effective open-label treatments for traumatic grief include paroxetine,
      nortriptyline, and a form of psychotherapy called traumatic grief treatment.

PMID- 16458979
TI  - Interleukin-6 and IL-6 receptor cell expression in testis of rats with autoimmune
      orchitis.
AB  - Experimental autoimmune orchitis (EAO) is an organ-specific model of autoimmunity
      characterized by an interstitial lymphomononuclear cell infiltrate as well as
      sloughing and apoptosis of germ cells. EAO was induced in adult male Sprague
      Dawley rats by active immunization with testicular homogenate and adjuvants. Rats
      injected with saline solution and adjuvants were used as control group. The aim
      of this work was to study the expression of interleukin-6 (IL-6) and its receptor
      (IL-6R) in the testis of rats with EAO and analyze whether IL-6 could be involved
      in germ cell apoptosis. By immunohistochemistry, we detected IL-6 expression in
      testicular macrophages and Leydig cells of control and EAO rats. Sertoli cells
      showed IL-6 immunoreactivity in most of the seminiferous tubules of control rats,
      while a few IL-6+ Sertoli cells were found in the testis of rats with EAO. IL-6R
      immunoreactivity was observed in macrophages, Leydig and germ cells. A
      significant increase was noted in the number of IL-6R+ germ cells in rats with
      EAO compared to control rats. The content of IL-6 (ELISA) in the conditioned
      media obtained from testicular macrophages of rats with orchitis was
      significantly higher than in the control group. By immunofluorescence performed
      on isolated testicular macrophages, IL-6 was shown to be expressed by monocytes
      recently arrived from circulation (ED1+ cells), while resident macrophages (ED2+
      cells) were negative. In vitro experiments (trypan blue and MTS assays) showed
      that IL-6 (50 ng/ml) reduced germ cell viability. We demonstrated also using the
      TUNEL technique that IL-6 added to cultures of seminiferous tubule segments
      induced apoptosis of germ cells. Our results suggest that IL-6 and IL-6R may be
      involved in the pathogenesis of autoimmune orchitis by promoting testicular
      inflammation and germ cell apoptosis.

PMID- 16458980
TI  - A brief history of British Pharmacological Society meetings.
AB  - The British Pharmacological Society (BPS) is currently celebrating its 75th
      anniversary. It is therefore a young society compared with some other biomedical
      societies and particularly when compared with the origins of the oldest learned
      societies. In this article, I briefly review the origins of learned societies and
      examine the rise of pharmacology in the UK, as reflected in the scientific
      meetings of the BPS. The rapid growth of British pharmacology and clinical
      pharmacology in the 1970s and 1980s and changes in the way that scientific
      literature is published have resulted in the BPS having to adapt quickly in the
      way that its meetings are run. However, evidence suggests that the Society will
      continue to move strongly and confidently towards its 100th birthday.

PMID- 16458982
TI  - Aldosterone increases RAMP1 expression in mesenteric arteries from spontaneously
      hypertensive rats.
AB  - OBJECTIVE: We analysed the effect of aldosterone on calcitonin gene-related
      peptide (CGRP) mediated vasodilation in noradrenaline precontracted endothelium
      denuded mesenteric arteries segments from Wistar Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR) and the effect of aldosterone on calcitonin
      receptor-like receptor (CL receptor) and receptor activity modifying protein 1
      (RAMP1) expression in endothelium-denuded mesenteric arteries from SHR rats.
      RESULTS: CGRP 0.1 nM-0.1 microM induced a concentration-dependent relaxation that
      was enhanced by aldosterone 1 microM in SHR only. Incubation with RU 486 10
      microM significantly reduced the enhancement of CGRP-relaxation produced by
      aldosterone in SHR. CL receptor expression was not modified in either strain,
      while RAMP1 expression was enhanced in SHR by aldosterone 1 microM 120 min and
      0.1 microM 120 min. This up-regulation of RAMP1 was prevented by RU 486 10
      microM. CONCLUSIONS: Aldosterone, through glucocorticoid receptor activation,
      increases the vasodilatory effect of CGRP in SHR mesenteric arteries, which seems
      to be mediated by increased RAMP1 expression.

PMID- 16458981
TI  - Effects of benzo(a)pyrene exposure on killifish (Fundulus heteroclitus) aromatase
      activities and mRNA.
AB  - Cytochrome P450 aromatase (CYP19) plays an important role in steroid homoeostasis
      by converting androgens to estrogens. To evaluate the effects of benzo(a)pyrene
      (BaP), a model carcinogenic PAH and AhR ligand, on aromatase mRNA expression and
      enzyme activity, adult Fundulus were exposed to water-borne BaP (1 and 10
      microg/L) for 15 days, and embryos were exposed to 10 microg/L for 10 days.
      Effects of BaP were examined by tissue, gender, and season in adults.
      Constitutively, the sexes did not have significantly different CYP19A2 mRNA
      levels, however females had higher brain aromatase activity. Female control
      killifish had more than 700-fold more CYP19A1 mRNA in their gonads compared to
      males. Within brain tissue of both sexes, there was 100-fold more CYP19A2 mRNA
      compared to CYP19A1. In ovary, CYP19A1 predominated by approximately 30-fold over
      the CYP19A2, but in testis there was relatively more CYP19A2. In embryos there
      was approximately 5-fold higher CYP19A2 expression. Due to high inter-individual
      variability, a significant effect of BaP treatment by gender, season or age was
      not observed for either aromatase mRNA. However, ovarian aromatase activity was
      significantly decreased by 10 microg/L BaP, while female brain activity was
      increased following winter exposure. These findings suggest that the aromatase
      enzyme is a potential target for disruption of fish developmental and
      reproductive physiology by BaP.

PMID- 16458983
TI  - A stable, inducible, dose-responsive ODC overexpression system in human cell
      lines.
AB  - ODC is a labile protein subject to rapid turnover, and a conditional expression
      system providing long-term overexpression may be helpful in further understanding
      the biochemical properties of this enzyme and elucidating aspects of the
      polyamine biosynthetic pathway that have otherwise been difficult to study.
      HEK293 and LNCaP cell lines were engineered to stably and inducibly overexpress
      ODC using a Tet-on inducible construct. Clones from both cell lines were
      characterized by evaluating ODC mRNA expression, ODC activity, intracellular and
      extracellular polyamine levels, SSAT activity and growth kinetics. The ODC
      inducible cell lines were time- and dose-responsive providing a mechanism to
      increase ODC and putrescine accumulation to a desired level in a flexible and
      controllable manner. The findings demonstrate that LNCaP ODC overexpressing cells
      maintained over a 100-fold increase in ODC activity and over a 10-fold increase
      in intracellular putrescine after 6 h. ODC induction at the highest levels was
      accompanied by a slight decline in intracellular spermidine and spermine levels
      and this observation was supported by the finding that SSAT activity was induced
      over 40-fold under these conditions. Growth rate remained unaffected following at
      least 12 h of ODC overexpression. Similar results were observed in the HEK293 ODC
      overexpressing cells.

PMID- 16458984
TI  - The effect of moderate exercise training on skeletal muscle myosin heavy chain
      distribution in chronic heart failure.
AB  - BACKGROUND: The myosin heavy chain (MHC) is altered in chronic heart failure
      (CHF), but the effect of exercise on MHC expression in CHF patients is not
      understood. The aim of the present study was to show the effect of aerobic
      exercise on MHC distribution in patients with CHF. METHODS: Patients (n=17) with
      stable NYHA class I-III CHF were randomised into training and control groups. For
      a period of three months, the training group cycled on an ergometric cycle 3
      times a week for 30 min, the control group continued as they did previously. Both
      a baseline and a final 3 month graded maximal exercise test and exercise
      endurance test with constant submaximal work load were performed. Muscle samples,
      obtained from vastus lateralis muscle at baseline and after 3 months from the 8
      patients in the training group and the 9 in the control group, were analysed for
      MHC distribution using SDS-polyacrylamide gel electrophoresis. RESULTS: Baseline
      MHC distributions were similar in both groups and training did not alter the MHC
      distribution. Exercise duration, at constant submaximal work load, improved from
      14.9+/-7.1 to 26.9+/-9.6 min (p<0.01 for the change between the groups). Training
      did not improve peak oxygen consumption. CONCLUSION: No correlation between the
      change in exercise capacity and MHC distribution appeared despite the significant
      improvement of exercise duration.

PMID- 16458985
TI  - A simple 1+ dimensional model of rowing mimics observed forces and motions.
AB  - We have devised a simple, yet predictive model of the mechanics of both sculling
      and sweep rowing that reasonably mimics observed kinematic and force data. Our
      physical model is largely based upon the model proposed by Alexander [Alexander,
      F. H. (1925). The theory of rowing. In Proceedings of the University of Durham
      Philosophical Society (pp. 160-179).]. The model's primary features include: one
      dimensional momentum balance, a point mass rower, infinitely stiff oars with
      inertia and non-infinitesimal stroke angles, and quadratic relationships between
      force and velocity for the boat and oar blade. Using an inverse dynamics
      approach, we are able to construct reasonable fits to force and kinematic data of
      real rowing. We show that the model is able to reasonably well predict boat
      velocity even when we do not fit for it. A sensitivity analysis shows that the
      quality of fit is more sensitive to the boat and oar drag coefficients than to
      other physical parameters. Allowing oar slip (C(D) < infinity) proves to be a
      necessary model ingredient but, for example, allowing for oar flexibility does
      not improve the quality of fit. The model seems to have the key terms and a
      minimum of superfluous terms for investigations of rowing.

PMID- 16458986
TI  - Studies on the activity of a bidirectional promoter of Mungbean yellow mosaic
      India virus by agroinfiltration.
AB  - The AV promoter expressing AV1 and AV2 genes and AC1 promoter expressing AC1 gene
      are present in opposite orientation in the intergenic region of Mungbean yellow
      mosaic India virus (MYMIV). Transient Agrobacterium-mediated delivery of putative
      promoter constructs into Nicotiana benthamiana and different legumes, followed by
      reporter gene (beta-d-glucuronidase, GUS) assay, identified the promoter region
      of both AC1 and AV genes that is necessary for transcriptional initiation.
      Transcription activator protein-independent activity of AV promoter and
      differential regulation of AC1 promoter are unique to MYMIV. The AV promoter is a
      composite core promoter having both TATA box and Initiator elements
      (TATA(+)Inr(+)). Many transcription factor binding sites were identified in the
      upstream promoter sequences of both virion and complementary sense genes, which
      might be used in the transcription regulation studies of the host plant as well
      as the virus.

PMID- 16458987
TI  - Silk fibroin as an organic polymer for controlled drug delivery.
AB  - The pharmaceutical utility of silk fibroin (SF) materials for drug delivery was
      investigated. SF films were prepared from aqueous solutions of the fibroin
      protein polymer and crystallinity was induced and controlled by methanol
      treatment. Dextrans of different molecular weights, as well as proteins, were
      physically entrapped into the drug delivery device during processing into films.
      Drug release kinetics were evaluated as a function of dextran molecular weight,
      and film crystallinity. Treatment with methanol resulted in an increase in beta
      sheet structure, an increase in crystallinity and an increase in film surface
      hydrophobicity determined by FTIR, X-ray and contact angle techniques,
      respectively. The increase in crystallinity resulted in the sustained release of
      dextrans of molecular weights ranging from 4 to 40 kDa, whereas for less
      crystalline films sustained release was confined to the 40 kDa dextran. Protein
      release from the films was studied with horseradish peroxidase (HRP) and lysozyme
      (Lys) as model compounds. Enzyme release from the less crystalline films resulted
      in a biphasic release pattern, characterized by an initial release within the
      first 36 h, followed by a lag phase and continuous release between days 3 and 11.
      No initial burst was observed for films with higher crystallinity and subsequent
      release patterns followed linear kinetics for HRP, or no substantial release for
      Lys. In conclusion, SF is an interesting polymer for drug delivery of
      polysaccharides and bioactive proteins due to the controllable level of
      crystallinity and the ability to process the biomaterial in biocompatible fashion
      under ambient conditions to avoid damage to labile compounds to be delivered.

PMID- 16458988
TI  - Hydrophobically modified glycol chitosan nanoparticles as carriers for
      paclitaxel.
AB  - Self-assembled nanoparticles based on hydrophobically modified glycol chitosan
      (HGC) were prepared as a carrier for paclitaxel. HGC conjugates were prepared by
      chemically linking 5beta-cholanic acid to glycol chitosan chains using 1-ethyl-3
      (3-dimethylaminopropyl)-carbodiimide chemistry. In phosphate-buffered saline
      (PBS; pH 7.4), the synthesized HGC conjugates formed nano-sized particles with a
      diameter of 200 nm and exhibited high thermodynamic stability as reflected by
      their low critical aggregation concentration (0.03 mg/ml). Paclitaxel was
      efficiently loaded into HGC nanoparticles up to 10 wt.% using a dialysis method.
      The paclitaxel-loaded HGC (PTX-HGC) nanoparticles were 400 nm in diameter and
      were stable in PBS for 10 days. These PTX-HGC nanoparticles also showed sustained
      release of the incorporated of paclitaxel (80% of the loaded dose was released in
      8 days at 37 degrees C in PBS). Owing to sustained release, the PTX-HGC
      nanoparticles were less cytotoxic to B16F10 melanoma cells than free paclitaxel
      formulated in Cremophor EL. Injection of PTX-HGC nanoparticles into the tail vein
      of tumor-bearing mice prevented increases in tumor volume for 8 days. Finally,
      PTX was less toxic to the tumor-bearing mice when formulated in HGC nanoparticles
      than when formulated with Cremophor EL.

PMID- 16458989
TI  - Predictors of hyperglycaemic crises and their associated mortality in Jamaica.
AB  - The objective of the study was to determine the clinical characteristics and
      mortality of patients with hyperglycaemic hyperosmolar syndrome (HHS) and
      diabetic ketoacidosis (DKA) at a Jamaican tertiary care hospital. In a
      retrospective study of 1560 admissions for diabetes during the period 1998-2002,
      980 dockets were reviewed and 164 individuals met the ADA diagnostic criteria for
      DKA or HHS. Patients with HHS were older than DKA patients (64.5 years [95% CI:
      60.7-68.4] versus 35.9 years [95% CI: 30.2-41.6]), but were not more likely to be
      non-compliant with medications, infected, or male. Overall, 24% had a mixed
      DKA/HHS syndrome. Most DKA patients had type 2 diabetes (62%). Only 2% of HHS and
      6% of DKA/HHS patients had type 1 diabetes. Syndrome specific mortality was: DKA
      6.7%, HHS 20.3%, and DKA/HHS 25% (p for trend=0.013). Mortality increased
      significantly with age, especially in patients > or =50 years. Significant
      univariate predictors of mortality were altered mental status on admission, co
      existing medical disease, increasing age, older age at onset of diabetes, acute
      stressors, and DKA/HHS. In multivariate models, only altered mental status was
      significant (OR=3.59; 95% CI: 1.24-10.41). Hence, hyperglycaemic crises in a
      Jamaican tertiary care hospital are associated with significant mortality
      especially in patients who are older or with altered mental status.

PMID- 16458991
TI  - Hepatic stellate cells do not derive from the neural crest.
AB  - BACKGROUND/AIMS: Hepatic stellate cells (HSC) have been hypothesised to derive
      from the neural crest, based on their expression of multiple
      neural/neuroendocrine features and their contacts with autonomic nerve endings.
      METHODS: We studied the emergence of HSC in the liver during embryonic
      development in a transgenic mouse line expressing yellow fluorescent protein
      (YFP) in all neural crest cells and their derivatives. Cellular YFP expression in
      these mice was compared with desmin expression between embryonic day (E) 11.5 and
      adulthood. RESULTS: YFP was abundantly expressed in neural crest cells
      delaminating from the neural tube and in all known neural crest-derived
      structures and cell populations. In particular, YFP expressing cells perfectly
      mimicked the spatial and temporal pattern of enteric nervous system development
      from neural crest cells migrating from the postotic region. Cells within the
      adrenal medulla were also YFP positive. Analysis of the liver showed that desmin
      expressing, stellate-shaped, perisinusoidally located HSC were evident from E11.5
      onwards. However, no detectable YFP expression was seen in the developing liver
      or in HSC, from E11.5 until adulthood. CONCLUSIONS: These findings suggest HSC do
      not descend from the neural crest, and therefore may derive from the septum
      transversum mesenchyme, from endoderm or from the mesothelial liver capsule.

PMID- 16458992
TI  - Heme oxygenase attenuates oxidative stress and inflammation, and increases VEGF
      expression in portal hypertensive rats.
AB  - BACKGROUND/AIMS: The pathophysiological significance of heme oxygenase-1 up
      regulation in portal hypertension is not completely understood. In this study, we
      determined the role of heme oxygenase-1 on oxidative stress, inflammation,
      angiogenesis, and splanchnic hemodynamics in rats with portal hypertension
      induced by partial portal vein ligation. METHODS: Rats were treated with the heme
      oxygenase inhibitor SnMP or vehicle for 7 days. Then, oxidative stress was
      quantified by superoxide anion production, and inflammatory response was assessed
      by immunofluorescence. Expression of angiogenesis mediators was determined by
      western blotting, and the extent of portosystemic collaterals by radioactive
      microspheres. Hemodynamic studies were performed by flowmetry. RESULTS: Oxidative
      stress was significantly increased in the mesentery of portal hypertensive rats,
      as compared with sham-operated controls. In portal hypertensive rats, chronic
      heme oxygenase inhibition (1) potentiated oxidative stress and inflammation, (2)
      significantly decreased VEGF expression, without modifying the extent of
      collaterals or the splanchnic neovascularization, and (3) significantly decreased
      superior mesenteric artery blood flow and portal pressure. CONCLUSIONS: This
      study demonstrates that heme oxygenase plays an important (beneficial) role
      attenuating oxidative stress and inflammation, but it also plays a detrimental
      role in stimulating VEGF production, and contributing to the development of
      hyperdynamic splanchnic circulation in rats with portal hypertension.

PMID- 16458990
TI  - Matrix metalloproteinase-9 contributes to brain extravasation and edema in
      fulminant hepatic failure mice.
AB  - BACKGROUND/AIMS: Fulminant hepatic failure (FHF) can be dreadful. When coma sets
      in, brain edema develops taking FHF into a lethal course. Mechanisms of brain
      extravasation leading to brain edema remain incompletely understood. Matrix
      metalloproteinase (MMP)-9 is implicated in various brain injuries. We
      hypothesized that MMP-9 contributes to brain edema in FHF. METHODS: MMP-9 and its
      proform were assayed using SDS-PAGE and in situ gelatin zymographies. Brain
      extravasation was assessed with Evans blue. Brain water was determined by
      specific gravity and astrocytic endfoot swelling by electron microscopy. FHF in
      mice was induced by azoxymethane. MMP inhibitor GM6001 and MMP-9 monoclonal
      antibody were used. RESULTS: Active MMP-9 was significantly increased at the
      onset of coma and brain extravasation in FHF mice. Blocking MMP-9 with either
      GM6001 or MMP-9 monoclonal antibody significantly attenuated brain extravasation,
      astrocytic endfoot swelling, and brain edema. Brains of FHF mice did not show MMP
      9 activity. In contrast, livers of these animals showed marked up-regulation of
      MMP-9 activity. CONCLUSIONS: Our findings suggest that MMP-9 contributes to the
      pathogenesis of brain extravasation and edema in FHF. The necrotic liver is the
      source of MMP-9 in FHF. Inhibition of MMP-9 may protect against the development
      of brain edema in FHF.

PMID- 16458993
TI  - Pyruvate ameliorates the defect in ureogenesis from ammonia in citrin-deficient
      mice.
AB  - BACKGROUND/AIMS: Mutations in SLC25A13, encoding the mitochondrial aspartate
      glutamate carrier citrin, cause adult-onset type II citrullinemia (CTLN2) in
      humans. We have previously reported that although citrin-knockout (Ctrn-/-) mice
      fail to display symptoms of CTLN2, liver perfusion revealed a deficit in
      ureogenesis from ammonia accompanied by an increase in the perfusate lactate-to
      pyruvate (L/P) ratio. The present study explores the effects of pyruvate,
      aspartate and citrate on improving the abnormalities observed in the Ctrn-/-
      liver. METHODS: We measured the rate of ureogenesis from ammonium chloride using
      the liver-perfusion system. RESULTS: Pyruvate infusion lowered the L/P ratio and
      corrected the deficit in ureogenesis in the Ctrn-/- liver. This effect was found
      to be dose-dependent in both instances. Phenazine methosulfate, a cytosolic
      oxidant, also improved the rate of ureogenesis in the Ctrn-/- liver and led to a
      fall in the L/P ratio. The addition of aspartate or citrate did not change either
      the rate of ureogenesis or the L/P ratio in the Ctrn-/- liver. CONCLUSIONS:
      Citrin deficiency disturbs urea synthesis primarily as a result of an elevated
      cytosolic NADH/NAD+ ratio owing to limited reoxidation of reducing equivalents.
      Clinically, pyruvate may have a therapeutic benefit for CTLN2 patients.

PMID- 16458994
TI  - Potential role of trans-inhibition of the bile salt export pump by progesterone
      metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy.
AB  - BACKGROUND/AIMS: Progesterone metabolites such as 5alpha-pregnan-3alpha-ol-20-one
      (PM4) are elevated in serum of women with intrahepatic cholestasis of pregnancy
      (ICP). METHODS/RESULTS: When assayed in isolated perfused rat liver, PM4 did not
      induce cholestasis, whereas sulfated PM4 (PM4-S), which unlike PM4 is secreted
      into bile, reduced bile flow and bile acid (BA) output. Whether PM4-S inhibited
      the bile salt export pump (BSEP) was investigated. Radiolabeled methylesters (ME)
      of cholic acid and chenodeoxycholic acid were taken up by Xenopus laevis oocytes
      co-expressing rat BSEP and human carboxylesterase-1 (CES1), efficiently
      hydrolyzed to free BAs by CES1 and subsequently exported by BSEP. Rifampicin or
      cyclosporin A in the extracellular medium had no effect on BA efflux. In
      contrast, estradiol 17beta-D-glucuronide and several progesterone metabolites,
      including PM4-S, induced a marked non-competitive trans-inhibition of BSEP
      mediated BA efflux (Ki=20-60 microM). Mitochondrial activity was markedly
      impaired in oocytes incubated with BA-MEs, but not with free BAs. Co-expression
      of CES1 and BSEP partly protected oocytes from this toxic effect. Trans
      inhibition of BSEP abolished this protection. CONCLUSIONS: Several estrogens and
      progesterone metabolites are able to induce trans-inhibition of BSEP and the
      subsequent toxicity induced by the accumulation of BAs, which may play a role in
      the etiopathogenesis of ICP.

PMID- 16458995
TI  - Documenting domestication: the intersection of genetics and archaeology.
AB  - Domestication, a process of increasing mutual dependence between human societies
      and the plant and animal populations they target, has long been an area of
      interest in genetics and archaeology. Geneticists seek out markers of
      domestication in the genomes of domesticated species, both past and present day.
      Archaeologists examine the archaeological record for complementary markers-
      evidence of the human behavior patterns that cause the genetic changes associated
      with domestication, and the morphological changes in target species that result
      from them. In this article, we summarize the recent advances in genetics and
      archaeology in documenting plant and animal domestication, and highlight several
      promising areas where the complementary perspectives of both disciplines provide
      reciprocal illumination.

PMID- 16458996
TI  - Providing longitudinal health care information with the new German Health Card--a
      pilot system to track patient pathways.
AB  - The paper describes an application system that employs the new German Health Card
      to provide a technical solution for tracking patient pathways. The aim is to
      improve the flow and availability of health care information. We used standard
      software components and technologies in order to facilitate interoperability with
      multiple system platforms and allow for customizing as the specification process
      for the German Health Card is not yet completed. Every health care provider
      contact is recorded on the card and associated medical documents are stored in a
      central database and can be retrieved via Web Services running on a central
      application server. The patient pathway can thus be chronologically tracked by
      the clinician and relevant longitudinal information is made accessible quickly.
      Our system for tracking patient pathways with the new German Health Card can be
      regarded as a first example of its great future potential.

PMID- 16458997
TI  - Hypoxia-induced remodelling of PDE4 isoform expression and cAMP handling in human
      pulmonary artery smooth muscle cells.
AB  - Human pulmonary artery smooth muscle cells (hPASM cells) express PDE4A10,
      PDE4A11, PDE4B2, PDE4C and PDE4D5 isoforms. Hypoxia causes a transient up
      regulation of PDE4B2 that reaches a maximum after 7 days and sustained up
      regulation of PDE4A10/11 and PDE4D5 over 14 days in hypoxia. Seven days in
      hypoxia increases both intracellular cAMP levels, protein kinase A (PKA) activity
      and activated, phosphorylated extracellular signal regulated kinase (pERK) but
      does not alter either PKA isoform expression or total cAMP phosphodiesterase-4
      (PDE4) activity or cAMP phosphodiesterase-3 (PDE3) activity. Both the
      cyclooxygenase inhibitor, indomethacin and the ERK inhibitors, UO126 and PD980589
      reverse the hypoxia-induced increase in intracellular cAMP levels back to those
      seen in normoxic hPASM cells. Challenge of normoxic hPASM cells with
      prostaglandin E(2) (PGE(2)) elevates cAMP to levels comparable to those seen in
      hypoxic cells but fails to increase intracellular cAMP levels in hypoxic hPASM
      cells. The adenylyl cyclase activator, forskolin increases cAMP levels in both
      normoxic and hypoxic hPASM cells to comparable elevated levels. Challenge of
      hypoxic hPASM cells with indomethacin attenuates total PDE4 activity whilst
      challenge with UO126 increases total PDE4 activity. We propose that the hypoxia
      induced activation of ERK initiates a phospholipase A(2)/COX-driven autocrine
      effect whereupon PGE(2) is generated, causing the activation of adenylyl cyclase
      and increase in intracellular cAMP. Despite the hypoxia-induced increases in the
      expression of PDE4A10/11, PDE4B2 and PDE4D5 and activation of certain of these
      long PDE4 isoforms through PKA phosphorylation, we suggest that the failure to
      see any overall increase in PDE4 activity is due to ERK-mediated phosphorylation
      and inhibition of particular PDE4 long isoforms. Such hypoxia-induced increase in
      expression of PDE4 isoforms known to interact with certain signalling scaffold
      proteins may result in alterations in compartmentalised cAMP signalling. The
      hypoxia-induced increase in cAMP may represent a compensatory protective
      mechanism against hypoxia-induced mitogens such as endothelin-1 and serotonin.

PMID- 16458998
TI  - Peacock or Plum? Reflections on academic research career pathways.
AB  - PURPOSE OF THE PAPER: This paper critically deconstructs academic career pathways
      in research and explores possible future directions. BACKGROUND AND CONTEXT:
      Development in NHS policy and practice has brought about something of a sea
      change in academic career pathways in nursing and midwifery. Whilst once there
      was a fairly prescribed route into nurse education and then research,
      contemporary factors no longer foster such traditional routes. METHODS: In
      examining what a career pathway into academic nursing research may look like it
      may be useful first to delineate what are the basic assumptions that constitute
      'achievement' within such a career. Once pinpointed it is possible to map out
      different pathways that illustrate the diversity with which this has occurred.
      This provides a useful mirror for examining what may or may not be useful for the
      future. This paper explores three areas of the nurse academic career pathway:
      introspectively to understand where we are at the moment, retrospectively by
      examining composite research careers in order to gain insight for the final
      prospective section, where we make recommendations for the future. CONCLUSIONS:
      Nurses and midwives working in higher education require transparent and
      sustainable research strategies that facilitate clear research pathways in
      academia. The tensions between research and teaching are inevitable, but are
      manageable if workforce development uses individuals to their strengths and
      values diversity of contribution.

PMID- 16458999
TI  - Moral content and assignment marking: an exploratory study.
AB  - This small scale exploratory survey investigates the relation between the moral
      content of student assignments and potential marking behaviour by lecturers. A
      questionnaire containing a number of deliberately discriminatory statements was
      sent to a sample of nurse academics, and participants were asked to indicate
      whether the inclusion of these statements might affect the mark awarded. The
      sample was too small to undertake tests of statistical significance. However, the
      results tentatively suggest that a majority of participants would penalise
      assignments that contain morally questionable statements, and many would cite the
      code of professional conduct in justification. There appeared to be little
      difference in the response to statements that offered opinions (normative) or
      described actions (descriptive). However, differences between responses to
      statements discriminating against different groups were apparent, with racist
      statements being penalised more often and with greater severity than other
      categories. Qualitative data support the quantitative data. Several areas for
      discussion are identified, including the academic status of nursing, the use of
      the code of professional conduct, the moral claims made for nurses, a potential
      'hierarchy of wrongness', student self censorship, and inconsistency in marking.
      Further research is justified.

PMID- 16459000
TI  - Seroprevalence of Varicella-Zoster virus IgG antibodies in Swiss children during
      the first 16 months of age.
AB  - QUESTION UNDER STUDY: To investigate the persistence of maternal IgG antibodies
      against Varicella-Zoster virus (VZV) in infants and young children. METHODS:
      Serum specimens of children aged 0-16 months who had been hospitalized in our
      institution between 1994 and 1999 were identified from our routine serum
      collection. Exclusion criteria were: preterm delivery (<37 gestational weeks);
      suspected varicella infection or presence of exanthema of unknown etiology at
      time of serum collection; transfusion of blood products during 6 months preceding
      serum collection; foreign born mother; and previous VZV immunization. Serotesting
      for IgG antibodies against VZV was performed by use of a commercially available
      ELISA kit. RESULTS: Two hundred and fifty three serum specimens from 240 patients
      were analyzed. Age distribution of patients at time of specimen collection was: 0
      3 months: n=57; >3-6 months: n=47; >6-9 months: n=47; >9-12 months: n=48; >12-16
      months: n=54. Seroprevalence rates for IgG antibodies against VZV in the
      different age groups were 90% (0-3 months), 38% (>3-6 months); 0% (>6-9 and >9-12
      months); and 7% (>12-16 months). CONCLUSIONS: Our results demonstrate high levels
      of passively acquired humoral immunity against varicella in Swiss infants during
      the first 3 months of life. Beyond the first 3 months of life IgG antibodies
      against VZV are lacking in the majority of patients and between 6 and 12 months
      of age all specimens tested were negative. Beyond the first year of life
      antibodies against varicella were detected in four samples, probably due to
      previous VZV infection. In accordance with current recommendations, VZV
      vaccination should ideally be administered to children 9 months of age and older,
      although our data indicate that successful immunization may be possible at
      earlier age (6 months onwards) in certain circumstances.

PMID- 16459001
TI  - Superficial angiomyxoma of the floor of the mouth--a case report.
AB  - A report of a case of intra-oral superficial angiomyxoma of a middle aged
      Caucasian female. Angiomyxomas are distinctive soft tissue tumours associated
      with a high risk of local recurrence but lack metastatic potential. Only one
      intra-oral case [Chen YK, Lin LM, Lin CC, Yan YH. Myxoid tumor of the oral cavity
      with features of superficial angiomyxoma: report of a case. J Oral Maxillofac
      Surg 1998;56:379-82] appears to have been reported in the English language.

PMID- 16459002
TI  - Cry1Ab protein from Bt transgenic rice does not residue in rhizosphere soil.
AB  - Expression of Cry1Ab protein in Bt transgenic rice (KMD) and its residue in the
      rhizosphere soil during the whole growth in field, as well as degradation of the
      protein from KMD straw in five soils under laboratory incubation were studied.
      The residue of Cry1Ab protein in KMD rhizosphere soil was undetectable (below the
      limit of 0.5 ng/g air-dried soil). The Cry1Ab protein contents in the shoot and
      root of KMD were 3.23-8.22 and 0.68-0.89 microg/g (fresh weight), respectively.
      The half-lives of the Cry1Ab protein in the soils amended with KMD straw (4%,
      w/w) ranged from 11.5 to 34.3d. The residence time of the protein varied
      significantly in a Fluvio-marine yellow loamy soil amended with KMD straw at the
      rate of 3, 4 and 7%, with half-lives of 9.9, 13.8 and 18d, respectively. In
      addition, an extraction method for Cry1Ab protein in soil was developed, with
      extraction efficiencies of 46.4-82.3%.

PMID- 16459003
TI  - Detecting changes in insect herbivore communities along a pollution gradient.
AB  - The forests surrounding the urban areas of the Los Angeles basin are impacted by
      ozone and nitrogen pollutants arising from urban areas. We examined changes in
      the herbivore communities of three prominent plant species (ponderosa pine,
      California black oak and bracken fern) at six sites along an air pollution
      gradient. Insects were extracted from foliage samples collected in spring, as
      foliage reached full expansion. Community differences were evaluated using total
      herbivore abundance, richness, Shannon-Weiner diversity, and discriminant
      function analysis. Even without conspicuous changes in total numbers, diversity
      or richness of herbivores, herbivore groups showed patterns of change that
      followed the air pollution gradient that were apparent through discriminant
      function analysis. For bracken fern and oak, chewing insects were more dominant
      at high pollution sites. Oak herbivore communities showed the strongest effect.
      These changes in herbivore communities may affect nutrient cycling in forest
      systems.

PMID- 16459004
TI  - It's good to talk: adolescent perspectives of an informal, peer-led intervention
      to reduce smoking.
AB  - Although peer education has enjoyed considerable popularity as a health promotion
      approach with young people, there is mixed evidence about its effectiveness.
      Furthermore, accounts of what young people actually do as peer educators are
      scarce, especially in informal settings. In this paper, we examine the activities
      of the young people recruited as 'peer supporters' for A Stop Smoking in Schools
      Trial (ASSIST) which involved 10,730 students at baseline in 59 secondary schools
      in south-east Wales and the west of England. Influential Year 8 students,
      nominated by their peers, were trained to intervene informally to reduce smoking
      levels in their year group. The ASSIST peer nomination procedure was successful
      in recruiting and retaining peer supporters of both genders with a wide range of
      abilities. Outcome data at 1-year follow-up indicate that the risk of students
      who were occasional or experimental smokers at baseline going on to report weekly
      smoking at 1-year follow-up was 18.2% lower in intervention schools. This
      promising result was supported by analysis of salivary cotinine. Qualitative data
      from the process evaluation indicate that the majority of peer supporters adopted
      a pragmatic approach, concentrating their attentions on friends and peers whom
      they felt could be persuaded not to take up smoking, rather than those they
      considered to be already 'addicted' or who were members of smoking cliques.
      ASSIST demonstrated that a variety of school-based peer educators, who are asked
      to work informally rather than under the supervision of teaching staff, will
      engage with the task they have been asked to undertake and can be effective in
      diffusing health-promotion messages. Given the serious concerns about young
      people's smoking behaviour, we argue that this approach is worth pursuing and
      could be adapted for other health promotion messages.

PMID- 16459005
TI  - The pervasiveness of pharmaceutical expenditure inertia in the OECD countries.
AB  - This paper constructs and estimates an economic model for testing statistically
      the strength of possible 'expenditure inertia' as a plausible reason for rising
      drug expenditures of the Organization for Economic Cooperation and Development
      (OECD) countries. The ethical drugs sector in the OECD health care systems is
      increasingly targeted as the major culprit in the rising cost. Using multiple
      regression analysis, and the maximum likelihood estimation method, the data of
      each country (taken from OECD Health Data, 1997) were first tested for functional
      form optimality with the Box-Cox power family transformations model. Drug
      expenditure elasticities, at data means, were computed using each country's
      optimal regression model estimates. The results indicate that the traditionally
      fitted a priori limited functional form models (e.g., linear, log-log) are not
      globally consistent with data across countries. The effect of a one-period lagged
      real per-capita drug expenditure (capturing inertia or habit persistence) on
      current period real per-capita prescription expenditure is statistically
      significant in most countries. Pharmaceutical demands are inelastic, and tend to
      behave like a necessity, as expected. Since the significant effects of economic,
      demographic, and other drivers of high drug spending differ across countries,
      country-specific implications and policy suggestions for cost controls ought to
      differ.

PMID- 16459006
TI  - Chance, choice and control: lay debate on prenatal social sex selection.
AB  - Assisted reproductive technologies are typically positioned as increasing the
      range of choices open to the healthcare consumer, thereby enhancing 'reproductive
      freedom'. In this paper, we question the equivalence of reproductive choice and
      personal freedom in ethical theory, using results from a project investigating
      how lay people make ethical evaluations about the new genetic and reproductive
      technologies. We took the topic of social sex selection by preimplantation
      genetic diagnosis (PGD), and used group discussions and interviews in the north
      east of England to trace how lay people develop and express their ethical
      evaluations, and to identify the implicit or explicit normative framework that
      gave rise to their opinions on prenatal sex selection. There was a striking level
      of ambivalence towards choice in general and reproductive choice in particular.
      Participants offered few positive statements and numerous reasons why
      reproductive choice might be problematic. Our participants' argumentation shares
      with mainstream bioethical analysis the weighing of the possible harms of
      prenatal sex selection for social reasons against the harm of restricting
      reproductive freedom. However, unlike most secular-liberal bioethicists, many of
      our participants concluded that prenatal sex selection is undesirable because it
      is an expression of parental preference instead of a response to the future
      child's need. Our interpretation of their reasoning is that they work from an
      ideal of "good parents", one of the features of which is the relinquishing of
      control over their children, except to protect them from harm. This voluntary
      self-limitation does not indicate reduced autonomy, because parental autonomy can
      only operate within the limits set by this relational framework. We suggest that
      a model of relational autonomy captures our lay participants' framing of the
      problem better than a more traditional understanding of autonomy. Our study also
      shows that in appropriately structured discussion of bioethical issues, lay
      people can articulate reasons for their opinions that are grounded in
      sophisticated and morally relevant concepts.

PMID- 16459007
TI  - Monozygotic twins with Asperger syndrome: differences in behaviour reflect
      variations in brain structure and function.
AB  - A pair of monozygotic twins discordant for symptoms of Asperger syndrome was
      evaluated at the age of 13.45 years using psychometric, morphometric,
      behavioural, and functional imaging methods. The lower-functioning twin had a
      smaller brain overall, a smaller right cerebellum, and a disproportionately large
      left frontal lobe, and manifested almost no differential activation between
      distractors of high and low-congruence with target visual stimuli. The higher
      functioning twin manifested a typically autistic pattern of anterior deactivation
      and posterior hyperactivation in response to incongruent distractors, overlaid
      with a typically normal pattern of activation of superior frontal cortex. The
      morphometric results are consistent with known correlations between brain
      structure and behaviour in autism, and the physiological results suggest
      correspondences between structure and function.

PMID- 16459008
TI  - The characteristics of postcountershock pulseless electrical activity may
      indicate the outcome of CPR.
AB  - OBJECTIVES: When ventricular fibrillation is cardioverted to pulseless electrical
      activity (PEA), PEA has been regarded as a non-resuscitatable rhythm. Yet, recent
      reports and our earlier observations suggested otherwise. We therefore
      investigated outcomes after postcountershock PEA, and aimed to develop a scoring
      system for outcome classification at the onset of initial postcountershock PEA.
      METHODS: Data from 215 domestic pigs were retrospectively reviewed. VF was
      induced and untreated for 7 min. Defibrillation was attempted with up to three
      150 J biphasic shocks. Failing to restore spontaneous circulation (ROSC), 1 min
      of CPR preceded subsequent sequences of shocks until animals were resuscitated or
      for a total of 15 min. Fifty-nine instances of PEA followed defibrillation,
      including 29 animals that attained ROSC. RESULTS: ROSC animals required a shorter
      interval between the first shock and the initial postcountershock PEA, fewer
      shocks prior to onset of initial postcountershock PEA, demonstrated a greater VF
      wavelet amplitude prior to onset of initial PEA, smaller QRS intervals, and
      higher heart rates. Using Fisher's linear discriminant analysis, 79.3% of the
      ROSC and 63.3% of non-ROSC cases were predicted correctly. A total of 71.2% of
      all cases were classified correctly. CONCLUSIONS: Animals in which
      postcountershock PEA was converted to ROSC required shorter intervals from first
      shock to initial postcountershock PEA, fewer shocks prior to onset of initial
      postcountershock PEA, had greater VF wavelet amplitude prior to initial
      postcountershock PEA, small QRS intervals, and higher heart rates. Fisher's
      discriminant analysis is helpful in predicting the likelihood of ROSC for an
      individual animal presenting with postcountershock PEA.

PMID- 16459009
TI  - The effect of superoxide free radicals on human myometrial contractility in
      vitro.

PMID- 16459010
TI  - The computerized fetal heart rate analysis in post-term pregnancy identifies
      patients at risk for fetal distress in labour.
AB  - OBJECTIVE: To ascertain the diagnostic ability of a computerized fetal heart rate
      (FHR) analysis system in the identification of patients at risk of fetal distress
      in labour. STUDY DESIGN: Three hundred and two healthy post-term pregnancies were
      enrolled in a retrospective, cross-sectional study and subdivided into two
      groups, with (n=42) or without (n=260) fetal distress in labour. The last
      computerized FHR recording before onset of labour was analyzed. RESULTS: The two
      groups showed a significant difference only in FHR baseline and in percentage of
      small accelerations on total. The multivariate analysis showed that only the
      percentage of small accelerations was significantly related to the labour
      outcome. A higher diagnostic accuracy was obtained with use of neural network
      analysis, which allowed a sensitivity of 56%, specificity 91%, positive
      predictive value 53% and negative predictive value 92% with an overall accuracy
      of 86%. CONCLUSIONS: The increase in FHR baseline and in small FHR accelerations
      can be major factors in the prediction of subsequent fetal distress in healthy
      term fetuses. Use of neural networks seems to further improve the ability of
      computerized FHR analysis in the prediction of intrapartum distress.

PMID- 16459011
TI  - Dangerous placement of sutures in a vesico-segmentary plane in anterior placenta
      percreta.

PMID- 16459012
TI  - Efficacy and prognostic implications of administering adjuvant chemotherapy to
      patients with endometrial cancer that is confined to the uterus.
AB  - OBJECTIVE: The purpose of this study was to determine the value of prognostic
      factors and to assess the efficacy of adjuvant chemotherapy in patients with
      endometrial cancer confined to the uterus. STUDY DESIGN: Patients surgically
      stage IB, IC and II endometrial cancer according to the International Federation
      of Gynecology and Obstetrics were enrolled in this study. Stage IIIA tumors with
      positive peritoneal cytology, in the absence of other evidence of extra uterine
      disease, were also included. RESULTS: One hundred and sixty-seven patients
      fulfilled the eligibility criteria and 58 patients (34.7%) underwent combination
      chemotherapy. Disease recurrence occurred in 10 patients within a median time of
      17 months. Histologic grade 3 was an independent prognostic factor for both
      disease-free and overall survival rates. Fourteen of 23 patients with histologic
      grade 3 tumors received adjuvant chemotherapy consisting of cyclophosphamide (or
      etoposide), epirubicin and cisplatin (in 1989-1999) or paclitaxel, pirarubicin
      and carboplatin (in 2000-2002). The 5-year disease-free and overall survival
      rates for these individuals was 92.3%, a value significantly higher than those in
      patients who had not undergone chemotherapy (50.0%). CONCLUSIONS: Histologic
      grade of 3 is an independent prognostic marker in patients with endometrial
      cancer confined to the uterus and adjuvant chemotherapy might improve the
      survival rates in these patients.

PMID- 16459013
TI  - Unusual site of recurrence in epithelial ovarian carcinoma: Intercostal space
      metastasis.

PMID- 16459014
TI  - The value of cord blood interleukin-6 levels for predicting chorioamnionitis,
      funisitis and neonatal infection in term premature rupture of membranes.
AB  - OBJECTIVE: The objective was to determine whether the interleukin-6 (IL-6) level
      in umbilical cord blood can be used for the prediction of histologic
      chorioamnionitis, funisitis, fetal membrane cultures and neonatal infection.
      STUDY DESIGN: A case-control study was conducted on 30 controls (control group)
      and on 40 women with term premature rupture of the membranes (PROM group). The
      interleukin-6 concentration of cord blood was measured. Fetal membranes and
      newborn blood were cultured. Placentas were examined for histologic
      chorioamnionitis and funisitis. Receiver operator curve analysis was used to
      obtain a cut-off value of interleukin-6 concentration for predicting histological
      and clinical infection. RESULTS: The mean interleukin-6 level in cord blood was
      significantly higher in the PROM group (p=0.01). Histological chorioamnionitis
      and positive placental cultures were significantly higher in the PROM group
      (p=0.006 and 0.02, respectively). The PROM group had seven (17.5%) cases of
      funisitis and positive newborn blood cultures while neither was observed in the
      control group. A cord blood interleukin-6 level >29 pg/ml was found to have 84%
      sensitivity and 72.5% specificity for predicting positive placental cultures and
      74.1% sensitivity and 76.7% specificity for identifying cases of histologic
      chorioamnionitis. For predicting funisitis and positive newborn cord blood
      cultures a cord blood interleukin-6 level >39 pg/ml has 100% sensitivity and 81%
      specificity. CONCLUSION: Cord blood interleukin-6 level can be a tool for the
      evaluation of the extent of maternal-fetal infection and guides proper planning
      of the treatment.

PMID- 16459015
TI  - Interview with John Fitzpatrick--combination therapy for BPH: is this the way
      forward? Interview by Christine McKillop.

PMID- 16459016
TI  - PSA velocity and prostate cancer detection: the absence of evidence is not the
      evidence of absence.

PMID- 16459017
TI  - Prognostic significance of p53 mutation in suboptimally resected advanced ovarian
      carcinoma treated with the combination chemotherapy of paclitaxel and
      carboplatin.
AB  - The prognostic significance of p53 mutation, microsattelite instability and DNA
      mismatch protein hMLH1 expression in suboptimally resected advanced ovarian
      carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin
      was evaluated. The overall combination chemotherapy response rate and the
      complete remission rate were significantly higher among patients with mutant p53
      tumors than those with wild-type p53 tumors (35/42 (83%) vs. 32/58 (55%); P=0.003
      and 18/42 (43%) vs. 16/58 (28%); P=0.03, respectively). This tendency apparently
      existed in non-serous carcinoma, but not in serous carcinoma. Univariate analysis
      showed that the risk of death due to disease and risk of progression was
      significantly lower among patients with p53 mutation (P=0.0357 and 0.0281,
      respectively). However, the presence of microsattelite instability or loss of
      hMLH1 expression was not associated with either the clinical response or
      prognosis. Determining p53 mutational status can be useful in predicting
      therapeutic response to drugs in ovarian carcinoma, especially in non-serous
      tumors.

PMID- 16459018
TI  - Regulation of genes involved in dopamine transporter modulation by acute cocaine
      in rat striatum.
AB  - It is well established that acute administration of psychostimulants alters
      dopamine transport. However, the exact mechanism of this modulation is still
      unknown. In this study we examined the mRNA levels of several proteins involved
      in the various proposed processes following cocaine administration. The
      expression levels of several immediate early genes were also studied. This was
      performed in rat striatum using real-time quantitative PCR. As expected, a marked
      increase of the immediate early genes Fos, Egr1 and Egr3 was observed. Egr2 was
      also found up-regulated. Among the different genes studied only Synaptotagmin4 in
      the SNARE family and Synphilin1 in the synaptic vesicles binding family were
      modulated by acute cocaine treatment. Interestingly, acute amphetamine treatment
      did not increase either Synaptotagmin4 and Synphilin1 mRNA levels, although
      increases in early genes expression were noted.

PMID- 16459019
TI  - CBED contrast in the lower order Laue zone.
AB  - Contrast in a systematic arrangement of lower order Laue zone (LOLZ) beams is
      reported and analysed using a Bloch wave description. Observations are reported
      for hexagonal barium ruthenium zirconate (Ba4Ru3ZrO12) and barium ruthenium
      titanate (Ba3Ti2RuO9), both near the c-axis orientation. The specific scattering
      dynamics invoked by this diffraction geometry may have novel uses in the
      exploration of crystallographic parameters.

PMID- 16459020
TI  - The role of informatics in glycobiology research with special emphasis on
      automatic interpretation of MS spectra.
AB  - This paper reviews the current status of bioinformatics applications and
      databases in glycobiology, which are based on bioinformatics approaches as well
      as informatics for glycobiology where an explicit encoding of glycan structures
      is required. The availability of the complete sequence of the human genome has
      accelerated the systematic identification of so far unidentified glycogenes
      considerably in many areas of glycobiology using well-established bioinfomatics
      tools. Although there has been an immense development of new glyco-related data
      collections as well as informatics tools and several efforts have been started to
      cross-link and reference the various data deposited in distributed databases,
      informatics for glycobiology and glycomics is still poorly developed compared to
      the genomics and proteomics area. The development of algorithms for the automatic
      interpretation of MS spectra - currently, a severe bottleneck, which hampers the
      rapid and reliable interpretation of MS data in high-throughput glycomics
      projects - is reviewed. A comprehensive list of web resources is given. Several
      lines of progression are discussed. There is an urgent need for the development
      of decentralised input facilities of experimentally determined glycan structures.
      Simultaneously, agreements of standards for the structural description of glycans
      as well as formats for the related data have to be established. The integration
      of glycomics with genomics/proteomics has to increase.

PMID- 16459021
TI  - Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal
      human peripheral blood mononuclear cells: a Bcl-2 independent mechanism.
AB  - Polyphenols have been shown to induce apoptosis in a variety of tumor cells
      including leukemia both in vitro and in vivo. However, their action on normal
      human peripheral blood mononuclear cells (PBMCs) during oxidative stress remains
      to be explored. In this study, we have evaluated the anti-apoptotic and radical
      scavenging activities of dietary phenolics, namely caffeic acid (CA), ellagic
      acid (EA) and ferulic acid (FA). H2O2-induced apoptosis in normal human PBMCs was
      assayed by phosphotidylserine externalization, nucleosomal damage and DNA
      fragmentation. Incubation of PBMCs with 5 mM H2O2 led to increased Annexin-V
      binding to externalized phosphatidyl serine (PS), an event of pre-apoptotic stage
      of the cell. Peripheral blood mononuclear cells pretreated with phenolics could
      resist H2O2-induced apoptotic damage. Caffeic acid (60 and 120 microM) and EA
      (100 and 200 microM) caused no change in externalization of PS, whereas FA (100
      and 200 microM) increased externalization of PS in PBMCs treated with H2O2. The
      effects of phenolics were abolished to a large extent by culturing the PBMCs for
      24 h after washing the phenolics from the medium. Inhibitory activities of these
      phenolics on lipid peroxidation were in the order of EA<CA<FA. DPPH-scavenging
      activities of EA, CA and FA were found to be 31.2+/-1.36, 50+/-1.86 and 73.0+/
      1.58 microM respectively. Although, the phenolics significantly inhibited DNA
      damage and lipid peroxidation, they could not alter the Bcl-2 expression in
      PBMCs. In conclusion, the anti-apoptotic effect of EA, CA and FA in PBMCs seems
      to be through the Bcl-2 independent mechanism.

PMID- 16459023
TI  - Needle-sharing among young IV drug users and their social network members: The
      influence of the injection partner's characteristics on HIV risk behavior.
AB  - Injection drug use is a risk factor for HIV among adolescents and young adults,
      yet the interpersonal dynamics of needle-sharing among young injectors remain
      poorly understood. Research has focused on identifying the characteristics of
      individual IV drug users (IVDUs) that increase their risk of needle-sharing. Most
      studies have not taken into consideration IVDUs' decisions to share needles with
      certain partners but not with other partners. This study examined partner
      characteristics associated with needle-sharing among 96 male and 77 female young
      adult IV drug users who had shared needles previously. Men were most likely to
      share needles with partners who gave them emotional support, partners who they
      injected or who injected them, and partners with whom they had had sex. Women
      were most likely to share needles with partners who they injected or who injected
      them, partners with whom they had discussed HIV risk, and partners with whom they
      had had sex. Results indicate that needle-sharing occurs within the context of
      mutual injection rituals and close emotional and sexual relationships. Public
      health interventions are needed to help young IVDUs to avoid needle-sharing with
      intimate partners.

PMID- 16459022
TI  - Extracellular signal-regulated mitogen-activated protein kinase inhibitors
      decrease amphetamine-induced behavior and neuropeptide gene expression in the
      striatum.
AB  - The aim of this study was to determine whether inhibition of the extracellular
      regulated kinase signaling pathway decreases acute amphetamine-induced behavioral
      activity and neuropeptide gene expression in the rat striatum. Western blotting
      revealed that extracellular-regulated kinase1/2 phosphorylation was highly
      induced in the rat striatum 15 min after an acute amphetamine (2.5 mg/kg, i.p.)
      injection without altering the total amount of extracellular-regulated kinase
      protein. In a separate experiment, the systemic injection of SL327, a selective
      inhibitor of extracellular regulated kinase kinase that crosses the blood-brain
      barrier, 1 h prior to amphetamine administration decreased amphetamine-induced
      vertical and horizontal activity. Quantitative in situ hybridization
      histochemistry showed that SL327 abolished the high levels of preproenkephalin
      and preprodynorphin mRNA induced by amphetamine in the striatum with no
      alteration of their basal levels. In another set of experiments, the
      hyperlocomotor activity induced by amphetamine was reduced by pretreatment with
      intra-striatal infusion of U0126. U0126 also blocked the amphetamine-induced
      increases in phospho-extracellular-regulated kinase and preproenkephalin and
      preprodynorphin gene expression in the striatum. These data indicate that
      activation of the extracellular-regulated kinase cascade contributes to the
      behavioral effects and changes in striatal neuropeptide gene expression induced
      by acute amphetamine.

PMID- 16459024
TI  - Interactive dualism as a partial solution to the mind-brain problem for
      psychiatry.
AB  - With the collapse of the psychoanalytic and the behaviorist models, and the
      failure of reductive biologism to account for mental life, psychiatry has been
      searching for a broad, integrative theory on which to base daily practice. The
      most recent attempt at such a model, Engel's 'biopsychosocial model', has been
      shown to be devoid of any scientific content, meaning that psychiatry, alone
      among the medical disciplines, has no recognised scientific basis. It is no
      coincidence that psychiatry is constantly under attack from all quarters. In
      order to develop, the discipline requires an integrative and interactive model
      which can take account of both the mental and the physical dimensions of human
      life, yet still remain within the materialist scientific ethos. This paper
      proposes an entirely new model of mind based in Chalmers' 'interactive dualism'
      which satisfies those needs. It attributes the causation of all behaviour to
      mental life, but proposes a split in the nature of mentality such that mind
      becomes a composite function with two, profoundly different aspects. Causation is
      assigned to a fast, inaccessible cognitive realm operating within the brain
      machinery while conscious experience is seen as the outcome of a higher order
      level of brain processing. The particular value of this model is that it
      immediately offers a practical solution to the mind-brain problem in that, while
      all information-processing takes place in the mental realm, it is not in the same
      order of abstraction as perception. This leads to a model of rational interaction
      which acknowledges both psyche and soma. It can fill the gap left by the demise
      of Engel's empty 'biopsychosocial model'.

PMID- 16459025
TI  - Is the inverse association between Alzheimer's disease and cancer the result of a
      different propensity to methylate DNA?

PMID- 16459026
TI  - Ductal carcinoma in situ with microinvasion: clinicopathologic study and
      biopathologic profile.
AB  - Data regarding the biologic behavior and surgical management, in particular the
      axillary lymph node excision, of ductal carcinoma in situ with microinvasion
      (DCIS-MI) are controversial. Therefore, we decided to study the histopathologic
      characteristics, the biopathologic profile, as well as the follow-up of a group
      of patients with DCIS-MI. Thirty-one cases of DCIS-MI, 21 of whom were treated
      with axillary lymph node dissection, were studied. All cases were classified
      according to the Van Nuys classification, and the extension of DCIS was
      quantified. The biopathologic profile (ER, PR, MIB 1, p53, c-erbB-2) as well as
      the follow-up was also investigated. The results did not reveal any statistically
      significant differences between the two groups, and there was no statistically
      significant relationship between the extension of DCIS and the number of
      microinvasion (MI) foci or maximum MI diameter, or between Van Nuys
      classification of DCIS and again the number of MI foci or maximum MI diameter.
      DCIS-MI seems associated with good prognosis. None of the patients had relapses
      or metastases. Our data seem to suggest that the natural history of DCIS-MI
      resembles DCIS, and we, therefore, suggest that all the surgically removed area
      should be examined histologically to avoid missing foci of infiltrating breast
      cancer larger than 1mm.

PMID- 16459027
TI  - Chemotherapy-induced alterations in ovarian sex cord tumor with annular tubules
      (SCTAT): a diagnostic challenge.
AB  - We present a case of ovarian sex cord tumor with annular tubules (SCTAT) in a
      patient that received neoadjuvant chemotherapy with 3.5 years of follow-up. Neo
      adjuvant chemotherapy is a common practice in advanced cases of ovarian carcinoma
      and is rarely applied in nonepithelial ovarian tumors. Chemotherapy-induced
      morphologic alterations of the subsequently resected tissue samples are well
      recognized; in this case, chemotherapy-induced cytoarchitectural changes created
      diagnostic difficulties in the subsequently resected specimen.

PMID- 16459028
TI  - Characterization and expression analysis during embryo development of the mouse
      ortholog of MLL3.
AB  - We characterized the mouse ortholog of the human MLL3 gene and a 10.6 kb-Mll3
      transcript. The mouse Mll3 gene comprises 60 exons that encompass 226 kb in
      chromosome 5. The predicted protein of 3464 amino acids contains two PHD domains,
      an ATPase alpha_beta signature, an HMG, and a SET domain. We analyzed the
      expression of the Mll3 gene during the embryonic development of the mouse by
      whole-mount in situ hybridization. Low levels of expression throughout the embryo
      were first detected at 8.0 dpc. At this stage, the signal was already stronger in
      the forebrain neuroepithelium and absent in the heart. Next, expression outlined
      the ventral neural tube, the somites, the limbs, and the eye lens remaining at
      low levels throughout the embryo. By 13.0 dpc, expression became stronger in the
      spinal cord, in hand/foot plates, and in gonads. RT-PCR confirmed that Mll3 is
      expressed early during gametogenesis. We suggest that Mll3 is expressed early in
      pre-spermatogonia and then in spermatogonia.

PMID- 16459029
TI  - White-tailed deer (Odocoileus virginianus) develop spirochetemia following
      experimental infection with Borrelia lonestari.
AB  - Borrelia lonestari is considered a putative agent of southern tick-associated
      rash illness (STARI) and is known to occur naturally only in lone star ticks
      (Amblyomma americanum) and white-tailed deer (Odocoileus virginianus). We used a
      low passage isolate of B. lonestari (LS-1) to inoculate white-tailed deer, C3H
      mice, Holstein cattle, and beagles. Animals were monitored via examination of
      Giemsa and acridine orange stained blood smears, polymerase chain reaction (PCR),
      indirect fluorescent antibody (IFA) test, and/or culture isolation. Spirochetes
      were visualized in blood smears of both deer on days post-inoculation (DPI) 6, 8,
      12 and one deer on DPI 15. Whole blood collected from deer tested PCR positive
      starting on DPI 4 and remained positive as long as DPI 28. Both deer developed
      antibody titers of >64, with a maximum IFA titer of 1024. The organism was
      reisolated from the blood of both deer on DPI 6 and one deer on DPI 12. All
      isolation attempts from mice, calves, or dogs were negative, although one of
      seven mice was transiently PCR positive. Mice and dogs developed an IFA titer >
      or =64, while calves lacked a detectable antibody response. These preliminary
      experimental infection trials show that white-tailed deer are susceptible to
      infection with B. lonestari and develop a spirochetemia following needle
      inoculation, while C3H mice, calves, and dogs do not. Results suggest that deer
      may serve as a vertebrate reservoir host. Tick transmission studies are needed to
      confirm that this organism can be maintained in a natural cycle involving deer
      and A. americanum.

PMID- 16459030
TI  - Efficacy of a killed vaccine for the control of paratuberculosis in Australian
      sheep flocks.
AB  - A field trial was undertaken from 1999 until 2004 to determine the efficacy of a
      killed M. a. paratuberculosis vaccine, Gudair, for the control of ovine Johne's
      disease (OJD) in merino sheep run under Australian pastoral conditions. On each
      of three farms experiencing significant OJD losses (5-15% per annum), 200 merino
      lambs (age 1-4 months) were vaccinated, and 200 lambs were left unvaccinated.
      Animal assessments and sample collections were conducted twice yearly until 4 or
      5 years of age. The impact of vaccination on mortality rate, faecal shedding of
      M. a. paratuberculosis (by pooled and individual faecal culture), liveweight,
      wool productivity, vaccine injection site lesions and cellular (BOVIGAM) and
      humoral (PARACHEK) immunity was examined. Vaccination stimulated cell-mediated
      and humoral immune responses, reduced mortalities due to OJD by 90% and delayed
      faecal shedding for the first year post-vaccination. Thereafter, the prevalence
      of shedders among vaccinates was reduced by 90%. The numbers of M. a.
      paratuberculosis excreted by the vaccinated groups were also reduced by at least
      90% at most sampling times. However, high levels of excretion by vaccinates
      occurred on some occasions, and although only 7 of 600 vaccinates died from OJD,
      all 7 had multibacillary lesions. Thus there remains a risk that some vaccinated
      sheep will transfer the disease. Small reductions in liveweight were found in
      vaccinated lambs in the first year, but there was little effect on wool
      production. Vaccine injection site lesions were detected in almost 50% of sheep
      after 2 months, and these persisted for at least 4 years in 20-25% of vaccinates.
      Data from this trial enabled the registration of Gudair in Australia in 2002 and
      underpins the pivotal role of vaccination in the current management of OJD.

PMID- 16459031
TI  - Estimates of the cost and length of stay changes that can be attributed to one
      week increases in gestational age for premature infants.
AB  - OBJECTIVE: To estimate the potential savings, both in terms of costs and lengths
      of stay, of one-week increases in gestational age for premature infants. The
      purpose is to provide population-based data that can be used to assess the
      potential savings of interventions that delay premature delivery. DATA: Cohort
      data for all births in California in 1998-2000 that linked vital records data
      with those from hospital discharge abstracts, including those of neonatal
      transport. All infants with a gestational age between 24 and 37 weeks were
      included. There were 193,167 infants in the sample after deleting cases with
      incomplete data or gestational age that was inconsistent with birth weight.
      METHODS: Hospital costs were estimated by adjusting charges by hospital-specific
      costs-to-charges ratios. Data were aggregated across transport into episodes of
      care. Mean and median potential savings were calculated for increasing
      gestational age, in one-week intervals. The 25th and 75th percentiles were used
      to estimate ranges. RESULTS: The results are presented in matrix format, for
      starting gestational ages of 24-34 weeks, with ending gestational ages of 25 to
      37 weeks. Costs and lengths of stay decreased with gestational age from a median
      of $216,814 (92 days) at 24 weeks to $591 (2 days) at 37 weeks. The potential
      savings from delaying premature labor are quite large; the median savings for a 2
      week increase in gestational age were between $28,870 and $64,021 for gestational
      ages below 33 weeks, with larger savings for longer delays in delivery. Delaying
      deliveries <29 weeks to term (37 weeks) resulted in savings of over $122,000 per
      case, with the savings being over $206,000 for deliveries <26 weeks. CONCLUSIONS:
      These results provide population-based data that can be applied to clinical
      trials data to assess the impacts on costs and lengths of stay of interventions
      that delay premature labor. They show that the potential savings of delaying
      premature labor are quite large, especially for extremely premature deliveries.

PMID- 16459032
TI  - Freeze-drying of liposomes using tertiary butyl alcohol/water cosolvent systems.
AB  - The objective of this study was to obtain dehydrated liposomes using a novel
      procedure that involves freeze-drying (FD) of liposomes with TBA/water cosolvent
      systems. The effects of TBA on the integrity/stability of vesicles of HSPC (or
      SPC):Cholesterol (4:1) were investigated. TBA used as a cosolvent was detrimental
      to SPC liposomes, leading to increased particle size and leakage of trapped
      calcein. However, this was not the case for HSPC liposomes. The vesicle size and
      the retention of trapped calcein after lyophilization from cosolvents were
      similar to those after FD from water alone. Moreover, the addition of TBA can
      significantly enhance the sublimation of ice resulting in short FD cycles. The
      resulting lyophilized cake can form a loose powder upon agitation, which flowed
      well enough to be easily poured from the vial. Thus FD of HSPC liposomes using
      TBA/water cosolvent systems can provide sterile powder for specialized
      applications. In addition, in conjunction with a modified injection method, this
      FD technology might be used to produce dehydrated HSPC liposomes on a large
      scale.

PMID- 16459033
TI  - Biotin uptake and cellular translocation in human derived retinoblastoma cell
      line (Y-79): a role of hSMVT system.
AB  - The objective of this research was to investigate the presence of a specialized
      carrier-mediated system for biotin and delineate uptake mechanism and
      intracellular trafficking of biotin in the human derived retinoblastoma cell line
      (Y-79). Human derived retinoblastoma cell line, Y-79, was used for uptake
      studies. Uptake of [3H]Biotin was determined at various concentrations, pH,
      temperatures, in the absence of sodium and in the presence of other vitamins and
      metabolic inhibitors to delineate the mechanism of uptake. Uptake was determined
      in the presence of various intracellular regulatory pathways (protein kinase A &
      C, protein tyrosine kinase and calcium-calmodulin) modulators. Reverse
      transcription polymerase chain reaction (RT-PCR) was performed to confirm the
      molecular identity of human sodium-dependent multivitamin transporter (hSMVT).
      Uptake of [3H]Biotin in Y-79 cells were found to be saturable at micromolar
      concentration range, with apparent Km of 8.53 microM and Vmax of 14.12
      pmol/min/mg protein, but linear at nanomolar concentration range. Uptake was
      sodium, pH, temperature and energy-dependent, but chloride independent; inhibited
      by the structural analogue desthiobiotin, pantothenic acid and lipoic acid at
      milimolar concentrations and not at nanomolar concentrations. Uptake of
      [3H]Biotin was trans-stimulated by the intracellular biotin. Ca2+/calmodulin
      pathways appeared to play important roles in the regulation of riboflavin uptake
      in Y-79 cells via significant reduction in Vmax (66%) and Km (28%) of the uptake
      process. A human sodium-dependant multivitamin transporter, hSMVT, was identified
      by RT-PCR in Y-79. These studies demonstrated for the first time the existence of
      a human sodium dependant multivitamin transporter (hSMVT), a specialized carrier
      mediated system for biotin uptake, in human derived retinoblastoma cells.

PMID- 16459034
TI  - Preparation, characterization and in vivo evaluation of formulation of baicalein
      with hydroxypropyl-beta-cyclodextrin.
AB  - The interaction of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a poorly
      water-soluble flavonoid, baicalein (Ba), chemically 5,6,7-trihydroxy flavone in
      solution and solid-state was studied. Ba/HP-beta-CD solid systems were prepared
      by freeze-drying method. The formation of Ba/HP-beta-CD complex in aqueous
      solution was demonstrated by UV spectroscopy, while Ba/HP-beta-CD co-lyophilized
      product was characterized by differential scanning calorimetry (DSC) and X-ray
      diffractometry (XRD). Through complexation with HP-beta-CD, the solubility of Ba
      in neutral aqueous solution was improved significantly. The phase-solubility
      profile was AP-type, indicating the formation of higher-order complexes or
      complex aggregates. Ba/HP-beta-CD solid powders were amorphous and show a
      significantly improved dissolution rate in comparison with free Ba. Comparison of
      the pharmacokinetics between Ba/HP-beta-CD co-lyophilized product and free Ba was
      also performed in rats. The concentration of Ba and its mainly conjugated
      metabolite, 7-O-glucuronide of baicalein (BG) in rat plasma was determined by
      HPLC method. The in vivo results show that Ba/HP-beta-CD co-lyophilized product
      exhibits the similar pharmacokinetics as that of free Ba after intravenous
      administration. Ba/HP-beta-CD co-lyophilized product displays earlier tmax and
      higher Cmax of BG than free Ba after oral dosing. By comparing the AUC0-infinity
      of BG between oral dosing, the relative bioavailability of Ba/HP-beta-CD co
      lyophilized product to free Ba was 165.0%, which highlighted the evidence of
      significantly improved bioavailability of formulation of Ba with HP-beta-CD.

PMID- 16459035
TI  - Lateral line hair cell maturation is a determinant of aminoglycoside
      susceptibility in zebrafish (Danio rerio).
AB  - Developmental differences in hair cell susceptibility to aminoglycoside-induced
      cell death has been observed in multiple species. Increased sensitivity to
      aminoglycosides has been temporally correlated with the onset of
      mechanotransduction-dependent activity. We have used in vivo fluorescent vital
      dye markers to further investigate the determinants of aminoglycoside induced
      hair cell death in the lateral line of zebrafish (Danio rerio). Labeling hair
      cells of the lateral line in vivo with the dyes FM 1-43, To-Pro-3, and Yo-Pro-1
      served as reliable indicators of hair cell viability. Results indicate that hair
      cell maturation is a determinant of developmental differences in susceptibility.
      The age dependent differences in susceptibility to aminoglycosides are
      independent of the onset of mechanotransduction-dependent activity as measured by
      FM 1-43 uptake and independent of hair cell ability to take up fluorescently
      conjugated aminoglycosides.

PMID- 16459036
TI  - Rehabilitation plasticity: influence of hearing aid fitting on frequency
      discrimination performance near the hearing-loss cut-off.
AB  - Several studies have already demonstrated that patients with steeply sloping
      hearing loss of cochlear origin exhibit an improvement in frequency
      discrimination performance at or around the cut-off frequency. This enhancement
      cannot be explained in terms of peripheral mechanisms and should rather be
      interpreted in terms of central reorganization: i.e., injury-induced cortical
      plasticity. However, the reversibility and time course of such reorganization has
      not yet been described. The main goal of the present study was therefore to
      investigate the occurrence of rehabilitation plasticity associated with hearing
      aid fitting in human subjects. Nine subjects with steeply sloping hearing loss
      and who were candidates for auditory rehabilitation were tested. Discrimination
      limen-for-frequency (DLF) enhancement was investigated at the frequency with the
      best DLF (bDLF) for each individual subject before and during auditory
      rehabilitation (at 1 month, 3 months and 6 months). From 1 month on, frequency
      discrimination performance decreased significantly at the bDLF frequency, while
      remaining stable at other frequencies. This normalization may reflect a new
      central reorganization reversing the initial injury-induced changes in the
      cortical map. A correlation between subject's age and alteration in DLF at 1
      month was also found, suggesting that plasticity operates faster in younger
      patients.

PMID- 16459037
TI  - Maturation of the cortical auditory evoked potential in infants and young
      children.
AB  - The aim of this study was to evaluate the maturation of the cortical auditory
      evoked potential (CAEP) in humans. The participants in this experiment were 10
      newborns (<7 days), 19 toddlers (13-41 months), 20 children (4-6 years) and 9
      adults (18-45 years). CAEPs were obtained in response to low (400 Hz) and high
      (3000 Hz) tones and to the word token /baed/, all presented at 60 dB HL, at a
      rate of 0.22 Hz. Latency and amplitude measures were made for CAEP components P1,
      N1, P2 and N2 as a function of participant age, stimulus type and electrode
      montage. CAEP component latencies were relatively stable from birth to 6 years,
      but adults demonstrated significantly shorter latencies compared to infants and
      children. Components P1 and N2 decreased in amplitude, while components N1 and P2
      increased in amplitude from birth to adulthood. Words evoked significantly larger
      CAEPs in newborns compared to responses evoked by tones, but in other age groups
      the effects of stimulus type on component amplitudes and latencies were less
      consistent. There was evidence of immature tonotopic organisation of the
      generators of N1 when responses from infants and young children were compared to
      those of adults. The scalp distribution of components N1 and P2 was clearly
      different in newborns and toddlers compared to children and adults. In the
      younger groups, both N1 and P2 were uniformly distributed across the scalp but in
      children and adults these components showed more focal distributions, with
      evidence of response laterality increasing with maturity. The results of the
      present study describe, for the first time, CAEPs recorded from multiple scalp
      electrodes, for tones and speech stimuli, in infants and children from birth to 6
      years of age. Frequency-related differences in component amplitude were apparent
      at all ages reflecting development of tonotopic organisation of the CAEP neural
      generators.

PMID- 16459038
TI  - The botanical materia medica of the Iatrosophikon--a collection of prescriptions
      from a monastery in Cyprus.
AB  - This article analyses the botanical material that is contained in the
      Iatrosophikon, a collection of prescriptions from a monastery in Cyprus written
      down during the island's Ottoman period (1571-1878). A total of 494 herbal
      prescriptions were detected in the record and 231 plants belonging to 70
      different botanical families, as well as 21 various substances of botanical or
      mixed origin were identified. The distribution of the plants, the plant part
      used, the use of the material, and the mode of application are discussed.
      Parallels with other medical writings of the Greek-speaking Ottoman world suggest
      a local popular as well as a classical Greek and Byzantine influence. The latter
      is particularly supported by the relationship of the majority of the plants
      described to plants mentioned by Dioscorides. Additionally the question of what
      other sources might have contributed to this herbal knowledge is discussed. The
      results also show that most of the plants described originated from the island
      itself, only a minority of the botanical material presumably had to be imported.
      All the mentioned plants of local origin are also cited in modern
      ethnopharmacological studies on Cyprus, the Iatrosophikon demonstrates their use
      at a time from which no other written source of comparable detail exists.

PMID- 16459039
TI  - A role for physicians in ethnopharmacology and drug discovery.
AB  - Ethnopharmacology investigations classically involved traditional healers,
      botanists, anthropologists, chemists and pharmacologists. The role of some groups
      of researchers but not of physician has been highlighted and well defined in
      ethnopharmacological investigations. Historical data shows that discovery of
      several important modern drugs of herbal origin owe to the medical knowledge and
      clinical expertise of physicians. Current trends indicate negligible role of
      physicians in ethnopharmacological studies. Rising cost of modern drug
      development is attributed to the lack of classical ethnopharmacological approach.
      Physicians can play multiple roles in the ethnopharmacological studies to
      facilitate drug discovery as well as to rescue authentic traditional knowledge of
      use of medicinal plants. These include: (1) Ethnopharmacological field work which
      involves interviewing healers, interpreting traditional terminologies into their
      modern counterparts, examining patients consuming herbal remedies and identifying
      the disease for which an herbal remedy is used. (2) Interpretation of signs and
      symptoms mentioned in ancient texts and suggesting proper use of old traditional
      remedies in the light of modern medicine. (3) Clinical studies on herbs and their
      interaction with modern medicines. (4) Advising pharmacologists to carryout
      laboratory studies on herbs observed during field studies. (5) Work in
      collaboration with local healers to strengthen traditional system of medicine in
      a community. In conclusion, physician's involvement in ethnopharmacological
      studies will lead to more reliable information on traditional use of medicinal
      plants both from field and ancient texts, more focused and cheaper natural
      product based drug discovery, as well as bridge the gap between traditional and
      modern medicine.

PMID- 16459040
TI  - [Bacteriology of community acquired meningitis in Sfax, Tunisia (1993-2001)].
AB  - OBJECTIVE: The aim of this study was to analyze the distribution of bacteria
      responsible for community-acquired meningitis and the pattern of resistance of
      common species. DESIGN: All bacteriologically confirmed cases of community
      acquired meningitis were recorded between 1993 and 2001. RESULTS: Two hundred
      twenty-four cases of bacterial meningitis were recorded. The most frequent
      species were Haemophilus influenzae and Streptococcus pneumoniae followed by
      Neisseria meningitidis with respectively 37.1%, 32.1%, and 10.7% of cases. The
      yearly distribution of these bacteria did not show any epidemic peak.
      Enterobacteria and group B Streptococcus were the most frequently identified
      pathogens in neonatal meningitis. H. influenzae was the predominant microorganism
      in children between one month and five years of age, (66.4%) followed by S.
      pneumoniae (23.5%). S. pneumoniae was the predominant bacteria responsible fore
      more than half of the cases over five years of age. 28.8% of H. influenzae
      strains produced beta-lactamase. 27.2% of S. pneumoniae strains were less
      susceptible to penicillin. Resistance rates for amoxicillin and cefotaxime were
      respectively 10.6% and 7.5%. Only one strain of N. meningitidis (4.2%) presented
      with a decreased susceptibility to penicillin. CONCLUSIONS: In our study, H.
      influenzae and S. pneumoniae were the main microorganisms responsible for
      community-acquired meningitis. High resistance rates were found for these
      bacteria: 28.8% of H. influenzae to ampicillin and 27.2% of S. pneumoniae to
      penicillin.

PMID- 16459041
TI  - [Intra-amoebal development of Legionella pneumophila and the potential role of
      amoebae in the transmission of Legionnaires' disease].
AB  - Legionnaires' disease is one of the major infectious risks related to hospital
      water systems. It is commonly accepted, that the disease is transmitted to man
      mostly by inhalation of water aerosols contaminated by Legionella pneumophila.
      The ability of L. pneumophila to multiply intracellularly within some amoebae
      better explains the ecology, the pathogenicity, and the virulence of this
      bacterium against human alveolar macrophages. The presence of these amoebae in
      water systems located where cases of Legionnaire's disease broke out, partly
      explains the difficulty in eradicating Legionella. Some studies also show that
      amoebae can play a major role in the transmission of the disease to man. Some
      other studies point out that inhaled amoebae could be involved in the
      pathogenesis of Legionnaire's disease. Future strategies to prevent the
      transmission of Legionella will probably have to include efficient treatments
      against amoebae.

PMID- 16459042
TI  - [Legionellosis due to Legionella gormanii fortuitously found in a man with
      chronic lymphocytic leukemia: a case study and literature review].
AB  - Legionellosis due to other species than Legionella pneumophila is rarely
      described in human cases. It has been reported in immunocompromised patients with
      respiratory symptoms of pneumonia. We report a case of legionellosis in an
      immunocompromised 54-year-old man hospitalized for a blood transfusion. A routine
      pulmonary X- Ray was made and then a bronchoalveolar lavage was collected in
      which Legionella gormanii was identified. The diagnostic of legionellosis must be
      considered in all immunocompromised patients presenting with any pulmonary
      symptoms.

PMID- 16459043
TI  - [Reservoirs and transmission of Pseudomonas aeruginosa in intensive care unit].
AB  - OBJECTIVE: The authors had for aim to study reservoirs and transmission of
      Pseudomonas aeruginosa in an intensive care unit. DESIGN: A 6-month prospective
      descriptive study was made on water samples, samples from hands of health care
      workers, and clinical samples. P. aeruginosa strains were compared by pulsed
      field gel electrophoresis. RESULTS: Among the 211 patients hospitalized during
      the study, 14 (6.6%) were infected by P. aeruginosa. Out of 494 water samples, 80
      were contaminated by P. aeruginosa. The regularly disinfected water taps were
      more rarely contaminated than the others (P<10(-5)). Out of 140 hand samples, one
      showed contamination from an infected patient. CONCLUSIONS: aeruginosa cross
      transmission was observed during this study. We should follow strict hygienic
      precautions such as wearing gloves and performing thorough alcoholic rub
      disinfection. Water taps are often contaminated and require regular disinfection.

PMID- 16459044
TI  - Impairment of the ability of the injured aged brain in elevating urate and
      ascorbate.
AB  - Urate and ascorbate play a major role in the defense mechanism of the brain
      against oxidative damage induced by traumatic brain injury. The severity and
      extent of brain damage are known to increase with age. This may be due to
      different basal levels of endogenous antioxidants, and/or to impaired ability of
      the old brain to recruit and elevate the levels of antioxidants following injury.
      To investigate this hypothesis, we measured basal ascorbate and urate levels in
      the hippocampus, using microdialysis in young, adults and old rats, and performed
      closed head injury (CHI) in young (5-6 weeks) and old rats (19-20 months). Basal
      ascorbate, but not urate levels in old rats were significantly lower than in the
      adults. The ability of the old rats to increase ascorbate levels after CHI was
      significantly lower than that of the young ones, as indicated by lower levels of
      ascorbate and urate in the dialysate of old rats. This lower level of antioxidant
      mobilization in the old brain may explain the extended damage found in histology.
      Evaluation of hippocampal cell loss (p<0.05) and axonal degeneration in the
      corpus callosum showed more extensive damage in old as compared to young rats
      (chi(2)=4.25; p<0.05). These findings shed more light on the susceptibility of
      old rat brain to CHI-induced oxidative damage.

PMID- 16459045
TI  - A novel species of Xenorhabdus, family Enterobacteriaceae: Xenorhabdus indica sp.
      nov., symbiotically associated with entomopathogenic nematode Steinernema
      thermophilum Ganguly and Singh, 2000.
AB  - In the search for novel Xenorhabdus strains in a recently described nematode
      species, Steinernema thermophilum, three strains (strain 28(T) = DSM 17382(T),
      strain 42 = DSM 17383 and strain 43 = DSM 17384) were isolated from three
      independent isolation approaches from crushed mixture of infective juveniles. 16S
      rRNA gene sequence comparison of strains 28(T) and DSM 17383 indicated identity
      and the phylogenetic position pointed towards an individual taxon within the
      phylogenetic dendrogram of Xenorhabdus type strains. The nearest phylogenetic
      relatives of strain 28(T) were Xenorhabdus poinarii and Xenorhabdus szentirmaii
      (97.7% each). The three isolates were almost identical in reaction towards the
      API and BIOLOG substrate panels but differed in their reactions from those of the
      established type strains of the genus Xenorhabdus. These clear genomic and
      metabolic differences let us propose a new species, Xenorhabdus indica sp. nov.
      for the three clones. The type strain is strain 28(T), DSM 17382(T), CIP
      108830(T).

PMID- 16459046
TI  - Analysis of ginkgolides and bilobalide in food products using LC-APCI-MS.
AB  - A method was developed for the extraction and quantification of five marker
      compounds characteristic of Ginkgo biloba. Five ginkgo terpene trilactones:
      bilobalide and ginkgolides A, B, C, and J, were selected as marker compounds for
      this study. Initial studies produced a simple methanol extraction method for
      determination of gingko markers in solid dietary supplements. Five dietary
      supplements were analyzed and the results were later compared to the
      concentrations detected in the analysis of beverages. Beverage samples were
      prepared by extracting the ginkgo terpene trilactones using an optimized solid
      phase extraction (SPE) method. The extracts were analyzed using LC-atmospheric
      pressure chemical ionization (APCI)-MS in the negative ionization mode. The
      limits of detection of the extraction method ranged from 6.8 to 3.2 ng mL(-1).
      Using the optimized method, 14 drinks and 3 tea products were analyzed.
      Concentrations of total marker compounds in drinks ranged between 1685 and 21.4
      ng mL(-1) with individual ginkgo terpene trilactones being detected at ppb
      concentrations. Analysis of brewed tea products presented much higher total
      marker compound concentrations ranging from 8.12 and 16.6 microg mL(-1).
      Analytical results reproducibility data, and recovery of the SPE method are
      presented.

PMID- 16459047
TI  - Determination of hydralazine with flow injection chemiluminescence sensor using
      molecularly imprinted polymer as recognition element.
AB  - A novel flow injection chemiluminescence (CL) sensor for hydralazine
      determination using molecularly imprinted polymer (MIP) as recognition element is
      reported. Hydralazine-MIP was prepared through non-covalent copolymerization
      using methacrylic acid (MAA) monomer, hydralazine template and ethylene glycol
      dimethacrylate (EGDMA) cross-linker. Particles of the MIP were packed into a v
      shape glass tube for on-line adsorption of the analyte of hydralazine. The
      adsorbed hydralazine could be sensed by its great enhancing effect on the CL
      reaction between luminol and periodate. The CL intensity is linear to hydralazine
      concentration in the range from 2x10(-9) to 8x10(-7) g/mL. The detection limit is
      6x10(-10) g/mL (3sigma) and the relative standard deviation is 2.8% (n=7) for
      8x10(-9) g/mL hydralazine. The selective experiment showed that the selectivity
      and sensitivity of the CL method could be greatly improved when MIP was used as
      recognition element in the flow-injection CL sensor. The sensor was reversible
      and reusable. It could be used for more than 100 times. It has been used directly
      to determine the hydralazine in human urine.

PMID- 16459048
TI  - HPLC determination of polydatin in rat biological matrices: application to
      pharmacokinetic studies.
AB  - A reversed-phase high-performance liquid chromatographic (RPHPLC) method has been
      developed for the determination of polydatin (PD) in rat plasma, bile, urine,
      feces and tissue homogenates using 2,3,5,4'-tetrahydroxychrysophenine-beta-d
      glucoside as an internal standard. The sample pretreatment included
      deproteinization for plasma samples and a liquid-liquid extraction for bile,
      urine, feces and tissue homogenates. Separation was obtained on a C18 reversed
      phase column with the mobile phase consisting of methanol and water (35:65 v/v).
      The flow rate was 1 ml/min and the effluent was monitored at 310 nm. The method
      showed good linearity over the concentration ranges employed for various matrices
      (r > 0.998). The quantification limits of PD in rat plasma, bile, urine, feces
      and tissue homogenates were 0.0251, 0.126, 0.025 microg/ml, 0.189 and 0.0378
      microg/g, respectively. The accuracy and precision of the method were less than
      12.0% for the various matrices. No interferences from endogenous substances were
      found. The method was successfully applied to study the pharmacokinetics of PD in
      rats after intravenous administration.

PMID- 16459049
TI  - Immunohistochemical prognostic factors in resected colorectal lung metastases
      using tissue microarray analysis.
AB  - AIMS: Immunohistochemical prognostic factors of pulmonary metastatic colorectal
      cancer lesions have not been well investigated. The study was conducted to
      identify the immunohistochemical prognostic factors of metastasized colorectal
      cancer. METHODS: We immunohistochemically investigated the expression of insulin
      like growth factor-1 receptor (IGF1-R), E-cadherin, beta-catenin, and p53 using a
      tissue microarray in the surgical specimens of 86 metastatic lesions. RESULTS:
      The univariate analysis revealed E-cadherin and membrane beta-catenin positive to
      be prognostic factors. IGF1-R and p53 were not significantly associated with the
      patient's survival. In multivariate analysis, the reduced expression of E
      cadherin, aerogenous spread with floating cancer cell clusters and vascular
      invasion were independent prognostic factors. CONCLUSIONS: The reduced expression
      of E-cadherin in the pulmonary metastatic lesions was an independent predictor of
      poor survival after pulmonary metastasectomy.

PMID- 16459050
TI  - Predictors of outcome in patients with papillary thyroid carcinoma.
AB  - AIM OF THE STUDY: To evaluate prognostic factors with respect to the outcome in a
      consecutive series of patients with papillary thyroid carcinoma (PTC) treated at
      the same institution during a 20-year-period, and to evaluate further the
      predictive ability of outcome of the pTNM, AMES and MACIS prognostic systems in
      these patients. MATERIALS AND METHODS: Two hundred and twenty consecutive
      patients operated on for primary PTC at the Karolinska Hospital between 1980 and
      1999 were examined retrospectively. Patient and tumour characteristics at the
      time of surgery were compared to the patients' outcomes. Univariate and multiple
      logistic regression analyses were used to identify independently significant
      prognostic factors with respect to the outcome. In addition, the classification
      of the patients according to the pTNM, AMES and MACIS prognostic systems were
      compared to the outcomes. RESULTS: At the end of the follow-up period 201
      patients were still alive without disease, 6.5% had died from PTC and 2.5% were
      alive with persisting disease. In 16 patients, radical surgery could not be
      performed due to extensive tumour growth and/or distant metastases. Recurrences
      were detected in 14% of the patients considered as radically operated. The
      strongest independent predictors for local or distant recurrences and poor
      clinical outcome were the lack of radical surgery and increasing tumour size. In
      this investigation MACIS appeared to be the better system, regarding efficacy in
      predicting the outcome of PTC. CONCLUSION: Removal of all tumour tissue appears
      most important to a favorable outcome and in our patients MACIS appears the most
      useful prognostic system taking completeness of resection into account.

PMID- 16459051
TI  - Comparative cytoprotective activity of vitamin C, E and beta-carotene against
      chromium induced oxidative stress in murine macrophages.
AB  - The present study reports the cytoprotective efficacy of vitamin C, E and beta
      carotene against chromium (VI) induced oxidative stress in murine macrophages.
      Addition of chromium (VI) resulted in enhanced cytotoxicity as revealed by fall
      in neutral red uptake and increase in LDH release compared to control cells.
      Further there was an appreciable increase in apoptosis, ROS production and fall
      in reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide
      dismutase (SOD) activities. Chromium also inhibited macrophage proliferation and
      phagocytic activity. Addition of vitamin C but not vitamin E and beta-carotene
      inhibited chromium induced cytotoxicity, ROS generation and apoptosis. Vitamin C
      significantly inhibited NO production, enhanced macrophage proliferation and
      phagocytic activity while vitamin E and beta-carotene had marginal effect.

PMID- 16459052
TI  - TAK1 downregulation reduces IL-1beta induced expression of MMP13, MMP1 and TNF
      alpha.
AB  - The paper provides evidence that transforming growth factor-beta activated kinase
      1 (TAK1, MEKK7), a downstream mediator of IL-1beta signal transduction, plays an
      important role in the regulation of catabolic events and inflammatory processes
      in the context of degenerative joint diseases. We investigated the expression of
      TAK1 in human articular chondrocytes and in the murine growth plate by cDNA
      array, quantitative RT-PCR and immunohistochemistry, respectively. The human
      chondrosarcoma cell line SW1353 was stimulated with the proinflammatory cytokine
      IL-1beta. The subsequent expression of proteolytic enzymes and proinflammatory
      cytokines was quantified. TAK1 specific siRNA was used to study the influence of
      TAK1 downregulation on the expression of MMP-13, MMP1 and TNF-alpha. As a result
      we demonstrated the expression of TAK1 in normal and osteoarthritic human
      articular cartilage. Expression of TAK1 in the hypertrophic zone of the growth
      plate gave us a first evidence for a catabolic function of TAK1 concerning
      cartilage metabolism. By gene suppression with RNAi technology we could show that
      TAK1 downregulation leads to a 60-70% reduced release of TNF-alpha, a 40-50%
      reduced release of MMP13, and a 20-30% reduction of MMP1 release. As TNF-alpha is
      a main player in inflammatory processes, and MMP13 is one of the major proteases
      involved in cartilage degradation, our results suggests that TAK1 has an
      important regulatory role in the context of degenerative joint diseases and thus
      is an attractive drug target in attempts to reduce inflammation and suppress
      structural changes in OA induced by IL-1beta.

PMID- 16459053
TI  - Spermine increases arginase activity in the liver after carbon tetrachloride
      induced hepatic injury in Long-Evans rats.
AB  - Arginase is the enzyme which synthesizes urea and ornithine, a precursor from
      which putrescine, spermidine and spermine are formed. These natural polyamines
      have been implicated in cell growth, replication and wound healing. The present
      study evaluated the possibility that spermine increases arginase activity and
      reduces liver damage caused by carbon tetrachloride. Intraperitoneally injected
      spermine at a dose of 1 mg/kg after a single intragastric administration of
      carbon tetrachloride (1.6 ml/kg) increased arginase activity (6.30-7.79 microg
      urea/mg protein per min) (P<0.05) as well as total protein content (0.29-0.37
      mg/mg dry weight) in hepatic tissue, compared to the group which only received
      carbon tetrachloride. When liver cell damage was biochemically assessed, the
      carbon tetrachloride-treated group showed a 20-fold increase in serum glutamic
      oxaloacetate transaminase, compared to the control group (P<0.05), and this was
      significantly diminished by the administration of spermine (P<0.05). Serum
      triglycerides increased four times compared to the control group as a result of
      the carbon tetrachloride treatment and were diminished by spermine as well. These
      results indicate that spermine may play a role in the recovery of liver tissue
      after carbon tetrachloride-induced liver injury, maybe by increasing the
      synthesis of putrescine, a polyamine which has been found out to participate in
      the recovery of the hepatic tissue after an insult with carbon tetrachloride.

PMID- 16459054
TI  - Acute effects of hemodialysis on left ventricular function evaluated by tissue
      Doppler imaging.
AB  - Evidence exists that left ventricular function is impaired in chronic uremic
      patients. During hemodialysis (HD) treatment, myocardium undergoes electrolyte,
      hemodynamic and neuro-humoral stress; however, data about the acute changes on
      ventricular function are controversial. Aim of the present study was to evaluate
      the effect of a single hemodialysis session on left ventricular (LV) systolic and
      diastolic function using pulsed tissue Doppler imaging (TDI) sampled by
      echocardiography. The study group included 20 uremic patients (17 males, aged
      51+/-13 yrs) on maintenance HD, free from clinically overt cardiac dysfunction
      who underwent echocardiography with pulsed TDI 30 min prior and 30 min after a HD
      session. TDI was performed by placing the sample volume in the center of the
      basal lateral segment and the basal interventricular septum in the apical four
      chamber view. Myocardial systolic wave (S(m)) and early (E(m)) and atrial (A(m))
      diastolic waves were measured. On standard sonography examination, no significant
      changes in LV systolic function parameters were observed after HD, but the
      indices for LV diastolic function deteriorated significantly (peak E, 75.4+/-11.2
      vs. 58.8+/-12.5 cm/s, P<0.01; E/A ratio, 1.0+/-0.3 vs. 0.8+/-0.2, P<0.01).
      However, regarding TDI measures following HD, the patients exhibited a lower S(m)
      peak (septum: 7.6+/-1.1 vs. 5.9+/-0.8 cm/s; lateral wall: 7.7+/-1.7 vs. 6.8+/-1.2
      cm/s, P<0.001), a lower E(m) peak (septum: 8.3+/-1.6 vs. 6.3+/-1.7 cm/s; lateral
      wall: 10.2+/-2.4 vs. 7.1+/-1.9 cm/s, P<0.001), and a reduced E(m)/A(m) ratio
      (septum: 1.0+/-0.4 vs. 0.7+/-0.2; lateral wall: 1.2+/-0.5 vs. 0.7+/-0.2, P<0.001,
      respectively), as compared to pre-HD parameters. Of interest, peak E(m), and
      E(m)/A(m) ratio of the lateral wall were negatively related to ultrafiltration
      rate (r = -0.60, P<0.05 and -0.69, P<0.01, respectively). Our data indicate that
      a single hemodialysis session is associated with acute deterioration of diastolic
      and systolic parameters of myocardial function, as assessed by TDI. These
      reversible changes could be considered as a cardiac stunning that seems to be
      related to the ultrafiltration rate and then to the interdialysis weight gain.
      These findings suggest that low ultrafiltration volume and/or limited
      interdialytic weight gain are cardioprotective measures in hemodialysis patients.

PMID- 16459055
TI  - Psychometric properties of the French and English versions of the Claustrophobia
      Questionnaire (CLQ).
AB  - Research suggests that Claustrophobia, defined as the fear of enclosed spaces,
      may be better conceptualized as two separate, but related fears: (1) the fear of
      suffocation, and (2) the fear of restriction. The Claustrophobia Questionnaire
      (CLQ) is a self-report measure designed to assess these two fears. The original
      English version of the CLQ has demonstrated excellent psychometric properties.
      The purpose of the present study was to evaluate a French version of the CLQ for
      use in clinical and research settings and to replicate the psychometric findings
      of previous investigations of the English CLQ. Language-appropriate versions of
      the CLQ, as well as self-report measures of phobic, anxious and depressive
      symptomatology were distributed to undergraduate students at three Montreal,
      Quebec universities. Results show that the CLQ possesses strong psychometric
      properties in both languages, and that the English and French versions of the CLQ
      appear to measure identical constructs. These findings are discussed in terms of
      proposed applications of the CLQ.

PMID- 16459056
TI  - Identification and characterization of a novel Mt-retrotransposon highly
      represented in the female mouse germline.
AB  - The control of primordial follicle recruitment into the growing follicle
      population is a major limiting process in female reproduction. In order to gain
      insight into the molecular processes occurring at the time of primordial follicle
      activation, a subtractive hybridization analysis was performed between cDNAs
      prepared from temporally distinct mouse neonatal ovarian tissues that differed
      according to the state of primordial follicle activation. One highly represented
      clone associated with activation was an Mt retrotransposon-like sequence
      designated Mtfull, which was subsequently cloned and determined to be novel and
      restricted in expression to the ovary. The polyadenylated 1684-bp sequence has
      long terminal repeats, is predicted to be noncoding, and is the predominant Mti
      related sequence present in the mouse ovary. In situ hybridization further
      localized Mtfull expression to the oocyte and confirmed that expression is
      concomitant with follicle activation. Together with in silico data, we predict
      Mtfull plays an essential role in folliculogenesis through regulation of gene
      expression.

PMID- 16459057
TI  - Bactericidal activity of various antibiotics against biofilm-producing
      Pseudomonas aeruginosa.
AB  - Clinical isolates of Pseudomonas aeruginosa were collected from hospitals in
      Tehran, Iran, and identified using biochemical tests. A modified microtitre plate
      test was used to determine the biofilm-forming capacity of the isolates, measured
      with an enzyme-linked immunosorbent assay (ELISA) reader. Results showed that P.
      aeruginosa strain 214 was the most efficient at producing biofilm compared with
      the other strains. Observation of the bacterial biofilm on Teflon sheets and on a
      catheter using a scanning electron microscope showed greater biofilm formation on
      the catheter than on Teflon sheets. In this study, we investigated the
      bactericidal activity of fluoroquinolones, beta-lactams, macrolides and
      aminoglycoside. The results showed differences in the antibiotic susceptibility
      of planktonic and biofilm cell populations. Fluoroquinolones showed more potent
      activity than the other antibiotics, and biofilms were completely eradicated by
      treatment with 16 x the minimum inhibitory concentration (MIC) of ciprofloxacin
      and 64 x MIC of ofloxacin, whereas all biofilms survived 2560 microg/mL of
      imipenem and ceftazidime. Production of an exopolysaccharide matrix is one of the
      distinguishing characteristics of biofilms. It has been suggested that this
      matrix prevents access of antibiotics to the bacterial cells embedded in the
      community. In this study, we also evaluated the permeation of antibiotics through
      alginate of P. aeruginosa strain 214 using a sandwich cup method. Macrolides were
      most efficient, showing 100% penetration; fluoroquinolones and beta-lactams had a
      high permeation rate > 75%, whereas the rates for aminoglycosides were low
      (amikacin = 59%; gentamicin = 73%).

PMID- 16459058
TI  - Identification of three novel ostricacins: an update on the phylogenetic
      perspective of beta-defensins.
AB  - Three new beta-defensins, ostricacins-2, 3 and 4 (Osp-2, 3 and 4), have been
      successfully purified and characterised from ostrich heterophils in addition to
      ostricacin-1 (Osp-1). These peptides are composed of 36-42 amino acids with a
      molecular weight range of 4.70-4.98 kDa. In vitro, Osp-1, 3 and 4 were active
      against Escherichia coli O157:H7 and Staphylococcus aureus 1056 MRSA, whilst Osp
      2 was active against bacterial strains plus the yeast Candida albicans 3153A.
      Minimal inhibitory concentrations of the three ostricacins ranged from 0.96
      microg/mL to 12.03 microg/mL. Comparison with the known beta-defensins from
      mammalian and other avian species revealed that the four ostricacins shared eight
      conserved residues (six cysteines and two glycines), identified as the 'beta
      defensin core motif'. Comparisons of the sequence also indicated that beta
      defensins could have originated from a common beta-defensin-like ancestor that
      occurred before avian and mammalian lines diverged.

PMID- 16459059
TI  - Animal models with enhanced erythropoiesis and iron absorption.
AB  - The regulation of iron absorption is of considerable interest in mammals since
      excretion is minimal. Recent advances in iron metabolism have expounded the
      molecular mechanisms by which iron absorption is attuned to the physiological
      demands of the body. The pinnacle was the discovery and identification of
      hepcidin, a hepatic antimicrobial peptide that regulates absorption to maintain
      iron homeostasis. While the intricacies of its expression and regulation by HFE,
      transferrin receptor 2 and hemojuvelin are still speculative, hepcidin
      responsiveness has correlated negatively with iron absorption in different models
      and disorders of iron metabolism. Consequently, hepcidin expression is repressed
      to enhance iron absorption during stimulated erythropoiesis even in situations of
      elevated iron stores. Animal models have been crucial to the advances in
      understanding iron metabolism and the present review focuses on phenylhydrazine
      treated and hypotransferrinaemic rodents. These, respectively, experimental and
      genetic models of enhanced erythropoiesis highlight the shifting focus of iron
      absorption regulation from the marrow to the liver.

PMID- 16459060
TI  - Linking molecular motors to Alzheimer's disease.
AB  - It is currently thought that Alzheimer's disease develops due to aberrant
      generation of amyloid-beta peptides. However, the mechanisms underlying the
      aberrant generation of amyloid-beta peptides remain unknown. An emerging concept
      suggests that impaired axonal transport may play a pivotal role in the aberrant
      generation of amyloid-beta peptides. Here we review and discuss advances in
      understanding AD with the primary focus on the possible role of molecular motors
      and axonal transport in its pathogenesis.

PMID- 16459061
TI  - Development and virtual screening of target libraries.
AB  - The concomitant development of in silico screening technologies and of three
      dimensional information on therapeutically relevant macromolecular targets makes
      it possible to navigate in the structural proteome and to identify targets
      fulfilling user-defined queries. This review illustrates some in-house recent
      advances in the development of target libraries and how they can be browsed to
      unravel chemogenomic information.

PMID- 16459062
TI  - Synaptic plasticity, astrocytes and morphological homeostasis.
AB  - Recent discoveries suggest that astrocytes are an integral part of synaptic
      connections, as they sense and modulate synaptic activity. Moreover, there is
      evidence that astrocytes change the number of synaptic connections directly via
      synaptogenic signals or indirectly, by modifying the morphology of axons and
      dendrites. Here, we formulate the hypothesis that astrocytes mediate the
      morphological homeostasis of nerve cells, which is any adaptation of the
      morphology of a neuron to preserve its ability to respond to and generate
      synaptic activity during learning and memory-induced changes. We argue that
      astrocytes control neuronal morphology locally and across long-ranging assemblies
      of neurons and that on the other hand, astrocytes are part of the engram with
      plasticity-related changes affecting their morphology.

PMID- 16459063
TI  - Memoire: A framework for semantic interoperability of case-based reasoning
      systems in biology and medicine.
AB  - OBJECTIVE: Memoire is a framework for sharing and distributing case bases and
      case-based reasoning (CBR) systems in biology and medicine. METHODS AND MATERIAL:
      This paper first introduces the semantic Web approach to build a better Web where
      search engines, knowledge sources and servers, applications and services can
      live, work, and learn in cooperation. This semantic approach is particularly well
      suited for biomedical domains because significant ontologies have been developed
      there and constitute a sound basis for the standardization effort required for
      the semantic Web. Case-based reasoning systems in biomedicine have also benefited
      from these biomedical ontologies and models. RESULTS: This article demonstrates
      for three such systems how a semantics infused approach in CBR gives better, more
      accurate results in CBR. From this previous work on a semantic approach in CBR in
      biomedicine, the Memoire framework has evolved. CONCLUSION: Memoire proposes a
      unified OWL-based representation language for cases and case-based ontologies in
      biomedicine, where a Web Ontology Language (OWL) is a language to represent
      ontologies on the Web. Memoire provides a set of tools for building case-based
      reasoning systems compliant with its language. Memoire is extensible and can be
      adapted to different types of biomedical application domains, tasks, and
      environments. Memoire will permit bridging the gap within the multiple case-based
      reasoning systems dedicated to a single domain, and make available to agents and
      Web services the case-based competency of the CBR systems adopting its
      interchange language. The approach could be extended to other application domains
      of CBR.

PMID- 16459064
TI  - Case-based reasoning in the health sciences: What's next?
AB  - OBJECTIVES: This paper presents current work in case-based reasoning (CBR) in the
      health sciences, describes current trends and issues, and projects future
      directions for work in this field. METHODS AND MATERIAL: It represents the
      contributions of researchers at two workshops on case-based reasoning in the
      health sciences. These workshops were held at the Fifth International Conference
      on Case-Based Reasoning (ICCBR-03) and the Seventh European Conference on Case
      Based Reasoning (ECCBR-04). RESULTS: Current research in CBR in the health
      sciences is marked by its richness. Highlighted trends include work in
      bioinformatics, support to the elderly and people with disabilities,
      formalization of CBR in biomedicine, and feature and case mining. CONCLUSION: CBR
      systems are being better designed to account for the complexity of biomedicine,
      to integrate into clinical settings and to communicate and interact with diverse
      systems and methods.

PMID- 16459065
TI  - Phenotypic characterization of raw milk-associated psychrotrophic bacteria.
AB  - Among the 68 isolates, selected from 13 raw-milk samples in Finland (that
      originate from farm, truck or silo tanks), 60 (88%) were psychrotrophs. All the
      isolates were characterized by the determination of their spoilage and phenotypic
      features: proteolytic and lipolytic activities, the production of lecithinases
      and hemolytic factors were considered. Phenotypic characterization of the
      isolates was mainly performed with API 20NE and BIOLOG GN2 identification
      systems; the results were system-dependent, although the presence of
      representatives of the Pseudomonas genus (for the majority of the isolates) was
      suggested by both systems. The results of the numerical profile analyses by API
      20NE proposed that some strains might be members of Stenotrophomonas,
      Burkholderia and Acinetobacter genera; however, the identity of many isolates
      remained doubtful or controversial.

PMID- 16459066
TI  - The role of stroma in immune recognition and destruction of well-established
      solid tumors.
AB  - Well-established solid tumors (at least 14 days old and >1cm in average diameter)
      are extremely difficult to eradicate immunologically in mice. Most cancer
      patients that seek medical attention bear primary or metastatic tumors that have
      grown for longer and that are larger than the tumors we call established.
      Therefore, focusing research on the problems of rejecting well-established mouse
      tumors might help in the development of novel concepts and protocols for
      destroying tumors in patients. A particular problem with established cancers is
      that even when treatments induce temporary regression, cancer often recurs.
      Recent studies suggest that manipulation of the stromal microenvironment of these
      tumors can induce immune recognition and regression. Furthermore, targeting
      cancer cells as well as tumor stroma for immune destruction might be needed to
      prevent recurrence.

PMID- 16459067
TI  - Regulation of V(D)J recombination.
AB  - Adaptive immunity is intimately linked to the expression of antigen-specific
      immunoglobulin and T cell receptor genes and their recombination assembly from
      germline V, D and J gene segments. This developmentally regulated process relies
      on the activity of the Rag1-Rag2 recombinase, on accessibility of target gene
      segments and on monoallelic gene activation. Recent studies have revealed new
      mechanisms that, along with recombinase activity and locus accessibility, are
      likely to contribute to the control of V(D)J recombination, including target-site
      bias by the recombinase, RNA processing and chromosome positioning.

PMID- 16459068
TI  - T lineage progenitors: the earliest steps en route to T lymphocytes.
AB  - T lymphocyte development in the thymus is a tightly regulated stepwise process.
      The identification and characterization of the earliest T lineage progenitors and
      their downstream progeny now enables the study of important cellular and
      molecular mechanisms that control and regulate T lineage commitment and
      differentiation. Significant progress has been made recently on the developmental
      relationships of the various cells with T cell progenitor activity identified in
      mouse bone marrow, blood and thymus, and on the molecular regulation of
      progenitor homing to the thymus. The essential role of Notch-1 signalling in
      intrathymic T lineage commitment and subsequent T cell development has been
      clearly documented.

PMID- 16459069
TI  - The why and how of thymocyte negative selection.
AB  - The generation of T cell receptor (TCR) sequence diversity is the strength of
      adaptive immunity, yet is also the Achilles' heel. To purge highly self-reactive
      T cells from the immune system, generation of diversity has coevolved with a
      mechanism of negative selection. Recent studies have revealed new insights
      addressing the why and how of negative selection by examining situations in which
      negative selection has failed in human and animals models of autoimmunity. Both
      thymocyte extrinsic and intrinsic mechanisms are required to restrict the TCR
      repertoire to a non-autoreactive set. Negative selection also ensures that T
      cells emerge with receptors that are focussed on the peptide moiety of MHC
      peptide complexes.

PMID- 16459070
TI  - Nitrogen removal from recycled landfill leachate by ex situ nitrification and in
      situ denitrification.
AB  - A three-compartment system, comprising a landfill column with fresh municipal
      solid waste, a column with a well-decomposed refuse layer as methane producer,
      and a sequential batch reactor as ex situ nitrifying reactor, was employed to
      remove nitrogen from municipal solid waste leachate. Since food waste comprised a
      major portion of refuse collected in Shanghai, an intense hydrolysis reaction
      occurred and caused the rapid accumulation of ammonia nitrogen (NH(3)-N) and
      total organic carbon in the leachate. This paper discusses the role of the three
      mentioned units and the design and operation of the proposed system. With most
      NH(3)-N being converted to nitrite nitrogen (NO(2)(-)-N) or nitrate nitrogen
      (NO(3)(-)-N) by the nitrifying reactor, and with the well-decomposed refuse layer
      transforming most dissolved organic compounds to CO(2), carbonates and methane,
      it was found that the fresh refuse column could efficiently denitrify the
      hydrolyzed nitrogen to N(2) gas. The role of the three mentioned units and
      comments on the design and operation of the proposed system are also discussed.

PMID- 16459071
TI  - Agrobacterium-mediated genetic transformation of plants: biology and
      biotechnology.
AB  - Agrobacterium-mediated genetic transformation is the dominant technology used for
      the production of genetically modified transgenic plants. Extensive research
      aimed at understanding and improving the molecular machinery of Agrobacterium
      responsible for the generation and transport of the bacterial DNA into the host
      cell has resulted in the establishment of many recombinant Agrobacterium strains,
      plasmids and technologies currently used for the successful transformation of
      numerous plant species. Unlike the role of bacterial proteins, the role of host
      factors in the transformation process has remained obscure for nearly a century
      of Agrobacterium research, and only recently have we begun to understand how
      Agrobacterium hijacks host factors and cellular processes during the
      transformation process. The identification of such factors and studies of these
      processes hold great promise for the future of plant biotechnology and plant
      genetic engineering, as they might help in the development of conceptually new
      techniques and approaches needed today to expand the host range of Agrobacterium
      and to control the transformation process and its outcome during the production
      of transgenic plants.

PMID- 16459072
TI  - Patho-biotechnology: using bad bugs to do good things.
AB  - Pathogenic bacteria have evolved sophisticated strategies to overcome host
      defences, to interact with the immune system and to interfere with essential host
      systems. We coin the term 'patho-biotechnology' to describe the exploitation of
      these valuable traits in biotechnology, medicine and food. This approach shows
      promise for the development of novel vaccine and drug delivery systems, as well
      as for the design of more technologically robust and effective probiotic cultures
      with improved biotechnological and clinical applications. The genetic
      tractability of Listeria monocytogenes, the availability of the complete genome
      sequence of this intracellular pathogen, its ability to cope with stress, and its
      ability to traverse the gastrointestinal tract and induce a strong cellular
      immune response make L. monocytogenes an ideal model organism for demonstrating
      the patho-biotechnology concept.

PMID- 16459073
TI  - Comparative genomics as a tool for gene discovery.
AB  - With the increasing availability of data from multiple eukaryotic genome
      sequencing projects, attention has focused on interspecific comparisons to
      discover novel genes and transcribed genomic sequences. Generally, these
      extrinsic strategies combine ab initio gene prediction with expression and/or
      homology data to identify conserved gene candidates between two or more genomes.
      Interspecific sequence analyses have proven invaluable for the improvement of
      existing annotations, automation of annotation, and identification of novel
      coding regions and splice variants. Further, comparative genomic approaches hold
      the promise of improved prediction of terminal or small exons, microRNA
      precursors, and small peptide-encoding open reading frames--sequence elements
      that are difficult to identify through purely intrinsic methodologies in the
      absence of experimental data.

PMID- 16459074
TI  - Integrative oncology--what's in a name?

PMID- 16459075
TI  - Structural analysis of anti-tumor heteropolysaccharide GFPS1b from the cultured
      mycelia of Grifola frondosa GF9801.
AB  - A 21-kDa heteropolysaccharide, coded as GFPS1b, was obtained from the cultured
      mycelia of Grifola frondosa GF9801 by hot-water extraction, ethanol
      precipitation, and fractioned by DEAE Sepharose Fast-flow, followed by the
      purification with Sephadex G-100 column chromatography using an AKTA purifier. It
      exhibited more potent anti-proliferative activity on MCF-7 cells than other
      polysaccharide fractions. GFPS1b was an acidic polysaccharide with approximately
      16.60% protein and 4.3% uronic acid. Gas chromatography of absolute acid
      hydrolysate of GFPS1b suggested that it was composed of D-glucose, D-galactose,
      and L-arabinose with a molar ratio of 4:2:1. Periodate oxidation, Smith
      degradation, partial acid hydrolyzation, methylation analysis, FT-IR, and (1)H,
      (13)C NMR spectroscopy analysis revealed that GFPS1b had a backbone consisting of
      alpha-(1-->4)-linked D-galacopyranosyl and alpha-(1-->3)-linked D-glucopyranosyl
      residues substituted at O-6 with glycosyl residues composed of alpha-L-arabinose
      (1-->4)-alpha-D-glucose (1--> linked residues.

PMID- 16459076
TI  - Ternary biosorption studies of Cd(II), Cr(III) and Ni(II) on shelled Moringa
      oleifera seeds.
AB  - Competitive biosorption of Cd(II), Cr(III) and Ni(II) on unmodified shelled
      Moringa oleifera seeds (SMOS) present in ternary mixture were compared with the
      single metal solution. The extent of adsorption capacity of the ternary metal
      ions tested on unmodified SMOS was low (10-20%) as compared to single metal ions.
      SMOS removed the target metal ions in the selectivity order of Cd(II) > Cr(III) >
      Ni(II). Sorption equilibria, calculated from adsorption data, explained favorable
      performance of biosorption system. Regeneration of exhausted biomass was also
      attempted for several cycles with a view to restore the sorbent to its original
      state.

PMID- 16459077
TI  - Carbonic anhydrase inhibitors: cloning and sulfonamide inhibition studies of a
      carboxyterminal truncated alpha-carbonic anhydrase from Helicobacter pylori.
AB  - A library of sulfonamides/sulfamates has been investigated for the inhibition of
      the carboxyterminal truncated form of the alpha-carbonic anhydrase (CA, EC
      4.2.1.1) isolated from the gastric pathogen Helicobacter pylori (hpCA). This
      enzyme, incorporating 202 amino acid residues, showed a catalytic activity
      similar to that of the full length hpCA, with k(cat) of 2.35 x 10(5)s(-1) and
      k(cat)/K(M) of 1.56 x 10(7)M(-1)s(-1) at 25 degrees C and pH of 8.9, for the
      CO(2) hydration reaction. All types of activity for inhibition of the bacterial
      enzyme have been detected. Dorzolamide and simple 4-substituted
      benzenesulfonamides were weak hpCA inhibitors (inhibition constants, K(I)s, in
      the range of 830-4310 nM). Sulfanilamide, orthanilamide, some of their
      derivatives, and indisulam showed better activity (K(I)s in the range of 310-562
      nM), whereas most of the clinically used CA inhibitors, such as methazolamide,
      ethoxzolamide, dichlorophenamide, brinzolamide, topiramate, zonisamide, etc.,
      acted as medium potency hpCA inhibitors (K(I)s in the range of 124-287 nM). Some
      potent hpCA inhibitors were detected too (K(I)s in the range of 20-96 nM) such as
      acetazolamide, 4-amino-6-chloro-1,3-benzenedisulfonamide, 4-sulfanilyl-aminoethyl
      benzenesulfonamide, and 4-(2-amino-pyrimidin-4-yl)-benzenesulfonamide. Most of
      the investigated derivatives acted as better inhibitors of the human isoform hCA
      II than as hpCA inhibitors. Since hpCA is essential for the survival of the
      pathogen in acid, its inhibition by compounds such as those investigated here
      might be used as a new pharmacologic tool in the management of drug resistant H.
      pylori.

PMID- 16459078
TI  - Structural biology of cellular machines.
AB  - Multi-component macromolecular machines contribute to all essential biological
      processes, from cell motility and signal transduction to information storage and
      processing. Structural analysis of assemblies at atomic resolution is emerging as
      the field of structural cell biology. Several recent studies, including those
      focused on the ribosome, the acrosomal bundle and bacterial flagella, have
      demonstrated the ability of a hybrid approach that combines imaging,
      crystallography and computational tools to generate testable atomic models of
      fundamental biological machines. A complete understanding of cellular and systems
      biology will require the detailed structural understanding of hundreds of
      biological machines. The realization of this goal demands a concerted effort to
      develop and apply new strategies for the systematic identification, isolation,
      structural characterization and mechanistic analysis of multi-component
      assemblies at all resolution ranges. The establishment of a database describing
      the structural and dynamic properties of protein assemblies will provide novel
      opportunities to define the molecular and atomic mechanisms controlling overall
      cell physiology.

PMID- 16459079
TI  - Gas vesicles in actinomycetes?
AB  - Gas vesicles encoded by gvp genes provide buoyancy in many prokaryotes. In a
      recent Trends in Microbiology article entitled 'Gas vesicles in actinomycetes:
      old buoys in novel habitats?' van Keulen et al. documented the occurrence of gvp
      genes in soil-inhabiting actinomycetes but questioned whether any of them produce
      gas vesicles. We suggest that the protein encoded by gvpA in actinomycetes might
      be incompatible with the structure of the standard gas vesicle. Perhaps it has
      another role associated with the air-water interface.

PMID- 16459080
TI  - Let LuxS speak up in AI-2 signaling.
AB  - Quorum sensing is a process of bacterial cell-cell communication that uses small
      diffusible molecules to coordinate diverse behaviors in response to population
      density. The only quorum-sensing system shared by Gram-positive and Gram-negative
      bacteria involves the production of autoinducer-2 (AI-2). The AI-2 synthase LuxS
      is widely distributed among the Bacteria, which suggests that AI-2 is a language
      for interspecies communication. However, LuxS is also an integral component of
      the activated methyl cycle in bacteria. LuxS-based quorum sensing has been
      intensively studied in the past decade, mostly in relation to the AI-2 molecule
      and the downstream effects of luxS knockouts; few studies have focused on the
      gene and protein activity itself. Ongoing attempts to dissect the metabolic and
      signaling roles of LuxS leave little doubt that unraveling the regulation of luxS
      expression and cellular LuxS activity is the key to understanding LuxS-based
      quorum sensing.

PMID- 16459082
TI  - Proximal myotonic dystrophy associated with parkinsonism.
AB  - Although mental changes and cognitive disorders are seen frequently in myotonic
      dystrophy (MD) there are only three cases of MD associated with parkinsonism
      reported in the literature. We report another case of this extremely rare
      combination.

PMID- 16459083
TI  - Hemangioblastoma of the filum terminale.
AB  - A 52-year-old man presented with low backache, paraesthesiae and spasticity of
      both lower limbs. He had urinary retention and constipation. Investigations
      revealed a vascular intradural cauda equina-conus tumor. MRI scan demonstrated an
      enhancing mass at the second and third lumbar vertebral levels. There were
      multiple dilated and tortuous veins draining from both poles of the tumor.
      Digital subtraction spinal angiogram showed the tumor to be supplied mainly by
      the radiculo-medullary artery from first lumbar artery and dural branches of the
      second and third lumbar arteries. At surgery, after pre-operative embolization, a
      well-defined tumor with an orange hue and fleshy consistency was encountered
      arising from the filum terminale. The tumor was excised en bloc. A sporadic
      hemangioblastoma arising from the filum terminale should be considered as a rare
      cause of back pain and sciatica. Total excision of the tumor offers cure.

PMID- 16459084
TI  - Allodynia in the flank after thalamic stroke.
AB  - Lesions responsible for thalamic pain are often thought to involve the ventral
      posteromedial nucleus and ventral posterolateral nucleus of the thalamus. We
      describe two patients with allodynia and hyperpathia in the contralateral flank
      caused by a small lesion in the posteroventral part of the thalamus. When
      considered with the literature, involvement of the ventral posteroinferior
      nucleus may be responsible for this unique post-stroke pain syndrome.

PMID- 16459085
TI  - Clinical experience with rigid occipitocervical fusion in the management of
      traumatic upper cervical spinal instability.
AB  - Traumatic injuries of the craniovertebral junction or the upper cervical spine
      may result in occipitocervical (OC) or upper cervical spinal instability.
      Internal fixation can provide immediate stability to this region. Over a 6-year
      period, 16 patients with traumatic upper cervical spinal instability underwent a
      posterior approach OC fusion, using a plate and screw system, at the
      neurosurgical department of our institution. One patient died. The postoperative
      course of all the other patients was uncomplicated. At the most recent follow-up
      examination, all patients had satisfactory fusion. OC fusion with a plate and
      screw system is a safe and effective method for the treatment of traumatic
      craniovertebral and high cervical spine instability. Accurate imaging diagnosis
      and strict patient selection are the keys to a successful outcome.

PMID- 16459086
TI  - A preliminary study of the use of cage and plating for single-segment fusion in
      degenerative cervical spine disease.
AB  - Three different surgical methods were used to treat single-segment degenerative
      cervical spine disease, and the radiological and clinical outcomes were compared.
      The three groups compared were: 21 cases of anterior interbody fusion with iliac
      autograft (group A); 20 cases of anterior plate fixation with iliac autograft
      (group B); and 19 cases of carbon cage fusion and anterior plate fixation (group
      C). Bone union and changes in Cobb's angle and interbody space were evaluated
      using radiographs and clinical results by the method of Odom et al. Cobb's angle
      increased in group C, which was significantly better than the decrease in groups
      A and B. The interbody space decreased in group C, but was significantly less
      than the decrease in groups A and B. Carbon cage and anterior plate fixation can
      be used as an alternative surgical treatment modality for single-segment
      degenerative cervical spine and can provide early stability, maintain the
      interbody space and cervical lordosis, reduce operation time and minimize
      complications at the bone graft donor site.

PMID- 16459087
TI  - Intraoperative applications of intracranial pressure monitoring in patients with
      severe head injury.
AB  - From December 2002 to January 2004, 30 patients (20 men and 10 women; mean age
      36.8 years [+/- 14.9 years]) with preoperative Glasgow Coma Scale scores of 8 or
      less underwent emergency haematoma evacuation surgery and continuous intracranial
      pressure (ICP), cerebral perfusion pressure (CPP) and mean arterial blood
      pressure monitoring to determine ICP and CPP thresholds to predict patient
      outcomes. Receiver-operating characteristic (ROC) curves were plotted. Using the
      ROC curve, the diagnostic accuracy is given by the area under the curve and at
      the point on the curve farthest from the diagonal, which indicates the threshold
      value. The results showed that the initial ICP for unfavourable outcomes was 47.4
      +/- 21.4 mmHg, resulting in a CPP of 22.8 +/- 12.83 mmHg. The initial ICP for
      favourable outcomes was 26.4 +/- 10.1 mmHg, resulting in a CPP of 48.8 +/- 13.4
      mmHg. The CPP had the largest area under the ROC curve in all stages of the
      operation, corresponding to intraoperative CPP thresholds of 37 mmHg (initial),
      51.8 mmHg (intraoperative) and 52 mmHg (after scalp closure). The ROC curve
      analysis showed that CPP was a better predictor of outcome than ICP.

PMID- 16459088
TI  - Dural plasmacytoma mimicking meningioma in a patient with multiple myeloma.
AB  - Apart from calvarial infiltration, intracranial involvement in multiple myeloma
      is uncommon. Diffuse leptomeningeal invasion with or without parenchymal
      involvement is most common. Dural infiltration without involvement of the
      parenchyma, leptomeninges or skull is rare. The differential diagnosis of a dural
      plasmacytoma includes meningioma, which has a similar MRI appearance, metastasis,
      lymphoma and sarcoma of the dura mater. We present a patient with multiple
      myeloma presenting with an intracerebral mass mimicking a meningioma on MRI.
      Multiple myeloma had been diagnosed seven years previously. The patient presented
      with headache and speech disturbance 12 months after autologous peripheral stem
      cell transplantation for recurrence of multiple myeloma. MRI revealed a left
      temporal extra-axial mass with a dural tail mimicking meningioma.
      Histopathological examination of the mass after excision showed multiple myeloma
      immunopositive for IgG, kappa light chain and CD38. There was no recurrence after
      postoperative radiotherapy. Plasmacytoma should be considered in the differential
      diagnosis of a solitary dural mass, particularly in a patient with multiple
      myeloma.

PMID- 16459089
TI  - CT perfusion source images improve identification of early ischaemic change in
      hyperacute stroke.
AB  - CT perfusion scanning produces dynamic contrast-enhanced brain images, but to
      generate and interpret the colour maps of cerebral perfusion from these source
      images requires specialist neuroimaging knowledge. We hypothesized that
      physicians without such training might still utilise the CT perfusion source
      images (CTPSI) to diagnose early ischaemic change. Fifteen patients had cerebral
      non-contrast CT (NCCT) and perfusion CT within 6 hours of hemispheric stroke
      onset. We tested 15 non-stroke clinicians and radiology trainees, plus three
      experts, in assessing the presence and extent of early ischaemic change on NCCT
      versus CTPSI. Day 5-7 CT or MRI was used as the gold standard. Agreement with
      follow-up imaging was poor for both detection, and extent of early ischaemic
      change on NCCT (kappa = 0.01-0.11). There was a marked improvement in agreement
      for both the presence and extent of early ischaemic change on CTPSI (kappa = 0.67
      0.83). CTPSI were much more accurate than NCCT in identifying acute ischaemic
      change. 'Less expert' users accurately identified major early ischaemic change on
      acute CTPSI. These findings suggest that such physicians might utilise CTPSI to
      screen potential thrombolysis candidates.

PMID- 16459090
TI  - Double-segment Wilhelm Tell technique for anterior lumbar interbody fusion in
      unstable isthmic spondylolisthesis and adjacent segment discopathy.
AB  - The Wilhelm Tell technique is a novel instrumented anterior lumbar interbody
      fusion (ALIF) procedure using a specially designed composite carbon fibre cage
      and a single short-threaded cancellous screw that obliquely passes through the
      upper adjacent vertebral body, the interbody cage itself and through the lower
      adjacent vertebral body. This single-stage fusion method, which is in principle a
      combination of the Louis technique and modern cage surgery, is reported to have a
      lower rate of pseudoarthrosis formation than stand-alone cage techniques. In
      addition, it eliminates both the surgical trauma of paravertebral muscle
      retraction and the risk of neural damage by poorly located pedicular screws. This
      anterior approach allows decompression of neural structures within the anterior
      part of the spinal canal and the foraminal region. It is the purpose of this case
      report, to present the successful application of this novel technique in a 32
      year-old woman who concurrently suffered from severe instability-related back
      pain from L4/5 isthmic spondylolisthesis and marked L5/S1 degenerative disc
      disease.

PMID- 16459091
TI  - Looking for clues.
AB  - At certain moments in clinical practice, one can seem to possess the powers of a
      Sherlock Holmes to search out clues and deduce the diagnosis. Many neurologists
      are aware of links between the workings of detective fiction and the methods of
      problem-solving in neurological cases. One similarity concerns the professional
      counterpart of the conventional detective story, the single case report.

PMID- 16459092
TI  - Spike-wave stupor in a patient with metabolic disorder.
AB  - We report a 79-year-old woman with a decreased level of consciousness.
      Investigation revealed an elevated serum ammonia and a portal-systemic shunt on
      angiography. Thus, her symptoms were thought to be due to metabolic
      encephalopathy. Her electroencephalogram (EEG) showed bilaterally synchronous
      runs of three-phase waves consistent with the triphasic waves typically seen in
      metabolic encephalopathy. However, after intravenous administration of diazepam,
      the EEG abnormalities improved; indicating that her decreased consciousness was
      of epileptic etiology, consistent with spike-wave stupor. Therefore, even in the
      presence of a clearly defined metabolic disorder, triphasic waves on the EEG may
      not be due to metabolic encephalopathy; they may reflect an epileptic state
      precipitated by the metabolic disorder.

PMID- 16459093
TI  - Scanning electron microscopy studies of sensilla and other structures of the head
      of Polygenis (Polygenis) tripus (Siphonapera: Rhopalopsyllidae).
AB  - The external morphology of the head and appendages of adult Polygenis (Polygenis)
      tripus [Jordan, K., 1933. Descriptions of Siphonaptera. Nov. Zool. 39, 66-69]
      (Siphonaptera: Rhopalopsyllidae) was described based on scanning electron
      microscopy. Chaetal, trichoid and basiconic sensilla were encountered and their
      positions noted, comparisons being made between male and female specimens. Those
      of the basiconic type were particularly abundant on the frontal and occipital
      regions of the head and were surrounded by several pores, indicating the
      considerable sensory importance of these areas. Frontal tubercle was observed as
      a projection emerging from a depression in the frontal head region. The antennae
      of males were more developed, presenting greater number of sensilla on the scape
      and about 370 spatulate setae on the internal surface of the clava. Three large
      chemoreceptors, digitate sensilla ca. 11-13 microm were observed on the lateral
      surface of the antennal clava of both sexes between antennomeres 4-7. Females
      present a characteristic distribution of basiconic sensilla on the dorsal margin
      and median external surface of the clava. Trichoid sensilla were observed on all
      segments of the maxilary palps while basiconic sensilla were only recognized on
      the distal three segments.

PMID- 16459094
TI  - Measurement of the natural radioactivity at the international high energy
      stereoscopic system (HESS) project in Southern Africa.
AB  - The concentrations of the natural radionuclides 40K, 238U, and 232Th in soil
      samples taken from the international high energy stereoscopic system (HESS)
      project in Namibia have been determined using an HPGe detector and found to vary
      from 10.8 +/- 1.4 to 26.4 +/- 1.8 Bq kg(-1) for 238U, 12.8 +/- 2.4-52.3 +/- 3.7
      Bq kg(-1) for 232Th and 212.1 +/- 12.1-683.8 +/- 27.1 Bq kg(-1) for 40K. The
      corresponding annual effective dose equivalent is 0.06 +/- 0.01 mSv y(-1) which
      is less than the limit of 1 mSv y(-1) recommended for the public by the ICRP.

PMID- 16459095
TI  - Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage.
AB  - Recent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in
      acute brain injury and ischemia. HO2, the main enzyme to degrade the pro-oxidant
      heme, was tested for its neuroprotective ability in postnatal neuronal cell
      cultures and in a model of collagenase-induced intracerebral hemorrhage. Genetic
      deletion of HO2 rendered cultured neurons 32% (P < 0.01) more vulnerable to hemin
      induced toxicity, increased brain injury volume in mice by 30% (P < 0.05) at day
      1 and by 67% (P < 0.05) at day 3, and worsened neurologic functions by 26% (P <
      0.05) at day 1 and by 38% (P < 0.05) at day 3 following exposure to free heme
      liberated from hemorrhage. Together, these findings suggest that HO2 is a crucial
      neuroprotective enzyme in detoxifying high levels of heme from the brain and that
      further work is warranted to investigate potential therapeutic strategies that
      target HO2 in intracerebral hemorrhage.

PMID- 16459096
TI  - Neuroapoptosis in the infant mouse brain triggered by a transient small increase
      in blood alcohol concentration.
AB  - Exposure of infant rats or mice to ethanol on a single occasion during the period
      of rapid synaptogenesis can cause extensive apoptotic neurodegeneration
      throughout the developing CNS. Prior studies were designed to assess the effects
      of large doses of ethanol (comparable to heavy binge drinking), whereas in the
      present study, we sought to determine what magnitude and duration of blood
      ethanol elevation are required to trigger a minimal neuroapoptotic response. We
      found that a rise in blood ethanol to a level in the range of 50 mg/dl for a
      duration of 30 to 45 min was sufficient to trigger a significant neuroapoptosis
      response deleting approximately 20,000 neurons per infant mouse brain. Since
      blood ethanol elevations in this range are commonly achieved by humans in a
      social drinking context, a mother with only a moderate drinking habit might
      expose her fetus to such elevations on multiple occasions during pregnancy.

PMID- 16459097
TI  - Protective effects of isoliquiritigenin in transient middle cerebral artery
      occlusion-induced focal cerebral ischemia in rats.
AB  - Epidemiological studies indicate that the intake of flavonoids is inversely
      associated with risk of stroke, cardiovascular diseases and cancer.
      Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza
      glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet, anti
      tumor, anti-allergic, antiviral activities and estrogenic properties. However,
      there is no report on the effects of ISL in cerebral ischemia. Evidence
      demonstrate that the impaired energy metabolism and the excessive generation of
      reactive oxygen radicals (ROS) contribute to the brain injury associated with
      cerebral ischemia. In the present study, the protective effects of ISL were
      investigated in transient middle cerebral artery occlusion (MCAO)-induced focal
      cerebral ischemia-reperfusion injury in rats. Male Sprague-Dawley rats were
      divided into five groups: sham-operated group, vehicle-pretreated group, and
      three ISL-pretreated groups (5, 10 and 20 mg kg(-1), i.g.). ISL were administered
      once a day, for 7 days prior to ischemia. The rats were subjected to 2 h right
      MCAO via the intraluminal filament technique and 22 h reperfusion. Pretreatment
      with ISL significantly reduced the cerebral infarct volume and edema and produced
      significant reduction in neurological deficits. In this study, in order to
      clarify the mechanism of ISL's protection against cerebral ischemia damage,
      cerebral energy metabolism, brain Na+K+ATPase activity, malondialdehyde (MDA)
      content and antioxidant enzyme activities were measured. ISL pretreatment
      increased the brain ATP content, energy charge (EC) and total adenine nucleotides
      (TAN) in a dose-dependent manner. The brain Na+K+ATPase activity was protected
      significantly by pretreatment of ISL for 7 days. Pretreatment with ISL
      significantly inhibited the increases of brain MDA content and prevented the
      activities of brain superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GSH-Px) from declines caused by cerebral ischemia-reperfusion. All
      these findings indicate that ISL has the protective potential against cerebral
      ischemia injury and its protective effects may be due to the amelioration of
      cerebral energy metabolism and its antioxidant property.

PMID- 16459098
TI  - Ginkgo biloba inhibits bleomycin-induced lung fibrosis in rats.
AB  - Oxidative stress has been implicated in the pathogenesis of bleomycin-induced
      lung fibrosis and many antioxidant agents have been studied for prevention and
      treatment of the disease in animals and humans. We therefore examined whether
      Ginkgo biloba (Gb), a flavonoid-rich antioxidant, inhibits bleomycin-induced lung
      fibrosis in rats. Male Sprague-Dawley rats were given a single dose of bleomycin
      (2.5 mg/kg, intratracheally) in pulmonary fibrosis groups and saline in controls.
      First dose of Gb was given a day before the bleomycin injection and continued
      until sacrifice. At day 14, fibrotic changes in lung were estimated to occur by
      Aschoft's criteria and lung hydroxyproline content. Bleomycin challenge provoked
      severe pulmonary fibrosis with marked increase in hydroxyproline content of lung
      tissue and typical histological findings, which is prevented by Gb.
      Hydroxyproline level was significantly higher (13.51+/-0.87 mg/g dried tissue) in
      bleomycin treated rats than controls (9.2+/-1.33), and its level was remained to
      the control levels (7.38+/-0.76) in rats treated with prophylactic Gb. On the
      other hand, bleomycin injection significantly reduced activities of glutathione
      peroxidase, superoxide dismutase and catalase in lung tissue which is prevented
      by Gb. Also, bleomycin injection resulted in a marked increase of malondialdehyde
      and nitrite level which is attenuated by Gb. The data suggest that Gb has a
      potent antioxidant activity in the model of bleomycin-induced lung fibrosis in
      rats, and therefore has a potent antifibrotic activity against bleomycin-induced
      lung fibrosis model in rats.

PMID- 16459099
TI  - The use of rabbit polyclonal antibodies to assess neoantigenicity following viral
      reduction of an alpha-1-proteinase inhibitor preparation.
AB  - The objective of this study was to determine whether the viral reduction
      processes of nanofiltration and solvent/detergent treatment used in the
      manufacture of alpha-1 proteinase inhibitor (API) cause neoantigenic changes.
      Polyclonal antibodies were raised in rabbits against the treated API and
      quantitatively absorbed with an affinity column containing API that had not
      undergone viral reduction treatment. Antibodies before and after absorption were
      measured in a validated ELISA using the immunogen for antibody capture.
      Antibodies against novel API epitopes were not found after antiserum from rabbits
      inoculated with treated API was absorbed with untreated API. A positive control,
      consisting of serum obtained from rabbits inoculated with trinitrophenylated API,
      showed substantial amounts of measurable antibody following absorption with
      untreated API. The results suggest that the viral reduction process used does not
      result in the creation of API neoantigens.

PMID- 16459101
TI  - Mechanisms of antimicrobial peptide action: studies of indolicidin assembly at
      model membrane interfaces by in situ atomic force microscopy.
AB  - We report here on an in situ atomic force microscopy study of the interaction of
      indolicidin, a tryptophan-rich antimicrobial peptide, with phase-segregated
      zwitterionic DOPC/DSPC supported planar bilayers. By varying the peptide
      concentration and bilayer composition through the inclusion of anionic lipids
      (DOPG or DSPG), we found that indolicidin interacts with these model membranes in
      one of two concentration-dependent manners. At low peptide concentrations,
      indolicidin forms an amorphous layer on the fluid domains when these domains
      contain anionic lipids. At high peptide concentrations, indolicidin appears to
      initiate a lowering of the gel-phase domains independent of the presence of an
      anionic lipid. Similar studies performed using membrane-raft mimetic bilayers
      comprising 30mol% cholesterol/1:1 DOPC/egg sphingomyelin revealed that
      indolicidin does not form a carpet-like layer on the zwitterionic DOPC domains at
      low peptide concentrations and does not induce membrane lowering of the liquid
      ordered sphingomyelin/cholesterol-rich domains at high peptide concentration.
      Simultaneous AFM-confocal microscopy imaging did however reveal that indolicidin
      preferentially inserts into the fluid-phase DOPC domains. These data suggest that
      the indolicidin-membrane association is influenced greatly by specific
      electrostatic interactions, lipid fluidity, and peptide concentration. These
      insights provide a glimpse into the mechanism of the membrane selectivity of
      antibacterial peptides and suggest a powerful correlated approach for
      characterizing peptide-membrane interactions.

PMID- 16459100
TI  - A model-based parallel origin and orientation refinement algorithm for cryoTEM
      and its application to the study of virus structures.
AB  - We present a model-based parallel algorithm for origin and orientation refinement
      for 3D reconstruction in cryoTEM. The algorithm is based upon the Projection
      Theorem of the Fourier Transform. Rather than projecting the current 3D model and
      searching for the best match between an experimental view and the calculated
      projections, the algorithm computes the Discrete Fourier Transform (DFT) of each
      projection and searches for the central section ("cut") of the 3D DFT that best
      matches the DFT of the projection. Factors that affect the efficiency of a
      parallel program are first reviewed and then the performance and limitations of
      the proposed algorithm are discussed. The parallel program that implements this
      algorithm, called PO(2)R, has been used for the refinement of several virus
      structures, including those of the 500 Angstroms diameter dengue virus (to 9.5
      Angstroms resolution), the 850 Angstroms mammalian reovirus (to better than 7A),
      and the 1800 Angstroms paramecium bursaria chlorella virus (to 15 Angstroms).

PMID- 16459102
TI  - Structure of chorismate synthase from Mycobacterium tuberculosis.
AB  - In bacteria, fungi, plants, and apicomplexan parasites, the aromatics compounds,
      such as aromatics amino acids, are synthesized through seven enzymes from the
      shikimate pathway, which are absent in mammals. The absence of this pathway in
      mammals make them potential targets for development of new therapy against
      infectious diseases, such as tuberculosis, which is the world's second commonest
      cause of death from infectious disease. The last enzyme of shikimate pathway is
      the chorismate synthase (CS), which is responsible for conversion of the 5
      enolpyruvylshikimate-3-phosphate to chorismate. Here, we report the
      crystallographic structure of CS from Mycobacterium tuberculosis (MtCS) at 2.65 A
      resolution. The MtCS structure is similar to other CS structures, presenting beta
      alpha-beta sandwich structural topology, in which each monomer of MtCS consists
      of a central helical core. The MtCS can be described as a tetramer formed by a
      dimer of dimers. However, analytical ultracentrifugation studies suggest the MtCS
      is a dimer with a more asymmetric shape than observed on the crystallographic
      dimer and the existence of a low equilibrium between dimer and tetramer. Our
      results suggest that the MtCS oligomerization is concentration dependent and some
      conformational changes must be involved on that event.

PMID- 16459103
TI  - Adaptation of gait initiation in children with unilateral idiopathic clubfoot
      following conservative treatment.
AB  - Children with unilateral clubfoot (CF) treated conservatively have residual foot
      deformities and triceps surae m. atrophy. Using surface electromyography of
      tibialis anterior (TA), gastrocnemius (GA), and peroneus longus muscles,
      simultaneously with ground reaction forces recordings, the present work assesses
      the influence of this pathology on the gait initiation process. Ten children with
      CF and 10 healthy children were investigated. In children with CF, the velocity
      of the centre of gravity (CG) at the end of gait initiation did not differ from
      that of healthy children, because of adaptations of anticipation and execution
      phases. CG velocity at the end of anticipation was lower in children with CF than
      in healthy children when the swing foot was the affected one, indicating that
      propulsion was less efficient in this condition. It is shown that this resulted
      from alterations in anticipation duration, initial centre of pressure position
      and TA and PL excitations. Execution was shortened when support was provided by
      the pathological foot: the motor program was adapted to shorten the phase during
      which equilibrium control might be deficient. Biomechanical characteristics of
      the execution phase of children with CF did not depend on the swing foot. This
      indicated that the sound foot cannot be used as a control for accessing residual
      deficiencies.

PMID- 16459104
TI  - Brain hemodynamic changes mediated by dopamine receptors: Role of the cerebral
      microvasculature in dopamine-mediated neurovascular coupling.
AB  - The coupling between neurotransmitter-induced changes in neuronal activity and
      the resultant hemodynamic response is central to the interpretation of
      neuroimaging techniques. In the present study, MRI experiments showed that
      dopamine transporter blockers such as cocaine and dopamine releasers such as
      amphetamine and D1 receptor agonists induced large positive increases in relative
      cerebral blood volume (rCBV) that were not sensitive to nitric oxide synthase
      inhibition. However, D1/D5 receptor antagonism with SCH-23390 prevented or
      blocked the hemodynamic response without any concomitant effect on dopamine
      release. Dopamine D2/D3 receptor agonists, in contrast, induced negative changes
      in rCBV in brain regions corresponding largely to those endowed with these
      receptors. D1 and D5 receptor mRNAs were expressed in microvessels of responsive
      brain areas, while D2 and D3 receptors were not consistently associated with the
      microvascular bed. D3 receptors had an astroglial localization. Together, these
      experiments show that direct effects of dopamine upon the vasculature cannot be
      ignored in measuring the hemodynamic coupling associated with dopaminergic drugs.
      These results further suggest that this coupling is partially mediated through
      D1/D5 receptors on the microvasculature leading to increased rCBV and through
      astroglial D3 receptors leading to decreased rCBV. These data provide additional
      support for the role of local post-synaptic events in neurovascular coupling and
      emphasize that the interpretation of fMRI signals exclusively in terms of
      neuronal activity may be incomplete.

PMID- 16459105
TI  - Recognition memory is modulated by visual similarity.
AB  - We used event-related fMRI to test whether recognition memory depends on visual
      similarity between familiar prototypes and novel exemplars. Subjects memorized
      portraits, landscapes, and abstract compositions by six painters with a unique
      style, and later performed a memory recognition task. The prototypes were
      presented with new exemplars that were either visually similar or dissimilar.
      Behaviorally, novel, dissimilar items were detected faster and more accurately.
      We found activation in a distributed cortical network that included face- and
      object-selective regions in the visual cortex, where familiar prototypes evoked
      stronger responses than new exemplars; attention-related regions in parietal
      cortex, where responses elicited by new exemplars were reduced with decreased
      similarity to the prototypes; and the hippocampus and memory-related regions in
      parietal and prefrontal cortices, where stronger responses were evoked by the
      dissimilar exemplars. Our findings suggest that recognition memory is mediated by
      classification of novel exemplars as a match or a mismatch, based on their visual
      similarity to familiar prototypes.

PMID- 16459106
TI  - Restored speech comprehension linked to activity in left inferior prefrontal and
      right temporal cortices in postlingual deafness.
AB  - The left inferior prefrontal cortex (LIPC) is involved in speech comprehension by
      people who hear normally. In contrast, functional brain mapping has not revealed
      incremental activity in this region when users of cochlear implants comprehend
      speech without silent repetition. Functional brain maps identify significant
      changes of activity by comparing an active brain state with a presumed baseline
      condition. It is possible that cochlear implant users recruited alternative
      neuronal resources to the task in previous studies, but, in principle, it is also
      possible that an aberrant baseline condition masked the functional increase. To
      distinguish between the two possibilities, we tested the hypothesis that activity
      in the LIPC characterizes high speech comprehension in postlingually deaf CI
      users. We measured cerebral blood flow changes with positron emission tomography
      (PET) in CI users who listened passively to a range of speech and non-speech
      stimuli. The pattern of activation varied with the stimulus in users with high
      speech comprehension, unlike users with low speech comprehension. The high
      comprehension group increased the activity in prefrontal and temporal regions of
      the cerebral cortex and in the right cerebellum. In these subjects, single words
      and speech raised activity in the LIPC, as well as in left and right temporal
      regions, both anterior and posterior, known to be activated in speech recognition
      and complex phoneme analysis in normal hearing. In subjects with low speech
      comprehension, sites of increased activity were observed only in the temporal
      lobes. We conclude that increased activity in areas of the LIPC and right
      temporal lobe is involved in speech comprehension after cochlear implantation.

PMID- 16459108
TI  - Neuromagnetic SII responses do not fully reflect pain scale.
AB  - To elucidate the role of somatosensory cortices in coding pain magnitude, we
      recorded the neuromagnetic responses of ten subjects to mild, moderate, and
      severe pain stimulation by delivering thulium-laser pulses on the dorsum of the
      left hand. The stimulus intensities for producing different pain levels were
      determined individually, and the mean values across subjects were 255, 365, and
      490 mJ for mild, moderate, and severe pain, respectively. We obtained 40
      responses for each intensity condition, and analyzed the averaged cortical
      signals by multi-dipole modeling. All subjects showed consistent activation over
      the bilateral secondary somatosensory (SII) cortices for each intensity level,
      peaking around 150-230 ms, with 15-ms earlier on the contralateral hemisphere.
      The SII dipole strength was significantly larger for the moderate than for the
      mild pain stimulation, but lacked further increase as the pain magnitude elevated
      to the severe level. In contrast, the primary somatosensory cortical response was
      detected in only half of our subjects, and thus it seemed difficult to evaluate
      its role in pain intensity coding. Our results suggest that activation strength
      in human SII cortices reflects the magnitude of peripheral noxious inputs only up
      to the moderate level, and some other cerebral correlates may get involved in
      sensing a further increment of pain magnitude.

PMID- 16459107
TI  - Acute opioid effects on human brain as revealed by functional magnetic resonance
      imaging.
AB  - Functional magnetic resonance imaging has been widely used to study brain
      activation induced either by specific sensory stimulation or motor or cognitive
      task performance. We demonstrate that functional magnetic resonance imaging can
      provide information of brain regions involved in opioid-induced central nervous
      system effects. The reproducibility of the responses in the predefined regions of
      interest was confirmed by repeated boluses of ultra-short acting mu-opioid
      receptor agonist remifentanil and saline. We report spatially and temporally
      detailed information after remifentanil administration. Areas rich in mu-opioid
      receptors showed strong activations, whereas primary somatosensory cortex that
      has the lowest density of mu-opioid receptors showed negligible activation. The
      cingulate, orbitofrontal, posterior parietal and insular cortices, and amygdala
      showed activation, which was temporally closely related to most subjective
      sensations that were strongest at 80 to 90 s after drug administration. These
      areas belong to a circuitry that modulates the affective experience of sensory
      stimuli.

PMID- 16459109
TI  - Quality of life in patients with chronic type B aortic dissection.
AB  - OBJECTIVE: To study functioning and well-being among patients with conservatively
      treated acute type B aortic dissection. DESIGN: Cross-sectional survey. METHODS:
      Patients referred with acute type B dissection between January 1990 and November
      2000 were prospectively followed after conservative initial management. In
      October 2002, we sent the SWED-QUAL questionnaire to all patients who were alive
      and had not undergone surgery of the dissected aorta. Fifty-three of 55 patients
      responded, 39 males and 14 females. Patient scores for the 12 aspects of health
      related quality of life included in the SWED-QUAL were compared to a normative
      Swedish population, controlled for age and gender differences. RESULTS: There
      were only minor differences in functioning and well-being between patients and
      the normative population. Patients reported similar emotional well-being,
      cognitive functioning, quality of sleep, overall general health and quality of
      social relations as their normative counterparts. However, patients' perception
      of their current health, prior health, perceived resistance to illness and health
      concern was worse than in the normative population. Female patients also reported
      worse physical functioning and a lower satisfaction with their physical
      functioning than male patients or female counterparts in the normative
      population. We did not find any significant association between length of follow
      up and quality of life scores. CONCLUSIONS: In terms of functioning and well
      being, patients with uncomplicated acute type B aortic dissection, who are
      initially managed conservatively, differ little from a normative Swedish
      population. Our study supports conservative management of this group of patients.

PMID- 16459110
TI  - Neuropsychological morbidity linked to childhood sleep-disordered breathing.
AB  - Understanding the long-term neuropsychological consequences of sleep disorders in
      children poses a significant challenge to researchers. Since children are in a
      state of rapidly changing cognition and neurobehavioral function, impacts on
      development may have profound consequences. Recent studies now demonstrate that
      mild sleep apnea and snoring, once considered within the spectrum of normal sleep
      patterns, are associated with deficits of neuropsychological function.
      Preliminary data suggest that some of these cognitive deficits may be reversible
      following treatment of mild sleep apnea in children; however, factors such as age
      at treatment, duration of sleep disordered breathing, pre-morbid intellectual
      level, socioeconomic status, or the effectiveness of treatment may adversely
      affect long-term outcome. Furthermore, it is imperative that researchers
      determine whether the developing brain exhibits critical periods of plasticity
      during which episodes of sleep-disordered breathing might cause long-term or
      permanent neuropsychological effects.

PMID- 16459111
TI  - Blue eye disease porcine rubulavirus (PoRv) infects pig neurons and glial cells
      using sialo-glycoprotein as receptor.
AB  - Pig neural cells express glycoproteins with sialylated N-linked oligosaccharide
      chains (SNOC) which are used by the porcine rubulavirus (PoRv) as receptors. Pig
      neuronal or glial cell cultures were employed to investigate (a) whether PoRv
      infects such cells using a molecule expressing SNOC, and (b) the role of viral
      envelope glycoproteins in establishing the infection. Enriched neuronal or glial
      cell cultures were exposed to PoRv and infection was detected
      immunocytochemically. Neuronal cultures prepared from neonatal pigs were treated
      enzymatically to eliminate sialic acid or N-linked oligosaccharide chains.
      Primary neural cultures were exposed to anti-HN or anti-F preincubated with PoRv
      to study the role of the viral glycoproteins. In enriched cultures, PoRv infected
      neurons and glial cells, and sialic acid expressed in N-linked oligosaccharide
      chains appeared to play a central role in infection. It was concluded that HN and
      F viral glycoproteins are required to infect neurons and glial cells.

PMID- 16459112
TI  - Measurement of serum interleukin-10 in the dog.
AB  - The objective was to evaluate independently the reliability of a commercially
      available canine serum interleukin-10 (IL-10) enzyme-linked immunoassay (ELISA)
      and to investigate canine serum IL-10 concentrations in healthy dogs, in dogs
      with a naturally-occurring acute phase reaction and in dogs following surgical
      stimulus by assessing intra- and interassay imprecision, inaccuracy and detection
      limits. Median (and range) serum IL-10 concentrations (ng/L) in the various
      groups were as follows: healthy dogs (n=15), 18.9 (11.2-71.5); dogs with pyometra
      (n=9), 37.9 (12.4-201.8); dogs with angiostrongylosis (n=8), 20.29 (14.3-108.7)
      and values in dogs following surgical stimulus (n=15), 14.8 (10.7-65.8). The
      assay measured canine serum IL-10 reliably (intra- and interassay imprecision 4.9
      8.3% and 9.9-10.9%, respectively; detection limit 10.7 ng/L with no significant
      inaccuracy). No significant increases in IL-10 were observed following surgical
      stimulus and no difference in IL-10 was observed between the diagnostic groups.
      IL-10 values showed a higher degree of variation in dogs with an inflammatory
      response, i.e. those with elevated serum C-reactive protein (CRP) concentrations,
      compared to healthy dogs. As anticipated, healthy dogs had low levels of both
      analytes, whereas dogs with an acute phase response had IL-10 levels with no
      clear relationship to CRP concentrations, with observed low IL-10 values even
      when there was a marked inflammatory response.

PMID- 16459113
TI  - Epidemiology of porcine non-specific colitis on Scottish farms.
AB  - The objective of this study was to investigate epidemiological risk factors for
      porcine non-specific colitis (NSC). Forty-seven Scottish pig farms, with and
      without a clinical history of diarrhoea during the growing period (15-40 kg),
      were selected. The study included farm visits, clinical inspection of pigs,
      completion of farm management questionnaires, pathological tests into the cause
      of the diarrhoea and analysis of the non-starch polysaccharide (NSP) content of
      feeds. The results from 17 farms designated as NSC and 10 control farms suggest
      dietary associations with NSC. Farms with NSC fed diets with significantly higher
      levels of NSPs, especially containing the sugars glucose, arabinose and xylose.
      Few management factors were identified, although the high prevalence of
      infectious colitis reduced the power of the study.

PMID- 16459114
TI  - Determination of sample temperature and temperature stability with 129Xe NMR.
AB  - The (129)Xe chemical shift of xenon dissolved in isotropic liquids is very
      sensitive to solvent density, which in turn is dependent on the sample
      temperature. Therefore, the (129)Xe chemical shift can be used as the basis of a
      thermometer for measuring actual sample temperatures in NMR experiments. Good
      accuracy can be achieved, but the thermometer is particularly useful in
      monitoring temperature stability. In the present case, carbon tetrachloride
      (CCl(4)), ethylbromide (C(2)H(5)Br), and deuterated chloroform (CDCl(3)) were
      chosen as solvents because of their large thermal expansion coefficient.

PMID- 16459115
TI  - Homogeneous broadenings in 2D solid-state NMR of half-integer quadrupolar nuclei.
AB  - The question of the homogeneous broadening that occurs in 2D solid-state NMR
      experiments is examined. This homogeneous broadening is mathematically introduced
      in a simple way, versus the irreversible decay rates related to the coherences
      that are involved during t1 and t2. We give the pulse sequences and coherence
      transfer pathways that are used to measure these decay rates. On AlPO4 berlinite,
      we have measured the 27Al echo-type relaxation times of the central and satellite
      transitions on 1Q levels, so that of coherences that are situated on 2Q, 3Q, and
      5Q levels. We compare the broadenings that can be deduced from these relaxation
      times to those directly observed on the isotropic projection of berlinite with
      multiple-quantum magic-angle spinning (MAS), or satellite-transition MAS. We show
      that the choice of the high-resolution method, should be done according to the
      spin value and the corresponding homogeneous broadening.

PMID- 16459116
TI  - Dietary macronutrients influence 13C and 15N signatures of pinnipeds: captive
      feeding studies with harbor seals (Phoca vitulina).
AB  - Metabolic effects of dietary macronutrients on diet-tissue isotopic
      discrimination factors were investigated in harbor seals. Three seals were fed
      either high fat/low protein herring (H), or low fat/high protein pollock (P), and
      switched to the alternative every 4 months. This allowed each seal to be
      subjected to two dietary treatments in each of three metabolically defined
      seasons (breeding from May to September, molting from September to January, and
      late winter/early spring period from January to May) over a 2 year cycle, and
      function as its internal control regardless of physiological changes over season.
      One seal was fed a constant equal mix of H and P over the entire trial. Up to 1
      per thousand differences in serum delta15N values of one seal fed alternatively
      on H and P were observed. Progressively more enriched serum delta15N values as
      diet switching from H to P might link to changes in seal digestive physiology and
      protein metabolism in response to very high protein intake on P diet. These
      findings demonstrate that dietary macronutrients of prey species and protein
      intake level of consumers also play important roles in shaping isotopic patterns
      of a consumer's tissues, and thus influence accurate data interpretation of
      stable isotope techniques in ecological applications.

PMID- 16459117
TI  - Short-term effects of hyposmotic shock on Na+/K+ -ATPase expression in gills of
      the euryhaline milkfish, Chanos chanos.
AB  - Changes in expression of gill Na+/K+ -ATPase (NKA) on a short-term (96 h) time
      course following hyposmotic shock (direct transfer to fresh water) of the
      euryhaline, marine milkfish were studied on gene, protein, and cell levels in
      this paper. Plasma osmolality and [Na+] responded with rapid declines in 3 h post
      transfer yet, thereafter, remained constant. Plasma [Cl-] gradually fell to a
      significantly lower level at 6 h post-transfer. Gills responded to hyposmotic
      shock by a dual phase enhancement of NKA activity and protein abundance; (a)
      Before 24 h: NKA activity increased as early as 3 h and reached a maximum level
      from 6 to 12 h post-transfer coincided with the sustained lower levels of plasma
      osmolality, [Na+], and [Cl-] since 3 h post-transfer. This was followed by a
      gradual rise in alpha-subunit protein levels that peaked at 12 h post-transfer.
      Meanwhile, alpha-mRNA of NKA did no show significant change. (b) After 24 h: NKA
      activity as well as the amounts of alpha-subunit mRNA and protein increased
      significantly. Direct freshwater transfer induced a prompt and significant
      decrease of NKA immunoreactive (NKIR) cell abundance in filaments before 24 h,
      followed by a significant increase after 24 h due to their development in
      filaments and lamellae. Increased number of NKIR cells after 24 h of hyposmotic
      shock may occur in conjunction with rise of NKA activity as well as alpha-subunit
      mRNA and protein abundance. In conclusion, milkfish is able to avoid an excessive
      drop in plasma ions immediately upon hyposmotic shock and maintain plasma ions on
      a marginal lower level in fresh water. Notably, the initial increase in NKA
      activity (adjustive phase; 3-12 h) and delayed increase in NKA mRNA and protein
      abundance (regulatory phase; 48-96 h) indicate the importance of a higher level
      of the gill enzyme in milkfish upon hyposmotic shock.

PMID- 16459118
TI  - Plasma lactate and glucose flushes following burst swimming in silver trevally
      (Pseudocaranx dentex: Carangidae) support the "releaser" hypothesis.
AB  - Silver trevally (Pseudocaranx dentex) are highly athletic marine teleosts
      inhabiting the tropical waters of the Great Barrier Reef, Australia. Burst
      swimming increased plasma lactate from 1.6 +/- 0.4 S.D. to 21.6 +/- 3.3 mM (N =
      6), among the highest values reported for functional hypoxia in fish. These data
      support the hypothesis that elite swimmers release lactate produced in the
      myotome into the circulation following anaerobic burst activity. The fish further
      developed a hyperglycaemic response to burst exercise with plasma glucose
      increasing from 6.6 +/- 2.0 to 13.2 +/- 2.3 mM (N = 6). Post-exercise erythrocyte
      swelling also occurred, but nucleoside triphosphate levels remained unaltered and
      do not provide a mechanism to modulate haemoglobin function during exercise.
      Metabolism of the blood cells appeared to be fuelled by both lactate and glucose.

PMID- 16459119
TI  - Identification and distribution of heparan sulfate proteoglycans in the white
      muscle of Atlantic cod (Gadus morhua) and spotted wolffish (Anarhichas minor).
AB  - Heparan sulfate proteoglycans (HSPGs) were identified in pre-rigor muscle of two
      species of cold water fish, Atlantic cod (Gadus morhua) and spotted wolffish
      (Anarhichas minor) by biochemical and immunological methods. The distribution was
      described by immunohistology. Special emphasis was directed to the extracellular
      matrix (ECM) HSPGs perlecan and agrin. In vivo 35S-sulfate labeling combined with
      ultracentrifugation in CsCl2, DEAE chromatography and scintillation counting of
      the eluates, revealed that the content of 35S-labeled PGs was much higher in
      wolffish than in cod. A considerable proportion of the 35S-sulfated PGs in both
      species was HSPG, as judged by nitrous acid degradation. HSPG represented,
      however, a higher proportion of the 35S-sulfated PGs in cod compared to wolffish.
      Dot blot and electrophoresis/western blot using two different HS-mAbs, 10E4 and
      HepSS-1 indicated structural differences in the HS-chains of the PGs present.
      This observation was strengthened by immunohistochemistry, showing that both mAbs
      detected epitopes in the pericellular area, but the staining patterns were not
      superimposable. Two different agrin isoforms were identified in both species.
      Furthermore, in the white muscle of both cod and wolffish, perlecan mAb (A7L6)
      showed positive staining restricted to the transition between myocommata and
      myofibers.

PMID- 16459120
TI  - Identification of a novel C2 domain factor in ovaries of orange-spotted grouper
      (Epinephelus coioides).
AB  - Follicle consists of an oocyte and a lot of surrounding follicular cells, and
      significant interactions exist between the oocyte and the somatic cells. In this
      study, a novel cDNA has been screened from a subtractive cDNA library between
      tail bud embryos and blastula embryos in the protogynous hermaphrodite orange
      spotted grouper (Epinephelus coioides). Its full-length cDNA is 821 bp, and has
      an ORF of 414 bp for encoding a peptide of 137 aa, which shows 38%, 37%, 33%, and
      33% homology with 4 putative proteins screened from zebrafish (Danio rerio).
      Conserved domain search in NCBI reveals a single C2 domain existing in the C2
      domain superfamily proteins, and has only 7 beta strands in comparison with 8
      beta strands of C2 domains in other C2 domain superfamily proteins. Artificial
      sex reversal, RT-PCR analysis and Western blot detection demonstrated ovary
      specific expression of the C2 domain factor, and therefore the novel gene was
      designated as E. coioides ovary-specific C2 domain factor, EcOC2 factor.
      Moreover, predominant expression of EcOC2 factor was further revealed in grouper
      mature ovary, and its strong immunofluorescence signals were located between
      granulosa cells and oocyte zona radiata in grouper mature follicles. The data
      indicate that the novel EcOC2 factor might be a main component that associates
      between granulosa cells and the oocyte during oocyte maturation, and might play
      significant roles in regulating oocyte maturation and ovulation. Further studies
      on its developmental behaviour and physiological functions will elucidate the
      interactions between oocyte and the surrounding somatic cells and the underlying
      molecular mechanisms.

PMID- 16459121
TI  - A familial missense mutation in the hinge region of DAX1 associated with late
      onset AHC in a prepubertal female.
AB  - Mutations in the DAX1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita
      (AHC) critical region on the X chromosome gene 1; NR0B1) cause X-linked AHC, a
      disease characterized by primary adrenal failure in infancy and hypogonadotropic
      hypogonadism. All known missense mutations impair DAX1 repression of
      steroidogenic factor 1 (SF1) transactivation and have been localized to the
      putative ligand binding domain. Here, an asymptomatic father and his late-onset
      AHC daughter were both shown to share a novel DAX1 mutation (C200W), the first
      missense mutation identified in the hinge region of DAX1. Using
      immunohistochemistry we demonstrate that the sub-cellular localization of the
      C200W mutant DAX1 protein is shifted from the nucleus to the cytoplasm. The
      disturbed localization of the C200W mutant in transfected cells correlates with
      impaired transcriptional repression activity. The import defect is relatively
      mild, retaining 80% of wild-type activity, which may explain the unusually mild
      phenotype. Import of DAX1 into the nucleus involves a direct interaction with
      SF1. In vitro assays demonstrate that the C200W mutant retains the ability to
      functionally interact with SF1, which suggests that SF1-independent interactions
      of DAX1 could be responsible for the import defect.

PMID- 16459122
TI  - Increased tremor severity in bilineal essential tremor: a report of two families.
AB  - Up to 6% of the general population have essential tremor (ET). In a number of
      couples both partners may have ET. The clinical profile of ET in children and the
      parents where both parents and the child have ET remains to be established. We
      report on two families where both parents and one child have ET. The severity of
      ET was greater in the children than in either parent. Such families could provide
      special opportunity to determine relation between genotype and phenotypic
      expression of ET.

PMID- 16459123
TI  - Reversible Parkinsonian syndrome associated with anti-neuronal antibodies in
      acute EBV encephalitis: a case report.
AB  - We report a case of subacute-onset isolated parkinsonian syndrome in a 16 years
      old patient. Epstein-Barr infection was diagnosed according to serologic
      evidences. Parkinson-like syndrome completely recovered after 60 days.
      Autoantibodies reacting against a 130 Kda antigens expressed in human
      neuroblastoma cell line were detected. Pathogenesis and differential diagnosis
      are briefly discussed. EBV testing could be worthwhile in juvenile, acute-onset,
      parkinsonism.

PMID- 16459124
TI  - Evaluation of the effect of training using auditory stimulation on rhythmic
      movement in Parkinsonian patients--a combined motor and [18F]-FDG PET study.
AB  - INTRODUCTION: A programme of rehabilitation using auditory cues has previously
      been shown to decrease movement variability in the gait of Parkinsonian patients.
      OBJECTIVE AND METHODS: We studied the temporal variability of finger-tapping and
      gait in 9 patients with Parkinson's disease (PD) before and after they undertook
      a physical rehabilitation programme. Positron Emission Tomography (PET) using 2
      deoxy-2[(18)F]fluoro-D-glucose (FDG) was performed in these subjects to look for
      changes in metabolic brain activity after completion of the rehabilitation
      program. RESULTS: The reduction of variability was seen not only in gait but also
      other repetitive movements such as finger tapping. Furthermore, here we show
      differences in resting regional cerebral glucose utilisation in these patients
      compared to healthy controls (significant hypometabolism-p < 0.001-for the PD
      group in the right parietal and temporal lobes, left temporal and frontal lobes
      and a hypermetabolism in the left cerebellum) and specific changes following the
      improvements in repetitive movement abilities (significant metabolic increment-p
      < 0.001-in the PD group in the right cerebellum and in the right parietal and
      temporal lobes). CONCLUSIONS: Although our study does not allow us to draw firm
      conclusions, it provides new information on the neural basis of auditory
      stimulation in PD. Our results extend those from previous studies to show
      improvement in the temporal variability of two types of rhythmic movements after
      participation by PD patients in a physical rehabilitation programme, along with
      changes in glucose uptake in several brain areas involved in sensorimotor
      processing.

PMID- 16459125
TI  - Amyotrophic lateral sclerosis in an Italian professional soccer player.
AB  - Amyotrophic lateral sclerosis (ALS) is a rare devastating neurodegenerative
      disease of unknown etiology. Two recent epidemiological studies showed a high
      risk for ALS among Italian male soccer players. We present the clinical and
      occupational history of an Italian professional soccer player affected by
      sporadic ALS. The early onset of ALS (45 years), the bulbar form, the playing
      position (midfielder) and the duration of the job as professional soccer (17
      years) are four characteristics of this patient that are in good agreement with
      the findings in the previous epidemiological studies. This patient reports the
      frequent consumption of fructose 1,6 biphosphate, extracts of suprarenal cortex,
      crotetamide and cropropamide, and dietary supplements (branched chain amino acids
      and creatine) during his playing career. Some hypotheses have been proposed to
      explain this high excess of deaths for ALS among soccer players: (a) vigorous
      physical activity; (b) soccer specific trauma or microtrauma; (c) use of illegal
      toxic substances or chronic misuse of drugs (most often anti-inflammatory) and
      dietary supplements; and (d) exposure to pesticides used on playing fields. The
      overall available clinical and epidemiological evidence supports the possible
      relation between the specific occupational environment (soccer) and the
      occurrence of ALS in this patient.

PMID- 16459126
TI  - Allelic variation of a functional polymorphism in the serotonin transporter gene
      and depression in Parkinson's disease.
AB  - A genetic susceptibility to depression in PD, acting via the serotonergic system,
      has been suggested. We examined the influence of allelic variation (L/S) in a
      functional polymorphism in the serotonin transporter (5-HTTLPR) gene upon mood in
      108 PD patients and 82 controls. Using a logistic regression model we found no
      evidence for an association between 5-HTTLPR genotypes, or the presence of the S
      allele, and depression.

PMID- 16459127
TI  - Role of islet amyloid in type 2 diabetes mellitus.
AB  - Diabetes mellitus is one of the most common metabolic diseases worldwide and its
      prevalence is rapidly increasing. Due to its chronic nature (diabetes mellitus
      can be treated but as yet not cured) and its serious complications, it is one of
      the most expensive diseases with regard to total health care costs per patient.
      The elevated blood glucose levels in diabetes mellitus are caused by a defect in
      production and/or secretion of the polypeptide hormone insulin, which normally
      promotes glucose-uptake in cells. Insulin is produced by the pancreatic 'beta
      cells' in the 'islets of Langerhans', which lie distributed within the exocrine
      pancreatic tissue. In type 2 diabetes mellitus, the initial defect in the
      pathogenesis of the disease in most of the patients is believed to be 'insulin
      resistance'. Hyperglycemia (clinically overt diabetes mellitus) will not develop
      as long as the body is able to produce enough insulin to compensate for the
      reduced insulin action. When this compensation fails ('beta-cell failure') blood
      glucose levels will become too high. In this review, we discuss one of the
      mechanisms that have been implicated in the development of beta-cell failure,
      i.e. amyloid formation in the pancreatic islets. This islet amyloid is a
      characteristic histopathological feature of type 2 diabetes mellitus and both in
      vitro and in vivo studies have revealed that its formation causes death of islet
      beta-cells. Being a common pathogenic factor in an otherwise heterogeneous
      disease, islet amyloidosis is an attractive novel target for therapeutic
      intervention in type 2 diabetes mellitus.

PMID- 16459128
TI  - Molecular and functional diversity of maize.
AB  - Over the past 10,000 years, man has used the rich genetic diversity of the maize
      genome as the raw material for domestication and subsequent crop improvement.
      Recent research efforts have made tremendous strides toward characterizing this
      diversity: structural diversity appears to be largely mediated by helitron
      transposable elements, patterns of diversity are yielding insights into the
      number and type of genes involved in maize domestication and improvement, and
      functional diversity experiments are leading to allele mining for future crop
      improvement. The development of genome sequence and germplasm resources are
      likely to further accelerate this progress.

PMID- 16459129
TI  - The maize genome as a model for efficient sequence analysis of large plant
      genomes.
AB  - The genomes of flowering plants vary in size from about 0.1 to over 100 gigabase
      pairs (Gbp), mostly because of polyploidy and variation in the abundance of
      repetitive elements in intergenic regions. High-quality sequences of the
      relatively small genomes of Arabidopsis (0.14 Gbp) and rice (0.4 Gbp) have now
      been largely completed. The sequencing of plant genomes that have a more
      representative size (the mean for flowering plant genomes is 5.6 Gbp) has been
      seen as a daunting task, partly because of their size and partly because of the
      numerous highly conserved repeats. Nevertheless, creative strategies and powerful
      new tools have been generated recently in the plant genetics community, so that
      sequencing large plant genomes is now a realistic possibility. Maize (2.4-2.7
      Gbp) will be the first gigabase-size plant genome to be sequenced using these
      novel approaches. Pilot studies on maize indicate that the new gene-enrichment,
      gene-finishing and gene-orientation technologies are efficient, robust and
      comprehensive. These strategies will succeed in sequencing the gene-space of
      large genome plants, and in locating all of these genes and adjacent sequences on
      the genetic and physical maps.

PMID- 16459130
TI  - Organization and variability of the maize genome.
AB  - With a size approximating that of the human genome, the maize genome is about to
      become the largest plant genome yet sequenced. Contributing to that size are a
      whole-genome duplication event and a retrotransposition explosion that produced a
      large amount of repetitive DNA. This DNA is greatly under-represented in cDNA
      collections, so analysis of the maize transcriptome has been an expedient way of
      assessing the gene content of maize. Over 2 million maize cDNA sequences are now
      available, making maize the third most widely studied organism, behind mouse and
      man. To date, the sequencing of large-sized DNA clones has been largely driven by
      the genetic interests of different investigators. The recent construction of a
      physical map that is anchored to the genetic map will aid immensely in the maize
      genome-sequencing effort. However, studies showing that the repetitive DNA
      component is highly polymorphic among maize inbred lines point to the need to
      sample vertically a few specific regions of the genome to evaluate the extent and
      importance of this variability.

PMID- 16459131
TI  - Novel paralogous gene families with potential function in legume nodules and
      seeds.
AB  - Within the plant kingdom, legumes are unusual in their ability to form nitrogen
      fixing nodules in symbiosis with certain bacteria in the family Rhizobiaceae
      (rhizhobia). Genes that are required for signaling between plant and symbiont,
      and for the development and maintenance of the nodule, were either created de
      novo or adopted from other plant pathways. Only in recent years have genome-scale
      sequence data from legumes made it possible to identify large, novel families of
      genes probably evolved to function in nodulation. Members of these novel families
      are expressed in seeds or nodules, and are homologous to defense-related
      proteins. Perhaps the most striking example is a large family (of more than 340
      members) of cysteine cluster proteins that have homology to plant defensins.

PMID- 16459132
TI  - Differential gene expression of pathogens inside infected hosts.
AB  - DNA microarray is a useful technology for studying differential gene expression
      in the context of microbe-host interactions. This review concentrates on recent
      findings of the survival strategies of three intracellular pathogens: Shigella
      flexneri, Salmonella enterica serovar Typhimurium and Mycobacterium tuberculosis.

PMID- 16459133
TI  - Tandemly repeated DNA sequence instabilities induced by two promoters of
      morphological transformation in vitro: a short-term response to non-mutagenic
      agents in C3H/10T1/2 cells.
AB  - The ability of tumour promoters to alter DNA stability within regions that
      contain tandemly repeated sequences (TRSs), was studied in a cell culture model
      of multi-stage carcinogenesis. Non-cytotoxic concentrations of TPA (12-O
      tetradecanoyl-phorbol-13-acetate) and xanthine oxidase with xanthine substrate,
      sufficient to promote morphological transformation in C3H/10T1/2 cultures, were
      tested for their effects on mutation frequencies in TRSs by a DNA fingerprinting
      approach. Specifically, restriction digests of genomic DNA samples from randomly
      selected, non-transformed clones, isolated from cultures after several days
      exposure to promoters, were visualized by Southern hybridizations with the multi
      locus pentamer repeat sequence probe, Ms6-Hm (Pc-1). Basal and promoter-induced
      frequencies of sub-clone TRS fingerprint polymorphisms were estimated in five
      cell populations: an uncloned stock culture, three populations established from
      normal-appearing sub-clones, and one clonal population established from a 3
      methylcholanthrene (MCA)-transformed focus. Basal variant fingerprint frequencies
      spanned a range from 0.0 to 0.43% mutants/band among cells from the four
      untransformed populations. Both TPA and xanthine oxidase treatments significantly
      increased recorded mutation frequencies, 2.3- and 2.7-fold, respectively, using
      combined data from the progenitor population and three untransformed clones. The
      untreated MCA-transformed clonal population appeared to contain a single, pre
      existing mutant restriction fragment, but additional mutations were induced
      thereafter, in response to the promoting treatments. Taken together, the measured
      increases in mutations were highly significant and suggest that promoters of cell
      transformation in the C3H/10T1/2 cell line might induce a genome-wide instability
      targeted to regions containing Ms6-Hm sequence motifs.

PMID- 16459134
TI  - Involvement of the Na+/H+ exchanger in membrane phosphatidylserine exposure
      during human platelet activation.
AB  - Platelet membrane phosphatidylserine (PS) exposure that regulates the production
      of thrombin represents an important link between platelet activation and the
      coagulation cascade. Here, we have evaluated the involvement of the Na+/H+
      exchanger (NHE) in this process in human platelets. PS exposure induced in human
      platelets by thrombin, TRAP, collagen or TRAP+ collagen was abolished in a Na+ 
      free medium. Inhibition of the Na+/H+ exchanger (NHE) by 5-(N-Ethyl-N-Isopropyl)
      Amiloride (EIPA) reduced significantly PS exposure, whereas monensin or
      nigericin, which mimic or cause activation of NHE, respectively, reproduced the
      agonist effect. These data suggest a role for Na+ influx through NHE activation
      in the mechanism of PS exposure. This newly identified pathway does not discount
      a role for Ca2+, whose cytosolic concentration varies together with that of Na+
      after agonist stimulation. Ca2+ deprivation from the incubation medium only
      attenuated PS exposure induced by thrombin, measured from the uptake of FM1-43 (a
      marker of phospholipid scrambling independent of external Ca2+). Surprisingly,
      removal of external Ca2+ partially reduced FM1-43 uptake induced by A23187, known
      as a Ca2+ ionophore. The residual effect can be attributed to an increase in
      [Na+]i mediated by the ionophore due to a lack of its specificity. Finally,
      phosphatidylinositol 4,5-bisphosphate (PIP2), previously reported as a target for
      Ca2+ in the induction of phospholipid scrambling, was involved in PS exposure
      through a regulation of NHE activity. All these results would indicate that the
      mechanism that results in PS exposure uses redundant pathways inextricably linked
      to the physio-pathological requirements of this process.

PMID- 16459135
TI  - Intact acute cardiorenal and humoral responsiveness following chronic
      subcutaneous administration of the cardiac peptide BNP in experimental heart
      failure.
AB  - BACKGROUND: BNP is a cardiac peptide with vasodilating, lusitropic and
      natriuretic properties mediated by the second messenger cGMP. We have previously
      shown that chronic subcutaneous (SQ) administration of BNP in experimental CHF
      resulted in improved haemodynamics and unloading of the heart. However, it is
      unknown if this will lead to the development of tolerance to exogenous BNP.
      METHODS: The current study extends our previous study and compares the
      cardiorenal effects of acute administration of SQ BNP (5 microg/kg) in a group of
      dogs (n = 5) with rapid ventricular pacing induced CHF (180 bpm for 10 days) to a
      separate group of CHF dogs (n = 6), who received chronic SQ BNP (5 microg/kg)
      three times a day for 10 days. RESULTS: Acute administration of SQ BNP resulted
      in similar increases in both plasma cGMP (35+/-5 vs. 29+/-2 pmol/ml) and urinary
      cGMP excretion (UcGMPV) (6000+/-1000 vs. 4000+/-600 pmol/min) in both the Chronic
      SQ BNP treated and the Untreated CHF groups (P > 0.05). These were associated
      with decreased cardiac filling pressures and increased urine flow, which were
      also similar in both groups. CONCLUSION: In experimental CHF, chronic SQ BNP
      administration did not result in the development of tolerance as demonstrated by
      increases in both plasma cGMP and UcGMPV following acute administration of SQ
      BNP. This may have important clinical implications, suggesting that chronic BNP
      administration does not lead to the development of tolerance to acute BNP
      administration.

PMID- 16459136
TI  - The official World Association of Sleep Medicine (WASM) standards for recording
      and scoring periodic leg movements in sleep (PLMS) and wakefulness (PLMW)
      developed in collaboration with a task force from the International Restless Legs
      Syndrome Study Group (IRLSSG).

PMID- 16459137
TI  - The eye in sleep apnea syndrome.
AB  - Sleep apnea syndrome (SAS) is a disease characterized by recurrent complete or
      partial upper airway obstructions during sleep. The majority of patients with SAS
      demonstrate this obstruction either at the nasopharynx or the oropharynx. Risk
      factors for SAS include obesity, male gender, upper airway abnormalities, alcohol
      use, snoring, and neck girth of more than 17 in. in men or 16 in. in women.
      Reported ophthalmic findings in patients with SAS include floppy eyelid syndrome
      (FES), glaucoma, and non-arteritic anterior ischemic optic neuropathy (NAION).

PMID- 16459138
TI  - Caffeine challenge in insomniac patients after total sleep deprivation.
AB  - BACKGROUND AND PURPOSE: This study compared the effects of caffeine in patients
      with primary insomnia and normal volunteers. The main goal was to determine the
      differences in sensitivity to caffeine between the groups. We investigated the
      effects on daytime sleep of placebo or caffeine after a night of total sleep
      deprivation (SD). We hypothesized that insomniacs would be more affected by
      caffeine, which would suggest a change in adenosine receptor (number or
      sensitivity) in primary insomniacs. PATIENTS AND METHODS: Six primary insomnia
      patients (Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) and six
      normal volunteers with no sleep complaints participated in a double-blind study
      with caffeine or placebo administered under a cross-over design with each subject
      serving as his or her own control. The participants did not have a history of
      drinking coffee or caffeinated beverages. Data from all-night polysomnography and
      multiple sleep latency test (MSLT) were collected in the sleep research
      laboratory of National Institute of Medical Sciences and Nutrition Salvador
      Zubiran. RESULTS: During the baseline night, patients with insomnia had
      significantly less delta sleep and less total sleep time than the normal
      volunteers. Mean sleep latency under basal MSLT did not differ between the
      groups. However, insomnia patients had significantly less total sleep during each
      nap compared to normal volunteers. After one night of total SD and under caffeine
      administration, the insomniacs had significantly longer sleep latency and less
      total sleep time in MSLT compared to normal volunteers. After SD, healthy
      volunteers reduced sleep latencies in MSLT with or without caffeine. CONCLUSIONS:
      Patients with insomnia had a higher sensitivity to the diurnal awakening effect
      of caffeine even after one night of SD. This suggests that changes in the
      adenosine receptors could, in part, be responsible for the hyperarousal state
      that has been reported in primary insomnia.

PMID- 16459139
TI  - Sleepwalking, a disorder of NREM sleep instability.
AB  - BACKGROUND AND PURPOSE: Thirty-two chronic sleepwalkers who were part of a
      larger, previously reported sleepwalking group all achieved control of
      sleepwalking after undergoing treatment for an associated sleep disorder. In the
      current study, all records were blindly scored to perform a cyclic alternating
      pattern (CAP) analysis. PATIENTS AND METHODS: Thirty-two young adult chronic
      sleepwalkers had polysomnography (PSG) on initial nights without sleepwalking
      events, as did age-matched normal controls and patients with mild sleep
      disordered breathing (SDB). More than 90% of these patients with mild SDB had
      upper airway resistance syndrome (UARS). Ten randomly selected PSGs for
      sleepwalkers and matched controls also had quantitative electroencephalographic
      (EEG) analysis using Fast Fourier Transformation (FFT) with determination of
      delta power for each non-rapid eye movement (NREM)-REM sleep cycle. RESULTS:
      Compared to normal controls, an investigation of CAP in sleepwalkers demonstrated
      the presence of an abnormal CAP rate with a decrease in phase A1 and an increase
      in phases A2 and A3 on non-sleepwalking nights. The results of CAP analysis in
      sleepwalkers were similar to those obtained in age-matched UARS patients.
      Furthermore, the analysis of the first four NREM-REM sleep cycles reconfirmed the
      presence of an important decrease in delta power in sleep cycles 1 and 2 during a
      non-sleepwalking night in sleepwalkers compared to normal controls. CONCLUSIONS:
      The presence of both 'hypersynchronous slow delta' and 'burst of delta waves'
      have been reported in sleepwalkers, but their significance is controversial.
      These EEG patterns are similar to phase A1 (and possibly A2) of the CAP. Proper
      analysis of the sleep EEG of sleepwalkers should integrate CAP analysis.
      Sleepwalkers on a non-sleepwalking night present instability of NREM sleep, as
      demonstrated by this analysis. This instability is similar to the one noted in
      UARS patients. Subtle sleep disorders associated with chronic sleepwalking
      constitute the unstable NREM sleep background on which sleepwalking events occur.
      A subtle associated sleep disorder should be systematically searched for and
      treated in the presence of sleepwalking with abnormal CAP.

PMID- 16459140
TI  - Epidemiology of insomnia: prevalence, self-help treatments, consultations, and
      determinants of help-seeking behaviors.
AB  - BACKGROUND AND PURPOSE: To estimate the prevalence of insomnia symptoms and
      syndrome in the general population, describe the types of self-help treatments
      and consultations initiated for insomnia, and examine help-seeking determinants.
      PATIENTS AND METHODS: A randomly selected sample of 2001 French-speaking adults
      from the province of Quebec (Canada) responded to a telephone survey about sleep,
      insomnia, and its treatments. RESULTS: Of the total sample, 25.3% were
      dissatisfied with their sleep, 29.9% reported insomnia symptoms, and 9.5% met
      criteria for an insomnia syndrome. Thirteen percent of the respondents had
      consulted a healthcare provider specifically for insomnia in their lifetime, with
      general practitioners being the most frequently consulted. Daytime fatigue (48%),
      psychological distress (40%), and physical discomfort (22%) were the main
      determinants prompting individuals with insomnia to seek treatment. Of the total
      sample, 15% had used at least once herbal/dietary products to facilitate sleep
      and 11% had used prescribed sleep medications in the year preceding the survey.
      Other self-help strategies employed to facilitate sleep included reading,
      listening to music, and relaxation. CONCLUSIONS: These findings confirm the high
      prevalence of insomnia in the general population. While few insomnia sufferers
      seek professional consultations, many individuals initiate self-help treatments,
      particularly when daytime impairments such as fatigue become more noticeable.
      Improved knowledge of the determinants of help-seeking behaviors could guide the
      development of effective public health prevention and intervention programs to
      promote healthy sleep.

PMID- 16459141
TI  - Combined effects of apoE-CI-CII cluster and LDL-R gene polymorphisms on
      chromosome 19 and coronary artery disease risk.
AB  - OBJECTIVE: To investigate associations of gene polymorphisms of the apoE-CI-CII
      gene cluster and the LDL-R gene on coronary artery disease (CAD) and their
      interactions with alcohol drinking and smoking in the Chinese Han population.
      METHODS: A questionnaire survey of the behaviors of smoking and drinking, dietary
      patterns and anamnesis was conducted among 203 patients of CAD, aged 65.0 +/-
      11.1 years, and 365 controls, aged 63.6 +/- 12.0 years. Peripheral blood samples
      were colleted and the total DNA was extracted. The apoE genotypes were identified
      by multiplex amplification refractory mutation system (multi-AMRS), the apoCI
      promoter polymorphisms and AvaII polymorphisms of the apoCII and LDL-R gene were
      detected by using PCR-RFLP. Pairwise linkage disequilibrium coefficients (D, D')
      were estimated by the LINKAGE program. The interactions between genes with
      alcohol drinking and smoking were analyzed by using multivariate logistic
      regression models. RESULTS: The differences of systolic/diastolic blood pressure,
      total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C)
      concentrations, smoking and drinking were significant between subjects with CAD
      and controls. The frequencies of apoE gene epsilon 3/4 genotype (25.9%) and
      epsilon 4 (13.9%) in CAD were significantly higher than those in controls (12.5%
      and 6.9%, respectively, p < 0.05). A significant difference was also found for
      the apoCI locus, the frequencies of H2 allele were 20.5% in the CAD and 11.3% in
      the control. Linkage disequilibrium coefficient D' was 0.672 (p < 0.01) between
      apoE and apoCI genes. Significant differences for a deficit of epsilon 3-H1-T1
      and excess of epsilon 4-H2-T1 was found in CAD by estimation of the haplotype
      frequencies. After control for possible confounding factors, the multivariate
      logistic analysis showed that epsilon 4, H2 allele, smoking and drinking were
      risk factors of CAD. A significant interaction among epsilon 4, H2 and smoking
      was observed (OR 18.3, 95% CI: 2.35-150.81, p < 0.05), it was a multiplicative
      model. An additive model was shown among epsilon 4, H2 and drinking (OR12.7, 95%
      CI: 2.8-58.6, p < 0.05). CONCLUSION: The results suggested that both apoE and
      apoCI on chromosome 19 were the susceptibility locus for CAD, their linkage
      disequilibrium should be responsible for the development of CAD. Drinking and
      smoking enhance the genetic predisposition to CAD.

PMID- 16459142
TI  - Binational study of pediatric blood lead levels along the United States/Mexico
      border.
AB  - To evaluate lead exposure among children living in border communities, the states
      of Arizona and New Mexico in the United States (US), and the states of Sonora and
      Chihuahua in Mexico collaboratively requested that the Centers for Disease
      Control and Prevention (CDC) provide technical assistance to document pediatric
      blood lead levels (BLLs) in children living along this part of the US/Mexico
      border. Two studies were conducted to evaluate BLLs of children aged 1-6 years.
      In 1998, 1210 children were tested in the Arizona/Sonora study; in 1999, 874
      children were tested in New Mexico/Chihuahua. Overall geometric mean BLL was 32.5
      microg/l (95% Confidence Interval 31.5-33.5) with BLLs ranging from below limit
      of detection to 320.0 microg/l. Mean BLLs were higher among children living on
      the Mexican side of the border (43.2 microg/l) compared to those on the US side
      (22.3 microg/l). Mean BLLs ranged from 14.9 to 31.2 microg/l at the US sites and
      from 26.9 to 55.2 microg/l at the Mexican sites. This study used a convenience
      sample and cannot be considered representative of the general population.
      Nonetheless, the range of mean BLLs among the sites and especially the higher
      mean BLLs among children living in the border communities in Mexico suggests
      different exposures to lead and warrants further attention.

PMID- 16459143
TI  - Survey and significance of filamentous fungi from tap water.
AB  - Fungi in drinking water are involved in the production of tastes and odours in
      water. Health problems are possible, originating from mycotoxins, animal
      pathogens and allergies. This report concerns the surveillance of mesophilic
      fungi in tap water and assessment of their potential for causing problems. The
      methods for the determination of the filamentous fungi (ff) were filtering,
      swabbing and baiting. Tap water, half-strength corn meal, neopeptone-glucose rose
      Bengal aureomycin (NGRBA) and oomycete selective agars for the enumeration of
      colony forming units (cfu) were used. Samples were taken consecutively over 16
      months. Filtration and NGRBA gave the highest ff counts. A total of 340 taxa were
      isolated. There appeared to be a negative correlation between bacterial and yeast
      (b/y) and ff counts. Highest counts were found in winter months for ff and in the
      warmer months for b/y. Penicillium (40.6%) and Acremonium (38.8%) were the most
      frequently isolated ff. There was a difference in the pattern of isolation of the
      key taxa with season: penicillia predominated in early summer and Acremonium in
      winter. P. expansum was isolated in high numbers in May 2004. This species is
      associated with the production of the mycotoxin patulin and the odour secondary
      metabolite geosmin. P. brevicompactum was detected throughout the sampling period
      and is known to produce the immunosuppressive drug mycophenolic acid. Acremonium
      is associated with ocentol production which is responsible for bad tastes and
      flavours. The remaining taxa were Phialophora sp. (4.1%), Cladosporium sp.
      (3.5%), Rhizopus stolonifer (2.9%), Chaetomium sp. (0.6%), Alternaria sp. (0.3%),
      Aspergillus sp. (0.3%), mycelia sterilia (2.6%) and unidentified (6.2%). It is
      emphasised that few Aspergillus and no Fusarium strains were isolated. Rhizopus
      stolonifer was obtained. However, none of the fungi isolated at mesophilic
      temperature used could be described as being involved with pathogenicity per se.

PMID- 16459144
TI  - Comparison of different biological methods for the assessment of ecotoxicological
      risks.
AB  - To test the effects of heavy metals in river water, we compared the sensitivity
      of seven different biological test methods, using bacteria (Vibrio fischeri),
      human FL cells, protozoans (Paramecium spp.), nematodes (Rhabditis oxycerca),
      aquatic plants (Lemna minor), and fishes (Leuciscus idus melanotus). As test
      substance we used a representative mixture of 3.0 microg/l As, 2.5 microg/l Pb,
      0.8 microg/l Cd, 1.7 microg/l Cr, 3.9 microg/l Cu, 6.7 microg/l Ni, 0.4 microg/l
      Hg, and 23.0 microg/l Zn, imitating the detectable heavy metal contamination of
      the Odra estuary (NE Germany/NW Poland). This mixture was defined as normal
      concentration (NC). Most sensitive was the test with L. minor (exposure time 10
      d). The plants already showed phytotoxic effects at the heavy metal concentration
      found in the Odra estuary. Test systems with human cells, protozoans, and
      nematodes (exposure time 1-7 d) reacted at concentrations 85-100 times above the
      NC. Fish toxicity (exposure time 2 d) occurred from 130-fold concentration
      upwards. In contrast, the standard test carried out with luminescent bacteria
      (exposure time 30 min) was affected only at > 1000-fold concentrations. This test
      is therefore not suitable as an early warning system to detect ecological risks.
      Even the NC of heavy metals measured in the Odra estuary inhibits cells and the
      growth of aquatic plants. Of the single heavy metals tested, copper produced the
      strongest effects. Therefore, the reduction of heavy metal emissions, especially
      of copper-which can amplify the toxicity of other heavy metals-should be a task
      of highest priority.

PMID- 16459145
TI  - Reference values for metabolites of pyrethroid and organophosphorous insecticides
      in urine for human biomonitoring in environmental medicine.
AB  - Pesticides are widely used throughout the world in agriculture to protect crops,
      and in public health to control diseases transmitted by vectors or intermediate
      hosts. After the prohibition of organochlorines, such as DDT, today mainly
      pyrethroids and organophosphorous insecticides are used. With reliable and
      sensitive analytical methods for detecting metabolites of organophosphorous and
      pyrethroid insecticides in urinary specimens of the general population several
      studies have been published on internal exposure to these insecticides of the
      population in Germany. In total, data on levels of metabolites of
      organophosphorous acids in urine of about 1200 children and adults have been
      published, as well as data on levels of pyrethroid metabolites in urine of about
      2100 children and adults. In Germany, reference values for environmental
      pollutants related to the population are established continuously by the Human
      Biomonitoring Commission of the German Federal Environmental Agency, preferably
      based on data gained by representative studies. Reference values are defined as
      the 95th percentile, rounded off within the 95% confidence interval of the
      population studied. Since there is a need for reference values to characterise
      the population's exposure to organophosphates and pyrethroids, and since there
      are different studies available from Germany that agree quite well with data from
      other industrialised countries, the Commission has derived reference values from
      the available data, though none of the studies had fulfilled criteria on
      representativity. Reference values for metabolites of organophosphorous acids are
      as follows: DMP 135 microg/l, DMTP 160 microg/l and DEP 16 microg/l and for
      metabolites of pyrethroids: cis-Cl2CA 1 microg/l, trans-Cl2CA 2 microg/l and 3
      PBA 2 microg/l. As the volume-related concentrations of organophosphate and
      pyrethroid metabolites show no significant age-dependence, the reference values
      derived are not age-stratified. Though based merely on statistical and not on
      toxicological data, levels analysed above the reference levels, when reliably
      measured (verified several times), should prompt environmental health
      practitioners to search for sources, within the bounds of proportionality. In
      addition to accidental poisoning, possible sources include indoor contamination
      following improper pest control operations in homes as well as in pets and food
      products contaminated by these pesticides.

PMID- 16459146
TI  - The dichotomous role of IL-2: tolerance versus immunity.
AB  - Interleukin-2 (IL-2) is a well-known T-cell growth factor, which is traditionally
      implicated in the agonistic stimulation of immune responses. Recent work,
      however, has uncovered an unexpected function of this cytokine. In particular, IL
      2 appears crucial to maintaining peripheral tolerance by supporting the survival
      and function of CD25+ CD4+ regulatory T cells. A recent study examining the role
      of IL-2 in the peripheral generation of regulatory T cells from apparently naive
      T cells has gone some way to reconciling the seemingly opposing functions of this
      cytokine.

PMID- 16459148
TI  - The evolution of myiasis in humans and other animals in the Old and New Worlds
      (part I): phylogenetic analyses.
AB  - Myiasis, the infestation of live vertebrates with dipterous larvae, seems to take
      two distinct forms that, it has been suggested, evolved from two distinct
      phylogenetic roots: saprophagous and sanguinivorous. However, the convergent
      evolution of morphological and life-history traits seems to have had a major role
      in simplifying this overall assessment of the evolutionary routes by which
      myiasis arose. Moreover, this somewhat simplistic division is further complicated
      by the existence of both ectoparasitic and endoparasitic species of myiasis
      causing Diptera, the evolutionary affinities of which remain to be resolved. To
      understand how different forms of parasitism arose, the evolution of the various
      groups of myiasis-causing flies must be separated from the evolution of the
      myiasis habit per se. Until recently, evolutionary studies of myiasis-causing
      flies were little more than discussions of morphology-based taxonomy. Since the
      mid-1990s, however, several formal phylogenies - based on both morphological and,
      increasingly, molecular data - have been published, enabling reassessment of the
      hypotheses concerning myiasis evolution. In part I of this review, we focus on
      some recent landmark studies in this often-neglected branch of parasitology and
      draw together phylogenetic studies based on molecular and morphological data to
      provide a framework for the subsequent analysis of biochemical, immunological,
      behavioural, biogeographical and fossil evidence relating to the evolution of
      myiasis.

PMID- 16459150
TI  - Low-grade chronic metabolic acidosis is a contributory mechanism in the
      development of chronic epilepsy.
AB  - In most people with epilepsy, the condition is readily controlled, but 20-30%
      develop chronic epilepsy. An estimated 80,000 patients with epilepsy require
      ongoing specialist care in the United Kingdom. Nutrition may be a factor in the
      development of chronic epilepsy. Modern Western diets are thought to produce a
      low-grade chronic metabolic acidosis. The hydrogen ion, H+, is a potent modulator
      of NMDA-activated currents, and in cultured neurons, increased external [H+]
      strongly suppresses these currents. The effect of chronic metabolic acidosis in
      vivo has not been fully studied. It is possible that low-grade chronic metabolic
      acidosis chronically inhibits the NMDA-activated currents, and this may lead to
      upregulation of the NMDA receptor. This would result in a greater hyperexcitable
      state and may contribute to the development of chronic epilepsy.

PMID- 16459151
TI  - Electroacupuncture-induced pressor and chronotropic effects in anesthetized rats.
AB  - The effects of electroacupuncture (Ea) on circulatory dynamics were investigated
      in anesthetized rats. The arterial blood pressure (BP) and the heart rate (HR) in
      response to Ea stimulations at the Tsusanli point (St-36) and the Hoku point (Li
      4) were tested by a low frequency Ea (2 Hz; LFEa) and a high frequency Ea (20 Hz;
      HFEa) with stimulation intensities 20 times the motor threshold. Neither the HR
      nor the BP was affected when the Tsusanli point was stimulated. Whereas, Ea
      stimulations at the Hoku point elicit chronotropic and pressor effects. The
      patterns of pressor responses caused by the LFEa were different from that of an
      HFEa, i.e., the LFEa elicited a tonic effect, while an HFEa had a phasic one. The
      HFEa-induced pressor and chronotropic effects were attenuated, while the LFEa
      induced effects were completely blocked by an intravenous infusion of an alpha
      adrenergic blocker (moxisylyte 0.2 mg/min/kg, i.v., for 20 min). A co-infusion
      with alpha-and beta-adrenergic blockers (propanolol 0.2 mg/min/kg, i.v., for 20
      min) completely blocked the HFEa-induced pressor and chronotropic effects. We
      concluded that Ea stimulations, at the Hoku acupoint, with appropriate
      stimulation parameters can increase and maintain BP. Furthermore, the LFEa
      stimulation activates sympathetic vasomotor tone, whereas the HFEa stimulation
      causes an additional potentiation on the sympathetic drive to the heart.

PMID- 16459149
TI  - Selective targeting of checkpoint kinase 1 in tumor cells with a novel potent
      oncolytic adenovirus.
AB  - DNA-damage checkpoints are activated to arrest cells and promote survival upon
      genotoxic challenge. Efforts have been taken to target checkpoint kinase 1 (chk1;
      approved gene symbol CHEK1), a crucial checkpoint modulator, for therapeutic
      intervention. However, improvement of the potency and specificity of such
      therapeutics remains a major challenge. This prompted us to develop a novel chk1
      targeting strategy by constructing a potent oncolytic adenovirus (M2). M2 was
      generated by combining two artificial features into a wild-type adenovirus type 5
      genome. First, M2 was engineered with a 27-bp deletion in the E1A region to
      confer tumor-selective replication. Second, an antisense chk1 cDNA was
      substituted for viral E3 6.7K and gp19K genes. In this design, M2 exploited the
      adenovirus E3 promoters to express antisense chk1 cDNA in a viral replication
      dependent fashion and preferentially silenced the chk1 gene in tumor cells. By
      virtue of combining oncolysis with chk1 targeting, M2 exhibited potent
      antitumoral efficacy in vitro and in vivo. Systemic administration of M2, plus a
      low dose of cisplatin, cured 80% of orthotopic hepatic carcinoma mouse models
      that were otherwise resistant to cisplatin. These findings have directed us
      toward the development of novel oncolytic adenoviruses that will be potentially
      applicable to a wide range of molecular-based therapeutics.

PMID- 16459152
TI  - Differential gene expression in the developing mouse ureter.
AB  - In many instances, kidney dysgenesis results as a secondary consequence to
      defects in the development of the ureter. Through the use of mouse genetics a
      number of genes associated with such malformations have been identified, however,
      the cause of many other abnormalities remain unknown. In order to identify novel
      genes involved in ureter development we compared gene expression in embryonic day
      (E) 12.5, E15.5 and postnatal day (P) 75 ureters using the Compugen mouse long
      oligo microarrays. A total of 248 genes were dynamically upregulated and 208
      downregulated between E12.5 and P75. At E12.5, when the mouse ureter is comprised
      of a simple cuboidal epithelium surrounded by ureteric mesenchyme, genes
      previously reported to be expressed in the ureteric mesenchyme, foxC1 and foxC2
      were upregulated. By E15.5 the epithelial layer develops into urothelium,
      impermeable to urine, and smooth muscle develops for the peristaltic movement of
      urine towards the bladder. The development of these two cell types coincided with
      the upregulation of UPIIIa, RAB27b and PPARgamma reported to be expressed in the
      urothelium, and several muscle genes, Acta1, Tnnt2, Myocd, and Tpm2. In situ
      hybridization identified several novel genes with spatial expression within the
      smooth muscle, Acta1; ureteric mesenchyme and smooth muscle, Thbs2 and Col5a2;
      and urothelium, Kcnj8 and Adh1. This study marks the first known report defining
      global gene expression of the developing mouse ureter and will provide insight
      into the molecular mechanisms underlying kidney and lower urinary tract
      malformations.

PMID- 16459153
TI  - Involvement of hepatocyte growth factor in the development of bone metastasis of
      a mouse mammary cancer cell line, BALB/c-MC.
AB  - Some cancers frequently affect the skeleton, and the bone microenvironment
      supports growth of certain cancer cells. After tumors metastasize to bone, they
      stimulate osteoclastogenesis and expand in the bone tissue. Hepatocyte growth
      factor (HGF), which was originally identified as a potent mitogen for
      hepatocytes, promotes tumor growth, invasion and metastasis. HGF is mainly
      produced by cells of mesenchymal origin, and osteoblasts/osteocytes and bone
      marrow stromal cells originate from mesenchymal cells. However, it is not clear
      what effect HGF has on tumor progression in bone metastasis. In the present
      study, we investigated the roles of HGF in bone metastasis using the mouse
      mammary cancer cell line BALB/c-MC. Cancer cells injected into hearts of mice
      metastasized to bone in their hind limbs. HGF immunoreactivity was detected in
      the stroma surrounding the tumor nests, and blood vessels expressing CD31 (a
      marker of endothelial cells) were observed in the HGF-positive area. To identify
      the cells producing HGF, we measured concentration of HGF in culture media. HGF
      concentration was elevated in osteoblast cultures (3.13+/-0.25 ng/ml), whereas
      HGF was undetectable (<0.4 ng/ml) in BALB/c-MC and bone marrow cell cultures. HGF
      concentration in osteoblast cultures increased 2.5-fold in response to 10(-6) M
      PGE(2). Addition of HGF to BALB/c-MC cultures caused doubling of the cell number.
      Moreover, Western blot analysis revealed expression of c-Met/HGF receptor by
      BALB/c-MC. In the Matrigel invasion chamber assay, addition of HGF to the bottom
      well increased the rate at which BALB/c-MC invaded the bottom well through the
      membrane. Furthermore, when osteoblasts were cultured in the bottom well, the
      number of BALB/c-MC cells that invaded the bottom well through the membrane
      increased 3.7-fold, compared to assays without osteoblasts. Addition of NK4, an
      inhibitor of HGF, completely abolished the enhancement of the invasive potential
      of the BALB/c-MC cells in the presence of osteoblasts. These findings suggest
      that HGF produced by osteoblasts induces migration of cancer cells from
      sinusoidal capillaries to bone marrow space and stimulates growth of cancer cells
      in the bone microenvironment. Thus, osteoblasts appear to promote bone metastasis
      of some cancers via HGF-c-Met signaling.

PMID- 16459154
TI  - Wnt signaling activation during bone regeneration and the role of Dishevelled in
      chondrocyte proliferation and differentiation.
AB  - Wnt signaling is intrinsically involved in diverse cellular activities during
      cell differentiation, early embryonic development and organogenesis. Although
      much is known regarding the effects of Wnt signaling in the developing skeletal
      system, its role during regeneration remains unclear. Herein, we show
      transcriptional activation of specific members and target genes of the Wnt
      signaling pathway. Specifically, all of the Wnt signaling members and target
      genes analyzed were found to be upregulated during the early stages of fracture
      repair, with the exception of LEF1 whose expression was downregulated. In
      addition, spatial expression analysis of Dishevelled (Dvl) and beta-catenin in
      the fracture callus revealed an identical pattern of expression with both
      proteins localizing in osteoprogenitor cells of the periosteum, osteoblasts and
      proliferating/pre-hypertrophic chondrocytes. Further, in vitro knockdown of all
      three Dvl isoforms in chondrocytes using small interfering RNAs (siRNA) leads to
      partial inhibition of cell proliferation and differentiation, decreased
      expression of chondrogenic markers (ColII, ColX, Sox9) and suppressed nuclear
      accumulation of unphosphorylated beta-catenin. Taken together, these data verify
      our previous finding that the Wnt signaling pathway is activated during bone
      regeneration, by characterizing the temporal and spatial expression of a broad
      spectrum of Wnt-signaling molecules. Our data also suggest that all three Dvl
      isoforms, acting through the Wnt canonical pathway, are critical regulatory
      molecules for chondrocyte proliferation and differentiation.

PMID- 16459155
TI  - Dissociation of mineral and collagen orientations may differentially adapt
      compact bone for regional loading environments: results from acoustic velocity
      measurements in deer calcanei.
AB  - In limb bone diaphyses, it is hypothesized that collagen and extra-fibrillar
      mineral are aligned differently in relatively simple loading conditions (e.g.,
      habitual longitudinal compression) when compared to complex or potentially
      deleterious strain environments (e.g., habitual shear or tension). These putative
      differences in collagen/mineral organization might be adaptations that enhance
      toughness and fatigue resistance by controlling the direction of microdamage
      propagation. This study examined relationships between the non-uniform strain
      distribution of wild deer calcanei and elastic anisotropy of cortical bone
      specimens in three preparations: (1) demineralized (collagen only), (2)
      deproteinized (mineral only), and (3) untreated. Using simulated functional
      loading, the following strain data were obtained from the dorsal "compression",
      plantar "tension", and medial and lateral ("neutral axis") cortices of one
      calcaneus of each of seven pairs: (1) peak strain magnitude, (2)
      prevalent/predominant strain mode (compression, tension, shear), and (3)
      principal strain orientation with respect to the bone's long axis. In the
      contralateral calcanei, elastic anisotropy ratios (ARs) were calculated using
      acoustic velocity (longitudinal and transverse) measurements from a pair of
      orthogonally sliced specimens (representing each of three preparation types) from
      each cortex. In a separate set of seven adult calcanei, predominant collagen
      fiber orientation (CFO) was measured using circularly polarized light (CPL) in
      the four cortical locations. Results showed that, in general, elastic anisotropy
      was significant in each region, with ARs being significantly different from
      isotropy (where AR=1.0). Compared to CFO, mineral orientation more strongly
      influenced this anisotropy, which was most notable in the plantar "tension"
      cortex. High correlations (r values from -0.675 to -0.734, P<0.05) were found
      between collagen anisotropy obtained from acoustic data when compared to the CPL
      data. Significant correlations of mineral and collagen anisotropy were also found
      between strain mode, magnitude, and orientation (all r values approximately 
      0.750). The habitual compression, tension, and shear (neutral axis) regions also
      had different collagen/mineral organizations, which may be important in
      accommodating the well-known disparity in the mechanical properties of bone in
      these loading modes.

PMID- 16459156
TI  - Young-elderly differences in bone density, geometry and strength indices depend
      on proximal femur sub-region: a cross sectional study in Caucasian-American
      women.
AB  - Fragility fractures at the trochanter (TR) and the femoral neck (FN) have
      distinct etiologies, but the underlying age-related structural changes at these
      proximal femoral sub-regions are poorly understood. 28 young (41+/-3 years) and
      124 elderly (74+/-3 years) healthy Caucasian women underwent volumetric
      quantitative computed tomography at the hip. Integral (i), cortical (c) and
      trabecular (t) bone mineral density and content (BMD, BMC) were measured.
      Geometric parameters included cross sectional area (CSA), and volumes of the
      integral, cortical and trabecular regions (VOL). Structural measures included
      indices of compressive (Compstr) and bending (BSI) strength. After adjusting for
      height and weight, an F-test was used to compare the TR and the FN mean values
      between young and elderly and to test for interaction to compare logarithmic
      difference of young and elderly (log(Young)-log(Elderly), Y/Ed) between the FN
      and the TR in an ANOCOVA model. All BMC, iBMD and tBMD values were significantly
      lower in elderly than in young women, with the largest Y/Ed in the FN tBMC and
      tBMD (P<0.0011 and P<0.0001). cBMD in young and elderly groups was not
      significantly different at the TR while at the FN it was greater (P=0.0075) in
      elderly than young women, showing significant Y/Ed (P=0.0003) dependence on
      skeletal site. Elderly women had significantly larger iVOL and CSA values
      (0.0001<P<0.0051), except for the FN iVOL. cVOL values were smaller in elderly
      than young women (P<0.0001). Y/Ed in bone geometry differed by sub-region only
      for cVOL measures (P=0.0267). Despite larger CSA and iVOL measures in elderly,
      the younger women had greater Compstr (P<0.0001) and BSI (P=0.0051). Thus,
      although both the TR and the FN appear to increase in size with age, this
      enlargement is insufficient to protect against loss of bone strength.

PMID- 16459157
TI  - Cloning and structural characterization of the 6-phosphogluconate dehydrogenase
      locus of the medfly Ceratitis capitata and the olive fruit fly Bactrocera oleae.
AB  - The pentose phosphate cycle is considered as a major source of NADPH and pentose
      needed for nucleic acid biosynthesis. 6-Phosphogluconate dehydrogenase (6PGD), an
      enzyme participating in this cycle, catalyzes the oxidative decarboxylation of
      6PGD to ribulose 5-phosphate with the subsequent release of CO(2) and the
      reduction of NADP. We have determined the genomic sequences of 6PGD of two
      species of Tephritidae, the medfly Ceratitis capitata and olive fruit fly
      Bactrocera oleae, and constructed a three-dimensional model of 6PGD of C.
      capitata based on the homologous known sheep structure. In a comparative study of
      6PGD sequences from seven species, all the conserved and variable sites of the
      enzyme were analyzed and the regions of functional importance were localized, an
      attempt promoted also by the direct involvement of the enzyme in various human
      diseases. The enzymes between the two species of Tephritidae have a very high
      homology and further examination of the variable positions with respect to the
      highly conserved binding site residues enabled their grouping in three distinct
      categories, with possible association to dimer formation, functional specificity,
      and antigenicity. Moreover, placement of sequence differences on the 3-D model
      suggests probable sites accommodating variations appearing at the allozymic
      variants of both species.

PMID- 16459160
TI  - Unexpected gastrointestinal tract conditions.

PMID- 16459162
TI  - Restless legs syndrome: the CNS/iron connection.

PMID- 16459163
TI  - Effects of hepatitis B virus X protein on the development of liver cancer.
AB  - Hepatitis B virus (HBV) infections play an important role in the development of
      cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of HBV-related
      HCC, however, has not been fully described. Evidence suggests that the HBV X
      protein (HBx) plays a crucial role in the pathogenesis of HCC. The high
      occurrence of anti-HBx antibody in the serum of HCC patients indicates that it
      could be a prognostic marker of HBV infection and HCC. HBx stimulates and
      influences signal transduction pathways within cells. HBx also binds to such
      protein targets as p53, proteasome subunits, and UV-damaged DNA binding proteins.
      It also interacts with the cyclic AMP-responsive element binding protein, ATF-2,
      NFkappaB, and basal transcription factors. HBx is primarily localized to the
      cytoplasm, where it interacts with and stimulates protein kinases, including
      protein kinase C, Janus kinase/STAT, IKK, PI-3-K, stress-activated protein
      kinase/Jun N-terminal kinase, and protein kinase B/Akt. It is also found in the
      mitochondrion, where it influences the Bcl-2 family. This review examines the
      role of HBx in the life cycle of HBV as well as the various signal transduction
      pathways involved in the pathogenesis of HBV-induced hepatocarcinogenesis.

PMID- 16459164
TI  - Ferritin subunits in CSF are decreased in restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a neurological disorder that may be related to
      iron misregulation at the level of the central nervous system. Evidence that iron
      is involved in RLS comes from magnetic resonance imaging data, autopsy studies,
      analyses of cerebrospinal fluid (CSF), and correlations of symptoms with serum
      ferritin. To further examine the possibility that brain iron status is
      insufficient in RLS, we determined ferritin levels in the CSF. Specifically, we
      differentiated between the H- and L-subunits of ferritin, because these peptides
      are expressed from different chromosomes and have different functions. We
      measured H- and L-ferritin subunit levels in control and RLS human CSF using
      immunoblot analysis and found that both H- and L-ferritin are significantly
      decreased in early but not late-onset RLS. Additionally, we quantified total
      protein in each CSF sample to establish that the decrease in ferritin subunits in
      RLS did not reflect a decrease in total protein in CSF. Furthermore, we used
      equal amounts of total CSF protein in the immunoblot analyses, in contrast to
      previously published studies that provided only volumetric data, to determine
      which approach was more accurate for quantifying the amount of ferritin relative
      to other proteins in CSF. Our results establish a protein standard in RLS,
      provide a comparative analysis of protein-controlled versus volumetric immunoblot
      techniques, and argue for a profound loss of iron storage capacity in the brain
      in RLS, specifically in the early onset RLS phenotype. These data suggest that
      CSF ferritin levels may provide a biomarker for assisting in the diagnosis of
      RLS.

PMID- 16459165
TI  - Reduced podocyte expression of alpha3beta1 integrins and podocyte depletion in
      patients with primary focal segmental glomerulosclerosis and chronic PAN-treated
      rats.
AB  - Integrins attach cells to extracellular matrix (ECM) and mediate signals from ECM
      to cells or from cells to ECM. They regulate cell functions, including adhesion,
      migration, cell cycle regulation, and differentiation. Podocytes may detach from
      the glomerular basement membrane (GBM) and be excreted in the urine, and
      proteinuria is found in patients with primary focal segmental glomerulosclerosis
      (FSGS); both may be associated with loss of alpha3beta1integrins. In this study,
      we have examined the podocyte number in patients with primary FSGS and normal
      controls, and the alpha3- and beta1-integrin subunits expression of podocytes in
      patients with primary FSGS and chronic puromycin aminonucleoside (PAN)-treated
      rats by the morphometric, immunoperoxidase histochemical, and immunoelectron
      microscopic examination. We also measured their expression serially in rats that
      received repeated PAN injection. The results showed that the podocyte number was
      significantly decreased in patients with primary FSGS than in normal control (P <
      0.05). The immunostaining score showed that both alpha3- and beta1-integrin
      subunits on podocytes in patients with primary FSGS were significantly lower than
      in normal controls (both P < 0.01). The number of immuno-gold particles of alpha3
      and beta1-integrins at the effaced foot process area of patients with primary
      FSGS were also significantly decreased than that of normal controls (both P <
      0.05). The immunostaining score of both alpha3- and beta1-integrin subunits was
      negatively correlated with the degree of glomerular sclerosing score and the
      amount of daily protein loss, and they were positively correlated with the number
      of podocytes. Chronic 12-week PAN-treated rats showed similar findings with
      decreased immunostaining expression and immuno-gold particles of alpha3-integrin
      on podocytes than in normal control (both P < 0.05). The chronic PAN-treated rats
      also showed a trend toward gradually decreased immunostaining expression of
      alpha3-integrin subunit on podocyte during the progress from normal to FSGS
      state. These studies indicate that podocyte expression of alpha3- and beta1
      integrin subunits is significantly reduced in humans with primary FSGS and
      chronic PAN-treated rats, before the morphological changes of FSGS are observed.
      The decreased podocyte expression of alpha3beta1 integrins is closely related
      with podocyte depletion, glomerular sclerosis, and daily protein loss in patients
      with primary FSGS.

PMID- 16459167
TI  - Association of angiotensin-converting enzyme 2 gene A/G polymorphism and elevated
      blood pressure in Chinese patients with metabolic syndrome.
AB  - To establish whether angiotensin-converting enzyme 2 (ACE2) gene A/G single
      nucleotide polymorphism is associated with hypertension in Chinese patients with
      metabolic syndrome. The study was conducted in 353 patients with metabolic
      syndrome. The alleles of the ACE2 A/G polymorphism, which is located on the X
      chromosome, were detected using polymerase chain reaction and subsequent cleavage
      by Alu I restriction endonuclease. G allele frequencies in patients with
      metabolic syndrome were 36.6% in female subjects and 43.4% in male subjects,
      respectively. Female patients with metabolic syndrome who carry the GG genotype
      had a significantly higher diastolic blood pressure compared with other
      genotypes. Multivariate logistic regression showed that female gender (P = 0.019)
      and carrying only the G allele (odds ratio 2.83 [95% CI 1.36 to 5.91]; P = 0.005)
      were significantly associated with increased diastolic blood pressure. It is
      concluded that the ACE2 A/G polymorphism is associated with hypertension in
      patients with metabolic syndrome.

PMID- 16459166
TI  - The antitumor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl
      disulfide) decreases thioredoxin-1 and VEGF levels in cancer patient plasma.
AB  - Thioredoxin-1 (Trx-1) is a small redox protein that is overexpressed in many
      human tumors, where it is associated with aggressive tumor growth and decreased
      patient survival. Trx-1 is secreted by tumor cells and is present at increased
      levels in the plasma of cancer patients. PX-12 is an irreversible inhibitor of
      Trx-1 currently in clinical development as an antitumor agent. We have used SELDI
      TOF mass spectroscopy to measure plasma Trx-1 from patients treated with PX-12
      during a phase I study. Mean plasma Trx-1 levels at pretreatment were
      significantly elevated in the cancer patients at 182.0 ng/mL compared with 27.1
      ng/mL in plasma from healthy volunteers. PX-12 treatment significantly lowered
      plasma Trx-1 in cancer patients having the highest plasma Trx-1 pretreatment
      levels. High-plasma vascular endothelial growth factor (VEGF) levels have been
      correlated to decreased patient survival. PX-12 treatment also significantly
      lowered plasma VEGF levels in cancer patients with high pretreatment VEGF levels.
      SELDI-TOF mass spectrometry identified seven additional plasma proteins whose
      levels decreased after PX-12 administration, one of which was identified as a
      truncated form of transthyretin. The results of this study suggest that the
      lowering of elevated levels of plasma Trx-1 in cancer patients may provide a
      surrogate for the inhibition of tumor Trx-1 by PX-12. Furthermore, PX-12
      decreases plasma VEGF levels that may contribute to the antitumor activity of PX
      12.

PMID- 16459168
TI  - Identifying type Vicenza von Willebrand disease.
AB  - Increased clearance of von Willebrand factor (VWF) is one of the main features of
      type Vicenza von Willebrand disease (VWD), a variant with plasma and platelet VWF
      level discrepancies and unusually large VWF multimers. Diagnosing type Vicenza
      VWD may not be easy, due to its heterogeneous phenotype. Here we describe the
      criteria we adopted to identify type Vicenza in a large group of VWD patients.
      Emphasizing the contribution of platelet VWF by comparison with plasma values, a
      first step involved selecting the candidate Vicenza patients on the basis of low
      or very low plasma VWF and a normal platelet VWF content. After excluding type 2A
      and 2B VWD patients, who may have normal platelet VWF, 18 candidates were found
      to meet our selection criteria. Genetic analysis revealed that 15 patients (from
      5 unrelated families) were type Vicenza VWD and that all carried both G2220A and
      G3614A type Vicenza mutations barring one, who only had the G3614A mutation. All
      patients had a reduced VWF survival, and all but the patient with the G3614A
      mutation alone had ultralarge VWF multimers. Thus, low-plasma VWF associated with
      a normal platelet VWF content may be a first useful indicator for identifying
      type Vicenza VWD patients.

PMID- 16459169
TI  - A restless investigator.

PMID- 16459170
TI  - Antisaccade performance of schizophrenia patients: evidence of reduced task-set
      activation and impaired error detection.
AB  - The antisaccade task is well suited to study the interplay between environmental
      stimuli and action goals in controlling behavior. It requires subjects to look to
      the mirror position of visual stimuli. Schizophrenia patients usually show
      enhanced rates of erroneous saccades toward the stimulus. The present study was
      designed to investigate the role of task set activation and error detection for
      this impairment. Fifteen patients with a diagnosis of schizophrenia and 15
      control subjects made antisaccades under standard conditions and under precue
      conditions. In the precue conditions the imperative visual stimulus was
      immediately preceded by short precues on either the same or the opposite side.
      Subjects had to evaluate their performance on each trial. Schizophrenia patients
      showed enhanced error rates on the standard condition and after same side precues
      but not after opposite side precues. Opposite side precues entailed increased
      errors in both groups, but the increase was weaker in schizophrenia patients.
      This lower precue effect in schizophrenia is proposed to reflect reduced
      activation of the task set for antisaccades in schizophrenia. The study also
      revealed strongly impaired error detection in schizophrenia. The relative roles
      of task-set activation and error detection for poor antisaccade performance in
      schizophrenia are discussed.

PMID- 16459171
TI  - Accumulated increase in neuropeptide Y and somatostatin gene expression of the
      rat in response to repeated electroconvulsive stimulation.
AB  - The mechanisms by which electroconvulsive therapy (ECT) causes its antidepressive
      effect are unknown. Because ECT requires repeated induction of electroconvulsive
      seizures, adaptive changes in the brain and regulation of gene expression, are
      likely to be the fundamental basis on which ECT acts. Neuropeptide Y (NPY) gene
      expression is increased after multiple electroconvulsive stimulations (ECS) and
      since it also has anticonvulsant and antidepressant properties, it has led to the
      hypothesis that the beneficial effect of ECT is mediated via its activation of
      NPY-dependent neurotransmission. We have therefore examined in detail the
      temporal profile of NPY gene expression, using in situ hybridisation
      histochemistry in the rat dentate gyrus and piriform cortex - two brain areas
      centrally involved in seizure regulation. NPY mRNA in both regions was found to
      increase gradually with the number of ECS, reaching a maximum (550-700%) after
      approximately 14 ECS where no further increase was achieved by additional ECS. A
      number of 14 ECS was also shown to exert anticonvulsant activity against kainic
      acid seizures. In the dentate gyrus, repeated ECS also caused a gradual, but
      smaller, increase in the expression of somatostatin (SS) - a neuropeptide that is
      co-localised with NPY and also has anticonvulsant effects. These results shows
      that NPYergic and, to a lesser extent, SSergic neurotransmission is activated by
      ECS and support the hypothesis that these neuropeptides could play a central role
      in the anticonvulsant and antidepressant effect of ECT.

PMID- 16459173
TI  - An update on the role of epidermal growth factor receptor inhibitors in non-small
      cell lung cancer.
AB  - Within the past 2 years, epidermal growth factor receptor (EGFR) inhibitors have
      moved from experimental agents to approved drugs for the management of advanced
      non-small cell lung cancer (NSCLC). This evolution has been accompanied by
      dramatic improvements in the understanding of how these drugs work and the
      clinical populations that may benefit. The identification of mutations in the ATP
      binding domain of the EGFR that predict for dramatic responses introduces the
      possibility of truly individualized therapy in a subset of advanced NSCLC
      patients. The fact that these mutations may be more prevalent in certain patient
      populations, including patients of Asian ethnicity, female gender, and never
      smoker status, raises intriguing questions regarding the pathogenesis of lung
      cancer. Another emerging area in the understanding of these agents revolves
      around the clinical observation that acneform rash may predict for superior
      outcome and the question of how this rash may relate to polymorphisms in the EGFR
      gene. EGFR polymorphisms, both germline and somatic, may be a relevant factor in
      unraveling the mechanism of the benefit of erlotinib in patients who do not
      harbor an EGFR ATP-binding site mutation. Numerous questions have arisen
      regarding how to best incorporate EGFR-targeted agents into patient management,
      as well as the role of the clinical laboratory in these decisions and the design
      of future trials.

PMID- 16459174
TI  - Ongoing first-line studies of epidermal growth factor receptor tyrosine kinase
      inhibitors in select patient populations.
AB  - The epidermal growth factor receptor (EGFR) has emerged as an attractive
      therapeutic target for patients with non-small cell lung cancer (NSCLC). However,
      despite its almost universal presence in NSCLC tumors, therapeutic inhibition of
      EGFR has resulted in significant tumor regressions in only 10% to 20% of
      patients. Several investigations over the last 12 months have uncovered somatic
      mutations in EGFR that underlie the sensitivity to EGFR inhibitors. Somatic
      mutations in EGFR are found more frequently in patients with adenocarcinomas,
      nonsmokers, patients of Asian ethnicity, and in females. These same subgroups of
      patients have previously been identified as those most likely to respond to EGFR
      tyrosine kinase inhibitors (TKIs). Information to date suggests that patients
      with EGFR mutations will derive the greatest benefit as measured by response
      rate, time to progression, and survival from EGFR inhibitors. In addition, data
      on EGFR amplification as a predictor of outcome with EGFR TKI therapy is also
      emerging. These therapeutic approaches are now being introduced as initial
      therapy for specific subgroups of patients defined by either clinical or
      molecular characteristics that predict for response to EGFR TKIs. The rationale
      and design of these trials will be reviewed.

PMID- 16459175
TI  - Targeting angiogenesis in lung cancer.
AB  - The prognosis for the majority of patients with lung cancer remains poor, and
      treatment strategies including newer generation chemotherapeutics have not
      improved survival. New approaches are required to further improve patient outcome
      and survival. Recently, key molecules involved in signal transduction pathways
      that contribute to tumor growth have been identified as therapeutic targets,
      particularly molecules involved in cellular proliferation and angiogenesis. Novel
      therapeutics that specifically target angiogenesis have shown promise as single
      agents and in combination with standard chemotherapy. The results of recent
      studies validate the use of this class of targeted therapeutics as an important
      new treatment modality in cancer therapy. This review will focus on a discussion
      of antiangiogenic therapeutic monoclonal antibodies in development for the
      treatment of non-small cell lung cancer.

PMID- 16459176
TI  - The emerging role of vascular endothelial growth factor receptor tyrosine kinase
      inhibitors.
AB  - In the United States, non-small cell lung cancer (NSCLC) constitutes 85% of all
      newly diagnosed lung cancers. Over the past 40 years, the 5-year survival rates
      in NSCLC have improved from 6% to 15%, with surgery remaining the most curative
      approach. However, resection is feasible in less than 35% of patients at
      diagnosis, and 40% to 50% of newly diagnosed patients present with metastatic
      disease. Platinum-based combination chemotherapy is standard treatment for these
      patients, but improvement beyond platinum doublets has not been achieved.
      Therefore, a clear-cut need exists for new treatment approaches for NSCLC.
      Targeted therapies, particularly angiogenesis inhibitors, are hoped to facilitate
      therapeutic progress. Neovascularization not only allows for the continued growth
      of the primary tumor, but also provides migrating tumor cells access to the
      systemic circulation, facilitating metastasis. A number of studies have shown a
      clear correlation between vascular endothelial growth factor (VEGF) expression,
      microvessel density, and impaired prognosis. Monoclonal antibodies directed
      against the VEGF and VEGF receptor have been studied in depth in advanced NSCLC.
      A randomized phase III trial evaluated the role of the anti-VEGF-A antibody
      bevacizumab in combination with paclitaxel and carboplatin versus chemotherapy
      alone in NSCLC. Based on toxicity observations from a phase II study, this trial
      excluded patients with squamous histology, brain metastases, or an ongoing need
      for therapeutic anti-coagulation or non-steroidal anti-inflammatory agents.
      Preliminary data confirmed a survival advantage of 12.5 months for patients in
      the bevacizumab arm compared with 10.2 months in the control arm (P = .0075),
      which showed that antiangiogenic therapies can be effective in NSCLC.
      Antiangiogenic therapies, including antibodies against VEGF, and, in particular,
      new small-molecule inhibitors of the VEGF receptor, are reviewed and discussed in
      detail.

PMID- 16459178
TI  - Applying DOE's Graded Approach for assessing radiation impacts to non-human biota
      at the INL.
AB  - In July 2002, The US Department of Energy (DOE) released a new technical standard
      entitled A Graded Approach for Evaluating Radiation Doses to Aquatic and
      Terrestrial Biota. DOE facilities are annually required to demonstrate that
      routine radioactive releases from their sites are protective of non-human
      receptors and sites are encouraged to use the Graded Approach for this purpose.
      Use of the Graded Approach requires completion of several preliminary steps, to
      evaluate the degree to which the site environmental monitoring program is
      appropriate for evaluating impacts to non-human biota. We completed these
      necessary activities at the Idaho National Laboratory (INL) using the following
      four tasks: (1) develop conceptual models and evaluate exposure pathways; (2)
      define INL evaluation areas; (3) evaluate sampling locations and media; (4)
      evaluate data gaps. All of the information developed in the four steps was
      incorporated, data sources were identified, departures from the Graded Approach
      were justified, and a step-by-step procedure for biota dose assessment at the INL
      was specified. Finally, we completed a site-wide biota dose assessment using the
      2002 environmental surveillance data and an offsite assessment using soil and
      surface water data collected since 1996. These assessments demonstrated the
      environmental concentrations of radionuclides measured on and near the INL do not
      present significant risks to populations of non-human biota.

PMID- 16459177
TI  - Other compounds and targets in non-small cell lung cancer.
AB  - It has become increasingly apparent in recent years that a therapeutic plateau
      has been reached for patients with advanced stage non-small cell lung cancer
      (NSCLC) treated with conventional cytotoxic agents. As a result, investigators
      have directed their efforts toward the development of treatments encompassing
      novel targeted agents. Apoptosis is one of many cellular pathways currently under
      investigation as a therapeutic target for the treatment of NSCLC. Anti
      inflammatory agents, including cyclooxygenase inhibitors, have been shown to
      inhibit apoptosis and appear promising based on preclinical studies. However,
      several phase II studies indicate that this therapeutic strategy is unlikely to
      be successful. In contrast, the proteosome inhibitor bortezomib has shown promise
      in preliminary studies, and further efforts to elucidate the role this agent may
      play in the treatment of NSCLC are ongoing. Agonists of the tumor necrosis factor
      related, apoptosis-inducing ligand have also entered into early clinical studies
      in patients with NSCLC. Further studies will be needed to fully clarify how
      agents targeting the apoptotic pathway can be used in the treatment of NSCLC, but
      the results of current clinical trials suggest that certain agents may be active.

PMID- 16459179
TI  - Hemopoietic stem cell engraftment.

PMID- 16459180
TI  - Delivery of autologous bone marrow precursor cells into the spinal cord via
      lumbar puncture technique in patients with spinal cord injury: a preliminary
      safety study.

PMID- 16459182
TI  - Expansion of human umbilical cord blood SCID-repopulating cells using chromatin
      modifying agents.
AB  - OBJECTIVE: We investigated whether the addition of two chromatin-modifying
      agents, 5-aza-2'-deoxycytidine (5azaD) and trichostatin A (TSA), to cord blood
      (CB) CD34(+) cells in culture results in expansion of the numbers of severe
      combined immunodeficient (SCID) repopulating cells (SRC). MATERIALS AND METHODS:
      Human CB CD34(+) cells were cultured with cytokines in the presence or absence of
      5azaD/TSA. After 9 days of culture, the fold expansion of CD34(+) and
      CD34(+)CD90(+) cell numbers, colony-forming unit (CFU)-mix, cobblestone area
      forming cell (CAFC), and SRC numbers were determined. RESULTS: A 12.5-fold
      expansion of CD34(+)CD90(+) cells was observed in the 5azaD/TSA-treated cultures
      in comparison to the input cell numbers. Expansion of CD34(+)CD90(+) cells was
      associated with a 9.8-fold increase in the numbers of CFU-mix and 11.5-fold
      increase in CAFC. 5azaD/TSA treatment of the CB CD34(+) cells resulted in a 9.6
      fold expansion of the absolute number of SRC following 9 days of culture as
      determined by limiting dilution analysis. Expansion of cells maintaining
      CD34(+)CD90(+) phenotype was not due to the retention of a quiescent population
      of cells because all of the CD34(+)CD90(+) cells in the culture had undergone
      cellular division. 5azaD/TSA-treated CD34(+)CD90(+) cells, but not CD34(+)CD90(-)
      cells were responsible for in vivo hematopoietic repopulation potential of
      nonobese diabetic/SCID mice. CONCLUSION: Ex vivo expansion strategy using
      chromatin-modifying agents provides a potential avenue by which to expand the
      number of hematopoietic stem cells (HSC) with a single CB unit for use as an
      alternative source of HSC grafts for adult recipients.

PMID- 16459181
TI  - Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous
      transplantation of genetically modified hematopoietic stem cells in the rhesus
      macaque model.
AB  - OBJECTIVE: Gene transfer to hematopoietic stem cells has recently been
      demonstrated to benefit a small number of patients in whom a selective advantage
      is conferred upon genetically modified cells; however, in disorders where no such
      selective advantage is conferred, conditioning appears necessary to allow
      adequate engraftment. To decrease the toxicity profile, we sought to develop
      nonmyeloablative conditioning regimens and in this work, explored the use of
      intravenous busulfan in a large animal model. METHODS: Busulfan pharmacokinetics
      and toxicity were monitored in young rhesus macaques at two dosing levels (4 and
      6 mg/kg). These doses were then employed to condition two animals at each dose
      level prior to autologous transplantation of genetically modified cells using our
      standard methods. RESULTS: Busulfan pharmacokinetic (PK) data showed the area
      under the curve (AUC), drug half-life, and drug clearance were consistent within
      each dose group and similar to those reported in children. Single doses of
      busulfan were well tolerated and produced dose-dependent myelosuppression, most
      notably in the neutrophil and platelet counts. Although marking levels reached
      over 1% early in one animal, the long-term marking was low but detectable at 0.01
      to 0.001%. CONCLUSIONS: We conclude that low-dose intravenous bolus infusion of
      busulfan is well tolerated, has dose-dependent effects on peripheral blood
      counts, and allows long-term engraftment of genetically modified cells, but at
      levels too low for most clinical disorders.

PMID- 16459183
TI  - Ex vivo expansion of G-CSF-mobilized peripheral blood CD133+ progenitor cells on
      coculture with human stromal cells.
AB  - OBJECTIVE: The pentaspan molecule CD133 has been shown to be a marker of more
      primitive hematopoietic progenitors in mobilized peripheral blood (PB). Our
      objective was to assess the efficacy of PB CD133(+) cells in our coculture system
      using human telomerized stromal (HTS) cells. METHODS: Five thousand PB CD133(+)
      cells or conventional cord blood (CB) CD34(+) cells were expanded with or without
      HTS cells in the presence or absence of stem cell factor, thrombopoietin, and Flk
      2/Flt-3 ligand. RESULTS: The coculture was significantly superior in expanding PB
      clonogenic cells as compared with the stroma-free culture (CFU-C, 2 +/- 0 vs 111
      +/- 15-fold of initial cell number, p < 0.01), and the fold increase of PB
      clonogenic cells was comparable to that for CB cells after two weeks of coculture
      (BFU-E, 54 +/- 3 vs 56 +/- 4-fold; CFU-GM, 156 +/- 26 vs 83 +/- 9-fold; CFU-Mix,
      30 +/- 11 vs 80 +/- 36-fold). However, proliferation of CFU-Mk from PB on
      coculture with HTS cells was modest as compared with stroma-free culture.
      Concomitantly, multiple hematopoietic cells transmigrated below the stromal layer
      and formed cobblestone areas (CAs). The production of hematopoietic progenitor
      cells from CAs after coculture with PB was significantly lower than that seen in
      cells cocultured with CB for four weeks (CFU-Mix, 0 +/- 0 vs 9 +/- 5-fold on day
      28, p < 0.01), although a similar number of CAs derived from PB and CB were
      observed. CONCLUSION: PB CD133(+) cells proliferated efficiently above the
      stromal layer, while the characteristics of PB CD133(+) cells underneath the
      human stromal layer were likely to be maintained, even after long-term
      hematopoietic-stromal interaction.

PMID- 16459185
TI  - Hematopoiesis following disruption of the Pitx2 homeodomain gene.
AB  - OBJECTIVE: Study the effect of loss of expression of Pitx2, a homeodomain gene
      preferentially expressed in murine hematopoietic stem/progenitor cells, on
      hematopoietic stem cells (HSCs). METHODS: We examined the fetal livers of mouse
      embryos with homozygous disruption of the Pitx2 gene, using flow cytometry
      immunophenotyping analysis, as well as immunohistochemistry techniques. We
      further investigated the role of Pitx2 in HSCs using a chimeric mouse model
      system. Pitx2 null embryonic stem (ES) cell clones were generated from embryonic
      day 3.5 blastocysts of Pitx2 null embryos. The Pitx2 null donor ES cell
      contribution to the adult hematopoietic system was confirmed by identifying donor
      specific glucose-phosphate isomerase isotype in the erythrocytes using cellulose
      acetate eletrophoresis, and by demonstrating donor-specific major
      histocompatibility complex antigen allotype on the granulocytes/monocytes and T
      and B lymphocytes of the chimeric mice using flow cytometry analysis. RESULTS:
      Pitx2 homozygous null fetal livers are decreased in size and overall cellularity.
      The erythroid cell component of these livers is further reduced as compared to
      that of their wild-type and heterozygous littermates. Detailed quantitative
      analysis of the chimeric mice revealed contribution of Pitx2 null ES cells to
      erythroid, myeloid, lymphoid, and megakaryocytic lineages. The quantitative level
      of ES cell contribution to the peripheral hematopoietic cells was proportional to
      the level of general chimerism as determined by coat color. CONCLUSION: Although
      the fetal livers of Pitx2 null embryos displayed signs of impaired
      erythropoiesis, Pitx2 gene disrupted HSCs can contribute to hematopoiesis under
      physiological conditions.

PMID- 16459184
TI  - Treatment of human bone marrow with recombinant placenta immunoregulator ferritin
      results in myelopoiesis and T-cell suppression through modulation of the cytokine
      chemokine networks.
AB  - OBJECTIVE: Placenta immunomodulator ferritin (PLIF) is a cloned human chimeric
      ferritin H chain with a novel non-ferritin C-terminal 48 amino acid sequence
      (C48). Recombinant PLIF-C48 exhibited cell-mediated immunosuppression. The aim of
      the current study was to investigate the regulatory effects of native placental
      ferritin (PLF), recombinant PLIF, and C48 on hematopoiesis of human bone marrow
      (BM). METHODS: BM mononuclear cells (BM-MNCs) and CD34(+) selected cells were
      treated in vitro with either PLF, PLIF, or C48 without and in combination with
      granulocyte (G)-monocyte (M) colony-stimulating factor (GM-CSF) and subjected to
      hematopoietic progenitor cell assay. Cytokines and chemokines secreted by the
      treated cells were evaluated in culture supernatant using antibody array assays
      to determine mechanism of action. RESULTS: In vitro treatment of BM-MNCs with
      PLF, PLIF, or C48 induced significant growth of myeloid colonies and when mixed
      with GM-CSF or Granulocyte-Colony Stimulating Factor (G-CSF) exhibited additive
      enhanced colony forming units-granulocyte monocyte growth. Yet, C48 treatment of
      selected CD34(+) cells did not yield colony formation and did not affect their
      response to GM-CSF. Treatment of BM-MNCs with C48 for 48 hours induced secretion
      of marked levels of GM-CSF, interleukin (IL)-6, IL-1, and IL-10. These cytokines
      were secreted primarily by C48-treated BM adherent cells and partly by
      nonadherent cells, whereas the CD34(+) selected cells secreted IL-6 only.
      CONCLUSION: C48-PLIF enhancement of myelopoiesis resulted from cross talk between
      BM accessory cells and progenitor cells. The differential PLIF-C48 effects (i.e.,
      myeloid progenitor cell growth and T-cell suppression) are due to their effect on
      the cytokine-chemokine networks.

PMID- 16459186
TI  - Constitutive activation of zebrafish Stat5 expands hematopoietic cell populations
      in vivo.
AB  - OBJECTIVE: Constitutive activation of Stat5 has been observed in a variety of
      malignancies, particularly myeloid leukemias. To directly investigate the in vivo
      consequences of Stat5 perturbation, we expressed constitutively active forms in
      zebrafish. METHODS: We generated mutants of the zebrafish stat5.1 protein (N646H,
      H298R/N714F, and N714F) based on previously identified constitutively active
      mutants of murine Stat5a. The in vitro properties of these mutants were
      determined using phosphorylation-specific antibodies and luciferase reporter
      assays, and their in vivo effects were analyzed through microinjection of
      zebrafish embryos. RESULTS: Two of these stat5.1 mutants (N646H and H298R/N714F)
      showed increased tyrosine phosphorylation and transactivation activity compared
      to the wild-type protein. Expression of either mutant led to a range of
      hematological perturbations, which were more pronounced for the H298R/N714F
      mutant. Interestingly, expression of wild-type also produced generally similar
      phenotypes. Further analysis showed that expression of the H298R/N714F mutant led
      to increased numbers of early and late myeloid cells, erythrocytes, and B cells.
      Some nonhematopoietic developmental perturbations were also observed, but these
      were equally prominent with wild-type or mutant forms. CONCLUSION: These data
      implicate Stat5 activity as a direct critical regulator of hematological cell
      proliferation, suggesting a causal role for constitutively-active Stat5 in the
      etiology of hematological malignancies.

PMID- 16459187
TI  - Tetrahydroxyquinone induces apoptosis of leukemia cells through diminished
      survival signaling.
AB  - OBJECTIVE: Tetrahydroxyquinone is a molecule best known as a primitive
      anticataract drug but is also a highly redox active molecule that can take part
      in a redox cycle with semiquinone radicals, leading to the formation of reactive
      oxygen species (ROS). Its potential as an anticancer drug has not been
      investigated. METHODS: The effects of tetrahydroxyquinone on HL60 leukemia cells
      are investigated using fluorescein-activated cell sorting-dependent detection of
      phosphatidylserine exposure combined with 7-amino-actinomycin D exclusion, via
      Western blotting using phosphospecific antibodies, and by transfection of
      constitutively active protein kinase B. RESULTS: We observe that in HL60 leukemia
      cells tetrahydroxyquinone causes ROS production followed by apoptosis through the
      mitochondrial pathway, whereas cellular physiology of normal human blood
      leukocytes was not affected by tetrahydroxyquinone. The antileukemic effect of
      tetrahydroxyquinone is accompanied by reduced activity of various antiapoptotic
      survival molecules including the protein kinase B pathway. Importantly,
      transfection of protein kinase B into HL60 cells and thus artificially increasing
      protein kinase B activity inhibits tetrahydroxyquinone-dependent cytotoxicity.
      CONCLUSION: Tetrahydroxyquinone provokes cytotoxic effects on leukemia cells by
      reduced protein kinase B-dependent survival signaling followed by apoptosis
      through the mitochondrial pathway. Thus, tetrahydroxyquinone may be
      representative of a novel class of chemotherapeutic drugs, inducing apoptosis in
      cancer cells through diminished survival signaling possibly as a consequence of
      ROS generation.

PMID- 16459188
TI  - Induction of autologous CD4- and CD8-mediated T-cell responses against acute
      lymphocytic leukemia cell line using apoptotic tumor cell-loaded dendritic cells.
AB  - OBJECTIVE: Several studies have demonstrated that dendritic cells (DCs) pulsed
      with tumor lysate or apoptotic tumor cells can elicit effective T-cell responses.
      This technique does not require the identification of the tumor antigen or HLA
      haplotype of the patient. We applied this approach to induce HLA class I- and
      class II-restricted T-cell responses directed against autologous acute
      lymphocytic leukemia (B-ALL) cell line NH-1. METHODS: Autologous T cells were
      stimulated by apoptotic tumor cell-loaded DCs generated from a patient with ALL.
      The stimulated and expanded T cells were isolated into CD8(+) T-cell line and
      CD4(+) T-cell line, and each of them was examined as to their functions. RESULTS:
      Both CD8(+) and CD4(+) T-cell lines demonstrated cytotoxicity against NH-1 in an
      major histocompatibility complex-dependent manner. Finally, we established two
      independent CD4(+) T-cell clones restricted to HLA-DR. The CD4(+) T-cell line
      responded strongly to autologous Epstein-Barr virus-transformed lymphoblastoid
      cell lines (EBV-LCL) but not to autologous normal cells. Furthermore, the T-cell
      clones also responded to allogeneic EBV-LCLs and B-ALL cell lines in the context
      of the HLA-DRB1( *)04051 molecule. Interestingly, 293T and COS-7 cells, which had
      been transfected with the HLA-DRB1( *)04051, were also recognized by T-cell
      clones. CONCLUSION: These findings indicate that B-ALL has shared and strong
      immunogenic epitopes expressed on HLA class II molecules, the expression of which
      is limited to immortalized cells. These data suggest that vaccinations using DCs
      loaded with apoptotic tumor cells might be a potent strategy in the treatment of
      B-ALL.

PMID- 16459189
TI  - Hematopoietic origins of fibroblasts: I. In vivo studies of fibroblasts
      associated with solid tumors.
AB  - OBJECTIVE: Recent studies have reported that bone marrow cells can give rise to
      tissue fibroblasts. However, the bone marrow cell(s) that gives rise to
      fibroblasts has not yet been identified. In the present study, we tested the
      hypothesis that tissue fibroblasts are derived from hematopoietic stem cells
      (HSCs) in vivo. METHODS: These studies were conducted using mice whose
      hematopoiesis had been reconstituted by transplantation of a clonal population of
      cells derived from a single enhanced green fluorescent protein (EGFP)-positive
      HSC in conjunction with murine tumor models. RESULTS: When tumors propagated in
      the transplanted mice were evaluated for the presence of EGFP(+) HSC-derived
      cells, two prominent populations of EGFP(+) cells were found. The first were
      determined to be fibroblasts within the tumor stromal capsule, a subset of which
      expressed type I collagen mRNA and alpha-smooth muscle actin. The second
      population was a perivascular cell associated with the CD31(+) tumor blood
      vessels. CONCLUSION: These in vivo findings establish an HSC origin of
      fibroblasts.

PMID- 16459190
TI  - Hematopoietic origins of fibroblasts: II. In vitro studies of fibroblasts, CFU-F,
      and fibrocytes.
AB  - OBJECTIVE: Using transplantation of a clonal population of cells derived from a
      single hematopoietic stem cell (HSC) of transgenic enhanced green fluorescent
      protein (EGFP) mice, we have documented the hematopoietic origin of
      myofibroblasts, such as kidney mesangial cells and brain microglial cells.
      Because myofibroblasts are thought to be an activated form of fibroblasts, we
      tested the hypothesis that fibroblasts are derived from HSCs. MATERIALS AND
      METHODS: Clones of cells derived from single cells of EGFP Ly-5.2 C57Bl/6 mice
      were transplanted into lethally irradiated Ly-5.1 mice. Using bone marrow and
      peripheral blood cells from mice showing high-level multilineage hematopoietic
      reconstitution, we induced growth of fibroblasts in vitro. RESULTS: Culture of
      EGFP(+) bone marrow cells from clonally engrafted mice revealed adherent cells
      with morphology typical of fibroblasts. Flow cytometric analysis revealed that
      the majority of these cells are CD45(-) and express collagen-I and the collagen
      receptor, discoidin domain receptor 2 (DDR2). Reverse transcriptase polymerase
      chain reaction analysis of cultured cells demonstrated expression of procollagen
      1-alpha1, DDR2, fibronectin, and vimentin mRNA. Fibroblast colonies consisting of
      EGFP(+) cells were observed in cultures of bone marrow cells from clonally
      engrafted mice, indicating an HSC origin of fibroblast colony-forming units.
      Culture of peripheral blood nucleated cells from clonally engrafted mice revealed
      EGFP(+) cells expressing collagen-I and DDR2, indicating that fibrocytes are also
      derived from HSCs. CONCLUSION: We conclude that a population of fibroblasts and
      their precursors are derived from HSCs.

PMID- 16459192
TI  - Neonatal hematopoietic stem cell transplantation cures oc/oc mice from
      osteopetrosis.
AB  - OBJECTIVE: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive
      disorder affecting osteoclast function. Fifty percent of the patients have a
      mutation in the TCIRG1 gene coding for one subunit of an osteoclast proton pump.
      The only curative treatment is hematopoietic stem cell transplantation (SCT). The
      oc/oc mouse has a mutation in the gene homologous to TCIRG1 and its expected
      lifespan is only 3 to 4 weeks. Previous attempts to cure these mice with SCT have
      been unsuccessful. We wanted to determine if early hematopoietic SCT using
      enriched and MHC-matched stem cells can cure oc/oc mice from osteopetrosis.
      METHODS: One- and 8-day-old oc/oc and control mice were radiated with 200, 400,
      or 600 cGy and transplanted intraperitoneally with 1 or 5 x 10(6) normal lineage
      depleted bone marrow cells. Blood, x-ray, and pathology analyses were performed
      on transplanted mice. RESULTS: All 1-day-old mice irradiated with 400 cGy and
      transplanted with 5 x 10(6) cells survived long term. An engraftment level of 20%
      is sufficient to correct most features of the disease. X-ray and histopathology
      examination of transplanted animals showed normalization of bone structure.
      However, although a correction of bone structure occurred, the transplanted oc/oc
      mice were smaller in size than their littermates. In contrast to untreated
      animals, oc/oc mice developed teeth after transplantation, but with abnormal
      structure and shape making them unusable. CONCLUSION: We have shown that this
      murine form of IMO is curable with neonatal SCT using enriched stem cells.

PMID- 16459191
TI  - Bone marrow production of lung cells: the impact of G-CSF, cardiotoxin, graded
      doses of irradiation, and subpopulation phenotype.
AB  - OBJECTIVE: Previous studies have demonstrated the production of various types of
      lung cells from marrow cells under diverse experimental conditions. Our aim was
      to identify some of the variables that influence conversion in the lung. METHODS:
      In separate experiments, mice received various doses of total-body irradiation
      followed by transplantation with whole bone marrow or various subpopulations of
      marrow cells (Lin(-/+), c-kit(-/+), Sca-1(-/+)) from GFP(+) (C57BL/6
      TgN[ACTbEGFP]1Osb) mice. Some were given intramuscular cardiotoxin and/or
      mobilized with granulocyte colony-stimulating factor (G-CSF). RESULTS: The
      production of pulmonary epithelial cells from engrafted bone marrow was
      established utilizing green fluorescent protein (GFP) antibody labeling to rule
      out autofluorescence and deconvolution microscopy to establish the colocaliztion
      of GFP and cytokeratin and the absence of CD45 in lung samples after
      transplantation. More donor-derived lung cells (GFP(+)/CD45(-)) were seen with
      increasing doses of radiation (5.43% of all lung cells, 1200 cGy). In the 900-cGy
      group, 61.43% of GFP(+)/CD45(-) cells were also cytokeratin(+). Mobilization
      further increased GFP(+)/CD45(-) cells to 7.88% in radiation-injured mice. Up to
      1.67% of lung cells were GFP(+)/CD45(-) in radiation-injured mice transplanted
      with Lin(-), c-kit(+), or Sca-1(+) marrow cells. Lin(+), c-kit(-), and Sca-1(-)
      subpopulations did not significantly engraft the lung. CONCLUSIONS: We have
      established that marrow cells are capable of producing pulmonary epithelial cells
      and identified radiation dose and G-CSF mobilization as variables influencing the
      production of lung cells from marrow cells. Furthermore, the putative lung cell
      producing marrow cell has the phenotype of a hematopoietic stem cell.

PMID- 16459193
TI  - The role of age, genotype, sex, and route of acute and chronic administration of
      methylphenidate: a review of its locomotor effects.
AB  - Children with attention deficit hyperactivity disorder (ADHD) are treated for
      extended periods of time with the psychostimulant methylphenidate (MPD). The
      psychostimulants cocaine, amphetamine, and MPD exhibit similar structural
      configuration and pharmacological profile. The consequence of the long-term use
      of psychostimulants such as MPD as treatment for ADHD in the developing brain of
      children is unknown. Repeated treatment with psychostimulants has been shown to
      elicit adverse effects in behavior, such as dependence, paranoia, schizophrenia,
      and behavioral sensitization. Behavioral sensitization and cross-sensitization
      between two drugs are used as experimental markers to determine the potential of
      a drug to develop dependence/addiction. Although there are many reviews written
      about behavioral sensitization involving psychostimulants, scarcely any have
      focused specifically on MPD-elicited behavioral sensitization and cross
      sensitization with other psychostimulants. Moreover, the response to MPD and the
      expression of ADHD vary among females and males and among different populations
      due to genetic variability. Since the interpretation and synthesis of the data
      reported are controversial, this review focuses on the adverse effects of MPD and
      the role of age, sex, and genetic composition on the acute and chronic effects of
      MPD, such as MPD-elicited behavioral sensitization and cross-sensitization with
      amphetamine in animal models. Animal models of drug-induced locomotor
      stimulation, particularly locomotor sensitization, can be used to understand the
      mechanisms underlying human drug-induced dependence.

PMID- 16459194
TI  - Avian influenza and the brain--comments on the occasion of resurrection of the
      Spanish flu virus.
AB  - Recent incidences of direct passage of highly pathogenic avian influenza A virus
      strains of the H5N1 and H7N7 subtypes from birds to man have become a major
      public concern. Although presence of virus in the human brain has not yet been
      reported in deceased patients, these avian influenza subtypes have the propensity
      to invade the brain along cranial nerves to target brainstem and diencephalic
      nuclei following intranasal instillation in mice and ferrets. The associations
      between influenza and psychiatric disturbances in past epidemics are here
      commented upon, and the potentials of influenza to cause nervous system
      dysfunction in experimental infections with a mouse-neuroadapted WSN/33 strain of
      the virus are reviewed. This virus strain is closely related to the Spanish flu
      virus, which is characterized as a uniquely high-virulence strain of the H1N1
      subtype. The Spanish flu virus has recently been reconstructed in the laboratory
      and it passed once, most likely, directly from birds to humans to cause the
      severe 1918-1919 pandemic.

PMID- 16459195
TI  - Diphenyl diselenide and 2,3-dimercaptopropanol increase the PTZ-induced chemical
      seizure and mortality in mice.
AB  - The aim of the present study was to evaluate the interaction between a classic
      GABAergic antagonist -- pentylenetetrazol (PTZ) with an organoselenium compound -
      diphenyl diselenide (PhSe)(2) and with the metal chelating agent -- 2,3
      dimercaptopropanol (BAL). Mice were pre-treated with 150 micromol/kg (PhSe)(2) or
      BAL (250, 500 or 1000 micromol/kg) before treatment with PTZ. Pre-treatment with
      (PhSe)(2) reduced the latency for PTZ-induced seizure at doses of 40 and 60 mg/kg
      and cause a decrease in the latency for PTZ-induced death at the dose of 60
      mg/kg. However, treatment with PTZ at dose of 80 mg/kg was not affected by
      (PhSe)(2) pre-treatment. Pre-treatment with BAL reduced the latency for PTZ
      induced seizure at doses of 40 and 50 mg/kg. In addition, the latency for PTZ
      induced death at the dose of 40 mg/kg was decreased significantly by pre
      treatment with all doses of BAL. At the dose of 50mg/kg, a significant decrease
      in the latency for death occurred only in mice pre-treated with 500 and 1000
      micromol/kg of BAL. Our results indicate that the PTZ-induced chemical seizures
      and mortality was enhanced by (PhSe)(2) and BAL. These results indicated that
      (PhSe)(2) and BAL interact with PTZ possibly by modulating the GABAergic system.

PMID- 16459196
TI  - Effects of early-life stress on behavior and neurosteroid levels in the rat
      hypothalamus and entorhinal cortex.
AB  - Recent evidence support the hypothesis that exposure to stress or trauma during
      early childhood may disturb the formation of functional brain pathways, in
      particular, of the limbic circuits. We examined the effects of exposure to early
      life trauma (juvenile stress) on emotional and cognitive aspects of behavior in
      adulthood as well as on dehydroepiandrosterone (DHEA) and its sulfate ester
      (DHEAS) levels in relevant brain regions. Quantitative assessment of the effects
      of exposure to juvenile stress was made 1 month post-stress, and obtained by
      measuring: emotional (utilizing an open field and a startle response tests) and
      cognitive (Morris water-maze task) functions, as well as neurosteroids
      concentration (DHEA and its sulfate ester, DHEAS) in the hypothalamus and
      entorhinal cortex. We report here that an exposure to juvenile stress led to
      elevated levels of anxiety 1 month post-stress. Moreover, in a spatial learning
      task, the juvenile stress group performed poorer than the control group. Finally,
      an exposure to juvenile stress increased DHEAS but not DHEA concentrations both
      in the hypothalamus and the entorhinal cortex. These findings indicate that an
      exposure to juvenile stress has long-lasting effects on behavior and DHEAS levels
      in the hypothalamus and the entorhinal cortex. These effects may be of relevance
      to our understanding of early life stress-related disorders such as PTSD and
      major depression.

PMID- 16459197
TI  - Melatonin receptor (MT1) knockout mice display depression-like behaviors and
      deficits in sensorimotor gating.
AB  - Although critical for transducing seasonal information, melatonin has also been
      implicated in several physiological systems, as well as the regulation of
      behavioral and cognitive processes. Therefore, we investigated the
      neurobehavioral effects of mice missing the type 1 melatonin receptor (MT1). Male
      and female MT1 knockout (MT1-/-) and wild-type (WT) mice were tested in the
      acoustic startle/prepulse inhibition (PPI), open field and Porsolt forced swim
      tests. Male and female MT1-/- mice displayed dramatically impaired prepulse
      inhibition in the acoustic startle response. Female WT mice were more active in
      the open field than WT males. However, male and female MT1-/- mice did not differ
      in total locomotor activity. WT animals spent significantly more time in the
      center of the arena (a behavioral outcome associated with reduced anxiety-like
      behavior) than MT1-/- mice. Also, the sex difference between male and female WT
      mice in the amount of time spent in the center versus periphery was not observed
      among MT1-/- mice. Both male and female MT1-/- mice significantly increased the
      time spent immobile in the forced swim test, an indication of depressed-like
      behavior. The lifetime lack of MT1 signaling contributes to behavioral
      abnormalities including impairments in sensorimotor gating and increases in
      depressive-like behaviors. Taken together, MT1 receptor signaling may be
      important for normal brain and behavioral function.

PMID- 16459198
TI  - Dorsal raphe nucleus stimulation modulates the response of layers IV and V barrel
      cortical neurons in rat.
AB  - The effect of dorsal raphe nucleus (DRN) electrical stimulation on response
      properties of layers IV and V barrel cortical neurons was studied. To assess the
      receptive field characteristics of cortical neurons, responses of neurons were
      recorded following the displacement of principal and adjacent whiskers
      individually or in a condition test paradigm. Then neuronal responses to the
      displacement of whiskers were analyzed following DRN stimulation at 0, 50, 100,
      200 and 400 ms inter-stimulation intervals. Considering On responses, DRN
      stimulation suppressed the response magnitude of layer V neurons to principal
      whisker deflection, while it slightly increased that of layer IV neurons (not
      statistically significant). The response latency of layer IV neurons increased
      when DRN was stimulated 200 or 400 ms before principal whisker deflection, while
      the response latency of layer V was not changed. DRN stimulation had no effect on
      either magnitude or latency of neuronal response to the adjacent whisker
      deflections. We observed a decrease in the inhibitory effect of the adjacent
      whisker deflection on the magnitude of neuronal response to the principal whisker
      deflection in layer IV when DRN was stimulated 200 ms before the principal
      whisker deflection. Off responses did not show any significant effect of DRN
      stimulation. Our results suggest a modulating role for DRN in processing of the
      incoming information into barrel cortex. This effect might be location dependent.

PMID- 16459199
TI  - Effects of baclofen on reserpine-induced vacuous chewing movements in mice.
AB  - We have described that GABA mimetic drugs present the ability to inhibit the
      expression of reserpine-induced oral movements. In this respect, oral movements
      is associated with important neuropathologies. This study investigates the
      effects of an acute or a repeated treatment of different doses of the GABA(B)
      agonist baclofen, as well as withdrawal from these treatments, on the development
      and/or expression of reserpine-induced vacuous chewing movements (VCM). Male mice
      received two injections of vehicle or of 1mg/kg reserpine separated by 48 h. In
      the first experiment, 24h later, animals were acutely treated with vehicle or
      baclofen (1, 2 or 4 mg/kg). In the second experiment, animals were treated with
      vehicle or baclofen (1 or 4 mg/kg) for four consecutive days receiving a
      concomitant injection of 1mg/kg reserpine (or vehicle) on Days 2 and 4. Twenty
      four hours later, animals received vehicle or baclofen. Thirty minutes after the
      last injection, they were observed for quantification of VCM and open-field
      general activity. The acute administration of all the doses of baclofen abolished
      the manifestation of reserpine-induced VCM. Repeated treatment with 1mg/kg
      baclofen induced tolerance to the ability of an acute injection of this dose to
      reduce VCM. Treatment with baclofen (4 mg/kg) did not modify spontaneous VCM.
      Acute administration of the highest dose induced a decrease in general motor
      activity and a potentiation of the reserpine-induced decrease in general
      activity. These results reinforce the involvement of GABAergic hypofunction in
      the expression of oral movements and suggest that a repeated treatment with
      baclofen induces compensatory changes in GABAergic transmission that can
      attenuate its acute property to decrease VCM.

PMID- 16459200
TI  - Zinc release from Schaffer collaterals and its significance.
AB  - On the basis of the evidence that approximately 45% of Schaffer collateral
      boutons are zinc-positive, zinc release from Schaffer collaterals and its action
      were examined in hippocampal slices. When zinc release from Schaffer collaterals
      was examined using ZnAF-2, a membrane-impermeable zinc indicator, ZnAF-2 signal
      in the stratum radiatum of the CA1 was increased by tetanic stimuli at 100 Hz for
      1s, suggesting that zinc is released from Schaffer collaterals in a calcium- and
      impulse-dependent manner. An in vivo microdialysis experiment indicated that the
      perfusion with 10 microM zinc significantly decreases extracellular glutamate
      concentration in the CA1. When tetanic stimuli at 100 Hz for 5s were delivered to
      the dentate granule cells, the increase in calcium signal in the stratum radiatum
      of the CA1, as well as in the stratum lucidum of the CA3, was attenuated by
      addition of 10 microM zinc, while enhanced by addition of 1mM CaEDTA, a membrane
      impermeable zinc chelator. The increase in calcium signal in the CA1, in which
      Schaffer collateral synapses exist, during delivery of tetanic stimuli at 100 Hz
      for 1s to the Schaffer collateral-commissural pathway was also significantly
      enhanced by addition of 1mM CaEDTA. These results suggest that zinc released from
      Schaffer collaterals suppressively modulates presynaptic and postsynaptic calcium
      signaling in the CA1, followed by the suppression of glutamate release.

PMID- 16459201
TI  - Changes in dopamine and acetylcholine in striatum of the awake rat after chronic
      treatment with a dopamine uptake blocker.
AB  - The effects of chronic treatment with a dopamine uptake blocker on dopamine and
      acetylcholine extracellular concentrations in striatum of the awake rat was
      studied. Male Wistar rats received daily injections (i.p.) of the dopamine uptake
      blocker nomifensine (10 mg/kg) during 22 days. Control group was injected with
      vehicle (saline). Microdialysis experiments were performed on days 1, 8, 15 and
      22 of treatment. Nomifensine injections increased extracellular concentration of
      dopamine in striatum in all days of treatment without differences among days. In
      contrast, acetylcholine levels showed no changes in days 1 and 8 but increased in
      days 15 and 22 of treatment. These results shows that chronic treatment with a
      dopamine uptake inhibitor, nomifensine, has no effects on dopamine release but it
      increases acetylcholine release in striatum of the awake rat. These results would
      help to further understand the effects of chronic dopamine uptake inhibition.

PMID- 16459202
TI  - Only arginine vasopressin, not oxytocin and endogenous opiate peptides, in
      hypothalamic paraventricular nucleus play a role in acupuncture analgesia in the
      rat.
AB  - Our previous study proved that hypothalamic paraventricular nucleus (PVH) plays
      an important role in acupuncture analgesia. The effect of acupuncture on the
      concentrations of arginine vasopressin (AVP), oxytocin (OXT), leucine-enkephaline
      (L-Ek), beta-endorphin (beta-Ep) and dynorphinA(1-13) (DynA(1-13)) was
      investigated in rat PVH. Electrical acupuncture of "Zusanli" points (St. 36) 30
      min increased the AVP, not OXT, L-Ek, beta-Ep and DynA(1-13) concentrations in
      PVH tissue using micropunch and radioimmunoassay, which showed a negative
      relationship between the pain threshold and AVP concentrations in PVH tissue.
      Electrical acupuncture could elevate the AVP concentrations in PVH perfuse liquid
      during acupuncture, and then reduce the AVP concentrations in PVH perfuse liquid
      after acupuncture. But no change in OXT, L-Ek, beta-Ep and DynA(1-13)
      concentrations was detected in PVH perfuse liquid. Electrical acupuncture
      decreased the number of AVP, not OXT, L-Ek, beta-Ep and DynA(1-13) immunoreactive
      cells in PVH using immunocytochemistry. The results suggested that only AVP, not
      OXT and endogenous opiate peptides in PVH involved acupuncture analgesia in the
      rat.

PMID- 16459203
TI  - Transcranial direct current stimulation and the visual cortex.
AB  - Neuroplastic changes are defined as enduring changes in the organization of the
      central nervous system, such as the strength of connections, representational
      patterns, or neuronal properties, either morphological or functional. In recent
      years, new tools have emerged to induce and manipulate ongoing neuroplastic
      changes by external stimulation, either by modification of synchronized neuronal
      activity or modulation of the spontaneous firing rate. The first is performed by
      transcranial magnetic stimulation (TMS), the latter by direct current stimulation
      (tDCS). tDCS as a tool aims to induce prolonged neuronal excitability and
      activity alterations in the human brain via alterations of the neuronal membrane
      potential and results in prolonged synaptic efficacy changes. Apart from its
      impressive persistent excitability effects, it is a non-invasive method and can
      be applied painlessly. Most likely that up- or downregulation of different
      cortical areas by tDCS will open a new branch in the area of visual
      psychophysics.

PMID- 16459204
TI  - Effect of acute versus chronic theophylline administration on acute restraint
      stress-induced increase of pentylenetetrazol seizure threshold in mice.
AB  - Various stressful paradigms were found to induce anticonvulsant effects in
      different seizure models. Methylxanthines, such as theophylline might contribute
      to the reduction of restraint-induced stress. Therefore, in this study the
      influence of acute restraint stress on pentylenetetrazol (PTZ) seizure thresholds
      as well as the effect of acute and chronic theophylline pretreatment on stress
      induced modulation of the seizure threshold were assessed in mice. The onset of
      the three consecutive seizure phases: myoclonic twitch (MTW), generalized clonus
      (GNCL) and tonic hind limb extension (THE) was delayed after exposure to a 2 h
      restraint stress by 34%, 23% and 24%, respectively. In nonstressed mice, acute
      theophylline injection (100 mg/kg, i.p.) decreased the threshold only for THE.
      However, in stressed animals, the pretreatment with the methylxanthine
      significantly enhanced the dose of the convulsant producing the same seizure
      phase. In nonstressed mice, long-term theophylline treatment (50 mg/kg, twice
      daily for 14 days) increased PTZ threshold for all three seizure phases. In
      contrast, in chronically treated with theophylline mice exposed to restraint
      stress, significant decrease in the PTZ threshold for all seizure phases compared
      to control stressed animals have been observed. These results suggest that,
      depending on the treatment regimen (acute versus chronic), theophylline
      specifically and differentially modulates the anticonvulsant effect of restraint
      stress in mice.

PMID- 16459205
TI  - Modulatory role of grape seed extract on age-related oxidative DNA damage in
      central nervous system of rats.
AB  - Aging is the accumulation of diverse deleterious changes in the cells and tissues
      leading to increased risk of diseases. Oxidative stress is considered as a major
      risk factor and contributes to age related increase in DNA oxidation and DNA
      protein cross-links in central nervous system during aging. In the present study,
      we have evaluated the salubrious role of grape seed extract on accumulation of
      oxidative DNA damage products such as 8-OHdG and DNA protein cross-links in aged
      rats. Male albino rats of Wistar strain were divided into four groups: Group I,
      young control rats; Group II, young rats treated with grape seed extract (100
      mg/kg b.wt.) for 30 days; Group III, aged control rats; Group IV, aged rats
      supplemented with grape seed extract (100 mg/kg b.wt.) for 30 days. Our results,
      thus, revealed that grape seed extract has inhibiting effect on the accumulation
      of age-related oxidative DNA damages in spinal cord and in various brain regions
      such as cerebral cortex, striatum and hippocampus.

PMID- 16459206
TI  - Densities of parvalbumin-immunoreactive neurons in non-malformed hippocampal
      sclerosis-temporal neocortex and in cortical dysplasias.
AB  - The changes in density of inhibitory parvalbumin-immunoreactive interneurons were
      quantitatively studied by immunohistochemistry in a series of human neocortical
      samples comprising the spectrum of malformations of cortical development (MCD)
      encountered in epilepsy surgery and the non-malformed hippocampal sclerosis
      temporal neocortex in patients with refractory temporal lobe epilepsy. The
      highest relative density of parvalbumin-immunoreactive cells was obtained in the
      control samples (n = 21). The number of parvalbumin-immunoreactive neurons was
      significantly decreased in non-malformed hippocampal sclerosis-temporal neocortex
      (n = 73, 80.5% of control values). In a proportion of the latter samples as well
      as in two controls we observed patchy regions of absence of parvalbumin staining.
      The total counts of parvalbumin-immunoreactive cells in all the categories of MCD
      - "mild MCD" (n = 25), focal cortical dysplasia type I (n = 19) and type II (n =
      15) - were decreased representing 72.4%, 55.0% and 12.2% of control values,
      respectively. Significantly different parvalbumin-immunoreactive cell densities
      were demonstrated between the focal cortical dysplasia types IIA and IIB. In
      "mild MCD", we observed a more pronounced decrease of parvalbumin-immunoreactive
      cells in the infragranular layers. No significant differences were revealed
      between the temporal and extratemporal examples of analogous MCD types. This
      study provides evidence for reduction of inhibitory parvalbumin-immunoreactive
      interneurons in the epileptic neocortex affected by MCD as well as in
      morphologically unaffected epileptic temporal neocortex, thus representing a
      possible mechanism for their epileptogenicity.

PMID- 16459207
TI  - Diabetes, hypertension, and dyslipidemia in Mexican Americans and non-Hispanic
      whites.
AB  - BACKGROUND: Ethnic disparities in healthcare quality have been documented, but
      knowledge of differences in cardiovascular risk factor prevalence, awareness,
      treatment, and control between Mexican Americans and non-Hispanic whites remains
      incomplete. METHODS: Cross-sectional analysis in 2005 of nationally
      representative data collected from 2256 Mexican-American and 4624 non-Hispanic
      white adults aged 20 years and over who participated in the 1999-2002 National
      Health and Nutrition Examination Survey. RESULTS: Type 2 diabetes is
      significantly more prevalent in Mexican Americans (13% age and gender adjusted)
      than in non-Hispanic whites (8%); however, Mexican Americans are more likely to
      be both diagnosed (77% vs 65%) and treated (63% vs 47%). There is no significant
      difference in the adjusted prevalence of hypertension, at 28% for non-Hispanic
      whites compared to 26% for Mexican Americans. Mexican Americans have a slightly
      lower adjusted prevalence of dyslipidemia, at 31% versus 35%. Awareness of
      hypertension and dyslipidemia are significantly lower in Mexican Americans (57%
      vs 71% for hypertension, and 33% vs 56% for dyslipidemia). Treatment rates for
      hypertension and dyslipidemia are also significantly lower in Mexican Americans
      (42% vs 61% for hypertension; 14% vs 30% for dyslipidemia). Multivariate logistic
      regression controlling for age, gender, education, and access to care indicate
      that Mexican Americans are significantly more likely than non-Hispanic whites to
      be aware and treated for their diabetes, but significantly less likely to be
      aware and treated for their hypertension or dyslipidemia. CONCLUSIONS: The
      significantly higher prevalence of diabetes in Mexican Americans, in contrast to
      hypertension and dyslipidemia, may sensitize healthcare providers to its
      detection and treatment. Communicating the importance of hypertension and
      dyslipidemia is essential for eliminating disparities.

PMID- 16459208
TI  - Influenza vaccination of high-risk children: what the providers say.
AB  - BACKGROUND: Despite a longstanding national recommendation to administer
      influenza vaccine to children at high risk for disease complications, physicians'
      adherence remains low. This study evaluated physicians' perspectives on
      previously documented and persistent under-utilization of influenza vaccine for
      high-risk children. METHODS: A cross-sectional survey mailed in 2001-2002 to a
      nationally representative sample of 1460 U.S. physicians in four key medical
      specialties. The primary outcome was whether the physician provided annual
      influenza vaccine to children with asthma or other cardiopulmonary diseases. The
      hypothesis was that factors predicting reported use would fall into four
      categories: (1) physician knowledge, (2) physician endorsement of recommendation,
      (3) perceived barriers, and (4) practice patterns. RESULTS: The overall response
      rate was 55% (n=600), but differed by specialty. Most physicians were
      knowledgeable about the recommendation, but collectively tended to overestimate
      their own achievements in immunizing high-risk children. Adherence varied by
      physician specialty, endorsement of recommendation, perceived barriers (including
      difficulty identifying subpopulations of high-risk children and confusion about
      who should vaccinate those receiving care from multiple providers), and under
      utilization of strategies known to improve vaccination rates. CONCLUSIONS: Better
      communication strategies are needed to resolve confusion about providing
      influenza vaccine to high-risk children in subspecialty settings. Because of the
      difficulties in selectively identifying high-risk patient subgroups, research is
      needed to assist in putting support strategies into practice. Findings from
      research in promising areas of practice-based quality improvement may be
      particularly applicable.

PMID- 16459210
TI  - Tuberculosis prevention and control in large jails: a challenge to tuberculosis
      elimination.
AB  - BACKGROUND: This study assessed the extent to which 20 large jail systems have
      implemented national recommendations for tuberculosis (TB) prevention and control
      in correctional facilities. METHODS: Data were collected through questionnaires
      to jail medical directors and TB control directors, observation at the jails, and
      abstraction of medical records of inmates with TB disease and latent TB
      infection. RESULTS: Twenty percent of jail systems (4/20) had conducted an
      assessment of risk for TB transmission in their facilities, and 55% (11/20)
      monitored tuberculin skin test conversions of inmates and staff. Sixty-five
      percent (13/20) of jails had an aggregate record-keeping system for tracking TB
      status and treatment, which was usually paper based. Forty-five percent of jails
      (9/20) had policies to offer HIV counseling and testing to tuberculin skin test
      positive patients, and 75% (15/20) screen HIV-infected inmates with chest
      radiographs. Three quarters of jails (15/20) had policies to always isolate
      patients with suspected or confirmed pulmonary TB in an airborne infection
      isolation room. Half of jails with airborne infection isolation rooms (6/12)
      conformed to Centers for Disease Control and Prevention (CDC) guidelines for
      monitoring negative pressure. CONCLUSIONS: Improvements are needed in conducting
      TB risk assessments and evaluations to determine priorities and reduce risk of
      transmission. Inadequate medical information systems are impeding TB control and
      evaluation efforts. Although HIV infection is the greatest cofactor for
      development of TB disease, jails have inadequate information on patients' HIV
      status to make informed decisions in screening and management of TB and latent TB
      infection. Jails need to improve the use of environmental controls.

PMID- 16459209
TI  - Low postpartum rubella vaccination rates in high-risk women, Miami, Florida,
      2001.
AB  - OBJECTIVE: To evaluate adherence to the Advisory Committee on Immunization
      Practices' recommendations on postpartum rubella vaccination in hospitals with a
      high proportion of foreign-born Latina mothers, the highest risk group for
      congenital rubella syndrome. METHODS: In four large hospitals in Miami-Dade
      County, maternal medical records for births in 2001 were randomly selected. Using
      demographic information from birth certificates, vaccination information from
      medical records, and policy information from a hospital survey, postpartum
      rubella vaccination rates were characterized among women eligible for vaccination
      (non-immune and not screened) through univariate and multivariable analyses. Data
      collection was performed in 2002-2003 and the analysis was completed in 2004
      2005. RESULTS: Among 1991 women, 1209 (61%) were foreign born. Overall, 410 (21%)
      were eligible for vaccination, and of these 44 (11%) were vaccinated. Vaccination
      rates were not associated with maternal race/ethnicity or the existence of
      institutional standing-order vaccination policies. A vaccination order was
      recorded for 59% (240/410), but even in the presence of an order, only 17%
      (31/240) of those women were vaccinated. CONCLUSIONS: Despite policies and
      standing orders to vaccinate, postpartum rubella vaccination rates were very low
      among all racial/ethnic subgroups in a sample of hospitals caring for high-risk,
      foreign-born women. These findings suggest that additional system-level
      interventions, such as comprehensive operational guidelines, must accompany
      standing orders to vaccinate rubella non-immune women postpartum.

PMID- 16459212
TI  - CardioVision 2020: program acceptance and progress after 4 years.
AB  - OBJECTIVE: To report program acceptance and progress after 4 years of a heart
      disease prevention program. SUBJECTS: All Olmsted County, Minnesota residents
      aged >/=20 years. METHODS: The analysis is based on independent population-based
      interview samples from 1999, 2000, 2001, and 2003; a dietary questionnaire mailed
      to interviewees; and blood pressure and cholesterol data from medical records of
      consenting Olmsted County residents. National, Minnesota, and Olmsted County
      Behavioral Risk Factor Surveillance System trends for fruit and vegetable
      consumption, body mass index, participation in physical activity, and smoking are
      compared. The data were analyzed in 2005. RESULTS: More than 90% of the
      population considers CardioVision 2020 to be a good, very good, or excellent
      idea. The program is associated with a 25% reduction in the number of people
      exposed to environmental tobacco smoke and small but significant increases in
      consumption of fruits and daily physical activity. The population meeting the
      serum cholesterol goal increased from 52.0% in 1999 to 57.5% in 2003, and the
      population meeting the blood pressure goal increased from 53.7% in 1999 to 59.9%
      in 2003. However, attempts to quit smoking and the amount of time spent in
      physical activity did not increase. By 2003, nearly 9% of the population reported
      making a behavior change because of CardioVision 2020. Compared to Minnesota and
      national trends, fruit and vegetable consumption increased significantly in
      Olmsted County. CONCLUSIONS: The population of Olmsted County views CardioVision
      2020 in a positive light. Positive changes in several personal behaviors and risk
      factor levels have occurred.

PMID- 16459211
TI  - Relationships among dog ownership and leisure-time walking in Western Canadian
      adults.
AB  - BACKGROUND: Dog ownership may be an effective tailored intervention among adults
      for promoting physical activity. This study examined the relationship between
      walking, physical activity levels, and potential psychological mediators between
      people who owned dogs and those who did not own dogs in the Capital Region
      District of Greater Victoria, British Columbia, Canada. Data were collected in
      September 2004; analyses were conducted in January 2005. METHODS: A random sample
      of men (n=177) and women (n=174) aged 20 to 80 years participated. Questionnaires
      were mailed out in 2004 to collect information about demographics, dog ownership,
      leisure-time walking, physical activity levels, and theory of planned behavior
      (TPB) constructs. RESULTS: The analyses revealed that dog owners spent more time
      in mild and moderate physical activities and walked an average of 300 minutes per
      week compared to non-dog owners who walked an average of 168 minutes per week. A
      mediator analysis suggests that dog obligation acts as a mediator between dog
      ownership and physical activity. Moreover, the theory of planned behavior
      constructs of intention and perceived behavioral control explained 13% of the
      variance in walking behavior with an additional 11% variance in walking behavior
      being explained by dog obligation. Regarding intention to walk, the TPB explained
      46% of the variance in intention to walk with dog obligation adding an additional
      1% variance. CONCLUSIONS: In this group of Canadians, those who owned a dog
      participated in more mild to moderate physical activity than those who did not.
      Acquiring a dog should be explored as an intervention to get people more
      physically active.

PMID- 16459213
TI  - The Irvine-Minnesota inventory to measure built environments: development.
AB  - BACKGROUND: Researchers and policymakers increasingly identify active living
      including walking and bicycling for travel and recreation-as a potential strategy
      to increase rates of physical activity in the United States. Understanding the
      impact of the built environment on physical activity levels requires reliable
      methods to measure potentially relevant built environment features. This paper
      presents an audit tool-the Irvine Minnesota Inventory-that was designed to
      measure a wide range of built environment features that are potentially linked to
      active living, especially walking. METHODS: The inventory was created through a
      literature review, focus group interviews, a panel of experts, and field testing
      in 27 settings. The inventory was developed in 2003-2004. RESULTS: The Irvine
      Minnesota Inventory includes 162 items, organized into four domains:
      accessibility (62 items), pleasurability (56 items), perceived safety from
      traffic (31 items), and perceived safety from crime (15 items). (Some items are
      in multiple domains.) The inventory includes both a paper version and a version
      in Microsoft Access, to allow data to be input directly into the computer.
      CONCLUSIONS: Limitations of methods used to develop the inventory are discussed.
      Strategies are offered for using the Irvine Minnesota Inventory to systematically
      and reliably measure characteristics of the built environment that are
      potentially linked to active living.

PMID- 16459214
TI  - The Irvine-Minnesota inventory to measure built environments: reliability tests.
AB  - BACKGROUND: Inter-rater reliability is an important element of environmental
      audit tools. This paper presents results of reliability tests of the Irvine
      Minnesota Inventory, an extensive audit tool aimed at measuring a broad range of
      built environment features that may be linked to active living. METHODS: Inter
      rater reliability was measured by percentage agreement between observers.
      Reliability was tested on a broad range of sites in both California and
      Minnesota. RESULTS: For the variables that remained in the inventory, in tests
      conducted at the University of California-Irvine, 76.8% of the variables had >80%
      agreement among the three raters. In tests conducted at the University of
      Minnesota, 99.2% of the variables had >80% agreement among the two raters.
      CONCLUSIONS: Reliability was high for most items. The inventory was modified to
      eliminate items with low reliability. Differences in the use of the inventory and
      the goals of the research led to generally higher reliability in Minnesota. Those
      differences, limitations, and directions for future research are discussed.

PMID- 16459215
TI  - Is agricultural activity linked to the incidence of human West Nile virus?
AB  - BACKGROUND: West Nile virus (WNV) has spread throughout the contiguous United
      States. During the 2002-2003 period, there were 14,023 laboratory-confirmed human
      cases of WNV in 45 states and 541 associated deaths. Factors that affect case
      distribution are poorly understood. This study assessed the relationship of
      environmental factors and agricultural activity with the presence of human WNV
      cases. METHODS: County-level data were collected that included 2002 and 2003 WNV
      surveillance data, temperature, dairy revenue, precipitation, total irrigated
      acres, and total crop revenue. Logistic regression models were used to determine
      which risk factors were significantly associated with WNV human cases. RESULTS:
      Significant independent predictors for counties with human WNV cases were
      population (odds ratio [OR]=1.20, p<0.0001); higher average daily temperature in
      April through October (OR=1.19 for each additional degree Fahrenheit, p<0.0001);
      and total crop sales (OR=1.14 (p<0.001). The ORs for these predictors increased
      in an analysis of counties with ten or more cases. CONCLUSIONS: Higher
      temperature and farming activity may be strongly associated with the incidence of
      human WNV infection. Larger studies of more agricultural centers are warranted to
      determine which environmental factors increase the risk of human infection and
      how these infections can be prevented.

PMID- 16459216
TI  - Researchers and policymakers: travelers in parallel universes.
AB  - Public policy, in the form of laws, guidelines, and regulations, has a profound
      effect on our daily lives and health status. Reasons for a lack of consistent and
      systematic translation of public health research into public policy is examined,
      including differences in decision-making processes, poor timing, ambiguous
      findings, the need to balance objectivity and advocacy, personal demands of the
      process, information overload, lack of relevant data, and the mismatch of
      randomized thinking with nonrandom problems. Next, several actions are suggested
      that should help bridge the chasm between science and policy, such as greater
      involvement in the process, better understanding of political decision making,
      building of effective teams, and development of political champions. Scientists
      are obligated not only to discover new knowledge but also to ensure that
      discoveries are applied to improve health.

PMID- 16459217
TI  - A tool for measuring physician readiness to manage intimate partner violence.
AB  - BACKGROUND: Intimate partner (domestic) violence (IPV) is a common problem in
      medical practice that is associated with adverse health outcomes. There are
      widespread calls to improve IPV education for physicians, but there are few
      valid, reliable, easily available, and comprehensive measures of physician IPV
      knowledge, attitudes, and practices that can be used to assess training
      effectiveness. METHODS: In 2002, expert consensus and previous surveys were used
      to develop a new survey-based IPV self-assessment tool that included more
      information on current IPV knowledge and practices than previous tools. The draft
      tool was evaluated using standard psychometric techniques in a group of 166
      physicians in 2002, revised, and then retested in a second group of 67 physicians
      on three occasions in 2003 and 2004. Analyses were conducted in 2005. RESULTS:
      The draft IPV survey tool demonstrated good internal consistency reliability,
      with Cronbach's alpha >/=0.65 for ten final scales. The developed scales were
      closely correlated with theoretical constructs and predictive of self-reported
      behaviors. On repeat testing, a revised version of the tool was found to have
      good stability of psychometric properties in a different physician population
      (Cronbach's alpha>/=0.65, and internal correlations as predicted), good
      correlation with measured office IPV practices, and stable results in this
      population over 12 months. CONCLUSIONS: The final version of this instrument,
      named the PREMIS (Physician Readiness to Manage Intimate Partner Violence Survey)
      tool, is a 15-minute survey that is a comprehensive and reliable measure of
      physician preparedness to manage IPV patients. This tool is publicly available
      and can be used to measure the effectiveness of IPV educational programs.

PMID- 16459218
TI  - A community-based trial of an online intimate partner violence CME program.
AB  - BACKGROUND: There is a broad need to improve physician continuing medical
      education (CME) in the management of intimate partner violence (IPV). However,
      there are only a few examples of successful IPV CME programs, and none of these
      are suitable for widespread distribution. DESIGN: Randomized controlled trial
      beginning in September 2003 and ending in November 2004. Data were analyzed in
      2005. SETTING/PARTICIPANTS: Fifty-two primary care physicians in small (fewer
      than eight physicians), community-based medical offices in Arizona and Missouri.
      INTERVENTION: Twenty-three physicians completed a minimum of 4 hours of an
      asynchronous, multi-media, interactive, case-based, online CME program that
      provided them flexibility in constructing their educational experience
      ("constructivism"). Control physicians received no CME. MAIN OUTCOME MEASURES:
      Scores on a standardized self-reported survey, composed of ten scales of IPV
      knowledge, attitudes, beliefs, and self-reported behaviors (KABB) administered
      before randomization and repeated at 6 and 12 months following the CME program.
      RESULTS: Use of the online CME program was associated with a significant
      improvement in eight of ten KABB outcomes, including physician self-efficacy and
      reported IPV management practices, over the study period. These measures did not
      improve in the control group. CONCLUSIONS: The Internet-based CME program was
      clearly effective in improving long-term individual educational outcomes,
      including self-reported IPV practices. This type of CME may be an effective and
      less costly alternative to live IPV training sessions and workshops.

PMID- 16459220
TI  - Occupation medicine: the case for reform.

PMID- 16459221
TI  - Inflammatory mediators and immune function are altered in home parenteral
      nutrition patients.
AB  - OBJECTIVES: Patients who used home parenteral nutrition (HPN) and healthy,
      volunteer control subjects were examined to assess relative immune potential and
      inflammatory marker expression and to investigate the association between HPN and
      immune parameters. METHODS: Subjective Global Assessments were performed on all
      subjects. The peripheral blood concentration of C-reactive protein was determined
      by enzyme-linked immunosorbent assay. The peripheral blood concentration of
      systemic inflammatory mediators that included tumor necrosis factor-alpha (TNF
      alpha), soluble TNF-alpha receptors p55 and p75, and interleukin-6 were similarly
      determined. Peripheral blood lymphocytes were isolated and the percentage of
      circulating CD4+ and CD8+ lymphocytes was determined by flow cytometry. In
      addition, peripheral blood lymphocytes were cultured in the presence of the T
      cell mitogen, phytohemagglutinin, and the proliferative response of the CD3+
      population was assessed by flow cytometry. Results of these experiments were
      obtained for 10 clinically stable patients who had used HPN longer than 2 y and
      these results were compared by Student's t test with data obtained for 12 normal,
      volunteer control subjects. RESULTS: Of the 10 patients who used HPN and were
      examined, seven had short bowel syndrome, two had dysmotility, and one required
      HPN due to radiation enteritis. Based on Subjective Global Assessments, all
      patients were well nourished. No difference was observed in TNF-alpha level
      between groups and C-reactive protein levels were within normal limits (1.2 mg/L
      in patients, 0.99 mg/L in controls). Soluble TNF-alpha receptors p55 and p75 were
      significantly increased (P < 0.001), but serum interleukin-6 was not (P = 0.07).
      The percentage of CD8+ cells and the CD4+/CD8+ ratio were not statistically
      different between groups. In contrast to this result, the percentage of CD4+
      cells and the proliferative T-cell response to phytohemagglutinin were
      significantly depressed in patients who used HPN versus control subjects.
      CONCLUSIONS: These data suggest the presence of an underlying inflammatory
      process and subsequent abnormal T-lymphocyte function in patients who use HPN.

PMID- 16459222
TI  - Effect of a low glycemic index diet with soy protein and phytosterols on CVD risk
      factors in postmenopausal women.
AB  - OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of death in women.
      Hyperlipidemia is a major risk factor for CVD, but research suggests that
      metabolic syndrome and type 2 diabetes are also key factors in CVD in
      postmenopausal women. Most dietary programs, however, focus only on
      hyperlipidemia and not on insulin resistance associated with diabetes and
      metabolic syndrome. This 12-wk trial compared the effects of a dietary program
      combining a low glycemic index diet with a functional food delivering 30 g of soy
      protein and 4 g of phytosterols per day (LGID) with a standard dietary program
      (American Heart Association Step 1 diet; AHAD) in postmenopausal women. METHODS:
      Fifty-nine postmenopausal women (average age 54.6 y, range 44-65 y) with a body
      mass index of 27 to 39 kg/m2 were randomly assigned to the LGID or the AHAD
      program for 12 wk. Total caloric intake and exercise were matched in each arm.
      RESULTS: Twenty-seven women completed the LGID program, and 26 completed the AHAD
      program. The participants on the LGID program showed statistically significant
      decreases in total cholesterol (15.8%, P = 0.0036 between-group comparison), low
      density lipoprotein cholesterol (14.8%, P = 0.004 between-group comparison), and
      triacylglycerol (44.8%, P = 0.006 between-group comparison). In addition,
      significant improvements were observed in ratios of total to high-density
      lipoprotein cholesterol and of triacylglycerol to high-density lipoprotein
      cholesterol, blood pressure, and Framingham risk assessment for coronary heart
      disease compared with the AHAD program. CONCLUSIONS: A significantly greater
      improvement was observed in CVD risk factors in postmenopausal women on the LGID
      program (incorporating 30 g of soy protein and 4 g of phytosterols per day) than
      with a standard therapy.

PMID- 16459224
TI  - Saturated, unsaturated, and trans-fatty acids modulate oxidative burst induced by
      high dextrose in human umbilical vein endothelial cells.
AB  - OBJECTIVE: We determined whether hyperglycemia-induced oxidative burst is
      augmented in the presence of saturated, unsaturated, and trans-fatty acids (FAs).
      METHODS: The time course of superoxide (O2-) production in human umbilical vein
      endothelial cells treated with 5.5 mM (D100) or 27.5 mM (D500) of dextrose and
      select FAs were measured using the hydroethidene fluorescence method. RESULTS:
      The rate of O2- production in cells treated with D500 was significantly higher
      (55% to 125% increase) than the rate observed in control cells treated with D100
      (P < 0.001). The rate of O2- production (mean +/- standard deviation, in
      arbitrary units) was increased when cells were treated with 250, 500, and 1000
      muM of myristic acid (C14; 0.189 +/- 0.04, 0.240 +/- 0.04, 0.234 +/- 0.02,
      respectively; P > 0.1, P < 0.05, P < 0.05, respectively), palmitate (C16; 0.151
      +/- 0.03, 0.218 +/- 0.01, 0.289 +/- 0.07; P > 0.1, P < 0.05, P < 0.01), and
      stearic acid (C18; 0.321 +/- 0.03, 0.259 +/- 0.02, 0.341 +/- 0.03; P < 0.01 for
      all comparisons) compared with control cells treated with D100 only (0.184 +/-
      0.01). In the presence of D500, myristic acid did not significantly augment O2-
      production, whereas stearic acid caused a significant further increase in O2-
      production. The cis unsaturated FA (oleic, C18:1; linoleic, C18:2; or linolenic
      acid, C18:3) stimulated O2- production significantly more than did saturated FA
      or trans-unsaturated FA such as elaidic, linolelaidic, or linolenelaidic acid.
      CONCLUSIONS: Fatty acids have the ability to modulate oxidative load in
      hyperglycemia and this effect may be related to the length, saturation, and
      possibly cis/trans orientation of the FA.

PMID- 16459223
TI  - Vitamin E and C supplementation prevents decrease of eicosapentaenoic acid in
      mononuclear cells in chronic hepatitis C patients during combination therapy of
      interferon alpha-2b and ribavirin.
AB  - OBJECTIVE: We investigated the effects of vitamin E and C supplementation on the
      fatty acid composition of mononuclear cells and on the clinical observations in
      patients who had chronic hepatitis C and received interferon-alpha-2b (IFN-alpha
      2b) and ribavirin combination therapy. METHODS: Patients were randomly allocated
      to receive daily 500 mg of vitamin E and 750 mg of vitamin C (vitamin group, n =
      14) or no supplement (non-vitamin group, n = 16) in addition to IFN-alpha-2b and
      ribavirin therapy. The fatty acid composition of mononuclear cell phospholipids
      was analyzed before and at 2, 4, and 8 wk after treatment. RESULTS: After vitamin
      supplementation, plasma and red blood cell alpha-tocopherol and plasma ascorbic
      acid levels increased in the vitamin group. Serum levels of alanine
      aminotransferase decreased significantly after 2 wk of treatment in both groups.
      At the start of treatment, a lower level of eicosapentaenoic acid (EPA) and a
      higher level of the molar ratio of arachidonic acid to EPA in mononuclear cells
      were observed in the present patients compared with healthy volunteers, and a
      significant correlation between the molar ratio and serum alanine
      aminotransferase level was found. The EPA level of mononuclear cells was
      maintained in the vitamin group during treatment, whereas a significant decrease
      was observed in the non-vitamin group at 4 and 8 wk after treatment. CONCLUSIONS:
      Antioxidant vitamin supplementation during IFN-alpha-2b and ribavirin therapy
      prevented a decrease in EPA of mononuclear cell phospholipids. If a further
      decrease in the ratio of arachidonic acid to EPA can be achieved by using oral
      EPA supplementation, the efficacy of IFN-alpha-2b and ribavirin therapy may be
      improved.

PMID- 16459225
TI  - Dietary diacylglycerol in a typical meal suppresses postprandial increases in
      serum lipid levels compared with dietary triacylglycerol.
AB  - OBJECTIVE: The objective of the present study was to verify the effect of a
      dietary oil, consisting mainly of diacylglycerol (DAG) oil, in a typical meal on
      postprandial changes in serum triacylglycerol (TAG) and remnant-like particle
      cholesterol (RLP-C) compared with dietary triacylglycerol (TAG) oil. METHODS: In
      a double-blind, randomized, crossover design, 43 healthy Japanese men and women
      ingested test meals (2093 kJ of energy, 30 g of protein, 19 g of lipids, and 51 g
      of carbohydrates) containing 10 g of DAG oil (DAG meal) or TAG oil (TAG meal).
      Blood samples were collected in a fasting state (0 h) and at 2, 3, 4, and 6 h
      after ingestion of the meal. RESULTS: Postprandial TAG, RLP-C, and chylomicron
      TAG concentrations were significantly lower after the DAG meal compared with the
      TAG meal. In 29 subjects with fasting serum TAG levels of at least 1.13 mmol/L
      (100 mg/dL), differences in postprandial serum changes between meal types were
      even more remarkable and the incremental areas under the response curve (0 to 6
      h) for serum TAG and RLP-C concentrations after the DAG meal were significantly
      smaller than those after the TAG meal. CONCLUSIONS: These results suggest that
      DAG oil in the daily diet is useful for the prevention of postprandial
      hyperlipidemia and related disorders.

PMID- 16459226
TI  - Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative
      stress, and related quality of life in 12 advanced cancer patients undergoing
      anticancer therapy.
AB  - OBJECTIVE: Fatigue is a multidimensional symptom that is described in terms of
      perceived energy, mental capacity, and psychological status: it can impair daily
      functioning and lead to negative effects on quality of life. It is one of the
      most common side effects of chemotherapy and radiotherapy. In recent studies, l
      carnitine (LC) supplementation has been demonstrated to be able to improve
      fatigue symptoms in patients with cancer. METHODS: In the present study we tested
      the efficacy and safety of LC supplementation in a population of patients who had
      advanced cancer and developed fatigue, high blood levels of reactive oxygen
      species, or both. As outcome measures we evaluated fatigue and quality of life in
      relation to oxidative stress, nutritional status, and laboratory variables,
      mainly levels of reactive oxygen species, glutathione peroxidase, and
      proinflammatory cytokines. From March to July 2004, 12 patients who had advanced
      tumors (50% at stage IV) at different sites were enrolled (male-to-female ratio
      2:10, mean age 60 y, range 42-73). Patients were only slightly anemic (hemoglobin
      10.9 g/dL) and hemoglobin levels did not change after treatment. LC was
      administered orally at 6 g/d for 4 wk. All patients underwent antineoplastic
      treatment during LC supplementation. RESULTS: Fatigue, as measured by the
      Multidimensional Fatigue Symptom Inventory-Short Form, decreased significantly,
      particularly for the General and Physical scales, and for quality of life in each
      subscale of quality of life in relation to oxidative stress. Nutritional
      variables (lean body mass and appetite) increased significantly after LC
      supplementation. Levels of reactive oxygen species decreased and glutathione
      peroxidase increased but not significantly. Proinflammatory cytokines did not
      change significantly. CONCLUSION: Improvement of symptoms with respect to fatigue
      and quality of life in relation to oxidative stress may be explained mainly by an
      increase in lean body mass, which may be considered the most important
      nutritional or functional parameter in assessing the cachectic state of patients.
      In this view, fatigue with related symptoms can well be considered an important
      constituent of cancer-related anorexia cachexia syndrome.

PMID- 16459227
TI  - Interactions of high amylose starch and deoxycholic acid on gut functions in
      rats.
AB  - OBJECTIVE: This study evaluated whether high amylose cornstarch (HAS) could
      prevent adverse physiologic effects induced by deoxycholic acid (DCA) in the gut
      of rats. METHODS: Thirty-two male Sprague-Dawley rats were provided with a low
      amylose cornstarch (LAS) diet or a 50/50 mixture of LAS and HAS diets for 4 wk;
      each of these diets was supplemented with 0 or 2 g of DCA per kilogram of diet.
      Therefore, there were four groups. RESULTS: Cecal content pH was lower in rats
      fed the HAS diets compared with rats fed the LAS diets (P < 0.05). Bifidobacteria
      number in cecal contents, cecal pools of acetate, butyrate, and total short-chain
      fatty acids were highest in rats fed the HAS diet; moreover, the HAS/DCA diet
      resulted in increased Bifidobacteria growth and short-chain fatty acid production
      numerically compared with the LAS/DCA diets (P = 0.06). Production of
      prostaglandin-E2 in colonic mucosa was highest in rats fed the LAS/DCA diet, and
      the intake of HAS significantly decreased prostaglandin-E2 levels (P < 0.05).
      CONCLUSIONS: In this study, DCA may have inhibited fermentation in the large
      intestine and increased prostaglandin-E2 production, and concurrent
      administration of HAS and DCA may have decreased the adverse effects on the gut
      induced by DCA.

PMID- 16459228
TI  - Effects of protein malnutrition on oxidative status in rat brain.
AB  - OBJECTIVES: This study evaluated the effects of protein malnutrition on oxidative
      status in rat brain areas. METHODS: We investigated various parameters of
      oxidative status, free radical content (dichlorofluorescein formation), indexes
      of damage to lipid (thiobarbituric acid-reactive substances assay), and protein
      damage (tryptophan and tyrosine content) in addition to total antioxidant
      reactivity levels and antioxidant enzyme activities of superoxide dismutase,
      glutathione peroxidase, and catalase in different cerebral regions (cortex,
      hippocampus, and cerebellum) from rats subjected to prenatal and postnatal
      protein malnutrition (control 25% casein and protein malnutrition 7% casein).
      RESULTS: Protein malnutrition altered various parameters of oxidative stress,
      especially damage to macromolecules. Free radical content was unchanged by
      protein malnutrition. There was an increase in levels of thiobarbituric acid
      reactive substances, the index of lipid peroxidation, in the cerebellum and
      cerebral cortex (P < 0.05) from protein-malnourished rats. Moreover, significant
      decreases in tryptophan and tyrosine in all tested brain structures (P < 0.05)
      were observed. Catalase activity was significantly decreased in the cerebellum (P
      < 0.05). In addition, a significant decrease in total antioxidant reactivity
      levels (P < 0.05) was observed in the cerebral cortex from protein-malnourished
      rats. CONCLUSIONS: The present data indicated that protein malnutrition increased
      oxidative damage to lipids and proteins from the studied brain areas. These
      results may be an indication of an important mechanism for changes in brain
      development that are caused by protein malnutrition.

PMID- 16459229
TI  - High protein buckwheat flour suppresses hypercholesterolemia in rats and
      gallstone formation in mice by hypercholesterolemic diet and body fat in rats
      because of its low protein digestibility.
AB  - OBJECTIVE: This study evaluated the physiologic properties of high protein
      buckwheat flour (PBF) by examining its effects on serum cholesterol and body fat
      in rats and on cholesterol gallstone formation in mice. METHODS: Animals were fed
      experimental diets that contained casein, buckwheat protein extract (BWP), or PBF
      as a protein source (net protein content 200 g/kg). RESULTS: In experiment 1,
      consumption of PBF and BWP for 10 d caused 33% and 31% decreases, respectively,
      in serum cholesterol of rats fed cholesterol-enriched diets when compared with
      consumption of casein (P < 0.05). Dietary PBF caused a significant decrease in
      liver cholesterol, whereas dietary BWP caused only a slight decrease (P > 0.05).
      Fecal excretion of neutral and acidic steroids in the PBF group was significantly
      higher than those in the BWP and casein groups. In experiment 2, consumption of
      PBF for 10 d significantly suppressed adipose tissue weight and hepatic activity
      of fatty acid synthase in rats fed cholesterol-free diets compared with
      consumption of casein (P < 0.05), whereas that of BWP for this period caused only
      a slight decrease in adipose tissue weight (P > 0.05). In experiment 3, dietary
      PBF and BWP significantly decreased the incidence of cholesterol gallstones and
      lithogenic index in mice fed cholesterol-enriched diets for 27 d, which was
      associated with increased fecal excretion of acidic steroids. CONCLUSION: This
      study demonstrated that PBF has strong activities against hypercholesterolemia,
      obesity, and gallstone formation, suggesting a potential usefulness of PBF as
      functional ingredient.

PMID- 16459230
TI  - Dose-dependent cholesterol-lowering effect of a mayonnaise-type product with a
      main component of diacylglycerol-containing plant sterol esters.
AB  - OBJECTIVE: The objective of this study was to investigate the effective dose of
      plant sterol ester (PSE)-enriched diacylglycerol (DAG) oil for healthy subjects
      with mild hypercholesterolemia. METHODS: A randomized, placebo-controlled, double
      blind, parallel study was performed in patients with mild hypercholesterolemia;
      0.0, 0.3, 0.4, and 0.5 g of PSE was dissolved in 15 g of a DAG-containing
      mayonnaise-type product; and 15 g/d of the product was administered 4 wk.
      RESULTS: Total serum cholesterol levels were significantly decreased as a result
      of the ingestion of at least 0.4 g/d of PSE, and serum low-density lipoprotein
      cholesterol levels were significantly decreased by the ingestion of at least 0.3
      g/d of PSE. CONCLUSIONS: Daily ingestion of 15 g of DAG plus mayonnaise
      containing at least 0.4 g/d of PSE for 4 wk may significantly decrease
      cholesterol.

PMID- 16459231
TI  - Effects of probiotics on radiation-induced intestinal injury in rats.
AB  - OBJECTIVE: Radiotherapy is an important aspect of multimodal cancer therapy, but
      radiation-induced acute intestinal injury is a common and serious problem.
      Disruption of morphologic mucosal integrity and normal bacterial microflora after
      abdominal radiation leads to malabsorption and bacterial translocation. METHODS:
      Lactobacillus bulgaricus strain isolated from yogurt was given as a probiotic to
      rats subjected to radiotherapy. On postradiation day 8 rats were killed.
      Mesenteric lymph nodes, liver, and spleen were excised for microbiologic
      examinations. Segments of jejunum, ileum, and colon were evaluated for the
      presence of inflammation, vascularity, and mucus cells. RESULTS: The results of
      this study suggest that probiotics may have a protective effect on intestinal
      mucosa. CONCLUSION: Probiotics added as substrates can be given by an oral or
      enteral route to patients who undergo radiotherapy to prevent radiation-induced
      enteritis and related malnutrition.

PMID- 16459232
TI  - Lipid profile of rats fed high-fat diets based on flaxseed, peanut, trout, or
      chicken skin.
AB  - OBJECTIVE: Dietary saturated fatty acids are associated with coronary disease.
      Conversely, dietary monounsaturated polyunsaturated fatty acids (MUFAs) and
      polyunsaturated fatty acids (PUFAs) seem to exert a protective effect. This study
      evaluated the lipid profile of rats fed high-fat (HF) diets, with fat added as
      different sources of PUFA (flaxseed and trout), MUFA (peanut), and saturated
      fatty acid (chicken skin). METHODS: Adult male Wistar rats were placed into six
      dietary groups (n = 10): control (normal); high fat, with 1% cholesterol, 10% soy
      oil, and 5% lard; and four groups fed similar HF diets, with 10% lipid as trout,
      flaxseed, peanut, or chicken skin. After 28 d the animals were killed. Blood,
      livers, and adipose tissue samples were collected. RESULTS: A higher level (P <
      0.05) of total serum cholesterol was observed in rats fed the normal diet (93.57
      +/- 14.95 mg/dL) compared with those fed the HF diet (67.57 +/- 12.54 mg/dL).
      Total cholesterol levels in rats fed the flaxseed diet were lower (P < 0.05) than
      in rats fed the other fats. No difference was observed in cholesterol levels
      between groups fed the peanut and chicken skin diets (P > 0.05). Animals fed the
      peanut diet showed decreased body weight gain than did animals in the other
      treatment groups. There were large lipid and cholesterol depositions in livers of
      rats fed the HF diet. Lipid deposition in adipose tissue followed the same
      dietary fatty acid profile, i.e., high levels of omega-3 PUFA in the flaxseed
      group, high levels of MUFA in the peanut and chicken skin groups and high levels
      of omega-6 PUFA in the trout group. CONCLUSIONS: These data indicate that
      flaxseed is promising for dietary manipulation of hyperlipidemia.

PMID- 16459233
TI  - Myocardial infarction: a catabolic disease?

PMID- 16459234
TI  - Duodenal perforation caused by a transpyloric tube in a critically ill infant.
AB  - OBJECTIVE: We describe the case of a 2-mo-old infant who weighed 3.5 kg, had
      alveolar interstitial pneumopathy on mechanical ventilation, and developed a
      duodenal perforation due to a 6-Fr polyurethane transpyloric tube. METHODS AND
      RESULTS: Abdominal ultrasound showed the tube to be within the intestinal lumen.
      Due to this diagnostic error, nutrition was administered through the tube and the
      patient developed severe peritonitis. Laparotomy showed a perforation due to the
      transpyloric tube at the level of the union of the second and third portions of
      the duodenum. The perforation was sutured but the patient developed new
      intestinal perforations with severe progressive intestinal damage, leading to
      multiorgan failure and death. CONCLUSIONS: If there is a clinical suspicion of
      intestinal perforation secondary to insertion of a transpyloric tube, the
      position of the tube must be confirmed by radiographic and echographic
      techniques. In case of doubt, the tube should be withdrawn and endoscopic or
      contrast radiographic evaluation must be performed.

PMID- 16459235
TI  - Dietary fiber, mood, and behavior.

PMID- 16459237
TI  - Nutritional indices in cirrhotic patients.

PMID- 16459239
TI  - The biological, functional and personal consequences of stress.

PMID- 16459240
TI  - The HPA and immune axes in stress: the involvement of the serotonergic system.
AB  - The impact of acute and chronic stress on the hypothalamic-pituitary-adrenal
      (HPA) axis is reviewed and evidence presented that corticotrophin releasing
      factor (CRF) is the stress neurotransmitter which plays an important role in the
      activation of the central sympathetic and serotonergic systems. The activity of
      CRF is expressed through specific receptors (CRF 1 and 2) that are antagonistic
      in their actions and widely distributed in the limbic regions of the brain, as
      well as in the hypothalamus, and on immune cells. The mechanism whereby chronic
      stress, via the CRF induced activation of the dorsal raphe nucleus, can induce a
      change in the serotonergic system, involves an increase in the 5HT2A and a
      decrease in the 5HT1A receptor mediated function. Such changes contribute to the
      onset of anxiety and depression. In addition, the hypersecretion of
      glucocorticoids that is associated with chronic stress and depression
      desensitises the central glucocorticoid receptors to the negative feedback
      inhibition of the HPA axis. This indirectly results in the further activation of
      the HPA axis. The rise in pro-inflammatory cytokines that usually accompanies the
      chronic stress response results in a further stimulation of the HPA axis thereby
      adding to the stress response. While CRF would appear to play a pivotal role,
      evidence is provided that simultaneous changes in the serotonergic and
      noradrenergic systems, combined with the activation of peripheral and central
      macrophages that increase the pro-inflammatory cytokine concentrations in the
      brain and blood, also play a critical role in predisposing to anxiety and
      depression. Neurodegenerative changes in the brain that frequently occur in the
      elderly patient with major depression, could result from the activation of
      indoleaminedioxygenase (IDO), a widely distributed enzyme that converts
      tryptophan via the kynenine pathway to for the neurotoxic end product quinolinic
      acid.

PMID- 16459241
TI  - Stress axis dysfunction in schizophrenia.

PMID- 16459243
TI  - Work-related stressors, depression and quality of life in Danish managers.
AB  - BACKGROUND: By use of valid questionnaires to investigate work-related stress and
      distress in Danish managers. METHODS: The survey focused on members of the Danish
      Association of Managers and Executives who no longer were active (former
      managers' group). Acting managers (active managers' group) served as controls.
      Questionnaires measuring stressors at work and general life events were used. For
      the measurement of distress, scales for depression and quality of life were used.
      RESULTS: The Mokken analysis proved the validity of the questionnaires, i.e.
      their summed-up total scores were sufficient statistics. No differences were
      found between former (n = 1,256) and active managers (n = 942) as to life events.
      Approximately 20% of former managers were at risk of depression and 12% had
      developed major depression. Among the specific work-related stressors were role
      overload, lack of team spirit and lack of social support. The percentage of
      active managers at risk of or suffering from major depression did not differ
      significantly from the Danish general population. Approximately 37% of the former
      managers had a decreased well-being. Alcohol use was found to be significantly
      associated with depression. CONCLUSION: The study identified specific work
      related stressors in managers, 12% of whom developed a major depression.

PMID- 16459244
TI  - Stress: the shared common component in major mental illnesses.

PMID- 16459246
TI  - What a psychiatrist needs to know about diabetes.
AB  - Diabetes mellitus is a complex metabolic disorder, caused by defects in insulin
      action and/or insulin production and is defined as a fasting hyperglycaemia of
      >126 mg/dl, with normoglycaemia being > or = 70 and < or = 110 mg/dl. There are
      two main types of diabetes. Type 1 diabetes (around 10% of cases) is an
      autoimmune disease, usually of early onset, in which pancreatic islet beta cells
      that secrete insulin are destroyed. Type 2 diabetes (around 85% of cases) is
      characterised principally by insulin resistance and impaired insulin secretion.
      Heredity and obesity are major risk factors for Type 2 diabetes. Diabetes is
      associated with potentially life-threatening microvascular and macrovascular
      complications caused by elevated serum glucose levels. Treatment of diabetes aims
      at restoring glycaemic control. In Type 1 diabetes, this can be achieved by
      injecting insulin. Oral hypoglycaemic medications that stimulate insulin
      secretion and/or modify glucose metabolism can be used as a first-line treatment
      in Type 2 diabetes mellitus. However, insulin is usually necessary in later
      phases of the disease. Lifestyle changes, such as diet and exercise, are also
      important. Glycaemic control can be measured by fasting blood glucose levels and
      also by glycosylated haemoglobin levels. The latter measure gives an indication
      of glycaemic control over a period of three months, and a reduction in
      glycosylated haemoglobin is the most appropriate treatment goal in the management
      of diabetes.

PMID- 16459242
TI  - Quality of life measures in schizophrenia.
AB  - The recognition of the importance of evaluating the quality of life of patients
      with schizophrenia highlighted the importance of developing appropriate
      instruments. In this paper we review the available quality of life instruments
      focusing on their conceptual framework, structure, administration and
      psychometric properties. First, we address the generic instruments that have been
      validated for schizophrenic populations, namely the World Health Organization
      Quality of Life Assessment (WHOQOL), the Medical Outcome Study (MOS) 36-Item
      Short-Form Health Survey (SF-36) and the EuroQoL-5 Dimensions (EQ-5D). Then, we
      focus on instruments that have been specifically developed for patients with
      schizophrenia and other or severe mentally illness such as the Quality of Life
      Scale (QLS), the Quality of Life Interview (QoLI), the Lancashire Quality of Life
      Profile (LQoLP), the Sevilla Quality of Life Questionnaire (SQLQ), the Personal
      Evaluation of Transitions in Treatment (PETIT), and the Quality of Life
      Questionnaire in Schizophrenia (S-QoL).

PMID- 16459247
TI  - Schizophrenia, antipsychotics and diabetes: Genetic aspects.
AB  - The relatively high comorbidity of type 2 diabetes and schizophrenia may suggest
      a shared biological susceptibility to these two conditions. Family studies have
      demonstrated an increased risk of diabetes in unaffected relatives of patients
      with schizophrenia, consistent with a heritable susceptibility trait. Linkage
      analyses have identified several loci that are associated with schizophrenia and
      some of these, notably those on chromosomes 2p22.1-p13.2 and 6g21-824.1 have also
      been observed in linkage studies in type 2 diabetes. In addition, the dopamine D5
      receptor on chromosome 5 and the tyrosine hydroxylase gene on chromosome 11 have
      both been suggested as candidate genes in schizophrenia and may also be
      implicated in susceptibility to poor glycaemic control. In addition, an increased
      rate of type II diabetes has been observed in some patients treated with
      antipsychotics. Potential neurochemical substrates of this effect include the
      histamine H1 receptor, the 5-HT2C serotonin receptor or the beta3 adrenoreceptor.
      However, the search for a genetic basis to the association between diabetes and
      schizophrenia is still in its infancy, and much further work needs to be
      performed, including the systematic screening of all confirmed susceptibility
      loci and quantitative trait locus mapping of glycaemic control.

PMID- 16459248
TI  - Data on diabetes from the French cohort study in schizophrenia.
AB  - To establish the impact of antipsychotic medication on the incidence of diabetes,
      we have analysed data from the prospective French Cohort study of mortality in
      schizophrenia. This generated a large database of 3470 patients with
      schizophrenia initially enrolled in 1993 for which data collection on comorbidity
      has been collected systematically every three years since. The primary objective
      of the study was to evaluate the mortality rate in the study cohort. From this
      database, the prevalence and incidence of diabetes can be studied. In 1993, nine
      patients in 10 were prescribed conventional antipsychotics and the remainder
      amisulpride and clozapine. Since the introduction of risperidone and olanzapine,
      atypical antipsychotics are now used in one-third of patients. Multiple
      antipsychotic medications are used in many patients, with the exception of those
      receiving clozapine. At inclusion, 2.2% of patients in the study cohort had a
      diagnosis of diabetes. Morbidity rates were higher in females than in males (3.4%
      and 1.6%, respectively) and it was only in females that the standard morbidity
      ratio with respect to the general population was significantly elevated (2.2; 95%
      confidence intervals: 1.6 and 2.9). The prevalence of diabetes in the study
      cohort rose over the course of the study. Multivariate regression analysis was
      performed in order to identify potential determinants of diabetes. For pre
      existing diabetes, four factors were identified: age at first hospitalisation,
      age, obesity and duration of schizophrenia. The same factors with the exception
      of length of illness were identified for the incident cases. There was no
      evidence for an interaction between the class and type of antipsychotic
      medication and risk of treatment emergent diabetes. However, the use of multiple
      antipsychotic treatments makes the individualisation of specific risks associated
      with any other antipsychotic drug impossible.

PMID- 16459249
TI  - Schizophrenia and diabetes: epidemiological data.
AB  - The association of diabetes mellitus and mental illness, in particular,
      schizophrenia, has been remarked upon for over a century. Recent epidemiological
      studies have shown the age- and sex-matched prevalence of diabetes in patients
      with schizophrenia to be 1.5-2 times those in the general population. This
      difference is particularly noticeable in younger patients. The explanation for
      this finding probably resides in both environmental and biological factors.
      Patients with schizophrenia tend to be sedentary and have a poor diet, which are
      both known risk factors for diabetes. However, familial studies have indicated a
      heritable component to the risk of diabetes in patients with schizophrenia. A
      number of biological mechanisms have been proposed to explain this, including
      neuroendocrine changes and neurodevelopmental anomalies, but none are entirely
      satisfactory. In addition, it has been suggested that treatment with
      antipsychotic medication may potentially increase the risk of diabetes and
      account for some of the increased prevalence seen in patients with schizophrenia.
      It has been suggested that different antipsychotic drugs may differ in their
      ability to facilitate the emergence of poor glycaemic control in patients with
      schizophrenia. However, the situation is far from clear and more work is required
      to accurately assess the potential risk associated with different antipsychotic
      drugs.

PMID- 16459250
TI  - Antipsychotics and the risk of diabetes: a general data review.
AB  - Recently, attention has focused on a potential link between schizophrenia and
      diabetes, with speculation that this potential association is stronger in
      patients who are prescribed atypical antipsychotics. Pharmacoepidemiological
      studies can help to evaluate this potential association. Source data on the
      incidence of diabetes in patients treated with antipsychotics is available in the
      FDA MedWatch database, prescription claims databases and other patient
      registries. These data indicate that antipsychotic drugs may increase the risk of
      developing diabetes and that there may be an interaction with age. However,
      current data are insufficient to accurately assess potential differences in the
      risk of diabetes between users of individual antipsychotic medications. In
      addition, antipsychotic treatment-emergent diabetes has several distinct
      features, notably relating to age of onset, gender ratio, rate of deterioration
      of glycaemic control, and independence from initial treatment emergent weight
      gain. Nonetheless, guidelines for the control of risk factors for diabetes
      developed for the general population appear to be applicable to patients with
      schizophrenia.

PMID- 16459251
TI  - Are there specific care requirements for patients with schizophrenia and diabetes
      or with a risk of diabetes?
AB  - An interactive workshop was held to discuss the risk of diabetes in patients with
      schizophrenia, to evaluate the available data concerning how such patients should
      be managed in terms of minimising the risk of diabetes and of optimising their
      care where diabetes to develop. The subjects discussed covered monitoring of risk
      factors, education about lifestyle and the risk of diabetes, patient care and
      treatment options, and interfaces between psychiatry and diabetology. The
      workshop noted that all patients with a diagnosis of schizophrenia had an
      elevated risk of developing diabetes and that this needed to be reflected in the
      follow-up of the patients in order to reduce the chances of the emergence of
      disease. The risk of diabetes is complicated by the presence of other risk
      factors and the intensity of the diabetes prevention programme needs to reflect
      adequately the overall risk. The most important prevention methods relate to
      lifestyle changes that patients with schizophrenia may be spontaneously unlikely
      to adopt and therefore necessitate the implementation of specific education
      measures aimed at patients and their families. The workshop proposed follow-up
      intensities, monitoring procedures and prevention programmes stratified according
      to the risk of developing diabetes. It was not considered that there was
      sufficient data available to orientate treatment choices between individual
      antipsychotic drugs according to the potential risk of developing diabetes.

PMID- 16459252
TI  - Molecular targets.

PMID- 16459254
TI  - Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin
      A receptor.
AB  - The endothelin-A receptor ligand Atrasentan (ABT-627) was radiolabeled by (11)C
      methylaton of the desmethyl precursor in phenolate form. In mice, the highest
      uptake of [(11)C]ABT-627 was in the liver, kidneys and lungs. No significant
      binding was observed in mouse brain or heart. PET studies in a baboon, however,
      showed accumulation in the myocardium and lungs with a tissue/blood equilibrium
      reached at 40 min postinjection. Between 35 and 75 min, the heart/blood and
      lung/blood ratios were 1.72 and 1.31, respectively. Pretreatment with a 0.39
      mg/kg dose of unlabeled ABT-627 inhibited the uptake of the tracer by 53-54% in
      both the myocardium and lungs at 65 min.

PMID- 16459253
TI  - PET Imaging of the AT1 receptor with [11C]KR31173.
AB  - AIM: The goal of this study was to investigate the binding characteristics of
      [(11)C]KR31173 and its applicability for PET studies of the AT(1) receptor
      (AT(1)R). METHODS: Ex vivo biodistribution and pharmacology were tested in mice.
      PET imaging was performed in mice, beagle dogs and a baboon. To assess
      nonspecific binding, PET imaging was performed both before and after pretreatment
      with a potent AT(1)R antagonist. In the baboon, PET imaging was also performed
      with the previously developed radioligand [(11)C]L-159,884 for comparison.
      RESULTS: Ex vivo biodistribution studies in mice showed specific binding rates of
      80-90% in the adrenals, kidneys, lungs and heart. Specific binding was confirmed
      in mice using small animal PET. In dogs, renal cortex tissue concentration at 75
      95 min postinjection (pi) was 63 nCi/ml per millicurie at a specific binding rate
      of 95%. In the baboon renal cortex, tissue activity at 55-75 min pi was 345
      nCi/ml per millicurie. In the baboon the specific binding of [(11)C]KR31173 was
      higher (81%) than the specific binding of [(11)C]L-159,884 (34%). CONCLUSION:
      [(11)C]KR31173 shows accumulation and significant specific binding to the AT(1)R
      in the kidneys of mice, dogs and baboon. These findings suggest that this
      radioligand is suited for imaging the renal cortical AT(1)R in multiple species.

PMID- 16459255
TI  - Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as
      potential SPECT tracers for cyclooxygenase-2 expression.
AB  - Although several COX-2 inhibitors have recently been radiolabeled, their
      potential for imaging COX-2 expression remains unclear. In particular, the
      sulfonamide moiety of COX-2 inhibitors may cause slow blood clearance of the
      radiotracer, due to its affinity for carbonic anhydrase (CA) in erythrocytes.
      Thus, we designed a methyl sulfone-type analogue, 5-(4-iodophenyl)-1-[4
      (methylsulfonyl)phenyl]-3-trifluoromethyl-1H-pyrazole (IMTP). In this study, the
      potential of radioiodinated IMTP was assessed in comparison with a (125)I-labeled
      celecoxib analogue with a sulfonamide moiety ((125)I-IATP). METHODS: The COX
      inhibitory potency was assessed by measuring COX-catalyzed oxidation by hydrogen
      peroxide. The biodistribution of (125)I-IMTP and (125)I-IATP was determined by
      the ex vivo tissue counting method in rats. Distribution of the labeled compounds
      to rat blood cells was measured. RESULTS: The COX-2 inhibitory potency of IMTP
      (IC(50) = 5.16 microM) and IATP (IC(50) = 8.20 microM) was higher than that of
      meloxicam (IC(50) = 29.0 microM) and comparable to that of SC-58125 (IC(50) =
      1.36 microM). The IC(50) ratios (COX-1/COX-2) indicated the high isoform
      selectivity of IMTP and IATP for COX-2. Significant levels of (125)I-IMTP and
      (125)I-IATP were observed in the kidneys and the brain (organs known to express
      COX-2). The blood clearance of (125)I-IMTP was much faster than that of (125)I
      IATP. Distribution of (125)I-IATP to blood cells (88.0%) was markedly higher than
      that of (125)I-IMTP (18.1%), which was decreased by CA inhibitors. CONCLUSIONS:
      Our results showed a high inhibitory potency and selectivity of IMTP for COX-2.
      The substitution of a sulfonamide moiety to a methyl sulfone moiety effectively
      improved the blood clearance of the compound, indicating the loss of the cross
      reactivity with CA in (125)I-IMTP. (123)I-IMTP may be a potential SPECT
      radiopharmaceutical for COX-2 expression.

PMID- 16459256
TI  - Acquisition of resistance to antitumor alkylating agent ACNU: a possible target
      of positron emission tomography monitoring.
AB  - Early detection of tumor response to chemotherapy is of great importance for
      appropriate treatment of tumors. In this study, characteristics of two positron
      emission tomography (PET) tracers, [(18)F]2-fluoro-2-deoxy-D-glucose (FDG)
      and[(18)F]3'-fluoro-3'-deoxy-thymidine (FLT), in the early detection of tumor
      cell response as well as tolerance development to chemotherapy was compared using
      rat C6 glioma cells and 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2
      chloroethyl)-3-nitrosoureahydrochloride (ACNU). ACNU is an alkylating agent known
      to induce drug resistance through expression of O(6)-methylguanine
      deoxyribonucleic acid methyl transferase (O(6)-MGMT). We established an ACNU
      resistant C6 glioma cell line (C6/ACNU) and investigated the effect of ACNU on
      the uptake of FLT and FDG. In C6 cells, DNA synthesis presented as
      [(3)H]thymidine ([(3)H]Thd) incorporation into DNA was quickly suppressed by
      ACNU. In C6/ACNU cells, the suppression was recovered promptly, indicating that
      DNA alkylation occurs initially but highly expressed O(6)-MGMT repairs DNA,
      leading to the recovery of DNA synthesis. The patterns of FLT uptake in C6 and
      C6/ACNU were difficult to distinguish in the very early stage of the treatment,
      though it was reported that FLT uptake well correlated with proliferation in
      certain conditions. FDG uptake showed different patterns between the resistant
      and control cells, with significantly decreased uptake in C6 cells and unchanged
      uptake in C6/ACNU cells at 18-24 h after the treatment. Though difficult to be
      directly translated into clinical situation, the present study will provide a
      base to develop an appropriate protocol to assess tumor response to treatment by
      PET and to design effective treatment plans.

PMID- 16459257
TI  - Reduced 125I-meta-iodobenzylguanidine uptake and norepinephrine transporter
      density in the hearts of mice with MPTP-induced parkinsonism.
AB  - Uptake of (123)I-meta-iodobenzylguanidine ((123)I-MIBG) is markedly reduced in
      the hearts of patients with Parkinson's disease. Although the mechanism of this
      reduction is unclear, (12)(5)I-MIBG uptake is similarly reduced in the hearts of
      mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP)-induced
      parkinsonism. Three groups of ten 15-week-old C57BL6 mice received
      intraperitoneal injections of (1) saline (control), (2) 10 mg/kg MPTP or (3) 40
      mg/kg MPTP. After 0.185 MBq of (125)I-MIBG was injected, the percent injected
      dose of (125)I-MIBG per gram of tissue (%ID/g) was determined and cardiac
      concentrations of norepinephrine were measured. Cardiac concentrations of
      norepinephrine transporter (NET) were measured in three groups of twenty 15-week
      old C57BL6 mice receiving these same treatments. The %ID/g in mice receiving 10
      or 40 mg/kg MPTP (5.7 +/- 1.1 and 4.4 +/- 1.2%/g) was significantly lower than
      that in control mice (11.3 +/- 2.2%/g; P < .00001 and P < .0000001,
      respectively). The norepinephrine concentration in mice receiving 10 or 40 mg/kg
      MPTP (7.86 +/- 0.67 x 10(5) and 7.50 +/- 0.89 x 10(5) pg/wet g) was significantly
      lower than that in control mice (9.21 +/- 0.97 x 10(5) pg/wet g; P < .01 and P <
      .001, respectively). The NET density in mice receiving 10 or 40 mg/kg MPTP (81 +/
      12, 61 +/- 7 fmol/mg protein) was significantly lower than that in control mice
      (126 +/- 7 fmol/mg protein; P < .000001 and P < .0000001, respectively). The
      %ID/g of (125)I-MIBG and NET density decreased as the dose of MPTP increased.
      This study clearly shows that reduced cardiac (12)(5)I-MIBG uptake in mice with
      MPTP-induced parkinsonism is closely related to the reduced NET density in
      postganglionic cardiac sympathetic nerve terminals.

PMID- 16459258
TI  - Polymer-peptide conjugates for angiogenesis targeted tumor radiotherapy.
AB  - INTRODUCTION: New methods of delivering radiotherapy to sites of occult or
      disseminated cancer are needed to control the disease and address the failure of
      conventional therapy. Because tumor cells rely on angiogenesis for survival, we
      assessed the effectiveness of beta-emitter radiotherapy delivered by polymer
      peptide conjugates that target tumor neovasculature. This molecularly targeted
      radiation is intended to damage both the endothelial bed and surrounding
      neoplastic cells. METHODS: N-(2-Hydroxypropyl) methacrylamide (HPMA), a
      biocompatible and water-soluble copolymer, was derivatized to incorporate side
      chains for (99m)Tc and (90)Y chelation and was further conjugated to a
      alpha(V)beta(3) integrin-targeting peptide (RGD4C). The HPMA copolymer-RGD4C
      conjugate was characterized by its side-chain contents, in vitro endothelial cell
      adhesion assay and its biodistribution and antitumor effectiveness in a SCID
      mouse xenograft model of human prostate carcinoma. RESULTS: The conjugate
      contained about 16 RGD4C moieties per polymer backbone. Tumor accumulation
      significantly increased (P < .01) over time from 1.05 +/- 0.03 % injected dose
      (%ID)/g tissue at 1 h to 4.32 +/-0.32% at 72 h. The activity in major normal
      tissues significantly decreased (P < .05) during that period. At 21 days, the
      control tumors increased 442% in volume from baseline. In contrast, a 7% and a
      63% decrease of tumor volume were observed for the 100- and 250-microCi (90)Y
      treatment groups, respectively. Histopathological examination revealed increased
      apoptosis in the treated tumors with no acute signs of radiation-induced toxicity
      to other organs. CONCLUSION: This copolymer-peptide conjugate targets tumor
      angiogenic vessels and delivers sufficient radiotherapy to arrest tumor growth.

PMID- 16459259
TI  - [11C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis,
      pharmacological characterization and microPET studies in rats.
AB  - N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a
      highly potent and selective inhibitor of the serotonin transporter (SERT). This
      compound was labeled with carbon-11 by methylation of the S-desmethyl precursor
      10 with [(11)C]methyl iodide to obtain the potential positron emission tomography
      (PET) radioligand [(11)C]SMe-ADAM. The radiochemical yield was 27 +/- 5%, and the
      specific radioactivity was 26-40 GBq/micromol at the end of synthesis. Ex vivo
      and in vivo biodistribution experiments in rats demonstrated a rapid accumulation
      of the radiotracer in brain regions known to be rich in SERT, such as the
      thalamus/hypothalamus region (3.59 +/- 0.41%ID/g at 5 min after injection). The
      specific uptake reached a thalamus to cerebellum ratio of 6.74 +/- 0.95 at 60 min
      postinjection. The [(11)C]SMe-ADAM uptake in the thalamus was significantly
      decreased by pretreatment with fluoxetine to 38 +/- 11% of the control value.
      Furthermore, no metabolites of [(11)C]SMe-ADAM could be detected in the SERT-rich
      regions of the rat brain. It is concluded that [(11)C]SMe-ADAM may be a suitable
      PET ligand for SERT imaging in the living brain.

PMID- 16459260
TI  - Animal-specific positioning molds for registration of repeat imaging studies:
      comparative microPET imaging of F18-labeled fluoro-deoxyglucose and fluoro
      misonidazole in rodent tumors.
AB  - INTRODUCTION: Comparative imaging of multiple radiotracers in the same animal can
      be invaluable in elucidating and validating their respective mechanisms of
      localization. Comparative imaging of PET tracers, particularly in small animals,
      is problematic, however: such tracers must be administered and imaged separately
      because simultaneously imaged positron emitters cannot be separated based on
      energy discrimination. OBJECTIVE: As part of our ongoing development of hypoxia
      imaging radiotracers, the intratumoral distributions of sequentially administered
      F18-fluoro-deoxyglucose (FDG) and the hypoxia tracer F18-fluoromisonidazole
      (FMiso) were compared in rats by registered microPET imaging with positioning of
      each animal in a custom-fabricated whole-body mold. METHODS: Nude rats with a
      hindlimb R3327-AT anaplastic rat prostate tumor xenograft and a hindlimb FaDu
      human squamous cell carcinoma (each up to 20 x 20 x 30 mm in size) were studied.
      Rapid-Foam (Soule Medical, Lutz, FL) was used to fabricate animal-specific molds
      for immobilization and reproducible positioning. Each rat was injected via the
      tail vein with approximately 33 MBq (900 microCi) of FDG and imaged in its mold
      at 1 h postinjection (pi) on the microPET. The next day, each rat was injected
      with approximately 22 MBq (600 microCi) of FMiso and positioned and imaged in its
      mold at approximately 2 h pi. Custom-manufactured germanium-68 rods (10 microCi
      each, 1 x 10 mm) were reproducibly positioned in the mold as fiduciary markers.
      RESULTS: The registered microPET images unambiguously demonstrated grossly
      similar though not identical distributions of FDG and FMiso in the tumors - a
      high-activity rim surrounding a lower-activity core. There were subtle but
      possibly significant differences in the intratumoral distributions of FDG and
      FMiso, however. These may not have been discerned without careful image
      registration. CONCLUSION: Animal-specific molds are inexpensive and
      straightforward to fabricate and use for registration (+/-1 to 2 mm) of
      sequential PET images and may aid image interpretation.

PMID- 16459261
TI  - Reproducibility of intraperitoneal 2-deoxy-2-[18F]-fluoro-D-glucose cerebral
      uptake in rodents through time.
AB  - INTRODUCTION: One strength of small animal imaging is the ability to obtain
      longitudinal measurements within the same animal, effectively reducing the number
      of animals needed and increasing statistical power. However, the variability of
      within-rodent brain glucose uptake after an intraperitoneal injection across an
      extended time has not been measured. METHODS: Small animal imaging with 2-deoxy-2
      [(18)F]-fluoro-D-glucose ((18)FDG) was used to determine the variability of a 50
      min brain (18)FDG uptake following an intraperitoneal injection over time in
      awake male and female Sprague-Dawley rodents. RESULTS: After determining the
      variability of an intraperitoneal injection in the awake rat, we found that
      normalization of brain (18)FDG uptake for (1) injected dose and body weight or
      (2) body weight, plasma glucose concentration and injected dose resulted in a
      coefficient of variation (CV) of 15%. However, if we normalized regional uptake
      to whole brain to compare relative regional changes, the CV was less than 5%.
      Normalized cerebral (18)FDG uptake values were reproducible for a 2-week period
      in young adult animals. After 1 year, both male and female animals had reduced
      whole-brain uptake, as well as reduced regional hippocampal and striatal (18)FDG
      uptake. CONCLUSION: Overall, our results were similar to findings in previous
      rodent and human clinical populations; thus, using a high throughput study with
      intraperitoneal (18)FDG is a promising preclinical model for clinical
      populations. This is particularly relevant for measuring changes in brain
      function after experimental manipulation, such as long-term pharmacological
      administration.

PMID- 16459262
TI  - Preparation of cyclotron-produced 186Re and comparison with reactor-produced
      186Re and generator-produced 188Re for the labeling of bombesin.
AB  - The radioisotopes (186)Re and (188)Re have been extensively investigated for
      various forms of radiotherapy due to their useful and high-abundance beta
      particle emissions, low-abundance and imageable gamma-rays, and chemical
      resemblance to technetium. In addition, (188)Re is available in no-carrier-added
      (NCA) form from long lived W-188 generators, whereas (186)Re can be produced in
      large quantities from reactors, although not in NCA form. However, NCA (186)Re
      can be produced on a cyclotron by a (p,n) reaction on (186)W. The purpose of this
      study was to compare labeling of the peptide bombesin with these three forms of
      rhenium radioisotopes. Cyclotron-produced NCA (186)Re was separated
      radiochemically from enriched (186)W (96.9%) targets using high-purity methyl
      ethyl ketone (MEK). The resulting (186)Re-MEK was then loaded onto a small
      alumina column to separate the resulting NCA (186)Re from any remaining (186)W.
      The experimental levels of impurities associated with (186)Re at the end of the
      separation process were found to be 5.7 x 10(-6) Ci of (182)Re (0.57%, t(1/2) =
      12.7 h) and 1.283 x 10(-5) Ci of (182m)Re (1.28%, t(1/2) = 2.67 days). The
      radionuclidic purity of the separated (186)Re was found to be 99.6%, whereas the
      chemical identity was determined by reversed phase high-performance liquid
      chromatography (RP-HPLC) to be perrhenate ((186)ReO(4)(-)). Generator-produced
      (188)ReO(4)(-) from a (188)W/(188)Re generator (Oak Ridge National Laboratory)
      and CA (186)ReO(4)(-) produced from a (185)Re(n,gamma)(186)Re reaction at the
      University of Missouri Research Reactor (MURR) were used for comparison with the
      NCA (186)Re in subsequent studies. N(3)S-5-Ava-BBN(7-14)NH(2) conjugates provide
      flexibility for designing (186,188)Re-labeled conjugates that retain high in
      vitro and in vivo specificity targeting of GRP receptor-expressing cells. This
      study showed that the N(3)S-5-Ava-BBN(7-14)NH(2) could be labeled with
      (186,188)Re following the preconjugation, postmetallation approach. The
      (186,188)Re(V)O-N(3)S-5-Ava-BBN(7-14)NH(2) complexes were found to form stable
      complexes following the reduction of perrhenate (Re(VII)O(4)(-)) with stannous
      chloride at room temperature, as verified by HPLC and stability studies. The
      radiolabeling yield was found to be >90%. The HPLC chromatograms of (186,188)Re
      N(3)S-5-Ava-BBN(7-14)NH(2) complexes revealed two peaks for each conjugate,
      reflecting the presence of syn- and anti-isomers, which were resolvable by HPLC
      but re-isomerized on separation. The biodistribution studies showed that the
      compounds were excreted through the renal and hepatobiliary systems and
      demonstrated receptor-specific uptake with an average pancreas accumulation of
      8.15% ID/g at 1 h postinjection. Administration of cold BBN effectively blocked
      pancreatic uptake and further reflects the high specificity this conjugate has
      for the GRP receptors. At low levels of radioactivity, radiolysis effects were
      not observed. Scale-up may or may not elicit this effect, particularly for the
      higher energy beta emitter (188)Re. The biodistribution studies demonstrated that
      the CA and NCA (186,188)Re conjugates behaved similarly, raising the question of
      whether NCA (186,188)Re is necessary for specific tumor receptor targeting.

PMID- 16459263
TI  - Is subnanomolar binding affinity required for the in vivo imaging of
      acetylcholinesterase? Studies on 18F-labeled G379.
AB  - Acetylcholinesterase (AChE) is an important cholinergic marker of Alzheimer's
      disease (AD) and shows reduced activity in postmortem AD brain tissues. 1-(4
      Fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-fluoro-2-yl)methyl]piperidine (G379,
      ), an AChE inhibitor with a subnanomolar IC(50) (0.56 nM), was prepared as a
      (18)F-labeled radioligand ([(18)F]) and evaluated in mice. Metabolism studies of
      [(18)F] showed no metabolites in the mouse brain. Tissue distribution studies
      demonstrated its uniform regional distribution in the mouse brain, suggesting
      that this radioligand is not suitable for the in vivo imaging of AChE. This
      result along with reports on radiolabeled N-benzylpiperidine lactam benzisoxazole
      (IC(50) < 1 nM) and other radiolabeled benzylpiperidine derivatives (IC(50) > 1
      nM) suggested that a subnanomolar IC(50) may not be the only important factor in
      determining the suitability of a radioligand for in vivo studies of AChE.

PMID- 16459264
TI  - In vitro evaluation of no carrier added, carrier added and cross-complexed [90Y]
      EDTMP provides evidence for a novel "foreign carrier theory".
AB  - The present study focused on the preparation of novel bone tracers containing
      yttrium as radionuclide or carrier. Moreover, these preparations were
      comparatively evaluated in vitro on the basis of a recently presented pre vivo
      model comprising binding studies on synthetic and human bone powder. It was shown
      that among the therapeutic radionuclides, no carrier added [(90)Y]-EDTMP exceeded
      [(188)Re]-EDTMP while yielding lower binding values than [(153)Sm]-EDTMP.
      Furthermore, the authors investigated the influence of "foreign" carriers added
      to [(90)Y]-EDTMP, [(99m)Tc]-EDTMP and [(111)In]-EDTMP by the method of cross
      complexation. The findings reveal a new paradigm: a carrier more foreign to the
      complexed radionuclide causes a higher binding increase on human bone matrices in
      vitro than a more "related" carrier.

PMID- 16459265
TI  - Antiepidermal growth factor variant III scFv fragment: effect of radioiodination
      method on tumor targeting and normal tissue clearance.
AB  - INTRODUCTION: MR1-1 is a single-chain Fv (scFv) fragment that binds with high
      affinity to epidermal growth factor receptor variant III, which is overexpressed
      on gliomas and other tumors but is not present on normal tissues. The objective
      of this study was to evaluate four different methods for labeling MR1-1 scFv that
      had been previously investigated for the radioiodinating of an intact anti
      epidermal growth factor receptor variant III (anti-EGFRvIII) monoclonal antibody
      (mAb) L8A4. METHODS: The MR1-1 scFv was labeled with (125)I/(131)I using the
      Iodogen method, and was also radiohalogenated with acylation agents bearing
      substituents that were positively charged--N-succinimidyl-3-[*I]iodo-5-pyridine
      carboxylate and N-succinimidyl-4-guanidinomethyl-3-[*I]iodobenzoate ([*I]SGMIB)-
      and negatively charged--N-succinimidyl-3-[*I]iodo-4-phosphonomethylbenzoate
      ([*I]SIPMB). In vitro internalization assays were performed with the
      U87MGDeltaEGFR cell line, and the tissue distribution of the radioiodinated scFv
      fragments was evaluated in athymic mice bearing subcutaneous U87MGDeltaEGFR
      xenografts. RESULTS AND CONCLUSION: As seen previously with the anti-EGFRvIII IgG
      mAb, retention of radioiodine activity in U87MGDeltaEGFR cells in the
      internalization assay was labeling method dependent, with SGMIB and SIPMB
      yielding the most prolonged retention. However, unlike the case with the intact
      mAb, the results of the internalization assays were not predictive of in vivo
      tumor localization capacity of the labeled scFv. Renal activity was dependent on
      the nature of the labeling method. With MR1-1 labeled using SIPMB, kidney uptake
      was highest and most prolonged; catabolism studies indicated that this uptake
      primarily was in the form of epsilon-N-3-[*I]iodo-4-phosphonomethylbenzoyl
      lysine.

PMID- 16459266
TI  - Comparative biodistribution study of the new tumor tracer [123I]-2-iodo-L
      phenylalanine with [123I]-2-iodo-L-tyrosine.
AB  - INTRODUCTION: Both A- and l-type amino acid transport are increased in tumor
      cells relative to normal tissue; these transport systems have been the major
      focus of the development of amino acid tumor tracers to overcome the limitations
      of [(18)F]-fluorodeoxyglucose ((18)F-FDG). The newly developed tracer 2-amino-3
      (2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-l-phenylalanine) showed
      high and specific tumor uptake, slow renal elimination and low brain uptake. We
      compared [(123)I]-2-iodo-L-phenylalanine with 2-amino-3-(4-hydroxy-2
      [(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-L-tyrosine), an L-tyrosine
      analogue that has recently entered clinical trials. METHODS: [(123)I]-2-iodo-L
      phenylalanine and [(123)I]-2-iodo-L-tyrosine were evaluated in rhabdomyosarcoma
      tumor-bearing athymic mice by means of dynamic planar imaging (DPI) and
      dissection. A displacement study with L-phenylalanine was performed to prove the
      specificity of tracer tumor uptake, and kinetic modeling was applied to the DPI
      results. Moreover, the biodistribution of both tracers was compared with that of
      (18)F-FDG. RESULTS: Both [(123)I]-2-iodo-L-phenylalanine and [(123)I]-2-iodo-L
      tyrosine showed fast, high and specific tumor accumulation with no significant
      difference. However, [(123)I]-2-iodo-L-phenylalanine was cleared faster from the
      blood to the bladder in comparison with the tyrosine analogue. Moreover, [(123)I]
      2-iodo-L-phenylalanine tumor uptake equilibrated faster with blood. Dissection
      showed that [(123)I]-2-iodo-L-tyrosine slightly accumulated in the liver, which
      was not the case for the phenylalanine analogue. In contrast to (18)F-FDG, both
      tracers showed low uptake in the heart and normal brain tissue, which is
      advantageous for tumor detection in these organs. CONCLUSIONS: [(123)I]-2-iodo-L
      phenylalanine showed more promising characteristics for oncological imaging as
      compared with [(123)I]-2-iodo-L-tyrosine. The former tracer not only demonstrated
      faster blood clearance but also showed that the tracer uptake in the tumor
      reached its equilibrium with the blood pool activity faster, which led to faster
      and better tumor contrast. Moreover, both tracers could overcome an important
      limitation of (18)F-FDG-its high normal brain uptake.

PMID- 16459267
TI  - Influence of sedation and data acquisition method on tracer uptake in animal
      models: [123I]-2-iodo-L-phenylalanine in pentobarbital-sedated tumor-bearing
      athymic mice.
AB  - OBJECTIVES: To minimize movement artifacts during tracer imaging studies, the
      animals are generally sedated. Although many reports describe the effect of
      barbiturates on brain function, less is published about the general impact on the
      extracerebral metabolism and tracer biodistribution. This report describes the
      influence of pentobarbital on tumor uptake of [(123)I]-2-iodo-L-phenylalanine
      ([(123)I]-2I-L-PA) using dissection and nuclear imaging. METHODS: R1M tumor
      bearing athymic mice were divided into two populations: untreated and
      pentobarbital-treated. Each group was subjected to dynamic and static planar
      imaging and organ dissection after [(123)I]-2I-L-PA injection. Two-compartment
      blood modeling was performed. Analysis of variance (ANOVA), t test and clustered
      boxplot analyses were used to compare the results between the treatment groups
      and between the data acquisition methods. RESULTS: Two-compartment blood modeling
      demonstrated that pentobarbital decreased the elimination velocity and the
      distribution toward the peripheral compartment. Both observations lead to higher
      blood pool and kidney activities after administering pentobarbital. The
      dependence of the differential absorption/differential uptake ratio results on
      the factors organ, method and treatment (3-factor ANOVA) demonstrated that all
      factors had a significant effect. Moreover, a significant effect for method and
      treatment was observed for each individual organ, and the ratio of tumor to
      background showed additionally an ordinal interaction between the latter two
      factors. Although the tumor uptake values were lower when using sedation and
      nuclear imaging, the tumor could still be visualized. CONCLUSIONS: An effect of
      sedation treatment and data acquisition method was demonstrated for 2-iodo
      phenylalanine, currently under development as tumor tracer. It is recommended
      that animal experiments should include quantitative investigation of sedation and
      the data acquisition method.

PMID- 16459268
TI  - Biological evaluation of a technetium-99m-labeled integrated tropane-BAT and its
      piperidine congener as potential dopamine transporter imaging agents.
AB  - INTRODUCTION: Recently, we have reported modification of (99m)Tc-TRODAT-1 by
      integrating the N2S2 metal chelating unit and the tropane skeleton. Results of a
      preliminary biodistribution study in rats were promising with respect to brain
      uptake. The present report deals with the further biological characterization of
      the (99m)Tc-labelled integrated TRODAT derivatives ((99m)Tc-TropaBAT and (99m)Tc
      norchloro-TropaBAT) and with the synthesis and biological evaluation of a novel
      (99m)Tc-labelled piperidine-based derivative ((99m)Tc-PipBAT). METHODS:
      Biodistribution of all radiolabelled complexes was studied in normal mice. A more
      detailed ex vivo intracerebral distribution study of the two (99m)Tc-TropaBAT
      complexes was additionally performed in normal rats. Autoradiography of brain
      sections of normal mice (with or without pretreatment with FP-beta-CIT or
      haloperidol) and rats was performed. Affinity for the dopamine transporter (DAT)
      was also assessed in vitro in the presence or absence of cocaine. RESULTS: Both
      (99m)Tc-TropaBAT complexes show a slightly higher brain uptake than (99m)Tc
      TRODAT-1, but the striatum/cerebellum activity ratio is less favourable.
      Nevertheless, significant striatal uptake was detected after ex vivo
      autoradiography, but this uptake was also observed after pretreatment with FP
      beta-CIT. Unexpectedly, no striatal uptake was detected after in vitro incubation
      of mouse brain sections with the tracer agents. For (99m)Tc-PipBAT, neither brain
      uptake nor in vitro striatal uptake was found. CONCLUSION: Both (99m)Tc-TropaBAT
      complexes exhibit similar diffusion into brain as (99m)Tc-TRODAT-1, and ex vivo
      autoradiography shows significant striatal uptake. However, the inferior
      striatum/cerebellum activity ratio, the striatal uptake in mice pretreated with
      FP-beta-CIT or haloperidol, and the lack of striatal uptake during in vitro
      incubation prove that the DAT is not targeted. Brain uptake disappears when the
      tropane skeleton is replaced by a piperidine ring, and also in this case no
      striatal uptake is found in vitro.

PMID- 16459269
TI  - Evaluation of 99mTc-MAG3-annexin V: influence of the chelate on in vitro and in
      vivo properties in mice.
AB  - We conjugated mercaptoacetyltriglycine (MAG(3)) to rh-annexin V to permit
      radiolabeling with (99m)Tc in an effort to decrease the high kidney and liver
      accumulation observed for (99m)Tc-labeled Hynic-annexin V. The 36-kDa protein was
      conjugated at a 5:1 molar ratio with NHS-MAG(3) in HEPES buffer pH 7.8 at room
      temperature, then quenched with glycine and purified by dialysis. The biopotency
      of the resulting MAG(3)-annexin was similar to that of Hynic-annexin as
      determined by a sensitive red blood cell membrane affinity binding assay and a
      surface plasmon resonance (SPR) assay. The (99m)Tc radiolabeling of MAG(3)
      annexin resulted in radiochemical yields of 90% under mildly basic pH conditions.
      Biodistribution data in normal mice clearly showed a significant decrease in
      kidney and liver uptake at 1 h postinjection for the (99m)Tc MAG(3)-annexin
      compared to the (99m)Tc Hynic-annexin (from 24% ID to 4% ID for the liver, and
      45% ID to 15% ID for the kidneys, respectively). Autoradiography of the kidneys
      showed retention of radioactivity in the collecting tubules following
      administration of both labeled annexins. The (99m)Tc MAG(3)-annexin
      biodistribution was also characterized by a lower retention of radioactivity in
      the whole body, but with small intestine accumulation over fivefold higher than
      observed with (99m)Tc Hynic-annexin. These findings show a definite improvement
      in renal and hepatic clearance of the MAG(3) radioligand. However, due to the
      increased radioactivity uptake in the small intestines, the early in vivo
      detection of ongoing apoptosis in the lower abdomen might be more difficult with
      (99m)Tc MAG(3)-annexin. Nevertheless, (99m)Tc MAG(3)-annexin may be an attractive
      alternative to (99m)Tc Hynic-annexin for the in vivo imaging of
      phosphatidylserine receptors.

PMID- 16459270
TI  - Potential of the FES-hERL PET reporter gene system -- basic evaluation for gene
      therapy monitoring.
AB  - PURPOSE: In vivo reporter genes can be powerful tools in supporting and ensuring
      the success of gene therapy. A careful and rational design of a reporter system
      is essential to realize a noninvasive in vivo reporter gene imaging system
      applicable for humans. We designed a new in vivo reporter gene imaging system
      that uses F-18-labeled estradiol (FES) and human estrogen receptor ligand (hERL)
      binding domain, taking advantage that FES is a radiopharmaceutical already being
      used for human studies with access to a wide range of tissues, including the
      brain, and that hERL lacking DNA binding domain can no longer work as a
      transcription factor, and carried out basic studies to evaluate its potential for
      gene therapy monitoring. METHODS: We constructed a plasmid (pTIER) to coexpress a
      model therapeutic gene and the reporter gene hERL and transfected Cos7 cells and
      examined their uptake of [(3)H]estradiol and FES in culture media. The uptake of
      FES by mouse calf muscle electroporated with pTIER was also tested. RESULTS: The
      cells transfected with pTIER took up the radioligands efficiently and
      specifically in culture media. Also, the mouse calf muscle electroporated with
      pTIER accumulated a higher amount of FES than did the control. CONCLUSION: The
      data indicate that our new reporter gene system seems promising for in vivo
      imaging of gene expression and gene therapy monitoring.

PMID- 16459271
TI  - New approach to fully automated synthesis of sodium [18F]fluoroacetate -- a
      simple and fast method using a commercial synthesizer.
AB  - A simple, rapid and fully automated preparation of sodium [(18)F]fluoroacetate
      has been developed by taking advantage of the similarities between the reaction
      pathways of [(18)F]fluoroacetate and [(18)F]-2-fluoro-deoxyglucose (FDG). The
      automated synthesis of sodium [(18)F]fluoroacetate was achieved with a commercial
      [(18)F]FDG synthesizer, the TRACERlab MX(FDG). The method produced the desired
      compound in a short synthesis time (32 min) and with a high and reproducible
      radiochemical yield (50.2 +/- 4.8%, decay corrected). The radiochemical purity of
      sodium [(18)F]fluoroacetate was greater than 99%.

PMID- 16459272
TI  - Intravenous bolus of ultra-low-dose naloxone added to morphine does not enhance
      analgesia in emergency department patients.
AB  - There is some evidence from in vitro, animal, and postoperative clinical studies
      that low doses of opioid antagonists combined with morphine increase analgesia.
      The theoretical model of this effect posits that ultra-low doses of opioid
      antagonists selectively antagonize excitatory, but not inhibitory, opioid
      receptor-mediated signaling. To determine whether this effect occurs in emergency
      department patients presenting with severe acute pain, we conducted a randomized,
      double-blind placebo-controlled trial to assess the relative analgesic effect of
      morphine administered with 3 different doses of naloxone versus morphine alone.
      Patients received 0.1 mg/kg morphine intravenously (IV) over 2 min plus one of 3
      different doses of naloxone (0.1 ng/kg, 0.01 ng/kg, or 0.001 ng/kg) or normal
      saline. A 0 to 10 numerical rating scale (NRS) was used to measure pain intensity
      at baseline and every 30 min up to 4 hours. One hundred fifty-six patients with a
      median NRS of 10 (IQR: 8-10) were studied. There were no clinically or
      statistically significant differences in the mean pain intensity of patients in
      the 4 treatment groups over the 4-hour study period, nor were there differences
      in the administration of additional analgesics or incidence of side effects.
      PERSPECTIVE: Ultra-low doses of naloxone in the 0.001 ng/kg to 0.1 ng/kg range do
      not enhance the analgesia provided by morphine alone among emergency department
      patients with acute, severe pain. This suggests that naloxone in these doses is
      not an effective adjunct to morphine for control of acute pain.

PMID- 16459273
TI  - A pain management program for chronic cancer-treatment-related pain: a
      preliminary study.
AB  - A large proportion of patients may develop chronic pain following cancer
      treatments such as surgery, radiotherapy, or chemotherapy. These patients can
      experience significant levels of physical and psychological morbidity. Our aim
      was to investigate a cognitive-behavioral pain management program (PMP) for
      cancer patients with chronic treatment-related pain. Thirteen patients (1 man, 12
      women; mean age 52 yrs) completed the study, 9 of whom had a history of breast
      cancer and had received extensive medical treatment, including surgery. A
      combination of physical and psychological techniques were adapted from previous
      work in chronic benign pain and implemented by two therapists. Interventions
      included education, relaxation, exercise training, and goal setting. A variety of
      outcomes were examined to assess general fitness, psychological distress, coping
      success, activities of daily living, and pain report. The median number of
      interventions by each therapist was 10 (4 to 15). Postintervention, there was a
      significant trend toward improvement in many variables, including anxiety and
      depression (P < .01), fitness (walking: P < .05), and coping with pain (P < .01).
      This was a feasibility study and has several limitations. It appears, however,
      that all patients had a positive outcome. Further research is now required to
      assess the effectiveness of this approach. PERSPECTIVE: Results of this
      preliminary study are clinically relevant, as they suggest that a pain management
      program that uses cognitive-behavioral principles is worthy of further
      investigation for patients with chronic cancer-treatment-related pain.

PMID- 16459274
TI  - Partner responses to pain behaviors are associated with depression and activity
      interference among persons with chronic pain and spinal cord injury.
AB  - This study investigated the extent to which psychosocial factors (partner
      responses to pain behaviors, social support) are associated with pain-related
      activity interference and depressive symptom severity among individuals with
      spinal cord injury (SCI) and chronic pain. Seventy adults (45 men, 25 women) with
      SCI and pain and 68 partners completed Part II of the West Haven-Yale
      Multidimensional Pain Inventory, a measure of partner responses to pain
      behaviors. Individuals with SCI and pain also completed the Social Support
      Questionnaire-6, a modified Brief Pain Inventory Pain Interference Scale, and the
      Center for Epidemiological Studies-Depression scale. SCI subject ratings of
      partner responses to pain behaviors, but not partner ratings, were associated
      significantly with pain-related activity interference and depressive symptom
      severity. Negative partner response to pain behaviors explained the most variance
      in these 2 outcome measures. The results provide preliminary support for the
      importance of partner responses to pain behaviors in outcomes of individuals with
      chronic pain and SCI. PERSPECTIVE: Chronic pain is a significant problem for many
      persons with spinal cord injury. In this sample of individuals with spinal cord
      injury and pain, perceived partner negative responses to pain behaviors were
      associated positively with activity interference and depression. Decreasing
      negative partner responses to pain behaviors might be a potentially important
      clinical intervention in this population.

PMID- 16459275
TI  - Formalin injection into knee joints of rats: pharmacologic characterization of a
      deep somatic nociceptive model.
AB  - Formalin (0.25, 0.5, 3, and 5%) injected into the knee joint of rats induced a
      dose-dependent nociception that was featured by 2 phases of intense guarding
      behavior of the affected limb, interposed by a period of quasinormal gait
      (quiescent phase). The guarding behavior during a period of forced gait was
      measured by the total time the paw of the affected limb was not in contact with
      the surface of a revolving cylinder (paw elevation time [PET]). Pretreatment with
      morphine (4 mg/kg, subcutaneously) reduced PET in both nocifensive phases, and
      naloxone (1 mg/kg, subcutaneously) antagonized morphine's effect. The
      cyclooxygenase inhibitor diclofenac (5 mg/kg, intraperitoneal) reduced only the
      second phase of nocifensive responses. A low dose of the benzodiazepine midazolam
      (0.25 mg/kg, intraperitoneal) significantly reduced only the second phase of
      response, but a higher dose (1 mg/kg, intraperitoneal) had no effect. A
      subconvulsant, anxiogenic dose of pentylenetetrazol (30 mg/kg, intraperitoneal)
      also did not affect the PET increase induced by formalin. The antihistamine
      meclizine (2.5 mg/kg, intraperitoneal) caused an increase of the response in the
      second phase, but a higher dose (7.5 mg/kg, intraperitoneal) caused inhibition.
      The peripheral antihistamine loratadine (5 and 10 mg/kg, intraperitoneal) also
      caused an increase of the second phase. Neither antihistamine altered the first
      phase of PET. These results reproduced previous findings with classical
      analgesics in formalin-induced nociception. However, the pronociceptive effect of
      antihistamines, and the antinociceptive effect of midazolam observed here suggest
      that formalin-induced incapacitation introduces new characterists of nociceptive
      system that may complement the study of analgesics. PERSPECTIVES: Anxiety is
      thought to influence pain experience in an opposing manner depending on
      nociception originates in cutaneous or deep somatic/visceral tissues. The present
      formalin-induced nociceptive test may help to predict more reliably the pain
      killing effect of new pharmacologic strategies, with classical or nonclassical
      mechanisms, for the treatment of clinically relevant pains, which are generally
      originated in deep structures.

PMID- 16459276
TI  - Assessment of visceral pain-related pseudo-affective responses to colorectal
      distension in mice by intracolonic manometric recordings.
AB  - Recently, a new manometric method has been proposed to quantify visceromotor
      responses (VMR) to colorectal distension (CRD) in rats. This method is based on
      monitoring pressure changes within the distending balloon during CRD. This study
      assesses the applicability of such a technique to the quantification of VMRs to
      CRD in mice. Electrical activity of the abdominal muscles and pressure changes
      within the distending balloon (mechanical response) were simultaneously recorded
      in conscious mice during CRD (phasic ascending, 10-80 mm Hg, or repetitive, 55 mm
      Hg). There was a clear stimulus-response relationship with a strong correlation
      between electrical and mechanical responses during the ascending (r(2) = 0.899, n
      = 7) or repetitive phasic CRD (r(2) = 0.926, n = 8). Repetitive phasic
      distensions (55 mm Hg) increased the mechanical and electrical responses by 71 +/
      20% and 42 +/- 16%, respectively (pulses 10-12 vs. 1-3; n = 8, both P < .01).
      Atropine (0.5 or 1 mg/kg, subcutaneously) did not affect the mechanical response
      to CRD. The mu-opioid agonist, fentanyl (0.05 mg/kg, subcutaneously), completely
      prevented the sensitizing response associated to repetitive distensions. These
      results show that noninvasive, surgery-free manometry of intracolonic pressure is
      a reliable method to assess VMRs to CRD in mice. The analgesic effect of
      compounds could be determined, indicating that the method can be used in
      pharmacologic studies. PERSPECTIVE: The model presented to assess visceral pain
      in mice allows a broad use of this species in pharmacological studies and will be
      of use in the characterization of potential targets and new drugs for the
      treatment of human pathologies with visceral pain arising from the gut as a
      significant component.

PMID- 16459277
TI  - Economic evaluation of oral treatments for neuropathic pain.
AB  - The effectiveness of amitriptyline, carbamazepine, gabapentin, and tramadol for
      the treatment of neuropathic pain has been demonstrated, but it is unknown which
      one is the most cost-effective. We designed a cost-utility analysis of a
      hypothetical cohort with neuropathic pain of postherpetic or diabetic origin. The
      perspective of the economic evaluation was that of a third-party payor. For
      effectiveness and safety estimates, we performed a systematic review of the
      literature. For direct cost estimates, we used average wholesale prices, and the
      American Medicare and Clinical Laboratory Fee Schedules. For utilities of health
      states, we used the Health Utilities Index. We modeled 1 month of therapy. For
      comparisons among treatments, we estimated incremental cost per utility gained.
      To allow for uncertainty from variations in drug effectiveness, safety, and
      amount of medication needed, we conducted a probabilistic Monte Carlo simulation.
      Amitriptyline was the cheapest strategy, followed by carbamazepine, and both were
      equally beneficial. Gabapentin was the most expensive as well as the least
      beneficial. A multivariable probabilistic simulation produced similar results to
      the base-case scenario. In summary, amitriptyline and carbamazepine are more cost
      effective than tramadol and gabapentin and should be considered as first-line
      treatment for neuropathic pain in patients free of renal or cardiovascular
      disease. PERSPECTIVE: Prescription practices should be based on the best
      available evidence, which includes the evaluation of the medication's cost
      effectiveness. This does not mean that the cheapest or the most expensive, but
      rather the most cost-effective medication should be chosen-the one whose benefits
      are worth the harms and costs. We report a cost-effectiveness evaluation of
      treatments for neuropathic pain.

PMID- 16459278
TI  - Pain interference in persons with spinal cord injury: classification of mild,
      moderate, and severe pain.
AB  - Pain intensity is commonly measured by patient ratings on numerical rating scales
      (NRS). However, grouping such ratings into categories may be useful for guiding
      treatment decisions or interpreting clinical trial outcomes. The purpose of this
      study was to examine pain intensity classification in 2 samples of persons with
      spinal cord injuries (SCI) and chronic pain. The first sample (n = 307) rated the
      average intensity and activity interference of pain in general, and the second
      sample (n = 174) rated their worst pain problem. Pain intensity was categorized
      as mild, moderate, or severe using 4 possible classification systems; analyses
      were performed to determine the classification system that best distinguished the
      pain intensity groups in terms of activity interference. In both samples, the
      optimal mild/moderate boundary was lower (mild = 1-3 on a 0-10 NRS scale) than
      that reported previously for individuals with other pain problems. The
      possibility that pain may interfere with activity at lower levels for individuals
      with SCI requires further exploration. The moderate/severe boundary suggested by
      previous research was confirmed in only one of the samples. Implications for the
      assessment of pain intensity and functioning in persons with SCI and pain are
      discussed. PERSPECTIVE: Although pain in individuals with SCI is common, more
      research is needed regarding its characteristics and treatment. This study sought
      to develop an empirically based classification system for mild, moderate, and
      severe pain that could be useful for applying clinical treatment guidelines and
      for interpreting the results of much-needed clinical trials.

PMID- 16459279
TI  - Pain behaviors produced by capsaicin: influence of inflammatory mediators and
      nerve injury.
AB  - The present study was undertaken to characterize spontaneous (ie, nonevoked) pain
      behaviors (flinching, biting/licking) produced by local injections of capsaicin
      into the rat hindpaw as a model of chemogenic pain, and to determine effects of
      inflammatory mediators and nerve injury on such behaviors. Capsaicin antagonists
      are a potential class of novel topical analgesics, and this model may be of value
      for preclinical screening of novel compounds. Local injections of capsaicin (0.1
      30 microg) into the hindpaw produced flinching and biting/licking behaviors over
      5 min, and these were reduced by capsazepine, a competitive antagonist for
      capsaicin at the TRPV1 receptor. Coadministration of noradrenaline (NA),
      prostaglandin E(2) (PGE(2)), and 5-hydroxytryptamine (5-HT) augmented capsaicin
      evoked responses primarily by extending the duration of behaviors. Partial
      sciatic nerve ligation decreased flinching produced by capsaicin alone, by
      capsaicin in combination with each of NA, PGE(2), and 5-HT, and by formalin.
      Tibial nerve injury also reduced capsaicin-evoked flinching, and responses to
      formalin, but spinal nerve ligation did not affect either. These results indicate
      that (1) spontaneous pain behaviors occur as a result of TRPV1 receptor
      activation with a different time course than evoked responses, (2) inflammatory
      mediators augment capsaicin-evoked pain behaviors, and (3) various forms of nerve
      injury produce different effects on capsaicin-evoked pain behaviors. PERSPECTIVE:
      The VR1 receptor is a potential target for development of novel topical
      analgesics. This study characterized pain behaviors produced by local injections
      of capsaicin in the presence of inflammatory mediators and following various
      forms of nerve injury. Results are of interest for the preclinical screening of
      novel VR1 receptor antagonists.

PMID- 16459280
TI  - Recalled pain ratings: a complex and poorly defined task.
AB  - Self-report ratings of pain intensity are ubiquitous in research and clinical
      practice. In addition to rating their current pain, patients are often asked to
      provide ratings to represent pain intensity over several days or weeks. Few data
      are available that provide insight into how people understand and accomplish this
      recall task. This study describes the results of structured interviews with 106
      rheumatology patients with chronic pain about how they arrived at their ratings
      of pain intensity on a visual analog scale referenced to the past week. Most
      patients were unable to coherently articulate how they derived their ratings.
      Moreover, there was no consistency across patients. A variety of different
      strategies were identified that guided their responses. These results support the
      concern about the meaning and validity of retrospective recall ratings. Recall of
      pain, a seemingly simple task, is a deceptively more complex phenomenon. Efforts
      to improve the measurement of recalled pain need to be explored. Improving
      instructional sets, clearer specification of the dimensions of pain being
      targeted, avoiding use of a single item to measure pain, improved description of
      intended reference groups, and determining the length of time that patients are
      able to remember pain and limiting recall periods are reasonable methods that
      need to be explored. PERSPECTIVE: These results emphasize our lack of a full
      understanding of the meaning of the information elicited by commonly used pain
      recall questions. They point to the potential importance of clearly specifying
      what qualities of pain are sought and how the patient should summarize them over
      the reporting period.

PMID- 16459283
TI  - Creation of the National Institute of Nursing Research: talking the walk for
      nursing research.

PMID- 16459284
TI  - National agenda for advanced practice nursing: the practice doctorate.
AB  - The purpose of this article was to provide the background and rationale for the
      practice doctorate in nursing. The American Association of Colleges of Nursing's
      Position Statement on the Practice Doctorate in Nursing, approved in October
      2004, will be discussed. Outlined are some of the changes that will be needed in
      education, regulation, and advanced practice. Common questions and concerns that
      advanced practice nurses have, including titling, salary, and transitioning to
      the doctor of nursing practice degree, will be addressed.

PMID- 16459285
TI  - Toward a qualified yes: personal characteristics of postbaccalaureate nursing
      students and implementation of the clinical nurse leader role.
AB  - Anecdotal and research data suggest that psychological type and explanatory style
      influence individuals' day-to-day functioning. The assessment of these
      characteristics among postbaccalaureate students will support faculty in planning
      for students' educational programs and guide them as they provide support for the
      expansive role functions of, among others, the graduates of the newly proposed
      clinical nurse leader program. This article is a report of one study included in
      a longitudinal project examining the influence of psychological type and
      explanatory style on students' academic success. The questions addressed in this
      article are as follows: "How do psychological type and explanatory style differ
      between entering baccalaureate students and entering postbaccalaureate students?"
      and "How do experiences of depression and fatigue differ between these two groups
      of novice nursing students?" Findings suggest that postbaccalaureate students,
      although similar in psychological type to baccalaureate students, are
      significantly less depressed, less fatigued, and less positive in explanatory
      style than traditional baccalaureate students, indicating a potential need for
      support in addressing the demands of the roles that they will encounter as
      nurses.

PMID- 16459286
TI  - Student learning with concept mapping of care plans in community-based education.
AB  - Concept mapping, a learning strategy used to understand key concepts and
      relationships between concepts, has been suggested as a method to plan and
      evaluate nursing care. The purpose of this study was to empirically test the
      effectiveness of concept mapping for student learning and the students'
      satisfaction with the strategy. A quasi-experimental pre- and posttest design was
      used to examine the content of concept maps of care plans constructed by junior
      level baccalaureate students (n = 23) at the beginning and end of a community
      based mental health course. Additionally, students completed a questionnaire to
      self-evaluate their learning and report their satisfaction with concept mapping.
      Findings indicated that concept mapping significantly improved students'
      abilities to see patterns and relationships to plan and evaluate nursing care,
      and most students (21/23) expressed satisfaction in using the strategy. This
      study supported concept mapping as an additional learning strategy and has
      extended knowledge in community-based nursing education.

PMID- 16459287
TI  - The relationships among workplace stressors, coping methods, demographic
      characteristics, and health in Australian nurses.
AB  - Nursing is known to be stressful. Stress detrimentally can influence job
      satisfaction, psychological well-being, and physical health. There is a need for
      increased understanding of the stress that nurses experience and how best to
      manage it. Three hundred twenty Australian acute care public hospital nurses
      participated in a study by completing four questionnaires that examined (a) how
      various workplace stressors relate to ways of coping, demographic
      characteristics, and physical and mental health and (b) which workplace
      stressors, coping mechanisms, and demographic characteristics were the best
      predictors of physical and mental health. Significant correlations were found
      between stressors and physical and mental health. Multiple regression showed age
      to be the only significant predictor of physical health. The best coping
      predictors of mental health were escape-avoidance, distancing, and self-control.
      Other significant predictors of mental health were support in the workplace, the
      number of years worked in the unit, and workload. Mental health scores were
      higher for nurses working more years in the unit and for those who used
      distancing as a way of coping. Mental health scores were lower for nurses who
      used escape-avoidance, lacked workplace support, had high workload, and used self
      control coping. The findings have implications for organizational management,
      particularly in terms of recommendations for stress management, social support,
      and workload reduction.

PMID- 16459288
TI  - Characteristics of medication errors made by students during the administration
      phase: a descriptive study.
AB  - Faculty concentrate on teaching nursing students about safe medication
      administration practices and on challenging them to develop skills for
      calculating drug dose and intravenous flow rate problems. In spite of these
      efforts, students make medication errors and little is known about the attributes
      of these errors. Therefore, this descriptive, retrospective, secondary analysis
      study examined the characteristics of medication errors made by nursing students
      during the administration phase of the medication use process as reported to the
      MEDMARX, a database operated by the United States Pharmacopeia through the
      Patient Safety Program. Fewer than 3% of 1,305 student-made medication errors
      occurring in the administration process resulted in patient harm. Most were
      omission errors, followed by errors of giving the wrong dose (amount) of a drug.
      The most prevalent cause of the errors was students' performance deficits,
      whereas inexperience and distractions were leading contributing factors. The
      antimicrobial therapeutic class of drugs and the 10 subcategories within this
      class were the most commonly reported medications involved. Insulin was the
      highest-frequency single medication reported. Overall, this study shows that
      students' administration errors may be more frequent than suspected. Faculty
      might consider curriculum revisions that incorporate medication use safety
      throughout each course in nursing major courses.

PMID- 16459289
TI  - Computer literacy study: report of qualitative findings.
AB  - Computer literacy and information literacy are critical to the future of nursing.
      The very nature of health care is being transformed in response to environmental
      drivers such as the demands for cost-effective delivery of high quality services
      and enhanced patient safety. Facilitating the quality transformation depends on
      strategic changes such as implementing evidence-based practice (), promoting
      outcome research (), initiating interdisciplinary care coordination [Zwarenstein,
      M., Bryant, W. (2004). Interventions to promote collaboration between nurses and
      doctors. The Cochrane Library(I)], and implementing electronic health records ().
      Information management serves as a central premise of each of these strategies
      and is an essential tool to facilitate change. This report of the analysis of
      qualitative data from a national online survey of baccalaureate nursing education
      programs describes the current level of integration of the computer literacy and
      information literacy skills and competencies of nursing faculty, clinicians, and
      students in the United States. The outcomes of the study are important to guide
      curriculum development in meeting the changing health care environmental demands
      for quality, cost-effectiveness, and safety.

PMID- 16459290
TI  - Validating the Interpersonal Communication Assessment Scale.
AB  - Despite the centrality of interpersonal communication in nursing, there are few
      psychometrically sound instruments to measure the communication competencies of
      undergraduate and graduate nursing students. This article reports on the
      development and testing of the Interpersonal Communication Assessment Scale
      (ICAS), which was designed to assess the communication competencies of students
      in undergraduate and graduate nursing programs. Retroductive triangulation, using
      both deductive and inductive methods, and the Model of Relational Competence
      guided the measure's conceptualization and development. We used responses from
      531 (24%) undergraduate and graduate clinical faculty from 246 American
      Association of Colleges of Nursing member schools for the psychometric testing of
      the 54-item content-validated and pilot-tested ICAS. Exploratory-factor analysis
      resulted in a three-factor solution labeled as advocacy, therapeutic use of self,
      and validation. These factors accounted for 60% of the variance. Items that
      loaded .60 or higher were retained, resulting in a 23-item scale with a
      Cronbach's alpha of .96. The ICAS significantly differentiated the communication
      competencies of beginning and graduating students in both undergraduate and
      graduate programs. The ICAS was found to have construct validity and internal
      consistency, underscoring its potential as a formative and summative tool to
      assess the interpersonal communication competencies of nursing students.

PMID- 16459291
TI  - Open sesame! Coxsackieviruses conspire to trespass the tight junctional gate.
AB  - In the January 13 issue of Cell, Coyne and Bergelson describe an "Open sesame!"
      strategy developed by coxsackieviruses to invade the organism through the
      intestinal epithelium. The strategy involves coopting intrinsic signaling
      abilities of the apical GPI-anchored protein DAF to open the tight junction
      barrier, gain access to the primary receptor CAR, and activate virus
      internalization by a caveolin-dependent pathway.

PMID- 16459292
TI  - Planar cell polarity planes the inconveniences of cell division into a smooth
      morphogenetic process.
AB  - Cell divisions are necessary, but also very disruptive for morphogenesis.
      Dividing cells lose many intercellular contacts and polarized features. This
      breaks the magnificent topology of the developing embryo and, if left unrepaired,
      can lead to severe tissue disorganization. A recent study demonstrated that cells
      use the planar cell polarity pathway to reestablish polarity and reintegrate
      daughter cells into developing tissue.

PMID- 16459293
TI  - Tolloid gets Sizzled competing with Chordin.
AB  - The enigma of Sizzled, a secreted Frizzled-related protein, has been resolved in
      a recent study from the De Robertis lab ( [in the January 13 issue of Cell]).
      Sizzled, although homologous to other Wnt antagonists, does not function as such,
      nor does it function within a Wnt signaling pathway. Remarkably it functions as
      an antagonist of BMP signaling, competing with Chordin for binding to its
      inhibitor a Tolloid-related metalloprotease. This competition protects Chordin
      from cleavage, thus allowing it to bind and limit BMP signaling.

PMID- 16459294
TI  - Mammalian variations on a theme: a Smo and Sufu surprise.
AB  - Hedgehog signaling plays a critical role during development and tumorigenesis.
      While much mechanistic insight has come from pathway investigations in the fruit
      fly, recent studies suggest a distinct mammalian strategy for signaling from
      Smoothened to Gli through the novel protein Suppressor of Fused that may have
      therapeutic implications.

PMID- 16459295
TI  - A role for neurotrophins in embryonic stem cell growth.
AB  - Neurotrophins act on embryonic cells through TRK receptors to inhibit apoptosis
      by phosphorylation of AKT. In a recent paper in Nature Biotechnology, show that
      the presence of selected neurotrophins enables cloning of trypsinized single
      embryonic stem cells and potentially increases the availability and usefulness of
      these stem cells.

PMID- 16459296
TI  - Palmitoylation of the EGFR ligand Spitz by Rasp increases Spitz activity by
      restricting its diffusion.
AB  - Lipid modifications such as palmitoylation or myristoylation target intracellular
      proteins to cell membranes. Secreted ligands of the Hedgehog and Wnt families are
      also palmitoylated; this modification, which requires the related transmembrane
      acyltransferases Rasp and Porcupine, can enhance their secretion, transport, or
      activity. We show here that rasp is also essential for the developmental
      functions of Spitz, a ligand for the Drosophila epidermal growth factor receptor
      (EGFR). In cultured cells, Rasp promotes palmitate addition to the N-terminal
      cysteine residue of Spitz, and this cysteine is required for Spitz activity in
      vivo. Palmitoylation reduces Spitz secretion and enhances its plasma membrane
      association, but does not alter its ability to activate the EGFR in vitro. In
      vivo, overexpressed unpalmitoylated Spitz has an increased range of action but
      reduced activity. These data suggest a role for palmitoylation in restricting
      Spitz diffusion, allowing its local concentration to reach the threshold required
      for biological function.

PMID- 16459297
TI  - Divergence of hedgehog signal transduction mechanism between Drosophila and
      mammals.
AB  - The Hedgehog (Hh) signaling pathway has conserved roles in development of species
      ranging from Drosophila to humans. Responses to Hh are mediated by the
      transcription factor Cubitus interruptus (Ci; GLIs 1-3 in mammals), and
      constitutive activation of Hh target gene expression has been linked to several
      types of human cancer. In Drosophila, the kinesin-like protein Costal2 (Cos2),
      which associates directly with the Hh receptor component Smoothened (Smo), is
      essential for suppression of the transcriptional activity of Ci in the absence of
      ligand. Another protein, Suppressor of Fused (Su(Fu)), exerts a weak negative
      influence on Ci activity. Based on analysis of functional and sequence
      conservation of Cos2 orthologs, Su(Fu), Smo, and Ci/GLI proteins, we find here
      that Drosophila and mammalian Hh signaling mechanisms have diverged, and that, in
      mouse cells, major Cos2-like activities are absent and the inhibition of the Hh
      pathway in the absence of ligand critically depends on Su(Fu).

PMID- 16459298
TI  - Genetic elimination of Suppressor of fused reveals an essential repressor
      function in the mammalian Hedgehog signaling pathway.
AB  - The Hedgehog (Hh) pathway plays important roles during embryogenesis and
      carcinogenesis. Here, we show that ablation of the mouse Suppressor of fused
      (Sufu), an intracellular pathway component, leads to embryonic lethality at
      approximately E9.5 with cephalic and neural tube defects. Fibroblasts derived
      from Sufu(-/-) embryos showed high Gli-mediated Hh pathway activity that could
      not be modulated at the level of Smoothened and could only partially be blocked
      by PKA activation. Despite the robust constitutive pathway activation in the
      Sufu(-/-) fibroblasts, the GLI1 steady-state localization remained largely
      cytoplasmic, implying the presence of an effective nuclear export mechanism.
      Sufu(+/-) mice develop a skin phenotype with basaloid changes and jaw
      keratocysts, characteristic features of Gorlin syndrome, a human genetic disease
      linked to enhanced Hh signaling. Our data demonstrate that, in striking contrast
      to Drosophila, in mammals, Sufu has a central role, and its loss of function
      leads to potent ligand-independent activation of the Hh pathway.

PMID- 16459299
TI  - Stabilization of cell polarity by the C. elegans RING protein PAR-2.
AB  - Asymmetric localization of PAR proteins is a hallmark of polarized cells, but the
      mechanisms that create PAR asymmetry are not well understood. In the C. elegans
      zygote, PAR asymmetry is initiated by a transient actomyosin contraction, which
      sweeps the PAR-3/PAR-6/PKC-3 complex toward the anterior pole of the egg. The
      RING finger protein PAR-2 accumulates in a complementary pattern in the posterior
      cortex. Here we present evidence that PAR-2 participates in a feedback loop to
      stabilize polarity. PAR-2 is a target of the PKC-3 kinase and is excluded from
      the anterior cortex by PKC-3-dependent phosphorylation. The RING domain of PAR-2
      is required to overcome inhibition by PKC-3 and stabilize PAR-2 on the posterior
      cortex. Cortical PAR-2 in turn prevents PAR-3/PAR-6/PKC-3 from returning to the
      posterior, in a PAR-1- and PAR-5-dependent manner. Our findings suggest that
      reciprocal inhibitory interactions among PAR proteins stabilize polarity by
      reinforcing an initial asymmetry in PKC-3.

PMID- 16459300
TI  - Polarized transport of Frizzled along the planar microtubule arrays in Drosophila
      wing epithelium.
AB  - Cells in a variety of developmental contexts sense extracellular cues that are
      given locally on their surfaces, and subsequently amplify the initial signal to
      achieve cell polarization. Drosophila wing cells acquire planar polarity along
      the proximal-distal (P-D) axis, in which the amplification of the presumptive cue
      involves assembly of a multiprotein complex that spans distal and proximal
      boundaries of adjacent cells. Here we pursue the mechanisms that place one of the
      components, Frizzled (Fz), at the distal side. Intracellular particles of GFP
      tagged Fz moved preferentially toward distal boundaries before Fz::GFP and other
      components were tightly localized at the P/D cortex. Arrays of microtubules (MTs)
      were approximately oriented along the P-D axis and these MTs contributed to the
      formation of the cortical complex. Furthermore, there appeared to be a bias in
      the P-D MTs, with slightly more plus ends oriented distally. The hypothesis of
      polarized vesicular trafficking of Fz is discussed.

PMID- 16459301
TI  - The physiological function of von Willebrand's factor depends on its tubular
      storage in endothelial Weibel-Palade bodies.
AB  - Weibel-Palade bodies are the 1-5 microm long rod-shaped storage organelles of
      endothelial cells. We have investigated the determinants and functional
      significance of this shape. We find that the folding of the hemostatic protein
      von Willebrand's factor (VWF) into tubules underpins the rod-like shape of Weibel
      Palade bodies. Further, while the propeptide and the N-terminal domains of mature
      VWF are sufficient to form tubules, their maintenance relies on a pH-dependent
      interaction between the two. We show that the tubular conformation of VWF is
      essential for a rapid unfurling of 100 microm long, platelet-catching VWF
      filaments when exposed to neutral pH after exocytosis in cell culture and in
      living blood vessels. If tubules are disassembled prior to exocytosis, then short
      or tangled filaments are released and platelet recruitment is reduced. Thus, a
      100-fold compaction of VWF into tubules determines the unique shape of Weibel
      Palade bodies and is critical to this protein's hemostatic function.

PMID- 16459302
TI  - Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin
      internalization and recycling.
AB  - Clathrin-mediated endocytosis is involved in the internalization, recycling, and
      degradation of cycling membrane receptors as well as in the biogenesis of
      synaptic vesicle proteins. While many constitutively internalized cargo proteins
      are recognized directly by the clathrin adaptor complex AP-2, stimulation
      dependent endocytosis of membrane proteins is often facilitated by specialized
      sorting adaptors. Although clathrin-mediated endocytosis appears to be a major
      pathway for presynaptic vesicle cycling, no sorting adaptor dedicated to synaptic
      vesicle membrane protein endocytosis has been indentified in mammals. Here, we
      show that stonin 2, a mammalian ortholog of Drosophila stoned B, facilitates
      clathrin/AP-2-dependent internalization of synaptotagmin and targets it to a
      recycling vesicle pool in living neurons. The ability of stonin 2 to facilitate
      endocytosis of synaptotagmin is dependent on its association with AP-2, an intact
      mu-homology domain, and functional AP-2 heterotetramers. Our data identify stonin
      2 as an AP-2-dependent endocytic sorting adaptor for synaptotagmin
      internalization and recycling.

PMID- 16459303
TI  - Bearded family members inhibit Neuralized-mediated endocytosis and signaling
      activity of Delta in Drosophila.
AB  - Endocytosis of Notch receptor ligands in signaling cells is essential for Notch
      receptor activation. In Drosophila, the E3 ubiquitin ligase Neuralized (Neur)
      promotes the endocytosis and signaling activity of the ligand Delta (Dl). In this
      study, we identify proteins of the Bearded (Brd) family as interactors of Neur.
      We show that Tom, a prototypic Brd family member, inhibits Neur-dependent Notch
      signaling. Overexpression of Tom inhibits the endocytosis of Dl and interferes
      with the interaction of Dl with Neur. Deletion of the Brd gene complex results in
      ectopic endocytosis of Dl in dorsal cells of stage 5 embryos. This defect in Dl
      trafficking is associated with ectopic expression of the single-minded gene, a
      direct Notch target gene that specifies the mesectoderm. We propose that
      inhibition of Neur by Brd proteins is important for precise spatial regulation of
      Dl signaling.

PMID- 16459304
TI  - Dorsal-ventral pattern of Delta trafficking is established by a Snail-Tom
      Neuralized pathway.
AB  - The intracellular trafficking of the Notch ligand Delta plays an important role
      in the activation of the Notch pathway. We have addressed the snail-dependent
      regulation of Delta trafficking during the plasma membrane growth of the mesoderm
      in the Drosophila embryo. We show that Delta is retained in endocytic vesicles in
      the mesoderm but expressed on the surface of the adjacent ectoderm. This
      trafficking pattern requires Neuralized. We developed a protocol based on
      chromosomal deletion and microarray analysis that led to the identification of
      tom as the target of snail regulating Delta trafficking. Snail represses Tom
      expression in the mesoderm and thereby activates Delta trafficking.
      Overexpression of Tom abolishes Delta trafficking and signaling to the adjacent
      mesoectoderm. Loss of Tom produces mesoderm-type Delta trafficking in the entire
      blastoderm epithelium and an expansion of mesoectoderm gene expression. We
      propose that Tom antagonizes the activity of Neuralized and thus establishes a
      sharp mesoderm-mesoectoderm boundary of Notch signaling.

PMID- 16459305
TI  - Auxin triggers transient local signaling for cell specification in Arabidopsis
      embryogenesis.
AB  - The Arabidopsis embryonic root meristem is initiated by the specification of a
      single cell, the hypophysis. This event critically requires the antagonistic
      auxin response regulators MONOPTEROS and BODENLOS, but their mechanism of action
      is unknown. We show that these proteins interact and transiently act in a small
      subdomain of the proembryo adjacent to the future hypophysis. Here they promote
      transport of auxin, which then elicits a second response in the hypophysis
      itself. Our results suggest that hypophysis specification is not the direct
      result of a primary auxin response but rather depends on cell-to-cell signaling
      triggered by auxin in adjacent cells.

PMID- 16459306
TI  - Certainly can't live without this: SIRT6.
AB  - Cellular metabolic rates might regulate aging by impinging on genomic stability
      through the DNA repair pathways. A new study published in Cell (Mostoslavsky et
      al., 2006) reports that deficiency in one of the mammalian Sir2 homologs, SIRT6,
      results in genome instability through the DNA base excision repair pathway and
      leads to aging-associated degenerative phenotypes.

PMID- 16459307
TI  - The molecular genetics of the melanocortin pathway and energy homeostasis.
AB  - The CNS melanocortin pathway plays an important role in the control of body
      weight. Two papers in this issue of Cell Metabolism, Lee et al., 2006 and
      Biebermann et al., 2006, suggest that beta MSH--a product of POMC processing-
      plays an unanticipated role in this pathway in humans.

PMID- 16459308
TI  - Unlikely partners in weight loss?
AB  - The classic role of bile acids is as a key component of cholesterol homeostasis.
      New evidence recently published in Nature (Watanabe et al., 2006), however,
      describes a bile acid signaling pathway that controls energy expenditure through
      induction of thyroid hormone signaling pathways. This work may point to new
      approaches to tissue-specific metabolic regulation.

PMID- 16459309
TI  - AgRP in energy balance: Will the real AgRP please stand up?
AB  - The neuropeptide AgRP promotes food intake and weight gain by antagonizing
      signaling at melanocortin 3 and 4 receptors in the brain, but the limited
      phenotype of mice lacking AgRP raised questions about its importance. Four recent
      studies addressed this by creating mice in which AgRP neurons, which also express
      NPY and GABA, are ablated postnatally, and although details vary, they suggest
      that AgRP neurons are more essential to feeding and weight gain than is AgRP
      itself. A recent paper in Cell Metabolism (Wortley et al., 2005) indicates that
      AgRP itself is important for feeding and weight gain, but only as mice age, and
      the mechanism may involve dysfunction of the thyroid axis.

PMID- 16459310
TI  - miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting.
AB  - Current understanding of microRNA (miRNA) biology is limited, and antisense
      oligonucleotide (ASO) inhibition of miRNAs is a powerful technique for their
      functionalization. To uncover the role of the liver-specific miR-122 in the adult
      liver, we inhibited it in mice with a 2'-O-methoxyethyl phosphorothioate ASO. miR
      122 inhibition in normal mice resulted in reduced plasma cholesterol levels,
      increased hepatic fatty-acid oxidation, and a decrease in hepatic fatty-acid and
      cholesterol synthesis rates. Activation of the central metabolic sensor AMPK was
      also increased. miR-122 inhibition in a diet-induced obesity mouse model resulted
      in decreased plasma cholesterol levels and a significant improvement in liver
      steatosis, accompanied by reductions in several lipogenic genes. These results
      implicate miR-122 as a key regulator of cholesterol and fatty-acid metabolism in
      the adult liver and suggest that miR-122 may be an attractive therapeutic target
      for metabolic disease.

PMID- 16459311
TI  - Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and
      triglyceride/VLDL secretion.
AB  - Forkhead transcription factor Foxa2 activates genes involved in hepatic lipid
      metabolism and is regulated by insulin. Activation of Foxa2 in the liver leads to
      increased oxidation and secretion of fatty acids in the form of triacylglycerols
      (TAGs), a process impaired in type 2 diabetes. Here, we demonstrate that Foxa2 is
      coactivated by PPARgamma coactivator beta (Pgc-1beta). Adenoviral expression of
      Foxa2 and Pgc-1beta in livers of ob/ob mice results in decreased hepatic TAG
      content and increased plasma TAG concentrations. In addition, the concerted
      action of Foxa2/Pgc-1beta activates genes in mitochondrial beta oxidation and
      enhances fatty acid metabolism. Furthermore, Foxa2/Pgc-1beta induce the
      expression of microsomal transfer protein, thereby increasing apoB-containing
      VLDL secretion. This process is inhibited by insulin through a Foxa2-dependent
      mechanism. These data demonstrate that Foxa2/Pgc-1beta regulate hepatic lipid
      homeostasis by affecting the clearance rate of fatty acids through oxidation
      and/or secretion of lipids in response to insulin.

PMID- 16459312
TI  - Critical roles of the p160 transcriptional coactivators p/CIP and SRC-1 in energy
      balance.
AB  - Several transcriptional coactivators have been implicated in modulating the
      transcriptional activities of nuclear hormone receptors in vitro. Potential roles
      of these cofactors in important physiological processes such as energy
      homeostasis remain unknown. We report here that a developmental arrest in
      interscapular brown fat and defective adaptive thermogenesis occur in mice
      lacking both the p160 family transcriptional coactivators SRC-1 and p/CIP due to
      a failure in induction of selective PPARgamma target genes involved in
      adipogenesis and mitochondrial uncoupling. In the absence of p/CIP and SRC-1,
      mice eat more food on both regular chow and a high-fat diet because of decreased
      blood leptin levels. However, the p/CIP(-/-)/SRC-1(-/-) mice are lean and
      resistant to high-fat-diet-induced obesity. They exhibit increased basal
      metabolic rates and heightened levels of physical activity. Therefore, p/CIP and
      SRC-1 play critical roles in energy balance by controlling both energy intake and
      energy expenditure.

PMID- 16459313
TI  - cAMP-dependent phosphorylation of PTB1 promotes the expression of insulin
      secretory granule proteins in beta cells.
AB  - Glucose stimulates the exocytosis of insulin secretory granules of pancreatic
      beta cells. Granule stores are quickly refilled by activation of
      posttranscriptional mechanisms that enhance the biosynthesis of granule
      components. Rapid replacement of granules is important to sustain insulin
      secretion, since new granules appear to be preferentially released.
      Posttranscriptional regulation of granule biogenesis includes the glucose-induced
      nucleocytoplasmic translocation of polypyrimidine tract binding protein 1 (PTB1),
      which binds mRNAs encoding granule proteins, and thus promotes their
      stabilization and translation. Glucagon-like peptide 1 (GLP-1) potentiates
      glucose-stimulated insulin gene expression and secretion by increasing cAMP
      levels in beta cells. Here, we show that elevation of cAMP levels causes the
      protein kinase A-dependent phosphorylation and nucleocytoplasmic translocation of
      PTB1, thereby preventing the rapid degradation of insulin mRNA and enhancing the
      expression of various granule proteins. Taken together, these findings identify
      PTB1 as a common downstream target of glucose and GLP-1 for the
      posttranscriptional upregulation of granule biogenesis.

PMID- 16459314
TI  - A POMC variant implicates beta-melanocyte-stimulating hormone in the control of
      human energy balance.
AB  - The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy
      balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, alpha- and beta
      MSH, the majority of attention has focused on alpha-MSH, partly reflecting the
      absence of beta-MSH in rodents. We screened the POMC gene in 538 patients with
      severe, early-onset obesity and identified five unrelated probands who were
      heterozygous for a rare missense variant in the region encoding beta-MSH,
      Tyr221Cys. This frequency was significantly increased (p < 0.001) compared to the
      general UK Caucasian population and the variant cosegregated with
      obesity/overweight in affected family members. Compared to wild-type beta-MSH,
      the variant peptide was impaired in its ability to bind to and activate signaling
      from the MC4R. Obese children carrying the Tyr221Cys variant were hyperphagic and
      showed increased linear growth, both of which are features of MC4R deficiency.
      These studies support a role for beta-MSH in the control of human energy
      homeostasis.

PMID- 16459315
TI  - A role for beta-melanocyte-stimulating hormone in human body-weight regulation.
AB  - Pro-opiomelanocortin (POMC) expressing neurons mediate the regulation of
      orexigenic drive by peripheral hormones such as leptin, cholecystokinin, ghrelin,
      and insulin. Most research effort has focused on alpha-melanocyte-stimulating
      hormone (alpha-MSH) as the predominant POMC-derived neuropeptide in the central
      regulation of human energy balance and body weight. Here we report a missense
      mutation within the coding region of the POMC-derived peptide beta-MSH (Y5C-beta
      MSH) and its association with early-onset human obesity. In vitro and in vivo
      data as well as postmortem human brain studies indicate that the POMC-derived
      neuropeptide beta-MSH plays a critical role in the hypothalamic control of body
      weight in humans.

PMID- 16459317
TI  - Research in physical and rehabilitation medicine in Europe: how are we doing?

PMID- 16459320
TI  - Role of heme oxygenase in the protection afforded skeletal muscle during ischemic
      tolerance.
AB  - OBJECTIVE: Ischemic tolerance (IT) is known to improve resistance to
      ischemia/reperfusion (I/R)-induced injury; however, the mechanisms remain
      unknown. The authors hypothesized that induction of heme oxygenase (HO), a heat
      shock protein, would provide anti-inflammatory benefits during IT, thereby
      preventing leukocyte-derived I/R injury. METHODS: Male Wistar rats were randomly
      assigned to sham (n = 4), I/R (n = 9), preconditioning (PC)+I/R (n = 7), chromium
      mesoporphyrin, to inhibit HO (CrMP; n = 4), or PC+I/R+CrMP (n = 6) groups. PC
      consisted of 5 cycles of I/R, each lasting 10 min, induced by tightening a
      tourniquet placed above the greater trochantor of the hindlimb. Twenty-four hours
      later, the hindlimb underwent 2 h of no-flow ischemia followed by intravital
      microscopy during 90 min reperfusion to assess capillary perfusion (#/mm), tissue
      injury (ratio of ethidium bromide to bisbenzimide labeled cells/100 microm2),
      leukocyte rolling (Lr, #/1000 microm2), and adhesion (La, #/1000 microm2) in
      postcapillary venules of the extensor digitorum longus (EDL) muscle. RESULTS: In
      the I/R group, Lr was significantly increased (7.1 +/- 0.4) compared to sham (3.1
      +/- 0.4). PC+I/R increased Lr (10.8 +/- 0.72), which was further exacerbated by
      the removal of HO (14.2 +/- 1.3). La (7.8 +/- 2.0) was significantly increased
      compared to sham (2.4 +/- 0.9), while PC returned La back to sham levels (1.9 +/-
      0.7). Removal of HO activity, via CrMP, had no significant effect on La (3.9 +/-
      0.7). However, CrMP removed the protection to microvascular perfusion (I/R = 9.4
      +/- 1.1, PC = 16.6 +/- 1.8, sham = 20.5 +/- 2.8, PC+CrMP+I/R = 12.3 +/- 2.3) and
      prevented protection from ischemia-induced tissue injury. CONCLUSION: The data
      suggest that HO is an important protective mechanism during IT in skeletal
      muscle, but such protection was by mechanisms other than altered leukocyte
      endothelial cell interaction.

PMID- 16459321
TI  - Role of vascular heme oxygenase in reduced myogenic reactivity following chronic
      hypoxia.
AB  - OBJECTIVE: Exposure to chronic hypoxia (CH) results in a persistent endothelium
      dependent vascular smooth muscle hyperpolarization that diminishes
      vasoconstrictor reactivity. Experiments were performed to test the hypothesis
      that products of both cytochrome P450 epoxygenase (CYP) and heme oxygenase (HO)
      are required for the persistent diminished myogenic reactivity following CH.
      METHODS: The authors examined myogenic responses of mesenteric arteries isolated
      from control and CH (48 h; P(B) = 380 mmHg) rats in the presence of a HO
      inhibitor (zinc protoporphyrin IX; ZnPPIX) or combined HO and CYP epoxygenase
      inhibition (sulfaphenazole). Arteries were isolated and cannulated and the
      vascular smooth muscle was loaded with the Ca2+ indicator Fura-2. RESULTS:
      Control vessels maintained their internal diameter in response to step increases
      in intraluminal pressure, whereas arteries from CH animals passively distended.
      ZnPPIX augmented myogenic reactivity and [Ca2+] in arteries from CH animals.
      Combined administration of sulfaphenazole and ZnPPIX did not have an additional
      effect compared to ZnPPIX alone. Myogenic reactivity in control vessels was not
      altered by ZnPPIX or ZnPPIX + sulfaphenazole. CONCLUSIONS: HO appears to play a
      role in regulating myogenic reactivity following CH. Furthermore, these data
      suggest that products of HO and CYP are both required for the observed
      attenuation in vasoreactivity following CH.

PMID- 16459322
TI  - Platelet recruitment in the murine hepatic microvasculature during experimental
      sepsis: role of neutrophils.
AB  - OBJECTIVES: Sepsis is a major clinical problem that often results in the
      dysfunction or failure of multiple organs, including the liver. While
      inflammatory cell activation has been implicated as an early critical event in
      sepsis-induced liver dysfunction, there is growing evidence for the involvement
      of activated platelets in this pathologic process. METHODS: Intravital microscopy
      was used in this study to assess the magnitude and time course of platelet
      adhesion in the liver microcirculation during experimental sepsis and to
      determine whether the platelet accumulation is linked to leukocyte infiltration.
      The adhesion of platelets and leukocytes in terminal hepatic venules (THV) and
      sinusoids was quantified at 2, 4, and 6 h after abdominal sepsis induced by cecal
      ligation and puncture (CLP). RESULTS: While the rolling and firm adhesion of
      platelets and leukocytes in THV were not altered in the first 2 h after CLP,
      platelet recruitment was observed at 4 h and further elevated at 6 h after CLP.
      Leukocyte adhesion in THV exhibited a similar time course. A similar accumulation
      of blood cells in sinusoids was noted after CLP. This was accompanied by an
      increased number of nonperfused sinusoids. CLP-induced leukocyte and platelet
      recruitment in THV and sinusoids was attenuated in mice rendered neutropenic with
      anti-neutrophil serum. CONCLUSION: These findings indicate that sepsis is
      associated with a neutrophil-dependent recruitment of platelets in the liver
      microcirculation that impairs sinusoidal perfusion and may contribute to the
      liver dysfunction associated with sepsis.

PMID- 16459323
TI  - Induction of LFA-1-dependent neutrophil rolling on ICAM-1 by engagement of E
      selectin.
AB  - OBJECTIVE: To study rolling of mouse neutrophils on E-selectin and ICAM-1 in an
      ex vivo flow chamber system. METHODS: The authors developed a small autoperfused
      flow chamber (20 x 200-microm cross section) that allows direct visualization of
      cells with and without fluorescent labeling and does not require recirculation of
      blood. RESULTS: Neutrophils rolled on E-selectin alone, but were unable to
      interact with immobilized ICAM-1. When ICAM-1 was co-immobilized with E-selectin,
      the number of cells that rolled was doubled, but no significant firm adhesion was
      observed. This phenomenon was specific for E-selectin, and no enhancement of
      rolling was observed when P-selectin was immobilized with ICAM-1. The increased
      neutrophil rolling seen on E-selectin and ICAM-1 substrates required beta2
      integrins. Treating mice with antibodies to the beta2 integrins LFA-1 and Mac-1
      showed that LFA-1 was primarily responsible for mediating rolling on ICAM-1 in
      this model. Increased rolling on E-selectin and ICAM-1 was significantly reduced
      following administration of a specific p38 mitogen-activated protein kinase
      (MAPK) inhibitor. CONCLUSION: The data show that neutrophil rolling on E-selectin
      leads to partial activation of LFA-1, enabling LFA-1-dependent rolling on ICAM-1.
      This mechanism is likely to amplify and accelerate neutrophil recruitment in
      inflammation.

PMID- 16459324
TI  - A practical extension of hydrodynamic theory of porous transport for hydrophilic
      solutes.
AB  - OBJECTIVE: The equations for transport of hydrophilic solutes through aqueous
      pores provide a fundamental basis for examining capillary-tissue exchange and
      water and solute flux through transmembrane channels, but the theory remains
      incomplete for ratios, alpha, of sphere diameters to pore diameters greater than
      0.4. Values for permeabilities, P, and reflection coefficients, sigma, from
      Lewellen, working with Lightfoot et al., at alpha = 0.5 and 0.95, were combined
      with earlier values for alpha < 0.4, and the physically required values at alpha
      = 1.0, to provide accurate expressions over the whole range of 0 < alpha < 1.
      METHODS: The "data" were the long-accepted theory for alpha < 0.2 and the
      computational results from Lewellen and Lightfoot et al. on hard spheres (of 5
      different alpha's) moving by convection and diffusion through a tight cylindrical
      pore, accounting for molecular exclusion, viscous forces, pressure drop, torque
      and rotation of spheres off the center line (averaging across all accessible
      radial positions), and the asymptotic values at alpha = 1.0. Coefficients for
      frictional hindrance to diffusion, F(alpha), and drag, G(alpha), and functions
      for sigma(alpha) and P(alpha), were represented by power law functions and the
      parameters optimized to give best fits to the combined "data." RESULTS: The
      reflection coefficient sigma = {1 - [1 - (1 - phi)2]G'(alpha)} + 2alpha2 phi
      F'(alpha), and the relative permeability P/Pmax = phi F '(alpha)[1 + 9alpha5.5 x
      (1.0 - alpha5)0.02], where phi is the partition coefficient or volume fraction of
      the pore available to solute. The new expression for the diffusive hindrance is
      F'(alpha) = (1 - alpha2)(3/2) phi/[1 + 0.2 x alpha2 x (1 - alpha2)16], and for
      the drag factor is G'(alpha) = (1 - 2alpha(2)/3 - 0.20217 alpha5)/(1 - 0.75851
      alpha5) - 0.0431[1 - (1 - alpha10)]. All of these converge monotonically to the
      correct limits at alpha = 1. CONCLUSIONS: These are the first expressions
      providing hydrodynamically based estimates of sigma(alpha) and P(alpha) over 0 <
      alpha < 1 They should be accurate to within 1-2%.

PMID- 16459325
TI  - A role for heterocellular coupling and EETs in dilation of rat cremaster
      arteries.
AB  - OBJECTIVE: The authors probed endothelium-dependent dilation and endothelial cell
      Ca2+ handling in myogenically active resistance arteries. METHODS: First-order
      arteries were removed from rat cremaster muscles, cannulated, and pressurized (75
      mmHg). Vessel diameter and endothelial cell Ca2+ were monitored using confocal
      microscopy, and arterial ultrastructure was determined using electron microscopy.
      RESULTS: Acetylcholine (ACh) stimulated elevations and oscillations in
      endothelial cell Ca2+, and concentration-dependently dilated arteries with
      myogenic tone. NO-independent dilation was blocked by 35 mM K+. Combined IK(Ca)
      (1 microM TRAM-34) and SK(Ca) (100 nM apamin) blockade partially inhibited NO
      independent relaxations, with residual relaxations sensitive to BK(Ca) or
      cytochrome P-450 inhibition (100 nM iberiotoxin, and 20 microM 17-ODYA or 10
      microM MS-PPOH). 11,12-EET stimulated iberiotoxin-sensitive dilation, but did not
      affect endothelial cell Ca2+. 15 mM K+ evoked dilation sensitive to inhibition of
      K(IR) (30 microM Ba2+) and Na+/K+-ATPase (10 microM ouabain), whereas these
      blockers did not affect ACh-mediated dilations. Homo- and heterocellular gap
      junctions were identified in radial sections through arteries. CONCLUSION: These
      data suggest that rises in endothelial cell Ca2+ stimulate SK(Ca) and IK(Ca)
      channels, leading to hyperpolarization and dilation, likely due to electrical
      coupling. In addition, a component was unmasked following SK(Ca) and IK(Ca)
      blockade, attributable to activation of BK(Ca) channels by cytochrome P-450
      metabolites.

PMID- 16459329
TI  - Functional domains and dynamic assembly of the peroxin Pex14p, the entry site of
      matrix proteins.
AB  - The 41-kDa membrane-anchored peroxin Pex14p functions as the peroxisome targeting
      signal (PTS) receptor-mediated, initial import site for matrix proteins. We here
      identify the functional domains of Pex14p involved in the assembly of import site
      subcomplexes. The minimal region of Pex14p required for restoring impaired
      protein import in pex14 Chinese hamster ovary cell mutant lies at residues 21-260
      in the primary sequence. A highly conserved N-terminal region, encompassing
      residues 21-70, interacts with the PTS1 receptor Pex5p, Pex13p, and Pex19p that
      is essential for membrane biogenesis. N-terminal residues 21-140, including a
      hydrophobic segment at 110-138, function as a topogenic sequence. Site-directed
      mutagenesis, size fractionation, and chemical cross-linking analyses demonstrate
      that the coiled-coil domain at residues 156-197 regulates homodimerization of
      Pex14p. Moreover, AXXXA and GXXXG motifs in the transmembrane segment mediate
      homomeric oligomerization of Pex14p, giving rise to assembly of high molecular
      mass complexes and thereby assuring Pex13p-dependent localization of Pex14p to
      peroxisomes. Pex5p, Pex13p, and Pex19p bind to Pex14p homo-oligomers with
      different molecular masses, whereas cargo-unloaded Pex5p apparently disassembles
      Pex14p homo-oligomers. Thus, Pex14p most likely forms several distinct peroxin
      complexes involved in peroxisomal matrix protein import.

PMID- 16459330
TI  - Oncostatin M receptor-mediated signal transduction is negatively regulated by
      SOCS3 through a receptor tyrosine-independent mechanism.
AB  - Down-regulation of interleukin (IL)-6-type cytokine signaling has been shown to
      occur, among other mechanisms, via induction of the feedback inhibitor SOCS3
      (suppressor of cytokine signaling 3). Binding of SOCS3 to the phosphorylated
      Tyr(759) in the cytoplasmic region of gp130, the common signal transducing
      receptor chain of all IL-6-type cytokines, is necessary for inhibition of Janus
      kinase-mediated signaling. In the present study, we analyzed the effect of SOCS3
      on signal transduction by the proinflammatory cytokine oncostatin M (OSM), which
      signals through a receptor complex of gp130 and the OSM receptor (OSMR). OSM
      leads to a much stronger and prolonged induction of SOCS3 in HepG2 hepatoma cells
      and murine embryonal fibroblasts (MEF) compared with IL-6. A negative effect of
      SOCS3 on OSM signaling was confirmed using MEF cells lacking SOCS3. We can show
      that the OSMR-mediated signaling is inhibited by SOCS3 to a similar extent as
      previously described for gp130. However, the inhibition occurs independent of
      tyrosine motifs within the OSMR. Instead, SOCS3 interacts directly with JAK1 in a
      stimulation-dependent manner, a mechanism so far only known for SOCS1.

PMID- 16459331
TI  - Regulation of ornithine decarboxylase.
AB  - Ornithine decarboxylase (ODC) initiates the polyamine biosynthetic pathway. The
      amount of ODC is altered in response to many growth factors, oncogenes, and tumor
      promoters and to changes in polyamine levels. Susceptibility to tumor development
      is increased in transgenic mice expressing high levels of ODC and is decreased in
      mice with reduced ODC due to loss of one ODC allele or elevated expression of
      antizyme, a protein that stimulates ODC degradation. This review describes key
      factors that contribute to the regulation of ODC levels, which can occur at the
      levels of transcription, translation, and protein turnover.

PMID- 16459333
TI  - The carotenase AtCCD1 from Arabidopsis thaliana is a dioxygenase.
AB  - Apocarotenoids resulting from the oxidative cleavage of carotenoids serve as
      important signaling and accessory molecules in a variety of biological processes.
      The enzymes catalyzing these reactions are referred to as carotenases or
      carotenoid oxygenases. Whether they act according to a monooxygenase mechanism,
      requiring two oxygens from different sources, or a dioxygenase mechanism is still
      a topic of controversy. In this study, we utilized the readily available beta-apo
      8'-carotenal as a substrate for the heterologously expressed AtCCD1 protein from
      Arabidopsis thaliana to investigate the oxidative cleavage mechanism of the 9,10
      double bond of carotenoids. Beta-ionone and a C(17)-dialdehyde were detected as
      products by gas and liquid chromatography-mass spectrometry as well as NMR
      analysis. Labeling experiments using H(2)(18)O or (18) O(2) showed that the
      oxygen in the keto-group of beta-ionone is derived solely from molecular
      dioxygen. When experiments were performed in an (18)O(2)-enriched atmosphere, a
      substantial fraction of the C(17)-dialdehyde contained labeled oxygen. The
      results unambiguously demonstrate a dioxygenase mechanism for the carotenase
      AtCCD1 from A. thaliana.

PMID- 16459332
TI  - The urokinase/PAI-2 complex: a new high affinity ligand for the endocytosis
      receptor low density lipoprotein receptor-related protein.
AB  - The efficient inactivation of urokinase plasminogen activator (uPA) by
      plasminogen activator inhibitor type 2 (PAI-2) at the surface of carcinoma cells
      is followed by rapid endocytosis of the uPA-PAI-2 complex. We now show that one
      pathway of this receptor-mediated endocytosis is mediated via the low density
      lipoprotein receptor-related protein (LRP) in prostate cancer cells. Detailed
      biochemical analyses using ligand binding assays and surface plasmon resonance
      revealed a novel and distinct interaction mechanism between native, human LRP and
      uPA-PAI-2. As reported previously for PAI-1, inhibition of uPA by PAI-2
      significantly increased the affinity of the complex for LRP (K(D) of 36 nm for
      uPA-PAI-2 versus 200 nm for uPA). This interaction was maintained in the presence
      of uPAR, confirming the validity of this interaction at the cell surface.
      However, unlike PAI-1, no interaction was observed between LRP and PAI-2 in
      either the stressed or the relaxed conformation. This suggests that the uPA-PAI-2
      LRP interaction is mediated by site(s) within the uPA molecule alone. Thus, as
      inhibition of uPA by PAI-2 resulted in accelerated clearance of uPA from the cell
      surface possibly via its increased affinity for LRP, this represents a mechanism
      through which PAI-2 can clear proteolytic activity from the cell surface.
      Furthermore, lack of a direct interaction between PAI-2 and LRP implies that
      downstream signaling events initiated by PAI-1 may not be activated by PAI-2.

PMID- 16459334
TI  - Transport of the IgE receptor alpha-chain is controlled by a multicomponent
      intracellular retention signal.
AB  - The human high affinity IgE receptor (FcepsilonRI) is a central component of the
      allergic response and is expressed as either a trimeric alphagamma2 or tetrameric
      alphabetagamma2 complex. It has been previously described that the cytoplasmic
      domain (CD) of the alpha-chain carries a dilysine motif at positions -3/-7 from
      the C terminus that functions in intracellular retention prior to assembly with
      other FcepsilonRI subunits. In this report we have further explored the role of
      the -3/-7 dilysine signal in controlling steady-state alpha-chain transport by
      mutational analysis and found little surface expression of a -3/-7 dialanine
      alpha-chain mutant but significant Golgi localization. We compared the transport
      properties of a series of alpha-chain cytoplasmic domain truncation mutants and
      observed that truncation mutants lacking 23 or more C-terminal residues showed a
      dramatic increase in steady-state transport suggesting a role for the membrane
      proximal CD sequence in alpha-chain retention. By performing alanine-scanning
      mutagenesis we identified a dilysine sequence (Lys(212)-Lys(216)) proximal to the
      transmembrane domain (TMD) that is important for both alpha-chain cell-surface
      expression and intracellular stability. Furthermore, co-mutation of the Lys(212)
      Lys(216) residues with the -3/-7 dilysine signal produced a dramatic increase in
      alpha-chain surface expression that was further increased by co-mutation of the
      lone charged residue (Asp(192)) in the TMD thereby defining three regions that
      function to regulate alpha-chain transport and in a highly synergistic manner.

PMID- 16459335
TI  - Mechanistic basis for the action of new cephalosporin antibiotics effective
      against methicillin- and vancomycin-resistant Staphylococcus aureus.
AB  - Emergence of methicillin-resistant Staphylococcus aureus (MRSA) has created
      challenges in treatment of nosocomial infections. The recent clinical emergence
      of vancomycin-resistant MRSA is a new disconcerting chapter in the evolution of
      these strains. S. aureus normally produces four PBPs, which are susceptible to
      modification by beta-lactam antibiotics, an event that leads to bacterial death.
      The gene product of mecA from MRSA is a penicillin-binding protein (PBP)
      designated PBP 2a. PBP 2a is refractory to the action of all commercially
      available beta-lactam antibiotics. Furthermore, PBP 2a is capable of taking over
      the functions of the other PBPs of S. aureus in the face of the challenge by beta
      lactam antibiotics. Three cephalosporins (compounds 1-3) have been studied
      herein, which show antibacterial activities against MRSA, including the
      clinically important vancomycin-resistant strains. These cephalosporins exhibit
      substantially smaller dissociation constants for the preacylation complex
      compared with the case of typical cephalosporins, but their pseudo-second-order
      rate constants for encounter with PBP 2a (k(2)/K(s)) are not very large (< or
      =200 m(-1) s(-1)). It is documented herein that these cephalosporins facilitate a
      conformational change in PBP 2a, a process that is enhanced in the presence of a
      synthetic surrogate for cell wall, resulting in increases in the k(2)/K(s)
      parameter and in more facile enzyme inhibition. These findings argue that the
      novel cephalosporins are able to co-opt interactions between PBP 2a and the cell
      wall in gaining access to the active site in the inhibition process, a set of
      events that leads to effective inhibition of PBP 2a and the attendant killing of
      the MRSA strains.

PMID- 16459336
TI  - Polyvinylpyrrolidone 40 assists the refolding of bovine carbonic anhydrase B by
      accelerating the refolding of the first molten globule intermediate.
AB  - Protecting proteins from aggregation is one of the most important issues in both
      protein science and protein engineering. In this research, the mechanism of
      enhancing the refolding of guanidine hydrochloride-denatured carbonic anhydrase B
      by polyvinylpyrrolidone 40 (PVP40) was studied by both kinetic and equilibrium
      refolding experiments. The reactivation and refolding kinetics indicated that the
      rate constant of refolding the first refolding intermediate (I(1)) to the second
      one (I(2)) is promoted by the addition of PVP. Fluorescence quenching studies
      further indicated that PVP could bind to the aggregation-prone species I(1),
      resulting in the protection of the exposed hydrophobic surface, a minimization of
      the protein surface, and more importantly, an increase of the refolding rate of
      I(1). These properties were quite different from those of poly(ethylene glycol)
      (PEG), which has been shown to have a strong and stoichiometric binding to I(1)
      and does not interfere with the refolding pathway. Unlike PEG, the binding of PVP
      to I(1) does not block the aggregation pathway directly but decreases the energy
      barrier for I(1) to refold to I(2) and thus reduces the accumulation of I(1).
      These results suggested that PVP works by a quite different mechanism from those
      well established ones in chaperones and chemical promoters. PVP is more like a
      folding catalyst rather than a chemical chaperone. The distinct mechanism of
      enhancing protein aggregation by PVP is expected to facilitate the attempt to
      develop new chemical compounds as well as new strategies to protect proteins from
      aggregation.

PMID- 16459337
TI  - Fulvestrant (ICI 182,780)-dependent interacting proteins mediate immobilization
      and degradation of estrogen receptor-alpha.
AB  - The antiestrogen fulvestrant (ICI 182,780) causes immobilization of estrogen
      receptor-alpha (ERalpha) in the nuclear matrix accompanied by rapid degradation
      by the ubiquitin-proteasome pathway. In this study we tested the hypothesis that
      fulvestrant induces specific nuclear matrix protein-ERalpha interactions that
      mediate receptor immobilization and turnover. A glutathione S-transferase (GST)
      ERalpha-activating function-2 (AF2) fusion protein was used to isolate and purify
      receptor-interacting proteins in cell lysates prepared from human MCF-7 breast
      cancer cells. After SDS-PAGE and gel excision, mass spectrometry was used to
      identify two major ERalpha-interacting proteins, cytokeratins 8 and 18
      (CK8.CK18). We determined, using ERalpha-activating function-2 mutants, that
      helix 12 (H12) of ERalpha, but not its F domain, is essential for fulvestrant
      induced ERalpha-CK8 and CK18 interactions. To investigate the in vivo role of H12
      in fulvestrant-induced ERalpha immobilization/degradation, transient transfection
      assays were performed using wild type ERalpha,ERalpha with a mutated H12, and
      ERalpha with a deleted F domain. Of those, only the ERalpha H12 mutant was
      resistant to fulvestrant-induced immobilization to the nuclear matrix and protein
      degradation. Fulvestrant treatment caused ERalpha degradation in CK8.CK18
      positive human breast cancer cells, and CK8 and CK18 depletion by small
      interference RNAs partially blocked fulvestrant-induced receptor degradation.
      Furthermore, fulvestrant-induced ERalpha degradation was not observed in CK8 or
      CK18-negative cancer cells, suggesting that these two intermediate filament
      proteins are necessary for fulvestrant-induced receptor turnover. Using an
      ERalpha-green fluorescent protein construct in fluorescence microscopy revealed
      that fulvestrant-induced cytoplasmic localization of newly synthesized receptor
      is mediated by its interaction with CK8 and CK18. In summary, this study provides
      the first direct evidence linking ERalpha immobilization and degradation to the
      nuclear matrix. We suggest that fulvestrant induces ERalpha to interact with CK8
      and CK18, drawing the receptor into close proximity to nuclear matrix-associated
      proteasomes that facilitate ERalpha turnover.

PMID- 16459338
TI  - Stabilization of the autoproteolysis of TNF-alpha converting enzyme (TACE)
      results in a novel crystal form suitable for structure-based drug design studies.
AB  - The crystallization of TNF-alpha converting enzyme (TACE) has been useful in
      understanding the structure-activity relationships of new chemical entities.
      However, the propensity of TACE to undergo autoproteolysis has made enzyme
      handling difficult and impeded the identification of inhibitor soakable crystal
      forms. The autoproteolysis of TACE was found to be specific (Y352-V353) and
      occurred within a flexible loop that is in close proximity to the P-side of the
      active site. The rate of autoproteolysis was found to be proportional to the
      concentration of TACE, suggesting a bimolecular reaction mechanism. A limited
      specificity study of the S(1)' subsite was conducted using surrogate peptides and
      suggested substitutions that would stabilize the proteolysis of the loop at
      positions Y352-V353. Two mutant proteases (V353G and V353S) were generated and
      proved to be highly resistant to autoproteolysis. The kinetics of the more
      resistant mutant (V353G) and wild-type TACE were compared and demonstrated
      virtually identical IC(50) values for a panel of competitive inhibitors. However,
      the k(cat)/K(m) of the mutant for a larger substrate (P6 - P(6)') was
      approximately 5-fold lower than that for the wild-type enzyme. Comparison of the
      complexed wild-type and mutant structures indicated a subtle shift in a
      peripheral P-side loop (comprising the mutation site) that may be involved in
      substrate binding/turnover and might explain the mild kinetic difference. The
      characterization of this stabilized form of TACE has yielded an enzyme with
      similar native kinetic properties and identified a novel crystal form that is
      suitable for inhibitor soaking and structure determination.

PMID- 16459339
TI  - Engineering of Escherichia coli L-serine O-acetyltransferase on the basis of
      crystal structure: desensitization to feedback inhibition by L-cysteine.
AB  - L-Serine O-acetyltransferase (SAT) from Escherichia coli catalyzes the first step
      of L-cysteine synthesis in E.coli and is strictly inhibited by the second step
      product, L-cysteine. To establish a fermentation process to produce L-cysteine,
      we embarked on a mutational study of E.coli SAT to desensitize the feedback
      inhibition by L-cysteine. The crystal structure and the reaction mechanism of SAT
      from E.coli have shown that the substrate L-serine and the inhibitor L-cysteine
      bind to the identical region in the SAT protein. To decrease the affinity for
      only L-cysteine, we first built the structure model of L-serine-binding SAT on
      the basis of the crystal structure with bound L-cysteine and compared these two
      structures. The comparison showed that the Calpha of Asp92 underwent a
      substantial positional change upon the replacement of L-cysteine by L-serine. We
      then introduced various amino acid substitutions at positions 89-96 around Asp92
      by randomized, fragment-directed mutagenesis to change the position of the Asp92.
      As a result, we successfully obtained mutant SATs which have both extreme
      insensitivity to an inhibition by L-cysteine (the concentration that inhibits 50%
      activity; IC(50) = 1,100 micromol/l, the inhibition constant; K(i) = 950.0
      micromol/l) and extremely high emzymatic activities.

PMID- 16459340
TI  - Acceptability of low molecular weight heparin thromboprophylaxis for inpatients
      receiving palliative care: qualitative study.
AB  - OBJECTIVE: To find out what inpatients with advanced cancer who are receiving
      palliative care think about the effect of thromoprophylaxis on overall quality of
      life. DESIGN: Qualitative study using audiotaping of semistructured interviews.
      SETTING: Regional cancer centre in Wales. PARTICIPANTS: 28 inpatients with
      advanced metastatic cancer receiving palliative care and low molecular weight
      heparin. MAIN OUTCOME MEASURES: Recurring themes on the effect of
      thromboprophylaxis on overall quality of life. RESULTS: Major emerging themes
      showed that patients knew about the risks of venous thromboembolism and the
      purpose of treatment with heparin. Media coverage had raised awareness about
      venous thromboembolism, and many had previous experience of thromboprophylaxis.
      All found low molecular weight heparin an acceptable intervention, and many said
      that it improved their quality of life by giving them a feeling of safety and
      reassurance. Antiembolic stockings were considered uncomfortable and had a
      negative impact on quality of life. Patients were concerned that because they had
      advanced disease they might not be eligible for thromboprophylaxis. CONCLUSION:
      Low molecular weight heparin is acceptable to inpatients with advanced cancer
      receiving palliative care and has a positive impact on overall quality of life.
      Antiembolic stockings are an unacceptable intervention in this patient group.
      Guidelines on thromboprophylaxis are urgently needed for palliative care
      inpatient units and hospices.

PMID- 16459342
TI  - Health-related social control and relationship interdependence among gay couples.
AB  - How gay partners influence each other to promote health and prevent human
      immunodeficiency virus (HIV) is poorly understood. The present study combined
      qualitative and quantitative methods to examine the experience of health-related
      social control and relationship processes among a sample of 60 gay male couples.
      Couples completed semistructured interviews and separate self-administered
      questionnaires. Findings suggest that partners attempt to change a variety of
      behaviors, many of which are not HIV related, that they use a variety of social
      control tactics, some of which are specific to HIV prevention, and that their
      care and concern for each other and their relationship motivate social control to
      change health behaviors. The implications for health behavior change research and
      intervention are discussed.

PMID- 16459341
TI  - Mutations of human TMHS cause recessively inherited non-syndromic hearing loss.
AB  - BACKGROUND: Approximately half the cases of prelingual hearing loss are caused by
      genetic factors. Identification of genes causing deafness is a crucial first step
      in understanding the normal function of these genes in the auditory system.
      Recently, a mutant allele of Tmhs was reported to be associated with deafness and
      circling behaviour in the hurry-scurry mouse. Tmhs encodes a predicted tetraspan
      protein of unknown function, which is expressed in inner ear hair cells. The
      human homologue of Tmhs is located on chromosome 6p. OBJECTIVE: To determine the
      cause of deafness in four consanguineous families segregating recessive deafness
      linked to markers on chromosome 6p21.1-p22.3 defining a novel DFNB locus.
      RESULTS: A novel locus for non-syndromic deafness DFNB67 was mapped in an
      interval of approximately 28.51 cM on human chromosome 6p21.1-p22.3. DNA sequence
      analysis of TMHS revealed a homozygous frameshift mutation (246delC) and a
      missense mutation (Y127C) in affected individuals of two families segregating non
      syndromic deafness, one of which showed significant evidence of linkage to
      markers in the DFNB67 interval. The localisation of mTMHS in developing mouse
      inner ear hair cells was refined and found to be expressed briefly from E16.5 to
      P3. CONCLUSIONS: These findings establish the importance of TMHS for normal sound
      transduction in humans.

PMID- 16459343
TI  - 'Raising the bar' for the treatment of pulmonary arterial hypertension.

PMID- 16459344
TI  - Antifungal agents for preventing fungal infections in non-neutropenic critically
      ill and surgical patients: systematic review and meta-analysis of randomized
      clinical trials.
AB  - OBJECTIVES: This study aims to systematically identify and summarize the effects
      of antifungal prophylaxis in non-neutropenic critically ill adult patients on all
      cause mortality and the incidence of invasive fungal infections. METHODS:
      Systematic review and meta-analysis of randomized controlled trials in all
      languages comparing the prophylactic use of any antifungal agent or regimen with
      placebo, no antifungal or another antifungal agent or regimen in non-neutropenic
      critically ill adult patients. We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2005), MEDLINE (1966
      to 2 September 2005) and EMBASE (1980 to week 36, 2005). We also hand-searched
      reference lists, abstracts of conference proceedings and scientific meetings
      (1998-2004) and contacted authors of included studies and pharmaceutical
      manufacturers. The primary outcomes assessed were all-cause mortality and proven
      invasive fungal infections. Two reviewers independently applied selection
      criteria, performed quality assessment and extracted data using an intention-to
      treat approach. Data were synthesized using the random effects model and
      expressed as relative risk with 95% confidence intervals. RESULTS: Twelve unique
      trials (eight comparing fluconazole and four ketoconazole with no antifungal or a
      non-absorbable agent) involving 1606 randomized patients were included. For both
      outcomes of total mortality and invasive fungal infections, almost all trials of
      fluconazole and ketoconazole separately showed a non-significant risk reduction
      with prophylaxis. When combined, fluconazole/ketoconazole reduced total mortality
      by one-quarter (relative risk 0.76, 95% confidence interval 0.59-0.97) and
      invasive fungal infections by about one-half (relative risk 0.46, 95% confidence
      interval 0.31-0.68). No significant increase in the incidence of infection or
      colonization with the azole-resistant fungal pathogens Candida glabrata or
      Candida krusei was demonstrated, although the confidence intervals of the summary
      effect measures were wide. Adverse effects requiring treatment discontinuation
      were not more common amongst patients receiving prophylaxis. Results across all
      trials were homogeneous despite considerable heterogeneity in clinical and
      methodological characteristics. CONCLUSIONS: Prophylaxis with fluconazole or
      ketoconazole in critically ill patients reduces invasive fungal infections by one
      half and total mortality by one-quarter. Although no significant increase in
      azole-resistant Candida species associated with prophylaxis was demonstrated,
      trials were not powered to exclude such an effect. In patients at increased risk
      of invasive fungal infections, antifungal prophylaxis with fluconazole should be
      considered.

PMID- 16459345
TI  - Daptomycin is more efficacious than vancomycin against a methicillin-susceptible
      Staphylococcus aureus in experimental meningitis.
AB  - OBJECTIVES: To test the efficacy of daptomycin, a cyclic lipopeptide antibiotic,
      against a methicillin-susceptible Staphylococcus aureus strain in experimental
      rabbit meningitis and to determine its penetration into non-inflamed and inflamed
      meninges RESULTS: Over a treatment period of 8 h, daptomycin (15 mg/kg) was
      significantly superior to the comparator regimen vancomycin (-4.54 +/- 1.12
      log(10)/mL for daptomycin versus -3.43 +/- 1.17 log(10)/mL for vancomycin).
      Daptomycin managed to sterilize 6 out of 10 CSFs compared with 4 out of 10 for
      vancomycin. The penetration of daptomycin into inflamed meninges was
      approximately 5% and approximately 2% into non-inflamed meninges. CONCLUSIONS:
      The superior bactericidal activity of daptomycin was confirmed in vivo and in
      time-killing assays in vitro.

PMID- 16459346
TI  - Reducing ischaemic damage in rodent ovarian xenografts transplanted into
      granulation tissue.
AB  - BACKGROUND: Anti-cancer therapies frequently lead to ovarian damage and impaired
      fertility. To preserve fertility, cryopreservation and subsequent transplantation
      of the ovaries have been suggested. One of the challenges in ovarian graft
      transplantation is overcoming the initial ischaemic damage that depletes a
      significant fraction of the oocyte pool. METHODS AND RESULTS: Follicular survival
      in ovarian grafts was examined by magnetic resonance imaging (MRI) and
      fluorescence microscopy in a model system in which rat ovaries were transplanted
      into nude mice. Transplantation into angiogenic granulation tissue created during
      wound healing shortened the ischaemic period by 24 h and significantly increased
      the pool of healthy primordial follicles and the perfused area of the
      transplanted grafts. Functional blood vessels were detected within the grafts as
      early as 2 days after transplantation. Gain of function was demonstrated both by
      growth of the grafts and by the hormonal influence on the host uteri. CONCLUSION:
      Implantation of ovarian grafts into an angiogenic granulation tissue improved
      graft vascularization and follicular survival. This procedure/treatment may be
      used for reducing the ischaemic damage in ovarian transplants, thus prolonging
      graft functionality and increasing the yield of oocytes that can be easily
      recovered for fertilization.

PMID- 16459347
TI  - Spontaneous conceptions and live birth after heterotopic ovarian transplantation:
      is there a germline stem cell connection?
AB  - Ovarian cryopreservation and transplantation is an emerging technology to
      preserve fertility in women and children undergoing cancer treatment. Recent
      reports of live births after orthotopic transplantation raised hopes for the
      future success of this procedure. However, doubts remained whether the reported
      pregnancies were as a result of resumed function in the remaining ovary. We
      recently performed an autologous heterotopic ovarian transplantation in a 32-year
      old Hodgkin lymphoma survivor who was menopausal for 2.5 years as a result of a
      preconditioning chemotherapy given before a hematopoietic stem cell transplant.
      Subsequent to the transplantation, the patient conceived twice within 3 months
      and delivered a healthy female child at 40 weeks of gestation. The occurrence of
      spontaneous pregnancies after heterotopic ovarian transplantation highlights the
      need for caution when interpreting the source of pregnancies in recipients with
      intact ovaries. On the other hand, the temporal relationship between the ovarian
      transplant and the spontaneous resumption of ovarian function and pregnancies in
      previously menopausal women is intriguing, especially in the light of recent
      reports of germ cell renewal and migration from the bone marrow to the ovary in
      rodents.

PMID- 16459348
TI  - Limiting the number of injected oocytes to three impairs ICSI outcomes in
      patients with nonobstructive azoospermia.
AB  - BACKGROUND: Since March 2004, only a maximum of three oocytes were allowed to be
      subjected to ICSI at one time in Italy. A previous study failed to show an impact
      of this restriction on fresh embryo transfer outcomes. The objective of this
      study was to compare ICSI outcomes before and after this restriction in patients
      with nonobstructive azoospermia. METHODS: Patients underwent testicular sperm
      extraction followed by ICSI. Biological (fertilization rate and the percentage of
      good-morphology zygotes and embryos) and clinical (clinical pregnancy and
      implantation rates) outcomes of the last 100 ICSI attempts before the restriction
      and outcomes of the first 100 ICSI attempts after the restriction were compared.
      RESULTS: Despite comparable fertilization rates (58.8% versus 59.2%; P > 0.05),
      there was a significant decrease in the percentage of good-morphology zygotes
      (41.1% versus 88.4%; P < 0.05) and embryos (36.7% versus 74.0%; P < 0.05) in the
      cohort of embryos transferred, clinical pregnancy rate (22.7% versus 42.4%; P <
      0.05) and cumulative pregnancy rate from fresh and frozen embryo transfers (22.7%
      versus 53.5%; P < 0.05) after the restriction. CONCLUSION: The oocyte number
      restriction reduces dramatically the chance of achieving a clinical pregnancy in
      cases of nonobstructive azoospermia.

PMID- 16459349
TI  - Paternal sperm concentration and growth and cognitive development in children
      born with a gestational age more than 32 weeks after assisted reproductive
      therapy.
AB  - BACKGROUND: A possible impact of paternal sperm quality on the outcome in
      children born after assisted reproductive technologies, especially ICSI, has been
      discussed. The objective of this study was to assess whether sperm concentration
      has any influence on growth and cognitive development in children born with a
      gestational age more than 32 weeks after ICSI or IVF. METHODS: Singleton children
      born after ICSI (n = 492) or IVF (n = 265) from five European countries were
      examined at age 5 years. The ICSI group was divided into five subgroups according
      to paternal sperm origin and sperm concentration: (1) epididymal and testicular
      sperm group, (2) ejaculated sperm < 1 x 10(6)/ml, (3) ejaculated sperm 1-4.99 x
      10(6)/ml, (4) ejaculated sperm 5-19.99 x 10(6)/ml and (5) ejaculated sperm > or =
      20 x 10(6)/ml. The IVF group was divided into two subgroups: (1) < 20 x 10(6)/ml
      and (2) > or = 20 x 10(6)/ml. Growth parameters at birth and age 5 were
      evaluated. Cognitive development was assessed with the Wechsler Preschool and
      Primary Scale of Intelligence-Revised. RESULTS: No significant difference was
      found for gestational age, birth weight and birth weight standard deviation
      scores (SDS) between the ICSI and IVF sperm groups. No significant difference in
      height and weight at age 5 or SDS weight or height or BMIs at age 5 was found.
      There was no significant difference in total intelligence quotient (IQ)-
      performance or verbal IQ--between the groups. CONCLUSION: We found no indication
      that growth and cognitive development in ICSI and IVF children differed depending
      on paternal sperm concentration.

PMID- 16459350
TI  - Effects of estrogenic xenobiotics on human and mouse spermatozoa.
AB  - OBJECTIVE: To investigate human sperm responsiveness to the estrogenic xenobiotic
      genistein and seek further information regarding the mechanism of action of
      estrogenic xenobiotics using mouse spermatozoa. METHODS: Uncapacitated human
      spermatozoa were incubated with genistein and assessed using chlortetracycline
      (CTC) fluorescence. CTC was also used to evaluate mouse sperm responses to
      daidzein and combinations of genistein, 8-prenylnaringenin and nonylphenol.
      Several steroids were tested to determine structure-function relationships, and
      possible involvement of cAMP and G proteins in responses was also investigated.
      RESULTS: Genistein significantly accelerated capacitation and acrosome loss in
      human spermatozoa, with 1, 10 and 100 nmol/l being equally effective. In mouse
      spermatozoa, daidzein produced significant responses, and combinations of
      xenobiotics at low concentrations were more effective than used singly. The
      compounds appear to act at the cell surface, and responses to three different
      steroids were nonidentical. A protein kinase-A inhibitor blocked responses to
      xenobiotics, while genistein and nonylphenol significantly stimulated cAMP
      production. Pertussis toxin and dideoxyadenosine blocked responses, suggesting
      involvement of inhibitory G proteins and membrane-associated adenylyl cyclases.
      CONCLUSION: Human and mouse sperm responses to genistein are very similar, but
      human gametes appear to be even more sensitive. The mechanism of action may
      involve unregulated stimulation of cAMP production, leading to significant
      acrosome loss, undesirable because already acrosome-reacted cells are
      nonfertilizing. Xenobiotics were even more effective in combination. Since
      simultaneous exposure to low concentrations of multiple xenobiotics is likely to
      occur in animals and humans, further investigation is needed to determine whether
      this could impair fertility.

PMID- 16459351
TI  - Alterations in the phenotype and function of immune cells in ovariectomy-induced
      osteopenic mice.
AB  - BACKGROUND: Within the last few years, much evidence has been presented on the
      involvement of the immune system in certain types of bone loss, such as activated
      T cells in rheumatoid arthritis and in periodontitis. Estrogen deficiency induces
      bone loss; however, how this deficiency affects the immune system has not been
      sufficiently studied. METHODS: To evaluate the effects of estrogen withdrawal on
      the status and functionality of the immune system, mice were ovariectomized or
      sham-operated, and 5 weeks after surgery, when osteopenia had developed, several
      parameters were analysed in spleen and in bone marrow. We analysed bone turnover,
      cell phenotype by flow cytometry, cell function by cell proliferation assays, and
      the expression of several genes related to the process. RESULTS: Five weeks after
      ovariectomy, augmented osteoclastogenesis persisted in the bone marrow. In
      addition, the ovariectomized mice had more B-cells and CD3+ T-cells expressing
      the receptor activator of NF-kappaB ligand (CD3+/RANKL+). The ovariectomized mice
      had lower serum alkaline phosphatase activity, a normal amount of T cells, lower
      percentages of CD11b+ and CD51+ cells in the bone marrow, and a lower serum
      interferon-gamma level compared with sham-operated controls. CONCLUSIONS: The
      data suggest that, 5 weeks after ovariectomy, bone turnover remains imbalanced,
      with increased osteoclastogenesis and a decreased rate of bone formation.
      Moreover, there is an increase in B-cell formation, with normal and decreased
      percentages of T cells and myelomonocytic cells (CD11b+), respectively, in the
      bone marrow. Decreased serum interferon-gamma levels could be involved in the
      increased osteoclastogenesis found in the present work.

PMID- 16459352
TI  - Determinants of emotional distress in women with polycystic ovary syndrome.
AB  - BACKGROUND: The goals were to analyse the incidence of mental distress in women
      with untreated polycystic ovary syndrome (PCOS) using self-report measures, to
      characterize PCOS patients at risk for psychiatric disease with regard to
      sociodemographic and clinical characteristics, and to assess the impact of
      emotional distress on quality of life. METHODS AND RESULTS: Complete metabolic,
      hormonal, clinical and self-report psychological data [emotional distress,
      Symptom Check List 90 (SCL-90-R); quality of life, Short-Form Health Survey 36
      (SF-36); sexual satisfaction, visual analogue scales; sociodemographic data] were
      obtained from n = 143 untreated women with PCOS. Prior psychiatric diagnoses were
      exclusionary. Twenty-two patients (15.4%) had a possible psychological disorder,
      based on SCL-90-R global severity index (GSI) scores > or =63 (SCL cases). SCL
      cases had significantly elevated body mass index (BMI), but did not differ from
      SCL non-cases in other clinical, endocrine, metabolic or sociodemographic
      variables. Stepwise multiple regression analyses identified GSI as a significant
      predictor of SF-36 Psychological Sum score, along with age and current wish to
      conceive (R2 = 0.47); the SF-36 Physical Sum score was predicted by BMI and
      education (R2 = 0.27), but not GSI. CONCLUSIONS: Psychiatric illness may go
      undetected in a proportion of PCOS patients. Although the majority of patients
      exhibit subclinical levels of psychological disturbances, emotional distress
      together with obesity lead to large decrements in quality of life in PCOS.

PMID- 16459353
TI  - Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis,
      and remodeling in the rat heart.
AB  - Aging is characterized by loss of myocytes, remodeling, and impaired contractile
      function in the heart. The rate of programmed cell death, or "apoptosis," in the
      left ventricle increases with age, and contributes to a 30% reduction in
      myocytes. Aging may preferentially target the Bcl-2 pathway of apoptosis in the
      heart. Exercise can protect cardiac function of the aging heart, although the
      mechanisms are poorly understood. We tested the hypothesis that 12 wk of exercise
      training would attenuate age-induced increases in remodeling, apoptosis, and
      Bax/Bcl-2 ratio in rat left ventricle. We found that exercise training provided
      significant protection against loss of cardiac myocytes, reduction in number of
      myonuclei, reactive hypertrophy of remaining myocytes, and increased connective
      tissue in left ventricle of the aging rat heart. Exercise training significantly
      attenuated age-induced increases of apoptosis in the left ventricle, as indicated
      by lower DNA fragmentation, TUNEL-positive staining, and caspase-3 cleavage, when
      compared with left ventricles from the age-matched sedentary group. Further,
      exercise training in the aging reduced caspase-9 levels and Bax/Bcl-2 ratio by
      lowering Bax protein expression while increasing Bcl-2 levels. These are the
      first data to demonstrate protective effects of endurance exercise training
      against elevated apoptosis and remodeling in the aging heart.

PMID- 16459354
TI  - [Detoxication gene polymorphism and susceptibility to sporadic motor neuron
      disease in Russian population].
AB  - Motor neuron disease (MND) is caused by selective degeneration of motor neurons
      of the cerebral cortex, brain stem and spinal cord. Many genetic systems are
      thought to be involved in pathogenesis of this complex disease. A significant
      etiological factor of MND may be oxygen free radicals, which damage neuronal
      cells when they are present in high concentrations. Detoxication processes
      resulting in the formation of free radicals, which subsequently transformed into
      nontoxic products, are also critical for the disease development. The major
      participants of these processes are cytochromes P-450 (CYP2E1, CYP2D6),
      glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT2).
      To investigate a role of genes of detoxication system in development of MND, we
      study polymorphisms in these genes in 72 patients with MND from Moscow and
      controls from Russia. Significant statistical differences have been found in
      frequency of the alleles CYP2E1*1D, CYP2D6*4 and GSTM1(0/0) and genotypes
      homozygous for GSTM1 (0) between the study and control groups. The analysis of
      GSTT1, GSTP1 and NAT1 gene polymorphisms has revealed no between-group
      differences in distribution of different alleles and genotypes. The GSTP1*A/
      GSTP1*A genotype was associated with a classical upper and lower motor neuron
      involvement and the GSTP1*A allele with predominant lower and upper motor neuron
      involvement.

PMID- 16459355
TI  - Reviewing for KI: is it encoded in your DNA?

PMID- 16459356
TI  - Evaluation of sugarcane by-product pressmud as a manure in carp culture.
AB  - The effectiveness of pressmud, a sugarcane by-product, was tested as a manure in
      the production of natural food and carp, by conducting two experiments. The first
      experiment, of 5 weeks duration, examined the effect of pressmud addition on
      water quality and natural food production. This study was carried out in
      fibreglass tubs (1.54 m3) with a 5 cm mud layer, employing pressmud at dosages of
      5000, 10,000 and 15,000 kg ha(-1) for treatments T1, T2 and T3, respectively.
      Unfertilized tubs served as control (T0). The second experiment of 120-day
      duration to study the effect on growth, survival and quality of common carp was
      conducted in 25 m2 cement tanks with 15 cm-mud bottom, using the same dosages of
      pressmud. The control tanks in this experiment were manured with cattle dung at
      10,000 kg ha(-1) (T0). Application of pressmud enhanced (P < 0.05) natural food
      production, with the greatest effect noted in treatment T3. Fish growth was
      significantly greater (P < 0.05) in treatments T2 and T3, there being no
      difference in growth between the control (T0) and 5000 kg pressmud treatment
      (T1). The greatest survival and production were obtained under treatment T2,
      which indicates that the dosage of 10,000 kg ha(-1) pressmud is optimal for carp
      culture. A significant effect (P < 0.05) of pressmud on carcass protein was
      observed. Organoleptic quality of both raw flesh and cooked meat of carp was not
      affected (P > 0.05) by pressmud treatment.

PMID- 16459357
TI  - T cells and T-cell receptors in acute renal failure.
AB  - T cells are activated by antigen-independent as well as antigen-dependent
      mechanisms during ischemia-reperfusion injury to the kidney. In the current
      issue, a study by Savransky et al. suggests that antigen-dependent activation of
      T-cell receptors further contributes to the pathogenesis of ischemia-reperfusion
      injury.

PMID- 16459360
TI  - Reactions to the Hwang scandal.

PMID- 16459359
TI  - Molecular basis for adaptive responses during chemically induced hepatotoxicity.

PMID- 16459361
TI  - Reactions to the Hwang scandal.

PMID- 16459362
TI  - Reactions to the Hwang scandal.

PMID- 16459363
TI  - Questions about forensic science.

PMID- 16459364
TI  - Questions about forensic science.

PMID- 16459365
TI  - Questions about forensic science.

PMID- 16459366
TI  - Incidental angiographic diagnosis of uninfected perforated aortic cusp.

PMID- 16459367
TI  - Sudden cardiac death in athlete with anomalous single coronary artery.

PMID- 16459368
TI  - Would artificial wombs produce more harm than good?

PMID- 16459369
TI  - Some critical comments on oocyte-assisted reprogramming.

PMID- 16459370
TI  - Catholic hospitals in the new evangelization.

PMID- 16459371
TI  - A proposed novel treatment for rape victims.

PMID- 16459372
TI  - Are teratomas embryos or non-embryos?: a criterion for oocyte-assisted
      reprogramming.

PMID- 16459373
TI  - Blessed are the pluripotent: New Testament guidance for the embryonic stem cell
      debate.

PMID- 16459374
TI  - Sex reassignment surgery for transsexuals: an ethical conundrum?

PMID- 16459375
TI  - Marriage and the prophylactic use of condoms.

PMID- 16459376
TI  - How a hylomorphic metaphysics constrains the abortion debate.

PMID- 16459377
TI  - Consensus statement on dignity in illness, disability, and dying: and a response
      to the UNESCO Universal Draft Declaration on Bioethics and Human Rights.

PMID- 16459378
TI  - Rights talk and its remedies: the jurisprudence of Mary Ann Glendon.

PMID- 16459379
TI  - In South Korea, ethics questions prompt a stem-cell pioneer to resign a top post.

PMID- 16459380
TI  - New California law stiffens data-protection rules for research on human subjects.

PMID- 16459381
TI  - Cell divisions.

PMID- 16459382
TI  - A nation's pride turns to shame.

PMID- 16459383
TI  - Life, death, and biocultural literacy.

PMID- 16459384
TI  - A retreat from reason? The Catholic church and scientific progress.

PMID- 16459385
TI  - Living with sin: the Catholic hierarchy and reproductive rights in the
      Philippines.

PMID- 16459386
TI  - Gaining ground: despite political and religious opposition, Latin American
      activists force advances in reproductive rights.

PMID- 16459387
TI  - Contraceptive emergency: Catholic hospitals overwhelmingly refuse to provide EC.

PMID- 16459388
TI  - 'Reprogenetics': hype, phobia and choice: an unreserved advocate of new
      reproductive technologies argues his case.

PMID- 16459389
TI  - What if I just say "a pox on both your houses"?

PMID- 16459390
TI  - Let life shape personality, not genetics.

PMID- 16459391
TI  - The genetic fallacy: perfect genes do not eliminate schmucks.

PMID- 16459392
TI  - Trusting common sense.

PMID- 16459393
TI  - The vagaries of government regulation.

PMID- 16459394
TI  - Caveat lector: the true results of polling are in the small print.

PMID- 16459395
TI  - Informed consent: between ethics and law.

PMID- 16459396
TI  - Address of John Paul II to the participants at the International Congress on
      "Life-sustaining treatments and the vegetative state: scientific advances and
      ethical dilemmas".

PMID- 16459397
TI  - Challenges for Christians in Europe in medicine and health care.

PMID- 16459398
TI  - Bioethics in UNESCO.

PMID- 16459399
TI  - From the right to die to the duty to die? Joint Declaration of the Episcopal
      College of the Church of England and the Catholic Episcopal Conference of England
      and Wales given to the Committee of the House of Lords on the Bill on Assisted
      Death for the Terminally Ill in the United Kingdom, 2 September 2004.

PMID- 16459400
TI  - Reasonable partiality and animal ethics.
AB  - Moral psychology is often ignored in ethical theory, making applied ethics
      difficult to achieve in practice. This is particularly true in the new field of
      animal ethics. One key feature of moral psychology is recognition of the moral
      primacy of those with whom we enjoy relationships of love and friendship--philia
      in Aristotle's term. Although a radically new ethic for animal treatment is
      emerging in society, its full expression is severely limited by our exploitative
      uses of animals. At this historical moment, only the animals with whom we enjoy
      philia--companion animals--can be treated with unrestricted moral concern. This
      ought to be accomplished, both for its own sake and as an ideal model for future
      evolution of animal ethics.

PMID- 16459401
TI  - Reasonable partiality in professional ethics: the moral division of labour.
AB  - Attention is given to a background idea that is often invoked in discussions
      about reasonable partiality: the idea of a moral division of labour. It is not
      only a right, but also a duty for professionals to attend (almost) exclusively to
      the interests of their own clients, because their partial activities are part of
      an impartial scheme providing for an allocation of professional help to all
      clients. To clarify that idea, a difference is made between two kinds of division
      of labour, a technical one and a social one. In order to assess the applicability
      of the idea of a moral division of labour to professional ethics, journalism is
      contrasted with other professions.

PMID- 16459402
TI  - Reasonable partiality in professional relationships.
AB  - First, two aspects of the partiality issue are identified: (1) Is it
      right/reasonable for professionals to favour their clients' interests over either
      those of other individuals or those of society in general? (2) Are special non
      universalisable obligations attached to certain professional roles? Second, some
      comments are made on the notions of partiality and reasonableness. On partiality,
      the assumption that only two positions are possible--a detached universalism or a
      partialist egoism--is challenged and it is suggested that partiality, e.g. to
      family members, lies between these two positions, being neither a form of egoism,
      nor of impersonal detachment. On reasonableness, it is pointed out that
      'reasonable' is an ambiguous concept, eliding the notions of the 'morally right'
      and the 'rational.' Third, a series of practical examples are taken from
      counselling, medicine, law, education and religious practice and some common
      principles are abstracted from the cases and discussed. These include truth
      telling, confidentiality, conflicts of interest between clients and particular
      others and between clients and society. It is concluded that while partiality can
      be justified as a useful tool in standard cases, particular circumstances can
      affect the final verdict.

PMID- 16459403
TI  - The moral contours of empathy.
AB  - Morally contoured empathy is a form of "reasonable partiality" essential to the
      healthy care of dependents. It is critical as an epistemic aid in determining
      proper moral responsiveness; it is also, within certain richly normative roles
      and relationships, itself a crucial constitutive mode of moral connection. Yet
      the achievement of empathy is no easy feat. Patterns of incuriosity imperil
      connection, impeding empathic engagement; inappropriate "empathic" engagement, on
      the other hand, can result in self-effacement. Impartial moral principles and
      constraints offer at best meager protection against these perils, and hence serve
      poorly in securing morally contoured empathy. More nuanced and practical guidance
      should be sought in normatively substantive conceptions of our roles and
      relationships and their defining moral stakes. These, joined with more abstract
      moral tools, can facilitate rich, narratively textured interpretations of
      morality's demands. While the content of our normative conceptions must be
      continually debated, engaging in this debate is vital to the achievement of
      proper empathy, and thus to effective, respectful, morally healthy care of
      dependents.

PMID- 16459404
TI  - Directed altruistic living organ donation: partial but not unfair.
AB  - Arguments against directed altruistic living organ donations are too weak to
      justify a ban. Potential donors who want to specify the non-related person or
      group of persons to receive their donated kidney should be accepted. The
      arguments against, based on considerations of motivation, fairness and (non
      )anonymity (e.g. those recently cited by an advisory report of the Dutch Health
      Council), are presented and discussed, as well as the Dutch Government's
      response. Whereas the Government argues that individuals have authority with
      regard to the allocation of their organs, partial considerations have not been
      sufficiently explored. In addition, it is argued that partial relationships
      govern human life, are significant and should be valued highly. These
      relationships are at the core of accepted living kidney donation between
      relatives (family members, partners, friends). Respecting the particular act of
      living donation goes beyond respect for autonomy; it touches upon our personal
      and social identity. Donation, e.g. of a kidney, is not undertaken strictly for
      the benefit of the recipient, but also to meet the moral standards we wish to set
      for ourselves. This consideration, rooted in a view of moral identity, provides
      the basis for many forms of directed donation that are both partial and
      justified. If the importance of this is not recognized, social policies can be
      neither adequate nor effective.

PMID- 16459405
TI  - Stemming the tide of cloning.

PMID- 16459406
TI  - Orphans by design.

PMID- 16459407
TI  - BiDil: false promises: faulty statistics and reasoning have lead to the first
      "racial medicine".

PMID- 16459408
TI  - China's gene therapy drug: do Shenzen SiBiono Gen-Tech's claims hold up?

PMID- 16459409
TI  - Cloning in America: the Genetics and Public Policy Center surveys the nation.
AB  - The Genetics and Public Policy Center, a part of the Phoebe R. Berman Bioethics
      Institute at Johns Hopkins University, compiled the survey information found in
      the following article for a 2005 publication entitled "Cloning: A Public Policy
      Report." This article is a summation of the Genetics and Public Policy Center's
      findings on the public opinion of cloning, stem cell research, and the legal
      environment which regulates these fields. The original report can be found in it
      entirety at www.dnapolicy.org. The author of this article is a freelance writer
      who compiled the report on behalf of The Genetics and Public Policy Center.

PMID- 16459410
TI  - Translating ethics into law: duties of care in health research involving humans.

PMID- 16459411
TI  - The long arm of administrative law: applying administrative law principles to
      research ethics boards.

PMID- 16459412
TI  - Consent revisited: points to consider.

PMID- 16459413
TI  - Federal regulation of REB review of clinical trials: a modest but easy step
      towards an accountable REB review structure in Canada.

PMID- 16459414
TI  - Ethics review of multi-centre clinical trials in Canada.

PMID- 16459415
TI  - Legal and ethical issues associated with patient recruitment in clinical trials:
      the case of competitive enrolment.

PMID- 16459416
TI  - Evidence-based practice of research ethics review?

PMID- 16459417
TI  - A cultural understanding of research ethics governance.

PMID- 16459418
TI  - Research governance, bio-politics and political will: recent lessons from
      Newfoundland and Labrador.

PMID- 16459419
TI  - Professional responsibility and the protection of human subjects of research in
      Canada.

PMID- 16459420
TI  - Research ethics across the 49th parallel: the potential value of pilot testing
      "equivalent protections" in Canadian research institutions.
AB  - Canada and the United States share the world's largest trade partnership and an
      increasing concern about divergent regulatory approaches to common industries.
      Canadian research institutes receive more research funding from the U.S. National
      Institutes of Health than any other country, much of it to fund multi-centre and
      collaborative research between the two countries. Because of these close economic
      and research ties, and the extensive similarities between the two countries in
      the review and oversight of ethics in human subjects research, we propose that
      Canada would be an ideal country for a pilot-test of the feasibility of
      "equivalent protections," a U.S. regulation that permits comparison of
      protections for human subjects between institutions in the two countries. The
      "equivalent protections" has been advocated by various bodies in the United
      States as a potentially beneficial mechanism for improving oversight of foreign
      trials. As well, we argue that "equivalent protections" could prove to be
      valuable for Canada in five specific ways: (1) by potentially reducing
      administrative burden on Canadian research institutions administering U.S.
      federal research funding; (2) by creating symbolic value of an explicit
      recognition by the United States that procedures normally followed for the
      protection of human subjects in Canadian research institutions are at least
      equivalent to those provided by the U.S. regulations; (3) by lowering the
      opportunity cost of investing in research in Canada; (4) by affording Canada an
      opportunity to enhance its leadership role in international research by offering
      an alternative to the U.S. regulatory model for the protection of human subjects;
      and (5) by providing a model for how the idea of equivalent protections might be
      addressed for research funded by Canadian agencies but conducted in other
      countries.

PMID- 16459421
TI  - Contrasting modes of governance for the protection of humans and animals in
      Canada: lessons for reform.

PMID- 16459422
TI  - Evaluation of immunotoxic and immunodisruptive effects of inorganic arsenite on
      human monocytes/macrophages.
AB  - A trivalent inorganic arsenic, arsenite, has been causing chronic inflammation in
      humans through the consumption of contaminated well water. The total peripheral
      blood arsenic concentrations of chronic arsenic-exposed patients, who had
      inflammatory-like immune responses, are less than 1 microM, thus, nM
      concentrations may be very important regarding the chronic inflammatory effects
      by arsenite. However, there are few reports about the biological effects of low
      concentrations of arsenite in mammalian cells, especially in normal immune
      effector cells. In this study, we examined whether arsenite has any biological
      and/or toxicological effects on the differentiation of human peripheral blood
      monocytes into macrophages using the colony-stimulating factor (CSF) in vitro
      compared with that of other metallic compounds, and found that arsenite
      sensitively inhibited the CSF-induced in vitro maturation of monocytes into
      macrophages at nM levels, and it also induced small, nonadhesive and CD14
      positive abnormal macrophage generation from monocytes with granulocyte
      macrophage CSF (GM-CSF) at 50-500 nM without cell death. The addition of other
      metallic compounds, including chromium, selenium, mercury, cadmium, nickel,
      copper, zinc, cobalt, manganese and other human pentavalent arsenic metabolites,
      such as inorganic arsenate, monomethylarsonic acid and dimethylarsinic acid,
      could not induce the same abnormal cell generation from monocytes with CSFs at
      any concentration and any additional time schedules; they showed only simple
      cytolethality in monocytes and macrophages at any concentration and any
      additional time schedules; they showed only simple cytolethality in monocytes and
      macrophages at n-mM levels accompanied by cell death. This work may have
      implications in the arsenic-induced chronic inflammation in humans.

PMID- 16459423
TI  - Trends in collection, use and disclosure of personal information in contemporary
      health research: challenges for research governance.

PMID- 16459424
TI  - Commentary: an independent voice?: conflicts of interest and research on ethical,
      legal and social issues.

PMID- 16459425
TI  - Ethics and policy perspectives on personalized medicine in the post-genomic era.
AB  - The completion of the human genome project and the accompanying biotechnological
      revolution hold great promise for the creation of pharmaceutical agents to combat
      not only previously incurable diseases, but also those for which therapeutics
      exist, yet they either cause severe adverse effects or exhibit no benefit in
      subsets of the population. In many instances variation in therapy response can be
      attributed to genetic differences, more particularly single nucleotide
      polymorphism (SNPs). Detection of the genetic differences which affect drug
      response, commonly referred to as pharmacogenomics, may result in further
      classification of diseases, and consequently, the development of 'personalized'
      therapies. While of potential great benefit, the widespread use of
      pharmacogenomic data poses social, ethical, and economic risks that need to be
      addressed by regulatory agencies such as the Food and Drug Administration (FDA).
      This paper explores some of the common problems associated with the use of
      pharmacogenomic data including validation of the data, patient confidentiality,
      social stratification, economic risks faced by pharmaceutical and insurance
      companies, and offers suggestions for regulatory procedures to ensure the
      appropriate use of the data in drug development and clinical trials.

PMID- 16459426
TI  - Conflicts of interest in medical research: how much conflict should exceed legal
      boundaries?
AB  - This article addresses the current plague of financially conflicted research from
      various perspectives including the research community, the medical community,
      patients/subjects, the Food and Drug Administration (F.D.A.), and other
      government agencies. Part one lays out the current conflicts of interest within
      medical research. Part two explains the actual and potential effects of these
      conflicts, highlighting the conflict of interest associated with the death of
      Jesse Gelsinger. Part three describes how conflicts of interest are currently
      regulated by government agencies and within individual institutions. Lastly, part
      four concludes by recommending a system of seven balanced reform measures that
      protect research subjects and the scientific integrity of medical research while
      encouraging scientific progress.

PMID- 16459427
TI  - Judge declares pre-embryo is human.

PMID- 16459428
TI  - The practical logic of reasonableness: an ethnographic reconnaissance of a
      research ethics committee.

PMID- 16459429
TI  - Ethical considerations in research on preventing mother-to-child HIV
      transmission.
AB  - Preventing mother to child transmission of HIV (PMTCT) is an issue that has come
      to the forefront in the global response to the HIV pandemic. This is particularly
      true for countries in sub-Saharan Africa and in Asia, which account for the
      largest proportion of people living with HIV. The relative success of PMTCT
      efforts to date have encouraged policy makers and donors alike to push for a
      rapid scaling up of the program in countries with a high prevalence of HIV.
      However, it is increasingly apparent that the relative success of the program has
      been at the expense of the rights and well-being of the mothers who are the
      primary recipients of the intervention. This article examines the nature and
      scope of the 'research enterprise' in PMTCT and shows how it has influenced
      intervention design and policy in India. It will also include the voices of
      'target' women to convey the extent to which the research has impacted on their
      lives. Finally, this article indicates priorities for research that can help the
      situation of women as well as reduce MTCT of HIV.

PMID- 16459430
TI  - Medical research and involuntary mental health patients: implications of proposed
      changes to legislation in Victoria.

PMID- 16459431
TI  - Medical research and participants with disabilities.

PMID- 16459432
TI  - Stem cell debacle: the downfall of South Korea's star researcher holds a vital
      lesson.

PMID- 16459434
TI  - Breach of trust: events in South Korea have highlighted a deep-seated problem.

PMID- 16459433
TI  - Rewriting your past: drugs that rid people of terrifying memories could be a
      lifeline for many. But could they have a sinister side too?

PMID- 16459435
TI  - Cloning crisis goes from bad to worse.

PMID- 16459436
TI  - A scale to assess attitudes toward euthanasia.
AB  - The topic of euthanasia has been a matter of public debate for several decades.
      Although empirical research should inform policy, scale measurement is lacking.
      After analyzing shortcomings of previous work, we offer a systematically designed
      scale to measure attitudes toward euthanasia. We attempt to encompass previously
      unspecified dimensions of the phenomenon that are central to the euthanasia
      debate. The results of our pretest show that our attitude towards euthanasia
      (ATE) scale is both reliable and valid. We delineate active and passive
      euthanasia, no chance for recovery and severe pain, and patient's autonomy and
      doctor's authority. We argue that isolating these factors provides a more robust
      scale capable of better analyzing sample variance. Internal consistency is
      established with Cronbach's alpha=.871. Construct external consistency is
      established by correlating the scale with other predictors such as race and
      spirituality.

PMID- 16459437
TI  - Health care coverage: whose responsibility?

PMID- 16459438
TI  - Potentialism and the value of an embryo.

PMID- 16459439
TI  - Biomedicalizing kinship: sperm banks and the creation of affinity-ties.

PMID- 16459440
TI  - Sterilizing filtration of gases. Technical report no. 40. Parenteral Drug
      Association.

PMID- 16459441
TI  - Effects of porosity on the fatigue performance of polymethyl methacrylate bone
      cement: an analytical investigation.
AB  - Porosity has been shown to affect the fatigue life of bone cements, but, although
      vacuum mixing is widely used to reduce porosity in the clinical setting, results
      have been mixed and the effects of porosity are not well understood. The aim of
      this study was to investigate the effects of porosity using stress analysis and
      fracture mechanics techniques. The stress concentrations arising at voids in test
      specimens were found using analytical solutions and boundary element methods. The
      fatigue life of specimens containing voids of various sizes was predicted using
      fracture mechanics techniques. For spherical voids that do not occupy a
      significant proportion of the cross-section, the resulting stress concentration
      is independent of void size and too small to account for the observed crack
      initiation. Cracks must therefore initiate at additional stress raisers such as
      radiopacifier particles or additional voids. For large voids, the stress
      increases as the remaining cross-section of the specimen decreases, and this may
      account for much of the observed reduction in fatigue strength in hand-mixed
      cement. Although crack initiation may be largely independent of void size, there
      is an effect on crack growth rate. Cracks are predicted to grow faster around
      larger voids, since they remain in the stress concentration around the void for
      longer. This effect may account for the relationship between porosity and fatigue
      life that has been observed in samples without large voids. Since porosity
      appears to affect crack growth more than initiation, it may be less damaging in
      high-cycle clinical fatigue, which may be predominantly initiation controlled,
      than in short laboratory tests.

PMID- 16459442
TI  - Validation of the small-punch test as a technique for characterizing the
      mechanical properties of acrylic bone cement.
AB  - This paper examines the validity of using the small-punch test technique as a
      means of quantifying the mechanical properties of acrylic bone cement under
      different test conditions. The elastic moduli calculated using the small-punch
      test method were compared with data measured using the international standard for
      acrylic bone resin, ISO 5833. Conclusions from the study indicate that the small
      punch test is a reproducible miniature specimen test method that can be used to
      characterize the mechanical properties of retrieved acrylic bone cement as used
      in total joint replacement surgery. Moreover, the test conditions were found to
      influence the elastic modulus of acrylic bone cement. The test temperature had a
      greater effect on the elastic behaviour of the bone cement than the test medium.

PMID- 16459443
TI  - Influence of hyaluronic acid on the time-dependent friction response of articular
      cartilage under different conditions.
AB  - Therapeutic lubricant injections of hyaluronic acid are a relatively recent
      treatment for osteoarthritis. Their efficacy, however, in vivo has been subject
      to much debate. Frictional properties of cartilage-cartilage contacts under both
      static and dynamic loading conditions have been investigated, using healthy
      cartilage and cartilage with a physically disrupted surface, with and without the
      addition of a therapeutic lubricant, hyaluronic acid. Most of the cartilage
      friction models produced typical time-dependent loading curves, with a rise in
      static friction with loading time. For the dynamic loading conditions the rise in
      friction with loading time was dependent on the spatial (and time) variation in
      the load on the cartilage plate. For sliding distances of 4 mm or greater, when
      the cartilage plate was unloaded during sliding, the dynamic friction remained
      low whereas, with shorter sliding distances, the dynamic friction increased with
      increasing loading time. Static friction was higher than dynamic friction (under
      the same tribological conditions). The 'damaged' cartilage models produced higher
      friction than healthy cartilage under equivalent tribological conditions. It was
      shown that hyaluronic acid was an effective boundary lubricant for articular
      cartilage under static conditions with both healthy and damaged cartilage
      surfaces. Hyaluronic acid was less effective under dynamic conditions. However,
      these dynamic conditions had low friction values with the control lubricant
      because of the effectiveness of the intrinsic biphasic lubrication of the
      cartilage. It was only under the tribological conditions in which the cartilage
      friction was higher and rising with increasing loading time because of depletion
      of the intrinsic biphasic lubrication, that the role of hyaluronic acid as an
      effective therapeutic lubricant was demonstrated.

PMID- 16459444
TI  - A simple fully integrated contact-coupled wear prediction for ultra-high
      molecular weight polyethylene hip implants.
AB  - A fully coupled contact and wear model was developed in the present study for hip
      implants employing an ultra-high molecular weight polyethylene (UHMWPE) cup in
      combination with a metallic or ceramic femoral head. A simple elasticity equation
      based on the concept of constrained column model was employed to solve the
      contact mechanics between the acetabular cup and the femoral head under the three
      dimensional physiological loading condition. The wear model was based on the
      classical Archard-Lancaster equation in common with all other studies reported in
      the literature. The fully coupled contact and wear model was applied to both
      conventional and cross-linked UHMWPE cups under a wide range of design parameters
      such as the clearance and the femoral head radius. The predicted linear and
      volumetric wear as well as their rates for conventional UHMWPE cups were found to
      be in good agreement with those obtained from a similar analysis by Maxian but
      using the finite element method for the contact mechanics analysis. The predicted
      maximum contact pressure was found to decrease rapidly within the first 10(6)
      cycles, and below the limit to cause plastic deformation within the UHMWPE cup
      with a nominal radial clearance of 0.2 mm. The effect of the clearance between
      the head and the cup on the predicted wear was found to be negligible. For the
      cross-linked UHMWPE cup with relatively large diameters up to 48 mm and a fixed
      outside diameter of 50 mm, the predicted wear, which was found to increase with
      increasing femoral head radius, remained small owing to the small wear factor
      associated with these materials. Furthermore, if the head diameter increases
      beyond 42 mm, a rapid increase in the contact pressure was predicted, owing to
      the decrease in the wall thickness of the cross-linked UHMWPE cup.

PMID- 16459445
TI  - Albumin and fibronectin protein adsorption on CO2-laser-modified biograde
      stainless steel.
AB  - The surface properties of a biomaterial play an essential role in protein
      adsorption, which in turn determines the cellular response to the adsorbed
      surface. In order to obtain a surface that would yield favourable protein
      adsorption for successful cellular response, the surface properties of a biograde
      stainless steel were modified by CO2 laser treatment. An investigation of the CO2
      laser-modified surface properties and the effects thereof on the adsorption of
      human serum albumin (no-cell adhesive) and human plasma fibronectin (cell
      adhesive) was conducted. It was found that the thickness of the adsorbed
      fibronectin layer increased with increasing CO2 laser power density, while the
      thickness of the adsorbed albumin layer decreased with increasing CO2 laser power
      density. The surface roughness and wettability characteristics contributed to the
      observed changes in protein adsorption. The wettability characteristics of the
      biograde stainless steel were found to be the predominant mechanism governing the
      observed change in protein adsorption. Since the wettability characteristics of
      the biograde stainless steel can be modified in an efficient and controllable way
      with the CO2 laser, it is believed that this work presents a demonstrable
      alternative to the techniques currently available for enhancing the
      biocompatibility of biograde stainless steels.

PMID- 16459446
TI  - Indirect selective laser sintering of an apatite-mullite glass-ceramic for
      potential use in bone replacement applications.
AB  - The feasibility of using indirect selective laser sintering (SLS) to produce
      parts from glass-ceramic materials for bone replacement applications has been
      investigated. A castable glass based on the system SiO2 x Al2O3 x P2O5 x CaO x
      CaF2 that crystallizes to a glass-ceramic with apatite and mullite phases was
      produced, blended with an acrylic binder, and processed by SLS. Green parts with
      good structural integrity were produced using a wide range of processing
      conditions, allowing both monolayer and multilayer components to be constructed.
      Following SLS the parts were post-processed to remove the binder and to
      crystallize fully the material, evolving the apatite and mullite phases. The
      parts were heated to 1200 degrees C using a number of different time-temperature
      profiles, following which the processed material was analysed by differential
      thermal analysis, X-ray diffraction, and scanning electron microscopy, and tested
      for flexural strength. An increase in strength was achieved by infiltrating the
      brown parts with a resorbable phosphate glass, although this altered the crystal
      phases present in the material.

PMID- 16459447
TI  - The biomechanics of abfraction.
AB  - The role of occlusal loading in the development of non-carious cervical lesions
      is becoming increasingly prominent. It is suggested that high occlusal loads
      result in large stress concentrations in the cervical region of the teeth. These
      stresses may be high enough to cause disruption of the bonds between the
      hydroxyapatite crystals, eventually resulting in the loss of cervical enamel.
      This article reviews the evidence to support the thesis that occlusal loading can
      contribute to the process of non-carious cervical tooth loss or abfraction. It
      also reviews the potential interactions between occlusal loading and erosion that
      may contribute to non-carious cervical tooth loss.

PMID- 16459448
TI  - Growth monitoring and diagnostic work-up of short stature: an international
      inventorization.
AB  - BACKGROUND/AIMS: Growth monitoring is almost universally performed, but few data
      are available on which referral criteria and diagnostic work-up are used
      worldwide for children with short stature. METHODS: A short questionnaire,
      containing questions on auxological screening and on diagnostic criteria for
      short stature, was sent to all members of the European Society of Paediatric
      Endocrinology (ESPE) and to several pediatric endocrinologists outside Europe.
      RESULTS: Responses were received from 36 countries. In 27 (75%) a child health
      care program existed and in 14 (39%) there was a protocol for referral of
      children with growth retardation. Height for age was mostly used as a referral
      criterion. Sixteen countries (45%) reported having a guideline in secondary
      health care for diagnostic work-up. Although all countries agreed on having
      biochemical, radiological and/or genetic tests in the diagnostic work-up, there
      was a wide variety of recommended tests. CONCLUSIONS: There is little consensus
      on referral criteria and diagnostic work-up of children with short stature among
      industrialized countries. There is a need to establish evidence-based guidelines.

PMID- 16459449
TI  - Correlation between target height and children's height in upper and lower socio
      economic classes in India.
AB  - This study aimed to test the hypothesis that correlation between target height
      and children's height may be less in Indian lower socioeconomic class (LSC) than
      in the upper socioeconomic class (USC). Three hundred and forty-six children from
      USC private schools and 359 children from LSC public schools were measured.
      Measured heights of LSC parents and reported heights of USC parents were used.
      Target height was calculated for both groups. The correlation between children's
      height and target height was significantly stronger in the USC (0.44) as compared
      to the LSC (0.31). Our study showed that the correlation between target height
      and child's height was weaker in the LSC and thus may need more cautious
      interpretation.

PMID- 16459450
TI  - Gender does not influence prepubertal growth velocity during standard growth
      hormone therapy--analysis of United States KIGS data.
AB  - BACKGROUND: Gender is an important determinant that affects the ultimate dose of
      growth hormone (GH) used for replacement in adult GH deficiency (GHD). Women
      require larger doses of GH per body weight to achieve comparable age-adjusted
      serum IGF-I concentrations than do men. OBJECTIVE: To test whether this is
      entirely a sex steroid effect or biologically inherent in gender. PATIENTS AND
      METHODS: We examined growth response to GH (0.25-0.35 mg/kg/week) during the
      first 2 years of therapy in 147 children (44 girls), and in the first 3 years of
      therapy in 83 of these children (23 girls). Children were aged 3-8 years at onset
      of therapy, had peak stimulated GH <10 microg/l, and were reported to be
      prepubertal during the period of analysis. RESULTS: In the relative absence of
      sex steroid, there was no gender difference in growth velocity SDS or gain in
      height SDS during 2 or 3 years of GH therapy. CONCLUSIONS: Inherent gender
      differences in linear growth response to GH prior to puberty may exist, but are
      not evident in the first years of GH therapy at this GH dose.

PMID- 16459451
TI  - Bone density after completion of growth hormone treatment for growth failure.
AB  - Bone density was determined by DEXA scan at completion of growth hormone (GH)
      therapy in 56 (female/male 9/47) young adults who received GH therapy for growth
      failure. The z-scores for total and L2-4 bone density were determined from
      standard curves for age. There was no association of BMD with size. The z-scores
      for total body and L2-4 bone density indicated a disproportionate number with z
      score < -1 SD. Thirty-four percent had z-score < -1 compared to the expected 17%
      for a normal distribution. The markers of bone metabolism, duration of therapy,
      initial or final stimulated GH levels, adult height, and percentage body fat did
      not define those who had decreased bone density. Percentage body fat was
      inversely associated with stimulated GH levels. We conclude that children who
      have completed GH therapy may have decreased bone density at completion of
      therapy and that the GH response to secretagogues does not define this group. The
      significance of this finding will require additional cross-sectional and
      longitudinal studies.

PMID- 16459452
TI  - Clinical and metabolic characteristics of an obese, Dominican, pediatric
      population.
AB  - The prevalence of obesity is particularly high in Black and Latino pediatric
      populations. A limited number of metabolic studies suggest that race plays a role
      in the development of obesity-related co-morbidities. We evaluated clinical and
      metabolic characteristics of 428 obese (mean BMI z-score 2.63) children and
      adolescents ranging in age from 2-20 years, of primarily Dominican ancestry
      attending the obesity clinic at Children's Hospital of New York Presbyterian over
      a 5-year period (1998-2003). Of 193 patients available for detailed metabolic
      analysis, abnormalities were found for elevated systolic blood pressure (19%),
      diastolic blood pressure (11%), total cholesterol (18%), LDL (12%), triglycerides
      (10%), AST (<1%), ALT (4%), low HDL (47%), impaired fasting glucose (5%),
      impaired glucose tolerance 7%, diabetes mellitus by fasting criteria(<1%), and
      metabolic syndrome (14%). Despite extraordinary family histories of obesity and
      diabetes mellitus, the metabolic syndrome and abnormalities of glucose regulation
      were relatively infrequent compared to studies of obese, pediatric Latino
      patients of primarily Mexican and Puerto Rican ancestry. This finding suggests
      that Latinos from different areas of origin may have different risks of obesity
      related conditions.

PMID- 16459453
TI  - The relationship between leptin, metabolic hormones, exercise and body
      composition in adolescents.
AB  - During adolescence, little is known about the relationship between leptin and
      metabolic hormones and how these are modified by body composition and exercise.
      This study determined: 1) the relationships between leptin, triiodothyronine,
      cortisol, and insulin, and 2) whether these relationships were modified by body
      composition and exercise. Fasting hormonal concentrations were assessed from 80
      girls and 80 boys, aged 11-18 yr. In a multiple regression model, including the
      hormones and gender, only gender and insulin were significant predictors of
      leptin (R2 = 0.394; p <0.001). In a second model, including body fat and
      exercise, the levels of body fat, gender, free triidothyronine and cortisol
      explained 59.6% of the variance in leptin (p <0.05). The results suggest that in
      adolescents, the relationship between leptin and insulin is mediated by body fat.
      Leptin is negatively associated with cortisol in boys and with thyroid hormones
      in girls; these hormones possibly interact to sustain normal growth and
      maturation.

PMID- 16459455
TI  - High prevalence of diabetic polyneuropathy in a group of Brazilian children with
      type 1 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the prevalence of diabetic polyneuropathy (DNP) in
      children and adolescents with type 1 diabetes mellitus (DM1), and to compare the
      diagnostic criteria for DNP proposed and most widely utilized in the literature.
      METHODS: Forty-eight patients with DM1 with a mean age of 12.9 years and mean
      duration of DM1 of 7 years, and 14 controls, were compared. Results of clinical
      neurological examination and nerve conduction (NC) were compared by means of
      diagnostic criteria proposed at the San Antonio Conference and by Dyck et al.
      RESULTS: Twenty-two patients (46%) had DNP by the San Antonio criteria, and 25%
      according to those of Dyck et al. Three patients (6.3%) presented neurological
      complaints, such as lower limb pain, paresthesia and hyperhidrosis, and 31
      (64.6%) presented peripheral nervous system changes upon clinical examination.
      Twenty-nine patients (60.4%) presented changes in motor and sensory nerve
      conduction. Motor NC changes were the most prevalent, above all in the median
      (86.2%) and fibular (55.2%) nerves. CONCLUSIONS: A high percentage of
      neurological changes were detected in this young population, with 5-10 years
      duration of DM1. Prevalence of DNP in the pediatric age group ranges from zero to
      54% in published studies, mainly using the criteria of Dyck et al. or similar
      criteria. In the present study we found that roughly one-quarter of patients
      would be misdiagnosed according to the criteria utilized. We propose that
      neurological evaluation must be included in routine care for children with DM.
      Further studies leading to a more accurate diagnosis of DNP in children and
      adolescents are still necessary.

PMID- 16459454
TI  - Preproghrelin Leu72Met polymorphism in obese Korean children.
AB  - Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and
      adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222
      obese Korean children to determine whether it is associated with obesity. The
      frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in
      overweight, and 32.5% in lean Korean children. No significant difference was
      found between Met72 carrier and non-carrier obese children with respect to BMI,
      total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol
      levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not
      associated with obesity in children.

PMID- 16459456
TI  - Neonatal diabetes mellitus: patient reports and review of current knowledge and
      clinical practice.
AB  - Neonatal diabetes mellitus (NDM) is a rare disease reported to have an incidence
      of one in 400,000 to 500,000 live births. The disorder may be more common as it
      is not routinely considered a diagnostic possibility by many neonatologists who
      may routinely use insulin to treat neonatal hyperglycemia. NDM can be grouped
      into two distinct clinical entities--transient and permanent--based on certain
      features detailed herein; however, distinction between the two categories can
      only be definitely made in hindsight. Treatment is with insulin; however,
      determining the correct dose and method of delivery is often challenging, given
      the sensitivity of neonates to insulin and the risk of hypoglycemia. We report
      the successful use of Glargine insulin in the treatment of three infants with
      NDM, review the recent discoveries, and discuss guidelines for the care of
      newborns with NDM.

PMID- 16459457
TI  - Persistent hyperinsulinaemic hypoglycaemia of infancy: 15 years' experience at
      the Royal Children's Hospital (RCH), Melbourne.
AB  - OBJECTIVE: To review the clinical outcome and report our experience of patients
      with persistent hyperinsulinemic hypoglycaemia of infancy (PHHI). METHODS:
      Retrospective case series of 14 patients diagnosed with PHHI at the Royal
      Children's Hospital in Melbourne in the period between 1988 and 2004. Diagnoses
      of insulinoma, Beckwith syndrome and transient hyperinsulinism were excluded.
      RESULTS: Six patients (43%) presented on day 1, with a median presenting age of
      2.75 months; ten (71.4%) presented with seizures. All were initially treated with
      diazoxide, of whom six (43%) recovered and are off medication, while four
      patients (28.5%) required surgery (twice in one patient). One developed permanent
      diabetes mellitus. Developmental delay occurred in nine (64%), and was severe in
      two (14.5%) patients, possibly associated with delayed treatment. CONCLUSIONS:
      PHHI is a rare but severe condition. The aim of management of PHHI should be on
      the one hand to prevent mental retardation and developmental delay due to severe
      and persistent hypoglycaemia, and on the other hand to avoid the induction of
      diabetes mellitus following surgery. Satisfactory outcome depends on early
      effective medical treatment and judicious use of surgery by an experienced
      operator.

PMID- 16459458
TI  - Depression, levels of anxiety and self-concept in girls with Turner's syndrome.
AB  - Self-esteem, depressive symptoms and anxiety symptoms in girls with Turner's
      syndrome (TS) were compared to those in girls with familial short stature (FSS)
      and healthy controls (NC). Eleven girls with TS, 9-17 years of age, all with
      45,X0 karyotype, who were matched with 11 girls with FSS and 11 NC girls who had
      similar socio-demographic characteristics, were enrolled in the study. The
      Children's Depression Inventory (CDI), State-Trait Anxiety Inventory for Children
      (STAIC), and Piers-Harris Children's Self Concept Scale (PHSCS) were used to
      assess the extent of depression, anxiety and self reported self-esteem. The PHSCS
      means and standard deviations of the TS, FSS and NC groups were 56.2 +/- 6.7,
      62.7 +/- 6.9, and 69.3 +/- 6.0, and the STAIC-state anxiety means and standard
      deviations were 30.6 +/- 4.5, 28.8 +/- 6.1, and 25.7 +/- 3.7, respectively. Study
      findings showed that girls with TS had lower self-esteem and higher state anxiety
      levels than NC (p <0.05). In spite of the small sample size, findings showed that
      girls with TS were at risk of psychological problems. Therefore, in addition to
      medical treatment and monitoring, girls with TS should also be supported
      psychologically by social, educational and psychotherapeutic interventions which
      aim to address their self-esteem and emotional difficulties.

PMID- 16459459
TI  - The CBLB gene and Graves' disease in children.
AB  - The CBLB gene functions as a negative regulator of autoimmunity. Impairment of
      the Cbl-b signaling pathway may contribute to human autoimmune disease. dbSNP
      rs2305035 is a C/T polymorphism located in exon 10 of the CBLB gene. We report an
      association study of this polymorphism in children with Graves' disease. The
      patients were 158 unrelated children (125 girls) with Graves' disease, aged 9.8
      +/- 3.3 years. The controls consisted of 237 adults without a history of
      autoimmune disease. The C allele and phenotype frequencies of patients and
      controls were 247 (78.2%) vs 356 (75.1%) (OR = 1.19, p >0.05) and 151 (95.6%) vs
      221 (93.2%) (OR = 1.56, p >0.05), respectively. The allelic polymorphism in
      patients and controls with and without DRB1*09012 were also not significantly
      different. This study demonstrates that the C/T polymorphism in exon 10 of the
      CBLB gene is not associated with Graves' disease in children.

PMID- 16459460
TI  - Prenatal Cushing's syndrome secondary to nodular adrenocortical hyperplasia with
      unsuppressed plasma ACTH levels.
AB  - We report a newborn girl (36th week of gestation, birth weight 1,054 g) with
      Cushing's syndrome secondary to nodular adrenocortical hyperplasia with normal
      plasma ACTH levels. From birth she was hypertensive, hyperglycaemic and slightly
      hirsuit. Hypercortisolaemia (>1,380 nmol/l) was accompanied by normal plasma ACTH
      levels (8.64-23.9 pg/ml). A 48-h dexamethasone suppression test decreased plasma
      cortisol by 35%, indicating some degree of ACTH dependency. However, there was no
      ACTH rise on CRF test. MRI showed enlarged adrenal glands with a possible cyst on
      the right; the pituitary gland was normal. At the age of 6 weeks she underwent
      bilateral adrenalectomy. Histology showed enlarged adrenals with multiple non
      pigmented nodules (up to 5 mm) in both glands. However, over the next few weeks
      she developed liver failure and sepsis. She died at the age of 3 months. Post
      mortem examination confirmed the diagnosis. Nodular adrenocortical hyperplasia
      may present at birth with severe Cushing's syndrome and unsuppressed ACTH levels,
      indicating some degree of ACTH dependency in this condition.

PMID- 16459461
TI  - Different outcomes of neonatal thyroid function after Graves' disease in
      pregnancy: patient reports and literature review.
AB  - Graves' disease in pregnancy is a rare condition that directly affects neonatal
      thyroid function. We describe three newborns born to mothers with Graves' disease
      and discuss differences in outcomes and management. The first infant presented
      with a goiter at birth but was euthyroid and did not require therapy. The second
      infant presented with thyroid storm and the third infant present with neonatal
      hyperthyroidism, and both required treatment with antithyroid drugs. There was
      documented elevation of maternal and infant thyroid stimulating hormone
      immunoglobulin (TSI) levels in all three infants. Management of an infant born to
      a mother with Graves' disease should include monitoring of both maternal and
      neonatal thyroid function, and maternal TSI levels during pregnancy. Treatment
      may be needed if the newborn is symptomatic. With clearance of maternal
      antibodies and antithyroid drugs, manifestations of abnormal thyroid function in
      the neonate gradually regress, including eventual resolution of a goiter, if
      initially present.

PMID- 16459462
TI  - Analysis of costimulatory molecules OX40/4-1BB (CD134/CD137) detection on chosen
      mononuclear cells in children and adolescents with Graves' disease during
      methimazole therapy.
AB  - Antibody synthesis follows interactions between the T cell receptor (TCR) on
      activated T lymphocytes and the main histocompatibility complex (MHC) present on
      APC cells, resulting in lymphocyte proliferation, as well as cytokine synthesis
      and release. The involvement of costimulatory markers OX40/4-1BB/4-1BBL leads to
      the enhancement of signals which are necessary for lymphocyte activation in
      addition to the antigen-specific signal and may prevent anergy. The aim of this
      study was to estimate the expression of OX40 and 4-1BB molecules on peripheral
      blood cells in patients with Graves' disease (GD) (n = 35, mean age 16.5 +/- 6.1
      years) and non-toxic nodular goiter (NTNG) (n = 35, mean age 16.2 +/- 4.7 years),
      in comparison with sex- and age-matched healthy controls (n = 35, mean age 16.2
      +/- 2.1 years). Expression of the costimulatory molecules on mononuclear cells
      was analyzed by three-color flow cytometry using a Coulter EPICS XL cytometer.
      Stimulating and blocking antibodies to the TSH-receptor using JPO9 CHO cells in
      unfractionated serum were measured by a highly sensitive commercial
      radioimmunoassay. The analysis of OX40/4-1BB expression in patients with newly
      recognized Graves' disease revealed a statistically significant increase in the
      percentage of CD134+ T cells (7% vs 1.4%, p <0.001) and CD137+ T cells (3.2% vs
      0.8%, p <0.04) compared to the control group. After 2-6 months of methimazole
      therapy, the percentage of these cells in the peripheral blood of hyperthyroid
      patients returned to normal values. In addition, the expression of 4-1BBL
      (CD137L) was detected only on the surface of active monocytes in patients with
      untreated GD (3.8%), while in the group with nodular goiter and controls the
      values were trace (0.6% and 0.2%, respectively). We conclude that the changes of
      expression of costimulatory molecules on the surface of peripheral blood T cells
      and their significant relationship with the level of antithyroid antibodies
      indicate an involvement of these molecules in the pathogenesis of Graves'
      disease. A marked increase in the percentage of CD134/ CD137+ T cells at disease
      onset may indicate the need for more aggressive therapy in Graves' disease and
      for a greater duration than the standard 3-year period.

PMID- 16459463
TI  - Global fibrinolytic capacity is decreased in girls with premature adrenarche: a
      new pathological finding?
AB  - OBJECTIVE: Global fibrinolytic capacity (GFC) is a sensitive method reflecting
      all of the molecular components involved in the process of fibrinolysis.
      Recently, a decrease in GFC has been shown in women with polycystic ovary
      syndrome (PCOS). Girls with premature adrenarche (PA) have been shown to have
      hyperinsulinemia and dyslipidemia in addition to hyperandrogenemia, similar to
      women with PCOS. The aim of this study was to evaluate GFC levels in girls with
      PA. PATIENTS AND METHODS: Twenty-five girls with PA, who had developed
      pubic/axillary hair at age of 7.09 +/- 0.74 (5.1-7.9) years, were studied at the
      age of 10.04 +/- 1.53 years and compared with 20 age-matched healthy controls and
      10 girls with PCOS (mean age 16.58 +/- 1.46 years). RESULTS: Median DHEAS and
      free testosterone levels were significantly higher in girls with PA than in the
      control group. The median serum sex hormone binding globulin (SHBG) level was
      higher in controls than in both PA and PCOS groups (49.85, 38.60 and 21.30
      nmol/l, respectively). The median fasting glucose:insulin ratio (FGIR) levels
      were similarly low in PA and PCOS groups, while it was significantly higher in
      controls. The FGIR levels were less than 7 in 52% of girls with PA and 50% of
      girls with PCOS; however, in controls, only 5% of girls had FGIR <7. Median GFC
      in girls with PA (1.67 microg/ml) and PCOS (1.06 microg/ml) were significantly
      lower than that of the controls (3.48 microg/ml, p <0.001). The GFC level
      correlated positively with SHBG and FGIR. CONCLUSION: A reduction in GFC was
      demonstrated in girls with PA compared to healthy controls. This important
      finding, newly added to previous ones, may strengthen the view that PA is not a
      benign condition, and also points to the presence of potential risk factors for
      vascular diseases in these girls starting from childhood.

PMID- 16459464
TI  - Diagnosis of 5alpha-reductase type 2 deficiency: contribution of anti-Mullerian
      hormone evaluation.
AB  - AIM: To evaluate anti-Mullerian hormone (AMH) levels in patients with clinical
      and molecular diagnosis of 5alpha-reductase 2 deficiency. PATIENTS AND METHODS:
      Data from 14 patients whose age ranged from 21 days to 29 years were analyzed
      according to age and pubertal stage. Sexual ambiguity was rated as Prader III in
      11 patients. LH, FSH, testosterone (T), dihydrotestosterone (DHT) and AMH serum
      levels were measured in all but two patients, who had been previously submitted
      to gonadectomy; T and DHT were also measured in 20 age-matched controls. RESULTS:
      Gonadotropin levels were normal in all but one patient who retained gonads (six
      of whom had reached puberty) and T/DHT ratio was elevated in all patients when
      compared to controls. All prepubertal patients had AMH levels < -1 SD for age,
      while most pubertal patients had AMH levels compatible with pubertal stage.
      CONCLUSIONS: Prepubertal patients with 5alpha-reductase 2 deficiency have AMH
      values in the lower part of the normal range. These data indicate that T does not
      need to be converted to DHT to inhibit AMH secretion by Sertoli cells.

PMID- 16459465
TI  - Clinical picture, evolution and peculiar molecular findings in a very large
      pedigree with Wolfram syndrome.
AB  - OBJECTIVES: a) To describe a very extended inbred pedigree with Wolfram syndrome
      (WS) (OMIM #222300); b) to report both the clinical picture and evolution in this
      large family and a peculiar mutation which has been reported hitherto only in
      Italian patients. DESIGN: The five-generation pedigree from Sicily was
      reconstructed through a proband with all the main manifestation of WS, born to a
      couple of healthy consanguineous parents. DNA examination was performed in both
      patients and healthy family members. RESULTS: In all seven patients we found a
      homozygous 16-bp deletion in exon 8 of the WFS1 gene that introduces a stop codon
      in position 454. CONCLUSIONS: This inbred pedigree is the largest with WS
      described in the literature. Its analysis definitively confirms the view of
      autosomal recessive inheritance in WS. The 16-bp deletion appears to be a
      relatively frequent mutation only in Italian patients. Before examining the
      entire coding region of the WSF1 gene a preliminary screening for the 16-bp
      deletion in exon 8 might be suggested when a new Italian case of WS is
      investigated.

PMID- 16459466
TI  - BMI-conditional standard of leptin serum values in children: proposal of a
      statistical procedure for the analysis of influencing variables.
AB  - In order to define serum leptin values in children, its concentration was assayed
      in 3,453 children, 5-14 years old, and body mass index (BMI) and pubertal
      development were recorded. Insulin, testosterone (in males) and 17beta-estradiol
      (in females), the sum of four skinfold thicknesses (SST), waist-to-hip ratio, and
      body fat mass were also determined in 1,601 children. Analysis of
      multicollinearity effects on estimated models demonstrated a quasi-linear
      correlation between SST and BMI, the former being prevalent. Although other
      variables were strongly correlated with leptin, assuming only SST as predictor,
      R2 yielded a value of 0.711 in males and 0.607 in females. When the other
      variables were added, R2 increased by about 0.03 in both sexes. BMI and SST were
      the most important of all the predictors and each can act as a sort of proxy for
      the others. When the z-scores of BMI of all 3,453 children were subdivided into
      deciles, any correlation with leptin was no more significant inside each BMI z
      score range. This study demonstrates that subcutaneous fat mass may be considered
      the prevalent determinant factor. The adopted statistical procedure furnished
      results useful for reference values based on BMI z-score as a simple and
      appropriate evaluation for serum leptin concentrations in children.

PMID- 16459467
TI  - Serum alpha-tocopherol concentrations and risk of type 1 diabetes mellitus: a
      cohort study in siblings of affected children.
AB  - Animal models have indicated that alpha-tocopherol may protect against type 1
      diabetes mellitus (DM1). Epidemiological data on the subject are scarce. The
      objective of this study was to evaluate the association of serum alpha-tocopherol
      concentration and risk of DM1 in a cohort of initially non-diabetic siblings of
      children affected by DM1 (n = 722). We used two study designs: 1) Siblings who
      progressed to DM1 were compared with control siblings who remained negative for
      DM1-associated autoantibodies in a nested case-control study design. 2) All
      siblings with DM1-associated autoantibodies were prospectively followed for DM1.
      In both designs, high concentrations of serum alpha-tocopherol tended to be
      associated with a lower risk of DM1 (p = 0.08 and 0.09, respectively). Although
      the results did not reach statistical significance, they support the hypothesis
      that high alpha-tocopherol levels may protect against DM1.

PMID- 16459468
TI  - Anti-CD38 autoimmunity in children with newly diagnosed type 1 diabetes mellitus.
AB  - AIMS: To test for anti-CD38 autoimmunity in children with newly-diagnosed type 1
      diabetes mellitus (DM1). METHODS: Serum anti-CD38 autoantibodies were detected by
      Western blot in 270 children (130 girls, 140 boys, mean age 8 +/- 4 years) with
      newly-diagnosed DM1 and 179 gender- and age-matched non-diabetic children. In 126
      diabetic children, another blood sample was obtained 15 +/- 4 months after the
      diagnosis. RESULTS: Anti-CD38 autoantibody titers at least 3 SD above the mean
      value for the control group were found in 4.4% of children with DM1 vs 0.6% of
      controls (chi2 = 5.8, p <0.016). No statistical differences were observed between
      anti-CD38 positive and negative patients in terms of phenotype. At follow-up, of
      six diabetic children who were positive for anti-CD38 antibodies, two were new
      cases. A positive correlation was found between the antibody titer of diabetic
      sera at diagnosis and follow up (r = 0.46, p <0.0001). CONCLUSION: An autoimmune
      reaction against CD38, a protein expressed in human islets, is associated with
      newly-diagnosed DM1. In children with DM1, CD38 autoimmunity increases with time
      and persists.

PMID- 16459470
TI  - Ghrelin, IGF-I and IGFBP-3 levels in children with type 1 diabetes mellitus.
AB  - There is a strong relationship between ghrelin, insulin, glucose and IGF-I/IGFBP
      3 metabolism. This aim of this study was to investigate ghrelin level, and its
      relationship with IGF-I and IGFBP-3 levels in children with type 1 diabetes
      mellitus (DM1). Twenty-seven children with DM1 and 25 healthy controls were
      investigated. Ghrelin levels were similar, and IGF-I and IGFBP-3 levels were
      lower, in prepubertal and pubertal patients compared to controls. In the patient
      group, ghrelin levels were negatively correlated with chronological age, height,
      weight, pubertal status and IGF-I, but had no correlation with fasting glucose,
      HbA1c, insulin dose, duration of insulin therapy, and IGFBP-3 levels. Similar
      ghrelin levels in patients compared to controls may suggest that ghrelin levels
      remain unchanged in children with DM1, or that altered ghrelin levels at
      diagnosis recover as a consequence of insulin therapy. The lack of correlation of
      serum ghrelin levels with fasting plasma glucose, HbA1c and insulin dose suggests
      that ghrelin level is not affected by these parameters. Decreased IGF-I level and
      its negative correlation with ghrelin are compatible with previous findings.

PMID- 16459469
TI  - The role of diabetes duration, pubertal development and metabolic control in
      growth in children with type 1 diabetes mellitus.
AB  - OBJECTIVE: To investigate whether pubertal development, duration of type 1
      diabetes mellitus (DM1), or metabolic control play some role in the anomalies in
      growth observed in diabetic children. PATIENTS: We conducted a prospective
      evaluation of 83 patients (37 female, 46 male) who were followed from the onset
      of DM1 at the prepubertal stage until they reached final height. All patients
      were treated with a conventional regimen of insulin. METHODS: Height SDS, weight
      SDS, BMI SDS, duration of DM1 in years, and values of HbA1c were the study
      variables. RESULTS: In prepubertal (P1) girls (data for the initial vs the
      intermediate evaluations): weight SDS was -0.14 +/- 0.19 vs 0.11 +/- 0.20, p =
      ns; BMI SDS -0.25 +/- 0.15 vs 0.01 +/- 0.13, p = ns. In postpubertal (P3) girls,
      weight SDS was 0.49 +/- 0.2 vs 1.2 +/- 0.32, p <0.01; BMI SDS 0.09 +/- 0.16 vs
      1.03 +/- 0.24, p <0.01, whereas in P1 boys, height SDS was 0.16 +/- 0.30 vs -0.20
      +/- 0.27, p <0.05; and in P3 boys: 0.09 +/- 0.21 vs -0.28 +/- 0.26, p <0.05. Thus
      pubertal development influenced changes observed in girls with DM1, but did not
      do so in boys. The anomalies described in children with DM1 were observed from
      the third year of DM1 duration in both girls and boys. We did not observe any
      correlation between HbA1c values with height SDS, weight SDS or BMI SDS.
      CONCLUSIONS: The anomalies in growth observed in girls with DM1 are related to
      pubertal development, but this is not the case in boys. Alterations in children
      with DM1 were found from the third year of DM1 duration. Furthermore, the present
      data also indicate that the degree of metabolic control observed in our patients
      treated with modern but conventional regimen did not play a major role in the
      anomalies observed.

PMID- 16459471
TI  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI): Long-term outcome
      following 95% pancreatectomy.
AB  - OBJECTIVE: To evaluate the outcome of neonates and infants with persistent
      hyperinsulinemic hypoglycemia of infancy (PHHI) who had undergone 95%
      pancreatectomy, with special emphasis on development of diabetes mellitus (DM).
      METHODS: Ten infants diagnosed according to the established criteria of PHHI, and
      who had undergone 95% pancreatectomy, were followed for a period ranging from 1
      20 years (mean 13(4/12) years). A retrospective analysis of their data was
      carried out with special emphasis on growth and development, glycemic control,
      neurological status and school performance. The data on weight, glycemic control
      and daily insulin requirement were compared with a control group of ten children
      with type 1 DM (DM1), matched for age and sex. RESULTS: All ten children
      ultimately developed DM; three of them immediately following pancreatectomy and
      the remainder after a variable period ranging from 7(1/4)-11(1/2) years (mean:
      8(11/12) years). Data on their weight, HbA1c levels and daily insulin
      requirements when compared to ten children with DM1 showed no statistically
      significant difference in these biological variables. All the children, with the
      exception of one who sustained subarachnoid hemorrhage, cerebral edema and
      seizures in the neonatal period, were neurologically and developmentally normal.
      None exhibited clinical manifestations of pancreatic exocrine deficiency.
      CONCLUSION: 95% pancreatectomy is an effective treatment modality in PHHI not
      responding to medical treatment. In our experience; recurrence of hypoglycemia
      following surgery is uncommon and responds well to medical treatment. There is a
      high risk of secondary DM in these children; however, the serious risk of brain
      damage and neurological abnormalities could be avoided by early surgical
      intervention. Children in this study did not show any signs or symptoms of
      malabsorption.

PMID- 16459472
TI  - Elevated percentage of L-selectin on peripheral blood T lymphocytes (PBTLs) in
      children and adolescents with type 1 diabetes mellitus and vascular
      complications.

PMID- 16459474
TI  - In nursing, "mandatory" is not always bad.

PMID- 16459475
TI  - Democrats unveil womens health platform.

PMID- 16459476
TI  - The positive prognostic implications of crying during exam on threshold ROP.
AB  - INTRODUCTION: Most infants cry with lid speculum, scleral depression and indirect
      ophthalmoscopy. This simple observation, "did the infant cry?" during the initial
      31-week ROP screening exam was prospectively studied. METHODS: From Fall 1989
      through Summer 2003, all Alaskan infants with birthweight < or = 1500 grams were
      examined by RWA. After 1992, at the 31-week initial ROP screening, we recorded
      whether the infant was able to cry (cry), did not cry (quiet), or was intubated
      (vent) during indirect ophthalmoscopy with lid speculum and scleral depression.
      RESULTS: ROP was classified as to threshold in 873 infants. Infants who were able
      to cry during their 31-week GA screening exam were less likely to progress to
      threshold (Chi square 600, 2 = 36, p < .001). Using a logistic fit of Threshold,
      the increased risk of ROP in infants unable to cry persisted independent of
      gestational age or birthweight. CONCLUSIONS: Respiratory and neurologic co
      morbidity may render those infants unable to cry during the first screening
      examination at increased risk to progress to threshold ROP.

PMID- 16459477
TI  - Hounsfield unit density accurately predicts ESWL success.
AB  - Extracorporeal shockwave lithotripsy (ESWL) is a commonly used non-invasive
      treatment for urolithiasis. Helical CT scans provide much better and detailed
      imaging of the patient with urolithiasis including the ability to measure density
      of urinary stones. In this study we tested the hypothesis that density of urinary
      calculi as measured by CT can predict successful ESWL treatment. 198 patients
      were treated at Alaska Urological Associates with ESWL between January 2002 and
      April 2004. Of these 101 met study inclusion with accessible CT scans and stones
      ranging from 5-15 mm. Follow-up imaging demonstrated stone freedom in 74.2%. The
      overall mean Houndsfield density value for stone-free compared to residual stone
      groups were significantly different ( 93.61 vs 122.80 p < 0.0001). We determined
      by receiver operator curve (ROC) that HDV of 93 or less carries a 90% or better
      chance of stone freedom following ESWL for upper tract calculi between 5-15mm.

PMID- 16459478
TI  - From out of the past ... 30 years ago.

PMID- 16459480
TI  - Determination of citalopram in tablets by capillary zone electrophoresis and by
      direct and derivative UV-spectrophotometry.
AB  - Three rapid, simple and accurate analytical methods for the determination of
      citalopram in tablets were developed. The capillary zone electrophoresis (CZE)
      method was carried out using fused silica capillary with 67 mM phosphate buffer
      pH 7.0 as the background electrolyte, 30 kV of separation voltage and UV
      detection at 239 nm. The direct spectrophotometric method was performed by
      measuring the absorbance at the wavelength of 239 nm and derivative
      spectrophotometric assay was carried out by measuring the value of the second
      derivative of the spectrum at 210 nm. The linearity range for CZE method was 5-50
      microg/mL and for both spectrophotometric methods was 2-12 microg/mL. The
      recovery in CZE was between 98.6 and 102.4%, in the direct spectrophotometry
      between 95.0 and 98.0% and in derivative spectrophotometry between 97.6 and
      103.3%. The RSD values were between 1.36 and 2.30%, 1.80 and 2.70%, 1.52 and
      2.68%, respectively.

PMID- 16459481
TI  - Stability of 2-thiophenobarbital and its N-methyl derivatives in the presence of
      beta-cyclodextrin.
AB  - The rates of hydrolysis of thiophenobarbital and its N-mono- and N,N'-dimethyl
      derivatives were determined under different conditions of pH and temperature
      using UV spectroscopy. They were compared with those obtained in the presence of
      different concentrations of beta-cyclodextrin. It was found that the compounds
      degrade with different rates and beta-cyclodextrin retards the hydrolysis. The
      formation of complexes between the investigated compounds and beta-cyclodextrin
      was proved by 13C NMR and ROESY spectra and molecular modeling. The inclusion
      with the phenyl substituent into the beta-cyclodextrin cavity is preferred.

PMID- 16459482
TI  - Antimicrobial preservative effectiveness of natural peptide antibiotics.
AB  - The constantly growing resistance of microbes to drugs and other substances which
      fight microbial infections leads to search for new antimicrobial substances.
      Among substances which attract the scientists attention are antimicrobial
      peptides. Such compounds are quite common in nature and belong to the most
      important elements of the innate immune system of all living organisms. Numerous
      antimicrobial peptides have been isolated from insects, amphibians, mammals,
      plants and bacterial species. In this study we investigated the in vitro activity
      of two animal peptides, citropin 1.1 and protegrin 1 alone and in combination
      against microbial strains proposed for the evaluation of preservatives:
      Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, Pseudomonas
      aeruginosa ATCC 9027, Candida albicans ATCC 10231, and Aspergillus niger ATCC
      16404. The results of the antimicrobial preservative effectiveness were compared
      to the values received for benzalkonium chloride, popular preservative of
      medicines and cosmetics.

PMID- 16459483
TI  - Preliminary evaluation of anticonvulsant activity of some aroxyacetamides and
      aroxyethylamines.
AB  - A series of aroxyacetamides and aroxyethylamines were prepared and evaluated for
      anticonvulsant activity in the maximal electroshock seizure (MES) and
      subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for
      neurotoxicity (TOX). Most of them exhibited anticonvulsant activity in the MES
      screen (mice, i.p.) in the doses up to 300 mg/kg b.w. The most active compound
      was XVI, which given in the dose 100 mg/kg b.w. produced 100% anticonvulsant
      protection after 0.5 h without neurotoxicity. The most promising compound in the
      VIa phase (rats, p.o.) was VIII, which produced higher anticonvulsant protection
      (to 75% at 0.5 h).

PMID- 16459485
TI  - Enicostemma littorale Blume aqueous extract improves the antioxidant status in
      alloxan-induced diabetic rat tissues.
AB  - This study investigates the effect of oral administration of an aqueous
      Enicostemma littorale whole plant extract on antioxidant defense in alloxan
      induced diabetes in rats. A significant increase in blood glucose and increased
      concentration of thiobarbituric acid reactive substances (TBARS) and
      hydroperoxides (HP) in liver, kidney and pancreas were observed in alloxan
      diabetic rats. Decreased concentration of reduced glutathione (GSH) and decreased
      activities of superoxide dismutase (SOD), catalase and glutathione peroxidase
      (GPx) were also observed in these tissues of diabetic rats. Oral administration
      of aqueous E. littorale whole plant extract (1 and 2 g/kg) to diabetic rats daily
      for 45 days significantly decreased blood glucose, TBARS, HP and increased GSH,
      SOD, catalase and GPx. E. littorale extract at the dose of 2 g/kg was more
      effective than 1 g/kg. Insulin (6 units/kg) administration to diabetic rats for
      45 days brought back all the parameters to near normal status.

PMID- 16459484
TI  - CNS activities of Celesia coromandeliane Vahl. in mice.
AB  - The dried extracts of aerial parts of Celesia coromandeliane Vahl.
      (Scrophulariaceae) were evaluated for CNS activities in mice. The methanol
      extract of aerial part of Celesia coromandeliane (MECC) was found to cause
      significant depression in general as well as exploratory behavioral profiles in
      mice. MECC showed reduction in muscle relaxant activity by 30 degrees inclined
      screen test, as well as potential remarkably the pentobarbitone sodium-, diazepam
      and meprobamate-induced sleeping time of mice. The petroleum ether extract of
      aerial parts of Celesia coromandeliane (PECC) showed significant analgesic
      properties as evidenced by the significant reduction in the number of writhes and
      stretches induced in mice by 1.2% acetic acid solution. Pretreatment with PECC
      caused significant protection against strychnine- and leptazol-induced
      convulsions. All these results were compared with respective controls for the
      evaluation of significance. The presence of steroids in PECC and saponins in MECC
      might be responsible for respective CNS activities in mice.

PMID- 16459486
TI  - Effect of various formulation variables on the encapsulation and stability of
      dibucaine base in multilamellar vesicles.
AB  - Formulation of local anesthetics in liposomal topical drug delivery system could
      provide a sustained and localized anesthesia. The aim of this study was to
      develop a liposomal dibucaine base (DB) local anesthetic delivery system. DB
      loaded multilamellar vesicles (MLVs) were prepared through varying lipid
      composition, induced charge and pH of the hydration medium. Liposomes were
      characterized for morphology, size, entrapment efficiency (EE), in vitro drug
      release and stability including leakage stability. The percentage of drug
      entrapped in liposomes was found to be hydration medium pH dependent and charge
      dependent and more pronounced for negatively charged liposomes prepared using
      hydration medium of pH 9. In vitro release studies of liposomes have shown a
      sustained release of entrapped dibucaine compared to control solution. Results
      revealed that adjusting the various formulation variables of dibucaine base MLVs
      could yield stable and effective topical liposomal local anesthetic formulations.

PMID- 16459487
TI  - Release stability of 5-fluorouracil liposomal concentrates, gels and lyophilized
      powder.
AB  - Possible leakage of 5-fluorouracil from stable plurilamellar vesicles was
      monitored during storage of the liposomal concentrates, gels and lyophilized
      powders. Changes in release profile of dibucaine were taken as indicator of
      instability. Release profiles were obtained using the dialysis technique for a
      freshly prepared liposomal concentrate, gel or reconstituted lyophilized powder
      (zero time) and storage for one, two and four weeks in well closed tubes at 4
      degrees C for the liposomal concentrate or gel and at 25 degrees C for liposomal
      lyophilized powder. Aiming at increasing stability of 5-fluorouracil liposomal
      dispersion, freshly prepared liposomal concentrates were directly incorporated in
      hydroxypropyl methylcellulose gel. Stability release profiles of liposomal gels
      and concentrates indicated a significant increase in stability of liposomal
      formulations. Also, lyophilization increases the shelf life of liposomes by
      preserving it in a dry form as a lyophilized cake to be reconstituted immediately
      prior to administration or direct incorporation into a final dosage form. Release
      and physico-chemical stability studies showed superior potentials of the
      lyophilized product after reconstitution in comparison to concentrate and gel
      forms. It could be concluded that lyophilization of liposomes loaded with a water
      soluble drug such as 5-fluorouracil could significantly increase the stability of
      the liposomal vesicles and decrease leakage from it.

PMID- 16459488
TI  - Distribution of 125I-labeled [2-8]-leucopyrokinin, active analog of
      leucopyrokinin in rats.
AB  - The brain and internal organs distribution of 125I-labeled [2-8]-leucopyrokinin
      ([2-8]-LPK), a truncated analog of leucopyrokinin (LPK), an insect myotropic
      peptide injected into the lateral brain ventricle was determined in rats. A high
      accumulation of this analog in adrenals and in the hypothalamus and hippocampus
      of the brain was found. A lesser but significant [2-8]-LPK accumulation in other
      internal organs and parts of the brain was also observed. The results of the
      present study confirm results of our previous study performed on the distribution
      of labeled native LPK in rats. A possible significance of obtained results for
      the brain function was discussed.

PMID- 16459489
TI  - The influence of ambroxol and capsaicin on the isolated rabbit bladder wall.
AB  - Unmyelinated C-fibers endings lye beneath the epithelial layer and release
      neuropeptides which regulate baseline transepithelial potential difference (PD)
      and changes of transepithelial potential difference during mechanical stimulation
      (dPD). Ambroxol can suppress reflexes such as the cough or the corneal reflex
      which are connected to stimulation of C fibre endings. The study aimed to
      estimate the influence of ambroxol (ABX) and capsaicin (CAPSA) on PD and dPD in
      isolated rabbit bladder. The experiments were carried out on 26 bladder specimens
      of. 2 cm2 surface area each, obtained from 13 rabbits. Ussing apparatus was used.
      Procedure used for stimulation of sensory receptor involved directing stream onto
      epithelium. A stimulus lasted 30s, ejecting the 2.5 ml fluid. Amiloride and
      bumetanide were used to estimate of ionic currents. Each significant reaction was
      repeated at least 10 times on various specimens. PD ranged between 5 and 10 mV in
      different experimental conditions. Mechanical stimulation of isolated bladder
      wall caused increasing dPD about 2 mV defined as hyperpolarization. Application
      of ABX to the stimulation fluid decreased the hyperpolarization in comparison
      with control stimulation under conditions of inhibited chloride ion transport.
      Application of CAPSA to the stimulation fluid decreased the hyperpolarization in
      comparison with control stimulation under conditions of inhibited sodium ion
      transport. ABX and CAPSA had no influence on PD after mechanical stimulation. ABX
      as well as CAPSA influence on transepithelial ion transport pathways in bladder
      epithelium is dependent on sensory stimulation. ABX can be suspected to suppress
      bladder contractions.

PMID- 16459490
TI  - Piracetam--an old drug with novel properties?
AB  - Piracetam (2-oxo-1-pyrrolidine-acetamide), the most common of the nootropic
      drugs, is a cyclic derivative of gamma-aminobutyric acid. The treatment with
      piracetam improves learning, memory, brain metabolism, and capacity. Piracetam
      has been shown to alter the physical properties of the plasma membrane by
      increasing its fluidity and by protecting the cell against hypoxia. It increases
      red cell deformability and normalizes aggregation of hyperactive platelets.
      Piracetam is an agent with antithrombotic, neuroprotective and rheological
      properties. The interaction of this molecule with the membrane phospholipids
      restores membrane fluidity and could explain the efficacy of piracetam in various
      disorders ranging from dementia and vertigo to myoclonus and stroke.

PMID- 16459491
TI  - Synthesis and preliminary in vitro evaluation of 5'-O-esters of 2'-deoxyadenosine
      and 2-chloro-2'-deoxyadenosine with alpha-lipoic acid as potential prodrugs.

PMID- 16459492
TI  - Surveillance colonoscopy in patients with colorectal cancer: how often should we
      be doing it?
AB  - BACKGROUND: The optimum protocol for colonoscopic surveillance following curative
      resection for colorectal cancer has not been established. The aim was to assess
      the incidence of recurrence and metachronous tumours in our less intensive
      colonoscopic surveillance programme and compare our results with those reported
      from intensive surveillance programmes. METHODS: Colonoscopic records of patients
      who had surveillance colonoscopy following curative resection from April 1998 to
      March 2003 for cancer were available from the endoscopy department computer
      database. The variables studied included the tumour site, Duke's stage, number of
      recurrences, number of metachronous tumours, size and number of polyps and their
      biopsy results. RESULTS: There were a total of 105 patients. Two patients were
      diagnosed with metachronous tumours and three with recurrence. Adenomatous polyps
      were identified in 24 patients of which nine had multiple/advanced adenomas
      (equal to or more than 1cm adenomatous polyps, or with severe dysplasia).
      CONCLUSION: The risk of development of colonic pathology following curative
      resection for colorectal cancer is low. More intensive follow-up should be
      reserved for patients with additional risk of developing further cancers.

PMID- 16459493
TI  - Outcome of treatment of primary and recurrent pilonidal sinuses with the Limberg
      flap.
AB  - BACKGROUND: Surgical treatment of pilonidal sinus disease has a significant
      morbidity and recurrence rate. The rhomboid flap of Limberg is a transposition
      flap that has been advocated for treatment of this condition. We present our
      experience with the Limberg technique for both primary and recurrent pilonidal
      sinuses. PATIENTS AND METHODS: In a three-year period, 25 patients with chronic
      pilonidal sinus disease were treated with this method. Twelve patients had
      recurrent disease and were previously treated with other types of surgery. The
      sinuses were excised in a rhomboid fashion and the defect closed using a
      transposition flap designed to obliterate the midline cleft. Patients were
      treated with prophylactic antibiotics and the wound drained with a vacuum drain.
      RESULTS: Median post-operative hospital stay was four days. There were four (16%)
      wound complications. The mean follow-up period was 20 months. There was a single
      recurrence (4%) of a pilonidal sinus, which required further surgical excision.
      CONCLUSIONS: Despite the risk of wound complications, this method is particularly
      useful for complex sinuses with extended tracts where radical excision leaves a
      large defect. It is also suitable for cases where simpler operations have failed
      and carries a low risk for recurrence.

PMID- 16459494
TI  - Audit of nasendoscope disinfection practice.
AB  - INTRODUCTION: Several options exist with regard to flexible pharyngo-laryngoscope
      sterilisation. We audited the use of disposable sheaths in our department over a
      six-month period. METHODS: A cost-analysis was performed and the advantages and
      disadvantages of this system were compared with several alternative options.
      RESULTS: We found that the overall cost of disposable sheaths averaged l4008 per
      month over a six-month period. We subsequently introduced chlorine dioxide (ClO2)
      wipes as a means of disinfection. Chlorine dioxide wipes have enabled a monthly
      saving of l3145 over sheath usage. Additionally, they meet health regulation
      requirements and are a convenient, cost-effective alternative to sheaths.
      DISCUSSION: The limiting factors, including time and financial issues, involved
      in nasendoscope disinfection are discussed. CONCLUSIONS: We have found chlorine
      dioxide wipes to be a satisfactory alternative means of nasendoscope
      disinfection. Possible time constraints aside, there are no advantages of sheath
      use over our current method. Chlorine dioxide wipes are also preferable from a
      financial point of view.

PMID- 16459495
TI  - Women presenting with lower abdominal pain: a missed opportunity for chlamydia
      screening?
AB  - INTRODUCTION: Many young women presenting with lower abdominal pain are referred
      to general surgeons with possible appendicitis. For some of these patients there
      will be a gynaecological cause for their pain. There has been a steady increase
      in the incidence of Chlamydia infections and pelvic inflammatory disease (PID)
      among the general population. Therefore, are general surgeons considering this as
      a diagnosis for lower abdominal pain in women? METHODS: One hundred and ninety
      three women who had been admitted with lower abdominal pain to a single hospital
      between 1999 and 2001 were identified using computerised records and the notes
      were examined. One hundred and eighty six women were included in the audit.
      Investigations and treatments instigated for these patients were then carefully
      recorded. RESULTS: Seventy-four patients underwent appendicectomy, of which 59
      were histologically confirmed. Eighty-nine patients (47.8%) of admissions had no
      final diagnosis and were not screened for Chlamydia trachomatis. Sexual history
      was recorded in only 51% of admissions. Vaginal swabs were sent in only 7.3% of
      admissions. CONCLUSION: Current guidelines for Chlamydia trachomatis screening
      produced by the Chief Medical Officer (CMO) include screening in women presenting
      with lower abdominal pain as well as those with post-coital or intermenstrual
      bleeding. Most women who present with classical symptoms of PID will present to
      gynaecological specialities for further management. However, a significant number
      of women presenting atypically will be referred to surgeons to exclude
      gastrointestinal causes for their lower abdominal pain. These women could and
      probably should be screened for Chlamydia trachomatis.

PMID- 16459496
TI  - Axial fixation of testes for prevention of recurrent testicular torsion.
AB  - Testicular torsion is a surgical emergency that requires prompt exploration in
      order to maintain testicular viability. All testicular fixation techniques, so
      far in use, are not entirely reliable in preventing recurrences. Although
      recurrent testicular torsion after previous fixation is rare, in cases that it
      occurs, it is associated with atrophy of the testis or gangrene leading to loss
      of the testes. The most common cause for recurrence is improper or inadequate
      fixation. We describe a simple and effective method using a four point fixation,
      which is likely to prevent testicular torsion recurrences.

PMID- 16459497
TI  - The immunological consequences of injury.
AB  - Immediate and early trauma death rates are determined by "first hits" such as
      hypoxia, hypotension and organ injury, while late mortality correlates closely
      with "second hits" such as infection. An imbalance between the early systemic
      inflammatory response (SIRS), and the later compensatory counter-inflammatory
      response (CARS), is considered to be responsible for much post-traumatic
      morbidity and mortality. From a clinical perspective, this remains a significant
      healthcare problem, which has stimulated decades of experimental and clinical
      research aimed at understanding the functional effects of injury on the immune
      system. This review describes the impact of injury on the innate and adaptive
      immune systems. Though it is worth noting that the features of the immune
      response to injury overlap in many areas with immune dysregulation in sepsis, we
      attempt here to elucidate the mechanism by which injury predisposes to infection
      rather than to describe the alterations in host immunity consequent to
      established sepsis.

PMID- 16459498
TI  - Laparoscopic geometrical repair of ventral hernia.
AB  - BACKGROUND: Recurrence after ventral hernia repair is a common problem worldwide.
      Laparoscopic mesh repair has been associated with fewer recurrences and also
      minimal morbidity. The technique of the laparoscopic repair is based on the
      principle described by Stoppa, however the hernial sac is not dissected and is
      left behind. This minimizes difficult dissection, blood loss and large incisions.
      The mesh in laparoscopic repair is fixed intraperitoneally using tackers or with
      the dual method of tackers and sutures, but some kind of suture fixation is
      mandatory. We describe a technique of fixing the mesh with sutures only. METHOD
      AND RESULTS: Over a period of 52 months 88 ventral hernias were repaired using
      the suture only technique. The mean size of the defect was 9.0cm (65.0cm2) and
      the mean size of mesh used was 19.5cm (293.5cm2). Our technique involves fixing
      the mesh with sutures circumferentially in two circles. The tackers and staplers
      were not used. The sutures are placed at fixed intervals, in fixed numbers and in
      fixed positions as mapped out with the help of circular protractors, compass and
      ruler. The protractors helped us in standardizing the placement intervals of
      sutures and in the orientation of the mesh. The orientation is maintained even
      for a very large mesh. There was no infection of the mesh, recurrence or
      mortality. The patient experienced minimal wound pain and the recovery was
      quicker. CONCLUSION: This is the only technique of laparoscopic ventral hernia
      repair we are aware of in which the suture intervals, position of the sutures and
      the number of sutures are standardized. This approach is suitable for all types
      of ventral hernia. It is safe, cost-effective and, so far, recurrence free.

PMID- 16459499
TI  - Re-engineering Colles: form, function and fragility fractures.
AB  - Of the twenty nine anatomy professors in the Royal College of Surgeons in
      Ireland, primus inter pares is Abraham Colles. In his 1811 book A Treatise on
      Surgical Anatomy he revolutionised the subject by teaching it topographically,
      seeking "to describe the relative position of the parts and to point out the
      subservience of anatomical knowledge to surgical practice". Today we have
      extended this to 'clinical practice' and, in the Anatomy Room, students are
      guided through each region by clinically trained staff, from surface anatomy via
      three-dimensional dissection to radiological images. This is augmented by online
      histology and radiology courses and DVDs in which dissection footage, edited by a
      content analysis engine, is used to preview and review practical classes. In the
      same book, Colles also wrote that 'the fixed and immutable laws of mathematics
      are little applicable to the science of medicine'. Computer-aided learning argues
      against this. So does research which links fatigue microdamage to bone
      remodelling and the development of algorithms to predict, and thus prevent,
      osteoporotic fractures. Mechanical principles are being used to develop scaffolds
      for tissue engineering and to optimise the mechanical environment of seeded
      mesenchymal stem cells. While Colles' teaching approach holds true, in
      biomechanics, tissue engineering and computing, mathematical laws are now being
      successfully applied to medical science.

PMID- 16459500
TI  - Wegener's granulomatosis: a rare, chronic and multisystem disease.
AB  - Wegener's granulomatosis (WG) is an autoimmune disease which has a clinical
      predilection for the upper airways, lungs and kidneys. It is a necrotising
      granulomatous vasculitis which is associated with a distinct autoantibody--the
      antineutrophil cytoplasmic antibody (ANCA). A heightened index of suspicion by
      clinicians is needed in the diagnosis of this complex and rare condition. A
      multidisciplinary approach should then be used to treat this chronic multisystem
      disease. Treatment involves the use of various regimens of corticosteroids and
      immunosuppressive medication. Mortality due to WG has been significantly
      decreased by this therapy. In this article, we focus on clinical manifestations
      and review the salient histologic, laboratory and serologic features and
      treatment.

PMID- 16459501
TI  - Post-caesarean incisional hernia or scar endometrioma?
AB  - Scar endometrioma is an uncommon condition following caesarean section. It
      presents as a lump on the caesarean scar and can often be painful. Endometrioma
      is referred to the general surgeon as an incisional hernia. We present six such
      patients referred to the general surgical department by either the general
      practitioner or the gynaecologist. Scar endometrioma is believed to arise due to
      implantation of endometrial tissue during caesarean section. Cyclical pain, as in
      endometriosis, is characteristic but uncommon. Local wide excision remains the
      treatment of choice.

PMID- 16459502
TI  - Cutaneous mycobacterial infection post intravesical BCG installation.
AB  - Disseminated tuberculous lesions post intravesical BCG therapy are rare but need
      to be identified and treated quickly. We report the first case of a tuberculous
      cutaneous lesion in a patient receiving the above treatment.

PMID- 16459503
TI  - Anatomy teaching.

PMID- 16459504
TI  - Re: Power et al. Needle-localised biopsy of impalpable breast lesions: a novel
      adjunct to surgical technique and specimen mammography. Surg J R Coll Surg Edinb
      Irel 2004; 2(6): 343-45.

PMID- 16459505
TI  - Re: AC Anyanwu, SM Moalypour. Are abdominal radiographs still overutilised in the
      assessment of acute abdominal pain? A district general hospital audit. J R Coll
      Surg Edinb Irel 1998;43(4): 267-70.

PMID- 16459506
TI  - Re: Golash V. Technique of suturing the mesh in laparoscopic total extra
      peritoneal (TEP) repair of inguinal hernia. Surgeon 2004; 5: 264-72.

PMID- 16459507
TI  - Developments with regard to end-of-life decisions in newborns.

PMID- 16459508
TI  - Human immunodeficiency virus type-1 (HIV-1) subtypes in Jamaica.
AB  - The subtypes of 141 isolates of human immunodeficiency virus type-1 (HIV-1) from
      Jamaica were determined by a combination of env and gag heteroduplex mobility
      analysis (HMA) genotyping. The majority of HIV-1 isolates were subtype B
      (131/141, 93.0%); one (0.8%) isolate each of subtypes C, D and E was found and 7
      (4.9%) were indeterminate. These results and the failure of the sets of primers
      used to amplify some of the HIV-1 isolates provide strong evidence of genetic
      diversity of the HIV/AIDS epidemic in Jamaica. Surveillance of the circulating
      HIV-1 genetic subtypes is a pre-requisite for developing regional vaccine
      strategies and understanding the transmission patterns of the virus. This is the
      first study of its kind in Jamaica and the findings complement data from other
      Caribbean countries. This work supports the view of colleagues from the French
      and Spanish-speaking Caribbean that an epidemiological network supported by
      regional laboratories will help track this epidemic accurately with positive
      outcomes for the public.

PMID- 16459509
TI  - Field trial to test and evaluate primary tobacco prevention methods in clusters
      of elementary schools in Barbados.
AB  - To evaluate methods of preventing young children from experimenting with tobacco
      and to determine cost effectiveness, students (n = 1005) in 31 primary schools,
      from randomly selected higher grade-levels were recruited into a partially
      randomized, single blinded controlled trial in which seven groups of schools were
      randomly assigned to a combination of teaching, leaflet, and drama, in order to
      modify students' knowledge, attitudes, beliefs and behaviour (KAB). The eighth
      group (n = 346) with ten schools, distantly separated from the former, was
      assigned to be the control, but was dropped from comparison analysis for lack of
      randomness at baseline. The mean, standard deviation and median age of the
      intervention groups was 9.94 years (0.81), 10.0 years, (n = 669) at baseline; and
      10.62 years (0.66), 11.0 years, (n = 397), at 12 months follow-up. In all, 6.6%
      had ever used tobacco at least once at a median age of seven years. Teaching
      health education at school when combined with other methods was significantly
      better at improving KAB. In 2003, after a year post-intervention, the occurrence
      of experimentation smoking in the last 30 days, dropped from 9.2% to 1.2% (p =
      0.00), equivalent to 87% (95% CI 78, 93) reduction in the group exposed to health
      education compared to none in the leaflet-only group and Numbers Needed to Treat
      (NNT) = 12.5. Due to its cost-effectiveness (comparable to child immunizations)
      at BDS dollars 1.89 to 2.89 or US dollars 1 to 1.5 per child contacted and BDS
      dollars 100 to 140 (US dollars 50 to 70) capital investment in other resources
      per school, the experience could be utilized routinely in elementary schools.

PMID- 16459510
TI  - Iron deficiency anaemia in Jamaican children, aged 1-5 years, with sickle cell
      disease.
AB  - OBJECTIVE: The aim of this study was to determine, using a combination of
      measures, the prevalence of iron deficiency anaemia (IDA) in children under five
      years-of-age who have sickle cell disease (SCD) and attend the Sickle Cell Clinic
      (SCU) of the Tropical Medicine Research Institute. MATERIALS AND METHODS:
      Children with homozygous sickle cell anaemia (Hb SS) or doubly heterozygous for
      Hb S and Hb C (Hb SC) disease who had not received a blood transfusion within
      three months prior to the iron measurements, were enrolled. The diagnosis of IDA
      was made if transferrin saturation was less than 16% with serum iron less than
      10.7 micromol/l and a low mean corpuscular volume (MCV) for age. RESULTS: Twelve
      children (8.5%), seven with Hb SS and five with Hb SC had IDA. Adjusting for
      genotype, children with IDA had significantly higher red blood cell (RBC) counts
      (4.3 x10(9)/l vs 3.0 x 10(9)/l, p < 0.001) and total iron binding capacity (TIBC)
      (65.6 micromol/l vs 55.2 micromol/l, p < 0.004) but significantly lower
      reticulocyte (retic) counts (7.8 % vs 12.2%, p = 0.001) than children without
      IDA. CONCLUSION: Iron deficiency anaemia is a clinical problem which affects
      children with SCD in Jamaica. The higher RBC counts in the IDA group may be due
      to decreased haemolysis and increased red cell survival whilst the lower
      reticulocyte counts may be due to impaired erythropoiesis. These observations
      need to be extended by clinical studies to establish improved diagnostic measures
      for IDA in SCD. Additionally, clinical trials are needed to determine whether
      treatment of IDA in children with SCD reduces morbidity and is associated with
      clinical benefits such as improvements in neurocognitive function.

PMID- 16459511
TI  - The impact of the establishment of a neonatal intensive care unit on the outcome
      of very low birthweight infants at the University Hospital of the West Indies.
AB  - A retrospective analysis of the outcome of inborn very low birthweight infants
      admitted to the neonatal unit of the University Hospital of the West Indies pre-
      (period 1) and post- (period 2) establishment of a neonatal intensive care unit
      was conducted. During the study, 250 infants were admitted to the neonatal unit,
      132 (53%) during period 1 and 118 (47%) during period 2. There was improved
      survival during period 2 when 81 (69%) infants survived compared to period 1 when
      73 (55%) survived (p = 0.02). This increased survival was due to an increase in
      survival of infants weighing 750-999g in period 2 when 17 (65%) infants survived
      compared to 9 (29%) in period 1 (p < 0.05). There was an increase in the number
      of infants ventilated in period 2, 39 (33%) compared to 12 (9%) period 1 (p <
      0.001). Infants who were ventilated in period 2 were less likely to die than
      those ventilated in period 1 (OR 0.05, CI 0.01, 0.66). After controlling for
      gender, weight, gestational age and ventilation, infants born in the second time
      period were less likely to die than those born in the first time period (OR 0.33,
      CI 0.14, 0.76). The establishment of a neonatal intensive care unit has resulted
      in improved survival of very low birthweight infants; further improvement in
      survival of these infants will be dependent on increased accessibility to
      surfactant therapy, initiation of total parenteral nutrition and availability of
      trained personnel.

PMID- 16459512
TI  - The quality of health research reporting by the daily newspapers in Trinidad and
      Tobago.
AB  - In this study, the authors examined the scientific quality of health research
      reported in the three daily newspapers in Trinidad and Tobago. All medical
      research articles published for the period January 1 to December 31, 2003, were
      extracted using a standardized data collection form. The scientific quality of
      the articles was analyzed by taking into consideration various aspects of study
      design, as well as other issues associated with accurate reporting. Of the 321
      eligible articles, 108 were collected from The Trinidad Express, 100 from The
      Trinidad Guardian and 113 from The Trinidad and Tobago Newsday. The percentages
      of articles reporting methodological components consistent with good scientific
      quality were as follows: objective(s) (99.7%), study design (79.8%), study
      procedure (70.1%), selection procedure (70.1%), description of participants
      (87.5%), control/matching group (74.9%), outcome variables (99.4%) and issues of
      validity and reliability (2.5%). In addition, the percentage of articles
      containing aspects of good report writing were as follows: authorship (71.3%),
      authors' affiliation (59.5%), location of the study (25.4%), source of the
      research material (83.1%), duration of the study (27.7%), study setting (72.0%),
      number of participants (74.1%), period in which the study was conducted (12.0%)
      and quantification of the results (66.7%). Observational studies were
      significantly more likely to be reported than experimental studies (71.5% versus
      28.5%). Overall, articles reported in the Trinidad Express and the Trinidad and
      Tobago Newsday were of a better scientific quality than those in the Trinidad
      Guardian. These findings suggest a need to improve the overall scientific quality
      of reported health research in these newspapers by ensuring that reports answer
      the fundamental questions of what, why, who, where, when and how. This might be
      achieved by adopting a structured reporting format similar to that used by many
      peer-reviewed journals.

PMID- 16459513
TI  - A content analysis of health research reported by the daily newspapers of
      Trinidad and Tobago.
AB  - The ability to translate health research into useful information for the
      layperson requires both excellent scientific expertise and communication skills
      that are often foreign to journalist and editors. In this study, we assessed the
      content of health research articles published in the local daily newspapers for
      the year 2003. Issues considered included physical presentation, coverage,
      primary content of the article relative to the country health profile, accuracy
      of the article compared to its original publication, health model (ie
      preventative versus medical/curative) and tone (emotive nature of the report,
      stakeholder addressed). The authors identified 321 eligible articles as follows,
      The Trinidad Express (108), The Trinidad Guardian (100) and The Trinidad and
      Tobago Newsday (113). More than 90% of the reports appeared in the newspapers
      within two weeks of their original journal publication; 10.5% of the articles had
      over 50% newspaper readership coverage. Headlines were prominently displayed for
      70% of articles while 86% of the written text were located on the top right and
      left quadrant of pages where the eye naturally falls during reading. Photographs
      accompanied 36% of the articles. Approximately 72.5% of articles accurately
      reflected the content of the original publication and 67% of them were classified
      as preventative. There were similar proportions of good (45%) and bad (47%)
      articles. The top five predominant themes were nutrition (24.3%), cancer (18.2%)
      women's health (17.6%), heart disease (14.2%) and mental health (10.3%). The
      findings suggest a tremendous effort by journalist and editors to provide
      relevant health information in a timely and attractive manner; however, this
      should not be at the expense of accuracy.

PMID- 16459515
TI  - Variation of homicidal and suicidal behaviour within Trinidad and Tobago and the
      associated ecological risk factors.
AB  - Self destructive behaviour may not occur consistently across a population.
      Identification of variations in homicidal and suicidal behaviour within a country
      can enable specific prevention and public health strategies to be adopted. This
      is significant because morbidity and mortality associated with these behaviour
      patterns is preventable and the affected population is increasingly young adults
      with potentially productive lives. The author sought to identify some of the
      associated risk factors with the behaviours in Trinidad and Tobago, a developing
      island-state in the English-speaking Caribbean, by disaggregating the homicide
      and suicide data available from Police records for distinct geographical regions.
      Spearman rank correlation was used to determine whether any of the variations
      observed could be attributed to social or demographic factors. Homicide and
      suicide were inversely related in many areas of the country. They were both low
      in Tobago. Homicide was positively associatedwith high population density, low
      marriage rates, African ethnicity and showed a trend toward association with
      school drop-out rates. For suicide, low population density, low income, East
      Indian ethnicity and alcohol consumption were significantly correlated. These
      findings underline the benefit of disaggregating national data and suggest
      specific interventions to diminish the occurrence of these harmful behaviour
      patterns in Trinidad and Tobago with possible extension to other similar
      developing countries.

PMID- 16459514
TI  - Characteristics and control of severe hypertension in a specialist, private
      practice in Jamaica.
AB  - OBJECTIVE: To determine the characteristics of patients with severe uncontrolled
      hypertension, in a Jamaican specialist practice; the level of blood pressure
      control achieved in routine clinical practice, and the number/type of
      antihypertensive medications required for blood pressure control. DESIGN: This
      was a retrospective analysis of the medical records of 500 consecutive patients
      presenting to a consultant physician private group-practice between January and
      December 2000. Data were extracted from the records of the 48 patients with
      severe (Grade III) hypertension (WHO/ISH). RESULTS: Fifty per cent (252)
      werefound to be hypertensive, 19% (48) had Grade III hypertension. The patients
      with severe uncontrolled hypertension were of mixed ethnicity, predominantly
      African. Most were less than 65 years old, never smoked cigarettes and were
      overweight/obese. Nearly one-half had LDL cholesterol >3.4 mg/dL. Diabetes (31%)
      and congestive heart failure (21%) were the most common comorbid conditions.
      Fifteen per cent had no illnesses other than severe hypertension. Cardiovascular
      symptoms were predominant, followed by dizziness. Only 19% of patients were
      asymptomatic. More than half of the patients achieved blood pressure > 140/90 mm
      Hg during the study period. Most patients received four drugs and the number of
      drugs prescribed increased with duration of follow-up. The antihypertensive
      medications most prescribed at one year were--angiotensin converting enzyme
      inhibitors (87%), diuretics (78%), calcium channel blockers (63%) and beta
      blockers (69%). CONCLUSION: Severe hypertension was a common problem in the
      specialist private practice in Jamaica. Most patients had cardiovascular
      symptoms, were dyslipidaemic and required four or more antihypertensive drugs for
      adequate long-term control.

PMID- 16459516
TI  - Spectrum of oral and maxillofacial surgical procedures in Kano, Nigeria.
AB  - The goal of the maxillofacial surgeon is to correct facial deformity while
      eradicating surgical diseases, prevent recurrence or complication and restore
      function. The aim of this paper is to review the surgical procedures carried out
      in a new tertiary teaching hospital. A retrospective study of patients with
      maxillofacial surgical diseases seen at the Department of Dental and
      Maxillofacial Surgery, Aminu Kano Teaching Hospital, Kano, Nigeria, between 2001
      and 2003, was conducted. A total of 87 patients had various (primary and
      secondary) surgical procedures during the period under review. There were 51
      males and 36 females, a male to female ratio of 1:0.61 with an age range of 3
      days to 90 years and a mean age of 34.5 years. The majority of the patients were
      in the lower socio-economic group. Reduction and immobilization of the jaw
      fractures (n = 21, 23.3%) was the most common, followed by transosseous wiring (n
      = 12, 13.3%). The most common complications were malocclusion (n = 14, 29.8%) and
      facial defects (n = 12, 25.5%). Reduction and immobilization, and tumour surgery
      of the jaws seem to be the most common surgical procedures while osteotomy was
      the least. Reduction and immobilization with simple arch bars appeared to be very
      effective, more so when the patients could not afford more modern methods of
      treatment. Reconstructive surgeries of ablated jaws are advocated in view of the
      devastating aesthetic and psychosocial effects that these have on the patients.

PMID- 16459517
TI  - Blood pressure, heart rate and temperature variability during periodontal
      surgery.
AB  - The aim of the present study is to investigate changes in blood pressure, pulse
      rate and temperature before and after periodontal surgery. The study included 127
      normal healthy patients (43 males, 84 females) with age range 9 to 65 years (mean
      age: 26 +/- 12 years) who underwent periodontal surgery. After administration of
      a local anaesthetic agent (Ultracain DS) containing 0.06 mg adrenaline, the blood
      pressure, pulse rate, and temperature were measured. Based on the type of
      operation, the patients were divided into four groups. Statistically significant
      changes (as decreasing) in all parameters were observed (blood pressure: systolic
      111.3 +/- 20.1, diastolic 67.7 +/- 13.1, pulse rate: 87.8 +/- 14.9, temperature:
      36.3 +/- 0.3 ) but these changes were significantly decreased after operations
      (blood pressure: systolic 105.9 +/- 19. 7, diastolic 62.6 +/- 11.3, pulse rate:
      84.01 +/- 13.1, temperature: 36.2 +/- 0.3). And without age group differentiation
      in all parameters, statistically significant decreases were found among females
      (p < or = 0. 05).

PMID- 16459518
TI  - Non-syndromal multiple buried supernumerary teeth: report of two cases from the
      English-speaking Caribbean and a review of the literature.
AB  - Multiple supernumerary teeth affecting all four quadrants of the jaw are a rare
      dental anomaly which has become a chance finding on routine dental panoramic
      tomography (DPT). In this paper, two cases from the English-speaking Caribbean
      are reported. The role of radiography in the diagnosis and management of this
      rare developmental dental anomaly is emphasized. The paper stresses the
      importance of ruling out associated syndromes such as Gardner's Syndrome,
      cleidocranial dysostosis and cleft lip and palates, as multiple supernumerary
      teeth are usually related to such conditions. There is a review of the literature
      as it relates to supernumerary teeth.

PMID- 16459519
TI  - Aggressive infantile (desmoid-type) fibromatosis of the maxilla: a case report
      and new classification.
AB  - This paper describes the clinical, radiographic and histologic findings of an
      aggressive infantile (desmoid-type) fibromatosis of the face in a seven-year-old
      black Jamaican male. This condition is rare in the head and neck region and its
      occurrence in the maxilla is exceptional. The differential diagnosis, management
      and long term follow-up of this case are also mentioned The need for a less
      aggressive surgical management in this child and long-term follow-up is stressed.
      Also, its occurrence in someone of African descent has not been reported
      previously. The absence of recurrence, eight years after surgery is significant.
      This paper discusses the differential diagnosis and treatment of aggressive
      infantile fibromatosis and suggests a classification of the condition.

PMID- 16459520
TI  - Streptococcus intermedius liver abscesses and colon cancer: a case report.
AB  - Certain species of bacteria are known to be associated with colorectal cancer. We
      report a case of adenocarcinoma of the colon with bacteraemia and liver abscesses
      due to Streptococcus intermedius. The isolation of this organism should prompt
      investigation for colorectal neoplasm, which may be present but asymptomatic,
      without metastases, and therefore at a curative stage.

PMID- 16459521
TI  - Bilateral psoas abscess in a case of granuloma inguinale.
AB  - The authors present a case of disseminated granuloma inguinale with bilateral
      psoas abscesses. Infection with calymmatobacterium granulomatis is usually
      localized to the genital organs but rarely may be disseminated. A search of the
      literature revealed that only two cases of psoas abscesses due to
      calymmatobacterium granulomatis were previously reported

PMID- 16459522
TI  - Spontaneous haemo-pneumothorax: a rare but life-threatening phenomenon.

PMID- 16459524
TI  - The story of cardiac defibrillation.

PMID- 16459523
TI  - Bilateral Krukenberg ovarian tumours complicated by pregnancy in an Antiguan
      woman of African ethnicity.

PMID- 16459525
TI  - Elderly in India--needs and issues.

PMID- 16459526
TI  - Outpatient oral anticoagulant management--an audit of 82 patients.
AB  - OBJECTIVE: Use of oral anticoagulants for thrombotic diseases has been increasing
      steadily over the years. Management practices however, are far from uniform. We
      conducted a retrospective audit among outpatients on oral anticoagulant therapy
      to assess treatment practices and overall control of anticoagulation. METHODS:
      Case records of 82 patients who were on anticoagulant therapy for a minimum
      duration of three months were reviewed. Information on pre-therapeutic assessment
      of patients, therapeutic control and complications seen during the course of
      treatment was recorded. RESULTS: Case notes of 43 males and 39 females with a
      mean age of 47.5 +/- 14.6 years, on oral anticoagulant treatment were evaluated.
      Treatment duration ranged from 3 months to 7 years for a total of 258.7 patient
      treatment years. Pre-therapeutic assessment of patients was inadequate with only
      baseline hematological and renal parameters available for most patients. Of a
      total of 1631 prothrombin time ratios and International Normalized Ratios
      recorded, only 17.8% were in the therapeutic range with 73% being sub
      therapeutic. Sixteen (19.5%) patients had treatment related complications. The
      number of thrombotic and hemorrhagic events per 100 patient treatment years was
      3.4 and 2.7 respectively. CONCLUSIONS: Pre-therapeutic assessment of patients was
      inadequate. The overall therapeutic control was poor with patients in a state of
      underanticoagulation for most period of anticoagulant treatment. The complication
      rate was also unacceptably high. There is a need to reassess management practices
      of patients on long term oral anticoagulation with strict adherence to standard
      accepted guidelines to make this therapy more effective and safer for patients.

PMID- 16459527
TI  - What influences outcome of patients with suicidal hanging.
AB  - AIM: Suicidal hanging is an uncommon medical emergency with significant
      neurological morbidity. The aim of the study was to identify factors that have a
      bearing on the final outcome. MATERIALS AND METHODS: Retrospective analysis of 37
      consecutive cases of suicidal hanging admitted to our ICU from July 1996 -
      December 2002 was performed. Outcome at discharge was defined as good (complete
      neurological recovery) or poor (death or incomplete neurological recovery). Three
      clinical variables (at presentation) namely Glasgow Coma Scale (GCS) at
      presentation, time lapse (in hours) from the incident to arrival at our hospital
      and the presence of Hypotension (defined as a systolic blood pressure < or = 90
      mm Hg) at admission were recorded and tested individually for an association with
      the outcome. Statistical analysis was done using the Odds ratio (OR +/- 95%
      Confidence Intervals) and Chi-square test of significance for categorical data.
      RESULTS: Patients with suicidal hanging constituted < 1% of ICU admissions (mean
      age 27 years). 34/37 survived giving a survival rate of 92%. Of those who
      survived, 31 patients (91%) had complete neurological recovery at the time of
      discharge from hospital. Among those who presented <4 hours of the incident (25
      patients), 2 had an adverse outcome as compared to 4/10 patients who presented 4
      hours or more after the incident (OR 7.6,95% CI 1.12-52.3). A low GCS (GCS <7) at
      presentation was also statistically associated with a poor outcome (OR 10.4, 95%
      CI 1.08-102.1). Hypotension was present in approximately 33% of patients (12/37)
      at presentation. Of these 12 patients, 3 had an adverse outcome as opposed to 3
      patients among the remaining 25 (OR 1.6, 95% CI 0.41 - 14.47, NS). CONCLUSIONS:
      Suicidal hanging is an unusual medical emergency that is common among young
      individuals in developing countries. Our study indicates that a delayed
      presentation to a medical facility and a low GCS at presentation predict a poor
      outcome.

PMID- 16459528
TI  - Characteristics of gestational diabetic mothers and their babies in an Indian
      diabetes clinic.
AB  - AIMS AND OBJECTIVES: To compare clinical and metabolic features of mothers with
      gestational diabetes (GDM) and their offspring with those in non-diabetic
      pregnancies at the King Edward Memorial Hospital, Pune, India. MATERIALS AND
      METHODS: Antenatal information was obtained from hospital records. GDM was
      diagnosed by 75 g OGTT (Oral Glucose Tolerance Test) in clinically high-risk
      women. Anthropometric measurements of mother and the babies were recorded within
      24h of delivery and a maternal blood sample collected for hematological and
      biochemical measurements. RESULTS: Between the period Jan 1998 to December
      2003,265 women with gestational diabetes were treated in our Unit. Forty nine
      percent had first-degree relatives with diabetes. Compared to non-diabetic
      mothers (n=215) GDM mothers were older (29.0 vs. 26.0y, p<0.001), more obese
      (body mass index- BMI 26.0 vs. 22.0 kg/m2, p<0.001), centrally obese (Waist hip
      ratio-WHR 0.89 vs 0.86, p<0.001), adipose (sum of 4 skinfolds 98.4 vs. 61.4 mm,
      p<0.001) and had higher blood pressure (127/80 vs. 122/70 mmHg, p<0.001). GDM
      mothers had higher concentrations of plasma triglycerides (195.0 vs. 153.0 mg/dl,
      p<0.01); blood hemoglobin (11.7 vs 10.9 g/dl, p<0.001) and higher platelet count
      but lower concentration of HDL cholesterol and albumin. Sixty percent GDM mothers
      and 34% of non-diabetic mothers were delivered by caesarean-section, 23% of GDM
      mothers delivered pre term (<37 wk). Despite the smaller gestation, babies of GDM
      mothers were heavier (BW 2950.0 vs. 2824.0g, p<0.001, adjusted for gender),
      longer (48.9 vs. 48.0 cm, p<0.01) and more adipose (sum of 2 skinfolds 10.5 vs.
      8.5 mm). Only 5% of babies born to GDM mothers weighed > 4000 g but 30% were
      >90th centile of birth weight of babies born to non-diabetic mothers. Babies of
      GDM mothers suffered higher neonatal morbidity. CONCLUSIONS: GDM mothers in urban
      India are more obese and more adipose than non-diabetic mothers, frequently have
      a family history of diabetes and show metabolic features of insulin resistance
      syndrome, suggesting high cardiovascular risk. Neonates of GDM mothers are
      heavier, longer and more adipose than those born to non-diabetic mothers, and
      suffer higher neonatal morbidity.

PMID- 16459529
TI  - Vein of Galen malformation.

PMID- 16459530
TI  - Pre sternal cold abscess.

PMID- 16459531
TI  - Emerging geriatric challenge.
AB  - India is a vast country with diversity, both physical and cultural. 72% of
      World's second largest population live in rural experiencing varying degrees of
      socioeconomic change. However, there is no nationwide registry of older people
      and exact statistics about elderly population is not available. Community-based
      data on morbidity and disability are also not available. India is one of the few
      countries in the world where men out number women at all ages till about 70 years
      and only in very old age (80+) there are more women than men. One of the main
      social effect of extension of life in later years is the extended period of
      widowhood for women mainly due to cultural practice of men marrying younger women
      and widow marriage as well as divorce are uncommon. Much progress has been made
      in the health care services in the last 50 years giving much emphasis to mother
      and child programme with special emphasis on controlling population. But elderly
      population has been neglected, there is no separate ward for elderly in
      hospitals, no specialized courses in the Universities for training doctors and
      nurses for elderly care. Recently, Indian Medical Association has organized an
      ambitious project for rural elderly with emphasis on Geriatric care. Still
      recently, emphasis has been given for developing infrastructural facilities
      including creating training, courses on Geriatric Medicine and integrating with
      alternative system for better care of elderly. However, due to increasing
      awareness of policy makers to multiple issues related to aging, some progress has
      been made like old age pension scheme, income tax rebate for elderly, old homes
      and day care centers and law to help retired citizens in evicting tenants etc.
      but environment is not as elderly-friendly as in European countries, as the State
      is not likely to have adequate resources in the presence of other priorities in
      the country.

PMID- 16459533
TI  - Sirolimus: a new immunosuppressant.
AB  - Though organ transplantation has evolved in many a ways over the years, it is not
      without the disadvantage of causing rejections. Cyclosporin, azathioprine and
      corticosteroids are time tested and efficacious; however each is accompanied with
      its own array of disadvantages. Sirolimus is a relatively new immunosuppressant
      isolated from a macrolide antibiotic. It may have a beneficial role in
      prophylaxis of rejection as well as treatment of refractory rejection. It also
      has antifungal, antitumor and anti-smooth muscle proliferative roles.

PMID- 16459532
TI  - Cancer related thrombophilia: clinical importance and management strategies.
AB  - Acquired thrombophilic state associated with a significant risk of thrombosis is
      frequently encountered in malignancy. Venous and arterial thromboembolism is a
      common complication and patients with cancer, also present with a hypercoagulable
      state, even in the absence of thrombosis. Furthermore, clotting activation may
      play a role in tumor progression. The pathogenesis of thrombosis in cancer is
      multifactorial; however, a relevant role is attributed to the tumor cell capacity
      to interact with and activate the host hemostatic system. Among other factors,
      the prothrombotic action of antitumor therapies is also important. Thrombotic
      events can influence the morbidity and mortality of the underlying disease.
      Therefore, preventing these complications in cancer patients is a clinically
      relevant issue. Recently, new approaches to the prevention and cure of thrombosis
      in cancer have been investigated, and the hypothesis that the strategies to
      inhibit clotting mechanism may favorably affect malignant disease is gaining
      increasing interest. In this article the various aspects of the complex
      relationship between thrombosis and cancer, from pathophysiology to therapy, are
      reviewed.

PMID- 16459534
TI  - Consent--its medico legal aspects.
AB  - One of the duties of a doctor towards his patients is to obtain consent before
      any medical examination. Any such examination without prior consent amounts to an
      assault on the patient. Consent is defined under Indian Contract Act (because
      Doctor Patient relationship isa contract) as "two or more persons are said to
      consent when they agree to the same thing in the same sense." Consent may be
      implied, expressed or informed depending upon the circumstances. But the consent
      of the patient is not required in situations like medical emergency, for
      vaccination etc. If the patient is not medically or legally competent to give
      consent, the consent of the parents or guardians or any person present at the
      time with the patient can be taken. Any research on a potential subject, removal
      of organs for transplantation, publication of information obtained during medical
      examination also require consent of the concerned person.

PMID- 16459535
TI  - Type 1 diabetes mellitus in homozygous sickle cell anaemia.
AB  - For reasons unknown, the association of diabetes mellitus with sickle cell
      anaemia is uncommon. A patient of sickle cell anaemia with diabetes mellitus,
      complicated with ketoacidosis is being reported in view of its rarity.

PMID- 16459536
TI  - An imaging study of body composition including lipodeposition pattern in a
      patient of familial partial lipodystrophy (Dunnigan type).
AB  - Familial Partial Lipodystrophy, Dunnigan type (FPLD), is characterised by loss of
      subcutaneous fat from the limbs and an excessive accumulation of fat on the neck,
      shoulder girdle and face. Affected individuals have insulin resistance,
      dyslipidaemia and early cardiovascular events. Body composition (BC) with details
      of adipose tissue distribution were studied by Dual-Energy X-ray Absorptiometry
      (DEXA) and Magnetic Resonance Imaging (MRI) ina heterozygote for the FPLD
      mutation LMNA R482W, and in an age, sex and body mass index (BMI) matched normal
      control. DEXA revealed a marked decrease in total as well as regional fat
      percentage in the patient compared to a normal control. Marked reductions in
      subcutaneous fat in the extremities with substantial lipodeposition in the nape
      of the neck were confirmed with. MRI. The importance of increased perinephric,
      retroperitoneal and intermuscular fat in the thighs found in this patient, needs
      to be explored vis-a-vis the pathogenesis of insulin resistance found in FPLD.

PMID- 16459537
TI  - Invasive aspergillosis producing painful ophthalmoplegia.
AB  - Painful ophthalmoplegia is caused by the lesions of orbital apex and anterior
      cavernous sinus. Cavernous sinus syndrome can be produced by intracranial
      invasive aspergillosis. A case of painful ophthalmoplegia due to invasive
      aspergillosis caused by Aspergillus niger in a diabetic patient is presented.

PMID- 16459538
TI  - Subungual erythema in lymph node tuberculosis with erythema nodosum.
AB  - We encountered a case of tuberculous lymphadenitis with erythema nodosum
      presenting with an unusual manifestation as subungual erythema in all the digits.
      Relevant literature and the possible explanation for the subungual erythema have
      been discussed.

PMID- 16459539
TI  - Disseminated histoplasmosis with reactive haemophagocytosis presenting as PUO in
      an immunocompetent host.
AB  - Disseminated histoplasmosis (DH) with reactive haemophagocytosis has been
      described in literature mainly in immunocompromised hosts. Only sporadic case
      reports exist in immunocompetent hosts. Here, we present a rare case of DH with
      reactive haemophagocytosis in an immunocompetent host presenting as PUO.

PMID- 16459540
TI  - Plus minus lid syndrome with ataxia.
AB  - Plus minus lid syndrome is an ocular syndrome characterized by unilateral ptosis
      and contralateral lid retraction. Also when the ipsilateral lid is raised
      manually, the contralateral retracted lid does not revert. This patient presented
      with features of plus minus lid syndrome with ataxia due to a vascular
      mesencephalic lesion.

PMID- 16459541
TI  - Medical philately (medical personalities on stamps). Ambroise Pare (1510-1590).

PMID- 16459542
TI  - Diagnosing rubella: fallacies and pitfalls.

PMID- 16459543
TI  - Unilateral chorioretinitis: an initial manifestation of subacute sclerosing
      panencephalitis.

PMID- 16459544
TI  - Ocular changes in infectious diseases.

PMID- 16459545
TI  - Fungi and nematodes occurring in different composts used in Uruguayan
      agriculture.
AB  - Forty three thermophilic, thermotolerant and mesophilic fungal species and
      nematodes from five trophic groups were found in four compost types. Aspergillus
      fumigatus and A. niger were the most frequent species. Plant pathogenic fungi
      viz. Fusarium oxysporum, F. acuminatum, F. nygamai and F. solani were found in
      some of the composts in low frequency. The most abundant species of nematode
      corresponded to bacterivores. Tylenchus, a phytophagous nematode was scarcely
      found.

PMID- 16459546
TI  - Influence of sublethal ammonia toxicity on some physiological parameters of Labeo
      rohita (Hamilton-Buchanan) fingerlings.
AB  - Fingerlings of Labeo rohita subjected to sublethal unionized ammonia (0.132mg/l)
      for 30 days exhibited significant changes. Increase in haemoglobin, haematocrit,
      plasma cortisol, plasma glucose, plasma cholesterol and plasma lactic acid levels
      whereas, decrease in plasma chloride, liver and muscle glycogen, hepatosomatic
      index and DNA/RNA ratio of muscles with stable plasma protein was observed.
      Metabolic recovery was not observed within 30 days of exposure.

PMID- 16459547
TI  - Using respirometer in biodegradation phenomenon of natural organic matters.
AB  - This study conducted in monitoring respirometer oxygen consumption of aerobic
      microorganism during biodegradation processes of ozonated organic matters, which
      can estimate both biodegraded efficiency and coefficient of natural organic
      matters (NOMs) in water source. It can be proposed that different ozone dosage
      might change biodegradation characteristics of organic matters. The result
      reveals that higher ozone dosage may cause higher biomass yield coefficient of
      microorganism, and cultured microorganism may easily utilize biodegradation
      organic matters (BOMs) produced by ozonation, finally increasing overall removal
      efficiency. Therefore, using respirometer to evaluate the production of BOMs by
      ozonation before the biological treatment is effective for controling ozone
      dosage and enhancement of NOMs removal by biological processes.

PMID- 16459548
TI  - Tree species diversity and composition in logged and unlogged rainforest of
      Kudremukh National Park, South India.
AB  - Species composition and diversity in logged and unlogged forests were assesed to
      understand the regeneration of the residual stand twenty years after logging in
      Kudremukh National Park, South India. Relative density, frequency and basal area
      were measured by Point Centered Quarter method to calculate the diversity and
      stand quality. The logged forest harbored lower stem density of mature trees (508
      ha(-1)) than unlogged ones (630 ha(-1)). Indeed, logging operations increased the
      species diversity in the regenerative phase (seedling phase) due to the creation
      of larger canopy gaps. The extra radiation reaching the ground, facilitated the
      colonization of early and late secondary species. Ramakrishanan Index of Stand
      Quality (RISQ) values in logged forest was higher in comparison with unlogged
      forest, indicating the dominance of early and late secondary species, especially
      at sapling phase. The light demanding secondary forest species contribute higher
      percentage to the overall tree population in logged forest. It is observed from
      the study that a sufficient period of felling cycle should be practiced to
      reinstate the same set of species prevailed before logging.

PMID- 16459549
TI  - Effects of stream hydraulic conditions on foraging strategies of false dace,
      Pseudorasbora parva, in the lentic ecosystem.
AB  - The effects of current velocity on the foraging behavior of false dace,
      Pseudorasbora parva, were examined in a zero velocity (stagnant) condition, and
      at four flow rates (5, 7, 11 and 16 cm per second). In stagnant water, the fish
      displayed a cruise-searching pattern, but they used a drift-feeding foraging
      tactic in flowing water. The shape of the transverse field of reaction field was
      elliptical in the stagnant condition, whereas their downward regions were
      restricted under the flowing conditions. The fish had a blind spot oriented
      directly in front of their reaction field. Although the relative swimming speed
      (with considering the against current velocity) increased with increasing flow
      velocity, the absolute search speed (ignore the against current velocity) showed
      about 1.2 fish body length per second at stagnant water and low flow velocity.
      The results of feeding rates showed stop-and wait (driff-feeding) foraging
      strategy is more efficient in flowing water because prey drift directly towards
      the fish and prey easily detected.

PMID- 16459550
TI  - Development of ground vegetation under exotic tree plantations on restored coal
      mine spoil land in a dry tropical region of India.
AB  - Restoration of mine spoil is a prime need for coal industry. The study of ground
      cover vegetation provides essential information about the species diversity and
      their successional trends during the restoration. The present study was conducted
      to analyze the structure and biomass accumulation of ground vegetation developing
      in different plantation stands of an opencast coal mine spoil in a dry tropical
      region. Different plantation stands showed variations in species diversities.
      Exotic herbs were more dominant in comparison to native herbs. Pennisetum
      pedicillatum, an exotic herb showed maximum Importance Value Index in most of the
      plantation stands. Total number of species varied between 12-18 in different
      plantation stands. Speces richness and evenness increased with increasing age of
      the plantations. Variations in total biomass accumulation of ground vegetation
      were also significant among different plantations. These results suggest that
      reforestation programme with exotic species on coal mine spoil has been
      successful in colonization of ground vegetation under different plantations.
      Gravellia pteridifolia plantations showed most successful ground cover among
      different plantation stands.

PMID- 16459551
TI  - Growth and amylase production by Aspergillus oryzae during solid state
      fermentation using banana waste as substrate.
AB  - Aspergillus oryzae, isolated from the starch rich litter soil, produced amylase
      when banana fruit stalk was used as substrate in a solid state fermentation
      system. The effects of incubation period, pH, temperature and various carbon
      sources on the production of amylase were studied. A maximum yield of 380U/mg was
      recorded on 96th hour of incubation. The amylase is tolerant to wide range of
      initial culture pH values (3 to 8) and temperature (25 to 35 degrees C), with an
      optimum pH of 5 and temperature of 35 degrees C. In SSF addition of starch (1%)
      increased the amylase production, when compared with other carbon sources used.

PMID- 16459553
TI  - Biosorption of zinc (II) using Spirogyra species from electroplating effluent.
AB  - Zinc was removed from the metal plating effluent with the biosorbent consisting
      of filamentous algae Spirogyra sp. The sorption was pH dependent with best
      adsorption at pH 2.5. The metal uptake increased from 3.9% (for no dilution) to
      36.8% (for 10 times dilution), indicating that sorption increased with dilution
      of sample. The adsorption was faster at initial contact time, gradually decreased
      and remains constant after certain optimum time. Percentage removal of zinc
      increased from 20.3% to 63.6% with increase in the temperature from 25 degrees C
      to 35 degrees C but further increase resulted in the decrease in adsorption.
      Freundlich isotherm was applied and it holds good for the adsorption data.

PMID- 16459552
TI  - Larvicidal potential of Nerium indicum and Thuja oriertelis extracts against
      malaria and Japanese encephalitis vector.
AB  - Ethanolic and acetone extracts of Nerium indicum and Thuja orientelis have been
      studied against III instar larvae of Anopheles stephensi and Culex
      quinquefasciatus. Ethanolic extract of N. indicum is found more effective than
      its acetone extract against anopheline larvae with LC50 values of 185.99 and
      148.05 ppm for former and 229.28 and 149.43 ppm for the later after 24 and 48 hrs
      of exposure. The acetone extract with LC50 values of 209.00 and 155.97 ppm is
      more effective in case of culicine larvae than its ethanolic extract with LC50
      494.07 and 194.49 ppm after 24 and 48 hours of treatment. Ethanolic extract of T.
      orientelis is more effective against both the larval species with LC50 values of
      13.10 and 9.02 ppm after 24 and 48 hours for anopheline and 22.74 and 16.72 ppm
      against culicine larvae. The acetone extract showed LC50 values of 200.87 and
      127.53 ppm against anopheline and 69.03 and 51.14 ppm against culicine larvae.
      Thus ethanolic extract of T. orientelis is an ideal potential larvicide for both
      types of mosquito larvae.

PMID- 16459554
TI  - Trace element biomonitoring by leaves of Populus nigra L. from Western Anatolia,
      Turkey.
AB  - The West Anatolian Region is one of the most important areas for
      industrialization, population density and traffic in Turkey. Therefore, the
      leaves of Populus nigra L. (Salicaceae), which are used as biomonitor to
      investigate the levels of the trace elements Cd, Pb, Fe, Zn and Cu, were sampled
      at 30 locations having different pollution levels in the region. The
      concentrations of elements were determined by atomic absorption spectrometry. The
      samples were collected at both reference and contaminated locations where iron
      was found as the priority element. The strong association between a gradient of
      contamination and concentration in all samples tested indicates that they are
      reflecting well the environmental changes, and that they appear as appropriate
      biological indicators of heavy metal contamination.

PMID- 16459555
TI  - Inhibitory effect of high soil pH on growth and mineral metabolism of rice and
      its reversal by zinc.
AB  - Increasing soil pH retarded growth, tillers and bio-mass production of rice
      cultivar Sarjoo-52. Application of 10 to 15 kgZn ha(-1) increased the bio-mass by
      33 to 41% at pH 8.5 and 27 to 32% at pH 10.3. Panicle length, rachis branches,
      total spikelets, filled grains, grain size were all adversely affected to the
      tune of 19, 23, 40, 74 and 21%, respectively by higher soil alkalinity at pH
      10.3. Alkalinity resulted in 19, 31 and 65% spikelet sterility which reduced to
      3, 21 and 55% at pH 8.5, 9.5 and 10.3, respectively by Zn applied @ 15 kg ha(-1).
      Grain yield reduced to 50% at pH 10.3 but Zn in general, raised the yield levels
      by 1.6 to 2.3, times. The chlorophyll decreased by 36 to 50% whereas carbonic
      anhydrase activities decreased only by 13% due to increase in soil sodicity and
      alkalinity. Further, increase in pH caused significant decrease in Zn, Ca, Mg, P
      and K concentrations but phenomenal rise in Na content Zinc application, apart
      from increasing tissue Zn content, elevated Ca :Na and K :Na ratio resulting in
      improved growth and yield of rice under soil sodicity and alkalinity.

PMID- 16459556
TI  - Studies of VA-Mycorrhizal fungi associated with some weed plants in sugar mill
      effluent soils.
AB  - This study is to isolate the effluent strain of VAM fungi from polluted soils of
      sugar mill effluents. Analysis showed that pH and EC was more but the organic
      matter is less when compared to non-polluted soils. Even though there was low P
      content that enhances the mycorrhizal infection, the percent of root colonization
      was less than 75% in polluted study site. The number of VAM propagules and its
      distribution were also greatly affected due to various factors. Nine different
      VAM species were isolated and identified from the polluted study site. Using
      Allium cepa L. as the host plant the efficiency of the native effluent tolerant
      strains of VAM fungi isolated from the polluted study site was determined.
      Highest growth rate, high dry weight of gram per plant and increased growth was
      observed in the order of Glomus intraradices followed by Gigaspora margarita and
      Glomus fasciculatum. Consequence of the study clearly showed that Glomus
      intraradices was the efficient strain in sugar mill effluent polluted areas.

PMID- 16459557
TI  - Glutathione antioxidant status of frozen meat samples.
AB  - Lipid oxidation is a process, which results in rancidity and deterioration of
      fats posing a major problem in food industry. Antioxidants are of interest, which
      presumably protects food from oxidative deterioration during storage. The
      glutathione antioxidant system of different meat samples were noticed for six
      months under refrigerated storage. Activity of glutathione reductase (GR) and
      level of glutathione (GSH) decreased during six months storage in all the four
      meat samples. The glutathione peroxidase (GSH-Px) and glutathione-S-transferase
      (GST) activity increased gradually during storage. It seems possible that
      glutathione antioxidant system protected the meat samples against quality loss
      during its storage.

PMID- 16459558
TI  - Effects of azadirachtin on mortality, fertilization, and swimming speed in larvae
      of the cane toad, Bufo marinus (Anura: Bufonidae).
AB  - Experiments were conducted to assess the effects of azadirachtin (AZ) on survival
      capacity, fertilization success, and swimming speed in larval stages of the cane
      toad, Bufo marinus . LC50 values (96-hr) for various larval stages exposed to
      0.50 mg/l AZ were as follows: 5.35 (stage 12), 5.77 (stage 16), 787 (stage 20),
      13.43 (stage 24), and 21.54 (stage 30). Tadpoles did not exhibit any apparent
      disorientation or production of mucous in response to AZ concentrations ranging
      from 0.3 to 0.5 mg/l. Mortality was significantly higher at 0.50 mg/l AZ than at
      lower concentrations. At 0.50 mg/l, mortality rate decreased significantly from
      36% for stage 12 tadpoles, to 24% for stage 20 tadpoles. Mortality for early
      stages (stage 12) dropped significantly, from 36% at 0.50 mg/l, to 21% at 0.40
      mg/l AZ There were no significant differences in percent mortality for any
      developmental stage at an AZ concentration of 0.3 mg/l, or for controls (no AZ).
      Exposure of gametes to 0.30 mg/l AZ did not reduce fertilization success as
      compared to controls (89.8 vs. 83.7%). At 0.40 mg/l, percent fertilization
      decreased significantly (68.8%). This effect was even more pronounced at 0.50
      mg/l. No significant difference was found in swimming speeds between controls and
      subjects exposed to 0.30 mg/l AZ. However, at a concentration of 0.40 mg/l,
      tadpoles required a significantly longer period of time to swim a distance of 140
      cm as compared to controls. The potential impact of AZ on amphibian populations
      is discussed.

PMID- 16459559
TI  - Growth of Brassica juncea under chromium stress: influence of siderophores and
      indole 3 acetic acid producing rhizosphere bacteria.
AB  - Plant growth promoting rhizobacterial (PGPR) strains A3 and S32 have been shown
      to promote the growth of Brassica juncea under chromium stress which has been
      related to the microbial production of siderophores and indole 3 acetic acid
      (IAA). The aim of the present study is to evaluate the importance of siderophores
      and IAA producing PGPR on the growth of Brassica juncea under chromium stress.
      The production of IAA and siderophores were observed in the strains A3 and S32,
      respectively. Both PGPR strains promote the growth of Brassica juncea under
      chromium stress. The maximum growth was observed in plants inoculated with
      siderophores producing strain 32. Both the bacterial inoculum did not influence
      the uptake of chromium by plants. The present observation showed that PGPR
      isolates A3 and S32 are capable of protecting the plants against the inhibitory
      effects of chromium by producing the siderophores and IAA.

PMID- 16459560
TI  - Changes in tissue cholesterol and serum cortisol level during four reproductive
      phases of the male freshwater fish, Notopterus notopterus.
AB  - The tissue cholesterol and serum cortisol changes during four reproductive phases
      has been studied in the freshwater fish Notopterus notopterus of male sex during
      four phases, preparatory (January - March), prespawning (April - May), spawning
      (August - September) and post spawning (November - December). The cholesterol
      content of the testis and liver increased during preparatory phase and maximum
      content of cholesterol was during spawning phase. The serum cortisol estimated by
      radioimmunoassay (RIA) technique which indicated that the level of the hormone
      was high during pre-spawning and spawning phases compared to other two phases.
      The increase in cholesterol during preparatory and spawning phases may be because
      of increase in cortisol synthesis needed for testicular growth and
      spermetogenesis during these phases. The gonadosomatic index (GSI) also increased
      during these phases.

PMID- 16459561
TI  - Infectivity and efficacy of Glomus aggregatum and growth response of Cajanus
      cajan (L.) Millsp. in flyash amended sterile soil.
AB  - In the present investigation a pot culture experiment was conducted using
      sterile, phosphorus deficient soil to study the effect of flyash at 3 different
      concentrations (10g, 20g and 30g flyash/kg soil) on the infectivity and
      effectiveness of VAM fungus Glomus aggregatum in pigeonpea (Cajanus cajan (L.)
      Millsp.) cv Maruti. The flyash amendment in soil at all the 3 different
      concentrations was found to affect significantly the intensity of VAM fungal
      colonization inside the plant roots and also suppressed the formation of VAM
      fungal structure (vesicles and arbuscules) completely at higher concentration
      (30g flyash/kg soil). The response of the pigeonpea plants, as judged by their
      higher and dry weight, under the influence of flyash amendment in VAM fungus
      infested soils was found to be considerably less (though not significant enough)
      when compared to the control plants (without flyash) that have otherwise shown
      significant increase in growth over the plants without Glomus aggregatum
      inoculation. However, flyash amendment without VAM inoculation was also found to
      enhance the growth of plants as compared to control plants (without flyash and
      VAM inoculum).

PMID- 16459562
TI  - Effect of surfactants on Fenton's reagent-mediated degradation of Kraft black
      liquor.
AB  - One of the limitations of the biodegradation of hydrophobic chemical compounds,
      like lignins, is their low solubility in the aqueous solution where this process
      takes place. To resolve this problem, surfactants have been used to improve the
      solubility of these hydrophobic compounds. In this investigation, we studied the
      effect of surfactants (anionic, cationic, and non-ionic) on the treatment of
      Kraft black liquor with Fenton's reagent. In the Fenton reaction, H2O2 (two
      different concentrations, 10 mM and 20 mM), FeCl2 (1 mM) and surfactant solution
      (10%) were used. Black liquor degradation was determined by UV/Visible
      spectrophotometry and by measuring phenolic groups. In the presence of Fenton's
      reagent, the optimum conditions for the oxidative degradation of black liquor
      were 10 mM H2O2, 1 microL of 10% solution of anionic surfactant (SDS). The
      importance of the use of surfactants for preparing black liquor for subsequent
      Fenton's reagent-mediated degradation was discussed.

PMID- 16459563
TI  - Potential of Anopheles philippinensis-nivipes complex mosquitoes as malaria
      vector in north-east India.
AB  - Anopheles philippinensis-nivipes complex mosquitoes, captured in outdoor human
      landing catches and light traps in human dwellings from four different sites in
      Assam state and adjoining areas, were examined (n=1670) for the presence of
      circumsporozoite antigen (CSA) through enzyme linked immunosorbent assays
      (ELISA), using species specific capture monoclonal antibodies, of Plasmodium
      falciparum and two Plasmodium vivax polymorphs (Pv 210 and VK 247). In ELISA, 28
      pools were found positive for CSA that accounted for minimum sporozoite rate of
      1.7% (95% CI 1.11-2.41). Twenty five percent (7/28) of the positive pools were
      reactive for P. falciparum and between the two polymorphs of P. vivax, VK 247 was
      predominant with 77% (20/26) of all P. vivax positive pools. Results were
      suggestive of most likely involvement of Anopheles philippinensis-nivipes complex
      mosquitoes in malaria transmission in north-east India.

PMID- 16459564
TI  - Cybil induced hepatobiochemical changes in wistar rats.
AB  - Cybil, 25%EC formulation of Cypermethrin, induces biochemical changes in the
      liver of wistar rats after oral intubation of the same at acute (one day) and
      subacute (7, 14 and 21 days) levels. The changes were tallied with the controls
      run simultaneously. LD50 of Cybil was estimated to be 622mg/kg body weight The
      acute dose is 80mg/kg body weight exposed for one day i.e. 24 hours and subacute
      dose is 4mg/kg body weight exposed for 7, 14 and 21 days. When compared with the
      control values, both the doses enhanced the level of glycogen, cholesterol, total
      lipid and acid phosphatase activities, while decreased activity of alkaline
      phosphatase. Alterations in glycogen, cholesterol, total lipid, acid phosphatase
      and alkaline phosphatase resulted in the impairement in liver physiology.

PMID- 16459565
TI  - Aerobic heterotrophic bacterial diversity in sediments of Rajakkamangalam
      estuary, south west coast of India.
AB  - The abundance of aerobic heterotrophic bacterial population in the sediment
      sample of six experimental stations (S1 to S6) at Rajakkamangalam estuary was
      studied for a period of one year from March, 1998 to February, 1999. The
      important bacterial genera encountered were Pseudomonas, Bacillus, Vibrio,
      Escherichia, Micrococcus, Enterobacter, Salmonella, Aeromonas, Shigella,
      Klebsiella, Proteus, Alkaligenes, Staphylococcus, Citrobacter and Flavobacterium.
      The bacterial population based on numerical counts showed wide fluctuations in
      their distribution at different stations. Among the bacterial genera Pseuaomonas
      was found to be the dominant genus during the experimental period. The
      qualitative and quantitative distribution of microflora in the sediment samples
      are discussed.

PMID- 16459566
TI  - Modification of wood with environmentally friendly chemicals to improve decay
      resistance.
AB  - Turkish pine (Pinus brutia Ten.) solid wood was chemically modified to various
      weight percent gains (WPG) using either acetic, methacrylic, hexanoic and
      succinic anhydrides. Laboratory soil block decay testing using the brown rot
      fungus C. puteana and G. trabeum was performed and weight loss calculated. All
      high degree of modified samples showed good biological resistance and severely
      reduced degradation. Chemical modification of wood is very important for the
      prevention of biodeterioration which are environmentally friendly and also not
      hazardous to human beings.

PMID- 16459568
TI  - Ecofriendly approach of urban solid waste management: a case study of Jalgaon
      city, Maharashtra.
AB  - In India, the traditional methods are used for urban solid waste management.
      These practices are associated with degradation of the urban environment Hence,
      an environmentally sound garbage management system is required for the urban
      waste management. The concept of waste minimization needs to be adopted in such
      systems. It is possible to implement certain corrective measures at collection,
      storage, transport and disposal of urban solid waste to minimize the adverse
      impacts on the environment The present investigations are emphasized on
      generation, characterzation and ecofriendly disposal of solid waste generated in
      Jalgaon city, Maharashtra. In the present study the waste generation at source
      was studied in the various income groups of the city. The per capita waste
      generation was studied by sampling the waste directly from the source of
      generation. The study reveals that the waste generation is large in the high
      income group followed by middle and low-income group public. Further the
      physicochemical characterization of the waste was also studied. The data
      generated will help to develop environmentally sound and economically feasible
      solid waste management system for Ihe city.

PMID- 16459567
TI  - Effect of different irrigation methods on yield of red hot pepper and plant
      mortality caused by Phytophthora capsici Leon.
AB  - This experiment was conducted in 1999 and 2000 in a field naturally infected by
      Phytophthora capsici to determine the effects of different irrigation methods,
      namely, basin (B), closed-end furrow (F), drip (D) and sprinkler (S) irrigation
      on dry yield of chili pepper (Capsium annuum L. K. Maras Type). Water use
      efficiency (WUE) and plant mortality were also measured. The averages of total
      applied water to the B, F, D and S plots for the two years were 937.7 mm, 920.6
      mm, 886.5 and 913.4 mm, respectively. Thus, the mean seasonal water use by pepper
      varied from 1020.7 to 1109.7 mm. The highest water use was measured in B,
      followed by use for S, D and F methods. The highest mean potential dry yield with
      1.58 t ha(-1) was obtained using D method. This was followed by S (1.36 t ha(
      1)), B (1.13 t ha(-1)), and F (0.81 t ha(-1)) methods. In terms of plant
      mortality, crops having B irrigation had the highest (93.9%), followed by lessen
      amount to the S (3.2%), F (3.1%), and D methods (1.7%). Only the B irrigation
      method stimulated the development of P. capsici disease. On the other hand, mean
      WUEs varied between 0.7 and 1.7 kg ha(-1)mnm(-1) for Irrigation methods. WUE for
      D method was slightly higher than S method, but considerably higher than B and F
      methods.

PMID- 16459569
TI  - Influence of pH on lead uptake, chlorophyll and nitrogen content of Nasturtium
      officinale R. Br. and Mentha aquatica L.
AB  - In the present study, effects of pH (5.0, 7.0 and 9.0) and lead (1, 5, 10, 25, 50
      and 100 microg mL(-1)) were investigated on uptake of lead, content of
      chlorophyll and nitrogen in Nasturtium officinale and Mentha aquatica. Total
      chlorophyll and nitrogen contents were adversely affected from Pb2+
      concentrations dose dependently at each pH. The macrophytes were adversely
      affected by pH 5.0 or more than 9.0. After 12-days Pb2+ treatment, results showed
      that lead accumulation of macrophyte tissues was variable. According to the parts
      of the macrophytes, Pb2+ amounts were generally found at all tested pH levels and
      the metal concentrations for M. aquatica in the following order: root > stem >
      leaf and for N. officinale root > leaf > stem. Pb2+ concentrations in plant
      tissues (root, stem, leaf) in relation to pH were generally found for both
      macrophytes in following order: 7.0 > 9.0 > 5.0. Despite of the fact that high
      Pb2+ accumulation was observed in root tissues of the macrophytes, low metal
      accumulation was measured in the above-ground parts indicating low root-leaf
      translocation. The study indicated that uptake rate of Pb2+ and its toxicity on
      Chlorophyll and nitrogen contents in the macrophytes were dependent upon pH value
      of solutions.

PMID- 16459570
TI  - Photoinduced electron storage and surface plasmon modulation in Ag@TiO2 clusters.
AB  - The reversible charging and discharging effects associated with photoexcitation
      of a TiO2 shell in a Ag@TiO2 composite are described. The photoinduced charge
      separation in the TiO2 shell is followed by electron injection into the silver
      core. Interestingly, the charging of the silver core is associated with the shift
      in the surface plasmon band from 460 to 430 nm. The stored electrons are
      discharged upon exposure of the charged Ag@/TiO2 composite to an electron
      acceptor. As the electrons from the silver core are discharged, the original
      surface plasmon absorption of the Ag core is restored.

PMID- 16459572
TI  - Flow-induced patterning of Langmuir monolayers.
AB  - Insoluble monolayers on water have been patterned at the macroscopic scale (i.e.,
      at the centimeter scale of the flow apparatus) as well as the mesoscopic scale
      (i.e., down to the micron scale resolvable via optical microscopy). The
      macroscopic patterning at the air/water interface results from a hydrodynamic
      instability leading to a steadily precessing flow pattern. The velocity field is
      measured, and the associated shear stress at the interface is shown to be locally
      amplified by the flow pattern. The resulting hydrodynamic effects on two
      different monolayer systems are explored: (1) the pattern in a model monolayer
      consisting of micron-size, surface-bound particles is visualized to show that the
      particles are concentrated into isolated regions of converging flow with high
      shear, and (2) Brewster angle microscopy of a Langmuir monolayer (vitamin K1)
      shows not only that the monolayer is patterned at the macroscopic scale but also
      that the localized high-shear flow further patterns the monolayer at the
      mesoscale.

PMID- 16459571
TI  - Large increase in the heat transfer through monolayers detected by beam
      deflection.
AB  - We report the application of photothermal beam deflection for studying heat
      transfer across the liquid/ gas interface covered with surfactant monolayers.
      Laser-induced Marangoni convection was generated on the surface of an absorbing
      aqueous solution with and without a monolayer. The change in heat transfer to the
      air was monitored by the deflection of a probe beam propagating close to the
      solution surface. A large increase in the deflection as well as in the air
      temperature for monolayer-covered surfaces was observed. A film-balance study
      showed that the magnitude of deflection increases as a function of monolayer
      compression.

PMID- 16459574
TI  - Reversible wettability of a chemical vapor deposition prepared ZnO film between
      superhydrophobicity and superhydrophilicity.
AB  - A superhydrophobic ZnO thin film was fabricated by the Au-catalyzed chemical
      vapor deposition method. The surface of the film exhibits hierarchical structure
      with nanostructures on sub-microstructures. The water contact angle (CA) was
      164.3 degrees, turning into a superhydrophilic one (CA < 5 degrees) after UV
      illumination, which can be recovered through being placed in the dark or being
      heated. The film was attached tightly to the substrate, showing good stability
      and durability. The surface structures were characterized by scanning electron
      microscopy and atomic force microscopy.

PMID- 16459573
TI  - Adsorption of Suwannee River fulvic acid on aluminum oxyhydroxide surfaces: an in
      situ ATR-FTIR study.
AB  - The adsorption of Suwannee River fulvic acid (SRFA) on boehmite, gamma-AlO(OH),
      has been examined by both macroscopic adsorption and in situ ATR-FTIR
      spectroscopic techniques. At a SRFA concentration approaching surface saturation
      (F = 5.3 micromol m(-2)), adsorption is at a maximum at low pH and decreases as
      pH is increased. The ATR-FTIR spectral features of adsorbed SRFA are very similar
      to those measured approximately 1-2 pH units higher in solution, indicating that
      (i) the SRFA appears to be predominantly adsorbed at the boehmite/water interface
      in an outer-sphere complexation mode and (ii) the positively charged
      boehmite/water interface stabilizes SRFA molecules against protonation at low pH.

PMID- 16459575
TI  - Depletion potentials induced by charged colloidal rods.
AB  - We present direct depletion potential measurements for a single colloidal sphere
      close to a wall in suspensions of charged colloidal rods. In contrast to earlier
      studies of purely entropic systems (Helden et al. Phys. Rev. Lett. 2003, 90,
      048301), here electrostatic interactions are important. These enhance the
      depletion attraction and lead to repulsive parts in the interaction potentials,
      indicating correlation effects between the rods.

PMID- 16459577
TI  - Uniaxial alignment of the smallest diamagnetic susceptibility axis using time
      dependent magnetic fields.
AB  - A diamagnetic particle with magnetic susceptibilities chi3 < chi2 = chi1 < 0 was
      subjected to a rotating magnetic field to obtain an alignment of the chi3 axis
      (the smallest susceptibility axis) in the direction perpendicular to the plane of
      the rotating magnetic field. A polymer short fiber, whose fiber axis coincides
      with the chi3 axis, was suspended in a fluid with the same density, and then a
      rotating magnetic field generated by a rotation of a pair of permanent magnets
      was applied. The fiber axis, rotating following the applied field, finally ended
      up with an alignment perpendicular to the plane of the rotating magnetic field.
      The experimental data on the time course of the alignment was in good agreement
      with the numerical calculation based on the equation of rotation.

PMID- 16459576
TI  - Partial phase behavior and micellar properties of tetrabutylammonium salts of
      fatty acids: unusual solubility in water and formation of unexpectedly small
      micelles.
AB  - The tetrabutylammonium (TBA) salts of fatty acids, from dodecanoic acid (C12) to
      octacosanoic acid (C28), have been prepared by direct neutralization of the fatty
      acid by TBA hydroxide. Unexpectedly, all of these surfactants have been found to
      be soluble in water under the form of micelles at a sufficiently high
      temperature. For instance, the solubility of TBA octacosanoate in water is of
      about 7 wt % at 46 degrees C. Starting from TBA docosanoate, the aqueous
      solutions of the surfactants gelled below a certain temperature. The gelling
      temperature increased linearly with the fatty acid carbon number. Upon increasing
      temperature, the TBA octocosanoate showed a relatively complex phase behavior
      that has been investigated. The micellar solutions of these surfactants did not
      cloud at high temperatures, up to 98 degrees C, contrary to TBA alkylsulfates.
      The aggregation numbers of micelles of the various TBA alkylcarboxylates have
      been measured and found to be smaller than those for the maximum spherical
      micelle that a surfactant with the same alkyl chain length can form. The micelle
      micropolarity and microviscosity (as sensed by fluorescent probes) decreased and
      increased, respectively, with the fatty acid carbon number.

PMID- 16459578
TI  - Surfactant-free "emulsions" generated by freeze-thaw.
AB  - The stability ofsurfactantless dispersions of surface chemically pure alkanes was
      studied in the presence and absence of dissolved gas. It was found that simply
      freezing and thawing a sample of oil and water results in a dispersion. A
      mechanism based on fingering of the insoluble oil into the aqueous phase, due to
      local surface tension gradients, followed by separation and nucleation into
      droplets, is proposed to account for this observation.

PMID- 16459579
TI  - Effect of hydrophobically modified polymer on salt-induced structural transition
      in microemulsions.
AB  - The phase boundaries of the middle-phase microemulsion for NaCl/SDS/H2O/1
      heptane/1-pentanol systems in the absence of polymer and in the presence of
      unmodified poly(acrylamide) (PAM) and hydrophobically modified poly(acrylamide)
      (HMPAM) have been determined at varying salt concentrations. These three middle
      phase microemulsions (with HMPAM, with PAM, and without polymer) were studied
      using interfacial tension measurement, steady-state fluorescence, and time
      resolved fluorescence quenching. Compared to the polymer-free system and the
      system with PAM, the addition of HMPAM significantly enlarges the range of the
      salt concentrations for the formation of the middle-phase microemulison and
      causes both the excess oil and aqueous phases to increase in volume at the
      expense of the middle-phase microemulsion. For the middle-phase microemulsion
      with HMPAM, the interfacial tensions of the microemulsion phase with the excess
      oil phase and with the excess aqueous phase are all ultralow and exhibit higher
      values than those with PAM and without polymer. At the same salt concentration,
      the apparent surfactant aggregation number in the middle-phase microemulsion with
      HMPAM has the smallest value among these three systems. All results indicate that
      the strong interaction of surfactant with hydrophobically modified polymer has a
      large effect on the formation and properties of the middle-phase microemulsion.

PMID- 16459580
TI  - Thermodynamics of temperature-sensitive polyether-modified poly(acrylic acid)
      microgels.
AB  - The temperature-induced structural changes and thermodynamics of ionic microgels
      based on poly(acrylic acid) (PAA) networks bonded with poly(ethylene oxide)-b
      poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) (Pluronic) copolymers
      have been studied by small-angle neutron scattering (SANS), ultra-small-angle
      neutron scattering (USANS), differential scanning calorimetry (DSC), and
      equilibrium swelling techniques. Aggregation within microgels based on PAA and
      either the hydrophobic Pluronic L92 (average composition, EO8PO52EO8; PPO
      content, 80%) or the hydrophilic Pluronic F127 (average composition,
      EO99PO67EO99; PPO content, 30%) was studied and compared to that in the solutions
      of the parent Pluronic. The neutron scattering results indicate the formation of
      micelle-like aggregates within the F127-based microgel particles, while the L92
      based microgels formed fractal structures of dense nanoparticles. The microgels
      exhibit thermodynamically favorable volume phase transitions within certain
      temperature ranges due to reversible aggregation of the PPO chains, which occurs
      because of hydrophobic associations. The values of the apparent standard enthalpy
      of aggregation in the microgel suspensions indicate aggregation of hydrophobic
      clusters that are more hydrophobic than the un-cross-linked PPO chains in the
      Pluronic. Differences in the PPO content in Pluronics L92 and F127 result in a
      higher hydrophobicity of the resulting L92-PAA-EGDMAmicrogels and a larger
      presence of hydrophobic, densely cross-linked clusters that aggregate into
      supramolecular structures rather than micelle-like aggregates such as those
      formed in the F127-PAA-EGDMA microgels.

PMID- 16459581
TI  - Shear-induced orientation of a rigid surfactant mesophase.
AB  - An optically clear, crystalline, gel-like mesophase is formed by the addition of
      water to a micellar solution consisting of a mixture of 0.85 M anionic surfactant
      sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and a 0.42 M zwitterionic
      surfactant phosphatidylcholine (lecithin) in isooctane. At 25 degrees C and water
      to AOT molar ratio of 70, the system has a columnar hexagonal microstructure with
      randomly oriented domains. The shear-induced orientation and subsequent
      relaxation of this structure were investigated by rheological characterization
      and small-angle neutron scattering (SANS). The rheological response implies that
      the domains align under shear, and remain aligned for several hours after
      cessation of shear. Shear-SANS confirms this picture. The sheared gel mesophase
      retains its alignment as the temperature is increased to 57 degrees C, indicating
      the potential to conduct templated polymer and polymer-ceramic composite
      materials synthesis in aligned systems.

PMID- 16459582
TI  - Structure and aggregation number of a lyotropic liquid crystal: a fluorescence
      quenching and molecular dynamics study.
AB  - The structure and aggregation number of a discotic lyotropic liquid crystal,
      prepared from tetradecyltrimethylammonium chloride (TDTMACl)/decanol
      (DeOH)/NaCl/H2O, have been examined using fluorescence quenching of pyrene by
      hexadecylpyridinium chloride and molecular dynamics (MD). The fluorescence method
      gives an aggregation number of 258 +/- 25 units (DeOH + TDTMACl). From the MD
      simulation, a lower limit for the aggregate dimension of 130 units of DeOH +
      TDTMACl is predicted. A stable oblate aggregate of 240 units was studied in
      detail. A strong polarization between the ammonium headgroups and chloride ions
      is observed from the calculated trajectory. DeOH headgroups are located, on
      average, 0.3 nm more to the interior of the aggregate than the TDTMACl headgroup
      and contribute to widening the interface by forming H-bonds with water. The
      radial distribution function of the ammonium headgroup shows that there are 16
      water molecules in the first solvation sphere. The diagonal elements of the order
      parameter tensor of the tail atoms of both surfactants indicate that the interior
      of the micelle preserves about the same degree of order as at the interface, up
      to the last three atoms of the aliphatic chain, where the order starts to
      decrease.

PMID- 16459583
TI  - Characterization of supported solid thin films of Laponite clay. Intercalation of
      rhodamine 6G laser dye.
AB  - The morphology of thin films of Laponite (Lap) clay elaborated by the evaporation
      method and spin-coating technique was analyzed by atomic force microscopy and
      scanning electron microscopy, indicating a better quality film for the latter
      procedure. Rhodamine 6G (R6G) laser dye was intercalated into these films by ion
      exchange mechanism, performed by immersing the clay film into adequate dye
      solutions in which the effect of the dye concentration, immersion time, and
      nature of the solvent on the adsorption process were checked. The adsorption of
      R6G at the interlayer space of Lap was analyzed by the X-ray diffraction
      technique, and the presence of several R6G species (monomers and aggregates) was
      characterized by absorption and fluorescence spectroscopies. Less viscous
      solvents lead to higher dye loadings, suggesting a diffusional process for the
      intercalation of the dye in the interlayer spaces of Lap, and polar solvents
      favor the swellability of the interlayer space giving rise to a more homogeneous
      distribution of R6G molecules through the film and decreasing the dye
      aggregation. With the aging of the samples, the dye molecules can migrate through
      the interlayer spaces, leading to a more expanded distribution of R6G molecules
      and to the dye deaggregation.

PMID- 16459584
TI  - Preparation of J-aggregate liposome dispersions and their chromic transformation.
AB  - We report the preparation of aqueous liposome dispersions of J-aggregates formed
      by the amphiphilic merocyanine dye (MD). A series of liposome-forming lipids were
      dispersed together with MD J-aggregates at different molar ratios of MD to lipid.
      The MD J-aggregate dispersions prepared with 1,2-dimyristoyl-sn-glycero-3
      phosphocholine (DMPC) at the MD to DMPC ratio of 0.16 exhibit good
      dispersibility; that is, they can be readily redispersed without any flocculation
      even after their precipitation. By use of different counterions for the MD
      molecules, two types of J-aggregate dispersions, one that exhibits an absorption
      band (J-band) at 635 nm (type I) and the other at 600 nm (type II), were
      obtained. As an example of the use of MD J-aggregates liposome dispersions, the
      thermochromic transformation of MD J-aggregates was demonstrated. When the
      dispersions are heated, J-aggregates of type I transformed into type II at a
      certain temperature (T(disp)). The parameters that control the speed of the
      transformation and the value of T(disp) were determined.

PMID- 16459585
TI  - Macroscopic model of phospholipid vesicle spreading and rupture.
AB  - We present a macroscopic model for the spreading and rupture of a spherical lipid
      vesicle on a flat, isotropic, hydrophilic surface. Formulas for the free energy
      of the initial and final states are derived, and the details of spreading
      pathways are examined. We show that the activation barrier for vesicle rupture is
      too large to be overcome by thermal fluctuations at room temperature and the
      final configuration is more likely to consist of a deflated vesicle. In order for
      the vesicle to rupture into a planar bilayer, it would have to be aided by
      increased temperature, application of an external force, or preparation of a
      mixed hydrophilic/ hydrophobic surface.

PMID- 16459586
TI  - Effect of the addition of a nonaqueous polar solvent (glycerol) on enzymatic
      catalysis in reverse micelles. Hydrolysis of 2-naphthyl acetate by alpha
      chymotrypsin.
AB  - The kinetics of hydrolysis of 2-naphthyl acetate (2-NA) catalyzed by alpha
      chymotrypsin (alpha-CT), in reverse micellar solutions formed by glycerol (GY)
      water (38% v/v) mixture/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/n-heptane
      has been determined by spectroscopic measurements. To compare the efficiency of
      this reaction with that observed in micelles with water in the core, as well as
      in the corresponding homogeneous media, the reaction was also studied in
      water/AOT/n-heptane reverse micellar solutions and in both homogeneous media
      (water and GY-water, 38% v/v mixture). In every media, alpha-CT was characterized
      by the absorption and emission spectra, the fluorescence lifetimes, and the
      fluorescence anisotropy of its tryptophan residues. The effect of AOT
      concentration on the kinetic parameters obtained in the micellar systems was
      determined, at a constant molar ratio of the inner polar solvent and surfactant.
      Moreover, the data obtained allowed the evaluation of the 2-NA partition constant
      between the organic and the micellar pseudophase. It is shown that the addition
      of GY to the micelle interior results in an increase in the catalytic properties
      of alpha-CT. The fluorescence anisotropy studies in the different media show that
      the addition of GY increases the viscosity as compared with the aqueous systems.
      It seems that the GY addition to the reverse micellar aggregates results in a
      decrease of the conformational mobility of alpha-CT, which leads to an increase
      of the enzyme stability and activity.

PMID- 16459587
TI  - Automated high-performance purification of surfactant solutions: study of
      convective-enhanced adsorption.
AB  - Due to the amphiphilic nature of surfactants, they generally contain traces of
      their more surface-active parent components irrespective of the as received
      surfactant's label declaration. These trace impurities are preferentially
      enriched in the surfactant's adsorbed layer. To attain the state of "surface
      chemical purity" that implies the absence of impurities in the adsorbed layer, we
      had developed an automatic high-performance purification apparatus years ago.
      Here we put forward an improved version of this successful technique that
      considerably reduces the time required to purify surfactant solutions by
      accelerating the adsorption through convection. The advantages and reliability of
      the new technique are demonstrated by the purification characteristics of
      different solutions of as-received surfactants of varying degree of purity. As
      the overall time gained with convective purification is of 1 order of magnitude,
      the improved technique is particularly favorable for surfactant solutions that
      are prone to hydrolysis or degradation.

PMID- 16459588
TI  - Mixed micelles formed by n-octyl-beta-D-glucopyranoside and
      tetradecyltrimethylammonium bromide in aqueous media.
AB  - Speed of sound, density, conductivity, and fluorescence spectroscopy experiments
      were run to analyze the mixed aggregation process of a nonionic-cationic
      surfactant system in aqueous media at 298.15 K. The mixed system comprises a
      nonionic surfactant, n-octyl-beta-D-glucopyranoside (OBG), and a cationic
      surfactant, tetradecyltrimethylammonium bromide (C14TAB), with 8 and 14 carbon
      atoms on the hydrophobic tails, respectively. From these data, the total and
      partial critical micellar concentrations, the total and partial aggregation
      numbers, apparent molar volumes and isentropic compressibilities, hydration
      numbers, and the corresponding changes in the latest properties due to the mixed
      aggregation process were determined. Pure and mixed micelles were analyzed from a
      geometrical point of view by determining the packing parameter of the aggregates.
      Furthermore, the experimental characterization of both the monomeric and micellar
      phases was completed with a theoretical study of the mixed micellization
      phenomena studied herein, by means of some of the most relevant theoretical
      models.

PMID- 16459589
TI  - Comparison of droplet flocculation in hexadecane oil-in-water emulsions
      stabilized by beta-lactoglobulin at pH 3 and 7.
AB  - The influence of surface and thermal denaturation of adsorbed beta-lactoglobulin
      (beta-Lg) on the flocculation of hydrocarbon oil droplets was measured at pH 3
      and compared with that at pH 7. Oil-in-water emulsions (5 wt % n-hexadecane, 0.5
      wt % beta-Lg, pH 3.0) were prepared that contained different levels of salt (0
      150 mM NaCl) added immediately after homogenization. The mean particle diameter
      (d43) and particle size distribution of diluted emulsions were measured by laser
      diffraction when they were either (i) stored at 30 degrees C for 48 h or (ii)
      subjected to different thermal treatments (30-95 degrees C for 20 min). In the
      absence of salt, little droplet flocculation was observed at pH 3 or 7 because of
      the strong electrostatic repulsion between the droplets. In the presence of 150
      mM NaCl, a progressive increase in mean particle size with time was observed in
      pH 7 emulsions during storage at 30 degrees C, but no significant change in mean
      particle diameter with time (d43 approximately 1.4 +/- 0.2 microm) was observed
      in the pH 3 emulsions. Droplet aggregation became more extensive in pH 7
      emulsions containing salt (added before thermal processing) when they were heated
      above 70 degrees C, which was attributed to thermal denaturation of adsorbed beta
      Lg leading to interdroplet disulfide bond formation. In contrast, the mean
      particle size decreased and the creaming stability improved when pH 3 emulsions
      were heated above 70 degrees C. These results suggest that the droplets in the pH
      3 emulsions were weakly flocculated at temperatures below the thermal
      denaturation temperature of beta-Lg (T < 70 degrees C) but that flocs did not
      form so readily above this temperature, which was attributed to a reduction in
      droplet surface hydrophobicity due to protein conformational changes. The most
      likely explanation for the difference in behavior of the emulsions is that
      disulfide bond formation occurs much more readily at pH 7 than at pH 3.

PMID- 16459590
TI  - Study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed
      micelles.
AB  - Sodium dodecyl sulfate (SDS)-poly(propylene oxide) methacrylate (PPOMA) (of
      molecular weight M(w) = 434 g x mol(-1)) mixtures have been studied using
      conductimetry, static light scattering, fluorescence spectroscopy, and 1H NMR. It
      has been shown that SDS and PPOMA form mixed micelles, and SDS and PPOMA
      aggregation numbers, N(ag SDS) and N(ag PPOMA), have been determined. Total
      aggregation numbers of the micelles (N(ag SDS) + N(ag PPOMA)) and those of SDS
      decrease upon increasing the weight ratio R = PPOMA/SDS. Localization of PPOMA
      inside the mixed micelles is considered (i) using 1H NMR to localize the
      methacrylate function at the hydrophobic core-water interface and (ii) by
      studying the SDS-PPO micellar system (whose M(w) = 400 g x mol(-1)). Both methods
      have indicated that the PPO chain of the macromonomer is localized at the SDS
      micelle surface. Models based on the theorical prediction of the critical
      micellar concentration of mixed micelles and structural model of swollen micelles
      are used to confirm the particular structure proposed for the SDS-PPOMA system,
      i.e., the micelle hydrophobic core is primarily composed of the C12 chains of the
      sodium dodecyl sulfate, the hydrophobic core-water interface is made up of the
      SDS polar heads as well as methacrylate functions of the PPOMA, the PPO chains of
      the macromonomer are adsorbed preferentially on the surface, i.e., on the polar
      heads of the SDS.

PMID- 16459591
TI  - Transition from mushroom to brush during formation of a tethered layer.
AB  - Tethering of monodisperse, chain-end-functionalized polymer from dilute solution
      to a solid surface shows three regimes of kinetics. This paper presents support
      for the hypothesis that the experimentally observed third regime is indeed the
      transition from mushroom to brush and that it occurs in a spatially nonuniform
      manner. Both time-step snapshots generated by a Monte Carlo simulation of the
      tethering process and atomic force microscopy images of actual surfaces during
      the process show that the third regime is characterized by nonuniform surface
      texture, while the surface texture is uniform prior to and after the third
      regime.

PMID- 16459593
TI  - Thermal chemistry of cis-1,2-dichloroethene on Pd(111).
AB  - The reaction of cis-1,2-dichloroethene (cis-DCE) on Pd(111) has been investigated
      by temperature-programmed desorption, laser-induced thermal desorption, Auger
      electron spectroscopy, and Fourier transform reflection absorption infrared
      spectroscopy. Below 130 K, molecularcis-DCE aggregates, resulting in only about
      30% of the molecules from exposures below saturation significantly interacting
      with the palladium surface. The decomposition of cis-DCE generates the observable
      species H2, HCl, and ethylidyne. A fraction of cis-DCE molecules lose both
      chlorine atoms and add hydrogen to form ethylidyne, which is stable on the
      surface between 250 and 370 K. Hydrogen is liberated at about 420 K from cis-DCE
      surface fragments that immediately combine with surface chlorine and desorb as
      HCl. The most intense HCl desorption occurs at about 575 K and is due to surface
      chlorine reacting with either subsurface hydrogen or hydrogen from the remaining
      surface alkyl fragments. No carbon-containing species desorb from the
      decomposition of cis-DCE.

PMID- 16459594
TI  - Molecular simulation evidence for solidlike adsorbate in complex carbonaceous
      micropore structures.
AB  - Adsorption of a model nitrogen vapor on a range of complex nanoporous carbon
      structures is simulated by grand canonical Monte Carlo simulation for a single
      subcritical temperature above the bulk freezing point. Adsorption and desorption
      isotherms, heats of adsorption, and three-dimensional singlet distribution
      functions (SDFs) were generated. Inspection of the SDFs reveals significant
      levels of solidlike adsorbate at saturation even in the most complex of the
      microporous solids considered. This strongly suggests that solidlike adsorbate
      will also occur for simple subcritical vapors adsorbed on real noncrystalline
      solids such as microporous carbons at temperatures above the bulk freezing point,
      supporting indirect experimental observations. The presence of significant levels
      of solidlike adsorbate has implications for characterization of microporous
      solids where adsorbate density is used (e.g., determination of pore volume from
      loading). Detailed consideration of the SDF at different loadings for a model
      microporous solid indicates solidlike adsorbate forms at distributed points
      throughout the pore space at pressures dependent on the nature of the local
      porosity. The nature of the local porosity also dictates the freezing mechanism.
      A local freezing/ melting/refreezing process is also observed. Introduction of
      mesoporosity into the model causes hysteresis between the adsorption and
      desorption isotherms. Adsorption in the hysteresis loop occurs by a series of
      local condensation events. It appears as if the presence of adjacent
      microporosity and/or adsorbate within it affects the pressure at which these
      events occur. Reversal of the condensation during desorption occurs throughout
      the mesoporosity at a single pressure; this pressure is unaffected by the
      presence of adjacent microporosity or the adsorbate within it. It is also shown
      that the empirical concept of "pore size" is not consistent for describing
      adsorption in the complex solids considered here. A new concept is, therefore,
      proposed that seeks to account for the factors that affect local adsorption
      energy: local geometry, microtexture, surface atom density, and surface
      chemistry.

PMID- 16459592
TI  - Self-assembled organic monolayers terminated in perfluoroalkyl pentafluoro
      lambda(6)-sulfanyl (-SF5) chemistry on gold.
AB  - Recently synthesized (Winter, R.; Nixon, P. G.; Gard, G. L.; Radford, D. H.;
      Holcomb, N. R.; Grainger, D. W. J. Fluorine Chem. 2001, 107, 23-30) SF5
      terminated perfluoroalkyl thiols (SF5(CF2)nCH2CH2SH, where n = 2, 4, and 6) and a
      symmetric SF5-terminated dialkyl disulfide ([SF5-CH=CH-(CH2)8-S-]2) were
      assembled as thin films chemisorbed onto gold surfaces. The adsorbed monolayer
      films of these SF5-containing molecules on polycrystalline gold were compared
      using ellipsometry, contact angle, X-ray photoelectron spectroscopy (XPS), time
      of-flight secondary ion mass spectrometry (ToF-SIMS), and infrared spectroscopy
      (FTIR) surface analytical methods. The resulting SF5-dialkyl disulfide monolayer
      film shows moderate angle dependence in depth-dependent XPS analysis, suggesting
      a preferentially oriented film. The SF5-terminated perfluoroalkyl thiols exhibit
      angular-dependent XPS compositional variance depending on perfluoroalkyl chain
      length, consistent with improved film assembly (increasingly hydrophobic, fewer
      defects, and more vertical chain orientation increasing film thickness) with
      increasing chain length. Tof-SIMS measurements indicate that both full parent
      ions for these film-forming molecules and the unique SF5 terminal group are
      readily detectable from the thin films without substantial contamination from
      other adsorbates.

PMID- 16459595
TI  - Electron paramagnetic resonance studies of magnetically aligned phospholipid
      bilayers utilizing a phospholipid spin label.
AB  - X-band electron paramagnetic resonance (EPR) spectroscopy was used to study the
      structural and dynamic properties of magnetically aligned phospholipid bilayers
      utilizing a variety of phosphocholine spin labels (PCSL) as a function
      oftemperature. 1-Palmitoyl-2-[n-(4,4-dimethyloxazolidine-N-oxyl)stearoyl]-sn
      glycero-3-phosphocholine (n-PCSL) in which a nitroxide group was attached to the
      different acyl chain positions of the phospholipid (n = 5, 7, 12, and 14) were
      used as an EPR spin probe to investigate magnetically aligned phospholipid
      bilayers from the plateau (near to the headgroup) region to the end of the acyl
      chain (center of the bilayers). The addition of certain types of paramagnetic
      lanthanide ions changes the overall magnetic susceptibility anisotropy tensor of
      the bicelles, such that the bicelles flip with their bilayer normal either
      parallel or perpendicular to the magnetic field. The present study reveals for
      the first time that, in the case of the n-PCSL, the bilayer normal is aligned
      parallel and perpendicular to the magnetic field in the presence of lanthanide
      ions having positive delta(chi) (e.g., Tm3+) and negative delta(chi) (e.g.,
      Dy3+), respectively. The magnetic alignment of the bilayers and the corresponding
      segmental molecular order parameter, S(mol), were investigated as a function of
      the temperature. The S(mol) values decrease in the following order, 5-PCSL > 7
      PCSL > 12-PCSL > 14-PCSL, for the magnetically aligned phospholipid bilayers.
      Also, the variable temperature study indicates that, by increasing the
      temperature, the order parameters S(mol) decreased for all the n-PCSLs. The
      results indicate that magnetically aligned phospholipid bilayers represent an
      excellent model membrane system for X-band EPR studies.

PMID- 16459596
TI  - Langmuir and Langmuir-Blodgett films of amphiphilic bistable rotaxanes.
AB  - A series of amphiphilic bistable [2]rotaxanes--in which a ring-shaped component,
      the tetracationic cyclophane, cyclobis(paraquat-p-phenylene), has been assembled
      around two recognition sites, a tetrathia-fulvalene (TTF) unit and a 1,5
      dioxynaphthalene (DNP) ring system, situated apart at different strategic
      locations within the central polyether section of an amphiphilic dumbbell
      component that is terminated by a hydrophobic tetraarylmethane-based stopper
      (near the TTF unit) at one end and by a hydrophilic tetraarylmethane-based
      stopper (near the DNP ring system) at the other end--has been designed and
      synthesized. The effects of systematic changes in the constitutions of the three
      ethylene glycol tails (diethylene or tetraethylene glycol) and end groups
      (hydroxyl or methoxyl functions) attached to the hydrophilic stoppers on Langmuir
      film balance and surface rheology experiments at 20 degreesC were examined to
      determine the monolayer stabilities and co-conformations of the [2] rotaxanes and
      their free dumbbell counterparts. These experiments allow us to propose a model
      for the rotaxane's structures at different surface pressures. All the
      [2]rotaxanes form stable Langmuir films. These films typically pass from a liquid
      expanded region to a liquid-condensed region. The transition between the two
      regions was either directly observed or ascertained using film stability
      experiments. Film balance and surface rheology experiments showed that the
      addition of the tetracationic cyclophane component and hydroxyl end groups
      markedly increased the stabilities and viscoelasticity of the films.

PMID- 16459597
TI  - Loosely packed self-assembled monolayers on gold generated from 2-alkyl-2
      methylpropane-1,3-dithiols.
AB  - A series of 2-alkyl-2-methylpropane-1,3-dithiol derivatives with increasing alkyl
      chain lengths (i.e., CH3(CH2)mC(CH3)[CH2SH]2, where m = 7, 9, 11, 13, 15) were
      synthesized and used to generate self-assembled monolayers (SAMs) on gold. The
      resulting monolayers were analyzed by ellipsometry, contact angle goniometry,
      polarization modulation infrared reflection-absorption spectroscopy, and X-ray
      photoelectron spectroscopy. These data were compared with those obtained on SAMs
      on gold derived from normal alkanethiols (CH3(CH2)(m+2)SH) and 2-monoalkylpropane
      1,3-dithiols (CH3(CH2)(m)CH[CH2SH]2) having the same number of carbon atoms in
      the primary chain. The results demonstrate that the 2-alkyl-2-methylpropane-1,3
      dithiols generate conformationally disordered monolayer films in which the
      density of alkyl chains is less than those generated from normal alkanethiols and
      the 2-monoalkylpropane-1,3-dithiols.

PMID- 16459598
TI  - Using the adhesive interaction between atomic force microscopy tips and polymer
      surfaces to measure the elastic modulus of compliant samples.
AB  - An atomic force microscope (AFM) method for measuring surface elasticity based on
      the adhesive interactions between an AFM tip and sample surfaces is introduced.
      The method is particularly useful when there is a large adhesion between the tip
      and soft samples, when the indentation method would be less accurate. For thin
      and soft samples, this method will have much less interference from the substrate
      than is found using the indentation method because there is only passive
      indentation induced by tip-sample adhesion; in contrast, a large indentation with
      a sharp tip in the sample may break its stress-strain linearity, or even make it
      fracture. For the case where it is difficult to accurately locate the tip-sample
      contact point, which is problematic for the indentation method, the method based
      on adhesive interactions is helpful because it does not require locating the tip
      sample contact point when fitting the whole retraction force curve. The model is
      tested on PDMS polymers with different degrees of cross-linking.

PMID- 16459599
TI  - Photochemical modification of diamond films: introduction of perfluorooctyl
      functional groups on their surface.
AB  - Photolysis of perfluoroazooctane with diamond films led the chemical modification
      of the surface to introduce perfluorooctyl functional groups, confirmed by means
      of Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy
      (XPS), Raman spectroscopy, and time-of-flight secondary ion mass spectrometry
      measurements. Diamond films modified with fluorine moieties showed improved
      frictional property and reduction of surface energy, as evaluated by contact
      angle to water, compared with a pristine diamond film. The contact angle and
      friction coefficient of chemically modified diamond film are 118 degrees and 0.1,
      respectively. The results of the value of the contact angle depending on
      irradiation times are consistent with those of the F/C ratio of fluorinated
      diamond films by monitoring with XPS.

PMID- 16459601
TI  - Citrate-reduced silver hydrosol modified with omega-mercaptoalkanoic acids self
      assembled monolayers as a substrate for surface-enhanced resonance Raman
      scattering. A study with cytochrome c.
AB  - A new citrate-reduced silver hydrosol coated with omega-mercaptoalkanoic acids
      (mercaptopropionic and mercaptoundecanoic acids) self-assembled monolayers was
      prepared and characterized with surface-enhanced Raman spectroscopy. The
      structure and the quality of the coating monolayers are discussed and compared to
      similar coated and uncoated silver hydrosols previously developed. As an
      application, the new hydrosol was used as a biocompatible and efficient metal
      substrate for a surface-enhanced resonance Raman scattering (SERRS) study of
      cytochrome c. The high-quality SERRS spectra reported of cytochrome c (obtained
      using only 1 microL of a micromolar cytochrome solution) are discussed and
      compared with data available from literature studies.

PMID- 16459600
TI  - An evanescent-field-driven self-assembled molecular photoswitch for macrocycle
      coordination and release.
AB  - Two self-assembled monolayer (SAM) films containing the photoswitchable 4
      pyridylazophenoxy chromophore have been deposited onto a gold-coated glass
      substrate. One film contains the chromophore as a single component, 1 SAM, and
      the other is doped with a nonphotoactive component as a 1:1 mixture, 2 SAM. The
      reversible photoswitching performances of 1 SAM and 2 SAM via the evanescence
      field using light of appropriate wavelengths have been investigated by UV
      spectroscopic and electrochemical monitoring. In principle, the trans-form SAMs
      present a coordinating surface, the "on" state, that can be switched "off" in the
      cis form. This has been illustrated by immersing both the as-deposited (trans
      form) SAMs and the photoswitched (predominantly cis form) SAMs into solutions of
      cobalt and zinc tetraphenylporphyrin (CoTPP and ZnTPP, respectively) and an
      octaoctyl-substituted cobalt phthalocyanine. In a further phase of this study,
      the remote control of binding events at the surface of the SAMs has been
      demonstrated through evanescent-field-driven photoswitching of trans-form SAMs
      coordinated at the surfaces with examples of these metallomacrocycles. This
      photoswitching was undertaken with the constructs immersed in neat toluene, and
      the macrocycles were released from the surface into the solvent. The release was
      measured by spectroscopic monitoring of the material remaining on the constructs.
      The study was extended to develop an in situ release/coordination cycle. Thus,
      irradiation of a construct of ZnTPP bound to the surface of trans-form 2 SAM
      using waveguided light at 365 nm releases the macrocycle into a toluene solution
      of ZnTPP. Further irradiation of the SAM, now in its cis form, with waveguided
      439 nm light regenerates the trans form, which recoordinates ZnTPP from the
      solution. The results demonstrate the potential for using waveguided light to
      control molecular events within and at the surfaces of SAM constructs.

PMID- 16459602
TI  - Preparation and photocatalytic behavior of MoS2 and WS2 nanocluster sensitized
      TiO2.
AB  - A new approach has been developed for the fabrication of visible light
      photocatalysts. Nanoclusters of MoS2 and WS2 are coupled to TiO2 by an in situ
      photoreduction deposition method taking advantage of the reducing power of the
      photogenerated electrons from TiO2 particles. The photocatalytic degradation of
      methylene blue and 4-chlorophenol in aqueous suspension has been employed to
      evaluate the visible light photocatalytic activity of the powders. The blue shift
      in the absorption onset confirms the size quantization of MS2 nanoclusters, which
      act as effective and stable sensitizers, making it possible to utilize visible
      light in photocatalysis. Quantum size effects alter the energy levels of the
      conduction and valence band edges in the coupled semiconductor systems, which
      favors the interparticle electron transfer. In addition, the coupled systems are
      believed to act in a cooperative manner by increasing the degree of charge
      carrier separation, which effectively reduces recombination.

PMID- 16459604
TI  - Adsorption and immobilization of cytochrome c on nanodiamonds.
AB  - Methods have been developed to immobilize proteins onto the surfaces
      ofnanodiamonds with an average size of 5 +/- 1 nm. The immobilization started
      with carboxylation/oxidization of diamonds with strong acids, followed by coating
      the surfaces with poly-L-lysine (PL) for covalent attachment of proteins using
      heterobifunctional cross-linkers. The feasibility of this approach is proven with
      fluorescent labeling of the PL-coated diamonds by Alexa Fluor 488 and subsequent
      detection of the emission using a confocal fluorescence microscope.
      Immobilization of proteins onto the surfaces is also demonstrated with yeast
      cytochrome c, which possesses a free SH group for linkage and a characteristic
      Soret absorption band for observation.

PMID- 16459603
TI  - Human immunoglobulin adsorption investigated by means of quartz crystal
      microbalance dissipation, atomic force microscopy, surface acoustic wave, and
      surface plasmon resonance techniques.
AB  - Time-resolved adsorption behavior of a human immunoglobin G (hIgG) protein on a
      hydrophobized gold surface is investigated using multitechniques: quartz crystal
      microbalance/dissipation (QCM-D) technique; combined surface plasmon resonance
      (SPR) and Love mode surface acoustic wave (SAW) technique; combined QCM-D and
      atomic force microscopy (AFM) technique. The adsorbed hIgG forms interfacial
      structures varying in organization from a submonolayer to a multilayer. An "end
      on" IgG orientation in the monolayer film, associated with the surface coverage
      results, does not corroborate with the effective protein thickness determined
      from SPR/SAW measurements. This inconsistence is interpreted by a deformation
      effect induced by conformation change. This conformation change is confirmed by
      QCM-D measurement. Combined SPR/SAW measurements suggest that the adsorbed
      protein barely contains water after extended contact with the hydrophobic
      surface. This limited interfacial hydration also contributed to a continuous
      conformation change in the adsorbed protein layer. The viscoelastic variation
      associated with interfacial conformation changes induces about 1.5 times
      overestimation of the mass uptake in the QCM-D measurements. The merit of
      combined multitechnique measurements is demonstrated.

PMID- 16459605
TI  - Oriented binding of the His6-tagged carboxyl-tail of the L-type Ca2+ channel
      alpha1-subunit to a new NTA-functionalized self-assembled monolayer.
AB  - Oriented stable binding of functional proteins on surfaces is of fundamental
      interest for receptor/ligand studies in atomic force microscopy (AFM) and surface
      plasmon resonance (SPR) experiments. Here we have chosen the His6-tagged carboxyl
      tail (C-tail) of the alpha1c-subunit of the L-type Ca2+ channel and calmodulin
      (CaM) as its cognitive partner as a model system to develop a new functional
      surface. Covalently attached self-assembled monolayers on ultraflat gold
      containing NTA-thiols to which the His6-tagged C-tail was bound and thiols with
      triethylene-glycol groups as matrix-thiols represented the system of choice. The
      topography of this surface was characterized using AFM; its ability to bind C
      tail proteins oriented and stable was confirmed by SPR measurements and by
      complementary force spectroscopy experiments with a CaM4-construct covalently
      attached to the tip. The developed anchoring strategy can now be used to study
      receptor/ligand interactions in general applying force spectroscopy and SPR on
      His6-tagged proteins oriented immobilized onto this new NTA-functionalized self
      assembled monolayer.

PMID- 16459606
TI  - Formation of a DNA layer on Langmuir-Blodgett films and its enzymatic digestion.
AB  - Here, we report a system we have developed where long double-stranded DNAs
      (dsDNAs) are immobilized on a monolayer of Zn-arachidate. We have applied the
      Langmuir-Blodgett technique to form the monolayer of Zn-arachidate where Zn(II)
      is bound to arachidic acid through charge neutralization. Because tetrahedral
      Zn(II) participates in DNA recognition through coordination, we have been able to
      layer DNA over the Zn-arachidate monolayer. The DNA layer shows a typical
      compression and expansion cycle in a concentration-dependent fashion.
      Interestingly, the DNA monolayer is available for enzymatic degradation by
      DNaseI. The detection of DNA and its accessibility towards biological reaction is
      demonstrated by imaging through fluorescence microscopy. The conformation of the
      DNA, immobilized on the monolayer, was studied with the help of atomic force
      microscopy (AFM). We observed that the dsDNAs were aligned in a stretched manner
      on the surface. To investigate further, we also demonstrate here that the small
      single-stranded DNA (ssDNA) immobilized on the air-water interface can act as a
      target molecule for the complementary ssDNA present in the subphase. The study of
      DNA hybridization done with the help of fluorescence spectroscopy clearly
      supports the AFM characterization.

PMID- 16459608
TI  - Immobilization of DNA onto poly(dimethylsiloxane) surfaces and application to a
      microelectrochemical enzyme-amplified DNA hybridization assay.
AB  - This paper describes immobilization of DNA onto the interior walls of
      poly(dimethylsiloxane) (PDMS) microsystems and its application to an enzyme
      amplified electrochemical DNA assay. DNA immobilization was carried out by
      silanization of the PDMS surface with 3-mercaptopropyltrimethoxysilane to yield a
      thiol-terminated surface. 5'-acrylamide-modified DNA reacts with the pendant
      thiol groups to yield DNA-modified PDMS. Surface-immobilized DNA oligos serve as
      capture probes for target DNA. Biotin-labeled target DNA hybridizes to the PDMS
      immobilized capture DNA, and subsequent introduction of alkaline phosphatase (AP)
      conjugated to streptavidin results in attachment of the enzyme to hybridized DNA.
      Electrochemical detection of DNA hybridization benefits from enzyme
      amplification. Specifically, AP converts electroinactive p-aminophenyl phosphate
      to electroactive p-aminophenol, which is detected using an indium tin oxide
      interdigitated array (IDA) electrode. The IDA electrode eliminates the need for a
      reference electrode and provides a steady-state current that is related to the
      concentration of hybridized DNA. At present, the limit of detection of the DNA
      target is 1 nM in a volume of 20 nL, which corresponds to 20 attomoles of DNA.

PMID- 16459607
TI  - Amphiphilic 4-helix bundles designed for biomolecular materials applications.
AB  - Artificial peptides previously designed to possess alpha-helical bundle motifs
      have been either hydrophilic (i.e., soluble in polar media) or lipophilic (i.e.,
      soluble in nonpolar media) in overall character. Realizations of these
      bioinspired bundles have succeeded in reproducing a variety of biomimetic
      functionality within the appropriate media. However, to translate their
      functionality into any biomolecular device applications at the macroscopic level,
      the bundles must be oriented in an ensemble, for example, at an interface. This
      goal has been realized in a new family of alpha-helical bundle peptides which are
      amphiphilic; namely, they assemble into 4-helix bundles with well-defined
      hydrophilic and hydrophobic domains. These peptides are capable of binding
      metalloporphyrin prosthetic groups at selected locations within these domains. We
      describe here the realization of one of the first members of this family, AP0,
      successfully designed for vectorial incorporation into soft interfaces between
      polar and nonpolar media.

PMID- 16459609
TI  - Narrow-band irradiation of a homologous series of chlorophenols on TiO2: charge
      transfer complex formation and reactivity.
AB  - The goal of this research was to investigate the formation and reactivity of
      charge-transfer complexes (CTCs) among a homologous series of chlorophenols on
      TiO2. We previously showed that 2,4,5-trichlorophenol (245TCP) forms a CTC with
      Degussa P25, a commercial preparation of TiO2. Here, we probe how light energy
      influences reactivity and product formation. Slurries of P25 containing 245TCP
      were irradiated at 360, 400, 430, 480, and 550 nm. At each wavelength, the amount
      of transformation of 245TCP correlates to the diffuse-reflectance absorbance of a
      245TCP/P25 system, supporting the CTC as the cause of reaction. In addition,
      polymeric products are formed only under wavelengths that excite the CTC,
      indicating a different reaction mechanism for the CTC than for bandgap excitation
      of TiO2. We also found a higher quantum efficiency for CTC reactivity than for
      bandgap activation of the catalyst, suggesting that the photocatalytic efficiency
      and selectivity can be improved for certain compounds by designing catalytic
      materials that form CTCs with them. Furthermore, to determine how chlorine
      substitution patterns affected adsorption and sub-bandgap reactivity, P25
      slurries containing phenol, 4-chlorophenol, 2,4-dichlorophenol, or 2,4,6
      trichlorophenol were probed following dark contact or irradiation at 360, 430, or
      550 nm. With respect to the extent of adsorption, complexation, reaction, and
      polymerization on P25, the behavior of 245TCP far exceeded that of the other
      chlorophenols. Among these chlorophenols, only 2,4-dichlorophenol produced a
      polymeric product. 245TCP is unique among this family of chlorophenols, which we
      attribute to a chlorine arrangement that leads to a favorable orbital overlap
      with TiO2 and sterically permits coupling reactions. Our results demonstrate the
      critical role that charge-transfer complexation can play in determining the rates
      and products of photocatalytic reactions.

PMID- 16459610
TI  - Aggregation of photolytic gold nanoparticles at the surface of chitosan films.
AB  - Formation and aggregation of photolytic gold nanoparticles at the surface of
      chitosan (CTO) films have been investigated. When thin films of chloroauric acid
      salt of CTO were irradiated with UV light in wet air at room temperature for 10
      min, gold nanoparticles of approximately 10 nm size are formed at the film
      surface. Detailed X-ray photoelectron spectroscopy (XPS) study and field emission
      type scanning electron microscopy (FE-SEM) observation have been carried out to
      characterize gold nanoparticles at the film surface. The shift of Au(4f) peak to
      the higher energy side and broadening of full width at half-maximum in the XPS
      spectrum are the direct evidence of the existence of gold atoms and small
      clusters in the early stage of photolysis. According to FE-SEM observation,
      growth in the particle diameter and aggregation of nanoparticles were observed
      after prolonged irradiation, and, finally, the film surface was densely covered
      with gold particles of 20-100-nm size. Gold atoms and clusters could move in the
      film and precipitate to the irradiated surface. Chemical composition analysis
      further suggests that gold particles at the surface are covered with an ultrathin
      CTO layer, which is partly oxidized by oxygen and chlorinated by chlorine during
      photochemical reactions.

PMID- 16459611
TI  - Evaluating formation and growth mechanisms of silica particles using fluorescence
      anisotropy decay analysis.
AB  - At present, there is no direct experimental evidence that primary silica
      particles, which exist only transiently for a few seconds during the Stober
      silica synthesis, can be stable in aqueous solutions. In the present work, we
      show that primary silica particles are formed spontaneously after the dissolution
      of diglycerylsilane (DGS) in aqueous solutions and remain stable for prolonged
      periods of time. By using time-resolved fluorescence anisotropy (TRFA), we
      demonstrate that this unique property of DGS is ascribed to the slow kinetics of
      silica particle growth in diluted sols at pH approximately 9.0. The anisotropy
      decay of the cationic dye rhodamine 6G (R6G), which strongly adsorbs to silica
      oligomers and nanoparticles in DGS sols, could be fit to three components: a fast
      (picosecond) scale component associated with free R6G, a slower (nanosecond)
      rotational component associated with R6G bound to primary silica particles, and a
      residual (nondecaying) anisotropy component associated with R6G that was bound to
      secondary or larger particles that were unable to rotate on the time scale of the
      R6G emission lifetime (4 ns). The data show that, under conditions where fast
      hydrolysis is obtained, the initial size of the nuclei depends on the silica
      concentration, with larger nuclei being present in more concentrated sols, while
      the rate of growth of primary particles depends on both silica concentration and
      solution pH. At low silica concentrations and high pHs, it was possible to
      observe the growth of stable, nonaggregating primary silica particles by a
      mechanism involving rapid nucleation followed by monomer addition. The presence
      of stable primary particles was confirmed by atomic force microscopy (AFM)
      imaging. At higher silica concentrations and lower pHs, there was an increase in
      the initial size of the nuclei formed, which subsequently grew to a larger radius
      (> 4.5 nm) or aggregated with time, and in such cases, nucleation and aggregation
      occurred simultaneously in the early stage of silica formation. The data clearly
      show the power of time-resolved fluorescence anisotropy decay measurements for
      probing the growth of silica colloids and show that this method is useful for
      elucidating the mechanism of particle formation and growth in situ.

PMID- 16459612
TI  - Soft- and hard-agglomerate aerosols made at high temperatures.
AB  - Criteria for aerosol synthesis of soft-agglomerate, hard-agglomerate, or even
      nonagglomerate particles are developed on the basis of particle sintering and
      coalescence. Agglomerate (or aggregate) particles are held together by weak,
      physical van der Waals forces (soft agglomerates) or by stronger chemical or
      sintering bonds (hard agglomerates). Accounting for simultaneous gas phase
      chemical reaction, coagulation, and sintering during the formation and growth of
      silica (SiO2) nanoparticles by silicon tetrachloride (SiCl4) oxidation and
      neglecting the spread of particle size distribution, the onset of hard
      agglomerate formation is identified at the end of full coalescence, while the
      onset of soft-agglomerate formation is identified at the end of sintering.
      Process conditions such as the precursor initial volume fraction, maximum
      temperature, residence time, and cooling rate are explored, identifying regions
      for the synthesis of particles with a controlled degree of agglomeration (ratio
      of collision to primary particle diameters).

PMID- 16459613
TI  - Two confined phases of argon adsorbed inside open single walled carbon nanotubes.
AB  - Isothermal adsorption of Ar on single walled carbon nanotubes (SWNTs) has been
      studied at 77 and 87 K. The SWNTs have been grown by laser vaporization of a
      graphite pellet containing 0.6% (atomic) Ni/Co catalyst. The nanotubes have been
      prepared for argon adsorption measurements by prolonged outgassing of as-grown
      material in a vacuum at room temperature (295 K), at elevated temperatures of up
      to 475 K, and by oxidization for 2 h in dry air at 470 K. Formation of two
      condensed phases of Ar in the interior of SWNTs has been observed at 77 K. The
      low-density phase is formed at 155(5) microTorr, while the high-density phase, at
      120(5) microTorr. At 87 K, only a single phase has been observed at 185(5)
      microTorr. Condensation at both 77 and 87 K appears to be the first-order phase
      transition. Onset of the quasi-one-dimensional linear (one-channel) phase and the
      quasi-two-dimensional monolayer (six-channel) phase formation on the external
      surface of bundles has been observed at 77 K near 0.0017 and 0.8 Torr,
      respectively, and at 87 K near 0.018 and 5 Torr, respectively. Isosteric heats of
      adsorption for the one-channel phase, the first external layer, and the second
      external layer have been determined to be equal to 137, 107, and 70 meV,
      respectively.

PMID- 16459614
TI  - Reactions of halobenzenes with methanol on the microporous solid acids hbeta,
      HZSM-5, and HSAPO-5: halogenation does not improve the hydrocarbon pool.
AB  - The reactions of fluorobenzene, 3-fluorotoluene, and three isomers of
      difluorotoluene, chlorobenzene, and bromobenzene with excesses of methanol were
      investigated on the large-pore catalysts HBeta (*BEA) and HSAPO-5 (AFI), and on
      the medium-pore HZSM-5 (MFI). Flow reactor studies in pulse mode with GC-MS
      detection revealed that the fluorobenzene derivatives were readily methylated at,
      for example, 375 degrees C, but not even pentamethylfluorobenzene was obviously
      active as a reaction center for methanol-to-olefin (MTO) catalysis. Carbon
      labeling studies revealed that small amounts of methylbenzenes were formed by
      defluorination, and these aromatic hydrocarbons seemed to account for the small
      yields of olefins (and their secondary reaction products) observed. Loss of one
      fluorine was also evident in the products for one of the difluorotoluene isomers.
      On HSAPO-5 the activity order for ring-methylation of halobenzenes was F > Cl >>
      Br. On HZSM-5, chlorobenzene and especially bromobenzene lost halogen through a
      route forming halomethane. These largely negative results will nevertheless be
      useful in testing theoretical models of the detailed reaction steps in the
      hydrocarbon pool mechanism for MTO catalysis.

PMID- 16459615
TI  - Fabrication of a gradient heterogeneous surface using homopolymers and diblock
      copolymers.
AB  - The strength of the interfacial interactions and the length scale over which
      these interactions occur are key factors in understanding the thin film behavior
      of polymer blends and diblock copolymers, adhesion, wettability, and recognition
      processes of cells and random heteropolymers on surfaces. Here, gradient
      heterogeneous surface topographies were prepared using thin films of mixtures of
      homopolymers and diblock copolymers to vary the lateral size scale of
      heterogeneities from the microscopic to nanoscopic. Dewetting, phase separation,
      and cell adhesion were used to demonstrate the utility of these surfaces having
      gradient heterogeneous topographies. By tuning the lateral size scale of the
      heterogeneities, surface patterns can be engineered to meet a specific function.
      Gradient surfaces offer a straightforward method to optimize various length
      scales of heterogeneity.

PMID- 16459616
TI  - Adsorption/desorption of mono- and diblock copolymers on surfaces using specific
      hydrogen bonding interactions.
AB  - Diblock copolymers containing recognition units designed to participate in
      specific three-point hydrogen bonding were adsorbed onto modified gold surfaces.
      Self-assembled monolayers (SAMs) containing complementary recognition units were
      used to direct the adsorption process. The polymer-modified surfaces obtained
      were characterized using X-ray photoelectron spectroscopy, water contact angle,
      and ellipsometry. The role of individual block lengths on the adsorption process
      was followed by observing frequency changes of thymine-SAM-modified quartz
      crystal microbalance chips during adsorption of diamidopyridine-functionalized
      polymers from a nonpolar solvent. The renewable nature of these recognition unit
      functionalized surfaces was demonstrated by reversible binding of polymers.
      Adsorption onto fresh surfaces, followed by desorption and subsequent
      readsorption of monoblock and diblock copolymers was also investigated.

PMID- 16459617
TI  - Formation processes of the integrated ordered mesostructure of silica at liquid
      liquid interface using synchrotron radiation X-rays.
AB  - The formation processes of the integrated ordered mesostructure of silica at the
      liquid-liquid interface in laurylamine/tetraethoxysilane system were elucidated
      by measuring the small-angle X-ray scattering pattern every second during the
      formation processes using strong synchrotron radiation X-rays. Cylinders of
      silica were formed in random configurations in the very early stage of reactions
      at the liquid-liquid interface. Since these cylinders were restricted in a two
      dimensional liquid-liquid interface, they aligned easily with each other and made
      an ordered structure composed of aligned cylinders at the interface. These
      ordered structures then accumulated with each other, making an integrated ordered
      structure, such as a hexagonal array.

PMID- 16459618
TI  - Lipid nanotubes and microtubes: experimental evidence for unsymmetrical monolayer
      membrane formation from unsymmetrical bolaamphiphiles.
AB  - Unsymmetrical bolaamphiphiles, omega- [N-beta-D-glucopyranosylcarbamoyl] alkanoic
      acids, with even-numbered oligomethylene chains (12, 14, 16, 18, and 20 carbons)
      self-assembled in water to form lipid nano- and microtubes. The tubular
      assemblies were separated by centrifugation and examined by transmission electron
      microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to
      study the molecular packing within the tubular membranes. The nanotubes
      encapsulated the staining reagent phosphotungstate, which revealed them to be
      hollow cylinders up to several hundred micrometers long with 30-43-nm outer
      diameters and 14-29-nm inner diameters. By comparing the membrane stacking
      periodicity obtained from powder X-ray diffraction analysis of the dehydrated
      tubes with the molecular packing within single crystals, we found that the
      nanotubes consist of an unsymmetrical monolayer lipid membrane (MLM) in which the
      molecules are packed in a parallel fashion. This suggests that the inner surface
      of the nanotubes is covered with carboxy headgroups and the outer surface with 1
      glucosamide headgroups. The inner diameters of the lipid nanotubes could be
      controlled in the range 17.7-22.2 nm in steps of approximately 1.5 nm/two carbons
      by varying the oligomethylene spacer length. The microtubes had three types of
      molecular arrangements. The first type was a symmetrical MLM in which the
      molecules were packed in an antiparallel fashion. The other two types had
      unsymmetrical MLM stacking with head-to-head and head-to-tail motifs. Increasing
      the number of oligomethylene spacers stabilized the unsymmetrical MLM structure
      in both nano- and microtubes.

PMID- 16459619
TI  - Bioinert solution-cross-linked hydrogen-bonded multilayers on colloidal
      particles.
AB  - Bioinert polyelectrolyte multilayers comprised of poly(acrylic acid) and
      polyacrylamide were deposited on colloidal particles (1.7 microm in diameter) at
      low pH conditions by layer-by-layer assembly using hydrogen-bonding interactions.
      The multilayer films were coated uniformly on the colloidal particles without
      causing any flocculation of the colloids, and the deposited films were
      subsequently cross-linked by a single treatment of a carbodiimide aqueous
      solution. The lightly cross-linked multilayer films show excellent stability at
      physiological conditions (pH 7.4, phosphate-buffered saline), whereas untreated
      multilayer films dissolved. The multilayer-coated surfaces, both on flat
      substrates and on colloidal particles, exhibit excellent resistance toward
      mammalian cell adhesion. With this new solution-based cross-linking method,
      bioinert H-bonded multilayer coatings offer potential for biomedical
      applications.

PMID- 16459620
TI  - Molecular-level control of feature separation in one-dimensional nanostructure
      assemblies formed by biomolecular nanolithography.
AB  - In this paper, we present a convenient and reliable method to organize small gold
      nanoparticles (d(CORE) = 1.5 nm) into linear chains with precisely controlled
      interparticle spacing over a range of 1.5-2.8 nm through biomolecular
      nanolithography. Controlling the feature separations of 1 to a few nanometers
      with angstrom-level precision is a key requirement in electronic and optical
      applications of nanostructures to tune the properties of the nanostructures and
      manipulate the interactions between neighboring structures. Here, chains are
      formed in solution by utilizing functional-group-directed self-assembly to
      organize ligand-stabilized gold nanoparticles onto DNA templates. The spacing
      between neighboring nanoparticles can be controlled chemically and tuned at the
      molecular level by utilizing nanoparticles possessing ligand shells of varying
      thickness to achieve angstrom-level resolution at spacings of 1.5, 2.1, and 2.8
      nm. The small standard deviation (< or = 20%) in the values for the interparticle
      spacing illustrates the reproducibility of the approach. Because the
      interparticle spacing is enforced by the ligand shell rather than the scaffold,
      the spacing is uniform even in nonlinear sections of the chain. We further show
      that the assembly process is robust and produces extended linear nanoparticle
      chains of up to 1 microm in length and a total coverage of > 90%. All structures
      and interparticle spacings were analyzed using transmission electron microscopy.
      Our results demonstrate the potential of scaffold-assisted assembly approaches
      for patterning features with tunable dimensions on a length scale that is
      important for future applications of these materials in nanoscale electronics and
      optics.

PMID- 16459621
TI  - In situ annealing and thickening of single crystals of C294H590 observed by
      atomic force microscopy.
AB  - The annealing behavior of twice-folded crystals of the long-chain alkane C294H590
      is examined in situ, in real time, by atomic force microscopy (AFM). AFM is
      capable of following processes in real time provided that the time scale is
      sufficiently long for several images to be collected during the process. In this
      paper, we focus on the temperature dependence and the thickened morphology. We
      are able to investigate where the thickening starts and how this depends on
      temperature and how melting is influenced by morphology. By following the motion
      of holes within the crystal, a lower limit for the rate of diffusion of
      crystalline polyethylene is estimated. We also focus on the substrate effect on
      the crystal morphology and thickening, using mica, glass, and graphite.

PMID- 16459622
TI  - Thin films of bicontinuous cubic mesostructured silica templated by a nonionic
      surfactant.
AB  - Thin films ofbicontinuous cubic mesostructured silica were formed using the
      nonionic poly(oxyethylene)-alkyl ether surfactant Brij-56 as a structure
      directing agent. The synthesis conditions were chosen such that the estimated
      volume fraction of surfactant in the silica/surfactant films corresponded
      approximately to the composition at which the bicontinuous cubic phase occurs in
      the water/surfactant phase diagram. Small-angle X-ray scattering and transmission
      electron microscopy measurements reveal that the cubic phase corresponds to the
      Ia3(-)d double-gyroid structure, with some distortion due to anisotropic film
      shrinkage. The cubic structure grows as faceted domains that are well-oriented
      with respect to the substrate and often occur in coexistence with a lamellar
      phase. By adjusting the temperature at which the films are aged, it is possible
      to create films with 2D hexagonal, cubic, or lamellar structures at a single
      composition.

PMID- 16459623
TI  - Multiarm molecular brushes: effect of the number of arms on the molecular weight
      polydispersity and surface ordering.
AB  - Individual molecules of multiarm starlike molecular brushes were visualized by
      atomic force microscopy. In the studied series of brushes, the number of arms
      varied from one for a linear chain to four, while the length of the side chains
      was kept approximately constant. Molecular visualization provided a unique
      opportunity for independent size characterization of the brush arms separately
      from that of the entire molecule. In agreement with the Schulz-Flory theory for
      chain coupling, the polydispersity of the total length was significantly lower
      than that of the arm length. The variation in polydispersity had an effect on
      molecular ordering. Lateral compression of the starlike brushes caused a
      transition from an extended dendritic-like conformation to a compact disklike
      conformation. In contrast to one-, two-, and three-arm brushes, the four-arm
      molecules with a lower polydispersity index of 1.04 demonstrated local hexagonal
      order.

PMID- 16459624
TI  - Synthesis and catalytic properties of soluble platinum nanoparticles protected by
      a thiol monolayer.
AB  - Several new platinum monolayer protected clusters (MPCs) have been synthesized
      and characterized. Two methods of platinum reduction were used depending on the
      solubility of the thiol: sodium borohydride for the water-soluble thiols and
      lithium triethylborohydride for the organic soluble thiols. In general, reactant
      solutions containing a 1:1 thiol/Pt ratio yielded the best particles in a single
      phase reaction. Higher thiol/Pt ratios produced lower yields of MPCs, while much
      lower ratios produced gray-black precipitates. The Pt MPCs were used as catalysts
      to hydrogenate allyl alcohol to propanol by reducing the carbon-carbon double
      bond. The Pt-mercaptoammonium MPCs were also used as catalysts in the
      hydrogenation of maleic acid to succinic acid. Differences in the catalytic
      hydrogenation rates among the various monolayer coatings for MPCs are attributed
      to the variations in ligand chain length, branching, charged functional groups,
      packing density, and core size.

PMID- 16459625
TI  - A direct route toward assembly of nanoparticle-carbon nanotube composite
      materials.
AB  - The preparation of nanocomposite materials from carbon nanotubes (CNTs) and metal
      or metal oxide nanoparticles has important implications to the development of
      advanced catalytic and sensory materials. This paper reports findings of an
      investigation of the preparation of nanoparticle-coated carbon nanotube composite
      materials. Our approach involves molecularly mediated assembly of monolayer
      capped nanoparticles on multiwalled CNTs via a combination of hydrophobic and
      hydrogen-bonding interactions between the capping/mediating shell and the CNT
      surface. The advantage of this route is that it does not require tedious surface
      modification of CNTs. We have demonstrated its simplicity and effectiveness for
      assembling alkanethiolate-capped gold nanoparticles of 2-5 nm core sizes onto
      CNTs with controllable coverage and spatially isolated character. The loading and
      distribution of the nanoparticles on CNTs depend on the relative concentrations
      of gold nanoparticles, CNTs, and mediating or linking agents. The composite
      nanomaterials can be dispersed in organic solvent, and the capping/linking shells
      can be removed by thermal treatment to produce controllable nanocrystals on the
      CNT surfaces. The nanocomposite materials are characterized using transmission
      electron microscopy and Fourier transform infrared spectroscopy techniques. The
      results will be discussed in terms of developing advanced catalytic and sensory
      nanomaterials.

PMID- 16459626
TI  - Phase separations in pH-responsive polyelectrolyte multilayers: charge extrusion
      versus charge expulsion.
AB  - Polyelectrolyte multilayers with continuously variable amounts of ionizable weak
      acid functionality were prepared by blending ionizable and nonionizable
      polyelectrolytes in the deposition solutions. Diluting ionizable groups in this
      way yielded multilayers that were more structurally stable, shown by thickness
      and atomic force microscopy measurements, as their internal polymer charge was
      varied by the pH of the external solution. Multilayers prepared with opposite
      surface charge to that appearing within the bulk (as a result of ionization) were
      more stable, as were thinner films, both results suggesting the extrusion of bulk
      charge to the surface. These multilayers were able to control the direction and
      magnitude of electroosmotic flow in microfluidics systems. Multilayers bearing
      only one, diluted layer ofionizable material were surprisingly effective in this
      respect.

PMID- 16459628
TI  - Phase diagrams of adsorption systems and calibration functions in the lattice-gas
      model.
AB  - Using the calibration function is suggested to increase the accuracy of
      approximate equations in the lattice-gas model at calculating various
      concentration dependences of equilibrium characteristics for nonideal adsorption
      systems in the vicinity of the critical point. This function should provide a
      shift of the approximate result to the exact one, when the lattice-gas model
      equations are used in the quality of the interpolation tool between the exact
      solutions. A comparison of approximate equations with Onsager's exact solution
      preferrably allows a use of the quasi-chemical approximation as the interpolation
      procedure and the exact information on the critical point. The modified lattice
      gas model takes into account next the molecular properties of the Lennard-Jones
      fluid: the long-range potential of adsorbate-adsorbate, an excluded volume of the
      adsorption site, and a contribution of the triple interactions, as well as a
      softness of the lattice structure. The modified lattice-gas model with the
      calibration function is used for the phase diagram descriptions for argon
      adsorption on the homogeneous (111) CdCl2 face (two-dimensional systems) and for
      methane adsorption in carbon slitlike pores (three-dimensional system) as well as
      the other equilibrium characteristics of mentioned systems.

PMID- 16459627
TI  - Functional and surface-active membranes from poly(vinylidene fluoride)-graft
      poly(acrylic acid) prepared via RAFT-mediated graft copolymerization.
AB  - Poly (vinylidene fluoride) (PVDF) with "living" poly (acrylic acid) (PAAc) side
      chains (PVDF-g-PAAc) was prepared by reversible addition-fragmentation chain
      transfer (RAFT)-mediated graft copolymerization of acrylic acid (AAc) with the
      ozone-pretreated PVDF. The chemical composition and structure of the copolymers
      were characterized by elemental analysis, Fourier transform infrared
      spectroscopy, and thermogravimetric analysis. The copolymer could be readily cast
      into pH-sensitive microfiltration (MF) membranes with enriched living PAAc graft
      chains on the surface (including the pore surfaces) by phase inversion in an
      aqueous medium. The surface composition of the membranes was determined by X-ray
      photoelectron spectroscopy. The morphology of the membranes was characterized by
      scanning electron microscopy. The pore size distribution of the membranes was
      found to be much more uniform than that of the corresponding membranes cast from
      PVDF-g-PAAc prepared by the "conventional" free-radical graft copolymerization
      process. Most important of all, the MF membranes with surface-tethered PAAc macro
      chain transfer agents, or the living membrane surfaces, could be further
      functionalized via surface-initiated block copolymerization with N
      isopropylacrylamide (NIPAAM) to obtain the PVDF-g-PAAc-b-PNIPAAM MF membranes,
      which exhibited both pH- and temperature-dependent permeability to aqueous media.

PMID- 16459629
TI  - Failure of elastomeric polymers due to rate dependent bond rupture.
AB  - A new cohesive zone model is developed in order to study the mechanisms of
      adhesive and cohesive failures of soft rubbery materials. The fracture energy is
      estimated here using a strategy similar to that of Lake and Thomas (LT) by
      considering the dissipation of stored elastic energy followed by the extension
      and relaxation of polymer chains. The current model, however, departs from that
      of LT in that the force needed to break an interfacial bond does not have a fixed
      value; instead, it depends on the thermal state of the system and the rate at
      which the force is transmitted to the bond. While the force required to rupture a
      chain is set by the rules of thermomechanically activated bond dissociation
      kinetics, extension of a polymer chain is modeled within both the linear and
      nonlinear models of chain elasticity. Closed form asymptotic solutions are
      obtained for the dependence of crack propagation speed on the energy release
      rate, which are valid in two regimes: (I) slow crack velocity or short relaxation
      time for bond dissociation; (II) fast crack velocity or long relaxation time for
      bond dissociation. The rate independent and the zero temperature limit of this
      theory correctly reduces to the fracture model of LT. Detailed comparisons are
      made with a previous work by Chaudhury et al. which carried out an approximate
      analysis of the same problem.

PMID- 16459630
TI  - Water ultrarepellency induced by nanocolumnar ZnO surface.

PMID- 16459632
TI  - Encapsulation of quantum nanodots in polystyrene and silica micro-/nanoparticles.

PMID- 16459631
TI  - Preconcentration of phenanthrene from aqueous solution by a slightly hydrophobic
      nonionic surfactant.

PMID- 16459633
TI  - Neoadjuvant oxaliplatin-based chemotherapy for liver metastases from colorectal
      cancer. An Italian survey.
AB  - BACKGROUND: Only 10% to 25% of patients with liver metastases from colorectal
      cancer are suitable for resection. Methods for increasing the resectability of
      liver metastases are based on specific surgical techniques and neoadjuvant
      chemotherapy. METHODS: We collected retrospective data on patients from various
      Italian hospitals from 1996 to 2002. Data from colorectal cancer patients with
      liver metastases treated with oxaliplatin-based neoadjuvant chemotherapy were
      considered. Analysis focused on patients and treatment description and on
      longterm survival. We considered 107 patients from 36 Italian hospitals. RESULTS:
      Of the 105 patients assessable for response, 8.4% achieved a complete response,
      70.1% a partial response and 19.6% stable disease. Ninety-nine patients were
      treated with surgery for liver metastases. A radical resection was achieved in
      79% of patients. Median survival time was 42 months. Thirteen patients
      experienced grade 3-4 hematologic toxicity, and 10 patients had grade 3-4
      nonhematologic toxicity. Neurologic toxicity of grade >1 was observed in 21% of
      patients. CONCLUSIONS: Neoadjuvant chemotherapy can be useful to increase the
      number of liver resections for metastatic colorectal cancer patients.
      Nevertheless, randomized trials are necessary to confirm this retrospective
      survey as well as the few single-institution experiences reported so far in the
      medical literature.

PMID- 16459635
TI  - Computed tomographic characterization of malignant peritoneal mesothelioma.
AB  - AIMS AND BACKGROUND: Peritoneal mesothelioma is a rare disease with a universally
      fatal outcome when managed in a traditional palliative manner. New approaches to
      treatment using cytoreductive surgery and intraperitoneal chemotherapy suggest
      that long-term survival is possible in selected patients. Early recognition of
      this disease process with an orderly surgical approach will begin to optimize
      treatment. METHODS: Thirty-three patients with malignant peritoneal mesothelioma
      had CT scans available for review. A Z-score was used to evaluate the incidence
      of cancer at a particular anatomic site as compared to a general incidence of
      disease at all sites. CT was analyzed by abdominopelvic anatomic sites (16),
      abdominopelvic regions (9), and for presence versus absence of disease in the
      chest. Interpretative CT findings (class 0-III) were determined for these 33
      patients. RESULTS: Eight of 33 patients had pleural abnormalities. In an analysis
      of 16 abdominopelvic anatomic sites, the vesical or rectal uterine pouch was
      involved in 97% and the greater omentum in 91%. These anatomic sites were the
      only ones with a positive Z-score of >1. In the analysis of 9 abdominopelvic
      regions, the central and pelvic regions had Z-scores >2 for large volume disease
      >5 cm. For CT interpretative findings class I, class II and class III was
      determined in approximately one-third in each category. Sixty-six percent of the
      patients had ascites by CT. CONCLUSIONS: Malignant peritoneal mesothelioma by CT
      evaluation predominates in tumor mass within the central and pelvic portions of
      the abdomen. Minimal, moderate, and extensive small bowel enlargements were seen
      in roughly one-third of the patients. With the use of the Z-score and
      interpretative small bowel findings a radiologic characterization of this disease
      for primary radiologic diagnosis is possible.

PMID- 16459634
TI  - A long-term follow-up analysis in adult acute myeloid leukemia patients after
      hematopoietic stem cell transplantation.
AB  - AIMS AND BACKGROUND: Over the last 17 years, 119 adult acute myeloid leukemia
      patients have undergone hematopoietic stem cell transplantation at our Center.
      STUDY DESIGN: Seventy patients in first complete remission received hematopoietic
      stem cell transplantation (28 allogeneic and 42 autologous HSCT) as late
      intensification after conventional chemotherapy; 38 patients received allogeneic
      hematopoietic stem cell transplantation in a more advanced phase. A reference
      group was built up by collecting 40 acute myeloid leukemia patients who received
      high-dose cytosine arabinoside as late intensification and whose complete
      remission lasted more than 10 months. RESULTS: Results of the study led to
      conclude that an earlier timing of allogeneic hematopoietic stem cell
      transplantation can be recommended in order to treat patients who would otherwise
      suffer an early relapse. CONCLUSIONS: The outcome of autologous hematopoietic
      stem cell transplantation in patients not in first complete remission supports
      the possibility of achieving good quality second complete remissions and suggests
      that autografting may be a life-saving strategy in selected acute myeloid
      leukemia patients with advanced disease.

PMID- 16459636
TI  - The predictive value of clinical evaluation of response to neoadjuvant
      chemoradiation therapy for rectal cancer.
AB  - INTRODUCTION: Multimodality therapy has become the standard treatment for
      patients with locally advanced (T3 and T4) rectal carcinoma. Accurate
      preoperative staging of the patients with rectal cancer has increased in
      importance because the selection of patients with transmural rectal cancer (T3 or
      T4) or node-positive disease leads to a previous nonsurgical neoadjuvant
      treatment. The purpose of this study was to evaluate the predictive value of the
      clinical response to neoadjuvant therapy on the basis of pathological results
      obtained on rectal cancer patients treated by chemoradiotherapy and surgery.
      METHODS: From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer
      were studied at our department and enrolled in a neoadjuvant protocol of
      chemoradiotherapy followed by surgery. All patients were treated by 30 days of
      chemoradiotherapy. At the end of the chemoradiotherapy, each patient underwent
      clinical examination, including digital rectal examination, proctoscopy and
      abdominal-pelvic computerized tomography to define the clinical response to the
      chemoradiotherapy. Surgical resection was performed in all patients three weeks
      after the end of chemoradiotherapy, and histological analysis was performed on
      all resected specimens. RESULTS: The clinical complete response rate corresponded
      to the pathological complete response rate, whereas the clinical evaluation
      overestimated partial response and stable disease. The pathologic examination
      revealed that 3.5% of clinical partial responses and 3.4% of clinical stable
      disease were really pathological progressive disease. Clinical partial response
      and clinical stable disease positive predictive values were 92.8% and 90.9%,
      respectively, whereas the clinical progressive disease negative predictive value
      was 20%. Then, 6.9% of patients believed to have responded to the therapy, or not
      to have responded or worsened, actually had worsened by the end of the
      chemoradiotherapy. CONCLUSIONS: Positive and negative predictive values, in
      particular for partial response and stable disease, of clinical evaluation of the
      response to chemoradiotherapy were not high enough to consider clinical
      evaluation accurate enough to make treatment decisions.

PMID- 16459638
TI  - Sampling of internal mammary chain lymph nodes during breast reconstruction by
      free flaps from the abdomen.
AB  - The role of internal mammary chain lymph node removal in breast cancer is still
      not clarified. Although it has been proven that elective dissection of the
      internal mammary chain nodes does not improve survival, their selective treatment
      based on sentinel lymph node biopsy is under evaluation. There is another
      possibility to establish the status of internal mammary chain nodes--sampling of
      the nodes during the preparation of the site for microvascular anastomosis to the
      internal mammary artery and vein for free flap transfer. From August 2002 to
      December 2003, 54 free flaps were performed for breast reconstruction. In 11
      cases, an internal mammary chain lymph node was harvested. A positive internal
      mammary chain node was found in only one case. In this case, the treatment policy
      was changed by adding irradiation to the internal mammary chain. The sampling of
      internal mammary chain nodes during preparation of the site for microvascular
      anastomosis to the internal mammary artery and vein should be a part of the
      reconstructive procedure after total mastectomy for invasive breast cancer
      because it could change the treatment plan.

PMID- 16459637
TI  - Concomitant chemotherapy and external radiotherapy plus brachytherapy for locally
      advanced esophageal cancer: results of a retrospective multicenter study.
AB  - AIMS AND BACKGROUND: In October 1995, the Piedmont AIRO (Italian Society of
      Radiation Oncology) Group started a multi-institutional study of
      radiochemotherapy on locally advanced esophageal cancer, characterized by
      external radiotherapy followed by an intraluminal high dose-rate brachytherapy
      boost. Most patients were re-evaluated for surgery at the end of the program. The
      primary aim of the study was to assess efficacy of curative radiochemotherapy
      regarding overall survival and local control rates. The secondary aim was to
      evaluate the ability of radiochemotherapy to make resectable lesions previously
      considered inoperable. METHODS AND STUDY DESIGN: Between January 1996 and March
      2000, 75 patients with locally advanced esophageal cancer were enrolled. All were
      treated with definitive radiotherapy; due to age or high expected toxicity,
      chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60
      Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with
      two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5).
      One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were
      carried out on patients whose restaging showed a major tumor response. Surgery
      was performed in 14 patients. RESULTS: At the end of radiotherapy, dysphagia
      disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom
      reduction was recorded. Complete objective response at restaging after
      radiotherapy was obtained in 33% of patients and a partial response in 53%. At
      the end of the multimodal treatment program, including esophagectomy, complete
      responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pT0) at
      pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall
      survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year
      local control rates were, respectively, 35% and 33%. In a subgroup of 20
      nonsurgical patients in complete response after radiochemotherapy, the overall
      survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5
      years was 75%. According to multivariate analysis, prognostic factors for
      survival were Karnofsky index and esophagectomy. CONCLUSIONS: For patients with
      locally advanced disease, radiochemotherapy showed improved clinical and
      pathologic tumor response and survival compared to surgery or radiotherapy alone.
      Intraluminal brachytherapy with a small fraction size allows an increased dose to
      the tumor without higher toxicity. Esophagectomy following radiochemotherapy
      could improve survival rates compared to definitive radiochemotherapy, but it is
      necessary to optimize selection criteria for surgery at the re-evaluation phase.

PMID- 16459639
TI  - Squamous cell carcinoma of the breast diagnosis by vacuum-assisted core biopsy.
AB  - Squamous cell breast carcinoma is a rare occurrence. Often the tumor is
      metastatic from an extramammary primary tumor. In order to determine the nature
      of the lesion, extensive sampling is necessary. We report a case of primary
      squamous cell carcinoma of the breast diagnosed by vacuum-assisted core biopsy.

PMID- 16459641
TI  - Single colon metastasis from breast cancer: a clinical case report.
AB  - Metastatic involvement of the extrahepatic digestive system is rare. We here
      report the case of a 62-year-old woman who presented with a bowel obstruction
      related to a metastasis of breast cancer occurring 12 years after a mastectomy
      for lobular carcinoma. No other distant metastases were detected except for two
      nodules of 20 and 5 mm on the right chest wall. Biopsy of the larger nodule
      showed a lobular carcinoma. The patient underwent a right hemicolectomy and then
      received chemotherapy combined with letrozole, resulting in a partial response.
      The literature revealed only a few cases of breast cancer metastatic to the
      colon. Patients with known breast cancer, particularly of the lobular
      histological type, who present with specific or less specific abdominal symptoms
      or signs such a microcytic anemia, should be endoscopically explored in order to
      detect possible metastases of the primary breast tumor.

PMID- 16459640
TI  - Unusual complication after radiotherapy for breast cancer bronchiolitis
      obliterans organizing pneumonia case report and review of the literature.
AB  - Breast-conserving surgery and postoperative radiotherapy play an important role
      in the treatment of early breast cancer. Bronchiolitis obliterans with organizing
      pneumonia (BOOP) is an uncommon syndrome reported to be one of the complications
      of adjuvant radiotherapy. We report the case of a 71-year-old woman who developed
      cough, dyspnea and fever three weeks after radiation therapy to the left breast
      for breast carcinoma. Chest X-ray and computed tomography scan demonstrated
      alveolar opacities within both lungs. Antibiotic therapy against any probable
      septic pathology did not improve the symptoms, while corticosteroid treatment
      resulted in rapid clinical improvement together with regression of the pulmonary
      opacities. Irradiation was thought to be the cause of the migratory pneumonitis,
      hence this case was clinically diagnosed as radiation-induced migratory
      pneumonitis similar to BOOP, without lung biopsy. The present case suggests that
      one should be mindful of this disease when treating patients with a history of
      irradiation to the breast. BOOP promptly responds to systemic corticosteroid
      therapy with rapid improvement of symptoms and regression of the pulmonary
      opacities.

PMID- 16459642
TI  - Retrobulbar metastasis from gallbladder carcinoma after laparoscopic
      cholecystectomy. A case report.
AB  - Extra-abdominal metastases from gallbladder cancer are very rare; the sites
      outside the abdomen most frequently affected are the skin, bone and central
      nervous system. In the literature, only one case of orbital metastasis from
      gallbladder cancer has been reported, in a patient previously treated by open
      cholecystectomy. We report the case of a 53-year-old woman who underwent a
      laparoscopic cholecystectomy for symptomatic gallbladder stones. Postoperative
      histological examination revealed an unsuspected gallbladder adenocarcinoma. One
      month later she came to our observation after having developed diplopia and
      ophthalmic pain due to an orbital metastasis. We decided not to perform a
      surgical second look because of the already rapid dissemination of the malignant
      tumor. The few cases of uncommon gallbladder cancer metastases after laparoscopic
      cholecystectomy described in the literature are discussed, as well as the
      possible role of laparoscopy in the dissemination and localized seeding of
      malignant cells.

PMID- 16459643
TI  - Cavernous hemangioma of the gallbladder. Case report and review of the
      literature.
AB  - Hemangiomas are common benign tumors; they frequently occur in the liver but very
      rarely in the gallbladder, with only seven cases reported in the scientific
      literature to date. We here report an additional patient, a 49-year-old white
      woman presenting with an echogenic lesion of the gallbladder that was
      incidentally discovered. Cholecystectomy was performed after computed tomography
      had revealed a gallbladder neoplasm; pathological examination showed the mass to
      be a cavernous hemangioma. No postoperative complications occurred and the
      patient is alive and free of recurrence five years after the operation. We
      present a review of the literature on this topic with special emphasis on the
      diagnostic and therapeutic challenges these lesions may entail. Hemangiomas of
      the gallbladder may have extremely variable presentations (from non-specific
      abdominal pain to acute syndromes resembling cholangitis or choledocholithiasis)
      and can mimic different lesions (liver tumors, sarcoma). Only surgical
      exploration can provide a correct diagnosis. Excision is indicated as these
      lesions may grow to huge sizes, compress adjacent structures or bleed.
      CONCLUSIONS: Gallbladder hemangiomas are uncommon benign tumors. A preoperative
      diagnosis is difficult to make. Surgical excision is mandatory both in reaching a
      final diagnosis and in preventing bleeding or compression of vital structures.

PMID- 16459644
TI  - Epithelioid sarcoma-like hemangioendothelioma: a case report.
AB  - Seven cases of an unusual low-grade vascular tumor were reported in a recent
      study. Despite its similarity to epithelioid sarcoma, this tumor was termed
      epithelioid sarcoma-like hemangioendothelioma because of the subtle
      histopathological and immunohistochemical differences. Another case of this rare
      entity in a 70-year-old woman who suffered from a painful mass on the anterior
      aspect of the right cubital fossa is presented here, together with a review of
      the relevant literature.

PMID- 16459645
TI  - Primary squamous cell carcinoma of the stomach: a case report.
AB  - Squamous cell carcinoma (SCC) originating from the stomach is a relatively rare
      entity. There are theories regarding the development of this rare tumor, but its
      exact pathogenesis remains obscure. Fewer than 100 cases of primary SCC of the
      stomach have been presented in the literature. Due to the advanced stage at the
      time of diagnosis in most of these cases, the prognosis is generally poor. In the
      case presented here, dissemination of the tumor to the transverse colon,
      gallbladder and omentum was present at diagnosis. Despite the tumor's advanced
      stage, complete remission was achieved after six courses of adjuvant chemotherapy
      with 5-flourouracil and cisplatin. No recurrence has been detected during follow
      up. The patient has been healthy with no sign of the disease for three years.

PMID- 16459646
TI  - Retrospective, single-institution study on patterns of failure in male breast
      carcinoma patients after external beam radiotherapy.

PMID- 16459647
TI  - [The Oxford meta-analysis of 2000: reflections and comments].

PMID- 16459648
TI  - [Meningeal carcinomatosis in cancer patients].

PMID- 16459650
TI  - The effect of RAB5A gene on rearrangement of microfilaments in human lung
      adenocarcinoma cells.
AB  - To study the effect of RAB5A gene on microfilaments in human lung adenocarcinoma
      cells, AGZY83-a cells were stained with fluorescein isothiocyanate (FITC)
      phalloidin. Microfilament bundles in RAB5A gene over-expressed AGZY83-a cells
      were shown to be denser than in control cells using confocal laser scanning
      microscope (CLSM). According to the analysis of Tumor Metastasis Microarray on
      RAB5A gene, three genes related to the regulation of cytoskeleton were
      identified, including NM23H1, Rac1 (downregulated in RAB5A over expressing
      cells), and S100A4 (upregulated in RAB5A overexpressing cells). Previous studies
      demonstrated that S100A4 gene functioned to suppress the expression of NM23H1
      gene. To test if this elevated expression of S100A4 results in the down
      regulation of NM23H1, RNAi was applied to silence the expression of S100A4 in
      AGZY83-a cells. Our data indicated that expression of NM23H1 was increased
      following the inhibition of S100A4 expression. Altogether, the results indicated
      that RAB5A gene was involved in the suppression of expression of NM23H1 by
      promoting the expression of S100A4.

PMID- 16459649
TI  - [Zoledronic acid and bone pathology in the course of neoplasia. Part I].

PMID- 16459651
TI  - [Association study between NPY and YWHAH gene polymorphisms and schizophrenia].
AB  - A case-control study was carried out on a sample of 583 cases vs. 372 controls in
      the Chinese Han population, investigating several published polymorphisms in the
      YWHAH and NPY genes, which reported to be associated with schizophrenia. The
      polymorphism -134 (GCCTGCA)2-4, in the YWHAH was not analyzed for the failure of
      amplification, and the polymorphism T1128C in the NPY is not existent in the
      samples. The analysis was then emphasized on the variants -485C > T(NPY) and
      G753A(YWHAH). However, no significant differences of allele frequencies (with P
      values of 0.696 and 0.743, OR values of 1.041 and 0.962 respectively) or genotype
      frequencies (with P value of 0.45 and 0.75, chi2 = 1.51 and 0.58 respectively)
      among the matched groups were found. No sex-dependent effect was found either.
      Also,the analysis of the relative risk between the genotypes of the two genes
      indicates that the two genes could not cooperate with each other to add the risk
      of disease (P > 0.05). The results suggest that the polymorphisms - 485C > T
      (NPY) and G753A (YWHAH) are unlikely to be linked with genetic susceptibility to
      schizophrenia in the Chinese Han population.

PMID- 16459652
TI  - Generation of transgenic mice with liver-specific expression of human nuclear
      receptor nr5a2.
AB  - Human nuclear receptor hb1 f(nr5a2) was cloned and characterized as a novel
      member of the Ftz-F1 (nr5a) nuclear receptor subfamily,whose its biological
      function remained largely unidentified. The aim of this study was to establish
      transgenic mouse model that specifically expressed hB1F in the liver to faciliate
      the functional study of hB1F. hb1f cDNA was placed downstream of mouse albumin
      gene enhancer/promoter to construct a liver-specific hb1f expression vector.
      Transgene fragments were microinjected into fertilized eggs of mice. The
      manipulated embryos were transferred into the oviducts of pseudopregnant female
      mice. Four offspring were identified as carrying the transgenes by PCR,from which
      one was also verified by Southern blotting. RT-PCR and Western blotting results
      showed that the transgene was expressed in the liver of the transgenic mice.
      Transgenic founder mice were used to establish transgenic mouse lineages. The F1
      mice were identified by PCR analysis. Genetic analysis of the transgenic mice
      demonstrated that the transgene had been integrated into the chromosome at a
      single site and could be stably transmitted.

PMID- 16459653
TI  - Construction and characterization of a recombinant pseudorabies virus expressing
      porcine reproductive and respiratory syndrome virus GP5.
AB  - The GP5 gene of porcine reproductive and respiratory syndrome virus (PRRSV) was
      integrated into the TK gene locus of pseudorabies virus (PRV) vaccine strain
      Bartha-K61, resulting in a TK- and gE- negative recombinant PRV harboring GP5
      gene, designated as rPRV-GP5. The in vitro expression of the GP5 by rPRV-GP5
      infected cells was analyzed by single-step growth analysis,Western blot,and
      indirect immunofluorescence test. It was shown that GP5 gene can be expressed
      authentically in the cytoplasm of rPRV-GP5-infected cells. Compared to its
      parental virus, rPRV-GP5 showed no obvious difference regarding viral replication
      and cytopathogenic effects in several cell cultures. Four PRV-negative sheep
      immunized intramuscularly with 10(6.0) PFU of rPRV-GP5 were fully protected from
      challenge with 10(3) LD50 of highly virulent PRV S strain of porcine origin. Ten
      PRV- and PRRSV-negative piglets given intranasally with 10(7.0) PFU of rPRV-GP5
      and challenged intranasally with 10(5.0) TCID50 of virulent PRRSV CH-1a strain at
      day 63 post-inoculation developed antibodies against PRRSV 3, 5, 14 days post
      challenge, as revealed by indirect immunofluorescence test, enzyme-linked
      immunosorbent assay and virus neutralization test. The results suggest that rPRV
      GP5 is capable of inducing anamnestic immune response to PRRS in inoculated
      animals.

PMID- 16459654
TI  - [Origin and genetic diversity of Mongolian and Chinese sheep using mitochondrial
      DNA D-loop sequences].
AB  - To determine the origin and gene diversity of the Chinese and Mongolian domestic
      sheep, a partial fragment of mitochondrial DNA D-loop was sequenced for total
      number of 314 individuals from nine Chinese sheep populations and 11 Mongolian
      sheep populations. The results show no difference in nucleotide composition
      between Chinese and Mongolian sheep mtDNA D-loop sequences. However, more
      variables were identified in Mongolian sheep (26.85% of the sites) than that in
      Chinese sheep (24.22%). In China, mtDNA haplotype diversity was the highest in
      Qinghai Tibetan sheep, followed then by Gansu Tibetan sheep, Gansu Alpine Merino,
      Qinghai Merino, Gannan Tibetan sheep, Small-tailed Han sheep, Tan sheep, Hu sheep
      and Minxian Black Fur sheep. In Mongolian sheep, mtDNA haplotype diversity was
      the highest in Bayad and Baidrag populations and the lowest in the Gobi-Altai
      population. In general, Mongolian sheep have a richer genetic diversity than the
      Chinese ones with larger number of haplotypes (86.06% (142/165) versus 78.83%
      (108/137)), higher haplotype diversity (Hd; 0.976 versus 0.936), higher
      nucleotide diversity (Pi (pi); 0. 036 versus 0.034) and higher average number of
      nucleotide differences (k; 23.50 versus 22.48). Phylogenetic analysis of the 217
      haplotypes identified in both Mongolian and Chinese sheep supported the same
      origin of their domestication with three distinct maternal lineages defined as
      major haplotypes A, B and C, of which haplotype A are the commonest in all
      Chinese sheep populations and in the majority of Mongolian sheep populations
      (9/11) with an average frequency of 58.73%, followed by haplotype B present in
      eight of Chinese population and in all Mongolian sheep populations with an
      average frequency of 24.68%, and haplotype C present in eight Chinese and in 10
      Mongolian sheep populations with an average frequency of 16.59%. Further network
      analysis of the phylogenetic relationship of the 87 haplotypes identified from 91
      sequences retrieved from GenBank together with the 217 haplotypes detected in
      this study reveals clearly four distinct lineages with the European mouflon (O.
      musimon) mixed into one of the lineages (haplotype B). There is no evidence of
      contribution of Argali sheep (O. ammon), O. vignei bochariensis and/or O. ammon
      nigrimontana to the maternal origin of both Mongolian and Chinese domestic sheep.

PMID- 16459655
TI  - Function analysis of promoter trapping system after inserted into cotton
      (Gossypium hirsutum L. ) genome.
AB  - The technique of promoter trapping was developed to investigate its viability in
      cotton ( Gossypium hirsutum L.) functional genomics. 141 independent
      transformants of cotton were generated via Agrobacterium tumefaciens mediated
      transformation, of which 97% showed positive by PCR detection. The reporter, GUS
      gene, was expressed to different extent in different organs, with a frequency of
      48% in roots, 9.2% in vascular bundles of stem, 5.2% in leaves, and 51% in
      flowers. Meanwhile, we discovered that there existed great differences in
      expression patterns among different transgenic lines. Their GUS expression
      patterns were organ- or tissue-specific or ubiquitous in all of the plants. The
      promoter trapping system developed here was characterized as an effective method
      for creating mutants with diverse reporter gene expression patterns, which laid a
      solid foundation for further research of functional genomics in cotton.

PMID- 16459656
TI  - Molecular marker assisted selection and pyramiding of two QTLs for fiber strength
      in upland cotton.
AB  - Based on two major QTLs that control high fiber strength which originated from an
      elite fiber germ-plasm line 7235 (Gossypium hiusutum L.), the efficiency of
      molecular marker-assisted selection (MAS) was investigated using two populations
      from pedigree selection and modified backcrossing pyramiding developed for the
      breeding purpose. Simian 3 (SM3), a widely planted variety in the Yangtze River
      Valley, and 7235 were used as parents to develop the two populations. In the two
      major QTLs for fiber strength from 7235, QTLfs-1 could explain more than 30% of
      the phenotypic variation (PV) in the (7235 x TM-1) F2 population. QTLfs-2 was at
      first identified in another super quality fiber line HS427-10 from (HS427-10 x TM
      1) F2 population with 12.5% of PV explanation,which was further also identified
      in 7235 line but was non-allelic with QTLfs-1. The result of molecular marker
      assisted selection for fiber strength showed that the genetic effect of the QTLfs
      1 was stable under different environmental conditions, and its molecular marker
      assisted selection showed significant selective efficiency among breeding
      populations with different genetic backgrounds. QTLfs-2 also showed high
      selective efficiency in advanced generation populations though its effect was a
      little lower than the former. When QTLfs-1 was selected simultaneously with 2
      molecular markers with known genetic distance, the selection efficiency for the
      fiber strength was greatly increased. The pyramiding for two QTLs that control
      high fiber strength by MAS greatly improved the selection efficiency for cotton
      fiber strength. This report provides a successful example of MAS pyramiding for
      QTL for favorable traits in breeding programs.

PMID- 16459657
TI  - [Effects of divergent habitat on genetic structure of population of Excoecaria
      agallocha, a mangrove associate].
AB  - Genetic diversity and population genetic structure of Excoecaria agallocha, a
      typical mangrove associate species,were surveyed at divergent habitats
      (intertidal and inland). In general, intertidal populations had higher genetic
      diversity than inland populations. Genetic differentiation among intertidal
      populations (G(ST) = 0.191) were smaller than that among inland populations
      (G(ST) = 0.218), suggesting that gene flow via seed among intertidal populations
      were stronger. In an analysis of molecular variance (AMOVA), we found that 15.13%
      of the genetic variance could be explained by the differentiation between
      habitats, as compared to only 11.63% to geographical effects among five sits 181 
      759 km distant from each other. This implies that markedly selection regimes
      result in habitat adaptation. Isolation-by-distance, Southwest Monsoon
      Current,China Coastal Current and genetic drift played important role in genetic
      differentiation of China population of Excoecaria agalocha.

PMID- 16459658
TI  - [Development of transgenic oilseed plants resistant to glyphosate and insects].
AB  - In this study, the aroA-M12 gene encoding bacterial 5-enolpyruvylshikimate-3
      phosphate synthase (EPSPS) and the Btslm recombinant gene encoding Bacillus
      thuringiensis (Bt) toxin gene were introduced into a Brassica napus variety,
      Xiangyou No. 15, via Agrobacterium-mediated transformation using glyphosate as a
      selectable agent. PCR amplification and Southern blot analyses of T0 transgenic
      plants showed that the alien genes were transferred and integrated stably into
      the genome of Xiangyou No. 15. Western blot further confirmed that the alien
      genes were expressed in these plants. Transgenic plants with tolerance to both
      glyphosate and the tested pest were demonstrated by bioassays. Our result also
      clearly shows that the aroA-M12 gene can be used as an efficient selectable
      marker gene instead of antibiotic resistant markers in plant transformation.

PMID- 16459659
TI  - [Influence of B mating-type factor on recovery of nuclear types from dikaryons in
      Lentinula edodes].
AB  - This study determined a genetic basis for the phenomenon of significant
      asymmetric ratio of the two component nuclear types from dikaryons of Lentinula
      edodes via protoplast formation and regeneration by clarifying the influence of A
      or B mating-type factor on recovery of nuclear types from dikuaryons. The results
      revealed that B factor or some supposed genes linked to the B factor appeared to
      influence survival of dedikaryotized nuclei,whereas A factor had no apparent
      effect on this phenomenon. Specificity of B factor was shown to correlate with
      percentage survival of the component nuclear types recovered from both kinds of
      heterokaryons (A not equal to B not equal to and A = B not equal to). It can be
      put in an hierarchical order with respect to this function,the hierarchical order
      of these B factors was B1 > B3 > B4 > B2 between two tested strains.

PMID- 16459660
TI  - [Expression and immunization testing of fusion protein of Newcastle disease virus
      in leaf tissue of transgenic rice].
AB  - Transgenic plant is an attractive bioreactor to produce recombinant protein, such
      as safe and economic vaccine. In present study, a plant expression binary vector
      pUNDV, containing the 1.7 kb fusion protein gene of Newcastle Disease Virus (NDV
      F) under the control of maize ubiquitin (Ubi) promoter and nos terminator was
      constructed, in which, the Hygromycin phosphotransferase (HPT) gene was used as
      the selectable marker. The expression cassette was introduced into a japonica
      rice variety by Agrobacterium-mediated transformation, and 6 independent
      transgenic rice lines were regenerated and verified by hygromycin resistance
      selection. The integration of target gene in transgenic plants was confirmed by
      PCR analysis. The results from ELISA and Western blot analyses revealed that NDV
      F could be expressed in the leaf of several transgenic plants. The total salt
      soluble proteins were extracted from leaf of transgenic plant F5, which contained
      the highest expressing level of NDV F protein, and used in immunization of BALB/c
      mice. The specific antibodies could be elicited in mice immunized with NDV F
      protein expressed in transgenic rice.

PMID- 16459661
TI  - Nuclear matrices and matrix attachment regions from Green alga: Dunaliella
      salina.
AB  - Nuclear DNA of eukaryotic organism attaches to the proteinaceous nuclear matrices
      via specific matrix attachment regions (MARs). In order to investigate the
      interactions between chromosomal DNA and nuclear matrices,we isolated the MARs
      from unicellular alga Dunaliella salina. As the first step,a random MAR library
      was set up and then the binding affinity of the selected clones to nuclear
      matrices was tested in this study. Three DNA fragments were found to bind
      specifically to the nuclear matrices in vitro,of which two were strong binders
      and all contained known consensus motifs and a hairpin loop structure of MAR.

PMID- 16459662
TI  - [Molecular basic of interaction between disease resistance gene and avirulence
      gene].
AB  - Plant-pathogen interaction is the more important phytopathological subjects.
      Landmark progress in the past 10 years have resulted in the identification of
      functional R genes from the host and Avr genes from the pathogen,additionally
      interaction between their encoded productions. This paper reviewed the two models
      of R-Avr interaction, namely "receptor-ligand model" and "guard model", and
      discussed how to utilize the R gene during crop breeding and commercial
      production.

PMID- 16459663
TI  - [Progress in the study on diacylgycerol acyltransferase (DGAT)-related genes].
AB  - Diacylgycerol Acyltransferase (DGAT) plays an important role in the formation of
      lipid in different tissues of biological body. DGAT catalyzes the final step in
      triacylglycerol (TAG) biosynthesis by converting diacylgycerol (DAG) and fatty
      acyl-coenzyme A (CoA) into triacylglycerol. This enzyme is coded by both DGAT1
      and DGAT2. DGAT1 belongs to the gene family of cholesterol acyltransferase
      (ACAT). DGAT2 belongs to the gene family of monoacylgycerol acyltransferases
      (MGAT1). This paper reviewed the structure, location on chromosome and biological
      effect of DGAT-related genes. The relationship between polymorphism and
      performance of animal was also discussed.

PMID- 16459664
TI  - [Follow-up of renal cancer. Guidelines of the Comite de Cancerologie de
      l'Association Francaise d'Urologie].
AB  - The follow-up of renal cancer is essentially based on thoracoabdominal computed
      tomography (CT). The duration of this follow-up and the frequency of examinations
      depend on the patient's level of risk. Early detection of metastases has a
      limited therapeutic value at the present time, apart from tumours with a good
      prognosis or for the management of complications. Recent publications on targeted
      treatments raise new hopes and may lead to a modification of follow-up
      guidelines.

PMID- 16459665
TI  - [Follow-up of urothelial tumours. Guidelines of the Comite de Cancerologie de
      l'Association Francaise d'Urologie].
AB  - The follow-up of urothelial tumours is designed to allow early detection of
      recurrence or progression, for which treatment is possible. Recent interesting
      points are: the more frequent and simpler use of the new classification into low
      grade and high grade, essentially applied to the management and surveillance of
      tumours involving the mucosa or lamina propria; and the limited place of urinary
      markers.

PMID- 16459666
TI  - [Follow-up of prostate cancer. Guidelines of the Comite de Cancerologie de
      l'Association Francaise d'Urologie].
AB  - The follow-up of prostate cancer is especially justified now that effective
      treatment options are available in the case of recurrence. Conditions of follow
      up of patients with prostate cancer vary according to age, comorbidities, tumour
      stage, prognostic factors at diagnosis and the pervious treatment sequence.

PMID- 16459667
TI  - [Follow-up of testicular germ cell tumours. Guidelines of the Comite de
      Cancerologie de l'Association Francaise d'Urologie].
AB  - The follow-up of testicular tumours must be rigorous in view of the high cure
      rate in the case of recurrence. This follow-up is based on clinical examination,
      thoracoabdominopelvic CT and the tumour marker assays. The frequency of these
      examinations depends on the tumour stage.

PMID- 16459668
TI  - [Follow-up of malignant tumours of the penis. Guidelines of the Comite de
      Cancerologie de l'Association Francaise d'Urologie].
AB  - Tumours of the penis are potentially serious tumours, but are uncommon in western
      countries. Follow-up is based on clinical examination and thoracoabdominopelvic
      CT scan.

PMID- 16459669
TI  - [Diagnosis of urogenital infection by Chlamydia trachomatis. Contribution of
      genetic amplification techniques].
AB  - The majority of patients with Chlamydia trachomatis infection are not aware of
      ther infection because they do not have symptoms. Therefore, infected individuals
      may not be identifiable, and chlamydial infection in men may persis for long
      periods, and can lead to complications such as epididymitis and prostatis. The
      large group of asymptomatically infected patients is not only at risk of long
      term sequelate but also sustains transmission within communities. In asymptomatic
      and in chronic or persistent chlamydial infections, the level of Chlamydia is
      very low, and consequently chlamydial infections have never been easy to
      diagnose. The diagnosis may be based on cell culture, direct detection bacterial
      antigens, the nucleic acid amplification tests (NAATs) which have become the
      method of choice, and on the evaluation of antibody titers against various
      antigenic constituents. Both systemic and local antibodies in secretions can be
      detected in C. trachomatis infection. The introduction of assays based on
      amplification of genetic material has subsequently increased the sensitivity of
      detecting chlamydial infections and offer the opportunity to use non invasive
      specimens such as first void urine and semen to screen infections either in
      asymptomatic subjects or male partners of infertile couples. Cell culture or
      direct detection of bacterial antigens cannot be used for semen and urine samples
      and are not sensitive enough to rule out infections. Advantages of NAATs are the
      ability to detect even a small amount of organisms. This enables a high detection
      rate for C. trachomatis in symptomatic patients, in asymptomatic individuals with
      a low number of elementary bodies, and diagnosis of persistent infections.

PMID- 16459670
TI  - [Uro-genital tuberculosis].

PMID- 16459671
TI  - [Anaemia and prostatic cancer].
AB  - Abnormal laboratory parameters are frequently observed during the course of
      prostate cancer. Anaemia, often due to multifactorial causes, develops
      progressively and essentially depends on the stage of the disease and the
      therapeutic strategy. Androgen deprivation can induce a reduction of haemoglobin
      that can sometimes be severe, especially in the case of complete hormonal
      blockade. At a time when the extension of the indications for hormonal blockade
      in combination with external beam radiotherapy in localized prostate cancers
      appears to be confirmed, the long-term adverse effects need to be monitored more
      closely. External beam radiotherapy is also responsible for a fall in
      haemoglobin, which depends on the dimensions of the irradiation field and the
      volume of bone marrow included in the field. However progress in irradiation
      techniques should result in decreased haematological toxicity. Anaemia inevitably
      affects the patient's quality of life and also appears to have a negative impact
      on local control of localized prostate cancer treated by external beam
      radiotherapy. The indications for early and preventive management of anaemia must
      be defined. Furthermore, as treatment of advanced disease is based on symptomatic
      treatment and improvement of quality of life, correction of anaemia must also be
      considered as part of palliative care.

PMID- 16459672
TI  - [Value of new prostate cancer markers: alpha methylacyl CoA racemase (P504S) and
      p63].
AB  - The diagnosis of prostate cancer is based on histological examination of
      prostatic biopsies using histological criteria identified on standard stains. In
      certain lesions mimicking prostate cancer, the pathologist must perform
      immunohistochemical studies looking for loss of basal cells and antibodies
      directed against cytokeratin CK 903 (34bE12) or CK5/6, which sometimes give
      inconclusive results leading to a diagnosis of suspicious site. The discovery of
      overexpression of alpha-methylacyl CoA racemase in prostate cancer using a
      microarray technique has allowed the development and marketing of an antibody
      (P504S /AMACR) which, in combination with a new basal cell marker (p63), is a
      very valuable tool for the pathologist in the management of suspicious sites and
      cancers less than 1 mm in diameter detected on prostatic biopsies.

PMID- 16459673
TI  - [Potential therapeutic implications of EGF R/PDGF R signalling pathways in bone
      metastases of prostate cancer].
AB  - The finding that EGF receptor (Epidermal Growth Factor Receptor) and PDGF
      receptor (Platelet-Derived Growth Factor Receptor) are involved in bone
      metastases opens up new therapeutic prospects. This new approach should allow the
      development of new therapeutic agents: EGF R/HER2 inhibitors and PDGF R
      antagonists.

PMID- 16459674
TI  - [Preservation of erectile function and radical prostatectomy: what to expect in
      2005?].
AB  - The preservation of erectile function in patients undertaking radical
      prostatectomy was discussed in multiple studies. In this review article we will
      discuss the factors which influence the recovery of erections as well as the
      therapeutic modalities. In fact, four possibilities of prevention and treatment
      are currently available: (1) nerve sparing surgery, (2) nerve grafting, (3) nerve
      stimulation and (4) pharmacotherapy after surgery.

PMID- 16459675
TI  - [Morbidity of unilateral and bilateral laparoscopic adrenalectomy according to
      the indication. Report of a series of 100 consecutive cases].
AB  - INTRODUCTION: Laparoscopic adrenalectomy is the reference technique for the
      treatment of adrenal tumours. This retrospective study reports the experience of
      100 consecutive laparoscopic adrenalectomies, in order to assess its indications,
      the incision, the morbidity and to determine the limitations of this procedure.
      MATERIAL AND METHODS: Between April 1994 and June 2004, 100 laparoscopic
      adrenalectomies were performed in 92 patients via a transperitoneal (n = 93) or
      retroperitoneal (n = 7) approach, with 84 unilateral and 8 bilateral
      adrenalectomies. The mean age was 52 years. The operative and postoperative
      characteristics and the functional results were evaluated. RESULTS: The mean
      operating time was 112 min [70-175] via the retroperitoneal approach, 101 min [40
      215] via the transperitoneal approach, and 135 min [120-270] for bilateral
      adrenalectomies. The mean tumour diameter was 44 mm [10-120 mm]. The mean blood
      loss was 215 ml [0-1210 ml]. Ten patients were transfused. The mean hospital stay
      was 3 days. Histology revealed 25 Conn adenomas, 20 cortisol-secreting adenomas
      and Cushing syndrome, 22 phaeochromocytomas, 20 metastases, 2 adrenal cortical
      adenomas, and 11 incidentalomas. Conversion to "open" surgery were necessary for
      technical difficulties in 6% of cases. There were 7 minor postoperative
      complications (7%) and 4 late complications (4%) (deep vein thrombosis, effusion,
      2 local recurrences). Four patients in the group with secondary adrenal tumours
      were alive without recurrence 18, 20, 44 and 48 months after adrenalectomy.
      Antihypertensive treatment was stopped in 16 of the 25 patients operated for Conn
      adenoma. The mean follow-up was 31 months [5-98 months]. CONCLUSION: This
      technique has a low morbidity, requires minimal postoperative analgesia and a
      short hospitalisation. The retroperitoneal or transperitoneal approach must be
      chosen as a function of the patient's history and the surgeon's habits. Tumours
      larger than 8 cm can be resected, but with a higher morbidity. Laparoscopic
      adrenalectomy for malignant tumours is associated with higher morbidity.

PMID- 16459676
TI  - [Risks and benefits of total nephrectomy in elderly patients over the age of 80].
AB  - OBJECTIVE: There is currently no consensus concerning the age limit for the
      surgical management of kidney tumours and very limited data are available in the
      literature. The objective of this study was to evaluate the morbidity of renal
      cancer surgery in elderly patients in order to determine the benefit/risk
      balance. MATERIAL AND METHODS: A retrospective study was conducted in 157
      patients operated for kidney tumour in our department. Two groups were defined:
      one group of 40 patients over the age of 80 years and another group of 117
      patients under the age of 80 years at the time of surgery. The following elements
      were compared in the 2 groups: presence or absence of symptoms, general state
      (evaluated by the Eastern Cooperative Oncology Group score), associated
      comorbidities (evaluated by the American Society of Anesthesiologists score),
      preoperative haemoglobin and serum creatinine, histological examination of the
      tumour, medical and surgical complication rate, postoperative mortality, length
      of hospital stay and specific survival. RESULTS: Tumour characteristics were
      identical in each group except for the presence of distant metastases which were
      more frequent in the group of patients young than 80. Older patients had a
      significantly higher preoperative serum creatinine (p = 0.01), a higher ASA score
      (p = 0.001), a higher medical complication rate (p < 0.00001) and a higher
      mortality (p = 0.04). At the end of follow-up, the specific survival was
      comparable in the two groups (32.5% versus 40%). CONCLUSION: Tumour
      characteristics and specific survival after surgical management of kidney tumours
      are comparable in elderly patients and younger patients. The risks of
      complications and impaired renal function were higher in elderly patients
      undergoing total nephrectomy. Close surveillance as well as minimally invasive
      alternatives will probably have an increasingly important place in the future,
      especially in patients presenting a major surgical risk.

PMID- 16459677
TI  - [Treatment of inferior caliceal stones by flexible ureteroscopy].
AB  - OBJECTIVE: Evaluation of the treatment of inferior caliceal stones by flexible
      ureterorenoscopy and Holinium-YAG laser on a series of 69 operations. MATERIAL
      AND METHOD: Between April 1998 and December 2003, 69 flexible ureteroscopies were
      performed for 55 stones in 49 patients. The mean age of the patients was 51.6
      years (range: 18-78). The mean stone diameter was 12.8 mm (range: 5-3 1). 46% of
      stones had been pretreated by ESWL, PCNL or surgery. Endocorporeal lithotripsy
      was performed by Holmium-YAG laser in 45 cases, Lithoclast in 5 cases and en bloc
      extraction in 3 cases. Technical features, efficacy and morbidity were studied.
      The results were classified into fragment-free (FS), residual fragments (RF) < or
      = 4 mm, RF > 4 mm and failures. The results were evaluated on D0-D1 and at 3
      months on a plain abdominal x-ray and ultrasound. RESULTS: The mean operating
      time was 61 minutes (range: 25-120). Nine stones required several procedures. 20%
      of stones were cystine stones. A ureteric stent was placed in 67 cases. The mean
      length of stay was 2.5 days (D0-D8). At 3 months, after one or several
      ureteroscopies, the results were: 22% FS, 40% RF < or = 4 mm, 13% RF > 4 mm and
      25% failures. One half of failures occurred during the first 14 ureteroscopy
      procedures. There were 13 minor complications and no major complications.
      CONCLUSIONS: The results of flexible ureteroscopy in the treatment of inferior
      caliceal stones are encouraging, especially with standardization of the
      technique. It appears to be a good compromise between ESWL and PCNL, particularly
      for stones between 10 and 20 mm, cystine stones and after failure of reference
      techniques.

PMID- 16459678
TI  - [Ureterocalicostomy: indications and results based on a series of 16 patients].
AB  - Formerly considered to be a salvage or last resort technique before nephrectomy,
      ureterocalicostomy can be indicated in certain well defined situations, when
      strictly dependent drainage of urine is essential. Due to its particular
      indications, this procedure is rarely performed and operators have limited
      experience. The authors report 17 cases of ureterocalicostomy performed in 16
      patients: 8 cases obtained an excellent long-term result with absence of clinical
      signs, urinary tract infection and proximal dilatation of the neo-junction. 4
      cases obtained a good result with resolution of clinical symptoms and
      bacteriological signs and improvement of the dilatation on intravenous urography.
      3 cases obtained a poor result with persistence of clinical symptoms and
      dilatation on intravenous urography. 2 nephrectomies were subsequently performed
      4 years and 10 years after ureterocalicostomy for non-functioning kidney and for
      chronic pyelonephritis.

PMID- 16459679
TI  - [Ureterocalicostomy: last resort in the treatment of certain forms of
      ureteropelvic junction stenosis. Report of 5 cases].
AB  - INTRODUCTION: Iatrogenic stenoses of the ureteropelvic junction are now
      essentially treated by endoscopic techniques. However, conventional surgery is
      sometimes required to treat severe or extensive stenosis. The authors report the
      use of ureterocalicostomy to treat 5 patients with complex lesions. MATERIAL AND
      METHODS: Between 2001 and 2003, the authors treated five patients with iatrogenic
      stenosis of the ureteropelvic junction. Two of these patients had a history of
      percutaneous nephrolithotomy and the other three had undergone conventional
      pyelotomy, complicated by pyelocaliceal avulsion in one case. The diagnosis was
      confirmed by double anterograde and retrograde opacification in four patients and
      intravenous urography in one patient. It was decided to perform
      ureterocalicostomy due to the extent of the lesions. Inferior ureterocalicostomy
      was performed after lower pole nephrectomy in all cases. RESULTS: The mean follow
      up was 21 months (range: 20 to 27 months). Three patients had an uneventful
      postoperative course and satisfactory radiological follow-up. One patient rapidly
      developed stenosis that was treated successfully by endoscopy and another patient
      obtained a poor result requiring nephrectomy. CONCLUSION: Ureterocalicostomy
      requires laborious surgical dissection and meticulous ureterocaliceal
      anastomosis, but it is a useful technique in some cases of severe and extensive
      iatrogenic stenosis of the ureteropelvic junction.

PMID- 16459680
TI  - [Influence of urinary citrate levels on spontaneous calcium oxalate dihydrate
      crystalluria].
AB  - INTRODUCTION: Calcium oxalate is the leading cause of renal stones and is mainly
      due to hypercalciuria, hyperoxaluria and/or hypocitraturia. Citrate is considered
      to be an effective inhibitor of calcium oxalate crystallization and is therefore
      increasingly prescribed as maintenance therapy for patients with calcium stones,
      but no study has investigated the effect of urinary citrate levels on spontaneous
      calcium oxalate crystalluria in human urine. In this study, the authors examined
      the relationships between the calcium oxalate molar product, the urinary citrate
      concentration and weddellite (oxalate calcium dihydrate) crystalluria, the most
      frequent crystalline form of calcium oxalate in human urine. MATERIAL AND
      METHODS: Crystalluria analysis and calcium, oxalate and citrate assays were
      performed on a series of 10,222 first morning urine samples from 4,809 stone
      patients and 453 first morning urine samples from 317 control subjects. The
      frequency and characteristics of weddellite crystalluria were determined as a
      function of the calcium oxalate molar product (pCaOx) and urinary citrate
      concentration. RESULTS: 1,940 urine samples (18.2%) presented weddellite
      crystalluria, which was pure in 1,378 urine samples from stone patients (13.5%)
      and 43 urine samples (9.5%) from controls (p < 0.05). The crystalluria rate in
      stone patients ranged from 4% for pCaOx < 1 (mmol/l)2 to 81.3% for pCaOx > or = 3
      (mmol/l)2 (p < 0.0001). Over the same interval of pCaOx, weddellite crystalluria
      ranged from 1.5% to 72.2% in control subjects. An increase of urinary citrate
      excretion from 0.5 to 5 mmol/l significantly lowered the frequency of
      crystalluria from 32.4% to 10.1% for a pCaOx between 1 and 2 (mmol/l)2 (p <
      0.0001) and from 63% to 27.9% for a pCaOx between 2 and 3 (mmol/l)2 (p < 0.001).
      For pCaOx values > or = 3 (mmol/l)2, urinary citrate excretion no longer
      significantly influenced the frequency of crystalluria. The number of crystals
      and aggregates and the maximum dimensions of aggregates were only influenced by
      the urinary citrate concentration when the pCaOx product was < 2 (mmol/l)2.
      CONCLUSION: The main determinant of the frequency and characteristics of
      weddellite crystalluria is the pCaOx molar product. The beneficial effect of the
      urinary citrate concentration on the frequency of crystalluria is observed for
      pCaOx values < 3 (mmol/l)2, but only for pCaOx values < 2 (mmol/l)2 for the
      characteristics of crystalluria such as the number and dimensions of crystals and
      aggregates. This means that therapeutic measures designed to increase urinary
      citrate concentrations can only be effective when pCaOx has been previously
      lowered by increased diuresis or specific reduction of urinary calcium and/or
      urinary oxalate levels.

PMID- 16459681
TI  - [Comparative study of two latest generation flexible ureterorenoscopes].
AB  - INTRODUCTION AND OBJECTIVES: Miniaturization and development of flexible
      instruments have led to the development of flexible ureterorenoscopy. The
      objective of this study was to compare the capacities of active deflection of two
      latest generation flexible ureterorenoscopes and to evaluate alteration of
      deflection and flow of irrigating fluid in the presence of instruments in the
      operating channel. MATERIAL AND METHODS: Two ureterorenoscopes were evaluated in
      this study. The Karl STORZ Flex-X and the ACMI DUR-8 Elite. Comparison of
      deflection movements was performed ex situ by super-imposing all active movements
      of the two ureterorenoscopes. Alteration of deflection was performed by
      alternately placing an extraction or fragmentation instrument of variable
      dimensions in the operating channel. Alteration of flow was also assessed in the
      presence of the same instruments. RESULTS: The ex situ deflection capacities of
      the DUR-8 Elite flexible ureterorenoscope were more extensive than those of the
      Flex-X, but it was more complicated to manipulate. Alterations of deflection and
      flow of irrigation fluid were comparable for the two ureterorenoscopes.
      CONCLUSION: On the basis of these data, we can confirm that the two latest
      generation ureterorenoscopes present comparable capacities, but different
      functioning modalities. We therefore recommend that each operator test the two
      ureterorenoscopes to become familiar with their manipulation. Other studies are
      necessary to evaluate the optical properties, ease of use in clinical practice
      and fragility of these new ureterorenoscopes.

PMID- 16459682
TI  - [Endoscopic lithotripsy and FREDDY laser technology. Initial experience].
AB  - INTRODUCTION AND PURPOSE: FREDDY laser technology was developed for endocorporeal
      lithotripsy. The purpose of this study was to evaluate, based on our initial
      experience, the efficacy and place of this technology in the treatment of urinary
      calculi by ureterorenoscopy. (World of Medicine) to treat 26 patients (29 stones)
      by ureterorenoscopy. This was the second procedure for 25 stones: after ESWL (23
      cases) or percutaneous nephrolithotomy (2 cases) and the first procedure for 4
      stones. The mean stone diameter was 9 mm (range: 6-15 mm). Thirteen stones were
      situated in the kidney and 16 were in the ureter. Success of treatment was
      defined by the absence of residual fragments immediately after the operation or
      at one month on plain abdominal x-ray. RESULTS: Twenty-six stones were
      satisfactorily fragmented. At three months, 21 out of 26 (80.7%) patients were
      stone-free corresponding to 21 out of 29 (72.4%) stones). Failures concerned 8
      stones (5 patients). For five stones, measuring more than 10 mm, residual
      fragments persisted at three months. For three other stones, two cystine stones
      and one calcium oxalate monohydrate stone, fragmentation was insufficient or even
      nonexistent for the cystine stones. The mean length of hospital stay was 1.5 days
      (range: 1-3 days). A ureteric perforation due to a stone impacted in the ureteric
      wall was observed. CONCLUSIONS: FREDDY laser endoscopic lithotripsy is a safe and
      effective method due to the wavelength used. This laser could constitute an
      alternative treatment option in view of its moderate cost and the fact that it is
      adapted to flexible ureterorenoscopy. However, it presents certain limitations in
      terms of fragmentation, particularly in the case of cystine stones, and cannot be
      used to treat solid lesions (urinary tract strictures and tumours).

PMID- 16459683
TI  - [Treatment of patients with recurrent superficial bladder cancer with lyophilized
      Moureau-Rio de Janeiro BCG strain. Brazillian National Cancer Institute
      experience].
AB  - PURPOSE: We present our experience with lyophilized Moureau-Rio de Janeiro BCG
      strain for treatment of patients with recurrent superficial bladder cancer.
      PATIENTS AND METHODS: From October 1986 to January 2001, 114 patients were
      treated by transurethral resection followed by intravesical instillation of BCG
      at our institution. Follow-up ranged from 10 to 144 months (mean 50.16 months).
      The treatment included 6 inductions and 10 maintenance cycles of BCG
      instillations. The patients received an initial dose with 40 mg and subsequent
      doses with 80 mg of lyophilized Moureau-Rio de Janeiro BCG strain. Chi-square and
      Mantel-Haenszel test, with 95% significance, were used to evaluate possible
      associations among variables. The Kaplan-Meyer method was used to evaluate the
      disease-free survival rates while log-rank test was used to compare curves among
      the groups. RESULTS: Overall recurrence and progression rates after treatment
      were 45.6% and 13%, respectively. Four patients (3.5%) had complications
      following BCG instillations. Three of them had to be treated with antituberculous
      therapy. These patients presented pulmonary disease, granulomatous prostatitis
      and epididymo-orchitis respectively. CONCLUSIONS: Moureau-Rio de Janeiro BCG
      strain was overall well tolerated in intravesical instillations, similar to other
      strains used in literature. Recurrence rates were decreased with adjuvant BCG
      therapy. Tumor size, grade and presence of associated carcinoma in situ provided
      predictive information regarding the behavior of recurrent superficial tumors.
      The WHO/ISUP classification when compared with tumor grade was superior in
      selecting patients with high risk of progression.

PMID- 16459684
TI  - [Treatment of benign prostatic hyperplasia (BPH) by transurethral needle ablation
      (TUNA) and 36-month follow-up of the retreatment rate].
AB  - OBJECTIVE: Benign prostatic hyperplasia (BPH) is a disease affecting about 25% of
      men over the age of 40. One half of these men report symptoms that interfere with
      their daily activities. MATERIAL AND METHODS: In this multicentre study, 102
      patients with BPH were treated by transurethral needle ablation (TUNA). The
      efficacy of treatment was evaluated for 12 months after the operation by means of
      Madsen and IPSS (International Prostate Symptom Score) scores. The course of
      uroflowmetry and quality of life (International Score) and sexual function were
      also assessed for one year. The safety of treatment was evaluated according to
      the type and frequency of complications. The results show an immediate and
      significant improvement of symptoms (p < 0.0001 for Madsen and IPSS scores and
      maximum flow rate between M0 and M12) demonstrating the efficacy of the TUNA
      system. A very positive impact of TUNA was demonstrated on quality of life. No
      negative impact was reported on sexual function and the operation had very few
      repercussions with a low adverse event rate. The retreatment rate (surgical
      and/or drug) was evaluated 36 months after the operation by means of an optional
      follow-up questionnaire subsequently completed by the investigators. RESULTS:
      After 3 years, based on the 80 questionnaires returned, 43 patients (53.8%) were
      stable and did not need any other medical or surgical treatment for BPH. Thirty
      seven (37) patients (46.3%) required retreatment: 21 were treated with drugs
      (26%), 17 were treated surgically (21.25%) including 1 patient who was also
      retreated with drugs. This study demonstrates the significant and lasting
      improvement of BPH symptoms by TUNA, which constitutes an alternative attractive
      to surgery in young patients and/or patients worried about their sexuality.

PMID- 16459685
TI  - [Reasons for the choice of urology by residents].
AB  - OBJECTIVE: Due to the reduction of the potential number of residents in surgery,
      a study was conducted to determine the reasons motivating the choice of urology.
      MATERIAL AND METHODS: A questionnaire was sent to several generations of
      urologists concerning the criteria which influenced their choice of this surgical
      subspecialty. RESULTS: More than one half had chosen urology before their
      residency. Almost none of the urologists in this subgroup hesitated about another
      surgical subspecialty at the time of their final choice. Hospital medical
      training is therefore an essential factor in the choice of the future specialty.
      Almost all urologists who chose their specialty during their residency initially
      hesitated with another discipline, corresponding to gastrointestinal surgery in
      59% of cases. The most attractive feature was the medical and surgical aspect of
      urology and possibility of group practice with several urologists, limiting the
      time on call. CONCLUSIONS: Hospital medical students therefore constitute a
      potential reserve for urologists and need to be motivated by means of good
      quality practical teaching. Residents in other specialties can also modify their
      initial choice in favour of urology, especially gastrointestinal surgeons.

PMID- 16459686
TI  - [Haemostatic efficacy of a high intensity focused ultrasound applicator in lower
      pole partial nephrectomy in the pig].
AB  - OBJECTIVE: To evaluate the haemostatic property of a high intensity focused
      ultrasound (HIFU) applicator in lower pole partial nephrectomy in a porcine
      model. MATERIALS AND METHODS: An applicator with a flat HIFU transducer operating
      at a frequency of 3.78 MHz was designed. Nine female pigs weighing between 35 and
      39 kg were used. The kidneys of 5 pigs were used to characterize basic lesions,
      study haemostatic efficacy and measure the temperature rise in treated tissues.
      The following 4 pigs were treated by HIFU prior to bilateral lower pole partial
      nephrectomy. Treatment consisted of circumferential juxtaposition of basic
      lesions in the lower pole with vascular clamping. Haemostatic efficacy was
      evaluated immediately and 30 minutes after lower pole resection. RESULTS: A 50
      second ultrasound pulse with an intensity of 26 W/cm2 induced a full thickness
      lesion of the kidney, between 22 and 36 mm. Lesions were reproducible. The
      temperature rise observed in treated tissues was 62 +/- 12, 59 +/- 9 and 58 +/-
      11 degrees C at distances of 15, 20 and 25 mm from the transducer, respectively.
      All lower pole partial nephrectomies were exsanguinated, except for one case
      (12.5%), in which a central renal artery was not controlled. CONCLUSIONS: Our
      HIFU applicator is an excellent haemostatic tool ensuring effective coagulation
      of the renal parenchyma, allowing dry lower pole partial nephrectomy. Improvement
      of the ergonomics of this applicator and adaptation to laparoscopy are currently
      under investigation.

PMID- 16459687
TI  - [Place of duloxetine in the treatment of stress urinary incontinence].
AB  - Urinary incontinence is a public health problem, as more than three million women
      in France are concerned by this problem. The prevalence of stress urinary
      incontinence is about 40% among these women. Duloxetine is a molecule developed
      for the oral treatment of stress urinary incontinence. It is a serotonin and
      norepinephrine reuptake inhibitor, which acts by increasing urethral sphincter
      tone. In several phase III trials, duloxetine administered orally at a high dose
      of 80 mg per day, significantly reduced episodes of incontinence. Total scores on
      the Incontinence Quality of Life questionnaire (I-QOL) were more markedly
      improved by duloxetine than by placebo. Nausea was an adverse effect observed in
      more than 25% of cases and required discontinuation of treatment in some
      patients. However, the encouraging preliminary results of duloxetine in this
      indication must be confirmed during phase IV post-marketing clinical trials.

PMID- 16459688
TI  - [Anatomy of obturated foramen. Application to trans-obturator slings].
AB  - The development of the trans-obturator sling in the treatment of female
      incontinence created a renewal of interest for the study of the anatomy of the
      obturator region, as shows the recent anatomical studies published on the
      subject. The objective being to consider the risks of bladder and vasculo-nervous
      injuries of this new way. The risk of wound of the bladder is small as concerns
      this technique of the mode of insetion of the sling (outside inside or inside
      outside) because the sling is in a strictly perineal way. The risk of damage
      caused in the vasculo-nervous elements of the obturator region is weak
      considering the position of the sling with regard to the main pedicles. These are
      either for distance of the sling for the obturator and femoral vessels and the
      saphenous vein, or protected by the obturator bone frame for the pudendal pedicle
      and the anterior branch of the obturator artery, or they are reduced to the state
      of capillaries or nerve ending. The trans-obturator sling presents the advantage
      to allow a strictly perineal, horizontal situation of the sling, which restores
      the system of a natural sub-urethral vaginal sling, avoiding complications due to
      the penetration of the Retzius space and of the pelvian cavity.

PMID- 16459689
TI  - [Transobturator surgery for female urinary continence: from outside to inside or
      from inside to outside: a comparative anatomic study].
AB  - OBJECTIVE: Transobturator route is now largely used for the positioning of the
      supporting sub uretral tape in the surgical treatment of female urinary
      incontinence. This operation can be done using the original technique from the
      outside to the inside or by inside to outside. Our anatomic study evaluates the
      specific dangers of each MATERIAL AND METHODS: Our study is based on the
      dissection of seven fresh bodies, therefore 14 obturator regions. The dissections
      were done after the positioning of the tape from outside to inside on one side
      and inside to outside on the other side. We particularly studied the distances
      separating the tape from the inferior pudendal vascular bundle and the posterior
      branch of the obturator nerve. RESULTS: With the inside - outside technique there
      is a greater proximity between the path of the tape and the studied structures,
      therefore the risk of damage is greater. CONCLUSIONS: The two techniques are not
      equivalent. There are less vascular and neurological risk using the original
      outside to inside technique.

PMID- 16459690
TI  - [Management of serious infectious complications of transobturator suburethral
      tape: report of 2 cases].
AB  - Suburethral TVT tape has become immensely popular since its invention in 1995. A
      new transobturator surgical approach was proposed in 2001, resulting in a
      modification of the quality of the tape available from various suppliers. The
      authors present 2 cases of obturator foramen abscess related to suburethral
      Uratape, occurring a long time after the procedure and requiring complete removal
      of the tape. These infections can be prevented by using good quality tape, which
      must be made from monofilament large-mesh woven polypropylene. The tape must be
      completely removed as early as possible in the case of vaginal erosion, even
      asymptomatic, via a transobturator approach, if necessary.

PMID- 16459691
TI  - [Women faced with the problem of erectile dysfunction: women's view on a male
      problem].
AB  - MATERIAL AND METHODS: This study is based on an opinion survey conducted with the
      support of the Societe d'Etudes Francaise Louis Harris, performed by telephone on
      a final sample of 507 women, representative of the population of French women
      between the ages of 20 and 65 years, interviewed about their sexuality. In
      particular we studied their perception and behaviour in relation to their
      partner's erection problems. RESULTS: 25% of women reported that they had
      experienced such problems, and although it was impossible to define a predictive
      profile pre-disposing to this problem, their attitude in relation to this event
      was found to be globally positive with an attitude designed to reassure and
      stimulate the partner experiencing erectile dysfunction (92%). In contrast, 66.4%
      of women considered that their partner's attitude tended to reinforce their
      sexual difficulties (insistence, withdrawal, avoidance, absence of dialogue).
      Erectile dysfunction (ED) does not affect the sexual satisfaction of the partner
      concerned (satisfied in 84% of cases), who report that they suffer much more from
      the lack of communication, frequent in this type of situation, well than from the
      absence of penetration (3%). CONCLUSION: Medical consultation is still relatively
      rare, and is essentially requested by the woman when her partner withdraws and
      refuses any assistance. It is often prevented by negative cognitions concerning
      the irreversibility of ED, for example when it is attributed to age. There is
      also a significant difference between women who say that they would encourage
      their partner to consult for this type of problem (87%), and those who actually
      encourage their partner to consult when specifically faced with this problem
      (8%). Women faced with the problem of ED are largely more in favour of the use of
      erectile drugs that those of the other group.

PMID- 16459693
TI  - [Unusual metastatic spread after converted laparoscopic radical nephrectomy:
      natural history of the tumour or role of laparoscopy?].
AB  - Retroperitoneal or transperitoneal laparoscopic radical nephrectomy is currently
      proposed by an increasing number of urologists as an alternative to conventional
      open surgery to treat renal tumours. The authors report a case of metastasis to
      unusual sites (sigmoid colon, small intestine, root of the nose) after converted
      retroperitoneal laparoscopic radical nephrectomy for a T3 renal tumour, which
      raises the problem of the possible role of the laparoscopic approach in this
      unusual metastatic progression of the disease.

PMID- 16459694
TI  - [Retroperitoneal Castleman disease].
AB  - Castleman disease or angiofollicular lymph node hyperplasia is a rare disease of
      unknown cause with polymorphic clinical features that raises many diagnostic and
      therapeutic problems. The unifocal, localized, pseudoneoplastic form, first
      described in 1956, has a good prognosis, but the multifocal form has a more
      aggressive course. Three histological types have been identified: hyaline
      vascular, plasma cell and mixed. The authors present a case of hyaline vascular
      unifocal Castleman disease. A retroperitoneal mass was discovered incidentally
      during follow-up ultrasound examination in a 38-year-old woman treated for
      recurrent renal stones. On CT examination, a solid mass measuring 9 x 8 x 6 cm
      raised a problem of differential diagnosis with other retroperitoneal masses. CT
      guided biopsy was inconclusive and the diagnosis was finally established by
      tumour excision and histological examination. The immediate and subsequent
      postoperative course was uneventful.

PMID- 16459695
TI  - [Appendicular ureteroplasty to repair a ureteric lesion during disk surgery].
AB  - Extensive ureteric lesions raise difficult problems of surgical repair. This is
      also the case for upper ureteric lesions that often require replacement of the
      damaged segment or even autologous transplantation. The authors report a case of
      iatrogenic ureteric lesion resulting in a large defect in a patient operated 6
      months previously for an L4-L5 disk hernia, which was treated successfully by
      interposition of an appendicular graft between the two ureteric stumps. In the
      light of this case, the authors discuss the various appearances of iatrogenic
      ureteric lesions with particular emphasis on the value of appendicular
      ureteroplasty due to its simplicity and low morbidity, while waiting for progress
      in the field of biocompatible substitutes.

PMID- 16459696
TI  - [Nested variant urothelial carcinoma: diagnostic difficulties].
AB  - Nested variant urothelial carcinoma is a recently identified variant of
      urothelial carcinoma which is difficult to diagnose due to its resemblance to
      other benign bladder lesions, such as hyperplasia of Von Brunn nests. The authors
      present three clinical cases of this variant of urothelial carcinoma and
      emphasize the importance of clinical, cytological, histological and
      immunohistochemical criteria for the diagnosis and the need for early and adapted
      therapeutic management, as this type of bladder tumour, wrongly considered to be
      benign up until the early 1990s, is just as invasive as high-grade urothelial
      carcinoma.

PMID- 16459698
TI  - [Genital sites of Buruli ulcer (BU): clinical and therapeutic aspects].
AB  - BU of the penis and scrotum is a rare disease that can potentially induce
      extensive lesions. The authors describe the clinical characteristics and
      treatment in the light of two cases. BU induces irreversible necrotic lesions and
      despite the knowledge of the micro-organism responsible (Mycobacterium ulcerans),
      no medical treatment is currently effective. Excision of wounds and skin grafts
      remain the treatment of choice, and give excellent results.

PMID- 16459697
TI  - [Epidural abscess after prostatic biopsies].
AB  - Prostatic biopsy is a routine clinical procedure often wrongly considered to be
      perfectly harmless. The authors report the first case of epidural abscess after
      prostatic biopsy, despite properly conducted antibiotic prophylaxis. Although the
      epidural space is a known site of infection, the relationship with prostatic
      biopsies has never been previously reported. This clinical case emphasizes the
      need for complete patient information and the importance of anti-infective
      prophylaxis guidelines.

PMID- 16459699
TI  - [Paratesticular fibrous pseudotumours].
AB  - Paratesticular fibrous pseudotumours are a rare form of benign tumour with a slow
      course and a difficult preoperative diagnosis. The objective of treatment is to
      ensure optimal testis conservation, which is possible when the diagnosis is made
      on intraoperative frozen section examination. The authors report a case of
      diffuse fibrous pseudotumour in a 23-year-old man. In the light of this case and
      a review of the literature, they discuss the diagnostic and therapeutic aspects
      of these tumours.

PMID- 16459700
TI  - [Penile fracture: report of 4 cases].
AB  - OBJECTIVE: To inform practitioners about this rare condition and to emphasize the
      importance of surgical treatment. MATERIAL AND METHODS: Four patients were
      treated for penile fracture, by surgery in 3 cases and medically in 1 case.
      Surgery consisted of a longitudinal elective incision, followed by evacuation of
      the haematoma and suture of the tunica albuginea. RESULTS: These patients were
      aged between 19 and 42 years; 3 were single and 1 was married. The mechanisms of
      fracture were coital injury in 2 cases and masturbation in 2 cases. In the 3
      operated patients, all lesions were transverse sections of the tunica albuginea.
      A good functional result was obtained in operated patients, but could not be
      evaluated in the medically treated patient. CONCLUSION: The best treatment for
      penile fracture is surgery after a clinical diagnosis.

PMID- 16459701
TI  - [Glans reimplantation after circumcision accident].
AB  - INTRODUCTION: Circumcision, the most frequent operation in boys, is performed by
      various persons and is responsible for a considerable number of documented or non
      documented complications. CASE REPORT: The authors report a case of accidental
      traumatic amputation of the glans during ritual circumcision performed by a nurse
      on a 5-year-old boy. Reimplantation was successfully performed after suture of
      the glans. In the light of this case and a review of the literature, the authors
      describe the treatment and prevention of this type of lesion. CONCLUSION:
      Circumcision is not a completely benign operation. Iatrogenic lesions are
      frequent but rarely serious. The best treatment is prevention, which requires
      education of the population about the importance of medicalized circumcision.

PMID- 16459702
TI  - [One-stage laparoscopic bilateral cutaneous ureterostomy].
AB  - Laparoscopic cutaneous ureterostomy is an alternative to definitive percutaneous
      nephrostomy for patients with pelvic malignancies. The surgical technique was
      initially described by lumbar laparoscopy, requiring a change of position in the
      case of a bilateral procedure. The authors describe a laparoscopic technique
      allowing bilateral cutaneous ureterostomy to be performed without a change of
      position.

PMID- 16459703
TI  - [Laparoscopic sacral colpopexy: comparison of nonresorbable prosthetic tape
      (Mersuture) and a SIS collagen matrix (Surgisis ES)].
AB  - OBJECTIVE: Surgical repair of pelvic prolapse by sacral colpopexy classically
      uses nonresorbable prosthetic tape. Infectious or erosive complications can
      sometimes occur and are often difficult to treat. The authors propose the use of
      a xenogeneic biomaterial composed of an extracellular collagen matrix: SIS (Small
      Intestinal Submucosa). MATERIAL AND METHODS: Fifty seven laparoscopic sacral
      colpopexies were performed between November 2001 and December 2003: 14 using SIS
      tape (anterior + posterior in 13 cases, anterior only in 1 case) and 43 using
      Mersuture PETP nonresorbable tape (anterior + posterior in 31 cases, anterior
      only in 10 cases and posterior only in 2 cases). Suburethral support was
      associated with sacral colpopexy in 40 patients with stress urinary incontinence.
      RESULTS: With a mean follow-up of 15.3 months (range: 3-24 months), one case of
      recurrent prolapse was observed after 7 months in the SIS group. For the PETP
      group (mean follow-up: 14.6 months, range: 5-25 months) 3 cases of recurrent
      prolapse were observed at the third postoperative month. Two cases of refractory
      constipation were observed in the PETP group versus one in the SIS group. The
      mean operating time was 100 (1 tape) and 120 minutes (2 tapes) with difference
      according to the type of material. The mean hospital stay was 4.8 days. No
      infectious complication was observed in either group. CONCLUSION: These
      encouraging results suggest that SIS can constitute an alternative to
      nonresorbable tape in sacral colpopexy. It appears to be well tolerated in the
      medium-term. The functional characteristics of SIS, replaced within 6 months by
      newly formed connective tissue, suggest a lower long-term risk of infection and
      erosion.

PMID- 16459704
TI  - [Evaluation of the Global Abdominal Method (ABDO-MG) in the treatment of urinary
      incontinence].
AB  - AIMS OF STUDY: Assessment of the Abdominal Global Method (ABDO-MG) in the
      treatment of stress urinary incontinence or mixed incontinence with stress
      predominance in women. METHODS: Thirty patients with clinically and
      urodynamically proven genuine stress incontinence or mixed incontinence with
      stress predominance were enrolled. Patients had 4 weeks of ABDO-MG technique
      under supervision and a home unit to do their exercises, then 8 weeks of home
      exercises without home unit or supervision. We compared the results for each
      patient before the treatment, at 4 and 12 weeks post initiation of the technique.
      Main outcome measures were short Pad test with standardized bladder volume and
      exercises as well as self-report of degrees of incontinence. RESULTS: The data
      showed improvement in leakage on short Pad test from 82.0 g before versus 38.8 g
      and 24.8 g at 4 and 12 weeks respectively (p = 0.0002). Seventeen of thirty
      patients were completely dry. All patients reported improvement of their
      condition after 4 weeks of exercises and almost cure at 12 weeks (p = 0.0001).
      CONCLUSIONS: This is the first study demonstrating the clinical efficacy, both
      objectively and subjectively, of the technique ABDO-MG in the treatment of
      genuine stress urinary incontinence and mixed incontinence with stress
      predominance in women. Our data are encouraging, however long-term study with
      control group is warranted.

PMID- 16459706
TI  - What is the purpose of a risk assessment?

PMID- 16459705
TI  - [The beneficial effect of mineral waters of Fiuggi on Pope Bonifacio VIII and
      Michelangelo: two prominent calculous patients].
AB  - Going back to the dawn of time, we deal with two historical figures, that of Pope
      Bonifacio VIII, and that of the hierophant of art, Michelangelo Buonarroti. The
      texts and the codes of the British Museum (Department of Manuscripts), of the
      Biblioteca Medica Laurenziana (Archivio Buonarroti) of Florence, and the
      Biblioteca Apostolica of Vatican, convincing detalled evidence that both figures
      were urological patients. It concerns two clinical cases with especially pertain
      to the history of lithiasis of urinary tract. Even though, both of them--the
      first with nephrolithiasis or gravel, and the second with a bladder stone--were
      historically bound with the well-known cures of Fiuggi in Italy.

PMID- 16459707
TI  - An evaluation of the US Environmental Protection Agency definition of a risk
      assessment.
AB  - A full presentation of relevant information, including both non-adverse and
      beneficial effects, of chemicals is important to developing sound and balanced
      risk assessments. Such considerations are not new. For example, the American
      Thoracic Society has developed criteria for defining adverse and non-adverse
      pulmonary effects. Failing to allow risk assessors to even consider non-adverse
      and beneficial effects will discourage the use of information from developing
      technologies, such as genomics, and from new understandings of dose-response
      relationships, as reflected in the hormetic model. Failing to provide such
      information to risk managers potentially provides a biased perspective on risk.

PMID- 16459708
TI  - The case for integrating low dose, beneficial responses into US EPA risk
      assessments.
AB  - When conducting risk assessments, the US Environmental Protection Agency (EPA)
      does not currently consider the beneficial effects from exposure to
      concentrations of agents below the no observed adverse effect level (NOAEL). If
      such benefits were observed, and if the beneficial and toxicological mechanisms
      of action were identical, this would probably be represented as a 'j-shaped'
      hormetic dose-response curve. If such data are available, they should be
      considered when assigning uncertainty factors for safe exposure calculations.
      However, when such data are not readily available, as is likely the case when the
      mechanism of action of the benefit differs from that of toxicity, current US EPA
      methods appear adequate.

PMID- 16459709
TI  - The issue of risk in complex adaptive systems: the case of low-dose radiation
      induced cancer.
AB  - Living systems exist in hierarchical levels of biological organization, ascending
      from the basic atomic-molecular level, to the cellular level, the tissue-organ
      level, and the whole organism. All levels and elements at each level communicate
      with each other though intricate intra- and intercellular signaling through many
      specified molecular interactions. These regulate homeostasis between the system
      levels and their individual elements. The probability of a defined effect at the
      basic atomic-molecular level per impact increment of a toxic agent, such as
      ionizing radiation, at that level appears constant at low doses, even if the
      probability constant may change as a consequence of a previous exposure. Thus, at
      a given state of the system, the incidence of effect at the atomic-molecular
      level increases linearly with the number of impact increments in terms of energy
      deposition events. Primary effects may amplify to damage and there are immediate
      attempts at repairing the damage from an effect. Amplification and propagation of
      damage at, and from, the basic to higher levels of biological organization meets
      resistance, the degree of which per impact increment is not constant. It changes
      with the number of impact increments. This resistance encompasses both physico
      chemical and biochemical reactions. The corresponding biochemical reactions
      express the physiological system's capacity to respond to perturbations of
      homeostasis at and between the various levels. Types and degrees of these
      responses depend on the system and the degree of homeostatic perturbation. At
      relatively mild to moderate degrees of perturbation, protective responses appear
      with a delay of hours and may last for months, shield also against endogenous non
      radiogenic damage, and in doing so may prevail over radiogenic damage. With
      increasing degrees of homeostatic perturbation, damage eventually overwhelms
      adaptive protection. Thus, systems do not respond in a linear function of impact
      increments at the lowest level of biological organization. For assessing the
      probability of radiation damage per absorbed dose, i.e., risk, in complex
      adaptive systems, both damaging and protecting responses need attention, and to
      exclude one for the other is scientifically unjustified and misleading.

PMID- 16459710
TI  - An examination of the Environmental Protection Agency risk assessment principles
      and practices: a brief commentary on section 4.1.3 of the EPA March 2004 Staff
      Paper.
AB  - The US Environmental Protection Agency (EPA) recently issued a Staff Paper that
      articulates current risk assessment practices. In section 4.1.3, EPA states, "...
      effects that appear to be adaptive, non-adverse, or beneficial may not be
      mentioned." This statement may be perceived as precluding risk assessments based
      on non-default risk models, including the hormetic--or biphasic--dose-response
      model. This commentary examines several potential interpretations of this
      statement and the anticipated impact of ignoring hormesis, if present, in light
      of necessary conservatism for protecting human and environmental health, and the
      potential for employing alternative risk assessment approaches.

PMID- 16459711
TI  - Examining the risks and benefits of considering both the traditional dose-
      response and hormesis in arriving at an acceptable exposure level.
AB  - In examining traditional dose-response and hormesis, we have considered the case
      examples of pulmonary hyperplasia following inhalation of carbon black and
      pulmonary hyperplasia after methyleneindolenine (3MEIN) exposures, development of
      irreversible pulmonary fibrosis, effect of continuous exercise and low-level lead
      exposures, and colorectal cancer. Adaptation can be used to estimate conventional
      dose responses. All cases discussed provided increased information about the
      reactions if hormetic features were included. In only the shigatoxin case was
      there clear irrefutable evidence that beneficial hormetic properties exist and
      must be considered; however, the one-in-six advantage is too great to ignore the
      potential benefits of hormesis. We recommend such hormetic properties be
      considered together with conventional dose responses to improve estimates of
      chemical risk.

PMID- 16459713
TI  - Comments on the Environmental Protection Agency's definition of risk assessment.
AB  - Common sense requires that regulation to prevent the adverse effects of exposure
      to chemicals should when possible preserve the desirable or beneficial effects of
      exposure to the chemical. Excluding such effects by definition is contrary to
      good science and common sense.

PMID- 16459712
TI  - Science-policy in environmental and health risk assessment: if we cannot do
      without, can we do better?
AB  - How can empirical evidence of adverse effects from exposure to noxious agents,
      which is often incomplete and uncertain, be used most appropriately to protect
      human health? We examine several important questions on the best uses of
      empirical evidence in regulatory risk management decision-making raised by the US
      Environmental Protection Agency (EPA)'s science-policy concerning uncertainty and
      variability in human health risk assessment. In our view, the US EPA (and other
      agencies that have adopted similar views of risk management) can often improve
      decision-making by decreasing reliance on default values and assumptions,
      particularly when causation is uncertain. This can be achieved by more fully
      exploiting decision-theoretic methods and criteria that explicitly account for
      uncertain, possibly conflicting scientific beliefs and that can be fully studied
      by advocates and adversaries of a policy choice, in administrative decision
      making involving risk assessment. The substitution of decision-theoretic
      frameworks for default assumption-driven policies also allows stakeholder
      attitudes toward risk to be incorporated into policy debates, so that the public
      and risk managers can more explicitly identify the roles of risk-aversion or
      other attitudes toward risk and uncertainty in policy recommendations. Decision
      theory provides a sound scientific way explicitly to account for new knowledge
      and its effects on eventual policy choices. Although these improvements can
      complicate regulatory analyses, simplifying default assumptions can create
      substantial costs to society and can prematurely cut off consideration of new
      scientific insights (e.g., possible beneficial health effects from exposure to
      sufficiently low 'hormetic' doses of some agents). In many cases, the
      administrative burden of applying decision-analytic methods is likely to be more
      than offset by improved effectiveness of regulations in achieving desired goals.
      Because many foreign jurisdictions adopt US EPA reasoning and methods of risk
      analysis, it may be especially valuable to incorporate decision-theoretic
      principles that transcend local differences among jurisdictions.

PMID- 16459714
TI  - Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally
      associated to clinical and MRI activity in patients with multiple sclerosis.
AB  - The aim of this study was to provide further insight into the effective
      contribution of classical soluble HLA-A, B and C class Ia (sHLA-I) and non
      classical soluble HLA-G class Ib (sHLA-G) molecules in immune dysregulation
      occurring in multiple sclerosis (MS). We evaluated by enzyme-linked immunosorbent
      assay (ELISA) technique intrathecal synthesis and cerebrospinal fluid (CSF) and
      serum levels of sHLA-I and sHLA-G in 69 relapsing-remitting (RR), 21 secondary
      progressive (SP) and 13 primary progressive (PP) MS patients stratified according
      to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We
      also tested, as neurological controls, 91 patients with other inflammatory
      neurological disorders (OIND) and 92 with non-inflammatory neurological disorders
      (NIND). Eighty-two healthy volunteers served as further controls for sHLA-I and
      sHLA-G determinations. An intrathecal production of sHLA-I and sHLA-G detected by
      specific indexes was significantly more frequent in MS patients than in controls
      (P<0.01). An intrathecal synthesis of sHLA-I was prevalent in clinically (P<0.02)
      and MRI active (P<0.001) MS, whereas a CSF-restricted release of sHLA-G
      predominated in clinically (P<0.01) and MRI stable (P<0.001) MS. sHLA-I levels
      were low in the serum of clinically active (P<0.001) and high in the CSF of MRI
      active (P<0.01) MS. Conversely, sHLA-G concentrations were decreased in the serum
      of clinically stable MS (P<0.01) and increased in the CSF of MRI inactive MS
      (P<0.001). The trends towards a negative correlation observed between CSF and
      serum concentrations and intrathecal synthesis of sHLA-I and sHLA-G in patients
      without evidence of clinical and MRI activity confirmed that intrathecal
      production and fluctuations in CSF and serum concentrations of sHLA-I and sHLA-G
      were reciprocal in MS. Our results suggest that, in MS, a balance between
      classical sHLA-I and non-classical sHLA-G products modulating both MRI and
      clinical disease activity in opposite directions may exist.

PMID- 16459715
TI  - No association of apolipoprotein E epsilon4 genotype with faster progression or
      less recovery of relapses in a Spanish cohort of multiple sclerosis.
AB  - BACKGROUND: Recent data have suggested a faster deterioration of multiple
      sclerosis (MS) patients who harbour the epsilon4 allele of the apolipoprotein E
      (APOE) gene. We investigate the relationship of APOE genotypes with disease
      severity and clinical recovery of relapses in a MS population of the north of
      Spain. METHODS: One hundred and thirty-three patients with clinically defined MS
      were studied. Disease course (relapsing versus progressive), age of onset,
      duration of the disease and disability measured by the Expanded Disability Status
      Scale (EDSS) were recorded. Worsening was measured by the Progression Index (PI)
      and by EDSS 4 and 6 latencies. In 79 patients with relapsing-remitting (RR) MS
      the degree of clinical recovery of relapses (total versus partial) was assessed.
      RESULTS: The frequency of the APOE epsilon4 allele in our patients was similar to
      that found in other southern European populations. APOE epsilon4 patients did not
      have a faster progression as assessed by PI and EDSS 4 and 6 latencies. Among 79
      patients with RRMS there were no significant differences in the degree of
      recovery of relapses. CONCLUSIONS: In this MS population, APOE epsilon4
      polymorphism is not associated with a more severe clinical course and does not
      appear to influence recovery of exacerbations.

PMID- 16459716
TI  - HLA-dPB1*0501 is not uniquely associated with opticospinal multiple sclerosis in
      Japanese patients. Important role of DPB1*0301.
AB  - Apart from its unique lesion distribution pattern, the opticospinal form of
      multiple sclerosis (OSMS) is distinct among Japanese patients who satisfy the
      diagnostic criteria of MS. OSMS has been suggested to be strongly associated with
      HLA-DPB1*0501 in Japanese. However, association of DPB1*0301 with non-OSMS and
      lack of DPB1*0301 in OSMS were also reported. To verify the role of DPB1*0501 and
      DPB1*0301 in Japanese MS patients we determined the frequencies of these alleles
      in 26 patients with OSMS, 167 with non-OSMS and 156 normal subjects, who were all
      residents of Hokkaido, the northernmost island of Japan. All (100%) OSMS were
      negative for DPB1*0301 while 32 (19%) of the non-OSMS were positive for the
      allele. In DPB1*0301-negatives, the frequencies of DPB1*0501 in OSMS (85%) and
      non-OSMS (82%) were similar, but both were higher than in the controls (66%). In
      DPB1*0301-positives, the frequency of DPB1*0501 was low but similar in non-OSMS
      (12/32; 38%) and controls (6/14; 43%). Periventricular white matter lesions (PVL)
      were noted in 31 of 32 (97%) DPB1*0301-positive non-OSMS patients but in only 22
      out of 135 (16%) DPB1*0301-negative non-OSMS patients and two out of 26 (8%) OSMS
      patients. Our findings indicate that DPB1*0501 plays an important role in the
      development of MS in general, but not in OSMS. The strong association of
      DPB1*0501 with OSMS may be due to the over-representation of the DPB1*0301 allele
      among individuals in the non-OSMS group. In addition, DPB1*0301 might be relevant
      to the development of periventricular lesions in Japanese patients with MS.

PMID- 16459717
TI  - The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample
      characteristics.
AB  - The Sonya Slifka Longitudinal Multiple Sclerosis Study follows a population-based
      cohort of approximately 2000 people with multiple sclerosis (MS) to study
      demographic and clinical characteristics, course of illness, utilization and cost
      of health services, provider characteristics, use of MS specialists and disease
      modifying agents, and neurologic, economic and psychosocial outcomes. This report
      describes the study methodology, presents baseline demographic and clinical data,
      and evaluates the representativeness of the sample. A stratified random sample of
      persons with established and recently-diagnosed MS selected from the National
      Multiple Sclerosis Society (NMSS) mailing lists was supplemented with recently
      diagnosed patients recruited through systematic nationwide outreach. Baseline
      data were collected by computer-assisted telephone interviews derived from
      standardized instruments; data collection continues at six-month intervals. The
      cohort was comparable to population-based and clinical samples with respect to
      demographics, course, relapse rate, symptoms, and severity of disability. Almost
      two-thirds of the cohort needed help with activities of daily living, three
      quarters were limited in work or other activities, and half had emotional
      problems that compromised quality of life. The Slifka Study cohort is broadly
      representative of the MS population and the database can be used to address
      questions not answered by natural history studies, clinical databases, or
      population-based surveys.

PMID- 16459718
TI  - Measuring and evaluating interferon beta-induced antibodies in patients with
      multiple sclerosis.
AB  - Administration of interferons (IFNs) may induce antibodies that interfere with
      therapeutic efficacy. We have optimized and validated methods for large-scale
      economic screening. Sera from patients with relapsing-remitting multiple
      sclerosis (MS) were investigated for binding antibody (BAb) by protein-G affinity
      chromatography radioimmunoassay and a commercially available enzyme immunoassay
      (EIA). Neutralizing antibody (NAb) was investigated by cytopathic effect assays
      (CEA) using both fixed amount and serially diluted sera. BAb correlated with
      log10-transformed titres obtained by EIA (r=0.70, P<0.0001); the latter, however,
      failed to demonstrate low-level BAb. Comparison of clinical significance of NAb
      positivity measured by biological assays with different sensitivities
      demonstrated an optimal odds ratio for relapse rate using 10 laboratory units
      (LU)/mL. Purification of IgG prior to CEA removed toxicity from toxic sera. The
      neutralizing capacity data correlated linearly with logl0-transformed titres
      obtained by a Kawade 10-to-1 LU/mL CEA (r=0.77, P<0.0001). In conclusion,
      neutralizing capacity CEA utilizing a fixed amount of serum predicts differences
      in relapse rates in IFNbeta-treated MS patients and correlates with NAb titres of
      the 10-to-1 LU/mL CEA. Neutralizing capacity CEA is less laborious and more
      economical than titre-based NAb assays and suitable for large-scale screenings of
      MS patients.

PMID- 16459719
TI  - Biological markers of interferon-beta therapy: comparison among interferon
      stimulated genes MxA, TRAIL and XAF-1.
AB  - Biological activity of interferon-beta (IFNbeta) can be assessed by measuring IFN
      stimulated genes (ISGs). Among them, myxovirus resistance protein A (MxA) appears
      to have the highest specificity, but it has no role in the pathogenesis of
      multiple sclerosis (MS). To investigate the reliability of MxA as a biomarker, we
      compared its expression to that of two other ISGs: TNF-related apoptosis-inducing
      ligand (TRAIL) and X-linked inhibitor of apoptosis factor-1 (XAF-1). Both were
      shown to be involved in immunoregulatory mechanisms and might play a role in MS.
      Quantitative-PCR measurements were performed in peripheral blood mononuclear
      cells from 73 MS patients after short-term and long-term treatment with IFNbeta.
      A time-dependent response for multiple ISGs was observed in all patients after
      short-term treatment. In contrast, long-term treatment induced concurrent
      inhibition of ISGs in 12.3% (9/73) of patients, in whom neutralizing antibodies
      (NAbs) were detectable. Besides, 22% (16/73) of chronically treated patients
      showed a non-NAbs-related abrogation of TRAIL expression. In summary, 1) MxA
      expression was significantly higher than both TRAIL and XAF-1, and 2) MxA was the
      most sensitive gene to detect decreased bioavailability due to NAbs. These
      findings identify MxA as an appropriate biomarker for IFNbeta, although there is
      no evidence for a functional role of it in MS.

PMID- 16459720
TI  - Early abnormalities of evoked potentials and future disability in patients with
      multiple sclerosis.
AB  - Evoked potentials (EP) have a role in making the diagnosis of multiple sclerosis
      (MS) but their implication for predicting the future disease course in MS is
      under debate. EP data of 94 MS patients examined at first presentation, and after
      five and ten years were retrospectively analysed. Patients were divided into two
      groups in relation to the prior duration of disease at the time point of first
      examination: group 1 patients (n=44) were first examined within two years after
      disease onset, and group 2 patients (n=50) at later time points. As primary
      measures sum scores were calculated for abnormalities of single and combined EP
      (visual (VEP), somatosensory (SEP), magnetic motor evoked potentials (MEP)). In
      patients examined early after disease onset (group 1), a significant predictive
      value for abnormal EP was found with MEP and SEP sum scores at first presentation
      correlating significantly with Expanded Disability Status Scale (EDSS) values
      after five years, while the VEP sum score was not. The cumulative number of
      abnormal MEP, SEP and VEP results also indicated higher degrees of disability
      (EDSS > or = 3.5) after five years. Combined pathological SEP and MEP findings at
      first presentation best predicted clinical disability (EDSS > or = 3.5) after
      five years (odds ratio 11.0). EP data and EDSS at first presentation were not
      significantly linked suggesting that EP abnormalities at least in part
      represented clinically silent lesions not mirrored by EDSS. For patients in later
      disease phases (group 2), no significant associations between EP data at first
      presentation and EDSS at five and ten years were detected. Together with clinical
      findings and MR imaging, combined EP data may help to identify patients at high
      risk of long-term clinical deterioration and guide decisions as to
      immunomodulatory treatment.

PMID- 16459721
TI  - No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in
      secondary progressive multiple sclerosis.
AB  - Intravenous immunoglobulins (IVIG) have been effective in reducing multiple
      sclerosis (MS) disease activity and improving disability scores. However, the
      mechanism by which this beneficial effect is achieved remains unclear. An effect
      of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role
      in the disease process - has been postulated in a number of animal and ex vivo
      studies. Hence, we performed a study on 34 patients with secondary progressive
      (SP) MS being treated with monthly IVIG or placebo for two years according to the
      protocol of the ESIMS study. Clinical outcome measures and cytokine production
      (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were
      recorded in all patients and compared with respect to the treatment group.
      Against our expectations, IVIG did not reduce the relapse rate or the progression
      of disability or cytokine production. Our data argue against an enduring
      immunomodulating effect of IVIG, at least in SPMS.

PMID- 16459722
TI  - Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for
      multiple sclerosis (INCOMIN Trial) II: analysis of MRI responses to treatment and
      correlation with Nab.
AB  - BACKGROUND: In RRMS, clinical exacerbations are usually associated with different
      types of active lesions at MRI, including: hyperintense lesions on T1-weighted
      post-gadolinium sequences; new hyperintense lesions or enlarging old lesions on
      PD/T2-weighted scans; or new hypointense lesions on T1-weighted pre-Gd sequences.
      OBJECTIVE/METHODS: Primary outcome was the occurrence of patients with at least
      one active MRI lesion of the different types indicated above during treatment
      with 250 microg every other day (EOD) interferon beta (IFNbeta)-1b or 30 microg
      once weekly (OW) IFNbeta-1a in outpatients with RRMS (INCOMIN Trial). RESULTS:
      The number of patients with at least one 'active' lesion, evaluated over the two
      year follow-up, was significantly (P = 0.014) lower in the EOD IFNbeta-1 b arm (1
      3/76, 17%) then in the OW IFNbeta-1a arm (25/73, 34%). NAb frequency over two
      year follow-up was 22/65 (33.8%) in the EOD IFNbeta-1b arm and 4/62 (6.5%) in the
      OW IFNbeta-1a arm, significantly greater in the EOD IFNbeta-1b arm. CONCLUSIONS:
      The development of MRI active lesions is strongly reduced by EOD-IFNbeta-1b
      compared with OW-IFNbeta-1a, indicating that EOD-IFNbeta-1b is more effective
      than OW-IFNbeta-1a in reducing ongoing inflammation and demyelination in MS.
      Logistic regression showed that NAb status did not affect the risk of MRI
      activity.

PMID- 16459724
TI  - An interdisciplinary approach to evaluating the need for assistive technology
      reduces equipment abandonment.
AB  - Assistive technology makes up a substantial portion of the direct cost of
      multiple sclerosis (MS). Equipment abandonment results in the needs of the
      disabled individual being unmet and places stress on the resources available for
      the funding of such equipment. The aim of the study was to demonstrate whether an
      interdisciplinary approach to evaluating and prescribing assistive technology
      reduces equipment abandonment in persons with MS. Data concerning assistive
      devices acquired by patients being followed at a rehabilitation centre in
      northern Italy from January 1997 to December 2002, were included in the study.
      Through December 1999, a physician in physical medicine and rehabilitation
      prescribed equipment based on a recommendation from the physical therapist. From
      2000 to 2002, patients were evaluated following a standardized protocol
      implemented by an interdisciplinary team comprised of a physical therapist,
      occupational therapist, physician in physical medicine and rehabilitation and
      psychologist. Assistive technology obtained during the study period was divided
      into two datasets based on the year that the aid was obtained: pre-intervention
      (January 1997 to December 1999) and intervention (January 2000 to December 2002).
      The analysis included a comparison of the two datasets on number and types of
      equipment abandoned, timing of abandonment and reasons why devices were
      abandoned. Fifty-four subjects obtained 151 assistive devices during the study
      period, 67 devices during pre-intervention and 84 with the intervention. The
      majority of devices were abandoned immediately or within the first year following
      obtainment in both groups. A comparison of the number of devices obtained during
      pre-intervention with those obtained during the intervention showed that the rate
      of equipment abandonment decreased significantly from 37.3 to 9.5%. An
      interdisciplinary approach to evaluating assistive technology needs does decrease
      the risk of equipment abandonment, although it does not completely solve the
      problem.

PMID- 16459723
TI  - Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis.
AB  - Cognitive dysfunction is considered one of the clinical markers of multiple
      sclerosis (MS). However, in the literature there are inconsistent reports on the
      prevalence of cognitive dysfunction, and separate data for the relapsing
      remitting (RR) type of the disease are not always presented. In this study, we
      submitted 461 RRMS patients to a battery of neuropsychological tests to
      investigate their impairment in various cognitive domains. As a consequence of
      the exclusion criteria, the sample is not fully representative of the entire
      population of RRMS patients. In this selected sample, when only the eight scores
      of a core battery (Mental Deterioration Battery) were considered (with respective
      cutoffs), it emerged that 31% of the patients were affected by some degree of
      cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had
      severe impairment. Information processing speed was the most frequently impaired
      area, followed by memory. When two other tests (SDMT and MCST) were added and
      cognitive domains were considered, it emerged that 39.3% of the patients were
      impaired in two or more domains. When four subgroups were obtained by means of
      cluster analysis and then compared, it emerged that information processing speed
      and memory deficits differentiated the still cognitively unimpaired from the
      mildly impaired MS patients. Significant associations were found between
      cognitive and clinical characteristics. However, due to the large sample size,
      clinically irrelevant relationships may also have emerged. Even with the
      limitations imposed by the sample selection and the possible underestimation of
      the prevalence and severity of cognitive dysfunction, these results seem to
      provide further evidence that information processing speed deficit may be an
      early and important marker of cognitive impairment in MS patients.

PMID- 16459725
TI  - Demographic and health-related factors associated with complementary and
      alternative medicine (CAM) use in multiple sclerosis.
AB  - Complementary and alternative medicine (CAM) use is high among people with
      multiple sclerosis (MS), yet there are no reports on the association between CAM
      use and health-related quality of life (HRQL) in MS. To examine this
      relationship, a cross-sectional survey and SF-12 was used to collect demographic
      and HRQL data from 1667 survey respondents. Factors examined for their
      association with CAM use included, age, gender, race, self-reported disease
      severity, disease-modifying drug (DMT) use, MS duration, MS type, education
      level, physical and mental well-being. Multiple regression analysis revealed that
      female gender, high education level, longer MS duration, lower physical well
      being and not using DMT were independent factors associated with both 'ever' and
      'current' CAM use. The finding that a drop in physical component score (PCS) of
      the SF-12 is independently associated with an increased odds of 'ever' CAM use,
      'current' CAM use, and 'past' CAM reflect an association of CAM use with PCS
      regardless of time of use. Although, temporality of this relationship cannot be
      established, as this was a cross-sectional study, a longitudinal study is
      warranted so that we can establish if HRQL is predictive for CAM use in MS.

PMID- 16459727
TI  - The effect of consent guidelines on a multiple sclerosis register.
AB  - BACKGROUND: The 1998 Data Protection Act and guidelines from the General Medical
      Council on informed consent have caused concern for medical researchers and
      particularly those involved in the management of disease registers. OBJECTIVE:
      The aim of this study was to determine rates of consent for a multiple sclerosis
      (MS) community-based register and to investigate authorization bias by examining
      the characteristics of those refusing consent. METHODS: A consent letter was
      developed with the advice and support of an advisory group which included people
      with MS. All people with MS on the prevalent register (n=820) were informed about
      the register and its purposes and asked to indicate whether they would like their
      details to be removed from the register. RESULTS: Thirty-four (4.1%) people with
      MS asked for their details to be removed from the register. There was a
      significant difference in disease course in this group with more patients with
      benign relapsing remitting disease compared to the prevalent population. There
      was no significant difference in age or sex distribution. The proportion of
      people not giving consent was similar to a local stroke register. Prospectively
      all new patients have given written informed consent. CONCLUSION: Patients
      refusing consent may have different disease characteristics than those who
      consent. The potential for response bias needs to be considered in the
      development of a UK MS register.

PMID- 16459726
TI  - Intrathecal baclofen for treatment of spasticity of multiple sclerosis patients.
AB  - We conducted a retrospective study of the case files of 64 multiple sclerosis
      (MS) patients presenting severe spasticity, who had received intrathecal (IT)
      baclofen test injections between 1992 and 2004 in a rehabilitation unit. In
      almost all cases of our series, IT baclofen was proposed to patients who were no
      longer able to walk. IT baclofen is a safe and effective treatment to reduce
      spasticity in MS patients. Despite an advanced stage of the disease at the time
      of pump placement, the complication rate was low and the efficacy of this
      treatment was maintained over time.

PMID- 16459728
TI  - Azathioprine myelosuppression in multiple sclerosis: characterizing thiopurine
      methyltransferase polymorphisms.
AB  - We describe two multiple sclerosis patients who developed pancytopenia following
      treatment with azathioprine. They were found to have the homozygous polymorphism
      for thiopurine methyltransferase deficiency and recovered after cessation of drug
      therapy. We review the literature concerning this molecular derangement and
      underscore the importance of performing surveillance testing for allelic
      characterization prior to treatment intervention with this agent for immune
      mediated disorders.

PMID- 16459729
TI  - Core hypothermia in multiple sclerosis: case report with magnetic resonance
      imaging localization of a thalamic lesion.
AB  - Hypothermia is a rare condition in multiple sclerosis (MS). We report on a
      patient with a long-standing secondary progressive MS and six episodes of
      recurring hypothermia down to 29.9 degrees C with associated hypotension,
      bradycardia, coagulopathy and electrolyte dysequilibrium. Magnetic resonance
      imaging (MRI) demonstrated severe involvement of the corpus callosum with an
      associated lesion in the right posterior thalamus. These findings may link
      hypothermia in MS with callosal and associated thalamic pathology to Shapiro's
      syndrome, where agenesis of the corpus callosum and associated abnormalities are
      related to episodic spontaneous hypothermia. In MS, hypothermic episodes may be
      triggered by preceding infections, as shown in the present case.

PMID- 16459730
TI  - Crossed aphasia in multiple sclerosis.
AB  - Aphasia is a rare sign of multiple sclerosis (MS). Several different forms of
      aphasia have been reported in MS. We report, to our knowledge, the first case of
      a MS patient with crossed aphasia during an attack.

PMID- 16459731
TI  - Misuse of serum matrix metalloproteinase (MMP)-9 and tissue inhibitor of
      metalloproteinase (TIMP)-1 as a biomarker in multiple sclerosis.

PMID- 16459732
TI  - [CME ultrasonography. 9. Nervousness, weight loss].

PMID- 16459733
TI  - [What is your diagnosis? Solution on the next page].

PMID- 16459734
TI  - [Check-up: general aspects].
AB  - A Check-up is characterized as a medical examination and a counselling of
      asymptomatic persons. The aim of such a Check-up is the identification of
      modifiable risk factors for different illnesses and/or the detection of a
      treatable, latent disease. The value and the cost-effectiveness of regular Check
      up examinations can be assessed in scientific enquiries. However, the question
      whether regular Check-up examinations are or are not of value from an individual
      or societal point of view cannot be answered by the results of evaluative studies
      alone. This question should be discussed between an individual person and a
      physician or, in general, on a societal level. In addition, in this paper we
      discuss various tests recommended for a patient who requires a Check-up
      examination.

PMID- 16459735
TI  - [Respiratory syncytial virus infections: measures in immunocompromised patients].
AB  - RSV infections are an annually recurring problem of significant morbiditiy and
      mortality in the immunocompromised host, especially after lung and stem cell
      transplantation. The effectiveness of hygienic (isolation) and therapeutic
      (ribavirin, immunoglobulin, pavilizumab) measures depends of high index of
      suspicion and rapid diagnostic confirmation by the antigen test, PCR and/or
      culture. Allocation of resources require stratification of measures according to
      the known or estimated risk for complications.

PMID- 16459736
TI  - [Treatment of osteoporosis--the new role of the orthopaedic surgeon].
AB  - Fractures which are caused by falling from standing height or less are named
      "fragility fractures". These fractures may indicate neglected osteoporosis and
      will occur even more frequently in the future, due to the demographic change.
      This is why osteoporosis will become a challenge to our healthcare systems. For
      the orthopaedic surgeon treatment of osteoporosis was limited to fracture
      fixation in the past. As this approach is very focussed towards the fracture as
      the major complication of osteoporosis, there is a big potential for improvement.
      It is important to know that such patients suffering from a first fragility
      fracture are at high risk for being hit by a second or further fragility
      fractures. A fracture prevention programme should therefore become a mandatory
      requirement for these patients in the future. The orthopaedic surgeons will be
      the key players who should put this approach into effect. As we treat most
      patients with fragility fractures it is our privilege to identify those patients
      who will most likely benefit from fracture prevention.

PMID- 16459737
TI  - [Eosinophilia, diarrhea and asthma in a young woman].
AB  - We present the case of a young woman that was diagnosed with Churg-Strauss
      syndrome. The classical as well as the atypical symptoms, signs and findings are
      discussed in the context of clinically relevant differential diagnoses. The
      diagnostic criteria and the relevant aspects of pathogenesis, clinical course and
      treatment are reviewed. In addition, the similarities and differences with
      respect to the other idiopathic interstitial eosinophilic pneumopathies are
      described.

PMID- 16459739
TI  - ["Some take to drink, some take up arms. I prefer study of medicine"].

PMID- 16459738
TI  - [Proteinuria in the nephrotic range].

PMID- 16459740
TI  - Flying monkeys. Dealing with "down" time.

PMID- 16459741
TI  - From helper to hostage. A paramedic student is caught in the crossfire.

PMID- 16459742
TI  - The ABCs of scene size-up.

PMID- 16459743
TI  - Teaching affective concepts in the EMS classroom. Affective is more than
      feelings.

PMID- 16459744
TI  - Driving online. Internet-based program for emergency vehicle safe operations now
      available.

PMID- 16459745
TI  - Broken windows. Preventing system decay.

PMID- 16459746
TI  - Stepchild O'mine. How the fire service can do right by EMS.

PMID- 16459747
TI  - A fire department ridealong. What I knew and what I learned.

PMID- 16459748
TI  - No hospital left behind. How a heartland healthcare system powered up for
      potential disaster.

PMID- 16459749
TI  - Money matters.

PMID- 16459750
TI  - Prehospital rapid sequence intubation.

PMID- 16459751
TI  - Assessing endotracheal tube cuff pressure.

PMID- 16459752
TI  - Beyond the basics: Airway assessment.

PMID- 16459753
TI  - The evidence that supports the effectiveness of certain psychopharmacologic
      agents and concern over the appropriate use of others.

PMID- 16459754
TI  - How solid is the evidence for the efficacy of mood stabilizers in bipolar
      disorder?
AB  - This article addresses the question of what defines a "mood stabilizer." Dr.
      Bauer expands upon his comprehensive 2004 review by (a) summarizing the
      conceptual and methodological approach to evaluating the evidence for
      pharmacotherapeutic options for bipolar disorder; (b) updating the evidence base
      from recently published controlled monotherapy trials; and (c) review the
      evidence base for combination therapy options. Finally, he identifies the
      shortcomings and sources of potential bias in our evidence base, which is
      critical for an accurate reading of the literature now and in the future.

PMID- 16459755
TI  - Pharmacologic management of borderline personality disorder: a case study.
AB  - General principles of the "outcome-focused" model of psychopharmacologic
      management of patients with BPD are illustrated using the case of Ms. A, a
      patient with borderline personality disorder (BPD) experiencing impulsivity such
      as suicidal behavior, chronic insomnia and concurrent substance abuse. The model
      includes (1) measurement of specific behavioral outcomes related to functioning;
      (2) assessment of the role of substance use/abuse in patients with BPD; (3)
      consideration of interventions to clarify and strengthen the boundaries of the
      therapeutic relationship-including short lengths of time between prescription
      refills, medication contracts outlining consequences if substances are obtained
      outside of the relationship, and urine testing to ascertain compliance; (4) an
      understanding of the psychodynamic meanings attributed to medication while
      positive and negative medication effects are monitored with treatment response or
      transference issues, and; (5) use of the N-of-1 approach to test the new
      medication vs previous medications using patient specific outcomes that are
      anticipated to change with the pharmacologic management.

PMID- 16459756
TI  - Inappropriate medication use in the elderly.
AB  - Medications are commonly used in the elderly population. Because of a variety of
      treatments now available, many disease states now have very effective treatment.
      As a result, our elderly patients often take multiple medications. Due to various
      changes that occur, the elderly are at increased risk of adverse drug effects and
      drug toxicity potentially resulting in serious complications. Some medications
      have a greater potential to cause harm and these should be made aware to those
      who prescribe to elderly patients. Some of these medications should not be used
      if at all possible, while others, if used, need to be used with great caution,
      watching carefully for signs of problems. This article describes a variety of
      medications which have an increased potential for causing harm in elderly
      patients and gives alternatives of safer medications consideration.

PMID- 16459757
TI  - Metabolic and endocrine effects of sleep deprivation.
AB  - Sleep deprivation has multiple effects on endocrine and metabolic function. In
      particular, sleep restriction is accompanied by increased cortisol levels in the
      afternoon and early evening and a shorter quiescent period compared with extended
      sleep periods. Those alterations could facilitate central and peripheral
      disturbances that are associated with glucocorticoid excess, such as memory
      deficits, and are similar to those observed in aging. Thus, chronic sleep loss
      could contribute to acceleration of the aging process. Sleep restriction is also
      associated with an impairment of carbohydrate tolerance, similar to that observed
      in individuals with clinically significant impaired glucose tolerance. Thus,
      chronic sleep deprivation may increase the risk for diabetes. Finally, sleep
      plays an important role in energy balance. Partial sleep deprivation was found to
      be associated with a decrease in plasma levels of leptin and a concomitant
      increase in plasma levels of ghrelin; subjective ratings of hunger and appetite
      also increased (the appetite for protein-rich foods was not significantly
      affected). Moreover, a remarkable correlation was found between the increase in
      hunger and the increase in the ghrelin:leptin ratio. Thus, the neuroendocrine
      regulation of appetite and food intake appears to be influenced by sleep
      duration, and sleep restriction may favor the development of obesity.

PMID- 16459758
TI  - Reliability and risks of generic psychopharmacologic agents.

PMID- 16459759
TI  - Shortfalls begin to bite.

PMID- 16459760
TI  - Counting the cost.

PMID- 16459761
TI  - From the top.
AB  - The Alexander technique can help nurses deal with their stressful jobs, as one
      group recently discovered in a session aimed at their specific needs. While work
      pressure helps people maintain motivation, excessive amounts can be stressful and
      damaging. The Alexander technique involves learning about stress-induced bad
      habits, such as tightening the neck muscles. It also involves mental techniques
      and discipline. Easing the weight-bearing points on the feet can be restorative
      after a busy day.

PMID- 16459762
TI  - Taking a gamble.
AB  - A new law intended to make access to gambling easier could put more people at
      risk of gambling addiction. Currently there is little mental healthcare provision
      for people who get into difficulties. Gambling is being promoted as a leisure
      activity. Casinos can now sign up members without the need for a 24-hour cooling
      off period. People addicted to gambling experience physical symptoms if they fail
      to get their 'fix'. Some gambling addicts have dual addictions as they are also
      addicted to drugs or alcohol.

PMID- 16459763
TI  - Keeping it in the family.

PMID- 16459764
TI  - Rehabilitation services for patients undergoing peritoneal dialysis in Hong Kong.
AB  - AIM: To examine whether rehabilitation services are provided to patients
      undergoing peritoneal dialysis in Hong Kong, and the impact of such services on
      patients' lives. METHOD: Semi-structured interviews were conducted with 30
      participants. Transcripts were analysed using thematic content analysis.
      Categories and codes were identified from the first 21 interviews, but
      questioning continued throughout the process to saturate the categories.
      FINDINGS: Rehabilitation is not provided to patients undergoing peritoneal
      dialysis in Hong Kong. Most support services are initiated by patients
      themselves. CONCLUSION: To enable these patients to lead productive lives,
      efforts should be made to provide them with the required medical information to
      help them make choices. Nurses should provide appropriate training to peer
      counsellors and regular exercise should be encouraged to allow patients to
      maintain physical health and mobility. Support for retraining and employment is
      also important. Counselling on finding a purpose through other roles is
      beneficial for those who cannot return to work.

PMID- 16459765
TI  - The role of community matrons in supporting patients with long-term conditions.
AB  - The new emphasis on patients with long-term conditions offers a vision of a
      primary health care service that will reduce the need for hospital admission.
      This article debates the implications of introducing the new advanced nursing
      role of community matron for patients with long-term conditions and the
      opportunities this may offer nursing.

PMID- 16459766
TI  - Clinical governance: applying theory to practice.
AB  - Although clinical governance is prominent in modern health care, it is often
      perceived as an abstract concept. This article explains the key components of
      clinical governance and relates these to nursing practice. The author emphasises
      that clinical governance should be viewed as an opportunity to improve care
      delivery.

PMID- 16459767
TI  - Pain in older people.

PMID- 16459768
TI  - Sleeping sickness.

PMID- 16459769
TI  - To help is human.

PMID- 16459770
TI  - Survival techniques.

PMID- 16459771
TI  - Anaerobic digestion: a new model for plant-wide wastewater treatment process
      modelling.
AB  - This paper describes a new anaerobic digestion model for wastewater treatment
      systems (MantisAD). The model has been developed specifically for plant-wide
      wastewater treatment modelling. That is, rather than modelling nitrogen as a
      series of fractions of other carbonaceous state variables, this new model
      includes six dedicated nitrogen state variables. This structure makes this new
      anaerobic model easier to incorporate into plant-wide models by simplifying the
      aerobic/anaerobic model interfaces. The model is complete and initial success
      with the model has been achieved. A comprehensive description of the model
      including a Petersen Matrix representation of the model is included as is a case
      study in which the model is applied to full-scale anaerobic digesters.

PMID- 16459772
TI  - Prediction of sulfide formation in sewer pressure mains based on the IWA
      Anaerobic Digestion Model No. 1 (ADM1).
AB  - In this paper a new approach is presented to predict sulfide formation in sewers
      based on the IWA Anaerobic Digestion Model No. 1 (ADM1). Compared with existing
      models the ADM1 has two crucial advantages. Firstly, it simulates anaerobic
      digestion processes, of which sulfide formation is the final step. Secondly, it
      uses a more detailed description of the waste water composition. In order to
      obtain reliable data for calculation an experimental set-up for measuring the
      Oxygen Uptake Rate (OUR) is used. An implementation of sulfide formation
      processes into the model matrix is proposed.

PMID- 16459773
TI  - Performance comparison of a continuous-flow stirred-tank reactor and an anaerobic
      sequencing batch reactor for fermentative hydrogen production depending on
      substrate concentration.
AB  - This study was conducted to compare the performance of a continuous-flow stirred
      tank reactor (CSTR) and an anaerobic sequencing batch reactor (ASBR) for
      fermentative hydrogen production at various substrate concentrations. Heat
      treated anaerobic sludge was utilized as an inoculum, and hydraulic retention
      time (HRT) for each reactor was maintained at 12 h. At the influent sucrose
      concentration of 5 g COD/L, start-up was not successful in both reactors. The
      CSTR, which was started-up at 10 g COD/L, showed stable hydrogen production at
      the influent sucrose concentrations of 10-60 g COD/L during 203 days. Hydrogen
      production was dependent on substrate concentration, resulting in the highest
      performance at 30 g COD/L. At the lower substrate concentration, the hydrogen
      yield (based on hexose consumed) decreased with biomass reduction and changes in
      fermentation products. At the higher substrate concentration, substrate
      inhibition on biomass growth caused the decrease of carbohydrate degradation and
      hydrogen yield (based on hexose added). The ASBR showed higher biomass
      concentration and carbohydrate degradation efficiency than the CSTR, but hydrogen
      production in the ASBR was less effective than that in the CSTR at all the
      substrate concentrations.

PMID- 16459774
TI  - Anaerobic bio-hydrogen production using pre-heated river sediments as seed
      sludge.
AB  - Anaerobic bio-hydrogen production is the focus in the field of bio-energy
      resources. In this paper, a series of batch experiments were conducted to
      investigate the effects of several factors on anaerobic bio-hydrogen producing
      process carried out by pre-heated river sediments. The results showed that
      several factors such as substrate and its concentration, temperature and the
      initial pH value could affect the anaerobic bio-hydrogen production in different
      levels. At 35 degrees C and the initial pH of 6.5, using glucose of 20,000 mg
      COD/L as substrate, the highest hydrogen production of 323.8 ml-H2/g TVS in a 100
      ml batch reactor was reached, the specific hydrogen production rate was 37.7 ml
      H2/g TVS h, and the hydrogen content was 51.2%. Thereafter using the same pre
      heated river sediments as seed sludge, continuous anaerobic bio-hydrogen
      production was achieved successfully in a lab-scale CSTR with gas-separator. At
      the organic loading rate of 36 kg COD/m3 d, the highest hydrogen production was
      6.3-6.7 l-H2/l-reactor d, the specific hydrogen production was 1.3-1.4 mol-H2/mol
      glucose, and the hydrogen content in the gas was 52.3%. The effluent of the bio
      reactor contained some small molecular organics, mainly including ethanol,
      acetate, butyrate and their molar proportion is 1:1:0.6.

PMID- 16459775
TI  - Anaerobic treatment of Hong Kong leachate followed by chemical oxidation.
AB  - Landfill leachate of Hong Kong was first treated by the upflow anaerobic sludge
      blanket (UASB) process. At 37 degrees C, pH 7.1-8.5 and a HRT of 5.1-6.6 days,
      the process removed 66-90% of COD in the leachate for loading rates of 1-2.4 g
      COD/l day depending on the strength of landfill leachate. The final effluent
      contained 1440-1910 mg-COD/l and 70-91 mg-BOD/l. About 92.5% of the total COD
      removed was converted to methane and the rest was converted to biomass with an
      average net growth yield of 0.053 g-VSS/g-COD-removed. The granules developed in
      the UASB reactor were 0.5-1.5 mm in size and exhibited good settleability. The
      UASB effluent was then further polished by two oxidation processes. The UASB
      ozonation process removed 93.0% of the 12900 mg/l of COD from the raw leachate.
      The UASB-Fenton-ozonation process improved the COD removal efficiency to 99.3%.
      The final effluent had only 85 mg/l of COD and 10 mg/l of BOD5. Ozonation was
      most effectively conducted at pH 7-8 with the addition of 300 mg/l of H2O2 and
      for the duration of 30 min. Ozonation also significantly improved the
      biodegradability of the organic residues. Nearly 50% of these residues could be
      used as carbon source in denitrification.

PMID- 16459776
TI  - Effect of enzymatic pretreatment on solubilization and volatile fatty acid
      production in fermentation of food waste.
AB  - Food waste can be a valuable carbon source in biological nutrient removal (BNR)
      systems because of the high C/N and C/P ratio. However, pretreatment is necessary
      to promote hydrolysis of food waste because of the high concentration of volatile
      solids associated with organic matter. The influence of the enzymatic
      pretreatment on acid fermentation of food waste was investigated in this study.
      Solubilization of particulate matter in food waste was carried out using
      commercial enzymes. The acidification efficiency and the volatile fatty acid
      (VFA) production potential of enzymatically pretreated food waste were examined.
      The highest volatile suspended solid (VSS) reduction was obtained with an enzyme
      mixture ratio of 1:2:1 for carbohydrase: protease: lipase. An optimum enzyme
      dosage for solubilization of food waste was 0.1% (V/V) with the enzyme mixture
      ratio of 1:2:1. In the acid fermentation of enzymatically pretreated food waste,
      the maximum VFA production and the highest VFA fraction in soluble COD (SCOD)
      were also achieved at 0.1% (V/N) of total enzyme dosage. Increase in VFA
      production at this level of enzyme dosage was over 300% compared with the control
      fermenter. The major form of VFA produced by fermentation was n-butyrate followed
      by acetate.

PMID- 16459777
TI  - Evaluation of wastewater characterization methods.
AB  - Wastewater contains various organic components with different physical and
      biochemical characteristics. ASM No. 1 distinguishes two categories of
      biodegradable organic matter in wastewater, rapidly and slowly biodegradable. In
      general there are two methods for wastewater characterization: based on
      filtration in combination with a long-term BOD test or based on a respirogram. By
      comparing both approaches, we showed that in wastewater three categories of
      organic compounds with different biodegradation rates can be distinguished. These
      categories are referred to as readily biodegradable, rapidly hydrolysable and
      slowly hydrolysable organic matter. The total biodegradable COD can be found from
      a long-term BOD-test combined with a curve-fit and the readily biodegradable and
      rapidly hydrolysable from a respirogram. The slowly hydrolysable is the
      difference between total biodegradable COD and the sum of readily biodegradable
      and rapidly hydrolysable COD. Simulation with characterization based on
      filtration for a pre-anoxic reactor with a certain N-removal compared with the N
      removal of the same plant with wastewater according to the modified
      characterization shows different results of each wastewater, especially with
      regard to the effluent nitrate concentration.

PMID- 16459778
TI  - Limitations of ASM1 and ASM3: a comparison based on batch oxygen uptake rate
      profiles from different full-scale wastewater treatment plants.
AB  - The two most popular models for the description of the biological COD removal are
      ASM1 and ASM3. However, some numerical inconsistencies arise when using these
      models to interpret the data obtained in short-term respirometric batch
      experiments. In this study, both models are fitted to four different
      respirometric batch profiles obtained with biomass from different WWTP. The
      parameter estimation results and the practical (local) identifiability are
      analysed, and the limitations of both models are discussed. The growth yield
      obtained by fitting ASM1 to the short-term respirometric batch profiles is higher
      than the default one, as well as the storage yield obtained by fitting ASM3 is
      lower than the default one. Based on these values, possible improvements to the
      modelling of the biological COD removal, such as the inclusion of simultaneous
      growth and storage on external substrate, are proposed.

PMID- 16459779
TI  - Short circuiting in a denitrifying activated sludge tank.
AB  - The presence of a short circuit flow in a denitrifying activated sludge tank was
      identified and modelled. Tracer tests with pulse addition of lithium salt were
      used to investigate the hydraulics of the tank. The lithium concentration in the
      effluent was detected and residence time distribution (RTD) curves were
      generated. Hydraulic models based on completely stirred tank reactors (CSTRs) in
      series were generated from the RTD curves and the models were compared. The short
      circuit problem was successfully described using the Martin model, where the
      inflow is divided into two strands. Each strand was modelled as a number of CSTRs
      in series. At a normal flow the results of the model show that the tank has 12.8%
      dead volume, 85.8% main volume and 1.3% short circuiting volume. The inflow was
      divided into 91.9% entering the main volume and 8.1% entering the short
      circuiting volume. The mean velocity of the short circuiting stream was estimated
      to 0.4 m/s. At maximum flow the short circuiting stream was even larger and
      handled 24.3% of the flow. The short circuiting stream was identified in the
      upper part of the tank due to the position of the inlet and the outlet. The
      configuration of a tank including the use of baffles, the geometry of the inlet
      and mixer configuration should be considered carefully if short circuiting is to
      be avoided.

PMID- 16459780
TI  - Biological treatability of raw and ozonated synthetic penicillin formulation
      effluent.
AB  - Chemical pre-treatment of synthetic Procaine Penicillin G (PPG) effluent with
      ozone (applied dose = 1440 mg/h; treatment duration = 60 min) at pH = 7 was
      investigated. Successive biological treatability studies were performed with raw,
      ozonated penicillin formulation effluent and synthetic readily biodegradable
      substrate as simulated domestic wastewater. The PPG effluent additions were
      adjusted to constitute approximately 30% of the total COD in the reactor.
      Ozonation of PPG effluent resulted in practically complete removal of the parent
      pollutant accompanied by 40% COD abatement. Speaking for the raw PPG effluent,
      prolonged acclimation periods were necessary to obtain significant COD removal
      efficiencies. Batch activated sludge treatment experiments and respirometric
      studies have demonstrated that the selection of true retention time is extremely
      crucial for having high amount of slowly hydrolysable substrate or complex
      wastewater, like pharmaceutical effluent. The effect of ozonation time on
      biological treatability performance of PPG has been evaluated in the study. Pre
      ozonation of PPG effluent did not improve its ultimate biodegradability.

PMID- 16459781
TI  - Biodegradation of phenol at low temperature using two-phase partitioning
      bioreactors.
AB  - Two-phase partitioning bioreactors offer many advantages for the removal of toxic
      pollutants. In particular, such systems can be loaded with very large quantities
      of pollutants without risks of microbial inhibition, they are self-regulated and
      they prevent the risks of hazardous pollutant volatilisation during aerobic
      treatment. However, their potential has never been tested at low temperatures.
      Phenol biodegradation by a cold adapted Pseudomonas strain was therefore tested
      at 14 or 4 degrees C using 2-undecanone, diethyl sebacate or 2-decanone as
      organic phases in a two-phase partitioning bioreactor. The three solvents were
      biocompatible at 14 degrees C but evidence was found that diethyl sebacate was
      biodegraded by the bacteria and this solvent was not tested further. Although
      only 2-decanone was suitable at 4 degrees C, phenol biodegradation was more
      efficient in 2-undecanone at 14 degrees C, reaching a maximum volumetric rate
      (based on the volume of aqueous phase) of approximately 1.94 g/L.day after 47 h
      of cultivation. In 2-decanone at 14 degrees C, evidence was found that phenol
      degradation was limited by the release of biosurfactants, which increased the
      solubility and toxicity of the solvent in the aqueous phase inhibiting microbial
      activity. This study therefore shows that pollutant removal at low temperature is
      feasible but that the production of biosurfactants can have a negative impact on
      the process and must be taken into consideration when selecting the organic
      solvent. Future work should therefore focus on the selection of solvents suitable
      for use at temperatures below 14 degrees C.

PMID- 16459782
TI  - Performance evaluation of physicochemical processes for biologically pre-treated
      livestock wastewater.
AB  - The use of a combination of biological and physicochemical methods is a promising
      technique to reduce highly concentrated pollutants in livestock wastewater:
      firstly, biodegradable organic matters, nitrogen and a part of phosphorus should
      be removed in a biological treatment process and then residual non-biodegradable
      organic matters, color and phosphorus be eliminated by physicochemical methods.
      In this study, therefore, the integrations of chemical coagulation, activated
      carbon adsorption, Fenton oxidation and ozonation were evaluated to provide an
      appropriate post-treatment process for biologically pre-treated livestock
      wastewater. With applying a single method such as coagulation and Fenton
      oxidation, a yellowish brown color and COD still remained. According to the
      experimental result, the quality of treated wastewater including color was enough
      to be discharged after chemical coagulation followed by ozonation or Fenton
      oxidation process. Among these, ozonation was the most effective technology for
      decolorization. Neither simple biological nor physicochemical process provides an
      adequate treatability for the sufficient depletion of organics and decolorization
      when treating livestock wastewater. Considering only the removal efficiency, the
      integration of Fenton oxidation and ozonation would be an efficient alternative
      as a post-treatment.

PMID- 16459783
TI  - High-rate wastewater treatment combining a moving bed biofilm reactor and
      enhanced particle separation.
AB  - Many cities around the world are looking for compact wastewater treatment
      alternatives since space for treatment plants is becoming scarce. In this paper
      development of a new compact, high-rate treatment concept with results from
      experiments in lab-scale and pilot-scale are presented. The idea behind the
      treatment concept is that coagulation/floc separation may be used to separate
      suspended and colloidal matter (resulting in > 70% organic matter removal in
      normal wastewater) while a high-rate biofilm process (based on Moving Bed biofilm
      reactors) may be used for removing low molecular weight, easily biodegradable,
      soluble organic matter. By using flotation for floc/biomass separation, the total
      residence time for a plant according to this concept will normally be < 1 hour. A
      cationic polymer combined with iron is used as coagulant at low dosages (i.e. 1-2
      mg polymer/l, 5-10 mg Fe/l) resulting in low sludge production (compared to
      conventional chemical treatment) and sufficient P-removal.

PMID- 16459784
TI  - Pilot-scale studies on biological treatment of hypersaline wastewater at low
      temperature.
AB  - In order to investigate the feasibility of biological treatment of hypersaline
      wastewater produced from toilet flushing with seawater at low temperature, pilot
      scale studies were established with plug-flow activated sludge process at low
      temperature (5-9 degrees C) based on bench-scale experiments. The critical
      salinity concentration of 30 g/L, which resulted from the cooperation results of
      the non-halophilic bacteria and the halophilic bacteria, was drawn in bench-scale
      experiments. Pilot-scale studies showed that high COD removal efficiency, higher
      than 80%, was obtained at low temperature when 30 percent seawater was
      introduced. The salinity improved the settleability of activated sludge, and
      average sludge value dropped down from 38% to 22.5% after adding seawater.
      Seawater salinity had a strong negative effect on notronomonas and nitrobacter
      growth, but much more on the nitrobacter. The nitrification action was mainly
      accomplished by nitrosomonas. Bench-scale experiments using two SBRs were carried
      out for further investigation under different conditions of salinities, ammonia
      loadings and temperatures. Biological nitrogen removal via nitrite pathway from
      wastewater containing 30 percent seawater was achieved, but the ammonia removal
      efficiency was strongly related not only to the influent ammonia loading at
      different salinities but also to temperature. When the ratio of seawater to
      wastewater was 30 percent, and the ammonia loading was below the critical value
      of 0.15 kgNH4+-N/(kgMLSS.d), the ammonia removal efficiency via nitrite pathway
      was above 90%. The critical level of ammonia loading was 0.15, 0.08 and 0.03
      kgNH4+-N/(kgMLSS.d) respectively at the different temperature 30 degrees C, 25
      degrees C and 20 degrees C when the influent ammonia concentration was 60-80 mg/L
      and pH was 7.5-8.0.

PMID- 16459785
TI  - Improving chlorine disinfection of wastewater by ultrasound application .
AB  - The presence of soluble organic material as well as high concentrations of
      suspended matter in waters and wastewaters affect the efficiency when chlorine is
      used as disinfection agent. The objective of our work is to explore to which
      extend ultrasonic treatment can facilitate wastewater disinfection with chlorine
      in order to bring down doses of ecologically questionable chlorine and to shorten
      contact times. Sewage treatment plant (STP) effluents with different
      concentrations of suspended solids are exposed to sonication in combination with
      chlorine dosage. We observed that enhancement of chlorine efficiency is better
      for samples with higher concentrations of suspended matter. For samples with a
      TSS concentration of 50 mg/L chlorination efficiency (2 mg/L) can be doubled from
      0.7 to 1.4 log when treated simultaneously with 20 kHz ultrasound for 5 minutes,
      i.e. levels of indicator organisms can be brought down to numbers that
      conventionally require far higher doses of chemical disinfectants. As subsequent
      sonication/chlorination does not have the same significant effect as simultaneous
      application of these two means, ultrasound does not just have a declumping
      effect; it seems that ultrasound application provokes a better chlorine
      dispersion in the aqueous media which improves the fast chemical and bactericidal
      reaction.

PMID- 16459786
TI  - Determination of fragrances at ng/L levels using CLSA and GC/MS detection.
AB  - Polycyclic and nitro musks and two fragrances (Acetyl cedrene and Amberonne) have
      been determined and quantified in influent and effluent waste water, river water
      and tap water samples from different European countries by closed loop stripping
      analysis (CLSA) as a method of preconcentration and GC/MS operating in the SIM
      mode. Limits of detection; precision expressed as repeatability and
      reproducibility relative standard deviations of the method; matrix effects and
      the estimation of the uncertainty have been evaluated. All samples contained
      different musks at ng/l levels being the polycyclic musks Galaxolide and Tonalide
      and both fragrances, Amberonne and Acetyl cedrene the most abundant. Removal of
      these main compounds is achieved partially in all waste water treatment plants
      studied. These results suggest the importance of studying and controlling the
      presence of these ubiquitous environmental compounds in water systems.

PMID- 16459787
TI  - The influence of heavy metals on the production of extracellular polymer
      substances in the processes of heavy metal ions elimination.
AB  - Wastewaters from a chemical industry polluted by heavy metal ions represent a
      hazard for all living organisms. It can mean danger for ecosystems and human
      health. New methods are sought alternative to traditional chemical and physical
      processes. Active elimination process of heavy metals ions provided by living
      cells, their components and extracellular products represents a potential way of
      separating toxic heavy metals from industrial wastewaters. While the abilities of
      bacteria to remove metal ions in solution are extensively used, fungi have been
      recognized as a promising kind of low-cost adsorbents for removal of heavy-metal
      ions from aqueous waste sources. Yeasts and fungi differ from each other in their
      constitution and in their abilities to produce variety of extracellular polymeric
      substances (EPS) with different mechanisms of metal interactions. The
      accumulation of Cd(2+), Cr(6+), Pb(2+), Ni(2+) and Zn(2+) by yeasts and their EPS
      was screened at twelve different yeast species in microcultivation system
      Bioscreen C and in the shaking Erlenmayer's flasks. This results were compared
      with the production of yeast EPS and the composition of yeast cell walls. The EPS
      production was measured during the yeast growth and cell wall composition was
      studied during the cultivations in the shaking flasks. At the end of the process
      extracellular polymers and their chemical composition were isolated and amount of
      bound heavy metals was characterized. The variable composition and the amount of
      the EPS were found at various yeast strains. It was influenced by various
      compositions of growth medium and also by various concentrations of heavy metals.
      It is evident, that the amount of bound heavy metals was different. The work
      reviews the possibilities of usage of various yeast EPS and components of cell
      walls in the elimination processes of heavy metal ions. Further the structure and
      properties of yeasts cell wall and EPS were discussed. The finding of mechanisms
      mentioned above is necessary to identify the functional groups entered in the
      metals elimination processes.

PMID- 16459788
TI  - Effects of surfactants originating from reuse of greywater on capillary rise in
      the soil.
AB  - Greywater is all domestic wastewater excluding toilet effluents. Detergents
      contain surfactants, which account for the highest concentration of organic
      chemicals in average domestic wastewater. Accumulation of surfactants in
      greywater-irrigated soils was determined in three household gardens. The effect
      of surfactants on capillary rise in loess and sand was then tested in the range
      of concentrations found in the garden soils. The capillary rise of freshwater in
      sieved oven-dried soil mixed with different concentrations of laundry detergent
      solution (10% w/w moisture content) was determined. In a second setup, the soil
      was mixed with freshwater and the rising solution contained different
      concentrations of detergent solution. The introduction of laundry solution to the
      soils caused a significant decrease in the capillary rise over the range of
      concentrations that is found in greywater-irrigated soils. The effect was more
      noticeable in the sand than in the loess. Interestingly, in the second setup, the
      capillary rise of the laundry solutions in the sand was almost similar to that of
      freshwater, whereas in the loess the capillary rise was significantly reduced. It
      is suggested that accumulation of surfactants in the soil might form water
      repellent soils that have a significant effect on agricultural productivity and
      environmental sustainability.

PMID- 16459789
TI  - Emission of greenhouse gases from constructed wetlands for wastewater treatment
      and from riparian buffer zones.
AB  - We measured N2O, CH4 and CO2 fluxes in horizontal and vertical flow constructed
      wetlands (CW) and in a riparian alder stand in southern Estonia using the closed
      chamber method in the period from October 2001 to November 2003. The average
      rates of N20, CH4 and CO2 emission from the riparian gray alder stand were from 
      0.4 to 58 microg N2O-N m(-2) h(-1) and 0.1-265 microg CH4-C m(-2) h(-1), 55-61 mg
      CO2-C m(-2) h(-1), respectively. The average N2O-N emission from the microsites
      above the inflow pipes of horizontal subsurface flow (HSSF) CWs was 6.4-31 microg
      N2O-N m(-2) h(-1), whereas the outflow microsites emitted 2.4-8 microg N2O-N m(
      2) h(-1). In vertical subsurface flow (VSSF) beds the same value was 35.6-44.7
      microg N2O-N m(-2) h(-1). The average CH4 emission from the inflow and outflow
      microsites in the HSSF CWs differed significantly ranging from 640 to 9715 and
      from 30 to 770 microg CH4-C m(-2) h(-1), respectively. The average CO2 emission
      was somewhat higher in VSSF beds (140-291 mg CO2-C m(-2) h(-1)) and at inflow
      microsites of HSSF beds (61-140 mg CO2-C m(-2) h(-1)). The global warming
      potential (GWP) from N2O and CH4 was comparatively high in both types of CWs (4.8
      +/- 9.8 and 6.8 +/- 16.2 t CO2 eq ha(-1) a(-1) in the HSSF CW 6.5 +/- 13.0 and
      5.3 +/- 24.7 t CO2 eq ha(-1) a(-1) in the hybrid CW, respectively). The GWP of
      riparian alder forest from both N2O and CH4 was relatively low (0.4 +/- 1.0 and
      0.1 +/- 0.30 t CO2 eq ha(-1) a(-1), respectively), whereas the CO2-C flux was
      remarkable (3.5 +/- 3.7 t ha(-1) a(-1). The global influence of CWs is not
      significant. Even if all the global domestic wastewater were treated by wetlands,
      their share in the trace gas emission budget would be less than 1%.

PMID- 16459790
TI  - Incorporation of hydrophobized mineral particles in activated sludge flocs: a way
      to assess ballasting efficiency.
AB  - The role of mineral surface hydrophobicity in attachment to activated sludge
      flocs was investigated. Fluorite and quartz particles of similar granulometry
      were hydrophobized by adsorbing sodium oleate and dodecylamine chloride,
      respectively. Mineral hydrophobicity was assessed by flotation expriments. The
      attachment of particles to microbial flocs was determined by optical microscopy.
      The results indicate that hydrophobized particles are always better incorporated
      within activated sludge flocs than non-coated particles. A comparison with
      Aquatal particles used as sludge ballast reveals that hydrophobized minerals are
      associated with microbial flocs to the same extent.

PMID- 16459792
TI  - Activated sludge image analysis system: monitoring settleability and effluent
      clarity.
AB  - A fully automized image analysis procedure is presented for fast and reliable
      characterization of the activated sludge composition. In previous research,
      relations between filament abundance and floc shape on the one hand, and the
      Sludge Volume Index on the other hand were sought. This work aims at
      demonstrating the use of the image analysis information as an indication for the
      amount of suspended solids in the effluent.

PMID- 16459791
TI  - Rethinking sewage treatment by enhancing primary settling with low-dosage lime.
AB  - This work presents a thorough fractionation of COD in raw sewage, followed by
      pilot plant coagulation tests with low-dosage lime (pH 9). Through a physical
      separation (sieving and crossflow filtration) total COD in the raw sewage was
      partitioned among eight size fractions in the range of 150-0.02 microm. In
      addition, respirometric tests were performed to measure the biodegradability of
      the different size fractions. More than 60% of COD was associated with settleable
      and supracolloidal particles (size > 1 microm), which are characterised by slow
      biodegradability. Coagulation with lime increased COD removal efficiencies in the
      primary treatment from typical 30-35%, up to 65-70%, suggesting that lime may
      induce the almost complete removal of the slowly settling, slowly biodegradable
      supracolloidal particles in the primary treatment. On the basis of these results
      a non-conventional sewage treatment scheme is proposed, considering that there is
      plenty of space for improving primary treatment efficiency through sewage
      coagulation. Higher primary treatment efficiency may present several advantages,
      including lower aeration energy in the subsequent biological unit and higher
      energy recovery from sludge digestion.

PMID- 16459793
TI  - A pilot study on accelerated sludge degradation by a high-concentration membrane
      bioreactor coupled with sludge pretreatment.
AB  - A new sludge treatment process combining a high MLSS membrane bioreactor with
      sludge pretreatment techniques was studied in pilot-scale experiments. The
      membrane bioreactor (MBR) was adopted for high efficiency aerobic digestion. The
      combination of alkaline-ozone treatment of the mixed liquor in the MBR reactor
      accelerated the biodegradation process by enhancing biodegradability of the
      sludge. The hydraulic retention time (HRT) of the reactor was set as 3.1 days and
      the DO level was 1 mg/L on average. After 5 months of operation, the accumulative
      total solids reduction was more than 70%. Removal efficiency of volatile solids
      and non-volatile solids were 76% and 54%, respectively. It was found that a
      considerable portion of the non-volatile solids was dissolved into ions and then
      flushed out with the effluent. Also, about 41% and 28% of T-N and T-P in the raw
      sludge were removed although no biological nutrient removal process was adopted.
      The experiment was run smoothly without significant membrane fouling, even at the
      relatively high levels of MLSS concentration (11,000-25,000 mg/L). It is
      concluded that the newly proposed process can significantly increase the sludge
      reduction efficiency with much shorter retention times.

PMID- 16459794
TI  - A new approach to improve sludge dewatering using a semi-continuous hydraulic
      press system.
AB  - In future, it will be necessary to incinerate an increasing proportion of the
      sludge produced by public wastewater treatment. In this context, equipment for
      more effective dewatering of sewage sludge is required. A hydraulic press system
      (Bucher HP) which has been used to date in the food industry could represent an
      alternative to the sludge dewatering systems currently used. The basic
      suitability of this press system was demonstrated in comprehensive industrial
      scale trials at the Glarnerland STP (Switzerland). Dry solids contents of up to
      43% were measured in the pressed sludge. Currently, the optimization of
      individual process parameters is being investigated in a pilot plant at the
      Schwelm STP operated by Wupperverband (Germany).

PMID- 16459795
TI  - Improvement of the thickening and dewatering characteristics of activated sludge
      by electroflotation (EF).
AB  - The performances of electroflotation (EF) on the thickening of activated sludge
      were investigated using laboratory scale batch flotation reactors. Four activated
      sludges including bulking sludges were tested. After 30 minutes of EF operation,
      57-84% of sludge volume reduction could be achieved by EF, while only about 1.5
      14% could be obtained by gravity thickening for the same period. After thickening
      the effluent water quality in terms of TCOD, SS, and turbidity was improved by EF
      operation for all sludge samples. In addition, the EF thickened sludge showed
      much better dewaterability both in SRF and cake solid content. It is induced that
      the air bubbles entrapped in the thickened sludge play a key role in the observed
      dewaterbility improvement.

PMID- 16459796
TI  - Thermal hygienization of excess anaerobic sludge: a possible self-sustained
      application of biogas produced in UASB reactors.
AB  - The main current trends in final disposal of sludge from Wastewater Treatment
      Plants (WTP) include: safe use of nutrients and organic matter in agriculture,
      sludge disinfection and restricted use in landfill. As to sludge hygienization,
      helminth eggs have been used as a major parameter to determine the effectiveness
      of such process, and its inactivation can be reached by means of thermal
      treatment, under varying temperature and other conditions. In such context, the
      objective of this research was to determine how effectively biogas produced in
      UASB reactors could be used as a source of calorific energy for the thermal
      hygienization of excess anaerobic sludge, with Ascaris lumbricoides eggs being
      used as indicator microorganisms, and whether the system can operate on a self
      sustained basis. The experiments were conducted in a pilot-scale plant comprising
      one UASB reactor, two biogas holders and one thermal reactor. The investigation
      proved to be of extreme importance to developing countries, since it leads to a
      simplified and fully self-sustainable solution for sludge hygienization, while
      making it possible to reuse such material for agricultural purposes. It should be
      also noted that using biogas from UASB reactors is more than sufficient to
      accomplish the thermal hygienization of all excess sludge produced by this
      system, when used for treating domestic sewage.

PMID- 16459797
TI  - Understanding the mechanisms of thermal disintegrating treatment in the reduction
      of sludge production.
AB  - Among the technologies aimed at reducing sludge production, the combination of
      thermal treatment at 95 degrees C of sludge and the activated sludge process is a
      promising route. The feasibility of such a combined process is demonstrated (up
      to 60% sludge reduction) and the impacts of operating conditions on its
      efficiency are presented. Major emphasis was put on understanding the complex
      phenomena occurring within the thermal treatment: release and biodegradability of
      sludge organic matter, impact on the biological activity (decay, maintenance
      requirements, etc.). These effects were taken into account for the development of
      an ASM1-based model. Comparison between the modeling approach and experimental
      data (continuous and batch) showed that thermal treatment had three major issues
      partly explaining the reduction of sludge production: (i) a low release of
      organics; (ii) an immediate and reversible biological inactivation associated
      with additional maintenance energy requirements; and (iii) a potential inert
      production.

PMID- 16459798
TI  - The Ruhrverband sewage sludge disposal concept in the conflict between European
      and German standards and regulations.
AB  - The Ruhrverband, acting as a water association responsible for integrated water
      resources management within the entire natural river basin of the Ruhr, operates
      a network of 83 wastewater treatment plants (WWTPs) and connected sludge disposal
      facilities. According to German regulations, the disposal of sewage sludge
      containing more than 5% of organic dry solids will be prohibited as of 1 June
      2005. In Germany, the only future alternative to incineration will be the
      agricultural utilization of sludge. However, this way of sludge disposal is
      presently the subject of critical discussions in Germany because of the organic
      and inorganic toxic substances, which may be contained in sewage sludge, despite
      the fact that very stringent standards are to be met by agricultural uses. On the
      other hand, application of sewage sludge to agricultural land is explicitly
      supported by the European Sewage Sludge Directive 86/278/EEC. In the face of this
      controversial situation the Ruhrverband has initiated, in 2000, the development
      of a comprehensive and sustainable sludge and waste disposal concept for all
      wastewater facilities it operates in the entire Ruhr River Basin. The concept
      includes de-central sludge digestion and dewatering and subsequent transport to
      two central sludge incineration plants. It is expected that in future not more
      than 5% of all sludges produced in Ruhrverband's WWTPs will be used in
      agriculture. That means, the major part of 95% will have to be incinerated.

PMID- 16459799
TI  - Minimisation of excess sludge production in a WWTP by coupling thermal hydrolysis
      and rapid anaerobic digestion.
AB  - In many cases, reducing sludge production could be the solution for wastewater
      treatment plants (WWTP) that here difficulty evacuating the residuals of
      wastewater treatment. The aim of this study was to test the possibility of
      minimising the excess sludge production by coupling a thermal hydrolysis stage
      and an anaerobic digestion with a very short HRT. The tests were carried out on a
      2,500 p.e. pilot plant installed on a recycling loop between the clarifier and
      the actived sludge basin. The line equipped with the full scale pilot plant
      produced 38% TSS less than the control line during a 10 week period. Moreover,
      the rapid anaerobic digestion removed, on average, more than 50% of the total COD
      load with a hydraulic retention time (HRT) of 3 days. Lastly, the dryness of the
      remaining excess sludge, sanitised by the thermal hydrolysis, was more than 35%
      with an industrial centrifuge. This combination of thermal hydrolysis and rapid
      anaerobic digestion equally permits a significant gain of compactness compared to
      traditional anaerobic digesters.

PMID- 16459800
TI  - The discharged excess sludge treated by Oligochaeta.
AB  - To overcome unstable worm growth, a new worm-reactor was developed for
      oligochaete growth. The bench scale of this worm-reactor was used to treat the
      discharged excess sludge from a pilot activated sludge system, and experiments
      were carried out to investigate the sludge reduction induced by Oligochaeta. Due
      to difficult getting free-swimming worms such as Aeolosoma hemprichicii and Nais
      elinguis, Tubifex tubifex was thus selected and inoculated in Reactor 1 at the
      start-up phase except the control reactor (Reactor 2). Tubifex occurred in
      Reactor 1 throughout the operation period after its inoculation, and mainly
      attached on the carriers and aggregated on the bottom of the worm-reactor. Free
      swimming worms such as Aeolosoma hemprichicii, Nais elinguis, and Aulophorus
      furcatus were found in both reactors since the 35th day. Microscopic
      investigation showed that these free-swimming worms naturally produced in the
      pilot activated sludge system, and entered into both reactors along the
      discharged sludge. Results clearly showed that the average sludge reduction in
      Reactor 1 was 59%, much higher than that in the control. The characteristics of
      sludge settling was improved by worm growth, but was not too much. High ammonia
      nitrogen concentration in influent sludge was toxic to worms, and then inhibited
      worm growth. Both the total inorganic nitrogen and phosphorus releases into
      effluent sludge were observed in Reactor 1, but such increases were not heavy.

PMID- 16459801
TI  - Integrated biological (anaerobic-aerobic) and physico-chemical treatment of
      baker's yeast wastewater.
AB  - The UASB reactor (35 degrees C) was quite efficient for removal of bulk COD (52
      74%) from simulated (on the basis of cultivation medium from the first separation
      process) general effluent of baker's yeast production (the average organic
      loading rates varied from 8.1 to 16 g COD/l/d). The aerobic-anoxic biofilter (19
      23 degrees C) can be used for removal of remaining BOD and ammonia from anaerobic
      effluents; however, it suffered from COD-deficiency to fulfil denitrification
      requirements. To balance COD/N ratio, some bypass (approximately 10%) of
      anaerobically untreated general effluent should be added to the biofilter feed.
      The application of iron (III)-, aluminium- or calcium-induced coagulation for
      post-treatment of aerobic-anoxic effluents can fulfil the limits for discharge to
      sewerage (even for colour mainly exerted by hardly biodegradable melanoidins),
      however, the required amounts of coagulants were relatively high.

PMID- 16459802
TI  - Advanced treatment of benzothiazole contaminated waters: comparison of O3, AC,
      and O3/AC processes.
AB  - Benzothiazole (BT) is a toxic and poorly biodegradable contaminant, usually found
      in wastewater from rubber related applications. This compound could be
      effectively eliminated using advanced treatment processes. This paper compares
      experimental results on detoxification systems based on ozone oxidation,
      activated carbon adsorption, and simultaneous adsorption-oxidation using ozone in
      the presence of activated carbon. The effect of pH (2-11), and the presence of
      radical scavengers (tert-butyl alcohol and sodium carbonate) on process rates and
      removal efficiencies are assessed at laboratory scale. The experimental system
      consisted of a 1 L differential circular flow reactor and an ozone generator
      rated at 5 g O3/h. Results show that ozone oxidation combined with activated
      carbon adsorption increases the overall BT oxidation rate with respect to the
      ozonation process and activated carbon adsorption. In the presence of free
      radical scavenger, only a 44% reduction in BT removal rate is observed in the
      simultaneous treatment, as compared with 72% when ozonation treatment is used,
      suggesting that BT oxidation reactions mainly take place on the activated carbon
      surface.

PMID- 16459803
TI  - Treatment of packaging board whitewater in anaerobic/aerobic biokidney.
AB  - Whitewater from production of packaging board was treated in a combined
      anaerobic/aerobic biokidney, both in laboratory scale and pilot plant
      experiments. Both the laboratory experiments and the pilot plant trial
      demonstrate that a combined anaerobic/aerobic process is suitable for treating
      whitewater from a packaging mill. It is also possible to operate the process at
      the prevailing whitewater temperature. In the laboratory under mesophilic
      conditions the maximal organic load was 12 kg COD/m3*d on the anaerobic reactor
      and 6.7 kg COD/m3*d on the aerobic reactor. This gave a hydraulic retention time,
      HRT, in the anaerobic reactor of 10 hours and 2 hours in the aerobic reactor. The
      reduction of COD was between 85 and 90% after the first stage and the total
      reduction was between 88 to 93%. Under thermophilic conditions in the laboratory
      the organic load was slightly lower than 9.6 COD/m3*d and between 10 and 16
      COD/m3*d, respectively. The HRT was 16.5 and 3.4 hours and the removal was around
      75% after the anaerobic reactor and 87% after the total process. For the pilot
      plant experiment at a mill the HRT in the anaerobic step varied between 3 and 17
      hours and the corresponding organic load between 4 and 44 kg COD/m3*d. The HRT in
      the aerobic step varied between 1 and 6 hours and the organic load between 1.5
      and 26 kg COD/m3*d. The removal of soluble organic matter was 78% in the
      anaerobic step and 86% after the combined treatment at the lowest loading level.
      The removal efficiency at the highest loading level was about 65% in the
      anaerobic step and 77% after the aerobic step. In the pilot plant trial the
      removal efficiency was not markedly affected by the variations in whitewater
      composition that were caused by change of production. The variations, however,
      made the manual control of the nutrient dosage inadequate and resulted in large
      variations in effluent nutrient concentration. This demonstrates the need for an
      automatic nutrient dosage system. The first step towards such a system was to
      evaluate two different on-line instruments. Both had severe stability problems,
      which made them unsuitable as parts in a system for control of the nutrient
      dosage.

PMID- 16459804
TI  - Production integrated treatment of textile wastewater by closing raw material
      cycles.
AB  - A method for the in-house treatment of partial wastewater flows and the recycling
      of treated process water into the textile finishing process was developed in
      order to recycle effluents from textile finishing industry and feed them back
      into the production process. The method is based on a two-stage biological
      anaerobic-aerobic process to split colouring wastewater agents and to degrade
      organic substances contained in the water as well as a chemical stage to remove
      the remaining color of the water with the help of ozone. In the framework of a
      research and development project a demonstration plant for a treatment capacity
      of 1440 m3 per working day was installed and started in a textile finishing
      company. At the plant, a wastewater flow and a recycling flow are treated
      separately in two different treatment lanes. Approximately 40% of the total
      wastewater flows, i.e. 576 m3/d are treated in the wastewater lane, and a maximum
      of 60% of total wastewater, i.e. 864 m3/d are treated in the recycling lane.
      Thanks to the preliminary treatment of wastewater flows, which are discharged
      into the municipal sewage works, a reduction of average COD levels in the sewage
      works effluents could be achieved.

PMID- 16459805
TI  - Advanced oxidation of commercial textile biocides in aqueous solution: effects on
      acute toxicity and biomass inhibition.
AB  - In the present study, the decomposition of two biocides used in the textile
      finishing process with Advanced Oxidation Processes (AOPs) has been studied.
      Different AOPs, i.e O3/OH-, TiO2/UV-A and Fe2+/H2O2 have been used representing
      mutually combined components of the chemically and photochemically driven
      advanced oxidation systems. The course of reaction was examined by changes in
      chemical oxygen demand (COD), total organic carbon (TOC) and acute toxicity
      towards the water flea Daphnia magna (assessed in terms of the effective dilution
      ratio LD50). Particular attention has been paid to determine the inhibitory
      effect of raw and ozonated biocides on biological activated sludge consortium at
      concentrations typically encountered in textile finishing effluents. Significant
      oxidation and mineralization of both biocides could be achieved employing
      ozonation at pH = 11.5 and heterogeneous photocatalysis (TiO2/UV-A) at pH = 5.0,
      whereas Fenton's reagent appeared to be less effective in COD and acute toxicity
      abatement.

PMID- 16459806
TI  - Electron beam treatment of textile dyeing wastewater: operation of pilot plant
      and industrial plant construction.
AB  - A pilot plant for treating 1000 m3/day of dyeing wastewater with e-beam has been
      constructed and operated since 1998 in Daegu, Korea together with the biological
      treatment facility. The wastewater from various stages of the existing
      purification process has been treated with an electron beam in this plant, and it
      gave rise to elaborating the optimal technology of the electron beam treatment of
      wastewater with increased reliability for instant changes in the composition of
      wastewater. Installation of the e-beam pilot plant resulted in decolorizing and
      destructive oxidation of organic impurities in wastewater, appreciable reduction
      of chemical reagent consumption, in reduction of the treatment time, and in
      increase in the flow rate limit of existing facilities by 30-40%. Industrial
      plant for treating 10,000 m3/day each, based upon the pilot experimental result,
      is under construction and will be finished by 2005. This project is supported by
      the International Atomic Energy Agency (IAEA) and Korean Government.

PMID- 16459807
TI  - High performance biofilm process for treating wastewater discharged from coal
      refining plants containing nitrogen, cyanide and thiocyanate.
AB  - Wastewater discharge from coal refining plants contains a number of biologically
      toxic compounds; 2000-2500 mg/l of COD of which 40% is composed of phenol, 100
      400 mg/l of thiocyanate, 10-40 mg/l of cyanide, 100-250 mg/l of NH4+-N and 150
      300 mg/l of total nitrogen. In order to treat this kind of high strength
      wastewater, we have developed a high performance biofilm process using fluidizing
      bio-carriers of the tube chip type. The fluidizing biofilm carriers are made of a
      composite of polyethylene and several inorganic materials, whose density is
      controlled at 0.97-0.98 g/ml. The fluidizing biofilm carriers show sound
      fluidization characteristics inside bioreactors. The wastewater is treated using
      three consecutive series reactors in oxic-anoxic-oxic arrangement. Each reactor
      is charged with the fluidizing biofilm carriers of 50 vol%. Furthermore, newly
      cultured active microorganisms for the thiocyanate biodegradation are added in
      the biofilm process. At total hydraulic retention time of 2.2 days, this process
      can achieve steady state removal efficiencies: COD, 99%; thiocyanate, 99%; NH4+
      N, 99% and total nitrogen, 90%.

PMID- 16459808
TI  - Aerobic granulation in a sequencing batch reactor (SBR) for industrial wastewater
      treatment.
AB  - Aerobic granulation seems to be an a attractive process for COD removal from
      industrial wastewater, characterised by a high content of soluble organic
      compounds. In order to evaluate the practical aspects of the process, comparative
      experimental tests are performed on synthetic and on industrial wastewater,
      originating from pharmaceutical industry. Two pilot plants are operated as
      sequencing batch bubble columns. Focus was put on the feasibility of the process
      for high COD removal and on its operational procedure. For both wastewaters, a
      rapid formation of aerobic granules is observed along with a high COD removal
      rate. Granule characteristics are quite similar with respect to the two types of
      wastewater. It seems that filamentous bacteria are part of the granule structure
      and that phosphorus precipitation can play an important role in granule
      formation. For both wastewaters similar removal performances for dissolved
      biodegradable COD are observed (> 95%). However, a relatively high concentration
      of suspended solids in the outlet deteriorates the performance with regard to
      total COD removal. Biomass detachment seems to play a non-negligible role in the
      current set-up. After a stable operational phase the variation of the
      pharmaceutical wastewater caused a destabilisation and loss of the granules,
      despite the control for balanced nutrient supply. The first results with real
      industrial wastewater demonstrate the feasibility of this innovative process.
      However, special attention has to be paid to the critical aspects such as granule
      stability as well as the economic competitiveness, which both will need further
      investigation and evaluation.

PMID- 16459809
TI  - The effect of colloid stability of wastewater treatment plants effluent on
      nanofiltration performance.
AB  - Laboratory-scale filtration tests utilizing wastewater treatment plants (WWTP)
      effluent were conducted to investigate fouling and filtration behaviour,
      especially the influence of colloidal stability on nanofiltration performance.
      Acidification and coagulant dosage were used to create unstable colloidal
      conditions. Colloidal stability of the effluent was analysed on by zeta potential
      measurements. A statistical design method, full factorial design with blocking,
      has been used to account for effluent composition variations and to account for
      interaction between experimental parameters. The results show a high correlation
      between unstable colloidal natural organic matter and the formation of dense
      fouling layers. The reversibility of the fouling process was shown to be
      independent from colloidal stability. Irreversible fouling was show to be
      promoted by mild acidic (pH 5) effluent conditions, whereas coagulant addition
      showed an increase in the reversibility of the fouling.

PMID- 16459810
TI  - Calibrating a side-stream membrane bioreactor using Activated Sludge Model No. 1.
AB  - Membrane bioreactors (MBRs) are attracting global interest but the mathematical
      modeling of the biological performance of MBRs remains very limited. This study
      focuses on the modeling of a side-stream MBR system using the Activated Sludge
      Model No. 1 (ASM1), and compares the results with the modeling of traditional
      activated sludge processes. ASM1 parameters relevant for the long-term biological
      behaviour in MBR systems were calibrated (i.e. Y(H) = 0.72 gCOD/gCOD, Y(A) = 0.25
      gCOD/gN, b(H) = 0.25 d(-1), b(A) = 0.080 d(-1) and f(p) = 0.06), and generally
      agreed with the parameters in traditional activated sludge processes, with the
      exception that a higher autotrophic biomass decay rate was observed in the MBR.
      Influent wastewater characterization was proven to be a critical step in model
      calibration, and special care should be taken in characterizing the inert
      particulate COD (X(I)) concentration in the MBR influent. It appeared that the
      chemical-biological method was superior to the physical-chemical method. A
      sensitivity analysis for steady-state operation and DO dynamics suggested that
      the biological performance of the MBR system (the sludge concentration, effluent
      quality and the DO dynamics) are very sensitive to the parameters (i.e. Y(H),
      Y(A), b(H), b(A) micro(maxH) and micro(maxA), and influent wastewater components
      (X(I), S(s), X(s) and S(NH)).

PMID- 16459811
TI  - Effects of complete sludge retention on biomass build-up in a membrane
      bioreactor.
AB  - The work reports the main results of an experimental activity aimed at evaluating
      the performance of a membrane bioreactor with complete sludge retention and the
      characteristics of its biomass. The bench scale system was started-up without any
      sludge inoculum and fed on real municipal sewage in order to favour biomass
      selection based on the imposed operating conditions. Process performance was
      evaluated in terms of COD removal (above 90% on average) and nitrification under
      two pre-determined volumetric loading rates (0.8 and 1.7 gCOD L(react)(-1), d(-1)
      on average). The biomass was evaluated in terms of growth, accumulation of inert
      solids, and bacterial activity. The latter was measured through respirometric
      tests. The results showed that the suspended solids concentrations (SS) under
      equilibrium were proportional to the volumetric loading rates in both the
      experimental periods considered and a relationship between these two parameters
      was proposed. Also, the organic loading rates reached the same equilibrium value
      of 0.12 gCOD gTSS(-1) d(-1) in the two periods. Moreover, the system showed very
      limited sludge production under equilibrium conditions (0.12 gVSS gCOD(rem)(-1)
      and low biomass activity, although it readily responded to load variations.

PMID- 16459812
TI  - Treatment of nanosized TiO2-containing wastewater by simultaneous
      electrocoagulation/electrofiltration.
AB  - In this work, a simultaneous electrocoagulation/electrofiltration (EC/EF)
      treatment module was employed to treat nanosized TiO2-containing wastewater.
      Nanosized TiO2-containing wastewater was obtained and treated by a self-designed
      EC/EF treatment module. To evaluate the performance of this novel treatment
      module, the effects of electric field strength (EFS), transmembrane pressure
      (TMP), and crossflow velocity (CV) on permeate qualities were investigated.
      Permeate qualities of concern included pH, turbidity, conductivity, chemical
      oxygen demand (COD), and total organic carbon (TOC). A full factorial design of
      experiments was adopted in this work. First, by keeping TMP and CV constant the
      effects of EFS on permeate qualities were studied. In this set of testing, it was
      noticed that an application of electric field greatly increased the filtration
      rate, which was further influenced by the magnitude of EFS. In all cases, the
      filtration rate decreased as the treatment time elapsed due mainly to fouling of
      the membrane. Further tests were conducted to study the effects of TMP on
      permeate qualities by keeping EFS and CV constant. Finally, the effects of CV on
      permeate qualities were studied by keeping EFS and TMP constant. It was found
      that the optimal operating conditions would be electric field strength of 166.7
      V/cm, transmembrane pressure of 1 kgf/cm2, and crossflow velocity of 0.22cm/s.
      Under such conditions, permeate would have the following qualities: (1) pH, 6.32;
      (2) turbidity, 2.41 NTU; (3) conductivity, 15.11 microS/cm; (4) COD, 100.0 mg/L;
      and (5) TOC, 512.6 mg/L.

PMID- 16459813
TI  - Performance improvement of hybrid membrane bioreactor with PAC addition for water
      reuse.
AB  - A study was carried out on a hybrid (AS-SBF) membrane bioreactor (HMBR) for the
      municipal wastewater reclamation and reuse at Chengfengzhuang WWTP in Daqing
      City, Heilongjiang Province. It was found that the effects of DO and water
      temperature on performance of the HMBR was significant. Under the conditions of
      water temperature in range of 10-14 degrees C, pH of 6.6- 7.0, DO of 4-6 mg/l and
      HRT of 7 h, the HMBR exhibited removal efficiencies for CODcr, BOD5, NH3-N and TN
      of 96.7%, 98.9%, 93.7% and 60.5% respectively. The turbidity of effluent from
      HMBR was below 1 NTU. The effluent of HMBR meets the standard of wastewater
      reclamation for oil exploitation. PAC was added into the bioreactor at the second
      operating stage, in order to further research parameters variation. The flux was
      improved by 53.2%, compared to the membrane without PAC-addition, due to
      formation of a PAC pre-coat layer on the membrane surface, with lots of
      advantages such as larger granules, higher porosity, non-compressibility, higher
      filterability and easy removal, compared with pure biomass layer. In addition,
      the performance of HMBR was further improved, due to adsorption and degradation
      of SMPs, the average removal of CODcr and TN was further improved by 5.1% and
      13.5% respectively. Biomass in the HMBR was quantitatively measured, of which the
      biofilm played a major role in pollutants removal.

PMID- 16459814
TI  - Reduction of wastewaters and valorisation of by-products from "Serpa" cheese
      manufacture using nanofiltration.
AB  - Second cheese whey (SCW) is a by-product of cheese and curd cheese production
      that is usually not recovered and therefore contributes substantially to the
      negative environmental impact of the cheese manufacture plants. Membrane
      technology, namely nanofiltration (NF), is used in this work for the recovery of
      SCW organic nutrients, resulting from "Serpa" cheese and curd production. The SCW
      is processed by NF to recover a rich lactose fraction in the concentrate and a
      process water with a high salt content in the permeate. The permeation
      experiments were carried out in a plate and frame NF unit, where two NF membranes
      (NFT50 and HR-95-PP) were characterized and tested. The NF permeation experiments
      were performed accordingly with two different operation modes: total
      recirculation and concentration. In order to select the best membrane and
      operating pressure for the SCW fractionation, total recirculation experiments
      were carried out. After the membrane selection, the concentration experiments
      showed that the selected membrane (NFT50) at 30 bar allows a water recovery of
      approximately 80%, concentrating the second cheese whey nutrients approximately 5
      times. Therefore, the NF operation can successfully reduce the wastewater organic
      load and simultaneously contribute to the valorisation of the cheese and curd
      cheese manufacture by-products.

PMID- 16459816
TI  - Optimization of operational factors of a membrane bioreactor with gravity drain.
AB  - A new membrane bioreactor with gravity drain for municipal wastewater treatment
      was tested and its operational factors were investigated in this study. These
      factors include pressure head, MLSS, aeration intensity (an air flow rate per
      unit floor area) and temperature. Results of batch experiments showed that a
      critical pressure head of the MBR was 0.85-1.5 m-H2O. At a pressure head of 0.85
      m-H2O, statistical analysis of batch experiments showed that aeration intensity
      significantly affected membrane flux, and the MLSS had no impact on membrane flux
      under a temperature of 22.0 +/- 1.0 degrees C. Results of the long-term
      continuous experiment showed that temperature significantly affected membrane
      flux. The impact of temperature on membrane flux in this case was about 4-10
      times of that analyzed by using a classical cake layer model. During this
      experiment, the average removal efficiencies of COD, BOD5 and NH4+-N were over
      85%, 97% and 94%, respectively.

PMID- 16459815
TI  - Characterization of sludge structure and activity in submerged membrane
      bioreactor.
AB  - Sludge characteristics of a submerged membrane bioreactor (MBR) and an activated
      sludge process (AS) were compared, during a first phase at the same operating
      conditions (low MLSS and conventional SRT) and in a second phase with a high
      sludge retention time (SRT) in the membrane bioreactor. During the first phase, a
      bimodal flocs size distribution was observed in the MBR with simultaneously a
      macro-flocs population (240 microm) bigger than the flocs of activated sludge due
      to the absence of recirculating pump, and also more microflocs (1 to 15 microm)
      and free suspended cells retained by the membrane. It is shown that the membrane
      leads to an accumulation of proteins and polysaccharides in the sludge
      supernatant which is probably responsible for the high fouling propensity of the
      sludge during the starting period of MBR. These compounds are partially degraded
      after 50 to 60 days of operation. In the first phase respirometric experiments
      didn't demonstrate a significant difference in the maximal removal rates of
      either MBR or AS biomass (with excess substrate), except in the dynamic period
      during which the membrane retention gave an advantage by increasing the biomass
      activity. On the other hand, the respirometry shows that the half saturation
      constant for nitrification was significantly higher in the MBR process,
      suggesting higher substrate transfer limitation. During the last phase, it is
      shown that an increase of SRT from 9 to 106 days leads to a diminution of average
      macro-flocs size in the MBR from about 240 to 70 microm. With the SRT increase,
      modification in the organic compounds is also observed (proteins, polysaccharides
      and COD) in the sludge supernatant. Increasing the SRT from 9 to 40 days seems to
      slightly reduce the level of organic compounds (probable biodegradation), but the
      concentrations increased when SRT changes from 40 days to 106 days (probable
      accumulation of non biodegradable compounds).

PMID- 16459817
TI  - Membrane bioreactor versus conventional activated sludge system: population
      dynamics of nitrifiers.
AB  - Although membrane bioreactors have attracted increasing attention in recent
      years, little research has been undertaken on the influence of the membrane
      separation on the microbial community composition. This paper compares the
      startup behaviour and the performance of the subsequent eight months of a
      membrane bioreactor with a conventional activated sludge pilot plant. Both plants
      were operated in parallel at the same sludge age and treated the same domestic
      wastewater. The identification of the nitrifying community composition using
      fluorescent in situ hybridization revealed only minor differences between the two
      reactors for both ammonia-oxidizing bacteria and nitrite-oxidizing bacteria.
      Accordingly, both systems exhibited the same maximum nitrification rates.
      Confocal laser scanning microscopy showed that the aggregates formed by
      nitrifying bacteria were located mostly in the inner part of the flocs and were
      overgrown by heterotrophic bacteria. It is concluded that the membrane separation
      itself does affect neither the nitrifying community composition nor the
      nitrification performance. However, impacts on kinetic parameters are emphasized.

PMID- 16459818
TI  - Baffled membrane bioreactor (BMBR) for advanced wastewater treatment: easy
      modification of existing MBRs for efficient nutrient removal.
AB  - In this study, a novel membrane bioreactor (MBR) in which nitrification and
      denitrification simultaneously proceed in a single reaction chamber is proposed
      for advanced municipal wastewater treatment. Anoxic/aerobic environments are
      alternatively created in the proposed MBR by inserting baffles inside the
      membrane chamber. The performance of the proposed baffled membrane bioreactor
      (BMBR) was examined at an existing municipal wastewater treatment facility based
      on long-term operation. Although the procedure was simple, insertion of the
      baffles actually created the alternative anoxic/aerobic environments in the
      chamber at a constant interval and showed a great improvement in the nutrient
      removal. The insertion did not cause any adverse effect on membrane permeability.
      In this study, almost complete elimination of NH4+-N was observed while around 8
      mg/L of NO(3-)-N was detected in the treated water. The modification proposed in
      this study can immediately be applied to most existing MBRs and is highly
      recommended for more efficient wastewater treatment.

PMID- 16459819
TI  - Simultaneous nitrification and de-nitrification in MBR.
AB  - Experiments have been carried out to get an understanding of the effect of DO,
      C/N ratio and pH on the performance of a bench scale membrane bioreactor (MBR) in
      simultaneous nitrification and denitrification. It was found that under the
      conditions of MLSS in the range of 8000-9000 mg/L and temperature of water in the
      MBR of 24 degrees C, influent COD and NH3-N in the range of 523-700 mg/L and
      17.24-24 mg/L respectively, the removals of COD, NH3-N and TN were 98%, 99% and
      60%; 96.5%, 0,98% and 75%; 96%, 95% and 92%; 90%,70% and 60% respectively at DO
      of 6, 3, 1 and 0.5 mg/L. It was also found that the changes in C/N ratio and pH
      in a certain range have a slight effect on COD removal but have significant
      influence on the removal of NH3-N and TN. The results showed that only under the
      conditions that each ecological factor was maintained relatively steadily,
      simultaneous nitrification and de-nitrification proceeded smoothly. It was found
      that when C/N ratio was 30, the influent pH 7.2, the temperature of water in MBR
      24 degrees C and DO 1 mg/L, as optimum conditions, the removals of COD, NH3-N and
      TN were 96%, 95% and 92% respectively. In addition, mechanism research on
      simultaneous nitrification and de-nitrification in MBR has been conducted as
      well.

PMID- 16459820
TI  - Biological nutrient removal in simple dual sludge system with an UMBR (upflow
      multi-layer bioreactor) and aerobic biofilm reactor.
AB  - In this study, a simple dual sludge process was developed for small sewage
      treatment. It is a hybrid system that consists of upflow multi-layer bioreactor
      (UMBR) as anaerobic and anoxic reactor with suspended growth microorganisms and
      post aerobic biofilm reactor with inclined plates. UMBR is a multifunction
      reactor that acts as primary sedimentation tank, anaerobic reactor, anoxic
      reactor, and thickener. The sludge blanket in the UMBR is maintained at a
      constant level by automatic control so that clear water (30 mg-SS/L) can flow
      into the post aerobic biofilm reactor. It leads to improving performance of the
      biofilm reactor due to preventing of excess microbial attachment on the media
      surface and no requirment for a large clarifier caused by low solid loading. The
      HRT in the UMBR and the aerobic biofilm reactor were about 5.8 h and 6.4 h,
      respectively. The temperature in the reactor during this study varied from 12.5
      degrees C to 28.3 degrees C. The results obtained from this study show that
      effluent concentrations of TCOD, TBOD, SS, TN, and TP were 29.7 mg/L, 6.0 mg/L,
      10.3 mg/L, 12.0 mg/L, and 1.8 mg/L, which corresponded to a removal efficiency of
      92.7%, 96.4%, 96.4%, 74.9%, and 76.5%, respectively. The sludge biomass index
      (SBI) of the excess sludge in the UMBR was about 0.55, which means that the
      sludge in the UMBR was sufficiently stabilized and may not require further
      treatment prior to disposal.

PMID- 16459822
TI  - Nitrification parameter measurement for plant design: experience and experimental
      issues with new methods.
AB  - Nitrification kinetics are important for process design, optimization, and
      capacity rating of activated sludge wastewater treatment plants. A Water
      Environment Research Foundation (WERF) project on Methods for Wastewater
      Characterization in Activated Sludge Modeling (WERF, 2003) focused significantly
      on the development of procedures for measuring the nitrifier maximum specific
      growth rate, micro(AUT). In addition, the importance of (and lack of data for)
      the nitrifier decay rate, b(AUT), was identified. This paper describes three
      bench-scale methods for measuring micro(AUT): the Low F/M SBR, Washout and High
      F/M methods. During the WERF project, the importance of pH and temperature
      control was investigated briefly; this paper summarizes further experimental work
      performed to address these issues. A summary of micro(AUT) measurements in a
      number of locations and using the different measurement techniques is provided.

PMID- 16459821
TI  - Outcomes of a 2-year investigation on enhanced biological nutrients removal and
      trace organics elimination in membrane bioreactor (MBR).
AB  - Two configurations of membrane bioreactors were identified to achieve enhanced
      biological phosphorus and nitrogen removal, and assessed over more than two years
      with two parallel pilot plants of 2m3 each. Both configurations included an
      anaerobic zone ahead of the biological reactor, and differed by the position of
      the anoxic zone: standard pre-denitrification, or post-denitrification without
      dosing of carbon source. Both configurations achieved improved phosphorus
      removal. The goal of 50 microgP/L in the effluent could be consistently achieved
      with two types of municipal wastewater, the second site requiring a low dose of
      ferric salt ferric salt < 3 mgFe/L. The full potential of biological phosphorus
      removal could be demonstrated during phosphate spiking trials, where up to 1 mg
      of phosphorus was biologically eliminated for 10 mg BOD5 in the influent. The
      post-denitrification configuration enabled a very good elimination of nitrogen.
      Daily nitrate concentration as low as 1 mgN/L could be monitored in the effluent
      in some periods. The denitrification rates, greater than those expected for
      endogenous denitrification, could be accounted for by the use of the glycogene
      pool, internally stored by the denitrifying microorganisms in the anaerobic zone.
      Pharmaceuticals residues and steroids were regularly monitored on the two
      parallel MBR pilot plants during the length of the trials, and compared with the
      performance of the Berlin-Ruhleben WWTP. Although some compounds such as
      carbamazepine were persistent through all the systems, most of the compounds
      could be better removed by the MBR plants. The influence of temperature, sludge
      age and compound concentration could be shown, as well as the significance of
      biological mechanisms in the removal of trace organic compounds.

PMID- 16459823
TI  - Importance and measurement of decay rate when assessing nitrification kinetics.
AB  - Nitrification kinetics are important for process design, optimization and
      capacity rating of activated sludge wastewater treatment plants. Assessment of
      nitrification behaviour historically has focused on measuring the nitrifier
      maximum specific growth rate, micro(AUT). Very little attention has been directed
      at the of nitrifier organism rate has been assumed negligible. However, incorrect
      assessment of decay rate leads to errors in the micro(AUT) estimate; the
      magnitude of the error depends on the micro(AUT) measurement method employed.
      This paper illustrates why decay rate is important when measuring micro(AUT), and
      that the decay rate is significant. The paper also explains why measurement
      methods for nitrifier decay may have underestimated the decay rate. Results from
      an experiment incorporating improvements to previously suggested methods and data
      analysis are presented.

PMID- 16459824
TI  - Comparative study on the bio-electrochemical denitrification equipped with a
      multi-electrode system.
AB  - Three biofilm-electrode reactors (BERs) with multiple cathodes were applied to
      investigate the effect of electrode configuration and flow direction on
      denitrification under laboratory-scale conditions. The distribution of nitrate,
      DO and pH varied among applied BERs, as a consequence of a different electrode
      position in the reactors, bringing about a difference in the performance. Flow
      through configuration of electrodes with a downstream anode appears to be the
      most suitable configuration since nitrite did not accumulate in the effluent only
      in this experiment and the current-denitrification efficiency at low current
      densities was high. Thus, it is recommended for a low-loading operation.

PMID- 16459825
TI  - Nitrogen removal from piggery waste using the combined SHARON and ANAMMOX
      process.
AB  - Nitrogen removal in piggery waste was investigated with the combined SHARON
      ANAMMOX process. The piggery waste was characterized as strong nitrogenous
      wastewater with very low C/N ratio. For the preceding SHARON reactor, ammonium
      nitrogen loading and conversion rates were 0.97 kg NH4-N/m3 reactor/day and 0.73
      kg NH4-N/m3 reactor/day, respectively. Alkalinity consumption for ammonium
      conversion was 8.5 gr bicarbonate utilized per gram ammonium nitrogen converted
      to NO2-N or NO3-N at steady-states operation. The successive ANAMMOX reactor was
      fed with the effluent from SHARON reactor. Nitrogen loading and conversion rates
      were 1.36 kg soluble N/m3 reactor/day and 0.72 kg soluble N/m3 reactor/day,
      respectively. The average NO2-N/NH4-N removal ratio by ANAMMOX reaction was 2.13.
      It has been observed that Candidatus "Kuenenia stuttgartiensis" were dominated in
      the ANAMMOX reactor based on FISH analysis.

PMID- 16459826
TI  - Denitrification with polycaprolactone as solid substrate in a laboratory-scale
      recirculated aquaculture system.
AB  - A denitrification system based on the biodegradable polymer Poly-epsilon
      Caprolactone (PCL) was tested in a laboratory-scale recirculated aquaculture
      system with eels in comparison to a reference system without denitrification. The
      experiments were conducted with fluidized bed reactors in two parallel systems to
      examine the feasibility and performance of the process and to observe the
      condition of fishes by measuring weight gain during the test-period. The most
      evident effect of the system with denitrification was the low nitrate
      concentration compared with the untreated reference system. A further advantage
      was the stability of the pH in the systems with denitrification whereas pH of the
      untreated water decreased due to nitrification. All over the test-period the eels
      showed a similar weight gain in both systems.

PMID- 16459827
TI  - Applicability of an extant batch respirometric assay in describing dynamics of
      ammonia and nitrite oxidation in a nitrifying bioreactor.
AB  - Several techniques have been proposed for biokinetic estimation of nitrification.
      Recently, an extant respirometric assay has been presented that yields kinetic
      parameters for both nitrification steps with minimal physiological change to the
      microorganisms during the assay. Herein, the ability of biokinetic parameter
      estimates from the extant respirometric assay to adequately describe concurrently
      obtained NH4+-N and NO(2-)-N substrate depletion profiles is evaluated. Based on
      our results, in general, the substrate depletion profiles resulted in a higher
      estimate of the maximum specific growth rate coefficient, micro(max) for both
      NH4+-N to NO(2-)-N oxidation and NO(2-)-N to NO(3-)-N oxidation compared to
      estimates from the extant respirograms. The trends in the kinetic parameter
      estimates from the different biokinetic estimation techniques are paralleled in
      the nature of substrate depletion profiles obtained from best-fit parameters.
      Based on a visual inspection, in general, best-fit parameters from optimally
      designed complete respirograms provided a better description of the substrate
      depletion profiles than estimates from isolated respirograms. Nevertheless, the
      sum of the squared errors for the best-fit respirometry based parameters was
      outside the 95% joint confidence interval computed for the best-fit substrate
      depletion based parameters. Notwithstanding the difference in kinetic parameter
      estimates determined in this study, the different biokinetic estimation
      techniques still are close to estimates reported in literature. Additional
      parameter identifiability and sensitivity analysis of parameters from substrate
      depletion assays revealed high precision of parameters and high parameter
      correlation. Although biokinetic estimation via automated extant respirometry is
      far more facile than via manual substrate depletion measurements, additional
      sensitivity analyses are needed to test the impact of differences in the
      resulting parameter values on continuous reactor performance.

PMID- 16459828
TI  - Chemical denitrification for nitrogen removal from landfill leachate.
AB  - A new system that removes nitrogen from landfill leachate and other waste waters
      with similar properties has been proposed with nitritation (i.e. oxidation of
      ammonium to nitrite) of half of the influent ammonium followed by chemical
      denitrification with a reaction between equal amounts of ammonium and nitrite to
      form nitrogen gas. Chemical denitrification occurs at high concentrations and the
      reactions were studied in combination with a concentration step. Studied
      concentration methods were freezing/thawing and evaporation/drying. Chemical
      denitrification is well-known in inorganic chemistry and has been observed in
      natural systems. Studies in laboratory were focused on chemical denitrification
      and showed that nearly complete removal of soluble nitrogen can be obtained in
      evaporation/drying of water solutions or leachate with equal amounts of ammonium
      and nitrite. Freezing/drying was less efficient with a removal of about 50-60% at
      high initial concentrations. Chemical denitrification is much influenced by
      concentration, pH-value, temperature and some compounds in leachate have an
      inhibiting effect on the reaction. Factors as safety (ammonium nitrite as a salt
      is explosive above 60 degrees C) and possible side-reactions as formation of
      ammonia and nitrogen oxides must be carefully evaluated before use in full-scale.
      Conductivity is a suitable parameter to follow-up the chemical denitrification
      process.

PMID- 16459829
TI  - Partial nitrification of wastewater from an aminoplastic resin producing factory.
AB  - Nitrification via nitrite was studied in two aerobic reactors treating wastewater
      from an aminoplastic resin producing factory at HRT varying between 1.37-1.89 and
      2.45-3.63 days. Both eactors were fed with concentrations of 366, 450, 1099 and
      1899 mg N-NH4+/L. In general in the reactor operated at a lower HRT, the
      nitritation percentage decreased from 87.2 to 21.6%, while the nitratation
      percentage remained always lower than 2.5% (except in the last period) when the
      ammonium concentration was increased. This behaviour could be due to the
      inhibition of the ammonium and nitrite oxidation produced by high free ammonia
      concentrations up to 179.3 mg N-NH3/L. In the reactor operated at a higher HRT,
      the nitritation percentage decreased and the nitratation percentage increased
      from 88.6 to 39.6% and from 0.65 to 35.7%, respectively, due to an increase of
      the dissolved oxygen concentration from 0.76 to 1.02 mg O2/L. However, when
      ammonium was fed at a concentration of 1898.7 mg N-NH4+/L, the nitritation
      increased and the nitratation decreased, probably as a result of the accumulation
      of free ammonia up to 2.04 mg N-NH3/L, meaning that nitrite oxidizers were
      inhibited. Nitrite build-up was observed after each modification of ammonium
      concentration in the feed.

PMID- 16459830
TI  - Phosphorus removal from synthetic and municipal wastewater using spent alum
      sludge.
AB  - In the present study, phosphorus removal was studied using as coagulant spent
      alum sludge from a water treatment plant of EYDAP (Athens Water Supply and
      Sewerage Company) and compared to alum (Al2(SO4)3.18H2O), iron chloride
      (FeCl3.7H2O), iron sulfate (Fe2(S04).10H2O) and calcium hydroxide (Ca(OH)2) at a
      constant pH (equal to 6). The comparison was based on their efficiency to remove
      phosphorus in synthetic wastewater consisting of 10 mg/L P as potassium
      dihydrogen phosphate and 50 mg/L N as ammonium chloride, The experiments were
      carried out using a jar-test apparatus and the measurements were performed
      according to the Standard Methods for the Examination of Water and Wastewater.
      Pure alum, iron chloride and iron sulfate were much more efficient in phosphorus
      removal than the spent alum sludge but in the case of calcium hydroxide,
      phosphorus removal was very low in pH = 6. Specifically, orthophosphate were
      totally removed by alum using 15 mg/L as Al, by alum sludge using 75 mg/L as Al
      and by FeCl3.7H2O or Fe2(SO4).10H2O using 30 mg/L of Fe while in the case of
      calcium hydroxide P removal was actually zero. pH measurements showed that the
      uptake of phosphates is associated to the release of OH ions in the solution and
      that the end of P uptake is accompanied by the stabilization of pH. Finally this
      spent alum sludge was tested on municipal wastewater and proved to be effective
      as apart from phosphorus it was shown to remove turbidity and COD.

PMID- 16459831
TI  - Application of hydrothermal reaction for excess sludge reuse as carbon sources in
      biological phosphorus removal.
AB  - An application of hydrothermal reaction was investigated to reuse excess sludge
      as carbon sources for enhancement of biological phosphorus removal. Under the
      tested conditions, solubilization of treated excess sludge did not present much
      variation, sustaining around 65%, except the results obtained at 400 degrees C.
      Biodegradability of excess sludge was improved through its content change by the
      reaction, without much reduction of carbon contents even in 7 min. From the
      results of respirometric test, readily biodegradable substrate was found at 300
      degrees C. Then its portion of reaction products increased with increasing
      reaction temperature. In the readily biodegradable substrate, acetic and
      propionic acid, which are useful carbon sources for phosphorus accumulating
      microorganism under anaerobic condition, increased with increasing reaction
      temperature. Hydrothermal reaction might be accepted as suitable pretreatment
      method to treat excess sludge prior to biological treatment process. This
      technology also secures excess sludge reuse, enhancing biological phosphorus
      removal and improvement of biological treatment process.

PMID- 16459832
TI  - Phosphorus recycling in sewage treatment plants with biological phosphorus
      removal.
AB  - In this paper, phosphorus balances are calculated for the wastewater purification
      and sludge treatment stages for wastewater treatment plants (WWTPs) applying
      Enhanced Biological Phosphorus Removal (EBPR). The possible P-recovery potential
      is then estimated and evaluated regarding different locations along the process
      of wastewater purification and sludge treatment, taking the different phosphorus
      bonding forms into account. Caused by the more favourable bonding forms in the
      excess sludge as well as possibly also in the sludge ash a recovery of the
      phosphorus seems especially favoured for WWTPs with EBPR. The processes available
      for a P recycling are named, and special regard is given to the Phostrip-process,
      which is a possible recycling process already tested in practice. Further R&D
      demand consists in basic research regarding disintegration, fermentation or
      acidic total digestion of excess sludge followed by phosphorus precipitation
      including separation of the precipitates, MAP-precipitation and separation from
      digested sludge and on the ability to extract phosphorus and heavy metals from
      sewage sludge ash. These investigations are a precondition to enable purposeful
      process developments. At the present state the cost of recycled phosphorus earned
      from wastewater, sludge and ash, respectively, are a multiple higher than the
      costs for raw phosphate taking into account the suitable processes. Thus, up to
      now no phosphorus recycling with a defrayal of costs is possible. The future
      importance of phosphorus recycling will depend on the market price for raw
      phosphate, the recycling costs and, furthermore, on the general political
      framework.

PMID- 16459833
TI  - Chemical phosphorus removal model based on equilibrium chemistry.
AB  - Regulations in many regions of the world require total phosphorus (TP) levels
      lower than 0.10 mgP/L (100 microgP/L) in effluents, resulting in the need to
      achieve very low ortho-phosphate (OP) concentrations. Chemical precipitation is a
      widely used technology for controlling effluent OP discharge, either on its own
      or supplementing biological methods. The various chemical and physico-chemical
      mechanisms that result in extremely low residual OP levels are complex and depend
      on pH. In practice, engineering calculations frequently use an empirical
      precipitation model. This model requires pH as input and predicts the lowest
      achievable OP residual of 35 microgP/L at a narrow optimum pH of 6.9-7.0, when an
      excess of ferric is added. The model has been combined with a biokinetic and weak
      acid/base chemistry based pH model, to allow accurate prediction of pH, OP
      residuals and chemical sludge production. Analysis of effluent data from the Blue
      Plains plant shows that residuals as low as 10 microgP/L OP can be achieved
      regularly, over a wider pH range. The precipitation model was recalibrated to
      match the newly available data. Subsequently it was compared with a new,
      mechanistic precipitation model based on solubility and dissociation constants
      for actual chemical compounds. The need for more accurate measurement of
      extremely low OP concentrations and considering the role of organics, adsorption
      and coagulation in chemical phosphorus removal is demonstrated.

PMID- 16459834
TI  - Biochemistry of enhanced biological phosphorus removal and anaerobic COD
      stabilization.
AB  - Improved design strategies at BNR plants should include cost reductions so that
      the consumers and water authorities will be more willing to build EBPR plants
      instead of conventional activated sludge plants. Through efficient design, actual
      savings in construction and operation costs can be realized. For this reason,
      anaerobic stabilization of COD needs to be seriously considered during design for
      direct energy savings at the plants. The existence of anaerobic stabilization has
      been demonstrated through experimental work. Evaluation of operational data from
      existing plants has also indicated the definite presence of anaerobic
      stabilization at plants that include anaerobic zones for EBPR as part of their
      operation. By exploring the biochemical reactions taking place in EBPR process,
      particularly the involvement of the storage mechanisms for PHA, poly-P and
      glycogen storage, the potential mechanisms of the anaerobic stabilization of COD
      in EBPR systems was explored. The resultant balances pointed out the importance
      of glycogen metabolism in terms of conserving carbon and providing a sink for the
      reducing equivalents produced under aerobic conditions. This mechanism is
      different from those observed in anoxic-aerobic and conventional aerobic
      activated sludge systems, and appears to be at least partially responsible for
      the observed anaerobic stabilization of COD.

PMID- 16459835
TI  - Biological phosphorus and nitrogen removal with biological aerated filter using
      denitrifying phosphorus accumulating organism.
AB  - In order to accomplish the biological nutrient removal with a weak sewage at low
      temperature, a hybrid process consisted of anoxic denitrifying phosphorus
      accumulating organism (dPAO) and nitrifying biological aerated filter (BAF) was
      studied in both lab and field pilot plants with weak sewage. The biofilm BAF was
      used as a post-nitrification process that provided sufficient nitrate to
      suspended growth dPAO. The anoxic/BAF configuration could remove nitrogen and
      phosphorus appreciably compared to other BNR systems. The enhanced biological
      phosphorus removal (EBPR) was mainly occurred in anoxic zone of suspended growth
      reactor. It has been found that P removal efficiency of dPAO was enhanced with an
      addition of a short oxic zone in suspended reactors compared to that of without
      oxic zone. However, the degree of aerobic P uptake in oxic zone was far lower
      than anoxic P uptake. The operating results of field plant indicated that
      dPAO/BAF configuration successfully reduced the adverse temperature effects at
      lower than 15 degrees C.

PMID- 16459836
TI  - Biomass concentration and biofilm characteristics in high-performance fluidized
      bed biofilm reactors.
AB  - Two laboratory scale fluidized-bed biofilm reactors (FBBRs) were used to
      investigate the biomass concentration and the biofilm characteristics in a high
      performance FBBR used for the denitrification of exceptionally high-nitrate
      wastewater (1000 mg-N/L). Reported correlations by other workers for predicting
      the biomass concentration in FBBR were examined for their validity in comparison
      with the experimental results of this study and the best set of applicable
      correlations was recommended. The effects of the two main operational parameters,
      the superficial velocity and nitrogen loading rate on the biomass concentration
      in the FBBR were also studied. Correlations for the drag coefficient and the
      expansion index from the literature, together with the biofilm dry density
      correlation produced from this study were found to produce the best prediction of
      the FBBR biomass concentration compared to other reported correlations. The
      average biomass concentration in the FBBR decreased with the increase of the
      superficial velocity in the range of 45 to 65 m/h at all the applied nitrogen
      loadings (i.e. 6, 8, 12 and 16 kg-N/m3(bed).d).

PMID- 16459838
TI  - Over the short span of two months, we have experienced a renewed appreciation for
      the awesome power of nature.

PMID- 16459837
TI  - A comparison between the theory and reality of full-scale step-feed nutrient
      removal systems.
AB  - Capacity enhancement and volume reduction benefits of step-feeding fully aerobic
      bioreactors has been well documented. Application of step-feed technology to
      biological nutrient removal (BNR) systems, particularly those removing nitrogen
      alone or both nitrogen and phosphorus, is relatively new to the industry. In
      recent years, a number of full-scale step-feed facilities have been brought into
      service. This paper reviews nine full-scale step-feed biological nutrient removal
      systems--both nitrogen removal alone, and nitrogen and phosphorus removal. The
      objective is to compare the theoretical benefits of such systems with their
      actual operation. The predicted benefits of reduced bioreactor volume or
      increased process capacity, reduced energy usage, more robust nitrification
      performance, and the flexibility to tune (or de-tune) nitrification efficiency
      were verified in full-scale systems. Equations are also presented that may be
      used in the prediction of step-feed benefits. There are two primary drivers for
      considering a step-feed biological reactor system: 1. Reduced bioreactor volume
      for a defined capacity or performance or increased process capacity given a fixed
      bioreactor volume. 2. More robust nitrification performance. Full-scale operation
      of these step-feed nutrient removal systems provides a real world basis for the
      claimed benefits of step-feed operation. These systems have uniformly shown
      additional capacity. A number of them have also exhibited more robust
      performance, especially during storms. Where possible, side-by-side comparisons
      of full-scale step-feed systems with non-step-feed systems have exhibited greater
      process reliability and flexibility.

PMID- 16459839
TI  - Microcystins (cyanobacterial toxins) in surface waters of rural Bangladesh: pilot
      study.
AB  - In Bangladesh the exposure of millions of inhabitants to water from (shallow)
      tube wells contaminated with high geogenic loads of arsenic is a major concern.
      As an alternative to the costly drilling of deep wells, the return to the use of
      surface water as a source of drinking water is considered. In addition to the
      well-known hazards of water borne infectious diseases associated with the use of
      surface water, recently the potential public health implications of toxic
      cyanobacteria have been recognized. As a first step towards a risk assessment for
      cyanotoxins in Bangladesh surface waters, seston samples of 79 ponds were
      analysed in late summer 2002 for the presence of cyanobacteria and microcystins
      (MCYST), the most frequently detected cyanobacterial toxins worldwide.
      Microcystins could be detected in 39 ponds, mostly together with varying
      abundance of potentially microcystin-producing genera such as Microcystis,
      Planktothrix and Anabaena. Total microcystin concentrations ranged between <0.1
      and > 1,000 microg l(-1), and more than half of the positive samples contained
      high concentrations of more than 10 microg l(-1). The results clearly show that
      concentrations of microcystins well above the provisional WHO guideline value of
      1 microg l(-1) MCYST-LR can be frequently detected in Bangladesh ponds. Thus, an
      increasing use of surface water for human consumption introduces a risk of
      replacing one health hazard by another and therefore needs to be accompanied by
      cyanotoxin hazard assessments.

PMID- 16459840
TI  - The adsorption of cyanobacterial hepatoxins as a function of soil properties.
AB  - Cyanobacterial hepatotoxins present a risk to public health when present in
      drinking water supplies. Existing removal strategies, although efficient, are not
      economically viable or practical for remote Australian communities and developing
      nations. Bank filtration is a natural process and a potential low cost, toxin
      removal strategy. Batch studies were conducted in 12 texturally diverse soils to
      examine the soil properties influencing the adsorption of the cyanobacterial
      hepatotoxins, microcystin-LR and nodularin. Sorption isotherms were measured.
      Freundlich and linear isotherms were observed for both toxins with adsorption
      coefficients not exceeding 2.751 kg(-1) for nodularin and 3.81 kg(-1) for
      microcystin. Significant positive correlations were identified between
      hepatotoxin sorption and clay and silt contents of the soils. Desorption of
      toxins was also measured in three different soils. Pure nodularin and microcystin
      LR readily desorbed from all soils.

PMID- 16459841
TI  - Spatial and rainfall related patterns of bacterial contamination in Sydney
      Harbour estuary.
AB  - Water quality in recreational areas in Sydney Harbour, Australia, was analysed
      first to identify spatial patterns in faecal coliform and enterococci densities,
      and then to determine the relationship between bacterial densities and catchment
      rainfall. Non-metric multidimensional scaling separated sites closest to the
      mouth of the harbour from those further up the harbour's west and north-west
      arms. Sites closest to the harbour mouth generally had lower frequencies of high
      bacterial densities that exceeded median water quality guideline values. We
      attribute this to greater tidal flushing at sites closer to the harbour mouth.
      Eight site groups were identified within the harbour. Within each group, multiple
      regression analyses indicated rainfall accounted for between 15 and 66% of the
      variability in the bacterial densities. Variation in bacterial densities
      explained by rainfall was lower for sites closer to the harbour mouth where tidal
      flushing is greatest. Thus, our findings indicate that simple rainfall-based
      regression models are appropriate for predicting bacterial concentrations when
      flushing at a site is limited. More complex models incorporating a suite of
      environmental variables may improve the ability to predict bacterial
      concentrations at well-flushed sites, but even then, their predictive ability may
      be low.

PMID- 16459842
TI  - Effect of disinfectants on microbial ecology in model distribution systems.
AB  - This research was conducted to assess the impact of various disinfectants on
      bacterial water quality within model distribution systems (i.e. annular
      reactors). After colonization with non-disinfected water, annular reactors were
      treated with relatively low doses of chlorine (0.4 mg/l), chlorine dioxide (0.15
      mg/l), or chloramines (0.9 mg/l). Under the tested conditions, bacterial
      inactivation varied as a function of disinfectant type (ranking by efficiency per
      mg of oxidant: ClO2 > Cl2 > ClNH2) and sample type (bulk water vs. biofilm).
      Depending on the disinfectant, the log inactivation of suspended and attached
      bacteria were 0.7-1.2 and 0.5-1.0, respectively. The characterization of
      microbial communities in drinking water can be performed using biochemical and/or
      molecular methods. In this study, biochemical tests were used, showing that
      pseudomonad and pseudomonad-like bacteria, as in other studies, were the most
      predominant micro-organisms (e.g. Pseudomonas fluorescens, Brevundimonas
      vescularis). The ratio Gram-positive to Gram-negative organisms was 1 to 3. No
      drastic differences were observed between the non-treated and disinfected pipes.
      Based on the bacteriological data presented in these experiments, chlorine
      dioxide represents an alternative to chlorine for certain distribution systems.

PMID- 16459843
TI  - Evaluation of microbiological quality of coastal waters in Greece.
AB  - To evaluate the microbiological water quality of bathing sites along the Achaia
      coastline (south western Greece), a survey was conducted to determine the
      concentration of faecal bacterial and phage indicators as well as the presence of
      human viruses. Seawater samples (234) were collected from nine bathing sites on
      the Achaia coastline and were analysed for the presence of: total coliforms,
      faecal coliforms, faecal streptococci, Escherichia coli, somatic coliphages, F
      RNA bacteriophages, bacteriophages infecting Bacteroides fragilis, enteroviruses,
      adenoviruses and hepatitis A viruses. Most of the bacteriological analysis
      results were in accordance with the European Union standards. In all sites,
      bacteriophages were detected occasionally. Enteroviruses and adenoviruses were
      detected in 24 samples (10.26%) and 37 samples (15.81%) respectively. No samples
      were positive for the presence of hepatitis A virus. The overall data indicates
      that bathing sites are impacted by human faecal material. Both bacterial
      indicators and phages have low predictive capability for the presence of human
      viruses in coastal waters. None of the environmental parameters analysed was
      strongly related to the presence of the indicator organisms and viruses.
      Appropriate and effective administrative measures that should be taken into
      account may be considered in order to improve water quality and reduce public
      health risk.

PMID- 16459844
TI  - A review of technologies for rapid detection of bacteria in recreational waters.
AB  - Monitoring of recreational beaches for fecal indicator bacteria is currently
      performed using culture-based technology that can require more than a day for
      laboratory analysis, during which time swimmers are at risk. Here we review new
      methods that have the potential to reduce the measurement period to less than an
      hour. These methods generally involve two steps. The first is target capture, in
      which the microbial group of interest (or some molecular/chemical/or biochemical
      signature of the group) is removed, tagged or amplified to differentiate it from
      the remaining material in the sample. We discuss three classes of capture
      methods: 1) Surface and whole-cell recognition methods, including immunoassay
      techniques and molecule-specific probes; 2) Nucleic acid methods, including
      polymerase chain reaction (PCR), quantitative PCR (Q-PCR), nucleic acid sequence
      based amplification (NASBA) and microarrays; and 3) Enzyme/substrate methods
      utilizing chromogenic or fluorogenic substrates. The second step is detection, in
      which optical, electrochemical or piezoelectric technologies are used to quantify
      the captured, tagged or amplified material. The biggest technological hurdle for
      all of these methods is sensitivity, as EPA's recommended bathing water standard
      is less than one cell per ml and most detection technologies measure sample
      volumes less than 1 ml. This challenge is being overcome through addition of
      preconcentration or enrichment steps, which have the potential to boost
      sensitivity without the need to develop new detector technology. The second
      hurdle is demonstrating a relationship to health risk, since most new methods are
      based on measuring cell structure without assessing viability and may not relate
      to current water quality standards that were developed in epidemiology studies
      using culture-based methods. Enzyme/substrate methods may be the first rapid
      methods adopted because they are based on the same capture technology as
      currently-approved EPA methods and their relationship to health risk can be
      established by demonstrating equivalency to existing procedures. Demonstration of
      equivalency may also be possible for some surface and whole-cell recognition
      methods that capture bacteria in a potentially viable state. Nucleic acid
      technologies are the most versatile, but measure nonviable structure and will
      require inclusion in epidemiological studies to link their measurement with
      health risk.

PMID- 16459845
TI  - A methodology for the evaluation of disinfection technologies.
AB  - There are several concerns associated with the use of chlorine for potable water
      disinfection. These are the resistance of certain pathogens, the formation of
      toxic disinfection by-products and the adverse effects on aesthetic water
      quality. Owing to these concerns the water industry is continually reviewing
      alternative disinfection technologies. A methodology has been devised that will
      aid the water industry in evaluating the potential of these technologies. The
      methodology uses seven criteria to evaluate the technologies, these are:
      inactivation efficiency, disinfection byproduct (DBP) formation, toxicity,
      aesthetic water quality, cost, scalability and residual maintenance. Each
      criterion is assessed by associated questions in order of importance in
      accordance with a protocol. The criteria are evaluated using UK water quality
      regulations as standards. Ultraviolet (UV) disinfection was used as an example to
      demonstrate the methodology. UV was shown to meet all the criteria apart from the
      provision of a residual disinfectant. Several other disinfection technologies
      were evaluated using the methodology. Direct electrochemical disinfection and
      mixed oxidant generators were identified as having the most potential for
      replacing chlorination.

PMID- 16459846
TI  - Detection of Helicobacter pylori and fecal indicator bacteria in five North
      American rivers.
AB  - This study examines the use of fecal indicator bacteria (FIB) as a predictor of
      the presence of Helicobacter spp. A combination of standard culture and molecular
      techniques were used to detect and quantify FIB, Helicobacter spp. and H. pylori
      from five North American rivers of different size and with different land use
      characteristics. Primers designed to amplify genes specific to Helicobacter spp.
      and H. pylori were evaluated for their efficacy in detection and quantification
      in environmental samples. Helicobacter spp. were detected in 18/33 (55%) of river
      samples. H. pylori was detected in 11/33 (33%) of river samples. FIB were found
      in 32/33 (96%) of river samples. When FIB abundance exceeded USEPA water quality
      standards for single samples, Helicobacter or H. pylori were detected in 7/15
      (47%) cases. No numerical correlation was found between the presence of FIB and
      either Helicobacter spp. or H. pylori. This suggests that the presence of FIB
      will be of limited use for detection of Helicobacter spp. or H. pylori by public
      health agencies.

PMID- 16459847
TI  - Comparison of disinfectants for biofilm, protozoa and Legionella control.
AB  - The aim of this study was to compare the efficiency of different disinfectants
      applicable to Legionella control in domestic water systems. A domestic water
      supply simulation unit that allowed simulation of real-world conditions was
      developed for this purpose. The system, consisting of seven identical rigs, was
      used to compare treatment efficiency under equivalent conditions of system
      design, materials, hydraulics, water quality, temperature and initial
      contamination. During the study, each of six loops received continuous
      application of one of the following disinfectants: chlorine, electro
      chlorination, chlorine dioxide, monochloramine, ozone, or copper/silver. The
      seventh loop was used as a control and remained untreated. Performance evaluation
      of these disinfectants was based on their ability to reduce not only Legionella,
      but also protozoa and biofilms, which contribute to the establishment and
      dissemination of these bacteria in water systems, and their resistance to
      treatments. Regarding these criteria, chlorine dioxide and chlorine (as bleach or
      obtained by electro-chlorination) were the most effective treatments in this
      study. However, in comparison with chlorine, chlorine dioxide showed a longer
      residual activity in the system, which constituted an advantage in the
      perspective of an application to extensive pipework systems.

PMID- 16459849
TI  - Quantifying the impact of runoff events on microbiological contaminant
      concentrations entering surface drinking source waters.
AB  - Concentrations of microbiological contaminants in streams increase during
      rainfall-induced higher flow 'event' periods as compared to 'baseflow'
      conditions. If the stream feeds a drinking water reservoir, such periods of
      heightened pathogen loads may pose a challenge to the water treatment plant and
      subsequently a health concern to water consumers downstream. In order to manage
      this risk, it is desirable to first quantify the differences in surface water
      quality between baseflow and event conditions. The Event Mean Concentration (EMC)
      is a flow-weighted average concentration of a contaminant over the duration of a
      single event, proposed here as a standard parameter for quantifying the net
      effect of events on microbial water quality. Application of the EMC concept was
      assessed using flow and quality data for several events from an urbanised
      catchment. Expected mean EMCs were significantly larger than expected mean
      baseflow concentrations (p-value< or =0.012) for three microbial agents -
      Escherichia coil (13,000 [n = 7] v. 610 [n = 16] mpn/100 ml), Cryptosporidium
      (234 [n = 6] v. 51 [n = 16] oocysts/10 litres) and Campylobacter (48 [n = 5] v.
      2.1 [n = 16] mpn/100ml). These parameter estimates were complemented by
      estimating data variability and uncertainty in the form of second-order random
      variables. As such the results are in a format appropriate for potential use as
      components in probabilistic risk assessments evaluating the effect runoff events
      have on drinking water quality.

PMID- 16459850
TI  - Effects of weather and river flow on cryptosporidiosis.
AB  - Outbreaks of cryptosporidiosis have been linked to weather patterns such as heavy
      precipitation. However, outbreaks only account for a small percentage of all
      cryptosporidiosis cases and so the causes of the majority of cases are uncertain.
      This study assessed the role of environmental factors in all cases of
      cryptosporidiosis by using ordinary least-squares regression to examine the
      relationship between the monthly cryptosporidiosis rate, and the weather and
      river flows in England and Wales between 1989 and 1996. Between April and July
      the cryptosporidiosis rate was positively related to maximum river flow in the
      current month. Between August and November cryptosporidiosis was also positively
      linked to maximum river flows in the current month but only after accounting for
      the previous month's temperature, precipitation and monthly cryptosporidiosis
      rate. No associations were found between December and March. Through an
      understanding of the environmental processes at work, these relationships are all
      consistent with an animal to human transmission pathway especially as the
      relationships vary throughout the year. This study therefore indicates the
      importance of an animal to human transmission pathway for all cases of
      cryptosporidiosis.

PMID- 16459848
TI  - The background state leading to arsenic contamination of Bengal basin
      groundwater.
AB  - The Bengal basin has the world's densest water diversion constructions on the
      natural courses of rivers. The most damaging water diversion construction is the
      Farakka Barrage upon the international River Ganges. The diversion of water
      through this barrage and other constructions upstream of it has reduced the
      Ganges flow rate by 2.5 times. The resulting downstream effects are the depletion
      of surface water resources, more withdrawal than recharge of groundwater, sinking
      groundwater table, spread in depth and extension of the vadose zone, changes in
      surface features, climatic changes, etc. An investigation was carried out to find
      the contributions of water diversion to the arsenic contamination of groundwater
      in the Bengal basin. The reasonable scenario for arsenic contamination is the
      oxygen deficiency in groundwater and aeration of arsenopyrites buried in the
      sediment that would remain under water prior to 1975. The mineral forms water
      soluble compounds of arsenic when react with atmospheric oxygen. These soluble
      arsenic compounds infiltrates to the groundwater. This article summarizes the
      short-time and incomplete study-based quick conclusions reached by investigators
      that have totally avoided the vital issue of water diversion. It then shows the
      depleting condition of the water resources under continuing diversions, the
      generation of favorable condition for arsenic release, the reasons for low sulfur
      concentration, the reason for first contamination in the Hugly basin, and the
      hindrance to water's self-purification. The articles advocates that the
      restoration of the virgin wetland ecosystems in the Bengal basin following the
      stoppage of the inordinate amount of unilateral upstream water withdrawals can
      remove the catastrophe.

PMID- 16459851
TI  - Tourniquet injuries: pathogenesis and modalities for attenuation.
AB  - Although it is widespread in orthopaedic surgery, tourniquet use is associated
      with appreciable morbidity and even mortality. We review the use of tourniquets,
      highlighting how an understanding of their design and application can reduce the
      complications and injuries associated with their use. We also review the attempts
      being made to modulate these injuries through physical and pharmacological
      advances, in particular looking at the phenomenon of preconditioning.

PMID- 16459852
TI  - Morton's metatarsalgia: pathogenesis, aetiology and current management.
AB  - The aetiology and pathogenesis of Morton's Neuroma remain controversial. It is
      not true neuroma and therefore, it is better referred to as Morton's
      metatarsalgia. This article reviews the various thoughts regarding the
      pathogenesis of this condition. Chronic trauma, ischaemia, bursitis and
      entrapment neuropathy have been proposed as possible aetiologic factors. Careful
      history and clinical examination is essential to establish the diagnosis.
      However, if the clinical picture is doubtful, radiological investigation is
      recommended. Ultrasound, in the hand of an experienced radiologist, is the
      modality of choice. Conservative measures such as footwear modification and
      targeted injection of the hot spot are attempted before considering surgical
      intervention. Patients must be counselled preoperatively. The success of
      neurectomy rarely exceeds 83%. When surgery is considered, the dorsal approach is
      associated with less wound complications than the plantar approach. The neuroma
      is resected as proximally as possible in order to include plantar digital
      branches. For recurrent neuromas, a plantar approach is appropriate.

PMID- 16459853
TI  - The short term effects of a single corticosteroid injection on the range of
      motion of the shoulder in patients with isolated acromioclavicular joint
      arthropathy.
AB  - This study is aimed at evaluating the short-term effects of a single
      corticosteroid injection of the acromioclavicular joint on the range of motion of
      the shoulder joint using a three dimensional electromagnetic tracking system
      (FASTRAK) in patients with isolated unilateral acromioclavicular joint (ACJ)
      arthropathy. Eighteen patients (16 male, 2 female; mean age: 47.53 years), with
      isolated unilateral ACJ arthropathy were included in the study. Injection of the
      symptomatic ACJ with local anaesthetic and corticosteroid was performed under
      image intensifier guidance. Bilateral shoulder FASTRAK assessment before and two
      weeks after injection of the symptomatic ACJ was performed, measuring
      flexion/extension, anatomical abduction, scapular abduction and horizontal cross
      body adduction. Pain was measured using a visual analogue scale. There was a
      significant difference in the range of movement between the symptomatic and
      asymptomatic shoulder before the injection (p < 0.01). Range of extension and
      pain score of the symptomatic shoulder improved significantly (p < 0.05 and p <
      0.001, respectively) after the injection. In patients with radiographical
      evidence of degenerative ACJ disease, there was also significant improvement in
      the range of horizontal flexion (p < 0.05). Injection of the ACJ with local
      anaesthetic and corticosteroid was found to produce short-term pain relief and
      partial improvement in the range of movement. FASTRAK is useful in the
      measurement and documentation of range of motion, and can be used to assess the
      treatment outcome in patients with isolated ACJ arthropathy.

PMID- 16459854
TI  - Outcome of open rotator cuff repair. An analysis of risk factors.
AB  - The aim of this study was to evaluate the long-term functional outcome of full
      thickness rotator cuff tears treated by open repair and acromioplasty and to
      determine various factors affecting the outcome. This is a prospective clinical
      study on 42 patients who underwent full thickness rotator-cuff repair by a single
      surgeon between 2000 and 2003. The mean follow-up was 26 months. In patients with
      massive rotator cuff tear (n = 15), increase in the mean postoperative Constant
      score was significantly less compared to patients with small and moderate tears
      (p < 0.01). In patients older than sixty years, the improvement in postoperative
      Constant score was significantly less compared to the rest of the patients (p <
      0.001). However, the postoperative Constant score significantly improved from the
      preoperative score in all patient groups (p < 0.0001). There was a significant
      negative correlation with size of cuff tear, age of the patient and Constant
      Murley score (p < 0.05). Body mass index, smoking, gender, and the duration of
      symptoms did not have a significant effect on either Constant-Murley score or
      visual analogue score. We conclude that older patients and those with massive
      rotator cuff tear could benefit from surgical intervention, although not as much
      as younger patients and those with small/moderate size cuff tears.

PMID- 16459855
TI  - Treatment of irreparable rotator cuff tears by latissimus dorsi muscle transfer.
AB  - In this retrospective study, a latissimus dorsi transfer as first described by
      Gerber in 1988 was performed in 12 patients with massive, irreparable rotator
      cuff tears. Their average age was 59 years and the preliminary results are
      reported here after an average follow-up of 39 months. In 50% of the patients
      there was no pain and 41% had mild to moderate pain at follow-up. Functional
      Constant scoring was excellent in 42%, good in 8%, moderate in 42% and poor in
      8%. Active range of motion in the shoulder improved significantly in external
      rotation and abduction. Abduction force as measured with Atlantech and Cybex
      systems showed weak results. In two patients these tests could not be performed
      due to lack of force, in 9 patients abduction force was much weaker than on the
      contralateral side and in one patient the operated arm was stronger than the
      other side. We conclude that in most patients good pain relief and functional
      improvement can be achieved after latissimus dorsi transfer for irreparable
      rotator cuff tear. A good active range of motion can be expected but a lack of
      force persists. However, it remains difficult to conclude for which patients this
      surgery can be predictably successful.

PMID- 16459856
TI  - Complications and functional outcome following fixation of complex, intra
      articular fractures of the distal radius with the AO Pi-Plate.
AB  - This study investigates the efficacy of the AO Pi-plate in the treatment of
      complex, intra-articular fractures of the distal radius. We retrospectively
      analysed the clinical and radiological results of 19 consecutive patients who
      underwent open reduction and internal fixation for dorsally displaced, intra
      articular fractures of the distal radius using the AO Pi-plate. The final
      functional outcome was assessed using the Gartland & Werley scoring system. The
      average follow-up period was 34.3 months. Wrist movement was restored to a near
      normal range in all the patients. The functional outcome as measured by the
      Gartland & Werley scoring system showed excellent and good results in 15 (88%) of
      the patients. The implant was removed in 4 (23%) of the patients due to extensor
      tenosynovitis and restriction of flexion. This study demonstrates that although
      the functional outcome following fixation of complex distal radius fractures with
      the AO Pi-plate is good, there is a risk of developing extensor tenosynovitis and
      limitation of flexion. We recommend that the implant be used sparingly and if
      used then elective removal of the implant should be considered after fracture
      union.

PMID- 16459857
TI  - The surgical treatment of developmental dislocation of the hip in older children:
      a comparative study.
AB  - The aim of this retrospective study was to compare simultaneous open reduction
      and Salter innominate osteotomy versus one-stage combined surgical treatment
      including femoral shortening. A total of 24 patients were studied. Group 1
      included 16 hips in 14 patients treated by simultaneous open reduction and Salter
      innominate osteotomy; Group 2 included 13 hips in 10 patients treated by one
      stage open reduction, Salter innominate osteotomy and femoral shortening. The
      average age at the time of operation was 4.1 years (range: 3.3 to 5.1). Average
      follow-up was 5.3 years (range: 2.7 to 9.0). Clinical and radiological assessment
      at final follow-up showed that the outcome was not significantly different
      between the two groups. The duration of operation, however, was significant
      different between the groups. Patients with DDH between 3 and 5 years of age were
      treated successfully with either simultaneous open reduction and Salter
      innominate osteotomy or a one-stage combined surgical procedure including femoral
      shortening. Clinical and radiological outcomes were similar. Nevertheless, after
      this follow-up period, the rate of avascular necrosis was slightly higher in
      Group 1; on the other hand, one-stage combined surgical treatment including
      femoral shortening significantly prolonged the operative time.

PMID- 16459858
TI  - Outcome of pelvic support osteotomy with the Ilizarov method in the treatment of
      the unstable hip joint.
AB  - Instability of the hip joint in the young adult is a difficult problem. Patients
      with an unstable hip secondary to any aetiology usually have loss of bone from
      the proximal femur or shortening of the limb or both. In this study we report our
      results in the treatment of the unstable hip joint in young adults by pelvic
      support osteotomy using the Ilizarov method. From 1997 to 2004, 25 patients (17
      females and 8 males) with an unstable hip joint were treated in the Orthopaedic
      department of Mansoura University Hospital, Egypt. Their mean age was 22.4 years
      (range: 19 to 35). The main complaints were pain, leg length discrepancy,
      limping, and limited abduction of the hip. All patients underwent valgus
      extension osteotomy in the proximal femur and distal femoral osteotomy for
      lengthening. The average follow-up ranged from 2 to 7 years. All hips were pain
      free at follow-up. The Trendelenburg sign became negative in 20 patients. There
      was no limb length discrepancy and alignments of the extremity were re
      established. Five patients had a lurch gait. Valgus extension osteotomy has
      provided stability of the hip joint and maintained some motion of the hip joint.
      By using the Ilizarov technique, we could prevent the valgus effects created by
      the valgus extension osteotomy while achieving lengthening of the femur through
      the distal osteotomy in the femur.

PMID- 16459859
TI  - Early repetitive radiography is unnecessary after an uncomplicated cemented hip
      or knee arthroplasty for osteoarthritis.
AB  - Radiographs are necessary at some early point after a hip and knee arthroplasty.
      The aim of this study was to assess the value of routine repetitive radiographic
      examinations and the value of a reading of the images by a radiologist. Data of
      200 cemented hip and knee arthroplasties for osteoarthritis were reviewed. In
      hospital and outpatient postoperative control radiographs were examined. If post
      operative radiographs are of good quality, there seems to be no need for early
      repetitive radiographs. Neither is a radiologist reading of the radiographs after
      joint arthroplasty of any benefit.

PMID- 16459860
TI  - Computer-assisted total knee arthroplasty: comparative results in a preliminary
      series of 72 cases.
AB  - The aim of this study was to assess the value of navigation in achieving correct
      positioning of the implants and soft-tissue balance in total knee arthroplasty.
      We compared the axis alignment achieved in 72 LCS TKA's performed with navigation
      assistance to a historical cohort of 62 LCS TKA's implanted with the conventional
      instrumentation. The position of the tibial and femoral implants and the post
      operative mechanical axes of the lower limbs were compared in the two series:
      there was a highly significant improvement in the alignment accuracy in the
      navigated series (p < 0.0001). There were no outliers in the computer-assisted
      series whereas 47% of the cases in the conventional series showed deviations of
      the mechanical axis of the lower limb of more than 2 degrees from neutral
      alignment. However, the position of the femoral implants in rotation was not
      improved, suggesting that there may be a need for a more refined technique for
      rotational alignment of the femur, which was based essentially in the present
      series on ligament balance in flexion. The height of the joint line was preserved
      in 89% of the cases, validating the empirical use of the spreader tool prototype
      used during the study. Navigation eases optimal ligament balancing, by providing
      information that is used for appropriate release of soft tissue to achieve the
      proper mechanical axis. No major complication related to the use of navigation
      was observed. Operation time was lengthened on average by 30 minutes. Long-term
      studies are necessary to show whether better accuracy in ligament balancing and
      higher precision in restoration of mechanical axes will improve the functional
      results and the survival rate of knee arthroplasty.

PMID- 16459861
TI  - Computer-assisted technique versus intramedullary and extramedullary alignment
      systems in total knee replacement: a radiological comparison.
AB  - Malalignment in total knee replacement (TKR) is frequently associated with
      earlier failure and poor functional results. The authors compare the radiological
      results achieved in three consecutive series of TKRs using a computer-based
      alignment system (38 cases), a totally intramedullary alignment system (40 cases)
      and a totally extramedullary alignment system (37 cases). The frontal-femoral
      component angle (FFC), the frontal-tibial-component angle (FTC), the hip-knee
      ankle angle (HKA) and the sagittal orientation of the tibial component (slope)
      were evaluated 12 months after operation. The results did not show any
      statistically significant differences between the mean values of FFC, FTC, HKA
      angles and tibial slope among the three groups. However in the extramedullary
      alignment group there was a statistically higher percentage of TKRs with abnormal
      FFC and HKA angles. Furthermore all the implants in the computer aligned group
      were aligned within 4 degrees both of an ideal HKA and tibial slope.

PMID- 16459862
TI  - Total knee arthroplasty with conventional or navigated technique: comparison of
      the learning curves in a community hospital.
AB  - We performed a comparative study of the short-term radiological and clinical
      results after implantation of an unconstrained TKA with preservation of the
      posterior cruciate ligament with a conventional (50 cases--group A) or navigated
      (50 cases--group B) technique. The primary criterion was the postoperative leg
      coronal alignment measured on 3-month postoperative anteroposterior long-leg
      radiographs by the HKA angle: the expected alignment was 180 degrees +/- 3
      degrees. The mean post-operative HKA angle was 180 degrees +/- 3 degrees in group
      A and 180 degrees +/- 1 degrees in group B (p = 0.15). Thirty-four cases in group
      A and all 50 cases in group B were in the desired range (p < 0.001). The
      navigated system used in this study allowed for a significantly better alignment
      accuracy than the conventional implantation technique. Acceptable routine
      implantation was achieved during the time of the study (first 50 cases). We can
      thus hypothesise that the learning curve of the navigated technique used is not
      any longer than the learning curve of a conventional implantation technique.

PMID- 16459863
TI  - Hoffa's fat pad resection in total knee arthroplasty.
AB  - The authors have studied the consequences of resection of Hoffa's fat pad during
      total knee arthroplasty (TKA). Sixty eight patients undergoing primary TKA were
      randomised to have Hoffa's fat pad either resected or preserved. Biopsy specimens
      of Hoffa's fat pad were taken for pathological study in all patients.
      Radiological, functional and clinical evaluation was made after surgery, before
      discharge from hospital, after one month and after six months. Thirty six percent
      of the patients were found to present inflammatory infiltration of Hoffa's fat
      pad, and severe fibrosis was found in 33 %. A progressive decrease in
      postoperative anterior knee pain was found in 95% of the patients in both groups.
      Hoffa's fat pad resection did not appear to result in a change in patellar tendon
      length during the first six months after TKA. Preoperative fibrosis of Hoffa's
      fat pad may play a role in postoperative pain and range of motion.

PMID- 16459864
TI  - Physician and patient based outcomes following surgical resection of Haglund's
      deformity.
AB  - Calcaneal ostectomy is the benchmark for definitive surgical treatment in
      patients with Haglund's syndrome, despite conflicting and unpredictable study
      results. The current study's hypothesis is that when adequate bone is resected
      and outcomes are evaluated using validated scores, calcaneal ostectomy can give
      reliable and predictable results. Thirty six consecutive patients (39 feet)
      underwent calcaneal ostectomy for Haglund's deformity between 1998 and 2002. All
      patients were evaluated with the AOFAS score and SF-36v2 questionnaire. The mean
      time to follow-up was 51 months. The mean AOFAS score following surgery was
      86/100 points; the mean SF-36v2 score following surgery was 144/152. Six of the
      36 patients interviewed, however, would not recommend the procedure to others,
      citing mainly prolonged recovery time. Calcaneal ostectomy achieves good-to
      excellent results in the treatment of Haglund's deformity when appropriate
      amounts of bone are excised. However, patients must be made aware of the
      necessary time to recovery, between 6 months and 2 years.

PMID- 16459865
TI  - Sciatic nerve block causing heel ulcer after total knee replacement in 36
      patients.
AB  - Femoral and sciatic nerve blocks are often used for postoperative analgesia
      following total knee replacement surgery. In this report, we focus on cases of
      heel ulcers which occurred following the implementation of peripheral nerve block
      in concert with knee replacement surgery. In some instances, heel ulcers have
      resulted in delayed rehabilitation and prolonged hospital stays in this group of
      patients, which makes this phenomenon a potential burden on the healthcare
      system. Pressure points in the foot should be protected after the implementation
      of nerve blocks to prevent pressure sores. An awareness of this unusual
      complication related to knee replacement surgery is necessary to prevent its
      occurrence and avoid delays in patient rehabilitation and recovery.

PMID- 16459866
TI  - Radiological analysis of titanium mesh cages used after corpectomy in the
      thoracic and lumbar spine: minimum 3 years' follow-up.
AB  - This study analyses radiological outcome of titanium mesh cages used for anterior
      column support following corpectomy in the thoracic and lumbar spine in 34
      patients with a minimum three-year follow-up. The aim of the study was to assess
      the complications and radiological outcomes of patients with structural cages
      implanted into the anterior column. Titanium mesh cages for the anterior column
      became popular for anterior column reconstruction following discectomy and
      corpectomy. Few clinical studies are published assessing their efficacy as a
      structural graft after corpectomy and factors for the development of settling and
      correction loss are not investigated enough. Thirty-four patients with minimum 3
      year follow-up were analysed radiologically for correction achievement, cage
      settling and fusion inside the mesh cage. The effect of fixation technique,
      anatomical localisation and diagnosis for the development of settling were
      analysed. Measurements of preoperative and early postoperative local kyphotic
      angle revealed that a mean correction of 27 degrees (range: 8 to 60) was
      obtained. While no dislodgement or fracture of titanium mesh cages was observed,
      there was a mean correction loss of 4 degrees and settling (> 2 mm) was noted in
      6 patients. Short posterior and only anterior instrumentation systems were
      associated with settling. The anatomical location and diagnosis did not affect
      the development of cage settling. Following corpectomy and mesh cage
      implantation, isolated anterior fixation or short posterior fixation do not
      provide enough stability, and correction loss and settling can occur.

PMID- 16459867
TI  - Rotator cuff impingement due to enchondroma of the acromion.
AB  - We report the case of a patient with a long standing clinical history of
      subacromial impingement, in which plain radiographs and CT-scan revealed a well
      circumscribed lucent lesion expanding the undersurface of the acromion. MRI
      showed the subacromial fat to be completely obliterated and the infraspinatus
      tendon deformed due to compression by a mass localised at the acromion. The
      acromial lesion was curetted, and histopathologic analysis was consistent with
      the diagnosis of enchondroma. Tumours located in the coracoacromial arch have
      been very rarely reported as a cause of subacromial impingement. To the best of
      our knowledge, this is the first description of subacromial impingement secondary
      to acromial enchondroma.

PMID- 16459868
TI  - Osteoblastoma of the proximal ulna, an unusual cause of ulnar wrist pain. A case
      report.
AB  - During the diagnostic investigation of a patient with ulnar wrist pain, a hot
      spot in the proximal ulna was revealed on the technetium scintigram, which was
      found on radiographs to correspond to an osteolytic lesion in the proximal ulna.
      The lesion was resected and the histological diagnosis was an osteoblastoma. The
      wrist symptoms disappeared after resection of the lesion in the proximal ulna.

PMID- 16459869
TI  - Stress fracture of the acetabulum in a ballet dancer. A case report.
AB  - The authors report the case of a 26-year old professional ballet dancer with
      chronic dysmenorrhea and a Body Mass Index of 17, who presented with right hip
      pain related with a stress fracture of the acetabulum. Plain radiographs were
      unremarkable and the diagnosis was made with magnetic resonance imaging.
      Conservative treatment including partial weight bearing with crutches for six
      weeks resulted in immediate resolution of symptoms. The authors discuss the
      specific risk factors for stress fractures encountered in professional ballet
      dancers, such as hypogonadism and eating disorders.

PMID- 16459870
TI  - Rupture of adductor longus tendon due to ciprofloxacin.
AB  - We present a rare case of spontaneous rupture of the adductor longus tendon
      induced by ciprofloxacin. A 35-year-old man was diagnosed with pneumonia and was
      recommended ciprofloxacin 500 mg iv twice a day for 7 days. Three days after
      receiving the initial dose, he developed discomfort in his left medial thigh, and
      pain and swelling in the same area followed ten days later. He consulted us when
      he noted a palpable mass on the medial side of his left thigh, and MRI study
      revealed adductor longus tendon rupture. There was no obvious underlying disease
      or other factor causing fragility of his adductor longus tendon. We review the
      pathophysiological mechanisms leading to fluoroquinolone-related tendon rupture
      as well as the risk factors and discuss proper management.

PMID- 16459871
TI  - Occult ligamentous injury of the cervical spine associated with cervical spine
      fracture.
AB  - We report the case of a 20-year-old patient with a C5 cervical spine fracture and
      an undetected ligamentous lesion between C1 and C2. Cervical spine lesion
      protocols and the rates of lesions that are not diagnosed with standard
      evaluation protocols are reviewed, with particular emphasis on comatose patients.
      Dynamic studies during the surgical procedure for fixation of the fracture are
      recommended to increase the detection of ligamentous lesions.

PMID- 16459872
TI  - High-grade dysplastic spondylolisthesis and spondyloptosis: report of three cases
      with surgical treatment and review of the literature.
AB  - High-grade dysplastic spondylolisthesis is extremely rare and always involves the
      L5-S1 level. It is attributed to congenital dysplasia of the superior articular
      process of the sacrum. It can remain asymptomatic for a long time and can
      progress to a more severe grade of olisthesis and spondyloptosis. Surgical
      treatment has varied from posterior-only in situ fusion to anterior and posterior
      fusion with complete reduction. Three cases of symptomatic high-grade (4th and
      5th grade) dysplastic spondylolisthesis treated surgically with reduction and
      fusion are presented. Interbody fusion at the level of olisthesis is crucial.

PMID- 16459873
TI  - [AIDS still exists. Prevention!].

PMID- 16459874
TI  - [Drugs, a current problem: difficulties in handling drug addictions].
AB  - A patient suffering a drug addiction usually presents some characteristic demands
      and necessities. A professional's attitude must be clear and firm, showing
      empathy and being an active listener offering assistance, but not expressing
      either rebuke or threats. The professional attending such a patient takes
      advantage of a consultation to motivate the patient to begin, or continue,
      treatment in a corresponding specialized center and will process the necessary
      paperwork to contact such a center.

PMID- 16459875
TI  - [Changes in the perceptions of qualitative research and investigation].
AB  - Qualitative research and investigation has proven to be fundamental in sanitary
      practice and brings to bear a body of knowledge which can not be provided by
      other methods; although classically it has been considered a less scientific
      method of research, this perception which has changed in recent years.

PMID- 16459876
TI  - [Kinesiology].
AB  - Kinesiology is a holistic and complete methodology. Having great applications in
      sub-clinical situations and to get rid of stress, kinesiology has proven to be of
      great help in pathological cases, given its possibility to activate innate health
      mechanisms and through its capacity to reduce stress. kinesiology is very
      effective, since it is applied by means of the interested person's own muscles
      and at the same moment when information professionals work with is received.
      Besides being excellent therapy, its corrective techniques, by themselves, can
      improve the energetic and psychic state of a patient, thereby optimizing the
      resources people have in any situation.

PMID- 16459877
TI  - [Therapeutic and preventive vaccine against HIV problems and the necessity to
      develop one].
AB  - The development of therapeutic and preventive vaccines would be an essential
      accomplishment needed to control the spread of HIV and is an absolute necessity
      in developing countries. The vaccines developed by Spanish groups in centers in
      our country are found to be among the most promising in the world. The upcoming
      work by the Spanish Group "RIS" on Therapeutic and Preventive Vaccines might
      place Spanish professionals in the front line in the international fight against
      AIDS.

PMID- 16459878
TI  - [Updating enteral feeding by catheter].
AB  - Intestinal nutrition can be administered orally or by means of a catheter; the
      latter method is the focus of this article. The authors' objective is to provide
      up-to-date information in a succinct manner about the enteral feeding technique.
      The authors hope health professionals know the advantages as well as the
      inconveniences of the latest intestinal nutrition advances regarding access ways
      and the means to administer these. Intestinal nutrition formulas will not be
      dealt with in this article. However, a health professional should know that there
      is a wide variety of diets available depending on the complexity of
      macronutrients included in a diet, the quantity of proteins in a mixture, and
      that these are designed, in addition to feeding, to treat the specific
      pathological process a patient suffers from, such as diabetes of cancer.

PMID- 16459879
TI  - [5.07 Monofilament: the use of this monofilament in outpatient offices by nurses
      in primary health care units].
AB  - A diabetic foot is the most important cause of disability and loss of life
      quality among diabetics. To inspect a diabetic's feet and to explore his/her
      protective sensibility capability with a 5.07 monofilament are efficient methods
      to detect the risk of lesions. The authors' objective was to discover if our
      Primary Health Care Unit utilizes this instrument; therefore, we carried out a
      poll among all the nurses in our unit. 79% of these nurses are aware of the 5.07
      monofilament; 62% have this monofilament available for their use; 55% stated they
      utilize it. The primary reasons to not use this monofilament are its
      unavailability and a lack of knowledge regarding it. Priority must be given to
      facilitate the availability of this instrument and to promote among nurses an
      understanding how to correctly utilize a 5.07 monofilament.

PMID- 16459880
TI  - [Therapeutic behavior of a hydrocolloid dressing. Its evolution in the treatment
      of acute and chronic dermal ulcers].
AB  - OBJECTIVE: Evaluate the behavior of a Sureskin II hydrocolloid dressing in the
      treatment of acute and chronic dermal ulcers in daily clinical practice. METHODS:
      By means of an observational, multi-centric, prospective, open study of a series
      of clinical cases on patients afflicted by acute and chronic ulcers. This study
      lasted through 20 dressing changes or until the ulcer was cured. During the
      initial visit, the characteristics of the lesion were evaluated; in continuation,
      the evolution of a lesion as dressings were changed was evaluated; and during the
      final visit, the professional team evaluated the final traits of the lesion along
      with the overall behavior of the dressing applied. RESULTS: This study evaluated
      1080 patients whose average age was 72.3 years. At the conclusion of this study
      the investigators noticed that the size of these ulcers had significantly reduced
      from the start to the end of treatment. Epithelization increased from 43.2 to
      71.9%. 98.3% of patients in this study considered this dressing brand easy to
      apply Seepage of exudation diminished from 31.77 to 14.6%. The presence of
      maceration, erythema and eczema also reduced from 29.2 to 12.5%, from 37.6 to
      13.1% and from 9.7 to 6.3% respectively. The symptoms of infection or
      inflammation dropped from 22.6 to 7.6%. Patients' complaints of pain when their
      dressings were changed dropped 29.4%. 90.7% of these patients stated this
      treatment alleviated their symptoms and allowed them to carry on their daily
      activities in a normal fashion. CONCLUSION: The results of this study show that
      the use of Sureskin II is effective, therefore making it a first choice
      therapeutic option for treating patients suffering from acute and chronic dermal
      ulcers.

PMID- 16459881
TI  - [The family: the support for the elderly with cerebral-vascular accident].
AB  - This project had these objectives: 1) understand the reality of the family care
      system for an elderly person suffering from cerebral-vascular accident (CVA), 2)
      implement an aid to the family care system for an elderly person suffering from
      cerebral-vascular accident (CVA) from a holistic perspective on health. The
      sample for this investigation was composed by five families which were
      intentionally selected, with whom the authors shared the care of an elderly
      person suffering from CVA in their homes over a six month period. Based on
      concepts having a holistic reference about health formulated by Capra, the
      authors drew up the development of a methodology for research and action which
      has a participatory observation and a Drawing-Record procedural technique for the
      production of data. These data were subjected to a thematic analysis which made
      it possible to identify three main themes: 1) the main caretaker as the focus of
      the family care system; 2) the family care system as a context which has
      complexities and singularities, 3) the holistic nature of the family care system
      for an eldely person suffering from cerebral-vascular accident (CVA).

PMID- 16459882
TI  - Periodontal status and cytoplasmic enzyme activities in gingival crevicular fluid
      of type 2 diabetic and/or obese patients with chronic periodontitis.
AB  - Type 2 diabetes mellitus and obesity are the most common nutritional disorders in
      developed and developing countries. Increased prevalence of periodontal disease
      is a well-known complication of type 2 diabetes mellitus (DM). As obesity is
      generally the first step toward type 2 diabetes mellitus, it is possible to find
      exacerbated periodontal disease in obese patients, also. The purpose of this
      cross-sectional study was to investigate the periodontal status and aspartate
      aminotransferase and lactate dehydrogenase enzyme activities in gingival
      crevicular fluid (GCF) of type 2 diabetic and/or obese chronic periodontitis
      patients. A total of 39 chronic periodontitis patients participated in the study.
      The study population was divided into four groups according to body mass index
      and type 2 DM status: 1) type 2 DM obese patients, n = 8; 2) type 2 DM patients,
      n = 12; 3) obese patients, n = 8; 4) systemically healthy control group, n = 11.
      Enzyme activities in gingival crevicular fluid and periodontal status were
      evaluated. No significant differences in age, gingival index, plaque index,
      aspartate aminotransferase and lactate dehydrogenase enzyme activities were
      observed, but probing depths were significantly higher in the DM groups than in
      the control group. Obesity did not seem to be a significant factor in any
      parameters evaluated. The present study showed increased probing depth values for
      the diabetic groups but failed to show any significant relation between obesity
      and enzyme activity or periodontal status. However, the slightly increased
      probing depth values in the obese groups might be a clue to an impaired immune
      response and predisposition to periodontitis in that patient group.

PMID- 16459883
TI  - Clinical effectiveness and soft tissue compatibility of a temporary restorative
      material.
AB  - OBJECTIVE: The purpose of this six-week study was to evaluate in vivo the
      effectiveness of Systemp.inlay as a temporary restorative material. METHOD:
      Subjects with the proper indication for a class II restoration were entered into
      the study. Twenty-three subjects and twenty-nine temporary restorations were
      evaluated at time of placement, three and six weeks. Two faculty members were
      calibrated to evaluate the material. Following the six-week trial, the temporary
      restorative material was removed and the test teeth were restored with a
      definitive restorative material. RESULTS: The temporary restorative material
      provided mechanical and anticariogenic protection of tooth structure while
      preventing dental sensitivity and patient discomfort. It promoted soft tissue
      health as evidenced by the enhanced plaque and gingival indices found associated
      with the temporarily restored teeth. Its ease of placement and removal makes it
      an attractive alternative for the dental practitioner. The change in color of the
      material over the six-week duration of the study may limit its use to posterior
      teeth and to lingual/palatal surfaces of anterior teeth. CONCLUSION: Ease of
      placement and removal and retention of the temporary restorative material were
      extremely good. Marginal and surface integrity of the material was maintained and
      no or minimal sensitivity was reported throughout the study. The material did not
      promote the accumulation of plaque nor result in gingival inflammation. The color
      change noted was not of clinical importance. Therefore, this temporary
      restorative material was demonstrated to be clinically effective in Class II
      cavity preparations.

PMID- 16459884
TI  - Complex oral manifestations of an HIV-seropositive patient.
AB  - A complex manifestation of characteristic oral lesions occurring simultaneously
      in an HIV-seropositive patient is presented. Necrotizing ulcerative gingivitis
      (NUG), necrotizing ulcerative periodontitis (NUP), oral-facial herpes infection,
      pseudomembranous candidiasis and atypical oral ulceration are discussed. In spite
      of extremely low CD4+ T-cell counts of 3 x 10(6)/L and lack of anti-retroviral
      therapy, an AIDS patient responded favourably to standard periodontal therapy. In
      the follow-up period of 3 months, no recurrence of any of the oral lesions
      initially present occurred and no special prophylactic regimes were needed to
      maintain oral health. This case illustrates that appropriate management of the
      oral manifestations contributes significantly to improvement of the quality of
      life of patients in the terminal stage of HIV-AIDS.

PMID- 16459885
TI  - Sharpening of periodontal instruments with different sharpening stones and its
      influence upon root debridement--scanning electronic microscopy assessment.
AB  - The objective of this study was to evaluate, through scanning electronic
      microscopy, the effect of sharpening with different sharpening stones on the
      cutting angle of periodontal curettes (Gracey 5-6), and the influence on root
      surfaces after debridement and planing. The experimental model consisted of two
      different phases. In the first, the cutting angles of fifteen stainless steel
      Gracey 5-6 curettes were analyzed under a scanning electronic microscope after
      being sharpened with different types of stones. In the second phase, the root
      surfaces of 25 newly extracted teeth were evaluated with a scanning electronic
      microscope after being debrided with curettes sharpened with different stones.
      Analysis of the results showed that the synthetic stones (aluminum oxide and
      carborundum) are more abrasive and produce more irregular cutting angles, whereas
      Arkansas stones are less abrasive and produce smoother and more defined cutting
      angles. There was no significant statistical differences among the five groups
      tested with regard to the degree of irregularity of the root surfaces after
      instrumentation.

PMID- 16459886
TI  - Pleiotropism of bone morphogenetic proteins: from bone induction to
      cementogenesis and periodontal ligament regeneration.
AB  - Bone morphogenetic and osteogenic proteins (BMPs/OPs), pleiotropic members of the
      transforming growth factor-beta (TGF-beta) supergene family, induce de novo
      endochondral bone formation and act as soluble signals of tissue morphogenesis,
      sculpting the architecture of multicellular mineralized structures, including the
      periodontal tissues. The presence of multiple forms of BMPs/OPs has a therapeutic
      significance and the choice of a suitable protein will be a formidable challenge
      to the practising periodontologist. Amino acid sequence variations in the carboxy
      terminal domain, the molecular basis of the structure/activity profile of each
      isoform, confer specialized and pleiotropic activities to each morphogenetic
      protein. Naturally derived BMPs/OPs regenerate cementum and alveolar bone in
      mandibular furcation defects of the primate Papio ursinus. Tissue morphogenesis
      induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are
      applied singly, indicating that the structure/activity profile amongst BMPs/OPs
      is controlling pleiotropic tissue induction and morphogenesis. Furcation defects
      of Papio ursinus with root surfaces exposed long-term to periodontal pathogens
      and filled with granulation tissue after inoculation of a pathogenetic human
      strain of Porphyromonas gingivalis twice a month for 12 months were implanted
      with hOP-1 osteogenic devices. Six months after surgery there was regeneration of
      alveolar bone and induction of cementogenesis, with Sharpey's fibres uniting the
      regenerated bone to the newly formed cementum. Although within the natural milieu
      of the bone matrix a plurality of morphogens may be required to initiate the
      cascade of pattern formation and the attainment of tissue form and function,
      recombinant y-irradiated hOP-1 delivered by a xenogeneic collagenous matrix
      induces complete periodontal tissue regeneration on periodontally affected root
      surfaces, showing an additional specific function of hOP-1 for tissue
      morphogenesis in clinical contexts. The pleiotropy of the signalling molecules of
      the TGF-beta superfamily is additionally highlighted by the redundancy of
      molecular signals initiating endochondral bone induction by the TGF-beta isoforms
      per se, powerful inducers of endochondral bone, but in the primate only. A novel
      approach in periodontal tissue regeneration is to induce heterotopic bone to be
      transplanted as morcellised autogenous grafts into established periodontal
      defects. The induction of bone develops a mosaic structure in which the
      osteogenic proteins of the TGF-beta superfamily singly, synergistically and
      synchronously initiate and maintain tissue induction and morphogenesis, with
      specific roles at different time points of the morphogenetic cascade.

PMID- 16459887
TI  - Immunohistochemical localization of cytokeratin 19, involucrin and proliferating
      cell nuclear antigen (PCNA) in cultured human gingival epithelial sheets.
AB  - It has been suggested that human cultured gingival epithelial sheets may serve as
      a possible grafting material. The purpose of this study was to examine the
      biological characteristics of human cultured gingival epithelial sheets by
      epithelial differentiation and proliferation markers. Immunohistochemical
      localization of cytokeratin 19, involucrin and proliferating cell nuclear antigen
      (PCNA) were examined in human cultured gingival epithelial sheets samples from
      twenty patients. Cytokeratin 19-immunopositive cells were scattered mainly in the
      suprabasal layer. Immunoreactivity for involucrin was observed in all layers
      except for the basal layer. The majority of proliferating cell nuclear antigen
      immunopositive cells was found in the basal layer. These results suggested that
      the cultured human gingival epithelial sheets were biologically active and in
      proliferative condition, which implies that this biological product may be a
      potential grafting material.

PMID- 16459888
TI  - Obscure heroes.

PMID- 16459889
TI  - What does phenomenology offer to the study of care-giving?
AB  - Care giving to a dementia sufferer is complex (Parsons, 1997) and inherently
      stressful (Baldwin et al 1989). It is suggested that the predominance of the care
      giver stressor-burden research paradigm during the last thirty years has
      frequently been uni-dimensional, objectively oriented, generally equivocal, and
      unconvincing in its findings. Dillehay and Sandys (1990), suggest that
      preoccupation w ith such typically narrow approaches has delayed the much-needed
      development of a more accurate understanding of the lived experience (the
      phenomenology of care-giving). Researching the experience of care giving to a
      dementing relative requires a research strategy, which acknowledges the
      intricacies, complexities, subjectivity and humanness of that experience. That is
      the premise behind this paper. A multi-dimensional phenomenological PhD study is
      presented. The focus is on understanding care giving from the individual and
      collective perspectives of forty-six spouse caregivers. The methodological
      implications (including influences of Husserl and Heidegger) are outlined before
      the phenomenological research findings are presented and discussed. Ethical
      approval was given by the Bassetlaw Hospital and Community NHS Trust Ethics
      Committee (now part of the Nottinghamshire Healthcare NHS Trust).

PMID- 16459890
TI  - The influence of social support on caregiver coping.
AB  - Investigations into the act of proving care to a dementing family member
      typically approach the phenomenon from a stress/burden paradigm. Many studies
      have sought to highlight the relationship between of a range of dementia care
      factors (such as illness duration, patient symptoms/characteristics, service
      provision, etc.) and the experience of caregiver stress. Caregiving a spouse with
      dementing illness is complex and multidimensional (Gubrium, 1995) it is therefore
      not surprising that the vast majority of stressor-based approaches, though very
      revealing, have been largely equivocal in their findings. The relationship
      between the social support of family and friends and caregiver coping is no
      exception and therefore remains essentially unclear particularly in terms of its
      contribution in ameliorating stress (Thompson et al, 1993). Caregiver studies do
      however consistently highlight the pathogenic qualities of coping with an
      experience in which 'families are faced with often overwhelming and
      uncontrollable stress than can take a toll on their emotional health and well
      being' (Zarit et al, 1998; Bourgeois et al, 1996). This article, emanating from a
      PhD study into caregiver coping (Upton, 2001), illuminates the study of
      caregiving from a different perspective. It highlights and describes how
      phenomenological exploration deepens our understanding of how and why spouse
      caregivers cope and uses the influence of social support as an exemplar of the
      value and need for such exploration both for its own sake and also to inform
      service providers. The results revealed a universal phenomenon of psycho-physical
      distancing by family and friends affecting all forty-six spouse caregivers
      included in this study. The implications of these finding are discussed along
      with what constituted social support for these carers. Other phenomenological
      insights are revealed, not least how the individual caregiver's relationship to
      time, space and their own identity shaped their caregiving experiences.

PMID- 16459891
TI  - Research validation of misguided entitlement.
AB  - This writer theorized that psychiatric patients that exhibited high levels of
      "misguided entitlement" (ME) would share certain personality traits, including
      narcissism, aggression, sociopathy, paranoia, and depression. The Millon
      Multiaxial Clinical Inventory (MMCI-II) was the instrument chosen to measure
      these traits in a sample of 100 psychiatric hospital/day hospital patients
      (Millon, 1987). An Entitlement Scale (ES) was devised so that staff nurses could
      rate entitled behaviors observed in these same 100 patients during the daily
      course of providing care. Scores from both instruments then were tested for
      statistical significance. High ME (low scores) was found to be significantly
      correlated with high scores on Millon's aggression, sociopathy and paranoia
      scales, but were not with narcissistic or depressive personality patterns. These
      findings validated certain propositions put forth in the conceptual framework,
      and invalidated others (Kerr, 1985). Validity and reliability studies indicated
      that the ES was a valid and reliable instrument for measuring the behavioral
      manifestations of misguided entitlement.

PMID- 16459892
TI  - Cholesterol concentrations in patients with Anorexia Nervosa and in healthy
      controls.
AB  - Argentinean women have one of the highest international mortality rates for
      cardiovascular disease and they are particularly vulnerable to eating
      pathologies. Cardiovascular risk is exacerbated in women with Anorexia Nervosa
      (AN), since high cholesterol concentrations have been widely reported.
      OBJECTIVES: To compare blood cholesterol concentrations in AN patients with
      controls, and to correlate cholesterol with the body mass index (BMI), patient
      age, vomiting and tobacco. DESIGN AND METHOD: Cholesterol measurements documented
      at diagnosis from the clinical notes of patients were recorded from the
      Association Against Bulimia and Anorexia (ALUBA). Comparison was carried out with
      data of the general Argentinean public. RESULTS: Total cholesterol, LDL and HDL
      concentrations were higher in patients compared with controls. Total cholesterol
      in patients decreased during treatment and it was correlated with the patient
      age, but with no other variable. CONCLUSION: The abnormal lipid profile places
      patients at risk for cardiovascular disease. Older and untreated patients may be
      at particular higher risk of suffering from the consequences of elevated
      cholesterol concentrations.

PMID- 16459893
TI  - Word frequency effects in immediate serial recall of pure and mixed lists: tests
      of the associative link hypothesis.
AB  - In immediate serial recall, high-frequency words are better recalled than low
      frequency words. Recently, it has been suggested that high-frequency words are
      better recalled because of their better long-term associative links, and not
      because of the intrinsic properties of their long-term representations. In the
      experiment reported here, recall performance was compared for pure lists of high-
      and low-frequency words, and for mixed lists composed of either one low- and five
      high-frequency words or the reverse. The usual advantage of high-frequency words
      was found with pure lists and this advantage was reduced, but still significant
      with mixed lists composed of five low-frequency words. However, the low-frequency
      word included in a high-frequency list was recalled just as well as high
      frequency words. Results are challenging for the associative link hypothesis and
      are best interpreted within an item-based reconstruction hypothesis, along with a
      distinctiveness account.

PMID- 16459894
TI  - The implicit association test as a general measure of similarity.
AB  - The Implicit Association Test (IAT) is widely used as a measure of semantic
      similarity (i.e., associations in semantic memory). The results of previous
      research and of a new study show that IAT effects can, however, also be based on
      other types of similarity between stimuli. We therefore put forward the
      hypothesis that the IAT provides a general measure of similarity. Given that
      similarity is highly dynamic and context-dependent, our view that the IAT
      measures similarity is compatible with existing evidence showing that IAT effects
      are highly malleable. We provide further evidence for this in a new study in
      which the outcome of an IAT depended on whether the perceptual or functional
      characteristics of the stimuli were made salient.

PMID- 16459895
TI  - [The effect of deleting schwa (mute e) on spoken word recognition in French].
AB  - We studied the processing of two word strings in French made up of a determiner
      and a noun which contains a schwa (mute e). Depending on the noun, schwa deletion
      is present ("la tir'lire"), optional ("le ch(e)min") or absent ("la cornemuse").
      In a production study, we show that schwa deletion, and the category of the noun,
      have a large impact on the duration of the strings. We take this into account in
      two perception studies, which use word repetition and lexical decision, and which
      show that words in which the schwa has been deleted usually take longer to
      recognize than words that retain the schwa, but that this depends also on the
      category of the word. We explain these results by examining the influence of
      orthography. Based on the model proposed by Grainger and Ferrand (1996), which
      integrates the written dimension, we suggest that two sources of information,
      phonological and orthographic, interact during spoken word recognition.

PMID- 16459896
TI  - [Connection between the evaluation of positive or negative valence and verbal
      responses to a lexical decision making task].
AB  - Evaluation of the positive or negative valence of a stimulus is an activity that
      is part of any emotional experience that has been mostly studied using the
      affective priming paradigm. When the prime and the target have the same valence
      (e.g. positive prime and positive target), the target response is facilitated as
      a function of opposing valence conditions (e.g. negative prime and positive
      target). These studies show that this evaluation is automatic but depends on the
      nature of the task's implied response because the priming effects are only
      observed for positive responses, not for negative responses. This result was
      explained in automatic judgmental tendency model put forth by Abelson and
      Rosenberg (1958) and Klauer and Stern (1992). In this model, affective priming
      assumes there is an overlap between both responses, the first response taking
      precedence as a function of the prime-target valence, and the second response one
      that is required by the task. We are assuming that another type of response was
      not foreseen under this model. In fact, upon activating the valence for each of
      the prime-target elements, two preliminary responses would be activated before
      the response on the prime-target valence relationship. These responses are
      directly linked to the prime and target evaluation independently of the prime
      target relationship. This hypothesis can be linked to the larger hypothesis
      whereby the evaluative process is related to two distinct motivational systems
      corresponding to approach and avoidance behaviour responses (Lang, Bradley, &
      Cuthbert, 1990; Neuman & Strack, 2000; Cacciopo, Piester & Bernston, 1993). In
      this study, we use the hypothesis that when a word leads to a positive valence
      evaluation, this favours a positive verbal response and inversely, a negative
      valence word favours a negative response. We are testing this hypothesis outside
      the affective priming paradigm to study to what extent evaluating a word, even
      when it is not primed, activates both motivational systems and consequently,
      positive verbal responses for approach and negative responses for avoidance. To
      validate this hypothesis, we are re-using both versions of the lexical decision
      task proposed by Wentura (2000). The classic version leads participants to a
      positive response for words, and the modified version leads to a no response.
      This experiment, carried out with thirty-two participants, measures the influence
      on response time of two experimental factors, the intrasubject valence of words
      (positive and negative) and the inter-subject factor (yes and no responses to
      words). Results show an interaction between the type of response and word
      valence. It is temporally more onerous to give a no response to positive words
      than to negative words. This result confirms that there is a direct relation
      between the evaluation of a valence stimulus and the response to this stimulus, a
      relation that had up to now been essentially observed with motor behaviours, and
      more rarely with verbal responses. We propose integrating the existence of this
      link between evaluation and verbal response (yes and no) in interpreting the
      effects of affective priming.

PMID- 16459897
TI  - Arithmetic split effects reflect strategy selection: an adult age comparative
      study in addition comparison and verification tasks.
AB  - We tested whether split effects in arithmetic (i.e., better performance on large
      split problems, like 3 + 8 = 16, than on small-split problems, like 3 + 8 = 12)
      reflect decision processing or strategy selection. To achieve this end, we tested
      performance of younger and older adults, matched on arithmetic skills, on two
      arithmetic tasks: the addition/number comparison task (e.g., 4 + 8, 13; which
      item is the larger?) and in the inequality verification task (e.g., 4 + 8 < 13;
      Yes/No?). In both tasks, split between additions and proposed numbers were
      manipulated. We also manipulated the difficulty of the additions, which
      represents an index of arithmetic fact calculation (i.e., hard problems, like 6 +
      8 < 15, are solved more slowly than easy problems, like 2 + 4 < 07, suggesting
      that calculation takes longer). Analyses of latencies revealed three main
      results: First, split effects were of smaller magnitude in older adults compared
      to younger adults, whatever the type of arithmetic task; second, split effects
      were of smaller magnitude on easy problems; and third, calculation processes were
      well maintained in older adults with high level of arithmetic skills. This set of
      results improves our understanding of cognitive aging and strategy selection in
      arithmetic.

PMID- 16459898
TI  - Auditory attentional blink: masking the second target is necessary, delayed
      masking is sufficient.
AB  - When two target items (T1 and T2) are presented in rapid succession among
      fillers, processing T2 is often impaired. This phenomenon is known as the
      attentional blink (AB). Within the visual modality, this second-target deficit
      generally occurs only if T2 is masked by a trailing item. The current study was
      designed to examine whether masking of T2 also plays a critical role in the
      auditory AB. Results showed a reliable AB effect even when the item following T2
      was replaced by silence. However, the AB deficit was abolished when T2 was the
      last presented stimulus. Our results suggest that, as in vision, T2 masking is
      necessary for the AB to take place in audition, but that masking is effective
      even when delayed, providing evidence that the phenomenon shares some functional
      mechanisms across sensory modalities.

PMID- 16459899
TI  - 'Take me out coach'.

PMID- 16459900
TI  - The older nurse in the workplace: does age matter?
AB  - Between 2010 and 2020, over 40% of the RN workforce will be over 50 years of age,
      and many RNs are expected to retire and withdraw from the workforce. Given that
      older nurses are the fastest growing cohort of the workforce, the important
      findings presented in this article deserve careful consideration by policymakers,
      health care leaders, and managers.

PMID- 16459901
TI  - Cost of hospital care for elderly at risk of falling.
AB  - The variables that relate to cost of hospital care for a large sample of elderly
      patients at risk for falling are examined. The chief predictors of cost of
      hospitalization were medical, pharmacy, and nursing interventions. Use of nursing
      interventions, on average, raised the median hospital cost less than use of
      medical or pharmacy interventions. Using a standardized nursing language with the
      hospital's information system can provide nurses with information that
      demonstrates the cost effectiveness of their interventions.

PMID- 16459902
TI  - The economics of prescription drug prices, government intervention, and the
      importation of drugs from Canada.
AB  - Popular attention has focused on the skyrocketing health care costs in the United
      States and specifically on increasing insurance and prescription drug prices.
      Individuals and some local governments have advocated importing price-controlled
      prescription drugs from Canada to help ease the financial burden. What effects
      would this have on consumer prices, drug companies' incentives, and the
      development of new medications?

PMID- 16459903
TI  - Challenges for nursing in the 21st century.
AB  - Nurse leaders face a myriad of challenges in the 21st century such as nursing
      workforce shortages, negative affectivity, generation workforce concerns,
      changing delivery systems, and increasing clinical practice complexity, to name a
      few. Visionary and strategic thinking centered on patients' well-being are needed
      to tackle these challenges and shape a more humane and compassionate health care
      system.

PMID- 16459904
TI  - Defining quality of nursing work life.
AB  - As the largest single employee component of hospitals, nurses are critical to the
      functioning of the organization, and improving employee productivity continues to
      be a common theme in the health care literature. However, any increased
      productivity will be transitory if achieved at the expense of the quality of
      nurses' work life (QNWL), since improvement in the QNWL is prerequisite to
      improved productivity. The conceptual components of the concept of QNWL that
      differentiate QNWL from the concept job satisfaction are explored.

PMID- 16459905
TI  - Prevention: the most economical way to manage diabetes.

PMID- 16459907
TI  - Paving and resurfacing the road to Magnet.

PMID- 16459908
TI  - Patient safety: the four domains of nursing leadership.
AB  - The role of the nurse leader in patient safety can be characterized as follows:
      to establish the right culture; to infuse that culture with shared leadership so
      that the expert voice at the bedside is really defining the work; to possess the
      competencies necessary to coordinate and advance this complex initiative; and to
      forge both internal and external partnerships, because we will not be able to do
      this work alone. To further the work on this topic, nurse leaders who
      participated in the Nursing Leadership Congress are committed to identifying
      additional resources to help nurse leader colleagues drive patient safety efforts
      throughout their organizations.

PMID- 16459909
TI  - Establishing guardrails in leadership.
AB  - Shared leadership/governance offers the best environment for growth of the
      professional staff and for leaders and managers. Tisch (2004) writes that the
      power of the partnership begins with the recognition that no one can operate
      effectively in a vacuum and concludes with the premise that partnerships can
      redefine the traditional business relationships and transform them from
      adversarial to cooperative. This happens when the road is clearly delineated and
      guardrails are put in place as reminders of where the car should be on the road.
      With an atmosphere of learning and partnering to learn more, the leader's job
      becomes that of teacher, and mentor, and everyone is aligned around the journey
      to excellence with guardrails in place to monitor the journey.

PMID- 16459910
TI  - Just over the horizon.

PMID- 16459911
TI  - Stomal physic.

PMID- 16459912
TI  - Periodontitis as a risk factor for systemic disease: how strong is the evidence?

PMID- 16459913
TI  - Diabetes mellitus and the dental patient.
AB  - With the increasing number of diagnosed diabetics in the general population,
      dental health care providers can anticipate a greater number of diabetics in
      their practices. Familiarity with the systemic and oral signs and symptoms of DM
      may facilitate its diagnosis, and contribute to the quality of the individual's
      overall health. It is also important to be aware of the medications used to
      manage DM and the effect the disease and its treatment may have on dental
      treatment and scheduling of appointments. The dental provider may also be
      confronted with emergency management of the diabetic, with the most common
      condition being hypoglycemia. This paper has also reviewed the clinical signs and
      symptoms of this state and approaches to management.

PMID- 16459914
TI  - Periodontal disease and cardiovascular disease: is there an association?

PMID- 16459915
TI  - Pregnancy and the periodontium.

PMID- 16459916
TI  - Osteoporosis, estrogen replacement therapy, and the periodontium.

PMID- 16459918
TI  - Go ahead and be coy.

PMID- 16459919
TI  - Digital laser scans used in morphometric analysis of human skulls to demonstrate
      dental occlusal function III.

PMID- 16459920
TI  - Oral and maxillofacial pathology case of the month. Verruciform xanthoma.

PMID- 16459922
TI  - 9-trans, 11-trans-CLA: antiproliferative and proapoptotic effects on bovine
      endothelial cells.
AB  - Endothelial cell function can be influenced by nutrition, especially dietary FA
      and antioxidants. One class of dietary FA that is found in meat and dairy
      products derived from ruminant animals is conjugated linoleic acids (CLA). We
      have examined the effects of several CLA isomers on endothelial cell
      proliferation. 9t,11t-CLA was the only isomer that inhibited bovine aortic
      endothelial cell (BAEC) [3H]methylthymidine incorporation (I50 = 35 microM), and
      this antiproliferative effect was time-dependent. A small decrease (20%) in cell
      number was observed only at the highest concentration (60 microM) tested. The
      9c,11t-, 9c,11c-, 10t 12c-, and 11c,13t-CLA isomers did not exhibit any
      antiproliferative effects over a 5-60 microM concentration range. alpha
      Tocopherol and BHT decreased BAEC proliferation, but pretreatment of cells with
      either of these antioxidants substantially attenuated the antiproliferative
      effect of 9t,11 t-CLA. No difference in lipid peroxidation, as measured by the
      thiobarbituric acid assay for malondialdehyde, was observed on treatment of
      endothelial cells with either 9t,11 t- or 9c,11 t-CLA. However, a 43% increase in
      caspase-3 activity was observed after incubating BAEC with 9t,11 t-CLA,
      suggesting that the antiproliferative effect of this isomer is partially due to
      an apoptotic pathway. In contrast to the above results with normal endothelial
      cells, these five CLA isomers all inhibited proliferation of the human leukemic
      cell line THP-1, with the 9t,11 t isomer again being the most (I50 = 60 microM)
      effective. These results confirm that different CLA isomers have different
      inhibitory potencies on the proliferation of normal and leukemic cells.

PMID- 16459923
TI  - Intake of conjugated eicosapentaenoic acid suppresses lipid accumulation in liver
      and epididymal adipose tissue in rats.
AB  - It has been reported that consumption of CLA and EPA alters lipid metabolism. CLA
      contains conjugated double bonds, and EPA is an n-3 PUFA. Based on the
      possibility that a molecule with both of these structures might have interesting
      physiological effects, we prepared conjugated FA from EPA by alkaline
      isomerization and examined the effects of the conjugated EPA (CEPA) on lipid
      metabolism in rats. Rats were fed by oral gavage every day for 4 wk with 200 mg
      of FA including linoleic acid, EPA, CLA, or CEPA. Compared with other groups,
      rats fed CEPA showed a significant weight loss in epididymal adipose tissue and
      significant decreases in the levels of liver TAG and total cholesterol (TC),
      indicating reduced accumulation of lipid in the liver and adipose tissue. The
      plasma levels of TAG, TC, FFA, and tumor necrosis factor-alpha in rats fed CEPA
      were reduced, as was the activity of the FA synthesis system in the liver,
      whereas the FA-beta-oxidation system was activated by CEPA. These results suggest
      that intake of CEPA suppresses lipid accumulation in the liver and epididymal
      adipose tissue while increasing lipid catabolism in rats.

PMID- 16459924
TI  - Biochemical, functional, and histochemical effects of essential fatty acid
      deficiency in rat kidney.
AB  - The present study was designed to examine the effects of EFA deficiency (EFAD) on
      biochemical, functional, and structural aspects of the kidney in growing and
      adult rats fed a normal or EFAD diet for 9 wk after weaning. Food and fluid
      intake (F1), urine volume, and Na+ and K+ excretions were measured weekly from
      weeks 4 to 8 by placing the rats in individual metabolic cages for 24 h. At week
      9, Li+ and a 5% water load, respectively, were administered at 14 and 1.5 h prior
      to glomerular and proximal tubular function studies, as assessed by 3-h
      creatinine (C(Cr)) and Li+ (C(Li+)) clearances. Hematocrit and urine volume;
      serum and urine [Cr], [Li+], [Na+], and [K+]; and renal FA distribution were also
      measured. Data [corrected to 100 g/body weight (bw) and presented as means +/-
      SEM] were significant, at P< or = 0.05. Despite a similar ingestion of solids
      from weeks 4 to 7 (weeks 7 to 10 of life), the rats on the EFAD diet showed a
      decreased body weight from week 5. From weeks 4 to 8, Fl and urine volume were
      similar for both groups, but the Fl increased at week 6 in the EFAD group; 24-h
      Na+ and K+ excretions were similar at all weeks, except for an increase in the
      EFAD group for both ions at week 7. In the EFAD group, CCr and CLi+ decreased by
      27 and 56.3%, respectively (385.7 +/- 33.4 vs. 280 +/- 21.1, and 21.0 +/- 2.1 vs.
      9.2 +/- 1.1 microL/min/100 g; n = 9 vs. 10), the latter result suggesting
      increased proximal reabsorption. The 3-h Na+ and K+ excretions were similar, but
      the Li+ decreased (0.78 +/- 0.06 x 10(-2) vs. 0.32 +/- 0.03 x 10(-2)
      microeq/min/100 g) in the EFAD group, giving additional support to the
      suggestion. Renal structure was normal and similar for both groups, but the EFAD
      group showed a more prominent proximal tubule brush border, together with heavier
      periodic acid-Schiff staining in all specimens from weeks 5 to 9. In the EFAD
      group, FA of the n-9 and n-7 series were higher, but most of the n-6 series were
      lower as a percentage of total lipids in the medulla and cortex. Medullary levels
      of 20:4n-6 were maintained, 22:4n-6 declined twice, arachidonic acid was
      maintained, and 20:5n-3 was lower. The EFAD diet affected glomerular function,
      proximal tubular structure and function, and FA distribution in the rat kidney.

PMID- 16459921
TI  - Astonishing diversity of natural surfactants: 6. Biologically active marine and
      terrestrial alkaloid glycosides.
AB  - This review article presents 209 alkaloid glycosides isolated and identified from
      plants, microorganisms, and marine invertebrates that demonstrate different
      biological activities. They are of great interest, especially for the medicinal
      and/or pharmaceutical industries. These biologically active glycosides have good
      potential for future chemical preparation of compounds useful as antioxidants,
      anticancer, antimicrobial, and antibacterial agents. These glycosidic compounds
      have been subdivided into several groups, including: acridone; aporphine;
      benzoxazinoid; ergot; indole; enediyne alkaloidal antibiotics; glycosidic lupine
      alkaloids; piperidine, pyridine, pyrrolidine, and pyrrolizidine alkaloid
      glycosides; glycosidic quinoline and isoquinoline alkaloids; steroidal
      glycoalkaloids; and miscellaneous alkaloid glycosides.

PMID- 16459925
TI  - Parathyroid hormone stimulates phosphatidylethanolamine hydrolysis by
      phospholipase D in osteoblastic cells.
AB  - Parathyroid hormone (PTH) and phorbol-12,13-dibutyrate (PDBu) stimulate
      phospholipase D (PLD) activity and PC hydrolysis in UMR-106 osteoblastic cells
      {Singh, A.T., Kunnel, J.G., Strieleman, P.J., and Stern, P.H. (1999) Parathyroid
      Hormone (PTH)-(1-34), [Nle8,18,Tyr34]PTH-(3-34) Amide, PTH-(1-31) Amide, and PTH
      Related Peptide-(1-34) Stimulate Phosphatidylcholine Hydrolysis in UMR-106
      Osteoblastic Cells: Comparison with Effects of Phorbol 12,13-Dibutyrate,
      Endocrinology 140, 131-137}. The current studies were designed to determine
      whether ethanolamine-containing phospholipids, and specifically PE, could also be
      substrates. In cells labeled with 14C-ethanolamine, PTH and PDBu treatment
      decreased 14C-PE. In cells co-labeled with 3H-choline and 14C-ethanolamine, PTH
      and PDBu treatment increased both 3H-choline and 14C-ethanolamine release from
      the cells. Choline and ethanolamine phospholipid hydrolysis was increased within
      5 min, and responses were sustained for at least 60 min. Maximal effects were
      obtained with 10 nM PTH and 50 nM PDBu. Dominant negative PLD1 and PLD2
      constructs inhibited the effects of PTH on the phospholipid hydrolysis. The
      results suggest that both PC and PE are substrates for phospholipase D in UMR-106
      osteoblastic cells and could therefore be sources of phospholipid hydrolysis
      products for downstream signaling in osteoblasts.

PMID- 16459926
TI  - Lipid malabsorption persists after weaning in rats whose dams were given GLP-2
      and dexamethasone.
AB  - Glucagon-like peptide-2 (GLP-2) enhances intestinal growth and absorption in
      mature animals, and glucocorticosteroids (GC) increase the sugar and lipid uptake
      in adult animals. However, the role of GC and GLP-2 in the ontogeny of lipid
      absorption is unknown. We hypothesized that GLP-2 and the GC dexamethasone (DEX),
      when administrated to rat dams during pregnancy and lactation, would enhance
      lipid uptake in the offspring. Rat dams were treated in the last 10 d of
      pregnancy and during lactation with GLP-2 [0.1 microg/g/d subcutaneous (sc)], DEX
      (0.128 microg/g/d sc), GLP-2 + DEX, or a placebo. Sucklings were sacrificed at 19
      21 d of age, and weanlings were sacrificed 4 wk later. Lipid uptake was assessed
      using an in vitro ring uptake method. Although DEX and GLP-2 + DEX increased the
      jejunal mass, the jejunal lipid uptake was unchanged. In contrast, GLP-2, DEX,
      and GLP-2 + DEX reduced the ileal lipid uptake in suckling and weanling rats.
      This reduction was not due to alterations in intestinal morphology or to changes
      in fatty acid-binding protein abundance, but it was partially explained by an
      increase in the effective resistance of the intestinal unstirred water layer. In
      sucklings, DEX dramatically reduced the jejunal lipid uptake to levels similar to
      those seen in weanlings, such that the normal ontogenic decline in lipid uptake
      was not observed. Giving dams GLP-2 or DEX during pregnancy and lactation reduced
      lipid uptake in the offspring, and this persisted for at least 1 mon. The impact
      this may have on the nutritional well-being of the animal in later life is
      unknown.

PMID- 16459928
TI  - Synthesis of dihydroperoxides of linoleic and linolenic acids and studies on
      their transformation to 4-hydroperoxynonenal.
AB  - The cytotoxic aldehydes 4-hydroxynonenal, 4-hydroperoxynonenal (4-HPNE), and 4
      oxononenal are formed during lipid peroxidation via oxidative transformation of
      the hydroxy or hydroperoxy precursor fatty acids, respectively. The mechanism of
      the carbon chain cleavage reaction leading to the aldehyde fragments is not
      known, but Hock-cleavage of a suitable dihydroperoxide derivative was implicated
      to account for the fragmentation [Schneider, C., Tallman, K.A., Porter, N.A., and
      Brash, A.R. (2001) Two Distinct Pathways of Formation of 4-Hydroxynonenal.
      Mechanisms of Nonenzymatic Transformation of the 9- and 13-Hydroperoxides of
      Linoleic Acid to 4-Hydroxyalkenals, J. Biol. Chem. 275, 20831-20838]. Both 8,13-
      and 10,13-dihydroperoxyoctadecadienoic acids (diHPODE) could serve as precursors
      in a Hock-cleavage leading to 4-HPNE via two different pathways. Here, we
      synthesized diastereomeric 9,12-, 10,12-, and 10,13-diHPODE using singlet
      oxidation of linoleic acid. 8,13-Dihydroperoxyoctadecatrienoic acid was
      synthesized by vitamin E-controlled autoxidation of gamma-linolenic acid followed
      by reaction with soybean lipoxygenase. The transformation of these potential
      precursors to 4-HPNE was studied under conditions of autoxidation, hematin-, and
      acid-catalysis. In contrast to 9- or 13-HPODE, neither of the dihydroperoxides
      formed 4-HPNE on autoxidation (lipid film, 37 degrees C), regardless of whether
      the free acid or the methyl ester derivative was used. Acid treatment of 10,13
      diHPODE led to the expected formation of 4-HPNE as a significant product, in
      accord with a Hock-type cleavage reaction. We conclude that, although the
      suppression of 4-H(P)NE formation from monohydroperoxides by alpha-tocopherol
      indicates peroxyl radical reactions in the major route of carbon chain cleavage,
      the dihydroperoxides previously implicated are not intermediates in the
      autoxidative transformation of monohydroperoxy fatty acids to 4-HPNE and related
      aldehydes.

PMID- 16459927
TI  - Immediate no-flow ischemia decreases rat heart nonesterified fatty acid and
      increases acyl-CoA species concentrations.
AB  - Tissues changes in FA metabolism can occur quite rapidly in response to ischemia
      and may require immediate microwave fixation to determine basal concentrations.
      The present study aimed to quantify the effects of immediate no-flow ischemia on
      concentrations of individual nonesterified FA (NEFA) and acyl-CoA species in the
      rat heart. Male CDF 344 rats were anesthetized and decapitated either 5 min prior
      to being microwaved (5.5 kW, 3.4 s, twice) to produce ischemia or microwaved
      prior to decapitation (nonischemic). Hearts were then removed and used to measure
      the concentrations of acyl-CoA species and FA in several lipid classes. The
      ischemic heart total NEFA concentration was significantly lower than that in the
      nonischemic heart (11.9 vs. 19.0 nmol/g). Several individual NEFA concentrations
      were decreased by 31-85%. Ischemic heart total long-chain acyl-CoA concentrations
      (21.0 nmol/g) were significantly higher than those in nonischemic hearts (11.4
      nmol/g). Increased concentrations of individual acyl-CoA species occurred in
      palmitoyl-CoA, stearoyl-CoA, oleoyl-CoA, and linoleoyl-CoA. Concentrations of
      short-chain acetyl-CoA and beta-hydroxy-beta-methylglutaryl-CoA were also two- to
      three-fold higher in ischemic hearts than in nonischemic hearts. The FA
      concentration in TG and phospholipids generally did not differ between the
      groups. Decreases in concentrations of individual FA and increases in acyl-CoA
      species during no-flow ischemia occur very rapidly within the heart. Although it
      is not clear how these alterations contribute to the pathogenesis of ischemia, it
      is evident that future studies attempting to quantify basal levels of these
      metabolites could use microwave fixation.

PMID- 16459929
TI  - Conversion of linoleic acid into novel oxylipins by the mushroom Agaricus
      bisporus.
AB  - Oxylipins are associated with important processes of the fungal life cycle, such
      as spore formation. Here, we report the formation of FA metabolites in Agaricus
      bisporus. Incubation of a crude extract of lamellae with linoleic acid (18:2) led
      to the extensive formation of two oxylipins. They were identified as 8(R)-hydroxy
      9Z,12Z-octadecadienoic acid (8-HOD) and 8(R),11 (S)-dihydroxy-9Z,12Z
      octadecadienoic acid (8,11-diHOD) by using RP-HPLC, GC-MS, IR, GC-MS analysis of
      diastereomeric derivatives, and 1H NMR and 13C NMR spectroscopy. Neither compound
      has been reported before in A. bisporus. Oleic (18:1), alpha-linolenic (18:3n-3),
      and gamma-linolenic (18:3n-6) acids were converted into their 8-hydroxy
      derivatives as well, and 18:3n-3 was further metabolized to its 8,11-diol
      derivative. Reactions with [U-13C]18:2 demonstrated that the compounds 8-HOD and
      8,11-diHOD were formed from exogenously supplied 18:2. When [U-13C]8-HOD was
      supplied, it was not converted into 8,11-diHOD, indicating that it was not an
      intermediate in the formation of 8,11-diHOD. When a crude extract of A. bisporus
      was incubated under an atmosphere of 16O2/18O2, the two hydroxyl groups of 8,11
      diHOD contained either two 180 atoms or two 60 atoms. Species that contained one
      of each isotope could not be detected. We propose that the formation of the 8,11
      dihydroxy compounds occurs through either an 8,11-endoperoxy, an 8-peroxo free
      radical, or an 8-hydroperoxy intermediate. In the latter case, the reaction
      should be catalyzed by dioxygenase with novel specificity.

PMID- 16459931
TI  - 4-Hydroxy-3-methoxycinnamate esters of milkweed oil: synthesis and
      characterization.
AB  - The common milkweed (Asclepias syriaca L.) is a new industrial crop. Its seed oil
      (TAG) is highly polyunsaturated. In the search for novel applications for
      milkweed seed oil, the olefinic groups in the TAG were oxidized to polyhydroxy
      TAG via epoxidation and subsequent epoxy ring-opening reactions. These
      polyhydroxy TAG exhibit unique industrially desirable emulsoid properties in
      water. Esterification of the secondary polyhydroxy functionalities of the TAG
      derivatives of the oil with trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid)
      has resulted in the development of novel cinnamate esters of milkweed oil. These
      cinnamates are also obtainable via direct ring-opening of the epoxy TAG
      intermediate with ferulic acid. Among the interesting characteristics of the
      ester derivatives is their UV radiation-absorbing property.

PMID- 16459930
TI  - Inhibition of 12- and 15-lipoxygenase activities and protection of human and
      tilapia low density lipoprotein oxidation by I-Tiao-Gung (Glycine tomentella).
AB  - I-Tiao-Gung, Glycine tomentella, has been used extensively as a traditional
      herbal medicine to relieve physical pain, but its bioactivity has not been
      studied systematically. Ninety-five percent ethanol extracts of G. tomentella (GT
      E) showed antioxidant activity in human plasma by prolonging the lag phase
      (+Tlag) of Cu2+-induced LDL oxidation and were dose dependent. The +Tlag of LDL
      combined with 3.2 microg/mL GT-E was similar to that with 2.0 microM (ca. 0.5
      microg/mL) Trolox. A similar inhibitory effect was found toward tilapia plasma
      LDL. In addition, GT-E inhibited tilapia thrombocyte (nucleated platelet) 5-, 12
      , and 15-lipoxygenase (LOX). The IC50 values were 0.43, 0.72, and 0.42 microg/mL,
      respectively, whereas the IC50 values for nordihydroguaiaretic acid (NDGA) on 5-,
      12-, and 15-LOX were 2.3, 1.6, and 1.7 microg/mL, respectively. The IC50 value
      for cyclooxygenase-2 (COX-2) inhibition by GT-E was 42.0 microg/mL, whereas the
      IC50 value by indomethacin as a positive control was 0.61 microLg/mL. The
      prevention of LDL oxidation and the dual inhibition of LOX and COX-2 are
      indicative of the possible roles of I-Tiao-Gung in antiatherosclerosis and anti
      inflammation.

PMID- 16459933
TI  - Heavy and nonheavy drinking occasions, all-cause and cardiovascular mortality and
      hospitalizations: a follow-up study in a population with a low consumption level.
AB  - OBJECTIVE: The purpose of this study was to separate the effects of heavy and
      nonheavy episodic drinking on mortality and hospitalizations from ischemic heart
      disease (IHD) and other cardiovascular disease (OCVD) and on all-cause mortality.
      METHOD: The respondents in Finnish drinking habit surveys in 1969, 1976 and 1984
      (N = 6,394) were followed up for mortality and hospitalizations. There were 1,144
      total deaths from all causes, 854 hospitalizations or deaths from IHD and 1,270
      from OCVD. The main variables included total volume of consumption and total
      volume divided into volume consumed on heavy drinking occasions and nonheavy
      drinking occasions. Four alternative measures of heavy episodic drinking (HED)
      were also used. RESULTS: Among males, the total volume of consumption showed a
      protective effect against IHD. A high volume consumed on light drinking occasions
      was associated with a decreased risk of IHD (hazard ratio [HR] = 0.56, confidence
      interval [CI]: 0.34-0.92) and an increased risk of OCVD (HR = 1.48, CI: 1.00
      2.18). A high volume consumed on heavy drinking occasions was associated with an
      increased risk of all-cause mortality (HR = 1.34, CI: 1.04-1.73). Among females,
      a protective effect of total and non-HED volume against all-cause mortality and
      non-HED volume against IHD was observed. CONCLUSIONS: The findings contribute to
      the cumulating evidence that drinking pattern matters. Moderate drinking is
      associated with a lower risk of IHD, whereas drinking in a heavy episodic manner
      (often referred to as "binge drinking") is not. The results underline the
      importance of considering, in addition to the volume of consumption, the pattern
      of drinking in epidemiological studies.

PMID- 16459932
TI  - Cross-sectional and longitudinal relationships between alcohol consumption and
      lipids, blood pressure and body weight indices.
AB  - OBJECTIVE: Serum lipids, blood pressure and body mass may mediate the U-shaped
      relationship of alcohol consumption with type 2 diabetes mellitus and coronary
      heart disease. This study examines the cross-sectional and long-term longitudinal
      relationships of (changes in) alcohol consumption with (changes in) serum lipids,
      blood pressure and body mass indices. METHOD: In this prospective, observational
      cohort study, two measurements of alcohol consumption, serum total and high
      density lipoprotein cholesterol, triglycerides, blood pressure, body weight, the
      thickness of four skinfolds and waist circumference were performed 4 years apart
      in healthy volunteers (143 men and 174 women, 32 years old at the first
      measurement). Alcohol consumption from beer, wine and distilled spirits was
      assessed using an extensive dietary history interview. Linear regression analyses
      were performed to study the cross-sectional relationships between the amount of
      alcohol consumed at the age of 32 years and the levels of the lipids, blood
      pressure and body weight indices, and to study the longitudinal relationships
      between the changes in the amount of alcohol consumed over the 4 years of follow
      up and the concurrent changes in the lipids, blood pressure and body weight
      indices. Nonlinearity was investigated for the cross-sectional relationships.
      RESULTS: A 10-g/day difference in alcohol consumption was positively related with
      a 0.05 mmol/L (1.9 mg/dl) difference in high-density lipoprotein cholesterol in
      both cross-sectional (p = .004), and longitudinal (p < .0001) analyses. This
      relationship did not differ for men and women or for the consumption of beer,
      wine or distilled spirits. Relationships with changes in total cholesterol,
      triglycerides, systolic, diastolic, and pulse pressure, body weight and the sum
      of four skinfolds were not significant. A borderline significant inverse
      longitudinal relationship was found with waist circumference. The other lifestyle
      behaviors (tobacco smoking, physical activity and dietary habits) were major
      confounders of most cross-sectional relationships between alcohol and serum
      lipids, blood pressure and body mass indices. The longitudinal relationships,
      however, were not confounded by changes in the other lifestyle behaviors. A
      significant nonlinear relationship was found for systolic blood pressure, in
      which drinkers of about 30 g/day had the lowest values. CONCLUSIONS: Moderate
      alcohol consumption and moderate long-term changes in alcohol consumption are
      positively related with the levels and changes in high-density lipoprotein
      cholesterol in healthy adult men and women. A moderate inverse association
      between alcohol and waist circumference may be expected. No relationships were
      found with triglycerides, blood pressure, body weight and the sum of the
      thickness of four skinfolds. Other lifestyle behaviors confound the cross
      sectional, but not the longitudinal, relationships between alcohol consumption
      and serum lipids, blood pressure and body mass indices. Gender and type of
      beverage do not modify the relationships between alcohol consumption and these
      indices.

PMID- 16459934
TI  - Effects of early and later marriage on women's alcohol use in young adulthood: a
      prospective analysis.
AB  - OBJECTIVE: Previous research shows that marriage leads to reductions in alcohol
      use, especially for women. Because marriage prior to age 20 (early marriage) is a
      marker for deviance, the protective effects of marriage may not extend to those
      who marry in adolescence. We compared the effects of marriage in adolescence
      versus young adulthood on alcohol consumption, negative alcohol-related
      consequences and heavy episodic drinking at age 29. METHOD: We analyzed data from
      1,138 women in a longitudinal cohort followed from ages 18 to 29. The original
      sample was recruited from 30 California and Oregon middle schools and first
      surveyed at age 13. RESULTS: Women who had not married, had married early or had
      married between ages 20 and 29 did not differ on alcohol use at age 18. Women who
      married as young adults were less likely than singles to engage in any alcohol
      use, heavy episodic drinking or experience negative consequences and reported
      less alcohol use at age 29. Women who married in adolescence reported fewer
      negative consequences at age 29 than did singles and (if they had not divorced)
      were less likely to engage in heavy episodic drinking or experience any negative
      consequences, reported fewer consequences and consumed less alcohol. The
      protective effects of marriage in young adulthood were observed whether or not
      women divorced. Parenthood and college attendance before age 23 did not explain
      the marriage effect. CONCLUSIONS: Results support role theory, which posits that
      individuals who marry are socialized into conventional adult roles that
      discourage deviant behavior.

PMID- 16459935
TI  - Alcohol elimination at low blood concentrations among women taking combined oral
      contraceptives.
AB  - OBJECTIVE: Evidence implicating a role of natural and synthetic estrogens and/or
      progestin on ethanol pharmacokinetics can be traced back to the mid-1970s when
      reports of large metabolic differences were found suggesting that sex hormones
      interfered with the efficient clearance of alcohol at the liver microsomal level.
      Research teams in this area manipulate sex hormone levels by either examining
      natural-cycling women at different phases of their menstrual cycle or others
      taking oral contraceptives that synthetically regulate the hormonal fluctuations.
      These collective studies (over a dozen to date involving over 200 participants)
      have all been similar in focus and outcome. With one important exception, the
      published laboratory research since 1976 has failed to replicate the earliest
      research suggesting sex hormone effects. One well-controlled study in 1987 did
      generate renewed interest in the area with the paradoxical finding that
      progesterone actually enhanced alcohol elimination at low blood concentrations
      (<.025%). The present study represented the most direct attempt to replicate this
      particular finding using 5-minute breath alcohol readings that extended below
      blood alcohol concentrations of .025%. METHOD: A total of 17 women taking
      combined oral contraceptives were tested during both menstruation and the luteal
      phase (Days 16-22) of their cycle in counterbalanced sequence. RESULTS:
      Pharmacokinetics differences were not found. CONCLUSION: These results contribute
      further to a literature base demonstrating the limited effects of both natural
      and synthetic sex hormones on alcohol metabolism in women.

PMID- 16459936
TI  - Drinking trajectories from adolescence to the mid-forties among alcohol dependent
      males.
AB  - OBJECTIVE: Identifying differing developmental trajectories of alcohol behavior
      is fundamental in building theories of alcoholism etiology and course. The
      purpose of this study was to identify differences in developmental pathways of
      alcoholism from onset of drinking into middle adulthood. METHOD: Alcohol-related
      behaviors and psychiatric status were assessed in 330 men from the Vietnam Era
      Twin Registry having a lifetime diagnosis of alcohol dependence (AD). Using a
      modified version of Skinner's Lifetime Drinking History, distinct drinking phases
      were identified that differed in terms of quantity, frequency and context of
      drinking. Person-year data were created to indicate whether AD criteria were or
      were not met for each year between drinking onset and age 41. RESULTS: Using
      Latent Growth Mixture Modeling, a four-class model was identified: Severe Chronic
      Alcoholics; Severe Non-Chronic Alcoholics (SNCA); Late Onset Alcoholics; and
      Young Adult Alcoholics. Counterparts for three trajectories could be found in the
      larger alcoholism literature, whereas the fourth type (SNCA) has not been
      described, notwithstanding its seeming importance and prevalence. CONCLUSIONS:
      Present findings support the existence of different alcoholism trajectories and
      provide a more complete understanding of the variability of alcohol dependence
      over time. Findings build on the larger alcoholism literature identifying
      alcoholic subgroups and provide important information regarding alcoholism
      trajectories and associated features. Future studies are needed with regard to
      better understanding of the psychosocial influences related to the different
      alcoholism trajectories, as well as characterizing the different trajectories as
      individuals transition into older age.

PMID- 16459937
TI  - Sequencing the lifetime onset of alcohol-related symptoms in older adults: is
      there evidence of disease progression?
AB  - OBJECTIVE: The purpose of this study was to evaluate evidence of orderly symptom
      progression in alcohol-use disorders (disease-progression model). METHOD: A
      sample of community-residing older problem drinkers provided information about
      their life history of drinking, including the age at which they had experienced
      alcohol-related symptoms that correspond to criteria for alcohol abuse and
      dependence. Symptom sets and possible sequences were formulated separately for
      women and men, based on the average number of years from drinking initiation to
      symptom onset and on symptom prevalence. We assessed how well the ordering of
      symptoms experienced by individual respondents matched the sequences derived with
      these group-level measures; we also assessed whether individuals progress from
      alcohol abuse to dependence as is implied in some conceptualizations of alcohol
      use disorders. RESULTS: Half or more of these older adults experienced symptom
      onset in an order that was inconsistent with the possible symptom sequences
      derived from group-level analysis (e.g., reversals from the expected order or
      concurrent onset of symptoms expected to occur sequentially). Similarly, alcohol
      abuse did not appear to be a precursor to the development of alcohol dependence
      in individual patterns of symptom onset. CONCLUSIONS: Although group-level
      results based on the number of years from drinking initiation to symptom onset or
      on symptom prevalence may seem to point to orderly progression in the development
      of alcohol-related symptoms, these group-level results do not capture individual
      experiences very well. In this community-residing sample of problem drinkers,
      most of whom had never sought treatment, there was marked variability in the
      course of symptom development, which raises questions about the utility of a
      disease-progression model.

PMID- 16459938
TI  - Processes linking adolescent problems to substance-use problems in late young
      adulthood.
AB  - OBJECTIVE: The current study explores three avenues in early young adulthood
      through which adolescent problems may be linked to later substance use problems:
      problematic substance use, failure to assume adult roles and responsibilities,
      and exposure to pro-drug social influences. METHOD: Participants (N = 1,986; 49%
      female) filled out surveys at ages 18, 23 and 29. Participants were 67% white, 9%
      black, 10% Hispanic and 8% Asian. Deviance, poor mental health, substance use,
      alcohol and other drug (AOD) problems, and school dropout were measured at age
      18. AOD problems were also measured at age 23, as were role changes (e.g.,
      marriage) and pro-drug social influences (e.g., friends use drugs). Indicators of
      substance abuse and dependence were measured at age 29. Demographics and family
      history of AOD were covariates. RESULTS: Reporting more deviant behavior and
      heavier drinking at age 18 was associated with a higher likelihood of abuse and
      dependence at age 29. Alcohol use and pro-drug social influences at age 23
      appeared to mediate the effects of adolescent substance use; lack of role
      assumption did not. The effect of poor mental health at age 18 was not mediated
      by any set of variables but instead appeared to directly predict dependence at
      age 29. CONCLUSIONS: Findings highlight the importance of early young adult
      drinking and substance-using peers in continuing patterns of heavy substance use
      developed during adolescence and also underscore the long-term impact of poor
      mental health during adolescence on substance use problems in late young
      adulthood.

PMID- 16459939
TI  - Risk factors for frequent high alcohol consumption among Swedish secondary-school
      students.
AB  - OBJECTIVE: The aim of this study was to analyze the impact and possible causal
      interrelationships of psychological, psychosocial and socioeconomic factors on
      frequent high consumption of alcoholic beverages in a Swedish secondary-school
      student population. METHOD: A cross-sectional study via questionnaire was
      administered to 1,384 high school students in Trelleborg, Sweden, from 1999 to
      2001 (658 boys, 726 girls; response rates, 84.6% in 1999, 89.3% in 2000 and 91.7%
      in 2001). Logistic regression analyzed the relationship between various risk
      factors and frequent high alcohol consumption. RESULTS: Interest in trying drugs
      was the strongest indicator for frequent high alcohol consumption, after
      adjusting for age, socioeconomic status and psychosocial risk factors (boys: odds
      ratio (OR) = 3.9, 95% confidence interval (CI): 2.5-6.0; girls: OR = 2.7, 95% CI:
      1.8-3.9). This variable also had the highest population-attributable fraction
      (PAF; boys = 39%, girls = 29%). High purchasing power increased the risk of
      frequent high alcohol consumption (boys: OR = 2.1, 95% CI: 1.4-3.0; PAF = 25%;
      girls: OR = 1.6, 95% CI: 1.1-2.3; PAF = 16%). The association between high
      alcohol consumption and psychosocial factors differed by gender. Participation in
      organized team sports was associated with increased risk among boys (OR = 3.0,
      95% CI: 2.0-4.7; PAF = 32%), but not girls (OR = 1.0, 95% CI: 0.7-1.5; PAF = 0%).
      Parental acceptance of alcohol consumption was more important for the latter
      (girls: OR =1.7, 95% CI: 1.2-2.3; PAF = 27%; boys: OR = 1.5, 95% CI: 1.0-2.1; PAF
      = 21%). CONCLUSIONS: Psychological, psychosocial and socioeconomic elements were
      independent risk factors for frequent high alcohol consumption. Discrepancies in
      risk factor patterns between boys and girls suggest alternate approaches be
      considered in interventiods.

PMID- 16459940
TI  - Part-time work and adolescent heavy episodic drinking: the influence of family
      and community context.
AB  - OBJECTIVE: Previous studies on part-time work and alcohol use suggest that
      teenagers who work longer hours drink more heavily. The purpose of this study was
      to investigate whether family- and community-level factors moderate the
      relationship between part-time work hours and heavy episodic drinking. METHOD:
      Data were drawn from the Canadian Community Health Survey, a cross-sectional
      study of a nationally representative sample of Canadians. The survey included
      8,080 respondents 15-19 years of age who reported work hours and frequency of
      heavy episodic drinking over the past 12 months. These respondents were located
      in 136 counties or municipalities across Canada. RESULTS: On average, work hours
      were positively associated with the frequency of heavy drinking by teenagers in
      the past 12 months. At the community level, the proportion of teenagers in each
      community drinking any alcohol was independently and positively associated with
      respondents' frequency of heavy drinking. In terms of moderating effects, we
      found that the work hours-drinking association was weaker among youth from low
      socioeconomic status families. Examination of community-level factors indicated
      that longer work hours were more strongly associated with heavy episodic drinking
      in communities with high rates of teen alcohol abstinence. CONCLUSIONS: Although
      the cross-sectional data prohibit any firm conclusions on how family and
      community factors influence the work-alcohol use relationship, these data suggest
      that interventions to reduce heavy episodic drinking among teens should address
      the broader environmental as well as the individual determinants.

PMID- 16459941
TI  - Incidence rates for alcohol dependence among adults: prospective data from the
      Baltimore Epidemiologic Catchment Area Follow-Up Survey, 1981-1996.
AB  - OBJECTIVE: Using prospectively gathered data, we assessed cumulative incidence of
      alcohol dependence using the Diagnostic Interview Schedule (DIS) based on
      criteria from the Diagnostic and Statistical Manual of Mental Disorders, Revised
      Third Edition (DSM-III-R). METHOD: Probability samples of area residents were
      selected by census tracts and households in five communities of the Epidemiologic
      Catchment Area Survey program. The baseline interview for the Baltimore site was
      completed in 1981, and between 1993 and 1996 the original Baltimore site cohort
      was traced. After excluding individuals with current or prior history of alcohol
      dependence at the time of the baseline interview, we identified a cohort of 1,642
      individuals who were at risk for alcohol dependence. Person-years of risk were
      calculated, cumulative incidence obtained, and survival analyses completed.
      RESULTS: Several principal findings that confirm some from studies of shorter
      follow-up intervals are as follows: (1) incidence of alcohol dependence is
      consistently greater for men and generally decreases with age; (2) problem
      drinkers have the highest incidence of dependence, and the male-to-female ratio
      is attenuated in this group; (3) no differences were found for risk of dependence
      by racial group; and (4) predictors of alcohol dependence include male gender,
      young age, not being married and having a history of tobacco smoking.
      CONCLUSIONS: The current study supplies data on the rate of development of
      DIS/DSM-III-R alcohol dependence in a population-based sample with an extended
      interval of follow-up. Methodological considerations in the analysis and
      interpretation of this type of prospectively gathered data are discussed.

PMID- 16459943
TI  - "So I can't blame the booze?": Dispositional aggressivity negates the moderating
      effects of expectancies on alcohol-related aggression.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of alcohol
      expectancies on intoxicated aggression in men and women while controlling for
      dispositional aggressivity. METHOD: Subjects were 328 (163 men and 165 women)
      healthy social drinkers between 21 and 35 years of age. Alcohol expectancies were
      measured using items from a variety of validated self-report inventories.
      Following the consumption of either an alcohol or a placebo beverage, subjects
      were tested on a modified version of the Taylor Aggression Paradigm, in which
      mild electric shocks were received from and administered to a fictitious opponent
      during a competitive task. Aggressive behavior was operationalized as the shock
      intensities administered to the fictitious opponent under conditions of low and
      high provocation. RESULTS: On their own, alcohol expectancies played a limited
      role in impacting aggressive behavior. Specifically, alcohol expectancies were
      significantly related to aggression for men who received the placebo beverage
      under low provocation and for men who received alcohol under high provocation. A
      significant main effect of alcohol expectancies was also detected. However, all
      of these effects were rendered nonsignificant when controlling for dispositional
      aggressivity. It is important to note that the main effect for beverage group
      remained significant after controlling for dispositional aggressivity.
      CONCLUSIONS: Taken as a whole, this pattern of findings suggests that intoxicated
      aggression is primarily the result of alcohol's pharmacological properties in
      conjunction with an aggressive personality.

PMID- 16459942
TI  - Overserving at licensed premises in Stockholm: effects of a community action
      program.
AB  - OBJECTIVE: The aim of this research was to study the sustainable effects of a
      community action program on alcohol service to intoxicated patrons at licensed
      premises. METHOD: Since 1996, the hospitality industry and authorities in
      Stockholm, Sweden, have been cooperating to reduce problems related to alcohol
      consumption at licensed premises. The intervention has included community
      mobilization, training in responsible beverage service (RBS) and enforcement. A
      pretest in 1996 and follow-ups in the 1999 and 2001 designs were used to study
      licensed premises in Stockholm. Male actors portraying intoxicated patrons
      visited the licensed premises and attempted to order beer. Observers were present
      at each visit. At the pretest, 92 licensed premises were visited, 47 in north
      central Stockholm and 45 in south central Stockholm. In 1999, 103 establishments
      were visited, 61 in north central Stockholm and 42 in south central Stockholm. At
      the latest follow-up in 2001, 100 licensed premises were visited, 56 in north
      central Stockholm and 44 in south central Stockholm. RESULTS: The results from
      the latest follow-up in 2001 showed a statistically significant improvement over
      those of earlier measures, with a refusal rate of 70% compared with 47% in 1999
      and 5% in 1996. There were improvements in both study areas (i.e., north and
      south central Stockholm). CONCLUSIONS: There has been a significant improvement
      in the rate of refusal of alcohol service at licensed premises in Stockholm
      during the project period. The reason for this is probably a combination of the
      intervention efforts: community mobilization, RBS training and a more efficient
      monitoring of alcohol service by authorities.

PMID- 16459944
TI  - An examination of how therapist directiveness interacts with patient anger and
      reactance to predict alcohol use.
AB  - OBJECTIVE: This study examined the interactions of therapist directiveness with
      patient anger and patient reactance among an alcohol-treatment-seeking sample.
      METHOD: Participants in the study consisted of 139 individuals with alcohol abuse
      or dependence who received treatment at a single clinical research unit of
      Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). Analyses
      tested for the independence of the two interactions, identified components within
      the directiveness construct and examined the relationship between those
      components and the patient attributes. RESULTS: Results showed that the
      interactions between directiveness and anger and between directiveness and
      reactance each accounted for unique variance in predicting posttreatment alcohol
      use as measured by percentage of days abstinent (PDA) and percentage of heavy
      drinking days (PHDD). Principal components analysis of the directiveness
      construct generated two underlying components that were interpreted to be
      confrontation and structure. Significant interactions were observed between
      patient reactance and both the confrontation and structure components.
      Confrontation also interacted with patient anger; however, no interaction was
      found between anger and structure. CONCLUSIONS: The interactions of therapist
      directiveness with patient anger and reactance demonstrated both shared and
      unique qualities. These results highlight the importance of focusing on specific
      aspects of directiveness to better understand the effect of patient-treatment
      interactions on alcohol use. This study has implications for theory and research
      as well as for the delivery of treatment services.

PMID- 16459945
TI  - The efficacy of compliance therapy in pharmacotherapy for alcohol dependence: a
      randomized controlled trial.
AB  - OBJECTIVE: This study sought to evaluate the effectiveness of compliance therapy
      in increasing adherence to pharmacological treatment for alcohol dependence.
      METHOD: Forty subjects were randomly allocated to receive usual medical care (n =
      20) or usual medical care plus compliance therapy (n = 20). All subjects were
      prescribed acamprosate (Campral) for 4 months. Subjects were volunteers treated
      at a hospital-based outpatient drug and alcohol treatment service, and were men
      and women who were 18-65 years old and with a Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition, diagnosis of alcohol dependence. All
      subjects received usual medical care consisting of seven medical reviews
      (duration = 15 minutes) over 4 months. Compliance therapy consisted of four to
      six individual sessions (duration = 60 minutes) in which beliefs about medication
      side effects, ambivalence, the benefits of treatment, treatment maintenance and
      relapse prevention were addressed and explored with motivational interviewing and
      cognitive behavior therapy techniques. RESULTS: The outcome variables were number
      of days taking acamprosate, days to first drink, days to first relapse (more than
      five drinks) and days to first extended relapse (greater than 2 consecutive days
      of more than five drinks). Intention-to-treat analyses showed little difference
      between the two groups in the outcome drinking measures. Nevertheless, the per
      protocol analyses revealed that participation in three or more sessions of
      compliance therapy significantly increased adherence to acamprosate and improved
      overall treatment outcomes. CONCLUSIONS: The present study highlights the need
      for psychological interventions to improve adherence to pharmacotherapy in the
      treatment of alcohol dependence and provides initial support for compliance
      therapy as an effective intervention.

PMID- 16459946
TI  - Readmission among chemical dependency patients in private, outpatient treatment:
      patterns, correlates and role in long-term outcome.
AB  - OBJECTIVE: Similar to other chronic conditions, chemical dependency is a chronic,
      relapsing condition. Yet predominant treatment models do not provide ongoing,
      long-term treatment services; readmission is the available long-term care for
      alcohol and drug patients. We examine readmission patterns and the role of
      readmission in 5-year outcome in chemical dependency patients in a private,
      integrated health plan. METHOD: We used health plan utilization databases and
      self-report at 5-year follow-up to measure readmission and routine primary care
      services in 647 chemical dependency outpatients from a private health plan.
      Logistic regression was used to examine whether readmission and primary medical
      care predicted abstinence at 5 years. RESULTS: Controlling for demographic
      characteristics and dependence type, higher odds for past-year alcohol and drug
      abstinence at 5 years following treatment was predicted by having been readmitted
      in the first 4 years after index episode (odds ratio =1.59, p = .006). Receiving
      routine medical care predicted past 30-day (but not past-year) abstinence at 5
      year follow-up. CONCLUSIONS: The relationship of readmissions to better outcome
      at 5 years suggests that long-term continuing care may benefit patients' long
      term outcomes. More research is needed on the relationship of primary medical
      care to long-term outcome in chemical dependency patients.

PMID- 16459947
TI  - Beliefs as a predictor of relapse in alcohol-dependent Turkish men.
AB  - OBJECTIVE: The aim of the current study was to evaluate the role of beliefs about
      alcohol use and craving on predicting relapse as stated in Beck's cognitive
      theory of alcoholism in detoxified alcohol-dependent patients. METHOD: Seventy
      male participants who were alcohol dependent according to the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and who were
      admitted to an inpatient unit for alcohol detoxification were studied at baseline
      and at 6 months follow-up. Participants were administered the Structured Clinical
      Interviews for DSM-IV axis I and DSM-III-R axis II Disorders (SCID-I and SCID-II,
      respectively), the Beck Anxiety Inventory and the revised Clinical Institute
      Withdrawal Assessment for Alcohol (CIWA-Ar). Beliefs about alcohol use were
      assessed with the Beliefs About Substance Use Inventory and the Craving Beliefs
      Questionnaire (CBQ). RESULTS: The relapse rate of the study group was 84.1% (58
      patients). The age of onset of alcohol dependence and age at first
      hospitalization were lower in patients who relapsed. The severity of physical
      dependence and presence of comorbid antisocial personality disorder were higher
      in the relapse group. In addition, patients who relapsed had higher scores in the
      CBQ. According to logistic regression analysis, craving beliefs and the degree of
      physical dependence were predictors of relapse in alcoholic patients.
      CONCLUSIONS: Our findings suggest that beliefs about craving and the severity of
      physical dependence may play an important role in relapse of male alcoholic
      patients. These factors could have a direct clinical application for predicting
      relapse to drinking in male alcohol-dependent patients.

PMID- 16459948
TI  - Using predictive value, sensitivity and specificity to interpret laboratory
      tests: PSA for the diagnosis of prostate cancer.
AB  - The Prostate Cancer Prevention Trial yields a means to evaluate PSA screening for
      prostate cancer detection. The receiver operating characteristic curve shows that
      PSA above 2.5 provides optimum sensitivity and specificity for prostate cancer
      diagnosis by needle biopsy. However, the maximum positive predictive value of 48%
      occurs at PSA above 4.0 and does not increase at higher PSA cutpoints.
      Consideration of test sensitivity and specificity alone is not sufficient for
      optimal interpretation of test results.

PMID- 16459949
TI  - Mortality derived from 5-year survival in patients with Alzheimer disease.
AB  - OBJECTIVE: The objective of the authors of the source article was to investigate
      survival and course of the disease in a registry of patients with Alzheimer
      disease diagnosed from 1987-1996. The objective of this article is to derive
      expected mortality, age/sex-matched as closely as possible to data available in
      the article, and to derive comparative mortality from the survival results at 5
      years. METHODS: The cohort of 521 patients with newly recognized senile dementia
      (Alzheimer disease) was drawn from a health organization in western Washington
      with an enrollment of 23,000 members age 60 years and older. After initial
      selection, a careful evaluation was made to confirm the diagnosis. The cohort was
      followed to death or 2001, with follow-up (FU) ranging from 0.2 to 14 years (mean
      5.2 years). The authors used elaborate statistical methods in their analysis of
      results. A detailed description is given in the text of this article on the
      derivation of both observed and expected mean annual mortality rates to obtain
      excess death rates (EDR) and mortality ratios (MR) as indices of excess mortality
      averaged over 5 years of FU. RESULTS: All patients were age 60 or older, mean age
      was 80.2 years, and females outnumbered males, 66% to 34%. The overall EDR, all
      patients combined, was 37 extra deaths per 1000 per year. For all males EDR was
      52; and for all females, EDR was 33 per 1000 per year. The corresponding MR
      values were 142%, 149% and 141%. EDR and MR increased with test scores measuring
      severity of cognitive impairment, with physical features of the severity of the
      dementia, and especially with the presence of comorbid diseases such as stroke,
      coronary heart disease (CHD) and congestive heart failure (CHF). With a mean age
      of 80 years, MR values are relatively low in comparison with EDR, owing to the
      high mean expected mortality. CONCLUSION: An approximate pattern of increased
      mortality has been found in a cohort of senile dementia patients in the Group
      Health Cooperative, in the area of Seattle, Washington, despite some uncertainty
      attributable to absence of sex and race distribution data within each of the 4
      individual age groups.

PMID- 16459950
TI  - Obstructive sleep apnea and cardiovascular disease and mortality: the argument
      for causality.
AB  - There is solid evidence linking obstructive sleep apnea (OSA) to cardiovascular
      mortality. Although it has yet to be scientifically proven that OSA causes
      cardiovascular disease, many investigators consider it an independent
      cardiovascular risk factor. Its impact on the cardiovascular mortality risk of a
      given applicant varies depending upon the severity of the condition, compliance
      with treatment, and the applicant's specific cardiovascular milieu. This review
      is aimed at making mortality risk assessment more accurate by describing what is
      known of the physiologic mechanisms by which OSA may influence cardiovascular
      mortality and providing an appreciation for the magnitude of this risk. In doing
      so, an argument supporting OSA as a cause for cardiovascular disease and
      mortality emerges.

PMID- 16459951
TI  - Sarcoidosis: a review.
AB  - Sarcoidosis is a systemic inflammatory disorder characterized by non-caseating
      granulomas found in the lung, lymphatic systems, and potentially in a host of
      other tissues and organs. Despite intriguing hints of infectious or environmental
      etiology, causation remains a mystery. The diagnosis, therefore, requires
      demonstration of granulomatous inflammation in more than one organ and exclusion
      of any of the known causes of granulomatous disease or local sarcoid reaction.
      Clinicians and underwriters alike frequently forget the latter requirement. For
      this reason, the other causes of granulomatous inflammation will be included in
      this treatise. Although the vast majority of applicants with sarcoidosis exhibit
      limited or remitting disease, the remaining applicants represent increased risk
      of both morbidity and mortality. This paper reviews the relevant clinical,
      radiographic, and laboratory findings that may help identify those applicants
      with increased or prohibitive risk for life or disability insurance.

PMID- 16459952
TI  - The medical officer's role in critical illness insurance product development.
AB  - Critical illness insurance is a new (to the US), medically sophisticated
      insurance product that is tantalizing some US insurers. Few have brought a
      product to market, but many opine that a US breakthrough is in the offing. Would
      you rise to the challenge and craft an opportunity to participate in the
      development of a new product concept? How do medical officers bring value to the
      product development world? Do medical officers belong in the domain of product
      actuaries and consultants who bring new product ideas to life? Dr. Jan von
      Overbeck and I presented a workshop at the 2004 AAIM meeting to discuss the role
      of the medical officer in the development and evaluation of critical illness
      insurance. This article summarizes that discussion for the Journal's readers.

PMID- 16459953
TI  - PubMed: a brief tutorial for physicians.
AB  - This article provides a brief overview of PubMed, an Internet search engine for
      peer reviewed medical literature. The examples illustrated here are designed for
      the life insurance medical director, but the examples can be easily modified for
      other literature searches commonly used by physicians, eg, diagnosis or
      treatment.

PMID- 16459954
TI  - Sleep apnea.

PMID- 16459955
TI  - Right atrial abnormality.
AB  - Occasionally, a prominent P wave is encountered in a life insurance applicant's
      electrocardiogram. Prominent P waves may be normal variants or alert the medical
      director to prognostically significant structural heart or pulmonary disease.
      This case study reviews the commonly used criteria for the ECG pattern of right
      atrial abnormality and some of the pitfalls associated with its use.

PMID- 16459956
TI  - Unusual QRS deflections--is this a ratable finding?--Revisited.

PMID- 16459957
TI  - Poor R wave progression revisited.

PMID- 16459958
TI  - Cranial artery dissection.
AB  - Stroke is a very common cause for mortality and morbidity, especially in the
      elderly where the cause is usually generalized arteriosclerosis. In persons less
      than 45 years of age with stroke, there is a group of uncommon illnesses that are
      often identified. This includes cranial artery dissection, accounting for
      approximately 20% of these acute neurological events. Cranial artery dissection
      can involve the carotids or vertebral system, and symptoms can be quite diverse
      depending on the area of brain ischemia. Anticoagulation is the usual treatment,
      and overall there is a good long-term prognosis from this entity.

PMID- 16459959
TI  - The dawn of evidence--based long term care risk assessment.

PMID- 16459960
TI  - Dermatomyositis.

PMID- 16459961
TI  - On a historical note: Meniere's disease.

PMID- 16459962
TI  - Trust debts put PFI plans in crisis.

PMID- 16459965
TI  - Does nursing discriminate against men?

PMID- 16459966
TI  - The nurses who shaped nursing.

PMID- 16459967
TI  - Examining the effectiveness of the nurse consultant role.
AB  - The role of nurse consultant aims to strengthen leadership and to help retain
      experienced and expert nurses in clinical practice. This article suggests that
      the consultant role is an example of how a redesigned nursing role can benefit
      patient care and service provision.

PMID- 16459968
TI  - Septic shock.

PMID- 16459969
TI  - Assessment of consciousness. Part one.

PMID- 16459970
TI  - Challenges in nursing adults with congenital heart disease.
AB  - Heart failure is a growing problem and is commonly associated with an older
      population. A proportion of young people also have heart failure. These patients
      are quite rarely seen but are increasing in number, and heart failure nurses need
      to ensure that when these patients present in clinic they have an understanding
      of their differing needs in comparison with older cardiac patients.

PMID- 16459971
TI  - Glyceryl trinitrate.

PMID- 16459972
TI  - Facilitating practice learning through a clinical academy.
AB  - This article reports on a project that identified a range of solutions to the
      challenges of facilitating induction and mandatory training within an acute
      general hospital. This involved developing a 'blended' approach to delivering
      induction and mandatory training/education.

PMID- 16459973
TI  - Should health care assistants apply compression bandages?
AB  - In 2004 the Leg Ulcer Forum issued a consensus statement, which stipulated that
      health care assistants should not apply compression bandaging. Because concerns
      have been raised about the role of unqualified staff in general wound management,
      the forum's executive has reissued the statement.

PMID- 16459974
TI  - Managing diabetes in primary care. Interview by Nicola O'Connell.

PMID- 16459989
TI  - Neurofibromatosis-associated nerve sheath tumors. Case report and review of the
      literature.
AB  - In this paper the authors describe a patient with neurofibromatosis Type 1 (NF1)
      who presented with sequelae of this disease. They also review the current
      literature on NF1 and NF2 published between 2001 and 2005. The method used to
      obtain information for the case report consisted of a family member interview and
      a review of the patient's chart. For the literature review the authors used the
      search engine Ovid Medline to identify papers published on the topic between 2001
      and 2005. Neurofibromatosis Type 1 appears in approximately one in 2500 to 4000
      births, is caused by a defect on 17q11.2, and results in neurofibromin
      inactivation. The authors reviewed the current literature with regard to the
      following aspects of this disease: 1) diagnostic criteria for NF1; 2) criteria
      for other NF1-associated manifestations; 3) malignant peripheral nerve sheath
      tumors (PNSTs); 4) the examination protocol for a patient with an NF1-related
      NST; 5) imaging findings in patients with NF1; 6) other diagnostic studies; 7)
      surgical and adjuvant treatment for NSTs and malignant PNSTs; and 8) hormone
      receptors in NF1-related tumors. Pertinent illustrations are included.
      Neurofibromatosis Type 2 occurs much less frequently than NF1, that is, in one in
      33,000 births. Mutations in NF2 occur on 22q12 and result in inactivation of the
      tumor suppressor merlin. The following data on this disease are presented: 1)
      diagnostic criteria for NF2; 2) criteria for other NF2 manifestations; 3)
      malignant PNSTs in patients with NF2; 4) examination protocol for the patient
      with NF2 who has an NST; and 5) imaging findings in patients with NF2. Relevant
      illustrations are included. It is important that neurosurgeons be aware of the
      sequelae of NF1 and NF2, because they may be called on to treat these conditions.

PMID- 16459990
TI  - Genetics of choroid plexus tumors.
AB  - Choroid plexus tumors consist of papillomas and carcinomas. A variety of germline
      and somatic genetic changes have been demonstrated for each of these subtypes. In
      this paper, the authors summarize the current knowledge of the genetic bases of
      these tumors.

PMID- 16459991
TI  - Molecular genetics of atypical teratoid/rhabdoid tumor.
AB  - Rhabdoid tumors are extremely aggressive malignancies that generally occur in
      infants and young children. The most common locations are the kidney and central
      nervous system (atypical teratoid/rhabdoid tumor [RT]), although RTs can also
      arise in most soft-tissue sites. Rhabdoid tumors in all anatomical locations have
      a similar molecular origin. Mutation or deletion of both copies of the hSNF5/INI1
      gene that maps to chromosome band 22q11.2 is observed in approximately 70% of
      primary tumors. An additional 20 to 25% of tumors have reduced expression at the
      RNA or protein level, indicative of a loss-of-function event. The INI1 protein is
      a component of the SWI/SNF chromatin remodeling complex. The complex is recruited
      to promoters of a large variety of genes involved in cell signaling, growth, and
      differentiation. This review summarizes what is currently known regarding the
      molecular genetics of RTs.

PMID- 16459992
TI  - Neurosurgical implications of neurofibromatosis Type I in children.
AB  - Neurofibromatosis Type 1 (NF1) is one of the most common inherited diseases in
      humans. It is caused by a mutation in the NF1 gene on chromosome 17, and is
      associated with numerous central and peripheral nervous system manifestations.
      Children with NF1 are at high risk of harboring numerous lesions that may require
      the attention of a neurosurgeon. Some of these include optic nerve gliomas,
      hydrocephalus, intraspinal tumors, and peripheral nerve tumors. Although most of
      the neoplasms that affect the brain, spine, and peripheral nerves of children are
      low-grade lesions, there is a small but real risk that some of these lesions may
      become high grade over time, requiring other forms of therapy than surgery alone.
      Other associated disorders that may result from NF1 in childhood include Chiari
      malformation Type I, scoliosis, and pulsating exophthalmos from the absence of
      the sphenoid wing. In this review, the major lesions that are found in children
      with NF1 are reviewed as well as the types of treatment that are offered by
      neurosurgeons and other members of the treating team. Today, optimum care of the
      child with NF1 is provided by a multidisciplinary team comprising neurosurgeons,
      neurologists, ophthalmologists, radiologists, orthopedic surgeons, and plastic
      surgeons.

PMID- 16459993
TI  - Tuberous sclerosis: a syndrome of incomplete tumor suppression.
AB  - Tuberous sclerosis (TS) is a congenital neurocutaneous syndrome (or phacomatosis)
      characterized by widespread development of hamartomas in multiple organs. For
      affected individuals, neurological and psychiatric complications are the most
      disabling and lethal features. Although the clinical phenotype of TS is complex,
      only three lesions characterize the neuropathological features of the disease:
      cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas.
      The latter is a benign brain tumor of mixed neuronal and glial origin. Tuberous
      sclerosis is caused by loss-of-function mutations in one of two genes, TSC1 or
      TSC2. The normal cellular proteins encoded by these genes, hamartin and tuberin,
      respectively, form a heterodimer that suppresses cell growth in the central
      nervous system by dampening the phosphatidylinositol 3-kinase signal transduction
      pathway. The authors review the clinical and neuropathological features of TS as
      well as recent research into the molecular biology of this disease. Through this
      work, investigators are beginning to resolve the paradoxical findings that
      malignant cancers seldom arise in patients with TS, even though the signaling
      molecules involved are key mediators of cancer cell growth.

PMID- 16459994
TI  - Tuberous sclerosis complex: molecular pathogenesis and animal models.
AB  - Mutations in one of two genes, TSC1 and TSC2, result in a similar disease
      phenotype by disrupting the normal interaction of their protein products,
      hamartin and tuberin, which form a functional signaling complex. Disruption of
      these genes in the brain results in abnormal cellular differentiation, migration,
      and proliferation, giving rise to the characteristic brain lesions of tuberous
      sclerosis complex (TSC) called cortical tubers. The most devastating
      complications of TSC affect the central nervous system and include epilepsy,
      mental retardation, autism, and glial tumors. Relevant animal models, including
      conventional and conditional knockout mice, are valuable tools for studying the
      normal functions of tuberin and hamartin and the way in which disruption of their
      expression gives rise to the variety of clinical features that characterize TSC.
      In the future, these animals will be invaluable preclinical models for the
      development of highly specific and efficacious treatments for children affected
      with TSC.

PMID- 16459995
TI  - Imaging characteristics and growth of subependymal giant cell astrocytomas.
AB  - OBJECT: Subependymal giant cell astrocytomas (SEGAs) are a common manifestation
      of tuberous sclerosis (TS). These evolving tumors have a propensity to cause
      obstructive hydrocephalus, usually due to obstruction at the level of the foramen
      of Monro. Differentiating SEGAs from subependymal nodules (SENs) before
      obstruction occurs may improve the morbidity associated with these tumors. In
      this study the authors' aim was to determine imaging characteristics of proven
      tumors in a single-center pediatric population. METHODS: The authors
      retrospectively reviewed all records and images obtained in patients with TS in
      whom results of biopsy sampling had proven that their tumors were SEGAs. Time to
      presentation, signs and symptoms at presentation, and imaging characteristics of
      the evolving tumors were noted. Twelve patients with 14 SEGAs proven by the
      results of biopsy sampling were reviewed. Resection was recommended for
      symptomatic and neuroimaging evidence of hydrocephalus (41%), tumor growth
      without evidence of hydrocephalus (33%), and for poorly controlled seizures
      (25%). The mean diameter of the tumors at the time of resection was 1.9 cm (range
      0.3-4 cm), and no tumor recurred. Because of the pathological and radiographic
      continuum of SENs and SEGAs, it remains difficult to predict whether and when a
      given lesion will progress. Tumor growth and contrast enhancement are the most
      common signs of progression on neuroimages, and may be seen prior to the
      development of obstructive hydrocephalus. CONCLUSIONS: Patients with SENs and
      SEGAs should undergo follow-up neuroimaging at yearly intervals, and if lesions
      show signs of progression (contrast enhancement or growth), these intervals
      should be shortened and consideration given to early resection.

PMID- 16459996
TI  - Cowden disease and Lhermitte-Duclos disease: an update. Case report and review of
      the literature.
AB  - OBJECT: Cowden disease is a rare autosomal-dominant phacomatosis and cancer
      syndrome that is associated with Lhermitte-Duclos disease (LDD), also called
      dysplastic cerebellar gangliocytoma. METHODS: In this review the authors
      summarize the additions to the literature during the past 5 years, with emphasis
      on new case reports and advances in imaging and molecular biology. Adult-onset
      LDD is now considered pathognomonic for Cowden disease. Approximately 220 cases
      of LDD have been reported. Magnetic resonance imaging in patients with LDD is
      often diagnostic, and imaging studies have facilitated accurate diagnosis and
      contributed to the improved outcome in affected patients. Cowden disease and
      other rare, related disorders, such as Bannayan-Riley-Ruvalcaba, Proteus, and
      Proteus- like syndromes, are often caused by mutations of the PTEN gene.
      CONCLUSIONS: Because of the high incidence of systemic cancer in patients with
      Cowden disease, it is important for neurosurgeons to recognize the association
      between this disease and LDD and to refer affected patients for appropriate
      cancer screenings and interventions.

PMID- 16459997
TI  - Focal cortical dysplasia: a review of pathological features, genetics, and
      surgical outcome.
AB  - Focal cortical dysplasia (FCD) is found in approximately one-half of patients
      with medically refractory epilepsy. These lesions may involve only mild
      disorganization of the cortex, but they may also contain abnormal neuronal
      elements such as balloon cells. Advances in neuroimaging have allowed better
      identification of these lesions, and thus more patients have become surgical
      candidates. Molecular biology techniques have been used to explore the genetics
      and pathophysiological characteristics of FCD. Data from surgical series have
      shown that surgery often results in significant reduction or cessation of
      seizures, especially if the entire lesion is resected.

PMID- 16459998
TI  - Familial intracranial ependymomas. Report of three cases in a family and review
      of the literature.
AB  - Familial cases of intracranial ependymomas have been well documented in the
      literature. The authors present two cases from a family in which three members
      harbored intracranial ependymomas. A 54-year-old man with fourth ventricular
      ependymoma underwent resection of the tumor followed by radiation therapy. His
      son presented at age 36 years with a fourth ventricular tanycytic ependymoma and
      underwent total resection of the ependymoma with postoperative radiation therapy.
      The father's sister had been treated at another institution for a posterior fossa
      ependymoma.The association of ependymomas with molecular genetic alterations in
      chromosome 22 has been previously described. Further investigation of the genetic
      influences may lead to better therapeutic approaches for this relatively rare
      clinicopathological entity.

PMID- 16459999
TI  - A novel minimally invasive presacral approach and instrumentation technique for
      anterior L5-S1 intervertebral discectomy and fusion: technical description and
      case presentations.
AB  - OBJECT: The authors describe a new paracoccygeal approach to the L5-S1 junction
      for interbody fusion with transsacral instrumentation. The purpose of this
      technical note is to demonstrate a novel surgical approach, technique, and
      instrumentation system for the treatment of L5-S1 instability in degenerative
      disc disease and spondylolisthesis. METHODS: This technical note highlights the
      AxiaLif (TranS1) transsacral system as an alternative method to transforaminal
      lumbar interbody fusion or posterior lumbar interbody fusion. Via a novel
      presacral approach corridor, a truly percutaneous L5-S1 discectomy, interbody
      distraction, and fixation are achieved, and retroperitoneal viscera and dorsal
      neural elements are avoided. Percutaneous pedicle screw fixation is then used to
      provide additional stabilization at the treated level. CONCLUSIONS: This novel
      technique of interbody distraction and fusion via a truly percutaneous approach
      corridor allows for circumferential treatment of the lower lumbar segments with
      minimal risk to the anterior organs and dorsal neural elements.

PMID- 16460001
TI  - Tyrosine 387 and arginine 404 are critical in the hydrolytic mechanism of
      Escherichia coli aminopeptidase P.
AB  - Analysis of the pH-rate profile for catalysis of bradykinin cleavage by
      aminopeptidase P (AMPP), a manganese-containing hydrolase from Escherichia coli,
      was carried out to show that optimal catalytic function is obtained at neutral
      pH. On the basis of information derived from the crystal structure, peptidase
      sequence alignments, and the hydrolysis of organophosphate triesters, active site
      residues Arg153, Arg370, Trp88, Tyr387, and Arg404 were identified as potential
      catalytic residues. Site-directed mutagenesis was used to substitute these
      residues with Leu, Ala, Trp, Lys, or Phe. The kcat values for the Arg153, Arg370,
      and Trp88 mutants were nearly the same as that for the wild-type enzyme. The kcat
      values of the R404K, R404A, and Y387A mutants were lower by factors of 285, 400,
      and 16, respectively. Inductively coupled plasma mass spectrometry and circular
      dichroism spectroscopy showed that Arg404 is not required for metal chelation or
      stabilization of protein secondary structure. The hydrogen bond network observed
      between the side chains of conserved residues Asp260, Arg404, and Tyr387
      indicated that Arg404 participates in proton relay. This was further evidenced by
      the return of activity in the R404A mutant by the addition of guanidine. Also,
      reduced catalytic efficiency in the R404K mutant, which conserves the positive
      charge at the bridge site, shows that only the arginine group of Arg404 (not the
      ammonium group of Lys404) can participate in the hydrogen bond network. The
      hydrogen bond interaction between the Arg404 and the Tyr387 ring hydroxyl group
      is suggested by the reduced catalytic efficiency of the Y387F mutant.

PMID- 16460002
TI  - Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis,
      snapshots of the enzyme in action.
AB  - Pantothenate synthetase (PS) from Mycobacterium tuberculosis represents a
      potential target for antituberculosis drugs. PS catalyzes the ATP-dependent
      condensation of pantoate and beta-alanine to form pantothenate. Previously, we
      determined the crystal structure of PS from M. tuberculosis and its complexes
      with AMPCPP, pantoate, and pantoyl adenylate. Here, we describe the crystal
      structure of this enzyme complexed with AMP and its last substrate, beta-alanine,
      and show that the phosphate group of AMP serves as an anchor for the binding of
      beta-alanine. This structure confirms that binding of beta-alanine in the active
      site cavity can occur only after formation of the pantoyl adenylate intermediate.
      A new crystal form was also obtained; it displays the flexible wall of the active
      site cavity in a conformation incapable of binding pantoate. Soaking of this
      crystal form with ATP and pantoate gives a fully occupied complex of PS with ATP.
      Crystal structures of these complexes with substrates, the reaction intermediate,
      and the reaction product AMP provide a step-by-step view of the PS-catalyzed
      reaction. A detailed reaction mechanism and its implications for inhibitor design
      are discussed.

PMID- 16460000
TI  - Activity screening of carrier domains within nonribosomal peptide synthetases
      using complex substrate mixtures and large molecule mass spectrometry.
AB  - For screening a pool of potential substrates that load carrier domains found in
      nonribosomal peptide synthetases, large molecule mass spectrometry is shown to be
      a new, unbiased assay. Combining the high resolving power of Fourier transform
      mass spectrometry with the ability of adenylation domains to select their own
      substrates, the mass change that takes place upon formation of a covalent
      intermediate thus identifies the substrate. This assay has an advantage over
      traditional radiochemical assays in that many substrates, the substrate pool, can
      be screened simultaneously. Using proteins on the nikkomycin, clorobiocin,
      coumermycin A1, yersiniabactin, pyochelin, and enterobactin biosynthetic pathways
      as proof of principle, preferred substrates are readily identified from substrate
      pools. Furthermore, this assay can be used to provide insight into the timing of
      tailoring events of biosynthetic pathways as demonstrated using the bromination
      reaction found on the jamaicamide biosynthetic pathway. Finally, this assay can
      provide insight into the role and function of orphan gene clusters for which the
      encoded natural product is unknown. This is demonstrated by identifying the
      substrates for two NRPS modules from the pksN and pksJ genes that are found on an
      orphan NRPS/PKS hybrid cluster from Bacillus subtilis. This new assay format is
      especially timely for activity screening in an era when new types of thiotemplate
      assembly lines that defy classification are being discovered at an accelerating
      rate.

PMID- 16460003
TI  - Crystal structure of mouse succinic semialdehyde reductase AKR7A5: structural
      basis for substrate specificity.
AB  - The aldo-keto reductases make up a superfamily of enzymes which can reduce a
      variety of aldehydes and ketones to their corresponding alcohols. Within each
      family are distinct preferences for certain substrates, presumably reflecting
      their role within the cell. The original member of the AKR7A subfamily was
      purified from liver as an aflatoxin dialdehyde reductase AKR7A1. However, recent
      additions to the family have revealed that even closely related enzymes have
      clear substrate preferences with AKR7A2, AKR7A4, and AKR7A5 showing much higher
      affinities for succinic semialdehyde (SSA) than does AKR7A1. To investigate the
      structural basis of this specificity, the crystal structure of mouse AKR7A5 has
      been determined to better than 2.5 A resolution. The structure is of the ternary
      complex of the enzyme with NADP+ and tartrate as an inhibitor. This structure has
      the same overall fold as the previously determined structure of AKR7A1; however,
      there are a number of differences in loops around the active site that contribute
      to observed differences in the substrate specificity between the AKR7A enzymes.
      Several differences are the result of bulky hydrophobic residues found in AKR7A5,
      namely, Met44, Trp77, and Trp224, which significantly restrict the size and
      modify the architecture of the substrate-binding pocket, producing a tighter or
      less flexible binding site for SSA than in AKR7A1. Site-directed mutagenesis was
      used to introduce Met44, Trp77, and Trp224 individually into AKR7A1, to test if
      they improved the affinity of the enzyme for SSA. Each mutation showed improved
      affinity for SSA, with Trp77Met having the largest effect. This confirms the role
      of these amino acids as substrate determinants for SSA.

PMID- 16460004
TI  - Engineering artificially split inteins for applications in protein chemistry:
      biochemical characterization of the split Ssp DnaB intein and comparison to the
      split Sce VMA intein.
AB  - In protein trans-splicing, an intein domain split into two polypeptide chains
      mediates linkage of the flanking amino acid sequences, the N- and C-terminal
      exteins, with a native peptide bond. This process can be exploited to assemble
      proteins from two separately prepared fragments, e.g., for the segmental labeling
      with isotopes for NMR studies or the incorporation of chemical and biophysical
      probes. Split inteins can be artificially generated by genetic means; however,
      the purified inteinN and inteinC fragments usually require a denaturation and
      renaturation treatment to fold into the active intein, thus preventing their
      application to proteins that cannot be refolded. Here, we report that the
      purified fragments of the artificially split DnaB helicase of Synechocystis spp.
      PCC6803 (Ssp DnaB) intein are active under native conditions. The first-order
      rate constant of the protein trans-splicing reaction was 7.1 x 10(-4) s(-1). The
      previously described split vacuolar ATPase of Saccharomyces cerevisiae (Sce VMA)
      intein is the only other artificially split intein that is active under native
      conditions; however, it requires induced complex formation of the intein
      fragments by auxiliary dimerization domains for efficient protein trans-splicing.
      In contrast, fusion of the dimerization domains to the split Ssp DnaB intein
      fragments had no effect on activity. This difference was also reflected by a
      higher thermostability of the split Ssp DnaB intein. Further investigations of
      the split Sce VMA intein under optimized conditions revealed a first-order rate
      constant of 9.4 x 10(-4) s(-1) for protein trans-splicing and 1.7 x 10(-3) s(-1)
      for C-terminal cleavage involving a Cys1Ala mutant. Finally, we show that the two
      split inteins are orthogonal, suggesting further applications for the assembly of
      proteins from more than two parts.

PMID- 16460006
TI  - Chromatin compaction at the mononucleosome level.
AB  - Using a previously described FRET technique, we measured the distance between the
      ends of DNA fragments on which nucleosomes were reconstituted from recombinant
      and native histones. This distance was analyzed in its dependence on the DNA
      fragment length, concentration of mono- and divalent counterions, presence of
      linker histone H1, and histone modifications. We found that the linker DNA arms
      do not cross under all conditions studied but diverge slightly as they leave the
      histone core surface. Histone H1 leads to a global approach of the linker DNA
      arms, confirming the notion of a "stem structure". Increasing salt concentration
      also leads to an approach of the linker DNAs. To study the effect of acetylation,
      we compared chemically acetylated recombinant histones with histones prepared
      from HeLa cells, characterizing the sites of acetylation by mass spectroscopy.
      Nucleosomes from chemically acetylated histones have few modifications in the
      core domain and form nucleosomes normally. Acetylating all histones or
      selectively only H3 causes an opening of the nucleosome structure, indicated by
      the larger distances between the linker DNA ends. Selective acetylation of H4
      distances the linker ends for short fragments but causes them to approach each
      other for fragments longer than 180 bp.

PMID- 16460007
TI  - Disulfide formation and stability of a cysteine-rich repeat protein from
      Helicobacter pylori.
AB  - Helicobacter pylori cysteine-rich proteins (Hcps) are disulfide-containing repeat
      proteins. The repeating unit is a 36-residue, disulfide-bridged, helix-loop-helix
      motif. We use the protein HcpB, which has four repeats and four disulfide bridges
      arrayed in tandem, as a model to determine the thermodynamic stability of a
      disulfide-rich repeat protein and to study the formation and the contribution to
      stability of the disulfide bonds. When the disulfide bonds are intact, the
      chemical unfolding of HcpB at pH 5 is cooperative and can be described by a two
      state reaction. Thermal unfolding is reversible between pH 2 and 5 and
      irreversible at higher pH 5. Differential scanning calorimetry shows
      noncooperative structural changes preceding the main thermal unfolding
      transition. Unfolding of the oxidized protein is not an all-or-none two-state
      process, and the disulfide bonds prevent complete unfolding of the polypeptide
      chain. The reduced protein is significantly less stable and does not unfold in a
      cooperative way. During oxidative refolding of the fully reduced protein, all the
      possible disulfide intermediates with a correct disulfide bond are formed.
      Formation of "wrong" (non-native) disulfide bonds could not be demonstrated,
      indicating that the reduced protein already has some partial repeating structure.
      There is a major folding intermediate with disulfides in the second, third, and
      fourth repeat and reduced cysteines in the first repeat. Disulfide formation in
      the first repeat limits the overall rate of oxidative refolding and contributes
      about half of the thermodynamic stability to native HcpB, estimated as 27 kJ mol(
      1) at 25 degrees C and pH 7. The high contribution to stability of the first
      repeat may be explained by the repeat acting as a cap to protect the hydrophobic
      interior of the molecule.

PMID- 16460005
TI  - Structure, function, and wavelength selection in blue-absorbing proteorhodopsin.
AB  - The absorption maximum of blue proteorhodopsin (BPR) is the most blue-shifted of
      all retinal proteins found in archaea or bacteria, with the exception of sensory
      rhodopsin II (SRII). The absorption spectrum also exhibits a pH dependence larger
      than any other retinal protein. We examine the structural origins of these two
      properties of BPR by using optical spectroscopy, homology modeling, and molecular
      orbital theory. Bacteriorhodopsin (BR) and SRII are used as homology parents for
      comparative purposes. We find that the tertiary structure of BPR based on SRII is
      more realistic with respect to free energy, dynamic stability, and spectroscopic
      properties. Molecular orbital calculations including full single- and double
      configuration interaction within the chromophore pi-electron system provide
      perspectives on the wavelength regulation in this protein and indicate that Arg
      95, Gln-106, Glu-143, and Asp-229 play important, and in some cases pH-dependent
      roles. A possible model for the 0.22 eV red shift of BPR at low pH is examined,
      in which Glu-143 becomes protonated and releases Arg-95 to rotate up into the
      binding site, altering the electrostatic environment of the chromophore. At high
      pH, BPR has spectroscopic properties similar to SRII, but at low pH, BPR has
      spectroscopic properties more similar to BR. Nevertheless, SRII is a
      significantly better homology model for BPR and opens up the question of whether
      this protein serves as a proton pump, as commonly believed, or is a light sensor
      with structure-function properties more comparable to those of SRII. The function
      of BPR in the native organism is discussed with reference to the results of the
      homology model.

PMID- 16460009
TI  - Biochemical properties of UspG, a universal stress protein of Escherichia coli.
AB  - Universal stress proteins (USPs) are abundant and widely distributed proteins.
      Even so, their mode of function is hardly understood. This study focuses on UspG
      (UP12) of Escherichia coli, which belongs to the UspFG subfamily. Resolution of
      UspG by two-dimensional gel electrophoresis uncovered a posttranslational
      modification during its overexpression in E. coli. One isoform represented the
      adenylated/phosphorylated state of UspG. In vitro experiments with His-tagged
      UspG revealed intrinsic autophosphorylation and autoadenylation activity.
      Moreover, covalently bound AMP could be released from UspG by piperidine
      treatment and subsequent thin-layer chromatography. UspG was characterized as a
      dimer, a property that got lost in a C-terminal truncated UspG. Moreover, the C
      terminal part was found to be important for structural stability, because the
      truncation of six C-terminal amino acids resulted in a protein that was further
      truncated by 18 amino acids in vivo. The truncated UspG was still enzymatically
      active, albeit the activities were significantly reduced.

PMID- 16460008
TI  - Unfolding, aggregation, and amyloid formation by the tetramerization domain from
      mutant p53 associated with lung cancer.
AB  - The p53 tumor suppressor is a tetrameric transcriptional enhancer, and its
      activity is compromised by mutations that cause amino acid substitutions in its
      tetramerization domain. Here we analyze the biochemical and biophysical
      properties of peptides corresponding to amino acids 319-358 of wild-type human
      p53, which includes the tetramerization domain, and that of a cancer-derived
      mutant with valine substituted for glycine 334. Unlike the wild-type peptide, the
      G334V peptide forms amyloid fibrils by a two-step process under physiological
      conditions of temperature and pH. Nevertheless, the G334V peptide is capable of
      forming heterooligomers with a wild-type peptide. Computational modeling of the
      G334V peptide structure suggests that substitution of valine for glycine 334
      causes a local distortion that contributes to a beta-dominated structural
      transition leading to amyloid formation. Since the distortion is mostly on the
      surface, the mutant peptide is still able to form a pseudonative tetramer complex
      at higher concentrations and/or lower temperatures. Our study suggests a new
      potential mechanism by which mutations that compromise tetramer formation
      inactivate p53 as a tumor suppressor.

PMID- 16460010
TI  - Analysis of ligand binding and protein dynamics of human retinoid X receptor
      alpha ligand-binding domain by nuclear magnetic resonance.
AB  - Retinoid X receptors (RXRs) are nuclear receptors that can activate transcription
      as homodimers or as obligate heterodimeric partners of other nuclear receptors.
      While the crystal structures of the RXR ligand-binding domains (LBD) have been
      previously determined, the dynamics of activation is less well characterized at
      an atomic level. To probe the effect of ligand binding on RXR LBD dynamics, we
      initiated nuclear magnetic resonance studies of recombinant human RXRalpha LBD
      (T223-T462) with and without bound 9-cis-retinoic acid (9cRA). The 1HN, 15N,
      13C(alpha), 13CO, and 13C(beta) resonance assignments were established for 164 of
      240 residues in apo-RXRalpha LBD. Resonances corresponding to an additional 47
      residues emerged upon 9cRA binding. These additional residues included those
      located in the vicinity of the ligand-binding pocket (helices H3, H5, and strands
      S1, S2), as well as residues located at the dimerization interface (helices H9
      and H10). Thus 9cRA binding stabilized the ligand-binding pocket and had
      allosteric effects on the dimerization interface. Ligand-induced chemical shift
      perturbations outside the binding cavity were mapped to helix H3 and the AF-2
      helix H12, indicating conformational changes in these regions. However, helix
      H11, a component of the tetramerization interface, and a large part of helix H10,
      a component of the dimerization interface, remained undetectable even after 9cRA
      binding. Although apo- and holo-hRXRalpha LBD existed predominantly as homodimers
      in solution, exchange between monomeric, dimeric, and tetrameric forms of the
      protein could have contributed to line broadening of cross-peaks corresponding to
      helices H10 and H11. 15N T1, T2, and steady-state {1H}-15N NOE data collected at
      500 and 700 MHz static magnetic fields showed that the internal motions for the
      residues in the H1-H3 loop (K245-D263) were much less restricted than those in
      the protein core for both apo- and holo-forms. Significant exchange R(ex)
      contributions to the transverse relaxation rate were detected for most of the
      residues measured in both apo- and holo-RXRalpha LBDs by transverse relaxation
      optimized spectroscopy-Carr-Purcell-Meiboom-Gill (CPMG) experiments at two B1
      field strengths. Taken together these results suggest that the RXRalpha LBD
      exists as a dynamic ensemble of conformations, even after binding its cognate
      ligand. Such dynamic characteristics may allow RXRalpha to partner with multiple
      nuclear receptors.

PMID- 16460011
TI  - Agonists and partial agonists of rhodopsin: retinal polyene methylation affects
      receptor activation.
AB  - Using Fourier transform infrared (FTIR) difference spectroscopy, we have studied
      the impact of sites and extent of methylation of the retinal polyene with respect
      to position and thermodynamic parameters of the conformational equilibrium
      between the Meta I and Meta II photoproducts of rhodopsin. Deletion of methyl
      groups to form 9-demethyl and 13-demethyl analogues, as well as addition of a
      methyl group at C10 or C12, shifted the Meta I/Meta II equilibrium toward Meta I,
      such that the retinal analogues behaved like partial agonists. This equilibrium
      shift resulted from an apparent reduction of the entropy gain of the transition
      of up to 65%, which was only partially offset by a concomitant reduction of the
      enthalpy increase. The analogues produced Meta II photoproducts with relatively
      small alterations, while their Meta I states were significantly altered, which
      accounted for the aberrant transitions to Meta II. Addition of a methyl group at
      C14 influenced the thermodynamic parameters but had little impact on the position
      of the Meta I/Meta II equilibrium. Neutralization of the residue 134 in the E134Q
      opsin mutant increased the Meta II content of the 13-demethyl analogue, but not
      of the 9-demethyl analogue, indicating a severe impairment of the allosteric
      coupling between the conserved cytoplasmic ERY motif involved in proton uptake
      and the Schiff base/Glu 113 microdomain in the 9-demethyl analogue. The 9-methyl
      group appears therefore essential for the correct positioning of retinal to link
      protonation of the cytoplasmic motif with protonation of Glu 113 during receptor
      activation.

PMID- 16460012
TI  - Redox interaction of cytochrome c3 with [NiFe] hydrogenase from Desulfovibrio
      vulgaris Miyazaki F.
AB  - Cytochrome c3 isolated from a sulfate-reducing bacterium, Desulfovibrio vulgaris
      Miyazaki F, is a tetraheme protein. Its physiological partner, [NiFe]
      hydrogenase, catalyzes the reversible oxidoreduction of molecular hydrogen. To
      elucidate the mechanism of electron transfer between cytochrome c3 and [NiFe]
      hydrogenase, the transient complex formation by these proteins was investigated
      by means of NMR. All NH signals of uniformly 15N-labeled ferric cytochrome c3
      except N-terminus, Pro, and Gly73 were assigned. 1H-15N HSQC spectra were
      recorded for 15N-labeled ferric and ferrous cytochrome c3, in the absence and
      presence of hydrogenase. Chemical shift perturbations were observed in the region
      around heme 4 in both oxidation states. Additionally, the region between hemes 1
      and 3 in ferrous cytochrome c3 was affected in the presence of hydrogenase,
      suggesting that the mode of interaction is different in each redox state. Heme 3
      is probably the electron gate for ferrous cytochrome c3. To investigate the
      transient complex of cytochrome c3 and hydrogenase in detail, modeling of the
      complex was performed for the oxidized proteins using a docking program, ZDOCK
      2.3, and NMR data. Furthermore, the roles of lysine residues of cytochrome c3 in
      the interaction with hydrogenase were investigated by site-directed mutagenesis.
      When the lysine residues around heme 4 were replaced by an uncharged residue,
      methionine, one by one, the Km of the electron-transfer kinetics increased. The
      results showed that the positive charges of Lys60, Lys72, Lys95, and Lys101
      around heme 4 are important for formation of the transient complex with [NiFe]
      hydrogenase in the initial stage of the cytochrome c3 reduction. This finding is
      consistent with the most possible structure of the transient complex obtained by
      modeling.

PMID- 16460014
TI  - NMR studies of ligand binding to P450(eryF) provides insight into the mechanism
      of cooperativity.
AB  - Cytochrome P450's (P450's) catalyze the oxidative metabolism of most drugs and
      toxins. Although extensive studies have proven that some P450's demonstrate both
      homotropic and heterotropic cooperativity toward a number of substrates, the
      mechanistic and molecular details of P450 allostery are still not well
      established. Here, we use UV/vis and heteronuclear nuclear magnetic resonance
      (NMR) spectroscopic techniques to study the mechanism and thermodynamics of the
      binding of two 9-aminophenanthrene (9-AP) and testosterone (TST) molecules to the
      erythromycin-metabolizing bacterial P450(eryF). UV/vis absorbance spectra of
      P450(eryF) demonstrated that binding occurs with apparent negative homotropic
      cooperativity for TST and positive homotropic cooperativity for 9-AP with Hill
      equation-derived dissociation constants of K(S) = 4 and 200 microM, respectively.
      The broadening and shifting observed in the 2D-{1H,15N}-HSQC-monitored titrations
      of 15N-Phe-labeled P450(eryF) with 9-AP and TST indicated binding on intermediate
      and fast chemical exchange time scales, respectively, which was consistent with
      the Hill-equation-derived K(S) values for these two ligands. Regardless of the
      type of spectral perturbation observed (broadening for 9-AP and shifting for
      TST), the 15N-Phe NMR resonances most affected were the same in each titration,
      suggesting that the two ligands "contact" the same phenylalanines within the
      active site of P450(eryF). This finding is in agreement with X-ray crystal
      structures of bound P450(eryF) showing different ligands occupying similar active
      site niches. Complex spectral behavior was additionally observed for a small
      collection of resonances in the TST titration, interpreted as multiple binding
      modes for the low-affinity TST molecule or multiple TST-bound P450(eryF)
      conformational substates. A structural and energetic model is presented that
      combines the energetics and structural aspects of 9-AP and TST binding derived
      from these observations.

PMID- 16460013
TI  - NMR-derived dynamic aspects of N-type inactivation of a Kv channel suggest a
      transient interaction with the T1 domain.
AB  - Some eukaryotic voltage-gated K+ (Kv) channels contain an N-terminal inactivation
      peptide (IP), which mediates a fast inactivation process that limits channel
      function during membrane depolarization and thus shapes the action potential. We
      obtained sequence-specific nuclear magnetic resonance (NMR) assignments for the
      polypeptide backbone of a tetrameric N-terminal fragment (amino acids 1-181) of
      the Aplysia Kv1.1 channel. Additional NMR measurements show that the
      tetramerization domain 1 (T1) has the same globular structure in solution as
      previously determined by crystallography and that the IP (residues 1-20) and the
      linker (residues 21-65) are in a flexibly disordered, predominantly extended
      conformation. A potential contact site between the T1 domain and the flexible
      tail (residues 1-65) has been identified on the basis of chemical-shift changes
      of individual T1 domain amino acids, which map to the T1 surface near the
      interface between adjacent subunits. Paramagnetic perturbation experiments
      further indicate that, in the ensemble of solution conformers, there is at least
      a small population of species with the IP localized in close proximity to the
      proposed interacting residues of the T1 tetramer. Electrophysiological
      measurements show that all three mutations in this pocket that we tested slow the
      rate of inactivation and speed up recovery, as predicted from the preinactivation
      site model. These results suggest that specific, short-lived transient
      interactions between the T1 domain and the IP or the linker segment may play a
      role in defining the regulatory kinetics of fast channel inactivation.

PMID- 16460015
TI  - Regulation of methane monooxygenase catalysis based on size exclusion and quantum
      tunneling.
AB  - The hydroxylase component (MMOH) of the soluble form of methane monooxygenase
      (sMMO) isolated from Methylosinus trichosporium OB3b catalyzes both the O2
      activation and the CH4 oxidation reactions at the oxygen-bridged dinuclear iron
      cluster present in its buried active site. During the reaction cycle, the diiron
      cluster forms a bis-mu-oxo-(Fe(IV))2 intermediate termed compound Q (Q) that
      reacts directly with methane. Many adventitious substrates also react with Q,
      most at a relatively slow rate. We have proposed that Q reacts preferentially
      with CH4 because the sMMO regulatory component MMOB induces a size selective pore
      into the MMOH active site as the two components form a complex. Support for this
      proposal has come through the observation of a nonlinear Arrhenius plot for the
      CH4 oxidation, presumably due to a shift in rate-limiting step from substrate
      binding at low temperature to C-H bond cleavage at high temperature. Reactions of
      all substrates other than CH4 fail to exhibit a break in the Arrhenius plot
      because binding is always rate limiting in the temperature range explored. Here
      we show that it is possible to induce a break in the Arrhenius plot for the
      ethane reaction with Q by using an MMOB mutant termed DBL2 (S109A/T111A) in which
      residues at the MMOH-MMOB interface are reduced in size. We hypothesize that this
      increases the ethane binding rate and shifts the Arrhenius breakpoint into the
      observable temperature range. As a result of this shift, the kinetic and
      activation parameters of the C-H bond breaking reaction for both methane and
      ethane can be observed using the DBL2 mutant. A 2H-KIE is observed for both
      substrate oxidation reactions when using DBL2, whereas only CH4 oxidation
      exhibits an effect when using wild type MMOB, consistent with the C-H bond
      cleaving reaction becoming at least partially rate limiting for ethane. Analysis
      of the temperature dependence of the 2H-KIE for ethane and methane for reactions
      using both mutant and wild type forms of MMOB suggests that quantum tunneling
      plays a significant role in methane oxidation but not ethane oxidation.

PMID- 16460016
TI  - Effect of n-alcohols on the structure and stability of the Drosophila odorant
      binding protein LUSH.
AB  - LUSH is an odorant binding protein expressed in the olfactory organs of
      Drosophila melanogaster that is required for the detection of alcohol in adult
      flies. Here we demonstrate that, in the absence of ligand, in vitro LUSH exists
      in a partial molten globule state. The presence of short-chain n-alcohols at
      pharmacologically relevant concentrations less than 50 mM shifts the
      conformational equilibrium to a more compact state that exhibits reduced binding
      of the fluorescent dye 1-anilino-8-naphthalenesulfonic acid. Equilibrium
      unfolding studies of LUSH-alcohol complexes reveal that, for a series of short
      chain n-alcohols, each methylene group can contribute approximately 1 K cal mol(
      1) to the overall stability of the protein-alcohol complex. Using NMR
      spectroscopy, we have identified the regions of LUSH that show increased
      conformational stability on binding alcohols. These residues primarily line the
      alcohol-binding pocket. The results presented here provide a direct measure of
      the degree of stability that alcohol imparts on LUSH. These observations may
      represent a model for how ethanol can stabilize alternative protein conformations
      in alcohol-sensitive human proteins and ultimately lead to the observed changes
      in higher order function throughout the central nervous system.

PMID- 16460017
TI  - Examination of the structure, stability, and catalytic potential in the
      engineered phosphoryl carrier domain of pyruvate phosphate dikinase.
AB  - Pyruvate phosphate dikinase (PPDK) is a multidomain protein that catalyzes the
      interconversion of ATP, pyruvate, and phosphate with AMP, phosphoenolpyruvate
      (PEP), and pyrophosphate using its central domain to transport phosphoryl groups
      between two distant active sites. In this study, the mechanism by which the
      central domain moves between the two catalytic sites located on the N-terminal
      and C-terminal domains was probed by expressing this domain as an independent
      protein and measuring its structure, stability, and ability to catalyze the
      ATP/phosphate partial reaction in conjunction with the engineered N-terminal
      domain protein (residues 1-340 of the native PPDK). The encoding gene was
      engineered to express the central domain as residues 381-512 of the native PPDK.
      The central domain was purified and shown to be soluble, monomeric (13,438 Da),
      and stable (deltaG = 4.3 kcal/mol for unfolding in buffer at pH 7.0, 25 degrees
      C) and to possess native structure, as determined by multidimensional
      heteronuclear NMR analysis. The main chain structure of the central domain in
      solution aligns closely with that of the X-ray structure of native PPDK (the root
      mean-square deviation is 2.2 A). Single turnover reactions of [14C]ATP and
      phosphate, carried out in the presence of equal concentrations of central domain
      and the N-terminal domain protein, did not produce the expected products, in
      contrast to efficient product formation observed for the N-terminal central
      domain construct (residues 1-553 of the native PPDK). These results are
      interpreted as evidence that the central domain, although solvent-compatible,
      must be tethered by the flexible linkers to the N-terminal domain for the
      productive domain-domain docking required for efficient catalysis.

PMID- 16460018
TI  - The structure of the carboxyltransferase component of acetyl-coA carboxylase
      reveals a zinc-binding motif unique to the bacterial enzyme.
AB  - Acetyl-coA carboxylase (ACC) is a central metabolic enzyme that catalyzes the
      committed step in fatty acid biosynthesis: biotin-dependent conversion of acetyl
      coA to malonyl-coA. The bacterial carboxyltransferase (CT) subunit of ACC is a
      target for the design of novel therapeutics that combat severe, hospital-acquired
      infections resistant to the established classes of frontline antimicrobials.
      Here, we present the structures of the bacterial CT subunits from two prevalent
      nosocomial pathogens, Staphylococcus aureus and Escherichia coli, at a resolution
      of 2.0 and 3.0 A, respectively. Both structures reveal a small, independent zinc
      binding domain that lacks a complement in the primary sequence or structure of
      the eukaryotic homologue.

PMID- 16460019
TI  - The Deinococcus radiodurans-encoded HU protein has two DNA-binding domains.
AB  - Deinococcus radiodurans can reconstitute its genome from double-strand breaks,
      most likely due to unusually efficient DNA repair and recombination. Factors that
      may contribute to such processes include the histone-like protein HU. The D.
      radiodurans-encoded HU (DrHU), which binds preferentially to DNA recombination
      intermediates, contains a 47-amino acid extension preceding the fold
      characteristic of HU proteins. Here we use electrophoretic mobility shift assays
      and DNA footprinting to show that the DrHU N-terminal domain significantly
      modulates DNA binding. The truncated DrHU (deltaDrHU), comprising only the
      conserved DNA-binding fold, has a site size of approximately 11 bp in contrast to
      full-length DrHU which does not stably engage DNA shorter than approximately 50
      bp. Unlike wild-type DrHU, deltaDrHU distinguishes between linear DNA and DNA
      with nicks or gaps. DeltaDrHU also binds preferentially to four-way junction
      (4WJ) DNA, with half-maximal saturation of 1.4 +/- 0.4 nM compared to 20 +/- 2 nM
      for 37 bp duplex DNA. However, in contrast to full-length protein which binds the
      junction arms, deltaDrHU primarily protects the junction crossover. Evidently,
      the DrHU N-terminus changes the mode of binding to both 4WJ DNA, duplex DNA, and
      DNA with nicks or gaps, thereby resulting in DrHU binding preferentially only to
      4WJ structures. Combined with Western blots that confirm the presence of the
      extended form of DrHU in vivo, our data provide mechanistic insight into
      discrimination between 4WJ DNA and other distorted DNA constructs and suggest
      that an in vivo role of DrHU may be to stabilize DNA junctions.

PMID- 16460020
TI  - Solution structure of the first intracellular loop of prostacyclin receptor and
      implication of its interaction with the C-terminal segment of G alpha s protein.
AB  - The amino acids (residues 39-51) responsible for the interaction between the
      first intracellular loop (iLP1) of the human prostacyclin receptor (IP) and G
      alpha s protein have been identified [Zhang, L., Huang, G., Wu, J., and Ruan, K.
      H. (2005) Biochemistry 44, 11389-11401]. To further characterize the
      structural/functional relationship of the iLP1 in coupling with the G alpha s
      protein, the solution structures of a constrained peptide (IP iLP1) that mimicked
      the iLP1 of the IP receptor in the absence and presence of a synthetic peptide,
      corresponding to the C-terminal 11 residues (Q384-L394 in the protein sequence)
      of the G alpha s protein (G alpha s-Ct), were determined by 2D 1H NMR
      spectroscopy. The NMR solution structural model of the iLP1 domain showed two
      turn structures in residues Arg41-Ala44 and Arg45-Phe49 with the conserved Arg45
      at the center. The conformational change of the side chain of the Arg45 was
      observed upon the addition of the G alpha s-Ct peptide. On the other hand, the
      solution structural models of the G alpha s-Ct peptide in the absence and
      presence of the IP iLP1 peptide were also determined. The N-terminal domain (Q384
      Q390 in the G alpha s protein) of the peptide adopted an alpha-helical
      conformation. However, the helical structure of the C-terminal domain (Q390-E392
      in the G alpha s protein) of the peptide was destabilized upon addition of the IP
      iLP1 peptide. These structural studies have implied that there are direct or
      indirect contacts between the IP iLP1 domain and the C-terminal residues of the G
      alpha s protein in the receptor/G protein coupling. The possible charge and
      hydrophobic interactions between the two peptides were also discussed. These data
      prompted intriguing speculations on the IP/G alpha s coupling which mediates
      vasodilatation and inhibition of platelet aggregation.

PMID- 16460021
TI  - Hybridization of complementary and homologous peptide nucleic acid oligomers to a
      guanine quadruplex-forming RNA.
AB  - Peptide nucleic acid (PNA) oligomers targeted to guanine quadruplex-forming RNAs
      can be designed in two different ways. First, complementary cytosine-rich PNAs
      can hybridize by the formation of Watson-Crick base pairs, resulting in hybrid
      PNA-RNA duplexes. Second, guanine-rich homologous PNAs can hybridize by the
      formation of G tetrads, resulting in hybrid PNA-RNA quadruplexes. UV thermal
      denaturation, circular dichroism, and fluorescence spectroscopy experiments were
      used to compare these two recognition modes and revealed 1:1 duplex formation for
      the complementary PNA and 2:1 (PNA2-RNA) quadruplex formation for the homologous
      PNA. Both hybrids were very stable, and hybridization was observed at low
      nanomolar concentrations. Hybrid quadruplex formation was equally efficient
      regardless of the PNA strand polarity, indicating a lack of interaction between
      the loop nucleobases on the PNA and RNA strands. The implications of this finding
      on sequence specificity as well as methods to improve affinity are also
      discussed.

PMID- 16460022
TI  - Delivery of phosphodiester oligonucleotides: can DOTAP/DOPE liposomes do the
      trick?
AB  - Delivering phosphodiester ONs (PO-ONs) remains an attractive but challenging goal
      in antisense therapy. Both in the literature and in our experiments, most
      cationic liposomes fail in generating an antisense effect with PO-ONs, while they
      succeed with chemically modified ONs such as phosphothioate ONs (PS-ONs). This
      work aims to explain the biological activity of PO- and PS-ONs delivered by
      DOTAP/DOPE liposomes based on a detailed understanding of their cell biological
      behavior by means of fluorescence correlation spectroscopy and confocal laser
      scanning microscopy. We conclude that DOTAP/DOPE liposomes are not suited to
      deliver PO-ONs due to the release of naked PO-ONs in the cytosol at the time of
      the endosomal escape of the liposomes and the subsequent rapid degradation of the
      naked PO-ONs. Carriers that would not release the PO-ONs upon endosomal escape
      but would continue to carry the PO-ONs until they arrive at the target mRNA could
      therefore be better suited to delivering PO-ONs. In the case of PS-ONs, the ONs
      are not degraded upon release at the time of the endosomal escape of the
      liposomes, creating a pool of intact, biologically active PS-ONs and thus making
      DOTAP/DOPE liposomes mainly suitable for delivering nuclease resistant ONs.
      However, the cells seemed to display an export pathway for removing intact PS-ONs
      from the cells, limiting the presence of naked PS-ONs in the nucleus to
      approximately 8 h following the delivery.

PMID- 16460023
TI  - Lytic activity and structural differences of amphipathic peptides derived from
      trialysin.
AB  - Trialysin is a pore-forming protein found in the saliva of Triatoma infestans
      (Hemiptera, Reduviidae), the insect vector of Chagas' disease. The protein is
      active against a broad range of cell types from bacteria to eukaryotic cells.
      Recognizing that the N-terminus of trialysin harbors the lytic motif [Amino, R.,
      Martins, R. M., Procopio, J., Hirata, I. Y., Juliano, M. A., and Schenkman, S.
      (2002) J. Biol. Chem. 277, 6207-6213], we designed a set of peptides scanning
      this region to investigate the structural basis of its biological function.
      Peptides encompassing residues 1-32 (P6), 1-27 (P7), and 6-32 (P5) efficiently
      induced lysis of the protozoan parasite Trypanosoma cruzi and Escherichia coli in
      the 0.4-9.0 microM range, while much higher concentrations were required to cause
      hemolysis. Other more internal peptides, including peptide P2 (residues 21-47)
      and others up to residue 52, were less effective. P6 turned out to be the most
      active of all. P7 has a significantly higher activity than P5 against E. coli,
      while P5 has a hemolytic activity comparable to that of P6. CD spectroscopy
      showed that all tested peptides acquire a comparable helical content in solvent
      mixtures or in detergent micelles. The solution structure of P2 and P5-P7 was
      determined in a 30% trifluoroethanol/water mixture by nuclear magnetic resonance.
      All peptides exhibit a structure characterized by a central helical fold, and
      except for P2, which does not show a continuous hydrophobic surface, they are
      amphipathic. The structural models show that P5 and P7 extend their structural
      similarities with the most active peptide, P6, in either the C-terminus or the N
      terminus. Amino acid substitutions in the N-terminus of P6 improved hemolysis but
      did not change the activity against T. cruzi. These results suggest that while
      amphipathicity is essential for the lytic activity, the selectivity of the active
      peptides for specific organisms appears to be associated with the structural
      features of their N- and C-termini.

PMID- 16460024
TI  - Possible role of a PXXP central hinge in the antibacterial activity and membrane
      interaction of PMAP-23, a member of cathelicidin family.
AB  - Cathelicidins are essential components of the innate immune system of mammals,
      providing them a weapon against microbial invasion. PMAP-23 adopting a helix
      hinge-helix structure with a central PXXP motif is a member of the cathelicidin
      family and has potent killing activities against a broad spectrum of microbial
      organisms. Although the antimicrobial effect of PMAP-23 is believed to be
      mediated by membrane disruption, many details of this event remain unclear. Here,
      we try to characterize the interaction between PMAP-23 and membrane
      phospholipids, focusing on the function of the central PXXP motif. PMAP-PA, in
      which the Pro residues were substituted by Ala, had significantly more alpha
      helical content than PMAP-23, but was less amphipathic and more damaging to human
      erythrocytes and zwitterionic liposomes. The observed differences in the
      structures and biological activities of PMAP-23 and PMAP-PA confirmed the
      functional importance of the central hinge PXXP motif, which enables PMAP-23 to
      adopt a well-defined amphipathic conformation along its entire length and to have
      selective antimicrobial activity. CD and Trp fluorescence studies using fragments
      corresponding to the two helical halves of PMAP-23 revealed that the N-terminal
      half binds to anionic phospholipids and is more stable than the C-terminal half.
      In addition, Trp fluorescence quench analyses revealed that the C-terminal helix
      inserts more deeply into the hydrophobic region of the membrane than the N
      terminal helix. Finally, observations made using biosensor technology enabled us
      to distinguish between the membrane binding and insertion steps, substantiating a
      proposed kinetic mode of the peptide-membrane interaction in which PMAP-23 first
      attaches to the membrane via the N-terminal amphipathic helix, after which
      bending and/or swiveling of the PXXP motif enables insertion of the C-terminal
      helix into the lipid bilayer.

PMID- 16460025
TI  - NMR determination of lysine pKa values in the Pol lambda lyase domain:
      mechanistic implications.
AB  - The base excision repair (BER) process requires removal of an abasic deoxyribose
      5-phosphate group, a catalytic activity that has been demonstrated for the N
      terminal 8 kDa domain of DNA polymerase beta (Pol beta), and for the homologous
      domain of DNA polymerase lambda (Pol lambda). Previous studies have demonstrated
      that this activity results from formation of a Schiff base adduct of the abasic
      deoxyribose C-1' with a lysine residue (K312 in the case of Pol lambda), followed
      by a beta-elimination reaction. To better understand the underlying chemistry, we
      have determined pKa values for the lysine residues in the Pol lambda lyase domain
      labeled with [epsilon-13C]lysine. At neutral pH, the H(epsilon) protons on 3 of
      the 10 lysine residues in this domain, K287, K291, and K312, exhibit chemical
      shift inequivalence that results from immobilization of the lysyl side chains.
      For K287 and K291, this results from the K287-E261 and K291-E298 salt bridge
      interactions, while for K312, immobilization apparently results from steric and
      hydrogen-bonding interactions that constrain the position of the lysine side
      chain. The pKa value of K312 is depressed to 9.58, a value indicating that at
      physiological pH K312 will exist predominantly in the protonated form. Titration
      of the domain with hairpin DNA containing a 5'-tetrahydrofuran terminus to model
      the abasic site produced shifts of the labeled lysine resonances that were in
      fast exchange but appeared to be complete at a stoichiometry of approximately
      1:1.3, consistent with a dissociation constant of approximately 1 microM. The
      epsilon-proton shifts of K273 were the most sensitive to the addition of the DNA,
      apparently due to changes in the relative orientation between K273 and W274 in
      the DNA complex. The average pKa values increased by 0.55, consistent with the
      formation of some DNA-lysine salt bridges and with the general pH increase
      expected to result from a reduction in the net positive charge of the complex. A
      general increase in the Hill coefficients observed in the complex is consistent
      with the screening of the interacting lysine residues by the DNA. The pKa of K312
      residue increased to 10.58 in the complex, probably due to salt bridge formation
      with the 5'-phosphate group of the DNA. The pKa values obtained for the lyase
      domain of Pol lambda in the present study are consistent with recent
      crystallographic studies of Pol beta complexed with 5-phosphorylated abasic sugar
      analogues in nicked DNA which reveal an open site with no obvious interactions
      that would significantly depress the pK value for the active site lysine residue.
      It is suggested that due to the heterogeneity of the damaged DNA substrates with
      which Pol lambda as well as other related polymerases may be required to bind,
      the unexpectedly poor optimization of the lyase catalytic site may reflect a
      compromise of flexibility with catalytic efficiency.

PMID- 16460026
TI  - Solution structure of discrepin, a new K+-channel blocking peptide from the alpha
      KTx15 subfamily.
AB  - Discrepin, isolated from the venom of the Venezuelan scorpion Tityus discrepans,
      blocks preferentially the I(A) currents of the voltage-dependent K+ channel of
      rat cerebellum granular cells in an irreversible way. It contains 38 amino acid
      residues with a pyroglutamic acid as the N-terminal residue [D'Suze, G., Batista,
      C. V., Frau, A., Murgia, A. R., Zamudio, F. Z., Sevcik, C., Possani, L. D., and
      Prestipino, G. (2004) Arch. Biochem. Biophys. 430, 256-63]. It is the most
      distinctive member of the alpha-KTx15 subfamily of scorpion toxins. Six members
      of the alpha-KTx15 subfamily have been reported so far to be specific for this
      subtype of the K+ channel; however, none of them have had their three-dimensional
      structure determined, and no information for the residues possibly involved in
      channel recognition and binding is available. Natural discrepin (n-discrepin) was
      prepared from scorpion venom, and its synthetic analogue (s-discrepin) was
      obtained by solid-phase synthesis. Analysis of two-dimensional 1H NMR spectra of
      n- and s-discrepin indicates that both peptides have the same structure. Here we
      report the solution structure of s-discrepin determined by NMR using 565
      meaningful distance constraints derived from the volume integration of the two
      dimensional NOESY spectrum, 22 dihedrals, and three hydrogen bonds. Discrepin
      displays the alpha/beta scaffold, characteristic of scorpion toxins. Some
      features of the proposed interacting surface between the toxin and channel as
      well as the opposite "alpha-helix surface" are discussed in comparison with those
      of other alpha-KTx15 members. Both n- and s-discrepin exhibit similar
      physiological actions as verified by patch-clamp and binding and displacement
      experiments.

PMID- 16460027
TI  - Structural and dynamic characterization of a vinculin binding site in the talin
      rod.
AB  - Talin is a key protein involved in linking integrins to the actin cytoskeleton.
      The long flexible talin rod domain contains a number of binding sites for
      vinculin, a cytoskeletal protein important in stabilizing integrin-mediated cell
      matrix junctions. Here we report the solution structure of a talin rod
      polypeptide (residues 1843-1973) which contains a single vinculin binding site
      (VBS; residues 1944-1969). Like other talin rod polypeptides, it consists of a
      helical bundle, in this case a four-helix bundle with a right-handed topology.
      The residues in the VBS important for vinculin binding were identified by
      studying the binding of a series of VBS-related peptides to the vinculin Vd1
      domain. The key binding determinants are buried in the interior of the helical
      bundle, suggesting that a substantial structural change in the talin polypeptide
      is required for vinculin binding. Direct evidence for this was obtained by NMR
      and EPR spectroscopy. [1H,15N]-HSQC spectra of the talin fragment indicate that
      vinculin binding caused approximately two-thirds of the protein to adopt a
      flexible random coil. For EPR spectroscopy, nitroxide spin labels were attached
      to the talin polypeptide via appropriately located cysteine residues.
      Measurements of inter-nitroxide distances in doubly spin-labeled protein showed
      clearly that the helical bundle is disrupted and the mobility of the helices,
      except for the VBS helix, is markedly increased. Binding of vinculin to talin is
      thus a clear example of the unusual phenomenon of protein unfolding being
      required for protein/protein interaction.

PMID- 16460028
TI  - Structure and activity of the N-terminal region of the eukaryotic cytolysin
      equinatoxin II.
AB  - The actinoporins are a family of proteins from sea anemones that lyse cells by
      forming pores in cell membranes. Sphingomyelin plays an important role in their
      lytic activity, with membranes lacking this lipid being resistant to these
      toxins. Pore formation by the actinoporin equinatoxin II (EqTII) proceeds by
      membrane binding via a surface rich in aromatic residues, followed by
      translocation of the N-terminal region to the membrane and, finally, across the
      bilayer to form a functional pore. A key feature of this mechanism is the ability
      of the N-terminal region to form a stable, bilayer-spanning helix in the
      membrane, which in turn requires dissociation of the N-terminus from the bulk of
      the protein and significant extension of the N-terminal helix of native EqTII. In
      this study the structures of three peptides corresponding to residues 11-29, 11
      32, and 1-32, respectively, of EqTII have been investigated by high-resolution
      nuclear magnetic resonance and Fourier transform infrared spectroscopy. The 32
      residue peptide lacks ordered secondary structure in water, but residues 6-28
      form a helix in dodecylphosphocholine micelles. Although this helix is long
      enough to span a bilayer membrane, this peptide and the shorter analogues display
      limited permeabilizing activity in large unilamellar vesicles and very weak
      hemolytic activity in human red blood cells. Thus, while the N-terminal region
      has the structural features required for this unusual mechanism of pore
      formation, the lack of activity of the isolated N-terminus shows that the bulk of
      the protein is essential for efficient pore formation by facilitating initial
      membrane binding, interacting with sphingomyelin, or stabilizing the oligomeric
      pore.

PMID- 16460029
TI  - Identification of coagulation factor VIII A2 domain residues forming the binding
      epitope for low-density lipoprotein receptor-related protein.
AB  - Regulation of the coagulation factor VIII (fVIII) level in circulation involves a
      hepatic receptor low-density lipoprotein receptor-related protein (LRP). One of
      two major LRP binding sites in fVIII is located within the A2 domain (A2), likely
      exposed within the fVIII complex with von Willebrand factor and contributing to
      regulation of fVIII via LRP. This work aimed to identify A2 residues forming its
      LRP-binding site, previously shown to involve residues 484-509. Isolated A2 was
      subjected to alanine-scanning mutagenesis followed by expression of a set of
      mutants in a baculovirus system. In competition and surface plasmon resonance
      assays, affinities of A2 mutants K466A, R471A, R484A, S488A, R489A, R490A, H497A,
      and K499A for LRP were found to be decreased by 2-4-fold. This correlated with
      1.3-1.5-fold decreases in the degree of LRP-mediated internalization of the
      mutants in cell culture. Combining these mutations into pairs led to cumulative
      effects, i.e., 7-13-fold decrease in affinity for LRP and 1.6-2.2-fold decrease
      in the degree of LRP-mediated internalization in cell culture. We conclude that
      the residues mentioned above play a key role in formation of the A2 binding
      epitope for LRP. Experiments in mice revealed an approximately 4.5 times shorter
      half-life for A2 in the circulation in comparison with that of fVIII. The half
      lives of A2 mutant R471A/R484A or A2 co-injected with receptor-associated
      protein, a classical ligand of LRP, were prolonged by approximately 1.9 and
      approximately 3.5 times, respectively, compared to that of A2. This further
      confirms the importance of the mutated residues for interaction of A2 with LRP
      and suggests the existence of an LRP-dependent mechanism for removing A2 as a
      product of dissociation of activated fVIII from the circulation.

PMID- 16460030
TI  - Phospholipids occupy the internal lumen of the c ring of the ATP synthase of
      Escherichia coli.
AB  - The occupancy of the central cavity of the membrane-embedded c ring of the ATP
      synthase of Escherichia coli was investigated with a photo-cross-linking
      approach. Single cysteine mutants were created at c subunit positions 4, 8, and
      11, which are oriented to the inside of the ring. These cysteines were alkylated
      with reagents carrying a photoactivatable substituent and illuminated. Subunit c
      and derivatives were then isolated and subjected to mass spectrometric analyses.
      The most noticeable product, which was found exclusively in irradiated samples,
      had a mass increase of 719 Da, consistent with a cross-link product between the
      substituted c subunit and phosphatidylethanolamine. Digestion with phospholipase
      C converted this product into one with a mass diminished by 126 Da, indicating
      that the phosphoethanolamine moiety was cleaved off. Hence, the cross-link forms
      to the diacylglycerol moiety of phosphatidylethanolamine. Control experiments
      showed that the subunit c-phospholipid adducts were formed in the ATP synthase
      complex in its natural membrane environment and were not artifacts arising from
      monomeric c subunits. We conclude therefore that the inner lumen of the c ring is
      occupied with phospholipids. No evidence was found for an extension of subunit a
      into this space.

PMID- 16460031
TI  - 3-Hydroxykynurenine oxidizes alpha-crystallin: potential role in
      cataractogenesis.
AB  - The alpha-, beta-, and gamma-crystallins are the major structural proteins of
      mammalian lenses. The human lens also contains tryptophan-derived UV filters,
      which are known to spontaneously deaminate at physiological pH and covalently
      attach to lens proteins. 3-Hydroxykynurenine (3OHKyn) is the third most abundant
      of the kynurenine UV filters in the lens, and previous studies have shown this
      compound to be unstable and to be oxidized under physiological conditions,
      producing H2O2. In this study, we show that methionine and tryptophan amino acid
      residues are oxidized when bovine alpha-crystallin is incubated with 3
      hydroxykynurenine. We observed almost complete oxidation of methionines 1 and 138
      in alphaA-crystallin and a similar extent of oxidation of methionines 1 and 68 in
      alphaB-crystallin after 48 h. Tryptophans 9 and 60 in alphaB-crystallin were
      oxidized to a lesser extent. AlphaA-crystallin was also found to have 3OHKyn
      bound to its single cysteine residue. Examination of normal aged human lenses
      revealed no evidence of oxidation of alpha-crystallin; however, oxidation was
      detected at methionine 1 in both alphaA- and alphaB-crystallin from human
      cataractous lenses. Age-related nuclear cataract is associated with coloration
      and insolubilization of lens proteins and extensive oxidation of cysteine and
      methionine residues. Our findings demonstrate that 3-hydroxykynurenine can
      readily catalyze the oxidation of methionine residues in both alphaB- and alphaA
      crystallin, and it has been reported that alpha-crystallin modified in this way
      is a poorer chaperone. Thus, 3-hydroxykynurenine promotes the oxidation and
      modification of crystallins and may contribute to oxidative stress in the human
      lens.

PMID- 16460032
TI  - Protective and inhibitory effects of various types of amphipols on the Ca2+
      ATPase from sarcoplasmic reticulum: a comparative study.
AB  - Amphipols are amphipathic polymers designed to replace or supplement detergents
      in membrane protein solution studies. Previous work has suggested both advantages
      and disadvantages to the use of a polyacrylate-based amphipol, A8-35, for
      studying the sarcoplasmic reticulum Ca2+-ATPase (SERCA1a). We investigated this
      issue further using a set of four amphipols with different chemical structures.
      Previous size exclusion chromatography experiments had shown that A8-35 and
      SERCA1a/A8-35 complexes aggregate under certain conditions. We show here that
      aggregation can be prevented by omitting calcium from buffers or by using a
      sulfonated version of A8-35. A8-35 had previously been shown to protect Ca2+
      ATPase from irreversible denaturation, while inhibiting its activity in a
      reversible manner. We show here that the other three amphipols tested also
      display these properties and that all four amphipols slow down backward calcium
      dissociation from the nonphosphorylated solubilized enzyme, a priori an unrelated
      step. As this calcium dissociation involves the opening up of the bundle of
      transmembrane ATPase segments, the slowing of this process may indicate that
      multipoint attachment of the polymers to the hydrophobic transmembrane surface
      damps protein dynamics ("Gulliver" effect). Damping might be the reason why
      amphipols also simultaneously protect membrane proteins against irreversible
      denaturation and may inhibit the activity of those of them that display large
      rearrangements of their transmembrane surface during their catalytic cycle.

PMID- 16460033
TI  - Factor XIIIa mediated attachment of S. aureus fibronectin-binding protein A
      (FnbA) to fibrin: identification of Gln103 as a major cross-linking site.
AB  - In the present study we investigated the role of factor XIIIa reactive Gln and
      Lys sites of staphylococcal FnbA receptor in cross-linking reaction with alpha
      chains of fibrin. For this purpose we produced two recombinant FnbA mutants in
      which either a single Gln103 site (1Q FnbA) or all identified reactive Gln103,
      105, 783, 830 and Lys157, 503, 620, 762 sites (4Q4K FnbA) were substituted with
      Ala residues. The results of FXIIIa-catalyzed incorporation of dansylcadaverine
      and dansylated peptide patterned on the NH2-terminal segment of fibronectin
      revealed that the reactivity of Gln substrate sites was drastically reduced in 1Q
      FnbA and 4Q4K FnbA mutants, while the reactivity of Lys substrate sites was only
      moderately decreased in 4Q4K FnbA. When it was tested in the FXIIIa-mediated
      fibrin cross-linking reaction, the 1Q FnbA mutant exhibited about 70-85%
      reduction in reactivity compared to that of the wild-type FnbA. These results
      demonstrate that FnbA participates in cross-linking to alpha chains of fibrin
      predominantly via its Gln103 reactive site. Several minor sites, including
      residues replaced in 4Q4K FnbA mutant, contributed to an additional 15-30% of the
      total fibrin cross-linking reactivity of FnbA. Comparison of amino acid sequences
      that follow the major reactive Gln site in FnbA and several known substrate
      proteins revealed that FXIIIa displays a preference for the glutamine residue in
      an xQAxBxPx sequence, where Q represents reactive glutamine, x is any amino acid
      residue, A is a polar residue, B is either valine or leucine, and P is proline.

PMID- 16460034
TI  - Identification and pharmacological characterization of domains involved in
      binding of CGRP receptor antagonists to the calcitonin-like receptor.
AB  - The calcitonin-like receptor (CLR) and the calcitonin receptor (CTR) interact
      with receptor activity-modifying protein 1 (RAMP1) at the cell surface to form
      heterodimeric receptor complexes. CLR and CTR are members of the class II (family
      B) G-protein-coupled receptors (GPCR) and bind calcitonin gene-related peptide
      (CGRP) with similar affinities when coexpressed with RAMP1. The observation that
      various nonpeptide CGRP receptor antagonists display a higher affinity for the
      CLR/RAMP1 complex than for CTR/RAMP1 provided an opportunity to investigate the
      molecular determinants of the differential receptor affinities of these
      antagonists. A chimeric receptor approach was utilized to identify key domains
      within CLR responsible for conferring high-affinity antagonist binding. Initial
      chimera experiments implicated distinct regions within CLR as responsible for the
      affinities of structurally diverse CGRP receptor antagonists. Dissection of these
      key regions implicated amino acids 37-63 located in the amino terminus of CLR as
      responsible for the high-affinity interaction of one structural class, while
      transmembrane domain (TM) 7 was responsible for the interaction of a second class
      of antagonist. A unique binding interaction in the amino terminus of CLR is
      consistent with the observation that these compounds also interact with the
      extracellular region of RAMP1 and could suggest the formation of a binding pocket
      between the two proteins. Conversely, a compound which interacted with TM7 did
      not display a similar RAMP1 dependence, suggesting an allosteric mechanism of
      antagonism. Collectively, these data provide insight into two alternative
      mechanisms of antagonism for this unique heterodimeric receptor complex.

PMID- 16460035
TI  - The kinase homology domain of receptor guanylyl cyclase C: ATP binding and
      identification of an adenine nucleotide sensitive site.
AB  - The role of the kinase homology domain (KHD) in receptor guanylyl cyclases is to
      regulate the activity of the catalytic guanylyl cyclase domain. The KHD lacks
      many of the amino acids required for phosphotransfer activity and, therefore, is
      not expected to possess kinase activity. Guanylyl cyclase activity of the
      receptor guanylyl cyclase C (GC-C) is modulated by ATP, and computational
      modeling showed that the KHD can adopt a structure similar to protein kinases,
      suggesting that the KHD is the site for ATP interaction. A monoclonal antibody,
      GCC:4D7, raised to the KHD of GC-C, fails to react with GC-C in the presence of
      ATP and ATP analogues that regulate GC-C catalytic activity, indicating that a
      conformational change occurs in the KHD on ATP binding. Mapping of the epitope of
      the antibody through the use of recombinant protein constructs and phage display
      showed that the epitope for GC-C:4D7 lies immediately C-terminal to a critical
      lysine residue (Lys516 in GC-C), required for ATP interaction in protein kinases.
      By employing a novel approach utilizing ATP-agarose affinity chromatography, we
      demonstrate that the intracellular domain of GC-C and the KHD bind ATP. Mutation
      of Lys516 to Ala abolishes ATP binding. Thus, this report is the first to show
      direct ATP binding to the pseudokinase domain of receptor guanylyl cyclase C, as
      well as to identify dramatic conformational changes that occur in this domain on
      ATP binding, akin to those seen in catalytically active protein kinases.

PMID- 16460036
TI  - Illuminated rhodopsin is required for strong activation of retinal guanylate
      cyclase by guanylate cyclase-activating proteins.
AB  - We have recently shown that activation of retinal guanylate cyclase (retGC) by GC
      activating proteins (GCAPs) is much stronger than that previously reported and
      that preincubation of photoreceptor outer segment homogenates with ATP or its
      analogue, adenylyl imidodiphosphate (AMP-PNP), is required for the strong
      activation [Yamazaki, A., Yu, H., Yamazaki, M., Honkawa, H., Matsuura, I.,
      Usukura, J., and Yamazaki, R. K. (2003) J. Biol. Chem. 278, 33150-33160]. Here we
      show that illuminated rhodopsin is essential for development of the AMP-PNP
      incubation effect. This was demonstrated by illumination of dark homogenates and
      treatments of illuminated homogenates with 11-cis-retinal and hydroxylamine prior
      to the AMP-PNP incubation and by measurement of the GCAP2 concentration required
      for 50% activation. We also found that the AMP-PNP incubation effect was not
      altered by addition of guanosine 5'-O-(3-thiotriphosphate), indicating that
      transducin activation is not required. It is concluded that illuminated rhodopsin
      is involved in retGC activation in two ways: to initiate the ATP incubation
      effect for preparation of retGC activation as shown here and to reduce the Ca2+
      concentrations through cGMP phosphodiesterase activation as already known. These
      two signal pathways may be activated in a parallel and perhaps proportional
      manner and finally converge for strong activation of retGC by Ca2+-free GCAPs.

PMID- 16460037
TI  - Hexacoordination of bacteriochlorophyll in photosynthetic antenna LH1.
AB  - The ability of chlorophylls to coordinate ligands is of fundamental structural
      importance for photosynthetic pigment-protein complexes, where in virtually all
      cases the pigment is thought to be in a pentacoordinated state. In this study,
      the correlation of the Q(X) transition energy with the coordination state of the
      central metal in bacteriochlorophyll is applied in investigating the pigment
      coordination state in bacterial photosynthetic antenna LH1. To facilitate a
      detailed spectral analysis in the Q(X) region, carotenoid-depleted forms of LH1
      are prepared and model LH1 are constructed with non-native carotenoids having
      blue-shifted absorption. The deconvolution of the Q(X) envelope in LH1 reveals
      that the band is the sum of two transitions, which peak near 590 and 607 nm,
      showing that a significant fraction (up to 25%) of hexacoordinated
      bacteriochlorophyll is present in the complex. The hexacoordination can be seen
      also in LH1 antennae from other species of purple photosynthetic bacteria. It
      seems correlated with the LH1 aggregation state and probably is a consequence of
      the structural flexibility of the assembled complex. The sixth ligand probably
      originates from the apoprotein and seems not to affect the chromophore core size.
      These findings show that in light-harvesting complexes a hexacoordinated state of
      bacteriochlorophyll is not uncommon. Its presence may be relevant to a correct
      assembly of the antenna and have functional consequences, as it results in a
      splitting of the pigment S2 excited state (Q(X)), i.e., the carotenoid excitation
      acceptor state, what might affect intracomplex carotenoid-to-bacteriochlorophyll
      energy transfer.

PMID- 16460038
TI  - Effects of substrate analogues and pH on manganese superoxide dismutases.
AB  - The effect of the substrate analogues azide and fluoride on the manganese(II)
      zero-field interactions of different manganese-containing superoxide dismutases
      (SOD) was measured using high-field electron paramagnetic resonance spectroscopy.
      Two cambialistic types, proteins that are active with manganese or iron, were
      studied along with two that were only active with iron and another that was only
      active with manganese. It was found that azide was able to coordinate directly to
      the pentacoordinated Mn(II) site of only the MnSOD from Escherichia coli and the
      cambialistic SOD from Rhodobacter capsulatus. The formation of a hexacoordinate
      azide-bound center was characterized by a large reduction in the Mn(II) zero
      field interaction. In contrast, all five SODs were affected by fluoride, but no
      evidence for hexacoordinate Mn(II) formation was detected. For both azide and
      fluoride, the extent of binding was no more than 50%, implying either that a
      second binding site was present or that binding was self-limiting. Only the
      Mn(II) zero-field interactions of the two SODs that had little or no activity
      with manganese were found to be significantly affected by pH, the manganese
      substituted iron superoxide dismutase from E. coli and the Gly155Thr mutant of
      the cambialistic SOD from Porphyromonas gingivalis. A model for anion binding and
      the observed pK involving tyrosine-34 is presented.

PMID- 16460039
TI  - pH dependence of proton translocation in the oxidative and reductive phases of
      the catalytic cycle of cytochrome c oxidase. The role of H2O produced at the
      oxygen-reduction site.
AB  - A study is presented on the pH dependence of proton translocation in the
      oxidative and reductive phases of the catalytic cycle of purified cytochrome c
      oxidase (COX) from beef heart reconstituted in phospholipid vesicles (COV).
      Protons were shown to be released from COV both in the oxidative and reductive
      phases. In the oxidation by O2 of the fully reduced oxidase, the H+/COX ratio for
      proton release from COV (R --> O transition) decreased from approximately 2.4 at
      pH 6.5 to approximately 1.8 at pH 8.5. In the direct reduction of the fully
      oxidized enzyme (O --> R transition), the H+/COX ratio for proton release from
      COV increased from approximately 0.3 at pH 6.5 to approximately 1.6 at pH 8.5.
      Anaerobic oxidation by ferricyanide of the fully reduced oxidase, reconstituted
      in COV or in the soluble case, resulted in H+ release which exhibited, in both
      cases, an H+/COX ratio of 1.7-1.9 in the pH range 6.5-8.5. This H+ release
      associated with ferricyanide oxidation of the oxidase, in the absence of oxygen,
      originates evidently from deprotonation of acidic groups in the enzyme
      cooperatively linked to the redox state of the metal centers (redox Bohr
      protons). The additional H+ release (O2 versus ferricyanide oxidation)
      approaching 1 H+/COX at pH < or = 6.5 is associated with the reduction of O2 by
      the reduced metal centers. At pH > or = 8.5, this additional proton release takes
      place in the reductive phase of the catalytic cycle of the oxidase. The H+/COX
      ratio for proton release from COV in the overall catalytic cycle, oxidation by O2
      of the fully reduced oxidase directly followed by re-reduction (R --> O --> R
      transition), exhibited a bell-shaped pH dependence approaching 4 at pH 7.2. A
      mechanism for the involvement in the proton pump of the oxidase of H+/e-
      cooperative coupling at the metal centers (redox Bohr effects) and protonmotive
      steps of reduction of O2 to H2O is presented.

PMID- 16460040
TI  - Photooxidation pathway of chlorophyll Z in photosystem II as Studied by Fourier
      transform infrared spectroscopy.
AB  - The oxidation pathway of chlorophyll Z (ChlZ) in photosystem II (PSII) at
      cryogenic temperatures was studied by means of light-induced Fourier transform
      infrared (FTIR) difference spectroscopy. To examine the involvement of redox
      active beta-carotene (Car) in the pathway, two Car molecules in Mn-depleted PSII
      membranes of spinach were selectively bleached by illumination at 250 K in the
      presence of ferricyanide and silicomolybdate. Successful bleaching of Car was
      demonstrated by disappearance of the light-induced FTIR signals of Car+ at 1465,
      1440, and 1147 cm(-1) at 80 K under an oxidative condition. Even in the Car
      bleached PSII, the ChlZ+/ChlZ signal at 1713/1687 cm(-1), which is attributed to
      the upshift of the 9-keto C=O band of ChlZ upon its oxidation, was induced by
      illumination at 80 K retaining about 80% of the intensity of the control PSII
      sample. The concomitant appearance of shoulders at 1727/1699 cm(-1) may indicate
      that both of the two ChlZ molecules on the D1 and D2 sides are photooxidized. The
      multiphasic kinetics of formation of the ChlZ+/ChlZ signal by continuous
      illumination at 80 K were mostly unchanged by Car depletion, while the formation
      rates at 210 K were appreciably reduced in Car-bleached PSII. These results
      indicate that there are electron-transfer pathways from ChlZ to P680+ that do not
      involve Car, and they are indeed dominant at 80 K. Although the pathways via Car
      are mostly blocked at this temperature, the contribution of such pathways to ChlZ
      oxidation becomes significant at higher temperatures.

PMID- 16460041
TI  - Autophosphorylation of Arabidopsis nucleoside diphosphate kinase 2 occurs only on
      its active histidine residue.
AB  - Arabidopsis nucleoside diphosphate kinase 2 (NDPK2) is a component in the
      phytochrome-mediated light signaling. In the present study, its
      autophosphorylation was investigated. Acid-stable and alkali-stable
      phosphorylated residues were analyzed under two different conditions. Results
      revealed that NDPK2 is phosphorylated only on its active histidine residue His197
      and the presence of serine/threonine phosphorylation is an experimental artifact
      due to the harsh condition applied in the treatment of the phosphorylated protein
      sample. To resolve the controversy of whether serine/threonine phosphorylation of
      NDPK occurs as has been suggested by other NDPK studies, NDPK2 putative
      phosphorylation site mutants were generated and examined. No serine/threonine
      phosphorylation was identified in NDPK2 or implicated in its enzymatic activity.
      Further studies indicated that the low enzymatic activity and autophosphorylation
      level of NDPK2 mutant S199A are shown to be due to a damaged H-bonding with the
      active histidine residue His197 in the nucleotide-binding pocket. In addition,
      NDPK2 Kpn loop mutant T182A was found to possess an extremely low enzymatic
      activity and almost no autophosphorylation, suggesting the importance of the
      oligomeric states of NDPK2 in NDPK2 functioning.

PMID- 16460042
TI  - Identification of 3-hydroxykynurenine bound to proteins in the human lens. A
      possible role in age-related nuclear cataract.
AB  - Age-related nuclear (ARN) cataract is a major cause of world blindness. With the
      onset of ARN cataract, the normally transparent and colorless lens becomes opaque
      and can take on colors ranging from orange, brown, and even black. The molecular
      basis for this remarkable transformation is unknown. ARN cataract is also
      characterized by extensive oxidation, insolubilization, and cross-linking of
      polypeptides, particularly in the nucleus of the lens. It has been postulated
      that 3-hydroxykynurenine (3OHKyn) may be involved in these changes. This
      endogenous tryptophan metabolite is readily oxidized and is involved in the
      tanning of moth cocoons and the formation of pigments in the eyes of butterflies.
      3OHKyn is a component of our primate-specific UV-filter pathway, and the brownish
      hue of ARN cataract lenses is also unique to humans. Because numerous colored
      compounds can be produced by autoxidation of 3OHKyn, this process could provide
      an explanation for the variety of lens colors and other changes seen in ARN
      cataract. For such a theory to be tenable, it needs to be demonstrated that
      3OHKyn is bound to proteins in the human lens. Here, we show that all normal
      lenses older than 50 have 3OHKyn covalently attached to the nuclear proteins,
      most likely via cysteine residues. If indeed 3OHKyn is implicated in ARN
      cataract, a reduction in the levels that are bound in cataract, compared to
      normal lenses, would be expected. In agreement with this hypothesis, no bound
      3OHKyn could be detected in proteins isolated from ARN cataract lenses.

PMID- 16460044
TI  - Targeted cross-linking of the human beta-globin gene in living cells mediated by
      a triple helix forming oligonucleotide.
AB  - Triple helix forming oligonucleotides (TFOs) may have utility as gene targeting
      reagents for "in situ" gene therapy of genetic disorders. Triplex formation is
      challenged by negative charge repulsion between third strand and duplex
      phosphates, and destabilizing positive charge repulsion between adjacent
      protonated cytosines within pyrimidine motif third strands. Here we describe the
      synthesis of TFOs designed to target a site in the human beta-globin gene, which
      is the locus for mutations that underlie the beta-globinopathies, including
      sickle cell anemia. The target is an uninterrupted polypurine:polypyrimidine
      sequence, containing four adjacent cytosines, next to a psoralen cross-link site.
      Pyrimidine motif TFOs that contained four adjacent cytosines or 5-methylcytosines
      did not form stable triplexes at physiological pH, despite the introduction of
      otherwise stabilizing base and sugar analogues. We synthesized a series of pso
      TFOs containing 2'-O-methyl (OMe) and 2'-O-aminoethoxy substitutions (AE), as
      well as 8-oxo-adenine (A8) and 2'-O-methylpseudoisocytidine (P) as neutral
      cytosine replacements. Thermal stability measurements indicated that TFOs with A8
      did not meet criteria established in previous work. However, TFOs with P did form
      triplexes with appropriate T(m) and k(ON) values. A pso-TFO with AE and P
      residues was sufficiently active to permit the determination of targeting in
      living cells by direct measurement of cross-link formation at the target site.
      Our results validate the modification format described in our previous studies
      and indicate that P substitutions are an effective solution to the problem of
      targeting genomic sequences containing adjacent cytosines.

PMID- 16460043
TI  - Pre-steady-state binding of damaged DNA by XPC-hHR23B reveals a kinetic mechanism
      for damage discrimination.
AB  - The XPC-hHR23B complex (XPC-hHR23B) is a heterodimeric protein required for the
      initial step of DNA damage recognition in the global nucleotide excision repair
      (NER) pathway. A strong preference of XPC-hHR23B for UV- and cisplatin-damaged
      DNA has previously been demonstrated using equilibrium binding assays. To better
      understand the molecular mechanism of damage recognition by XPC-hHR23B, we
      carried out the pre-steady-state kinetic analysis of the XPC-hHR23B-DNA
      interactions using a stopped-flow fluorescence assay. XPC-hHR23B displays a
      faster k(on) for cisplatin- and UV-damaged duplex DNA than for undamaged DNA,
      with additional, minor effects on the k(off) rates. XPC-hHR23B has a high
      affinity for undamaged single-stranded DNA compared to duplex DNA, which can be
      largely attributed to a high rate of association. However, cisplatin damage on
      single-stranded DNA reduced the overall level of binding by a factor of 7, with
      nearly equal contributions from changes to the k(on) and k(off) rates. Together,
      these results support a model for initial damage recognition by XPC-hHR23B that
      is dependent on structural changes in the DNA, and not adduct chemistry.

PMID- 16460045
TI  - Mechanistic studies of choline oxidase with betaine aldehyde and its isosteric
      analogue 3,3-dimethylbutyraldehyde.
AB  - Choline oxidase catalyzes the four-electron oxidation of choline to glycine
      betaine via two sequential FAD-dependent reactions in which betaine aldehyde is
      formed as an intermediate. The chemical mechanism for the oxidation of choline
      catalyzed by choline oxidase was recently elucidated by using kinetic isotope
      effects [Fan, F., and Gadda, G. (2005) J. Am. Chem. Soc. 127, 2067-2074]. In this
      study, the oxidation of betaine aldehyde has been investigated by using
      spectroscopic and kinetic analyses with betaine aldehyde and its isosteric
      analogue 3,3-dimethylbutyraldehyde. The pH dependence of the kcat/Km and kcat
      values with betaine aldehyde showed that a catalytic base with a pKa of
      approximately 6.7 is required for betaine aldehyde oxidation. Complete reduction
      of the enzyme-bound flavin was observed in a stopped-flow spectrophotometer upon
      anaerobic mixing with betaine aldehyde or choline at pH 8, with similar k(red)
      values > or = 48 s(-1). In contrast, only 10-26% of the enzyme-bound flavin was
      reduced by 3,3-dimethylbutyraldehyde between pH 6 and 10. Furthermore, this
      compound acted as a competitive inhibitor versus choline. NMR spectroscopic
      analyses indicated that betaine aldehyde exists predominantly (99%) as a diol
      form in aqueous solution. In contrast, the thermodynamic equilibrium for 3,3
      dimethylbutyraldehyde favors the aldehyde (> or = 65%) over the hydrated form in
      the pH range from 6 to 10. The keto species of 3,3-dimethylbutyraldehyde is
      reactive toward enzymic nucleophiles, as suggested by the kinetic data with NAD+
      dependent yeast aldehyde dehydrogenase. The data presented suggest that choline
      oxidase utilizes the hydrated species of the aldehyde as substrate in a mechanism
      for aldehyde oxidation in which hydride transfer is triggered by an active site
      base.

PMID- 16460046
TI  - Effect of the casting solvent on the morphology of poly(styrene-b-isoprene)
      diblock copolymer/magnetic nanoparticle mixtures.
AB  - We investigate the effect of the casting solvent on the phase behavior of a
      cylinder-forming poly(styrene-b-isoprene) (PS-b-PI) diblock copolymer mixed with
      marginally selective gamma-Fe2O3 nanoparticles. Notably, for the mixtures of PS-b
      PI/gamma-Fe2O3 nanoparticles cast with toluene, which is a neutral solvent for
      both PS and PI blocks, the latticelike aggregates of gamma-Fe2O3 nanoparticles,
      originating from magnetic dipole interactions, induce an intriguing transition
      from hexagonal cylinders to body-centered cubic spheres via undulated cylinders
      whereas the neat block copolymer does not show such an order-order transition. In
      contrast, when PI-selective hexane is used, the nanoparticles are selectively
      incorporated into the PI domains, and the microphase-separated hexagonal cylinder
      morphology gradually loses its long-range order upon increasing the nanoparticle
      concentration. The structural information obtained from small-angle X-ray
      scattering is also in good agreement with transmission electron microscopy images
      and differential scanning calorimetry results.

PMID- 16460047
TI  - Patterned colloid assembly by grafted photochromic polymer layers.
AB  - Quartz surfaces and colloidal silica particles were derivatized with a
      poly(methyl methacrylate) copolymer containing spirobenzopyran (SP) photochromic
      molecules in the pendant groups at a concentration of 20 mol %. Two-photon near
      IR excitation (approximately 780 nm) was then used to create chemically distinct
      patterns on the modified surfaces through a photochromic process of SP
      transformation to the zwitterionic merocyanine (MC) isomer. The derivatized
      colloids were approximately 10 times more likely to adsorb onto the
      photoswitched, MC regions. Surface coverage and adsorption kinetics have been
      compared to the mean-field model of irreversible monolayer adsorption.

PMID- 16460048
TI  - Microsphere organization of nanorods directed by PEG linear polymer.
AB  - We demonstrate the sphere organization of ZnO, Bi2S3, MnO2, and La(OH)3 nanorods
      directed by PEG linear polymer. Our study shows that zinc, bismuth, manganese, or
      lanthanum species added to PEG solutions, in which PEG molecules are well
      dissolved in a coil state, convert the polymer coils to aggregate structures,
      which further aggregate into micrometer-sized M(n+)-PEG globules. The
      concentration of metallic species is higher in the globules than in bulk
      solutions. The surfaces of the globules act as soft templates for the initial
      nucleation and thereafter the growth of the nanorods. Finally, echinus-type
      assemblies of single-crystalline nanorods form by the metallic species
      hydrolyzing or reacting with deposition agents. This approach opens the
      possibility of using polymers as soft templates to control the organization of
      nano building units into designed structures.

PMID- 16460049
TI  - Nanolithographic write, read, and erase via reversible nanotemplated
      nanostructure electrodeposition on alkanethiol-modified Au(111) in an aqueous
      solution.
AB  - A write, read, and erase nanolithographic method, combining in situ
      electrodeposition of metal nanostructures with atomic force microscopy (AFM)
      nanoshaving of a 1-hexadecanethiol (HDT) self-assembled monolayer (SAM) on
      Au(111) in an aqueous solution, is reported. The AFM tip defines the local
      positioning of nanotemplates via the irreversible removal of HDT molecules.
      Nanotemplates with lateral dimensions as narrow as 25 nm are created. The
      electroactive nanotemplates determine the size, shape, and position of the metal
      nanostructures. The potential applied to the substrate controls the amount of
      metal deposited and the kinetics of the deposition. Metal nanostructures can be
      reversibly and repeatedly electrodeposited and stripped out of the nanotemplates
      by applying appropriate potentials.

PMID- 16460050
TI  - Protein-assisted solubilization of single-walled carbon nanotubes.
AB  - We report a simple method that uses proteins to solubilize single-walled carbon
      nanotubes (SWNTs) in water. Characterization by a variety of complementary
      techniques including UV-Vis spectroscopy, Raman spectroscopy, and atomic force
      microscopy confirmed the dispersion at the individual nanotube level. A variety
      of proteins differing in size and structure were used to generate individual
      nanotube solutions by this noncovalent functionalization procedure. Protein
      mediated solubilization of nanotubes in water may be important for biomedical
      applications. This method of solubilization may also find use in approaches for
      controlling the assembly of nanostructures, and the wide variety of functional
      groups present on the adsorbed proteins may be used as orthogonal reactive
      handles for the functionalization of carbon nanotubes.

PMID- 16460052
TI  - Underwater superhydrophobicity: theoretical feasibility.
AB  - The possibility of underwater superhydrophobicity is theoretically analyzed.
      Thermodynamic equilibrium and stability conditions are formulated, and the design
      goal is defined as minimizing the solid-liquid contact area. It is shown that for
      sufficiently high roughness ratios, underwater superhydrophobicity may be
      feasible and thermodynamically stable. In addition, some generic design
      optimization considerations are demonstrated.

PMID- 16460051
TI  - One-step advanced preparation of surface-functional peptide nanospheres by the
      polymerization of L-phenylalanine N-carboxyanhydride with dual initiators.
AB  - Surface-grafted peptide nanospheres consisting of hydrophobic poly(L
      phenylalanine) with hydrophilic poly(ethylene glycol) (PEG) grafts were
      successfully prepared by the one-step polymerization of L-phenylalanine N
      carboxyanhydride with the dual initiators of hydrophobic n-butylamine and
      hydrophilic NH2-monoterminated PEG (NH2-PEG). The monodispersed peptide
      nanospheres were stably self-assembled during polymerization in a mixture of
      water/dimethyl sulfoxide to create a colloidal solution, but only aggregated in
      water or organic solvents. When n-butylamine or NH2-PEG was used as a solitary
      initiator, the peptide nanospheres were not formed. The peptide nanospheres
      showed high dispersion-stability in water, and their diameter was approximately
      300 nm. Furthermore, the peptide nanospheres were well-redispersed in water,
      retaining the same diameter and monodispersity even after lyophilization. Peptide
      nanospheres with the functional carboxylic acid on their graft layer were also
      successfully prepared by the one-step preparation method. This one-step
      preparation method of surface-grafted peptide nanospheres will be useful as an
      advanced technology to develop biodegradable functional nanospheres.

PMID- 16460053
TI  - Isoelectric point of fluorite by direct force measurements using atomic force
      microscopy.
AB  - Interaction forces between a fluorite (CaF2) surface and colloidal silica were
      measured by atomic force microscopy (AFM) in 1 x 10(-3) M NaNO3 at different pH
      values. Forces between the silica colloid and fluorite flat were measured at a
      range of pH values above the isoelectric point (IEP) of silica so that the forces
      were mainly controlled by the fluorite surface charge. In this way, the IEP of
      the fluorite surface was deduced from AFM force curves at pH approximately 9.2.
      Experimental force versus separation distance curves were in good agreement with
      theoretical predictions based on long-range electrostatic interactions, allowing
      the potential of the fluorite surface to be estimated from the experimental force
      curves. AFM-deduced surface potentials were generally lower than the published
      zeta potentials obtained from electrokinetic methods for powdered samples.
      Differences in methodology, orientation of the fluorite, surface carbonation, and
      equilibration time all could have contributed to this difference.

PMID- 16460054
TI  - Light-harvesting energy transfer and subsequent electron transfer of cationic
      porphyrin complexes on clay surfaces.
AB  - A novel energy-transfer system involving nonaggregated cationic porphyrins
      adsorbed on an anionic-type clay surface and the electron-transfer reaction that
      occurs after light harvesting are described. In the clay-porphyrin complexes,
      photochemical energy transfer from excited singlet zinc porphyrins to free-base
      porphyrins proceeds. The photochemical electron-transfer reaction from an
      electron donor in solution (hydroquinone) to the adsorbed porphyrin in the
      excited singlet state was also examined. Because the electron-transfer rate from
      the hydroquinone to the excited singlet free-base porphyrin is larger than that
      to the excited singlet zinc porphyrin, we conclude that the energy transfer
      accelerates the overall electron-transfer reaction.

PMID- 16460055
TI  - Controlling chemical reactivity at solid-solution interfaces by means of
      hydrophobic magnetic nanoparticles.
AB  - Hydrophobic magnetic nanoparticles are employed to reversibly regulate the
      hydrophobic/hydrophilic properties of surfaces and to control the
      electrochemistry and bioelectochemistry at chemically modified electrodes.
      Selective bioelectrocatalytic transformations at relay-functionalized electrodes
      are accomplished by the magnetic attractions of the hydrophobic magnetic
      nanoparticles with coadsorbed hydrophobic redox relays to the electrode. The
      selective activation of one of two biocatalysts solubilized in the aqueous
      electrolyte solution in the absence or presence of hydrophobic magnetic
      nanoparticles results in the specific activation of bioelectrocatalytic
      processes. The magnetic attraction and retraction of hydrophobic magnetic
      nanoparticles to and from semiconductor nanoparticle (CdS)-functionalized
      electrodes enable the control of the photocurrent directions at the electrode
      from cathodic to anodic directions, respectively. The magnetic attraction of the
      hydrophobic magnetic nanoparticles to the surfaces is also employed to control
      biorecognition and biocatalytic transformations at solid supports. The magnetic
      attraction and retraction of the hydrophobic magnetic nanoparticles to and from
      the surfaces allow the blockage and activation of DNA hybridization,
      polymerization, and enzymatic digestion, respectively.

PMID- 16460056
TI  - Photophysical effects between spirobenzopyran-methyl methacrylate-functionalized
      colloidal particles.
AB  - Colloidal particles were derivatized with end-grafted polymethylmethacrylate
      polymer brushes containing varying concentrations of spirobenzopyran photochromic
      molecules. The polymers were grown from initiator-functionalized silica particles
      by an atom-transfer radical polymerization (ATRP). These core-shell colloids
      formed stable suspensions in toluene with the spirobenzopyran in its closed,
      nonpolar form. However, UV-induced photoswitching of the photochrome to its open,
      polar merocyanine isomer caused rapid aggregation. The nature of this colloidal
      stability transition was examined with respect to the spirobenzopyran content in
      the polymeric brush and solvent polarity. Turbidimetry, wettability studies, UV
      vis spectroscopy, suspension rheology, SEM, and visual inspection were utilized
      to characterize the system photoswitchability. It was found that the system
      exhibiting the greatest transition in toluene was the copolymer brush composed of
      20% spirobenzopyran and 80% methyl methacrylate.

PMID- 16460057
TI  - Organized collapse structures in mixtures of chiral ethyl 2-azido-4-fluoro-3
      hydroxystearates.
AB  - Monolayers of enantiomeric compounds as well as diastereomeric mixtures and
      racemic/diastereomeric mixtures of ethyl 2-azido-4-fluoro-3-hydroxystearates have
      been investigated using surface pressure-area isotherms and Brewster angle
      microscopy. All monolayers collapse out of the liquid-expanded phase, forming 3D
      collapse structures which were visualized with scanning force microscopy. The
      enantiomeric compound and the diastereomeric mixtures form unique fiber-like
      network structures with heights between 20 and 40 nm. Interestingly, the shape of
      the enantiomeric fiber structures is straight, whereas the diastereomeric
      mixtures exhibit curved fibers of different sizes. The racemic mixture however
      forms circular 10 nm high and 20-50 microm broad structures. The shape of
      unconventional collapse structures could be changed by using distinct ratios of
      diastereomeric or racemic/diastereomeric mixed compounds.

PMID- 16460058
TI  - Self-assembly of a nonionic photoresponsive surfactant under varying irradiation
      conditions: a small-angle neutron scattering and cryo-TEM study.
AB  - We have used small-angle neutron scattering (SANS), and cryogenic transmission
      electron microscopy (cryo-TEM) to determine the structure of aggregates formed by
      the photoresponsive surfactants diethylene glycol mono(4',4-butyloxy, butyl
      azobenzene) (C4AzoOC4E2) and diethylene glycol mono(4',4-hexyloxy, butyl
      azobenzene) (C4AzoOC6E2) under different illumination conditions. At high
      concentrations, the self-assembly behavior of these surfactants changes
      remarkably in response to different radiation conditions. The trans isomers
      assemble into bilamellar (C4AzoOC4E2) and unilamellar (C4AzoOC6E2) vesicles,
      while the cis isomers (under UV light) form bicontinuous phases. These light
      induced structural changes are attributed to a change in the sign of the Gaussian
      rigidity, which is the direct result of azobenzene photoisomerization.

PMID- 16460059
TI  - Influence of halogen substituents on the self-assembly of oligothiophenes--a
      combined STM and theoretical approach.
AB  - Iodinated quaterthiophenes 2-3 have been synthesized and their self-assembling
      behavior investigated at the liquid-solid interface by means of high-resolution
      scanning tunneling microscopy in comparison to parent oligothiophene 1. All three
      compounds spontaneously give well-ordered 2D crystalline monolayers at the
      graphite surface and order in a lamella-type arrangement of the conjugated
      backbones concomitant with an interlocking of the alkyl side chains.
      Symmetrically substituted oligothiophenes 1 and 3 without a relevant dipole
      moment self-assemble in a similar fashion, exhibiting comparable unit cells,
      whereas monoiodo derivative 2 arranges as pairs along the lamella axis due to the
      presence of a permanent dipole moment induced by the polarizable halogen group.
      Corroborated by quantum chemical calculations, novel head-to-head (iodo-iodo)
      intermolecular interactions were found to take place for this unsymmetrical
      derivative. The investigation of mixed solutions clearly reveals that at the
      solid-liquid interface a homogeneous layer of this compound is formed, which
      comprises the highest packing density leading to a separation process at the
      interface.

PMID- 16460060
TI  - Phase behavior of diglycerol fatty acid esters-nonpolar oil systems.
AB  - Phase behavior of diglycerol fatty acid esters (Qn-D, where n represents the
      carbon number in the alkyl chain length of amphiphile, n = 10-16) were
      investigated in different nonpolar oils, liquid paraffin (LP70), squalane, and
      squalene. There is surfactant solid at lower temperature, and the surfactant
      solid does not swell in oil, and the melting temperature is almost constant in a
      wide range of compositions. In all of the systems, a lamellar liquid crystal
      (L(alpha)) is formed in a concentrated region at a temperature between the solid
      melting temperature and the isotropic two- or single-phase regions. In the dilute
      regions, reverse vesicles are formed in L(alpha) + O regions. There are two
      liquid-phase regions above the L(alpha) present region. This two-phase boundary
      corresponds to the cloud-point curve of nonionic surfactant aqueous solutions.
      However, instead of being less soluble in water at high temperature for the cloud
      point, the surfactant becomes more soluble in the organic solvents at high
      temperature. Namely, the effect of temperature on the solubility is opposite to
      the clouding phenomenon. When the hydrocarbon chain of the diglycerol surfactant
      decreases, the two-phase region becomes wider. In the case of a fixed surfactant,
      the surfactant is most miscible with squalene (narrowest two-phase regions) and
      the order of dissolutions tendency is squalene > LP70 > squalane. These results
      show that the hydrophilic moiety (diglycerol group) is more insoluble in oil
      compared with that of a conventional poly(oxyethylene)-type nonionic surfactant.
      Formation of reversed rodlike micelles was confirmed by SAXS scattering curve.
      When the hydrocarbon chain of surfactant is short, the micellar size becomes
      larger. In a fixed surfactant system, the reverse micellar size increases by
      changing oil from squalene to LP70. A small amount of water induces a dramatic
      elongation of reverse micelles.

PMID- 16460061
TI  - Synthesis and characterization of large colloidal cobalt particles.
AB  - Large colloidal environmentally stable silica-coated cobalt particles were
      synthesized by combining the sodium borohydride reduction in aqueous solution and
      the Stober method. Low size polydisperse cobalt spheres with an average size of
      95 nm were synthesized by using a borohydride reduction method and were
      subsequently coated with a thin layer of silica by means of hydrolysis and
      condensation of tetraethylorothosilicate (TEOS) in an aqueous/ethanolic solution.
      The large uniform cobalt spheres consist of smaller metallic Co clusters,
      explaining the superparamagnetic behavior of the spheres. The particles were
      investigated by transmission electron microscopy (TEM) and vibrating sample
      magnetometry (VSM).

PMID- 16460062
TI  - Evaporation-induced particle microseparations inside droplets floating on a chip.
AB  - We describe phenomena of colloidal particle transport and separation inside
      single microdroplets of water floating on the surface of dense fluorinated oil.
      The experiments were performed on microfluidic chips, where single droplets were
      manipulated with alternating electric fields applied to arrays of electrodes
      below the oil. The particles suspended in the droplets were collected in their
      top region during the evaporation process. Experimental results and numerical
      simulations show that this microsepration occurs as a result of a series of
      processes driven by mass and heat transfer. An interfacial tension gradient
      develops on the surface of the droplet as a result of the nonuniform temperature
      distribution during the evaporation. This gradient generates an internal
      convective Marangoni flow. The colloidal particles transported by the flow are
      collected in the top of the droplets by the hydrodynamic flux, compensating for
      evaporation through the exposed top surface. The internal flow pattern and
      temperature distribution within evaporating droplets were simulated using finite
      element calculations. The results of the simulation were consistent with
      experiments using tracer particles. Such microseparation processes can be used
      for on-chip synthesis of advanced particles and innovative microbioassays.

PMID- 16460063
TI  - Supramolecular self-assembly of multiblock copolymers in aqueous solution.
AB  - A unique pH-dependent phase behavior from a copolymer micellar solution to a
      collapsed hydrogel with micelles ordered in a hexagonal phase was observed. Small
      angle neutron scattering (SANS) was used to follow the pH-dependent structural
      evolution of micelles formed in a solution of a pentablock copolymer consisting
      of poly((diethylaminoethyl methacrylate)-b-(ethylene oxide)-b-(propylene oxide)-b
      (ethylene oxide)-b-(diethylaminoethyl methacrylate)) (PDEAEM25-b-PEO100-b-PPO65-b
      PEO100-b-PDEAEM25). Between pH 3.0 and pH 7.4, we observed the presence of
      charged spherical micelles. Increasing the pH of the micelle solution above pH
      7.4 resulted in increasing the size of the micelles due to the increasing
      hydrophobicity of the PDEAEM blocks above their pKa of 7.6. The increase in size
      of the spherical micelles resulted in a transition to a cylindrical micelle
      morphology in the pH range 8.1-10.5, and at pH >11, the copolymer solution
      undergoes macroscopic phase separation. Indeed, the phase separated copolymer
      sediments and coalesces into a hydrogel structure that consists of 25-35 wt %
      water. Small-angle X-ray scattering (SAXS) clearly indicated that the hydrogel
      has a hexagonal ordered phase. Interestingly, the process is reversible, as
      lowering of the pH below 7.0 leads to rapid dissolution of the solid into
      homogeneous solution. We believe that the hexagonal structure in the hydrogel is
      a result of the organization of the cylindrical micelles due to the increased
      hydrophobic interactions between the micelles at 70 degrees C and pH 11. Thus we
      have developed a pH-/temperature-dependent, reversible hierarchically self
      assembling block copolymer system with structures spanning nano- to microscale
      dimensions.

PMID- 16460064
TI  - Thermoresponsiveness of hybrid micelles from poly(ethylene glycol)-block-poly(4
      vinylpyridium) cations and SO4(2-) anions in aqueous solutions.
AB  - The SO4(2-)-induced micellization of poly(ethylene glycol)-block-poly(4
      vinylpyridium) (PEG110-b-P(4-VPH+)35) and the thermoresponsiveness of these
      hybrid micelles are studied by dynamic and static light scattering. When the
      concentration of H2SO4 is high enough, PEG110-b-P(4-VPH+)35 forms stable hybrid
      micelles with an ionic core of P(4-VPH+)35/SO4(2-) and a PEG corona at 25 degrees
      C. The formation of the hybrid micelles is reversible. A thermodynamic
      equilibrium exists between the hybrid micelles and PEG110-b-P(4-VPH+)35 unimers.
      The shifts of the equilibrium are mainly attributed to the variation of the
      electrostatic energy and entropic energy of the system. Therefore, the
      temperature can determine the states of the equilibrium, which means that the
      dissociation or the formation of the hybrid micelles can be triggered by just
      varying the temperature.

PMID- 16460065
TI  - Self-assembly of beta-cyclodextrin in water. Part 1: Cryo-TEM and dynamic and
      static light scattering.
AB  - In this article, we report evidence of beta-cyclodextrin (beta-CD) self
      aggregation in water. A critical aggregation concentration (cac) between 2 and 3
      mM was determined by using dynamic (DLS) and static (SLS) light scattering to
      investigate the presence of beta-cyclodextrin aggregates. Transmission electron
      microscopy at cryogenic temperature (Cryo-TEM) was used to detect the structural
      features of cyclodextrin self-aggregates. The results show the occurrence of
      polymorphism depending on the beta-CD concentration: polydisperse nearly
      spherical objects with diameters of about 100 nm are present at lower
      concentrations, whereas micrometer planar aggregates are predominant at higher
      concentrations.

PMID- 16460066
TI  - Colloidal interactions between asphaltene surfaces in aqueous solutions.
AB  - Asphaltene at oil/water interfaces plays a dominant role in the recovery of crude
      oil. In this study, asphaltene monolayer films were deposited on hydrophobic
      silicon wafers and silica spheres from oil-water interfaces using a Langmuir
      interfacial trough. The morphology of the deposited asphaltene films was
      characterized with an atomic force microscope (AFM). The colloidal forces between
      the prepared asphaltene films in aqueous solutions were measured with AFM to shed
      light on the stabilization of water or oil droplets coated with asphaltene films.
      Factors such as solution pH, KCl concentration, calcium addition, and temperature
      all showed a strong impact on colloidal forces between the prepared asphaltene
      films. The findings provided a better understanding of asphaltene interfacial
      films at an oil/water interface in stabilizing bitumen-in-water and water-in
      bitumen emulsions.

PMID- 16460067
TI  - Interaction between silicates and ionic surfactants in dilute solution.
AB  - Understanding the interaction between silicate ions and surfactants is critical
      for the design and development of mesoporous siliceous materials. We examined the
      interaction between sodium silicate ions and three different cationic surfactants
      [namely, cetyltrimethylammonium bromide (CTAB), tetradecyltrimethylammonium
      bromide (TTAB), and dodecyltrimethylammonium bromide (DTAB)] and an anionic
      surfactant [sodium dodecyl sulfate (SDS)] in dilute solution at room temperature.
      From the combination of several techniques, such as conductometric and
      potentiometric titrations, dynamic light scattering, and isothermal titration
      calorimetry, the phase behavior of the sodium silicate and CTAB system was
      determined. We observed that the aggregation behavior of the silicate-CTAB system
      is similar to that of a polymer-surfactant system. The formation of the silicate
      CTAB complex is induced by the adsorption of SiOH and SiO- groups, aided by CTAB
      unimers. The electrostatic attraction and hydrophobic interaction are the
      dominant forces controlling the formation of silicate-CTAB complexes. When these
      complexes are saturated with CTAB unimers, free CTAB micelles are then produced.
      TEM micrographs revealed that a stable Si-O-Si network is absent within the
      silicate-CTAB complexes, and surprisingly, stable silicate-CTAB complexes with
      ordered structure were observed. The present finding is important for
      understanding the interaction between silicate and surfactant in the synthesis of
      mesoporous structure in the dilute solution regime.

PMID- 16460068
TI  - Complementary use of simulations and molecular-thermodynamic theory to model
      micellization.
AB  - Molecular-thermodynamic descriptions of micellization in aqueous media can be
      utilized to model the self-assembly of surfactants possessing relatively simple
      chemical structures, where it is possible to identify a priori what equilibrium
      position they will adopt in the resulting micellar aggregate. For such chemical
      structures, the portion of the surfactant molecule that is expected to be exposed
      to water upon aggregate self-assembly can be identified and used as an input to
      the molecular-thermodynamic description. Unfortunately, for many surfactants
      possessing more complex chemical structures, it is not clear a priori how they
      will orient themselves within a micellar aggregate. In this paper, we present a
      computational approach to identify what portions of a surfactant molecule are
      hydrated in a micellar environment through the use of molecular dynamics
      simulations of such molecules at an oil/water interface (modeling the micelle
      core/water interface). The local environment of each surfactant segment is
      determined by counting the number of contacts of each segment with the water and
      oil molecules. After identifying the hydrated and the unhydrated segments of the
      surfactant molecule, molecular-thermodynamic modeling can be performed to
      predict: (i) the free-energy change associated with forming a micellar aggregate,
      (ii) the critical micelle concentration (CMC), and (iii) the optimal shape and
      size of the micellar aggregate. The computer simulation results were found to be
      sensitive to the atomic charge parameters utilized during the simulation runs.
      Two different methods of assigning atomic charges were tested, and the computer
      simulation and molecular-thermodynamic modeling results obtained using both sets
      of atomic charges are presented and compared. The combined computer
      simulation/molecular-thermodynamic modeling approach presented here is validated
      first by implementing it in the case of anionic (sodium dodecyl sulfate, SDS),
      cationic (cetyltrimethylammonium bromide, CTAB), zwitterionic
      (dodecylphosphocholine, DPC), and nonionic (dodecyl poly(ethylene oxide), C12E8)
      surfactants possessing relatively simple chemical structures and verifying that
      good predictions of CMCs and micelle aggregation numbers are obtained. In the
      case of C12E8, the challenges and limitations associated with simulating a
      single, polymeric E8 moiety at the oil/water interface to model its behavior at
      the micelle/water interface are discussed. Subsequently, the combined modeling
      approach is implemented in the case of the anionic surfactant 3-hydroxy sulfonate
      (AOS) and of the nonionic surfactant decanoyl-n-methylglucamide (MEGA-10), which
      possess significantly more complex chemical structures. The good predictions
      obtained for these two surfactants indicate that the combined computer
      simulation/molecular-thermodynamic modeling approach presented here extends the
      range of applicability of molecular-thermodynamic theory to allow modeling of the
      micellization behavior of surfactants possessing more complex chemical
      structures.

PMID- 16460069
TI  - Experimental and theoretical investigation of the micellar-assisted
      solubilization of ibuprofen in aqueous media.
AB  - Surfactants can be used to increase the solubility of poorly soluble drugs in
      water and to increase drug bioavailability. In this article, the aqueous
      solubilization of the nonsteroidal, antiinflammatory drug ibuprofen is studied
      experimentally and theoretically in micellar solutions of anionic (sodium dodecyl
      sulfate, SDS), cationic (dodecyltrimethylammonium bromide, DTAB), and nonionic
      (dodecyl octa(ethylene oxide), C12E8) surfactants possessing the same hydrocarbon
      "tail" length but differing in their hydrophilic headgroups. We find that, for
      these three surfactants, the aqueous solubility of ibuprofen increases linearly
      with increasing surfactant concentration. In particular, we observed a 16-fold
      increase in the solubility of ibuprofen relative to that in the aqueous buffer
      upon the addition of 80 mM DTAB and 80 mM C12E8 but only a 5.5-fold solubility
      increase upon the addition of 80 mM SDS. The highest value of the molar
      solubilization capacity (chi) was obtained for DTAB (chi = 0.97), followed by
      C12E8 (chi = 0.72) and finally by SDS (chi = 0.23). A recently developed computer
      simulation/molecular-thermodynamic modeling approach was extended to predict
      theoretically the solubilization behavior of the three ibuprofen/surfactant
      mixtures considered. In this modeling approach, molecular-dynamics (MD)
      simulations were used to identify which portions of ibuprofen are exposed to
      water (hydrated) in a micellar environment by simulating a single ibuprofen
      molecule at an oil/water interface (modeling the micelle core/water interface).
      On the basis of this input, molecular-thermodynamic modeling was then implemented
      to predict (i) the micellar composition as a function of surfactant
      concentration, (ii) the aqueous solubility of ibuprofen as a function of
      surfactant concentration, and (iii) the molar solubilization capacity (chi). Our
      theoretical results on the solubility of ibuprofen in aqueous SDS and C12E8
      surfactant solutions are in good agreement with the experimental data. The
      ibuprofen solubility in aqueous DTAB solutions was somewhat overpredicted because
      of challenges associated with accurately modeling the strong electrostatic
      interactions between the anionic ibuprofen and the cationic DTAB. Our results
      indicate that computer simulations of ibuprofen at a flat oil/water interface can
      be used to obtain accurate information about the hydrated and the unhydrated
      portions of ibuprofen in a micellar environment. This information can then be
      used as input to a molecular-thermodynamic model of self-assembly to successfully
      predict the aqueous solubilization behavior of ibuprofen in the three surfactant
      systems studied.

PMID- 16460070
TI  - Binding of sodium dodecyl sulfate with linear and branched polyethyleneimines in
      aqueous solution at different pH values.
AB  - Isothermal titration microcalorimetry (ITC), conductivity, and turbidity
      measurements have been carried out to study the interaction of sodium dodecyl
      sulfate (SDS) with polyethyleneimines (PEI) including linear PEI and branched PEI
      at different pH values of 3, 7, and 10. In all cases, the polymers show a
      remarkable affinity toward SDS. At pH 3, the polymer PEI is a strong polycation,
      and the binding is dominated by electrostatic 1:1 charge neutralization with the
      anionic surfactant. At pH 7, the electrostatic attraction between SDS and PEI is
      weak, and the hydrophobic interaction becomes stronger. At the natural pH of 10,
      PEI is essentially nonionic and binds SDS in the form of polymer-bound surfactant
      aggregates. The charge neutralization concentration (C1) of SDS for the PEI-SDS
      complex can be derived from the curves of variation of the enthalpy,
      conductivity, and turbidity with SDS concentration. There is good agreement
      between the results from the three methods and all show a decrease with
      increasing pH. The total interaction enthalpies (deltaH(total)) of PEI with SDS
      are obtained from the observed enthalpy curves and the difference enthalpy
      (deltaH*) between the total enthalpy of branched PEI with SDS, and the total
      enthalpy of linear PEI with SDS can be derived from the obtained deltaH(total).
      The difference deltaH* increases dramatically as pH increases, which indicates
      that the interactions are different for linear PEI and branched PEI at high pH
      values. A schematic map of the different states of aggregation is presented.

PMID- 16460071
TI  - Boltzmann distributions and slow relaxation in systems with spherical and
      cylindrical micelles.
AB  - Equilibrium and nonequilibrium distributions of molecular aggregates in a
      solution of a nonionic surfactant are investigated at the total surfactant
      concentration above the second critical micelle concentration (CMC2). The
      investigation is not limited by the choice of a specific micellar model.
      Expressions for the direct and reverse fluxes of molecular aggregates over the
      potential humps of the aggregation work are derived. These aggregation work humps
      set up activation barriers for the formation of spherical and cylindrical
      micelles. With the aid of the expressions for molecular aggregate fluxes, a set
      of two kinetic equations of micellization is derived. This set, along with the
      material balance equation, describes the molecular mechanism of the slow
      relaxation of micellar solution above the CMC2. A realistic situation has been
      analyzed when the CMC2 exceeds the first critical micelle concentration, CMC1, by
      an order of magnitude, and the total surfactant concentration varies within the
      range lying markedly above the CMC2 but not by more than 2 orders of magnitude.
      For such conditions, an equation relating the parameters of the aggregation work
      of a cylindrical micelle to the observable ratio of the total surfactant
      concentration and the monomer concentration is found for an equilibrium solution.
      For the same conditions, but in the nonequilibrium state of materially isolated
      surfactant solution, a closed set of linearized relaxation equations for total
      concentrations of spherical and cylindrical micelles is derived. These equations
      determine the time development of two modes of slow relaxation in micellar
      solutions markedly above the CMC2. Solving the set of equations yields two rates
      and two times of slow relaxation.

PMID- 16460072
TI  - Rheology of high internal phase emulsions.
AB  - The mechanical dispersion technology used in this study employs rotor-stator
      mixers that produce water-continuous high internal phase emulsions (HIPEs) with
      narrow drop size distributions and small drop sizes, even when the internal phase
      (oil) viscosity is quite high. Analysis of these HIPEs reveals trends that are
      consistent with formation by a capillary instability mechanism in which a shear
      deformation produces highly elongated drops that rupture to form uniform, small
      droplets. In the search for a predictive tool to aid in the manufacture and use
      of HIPEs, rheology data for these shear-thinning HIPEs have been compared to data
      for models in the literature. Existing models do not correctly account for the
      effect of a high internal phase viscosity on the rheological properties of the
      HIPE. Another shortcoming is failure to correctly address the shear-thinning
      exponent. Whereas internal phase viscosity does not seem to affect the shear
      thinning exponent, the surfactant apparently plays an important role, possibly
      through its modification of the interfacial tension and continuous phase
      rheology.

PMID- 16460073
TI  - Influence of interfacial characteristics on Ostwald ripening in hydrocarbon oil
      in-water emulsions.
AB  - The influence of the nature of the interfacial membrane on the kinetics of
      droplet growth in hydrocarbon oil-in-water emulsions was investigated. Droplet
      growth rates were determined by measuring changes in the droplet size
      distribution of 1 wt % n-tetradecane or n-octadecane oil-in-water emulsions using
      laser diffraction. The interfacial properties of the droplets were manipulated by
      coating them with either an SDS layer or with an SDS-chitosan layer using an
      electrostatic deposition method. The emulsion containing SDS-coated octadecane
      droplets did not exhibit droplet growth during storage for 400 h, which showed
      that it was stable to Ostwald ripening because of this oils extremely low water
      solubility. The emulsion containing SDS-coated n-tetradecane droplets showed a
      considerable increase in mean droplet size with time, which was attributed to
      Ostwald ripening associated with this oils appreciable water-solubility. On the
      other hand, an emulsion containing SDS-chitosan coated n-tetradecane droplets was
      stable to droplet growth, which was attributed to the ability of the interfacial
      membrane to resist deformation because of its elastic modulus and thickness. This
      study shows that the stability of emulsion droplets to Ostwald ripening can be
      improved by using an electrostatic deposition method to form thick elastic
      membranes around the droplets.

PMID- 16460074
TI  - Shamrock surfactants with terminal carboxylate headgroups and a central
      phosphorodithioate or quaternary ammonium headgroup.
AB  - Surfactants 3 (tripotassium O,O'-di-[11-(carboxylato)undecyl]phosphorodithioate)
      and 4 (sodium 12-[dimethyl-(11-carboxylatoundecyl)ammonio]dodecanoate), which are
      new shamrock surfactants, were prepared and characterized. Shamrock surfactants
      represent a novel class of surfactants that contain a central headgroup connected
      to two flanking headgroups by hydrocarbon chains; they do not contain long-chain
      alkyl groups. Surfactants 3 and 4 were characterized in water by measurement of
      their Krafft temperatures and critical aggregation concentrations, and their
      aggregates were studied by 1H and 31P NMR spectroscopy, dynamic laser light
      scattering, and phase-contrast optical microscopy. Aqueous 3 and 4 were also
      studied by cryoetch high-resolution scanning electron microscopy, which revealed
      fences with interposed lacelike patterns for the former and compartments formed
      by irregular fences for the latter. Coacervates were likely formed upon the
      undisturbed hydration of 3 and 4, as determined by phase-contrast optical
      microscopy.

PMID- 16460075
TI  - Self-assembled monolayers of alkanethiols on gold prepared in a hexagonal
      lyotropic liquid crystalline phase of Triton X-100/water system.
AB  - In this paper, we have reported a new method of preparing self-assembled
      monolayers (SAMs) of decanethiol and hexadecanethiol on gold surface by using a
      lyotropic liquid crystalline phase as an adsorbing medium. The stability and
      blocking ability of these SAMs were characterized using grazing angle Fourier
      transform infrared (FTIR) spectroscopy and electrochemical techniques such as
      cyclic voltammetry and electrochemical impedance spectroscopy. The lyotropic
      liquid crystalline medium possesses a hexagonal structure consisting of a
      nonionic surfactant Triton X-100, water, and the corresponding thiol, which
      provides a highly hydrophobic environment to solubilize the alkanethiols and
      later to facilitate their delivery to the gold surface. We find that the SAMs
      formed from the hexagonal liquid crystalline phase are highly compact and have
      excellent electrochemical blocking ability towards the redox probes compared to
      conventional SAMs prepared from commonly used organic solvents such as ethanol.
      From the impedance studies, we have determined the capacitance of the monolayer
      coated electrodes and the surface coverage of the SAM, which has been found to be
      >99.98% on gold surface. We have also estimated the extent of ionic permeability
      through the film and measured the rate constants for the redox reactions on the
      SAM-modified electrodes. Our results show that the rate constants of [Fe(CN)6](3
      /4-) and [Ru(NH3)6](2+/3+) redox couples are very much lower in the case of
      monolayers prepared in liquid crystalline phase compared to the SAM formed in 1
      mM thiol in ethanol solution, suggesting a better blocking ability of the SAMs in
      the former case. From the grazing angle FTIR spectroscopic studies and
      capacitance measurements, we have ruled out any coadsorption of surfactant
      molecules on the Au surface. These results suggest that SAMs of very low defect
      density and extremely low ionic permeability can be obtained when a hexagonal
      lyotropic liquid crystalline phase is used as an adsorbing medium.

PMID- 16460076
TI  - Molecular organization of an amphiphilic styryl pyridinium dye in monolayers at
      the air/water interface in the presence of various anions.
AB  - Amphiphilic 4-(3',4'-dimethoxystyryl)-N-octadecylpyridinium perchlorate and
      bromide form stable monolayers at the air/water interface. Small differences in
      the surface pressure-area and surface potential-area isotherms depending on the
      anion indicate interactions between the chromophore and the anions on the pure
      water subphase. The monolayer behavior is considerably modified on 10 mM aqueous
      solutions of KI, KClO4, KCl, and KF as revealed by isotherm measurements,
      reflection spectroscopy, and Brewster angle microscopy. The phase transition
      observed in the isotherms is shifted to higher surface pressure because of
      variation of the salt according to the Hofmeister series. Upon monolayer
      compression, the chromophores are increasingly tilted, and a shift of the band to
      longer wavelengths is attributed to the environment becoming less polar. However,
      in the case of KCl at small areas per molecule, relaxation is observed at
      constant area with the appearance of a new band shifted to shorter wavelengths.
      This band is assigned to small associates of about four chromophores (H
      aggregates). In the case of KI, a new band shifted to longer wavelengths is
      found. Theoretical calculations did not yield a transition in the observed range,
      even for large aggregates (J aggregates). Therefore, other interactions may be
      responsible for the appearance of this band.

PMID- 16460077
TI  - On the quasi-static relaxation of a drop in a combined model of dissipation.
AB  - The spontaneous quasi-static relaxation of liquid drops on solid surfaces in the
      partial wetting regime is studied. We base our study on the combined approach
      suggested in de Ruijter et al. (Langmuir 1999, 15, 2209), which uses the standard
      mechanical description of dissipative system dynamics. Two types of dissipation
      are considered: a hydrodynamic dissipation in the core of the droplet and a
      dissipation term proportional to the contact line length. In the case of the
      spherical cap approximation of the drop shape, we derive asymptotic solutions of
      the differential equations describing the base radius and the contact angle
      relaxation. The asymptotic solutions are derived by a perturbation technique for
      small initial deviations of the base radius from the final equilibrium value. We
      find that the time relaxation of the base radius and the cosine of the contact
      angle are given by a linear combination of exponential functions. We compare the
      asymptotic solutions with numerically obtained solutions, and we find very good
      agreement for small initial deviations. For larger initial deviations, the
      numerical solutions are well approximated by exponential decay functions of first
      or second order.

PMID- 16460078
TI  - Influence of an amide group in methyl octadecanoates on the monolayer stability.
AB  - The influence of a hydrogen bond donor and acceptor in the hydrophobic part of an
      amphiphile on the monolayer stability at the air/water interface is investigated.
      For that purpose, the amide group is integrated into the alkyl chain. Eight
      methyl octadecanoates have been synthesized with the amide group in two
      orientations and in different positions of the alkyl chain, namely, CH3O2C(CH2)m
      NHCO(CH2)n CH3 (n + m = 14): 1 (m = 1), 3 (m = 2), 5 (m = 3), 7 (m = 14); and
      CH3O2C(CH2)m CONH(CH2)n CH3: 2 (m = 1), 4 (m = 2), 6 (m = 3), 8 (m = 14). The
      monolayers have been characterized by their pi/A isotherms, their temperature
      dependence and Brewster angle microscopy (BAM). Amphiphile 1 with the amide group
      close to the ester group (m = 1) behaves like an unsubstituted fatty acid ester,
      while 3, 5, and 7, with the amide group in an intermediate and terminal position,
      exhibit a two-phase region. The amphiphiles 2, 4, 6, and 8, with a reversed
      orientation of the amide group, all exhibit a two-phase region with higher
      plateau pressures and lower collapse pressures than those of 1, 3, 5, and 7. For
      7 and 8, domains of the liquid condensed (LC) phase are visualized by BAM in the
      two-phase region. The liquid expanded (LE)/LC-phase transitions are all
      exothermic with enthalpies deltaH ranging from -31 to -12 kJ/mol. Comparison with
      other bipolar amphiphiles indicates that the LC phase is better stabilized by the
      hydroxy and dihydroxy groups than by the amide group. For model compounds of 1-4,
      optimized conformers in the LE and LC phases have been determined by density
      functional theory (DFT) calculations.

PMID- 16460079
TI  - Mean-field theory of liquid droplets on roughened solid surfaces: application to
      superhydrophobicity.
AB  - We present calculations of the density distributions and contact angles of liquid
      droplets on roughened solid surfaces for a lattice gas model solved in a mean
      field approximation. For the case of a smooth surface, this approach yields
      contact angles that are well described by Young's equation. We consider rough
      surfaces created by placing an ordered array of pillars on a surface, modeling so
      called superhydrophobic surfaces, and we have made calculations for a range of
      pillar heights. The apparent contact angle follows two regimes as the pillar
      height increases. In the first regime, the liquid penetrates the interpillar
      volume, and the contact angle increases with pillar height before reaching a
      constant value. This behavior is similar to that described by the Wenzel equation
      for contact angles on rough surfaces, although the contact angles are
      underestimated. In the second regime, the liquid does not penetrate the
      interpillar volume substantially, and the contact angle is independent of the
      pillar height. This situation is similar to that envisaged in the Cassie-Baxter
      equation for contact angles on heterogeneous surfaces, but the contact angles are
      overestimated by this equation. For larger pillar heights, two states of the
      droplet can be observed, one Wenzel-like and the other Cassie-like.

PMID- 16460080
TI  - Dielectric force and relative motion between two spherical particles in
      electrophoresis.
AB  - When two particles close to each other are in electrophoretic motion, each
      particle is under the influence of the nonuniform electric field generated by the
      other particle. Two particles may attract or repel each other due to the
      dielectric force, depending on their positions in the nonuniform electric field.
      In this work, the dielectric interaction and the subsequent relative motion of
      the two arbitrarily oriented spherical particles are analyzed. The dielectric
      force is obtained by integrating the Maxwell stress. The result is valid for
      arbitrary orientations of the particles under the thin electrical-double-layer
      assumption. The magnitude of the dielectric force is compared to the so-called
      inertia-induced force, which shows that the dielectric force is normally much
      greater than the inertia-induced force. The relative velocity of particles is
      determined by the force balance between the dielectric force and the Stokes drag.
      The regions of attraction and repulsion are defined. It is shown that a pair of
      particles eventually aligns parallel to the externally applied electric field,
      except in the case where the two particles are initially oriented perpendicular
      to the electric field. A closed-form analytical solution is obtained for the
      particle trajectory by using the approximate expression for the dielectric force
      valid for not-too-closely located particles.

PMID- 16460081
TI  - Physically self-assembled monolayers (PSAMs) of lecithin lipids at hydrophilic
      silicon oxide interfaces.
AB  - A new method of making physically self-assembled monolayers (PSAMs) on
      hydrophilic solid surfaces is presented. This method uses a mixture of a nonpolar
      solvent, such as hexane, and a strong polar solvent, such as ethanol, to dissolve
      the lipids. The deposition of two lecithin lipids, dipalmitoylphosphatidylcholine
      (DPPC) and dilauroylphosphatidylcholine (DLPC), has been studied. These lipids
      physically self-assemble, or adsorb, onto hydrophilic silicon oxide/silicon
      surfaces when such surfaces are in contact with the lipid solution. The adsorbed
      layers were probed with ex-situ attenuated total reflection infrared (ATR-IR)
      spectroscopy, ellipsometry, contact angle measurements, and atomic force
      microscopy (AFM). The thicknesses of the adsorbed monolayers are about 2.8 +/-
      0.2 nm for DPPC and 2.0 +/- 0.2 nm for DLPC, as determined by ellipsometry and
      AFM. Smooth, uniform monolayers of controlled surface density are formed. The
      surface density of adsorbed layers is comparable to those of close-packed lipid
      monolayers, as calculated from the ellipsometry and ATR-IR results. Producing
      controlled-thickness monolayers has applications in boundary lubrication,
      biomaterials, sensor technologies, and electronics. The method can be used for
      depositing many biological surfactants or lipids without the need to modify these
      surfactants chemically to form chemical bonds with the surfaces, as required by
      the usual chemical SAMs. Moreover, the new method has several advantages compared
      to the Langmuir-Blodgett (LB) method.

PMID- 16460082
TI  - Synthesis and surface properties of new ureas and amides at different interfaces.
AB  - The influence of the urea and amide group in the alkyl chain of methyl
      nonadecanoate on the surface properties is investigated and compared. For that
      purpose, the ureas CH3O2C-(CH2)m-NHCONH-(CH2)n-CH3 (n + m = 14) [1 (m = 2), 3 (m
      = 3), and 5 (m = 4)] and the amides CH3O2C-(CH2)m-NHCO-(CH2)n-CH3 (n + m = 15)
      [2(m = 2), 4 (m = 3), and 6 (m = 4)] were synthesized. The pi/A isotherms of the
      ureas show up to the attainable temperature of 313 K no LE phase, which indicates
      a very stable LC phase. The amides exhibit a two phase plateau region, with the
      exception of 2. The different behavior is connected with the hydrogen bond
      energies, which are stronger with the ureas in the LC than in the LE phase,
      whereas those of the amides have a similar strength in both phases. The effect of
      hydrogen bonds in self-assembled molecules of N,N'-dialkylurea CH3-(CH2)m-NHCONH
      (CH2)n-CH3 (m + n = 14) [7 (n = 2)] was visualized by STM at the
      octylbenzene/graphite interface. Compound 7 forms a lamella structure with a
      periodicity of one molecule length. The tilt angle of 86 degrees +/- 2 degrees to
      the edge of the lamella points to a nearly orthogonal arrangement of the
      molecules. It indicates two equivalent bonds between the aza-hydrogens and the
      carbonyl oxygen. A similar arrangement is proposed for the LC phase of the ureas
      at the air/water interface.

PMID- 16460083
TI  - Novel fabrication of Ag thin film on glass for efficient surface-enhanced Raman
      scattering.
AB  - This paper describes a very simple electroless-plating method used to prepare
      optically tunable nanostructured Ag films. Very stable Ag films can be
      reproducibly fabricated simply by soaking glass substrates in ethanolic solutions
      of AgNO3 and butylamine. The grain size of silver can be readily controlled to
      range from 20 to 150 nm, and these nanostructural features correlated well with
      their UV/vis absorption characteristics, as well as with their surface-enhanced
      Raman scattering (SERS) activities. It is also very advantageous that the Ag
      films prepared exhibit very even SERS activity over an area up to hundreds
      thousand square-micrometers, and the enhancement factor estimated using
      benzenethiol as a prototype adsorbate reaches approximately 2 x 10(5). Since the
      proposed method is cost-effective and is suitable for the mass production of
      diverse Ag films irrespective of the shapes of the underlying substrates, it is
      expected to play a significant role in the development of surface plasmon-based
      analytical devices.

PMID- 16460084
TI  - Formation of helical J-aggregate of chiral thioether-derivatized phthalocyanine
      bound by palladium(II) at the toluene/water interface.
AB  - A chiral thioether-substituted phthalocyanine ((2,3,9,10,16,17,23,24-octakis-1
      phenylethylthiophthalocyaninato)magnesium(II) [MgPc(SEtPh)8]) has been
      synthesized, which can be bound by soft-metal ions such as palladium(II) ion.
      Aggregates formed from MgPc(SEtPh)8 and Pd(II) in toluene and at the
      toluene/water interface were characterized by means of UV-vis absorption and
      circular dichroism (CD) spectrometries using centrifugal liquid-membrane (CLM)
      cell. Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF/MS) and scanning electron microscope (SEM) were used as
      complementary techniques. The toluene solution of MgPc(SEtPh)8 had no optical
      chirality. However, the addition of PdCl2 into the toluene solution of
      MgPc(SEtPh)8 induced optical chirality, which indicated the formation of a
      twisted H-type dimer (face-to-face fashion) of MgPc(SEtPh)8 bound by four PdCl2
      in the bulk toluene solution. On the other hand, in the toluene/water interface,
      helical J-aggregate (head-to-tail fashion) of MgPc(SEtPh)8 bound by PdCl2 was
      formed, in which one J-aggregate unit contained five 1:2 complexes of
      MgPc(SEtPh)8-Pd(II) on average. On the basis of the experimental results and the
      exciton theory for optical chirality, a possible mechanism for the chiral
      aggregation of MgPc(SEtPh)8-Pd(II) complexes at the interface was proposed. In
      the present study, we demonstrated a novel strategy for the design of helical
      phthalocyanine aggregates using the liquid/liquid interface as a template.

PMID- 16460085
TI  - Nanoengineered multiscale hierarchical structures with tailored wetting
      properties.
AB  - A simple method for fabricating micro/nanoscale hierarchical structures is
      presented using a two-step temperature-directed capillary molding technique. This
      lithographic method involves a sequential application of the molding process in
      which a uniform polymer-coated surface is molded with a patterned mold by means
      of capillary force above the glass transition temperature of the polymer. Various
      microstructures and nanostructures were fabricated with minimum resolution down
      to approximately 50 nm with good reproducibility. Also contact angle measurements
      of water indicated that two wetting states coexist on a multiscale hierarchical
      structure where heterogeneous wetting is dominant for the microstructure and
      homogeneous wetting for the nanostructure. A simple theoretical model combining
      these two wetting states was presented, which was in good agreement with the
      experimental data. Using this approach, multiscale hierarchical structures for
      biomimetic functional surfaces can be fabricated with precise control over
      geometrical parameters and the wettability of a solid surface can be tailored in
      a controllable manner.

PMID- 16460086
TI  - Nylon surface modification: 2. Nylon-supported composite films.
AB  - We have developed techniques for the introduction of reactive functional groups
      to nylon surfaces via site-specific reactions targeting at the naturally abundant
      amide repeating units on the surface. In this report, we describe the fabrication
      of nylon-supported composite surfaces using the most efficient modification
      methods we have developed. N-Alkylation with (3-glycidoxypropyl)triethoxysilane
      (GPTES) in the presence of potassium tert-butoxide (t-BuOK) leads to surfaces
      with silica-like reactivity. Subsequent chemical vapor deposition using
      tetrachlorosilane (SiCl4) and water results in composite films with a thin layer
      of silica, which was made hydrophobic by reaction with a fluorinated silane
      reagent. Reduction of the amide groups with borane-THF (BH3-THF) complex leads to
      a 69% conversion of surface amides to the corresponding secondary amine groups.
      Alginate was chosen as the model polyelectrolyte for the introduction of a
      hydrated surface layer. Because of the strong electrostatic interaction between
      alginate and the amine-enriched nylon surfaces, the adsorption is fast and
      concentration-independent (within the concentration range studied). The
      polysaccharide coats the surface homogeneously, without the formation of large
      aggregates. The amine surfaces obtained by reduction with BH3-THF ((BH3-THF)nylon
      NH) and by alkylation with 2-bromoethylamine hydrobromide (BEA-HBr, (EBA
      HBr)nylon-NH2) were also used to study gold deposition through electroless
      plating. Immobilization of a negatively charged metal complex (AuCl4(-)) was
      achieved through electrostatic interaction. Gold particles disperse
      preferentially in the bulk of (EBA-HBr)nylon-NH2 films, while they remain
      confined to the outer surface layer of (BH3-THF)nylon-NH films.

PMID- 16460088
TI  - Preparation and characterization of thin films of SiO(x) on gold substrates for
      surface plasmon resonance studies.
AB  - We report here on the fabrication and characterization of stable thin films of
      amorphous silica (SiO(x)) deposited on glass slides coated with a 5 nm adhesion
      layer of titanium and 50 nm of gold, using the plasma-enhanced chemical vapor
      deposition (PECVD) technique. The resulting surfaces were characterized using
      atomic force microscopy (AFM), ellipsometry, contact angle measurements, and
      surface plasmon resonance (SPR). AFM analysis indicates that homogeneous films of
      silica with low roughness were formed on the gold surface. The deposited silica
      films showed excellent stability in different solvents and in piranha solution.
      There was no significant variation in the thickness or in the SPR signal after
      these harsh treatments. The Au/SiO(x) interfaces were investigated for their
      potential applications as new surface plasmon resonance sensor chips. Silica
      films with thicknesses up to 40 nm allowed visualization of the surface plasmon
      effect, while thicker films resulted in the loss of the SPR characteristics. SPR
      allowed further the determination of the silica thickness and was compared to
      ellipsometric results. Chemical treatment of the SiO(x) film with piranha
      solution led to the generation of silanol surface groups that have been coupled
      with a trichlorosilane.

PMID- 16460087
TI  - Adhesion of single polyelectrolyte molecules on silica, mica, and bitumen
      surfaces.
AB  - In a recent study (Energy Fuels 2005, 19, 936), a partially hydrolyzed
      polyacrylamide (HPAM) was used as a process aid to recover bitumen from oil sand
      ores. It was found that HPAM addition at the bitumen extraction step not only
      improved bitumen recovery but also enhanced fine solids settling in the tailings
      stream. To understand the role of HPAM, single-molecule force spectroscopy was
      employed for the first time to measure the desorption/adhesion forces of single
      HPAM molecules on silica, mica, and bitumen surfaces using an atomic force
      microscope (AFM). Silicon wafers with an oxidized surface layer and newly cleaved
      mica were used, respectively, to represent sand grains and clays in oil sands.
      The force measurements were carried out in deionized water and in commercial
      plant process water under equilibrium conditions. The desorption/adhesion forces
      of HPAM obtained on mica, silica, and bitumen surfaces were approximately 200,
      40, and 80 pN in deionized water and approximately 100, 50, and 40 pN in the
      plant process water, respectively. The measured adhesion forces together with the
      zeta potential values of these surfaces indicate that the polymer would
      preferentially adsorb onto clay surfaces rather than onto bitumen surfaces. It is
      the selective adsorption of HPAM that benefits both bitumen recovery and tailings
      settling when the polymer was added directly to the bitumen extraction process at
      an appropriate dosage.

PMID- 16460089
TI  - Optical microscope absorbance imaging of carbon black nanoparticle films at solid
      and liquid surfaces.
AB  - We have used an optical transmission microscope equipped with a digital camera
      and fitted with a narrow-band-pass filter to obtain absorbance images consisting
      of an array of pixel absorbance values. Absorbance images of films of carbon
      nanoparticles were used to derive spatially resolved images of the carbon film
      thicknesses with a resolution in the thickness dimension of a few nanometers. The
      technique was applied to the characterization of carbon nanoparticle films at
      cellulose-coated glass surfaces and at the oil-water interfaces of emulsion
      drops. For the emulsions, it was necessary to use oil and water phases of equal
      refractive index to avoid artifacts due to the drops acting as lenses.

PMID- 16460090
TI  - Sulfidation of lead-loaded zeolite microparticles and flotation by amylxanthate.
AB  - The possibility of recovering lead-loaded zeolite Y microparticles (PbY) by
      flotation after sulfidation was investigated using amyl xanthate (AMX) as the
      collector. The sulfidation process (by aqueous Na2S) was first studied as a
      function of the medium composition (Na2S concentration, pH), and the solid phases
      were characterized by various physicochemical techniques (X-ray photoelectron
      spectroscopy, high-frequency impedance measurements, and electrochemistry).
      Progressively increasing the sulfidation level resulted in the concomitant
      transformation of Pb(II) species ion-exchanged in the zeolite into PbS clusters
      that were mostly located at the external boundaries of the zeolite particles
      while remaining attached to the aluminosilicate (PbS-Y). Similar to what occurred
      for galena particles, the zeolite-supported PbS clusters were likely to adsorb
      the AMX collector, the remaining (nonsulfided) ion-exchanged Pb(II) species being
      transformed into a Pb(AMX)2 precipitate when using AMX in large excess. Owing to
      such AMX adsorption on PbS-Y, the zeolite particles were found to flocculate and
      to float in the presence of air bubbles. If rather high AMX concentrations (>5 x
      10(-3) M) were necessary to ensure the flotation of nonsulfided PbY particles
      (Walcarius, A.; Lamdaouar, A. M.; El Kacemi, K.; Marouf, B.; Bessiere, J.
      Langmuir 2001, 17, 2258), significantly lower concentrations (down to 1 x 10(-4)
      M) gave rise to high flotation yields (ca. 95%) upon PbY sulfidation. It is
      noteworthy that the sulfidation level should be maintained at a value high enough
      (>10%) to produce the minimal PbS amount ensuring flotation but not too high
      (<75%) to avoid conditions that are too reducing and are not compatible with the
      flotation process. Finally, depression tests seemed to indicate that PbS-Y
      flotation occurs according to a mechanism similar to that described for the
      galena mineral.

PMID- 16460091
TI  - Characterization of a novel water-soluble 3,4,9,10-perylenetetracarboxylic
      diimide in solution and in self-assembled zirconium phosphonate thin films.
AB  - The properties of N,N'-bis(2-phosphonoethyl)-3,4,9,10-perylenetetracarboxylic
      diimide (PPDI), a water-soluble perylene dye, have been studied in solution and
      in thin films. Absorption spectra showed that PPDI exists in the monomeric form
      in water/ethanol (1:1) and water/dimethyl sulfoxide (DMSO) (3:7) mixtures, but
      forms dimers in water and higher aggregates in ethanol. The PPDI monomer is
      highly fluorescent, in contrast to the dimers and aggregates, which are
      nonfluorescent. The monomer/dimer equilibrium was conveniently followed in a
      water/ethanol (7:3) mixture by varying the dye concentration. An equilibrium
      constant of K = 1.25 x 10(5) M(-1) was estimated for the dimerization process in
      this solvent mixture. The addition of cetyl trimethylammonium bromide (CTAB), a
      cationic surfactant, to aqueous solutions of PPDI resulted in the dissociation of
      the dimers, showing that the dye was incorporated into the micellar phase. Self
      assembled thin films of PPDI were grown on both silica gel particles and flat
      surfaces, using zirconium phosphonate chemistry. The growth of multilayered films
      on flat surfaces was monitored by ellipsometry (silicon substrates) and UV/Vis
      spectroscopy (quartz slides), and was linear with the number of deposition
      cycles. No fluorescence was detected from the PPDI films, and the absorption
      spectra of the films were quite similar to the spectrum of the compound in
      ethanol, indicating that the dye molecules were stacked in the films. Mixed
      monolayers containing PPDI and N,N'-bis(2-phosphonoethyl)-1,4,5,8
      naphthalenediimide (PNDI) on quartz were also prepared. Monolayers obtained by
      codeposition from solutions containing both PPDI and PNDI were richer in PPDI,
      even when the solution contained a large excess of the naphthalene derivative,
      showing that pi-stacking of PPDI is an important driving force in the formation
      of the films.

PMID- 16460092
TI  - Optimum conditions for adsorptive storage.
AB  - The storage of gases in porous adsorbents, such as activated carbon and carbon
      nanotubes, is examined here thermodynamically from a systems viewpoint,
      considering the entire adsorption-desorption cycle. The results provide concrete
      objective criteria to guide the search for the "Holy Grail" adsorbent, for which
      the adsorptive delivery is maximized. It is shown that, for ambient temperature
      storage of hydrogen and delivery between 30 and 1.5 bar pressure, for the optimum
      adsorbent the adsorption enthalpy change is 15.1 kJ/mol. For carbons, for which
      the average enthalpy change is typically 5.8 kJ/mol, an optimum operating
      temperature of about 115 K is predicted. For methane, an optimum enthalpy change
      of 18.8 kJ/mol is found, with the optimum temperature for carbons being 254 K. It
      is also demonstrated that for maximum delivery of the gas the optimum adsorbent
      must be homogeneous, and that introduction of heterogeneity, such as by ball
      milling, irradiation, and other means, can only provide small increases in
      physisorption-related delivery for hydrogen. For methane, heterogeneity is always
      detrimental, at any value of average adsorption enthalpy change. These results
      are confirmed with the help of experimental data from the literature, as well as
      extensive Monte Carlo simulations conducted here using slit pore models of
      activated carbons as well as atomistic models of carbon nanotubes. The
      simulations also demonstrate that carbon nanotubes offer little or no advantage
      over activated carbons in terms of enhanced delivery, when used as storage media
      for either hydrogen or methane.

PMID- 16460093
TI  - Surface-pressure isotherms of monolayers formed by microsize and nanosize
      particles.
AB  - The thermodynamic model of a 2D solution developed earlier for protein monolayers
      at liquid interfaces is generalized for monolayers composed of micro- and
      nanoparticles. Surface pressure isotherms of particle monolayers published in the
      literature for a wide range of particles sizes (between 75 microm and 7.5 nm) are
      described by the theoretical model with one modification. The calculations of
      surface pressure pi on area A provide satisfactory agreement with the
      experimental data. The theory also yields reasonable cross-sectional area values
      of the solvent molecule water in the range between 0.12 and 0.18 nm2, which is
      almost independent of particle size. Also, the area per particle in a closely
      packed monolayer obtained from the theory is quite realistic.

PMID- 16460094
TI  - In-situ FTIR studies on self-assembled monolayers of surfactant molecules
      adsorbed on H-terminated Si(111) surfaces in aqueous solutions.
AB  - The adsorption of a surfactant, sodium di-2-ethylhexyl sulfosuccinate (SDES),
      [C4H9CH(C2H5)CH2OCO][C4H9CH(C2H5)CH2OCOCH2]CHSO3- Na+, in an aqueous solution on
      an atomically flat H-terminated Si(111) [abbreviated as H-Si(111)] surface with a
      hydrophobic property was investigated by in-situ FTIR measurements. Immersion of
      the H-Si(111) surface in a solution of 1.0 x 10(-2) M SDES for more than 2 h led
      to formation of a self-assembled monolayer (SAM) with the alkyl chains having a
      tendency to be assembled perpendicular to the Si surface. The in-situ FTIR
      observation revealed that the adsorption was nearly complete about 60 min after
      the start of the immersion, and after that the adsorbed molecules changed their
      arrangement into an ordered mode. The Si-H peak in the FTIR spectrum remained
      unchanged with time in aqueous surfactant solution, in contrast to the case of
      immersion in pure water, indicating that the adsorbed surfactant protects the H
      Si(111) surface from oxidation. No structural change in the SAM was observed when
      a negative potential of -700 mV vs Ag/AgCl was applied to the Si, whereas the
      adsorbed molecules changed their arrangement, accompanied by their substantial
      desorption and oxidation of the Si surface, when a positive potential of +700 mV
      was applied.

PMID- 16460095
TI  - Designing for optimum liquid repellency.
AB  - In the current state-of-the-art, most super repellent surfaces are not
      sufficiently robust to move out of the laboratory into the commercial realm. With
      the hope of creating super repellent surfaces that could be employed in a wider
      variety of commercial applications, means to improve the robustness of
      ultralyophobic surfaces have been explored theoretically. Suspension pressures
      and drop retention forces were examined in terms of asperity shape, size, and
      spacing. The findings from this study suggest a strategy for creating surfaces
      that maintain their liquid repellency even after exposure to large hydrostatic
      pressures associated with liquid columns or jets.

PMID- 16460096
TI  - Ellipsometric search for vapor layers at liquid-hydrophobic solid surfaces.
AB  - We use precision ellipsometry to evaluate the existence of nanometer thick vapor
      films at the surface between a liquid and a hydrophobic alkylsilane coated Si
      wafer. We find no evidence for such vapor films. All of our fluid-solid
      ellipsometry measurements can be explained using a double layer model consisting
      of an oxide plus silane layer between the fluid and bulk Si substrate. We have
      carefully checked our ellipsometer for residual phase shifts which might, under
      certain circumstances, cause a mis-interpretation of the experimental results. We
      find that the most reliable ellipsometric results for thin films (which are
      relatively immune to the presence of small residual phase shifts) are collected
      at the Brewster angle. The dielectric constant of the native oxide coating is
      also compared with similar measurements for two thick (approximately 100-300 nm)
      thermally grown oxide coatings on a Si wafer.

PMID- 16460097
TI  - Why surfaces modified by flexible polymers often have a finite contact angle for
      good solvents.
AB  - Polymers adsorbing from a dilute solution onto the solvent-vapor interface
      generate a nonzero surface pressure. When the same polymers are end-grafted onto
      a surface such that a so-called polymer brush is formed, one will find that the
      solvent wets this compound interface partially. The partial wetting and the
      finite surface pressure are intimately linked properties of the polymer-solvent
      vapor combination. It is shown that the spreading parameter in the wetting
      problem is proportional to the surface pressure in the adsorption case. Complete
      wetting is only possible when this surface pressure is nonpositive. The wetting
      characteristics are hardly influenced by the grafting density and chain length
      characterizing the brush. We argue that the grafted polymer chains can bridge to
      the solvent-vapor interface, thereby preventing the wetting film to become
      macroscopically thick. We present experimental data underpinning our self
      consistent field analysis. Indeed, finite contact angles should be expected in
      various systems in which bridging attraction contributes to the disjoining
      pressure in wetting films.

PMID- 16460098
TI  - Encapsulation of polyanilines into graphite oxide.
AB  - Herein we report on the intercalation of polyaniline, poly(2-ethylaniline), and
      poly(2-propylaniline) into graphite oxide. This was achieved by taking advantage
      of the exfoliation/reconstruction properties of the layered host. The resulting
      intercalates were characterized by powder X-ray diffraction and thermogravimetric
      analysis.

PMID- 16460099
TI  - Raman and surface enhanced Raman microscopy of microstructured
      polyethylenimine/DNA multilayers.
AB  - We analyze microstructured multilayer films of poly(ethyleneimine) (PEI) and DNA
      by employing Raman and surface enhanced Raman spectroscopy (SERS). The
      microstructuring of the samples allows a simultaneous measurement of signal and
      reference in a single analytic process. Silver nanoparticles are implemented in
      the microstructured multilayers for SERS measurements. The recorded SERS spectra
      of PEI/DNA are dominated by the Raman bands of the DNA bases which show a larger
      mean enhancement than bands belonging to DNA backbone vibrations. Our results
      show that the combination of SERS and microstructured multilayer films provides
      an adapted way to characterize the polyelectrolytes as well as to measure the
      enhancement factor and the distance dependence for the SERS active silver
      nanoparticles. Furthermore, microstructured polyelectrolyte films containing SERS
      active nanoparticles are used for sensing molecules.

PMID- 16460100
TI  - Ultrafiltration membrane for electrophoretic capturing of pathogens for AFM
      imaging.
AB  - This communication describes a simple and rapid technique for electrophoretically
      assisted capture of phages, viruses, and other pathogens on the surface of an
      ultrafiltration membrane that can be considered smooth at the nanoscale. The
      surface was prepared by coating commercial dialysis membrane with a micrometer
      thick layer of cross-linked dextran or globular proteins. To ensure strong
      adherence of the coating, the surface of the dialysis membrane was activated in
      cold plasma. It was shown that the root-mean-square roughness of the coating was
      well below 1 nm when the polymer solution used for coating was allowed to slowly
      dry through a dialysis membrane left in direct contact with mica. Relatively
      small viral particles (e.g., fd phages 0.7 microm long and only 3.5 nm high in
      the dry state) are readily visible by AFM following electrophoretic capture from
      suspensions containing as few as 1 x 10(6) particles/mL onto membranes prepared
      as described.

PMID- 16460101
TI  - Nonlinearly additive forces in multivalent ligand binding to a single protein
      revealed with force spectroscopy.
AB  - We present evidence of multivalent interactions between a single protein molecule
      and multiple carbohydrates at a pH where the protein can bind four ligands. The
      evidence is based not only on measurements of the force required to rupture the
      bonds formed between concanavalin A (ConA) and alpha-D-mannose but also on an
      analysis of the polymer-extension force curves to infer the polymer architecture
      that binds the protein to the cantilever and the ligands to the substrate. We
      find that although the rupture forces for multiple carbohydrate connections to a
      single protein are larger than the rupture force for a single connection, they do
      not scale additively with increasing number. Specifically, the most common
      rupture forces are approximately 46, 68, and 85 pN at a loading rate of 650 +/-
      25 pN/s, which we argue corresponds to 1, 2, and 3 ligands being pulled
      simultaneously from a single protein as corroborated by an analysis of the
      linkage architecture. As in our previous work polymer tethers allow us to
      discriminate between specific and nonspecific binding. We analyze the binding
      configuration (i.e., serial vs parallel connections) through fitting the polymer
      stretching data with modified wormlike chain (WLC) models that predict how the
      effective stiffness of the tethers is affected by multiple connections. This
      analysis establishes that the forces we measure are due to single proteins
      interacting with multiple ligands, the first force spectroscopy study that
      establishes single-molecule multivalent binding unambiguously.

PMID- 16460102
TI  - Thermally reversible pluronic/heparin nanocapsules exhibiting 1000-fold volume
      transition.
AB  - Novel Pluronic/heparin composite nanocapsules that exhibit a thermally
      responsible swelling and deswelling behavior were synthesized. Pluronic F-127
      preactivated with p-nitrophenyl chloroformate at its two terminal hydroxyl groups
      was dissolved in a methylene chloride phase. The organic phase was dispersed in
      an aqueous phase containing heparin. At an organic/aqueous interface, Pluronic
      cross-linked heparin nanocapsules were produced. They exhibited a 1000-fold
      volume transition (ca. 336 nm at 25 degrees C; ca. 32 nm at 37 degrees C), and a
      reversible swelling and deswelling behavior when the temperature was cycled
      between 20 and 37 degrees C. The reversible volume transition of Pluronic
      nanocapsules was caused by micellization and demicellization of cross-linked
      Pluronic polymer chains within the nanocapsule structure in response to
      temperature. The morphological characters were investigated with transmission
      electron microscopy and small angle neutron scattering. Pluronic/heparin
      nanocapsules had an aqueous fluid-filled hollow interior with a surrounding shell
      layer below the critical temperature, but they became a collapsed core/shell
      structure similar to that of Pluronic micelles above it.

PMID- 16460103
TI  - Immobilization of antibodies on biosensing devices by nanoarrayed self-assembled
      monolayers.
AB  - This work presents an original and straightforward technique for antibody
      immobilization onto a surface, keeping the antibody in a biologically reactive
      configuration. Self-assembly of molecular monolayers and plasma-based colloidal
      lithography were combined to create chemical nanopatterns on the surface of a
      biosensing device. This technique was employed to create an array of 100 nm wide
      motifs having a hexagonal 2-D crystalline structure, characterized by COOH
      terminated nanospots in a CH3-terminated matrix. The quality control of the
      chemical nanopattern was carried out by combining atomic force microscopy,
      ellipsometry, and contact angle measurements. Enzyme-linked immunosorbent assay
      experiments were set up showing that the COOH/CH3 nanopatterned surface
      constrains the immobilization of the antibodies in a biologically reactive
      configuration, thus significantly improving the device performances as compared
      to those of more conventional nonpatterned COOH-terminated or CH3-terminated
      surfaces.

PMID- 16460104
TI  - Mapping the interaction forces between TAR RNA and TAT peptides on GaAs surfaces
      using chemical force microscopy.
AB  - The complexation of the HIV transactivation response element (TAR) RNA with the
      viral regulatory protein TAT is of enormous interest for the design of new
      sensing and therapeutic strategies. In this work, we anchored TAT peptides on
      GaAs surfaces using microcontact printing. Atomic force microscopy was used to
      quantify the interaction between TAR RNA and model TAT peptide sequences.
      Different pH conditions were utilized in order to assess specific vs nonspecific
      interactions. AFM tips functionalized with TAR RNA molecules were used to collect
      adhesion maps that displayed stronger interaction with peptide sequences that
      contained a greater number of arginine residues. All of the studies consistently
      showed a pH dependence of the interaction between the surface bound peptides and
      the TAR RNA on the AFM tips. This work quantifies the TAR RNA/TAT peptide
      interaction after one of the molecules is anchored on a surface. The conclusions
      in this paper are consistent with previous work and demonstrate that cationic
      residues are responsible for the polyelectrolyte-like affinity of TAT peptides
      for TAR RNA.

PMID- 16460105
TI  - Surface thermodynamics reveals selective structural information storage capacity
      of c-Fos-phospholipid interactions.
AB  - The surface properties of c-Fos, a regulator of normal and pathologic cell growth
      and a modulator of phospholipid metabolism, suggest that it has the potential to
      transduce information through molecular reorganization, placing the nature of its
      interaction with phospholipids at the basis of its possible effects at the
      membrane level. Previous studies established that c-Fos induces condensation and
      depolarization of PIP2 films and expansion and hyperpolarization of PC. We have
      now explored more in depth the thermodynamic aspects of these lipid-protein
      interactions, finding that the mixtures have associated hysteresis. The analysis
      of the excess thermodynamic functions provides evidence of entropic-enthalpic
      compensations that result in a favorable enthalpic contribution derived from the
      interaction of c-Fos with PIP2, which exceeds the unfavorable configurational
      entropy. On the contrary, favorable entropy terms dominate the interaction of c
      Fos with PC over the unfavorable enthalpy. The free energy of hysteresis is
      stored as excess free energy. A shift in molecular packing-dependent surface
      reorganization, compared to that of ideally mixed films, indicates a gain in
      information content at the lipid-protein interface in mixed films of c-Fos with
      PIP2 but not with PC. It is postulated that the free energy stored in these
      mixtures could act as a bidirectional structural information transducer for
      dynamic compression-expansion processes occurring on the membrane surface.

PMID- 16460106
TI  - Bioconjugation of Ln3+-doped LaF3 nanoparticles to avidin.
AB  - The binding of Eu3+-doped LaF3 nanoparticles with biotin moieties at the surface
      of the stabilizing ligand layer to avidin, immobilized on cross-linked aragose
      beads, is described. The biotin moieties were attached to the nanoparticles by
      reaction of an activated ester with the amino groups on the surface of the
      nanoparticles resulting from the 2-aminoethyl phosphate ligands that were
      coordinated to the surface through the phosphate end. This strategy of employing
      the reactions of amines with activated esters provides a general platform to
      modify the surface of the 2-aminophosphate stabilized Ln3+-doped LaF3
      nanoparticles with biologically relevant groups. Significant suppression of
      nonspecific binding to the avidin modified aragose beads has been realized by the
      incorporation of poly(ethylene glycol) units via the same reaction of a primary
      amine with an activated ester. The particle size distribution of the
      functionalized nanoparticles was within 10-50 nm, with a quantum yield of 19% in
      H2O for the LaF3 nanoparticles codoped with Ce3+ and Tb3+. A discreet, 4 unit
      poly(ethylene glycol) spaced heterobifunctional cross-linker, functionalized with
      biotin and N-hydroxysuccinimide at opposite termini, was covalently linked to the
      2-aminoethyl phosphate ligand via the N-hydroxysuccinimide activated ester,
      making an amide bond, imparting biological activity to the particle. Modification
      of the remaining unreacted amino groups of the stabilizing ligands was done with
      Me(OCH2CH2)3CH2CH2(C=O)-NHS (NHS = N-hydroxysuccinimide).

PMID- 16460107
TI  - Wetting of CVD carbon films by polar and nonpolar liquids and implications for
      carbon nanopipes.
AB  - The handling, dispersion, manipulation, and functionalization of carbon nanotubes
      and nanopipes often require the use of solvents. Therefore, a good understanding
      of the wetting properties of the carbon nanotubes is needed. Such knowledge is
      also essential for the design of nanotube-based nanofluidic devices, which hold
      the promise of revolutionizing chemical analysis, separation, drug delivery,
      filtration, and sensing. In this work, we investigated the wetting behavior of
      individual nanopipes produced by the chemical vapor deposition (CVD) of carbon in
      porous alumina templates and of thin carbon films produced by the same technique.
      The carbon pipes and films have the same chemistry and structure as determined by
      Raman and infrared spectroscopies and, when similarly treated, demonstrate the
      same qualitative wetting behavior, as determined by optical microscopy. Thus,
      measurements conducted on the carbon film surface are relevant to the nanopipes.
      In the case of the nanopipes, filling with various liquids was monitored. Contact
      angle experiments with both polar (water, glycerol, ethylene glycol, ethanol,
      tetra-hydro furan, and 2-propanol alcohol) and nonpolar liquids (cyclohexane,
      hexadecane, poly(dimethylsiloxane), and a fluoro-silicone) were conducted on
      films using the sessile drop method. The contact angles on the CVD carbon films
      ranged from 0 to 79 degrees. The exposure of the carbon films to a NaOH solution,
      typically used to dissolve the alumina template, led to a significant decrease of
      the contact angle, especially in the case of polar liquids.

PMID- 16460108
TI  - Positive-tone nanopatterning of chemical vapor deposited polyacrylic thin films.
AB  - Terpolymers of methyl alpha-chloroacrylate (MCA), methacrylic acid (MAA), and
      methacrylic anhydride (MAH) were synthesized by initiated chemical vapor
      deposition (iCVD) of MCA and MAA followed by low-temperature annealing that
      partially converts MAA into MAH. The MAA composition in the iCVD copolymer can be
      systematically varied between 37 and 85 mol % by adjusting the gas feed fractions
      of monomers. Study of the monomer reactivity ratios and the copolymer molecular
      weights supports the hypothesis of a surface propagation mechanism during the
      iCVD copolymerization. The carboxylic dehydration reaction at the annealing
      temperature of 160 degrees C is dominated by a mechanism of intramolecular
      cyclization, resulting in intramolecular MAH anhydride formation while preventing
      crosslink formation. The incorporation of highly electron-withdrawing anhydride
      functionality enhances chain scission susceptibility under electron-beam
      irradiation. P(MCA-MAA-MAH) terpolymer thin films can be completely developed at
      dosages as low as 20 microC/cm2 at 50 kV. High-quality positive-tone patterns
      were created with 60 nm feature size achieved in the vapor deposited films.

PMID- 16460109
TI  - Interpolyelectrolyte complexes: a single-molecule insight.
AB  - Polyelectrolyte (PE) complexes (PECs) between long polycation
      poly(methacryloyloxyethyl dimethylbenzylammonium chloride) and short polyanion
      polystyrene sulfonic acid adsorbed onto mica were studied by atomic force
      microscopy. If one component is taken in excess, then a rapid coupling of the
      oppositely charged polyions first leads to the formation of nonequilibrium
      structures when collapsed PEC particles coexist with unreacted PEs molecules. The
      equilibrium PEC particles possess micelle-like core-shell morphology if the short
      polyion is taken in excess. When long PE is given in excess, equilibrium PECs are
      stabilized by wrapping the long polyion around hydrophobic segments of the PEC.
      We propose that transformations of initially formed nonequilibrium aggregates
      proceed through slow reactions (addition or/and substitution) of primary
      complexes with unreacted PEs chains, which finally leads to equilibrium PECs with
      optimized morphology. As expected, the mixing of oppositely charged PEs in a near
      stoichiometric ratio leads to highly aggregated water-insoluble PECs.

PMID- 16460110
TI  - Liquid/liquid interface polymerized porphyrin membranes displaying size-selective
      molecular and ionic permeability.
AB  - Thin polymeric membranes have been formed by liquid/liquid interfacial
      copolymerization of a sterically demanding tetraphenylporphyrin derivative having
      reactive phenol substituents and a second porphyrin having reactive acid chloride
      groups. The out-of-plane steric demand is created by 3,5-hexoxyphenyl groups
      positioned at two of the four meso carbons of the porphyrin ring. The bulky
      substituents were designed to create local pockets and extended pores within the
      resulting ester-linked copolymer. Quantitative measures of molecular and ionic
      transport were obtained by placing membranes over microelectrodes and recording
      voltammetric responses from redox-active probes. The membranes were found to be
      permeable to small molecules and ions, but blocking toward larger ones,
      displaying a sharp size cutoff at a probe diameter of ca. 3.5 A. Molecular
      transport can be modulated by axially ligating pore-blocking moieties to
      available porphyrin metal centers.

PMID- 16460111
TI  - Synthesis of quantum dot-tagged submicrometer polystyrene particles by
      miniemulsion polymerization.
AB  - Submicrometer fluorescent polystyrene (PS) particles have been synthesized via
      miniemulsion polymerization using CdSe/ZnS core-shell quantum dots (QDs). The
      influence of QD concentration, QD coating (either trioctylphosphine oxide (TOPO)
      coated or vinyl-functionalized), and surfactant concentration on the
      polymerization kinetics and the photoluminescence properties of the prepared
      particles has been analyzed. Polymerization kinetics were not altered by the
      presence of QDs, whatever their surface coating. Latexes exhibited particle sizes
      ranging from 100 to 350 nm, depending on surfactant concentration, and a narrow
      particle size distribution was obtained in all cases. The fluorescence signal of
      the particles increased with the number of incorporated TOPO-coated QDs. The
      slight red shift of the emission maximum was correlated with phase separation
      between PS and QDs, which occurred during the polymerization, locating the QDs in
      the vicinity of the particle/water interface. QD-tagged particles displayed
      higher fluorescence intensity with TOPO-coated QDs compared to those with the
      vinyl moiety. The obtained fluorescent particles open up new opportunities for a
      variety of applications in biotechnology.

PMID- 16460112
TI  - Assembly of metal nanoparticle-carbon nanotube composite materials at the
      liquid/liquid interface.
AB  - Carbon nanotubes (CNTs)-mediated self-assembly of metal (Au and Ag) nanoparticles
      at the liquid/liquid interface in the form of a stable nanocomposite film is
      reported. The metallic luster results from the electronic coupling of
      nanoparticles, suggesting the formation of closely packed nanoparticle thin
      films. The interfacial film could be transferred to mica substrates and carbon
      coated transmission electron microscopy (TEM) grids. The transferred films were
      very stable for a prolonged time. The samples were characterized by UV-vis
      spectroscopy, scanning electron microscopy (SEM), TEM, and X-ray photoelectron
      spectroscopy (XPS). SEM and TEM results show that the films formed at the
      liquid/liquid interface are indeed composite materials consisting of CNTs and
      nanoparticles. XPS measurements further indicate the presence of the interaction
      between nanoparticles and CNTs.

PMID- 16460113
TI  - Fluorescent monodisperse silica ellipsoids for optical rotational diffusion
      studies.
AB  - We report on the preparation of monodisperse, fluorescent hematite-silica core
      shell ellipsoids, with adjustable shapes ranging from spindles to nearly spheres,
      that are suitable for optical rotational diffusion studies. Hematite cores are
      grafted with poly(vinylpyrrolidone) which ensures colloidal stability during the
      silica coating provided by the base-catalyzed hydrolysis and polymerization of
      tetraethoxysilane. Using tetramethylammonium hydroxide as base instead of the
      volatile ammonia facilitates continuous seeded growth of silica to colloids with
      a desired aspect ratio. A convenient feature of the hematite-silica particles is
      the rapid dissolution of the iron oxide core by acid, producing hollow silica
      ellipsoids that can be optically matched to near transparency. The control of
      shape and size of the silica ellipsoids, their optical properties, and the fairly
      high yield in comparison to other preparation methods for nonspherical model
      colloids make the ellipsoids very suitable for quantitative studies. As a case in
      point, we have measured the rotational diffusion coefficient of fluorescent
      ellipsoids with rotational fluorescence recovery after photobleaching. Dye
      labeled ellipsoids can be imaged with confocal microscopy.

PMID- 16460114
TI  - Fast microscopic method for large scale determination of structure, morphology,
      and quality of thin colloidal crystals.
AB  - We present a novel fast microscopic method to analyze the crystal structures of
      air-dried or suspended colloidal multilayer systems. Once typical lattice
      spacings of such films are in the range of visible light, characteristic Bragg
      scattering patterns are observed. If in microscopic observations these are
      excluded from image construction, a unique color coding for regions of different
      structures, morphologies, and layer numbers results. Incoherently scattering
      defect structures, however, may not be excluded from image construction and thus
      remain visible with high resolution.

PMID- 16460115
TI  - Synthesis and characterization of uniform alumina-mesoporous silica hybrid
      membranes.
AB  - The synthesis and characterization of alumina-mesoporous silica (alumina-MS)
      hybrid membranes are reported. The hybrids are formed using a variation of the
      evaporative-induced self-assembly (EISA) process reported by Hayward et al.
      (Langmuir 2004, 20, 5998) based on dip coating of an Anopore 200 nm membrane with
      a Brij-56/TEOS/HCl/H2O solution. Numerous analytical methods are used to probe
      both the hybrid material and the silica phase after dissolution of the Anopore
      substrate. Most importantly, He/N2 permeation measurements show that the
      effective pore size of the membrane can be tuned from 20 to 5 nm based on the
      number of dip-coating cycles used. The observed He/N2 permselectivity of 2.7 +/-
      0.11 is nearly identical to the theoretical value obtained (2.65) assuming
      Knudsen diffusion dominates. The selectivity of these membranes is higher than
      that of most commercial "5 nm" membranes (2.29), which is ascribed to the lack of
      pinhole defects in the materials reported here. The hybrid membranes as well as
      the silica obtained after dissolution of the Anopore substrate have been
      characterized using scanning and transmission electron microscopy and X-ray
      diffraction. Those results indicate that the silica deposited in the Anopore
      membrane possesses uniform pores approximately 5 nm in size, consistent with the
      permeation studies. The current work presents an alternative approach to
      materials that possess many of the properties of mesoporous silica thin films
      (i.e., pores of controlled size and topology) without the difficulty of growing
      mesoporous silica thin films on porous supports.

PMID- 16460116
TI  - Nanocrystalline films of Au-Ag, Au-Cu, and Au-Ag-Cu alloys formed at the organic
      aqueous interface.
AB  - By the reaction of the appropriate organometallic precursors and
      tetrakishydroxymethyl phosphonium chloride (THPC) at the toluene-water interface,
      we have prepared nanocrystalline films of Au-Ag and Au-Cu alloys with a range of
      compositions. The films have been characterized by X-ray diffraction, electron
      microscopy, optical spectroscopy, and other techniques, besides compositional
      analysis. The particle size of the nanocrystals in the films varies with the
      composition. The surface plasmon band of the alloy films as well as of the
      organosols obtained by the disintegration of the films by the addition of an
      alkanethiol show the expected composition dependence. It has been possible to
      prepare the nanocrystalline films of a ternary Au-Ag-Cu alloy.

PMID- 16460117
TI  - Quantifying surface coverage of colloidal silica by a cationic peptide using a
      combined centrifugation/time-resolved fluorescence anisotropy approach.
AB  - Recent experimental studies have shown that time-resolved fluorescence anisotropy
      (TRFA) is a promising methodology for in situ characterization of the surface
      modification of aqueous silica nanocolloids. Here we provide a more fundamental
      insight into the principle of this approach and discuss how the adsorption
      parameters for a cationic peptide, Lys-Trp-Lys (denoted using the standard
      shortform KWK), onto Ludox nanoparticles (NPs) are linked to the rotational
      dynamics of rhodamine 6G (R6G) dispersed in the KWK/Ludox mixture. First, the
      adsorption isotherm of KWK on hydrophilic controlled pore glass (CPG-3000) was
      obtained using the traditional centrifugation method, which provides the total
      molar amount of KWK per unit surface area of the silica. Assuming that both CPG
      and Ludox particles possess identical surface properties when suspended in the
      same aqueous buffer, both materials should also have identical adsorption
      properties. Thus, the adsorbed amount of KWK per unit area at a given total KWK
      concentration, as determined by the centrifugation method, can be plotted against
      the fractions of R6G anisotropy decay components at the same KWK concentration to
      relate the anisotropy components to the absolute surface coverage. Using this
      approach, it was determined that the concentration of KWK at which the CPG
      surface was saturated corresponded to the condition g = 0 in the R6G decay, where
      g is the fraction of the nondecaying anisotropy component. This condition means
      that there is no R6G bound to the fraction of Ludox NPs with a radius R > 2.5 nm
      at maximum KWK coverage, consistent with the adsorbed peptide forming a
      continuous layer on the Ludox surface. Hence, the g value obtained from TRFA
      analysis can be used to assess the absolute surface coverage of monolayer
      coatings on colloidal nanoparticles.

PMID- 16460118
TI  - Uniform directional alignment of single-walled carbon nanotubes in viscous
      polymer flow.
AB  - In this work, we probed the effects of shear flow on the alignment of dispersed
      single-walled carbon nanotubes in polymer solutions. Two different systems were
      compared: Single-walled carbon nanotubes dispersed using an anionic surfactant
      and single-walled carbon nanotubes dispersed using an anionic surfactant and a
      weakly binding polymer. It was determined that the addition of the weakly binding
      polymer increased the degree of dispersion of the carbon nanotubes and the
      ability to induce their alignment when subjected to shear forces.

PMID- 16460119
TI  - Kinetics of ultraviolet and plasma surface modification of poly(dimethylsiloxane)
      probed by sum frequency vibrational spectroscopy.
AB  - In numerous applications in microfluidics, cell growth, soft lithography, and
      molecular imprinting, the surface of poly(dimethylsiloxane) (PDMS) is modified
      from a hydrophobic methyl-terminated surface to a hydrophilic hydroxyl-terminated
      surface. In this study, we investigated molecular structural and orientational
      changes at the PDMS-air interface in response to three commonly used surface
      modification processes: exposure to long-wavelength ultraviolet light (UV),
      exposure to short-wavelength UV that generates ozone (UVO), and exposure to
      oxygen plasma (OP). The surfaces of two PDMS compositions (10:1 and 4:1 of base
      polymer/curing agent) were probed during modification, using monolayer-sensitive
      IR + visible sum frequency generation (SFG) vibrational spectroscopy, with two
      different polarization combinations. During PDMS surface modification, the peak
      intensities of CH3 side groups and CH2 cross-link groups decreased, while peak
      intensities of Si-OH groups increased. There was no significant change in the
      average orientation of the CH3 groups on the PDMS surface during modification.
      The concentration of CH3 groups on the surface decreased exponentially with time,
      for all three UV, UVO, and OP modification processes, with first order kinetics
      and time constants of approximately 160, 66, and 0.3 min, respectively. At steady
      state, residual CH3 groups were detected at the PDMS surface for UV and UVO
      treatments; however, there were negligible CH3 groups detected after OP
      modification.

PMID- 16460121
TI  - Nanosized amorphous calcium carbonate stabilized by poly(ethylene oxide)-b
      poly(acrylic acid) block copolymers.
AB  - Particles of amorphous calcium carbonate (ACC), formed in situ from calcium
      chloride by the slow release of carbon dioxide by alkaline hydrolysis of dimethyl
      carbonate in water, are stabilized against coalescence in the presence of very
      small amounts of double hydrophilic block copolymers (DHBCs) composed of
      poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) blocks. Under optimized
      conditions, spherical particles of ACC with diameters less than 100 nm and narrow
      size distribution are obtained at a concentration of only 3 ppm of PEO-b-PAA as
      additive. Equivalent triblock or star DHBCs are compared to diblock copolymers.
      The results are interpreted assuming an interaction of the PAA blocks with the
      surface of the liquid droplets of the concentrated CaCO3 phase, formed by phase
      separation from the initially homogeneous reaction mixture. The adsorption layer
      of the block copolymer protects the liquid precursor of ACC from coalescence
      and/or coagulation.

PMID- 16460120
TI  - Partitioning of organic compounds in phases imitating the headgroup and core
      regions of phospholipid bilayers.
AB  - Solvation free energies of drugs, peptides, and other small molecules in the core
      and headgroup regions of phospholipid bilayers determine their conformations,
      accumulation, and transport properties. The transfer free energy includes the
      energy terms for the formation of a cavity for the solute, the interactions of
      the solute with phospholipids, electrostatic interactions of the solute with the
      membrane, and dipole potentials and entropy terms. The interaction energies with
      phospholipids can be estimated by correlating the partitioning in surrogate
      solvent systems and in the bilayer. As the headgroup surrogate, we use
      diacetylphosphatidylcholine (DAcPC), the acetylated headgroup of the most
      abundant mammalian phospholipid, phosphatidylcholine, which forms a homogeneous
      solution with acceptable viscosity when mixed with water in ratios similar to
      those in the fully hydrated bilayer. The two-phase system of n-hexadecane (C16)
      as the core surrogate and hydrated DAcPC was used to monitor partitioning of 16
      nonionizable compounds. On the bilogarithmic scale, the C16/DAcPC partition
      coefficients correlate neither with those in the C16/water and 1-octanol/water
      systems nor with their difference, which is frequently used as a parameter of
      hydrogen bonding for prediction of the bilayer location of the solutes. The
      C16/DAcPC system provides a satisfactory emulation of the solvation properties of
      the bilayer regions, as reflected in correct predictions of the bilayer location
      for those of the studied chemicals, for which this information is available.

PMID- 16460122
TI  - Hydrogen storage properties of isocyanide-stabilized palladium nanoparticles.
AB  - Monodispersed palladium nanoparticles protected with n-octyl isocyanide were
      prepared, and their hydrogen absorption behavior was evaluated. The formation of
      the nanoparticles has been confirmed by means of 1H NMR and elemental analysis.
      Fourier transform infrared (FT-IR) showed that three distinct bands (2156, 1964,
      and 1611 cm(-1)) assigned to mono-, double-, and triple-bridged isocyanide
      ligands on the palladium surface. The average diameter of the particles was
      estimated to be 2.1 +/- 0.7 nm from observation by transmission electron
      microscopy (TEM). X-ray photoelectron spectroscopy (XPS) analysis revealed that
      the particles contained Pd(0) with little amounts of Pd(II) or Pd(IV), in sharp
      contrast to the thiol- or phosphine-stabilized palladium nanoparticles. The
      absorption and desorption of hydrogen were reversible, and the reactions were
      much faster for the nanoparticles than for the bulk palladium metal, whereas the
      storage capacity was almost the same, 0.6 wt %.

PMID- 16460123
TI  - Optical intensity gradient by colloidal photonic crystals with a graded thickness
      distribution.
AB  - Gradient colloidal crystals with a thickness gradient were prepared by the
      vertical deposition technique with vertically graded concentration suspensions.
      The thickness of the gradient colloidal crystal gradually changes at different
      positions along the specific gradient direction of the crystal. The thickness
      gradient was determined by the concentration gradient, depending on the initial
      colloidal concentration and the settling time. The optical transmission intensity
      at the dip wavelength can be tuned by changing the thickness of the colloidal
      crystals. The gradient colloidal crystals lead to a gradient of optical intensity
      at the dip in transmission light. The gradient of optical intensity at the dip
      increases as the thickness gradient of the colloidal crystal increases.

PMID- 16460124
TI  - Positioning and alignment of lipid tubules on patterned Au substrates.
AB  - This paper presents a method for positioning and aligning self-assembled tubules
      of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphochloline (DC(8,9)PC) by
      withdrawing a patterned Au substrate from tubule solution. The patterned Au
      substrates with alternating bare Au stripes and thiol monolayer stripes are
      formed by microcontact printing. We find that the lipid tubules selectively
      adsorb on the bare Au stripes but show no orientation order. By withdrawing the
      patterned Au substrates at the direction along the stripes from tubule solution,
      the lipid tubules are found to be aligned along the direction of the Au stripes.
      The angular distribution and the density of the aligned lipid tubules depend on
      the withdrawal rates and the adsorption time, respectively. We conclude that
      forces causing tubule alignment that originate in the surface tension associated
      with the moving meniscus dominate alignment forces exerted by the patterned Au
      substrates.

PMID- 16460125
TI  - Double-layer effects and distance dependence of electron transfer in reduction of
      nitro aromatic radical anions.
AB  - The first example of the effect of an electric double layer on the reduction of
      electrochemically generated radical species is reported. The anion radical of
      methyl 5-(2,4-dichlorophenoxy)-2-nitrobenzoate (pesticide bifenox) is
      electrochemically reduced in acetonitrile to a phenylhydroxylamine derivative in
      a process involving three electrons. This heterogeneous reaction is strongly
      influenced by the concentration and nature of the cation of the indifferent
      electrolyte. Depending on the type of tetraalkylammonium cation, the redox
      potential changes by 0.45 V. The kinetic parameters were obtained for five
      tetraalkylammonium hexafluorophosphate salts. The Frumkin correction, which
      assumes that the outer Helmholtz plane coincides with the reaction site, was
      applied to kinetic data of the radical anion reduction. The correction of the
      apparent rate accounted for the observed effect only in the case of
      tetramethylammonium salt. The presence of higher tetraalkylammonium homologues
      causes deviations from the predicted dependence of the electron-transfer rate on
      the phi2 potential of the outer Helmholtz plane. Hence, the nature of the cation
      of the electrolyte exerts a further effect extending beyond the electrostatic
      repulsion only. The corrected rate of electron transfer decreases exponentially
      with increasing size of the alkyl chain of the indifferent electrolyte cation in
      the order methyl > ethyl > propyl > butyl > hexyl. The rate decay is
      characterized by an exponent beta = 0.83. This confirms that the reaction plane
      for the reduction of the bifenox radical anion is different for each electrolyte.
      Due to this fact the Frumkin correction cannot fully account for the observed
      dependence of the heterogeneous rate on the solution composition. The observed
      effect is not specific to the bifenox radical. A similar influence of the
      concentration and nature of the cation of the indifferent electrolyte was
      observed for other nitro compounds, namely, nitrobenzene, nitrobenzoate, and
      nitrofen.

PMID- 16460126
TI  - Physicochemical characterization of variously packed porous plugs of
      hydroxyapatite: streaming potential coupled with conductivity measurements.
AB  - A homemade instrument was used for the measurement of the streaming potential,
      conductivity, and permeability of plugs packed in different densities with
      hydroxyapatite (HAP) particles at 25 degrees C and pH = 7.0 +/- 0.2. KCl
      solutions with ionic strength values in the range of 0.3-300 mM, equilibrated
      with HAP for 3 days, were forced to flow through the plugs. It was found that the
      particle volume fraction of the plug obtained from conductivity measurements was
      slightly higher than that obtained by weighing the solid. This suggested that, in
      addition to the volume of the solid itself, the volume of liquid trapped in the
      cavities of the particles does not contribute to the conductivity of the plug.
      The pH change recorded in the solution passed through the plug was attributed to
      the protonation/deprotonation of the HAP surface groups. Denser packing of the
      HAP crystallites resulted to higher surface conductivities. It was suggested that
      this trend was due to the easier interparticle ion transport in close-packed
      plugs. Considering zeta-potential, the values computed by neglecting surface
      conductivity were significantly underestimated, especially at low ionic strength
      values and at dense packing. More realistic values for the HAP zeta-potential
      were obtained taking into account the surface conductivity. These values were
      practically independent of the material packing during the plug preparation.
      Finally, the total surface conductivity was found to be limited behind the
      slipping plane of the electric double layer developed at the interface of HAP in
      contact with electrolyte solution.

PMID- 16460127
TI  - Electrophoresis of Carreau-drop dispersions with a charge-regulated surface.
AB  - The electrophoresis of a liquid-liquid dispersion, where the dispersed phase
      comprises drops of a shearing-thinning Carreau fluid with a charge-regulated
      surface and the dispersion medium is an aqueous electrolyte solution, is analyzed
      theoretically under the conditions of low surface potential, uniform weak applied
      electric field, and arbitrary double layer thickness. This is the first attempt
      for the description of the electrophoretic behavior of a dispersion containing
      non-Newtonian drops with a charge-regulated surface. We show that, in general,
      the more significant the shear-thinning nature of the drop fluid, the lower the
      concentration of drops, the lower the pH of bulk solution, or the higher the
      concentration of dissociable functional groups on drop surface, the larger the
      mobility. Also, the mobility of a drop may exhibit a local maximum as the
      thickness of the electric double layer surrounding it varies.

PMID- 16460129
TI  - Micropatterned polymer surfaces induced by nonsolvent.
AB  - In this work, we present a facile method for fabricating polymer thin films with
      micropatterned surfaces by evaporating polymer solution containing a small amount
      of nonsolvent of polymer in air. Poly(methyl methacrylate) (PMMA) and polystyrene
      (PS) films with densely packed micropores on the surfaces were fabricated. This
      method was also used to prepare three-dimensional PMMA films with micropatterned
      surfaces. The effects of nonsolvent content; evaporation temperature; and
      interactions between the polymer, solvent, and nonsolvent on the specific
      patterns were investigated, and the formation mechanism of the pores is
      discussed. This simple route can potentially be used, for example, in the large
      scale production of patterned surfaces, three-dimensional painting, and
      hydrophobicity-enhancing coatings.

PMID- 16460128
TI  - Effects of synthetic amphiphilic alpha-helical peptides on the electrochemical
      and structural properties of supported hybrid bilayers on gold.
AB  - Amphiphilic alpha-helices were formed from designed synthetic peptides comprising
      alanine, phenylalanine, and lysine residues. The insertion of the alpha-helical
      peptides into hybrid bilayers assembled on gold was studied by a variety of
      methods to assess the resulting structural characteristics, such as electrical
      resistance and molecular orientation. Self-assembled monolayers (SAMs) of
      dodecanethiol (DDT); octadecanethiol (ODT); and 1,2-dipalmitoyl-sn-glycero-3
      phosphothioethanol (DPPTE) were formed on gold substrates with and without
      incorporated peptide. Supported hybrid bilayers and multilayers of 1,2
      dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were formed on SAMs by the "paint
      freeze" method of bilayer formation. Modeling of electrochemical impedance
      spectroscopy data using equivalent electrochemical circuits revealed that the
      addition of peptide decreased dramatically the resistive element of the bilayer
      films while maintaining the value of the capacitive element, indicating
      successful incorporation of peptide into a well-formed bilayer. Near-edge X-ray
      absorption fine structure spectroscopy data provided evidence that the molecules
      in the SAMs and hybrid multilayers were ordered even in the presence of peptide.
      The peptide insertion into the SAM was confirmed by observing the pi* resonance
      peak correlating with phenylalanine and a peak in the nitrogen K-edge regime
      attributable to the peptide bond.

PMID- 16460130
TI  - Differential labeling of closely spaced biosensor electrodes via electrochemical
      lithography.
AB  - Electrochemical biosensors offer the promise of exceptional scalability and
      parallelizability. To achieve this promise, however, will require the development
      of new methods for the differential labeling of closely spaced electrodes with
      specific biomolecules such as DNA or proteins. Here we report a simple, highly
      selective method for passivating and differentially labeling closely separated
      gold electrodes with oligonucleotides or other biomolecules. Analogous to
      photolithography, where a light-sensitive resist is selectively removed to expose
      specific surfaces to further modification, we passivate gold electrodes with a
      self-assembled alkanethiol monolayer that protects them from modification. The
      monolayer is then electrochemically desorbed at relatively low potentials,
      allowing for the subsequent labeling of the now exposed array element with a
      specific sensing biomolecule. The observed passivation is highly efficient: using
      a C11-OH monolayer as the passivating agent, we do not observe any detectable
      cross-contamination of adjacent electrodes (95 microm separation) upon labeling
      with a stem-loop DNA probe. Critically, the conditions employed are sufficiently
      gentle that depassivation reduces the DNA load on adjacent electrodes by only
      approximately 1%, allowing for the sequential labeling of multiple, closely
      spaced electrodes. This technology paves the way for labeling multiple array
      elements sequentially without observable cross-contamination in a fast and
      controlled manner.

PMID- 16460131
TI  - Highly reproducible method of planar lipid bilayer reconstitution in polymethyl
      methacrylate microfluidic chip.
AB  - We developed a highly reproducible method for planar lipid bilayer reconstitution
      using a microfluidic system made of a polymethyl methacrylate (PMMA) plastic
      substrate. Planar lipid bilayers are formed at apertures, 100 microm in diameter,
      by flowing lipid solution and buffer alternately into an integrated microfluidic
      channel. Since the amount and distribution of the lipid solution at the aperture
      determines the state of the lipid bilayer, controlling them precisely is crucial.
      We designed the geometry of the fluidic system so that a constant amount of lipid
      solution is distributed at the aperture. Then, the layer of lipid solution was
      thinned by applying an external pressure and finally became a bilayer when a
      pressure of 200-400 Pa was applied. The formation process can be simultaneously
      monitored with optical and electrical recordings. The maximum yield for bilayer
      formation was 90%. Using this technique, four lipid bilayers are formed
      simultaneously in a single chip. Finally, a channel current through gramicidin
      peptide ion channels was recorded to prove the compatibility of the chip with
      single molecule electrophysiology.

PMID- 16460132
TI  - Better analysis for better decisions: has pharmacoeconomics come of age?

PMID- 16460133
TI  - Sociodemographic differences in quality of life in rheumatoid arthritis.
AB  - Assessment of health-related quality of life (HR-QOL) in people with rheumatoid
      arthritis (RA) has become important in health research and can inform clinical
      care. Many studies have found sociodemographic differences in the HR-QOL of
      people with RA, and interpreting these differences can be challenging.
      Biological, health disparity, reporting and assessment instrument differences are
      a few of the possible explanations that should be considered when interpreting
      results. Our review of the evidence of sociodemographic differences in HR-QOL in
      people with RA produced 34 articles describing 49 studies.Typically, patients
      with RA who were older, female, less educated, non-employed and/or less affluent
      tended to have significantly lower HR-QOL than other groups. Some evidence also
      indicated that people with RA who are non-White or who live in rural settings may
      also tend to have lower HR-QOL scores, but the number of studies supporting these
      findings was sparse. Researchers and clinicians can optimise their assessment of
      HR-QOL by finding well validated instruments for the context they are working in.
      Additional research is needed to identify the exact causes of HR-QOL differences
      so that quality treatment can be provided to those in need.

PMID- 16460134
TI  - Differential effects of atypical versus typical antipsychotic medication on
      earnings of schizophrenia patients : estimates from a prospective naturalistic
      study.
AB  - BACKGROUND: Rising public and private expenditure on antipsychotic medications is
      concentrated on the cost of second generation or 'atypical' medications, which
      are more expensive than first generation medications and make up a rapidly
      growing share of all antipsychotic prescriptions. Previous studies have examined
      whether the higher acquisition costs of atypicals are offset by other cost and/or
      utilisation benefits. This paper extends this literature by examining possible
      effects of atypicals on earnings and related measures of labour supply in a large
      naturalistic study with a long-term follow-up period. METHODS: We analysed data
      on earnings and other characteristics from the Schizophrenia Care and Assessment
      Program (SCAP), a 3-year longitudinal study (with data collection during the
      years 1997-2003) of 2327 adults with schizophrenia (including schizoaffective and
      schizophreniform disorders) recruited from behavioural healthcare provider
      systems in six areas of the US. We used empirical criteria and data from the SCAP
      database to identify 336 patients aged < 50 years who were in the stable or
      'maintenance' phase of their antipsychotic treatment during the 6 months prior to
      baseline. Effects of atypicals compared with typicals were estimated from Tobit
      regression models that included additional covariates and the baseline-dependent
      variable values. Regression-dependent variables were reported earnings per month,
      hours worked per month, days worked per month and a binary indicator of
      employment. To control for the effect of selection bias in choice of type of
      atypical, we employed an instrumental variables (IV) estimation procedure.
      RESULTS: For all dependent variables, our IV Tobit regressions yielded
      consistently positive coefficient estimates for atypical use that were either
      marginally significant (p < 0.1) or significant (p < 0.05) for earnings,
      significant for hours and days of work and not as consistently significant for
      employment status. Results from these regressions imply a positive effect of
      atypical use on monthly earnings in the range of Dollars US 107-122. In
      regressions that did not control for selection bias by using IVs, coefficients
      for atypical use were often negative and never statistically significant.
      CONCLUSIONS: Our results indicate that higher drug costs of atypicals for
      maintenance-phase treatment are at least partially offset by higher earnings
      among patients. These effects represent benefits to consumers as well as savings
      to taxpayer-supported income transfer programmes. Future studies should seek to
      determine if treatment with atypicals increases patients' earnings via better
      control over negative symptoms and/or improved patient cognition. Both appear to
      be connected with employment and labour supply in patients with schizophrenia,
      and both may be improved through use of atypicals.

PMID- 16460135
TI  - Combination vaccine against invasive meningococcal B and pneumococcal infections:
      potential epidemiological and economic impact in the Netherlands.
AB  - BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis group B are among
      the main causes of invasive bacterial meningitis infections in infants.
      Worldwide, these diseases lead to significant mortality, morbidity and costs. The
      societal impact is especially severe since the majority of cases occur in very
      young infants. A combination vaccine consisting of 9-valent conjugated
      pneumococcal and meningococcal B components is currently being developed. The aim
      of this study was to estimate the potential impact and cost effectiveness from
      the societal perspective of vaccinating infants in The Netherlands with this
      combination pneumococcal and meningococcal B vaccine versus no vaccination.
      METHODS: A Markov cycle model was developed using epidemiological and healthcare
      resource use data from 1996 to 2001. This model was used to project the annual
      costs, benefits and health gains associated with vaccinating all newborns. The
      base year for the costing was 2003 and all costs and health effects were
      discounted at 4%. The results of the analysis are expressed in costs per QALY and
      both probabilistic and univariate sensitivity analyses were used to identify the
      robustness of the results. RESULTS: Annually, an average of 755 cases of invasive
      pneumococcal and meningococcal B infection occurred in infants aged 0-10 years in
      The Netherlands. Introduction of the combination vaccine would prevent 201 cases
      of meningococcal B meningitis and 165 cases of invasive pneumococcal disease per
      year. Additionally, 3410 cases of pneumococcal pneumonia and 46,350 cases of
      otitis media would be prevented. Vaccination would save 35 lives per year and
      prevent 71 cases of severe sequelae. This translates into 860 life-years gained,
      or 1128 QALYs gained. Alongside these health gains, vaccination would prevent
      euro 17,681,370 of direct medical and indirect costs attributable to
      meningococcal and pneumococcal infections in The Netherlands. Depending on
      vaccine price, cost effectiveness varied from euro 3160 (vaccine price per dose
      euro 20) to euro 32,170 (vaccine price euro 60 per dose) per QALY. Base-case cost
      effectiveness (vaccine price euro 40) was euro 17,700 per QALY. The model was
      most sensitive to changes in incidence, vaccine price and duration of protective
      efficacy. CONCLUSION: Our results suggest that the introduction of a combination
      meningococcal B and pneumococcal vaccine into the Dutch infant vaccination
      programme is potentially cost effective compared with no vaccination.

PMID- 16460136
TI  - A multi-country economic evaluation of low-dose aspirin in the primary prevention
      of cardiovascular disease.
AB  - BACKGROUND: Low-dose aspirin (acetylsalicylic acid) is standard care in patients
      with a history of cardiovascular disease (CVD). The use of low-dose aspirin in
      primary prevention is not yet fully established, although meta-analyses and US
      and European guidelines support its use in people at increased risk of CVD. The
      primary objective of this study was to assess the economic consequences of the
      use of low-dose aspirin in the primary prevention of CVD in four European
      countries (UK, Germany, Spain and Italy). METHODS: Based on results (benefits and
      harms) reported in meta-analyses, a state-transition model was developed to
      predict the cost effectiveness of low-dose aspirin in the primary prevention of
      CVD. The model consists of five health states: no history of CVD, history of
      stroke, history of myocardial infarction (MI), history of stroke and MI, and
      death. A 10-year time horizon and 1-year cycles were used. Secondary prevention
      data were derived from the aspirin arm of the CAPRIE (Clopidogrel versus Aspirin
      in Patients at Risk of Ischaemic Events) study. Direct costs from the public
      healthcare payer's perspective were used (euro, 2003 values). Effects were
      expressed in life-years (LY) and QALYs gained. Quality weights were obtained from
      published data.Country-specific discounting was applied on effects and costs
      (3.5% for the UK, 5% for Germany and 3% for Spain and Italy). Univariate
      sensitivity analysis and Monte Carlo simulation were performed to assess
      uncertainty in the results. RESULTS: For patients with an annual risk of coronary
      heart disease (CHD) of 1.5%, the model resulted in 10-year savings with low-dose
      aspirin of on average euro 201 (95% CI 81, 331), euro 281 (95% CI 141, 422), euro
      797 (95% CI 301, 1331) and euro 427 (95% CI 122, 731) per patient in the UK,
      Germany, Spain and Italy, respectively. Average total cost was almost 3- to 4
      fold higher in Spain and Italy than in the UK and Germany. Savings (non
      significant) start in the first year of treatment in all countries. Sensitivity
      analyses on cost of complications, utility, discounting, stroke rate and
      gastrointestinal bleeding rate showed the robustness of the results. From an
      annual risk of CHD of 0.236% for the UK, 0.324% for Germany, 0.244% for Spain and
      0.560% for Italy, low-dose aspirin was cost saving compared with placebo. Monte
      Carlo analysis showed aspirin dominance in about 97% of cases for the three
      studied annual risks of CHD (0.6%, 1.0% and 1.5%) in the UK, Germany and Spain.
      In Italy, aspirin dominance in > 95% of cases was seen at annual risks of 1% and
      1.5%. CONCLUSIONS: Administering low-dose aspirin to patients with an annual risk
      of CHD of > or = 1% appears to be significantly cost saving from the healthcare
      payer's perspective in all countries analysed. Sensitivity analyses (CHD risk and
      bleedings) suggested the results were robust.

PMID- 16460138
TI  - Evaluation of non-medical costs associated with visual impairment in four
      European countries: France, Italy, Germany and the UK.
AB  - INTRODUCTION: Visual impairment is a severe disability that puts a heavy burden
      on individuals, families and society. In developed countries, the two major
      diseases leading to irreversible visual impairment are glaucoma and age-related
      macular degeneration. Their prevalence will increase dramatically with population
      aging. The economic consequences of visual impairment are considerable, but have
      rarely been documented, apart from some 'top-down' estimates based on national
      statistics. We estimated the non-medical costs related to visual impairment in
      four European countries: France, Italy, Germany and the UK. METHODS: Prevalence
      rates of visual impairment, defined according to local regulations, were taken
      from national registers and, for France, from two recent nationwide surveys
      conducted by the French Institute for National Statistics and Economic Studies
      (Institut National de la Statistique et des Etudes Economiques [INSEE]).
      Estimates of the number of non-registered persons were obtained from the
      literature and expert opinion. Estimates of non-medical costs included
      institutional care, non-medical devices, residential adaptations, burden on
      carer, paid home help, loss of income and social allowances related to visual
      impairment. Unit costs (year 2004) were extracted from national databases and
      manufacturers. Healthcare professionals were interviewed to estimate the duration
      of assistance required by visually impaired persons. These durations were used to
      evaluate the cost of paid assistance at home in the four countries. RESULTS: The
      numbers of visually impaired persons were 1.27 million in France, 0.73 million in
      Germany, 1.03 million in Italy and 1.11 million in the UK, including,
      respectively, 56%, 11%, 80% and 72% non-registered persons. The frequency of
      institutionalisation for visually impaired persons were, respectively, 7.8%,
      9.6%, 10.9% and 10%. Total annual costs for visually impaired persons were
      estimated at euro 10,749 million in France, euro 9214 million in Germany, euro
      12,069 million in Italy and euro 15,180 million in the UK. This translated into
      average annual costs per affected individual of euro 8434, euro 12,662, euro
      11,701 and euro 13,674, respectively. The main cost components of visual
      impairment in the community were 'loss of income' (23-43% of community costs),
      'burden on carer' (24-39%) and 'paid assistance' (13-29%). CONCLUSION: Total non
      medical costs associated with visual impairment are considerable. The present
      analysis demonstrates that the preponderant economic consequences of visual
      impairment lie beyond healthcare systems, and that visual impairment has a
      considerable negative impact on productivity. Considering the non-medical social
      dimensions of visual impairment related to the consequent incapacity and
      dependency should encourage payers to finance health innovations that aim to
      preserve vision.

PMID- 16460139
TI  - How much is the cost of visual impairment: caveat emptor.

PMID- 16460137
TI  - The long-term cost effectiveness of treatments for benign prostatic hyperplasia.
AB  - INTRODUCTION: Excellent treatment outcomes with long-term durability and few
      adverse effects are expectations of treatments for chronic conditions. The long
      term cost effectiveness of newer treatments for benign prostatic hyperplasia
      (BPH), including high-energy transurethral microwave thermotherapy (TUMT) and
      combination pharmaceutical therapy, has not been sufficiently studied against
      existing alternatives. The objective of this study was to estimate the
      incremental cost effectiveness of BPH treatment alternatives. METHODS: We
      employed a Markov model over a 20-year time horizon and the payer's perspective
      to evaluate the cost effectiveness of watchful waiting (WW), pharmaceuticals
      (alpha-adrenoceptor antagonists [alpha-blockers], 5-alpha-reductase inhibitors [5
      ARIs], combination therapy), TUMT and transurethral resection of the prostate
      (TURP) in treating BPH. Markov states included improvement in symptoms, no
      improvement in symptoms, adverse effects and death. We used data from the
      published literature for outcomes, including systematic reviews whenever
      possible. Costs were estimated using a managed-care claims database and Medicare
      fee schedules, and were reported in Dollars US, 2004 values. Costs and
      effectiveness outcomes were discounted at a rate of 3% per year. Men (aged > or
      =45 years) with moderate to severe lower urinary tract symptoms and uncomplicated
      BPH were included in the analysis, and results were stratified by age and BPH
      symptom levels. Outcomes included costs, QALYs, incremental cost-utility ratios
      and cost-effectiveness acceptability curves. Sensitivity analysis was performed
      on important parameters, with an emphasis on probabilistic sensitivity analysis.
      RESULTS: alpha-Blockers and TUMT were cost effective for treating moderate
      symptoms using the threshold of Dollars US 50,000 per QALY. For example, at 65
      years of age, the cost per QALY was Dollars US 16,018 for alpha-blockers compared
      with WW and Dollars US 30,204 for TUMT versus alpha-blockers. TURP was the most
      cost-effective treatment for severe symptoms (Dollars US 5824 per QALY ) versus
      WW. Model results were robust to changes in costs and sensitive to the assumed
      probabilities, utility weights, extent of improvement and life expectancy.
      Nevertheless, acceptability curves consistently demonstrated the same
      alternatives as most likely to be cost effective. CONCLUSIONS: Our model suggests
      that alpha-blockers and TURP appear to be the most cost-effective alternatives,
      from a US payer perspective, for BPH patients with moderate and severe symptoms,
      respectively. TUMT was promising for patients with moderate symptoms and the
      oldest patients with severe symptoms, but otherwise was dominated. Value of
      information analysis could be used to determine the net benefit of additional
      research.

PMID- 16460142
TI  - Coaxial carbon nanotubes as shielded nanowires.
AB  - We report transverse polarizabilities of coaxial carbon nanotubes using first
      principles density functional theory. These results demonstrate a shielding of
      the inner nanotube from electric fields by the outer nanotube. This study has
      implications for nanoelectronics, specifically for the possibility of using
      coaxial nanotubes as nanoelectrical wires. Shielding is predicted to be on the
      order of 95% by high-level polarizability calculations. This shielding occurs
      regardless of whether the outer nanotube is metallic or semiconducting. In
      addition, a series of calculations on coaxial nanotubes where the inner nanotube
      is not centered show that the shielding still occurs with approximately the same
      magnitude. These calculations therefore indicate that it would be possible to use
      a coaxial carbon nanotube as a shielded nanowire.

PMID- 16460143
TI  - Relativistic quasidegenerate perturbation theory with four-component general
      multiconfiguration reference functions.
AB  - Relativistic quasidegenerate perturbation theory (QDPT) using general
      multiconfiguration (GMC) reference functions is developed and implemented. It is
      the relativistic counterpart of the nonrelativistic QDPT with GMC reference and
      thus retains all the advantages of the nonrelativistic GMC reference QDPT, such
      as applicability to any configuration space and small computational cost compared
      to the complete configuration-space case. The method is applied to the potential
      energy curves of the ground states of I(2) and Sb(2) molecules, the excitation
      energies of CH(3)I, and the energies of the lowest terms of C, Si, and Ge atoms,
      and is shown to provide a balanced description of potential-energy curves and
      accurate transition energies for systems containing heavy elements and to provide
      much better results compared to the reference function (i.e., active space
      configuration interaction) level.

PMID- 16460144
TI  - Equilibrium thermodynamics from basin-sampling.
AB  - We present a "basin-sampling" approach for calculation of the potential energy
      density of states for classical statistical models. It combines a Wang-Landau
      type uniform sampling of local minima and a novel approach for approximating the
      relative contributions from local minima in terms of the volumes of basins of
      attraction. We have employed basin-sampling to study phase changes in atomic
      clusters modeled by the Lennard-Jones potential and for ionic clusters. The
      approach proves to be efficient for systems involving broken ergodicity and has
      allowed us to calculate converged heat capacity curves for systems that could
      previously only be treated using the harmonic superposition approximation.
      Benchmarks are also provided by comparison with parallel tempering and Wang
      Landau simulations, where these proved feasible.

PMID- 16460145
TI  - The performance of semilocal and hybrid density functionals in 3d transition
      metal chemistry.
AB  - We investigate the performance of contemporary semilocal and hybrid density
      functionals for bond energetics, structures, dipole moments, and harmonic
      frequencies of 3d transition-metal (TM) compounds by comparison with gas-phase
      experiments. Special attention is given to the nonempirical metageneralized
      gradient approximation (meta-GGA) of Tao, Perdew, Staroverov, and Scuseria (TPSS)
      [Phys. Rev. Lett. 91, 146401 (2003)], which has been implemented in TURBOMOLE for
      the present work. Trends and error patterns for classes of homologous compounds
      are analyzed, including dimers, monohydrides, mononitrides, monoxides,
      monofluorides, polyatomic oxides and halogenides, carbonyls, and complexes with
      organic pi ligands such as benzene and cyclopentadienyl. Weakly bound systems
      such as Ca(2), Mn(2), and Zn(2) are discussed. We propose a reference set of
      reaction energies for benchmark purposes. Our all-electron results with quadruple
      zeta valence basis sets validate semilocal density-functional theory as the
      workhorse of computational TM chemistry. Typical errors in bond energies are
      substantially larger than in (organic) main group chemistry, however. The Becke
      Perdew'86 [Phys. Rev. A 38, 3098 (1988); Phys. Rev. B 33, 8822 (1986)] GGA and
      the TPSS meta-GGA have the best price/performance ratio, while the TPSS hybrid
      functional achieves a slightly lower mean absolute error in bond energies. The
      popular Becke three-parameter hybrid B3LYP underbinds significantly and tends to
      overestimate bond distances; we give a possible explanation for this. We further
      show that hybrid mixing does not reduce the width of the error distribution on
      our reference set. The error of a functional for the s-d transfer energy of a TM
      atom does not predict its error for TM bond energies and bond lengths. For
      semilocal functionals, self-interaction error in one- and three-electron bonds
      appears to be a major source of error in TM reaction energies. Nevertheless, TPSS
      predicts the correct ground-state symmetry in the vast majority of cases and
      rarely fails qualitatively. This further confirms TPSS as a general purpose
      functional that works throughout the periodic table. We also give workstation
      timing comparisons for the 645-atom protein crambin.

PMID- 16460146
TI  - The finite state projection algorithm for the solution of the chemical master
      equation.
AB  - This article introduces the finite state projection (FSP) method for use in the
      stochastic analysis of chemically reacting systems. One can describe the chemical
      populations of such systems with probability density vectors that evolve
      according to a set of linear ordinary differential equations known as the
      chemical master equation (CME). Unlike Monte Carlo methods such as the stochastic
      simulation algorithm (SSA) or tau leaping, the FSP directly solves or
      approximates the solution of the CME. If the CME describes a system that has a
      finite number of distinct population vectors, the FSP method provides an exact
      analytical solution. When an infinite or extremely large number of population
      variations is possible, the state space can be truncated, and the FSP method
      provides a certificate of accuracy for how closely the truncated space
      approximation matches the true solution. The proposed FSP algorithm
      systematically increases the projection space in order to meet prespecified
      tolerance in the total probability density error. For any system in which a
      sufficiently accurate FSP exists, the FSP algorithm is shown to converge in a
      finite number of steps. The FSP is utilized to solve two examples taken from the
      field of systems biology, and comparisons are made between the FSP, the SSA, and
      tau leaping algorithms. In both examples, the FSP outperforms the SSA in terms of
      accuracy as well as computational efficiency. Furthermore, due to very small
      molecular counts in these particular examples, the FSP also performs far more
      effectively than tau leaping methods.

PMID- 16460147
TI  - Philicity indices within the spin-polarized density-functional theory framework.
AB  - The electrophilicity index is analyzed within the framework of spin-polarized
      density-functional theory. In this context, constrained philicities, omega(N)
      identical with (mu(N))(2)(2eta(NN)), are introduced in order to define the
      capability of a system to acquire or donate electrons in a process at constant
      spin number. The spin-philicity/spin-donicity indices, omega(S)(+/-) identical
      with (mu(S) (+/-))(2)(2eta(SS)), are examined and rationalized here as the
      philicity of a given system to change its spin-polarization state, as being
      defined through the spin potential mu(S) and spin hardness eta(SS) for a process
      at constant number of electrons. The local extension of these indices has been
      also outlined and numerical results have been discussed on the analysis of the
      electrophilic nature of some simple carbene systems both in the singlet and
      triplet states.

PMID- 16460148
TI  - Nonequilibrium superoperator GW equations.
AB  - Hedin's equations [Phys. Rev. 139, 796 (1965)] for the one-particle equilibrium
      Green's function of a many-electron system are generalized to nonequilibrium open
      systems using two fields that separately control the evolution of the bra and the
      ket of the density matrix. A closed hierarchy is derived for the Green's
      function, the self-energy, the screened potential, the polarization, and the
      vertex function, all expressed as Keldysh matrices in Liouville space.

PMID- 16460149
TI  - The limitations of Slater's element-dependent exchange functional from analytic
      density-functional theory.
AB  - Our recent formulation of the analytic and variational Slater-Roothaan (SR)
      method, which uses Gaussian basis sets to variationally express the molecular
      orbitals, electron density, and the one-body effective potential of density
      functional theory, is reviewed. Variational fitting can be extended to the
      resolution of identity method, where variationality then refers to the error in
      each two-electron integral and not to the total energy. However, a Taylor-series
      analysis shows that all analytic ab initio energies calculated with variational
      fits to two-electron integrals are stationary. It is proposed that the
      appropriate fitting functions be charge neutral and that all ab initio energies
      be evaluated using two-center fits of the two-electron integrals. The SR method
      has its root in Slater's Xalpha method and permits an arbitrary scaling of the
      Slater-Gaspar-Kohn-Sham exchange-correlation potential around each atom in the
      system. The scaling factors are Slater's exchange parameters alpha. Of several
      ways of choosing these parameters, two most obvious are the Hartree-Fock (HF)
      alpha(HF) values and the exact atomic alpha(EA) values. The former are obtained
      by equating the self-consistent Xalpha energy and the HF energies, while the
      latter set reproduces exact atomic energies. In this work, we examine the
      performance of the SR method for predicting atomization energies, bond distances,
      and ionization potentials using the two sets of alpha parameters. The atomization
      energies are calculated for the extended G2 set of 148 molecules for different
      basis-set combinations. The mean error (ME) and mean absolute error (MAE) in
      atomization energies are about 25 and 33 kcal/mol, respectively, for the exact
      atomic alpha(EA) values. The HF values of exchange parameters alpha(HF) give
      somewhat better performance for the atomization energies with ME and MAE being
      about 15 and 26 kcal/mol, respectively. While both sets give performance better
      than the local-density approximation or the HF theory, the errors in atomization
      energy are larger than the target chemical accuracy. To further improve the
      performance of the SR method for atomization energies, a new set of alpha values
      is determined by minimizing the MAE in atomization energies of 148 molecules.
      This new set gives atomization energies half as large (MAE approximately 14.5
      kcal/mol) and that are slightly better than those obtained by one of the most
      widely used generalized-gradient approximations. Further improvements in
      atomization energies require going beyond Slater's functional form for exchange
      employed in this work to allow exchange-correlation interactions between
      electrons of different spins. The MAE in ionization potentials of 49 atoms and
      molecules is about 0.5 eV and that in bond distances of 27 molecules is about
      0.02 A. The overall good performance of the computationally efficient SR method
      using any reasonable set of alpha values makes it a promising method for study of
      large systems.

PMID- 16460150
TI  - Effects of anharmonicity on nonadiabatic electron transfer: a model.
AB  - The effect of anharmonicity in the intramolecular modes of a model system for
      exothermic intramolecular nonadiabatic electron transfer is probed by examining
      the dependence of the transition probability on the exoergicity. The Franck
      Condon factor for the Morse potential is written in terms of the Gauss
      hypergeometric function both for a ground initial state and for the general case,
      and comparisons are made between the first-order perturbation theory results for
      transition probability for harmonic and Morse oscillators. These results are
      verified with quantum dynamical simulations using wave-packet propagations on a
      numerical grid. The transition-probability expression incorporating a high
      frequency quantum mode and low-frequency medium mode is compared for Morse and
      harmonic oscillators in different temperature ranges and with various coarse
      graining treatments of the delta function from the Fermi golden rule expression.
      We find that significant deviations from the harmonic approximation are expected
      for even moderately anharmonic quantum modes at large values of exoergicity. The
      addition of a second quantum mode of opposite displacement negates the anharmonic
      effect at small energy change, but in the inverted regime a significantly flatter
      dependence on exoergicity is predicted for anharmonic modes.

PMID- 16460151
TI  - Efficient step size selection for the tau-leaping simulation method.
AB  - The tau-leaping method of simulating the stochastic time evolution of a well
      stirred chemically reacting system uses a Poisson approximation to take time
      steps that leap over many reaction events. Theory implies that tau leaping should
      be accurate so long as no propensity function changes its value "significantly"
      during any time step tau. Presented here is an improved procedure for estimating
      the largest value for tau that is consistent with this condition. This new tau
      selection procedure is more accurate, easier to code, and faster to execute than
      the currently used procedure. The speedup in execution will be especially
      pronounced in systems that have many reaction channels.

PMID- 16460152
TI  - Grand canonical Markov model: a stochastic theory for open nonequilibrium
      biochemical networks.
AB  - In this paper we present the results of a stochastic model of reversible
      biochemical reaction networks that are being driven through an open boundary,
      such that the system is interacting with its surrounding environment with
      explicit material exchange. The stochastic model is based on the master equation
      approach and is intimately related to the grand canonical ensemble of statistical
      mechanics. We show that it is possible to analytically calculate the joint
      probability function of the random variables describing the number of molecules
      in each state of the system for general linear networks. Definitions of reaction
      chemical potentials and conductances follow from inherent properties of this
      model, providing a description of energy dissipation in the system. We are also
      able to suggest novel methods for experimentally determining reaction fluxes and
      biochemical affinities at nonequilibrium steady state as well as the overall
      network connectivity.

PMID- 16460153
TI  - On the theory underlying the Car-Parrinello method and the role of the fictitious
      mass parameter.
AB  - The theory underlying the Car-Parrinello extended-Lagrangian approach to ab
      initio molecular dynamics (CPMD) is reviewed and reexamined using "heavy" ice as
      a test system. It is emphasized that the adiabatic decoupling in CPMD is not a
      decoupling of electronic orbitals from the ions but only a decoupling of a subset
      of the orbital vibrational modes from the rest of the necessarily coupled system
      of orbitals and ions. Recent work [J. Chem. Phys. 116, 14 (2002)] has pointed out
      that, due to the orbital-ion coupling that remains once adiabatic decoupling has
      been achieved, a large value of the fictitious mass mu can lead to systematic
      errors in the computed forces in CPMD. These errors are further investigated in
      the present work with a focus on those parts of these errors that are not
      corrected simply by rescaling the masses of the ions. It is suggested that any
      comparison of the efficiencies of Born-Oppenheimer molecular dynamics (BOMD) and
      CPMD should be performed at a similar level of accuracy. If accuracy is judged
      according to the average magnitude of the systematic errors in the computed
      forces, the efficiency of BOMD compares more favorably to that of CPMD than
      previous comparisons have suggested.

PMID- 16460154
TI  - Coupled-cluster response theory with linear-r12 corrections: the CC2-R12 model
      for excitation energies.
AB  - Coupled-cluster response theory for vertical excitation energies within the
      second-order approximate coupled-cluster singles-and-doubles model CC2, including
      linear-r(12) corrections, is derived and implemented for Ansatze 1 and 2 of R12
      theory. An orthonormal auxiliary basis set is used for the resolution-of-the
      identity approximation in order to calculate the three- and four-electron
      integrals needed in R12 theory. The basis set convergence is investigated for a
      selected set of atoms and small molecules and it is found that in many cases the
      convergence is not improved. An analysis of the different contributions to
      excitation energies shows that the present scheme for the construction of the R12
      pair functions leads in response theory to an unbalanced description of ground-
      and excited-state wave functions and needs to be generalized to carry the high
      accuracy of R12 methods over to response theory.

PMID- 16460155
TI  - Equilibrium free energies from fast-switching trajectories with large time steps.
AB  - Jarzynski's [Phys. Rev. Lett. 78, 2690 (1997)] identity for the free-energy
      difference between two equilibrium states can be viewed as a special case of a
      more general procedure based on phase-space mappings. Solving a system's equation
      of motion by approximate means generates a mapping that is perfectly valid for
      this purpose, regardless of how closely the solution mimics true time evolution.
      We exploit this fact, using crudely dynamical trajectories to compute free-energy
      differences that are in principle exact. Numerical simulations show that Newton's
      equation can be discretized to low order over very large time steps (limited only
      by the computer's ability to represent resulting values of dynamical variables)
      without sacrificing thermodynamic accuracy. For computing the reversible work
      required to move a particle through a dense liquid, these calculations are more
      efficient than conventional fast-switching simulations by more than an order of
      magnitude. We also explore consequences of the phase-space mapping perspective
      for systems at equilibrium, deriving an exact expression for the statistics of
      energy fluctuations in simulated conservative systems.

PMID- 16460156
TI  - Ab initio study of optical properties of rhodamine 6G molecular dimers.
AB  - Equilibrium atomic geometries of rhodamine 6G (R6G) dye molecule dimers are
      studied using density-functional theory. Electron-energy structure and optical
      properties of R6G H and J dimers are calculated using the generalized gradient
      approximation method with ab initio pseudopotentials. Our theory predicts
      substantial redshifts or blueshifts of the optical absorption spectra of R6G dye
      molecules after aggregation in J or H dimers, respectively. Predicted optical
      properties of R6G dimers are interpreted in terms of interatomic and
      intermolecular interactions. Results of the calculations are discussed in
      comparison with experimental data.

PMID- 16460157
TI  - A classical trajectory study of the photodissociation of T1 acetaldehyde: the
      transition from impulsive to statistical dynamics.
AB  - Previous experimental and theoretical studies of the radical dissociation channel
      of T(1) acetaldehyde show conflicting behavior in the HCO and CH(3) product
      distributions. To resolve these conflicts, a full-dimensional potential-energy
      surface for the dissociation of CH(3)CHO into HCO and CH(3) fragments over the
      barrier on the T(1) surface is developed based on RO-CCSD(T)/cc-pVTZ(DZ) ab
      initio calculations. 20,000 classical trajectories are calculated on this surface
      at each of five initial excess energies, spanning the excitation energies used in
      previous experimental studies, and translational, vibrational, and rotational
      distributions of the radical products are determined. For excess energies near
      the dissociation threshold, both the HCO and CH(3) products are vibrationally
      cold; there is a small amount of HCO rotational excitation and little CH(3)
      rotational excitation, and the reaction energy is partitioned dominantly (>90% at
      threshold) into relative translational motion. Close to threshold the HCO and
      CH(3) rotational distributions are symmetrically shaped, resembling a Gaussian
      function, in agreement with observed experimental HCO rotational distributions.
      As the excess energy increases the calculated HCO and CH(3) rotational
      distributions are observed to change from a Gaussian shape at threshold to one
      more resembling a Boltzmann distribution, a behavior also seen by various
      experimental groups. Thus the distribution of energy in these rotational degrees
      of freedom is observed to change from nonstatistical to apparently statistical,
      as excess energy increases. As the energy above threshold increases all the
      internal and external degrees of freedom are observed to gain population at a
      similar rate, broadly consistent with equipartitioning of the available energy at
      the transition state. These observations generally support the practice of
      separating the reaction dynamics into two reservoirs: an impulsive reservoir, fed
      by the exit channel dynamics, and a statistical reservoir, supported by the
      random distribution of excess energy above the barrier. The HCO rotation,
      however, is favored by approximately a factor of 3 over the statistical
      prediction. Thus, at sufficiently high excess energies, although the HCO
      rotational distribution may be considered statistical, the partitioning of energy
      into HCO rotation is not.

PMID- 16460158
TI  - The small planarization barriers for the amino group in the nucleic acid bases.
AB  - The amino group in the nucleic acid bases frequently interacts with other bases
      or with other molecular systems. Thus any nonplanarity of the amino group may
      affect the molecular recognition of nucleic acids. Ab initio Hartree-Fock (HF)
      and second-order Moller-Plesset perturbation (MP2) levels of theory have been
      used to obtain the equilibrium geometries of the C(l) and C(s) structures for
      five common nucleic acid bases. The energy barriers between the C(l) and C(s)
      structures have also been predicted. A series of correlation consistent basis
      sets up to cc-pCVQZ and aug-cc-pVQZ has been used to systematically study the
      dependence of the amino group nonplanarity. The equilibrium geometries of the
      nucleic acid bases with an amino group, including adenine, guanine, and cytosine,
      are examined carefully. At the MP2 level of theory, larger basis sets decrease
      the extent of nonplanarity of the amino group, but the decrease slows down when
      the QZ basis sets are used, demonstrating the intrinsic property of nonplanarity
      for guanine. For adenine and cytosine the situation is less clear; as the HF
      limit is approached, these two structures become planar. Addition of core
      correlation effects or diffuse functions further decreases the degree of nucleic
      acid base nonplanarity, in comparison to the original cc-pVXZ (X=D, T, and Q)
      basis sets. The aug-cc-pVXZ basis shows smaller degrees of nonplanarity than the
      cc-pCVXZ sets. The aug-cc-pVXZ basis is less size dependent than the cc-pVXZ and
      cc-pCVXZ sets in the prediction of the amino-group-related bond angles and
      dihedral angles and energy barriers for adenine, guanine, and cytosine. The cc
      pCVQZ and aug-cc-pVQZ MP2 results may be regarded as benchmark predictions for
      the five common bases. The predicted classical barriers to planarization are 0.02
      (adenine), 0.74 (guanine), and 0.03(cytosine) kcal mol(-1).

PMID- 16460159
TI  - The frequency-dependent dipole polarizability of the mercury dimer from four
      component relativistic density-functional theory.
AB  - The frequency-dependent dipole polarizability of Hg(2) is calculated using
      response theory within four-component relativistic density-functional theory
      [using the local-density approximation (LDA) and the hybrid functional B3LYP]
      including corrections for the basis-set superposition error. The anisotropic
      component of the polarizability tensor agrees well with the values obtained from
      collision-induced Raman spectroscopy carried out at a wavelength of 488 nm. The
      values obtained from the two density functionals agree closely with the
      experimentally derived anisotropy component of the dipole polarizability, despite
      their rather large differences in the dimer potential-energy curves (LDA is
      strongly overbinding while B3LYP is purely repulsive). The first two refractivity
      virial coefficients for the generalized Clausius-Mossotti function are derived.

PMID- 16460160
TI  - Stretching of hydrogen-bonded OH in the lowest singlet excited electronic state
      of water dimer.
AB  - The lowest singlet excited electronic state of water monomer in the gas phase is
      strictly dissociative along a OH stretch coordinate but changes its nature when
      the stretched OH moiety is hydrogen bonded to a neighboring water molecule. This
      work extends previous exploration of the water dimer excited singlet potential
      energy surface, using computational methods that are reliable even at geometries
      well removed from the ground-state equilibrium. First, the hydrogen-bonded OH
      moiety is stretched far enough to establish the existence of a barrier that is
      sufficient to support a quasibound vibrational state of the OH oscillator near
      the Franck-Condon region. Second, the constraint of an icelike structure is
      relaxed, and it is found that a substantial fraction of liquidlike structures
      also supports a quasibound vibrational state. These potential-energy explorations
      on stretching of the hydrogen-bonded OH moiety in a water dimer are discussed as
      a model for understanding the initial dynamics upon excitation into the lowest
      excited singlet state of condensed water. The possibility is raised that the
      excited-state lifetime may be long enough to allow for exciton migration, which
      would provide a mechanism for energy transport in condensed water phases.

PMID- 16460161
TI  - Control of Li2 wave packet dynamics by modification of the quantum mechanical
      amplitude of a single state.
AB  - Sequences of pulses with different spectra are used to control rotational wave
      packet dynamics in Li(2) by exploiting quantum interference phenomena. Wave
      packet superpositions are excited in a two-step resonant Raman process by two
      different pulses. Interferences between individual states shared by both wave
      packets can be used to enhance or destroy specific components of a superposition
      by varying the time delay between the pulses and/or the relative phase within the
      pulses. Elimination of selected quantum beats is achieved by greater than 94% for
      each case. A simple, yet effective, method for generating different color phase
      locked pairs of laser pulses in a liquid-crystal pulse shaper setup without the
      need for interferometric stabilization schemes is described. The ability to
      manipulate single states of a superposition is an important advancement for
      intuitive control schemes and provides a potential new approach for
      initialization schemes in the field of quantum information.

PMID- 16460162
TI  - Reaction of cyanoacetylene HCCCN(X 1Sigma+) with ground-state carbon atoms C(3P)
      in cold molecular clouds.
AB  - The reaction of the simplest cyanopolyyne, cyanoacetylene [HCCCN(X (1)Sigma(+))],
      with ground-state atomic carbon C((3)P) is investigated theoretically to explore
      the probable routes for the depletion of the famed interstellar molecule HCCCN,
      and the formation of carbon-nitrogen-bearing species in extraterrestrial
      environments particularly of ultralow temperature. Six collision complexes (c1
      c6) without entrance barrier as a result of the carbon atom addition to the pi
      systems of HCCCN are located. The optimized geometries and harmonic frequencies
      of the intermediates, transition states, and products along the isomerization and
      dissociation pathways of each collision complex are obtained by utilizing the
      unrestricted B3YLP6-311G(d,p) level of theory, and the corresponding CCSD(T)/cc
      pVTZ energies are calculated. Subsequently, with the facilitation of Rice
      Ramsperger-Kassel-Marcus (RRKM) and variational RRKM rate constants at collision
      energy of 0-10 kcal/mol, the most probable paths for the titled reaction are
      determined, and the product yields are estimated. Five collision complexes (c1
      c3, c5, and c6) are predicted to give the same products, a chained CCCCN (p2)+H,
      via the linear and most stable intermediate, HCCCCN (i2), while collision complex
      c4 is likely to dissociate back to C+HCCCN. The study suggests that this class of
      reaction is an important route to the destruction of cyanoacetylene and
      cyanopolyynes in general, and to the synthesis of linear carbon-chained nitriles
      at the temperature as low as 10 K to be incorporated in future chemical models of
      interstellar clouds.

PMID- 16460163
TI  - Isotopic replacement in ionic systems: the 4He2+ + 3He-->3He 4He+ + 4He reaction.
AB  - Full quantum dynamics calculations have been carried out for the ionic reaction
      (4)He(2) (+)+(3)He and state-to-state reactive probabilities have been obtained
      using both time-dependent and time-independent approaches. An accurate ab initio
      potential-energy surface has been employed for the present quantum dynamics and
      the two sets of results are shown to be in agreement with each other. The results
      for zero total angular momentum suggest a marked presence of atom exchange
      (isotopic replacement) reaction with probabilities as high as 60%. The reaction
      probabilities are only weakly dependent on the initial vibrational state of the
      reactants, while they are slightly more sensitive to the degree of rotational
      excitation. A brief discussion of the results for selected higher total angular
      momentum values is also presented, while the l-shifting approximation [S. K. Gray
      et al., Phys. Chem. Chem. Phys. 1, 1141 (1999)] has been used to provide
      estimates of the total reaction rates for the title process. Such rates are found
      to be large enough to possibly become experimentally accessible.

PMID- 16460164
TI  - Characterization of the X2A1, A2B1, and X2Pi electronic states of the Ga2H
      molecule and the X2A' and A 2A" isomerization transition states connecting the
      three minima.
AB  - A wide range of highly correlated ab initio methods has been used to predict the
      geometrical parameters of the linear (X (2)Pi) and H-bridged (X (2)A(1) and A
      (2)B(1)) Ga(2)H isomers and two isomerization transition states (X (2)A(') and A
      (2)A(")) connecting the three minima. Dipole moments and vibrational frequencies
      are also obtained. The global minimum X (2)A(1) ground state of the H-bridged
      GaHGa isomer is predicted to lie only 1.6 [1.9 with the zero-point vibrational
      energy (ZPVE) corrections] kcal mol(-1) below the A (2)B(1) state. The X (2)A(1)
      state lies 5.4 kcal mol(-1) below the X (2)Pi ground state of the linear GaGaH
      isomer at the coupled-cluster with single, double, and perturbative triple
      excitations [CCSD(T)] level of theory with the augmented correlation-consistent
      polarized valence quadruple-zeta (aug-cc-pVQZ) basis set. The full triples
      coupled-cluster method is found to alter these CCSD(T) predictions by as much as
      0.3 kcal mol(-1). The forward isomerization barriers from the linear ground state
      to the X (2)A(') and A (2)A(") transition states are determined to be 3.3 and 5.3
      kcal mol(-1), respectively. The reverse isomerization barrier between the X
      (2)A(1) GaHGa structure and the X (2)Pi GaGaH structure is predicted to be 8.6
      (8.2 with the ZPVE corrections) kcal mol(-1) at the aug-cc-pVQZ CCSD(T) level of
      theory.

PMID- 16460165
TI  - Potential-energy surface, van der Waals energy spectrum, and vibronic transitions
      in s-tetrazine-argon complex.
AB  - The van der Waals vibrational states and the structure of the vibronic spectrum
      of s-tetrazine-argon complex have been studied by the ab initio methods. The
      potential-energy surface of the ground S(0) electronic state of the complex has
      been constructed by fitting the analytical many-body expansion to a large set of
      the interaction energy values computed using the second-order Moller-Plesset
      perturbation theory combined with the standard aug-cc-pVDZ basis set. The
      equilibrium structure of the complex found is that with argon located above the
      tetrazine ring at a distance of 3.394 A. The calculated dissociation energy of
      354 cm(-1) is compatible with the experiment. The van der Waals energy spectrum
      calculated from the potential-energy surface is explained analyzing a correlation
      with a simpler energy spectrum of benzene-argon. A new assignment of the S(0)
      S(1) vibronic spectrum is proposed on the basis of the rigorous selection rules,
      vibrational energy levels in S(0) and S(1) states and vibronic transition
      intensities calculated from the electronic transition dipole moment surfaces.

PMID- 16460166
TI  - Ab initio investigations of the radical-radical reaction of O(3P) + C3H3.
AB  - We present ab initio calculations of the reaction of ground-state atomic oxygen
      [O((3)P)] with a propargyl (C(3)H(3)) radical based on the application of the
      density-functional method and the complete basis-set model. It has been predicted
      that the barrierless addition of O((3)P) to C(3)H(3) on the lowest doublet
      potential-energy surface produces several energy-rich intermediates, which
      undergo subsequent isomerization and decomposition steps to generate various
      exothermic reaction products: C(2)H(3)+CO, C(3)H(2)O+H, C(3)H(2)+OH,
      C(2)H(2)+CHO, C(2)H(2)O+CH, C(2)HO+CH(2), and CH(2)O+C(2)H. The respective
      reaction pathways are examined extensively with the aid of statistical Rice
      Ramsperger-Kassel-Marcus calculations, suggesting that the primary reaction
      channel is the formation of propynal (CHCCHO)+H. For the minor C(3)H(2)+OH
      channel, which has been reported in recent gas-phase crossed-beam experiments [H.
      Lee et al., J. Chem. Phys. 119, 9337 (2003); 120, 2215 (2004)], a comparison on
      the basis of prior statistical calculations is made with the nascent rotational
      state distributions of the OH products to elucidate the mechanistic and dynamic
      characteristics at the molecular level.

PMID- 16460167
TI  - Exploring hyperpolarized 83Kr by remotely detected NMR relaxometry.
AB  - For the first time, a hyperpolarized (hp) noble gas with a nuclear electric
      quadrupole moment is available for high-field nuclear-magnetic-resonance (NMR)
      spectroscopy and magnetic-resonance imaging. Hp (83)Kr (I=92) is generated by
      spin-exchange optical pumping and separated from the rubidium vapor used in the
      pumping process. Optical pumping occurs under the previously unstudied condition
      of high krypton gas densities. Signal enhancements of more than three orders of
      magnitude compared to the thermal equilibrium (83)Kr signal at 9.4 T magnetic
      field strength are obtained. The spin-lattice relaxation of (83)Kr is caused
      primarily by quadrupolar couplings during the brief adsorption periods of the
      krypton atoms on the surrounding container walls and significantly limits the
      currently obtained spin polarization. Measurements in macroscopic glass
      containers and in desiccated canine lung tissue at field strengths between 0.05
      and 3 T using remotely detected hp (83)Kr NMR spectroscopy reveal that the
      longitudinal relaxation dramatically accelerates as the magnetic-field strength
      decreases.

PMID- 16460168
TI  - Excited-state dynamics of acetylene excited to individual rotational level of the
      V04K01 subband.
AB  - Dynamics of the IR emission induced by excitation of the acetylene molecule using
      the (3(2)K(a) (0,1,2),A (1)A(u)<--4(1)l(a) (1),X (1)Sigma(g) (+)) transition was
      investigated. The observed IR emission was assigned to transitions between the
      ground-state vibrational levels. Acetylene fluorescence quenching induced by
      external electric and magnetic fields acting upon the system prepared using the
      (3(4)K(a) (1),A (1)A(u)<--0(0)l(a) (0),X (1)Sigma(g) (+)) excitation was also
      studied. External electric field creates an additional radiationless pathway to
      the ground-state levels, coupling levels of the A (1)A(u) excited state to the
      quasiresonant levels of the X (1)Sigma(g) (+) ground state. The level density of
      the ground state in the vicinity of the excited state is very high, thus the
      electric-field-induced transition is irreversible, with the rate constant
      described by the Fermi rule. Magnetic field alters the decay profile without
      changing the fluorescence quantum yield in collisionless conditions. IR emission
      from the CCH transient was detected, and was also affected by the external
      electric and magnetic fields. Acetylene predissociation was demonstrated to
      proceed by the direct S(1)-->S(0) mechanism. The results were explained using the
      previously developed theoretical approach, yielding values of the relevant model
      parameters.

PMID- 16460169
TI  - An extended hindered-rotor model with incorporation of Coriolis and vibrational
      rotational coupling for calculating partition functions and derived quantities.
AB  - Large-amplitude motions, particularly internal rotations, are known to affect
      substantially thermodynamic functions and rate constants of reactions in which
      flexible molecules are involved. Up to now all methods for computing the
      partition functions of these motions rely on the Pitzer approximation of more
      than 50 years ago, in which the large-amplitude motion is treated in complete
      independence of the other (vibrational) degrees of freedom. In this paper an
      extended hindered-rotor model (EHR) is developed in which the vibrational modes,
      treated harmonically, are correctly separated from the large-amplitude motion and
      in which relaxation effects (the changes in the kinetic-energy matrix and
      potential curvature) are taken into account as one moves along the large
      amplitude path. The model also relies on a specific coordinate system in which
      the Coriolis terms vanish at all times in the Hamiltonian. In this way an
      increased level of consistency between the various internal modes is achieved, as
      compared with the more usual hindered-rotor (HR) description. The method is
      illustrated by calculating the entropies and heat capacities on 1,3-butadiene and
      1-butene (with, respectively, one and two internal rotors) and the rate constant
      for the addition reaction of a vinyl radical to ethene. We also discuss various
      variants of the one-dimensional hindered-rotor scheme existing in the literature
      and its relation with the EHR model. It is argued why in most cases the HR
      approach is already quite successful.

PMID- 16460170
TI  - Combined valence bond-molecular mechanics potential-energy surface and direct
      dynamics study of rate constants and kinetic isotope effects for the H + C2H6
      reaction.
AB  - This article presents a multifaceted study of the reaction H+C(2)H(6)-
      >H(2)+C(2)H(5) and three of its deuterium-substituted isotopologs. First we
      present high-level electronic structure calculations by the W1, G3SX, MCG3-MPWB,
      CBS-APNO, and MC-QCISD/3 methods that lead to a best estimate of the barrier
      height of 11.8+/-0.5 kcal/mol. Then we obtain a specific reaction parameter for
      the MPW density functional in order that it reproduces the best estimate of the
      barrier height; this yields the MPW54 functional. The MPW54 functional, as well
      as the MPW60 functional that was previously parametrized for the H+CH(4)
      reaction, is used with canonical variational theory with small-curvature
      tunneling to calculate the rate constants for all four ethane reactions from 200
      to 2000 K. The final MPW54 calculations are based on curvilinear-coordinate
      generalized-normal-mode analysis along the reaction path, and they include scaled
      frequencies and an anharmonic C-C bond torsion. They agree with experiment within
      31% for 467-826 K except for a 38% deviation at 748 K; the results for the
      isotopologs are predictions since these rate constants have never been measured.
      The kinetic isotope effects (KIEs) are analyzed to reveal the contributions from
      subsets of vibrational partition functions and from tunneling, which conspire to
      yield a nonmonotonic temperature dependence for one of the KIEs. The stationary
      points and reaction-path potential of the MPW54 potential-energy surface are then
      used to parametrize a new kind of analytical potential-energy surface that
      combines a semiempirical valence bond formalism for the reactive part of the
      molecule with a standard molecular mechanics force field for the rest; this may
      be considered to be either an extension of molecular mechanics to treat a
      reactive potential-energy surface or a new kind of combined quantum
      mechanical/molecular mechanical (QM/MM) method in which the QM part is
      semiempirical valence bond theory; that is, the new potential-energy surface is a
      combined valence bond molecular mechanics (CVBMM) surface. Rate constants
      calculated with the CVBMM surface agree with the MPW54 rate constants within 12%
      for 534-2000 K and within 23% for 200-491 K. The full CVBMM potential-energy
      surface is now available for use in variety of dynamics calculations, and it
      provides a prototype for developing CVBMM potential-energy surfaces for other
      reactions.

PMID- 16460171
TI  - Interaction potentials and spectroscopy of Hg+.Rg and Cd+.Rg and transport
      coefficients for Hg+ and Cd+ in Rg (Rg=He-Rn).
AB  - High-level ab initio calculations have been performed on the Hg(+).Rg and
      Cd(+).Rg species, where Rg-He-Rn. Potential-energy curves have been calculated
      over a wide range of internuclear separation, sampling the repulsive,
      equilibrium, and long-range regions. From these curves, rovibrational and
      spectroscopic constants were derived and compared to those available from
      previous studies. In addition, transport coefficients were calculated and
      compared to the available experimental data for the cases of Hg(+) in He, Ne, and
      Ar. There are two interesting features relating to the mobility results. One is
      the development of a "mobility minimum" for Hg(+) in the heavier rare gases--with
      weaker minima being found for Cd(+); a "rule of thumb" is presented for
      determining when mobility minima might appear. The second is that excellent
      agreement is found for the direct calculation of mobilities for Hg(+) in (22)Ne,
      and those obtained by scaling the (20)Ne mobilities. The latter result allows us
      to conclude that the mobilities of the various combinations of isotopes can be
      calculated from the results herein via a mass scaling.

PMID- 16460172
TI  - Calculation of the vibronic structure of the X2Pi photoelectron spectra of XCN,
      X=F, Cl, and Br.
AB  - The vibronic structure of the photoelectron spectra of the X (2)Pi state of
      XCN(+) (X=F, Cl, and Br) has been calculated, assuming that the X (2)Pi state can
      be considered as an isolated electronic state. The Renner-Teller coupling of the
      two components of the (2)Pi state via the degenerate bending mode as well as spin
      orbit coupling effects are taken into account. The two stretching modes are
      treated within the so-called linear vibronic-coupling model. The vibronic and
      spin-orbit parameters have been determined by accurate ab initio electronic
      structure calculations. While spin-orbit effects are small in FCN(+), the large
      spin-orbit splitting of the X (2)Pi state of the BrCN(+) leads to a complete
      quenching of the Renner-Teller effect. The X (2)Pi state of the ClCN(+) is shown
      to be of particular interest: here the resonance condition for linear
      relativistic Renner-Teller coupling is approximately fulfilled. This coupling
      mechanism leads to a significant intensity transfer to vibronic levels with odd
      quanta of the bending mode. The calculated spectrum indicates that this novel
      relativistic vibronic-coupling effect should be observable in high-resolution
      (electron energy resolution of the order of a few meV) photoelectron spectra of
      ClCN.

PMID- 16460173
TI  - Kinetic stability of complex molecular clusters.
AB  - This investigation is concerned with modeling the evaporation, or decay, of n
      nonane molecular clusters. We use a unique cluster decay model that was first
      developed to estimate the decay time scale of argon clusters using molecular
      dynamics simulations. In this study we seek to enhance the model so that it
      represents a more complex cluster decay dynamic, suitable for n-nonane clusters.
      Experimental measurements of nucleation rates of n-nonane droplets have been used
      to deduce the rate at which a molecule escapes from the cluster. Typically for an
      n-nonane cluster containing 40 molecules, at an experimental temperature of 225
      K, the empirical decay time, which is the inverse of the decay rate, is estimated
      to be 50 ns. For this time scale, the direct observation of n-nonane cluster
      decay from a molecular-dynamics trajectory is not feasible, since decay events
      are so rare. However, the cluster decay model uses a combination of molecular
      dynamics and stochastic dynamics in order to resolve the problem associated with
      long decay time scales. The model is based on a Langevin treatment that views
      cluster decay as single-particle escape from a confining potential of mean force.
      It is used to predict kinetic decay times of n-nonane clusters. We discover this
      result differs significantly from a classically derived decay time scale
      determined from a continuum thermodynamic treatment of the population balance
      equations of clusters. However, the dynamically generated results obtained from
      the kinetic decay model compare more favorably than the classical results with
      the empirical decay times that are deduced from experimental measurements of n
      nonane clusters.

PMID- 16460174
TI  - One- and two-body densities of carbon isoelectronic series in their low-lying
      multiplet states from explicitly correlated wave functions.
AB  - The (3)P ground state and both the (1)D and (1)S excited states arising from the
      low-lying 1s(2)2s(2)2p(2) configuration of the carbon isoelectronic series are
      studied starting from explicitly correlated multiconfigurational wave functions.
      One- and two-body densities in position space have been calculated and different
      one- and two-body expectation values have been obtained. The effects of
      electronic correlations have been systematically studied. All the calculations
      have been done by means of variational Monte Carlo.

PMID- 16460175
TI  - A small and stable covalently bound trianion.
AB  - Stable doubly charged anions have become well known over the past decade, but the
      knowledge about higher-charged molecules is still sparse. Especially the minimum
      size of a covalently bound trianion which is still stable is an open question.
      Here, we present the smallest trianion of this kind known up to now, namely,
      B(C(2)CO(2))(3) (3-). After establishing its geometrical parameters, we
      investigate its stability with respect to electron autodetachment and
      fragmentation of the molecular framework. Our results lend strong support to the
      notion that this trianion indeed represents a stable compound which should be
      observable in the gas phase.

PMID- 16460176
TI  - Pseudo-Jahn-Teller origin of geometry and pseudorotations in second row tetra
      atomic clusters X4 (X=Na, Mg, Al, Si, P, S).
AB  - Experimentally determined or ab initio calculated molecular geometries carry no
      information about their origin. Employing the Jahn-Teller (JT) vibronic coupling
      effects as the only source of instability and consequent distortions of high
      symmetry molecular configurations, we have worked out a procedure that allows us
      to trace the origin of particular geometries and determine the detailed
      electronic mechanism of their formation. This procedure is illustrated by
      considering a series of X(4) clusters with X=Na, Mg, Al, Si, P, and S. It shows
      explicitly why Na(4), Si(4), and Al(4) have a rhombic geometry in the ground
      state, while Mg(4) and P(4) are tetrahedral, whereas S(4) is a trapezium. Even
      when the minimum-energy geometries are the same (as in the case of rhombic Na(4),
      Si(4), and Al(4)), the electronic mechanism of their formation is quite
      different. In particular, in Na(4) and Si(4) the rhombic minima are produced by a
      strong pseudo JT coupling between two excited states in the square-planar
      configuration (different in the two cases) that stabilizes one of them and makes
      it the ground state by rhombic distortions. The rhombic configuration of Al(4) is
      due to the pseudo JT effect in its ground-state square-planar configuration, and
      the trapezium in S(4) is formed by two pseudo JT couplings essentially involving
      excited states. In several cases this analysis shows also the tunneling paths
      between equivalent configurations.

PMID- 16460177
TI  - Protonated carbonyl sulfide: prospects for the spectroscopic observation of the
      elusive HSCO+ isomer.
AB  - Spurred by the apparent conflict between ab initio predictions and infrared
      spectroscopic evidence regarding the relative stability of isomers of protonated
      carbonyl sulfide, key stationary points on the isomerization surface of HOCS(+)
      have been examined via systematic extrapolations of ab initio energies. Electron
      correlation has been accounted for using second-order Moller-Plesset perturbation
      theory and coupled cluster theory through triple excitations [CCSD, CCSD(T), and
      CCSDT] in conjunction with the correlation consistent hierarchy of basis sets, cc
      pVXZ (X=D,T,Q,5,6). HSCO(+) is predicted to lie lower in energy than HOCS(+) by
      4.86 kcal mol(-1), computed using the focal point extrapolation scheme of Allen
      and co-workers [J. Chem. Phys. 99, 4638 (1993)] with corrections for anharmonic
      zero-point vibrational energy, core correlation, non-Born-Oppenheimer, and scalar
      relativistic effects. A transition state has been located, constituting the
      barrier to isomerization of HSCO(+) to HOCS(+), lying 68.9 kcal mol(-1) higher in
      energy than HSCO(+). This is well above predicted exothermicity [DeltaH(r) (o)(0
      K)=48.1 kcal mol(-1), cc-pVQZ CCSD(T)] for the reaction considered in the
      experiments (HSCO(+)+H(2)-->OCS+H(3) (+)). Though proton tunneling will lead to a
      lower effective barrier, this prediction is consistent with the lack of HSCO(+)
      in electrical discharges in H(2)OCS, since the relative populations of HOCS(+)
      and HSCO(+) will depend on the experimental details of the protonation route
      rather than the relative thermodynamic stability of the isomers. Anharmonic
      vibrational frequencies and vibrationally corrected rotational constants from cc
      pVTZ CCSD(T) cubic and quartic force constants are provided, to aid in the
      spectroscopic observation of the energetically favorable but apparently elusive
      HSCO(+) isomer.

PMID- 16460178
TI  - Accurate ab initio predictions of ionization energies and heats of formation for
      the 2-propyl, phenyl, and benzyl radicals.
AB  - The ionization energies (IEs) for the 2-propyl (2-C(3)H(7)), phenyl (C(6)H(5)),
      and benzyl (C(6)H(5)CH(2)) radicals have been calculated by the wave-function
      based ab initio CCSD(T)/CBS approach, which involves the approximation to the
      complete basis set (CBS) limit at the coupled cluster level with single and
      double excitations plus quasiperturbative triple excitation [CCSD(T)]. The zero
      point vibrational energy correction, the core-valence electronic correction, and
      the scalar relativistic effect correction have been also made in these
      calculations. Although a precise IE value for the 2-C(3)H(7) radical has not been
      directly determined before due to the poor Franck-Condon factor for the
      photoionization transition at the ionization threshold, the experimental value
      deduced indirectly using other known energetic data is found to be in good accord
      with the present CCSD(T)/CBS prediction. The comparison between the predicted
      value through the focal-point analysis and the highly precise experimental value
      for the IE(C(6)H(5)CH(2)) determined in the previous pulsed field ionization
      photoelectron (PFI-PE) study shows that the CCSD(T)/CBS method is capable of
      providing an accurate IE prediction for C(6)H(5)CH(2), achieving an error limit
      of 35 meV. The benchmarking of the CCSD(T)/CBS IE(C(6)H(5)CH(2)) prediction
      suggests that the CCSD(T)/CBS IE(C(6)H(5)) prediction obtained here has a similar
      accuracy of 35 meV. Taking into account this error limit for the CCSD(T)/CBS
      prediction and the experimental uncertainty, the CCSD(T)/CBS IE(C(6)H(5)) value
      is also consistent with the IE(C(6)H(5)) reported in the previous HeI
      photoelectron measurement. Furthermore, the present study provides support for
      the conclusion that the CCSD(T)/CBS approach with high-level energy corrections
      can be used to provide reliable IE predictions for C(3)-C(7) hydrocarbon radicals
      with an uncertainty of +/-35 meV. Employing the atomization scheme, we have also
      computed the 0 K (298 K) heats of formation in kJ/mol at the CCSD(T)/CBS level
      for 2-C(3)H(7)/2-C(3)H(7) (+) ,C(6)H(5)/C(6)H(5) (+), and
      C(6)H(5)CH(2)/C(6)H(5)CH(2) (+) to be 105.2/822.7 (90.0/806.4), 351.4/1148.5
      (340.4/1138.8), and 226.2/929.0 (210.3/912.7), respectively. Comparing these
      values with the available experimental values, we find that the discrepancies for
      the 0 and 298 K heats of formation values are < or =2.6 kJ/mol for 2-C(3)H(7)/2
      C(3)H(7) (+),< or =4.1 kJ/mol for C(6)H(5)/C(6)H(5) (+), and < or =3.2 kJ//mol
      for C(6)H(5)CH(2)C(6)H(5)CH(2) (+).

PMID- 16460179
TI  - Kerr effect as a tool for the investigation of dynamic heterogeneities.
AB  - We propose a dynamic Kerr effect experiment for the distinction between dynamic
      heterogeneous and homogeneous relaxations in glassy systems. The possibility of
      this distinction is due to the inherent nonlinearity of the Kerr effect signal.
      We model the slow reorientational molecular motion in supercooled liquids in
      terms of noninertial rotational diffusion. The Kerr effect response, consisting
      of two terms, is calculated for heterogeneous and for homogeneous variants of the
      stochastic model. It turns out that the experiment is able to distinguish between
      the two scenarios. We furthermore show that exchange between relatively "slow"
      and "fast" environments does not affect the possibility of frequency-selective
      modifications. It is demonstrated how information about changes in the width of
      the relaxation-time distribution can be obtained from experimental results.

PMID- 16460180
TI  - A transferable electrostatic map for solvation effects on amide I vibrations and
      its application to linear and two-dimensional spectroscopy.
AB  - A method for modeling infrared solvent shifts using the electrostatic field
      generated by the solvent is presented. The method is applied to the amide I
      vibration of N-methyl acetamide. Using ab initio calculations the fundamental
      frequency, anharmonicity, and the transition dipoles between the three lowest
      vibrational states are parametrized in terms of the electrostatic field. The
      generated map, which takes into account the electric field and its gradients at
      four molecular positions, is tested in a number of common solvents. Agreement of
      solvent shift and linewidths with experimental Fourier transform infrared (FTIR)
      data is found to within seven and four wave numbers, respectively, for polar
      solvents. This shows that in these solvents electrostatic contributions dominate
      solvation effects and the map is transferable between these types of solvents.
      The effect of motional narrowing arising from the fast solvent fluctuations is
      found to be substantial for the FTIR spectra. Also the two-dimensional infrared
      (2DIR) spectra, simulated using the constructed map, reproduce experimental
      results very well. The effect of anharmonicity fluctuations on the 2DIR spectra
      was found to be negligible.

PMID- 16460181
TI  - Electronic structure study by means of x-ray spectroscopy and theoretical
      calculations of the "ferric star" single molecule magnet.
AB  - The electronic structure of the single molecule magnet system
      {M[Fe(L(1))(2)](3)}4CHCl(3) [M=Fe,Cr;L(1)=CH(3)N(CH(2)CH(2)O)(2) (2-)] has been
      studied using x-ray photoelectron spectroscopy, x-ray-absorption spectroscopy,
      soft-x-ray emission spectroscopy, as well as theoretical density-functional-based
      methods. There is a good agreement between theoretical calculations and
      experimental data. The valence band mainly consists of three bands between 2 and
      30 eV. Both theory and experiments show that the top of the valence band is
      dominated by the hybridization between Fe 3d and O 2p bands. From the shape of
      the Fe 2p spectra it is argued that Fe in the molecule is most likely in the 2+
      charge state. Its neighboring atoms (O,N) exhibit a magnetic polarization
      yielding effective spin S=52 per iron atom, giving a high-spin state molecule
      with a total S=5 effective spin for the case of M=Fe.

PMID- 16460182
TI  - The chemical nature of the (plus sign in circle)C-H...X- (X=Cl or Br) interaction
      in imidazolium halide ionic liquids.
AB  - The C-H...X (X=Cl or Br) interaction is traditionally characterized as a
      relatively weak interaction. However, this interaction becomes very strong in the
      imidazolium-based halide ionic liquids [J. Phys. Chem. 123, 174501 (2005)]. This
      strong interaction had been attributed to the electrostatic interaction between
      the imidazolium cation and the halide anion. In this paper, the chemical nature
      of the (plus sign in circle)C-H...Cl(-) and ( plus sign in circle)C-H...Br(-)
      interactions is investigated by atoms in molecules (AIM) and natural bond orbital
      (NBO) analyses. The AIM calculations indicate that in the EmimX complexes, the
      (plus sign in circle)C-H...Cl(-) and (plus sign in circle)C-H...Br(-)
      interactions have some covalent character, especially the (plus sign in circle)C
      H...Cl(-) interaction. Mulliken, ChelpG charge, and natural bond orbital
      population analyses for these two kinds of interactions indicate that the charge
      transfer is important in the interaction of the cation with the anion. In
      addition, the NBO analysis demonstrated that the stabilization energy is due to
      an n-->sigma(C-H) (*) orbital interaction. However, in the Emim2X and Emim3X
      complexes, the calculated results suggested a dominant electrostatic character
      for the (plus sign in circle)C-H...Cl(-) and (plus sign in circle)C-H...Br(-)
      interactions.

PMID- 16460183
TI  - The effects of solute-solvent electrostatic interactions on solvation dynamics in
      supercritical CO2.
AB  - We present here the results of molecular-dynamics simulation of solvation
      dynamics in supercritical CO(2) at a temperature of about 1.05T(c), where T(c) is
      the critical temperature, and at a series of densities ranging from 0.4 to 2.0 of
      the critical density rho(c). We focus on electrostatic solvation dynamics,
      representing the electronic excitation of the chromophore as a change in its
      charge distribution from a quadrupolar-symmetry ground state to a dipolar excited
      state. Two perturbations are considered, corresponding to different magnitudes of
      solute excited-state dipoles, denoted as d5 and d8. The d8 solute is more
      attractive, leading to a larger enhancement in CO(2) clustering upon solute
      electronic excitation. This has a large impact on solvation dynamics, especially
      at densities below rho(c). At these densities, solvation dynamics is much slower
      for the d8 than for the d5 solute. For both solutes, solvation dynamics becomes
      faster at densities above rho(c) at which solvent clustering diminishes. We show
      that the slowest solvation time scale is associated with solvent clustering and
      we relate it to solute-solvent mutual translational diffusion and the extent of
      change in effective local density resulting from solute electronic excitation.

PMID- 16460184
TI  - Triplet-triplet energy-transfer coupling: theory and calculation.
AB  - Triplet-triplet (TT) energy transfer requires two molecular fragments to exchange
      electrons that carry different spin and energy. In this paper, we analyze and
      report values of the electronic coupling strengths for TT energy transfer. Two
      different methods were proposed and tested: (1) Directly calculating the off
      diagonal Hamiltonian matrix element. This direct coupling scheme was generalized
      from the one used for electron transfer coupling, where two spin-localized
      unrestricted Hartree-Fock wave functions are used as the zero-order reactant and
      product states, and the off-diagonal Hamiltonian matrix elements are calculated
      directly. (2) From energy gaps derived from configuration-interaction-singles
      (CIS) scheme. Both methods yielded very similar results for the systems tested.
      For TT coupling between a pair of face-to-face ethylene molecules, the
      exponential attenuation factor is 2.59 A(-1)(CIS6-311+G(**)), which is about
      twice as large as typical values for electron transfer. With a series of fully
      stacked polyene pairs, we found that the TT coupling magnitudes and attenuation
      rates are very similar irrespective of their molecular size. If the polyenes were
      partially stacked, TT couplings were much reduced, and they decay more rapidly
      with distance than those of full-stacked systems. Our results showed that the TT
      coupling arises mainly from the region of close contact between the donor and
      acceptor frontier orbitals, and the exponential decay of the coupling with
      separation depends on the details of the molecular contacts. With our calculated
      results, nanosecond or picosecond time scales for TT energy-transfer rates are
      possible.

PMID- 16460185
TI  - Inelastic Takahashi hard-rod gas.
AB  - We study a one-dimensional fluid of hard rods interacting with each other via
      binary inelastic collisions and a short-ranged square-well potential. Upon tuning
      the depth and the sign of the well, we investigate the interplay between
      dissipation and cohesive or repulsive forces. Molecular-dynamics simulations of
      the cooling regime indicate that the presence of this simple interparticle
      interaction is sufficient to significantly modify the energy dissipation rates
      expected by Haff's law for the free cooling. The simplicity of the model makes it
      amenable to an analytical approach based on the Boltzmann-Enskog transport
      equation which allows deriving the behavior of the granular temperature.
      Furthermore, in the elastic limit, the model can be solved exactly to provide a
      full thermodynamic description. A meaningful theoretical approximation explaining
      the properties of the inelastic system in interaction with a thermal bath can be
      directly extrapolated from the properties of the corresponding elastic system,
      upon a proper redefinition of the relevant observables. Simulation results both
      in the cooling and driven regimes can be fairly interpreted according to our
      theoretical approach and compare rather well to our predictions.

PMID- 16460186
TI  - n-pentanol at high pressures: rotational isomerism in the liquid phase and the
      liquid-solid phase transition.
AB  - The vibrational spectrum of liquids constituted of chain molecules is difficult
      to analyze because it may have contributions of different rotational isomers. In
      turn, with a proper vibrational assignment, this feature allows us to extract
      information about the effect of temperature or pressure on the molecular
      conformations in the liquid state. In this regard, the information on the
      vibrational spectrum in the solid phase greatly simplifies the vibrational
      analysis of the different rotational conformers existing in the liquid, as the
      molecules usually present all-trans conformations in the crystalline state. Here
      we report room-temperature Raman experiments on n-pentanol performed in a
      sapphire-anvil cell up to 3 GPa. A detailed analysis of the liquid-solid phase
      transition occurring at 1.3 GPa is provided. The analysis of the Raman spectrum
      in the solid phase allows the identification of the bands due to the different
      rotational isomers present in the liquid. The analysis of the spectral region
      corresponding to skeletal vibrations of the carbon chain (800-1200 cm(-1))
      indicates that gauche conformers are promoted by the application of pressure. The
      analysis of the intensity ratio of those bands assigned to trans and gauge
      conformations is used to calculate the change in molecular volume ascribed to the
      trans-gauge isomerization process. We find a value similar to that found in n
      alkanes, i.e., -0.88 cm(3) mol(-1). In addition, we find indication that pressure
      varies the proportions of the different gauge conformers. Thus, it appears that
      the GTTt to TGTt transition in the carbon chain is favored at high pressures. As
      expected, a smaller change in the molecular volume accompanies this conformation
      change.

PMID- 16460187
TI  - Binary nucleation of water and sodium chloride.
AB  - Nucleation processes in the binary water-sodium chloride system are investigated
      in the sense of the classical nucleation theory (CNT). The CNT is modified to be
      able to handle the electrolytic nature of the system and is employed to
      investigate the acceleration of the nucleation process due to the presence of
      sodium chloride in the steam. This phenomenon, frequently observed in the Wilson
      zone of steam turbines, is called early condensation. Therefore, the nucleation
      rates of the water-sodium chloride mixture are of key importance in the power
      cycle industry.

PMID- 16460188
TI  - Quantum-chemical investigation of second-order nonlinear optical chromophores:
      comparison of strong nitrile-based acceptor end groups and role of auxiliary
      donors and acceptors.
AB  - We report a detailed quantum-chemical investigation of donor-acceptor substituted
      dipolar nonlinear optical chromophores incorporating the 4-(dimethylamino)phenyl
      donor end group and a variety of strong heterocyclic acceptor end groups,
      including tricyanofurans and tricyanopyrroles. In particular, we study the
      variation of the molecular second-order polarizability (beta) with the acceptor
      end group and when inserting auxiliary donors (thiophene) and acceptors
      (thiazole) into the pi bridge. Both finite-field calculations (in the context of
      local contributions) and sum-over-states calculations were carried out in order
      to probe the relationship between beta and the chemical structure of the various
      chromophores. The trends obtained with these two methods are fully consistent.
      The large beta values (up to 700 x 10(-30) esu) as well as the observed
      tunability of the optical absorption maximum (lambda(max)) make the chromophores
      investigated here interesting candidates for use in electro-optic applications at
      telecommunications wavelengths.

PMID- 16460189
TI  - Phoretic forces on convex particles from kinetic theory and nonequilibrium
      thermodynamics.
AB  - In this article we derive the phoretic forces acting on a tracer particle, which
      is assumed to be small compared to the mean free path of the surrounding
      nonequilibrium gas, but large compared to the size of the surrounding gas
      molecules. First, we review and extend the calculations of Waldmann [Z.
      Naturforsch. A 14A, 589 (1959)] using half-sphere integrations and an
      accommodation coefficient characterizing the collision process. The presented
      methodology is applied to a gas subject to temperature, pressure, and velocity
      gradients. Corresponding thermophoretic, barophoretic, and rheophoretic forces
      are derived, and explicit expressions for spherical particles are compared to
      known results. Second, nonequilibrium thermodynamics is used to join the
      diffusion equation for the tracer particle with the continuum equations of
      nonisothermal hydrodynamics of the solvent. So doing, the distinct origin of the
      thermophoretic and barophoretic forces is demonstrated. While the latter enters
      similarly to an interaction potential, the former is given by flux-flux
      correlations in terms of a Green-Kubo relation, as shown in detail.

PMID- 16460190
TI  - An equilibrium calculation of the thermal transport coefficients between two
      planes of arbitrary separation in a condensed phase.
AB  - We present a method for the direct calculation at equilibrium of the shear
      viscosity and thermal conductivity over distances as short as one molecular
      diameter. The method is directly applicable to the calculation of viscosity and
      thermal conductivity in inhomogeneities such as the interface between coexisting
      phases. The method makes use of a novel extension of our recently developed
      boundary fluctuation theory.

PMID- 16460191
TI  - Orientation polarization from faster motions in the ultraviscous and glassy
      diethyl phthalate and its entropy.
AB  - Dielectric spectra of the beta relaxation in glassy and ultraviscous liquid
      diethyl phthalate show that its relaxation strength Delta epsilon(beta), the
      distribution of times, and the relaxation rate are more sensitive to temperature
      T in the ultraviscous liquid than in the glassy state. The Delta epsilon(beta)
      against temperature plot has an elbow-shaped break near T(g) of approximately 181
      K, which is remarkably similar to that observed in the entropy, enthalpy, and
      volume against temperature plots, and in the plot of Delta epsilon(beta) against
      the liquid's entropy minus its 0 K value. The ratio of Delta epsilon(beta) to
      diethyl phthalate's entropy, after subtracting the 0 K value, is 1.08 x 10(-3)
      mol K/J in the glassy state at 120.4 K, which decreases slowly to 0.81 x 10(-3)
      mol K/J at 176 K near T(g) and thereafter rapidly increases to 1.57 x 10(-3) mol
      K/J at 190 K. Variation in Delta epsilon(beta) parallels the variation of the
      entropy. A change in the activation energy of the beta process at T>T(g)
      indicates that its rate is also determined by the structure of the ultraviscous
      liquid. Features of beta relaxation are consistent with localized motions of
      molecules and may not involve small-angle motions of all molecules.

PMID- 16460192
TI  - Intermolecular interactions in solid benzene.
AB  - The lattice dynamics and molecular vibrations of benzene and deuterated benzene
      crystals are calculated from force constants derived from density-functional
      theory (DFT) calculations and compared with measured inelastic neutron-scattering
      spectra. A very small change (0.5%) in lattice parameter is required to obtain
      real lattice-mode frequencies across the Brillouin zone. There is a strong
      coupling between wagging and breathing modes away from the zone center. This
      coupling and sensitivity to cell size arises from two basic interactions.
      Firstly, comparatively strong interactions that hold the benzene molecules
      together in layers. These include an intermolecular interaction in which H atoms
      of one molecule link to the center of the aromatic ring of a neighboring
      molecule. The layers are held to each other by weaker interactions, which also
      have components that hold molecules together within a layer. Small changes in the
      lattice parameters change this second type of interaction and account for the
      changes to the lattice dynamics. The calculations also reveal a small auxetic
      effect in that elongation of the crystal along the b axis leads to an increase in
      internal pressure in the ac plane, that is, elongation in the b direction induces
      expansion in the a and c directions.

PMID- 16460193
TI  - Basin hopping simulations for all-atom protein folding.
AB  - We investigate different protocols of the basin hopping technique for de novo
      protein folding. Using the protein free-energy force field PFF01 we report the
      reproducible all-atom folding of the 20-amino-acid tryptophan-cage protein
      [Protein Data Bank (PDB) code: 112y] and of the recently discovered 26-amino-acid
      potassium channel blocker (PDB code: 1wqc), which exhibits an unusual fold. We
      find that simulations with increasing cycle length and random starting
      temperatures perform best in comparison with other parametrizations. The basin
      hopping technique emerges as a simple but very efficient and robust workhorse for
      all-atom protein folding.

PMID- 16460194
TI  - Theoretical analysis of internal fluctuations and bistability in CO oxidation on
      nanoscale surfaces.
AB  - The bistable CO oxidation on a nanoscale surface is characterized by a limited
      number of reacting molecules on the catalytic area. Internal fluctuations due to
      finite-size effects are studied by the master equation with a Langmuir
      Hinshelwood mechanism for CO oxidation. Analytical solutions can be found in a
      reduced one-component model after the adiabatic elimination of one variable which
      in our case is the oxygen coverage. It is shown that near the critical point,
      with decreasing surface area, one cannot distinguish between two macroscopically
      stable stationary states. This is a consequence of the large fluctuations in the
      coverage which occur on a fast time scale. Under these conditions, the transition
      times between the macroscopic states also are no longer separated from the short
      time scale of the coverage fluctuations as is the case for large surface areas
      and far away from the critical point. The corresponding stationary solutions of
      the probability distribution and the mean first passage times calculated in the
      reduced model are supported by numerics of the full two-component model.

PMID- 16460195
TI  - Dispersive-diffusion-controlled distance-dependent recombination in amorphous
      semiconductors.
AB  - The photoluminescence in amorphous semiconductors decays according to the power
      law t(-delta) at long times. The photoluminescence is controlled by dispersive
      transport of electrons. The latter is usually characterized by the power alpha of
      the transient current observed in the time-of-flight experiments. Geminate
      recombination occurs by radiative tunneling which has a distance dependence. In
      this paper, we formulate ways to calculate reaction rates and survival
      probabilities in the case carriers execute dispersive diffusion with long-range
      reactivity. The method is applied to obtain tunneling recombination rates under
      dispersive diffusion. The theoretical condition of observing the relation
      delta=alpha/2+1 is obtained and theoretical recombination rates are compared to
      the kinetics of observed photoluminescence decay in the whole time range
      measured.

PMID- 16460196
TI  - Incidence of partial charges on ion selectivity in potassium channels.
AB  - Potassium channels are membrane proteins known to select potassium over sodium
      ions at a high diffusion rate. We conducted ab initio calculations on a filter
      model of KcsA of about 300 atoms at the Hartree-Fock level of theory. Partial
      charges were derived from the quantum mechanically determined electrostatic
      potential either with Merz-Kollman or Hinsen-Roux schemes. Large polarization
      and/or charge transfer occur on potassium ions located in the filter, while the
      charges on sodium ions remain closer to unity. As a result, a weaker binding is
      obtained for K(+) ions. Using a simplified version of a permeation model based on
      the concerted-motion mechanism for ion translocation within the single-file ion
      channel [P. H. Nelson, J. Chem. Phys. 117, 11396 (2002)], we discuss how
      differences in polarization effects in the adducts with K(+) and Na(+) can play a
      role as for ionic selectivity and conductance.

PMID- 16460197
TI  - Resonant infrared laser-induced desorption of methane condensed on NaCl(100):
      isotope mixture experiments.
AB  - Resonantly enhanced infrared laser-induced desorption of methane condensed on a
      single-crystal NaCl(100) surface is observed after excitation with the widely
      tunable infrared laser output of the free-electron laser at the free-electron
      laser for infrared experiments facility using mass spectroscopic detection and
      time-of-flight analysis. Desorption of methane is observed only when the exciting
      light is in resonance with an internal vibrational mode of the molecule.
      Different intramolecular modes of the three methane isotopologues under study-
      CH(4), CD(4), and CD(3)H--are excited; the degenerate deformation mode nu(4) is
      observed for CH(4) and CD(4) at 7.69 and 10.11 microm, respectively, as well as
      the nu(2) and nu(4) modes of CD(3)H at 7.79, 9.75, and 9.98 microm. The
      desorption signals for the pure layers of these different methane isotopologues
      as well as for different mixtures of two of these are investigated as a function
      of the infrared wavelength and the laser fluence. The desorption behavior for
      pure and mixed layers is compared and the underlying desorption mechanism is
      discussed.

PMID- 16460198
TI  - The importance of hydrogen's potential-energy surface and the strength of the
      forming R-H bond in surface hydrogenation reactions.
AB  - An understanding of surface hydrogenation reactivity is a prevailing issue in
      chemistry and vital to the rational design of future catalysts. In this density
      functional theory study, we address hydrogenation reactivity by examining the
      reaction pathways for N+H-->NH and NH+H-->NH(2) over the close-packed surfaces of
      the 4d transition metals from Zr-Pd. It is found that the minimum-energy reaction
      pathway is dictated by the ease with which H can relocate between hollow-site and
      top-site adsorption geometries. A transition state where H is close to a top site
      reduces the instability associated with bond sharing of metal atoms by H and N
      (NH) (bonding competition). However, if the energy difference between hollow-site
      and top-site adsorption energies (DeltaE(H)) is large this type of transition
      state is unfavorable. Thus we have determined that hydrogenation reactivity is
      primarily controlled by the potential-energy surface of H on the metal, which is
      approximated by DeltaE(H), and that the strength of N (NH) chemisorption energy
      is of less importance. DeltaE(H) has also enabled us to make predictions
      regarding the structure sensitivity of these reactions. Furthermore, we have
      found that the degree of bonding competition at the transition state is
      responsible for the trend in reaction barriers (E(a)) across the transition
      series. When this effect is quantified a very good linear correlation is found
      with E(a). In addition, we find that when considering a particular type of
      reaction pathway, a good linear correlation is found between the destabilizing
      effects of bonding competition at the transition state and the strength of the
      forming N-H (HN-H) bond.

PMID- 16460199
TI  - Theoretical calculations of CH4 and H2 associative desorption from Ni(111): could
      subsurface hydrogen play an important role?
AB  - The results of theoretical calculations of associative desorption of CH(4) and
      H(2) from the Ni(111) surface are presented. Both minimum-energy paths and
      classical dynamics trajectories were generated using density-functional theory to
      estimate the energy and atomic forces. In particular, the recombination of a
      subsurface H atom with adsorbed CH(3) (methyl) or H at the surface was studied.
      The calculations do not show any evidence for enhanced CH(4) formation as the H
      atom emerges from the subsurface site. In fact, there is no minimum-energy path
      for such a concerted process on the energy surface. Dynamical trajectories
      started at the transition state for the H-atom hop from subsurface to surface
      site also did not lead to direct formation of a methane molecule but rather led
      to the formation of a thermally excited H atom and CH(3) group bound to the
      surface. The formation (as well as rupture) of the H-H and C-H bonds only occurs
      on the exposed side of a surface Ni atom. The transition states are quite similar
      for the two molecules, except that in the case of the C-H bond, the underlying Ni
      atom rises out of the surface plane by 0.25 A. Classical dynamics trajectories
      started at the transition state for desorption of CH(4) show that 15% of the
      barrier energy, 0.8 eV, is taken up by Ni atom vibrations, while about 60% goes
      into translation and 20% into vibration of a desorbing CH(4) molecule. The most
      important vibrational modes, accounting for 90% of the vibrational energy, are
      the four high-frequency CH(4) stretches. By time reversibility of the classical
      trajectories, this means that translational energy is most effective for
      dissociative adsorption at low-energy characteristic of thermal excitations but
      energy in stretching modes is also important. Quantum-mechanical tunneling in
      CH(4) dissociative adsorption and associative desorption is estimated to be
      important below 200 K and is, therefore, not expected to play an important role
      under typical conditions. An unexpected mechanism for the rotation of the
      adsorbed methyl group was discovered and illustrated a strong three-center C-H-Ni
      contribution to the methyl-surface bonding.

PMID- 16460200
TI  - Calculation of the crystal-melt interfacial free energy of succinonitrile from
      molecular simulation.
AB  - The crystal-metal interfacial free energy for a six-site model of succinonitrile
      [N triple bond C-(CH(2))(2)-C triple bond N] has been calculated using molecular
      dynamics simulation from the power spectrum of capillary fluctuations in
      interface position. The orientationally averaged magnitude of the interfacial
      free energy is determined to be (7.0+/-0.4)x10(-3) J m(-2). This value is in
      agreement (within the error bars) with the experimental value [(7.9+/-0.8)x10(-3)
      J m(-2)] of Marasli et al. [J. Cryst. Growth 247, 613 (2003)], but is about 20%
      lower than the earlier experimental value [(8.9+/-0.5)x10(-3) J m(-2)] obtained
      by Schaefer et al. [Philos. Mag. 32, 725 (1975)]. In agreement with the
      experiment, the calculated anisotropy of the interfacial free energy of this body
      centered-cubic material is small. In addition, the Turnbull coefficient from our
      simulation is also in agreement with the experiment. This work demonstrates that
      the capillary fluctuation method of Hoyt et al. [Phys. Rev. Lett. 86, 5530
      (2001)] can be successfully applied to determine the crystal-melt interfacial
      free energy of molecular materials.

PMID- 16460201
TI  - Density-functional model cluster studies of EPR g tensors of Fs+ centers on the
      surface of MgO.
AB  - We report g tensors of surface color centers, so-called F(s) (+) centers, of MgO
      calculated with two density-functional approaches using accurately embedded
      cluster models. In line with recent UHV measurements on single-crystalline MgO
      film, we determined only small g-tensor anisotropies and negative shifts Deltag
      identical with g-g(e) for all F(s) (+) sites considered, namely, (001)-terrace,
      step, edge, and corner sites. The g values are very sensitive to the local
      structure of the defect: relaxation reverses the sign of Deltag. However,
      accounting for the spin-orbit interaction either self-consistently or
      perturbatively yields very similar results. In addition to the values of the
      tensor components, their direction with respect to the surface was determined. In
      contrast to edges, significant deviations from ideal C(2v) symmetry were found
      for F(s) (+) centers at steps. Recent data on single-crystalline thin films are
      reevaluated in the light of these results.

PMID- 16460202
TI  - Nonadditivity in van der Waals interactions within multilayers.
AB  - Working at the macroscopic continuum level, we investigate effective van der
      Waals interactions between two layers within a multilayer assembly. By comparing
      the pair interactions between two layers with effective pair interactions within
      an assembly we assess the significant consequences of nonadditivity of van der
      Waals interactions. This allows us to evaluate the best numerical estimate to
      date for the Hamaker coefficient of van der Waals interactions in lipid-water
      multilamellar systems.

PMID- 16460203
TI  - Conditional equilibrium constants in multicomponent heterogeneous adsorption: the
      conditional affinity spectrum.
AB  - The concept of conditional stability constant is extended to the competitive
      binding of small molecules to heterogeneous surfaces or macromolecules via the
      introduction of the conditional affinity spectrum (CAS). The CAS describes the
      distribution of effective binding energies experienced by one complexing agent at
      a fixed concentration of the rest. We show that, when the multicomponent system
      can be described in terms of an underlying affinity spectrum [integral equation
      (IE) approach], the system can always be characterized by means of a CAS. The
      thermodynamic properties of the CAS and its dependence on the concentration of
      the rest of components are discussed. In the context of metal/proton competition,
      analytical expressions for the mean (conditional average affinity) and the
      variance (conditional heterogeneity) of the CAS as functions of pH are reported
      and their physical interpretation discussed. Furthermore, we show that the
      dependence of the CAS variance on pH allows for the analytical determination of
      the correlation coefficient between the binding energies of the metal and the
      proton. Nonideal competitive adsorption isotherm and Frumkin isotherms are used
      to illustrate the results of this work. Finally, the possibility of using CAS
      when the IE approach does not apply (for instance, when multidentate binding is
      present) is explored.

PMID- 16460204
TI  - Structures of bimetallic clusters.
AB  - We report an optimization algorithm for studying bimetallic nanoclusters. The
      algorithm combines two state-of-the-art methods, the genetic algorithm and the
      basin hopping approach, widely employed in the literature for predicting
      structures of pure metallic and nonmetallic clusters. To critically test the
      present algorithm and its use in determining the lowest-energy structures of
      bimetallic nanoclusters, we apply it to study the bimetallic clusters Cu(n)Au(38
      n) (0< or =n< or =38). It is predicted that the Au atoms, being larger in size
      than the Cu atoms, prefer to occupy surface sites showing thus the segregating
      behavior. As the atom fraction of Cu increases, the bimetallic cluster Cu(n)Au(38
      n), as a whole, first takes on an amorphous structure and is followed by dramatic
      changes in structure with the Cu atoms revealing hexagonal, then assuming
      pentagonal, and finally shifting to octahedral symmetry in the Cu-rich range.

PMID- 16460205
TI  - The influence of ultrafast laser pulses on electron transfer in molecular wires
      studied by a non-Markovian density-matrix approach.
AB  - New features of molecular wires can be observed when they are irradiated by laser
      fields. These effects can be achieved by periodically oscillating fields but also
      by short laser pulses. The theoretical foundation used for these investigations
      is a density-matrix formalism where the full system is partitioned into a
      relevant part and a thermal fermionic bath. The derivation of a quantum master
      equation, either based on a time-convolutionless or time-convolution projection
      operator approach, incorporates the interaction with time-dependent laser fields
      nonperturbatively and is valid at low temperatures for weak system-bath coupling.
      From the population dynamics the electrical current through the molecular wire is
      determined. This theory including further extensions is used for the
      determination of electron transport through molecular wires. As examples, we show
      computations of coherent destruction of tunneling in asymmetric periodically
      driven quantum systems, alternating currents and the suppression of the directed
      current by using a short laser pulse.

PMID- 16460206
TI  - Broadband dielectric study of the glass transition in poly(ethyleneglycol)-water
      mixture.
AB  - We performed broadband dielectric measurements of a polyethyleneglycol-water
      mixture in the frequency range between 10 GHz and 1 microHz and the temperature
      range between 300 and 133 K. One relaxation process is observed throughout the
      whole temperature range. The temperature dependence of the relaxation time
      clearly obeys the Vogel-Fulcher law above 183 K, and the Arrhenius law below 183
      K. This observed relaxation process is the secondary process, and the primary
      process related to the glass transition is masked by the low-frequency ionic
      contribution below 183 K. The glass transition concerned with the masked primary
      process leads to the Vogel-Fulcher to Arrhenius transition of the secondary
      process.

PMID- 16460207
TI  - One-dimensional diffusion of colloids in polymer solutions.
AB  - For colloid-polymer systems confined in one-dimensional channels, the diffusion
      of the colloidal particles is obtained by tracking individual particles using
      enhanced video microscopy and digital image analysis. For short times, the
      diffusion is normal, of the Fickian type, with mean-squared displacement varying
      linearly with time. For long times, however, the mean-squared displacement is
      found to increase more slowly with time, being proportional to the square root of
      time, in agreement with the theoretical prediction for diffusion of hard rods in
      one dimension in which mutual crossing of the particles cannot take place. The
      crossover from short-time to long-time diffusion is observed and is found to
      depend on the colloid and polymer concentrations. Unexpectedly, for small polymer
      to-colloid size ratios, it is the polymer rather than the colloid concentration
      which has a leading effect on the colloid diffusion.

PMID- 16460208
TI  - Graphical analysis for gel morphology. III. Gel size and temperature effects on
      the volume phase transition of gels.
AB  - Just after poly(N-isopropylacrylamide) (PNIPA) gels are immersed into hot water
      over the critical temperature, they undergo a two- or three-step shrinking
      accompanied with the whitening. The size of gels and the destination temperature
      were changed and their effects on the shrinking process of PNIPA gels were
      studied. The following important knowledge in the volume phase transition process
      of PNIPA gels was obtained. The first is the fact that the fraction of first
      shrinking is determined by the shrinking rate in the first shrinking stage. The
      second is the fact that PNIPA gels are divided into small parts by the pinning of
      density fluctuation in the final stage of the first shrinking and that the
      shrinking process of each small part undergoes in the secondary shrinking stage.
      The volume phase transition process of PNIPA gels is briefly discussed from the
      viewpoint of the scaling theory.

PMID- 16460209
TI  - Linear polyelectrolytes in tetravalent salt solutions.
AB  - The effect of adding tetravalent salt of different sizes to a solution of linear
      and flexible polyelectrolytes is investigated by molecular dynamics simulations.
      Upon the addition of salt, a chain reexpansion takes place, following a well
      known collapsed conformation. The degrees of collapse and reexpansion increase
      with ion size. In the solution, tetravalent counterions replace monovalent ones
      and condense onto the chains. The condensation for small ions displays a profile
      different from that for large ones. In a high-salt region, ions can form layering
      orders around a polyelectrolyte and locally overcompensate the charge inside.
      Consequently, the integrated charge distribution reveals an oscillatory behavior
      away from a chain. By studying the radial distribution function between monomers
      on different polyelectrolytes, like-charge attraction between chains is
      demonstrated. This attraction is a prerequisite to chain aggregation or
      precipitation. The results show a strong dependence of salt concentration and ion
      size on the properties of polyelectrolyte solutions.

PMID- 16460210
TI  - Temperature-induced crystallization in concentrated suspensions of multiarm star
      polymers: a molecular dynamics study.
AB  - In this work, we study temperature-induced crystallization in dense suspensions
      of multiarm star polymers. This is a continuation of a previous study, which
      identified and studied the emergence of "glassy" amorphous states, in accordance
      with experimental observations. We performed molecular dynamics simulations on
      two types of star polymers: 128-arm stars and 64-arm stars dissolved in n-decane
      in the temperature range of 20-60 degrees C. These supramolecules are modeled as
      "soft spheres" interacting via a theoretically developed potential of mean field.
      Both systems attain a crystalline structure with the characteristics of a face
      centered-cubic (fcc) crystal beyond a certain temperature. Kinetics is sensitive
      on initial configuration. Interestingly, kinetic trapping in "temporary" energy
      wells leads to highly crystalline structures, yet less ordered than their genuine
      equilibrium fcc structure. This complication illustrates the difficulty in
      reaching the equilibrium state, which is crystalline at high temperatures. A
      structural analysis of the final conformations is presented. The effect of size
      dispersity and star functionality of soft spheres on microstructure is also
      examined. Both factors influence crystallization and their effect is quantified
      by our study.

PMID- 16460211
TI  - Three homeotropically aligned nematic liquid crystals: comparison of ultrafast to
      slow time-scale dynamics.
AB  - The dynamics of two nematic liquid crystals, 4-(trans-4(')-n
      octylcyclohexyl)isothiocyanatobenzene and 4-(4-pentyl-cyclohexyl)-benzonitrile,
      are investigated as a function of temperature both in the homeotropically aligned
      nematic phase and in the isotropic phase using optical heterodyne-detected
      optical Kerr effect experiments, which measures the time derivative of the
      polarizability-polarizability-correlation function (orientational relaxation).
      Data are presented over a time range of 500 fs-70 micros for the nematic phase
      and 500 fs to a few hundred nanoseconds for the isotropic phase. The nematic
      dynamics are compared with a previously studied liquid crystal in the nematic
      phase. All three liquid crystals have very similar dynamics in the nematic phase
      that are very different from the isotropic phase. On the slowest time scale (20
      ns-70 micros), a temperature-independent power law, the final power law, t(-f)
      with f approximately 0.5, is observed. On short time scales (approximately 3 ps
      to approximately 1 ns), a temperature-dependent intermediate power law is
      observed with an exponent that displays a linear dependence on the nematic order
      parameter. Between the intermediate power law and the final power law, there is a
      crossover region that has an inflection point. For times that are short compared
      to the intermediate power law (approximately <2 ps), the data decay much faster,
      and can be described as a third power law, although this functional form is not
      definitive. The isotopic phase data have the same features as found in previous
      studies of nematogens in the isotropic phase, i.e., the temperature-independent
      intermediate power law and von Schweidler power law at short to intermediate
      times, and a highly temperature-dependent long time exponential decay that is
      well described by the Landau-de Gennes theory. The results show that liquid
      crystal dynamics in the nematic phase exhibit universal behavior.

PMID- 16460212
TI  - Diffusion of spheres in isotropic and nematic suspensions of rods.
AB  - Diffusion of a small tracer sphere (apoferritin) in isotropic and nematic
      networks [of fd virus] is discussed. For a tracer sphere that is smaller than the
      mesh size of the network, screened hydrodynamic interactions between the sphere
      and the network determine its diffusion coefficient. A theory is developed for
      such interactions as well as their relation to the long-time self-diffusion
      coefficient. Fluorescence correlation spectroscopy measurements on mixtures of
      apoferritin and fd virus are presented. The long-time self-diffusion coefficient
      of apoferritin is measured as a function of the fd-virus concentration, both in
      the isotropic and nematic state, in directions parallel and perpendicular to the
      nematic director. The hydrodynamic screening length of the fd-virus network as a
      function of fd concentration is obtained by combining these experimental data
      with the theory. Surprisingly, the screening length increases with increasing
      concentration in nematic networks. This is due to the increase in the degree of
      alignment, which apparently leads to a strong increase of the screening length.
      Hydrodynamic screening is thus strongly diminished by alignment. A self
      consistent calculation of the screening length does not work at higher
      concentrations, probably due to the strong variation of the typical incident flow
      fields over the contour of a rod.

PMID- 16460213
TI  - Fluctuation effects and monomer-counterion correlations in starlike
      polyelectrolyte systems.
AB  - We performed molecular-dynamics simulation to investigate fluctuation effects of
      monomers and counterions in starlike polyelectrolyte systems. We further study
      correlations between monomers and counterions. These quantities are
      systematically studied by variation of two parameters: the functionality f and
      the degree of dissociation alpha. Fluctuations of monomers and counterions are
      quantified by comparing the corresponding form factors of the monomers and
      counterions with a mean-field approximation. Fluctuations being correlated at
      length scales of the order of the star radius turn out to be negligible with
      increasing arm number f of the stars. At small arm numbers where fluctuation
      effects play a significant role, the use of theoretical mean-field models is
      questionable for a proper description of the monomer- and counterion-form
      factors. Correlations between monomers and counterions are quantified by a cross
      correlation function. At small degree of dissociation alpha this function
      vanishes and indicates weak correlations. Furthermore, we compare our results
      with theoretical mean-field models. We give an appropriate analysis of the
      theoretical form factors and test commonly used counterion density distributions
      with our form factor analysis.

PMID- 16460214
TI  - Theoretical studies of electron transfer through dendrimeric architecture.
AB  - We have analyzed the steady-state electron transfer rate through a bridge of
      dendrimeric architecture. The difference between the linear chain and the
      dendrimeric architecture has also been demonstrated with steady-state rate as a
      main observable in the coherent and incoherent regimes of interactions. It is
      shown that generally the rate of electron transfer in dendrimeric architecture is
      faster than the rate associated with their linear chain counterpart with similar
      kind of bonding connectivities. The rate depends upon the size of the molecule,
      core branching, and the nature of the coupling among the different nodes on the
      dendrimer molecule. Depending upon the nature of the donor and acceptor,
      phenomenological dephasing coefficient due to environment and the geometry of the
      dendrimeric architecture, the modification of electron transfer rate has been
      studied. In the regime of fully coherent interactions where all quantum effects
      are considered the rate shows a multiple inversion due to the dendrimer
      architecture which is neither available in the regime of incoherent interaction
      nor in the linear chain case in similar condition. We have discussed about the
      applicability of our model in metal-molecule-metal junction, photoinduced
      electron transfer process, and molecular conductor.

PMID- 16460215
TI  - Analysis of the shape of dendrimers under shear.
AB  - Nonequilibrium molecular-dynamics simulations are used to investigate the
      molecular shape of dendrimers and linear polymers in a melt and under shear.
      Molecules are modeled at the coarse-grained level using a finitely extensible
      nonlinear elastic bead-spring model. The shape of dendrimers and linear polymers
      at equilibrium and undergoing planar Couette flow is analyzed quantitatively and
      it is related to the shear viscosity. The shape of dendrimers responds
      differently to the influence of shear compared with linear polymers of equivalent
      molecular mass. However, in both cases the transition from Newtonian to non
      Newtonian viscosity behavior corresponds to significant changes in molecular
      symmetry. This suggests that a shape analysis could be used to estimate the onset
      of shear thinning in polymers.

PMID- 16460216
TI  - Brownian dynamics simulations with stiff finitely extensible nonlinear elastic
      Fraenkel springs as approximations to rods in bead-rod models.
AB  - A very stiff finitely extensible nonlinear elastic (FENE)-Fraenkel spring is
      proposed to replace the rigid rod in the bead-rod model. This allows the adoption
      of a fast predictor-corrector method so that large time steps can be taken in
      Brownian dynamics (BD) simulations without over- or understretching the stiff
      springs. In contrast to the simple bead-rod model, BD simulations with beads and
      FENE-Fraenkel (FF) springs yield a random-walk configuration at equilibrium. We
      compare the simulation results of the free-draining bead-FF-spring model with
      those for the bead-rod model in relaxation, start-up of uniaxial extensional, and
      simple shear flows, and find that both methods generate nearly identical results.
      The computational cost per time step for a free-draining BD simulation with the
      proposed bead-FF-spring model is about twice as high as the traditional bead-rod
      model with the midpoint algorithm of Liu [J. Chem. Phys. 90, 5826 (1989)].
      Nevertheless, computations with the bead-FF-spring model are as efficient as
      those with the bead-rod model in extensional flow because the former allows
      larger time steps. Moreover, the Brownian contribution to the stress for the bead
      FF-spring model is isotropic and therefore simplifies the calculation of the
      polymer stresses. In addition, hydrodynamic interaction can more easily be
      incorporated into the bead-FF-spring model than into the bead-rod model since the
      metric force arising from the non-Cartesian coordinates used in bead-rod
      simulations is absent from bead-spring simulations. Finally, with our newly
      developed bead-FF-spring model, existing computer codes for the bead-spring
      models can trivially be converted to ones for effective bead-rod simulations
      merely by replacing the usual FENE or Cohen spring law with a FENE-Fraenkel law,
      and this convertibility provides a very convenient way to perform multiscale BD
      simulations.

PMID- 16460217
TI  - Impaired naming of unique landmarks is associated with left temporal polar
      damage.
AB  - Previous studies have shown that the left temporal polar (TP) region is important
      for the retrieval of proper names for persons. It has been proposed that the key
      specialization of left TP is for proper nouns (rather than names for persons, per
      se), which predicts that left TP should support other categories whose members
      are denoted by proper names (e.g., landmarks). A lesion study tested the
      hypothesis that impaired naming of famous unique landmarks would be associated
      with damage to left TP. A Landmark Recognition and Naming Test was administered
      to participants with lesions to left TP, right TP, or regions outside TP. The
      results provided strong support for the hypothesis: Landmark naming was
      significantly inferior in the left group, supporting the hypothesis. The findings
      converge with previous lesion and functional imaging data to support the idea
      that the left TP region is important for the retrieval of names for unique
      entities. This fits the proposal that left TP contains convergence regions that
      operate as intermediaries between conceptual knowledge retrieval and lexical
      retrieval for classes of unique stimuli (H. Damasio, D. Tranel, T. J. Grabowski,
      R. Adolphs, & A. R. Damasio, 2004).

PMID- 16460218
TI  - Inference of beliefs and emotions in patients with Alzheimer's disease.
AB  - The present study compared 20 patients with mild to moderate Alzheimer's disease
      with 20 older controls (ages 69-94 years) on their ability to make inferences
      about emotions and beliefs in others. Six tasks tested their ability to make 1st
      order and 2nd-order inferences as well as to offer explanations and moral
      evaluations of human action by appeal to emotions and beliefs. Results showed
      that the ability to infer emotions and beliefs in 1st-order tasks remains largely
      intact in patients with mild to moderate Alzheimer's. Patients were able to use
      mental states in the prediction, explanation, and moral evaluation of behavior.
      Impairment on 2nd-order tasks involving inference of mental states was equivalent
      to impairment on control tasks, suggesting that patients' difficulty is secondary
      to their cognitive impairments. ((c) 2006 APA, all rights reserved).

PMID- 16460219
TI  - The profile of memory function in children with autism.
AB  - A clinical memory test was administered to 38 high-functioning children with
      autism and 38 individually matched normal controls, 8-16 years of age. The
      resulting profile of memory abilities in the children with autism was
      characterized by relatively poor memory for complex visual and verbal information
      and spatial working memory with relatively intact associative learning ability,
      verbal working memory, and recognition memory. A stepwise discriminant function
      analysis of the subtests found that the Finger Windows subtest, a measure of
      spatial working memory, discriminated most accurately between the autism and
      normal control groups. A principal components analysis indicated that the factor
      structure of the subtests differed substantially between the children with autism
      and controls, suggesting differing organizations of memory ability.

PMID- 16460220
TI  - Face perception in high-functioning autistic adults: evidence for superior
      processing of face parts, not for a configural face-processing deficit.
AB  - Configural processing in autism was studied in Experiment 1 by using the face
      inversion effect. A normal inversion effect was observed in the participants with
      autism, suggesting intact configural face processing. A priming paradigm using
      partial or complete faces served in Experiment 2 to assess both local and
      configural face processing. Overall, normal priming effects were found in
      participants with autism, irrespective of whether the partial face primes were
      intuitive face parts (i.e., eyes, nose, etc.) or arbitrary segments. An
      exception, however, was that participants with autism showed magnified priming
      with single face parts relative to typically developing control participants. The
      present findings argue for intact configural processing in autism along with an
      enhanced processing for individual face parts. The face-processing peculiarities
      known to characterize autism are discussed on the basis of these results and past
      congruent results with nonsocial stimuli.

PMID- 16460221
TI  - Understanding predictors of functional recovery and outcome 30 months following
      early childhood head injury.
AB  - Much is known about outcome following traumatic brain injury (TBI) in school-age
      children; however, recovery in early childhood is less well understood. Some
      argue that such injuries should lead to good outcome, because of the plasticity
      of the developing brain. Other purport that the young brain is vulnerable, with
      injury likely to result in a substantial impairment (H. G. Taylor & J. Alden,
      1997). The aim of this study was to examine outcomes following TBI during early
      childhood, to plot recovery over the 30 months postinjury, and to identify
      predictors of outcome. The study compared 3 groups of children sustaining mild,
      moderate, and severe TBI, ages 2.0 to 6.11 years at injury, with healthy
      controls. Groups were comparable for preinjury adaptive and behavioral function,
      psychosocial characteristics, age, and gender. Results suggested a strong
      association between injury severity and outcomes across all domains. Further, 30
      month outcome was predicted by injury severity, family factors, and preinjury
      levels of child function. In conclusion, children with more severe injuries and
      lower preinjury adaptive abilities, and whose families are coping poorly, are at
      greatest risk of long-term impairment in day-to-day skills, even several years
      postinjury.

PMID- 16460222
TI  - Tourette's syndrome (TS): cognitive performance in adults with uncomplicated TS.
AB  - Tourette's syndrome (TS) is a neurodevelopmental disorder associated with
      frontostriatal dysfunction. The extent of any cognitive impairment associated
      with uncomplicated TS is unclear, as comorbid psychiatric symptomatology is
      thought to contribute to cognitive deficits. Previous studies have found evidence
      of mild performance deficits, most commonly on tasks that involve inhibitory
      processes. The present study evaluated this in carefully screened adult
      participants with TS. The findings showed the TS group to perform more poorly on
      one test involving behavioral inhibition (sentence completion), but did not
      provide strong support for an interpretation based solely on inhibitory deficits,
      and there was no evidence of impairment on another behavioral inhibition task
      (flanker test). There were also no differences between the groups on tasks
      involving working memory (n-back), task switching, or object alternation
      learning. The findings provide further evidence that uncomplicated TS is
      associated with only mild, circumscribed impairment. The nature of any impairment
      is discussed.

PMID- 16460224
TI  - Effects of two doses of alcohol on simulator driving performance in adults with
      attention-deficit/hyperactivity disorder.
AB  - Prior studies have documented greater impairments in driving performance and
      greater alcohol consumption among adults with attention-deficit/hyperactivity
      disorder (ADHD). This study examined whether alcohol consumption produces a
      differentially greater impairment in driving among adults with ADHD in comparison
      to a community control group. The present study compared 50 adults with ADHD
      (mean age 33 years) and 40 control adults (mean age 29 years) on the effects of 2
      single, acute doses of alcohol (0.04 and 0.08 blood alcohol concentration) and a
      placebo on their driving performance. The authors used a virtual reality driving
      simulator, examiner and self-ratings of simulator performance, and a continuous
      performance test (CPT) to evaluate attention and inhibition. Approximately half
      of the adults in each group were randomized to either the low or high dose
      alcohol treatment arms. Alcohol consumption produced a greater impact on the CPT
      inattention measures of the ADHD than the control group. Similar results were
      obtained for the behavioral observations taken during the operation of the
      driving simulator. Driving simulator scores, however, showed mainly a deleterious
      effect of alcohol on all participants but no differentially greater effect on the
      ADHD group. The present results demonstrated that alcohol may have a greater
      detrimental effect on some aspects of driving performance in ADHD than control
      adults.

PMID- 16460223
TI  - Interhemispheric connectivity and executive functioning in adults with Tourette
      syndrome.
AB  - The prefrontal cortex (PFC) is relatively smaller, and the corpus callosum (CC)
      larger, in adults with Tourette syndrome (TS). The authors explored the possible
      roles of the PFC and the CC in mediating interhemispheric interference and
      coordination in TS adults. They measured performance on M. Kinsbourne and J.
      Cook's (1971) verbal-manual interference task and on the bimanual Purdue Pegboard
      in 38 adults with TS and 34 healthy adults. Compared with controls, TS subjects
      were impaired on the bimanual Purdue Pegboard. On the dual task, right-hand
      performance did not differ between groups, but the normally expected left-hand
      advantage (opposite hemisphere condition) was absent in TS subjects. In the
      control group only, better left-hand performance accompanied larger PFC volumes
      but not CC cross-sectional area. PFC dysfunction might have precluded executive
      control of interference in the TS group.

PMID- 16460225
TI  - Exploring cerebral asymmetries for the verb generation task.
AB  - This study investigated potential right hemisphere involvement in the verb
      generation task. Six divided visual field experiments explored cerebral
      asymmetries for word retrieval in the verb generation task as well as in rhyme
      generation and immediate and delayed word pronunciation. The typical right visual
      field/left hemisphere (RVF/LH) advantage was observed for pronunciation and rhyme
      generation. For verb generation, the RVF/LH advantage was obtained only when
      stimulus items had a single prepotent response and not when there were multiple
      response alternatives. A semantic priming experiment suggested that activation
      for less common, related verbs was maintained for a longer time course within the
      right than within the left hemisphere. The authors suggest that the right
      hemisphere may play a role in continued activation of semantically related
      response alternatives in word generation and discuss methodological implications
      of their findings.

PMID- 16460227
TI  - Gist memory in Alzheimer's disease: evidence from categorized pictures.
AB  - The authors investigated gist memory (the general meaning, idea, or gist conveyed
      by a collection of items) for categorized color photographs in patients with
      Alzheimer's disease (AD) using an experimental paradigm in which participants are
      instructed to respond "yes" when a test item fits with a previously studied
      category, regardless of whether the specific item was actually studied. Compared
      with controls, the patients endorsed fewer studied items and similar numbers of
      nonstudied lure items. After the authors corrected for the baseline false-alarm
      rate, the patients showed a lower level of endorsements for nonstudied lure items
      compared with that of controls, suggesting that their gist memory is impaired.
      Implications of these findings for understanding gist memory and response bias in
      patients with AD are discussed.

PMID- 16460226
TI  - Early patterns of verbal memory impairment in children treated for
      medulloblastoma.
AB  - Children treated for medulloblastoma demonstrate a variety of cognitive deficits
      in addition to white matter and hippocampal neuropathology. This study examined
      40 children treated for medulloblastoma as compared with 40 demographically
      matched controls on the California Verbal Learning Test-Children's Version (D. C.
      Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1994). Results revealed
      significantly poorer performance on indices of word recall in the patient group
      as compared with the controls in addition to milder but still significantly
      poorer recognition memory. These findings suggest that children treated for
      medulloblastoma demonstrate a mixed profile of memory impairment consisting of
      both retrieval and recognition deficits. Implications of these findings for
      understanding neurobehavioral sequelae within pediatric medulloblastoma
      populations and for designing educational and remediation strategies to be used
      with these children are discussed.

PMID- 16460228
TI  - Cognitive estimation impairment in Alzheimer disease and mild cognitive
      impairment.
AB  - Intact executive functioning is believed to be required for performance on tasks
      requiring cognitive estimations. This study used a revised version of a cognitive
      estimations test (CET) to investigate whether patients with Alzheimer's disease
      (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with
      normal elderly controls (NECs). Neuropsychological tests were administered to
      determine the relationship between CET performance and other cognitive domains.
      AD patients displayed impaired CET performance when compared with NECs but MCI
      patients did not. Negative correlations between tests of working memory (WM) and
      semantic memory and the CET were found in NECs and AD patients, indicating that
      these cognitive domains were important for CET performance. Regression analysis
      suggests that AD patients were unable to maintain semantic information in WM to
      perform the task. The authors conclude that AD patients display deficits in
      working memory, semantic memory, and executive function, which are required for
      adequate CET performance.

PMID- 16460229
TI  - New payment model for rural health services in Mongolia.
AB  - This article describes experiences in Mongolia in designing and implementing a
      new method of payment for rural health services. The new method involves using a
      formula that allocates 65% of available funding on the basis of risk-adjusted
      capitation, 20% on the basis of asset costs, 10% on the basis of variations in
      distance-related costs, and 5% on the basis of satisfactory attainment of quality
      of care targets. Rural populations have inferior health services in most
      countries, whether rich or poor. Their situation has deteriorated in most
      transition economies, including Mongolia since 1990. One factor has been the use
      of inappropriate methods of payment of care providers. Changes in payment methods
      have therefore been made in most transition economies with mixed success. One
      factor has been a tendency to over-simplify, for example, to introduce capitation
      without risk adjustment or to make per case payments that ignored casemix. In
      2002, the Mongolian government decided that its crude funding formula for rural
      health services should be replaced. It had two main components. The first was
      payment of an annual grant by the local government from its general revenue on
      the basis of estimated service population, number of inpatient beds, and number
      of clinical staff. The second was an output-based payment per inpatient day from
      the National Health Insurance Fund. The model was administratively complicated,
      and widely believed to be unfair. The two funding agencies were giving
      conflicting types of financial incentives. Most important, the funding methods
      gave few incentives or rewards for service improvement. In some respects, the
      incentives were perverse (such as the encouragement of hospital admission by the
      National Health Insurance Fund). A new funding model was developed through
      statistical analysis of data from routine service reports and opinions
      questionnaires. As noted above, there are components relating to per capita needs
      for care, capital assets, distance, and quality of care. The risk-adjusted
      capitation component determines needs classes by use of age, gender, and family
      income. The model was accepted by all concerned parties, and steps are now being
      taken to implement it under transitional arrangements. Many of the data used to
      parameterize the model are inaccurate and will need to be updated in the near
      future. However, the model is inherently valid, and procedures have been set in
      place that will ensure accuracy is improved on a continuing basis. An important
      reason why the government strongly supported implementation was its commitment to
      implement output-based budgeting across all government sectors. The new model
      provided a convenient way of applying output-based budgeting to one major
      component of the health sector.

PMID- 16460230
TI  - How does cellular senescence prevent cancer?
AB  - It is widely believed that cellular senescence is a tumor suppressor mechanism;
      however, it has not been understood why it is advantageous for organisms to
      retain mutant cells is a postmitotic state rather than simply eliminating them by
      apoptosis. It has recently been proposed that the primary role of cellular
      senescence is in mitotic compartments of fixed size in which spatial
      considerations dictate that a deleted cell is replaced by a neighboring cell. In
      these situations, rather than eliminating the neoplastic clone, deletion of
      mutant cells can paradoxically lead to their increased turnover. If mutant cells
      become senescent, then the compartment is instead progressively filled by
      senescent cells until the mutant clone is eliminated. Since most of the genetic
      alterations responsible for malignancy arise in stem cells, this mechanism may
      have particular relevance to the stem cell niche. In this article the
      implications of this hypothesis are examined in detail and related to
      experimental results. It is further proposed here that blockage of stem cell
      niches by senescent stem cells may account for some of the functional alterations
      observed in stem cell compartments at old age. Clearly, the existence of
      senescent stem cells is central to the proposed hypothesis, and although there is
      preliminary evidence for this assertion it has yet to be proven in vivo. An
      experimental strategy involving double labeling of stem cells with a nucleotide
      label is described that can address this question.

PMID- 16460231
TI  - Differential expression of claudin 1, 3, and 4 during normal mammary gland
      development in the mouse.
AB  - The claudins are a family of tight junction proteins that display varied tissue
      distribution and preferential specificity. We recently identified by microarray
      analysis, members of this family, particularly claudin 1 (cldn1), as highly
      upregulated genes in the mouse mammary gland during early involution. Gene
      expression was confirmed by immunohistochemistry and real-time PCR. We then
      examined gene and protein expression throughout normal mammary gland development.
      The cldn3 gene showed a steady increase in expression from pregnancy to
      involution, while cldn1 and cldn4 gene expression increased during pregnancy, but
      decreased sharply by D10 of lactation, and once again was significantly increased
      by D1 of involution (P < 0.001 for both genes). The different patterns of gene
      expression observed between cldn3, and cldn1, and 4 suggest that different family
      members may be functionally important at different times during mouse mammary
      gland development. All three genes exhibited a high level of expression at day 1
      (D1) of involution, followed by a dramatic decrease in gene expression to day 10
      of involution. Immunostaining with the cldn3 antibody showed intense staining of
      epithelial cells; however, a lesser degree of staining was evident with the cldn1
      antibody. In addition to the lateral staining of epithelial cells, basal staining
      was evident at D1 and D2 of involution and cytoplasmic staining was evident
      during lactation. Since claudins are known to play a role as tight junction
      proteins, lateral and basal staining may suggest a role in other functions such
      as vesicle trafficking or remodeling of tight junctions at different stages of
      mammary gland development. Cldn1 and 3 antibodies also stained epithelial cells
      in mouse mammary tumors. In summary, cldn1, 3, and 4 are differentially expressed
      in the mammary gland during pregnancy, lactation, and involution, suggesting
      different roles for these proteins at different stages of mammary gland function.
      In addition, cldn1 and cldn3 are detected in mammary tumors and the wide
      distribution of cldn3 in particular, suggest specific roles for these proteins in
      mammary tumorigenesis.

PMID- 16460232
TI  - Evaluation of the contraceptive potential of brZPCp vaccine in BALB/c mice: their
      safety and efficacy.
AB  - In this study we have examined the potential ability of Microtus branditi partial
      ZPC (brZPCp) cDNA sequence (436-1150 nt) as a target for immunocontraception.
      Immunogenicity studies and fertility trials were performed in BALB/c mice using
      recombinant construction pCR3.1-brZPC(p). ELISA outcome indicated that antibodies
      could be generated by immunized mice, and IgG titer was increased compared to the
      control. Immunohistochemistry outcome indicated that antibodies could recognize
      native ZP in vivo, which in turn, prevented the binding of sperm to ovulated
      eggs. Antibodies could also recognize recombinant protein expressed by BL21 in
      vitro, which was confirmed by SDS-PAGE and Western blot. Fertility rate was
      reduced by 45% compared to the control immunized with pCR3.1. Meanwhile, there
      was no incidence of significant ovarian pathology in treated mice. This
      experiment indicates that this vaccine can elicit the specific antibody which
      binds exactly to the corresponding ZPC. This construction is proved to be
      immunogenic, and can reduce fertility without obvious oophoritis. The result in
      this study suggests a potentially important method for controlling population for
      its safety and easy production.

PMID- 16460233
TI  - Catechin conjugated with fatty acid inhibits DNA polymerase and angiogenesis.
AB  - Catechins in green tea have anticancer and antiangiogenesis activities, with
      epigallocatechin-3-gallate (EGCG) being the most potent antiangiogenic tea
      catechin. This study examined whether chemical modification of catechin enhanced
      anticancer and antiangiogenic effects. Catechin, conjugated with fatty acid (acyl
      catechin), strongly inhibited DNA polymerase, HL-60 cancer cell growth, and
      angiogenesis. Catechin conjugated with stearic acid [(2R,3S)-3',4',5,7
      tetrahydroxyflavan-3-yl octadecanoate; catechin-C18] was the strongest inhibitor
      in DNA polymerase alpha and beta and angiogenesis assays. Catechin-C18 also
      suppressed human endothelial cell (HUVEC) tube formation on the reconstituted
      basement membrane, suggesting that it affected not only DNA polymerases but also
      signal transduction pathways in HUVECs. These data indicate that acyl-catechins
      target both DNA polymerases and angiogenesis as anticancer agents. These results
      suggest that acylation of catechin is an effective chemical modification to
      improve the anticancer activity of catechin.

PMID- 16460234
TI  - Cloning and functional characterization of the murine caspase-3 gene promoter.
AB  - Several studies have shown that the levels of caspase-3 are upregulated under
      different conditions of apoptosis. Previously, we have shown that activation of T
      cells through the TCR leads to the upregulation of caspase-3 levels. These
      findings highlight the importance of regulating the expression of caspase-3 in
      order to prevent premature cell death. To better understand the regulation of the
      caspase-3 gene, a portion of the 5'- untranslated region was cloned, sequenced,
      and characterized. The segment of the 5'-flanking region of the caspase-3 gene
      was also cloned upstream of a luciferase reporter gene, demonstrating that this
      fragment contains promoter activity. Higher luciferase expression was found with
      several of the promoter deletion constructs in Jurkat T cells but not the mouse
      Neuro-2A neuroblastoma cell line, suggesting the presence of a T-cell-specific
      regulated region. The importance of these sequences is further supported by the
      genomic organization of the human and mouse caspase-3 promoter regions. These
      findings demonstrated that the -2245/+14 region of the caspase-3 promoter shows
      constitutive levels of expression, and that several regions of the promoter play
      a role in basal regulation. Finally, some of the conserved transcription factor
      binding sites identified between the human and mouse promoters appear to play an
      important role in lymphoid cells.

PMID- 16460236
TI  - High levels of oxidative stress globally inhibit gene transcription and histone
      acetylation.
AB  - Oxidative stress has been shown to induce ubiquitynation of RNA polymerase II,
      but direct bearing of that phenomenon on global transcription still remains
      elusive. In this report, we show that high levels of cellular oxidative stress
      globally inhibit gene transcription, and that this decrease in transcription is
      only partly attributable to reduced binding of RNA polymerase II to a model gene
      promoter. Importantly, we show that this decrease in transcription correlates
      with a significant decrease in histone H3 and H4 acetylation levels both
      throughout a model gene, and also globally in the nucleus of cells. Our results
      suggest that high levels of oxidative stress can inhibit transcription by a
      mechanism, at least in part, that impedes global histone acetylation levels.

PMID- 16460235
TI  - Interaction of antioxidant flavonoids with tRNA: intercalation or external
      binding and comparison with flavonoid-DNA adducts.
AB  - Antioxidants are essential to good health. Flavonoids are powerful antioxidants,
      and prevent DNA damage. The antioxidative protections are related to their
      binding modes to a DNA duplex and complexation with free radicals in vivo.
      Recently we reported the interaction of flavonoids with DNA in vitro (Kanakis et
      al., J. Biomol. Struct. Dyn. 22, 719-724, 2005), where polyphenol different
      binding modes were discussed. The aim of this study was to examine the
      interaction of transfer RNA with quercetin (que), kaempferol (kae), and
      delphinidin (del) in aqueous solution at physiological conditions and to make a
      comparison with the corresponding pigment-DNA adducts. Constant tRNA
      concentration (6.25 mM) and various drug/RNA(phosphate) molar ratios of 1/48 to
      1/8 were used. FTIR and UV-visible difference spectroscopic methods have been
      applied to determine the drug binding mode, the binding constants, and the
      effects of drug complexation on the stability and conformation of tRNA duplex.
      Both intercalative and external binding modes were observed. Structural analysis
      showed que, kae, and a del intercalate tRNA duplex with minor external binding to
      the major or minor groove and the backbone phosphate group with overall binding
      constants K (que) = 4.80 x 10(4) M(1), K (kae) = 4.65 x 10(4) M(1), and K (del) =
      9.47 x 10(4) M(1). The stability of adduct formation is in the order of del > que
      > kae. A comparison with flavonoids-DNA adducts showed both intercalation and
      external bindings with the stability order K (que) = 7.25 x 10(4) M(1), K (kae) =
      3.60 x 10(4) M(1), and K (del) = 1.66 x 10(4) M(1). Low flavonoid concentration
      induces helical stabilization, whereas high pigment content causes helix opening.
      A partial Bto A-DNA transition occurs at high drug concentration, while tRNA
      remains in the A-family structure.

PMID- 16460237
TI  - FDA report.

PMID- 16460238
TI  - Peri-implant bone organization under immediate loading state. Circularly
      polarized light analyses: a minipig study.
AB  - BACKGROUND: Immediate loading of dental implants is currently one of the most
      examined topics in implant dentistry. Using screw implants with a microstructured
      surface and bone-quality-adapted insertion procedures, osseointegration is
      achieved when implants are initially stable and when splinted with the
      superstructure. Despite reported success, there is a shortage of information
      relating to remodeling and peri-implant bone formation with immediately loaded
      implants. METHODS: Four to six immediately loaded and unloaded dental implants
      with a microstructured surface were placed in the mandible and the maxilla in
      seven minipigs. A total of 85 implants were placed. After a 4-month healing
      period, all implants were retrieved. Histomorphometry was performed using a light
      microscope in transmitted polarized light connected to a high-resolution video
      camera interfaced to a monitor and personal computer. This optical system was
      associated with a digitizing pad and a histomorphometry software package with
      image capturing capabilities. RESULTS: Implants showed osseointegration if the
      average insertion torque of the implants within one bridge was >35 Ncm. If the
      primary stability of the bridge was <35 Ncm, all implants in the quadrant were
      lost after 4 months. The multivariate discriminant analysis showed the highest
      correlation for implant stability by bridge insertion torque (BIT), localization
      (mandible or maxilla), and implant insertion torque (IIT) as success parameters.
      The loaded implants displayed collagen fibers, which were oriented in a more
      transverse way. In addition, a higher quantity of secondary osteons was present.
      In comparison, the unloaded implants had collagen fibers with a more parallel
      orientation, and a higher quantity of marrow spaces was present. CONCLUSIONS:
      When observed after 4 months, immediately loaded implants showed a higher degree
      of bone formation and remodeling in comparison to unloaded implants. Immediately
      loaded implants also demonstrated a prevalence of transversely oriented collagen
      fibers in the peri-implant bone. In this animal model, an average insertion
      torque of the implants within one bridge>35 Ncm was associated with the most
      successful implants.

PMID- 16460239
TI  - Longitudinal clinical evaluation of adjunct minocycline in the treatment of
      chronic periodontitis.
AB  - BACKGROUND: The clinical benefits of minocycline in combination with thorough
      scaling and root planing (SRP) have been examined in multicenter studies. The aim
      of this longitudinal investigation was to evaluate the clinical response to
      scaling and root planing combined with the use of locally delivered minocycline
      microspheres for 720 days in individuals with advanced chronic periodontitis.
      METHODS: A total of 26 individuals aged 26 to 69 years (mean: 46.8+/-12.1 years)
      were included in this double-blind randomized clinical trial. After
      randomization, 13 individuals were selected for the test group (TG) and treated
      with SRP plus subgingival minocycline at baseline and 90, 180, and 270 days, and
      13 individuals were selected for the control group (CG) and received SRP plus
      vehicle at the same timepoints. Two homologous sites with probing depth (PD)>or=6
      mm were chosen in each subject. To evaluate the clinical response after
      treatment, PD, plaque index (PI), and gingival index (GI) were assessed at
      baseline and 90, 180, 270, 360, and 720 days. RESULTS: No statistical differences
      were found between test and control groups in relation to PD at the different
      timepoints. The mean values of PD demonstrated a higher reduction in the test
      group at 270 and 360 days. No statistical differences were observed at 90, 180,
      and 720 days between TG and CG (P<0.05; Wilcoxon test). There were no
      statistically significant differences between TG and CG concerning PI and GI
      (P<0.05; analysis of variance and t test) at all evaluated timepoints.
      CONCLUSION: Our findings demonstrated that both therapies reduced mean PD from 90
      to 360 days; however, SRP combined with the use of subgingival minocycline showed
      a higher reduction at 270 and 360 days following therapy.

PMID- 16460240
TI  - Bone sialoprotein gene transfer to periodontal ligament cells may not be
      sufficient to promote mineralization in vitro or in vivo.
AB  - BACKGROUND: To improve regenerative therapies, it is important to understand the
      cells and factors modulating periodontal tissues. Our group has focused on bone
      sialoprotein (BSP), a mineralized tissue-selective protein considered to be
      involved in the initiation of cementogenesis and osteogenesis. In this study, we
      examined whether gene transfer of BSP into periodontal ligament (PDL) cells would
      result in an increased ability of PDL cells to promote mineralization in vitro
      and in vivo. METHODS: PDL cells obtained from CD-1 mice were immortalized using
      simian virus (SV) 40 large T antigen (TAg) and designated SV-PDL cells. SV-PDL
      cells were infected in vitro with LacZ gene-expressing control adenovirus vector.
      A 1,000 plaque-forming unit (pfu) titer was selected (based on X-gal staining)
      and cells were infected with mouse BSP-expressing replication-deficient
      adenoviral vector to determine the mRNA expression and protein level of BSP.
      Total RNA was isolated from cells on days 2, 4, and 6. Media were obtained on
      days 3, 5, and 7 for protein determination. Northern blot analysis was performed
      for mRNA expression and Western blot analysis for protein expression. To test the
      effect of BSP gene transfer on the mineralization of PDL cells, in vitro (von
      Kossa) and in vivo (severe combined immunodeficiency [SCID] mice) experiments
      were performed. RESULTS: Under normal conditions, PDL cells do not express BSP
      transcripts and do not promote significant mineralization. SV-PDL cells infected
      with a BSP viral vector expressed and secreted substantial levels of BSP as
      confirmed by Northern and Western blot analysis. BSP mRNA and protein levels were
      strong on day 2 and still apparent on day 6, although not as great. However, no
      mineral nodule formation was noted either in vitro or in vivo. CONCLUSIONS:
      Although BSP is an important and necessary protein for mineralization, it may not
      be sufficient for promoting mineralization without the addition or removal of
      other factors. Further studies will help to clarify the specific factors required
      for promoting mineralization, a required step for designing predictable
      periodontal regenerative therapies.

PMID- 16460241
TI  - Comparative 6-month clinical study of a semilunar coronally positioned flap and
      subepithelial connective tissue graft for the treatment of gingival recession.
AB  - BACKGROUND: The purpose of this randomized clinical trial was to compare the
      outcome of gingival recession therapy using the semilunar coronally positioned
      flap (SCPF) or the subepithelial connective tissue graft (SCTG). METHODS:
      Seventeen patients with bilateral Miller Class I buccal gingival recessions
      (<or=4 mm) in maxillary canines or premolars were selected. The recessions were
      randomly assigned to receive either the SCPF or the SCTG. Recession height (RH),
      recession width (RW), width of keratinized tissue (WKT), thickness of keratinized
      tissue (TKT), probing depth (PD), and clinical attachment level (CAL) were
      measured at baseline and 6 months post-surgery. Patient satisfaction with
      esthetics, root sensitivity, and postoperative pain was also evaluated. RESULTS:
      The average percentages of root coverage for SCPF and SCTG were 90.95% and 96.10%
      (P<0.05), respectively, and the complete root coverage observed was 52.94% and
      76.47%, respectively. The SCTG showed a statistically significant increase in TKT
      (P<0.05). There were no significant differences between the two groups with
      regard to RH, RW, WKT, PD, and CAL. The esthetic condition after both treatments
      was considered satisfactory by the patients. CONCLUSION: The findings from this
      study indicate that SCPF and SCTG can be successfully used to treat Class I
      gingival recession.

PMID- 16460242
TI  - Periodontitis is associated with preeclampsia in pregnant women.
AB  - BACKGROUND: Recent investigations have demonstrated a positive association
      between periodontitis and pregnancy complications. The purpose of this study was
      to determine the effect of periodontitis and the subgingival microbial
      composition on preeclampsia. METHODS: A case-control study was carried out in
      Cali, Colombia that included 130 preeclamptic and 243 non-preeclamptic women
      between 26 to 36 weeks of pregnancy. Sociodemographic data, obstetric risk
      factors, periodontal status, and subgingival microbial composition were
      determined in both groups. Preeclampsia was defined as blood pressure>or=140/90
      mm Hg, and >or=2+ proteinuria, confirmed by 0.3 g proteinuria/24 hours of urine
      specimens. Controls were healthy pregnant women. Odds ratios (ORs) for
      periodontitis and subgingival microbiota compositions were calculated. RESULTS: A
      total of 83 out of 130 preeclamptic women (63.8%) and 89 out of 243 controls
      (36.6%) had chronic periodontitis (OR: 3.0; 95% confidence interval (CI): 1.91 to
      4.87; P<0.001). Clinical attachment loss increased in the case group (4.0+/-0.10
      mm) compared to the control group (3.0+/-0.08 mm) (P<0.001). The average newborn
      birth weight from preeclamptic mothers was 2.453 g, whereas in controls was 2.981
      g (P<0.001). Two red complex microorganisms, Porphyromonas gingivalis and
      Tannerella forsythensis, and the green complex microorganism Eikenella corrodens
      were more prevalent in the preeclamptic group than in controls (P<0.01).
      CONCLUSIONS: Chronic periodontal disease and the presence of P. gingivalis, T.
      forsythensis, and E. corrodens were significantly associated with preeclampsia in
      pregnant women. Further research is needed to establish pathogenic mechanisms of
      active periodontal disease and subgingival periodontopathogens related to
      preeclampsia development.

PMID- 16460243
TI  - Collagenases in gingival crevicular fluid in type 1 diabetes mellitus.
AB  - BACKGROUND: Studies have demonstrated that high levels of collagenase activity in
      gingival crevicular fluid (GCF) are associated with degradation of periodontal
      tissues in progressive periodontitis compared to periodontally healthy tissues.
      Because the activation of collagenases is an important issue in periodontitis, we
      have studied the activation of collagenase in gingival crevicular fluid samples
      of diabetic patients. METHODS: Collagenase activity was studied in human gingival
      crevicular fluids. Twenty-two poorly controlled diabetic patients (e.g., blood
      glucose: 11.0+/-0.7 mmol/l; hemoglobin A1c [HbA1c]: 9.6%+/-0.3%) and five well
      controlled diabetic patients were compared to six chronic periodontitis subjects
      and five healthy controls. Collagenase activity against type I collagen was
      measured using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis
      quantitated by laser densitometry. RESULTS: The poorly controlled diabetic
      patients had more alveolar bone loss than the well-controlled diabetic subjects
      and controls (P<0.001; t test). The activity of collagenases in GCF in poorly
      controlled diabetic patients was similar to that seen in chronic periodontitis
      subjects (P>0.05) but higher than in healthy controls (P<0.01; t test), whereas
      there was no difference between the well-controlled diabetic subjects and
      systemically healthy controls (P>0.05; t test). CONCLUSION: Poorly controlled
      diabetes is strongly related to periodontal tissue destruction, and collagenases
      in GCF may mediate and reflect this effect.

PMID- 16460244
TI  - Comparative study of two root coverage procedures: a 24-month follow-up
      multicenter study.
AB  - BACKGROUND: Treatment alternatives to cover exposed root surfaces include free
      grafts, pedicle flaps, and barrier membranes. This 24-month follow-up study
      clinically evaluated the long-term effect of a coronally advanced flap procedure
      with the additional use of enamel matrix derivative (EMD) to treat gingival
      recession versus the subpedicle connective tissue graft (CTG) procedure. METHODS:
      Miller Class I or II buccal recession-type defects in the anterior teeth or
      premolars in 65 patients (28 in EMD and 37 in CTG groups) were treated in several
      centers. At baseline and 12 and 24 months post-treatment, vertical recession
      defect (VRD), height of keratinized tissue (HKT), and probing depth (PD) were
      recorded, and the percentage of root coverage (PRC) of the original defect was
      calculated. Student t test, analysis of variance, and analysis of covariance were
      used for statistical analyses. RESULTS: At 12- and 24-month evaluations, PRC was
      73.2% (SD=15.58%) and 76.9% (SD=16.77%) in the EMD group and 86.8% (SD=12.48%)
      and 84.3% (SD=13.32%) in the CTG group, respectively (P<0.001). Differences
      between groups were statistically significant (P=0.002). Baseline HKT was 1.07 mm
      (SD=0.66 mm) in the EMD group and 1.65 mm (SD=0.92 mm) in the CTG group. At 12
      and 24 months, values were 1.75 mm (SD=0.59 mm) and 2.25 mm (SD=0.52 mm) in the
      EMD group and 4.24 mm (SD=0.89 mm) and 4.05 mm (SD=0.94 mm) in the CTG group,
      respectively. Differences in HKT were statistically significant within (EMD:
      P<0.001; CTG: P=0.017) and between (P<0.001) groups. CONCLUSIONS: Both treatments
      proved clinically successful. CTG treatment showed a higher percentage of root
      coverage and HKT increase. EMD is a valuable, long-term effective treatment
      alternative to achieve root coverage together with an increase in HKT.

PMID- 16460245
TI  - Long-term evaluation of hollow screw and hollow cylinder dental implants:
      clinical and radiographic results after 10 years.
AB  - BACKGROUND: In 1988, an implant manufacturer offered a new dental implant system,
      with a wide choice of hollow cylinder (HC) and hollow screw (HS) implants. The
      purpose of this retrospective study of HS and HC implants was to evaluate
      clinical and radiographic parameters of peri-implant tissue and to analyze
      surgical and prosthetic aftercare. METHODS: A total of 89 HS and 26 HC implants
      in 38 edentulous patients were available for complete evaluation. The patients
      were treated with overdentures stabilized by two or four implants. The follow-up
      period was 10 years. RESULTS: The results of the clinical evaluation showed a
      mean sulcus probing depth of 3.3+/-1.3 mm (range=2 to 10 mm). The mean
      radiographic bone loss was 2.2+/-2.1 mm (range=0.1 to 12.2 mm). One implant (HS)
      was removed during the osseointegration period. Three other implants (two HS and
      one HC) in three patients had to be removed after 10 years. The survival rate of
      the HS implant (96.6%) was comparable to the HC implant (96.1%). The success rate
      of the HS implant (93.3%) was slightly more favorable compared to the HC implant
      (88.5%). The HS and HC implants met the Albrektsson criteria of success.
      CONCLUSIONS: HS and HC implants provide a stable base for long-term support of a
      mandibular overdenture. Furthermore, it is important to monitor peri-implant bone
      level by taking annual radiographs and measuring probing depth, especially after
      prolonged service.

PMID- 16460246
TI  - Povidone-iodine used as an adjunct to non-surgical treatment of furcation
      involvements.
AB  - BACKGROUND: The aim of this clinical trial was to evaluate the effect of
      topically applied povidone-iodine (polyvinylpyrrolidone and iodine [PVP-I]) used
      as an adjunct to non-surgical therapy of furcation involvements. METHODS: Forty
      four patients presenting at least one Class II furcation involvement that bled on
      probing with probing depth (PD)>or=5 mm were recruited. Patients were stratified
      into two treatment groups: 1) subgingival instrumentation by an ultrasonic device
      using PVP-I (10%) as the cooling liquid (test); and 2) identical treatment using
      distilled water as the cooling liquid (control). The following clinical outcomes
      were evaluated: plaque index, bleeding on probing (BOP), position of the gingival
      margin, relative attachment level (RAL), PD, and relative horizontal attachment
      level (RHAL). The N-benzoyl-L-arginine-p-nitroanilide (BAPNA) test was used to
      analyze the trypsin-like activity in dental biofilm. The clinical and biochemical
      parameters were evaluated at baseline and 1, 3, and 6 months after therapy.
      RESULTS: Both groups had similar means of PD reduction and RAL and RHAL gain. At
      6 months, these variables were, respectively, 2.31, 1.17, and 1.00 mm in the
      control group and 2.31, 1.23, and 1.02 mm in the test group. There was also no
      difference between groups regarding the number of furcation sites presenting RAL
      gain>or=2 mm. The results of the BAPNA test failed to demonstrate significant
      differences between groups. CONCLUSION: Non-surgical therapy can effectively
      treat Class II furcation involvements, and the use of topically applied PVP-I as
      an adjunct to subgingival instrumentation does not provide additional benefits.

PMID- 16460247
TI  - Er:YAG laser scaling of diseased root surfaces: a histologic study.
AB  - BACKGROUND: The aim of the present study was to observe the effects of an erbium
      doped:yttrium, aluminum, and garnet (Er:YAG) laser when used to treat
      periodontally involved root surfaces. METHODS: Forty teeth affected by severe
      periodontal disease and scheduled for extraction were divided into two groups: in
      group A (control), 20 teeth were treated by hand instrumentation, and in group B
      (test), 20 teeth were treated by Er:YAG laser. RESULTS: In group A (teeth treated
      by curets), the root cementum layer was completely removed, but many deep
      scratches on the dentin layer were also observed. In group B, the laser-treated
      root surfaces, there was no cracking or carbonization, and the bacterial flora
      was completely eliminated, leaving a rough and uniform surface. CONCLUSION:
      Results of the present study showed that clinical use of an Er:YAG laser in vivo
      achieves plaque and calculus removal, providing a rough surface morphology.

PMID- 16460248
TI  - Compliance as a prognostic indicator: retrospective study of 505 patients treated
      and maintained for 15 years.
AB  - BACKGROUND: The relationship of patient compliance to overall tooth prognosis
      remains controversial. There are little data, often conflicting, that pertain to
      tooth loss as a function of patient compliance. METHODS: This retrospective study
      evaluates the impact of compliance (complete versus erratic) on common
      periodontal clinical variables, such as probing depth, bleeding index, plaque
      index, and tooth loss for 505 patients in a long-term period of observation (15
      to 23 years) and maintenance therapy (at least 10 years). Compliance was defined
      in two ways for all analyses. Under the definition for compliance 1, patients who
      missed <30% of all prescribed maintenance visits were classified as complete
      compliers. Under the definition for compliance 2, patients who never went 2 years
      without a maintenance visit were classified as complete compliers. Change in
      clinical variables was dichotomized into reduction in plaque index versus no
      reduction, reduction in bleeding on probing versus no reduction, reduction in the
      percentage of periodontal pockets>3 mm versus no reduction, no increase in
      decayed, missing, or filled teeth (DMFT) versus increase, and no tooth loss
      versus tooth loss. The effects of both definitions of compliance were then
      evaluated in a series of multiple logistic regression models with adjustment for
      potential confounders. RESULTS: The analysis of the dichotomous change in
      clinical parameters over time revealed that complete compliers tended to show
      reduction in bleeding on probing and reduction in plaque index compared to
      erratic compliers for both definitions of compliance. In contrast, complete
      compliers under compliance 2 were less likely to have a reduction in the
      percentage of periodontal pockets >3 mm compared to erratic compliers, whereas
      complete compliers under compliance 1 had about the same likelihood of
      demonstrating a reduction in periodontal pockets compared to erratic compliers
      under this classification scheme. Under both definitions for compliance, complete
      compliers were more likely to exhibit tooth loss than erratic compliers, with the
      greatest tooth loss exhibited by complete compliers under the definition for
      compliance 1. CONCLUSIONS: Based on these results, complete compliers under both
      definitions tended to show a reduction in plaque and bleeding on probing over
      time. However, change in periodontal pockets and DMFT over time varied according
      to the definition of compliance that was used. In addition, the results seem to
      indicate that the decision for tooth extraction made by dental health
      professionals at maintenance visits may result in greater tooth loss.

PMID- 16460249
TI  - Description of two new cathepsin C gene mutations in patients with Papillon
      Lefevre syndrome.
AB  - BACKGROUND: Papillon-Lefevre syndrome (PLS) is a rare autosomal disorder
      characterized by severe periodontitis and palmar plantar hyperkeratosis (PPK).
      PLS is caused by mutations in the cathepsin C (CTSC) gene. Dipeptidyl peptidase I
      (DPPI) encoded by the CTSC locus removes dipeptides from the amino terminus of
      the protein substrate and mainly plays an important role in immune and
      inflammatory processes. Several mutations have been reported in this gene in
      patients with PLS. This study reports two novel deletion mutation of the CTSC
      gene in two Indian families with PLS. METHODS: Peripheral blood samples were
      obtained for genomic DNA isolation from individuals belonging to two Indian
      families. Exon-specific intronic primers were used to amplify DNA from all
      individuals, and the PCR products were subsequently sequenced to detect the
      mutations. Heteroduplex analysis (HDA) was used to confirm heterozygosity and to
      determine the presence of mutations in control individuals. RESULTS: All patients
      from both families had a classic PLS phenotype, which included PPK and severe
      periodontitis. Sequence analysis of the CTSC gene revealed two novel deletion
      mutations, one (1213-1215delCAT) in exon 7 and the other (629-630delGA) in exon 4
      of the CTSC gene. For both mutations, the patients were homozygous, whereas the
      parents were heterozygous. CONCLUSIONS: This study reports two novel deletion
      mutations in two Indian families with PLS. One of the mutations introduces a
      premature stop codon, thereby producing a truncated protein. In the other case,
      the mutation observed leads to the loss of a highly conserved histidine molecule
      that is present in the active site of the enzyme. In both cases, mutations may
      result in a conformation change, causing loss of the enzymatic activity.

PMID- 16460250
TI  - Phenotypic study of human gingival fibroblasts labeled with superparamagnetic
      anionic nanoparticles.
AB  - BACKGROUND: A specific labeler of the human gingival fibroblast (HGF) does not
      exist. Anionic maghemite nanoparticles allow labeling of a wide cell variety and
      their recognition in cellular, organotypical, and animal models. METHODS: We
      studied internalization effects of nanoparticles on an HGF phenotype in vitro,
      evaluating transcription and secretion of connective tissue remodeling molecules,
      i.e., matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases
      (TIMPs), and cytokines controlling their activation/inhibition, i.e.,
      transforming growth factor-beta (TGF-beta1), tumor necrosis factor-alpha (TNF
      alpha), and interleukins 1beta and 4 (IL-1beta and IL-4). After proliferation
      kinetics, cellular uptake was studied by Perls coloration and magnetophoresis on
      labeled culture. Dot blotting, Western blotting, and zymography were used to
      detect MMP-1, -2, and -3 and TIMP-1 and -2 secretions in culture supernatants,
      and reverse transcription-polymerase chain reaction (RT-PCR) was performed to
      detect the mRNA expression of these molecules. Enzyme-linked immunosorbent assay
      (ELISA) tests were used to determine TGF-beta1, TNF-alpha, IL-1beta, and IL-4
      levels. RESULTS: Our data indicated high (15.3+/-5.8 pg/cell) but heterogeneous
      distribution of nanoparticles in HGF. Twenty-four hours after labeling, MMP-1, 
      2, and -3 and TIMP-2 secretion increased (P<0.001) with RT-PCR confirmation at 12
      hours, whereas TIMP-1 did not. IL-1beta increased at day 1 (D1) (P<0.001) and IL
      4 at D3 (P<0.01), but not TGF-beta1 or TNF-alpha. CONCLUSIONS: After labeling
      with these maghemite nanoparticles, HGF increased secretion of IL-1beta at D1,
      probably inducing the increase of MMP-1, -2, and -3 and TIMP-2. The increase of
      IL-4 secretion began with the decreased synthesis of MMPs and TIMPs at D3.
      Despite this transitory inflammatory reaction at 3 days following
      internalization, maghemite nanoparticles did not affect HGF phenotype, thereby
      authorizing their use as labelers.

PMID- 16460251
TI  - The effects of antimicrobial sprays and mouthrinses on supragingival plaque
      regrowth: a comparative study.
AB  - BACKGROUND: Due to the side effects of chlorhexidine digluconate (CHX)
      mouthrinsing, a spray has been proposed as an alternative method of CHX delivery
      to the oral cavity. The aim of this study was to investigate the plaque
      inhibitory effects of CHX, cetylpyridinium chloride (CPC), and triclosan (TRN)
      delivered by sprays and mouthrinses. METHODS: The study was an observer-masked,
      randomized cross-over design balanced for carryover effects, involving 15 healthy
      volunteers in a 4-day plaque regrowth model. Products being tested (0.2% CHX,
      0.12% CHX, 0.05% CPC, and 0.03% TRN) were used both as sprays and mouthrinses. A
      saline solution served as a negative control. On day 1, subjects received
      professional prophylaxis, suspended oral hygiene measures, and commenced using
      their allocated products. On day 5, subjects were scored for disclosed plaque.
      RESULTS: CHX sprays (P<0.01) were the most effective sprays in preventing plaque
      regrowth, without significant differences between the two concentrations tested
      (P>0.05). TRN spray showed a significant inhibition of plaque regrowth in
      comparison to the negative control (P<0.05). CPC spray did not differ from saline
      spray (P>0.05). A similar trend of efficacy was detected for rinses. Although the
      effect on plaque regrowth observed with CHX rinses was superior to that of CHX
      sprays (P<0.0003), the latter did not cause side effects (P>0.2). CONCLUSIONS:
      These findings, together with those from clinical trials, suggest that the CHX
      containing sprays may represent an effective alternative to CHX rinses when
      mechanical oral hygiene has to be avoided in restricted areas. On the contrary,
      the TRN and CPC sprays showed little or no plaque inhibitory effects.

PMID- 16460252
TI  - A systematic review on the effects of the chlorhexidine chip when used as an
      adjunct to scaling and root planing in the treatment of chronic periodontitis.
AB  - BACKGROUND: Several local antimicrobial agents, such as a bioabsorbable
      chlorhexidine chip, have been developed to enhance the outcome of non-surgical
      periodontal therapy. METHODS: Electronic (MEDLINE and Cochrane Oral Health Group
      Specialized Trials Register) and manual searches were performed to detect studies
      concerning the use of the chlorhexidine chip as an adjunct to scaling and root
      planing in the treatment of chronic periodontitis. Only full-text randomized
      controlled trials published in English up to June 2005 were included. RESULTS:
      Five studies were finally selected following independent screening by two
      reviewers. Due to considerable heterogeneity in study design, a qualitative data
      analysis was performed. Multicenter studies have indicated significantly higher
      pocket reductions and clinical attachment gains following a combination of
      mechanical debridement and repeated chlorhexidine chip administration in
      comparison to scaling and root planing alone. However, some recent studies failed
      to confirm the additional value of the chlorhexidine chip. A number of interstudy
      disparities with respect to methodological quality and study design may account
      for this lack of accordance. CONCLUSIONS: The clinical and microbiological data
      currently available on the chlorhexidine chip are limited and conflicting. More
      research is needed to elucidate the additional value of the chlorhexidine chip
      when used as an adjunct to scaling and root planing.

PMID- 16460253
TI  - A morphologic comparison of gingival changes influenced by cyclosporin and
      tacrolimus in rats: an experimental study.
AB  - BACKGROUND: The aim of this study was to compare the morphologic changes in the
      gingiva brought about by the administration of cyclosporin and tacrolimus in
      rats. METHODS: The study was conducted on 30 six-week-old male Sprague-Dawley
      rats, divided into three groups of 10 rats each, for a period of 4 weeks. Group I
      rats received cyclosporin (30 mg/kg body weight), and group II rats received
      tacrolimus (1.5 mg/kg body weight), by means of a gavage. Group III served as
      control and received olive oil alone. Impressions of the mandibular incisal
      region were made weekly, and stone casts were prepared for measuring morphologic
      changes of the gingiva. RESULTS: An increase in the measured gingival dimensions
      was observed in the test groups as early as week 2 after the commencement of drug
      administration. Intergroup comparison revealed that the increase in the measured
      dimensions was greater in group I than group II at the end of 4 weeks.
      CONCLUSIONS: Cyclosporin and tacrolimus were capable of causing gingival
      enlargement in Sprague-Dawley rats. However, the magnitude of tacrolimus
      influenced gingival enlargement seemed to be comparatively less than cyclosporin.

PMID- 16460254
TI  - Inhibition of proinflammatory activities of major periodontal pathogens by
      aqueous extracts from elder flower (Sambucus nigra).
AB  - BACKGROUND: Prolonged induction of excessive levels of inflammatory mediators
      contributes to the pathogenesis of chronic disease states, such as periodontitis.
      It is thus important to develop safe and effective anti-inflammatory strategies
      for therapeutic reasons. In this study, we determined the ability of aqueous
      extracts from elder flower (Sambucus nigra) to inhibit the proinflammatory
      activity of major virulence factors from the periodontal pathogens Porphyromonas
      gingivalis and Actinobacillus actinomycetemcomitans. METHODS:
      Monocytes/macrophages or neutrophils were incubated with whole cells of P.
      gingivalis, A. actinomycetemcomitans, or purified components thereof
      (lipopolysaccharide and fimbriae) in the absence or presence of elder flower
      extract and were assayed for cytokine production, integrin activation, or
      induction of the oxidative burst. RESULTS: The elder flower extract was found to
      potently inhibit all proinflammatory activities tested. Investigation of the
      underlying mechanisms revealed that the anti-inflammatory extract inhibited
      activation of the nuclear transcription factor kappaB and of phosphatidylinositol
      3-kinase. CONCLUSION: The elder flower extract displays useful anti-inflammatory
      properties that could be exploited therapeutically for the control of
      inflammation in human periodontitis.

PMID- 16460255
TI  - Periodontal and hematological characteristics associated with aggressive
      periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis.
AB  - BACKGROUND: Periodontitis shares several clinical and pathogenic characteristics
      with chronic arthritis, and there is some degree of coexistence. The aims of this
      study were to elucidate whether patients with localized aggressive periodontitis
      (LAgP), generalized aggressive periodontitis (GAgP), juvenile idiopathic
      arthritis (JIA), and rheumatoid arthritis (RA) share periodontal and
      hematological characteristics distinguishing them from individuals free of
      diseases. METHODS: The study population consisted of white adults (<or=35 years
      old) with LAgP (N=18), GAgP (N=27), JIA (N=10), RA (N=23), and healthy controls
      (N=25). All individuals underwent a standardized interview, blood sampling, and
      an intraoral examination, including registration of plaque, bleeding on probing,
      probing depth (PD), clinical attachment loss (CAL), and alveolar bone loss (ABL)
      on radiographs. Blood samples were analyzed for erythrocyte fraction, leukocytes
      and differential counts, erythrocyte sedimentation rate, C-reactive protein
      (CRP), immunoglobulin (Ig) M and IgA rheumatoid factors (RFs), and antibodies to
      cyclic citrullinated peptides. RESULTS: RA patients had a higher percentage of
      sites with PD>or=4 mm, CAL>or=2 mm, and ABL>or=2 mm compared to controls. The
      percentage of sites with CAL>or=2 mm significantly correlated with the levels of
      IgM-RF and IgA-RF. Missing teeth in JIA and RA patients were not lost due to
      periodontitis. Patients with GAgP showed higher levels of leukocytes, including
      neutrophils, and CRP compared to controls. In part, JIA and RA patients showed
      similar results. CONCLUSIONS: Young adults with RA may develop periodontal
      destruction, and these patients require professional attention. Both differences
      and similarities in periodontal and hematological variables were seen in
      individuals with periodontitis, JIA, and RA.

PMID- 16460256
TI  - Increased intake of dairy products is related to lower periodontitis prevalence.
AB  - BACKGROUND: An inverse association between calcium intake and periodontitis
      prevalence was recently reported. Dairy products are rich sources of calcium and
      other important nutrients. To date, it appears that the relationship between the
      intake of dairy products and periodontitis has not been investigated. The purpose
      of the present study was to examine whether or not there is an association
      between the intake of dairy products and periodontitis prevalence. METHODS: A
      total of 12,764 individuals who participated in the Third National Health and
      Nutrition Examination Survey were included in this study. Individuals who had at
      least one site with an attachment loss>or=3 mm and a probing depth>or=4 mm were
      considered to have periodontitis. The intake of dairy products was categorized
      into quintiles. Descriptive statistics and logistic regression models were used
      for data analyses. RESULTS: Prevalence of periodontitis was 41% lower for
      individuals in the highest quintile of intake of dairy products than those in the
      lowest quintile (P<0.001 for trend). After adjusting for known and suspected
      periodontitis risk factors (age, gender, race?ethnicity, cigarette smoking,
      education, diabetes, poverty index, vitamin use, body mass index, physical
      activity, time since the last dental visit, dental calculus, and gingival
      bleeding), individuals in the highest quintile of intake of dairy products were
      20% less likely to have periodontitis than those in the lowest quintile (P=0.024
      for trend). CONCLUSIONS: The results of this study showed an inverse association
      between the intake of dairy products and prevalence of periodontitis.
      Longitudinal and/or intervention studies are required to confirm these findings
      and to further examine the impact of a higher intake of dairy products on the
      prevention and treatment of periodontitis.

PMID- 16460258
TI  - Implant placement at the time of maxillary molar extraction: technique and report
      of preliminary results of 83 sites.
AB  - BACKGROUND: The purpose of this study was to evaluate the predictability of
      implant placement at the time of maxillary molar extraction using a modified
      insertion technique and implant design. METHODS: At the time of maxillary molar
      extraction, 83 tapered-end implants with an apical diameter of 4.1 mm and a neck
      diameter of 6.5 mm were placed in maxillary first or second molar sites,
      following manipulation of the remaining interradicular bone with osteotomes.
      Regenerative materials, consisting of demineralized freeze-dried bone allograft
      (DFDBA) and/or osseous coagulum, and bioabsorbable or non-resorbable membranes
      were placed, and passive soft-tissue primary closure was attained in all cases.
      RESULTS: Soft-tissue closure was maintained until the time of clinical reentry 6
      months after implant insertion in 81 of 83 sites. Loss of primary soft-tissue
      closure in the other two areas did not result in complete uncovering of the cover
      screw and implant top. All implants were clinically immobile at the time of
      implant uncovery 6 months after insertion and were restored with single crowns.
      All implants were functioning successfully for up to 18 months (mean: 12.4
      months). CONCLUSION: The combination of atraumatic removal of hopeless maxillary
      molars, controlled manipulation of the residual interradicular bone, insertion of
      implants of the aforementioned design, and use of appropriate regenerative
      materials at the time of implant insertion predictably afforded a stable implant
      for restoration with a single crown.

PMID- 16460257
TI  - Five-year follow-up of regenerative periodontal therapy with enamel matrix
      derivative at sites with angular bone defects.
AB  - BACKGROUND: This prospective case series report aimed at analyzing the long-term
      (5 years) stability of clinical attachment level (CAL) gains following
      regenerative therapy with the use of enamel matrix proteins in intrabony defects.
      METHODS: A total of 114 consecutively treated periodontal patients (mean age:
      55.8 years) were initially included. Each subject exhibited at least one deep
      proximal intrabony defect with the inclusion criteria of 1) probing depth
      (PD)>or=5 mm, 2) clinical attachment loss>or=6 mm, and 3) radiographic evidence
      of a >or=3-mm intrabony component. A total of 146 defects met the criteria for
      inclusion. At least 6 months after the completion of an initial phase of
      mechanical infection control, a baseline examination was performed to
      characterize the experimental site. Reconstructive therapy with the use of enamel
      matrix proteins was subsequently performed. Experimental sites were reexamined 1
      and 5 years after reconstructive surgery. Primary efficacy variables were
      considered to be changes in PD, CAL, soft tissue recession (REC), and
      radiographic defect depth (RDD). Stepwise regression analysis was employed for
      evaluation of predicting factors of CAL change between the 1- and 5-year
      reexaminations. RESULTS: A total of 82 patients (102 defects) were included in
      the analysis. One year following the regenerative surgery, a mean CAL gain of 4.3
      mm (P<0.001), a mean PD reduction of 4.9 mm (P<0.001), and a mean increase in REC
      of 0.6 mm (P<0.001) were recorded. At the 5-year follow-up, a further mean PD
      reduction of 0.3 mm (P>0.05), CAL gain of 1.1 mm (P<0.01), and reduction in
      recession of 0.8 mm (P<0.01) had taken place. Radiographs revealed that the bone
      defect had been reduced in depth with an average of 2.9 mm at 1 year (P<0.001).
      No statistically significant alteration in defect depth was observed between 1
      and 5 years of follow-up. The stepwise regression analysis identified the degree
      of REC and residual PD at 1 year as significant predictors of CAL change between
      1 and 5 years. CONCLUSION: Results demonstrated long-term (5 years) stability of
      CAL gains following regenerative therapy with the use of enamel matrix proteins
      in intrabony defects.

PMID- 16460259
TI  - Palatal neurofibroma associated with localized periodontitis.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is the most common form of
      neurofibromatosis. While typically considered a dermatologic disorder, intraoral
      signs of neurofibromatosis occur quite commonly. This clinical entity can be
      confused with periodontitis because of the presence of periodontal pockets. In
      this report, we present the case of a palatal neurofibroma with radiographic
      involvement in a patient with NF1. METHODS: A 40-year-old female patient was
      referred from her general dentist to evaluate advanced periodontitis in the
      maxillary left quadrant. The patient's medical history was significant for a soft
      tissue lesion excised from her back 11 years previously and diagnosed as a
      neurofibroma. Subsequent medical examination at that time confirmed a systemic
      diagnosis of NF1. A comprehensive periodontal evaluation was performed, and
      panoramic and periapical radiographs were taken. Teeth were tested for vitality.
      An incisional biopsy was completed for histopathologic examination. RESULTS: The
      periodontal evaluation revealed the presence of 6 to 9 mm probing depths adjacent
      to teeth #14 and #15. Panoramic and periapical radiographs showed a circumscribed
      0.8x0.9-cm unilocular radiolucency superimposed over the root of tooth #13 and
      extensive horizontal bone loss on the distal side of #15. Incisional biopsy
      confirmed the presence of a neurofibroma, and because of the extent of the
      lesion, the patient was referred to the Oral and Maxillofacial Surgery service
      for complete excision. CONCLUSIONS: Neurofibromas can cause extensive destruction
      of alveolar bone, mimicking periodontitis. Due to the potential systemic and
      genetic implications, the diagnosis of neurofibroma requires appropriate medical
      referral.

PMID- 16460260
TI  - Characterization of patients presenting for treatment to a university refractory
      periodontal diseases unit: three case reports.
AB  - BACKGROUND: Of the many forms of periodontal disease, refractory periodontal
      diseases are the least characterized. They are defined as the continued
      degeneration of the periodontium despite adequate management. This has led to the
      suggestion that there may be a systemic component that is a contributing factor
      to the development of this condition. The objectives of this report were to
      follow the progression of clinical changes associated with periodontal disease
      over a number of years in this unique population and review various hematologic
      and microbiologic factors that may be contributing to the disease progression.
      METHODS: Three subjects were profiled. They were referred to the Refractory
      Periodontal Disease Unit at the University of Toronto by periodontists or general
      practitioners in the Southern Ontario region. Complete medical and dental
      histories were obtained along with baseline clinical measurements. Periodontal
      examinations were facilitated with the use of a computer-assisted periodontal
      probe. A microbiologic analysis using immunofluorescence techniques was able to
      detect Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and
      Actinobacillus actinomycetemcomitans and spirochetes. A hematologic analysis,
      including a complete blood count (CBC), immune profile, and glycosylated
      hemoglobin assay, was also performed. RESULTS: The clinical presentation revealed
      that patients receiving adequate maintenance therapy and with good to excellent
      oral hygiene demonstrated sites with continual loss of attachment. Few
      periodontal pathogens were detected. However, the most significant finding
      appeared to be the report elevated levels of CD8+ cells within this group of
      patients compared to normal laboratory ranges. CONCLUSIONS: This report is an
      attempt at characterizing a unique population within the periodontal realm. The
      long-term monitoring of these patients allowed for an assessment of factors that
      may be involved in the continued decline of the periodontal health of these
      patients. Based on the immune profile, it is possible that a hyperresponsive
      state may be the primary feature of this population. Future assessments,
      including full-mouth interleukin (IL)-1 and matrix metalloproteinase (MMP)-8
      levels, may assist in characterizing this population further, with the goal of
      producing markers that will assist clinicians in predicting treatment outcome.

PMID- 16460261
TI  - Re: Impact of local adjuncts to scaling and root planing in periodontal disease
      therapy: a systematic review. Bonito AJ, Lux L, Lohr KN (2005;76:1227-1236).

PMID- 16460262
TI  - Re: Receptor for advanced glycation end product (RAGE) upregulation in human
      gingival fibroblasts incubated with nornicotine. Katz J, Caudle RM, Bhattacharyya
      I, Stewart CM, Cohen DM (2005;76:1171-1174).

PMID- 16460265
TI  - Cardiac regeneration: repopulating the heart.
AB  - Many forms of pediatric and adult heart disease result from a deficiency in
      cardiomyocyte number. Through repopulation of the heart with new cardiomyocytes
      (that is, induction of regenerative cardiac growth), cardiac disease potentially
      can be reversed, provided that the newly formed myocytes structurally and
      functionally integrate in the preexisting myocardium. A number of approaches have
      been utilized to effect regenerative growth of the myocardium in experimental
      animals. These include interventions aimed at enhancing the ability of
      cardiomyocytes to proliferate in response to cardiac injury, as well as
      transplantation of cardiomyocytes or myogenic stem cells into diseased hearts.
      Here we review efforts to induce myocardial regeneration. We also provide a
      critical review of techniques currently used to assess cardiac regeneration and
      functional integration of de novo cardiomyocytes.

PMID- 16460267
TI  - Protecting the pump: controlling myocardial inflammatory responses.
AB  - Because of the anatomy, function, and nonregenerative nature of the myocardium,
      inflammation in this tissue is not well tolerated. Nevertheless, various diseases
      of the heart are characterized by inflammatory responses involving the effector
      mechanisms of innate and adaptive (lymphocyte-dependent) immunity. The innate
      immune response to ischemia-reperfusion injury is, by far, the most common cause
      of myocardial inflammation. Innate responses may have beneficial influences that
      preserve myocardial function in the short term but may be maladaptive in chronic
      states. Adaptive responses in the myocardium occur with infection or loss of
      tolerance, and lead to myocarditis. Given the narrow margin for benefit of
      cardiac inflammation, special regulatory mechanisms likely raise the threshold,
      compared to other tissues, for the induction and persistence of adaptive immune
      responses. These mechanisms include strong central and peripheral T cell
      tolerance to heart antigens and induction of anti-inflammatory feedback
      mechanisms involving cytokines such as interferon-gamma.

PMID- 16460266
TI  - Endothelial-cardiomyocyte interactions in cardiac development and repair.
AB  - Communication between endothelial cells and cardiomyocytes regulates not only
      early cardiac development but also adult cardiomyocyte function, including the
      contractile state. In the normal mammalian myocardium, each cardiomyocyte is
      surrounded by an intricate network of capillaries and is next to endothelial
      cells. Cardiomyocytes depend on endothelial cells not only for oxygenated blood
      supply but also for local protective signals that promote cardiomyocyte
      organization and survival. While endothelial cells direct cardiomyocytes,
      cardiomyocytes reciprocally secrete factors that impact endothelial cell
      function. Understanding how endothelial cells communicate with cardiomyocytes
      will be critical for cardiac regeneration, in which the ultimate goal is not
      simply to improve systolic function transiently but to establish new myocardium
      that is both structurally and functionally normal in the long term.

PMID- 16460268
TI  - Transcription factors and congenital heart defects.
AB  - Although there have been important advances in diagnostic modalities and
      therapeutic strategies for congenital heart defects (CHD), these malformations
      still lead to significant morbidity and mortality in the human population. Over
      the past 10 years, characterization of the genetic causes of CHD has begun to
      elucidate some of the molecular causes of these defects. Linkage analysis and
      candidate-gene approaches have been used to identify gene mutations that are
      associated with both familial and sporadic cases of CHD. Complementation of the
      human studies with developmental studies in mouse models provides information for
      the roles of these genes in normal development as well as indications for disease
      pathogenesis. Biochemical analysis of these gene mutations has provided further
      insight into the molecular effects of these genetic mutations. Here we review
      genetic, developmental, and biochemical studies of six cardiac transcription
      factors that have been identified as genetic causes for CHD in humans.

PMID- 16460269
TI  - From mice to men: insights into the insulin resistance syndromes.
AB  - The insulin resistance syndrome refers to a constellation of findings, including
      glucose intolerance, obesity, dyslipidemia, and hypertension, that promote the
      development of type 2 diabetes, cardiovascular disease, cancer, and other
      disorders. Defining the pathophysiological links between insulin resistance, the
      insulin resistance syndrome, and its sequelae is critical to understanding and
      treating these disorders. Over the past decade, two approaches have provided
      important insights into how changes in insulin signaling produce the spectrum of
      phenotypes associated with insulin resistance. First, studies using tissue
      specific knockouts or tissue-specific reconstitution of the insulin receptor in
      vivo in mice have enabled us to deconstruct the insulin resistance syndromes by
      dissecting the contributions of different tissues to the insulin-resistant state.
      Second, in vivo and in vitro studies of the complex network of insulin signaling
      have provided insight into how insulin resistance can develop in some pathways
      whereas insulin sensitivity is maintained in others. These data, taken together,
      give us a framework for understanding the relationship between insulin resistance
      and the insulin resistance syndromes.

PMID- 16460270
TI  - LXRS and FXR: the yin and yang of cholesterol and fat metabolism.
AB  - Liver X receptors (LXRs) and farnesoid X receptor (FXR) are nuclear receptors
      that function as intracellular sensors for sterols and bile acids, respectively.
      In response to their ligands, these receptors induce transcriptional responses
      that maintain a balanced, finely tuned regulation of cholesterol and bile acid
      metabolism. LXRs also permit the efficient storage of carbohydrate- and fat
      derived energy, whereas FXR activation results in an overall decrease in
      triglyceride levels and modulation of glucose metabolism. The elegant, dual
      interplay between these two receptor systems suggests that they coevolved to
      constitute a highly sensitive and efficient system for the maintenance of total
      body fat and cholesterol homeostasis. Emerging evidence suggests that the tissue
      specific action of these receptors is also crucial for the proper function of the
      cardiovascular, immune, reproductive, endocrine pancreas, renal, and central
      nervous systems. Together, LXRs and FXR represent potential therapeutic targets
      for the treatment and prevention of numerous metabolic and lipid-related
      diseases.

PMID- 16460271
TI  - Design and function of superfast muscles: new insights into the physiology of
      skeletal muscle.
AB  - Superfast muscles of vertebrates power sound production. The fastest, the
      swimbladder muscle of toadfish, generates mechanical power at frequencies in
      excess of 200 Hz. To operate at these frequencies, the speed of relaxation has
      had to increase approximately 50-fold. This increase is accomplished by
      modifications of three kinetic traits: (a) a fast calcium transient due to
      extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and
      parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in
      troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster
      than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although
      these three modifications permit swimbladder muscle to generate mechanical work
      at high frequencies (where locomotor muscles cannot), it comes with a cost: The
      high g causes a large reduction in attached force-generating cross-bridges,
      making the swimbladder incapable of powering low-frequency locomotory movements.
      Hence the locomotory and sound-producing muscles have mutually exclusive designs.

PMID- 16460272
TI  - The comparative physiology of food deprivation: from feast to famine.
AB  - The ability of animals to survive food deprivation is clearly of considerable
      survival value. Unsurprisingly, therefore, all animals exhibit adaptive
      biochemical and physiological responses to the lack of food. Many animals inhabit
      environments in which food availability fluctuates or encounters with appropriate
      food items are rare and unpredictable; these species offer interesting
      opportunities to study physiological adaptations to fasting and starvation. When
      deprived of food, animals employ various behavioral, physiological, and
      structural responses to reduce metabolism, which prolongs the period in which
      energy reserves can cover metabolism. Such behavioral responses can include a
      reduction in spontaneous activity and a lowering in body temperature, although in
      later stages of food deprivation in which starvation commences, activity may
      increase as food-searching is activated. In most animals, the gastrointestinal
      tract undergoes marked atrophy when digestive processes are curtailed; this
      structural response and others seem particularly pronounced in species that
      normally feed at intermittent intervals. Such animals, however, must be able to
      restore digestive functions soon after feeding, and these transitions appear to
      occur at low metabolic costs.

PMID- 16460273
TI  - Oxidative stress in marine environments: biochemistry and physiological ecology.
AB  - Oxidative stress-the production and accumulation of reduced oxygen intermediates
      such as superoxide radicals, singlet oxygen, hydrogen peroxide, and hydroxyl
      radicals-can damage lipids, proteins, and DNA. Many disease processes of clinical
      interest and the aging process involve oxidative stress in their underlying
      etiology. The production of reactive oxygen species is also prevalent in the
      world's oceans, and oxidative stress is an important component of the stress
      response in marine organisms exposed to a variety of insults as a result of
      changes in environmental conditions such as thermal stress, exposure to
      ultraviolet radiation, or exposure to pollution. As in the clinical setting,
      reactive oxygen species are also important signal transduction molecules and
      mediators of damage in cellular processes, such as apoptosis and cell necrosis,
      for marine organisms. This review brings together the voluminous literature on
      the biochemistry and physiology of oxidative stress from the clinical and plant
      physiology disciplines with the fast-increasing interest in oxidative stress in
      marine environments.

PMID- 16460275
TI  - Interstitial cells of cajal as pacemakers in the gastrointestinal tract.
AB  - In the gastrointestinal tract, phasic contractions are caused by electrical
      activity termed slow waves. Slow waves are generated and actively propagated by
      interstitial cells of Cajal (ICC). The initiation of pacemaker activity in the
      ICC is caused by release of Ca2+ from inositol 1,4,5-trisphosphate (IP3) receptor
      operated stores, uptake of Ca2+ into mitochondria, and the development of unitary
      currents. Summation of unitary currents causes depolarization and activation of a
      dihydropyridine-resistant Ca2+ conductance that entrains pacemaker activity in a
      network of ICC, resulting in the active propagation of slow waves. Slow wave
      frequency is regulated by a variety of physiological agonists and conditions, and
      shifts in pacemaker dominance can occur in response to both neural and nonneural
      inputs. Loss of ICC in many human motility disorders suggests exciting new
      hypotheses for the etiology of these disorders.

PMID- 16460276
TI  - Signaling for contraction and relaxation in smooth muscle of the gut.
AB  - Phosphorylation of Ser19 on the 20-kDa regulatory light chain of myosin II
      (MLC20) by Ca2+/calmodulin-dependent myosin light-chain kinase (MLCK) is
      essential for initiation of smooth muscle contraction. The initial [Ca2+]i
      transient is rapidly dissipated and MLCK inactivated, whereas MLC20 and muscle
      contraction are well maintained. Sustained contraction does not reflect Ca2+
      sensitization because complete inhibition of MLC phosphatase activity in the
      absence of Ca2+ induces smooth muscle contraction. This contraction is suppressed
      by staurosporine, implying participation of a Ca2+-independent MLCK. Thus,
      sustained contraction, as with agonist-induced contraction at experimentally
      fixed Ca2+ concentrations, involves (a) G protein activation, (b) regulated
      inhibition of MLC phosphatase, and (c) MLC20 phosphorylation via a Ca2+
      independent MLCK. The pathways that lead to inhibition of MLC phosphatase by
      G(q/13)-coupled receptors are initiated by sequential activation of
      Galpha(q)/alpha13, RhoGEF, and RhoA, and involve Rho kinase-mediated
      phosphorylation of the regulatory subunit of MLC phosphatase (MYPT1) and/or PKC
      mediated phosphorylation of CPI-17, an endogenous inhibitor of MLC phosphatase.
      Sustained MLC20 phosphorylation is probably induced by the Ca2+-independent MLCK,
      ZIP kinase. The pathways initiated by G(i)-coupled receptors involve sequential
      activation of Gbetagamma(i), PI 3-kinase, and the Ca2+-independent MLCK, integrin
      linked kinase. The last phosphorylates MLC20 directly and inhibits MLC
      phosphatase by phosphorylating CPI-17. PKA and PKG, which mediate relaxation, act
      upstream to desensitize the receptors (VPAC2 and NPR-C), inhibit adenylyl and
      guanylyl cyclase activities, and stimulate cAMP-specific PDE3 and PDE4 and cGMP
      specific PDE5 activities. These kinases also act downstream to inhibit (a)
      initial contraction by inhibiting Ca2+ mobilization and (b) sustained contraction
      by inhibiting RhoA and targets downstream of RhoA. This increases MLC phosphatase
      activity and induces MLC20 dephosphorylation and muscle relaxation.

PMID- 16460277
TI  - CNG and HCN channels: two peas, one pod.
AB  - Cyclic nucleotide-activated ion channels play a fundamental role in a variety of
      physiological processes. By opening in response to intracellular cyclic
      nucleotides, they translate changes in concentrations of signaling molecules to
      changes in membrane potential. These channels belong to two families: the cyclic
      nucleotide-gated (CNG) channels and the hyperpolarization-activated cyclic
      nucleotide-modulated (HCN) channels. The two families exhibit high sequence
      similarity and belong to the superfamily of voltage-gated potassium channels.
      Whereas HCN channels are activated by voltage and CNG channels are virtually
      voltage independent, both channels are activated by cyclic nucleotide binding.
      Furthermore, the channels are thought to have similar channel structures, leading
      to similar mechanisms of activation by cyclic nucleotides. However, although
      these channels are structurally and behaviorally similar, they have evolved to
      perform distinct physiological functions. This review describes the physiological
      roles and biophysical behavior of CNG and HCN channels. We focus on how
      similarities in structure and activation mechanisms result in common biophysical
      models, allowing CNG and HCN channels to be viewed as a single genre.

PMID- 16460274
TI  - Brainstem circuits regulating gastric function.
AB  - Brainstem parasympathetic circuits that modulate digestive functions of the
      stomach are comprised of afferent vagal fibers, neurons of the nucleus tractus
      solitarius (NTS), and the efferent fibers originating in the dorsal motor nucleus
      of the vagus (DMV). A large body of evidence has shown that neuronal
      communications between the NTS and the DMV are plastic and are regulated by the
      presence of a variety of neurotransmitters and circulating hormones as well as
      the presence, or absence, of afferent input to the NTS. These data suggest that
      descending central nervous system inputs as well as hormonal and afferent
      feedback resulting from the digestive process can powerfully regulate vago-vagal
      reflex sensitivity. This paper first reviews the essential "static" organization
      and function of vago-vagal gastric control neurocircuitry. We then present data
      on the opioidergic modulation of NTS connections with the DMV as an example of
      the "gating" of these reflexes, i.e., how neurotransmitters, hormones, and vagal
      afferent traffic can make an otherwise static autonomic reflex highly plastic.

PMID- 16460278
TI  - Claudins and epithelial paracellular transport.
AB  - Tight junctions form continuous intercellular contacts controlling solute
      movement through the paracellular pathway across epithelia. Paracellular barriers
      vary among epithelia in electrical resistance and behave as if they are lined
      with pores that have charge and size selectivity. Recent evidence shows that
      claudins, a large family (at least 24 members) of intercellular adhesion
      molecules, form the seal and its variable pore-like properties. This evidence
      comes from the study of claudins expressed in cultured epithelial cell models,
      genetically altered mice, and human mutants. We review information on the
      structure, function, and transcriptional and posttranslational regulation of the
      claudin family as well as of their evolutionarily distant relatives called the
      PMP22/EMP/MP20/claudin, or pfam00822, superfamily.

PMID- 16460279
TI  - Role of FXYD proteins in ion transport.
AB  - The FXYD proteins are a family of seven homologous single transmembrane segment
      proteins (FXYD1-7), expressed in a tissue-specific fashion. The FXYD proteins
      modulate the function of Na,K-ATPase, thus adapting kinetic properties of active
      Na+ and K+ transport to the specific needs of different cells. Six FXYD proteins
      are known to interact with Na,K-ATPase and affect its kinetic properties in
      specific ways. Although effects of FXYD proteins on parameters such as K(1/2)Na+,
      K(1/2)K+, K(m)ATP, and V(max) are modest, usually twofold, these effects may have
      important long-term consequences for homeostasis of cation balance. In this
      review we summarize basic features of FXYD proteins and present recent evidence
      for functional effects, structure-function relations and structural interactions
      with Na,K-ATPase. We then discuss possible physiological roles, based on in vitro
      observations and newly available knockout mice models. Finally, we also consider
      evidence that FXYD proteins affect functioning of other ion transport systems.

PMID- 16460280
TI  - Sgk kinases and their role in epithelial transport.
AB  - The serum/glucocorticoid-induced kinase Sgk1 plays an important role in the
      regulation of epithelial ion transport. This kinase is very rapidly regulated at
      the transcriptional level as well as via posttranslational modifications
      involving phosphorylation by the MAP or PI-3 kinase pathways and/or
      ubiquitylation. Although Sgk1 is a cell survival kinase, its primary role likely
      concerns the regulation of epithelial ion transport, as suggested by the
      phenotype of Sgk1-null mice, which display a defect in Na( homeostasis owing to
      disturbed renal tubular Na+ handling. In this review we first discuss the
      molecular, cellular, and regulatory aspects of Sgk1 and its paralogs. We then
      discuss its roles in the physiology and pathophysiology of epithelial ion
      transport.

PMID- 16460281
TI  - The association of NHERF adaptor proteins with g protein-coupled receptors and
      receptor tyrosine kinases.
AB  - The sodium-hydrogen exchanger regulatory factors (NHERF-1 and NHERF-2) are a
      family of adaptor proteins characterized by the presence of two tandem PDZ
      protein interaction domains and a C-terminal domain that binds the cytoskeleton
      proteins ezrin, radixin, moesin, and merlin. The NHERF proteins are highly
      expressed in the kidney, small intestine, and other organs, where they associate
      with a number of transporters and ion channels, signaling proteins, and
      transcription factors. Recent evidence has revealed important associations
      between the NHERF proteins and several G protein-coupled receptors such as the
      beta2-adrenergic receptor, the kappa-opioid receptor, and the parathyroid hormone
      receptor, as well as growth factor tyrosine kinase receptors such as the platelet
      derived growth factor receptor and the epidermal growth factor receptor. This
      review summarizes the emerging data on the biochemical mechanisms, physiologic
      outcomes, and potential clinical implications of the assembly and disassembly of
      receptor/NHERF complexes.

PMID- 16460282
TI  - Stress transmission in the lung: pathways from organ to molecule.
AB  - Gas exchange, the primary function of the lung, can come about only with the
      application of physical forces on the macroscale and their transmission to the
      scale of small airway, small blood vessel, and alveolus, where they serve to
      distend and stabilize structures that would otherwise collapse. The pathway for
      force transmission then continues down to the level of cell, nucleus, and
      molecule; moreover, to lesser or greater degrees most cell types that are
      resident in the lung have the ability to generate contractile forces. At these
      smallest scales, physical forces serve to distend the cytoskeleton, drive
      cytoskeletal remodeling, expose cryptic binding domains, and ultimately modulate
      reaction rates and gene expression. Importantly, evidence has now accumulated
      suggesting that multiscale phenomena span these scales and govern integrative
      lung behavior.

PMID- 16460283
TI  - Regulation of normal and cystic fibrosis airway surface liquid volume by phasic
      shear stress.
AB  - The physical removal of viruses and bacteria on the mucociliary escalator is an
      important aspect of the mammalian lung's innate defense mechanism. The volume of
      airway surface liquid (ASL) present in the respiratory tract is a critical
      determinant of both mucus hydration and the rate of mucus clearance from the
      lung. ASL volume is maintained by the predominantly ciliated epithelium via
      coordinated regulation of (a) absorption, by the epithelial Na+ channel, and (b)
      secretion, by the Ca2+-activated Cl- channel (CaCC) and CFTR. This review
      provides an update on our current understanding of how shear stress regulates ASL
      volume height in normal and cystic fibrosis (CF) airway epithelia through
      extracellular ATP- and adenosine (ADO)-mediated pathways that modulate ion
      transport and ASL volume homeostasis. We also discuss (a) how derangement of the
      ADO-CFTR pathway renders CF airways vulnerable to viral infections that deplete
      ASL volume and produce mucus stasis, and (b) potential shear stress-dependent
      therapies for CF.

PMID- 16460284
TI  - Chronic effects of mechanical force on airways.
AB  - Airways are embedded in the mechanically dynamic environment of the lung. In
      utero, this mechanical environment is defined largely by fluid secretion into the
      developing airway lumen. Clinical, whole lung, and cellular studies demonstrate
      pivotal roles for mechanical distention in airway morphogenesis and cellular
      behavior during lung development. In the adult lung, the mechanical environment
      is defined by a dynamic balance of surface, tissue, and muscle forces. Diseases
      of the airways modulate both the mechanical stresses to which the airways are
      exposed as well as the structure and mechanical behavior of the airways. For
      instance, in asthma, activation of airway smooth muscle abruptly changes the
      airway size and stress state within the airway wall; asthma also results in
      profound remodeling of the airway wall. Data now demonstrate that airway
      epithelial cells, smooth muscle cells, and fibroblasts respond to their
      mechanical environment. A prominent role has been identified for the epithelium
      in transducing mechanical stresses, and in both the fetal and mature airways,
      epithelial cells interact with mesenchymal cells to coordinate remodeling of
      tissue architecture in response to the mechanical environment.

PMID- 16460285
TI  - The contribution of biophysical lung injury to the development of biotrauma.
AB  - Patients with severe acute respiratory distress syndrome who die usually succumb
      to multiorgan failure as opposed to hypoxia. Despite appropriate resuscitation,
      some patients' symptoms persist on a downward spiral, apparently propagated by an
      uncontained systemic inflammatory response. This phenomenon is not well
      understood. However, a novel hypothesis to explain this observation proposes that
      it is related to the life-saving ventilatory support used to treat the
      respiratory failure. According to this hypothesis, mechanical ventilation per se,
      by altering both the magnitude and the pattern of lung stretch, can cause changes
      in gene expression and/or cellular metabolism that ultimately can lead to the
      development of an overwhelming inflammatory response-even in the absence of overt
      structural damage. This mechanism of injury has been termed biotrauma. In this
      review we explore the biotrauma hypothesis, the causal relationship between
      biophysical injury and organ failure, and its implications for the future therapy
      and management of critically ill patients.

PMID- 16460286
TI  - An introduction to TRP channels.
AB  - The aim of this review is to provide a basic framework for understanding the
      function of mammalian transient receptor potential (TRP) channels, particularly
      as they have been elucidated in heterologous expression systems. Mammalian TRP
      channel proteins form six-transmembrane (6-TM) cation-permeable channels that may
      be grouped into six subfamilies on the basis of amino acid sequence homology
      (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Selected functional properties of TRP
      channels from each subfamily are summarized in this review. Although a single
      defining characteristic of TRP channel function has not yet emerged, TRP channels
      may be generally described as calcium-permeable cation channels with polymodal
      activation properties. By integrating multiple concomitant stimuli and coupling
      their activity to downstream cellular signal amplification via calcium permeation
      and membrane depolarization, TRP channels appear well adapted to function in
      cellular sensation. Our review of recent literature implicating TRP channels in
      neuronal growth cone steering suggests that TRPs may function more widely in
      cellular guidance and chemotaxis. The TRP channel gene family and its
      nomenclature, the encoded proteins and alternatively spliced variants, and the
      rapidly expanding pharmacology of TRP channels are summarized in online
      supplemental material.

PMID- 16460288
TI  - Permeation and selectivity of TRP channels.
AB  - Ion channels are pore-forming transmembrane proteins that allow ions to permeate
      biological membranes. Pore structure plays a crucial role in determining the ion
      permeation and selectivity properties of particular channels. In the past few
      decades, efforts have been undertaken to identify key elements of the pore
      regions of different classes of ion channels. In this review, we summarize
      current knowledge about permeation and selectivity of channel proteins from the
      transient receptor potential (TRP) superfamily. Whereas all TRP channels are
      permeable for cations, only two TRP channels are impermeable for Ca2+ (TRPM4,
      TRPM5), and two others are highly Ca2+ permeable (TRPV5, TRPV6). Despite the
      great advances in the TRP channel field during the past decade, only a limited
      number of reports have dealt with functional characterization of pore properties,
      biophysical aspects of cation permeation, or description of pore structures of
      TRP channels. This review gives an overview of available experimental and
      theoretical data and discusses the functional impact of pore-structure
      modifications on TRP channel properties.

PMID- 16460289
TI  - TRP channels in C. elegans.
AB  - The TRP (transient receptor potential) superfamily of cation channels is present
      in all eukaryotes, from yeast to mammals. Many TRP channels have been studied in
      the nematode Caenorhabditis elegans, revealing novel biological functions,
      regulatory modes, and mechanisms of localization. C. elegans TRPV channels
      function in olfaction, mechanosensation, osmosensation, and activity-dependent
      gene regulation. Their activity is regulated by G protein signaling and
      polyunsaturated fatty acids. C. elegans TRPPs related to human polycystic kidney
      disease genes are expressed in male-specific neurons. The KLP-6 kinesin directs
      TRPP channels to cilia, where they may interact with F0/F1 ATPases. A sperm
      specific TRPC channel, TRP-3, is required for fertilization. Upon sperm
      activation, TRP-3 translocates from an intracellular compartment to the plasma
      membrane to allow store-operated Ca2+ entry. The TRPM channels GON-2 and GTL-2
      regulate Mg2+ homeostasis and Mg2+ uptake by intestinal cells; GON-2 is also
      required for gonad development. The TRPML CUP-5 promotes normal lysosome
      biogenesis and prevents apoptosis. Dynamic, precise expression of TRP proteins
      generates a remarkable range of cellular functions.

PMID- 16460290
TI  - Debating health workforce innovation.
AB  - The profession should speak with one voice in the debate about task transfer.

PMID- 16460291
TI  - Acute pain management: the evidence grows.
AB  - An Australian document now has an important role in acute pain management
      worldwide.

PMID- 16460287
TI  - Insights on TRP channels from in vivo studies in Drosophila.
AB  - Transient receptor potential (TRP) channels mediate responses in a large variety
      of signaling mechanisms. Most studies on mammalian TRP channels rely on
      heterologous expression, but their relevance to in vivo tissues is not entirely
      clear. In contrast, Drosophila TRP and TRP-like (TRPL) channels allow direct
      analyses of in vivo function. In Drosophila photoreceptors, activation of TRP and
      TRPL is mediated via the phosphoinositide cascade, with both Ca2+ and
      diacylglycerol (DAG) essential for generating the light response. In tissue
      culture cells, TRPL channels are constitutively active, and lipid second
      messengers greatly facilitate this activity. Inhibition of phospholipase C (PLC)
      completely blocks lipid activation of TRPL, suggesting that lipid activation is
      mediated via PLC. In vivo studies in mutant Drosophila also reveal an acute
      requirement for lipid-producing enzyme, which may regulate PLC activity. Thus,
      PLC and its downstream second messengers, Ca2+ and DAG, constitute critical
      mediators of TRP/TRPL gating in vivo.

PMID- 16460292
TI  - Australia's role in promoting achievement of the Millennium Development Goals.

PMID- 16460293
TI  - Health workforce innovation conference.

PMID- 16460294
TI  - Zinc and vitamin A supplementation in Indigenous Australian children hospitalised
      with lower respiratory tract infection: a randomised controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of supplementation with zinc and vitamin A in
      Indigenous children hospitalised with acute lower respiratory infection (ALRI).
      DESIGN: Randomised controlled, 2-by-2 factorial trial of supplementation with
      zinc and vitamin A. SETTING AND PARTICIPANTS: 187 Indigenous children aged < 11
      years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001
      to July 2002). INTERVENTIONS: Vitamin A was administered on Days 1 and 5 of
      admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and
      zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants
      under 12 months) or 40 mg. MAIN OUTCOME MEASURE: Time to clinical recovery from
      fever and tachypnoea, duration of hospitalisation, and readmission for ALRI
      within 120 days. RESULTS: There was no clinical benefit of supplementation with
      vitamin A, zinc or the two combined, with no significant difference between zinc
      and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in
      time to resolution of fever or tachypnoea, or duration of hospitalisation.
      Instead, we found increased morbidity; children given zinc had increased risk of
      readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003-6.1).
      CONCLUSION: This study does not support the use of vitamin A or zinc
      supplementation in the management of ALRI requiring hospitalisation in Indigenous
      children living in remote areas. Even in populations with high rates of ALRI and
      poor living conditions, vitamin A and zinc therapy may not be useful. The effect
      of supplementation may depend on the prevalence of deficiency of these
      micronutrients in the population.

PMID- 16460295
TI  - Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non
      randomised trial comparing percutaneous vertebroplasty with conservative therapy.
AB  - OBJECTIVE: To assess the safety and efficacy of percutaneous vertebroplasty for
      the treatment of acute osteoporotic vertebral fractures. DESIGN: A prospective,
      non-randomised, "intention-to-treat" 2-year study. PATIENTS AND SETTING: 126
      consecutive patients (39 men and 87 women, aged 51-95 years) with acute
      osteoporotic vertebral fractures presenting to St George Hospital from November
      2000 to December 2002. They comprised 88 patients treated by percutaneous
      vertebroplasty and 38 by conservative therapy. MAIN OUTCOME MEASURES: Primary
      outcomes--changes in patients' pain score and level of function recorded at 24
      hours, 6 weeks, 6-12 months and 24 months after therapy. Secondary outcomes-
      occurrence of new clinical or radiological vertebral fractures and survival at 2
      years. RESULTS: Three minor complications (fractured pedicle and psoas muscle
      haemorrhage) occurred in the vertebroplasty group during the first year of the
      study. Outcomes in vertebroplasty-treated patients (60% reduction in visual
      analogue pain scores from 20 to 8; P < 0.001), a rapid return to normal function
      (29% improvement in physical functioning from 14 to 18; P < 0.001) and lower
      rates of hospitalisation (43% reduction in the mean number of hospital bed-days
      occupied) were better than those treated conservatively (P < 0.001 for the
      comparison of all variables at 24 hours). Lower pain scores persisted in the
      vertebroplasty-treated group at 6 weeks (P < 0.001), but no differences between
      the two groups were evident at 12 and 24 months. In the vertebroplasty-treated
      group compared with the control group, the rates of new vertebral fractures
      (clinically and by radiographic assessment) (hazard ratio, 1.13; 95% CI, 0.52
      2.46; P = 0.76) and death (hazard ratio, 1.07; 95% CI, 0.42-2.76; P = 0.89)
      showed no significant difference. CONCLUSION: The analgesic benefit of
      percutaneous vertebroplasty and the low complication rates suggest that it is a
      useful therapy for acute painful osteoporotic vertebral fractures.

PMID- 16460296
TI  - Invasive pneumococcal disease in Indigenous people in north Queensland, 1999
      2004.
AB  - OBJECTIVE: To describe the epidemiology of invasive pneumococcal disease (IPD),
      and the impact of pneumococcal vaccines on IPD, in Indigenous people in north
      Queensland. SETTING: North Queensland, 1999-2004; there are about 53 750
      Indigenous people in the region, including nearly 6900 children < 5 years and
      nearly 5650 adults > or = 50 years. MAIN OUTCOME MEASURES: Incidences of IPD in
      Indigenous children and in Indigenous adults compared between the 3 years before
      and after the introduction of a 7-valent pneumococcal conjugate vaccine (7vPCV)
      (1999-2001 versus 2002-2004). RESULTS: Estimated annual incidence of IPD in
      Indigenous children < 5 years of age declined from 170 to 78 cases per 100 000 in
      the 3 years following the introduction of 7vPCV in 2001. The annual incidence of
      vaccine-preventable IPD in Indigenous adults had declined by 86% since a 23
      valent pneumococcal polysaccharide vaccine (23vPPV) was introduced to the region
      in 1996, to 15 cases per 100 000 (95% CI, 8-25) in 2002-2004. CONCLUSION:
      Although there was a rapid decline in IPD in young Indigenous children, it is
      unlikely that the incidence will fall much further with the current 7-valent
      vaccine. There was a suggestion that vaccinating Indigenous children indirectly
      protected those aged 5-14 years and Indigenous adults > or =15 years of age.
      Incidence of IPD in Indigenous adults in 2002-2004 was the lowest on record in
      the region.

PMID- 16460297
TI  - Early combination disease modifying antirheumatic drug treatment for rheumatoid
      arthritis.
AB  - Most people presenting with rheumatoid arthritis today can expect to achieve
      disease suppression, can avoid or substantially delay joint damage and
      deformities, and can maintain a good quality of life. Optimal management requires
      early diagnosis and treatment, usually with combinations of conventional disease
      modifying antirheumatic drugs (DMARDs). If these do not effect remission,
      biological DMARDs may be beneficial. Lack of recognition of the early signs of
      rheumatoid arthritis, ignorance of the benefits of early application of modern
      treatment regimens, and avoidable delays in securing specialist appointments may
      hinder achievement of best outcomes for many patients. Triage for recognising
      possible early rheumatoid arthritis must begin in primary care settings with the
      following pattern of presentation as a guide: involvement of three or more
      joints; early-morning joint stiffness of greater than 30 minutes; or bilateral
      squeeze tenderness at metacarpophalangeal or metatarsophalangeal joints.

PMID- 16460298
TI  - The Inquiry into the Waterfall train crash: implications for medical examinations
      of safety-critical workers.
AB  - The implications arising from the Inquiry into the Waterfall train crash for
      medical examinations of safety-critical workers are discussed. Examinations need
      to be appropriate for the level of risk in the job and apply current medical
      thinking. A careful balance is required between the various legal obligations,
      including duty of care, disability discrimination and privacy. The frequency of
      examinations depends on a combination of medical, economic and logistical
      factors. Health professionals who conduct examinations should be familiar with
      the occupation of the person being examined. Ethical relationships with the
      worker's general practitioner or specialist(s) must be observed. The procedures
      associated with the examinations are as important in achieving safety as the
      actual examinations. These include complying with relevant standards; providing
      all relevant documentation with a referral for an examination; acting on the
      doctor's report appropriately; and auditing the process.

PMID- 16460299
TI  - Unilateral limb hypertrophy and shoulder weakness in a 37-year-old woman.

PMID- 16460300
TI  - 4. The use and misuse of performance-enhancing substances in sport.
AB  - Doctors need to know if a patient is an athlete subject to drug testing, and to
      be aware of the legal situation surrounding drugs they prescribe such patients.
      Antidoping laws generally exist in order to provide a safe and fair environment
      for participation in sport. These laws should prevent and protect athletes from
      subjecting themselves to health risks through the use of unsafe, but performance
      enhancing drugs. Because of difficulties in proving intent to cheat, the World
      Anti-Doping Agency enforces a principle of strict liability for positive test
      results for banned substances. An area of major controversy with respect to
      liability is the "sports supplement" industry, which is poorly regulated when
      compared with prescription drugs yet is a potential source of doping violations.
      Medical practitioners can be found guilty of anti-doping violations if they
      traffic banned drugs, prescribe these to athletes or otherwise assist athletes in
      taking banned substances. Medical practitioners are also now required to complete
      paperwork (therapeutic use exemption forms) to enable athletes to take banned
      substances which are required on medical grounds for specific illnesses.

PMID- 16460301
TI  - A tender lump in the neck.

PMID- 16460302
TI  - "GP Psych Opinion": evaluation of a psychiatric consultation service.

PMID- 16460303
TI  - Mifepristone (RU-486) and limits to abortion.

PMID- 16460304
TI  - The price of health care for Medicare-ineligible asylum seekers in the community.

PMID- 16460305
TI  - Clinicians prescribing exercise: is air pollution a hazard?

PMID- 16460306
TI  - Hospital in the home: what next?

PMID- 16460307
TI  - Safety of hospital in the home.

PMID- 16460309
TI  - Activation of the superoxide-producing phagocyte NADPH oxidase requires co
      operation between the tandem SH3 domains of p47phox in recognition of a
      polyproline type II helix and an adjacent alpha-helix of p22phox.
AB  - Activation of the superoxide-producing phagocyte NADPH oxidase, crucial for host
      defence, requires an SH3 (Src homology 3)-domain-mediated interaction of the
      regulatory protein p47phox with p22phox, a subunit of the oxidase catalytic core
      flavocytochrome b558. Although previous analysis of a crystal structure has
      demonstrated that the tandem SH3 domains of p47phox sandwich a short PRR (proline
      rich region) of p22phox (amino acids 151-160), containing a polyproline II helix,
      it has remained unknown whether this model is indeed functional in activation of
      the oxidase. In the present paper we show that the co-operativity between the two
      SH3 domains of p47phox, as expected from the model, is required for oxidase
      activation. Deletion of the linker between the p47phox SH3 domains results not
      only in a defective binding to p22phox but also in a loss of the activity to
      support superoxide production. The present analysis using alanine-scanning
      mutagenesis identifies Pro152, Pro156 and Arg158 in the p22phox PRR as residues
      indispensable for the interaction with p47phox. Pro152 and Pro156 are recognized
      by the N-terminal SH3 domain, whereas Arg158 contacts with the C-terminal SH3
      domain. Amino acid substitution for any of the three residues in the p22phox PRR
      abrogates the superoxide-producing activity of the oxidase reconstituted in
      intact cells. The bis-SH3-mediated interaction of p47phox with p22phox thus
      functions to activate the phagocyte oxidase. Furthermore, we provide evidence
      that a region C-terminal to the PRR of p22phox (amino acids 161-164), adopting an
      a-helical conformation, participates in full activation of the phagocyte oxidase
      by fortifying the association with the p47phox SH3 domains.

PMID- 16460310
TI  - Simplified modelling of metabolic pathways for flux prediction and optimization:
      lessons from an in vitro reconstruction of the upper part of glycolysis.
AB  - Explicit modelling of metabolic networks relies on well-known mathematical tools
      and specialized computer programs. However, identifying and estimating the values
      of the very numerous enzyme parameters inherent to the models remain a tedious
      and difficult task, and the rate equations of the reactions are usually not known
      in sufficient detail. A way to circumvent this problem is to use 'non
      mechanistic' models, which may account for the behaviour of the systems with a
      limited number of parameters. Working on the first part of glycolysis
      reconstituted in vitro, we showed how to derive, from titration experiments,
      values of effective enzyme activity parameters that do not include explicitly any
      of the classical kinetic constants. With a maximum of only two parameters per
      enzyme, this approach produced very good estimates for the flux values, and
      enabled us to determine the optimization conditions of the system, i.e. to
      calculate the set of enzyme concentrations that maximizes the flux. This fast and
      easy method should be valuable in the context of integrative biology or for
      metabolic engineering, where the challenge is to deal with the dramatic increase
      in the number of parameters when the systems become complex.

PMID- 16460311
TI  - Mapping and conformational characterization of the DNA-binding region of the
      breast cancer susceptibility protein BRCA1.
AB  - The breast cancer susceptibility gene, BRCA1, encodes a large nuclear
      phosphoprotein, the major isoform of which is 1863 amino acids in size. Structure
      function studies have been largely restricted to the only two domains identified
      by homology searches: the RING (really interesting new gene) and BRCT (BRCA1 C
      terminus) domains. However, we have recently reported the identification of a
      large central soluble region of BRCA1 (residues 230-534) that binds specifically
      to four-way junction DNA, a property that potentially facilitates its role in the
      repair of DNA lesions by homologous recombination. We have now used a combination
      of limited proteolysis and extension cloning to identify more accurately the DNA
      binding region of BRCA1. Limited trypsinolysis of BRCA1-(230-534) resulted in the
      production of a soluble domain identified as residues 230-339. However, after
      cloning, expression and purification of this region, studies revealed that it was
      unable to bind to four-way junctions, suggesting that the DNA-binding activity,
      in part, resides within residues 340-534. A series of fragments extending from
      residue 340 were produced, and each was tested for its ability to bind to four
      way junction DNA in gel retardation assays. In these experiments, residues 340
      554 of BRCA1 were identified as the minimal DNA-binding region. We then went on
      to characterize the conformation of this region using CD spectroscopy and
      analytical centrifugation.

PMID- 16460312
TI  - Spectral optical coherence tomography: a new imaging technique in contact lens
      practice.
AB  - PURPOSE: Spectral optical coherence tomography (SOCT) is a new non-invasive, non
      contact, high-resolution technique, which provides cross-sectional images of
      objects that weakly absorb and scatter light. The aim of this article is to
      demonstrate the application of SOCT to imaging of eyes fitted with contact
      lenses. METHODS: Nine eyes of six different subjects fitted with various contact
      lenses have been examined with a slit-lamp and a prototype SOCT instrument.
      RESULTS: Our SOCT system provides high-resolution (4-6 mum longitudinal, 10 mum
      transversal) tomograms composed of 3000-5000 A-scans with acquisition time of 100
      250 ms. The quality of the images is adequate for detailed evaluation of contact
      lens fit. Design, shape and lens edge position were assessed, and complications
      of contact lens wear could be visualized. Thickness of the lens, corneal
      epithelium and stroma as well as the space between the lens and the eye surface
      have been measured. CONCLUSIONS: SOCT allows high-resolution, cross-sectional
      visualization of the eye fitted with a contact lens. The ability to carry out a
      detailed evaluation of the fitting relationship between the lens and the ocular
      surface might be useful in research and optometric practice. SOCT can also be
      helpful in diagnosis, evaluation and documentation of contact lens complications.

PMID- 16460313
TI  - Infectious keratitis related to orthokeratology.
AB  - PURPOSE: To report 28 cases of infectious keratitis related to orthokeratology
      lens overnight wear in China. METHODS: From March 2000 to August 2001, 28 cases
      of infectious keratitis related to overnight orthokeratology lens wear were
      diagnosed in Beijing Institute of Ophthalmology. These were retrospectively
      reviewed with regard to the pathogens isolated, duration of wear, the time since
      onset of symptoms, and age. Cultures of corneal scrapes for bacteria, fungus and
      Acanthamoeba were performed in all of the 28 cases. RESULTS: All cases were
      students, including 10 males and 18 females, average age was 16 years (range 10
      21 years). The duration of orthokeratology overnight wearing was from 2 weeks to
      2 years. Uncorrected visual acuity (UCVA) on initial examination in our institute
      was from 20/200 to light perception. Of 28 isolates, 24 were culture positive
      (including 11 bacteria, 11 Acanthamoeba and two fungi), and four were culture
      negative. In two of the four culture negative cases, Acanthamoeba cysts were
      detected in the corneal stroma with the confocal microscope. Acanthamoeba and
      Pseudomonas aeruginosa accounted for 75% (21 of 28) of the cases of infectious
      keratitis. CONCLUSION: Infectious keratitis is a severe complication associated
      with overnight orthokeratology lens wear. Ophthalmologists should pay more
      attention to this complication in practice.

PMID- 16460315
TI  - Accommodation and the relationship to subjective symptoms with near work for
      young school children.
AB  - The aim of this work was to study the relation between subjective symptoms at
      near and ocular accommodation in terms of the amplitude of accommodation and the
      relative accommodation. A secondary aim was to discuss the diagnosis of
      accommodative insufficiency. The chosen cohort was examined on two occasions with
      1.8 years in between. The first examination included 72 children, 43 boys (mean
      age 8.1 years, ranging from 5.8 to 9.8) and 29 girls (mean age 8.3 years, ranging
      from 6.2 to 10.0). The second examination included 59 of these children, 34 boys
      (mean age 9.9 years, ranging from 7.8 to 11.7) and 25 girls (mean age 10.1
      ranging from 8.0 to 11.8). Subjective symptoms at near work (headache,
      asthenopia, floating text, facility problems) were recorded and the amplitude and
      the relative accommodation, both positive and negative, were measured. The result
      from the questionnaire showed that at the first examination more than one-third
      of the children (34.7%) reported at least one subjective symptom when doing near
      work and 42.4% at the second examination. No symptoms were found among children
      younger than 7.5 years, but for children between 7.5 and 10 years old at the
      first examination, the prevalence of at least one symptom was 47.2%. At the
      second examination, symptoms were reported also for the youngest children, i.e.
      from the age of 8 years. The discrimination ability for the amplitude of
      accommodation, both monocular and binocular, was significant. In the first
      examination the difference between the mean for the two groups (i.e. with and
      without at least one symptom) was around 2.00 D monocular and 3.00 D binocular.
      Corresponding figures from the second examination was a difference between the
      mean for the two groups of around 3.50 D monocular and nearly 4.00 D binocular.
      We suggest that accommodation measurements should be performed more routinely and
      regularly, maybe as screening, especially in children over 8 years of age.

PMID- 16460314
TI  - The effects of supplementation with lutein and/or zeaxanthin on human macular
      pigment density and colour vision.
AB  - BACKGROUND: Both yellow-blue (YB) discrimination thresholds and macular pigment
      optical density (MPOD) measurements in the eye exhibit large variability in the
      normal population. Although it is well established that selective absorption of
      blue light by the macular pigment (MP) can significantly affect trichromatic
      colour matches, the extent to which the MP affects colour discrimination (CD)
      sensitivity remains controversial. OBJECTIVE: In this study, we assess whether
      the variability in YB thresholds is attributable to differences in MPOD, both at
      the fovea and in the paracentral visual field. We also investigated whether
      higher levels of MP offer any advantage in other visual functions such as red
      green (RG) CD sensitivity. DESIGN: CD thresholds and spatial MPOD profiles were
      measured in 24 normal trichromats supplemented with zeaxanthin (OPTISHARP) and/or
      lutein. Novel stimulus conditions that isolate YB and RG chromatic mechanisms
      were employed and MPOD profiles were measured up to an eccentricity of 8 degrees.
      RESULTS: The data reveal an increase in MPOD in the supplemented subjects that
      was almost uniform within a centre region around the fovea subtending +/-4
      degrees. RG sensitivity was high in all subjects with thresholds well within the
      normal range. Unexpectedly, YB thresholds were also normal and showed no
      correlation with MPOD. A model for threshold CD based on appropriate combinations
      of cone contrast signals was developed to explain the experimental findings.
      CONCLUSIONS: YB thresholds remain unaffected by supplementation with lutein
      and/or zeaxanthin rather, at increased MPOD levels, RG vision tends to be
      improved. The model accounts for the absence of correlation between MPOD and YB
      thresholds and predicts a marginal improvement in RG discrimination when MPOD is
      high.

PMID- 16460316
TI  - Computer-based measurement of letter and word acuity.
AB  - Determining causes of poor reading ability is an important step in trying to
      ameliorate reading performance in low-vision patients. One important parameter is
      word acuity. The principal aim of the current study is to develop a method to
      reliably measure acuities for isolated lowercase letters and words of differing
      length that can be used to test low-vision patients. Using isolated stimuli means
      that testing is relatively free of potential crowding and/or distracting
      attentional effects from surrounding words, it is unambiguous which stimulus
      subjects are trying to read and response times can be recorded for each stimulus.
      Across a series of experiments, subjects with normal vision were asked to read
      isolated lowercase single letters and lowercase words of 4, 7 and 10 letters, in
      separate tests. Acuities for uppercase Sloan letters were also measured to
      provide a reference, as they are commonly used to measure visual acuity. Each
      test was based upon the design principles and scoring procedures used in the
      Bailey-Lovie and ETDRS charts. Acuities for uppercase Sloan letters were found to
      be equivalent whether measured using ETDRS charts or the computer-based method.
      Measurement of acuities for lowercase single letters and lowercase words of 4, 7
      and 10 letters had a reliability that was no worse than acuities for uppercase
      Sloan letters. Lowercase word acuities were essentially independent of word
      length. Acuities for single lowercase letters and lowercase words were slightly
      better than uppercase Sloan letters acuity. Optimal processing of lowercase
      single letters and 4-, 7- and 10-letter words occurred at character sizes that
      were at least 0.2-0.40 log MAR above acuity threshold, i.e. between 1.5 and 3
      times threshold acuity for that particular stimulus. In general, critical
      character sizes appear similar across word lengths as progressive increases or
      decreases in these values were not observed as a function of the number of
      letters in the stimulus. We conclude that a computer-based method of stimulus
      presentation can be used to obtain highly repeatable measures of acuity for
      lowercase single letters and lowercase words in normal vision.

PMID- 16460317
TI  - Effects of task lighting on visual function in age-related macular degeneration.
AB  - The purpose was to investigate the effects of the spectral power distribution
      (SPD) and illuminance of task lighting on visual function in age-related macular
      degeneration (ARMD) compared to normal healthy eyes. Twenty-eight subjects with
      ARMD and 18 age-matched normal subjects were studied. The effects on visual
      function were determined for four common task light sources: standard pearl coat
      incandescent (SP), daylight blue incandescent (DL), warm white fluorescent (WW)
      and cool white fluorescent (CW). Apart from a small, statistically significant
      improvement in contrast sensitivity with DL compared to SP lighting (0.5 dB, p =
      0.01), there were no significant effects of SPD on other visual functions and no
      differences in the effects for subjects with ARMD and those with normal vision.
      Thus, for task lighting typically used in low vision rehabilitation, the SPD
      would seem to be of minimal clinical importance to visual function. However,
      increasing the task illuminance had a greater effect on visual function, in
      particular for subjects with ARMD (p < 0.01). For an increase in illuminance from
      300 to 3000 lux, the mean increase in contrast sensitivity and near visual acuity
      was 1.5 dB and 0.13 log MAR, respectively. Although this effect is not large, we
      suggest that it is clinically relevant and supports the provision of additional
      task illuminance as an important part of low vision rehabilitation for patients
      with ARMD.

PMID- 16460318
TI  - Ray tracing through a schematic eye containing second-order (quadric) surfaces
      using 4 x 4 matrix notation.
AB  - Ray tracing is used in ophthalmology for evaluation of the optical properties of
      the eye. We demonstrate an algebraic method for tracing a bundle of rays through
      the optical system of an eye containing aspheric surfaces. Restricting to second
      order surfaces (quadric surfaces) such as ellipsoids, paraboloids or
      hyperboloids, a surface is described by a 4 x 4 matrix. In this case, the normal
      vector can be derived analytically and the ray-surface intersection is calculated
      by solving a quadratic equation. We applied this straightforward matrix-based
      strategy to the spherical 4-surface Le Grand schematic eye, and the Le Grand eye
      modified by Kooijman containing four aspheric surfaces. We calculated the spot
      diagram for the focal plane as well as a pre- and post-focal plane for both model
      eyes, and found that the optical quality of the aspheric model characterized by
      the ray scatter in the spot diagram at the focal plane is much better than that
      of the spherical model. This calculation strategy may be helpful for evaluating
      the image distortion of decentred or tilted spherical or aspheric artificial
      intra-ocular lenses.

PMID- 16460319
TI  - The power of a cylinder in an oblique meridian: revisiting an old controversy.
AB  - The sine-squared correlation states that the cylinder power in an oblique
      meridian forming an angle beta with the axis of the cylinder is reduced to
      sin(2)beta of the maximal power. The sine-squared relationship is fundamental in
      paraxial optics, but its validity has repeatedly been questioned during the last
      century. It appears that two powers are operative in an oblique meridian,
      curvital and torsional. Curvital power is responsible for refraction in the plane
      of the meridian, while the torsional component twists the light out of that
      plane. Curvital power is the traditional power concept, while torsional power has
      only recently been described. The long-standing criticism of the sine-squared
      correlation is based on the erroneous assumption that only curvital power is
      operational in paraxial imagery. Curvital and torsional power are both derived
      from the sine-squared correlation. The concept of these dual powers repudiates
      the criticism and is in complete accordance with paraxial optics.

PMID- 16460320
TI  - Improvements in performance following optometric vision therapy in a child with
      dyspraxia.
AB  - SS, an 8-year-old boy with dyspraxia, presented for behavioural optometry
      assessment. He had been diagnosed with a subtle form of dyspraxia by his
      paediatric occupational therapist, based on poor proprioception, delayed
      bilateral integration and poor visual perception. A full visual assessment was
      carried out. SS was given a programme of reflex inhibition exercises for 3
      months. Then, a programme of optometric vision therapy (OVT) exercises was
      prescribed at home and in practice for a period of 8 months. SS was assessed
      using a battery of occupational therapy Sensory Integration and Praxis Tests
      (SIPT) before optometric intervention, and after OVT. There were significant
      improvements in fusional reserves, accommodative facility and oculomotor control
      of pursuit and saccadic eye movements. His reading level had changed by 4 years
      in 11 months. The SIPT results showed improvements in the visual and motor/visual
      perception subtests, confirming the significant changes in visual perceptual
      performance. Consideration is given to treatment modalities for dyspraxia, and
      the studies confirming their effectivity of approach. This case study provides
      evidence supporting the use of OVT eye exercises in dyspraxia, ocular motility,
      accommodative dysfunction, learning difficulties and sports performance. The need
      for further research and inter-professional working is discussed.

PMID- 16460330
TI  - Comment on Harle, D.E., and Evans, B.J.W. (2005) Frequency doubling technology
      perimetry and standard automated perimetry in migraine. Ophthal. Physiol. Opt.
      25, 233-239.

PMID- 16460334
TI  - Cessation of periodontal care during pregnancy: effect on infant birthweight.
AB  - The goal of this study was to assess whether interruption of care for chronic
      periodontitis during pregnancy increased the risk of low-birthweight infants. A
      population-based case-control study was designed with 793 cases (infants < 2,500
      g) and a random sample of 3,172 controls (infants >or= 2,500 g). Generalized
      estimating equation models were used to relate periodontal treatment history to
      low birthweight risk and to common risk factors. The results indicate that
      periodontal care utilization was associated with a 2.35-fold increased odds of
      self-reported smoking during pregnancy (95% confidence interval: 1.48-3.71), a
      2.19-fold increased odds for diabetes (95% confidence interval: 1.21-3.98), a
      3.90-fold increased odds for black race (95% confidence interval: 2.31-6.61), and
      higher maternal age. After adjustment for these factors, interruption of
      periodontal care during pregnancy did not lead to an increased risk for a low
      birthweight infant when compared to women with no history of periodontal care
      (odds ratio, 0.96; 95% confidence interval, 0.60-1.52). In conclusion, women
      receiving periodontal care had genetic and environmental characteristics, such as
      smoking, diabetes and race, that were associated with an increased risk for low
      birthweight infants. Periodontal care patterns, in and of themselves, were
      unrelated to low-birthweight risk.

PMID- 16460335
TI  - Dental caries and salivary status in children with type 1 diabetes mellitus,
      related to the metabolic control of the disease.
AB  - The aim of this study was to investigate the relationship among type 1 diabetes
      mellitus, dental caries, and salivary status in children. The study comprised 68,
      10-15-yr-old diabetics, and 68, age- and gender-matched non-diabetic controls.
      Diabetics were categorized into well-to-moderately controlled (HbA1c < 9.0%) and
      poorly controlled (HbA1c >or= 9.0%) groups. Caries was recorded by assessing
      lesion activity at non-cavitated and cavity levels. Teeth were examined visually
      for the presence of dental plaque. Saliva was analyzed for unstimulated and
      stimulated flow rates, buffer effect, mutans streptococci, lactobacilli, and
      yeasts. Diabetics had fewer caries and plaque, lower salivary flow rates and
      buffer effect, and more frequent growth of yeasts than their non-diabetic
      controls. Well-to-moderately controlled diabetics had fewer decayed surfaces and
      lower counts of mutans streptococci and yeasts than poorly controlled diabetics,
      but the level of metabolic control of diabetes had no influence on salivary flow
      rates and buffer effect. High caries levels in diabetics were significantly
      associated with age, plaque score, and decreased unstimulated salivary flow rate,
      but were not associated with the level of metabolic control of diabetes. High
      caries experience in this study population could be related to plaque
      accumulation and/or to changes in saliva induced by diabetes mellitus.

PMID- 16460336
TI  - Preferences over dental restorative materials among young patients and dental
      professionals.
AB  - Knowledge of the patient's view is necessary, as patients' rights are an issue of
      increasing importance in dental practice. This study aimed to examine how
      dentists (n = 42), dental assistants (n = 65), and young dental patients (n =
      306) in Norway and Denmark valued three attributes of dental restorations,
      namely, expected longevity, the appearance, and the risk of an adverse reaction.
      According to the discrete choice method, participants were presented with several
      scenarios, describing different levels of the attributes, for comparison of two
      restorations (A and B). The differences among patients, dentists, and dental
      assistants were examined by logistic regression analyses. The likelihood of a
      dentist favoring one restoration over another was very sensitive to the
      difference in the expected longevity of the restorations, and much less to
      differences in visibility. The patients had considerable sensitivity to
      differences in visibility and much less to differences in duration. Danish
      teenagers attach less importance to visibility of the restoration and greater
      importance to the risk of an adverse reaction than Norwegian teenagers. All
      differences were statistically significant. Preferences associated with
      properties of dental restorations differ between teenage patients and dental
      professionals and this should be addressed in clinical decision-making.

PMID- 16460337
TI  - Plasminogen activators and their inhibitors in human saliva and salivary gland
      tissue.
AB  - The purpose of this study was to identify plasminogen activators (PA) and their
      specific inhibitors in human cell-free saliva and to investigate their expression
      in salivary gland tissue. Saliva samples were obtained from 34 patients visiting
      a neurological out-patient department. The activities of tissue and urokinase
      plasminogen activators (tPA and uPA, respectively), the relative inhibition of
      tPA, and the amounts of plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI
      2, respectively) in cell-free saliva were studied. The activities of tPA and uPA,
      and tPA inhibition, were measured using in-house microtiter plate assays, and PAI
      1 and PAI-2 levels were measured using commercial enzyme-linked immunosorbent
      assay (ELISA) kits. Immunohistochemistry was used to evaluate the expression of
      PAs and PAIs in the salivary gland. Tissue plasminogen activator activity was
      found in most samples, with a mean activity of 0.63 IU ml(-1). uPA was observed
      in only a few samples. PAI-1 was not detected, but PAI-2 was present in all
      samples (with a mean value of 11.1 ng ml(-1)). The mean PAI-2 level in women was
      12.4 and in men was 7.6 ng ml(-1). The activity of tPA and the relative
      inhibition of tPA seemed to be inversely associated. Tissue plasminogen
      activator, PAI-1, and PAI-2 were evident in salivary gland tissue, whereas the
      expression of uPA was low. The tPA activity in saliva suggests an active
      proteolysis. Plasminogen activator inhibitor 2 was found to be the main inhibitor
      of PAs in saliva.

PMID- 16460338
TI  - Effects of regional anesthesia with ropivacaine on arterial pressure and heart
      rate in healthy subjects.
AB  - The anesthetic, ropivacaine, has been used extensively in clinical practice, but
      few studies have evaluated this long-acting local anesthetic in dentistry. In
      this study we evaluated the effects of ropivacaine alone and ropivacaine +
      vasoconstrictor on the cardiovascular system when used as a dental anesthetic in
      volunteers. Thirty-two healthy subjects received two consecutive infiltrations of
      1.8 ml of either 0.75% ropivacaine or ropivacaine + epinephrine into the
      pterygomandibular region. Pain sensation, numbness of the lip, arterial pressure,
      heart rate, and electrocardiogram changes were monitored for 2 h. The onset of
      anesthesia was 10 min after the injection and lasted for more than 2 h, and
      numbness of the lip lasted for approximately 8 h. Ropivacaine alone did not cause
      significant changes in the cardiovascular parameters, but ropivacaine +
      epinephrine caused a transient increase in arterial pressure and heart rate 2 min
      postinjection. We conclude that ropivacaine alone injected into the
      pterygomandibular region does not affect the cardiovascular system and that the
      addition of epinephrine has no beneficial effect. This finding may be relevant to
      dentists endeavoring to find an anesthetic of minimal cardiovascular risk to
      produce regional anesthesia for long-lasting procedures without the need of a
      vasoconstrictor.

PMID- 16460339
TI  - Porcine dentin matrix protein 1: gene structure, cDNA sequence, and expression in
      teeth.
AB  - Dentin matrix protein 1 (DMP1) is an acidic non-collagenous protein that is
      necessary for the proper biomineralization of bone, cartilage, cementum, dentin,
      and enamel. Dentin matrix protein 1 is highly phosphorylated and potentially
      glycosylated, but there is no experimental data identifying which specific amino
      acids are modified. For the purpose of facilitating the characterization of DMP1
      from pig, which has the advantage of large developing teeth for obtaining protein
      in quantity and extensive structural information concerning other tooth matrix
      proteins, we characterized the porcine DMP1 cDNA and gene structure, raised anti
      peptide immunoglobulins that are specific for porcine DMP1, and detected DMP1
      protein in porcine tooth extracts and histological sections. Porcine DMP1 has 510
      amino acids, including a 16-amino acid signal peptide. The deduced molecular
      weight of the secreted, unmodified protein is 53.5 kDa. The protein has 93
      serines and 12 threonines in the appropriate context for phosphorylation, and
      four asparagines in a context suitable for glycosylation. Dentin matrix protein 1
      protein bands with apparent molecular weights between 30 and 45 kDa were observed
      in partially purified dentin extracts. In developing teeth, immunohistochemistry
      localized DMP1 in odontoblasts and the dentinal tubules of mineralized dentin and
      in ameloblasts, but not in the enamel matrix.

PMID- 16460340
TI  - Effect of interleukin-10 on gene expression of osteoclastogenic regulatory
      molecules in the rat dental follicle.
AB  - The aim of this study was to determine the effect of interleukin-10 (IL-10) on
      the gene expression of osteoclastogenic regulatory molecules in rat dental
      follicle cells. Interleukin-10 is an anti-inflammatory cytokine that inhibits
      alveolar bone resorption, but the molecular basis for this is unknown. Alveolar
      bone resorption is required for tooth eruption and the dental follicle functions
      to regulate the osteoclastogenesis needed for eruption. It does this by
      regulating its expression of receptor activator of nuclear factor-kappa B ligand
      (RANKL), colony-stimulating factor-1 (CSF-1), and osteoprotegerin (OPG). In this
      study, dental follicle cells were treated with IL-10, and the effect on gene
      expression of CSF-1, RANKL, and OPG was measured by reverse transcription
      polymerase chain reaction (RT-PCR). Interleukin-10 enhanced the expression of OPG
      and down-regulated the expression of RANKL and CSF-1. Laser capture
      microdissection was carried out to detect IL-10 gene expression in the dental
      follicle. Knockdown of the IL-10 gene expression in the follicle cells was
      accomplished using a short interfering RNA (siRNA) targeting IL-10 mRNA. In these
      knockdowns, RANKL expression was increased and OPG expression was decreased. All
      of these results suggest that IL-10 inhibits bone resorption by up-regulating OPG
      expression while down-regulating expression of RANKL and CSF-1.

PMID- 16460341
TI  - Odontoblast responses to GaAlAs laser irradiation in rat molars: an experimental
      study using heat-shock protein-25 immunohistochemistry.
AB  - Pulpal responses to gallium-aluminum-arsenide (GaAlAs) laser irradiation applied
      to the tooth remains to be elucidated. This study aimed to evaluate the effect of
      the GaAlAs laser on odontoblasts using immunohistochemistry for heat-shock
      protein (HSP)-25, which labels mature and newly differentiated odontoblasts. The
      mesial surface of the upper right first molar of 8-wk-old Wistar rats was lased
      at an output power of 0.5-1.5 W for 180 s. The animals were perfusion-fixed at
      intervals of 6 h to 30 d after irradiation. At 6 h to 7 d, the intensity of HSP
      25-immunoreactivity was found to be disturbed in the coronal odontoblast-layer in
      an energy-dependent manner. At 30 d, tertiary dentin with/without bone-like
      tissue was formed abundantly in the dental pulp. Statistical analysis revealed
      that the area occupied by the new hard tissues was significantly wider in 1.5 W
      lased specimens than in 0.5 W-lased specimens. An intense HSP-25 immunoreactivity
      was seen in the odontoblasts underlying the tertiary dentin, whereas
      immunoreactivity was weak around the bone-like tissue. It was concluded that the
      GaAlAs laser may induce the formation of tertiary dentin by influencing the
      secretory activity of odontoblasts. However, higher energies may cause
      irreversible changes to the pulp, often leading to the formation of an
      intrapulpal bone-like tissue.

PMID- 16460342
TI  - Differences between single- and dual-species biofilms of Streptococcus mutans and
      Veillonella parvula in growth, acidogenicity and susceptibility to chlorhexidine.
AB  - Streptococcus mutans, considered a primary pathogen in dental caries, thrives in
      dental plaque, which is a multispecies biofilm. Metabolic interactions between S.
      mutans and Veillonella parvula have been suggested. In this study we developed a
      biofilm model to quantify single-species (S. mutans or V. parvula) and dual
      species (S. mutans and V. parvula) biofilm formation, and we identified the
      differences between the respective biofilms in terms of growth, acid formation,
      and response to chlorhexidine. Polystyrene 96-well microtiter plates were used
      for biofilm formation. These biofilms were exposed to various chlorhexidine
      concentrations (0.025-0.4 mg ml(-1)) and treatment conditions. Growth of the
      biofilms and the effects of chlorhexidine were evaluated by viable counts.
      Viability of the two species in all biofilm types was similar ( approximately
      10(8) colony-forming units per well) after 72 h. Lactic acid accumulation of dual
      species biofilms was significantly lower at 48 and 72 h than single-species
      biofilms of S. mutans. Dual-species biofilms were less susceptible to
      chlorhexidine than single-species biofilms when a neutralization step was
      included. These results indicate that bacteria in dual-species biofilms have
      different properties from bacteria in single-species biofilms.

PMID- 16460343
TI  - Photosensitization of in vitro biofilms by toluidine blue O combined with a light
      emitting diode.
AB  - In natural ecosystems, micro-organisms grow preferentially attached to surfaces,
      forming matrix-enclosed biofilms. The aim of this study was to determine
      photodestruction levels in biofilms after subjecting them to photodynamic
      therapy. Biofilms of Streptococcus mutans, S. sobrinus, and S. sanguinis were
      grown on enamel slabs for 3, 5 or 7 d. Both the number of viable micro-organisms
      and the concentration of water-insoluble polysaccharides were analysed, and
      mineral loss (DeltaZ) analyses were performed on the enamel slabs. The
      antimicrobial potential of toluidine blue O (0.1 mg ml(-1)), associated with 85.7
      J cm(-2) of a light-emission diode, was evaluated on the viability of 5-d
      biofilms. Both the number of micro-organisms and the concentration of water
      insoluble polysaccharide increased with the age of the biofilms. A significant
      reduction ( approximately 95%) in viability was observed for S. mutans and S.
      sobrinus biofilms following photosensitization, with a > 99.9% reduction in the
      viability of S. sanguinis biofilms. In conclusion, a biofilm model was shown to
      be suitable for studying changes in bacterial numbers and enamel mineralization
      and for demonstrating the potential value of photosensitization in the control of
      in vitro biofilms.

PMID- 16460344
TI  - Age-associated changes in viscoelastic properties of the bovine temporomandibular
      joint disc.
AB  - To test the hypothesis that compressive properties of the temporomandibular joint
      (TMJ) disc change with age, we investigated its viscoelastic properties and
      stress-relaxation behavior under compression. Compressive stress-relaxation tests
      were performed in different regions of bovine discs of various ages. For each
      disc, specimens were derived from three different regions (anterior, central, and
      posterior). For four strain levels (5, 10, 15, and 20%), a stress-relaxation test
      was conducted over a 5-min period. Values of the instantaneous modulus, E(0),
      appeared to be larger in the anterior than in the posterior region of the disc,
      irrespective of age. The E(0) value increased with age, especially in the central
      region. Values of the relaxed modulus, E(R), also increased significantly with
      age. There were no regional differences in values of the relaxed modulus. Under
      stress-relaxation, the relaxation time became longer with age, especially in the
      posterior region. The results suggest that the compressive properties,
      instantaneous and relaxed moduli, increase with age, while the relaxation time
      becomes longer. This implies that the TMJ disc becomes harder with age.
      Furthermore, the compressive properties of the TMJ disc are region-specific. As a
      result of the harder disc, it is likely that the TMJ becomes more vulnerable to
      secondary damage, such as fracture and tissue degradation.

PMID- 16460345
TI  - Mechanical behavior of bovine periodontal ligament under tension-compression
      cyclic displacements.
AB  - In the present study, the mechanical response of bovine periodontal ligament
      (PDL) subjected to displacement-controlled tension-compression harmonic
      oscillations and subsequent rupture was examined. Specimens including dentine,
      cementum, PDL, and alveolar bone were extracted from different depths and
      locations of bovine first molars. They were immersed in a saline solution at room
      temperature and clamped on their bone and dentine extremities. The samples were
      tested at +/-35% of the PDL's width, with a frequency of 1 Hz. The mechanical
      parameters evaluated were hysteresis, phase lag, and the modulus of the stress
      stretch ratio curves in tension and compression. The tensile strength and the
      corresponding stretch ratio were also recorded. Stress-stretch ratio curves
      indicated a non-linear, time-dependent response with hysteresis and
      preconditioning effects. The hysteresis and phase lag in compression were much
      higher than in tension, suggesting that the dissipated energy was higher in
      compression than in tension. The root depth and location did not play essential
      roles for the tension or compression data, with the exception of limited
      statistical differences for tensile strength and corresponding stretch ratio.
      Thus, biological variability in the specimens, as a result of different bone
      contours, PDL width, and fiber orientation, did not affect the energy-absorbing
      capacity of the PDL. The evolution of the stress rate with stress demonstrated a
      constant increase of stiffness with stress. The stiffness values were twofold
      higher in tension than in compression. The data also showed that the stiffness of
      the PDL was comparable with data reported for other soft tissues.

PMID- 16460346
TI  - Fluoride's effect on human dentin ultrasound velocity (elastic modulus) and
      tubule size.
AB  - Despite fluoride (F) use in caries prevention, not much is known about its
      effects on tooth quality. This study evaluated the effect of tooth F
      concentration ([F]) on selected dentin structural and mechanical properties.
      Third molars (n = 136) from Toronto, which has 1 part per million (p.p.m.) water
      [F], Montreal (0.2 p.p.m. water [F]), and Fortaleza (Brazil) (0.7 p.p.m. water
      [F]), were analyzed for [F], dental fluorosis (DF) severity, ultrasound velocity,
      and dentin tubule size and density. The enamel [F] was found to vary between 32
      and 940 p.p.m., the dentin [F] was found to vary between 110 and 860 p.p.m.,
      while the DF severity varied between TF0 and TF4. The enamel [F] showed no
      correlation with dentin [F], DF severity, ultrasound velocity, dentin tubule size
      or density. The dentin [F] correlated with DF severity, dentin tubule size, and
      ultrasound velocity. DF severity showed a correlation with dentin [F] and
      ultrasound velocity. It was concluded that dentin [F] is an indicator of dentin
      structural properties (dentin tubule size and ultrasound velocity), while DF
      severity is an indicator of dentin mechanical properties (ultrasound velocity).

PMID- 16460347
TI  - Substitution of bovine dentine sialoprotein with chondroitin sulfate
      glycosaminoglycan chains.
AB  - Dentine sialoprotein (DSP) represents 5-8% of all non-collagenous proteins
      present in the tooth, but, together with dentine phosphoprotein, has been shown
      to be vital for correct tooth formation. Recently, the existence of a highly
      glycosylated form of porcine DSP has been reported and it was shown to possess
      glycosaminoglycan (GAG) chains. The current investigation confirms that this is
      also the case for bovine DSP and has further characterized these carbohydrates.
      Dentine sialoprotein was purified from bovine dentine extracts by anion exchange
      chromatography and identified by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), western blotting, and mass spectroscopy. An increase
      in molecular mass was observed, from 120 kDa to greater than 250 kDa, with a
      corresponding rise in anionic strength. Cellulose acetate electrophoresis and
      western blotting indicated the presence of chondroitin sulfate GAG chains within
      these dentine fractions. Further examination using sequential digestion with
      chondroitinase AC and N-glycosidase cleaved the samples first to 95 kDa and then
      to 80 kDa, respectively, confirming a high level of glycosylation. These results
      support the classification of bovine DSP as a proteoglycan, and that the
      carbohydrate substitutions may contribute to the functional properties of DSP.

PMID- 16460348
TI  - Immunohistochemical localization of transcription factor Sp3 during dental enamel
      development in rat tooth germ.
AB  - Sp3, a member of the Sp family of transcription factors, has previously been
      thought to be ubiquitously expressed, and its expression pattern in tooth
      development is not clear. This study was carried out to investigate the
      immunolocalization of Sp3 during the development of rat tooth germs. Sprague
      Dawley rats at ages of 1, 3, 7, 10, and 14 d were used to represent different
      stages of tooth development. First mandibular molar tooth germs were sectioned
      and studied by immunohistochemistry. Sp3 was found to be localized within the
      nuclei of cells in developing tooth germs; however, ameloblast nuclei showed
      variable intensities at different developmental stages. At the same time, the
      positive signals in odontoblast nuclei remained stable. The results suggest that
      Sp3 may play a role in the development of teeth, specifically in the
      transcription of enamel-specific genes.

PMID- 16460349
TI  - Human-mediated foot-and-mouth disease epidemic dispersal: disease and vector
      clusters.
AB  - Disease clusters were retrospectively explored at national level using a geo
      referenced dataset from the 2001 Uruguayan Foot-and-Mouth Disease (FMD) epidemic.
      Disease location and time (first 11 epidemic weeks) were analysed across 250
      counties (of which 160 were infected), without and with control for human
      mobility related factors (human population and road densities). The null
      hypothesis of random disease distribution over space and/or time was assessed
      with: (i) purely temporal; (ii) purely spatial; and (iii) space/time tests. At
      least within epidemic weeks 2 and 6, a principal disease cluster was observed in
      33 contiguous counties (P < 0.01). Two secondary clusters, located at >100 km
      from each other, were also observed (P < 0.01). The purely spatial test that
      controlled for human population density identified two non-contiguous clusters (P
      < 0.01). Space and time analysis also revealed the same 33 counties as members of
      the principal cluster, of which 31 were also clustered when human population was
      controlled (P < 0.01). No clusters were reported by the spatial test when road
      density was assessed. The hypothesis that human mobility related factors
      autocorrelate with disease was empirically supported by two pieces of
      information: (i) removal of human population/road densities eliminated >93.9% of
      the counties included in the principal disease cluster; and (ii) statistically
      significant correlations (P < 0.05) were observed in the first three epidemic
      weeks between road density and the number of cases. Clusters where human
      population density was associated with 47% greater number of cases/sq. km than
      that of the principal cluster indicated possible roles as disease vectors (vector
      clusters). Selective control policy in vector clusters is recommended. Periodic
      (i.e. weekly) cluster and correlation analyses of both disease and other
      covariates may facilitate disease surveillance and help design space-specific
      control policy.

PMID- 16460350
TI  - Oesophagoscopy and detection of viral nucleic acids in oesophageal biopsies--A
      contribution to BVDV diagnosis.
AB  - The endoscopic appearance of the oesophagus of animals infected with bovine virus
      diarrhoea virus (BVDV) but without signs of acute mucosal disease (MD) was
      investigated for any common or 'early warning' lesions. Thirty-seven BVDV
      infected animals [36 persistently infected (PI) and one transiently infected]
      were examined clinically and endoscopically for typical erosions of the oronasal
      and oesophageal mucosa, respectively. During oesophagoscopy, mucosal biopsies
      were taken and tested for pestivirus-specific nucleic acids by reverse
      transcription polymerase chain reaction (RT-PCR). The results were compared with
      those of RT-PCR with various sample materials (blood, nasal and conjunctival
      swabs and faecal samples) usually used for routine diagnosis of BVDV infection.
      The average age of the 36 PI animals was 13.5 months, eight animals were 24
      months or older. None of the PI animals had clinically visible erosions of the
      oronasal mucous membranes. During oesophagoscopy, all animals showed a reddening
      but unexpectedly no erosions or ulcerations of the oesophageal mucosa. Although
      in 21 of 36 PI animals all samples tested positive, the oesophageal biopsies were
      with no exception constantly RT-PCR positive in contrast to all other materials
      investigated. Remarkably, in the transiently infected animal all samples tested
      negative except for the oesophageal biopsy. Hence, this infection would have been
      missed by conventional diagnostic sampling.

PMID- 16460351
TI  - Immune complex-based vaccine for pig protection against parvovirus.
AB  - The insoluble immune complexes (ICs) were prepared under the conditions of double
      immunodiffusion in gel, using the suspension of the ultrasound treated PK-15 cell
      line infected with porcine parvovirus (PPV) containing both viral particles and
      viral proteins, as well as pig or rabbit anti-PPV polyclonal immune sera. The
      immunodiffusion performed in an agarose gel allows only viral subunits with a
      molecular mass equal to or less than 1000 kDa, rather than the viral particles,
      to diffuse through the gel and reach the point where the immunoprecipitate is to
      be formed. The immunoprecipitation under the conditions of the diffusion ensures
      the optimal, i.e. equimolar ratio of both immunoprecipitating components,
      antibody/antigen in the IC. The sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and the Western blot analyses showed the ICs were composed of two
      proteins, a protein in which molecular mass corresponded to the VP2 of the PPV
      and a protein with a molecular mass of the IgG. This suggests that the ICs are
      mainly composed of the VP2 antigen and IgG class antibodies. The potency of the
      IC-vaccines prepared in the form of a water-in-oil-in-water emulsion was compared
      with that of a commercially available, inactivated oil vaccine. The vaccination
      of gilts, 6 weeks before mating, with the IC containing allogeneic pig
      antibodies, resulted in the development of high and long-lasting anti-PPV
      antibody titres, similar to those generated by the licenced vaccine (P > 0.01).
      The content of the virus material administered by the IC was twice lower than
      that in the licenced vaccine. Neither systemic nor local reactions were observed
      in the gilts during the period of the trial with the IC vaccine. The number of
      viable piglets per litter varied between 9 and 12 and no signs of the PPV
      infection were detected. Rabbits were used as one of the alternative laboratory
      animal models accepted for the testing of the vaccine against the PPV. The rabbit
      humoral immune response generated by the IC containing the allogeneic antibodies
      were higher than that generated by the ICs containing the xenogeneic pig
      antibodies. It was similar to that generated by two-times higher content of the
      virus material administered by a commercially available vaccine. The IC-based
      vaccines belong to non-replicating, subunit vaccines, which are both ecologically
      convenient and the safest vaccines of all.

PMID- 16460352
TI  - A serological survey of selected pathogens in wild boar in Slovenia.
AB  - Serum samples collected from 178 shot wild boars (Sus scrofa) were tested for the
      presence of antibodies against classical swine fever virus, Aujeszky's disease
      virus (ADV), porcine reproductive and respiratory syndrome virus, porcine
      respiratory coronavirus (PRCV), transmissible gastroenteritis virus, swine
      influenza virus, porcine parvovirus (PPV), swine vesicular disease virus,
      Actinobacillus pleuropneumoniae (APP), Mycoplasma hyopneumoniae, Salmonella spp.,
      Brucella spp. and Haemophilus parasuis (HPS) throughout Slovenia during the
      hunting season 2003/2004. The number of samples corresponds to 3% of the total
      hunting bag. By enzyme-linked immunosorbent assay (ELISA) antibodies against ADV
      were detected in 55 sera (31%), against PRCV in five sera (3%), PPV in 87 sera
      (49%), APP in 93 sera (52%), M. hyopneumoniae in 38 sera (21%), Salmonella spp.
      in 85 sera (47%) and HPS in 33 sera (18%).

PMID- 16460353
TI  - Multidrug resistance and distribution of Salmonella serovars in slaughtered pigs.
AB  - The present study was undertaken to estimate the occurrence and distribution of
      multidrug resistance (MDR) among Salmonella serovars isolated from slaughtered
      pigs at Debre Zeit, Ethiopia. A total of 501 different samples were examined of
      which 42 (41.6%) of 101 mesenteric lymph nodes, 22 (21.8%) of 101 tongues, 17
      (16.8%) of 101 caecal contents, 11 (11.1%) of 99 livers and two (2%) of 99 muscle
      (diaphragm and abdomen) samples were Salmonella positive. Of the 94 Salmonella
      isolates representing 15 different serovars, 69 (73.4%) were multidrug resistant
      (resistance to two or more antimicrobials). Among the Salmonella serovars a high
      level of MDR was observed in S. Hadar, S. Kentucky, S. Blockley and S.
      Enteritidis mainly to tetracycline (88.6%), streptomycin (82.9%), nitrofurantoin
      (74.3%), nalidixic acid and ciprofloxacin (42.9% each), sulfisoxazole (21.1%) and
      spectinomycin (20%). The pattern of MDR varied from two to eight antimicrobials
      among the resistant Salmonella serovars. The common profiles of resistance among
      the MDR serovars were the combined resistance to nitrofurantoin, streptomycin and
      tetracycline (R type NitStrTet, 51.4%), ciprofloxacin, nalidixic acid and
      nitrofurantoin (R type CipNalNit, 10%), ciprofloxacin, nalidixic acid,
      spectinomycin, streptomycin, sulfisoxazole and tetracycline (R type
      CipNalSptStrSulTet, 14.3%) and to ciprofloxacin, kanamycin, nalidixic acid,
      neomycin, nitrofurantoin, streptomycin and tetracycline (R type
      CipKanNalNeoNitStrTet, 10%). Results of the present study indicate the widespread
      occurrence and distribution of MDR Salmonella serovars in slaughtered pigs which
      could be a potential source of human MDR Salmonella infections.

PMID- 16460354
TI  - Lpp34, a novel putative lipoprotein from Mycobacterium avium subsp.
      paratuberculosis.
AB  - A Mycobacterium avium subsp. paratuberculosis expression library in lambda ZAP
      was screened with immunized mice sera. One clone was selected, sequenced and
      further characterized. The sequence analysis of the hypothetical open-reading
      frame (ORF) predicts a protein of 20.8 kDa with a probable signal sequence
      compatible with Cys-acylation at Cys24, characteristic of lipoproteins. In
      consequence, the protein was termed Lpp34. Recombinant expression of Lpp34 was
      achieved by cloning the lpp34 gene into the histidine-tag expression vector pRSET
      A. Western blot analysis showed a protein band with a molecular weight of 34 kDa.
      The native protein was localized in the membrane fraction of M. avium subsp.
      paratuberculosis and extracted in the detergent phase of Triton X-114. Southern
      blot and polymerase chain reaction showed that the gene is absent from all the
      non-M. avium complex mycobacterial genomes tested. Humoral reactivity using
      bovine sera demonstrated that this protein is widely recognized by both the
      infected and non-infected animals. This could partly be due to the conserved
      sequence in close-related environmental bacteria such as M. avium subsp. avium
      and to the presence of a conserved epitope in other bacteria such as Escherichia
      coli. In conclusion, these findings show that Lpp34 is a membrane protein and a
      putative lipoprotein present in M. avium complex mycobacteria and absent in the
      M. tuberculosis complex.

PMID- 16460355
TI  - Detection of Lawsonia intracellularis in wild boar and fallow deer bred in one
      game enclosure in the Czech Republic.
AB  - The prevalence of Lawsonia intracellularis between wild boar (Sus scrofa) and
      fallow deer (Dama dama) bred in one game reserve was investigated using the
      nested PCR method. In the study, 88 clinically healthy wild boars of different
      age categories and two fallow deer bagged in the game reserve were examined.
      Lawsonia intracellularis was demonstrated in the mucous membrane of the intestine
      of eight (9.1%) wild boars and one fallow deer. Of the nine wild boar whose
      tissues of corresponding lymph nodes were examined in addition to the mucous
      membrane of the ileum, one tested positive for the microorganism. A relationship
      between the occurrence of L. intracellularis and age of wild boar was
      demonstrated. Because wild boar and fallow deer are bred together in one game
      reserve, the possibility of inter-species transfer of L. intracellularis should
      be borne in mind.

PMID- 16460356
TI  - Application of PCR for detection of Clostridium botulinum type D in bovine
      samples.
AB  - Diagnosis of botulism in cows is obtained by detecting the neurotoxin and/or
      Clostridium botulinum in the suspected animal. The standard method for detecting
      the toxin is the mouse bioassay. However, in recent years, the use of mice has
      become very costly and inconvenient in some facilities, and public pressure has
      been increasing to find alternatives to live animal bioassays. In this
      manuscript, we describe the use of the polymerase chain reaction (PCR) procedures
      in the diagnosis field cases of bovine type D botulism. Bovine samples from
      clinical cases diagnosed as C. botulinum type D according by clinical symptoms
      and bioassay resulted in expected PCR product ( approximately 497 bp) similar to
      the C. botulinum type D NCTC 8265 strain while the gene product was confirmed by
      sequence data.

PMID- 16460357
TI  - Prevalence of antibodies to pestiviruses in goats in Austria.
AB  - Serological investigations were carried out to determine the prevalence of
      pestiviral infections in goats in Austria, and to investigate the possible
      relations to herd management practices. The prevalence of antibodies to
      pestiviruses was investigated in 549 goats in 80 flocks from four regions of
      Austria. The examination for antibodies was performed using an indirect enzyme
      linked immunosorbent assay detecting antibodies to the border disease virus (BDV)
      and bovine viral diarrhoea virus (BVDV). The observed individual prevalence was
      11.5% and the flock prevalence was 31.3%. Comparative neutralization studies on
      the 63 seropositive samples with BVDV-1, BVDV-2 and the BDV yielded in 32 samples
      higher titres (> or =4-fold) to BVDV-1 and in two samples to BDV. The remaining
      samples did not show distinct differences in antibody titres against the
      pestivirus strains tested because of the cross-reactions. There was a significant
      (P < 0.05) association between the prevalence of antibodies to pestiviruses and
      the presence of cattle on the farm. Significant (P < 0.05) geographical
      variations in individual prevalence were obtained, ranging from 3.5% in lower
      Austria to 20.2% in Vorarlberg.

PMID- 16460358
TI  - Outbreak of disseminated zygomycosis and concomitant pulmonary aspergillosis in
      breeder layer cockerels.
AB  - Disseminated zygomycosis and concomitant pulmonary aspergillosis were diagnosed
      in breeder layer cockerels. Five- to 9-week-old breeder layer cockerels with a
      history of an increased mortality rate were presented to a diagnostic laboratory
      for examination. On necropsy, large, multifocal, firm, tan, nodules were observed
      in the lungs, air sacs, peritoneum, livers, spleens and kidneys. On
      histopathology, mixed populations of zygomycetes and Aspergillus hyphae were
      observed in the granulomas in the lungs, and zygomycete hyphae were observed in
      the granulomas in the air sacs, peritoneum, livers, spleens and kidneys. No
      bacteria were isolated from any of the lesions. Aspergillus fumigatus was
      isolated from the lung lesions only and hyphae that were consistent with those of
      a Rhizopus spp. were isolated from the lesions in several organs. Pullets, which
      were kept together with the cockerels from the day they were hatched, were not
      affected. The absence of infection in the pullets, which were kept together with
      the cockerels, suggests that the cockerels were either infected during
      incubation, with the fungi penetrating the egg shell, or that they were infected
      during hatching before they were mixed with the pullets.

PMID- 16460359
TI  - Buying time II: an economic evaluation of a joint NHS/Social Services residential
      rehabilitation unit for older people on discharge from hospital.
AB  - The study's aim was to investigate the cost-effectiveness of an NHS/Social
      Services short-term residential rehabilitation unit (a form of intermediate care)
      for older people on discharge from community hospital compared with 'usual'
      community services. An economic evaluation was conducted alongside a prospective
      controlled trial, which explored the effectiveness of a rehabilitation unit in a
      practice setting. The aim of the unit was to help individuals regain
      independence. A matched control group went home from hospital with the
      health/social care services they would ordinarily receive. The research was
      conducted in two matched geographical areas in Devon: one with a rehabilitation
      unit, one without. Participants were recruited from January 1999 to October 2000
      in 10 community hospitals and their eligibility determined using the unit's
      strict inclusion/exclusion criteria, including 55 years or older and likely to
      benefit from a short-term rehabilitation programme: potential to improve,
      realistic, achievable goals, motivation to participate. Ninety-four people were
      recruited to the intervention and 112 to the control group. Details were collated
      of the NHS and Social Services resources participants used over a 12-month follow
      up. The cost of the resource use was compared between those who went to the unit
      and those who went straight home. Overall, costs were very similar between the
      two groups. Aggregated mean NHS/Social Services costs for the 12 months of follow
      up were pound 8542.28 for the intervention group and pound 8510.68 for the
      control. However, there was a clear 'seesaw' effect between the NHS and Social
      Services: the cost of the unit option fell more heavily on Social Services (pound
      5011.56, whereas pound 3530.72 to the NHS), the community option more so on the
      NHS (pound 5146.74, whereas pound 3363.94 to Social Services). This suggests that
      residential rehabilitation for older people is no more cost-effective over a year
      after discharge from community hospital than usual community services. The
      variability in cost burden between the NHS and Social Services has implications
      for 'who pays' and being sure that agencies share both pain and gain.

PMID- 16460360
TI  - Opportunities for independent living using direct payments in mental health.
AB  - Mental health service users have yet to reap the benefits of greater choice,
      control and independent living, which direct payments have facilitated in other
      groups of community care users, particularly people with physical disabilities.
      To redress this imbalance a national pilot to promote direct payments to people
      with mental health needs in five local authority sites across England was set up
      and evaluated. The evaluation used a multi-method approach incorporating both
      qualitative and quantitative data, including individual semi-structured
      interviews and group discussions with key stakeholders across the pilot sites.
      This article draws on findings from the pilot evaluation to provide a preliminary
      understanding of how applicable the independent living philosophy is to mental
      health and what opportunities direct payments offer for service users. When given
      the opportunity, service users were able to use direct payments creatively to
      meet a range of needs in ways which increased their choice, control and
      independence. This suggests that the benefits of greater independent living
      through direct payments may be realisable in mental health. However, a number of
      ways in which the principles of direct payments in mental health could be
      'downgraded' were identified. The evaluation results indicate that a thorough
      understanding of the independent living philosophy needs to be developed in the
      context of mental health.

PMID- 16460361
TI  - Decision-making in community-based paediatric physiotherapy: a qualitative study
      of children, parents and practitioners.
AB  - Approaches to practice based on partnership and shared decision-making with
      patients are now widely recommended in health and social care settings, but less
      attention has been given to these recommendations in children's services, and to
      the decision-making experiences of non-medical practitioners and their patients
      or clients. This study explored children's, parents' and practitioners' accounts
      of shared decision-making in the context of community-based physiotherapy
      services for children with cerebral palsy. Semi-structured interviews were
      conducted with 11 children with cerebral palsy living in an inner city area of
      northern England, and with 12 of their parents. Two focus groups were conducted
      with 10 physiotherapy practitioners. Data were analysed using the constant
      comparative method. When asked explicitly about decision-making, parents,
      children and practitioners reported little or no involvement, and each party saw
      the other as having responsibility for decisions. However, when talking in more
      concrete terms about their experiences, each party did report some involvement in
      decision-making. Practitioners' accounts focused on their responsibility for
      making decisions about resource allocation, and thereby, about the usefulness and
      intensity of interventions. Parents indicated that these practitioner-led
      decisions were sometimes in conflict with their aspirations for their child.
      Parents and children appeared to have most involvement in decisions about the
      acceptability and implementation of interventions. Children's involvement was
      more limited than parents'. While parents could legitimately curtail unacceptable
      interventions, children were mostly restricted to negotiating about how
      interventions were implemented. In these accounts the involvement of each party
      varied with the type of issue being decided and decision-making appeared more
      unilateral than shared. In advocating shared decision-making, greater
      understanding of its weaknesses as well as its strengths, and greater clarity
      about the domains that are suitable for a shared decision-making approach and the
      roles of different parties, would seem a helpful step.

PMID- 16460362
TI  - Personalised social care for adults with disabilities: a problematic concept for
      frontline practice.
AB  - This paper explores the complexities and contradictions of frontline practice
      that pose problems for personalised social care through enhanced choice. It draws
      on semi-structured interviews with community care workers, social workers,
      occupational therapists and care managers in a social service department.
      Practitioners interviewed were asked about their current assessment and
      documentation system, including the assessment documents currently used; how they
      approached information gathering and the topics they explored with service users;
      and their experience of documenting assessment and care management. The paper
      argues that the validity and sustainability of personalised social care in
      frontline practice relies on developing a thorough understanding of the complex
      and implicit assessment processes operating at the service user/practitioner
      interface and the inevitable tensions that arise for practitioners associated
      with the organisational context and broader service environment. The findings
      demonstrate the variability among practitioners in how they collect information
      and more importantly, the critical role practitioners occupy in determining the
      kinds of topics to be explored during the assessment process. In so doing, it
      shows how practitioners can exert control over the decision-making process. More
      importantly, it provides some insight into how such processes are shaped by the
      constraints of the organisational context and broader service environment.
      Complexities and contradictions may be an inherent part of frontline practice.
      The issues discussed in this paper, however, highlight potential areas that might
      be targeted in conjunction with implementing personalised social care through
      enhanced choice for people with disabilities.

PMID- 16460363
TI  - Older people in Sweden with various degrees of present quality of life: their
      health, social support, everyday activities and sense of coherence.
AB  - Public health policies in most European countries are concerned with how to keep
      older people living independently with a qualitatively good life in the community
      as long as possible. However, knowledge about what may characterise those
      seemingly 'healthy' older people is sparse. The aim of the study was to
      investigate the characteristics of a sample of people (75+) reporting various
      degrees of Quality of Life (QoL) with respect to QoL in different areas, as well
      as self-rated health, health problems, social support, everyday activities and
      sense of coherence. A postal questionnaire was sent out in spring 2001 to a
      randomly selected population-based sample (n= 600) in the southern parts of
      Sweden. A two-step cluster analysis was performed (n= 385, mean age 84.6, SD =
      5.7) with 'present QoL' as clustering attribute. Three groups were disclosed,
      classified as high, intermediate and low present QoL, of which 33.8% could be
      regarded being at risk of low QoL. Those with low present QoL (18.4%) were the
      oldest and most vulnerable, a majority were women with 'poor or bad' self-rated
      health, high frequencies of health problems, low total QoL, low social support
      and sense of coherence and less physically active. Those with high present QoL
      (47.8%) reported more 'excellent or good' self-rated health, physical activity,
      satisfactory social support and higher sense of coherence and total QoL than the
      other two groups. Those with intermediate present QoL (33.8%) had more of 'poor
      or bad' self-rated health, more health problems were less physically active, had
      lower total QoL and sense of coherence, and less social support than those with
      high present QoL. The sample seemed to reflect the ageing process in that the
      respondents were at different stages of ageing. However, the fact that the level
      of social support, sense of coherence and self-rated health followed the same
      curve as QoL may indicate that some are more vulnerable to low present QoL given
      the same health and these should be targeted in preventive programmes since they
      report low QoL.

PMID- 16460364
TI  - 'It's very difficult to get respite out here at the moment': Australian findings
      on end-of-life care for Indigenous people.
AB  - Whilst access to respite care has been found to represent an important source of
      support for terminally ill patients and their families, the availability of these
      services to Indigenous Australians has to date remained undocumented. This
      potential need for respite in Indigenous communities was explored as part of a
      National Health and Medical Research Council (NH&MRC) funded study designed to
      develop an innovative model for Indigenous palliative care. The data needed for
      model development were collected through a series of open-ended, qualitative
      interviews conducted with a cross-section of consumers and health professionals
      within the Northern Territory, Australia. The findings reflected a serious need
      for Indigenous respite services, coupled with a severe deficiency in the present
      availability of these services, especially within rural and regional areas. This
      lack of local respite services was documented to be negatively impacting upon the
      ability of carers to fulfil their caring duties and was found placing undue
      physical, emotional and economic stress upon carers, patients and their families.
      Furthermore, the lack of access to local respite services documented was found to
      be forcing rural and regional patients to relocate to metropolitan areas away
      from the family, community and land to which strong ties are held. The lack of
      Indigenous respite services was also found to obstruct patients' and carers'
      wishes for death to occur in the local community, rather than in far away cities.
      Significant obstacles were found to be hindering the provision of respite care to
      Indigenous Australians, namely beliefs about families looking after their own,
      resource restrictions, limited staff availability in local areas, as well as
      problems associated with hostel use in metropolitan areas. The conclusions drawn
      from this study suggest the importance of tackling the obstacles preventing local
      respite services being established in areas close to where patients and carers
      live.

PMID- 16460365
TI  - Developing homelessness prevention practice: combining research evidence and
      professional knowledge.
AB  - This paper presents recommendations of three kinds for the development of
      homelessness prevention: for practice changes, for the concerted development of
      evidence on the effectiveness of different measures, and for a more systematic
      approach to the identification and dissemination of good practice. The
      recommendations were developed through consultation with health-care, social
      service and housing provider staff. They were asked to comment on the results of
      a study of 131 newly homeless people, which showed that there were five prevalent
      'packages of reasons' that created distinctive 'pathways' into homelessness and
      concluded that some cases were preventable. This article outlines the principles
      of homelessness prevention and recent British policy initiatives in the field,
      summarises the research methodology and relevant findings, and describes the
      consultation. The final section discusses the discrepancy between the high
      priority that homelessness prevention currently receives and the primitiveness of
      both the evidence base and the arrangements for good practice dissemination.

PMID- 16460366
TI  - Variations in duty arrangements to respond to concerns about children's welfare.
AB  - Reception and initial contact arrangements and practices in social services play
      a key role in safeguarding children and providing an avenue for the public and
      professionals to report concerns about a child's welfare. This paper reports on
      findings from a small-scale study, commissioned in the wake of the Laming Inquiry
      into the circumstances surrounding the death of Victoria Climbie. The aim of the
      study was an exploration of the arrangements local authorities had in place in
      early 2004 to receive referrals from the public and professional sources, and to
      report on duty team managers' levels of satisfaction with these arrangements. It
      drew on interviews with 70 social work managers responsible for daytime and out
      of-hours duty services in 28 English local authorities. The authors argue that,
      while the Inquiry recommendations to improve the organisation of initial contact
      with social services in the event of concerns about a child's welfare remain
      important, wide variations exist in practice. The paper concludes with a
      discussion of possible contributory factors for such variation, and policy and
      practice measures that could address the variation.

PMID- 16460367
TI  - Supporting young mothers into education, employment and training: assessing
      progress towards the target.
AB  - The government has set a target of increasing the participation of teenage
      mothers in education, employment and training (EET) to 60% by 2010 to reduce
      their risk of long-term social exclusion. This paper presents the findings of a
      qualitative research project conducted in the South West region of England to
      establish the tracking practices employed by practitioners working with young
      parents to ascertain whether and to what extent teenage parents are engaged in
      EET. The range of support that is currently needed by and provided to teenage
      parents when returning to or continuing their EET was also investigated. Semi
      structured telephone interviews were conducted with 24 participants from a
      unitary authority, county and city within the region; participants were working
      in a variety of professional roles with responsibilities for teenage parents. The
      results show that in the South West there are currently no standard procedures or
      practices in place for effectively tracking the participation of teenage parents
      in EET. There was evidence of a good understanding of the needs of young parents
      amongst practitioners and that a variety of support was being provided to them.
      However, it needs to be understood, and addressed, that having contact with young
      parents and providing them with support does not necessarily lead to the
      standardised information that is needed in order to assess progress towards the
      target. We conclude that in order to assess in a meaningful way progress towards
      the target of 60% participation by 2010, a clear protocol for the collection and
      collation of information--and responsibility for this--needs to be developed and
      implemented.

PMID- 16460369
TI  - Ten dimensions of health and their relationships with overall self-reported
      health and survival in a predominately religiously active elderly population: the
      cache county memory study.
AB  - OBJECTIVES: To document the extent of healthy aging along 10 different dimensions
      in a population known for its longevity. DESIGN: A cohort study with baseline
      measures of overall self-reported health and health along 10 specific dimensions;
      analyses investigated the 10 dimensions as predictors of self-reported health and
      10-year mortality. SETTING: Cache County, Utah, which is among the areas with the
      highest conditional life expectancy at age 65 in the United States. PARTICIPANTS:
      Inhabitants of Cache County aged 65 and older (January 1, 1995). MEASUREMENTS:
      Self-reported overall health and 10 specific dimensions of healthy aging:
      independent living, vision, hearing, activities of daily living, instrumental
      activities of daily living, absence of physical illness, cognition, healthy mood,
      social support and participation, and religious participation and spirituality.
      RESULTS: This elderly population was healthy overall. With few exceptions, 80% to
      90% of persons aged 65 to 75 were healthy according to each measure used.
      Prevalence of excellent and good self-reported health decreased with age, to
      approximately 60% in those aged 85 and older. Even in the oldest old, the
      majority of respondents were independent in activities of daily living. Although
      vision, hearing, and mood were significant predictors of overall self-reported
      health in the final models, age, sex, and cognition were significant only in the
      final survival models. CONCLUSION: This population has a high prevalence of most
      factors representing healthy aging. The predictors of overall self-reported
      health are distinct from the predictors of survival in this age group and, being
      potentially modifiable, are amenable to clinical and public health efforts.

PMID- 16460370
TI  - Predictive validity of measures of comorbidity in older community dwellers: the
      Insufficienza Cardiaca negli Anziani Residenti a Dicomano Study.
AB  - OBJECTIVES: To compare the ability of five measures of comorbidity to predict
      mortality and incident disability in basic activities of daily living (BADLs) in
      unselected older persons. DESIGN: An assessment of the data obtained from the
      Insufficienza Cardiaca negli Anziani Residenti a Dicomano (ICARe Dicomano) Study,
      a longitudinal epidemiological survey on heart failure in older people. SETTING:
      Dicomano, a small, rural town near Florence, Italy. PARTICIPANTS: The entire
      population aged 65 and older living in Dicomano, Italy, was enrolled in the ICARe
      Dicomano Study. MEASUREMENTS: At baseline (1995), comorbidity was quantified in
      688 participants, based on clinical diagnoses, using disease count (DC), Charlson
      Comorbidity Index (CCI), Index of Co-Existent Diseases (ICED), and Geriatric
      Index of Comorbidity (GIC), or on drug use, using Chronic Disease Score (CDS).
      Incident ADL disability was assessed in 1999 and vital status in 2004. RESULTS:
      Mortality increased with the severity of comorbidity, with hazard ratios around 2
      when comparing the highest and the lowest quartiles of DC, CCI, and ICED in Cox
      regressions adjusted for age, sex, and physical and cognitive performance.
      Prediction of mortality with GIC and CDS was only borderline significant. All
      measures predicted incident ADL disability; the strongest risk gradient (hazard
      ratio = 8.2 between the highest and lowest quartiles) was observed with ICED.
      Physical and, to a minor extent, cognitive performance added significantly to
      predicting mortality and incident BADL disability. CONCLUSION: All the measures
      of comorbidity predicted death and BADL disability in older community dwellers.
      DC, CCI, and ICED performed better than GIC and CDS. Physical performance
      measures are strong, independent contributors to the prediction of these
      outcomes.

PMID- 16460371
TI  - Influenza and pneumococcal vaccination in older veterans: results from the
      behavioral risk factor surveillance system.
AB  - OBJECTIVES: To compare influenza and pneumococcal vaccination rates of older
      veterans with those of nonveterans and to compare vaccination rates of veterans
      who receive care at U.S. Department of Veterans Affairs (VA) medical centers with
      those of veterans who do not. DESIGN: Cross-sectional population-based study.
      SETTING: United States and territories. PARTICIPANTS: Persons aged 65 and older
      who participated in the 2003 Behavioral Risk Factor Surveillance System.
      MEASUREMENTS: Telephone survey of sociodemographics factors, including veteran
      status and VA care, health and behavioral characteristics, and influenza and
      pneumococcal vaccine use. RESULTS: Thirty percent of adults aged 65 and older
      were veterans, and 21% of veterans reported receiving care at VA health
      facilities. Veterans, especially VA users, were older and described poorer self
      perceived health than nonveterans. Influenza and pneumococcal vaccination rates
      were higher for veterans than for nonveterans (74% vs 68% and 68% vs 63%,
      respectively, P < .001 for both) and for VA users than non-VA users (80% vs 72%
      and 81% vs 64%, respectively, P < .001 for both). For veterans, VA care was
      independently associated with influenza (odds ratio (OR) = 1.8, 95% confidence
      interval (CI) = 1.5-2.2) and pneumococcal (OR = 2.4, 95% CI = 2.0-2.9) vaccine
      use after adjusting for sociodemographics factors, perceived health status,
      diabetes mellitus, asthma, and smoking. Current smoking and black race were
      independent predictors of low influenza vaccine uptake. CONCLUSION: VA care was
      associated with improved influenza and pneumococcal vaccine coverage, although
      vaccination rates for all elderly veterans fell short of Healthy People 2010
      goals. Increased efforts to reach undervaccinated groups, particularly blacks and
      smokers, are warranted.

PMID- 16460373
TI  - Assessing the appropriateness of pain medication prescribing practices in nursing
      homes.
AB  - OBJECTIVES: To test a tool for screening the quality of nursing home (NH) pain
      medication prescribing. DESIGN: Validity and reliability of measurement tool
      developed for a pre/postintervention with untreated comparison group. SETTING:
      Six treatment NHs and six comparison NHs in rural and urban Colorado.
      PARTICIPANTS: NH staff, physicians, and repeated 20% random sample of each home's
      residents (N = 2,031). INTERVENTION: Nurse and physician education; NH internal
      pain team to champion better pain management using a pain vital sign,
      consultations, and rounds. MEASUREMENTS: An expert panel reviewed the Pain
      Medication Appropriateness Scale (PMAS) for content validity. Research assistants
      interviewed NH residents, assessed them for pain using standardized instruments,
      and reviewed their medical records for prescriptions and use of pain and adjuvant
      medication. Construct validity was assessed by comparing the PMAS of residents in
      pain with the PMAS of those not in pain and comparing scores in homes in which
      the intervention was more effective with those in which it was less effective,
      using the Fisher exact and Student t tests. Interrater and test-retest
      reliability were measured. RESULTS: The mean total PMAS was 64% of optimal. Fewer
      than half of residents with predictably recurrent pain were prescribed scheduled
      pain medication; 23% received at least one high-risk medication. PMAS scores were
      better for residents not in pain (68% vs 60%, P = .004) and in homes where
      nurses' knowledge of pain assessment and management improved or stayed the same
      during the intervention (69% vs 61%, P = .03). CONCLUSION: The PMAS is useful for
      assessing pain medication prescribing in NHs and elucidates why so many residents
      have poorly controlled pain.

PMID- 16460372
TI  - Benzodiazepine use and physical disability in community-dwelling older adults.
AB  - OBJECTIVES: To determine whether benzodiazepine use is associated with incident
      disability in mobility and activities of daily living (ADLs) in older
      individuals. DESIGN: A prospective cohort study. SETTING: Four sites of the
      Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS:
      This study included 9,093 subjects (aged > or =65) who were not disabled in
      mobility or ADLs at baseline. MEASUREMENTS: Mobility disability was defined as
      inability to walk half a mile or climb one flight of stairs. ADL disability was
      defined as inability to perform one or more basic ADLs (bathing, eating,
      dressing, transferring from a bed to a chair, using the toilet, or walking across
      a small room). Trained interviewers assessed outcomes annually. RESULTS: At
      baseline, 5.5% of subjects reported benzodiazepine use. In multivariable models,
      benzodiazepine users were 1.23 times as likely as nonusers (95% confidence
      interval (CI) = 1.09-1.39) to develop mobility disability and 1.28 times as
      likely (95% CI = 1.09-1.52) to develop ADL disability. Risk for incident mobility
      was increased with short- (hazard ratio (HR) = 1.27, 95% CI = 1.08-1.50) and long
      acting benzodiazepines (HR = 1.20, 95% CI = 1.03-1.39) and no use. Risk for ADL
      disability was greater with short- (HR = 1.58, 95% CI = 1.25-2.01) but not long
      acting (HR = 1.11, 95% CI = 0.89-1.39) agents than for no use. CONCLUSION: Older
      adults taking benzodiazepines have a greater risk for incident mobility and ADL
      disability. Use of short-acting agents does not appear to confer any safety
      benefits over long-acting agents.

PMID- 16460374
TI  - Therapeutic exercise and depressive symptoms after stroke.
AB  - OBJECTIVES: To examine the effect of exercise on depressive symptoms and the
      effect of baseline depressive symptoms on the benefits from exercise in stroke
      survivors who have completed acute rehabilitation. DESIGN: Planned secondary
      analysis of the data from a 9-month randomized, controlled trial. SETTING:
      Participant homes. PARTICIPANTS: One hundred stroke survivors who had completed
      acute rehabilitation. INTERVENTION: A progressive, structured, 3-month physical
      exercise program. MEASUREMENTS: Demographics, stroke characteristics,
      impairments, functional limitations, the Geriatric Depression Scale, the Stroke
      Impact Scale, and the Medical Outcomes Study 36-Item Short Form. RESULTS:
      Baseline rates of depressive symptoms and other stroke sequelae were similar
      between the two arms. Ninety-three participants were assessed immediately after
      the intervention (3 months after enrollment), and 80 were assessed 9 months after
      enrollment. Six (14%) of the exercise group and 16 (35.6%) of the usual-care
      group had depressive symptoms at 3 months (P = .03). At 9 months, three (7.5%) of
      the exercisers had significant depressive symptoms compared with 10 (25%) who
      received usual care (P = .07). Participants with and without baseline depressive
      symptoms had equivalent treatment-related gains in impairments and functional
      limitations, but only participants with depressive symptoms had improved quality
      of life. CONCLUSION: Exercise may help reduce poststroke depressive symptoms.
      Depressive symptoms do not limit gains in physical function due to exercise.
      Exercise may contribute to improved quality of life in those with poststroke
      depressive symptoms.

PMID- 16460375
TI  - The dynamic nature of mobility disability in older persons.
AB  - OBJECTIVES: To determine the rates of clinically meaningful transitions in
      mobility disability; evaluate how these transitions differ according to age, sex,
      and physical frailty; and depict the duration of the resulting episodes of
      mobility disability. DESIGN: Prospective cohort study. SETTING: General community
      in greater New Haven, Connecticut, from March 1998 to October 2004. PARTICIPANTS:
      Seven hundred fifty-four community-living older persons, aged 70 and older, who
      were nondisabled (i.e., required no personal assistance) in four activities of
      daily living. MEASUREMENTS: Mobility disability, defined as the inability to walk
      one quarter of a mile and to climb a flight of stairs, respectively without
      personal assistance, was assessed every month for up to 5 years. RESULTS: For
      both mobility tasks, rates per 1,000 person-months were higher for transitions
      from no disability to intermittent disability (34.7 for walking one quarter of a
      mile and 17.4 for climbing a flight of stairs), intermittent to continuous
      disability (52.0 and 42.5), continuous to intermittent disability (35.4 and
      31.5), and intermittent to no disability (68.6 and 85.4) than for other
      transitions. Older age, female sex, and physical frailty were associated with
      greater likelihood of transition to states of greater disability and lower
      likelihood of regaining independent mobility. CONCLUSION: Mobility disability in
      older persons is a highly dynamic process, characterized by frequent transitions
      between states of independence and disability. Programs designed to enhance
      independent mobility should focus not only on the prevention of mobility
      disability but also on the restoration and maintenance of independent mobility in
      older persons who become disabled.

PMID- 16460376
TI  - Epidemiology of gait disorders in community-residing older adults.
AB  - OBJECTIVES: To study the epidemiology of gait disorders in community-residing
      older adults and their association with death and institutionalization. DESIGN:
      Community-based cohort study. SETTING: Bronx County and the research center at
      Albert Einstein College of Medicine. PARTICIPANTS: The Einstein Aging study
      recruited 488 adults aged 70 to 99 between 1999 and 2001. At entry and during
      annual visits over 5 years, subjects received clinical evaluations to determine
      presence of neurological or nonneurological gait abnormalities. MEASUREMENTS:
      Prevalence and incidence of gait disorders based on clinical evaluations and time
      to institutionalization and death. RESULTS: Of 468 subjects (95.9%) with baseline
      gait evaluations, 168 had abnormal gaits: 70 neurological, 81 nonneurological,
      and 17 both. Prevalence of abnormal gait was 35.0% (95% confidence interval (CI)
      = 28.6-42.1). Incidence of abnormal gait was 168.6 per 1,000 person-years (95% CI
      = 117.4-242.0) and increased with age. Men had a higher incidence of neurological
      gait abnormalities, whereas women had a higher incidence of nonneurological
      gaits. Abnormal gaits were associated with greater risk of institutionalization
      and death (hazard ratio (HR) = 2.2, 95% CI =1.5-3.2). The risk was strongly
      related to severity of impairment; subjects with moderate to severe gait
      abnormalities (HR = 3.2, 95% CI = 1.9-5.2) were at higher risk than those with
      mild gait abnormalities (HR = 1.8, 95% CI = 1.0-2.8). CONCLUSION: The incidence
      and prevalence of gait disorders are high in community-residing older adults and
      are associated with greater risk of institutionalization and death.

PMID- 16460377
TI  - Lower extremity physical performance and use of compensatory strategies for
      mobility.
AB  - OBJECTIVES: To compare measured lower extremity physical performance in the
      clinic with the methods used to carry out mobility tasks at home and to identify
      key factors influencing day-to-day task performance. DESIGN: Cross-sectional
      analysis of the Women's Health and Aging Study I. SETTING: Community-dwelling
      female residents of Baltimore, Maryland. PARTICIPANTS: One thousand two
      cognitively intact women aged 65 and older with moderate to severe physical
      limitations. MEASUREMENTS: Compensatory strategies reportedly used for mobility
      in the home, distinguishing between use of no compensatory strategies, behavioral
      changes only, durable medical equipment (DME) with or without behavioral change,
      and human help; measured lower extremity (LE) physical performance (gait speed,
      timed chair stands, balance). RESULTS: There was a statistically significant
      difference in LE physical performance between women using the four types of
      compensatory strategy (P < .001). Women who used DME for mobility in the home had
      worse performance than those using human help who in turn had worse performance
      than those with behavioral changes only; women reporting no compensatory
      strategies for in-home mobility performed best. Sequential multivariate logistic
      regressions identified several factors other than LE physical performance that
      were associated with use of specific compensatory strategies. Medical conditions,
      education, and environmental barriers influenced whether compensatory strategies
      were used at all, whereas income, contact with health providers, and availability
      of help in the home influenced the type of compensatory strategy. CONCLUSION:
      Physical abilities are an important factor influencing use of compensatory
      strategies for mobility, but several other factors also influence the ways that
      women adapt to mobility limitations.

PMID- 16460378
TI  - The effect of emergency department crowding on the management of pain in older
      adults with hip fracture.
AB  - OBJECTIVES: To evaluate the effect of emergency department (ED) crowding on
      assessment and treatment of pain in older adults. DESIGN: Retrospective review of
      ED records from a prospective cohort study. SETTING: Urban, academically
      affiliated, tertiary medical center. PARTICIPANTS: One hundred fifty-eight
      patients, aged 50 and older, evaluated and hospitalized from the ED with hip
      fracture. MEASUREMENTS: Patient-related risk factors: age, sex, nursing home
      residence, ED triage status, dementia, Acute Physiology in Age and Chronic Health
      Evaluation II physiological score, and RAND comorbidity score. ED crowding risk
      factors: ED census and mean length of stay. OUTCOMES: documentation of pain
      assessment, time to pain assessment, time to pain treatment, patients reporting
      pain receiving analgesia, and meperidine use. RESULTS: Mean age was 83 (range 52
      101), 81.0% of patients complained of pain, mean time to pain assessment was 40
      minutes (range 0-600), time to treatment was 141 minutes (range 10-525), and mean
      delay to treatment was 122 minutes (range 0-526). Of those with pain, 35.9%
      received no analgesia, 7.0% received nonopioids, and 57.0% received opioids. Of
      those receiving opioids, 32.8% received meperidine. ED crowding at census levels
      greater than 120% bed capacity was significantly associated with a lower
      likelihood of documentation of pain assessment (P = .05) and longer times to pain
      assessment (P = .01). CONCLUSION: Older adults with hip fracture are at risk for
      underassessment of pain, considerable delays in analgesic administration after
      pain is identified, and treatment with inappropriate analgesics (e.g.,
      meperidine) in the ED. Higher levels of ED census are significantly associated
      with poorer pain management.

PMID- 16460379
TI  - The effects of a variant of the program for all-inclusive care of the elderly on
      hospital utilization and outcomes.
AB  - OBJECTIVES: To compare the effects of the Wisconsin Partnership Program (WPP) on
      hospital, emergency department (ED), and nursing home utilization with those of
      traditional care. DESIGN: Quasi-experimental longitudinal cohort design. SETTING:
      Selected counties in Wisconsin. PARTICIPANTS: WPP elderly enrollees and two
      matched control groups consisting of frail older people enrolled in fee-for
      service insurance plans, Medicare, and Medicaid and receiving home- and community
      based waiver services, one from the same geographic area as the WPP and another
      from a location in the state where the WPP was not offered. MEASUREMENTS: Data
      came from administrative records. Regression and survival analyses were adjusted
      for case-mix variables. RESULTS: No significant differences in hospital
      utilization, ED visits, preventable hospitalizations, risk of entry into nursing
      homes, or mortality were found. WPP enrollees had more contact with care
      providers than did controls. CONCLUSION: WPP did not dramatically alter the
      pattern of care. Part of the weak effect may be attributable to the small numbers
      of WPP cases per participating physician.

PMID- 16460380
TI  - Two outbreaks of severe respiratory disease in nursing homes associated with
      rhinovirus.
AB  - OBJECTIVES: To characterize illness and identify the etiology for two nursing
      home outbreaks of respiratory illness. DESIGN: Multisite outbreak investigations;
      cohort. SETTING: Two nursing homes in Pennsylvania. PARTICIPANTS: Facility A
      residents (n = 170), Facility B residents (n = 124), and employees (n = 91).
      MEASUREMENTS: Medical records for Facility A and B residents were reviewed, and
      employees from Facility B self-administered a questionnaire to identify risk
      factors for illness. Serological, oropharyngeal, and nasopharyngeal specimens
      were collected for both outbreaks, and testing for respiratory pathogens was
      performed. RESULTS: In Facility A, 40 (24%) of 170 residents were identified with
      respiratory illness; 13 (33%) case-patients had radiographically confirmed
      pneumonia, 15 (38%) were taken to a hospital, and two (5%) died. Of 10 specimens
      collected from symptomatic Facility A case-patients, four (40%) tested positive
      using reverse transcription polymerase chain reaction for rhinovirus. In Facility
      B, 77 (62%) of 124 residents had respiratory illness, and 40 (52%) had
      radiographically confirmed pneumonia; 12 (16%) case-patients were hospitalized,
      and five (6%) died. Of 19 respiratory specimens collected from symptomatic
      Facility B case-patients, six (32%) were positive for rhinovirus; one was from an
      employee. Five (50%) of 10 rhinovirus-positive cases in both outbreaks had
      clinical and radiographic evidence of pneumonia. CONCLUSION: These investigations
      suggest that rhinoviruses may be an underrecognized cause of respiratory
      outbreaks in nursing homes, capable of causing pneumonia and perhaps death.

PMID- 16460381
TI  - Occurrence and treatment of suspected pneumonia in long-term care residents dying
      with advanced dementia.
AB  - OBJECTIVES: To describe the occurrence and management of suspected pneumonia in
      end-stage dementia and to identify factors associated with aggressiveness of
      antibiotic treatment. DESIGN: Retrospective cohort study. SETTING: A 675-bed long
      term-care facility in Boston, Massachusetts. PARTICIPANTS: Two hundred forty
      subjects aged 65 and older who died with advanced dementia between January 2001
      and December 2003. Subjects who had suspected pneumonia during the last 6 months
      of life were identified. MEASUREMENTS: Independent variables included subject
      characteristics and features of suspected pneumonia episodes. These variables
      were obtained from medical records. Antibiotic treatment for each episode was
      determined. Multivariate analysis was used to identify independent variables
      associated with aggressiveness of treatment. RESULTS: One hundred fifty-four
      (64%) subjects with advanced dementia experienced 229 suspected pneumonia
      episodes during the last 6 months of life. Within 30 days of death, 53% of
      subjects had suspected pneumonia. Antibiotic treatment for the 229 episodes was
      as follows: none, 9%; oral only, 37%; intramuscular, 25%; and intravenous, 29%.
      Factors independently associated with more-invasive therapy were lack of a do-not
      hospitalize order (adjusted odds ratio (AOR) = 3.24, 95% confidence interval (CI)
      = 2.02-5.22), aspiration (AOR = 2.75, 95% CI = 1.44-5.26), primary language not
      English (AOR = 2.21, 95% CI = 1.17-4.15), and unstable vital signs (AOR = 2.02,
      95% CI = 1.10-3.72). CONCLUSION: Pneumonia is a common terminal event in advanced
      dementia for which many patients receive parenteral antibiotics. The
      aggressiveness of treatment is most strongly determined by advance care planning,
      the patient's cultural background, and clinical features of the suspected
      pneumonia episode.

PMID- 16460382
TI  - Differences in the features of aspiration pneumonia according to site of
      acquisition: community or continuing care facility.
AB  - OBJECTIVES: To determine the prevalence of aspiration pneumonia and to compare
      the features and risk factors for this entity in patients from continuing care
      facilities (CCFs) and the community who were admitted to the hospital with
      pneumonia. DESIGN: Prospective population-based study. SETTING: Six hospitals in
      Capital Health Region (Edmonton), Alberta, Canada. PARTICIPANTS: One thousand
      nine hundred forty-six adults admitted with pneumonia. Patients were stratified
      by their residence as community or CCF. MEASUREMENTS: Aspiration pneumonia
      prevalence; risk factors; and outcomes such as mortality, length of stay, and
      intensive care unit admission rates. RESULTS: Ten percent of those with community
      acquired pneumonia (CAP) had aspirated, compared with 30% of those with CCF
      acquired pneumonia. Those with community-acquired aspiration pneumonia (CAAP) and
      those with CCF-acquired aspiration pneumonia (CCF-AP) were younger, more likely
      to go to ICU, and more likely to require mechanical ventilation and had a longer
      length of stay and a higher mortality rate than nonaspirators. The risk factors
      for aspiration differed; for those with CAAP, impaired consciousness due to
      alcohol, drugs, or hepatic failure predominated, whereas 72% of those with CCF-AP
      had neurological disease that resulted in dysphagia. Eighty percent were treated
      with antibiotics effective against anaerobic bacteria. CONCLUSION: Aspiration
      pneumonia is common in patients with both CAP and CCF-acquired pneumonia. The
      risk factors differ, and there is a high mortality rate. Neurological disease
      dominates as the predisposing factor toward aspiration pneumonia in people in
      CCFs.

PMID- 16460383
TI  - Factors associated with vaccination of medicare beneficiaries in five U.S.
      communities: Results from the racial and ethnic adult disparities in immunization
      initiative survey, 2003.
AB  - OBJECTIVES: To examine vaccination in seniors in the five U.S. communities of the
      Racial and Ethnic Adult Disparities in Immunization Initiative. DESIGN: Cross
      sectional telephone survey in spring 2003 using stratified sampling by ZIP code
      and race/ethnicity. SETTING: New York, Texas, Wisconsin, Illinois, and
      Mississippi. PARTICIPANTS: Four thousand five hundred seventy-seven Medicare
      beneficiaries. MEASUREMENTS: Outcomes were pneumococcal vaccination ever and
      influenza vaccination in 2002/03 and were determined according to race/ethnicity,
      awareness of vaccination, and provider recommendation. Survey questions also
      asked about future plans for vaccination, whether respondents believed they had
      become sick from prior influenza vaccination, and whether unvaccinated
      respondents would be vaccinated if a health professional recommended it. RESULTS:
      Pneumococcal vaccination coverage was 70.3% for whites, 40.8% for blacks, and
      53.2% for Hispanics, and the proportion reporting provider recommendation for
      vaccination differed significantly according to race/ethnicity. In multivariate
      regression, provider recommendation (risk ratio (RR) = 2.32, 95% confidence
      intervals (CI) = 2.10-2.57) and awareness of vaccination (RR = 1.60, 95% CI =
      1.40-1.82) were associated with greater pneumococcal vaccination. Influenza
      vaccination coverage was 76.2% for whites, 50.7% for blacks, and 65.7% for
      Hispanics. A little more than half of respondents reported provider
      recommendation for influenza vaccination, with no differences according to
      race/ethnicity. Provider recommendation was associated with influenza vaccination
      (RR = 1.31, 95% CI = 1.25-1.38). More blacks and Hispanics believed they had
      become sick from prior influenza vaccination than whites, and this belief was
      associated with lower vaccination rates. CONCLUSION: This survey details
      vaccination patterns in an ethnically and geographically diverse sample of
      seniors and identifies some differences between blacks, Hispanics, and whites
      that may contribute to disparities in vaccination coverage. Survey findings
      highlight the importance of provider vaccination recommendations.

PMID- 16460384
TI  - Effect of a dementia care management intervention on primary care provider
      knowledge, attitudes, and perceptions of quality of care.
AB  - OBJECTIVES: To evaluate the effect of a multicomponent dementia care management
      program on primary care provider knowledge, attitudes, and perceptions of quality
      of dementia care. DESIGN: A clinic-level randomized, controlled trial of a
      comprehensive care management program for patients with dementia and their
      nonprofessional caregivers. The program included provider education and protocols
      for care managers to communicate with patients' medical providers. SETTING:
      Eighteen clinics (nine intervention, nine [corrected] usual care) in three
      healthcare systems in San Diego, California. PARTICIPANTS: Two hundred thirty-two
      medical providers; 129 from nine [corrected] intervention clinics; 103 from nine
      [corrected] usual-care clinics. MEASUREMENTS: Providers were surveyed 9 months
      after intervention onset on knowledge (five items on four topics), attitudes
      about dementia (three items), and perception of quality of dementia care in their
      practice setting (three items). Multivariable linear and logistic regression
      models were used to evaluate the differences between intervention and usual-care
      providers, adjusting for covariate effects across groups and clustering by
      clinic. RESULTS: One hundred sixty-six of 232 (72%) providers responded.
      Intervention providers had better knowledge about assessing decision-making
      capacity than usual-care providers (adjusted difference in percentage correct =
      12%; adjusted odds ratio = 2.4, 95% confidence interval = 1.2-4.8). Intervention
      providers viewed dementia patients as more difficult to manage in primary care
      than usual-care providers (P = .03). There were no other differences in
      knowledge, attitudes, or care quality perceptions across intervention and usual
      care providers. CONCLUSION: A comprehensive dementia care management model
      resulted in few differences in provider knowledge or attitudes favorable to
      dementia care, suggesting that this care model's effects on quality were
      primarily mediated through other components of the care management program.

PMID- 16460385
TI  - Risk and predictors of motor-performance decline in a normally functioning
      population-based sample of elderly subjects: the Italian Longitudinal Study on
      Aging.
AB  - OBJECTIVES: To examine risk and predictors of motor-performance (MP) decline
      targeting subjects performing normally at an initial observation. DESIGN: Cohort
      study. SETTING: A subsample of the Italian Longitudinal Study on Aging (aged 65
      84). PARTICIPANTS: One thousand fifty-two subjects (mean age+/-standard deviation
      = 71+/-5, 69% men) with normal MP at baseline. MEASUREMENTS: Six tests (standing
      up from a chair, stepping up, tandem walk, standing on one leg, walking speed,
      and steps turning 180 degrees ) were used to assess MP at baseline and after 3
      years. Baseline characteristics were potential predictors of MP decline. RESULTS:
      Of the 1,052 subjects performing normally at baseline, 166 (15.8%) had declined
      in MP at follow-up. Older age, female sex, lower education, symptoms of distal
      symmetrical neuropathy, cognitive impairment without dementia, parkinsonism,
      heart failure, anemia, depressive symptoms, worse Mini-Mental State Examination
      score, and lost activities of daily living and instrumental activities of daily
      living (IADLs) were significantly associated with MP decline in univariate
      comparisons. Older age (odds ratio (OR) = 3.84, 95% confidence interval (CI) =
      2.14-6.88 comparing age classes > or =80 with 65-69), female sex (OR=1.50, 95% CI
      = 1.03-2.20), distal symmetric neuropathy (OR = 2.00, 95% CI = 1.03-3.87),
      depressive symptoms (OR = 1.85, 95% CI = 1.17-2.24), and baseline IADLs (OR =
      1.22, 95% CI = 1.08-1.37 for each lost activity) independently predicted MP
      decline after regression analysis. CONCLUSION: In a population-based cohort of
      elderly people with normal MP, one-sixth declined in 3 years. Age, sex, distal
      symmetrical neuropathy, depressive symptoms, and baseline IADLs independently
      predicted this decline. Distal symmetrical neuropathy is underestimated in the
      clinical and epidemiological evaluation of motor decline in older people.

PMID- 16460386
TI  - Global sleep satisfaction of older people: the Jerusalem Cohort Study.
AB  - OBJECTIVES: To describe the nature of global sleep satisfaction (GSS) of older
      people and the factors associated with it. DESIGN: A 7-year follow-up of an age
      homogenous cohort. SETTING: Community based. PARTICIPANTS: Two hundred ninety
      subjects aged 70 at baseline and 77 at follow-up. MEASUREMENTS: Self-reported
      sleep domains and a comprehensive assessment of health variables, including
      psychosocial, physical, and functional factors, at ages 70 and 77. RESULTS: GSS
      was found to be poor in 25% of subjects at ages 70 and 77, with an estimated
      average annual remission rate of 7% and an annual incidence of 2.4%. Poor GSS at
      ages 70 and 77 was significantly associated with difficulty falling asleep,
      awakening feeling tired, two or more nocturnal awakenings, and taking sleeping
      tablets. Significant cross-sectional associations were found at age 70 and 77
      between poor GSS and poor self-rated health, general fatigue, depression,
      dependence in one or more activities of daily living, and low level of physical
      activity. In a regression analysis, risk factors at age 70 for subsequent poor
      GSS were loneliness, depression, poor self-rated health, economic difficulties,
      back pain, obesity, and prior poor GSS. The only significant long-term
      association was between poor GSS and poor self-rated health. GSS did not
      influence mortality data. CONCLUSION: Poor GSS in older people is common and
      chronic. Its chief determinants are loneliness, depression, poor self-rated
      health, economic difficulties, back pain, and obesity. It predicts poor self
      rated health but not increased mortality.

PMID- 16460387
TI  - Morbidity and older persons' perceptions of the quality of their primary care.
AB  - OBJECTIVES: To quantify the association between community-dwelling older persons'
      level of morbidity and their perceptions of the quality of their primary care.
      DESIGN: Cross-sectional study. SETTING: Urban primary care practice.
      PARTICIPANTS: A sample of community-dwelling members of a capitated health plan
      aged 65 and older who were patients of four general internists in one urban
      practice (N = 120). MEASUREMENTS: The Johns Hopkins Adjusted Clinical Groups case
      mix system was used to designate a person's aggregate morbidity level as moderate
      or high depending on the number and types of chronic conditions they had. Aspects
      of quality of primary care (physician-patient communication, interpersonal
      treatment, knowledge of patient, integration of care, and trust in physician)
      were assessed using the Primary Care Assessment Survey. RESULTS: All participants
      were classified as having moderate (41%) or high morbidity (59%). Older adults
      with high morbidity assigned a lower rating to all aspects of quality of primary
      care (physician-patient communication (P = .001), interpersonal treatment (P =
      .002), knowledge of patient (P = .03), integration of care (P = .004), and trust
      in physician (P = .01)) than those with moderate morbidity. The differences in
      quality of primary care remained statistically significant after controlling for
      age, sex, race, and education level. CONCLUSION: Older persons with multiple
      chronic conditions report inadequate quality of primary care and dissatisfaction
      with their care. Those with high morbidity levels experience poorer quality of
      primary care than those with moderate morbidity in all five aspects measured
      here.

PMID- 16460388
TI  - Memory complaint is not necessary for diagnosis of mild cognitive impairment and
      does not predict 10-year trajectories of functional disability, word recall, or
      short portable mental status questionnaire limitations.
AB  - OBJECTIVES: To evaluate the prevalence and utility of memory complaint in a
      geographically representative cohort and, in cases with mild cognitive impairment
      (MCI), to determine whether memory complaint alters 10-year trajectories of
      disability in activities of daily living (ADLs), Short Portable Mental Status
      Questionnaire (SPMSQ) score, and 20-item word recall. DESIGN: Prospective cohort
      study. SETTING: Washington and Iowa counties, Iowa. PARTICIPANTS: Iowa
      Established Populations for Epidemiologic Studies of the Elderly (N = 3,673; aged
      > or =65; 61.3% female; 99.9% white). MEASUREMENTS: Age, sex, education, SPMSQ
      score, 20-item word recall, ADL or instrumental ADL disability, and chronic
      medical conditions. RESULTS: The prevalence of memory complaint was 34%. Although
      proportionally more cognitively impaired individuals were in the memory complaint
      group (34% vs 27%), the pattern of subclassification into cognitively intact and
      MCI Stage 1 and 2 subgroups was similar for people with and without memory
      complaint. Median SPMSQ score and number of words recalled at baseline were
      comparable across memory complaint categories in each subgroup. MCI participants
      without subjective memory complaint constituted a larger proportion of the
      overall sample than individuals with subjective memory complaint (460 (14%) vs
      295 (8.9%)) and of persons objectively classified as having MCI (61% vs 39%). The
      distribution of individual 10-year change in ADL disability, SPMSQ score, and
      word recall were similar for those with and without memory complaint across all
      subgroups of cognitive impairment. CONCLUSION: Memory complaint is not necessary
      for MCI diagnosis and does not distinguish cases with different progression rates
      in disability or cognitive impairment. 2006.

PMID- 16460389
TI  - Rates of acute care admissions for frail older people living with met versus
      unmet activity of daily living needs.
AB  - OBJECTIVES: To determine whether older people who do not have help for their
      activity of daily living (ADL) disabilities are at higher risk for acute care
      admissions and whether entry into a program that provides for these needs
      decreases this risk. DESIGN: A longitudinal cohort study. SETTING: Thirteen
      nationwide sites for the Program of All-inclusive Care for the Elderly (PACE).
      PACE provides comprehensive medical and long-term care to community-living older
      adults. PARTICIPANTS: Two thousand nine hundred forty-three PACE enrollees with
      one or more ADL dependencies. MEASUREMENTS: Unmet needs were defined as the
      absence of paid or unpaid assistance for ADL disabilities before PACE enrollment.
      Hospital admissions in the 6 months before PACE enrollment and acute admissions
      in the first 6 weeks and the 7th through 12th weeks after enrollment were
      determined. RESULTS: Those who lived with unmet ADL needs before enrollment were
      more likely to have a hospital admission before PACE enrollment (odds ratio (OR)
      = 1.28, 95% confidence interval (CI) = 1.01-1.63) and an acute admission in the
      first 6 weeks after enrollment (OR = 1.45, 95% CI = 1.00-2.09) but not after 6
      weeks of receiving PACE services (OR = 0.86, 95% CI = 0.53-1.40). CONCLUSION:
      Frail older people who live without needed help for their ADL disabilities have
      higher rates of admissions while they are living with unmet ADL needs but not
      after their needs are met. With state governments under increasing pressure to
      develop fiscally feasible solutions for caring for disabled older people, it is
      important that they be aware of the potential health consequences of older adults
      living without needed ADL assistance.

PMID- 16460390
TI  - Hyponatremia and arginine vasopressin dysregulation: mechanisms, clinical
      consequences, and management.
AB  - Hyponatremia, the most common electrolyte disorder, occurs frequently in older
      people and in hospitalized patients. Physiological changes of aging that interact
      with diseases and drugs commonly present in older people put this population at
      greater risk for hyponatremia. It can accompany central nervous system disorders,
      pulmonary and renal disease, cancer, congestive heart failure, and liver
      cirrhosis, as well as many commonly used drugs. Delayed recognition can lead to
      symptomatic hyponatremia with consequent cerebral edema and possibly irreversible
      neurological damage. Symptoms and signs of hyponatremia may be subtle or not
      attributed to hyponatremia. Most cases are of the euvolemic type, in which
      extracellular fluid volume is normal and is often due to the syndrome of
      inappropriate secretion of antidiuretic hormone. Hyponatremia can also occur in
      association with hypervolemia or hypovolemia. Common to all of these
      circumstances is increased secretion of arginine vasopressin (AVP). Understanding
      of the pathophysiological basis of hyponatremia and of brain compensatory
      mechanisms is critical to safe treatment. Fluid restriction or infusion of
      hypertonic saline can improve symptoms and normalize serum sodium levels but does
      not address excess AVP, which in most cases is the underlying cause of the
      disorder. A major new approach to treatment of hyponatremia is the development of
      aquaretics: AVP-receptor antagonists that provide a targeted therapeutic approach
      to correcting the many kinds of hyponatremia caused by excess AVP levels.

PMID- 16460391
TI  - A systematic review of the efficacy and safety of atypical antipsychotics in
      patients with psychological and behavioral symptoms of dementia.
AB  - Although the Food and Drug Administration (FDA) has not approved atypical
      antipsychotics for use in patients with dementia, they are commonly prescribed in
      this population. Recent concerns about increased risk of cerebrovascular events
      and mortality have led to warnings. A systematic review was conducted to assess
      the benefits and harms of atypical antipsychotics when used in patients with
      behavioral and psychological symptoms of dementia. Electronic searches (through
      March 2005) of the Cochrane Library, Medline, Embase, and PsycINFO were
      supplemented with hand searches of reference lists, dossiers submitted by
      pharmaceutical companies, and a review of the FDA Website and industry-sponsored
      results database. Using predetermined criteria, each study was assessed for
      inclusion, and data about study design, population, interventions, and outcomes
      were abstracted. An overall quality rating (good, fair, or poor) was assigned
      based on internal validity. The evidence for olanzapine and risperidone supports
      their effectiveness compared with placebo. Short-term adverse events were similar
      to placebo. Risperidone had no advantage over haloperidol on efficacy measures in
      the better-quality studies. Risperidone had an advantage over haloperidol on some
      measures of extrapyramidal symptoms. Evidence for the other atypical
      antipsychotics is too limited to assess efficacy and safety. Trials were short
      term and conducted in highly selected populations. The potential for increased
      risk of cerebrovascular adverse events and mortality is a serious concern. To
      make judgments about when the benefits of atypical antipsychotics outweigh the
      potential harms, clinicians need more information. Additional data from existing
      trials and more-complete reporting of trial results could provide this
      information.

PMID- 16460392
TI  - Studies of respiratory tract infection in nursing home residents: what are we
      learning?

PMID- 16460396
TI  - Brain natriuretic peptide in heart failure.

PMID- 16460394
TI  - An elderly woman with asthma and eosinophilia presenting with fluctuating
      hoarseness and laryngopyocele.

PMID- 16460397
TI  - When vitamin deficiency mimics thrombotic thrombocytopenic purpura.

PMID- 16460398
TI  - Utility of a patient-response screening question for visual impairment.

PMID- 16460399
TI  - Treatment of elderly cancer patients: a planet in evolution.

PMID- 16460400
TI  - Arterial carboxyhemoglobin concentrations as a predictor of chemosensitivity in
      elderly patients with advanced lung cancer.

PMID- 16460401
TI  - Evidence-based prescribing of antiresorptive therapy for female nursing home
      residents with osteoporosis: how good is the evidence?

PMID- 16460402
TI  - The accuracy of the Mini-Cog in screening low-educated elderly for dementia.

PMID- 16460404
TI  - Outcomes of older people admitted to postacute facilities with delirium.

PMID- 16460403
TI  - Carbocisteine reduces frequency of common colds and exacerbations in patients
      with chronic obstructive pulmonary disease.

PMID- 16460406
TI  - Self-efficacy and fear of falling: in search of complete theory.

PMID- 16460407
TI  - Facts about atypical antipsychotics.

PMID- 16460408
TI  - Healthcare ergonomics, part 2.

PMID- 16460409
TI  - Fractured penis.
AB  - PURPOSE: To provide nurse practitioners (NP) with information concerning the
      uncommon occurrence of penile fracture, a review of the anatomy and physiology of
      the penile shaft, signs and symptoms to be included in assessment, diagnostic
      tests, treatment, and referral are discussed. DATA SOURCES: Current literature
      available in journals and textbook, and clinical experience. CONCLUSIONS: Penile
      fracture, although an uncommon incident, is an urgent condition that requires a
      urology consult and surgical repair. IMPLICATIONS FOR PRACTICE: Because of the
      serious nature of this injury and the potential for complications, NPs need to
      obtain an urgent urology consult when penile fracture is suspected or diagnosed.
      The characteristic typical clinical presentation usually eliminates the need for
      expensive or invasive tests for diagnosis.

PMID- 16460410
TI  - Syphilis: an old enemy still lurks.
AB  - PURPOSE: To review the problem of increasing cases of syphilis as a communicable
      disease and to review different presentations of syphilis and to discuss
      treatment guidelines. DATA SOURCES: Extensive review of worldwide scientific
      literature on the epidemiology, diagnosis, and treatment of syphilis.
      CONCLUSIONS: Syphilis is an infectious sexually transmitted disease, which may
      have devastating consequences. Previously declining rates have led to complacency
      in prevention and diagnosis. Primary prevention includes education regarding
      safer sexual practices. Secondary prevention includes early identification via
      screening and treatment. IMPLICATIONS FOR PRACTICE: Syphilis is a contagious
      disease that has devastating consequences if not diagnosed and treated. Providers
      should keep ever vigilant in its identification. Specifically, it should be
      considered when evaluating all symptom-less dermatological lesions.

PMID- 16460411
TI  - Mentoring--a complex relationship.
AB  - PURPOSE: To address the process of mentoring the advanced practice nurse (APN)
      and provide suggestions for the formulation, implementation, and termination of
      the relationship. DATA SOURCES: Research studies from nursing as well as other
      disciplines and personal experience as a mentor and protege. CONCLUSIONS:
      Mentoring is a dynamic and complex relationship that can support growth, increase
      synergy, and develop ways to succeed as an APN. Before entering into the
      relationship, care should be taken to assure compatibility between the mentor and
      the protege. Major pitfalls include poor communication patterns and inadequate
      identification of objectives. Keys for repair or termination of the relationship
      include personal introspection, honest and nonblaming communication, and
      development of alternative support networks. IMPLICATIONS FOR PRACTICE:
      Successful mentoring relationships improve professional growth, competency, and
      productivity. They also form the basis for ongoing preparation of a new
      generation of APNs.

PMID- 16460412
TI  - A survey of female nursing students' knowledge, health beliefs, perceptions of
      risk, and risk behaviors regarding human papillomavirus and cervical cancer.
AB  - PURPOSE: The purpose of the study was to assess knowledge of, perceived
      susceptibility to, perceived seriousness of, and risk behaviors regarding human
      papillomavirus (HPV) and cervical cancer among female nursing students. DATA
      SOURCES: A 40-item survey of HPV and cervical cancer was distributed to a
      convenience sample of 240 female nursing students enrolled in a baccalaureate
      nursing program. CONCLUSIONS: Female nursing students participate in high-risk
      sexual behaviors and have a fairly low knowledge level, low perceived
      susceptibility, and low perceived seriousness regarding HPV and cervical cancer.
      Knowledge and perceived susceptibility were positively related to number of
      sexual partners. This may indicate that the women who engage in riskier behavior
      are more knowledgeable about HPV and their risk of contracting the disease.
      IMPLICATIONS FOR PRACTICE: Results indicate that all practitioners involved in
      the care of women should educate them about HPV and its relationship to cervical
      cancer. Education should include the need to use condoms to prevent HPV and other
      sexually transmitted diseases.

PMID- 16460413
TI  - Childhood obesity: prevention practices of nurse practitioners.
AB  - PURPOSE: The purposes or this study were to (a) describe the prevention practices
      of nurse practitioners (NPs) regarding childhood obesity, (b) compare the
      practices of NPs by specialty, practice setting, and awareness of childhood
      obesity prevention guidelines, (c) identify relationships between prevention
      practices and demographic variables of NPs, and (d) examine the resources for and
      barriers to implementing prevention practices. DATA SOURCES: A convenience sample
      of 99 family NPs (FNPs) and pediatric NPs (PNPs) from the Intermountain area was
      used. Participants completed a questionnaire based on documented risk factors for
      childhood obesity as well as prevention guidelines developed by the American
      Academy of Pediatrics (AAP). CONCLUSIONS: NPs working in family practice or
      general pediatric practice settings were not consistently using the BMI-for-age
      index to screen for childhood obesity, as recommended by the AAP. However, they
      were teaching parents to promote healthy food choices and physical activity in
      their families. PNPs and FNPs working in a pediatric practice setting and NPs who
      were aware of prevention guidelines were more likely to perform several
      prevention strategies than FNPs working in a family practice setting and those
      who were unaware of guidelines. Major barriers to implementing childhood obesity
      prevention strategies included parental attitudes, the American lifestyle, and
      lack of resources for both the NP and the family. The main resources NPs used in
      preventing childhood obesity were a dietician, journal articles, and Web sites.
      IMPLICATIONS FOR PRACTICE: Although the majority of the NPs in this study
      reported being aware of childhood obesity prevention guidelines (73.7%), most
      were not consistently using BMI for age or monitoring children at increased risk
      for obesity. Because childhood obesity is escalating at such a rapid rate, it is
      critical that NPs working in family practice and pediatric practice settings take
      the necessary steps to help curtail obesity in childhood, including calculating
      BMI for age, targeting children at risk, and helping families develop healthy
      nutrition and physical activity habits. In addition to proper health supervision
      of children, NPs also need to be advocates in their communities to overcome
      barriers to childhood obesity prevention.

PMID- 16460414
TI  - Teaching with an eye on the storm.

PMID- 16460415
TI  - Racial differences in parenting dimensions and adolescent condom use at sexual
      debut.
AB  - OBJECTIVES: Parenting style may be a determinant in reducing adolescent risk
      behavior. Previous studies have relied on a typological parenting approach, with
      classification into four groups: authoritative, authoritarian, permissive, and
      neglectful. In this study, two distinct parenting dimensions, demandingness and
      responsiveness, were examined as independent predictors of adolescent condom use.
      DESIGN AND SAMPLE: This study used a subsample of the National Longitudinal Study
      of Adolescent Health (Add Health) that included 153 adolescent-mother pairs.
      MEASUREMENT: Maternal demandingness and responsiveness were measured using Wave I
      mother interviews. Logistic regression analyses were used to predict adolescent
      condom use at sexual debut at Wave II and to assess moderation by gender and
      race. RESULTS: (1) Maternal demandingness predicted increased likelihood of
      condom use in African American adolescents but decreased likelihood of condom use
      in White adolescents; (2) maternal responsiveness did not predict condom use; and
      (3) gender moderation was not present. CONCLUSIONS: To provide appropriate family
      counseling, public health nurses need to consider racial differences in
      contraceptive practices. Education regarding parental supervision practices
      should be considered as part of nursing interventions intended to increase condom
      use in African American adolescents.

PMID- 16460416
TI  - Profiles of self-reported HIV-risk behaviors among injection drug users in
      methadone maintenance treatment, detoxification, and needle exchange programs.
AB  - OBJECTIVE: Injection drug use has accounted for more than one third of acquired
      immune deficiency syndrome cases in the United States. The purpose of this study
      was to compare the demographic characteristics, types, and frequency of human
      immunodeficiency virus (HIV)-risk behaviors among injection drug users (IDUs)
      recruited from a needle exchange program (NEP), methadone maintenance treatment
      (MMT), and detoxification (detox) program. DESIGN: A cross-sectional,
      correlational design was used to determine whether the selected HIV-risk
      behaviors and demographic characteristics of IDUs varied by site of recruitment.
      SAMPLE AND MEASUREMENTS: Confidential questionnaires were completed by 445 IDUs
      in Philadelphia, Pennsylvania. RESULTS: Data analysis revealed that HIV sexual
      and injection-risk behavior varied by recruitment site. Subjects recruited from
      the NEP were more likely to engage in HIV-risk behaviors than subjects recruited
      from the MMT or detox sites. CONCLUSIONS: Interventions occurring in program and
      treatment sites need to be sensitive to various demographic characteristics and
      behaviors if they are to reach those at highest risk of HIV infection. Targeting
      HIV prevention interventions based upon risk group membership alone (e.g. IDUs)
      fails to address the distinct risk behaviors and demographic characteristics of
      enrollees in different programs.

PMID- 16460417
TI  - A qualitative approach to understanding patients' diagnosis of Lyme disease.
AB  - OBJECTIVES: The purpose of this study was to explore the lived experience of
      becoming diagnosed with Lyme disease. DESIGN: A qualitative, phenomenological
      study was conducted to investigate the experience of becoming diagnosed with Lyme
      disease. SAMPLE: A purposive sample of 10 participants diagnosed with Lyme
      disease were interviewed and tape-recorded. Data saturation guided the size of
      the sample. METHODS: The interviews were transcribed verbatim. Key words or
      phrases were extracted and clustered; clusters were interpreted into themes.
      Analyzed data were confirmed with the participants for trustworthiness and
      reliability. RESULTS: Six themes emerged from the interviews. Participants
      expressed feelings of frustration during the long road to diagnosis. They endured
      multiple diagnostic tests and were seen by numerous health care providers.
      Participants voiced financial stress. They expressed the need for self-advocacy
      and felt validation when a diagnosis was made. Despite the chronicity of their
      illness, the participants voiced a sense of hopefulness for their future.
      CONCLUSION: A deep understanding of the lived experience of becoming diagnosed
      with Lyme disease allows for nurses to prioritize health care interventions and
      strategize ways to implement quality improvement systems as clients enter the
      health care environment.

PMID- 16460418
TI  - Talking circles: Northern Plains tribes American Indian women's views of cancer
      as a health issue.
AB  - OBJECTIVE: The purpose of this research was to understand the cultural meanings
      of cancer among American Indian women from Northern Plains tribes living in
      western South Dakota and their experiential view of breast and cervical cancer
      screening. DESIGN AND SAMPLE: Using an exploratory design, a purposive sample of
      28 women, 35-75 years of age, were recruited into three Talking Circles.
      MEASUREMENT: Talking Circle and focus group methodology, combined with Affonso's
      Focus Groups Analytic Schema, were used to generate contextual data sets
      including thematic findings. RESULTS: Ten themes emerged indicating
      interrelationships between cultural traditions and health structures of care. The
      themes provided a unique perspective for conceptualizing women's experiences with
      breast and cervical cancer screening. CONCLUSIONS: Incorporating women's cultural
      experiences into screening services is necessary to address clinical and policy
      challenges for reducing breast and cervical cancer mortality among American
      Indian women. Findings from this research will be used to guide a future study
      investigating breast-screening patterns related to mammography adherence and
      development of interventions specific to American Indian women.

PMID- 16460419
TI  - The health promotion of aging workers from the perspective of occupational health
      professionals.
AB  - OBJECTIVES: This study defines and describes, from the perspective of
      occupational health professionals, (a) the aging worker, (b) health promotion for
      aging workers, (3) employees' health-promoting activities, (4) workplace health
      promotion factors, (5) occupational health promotion activities, (6) co-partners
      supporting the health promotion, and (7) the impact of health promotion
      activities for older workers. A model is proposed, based on these issues. DESIGN:
      A cross-sectional, qualitative design was used to analyze e-mailed essays.
      Content analysis of the essays yielded themes that were validated by an
      independent research colleague. SAMPLE: Ten group essays from 16 occupational
      health professionals who had participated in the Health Promotion Project of
      Aging Workers in Northern Karelia, Finland were received. RESULTS: An aging
      employee was defined as a mature worker. Health promotion was defined as early
      prevention of the influence of health hazards. Workers can improve their health
      through living habits, positive attitude, personal relationships, and education.
      Individual work arrangements, good work atmosphere, and appreciative leadership
      were essential factors for the health of workers. Occupational health
      professionals supported workers by health examinations, workplace visits,
      counseling, and organizing activities. CONCLUSIONS: The impacts of health
      promotion activities were better health, productivity, and work satisfaction.

PMID- 16460420
TI  - Fathers clubs to improve child health in rural Haiti.
AB  - OBJECTIVES: This paper describes an innovative public health nursing strategy,
      village-based fathers clubs, to improve child and family health in rural Haiti.
      It discusses related nursing implications in Haiti and other parts of the world.
      DESIGN: Relevant current literature was reviewed and evaluated with respect to
      child health in Haiti and the development of the fathers clubs. Program
      participants and organizers were consulted. SAMPLE: The fathers clubs in remote
      areas of Jeremie Haiti, participants and program directors, provided input for
      this description. RESULTS: Public health practitioners continually face grave
      challenges when addressing the health care needs in less developed countries. One
      such case is Haiti, where crushing poverty, poor infrastructure, a failing
      economy, natural disasters, and chaotic sociopolitical conditions compound these
      challenges. Public health practitioners, including nurses, must seek creative,
      culturally-appropriate, low technologic approaches to improve the health of the
      children and families in the remote villages of Haiti. The institution and
      support of village fathers clubs is one approach that has been ongoing since
      1994. Fathers meet together on a regular basis for health education, support, and
      community building activities. The curriculum is health-based and facilitated by
      nurses, with participation by young and old men alike. CONCLUSIONS: Participants
      and organizers believe that family and child health is improved as a result of
      the groups.

PMID- 16460421
TI  - Needs assessment and intervention strategies to reduce lead-poisoning risk among
      low-income Ohio toddlers.
AB  - OBJECTIVE: Examine parental receipt of lead-poisoning prevention information and
      preferred methods of receiving this information. DESIGN: Cross-sectional mailed
      survey of parents with children 1-2-year-old-enrolled in Medicaid. SAMPLE:
      Respondents (n=532) were primarily female, white, with at least a high school
      education, and between the ages of 20-30 years. MEASUREMENTS: Items from the
      Blood Lead Education and Screening Tool concerning parental receipt of lead
      poisoning prevention information, persons with whom parents had discussed lead
      poisoning prevention, parental receipt of a reminder about blood lead testing,
      and parents' preferred methods of obtaining lead-poisoning prevention
      information. RESULTS: Most respondents had obtained lead-poisoning prevention
      information, but only 28% reported receiving a reminder to have their child's
      blood lead level assessed. Brochures and discussions with health care providers
      were the preferred methods of obtaining lead-poisoning prevention information.
      More minority respondents preferred receiving information via videos, billboards,
      and home visits. Younger parents preferred brochures, billboards, and speaking
      with someone at the health department or women, infants, and children
      supplemental nutrition (WIC). Most respondents identified multiple means by which
      they would like to receive lead-poisoning prevention information. CONCLUSIONS:
      Implementation of individual, community, and system-level interventions by public
      health nurses are needed for comprehensive lead-poisoning prevention education.

PMID- 16460422
TI  - Personal access to health care: a concept analysis.
AB  - The objective of this concept analysis was to formulate an operational
      definition, so that those seeking, providing, and legislating health care policy
      would share a common interpretation of the concept. A concept analysis following
      the strategy suggested by Walker and Avant was used to identify antecedents,
      attributes, and empirical referents of access to health care. Furthermore, model,
      borderline, contrary, and invented cases were described. A theoretical definition
      was derived, which will lead to a better understanding of the concept and bring
      the concept closer to measurability and readiness for an operational definition.
      Access to health care has been addressed in political campaigns, studied by
      numerous legislative committees, and purported to be in an emergency state of
      despair. However, a measurable definition of access to health care continues to
      elude providers and legislators of health care; in as much, the meaning of the
      concept varies with the user.

PMID- 16460423
TI  - A conceptual model for understanding effective coalitions involved in health
      promotion programming.
AB  - Funding agencies are increasingly focused on community coalitions as effective
      entities for promoting public health programs. Yet, there has been no conceptual
      model for understanding how effective coalition infrastructure works to
      facilitate a learning environment, wherein coalition members and leaders receive
      ongoing training and technical assistance needed to accomplish their external
      programming goals. This article presents a conceptual model for measuring the
      internal effectiveness of coalitions [Internal Coalition Outcome Hierarchy
      (ICOH)]. The ICOH model served as the basis for development of the evaluation
      instrument, Internal Coalition Effectiveness, which measures internal coalition
      effectiveness based on achievement of organizational outcomes at each of the
      model's seven hierarchical levels. The ICOH conceptual model has broad
      application for public health nurses who are frequently called on to serve as
      evaluators for community coalitions engaged in health programming. The model has
      implications for evaluators to use in teaching coalition members and leaders
      about their internal strengths and areas for improvement, so that coalitions can
      develop more effective internal structures and thereby promote long-term
      sustainability.

PMID- 16460424
TI  - Measuring community coalition effectiveness using the ICE instrument.
AB  - This article presents the development and psychometric testing of the Internal
      Coalition Effectiveness (ICE) instrument, which was based on the conceptual model
      Internal Coalition Outcome Hierarchy. Sixty-one items were derived from
      literature about successful coalitions, and the ICE instrument was tested for
      reliability and validity. A national panel of eight experts conducted content
      validity. Remaining tests involved a sample of 61 members and leaders of a large
      midwestern coalition (77% response rate, n=47). Content validity involved a two
      stage process for rigorous item development and quantification (0.88, p<0.05).
      Internal consistency was based on bivariate Pearson's correlation of 0.30-0.70
      for two-item scales and Cronbach's alpha(alpha=0.70). Construct validity was
      assessed by correlation analysis, independent Student's t tests, and informal
      coalition feedback. The final 30-item version of ICE is psychometrically sound.
      Findings were shared with the local coalition, and, in support of the
      instrument's validity, members and leaders found this information useful for
      promoting coalition sustainability by identifying internal strengths and areas
      for improvement. The ICE instrument adds to the body of literature by measuring
      critical constructs of coalition effectiveness and has significant application
      for public health nurses working as evaluators for coalitions engaged in
      community health programming.

PMID- 16460425
TI  - Self-reported physical activity validated by pedometer: a pilot study.
AB  - OBJECTIVE: The objective was to validate self-reported physical activity based on
      a daily activity record (DAR) with concurrent pedometer and 7-day physical
      activity-recall questionnaire data. DESIGN: The design was a one-group
      descriptive correlational study. SAMPLE: The sample consisted of 25 working women
      with a mean age of 39.8 years, 92% Caucasian, and 63% with a combined family
      income of 60,000 dollars or greater. MEASUREMENTS: Three instruments: (a) DAR, a
      self-reported record of moderate or higher intensity physical activities
      including household, exercise, leisure, and occupational. Metabolic equivalent
      unit (MET) scores were calculated from the self-report data, (b) 7-day physical
      activity recall, and (3) Yamax pedometers (SW-701) measured number of steps.
      RESULTS: MET scores based on the DAR (n=22) were strongly associated with both
      pedometer data (Spearman's rho=0.607, p=0.003) and 7-day physical activity-recall
      data (Spearman's rho=0.542, p=0.009). CONCLUSION: The results of this validation
      study indicated a statistically significant correlation of self-reported physical
      activity (DAR) with pedometer values and 7-day physical activity-recall data. The
      DAR may be useful for measuring physical activity in community health programs
      and in community-based research.

PMID- 16460426
TI  - O, would some power . . .
AB  - Levity is good therapy for a variety of ailments. Consultation or auditing visits
      were undoubtedly trying to staff and supervisors of public health nursing field
      offices. Elizabeth Reed, a frequent contributor of humor and feature articles to
      the original Public Health Nursing journal, was director of the Division of
      Health Information, State Board of Health, Florida when this essay was published
      in volume 44, issue 12 (1952). Reed asserted that her one-min monologues were
      imaginary composites based on persons she had either known or about whom she had
      heard. In this segment, she took aim at nurse consultants. While the organization
      of services may have changed dramatically in the last 54 years, the personalities
      are perennially recognizable.

PMID- 16460427
TI  - Unraveling the mystery of von Willebrand factor.

PMID- 16460428
TI  - Need for randomized trials in hemophilia.

PMID- 16460429
TI  - Are randomized clinical trials the only truth? Not always.

PMID- 16460430
TI  - Can evidence harm? Certainly not hemophilia treatment and community.

PMID- 16460431
TI  - Life expectancy in hemophilia outcome.

PMID- 16460432
TI  - Mortality and causes of death in patients with hemophilia, 1992-2001: a
      prospective cohort study.
AB  - BACKGROUND: Clotting factor products have been safe for HIV since 1985, and for
      hepatitis C since 1992. Few studies have reported on mortality in the total
      population of hemophilia patients after the period of risk of viral infection
      transmission. OBJECTIVES: We studied the mortality, causes of death, and life
      expectancy of hemophilia patients between 1992 and 2001. We compared these
      findings with those of previous cohorts, together spanning the periods before,
      during, and after the use of potentially contaminated clotting products. PATIENTS
      AND METHODS: We performed a prospective cohort study among 967 patients with
      hemophilia A and B. Death rates, overall and cause-specific, were compared with
      national mortality figures for males adjusted for age and calendar period as
      standardized mortality ratio (SMRs). RESULTS: Between 1992 and 2001, 94 (9.7%)
      patients had died and two patients were lost to follow-up (0.2%). Mortality was
      2.3-times higher in hemophilia patients than in the general male population (SMR
      2.3 95% confidence interval 1.9-2.8). In patients with severe hemophilia, life
      expectancy decreased from 63 (1972-1985) to 59 years (1992-2001). Exclusion of
      virus-related deaths resulted in a life expectancy at birth of 72 years.
      CONCLUSIONS: AIDS was the main cause of death (26%) and 22% of deaths were
      because of hepatitis C. In patients not affected by viral infections, there still
      appeared to be a trend toward a moderately increased mortality compared with the
      Dutch male population. Thus, mortality of patients with hemophilia is still
      increased; this is largely because of the consequences of viral infections.

PMID- 16460433
TI  - Coagulation and metastasis--an unexpected role for von Willebrand factor.

PMID- 16460434
TI  - Cancer and subsequent risk of venous thromboembolism.

PMID- 16460435
TI  - Incidence of venous thrombosis in a large cohort of 66,329 cancer patients:
      results of a record linkage study.
AB  - BACKGROUND: The incidence of venous thrombosis (VT) for cancer patients is
      increased compared with patients without cancer, but estimations of the incidence
      for different types of cancer have rarely been made because of the low incidence
      of various types of cancer. Large registries offer an opportunity to study the
      risk of VT in large cohorts of cancer patients, which is essential in decisions
      on prophylactic anti-coagulant treatment. METHODS: This cohort study estimates
      the incidence of VT in cancer patients by using record linkage of a Cancer
      Registry and an Anticoagulation Clinic database in the Netherlands. Cumulative
      incidences in patients with different types of malignancies were estimated. We
      calculated relative risks (RRs) in relation to the presence of distant metastases
      and treatment. RESULTS: Tumors of the bone, ovary, brain, and pancreas are
      associated with the highest incidence of VT (37.7, 32.6, 32.1, and 22.7/1000/0.5
      year). Patients with distant metastases had a 1.9-fold increased risk [RRadj:
      1.9; 95% confidence interval (CI): 1.6-2.3]. Chemotherapy leads to a 2.2-fold
      increased risk (RR(adj): 2.2; 95% CI: 1.8-2.7) and hormonal therapy leads to a
      1.6-fold increased risk (RRadj: 1.6; 95% CI: 1.3-2.1) compared with patients not
      using these treatment modalities. Patients with radiotherapy or surgery did not
      have an increased risk. CONCLUSIONS: We compared the overall incidences of VT in
      the first half year in our study to the risk of major bleeding as described in
      the literature. For patients with distant metastases, for several types of
      cancer, prophylactic anti-thrombotic treatment could be beneficial.

PMID- 16460436
TI  - High postclopidogrel platelet reactivity in non-ST-elevation acute coronary
      syndrome treated with stenting: a clue for adverse prognosis?

PMID- 16460437
TI  - Clinical usefulness of cardiac biomarkers in hemodynamically stable pulmonary
      embolism.

PMID- 16460438
TI  - If heparanase is the answer, what is the question?

PMID- 16460439
TI  - Heparanase neutralizes the anticoagulation properties of heparin and low
      molecular-weight heparin.
AB  - BACKGROUND: Heparanase is a mammalian endo-D-glucuronidase that cleaves heparan
      sulfate (HS) in the extracellular matrix and cell surface. It is preferentially
      expressed by cells of the immune system and tumor cells. Heparanase
      overexpression in experimental tumor models results in increased angiogenesis and
      metastasis. Heparin and low-molecular weight heparin (LMWH) inhibit HS
      degradation by heparanase. OBJECTIVE: To investigate whether heparanase cleaves
      heparin and LMWH, and elucidate its effect on blood coagulation. METHODS: Heparin
      and LMWH were incubated with recombinant heparanase and subjected to measurements
      of molecular size (size exclusion chromatography) and anticoagulant activity
      (plasma APTT-activated thromboplastin time, and anti-Xa activity). APTT was also
      measured in plasma samples of transgenic mice overexpressing heparanase, in
      comparison with control mice. RESULTS: Incubation of heparin and LMWH with
      heparanase resulted in degradation of these substrates, as revealed by a
      significant decrease in their molecular weight. This was correlated with a marked
      suppression of the anticoagulant activity of heparin and LMWH, as indicated by a
      decreased effect on APTT and anti-Xa activity, respectively, when human plasma
      was added. Transgenic mice overexpressing heparanase exhibited a significantly
      shorter APTT than control mice. CONCLUSION: Heparanase is capable of degrading
      heparin and LMWH, so that its overexpression by tumor cells may contribute to
      heparin resistance, commonly occurring in cancer patients. In view of the
      complexity of the currently available heparanase activity assays, we propose an
      indirect approach to quantify heparanase activity by measuring the decrease in
      plasma APTT or anti-Xa activity exerted by the enzyme under the defined
      conditions.

PMID- 16460440
TI  - Incidence of venous thromboembolism following major abdominal surgery: a multi
      center, prospective epidemiological study in Japan.
AB  - BACKGROUND: Venous thromboembolism (VTE) has been considered to be a rare
      surgical complication in Japan. AIM: To investigate the incidence and risk
      factors of VTE in Japanese patients undergoing major abdominal surgery. METHODS:
      A prospective, multi-center epidemiological study was conducted from December,
      2001 to August 2002 in 39 medical institutes throughout Japan. A total of 173
      patients with general (n = 128), gynecologic (n = 23), and urologic (n = 22)
      surgery were analyzed. For the diagnosis of deep vein thrombosis (DVT), bilateral
      venography was performed in all patients. Lung ventilation/perfusion scintigraphy
      was carried out in patients suspected of pulmonary thromboembolism (PTE).
      RESULTS: There were 36 patients with distal DVT (20.8%) and five patients with
      proximal DVT (2.9%). One patient was diagnosed as PTE. Overall, VTE was diagnosed
      in 42 patients (24.3%). By univariate analysis, only age (60 years or older) was
      identified as a significant risk factor in the whole study population. When
      analyzed by the stepwise multiple logistic regression model, female gender,
      operation site, age, and operation time were four risk factors found to be
      significant. The incidence of VTE was closely related to the number of risk
      factors that patients had. As many as 44% of patients with three or four risk
      factors developed VTE while those with one or two risk factors showed about a 17%
      incidence of VTE. Four patients lacking any risk factors did not develop VTE.
      CONCLUSIONS: Venous thromboembolism is common in Japanese patients undergoing
      major abdominal surgery. Pharmacologic thromboprophylaxis is considered
      essential, particularly in those patients with multiple, potential risk factors.

PMID- 16460441
TI  - A highly informative, multiplexed assay for the indirect detection of hemophilia
      A using five-linked microsatellites.
AB  - BACKGROUND: Hemophilia A is a severe bleeding disorder caused by almost 1000
      different known mutations in the F8C gene. Direct mutation analysis is sometimes
      difficult for this disorder. When a mutation cannot be found, linkage analysis
      can be used for prenatal and carrier diagnosis. AIM: To develop a rapid and
      effective system for carrier detection and prenatal diagnosis of hemophilia A
      based on a single-multiplexed polymerase chain reaction (PCR) reaction utilizing
      five microsatellite markers. PATIENTS AND METHODS: Two intronic microsatellites
      and three other markers flanking the factor VIII gene were ascertained, and
      primers were designed for multiplex PCR amplification. A kindred with Hemophilia
      A was tested for linkage using the panel of primers, and informativity in the
      general population was ascertained by testing 50 unrelated females. RESULTS: Co
      amplification of all microsatellites was optimized using DNA extracted by
      standard methods. Rapid detection and sizing of products were carried out using
      an automated DNA sequencer. The combined microsatellite panel was informative in
      each of the kindreds tested, and in 100% of the 50 unrelated females (95% CI 94.2
      100%). CONCLUSIONS: This method enables the indirect detection of hemophilia A
      for patients in whom mutations cannot be found, facilitating carrier testing and
      prenatal analysis. It is rapid and straightforward compared with many other
      published protocols, and offers a high degree of informativity.

PMID- 16460442
TI  - Int22h-related inversions causing hemophilia A: a novel insight into their origin
      and a new more discriminant PCR test for their detection.
AB  - BACKGROUND: Intrachromosomal, homologous recombination of the duplicon int22h-1
      with int22h-2 or int22h-3 causes inversions accounting for 45% of severe
      hemophilia A, hence the belief that int22h-2 and int22h-3 are in opposite
      orientation to int22h-1. However, inversions involving int22h-2 are five times
      rarer than those involving its virtually identical copy: int22h-3. Recent
      sequencing has indicated that int22h-2 and int22h-3 form the internal part of the
      arms of an imperfect palindrome so that int22h-2, in the centromeric arm, has the
      same orientation as int22h-1 and, upon recombination with int22h-1, should
      produce deletions and duplications but not inversions. AIM: This work aims to
      provide rapid tests for all the mutations that can result from recombinations
      between the int22h sequences and to investigate whether int22h-2-related
      inversions causing hemophilia A arise in chromosomes, where the arms of the
      palindrome have recombined so that int22h-2 and int22h-3 swap places and
      orientation. PATIENTS/METHODS: Twenty patients with int22h-related inversions
      were examined together with a control and inversion carriers using reverse
      transcription-polymerase chain reaction (RT-PCR), long-range PCR and sequencing.
      RESULTS AND CONCLUSIONS: Analysis of mRNA in patients and a control provided
      evidence confirming the palindromic arrangement of int22h-2 and int22h-3 and the
      proposed inversion polymorphism that allows int22h-2 to be in the telomeric arm
      of the palindrome and in opposite orientation to int22h-1. New long-range PCR
      reactions were used to develop a single tube test that detects and discriminates
      inversions involving int22h-2 or int22h-3 and a two-tube test that can
      distinguish inversions, deletions, and duplications due to recombination between
      int22h sequences.

PMID- 16460443
TI  - Effect of MCM09, an active site-directed inhibitor of factor Xa, on B16-BL6
      melanoma lung colonies in mice.
AB  - BACKGROUND: Treatment with anticoagulant drugs has shown potential inhibitory
      effect on tumor invasion, although the relationship with clotting inhibition was
      not clear. AIM: The aim of our study was to evaluate the potential antitumor
      activity of MCM09, a newly developed, active site-directed, small molecule
      inhibitor of factor Xa (FXa) [WO0216312], and to relate the findings to
      anticlotting potency. METHODS: MCM09 (0.1-10 mg kg(-1)) or heparin (H; 10 mg kg(
      1)) was injected intravenously (i.v.), with 5 x 10(4) B16-BL6 melanoma cells, in
      C57BL/6 mice. Mice were killed after 18 days, to count lung colonies. Ex vivo
      anticoagulant activity was measured by activated partial thromboplastin time
      (APTT) on mouse plasma. RESULTS AND CONCLUSIONS: MCM09, a selective inhibitor of
      FXa (IC-50 = 2.4 nm against human FXa), inhibited in a dose-dependent manner B16
      BL6 melanoma lung colonies in mice. Mean lung metastasis number was 20.9 +/- 4.8
      in controls (n = 10), 1.2 +/- 0.4 in mice treated with H, 10 mg kg(-1) i.v. (P <
      0.01), 0.9 +/- 0.3, 9.2 +/- 2.2 and 15.5 +/- 2.6 in mice treated with MCM09, at
      10 (P < 0.01), 1 (P < 0.05) and 0.1 mg kg(-1) i.v. (ns), respectively. MCM09 (10
      mg kg(-1) i.v.) significantly prolonged APTT (57.1 +/- 10.2 s) 30 min after i.v.
      injection when compared with controls (25.3 +/- 1.6 s; P < 0.05). Lung colonies
      were 74.2-72.6% reduced by MCM09 (10 mg kg(-1)) given 60 or 120 min before cells,
      but not by MCM09 given 60 min thereafter, suggesting a direct cell interaction as
      a mechanism underlying antitumor activity.

PMID- 16460444
TI  - 11beta-Hydroxysteroid dehydrogenase type 1-driven cortisone reactivation
      regulates plasminogen activator inhibitor type 1 in adipose tissue of obese
      women.
AB  - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor
      of the fibrinolytic system and contributes to an increased risk of
      atherothrombosis in insulin-resistant obese patients. In adipose tissue, we have
      shown that PAI-1 is synthesized mainly in the visceral stromal compartment and is
      positively regulated by glucocorticoids. We have demonstrated that adipose tissue
      expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), an
      enzyme that catalyzes the conversion of inactive cortisone to active cortisol, is
      exaggerated in obese patients. OBJECTIVES: We hypothesized that increased action
      of 11beta-HSD-1 in adipose tissue of obese subjects may contribute to PAI-1
      overproduction. PATIENTS AND METHODS: Using in situ hybridization, we studied the
      expression of the mRNAs coding for PAI-1 and 11beta-HSD-1 in the stromal
      compartment of visceral adipose tissue obtained from obese women. The regulation
      of PAI-1 secretion from in vitro incubated tissue explants was also investigated.
      RESULTS: Regression analysis showed a significant positive linear relationship
      between PAI-1 and 11beta-HSD-1 mRNAs expression. In vitro incubation of adipose
      tissue explants demonstrated that cortisone stimulated PAI-1 gene expression and
      secretion, and that these effects were inhibited by co-incubation with the 11beta
      HSD inhibitor, glycyrrhetinic acid. CONCLUSIONS: Our data demonstrate that 11beta
      HSD-1-driven cortisone reactivation regulates adipose PAI-1 synthesis and
      secretion. They suggest that the increased PAI-1 synthesis and secretion observed
      in obese patients can be also related, at least in part, to an increased local
      conversion of cortisone to cortisol. Therefore, local cortisol metabolism in
      adipose tissue may be involved in increasing the risk of cardiovascular disease
      in obese subjects.

PMID- 16460445
TI  - Predictive value of sequential maternal anti-HPA-1a antibody concentrations for
      the severity of fetal alloimmune thrombocytopenia.
AB  - BACKGROUND: Fetal/neonatal alloimmune thrombocytopenia results from maternal
      immunization against fetal platelet alloantigens (HPAs), and the major risk is
      intracranial hemorrhage. The severity of thrombocytopenia increases in subsequent
      pregnancies, and antenatal therapy has been developed. Until now, the fetal
      status can only be assessed by fetal blood sampling, which carries a risk of
      fetal loss or premature delivery. OBJECTIVES: To develop non-invasive methods to
      gain information on the fetal condition. PATIENTS/METHODS: Quantification of the
      maternal anti-HPA-1a alloantibody concentration was performed with a standardized
      monoclonal antibody-specific immobilization of platelet antigens (MAIPA)
      procedure for 43 mothers. A correlation between this concentration and the
      fetal/neonatal platelet counts was studied. RESULTS: (i) Before antenatal
      therapy, there was a significant correlation between maternal anti-HPA-1a
      concentrations > or =250 AU mL(-1) and fetal thrombocytopenia (2-66 x 10(9) L(
      1)) whatever the gestational age (Fisher's exact test P = 0.0021). (ii) During
      subsequent pregnancies, we observed a decrease of the maternal anti-HPA-1a
      concentration for 14/19 women. Just before delivery, all women had anti-HPA-1a
      concentrations <250 AU mL(-1). In four cases, there was a therapy failure and the
      severely thrombocytopenic babies required postnatal therapy. CONCLUSION: The
      maternal anti-HPA-1a concentration could provide obstetricians with clinically
      useful information concerning the appropriateness and the timing of invasive
      monitoring procedures. However, though we observed a tendency toward a decrease
      in maternal antibody concentration after treatment, this finding does not allow
      us to draw any conclusions on the effectiveness of therapy.

PMID- 16460446
TI  - P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2
      generation in platelets occurs through regulation of Erk1/2 activation.
AB  - BACKGROUND: Thromboxane A2 (TXA2) is a positive feedback lipid mediator that is
      generated upon stimulation of platelets with various agonists. Aspirin works as
      an antithrombotic drug by blocking the generation of TXA2. The aim of this study
      was to evaluate the role of the purinergic P2Y receptors in thrombin-induced TXA2
      generation. RESULTS: PAR1-activating peptide (SFLLRN), PAR4-activating peptide
      (AYPGKF), and thrombin, induced the activation of cytosolic phospholipase A2
      (cPLA2), release of arachidonic acid (AA) from membrane-bound phospholipids, and
      subsequent TXA2 generation in human platelets. The actions of these agonists were
      significantly inhibited in the presence of the P2Y12 receptor antagonist, AR
      C69931MX, but not the P2Y1 receptor antagonist, MRS2179. In addition, AYPGKF- and
      thrombin-induced TXA2 generation was significantly reduced in platelets from mice
      dosed with clopidogrel, confirming the results obtained with the human platelets.
      Also, Pearl mouse platelets that lack releasable nucleotides generated
      significantly less TXA2 when compared with the wild-type littermates in response
      to PAR stimulation. Inhibition of extracellular signal-regulated protein kinase
      1/2 (Erk 1/2) activation using U0126, an inhibitor of MAP kinase kinase (MEK),
      suppressed PAR-mediated cPLA2 phosphorylation and TXA2 generation. Further,
      platelets that were pretreated with AR-C69931MX, as well as Pearl mouse
      platelets, displayed the reduced levels of Erk1/2 phosphorylation upon
      stimulation with the PAR agonists. CONCLUSIONS: Based on these findings, we
      conclude that thrombin-induced Erk1/2 activation is essential for PAR-mediated
      TXA2 generation, which is potentiated by the P2Y12 receptor-mediated signaling
      pathway but not the P2Y1 receptor-mediated signaling pathway. Finally, using
      selective inhibitors of Src kinases, we show that PAR-mediated Src activation
      precedes Erk1/2 activation.

PMID- 16460447
TI  - A role for PKCtheta in outside-in alpha(IIb)beta3 signaling.
AB  - Fibrinogen binding to platelets triggers alpha(IIb)beta3-dependent outside-in
      signals that promote actin rearrangements and cell spreading. Studies with
      chemical inhibitors or activators have implicated protein kinase C (PKC) in
      alpha(IIb)beta3 function. However, the role of individual PKC isoforms is poorly
      understood. Biochemical and genetic approaches were used to determine whether
      PKCtheta is involved in alpha(IIb)beta3 signaling. PKCtheta was constitutively
      associated with alpha(IIb)beta3 in human and murine platelets. Fibrinogen binding
      to alpha(IIb)beta3 stimulated the association of PKCtheta with tyrosine kinases
      Btk and Syk, and tyrosine phosphorylation of PKCtheta, Btk and the actin
      regulator, Wiskott-Aldrich syndrome protein (WASP). Mouse platelets deficient in
      PKCtheta or Btk failed to spread on fibrinogen. Furthermore, PKCtheta was
      required for phosphorylation of WASP-interacting protein on Ser-488, an event
      that has been linked to WASP activation of the Arp2/3 complex and actin
      polymerization in lymphocytes. Neither PKCtheta nor Btk were required for agonist
      induced inside-out signaling and fibrinogen binding to alpha(IIb)beta3. Thus,
      PKCtheta is a newly identified, essential member of a dynamic outside-in
      signaling complex that includes Btk and that couples alpha(IIb)beta3 to the actin
      cytoskeleton.

PMID- 16460448
TI  - Thrombin and PAR-1 stimulate differentiation of bone marrow-derived endothelial
      progenitor cells.
AB  - Endothelial progenitor cells (EPCs) from the bone marrow play an important role
      in vascular response to injury and ischemia. The mediators involved in the
      mobilization, recruitment, proliferation and differentiation of EPCs are not
      fully understood. In this study, the role of coagulation factor thrombin and
      protease-activated receptor-1 (PAR-1) on bone marrow-derived cell proliferation
      and differentiation was investigated. Bone marrow cells (BMCs) were isolated from
      C57/BL6 mice and plated on fibronectin-coated flasks. Cell characteristics,
      proliferation and the expression of endothelial cell markers were determined
      using immunohistochemistry, thymidine uptake and fluorescence activated-cell
      sorting (FACS), respectively. The results show that thrombin stimulated
      enrichment of bone marrow cells with endothelial morphology, exhibiting
      acetylated-low-density lipoprotein (LDL) uptake and isolectin staining. Thrombin
      or PAR-1-activating peptide produced a 2- to 3-fold increase in the total number
      of cells as well as an increase in vascular endothelial (VE)-cadherin-positive
      cells. Thrombin treatment of VE-cadherin-negative cells prepared after cell
      sorting resulted in the generation of 3- to 4-fold higher VE-cadherin-positive
      cells than the untreated cultures. Increase in VE-cadherin-positive cells was
      inhibited by hirudin and efegatran. These results provide first evidence for a
      novel activity of thrombin and PAR-1 on bone marrow progenitor cell proliferation
      and EPC differentiation, and suggest their potential role in vascular
      regeneration and recanalization of thrombus.

PMID- 16460450
TI  - Isolation and enumeration of circulating endothelial cells by immunomagnetic
      isolation: proposal of a definition and a consensus protocol.
AB  - BACKGROUND: Circulating endothelial cells (CECs) have been identified as markers
      of vascular damage in a variety of disorders, such as myocardial infarction,
      vasculitis, and transplantation. CD146-driven immunomagnetic isolation has gained
      widespread use, but the technique is hampered by the lack of a definition of CECs
      and the absence of a consensus for their enumeration. AIM: To evaluate several
      variables influencing immunomagnetic isolation of CECs, formulate a definition
      for CECs and propose a consensus protocol for their enumeration. METHODS: We
      devised a protocol based on CD146-driven immunomagnetic isolation and a
      subsequent confirmatory step with Ulex-Europaeus-Lectin-1 staining. In a multi
      center effort, we evaluated the preanalytical and analytical phases of this
      protocol. We evaluated the effects of storage, anticoagulation and density
      centrifugation, and compiled previous experience with this technique. RESULTS:
      Our protocol permitted unequivocal identification of CECs with acceptable
      reproducibility. There was an effect of storage time in that median cell numbers
      declined to only 87.5% of their baseline values during 24 h of storage at 4
      degrees C. Recovery was lower with citrate than with ethylene-diamine tetra
      acetic acid after 4 h of storage; density centrifugation was also associated with
      lower recovery. We provide a comprehensive list of technical recommendations and
      potential pitfalls. Finally, based on our experience with this protocol and a
      recent consensus workshop, we formulated a working definition for CECs.
      CONCLUSION: Our work represents an important step toward consensus regarding the
      CECs. Our recommendations represent the experience of three major centers and
      should now be scrutinized by others in the field.

PMID- 16460449
TI  - Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in
      atherosclerotic plaques.
AB  - BACKGROUND: Apoptosis of vascular cells is considered to be a major determinant
      of atherosclerotic plaque vulnerability and potential rupture. Plasmin can be
      generated in atherosclerotic plaques and recent in vitro data suggest that
      plasminogen activation may trigger vascular smooth muscle cell (VSMC) apoptosis.
      AIM: To determine whether plasminogen activation may induce aortic VSMC apoptosis
      ex vivo and in vivo. METHODS AND RESULTS: Mice with single or combined
      deficiencies of apolipoprotein E (ApoE) and plasminogen activator inhibitor-1
      (PAI-1) were used. Ex vivo incubation with plasminogen of isolated aortic tunica
      media from PAI-1-deficient mice induced plasminogen activation and VSMC
      apoptosis, which was inhibited by alpha2-antiplasmin. In vivo, levels of plasmin,
      active caspase 3 and VSMC apoptotic index were significantly higher in
      atherosclerotic aortas from mice with combined ApoE and PAI-1 deficiencies than
      in those from littermates with single ApoE deficiency. A parallel decrease in
      VSMC density was observed. CONCLUSIONS: These data strongly suggest that
      plasminogen activation may contribute to VSMC apoptosis in atherosclerotic
      plaques.

PMID- 16460451
TI  - Thrombocytopenia associated with the use of GPIIb/IIIa inhibitors: position paper
      of the ISTH working group on thrombocytopenia and GPIIb/IIIa inhibitors.

PMID- 16460452
TI  - Uncertain times for research on hemophilia and allied disorders.

PMID- 16460456
TI  - Personal reflections on fibrinolytic therapy of acute myocardial infarction.

PMID- 16460457
TI  - Fibrinolytic activity is highly influenced by long-term glycemic control in Type
      1 diabetic patients.

PMID- 16460458
TI  - Oral surgery in patients on oral anticoagulant therapy: a randomized comparison
      of different INR targets.

PMID- 16460459
TI  - Thromboembolic risk and bleeding in patients maintaining or stopping oral
      anticoagulant therapy during dental extraction.

PMID- 16460460
TI  - The effect of vitamin K supplementation on anticoagulant treatment.

PMID- 16460461
TI  - Influence of endotoxin challenge on protein S and C4b-binding protein in healthy
      subjects.

PMID- 16460462
TI  - Increased CD40 ligand expression on platelets is associated with cardiovascular
      events after total hip arthroplasty.

PMID- 16460464
TI  - Desmopressin, an unexpected link between nocturnal enuresis and inherited
      thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome).

PMID- 16460463
TI  - FRETS-VWF73: a rapid and predictive tool for thrombotic thrombocytopenic purpura.

PMID- 16460465
TI  - Changing epidemiology of the hemolytic uremic syndrome and thrombotic
      thrombocytopenic purpura in southern Iran.

PMID- 16460467
TI  - The protein S thrombin-sensitive region modulates phospholipid binding and the
      gamma-carboxyglutamic acid-rich (Gla) domain conformation in a non-specific
      manner.

PMID- 16460466
TI  - Clinical probability assessment of pulmonary embolism by the Wells' score: is the
      easiest the best?

PMID- 16460468
TI  - A genome search for genetic determinants of markers of protein C activation.

PMID- 16460469
TI  - More on: clinical experience with retrievable vena cava filters--results of a
      prospective observational multicenter study.

PMID- 16460470
TI  - More on: factor V Leiden and prothrombin G20210A polymorphisms as risk factors
      for miscarriage during a first-intended pregnancy: the matched case-control 'NOHA
      first' study.

PMID- 16460471
TI  - Mathematical and biological models of blood coagulation. A rebuttal.

PMID- 16460473
TI  - Non-alcoholic fatty liver disease: the unfolding monster?

PMID- 16460474
TI  - Does stress exacerbate liver diseases?
AB  - Although anecdotal comments on detrimental effects of psychosocial stress on
      liver diseases can be found even in the early literature, only recently has
      scientific evidence been reported. The present article reviewed such evidence to
      demonstrate how stress exacerbates liver diseases. A search of the literature
      from the last two decades was performed using MEDLINE by pairing 'psychological
      stress' with 'liver' or 'hepatitis.' Additional research was conducted by
      screening the bibliographies of articles retrieved in the MEDLINE search. The
      search results showed that the principal effectors of the activated hypothalamic
      pituitary-adrenal (HPA) axis, glucocorticoids, can exert a facilitative effect on
      the hepatic inflammatory response and even increase the risk of developing
      hepatocellular carcinoma. For certain liver diseases, defective HPA axis
      activation, which probably contributed to the exacerbation of the liver disease,
      has been reported. The efferent sympathetic/adrenomedullary system mainly
      contributes to the stress-induced exacerbation of liver diseases via its
      neurotransmitters, the catecholamines. In contrast, the efferent parasympathetic
      nervous system elicits an inhibitory effect on the development of hepatic
      inflammation. In conclusion, the pathophysiological interaction between stress
      and the liver appears to be regulated by the complex, dynamic networks of both
      the endocrine and autonomic nervous systems, which implies a further need for
      basic research into the involved mechanisms and for clinical evidence to apply
      psychosocial support to patients with chronic liver diseases.

PMID- 16460475
TI  - Does butyrate protect from colorectal cancer?
AB  - Butyrate, the four-carbon fatty acid, is formed in the human colon by bacterial
      fermentation of carbohydrates (including dietary fiber), and putatively
      suppresses colorectal cancer (CRC). Butyrate has diverse and apparently
      paradoxical effects on cellular proliferation, apoptosis and differentiation that
      may be either pro-neoplastic or anti-neoplastic, depending upon factors such as
      the level of exposure, availability of other metabolic substrate and the
      intracellular milieu. In humans, the relationship between luminal butyrate
      exposure and CRC has been examined only indirectly in case-control studies, by
      measuring fecal butyrate concentrations, although this may not accurately reflect
      effective butyrate exposure during carcinogenesis. Perhaps not surprisingly,
      results of these investigations have been mutually contradictory. The direct
      effect of butyrate on tumorigenesis has been assessed in a number of in vivo
      animal models, which have also yielded conflicting results. In part, this may be
      explained by methodological differences in the amount and route of butyrate
      administration, which are likely to significantly influence delivery of butyrate
      to the distal colon. Nonetheless, there appears to be some evidence that delivery
      of an adequate amount of butyrate to the appropriate site protects against early
      tumorigenic events. Future study of the relationship between butyrate and CRC in
      humans needs to focus on risk stratification and the development of feasible
      strategies for butyrate delivery.

PMID- 16460476
TI  - Virtual gastroscopy: initial attempt in North American patients.
AB  - BACKGROUND: Virtual endoscopy (VE) is a new evolving technology that describes
      the 3-D reconstruction of medical image scans to create a visualization similar
      to that produced by fiber-optic and video endoscopy. The present study was
      carried out to establish the feasibility of this technique in the upper
      gastrointestinal tract. METHODS: Ten patients who underwent upper endoscopy for
      different clinical reasons and who were found to have a normal or near normal
      examination underwent a spiral computed tomography scan of the lower chest and
      abdomen. A 3-D image was reconstructed using the Freeflight software. RESULTS:
      The anatomy of the stomach including the lumen, the cardia, the pylorus, gastric
      folds and the incisura angularis were well-visualized. It was not possible to
      visualize the esophagus by VE because the lumen was unable to be kept patent long
      enough to provide accurate imaging. CONCLUSIONS: The present preliminary study
      has demonstrated the feasibility of performing virtual gastroscopy. Further
      development in this area is needed before any routine clinical application.

PMID- 16460478
TI  - Endoscopic ultrasonograph evaluation of vascular structures in the gastric cardia
      predicts esophageal variceal recurrence following endoscopic treatment.
AB  - BACKGROUND AND AIM: In patients with portal hypertension, early recurrence of
      esophageal varices often occurs following endoscopic variceal ligation therapy or
      ligation and injection-sclerotherapy combined treatment. To assess the recurrence
      risk following endoscopic treatment, this study investigated the association
      between recurrence-free time and severity of esophagogastric vascular structures
      before treatment as determined by endoscopic ultrasonography. METHODS: Sixty
      three patients with esophageal varices at high bleeding risk were treated by
      endoscopic variceal ligation therapy or ligation and injection-sclerotherapy
      combined treatment. Before the treatment, conventional endoscopy and endoscopic
      ultrasonography with a 20-MHz catheter probe were performed. Submucosal,
      perforating and adventitial veins in the esophagus and gastric cardia were
      examined. According to the endoscopic ultrasonography findings, the vascular
      structures were classified into two grades: mild and severe. The relationships
      between the endoscopic ultrasonography grades and variceal recurrence-free time
      were analyzed by the Kaplan-Meyer method. RESULTS: Patients with severe as
      opposed to mild grade perforating veins in the gastric cardia had a significantly
      shorter recurrence-free time (P < 0.05). Those with severe paracardial veins also
      had a significantly shorter recurrence-free time (P < 0.01). CONCLUSION:
      Endoscopic ultrasonography analysis for gastric cardial vascular structures
      before endoscopic treatment can be useful to predict the recurrence of esophageal
      varices.

PMID- 16460477
TI  - Effect of sildenafil on gastric emptying in healthy adults.
AB  - BACKGROUND AND AIM: Phosphodiesterase type 5 hydrolyzes and inactivates cyclic
      guanosine monophosphate produced by the nitric oxide-stimulated guanylate
      cyclase. Sildenafil is a potent, reversible, and highly selective inhibitor of
      this phosphodiesterase. It causes smooth muscle relaxation by increasing
      intracellular concentrations of cyclic guanosine monophosphate. The aim of this
      study was to test the hypothesis that sildenafil alters gastric emptying and the
      intragastric distribution of food in healthy adults. METHODS: Nine normal
      subjects (mean age 28 years, range 25-33) were given a placebo or a tablet of
      sildenafil (50 mg) at different times along with radio-opaque markers. A gastric
      emptying scan was used to calculate the t(1/2) for gastric emptying (the time
      taken for the initial radioactivity to fall by 50%). Intragastric food
      distribution was also assessed using the gastric emptying scan to calculate
      proximal gastric emptying t(1/2), the proximal volume (the highest activity value
      in the proximal stomach at any time point in the study), and the distal volume
      (the highest activity value in the distal stomach at any time point in the study.
      Gastric emptying of an indigestible solid meal was assessed by calculating
      gastric clearance of radio-opaque markers. RESULTS: Sildenafil did not change
      total gastric emptying or gastric clearance of radio-opaque markers. It shortened
      the proximal T(1/2), decreased proximal volume, and significantly increased
      distal volume. CONCLUSION: Sildenafil alters the intragastric distribution of
      food rather than causing gastric stasis.

PMID- 16460480
TI  - Factors predicting success of endoscopic variceal ligation for secondary
      prophylaxis of esophageal variceal bleeding.
AB  - INTRODUCTION: Endoscopic obliteration of esophageal varices by endoscopic
      variceal ligation (EVL) is an effective form of secondary prophylaxis. However,
      there is no consensus regarding the technical aspects of EVL for secondary
      prophylaxis. The present study compares the technical aspects of EVL (frequency
      of sessions, number of sessions and number of bands used) in patients who rebled
      following secondary prophylaxis of esophageal varices by EVL compared to those
      who did not rebleed. METHODS: All patients who underwent EVL for treatment of
      acute variceal bleeding followed by EVL for secondary prophylaxis and who
      subsequently developed recurrent variceal bleeding at Mayo Clinic, Rochester
      between January 1995 and May 2003 were identified. A control group of patients
      undergoing EVL for secondary prophylaxis who did not rebleed was identified.
      RESULTS: During the study period, 216 patients with acute esophageal variceal
      hemorrhage underwent emergent EVL treatment with follow-up EVL for secondary
      prophylaxis, of whom 20 (9.3%) subsequently rebled. Both rebleeding and non
      rebleeding patient groups were well-matched with respect to liver function (Child
      Pugh class), number and size of variceal trunks, endoscopic stigmata of
      hemorrhage and beta-blocker usage. The median interval between EVL sessions in
      the rebleeding group (2 weeks, interquartile range 0-2 weeks) was significantly
      shorter compared to the non-rebleeding group (5 weeks, interquartile range 3-7
      weeks; P = 0.004). Adjusting for age, gender, and Child-Pugh class, interbanding
      interval >/= 3 weeks was associated with increased likelihood of not rebleeding,
      hazard ratio 3.84 (95% confidence interval: 1.69-11.79; P = 0.0007). CONCLUSIONS:
      These findings demonstrate the importance of technical aspects of EVL on patient
      outcome, suggesting the benefit of longer interbanding intervals. Future
      prospective studies are required to define the optimal intersession interval.
      Standardizing procedural aspects of EVL will aid in objectively evaluating the
      benefit of this procedure when compared to other modalities such as medical
      treatment.

PMID- 16460479
TI  - Tetracycline, metronidazole and amoxicillin-metronidazole combinations in proton
      pump inhibitor-based triple therapies are equally effective as alternative
      therapies against Helicobacter pylori infection.
AB  - BACKGROUND: A proton pump inhibitor (PPI)-based triple therapy with
      clarithromycin (CAM) and amoxicillin (AMPC) is now a standard regimen for
      Helicobacter pylori (HP) eradication in Japan. However, the CAM-resistant rate
      has increased recently and alternative therapies are sorely needed. Therefore the
      aim of the present study was to evaluate the effectiveness and safety of the PPI
      tetracycline (TC)-metronidazole (MNZ) regimen (the PTM regimen) as an alternative
      therapy in comparison with the PPI-AMPC-MNZ (PAM) regimen. METHODS: Sixty-four HP
      positive patients visiting the HP-eradication clinic in Tokai University Hospital
      from July 1998 to March 2003 were treated with either PTM or PAM as alternative
      therapies. The HP eradication was assessed by urea breath test (UBT), HP stool
      antigen test, or HP culture method more than 2 months after completion of the
      treatments. The drug resistances against CAM, AMPC, TC, and MNZ were assessed by
      the agar dilution method. RESULTS: Fifty-six patients (26 PTM and 30 PAM)
      completed medication and evaluation of the eradication. The eradication rates of
      PTM were 82.8% (24/29) and 92.3% (24/26), while those of PAM were 74.3% (26/35)
      and 89.7% (26/29) by intention-to-treat and per-protocol analysis, respectively.
      The differences between the regimens were not statistically significant. There
      were no severe adverse effects observed in either of the regimens. The drug
      resistance analyses showed 15 CAM- and one MNZ-resistant cases but no TC or AMPC
      resistance in the available 25 samples. CONCLUSION: The PTM and PAM regimens were
      equally effective and safe as alternative HP eradication therapies. And PTM would
      be particularly useful in penicillin allergy cases.

PMID- 16460481
TI  - Expression of endothelin receptors in the gastric mucosa of portal hypertensive
      rats.
AB  - BACKGROUND: Portal hypertensive gastropathy is an abnormal circulatory state in
      gastric mucosa with vascular dilatation due to portal hypertension. The aim of
      the present study was to evaluate expression of endothelin receptors and their
      roles in the portal hypertensive gastric mucosa. METHODS: Portal hypertensive
      rats were generated by staged portal vein occlusion. Expression of endothelin-A
      receptor and endothelin-B receptor mRNA was examined by reverse transcriptase
      polymerase chain reaction, and protein were examined by immunohistochemistry. The
      changes of mucosal microcirculation by endothelin receptor antagonists were
      measured with in vivo microscope. RESULTS: Expression of endothelin-A receptor
      mRNA was increased significantly in portal hypertensive rats in comparison with
      sham-operated control rats (P < 0.05). There was no significant difference
      between the two groups in endothelin-B receptor mRNA expression. Vessels of the
      gastric mucosa were dilated, and intravessel blood flow was increased
      significantly in the portal hypertensive group (P < 0.05). Diameters of mucosal
      vessels and blood flow were increased significantly by endothelin-A receptor
      antagonist (BQ-485) in the portal hypertensive rats. Endothelin-B receptor
      antagonist (IRL-1038) had no significant effect on mucosal microcirculation.
      CONCLUSION: These data suggest that increased expression of endothelin-A receptor
      in the portal hypertensive gastric mucosa may be related to the regulation of
      gastric microcirculation.

PMID- 16460482
TI  - Effect of the non-steroidal anti-inflammatory drug sulindac on colorectal
      adenomas of uncolectomized familial adenomatous polyposis.
AB  - BACKGROUND: The aim of the present study was to elucidate the effect of sulindac
      on uncolectomized familial adenomatous polyposis (FAP). METHODS: Seven FAP
      patients (SU group) without proctocolectomy were given sulindac 300 mg/day orally
      for 12 months. Six FAP patients without sulindac (non-SU group) served as
      controls. Colorectal lesions were assessed by protrusion index (no. radiolucent
      areas/cm(2); PI) under barium enema examination and non-polypoid lesion were
      assessed under chromoscopy prior to and at the end of the observation period. In
      the SU group, germline adenomatous polyposis coli (APC) mutation was determined
      by protein truncation test. RESULTS: In the SU group, PI decreased significantly
      in the distal colon (from 3.0 +/- 1.1 to 1.1 +/- 0.8/cm(2), P < 0.02) and in the
      proximal colon (from 3.4 +/- 2.4 to 0.9 +/- 1.3/cm(2), P < 0.02). The PI in the
      non-SU group slightly but significantly increased in the distal colon (from 1.0
      +/- 0.8 to 1.2 +/- 0.9/cm(2); P < 0.05) and it remained unchanged in the proximal
      colon (from 0.6 +/- 0.3 to 0.7 +/- 0.3/cm(2); P > 0.05). Chromoscopy at the end
      of observation identified non-polypoid lesions in five patients in the SU group,
      whereas such lesions were not found in the non-SU group (71% vs 0%, P = 0.016).
      Decrease in PI was not different among distal APC mutation (exons 1-9), proximal
      APC mutation (exons 10-15) and negative mutation. CONCLUSION: Sulindac reduces
      colorectal adenomas of protruding type in uncolectomized FAP. The effect of
      sulindac may be unrelated to genotype of FAP.

PMID- 16460483
TI  - Evaluation of endoscopic and histological findings in Helicobacter pylori
      positive Japanese young adults.
AB  - BACKGROUND AND AIM: Many studies have shown that Helicobacter pylori infection is
      associated with chronic gastritis, peptic ulcers and gastric carcinoma in adults.
      However, little is known about these associations in the younger population. The
      aim of this study was to clarify endoscopic and histological findings in H.
      pylori-positive young adults. METHODS: Two hundred consecutive outpatients
      younger than 29 years old undergoing esophago-gastroduodenal endoscopy at four
      hospitals between 2001 and 2002 were eligible for this study. At endoscopy, three
      biopsy specimens were obtained from the mid-antrum, the angulus and the mid
      corpus. Endoscopic and histological interpretations were based on the updated
      Sydney System. H. pylori infection was determined by histology and serology.
      RESULTS: The rates of H. pylori infection were 1.2% (1/86) in normal, 95.8%
      (46/48) in gastritis, 97.8% (45/46) in duodenal ulcers, 100% (17/17) in gastric
      ulcers, and 100% (3/3) in gastric carcinomas. Endoscopic findings in 112 H.
      pylori-positive patients were 25 normal (22.3%), 38 atrophy (33.9%), 18 erosion
      (16.1%), and 31 nodularity (27.7%). Histological findings of H. pylori-positive
      patients in the anturm revealed mononuclear cell and neutrophil infiltration in
      100%, and atrophy in 27.7%. Histological findings of H. pylori-positive patients
      in the corpus revealed mononuclear cell infiltration in 75%, neutrophil
      infiltration in 60.7%, and atrophy in 28.6%. CONCLUSIONS: The study shows that H.
      pylori infection is strongly associated with chronic gastritis and peptic ulcers,
      and that histological corpus gastritis was found with high frequency in Japanese
      young adults.

PMID- 16460484
TI  - Effectiveness of minocycline-based triple therapy for eradication of Helicobacter
      pylori infection.
AB  - BACKGROUND: Widespread use of eradication therapy for Helicobacter pylori has
      increased the prevalence of clarithromycin-resistant strains. The purpose of the
      present paper was to measure the in vitro antibacterial activity of minocycline
      against H. pylori, and study the effectiveness of minocycline-based first- and
      second-line eradication therapies. METHODS: For first-line therapy, 79 patients
      were randomly assigned to the treatment with rabeprazole, amoxicillin, and
      clarithromycin or with rabeprazole, amoxicillin, and minocycline. For second-line
      therapy, 88 patients were tested for sensitivity to metronidazole: 67 patients
      with metronidazole-sensitive strains received a 7-day course of rabeprazole,
      minocycline, and metronidazole; the remaining 21 patients were given a 7-day
      course of rabeprazole, minocycline, and faropenem. RESULTS: There was virtually
      no resistance to minocycline among the strains tested. The eradication rate of H.
      pylori infection in first-line therapy was significantly lower for minocycline
      containing regimen (38.5%, 15/39) than for clarithromycin-containing regimen
      (82.5%, 33/40; P < 0.01). For second-line therapy, a high eradication rate
      against metronidazole-sensitive strains was obtained with rabeprazole,
      minocycline and metronidazole (85%, 57/67). CONCLUSIONS: A combination of
      rabeprazole, minocycline, and metronidazole is safe and effective for second-line
      therapy of H. pylori infection. Because this regimen can be administered to
      patients with penicillin allergy and patients who suffer adverse reactions to
      amoxicillin, such as diarrhea and other digestive symptoms, it should be
      considered useful for second- and third-line eradication therapy.

PMID- 16460485
TI  - Development and validation of a functional dyspepsia-related quality of life (FD
      QOL) scale in South Korea.
AB  - BACKGROUND: Quality of life (QOL) in patients with functional dyspepsia in South
      Korea has never been studied, mostly due to the lack of a psychometrically
      validated disease-specific instrument for measuring the QOL. The aim of the
      present study was to develop and validate a QOL scale for patients with
      functional dyspepsia. METHODS: A Functional Dyspepsia-Related QOL (FD-QOL) scale
      was developed and validated as follows: item generation, pilot test, and
      psychometric test. Patients with functional dyspepsia (n = 220) were recruited
      from seven university hospitals. The participants were asked to complete the
      preliminary item-generated FD-QOL, the Short Form-36 (SF-36), and the Index of
      Dyspepsia Symptoms-Korean (IDS-K). The data were analyzed using factor analysis,
      correlation, anova, and Cronbach's alpha. RESULTS: Twenty-three items were
      generated based upon content validity. Factor analysis extracted a four-factor
      solution, and two items were deleted because they were not loaded significantly
      on any factor. The FD-QOL was correlated with the SF-36 subscales, of which
      scores were differentiated according to the levels of dyspepsia symptoms.
      Cronbach's alpha of the FD-QOL was 0.94. CONCLUSIONS: The FD-QOL scale is a rapid
      and easily applicable instrument with excellent psychometric properties of
      content, factorial, convergent, and known-groups validity, and internal
      consistency reliability in Korean patients with functional dyspepsia.

PMID- 16460486
TI  - Effects of Silybum marianum on serum hepatitis C virus RNA, alanine
      aminotransferase levels and well-being in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Silybum marianum is a herbal preparation commonly used by
      subjects with chronic hepatitis C (CHC). The aims of this pilot study were to
      assess the efficacy and safety of S. marianum on serum hepatitis C virus (HCV)
      RNA, alanine aminotransferase levels and well-being in patients with CHC.
      METHODS: Twenty-four subjects with CHC were enrolled into a randomized, double
      blind, placebo-controlled, crossover study. Subjects received 12 weeks of S.
      marianum (either 600 mg or 1200 mg/day) and placebo separated by a 4-week washout
      interval. Baseline biochemical, virological, psychological and quality-of-life
      tests were performed, with biochemical tests repeated monthly, and HCV RNA titer
      and quality-of-life and psychological assessments repeated at the end of both
      treatment periods. RESULTS: Seventeen patients completed the trial. Mean changes
      in HCV RNA titers, serum ALT levels and Short Form-36 scores were not
      significantly different for subjects on S. marianum compared to those on placebo.
      There was no significant change in mean State-Trait Anxiety Inventory State
      Anxiety scores on S. marianum from baseline. Adverse events were similar with S.
      marianum and placebo. CONCLUSIONS: S. marianum is well tolerated in subjects with
      CHC, but does significantly affect serum HCV RNA, alanine aminotransferase
      levels, quality of life or psychological well-being in subjects with this
      condition.

PMID- 16460487
TI  - Long-term monitoring of platelet count, as a non-invasive marker of hepatic
      fibrosis progression and/or regression in patients with chronic hepatitis C after
      interferon therapy.
AB  - BACKGROUND: Platelet count has been shown to correlate with the hepatic fibrosis
      stage in chronic hepatitis C (CHC). The aim of the present study was to assess
      hepatic fibrosis progression or regression of CHC patients by long-term
      monitoring of the platelet count. METHODS: A total of 429 interferon (IFN)
      treated CHC patients were studied. Follow-up data on the platelet count were
      collected every 6 months after IFN therapy. The IFN response was defined as
      follows: complete responders (CR, n = 121) demonstrating persistent clearance of
      serum hepatitis C virus (HCV) RNA; biochemical responders (BR, n = 94)
      demonstrating alanine aminotransferase (ALT) normalization for >/=6 months
      without eradication of HCV-RNA; and non-responder (NR, n = 214) demonstrating all
      other patterns. RESULTS: In comparison with the baseline level, mean platelet
      count increased in the CR group from 0.5 years after IFN therapy (for each point,
      P < 0.01), but significantly decreased in the NR group from 1 year after IFN
      therapy (for each point, P < 0.01). In the BR group, an increase in mean platelet
      count was observed from 0.5 to 3.5 years following IFN therapy (for each point, P
      < 0.01), followed by a gradual decrease. CONCLUSION: An increase from baseline
      values in platelet count was observed, regardless of the presence of HCV-RNA, in
      both the CR and BR groups, suggesting the importance of ALT normalization in
      preventing hepatic fibrosis progression in IFN-treated CHC patients.

PMID- 16460488
TI  - Multiple non-tumorous arterioportal shunts due to chronic liver disease mimicking
      hepatocellular carcinoma: outcomes and the associated elevation of alpha
      fetoprotein.
AB  - PURPOSE: To elucidate the morphologic appearance of small non-tumorous
      arterioportal (AP) shunts mimicking hepatocellular carcinoma on helical computed
      tomography (CT), their associated outcomes, and their relationship with alpha
      fetoprotein levels in patients with chronic liver disease. MATERIALS AND METHODS:
      Ten patients with multiple AP shunts on dynamic helical CT were evaluated. A non
      tumorous AP shunt was defined as no increase or spontaneous regression in size on
      follow-up CT scans. The number and shape of shunts more than 5 mm in diameter
      were studied on a segment-by-segment basis on the initial CT scan, and compared
      with those on follow-up CT scans. Alpha-fetoprotein levels were measured at the
      same time as CT scanning was performed. RESULTS: Ten patients with 86 AP shunts
      (range 0.5-3.8 cm; mean 1.2 cm) underwent arterial, portal and delayed phase
      imaging of the entire liver. The AP shunts were geographic (44%), round (33%) or
      wedge-like (23%) in shape. All shunts changed from high- to iso-attenuation on
      the delayed phase CT. A follow-up CT (mean 73 days) revealed spontaneous
      disappearance in all but three (97%) of the 86 AP shunts. Furthermore, 16 new
      shunts appeared in different segments from the primary ones in four patients. The
      rapid elevation of alpha-fetoprotein levels to 5-10-fold higher than the baseline
      level was recognized at the same time as the initial appearance of AP shunts in
      three patients (30%). Further follow-up CT scans detected solitary hepatocellular
      carcinomas in four patients at a mean 1283 days after the initial CT. The
      location of the hepatocellular carcinomas was quite different from those of the
      initially recognized AP shunts. CONCLUSIONS: Non-tumorous AP shunts varied in CT
      appearance and demonstrated iso-attenuation in the delayed phase, most of which
      disappeared within 4 months. For these multiple small stains in chronic liver
      disease, periodic follow-up CT is recommended rather than alternative invasive
      interventions, even though there was an association with rapid elevation of alpha
      fetoprotein levels.

PMID- 16460489
TI  - Rheumatoid-like nodules in the spleen: new extraintestinal manifestation of
      Crohn's disease?
AB  - A 26-year-old, HLA-B27 positive man with steroid dependent Crohn's disease
      presented with abdominal lymphadenopathy and multiple abscess-like masses in the
      spleen and liver 2 years after the initial diagnosis. A biopsy of one of the
      liver lesions showed epitheloid cell granuloma, no microorganisms were detected
      despite intensive investigations. The liver lesions and the lymphadenopathy
      repeatedly disappeared completely in response to prednisolone pulse therapy while
      the lesions in the spleen remained practically unchanged. One year later, on
      immunosuppressive therapy with azathioprine and low-dose prednisolone, the
      patient's condition exacerbated with development of fever, disseminated
      arthritides and enlargement of the splenic lesions. Following ineffective
      antimicrobial treatment, a splenectomy was carried out. Histology showed that the
      splenic parenchyma was filled with abacterial, rheumatoid granulomas. After a
      renewed flare-up of severe extraintestinal symptoms, the patient is now
      asymptomatic on immunosuppressive therapy with azathioprine and prednisolone.
      Abdominal lymphadenopathy is no longer present and the liver lesions are
      regressing. The intermittent course and the positive response to
      immunosuppressive therapy point to a further extraintestinal manifestation of
      Crohn's disease.

PMID- 16460490
TI  - Liver biopsy in the diagnosis of visceral leishmaniasis.
AB  - AIM: To determine whether liver biopsy might be useful in the diagnosis of
      visceral leishmaniasis when bone marrow examination and serologic tests are
      inconclusive. METHODS: Over a 10-year period, liver biopsy was performed in five
      children with suspected visceral leishmaniasis when indirect hemagglutination
      tests and bone marrow aspirations were not diagnostic. RESULTS: Leishmania
      amastigotes were seen in Kupffer cells in all patients. The accompanying liver
      histopathological findings were ischemic necrosis in two children, macrovesicular
      steatosis in two children, portal inflammatory inflammation in two children, and
      piecemeal necrosis in one child. During the study period, 32 additional pediatric
      visceral leishmaniasis cases were diagnosed by bone marrow examination.
      CONCLUSION: Liver biopsy can be recommended for diagnosing suspected visceral
      leishmaniasis in children when serology and bone marrow aspiration are
      inconclusive.

PMID- 16460491
TI  - Terlipressin versus albumin in paracentesis-induced circulatory dysfunction in
      cirrhosis: a randomized study.
AB  - BACKGROUND: Therapeutic paracentesis in patients with cirrhosis induces arterial
      vasodilatation, causes a decrease in effective arterial blood volume and leads to
      circulatory dysfunction, which can be prevented by intravenous albumin. However,
      the use of albumin, being a blood product, is controversial. Recently,
      terlipressin, a vasoconstrictor, has been successfully used to combat this
      adverse effect of therapeutic paracentesis. Therefore, the aim of the present
      study was to investigate the preventive effect of terlipressin on paracentesis
      induced circulatory dysfunction in patients with cirrhosis after therapeutic
      paracentesis and compared with that of intravenous albumin. METHODS: Forty
      patients with cirrhosis and tense ascites underwent therapeutic paracentesis with
      albumin or terlipressin in a randomized pilot study at a tertiary center.
      Effective arterial blood volume was assessed by measuring plasma renin activity
      at baseline and at 4-6 days after treatment. RESULTS: Effective arterial blood
      volumes as indicated by plasma renin activity before and 4-6 days after
      paracentesis did not differ in the two groups (19.15 +/- 12.1 to 20.33 +/- 12.8
      ng/mL per h, P = 0.46 in the albumin group; and 20.11 +/- 10.6 to 21.08 +/- 10.52
      ng/mL per h, P = 0.44 in the terlipressin group). Plasma aldosterone
      concentrations before and 4-6 days after paracentesis were also similar in both
      groups (1334.75 +/- 1058 to 1440.0 +/- 1161 pg/mL, P = 0.06 in the albumin group;
      and 1473.0 +/- 1168 to 1572.29 +/- 1182 pg/mL, P = 0.24 in the terlipressin
      group). Both terlipressin and albumin prevented paracentesis-induced renal
      impairment in these patients. CONCLUSIONS: Terlipressin may be as effective as
      intravenous albumin in preventing paracentesis-induced circulatory dysfunction in
      patients with cirrhosis after therapeutic paracentesis.

PMID- 16460492
TI  - Effect of combination therapy with ribavirin and high-dose interferon-alpha2b for
      24 weeks in chronic hepatitis C.
AB  - BACKGROUND AND AIM: The aim of the present study was to determine whether a 24
      week course of combination therapy with ribavirin and high-dose interferon
      alpha2b (IFN-alpha2b) could provide an acceptable treatment efficacy in chronic
      hepatitis C (CHC). METHODS: Seventy-six patients with CHC whose serum hepatitis C
      virus (HCV) RNA levels were more than 100 kIU/mL on quantitative polymerase chain
      reaction (PCR) assay were included. The patients were assigned to two different
      dose groups of IFN-alpha2b: group A (n = 39) received 6 MU and group B (n = 37)
      received 10 MU. Each group received the dose daily for 14 days then three times
      per week for a total of 24 weeks. In addition, HCV genotype 1b patients in group
      A and group B were classified into group C (n = 20) and D (n = 29), respectively.
      All patients received 600 or 800 mg ribavirin per day. RESULTS: Sustained
      response rates in group A were significantly higher than those in group B
      (66.7%vs 35.1%, intent-to-treat, P = 0.0060). However, sustained response rates
      in group C were not different from those in group D (45.0%vs 20.7%, intent-to
      treat, P = 0.0696). The proportion of patients who discontinued the treatment or
      reduced drug dosage because of adverse events was significantly higher in group B
      than in group A (27.0%vs 7.69%, P = 0.0224). CONCLUSION: A 24-week course of
      combination therapy with ribavirin and 6 MU IFN-alpha2b had an acceptable
      efficacy with fewer adverse events than that with ribavirin and 10 MU IFN-alpha2b
      in CHC.

PMID- 16460493
TI  - Kupffer cell function during the erythocytic stage of malaria.
AB  - BACKGROUND AND AIM: Previous studies using isolated perfused rat liver in vivo
      have suggested that during the erythrocytic phase of malaria infection, overall
      phagocytosis by Kupffer cells is enhanced. The aim of the present study was to
      further investigate the individual phagocytic capacity and prostaglandin E(2)
      (PGE(2)) secretion of isolated Kupffer cells in vitro, and the
      immunohistochemical characteristics of Kupffer cells in vivo. METHODS: Malaria
      was induced in male Sprague-Dawley rats (n = 12) by inoculation with parasitized
      red cells containing Plasmodium berghei. Kupffer cells were isolated by
      centrifugal elutriation. RESULTS: A significantly increased yield of Kupffer
      cells was obtained from malaria-infected livers compared to controls (36.7 +/-
      4.5 vs 11.8 +/- 1.1 x10(6) cells, P < 0.0001, n = 12). There was an increased
      internalization by phagocytosis of [(3)H]-BSA latex microspheres after 60 min in
      malaria-infected Kupffer cells compared to controls (65.05 +/- 1.5 vs 48.6 +/-
      0.7, P < 0.001, n = 12). PGE(2) secretion into the cell culture medium was
      significantly suppressed in malaria-infected Kupffer cells compared to controls
      (1167 +/- 88 vs 4537 +/- 383 pg per 10(6) cells, P < 0.001, n = 5). Staining of
      ED1, ED2 and PCNA was greater in malaria-infected livers compared to control.
      CONCLUSION: The results indicate that the number of Kupffer cells is
      significantly increased and their phagocytic activity on a cell-by-cell basis is
      enhanced during the erythrocytic stage of malaria.

PMID- 16460495
TI  - Education and imaging. Gastrointestinal: Gastrointestinal metastases from
      malignant melanoma.

PMID- 16460494
TI  - Thyroid dysfunction in patients with chronic hepatitis C receiving a combined
      therapy of interferon and ribavirin: incidence, associated factors and prognosis.
AB  - BACKGROUND AND AIMS: Interferon (IFN) plus ribavirin therapy for chronic
      hepatitis C (CHC) virus infection has been associated with thyroid dysfunction.
      The goal of our current study was to elucidate predictive factors of: (i) thyroid
      dysfunction associated with combination therapy; and (ii) long-term reversibility
      of thyroid dysfunction. METHODS: In total, 461 patients with CHC and normal
      baseline thyroid functions were enrolled. All patients received IFN-alpha-2b, 3
      or 5 million units thrice weekly, or pegylated (PEG)-IFN-alpha-2b 80 or 100
      microg weekly combined with ribavirin 1-1.2 g daily for 24-48 weeks. Assays for
      serum thyroid stimulating hormone (TSH) and free thyroxine were performed.
      RESULTS: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L)
      had developed in 58 patients (12.6%). Female gender was significantly associated
      with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence
      interval (CI) = 1.6-5.1). The incidence of thyroid dysfunction was similar for
      standard IFN and PEG-IFN-treated patients (49/391 vs 9/70; P = 1.00). Under a
      nested case-control design, detailed laboratory assessment was carried out on
      frozen serum samples from patients and age- (+/- 5 years) and sex-matched
      controls (n = 58). Multivariate analysis revealed significant association between
      higher positive rates of pretreatment TMA and patients who developed thyroid
      dysfunction (OR = 5.8, 95% CI = 1.2-27.9). Ten patients ( approximately 2%)
      remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For
      these patients, no risk factor can predict the reversibility of thyroid function.
      CONCLUSIONS: Female gender and pretreatment TMA positivity are associated with
      thyroid dysfunction. Long-term thyroid dysfunction may persist in a small group
      of patients ( approximately 2%).

PMID- 16460496
TI  - Education and imaging. Gastrointestinal: Giant liposarcoma.

PMID- 16460497
TI  - Education and imaging. Hepatobiliary and pancreatic: hepatic abscess associated
      with a hepatoenteric fistula.

PMID- 16460498
TI  - Education and imaging. Gastrointestinal: huge angiomyolipoma.

PMID- 16460499
TI  - Education and imaging. Gastrointestinal: solitary fibrous tumor.

PMID- 16460500
TI  - Association of celiac disease with non-cirrhotic portal fibrosis.
AB  - Both celiac disease and non-cirrhotic portal fibrosis are known to be associated
      with various autoimmune diseases and have numerous immunological abnormalities.
      Herein two patients with celiac disease having associated non-cirrhotic portal
      fibrosis are reported. An autoimmune link between the two conditions is likely to
      explain coexistence in the same patient.

PMID- 16460501
TI  - Giant accessory liver lobe.

PMID- 16460502
TI  - Rectal malignant lymphoma complicating ulcerative colitis treated with long-term
      cyclosporine A.

PMID- 16460503
TI  - Acute liver failure as presenting feature of tyrosinemia type 1 in a child with
      primary HHV-6 infection.

PMID- 16460504
TI  - Intra-abdominal lymphangioma: usefulness of endoscopic ultrasound and laparoscopy
      in diagnosis.

PMID- 16460505
TI  - cGMP modulates gene transcription and cation transport in Arabidopsis roots.
AB  - Summary The occurrence of the second messenger 3',5'-cyclic guanyl monophosphate
      (cGMP) has been shown in a number of plant species, including barley, tobacco and
      Arabidopsis. Physiological processes where cGMP signalling has been observed, or
      has been inferred, to play a role include chloroplast development, alpha-amylase
      production in aleurone tissue, NO-dependent expression of defence-related genes
      and salt/osmotic stress. In most cases, it is unknown how cGMP exerts its effects
      and what the downstream targets are. A transcriptomics approach was therefore
      used to identify putative targets for cGMP signalling. Root exposure to 10 mum
      membrane permeable cGMP induced changes in abundance for many transcripts
      involved in metabolism, gene transcription, signalling and defence. In
      particular, monovalent cation transporters such as non-selective ion channels and
      cation:proton antiporters were found to be affected in cGMP exposed roots. In
      addition, exposure to cGMP was found to modulate influx and efflux of the
      monovalent cations Na+ and K+.

PMID- 16460507
TI  - Divergence of duplicated genes in maize: evolution of contrasting targeting
      information for enzymes in the porphyrin pathway.
AB  - The divergence of sequence and expression pattern of duplicated genes provides a
      means for genetic innovation to occur without sacrificing an essential function.
      The cpx1 and cpx2 genes of maize are a singular example of duplicated genes that
      have diverged by deletion and creation of protein targeting information. The cpx
      genes encode coproporphyrinogen III oxidase ('coprogen oxidase'), which catalyzes
      a step in the synthesis of chlorophyll and heme. In plants, this enzyme has been
      found exclusively in the plastids. The cpx1 and cpx2 genes encode almost
      identical, catalytically active enzymes with distinctive N-terminal peptide
      sequences. The cpx1 gene encodes the expected plastid transit peptide, but this
      region is deleted from the cpx2 gene. While the 5' regions of both messenger RNAs
      are highly similar, the cpx2 gene has an open-reading frame that could encode a
      new targeting signal. GFP fused with CPX1 localized to the plastids. In contrast,
      the GFP fusion with CPX2 did not target plastids and appeared to localize to
      mitochondria. Both cpx genes are expressed ubiquitously but, based on mutant
      phenotype, they seem to have discrete biological roles. Seedlings homozygous for
      a null mutation in the cpx1 gene completely lack chlorophyll and develop necrotic
      lesions in the light. However, the mutant seedlings and callus cultures will grow
      in tissue culture in the dark, implying that they retain a capacity to produce
      heme. We discuss models for the evolution of the cpx genes and possible roles of
      mitochondrion-localized coprogen oxidase activity in maize.

PMID- 16460506
TI  - Loss of At4 function impacts phosphate distribution between the roots and the
      shoots during phosphate starvation.
AB  - Plants display a range of adaptive responses to phosphate (Pi) starvation
      including an increase in the proportion of Pi allocated to the roots, which
      enhances lateral root development and consequently Pi acquisition. The mechanisms
      by which plants sense Pi and signal Pi reallocation are largely unknown.
      Previously, we cloned At4, a gene predicted to contain multiple short open
      reading frames (ORFs), whose expression is strongly induced by Pi starvation. At4
      is a member of a small gene family whose members, AtIPS1 and two additional genes
      reported here, At4.1 and At4.2, share little conservation among the predicted
      ORFs but high conservation of a 22-nt sequence located in the 3' half of the
      transcript. Here, we show that under Pi-starvation conditions, At4 is expressed
      in the vascular tissue and transcript levels are regulated by both cytokinin and
      ABA. at4, an At4 loss-of-function mutant fails to redistribute Pi to the roots
      correctly in response to Pi deprivation and At4 shoots continue to accumulate a
      greater proportion of Pi relative to wild type. Consistent with this, the primary
      root growth rate in at4 is faster than wild type in low-Pi conditions. The
      conserved sequence found in all members of the At4 gene family hybridizes to a
      small RNA present in Pi-starved roots. These data support a role for At4 in the
      internal allocation of Pi and suggest that the At4 gene is not only subject to Pi
      starvation-inducible expression, but that transcript levels may be adjusted at a
      post-transcriptional level by the activity of an miRNA.

PMID- 16460508
TI  - The autophosphorylated Ser686, Thr688, and Ser689 residues in the intracellular
      juxtamembrane domain of XA21 are implicated in stability control of rice receptor
      like kinase.
AB  - The rice gene Xa21 confers resistance against Xanthomonas oryzae pv. oryzae
      (Xoo). Xa21 encodes a receptor-like kinase (XA21). We demonstrate that XA21
      autophosphorylates residues Ser686, Thr688 and Ser689 in vitro. Substitution of
      these residues with alanines did not affect the autophosphorylation function of
      this kinase, but specifically destabilized the resistance protein in vitro and in
      vivo. Plants carrying these same substitutions in XA21 were compromised in their
      resistance to the normally avirulent Xoo Philippine race 6. Additionally, we show
      that wild-type XA21 and the kinase-dead mutant with the invariable Lys736 residue
      mutated to glutamic acid were also proteolytically degraded in protein extracts.
      Finally, we show a correlation between the in vitro degradation and in vivo
      instability of the proteins. We propose that autophosphorylation of Ser686,
      Thr688 and Ser689 functions to stabilize XA21 against the developmentally
      controlled proteolytic activity.

PMID- 16460509
TI  - The WAG1 and WAG2 protein kinases negatively regulate root waving in Arabidopsis.
AB  - The WAG1 and WAG2 genes of Arabidopsis thaliana encode protein-serine/threonine
      kinases that are closely related to PINOID. In order to determine what roles WAG1
      and WAG2 play in seedling development, we used a reverse genetics approach to
      study the wag1, wag2 and wag1/wag2 mutant phenotypes for clues. Although the wag
      mutants do not contain detectable amounts of the corresponding mRNA, they are
      wild type in most respects. However, wag1/wag2 double mutants exhibit a
      pronounced wavy root phenotype when grown vertically on agar plates, a phenotype
      observed in wild-type plants only on plates inclined to angles less than 90
      degrees. The wag1 and wag2 mutants also demonstrate enhanced root waving, but to
      a lesser extent. Moreover, the double mutant roots are more resistant to the
      effects of N-1-naphthylphthalamic acid on the inhibition of root curling, raising
      the possibility that transport of auxin is affected in the wag mutants. Promoter
      fusions to the gusA reporter gene demonstrate that the WAG promoters are most
      active in root tips, consistent with the observed phenotypes in the wag mutants.

PMID- 16460510
TI  - Arabidopsis CYP90B1 catalyses the early C-22 hydroxylation of C27, C28 and C29
      sterols.
AB  - Arabidopsis dwf4 is a brassinosteroid (BR)-deficient mutant, and the DWF4 gene
      encodes a cytochrome P450, CYP90B1. We report the catalytic activity and
      substrate specificity of CYP90B1. Recombinant CYP90B1 was produced in Escherichia
      coli, and CYP90B1 activity was measured in an in vitro assay reconstituted with
      NADPH-cytochrome P450 reductase. CYP90B1 converted campestanol (CN) to 6
      deoxocathasterone, confirming that CYP90B1 is a steroid C-22 hydroxylase. The
      substrate specificity of CYP90B1 indicated that sterols with a double bond at
      positions C-5 and C-6 are preferred substrates compared with stanols, which have
      no double bond at the position. In particular, the catalytic efficiency
      (k(cat)/K(m)) of CYP90B1 for campesterol (CR) was 325 times greater than that for
      CN. As CR is more abundant than CN in planta, the results suggest that C-22
      hydroxylation of CR before C-5alpha reduction is the main route of BR
      biosynthetic pathway, which contrasts with the generally accepted route via CN.
      In addition, CYP90B1 showed C-22 hydroxylation activity toward various C(27-29)
      sterols. Cholesterol (C27 sterol) is the best substrate, followed by CR (C28
      sterol), whereas sitosterol (C29 sterol) is a poor substrate, suggesting that the
      substrate preference of CYP90B1 may explain the discrepancy between the in planta
      abundance of C27/C28/C29 sterols and C27/C28/C29 BRs.

PMID- 16460511
TI  - Reorganization of the alternative pathways of the Arabidopsis respiratory chain
      by nitrogen supply: opposing effects of ammonium and nitrate.
AB  - The mitochondrial oxidative phosphorylation system in plants possesses a variety
      of alternative pathways that decrease respiratory ATP production. These
      alternative pathways are mediated by three classes of bypass proteins: the type
      II NAD(P)H dehydrogenases (which circumvent complex I of the electron transport
      chain), the alternative oxidases (AOXs; which circumvent complexes III and IV)
      and the uncoupling proteins (which circumvent ATP synthase). We have monitored
      the expression of all genes encoding respiratory bypass proteins in Arabidopsis
      thaliana growing with different sources of inorganic nitrogen (N). Resupply of
      nitrate (NO) to N-limited seedling cultures caused a decrease in the transcript
      abundance of several type II NAD(P)H dehydrogenase and AOX genes, while resupply
      of ammonium (NH) led to broad increases in expression in the same gene families.
      Similar results were observed upon switching between nitrate and ammonium in the
      absence of N stress. Nitrate signalling was found to be mediated primarily by the
      nitrate ion itself, whereas ammonium regulation was dependent upon assimilation
      and affected by changes in apoplastic pH. Corresponding alterations in
      alternative respiratory pathway capacities were apparent in seedlings supplied
      with either nitrate or ammonium as an N source and in mitochondria purified from
      the seedlings. Specifically, AOX capacity and protein abundance, as well as
      calcium-dependent external NADH oxidation, were substantially elevated after
      growth on ammonium. The increased capacity of respiratory bypass pathways after
      switching from nitrate to ammonium was correlated to an overall respiratory
      increase.

PMID- 16460512
TI  - Molecular cloning and characterization of Arabidopsis thaliana Golgi alpha
      mannosidase II, a key enzyme in the formation of complex N-glycans in plants.
AB  - N-glycosylation is one of the major post-translational modifications of proteins
      in eukaryotes; however, the processing reactions of oligomannosidic N-glycan
      precursors leading to hybrid-type and finally complex-type N-glycans are not
      fully understood in plants. To investigate the role of Golgi alpha-mannosidase II
      (GMII) in the formation of complex N-glycans in plants, we identified a putative
      GMII from Arabidopsis thaliana (AtGMII; EC 3.2.1.114) and characterized the
      enzyme at a molecular level. The putative AtGMII cDNA was cloned, and its deduced
      amino acid sequence revealed a typical type II membrane protein of 1173 amino
      acids. A soluble recombinant form of the enzyme produced in insect cells was
      capable of processing different physiologically relevant hybrid N-glycans.
      Furthermore, a detailed N-glycan analysis of two AtGMII knockout mutants revealed
      the predominant presence of unprocessed hybrid N-glycans. These results provide
      evidence that AtGMII plays a central role in the formation of complex N-glycans
      in plants. Furthermore, conclusive evidence was obtained that alternative routes
      in the conversion of hybrid N-glycans to complex N-glycans exist in plants.
      Transient expression of N-terminal AtGMII fragments fused to a GFP reporter
      molecule demonstrated that the transmembrane domain and 10 amino acids from the
      cytoplasmic tail are sufficient to retain a reporter molecule in the Golgi
      apparatus and that lumenal sequences are not involved in the retention mechanism.
      A GFP fusion construct containing only the transmembrane domain was predominantly
      retained in the ER, a result that indicates the presence of a motif promoting ER
      export within the last 10 amino acids of the cytoplasmic tail of AtGMII.

PMID- 16460513
TI  - Distinct and overlapping roles of two gibberellin 3-oxidases in Arabidopsis
      development.
AB  - Gibberellin (GA) 3-oxidase, a class of 2-oxoglutarate-dependent dioxygenases,
      catalyzes the conversion of precursor GAs to their bioactive forms, thereby
      playing a direct role in determining the levels of bioactive GAs in plants.
      Gibberellin 3-oxidase in Arabidopsis is encoded by a multigene family consisting
      of at least four members, designated AtGA3ox1 to AtGA3ox4. It has yet to be
      investigated how each AtGA3ox gene contributes to optimizing bioactive GA levels
      during growth and development. Using quantitative real-time PCR analysis, we have
      shown that each AtGA3ox gene exhibits a unique organ-specific expression pattern,
      suggesting distinct developmental roles played by individual AtGA3ox members. To
      investigate the sites of synthesis of bioactive GA in plants, we generated
      transgenic Arabidopsis that carried AtGA3ox1-GUS and AtGA3ox2-GUS fusions.
      Comparisons of the GUS staining patterns of these plants with that of AtCPS-GUS
      from previous studies revealed the possible physical separation of the early and
      late stages of the GA pathway in roots. Phenotypic characterization and
      quantitative analysis of the endogenous GA content of ga3ox1 and ga3ox2 single
      and ga3ox1/ga3ox2 double mutants revealed distinct as well as overlapping roles
      of AtGA3ox1 and AtGA3ox2 in Arabidopsis development. Our results show that
      AtGA3ox1 and AtGA3ox2 are responsible for the synthesis of bioactive GAs during
      vegetative growth, but that they are dispensable for reproductive development.
      The stage-specific severe GA-deficient phenotypes of the ga3ox1/ga3ox2 mutant
      suggest that AtGA3ox3 and AtGA3ox4 are tightly regulated by developmental cues;
      AtGA3ox3 and AtGA3ox4 are not upregulated to compensate for GA deficiency during
      vegetative growth of the double mutant.

PMID- 16460514
TI  - Arabidopsis CDKA;1, a cdc2 homologue, controls proliferation of generative cells
      in male gametogenesis.
AB  - The protein kinase cdc2 is conserved throughout eukaryotes and acts as a key
      regulator of the cell cycle. In plants, A-type cyclin-dependent kinase (CDKA), a
      homologue of cdc2, has a role throughout the cell cycle. Here we show that a loss
      of-function mutation in CDKA;1, encoding the only Arabidopsis CDKA, results in
      lethality of the male gametophyte. Heterozygous plants produced mature siliques
      containing about 50% aborted seeds, and segregation distortion was observed in
      paternal inheritance. Microspores normally undergo an asymmetric cell division,
      pollen mitosis I (PMI), to produce bicellular pollen grains. The larger
      vegetative cell does not divide, but the smaller generative cell undergoes
      mitosis, PMII, to form the two sperm cells, thereby generating tricellular pollen
      grains. The cdka-1 mutant, however, produces mature bicellular pollen grains,
      consisting of a single sperm-like cell and a vegetative cell, due to failure of
      PMII. The mutant sperm-like cell is fertile, and preferentially fuses with the
      egg cell to initiate embryogenesis. As the central cell nucleus remains
      unfertilized, however, double fertilization does not occur. In heterozygous
      plants, the embryo is arrested at the globular stage, most likely because of loss
      of endosperm development, whereas it is arrested at the one- or two-cell stage in
      presumptive homozygous plants. Thus, CDKA;1 is essential for cell division of the
      generative cell in male gametogenesis.

PMID- 16460516
TI  - A high-throughput screen for genes from castor that boost hydroxy fatty acid
      accumulation in seed oils of transgenic Arabidopsis.
AB  - It is desirable to produce high homogeneity of novel fatty acids in oilseeds
      through genetic engineering to meet the increasing demands of the oleo-chemical
      industry. However, expression of key enzymes for biosynthesis of industrial fatty
      acids usually results in low levels of desired fatty acids in transgenic
      oilseeds. The abundance of derivatized fatty acids in their natural species
      suggests that additional genes are needed for high production in transgenic
      plants. We used the model oilseed plant Arabidopsis thaliana expressing a castor
      fatty acid hydroxylase (FAH12) to identify genes that can boost hydroxy fatty
      acid accumulation in transgenic seeds. Here we describe a high-throughput
      approach that, in principle, can allow testing of the entire transcriptome of
      developing castor seed endosperm by shotgun transforming a full-length cDNA
      library into an FAH12-expressing Arabidopsis line. The resulting transgenic seeds
      were screened by high-throughput gas chromatography. We obtained several lines
      transformed with castor cDNAs that contained increased amounts of hydroxy fatty
      acids in transgenic Arabidopsis. These cDNAs were then isolated by PCR and
      retransformed into the FAH12-expressing line, thus confirming their beneficial
      contributions to hydroxy fatty acid accumulation in transgenic Arabidopsis seeds.
      Although we describe an approach that is targeted to oilseed engineering, the
      methods we developed can be applied in many areas of plant biotechnology and
      functional genomic research.

PMID- 16460517
TI  - Direct labelling of BAC-DNA by rolling-circle amplification.
AB  - Efficient amplification and labelling of probes are crucial for successful
      sequence detection by fluorescent in situ hybridization (FISH). In particular,
      chromosome painting to visualize chromosome segments or entire chromosomes by
      FISH requires large amounts of probes derived from extended templates. There are
      a number of techniques for probe labelling. The most widespread is nick
      translation, based on the replicational incorporation of modified nucleotides.
      Here we demonstrate successful rolling-circle amplification (RCA) of very low
      amounts of long circular template sequences (single bacterial artificial
      chromosomes (BACs) or pools of BACs). The amplicons were suitable for labelling
      by nick translation and subsequent FISH. A novel achievement is the use of RCA
      for simultaneous amplification and labelling of single BACs or BAC pools in a
      labour- and cost-effective manner.

PMID- 16460515
TI  - The 3' untranslated region of a soybean cytosolic glutamine synthetase (GS1)
      affects transcript stability and protein accumulation in transgenic alfalfa.
AB  - Higher plants assimilate nitrogen in the form of ammonia through the concerted
      activity of glutamine synthetase (GS) and glutamate synthase (GOGAT). The GS
      enzyme is either located in the cytoplasm (GS1) or in the chloroplast (GS2).
      Glutamine synthetase 1 is regulated in different plants at the transcriptional
      level and there are some reports of regulation at the level of protein stability.
      Here we present data that clearly establish that GS1 in plants is also regulated
      at the level of transcript turnover and at the translational level. Using a
      Glycine max (soybean) GS1 transgene, with and without its 3' untranslated region
      (UTR), driven by the constitutive CaMV 35S promoter in Medicago sativa (alfalfa)
      and Nicotiana tabacum (tobacco), we show that the 3' UTR plays a major role in
      both transcript turnover and translation repression in both the leaves and the
      nodules. Our data suggest that the 3' UTR mediated turnover of the transcript is
      regulated by a nitrogen metabolite or carbon/nitrogen ratios. We also show that
      the 3' UTR of the gene for the soybean GS1 confers post-transcriptional
      regulation on a reporter gene. Our dissection of post-transcriptional and
      translational levels of regulation of GS in plants shows that the situation in
      plants strongly resembles that in other organisms where GS is regulated at almost
      all levels. Multistep regulation of GS shows the high priority given by organisms
      to regulating and ensuring optimal control of nitrogen substrates and preventing
      overproduction of glutamine and drainage of the glutamate pool.

PMID- 16460518
TI  - Validation of RNAi silencing specificity using synthetic genes: salicylic acid
      binding protein 2 is required for innate immunity in plants.
AB  - RNA interference (RNAi) is widely used to specifically silence the expression of
      any gene to study its function and to identify and validate therapeutic targets.
      Despite the popularity of this technology, recent studies have shown that RNAi
      may also silence non-targeted genes. Here we demonstrate the utility of a quick,
      efficient and robust approach to directly validate the specificity of RNAi as an
      alternative to indirect validation of RNAi through gene expression profiling. Our
      approach involves reversing (complementing) the RNAi-induced phenotype by
      introducing a synthetic version of the target gene that is designed to escape
      silencing. This synthetic gene complementation approach can also be used for
      mutational analysis of the target gene, or to provide a functional version of a
      defective protein after silencing the defective gene by RNAi. Using this approach
      we demonstrate that the loss of systemic acquired resistance, a form of innate
      immunity in plants, is indeed due to the silencing of salicylic acid-binding
      protein 2 rather than to off-target effects.

PMID- 16460521
TI  - Promoting transfer: effects of self-explanation and direct instruction.
AB  - Explaining new ideas to oneself can promote transfer, but how and when such self
      explanation is effective is unclear. This study evaluated whether self
      explanation leads to lasting improvements in transfer success and whether it is
      more effective in combination with direct instruction or invention. Third-
      through fifth-grade children (ages 8-11; n=85) learned about mathematical
      equivalence under one of four conditions varying in (a) instruction on versus
      invention of a procedure and (b) self-explanation versus no explanation. Both
      self-explanation and instruction helped children learn and remember a correct
      procedure, and self-explanation promoted transfer regardless of instructional
      condition. Neither manipulation promoted greater improvements on an independent
      measure of conceptual knowledge. Microgenetic analyses provided insights into
      potential mechanisms underlying these effects.

PMID- 16460522
TI  - Children's use of syntactic and pragmatic knowledge in the interpretation of
      novel adjectives.
AB  - In Study 1, English-speaking 3- and 4-year-olds heard a novel adjective used to
      label one of two objects and were asked for the referent of a different novel
      adjective. Children were more likely to select the unlabeled object if the two
      adjectives appeared prenominally (e.g., "a very DAXY dog") than as predicates
      (e.g., "a dog that is very DAXY"). Study 2 revealed that this response occurred
      only when both adjectives were prenominal. Study 3 replicated Study 1 with Hebrew
      speaking 3- and 4-year-olds, even though in Hebrew both types of adjectives
      appear postnominally. Preschoolers understand that prenominal adjectives imply a
      restriction of the reference of nouns, and this knowledge motivates a contrastive
      pragmatic inference regarding the referents of different prenominal adjectives.

PMID- 16460523
TI  - Marital conflict and disruption of children's sleep.
AB  - Marital conflict was examined as a predictor of the quality and quantity of sleep
      in a sample of healthy 8- to 9-year-olds. Parents and children reported on
      marital conflict, the quantity and quality of children's sleep were examined
      through an actigraph worn for 7 consecutive nights, and child sleepiness was
      derived from child and mother reports. Increased marital conflict was associated
      with disruptions in the quantity and quality of children's sleep as well as
      subjective sleepiness, even after controlling for child age, ethnic group
      membership, socioeconomic status, sex, and body mass index. The results support
      the sensitization hypothesis in that exposure to marital conflict may influence
      an important facet of children's biological regulation, namely sleep.

PMID- 16460524
TI  - Untangling the links of parental responsiveness to distress and warmth to child
      outcomes.
AB  - This study demonstrated separate linkages between 2 features of positive
      parenting--responsiveness to distress and warmth--and different aspects of
      children's socio-emotional functioning, in a sample of 106 children (6-8 years
      old). As expected, mothers' and fathers' responsiveness to distress, but not
      warmth, predicted better negative affect regulation. Maternal responsiveness to
      distress also predicted children's empathy and prosocial responding. Maternal
      warmth, but not responsiveness to distress, was linked to better regulation of
      positive affect and (in boys only) to greater peer acceptance. Additionally,
      negative affect regulation mediated between maternal responsiveness to distress
      and children's empathic responding. Positive affect regulation mediated between
      maternal warmth and boys' peer acceptance. The findings support a differentiated
      approach to positive parenting.

PMID- 16460525
TI  - An experimental manipulation of retrospectively defined earned and continuous
      attachment security.
AB  - Recent longitudinal data suggest that retrospectively defined earned-secures are
      not more likely than continuous-secures to have been anxiously attached to their
      mothers in infancy and indeed experience high-quality maternal parenting in
      childhood. Such findings leave unanswered the question of why earned-secures
      report negative childhood experiences. On the basis of speculation that earned
      security may result from depression-related biases in the recall of early
      experiences, this report describes the effects of an experimental mood induction
      on the valence of young adults' (18-25 years) life narratives as assessed in the
      Adult Attachment Interview. Among secure adults, individuals in a sadness
      condition were more likely to be classified as earned-secure; happy participants
      were more likely to be classified as continuous-secure. Induced mood was
      unrelated to security versus insecurity.

PMID- 16460527
TI  - Learning from falling.
AB  - Walkers fall frequently, especially during infancy. Children (15-, 21-, 27-, 33-,
      and 39-month-olds) and adults were tested in a novel foam pit paradigm to examine
      age-related changes in the relationship between falling and prospective control
      of locomotion. In trial 1, participants walked and fell into a deformable foam
      pit marked with distinct visual cues. Although children in all 5 age groups
      required multiple trials to learn to avoid falling, the number of children who
      showed adult-like, 1-trial learning increased with age. Exploration and
      alternative locomotor strategies increased dramatically on learning criterion
      trials and displays of negative affect were limited. Learning from falling is
      discussed in terms of the immediate and long-term effects of falling on
      prospective control of locomotion.

PMID- 16460526
TI  - Revisiting the association between reading achievement and antisocial behavior:
      new evidence of an environmental explanation from a twin study.
AB  - Previous studies have reported, but not explained, the reason for a robust
      association between reading achievement and antisocial behavior. This association
      was investigated using the Environmental Risk (E-Risk) Longitudinal Twin Study, a
      nationally representative 1994-1995 birth cohort of 5- and 7-year-olds. Results
      showed that the association resulted primarily from environmental factors common
      to both reading and antisocial behavior and was stronger in boys. Environmental
      factors also explained the relation between reading disability and conduct
      disorder. Leading candidate environmental risk factors weakly mediated the
      association. For boys the best explanation was a reciprocal causation model: poor
      reading led to antisocial behavior, and vice versa. In contrast, the relation
      between reading achievement and attention deficit hyperactivity disorder was best
      explained by common genetic influences.

PMID- 16460528
TI  - Contemporaneous and longitudinal associations between social behavior and
      literacy achievement in a sample of low-income elementary school children.
AB  - This study investigates associations between social skills (aggression and
      prosocial behavior) and literacy achievement in a sample of low-income children
      (between 4 and 6 years old when the study began) during elementary school.
      Results revealed consistent associations between social skills and literacy
      achievement in the first, third, and fifth grades, but the patterns of the
      associations were different for aggression and prosocial behavior. While the
      strength of the association between aggression and literacy achievement increased
      over the elementary grades, the association between prosocial behavior and
      literacy achievement decreased. In addition, path analyses revealed that poor
      literacy achievement in the first and third grades predicted relatively high
      aggressive behavior in the third and fifth grades, respectively.

PMID- 16460529
TI  - Environmental control, social context, and individual differences in behavioral
      and cortisol responses to novelty in infant rhesus monkeys.
AB  - The effects of appetitive controllability on behavioral and cortisol reactivity
      to novelty in 12 infant rhesus monkeys were studied. Surrogate-peer-reared
      infants had homecage access to food treats contingently via lever pressing
      ("master") or noncontingently ("yoked") for 12 weeks from postnatal month 2.
      Masters lever-pressed more, but did not differ in baseline cortisol. At month 5,
      infants were exposed to a novel environment in social groups and individually.
      Masters were significantly more active and exhibited significantly lower cortisol
      reactivity to the novel environment, but only in the individual context. Also,
      individual differences in operant behavior were positively correlated with
      behavioral activity and negatively correlated with cortisol reactivity to the
      novel environment. The results reveal context-specific benefits of contingent
      stimulation in infancy.

PMID- 16460530
TI  - Interparental discord and child adjustment: prospective investigations of
      emotional security as an explanatory mechanism.
AB  - Advancing the process-oriented study of links between interparental discord and
      child adjustment, 2 multimethod prospective tests of emotional security as an
      explanatory mechanism are reported. On the basis of community samples, with waves
      spaced 2 years apart, Study 1 (113 boys and 113 girls, ages 9-18) identified
      emotional security as a mediator in a 2-wave test, whereas Study 2 (105 boys and
      127 girls, ages 5-7) indicated emotional security as an intervening mechanism in
      a 3-wave test. Relations between discord and emotional security increased as
      children moved into adolescence in Study 1. Emotional security was identified as
      an explanatory mechanism for both internalizing and externalizing problems in
      children.

PMID- 16460531
TI  - Number sense growth in kindergarten: a longitudinal investigation of children at
      risk for mathematics difficulties.
AB  - Number sense development of 411 middle- and low-income kindergartners (mean age
      5.8 years) was examined over 4 time points while controlling for gender, age, and
      reading skill. Although low-income children performed significantly worse than
      middle-income children at the end of kindergarten on all tasks, both groups
      progressed at about the same rate. An exception was story problems, on which the
      low-income group achieved at a slower rate; both income groups made comparable
      progress when the same problems were presented nonverbally with visual referents.
      Holding other predictors constant, there were small but reliable gender effects
      favoring boys on overall number sense performance as well as on nonverbal
      calculation. Using growth mixture modeling, 3 classes of growth trajectories in
      number sense emerged.

PMID- 16460532
TI  - Mirror self-recognition beyond the face.
AB  - Three studies (N=144) investigated how toddlers aged 18 and 24 months pass the
      surprise-mark test of self-recognition. In Study 1, toddlers were surreptitiously
      marked in successive conditions on their legs and faces with stickers visible
      only in a mirror. Rates of sticker touching did not differ significantly between
      conditions. In Study 2, toddlers failed to touch a sticker on their legs that had
      been disguised before being marked. In Study 3, having been given 30-s exposure
      to their disguised legs before testing, toddlers touched the stickers on their
      legs and faces at equivalent levels. These results suggest that toddlers pass the
      mark test based on expectations about what they look like, expectations that are
      not restricted to the face.

PMID- 16460533
TI  - Development of displaced speech in early mother-child conversations.
AB  - This study documents the development of symbolic, spatial, and temporal
      displacement of toddler's speech. Fifty-six children and their mothers were
      observed longitudinally 5 times from 18 to 30 months of age during a staged
      communication play while they engaged in scenes that encouraged interacting,
      requesting, and commenting and scenes that explicitly focused on the past and the
      future. Reliably coded transcripts revealed that toddlers highlighted symbols at
      a high and stable rate and that over time they became less focused on the here
      and now and more focused on internal states. The greatest expansion was into the
      near future. Only in scenes designed to discuss the past and future did
      conversations turn to the past and expand spatially beyond here.

PMID- 16460534
TI  - Disclosure and secrecy in adolescent-parent relationships.
AB  - Beliefs about parents' legitimate authority and adolescents' obligations to
      disclose to parents and actual disclosure and secrecy in different domains were
      examined in 276 ethnically diverse, lower middle-class 9th and 12th graders
      (Ms=14.62 and 17.40 years) and their parents (n=249). Adolescents were seen as
      more obligated to disclose prudential issues and less obligated to disclose
      personal than moral, conventional, and multifaceted issues; parents viewed
      adolescents as more obligated to disclose to parents than adolescents perceived
      themselves to be. Adolescents disclosed more to mothers than to fathers,
      particularly regarding personal issues, but mothers overestimated girls'
      disclosure. Greater trust, perceived obligations to disclose, and, for personal
      issues, more parental acceptance and psychological control predicted more
      disclosure and less secrecy.

PMID- 16460535
TI  - Child adaptational development in contexts of interparental conflict over time.
AB  - This multi-method study sought to identify parameters of developmental change and
      stability of child reaction patterns to interparental conflict in the context of
      family relations in a sample of 223 6-year-old children and their parents
      followed over the course of one year. Consistent with the sensitization
      hypothesis, interparental withdrawal and hostility each consistently and uniquely
      predicted child distress reactions to conflict even after analytically
      controlling for parental warmth. Associations were found across multiple domains
      of child responding (i.e., overt negative affect, subjective negative affect,
      internal representations) and both concurrent and prospective, autoregressive
      analyses. Results of the autoregressive path analyses indicated moderate
      stability in each of the domains of conflict reactivity over the 1-year
      longitudinal period.

PMID- 16460536
TI  - Recognizing the face of Johnny, Suzy, and me: insensitivity to the spacing among
      features at 4 years of age.
AB  - Four-year-olds were tested for their ability to use differences in the spacing
      among features to recognize familiar faces. They were given a storybook depicting
      multiple views of 2 children. They returned to the laboratory 2 weeks later and
      used a "magic wand" to play a computer game that tested their ability to
      recognize the familiarized faces and their own face based on the spacing of
      features. Children performed at chance levels. Follow-up studies confirmed that
      they had attended to internal facial features and validated the stimuli. The
      results contrast with studies showing some sensitivity to the spacing of features
      in infants and preschool children; multiple mechanisms of face processing may
      make use of spatial relations and develop at different rates.

PMID- 16460539
TI  - Prevalence surveys of healthcare-associated infections: what do they tell us, if
      anything?
AB  - Prevalence surveys of healthcare-associated infections offer advantages over
      incidence surveys, including the relative ease of performance, a reduced
      requirement for resources, the ability to include increased numbers of hospitals
      within a shorter period of time, and the possibility of more rapid data analysis
      and feedback. Prevalence surveys have also been shown to be useful in monitoring
      the effectiveness of infection control programmes. Prevalence surveys appear to
      be desirable when financial support, and/or the will to carry out incidence
      surveys, is lacking. However, it is imperative that prevalence surveys use
      standardised methodology and internationally recognised definitions of infection.

PMID- 16460540
TI  - Evolving trends in infective endocarditis.
AB  - Infective endocarditis is a microbial infection of the endocardial surface and,
      despite improvements in diagnostic accuracy, medical therapy and surgical
      techniques, mortality remains high. This review focuses on changes in
      epidemiology, microbiology and diagnosis, as well as changes in medical and
      surgical management of infective endocarditis affecting native and prosthetic
      valves in adults, that have evolved during the past two decades. Significant
      changes have included an increasing involvement of prosthetic valves and
      nosocomially-acquired disease, an increased involvement of staphylococci as the
      causative agents, and a recognition that elderly individuals with degenerative
      valvular disease are the most vulnerable population. Topics still requiring study
      include whether and when valve replacement should be performed, and how to
      predict perivalvular complications or embolisation based on echocardiography
      findings. Optimisation of antimicrobial treatment schemes (choice of the
      antibiotic, dose and duration) also requires further investigation.

PMID- 16460541
TI  - Outcome of inappropriate empirical antibiotic therapy in patients with
      Staphylococcus aureus bacteraemia: analytical strategy using propensity scores.
AB  - Patients with Staphylococcus aureus bacteraemia (SAB) who received either
      inappropriate or appropriate empirical therapy were compared by using two risk
      stratification models: (1) a cohort study using a propensity score to adjust for
      confounding by empirical treatment assignment; and (2) a propensity-matched case
      control study. Inappropriate empirical therapy was modelled on the basis of
      patient characteristics, and included in the multivariate model to adjust for
      confounding. For case-matching analysis, patients with inappropriate empirical
      therapy (cases) were matched to those with appropriate empirical therapy
      (controls) on the basis of the propensity score (within 0.03 on a scale of 0-1).
      In total, 238 patients with SAB were enrolled in the cohort study.
      Characteristics associated with inappropriate empirical therapy were methicillin
      resistance, underlying haematological malignancy, no history of colonisation with
      methicillin-resistant S. aureus, and a long hospital stay before SAB. These
      variables were included in the propensity score, which had an area under the
      receiver operating characteristics curve of 85%. In the cohort study, SAB-related
      mortality was 39% (45/117) for inappropriate empirical therapy vs. 28% (34/121)
      for appropriate empirical therapy (odds ratio (OR) 1.60; 95% CI 0.93-2.76). After
      adjustment for independent predictors for mortality and the propensity score,
      inappropriate empirical therapy was not associated with mortality (adjusted OR
      1.39; 95% CI 0.62-3.15). In the matched case-control study (50 pairs), SAB
      related mortality was 32% (16/50) for inappropriate empirical therapy and 28%
      (14/50) for appropriate empirical therapy (McNemar's test; p 0.85; OR 1.15; 95%
      CI 0.51-2.64). In conclusion, inappropriate empirical therapy resulted in only a
      slight tendency towards increased mortality in patients with SAB.

PMID- 16460543
TI  - Spread of Staphylococcus aureus clinical isolates carrying Panton-Valentine
      leukocidin genes during a 3-year period in Greece.
AB  - Three collections of Staphylococcus aureus isolates (n = 1,058) were investigated
      to assess the spread of Panton-Valentine leukocidin (PVL)-producing strains in
      Greece and their association with skin and soft-tissue infections (SSTIs). The
      isolates were collected during 2001-2003 from inpatients and outpatients with
      invasive infections in two distinct geographical areas. Clonal types were
      identified according to their ClaI-mecA::ClaI-Tn554::pulsed-field gel
      electrophoresis patterns, and the presence of the lukS-PV and lukF-PV genes was
      assessed by PCR. In total, 287 (27%) S. aureus isolates carried the PVL genes:
      45% of methicillin-resistant S. aureus (MRSA) and 12% of methicillin-sensitive S.
      aureus (MSSA). All the PVL-positive MRSA isolates belonged to a single clone that
      was disseminated in the community and hospitals. The PVL-positive MSSA isolates
      were polyclonal, with 14 of 65 isolates being associated with hospital-acquired
      infections. The community-acquired isolates were from SSTIs, while the hospital
      acquired isolates were associated with surgical wound infections, especially
      those involving prosthetic devices. Thus, a unique clone of PVL-positive MRSA has
      spread in both the community and the hospital setting in Greece, and has replaced
      older clonal types.

PMID- 16460542
TI  - Molecular characterisation of a dominant methicillin-resistant Staphylococcus
      aureus (MRSA) clone in a Mexican hospital (1999-2003).
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 216), collected
      between January 1999 and May 2003 in a tertiary-care university hospital in
      Guadalajara, Mexico, were characterised by antibiotype, pulsed-field gel
      electrophoresis (PFGE) of SmaI macrorestriction fragments, and hybridisation of
      ClaI digests with mecA- and Tn554-specific DNA probes. Representatives of the
      single clonal type found were analysed by spa typing, multilocus sequence typing
      and staphylococcal chromosomal cassette mec (SCCmec) typing, and were tested for
      the presence of 22 virulence determinants and agr type. A single PFGE pattern was
      identified, with minor variations over time, with spa type 2, sequence type 5,
      SCCmec type II, agr type 2 and the presence of the enterotoxin genes seg and sei,
      the gamma-haemolysin variant gene hlg-v and the leukocidin lukE-lukD genes. In
      addition, the isolates showed antimicrobial resistance to beta-lactams,
      macrolides, chloramphenicol and imipenem, and susceptibility to gentamicin,
      rifampicin, trimethoprim-sulphamethoxazole and vancomycin. Following its
      appearance in 1997, this clone spread within the hospital, and is now present in
      most of the hospital units and wards.

PMID- 16460544
TI  - Use of surveillance cultures and enteral vancomycin to control methicillin
      resistant Staphylococcus aureus in a paediatric intensive care unit.
AB  - This study assessed the effects of throat and gut surveillance, combined with
      enteral vancomycin, on gut overgrowth, transmission of methicillin-resistant
      Staphylococcus aureus (MRSA), infections and mortality in patients admitted to a
      paediatric intensive care unit (PICU). A 4-year prospective observational study
      was undertaken with 1241 children who required ventilation for >or=4 days.
      Patients identified as MRSA carriers following surveillance cultures of throat
      and rectum received enteral vancomycin. Twenty-nine (2.4%) children carried MRSA,
      19 on admission and nine during treatment in the PICU; one patient was not able
      to be evaluated. Overgrowth was present in 22 (75%) of the carriers. Ten (0.8%)
      children developed 21 MRSA infections (15 exogenous infections in eight children
      at a median of 8 days (IQR 3-10.5); five primary endogenous infections at a
      median of 3 days (IQR 1-25) in three children when they were in overgrowth
      status; one child developed both types of infection). Enteral vancomycin reduced
      gut overgrowth significantly, completely preventing secondary endogenous
      infections. Transmission occurred on nine occasions over a period of 4 years.
      Four patients died, two (5.9%) with MRSA infection, giving a mortality (11.8%)
      similar to the study population (9.8%). No emergence of vancomycin-resistant
      enterococci or S. aureus with intermediate susceptibility to vancomycin was
      detected. A policy based on throat and gut surveillance, combined with enteral
      vancomycin, for critically-ill children who were MRSA carriers was found to be
      effective and safe, and challenges the recommended guidelines of nasal swabbing
      followed by topical mupirocin.

PMID- 16460545
TI  - Staphylococcus lugdunensis: clinical spectrum, antibiotic susceptibility, and
      phenotypic and genotypic patterns of 39 isolates.
AB  - Staphylococcus lugdunensis is a member of the coagulase-negative staphylococci
      with the potential to cause clinically significant infections. The spectrum of
      infections was investigated in 39 isolates of S. lugdunensis from 38 patients.
      Most (73%) infections were located below the waist, while those above the waist
      were mainly (5/7) breast abscesses. Most isolates were susceptible to the
      antibiotics tested, although 15.4% were beta-lactamase-positive and could be
      identified by the disk-diffusion method for penicillin G. There was very good
      concordance between the disk-diffusion method and the Etest method for oxacillin
      resistance. Pulsed-field gel electrophoresis (PFGE) showed that 56% of the
      isolates belonged to one SmaI pulsotype, while phenotypic analysis by the Phene
      Plate system identified three main phenotypic groups. Although the S. lugdunensis
      isolates analysed were obtained from different patients, treated in different
      wards and hospitals during a 4-year period, there was a low degree of diversity,
      both genotypically and phenotypically. For this reason, PFGE is not suitable for
      the analysis of an outbreak situation, and the homogeneity observed may indicate
      that S. lugdunensis is a genetically conserved species of coagulase-negative
      Staphylococcus.

PMID- 16460546
TI  - Serotypes of carriage and invasive isolates of Streptococcus pneumoniae in
      Brazilian children in the era of pneumococcal vaccines.
AB  - Nasopharyngeal carriage of Streptococcus pneumoniae is a key factor in the
      development of invasive disease and the spread of resistant strains within the
      community. A single nasopharyngeal swab was obtained from 648 unvaccinated
      children aged <5 years, either healthy or with acute respiratory tract infection
      or meningitis, during the winters of 2000 and 2001. The overall pneumococcal
      carriage rate was 35.8% (95% CI 32.1-39.6). The pneumococcal serotypes found most
      frequently in the nasopharynx were 14, 6B, 6A, 19F, 10A, 23F and 18C, which
      included five of the seven serotypes in the currently licensed seven-valent
      conjugate vaccine (PCV7); serotypes 4 and 9V were less common. Serotypes 1 and 5
      were isolated rarely from the nasopharynx. A comparison of 222 nasopharyngeal
      isolates with 125 invasive isolates, matched for age and time to the carrier
      isolates, showed a similar prevalence of penicillin non-susceptible pneumococci
      (PNSp) (19.8% and 19.2%, respectively). PNSp serotypes were similar (6B, 14, 19F,
      19 A, 23B and 23F) for carriage and invasive disease isolates. The coverage of
      PCV7 for carriage isolates (52.2%) and invasive isolates (62.4%) did not differ
      significantly (p 0.06); similarly, there was no significant difference in PCV7
      coverage for carriage isolates (34.5%) and invasive isolates (28.2%) of PNSp.
      These data suggest that PCV7 has the potential to reduce pneumococcal carriage
      and the number of carriers of PNSp belonging to vaccine serotypes.

PMID- 16460547
TI  - High-dose cefepime as an alternative treatment for infections caused by TEM-24
      ESBL-producing Enterobacter aerogenes in severely-ill patients.
AB  - This study evaluated retrospectively the efficacy of treatment with cefepime vs.
      a carbapenem, in combination with amikacin or ciprofloxacin, for seriously-ill
      patients infected with ESBL-producing Enterobacter aerogenes who were admitted to
      an intensive care unit. Forty-four episodes of infection were investigated in 43
      patients: 21 treated with cefepime; 23 with a carbapenem. The two treatment
      groups did not differ statistically in terms of age, APACHE II scores, and
      infection sites, but the average duration of antibiotic exposure was
      significantly shorter in the cefepime group (8.5 days vs. 11.4 days; p 0.04).
      Clinical improvement was seen in 62% of patients receiving cefepime vs. 70% of
      patients receiving a carbapenem (p 0.59). Bacteriological eradication was
      achieved in 14% of patients receiving cefepime vs. 22% of patients receiving a
      carbapenem (p 0.76). The 30-day mortality rates related to infection were 33% in
      the cefepime group and 26% in the carbapenem group (p 0.44). Thus, outcome
      parameters did not differ significantly between the two groups. Nevertheless, a
      statistically significant increase in failure to eradicate ESBL-producing E.
      aerogenes was observed as the MICs of cefepime rose (p 0.017). Pulsed-field gel
      electrophoresis revealed three distinct clones, but one predominant clone
      harbouring the bla(TEM-24) gene was associated with most (42/44) of the episodes
      of infection. It was concluded that cefepime may be an alternative agent for
      therapy of severe infections caused by TEM-24 ESBL-producing E. aerogenes,
      although further studies are required to confirm these observations.

PMID- 16460548
TI  - Pandrug-resistant Pseudomonas aeruginosa among hospitalised patients: clinical
      features, risk-factors and outcomes.
AB  - Between 1 January 2003 and 31 December 2003, 37 patients had positive cultures of
      pandrug-resistant Pseudomonas aeruginosa (PDRPA) resistant to all commercially
      available anti-pseudomonal antimicrobial agents in Taiwan, including anti
      pseudomonal penicillins, ceftazidime, fourth-generation cephalosporins,
      aztreonam, carbapenems, aminoglycosides and ciprofloxacin. Nineteen (51.4%)
      patients had PDRPA infections, including pneumonia (17 patients), catheter
      related bacteraemia (one patient) and anal abscess (one patient). Eighteen
      patients were classified as having PDRPA colonisation, based on absence of
      clinical signs or symptoms of infection. In total, 92 isolates were recovered
      from various specimens, with the majority (85.9%) recovered from respiratory
      tract secretions (sputa, bronchial washings and pleural effusions), followed by
      urine (4.3%) and catheter tips (3.3%). Twenty-eight (75.7%) patients yielded
      cultures of non-PDR P. aeruginosa isolates before isolation of PDRPA, with a mean
      period between the first isolation of non-PDR P. aeruginosa and the isolation of
      PDRPA of 128.3 days. Most patients had received beta-lactam antibiotics,
      fluoroquinolones or carbapenems for prolonged periods. Univariate analysis showed
      that PDRPA infection, male gender and the presence of fever at the time of PDRPA
      isolation were associated with increased mortality.

PMID- 16460549
TI  - Risk groups for clinical complications of norovirus infections: an outbreak
      investigation.
AB  - Norovirus infections have been described as self-limiting diseases of short
      duration. An investigation of a norovirus outbreak in a university hospital
      provided evidence for severe clinical features in patients with several
      underlying diseases. Clinical outcomes of norovirus infection were defined. Risk
      factor analysis targeting underlying diseases and medication was performed using
      multivariate analyses. In five outbreak wards, 84 patients and 60 nurses were
      infected (an overall attack rate of 32% in patients, and 76% in nurses). The
      causative agent was the new variant Grimsby virus. Severe clinical features,
      including acute renal failure, arrhythmia and signs of acute graft organ
      rejection in renal transplant patients, were observed in seven (8.3%) patients.
      In multivariate analyses, cardiovascular disease (OR 17.1, 95% CI 2.17-403) and
      renal transplant (OR 13.0, 95% CI 1.63-281) were risk-factors for a potassium
      decrease of >20%. Age >65 years (OR 11.6, 95% CI 1.89-224) was a risk-factor for
      diarrhoea lasting >2 days. Immunosuppression (OR 5.7, 95% CI 1.78-20.1) was a
      risk-factor for a creatinine increase of >10%. Norovirus infections in patients
      with underlying conditions such as cardiovascular disease, renal transplant and
      immunosuppressive therapy may lead to severe consequences typified by decreased
      potassium levels, increased levels of C-reactive protein and creatine
      phosphokinase. In the elderly, norovirus infection may lead to an increased
      duration of diarrhoea. Therefore patients at risk should be hospitalised early
      and monitored frequently. Strict preventional measures should be implemented as
      early as possible to minimise the risk of nosocomial outbreaks.

PMID- 16460550
TI  - Epidemiology of candidaemia and antifungal susceptibility patterns in an Italian
      tertiary-care hospital.
AB  - The epidemiological and antifungal susceptibility data for 94 episodes of
      candidaemia in an Italian tertiary-care hospital between January 2000 and August
      2003 were evaluated by prospective laboratory-based surveillance. The incidence
      of fungaemia was 0.90 episodes/10 000 patient-days, and the most common species
      isolated were Candida albicans (40.4%), Candida parapsilosis (22.3%), Candida
      tropicalis (16.0%) and Candida glabrata (12.8%). Among 24 patients who received
      antifungal prophylaxis, non-albicans Candida spp. were more prevalent than C.
      albicans (p 0.012). The 30-day mortality rate was high (38.2%), particularly for
      haematological (71.4%) and solid-organ transplant patients (50.0%), and in
      individuals with C. tropicalis and C. glabrata bloodstream infections (60.0% and
      50.0%, respectively). In-vitro susceptibility tests demonstrated that 95% of the
      isolates were susceptible to amphotericin B (MIC < 2 mg/L), 98.1% to posaconazole
      (MIC < 1 mg/L), 95.8% to flucytosine (MIC < 32 mg/L) and fluconazole (MIC < 64
      mg/L), and 94.7% to itraconazole (MIC < 1 mg/L). Posaconazole was active (MIC 0.5
      mg/L) against all three isolates of Candida krusei, which had reduced
      susceptibility to both fluconazole and itraconazole. Overall, non-albicans
      Candida spp. accounted for 60% of the episodes of candidaemia, which could be
      related to the use of antifungal prophylaxis. Resistance is still uncommon in
      Candida spp. recovered from blood cultures. The in-vitro activity of posaconazole
      is encouraging, and this agent could play an important role in the management of
      invasive candidiasis, including episodes caused by inherently less susceptible
      species such as C. krusei.

PMID- 16460551
TI  - The point prevalence and associated factors of nasal methicillin-resistant
      Staphylococcus aureus colonisation in eight geriatric hospitals in Korea.
AB  - The prevalence and associated factors of nasal methicillin-resistant
      Staphylococcus aureus (MRSA) colonisation were investigated among patients in
      geriatric hospitals in Korea. S. aureus was isolated from 317 (50.2%) of 632
      patients. The nasal MRSA colonisation prevalence was 36.1%. In bivariate
      analysis, stay in an intensive care unit, decreased functional status, recent use
      of antibiotics, use of urinary catheters and the existence of skin breaks were
      associated with nasal MRSA colonisation (p < 0.05). Of these factors, only
      decreased functional status and recent use of systemic antibiotics were
      associated independently with nasal MRSA colonisation following logistic
      regression analysis.

PMID- 16460552
TI  - Identification and susceptibility testing of Staphylococcus aureus by direct
      inoculation from positive BACTEC blood culture bottles.
AB  - This study explored the possibility of combining direct inoculation of tube
      coagulase and DNase tests, and the VITEK2 system, from BACTEC blood culture
      bottles in order to achieve rapid identification and susceptibility testing of
      Staphylococcus aureus. All isolates were identified correctly as S. aureus or
      coagulase-negative staphylococci (CNS). Antimicrobial susceptibility testing with
      the VITEK2 system gave 99.6% correct category agreement, with 0.1% very major
      errors and 0.3% minor errors among S. aureus isolates, and 97.4% correct category
      agreement, with 0.9% very major errors and 1.7% minor errors among CNS isolates.
      The results suggested that direct identification and susceptibility testing is
      sufficiently accurate for immediate reporting.

PMID- 16460553
TI  - Antimicrobial susceptibility patterns of Haemophilus influenzae and Streptococcus
      pneumoniae isolates in a Beirut general university hospital between 2000 and
      2004.
AB  - Susceptibility patterns of Streptococcus pneumoniae and Haemophilus influenzae
      collected over a 5-year period in a Beirut general university hospital were
      studied. Only 40.6-50% of S. pneumoniae isolates were susceptible to penicillin
      G. Susceptibility to clindamycin and erythromycin decreased from 94.1% and 89.7%,
      respectively, in 2000 to 75% and 71.9%, respectively, in 2004. All isolates were
      susceptible to ceftriaxone, ciprofloxacin and vancomycin. For H. influenzae, no
      resistance was observed to amoxycillin-clavulanate, ceftriaxone, ciprofloxacin
      and rifampicin, with >92% of isolates showing susceptibility to cefuroxime,
      chloramphenicol, erythromycin and tetracycline. The proportion of beta-lactamase
      positive isolates varied between 22.7 and 30.8%.

PMID- 16460554
TI  - Patterns of delays in diagnosis amongst patients with smear-positive pulmonary
      tuberculosis at a teaching hospital in Turkey.
AB  - In total, 151 newly diagnosed patients with smear-positive pulmonary tuberculosis
      were studied. The mean time from the onset of symptoms to the first visit to a
      physician was 46.4 days; the mean referral delay was 28.9 days; the mean delay in
      diagnosis was 2.4 days; and the mean delay in treatment initiation was 0.8 days.
      There was a delay in consulting a physician by 49% of patients. A low index of
      suspicion for tuberculosis on the part of the physician and healthcare system and
      laboratory delays were the most common reasons for delays in diagnosis.

PMID- 16460555
TI  - Monitoring of vancomycin serum levels for the treatment of staphylococcal
      infections.
AB  - Vancomycin serum concentrations were determined for 1,737 patients treated with
      either 2 x 1 g of vancomycin or 4 x 500 mg daily (780 patients), according to
      current nomograms, or by continuous infusion (957 patients) with a loading dose
      (1 g) and a total of 2-6 g daily. Trough serum concentrations were determined
      after 36-48 h. Adequate serum levels for the treatment of a normal methicillin
      resistant Staphylococcus aureus (MRSA) and a glycopeptide-intermediate S. aureus
      (GISA) were observed in 81% and 20.9% of patients, respectively. The data support
      theoretical arguments that higher and more sustained serum levels of vancomycin,
      obtained by continuous infusion, may enhance clinical efficacy.

PMID- 16460556
TI  - Teicoplanin use and emergence of Staphylococcus haemolyticus: is there a link?

PMID- 16460557
TI  - Turkish isolates of Helicobacter pylori belong to the Middle Eastern genotypes.

PMID- 16460558
TI  - Impact of different strategies to control Plasmodium infection and anaemia on the
      island of Bioko (Equatorial Guinea).
AB  - BACKGROUND: On the island of Bioko (Equatorial Guinea), insecticide-treated nets
      (ITNs) have been the main tool used to control malaria over the last 13 years. In
      2004, started an indoor residual spraying (IRS) campaign to control malaria. The
      purpose of this study is to asses the impact of the two control strategies on the
      island of Bioko (Equatorial Guinea), with regards to Plasmodium infection and
      anaemia in the children under five years of age. METHODS: Two transversal
      studies, the first one prior to the start of the IRS campaign and the second one
      year later. Sampling was carried out by stratified clusters. Malaria infection
      was measured by means of thick and thin film, and the packed cell volume (PCV)
      percentage. Data related to ITN use and information regarding IRS were collected.
      The Pearson's chi-square and logistic regression statistical tests were used to
      calculate odds ratios (OR). RESULTS: In the first survey, 168 children were
      sampled and 433 children in the second one. The prevalence of infection was 40%
      in 2004, and significantly lower at 21.7% in 2005. PCV was 41% and 39%,
      respectively. 58% of the children surveyed in 2004 and 44.3% in 2005 had slept
      under an ITN. 78% of the dwellings studied in 2005 had been sprayed. In the 2005
      survey, sleeping without a mosquito net meant a risk of infection 3 times greater
      than sleeping protected with a net hanged correctly and with no holes (p < 0.05).
      CONCLUSION: IRS and ITNs have proven to be effective control strategies on the
      island of Bioko. The choice of one or other strategy is, above all, a question of
      operational feasibility and availability of local resources.

PMID- 16460560
TI  - PDB-UF: database of predicted enzymatic functions for unannotated protein
      structures from structural genomics.
AB  - BACKGROUND: The number of protein structures from structural genomics centers
      dramatically increases in the Protein Data Bank (PDB). Many of these structures
      are functionally unannotated because they have no sequence similarity to proteins
      of known function. However, it is possible to successfully infer function using
      only structural similarity. RESULTS: Here we present the PDB-UF database, a web
      accessible collection of predictions of enzymatic properties using structure
      function relationship. The assignments were conducted for three-dimensional
      protein structures of unknown function that come from structural genomics
      initiatives. We show that 4 hypothetical proteins (with PDB accession codes:
      1VH0, 1NS5, 1O6D, and 1TO0), for which standard BLAST tools such as PSI-BLAST or
      RPS-BLAST failed to assign any function, are probably methyltransferase enzymes.
      CONCLUSION: We suggest that the structure-based prediction of an EC number should
      be conducted having the different similarity score cutoff for different protein
      folds. Moreover, performing the annotation using two different algorithms can
      reduce the rate of false positive assignments. We believe, that the presented web
      based repository will help to decrease the number of protein structures that have
      functions marked as "unknown" in the PDB file. AVAILABILITY:
      http://paradox.harvard.edu/PDB-UF and http://bioinfo.pl/PDB-UF.

PMID- 16460559
TI  - Epigenetics and airways disease.
AB  - Epigenetics is the term used to describe heritable changes in gene expression
      that are not coded in the DNA sequence itself but by post-translational
      modifications in DNA and histone proteins. These modifications include histone
      acetylation, methylation, ubiquitination, sumoylation and phosphorylation.
      Epigenetic regulation is not only critical for generating diversity of cell types
      during mammalian development, but it is also important for maintaining the
      stability and integrity of the expression profiles of different cell types. Until
      recently, the study of human disease has focused on genetic mechanisms rather
      than on non-coding events. However, it is becoming increasingly clear that
      disruption of epigenetic processes can lead to several major pathologies,
      including cancer, syndromes involving chromosomal instabilities, and mental
      retardation. Furthermore, the expression and activity of enzymes that regulate
      these epigenetic modifications have been reported to be abnormal in the airways
      of patients with respiratory disease. The development of new diagnostic tools
      might reveal other diseases that are caused by epigenetic alterations. These
      changes, despite being heritable and stably maintained, are also potentially
      reversible and there is scope for the development of 'epigenetic therapies' for
      disease.

PMID- 16460561
TI  - Antimicrobial resistance of Escherichia coli isolates from broiler chickens and
      humans.
AB  - BACKGROUND: Antimicrobial usage is considered the most important factor promoting
      the emergence, selection and dissemination of antimicrobial-resistant
      microorganisms in both veterinary and human medicine. The aim of this study was
      to investigate the prevalence and genetic basis of tetracycline resistance in
      faecal Escherichia coli isolates from healthy broiler chickens and compare these
      data with isolates obtained from hospitalized patients in Jamaica. RESULTS:
      Eighty-two E. coli strains isolated from faecal samples of broiler chickens and
      urine and wound specimens of hospitalized patients were analyzed by agar disc
      diffusion to determine their susceptibility patterns to 11 antimicrobial agents.
      Tetracycline resistance determinants were investigated by plasmid profiling,
      transformations, and amplification of plasmid-borne resistance genes.
      Tetracycline resistance occurred at a frequency of 82.4% in avian isolates
      compared to 43.8% in human isolates. In addition, among avian isolates there was
      a trend towards higher resistance frequencies to kanamycin and nalidixic acid (p
      < 0.05), while a greater percentage of human isolates were resistant to
      chloramphenicol and gentamicin (p < 0.05). Multiple drug resistance was found in
      isolates from both sources and was usually associated with tetracycline
      resistance. Tetracycline-resistant isolates from both avian and human sources
      contained one or several plasmids, which were transmissible by transformation of
      chemically-competent E. coli. Tetracycline resistance was mediated by efflux
      genes tetB and/or tetD. CONCLUSION: The present study highlights the prevalence
      of multiple drug resistant E. coli among healthy broiler chickens in Jamaica,
      possibly associated with expression of tetracycline resistance. While there did
      not appear to be a common source for multiple drug resistance in the strains from
      avian or human origin, the genes encoding resistance are similar. These results
      suggest that genes are disseminated in the environment and warrant further
      investigation of the possibility for avian sources acting as reservoirs for
      tetracycline resistance.

PMID- 16460563
TI  - Expression of early transcription factors Oct-4, Sox-2 and Nanog by porcine
      umbilical cord (PUC) matrix cells.
AB  - BACKGROUND: Three transcription factors that are expressed at high levels in
      embryonic stem cells (ESCs) are Nanog, Oct-4 and Sox-2. These transcription
      factors regulate the expression of other genes during development and are found
      at high levels in the pluripotent cells of the inner cell mass. The
      downregulation of these three transcription factors correlates with the loss of
      pluripotency and self-renewal, and the beginning of subsequent differentiation
      steps. The roles of Nanog, Oct-4 and Sox-2 have not been fully elucidated. They
      are important in embryonic development and maintenance of pluripotency in ESCs.
      We studied the expression of these transcription factors in porcine umbilical
      cord (PUC) matrix cells. METHODS: Cells were isolated from Wharton's jelly of
      porcine umbilical cords (PUC) and histochemically assayed for the presence of
      alkaline phosphatase and the presence of Nanog, Oct-4 and Sox-2 mRNA and protein.
      PCR amplicons were sequenced and compared with known sequences. The synthesis of
      Oct-4 and Nanog protein was analyzed using immunocytochemistry. FACS analysis was
      utilized to evaluate Hoechst 33342 dye-stained cells. RESULTS: PUC isolates were
      maintained in culture and formed colonies that express alkaline phosphatase. FACS
      analysis revealed a side population of Hoechst dye-excluding cells, the Hoechst
      exclusion was verapamil sensitive. Quantitative and non-quantitative RT-PCR
      reactions revealed expression of Nanog, Oct-4 and Sox-2 in day 15 embryonic
      discs, PUC cell isolates and porcine fibroblasts. Immunocytochemical analysis
      detected Nanog immunoreactivity in PUC cell nuclei, and faint labeling in
      fibroblasts. Oct-4 immunoreactivity was detected in the nuclei of some PUC cells,
      but not in fibroblasts. CONCLUSION: Cells isolated from PUC express three
      transcription factors found in pluripotent stem cell markers both at the mRNA and
      protein level. The presence of these transcription factors, along with the other
      characteristics of PUC cells such as their colony-forming ability, Hoechst dye
      excluding side population and alkaline phosphatase expression, suggests that PUC
      cells have properties of primitive pluripotent stem cells. Furthermore, PUC cells
      are an easily and inexpensively obtained source of stem cells that are not
      hampered by the ethical or legal issues associated with ESCs. In addition, these
      cells can be cryogenically stored and expanded.

PMID- 16460562
TI  - Can inhaled fluticasone alone or in combination with salmeterol reduce systemic
      inflammation in chronic obstructive pulmonary disease? Study protocol for a
      randomized controlled trial [NCT00120978].
AB  - BACKGROUND: Systemic inflammation is associated with various complications in
      chronic obstructive pulmonary disease including weight loss, cachexia,
      osteoporosis, cancer and cardiovascular diseases. Inhaled corticosteroids
      attenuate airway inflammation, reduce exacerbations, and improve mortality in
      chronic obstructive pulmonary disease. Whether inhaled corticosteroids by
      themselves or in combination with a long-acting beta2-adrenoceptor agonist
      repress systemic inflammation in chronic obstructive pulmonary disease is
      unknown. The Advair Biomarkers in COPD (ABC) study will determine whether the
      effects of inhaled corticosteroids alone or in combination with a long-acting
      beta2-adrenoceptor agonist reduce systemic inflammation and improve health status
      in patients with chronic obstructive pulmonary disease. METHODS/DESIGN: After a 4
      week run-in phase during which patients with stable chronic obstructive pulmonary
      disease will receive inhaled fluticasone (500 micrograms twice daily), followed
      by a 4-week withdrawal phase during which all inhaled corticosteroids and long
      acting beta2-adrenoceptor agonists will be discontinued, patients will be
      randomized to receive fluticasone (500 micrograms twice daily),
      fluticasone/salmeterol combination (500/50 micrograms twice daily), or placebo
      for four weeks. The study will recruit 250 patients across 11 centers in western
      Canada. Patients must be 40 years of age or older with at least 10 pack-year
      smoking history and have chronic obstructive pulmonary disease defined as forced
      expiratory volume in one second to vital capacity ratio of 0.70 or less and
      forced expiratory volume in one second that is 80% of predicted or less. Patients
      will be excluded if they have any known chronic systemic infections, inflammatory
      conditions, history of previous solid organ transplantation, myocardial
      infarction, or cerebrovascular accident within the past 3 months prior to study
      enrollment. The primary end-point is serum C-reactive protein level. Secondary
      end-points include circulating inflammatory cytokines such as interleukin-6 and
      interleukin-8 as well as health-related quality of life and lung function.
      DISCUSSION: If inhaled corticosteroids by themselves or in combination with a
      long-acting beta2-adrenoceptor agonist could repress systemic inflammation, they
      might greatly improve clinical prognosis by reducing various complications in
      chronic obstructive pulmonary disease.

PMID- 16460564
TI  - Effects of CPAP on right ventricular myocardial performance index in obstructive
      sleep apnea patients without hypertension.
AB  - OBJECTIVES: Obstructive sleep apnoea (OSA) might cause right ventricular
      dysfunction and pulmonary hypertension. We aimed to determine the effects of
      nasal continuous positive airway pressure (CPAP) therapy on right ventricular
      myocardial performance index (MPI) in OSA patients without hypertension. METHODS:
      49 subjects without hypertension, diabetes mellitus, any cardiac and pulmonary
      disease had overnight polysomnography and echocardiography. In 18 moderate-severe
      OSA (apnea-hypopnea index > or = 15) patients, right ventricular free wall
      diameter (RVFWD) was measured by M-mode, and right ventricular MPI was calculated
      as (isovolumic contraction time+ isovolumic relaxation time) / pulmonary ejection
      time using Doppler at baseline and after 6 months CPAP therapy. RESULTS: Mean age
      was 46.5 +/- 4.9 year. Patients had high body mass index (BMI: 30.6 +/- 4,0
      kg/m2), but there was no change in either BMI or blood pressures after 6 months.
      Right ventricular end-diastolic and end-systolic diameters were in normal limits
      at baseline, and did not change after CPAP usage. Baseline RVFWD (7.1 +/- 2.1 mm)
      significantly decreased after CPAP therapy (6.2 +/- 1.7 mm, p < 0.001). 15 of
      patients (83%) had right ventricular diastolic dysfunction at baseline, and it
      was completely improved in 11 of them (73%) by CPAP usage. Right ventricular
      global dysfunction was shown in 11 patients (61%) with a high MPI (62.2 +/- 9.3%)
      at baseline; and MPI was significantly decreased after CPAP therapy (47.3 +/-
      8.4%, p < 0.0001), and it was completely corrected in 4 of them (36%).
      CONCLUSION: CPAP therapy significantly decreases RVFWD and improves right
      ventricular diastolic and global functions (MPI) in OSA patients without
      hypertension.

PMID- 16460565
TI  - Release of Ca2+ and Mg2+ from yeast mitochondria is stimulated by increased ionic
      strength.
AB  - BACKGROUND: Divalent cations are required for many essential functions of
      mitochondrial metabolism. Yet the transporters that mediate the flux of these
      molecules into and out of the mitochondrion remain largely unknown. Previous
      studies in yeast have led to the molecular identification of a component of the
      major mitochondrial electrophoretic Mg2+ uptake system in this organism as well
      as a functional mammalian homolog. Other yeast mitochondrial studies have led to
      the characterization of an equilibrative fatty acid-stimulated Ca2+ transport
      activity. To gain a deeper understanding of the regulation of mitochondrial
      divalent cation levels we further characterized the efflux of Ca2+ and Mg2+ from
      yeast mitochondria. RESULTS: When isolated mitochondria from the yeast
      Saccharomyces cerevisiae were suspended in a salt-based suspension medium, Ca2+
      and Mg2+ were released from the matrix space. Release did not spontaneously occur
      in a non-ionic mannitol media. When energized mitochondria were suspended in a
      mannitol medium in the presence of Ca2+ they were able to accumulate Ca2+ by the
      addition of the electrogenic Ca2+ ionophore ETH-129. However, in a KCl or choline
      Cl medium under the same conditions, they were unable to retain the Ca2+ that was
      taken up due to the activation of the Ca2+ efflux pathway, although a substantial
      membrane potential driving Ca2+ uptake was maintained. This Ca2+ efflux was
      independent of fatty acids, which have previously been shown to activate Ca2+
      transport. Endogenous mitochondrial Mg2+ was also released when mitochondria were
      suspended in an ionic medium, but was retained in mitochondria upon fatty acid
      addition. When suspended in a mannitol medium, metal chelators released
      mitochondrial Mg2+, supporting the existence of an external divalent cation
      binding site regulating release. Matrix space Mg2+ was also slowly released from
      mitochondria by the addition of Ca2+, respiratory substrates, increasing pH, or
      the nucleotides ATP, ADP, GTP, and ATP-gamma-S. CONCLUSION: In isolated yeast
      mitochondria Ca2+ and Mg2+ release was activated by increased ionic strength.
      Free nucleotides, metal ion chelators, and increased pH also stimulated release.
      In yeast cells this release is likely an important mechanism in the regulation of
      mitochondrial matrix space divalent cation concentrations.

PMID- 16460566
TI  - An integrated psychological strategy for advanced colorectal cancer patients.
AB  - BACKGROUND: There is evidence regarding the usefulness of psychosocial
      intervention to improve health related quality of life (HRQOL) in adult cancer
      patients. The aim of this report is to describe an integrated approach and to
      evaluate its feasibility in routine clinical practice in 98 advanced colorectal
      cancer (ACC) patients during chronomodulated chemotherapy. METHODS: A prospective
      non-randomised design was developed and applied in a cancer out-patient setting.
      The intervention consisted of an integrated approach, whereby the psycho
      oncologist had an active role in the health care team with the physician and
      routinely included psychological understanding in the medical treatment program.
      The psychological evaluation assessed: a) adaptation, awareness,
      psychopathological disorders through a psychodynamic interview; b) anxiety and
      depression using the HAD scale; c) subjective perception of care quality through
      a structured interview and d) HRQOL evaluation assessment with the EORTC QLQ C30.
      Outcomes data were collected before and after 18 weeks of chemotherapy. RESULTS:
      After 18 weeks of chemotherapy a significant improvement of adaptation and
      awareness was observed. The HADs results showed a significant decrease in anxiety
      when compared to pre-treatment. The structured interview showed a significant
      increase of patients who positively experienced the impact of medical treatment
      on HRQOL, anxiety, depression, interpersonal relationships, free-time and who
      positively experienced the care quality. Indeed, a majority of patients
      positively experienced the team relationship modality during the whole treatment.
      All scales on the EORTC questionnaire remained unchanged during the entire
      treatment. CONCLUSION: Our results suggest that it is feasible to carry out an
      integrated approach during chemotherapy. These results seem to support the
      integrated approach as a tool in aiding advanced colorectal cancer patients'
      ability to cope with their diagnosis and treatment although an appropriately
      designed study is required to confirm this.

PMID- 16460567
TI  - Are mild head injuries as mild as we think? Neurobehavioral concomitants of
      chronic post-concussion syndrome.
AB  - BACKGROUND: Mild traumatic brain injury (MTBI) can sometimes lead to persistent
      postconcussion symptoms. One well accepted hypothesis claims that chronic PCS has
      a neural origin, and is related to neurobehavioral deficits. But the evidence is
      not conclusive. In the attempt to characterise chronic MTBI consequences, the
      present experiment used a group comparison design, which contrasted persons (a)
      with MTBI and PCS, (b) MTBI without PCS, and (c) matched controls. We predicted
      that participants who have experienced MTBI but show no signs of PCS would
      perform similar to controls. At the same time, a subgroup of MTBI participants
      would show PCS symptoms and only these volunteers would have poorer cognitive
      performance. Thereby, the performance deficits should be most noticeable in
      participants with highest PCS severity. METHOD: 38 patients with a single MTBI
      that had occurred at least 12 month prior to testing, and 38 matched controls,
      participated in the experiment. A combination of questionnaires and
      neuropsychological test batteries were used to assess the extent of PCS and
      related deficits in neurobehavioral performance. RESULTS: 11 out of 38 MTBI
      participants (29%) were found to suffer from PCS. This subgroup of MTBI patients
      performed poorly on neuropsychological test batteries. Thereby, a correlation was
      found between PCS symptom severity and test performance suggesting that
      participants with more pronounced PCS symptoms performed worse in cognitive
      tasks. In contrast, MTBI patients with no PCS showed performed similar to matched
      control. We further found that loss of consciousness, a key criterion for PCS
      diagnosis, was not predictive of sustained PCS. CONCLUSION: The results support
      the idea that MTBI can have sustained consequences, and that the subjectively
      experienced symptoms and difficulties in everyday situations are related to
      objectively measurable parameters in neurocognitive function.

PMID- 16460569
TI  - Cytologic findings of peripheral T-cell lymphoma (PTCL) with high epitheloid cell
      content (Lennert's lymphoma) in imprint smear. A case report.
AB  - BACKGROUND: Lymphoepitheloid lymphoma is a T-cell lymphoma with peculiar
      histologic picture with massive proliferation of epitheloid cell clusters
      intermingled with many, mostly small-sized lymphoid cells. The cytomorphologic
      features in imprint of a case of lymphoepitheloid T-cell lymphoma is described
      together with diagnostic pitfalls. CASE REPORT: A 74 years old man presented with
      weight loss, anemia and fever. Physical examination showed bilateral cervical
      lymphadenopathy with hepatosplenomegaly. With the clinical impression of
      hypersplenic syndrome vs lymphoma, excisional biopsy of a lymph node was
      performed and both imprints and histologic sections made. Cytologic findings
      showed uniform isolated small lympocytes with closely intermingled scattered and
      aggregates of epitheloid cells. Histologic sections were diagnosed as
      lymphoepitheloid lymphoma (Lennert's lymphoma). CONCLUSION: Cytologic findings of
      this variant of lymphoma is distinctive enough for a correct initial suggestive
      diagnosis. However the presence of high content of epitheloid cell clusters can
      cause cytologic misinterpretation with other benign and malignant conditions.

PMID- 16460568
TI  - Increasing illness severity in very low birth weight infants over a 9-year
      period.
AB  - BACKGROUND: Recent reports have documented a leveling-off of survival rates in
      preterm infants through the 1990's. The objective of this study was to determine
      temporal changes in illness severity in very low birth weight (VLBW) infants in
      relationship to the outcomes of death and/or severe IVH. METHODS: Cohort study of
      1414 VLBW infants cared for in a single level III neonatal intensive care unit in
      Delaware from 1993-2002. Infants were divided into consecutive 3-year cohorts.
      Illness severity was measured by two objective methods: the Score for Neonatal
      Acute Physiology (SNAP), based on data from the 1st day of life, and total
      thyroxine (T4), measured on the 5th day of life. Death before hospital discharge
      and severe intraventricular hemorrhage (IVH) were investigated in the study
      sample in relation to illness severity. The fetal death rate was also
      investigated. Statistical analyses included both univariate and multivariate
      analysis. RESULTS: Illness severity, as measured by SNAP and T4, increased
      steadily over the 9-year study period with an associated increase in severe IVH
      and the combined outcome of death and/or severe IVH. During the final 3 years of
      the study, the observed increase in illness severity accounted for 86% (95% CI 57
      116%) of the variability in the increase in death and/or severe IVH. The fetal
      death rate dropped from 7.8/1000 (1993-1996) to 5.3/1000 (1999-2002, p = .01)
      over the course of the study. CONCLUSION: These data demonstrate a progressive
      increase in illness in VLBW infants over time, associated with an increase in
      death and/or severe IVH. We speculate that the observed decrease in fetal death,
      and the increase in neonatal illness, mortality and/or severe IVH over time
      represent a shift of severely compromised patients that now survive the fetal
      time period and are presented for care in the neonatal unit.

PMID- 16460570
TI  - Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci
      in the liver and colon of rats.
AB  - Chlorophyllin (CHL) is a promising chemopreventive agent believed to block cancer
      primarily by inhibiting carcinogen uptake through the formation of molecular
      complexes with the carcinogens. However, recent studies suggest that CHL may have
      additional biological effects particularly when given after the period of
      carcinogen treatment. This study examines the post-initiation effects of CHL
      towards aflatoxin B1 (AFB1)-induced preneoplastic foci of the liver and colon.
      The single concentration of CHL tested in this study (0.1% in the drinking water)
      had no significant effects on AFB1-induced foci of the liver and colons of rats.

PMID- 16460571
TI  - An inquiry into good hospital governance: a New Zealand-Czech comparison.
AB  - BACKGROUND: This paper contributes to research in health systems literature by
      examining the role of health boards in hospital governance. Health care ranks
      among the largest public sectors in OECD countries. Efficient governance of
      hospitals requires the responsible and effective use of funds, professional
      management and competent governing structures. In this study hospital governance
      practice in two health care systems - Czech Republic and New Zealand - is
      compared and contrasted. These countries were chosen as both, even though they
      are geographically distant, have a universal right to 'free' health care provided
      by the state and each has experienced periods of political change and ensuing
      economic restructuring. Ongoing change has provided the impetus for policy reform
      in their public hospital governance systems. METHODS: Two comparative case
      studies are presented. They define key similarities and differences between the
      two countries' health care systems. Each public hospital governance system is
      critically analysed and discussed in light of D W Taylor's nine principles of
      'good governance'. RESULTS: While some similarities were found to exist, the key
      difference between the two countries is that while many forms of 'ad hoc'
      hospital governance exist in Czech hospitals, public hospitals in New Zealand are
      governed in a 'collegiate' way by elected District Health Boards. These findings
      are discussed in relation to each of the suggested nine principles utilized by
      Taylor. CONCLUSION: This comparative case analysis demonstrates that although the
      New Zealand and Czech Republic health systems appear to show a large degree of
      convergence, their approaches to public hospital governance differ on several
      counts. Some of the principles of 'good governance' existed in the Czech
      hospitals and many were practiced in New Zealand. It would appear that the
      governance styles have evolved from particular historical circumstances to meet
      each country's specific requirements. Whether or not current practice could be
      improved by paying closer attention to theoretical models of 'good governance' is
      debatable.

PMID- 16460572
TI  - Screening mammography in women aged 40-49: is it time to change?
AB  - There is little doubt that significant benefits can accrue from carrying out
      screening mammography of women aged 40-49 in the setting of a highly quality
      assured service delivery. This will best be achieved using digital mammography to
      maximise detection rates and trained and high volume reading expert radiologists
      to apply economic cushions of optimising specificity as well as sensitivity in
      addition to utilising modern and accurate assessment and tissue sampling
      techniques that have evolved.

PMID- 16460573
TI  - Electrical impedance tomography imaging using a priori ultrasound data.
AB  - BACKGROUND: Different imaging systems (e.g. electrical, magnetic, and ultrasound)
      rely on a wide variety of physical properties, and the datasets obtained from
      such systems provide only partial information about the unknown true state. One
      approach is to choose complementary imaging systems, and to combine the
      information to achieve a better representation. METHODS: This paper discusses the
      combination of ultrasound and electrical impedance tomography (EIT) information.
      Ultrasound reflection signals are good at locating sharp acoustic density changes
      associated with the boundaries of objects. Some boundaries, however, may be
      indeterminable due to masking from intermediate boundaries or because they are
      outside the ultrasound beam. Conversely, the EIT data contains relatively low
      quality information, but it includes the whole region enclosed by the electrodes.
      RESULTS: Results are shown from a narrowband level-set method applied to 2D and
      3D EIT incorporating limited angle ultrasound time of flight data. CONCLUSION:
      The EIT reconstruction is shown to be faster and more accurate using the
      additional edge information from both one and four transducer ultrasound systems.

PMID- 16460574
TI  - Preliminary report of a gas conditioner to improve operational reliability of
      cryotherapy in developing countries.
AB  - BACKGROUND: Cryotherapy is a safe, affordable, and effective method of treatment
      for cervical intraepithelial neoplasia. In some low-resource settings,
      environmental conditions or qualities of the refrigerant gas can lead to blockage
      of cryotherapy equipment, terminating treatment. A prototype of a gas conditioner
      to prevent operational failure was designed, built, and field tested. METHODS:
      The prototype conditioner device consists of an expansion chamber that filters
      and dries the refrigerant gas. Users in Peru and Kenya reported on their
      experience with the prototype conditioner. In Ghana, simulated cryotherapy
      procedures were used to test the effects of the prototype conditioner, as well as
      the commonly used "cough technique." RESULTS: Anecdotal reports from field use of
      the device were favorable. During simulated cryotherapy, the prevalence of
      blockage during freezing were 0% (0/25) with the device alone, 23.3% (7/30) with
      the cough technique alone, 5.9% (1/17) with both, and 55.2% (16/29) with neither
      (Pearson's Chi square = 26.6, df = 3, p < 0.001 (comparison amongst all groups)).
      CONCLUSION: This prototype design of a cryotherapy gas conditioner is a potential
      solution for low-resource settings that are experiencing cryotherapy device
      malfunction.

PMID- 16460576
TI  - Journal of Ethnobiology and Ethnomedicine - achievements and perspectives.
AB  - Last summer we officially launched the Journal of Ethnobiology and Ethnomedicine,
      published by BioMedCentral, with the aim of establishing a serious, peer
      reviewed, open-access online journal that focuses on the multidisciplinary,
      interdisciplinary, and transdisciplinary fields of ethnobiology and
      ethnomedicine, drawing on approaches and methods from both the social and
      biological sciences. The strong start vindicates the widely held belief that the
      journal responds to a real need within the research community. The success of the
      journal has been most gratifying. The steady influx of submissions of high
      scientific standards illustrates the strong demand for a dynamic, proactive, and
      open-minded scientific journal in these research areas. Our aim has been to
      dedicate JEE to the "scientific communities" worldwide, particularly those in the
      developing countries.

PMID- 16460575
TI  - Patterns of evolution of host proteins involved in retroviral pathogenesis.
AB  - BACKGROUND: Evolutionary analysis may serve as a useful approach to identify and
      characterize host defense and viral proteins involved in genetic conflicts. We
      analyzed patterns of coding sequence evolution of genes with known (TRIM5alpha
      and APOBEC3G) or suspected (TRIM19/PML) roles in virus restriction, or in viral
      pathogenesis (PPIA, encoding Cyclophilin A), in the same set of human and non
      human primate species. RESULTS AND CONCLUSION: This analysis revealed previously
      unidentified clusters of positively selected sites in APOBEC3G and TRIM5alpha
      that may delineate new virus-interaction domains. In contrast, our evolutionary
      analyses suggest that PPIA is not under diversifying selection in primates,
      consistent with the interaction of Cyclophilin A being limited to the HIV
      1M/SIVcpz lineage. The strong sequence conservation of the TRIM19/PML sequences
      among primates suggests that this gene does not play a role in antiretroviral
      defense.

PMID- 16460577
TI  - Use of mask continuous positive airway pressure in a preterm infant presenting
      with bilateral cleft lip and palate.
AB  - This report highlights innovative ways of overcoming difficulties in delivering
      effective continuous positive airway pressure in an extremely preterm baby with
      bilateral cleft lip and cleft palate.

PMID- 16460578
TI  - The bullet that hit a nerve: the history of Lucja Frey and her syndrome.
AB  - Duphenix first described gustatory sweating in 1757. The underlying pathogenesis
      was not appreciated until 1923, when Lucja Frey, a Polish neurologist, observed
      the phenomenon in a Polish soldier with an infected bullet wound in the parotid
      gland and suggested that the auriculo-temporal nerve played a role. Lucja Frey
      was born in Lwow, Poland, in 1889 and began her medical studies in Lwow before
      moving to Warsaw to work as a neurologist. She amassed a total of 43 publications
      on various neurological topics over her career. Unfortunately, during the Second
      World War she was enlisted into the Lwow ghetto, where she worked until her death
      in 1943. We present the history of Frey's syndrome, particularly the life of
      Lucja Frey and the syndrome she described.

PMID- 16460579
TI  - Septate fungal invasion in masked mastoiditis: a diagnostic dilemma.
AB  - Invasive fungal mastoiditis is a rare entity, seen almost entirely in
      immunocompromized patients. It has been reported primarily in patients with
      leukaemia and more recently with acquired immunodeficiency syndrome. A literature
      search revealed only a few reports in diabetic patients, in whom the invasive
      fungus was identified as mucormycosis in all cases. We report the first case in
      the English literature of invasive septate fungal mastoiditis in a diabetic
      patient with intact tympanic membranes.

PMID- 16460580
TI  - Using experimental manipulation to assess the roles of leaf litter in the
      functioning of forest ecosystems.
AB  - The widespread use of forest litter as animal bedding in central Europe for many
      centuries gave rise to the first litter manipulation studies, and their results
      demonstrated that litter and its decomposition are a vital part of ecosystem
      function. Litter plays two major roles in forest ecosystems: firstly, litterfall
      is an inherent part of nutrient and carbon cycling, and secondly, litter forms a
      protective layer on the soil surface that also regulates microclimatic
      conditions. By reviewing 152 years of litter manipulation experiments, I show
      that the effects of manipulating litter stem from changes in one, or both, of
      these two functions, and interactions between the variables influenced by the
      accumulation of litter can result in feedback mechanisms that may intensify
      treatment effects or mask responses, making the interpretation of results
      difficult.Long-term litter removal increased soil bulk density, overland flow,
      erosion, and temperature fluctuations and upset the soil water balance, causing
      lower soil water content during dry periods. Soil pH increased or decreased in
      response to manipulation treatments depending on forest type and initial soil pH,
      but it is unclear why there was no uniform response. Long-term litter harvesting
      severely depleted the forests of nutrients. Decreases in the concentrations of
      available P, Ca, Mg, and K in the soil occurred after only three to five years.
      The decline in soil N occurred over longer periods of time, and the relative loss
      was greater in soils with high initial nitrogen concentration. Tree growth
      declined with long-term litter removal, probably due to lower nutrient
      availability. Litter manipulation also added or removed large amounts of carbon
      thereby affecting microbial communities and altering soil respiration rates.
      Litter manipulation experiments have shown that litter cover acts as a physical
      barrier to the shoot emergence of small-seeded species; further, the microclimate
      maintained by the litter layer may be favourable to herbivores and pathogens and
      is important in determining later seedling survival and performance. Litter
      manipulation altered the competitive outcomes between tree seedlings and forbs,
      thereby influencing species composition and diversity; changes in the species
      composition of understorey vegetation following treatments occurred fairly
      rapidly. By decreasing substrate availability and altering the microclimate,
      litter removal changed fungal species composition and diversity and led to a
      decline in populations of soil fauna. However, litter addition did not provoke a
      corresponding increase in the abundance or diversity of fungi or soil fauna.Large
      scale long-term studies are still needed in order to investigate the interactions
      between the many variables affected by litter, especially in tropical and boreal
      forests, which have received little attention. Litter manipulation treatments
      present an opportunity to assess the effects of increasing primary production in
      forest ecosystems; specific research aims include assessing the effects of
      changes in litter inputs on the carbon and nutrient cycles, decomposition
      processes, and the turnover of organic matter.

PMID- 16460581
TI  - Modulation of aggressive behaviour by fighting experience: mechanisms and contest
      outcomes.
AB  - Experience in aggressive contests often affects behaviour during, and the outcome
      of, later contests. This review discusses evidence for, variations in, and
      consequences of such effects. Generally, prior winning experiences increase, and
      prior losing experiences decrease, the probability of winning in later contests,
      reflecting modifications of expected fighting ability. We examine differences in
      the methodologies used to study experience effects, and the relative importance
      and persistence of winning and losing experiences within and across taxa. We
      review the voluminous, but somewhat disconnected, literature on the
      neuroendocrine mechanisms that mediate experience effects. Most studies focus on
      only one of a number of possible mechanisms without providing a comprehensive
      view of how these mechanisms are integrated into overt behaviour. More carefully
      controlled work on the mechanisms underlying experience effects is needed before
      firm conclusions can be drawn. Behavioural changes during contests that relate to
      prior experience fall into two general categories. Losing experiences decrease
      willingness to engage in a contest while winning experiences increase willingness
      to escalate a contest. As expected from the sequential assessment model of
      contest behaviour, experiences become less important to outcomes of contests that
      escalate to physical fighting.A limited number of studies indicate that
      integration of multiple experiences can influence current contest behaviour.
      Details of multiple experience integration for any species are virtually unknown.
      We propose a simple additive model for this integration of multiple experiences
      into an individual's expected fighting ability. The model accounts for different
      magnitudes of experience effects and the possible decline in experience effects
      over time. Predicting contest outcomes based on prior experiences requires an
      algorithm that translates experience differences into contest outcomes. We
      propose two general types of model, one based solely on individual differences in
      integrated multiple experiences and the other based on the probability contests
      reach the escalated phase. The difference models include four algorithms
      reflecting possible decision rules that convert the perceived fighting abilities
      of two rivals into their probabilities of winning. The second type of algorithm
      focuses on how experience influences the probability that a subsequent contest
      will escalate and the fact that escalated contests may not be influenced by prior
      experience. Neither type of algorithm has been systematically
      investigated.Finally, we review models for the formation of dominance hierarchies
      that assume that prior experience influences contest outcome. Numerous models
      have reached varied conclusions depending on which factors examined in this
      review are included. We know relatively little about the importance of and
      variation in experience effects in nature and how they influence the dynamics of
      aggressive interactions in social groups and random assemblages of individuals.
      Researchers should be very active in this area in the next decade. The role of
      experience must be integrated with other influences on contest outcome, such as
      prior residency, to arrive at a more complete picture of variations in contest
      outcomes. We expect that this integrated view will be important in understanding
      other types of interactions between individuals, such as mating and predator-prey
      interactions, that also are affected significantly by prior experiences.

PMID- 16460584
TI  - Experimental stroke: ischaemic lesion volume and oedema formation differ among
      rat strains (a comparison between Wistar and Sprague-Dawley rats using MRI).
AB  - Investigating focal cerebral ischaemia requires animal models that are relevant
      to human stroke. This study was designed to evaluate the influence of early
      reperfusion and choice of rat strains on infarct volume and oedema formation.
      Thirty-six Wistar and Sprague-Dawley rats were subjected to temporary middle
      cerebral artery occlusion (MCAO) for 90 min (groups I and II) or to permanent
      MCAO (groups III and IV) using the suture technique. Ischaemic lesion volume and
      oedema formation were quantified 24 h after MCAO using 7T-magnetic resonance
      imaging (MRI). Impact of rat strains: Reperfusion led to significant larger
      ischaemic lesion volumes in Wistar rats as compared to Sprague-Dawley rats
      (P<0.0005). Oedema formation was similar in both rat strains. Permanent MCAO led
      to significantly larger ischaemic lesion volumes in Sprague-Dawley rats (P<0.05).
      Oedema formation, however, was significantly more accentuated in Wistar rats
      (P<0.005). Impact of reperfusion: Reperfusion did not cause any changes in
      ischaemic lesion volume in Wistar rats. Oedema formation, however, was
      significantly reduced (P<0.0005). In Sprague-Dawley rats, reperfusion caused a
      significant reduction of ischaemic lesion volume (P<0.00005), but did not modify
      oedema formation. These findings emphasize the critical importance of rat strain
      differences in experimental stroke research.

PMID- 16460585
TI  - Cardiorespiratory and minimum alveolar concentration sparing effects of a
      continuous intravenous infusion of dexmedetomidine in halothane or isoflurane
      anaesthetized rats.
AB  - Dexmedetomidine (DEX) is a highly selective alpha(2)-adrenoceptor agonist in both
      the central and peripheral nervous systems. Its cardiorespiratory effects have
      been described; however, these effects have not been reported when it is used in
      combination with volatile anaesthetics in rats. The cardiovascular and
      respiratory actions of a continuous intravenous infusion of 0.25 microg/kg/min of
      DEX administered to rats anaesthetized at 1 minimum alveolar concentration (MAC)
      of either halothane (HAL) or isoflurane (ISO) were studied. Twenty-eight rats
      were grouped into four treatment groups: HAL alone, ISO alone, DEX + HAL and DEX
      + ISO. The MAC(HAL) or MAC(ISO) was determined in each rat from alveolar gas
      samples at the time of tail clamping. Control MAC values, expressed as mean +/-
      standard deviation, were 1.31 +/- 0.1% for HAL and 1.46 +/- 0.05% for ISO. DEX
      reduced HAL MAC from 1.31 +/- 0.1% to 0.36 +/- 0.22% (72 +/- 17% MAC reduction)
      and ISO MAC from 1.46 +/- 0.05% to 0.83 +/- 0.2% (43 +/- 14% MAC reduction).
      Heart rate (HR) was decreased in both DEX groups at 1 MAC, with no differences
      between HAL and ISO. The mean arterial pressure was significantly depressed in
      the DEX + ISO group compared with the ISO only group. This difference in mean
      arterial blood pressure (MABP) was not seen between the DEX + HAL and HAL only
      groups. Respiratory depression was minor at 1 MAC with both inhalant
      anaesthetics. DEX reduced the MAC of HAL to a degree greater than it decreased
      the MAC of ISO. The effects of DEX on HR and ventilation were similar in rats
      anaesthetized with HAL or ISO at 1 MAC; however, hypotension was more pronounced
      when DEX was combined with ISO at 1 MAC.

PMID- 16460586
TI  - Effects of epidural morphine and transdermal fentanyl analgesia on physiology and
      behaviour after abdominal surgery in pigs.
AB  - The objective of this work was to evaluate the physiological and behavioural
      effects of opioid analgesic treatment in pigs subjected to abdominal surgery. Ten
      Swedish Landrace x Yorkshire pigs (20 +/- 4 kg b.w.) were submitted for
      intestinal cannulation. The pigs were allocated into two groups during one
      preoperative, one surgical and two postoperative days. All pigs were
      anaesthetized with medetomidine, tiletamine and zolazepam. One group was treated
      with epidural morphine (0.1 mg/kg) preoperatively, and transdermal fentanyl
      patches (50 microg/kg/h) were applied behind the ear immediately after surgery.
      The other group received epidural saline (equivalent volume) and placebo patches.
      All pigs were regularly weighed and clinically examined and repeated blood
      samples were analysed for serum concentrations of cortisol, beta-endorphin and
      fentanyl. Pre- and postoperative behaviours were evaluated by a swine specialist
      blinded to the treatment, three times a day, and were also videotape recorded for
      a total of 84 h per pig. No differences in behaviour were noted by the observer.
      During the first postoperative 12 h, treated pigs did not differ in activity
      compared with preoperative recordings, while untreated pigs were found to be less
      active. The treated group started to show interest in eating immediately after
      anaesthesia recovery, whereas the placebo group did not. During the 12-60 h
      postoperative period, the treated group had lower activity levels compared with
      the preoperative levels, which were similar to those in the placebo group.
      Treated pigs gained 0.5 +/- 0.2 kg during the subsequent two postoperative days,
      whereas the untreated pigs lost weight throughout the experiment. Cortisol
      concentration differed immediately after the surgery: Group P had 325 +/- 120
      nmol/L and Group M 159 +/- 49 nmol/L. beta-endorphin concentration did not differ
      between groups. The highest serum fentanyl concentration (0.37 +/- 0.3 ng/mL) was
      measured 24 h postoperatively. Preoperative epidural morphine in combination with
      postoperative transdermal fentanyl resulted in earlier return to normal activity
      levels and an immediate weight gain after surgery.

PMID- 16460587
TI  - Successful protocol of anaesthesia for measuring transepithelial nasal potential
      difference in spontaneously breathing mice.
AB  - Numerous difficulties arise during in vivo measurements of transepithelial nasal
      potential difference (PD) in mice, such as inadequate duration and depth of
      anaesthesia, bronchoaspiration of solutions perfused in the nose, and respiratory
      and/or cardiovascular depression. Anaesthesia was induced in adult C57 mice with
      intraperitoneal injection of a combination of fentanyl, droperidol and
      medetomidine, each of these at either a small dose (0.20, 10 and 0.33 mg/kg,
      respectively) or at a large dose (0.40, 20 and 0.40 mg/kg, respectively),
      combined with a fixed dose of 0.375 microg clonidine. In order to establish a
      pharmacokinetic-pharmacodynamic relationship, blood concentrations of the first
      three drugs were measured in 24 animals by liquid-chromatography tandem mass
      spectrometry. At the end of the experiment, naloxone, a competitive morphinic
      antagonist, and atipamezole, an alpha-2 adrenergic antagonist, were administered.
      Bronchoaspiration was prevented by tilting the animal head downwards and by
      absorbing the excess fluid from the opposite nostril and from the oral cavity.
      Optimal assessment of anaesthesia associated with regular respiration, loss of
      blink, pupillary and pedal withdrawal reflexes was obtained with doses of
      fentanyl, droperidol and medetomidine corresponding to 0.20, 20 and 0.40 mg/kg,
      respectively. Blood concentrations of fentanyl around 17 ng/mL induced loss of
      respiratory efforts and were followed by death during the experiment. Integrity
      of ion transport was demonstrated under continuous perfusion by successive
      depolarization after amiloride and repolarization after chloride-free solution.
      The combination investigated in this study lead to adequate surgical anaesthesia
      (stage III, plane 2) for prolonged nasal PD measurements in spontaneously
      breathing mice.

PMID- 16460588
TI  - Motor and sensory nerve conduction velocities in Yucatan minipigs.
AB  - Motor and/or sensory conduction velocities are used to assess peripheral nervous
      system disorders. Although the miniature pig represents a model of choice for
      long-term pharmacological experimentation, no study has so far been reported on
      this model in relation to the measurement of nerve conduction velocities. We
      developed the present technique and applied it to 34 3-18-month-old Yucatan
      minipigs. Motor and sensory conduction velocities were measured using the
      anterior tibial nerve and the internal plantar nerve, a branch of the posterior
      tibial nerve, respectively. The nerve conduction velocity data of motor (MNCV)
      and sensory (SNCV) nerves, together with the amplitude of the sensory nerve
      signal, were logarithmically dependent on the age of the tested animals
      (r(2)=0.92, 0.81 and 0.76, respectively). The mean values of MNCV and SNCV were
      70.9 +/- 1.1 and 67.9 +/- 0.2 m/s, respectively, at the age of 16 months for
      these miniature pigs. In order to validate this model, we compared it with other
      known models when the velocities reached a plateau at the end of the study. These
      values were found to be higher than those in humans or rats, but are comparable
      to those of the baboon, one of the best large animal models for human
      pathologies. Because the physiology and metabolism of the minipig resemble those
      of humans, and due to its long lifetime, this animal represents a good model for
      studying the development of neuropathology.

PMID- 16460589
TI  - Fluid collection within the synovial sheath of the tendon of the flexor hallus
      longus muscle in the tarsal joint of rats: an anatomic variant detectable with
      magnetic resonance imaging.
AB  - Magnetic resonance (MR) images of the right tarsal joint of 22 normal male
      Han:Wistar rats were acquired using a 4.7 T magnet. An intermediate-high signal
      area associated with the tendon of the flexor hallus longus muscle was noticed in
      three rats on T2-weighted images. These areas appeared as an intermediate-high
      signal on lightly T2-weighted images, but appeared as an iso-signal to muscle
      structure on proton density weighted images. Histology preparations showed that
      such areas were caused by a sizable fluid collection within the synovial sheath
      of the tendon of the flexor hallus longus muscle, with all other joint structures
      appearing normal. This anatomic variant could be potentially regarded as a lesion
      on T2-weighted MR images, such as inflamed tissue with oedema, especially when
      the spatial resolution and/or signal-to-noise ratio are not optimal.

PMID- 16460590
TI  - Detection of rat parvovirus type 1 and rat minute virus type 1 by polymerase
      chain reaction.
AB  - Two newly recognized parvovirus species, rat parvovirus 1 (RPV-1) and rat minute
      virus 1 (RMV-1), were recently identified in naturally infected rats. In this
      study, two polymerase chain reaction (PCR) assays were developed to specifically
      detect RPV-1 and RMV-1. The RPV-1 PCR assay amplified the expected 487-bp
      deoxyribonucleic acid (DNA) fragment only in the presence of RPV-1 DNA; the RMV-1
      PCR assay amplified the expected 843-bp product only from RMV-1 DNA, not from
      other rodent parvoviruses. The RPV-1 and the RMV-1 PCR assays detected
      approximately 18 and 70 copies of DNA template, respectively. These two PCR
      assays were shown to be sensitive, specific and rapid methods for detecting RPV-1
      and RMV-1 infections in rats. These assays may also be valuable for evaluation of
      biological specimens for parvovirus contamination.

PMID- 16460591
TI  - Helicobacter typhlonius was detected in the sex organs of three mouse strains but
      did not transmit vertically.
AB  - Helicobacter typhlonius, one of the most recently identified members of this
      rapidly expanding genus of bacteria, was detected by polymerase chain reaction
      (PCR) in an animal facility and studied for tissue distribution in sentinel mice
      (Helicobacter-free, barrier maintained). Immunodeficient athymic nude-nu (nu/nu),
      Helicobacter-sensitive C3H/HeJ and Helicobacter-resistant C57BL/6J mouse strains
      were used to study whether Helicobacter species could spread to the sex organs
      and be transmitted vertically. Sentinel mice of these three strains became
      infected at different times after first exposure and Helicobacter was detected by
      PCR for a brief period in the sex organs. The potential for PCR-positive tissues
      from the ovary, uterus, testis and epididymis to transmit infection was
      investigated via in vitro fertilization (IVF), embryo transfer (ET) or ovary
      transplantation in immunodeficient athymic nude-nu mice and did not result in
      contamination of the recipient females.

PMID- 16460592
TI  - Transcutaneous vascular ultrasound in hypercholesterolaemic rabbits: a new method
      to evaluate endothelial function.
AB  - Measurement of endothelial function in patients with atherosclerosis and lipid
      disorders is an important tool for the risk evaluation of a cardiovascular event,
      such as acute myocardial infarction and stroke. The feasibility of measuring
      endothelial function non-invasively in animal models has been limited so far.
      Therefore, we compared the assessment of endothelial function by in vivo
      transcutaneous vascular ultrasound (TVU) with the classical method of ex vivo
      organ bath, using the carotid artery of hypercholesterolaemic and
      normocholesterolaemic rabbits. The assessments of endothelial function by both
      techniques were performed on the same segments of the carotid artery. Vascular
      ultrasound detected impaired endothelium-dependent vasorelaxation induced by
      acetylcholine in the common carotid artery of hypercholesterolaemic rabbits.
      These results strongly correlated with measurements of endothelial function of
      isolated carotid artery rings. Furthermore, atherogenic diet caused significant
      fatty streak formation in the aorta, as well as significant increase of C
      reactive protein and cholesterol levels. Endothelial function, an early marker of
      cardiovascular risk, could be non-invasively assessed and graded by TVU
      measurements. It correlated highly with vasoreactivity of isolated vessels in an
      organ bath (r(2)=0.68). We conclude that vascular ultrasound in
      hypercholesterolaemic rabbits is a valid method for evaluating endothelial
      function associated with atherosclerosis.

PMID- 16460593
TI  - Rat embryo quality and production efficiency are dependent on gonadotrophin dose
      in superovulatory treatments.
AB  - The present study was performed to optimize a superovulation protocol in rats in
      order to produce a large number of good-quality embryos suitable to develop rat
      embryonic stem (rES) cells. We first evaluated the ovulation kinetics of three
      rat strains: Wistar, Fisher and ACI/N. Animals (n=30 per strain) were treated
      with 50 IU of pregnant mare serum gonadotrophin (PMSG), and ovulation was induced
      with 50 IU of human chorionic gonadotrophin (hCG) 50 h apart. Next, we evaluated
      the dose-response curves of PMSG and hCG in Wistar rats in order to obtain the
      highest number of embryos. The parameters evaluated for superovulation efficiency
      were: percentage of mated females, percentage of pregnant females and the average
      number of embryos collected per female. The results of these experiments
      suggested that the best dose combination was 50 IU for each hormone. Subsequent
      experiments, again with Wistar rats, were designed to test which of four hormonal
      combination treatments (30/30, 30/50, 50/30, and 50/50 IU of PMSG/hCG) will
      produce the largest numbers of good-quality embryos. Embryo quality was evaluated
      by embryo development uniformity, embryo morphology, embryo survival in an in
      vitro culture and embryo ability to generate rES-like cells. Results from these
      experiments showed that 30/50 IU of PMSG/hCG was the treatment that induced the
      best embryo quality. In conclusion, our results indicated that, in Wistar rats,
      the most appropriate hormonal combination dose for superovulation protocols with
      high number of good-quality embryos was 30 IU of PMSG and 50 IU of hCG given 50 h
      apart. We are performing further studies with rES-like cells produced with the
      present methodology to evaluate if they are able to participate in the production
      of germ-line chimeras.

PMID- 16460594
TI  - Incipient spontaneous granulosa cell tumour in the gerbil, Meriones unguiculatus.
AB  - In 167 cases of granulosa cell tumour (GCT) in the gerbil, Meriones unguiculatus,
      42.5% (71 cases) were in the ovaries, with no evidence of macroscopic lesion. In
      this paper, we describe the common findings in the incipient--microscopic--type
      of this spontaneous ovarian tumour occurring in gerbils younger than two years of
      age.

PMID- 16460595
TI  - Endotoxic shock model with fluid resuscitation in Macaca mulatta.

PMID- 16460596
TI  - Endotoxic shock model with fluid resuscitation in Macaca mulatta.

PMID- 16460597
TI  - Contamination of syringe plungers during the sampling of cyclophosphamide
      solutions.
AB  - The presence of cytotoxic agents in the urine of operators and in their
      environment has been demonstrated. The pharmacokinetics of the urinary
      elimination of cyclophosphamide suggests that these drugs are absorbed
      cutaneously during handling. In the framework of a more general study on the
      contamination of hospital environment, the present study addresses the possible
      presence of cytotoxic agents on the plungers of syringes. The report is based on
      results indicating that the bacterial contamination of a plunger may result in
      the contamination of the solution being sampled. The study was divided into two
      phases. The first phase consisted in measuring the contamination of the plungers
      of eight syringes used for handling cyclophosphamide. Cyclophosphamide was
      analysed by gas chromatography-mass spectrometry with a detection limit of 0.1
      ng/ml. The aim of the second phase was to localize the contamination on the
      plunger and thus determine the amount of drug that comes into contact with the
      gloves of the operators. The contamination was quantified by measuring the
      activity of metastable technetium. The results of the first phase showed that all
      the plungers were contaminated with cyclophosphamide amounts varying from 3.7 to
      445.7 ng. The second phase showed that the infiltration of liquid onto the
      plunger depended on the solution being sampled. Almost no infiltration was seen
      with labelled water, but contamination appeared after the first sampling of a
      cyclophosphamide solution, then increased as a function of the number of times
      the plunger was pushed in and out. These results indicate that cyclophosphamide
      solutions infiltrate onto the plungers of syringes. They suggest that the general
      procedure for handling cytotoxic agents should be modified, and a regular
      replacement of syringes should be enforced. They also partly explain why the
      gloves of 50-90% operators are contaminated after a single preparation. The
      contamination seems to depend on the type of solution sampled and the number of
      samplings. Initial investigations by the manufacturer of the syringes had shown
      that the acid pH of cyclophosphamide solutions may affect the lubricant of the
      joint. Our study demonstrates that the contamination of plungers is one of the
      sources of environmental contamination for health workers handling antineoplastic
      agents, even in the absence of manipulation errors. More generally, these results
      demonstrate that the exposure of operators cannot be clearly described unless all
      existing sources of contamination in their environment are identified. The
      implementation of suitable procedures should thus take into account all possible
      sources of contamination, including technical facilities such as the use of a
      safety cabinet or an isolator.

PMID- 16460598
TI  - Microbial growth tests in anti-neoplastic injectable solutions.
AB  - The Institut Gustave-Roussy (IGR) Department of Clinical Pharmacy (DCP) ensures
      the annual preparation of about 30 000 therapeutic batches of anti-neoplastic
      agents. High performance thin-layer chromatography (HPTLC) allows postproduction
      quality control of these batches. Although the centralized chemotherapy
      manufacturing unit has been recently ISO 9001:2000 certified, it was considered
      to improve the quality level of manufactured batches even further. The viability
      of micro-organisms (bacteria and fungi) in appropriate sterile media containing
      various anti-neoplastic agents at therapeutic concentration was assessed to
      demonstrate the lack of contamination during our manufacturing process in the
      isolator. After 14 days of incubation in these media, the results show the
      absence of contamination of the manufactured batches. This leads us to conclude
      that using sterile drugs and sterile medical devices in a sterile isolator allows
      the manufacture of sterile therapeutic batches with excellent confidence.

PMID- 16460599
TI  - Compatibility and stability of the novel anti-cancer agent C1311 in infusion
      devices and its in vitro biocompatibility.
AB  - C1311 is the lead compound from the imidazoacridinones, a novel group of
      rationally designed anti-cancer agents. The compound is pharmaceutically
      formulated as a lyophilized product containing 100 mg C1311 (anhydrous free base)
      per dosage unit and requires reconstitution before intravenous administration.
      The aim of this study was to determine the stability of C1311 in the
      reconstituted solution and infusion solution and its compatibility with infusion
      devices. Moreover, the buffer capacity and haemolytic potential of C1311 infusion
      solutions, which exhibit a relatively low pH of 2-3, were evaluated in vitro.
      C1311 was shown to be stable in the reconstituted solution for at least 48 h and
      for at least 96 h after subsequent dilution in 0.9% sodium chloride and 5%
      dextrose. In vitro infusion simulation studies showed C1311 infusion solutions to
      be compatible with a low-density polyethylene administration set. Furthermore,
      the buffer capacity and haemolysis studies showed no indications for haemolysis
      or potential for vascular irritation upon continuous infusion of C1311. In
      conclusion, C1311 lyophilized product is adequately stable and compatible after
      reconstitution and in infusion fluids to be used in the clinic and is not
      expected to cause formulation-associated side effects in the intended
      administration schedule in the forthcoming Phase I clinical study.

PMID- 16460600
TI  - Study of the effect of standardized chemotherapy order forms on prescribing
      errors and anti-emetic cost.
AB  - OBJECTIVES: Many anti-neoplastic medication errors and excessive use of serotonin
      antagonist anti-emetic agents might be prevented by the use of a standardized
      chemotherapy order form (SCOF). Several studies showing a reduction in
      prescribing errors or control of inappropriate anti-emetic use through the use of
      SCOFs have been reported. No previously published study reported SCOFs were used
      to reduce both prescribing errors and anti-emetic cost. This study attempts to
      measure these outcomes in a haematology-oncology pharmacy service. METHODS: The
      study consisted of a four-month control period, followed by a four-month test
      period following dissemination of the standardized order forms. In each period,
      prescriber errors and anti-emetic use were monitored. During the control period,
      using clinical studies from the primary literature and anti-emetic guidelines, 64
      SCOFs representing the most commonly used chemotherapy regimens in the medical
      oncology and gynaecology oncology services were developed by the haematology
      oncology pharmacy. Differences in prescribing error rate and anti-emetic cost
      were compared between each period and with the institution's historic prescribing
      error rate. RESULTS: During the control period, 1078 orders for oral and
      parenteral granisetron and ondansetron with combined total acquisition cost of
      $76 454.64 and a mean cost of $70.92 were dispensed. During the test period, the
      pharmacy dispensed 1121 orders with an acquisition cost of $73 331.61 and a mean
      cost of $65.42. A savings of $3123.03 resulted from a reduction of the amount
      prescribed in the test period. The difference in mean cost per order between the
      two periods was significant (P <0.037). Fifty-three prescribing errors out of
      3592 medication orders were detected in the control period, while 12 errors out
      of 3585 medication orders were detected during the test period. A significant
      difference(P <0.0001) was detected between the two periods. There was a
      significant difference (P <0.0001) between the control period and the
      institution's historic prescribing error rate and no difference between the test
      period and the institution's historic prescribing error rate. CONCLUSION: SCOFs
      significantly reduced serotonin antagonist anti-emetic cost and prescribing error
      rate over a four-month period.

PMID- 16460601
TI  - Polyuria associated with high-dose methotrexate in two patients with acute
      lymphoblastic leukaemia.
AB  - Although methotrexate has an established safety profile in clinical practice,
      severe morbidity can still occur on rare occasions. We report two patients with
      leukemia treated with high dose methotrexate. Both patients developed profound
      polyuria that required aggressive fluid resuscitations during the treatments.
      Renal toxicity is a known complication of methotrexate, but polyuria associated
      with its use has not been reported before. Polyuria started shortly after the
      initiation of the medicine in both patients. The polyuria resolved as the drug
      level in blood became undetectable. The episodes of polyuria were transient and
      recurred every time when the patients received methotrexate. The clinical
      pictures were not compatible with classical drug induced nephrogenic diabetes
      insipidus. It is possible that the drug interferes with adenosine metabolism,
      which in turn alters the tubular ability of solute and fluid reabsorption.

PMID- 16460602
TI  - Accidental intrathecal injection of vincristine.

PMID- 16460604
TI  - Pharmaceutical validation as a process of improving the quality of antineoplastic
      treatment.
AB  - OBJECTIVE: To quantify the improvement added by standardization of pharmaceutical
      validation (PV) of antineoplastic treatment to the processes of prescription and
      preparation of the pharmacotherapeutic sequence, in terms of prevention and
      reduction of medication errors (ME). DESIGN: Prospective cohort study during two
      years (from 2001-2002) for oncohaematologic patients (inpatients and outpatients)
      that compared the percentage of medication errors detected and resolved and the
      number of medication errors with potential clinical significance (severity value
      >or=4) intercepted during PV in both years. RESULTS: During the PV processes, 202
      ME were identified and resolved, which is the equivalent of 16.88 ME/1,000
      patient-days. In 2001 14.08 ME/1,000 patient-days were detected and 19.83
      ME/1,000 patient-days in 2002. This means that the effectiveness of the
      identification method increased by 41%. The number of ME intercepted with
      clinical significance (severity value >or=4) increased in a statistically
      significant manner by 2.18 times in 2002. CONCLUSION: This study shows that the
      standardization of PV is an effective method of improving the quality of
      antineoplastic treatment use, by increasing the ability to intercept ME.

PMID- 16460603
TI  - Assessment of ovarian failure and osteoporosis in premenopausal breast cancer
      survivors.
AB  - Premenopausal women who develop ovarian failure after receiving chemotherapy are
      at a higher risk of rapid bone loss. Pharmacists have successfully implemented
      osteoporosis screening programmes in the general population and thus, assessment
      of breast cancer survivors for ovarian failure and osteopenia could represent a
      novel focus for oncology pharmacists. Therefore, we conducted a retrospective
      chart review to determine the adequacy of ovarian failure and osteoporosis
      assessment and management in premenopausal breast cancer survivors. METHODS AND
      RESULTS: The charts of 20 women diagnosed with early stage breast cancer treated
      with cyclophosphamide over a 4.5-year timespan were included. Their median age
      was 36.7 years (range 29.8-41). The median cyclophosphamide cumulative dose was 9
      g/m(2) (range 2.4-14.45), with a median duration of follow-up being 4.62 years.
      The assessment of ovarian failure mainly occurred by documenting menstrual
      periods, which has been questioned as a reliable method for assessing ovarian
      failure. Menses stopped while or shortly after receiving chemotherapy in 11
      women. Prior to and during cyclophosphamide administration, osteoporosis
      screening or counselling was not documented for any patient. After completion of
      chemotherapy administration, eight patients were counselled regarding
      osteoporosis and seven women were screened for osteoporosis with a dual X-ray
      absorptimetry (DXA) scan. Five women had DXA scans indicative of osteopenia
      according to World Health Organization guidelines. CONCLUSIONS: Improvements are
      needed in the documentation and potentially also the management of ovarian
      failure and osteoporosis in premenopausal breast cancer survivors receiving
      cyclophosphamide-based regimens. This represents a potential opportunity for
      pharmacists to manage long-term chemotherapy toxicity.

PMID- 16460605
TI  - Alendronate for steroid-induced osteopenia in children with acute lymphoblastic
      leukaemia or non-Hodgkin's lymphoma: results of a pilot study.
AB  - BACKGROUND/OBJECTIVES: Osteopenia is a significant morbidity in children
      undergoing therapy for acute lymphoblastic leukaemia (ALL) or non-Hodgkin's
      lymphoma (NHL). We conducted a pilot study to assess the impact of alendronate on
      whole body bone mineral content (WB-BMC), lumbar spine bone mineral density (LS
      BMD), biochemical measures of bone mineral metabolism, as well as gross motor
      function and health-related quality of life (HRQL) in children undergoing therapy
      for ALL or NHL. METHODS: Ten children (nine boys) between the ages of 3.6 and
      14.6 years, on identical maintenance chemotherapy for ALL or NHL were treated
      with oral alendronate once weekly, and daily calcium supplementation, for a
      period of six months. Outcome measures were WB-BMC and LS-BMD; biochemical
      measures of bone mineral metabolism including plasma osteocalcin, C-terminal
      telopeptide of type I collagen (CTx), serum calcium, 25-hydroxy-vitamin D (25
      OHD), and parathyroid hormone (PTH); as well as assessments of motor function and
      HRQL. RESULTS: A gain in Z score was observed in 7/9 evaluable patients for WB
      BMC (mean increase of 0.49) and LS-BMD (0.51). Plasma osteocalcin and CTx showed
      a change in bone turnover favouring formation over resorption. Serum calcium and
      25-OHD remained normal throughout treatment. After an initial spike, serum PTH
      returned to baseline values at week 4. Measures of motor function showed some
      improvement and there were modest gains in HRQL. CONCLUSIONS: Alendronate therapy
      was tolerated well. Further study in a larger sample of children with ALL or NHL
      is warranted, in the context of a randomized clinical trial.

PMID- 16460606
TI  - Sterility validity period of vials after multiple sampling under vertical laminar
      airflow hood.
AB  - STUDY OBJECTIVES: The aim of this study is to validate the sterility period of
      vials after multiple sampling under Grade A vertical laminar airflow hood.
      METHODS: Vials filled aseptically with a sterile culture medium have been sampled
      with syringes three times a week over one month under Grade A vertical laminar
      airflow hood and in the mean-while, keeping the vials out of the laminar airflow
      hoods. RESULTS: No microbial growth has been observed. On the basis of these
      results, it has been decided to modify our standard operating procedures, to
      allow keeping the vials for two weeks in a box out of the laminar airflow hoods
      (ambient temperature Grade B) or any controlled environment (under
      refrigeration). CONCLUSIONS: This study validates the multiple use of vials of
      small to large volumes (5-100 mL), to simplify handling and to reduce the costs
      in centralized cytostatic reconstitution units in hospital pharmacies, with no
      microbial risk.

PMID- 16460607
TI  - A reporting system for the assessment of chemotherapy toxicity.
AB  - PURPOSE: Toxicity may distress patients and cause delay or a discontinuance of
      scheduled chemotherapies. A key issue is to create a reporting system in order to
      assess toxicities and also evaluate treatments. METHODS: In the Oncology Unit
      3,000 intravenous chemotherapies are administered each year, mostly in the day
      hospital. In summer 2002, oncologists and pharmacists agreed to assess
      myelosuppression and gastrointestinal toxicity of grades 3 and 4. Pharmacists
      designed a form and a database in order to collect toxicity data for every
      patient. The oncologist records type and grade of toxicity (according to the NCI
      CTC) on the patient chart before chemotherapy commences. During the validation of
      computerized prescriptions the pharmacist collects data about possible toxicities
      of every grade. RESULTS: From August-October 2002, 675 chemotherapies were
      administered. Seventy-two patients developed GI toxicity at various grades, nine
      of grade 3 and two of grade 4. Regimens with fluorouracil, carboplatin, cisplatin
      and oxaliplatin were highly involved in GI toxicity. Eighty-seven patients
      developed myelosuppression, two of grade 3 and 33 of grade 4. Regimens with
      epirubicin, cyclophosphamide, paclitaxel, cisplatin and carboplatin were highly
      involved in myelosuppression. After the first report, oncologists and pharmacists
      decided to stop collecting data in order to improve the reporting system and to
      plan regular meetings. CONCLUSIONS: A reliable reporting system is a valuable
      tool for oncologists to manage toxicity and to evaluate chemotherapy regimens.
      Assessing chemotherapy toxicity is a good opportunity for pharmacists to take
      part in preventing toxicity and reducing patient's discomfort.

PMID- 16460608
TI  - Vinorelbine and venous irritation: optimal parenteral administration.
AB  - Vinorelbine is a vesicant associated with extra-vasation hazards and injection
      site reactions, which can be alleviated by shortening of infusion time and
      flushing of intravenous fluid. A critical review of the current evidence showed
      that the optimal administration is to flush >or= 75-124 mL of intravenous fluid
      after vinorelbine infusion. Intravenous push administration over 1-2 min does not
      seem to offer significant improvement over rapid intravenous infusion over 6-10
      min.

PMID- 16460628
TI  - Management of Dupuytren's disease--clear advice for an elusive condition.
AB  - Dupuytren's disease is a progressive fibroproliferative disorder of an unknown
      origin affecting the hands causing permanent flexion contracture of the digits.
      Significant risk factors for development of Dupuytren's disease include old age,
      male sex, white northern European extraction, presence of positive family history
      of Dupuytren's disease, and diabetes mellitus. The disease also seems to
      deteriorate rapidly in those cases showing young age of onset and additional
      fibromatosis affecting the back of the hands, soles of the feet and the penis.
      Although there is no cure, patients with Dupuytren's disease of the hand may gain
      a significant functional benefit following surgical improvement or correction of
      the deformity. With realistic expectations, timely and appropriate surgical
      technique in a specialist centre, and attention to postoperative recovery and
      rehabilitation (occupational therapy and physiotherapy support), a beneficial
      outcome can be achieved in most cases.

PMID- 16460629
TI  - Achalasia of the cardia: dilatation or division? The case for balloon dilatation.

PMID- 16460630
TI  - Hand washing rituals in trauma theatre: clean or dirty?
AB  - INTRODUCTION: The aim of this study was to investigate the degree of
      contamination of a surgeon's hand following use of chlorhexidine gluconate or
      alcohol gel as disinfectants. MATERIALS AND METHODS: In this prospective,
      randomised trial, orthopaedic surgeons were allocated to one of two different
      hand-washing protocols using a randomisation table. The hand-washing protocol
      dictated that all surgeons should wash for 5 min with chlorhexidine for their
      first case. Thereafter, the surgeon was randomised to wash for 3 min with either
      alcohol gel or chlorhexidine. At the end of each procedure, the gloves of each
      surgeon were carefully removed and the fingertips from each hand were placed on
      an agar plate. The number of bacterial colonies present after 24 h and 48 h of
      incubation were recorded for each agar plate by a microbiologist blinded to the
      washing protocol used. RESULTS: Overall, 41 procedures and 82 episodes of hand
      washings were included in the study. Two episodes were discarded due to
      contamination at the time of glove removal. Four hands (8%) were contaminated in
      the chlorhexidine group compared to 19 (34%) in the alcohol group. Fisher's exact
      test confirmed a significantly higher risk of contamination using alcohol gel
      compared to chlorhexidine (P = 0.002). In addition, the average bacterial colony
      count was substantially higher in the alcohol group (20 colony forming units)
      compared to the chlorhexidine group (5 colony forming units). There was no
      relationship between the duration of surgery and the degree of contamination (P =
      1.12). CONCLUSIONS: Alcohol gel disinfectant is not a suitable alternative to
      chlorhexidine when hand washing before surgery. This study has identified a
      higher risk of bacterial contamination of surgeons' hands washed with alcohol.
      This may lead to higher levels of postoperative infection in the event of glove
      perforation.

PMID- 16460631
TI  - Magnetic tracking: a novel method of assessing anterior cruciate ligament
      deficiency.
AB  - INTRODUCTION: The Lachman test is commonly performed as part of the routine
      assessment of patients with suspected anterior cruciate ligament (ACL)
      deficiency. A major drawback is its reliance on the clinician's subjective
      judgement of movement. The aim of this study was to quantify Lachman movement
      using a magnetic tracking device thereby providing a more accurate objective
      measure of movement. PATIENTS AND METHODS: Ten patients aged 21-51 years were
      assessed as having unilateral ACL deficiency with conventional clinical tests.
      These patients were then re-assessed using a Polhemus Fastrak magnetic tracking
      device. RESULTS: The mean anterior tibial displacement was 5.6 mm (SD = 2.5) for
      the normal knees and 10.2 mm (SD = 4.2) for the ACL-deficient knees. This gave an
      82% increase in anterior tibial displacement for the ACL deficient knees. This
      was shown to be highly significant with P = 0.005. CONCLUSIONS: The magnetic
      tracking system offers an objective quantification of displacements during the
      Lachman test. It is convenient, non-invasive and comfortable for the patient and
      is, therefore, ideally suited for use as an investigative tool.

PMID- 16460632
TI  - A prospective, randomised, controlled trial comparing wound dressings used in hip
      and knee surgery: Aquacel and Tegaderm versus Cutiplast.
AB  - INTRODUCTION: Cutiplast (absorbent perforated dressing with adhesive border;
      Smith & Nephew) is commonly used following orthopaedic operation, but
      complications of its use have been reported. A prospective, randomised,
      controlled study was performed to compare the efficacy of Cutiplast versus an
      Aquacel (hydrofibre dressing; ConvaTec) covered with Tegaderm (vapour-permeable
      dressing; 3M). PATIENTS AND METHODS: Two-hundred patients were randomised to
      receive one of the two dressings following elective and non-elective surgery of
      the hip and the knee. We were able to study 183 patients. The condition of the
      wound and any complications such as skin blistering or signs of infection was
      noted as was the frequency of dressing changes. RESULTS: The Aquacel and Tegaderm
      dressing was 5.8 times more likely to result in a wound with no complications as
      compared to a Cutiplast dressing (odds ratio, 5.8; 95% CI 2.8-12.5; P < 0.00001).
      CONCLUSION: Aquacel covered by Tegaderm is a superior dressing to Cutiplast
      following surgery to the hip and knee.

PMID- 16460633
TI  - Plain abdominal radiographs: can we interpret them?
AB  - INTRODUCTION: Plain abdominal radiographs commonly form a part of medical
      assessments. Most of these films are interpreted by the clinicians who order
      them. Interpretation of these films plays an important diagnostic role and,
      therefore, influences the decision for admission and subsequent management of
      these patients. The aim of this study was to find out how well doctors in
      different specialties and grades interpreted plain abdominal radiographs.
      MATERIALS AND METHODS: A total of 76 doctors from the Departments of Accident &
      Emergency, Medicine, Surgery and Radiology (17, 32, 23 and 4, respectively)
      participated in the study which involved giving a diagnosis for each of 14 plain
      abdominal radiographs (5 'normal' and 9 'abnormal'). They were also asked the
      upper limit of normal dimensions of small bowel and large bowel. One point was
      awarded for correctly identifying whether a radiograph was normal/abnormal, 1
      point for the correct diagnosis and 1 point for the correct bowel dimensions,
      giving a total score of 30. RESULTS: Mean scores out of 30 for specialties were
      as follows: Accident & Emergency 13.1 (range, 2-22), Medicine 11.2 (range, 2-23),
      Surgery 15.0 (range, 8-24) and Radiology 17.0 (range, 14-20; P = 0.241). Mean
      scores out of 30 for different grades of doctors were as follows: pre
      registration house officers 10.8 (range, 4-20), senior house officers 13.0
      (range, 2-22), registrars/staff grades 13.8 (range, 2-23) and consultants 17.3
      (range, 12-24; P = 0.028). Fifteen out of 76 (19.7%) doctors correctly identified
      the upper limit of normal dimension of small bowel; 24 out of 76 (31.6%)
      correctly identified the upper limit of normal dimension of large bowel.
      DISCUSSION: The level of seniority positively correlated with skills of plain
      abdominal radiograph interpretation. A large number of doctors were unable to
      give the correct upper limit of normal dimensions for small and large bowel.
      CONCLUSIONS: All doctors could benefit from further training in the
      interpretation of plain abdominal radiographs. This could perhaps take place as
      formal teaching sessions and be included in induction programmes. Until then,
      plain abdominal films should ideally be reported by radiologists where there are
      clinical uncertainties; important management decisions made by junior doctors
      based on these films should at least be confirmed with a registrar, if not a
      consultant.

PMID- 16460634
TI  - Diagnosis and conservative treatment of tubercular rectoprostatic fistula.
AB  - OBJECTIVE: To present our experience with three cases of rectoprostatic fistula
      with special emphasis on diagnosis and conservative management. PATIENTS AND
      METHODS: Three middle-aged men presented to us differently. All had spontaneous
      rectoprostatic fistulas. Biopsy showed tuberculosis though three consecutive
      urine samples for acid-fast bacilli were negative. None of the patients were
      immunocompromised. Their upper tracts were normal and all had a past history of
      pulmonary tuberculosis. They were started on antitubercular drugs and urinary
      diversion with or without faecal diversion. RESULTS: All fistulae healed
      completely within 6 weeks of starting antitubercular treatment. One patient
      healed with bladder neck stenosis that required bladder neck incision. Voiding
      was normal on 1-year follow-up. CONCLUSION: Spontaneous tubercular rectoprostatic
      fistulae are rare. There should be a strong clinical suspicion in endemic areas.
      Prostatic biopsy proves the diagnosis. Conservative management with
      antitubercular drugs and urinary diversion with or without faecal diversion has a
      high success rate and should be the first line of treatment even if urine is
      negative for acid-fast bacilli.

PMID- 16460635
TI  - Do patients with frank haematuria referred under the two-week rule have a higher
      incidence of bladder cancer?

PMID- 16460636
TI  - Patients with clinical acute appendicitis should have pre-operative full blood
      count and C-reactive protein assays.
AB  - INTRODUCTION: The role of inflammatory markers in the diagnosis of acute
      appendicitis has not been clearly defined. The aims of this prospective audit
      were to define the role of the serum markers of inflammation total white cell
      count, neutrophil count and C-reactive protein in the diagnosis of acute
      appendicitis with particular reference to the discrimination between
      uncomplicated and complicated appendicitis, and the prediction of abscess.
      PATIENTS AND METHODS: The author compiled a prospective database over a 13-month
      period of all appendicectomies performed. After five exclusions (three having no
      notes for review and two having confounding second morbidity in the presence of a
      normal appendix), the data relating to 75 patients were analysed. RESULTS: In
      patients judged on clinical grounds to require laparotomy for suspected acute
      appendicitis, white cell count and neutrophil count distinguish acute
      appendicitis from normal appendices when used as categorical variables, though
      they do not reflect the presence of abscess. C-reactive protein neither
      distinguishes appendicitis from normal, nor predicts abscess when used as a
      categorical variable, though higher levels suggest abscess. CONCLUSIONS:
      Laboratory tests of the white cell count, neutrophil count and C-reactive protein
      are more effective in supporting a clinical diagnosis of acute appendicitis in
      patients with typical clinical features than in excluding the diagnosis.

PMID- 16460637
TI  - Gauze packing of open surgical wounds: empirical or evidence-based practice?
AB  - INTRODUCTION: Most surgical wounds are closed primarily, but some are allowed to
      heal by secondary intention. This usually involves repeated packing and dressing
      of the raw wound surfaces. Although the long-term care of such wounds has
      devolved to the care of nurses in the community or out-patient setting, the
      initial wound dressing or cavity packing is done by the surgeon in the operating
      theatre. Many surgeons are unaware of the growth of the discipline of wound care,
      and still use traditional soaked gauze for dressing and packing open surgical
      wounds and cavities. RESULTS: This review summarises the some of the modern
      alternatives available and the evidence--or the lack of it--for their use in both
      the acute and chronic setting.

PMID- 16460638
TI  - Surgical treatment of varicose veins: effect of rationing.
AB  - INTRODUCTION: A substantial part of vascular surgical workload is devoted to the
      treatment of varicose veins. To control demand for cosmetic venous surgery,
      primary care trusts in Somerset introduced clinical criteria in 2000 for the
      referral and treatment of varicose veins based on the presence of skin change or
      ulceration, a history of bleeding, or two or more episodes of thrombophlebitis.
      PATIENTS AND METHODS: A comparison of workload and case mix for the referral and
      treatment of new patients presenting with varicose veins to the Taunton and
      Somerset Hospital was carried out over two 6-month periods, before and after the
      introduction of clinically based assessment criteria. RESULTS: A total of 134
      operations for varicose veins were carried out in 2000 and 85 such operations in
      2002/03 after the introduction of new referral criteria (P = 0.001). Of these,
      69% (92/134) were day-case procedures in 2000 compared to only 48% (41/85) in
      2002/03 (P = 0.004). There was no significant difference in the type of cases
      (e.g. single, bilateral or recurrent surgery) performed as a day-case (P = 0.34)
      or as an in-patient (P = 0.43) over the two periods. There was, however, a
      significant difference (P = 0.007) in the mean ages of patients in the two
      periods (48.5 years in period 1; 57.8 years in period 2) and in the average ASA
      grade (1.15 in period 1; 1.42 in period 2; P = 0.0002). CONCLUSION: The
      introduction of clinical criteria for the referral and treatment of varicose
      veins reduced workload by 37%.

PMID- 16460639
TI  - Can we rely on a general practitioner's referral letter to a skin lesion clinic
      to prioritize appointments and does it make a difference to the patient's
      prognosis?
AB  - INTRODUCTION: This study was designed to: (i) determine if the priority of
      referral letters by general practitioners to a plastic surgery skin lesion clinic
      adhered to the national guidelines, what happened to these patients, and what was
      the histological diagnosis; and (ii) analyse whether the prognosis at diagnosis
      of malignant melanoma had improved since the introduction of the 2-week wait for
      patients with suspected cancer. MATERIALS AND METHODS: The study involved a
      prospective audit questionnaire, retrospective note review and histology report
      review in the Plastic Surgery Department in a district general hospital and their
      'bespoke' out-patient clinics. RESULTS: Of 202 referral letters, 58 (29%) were
      referred as 2-week cancer referrals of which 13 (22%) suggested diagnoses that
      did not fall within the guidelines, and 11 gave no diagnosis. In addition, 84
      (42%) had no indication of priority, though the text may suggest the need for it,
      either explicitly or implied. The prognostic indices for malignant melanoma have
      not altered since the 2-week wait rule has been implemented. CONCLUSIONS: The
      guidelines are not being adhered to, thus patients with benign lesions are being
      given undue priority. The history and examination of skin lesions given in the
      referral letters is insufficient to allow the consultant to prioritize. Since the
      2-week rule has be implemented, malignant melanomas have not been diagnosed at an
      earlier stage.

PMID- 16460640
TI  - Prevalence of HIV status and CD4 counts in a surgical cohort: their relationship
      to clinical outcome.
AB  - INTRODUCTION: HIV positivity alone as a predictor of surgical outcome has not
      been extensively studied in regions of high prevalence. The aim was to determine
      the prevalence of HIV infection in surgical patients, and compare differences in
      their clinical course based on their serological status and CD4 counts. PATIENTS
      AND METHODS: A prospective cohort of 350 patients, enrolled over 6 weeks, were
      studied. HIV status was determined in all patients. HIV-positive patients had CD4
      counts. Clinical details were collated with HIV data after completion of
      enrollment. RESULTS: Of the 350 patients, all but 6 were black South Africans.
      The median age was 31 years (range, 18-82 years). There were 143 trauma and 207
      non-trauma patients. The male:female ratio was 1.4:1. The overall HIV
      seropositivity rate was 39% (females, 46%; males, 36%). Overall, 228 patients had
      surgical intervention and 96 patients had drainage of sepsis. The hospital stay
      (HIV negative, 11.9 +/- 15.9 days; HIV positive, 11.0 +/- 15 days) and mortality
      (HIV positive, 3.6%; HIV negative, 3.7%) did not differ by major diagnostic
      category. For HIV-positive patients, the male:female ratio was 1.2:1. There were
      54 trauma and 83 non-trauma patients. An operation for the drainage of a septic
      focus was commoner in the HIV-positive admissions. Thirty-two (24%) patients had
      CD4 counts less than 200 cells/mm3, (i.e. AIDS). The hospital mortality, hospital
      stay and severity of sepsis were not related to CD4 counts. CONCLUSIONS: HIV
      status does not influence the outcome of general surgical admissions and should
      not influence surgical management decisions. In HIV-positive surgical patients,
      CD4 counts have no relation to in-hospital outcome in a heterogeneous group of
      surgical patients.

PMID- 16460641
TI  - Is there a role for the intravenous urogram in the 21st century?
AB  - Over the last two decades, there have been major advances in methods of medical
      imaging that have brought great benefits to patients both for diagnosis and for
      treatment. There has been an increasing tendency for some of these new imaging
      modalities to be dependent on highly sophisticated technology. The belief has
      developed amongst doctors who use these techniques that newer is necessarily
      better. Just as patients (and some doctors) now often believe that anything done
      with a laser represents the best that can be offered, so there is a tendency to
      demand that newer techniques in imaging should always be offered as the preferred
      option. In urological practice that philosophy is questionable.

PMID- 16460643
TI  - Management of patients with prostate cancer.

PMID- 16460644
TI  - Theatre shoes--taking them one day at a time.

PMID- 16460646
TI  - Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles
      for inherited hearing loss in the Palestinian population.
AB  - Recessively inherited phenotypes are frequent in the Palestinian population, as
      the result of a historical tradition of marriages within extended kindreds,
      particularly in isolated villages. In order to characterise the genetics of
      inherited hearing loss in this population, we worked with West Bank schools for
      the deaf to identify children with prelingual, bilateral, severe to profound
      hearing loss not attributable to infection, trauma or other known environmental
      exposure. Of 156 families enrolled, hearing loss in 17 families (11 per cent) was
      due to mutations in GJB2 (connexin 26), a smaller fraction of GJB2-associated
      deafness than in other populations. In order to estimate how many different genes
      might be responsible for hearing loss in this population, we evaluated ten
      families for linkage to all 36 known human autosomal deafness-related genes,
      fully sequencing hearing-related genes at any linked sites in informative
      relatives. Four families harboured four novel alleles of TMPRSS3 (988DeltaA =
      352stop), otoancorin (1067A > T = D356V) and pendrin (716T > A = V239D and 1001G
      > T = 346stop). In each family, all affected individuals were homozygous for the
      critical mutation. Each allele was specific to one or a few families in the
      cohort; none were widespread. Since epidemiological tests of association of
      mutations with deafness were not feasible for such rare alleles, we used
      functional and bioinformatics approaches to evaluate their consequences. In six
      other families, hearing loss was not linked to any known gene, suggesting that
      these families harbour novel genes responsible for this phenotype. We conclude
      that inherited hearing loss is highly heterogeneous in this population, with most
      extended families acting as genetic isolates in this context. We also conclude
      that the same genes are responsible for hearing loss in this population as
      elsewhere, so that gene discovery in these families informs the genetics of
      hearing loss worldwide.

PMID- 16460647
TI  - Inference of ancestry: constructing hierarchical reference populations and
      assigning unknown individuals.
AB  - The ability to infer personal genetic ancestry is being increasingly utilised in
      certain medical and forensic situations. Herein, the unsupervised Bayesian
      clustering algorithms structure, is employed to analyse 377 autosomal short
      tandem repeats typed on 1,056 individuals from the Centre d'Etude du
      Polymorphisme Humain Human Diversity Panel. Individuals of known geographical
      origin were hierarchically classified into a framework of increasingly
      homogeneous clusters to serve as reference populations into which individuals of
      unknown ancestry can be assigned. The groupings were characterised by the
      geographical affinities of cluster members and the accuracy of these procedures
      was verified using several genetic indices. Fine-scale substructure was
      detectable beyond the broad population level classifications that previously have
      been explored in this dataset. Metrics indicated that within certain lines, the
      strongest structuring signals were detected at the leaves of the hierarchy where
      lineage-specific groupings were identified. The accuracy of unknown assignment
      was assessed at each level of the hierarchy using a 'leave one out' strategy in
      which each individual was stripped of cluster membership and then re-assigned
      using the supervised Bayesian clustering algorithm implemented in GeneClass2.
      Although most clusters at all levels of resolution experienced highly accurate
      assignment, a decline was observed in the finer levels due to the mixed
      membership characteristics of some individuals. The parameters defined by this
      study allowed for assignment of unknown individuals to genetically defined
      clusters with measured likelihood. Shared ancestry data can then be inferred for
      the unknown individual.

PMID- 16460648
TI  - FDA perspectives on potential microarray-based clinical diagnostics.
AB  - The US Food and Drug Administration (FDA) encourages the development of new
      technologies such as microarrays which may improve and streamline assessments of
      safety and the effectiveness of medical products for the benefit of public
      health. The FDA anticipates that these new technologies may offer the potential
      for more effective approaches to medical treatment and disease prevention and
      management. This paper discusses issues associated with the translation of
      nucleic acid microarray-based devices from basic research and target discovery to
      in vitro clinical diagnostic use, which the Office of In Vitro Diagnostic Device
      Evaluation and Safety in the Center for Devices and Radiological Health foresees
      will be important for assurance of safety and effectiveness of these types of
      devices. General technological points, assessment of potential concerns for
      transitioning microarrays into clinical diagnostic use and approaches for
      evaluating the performance of these types of devices will be discussed.

PMID- 16460649
TI  - Immunogenomics: molecular hide and seek.
AB  - Similar to other classical science disciplines, immunology has been embracing
      novel technologies and approaches giving rise to specialised sub-disciplines such
      as immunogenetics and, more recently, immunogenomics, which, in many ways, is the
      genome-wide application of immunogenetic approaches. Here, recent progress in the
      understanding of the immune sub-genome will be reviewed, and the ways in which
      immunogenomic datasets consisting of genetic and epigenetic variation, linkage
      disequilibrium and recombination can be harnessed for disease association and
      evolutionary studies will be discussed. The discussion will focus on data
      available for the major histocompatibility complex and the leukocyte receptor
      complex, the two most polymorphic regions of the human immune sub-genome.

PMID- 16460650
TI  - Mitochondrial DNA as a potential tool for early cancer detection.
AB  - The recent surge in mitochondrial research has been driven by the identification
      of mitochondria-associated diseases and the role of mitochondria in apoptosis.
      Both of these aspects have identified mitochondrial analysis as a vital component
      of medical research. Moreover, mitochondria have been implicated in the process
      of carcinogenesis because of their vital role in energy production, nuclear
      cytoplasmic signal integration and control of metabolic pathways. Interestingly,
      at some point during neoplastic transformation, there is an increase in reactive
      oxygen species, which damage the mitochondrial genome. This accelerates the
      somatic mutation rate of mitochondrial DNA. It has been proposed that these
      mutations may serve as an early indication of potential cancer development and
      may represent a means for tracking tumour progression. The purpose of this review
      is to explore the potential utility that these mutations may afford for the
      identification and monitoring of neoplasia and malignant transformation where
      appropriate body fluids or non-invasive tissue access is available for
      mitochondrial DNA recovery. Specifically, prostate, breast, colorectal, skin and
      lung cancers are discussed.

PMID- 16460651
TI  - Integrated analysis of genetic data with R.
AB  - Genetic data are now widely available. There is, however, an apparent lack of
      concerted effort to produce software systems for statistical analysis of genetic
      data compared with other fields of statistics. It is often a tremendous task for
      end-users to tailor them for particular data, especially when genetic data are
      analysed in conjunction with a large number of covariates. Here, R (http://www.r
      project.org), a free, flexible and platform-independent environment for
      statistical modelling and graphics is explored as an integrated system for
      genetic data analysis. An overview of some packages currently available for
      analysis of genetic data is given. This is followed by examples of package
      development and practical applications. With clear advantages in data management,
      graphics, statistical analysis, programming, internet capability and use of
      available codes, it is a feasible, although challenging, task to develop it into
      an integrated platform for genetic analysis; this will require the joint efforts
      of many researchers.

PMID- 16460653
TI  - Take-off activity and orientation of triatomines (Heteroptera: Reduviidae) in
      relation to the presence of artificial lights.
AB  - We analysed the flying activity of Triatoma infestans and Rhodnius prolixus when
      confronted to artificial lights of different spectral quality. We found that the
      presence of light sources (white or ultraviolet) did not affect their spontaneous
      take-off rate. The comparison between species showed that R. prolixus was more
      prone to fly than T. infestans. Females of T. infestans initiated flight more
      frequently than males of the same species. Although the same tendency was
      observed in R. prolixus, no significant differences were assessed between sexes.
      Concerning the orienting behaviour of triatomines at take-off in relation to the
      position of the light source, T. infestans showed a significant tendency to fly
      towards white light, but a non-oriented response when confronted to UV light or
      in the absence of a light source. R. prolixus also preferred to fly towards a
      source of white light and exhibited a non-oriented response with no light.
      However, when the UV light was presented, these bugs exhibited a bimodal
      attraction/repellence-behaviour. Our results support true attraction by white
      light rather than menotaxis or arrival by chance. These findings are discussed in
      relation to the colonization of human dwellings by Chagas disease vectors.

PMID- 16460654
TI  - Altitudinal structuring of sand flies (Diptera: Psychodidae) in the High-Atlas
      mountains (Morocco) and its relation to the risk of leishmaniasis transmission.
AB  - This paper presents the results of entomological surveys on phlebotomine sand
      flies (Diptera: Psychodidae) in the Haouz of Marrakech and High-Atlas mountains
      (Morocco). Sand flies were captured with sticky traps from 25 stations with
      altitudes ranging between 400 and 1400 m. A total of 2742 specimens belonging to
      nine phlebotomine species was collected, Phlebotomus (Larroussius) perniciosus
      Newstead being the predominant species. There was a remarkable difference in the
      diversity of the sand fly fauna among the altitudes. Two associations of sand fly
      faunas were determined, the first one in lower altitude and the second one in
      higher altitude. The significance of the predominant species at any altitude
      range was discussed in terms of the risk of transmission of leishmaniasis.

PMID- 16460655
TI  - Secondary structures of proteins adsorbed onto aluminum hydroxide: infrared
      spectroscopic analysis of proteins from low solution concentrations.
AB  - Comparative studies of the secondary structures of six model proteins, adsorbed
      onto aluminum hydroxide gel (Alhydrogel) or in aqueous solution, were carried out
      by Fourier transform infrared (FTIR) spectroscopy. The analysis of high-quality
      spectra of all six model proteins, with a broad range of secondary structure
      compositions, obtained at 15 mg/ml by the conventional method and at 0.5 and 1.0
      mg/ml adsorbed to Alhydrogel revealed that adsorption onto hydrophilic surfaces
      of aluminum hydroxide particles did not alter the secondary structures of the
      proteins. The results of this study suggest that adsorbing proteins to Alhydrogel
      provides a means of obtaining FTIR spectra to study secondary structure and
      conformational changes of proteins in aqueous solution at very low
      concentrations. The new procedure effectively lowers the concentration
      requirement for FTIR studies of proteins in aqueous solutions by at least 40
      fold, as compared with the conventional FTIR method. It permits FTIR study of
      proteins to be carried out in the same concentration range as is used for
      circular dichroism and fluorescence, thereby making it possible to compare
      structural information obtained by three commonly used techniques in protein
      biophysical characterization.

PMID- 16460656
TI  - Tips for extracting total RNA from chondrocytes cultured in agarose gel using a
      silica-based membrane kit.

PMID- 16460652
TI  - Comparison of human (and other) genome browsers.
AB  - The sequence of the human genome provides a scaffold on which numerous
      annotations, such the locations of genes, can be laid. Genome browsers have been
      created to allow the simultaneous display of multiple annotations within a
      graphical interface. In addition, they provide the ability to search for markers
      and sequences, to extract annotations for specific regions or for the whole
      genome and to act as a central starting point for genomic research. This review
      describes the basic functionality of genome browsers and compares three of them:
      the University of California Santa Cruz (UCSC) Genome Browser, the Ensembl Genome
      Browser and the NCBI MapViewer.

PMID- 16460657
TI  - On the possibility of applying noncovalent dyes for protein labeling in
      isoelectric focusing.
AB  - Noncovalent fluorescent dyes are widely used for protein quantification and
      postcolumn detection in electrophoretic separations and recently some attempts to
      separate the precolumn labeled proteins using isoelectric focusing (IEF) have
      been made. In the present study, the possibility of applying the technique of
      protein labeling with noncovalent dyes for IEF is investigated. We found that
      fluorescent signal emitted by NanoOrange dye increases essentially in presence of
      carrier ampholyte (CA) components, which makes problematic a reliable protein
      detection in CA environment. Since in an isoelectric focusing mode the CA species
      are present in much greater concentration than the concentrations of fractionated
      proteins, the method of protein labeling with NanoOrange is not suitable for
      precolumn labeling and cannot be used for CA-IEF, at least without more detailed
      study of the dye-protein interaction mechanism.

PMID- 16460658
TI  - A fluorescence polarization assay for inhibitors of Hsp90.
AB  - Hsp90 encodes a ubiquitous molecular chaperone protein conserved among species
      which acts on multiple substrates, many of which are important cell-signaling
      proteins. Inhibition of Hsp90 function has been promoted as a mechanism to
      degrade client proteins involved in tumorigenesis and disease progression.
      Several assays to monitor inhibition of Hsp90 function currently exist but are
      limited in their use for a drug discovery campaign. Using data from the crystal
      structure of an initial hit compound, we have developed a fluorescence
      polarization assay to monitor binding of compounds to the ATP-binding site of
      Hsp90. This assay is very robust (Z' > 0.9) and can detect affinity of compounds
      with IC50s to 40 nM. We have used this assay in conjunction with cocrystal
      structures of small molecules to drive a structure-based design program aimed at
      the discovery and optimization of a novel class of potent Hsp90 inhibitors.

PMID- 16460659
TI  - An enzyme-coupled continuous spectrophotometric assay for S-adenosylmethionine
      dependent methyltransferases.
AB  - Modification of small molecules and proteins by methyltransferases affects a wide
      range of biological processes. Here, we report an enzyme-coupled continuous
      spectrophotometric assay to quantitatively characterize S-adenosyl-L-methionine
      (AdoMet/SAM)-dependent methyltransferase activity. In this assay, S-adenosyl-L
      homocysteine (AdoHcy/SAH), the transmethylation product of AdoMet-dependent
      methyltransferases, is hydrolyzed to S-ribosylhomocysteine and adenine by
      recombinant S-adenosylhomocysteine/5'-methylthioadenosine nucleosidase
      (SAHN/MTAN, EC 3.2.2.9). Subsequently, adenine generated from AdoHcy is further
      hydrolyzed to hypoxanthine and ammonia by recombinant adenine deaminase (EC
      3.5.4.2). This deamination is associated with a decrease in absorbance at 265 nm
      that can be monitored continuously. Coupling enzymes are recombinant and easily
      purified. The utility of this assay was shown using recombinant rat protein
      arginine N-methyltransferase 1 (PRMT1, EC 2.1.1.125), which catalyzes the mono-
      and dimethylation of guanidino nitrogens of arginine residues in select proteins.
      Using this assay, the kinetic parameters of PRMT1 with three synthetic peptides
      were determined. An advantage of this assay is the destruction of AdoHcy by
      AdoHcy nucleosidase, which alleviates AdoHcy product feedback inhibition of S
      adenosylmethionine-dependent methyltransferases. Finally, this method may be used
      to assay other enzymes that produce AdoHcy, 5'-methylthioadenosine, or compounds
      that can be cleaved by AdoHcy nucleosidase.

PMID- 16460660
TI  - pFRL7: an ideal vector for eukaryotic promoter analysis.

PMID- 16460661
TI  - A homogeneous time-resolved fluorescence resonance energy transfer assay for IL
      13/IL-13Ralpha1 interaction.

PMID- 16460662
TI  - [Laparoscopic cholecystectomy in a patient with situs inversus].
AB  - Laparoscopic cholecystectomy is the standard approach to manage symptomatic
      gallbladder stones. However, only twelve patients with total situs invertus have
      been previously reported in the literature. We report a new case of a 58-year-old
      patient hospitalized for acute pain of the left hypochondrium with fever. The
      diagnosis of acute cholecystitis with situs inversus totalis was made following
      clinical examination and radiological investigations. Laparoscopic
      cholecystectomy was subsequently performed through a modification of the
      technique to adapt to the mirror image anatomy.

PMID- 16460663
TI  - Integrative analysis of transcript and metabolite profiling data sets to evaluate
      the regulation of biochemical pathways during photomorphogenesis.
AB  - One of the key developmental processes during photomorphogenesis is the
      differentiation of prolamellar bodies of proplastids into thylakoid membranes
      containing the photosynthetic pigment-protein complexes of chloroplasts. To study
      the regulatory events controlling pigment-protein complex assembly, including the
      biosynthesis of metabolic precursors and pigment end products, etiolated
      Arabidopsis thaliana seedlings were irradiated with continuous red light (Rc),
      which led to rapid greening, or continuous far-red light (FRc), which did not
      result in visible greening, and subjected to analysis by oligonucleotide
      microarrays and targeted metabolite profiling. An analysis using BioPathAt, a
      bioinformatic tool that allows the visualization of post-genomic data sets
      directly on biochemical pathway maps, indicated that in Rc-treated seedlings mRNA
      expression and metabolite patterns were tightly correlated (e.g., Calvin cycle,
      biosynthesis of chlorophylls, carotenoids, isoprenoid quinones, thylakoid lipids,
      sterols, and amino acids). K-means clustering revealed that gene expression
      patterns across various biochemical pathways were very similar in Rc- and FRc
      treated seedlings (despite the visible phenotypic differences), whereas a
      principal component analysis of metabolite pools allowed a clear distinction
      between both treatments (in accordance with the visible phenotype). Our results
      illustrate the general importance of integrative approaches to correlate post
      genomic data sets with phenotypic outcomes.

PMID- 16460664
TI  - A comparison between the occluding effects of the Nd:YAG laser and the
      desensitising agent sensodyne on permeation through exposed dentinal tubules of
      endodontically treated teeth: an in vitro study.
AB  - OBJECTIVE: Dentine hypersensitivity may occur due to loss of covering enamel
      and/or loss of cementum after gingival recession, resulting in exposure of
      cervical dentine and patency of dentinal tubules. The effect of thermally cooled
      pulsed neodymium:yttrium-aluminium-garnet (Nd:YAG) laser on the permeability and
      structural appearance of the root canal wall was investigated in vitro. The aim
      of this study was to compare the occluding effect of Nd:YAG laser with that of
      sensodyne on exposed dentine. MATERIAL AND METHODS: Forty freshly extracted human
      maxillary anterior teeth were collected at random. Root canal obturations were
      performed using master apical file no. 60 k-type for obturated teeth. All teeth
      were stored in 100% humidity at 37 degrees C for 48h to allow time for the sealer
      to set. Dentine of 35 teeth was exposed by removing the cementum, and the
      remaining five teeth represented a negative control group. Specimens were
      examined using stereomicroscopy to show the surface topography of the dentine
      substrate before and after treatment with Nd:YAG laser or sensodyne. RESULTS: A
      double-blind technique was used when taking measurements of ink penetration (in
      mm) for each group. Teeth treated by Nd:YAG laser showed the least ink
      penetration, followed by teeth treated by sensodyne. The positive control group
      demonstrated complete ink penetration and the negative control group showed no
      ink penetration. Stereomicroscopic examination of specimens treated with Nd:YAG
      laser showed deposition on the dentinal surface, and specimens treated with
      sensodyne showed partial deposition. Untreated specimens were free of deposition
      and the tubules remained patent. CONCLUSION: There is no significant difference
      in the occluding effect of Nd:YAG laser and sensodyne toothpaste. Both treatments
      have a promising effect on the reduction of permeation through exposed dentinal
      tubules. However, the occluding effect of Nd:YAG laser occurs within seconds
      whereas that of sensodyne takes at least 3 weeks.

PMID- 16460665
TI  - Characterization of Ni transport into brush border membrane vesicles (BBMVs)
      isolated from the kidney of the freshwater rainbow trout (Oncorhynchus mykiss).
AB  - The transport of nickel (Ni) across the renal brush border membrane of the
      rainbow trout was examined in vitro using brush border membrane vesicles (BBMVs).
      Both transmembrane transport of Ni into an osmotically active intravesicular
      space, and binding of Ni to the brush border membrane itself, were confirmed.
      Nickel (Ni) uptake fitted a two component kinetic model. Saturable, temperature
      dependent transport dominated at lower Ni concentrations, with a moderate linear
      diffusive component of Ni transport apparent at higher Ni concentrations. An
      affinity constant (K(m)) for Ni transport within the specifically described
      vesicular media was calculated as 17.9+/-1.9 microM, the maximal rate of
      transport (J(max)) was calculated as 108.3+/-3.7 nmol mg protein(-1) min(-1), and
      the slope of the linear diffusive component was calculated as 0.049+/-0.005 nmol
      mg protein(-1) min(-1) per microM of Ni. Efflux of Ni from BBMVs was fitted to an
      exponential decay curve with a half-time (T(1/2)) of 125.2+/-7.3 s. Ni uptake
      into renal BBMVs was inhibited by magnesium at a 100:1 Mg to Ni molar ratio, and
      by magnesium and calcium at a 1000:1 molar ratio. In the presence of histidine at
      a 100:1 histidine to Ni ratio, Ni uptake was almost completely abolished. At a
      1:1 molar ratio, histidine inhibited Ni uptake by approximately 50%. Ni-histidine
      complexation was rapid, with a T(1/2) of 12.2 s describing the Ni-histidine
      equilibration time needed to inhibit Ni uptake into renal BBMVs by 50%.
      Characterization of Ni transport across cellular membranes is an important step
      in understanding both the processes underlying homeostatic regulation of Ni, and
      the toxicological implications of excessive Ni exposure in aquatic ecosystems.

PMID- 16460666
TI  - Lysophosphatidic acid and lipopolysaccharide bind to the PIP2-binding domain of
      gelsolin.
AB  - The binding of the gelsolin P2 peptide (residues 150-169) with lysophosphatidic
      acid (LPA) and lipopolysaccharide (LPS) was investigated by isothermal titration
      calorimetry. P2 binds to LPS with higher affinity than to LPA. For the
      interaction of 1-oleoyl-LPA with P2 in the absence of salt, K(d) and deltaH
      degrees were 920 nM and -2.07 kcal/mol, respectively, at pH 7.4 and 25 degrees C.
      For the interaction of lipopolysaccharide (LPS) from P. aeruginosa with P2 under
      the same conditions, K(d) was 177 nM and deltaH degrees was -7.6 kcal/mol.

PMID- 16460667
TI  - Treatment motivation, treatment expectancy, and helping alliance as predictors of
      outcome in cognitive behavioral treatment of OCD.
AB  - Predictors of improvement in obsessive-compulsive symptoms (Y-BOCS) in a
      randomized clinical trial with adult obsessive-compulsive disorder outpatients
      were examined. Results of multiple regression analyses revealed that a positive
      helping alliance was significantly predictive of posttreatment Y-BOCS. Treatment
      expectancy and high motivation to change were not significantly related to
      posttreatment outcome. None of the predictors were significantly related to Y
      BOCS levels at 12-month follow-up, but positive alliance showed a trend to
      significance.

PMID- 16460668
TI  - Mechanisms of mindfulness: emotion regulation following a focused breathing
      induction.
AB  - The current study investigated whether a 15 min recorded focused breathing
      induction in a normal, primarily undergraduate population would decrease the
      intensity and negativity of emotional responses to affectively valenced picture
      slides and increase willingness to remain in contact with aversive picture
      slides. The effects of the focused breathing induction were compared with the
      effects of 15 min recorded inductions of unfocused attention and worrying. The
      focused breathing group maintained consistent, moderately positive responses to
      the neutral slides before and after the induction, whereas the unfocused
      attention and worry groups responded significantly more negatively to the neutral
      slides after the induction than before it. The focusing breathing group also
      reported lower negative affect and overall emotional volatility in response to
      the post-induction slides than the worry group, and greater willingness to view
      highly negative slides than the unfocused attention group. The lower-reported
      negative and overall affect in response to the final slide blocks, and greater
      willingness to view optional negative slides by the focused breathing group may
      be viewed as more adaptive responding to negative stimuli. The results are
      discussed as being consistent with emotional regulatory properties of
      mindfulness.

PMID- 16460669
TI  - Contribution of cognitive factors to the prediction of post-traumatic stress
      disorder, phobia and depression after motor vehicle accidents.
AB  - Past research into the psychological consequences of traumatic events has largely
      focused on post-traumatic stress disorder (PTSD), although other anxiety
      disorders and depression are also common in the aftermath of trauma. Little is
      known about differential predictors of these conditions. The present study
      investigated the extent to which theoretically derived cognitive variables
      predict PTSD, phobias and depression after motor vehicle accidents. The cognitive
      predictors were compared to a set of established, mainly non-cognitive
      predictors. In addition, we tested how disorder-specific the cognitive predictors
      are. Participants (n=101) were interviewed within a year after having been
      injured in a motor vehicle accident. Diagnoses of PTSD, travel phobias and
      depression, symptom severities and predictor variables were assessed with self
      report questionnaires and structured interviews. In multiple regression analyses,
      the sets of cognitive variables derived from disorder-specific models explained
      significantly greater proportions of the variance of the symptom severities than
      the established predictors (PTSD 76% vs. 45%, depression 72% vs. 46% and phobia
      66% vs. 40%), and than cognitive variables derived from the models of the other
      disorders. In addition, the majority of individual cognitive variables showed the
      expected pattern of differences between diagnostic groups. The results support
      the hypothesis that disorder-specific sets of cognitive factors contribute to the
      development and maintenance of PTSD, phobias and depression following traumatic
      events.

PMID- 16460670
TI  - Cognitive behavioral therapy for compulsive buying disorder.
AB  - To our knowledge, no psychotherapy treatment studies for compulsive buying have
      been published. The authors conducted a pilot trial comparing the efficacy of a
      group cognitive behavioral intervention designed for the treatment of compulsive
      buying to a waiting list control. Twenty-eight subjects were assigned to receive
      active treatment and 11 to the waiting list control group. The results at the end
      of treatment showed significant advantages for cognitive behavioral therapy (CBT)
      over the waiting list in reductions in the number of compulsive buying episodes
      and time spent buying, as well as scores on the Yale-Brown Obsessive Compulsive
      Scale--Shopping Version and the Compulsive Buying Scale. Improvement was well
      maintained at 6-month follow-up. The pilot data suggests that a cognitive
      behavioral intervention can be quite effective in the treatment of compulsive
      buying disorder. This model requires further testing.

PMID- 16460671
TI  - The acceptability and preference for the psychological treatment of PTSD.
AB  - The acceptability and preference of psychological treatments is important in
      understanding patient treatment seeking, choice, engagement and attrition and
      possibly treatment response in health care. The acceptability of, and preference
      for, 14 different types of psychological treatment for posttraumatic stress
      disorder (PTSD) were investigated in a student population through invitation to
      participate in a web-based survey. Respondents were asked to rate each treatment
      on 10 scales and to rank the treatments in order of preference. Respondents were
      also asked whether they would seek treatment themselves, recommend treatment to
      friends and family, feel stigmatised by suffering from PTSD, had any prior
      knowledge of the treatments and if this had been positive or negative and whether
      they had a history of psychological problems or treatment. A total of 330
      respondents completed the survey. A past or current history of psychological
      problems and treatment was surprisingly high. Almost all respondents indicated
      that they would seek or recommend treatment in spite of high levels of
      stigmatisation. Factor analysis of the 10 scales indicated two factors:
      Endorsement and Discomfort. Rank ordering on preference and Endorsement scores
      was highly consistent. The highly preferred and endorsed treatments involved
      cognitive therapy, exposure or psycho-education in spite of high levels of
      discomfort anticipated with exposure. Treatments involving new technologies, EMDR
      and psychodynamic psychotherapy received the lowest Endorsement and preference.
      There was a modest influence of prior knowledge of a treatment.

PMID- 16460672
TI  - Identification of a novel CoA synthase isoform, which is primarily expressed in
      the brain.
AB  - CoA and its derivatives Acetyl-CoA and Acyl-CoA are important players in cellular
      metabolism and signal transduction. CoA synthase is a bifunctional enzyme which
      mediates the final stages of CoA biosynthesis. In previous studies, we have
      reported molecular cloning, biochemical characterization, and subcellular
      localization of CoA synthase (CoASy). Here, we describe the existence of a novel
      CoA synthase isoform, which is the product of alternative splicing and possesses
      a 29aa extension at the N-terminus. We termed it CoASy beta and originally
      identified CoA synthase, CoASy alpha. The transcript specific for CoASy beta was
      identified by electronic screening and by RT-PCR analysis of various rat tissues.
      The existence of this novel isoform was further confirmed by immunoblot analysis
      with antibodies directed to the N-terminal peptide of CoASy beta. In contrast to
      CoASy alpha, which shows ubiquitous expression, CoASy beta is primarily expressed
      in the brain. Using confocal microscopy, we demonstrated that both isoforms are
      localized on mitochondria. The N-terminal extension does not affect the activity
      of CoA synthase, but possesses a proline-rich sequence which can bring the enzyme
      into complexes with signalling proteins containing SH3 or WW domains. The role of
      this novel isoform in CoA biosynthesis, especially in the brain, requires further
      elucidation.

PMID- 16460673
TI  - The p75(NTR) tumor suppressor induces cell cycle arrest facilitating caspase
      mediated apoptosis in prostate tumor cells.
AB  - The p75 neurotrophin receptor (p75(NTR)) is a death receptor which belongs to the
      tumor necrosis factor receptor super-family of membrane proteins. This study
      shows that p75(NTR) retarded cell cycle progression by induced accumulation of
      cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of
      tumor cells from cell cycle progression by a death domain deleted (DeltaDD)
      dominant-negative antagonist of p75(NTR) showed that the death domain transduced
      anti-proliferative activity in a ligand-independent manner. Conversely, addition
      of NGF ligand rescued retardation of cell cycle progression with commensurate
      changes in components of the cyclin/cdk holoenzyme complex. In the absence of
      ligand, p75(NTR)-dependent cell cycle arrest facilitated an increase in apoptotic
      nuclear fragmentation of the prostate cancer cells. Apoptosis of p75(NTR)
      expressing cells occurred via the intrinsic mitochondrial pathway leading to a
      sequential caspase-9 and -7 cascade. Since the death domain deleted dominant
      negative antagonist of p75(NTR) rescued intrinsic caspase associated apoptosis in
      PC-3 cells, this shows p75(NTR) was integral to ligand independent induction of
      apoptosis. Moreover, the ability of ligand to ameliorate the p75(NTR)-dependent
      intrinsic apoptotic cascade indicates that NGF functioned as a survival factor
      for p75(NTR) expressing prostate cancer cells.

PMID- 16460674
TI  - Simvastatin causes the formation of cholesterol-rich remnants in mice lacking
      apoE.
AB  - Mice that lack apolipoprotein E (apoE) display a severe hypercholesterolemia,
      caused by the accumulation of apolipoprotein B-48 (apoB-48)-carrying remnants of
      chylomicrons and very-low-density lipoproteins in the plasma. Statins are potent
      inhibitors of cholesterol synthesis that, when administered to mice lacking apoE,
      cause paradoxical further increases in plasma cholesterol levels. In the present
      study, we examined the mechanisms responsible for this phenomenon. ApoE-deficient
      mice fed a chow diet containing simvastatin developed, as anticipated, an
      enhanced increase in plasma cholesterol and a decrease in plasma triglycerides.
      Fractionation of the plasma lipoproteins by FPLC revealed that the lipid changes
      were confined to the lipoprotein remnants. Western blot analysis of the remnants
      from the untreated and simvastatin-treated mice showed no differences in their
      apoB-48 content, indicating that both groups of animals accumulated similar
      numbers of remnant particles in the plasma. Following the injection of Triton WR
      1339, the simvastatin-treated mice accumulated in the plasma significantly more
      cholesterol and significantly less triglycerides than the untreated animals.
      These results indicate that the enhanced hypercholesterolemia observed in apoE
      deficient mice treated with simvastatin is not the result of an increased number
      of remnant particles in circulation but is caused by synthesis and secretion into
      the plasma of lipoproteins that are enriched in cholesterol and depleted of
      triglycerides.

PMID- 16460675
TI  - The 2beta2-2beta3 loop of anthrax protective antigen contains a dominant
      neutralizing epitope.
AB  - Anthrax toxin consists of three proteins, protective antigen (PA), lethal factor,
      and edema factor. PA is the major component in the current anthrax vaccine, but
      the antigenic epitopes on it are not well-defined. We generated a pool of toxin
      neutralizing anti-PA monoclonal antibodies (MAbs) to analyze the neutralizing
      epitopes of PA. Nine toxin-neutralizing MAbs obtained were found bound to three
      different domains of PA respectively, among which three MAbs with the strongest
      toxin-neutralizing activity recognized the same epitope within domain 2. This
      epitope was fine mapped to the chymotrypsin-sensitive site, (312)SFFD(315), in
      the 2beta(2)-2beta(3) loop of PA, using phage-displayed random peptide libraries
      and mutation analysis. The result demonstrated for the first time that the
      2beta(2)-2beta(3) loop, which is involved in the transition of PA oligomers from
      prepore to pore, contains a dominant neutralizing epitope. This work contributes
      to the immunological and functional analysis of PA and offers perspective for the
      development of a new epitope vaccine against anthrax.

PMID- 16460676
TI  - Two groups of MYB transcription factors share a motif which enhances trans
      activation activity.
AB  - MYB transcription factors play important roles in many plant developmental
      processes and various defense responses. Two groups of MYB transcription factors
      were found to share a W/Y-MDDIW motif. This motif alone shows no trans-activation
      activity in yeast, however, it enhances the trans-activation activity of the
      neighbor regions greatly. We further show that all the genes in the group 1,
      including the previously reported genes AtMYB21, PsMYB26, AmMYB305, and AmMYB340,
      are predominantly expressed in flowers. Furthermore, we found that these two
      groups of MYB transcription factor genes might be regulated by light, and
      probably preferentially expressed in the darkness, suggesting that they may play
      roles in the light signaling pathway.

PMID- 16460677
TI  - Human adipose tissue-derived mesenchymal stem cells differentiate into insulin,
      somatostatin, and glucagon expressing cells.
AB  - Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a
      pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal
      model. MSC from human bone marrow and adipose tissue represent very similar cell
      populations with comparable phenotypes. Adipose tissue is abundant and easily
      accessible and could thus also harbor cells with the potential to differentiate
      in insulin producing cells. We isolated human adipose tissue-derived MSC from
      four healthy donors. During the proliferation period, the cells expressed the
      stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine
      transcription factor Isl-1. The cells were induced to differentiate into a
      pancreatic endocrine phenotype by defined culture conditions within 3 days. Using
      quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic
      developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together
      with induction of the islet hormones insulin, glucagon, and somatostatin.

PMID- 16460678
TI  - Ligand-independent oligomerization of TLR4 regulated by a short hydrophobic
      region adjacent to the transmembrane domain.
AB  - Toll-like receptors (TLRs) are key receptors for the activation of immune
      responses directed against pathogens. Among the more than 10 identified TLRs,
      TLR4 is the most unique because it associates with a variety of adaptor molecules
      for ligand recognition and signal transduction. However, the relationship between
      the unique characteristics and structural features of TLR4 is poorly defined. In
      this study, we demonstrate a novel biochemical characteristic of TLR4. TLR4, but
      not other TLRs, was observed as highly aggregated forms in immunoblotting.
      Interestingly, substitution of the transmembrane and cytoplasmic domain of TLR4
      with those of other TLRs completely abolished the aggregation of TLR4.
      Furthermore, we found a short hydrophobic region (HR) adjacent to the
      transmembrane domain of TLR4; the TLR4 mutant lacking the HR was not aggregated
      and was nonfunctional in response to lipopolysaccharide. These results suggest
      that the HR may play a critical role in the functional oligomerization of TLR4.

PMID- 16460679
TI  - Effect of moderate UV-B irradiation on Synechocystis PCC 6803 biliproteins.
AB  - In the present study, we investigated the mechanism of UV-B radiation induced
      damage to the light harvesting apparatus of the cyanobacterium Synechocystis
      6803. Liquid chromatography analysis and spectroscopy investigations performed on
      phycobilisomes or isolated biliproteins irradiated with moderate UV-B intensity
      (1.3 W/m(2)) revealed rapid destruction of beta-phycocyanin and a slower damage
      of the other biliproteins, alpha-phycocyanin and both alpha and beta
      allophycocyanin. EPR spin trapping measurements revealed that carbon centered
      adducts of the spin trap DMPO were formed. This evidence indicates that free
      radicals produced from bilins probably attack the polypeptide chain of protein
      inducing its degradation. Our results show that the bilin chromophore is the main
      target of UV-B irradiation, causing structural changes, which in turn induce
      reaction of the chromophore with atmospheric oxygen and lead to production of
      reactive radicals. Our results also demonstrate that beta-phycocyanin is the most
      affected biliprotein, probably due to the presence of two bilins as chromophore.

PMID- 16460680
TI  - Identification of a lysophosphatidylserine receptor on mast cells.
AB  - Lysophosphatidyl-L-serine (lysoPS) is thought to be an immunological regulator
      because it dramatically augments the degranulation of rat peritoneal mast cells
      (RPMCs). This stimulatory effect may be mediated by a lysoPS receptor, but its
      molecule has not been identified yet. During a ligand fishing study for the
      orphan G-protein-coupled receptor 34 (GPR34), we found that lysoPS caused a dose
      dependent inhibition of forskolin-stimulated cAMP accumulation in human GPR34
      expressing Chinese hamster ovary (CHO/hGPR34) cells. The CHO/hGPR34 cells were
      unresponsive to other structurally related phospholipids examined. Quantitative
      real-time-PCR demonstrated that mRNAs of GPR34 are particularly abundant in mast
      cells. The effective lysoPS concentration for RPMC degranulation was similar to
      that required for GPR34 activation, and the structural requirement of lysoPS for
      RPMC degranulation was in good agreement with that observed in CHO/hGPR34 cells.
      These results suggest that GPR34 is the functional mast cell lysoPS receptor.

PMID- 16460682
TI  - Hemorheological abnormalities in lipoprotein lipase deficient mice with severe
      hypertriglyceridemia.
AB  - Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in
      clinical practice. It is known to induce life-threatening acute pancreatitis, but
      its role in atherogenesis remains elusive. Hemorheological abnormality was
      thought to play an important role in pathogenesis of both pancreatitis and
      atherosclerosis. However, hemorheology in severe HTG was not well investigated.
      Recently, we established a severe HTG mouse model deficient in lipoprotein lipase
      (LPL) in which severe HTG was observed to cause a significant increase in plasma
      viscosity. Disturbances of erythrocytes were also documented, including decreased
      deformability, electrophoresis rate, and membrane fluidity, and increased osmotic
      fragility. Scanning electron microscopy demonstrated that most erythrocytes of
      LPL deficient mice deformed with protrusions, irregular appearances or indistinct
      concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol
      (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of
      membrane lipids may be partially responsible for the hemorheological and
      morphologic abnormalities of erythrocytes. This study indicated that severe HTG
      could lead to significant impairment of hemorheology and this model may be useful
      in delineating the role of severe HTG in the pathogenesis of hyperlipidemic
      pancreatitis and atherosclerosis.

PMID- 16460681
TI  - Cross talk of heat shock and heavy metal regulatory pathways.
AB  - Heavy metals induce transcription of human genes including those coding for
      metallothionein and heat shock protein 70 (HSP70). It has been suggested that
      these processes are mediated by metal-activated transcription factors, MTF-1 and
      HSF1, respectively, and are independent of each other. We raised an antibody
      against human MTF-1 which efficiently supershifts the protein-DNA complex formed
      by MTF-1 and its cognate binding sequence, MRE. We discovered that this antibody
      could also supershift complexes formed by HSF1 and its recognition sequence HSE,
      which suggested the involvement of MTF-1 in these complexes. This supershift was
      observed for HSF1/HSE complexes induced by Zn, Cd, Ag, and heat shock.
      Furthermore, overexpression of MTF-1 in HeLa cells markedly reduced metal-induced
      transcription from the hsp70-1 gene promoter which depends on HSF1. These data
      indicate that MTF-1 represses HSF1-mediated transcription probably through a
      direct protein-protein interaction, suggesting a cross talk of two lines of
      stress-responsive regulatory pathways.

PMID- 16460683
TI  - Role of protein kinase C delta in curcumin-induced antioxidant response element
      mediated gene expression in human monocytes.
AB  - The Nrf2/antioxidant response element (ARE) signaling pathway plays a key role in
      activating cellular antioxidants, including heme oxygenase-1 (HO-1), NADPH
      quinone oxidoreductase-1 (NQO1), and glutathione. Protein kinase C (PKC) may also
      regulate these antioxidants, as PKC phosphorylates Nrf2 in vitro. This study
      examined the role of PKC in ARE-mediated gene regulation in human monocytes by
      curcumin, a potent inducer of the Nrf2/ARE pathway. Curcumin increased HO-1 and
      glutamyl cysteine ligase modulator (GCLM) expression and stimulated Nrf2 binding
      to the ARE. Curcumin also rapidly stimulated PKC phosphorylation and Ro-31-8220,
      a pan-PKC inhibitor, decreased curcumin-induced GCLM and HO-1 mRNA expression and
      ARE binding. Rottlerin (a PKC delta inhibitor) and PKC delta antisense
      oligonucleotides significantly inhibited curcumin-induced GCLM and HO-1 mRNA
      expression and ARE binding. Furthermore, a p38 MAP kinase inhibitor reduced GCLM
      and HO-1 expression and rottlerin inhibited curcumin-induced p38 phosphorylation.
      In summary, curcumin activates ARE-mediated gene expression in human monocytes
      via PKC delta, upstream of p38 and Nrf2.

PMID- 16460684
TI  - Alpha-lipoic acid exhibits anti-amyloidogenicity for beta-amyloid fibrils in
      vitro.
AB  - Inhibition of the formation of beta-amyloid fibrils (fAbeta), as well as the
      destabilization of preformed fAbeta in the CNS would be attractive therapeutic
      targets for the treatment of Alzheimer's disease (AD). Using fluorescence
      spectroscopic analysis with thioflavin T and electron microscopic studies, we
      examined the effects of alpha-lipoic acid (LA) and the metabolic product of LA,
      dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of
      fAbeta at pH 7.5 at 37 degrees C in vitro. LA and DHLA dose-dependently inhibited
      fAbeta formation from amyloid beta-protein, as well as their extension. Moreover,
      they destabilized preformed fAbetas. LA and DHLA could be key molecules for the
      development of therapeutics for AD.

PMID- 16460685
TI  - Down-regulation of alpha-synuclein expression can rescue dopaminergic cells from
      cell death in the substantia nigra of Parkinson's disease rat model.
AB  - Fibrillization and aggregation of alpha-synuclein may play a critical role in
      neurodegenerative diseases like Parkinson's diseases. Adeno-associated virus
      (AAV) vector delivery of an alpha-synuclein ribozyme was tested for its silencing
      effect on degenerating nigrostriatal neurons in the MPP(+) model of Parkinson's
      disease. We designed alpha-synuclein ribozyme against human alpha-synuclein gene
      expression and constructed alpha-synuclein ribozymes-carrying rAAV vector
      (designated rAAV-SynRz). Co-transfection of rAAV-SynRz and rAAV-alpha-synuclein
      into HEK293 cells resulted in down-regulation of alpha-synuclein protein
      expression in vitro. Then, rAAV-SynRz was injected into the substantia nigra (SN)
      of MPP(+)-treated rats. Cell counts of TH-positive neurons in the SN revealed
      that rAAV-SynRz significantly protected TH-positive cells against apoptotic
      death, compared with those of rAAV-EGFP or no rAAV injected rats. Our results
      indicate that the use of rAAV-SynRz allowed the survival of higher number of TH
      positive neurons in SN in the MPP(+) model. Down-regulation of alpha-synuclein
      expression could be potentially a suitable target for gene therapy of Parkinson's
      disease.

PMID- 16460686
TI  - Interferon-induced sensitization to apoptosis is associated with repressed
      transcriptional activity of the hTERT promoter in multiple myeloma.
AB  - The aim of the present study was to explore hTERT as a target for IFN-induced
      sensitization to apoptosis in multiple myeloma (MM). IFN-alpha and IFN-gamma
      downregulated telomerase activity in the IL-6-dependent MM cell line U-266-1970.
      In MM cells undergoing IFN-induced sensitization to Fas-mediated apoptosis, the
      repression of telomerase was increased as compared to IFN-alpha treatment alone.
      Similar to the sensitization effect of IFN, the use of a dominant negative
      IkappaBalpha vector inhibiting hTERT activity via transcriptional targeting
      resulted in augmentation of Fas-mediated apoptosis. The mechanism underlying the
      reduction of telomerase activity by IFN was shown to be transcriptional
      repression of the hTERT gene. The present study does not support a direct effect
      of IFN on NF-kappaB binding to the hTERT promoter as underlying the
      transcriptional repression. We conclude that one potential mechanism whereby IFNs
      induce apoptosis sensitization is by repressing hTERT transcription and
      telomerase activity, thereby constituting attractive targets for MM therapy.

PMID- 16460687
TI  - Palmitoylation of LAT contributes to its subcellular localization and stability.
AB  - Palmitoylation is a protein modification for trafficking to lipid raft. Without
      palmitoylation, linker for activation of T cells (LAT), an adaptor molecule
      mediating T cell receptor signaling, is unable to localize in lipid rafts and to
      mediate T cell activation. We here show a novel role for palmitoylation in LAT
      trafficking to the plasma membrane and in the stability of the LAT protein. The
      human LAT mutant lacking palmitoylation was unable to traffic to the plasma
      membrane despite the presence of transmembrane portion. The mouse LAT mutant
      lacking palmitoylation was unstable and susceptible to degradation via the
      proteasome pathway. The human LAT mutant became unstable when the extracellular
      portion was swapped for that from mouse, indicating that both palmitoylation and
      the extracellular portion regulate the stability of LAT. These results suggest
      that palmitoylation has an important role in trafficking to the plasma membrane
      and the stability of LAT.

PMID- 16460688
TI  - Species-specific restriction of cell surface expression of mouse MARCO
      glycoprotein in murine cell lines.
AB  - The MARCO (macrophage receptor with collagenous structure) glycoprotein belongs
      to the scavenger receptor type family of pattern-recognition molecules produced
      by a subset of marginal zone macrophages in the spleen. Stimulation with LPS
      leads to its appearance on macrophages located at other tissue compartments. In
      the present work, we report its in vitro expression by various cell lines using
      transient and stable (lentiviral) gene delivery aimed at investigating the
      signaling properties of this receptor and its analysis using a novel rat
      monoclonal antibody against the SRCR-domain of mouse MARCO. When trying to
      establish stable mouse MARCO-transfectants using lentiviral transduction and
      other methods, we consistently found that MARCO accumulated intracellularly in
      various murine host cells. In contrast, such a phenomenon was not observed in non
      murine cell lines. Our observations indicate the presence of an unexpected
      limitation of the in vitro expression of mouse MARCO glycoprotein in murine cell
      lines. We believe that the failure to express MARCO on the cell surface of the
      many murine cell lines is likely due to the absence of endoplasmic reticulum
      molecular chaperones needed for the correct folding and assembly of the trimeric
      MARCO molecule.

PMID- 16460689
TI  - Some implications of receptor theory for in vivo assessment of agonists,
      antagonists and inverse agonists.
AB  - Drug effects can be classified into three major phenotypes: agonist, antagonist
      and inverse agonist. Agonist and inverse agonist effects are associated with
      receptor activation and inactivation, respectively, whereas antagonism implies
      that a drug produces no effect when administered alone but blocks the effects of
      agonists and inverse agonists. Attention has only recently begun to focus on the
      theoretical and clinical implications of inverse agonists, and studies of inverse
      agonism have also stimulated revisions in receptor theory. This commentary
      addresses two specific issues related to the application of receptor theory to
      studies of inverse agonists in vivo. First, principles of receptor theory suggest
      that increasing drug doses produce a graded pharmacological stimulus that is
      transduced by receptor-containing tissue into a biological response. However,
      assays vary in their ability to detect those responses, and any given assay
      provides only a narrow window on the full range of underlying drug effects.
      Consequently, in vivo assessment of inverse agonists will benefit from
      development of assays sensitive to graded inverse agonist effects. Second,
      detection of inverse agonist effects requires some preexisting level of receptor
      activity (or tone). This tone can result from at least two sources: (a)
      endogenous ligands for the receptor, or (b) constitutive receptor activity.
      Strategies for discriminating these two sources of tone will also contribute to
      the in vivo assessment of inverse agonist effects. Studies with intermediate
      efficacy ligands may be especially helpful in this regard, because their effects
      are differentially influenced by endogenous agonist tone versus constitutive
      receptor tone.

PMID- 16460690
TI  - Functional imaging as a predictor of schizophrenia.
AB  - BACKGROUND: Prospective studies of young individuals at high risk of
      schizophrenia allow the investigation of whether neural abnormalities predate
      development of illness and, if present, have the potential to identify those who
      may become ill. METHODS: We studied young individuals with at least two relatives
      with the disorder. At baseline functional magnetic resonance imaging (fMRI) scan,
      none met criteria for any psychiatric disorder, but four subjects subsequently
      developed schizophrenia. We report the baseline functional imaging findings in
      these subjects performing a sentence completion task compared with normal control
      subjects (n = 21) and those at high risk with (n = 21) and without (n = 41)
      psychotic symptoms who have not developed the disorder. RESULTS: High-risk
      subjects who became ill demonstrated increased activation of the parietal lobe,
      decreased activation of the anterior cingulate, and smaller increases in
      activation with increasing task difficulty in the right lingual gyrus and
      bilateral temporal regions. The hypothesized predictive power of parietal
      activation was supported only in combination with lingual gyrus activity, which
      gave a positive predictive value in this sample of .80. CONCLUSIONS: Although
      these findings should be considered cautiously, as only four subjects who had an
      fMRI scan subsequently became ill, they suggest functional abnormalities are
      present in high-risk subjects who later became ill, which distinguish them not
      only from normal control subjects but also those at high risk who had not
      developed the disorder. These differences are detectable with fMRI and may have
      clinical utility.

PMID- 16460691
TI  - Daytime prazosin reduces psychological distress to trauma specific cues in
      civilian trauma posttraumatic stress disorder.
AB  - BACKGROUND: Persons with posttraumatic stress disorder (PTSD) whose trauma
      related nightmares improve or resolve with bedtime administration of the alpha-1
      adrenergic antagonist prazosin often continue to experience PTSD symptoms during
      the day. This study addressed whether daytime prazosin compared to placebo would
      alleviate psychological distress provoked experimentally by a trauma-related word
      list included in the emotional Stroop (E-Stroop) paradigm. METHODS: Eleven
      persons with civilian trauma PTSD who continued to experience daytime PTSD
      symptoms despite a stable bedtime prazosin dose that suppressed trauma-related
      nightmares were studied. Prazosin and placebo were administered on two different
      occasions in the early afternoon followed two hours later by the E-Stroop.
      Effects of drug on psychological distress were assessed by the Profile of Mood
      States (POMS). RESULTS: POMS total score and an "emotional distress" POMS
      subscale score following trauma-related words were significantly lower in the
      prazosin than placebo condition. There were no treatment effects on E-Stroop
      completion time. In 10 subjects who continued open label daytime prazosin, there
      was a reduction in global PTSD illness severity at 2-week follow-up. CONCLUSIONS:
      Daytime prazosin pretreatment reduced psychological distress specifically to
      trauma cues. Adding daytime prazosin to bedtime prazosin may further reduce
      overall PTSD illness severity and distress.

PMID- 16460692
TI  - Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in
      hippocampal neurogenesis.
AB  - BACKGROUND: Prenatal stress constitutes a developmental risk factor for later
      psychopathology. The behavioral disorders are sustained by neurobiological
      alterations including long-term reduction of hippocampal neurogenesis; its
      deregulation has been involved in cognitive impairments, mood disorders and
      addiction. A major goal is to define periods in development and strategies for
      intervening to prevent the effects of early stressful events. We investigated the
      ability of a postnatal infantile stimulation to prevent prenatal stress-induced
      alteration in hippocampal neurogenesis. METHODS: The influence of postnatal
      handling on prenatal stress-induced changes in hippocampal neurogenesis was
      examined in 4 and 26 month-old male rats. Three distinct phases of the
      neurogenesis were studied: proliferation, survival and neuronal differentiation.
      RESULTS: Prenatal stress reduced hippocampal cell proliferation all throughout
      life. Furthermore, the survival rate of newborn cells, the number of immature
      neurons and the number of differentiated new neurons were reduced in young and
      old prenatally-stressed rats. All those deleterious effects were counteracted by
      neonatal handling. CONCLUSIONS: These data show that finer aspects of brain
      shaping can be rewired by environmental influences occurring at sensitive phase
      of development. They also suggest that infantile stimulation may reverse the
      appearance of behavioral disorders induced by early life stress.

PMID- 16460693
TI  - Antidepressant drug treatment modifies the neural processing of nonconscious
      threat cues.
AB  - BACKGROUND: The amygdala is believed to play a key role in processing emotionally
      salient, threat-relevant, events that require further online processing by
      cortical regions. Emotional disorders such as depression and anxiety have been
      associated with hyperactivity of the amygdala, but it is unknown whether
      antidepressant treatment directly affects amygdala responses to emotionally
      significant information. METHODS: The current study assessed the effects of 7
      days administration of the selective serotonin reuptake inhibitor (SSRI),
      citalopram, on amygdala responses to masked presentations of fearful and happy
      facial expressions in never-depressed volunteers using blood oxygenation level
      dependent (BOLD) functional magnetic resonance imaging. A double-blind, between
      groups design was used with volunteers randomized to 20 mg/day citalopram versus
      placebo. RESULTS: Volunteers receiving citalopram showed decreased amygdala
      responses to masked presentations of threat compared with those receiving
      placebo. Citalopram also reduced responses within the hippocampus and medial
      prefrontal cortex (mPFC) specifically during the fear-relevant stimuli. These
      neural differences were accompanied by decreased recognition of fearful facial
      expressions assessed after the scan. By contrast, there was no effect of
      citalopram on the neural or behavioral response to the happy facial expressions.
      CONCLUSIONS: These results suggest a direct effect of serotonin potentiation on
      amygdala response to threat-relevant stimuli in humans. Such effects may be
      important in the therapeutic actions of antidepressants in depression and
      anxiety.

PMID- 16460695
TI  - Sensorimotor gating deficits in adults with autism.
AB  - BACKGROUND: Prepulse inhibition (PPI) is an operational measure of sensorimotor
      gating and is impaired in a family of neuropsychiatric disorders characterized by
      abnormalities of inhibitory function. Adults with autistic disorder (AD) exhibit
      clinical features of inhibitory deficits, such as restrictive and repetitive
      behaviors, that may be explained by deficits in sensorimotor gating. METHODS:
      Acoustic startle reactivity, habituation, and PPI (30-, 60-, 120-msec
      interstimulus intervals) were assessed in 14 adult men diagnosed with AD and 16
      typically developing normal comparison (NC) participants. All participants were
      administered measures of intelligence and frontal-executive functioning. RESULTS:
      Adults with AD exhibited significantly less PPI in the 60-msec condition than NC
      participants, which was correlated with increased ratings of restricted and
      repetitive behaviors. The groups did not differ on measures of startle amplitude
      or overall habituation. There was, however, a significant group-by-block
      habituation effect. Furthermore, PPI was not related to intelligence but was
      moderately associated with performance on a measure of frontal-executive
      functioning. CONCLUSIONS: Adults with AD have sensorimotor gating deficits
      similar to other neurodevelopmental disorders, implicating a failure of normal
      inhibitory regulation of sensory, motor, and attentional mechanisms. Thus, PPI
      deficits may be indirectly linked to one of the hallmark features of AD.

PMID- 16460694
TI  - Reduction of caudate nucleus volumes in neuroleptic-naive female subjects with
      schizotypal personality disorder.
AB  - BACKGROUND: The caudate nucleus might contribute to the psychopathological and
      cognitive deficits observed in schizotypal personality disorder (SPD), a
      schizophrenia spectrum disorder. Here we focused on female patients, because this
      group is underrepresented in studies of SPD and schizophrenia, and we might learn
      more about the caudate and clinical and cognitive impairments that are unique to
      female patients diagnosed with SPD. METHODS: Magnetic resonance imaging scans,
      obtained on a 1.5-T magnet with 1.5-mm contiguous slices, were used to measure
      the caudate in 32 neuroleptic-naive women with SPD and in 29 female normal
      comparison subjects. Subjects were group-matched for age, parental socioeconomic
      status, and intelligence quotient. RESULTS: We found significantly reduced left
      and right caudate relative volume (8.3%, 7.7%) in female SPD subjects compared
      with normal comparison subjects. In female SPD subjects, we found significant
      correlations between smaller total caudate relative volume and worse performance
      on the Wisconsin Card Sorting test (nonperseverative errors) and on the
      California Verbal Learning Test (verbal memory and learning), and significant
      correlations between smaller total caudate relative volume and both positive and
      negative symptoms on the Structured Interview for Schizotypy. CONCLUSIONS: These
      findings demonstrate that, for female SPD subjects, smaller caudate volume is
      associated with poorer cognitive performance and more schizotypal symptomatology.

PMID- 16460697
TI  - Neural responses to emotional stimuli are associated with childhood family
      stress.
AB  - BACKGROUND: An early family environment marked by harsh parenting has been
      related to risk for multiple mental disorders in adulthood, risks that may be
      mediated, in part, by deficits in emotion regulation skills. This study examined
      neural mechanisms underlying these consequences of "risky" families (RF) by
      exploring neural activity to tasks involving responses to emotional stimuli.
      METHODS: Participants completed an assessment of RF and participated in a
      functional magnetic resonance imaging (fMRI) investigation that examined 1)
      amygdala reactivity to observation of fearful/angry faces; 2) amygdala and right
      ventrolateral prefrontal cortex (RVLPFC) reactivity to labeling emotions
      displayed in these faces; and 3) the relation between RVLPFC and amygdala
      activity during the labeling task. RESULTS: Offspring from nonrisky families
      showed expected amygdala reactivity to observing fearful/angry faces and expected
      activation of RVLPFC while labeling the emotions, which was significantly
      negatively correlated (-.44) with amygdala activation. Offspring from risky
      families showed little amygdala activation during the observation task and a
      strong positive correlation (+.66) between RVLPFC and amygdala activation in the
      labeling task, suggesting a possible dysregulation in the neural systems involved
      in responses to emotional stimuli. CONCLUSIONS: Offspring from risky families
      exhibit atypical responses to emotional stimuli that are evident at the neural
      level.

PMID- 16460696
TI  - Regulation of editing and expression of glutamate alpha-amino-propionic-acid
      (AMPA)/kainate receptors by antidepressant drugs.
AB  - BACKGROUND: Several reports have shown that the glutamatergic system is involved
      in both the pathogenesis of affective and stress-related disorders and in the
      action of antidepressant drugs. In particular, antidepressant treatment was shown
      to modulate expression and function of ionotropic glutamate receptors, to inhibit
      glutamate release and to restore synaptic plasticity impaired by stress. METHODS:
      We analyzed the mRNA expression and RNA editing of alpha-amino-propionic-acid
      (AMPA) and kainate (KA) receptor subunits, in the pre-frontal/frontal cortex
      (P/FC) and hippocampus (HI) of rats chronically treated with three different
      drugs: the selective serotonin (5-HT) reuptake inhibitor fluoxetine, the
      selective noradrenaline (NA) reuptake inhibitor reboxetine and the tricyclic
      antidepressant desipramine. RESULTS: Our data showed that fluoxetine and
      desipramine exerted moderate but selective effects on glutamate receptor
      expression and editing, while reboxetine appeared to be the drug that affects
      glutamate receptors (GluR) most. The most consistent effect, observed with
      pronoradrenergic drugs (desipramine and reboxetine), was a decrease of GluR3
      expression both in P/FC and HI. Interestingly, in HI, the same drugs also
      decreased the editing levels of either the flip (desipramine) or flop
      (reboxetine) form of GluR3. CONCLUSIONS: Overall, these results point to specific
      and regionally discrete changes in the expression and editing level of glutamate
      receptors and, in particular, to a selective reduction of conductance for GluR3
      containing receptors following treatment with antidepressant drugs. These data
      support the hypothesis that changes in glutamate neurotransmission are involved
      in the therapeutic effects induced by these drugs.

PMID- 16460698
TI  - Somal size of immunolabeled pyramidal cells in the prefrontal cortex of subjects
      with schizophrenia.
AB  - BACKGROUND: Although the somal volume of Nissl-stained deep layer 3 pyramidal
      cells is reduced in prefrontal cortex area 9 of subjects with schizophrenia, the
      subset of large pyramidal cells immunoreactive (IR) for nonphosphorylated
      neurofilament protein (NNFP) is not. Consequently, we hypothesized that the somal
      volume of another subset of pyramidal cells immunoreactive for neuronal calcium
      binding protein-1 (Necab-1) is significantly reduced in schizophrenia. METHODS:
      We labeled Necab-1-IR pyramidal neurons using immunoperoxidase techniques and
      estimated the mean somal volume in deep layer 3 of area 9 in 13 matched pairs of
      control and schizophrenic subjects. Identical studies were conducted for
      pyramidal neurons immunoreactive for neuronal nuclear protein (Neu-N), which is
      present in all neurons. RESULTS: In subjects with schizophrenia, neither the mean
      somal volume of Necab-1-IR pyramidal neurons nor of Neu-N-IR pyramidal neurons
      was significantly different from control subjects. In addition, the mean somal
      volume of Neu-N-IR cells was larger than that of Nissl-stained cells in both
      subject groups, and the magnitude of this difference was greater for the subjects
      with schizophrenia. CONCLUSIONS: These findings suggest that immunoperoxidase
      techniques are associated with an overestimation of the volume of labeled
      neurons. This confound appears to interact with disease state, and thus obscures
      differences between diagnostic groups.

PMID- 16460699
TI  - A review of serotonin toxicity data: implications for the mechanisms of
      antidepressant drug action.
AB  - Data now exist from which an accurate definition for serotonin toxicity (ST), or
      serotonin syndrome, has been developed; this has also lead to precise, validated
      decision rules for diagnosis. The spectrum concept formulates ST as a continuum
      of serotonergic effects, mediated by the degree of elevation of intrasynaptic
      serotonin. This progresses from side effects through to toxicity; the concept
      emphasizes that it is a form of poisoning, not an idiosyncratic reaction.
      Observations of the degree of ST precipitated by overdoses of different classes
      of drugs can elucidate mechanisms and potency of drug actions. There is now
      sufficient pharmacological data on some drugs to enable a prediction of which
      ones will be at risk of precipitating ST, either by themselves or in combinations
      with other drugs. This indicates that some antidepressant drugs, presently
      thought to have serotonergic effects in animals, do not exhibit such effects in
      humans. Mirtazapine is unable to precipitate serotonin toxicity in overdose or to
      cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and
      moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic
      antidepressants (other than clomipramine and imipramine) do not precipitate
      serotonin toxicity and might not elevate serotonin or have a dual action, as has
      been assumed.

PMID- 16460700
TI  - Neural anomalies during sustained attention in first-degree biological relatives
      of schizophrenia patients.
AB  - BACKGROUND: A deficit in sustained attention might serve as an endophenotype for
      schizophrenia and therefore be a useful tool in understanding the genetic
      underpinnings of the disorder. We sought to detail functional brain abnormalities
      associated with sustained attention (i.e., vigilance) in individuals with genetic
      liability for schizophrenia. METHODS: We gathered electrophysiological data from
      23 schizophrenia patients, 28 first-degree biological relatives of schizophrenia
      patients, and 23 nonpsychiatric control subjects while they performed a degraded
      stimulus continuous performance task. Inclusion of sensory control trials allowed
      separation of target detection and vigilance effects on brain potentials.
      RESULTS: Schizophrenia patients, but not relatives, showed a behavioral deficit
      in sustained attention. During target detection, relatives exhibited diminished
      late positive amplitudes (P3b, i.e., P300) over parietal brain regions and
      augmented early posterior (P1) and right frontal (anterior N1) potentials.
      Electrophysiological anomalies were still evident after the exclusion of three
      relatives with histories of psychosis. CONCLUSIONS: Genetic liability for
      schizophrenia is associated with augmented early and diminished late brain
      potentials during sustained attention. Electrophysiological anomalies suggestive
      of right frontal-posterior parietal dysfunction might represent neural expression
      of genetic liability for schizophrenia. Electrophysiological indices also seem to
      be more sensitive than behavioral measures in assessing genetic liability for
      schizophrenia.

PMID- 16460701
TI  - Mapping corpus callosum deficits in autism: an index of aberrant cortical
      connectivity.
AB  - BACKGROUND: Volumetric studies have reported reductions in the size of the corpus
      callosum (CC) in autism, but the callosal regions contributing to this deficit
      have differed among studies. In this study, a computational method was used to
      detect and map the spatial pattern of CC abnormalities in male patients with
      autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26
      control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging
      (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using
      traditional morphometric methods. Three-dimensional (3D) surface models of the CC
      were also created from the MRI scans. Statistical maps were created to visualize
      morphologic variability of the CC and to localize regions of callosal thinning in
      autism. RESULTS: Traditional morphometric methods detected a significant
      reduction in the total callosal area and in the anterior third of the CC in
      patients with autism; however, 3D maps revealed significant reductions in both
      the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the
      CC revealed callosal deficits in autism with greater precision than traditional
      morphometric methods. These abnormalities suggest aberrant connections between
      cortical regions, which is consistent with the hypothesis of abnormal cortical
      connectivity in autism.

PMID- 16460702
TI  - Extensive spatial training does not negate age differences in response latency.
AB  - Previously, Nippak et al. [Nippak, P.M.D., Chan, A.D.F., Campbell, Z.,
      Muggenburg, B., Head, E., Ikeda-Douglas, C., Murphy, H., Cotman, C.W., Milgram,
      N.W., 2003. Response latency in the canine: mental ability or mental strategy?
      Behav. Neurosci. 117 (5), 1066-1075] reported that young dogs respond
      significantly slower than aged dogs during the acquisition of a three-component
      delayed non-match to position (3-DNMP) task. Thus, we examined how age influences
      response latency (RL) when animals are trained extensively on the 3-DNMP task.
      Animals were separated into two groups based on their task sophistication. The
      first group comprised young (N=5) and aged (N=10) dogs that received extensive
      spatial training on a two-component delayed non-match to position task (2-DNMP)
      before 3-DNMP testing, while the second group of young (N=8) and aged (N=11)
      animals received extensive training on a variety of other non-spatial cognitive
      tasks between each 3-DNMP test period. RL age differences were absent following
      extensive 3-DNMP testing; however, other age-dependent performance differences
      emerged: all young animals learned the task and displayed RL slowing and superior
      response accuracy (RA) on the center-incorrect (CI) subtest, while several aged
      animals failed to learn the task and displayed no RL or RA subtest variations
      even when they acquired the task. Toates's [Toates, F., 1998. The interaction of
      cognitive and stimulus-response processes in the control of behaviour, Neurosci.
      Biobehav. Rev. 22 (1), 59-83] theory of RL and mental strategy was proposed to
      explain these age differences in response strategies: the fast-responding aged
      animals utilized stimulus-response strategies, while the slow-responding young
      animals adopted cognitive strategies, a specific requirement for solving the CI
      subtest.

PMID- 16460704
TI  - Training in Morse code enhances involuntary attentional switching to acoustic
      frequency: Evidence from ERPs.
AB  - This study examined the possibility that learning Morse code could result in
      cortical changes in processing of physical acoustic features, as indexed by the
      mismatch negativity (MMN) and P3a components of the auditory event-related
      potential (ERP). ERPs were recorded in 9 subjects who were learning Morse code.
      The subjects were presented with auditory stimuli at 3 different times relative
      to their training (before, during and after). These stimuli were presented within
      an auditory 'oddball' paradigm, with repetitive standard stimuli interspersed by
      one of three infrequent deviant stimuli (duration, frequency or SOA). The data
      showed that there was a significant increase in the P3a only for frequency
      deviants as a function of training, whereas the MMN response was not affected by
      the training. These data are interpreted in terms of an attentional switching to
      unfamiliar changes that participants would not expect among the signals that they
      would grow to anticipate while receiving Morse code.

PMID- 16460706
TI  - Frontal positivity discriminates true from false recognition.
AB  - Lesion studies have indicated a presumably recollection-based involvement of the
      prefrontal cortex in the discrimination of true and false recognition. ERP
      studies of word list recognition, on the other hand, generally did not yield such
      effects in the time range associated with recollection processes which might
      relate to variables like study-test shifts of context. The present study aimed to
      further explore ERP correlates of true and false recognition, using an
      experimental procedure which emphasized recollection of item-specific
      information. Young healthy subjects performed a word recognition task, in which
      items previously presented (targets), semantically related distractors (lures),
      and unrelated new items (distractors) had to be classified as old or new followed
      by a remember/know judgment for old items. Items were presented visually during
      both study and test. Correct old responses to targets elicited significantly more
      pronounced positive waveforms in comparison to correct rejections of distractors
      (old/new effect) between 400 and 700 ms after stimulus onset at all left and
      central electrode positions. A significant old/new effect for false alarms to
      lures was observed only at the left parietal electrode. ERPs associated with hits
      and false alarms to lures were similar at parietal but differed at frontal
      electrode positions. This pattern of results suggests a differential processing
      of true and false recognition in frontal and posterior brain regions when item
      specific recollection is facilitated. Our findings support the assumption of
      monitoring processes in parallel to the recollection of item-specific information
      in recognition memory, which might become affected by illusory sensory
      information generated by posterior areas.

PMID- 16460703
TI  - Neurophysiological evidence for context-dependent encoding of sensory input in
      human auditory cortex.
AB  - Attention biases the way in which sound information is stored in auditory memory.
      Little is known, however, about the contribution of stimulus-driven processes in
      forming and storing coherent sound events. An electrophysiological index of
      cortical auditory change detection (mismatch negativity [MMN]) was used to assess
      whether sensory memory representations could be biased toward one organization
      over another (one or two auditory streams) without attentional control. Results
      revealed that sound representations held in sensory memory biased the
      organization of subsequent auditory input. The results demonstrate that context
      dependent sound representations modulate stimulus-dependent neural encoding at
      early stages of auditory cortical processing.

PMID- 16460705
TI  - Selective attention to human voice enhances brain activity bilaterally in the
      superior temporal sulcus.
AB  - Regional cerebral blood flow was measured with positron emission tomography (PET)
      in 10 healthy male volunteers. They heard two binaurally delivered concurrent
      stories, one spoken by a male voice and the other by a female voice. A third
      story was presented at the same time as a text running on a screen. The subjects
      were instructed to attend silently to one of the stories at a time. In an
      additional resting condition, no stories were delivered. PET data showed that in
      comparison with the reading condition, the brain activity in the speech-listening
      conditions was enhanced bilaterally in the anterior superior temporal sulcus
      including cortical areas that have been reported to be specifically sensitive to
      human voice. Previous studies on attention to non-linguistic sounds and visual
      objects, in turn, showed prefrontal activations that are presumably related to
      attentional control functions. However, comparisons of the present speech
      listening and reading conditions with each other or with the resting condition
      indicated no prefrontal activity, except for an activation in the inferior
      frontal cortex that was presumably associated with semantic and syntactic
      processing of the attended story. Thus, speech listening, as well as reading,
      even in a distracting environment appears to depend less on the prefrontal
      control functions than do other types of attention-demanding tasks, probably
      because selective attention to speech and written text are over-learned actions
      rehearsed daily.

PMID- 16460707
TI  - Release of GABA from sensory neurons transduced with a GAD67-expressing vector
      occurs by non-vesicular mechanisms.
AB  - We have demonstrated that dorsal root ganglion neurons transduced with a
      recombinant replication-defective herpes simplex virus vector coding for glutamic
      acid decarboxylase (QHGAD67) release GABA to produce an analgesic effect in
      rodent models of pain. In this study, we examined the mechanism of transgene
      mediated GABA release from dorsal root ganglion neurons in vitro and in vivo.
      Release of GABA from dorsal root ganglion neurons transduced with QHGAD67 was not
      increased by membrane depolarization induced by 60 mM extracellular K+ nor
      reduced by the removal of Ca2+ from the medium. Release of GABA from transduced
      dorsal root ganglion neurons was, however, blocked in a dose-dependent manner by
      NO-711, a selective inhibitor of the GABA transporter-1. The amount of GABA
      released from a spinal cord slice preparation, prepared from animals transduced
      by subcutaneous inoculation of QHGAD67 in the hind paws, was substantially
      increased compared to animals transduced with control vector Q0ZHG or normal
      animals, but the amount of GABA released was not changed by stimulation of the
      dorsal roots at either low (0.1 mA, 0.5-ms duration) or high (10 mA, 0.5-ms
      duration) intensity. We conclude that QHGAD67-mediated GABA release from dorsal
      root ganglion neurons is non-vesicular, independent of electrical depolarization,
      and that this efflux is mediated through reversal of the GABA transporter.

PMID- 16460708
TI  - Selective serotonin depletion does not regulate hippocampal neurogenesis in the
      adult rat brain: differential effects of p-chlorophenylalanine and 5,7
      dihydroxytryptamine.
AB  - Serotonin is suggested to regulate adult hippocampal neurogenesis, and previous
      studies with serotonin depletion reported either a decrease or no change in adult
      hippocampal progenitor proliferation. We have addressed the effects of serotonin
      depletion on distinct aspects of adult hippocampal neurogenesis, namely the
      proliferation, survival and terminal differentiation of hippocampal progenitors.
      We used the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA) or the
      serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to deplete serotonin
      levels. 5,7-DHT selectively decreased hippocampal serotonin levels, while PCPA
      resulted in a significant decline in both serotonin and norepinephrine levels. We
      observed a robust decline in the proliferation and survival of adult hippocampal
      progenitors following PCPA treatment. This was supported by a decrease in the
      number of doublecortin-positive cells in the neurogenic niche in the hippocampus.
      In striking contrast, 5,7-DHT did not alter the proliferation or survival of
      adult hippocampal progenitors and did not alter the number of doublecortin
      positive cells. The terminal differentiation of adult hippocampal progenitors was
      not altered by either PCPA or 5,7-DHT treatment. An acute increase in serotonin
      levels also did not influence adult hippocampal progenitor proliferation. These
      results suggest that selective serotonin depletion or an acute induction in
      serotonin levels does not regulate adult hippocampal neurogenesis, whereas
      treatment with PCPA that induces a decline in both serotonin and norepinephrine
      levels results in a significant decrease in adult hippocampal neurogenesis. Our
      results highlight the need for future studies to examine the role of other
      monoamines in both the effects of stress and antidepressants on adult hippocampal
      neurogenesis.

PMID- 16460709
TI  - Microarray analysis of gene expression patterns in adult spinal motoneurons after
      different types of axonal injuries.
AB  - Three experimental models of axonal injuries in adult rat spinal motoneurons were
      established to investigate changes of gene expression in response to such
      injuries. We took advantage of cDNA microarray analysis to determine the
      differential expression of genes in injured motoneurons following distal axotomy
      or root avulsion in the absence or presence of BDNF. The major finding was that,
      in response to proximal axonal injury (avulsion), expression of genes that are
      known to facilitate neuronal survival and axonal regeneration (e.g., IGFRII,
      PI3K, IGFBP-6, GSTs, GalR2) were down-regulated; but following treatment with
      BDNF they were up-regulated. In addition, the expression of genes known to be
      involved in apoptosis and DNA damage (e.g., ANX5, TS, ALR) were down-regulated in
      BDNF-treated animals with avulsion. Furthermore, many functional families of
      genes previously shown to play roles in the pathophysiology of axonal injury,
      including SNAP-25A, SV2B, Ras-related ras3a/4b, ERK1/2, 14-3-3 proteins,
      proteasome proteins, oncogenes, GAP-43, and NMDAR1, were altered after either
      distal axotomy or avulsion injury. Some of the changes in gene expression,
      including Lim-2, FRAG1, GlaR2, GSTs, ALR, TS, ANX3/5, and nhe1/2, are first
      reported here in injured motoneurons. The differential expression of genes
      identified by the expression arrays was confirmed by gene-specific RT-PCR for
      eight genes (GAP-43, IGFR II, Lim-2, MIF, NDAP1, TS, PCC3, and FRAG1) and by in
      situ hybridization for Lim-2. These results suggest that abnormal regulation of
      particular biochemical pathways may induce motoneuron death after ventral root
      avulsion in adult animals. This study presents an approach for selecting specific
      genes and their products that may be involved in motoneuron degeneration
      following axonal injuries.

PMID- 16460710
TI  - Prefrontal cortex D1 modulation of the reinforcing properties of cocaine.
AB  - The involvement of the dopaminergic pathway from the ventral tegmental area (VTA)
      to the nucleus accumbens (NAcc) in the reinforcing properties of many drugs of
      abuse is well established. Though the prefrontal cortex (PFC) exhibits
      significant influence over activity in this pathway, its role in drug abuse is
      less defined. The present experiment investigated the impact of PFC D1 activity
      on cocaine self-administration (0.25, 0.75 mg/kg/inj) under progressive (PR) and
      fixed ratio (FR) schedules of reinforcement by assessing immediate and delayed
      effects of bilateral intra-PFC infusions of a D1 agonist (SKF 38393; 0.23
      microg/side) and antagonist (SCH 23390; 0.25 microg/side). Immediately following
      infusion of dopaminergic agents or vehicle, no significant changes in self
      administration occurred under any tested condition. However, 24 h after intra-PFC
      antagonist treatment, significantly lower PR breakpoints were observed for low
      (0.25 mg/kg), but not moderate (0.75 mg/kg) unit doses of self-administered
      cocaine. Locomotor activity levels during these assessments were unaffected by
      intra-PFC treatments. On an FR-3 schedule of reinforcement, the 0.25 cocaine unit
      dose elicited higher total cocaine intake and hyperlocomotor activation during a
      shorter session, but intra-PFC treatment had no significant effects on the number
      of reinforced responses or behavioral activity. The observation of decreased
      cocaine breakpoints after intra-PFC DA antagonist treatment reflects decrements
      in cocaine reinforcement efficacy. This finding corresponds temporally with
      previous work showing increased NAcc DA levels after similar treatment. Current
      findings demonstrate that transient changes in PFC DA neurotransmission can
      specifically influence reinforced behaviors without affecting overall behavioral
      activation.

PMID- 16460711
TI  - Calcium channel alpha2-delta type 1 subunit is the major binding protein for
      pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo
      autoradiographic study in alpha2-delta type 1 genetically modified mice.
AB  - Pregabalin is a synthetic amino acid compound effective in clinical trials for
      the treatment of post-herpetic neuralgia, diabetic peripheral neuropathy,
      generalized anxiety disorder and adjunctive therapy for partial seizures of
      epilepsy. However, the mechanisms by which pregabalin exerts its therapeutic
      effects are not yet completely understood. In vitro studies have shown that
      pregabalin binds with high affinity to the alpha(2)-delta (alpha(2)-delta)
      subunits (Type 1 and 2) of voltage-gated calcium channels. To assess whether
      alpha(2)-delta Type 1 is the major central nervous system (CNS) binding protein
      for pregabalin in vivo, a mutant mouse with an arginine-to-alanine mutation at
      amino acid 217 of the alpha(2)-delta Type 1 protein (R217A mutation) was
      generated. Previous site-directed mutagenesis studies revealed that the R217A
      mutation dramatically reduces alpha(2)-delta 1 binding to pregabalin in vitro. In
      this autoradiographic analysis of R217A mice, we show that the mutation to
      alpha(2)-delta Type 1 substantially reduces specific pregabalin binding in CNS
      regions that are known to preferentially express the alpha(2)-delta Type 1
      protein, notably the neocortex, hippocampus, basolateral amygdala and spinal
      cord. In mutant mice, pregabalin binding was robust throughout regions where the
      alpha(2)-delta Type 2 subunit mRNA is abundant, such as cerebellum. These
      findings, in conjunction with prior in vitro binding data, provide evidence that
      the alpha(2)-delta Type 1 subunit of voltage-gated calcium channels is the major
      binding protein for pregabalin in CNS. Moreover, the distinct localization of
      alpha(2)-delta Type 1 and mutation-resistant binding (assumed to be alpha(2)
      delta Type 2) in brain areas subserving different functions suggests that
      identification of subunit-specific ligands could further enhance pharmacologic
      specificity.

PMID- 16460712
TI  - Endomorphin-2 in the medial NTS attenuates the responses to baroreflex
      activation.
AB  - We have previously reported that microinjections of endomorphin-2 (E-2; an
      endogenous mu-receptor agonist) into the medial subnucleus of the NTS (mNTS)
      elicit depressor and bradycardic responses via activation of ionotropic glutamate
      receptors located on secondary mNTS-neurons. Based on this report, it was
      hypothesized that activation of secondary mNTS neurons by E-2 may result in an
      exaggeration of baroreflex responses. In order to test this hypothesis,
      baroreflex responses were studied in adult, urethane-anesthetized, artificially
      ventilated, male Wistar rats before and after the microinjections of E-2 into the
      mNTS. Baroreceptors were stimulated by applying pressure increments (80-100 mm
      Hg) in the carotid sinus and by electrical stimulation (stimulus intensity: 0.5
      V, frequencies 5, 10, and 25 pulses/s, pulse duration: 1 ms) of the aortic nerve
      for 30-s periods. Baroreceptor stimulation elicited depressor and bradycardic
      responses. Microinjections (100 nl) of E-2 (0.4 mmol/l) into the mNTS attenuated
      the baroreflex responses. Microinjections of naloxone (an opioid receptor
      antagonist) into the mNTS (0.5 mmol/l) did not alter baroreflex responses. Based
      on these results, it was concluded that activation of mu-opioid receptors in the
      mNTS attenuates baroreflex responses. Possible mechanisms for excitatory effects
      of E-2 in the mNTS resulting in depressor and bradycardic responses, on one hand,
      and inhibitory effects resulting in attenuation of baroreflex responses, on the
      other, are discussed.

PMID- 16460713
TI  - Novel non-uniform distribution of serotonin transporter in the mouse hippocampus
      and neocortex revealed by N- and C-terminal domain-specific immunohistochemistry.
AB  - Serotonergic fibers have a general feature of extending diffusely throughout the
      brain and appear to innervate broad areas rather uniformly. The present study
      revealed marked regional difference in their immunoreactivities against serotonin
      transporter by using two antibodies that recognize either N- or C-terminal domain
      of the transporter. C-terminal-specific labeling was ubiquitous, whereas N
      terminal-specific labeling was confined to hippocampal CA1 region, somatosensory
      cortex, and other areas, suggesting novel non-uniformity in the serotonergic
      system.

PMID- 16460714
TI  - Increased nitric oxide caused by the ketogenic diet reduces the onset time of
      kainic acid-induced seizures in ICR mice.
AB  - Although the antiepileptic effects of the ketogenic diet (KD) are well
      documented, the mechanisms underlying this action remain obscure. Nitric oxide
      (NO) has long been thought to play a role in regulating seizures. However, the
      effects of the KD on endogenous NO production have not been characterized.
      Therefore, the present study was designed to examine the effect of the KD on
      endogenous NO production, as well as the precise role of NO in kainic acid (KA)
      induced seizures, in male ICR mice. We first found that preadministration of the
      KD for 4 weeks increased endogenous NO generation in the hippocampus. We also
      demonstrated that the increase in NO induced by the KD resulted from increased
      neuronal NO synthase (nNOS) activity and exerted an antiepileptic effect on KA
      induced seizures, based on the results of experiments using NOS-knockout mice and
      two NOS inhibitors, N-omega-nitro-L-arginine methyl ester (L-NAME) and 7
      nitroindazole (7-NI). These data suggest that the antiepileptic effects of the KD
      might be mediated, at least in part, by increased NO levels in the hippocampus.

PMID- 16460715
TI  - The power of simulation: imagining one's own and other's behavior.
AB  - A large number of cognitive neuroscience studies point to the similarities in the
      neural circuits activated during the generation, imagination, as well as
      observation of one's own and other's behavior. Such findings support the shared
      representations account of social cognition, which is suggested to provide the
      basic mechanism for social interaction. Mental simulation may also be a
      representational tool to understand the self and others. However, successfully
      navigating these shared representations--both within oneself and between
      individuals--constitutes an essential functional property of any autonomous
      agent. It will be argued that self-awareness and agency, mediated by the
      temporoparietal (TPJ) area and the prefrontal cortex, are critical aspects of the
      social mind. Thus, differences as well as similarities between self and other
      representations at the neural level may be related to the degrees of self
      awareness and agency. Overall, these data support the view that social cognition
      draws on both domain-general mechanisms and domain-specific embodied
      representations.

PMID- 16460716
TI  - Improved selective and divided spatial attention in early blind subjects.
AB  - Spatial attention paradigms using auditory or tactile stimulation were used to
      explore neural and behavioral reorganization in early blind subjects. Although it
      is commonly assumed that blind subjects outperform sighted subjects in such
      tasks, the empirical data to confirm this remain controversial. Moreover,
      previous studies have often confounded factors of sensory acuity with those of
      attention. In the present work, we compared the performance of individually
      matched early blind and sighted subjects during auditory and tactile tasks. These
      consisted of sensory acuity tests, simple reaction time task as well as selective
      and divided spatial attention tasks. Based on sensory measurements, we made sure
      that the reliability and salience of auditory and tactile information were
      identical between the two populations to estimate attentional performance
      independently of sensory influence. Results showed no difference between groups
      in either sensory sensitivity or simple reaction time task for both modalities.
      However, blind subjects displayed shorter reaction times than sighted subjects in
      both tactile and auditory selective spatial attention tasks and also in bimodal
      divided spatial attention tasks. The present study thus demonstrates an enhanced
      attentional performance in early blind subjects which is independent of sensory
      influence. These supra-normal abilities could be related to quantitative and
      qualitative changes in the way early visually deprived subjects process non
      visual spatial information.

PMID- 16460717
TI  - Determination of the degree of acetylation of chitosan by UV spectrophotometry
      using dual standards.
AB  - Determination of the degree of acetylation of chitosan by UV spectrophotometry
      using dual standards is investigated. The UV absorbance of a pure chitosan
      solution is contributed additively by the N-acetylglucosamine and glucosamine
      residues; the absorbance divided by the total molar concentration of the residues
      (A/c(t)) is linearly related to the degree of acetylation (DA). Using acetyl
      glucosamine and glucosamine hydrochloride as standards in 0.1M hydrochloric acid
      solution, the equation obtained by linear regression is A/c(t)=3.3615 DA+0.0218,
      R(2)=0.9958. The DA of the analytical sample (m milligram of chitosan in V liters
      solution) can be calculated by.

PMID- 16460718
TI  - A novel nonsense mutation in the LPL gene in a Chinese neonate with
      hypertriglyceridemia.
AB  - BACKGROUND: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive
      disorder characterized by hypertriglyceridemia. The genetic defect lies in a
      mutation of the LPL gene. METHODS: A Chinese neonate with non-consanguineous
      parents was incidentally found to have hypertriglyceridemia. Mutation in her LPL
      gene was screened by using polymerase chain reaction and direct DNA sequencing.
      RESULTS: Homozygous missense mutations (L252V) were detected in the LPL gene of
      the patient. A novel nonsense mutation (C27X) was also identified. CONCLUSION:
      Our finding supports L252V mutation in the LPL gene is a common mutation in
      Chinese with familial hyperchylomicronemia syndrome. DNA-based diagnosis in this
      syndrome is definitive. It saves the need for heparin-infusion test, which
      carries the risk of hemorrhage, and the measurement of LPL activity, which is
      tedious and is not widely available.

PMID- 16460719
TI  - Vitronectin in atherosclerotic disease.
AB  - Atherosclerosis is characterized by the development of an intimal thickening that
      contains monocytes, T lymphocytes, and smooth muscle cells within an accumulation
      of lipid and extracellular matrix proteins. Vitronectin is a plasma glycoprotein
      implicated as a regulator of diverse physiological process, including blood
      coagulation, fibrinolysis, pericellular proteolysis, complement dependent immune
      responses, and cell attachment and spreading. Because of its ability to bind
      platelet glycoproteins and mediate platelet adhesion and aggregation at sites of
      vascular injury, vitronectin has become an important mediator in the pathogenesis
      of coronary atherosclerosis.

PMID- 16460720
TI  - Metabolomic and bioinformatic analyses in asphyxiated neonates.
AB  - OBJECTIVES: We tested the application of bioinformatic algorithms in studying the
      metabolomic profiles of neonatal urine samples with clinical evidence of severe
      asphyxia at birth and subsequent neurodevelopmental handicap. DESIGN AND METHODS:
      The clinical outcomes of 256 newborns that required direct admission to neonatal
      intensive care unit for respiratory support or did not require direct admission
      were studied. Urinary metabolite profiles were measured by high throughput mass
      spectrometry and analyzed by bioinformatic methods. RESULTS: We found a positive
      relationship between suppressed biochemical networks involved in macromolecular
      synthesis and birth asphyxia associated with significant neonatal oxidative
      stress and morbidity. The metabolomic discriminators between good neonatal
      outcome and poor neonatal outcome were established using hierarchical clustering
      analysis. Concentrations of eight urinary organic acids in distinct biochemical
      pathways were elevated and significantly associated with the prognosis of
      neurodevelopmental handicap with high sensitivity and specificity: ethylmalonate,
      3-hydroxy-3-methylglutarate, 2-hydroxy-glutarate and 2-oxo-glutarate were
      associated with good neonatal outcome, whereas glutarate, methylmalonate, 3
      hydroxy-butyrate and orotate were associated with poor outcome. CONCLUSIONS: The
      data demonstrated the potential application of bioinformatics methods in this
      metabolomic study and proved its clinical relevance.

PMID- 16460721
TI  - Rapid measurement of S-100B serum protein levels by Elecsys S100 immunoassay in
      patients undergoing carotid artery stenting or endarterectomy.
AB  - OBJECTIVES: This study was designed to apply the rapid Elecsys S100 immunoassay
      for real-time measurement of S100 protein serum levels indicating acute brain
      damage in patients undergoing carotid artery stenting (CAS) or endarterectomy
      (CEA). DESIGN AND METHODS: Data of 14 CAS patients were compared to those of 43
      CEA and 14 control patients undergoing coronary angiography (CA). S100 serum
      levels were measured by the full-automatic Elecsys S100 immunoassay and compared
      to those obtained by the well-established LIA-mat S100 system. RESULTS: In
      contrast to CAS and CA patients, median S100 serum levels of CEA patients
      significantly increased to 0.24 ng/mL before declamping, but subsequently
      returned to baseline. Three CEA patients with neurological deficits showed
      sustained elevated S100 levels 6 h after extubation. Absolute S100 values were
      not significantly different between the two methods. Bland-Altman plot analyses
      displayed a good agreement, mostly indicating slightly smaller values applying
      the Elecsys S100 system. CONCLUSIONS: The Elecsys S100 system appears to be
      suitable for rapid real-time detection of neurological deficits in patients
      undergoing CAS and CEA. Persistent elevations of Elecsys S100 levels during CEA
      were associated with prolonged neurological disorders, whereas transient
      increases seem to represent impaired blood-brain barrier integrity without
      neurological deficits.

PMID- 16460722
TI  - Color naming universals: the case of Berinmo.
AB  - Proponents of a self-identified 'relativist' view of cross-language color naming
      have confounded two questions: (1) Is color naming largely subject to local
      linguistic convention? and (2) Are cross-language color naming differences
      reflected in comparable differences in color cognition by their speakers? The
      'relativist' position holds that the correct answer to both questions is Yes,
      based on data from the Berinmo language of Papua New Guinea. It is shown here
      that the Berinmo facts instead support a more complex view -- that cross-language
      color naming follows non-trivial universal tendencies, while cross-language color
      naming differences do indeed correlate with differences in color cognition. The
      rhetoric of 'relativity' versus 'universalism' impedes understanding of cross
      language color naming and cognition.

PMID- 16460723
TI  - Oncopeltus fasciatus zen is essential for serosal tissue function in katatrepsis.
AB  - Unlike most Hox cluster genes, with their canonical role in anterior-posterior
      patterning of the embryo, the Hox3 orthologue of insects has diverged. Here, we
      investigate the zen orthologue in Oncopeltus fasciatus (Hemiptera:Heteroptera).
      As in other insects, the Of-zen gene is expressed extraembryonically, and RNA
      interference (RNAi) experiments demonstrate that it is functionally required in
      this domain for the proper occurrence of katatrepsis, the phase of embryonic
      movements by which the embryo emerges from the yolk and adjusts its orientation
      within the egg. After RNAi knockdown of Of-zen, katatrepsis does not occur,
      causing embryos to complete development inside out. However, not all aspects of
      expression and function are conserved compared to grasshopper, beetle, and fly
      orthologues. Of-zen is not expressed in the extraembryonic tissue until
      relatively late, suggesting it is not involved in tissue specification. Within
      the extraembryonic domain, Of-zen is expressed in the outer serosal membrane, but
      unlike orthologues, it is not detectable in the inner extraembryonic membrane,
      the amnion. Thus, the role of zen in the interaction of serosa, amnion, and
      embryo may differ between species. Of-zen is also expressed in the blastoderm,
      although this early expression shows no apparent correlation with defects seen by
      RNAi knockdown.

PMID- 16460724
TI  - Spatiotemporal characterization of short versus long duration calcium transients
      in embryonic muscle and their role in myofibrillogenesis.
AB  - Intracellular calcium (Ca(2+)) signals are essential for several aspects of
      muscle development, including myofibrillogenesis-the terminal differentiation of
      the sarcomeric lattice. Ryanodine receptor (RyR) Ca(2+) stores must be operative
      during this period and contribute to the production of spontaneous global Ca(2+)
      transients of long duration (LDTs; mean duration approximately 80 s). In this
      study, high-speed confocal imaging of intracellular Ca(2+) in embryonic myocytes
      reveals a novel class of spontaneous Ca(2+) transient. These short duration
      transients (SDTs; mean duration approximately 2 s) are blocked by ryanodine,
      independent of extracellular Ca(2+), insensitive to changes in membrane
      potential, and propagate in the subsarcolemmal space. SDTs arise from RyR stores
      localized to the subsarcolemmal space during myofibrillogenesis. While both LDTs
      and SDTs occur prior to myofibrillogenesis, LDT production ceases and only SDTs
      persist during a period of rapid sarcomere assembly. However, eliminating SDTs
      during this period results in only minor myofibril disruption. On the other hand,
      artificial extension of LDT production completely inhibits sarcomere assembly. In
      conjunction with earlier work, these results suggest that LDTs have at least two
      roles during myofibrillogenesis-activation of sarcoplasmic regulatory cascades
      and regulation of gene expression. The distinct spatiotemporal patterns of LDTs
      versus SDTs may be utilized for differential regulation of cytosolic cascades,
      control of nuclear gene expression, and localized activation of assembly events
      at the sarcolemma.

PMID- 16460725
TI  - Winter air-mass-based synoptic climatological approach and hospital admissions
      for myocardial infarction in Florence, Italy.
AB  - The aim of this study was to evaluate the relationship between the risk of
      hospital admission for myocardial infarction (MI) and the daily weather
      conditions during the winters of 1998-2003, according to an air-mass-based
      synoptic climatological approach. The effects of time lag and 2-day sequences
      with specific air mass types were also investigated. Studies concerning the
      relationship between atmospheric conditions and human health need to take into
      consideration simultaneous effects of many weather variables. At the moment few
      studies have surveyed these effects on hospitalizations for MI. Analyses were
      concentrated on winter, when the maximum peak of hospitalization occurred. An
      objective daily air mass classification by means of statistical analyses based on
      ground meteorological data was carried out. A comparison between air mass
      classification and hospital admissions was made by the calculation of a MI
      admission index, and to detect significant relationships the Mann-Whitney U test,
      the analysis of variance, and the Bonferroni test were used. Significant
      increases in hospital admissions for MI were evident 24h after a day
      characterized by an anticyclonic continental air mass and 6 days after a day
      characterized by a cyclonic air mass. Increased risk of hospitalization was found
      even when specific 2-day air mass sequences occurred. These results represent an
      important step in identifying reliable linkages between weather and health.

PMID- 16460726
TI  - Effects of Sao Paulo air pollution on the upper airways of mice.
AB  - The nose is the first region of the respiratory tract to come in contact with
      airborne pollutants. Previous studies have shown that the nasal mucosa can be
      altered in response to air pollution. In this study, we quantified neutral and
      acidic mucus in three different levels of the nasal cavity of mice exposed to
      ambient levels of air pollution in the city of Sao Paulo, Brazil. Two groups of 6
      day-old male Swiss mice were placed in two exposure chambers. Mice were
      maintained in the chambers 24 h/day, 7 days/week for 5 months. The first chamber
      contained an air filter device (clean chamber; n=20), whereas the second one
      received ambient air pollution (polluted chamber; n=20). We measured the
      concentration of PM(2.5), nitrogen dioxide (NO2), and black carbon inside both
      chambers. The nasal cavity was transversely sectioned at three specific anatomic
      locations (proximal, medial, and distal levels) and submitted to quantitative
      analysis of the amounts of neutral and acidic mucosubstances. We observed a
      37.85% decrease in NO2, 54.77% decrease in PM(2.5), and 100% decrease in black
      carbon concentration in the clean chamber compared to the polluted chamber.
      Significant differences between polluted and clean chambers were observed in the
      epithelium lining the septum of proximal and medial levels of the nasal mucosa,
      with an increase in the percentage of acidic mucus in the polluted chamber
      (P=0.037, proximal level; P=0.023, medial level). We conclude that prolonged
      exposure to low levels of ambient air pollution from an early age shows evidence
      of causing secretory changes in the nasal cavity of mice, with increased
      production of acidic mucosubstances.

PMID- 16460728
TI  - Inflammation markers predicting frailty and mortality in the elderly.
AB  - Greater numbers of individuals are living to older ages. A major concern at both
      individual and population levels is how to live these years at a high functional
      level. If we had physiological markers to identify those at risk for progressive
      functional decline and impeding death, therapies could be targeted towards these
      individuals to prevent adverse outcomes. Senescence is presently considered as
      the consequence of lifelong antigenic stress impinging upon the individual
      genetic background. We might consider inflammation markers as synthetic measures
      of lifelong attrition combined with genetic tendency to develop an inflammatory
      phenotype. Such biomarkers are the most powerful predictors of frailty and
      mortality in the elderly available today. The aim of this review is to translate
      results from the research on ageing into a practical view, suggesting new tools
      for the clinical approach to older people.

PMID- 16460727
TI  - 5-HT1A receptor agonist affects fear conditioning through stimulations of the
      postsynaptic 5-HT1A receptors in the hippocampus and amygdala.
AB  - Evidence from preclinical and clinical studies has shown that 5-HT(1A) receptor
      agonists have anxiolytic actions. The anxiolytic actions of 5-HT(1A) receptor
      agonists have been tested by our previous studies using fear conditioning.
      However, little is known about the brain regions of anxiolytic actions of 5
      HT(1A) receptor agonists in this paradigm. In the present study, we investigated
      the effects of bilateral microinjections of flesinoxan, a selective 5-HT(1A)
      receptor agonist, into the hippocampus, amygdala and medial prefrontal cortex on
      the expression of contextual conditioned freezing and the defecation induced by
      conditioned fear stress in rats. These results reveal that both intrahippocampal
      and intraamygdala injections of flesinoxan decreased the expression of
      conditioned freezing, while injections into the medial prefrontal cortex did not.
      In addition, intraamygdala injection of flesinoxan attenuated the increased
      defecation induced by conditioned fear, but injections into the hippocampus and
      medial prefrontal cortex failed. These results suggest that flesinoxan exerts its
      anxiolytic actions in the fear conditioning through stimulations of the
      postsynaptic 5-HT(1A) receptors in the hippocampus and amygdala.

PMID- 16460729
TI  - Mast cell chymase induces smooth muscle cell apoptosis by disrupting NF-kappaB
      mediated survival signaling.
AB  - Chymase released from activated mast cells induces apoptosis of vascular smooth
      muscle cells (SMCs) in vitro by degrading the pericellular matrix component
      fibronectin, so causing disruption of focal adhesion complexes and Akt
      dephosphorylation, which are necessary for cell adhesion and survival. However,
      the molecular mechanisms of chymase-mediated apoptosis downstream of Akt have
      remained elusive. Here, we show by means of RT-PCR, Western blotting, EMSA,
      immunocytochemistry and confocal microscopy, that chymase induces SMC apoptosis
      by disrupting NF-kappaB-mediated survival signaling. Following chymase treatment,
      the translocation of active NF-kappaB/p65 to the nucleus was partly abolished and
      the amount of nuclear p65 was reduced. Pretreatment of SMCs with chymase also
      inhibited LPS- and IL-1beta-induced nuclear translocation of p65. The chymase
      induced degradation of p65 was mediated by active caspases. Loss of NF-kappaB
      mediated transactivation resulted in downregulation of bcl-2 mRNA and protein
      expression, leading to mitochondrial swelling and release of cytochrome c. The
      apoptotic process involved activation of both caspase 9 and caspase 8. The
      results reveal that, by disrupting the NF-kappaB-mediated survival-signaling
      pathway, activated chymase-secreting mast cells can mediate apoptosis of cultured
      arterial SMCs. Since activated mast cells colocalize with apoptotic SMCs in
      vulnerable areas of human atherosclerotic plaques, they may participate in the
      weakening and rupture of atherosclerotic plaques.

PMID- 16460730
TI  - Alfalfa Mob1-like proteins are involved in cell proliferation and are localized
      in the cell division plane during cytokinesis.
AB  - Mps-one-binder (Mob) proteins play a crucial role in yeast cytokinesis. After
      cloning two Mob1-like genes, MsMob1-A and MsMob1-B from alfalfa (Medicago sativa
      L.) we show that, although they are constitutively expressed in roots, stems,
      leaves, flowers and pods, their transcripts and proteins are mostly produced in
      actively proliferating tissues. A polyclonal antibody specifically raised against
      MsMob1 proteins was used for immunolocalization studies in synchronized root tip
      cells. The subcellular localization of MsMob1-like proteins is demonstrated to be
      cell cycle-regulated. Cytoplasmic localization is faint and diffused during G1
      and S. It becomes concentrated in punctuate and fibrillar structures in G2 as
      well as M phase. At the stage of cytokinesis, the protein is found at the
      emerging cell plate marking the progressive formation of the septum. Mob1
      proteins partially co-localize with microtubules structures functionally related
      to the spindles and important for cytokinesis in eukaryotic cells. The MsMob1
      expression cannot rescue the lethality of the yeast mob1 mutant, suggesting that
      interaction of Mob1 proteins with their effectors may be species-specific.
      Localization of Mob1 proteins in the inner layer of the root cap indicates an
      additional function for this class of proteins in plants, which is likely related
      to the onset of programmed cell death.

PMID- 16460731
TI  - BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor
      nerves and promotes functional recovery after peripheral nerve repair.
AB  - Functional recovery after peripheral nerve injury is often poor despite high
      regenerative capacity of peripheral neurons. In search for novel treatments,
      brief electrical stimulation of the acutely lesioned nerve has recently been
      identified as a clinically feasible approach increasing precision of axonal
      regrowth. The effects of this stimulation appear to be mediated by BDNF and its
      receptor, TrkB, but the down-stream effectors are unknown. A potential candidate
      is the HNK-1 carbohydrate known to be selectively reexpressed in motor but not
      sensory nerve branches of the mouse femoral nerve and to enhance growth of motor
      but not sensory axons in vitro. Here, we show that short-term low-frequency
      electrical stimulation (1 h, 20 Hz) of the lesioned and surgically repaired
      femoral nerve in wild-type mice causes a motor nerve-specific enhancement of HNK
      1 expression correlating with previously reported acceleration of muscle
      reinnervation. Such enhanced HNK-1 expression was not observed after electrical
      stimulation in heterozygous BDNF or TrkB-deficient mice. Accordingly, the degree
      of proper reinnervation of the quadriceps muscle, as indicated by retrograde
      labeling of motoneurons, was reduced in TrkB+/- mice compared to wild-type
      littermates. Also, recovery of quadriceps muscle function, evaluated by a novel
      single-frame motion analysis approach, and axonal regrowth into the distal nerve
      stump, assessed morphologically, were considerably delayed in TrkB+/- mice. These
      findings indicate that BDNF/TrkB signaling is important for functional recovery
      after nerve repair and suggest that up-regulation of the HNK-1 glycan is linked
      to this phenomenon.

PMID- 16460732
TI  - Trypanosoma cruzi: analysis of the complete PUF RNA-binding protein family.
AB  - The members of the PUF family of RNA-binding proteins regulate the fate of mRNAs
      by binding to their 3'UTR sequence elements in eukaryotes. In trypanosomes, for
      which gene expression is polycistronic and controlled almost exclusively by post
      transcriptional processes, PUF proteins could play a crucial role. We report here
      the complete analysis of the PUF protein family of Trypanosoma cruzi composed of
      10 members. In silico analysis predicts the existence of at least three major
      groups within the T. cruzi family, based on their putative binding specificity.
      Using yeast three hybrid assays, we tested some of these predictions for TcPUF1,
      TcPUF3, TcPUF5, and TcPUF8 as representatives of these groups. Data mining of the
      T. cruzi genome led us to describe putative binding targets for the TcPUFs of the
      most conserved group, TcPUF1 and TcPUF2. The targets include genes for
      mitochondrial proteins and protein kinases. Finally, immunolocalization
      experiments showed that TcPUF1 is localized in multiple discrete foci in the
      cytoplasm supporting its proposed function.

PMID- 16460733
TI  - The role of tryptophan 272 in the Paracoccus denitrificans cytochrome c oxidase.
AB  - The mechanism of electron coupled proton transfer in cytochrome c oxidase (CcO)
      is still poorly understood. The P(M)-intermediate of the catalytic cycle is an
      oxoferryl state whose generation requires one additional electron, which cannot
      be provided by the two metal centres. The missing electron has been suggested to
      be donated to this binuclear site by a tyrosine residue. A tyrosine radical
      species has been detected in the P(M) and F* intermediates (formed by addition of
      H2O2) of the Paraccocus denitrificans CcO using electron paramagnetic resonance
      (EPR) spectroscopy. From the study of conserved variants its origin was
      determined to be Y167 which is surprising as this residue is not part of the
      active site. Upon inspection of the active site it becomes evident that W272
      could be the actual donor of the missing electron, which can then be replenished
      from Y167 or from the Y280-H276 cross link in the natural cycle. To address the
      question, whether such a direct electron transfer pathway to the binuclear centre
      exists two tryptophan 272 variants in subunit I have been generated. These
      variants are characterised by their turnover rates as well as using EPR and
      optical spectroscopy. From these experiments it is concluded, that W272 is an
      important intermediate in the formation of the radical species appearing in P(M)
      and F* intermediates produced with hydrogen peroxide. The significance of this
      finding for the catalytic function of the enzyme is discussed.

PMID- 16460734
TI  - Blind docking of drug-sized compounds to proteins with up to a thousand residues.
AB  - Blind docking was introduced for the detection of possible binding sites and
      modes of peptide ligands by scanning the entire surface of protein targets. In
      the present study, the method is tested on a group of drug-sized compounds and
      proteins with up to a thousand amino acid residues. Both proteins from complex
      structures and ligand-free proteins were used as targets. Robustness, limitations
      and future perspectives of the method are discussed. It is concluded that blind
      docking can be used for unbiased mapping of the binding patterns of drug
      candidates.

PMID- 16460735
TI  - Clathrin light chain b is capable of affecting potently a major protein
      phosphatase from microtubules (MT-PP1).
AB  - Clathrin light chain (CL) b purified from bovine brain postmicrotubule
      supernatant and identified by mass spectrometry potently inhibited a catalytic
      activity of a major protein phosphatase (PP) that was copurified with
      microtubules and recognized by antiPP1 antibodies. CLb similarly affected the
      catalytic subunit and holoenzyme of the PP, little inhibiting the activity of
      PP2A. Although the CLb from clathrin-coated vesicles was several hundredfold
      weaker than our purified CLb, the CLb in the postmicrotubule supernatant,
      independent of whether it was sedimentable or soluble, was as active as the
      purified CLb. Thus CLb may be a potent regulator of the PP.

PMID- 16460736
TI  - Hydrogen peroxide is a mediator of indole-3-acetic acid/horseradish peroxidase
      induced apoptosis.
AB  - Recently, we reported that a combination of indole-3-acetic acid (IAA) and
      horseradish peroxidase (HRP) induces apoptosis in G361 human melanoma cells.
      However, the apoptotic mechanism involved has been poorly studied. It is known
      that when IAA is oxidized by HRP, free radicals are produced, and since oxidative
      stress can induce apoptosis, we investigated whether reactive oxygen species
      (ROS) are involved in IAA/HRP-induced apoptosis. Our results show that IAA/HRP
      induced free radical production is inhibited by catalase, but not by superoxide
      dismutase or sodium formate. Furthermore, catalase was found to prevent IAA/HRP
      induced apoptotic cell death, indicating that IAA/HRP-produced hydrogen peroxide
      (H2O2) may be involved in the apoptotic process. Moreover, the antiapoptotic
      effect of catalase is potentiated by NADPH, which is known to protect catalase.
      On further investigating the IAA/HRP-mediated apoptotic pathway, we found that
      the IAA/HRP reaction leads to caspase-3 activation and poly(ADP-ribose)
      polymerase (PARP) cleavage, which was also blocked by catalase. Additionally, we
      found that IAA/HRP produces H2O2 and induces peroxiredoxin (Prx) sulfonylation.
      Consequently, our results suggest that H2O2 plays a major role in IAA/HRP-induced
      apoptosis.

PMID- 16460737
TI  - Photochemically enhanced cellular delivery of cell penetrating peptide-PNA
      conjugates.
AB  - Recent studies have shown that endosomal release is a major rate-limiting step
      for cellular delivery via a variety of cationic cell penetrating peptides. Thus,
      methods and/or protocols for effective release of endosomally entrapped drugs are
      highly warranted. Photochemical internalization (PCI) has previously been
      proposed for this purpose. Here, we demonstrate an enhancement of up to two
      orders of magnitude of the antisense effects (cytosolic/nuclear) of peptide
      nucleic acid-peptide conjugates (Tat, Arg7, KLA) in HeLa cells by a PCI approach
      using the photosensitizer AlPc2a. These results emphasize the importance of
      endosomal release for cellular activity of this type of drug delivery and also
      raise hope that methods like PCI which have applications for in vivo use may also
      enhance the bioavailability and in vivo efficacy of these types of conjugates.

PMID- 16460738
TI  - In vitro and in vivo studies on CCR10 regulation by Annexin A1.
AB  - The mode of action of annexin A1 (ANXA1) is poorly understood. By using rapid
      subtraction hybridization we studied the effects of human recombinant ANXA1 and
      the N-terminal ANXA1 peptide on gene expression in a human larynx cell line.
      Three genes showed strong downregulation after treatment with ANXA1. In contrast,
      expression of CCR10, a seven transmembrane G-protein coupled receptor for
      chemokine CCL27 involved in mucosal immunity, was increased. Moreover the
      reduction in CCR10 expression induced by ANXA1 gene deletion was rescued by
      intravenous treatment with low doses of ANXA1. These findings provide new
      evidence that ANXA1 modulates gene expression.

PMID- 16460739
TI  - Rapid inhibition of female sexual behavior by gonadotropin-inhibitory hormone
      (GnIH).
AB  - Gonadotropin-releasing hormone (GnRH) is largely responsible for the initiation
      of sexual behaviors; one form of GnRH activates a physiological cascade causing
      gonadal growth and gonadal steroid feedback to the brain, and another form is
      thought to act as a neurotransmitter to enhance sexual receptivity. In contrast
      to GnRH, gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin release.
      The distribution of GnIH in the avian brain suggests that it has not only
      hypophysiotropic actions but also unknown behavioral actions. GnIH fibers are
      present in the median eminence (ME) and are in apparent contact with chicken GnRH
      (cGnRH)-I and -II neurons and fibers. In birds, cGnRH-I regulates pituitary
      gonadotropin release, whereas cGnRH-II enhances copulation solicitation in
      estradiol-primed females exposed to male song. In the present study, we
      determined the effects of GnIH administered centrally to female white-crowned
      sparrows. A physiological dose of GnIH reduced circulating LH and inhibited
      copulation solicitation, without affecting locomotor activity. Using rhodaminated
      GnIH, putative GnIH binding sites were seen in the ME close to GnRH-I fiber
      terminals and in the midbrain on or close to GnRH-II neurons. These data
      demonstrate direct effects of GnIH upon reproductive physiology and behavior,
      possibly via separate actions on two forms of GnRH.

PMID- 16460740
TI  - Menopausal estrogen therapy counteracts normal aging effects on intima thickness,
      media thickness and intima/media ratio in carotid and femoral arteries. An
      investigation using noninvasive high-frequency ultrasound.
AB  - BACKGROUND: Estrogen therapy that is started at the time of menopause seems to
      protect against the development of atherosclerosis and cardiovascular diseases,
      in contrast to the initial increased cardiovascular risk when hormone therapy is
      initiated in older women. With increased aging and degree of atherosclerosis, the
      thickness of the artery intima increases and that of the media decreases. These
      changes can be noninvasively estimated using high-frequency ultrasound. METHODS
      AND RESULTS: The thickness of carotid and femoral artery intima and media was
      assessed, using noninvasive high-frequency ultrasound (25MHz). Long-term estrogen
      users (mean treatment duration 20 years) had a significantly thinner mean carotid
      intima layer (-25%; P=0.0002), a thicker media layer (+74%; P=0.0002) and a
      substantially lower intima/media thickness ratio (-54%; P<0.0001) than 17 age
      matched nonusers, with values closer to those in 20 premenopausal women. Similar
      but less pronounced differences between the postmenopausal groups were found for
      the femoral artery. CONCLUSIONS: A preserved thin artery wall intima and a low
      intima/media thickness ratio, at values close to those in young women might be
      partially responsible for the beneficial cardiovascular effects of estrogen
      therapy when it is initiated at the time of menopause.

PMID- 16460741
TI  - Evaluation of fusion between liposomes and erythrocytes for intracellular
      derivatization of amino acids in cells.
AB  - Erythrocytes were fused with liposome for intracellular derivatization of amino
      acids in cells. The fusion efficiency was evaluated with capillary
      electrophoresis (CE) and laser-induced fluorescence (LIF) detection. Reagent
      fluorescein isothiocyanate (FITC) was enveloped in liposomes and introduced into
      erythrocytes by fusion between liposomes and erythrocytes. The amino acids in the
      fused cells were derivated by the introduced FITC and the derivated amino acids
      were extracted for detection by capillary electrophoresis equipped with laser
      induced fluorescence detector. The fusion conditions were investigated. It was
      found that incubation of liposome and erythrocytes in the presence of 13%
      polyethylene glycol 6000 (PEG 6000) for 15min produced the highest fusion
      efficiency and kept the erythrocytes stability.

PMID- 16460742
TI  - Isocratic and gradient elution chromatography: a comparison in terms of speed,
      retention reproducibility and quantitation.
AB  - Chromatographers are cautioned to avoid gradient elution when isocratic elution
      will do. In this work, we compared the analytical properties of gradient and
      isocratic separations of a sample which can be done quite readily under isocratic
      conditions. We found that gradient elution gave a shorter overall analysis with
      similar resolution of the critical pair compared to isocratic elution without
      sacrificing repeatability in retention time, peak area and peak height or
      linearity of the calibration curve. We also obtained acceptable repeatability in
      peak area/height and linearity of calibrations curves for a sample that required
      gradient elution using a practical baseline subtraction technique. Based on these
      results and related work which show that columns can be reequilibrated by
      flushing with less than two column volumes of the initial eluent, we conclude
      that many of the reasons given to avoid gradient elution deserve serious
      reconsideration, especially for those samples which are easily separated
      isocratically. However, we believe isocratic elution will remain preferable when:
      (1) the sample contains less than 10 weakly retained components (i.e. the last
      peak elutes with k' < 5) or (2) the gradient baseline impedes trace analysis.

PMID- 16460743
TI  - Aqueous chromatography system using pH- and temperature-responsive stationary
      phase with ion-exchange groups.
AB  - We report on the development of a novel analytical HPLC technique of nonsteroidal
      anti-inflammatory drugs (NSAIDs), such as ibuprofen, ketoprofen and naproxen,
      with an isocratic aqueous mobile phase. In this study, we designed a new pH- and
      temperature-responsive copolymer of N-isopropylacrylamide (NIPAAm), butyl
      methacrylate (BMA) and N,N-dimethylaminopropylacrylamide (DMAPAAm). The copolymer
      was modified with cross-linked poly(NIPAAm-co-BMA-co-DMAPAAm) (IBD) hydrogel on
      to aminopropyl silica beads, and the products were evaluated as HPLC packing
      materials for an ion-exchange- and temperature-responsive chromatography. The
      property of the surface of the stationary phase was altered from hydrophilic to
      hydrophobic, and from charged to non-charged by changes in the temperature and
      pH. In addition, it is possible that ion-exchange groups can appear or be hidden
      on the polymer chain surface by temperature changes. The interactions of NSAIDs
      with this stationary phase were controlled by the temperature and the pH with a
      constant aqueous mobile phase. PH- and temperature-responsive chromatography is
      expected to be useful for the separation of pharmaceuticals and biomolecules.

PMID- 16460744
TI  - Surface characterization of poly(methyl methacrylate-co-n-butyl acrylate-co
      cyclopentylstyryl-polyhedral oligomeric silsesquioxane) by inverse gas
      chromatography.
AB  - The surface properties of poly(methyl methacrylate-co-n-butyl acrylate-co
      cyclopentylstyryl polyhedral oligomeric silsesquioxane) (poly(MMA-co-BA-co-styryl
      POSS)) were studied by means of inverse gas chromatography (IGC) using 10 non
      polar and polar solvents as the probes. Thermodynamic parameters of adsorption,
      e.g., specific retention volume, the dispersive component of the surface free
      energy, the specific interaction contribution to the free energy of adsorption
      and the acid/base constants were obtained to investigate the interactions between
      the surfaces of the copolymers and different solvents. It was found that
      incorporation of styryl-POSS into polymer resulted in increasing interactions
      between polymers and solvents, dispersive component of surface free energy of
      polymer and acidity of the surfaces of the polymers. The more the styryl-POSS
      were embedded, the stronger the interaction between the polymer surface and
      solvent, the dispersive component of the surface free energy and the acidity of
      the polymer surface were.

PMID- 16460746
TI  - Structure elucidation of deoxylutein II isomers by on-line capillary high
      performance liquid chromatography-(1)H nuclear magnetic resonance spectroscopy.
AB  - Thermal and iodine-catalyzed photochemical (Z/E)-isomerization of deoxylutein II
      [(3R,6'R)-3-hydroxy-3',4'-didehydro-beta,gamma-carotene, anhydrolutein I] (2),
      the dehydration product of lutein [(3R,3'R,6'R)-beta,epsilon-carotene-3,3'-diol]
      (4), yielded multi-component mixtures of (Z)-isomers. By I(2)-catalyzed
      photoisomerization, (9Z)-2, (9'Z)-2, (13Z)-2, (13'Z)-2 and (15Z)-2 are generated
      as main products. In addition, this thermodynamic-equilibrium mixture contains
      traces of (9Z,9'Z)-2 and other (di-Z)-isomers in minor concentrations. Thirteen
      isomers are chromatographically separated and detected on-line by UV-vis and mass
      spectrometry. (all-E)-Deoxylutein II (2) and six of its (Z)-configured isomers
      are separated by capillary HPLC (acetone-d(6)/D(2)O = 85:15) and detected on-line
      by (1)H NMR spectroscopy in a microprobe. With the microprobe and the active
      detection volume of 1.5 microl, it is possible to perform structure elucidation
      with very small amounts available for various (Z)-isomers of deoxylutein II (2)
      in the isomerization mixture.

PMID- 16460747
TI  - Prediction of gas chromatographic retention of polyunsaturated fatty acid methyl
      esters.
AB  - Multivariate regression models were applied to predict retention indices as
      equivalent chain lengths (ECL) for methylene-interrupted polyunsaturated fatty
      acids. Simple molecular descriptors, the chain length, the number of double bonds
      and the position of the double bond system, were used as predictors. The merits
      of different variable combinations were evaluated. For general models, it was
      necessary to include the distance from the double bond system to both the
      carbonyl group (Delta-position) and the methyl end of the fatty acid (n
      position). The best accuracy was found for models including higher order terms of
      Delta and n. For models restricted to n-3 and n-6 isomers, it was not necessary
      to include the n-position among the variables. The highest residuals for the most
      accurate models were below 0.06 ECL units, and root mean square error of
      prediction was below 0.030. The ECL data was achieved by three different
      temperature programs on a cyanopropyl column.

PMID- 16460749
TI  - Thermo-induced formation of physical "cross-linking points" of PNIPAM-g-PEO in
      semidilute aqueous solutions.
AB  - Linear poly(N-isopropylacrylamide) chains grafted with short poly(ethylene oxide)
      chains (PNIPAM-g-PEO) were prepared by free radical copolymerization of NIPAM and
      PEO macromonomers (M(w) = 5000 g/mol) end-capped with methacrylate in water.
      Temperature effects on the solution viscosity of thermally sensitive copolymer
      were studied in different aqueous concentrations. A specific transition was
      observed during the measurement of the reduced viscosities of PNIPAM-g-PEO
      copolymer at a certain concentration (C0) in semidilute aqueous solutions: the
      reduced viscosities increased sharply (namely, thermothickening behavior) at LCST
      when concentrations were higher than C0, or decreased sharply at LCST when
      concentrations lower than C0. A plateau was also found near C0 when temperature
      was closing to LCST from low temperature, showing there is no change in reduced
      viscosity under this circumstance. The inverse increase of the viscosities at
      higher temperatures in higher concentration (> approximately 3 g/L) is attributed
      to the forming of physical "cross-linking points" composed of collapsed PNIPAM
      core and expanded PEO shell. The sharp decrease of the viscosities at higher
      temperatures in lower concentration (< approximately 3 g/L) is attributed to the
      forming of independent globules. The plateau could be attributed to the
      equilibrium competition between forming of physical "cross-linking points" and
      independent globules depending on the copolymer solution concentrations.

PMID- 16460748
TI  - Fully automated liquid chromatography-mass spectrometry determination of 17beta
      estradiol in river water.
AB  - Surface modified molecularly imprinted polymers (SM-MIPs) for 17beta-estradiol
      (E2), utilizing 6-ketoecradiol as a pseudo template were prepared. MIPs for E2
      were synthesized using 4-vinyl pyridine and ethylene dimethacrylate as a
      functional monomer and cross-linking agent, respectively. MIPs selectively
      retained E2 and provided excellent chromatographic resolution from interfering
      compounds inherent in river water sample matrices. Therefore, freshly prepared
      MIPs were applied to quantitative mass spectrometric (negative electrospray
      ionization mode) detection of low levels of E2 in river water sample. In order to
      pre-concentrate the target compound for HPLC analysis, column switching was
      coupled with a pretreatment column packed with the MIPs. The repeatability of
      actual determinations of river water sample, in which background E2 was not
      detected, spiked with 50 ng/L of E2 was 2.2% RSD with a detection limit and
      qualification limit of 1.8 and 5.4 ng/L, respectively. Surface modification of
      MIP particlefs packed in the pretreatment column provided selective affinity and
      on-line concentration of low levels of E2 while simultaneously eliminating sample
      matrix interference, resulting in a significant increase in sensitivity and
      reproducibility for liquid chromatography-mass spectrometry analysis of E2 in
      river water sample.

PMID- 16460750
TI  - Dependence of the broad frequency dielectric spectra of colloidal polystyrene
      particle suspensions on the difference between the counterion and co-ion
      diffusion coefficients.
AB  - Dielectric properties of four suspensions of spherical polystyrene particles were
      measured at 25 degrees C over a broad frequency range extending from 100 Hz to 10
      MHz, using a HP 4192 A Impedance Analyzer. The instrument was coupled to a cell
      with parallel platinum black electrodes and variable spacing, and the quadrupole
      calibration method was used. The aqueous electrolyte solutions were prepared
      using equal concentrations of NaCl, KCl, NaAc, or KAc, so that the calculated
      Debye screening length and Zeta potential remained constant, while the
      conductivity changed. The polystyrene particles used (Interfacial Dynamics Corp.,
      surfactant-free white sulfate latex) have a diameter of 1 micron and a surface
      charge density that is independent of the pH. The dielectric spectra were
      described using the Nettelblad-Niklasson expression combined with a Debye type
      high-frequency term and analyzed using the Shilov-Dukhin theory and numerical
      results. The theoretical prediction that the low-frequency dispersion parameters
      are determined by the co-ion diffusion coefficient was experimentally confirmed.
      This also allowed to justify an alternative definition of the characteristic time
      of the low-frequency dispersion. On the contrary, the prediction that the high
      frequency dispersion parameters are determined by the diffusion coefficient of
      counterions could not be confirmed, possibly due to experimental problems.
      However, the zeta-potential values deduced from high-frequency data were
      compatible with values deduced from electrophoretic mobility measurements.

PMID- 16460751
TI  - Excitation-contraction coupling in the MLP knockout mouse.

PMID- 16460752
TI  - Crystal structures of human glycerol 3-phosphate dehydrogenase 1 (GPD1).
AB  - Homo sapiens L-alpha-glycerol-3-phosphate dehydrogenase 1 (GPD1) catalyzes the
      reversible biological conversion of dihydroxyacetone (DHAP) to glycerol-3
      phosphate. The GPD1 protein was expressed in Escherichia coli, and purified as a
      fusion protein with glutathione S-transferase. Here we report the apoenzyme
      structure of GPD1 determined by multiwavelength anomalous diffraction phasing,
      and other complex structures with small molecules (NAD+ and DHAP) by the
      molecular replacement method. This enzyme structure is organized into two
      distinct domains, the N-terminal eight-stranded beta-sheet sandwich domain and
      the C-terminal helical substrate-binding domain. An electrophilic catalytic
      mechanism by the epsilon-NH3+ group of Lys204 is proposed on the basis of the
      structural analyses. In addition, the inhibitory effects of zinc and sulfate on
      GPDHs are assayed and discussed.

PMID- 16460754
TI  - The disaggregation activity of the mitochondrial ClpB homolog Hsp78 maintains
      Hsp70 function during heat stress.
AB  - Molecular chaperones are important components of mitochondrial protein biogenesis
      and are required to maintain the organellar function under normal and stress
      conditions. We addressed the functional role of the Hsp100/ClpB homolog Hsp78
      during aggregation reactions and its functional cooperation with the main
      mitochondrial Hsp70, Ssc1, in mitochondria of the yeast Saccharomyces cerevisiae.
      By establishing an aggregation/disaggregation assay in intact mitochondria we
      demonstrated that Hsp78 is indispensable for the resolubilization of protein
      aggregates generated by heat stress under in vivo conditions. The ATP-dependent
      disaggregation activity of Hsp78 was capable of reversing the preprotein import
      defect of a destabilized mutant form of Ssc1. This role in disaggregation of Ssc1
      is unique for Hsp78, since the recently identified, Hsp70-specific chaperone
      Zim17 had no effect on the resolubilization reaction. We observed only a minor
      effect of the second mitochondrial Hsp100 family member Mcx1 on protein
      disaggregation. A "holding" activity of the mitochondrial Hsp70 system was a
      prerequisite for a successful resolubilization of aggregated proteins. We
      conclude that the protective role of Hsp78 in thermotolerance is mainly based on
      maintaining the molecular chaperone Ssc1 in a soluble and functional state.

PMID- 16460753
TI  - Scanning mutagenesis studies reveal multiple distinct regions within the human
      protein kinase C alpha regulatory domain important for phorbol ester-dependent
      activation of the enzyme.
AB  - While phorbol ester-binding sites within protein kinase C alpha (PKCalpha) have
      been identified and characterized utilizing fragments of the enzyme, it remains
      unclear whether additional regions within the enzyme may play an important role
      in its ability to be activated by phorbol ester. To examine this hypothesis, we
      generated 20 glutathione-S-transferase-tagged, V1-deficient, human PKCalpha
      holoenzyme constructs in which tandem six or 12 amino acid residue stretches
      along the full regulatory domain were changed to alanine residues. Each protein
      was assessed for its ability to bind phorbol ester and to induce growth
      repression when its catalytic activity was activated by phorbol ester upon
      expression in yeast cells. Mutagenesis of residues 99-158 potently reduced
      phorbol binding, consistent with previously published findings on the importance
      of the C1b region in phorbol binding. In addition, we identified a number of
      regions within the PKC regulatory domain that, when mutagenized, blocked the
      activation of PKC-mediated growth repression by phorbol ester while actually
      enhancing phorbol ester binding in vitro (residues 33-62, and 75-86). This study
      thus helps distinguish regions important for phorbol binding from regions
      important for the ability of phorbol ester to activate the enzyme. Our findings
      also suggest that multiple regions within C2 are necessary for full activation of
      the enzyme by phorbol ester, in particular residues 231-254. Finally, three
      regions, when mutagenized, completely, blocked catalytic domain activity in vivo
      (residues 33-62, 75-86, and 123-146), underscoring the important role of
      regulatory domain sequences in influencing catalytic domain function, even in the
      absence of the V1 region containing the pseudosubstrate sequence. This is the
      first tandem mutagenesis study for PKC that assesses the importance of regions
      for both phorbol binding and for phorbol-dependent activation in the context of
      the entire holoenzyme.

PMID- 16460755
TI  - Time-resolved small-angle X-ray scattering investigation of the folding dynamics
      of heme oxygenase: implication of the scaling relationship for the submillisecond
      intermediates of protein folding.
AB  - Polypeptide collapse is generally observed as the initial folding dynamics of
      proteins with more than 100 residues, and is suggested to be caused by the coil
      globule transition explained by Flory's theory of polymers. To support the
      suggestion by establishing a scaling behavior between radius of gyration (Rg) and
      chain length for the initial folding intermediates, the folding dynamics of heme
      oxygenase (HO) was characterized by time-resolved, small-angle X-ray scattering.
      HO is a highly helical protein without disulfide bridges, and is the largest
      protein (263 residues) characterized by the method. The folding process of HO was
      found to contain a transient oligomerization; however, the conformation within 10
      ms was demonstrated to be monomeric and to possess Rg of 26.1(+/-1.1) A. Together
      with the corresponding data for proteins with different chain lengths, the seven
      Rg values demonstrated the scaling relationship to chain length with a scaling
      exponent of 0.35+/-0.11, which is close to the theoretical value of 1/3 predicted
      for globules in solutions where monomer-monomer interactions are favored over
      monomer-solvent interactions (poor solvent). The finding indicated that the
      initial folding dynamics of proteins bears the signature of the coil-globule
      transition, and offers a clue to explain the folding mechanisms of proteins with
      different chain lengths.

PMID- 16460756
TI  - Dodecins: a family of lumichrome binding proteins.
AB  - Dodecin is a small dodecameric flavoprotein from Halobacterium salinarum that
      contains two flavins stacked between two tryptophan residues to form an aromatic
      tetrade. The functional properties of heterologously expressed dodecin were
      investigated by fluorescence spectroscopy, which allowed the determination of
      dissociation constants for a number of protein-ligand complexes. The values
      obtained were in the nanomolar to micromolar range and correlate positively with
      the ligand size. These data were supplemented by X-ray crystal structures of the
      apododecin and holocomplexes with lumichrome, lumiflavin, riboflavin and FMN at
      resolutions between 1.55 to 1.95 A to unravel a gating mechanism as the
      structural basis for the preferential binding of the small ligands lumichrome and
      lumiflavin. The detailed analysis of the dodecin manifold for preferential
      binding of lumichrome and lumiflavin provides insight on a subatom level into a
      protein's strategy to gain selectivity for low molecular mass compounds by steric
      restrictions rather than specific interactions. Investigations on the ligand
      composition of a wild-type dodecin crystal (1.32 A resolution) support
      conclusions of functional and structural investigations on heterologously
      expressed dodecin, and strongly suggest that lumichrome, a molecule associated
      with the flavin metabolism, is a ligand of dodecin in vivo. Studies on mutant
      protein and a Halorhodospira halophila homologue spread the idea of a lumichrome
      binding system as a possible "waste"-trapping device, widely distributed in
      prokaryotes.

PMID- 16460757
TI  - Sequence requirements for Lon-dependent degradation of the Escherichia coli
      transcription activator SoxS: identification of the SoxS residues critical to
      proteolysis and specific inhibition of in vitro degradation by a peptide
      comprised of the N-terminal 21 amino acid residues.
AB  - When Escherichia coli encounter redox-cycling compounds that endogenously
      generate superoxide, the cell's defense response is initiated by the de novo
      synthesis of SoxS, which then activates transcription of the genes of the SoxRS
      regulon. Recently, we showed that after the oxidative stress is relieved, the
      SoxRS system resets by an active process wherein SoxS synthesis ceases and the
      intrinsically unstable SoxS protein is rapidly degraded, primarily by Lon
      protease. Here, we use deletion mutants and a library of alanine-stretch mutants
      of the entire protein to identify the SoxS features responsible for Lon-dependent
      proteolysis in vivo. We found that the 17 amino acid residues at the SoxS N
      terminus play the primary role in protease recognition and that the addition of
      the N-terminal 21 residues of SoxS to the otherwise stable green fluorescent
      protein is sufficient to signal the chimera for Lon-dependent degradation. With a
      minimal in vitro degradation system, we confirm the intrinsic instability of SoxS
      and the sequence requirements for Lon-dependent degradation. Lastly, we
      demonstrate that the addition of a peptide comprised of the 21 N-terminal amino
      acid residues of SoxS is able to inhibit specifically the in vitro proteolysis of
      SoxS.

PMID- 16460758
TI  - Crystal structure of Pseudomonas aeruginosa SPM-1 provides insights into variable
      zinc affinity of metallo-beta-lactamases.
AB  - Metallo-beta-lactamases (mbetals) confer broad-spectrum resistance to beta-lactam
      antibiotics upon host bacteria and escape the action of existing beta-lactamase
      inhibitors. SPM-1 is a recently discovered mbetal that is distinguished from
      related enzymes by possession of a substantial central insertion and by sequence
      variation at positions that maintain active site structure. Biochemical data show
      SPM-1 to contain two Zn2+ sites of differing affinities, a phenomenon that is
      well documented amongst mbetals but for which a structural explanation has proved
      elusive. Here, we report the crystal structure of SPM-1 to 1.9 A resolution. The
      structure reveals SPM-1 to lack a mobile loop implicated in substrate binding by
      related mbetals and to accommodate the central insertion in an extended helical
      interdomain region. Deleting this had marginal effect upon binding and hydrolysis
      of a range of beta-lactams. These data suggest that the interactions of SPM-1
      with substrates differ from those employed by other mbetals. SPM-1 as
      crystallised contains a single Zn2+. Both the active site hydrogen-bonding
      network and main-chain geometry at Asp120, a key component of the binding site
      for the second zinc ion, differ significantly from previous mbetal structures. We
      propose that variable interactions made by the Asp120 carbonyl group modulate
      affinity for a second Zn2+ equivalent in mbetals of the B1 subfamily. We further
      predict that SPM-1 possesses the capacity to evolve variants of enhanced
      catalytic activity by point mutations altering geometry and hydrogen bonding in
      the vicinity of the second Zn2+ site.

PMID- 16460759
TI  - Solution scattering reveals large differences in the global structures of type II
      protein kinase A isoforms.
AB  - Isoform diversity within the protein kinase A (PKA) family is achieved by
      catalytic (C) subunits binding to different isoforms of regulatory subunit
      homodimers (R2). In a previous small-angle X-ray scattering study, we showed that
      the type Ialpha R2 homodimer has a distinctive Y-shaped structure, while the
      IIalpha and IIbeta homodimers are highly flexible and extended in solution. Here
      we present the results of X-ray scattering experiments on different isoforms of
      the PKA holoenzyme (R2C2) and show that the type IIbeta R2 homodimer undergoes a
      dramatic compaction upon binding C subunits that involves a 10A reduction in
      radius of gyration (from 56 to 46 A) and a 35 A shortening of the maximum linear
      dimension (from 180-145 A). In contrast, the type IIalpha R2 homodimer shows very
      little change in these structural parameters and remains extended upon C-subunit
      binding. This large difference is surprising given the highly conserved sequence
      and domain organization for the different R isoforms. A mutant RIIbeta holoenzyme
      and an RIIalpha/RIIbeta chimera were used to explore the role of the sequence
      linking different functional domains within RIIbeta in the observed C subunit
      induced compaction. Structural modeling was used to aid in interpreting the
      scattering results in terms of the role of inter-domain and inter-subunit
      contacts in determining the global conformations of the different isoforms. The
      results provide an important structural foundation for understanding isoform
      specific PKA localization and signaling.

PMID- 16460760
TI  - Prevalence of psychiatric morbidity and psychological adaptation of the nurses in
      a structured SARS caring unit during outbreak: a prospective and periodic
      assessment study in Taiwan.
AB  - To assess the rapidly changing psychological status of nurses during the acute
      phase of the 2003 SARS outbreak, we conducted a prospective and periodic
      evaluation of psychiatric morbidity and psychological adaptation among nurses in
      SARS units and non-SARS units. Nurse participants were from two SARS units
      (regular SARS [N=44] and SARS ICU [N=26]) and two non-SARS units (Neurology
      [N=15] and CCU [N=17]). Participants periodically self-evaluated their
      depression, anxiety, post-traumatic stress symptoms, sleep disturbance, attitude
      towards SARS and family support. Results showed that depression (38.5% vs. 3.1%)
      and insomnia (37% vs. 9.7%) were, respectively, greater in the SARS unit nurses
      than the non-SARS unit nurses. No difference between these two groups was found
      in the prevalence of post-traumatic stress symptoms (33% vs. 18.7%), yet, three
      unit subjects (SARS ICU, SARS regular and Neurology) had significantly higher
      rate than those in CCU (29.7% vs. 11.8%, respectively) (p<0.05). For the SARS
      unit nurses, significant reduction in mood ratings, insomnia rate and perceived
      negative feelings as well as increasing knowledge and understanding of SARS at
      the end of the study (all p<0.001) indicated that a gradual psychological
      adaptation had occurred. The adjustment of nurses in the more structured SARS ICU
      environment, where nurses care for even more severely ill patients, may have been
      as good or better than that of nurses in the regular SARS unit. Occurrence of
      psychiatric symptoms was linked to direct exposure to SARS patient care, previous
      mood disorder history, younger age and perceived negative feelings. Positive
      coping attitude and strong social and family support may have protected against
      acute stress. In conclusion, the psychological impact on the caring staffs facing
      future bio-disaster will be minimized with lowered risk factors and a safer and
      more structured work environment.

PMID- 16460762
TI  - Modeling of ATP-mediated signal transduction and wave propagation in astrocytic
      cellular networks.
AB  - Astrocytes, a special type of glial cells, were considered to have supporting
      role in information processing in the brain. However, several recent studies have
      shown that they can be chemically stimulated by neurotransmitters and use a form
      of signaling, in which ATP acts as an extracellular messenger. Pathological
      conditions, such as spreading depression, have been linked to abnormal range of
      wave propagation in astrocytic cellular networks. Nevertheless, the underlying
      intra- and inter-cellular signaling mechanisms remain unclear. Motivated by the
      above, we constructed a model to understand the relationship between single-cell
      signal transduction mechanisms and wave propagation and blocking in astrocytic
      networks. The model incorporates ATP-mediated IP3 production, the subsequent Ca2+
      release from the ER through IP3R channels and ATP release into the extracellular
      space. For the latter, two hypotheses were tested: Ca2+- or IP3-dependent ATP
      release. In the first case, single astrocytes can exhibit excitable behavior and
      frequency-encoded oscillations. Homogeneous, one-dimensional astrocytic networks
      can propagate waves with infinite range, while in two dimensions, spiral waves
      can be generated. However, in the IP3-dependent ATP release case, the specific
      coupling of the driver ATP-IP3 system with the driven Ca2+ subsystem leads to one
      and two-dimensional wave patterns with finite range of propagation.

PMID- 16460761
TI  - Spinal cord stroke in a ballet dancer.
AB  - Fibrocartilaginous embolism of the intervertebral disc represents an uncommon
      cause of spinal cord infarction. We present the case of a previously healthy 30
      year old ballet dancer who noted acute severe neck pain shortly after an
      intensive training session and developed weakness and numbness of both arms, as
      well as difficulties in emptying the bladder and bowel. Her clinical presentation
      and neuroimaging studies including diffusion weighted imaging were consistent
      with a spinal cord infarction in the anterior spinal territory at the C3-C6
      spinal cord level. Although no histological confirmation was obtained, lack of
      evidence of other plausible diagnoses in the setting of the patient's clinical
      presentation and neuroimaging findings made fibrocartilaginous embolism the most
      likely etiopathogenetic mechanism of spinal stroke.

PMID- 16460763
TI  - The adaptive dynamics of function-valued traits.
AB  - This study extends the framework of adaptive dynamics to function-valued traits.
      Such adaptive traits naturally arise in a great variety of settings: variable or
      heterogeneous environments, age-structured populations, phenotypic plasticity,
      patterns of growth and form, resource gradients, and in many other areas of
      evolutionary ecology. Adaptive dynamics theory allows analysing the long-term
      evolution of such traits under the density-dependent and frequency-dependent
      selection pressures resulting from feedback between evolving populations and
      their ecological environment. Starting from individual-based considerations, we
      derive equations describing the expected dynamics of a function-valued trait in
      asexually reproducing populations under mutation-limited evolution, thus
      generalizing the canonical equation of adaptive dynamics to function-valued
      traits. We explain in detail how to account for various kinds of evolutionary
      constraints on the adaptive dynamics of function-valued traits. To illustrate the
      utility of our approach, we present applications to two specific examples that
      address, respectively, the evolution of metabolic investment strategies along
      resource gradients, and the evolution of seasonal flowering schedules in
      temporally varying environments.

PMID- 16460764
TI  - Requirement for multiple activation signals by anti-inflammatory feedback in
      macrophages.
AB  - Pathogen killing is one of the primary roles of macrophages, utilizing potent
      effectors such as nitric oxide (NO) and involving other cellular machinery
      including iron regulatory apparatus. Macrophages become strongly activated upon
      receipt of appropriate signaling with cytokines and pathogen-derived endotoxins.
      However, they must resist activation in the absence of decisive signaling due to
      the energetic demands of activation coupled with the toxic nature of effector
      molecules to surrounding tissues. We have developed a mathematical model of the
      modular biochemical network of macrophages involved with activation, pathogen
      killing and iron regulation. This model requires synergistic interaction of
      multiple activation signals to overcome the quiescent state. To achieve a trade
      off between macrophage quiescence and activation, strong activation signals are
      modulated via negative regulation by NO. In this way a single activation signal
      is insufficient for complete activation. In addition, our results suggest that
      iron regulation is usually controlled by activation signals. However, under
      conditions of partial macrophage activation, exogenous iron levels play a key
      role in regulating NO production. This model will be useful for evaluating
      macrophage control of intracellular pathogens in addition to the biochemical
      mechanisms examined here.

PMID- 16460765
TI  - Modulation of Na, K-ATPase activity by prostaglandin E1 and [D-Ala2,N-Me
      Phe4,Gly5-ol]-enkephalin.
AB  - Adenylyl cyclase is activated by prostaglandin E and inhibited by mu-opioids.
      Since cAMP-related events influence the activity of the Na Pump and its
      biochemical correlate Na,K-ATPase in many systems, we tested the hypothesis that
      prostaglandin E1 and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), a mu-opioid
      agonist, have opposing actions on Na,K-ATPase activity. Studies were conducted
      with alamethicin-permeabilized SH-SY5Y human neuroblastoma cells. Prostaglandin
      E1 (1 microM) transiently inhibited Na,K-ATPase activity for 10-15 min. A direct
      activator of protein kinase A, 8-Br-cAMP (150 and 500 microM), also inhibited,
      but more rapidly and for a shorter duration. Both DAMGO (1 microM) and Rp
      adenosine 3',5'-cyclic monophosphorothioate (500 microM), a protein kinase A
      inhibitor, reversed the inhibitory effect of prostaglandin E1. DAMGO alone (1
      microM) stimulated Na,K-ATPase activity up to nearly three-fold control activity.
      The stimulatory action of DAMGO was blocked by cyclosporine A (2 microM), an
      inhibitor of calcineurin, and was dependent on Ca2+ entry through nifedipine
      sensitive Ca2+ channels. In the presence of 1 mM EGTA, DAMGO inhibited Na,K
      ATPase activity. DAMGO-induced inhibition was blocked by the inositol 1,4,5
      trisphosphate receptor antagonist xestospongin C (1 microM). Na,K-ATPase is
      poised to modulate neuronal excitability through its roles in maintaining the
      membrane potential and transmembrane ion gradients. The differential effects of
      prostaglandin E1 and opioids on Na,K-ATPase activity may be related to their
      actions in hyperalgesia.

PMID- 16460766
TI  - Applications of LC-MS in the study of the uptake, distribution, metabolism and
      excretion of bioactive polyphenols from dietary supplements.
AB  - Specific and quantitative analyses of the bioactive components and their
      metabolites in body fluids are essential to assess the interaction between groups
      of compounds in dietary supplements and preparations of psychoactives. Reverse
      phase LC separations combined with tandem mass spectrometry provide the necessary
      specificity and sensitivity. In this paper, applications of these methods are
      described for the analysis of isoflavones, salvinorin A, synephrine isomers and
      their metabolites in serum, urine and aqueous humor.

PMID- 16460767
TI  - Effects of mood stabilizers on hippocampus BDNF levels in an animal model of
      mania.
AB  - There is an emerging body of data suggesting that mood disorders are associated
      with decreased brain-derived neurotrophic factor (BDNF). The present study aims
      to investigate the effects of the mood stabilizers lithium (Li) and valproate
      (VPT) in an animal model of bipolar disorder. In the first experiment (acute
      treatment), rats were administered D-amphetamine (AMPH) or saline for 14 days,
      and then between day 8 and 14, rats were treated with either Li, VPT or saline.
      In the second experiment (maintenance treatment), rats were pretreated with Li,
      VPT or saline, and then between day 8 and 14, rats were administered AMPH or
      saline. In both experiments, locomotor activity was measured using the open-field
      test and BDNF levels were measured in rat hippocampus by sandwich-ELISA. Li and
      VPT reversed AMPH-induced behavioral effects in the open-field test in both
      experiments. In the first experiment, Li increased BDNF levels in rat
      hippocampus. In the second experiment, AMPH decreased BDNF levels and Li and VPT
      increased BDNF levels in rat hippocampus. Our results suggest that the present
      model fulfills adequate face, construct and predictive validity as an animal
      model of mania.

PMID- 16460768
TI  - Measurements of metaphase and interphase chromosome aberrations transmitted
      through early cell replication rounds in human lymphocytes exposed to low-LET
      protons and high-LET 12C ions.
AB  - Inheritable chromosome aberrations (CA) are of concern because cytogenetic damage
      may trigger the carcinogenic process. Moreover, stability of radiation-induced CA
      is a prerequisite for meaningful biological dosimetry. CA inheritability arguably
      depends on the aberration structure, with symmetrical exchanges being favoured
      over asymmetrical rearrangements, but it is also affected by radiation quality.
      CA induced by low-LET protons and high-LET 12C ions in G0 peripheral blood
      lymphocytes were measured in first- , second- and third-generation by combined
      FISH/harlequin staining of metaphase as well as prematurely condensed interphase
      chromosomes 1 and 2. As expected, the frequency of non-transmissible (NT)
      aberrations declined through replication rounds. A radiation-induced arrest
      occurred prior to first post-irradiation mitosis that prevalently affected
      aberrant cells. Aberrant cells incurred cycle delays also at subsequent cycles
      following proton-irradiation but not 12C ion-irradiation. As expected, the
      frequency of reciprocal translocations remained fairly stable while that of
      dicentrics was halved at each mitotic round. A significant fraction of complex
      type exchanges was found in third-generation cells following both irradiations
      and appeared to be transmitted relatively more efficiently after protons than 12C
      ions. A low but stably transmitted frequency of transmissible (T)-type insertions
      were detected after 12C ions but not after low LET-irradiation. Our data support
      a differential ability by aberrant cells to progress through post-irradiation
      mitoses that is influenced by the aberration burden and radiation quality.

PMID- 16460769
TI  - The locus coeruleus nucleus as a site of action of the antinociceptive and
      behavioral effects of the nicotinic receptor agonist, epibatidine.
AB  - The mechanisms and sites of action of epibatidine-induced antinociception and
      side effects are poorly understood. The present study tested the hypothesis that
      the locus coeruleus is a site of action of epibatidine. Behavioral responses of
      rats to hindpaw formalin injection were compared after direct administration of
      epibatidine into the locus coeruleus (LC), and after subcutaneous administration.
      Different groups of rats were injected with formalin into the rear paw after
      administration of either ACSF, epibatidine (0.01, 0.06, 0.12, and 0.3mug) into
      the locus coeruleus or epibatidine (2.5-5mug/kg) subcutaneously. Assessment of
      pain-related behavior was done by evaluating the incidence of favoring, lifting
      and licking of the injected paw in the different groups. Abnormal motor behavior
      was also recorded. Infusion of epibatidine into LC induced analgesia, which was
      reversed by prior infusion of mecamylamine into LC. Epibatidine into the locus
      coeruleus resulted in a significant lower pain score in the second phase of the
      formalin test compared to control rats and was as effective as subcutaneous
      epibatidine. The analgesic effects of epibatidine were regionally selective in
      that the administration of epibatidine outside the locus coeruleus area was not
      analgesic. The every tested dose of epibatidine administered into the locus
      coeruleus also produced freezing behavior immediately after injection, which was
      relatively short-lived compared to the analgesic effect. Freezing was inhibited
      by administration of mecamylamine into the LC. Together the results implicate the
      LC as a target for the analgesic effects of epibatidine.

PMID- 16460770
TI  - Abietane diterpenoid dimers from the roots of Salvia prionitis.
AB  - Three abietane diterpenoid dimers, bisprioterones A-C (1-3), were isolated from
      roots of the Chinese folk medicinal plant Salvia prionitis Hance (Labiatae).
      Compounds 1-3 possessed two different abietane diterpenoid skeleta, which were
      linked via either a C-C single bond (1 and 2) or an ether bridge (3). Their
      structures were elucidated by analysis of 1D and 2D NMR spectroscopic data. The
      structure of 1 was further confirmed by a single-crystal X-ray diffraction
      determination.

PMID- 16460771
TI  - N3 potentials in response to high intensity auditory stimuli in animals with
      suspected cochleo-saccular deafness.
AB  - We describe a previously un-reported vertex-negative potential evoked by high
      intensity click auditory stimuli in some dogs and cats with suspected cochleo
      saccular deafness. Brainstem auditory evoked potential tracings from 24
      unilaterally or bilaterally deaf animals, 22 dogs and 2 cats, among which 21
      belonged to breeds with high prevalence of suspected or histologically confirmed
      cochleo-saccular deafness, were studied retrospectively. Values for latency,
      amplitude and threshold of this potential in dogs were 2.15+/-0.23 ms, 0.49+/
      0.25 microV, and 91.9+/-4.7 dB NHL, respectively (mean+/-SD). Latency and
      threshold values in cats were in the mean+/-2 SD range of the dog values.
      Sensitivity to click stimulus polarity and to click stimulus delivery rate
      pointed towards a neural potential instead of a receptor potential. The vertex
      negative wave observed in these animals shares all characteristics with the N3
      potential described in some deaf humans with cochlear deafness, where it is
      presumed to arise from saccular stimulation. The combined degeneration of cochlea
      and sacculus usually reported in deaf white dogs and cats suggest that N3 may
      have a different origin in these species.

PMID- 16460772
TI  - Unifying evolutionary dynamics: from individual stochastic processes to
      macroscopic models.
AB  - A distinctive signature of living systems is Darwinian evolution, that is, a
      propensity to generate as well as self-select individual diversity. To capture
      this essential feature of life while describing the dynamics of populations,
      mathematical models must be rooted in the microscopic, stochastic description of
      discrete individuals characterized by one or several adaptive traits and
      interacting with each other. The simplest models assume asexual reproduction and
      haploid genetics: an offspring usually inherits the trait values of her
      progenitor, except when a mutation causes the offspring to take a mutation step
      to new trait values; selection follows from ecological interactions among
      individuals. Here we present a rigorous construction of the microscopic
      population process that captures the probabilistic dynamics over continuous time
      of birth, mutation, and death, as influenced by the trait values of each
      individual, and interactions between individuals. A by-product of this formal
      construction is a general algorithm for efficient numerical simulation of the
      individual-level model. Once the microscopic process is in place, we derive
      different macroscopic models of adaptive evolution. These models differ in the
      renormalization they assume, i.e. in the limits taken, in specific orders, on
      population size, mutation rate, mutation step, while rescaling time accordingly.
      The macroscopic models also differ in their mathematical nature: deterministic,
      in the form of ordinary, integro-, or partial differential equations, or
      probabilistic, like stochastic partial differential equations or superprocesses.
      These models include extensions of Kimura's equation (and of its approximation
      for small mutation effects) to frequency- and density-dependent selection. A
      novel class of macroscopic models obtains when assuming that individual birth and
      death occur on a short timescale compared with the timescale of typical
      population growth. On a timescale of very rare mutations, we establish rigorously
      the models of "trait substitution sequences" and their approximation known as the
      "canonical equation of adaptive dynamics". We extend these models to account for
      mutation bias and random drift between multiple evolutionary attractors. The
      renormalization approach used in this study also opens promising avenues to study
      and predict patterns of life-history allometries, thereby bridging individual
      physiology, genetic variation, and ecological interactions in a common
      evolutionary framework.

PMID- 16460773
TI  - Major carcinogenic pathways identified by gene expression analysis of peritoneal
      mesotheliomas following chemical treatment in F344 rats.
AB  - This study was performed to characterize the gene expression profile and to
      identify the major carcinogenic pathways involved in rat peritoneal mesothelioma
      (RPM) formation following treatment of Fischer 344 rats with o-nitrotoluene (o
      NT) or bromochloracetic acid (BCA). Oligo arrays, with over 20,000 target genes,
      were used to evaluate o-NT- and BCA-induced RPMs, when compared to a non
      transformed mesothelial cell line (Fred-PE). Analysis using Ingenuity Pathway
      Analysis software revealed 169 cancer-related genes that were categorized into
      binding activity, growth and proliferation, cell cycle progression, apoptosis,
      and invasion and metastasis. The microarray data were validated by positive
      correlation with quantitative real-time RT-PCR on 16 selected genes including
      igf1, tgfb3 and nov. Important carcinogenic pathways involved in RPM formation
      included insulin-like growth factor 1 (IGF-1), p38 MAPkinase, Wnt/beta-catenin
      and integrin signaling pathways. This study demonstrated that mesotheliomas in
      rats exposed to o-NT- and BCA were similar to mesotheliomas in humans, at least
      at the cellular and molecular level.

PMID- 16460774
TI  - 'Venomics' or : The venomous systems genome project.

PMID- 16460775
TI  - A mature and fusogenic form of the Nipah virus fusion protein requires
      proteolytic processing by cathepsin L.
AB  - The Nipah virus fusion (F) protein is proteolytically processed to F1 + F2
      subunits. We demonstrate here that cathepsin L is involved in this important
      maturation event. Cathepsin inhibitors ablated cleavage of Nipah F. Proteolytic
      processing of Nipah F and fusion activity was dramatically reduced in cathepsin L
      shRNA-expressing Vero cells. Additionally, Nipah virus F-mediated fusion was
      inhibited in cathepsin L-deficient cells, but coexpression of cathepsin L
      restored fusion activity. Both purified cathepsin L and B could cleave
      immunopurified Nipah F protein, but only cathepsin L produced products of the
      correct size. Our results suggest that endosomal cathepsins can cleave Nipah F,
      but that cathepsin L specifically converts Nipah F to a mature and fusogenic
      form.

PMID- 16460776
TI  - Immunization of rhesus macaques with a polyvalent DNA prime/protein boost human
      immunodeficiency virus type 1 vaccine elicits protective antibody response
      against simian human immunodeficiency virus of R5 phenotype.
AB  - The immunogenicity of a poylvalent HIV-1 vaccine comprised of Env antigens from
      primary R5 isolates was evaluated in rhesus macaques. DNA vaccines encoding four
      Env antigens from multiple HIV-1 subtypes and HIV-1 Gag antigen from a single
      subtype elicited a persistent level of binding antibodies to gp120 from multiple
      HIV-1 isolates that were markedly enhanced following boosting with homologous
      gp120 proteins in QS-21 adjuvant irrespective of the route of DNA immunization.
      These sera neutralized homologous and, to a lesser degree, heterologous HIV-1
      isolates. Four of the six immunized animals were completely protected following
      rectal challenge with a SHIV encoding Env from HIV-1(Ba-L), whereas the virus
      load was reduced in the remaining animals compared to naive controls. Hence
      priming with DNA encoding Env antigens from multiple HIV-1 clades followed by
      boosting with homologous Env proteins elicits anti-HIV-1 immune responses capable
      of protecting macaques against mucosal transmission of R5 tropic SHIV isolate.

PMID- 16460777
TI  - Induction of productive human papillomavirus type 11 life cycle in epithelial
      cells grown in organotypic raft cultures.
AB  - The study of the human papillomavirus (HPV) life cycle was hampered for more than
      50 years by the lack of a conventional cell culture system for propagating HPV.
      Considerable progress has been made in the production of several HPV types using
      either organotypic rafts or human epithelial xenografts in immunocompromised
      mice. In this study, we demonstrated episomal maintenance of HPV-11 DNA in N-Tert
      cells. HPV-11 episomal DNA containing cell populations grown in raft culture
      showed induction of the productive viral life cycle. HPV-11 DNA amplification and
      viral capsid antigen synthesis were detected in differentiated layers of
      epithelia. The viruses generated were able to infect keratinocytes in vitro,
      which indicate that viruses generated were infectious. The demonstration of the
      productive HPV-11 life cycle in raft culture from cloned HPV-11 DNA will
      facilitate genetic analyses of viral gene functions that was not possible using
      the human xenograft athymic mouse model.

PMID- 16460778
TI  - Comparative analysis of the antiretroviral activity of APOBEC3G and APOBEC3F from
      primates.
AB  - APOBEC3G and APOBEC3F exhibit antiretroviral activity primarily as a consequence
      of their ability to deaminate cytidines in retroviral DNA. Here, we compare the
      properties of APOBEC3F and APOBEC3G from human, macaque, and African green monkey
      (AGM). While all APOBEC proteins tested exhibited anti-HIV-1 activity, human
      APOBEC3F was, surprisingly, 10- to 50-fold less potent than human APOBEC3G.
      However, similar discrepancies in antiviral potency were not found when pairs of
      proteins from macaque and AGM were compared. Intrinsic differences in the ability
      of each APOBEC protein to induce hypermutation, rather than differences in
      packaging efficiency, partially accounted for variable antiretroviral activity.
      Each of four primate lentivirus Vif proteins reduced human and AGM APOBEC3F
      expression and antiviral activity, but all were only partially effective and
      species-specific effects were relatively minor. Overall, highly efficient and
      species-specific neutralization of APOBEC3G, and less efficient neutralization of
      APOBEC3F, appears to be a general property of Vif proteins.

PMID- 16460779
TI  - Effect of UTP sugar and base modifications on vaccinia virus early gene
      transcription.
AB  - Prior efforts demonstrated that RNA oligonucleotides containing the transcription
      termination signal UUUUUNU stimulate premature termination of vaccinia virus
      early gene transcription, in vitro. This observation suggests that viral
      transcription termination may be an attractive target for the development of anti
      poxvirus agents. Since short RNA molecules are readily susceptible to nuclease
      digestion, their use would require stabilizing modifications. In order to
      evaluate the effect of both ribose and uracil modifications of the U5NU signal on
      early gene transcription termination, UTP derivatives harboring modifications to
      the uracil base, the 2' position of the ribose sugar and the phosphodiester bond
      were examined in an in vitro vaccinia virus early gene transcription termination
      system. Incorporation of 4-S-U, 5-methyl-U, 2-S-U, pseudo U and 2'-F-dU into the
      nascent transcript inhibited transcription termination. 6-aza-U, 2'-amino-U, 2'
      azido-U and 2'-O methyl-U inhibited transcription elongation resulting in the
      accumulation of short transcripts. The majority of the short transcripts remained
      in the ternary complex and could be chased into full-length transcripts.
      Initially, derivatives of all uridines in the termination signal were tested.
      Partial modification of the termination signal reduced termination activity, as
      well. Introduction of 2'-O methyl ribose to the first three uridines of the U9
      termination signal reduced the ability of U9 containing oligonucleotides to
      stimulate in vitro transcription termination, in trans. Further modifications
      eliminated this activity. Thus, viral early gene transcription termination
      demonstrates a rigorous requirement for a U5NU signal that is unable to tolerate
      modification to the base or sugar. Additionally, VTF was shown to enhance
      transcription elongation through the T9 sequence in the template. These results
      suggest that VTF may play a subtle role in early gene transcription elongation in
      addition to its known function in mRNA cap formation, early gene transcription
      termination and intermediate gene transcription initiation.

PMID- 16460780
TI  - Long-term analysis of a full-scale activated sludge wastewater treatment system
      exhibiting seasonal biological foaming.
AB  - The seasonal accumulation of biological foam on the activated sludge system of
      the Urbana-Champaign Sanitary District Northeast (UCSD-NE) wastewater treatment
      plant was investigated over an 8-year period by statistical analyses including
      path analysis, multivariate regression, and principal component analysis. Results
      of these analyses suggested that variation in the activated sludge reactor
      temperature and the use of a stream bypassing the primary clarifier were the two
      main factors determining the observed temporal foam profile. Characterization of
      the primary clarifier influent and effluent suggested the involvement of high
      lipid loading rates from the bypass stream in foam accumulation. In light of
      these results, it is hypothesized that increasing temperatures and lipid loading
      rates are responsible for foam formation through the same mechanism: the foam
      forming microbial population is specialized in consuming lipids, substrates
      classified as slowly degradable. When the temperature increases, the rate of
      lipid hydrolysis becomes sufficiently high for this population to become
      abundant, accumulate on the surfaces of the aeration basins, and cause biological
      foaming.

PMID- 16460781
TI  - Effect of nitrite concentration on the distribution and competition of nitrite
      oxidizing bacteria in nitratation reactor systems and their kinetic
      characteristics.
AB  - Genus Nitrospira and Nitrobacter species are the key nitrite-oxidizing bacteria
      (NOB) in nitrifying wastewater treatment plants. It has been hypothesized that
      genus Nitrospira are K-strategists and can exploit low amounts of nitrite more
      efficiently than Nitrobacter. In contrast, Nitrobacter species are r-strategists
      that can grow faster than Nitrospira. To elucidate the K/r hypothesis and to
      analyze the effect of substrate (nitrite) concentration on the competition and
      distribution of the two NOB, two different reactor types were employed for
      nitrite oxidation (nitratation) and NOB growth. The continuous biofilm airlift
      reactor (CBAR) maintained low nitrite concentration due to the complete oxidation
      of nitrite in continuous operation while the sequencing batch reactor (SBR) was
      kept in a relatively high nitrite concentration environment due to a cyclic
      substrate concentration profile. Fluorescence in situ hybridization (FISH) and
      confocal laser scanning microscopy (CLSM) showed that both Nitrobacter species
      and genus Nitrospira were present in the CBAR and the SBR. Quantitative FISH
      analyses of the CBAR showed that Nitrospira occupied 59% of the total bacteria
      while Nitrobacter occupied only 5%. On the other hand, Nitrobacter, occupying
      64%, was the dominant NOB in the SBR, and only 3% of total bacteria belonged to
      genus Nitrospira. Nitrite oxidation kinetics and quantitative FISH analyses
      revealed that the specific nitrite oxidation activities of Nitrobacter and
      Nitrospira are 93.8 and 10.5 mg/g NOB h, respectively, and the specific activity
      of Nitrobacter is about 9 times higher than that of Nitrospira. In conclusion,
      the results confirm the K/r hypothesis and the distribution of Nitrobacter and
      Nitrospira is likely to depend mainly on nitrite concentration. It seems that
      nitrite load and starvation conditions do not give a direct effect on the
      distribution of NOB.

PMID- 16460782
TI  - Removal of atrazine, lindane and diazinone from water by organo-zeolites.
AB  - Systematic adsorption tests were carried out to determine the efficiency of
      organo-zeolite (OZ) for removal of atrazine, lindane and diazinone from water.
      The hydrophobic character of OZ-pesticide interactions was confirmed by measuring
      the amount of pesticides sorbed on zeolite samples modified with 25, 50, 75 and
      150 mmol of stearyldimethylbenzylammoniumchloride (SDBAC)/kg of zeolite. The
      effects of adsorbent particle size, solid content in the suspension and the
      initial pesticide concentration in the solutions were also investigated. For
      effective adsorption of diazinone onto an OZ, it is necessary for the
      SDBAC/diazinon ratio to be higher than 25. The adsorption capacities, calculated
      by fitting the experimental data to the Langmuir-Freundlich equation, were 2.0
      micromol/g (atrazine), 4.4 micromol/g (diazinone) and 3.4 micromol/g (lindan). At
      lower initial concentrations of pesticide solution, a linear dependence existed
      between the amount adsorbed and the equilibrium concentration of pesticide.
      Column experiments showed that at volumetric flow of 6 cm3/ min, the breakthrough
      points (at C/C0 = 0.1) were 560 bed volume (BV) for lindane and 620 for
      diazinone.

PMID- 16460783
TI  - Erythrocyte glycohydrolases in subjects with trisomy 21: could Down's syndrome be
      a model of accelerated ageing?
AB  - We studied some erythrocyte glycohydrolases, erythrocyte membrane fluidity,
      plasma hydroperoxides and total antioxidant defences in 23 Down syndrome (DS)
      individuals in comparison with healthy age-matched and elderly controls. With
      regard to erythrocyte plasma membrane fluidity, plasma hydroperoxides and total
      plasma oxidative defences, DS subjects resembled the age-matched controls more
      than the elderly ones. Membrane glycohydrolases in DS, however, presented a
      pattern partly similar to age-matched controls and partly to elderly controls.
      Concerning cytosol glycohydrolases, DS subjects had lower levels of
      hexosaminidase and N-acetyl-beta-D-glucosaminidase, the latter specific for the
      hydrolysis of GlcNAc residues O-linked to proteins. In general, erythrocyte
      membrane and cytosol glycohydrolases decreased during erythrocyte ageing in DS
      subjects and in all controls. The increased levels of the same enzymes in DS
      plasma might be attributed to an alteration of their release-uptake mechanisms
      between the two different compartments, on account of the higher plasma
      hydroperoxide levels. These findings indicate that erythrocyte ageing in DS
      differs partially from that of age-matched and elderly controls. In any case, the
      accelerated ageing seen in DS is no fully comparable to physiological ageing.

PMID- 16460784
TI  - Application of artificial neural networks to assess pesticide contamination in
      shallow groundwater.
AB  - In this study, a feed-forward back-propagation neural network (BPNN) was
      developed and applied to predict pesticide concentrations in groundwater
      monitoring wells. Pesticide concentration data are challenging to analyze because
      they tend to be highly censored. Input data to the neural network included the
      categorical indices of depth to aquifer material, pesticide leaching class,
      aquifer sensitivity to pesticide contamination, time (month) of sample
      collection, well depth, depth to water from land surface, and additional travel
      distance in the saturated zone (i.e., distance from land surface to midpoint of
      well screen). The output of the neural network was the total pesticide
      concentration detected in the well. The model prediction results produced good
      agreements with observed data in terms of correlation coefficient (R=0.87) and
      pesticide detection efficiency (E=89%), as well as good match between the
      observed and predicted "class" groups. The relative importance of input
      parameters to pesticide occurrence in groundwater was examined in terms of R, E,
      mean error (ME), root mean square error (RMSE), and pesticide occurrence "class"
      groups by eliminating some key input parameters to the model. Well depth and time
      of sample collection were the most sensitive input parameters for predicting the
      pesticide contamination potential of a well. This infers that wells tapping
      shallow aquifers are more vulnerable to pesticide contamination than those wells
      tapping deeper aquifers. Pesticide occurrences during post-application months
      (June through October) were found to be 2.5 to 3 times higher than pesticide
      occurrences during other months (November through April). The BPNN was used to
      rank the input parameters with highest potential to contaminate groundwater,
      including two original and five ancillary parameters. The two original parameters
      are depth to aquifer material and pesticide leaching class. When these two
      parameters were the only input parameters for the BPNN, they were not able to
      predict contamination potential. However, when they were used with other
      parameters, the predictive performance efficiency of the BPNN in terms of R, E,
      ME, RMSE, and pesticide occurrence "class" groups increased. Ancillary data
      include data collected during the study such as well depth and time of sample
      collection. The BPNN indicated that the ancillary data had more predictive power
      than the original data. The BPNN results will help researchers identify
      parameters to improve maps of aquifer sensitivity to pesticide contamination.

PMID- 16460785
TI  - Turbidity dynamics during spring storm events in an urban headwater river system:
      the Upper Tame, West Midlands, UK.
AB  - Turbidity is an important water quality variable, through its relation to light
      suppression, BOD impact, sediment-associated contaminant transport, and suspended
      sediment effects on organisms and habitats. Yet few published field
      investigations of wet-weather turbidity dynamics, through several individual and
      sequenced rainstorms in extremely urbanised headwater basins, have emerged. This
      paper aims to address this gap through a turbidity analysis of multiple storm
      events in spring 2001 in an urban headwater basin (57 km2) of the River Tame,
      central England, the most urbanised basin for its size in the UK ( approximately
      42%). Data were collected at 15-min frequency at automated monitoring stations
      for rainfall, streamflow and six water quality variables (turbidity, EC,
      temperature, DO, pH, ammonia). Disturbance experiments also allowed estimates of
      bed sediment storage to be obtained. Six important and unusual features of the
      storm event turbidity response were apparent: (1) sluggish early turbidity
      response, followed by a turbidity 'rush'; (2) quasi-coincident flow and turbidity
      peaks; (3) anti-clockwise hysteresis in the discharge-turbidity relationship on
      all but one event, resulting from Falling-LImb Turbidity Extensions (FLITEs); (4)
      increases in peak turbidity levels through storm sequences; (5) initial micro
      pulses (IMP) in turbidity; and (6) secondary turbidity peaks (STP) or 'turbidity
      shoulders' (TS). These features provided very little evidence of a true 'first
      flush' effect: instead, substantial suspended solids transport continued right
      through the flow recessions, and little storm-event sediment exhaustion was
      evident. A new, dimensionless, hysteresis index, HI(mid), is developed to
      quantify the magnitude and direction of hysteresis in a simple, clear, direct and
      intuitive manner. This allowed the degree of departure from the classic 'first
      flush', clockwise hysteresis models to be assessed. Of the 15 turbidity events
      considered, 10 coincided with ammonia spikes of up to 6.25 mg l(-1) at Water
      Orton (the downstream station): this suggests that spills from combined sewer
      overflows (CSO) or waste water treatment works (WwTWs) are significant in the
      throughput of turbid waters here. Substantial ammonia peaks related most strongly
      to total storm rainfall receipt, of four rainfall variables considered, and
      significant ammonia peaks were generated even from low-magnitude storms (rainfall
      totals <4 mm), indicating that spills are a frequent occurrence. Local bed
      sediment stores appear to be limited, suggesting that other distal sediment
      sources, such as road networks and old mineworkings are possibly more important.
      Biofilms may also play a part in delaying sediment release until late in the
      hydrograph, and in suppressing late spring turbidity levels. Existing first-flush
      models appear to be an oversimplification here. Such urban headwater basin
      responses can provide useful insights into the generation of contaminant waves,
      and offer vital early-warning systems for pollution events propagating
      downstream.

PMID- 16460786
TI  - Incidence of deep vein thrombosis in hospitalized Chinese medical patients is
      similar to that in western populations.

PMID- 16460787
TI  - The role of maintenance therapy and novel taxanes in ovarian cancer.
AB  - OBJECTIVES: Despite several studies reporting various degrees of success, the
      role of maintenance chemotherapy in ovarian cancer remains controversial. This
      article reviews the available data and the controversy surrounding maintenance
      therapy. In addition, the role of novel taxanes, which may offer an improved
      therapeutic index and reduced toxicity relative to conventional therapies in this
      setting, is discussed. METHODS: The available randomized clinical data on
      extended or maintenance therapy in ovarian cancer are reviewed. RESULTS:
      Available data indicate that patients with ovarian cancer undergoing taxane
      maintenance chemotherapy exhibit a reduced recurrence rate and a longer
      progression-free survival. CONCLUSIONS: While an additional randomized trial is
      needed to confirm these benefits and establish maintenance therapy as the
      standard of care, the authors conclude that maintenance therapy is a valuable
      option that should be discussed with patients until further data are available.
      The Gynecologic Oncology Group 212 trial is a randomized clinical trial that is
      designed to answer whether taxane maintenance therapy offers a survival advantage
      as well as to determine the impact of such a therapeutic regimen on a patient's
      quality of life. This trial is also designed to address some of the questions
      regarding the role of a novel taxane in maintenance therapy in ovarian cancer.

PMID- 16460788
TI  - Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and
      rats.
AB  - Few studies have examined the effects of 5-methoxy-N,N-diisopropyltryptamine (5
      MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited
      head twitch assay in mice where it was compared to the structurally similar
      hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective
      serotonin (5-HT)2A antagonist M100907, and in a lysergic acid diethylamide (LSD)
      discrimination assay in rats where its subjective effects were challenged with
      M100907 or the 5-HT 1A selective antagonist WAY-100635. Finally, the affinity of
      5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO
      DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this
      effect was potently antagonized by prior administration of M100907. In rats
      trained with LSD as a discriminative stimulus, there was an intermediate degree
      (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of
      response rates. These interoceptive effects were abolished by M100907, but were
      not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar
      affinity for 5-HT 2A and 5-HT 2C receptors, but much higher affinity for 5-HT 1A
      receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist
      activity, and has affinity at receptors relevant to hallucinogen effects. The
      effectiveness with which M100907 antagonizes the behavioral actions of this
      compound, coupled with the lack of significant antagonist effects of WAY-100635,
      strongly suggests that the 5-HT 2A receptor is an important site of action for 5
      MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT 1A receptor.

PMID- 16460789
TI  - Cardiovascular disease knowledge among culturally Deaf patients in Chicago.
AB  - BACKGROUND: Deaf persons experience communication barriers that may impact on
      their knowledge of cardiovascular disease (CVD); however, data measuring this
      deficit are limited. A comprehensive health survey of Deaf adults included
      questions on CVD knowledge. METHODS: Between November 2002 and March 2003, 203
      Deaf adults participated in the survey, which was conducted via face-to-face
      interviews in American Sign Language. Questions assessed knowledge of heart
      attack and stroke symptoms, risk factors, and emergency response. RESULTS: Forty
      percent of respondents could not list any symptoms of a heart attack, while over
      60% could not list any symptoms of a stroke. Less than half of respondents
      identified chest pain/pressure as a symptom of a heart attack. Only 61% reported
      that they would call 911 in response to cardiovascular disease symptoms. The
      median number of risk factors correctly identified by respondents was 3 of 6.
      CONCLUSIONS: Knowledge of cardiovascular disease among Deaf respondents is low,
      and considerably lower than that of the general hearing population. The need to
      develop health education materials and programs for Deaf individuals is evident.
      Health care providers should be educated on Deaf culture and barriers in
      communication. Finally, efforts need to be made to assure that 911 is deaf
      accessible.

PMID- 16460790
TI  - Comparative endocrine investigations in three bear species based on urinary
      steroid metabolites and volatiles.
AB  - In order to improve breeding of in situ populations of bears, a comprehensive
      study of reproductive physiology in Brown (Ursus arctos), Spectacled (Tremarctos
      ornatus) and Giant panda bears (Ailuropoda melanoleuca) was performed. The
      objective was to perform non-invasive analyses of urinary and fecal steroid
      metabolites. In addition, we investigated the presence of reproduction-related
      urinary volatile substances of these bears that might trigger the reproductive
      behavior. Urinary estrogen concentrations, routinely used to monitor follicular
      activity in Giant panda, were inappropriate for monitoring follicular activity in
      Spectacled bear. In addition, no estrogen peak related to mating activity was
      observed in Brown bear. Further contrasting Giant panda, although urinary
      pregnanediol analyses failed to indicate luteal activity in either Spectacled or
      Brown bears, urinary (Spectacled bear) and fecal (Brown bear) concentrations of
      progesterone were an appropriate indicator of luteal activity. The Giant panda
      had volatile components (medium-chain fatty acids) in their urine that increased
      simultaneously with the seasonal increase of estrogens. These fatty acids were
      also detected in the Brown during estrus and Spectacled bear. Further studies on
      the behavioral relevance of these fatty acids are required to determine if they
      are pheromones.

PMID- 16460791
TI  - Effects of grammatical categories on children's visual language processing:
      Evidence from event-related brain potentials.
AB  - This study examined how school-aged children process different grammatical
      categories. Event-related brain potentials elicited by words in visually
      presented sentences were analyzed according to seven grammatical categories with
      naturally varying characteristics of linguistic functions, semantic features, and
      quantitative attributes of length and frequency. The categories included nouns,
      adjectives, verbs, pronouns, conjunctions, prepositions, and articles. The
      findings indicate that by the age of 9-10 years, children exhibit robust neural
      indicators differentiating grammatical categories; however, it is also evident
      that development of language processing is not yet adult-like at this age. The
      current findings are consistent with the hypothesis that for beginning readers a
      variety of cues and characteristics interact to affect processing of different
      grammatical categories and indicate the need to take into account linguistic
      functions, prosodic salience, and grammatical complexity as they relate to the
      development of language abilities.

PMID- 16460792
TI  - Prosodic processing by children: an fMRI study.
AB  - Prosodic information in the speech signal carries information about linguistic
      structure as well as emotional content. Although children are known to use
      prosodic information from infancy onward to assist linguistic decoding, the brain
      correlates of this skill in childhood have not yet been the subject of study.
      Brain activation associated with processing of linguistic prosody was examined in
      a study of 284 normally developing children between the ages of 5 and 18 years.
      Children listened to low-pass filtered sentences and were asked to detect those
      that matched a target sentence. fMRI scanning revealed multiple regions of
      activation that predicted behavioral performance, independent of age-related
      changes in activation. Likewise, age-related changes in task activation were
      found that were independent of differences in task accuracy. The overall pattern
      of activation is interpreted in light of task demands and factors that may
      underlie age-related changes in task performance.

PMID- 16460793
TI  - Temporal processing and context dependency of phoneme discrimination in patients
      with aphasia.
AB  - Standard diagnostic procedures for assessing temporal-processing abilities of
      adult patients with aphasia have so far not been developed. In our study,
      temporal-order measurements were conducted using two different experimental
      procedures to identify a suitable measure for clinical studies. Additionally,
      phoneme-discrimination abilities were tested on the word, as well as on the
      sentence level, as a relationship between temporal processing and phoneme
      discrimination abilities is assumed. Patients with aphasia displayed
      significantly higher temporal-order thresholds than control subjects. The
      detection of an association between temporal processing and speech processing,
      however, depended on the stimuli and the phoneme-discrimination tasks used. Our
      results also suggest top-down feedback on phonemic processing.

PMID- 16460794
TI  - The real-time polymerase chain reaction.
AB  - The scientific, medical, and diagnostic communities have been presented the most
      powerful tool for quantitative nucleic acids analysis: real-time PCR [Bustin,
      S.A., 2004. A-Z of Quantitative PCR. IUL Press, San Diego, CA]. This new
      technique is a refinement of the original Polymerase Chain Reaction (PCR)
      developed by Kary Mullis and coworkers in the mid 80:ies [Saiki, R.K., et al.,
      1985. Enzymatic amplification of beta-globin genomic sequences and restriction
      site analysis for diagnosis of sickle cell anemia, Science 230, 1350], for which
      Kary Mullis was awarded the 1993 year's Nobel prize in Chemistry. By PCR
      essentially any nucleic acid sequence present in a complex sample can be
      amplified in a cyclic process to generate a large number of identical copies that
      can readily be analyzed. This made it possible, for example, to manipulate DNA
      for cloning purposes, genetic engineering, and sequencing. But as an analytical
      technique the original PCR method had some serious limitations. By first
      amplifying the DNA sequence and then analyzing the product, quantification was
      exceedingly difficult since the PCR gave rise to essentially the same amount of
      product independently of the initial amount of DNA template molecules that were
      present. This limitation was resolved in 1992 by the development of real-time PCR
      by Higuchi et al. [Higuchi, R., Dollinger, G., Walsh, P.S., Griffith, R., 1992.
      Simultaneous amplification and detection of specific DNA-sequences. Bio
      Technology 10(4), 413-417]. In real-time PCR the amount of product formed is
      monitored during the course of the reaction by monitoring the fluorescence of
      dyes or probes introduced into the reaction that is proportional to the amount of
      product formed, and the number of amplification cycles required to obtain a
      particular amount of DNA molecules is registered. Assuming a certain
      amplification efficiency, which typically is close to a doubling of the number of
      molecules per amplification cycle, it is possible to calculate the number of DNA
      molecules of the amplified sequence that were initially present in the sample.
      With the highly efficient detection chemistries, sensitive instrumentation, and
      optimized assays that are available today the number of DNA molecules of a
      particular sequence in a complex sample can be determined with unprecedented
      accuracy and sensitivity sufficient to detect a single molecule. Typical uses of
      real-time PCR include pathogen detection, gene expression analysis, single
      nucleotide polymorphism (SNP) analysis, analysis of chromosome aberrations, and
      most recently also protein detection by real-time immuno PCR.

PMID- 16460795
TI  - Applications of real-time immuno-polymerase chain reaction (rt-IPCR) for the
      rapid diagnoses of viral antigens and pathologic proteins.
AB  - One of the major challenges of performing the IPCR has been to establish a
      robust, sensitive, and specific method which is easily adapted and highly
      standardized for routine use in a clinical laboratory. Presently, the performance
      of IPCR typically involves elaborate and multiple, time-consuming steps prone to
      high variation in reagents and technical application. Further advances in the
      technology and instrumentation used for the signal detection of IPCR has resulted
      in the development of real-time IPCR (rt-IPCR). Rt-IPCR is still relatively
      undeveloped in comparison to the use of both real-time PCR and IPCR as evidenced
      by the low number (eight citations) of publications in the scientific literature.
      However, increased use of rt-IPCR has shown that the method displays improved
      statistical validation of accuracy over IPCR. Inter-assay error is typically 5
      10% vs 15-20% for IPCR. The primary advantage of using rt-IPCR in place of IPCR
      is the immediate interpretation of positive data (quantification of proteins) as
      the PCR reaction proceeds. This aspect is key to real-time diagnosis and has
      great importance for specific emergency situations (i.e., biological and
      environmental contaminations of toxins in biothreat situations), as well as cases
      where specific tumor/viral antigens and pathologic proteins may be present in
      body tissues in extremely low concentrations and rapid, early diagnosis is
      important for immediate palliative treatment. This review summarizes all of the
      experimental data published to date utilizing the rt-IPCR method for various
      analytes (vascular endothelial growth factor, mumps Ag, rViscumin, various IgG,
      gliadin, HIV-1 p24 Ag, Rotavirus VP6, pathologic and recombinant prion, and
      prostate specific Ag) and describes the molecular scaffold formats, solid
      formats, instrument detection systems, and probes/primers or fluorescent dyes
      used in these assays. With further standardization and validation, rt-IPCR has
      the potential to become the most analytically sensitive method available for the
      detection of proteins.

PMID- 16460796
TI  - Glycocalyx-mimetic dextran-modified poly(vinyl amine) surfactant coating reduces
      platelet adhesion on medical-grade polycarbonate surface.
AB  - A dextran-modified poly(vinyl amine) comb-like surfactant polymer, poly(N-vinyl
      dextran aldonamide-co-N-vinyl hexanamide), that can surface-adsorb on hydrophobic
      polymeric substrates, was designed to improve the interfacial blood-compatibility
      of polymeric biomaterials. Medical-grade polycarbonate was selected as a model
      substrate because of its extensive use in blood-contacting biomedical devices
      like hemodialyzers, blood pumps and oxygenators. The surfactant polymer was
      physisorbed from aqueous solution onto the polycarbonate substrate. The
      surfactant coating was stable under dynamic shear conditions in whole blood, as
      confirmed by fluorescence microscopy and total internal reflection fluorescence
      (TIRF) experiments with fluorescein-labeled surfactant polymer. The coated disks
      and uncoated control disks were exposed to platelet-rich plasma (PRP) and whole
      human blood in a rotating disk system (RDS) to study platelet-adhesion under
      dynamic shear stress environments. Adhered platelets were stained with
      fluorescein isothiocyante (FITC)-tagged anti-CD41a monoclonal antibody and imaged
      by epifluorescence microscopy. Complimentary images were obtained by phase
      contrast microscopy. Platelet adhesion on the surfactant-coated disks was reduced
      by approximately 90%, compared with uncoated disks. The images also showed a
      concomitant reduction in platelet-derived microparticles on surfactant-coated
      disks, compared with uncoated disks. The results suggest potential application of
      carbohydrate-modified surfactant polymers as a glycocalyx-mimetic non
      thrombogenic interfacial coating for blood-contacting biomaterials.

PMID- 16460798
TI  - Transport of glyburide by placental ABC transporters: implications in fetal drug
      exposure.
AB  - Much evidence has demonstrated that a number of ATP-binding cassette (ABC) efflux
      transporters including P-glycoprotein (PGP), the multidrug resistance-associated
      proteins (MRPs) and the breast cancer resistance protein (BCRP) are highly
      expressed in placental tissues and are believed to profoundly limit the passage
      of therapeutic or toxic xenobiotics to the fetus. Recent studies indicate that
      the oral hypoglycemic glyburide does not cross the human placenta to an
      appreciable extent. Our objective was to identify placental transporters
      potentially involved in limiting the transplacental transfer of glyburide to the
      fetus. Thus, [(3)H]-glyburide transport was examined in BCRP, PGP, MRP1, MRP2 and
      MRP3 over-expressing cell lines in the presence or absence of specific
      inhibitors. Our results demonstrated significant increases in the intracellular
      accumulation of [(3)H]-glyburide in BCRP and MRP3 over-expressing cells in the
      presence of the inhibitors novobiocin and indomethacin, respectively. PGP
      inhibition with verapamil or MRP inhibition with indomethacin did not affect
      [(3)H]-glyburide accumulation in the PGP or MRP2 over-expressing cell lines and
      only limited changes were seen in the MRP1 over-expressing cell line. On the
      other hand, glyburide was found to significantly inhibit MRP1-, MRP2- and MRP3
      mediated efflux of 5-carboxyfluorescein diacetate and PGP-mediated transport of
      rhodamine 123. Our evidence is the first to clearly indicate that glyburide is
      preferentially transported by BCRP and MRP3.

PMID- 16460797
TI  - Surface-induced changes in protein adsorption and implications for cellular
      phenotypic responses to surface interaction.
AB  - Understanding external factors that determine cellular phenotypic responses is of
      key interest in the field of biomaterials. Currently, material surface
      characteristics, protein adsorption and cellular phenotypic responses are all
      considered to be interrelated and ultimately determine the biocompatibility of
      materials. The exact nature of the relationship between these distinct, yet
      related, phenomena still remains to be elucidated. Through the use of a series of
      thermoresponsive N-isopropylacrylamide-based co-polymer films, we aimed to shed
      light on the relationship between surface hydrophobicity, protein adsorption and
      subsequent cellular response. Despite changes in co-polymer hydrophobicity
      mediated by altered ratios of constituent monomers, differential cellular
      response was only apparent in the presence of serum. Co-polymer films displayed
      alterations with respect to the amount of protein adsorbed on the surface, with
      individual serum proteins (albumin and fibronectin) displaying contrasting
      adsorption characteristics. Changes in protein adsorption corresponded to changes
      in cell adhesion, cytoskeletal organisation and cell morphology, as well as to
      changes in cell movement and intracellular signalling events. Examination of
      focal adhesion kinase (FAK), and extracellular signal-regulated kinase (ERK 1/2),
      important mediators of adhesion and growth factor-related signalling events,
      revealed a comparative reduction in phosphorylation of these signalling proteins
      in cells grown on co-polymers in comparison to those cultured on tissue culture
      polystyrene (TCP; used as a control surface). We also associated surface-mediated
      phenotypic alterations of cells grown on TCP and co-polymer films with particular
      changes in gene expression. These results indicate that cellular response to
      interaction with our series of co-polymer films is determined by the surface
      adsorbed protein layer, which in turn is determined by the changing surface
      chemistry as the ratio of the co-monomers is altered.

PMID- 16460799
TI  - PGE(2) receptor subtype functionality on immature forms of human leukemic blasts.
AB  - The ability of prostaglandin E2 (PGE2) to regulate the immune system is well
      documented. PGE2 effects are mediated through interactions with four distinct
      membrane EP receptors (EP(1-4)). We investigated, for the first time, the
      functionality of EP receptors on immature forms of blast cells of acute myeloid
      leukemic (AML) and acute lymphoid leukemic (ALL) patients. RT-PCR experiments
      documented the presence of the four EP receptor subtype transcripts in leukemic
      blasts of AML M0, AML M1, AML M2 and ALL patients. Western blot analysis only
      documented the presence of the EP2 receptor. Functional assays (cAMP production,
      calcium flux) confirmed Western blot results, i.e., the presence of functional
      EP2 receptors. Results of the present study suggest that the mechanism used by
      PGE2 to influence blast physiology is mediated through the EP2 receptor subtype,
      and subsequently through a cAMP-elevating effect. Results obtained with M0-2
      subtypes have to be necessarily extended to more differentiated phenotype.

PMID- 16460800
TI  - Mutation screening for JAK2V617F: when to order the test and how to interpret the
      results.
AB  - With the application of adequately sensitive tests, it is now becoming evident
      that more than 90% of patients with conventionally-defined polycythemia vera (PV)
      carry the somatic JAK2V617F mutation in their granulocytes. However, the specific
      mutation is also found in other classic and atypical myeloproliferative disorders
      (MPD), albeit at a lesser frequency. In contrast, JAK2V617F has not been reported
      in patients with either reactive myeloproliferation or lymphoid disorders.
      Therefore, mutation screening for JAK2V617F can be considered as a myeloid
      specific clonality assay and it is diagnostically most useful in the evaluation
      of "polycythemia".

PMID- 16460801
TI  - Identification of c-Kit gene mutations in patients with polycythemia vera.
AB  - Imatinib mesylate has recently been reported to have clinical activity in the
      treatment of polycythemia vera (PV), suggesting the involvement of one of the
      kinases targeted by this inhibitor, including c-Kit and PDGFR. Activating c-Kit
      mutations have been identified in patients with mastocytosis and other myeloid
      disorders such as acute myeloid leukemia. Thus, we wanted to analyze the presence
      of mutations of c-Kit in polycythemia vera patients. We found that 7 out of 20
      patients carried missense mutations in the c-Kit gene whereas no sequence
      variation was detected in 15 healthy controls.

PMID- 16460802
TI  - Bullying among Turkish high school students.
AB  - OBJECTIVE: The purpose of this study was to investigate school bullying among
      public high school students in Turkey. METHOD: This study used a survey to
      examine different aspects of bullying in schools. The participants (N = 692) were
      students chosen from five state high schools in Ankara in the 2000-2001 academic
      year. A self-administered questionnaire of 28 single or multiple-choice questions
      was devised by the authors to examine the students' perceptions of bullying in
      schools. Descriptive statistical analyses were used to interpret the data.
      RESULTS: Of the total of 692 students, everyone reported having been bullied.
      Thirty three point five percent had been bullied verbally, 35.5% had been bullied
      physically, 28.3% had been bullied emotionally, and 15.6% had been bullied
      sexually, at least once during the academic year. Victims were faced with one or
      more types of bullying. There were clear gender differences, with boys
      consistently experiencing more physical bullying including kicking-slapping,
      assault with a knife, rude physical jokes, and more verbal bullying including
      name calling and insulting-swearing (all significant at p < .001). Among the four
      types of bullying, the most common forms of bullying faced by girls and boys were
      the same in order: pushing (58.1% girls/63.5% boys) and name-calling
      (44.1%/61.8%). About one-third of the students stated that they did not get any
      help in coping with bullying. The main reason for bullying was pretending to be
      strong (43.1%). Among the four types of bullying in both genders, students
      generally reported negative views about the consequences on them including low
      psychological well-being, poor social adjustment, and psychological distress.
      CONCLUSIONS: Bullying is a serious problem in schools in Turkey and is a matter
      of recent concern. This is the first research investigating bullying in Turkey.
      At the present there is no policy at the central level to deal with bullying. It
      is expected that the results of this study will raise the awareness of students,
      teachers, school principals, and educational managers and parents to the problem.

PMID- 16460803
TI  - Localisation of heavy metals in the midgut epithelial cells of Xenillus
      tegeocranus (Hermann, 1804) (Acari: Oribatida).
AB  - Sites of intracellular metal deposition in the midgut ventriculus and in the
      proventricular glands of Xenillus tegeocranus (Hermann, 1804) (Acari: Oribatida)
      were studied by TEM. The study aimed to obtain new information on the
      ultrastructural features of heavy metal compartmentalisation and elimination
      mechanisms in oribatid mites. Specimens of X. tegeocranus were collected from an
      abandoned mining and smelting area and from an unpolluted site. A large number of
      electron-dense granules (EDGs) were detected: concentric spherocrystals were
      observed mainly in the epithelium of the midgut ventriculus, while homogeneous
      dark granules were found exclusively in proventricular gland cells. The elemental
      composition of EDGs, studied by X-ray microanalysis, showed that midgut cells of
      X. tegeocranus can store metals (Fe, Mn, Zn, Ni, and Cu) in granules. The
      chemical composition of EDGs seems to be influenced by the presence and
      bioavailability of heavy metals in soil, with different kinds of metals
      accumulating in different types of granules.

PMID- 16460804
TI  - Comparative nitric oxide production by LPS-stimulated monocyte-derived
      macrophages from Ovis canadensis and Ovis aries.
AB  - Bighorn sheep are more susceptible to respiratory infection by Mannheimia
      haemolytica than are domestic sheep. In response to bacterial challenge,
      macrophages produce a number of molecules that play key roles in the inflammatory
      response, including highly reactive nitrogen intermediates such as nitric oxide
      (NO). Supernatants from monocyte-derived macrophages cultured with M. haemolytica
      LPS were assayed for nitric oxide activity via measurement of the NO metabolite,
      nitrite. In response to LPS stimulation, bighorn sheep macrophages secreted
      significantly higher levels of NO compared to levels for non-stimulated
      macrophages. In contrast, levels of NO produced by domestic sheep macrophages in
      response to M. haemolytica LPS did not differ from levels detected in non
      stimulated cell cultures. Nitrite levels detected in supernatants of LPS
      stimulated bighorn macrophage cultures treated with an inducible nitric oxide
      synthase (INOS) inhibitor, N(G)-monomethyl-L-arginine, were similar to that
      observed in non-stimulated cultures indicating a role for the iNOS pathway.

PMID- 16460805
TI  - The presence of multiple and differentially regulated interleukin-12p40 genes in
      bony fishes signifies an expansion of the vertebrate heterodimeric cytokine
      family.
AB  - Interleukin-12 (IL-12) is the founding member of a rapidly growing family of
      heterodimeric cytokines. It consists of two subunits, designated p35 and p40 that
      together constitute a disulphide-linked heterodimeric cytokine. IL-12 is well
      known for its prominent role in both the early innate immune response and the
      skewing of the ensuing acquired immune response towards Th1. Here, we report the
      presence of IL-12p35 and three highly distinct IL-12p40 genes in common carp
      (Cyprinus carpio). The carp is a bony fish species genetically similar to the
      zebrafish, but its substantially larger body size facilitates immunological
      studies. A comparison of IL-12p35 genes of mammalian and non-mammalian species
      reveals the presence of a duplicated exon that is unique to the mammalian
      lineage. The organisation of the three carp IL-12p40 genes is similar to that of
      higher vertebrates. Phylogenetic analyses that include the p40-related subunits
      of other composite cytokines confirm the presence of three genuine IL-12p40 genes
      in carp and indicate that they are evolutionary ancient and possibly not
      restricted to bony fishes. The orthology of the different carp p40 subunits to
      mammalian IL-12p40 is further evident from the conservation of key residues
      involved in the formation of intra- and interchain disulphide bridges and the
      tight interlocking topology between p35 and p40. The expression of each of the
      carp IL-12p40 genes differs profoundly, constitutively as well as in response to
      in vitro stimulation of carp macrophages. Collectively, the presence of multiple
      and substantially different IL-12 genes signifies a considerable expansion of the
      vertebrate heterodimeric cytokine family.

PMID- 16460806
TI  - The transport of manganese across the blood-brain barrier.
AB  - The mammalian central nervous system (CNS) possesses a unique and specialized
      capillary adaptation, referred to as the blood-brain barrier (BBB). The BBB
      maintains an optimal neuronal microenvironment, regulating blood-tissue exchange
      of macromolecules and nutrients. The BBB is characterized by individual
      endothelial cells that are continuously linked by tight junctions, inhibiting the
      diffusion of macromolecules and solutes between adjacent endothelial cells. This
      review will focus on pertinent issues to BBB maintenance, and survey recent
      dogmas on the transport mechanisms for the essential metal, manganese, across
      this barrier. Specifically, putative carriers for manganese into and out of the
      brain will be discussed.

PMID- 16460807
TI  - Pulmonary mycobacteriosis in a patient affected by mycosis fungoides: a
      diagnostic and therapeutic challenge.
AB  - Among patients with cutaneous T-cell lymphoma (CTCL), sepsis and pulmonary
      infections are the first cause of death. We report on a patient with CTCL who,
      after more than 10 years of aggressive antineoplastic treatments, showed
      extensive pulmonary infiltrations on staging CT scan. Repeated CT scans were
      inconclusive for an infectious process, and the patient was still asymptomatic.
      The diagnosis of mycobacteriosis was made on the microbiologic exam of
      bronchoalveolar lavage. Specific treatment was started with contemporary dosage
      reduction of chemotherapy. After six months of antibiotic treatment the pulmonary
      lesions improved, whereas CTCL progressed. Therefore, a new antineoplastic
      regimen was started obtaining control of CTCL, without aggravation of the
      pulmonary lesions. We highlight the diagnostic and therapeutic pitfalls
      encountered when pulmonary mycobacteriosis complicates the course and treatment
      of CTCL.

PMID- 16460809
TI  - Endotoxic fever: new concepts of its regulation suggest new approaches to its
      management.
AB  - Endotoxic fever is regulated by endogenous factors that provide pro- and anti
      pyretic signals at different points along the febrigenic pathway, from the
      periphery to the brain. Current evidence indicates that the febrile response to
      invading Gram-negative bacteria and their products is initiated upon their
      arrival in the liver via the circulation and their uptake by Kupffer cells (Kc).
      These pathogens activate the complement cascade on contact, hence generating
      complement component 5a. It, in turn, very rapidly stimulates Kc to release
      prostaglandin (PG)E2. Pyrogenic cytokines (TNF-alpha, etc.) are produced later
      and are no longer considered to be the immediate triggers of fever. The Kc
      generated PGE2 either (1) may be transported by the bloodstream to the
      ventromedial preoptic-anterior hypothalamus (POA, the locus of the temperature
      regulating center), presumptively diffusing into it and acting on
      thermoregulatory neurons; PGE2 is thus taken to be the final, central fever
      mediator. Or (2) it may activate hepatic vagal afferents projecting to the
      medulla oblongata, thence to the POA via the ventral noradrenergic bundle.
      Norepinephrine consequently secreted stimulates alpha1-adrenoceptors on
      thermoregulatory neurons, rapidly evoking an initial rise in core temperature
      (Tc) not associated with any change in POA PGE2; this neural, PGE2-independent
      signaling pathway is quicker than the blood-borne route. Elevated POA PGE2 and a
      secondary Tc rise occur later, consequent to alpha2 stimulation. Endogenous
      counter-regulatory factors are also elaborated peripherally and centrally at
      different points during the course of the febrile response; they are, therefore,
      anti-pyretic. These multiple interacting pathways are the subject of this review.

PMID- 16460810
TI  - Synaptic release of zinc from brain slices: factors governing release, imaging,
      and accurate calculation of concentration.
AB  - Cerebrocortical neurons that store and release zinc synaptically are widely
      recognized as critical in maintenance of cortical excitability and in certain
      forms of brain injury and disease. Through the last 20 years, this synaptic
      release has been observed directly or indirectly and reported in more than a
      score of publications from over a dozen laboratories in eight countries. However,
      the concentration of zinc released synaptically has not been established with
      final certainty. In the present work we have considered six aspects of the
      methods for studying release that can affect the magnitude of zinc release, the
      imaging of the release, and the calculated concentration of released zinc. We
      present original data on four of the issues and review published data on two
      others. We show that common errors can cause up to a 3000-fold underestimation of
      the concentration of released zinc. The results should help bring consistency to
      the study of synaptic release of zinc.

PMID- 16460811
TI  - Interleukin-18 mRNA expression in the rat pituitary gland.
AB  - The present study investigated the expression of IL-18 mRNA under several
      stimuli, and molecular structures of IL-18 mRNA of the rat pituitary. Real-time
      PCR demonstrated that IL-18 mRNA, highly expressed in anterior pituitary,
      significantly increased following stress and adrenalectomy. In situ hybridization
      combined with immunohistochemistry demonstrated that corticotrope cells expressed
      IL-18 mRNA. RACE and sequence analysis demonstrated that pituitary IL-18 mRNA
      possesses five new exons at the upstream of exon 1 and between exon 1 and exon 2,
      indicating the preferential usage of promoter 1. The present study suggests that
      IL-18 in the corticotrope cells may play some roles in stress responses.

PMID- 16460812
TI  - Characteristics of lacrimo-auriculo-dento-digital (LADD) syndrome: case report of
      a family and literature review.
AB  - We describe a family with lacrimo-auriculo-dento-digital syndrome (LADD). A 13
      year-old boy had cup-shaped ears, deafness, unilateral choanal atresia, bilateral
      nasolacrimal duct obstruction, xerostomia, alacrima due to congenital absence of
      lacrimal glands, agenesis of salivary glands, chronic dacryocystitis,
      keratoconjunctivitis sicca, ptosis, nail dysplasia of the thumb, shortness of
      fifth toe, temporal bone abnormality and epilepsy. His younger sister had
      shortened middle phalanx of fifth digits. His middle sister had hypodontia,
      shortened distal phalanx of fifth digit, agenesis of salivary glands, mild
      hearing loss and exotropia. His older sister had left nasolacrimal duct
      obstruction and aplasia of both parotid glands. The oldest sister had hypodontia
      and divergent excess exotropia. His mother had hypodontia. These findings are
      consistent with LADD syndrome. An autosomal dominant pattern of inheritance with
      variable expressivity has been demonstrated. Renal and uro-genital anomalies have
      been noted variably.

PMID- 16460814
TI  - Acoustic and perceptual appraisal of speech production in pediatric cochlear
      implant users.
AB  - OBJECTIVE: The purpose of the present study was to examine the relationship
      between objectively measurable acoustic changes in speech production and
      subjective speech production accuracy and perceived intelligibility immediately
      following a disruption in auditory feedback normally provided to subjects from a
      cochlear implant. METHODS: Six children with profound sensorineural hearing loss
      participated in the study. Their task was to produce speech samples in two
      conditions: (1) with auditory feedback from their cochlear implants, and (2)
      without auditory feedback from their cochlear implants. Samples were subjected to
      both objective and subjective analyses. Objectively, measures were made of
      duration, fundamental frequency, and the first and second formants of the vowels.
      Subjectively, two groups of listeners, one familiar with the speech of children
      with hearing loss and the other unfamiliar, transcribed the productions and
      provided ratings of intelligibility. RESULTS: All the children in this study
      exhibited significant differences from the cochlear implant-on to the cochlear
      implant-off condition, although these changes were not always in the predicted
      direction, nor were they always perceptually salient. CONCLUSIONS: Consistent
      with previous studies, children in this investigation demonstrated variable
      acoustic voice and speech changes following deactivation of their cochlear
      implant device. Few of these acoustic changes affected speech intelligibility.
      The results of this study overall suggest that during the initial years following
      implantation children who are deaf rely to some extent on the auditory feedback
      provided by a cochlear implant to control and modify F0, duration, and vowel
      formant production.

PMID- 16460813
TI  - Endoscopically guided placement of prefabricated cochlear implant electrodes in a
      common cavity malformation.
AB  - OBJECTIVE: To devise a safe and effective method of optimal customized electrode
      placement in the common cavity of children with cochleovestibular malformations.
      METHODS: Specialized electrodes were manufactured on the basis of three
      dimensional data obtained from the high resolution computed tomography (HRCT)
      scans of the temporal bones of these two children. Electrode positioning was
      achieved with direct endoscopic view of the cavity utilizing a three-hole common
      cavity technique. RESULTS: Optimal electrode positioning in apposition to the
      medial neuroepithelium in the common cavity was verified visually
      intraoperatively. Postoperatively, minimal stable electrical current levels were
      found to be required. CONCLUSIONS: Custom-designed electrodes have the potential
      to offer improved results in children with common cavity malformations.
      Intraoperative direct positioning may further improve these results.

PMID- 16460815
TI  - Lymphatic malformations of the head and neck: introduction of a disease score for
      children, Cologne Disease Score (CDS).
AB  - OBJECTIVE: A clinical staging system for children with lymphatic malformations
      that would allow for a standardized comparison of disease and treatment outcomes.
      METHODS: We developed an examination sheet for the determination of a disease
      score ranging from 0 (worst) points to 10 (best) points, Cologne Disease Score
      (CDS). Disfigurement, dysphagia, dysphonia, dyspnea and an observer statement
      towards progression were contributing to CDS. Each parameter yielded two, one or
      zero points. Two points were given when no limitation was seen in the patient
      concerning the respective item. One point was given at mild limitation and zero
      points were given when considerable limitation in the respective item could be
      observed. We evaluated 26 patients with lymphatic malformations of the head and
      neck retrospectively by completing one examination sheet for each patient-visit.
      RESULTS: Four patients had an initial CDS value of three or less points (severe
      disease-group). After therapy the mean value of their score increased only
      slightly to 3.9+/-2.6 points. Six patients had an initial CDS value of four, five
      or six points (advanced disease-group). After treatment their mean score value
      increased dramatically to 9.0+/-1.5 points (P<0.001). Sixteen patients initially
      had seven points or higher (moderate disease-group), they had 9.8+/-0.4 points
      after treatment. CONCLUSIONS: The evaluation of the CDS was easy and expeditious.
      The score itself was a good predictor in view of the outcome. This new disease
      score for paediatric patients might be appropriate to evaluate therapeutic trials
      in paediatric patients.

PMID- 16460808
TI  - The structural basis of arrestin-mediated regulation of G-protein-coupled
      receptors.
AB  - The 4 mammalian arrestins serve as almost universal regulators of the largest
      known family of signaling proteins, G-protein-coupled receptors (GPCRs).
      Arrestins terminate receptor interactions with G proteins, redirect the signaling
      to a variety of alternative pathways, and orchestrate receptor internalization
      and subsequent intracellular trafficking. The elucidation of the structural basis
      and fine molecular mechanisms of the arrestin-receptor interaction paved the way
      to the targeted manipulation of this interaction from both sides to produce very
      stable or extremely transient complexes that helped to understand the regulation
      of many biologically important processes initiated by active GPCRs. The
      elucidation of the structural basis of arrestin interactions with numerous non
      receptor-binding partners is long overdue. It will allow the construction of
      fully functional arrestins in which the ability to interact with individual
      partners is specifically disrupted or enhanced by targeted mutagenesis. These
      "custom-designed" arrestin mutants will be valuable tools in defining the role of
      various interactions in the intricate interplay of multiple signaling pathways in
      the living cell. The identification of arrestin-binding sites for various
      signaling molecules will also set the stage for designing molecular tools for
      therapeutic intervention that may prove useful in numerous disorders associated
      with congenital or acquired disregulation of GPCR signaling.

PMID- 16460816
TI  - Growth failure and sleep disordered breathing: a review of the literature.
AB  - OBJECTIVE: While otolaryngologists consider growth failure an absolute indication
      for tonsillectomy and adenoidectomy (T&A), they may not be accustomed to
      screening for poor growth, and thus unlikely to consider it when recommending a
      T&A. This paper will (a) familiarize otolaryngologists with the definition,
      prevalence, and etiology of growth failure and (b) review the published findings
      that examine the inter-relationship among sleep disordered breathing, growth
      failure, and adentonsillar hypertrophy in children. METHODS: This paper is
      divided into three sections. The first section presents a brief overview of
      growth failure for the otolaryngologist. The second section reviews the evidence
      base linking sleep disordered breathing, growth failure, and adenotonsillar
      hypertrophy in children. The anthropometric outcomes of children presenting for
      T&A, or having sleep symptoms assessed, are presented. The third section presents
      pilot data (n=28) on the prevalence of growth failure and sleep disordered
      breathing among children presenting for T&A at our institution. RESULTS: Among
      children presenting for T&A or having sleep symptoms assessed, growth failure was
      at least twice the expected rate in six of eight published studies. Across these
      six studies, this rate ranged from a low of 6% of children <3rd percentile for
      weight and 6% <3rd percentile for height in one study, to a high of 52% who were
      <3rd percentile in weight in a second study, and 44% who were <or= 5th percentile
      for height in a third. Among children presenting for T&A at our own institution,
      14% were <or=5th percentile in height, and 11% were <or=5th percentile in weight.
      Among children under 6 years of age, 21% were either <or= 5th percentile in
      weight and/or height. CONCLUSIONS: Published studies, as well as our own pilot
      data support the hypothesis that SDB, secondary to adenotonsillar hypertrophy
      increases the risk of growth failure in children. Adenotonsillar hypertrophy and
      sleep disordered breathing may be unrecognized risk factors in the etiology of
      growth failure. Otolaryngologists can play an important role in identifying
      growth failure, and referring children to the appropriate specialists.

PMID- 16460817
TI  - Amino acid insertions at position 35 of HIV-1 protease interfere with virus
      replication without modifying antiviral drug susceptibility.
AB  - Among 1330 patients undergoing highly active antiretroviral therapy (HAART), 3
      showed 1 or 2 amino acid (aa) insertions at position 35 of the HIV-1 protease
      gene. Protease genes containing aa insertions, either in the presence
      (ins35G+res.muts, ins35TN+res.muts) or absence (ins35G, ins35TN) of other
      resistance mutations, were introduced into the wild-type HIV-1 strain NL4-3. The
      introduction of ins35G and ins35TN in the wild-type protease confirmed that these
      mutations were per se not responsible of decreased drug susceptibility. The
      replication rate of mutant recombinant viruses was determined by HIV RNA
      quantification in supernatants of cell cultures in comparison with a recombinant
      HIV-1 strain with wild-type protease. Recombinant ins35G and ins35TN HIV-1
      strains did not display increased resistance to currently used protease
      inhibitors (PIs). Comparison of ins35TN+res.muts and ins35G+res.muts with respect
      to the corresponding recombinant rescue mutants showed that ins35TN decreased the
      replication rate of the PI-resistant strain, while ins35G had a protective
      effect.

PMID- 16460818
TI  - Dynamic relocation of poly(ADP-ribose) glycohydrolase isoforms during radiation
      induced DNA damage.
AB  - Poly(ADP-ribosyl)ation is a very early cellular response to DNA damage. Poly(ADP
      ribose) (PAR) accumulation is transient since PAR is rapidly hydrolyzed by
      poly(ADP-ribose) glycohydrolase (PARG). PARG may play a prominent role in DNA
      damage response and repair by removing PAR from modified proteins including PARP
      1. Using living cells, we provide evidence that in response to DNA damage induced
      by gamma-irradiation the cytoplasmic 103 kDa PARG isoform translocates into the
      nucleus. We further observed that the nuclear GFP-hPARG110 enzyme relocalizes to
      the cytoplasm in response to DNA damage. Using different GFP-PARG fusion proteins
      specific for the nuclear and cytoplasmic forms, we demonstrate their dynamic
      distribution between cytoplasm and nucleoplasm and a high mobility of major PARG
      isoforms by fluorescence recovery after photobleaching (FRAP). The dynamic
      relocation of all PARG isoforms presented in this report reveals a novel
      biological mechanism by which PARG could be involved in DNA damage response.

PMID- 16460819
TI  - Antibiotic efficacy and microbial virulence during space flight.
AB  - Human space flight is a complex undertaking that entails numerous technological
      and biomedical challenges. Engineers and scientists endeavor, to the extent
      possible, to identify and mitigate the ensuing risks. The potential for an
      outbreak of an infectious disease in a spacecraft presents one such concern,
      which is compounded by several components unique to an extraterrestrial
      environment. Various factors associated with the space flight environment have
      been shown to potentially compromise the immune system of astronauts, increase
      microbial proliferation and microflora exchange, alter virulence and decrease
      antibiotic effectiveness. An acceptable resolution of the above concerns must be
      achieved to ensure safe and efficient space habitation. To help bring this about,
      scientists are employing advances in biotechnology to better characterize the
      relevant variables and establish appropriate solutions. Because many of these
      clinical concerns are also relevant in terrestrial society, this research will
      have reciprocal benefits back on Earth.

PMID- 16460820
TI  - Unintended effects in genetically modified crops: revealed by metabolomics?
AB  - In Europe the commercialization of food derived from genetically modified plants
      has been slow because of the complex regulatory process and the concerns of
      consumers. Risk assessment is focused on potential adverse effects on humans and
      the environment, which could result from unintended effects of genetic
      modifications: unintended effects are connected to changes in metabolite levels
      in the plants. One of the major challenges is how to analyze the overall
      metabolite composition of GM plants in comparison to conventional cultivars, and
      one possible solution is offered by metabolomics. The ultimate aim of
      metabolomics is the identification and quantification of all small molecules in
      an organism; however, a single method enabling complete metabolome analysis does
      not exist. Given a comprehensive extraction method, a hierarchical strategy-
      starting with global fingerprinting and followed by complementary profiling
      attempts--is the most logical and economic approach to detect unintended effects
      in GM crops.

PMID- 16460821
TI  - Evaluating genetic containment strategies for transgenic plants.
AB  - One of the primary concerns about genetically engineered crop plants is that they
      will hybridize with wild relatives, permitting the transgene to escape into the
      environment. The likelihood that a transgene will spread in the environment
      depends on its potential fitness impact. The fitness conferred by various
      transgenes to crop and/or wild-type hybrids has been evaluated in several
      species. Different strategies have been developed for reducing the probability
      and impact of gene flow, including physical separation from wild relatives and
      genetic engineering. Mathematical models and empirical experimental evidence
      suggest that genetic approaches have the potential to effectively prevent
      transgenes from incorporating into wild relatives and becoming established in
      wild populations that are not reproductively isolated from genetically engineered
      crops.

PMID- 16460822
TI  - Employing epigenetics to augment the expression of therapeutic proteins in
      mammalian cells.
AB  - Recombinant proteins form an increasingly large part of the portfolio of
      biopharmaceutical companies. Production of these often complex transgenic
      proteins is achieved predominantly in mammalian cell lines but the process is
      hampered by low yields and unstable expression. Some of these problems are caused
      by gene silencing at the level of chromatin - so-called epigenetic gene
      silencing. Here, we describe approaches, which have emerged during the past few
      years, designed to interfere with epigenetic gene silencing with the aim of
      enhancing and stabilizing transgene expression. These include targeting histones,
      the inclusion of specific DNA elements and targeting sites of high gene
      expression. We conclude that employing epigenetic gene regulation tools, in
      combination with further process optimization, might represent the next step
      forward in the production of therapeutic proteins.

PMID- 16460823
TI  - Cardiovascular and respiratory responses during musical mood induction.
AB  - Music is used to induce moods in experimental settings as well as for therapeutic
      purposes. Prior studies suggest that subjects listening to certain types of music
      experience strong moods and show physiological responses associated with the
      induced emotions. We hypothesized that cardiovascular and respiratory patterns
      could discriminate moods induced via music. 18 healthy subjects listened to 12
      music clips, four each to induce happiness, sadness, and fear, while
      cardiovascular and respiratory responses were recorded using an electrocardiogram
      and chest strain-gauge belt. After each clip subjects completed a questionnaire.
      Subjects consistently reported experiencing the targeted mood, suggesting
      successful mood induction. Cardiovascular activity was measured by calculating
      time domain measures and heart rate changes during each clip. Respiratory
      activity was measured by total, inspiration, and expiration lengths as well as
      changes in mean respiration rate during each clip. Evaluation of individuals'
      patterns and mixed-model analyses were performed. Contrary to expectations, the
      time domain measures of subjects' cardiovascular responses did not vary
      significantly between the induced moods, although a heart rate deceleration was
      found during the sadness inductions and acceleration during the fear inductions.
      The time domain respiratory measures varied with clip type: the mean breath
      length was longest for the sad induction, intermediate during fear, and shortest
      during the happiness induction. However, analysis using normalized least mean
      squares adaptive filters to measure time correlation indicated that much of this
      difference may be attributable to entrainment of respiration to characteristics
      of the music which varied between the stimuli. Our findings point to the
      difficulty in detecting psychophysiological correlates of mood induction, and
      further suggest that part of this difficulty may arise from failure to
      differentiate it from tempo-related contributions when music is used as the
      inducer.

PMID- 16460824
TI  - Speed-accuracy trade-offs in myocontrol.
AB  - Myoelectric (EMG) signals are used in assistive technology for prostheses,
      computer and domestic control. However, little is known about the capacity of
      controlling these signals. Specifically, it is unclear whether myocontrol, i.e.,
      the control of myoelectric signals, obeys the same laws as motor control.
      Neurologically intact adult participants performed pointing tasks with EMG
      signals captured from the forehead or the hand in two modalities (sustained:
      stabilize the signal amplitude in the target; impulsion: produce an impulse and
      return to resting level). In the sustained modality, the time to reach the target
      (reach time) increased logarithmically with target amplitude, which is compatible
      with the predictions of Fitts' law. The rate of failure was not significantly
      affected by target amplitude. In the impulsion modality, the reach time and the
      rate of failure followed a bow-shaped pattern as a function of target amplitude.
      Stabilization time in the sustained modality followed a convex (bow-shaped)
      pattern for the forehead and a concave pattern for the hand. This was the only
      significant effect of electrode placement in this study. These findings suggest
      that myocontrol obeys laws that are distinct from those determining motor
      control, and that the muscular and intra-muscular synergies that produce EMG
      signals are specific of each pointing modality and target amplitude.

PMID- 16460825
TI  - Recombinant human erythropoietin produced in milk of transgenic pigs.
AB  - We have developed a line of transgenic swine harboring recombinant human
      erythropoietin through microinjection into fertilized one cell pig zygotes. Milk
      from generations F1 and F2 transgenic females was analyzed, and hEPO was detected
      in milk from all lactating females at concentrations of approximately 877.9+/
      92.8 IU/1 ml. The amino acid sequence of rhEPO protein in the transgenic pig milk
      matched that of commercial rhEPO produced from cultured animal cells. In
      addition, an F-36 cell line, which proliferates in the presence of hEPO or
      commercial EPO, was induced to synthesize erythroid by extracts from tg sow milk.
      This study provides evidence that production of purified rhEPO from transgenic
      pig milk is a potentially valuable technology, and can be used as a cost
      effective alternative in clinical applications as well as providing other
      clinical advantages.

PMID- 16460826
TI  - Unfolding the evolutionary story of polydnaviruses.
AB  - Polydnaviruses (PDVs) are fascinating viruses. Described in thousands of
      parasitoid wasp species they are unique viruses having both a segmented DNA
      genome in viral particles and an integrated form that persists as a provirus in
      the wasp genome. Parasitoid wasps inject their eggs in another insect host
      typically a lepidopteran. In these host-parasitoid interactions, the virus
      particles are co-injected along with the eggs and are essential to ensure wasp
      parasitism success. PDVs do not replicate in the lepidopteran host, but
      expression of viral gene products confers protection from the host immune defence
      response. Two genera of PDVs phylogenetically unrelated exist, the bracoviruses
      (BVs) and the ichnoviruses (IVs), associated with braconid and ichneumonid wasps,
      respectively. New data on the genomes of two bracoviruses (Microplitis demolitor
      BV and Cotesia congregata BV) and an ichnovirus associated with Campoletis
      sonorensis (CsIV) offers us new elements to discuss the central questions
      concerning the origin of these viral entities and how they have evolved. The
      results of sequencing approaches indicate that the tens of millions of years of
      mutualistic associations between PDVs and wasps have had a strong impact on PDV
      genomes that now ressemble eukaryotic regions both in organization and gene
      content.

PMID- 16460827
TI  - Sumoylation of Rta of Epstein-Barr virus is preferentially enhanced by PIASxbeta.
AB  - Epstein-Barr virus (EBV) expresses an immediate-early protein, Rta, to activate
      the viral lytic cycle. This study identifies PIASxalpha and PIASxbeta as binding
      partners of Rta in a yeast two-hybrid screen and demonstrates the binding of Rta
      to PIASxalpha and PIASxbeta in vitro by GST pull-down analysis.
      Coimmunoprecipitation experiments and indirect immunofluorescence analysis show
      that Rta interacts and colocalizes with PIASxalpha and PIASxbeta in the nucleus.
      These interactions seem to enhance Rta sumoylation as transfecting plasmids
      expressing PIASxalpha, PIASxbeta, Ubc9, or SUMO-1 increase the capacity of Rta to
      transactivate a promoter that contains an Rta-response element and the promoters
      of p21 and BNLF1 in transient transfection assay. This study also finds that Rta
      sumoylation is preferentially enhanced by PIASxbeta, which could be attributed to
      the fact that PIASxbeta, compared to PIASxalpha, has a strong affinity to Rta,
      suggesting that affinity of a SUMO E3 ligase to its target protein influences the
      function of protein sumoylation.

PMID- 16460828
TI  - Electron spin resonance microscopy applied to the study of controlled drug
      release.
AB  - We describe our recent developments towards 3D micron-scale imaging capability,
      based on electron spin resonance (ESR), and its application to the study of
      controlled release. The method, termed ESR microscopy (ESRM), is an extension of
      the conventional "millimeter-scale" ESR imaging technique. It employs
      paramagnetic molecules (such as stable radicals or spin-labeled drugs) and may
      enable one to obtain accurate 3D spatially resolved information about the drug
      concentration, its self-diffusion tensor, rotational correlation time and the pH
      in the release matrix. Theoretical calculations, along with initial experimental
      results, suggest that a 3D resolution of approximately 1 microm is feasible with
      this method. Here we were able to image successfully a high spin concentration
      sample with a resolution of approximately 3 x 3 x 8 microm and subsequently study
      a single approximately 120 microm biodegradable microsphere, internalized with a
      dilute solution of trityl radical, with a resolution of approximately 12.7 x 13.2
      x 26 microm. Analysis of the microsphere ESR imaging data revealed a likely
      increase in the viscosity inside the sphere and/or binding of the radical
      molecule to the sphere matrix. Future directions for progress are also discussed.

PMID- 16460829
TI  - Intestinal uptake and biodistribution of novel polymeric micelles after oral
      administration.
AB  - To determine the fate of polymeric micelles after oral administration, we
      investigated the possible transport of polymeric micelles across Caco-2
      monolayers and their biodistribution in rats after per os administration of [14C]
      labelled mmePEG750P(CL-co-TMC) micelles containing risperidone (BCS Class II
      drug). mmePEG750P(CL-co-TMC) was able to cross Caco-2 monolayer via a saturable
      transport mechanism. The oral bioavailability of the polymer was 40%. Polymeric
      micelles based on mmePEG750P(CL-co-TMC) showed very low clearance by the
      reticuloendothelial system (RES) and a renal excretion. A sustained release of
      risperidone was observed.

PMID- 16460830
TI  - Loading and mobility of spin-labeled insulin in physiologically responsive
      complexation hydrogels intended for oral administration.
AB  - Poly(methacrylic acid-g-ethylene glycol) copolymers are pH-responsive
      complexation hydrogels that have shown promise in in vitro and in vivo results as
      oral insulin delivery carriers. With the aim of gaining more detailed insight
      into their performance to further improve the carriers, we spin-labeled insulin
      and used electron spin resonance (ESR) spectroscopy to follow the loading of the
      spin-labeled insulin into the copolymer microparticles. A flow through system was
      developed to monitor continuously and non-invasively the dynamics of the spin
      labeled insulin and its surrounding microviscosity during release. Using these
      methods, the loading efficiency of insulin was determined and was found to match
      previous HPLC measurements. Additionally, the protein-friendly nature of the
      hydrogels was demonstrated. The monitoring of the dynamics during flow through
      provided a rationalization for the unwanted initial burst release in an acidic
      environment. These studies will aid in the optimization of the system, and will
      be a basis for subsequent in vivo ESR investigations.

PMID- 16460831
TI  - Hepcidin generated by hepatoma cells inhibits iron export from co-cultured THP1
      monocytes.
AB  - BACKGROUND/AIMS: The antimicrobial peptide hepcidin is generated in the liver and
      released into the circulation in response to iron, oxygen and inflammatory
      signals. Hepcidin serves as a hormonal regulator of duodenal iron absorption and
      iron trafficking in the reticuloendothelial system. The aim of this study is to
      explore the effects of this regulatory peptide in macrophage iron metabolism.
      METHODS: Hepcidin-mediated iron efflux and parameters of cellular iron
      homeostasis were studied in THP1 monocytic cells co-cultured with hepcidin
      producing hepatic cells. RESULTS: Stimulation of hepcidin expression in Huh7
      cells with interleukin-6 promoted a significant approximately 30% decrease in
      59Fe efflux from THP1 cells, previously loaded with 59Fe-transferrin. Similar
      results were obtained with HepG2 cells transfected with a hepcidin cDNA.
      Importantly, hepcidin expression from Huh7 cells elicited a decrease in the
      levels of the iron-sensitive post-transcriptional regulator IRP2 in THP1 cells,
      accompanied by de novo synthesis of the iron storage protein ferritin.
      CONCLUSIONS: Physiologically generated hepcidin inhibits iron efflux and promotes
      iron accumulation in monocytic cells, mimicking a pathophysiological response
      commonly observed in the anemia of inflammation. Our results highlight the
      crucial role of hepcidin in the control of macrophage iron homeostasis.

PMID- 16460832
TI  - Recoding in bacteriophages and bacterial IS elements.
AB  - Dynamic shifts between open reading frames and the redefinition of codon meaning
      at specific sites, programmed by signals in mRNA, permits versatility of gene
      expression. Such alterations are characteristic of organisms in all domains of
      life and serve a variety of functional purposes. In this article, we concentrate
      on programmed ribosomal frameshifting, stop codon read-through and
      transcriptional slippage in the decoding of phage genes and bacterial mobile
      elements. Together with their eukaryotic counterparts, the genes encoding these
      elements are the richest known source of nonstandard decoding. Recent analyses
      revealed several novel sequences encoding programmed alterations in gene decoding
      and provide a glimpse of the emerging picture.

PMID- 16460833
TI  - Protein kinase A targeting and activation as seen by small-angle solution
      scattering.
AB  - We have studied the solution structures of the multi-functional protein kinase A
      using small-angle X-ray and neutron scattering and have found a remarkable
      structural diversity in the different isoforms of this multi-subunit enzyme, in
      spite of its having high sequence homology and a common domain organization
      within its sequences. The available high-resolution crystal and NMR structural
      data for the protein kinase A components have aided in the interpretation of the
      solution scattering data and enabled us to develop models that bring insights
      into protein kinase A activation and targeting mechanisms, such as the opening
      and closing of the catalytic cleft to facilitate substrate binding or inhibition,
      respectively, and the role of sequence segments that join functional domains in
      the R subunit in providing a structurally flexible scaffold for interactions with
      the C subunit and A kinase-anchoring proteins (AKAPs).

PMID- 16460834
TI  - The mAKAP signaling complex: integration of cAMP, calcium, and MAP kinase
      signaling pathways.
AB  - Following its production by adenylyl cyclases, the second messenger cAMP is in
      involved in pleiotrophic signal transduction. The effectors of cAMP include the
      cAMP-dependent protein kinase (PKA), the guanine nucleotide exchange factor Epac
      (exchange protein activated by cAMP), and cAMP-dependent ion channels. In turn,
      cAMP signaling is attenuated by phosphodiesterase-catalyzed degradation. The
      association of cAMP effectors and the enzymes that regulate cAMP concentration
      into signaling complexes helps to explain the differential signaling initiated by
      members of the G(s)-protein coupled receptor family. The signal transduction
      complex formed by the scaffold protein mAKAP (muscle A kinase-anchoring protein)
      at the nuclear envelope of both striated myocytes and neurons contains three cAMP
      binding proteins, PKA, Epac1, and the phosphodiesterase PDE4D3. In addition, the
      mAKAP complex also contains components of the ERK5 MAP kinase signaling pathway,
      the calcium release channel ryanodine receptor and the phosphatases PP2A as well
      as calcineurin. Analysis of the mAKAP complex illustrates how a macromolecular
      complex can serve as a node in the intracellular signaling network of cardiac
      myocytes to integrate multiple cAMP signals with those of calcium and MAP kinases
      to regulate the hypertrophic actions of several hormones.

PMID- 16460835
TI  - Tissue-specific expression of Clec2g in mice.
AB  - Estrogens regulate the proliferation and differentiation of mouse vaginal
      epithelial cells. We examined the temporal and spatial expression of DDV10, a
      novel C-type lectin during stratification and cornification of the vaginal
      epithelium. DDV10 was expressed in vagina but not uterus in ovariectomized mice
      treated with 17beta-estradiol (E2). In mouse stomach, the expression of DDV10 was
      detected in pars proventricularis but not in pars glandularis. Furthermore, the
      DDV10 gene was found to possess two transcripts, a long form (DDV10) and a short
      form (OCILrP1, osteoclast inhibitory lectin-related protein 1). DDV10 mRNA but
      not OCILrP1 mRNA was expressed in the stratified and cornified epithelial
      tissues. DDV10 mRNA was first detected between 12 and 18 h after E2 treatment in
      the vaginal epithelium, and was detected in the vagina of the neonatally
      diethylstilbestrol (DES)-treated mouse. Recently, a unified name was registered
      in GenBank (C-type lectin domain family 2, member g; Clec2 g). Taken together,
      these data suggest that DDV10 is the long form of Clec2 g (Clec2g-L), and
      DDV10/Clec2g-L may play a role in the stratification and/or cornification of
      epithelial cells during differentiation.

PMID- 16460836
TI  - Contextual utilization of enzymes in discrete AKAP79/150 signalling complexes.
AB  - Cellular function involves the concerted action of signal transduction enzymes.
      Restriction of enzyme location contributes to the fidelity of each cellular
      response. A kinase-anchoring proteins (AKAPs) target the cAMP-dependent protein
      kinase and other signalling enzymes to defined subcellular locations. We have
      developed a new strategy that combines RNA interference of the endogenous protein
      and replacement with AKAP79/150 forms unable to anchor selected binding partners.
      Using this approach we show that AKAP79/150 coordinates different enzyme
      combinations to modulate the activity of two distinct neuronal ion channels: AMPA
      type glutamate receptors and M-type potassium channels. Utilization of distinct
      enzyme combinations in this manner provides a means to expand the repertoire of
      cellular events that the same AKAP modulates.

PMID- 16460837
TI  - AKAP-Lbc: a molecular scaffold for the integration of cyclic AMP and Rho
      transduction pathways.
AB  - A Kinase-anchoring proteins (AKAPs) are a family of functionally related proteins
      involved in the targeting of the PKA holoenzyme towards specific physiological
      substrates. We have recently identified a novel anchoring protein expressed in
      cardiomyocytes, called AKAP-Lbc, that functions as a PKA-targeting protein as
      well as a guanine nucleotide exchange factor (GEF) that activates the GTPase
      RhoA. Here, we discuss the most recent findings elucidating the molecular
      mechanisms and the transduction pathways involved in the regulation of the AKAP
      Lbc signaling complex inside cells. We could show that AKAP-Lbc is regulated in a
      bi-directional manner by signals that activate or deactivate its Rho-GEF
      activity. Activation of AKAP-Lbc occurs in response to agonists that stimulate G
      proteins coupled receptors linked to the heterotrimeric G protein G12, whereas
      inactivation occurs through mechanisms that require phosphorylation of AKAP-Lbc
      by anchored PKA and subsequent recruitment of the regulatory protein 14-3-3.
      Interestingly, we could demonstrate that AKAP-Lbc can form homo-oligomers inside
      cells and that 14-3-3 can inhibit the Rho-GEF activity of AKAP-Lbc only when the
      anchoring protein adopts an oligomeric conformation. These findings reveal the
      molecular architecture of the AKAP-Lbc transduction complex and provide a
      mechanistic explanation of how upstream signaling pathways can be integrated
      within the AKAP-Lbc transduction complex to precisely modulate the activation of
      Rho.

PMID- 16460838
TI  - Regulation of podosomes by integrin alphavbeta3 and Rho GTPase-facilitated
      phosphoinositide signaling.
AB  - In osteoclasts, polyphosphoinositides such as phosphatidylinositol 4,5
      bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5 trisphosphate
      (PI(3,4,5)P3) are produced in response to integrin alphavbeta3 signaling and they
      have a critical role in actin cytoskeleton remodeling. The levels of PI(4,5)P2
      and PI(3,4,5)P3 are regulated by Rho GTPase through the activation of
      phosphatidylinositol 4-phosphate 5-kinase (PI4P-5 kinase) and phospatidylinositol
      3-kinase (PI3 kinase), respectively. Interaction of PI(4,5)P2 with gelsolin and
      Wiscott-Aldrich syndrome protein (WASP) is critical for podosome
      assembly/disassembly and actin ring formation in osteoclasts. Interaction of
      PI(3,4,5)P3 with gelsolin functions in orchestrating the podosome signaling
      complex consisting of several key signaling molecules. Gelsolin deficiency has
      been shown to block podosome assembly and motility in mouse osteoclasts. However,
      these osteoclasts are able to form a WASP-containing actin ring and retain their
      resorptive function. The TAT-mediated delivery of gelsolin phosphoinositide
      binding domains into osteoclasts resulted in production of podosome clusters and
      disruption of actin ring formation. Hence, these osteoclasts were hypomotile and
      less resorptive. Our observations suggest that both PI(4,5)P2 and PI(3,4,5)P3 are
      involved in regulating osteoclast functions through modulation of severing,
      capping, and nucleating functions of actin-binding proteins.

PMID- 16460839
TI  - Expression of laminin 5 by parental and c-Ha-ras-transformed HaCaT keratinocytes
      in organotypic cultures.
AB  - Tumor cells traverse the basement membrane zone and gain access to the underlying
      mesenchyme to eventually form metastases. Laminin 5 is a major component of the
      basement membrane and connects keratinocytes at the level of hemidesmosomes to
      the mesenchyme. Underneath invading tumor cells anti-laminin 5 staining is
      diminished, and laminin 5 degradation products can stimulate cell migration and
      epidermal growth factor (EGF) receptor signaling. To investigate laminin 5
      expression in parental HaCaT and tumorigenic c-Ha-ras-transformed HaCaT II-4rt
      keratinocytes, the cells were cultivated under monolayer and organotypic culture
      conditions. In monolayer cultures, HaCaT and c-Ha-ras-transformed HaCaT II-4rt
      keratinocytes secreted comparable amounts of laminin 5. After 7 days of
      organotypic cultures, collagen IV, beta4-integrin, nidogen and laminin 5 were
      detected along the epithelial-mesenchymal interface of parental HaCaT
      keratinocytes, while staining for these proteins was patchy or absent in the
      organotypic cultures with c-Ha-ras-transformed HaCaT II-4rt cells. Immunoblotting
      analysis confirmed absence of laminin 5 deposition in organotypic cultures of c
      Ha-ras-transformed HaCaT II-4rt while the protein was detected in organotypic
      cultures of HaCaT keratinocytes. Surprisingly, however, the alpha3 and gamma2
      laminin chain transcripts were strongly induced in c-Ha-ras-transformed HaCaT II
      4rt cells by organotypic culture conditions, indicating that invasive epidermal
      tumor cells retain high mRNA levels for laminin 5 chains and suggesting an
      autocrine/paracrine induction of the laminin chain mRNAs. Moreover, as laminin 5
      was absent in organotypic cultures of c-Ha-ras-transformed HaCaT II-4rt cells, it
      suggests immediate degradation of the protein. Degradation products may further
      contribute to the malignant phenotype by enhancing cellular migration and EGF
      receptor activation.

PMID- 16460840
TI  - Evaluation of human immunodeficiency virus type 1 subtype C gag, pol, and gagpol
      DNA and alphavirus replicon vaccines.
AB  - The worldwide HIV-1 vaccine research endeavor is focused increasingly on subtype
      C, which is now the predominant strain of the present HIV/AIDS epidemic.
      Expression cassettes of HIV-1 subtype C gag, pol and versions of gagpol fusion
      cassettes were constructed and evaluated for their relative abilities to induce
      cellular immune responses in mice. Animals were vaccinated with DNA or alphavirus
      replicon particle-based vaccines and cellular immune responses were measured by
      flow cytometry. Five new major histocompatibility complex (MHC) class I
      restricted T cell epitopes in subtype C Gag and Pol were identified. Although two
      CD8(+) T cell epitopes within Gag were immunodominant in BALB/c and CB6F1 mice,
      the overall breadth of the T cell responses in mice immunized with plasmids or
      recombinant alphavirus replicon particles encoding gagpol fusion genes was
      improved over single antigen genes (i.e. gag or pol alone). The patterns of
      epitope dominance were consistent among mice although there were variations
      observed between different animals in the relative contributions of the various
      epitopes to the total response. These data are consistent with observations in
      non-human primates (Otten GR, Schaefer M, Doe B, Liu H, Magede JZ, Donnelly J, et
      al. Potent immunogenicity of an HIV-1 gag-pol fusion DNA vaccine delivered by in
      vivo electroporation. Vaccine 2005, in press) and support a subtype C in-frame
      gagpol fusion gene vaccine.

PMID- 16460841
TI  - Immunization with fibrillar Abeta(1-42) in young and aged canines: Antibody
      generation and characteristics, and effects on CSF and brain Abeta.
AB  - We describe a study testing fibrillar beta-amyloid(1-42) (Abeta42) vaccination in
      dogs. Three young beagles (4.6 years) were immunized twice with Abeta42 and a Th1
      adjuvant (TiterMax Gold). Animals generated primarily IgG2 and IgM antibody
      responses, which were specific for the Abeta(11-30) region of Abeta(1-42). Next,
      3 aged beagles (8.9-13.8 years) were immunized 4 times with Abeta(42) and a Th2
      adjuvant (Alum). We observed an acute increase in IgG2, a slower increase in IgG1
      and Abeta antibodies of broader specificity (Abeta(1-15>) Abeta(11-30>) Abeta(6
      20)). A nonsignificant increase in CSF Abeta(1-40) and decrease in Abeta(1-40/1
      42) in cortex was detected. Canines may be a useful system for testing an Abeta
      vaccine.

PMID- 16460842
TI  - Risk of perinatal transmission of rubella and parvovirus B19 in Jordanian
      pregnant women.
AB  - The seroprevalence and the risk of perinatal transmission of rubella virus (RV)
      and human parvovirus B19 were assessed in 439 Jordanian pregnant women.
      Seroprevalence data indicate that 43.7%, 48.7% and 19% of women are susceptible
      to RV, parvovirus B19 infections and both, respectively. A total of 12.2% and
      20.2% of RV susceptible women are at the first and second trimester of gestation,
      respectively. They are at risk of bearing infants with congenital rubella
      syndrome (CRS). However, 15% and 23% of parvovirus B19 susceptible women are at
      the first and second trimester of gestation, respectively. They are at risk of
      fetal loss or hydrops fetalis. Prenatal screening for these viruses, postpartum
      MMR vaccination and parvovirus B19 passive immunization are recommended.

PMID- 16460843
TI  - Natural infection with Japanese encephalitis virus among inhabitants of Japan: a
      nationwide survey of antibodies against nonstructural 1 protein.
AB  - In Japan, only a few cases of Japanese encephalitis presently occur annually,
      raising arguments about the necessity of vaccination. Here, using a novel
      immunoassay, we obtained natural infection rates for 2001 of 0.2-3.4% in eight
      selected prefectures across Japan. Our results provide direct evidence of the
      risk of reemergence.

PMID- 16460845
TI  - Use of available outer membrane vesicle vaccines to control serogroup B
      meningococcal outbreaks.

PMID- 16460844
TI  - Quantifying influenza vaccine efficacy and antigenic distance.
AB  - We introduce a new measure of antigenic distance between influenza A vaccine and
      circulating strains. The measure correlates well with efficacies of the H3N2
      influenza A component of the annual vaccine between 1971 and 2004, as do results
      of a theory of the immune response to influenza following vaccination. This new
      measure of antigenic distance is correlated with vaccine efficacy to a greater
      degree than are current state of the art phylogenetic sequence analyses or ferret
      antisera inhibition assays. We suggest that this new measure of antigenic
      distance be used in the design of the annual influenza vaccine and in the
      interpretation of vaccine efficacy monitoring.

PMID- 16460846
TI  - Formulation in tablets of a cholera whole cells inactivated vaccine candidate.
AB  - Licensed as well as candidate cholera vaccines available at the present requires
      the dose preparation (included buffer) at the moment of application. The aim of
      this work was to evaluate the presentation in oral tablets of an inactivated
      cholera vaccine to avoid that inconveniences during application. We have
      therefore compared inactivated cultures of Vibrio cholerae with tablets
      formulation vaccine. We obtained that antigenic activity (ELISA) and
      immunogenicity in animal model (ELISA and vibriocidal tests) of V. cholerae
      inactivated cell remained unaltered in the final tablet formulation. The results
      suggest that the oral tablet formulation could be a useful pharmaceutical form in
      order to produce a new and affordable cholera vaccine.

PMID- 16460847
TI  - A survey of indoor workplace radon concentration in Japan.
AB  - Radon ((222)Rn) concentration was measured at indoor workplaces in Japan to
      estimate effective dose to the public from (222)Rn and its progeny. Measurements
      were made from 2000 to 2003 at 705 sites in four categories of office, factory,
      school and hospital. Passive type Rn monitors equipped with two sheets of
      polycarbonate thin films for measuring radon concentrations were installed at
      observation sites and replaced every 3 months to observe seasonal variations in
      (222)Rn concentrations. The range of annual mean (222)Rn concentrations for all
      sites was 1.4-182 Bq m(-3), with the arithmetic mean and standard deviation were
      20.8 and 19.5 Bq m(-3). Annual mean (222)Rn concentration observed at office,
      factory, school and hospital were 22.6, 10.1, 28.4 and 19.8 Bq m(-3),
      respectively. Seasonal variations in (222)Rn concentrations at offices, schools
      and hospitals were similar to those found in dwellings, and variations in
      factories were similar to those found in outdoor environments. (222)Rn
      concentration observed in every quarter period was found to decrease as follows:
      school>office>hospital>factory. The average effective dose to the public due to
      (222)Rn was estimated to be 0.41 mSv y(-1) weighted by the working population.
      Considering the (222)Rn exposure in indoor workplaces, effective dose to the
      general public is estimated to be in the range from approximately 0.42 to 0.52
      mSv y(-1).

PMID- 16460848
TI  - Buccal corticotomy for removal of deeply impacted mandibular molars.

PMID- 16460849
TI  - Fixation of dicapitular fractures of the mandibular condyle with a headless bone
      screw.
AB  - The fixation of diacapitular fractures of the mandibular condyle utilising a
      headless cannulated bone screw (Martin HBS((R))) is described. An open approach
      was used with primary fixation of the fracture with a K-wire, over which the
      cannulated screw was inserted. The method and results are described.

PMID- 16460850
TI  - Use of a long saphenous vein patch graft to facilitate microvascular anastomosis
      when the carotid artery is stenosed.

PMID- 16460851
TI  - Re: The importance of preoperative assessment. Br J Oral Maxillofac Surg
      2005;43:440.

PMID- 16460852
TI  - The load-bearing characteristics of the forearm: pattern of axial and bending
      force transmitted through ulna and radius.
AB  - A biomechanical study was performed on 12 cadaveric arms to define the normal
      profiles of force transmission through the ulna and radius and demonstrate the
      effect on these of simulated injury of the distal radioulnar joint (DRUJ). Strain
      gauges were used to measure the axial and bending forces transmitted through each
      bone. Axial force transmitted through the ulna is, broadly, reciprocal to that
      seen in the radius, with the greatest force seen in supination. In all 12 arms,
      axial loading of the hand created an anterior bending force (to create a
      posterior convexity) in the distal radius. Axial loading of the hand created an
      anterior bending force in the distal ulna for half the specimens and a posterior
      bending force in the remaining half. Division and division with reconstruction of
      either the volar or the dorsal distal radioulnar ligament (DRUL) had no
      significant effect on force transmission through the ulna and radius, while
      excision of the ulnar head significantly disrupted the profiles of the axial and
      bending forces.

PMID- 16460854
TI  - Persistence of antibiotics such as macrolides, tiamulin and salinomycin in soil.
AB  - The extensive use of veterinary drugs in agriculture leads to contamination of
      manure. If this manure is used as fertiliser, soil may be exposed to the
      respective drugs. Additionally soil exposure may stem from contaminated sewage
      sludge that is used on some agricultural land as fertiliser. This study focuses
      on the fate of antibiotics in soil. We present a 120-day degradation experiment
      of six commonly used antibiotics: erythromycin, roxithromycin oleandomycin,
      tylosin, salinomycin and tiamulin in soil as well as calculating the resulting
      half-lives. The half-lives were 20 days for erythromycin, 27 days for
      oleandomycin, 8 days for tylosin, 16 days for tiamulin and 5 days for
      salinomycin; all according to 1st order kinetics. The concentration of
      roxithromycin remained nearly unchanged during the whole experiment.

PMID- 16460853
TI  - Seasonal profiles of leaf ascorbic acid content and redox state in ozone
      sensitive wildflowers.
AB  - Cutleaf coneflower (Rudbeckia laciniata L.), crown-beard (Verbesina occidentalis
      Walt.), and tall milkweed (Asclepias exaltata L.) are wildflower species native
      to Great Smoky Mountains National Park (U.S.A.). Natural populations of each
      species were analyzed for leaf ascorbic acid (AA) and dehydroascorbic acid (DHA)
      to assess the role of ascorbate in protecting the plants from ozone stress. Tall
      milkweed contained greater quantities of AA (7-10 micromol g(-1) fresh weight)
      than crown-beard (2-4 micromol g(-1) fresh weight) or cutleaf coneflower (0.5-2
      micromol g(-1) fresh weight). DHA was elevated in crown-beard and cutleaf
      coneflower relative to tall milkweed suggesting a diminished capacity for
      converting DHA into AA. Tall milkweed accumulated AA in the leaf apoplast (30-100
      nmol g(-1) fresh weight) with individuals expressing ozone foliar injury symptoms
      late in the season having less apoplast AA. In contrast, AA was not present in
      the leaf apoplast of either crown-beard or cutleaf coneflower. Unidentified
      antioxidant compounds were present in the leaf apoplast of all three species.
      Overall, distinct differences in antioxidant metabolism were found in the
      wildflower species that corresponded with differences in ozone sensitivity.

PMID- 16460855
TI  - Attention deficit hyperactivity disorder from a neurosciences and behavioral
      approach: an introduction.

PMID- 16460856
TI  - Uncertainties related to the assignment of a toxic equivalency factor for
      1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin.
AB  - The Toxic Equivalency Factor (TEF) approach is a methodology that assigns
      relative toxicity values to structurally related chemicals in comparison to a
      reference chemical. For the polychlorinated dibenzo-p-dioxins (PCDDs), the
      reference is the most potent congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). Here, we critically review the literature on the effects of a weak PCDD,
      1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD), and describe the uncertainties
      of assigning its TEF. PCDDs, including OCDD, are less potent in human cell models
      compared to the rat models from which the TEF are estimated. This lack of
      concordance is even more pronounced with the weaker congeners such as OCDD.
      Furthermore, OCDD is also likely to compete with TCDD for binding to cytochrome
      P4501A2 (CYP1A2), effectively decreasing the hepatic tissue/fat ratio of TCDD.
      Overall, the predictive value of TEFs would be improved by incorporating into
      this number the relative sensitivity of human cell responses compared to rodent
      responses, by determining the toxicological effects of altering the tissue
      distribution of dioxin-like compounds through competition for CYP-binding sites,
      and by understanding the mechanism of cancer causation of any dioxin and whether
      this mechanism is conserved in humans and at equivalent doses.

PMID- 16460857
TI  - Non-clinical development of cancer vaccines: regulatory considerations.
AB  - This paper discusses regulatory requirements essential during the non-clinical
      development of cancer vaccines. DNA vaccines and vaccines containing monoclonal
      antibodies are specifically addressed. ICH, CHMP, FDA, and WHO guidance documents
      in addition to scientific literature are reviewed and the regulatory framework,
      including respective EMEA and the FDA divisions responsible for review and
      assessment of cancer vaccines, is described. Selection criteria for an
      appropriate animal model for efficacy and/or toxicity studies are discussed.

PMID- 16460858
TI  - fMRI of parents of children with Asperger Syndrome: a pilot study.
AB  - BACKGROUND: People with autism or Asperger Syndrome (AS) show altered patterns of
      brain activity during visual search and emotion recognition tasks. Autism and AS
      are genetic conditions and parents may show the 'broader autism phenotype.' AIMS:
      (1) To test if parents of children with AS show atypical brain activity during a
      visual search and an empathy task; (2) to test for sex differences during these
      tasks at the neural level; (3) to test if parents of children with autism are
      hyper-masculinized, as might be predicted by the 'extreme male brain' theory.
      METHOD: We used fMRI during a visual search task (the Embedded Figures Test
      (EFT)) and an emotion recognition test (the 'Reading the Mind in the Eyes' (or
      Eyes) test). SAMPLE: Twelve parents of children with AS, vs. 12 sex-matched
      controls. DESIGN: Factorial analysis was used to map main effects of sex, group
      (parents vs. controls), and sexxgroup interaction on brain function. An ordinal
      ANOVA also tested for regions of brain activity where
      females>males>fathers=mothers, to test for parental hyper-masculinization.
      RESULTS ON EFT TASK: Female controls showed more activity in extrastriate cortex
      than male controls, and both mothers and fathers showed even less activity in
      this area than sex-matched controls. There were no differences in group
      activation between mothers and fathers of children with AS. The ordinal ANOVA
      identified two specific regions in visual cortex (right and left, respectively)
      that showed the pattern Females>Males>Fathers=Mothers, both in BA 19. RESULTS ON
      EYES TASK: Male controls showed more activity in the left inferior frontal gyrus
      than female controls, and both mothers and fathers showed even more activity in
      this area compared to sex-matched controls. Female controls showed greater
      bilateral inferior frontal activation than males. This was not seen when
      comparing mothers to males, or mothers to fathers. The ordinal ANOVA identified
      two specific regions that showed the pattern Females>Males>Mothers=Fathers: left
      medial temporal gyrus (BA 21) and left dorsolateral prefrontal cortex (BA 44).
      CONCLUSIONS: Parents of children with AS show atypical brain function during both
      visual search and emotion recognition, in the direction of hyper-masculinization
      of the brain. Because of the small sample size, and lack of age-matching between
      parents and controls, such results constitute a pilot study that needs
      replicating with larger samples.

PMID- 16460859
TI  - Bromate-induced ototoxicity.
AB  - For decades, it has been known that ingested potassium bromate and sodium bromate
      can induce hearing loss. Hearing loss onset, following high-dose ingestion, is
      generally rapid occurring within 4-16 h and of a severe to profound degree.
      Unlike the sensorineural hearing loss which is generally irreversible, bromate
      induced tinnitus, which is less well-studied, may reportedly be permanent or
      temporary. It is not clear whether actual bromate-induced vestibulotoxicity
      occurs in clinical populations. The primary sites of lesion for bromate-induced
      ototoxicity appear to be in the cochlea. However, possible effects on the VIIIth
      nerve and central auditory system have not been fully investigated. Based on
      animal studies, in the cochlea, bromate damages the stria vascularis, Reissner's
      membrane, inner and outer hair cells, Claudius cells and inner sulcus cells.
      Physiologically, bromate reduces the endocochlear potential, cochlear
      microphonics, and electrophysiologic auditory thresholds. Possible mechanisms are
      discussed. The effects of long-term low-dose bromate exposure on hearing have not
      been studied. These effects, if they occur, may not be readily detected in many
      clinical populations, because idiopathic hearing loss occurs commonly in the
      population as a whole. Further it is unknown whether or not chronic bromate
      ingestion may exacerbate noise-induced hearing loss. Further study to determine
      the maximum safe exposure level for long-term administration and to develop
      possible antidotes is warranted.

PMID- 16460860
TI  - Mutagenicity of bromate: implications for cancer risk assessment.
AB  - Bromate (BrO3-) is a rodent carcinogen that is formed as a drinking water ozone
      disinfection by-product and also used in some food and consumer products.
      Therefore, bromate is subject to assessment for its risk to humans. Because the
      selection of an appropriate model for conducting quantitative cancer risk
      assessment is based upon an understanding of the chemical's mode-of-action, it is
      necessary to determine whether the chemical is a mutagenic carcinogen. We present
      a review of the available information concerning the weight-of-the-evidence that
      bromate is a mutagenic carcinogen. The evidence indicates that bromate is
      mutagenic and that this activity is mediated by the formation of oxidative damage
      to the DNA, thus resulting in chromosomal damage. Not only does bromate induce
      genetic damage in vitro, it is also demonstrated to induce mutations in the
      kidney of exposed rats. This is significant because the rat kidney is one of the
      target tissues for tumor induction. While it is clear that bromate can cause
      damage in the target tissue, it is not clear whether bromate is a mutagenic
      carcinogen, that is, whether the observed tumors result from a mutagenic mode-of
      action. Further research is needed to clarify bromate's mode-of-action. However,
      in the absence of additional information, it is reasonable, based on an extensive
      database, to assume that bromate induces tumors via oxidative damage that causes
      chromosomal breakage.

PMID- 16460861
TI  - Construction and characterization of a bi-functional EGFP/sBAFF fusion protein.
AB  - A fusion between gene encoding fluoresce-enhanced green fluorescent protein
      variant (EGFP) and soluble domain of human B-cell-activating factor of the TNF
      family (sBAFF) was constructed and expressed in Escherichia coli. The EGFP/sBAFF
      had an apparent molecular weight of 45 kDa and was detected with anti-hsBAFF and
      anti-His(6) monoclonal antibodies. After being purified by immobilized metal
      affinity chromatography (IMAC), the fusion protein retained similar fluorescence
      spectra to those of EGFP. Biological activity assays showed the EGFP/sBAFF as
      well as sBAFF could co-stimulated human B lymphocyte proliferation in vitro. In
      addition, EGFP/sBAFF has shown specific binding to BAFF receptors positive-cells
      and the stained cells could be analyzed with flow cytometry. Thus, the fusion
      protein represents a readily obtainable source of biologically active sBAFF that
      may prove useful in further studies on BAFF and its receptors.

PMID- 16460862
TI  - An alternative intron-exon pairing scheme implied by unexpected in vitro
      activities of group II intron RmInt1 from Sinorhizobium meliloti.
AB  - RmInt1 is a mobile group II intron which interrupts ISRm2011-2, another mobile
      element from the bacterium Sinorhizobium meliloti. Ribozyme constructs derived
      from intron RmInt1 self-splice in vitro when incubated under permissive
      conditions, but the excised intron and ligated exons are largely replaced by
      unconventional products. These include a slightly shorter, 5'-end truncated 3'
      exon, truncated variants of the linear and lariat forms of the intron-3' exon
      reaction intermediate, as well as presumably circular molecules derived from the
      latter. Two factors explain the abundance of these products: (i) nucleotides 5-11
      of the 3' exon (IBS1*) provide a better match to the EBS1 5'-exon-binding site
      than the authentic IBS1 sequence in the 5' exon; (ii) exon ligation is unusually
      inefficient, and especially so when the 5' exon is truncated close to the second
      (IBS2) intron-binding site. We propose that reactions at the IBS1* site play a
      part in the regulation of the intron ISRm2011-2 host in vivo.

PMID- 16460863
TI  - The influence of gallium and other metal ions on the uptake of non-transferrin
      bound iron by rat hepatocytes.
AB  - BACKGROUND: Under conditions of iron overload non-transferrin-bound iron (NTBI)
      occurs in the circulation and is mainly cleared by the liver. Beside iron,
      gallium and aluminum enhance accumulation of NTBI. We try to characterize the
      mechanism and metal-mediated regulation of NTBI uptake using cultivated primary
      rat hepatocytes. METHODS: Hepatocytes from rat liver were incubated with 0.1
      mg/ml transferrin (as control), with ferric ammonium citrate or other di- and
      trivalent metal salts and the uptake of (55)Fe-labeled Fe-diethylene triammine
      pentaacetate was measured. RESULTS: Uptake rates for iron increased from 0.3 to
      2.1 pmol/mg protein per min in cells preincubated for 5 hours with 300 microM
      ferric ammonium citrate, to 1.7 pmol/mg protein per min with gallium and to 1.2
      pmol/mg protein per min with aluminum. Maximal stimulation was obtained with 300
      microM iron and 600 microM gallium. Preincubation with divalent metals was
      ineffective. NTBI uptake was specific for iron, partly inhibited by gallium
      citrate, diferric transferrin and completely inhibited by apotransferrin in
      control and gallium-treated cells. In iron-loaded cells, inhibition of NTBI
      uptake by diferric transferrin completely disappeared within 2 hours.
      CONCLUSIONS: These experiments show that hepatocytes do respond to the presence
      of trivalent metals by an increased transport capacity to sequester these ions.
      The metals seem to have at least partly different mechanisms of transport
      stimulation.

PMID- 16460864
TI  - The protein phosphatase 2A represents a novel cellular target for hepatitis C
      virus NS5A protein.
AB  - It is well established that HCV NS5A protein when expressed in mammalian cells
      perturbs the extracellular signal regulated kinase (ERK) pathway. The protein
      serine/threonine phosphatase 2A controls the phosphorylation of numerous proteins
      involved in cell signaling and one characterized function is the regulation of
      Ras-Raf mitogen activated protein (MAP) kinase signaling pathways. Our results
      showed that expression of HCV NS5A protein stimulates phosphatase 2A (PP2A)
      activity in cells, indicating the relevance of NS5A as a regulator of PP2A in
      vivo. We found that transient expression of the full length NS5A protein in
      different cell lines leads to a significant increase of the PP2A activity and
      this activity is specifically inhibited by the addition of okadaic acid, a PP2A
      inhibitor, in living cells. Further investigation showed that NS5A protein
      interacts in vivo and in vitro with the scaffolding A and the catalytic C
      subunits of PP2A. We propose that HCV NS5A represents a viral PP2A regulatory
      protein. This is a novel function for the NS5A protein which may have a key role
      in the ability of the virus to deregulate cell growth and survival.

PMID- 16460865
TI  - Resuscitation great: John Alexander MacWilliam.

PMID- 16460866
TI  - The effects of pre-arrest heparin administration dose for cardiac arrest model
      using extracorporeal lung and a heart assist (ECLHA) in dogs.
AB  - BACKGROUND AND PURPOSE: Clinical and experimental studies have shown that marked
      activation of blood coagulation occurs in cardiac arrest (CA) and cardiopulmonary
      resuscitation (CPR). Extracorporeal lung and heart assist (ECLHA) is applied in
      CA patients who cannot be rescued using conventional therapies. We hypothesized
      that the dose of heparin administered during the pre-arrest period would
      influence the outcome in a canine model of CA induced by 15 min of normothermia
      followed by ECLHA, which consists of heparin coating membrane lung and tubing. We
      therefore investigated the effects of two dose regimes of the pre-arrest heparin
      for this model. METHODS: Twelve mongrel female dogs were divided into two groups:
      a group given 200 U/kg heparin (H200, n=6) and a group given 700 U/kg heparin
      (H700, n=6), group during pre-arrest period. Normothermic ventricular
      fibrillation (VF) was induced in all dogs for 15 min, followed by 24h of ECLHA
      with rapidly induced mild hypothermia (33 degrees C) and 120 h of intensive care.
      Outcome evaluations included: (1) activated coagulation time (ACT); (2)
      catecholamine dose; (3) hematocrit (Hct) and platelet count; (4) survival rate;
      (5) neurological deficit scores (NDS); (6) postmortal macroscopic examination
      with the exception of the brain. RESULTS: In the H200 group, four dogs died of
      cardiogenic shock within 28 h. The autopsy revealed extensive patchy hemorrhages
      in the heart and intestine. In the H700 group, the amount of dopamine was
      significantly lower (6+/-10mg versus 75+/-41 mg, p<0.05) and the survival rate
      was significantly higher (100% versus 17%, p<0.05) than in the H200 group. The
      NDS at 120 h in the H700 group was 18+/-8% and the autopsy revealed an almost
      normal external appearance of the vital organs. There were no significant
      differences between groups in either the Hct and platelet count during the 24h of
      resuscitation, and no bleeding complications were observed. CONCLUSION: The use
      of ECLHA to resuscitate animals in prolonged CA may require a large dose of
      systemic heparin during the pre-arrest period even if ECLHA circuit was coated
      with heparin.

PMID- 16460867
TI  - Reduced cortical activity due to chronic low blood pressure: an EEG study.
AB  - Alterations in cortical activation processes due to chronic low blood pressure
      were investigated. In 40 hypotensive subjects and 40 normotensive controls, the
      contingent negative variation (CNV), induced by a constant foreperiod reaction
      time task, was assessed at nine scalp sites (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4).
      Additionally, spontaneous EEG was recorded at resting conditions. In
      hypotensives, a reduced amplitude of both the early and the late component of the
      CNV were found at Cz. At Fz the early CNV was reduced. Hypotensives exhibited
      longer reaction times, and the reaction time was negatively correlated with the
      CNV amplitude. Resting alpha power correlated negatively with blood pressure. The
      findings can be related to cognitive deficits due to hypotension found in earlier
      studies. The effects of hypotension on cortical activity are discussed to be
      mediated by afferents from the cardiovascular system to the prefrontal cortex as
      well as by reduced cerebral blood flow.

PMID- 16460868
TI  - Pregnancy outcome after early detection of bacterial vaginosis.
AB  - OBJECTIVE: To assess if detecting bacterial vaginosis either in early pregnancy
      or at midtrimester may predict adverse pregnancy outcome in women at risk for
      preterm delivery. STUDY DESIGN: 242 pregnant women with a previous preterm
      delivery were evaluated for bacterial vaginosis either in the first trimester
      (prior to 10+0 weeks) or in the second one (24-26 weeks). Adverse outcome was
      intended as miscarriage (< or =25 weeks), or premature delivery (< or =36+6).
      RESULTS: The risk of adverse pregnancy outcome was significantly increased in
      women diagnosed at first trimester with bacterial vaginosis (OR: 4.56; 95% CI:
      2.54-8.93); the same finding at midtrimester did not increase significantly the
      risk of preterm delivery. CONCLUSIONS: Early screening for bacterial vaginosis in
      pregnant women who experienced a preterm delivery may help in predicting the risk
      of adverse outcome.

PMID- 16460869
TI  - A critical analysis on Italian perinatal mortality in a 50-year span.
AB  - BACKGROUND: Perinatal mortality rate is used as an indicator of reproductive
      health worldwide. In western countries, national mortality registers are usually
      accurate and reliable. METHODS AND AIMS: We reviewed the data recorded in the
      past 50 years in Italy on perinatal and infant mortality. Each single class of
      mortality rate (according to WHO definitions) was assessed on temporal trends
      allowing a critical speculative analysis, mainly focusing on the last 20 years,
      in an attempt to evaluate the impact of prenatal diagnosis. RESULTS: Infant
      mortality rate (IMR) constantly decreased in the study period whereas early
      neonatal mortality rate progressively diminished in a 5-year comparison till the
      early 1990s. Perinatal mortality showed a linear negative trend until the 1980s,
      after which the decrease steadied at about 23% in the following 5-year period.
      Infant mortality attributable to congenital anomalies throughout a 20-year span
      (1980-2000) was steady at about 23% although a progressive reduction in general
      infant mortality was reported. CONCLUSIONS: A higher reduction in neonatal and
      perinatal mortality rate was found before the wide availability of the
      ultrasonographic prenatal diagnosis and the introduction of the law on voluntary
      abortion in Italy. Given these data, it seems that advances in neonatal care have
      improved the infant survival rates more than prenatal diagnosis, whereas
      obstetric care is linked to a reduction of the early perinatal mortality rate.

PMID- 16460870
TI  - Indices of insulin sensitivity, beta cell function and serum proinsulin levels in
      the polycystic ovary syndrome.
AB  - BACKGROUND: The study aim was to investigate the relationship between insulin
      resistance (IR), beta-cell function (betaF), hyperandrogenism and proinsulin
      levels during an oral glucose tolerance test (OGTT) in women with polycystic
      ovary syndrome (PCOS). METHODS: One hundred and twenty-six selected women were
      classified as follows: PCOS, BMI > 25 kg/m2 (n = 39); PCOS, BMI < 25 kg/m2 (n =
      54); controls, BMI > 25 kg/m2 (n = 14); controls, BMI < 25 kg/m2 (n = 19). Blood
      samples were collected between the third and sixth day of a spontaneous menstrual
      cycle, at 9:00 a.m., after an overnight fast. Serum levels of FSH, LH, PRL,
      17alpha-OH-progesterone, SHBG, testosterone, delta4-androstenedione, insulin,
      proinsulin and glucose were measured. A 75 g OGTT was performed, and
      concentrations of glucose, insulin and proinsulin were also measured at t = 30,
      60, 90, and 120 min. RESULTS: The markers of insulin secretion and the AUC for
      proinsulin were higher in obese and overweight women and in women with PCOS,
      respectively. The AUC for proinsulin was positively correlated with markers of
      IR, betaF and androgen levels. An inverse relationship between PI/I values and
      indices of IR and betaF was observed. CONCLUSIONS: Increased proinsulin levels
      reflect, most probably, insulin resistance, which is the key disorder in PCOS
      associated metabolic abnormalities. Beta-cell function, pre-proinsulin mRNA
      processing and proinsulin conversion to insulin could be initially increased as a
      result of IR. An interaction between circulating proinsulin and androgen
      biosynthesis or action might also exist.

PMID- 16460871
TI  - Recurrent endometrial cancer: a retrospective study.
AB  - OBJECTIVE: The value of follow-up after treatment for endometrial cancer will be
      discussed. STUDY DESIGN: We evaluated our clinical experience, including mode of
      detection, of patients with recurrent endometrial cancer treated in the Erasmus
      Medical Centre in Rotterdam over a 20-year period. Clinical data and
      histopathological features from 64 patients were analyzed. Survival was analyzed
      with a Kaplan-Meier curve. RESULTS: Twenty-two patients had a local recurrence,
      30 had a distant recurrence and 12 had simultaneous local and distant recurrent
      disease. Ninety-five percent of the local recurrences and 67% of the distant
      recurrences were detected within three years. Twenty-seven patients had a screen
      detected recurrence, 34 had an interval screening recurrence and two had a chance
      finding recurrence. The overall survival rate at two years was 70% and at five
      years 53%. Patients with a screen-detected recurrence had a 5-year survival rate
      of 62%, while patients with interval screening and chance finding recurrences had
      a 5-year survival rate of 47%. CONCLUSION: A follow-up program in the first three
      years after primary treatment of endometrial cancer is useful in detecting
      recurrent disease. We have no reason to use a different program of follow-up in
      patients with low risk primary disease.

PMID- 16460872
TI  - Jejuno-uterine fistula.

PMID- 16460873
TI  - The effect of progesterone, testosterone and synthetic progestogens on growth
      factor- and estradiol-treated human cancerous and benign breast cells.
AB  - OBJECTIVE: The effects of progesterone (P), testosterone (T), chlormadinone
      acetate (CMA), medroxyprogesterone acetate (MPA), norethisterone (NET),
      levonorgestrel (LNG), dienogest (DNG), gestodene (GSD) and 3-ketodesogestrel
      (KDG) were investigated in normal human breast epithelial MCF10A cells. In
      addition, the effects of these steroids were tested in estrogen and progesterone
      receptor positive HCC1500 human primary breast cancer cells. STUDY DESIGN: MCF10A
      cells were incubated with each progestogen at 1 microM and 100 nM for 7 days with
      growth factors epidermal growth factor (EGF), fibroblast growth factor (FGF) and
      insulin-like growth factor (IGF-I) (GFs, each 1 pM), and HCC1500 cells with GFs
      and/or estradiol (E2) 100 pM. Cell proliferation rate was measured by ATP-assay
      and cell death by photometric enzyme immunoassay. Ratios of cell
      death:proliferation were calculated. RESULTS: MPA and CMA with GFs induced
      proliferation of MCF10A cells. P, T, NET, LNG, DNG, GSD and KDG had no
      significant effect. In HCC1500 cells, MPA and CMA with GFs had an inhibitory
      effect compared to GFs alone. NET, LNG, DNG, GSD, KDG and T enhanced the
      proliferative effect of GFs. P had no significant effect. No progestogen could
      further enhance the stimulatory effect of E2 on HCC1500 cells; all but KDG
      inhibited it. MPA, GSD, T, CMA and NET had an anti-proliferative effect on the
      mitotic GF and E2 combination. P, LNG, DNG and KDG had no significant effect.
      CONCLUSIONS: Estrogens and mitogenic growth factors from stromal breast tissue
      are significant in growth-regulation of breast cells and may alter responses to
      progestogens. Certain progestogens are able to induce proliferation of or inhibit
      growth of benign or malignant human breast epithelial cells independently of the
      effects of growth factors and E2; therefore, choice of progestogen for hormone
      therapy may be important in terms of influencing possible breast cancer risk.

PMID- 16460874
TI  - Adsorption of synthetic homo- and hetero-oligodeoxynucleotides onto highly
      oriented pyrolytic graphite: atomic force microscopy characterization.
AB  - DNA adsorption on electrode surfaces is of fundamental interest for the
      development of DNA-based biosensors. The free adsorption of 10-mer synthetic
      oligodeoxynucleotides (ODNs) onto highly oriented pyrolytic graphite (HOPG)
      surfaces was studied using Magnetic AC mode atomic force microscopy (MAC Mode
      AFM). The mechanism of interaction of nucleic acids with carbon electrode
      surfaces was elucidated, using 10-mer synthetic homo- and hetero-ODNs sequences
      of known base sequences, because they allow clear interpretation of the
      experimental data. AFM images in air revealed different adsorption patterns and
      degree of HOPG surface coverage for the ODNs, and correlation with the individual
      structure and base sequence of each ODN molecule will be presented. The results
      demonstrated that the hydrophobic interactions with the HOPG hydrophobic surface
      explain the main adsorption mechanism, although other effects such as
      electrostatic and Van der Waals interactions may contribute to the free
      adsorption process. The ODNs interacted differently with the HOPG surface,
      according to the ODN sequence hydrophobic characteristics, being directly
      depending on the molecular mass, the hydrophobic character of the individual
      bases and on the secondary structure of the molecule. The importance of the type
      of base existent at the ODN chain extremities on the adsorption process was
      investigated and different adsorption patterns were obtained with ODN sequences
      composed by the same group of bases aligned in a different order.

PMID- 16460875
TI  - The validation of the patient perception of bladder condition (PPBC): a single
      item global measure for patients with overactive bladder.
AB  - OBJECTIVES: The purpose of this study was to evaluate the validity and
      responsiveness of a global measure for overactive bladder (OAB), the Patient
      Perception of Bladder Condition (PPBC). METHODS: Post-hoc analyses were conducted
      on two 12-wk clinical trials for OAB (Study 1: n = 865; Study 2: n = 520). In
      addition to the PPBC, patients completed two condition-specific health-related
      quality of life (HRQL) measures, the Overactive Bladder Questionnaire (OAB-q) and
      King's Health Questionnaire (KHQ), and bladder diaries at baseline and 12 wk.
      Validity of the PPBC was evaluated through correlations with baseline diaries,
      OAB-q, and KHQ. The responsiveness of the PPBC was evaluated using correlations
      and general linear models to assess the degree of association between change in
      PPBC and change in the diaries, OAB-q, and KHQ. RESULTS: Both samples were
      primarily women and white with mean ages of 61.0 and 58.8 yr. The majority of
      patients were incontinent (75.3% and 80.4%) with the greatest proportion of
      patients indicating that they had "moderate problems" (47.5% and 51.2%) on the
      PPBC at baseline. Significant correlations were present at baseline and among
      change scores between the PPBC and the bladder diaries (p < 0.001), OAB-q (p <
      0.001), and KHQ (p < 0.01). In both studies, patients with major PPBC improvement
      had significantly greater reductions in frequency, urgency episodes, incontinence
      episodes, and Symptom Bother and significantly greater improvements in HRQL than
      patients with only a minor PPBC improvement. CONCLUSION: The PPBC, a global
      patient-reported measure of bladder condition, demonstrated good construct
      validity and responsiveness to change. These findings support the use of the PPBC
      as a global assessment of bladder condition among patients with OAB.

PMID- 16460876
TI  - Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE)
      isoenzymes in the human prostate.
AB  - OBJECTIVES: With the introduction of sildenafil citrate (Viagra), the concept of
      phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of
      urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to
      be involved in the control of the normal function of the prostate. The aim of the
      present study was to evaluate by means of immunohistochemistry the expression and
      distribution of some cAMP- and cGMP-PDE isoenzymes in the prostate. MATERIAL &
      METHODS: Cryostat sections (10 microM) of formaldehyde-fixated tissue segments
      excised from the transition zone of human prostates were incubated with primary
      antibodies directed against the PDE isoenzymes 3, 4, 5, and 11. Then, sections
      were exposed to either fluorescein isothiocyanate- (FITC) or Texas Red- (TR)
      labeled secondary antibodies and visualization was commenced by means of laser
      fluorescence microscopy. RESULTS: TR-immunofluorescence indicating the presence
      of PDE4 (cAMP-PDE) was abundantly observed in the fibromuscular stroma as well as
      in glandular structures of the transition zone. In contrast to the distribution
      of PDE4, immunoactivity indicating PDE5 (cGMP-PDE) and 11 (dual substrate PDE)
      was mainly observed in glandular and subglandular areas. No immunostaining for
      PDE3 (cGMP-inhibited PDE) was detected. CONCLUSION: Our results confirm the
      presence of PDE isoenzymes 4, 5 and 11 in the transition zone of the human
      prostate and present evidence that these isoenzymes are not evenly distributed.
      These findings are in support of the hypothesis that there might be a rationale
      for the use of PDE inhibitors in the pharmacotherapy of BPH and LUTS.

PMID- 16460877
TI  - Review of second-order models for adsorption systems.
AB  - Applications of second-order kinetic models to adsorption systems were reviewed.
      An overview of second-order kinetic expressions is described in this paper based
      on the solid adsorption capacity. An early empirical second-order equation was
      applied in the adsorption of gases onto a solid. A similar second-order equation
      was applied to describe ion exchange reactions. In recent years, a pseudo-second
      order rate expression has been widely applied to the adsorption of pollutants
      from aqueous solutions onto adsorbents. In addition, the earliest rate equation
      based on the solid adsorption capacity is also presented in detail.

PMID- 16460878
TI  - Quantitative analysis of amyloid plaques in a mouse model of Alzheimer's disease
      by phase-contrast X-ray computed tomography.
AB  - Densely aggregated beta-amyloid peptides are believed to play a key role in the
      pathogenesis of Alzheimer's disease. Amyloid plaques are a potential target for
      molecular imaging to determine the clinical status of Alzheimer's disease. Phase
      contrast X-ray imaging combined with computed tomography is a promising technique
      that can be used to visualize the physical density of structures in biological
      tissues non-invasively, and without the use of imaging agents. Using brain tissue
      isolated from a mouse model of Alzheimer's disease, we show that beta-amyloid 40
      positive/beta-amyloid 42-positive amyloid plaques, but not beta-amyloid 40
      negative/beta-amyloid 42-positive amyloid plaques, exist as high-density
      aggregates that can be specifically detected by phase-contrast X-ray computed
      tomography. The phase-contrast X-ray computed tomography detected beta-amyloid 40
      positive/beta-amyloid 42-positive amyloid plaques in three-dimensions with an
      extremely high sensitivity comparable to that of histological analysis, and also
      enabled the load of amyloid plaques to be quantified. Furthermore, the use of
      phase-contrast X-ray computed tomography reveals that the physical density of
      beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques increases with
      age, and that the large volume, high-density, amyloid plaques that are
      specifically observed in aged Alzheimer's disease mice are closely associated
      with neuritic dystrophy. These results demonstrate that phase-contrast X-ray
      computed tomography is a highly sensitive imaging technique for analyzing dense
      cored amyloid plaques in postmortem samples, and is beneficial in elucidating
      amyloid pathophysiology in Alzheimer's disease.

PMID- 16460879
TI  - Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly
      and eliminates the acetylcholine satiety response.
AB  - Drinking a sugar solution on an intermittent schedule can promote sugar bingeing
      and cause signs of dependence while releasing dopamine repeatedly like a drug of
      abuse. It is hypothesized that sweet taste alone is sufficient for this effect in
      sucrose bingeing rats. On the theory that acetylcholine in the nucleus accumbens
      plays a role in satiety, it is further hypothesized that purging the stomach
      contents will delay acetylcholine release. Rats with gastric fistulas and nucleus
      accumbens guide shafts for microdialysis were fed 12 h each day. During the first
      hour, fistulas were open for the sham-feeding group and closed for the real
      feeding group, and 10% sucrose was the only food source. For the remaining 11 h,
      liquid rodent diet was available as well as the 10% sucrose to provide a balanced
      diet. In microdialysis tests during the first sugar meal on days 1, 2 and 21,
      extracellular dopamine increased at least 30% each day in both groups.
      Acetylcholine also increased during the sugar meals for the real-feeding animals,
      but not during sham feeding. In conclusion, the taste of sugar can increase
      extracellular dopamine in the nucleus accumbens without fail in animals on a
      dietary regimen that causes bingeing and sugar dependency. During sham feeding,
      the acetylcholine satiation signal is eliminated, and the animals drink more.
      These findings support the hypothesis that dopamine is released repeatedly in
      response to taste when bingeing on sweet food, and the acetylcholine satiety
      effect is greatly reduced by purging; this may be relevant to bulimia nervosa in
      humans.

PMID- 16460880
TI  - Developmental changes in the expression of calbindin and potassium-channel
      subunits Kv3.1b and Kv3.2 in mouse Renshaw cells.
AB  - One class of spinal interneurons, the Renshaw cells, is able to discharge at very
      high frequencies in adult mammals. Neuronal firing at such high frequencies
      requires voltage-gated potassium channels to rapidly repolarize the membrane
      potential after each action potential. We sought to establish the pattern of
      expression of calbindin and potassium channels with Kv3.1b and Kv3.2 subunits in
      Renshaw cells at different developmental stages of postnatal mice. The pattern of
      expression of calbindin changed dramatically during early postnatal development.
      An adult pattern of calbindin reactive neurons started to emerge from postnatal
      day 10 to postnatal day 14, with cells in laminae I and II of superficial dorsal
      horn and the ventral lamina VII. Renshaw cells were identified
      immunohistochemically by their expression of calbindin and their location in the
      ventral horn of the spinal cord. Western blot results of the lumbar spinal cord
      showed that Kv3.1b expression became faintly evident from postnatal day 10,
      reached a maximum at postnatal day 21 and was maintained through postnatal day
      49. Double labeling results showed that all Renshaw cells expressed Kv3.1b weakly
      from postnatal day 14, and strongly at postnatal day 21. Western blot results
      showed that Kv3.2 expression became detectable in the lumbar cord from postnatal
      day 12, and increased steadily until reaching an adult level at postnatal day 28.
      In contrast to the Kv3.1b results, Kv3.2 was not expressed in Renshaw cells,
      although some neurons located at laminae VIII and VI expressed Kv3.2. We conclude
      that Renshaw cells express Kv3.1b but not Kv3.2 from postnatal day 14.

PMID- 16460881
TI  - Induction of immediate early gene expression by high-frequency stimulation of the
      subthalamic nucleus in rats.
AB  - Deep brain stimulation is associated with delayed improvement of parkinsonian
      symptoms, such as hypokinesia with subthalamic nucleus stimulation, or dystonia
      with globus pallidus internus stimulation. The latency observed is better
      explained by molecular alterations than immediate electrophysiological processes,
      and clinical improvement may involve adaptive gene expression. Here, we have
      studied immediate early gene expression as fast molecular response to subthalamic
      nucleus stimulation. Bipolar electrodes were implanted bilaterally into the
      subthalamic nucleus of anesthetized male Wistar rats. High-frequency stimulation
      (130 Hz or 80 Hz, 60 micros, 300 microA) or low-frequency stimulation (5 Hz, 60
      micros, 300 microA) was performed with the right electrode for 15, 60, 120, and
      240 min whereas the silent left electrode served as negative control. Brains were
      fixed by transcardial perfusion and frozen sections were stained with polyclonal
      antibodies directed against three immediate early gene-encoded proteins, c-Fos, c
      Jun, and Krox-24 (NGFI-A, Egr-1, Zif268, Tis8, Zenk). After 120 and 240 h, c-Fos
      immunoreactivity was strongly upregulated in subthalamic nucleus neurons on the
      stimulated site. In contrast, no c-Fos immunoreactivity was detected on the non
      stimulated site except for single positive cells located in close proximity to
      the electrode tracks. Furthermore, c-Fos immunoreactivity was induced in
      subthalamic nucleus projection areas, such as primary and secondary motor cortex,
      primary somatosensory and insular cortex, lateral and medial globus pallidus,
      suprageniculate thalamic nucleus, pontine nuclei, medial geniculate nucleus, and
      substantia nigra. Similarly, c-Jun and Krox-24 were induced at the site of
      stimulation and in projection areas following high-frequency subthalamic nucleus
      stimulation. Whereas high frequency stimulation with 80 Hz was similarly
      effective none of the three immediate early gene-encoded proteins was induced
      with low-frequency stimulation (5 Hz) for 4 h. This is in accordance with the
      therapeutic effects of deep brain stimulation which are only elicited with high
      frequency stimulation. Our data provide evidence that immediate early gene
      expression in the subthalamic nucleus is rapidly and substantially induced by
      high-frequency stimulation. The induction of immediate early genes in projection
      sites suggests ipsilateral transsynaptic modulation of neuronal activity.

PMID- 16460882
TI  - Comparing web and mail responses in a mixed mode survey in college alcohol use
      research.
AB  - OBJECTIVE: This exploratory study examined potential mode effects (web versus
      U.S. mail) in a mixed mode design survey of alcohol use at eight U.S. colleges.
      METHODS: Randomly selected students from eight U.S. colleges were invited to
      participate in a self-administered survey on their alcohol use in the spring of
      2002. Data were collected initially by web survey (n=2619) and non-responders to
      this mode were mailed a hardcopy survey (n=628). RESULTS: College students who
      were male, living on-campus and under 21 years of age were significantly more
      likely to complete the initial web survey. Multivariate analyses revealed few
      substantive differences between survey modality and alcohol use measures.
      CONCLUSIONS: The findings from this study provide preliminary evidence that web
      and mail surveys produce comparable estimates of alcohol use in a non-randomized
      mixed mode design. The results suggest that mixed mode survey designs could be
      effective at reaching certain college sub-populations and improving overall
      response rate while maintaining valid measurement of alcohol use. Web surveys are
      gaining popularity in survey research and more work is needed to examine whether
      these results can extend to web surveys generally or are specific to mixed mode
      designs.

PMID- 16460883
TI  - Who drinks and why? A review of socio-demographic, personality, and contextual
      issues behind the drinking motives in young people.
AB  - The aim was to review the empirical research carried out over the last 15 years
      on the characteristics of young people (10- to 25-year olds) who have specific
      motives for drinking. In a computer-assisted search of relevant literature, 82
      studies were identified. Concerning demographic factors, a developmental trend
      was found - from general, undifferentiated drinking motives in late childhood and
      early adolescence to more gender-specific drinking motives in subsequent years.
      With regard to personality factors, two specific patterns can be distinguished:
      extraversion and sensation-seeking correlate with enhancement motives, while
      neuroticism and anxiety correlate most strongly with coping motives. For
      contextual factors, drinking motives were found to vary across countries but not
      among different ethnic groups in the same culture. Based on these results,
      preventive strategies should take into account general, undifferentiated drinking
      motivation in late childhood, and social and enhancement motives in adolescence,
      particularly among boys. Findings on personality indicate that it would be useful
      to focus on extraverted, sensation-seeking boys who drink for enhancement motives
      and neurotic, anxious girls who drink for coping motives.

PMID- 16460884
TI  - Hazardous or harmful alcohol use in Royal Australian Navy veterans of the 1991
      Gulf War: identification of high risk subgroups.
AB  - Elevated alcohol use disorders have been observed in 1991 Gulf War veterans from
      a variety of countries. This study used a self-report instrument, the Alcohol Use
      Disorders Identification Test (AUDIT), to ascertain whether any subgroups of 1232
      male Royal Australian Navy (RAN) Gulf War veterans were at higher risk of
      hazardous or harmful alcohol use. Recursive partitioning/classification and
      regression tree (CART) analysis, followed by logistic regression, found five
      subgroups among the veterans, with differing risks of AUDIT caseness. The highest
      risk subgroup comprised current smokers. The other two high risk groups both
      consisted of former or never smokers of lower rank who were (1) not married, or
      (2) married, with a current diagnosis of major depression. The above subgroups
      were over three times as likely to exhibit AUDIT caseness than those who were
      former or never smokers of higher rank. The findings have important implications
      for effective development of public health initiatives designed to encourage safe
      alcohol use among veterans.

PMID- 16460885
TI  - Interleukin-10 expression is positively correlated with oxidized LDL deposition
      and inversely with T-lymphocyte infiltration in atherosclerotic intimas of human
      coronary arteries.
AB  - The inflammatory balance modulated by pro- and anti-inflammatory cytokines in
      atherosclerotic lesions is still unclear. The purpose of this study was to
      investigate the immunohistochemical localization of interleukin-10 (IL-10) and
      the topographical correlation between IL-10-positive cells and the other
      inflammatory cells in human coronary arteries. Coronary arteries (242 sections)
      were obtained from 43 Japanese patients (mean age: 72+/-14 years) at autopsy, and
      the intimal changes were classified according to the classification of the
      American Heart Association. The immunohistochemical distributions of IL-10,
      oxidized low-density lipoprotein (oxLDL), macrophages, and lymphocytes were
      examined morphometrically. We compared the ratios of IL-10-positive
      cells/macrophages and T-lymphocyte number among the shoulder and in other areas
      of type IV lesions and in atherosclerotic lesion types. IL-10 was expressed
      mainly by macrophages, and the positive cell number increased as the lesions
      became advanced (p<0.0001). The number of IL-10-positive cells was positively
      correlated with that of oxLDL-positive cells, and inversely with infiltrating T
      lymphocytes (p<0.01). IL-10 expression in type IV-plaque shoulder was
      significantly lower than that in fibrous cap and the deeper portion under
      necrotic core (p<0.01). These findings suggest that IL-10 expression, seen mainly
      in macrophages, was possibly upregulated with oxLDL, and was inversely correlated
      with T-lymphocytic function in atherosclerotic coronary intimas.

PMID- 16460886
TI  - Effect of stimulus orderability and reinforcement history on transitive
      responding in pigeons.
AB  - Transitive responding in humans and non-human animals has attracted considerable
      attention because of its presumably inferential nature. In an attempt to
      replicate our earlier study with crows [Lazareva, O.F., Smirnova, A.A.,
      Bagozkaja, M.S., Zorina, Z.A., Rayevsky, V.V., Wasserman, E.A., 2004. Transitive
      responding in hooded crows requires linearly ordered stimuli. J. Exp. Anal.
      Behav. 82, 1-19], we trained pigeons to discriminate overlapping pairs of colored
      squares (A+ B-, B+ C-, C+ D-, and D+ E-). For some birds, the colored squares, or
      primary stimuli, were followed by a circle of the same color (feedback stimuli)
      whose diameter decreased from A to E (Ordered Feedback group); these circles were
      made available to help order the stimuli along a physical dimension. For other
      birds, all of the feedback stimuli had the same diameter (Constant Feedback
      group). In later testing, novel choice pairs were presented, including the
      critical BD pair. The pigeons' reinforcement history with Stimuli B and D was
      controlled, so that the birds should not have chosen Stimulus B during the BD
      test. Unlike the crows, the pigeons selected Stimulus B over Stimulus D in both
      ordered and Constant Feedback groups, suggesting that the orderability of the
      post-choice feedback stimuli did not affect pigeons' transitive responding. Post
      hoc simulations showed that associative models [Wynne, C.D.L., 1995.
      Reinforcement accounts for transitive inference (TI) performance. Anim. Learn.
      Behav. 23, 207-217; Siemann, M., Delius, J.D., 1998. Algebraic learning and
      neural network models for transitive and non-transitive responding. Eur. J. Cogn.
      Psychol. 10, 307-334] failed to predict pigeons' responding in the BD test.

PMID- 16460887
TI  - Spontaneous behavior of a rhesus monkey (Macaca mulatta) during memory tests
      suggests memory awareness.
AB  - Humans can predict with some accuracy whether or not they know the correct answer
      to a question before responding. In some cases the capacity to make such
      predictions depends on memory awareness, the ability to introspectively
      discriminate between knowing and not knowing. In this unplanned retrospective
      analysis of video taped behavior we asked whether a rhesus monkey's apparent
      frustration predicted his accuracy in a matching-to-sample task on a trial-by
      trial basis. The monkey was likely to aggressively strike the computer
      touchscreen when committing errors, whereas he generally touched the screen more
      gently when selecting the correct stimulus. This difference in behavior, which
      occurred before the monkey received feedback on the accuracy of his choice,
      suggests that he knew whether or not he remembered the correct response.

PMID- 16460888
TI  - Functional characterization of visual opsin repertoire in Medaka (Oryzias
      latipes).
AB  - A variety of visual pigment repertoires present in fish species is believed due
      to the great variation under the water of light environment. A complete set of
      visual opsin genes has been isolated and characterized for absorption spectra and
      expression in the retina only in zebrafish. Medaka (Oryzias latipes) is a fish
      species phylogenetically distant from zebrafish and has served as an important
      vertebrate model system in molecular and developmental genetics. We previously
      isolated a medaka rod opsin gene (RH1). In the present study we isolated all the
      cone opsin genes of medaka by genome screening of a lambda-phage and bacterial
      artificial chromosome (BAC) libraries. The medaka genome contains two red, LWS-A
      and LWS-B, three green, RH2-A, RH2-B and RH2-C, and two blue, SWS2-A and SWS2-B,
      subtype opsin genes as well as a single-copy of the ultraviolet, SWS1, opsin
      gene. Previously only one gene was believed present for each opsin type as
      reported in a cDNA-based study. These subtype opsin genes are closely linked and
      must be the products of local gene duplications but not of a genome-wide
      duplication. Peak absorption spectra (lambda(max)) of the reconstituted
      photopigments with 11-cis retinal varied greatly among the three green opsins,
      452 nm for RH2-A, 516 nm for RH2-B and 492 nm for RH2-C, and between the two blue
      opsins, 439 nm for SWS2-A and 405 nm for SWS2-B. Zebrafish also has multiple
      opsin subtypes, but phylogenetic analysis revealed that medaka and zebrafish
      gained the subtype opsins independently. The lambda and BAC DNA clones isolated
      in this study could be useful for investigating the regulatory mechanisms and
      evolutionary diversity of fish opsin genes.

PMID- 16460889
TI  - Evolution of ATP synthase subunit c and cytochrome c gene families in selected
      Metazoan classes.
AB  - To investigate the integrated evolution of mitochondrial and nuclear genomes in
      the eukaryotic cell, we have focused our attention on OXPHOS (oxidative
      phosphorylation) gene families which encode proteins involved in the main
      mitochondrial function. The present study reports the phylogenetic analysis of
      two OXPHOS gene families: ATP synthase subunit c (or lipid binding protein, LBP)
      and Cytochrome c (Cytc). Both gene families possess a higher expansion trend than
      the typically low duplication rate of OXPHOS genes in Metazoa, but follow a
      completely different evolutionary history, especially in mammals. LBP is
      represented by three well conserved isoforms in all mammals (P1, P2, P3): only P3
      possesses a clearly conserved isoform in all Vertebrates, P1 and P2 were already
      present before the bird-mammal divergence and there are preliminary evidence from
      the in silico analysis that P1, the most evolutionary divergent isoform, is
      poorly expressed and not regulated by NRF1. In contrast, Cytc family presents at
      least two duplicated genes in all the analysed Vertebrates, is subject to a high
      expansion trend, especially of processed pseudogenes in mammals, and some events
      of gain and loss of function can be supposed.

PMID- 16460890
TI  - Transcription of the Schizosaccharomyces pombe gene cdc18+: roles of MCB elements
      and the DSC1 complex.
AB  - In Schizosaccharomyces pombe, commitment to a round of DNA synthesis and entry
      into the cell cycle are dependent on the function of genes that are transcribed
      periodically during the cell cycle. Activation of these genes prior to S phase is
      primarily controlled through cis-acting elements known as MluI Cell-cycle Boxes,
      or MCBs, and by a family of transcription factors, including Cdc10, Res1, Res2
      and Rep2. These transcription factors are also known to be present in a complex,
      DSC1, that binds to the promoters of pre-S genes. We have demonstrated that
      within the promoter of cdc18+, a representative pre-S gene, the orientation and
      spacing of MCBs are crucial for activation and cell-cycle dependence. To our
      surprise, electrophoretic mobility shift assays showed a highly active mutant
      form of the promoter, which alters the spacing of the MCB elements, does not bind
      DSC1 but does bind a higher mobility complex. The binding of this second complex
      is not dependent on Cdc10 or the Res/Rep proteins. We conclude that, DSC1 binding
      does not correlate with cell-cycle dependent transcriptional activation, and the
      higher mobility species may represent a novel transcriptional activation complex
      that is also likely to function in pre-S transcription.

PMID- 16460891
TI  - Severe Streptococcus infection in spotted hyenas in the Ngorongoro Crater,
      Tanzania.
AB  - In a population of spotted hyenas (Crocuta crocuta) monitored between 1996 and
      2005 in the Ngorongoro Crater, Tanzania, 16 individuals from five of eight social
      groups displayed clinical signs of an infection, including severe unilateral
      swelling of the head followed by abscess formation at the mandibular angle,
      respiratory distress, mild ataxia, and lethargy. Two (12.5%) of these 16
      individuals died within days of developing signs. Clinical signs in hyenas were
      first noted in 2001, and most cases occurred between September 2002 and February
      2003, suggesting an outbreak of infection during this period. Histopathological
      examination of internal organs from one hyena that died with signs revealed
      morphological changes consistent with severe bacterial infection. Phenotypic
      examination and phylogenetic analysis of the 16S rRNA gene of the causative agent
      of infection revealed a Lancefield group C Streptococcus with a high level of
      homology to S. equi subsp. ruminatorum, a subspecies of S. equi recently
      described in domestic sheep (Ovis aries) and goats (Capra hircus) with mastitis
      in Spain. Strains similar to this bacterium were also isolated from two hyenas
      without obvious clinical signs, suggesting that hyenas may be 'carriers' of this
      bacterium, and from a sympatric Burchell's zebra (Equus burchelli), a herbivore
      species often consumed by hyenas. To our knowledge this is the first report of a
      Streptococcus infection in these two wildlife species. The high genetic
      similarity between the hyena and zebra isolates indicates that inter-specific
      transmission may occur, possibly when hyenas consume infected zebra carcasses.

PMID- 16460892
TI  - Streptozotocin (STZ) diabetes enhances benzo(alpha)pyrene induced renal injury in
      Sprague Dawley rats.
AB  - Information is lacking regarding the biological response to environmental
      chemicals in the context of pre-existing disease. Benzo(alpha)pyrene (BaP), a
      polycyclic aromatic hydrocarbon, is a byproduct of combustion that causes renal
      injury and elicits a nephropathic response. This study evaluated the
      nephrotoxicity of BaP in normoglycemic and diabetic rats. Female Sprague Dawley
      rats were divided into four groups: normoglycemic-vehicle (NV), normoglycemic-BaP
      (N-BaP), diabetic-vehicle (DV) and diabetic-BaP (D-BaP). Diabetes was induced by
      intraperitoneal (ip) injection of streptozotocin (60 mg/kg, 1 ml/kg). Rats were
      injected (ip) with vehicle or 10 mg/kg BaP (1 ml/kg) once per week for 5 weeks.
      Urinary protein and albumin, plasma creatinine and light microscopy were
      performed to assess the effects of BaP on kidney function. Diabetes was confirmed
      by plasma glucose levels >400 mg/dl in the DV and D-BaP groups. BaP increased
      kidney weight and blood urea nitrogen (BUN) levels in the D-BaP relative to the
      DV group. No change in BUN was observed following 5 weeks of BaP treatment in the
      normoglycemic animals, however, kidney weight was increased (p=0.013) in the N
      BaP relative to the NV animals. STZ diabetes increased susceptibility to BaP
      mediated renal damage following repeated treatment for 5 weeks when compared to
      age matched normoglycemic rats.

PMID- 16460893
TI  - QTL and candidate genes for fecundity in sows.
AB  - Fecundity in pigs is a trait of major economic interest but low heritability. For
      the improvement of fecundity, genetic markers for selection are desirable and
      therefore, several searches for genetic variation influencing fecundity have been
      performed. The aim of this review is to compare and to evaluate all published QTL
      analyses and candidate gene approaches concerning reproductive traits in sows.
      For this purpose, we present a comprehensive cytogenetic map comprising 54 QTL
      and 11 candidate genes with influence on reproductive traits. The evaluation and
      comparison of the results showed similarities, but also marked differences among
      studies. Reasons for different results are multicausal and are due to differences
      between resource populations, number of evaluated animals, mating systems,
      measured phenotypical traits and environmental influences. We could show that
      chromosome 8 and to a lower extend chromosome 7 are the most important
      chromosomes with regard to reproductive traits in pigs. For further research,
      fine mapping of the identified QTL regions is necessary in order to confirm and
      to narrow the most likely chromosomal intervals. Although difficult to perform,
      an advance would be a standardization of the experimental setup in particular, in
      respect to the collection of phenotypic data. Furthermore, we suggest to publish
      the information on further identified QTL and candidate genes as comprehensive
      and accurate as possible in order to allow a more transparent comparison and
      collation of the results.

PMID- 16460894
TI  - An in vitro study of the design and development of a novel doughnut-shaped
      minitablet for intraocular implantation.
AB  - A novel doughnut-shaped minitablet (DSMT) was developed and evaluated as a
      biodegradable intraocular drug delivery system for rate-modulated delivery of
      antiviral bioactives. The DSMT device was manufactured using a special set of
      punches fitted with a central-rod in a Manesty tableting press. The DSMT device
      released the antiretrovirals foscarnet and ganciclovir at a first-order rate. The
      erosion kinetics was assessed by gravimetric analysis and scanning electron
      microscopy. The device gradually eroded when immersed in simulated vitreous humor
      (SVH) (pH 7.4, 37 degrees C) and released bioactives in a sustained manner. The
      novel geometric design and veracity of the DSMT device was retained even after 24
      weeks of erosion. When considering the duration of the bioactive released from
      the DSMT device, it was found that by the careful selection of the type and
      concentration of polymer employed in formulating the DSMT device, it was possible
      to produce a device that could release drug for any period up to 12 months.

PMID- 16460895
TI  - T lymphocytes as potential therapeutic drug carrier for cancer treatment.
AB  - The aim of our research is the application of human immune cells (T lymphocytes)
      as target directed drug carrier. Thereby, the inclusion of therapeutical
      nanoparticles into immune cells is a new strategy for a localized chemotherapy.
      The autonomous targeting of diseased sites makes immune cells to perfectly
      controlled drug delivery systems. The study's aim was to demonstrate the
      feasibility to mobilise immune cells as therapeutic drug carrier systems which
      can be combined with existing immunotherapies. Therefore, Jurkat cells as well as
      T lymphocytes were used to identify the smoothest procedure for loading
      nanoparticles into immune cells. Different loading processes, incubation times
      and nanoparticle concentrations were compared. Nanoparticles coated with
      cytotoxic antibiotic doxorubicin were used in first release experiments. A time
      dependent liberation of doxorubicin from carrier cells was discussed as first
      therapeutic approach.

PMID- 16460896
TI  - A molecular genetic approach for species identification of mammals and sex
      determination of birds in a forensic case of poaching from South Korea.
AB  - DNA-based analysis was performed using partial mitochondrial cytochrome b genes
      of five mammalian specimens and Chromo-Helicase-DNA-binding (CHD) genes of five
      pheasants to determine whether specimens were from illegally hunted animals.
      Mammalian specimens were identified as being those of horse, roe deer, and cow
      through gene amplification using cytb981f and cytb981r primer set and sequencing.
      CHD genes were revealed to be those of three male and two female pheasants
      through polymerase chain reaction amplification. Because hunting of roe deers and
      female pheasants is prohibited in Korea, these results provided forensic
      evidences of illegal wild animal hunting.

PMID- 16460897
TI  - [ENVOL study on the medical management of varicella and its complications in
      French ambulatory care].
AB  - OBJECTIVE: The authors had for aim to describe the management of varicella and
      its complications in French ambulatory care. METHODS: A descriptive prospective
      national survey was carried out in France on patients visiting a random sample of
      French GPs and pediatricians (investigators) having diagnosed varicella. During
      an inclusion period of 4 months, the investigators enrolled all patients (adults
      children) who presented with varicella or varicella related complications, and
      who had not previously visited the investigator for this episode. Three
      questionnaires were used to record the data. RESULTS: One thousand two hundred
      patients were enrolled by 393 physicians 75% of whom were GPs. Ninety-four
      percent of patients were children under 13 years of age (group I). The sex ratio
      (M/F) was 1.1. The mean age was 3.5 years in group I and 23.8 years in patients
      over 13 years of age (group II). The mean length of the varicella episode was
      about 10.7 days. Most patients were given a pharmaceutical prescription on
      inclusion, 1% were also prescribed medical procedures, 0.3% were given local
      treatment, and 0.09% underwent physical therapy sessions. A proportion of 12.6%
      of patients visited their physician twice or more for the same episode. Six group
      I children were hospitalized. Eighty-seven patients presented with at least one
      complication i.e. 7.8% (95%CI=6.3-9.3) of all episodes, mainly bacterial
      superinfections. CONCLUSIONS: The rate of complications associated with varicella
      infection was higher than usually reported in France but in the same order of
      magnitude as in other developed countries. Bacterial superinfections were found
      to be the most frequent complications of varicella.

PMID- 16460898
TI  - Single-stranded conformational polymorphism for separation of mixed rRNAS (rRNA
      SSCP): a new method for profiling microbial communities.
AB  - We show that non-denaturing gel electrophoresis, or single-stranded
      conformational polymorphism (SSCP), can be used to separate mixtures of full
      length rRNAs. Individual bands can then be excised for identification by RT-PCR
      and sequencing. This has the advantage over profiling methods such as DGGE and T
      RFLP that no PCR amplification is involved prior to sequencing; thus, extraction
      biases aside, it should yield a quantitative picture of community composition in
      terms of ribosome content. To simplify banding patterns, RNA subsamples (e.g.
      bacterial 16S rRNA) can first be isolated by magnetic bead capture hybridization.
      Alternatively, oligonucleotide-directed ribonuclease H (RNase H) digestion can be
      used to identify bands of interest by running digested samples in parallel to
      undigested ones. We illustrate the use of this technique to identify a
      potentially predominant species in a hypersaline microbial mat. We anticipate
      that rRNA-SSCP will be useful for community profiling; for clone library
      construction by directed cloning of individual rRNAs; and for following
      incorporation of radiolabeled substrates at the species level, by gel
      autoradiography, without advance information or guesswork about which species
      might be active and abundant.

PMID- 16460899
TI  - Determination of vinflunine in rat plasma by liquid chromatography-electrospray
      ionization mass spectrometry for a pharmacokinetic study.
AB  - A rapid, simple and sensitive high-performance liquid chromatography-electrospray
      ionization mass spectrometry (LC-ESI-MS) method for the quantification of
      vinflunine in rat plasma was developed and validated. After making alkaline with
      NaOH, plasma was extracted with ethyl acetate and determined by LC-MS. The
      analysis was carried out on a Shimadzu VP-ODS column (150 mmx4.6 mm ID, packed
      with 5 microm C18 Silica RP particle). The mobile phase consisted of methanol-10
      mM ammonium acetate buffer (80:20, v/v) with the flow rate of 1.0 ml/min. LC-MS
      was performed in the selected ion monitoring (SIM) mode using target ions at m/z:
      817.3 for vinflunine and m/z: 373.2 for finasteride (IS). Chromatographic
      separation was achieved in less than 6 min and the calibration curve was linear
      over a concentration range of 0.025-6.25 microg/ml. The intra-assay and inter
      assay variability values were less than 8.6%. The accuracy ranged from 91.5 to
      105.6%. The established method has been successfully applied to a pharmacokinetic
      study of vinflunine in rats.

PMID- 16460900
TI  - Determination of plant and enterolignans in human serum by high-performance
      liquid chromatography with tandem mass spectrometric detection.
AB  - An HPLC-MS/MS method was validated for the determination of the plant lignans 7
      hydroxymatairesinol (HMR), matairesinol (Mat), secoisolariciresinol (Seco),
      lariciresinol (Lar), and cyclolariciresinol (CLar) and for the enterolignans 7
      hydroxyenterolactone (HEL), enterodiol (ED), and enterolactone (EL) in human
      serum. The method included sample enzymatic hydrolysis, solid-phase extraction,
      and lignan analysis using a triple quadrupole mass spectrometer with electrospray
      ionisation in the multiple-reaction monitoring mode. The serum lignans were
      quantified using deuterated Mat or EL as internal standards. The method met the
      validation criteria for selectivity, intra- and inter-assay precision, and
      accuracy. The method was applied to ten serum samples collected from healthy
      individuals (five men and five women) consuming their habitual Finnish diet. All
      lignans except HMR and Seco were found in quantifiable amounts in the samples.
      All serums contained EL; the average concentration was 34 nM. In three
      individuals, the serum concentration of plant lignans was higher than that of
      enterolignans. Using the method, common dietary plant lignans and their major
      metabolites can be reliably quantified in human serum at low-nanomolar
      concentrations in a simple and rapid way.

PMID- 16460901
TI  - Prediction of the permeability of drugs through study on quantitative structure
      permeability relationship.
AB  - This study is to research the quantitative structure-permeability relationship of
      20 drugs having similar structure. Permeability was determined by using the Caco
      2 cell in vitro model. The apparent permeability coefficient (Papp) of each drug
      both of apical to basolateral side and basolateral to apical side was measured at
      the concentration corresponding to 0.1 times the highest dose strength of 250 mL
      dissolved buffer. In order to test the permeability system suitability, we
      measured the Papp of 19 model drugs out of 20 which presented in 'Waiver of In
      Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral
      Dosage Forms based on the Biopharmaceutics Classification System' of FDA
      guidance. Also, we demonstrated the functional expression of efflux systems
      (e.g., p-gp) by bi-directional transport studies with rhodamine 123. Also, as a
      result of the study on quantitative structure-permeability relationship by using
      the partial least square method, it was possible to predict the permeability of
      drugs from their 3D structure. The quantitative structure-permeability
      relationship provided a cross-validated q2=0.789, a normal r2=0.998. Considering
      all of above results, analysis on this quantitative structure-permeability
      relationship appears to be a very useful tool to predict the permeability.

PMID- 16460902
TI  - Analysis of Amaryllidaceae alkaloids from Narcissus by GC-MS and capillary
      electrophoresis.
AB  - Amaryllidaceae are known as ornamental plants, furthermore some species of this
      family contain galanthamine, an acetylcholinesterase inhibitor approved for the
      treatment of Alzheimer's disease, and other alkaloids with interesting
      pharmacological activity. In the present work, the quali- and quantitative
      analysis of Amaryllidaceae-type alkaloids in the bulbs of Narcissus species is
      presented using different analytical approaches. Extracts of Narcissus
      pseudonarcissus cv. Carlton and Narcissus jonquilla Quail, were first examined by
      GC-MS using a Rtx-5 MS (programmed temperature) and the major alkaloids were
      identified. Together with galanthamine, high contents of haemanthamine, were
      found. Galanthamine was reliably quantified by GC-MS, whereas haemanthamine
      partly decomposed under the GC conditions, thus alternative analytical methods
      were investigated. Firstly, reversed-phase HPLC-ESI-MS was applied to identify
      and isolate at semipreparative levels haemanthamine. The compound was fully
      characterized by MS/MS and (1)H NMR and then used as a reference substance. The
      quantitation of both galanthamine and haemanthamine was then accomplished by
      capillary electrophoresis with spectrophotometric detection. A non-aqueous (NACE)
      approach was selected in order to use a running buffer fully compatible with
      samples in organic solvent. In particular, a mixture methanol-acetonitrile
      (75:25, v/v) containing ammonium acetate (90 mM) was used as a background
      electrolyte. The same analytical sample was subjected to GC-MS and NACE analysis;
      the different selectivity displayed by these techniques allowed different
      separation profiles that can be useful in phytochemical characterization of the
      extracts. The GC-MS and NACE methods were validated and applied to the
      quantitation of galanthamine (GC-MS and NACE) and haemanthamine (NACE) in bulbs
      of N. jonquilla.

PMID- 16460903
TI  - Anisoin: a useful pre-chromatographic derivatization fluorogenic reagent for LC
      analysis of guanidino compounds.
AB  - The use of anisoin as pre-chromatographic reagent for LC analysis of guanidino
      compounds is proposed. The reagent reacts (5 min at 100 degrees C) with guanidino
      function and the resulting adducts can be chromatographed under reversed-phase
      conditions. A fluorescence detector (lambda(ex)=325 nm; lambda(em)=435 nm) was
      used to detect guanidino adducts. The derivatization and chromatographic
      conditions were optimised by a series of experiments. Application to the
      determination of arginine and creatine in pharmaceuticals and arginine,
      guanidine, methylguanidine, guanidinosuccinic acid, beta-guanidinopropionic acid,
      gamma-guanidinobutyric acid, guanidinoacetic acid and homoarginine in human urine
      is described. Quantitation limits ranged from 6 to 30 fmol, except for creatine
      (510 fmol).

PMID- 16460905
TI  - Positive correlation of serum bio-intact PTH(1-84) but not intact PTH with
      parathyroid gland size in hemodialysis patients.
AB  - To evaluate the usefulness of newly-developed bio-intact parathyroid hormone (Bio
      PTH) assay, which measures exclusively intact PTH(1-84) molecule, serum PTH level
      determined by Bio-PTH assay, in comparison with second-generation intact PTH (I
      PTH) assay, was examined for its correlation with parathyroid gland size. Serum
      PTH was determined in 46 male HD patients, together with bone formation markers
      bone alkaline phosphatase, intact osteocalcin, N-terminal propeptide of type I
      collagen, and bone resorption markers deoxypyridinoline, pyridinoline, beta
      crossLaps. Maximal diameter of parathyroid gland was determined with
      ultrasonography as the parathyroid gland size. Serum Ca and Pi correlated
      significantly with parathyroid gland size rationalizing our method to define
      parathyroid gland size. Serum Bio-PTH was correlated significantly in a positive
      manner with parathyroid gland size (R = 0.308, P = 0.0474), whereas serum I-PTH
      did not. Furthermore, parathyroid gland size did not exhibit a significant
      correlation with any of bone formation markers or bone resorption markers. The
      lack of correlation between bone markers and parathyroid gland size in HD
      patients may be explained by the occurrence of refractoriness of bone to PTH. In
      conclusion, serum Bio-PTH assay could provide a better assay than I-PTH assay to
      estimate parathyroid function in HD patients, due mainly to its exclusive
      correlation with parathyroid gland size.

PMID- 16460906
TI  - Fear of needles and vasovagal reactions among phlebotomy patients.
AB  - Anxiety associated with blood and injections is a common problem in medical
      settings and, in severe cases, affects sufferers' ability to receive medically
      essential treatment. The present study was conducted to examine incidence of
      adverse reactions to venipunctures among phlebotomy patients, as well as to
      understand the demographic and psychological characteristics associated with such
      reactions. A large sample of participants undergoing venipuncture (N=3315) was
      recruited from hospital-based phlebotomy laboratories. Participants completed a
      brief questionnaire assessing psychological and physiological reactions to having
      their blood drawn. Results indicated that a small minority of patients
      experienced significant anxiety symptoms during venipuncture. Vasovagal reactions
      and vasovagal syncope were extremely infrequent. A tendency to experience pain,
      disgust, and fear of fainting during injections was associated with anxious
      responding to the venipuncture and a probable diagnosis of needle phobia.
      Theoretical and practical implications are discussed.

PMID- 16460907
TI  - Human KLF17 is a new member of the Sp/KLF family of transcription factors.
AB  - The Sp/KLF transcription factors perform a variety of biological functions, but
      are related in that they bind GC-box and CACCC-box sequences in DNA via a highly
      conserved DNA-binding domain. A database homology search, using the zinc finger
      DNA-binding domain characteristic of the family, has identified human KLF17 as a
      new family member that is most closely related to KLFs 1-8 and 12. KLF17 appears
      to be the human orthologue of the previously reported mouse gene, zinc finger
      protein 393 (Zfp393), although it has diverged significantly. The DNA-binding
      domain is the most conserved region, suggesting that both the murine and the
      human forms recognize the same binding sites in DNA and may retain similar
      functions. We show that human KLF17 can bind G/C-rich sites via its zinc fingers
      and is able to activate transcription from CACCC-box elements. This is the first
      report of the DNA-binding characteristics and transactivation activity of human
      KLF17, which, together with the homology it displays to other KLF proteins, put
      it in the Sp/KLF family.

PMID- 16460908
TI  - Comparative genomic organization of the human and bovine PRNP locus.
AB  - We sequenced a 208-kb BAC clone spanning the bovine prion protein (PRNP) locus,
      and compared the genomic structure with that of human. As a result, we determined
      the precise breakpoint between the two syntenic genomes, located on the 5' UTR of
      the PRNP gene, and discovered two highly repetitive sequences near the
      breakpoint. Further analysis demonstrated that the genomic structure of three
      genes, PRNP, PRND, and RASSF2, within the syntenic region of the bovine genome is
      highly conserved in order and orientation. The PRNT locus was not found in bovine
      but is conserved in several primates, including human. Moreover, we confirmed
      that the bovine RASSF2 is composed of 10 exons, as is the human gene, showing
      some difference from a previous report. Our findings may provide useful clues for
      understanding the evolutional process in the PRNP locus and also the mechanism
      that allows TSE from cattle to infect humans.

PMID- 16460909
TI  - Excitement over the chemistry of immune-nervous system relationships.

PMID- 16460910
TI  - Specific detection of enterovirus 71 directly from clinical specimens using real
      time RT-PCR hybridization probe assay.
AB  - Enterovirus 71 (EV71) is one of the main causative agents of hand, foot and mouth
      disease (HFMD) in young children. Infections caused by EV71 could lead to many
      complications, ranging from brainstem encephalitis to pulmonary oedema, resulting
      in high mortality. Thus, rapid detection of the virus is required to enable
      measures to be implemented in preventing widespread transmission. Based on
      primers and probes targeting at the VP1 region, a real-time reverse-transcriptase
      polymerase chain reaction (RT-PCR) hybridization probe assay was developed for
      specific detection of EV71 from clinical specimens. Quantitative analysis showed
      that the assay was able to detect as low as 5 EV71 viral copies and EV71 was
      detected from 46 of the 55 clinical specimens obtained from pediatric patients
      suffering from HFMD during the period from 2000 to 2003 in Singapore. This study
      showed that the single tube real-time RT-PCR assay developed in this study can be
      applied as a rapid and sensitive method for specific detection of EV71 directly
      from clinical specimens.

PMID- 16460911
TI  - A Bartonella vinsonii berkhoffii typing scheme based upon 16S-23S ITS and Pap31
      sequences from dog, coyote, gray fox, and human isolates.
AB  - Since the isolation of Bartonella vinsonii subspecies berkhoffii from a dog with
      endocarditis in 1993, this organism has emerged as an important pathogen in dogs
      and as an emerging pathogen in people. Current evidence indicates that coyotes,
      dogs and gray foxes potentially serve as reservoir hosts. Based upon sequence
      differences within the 16S-23S ITS region and Pap31 gene, we propose a
      classification scheme that divides B. vinsonii subsp. berkhoffii isolates into
      four distinct types. Two conserved sequences, of 37 and 18 bp, respectively, are
      differentially present within the ITS region of each of the four B. vinsonii
      subsp. berkhoffii types. To date, B. vinsonii berkhoffii types I, II, and III
      have been identified in the US, type III in Europe and type IV in Canada. Based
      upon the proposed genotyping scheme, the geographic distribution of B. vinsonii
      berkhoffii types needs to be more thoroughly delineated in future molecular
      epidemiological studies involving Bartonella infection in coyotes, dogs, gray
      foxes, human beings and potentially other animals or in arthropod vectors. Strain
      typing may help to better define the reservoir potential, carriership patterns,
      modes of transmission, and geographic distribution for each B. vinsonii
      berkhoffii type.

PMID- 16460912
TI  - Multiplex PCR-RFLP methods for pfcrt, pfmdr1 and pfdhfr mutations in Plasmodium
      falciparum.
AB  - Plasmodium falciparum drug resistance is a major factor for the death toll of
      malaria. Resistance has been associated with specific single nucleotide
      polymorphisms (SNPs) in the parasite genes pfmdr1 (N86Y) and pfcrt (K76T)
      associated with quionoline antimalarial resistance, and pfdhfr (N51I, C59R,
      S108N) correlated with resistance of the antifolate combination sulfadoxine
      pyrimethamine. These SNPs constitute the basis for the surveillance of drug
      resistance through high sensitive molecular methods in malaria endemic countries.
      In this work, we developed a multiplex PCR-RFLP protocols for the diagnosis of
      these molecular markers, leading to significant decreases in reagent costs, time,
      number of manipulations and hence human resources.

PMID- 16460913
TI  - Dendrimer FISH detection of single-copy intervals in acute promyelocytic
      leukemia.
AB  - Acute promyelocytic leukemia (AML-M3) is characterized by a translocation between
      chromosomes 15 and 17 [t(15;17)]. The detection of t(15;17) at the single cell
      level, is commonly done by fluorescence in situ hybridization (FISH) using
      recombinant locus specific genomic probes greater than 14 kilobases kb in length.
      To allow a more thorough study of t(15;17), we designed small (0.9-3.6 kb),
      target-specific, single-copy probes from the human genome sequence. A novel
      detection approach was evaluated using moieties possessing more fluorophores, DNA
      dendrimers (up to 375 fluorophores per dendrimer). Two detection approaches were
      evaluated using the dendrimers: (1) dendrimers modified with anti-biotin
      antibodies for detection of biotinylated bound probes, and (2) dendrimers
      modified with 45-base long oligonucleotides designed from the single-copy probes,
      for direct detection of the target region. The selectivity of the probes was
      confirmed via indirect labeling with biotin/digoxigenin by nick translation, with
      detection efficiencies between 50 and 90%. Furthermore, the scFISH probes were
      successfully detected on metaphase cells with anti-biotin dendrimer conjugates
      and on interphase cells with 45-base modified dendrimers. Our results bring up
      the possibility to detect target regions of less than 1 kb, which will be a great
      contribution to high-resolution analysis of genomic sequences.

PMID- 16460914
TI  - Signaling through ERBB receptors: multiple layers of diversity and control.
AB  - The four known ERBB receptors in humans are involved in a broad range of cellular
      responses, and their deregulation is a significant aspect in a large number of
      disease states. However, their mechanism of action and modes of control are still
      poorly understood. This is largely due to the fact that the control of ERBB
      activity is a multilayered process with significant differences between the
      various ERBB members. In contrast to other receptor tyrosine kinases, the kinase
      domain of EGFR (ERBB1) does not require phosphorylation for activation.
      Consequently, the overall activation state of the receptor is controlled by
      constant balancing of activity favoring and activity suppressing actions within
      the receptor molecule. Influences of the membrane microenvironment and context
      dependent interactions with varying sets of signaling partners are superimposed
      on this system of intramolecular checks and balances. We will discuss current
      models of the control of ERBB signaling with an emphasis on the multilayered
      nature of activation control and aspects that give rise to diversity between ERBB
      receptors.

PMID- 16460915
TI  - Postmortem brain calcineurin protein levels in schizophrenia patients are not
      different from controls.
AB  - Calcineurin (CaN), also designated as protein phosphatase 2B, is a major
      Ca2+/calmodulin-binding protein in the brain and the only serine/threonine
      phosphatase under the control of Ca2+/calmodulin. CaN activity has been
      implicated in downstream regulation of dopaminergic signal transduction and in
      NMDA receptor-dependent synaptic plasticity. Thus, it serves as a point of
      convergence for the abnormalities of these two neurotransmitter systems in
      schizophrenia. The aim of the present study was to determine if levels of CaN
      were altered in two schizophrenia- and CaN-related brain regions--the
      dorsolateral prefrontal cortex and hippocampus from subjects with schizophrenia
      compared to that in tissue from age and sex matched controls. CaN protein levels
      were measured by Western-blot analysis in samples from 15 schizophrenia patients
      vs. 15 control subjects. No significant differences in CaN protein levels were
      found either in the prefrontal cortex or in the hippocampus of schizophrenia
      patients compared to matched control subjects. Our result of lack of difference
      does not support the concept that brain CaN levels are a pathophysiological
      factor in this disorder. Further studies with antibodies against specific CaN
      catalytic subunit isoforms (presently unavailable) are required to resolve this
      issue.

PMID- 16460916
TI  - Suicide behaviour over 18 months in recent onset schizophrenic patients: the
      effects of CBT.
AB  - The results of a trial of cognitive behaviour therapy, supportive counselling and
      treatment as usual in recent onset schizophrenia on suicide behaviour are
      reported. Treatment was delivered over a five week period during hospitalisation
      for an acute episode. Participants were assessed at baseline, 6 weeks, 3 and 18
      months. Over the 18 months there were 3 definite suicides and 2 deaths by
      accidental causes. The rates of moderate to severe suicidal behaviour were 13% at
      admission, 4% at six weeks, 1.5% at three months and 6% at 18 months. There were
      no beneficial or adverse effects of psychological treatment on suicide behaviour
      that reduced significantly with clinical recovery. There is a general picture of
      those who suffer persistently higher levels of psychotic symptoms, poorer
      functioning, depression and low self-esteem have higher severity of suicide
      behaviour, although the numbers with clinically significant suicide behaviour are
      low. CBT may need to be modified to directly target suicide behaviour and its
      antecedents to significantly reduce risk; recommendations on this are made.

PMID- 16460917
TI  - A 12-month prospective follow-up study of patients with schizophrenia-spectrum
      disorders and substance abuse: changes in psychiatric symptoms and substance use.
AB  - While it is widely known that patients with schizophrenia-spectrum psychoses and
      co-occurring substance use disorders are more difficult to manage, there is
      limited data on the course of their psychiatric symptoms when they remain in
      treatment over time. This prospective 12-month study evaluated changes in
      psychiatric symptoms and substance use to ascertain if the co-existence of
      substance use disorders influences ratings of psychiatric symptoms at follow-up.
      147 outpatients in a continuing care program were assessed at intake and followed
      prospectively for 12 months. Psychiatric symptoms were measured at baseline and
      12-month follow-up using the Positive and Negative Syndrome Scale (PANSS) and
      Hamilton Depression Rating Scale (HAM-D). Subjective psychological distress was
      rated with the Brief Symptom Inventory (BSI) and quality of life by the
      Satisfaction with Life Domains Scale (SDLS). Drug and alcohol use was measured
      with the Addiction Severity Index (ASI). 50.3% of patients were diagnosed with
      dual disorders (DD) (current and lifetime). The most common primary substances of
      abuse were alcohol (35.6%) and cannabis (35.1%). DD subjects had higher baseline
      PANSS positive scores but experienced a greater reduction at 12 months compared
      to single diagnosis (SD) patients. Severity of substance abuse as measured by ASI
      composite scores did not decrease significantly between baseline and 12 months.
      DD patients with schizophrenia and related psychoses treated for their
      psychiatric illness showed a reduction in PANSS scores over 12 months, even when
      their substance use remained largely unchanged. However, co-morbidity cases
      continued to show higher depression and anxiety ratings. Ongoing substance abuse
      appears to be related to levels of depression as 62.5% of DD-current versus 34.7%
      of SD patients had HAM-D scores in the depressed range at 12-month follow-up.
      Implications for treatment are discussed.

PMID- 16460918
TI  - A prospective evaluation of adherence to medication in first episode
      schizophrenia.
AB  - The aim of this study was to identify the features of first episode schizophrenia
      that predict adherence antipsychotic medication at six-month follow-up. We used
      validated instruments to assess clinical and socio-demographic variables in all
      patients with first episode schizophrenia from a defined geographical area
      admitted to a Dublin psychiatric hospital over a four-year period (N=100). At six
      month follow-up (N=60) we assessed adherence to medication using the Compliance
      Interview. One third of patients with schizophrenia were non-adherent with
      medication within six months of their first episode of illness. High levels of
      positive symptoms at baseline, lack of insight at baseline, alcohol misuse at
      baseline and previous drug misuse predict non-adherence. These results indicate
      that an identifiable subgroup of patients with first episode schizophrenia is at
      high risk of early non-adherence to medication. While high positive symptom
      scores pre-date and predict non-adherence in most patients, reduced insight is
      the best predictor of non-adherence in patients who do not misuse alcohol or
      other drugs.

PMID- 16460919
TI  - Measuring microelastic properties of stratum corneum.
AB  - We explore the compression moduli of a thin biological tissue through probe
      microscopy. The elastic modulus (E') of isolated stratum corneum is measured at
      varying depths through the use of an atomic force microscope (AFM) as well as a
      nano-indentor (Hysitron Triboscope). In addition, a nano-DMA is used to measure
      visco-elastic properties. Measurements on dry and hydrated stratum corneum show
      an order of magnitude difference in E' and the measured tandelta (E''/E') is seen
      to increase from approximately 0.1 to 0.25. In addition, extensive validation of
      the experiments is conducted with different indentation probes at different force
      ranges to reveal the effects of indentor geometry and indentation depth on the
      measured elastic modulus. The sensitivity of the measurements is tested with
      applying known treatments to stratum corneum and exploring their effects on
      biomechanical parameters.

PMID- 16460920
TI  - The striatin family: a new signaling platform in dendritic spines.
AB  - Proteins of the striatin family have been identified in all multicellular
      animals. They are multidomain molecules containing several protein-interacting
      motifs. In mammals, these proteins are principally expressed in neurons with a
      somato-dendritic localization and high concentration in dendritic spines. Recent
      reports suggest that the proteins of the striatin family are molecular scaffolds
      that act as links between signal transduction and vesicular trafficking.

PMID- 16460921
TI  - Indoleamine 2,3-dioxygenase, tumor-induced tolerance and counter-regulation.
AB  - Tumors create an abnormal state of tolerance toward themselves and their
      antigens. One mechanism that might contribute to this tolerance is the
      immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO). IDO-expressing antigen
      presenting cells are found in tumor-draining lymph nodes, where they can create a
      tolerogenic microenvironment. IDO can also be expressed within the tumor itself,
      by tumor cells or host stromal cells, where it can inhibit the effector phase the
      immune response. Finally, emerging evidence suggests that IDO might also
      constitute a significant counter-regulatory mechanism, induced by clinically
      relevant pro-inflammatory signals, such as IFN-gamma, IFN-alpha, CpG
      oligodeoxynucleotides, and 4-1BB ligation. Strategies to inhibit the IDO pathway
      may thus assist in breaking tolerance to tumors, and might enhance the efficacy
      of other immunotherapy strategies by removing unwanted counter-regulation.

PMID- 16460922
TI  - Receptor editing for better or for worse.
AB  - Receptor editing has emerged from its original identification as a minor
      secondary mechanism of B cell tolerance to be considered as a dominant mechanism
      by which autoreactive immature B cells are rendered tolerant. Clonal deletion,
      previously regarded as the major mechanism of central B cell tolerance, has been
      shown by recent studies to operate secondarily and only when receptor editing is
      unable to provide a non-autoreactive specificity. Receptor editing has also been
      shown to operate during the development of wild-type B lymphocytes, and ongoing
      investigations demonstrate the influence of particular signaling molecules in the
      induction and/or inhibition of receptor editing. Together, these studies begin to
      map the signaling pathways that regulate receptor editing in autoreactive and non
      autoreactive immature B cells.

PMID- 16460923
TI  - A comparative study of capacitive immunosensors based on self-assembled
      monolayers formed from thiourea, thioctic acid, and 3-mercaptopropionic acid.
AB  - A procedure was developed for the covalent coupling of anti-alpha-fetoprotein
      antibody (anti-AFP) to a gold surface modified with a self-assembled monolayer
      (SAM) of thiourea (TU). The performance of the SAM-antibody layer was compared to
      those of similar layers based on thioctic acid (TA) and 3-mercaptopropionic acid
      (MPA) by using flow injection capacitive immunosensor system. Covalent coupling
      of anti-AFP on self-assembled thiourea monolayer (SATUM) modified gold electrode
      can be used to detect alpha-fetoprotein with high efficiency, similar
      sensitivity, the same linear range (0.01-10 microgl(-1)) and detection limit (10
      ngl(-1)) as those obtained from sensors based on self-assembled thioctic acid
      monolayer (SATAM) and self-assembled 3-mercaptopropionic acid monolayer (SAMPAM).
      The system is specific for alpha-fetoprotein and can be regenerated and reused up
      to 48 times. Therefore, self-assembled monolayer using thiourea which is cheaper
      than thioctic acid and 3-mercaptopropionic acid is a good alternative for
      biosensor applications when SAMs are used.

PMID- 16460925
TI  - Luminescent yeast cells entrapped in hydrogels for estrogenic endocrine
      disrupting chemical biodetection.
AB  - In the construction of luminescent yeast cell based fibre-optic biosensors, we
      demonstrate a novel approach for estrogenic endocrine disrupting chemical (EDC)
      biodetection by entrapping genetically modified Saccharomyces cerevisiae cells,
      containing the estrogen receptor alpha-mediated expression of the luc reporter
      gene, in hydrogel matrices based on calcium alginate or PVA. In order to insure a
      significant signal, an optimal immobilization ratio of 1:2 alginate 3% (w/v): 5 x
      10(6) [cells/ml], respectively, was used with the highest 17-beta-estradiol (beta
      E2) induction factor after 2.5 h of incubation with 10[nM] beta-E2. It was shown
      that biocompatible alginate beads, 4.27-4.55 x 10(5) [CFU/bead], which were
      characterized by a detection limit of 0.08[microg l(-1)] and an EC50 of
      0.64[microg l(-1)] for beta-E2, retained their viability for luminescence
      measurements after 1 month of storage at -80 degrees C slow freeze condition, and
      thus repeated cell cultivations were not required. The assay reproducibility for
      each tested EDC, represented by the coefficients of variation (CV), ranged from
      4.35 to 18.47%. An alternative immobilization method, based on a room temperature
      partial drying of polyvinyl alcohol (PVA) solution (LentiKat Liquid) and cell
      suspension mix, was investigated with only a slightly lower detection limit for
      beta-E2 than that reported with alginate beads. Alginate yeast based hydrogels
      may also be applicable to the analysis of environmental water samples since the
      trend of detected estrogenic activities with alginate beads roughly correlated
      with LC-MS-MS analytical results.

PMID- 16460924
TI  - Toxin detection based on action potential shape analysis using a realistic
      mathematical model of differentiated NG108-15 cells.
AB  - The NG108-15 neuroblastoma/glioma hybrid cell line has been frequently used for
      toxin detection, pharmaceutical screening and as a whole-cell biosensor. However,
      detailed analysis of its action potentials during toxin or drug administration
      has not been accomplished previously using patch clamp electrophysiology. In
      order to explore the possibility of identifying toxins based on their effect on
      the shape of intracellularly or extracellularly detected action potentials, we
      created a computer model of the action potential generation of this cell type. To
      generate the experimental data to validate the model, voltage dependent sodium,
      potassium and high-threshold calcium currents, as well as action potentials, were
      recorded from NG108-15 cells with conventional whole-cell patch-clamp methods.
      Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic
      description of the rate constants, ion-channel parameters were estimated using an
      automatic fitting method. Utilizing the established parameters, action potentials
      were generated in the model and were optimized to represent the actual recorded
      action potentials to establish baseline conditions. To demonstrate the
      applicability of the method for toxin detection and discrimination, the effect of
      tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a
      sodium channel opener) were studied. The two toxins affected the shape of the
      action potentials differently and their respective effects were identified based
      on the changes in the fitted parameters. Our results represent one of the first
      steps to establish a complex model of NG108-15 cells for quantitative toxin
      detection based on action potential shape analysis of the experimental results.

PMID- 16460926
TI  - Sweating the small stuff: microRNA discovery in plants.
AB  - The class of small RNAs known as microRNAs (miRNAs) has a demonstrated role in
      the negative regulation of gene expression in both plants and animals. These
      small molecules have been shown to play a critical role in a wide range of
      developmental and physiological pathways. Although hundreds of different miRNAs
      have now been identified using cloning and computational approaches,
      characterization of their targets and biological roles has been more limited. New
      sequencing technologies promise to accelerate the sequencing of small RNAs and
      additional genetic and genomic strategies are being applied to assess their
      regulatory function on RNA targets. These technologies will enable the
      identification of large numbers of small RNAs from diverse species, and
      comparative genomics approaches based on these data are likely to identify
      additional miRNAs. Combined with bioinformatics and experimental approaches to
      separate miRNAs from short-interfering RNAs (siRNAs), the pace of miRNA discovery
      is likely to accelerate, leading to an improved understanding of miRNA function
      and biological significance.

PMID- 16460927
TI  - "The Art of Successful Publication" ECCO 13 workshop report.
AB  - Having your work published in a good journal is the life-blood of research.
      Publications are the key element in scientific communication and influence future
      funding and cancer development for the authors. Every year more and more
      manuscripts are submitted and competition for acceptance is fierce. The editors
      of EJC recently held a workshop to discuss ways to improve manuscript writing,
      and this paper summarises their recommendations. Choose a title carefully, keep
      the introduction short, avoid confusing methods with results, and use figures
      wherever possible. Discuss only the relevance of new findings to published
      literature. Above all read the specific "instructions to authors" -- it is
      surprising how often this is ignored -- at peril!

PMID- 16460928
TI  - Cancer-related fatigue: A critical appraisal.
AB  - This aim of this systematic review was to determine the prevalence and pattern of
      cancer-related fatigue (CRF), and identify factors associated with its
      development. Relevant literature was identified through an electronic database
      search using specified keywords. Included studies investigated CRF in adult
      cancer patients using a multidimensional fatigue measure. The methodological
      quality was assessed using six published standards. CRF is apparent both during
      and after anti-cancer therapy, however, the prevalence of CRF varied between
      studies. The variables associated with the development and persistence of CRF
      remain to be identified. Inconsistencies were evident in the pattern of CRF and
      its associated factors. This is likely to have arisen from the inherent
      difficulties in the measurement of a subjective sensation, further complicated by
      the myriad of outcome measures used. More methodologically sound research;
      assessing CRF from the commencement of therapy, considering all pertinent
      variables is needed.

PMID- 16460929
TI  - A novel estrogen receptor-related protein gamma splice variant lacking a DNA
      binding domain exon modulates transcriptional activity of a moderate range of
      nuclear receptors.
AB  - A novel estrogen receptor-related protein (ERR) gamma splice variant cDNA
      (ERRgamma3) was found in human full-length cDNA libraries. ERRgamma3 cDNA
      consists of 3362 base pairs and has an open reading frame of 1188bp. The
      predicted peptide sequence of ERRgamma3 differs from both ERRgamma1 and ERRgamma2
      in missing 39 amino acid residues corresponding to the second zinc finger motif
      of the DNA binding domain (DBD). ERRgamma3 gene consists of 8 exons including
      three unique 5'-terminal exons and lacks the exon encoding the second zinc finger
      motif. The expression of ERRgamma3 was confined to adipocytes and prostate while
      that of ERRgamma2 was fairly widespread. The ERRgamma3 product was shown by
      transactivation assay to have no ability to activate ERE-controlled
      transcription. However, ERRgamma3 has an ability to modulate the transcriptional
      activity of other nuclear hormone receptors. ERRgamma3 augmented the ligand
      dependent transcriptional activities of ER (estrogen receptor) alpha, ERbeta, and
      thyroid receptor (TR) alpha by 1.3-, 4-, and 2.1-fold whereas it inhibited fully
      the activity of glucocorticoid receptor (GR). However, ERRgamma3 had no effect on
      Vitamin D3 receptor, retinoic acid receptor alpha or peroxisome proliferator
      activated receptor alpha, beta, and gamma. These findings will help to elucidate
      the physiological role of the ERRgamma subfamily.

PMID- 16460931
TI  - Synthesis of Pseudomonas quorum-sensing autoinducer analogs and structural
      entities required for induction of apoptosis in macrophages.
AB  - The synthesis of the analogs of N-3-oxododecanoyl-L-homoserine lactone (1) and
      their structure-activity relationship for the apoptotic induction in macrophages,
      P388D1 cells, are described. It was revealed that the position of the oxo group
      in the acyl side chain in addition to the presence of the L-homoserine lactone
      unit is crucial for the apoptosis-inducing activity. Furthermore, the long acyl
      side chains with hydrophobic distal ends are preferable for the activity.

PMID- 16460930
TI  - Synthesis of novel benzofuran isoxazolines as protein tyrosine phosphatase 1B
      inhibitors.
AB  - PTPases are considered to be involved in the etiology of diabetes mellitus and
      neural diseases, such as Alzheimer's disease and Parkinson's disease. Therefore,
      PTPase inhibitors should be useful tools to study the role of PTPases in these
      diseases and other biological phenomena, and which can be developed into
      chemotherapeutic agents. In the present study, we have synthesized novel
      benzofuran isoxazolines 13-21 via 1,3-dipolar cycloaddition reaction using
      karanjin (1) and kanjone (2), isolated from Pongamia pinnata fruits. All the
      synthesized compounds were evaluated against PTPase enzyme. Compounds 19 and 20
      displayed significant inhibitory activity with IC50 values 76 and 81 microM,
      respectively.

PMID- 16460932
TI  - Discovery of novel heterocyclic factor VIIa inhibitors.
AB  - Structure-activity relationships and binding mode of novel heterocyclic factor
      VIIa inhibitors will be described. In these inhibitors, a highly basic 5
      amidinoindole moiety has been successfully replaced with a less basic 5
      aminopyrrolo[3,2-b]pyridine scaffold.

PMID- 16460933
TI  - Structure-guided identification of novel VEGFR-2 kinase inhibitors via solution
      phase parallel synthesis.
AB  - Structural analysis of the essential binding elements of the oxindole-based
      kinase inhibitor (1) led to the identification of a novel class of heterocyclic
      substituted pyrazolones. Knoevenagel condensation of a variety of activated
      methylene nucleophiles with indole or pyrrole carboxaldehydes provided a focused
      library of molecules, each containing elements of kinase pharmacophore probe.
      Initial screening for VEGFR-2 kinase inhibition eliminated several of the probes.
      Identification of an active pyrazolone motif and further optimization resulted in
      several highly potent VEGFR-2 inhibitors with cellular efficacy, anti-angiogenic
      activity ex vivo in rat aortic ring explant cultures, and oral anti-tumor
      efficacy in nude mice.

PMID- 16460934
TI  - Cytotoxic activities of water-soluble chitosan derivatives with different degree
      of deacetylation.
AB  - Chitosans with different degree of deacetylation (DD) (90% and 50% deacetylated
      chitosan) were prepared by N-deacetylation followed by grafted onto chitosan to
      form water-soluble aminoethyl-chitosan (AE-chitosan), and dimetylaminoethyl
      chitosan (DMAE-chitosan), diethylaminoethyl-chitosan (DEAE-chitosan). In the
      present study, cytotoxic activities of the chitosan derivatives were evaluated
      using three tumor cell lines and two normal cell lines, and structure-activity
      relationship was suggested. The cytotoxic activity was dependent on their DD and
      substituted group.

PMID- 16460935
TI  - A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the
      complement component C1s.
AB  - Inhibiting the classical pathway of complement activation by attenuating the
      proteolytic activity of the serine protease C1s is a potential strategy for the
      therapeutic intervention in disease states such as hereditary angioedema,
      ischemia-reperfusion injury, and acute transplant rejection. A series of
      arylsulfonylthiophene-2-carboxamidine inhibitors of C1s were synthesized and
      evaluated for C1s inhibitory activity. The most potent compound had a Ki of 10nM
      and >1000-fold selectivity over uPA, tPA, FX(a), thrombin, and plasmin.

PMID- 16460936
TI  - Inhibitors of VEGF receptors-1 and -2 based on the 2-((pyridin-4
      yl)ethyl)pyridine template.
AB  - We have developed a series of novel potent ((pyridin-4-yl)ethyl)pyridine
      derivatives active against kinases VEGFR-1 and -2. Both specific and dual ATP
      competitive inhibitors of VEGFR-2 were identified. Kinase selectivity could be
      controlled by varying the arylamino substituent at the 1,3,4-oxadiazole ring. The
      most specific molecules displayed >10-fold selectivity for VEGFR-2 over VEGFR-1.
      Compound activities in vitro and in cell-based assays (IC(50)<100nM) were similar
      to those of reported clinical and development candidates, including PTK787
      (Vatalanibtrade mark). High permeability of active compounds across the Caco-2
      cell monolayer (>30x10(-5)cm/min) is indicative of their potential for intestinal
      absorption upon oral administration.

PMID- 16460937
TI  - Synthesis and evaluation of novel heterocyclic inhibitors of GSK-3.
AB  - A set of novel heterocyclic pyrimidyl hydrazones has been synthesized as
      inhibitors of glycogen synthase kinase-3 (GSK-3) with the most active exhibiting
      low nanomolar activity. Quantum mechanical calculations indicate that of the
      conformational factors that could determine binding affinity, the planarity of
      the phenyl ring in relation to the central core and the conformation of the
      hydrazone chain may be the most influential.

PMID- 16460938
TI  - Synthesis and preliminary biological evaluation of the 99mTc labeled
      nitrobenzoimidazole and nitrotriazole as tumor hypoxia markers.
AB  - 1-(3-1,2,4-Nitrotriazole-1-yl)-propanhydroxyiminoamide and 1-(6
      nitrobenzoimidazole-1-yl)-propanhydroxyiminoamide were synthesized and
      radiolabeled with (99m)Tc. The (99m)Tc labeled complexes continuously accumulated
      in hypoxic murine sarcoma S180 cells in vitro but not in aerobic cells.
      Biodistribution results in mice bearing S180 tumor indicated that the tracers
      could localize in tumor and eliminate from it slowly. These results suggested
      that the (99m)Tc labeled nitrobenzoimidazole and nitrotriazole might be the novel
      tumor hypoxia markers.

PMID- 16460939
TI  - Orally active thrombin inhibitors. Part 2: optimization of the P2-moiety.
AB  - Synthesis and SAR of orally active thrombin inhibitors of the d-Phe-Pro-Arg type
      with focus on the P2-moiety are described. The unexpected increase in in vitro
      potency, oral bioavailability, and in vivo activity of inhibitors with
      dehydroproline as P2-isostere is discussed. Over a period of 24h the antithrombin
      activity of the most active inhibitors with IC(50)s in the nanomolar range was
      determined in dogs demonstrating high thrombin inhibitory activity in plasma and
      an appropriate duration of action after oral administration.

PMID- 16460940
TI  - Biological evaluation of a multi-targeted small molecule inhibitor of tumor
      induced angiogenesis.
AB  - RO4396686 is a small molecule KDR, FGFR, and PDGFR inhibitor with good
      pharmacokinetic properties in rodents. In a mouse corneal neovascularization
      assay, this compound inhibited VEGF-induced angiogenesis. Tested in a H460a
      xenograft tumor model this agent effected significant tumor growth inhibition at
      doses as low as 50mg/kg.

PMID- 16460941
TI  - Phage display in the study of infectious diseases.
AB  - Microbial infections are dependent on the panoply of interactions between
      pathogen and host and identifying the molecular basis of such interactions is
      necessary to understand and control infection. Phage display is a simple
      functional genomic methodology for screening and identifying protein-ligand
      interactions and is widely used in epitope mapping, antibody engineering and
      screening for receptor agonists or antagonists. Phage display is also used widely
      in various forms, including the use of fragment libraries of whole microbial
      genomes, to identify peptide-ligand and protein-ligand interactions that are of
      importance in infection. In particular, this technique has proved successful in
      identifying microbial adhesins that are vital for colonization.

PMID- 16460942
TI  - Animal movements and the spread of infectious diseases.
AB  - Domestic and wild animal population movements are important in the spread of
      disease. There are many recent examples of disease spread that have occurred as a
      result of intentional movements of livestock or wildlife. Understanding the
      volume of these movements and the risks associated with them is fundamental in
      elucidating the epidemiology of these diseases, some of which might entail
      zoonotic risks. The importance of the worldwide animal trade is reviewed and the
      role of the unregulated trade in animals is highlighted. A range of key examples
      are discussed in which animal movements have resulted in the introduction of
      pathogens to previously disease-free areas. Measures based on heightened
      surveillance are proposed that mitigate the risks of new pathogen introductions.

PMID- 16460943
TI  - Correlation weighting of valence shells in QSAR analysis of toxicity.
AB  - In the rainbow trout (Oncorhynchus mykiss), we studied the acute toxicity LC(50)
      96 h of 274 organic pesticides with a wide variety of molecular structures.
      Optimization of correlation weights of local and global graph invariants (OCWLGI)
      gave quantitative structure-activity relationships (QSARs) for predicting
      toxicity. We used a labeled hydrogen-filled graph (LHFG) to elucidate the
      molecular structure. We also used the extended connectivity of zero ((0)EC(k)),
      first ((1)EC(k)), and second ((2)EC(k)) order, numbers of path lengths 2 (P2(k))
      and 3 (P3(k)) starting from a given vertex in the LHFG, and valence shells of
      second order (S2(k)). S2(k) is the sum of the degree of vertices at distance 2
      from a given vertex k. The presence of three-, five-, and six-member cycles and
      hydrogen bond indices suggested they might be used as global LHFG invariants. We
      applied this method to a broad set of pesticides, to predict toxicity for the
      trout. The best model used weighted S2(k) and global LHFG invariants. Statistical
      characteristics of this model are as follows: n=233, r(2)=0.7689,
      r(2)(pred)=0.7688, s=0.75, F=769 (training set); n=41, r(2)=0.6421,
      r(2)(pred)=0.4241, s=1.14, F=70 (test set).

PMID- 16460946
TI  - Synthesis and biological evaluation of new dipyrrolo[3,4-a:3,4-c]carbazole
      1,3,4,6-tetraones, substituted with various saturated and unsaturated side chains
      via palladium catalyzed cross-coupling reactions.
AB  - The syntheses of a series of dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones,
      substituted in 10-position with saturated and unsaturated side chains, via
      palladium catalyzed cross-coupling reactions, are described. These compounds can
      be considered as granulatimide bis-imide analogues. Their inhibitory activity
      toward Chk1 kinase and their antiproliferative activities in vitro in four tumor
      cell lines are reported.

PMID- 16460944
TI  - A new type of ketolide bearing an N-aryl-alkyl acetamide moiety at the C-9
      iminoether: synthesis and structure-activity relationships.
AB  - A new type of ketolide bearing an N-aryl-alkyl acetamide moiety at the C-9
      iminoether and its analogues were prepared, and their antibacterial activities
      and pharmacokinetic properties were evaluated. We found that the introduction of
      an (R)-alkyl group between the amide and iminoether groups could improve the
      pharmacokinetic properties while maintaining the activity against erythromycin
      resistant Streptococcus pneumoniae. Among the ketolides prepared with the (R)
      alkyl group, compound 5p with an N-(3-quinoxalin-6-yl-propyl)-propionamide moiety
      was found to have in vivo efficacy comparable to CAM with potent in vitro
      antibacterial activities against the key respiratory pathogens including
      Haemophilus influenzae and erythromycin-resistant S. pneumoniae.

PMID- 16460945
TI  - Novel bis(1-acyl-2-pyrazolines) of potential anti-inflammatory and molluscicidal
      properties.
AB  - A variety of bis[3-aryl-4,5-dihydro-1H-pyrazol-1-carboxaldehydes] 4a-h were
      obtained via reaction of bis[1-aryl-2-propen-1-ones] 3a-h with hydrazine hydrate
      in refluxing formic acid. In addition, the corresponding bis[1-acetyl-3-aryl-4,5
      dihydro-1H-pyrazoles] 4i-m were formed through conducting the reaction of 3 with
      hydrazine hydrate in refluxing acetic acid. The starting bis(2-propen-1-ones) 3a
      h were prepared stereoselectively as E,E'-geometric isomer via condensation of
      bisbenzaldehydes 1a,b with (un)substituted acetophenones 2 in ethanolic KOH
      solution. Anti-inflammatory as well as ulcerogenic activities of the prepared
      pyrazolines were evaluated in vivo and compared with that of a standard drug
      (indomethacin). Many of the tested compounds show remarkable anti-inflammatory
      properties with an ulcerogenic liability (especially 4f, g, j, and k) lower than
      that of the standard used drug. Compound 4f was established to be the best
      effectively prepared anti-inflammatory active pyrazoline derivative and safer
      than indomethacin with respect to its ulcerogenic liability. Molluscicidal
      activity of the prepared compounds against Biomphalaria alexandrina snails (the
      intermediate host of Schistosoma mansoni) was screened. Where, some of the
      prepared compounds show considerable activities.

PMID- 16460947
TI  - Comparative structure-activity relationships of benztropine analogues at the
      dopamine transporter and histamine H(1) receptors.
AB  - Benztropine (BZT) and its analogues inhibit dopamine uptake and bind with
      moderate to high affinity to the dopamine transporter (DAT). However, many of
      these compounds, in contrast to other monoamine uptake inhibitors, lack cocaine
      like behavioral effects and fail to potentiate the effects of cocaine. The BZT
      analogues also exhibit varied binding affinities for muscarinic M(1) and
      histamine H(1) receptors. In this study, a comparative analysis was conducted of
      pharmacophoric features with respect to the activities of BZT analogues at the
      DAT and at the histamine H(1) receptor. The BZT analogues showed a wide range of
      histamine H(1) receptor (K(i)=16-37,600 nM) and DAT (K(i)=8.5-6370 nM) binding
      affinities. A stereoselective histamine H(1)-antagonist pharmacophore, using a
      five-point superimposition of classical antagonists on the template,
      cyproheptadine, was developed. A series of superimpositions and comparisons were
      performed with various analogues of BZT. In general, smaller substituents were
      well tolerated on the aromatic rings of the diphenyl methoxy group for both the
      DAT and H(1) receptor, however, for the H(1) receptor, substitution at only one
      of the aromatic rings was preferred. The substituents at the 2- and N-positions
      of the tropane ring were preferred for DAT, however, these groups seem to overlap
      receptor essential regions in the histamine H(1) receptor. Molecular models at
      the DAT and the histamine H(1) receptor provide further insight into the
      structural requirements for binding affinity and selectivity that can be
      implemented in future drug design.

PMID- 16460949
TI  - Synthesis of substrate analogs of methyltransferases in the vitamin B(12)
      biosynthetic pathway and characterization of their enzymatic products.
AB  - The specificity toward substrate analogs of the first two methyltransferases in
      the vitamin B(12) biosynthetic pathway was probed with 15 synthetic
      porphyrinogens. Several novel methylated chlorins and isobacteriochlorins were
      isolated and characterized, suggesting the same methylation sequence C-2>C-7>C-20
      as for the natural substrate, uro'gen III. The results allow us to narrow down
      possible structural requirements concerning substrate recognition by the
      methyltransferase enzymes.

PMID- 16460948
TI  - [(S)-gamma-(Arylamino)prolyl]thiazolidine compounds as a novel series of potent
      and stable DPP-IV inhibitors.
AB  - Dipeptidyl peptidase-IV (DPP-IV) inhibitors, or glucagon-like peptide-1 (GLP-1)
      enhancers, are looked to as a potential new class of antidiabetic agents. In
      particular, potent and long-acting inhibitors might offer advantages in
      exploiting DPP-IV inhibition. The series of [(S)-gamma-(arylamino)prolyl]-(S)-2
      cyanopyrrolidine compounds on which we reported previously has a highly potent
      inhibitory activity but seemed to be unstable in neutral aqueous solution. Here,
      we describe [(S)-gamma-(arylamino)prolyl]thiazolidine compounds as a novel series
      of potent and stable DPP-IV inhibitors. They are the thiazolidine analogs of [(S)
      gamma-(arylamino)prolyl]-(S)-2-cyanopyrrolidine but with the electrophilic
      nitrile removed to improve chemical stability in aqueous solution. Of the
      compounds investigated in the present study, the [((S)-gamma-3,4
      dicyanophenylamino)prolyl]thiazolidine 12 m was the most potent. The structure
      activity relationship (SAR) of the gamma-substituent in the proline moiety of the
      thiazolidide was similar to that obtained with the (S)-2-cyanopyrrolidide. The
      gamma-substituent in the proline moiety of both the (S)-2-cyanopyrrolidide and
      the thiazolidide may engage with the S(2) binding pocket of DPP-IV and thereby
      achieve hydrophobic interaction in the same manner. Based on pharmacokinetic
      experiments in rats, the representative compound 11, which displayed high oral
      bioavailability (BA=83.9%) and long half-life in plasma (t(1/2)=5.27 h), was
      found to have an excellent pharmacokinetic profile.

PMID- 16460950
TI  - Synthesis and anticonvulsant activity of a class of 2-amino 3-hydroxypropanamide
      and 2-aminoacetamide derivatives.
AB  - Several studies have demonstrated that N-substituted amino acid derivatives
      exhibit weak anticonvulsant activities in vivo. In the present study, a series of
      amides of aminoacids structurally related to aminoacetamide have been synthesised
      and investigated for anticonvulsant activity. Among the molecules investigated,
      those containing a bicyclic (tetralinyl, indanyl) group linked to the
      aminoacetamide chain (40, 47 and 59) were among the most active as
      anticonvulsants (ED50 > 10, <100 mg/kg after oral administration) against tonic
      seizures in the mouse maximal electroshock, bicuculline and picrotoxin tests at
      doses devoid of neurotoxic activity. Altogether, these results suggest the
      described compounds as a class of orally available anticonvulsants. The ability
      of these compounds to partially block veratridine-induced aspartate efflux from
      rat cortical synaptosomes suggests that their anticonvulsant activity may be only
      partly the consequence of an interaction with neuronal voltage-dependent sodium
      channels. Some of the most potent compounds appear worthy of a further
      investigation aimed at assessing their anticonvulsant activity in other models
      and at elucidating the underlying mechanism of action.

PMID- 16460951
TI  - Study on the compounds containing 19F and 10B atoms in a single molecule for the
      application to MRI and BNCT.
AB  - Magnetic resonance imaging (MRI) and boron-neutron capture therapy (BNCT) are
      quite attractive techniques for diagnosis and treatment of cancer, respectively.
      In order to progress the study on both MRI and BNCT, the novel compounds
      containing 19F and 10B atoms in a single molecule were designed and synthesized.
      In the present paper, the syntheses and the internalization rates into tumor
      cells of these compounds are elucidated.

PMID- 16460952
TI  - Synthesis and biological evaluation of (2S)- and (2R)-2-(3'
      phosphonobicyclo[1.1.1]pentyl)glycines as novel group III selective metabotropic
      glutamate receptor ligands.
AB  - The synthesis of (2S)- and (2R)-2-(3'-phosphonobicyclo[1.1.1]pentyl)glycine
      isomers (10 and 11), characterized by the bioisosteric replacement of the distal
      carboxylic group of 2-(3'-carboxybicyclo[1.1.1]pent-1-yl)glycine by the
      phosphonate moiety, was accomplished by a stereoselective Ugi condensation. The
      two isomers were tested for their activity against an array of metabotropic
      glutamate receptors, and the S-isomer (10) turned out to be a moderately potent
      and selective mGluR4 agonist.

PMID- 16460953
TI  - Mining the NCI antiviral compounds for HIV-1 integrase inhibitors.
AB  - HIV-1 integrase (IN) is an essential enzyme for effective viral replication and
      is a validated target for the development of antiretroviral drugs. Currently,
      there are no approved drugs targeting this enzyme. In this study, we have
      identified 11 structurally diverse small-molecule inhibitors of IN. These
      compounds have been selected by mining the moderately active antiviral molecules
      from a collection of 90,000 compounds screened by the National Cancer Institute
      (NCI) Antiviral Program. These compounds, which were screened at the NCI during
      the past 20 years, resulted in approximately 4000 compounds labeled as
      'moderately active.' In our study, chalcone 11 shows the most potent activity
      with an IC(50) of 2+/-1 microM against purified IN in the presence of both Mn(2+)
      and Mg(2+) as cofactors. Docking simulations using the 11 identified inhibitors
      as a training set have elucidated two unique binding areas within the active
      site: the first encompasses the conserved D64-D116-E152 motif, while the other
      involves the flexible loop region formed by amino acid residues 140-149. The
      tested inhibitors exhibit favorable interactions with important amino acid
      residues through van der Waals and H-bonding contacts.

PMID- 16460954
TI  - The detection of landmines by neutron backscattering: exploring the limits of the
      technique.
AB  - Neutron backscattering (NB) sensors have been proposed for Humanitarian De-mining
      applications. Recently, a prototype hand-held system integrating a NB sensor in a
      metal detector has been developed within the EU-funded DIAMINE Project. The
      results obtained in terms of performance of the NB systems and limitations in its
      use are presented in this work. It is found that the performance of NB sensors is
      strongly limited by the presence of the soil moisture and by its small-scale
      variations. The use of the neutron hit distribution to reduce false alarms is
      explored.

PMID- 16460955
TI  - Age-dependent DNA repair and cell cycle distribution of human skin fibroblasts in
      response to UVA irradiation.
AB  - Ageing process in cells is associated with oxidative stress. Ultraviolet A
      produces reactive oxygen species responsible for accumulation of DNA and cellular
      damage. After the evaluation of antioxidant enzyme activities and oxidative
      stress markers at the basal state, we have studied the responses to UVA stress of
      coetaneous fibroblasts, isolated from different male donors (2-88 years, n=23) in
      terms of cytotoxicity, genotoxicity and DNA repair capacities. For this purpose,
      we have determined level of DNA damage using the comet assay (single strand
      breaks and alkali-labile sites) and the cell cycle distribution after a 5 J/cm2
      irradiation. No differences with age were observed for antioxidant enzyme
      activities and oxidative stress markers. DNA strand breaks after UVA irradiation
      (5-20 J/cm2), was found to be age-dependent. DNA repair was slow and also
      significantly affected by ageing. The cell cycle distribution analysis showed
      that high repair correlated with high proliferative capacities at basal level.
      Twenty-four hours after the stress, fraction of young fibroblasts blocked in G1
      phase was significantly increased whereas significant modifications concerned the
      G2-M phase for adult and older fibroblasts. These results indicate an age
      dependent decline in the DNA repair capacities correlated with modifications of
      the cell cycle parameters.

PMID- 16460956
TI  - Human ovarian theca cells in culture.
AB  - Elucidating the regulation of androgen biosynthesis in ovarian theca cells is not
      only important for determining the mechanisms of regulation of estrogen
      biosynthesis throughout the menstrual cycle, but is also essential for
      understanding the pathogenesis of excess androgen biosynthesis and polycystic
      ovary syndrome (PCOS). Human theca cells in primary and long-term culture have
      provided model systems for examining theca cell differentiation as well as the
      mechanisms underlying basal and cAMP-regulated steroid biosynthesis at both the
      transcriptional and post-transcriptional level in normal and PCOS ovaries.
      Results of these studies are expected to lead to the identification of novel
      targets for clinical treatment of infertility and PCOS.

PMID- 16460957
TI  - G-protein-coupled receptors and tyrosine kinases: crossroads in cell signaling
      and regulation.
AB  - G-protein-coupled receptors and protein tyrosine kinases represent two prominent
      pathways for cellular signaling. As our knowledge of cell signaling pathways
      mediated by the superfamily of G-protein-coupled receptors and the smaller family
      of receptor tyrosine kinases expands, so does our appreciation of how these two
      major signaling platforms share information and modulate each other, otherwise
      termed "cross-talk". Cross-talk between G-protein-coupled receptors and tyrosine
      kinases can occur at several levels, including the receptor-to-receptor level,
      and at crucial downstream points (e.g. phosphatidylinositol-3-kinase, Akt/protein
      kinase B and the mitogen-activated protein kinase cascade). Regulation of G
      protein-coupled receptors by non-receptor tyrosine kinases, such as Src family
      members, also operates in signaling. A broader understanding of how G-protein
      coupled receptors and tyrosine kinases cross-talk reveals new insights into
      signaling modalities in both health and disease.

PMID- 16460958
TI  - Interleukin-1: a key inflammatory mediator in psoriasis?
AB  - The pro-inflammatory cytokine interleukin-1 (IL-1) is constitutively expressed by
      keratinocytes in vivo and has been shown to be expressed in psoriatic lesional
      skin. To determine what role the IL-1 system might contribute to the inflammatory
      process in psoriasis, semi-quantitative RT-PCR and cRNA microarray studies were
      performed on biopsies excised from lesional and non-lesional skin. Whilst IL
      1alpha mRNA levels showed a reduction in lesional skin in a subset of patients,
      steady state IL-1beta mRNA was increased markedly. Neither of the two IL-1
      receptor transcripts nor total IL-1 receptor antagonist exhibited major changes
      within the lesion. Expression of the IL-1-induced chemokine IL-8 was only
      observed in lesional epidermis. Functional genomic experiments comparing
      transcriptome profiles derived from psoriatic lesional skin and IL-1 stimulated
      keratinocytes demonstrated a striking level of overlap. Taken together, these
      data suggest that IL-1 is likely to be an important mediator in the initiation
      and maintenance of psoriatic plaques and may represent an attractive therapeutic
      target.

PMID- 16460960
TI  - Somatosensory cortical plasticity in carpal tunnel syndrome--a cross-sectional
      fMRI evaluation.
AB  - Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median
      nerve characterized by paresthesias and pain in the first, second, and third
      digits. We hypothesize that aberrant afferent input in CTS will lead to cortical
      plasticity. Functional MRI (fMRI) and neurophysiological testing were performed
      on CTS patients and healthy adults. Median nerve innervated digit 2 (D2), and
      digit 3 (D3) and ulnar nerve innervated digit 5 (D5) were stimulated during fMRI.
      Surface-based and ROI-based analyses consistently demonstrated more extensive and
      stronger contralateral sensorimotor cortical representations of D2 and D3 for CTS
      patients as compared to healthy adults (P < 0.05). Differences were less profound
      for D5. Moreover, D3 fMRI activation in both the contralateral SI and motor
      cortex correlated positively with the D3 sensory conduction latency. Analysis of
      somatotopy suggested that contralateral SI representations for D2 and D3 were
      less separated for CTS patients (3.8 +/- 1.0 mm) than for healthy adults (7.5 +/-
      1.2 mm). Furthermore, the D3/D2 separation distance correlated negatively with D2
      sensory conduction latency-the greater the latency, the closer the D2/D3 cortical
      representations (r = -0.79, P < 0.05). Coupled with a greater extent of SI
      representation for these CTS affected digits, the closer cortical representations
      can be interpreted as a blurred somatotopic arrangement for CTS affected digits.
      These findings provide further evidence that CTS is not manifest in the periphery
      alone. Our results are consistent with Hebbian plasticity mechanisms, as our
      cohort of CTS patients had predominant paresthesias, which produce more
      temporally coherent afferent signaling from affected digits.

PMID- 16460959
TI  - Celosomy is associated with prenatal exposure to cyclooxygenase inhibitors.
AB  - Celosomy is a term used for a group of congenital anomalies characterized by
      opening of the somatic wall with evisceration. The most common types of celosomy
      are gastroschisis and omphalocele. They have been associated with maternal age,
      cigarette smoking, environmental pollution, as well as prenatal exposure to
      vasoconstrictors and recreational drugs. The aim of this study was to evaluate
      the effect of prenatal exposure to various selective and non-selective
      cyclooxygenase-2 (COX-2) inhibitors on the abdominal wall defects in rat. A
      retrospective statistical analysis was performed on the basis of data collected
      in our laboratory in the years 1997-2004, during different teratological studies
      with COX-inhibitors (aspirin, DFU, DuP-697, ibuprofen, paracetamol, piroxicam,
      propyphenazone, tolmetin). Out of 6744 live born fetuses celosomy was revealed
      only in four animals exposed to different non-selective COX inhibitors. A single
      case of gastroschisis was also found in a rat exposed to the selective COX-2
      inhibitor. The fetal body weight was significantly lower in COX-exposed group of
      fetuses when compared with untreated control. It was also significantly decreased
      in non-malformed fetuses prenatally exposed to COX inhibitors when compared with
      untreated control. The fetal body weight and length were lower in fetuses born
      with gastroschisis than with omphalocele. However, when animals with both
      anomalies were pooled in one group the mean fetal body weight was marginally
      lower (p = 0.0523) when compared with non-malformed group, while no statistically
      significant differences were found for fetal length. The pooled statistical
      analysis done for the concurrent and our own historic data showed that only
      aspirin statistically increased the risk of abdominal wall defects in rat
      fetuses. The expected ratio for aspirin is 56.41 per 10,000 offsprings (p <
      0.05), which is over 10-times higher than ratio for all non-selective COX
      inhibitors, including aspirin (6.01/10,000; p < 0.05). No differences were found
      for selective COX-2 inhibitors. It could be stressed that aspirin, unlike other
      non-selective and selective COX-2 inhibitors increases the risk of the abdominal
      wall defects, which are observed more often in growth-retarded fetuses.

PMID- 16460961
TI  - Neural correlates of counting of sequential sensory and motor events in the human
      brain.
AB  - Little is known about the ability to enumerate small numbers of successive
      stimuli and movements. It is possible that there exist neural substrates that are
      consistently recruited both to count sensory stimuli from different modalities
      and for counting movements executed by different effectors. Here, we identify a
      network of areas that was involved in enumerating small numbers of auditory,
      visual, and somatosensory stimuli, and in enumerating sequential movements of
      hands and feet, in the bilateral premotor cortex, presupplementary motor area,
      posterior temporal cortex, and thalamus. The most significant consistent
      activation across sensory and motor counting conditions was found in the lateral
      premotor cortex. Lateral premotor activation was not dependent on movement
      preparation, stimulus presentation timing, or number word verbalization. Movement
      counting, but not sensory counting, activated the anterior parietal cortex. This
      anterior parietal area may correspond to an area recruited for movement counting
      identified by recent single-neuron studies in monkeys. These results suggest that
      overlapping but not identical networks of areas are involved in counting
      sequences of sensory stimuli and sequences of movements in the human brain.

PMID- 16460962
TI  - Imaging the neocortex in epilepsy with double inversion recovery imaging.
AB  - The neocortices of 10 patients with partial seizures and acquired lesions, 14
      patients with malformations of cortical development (MCD) and 33 patients with
      partial seizures and normal conventional MRI were quantitatively evaluated using
      whole brain double inversion recovery imaging (DIR) and Statistical Parametric
      Mapping (SPM). Compared to a group of 30 control subjects, DIR and objective
      voxel-by-voxel statistical comparison identified regions of significantly
      abnormal DIR signal intensity (DSI) in 9 out of 10 patients with acquired
      nonprogressive cerebral lesions and partial seizures. In all 9 patients, the
      areas of abnormal DSI concurred with abnormalities identified on visual
      inspection of conventional MRI. In all 14 patients with MCD, SPM detected regions
      of significantly abnormal DSI; all of which corresponded to abnormalities
      identified on visual inspection of conventional MRI. In addition, in both groups,
      there were areas that were normal on conventional imaging, which demonstrated
      abnormal DSI. Voxel-by-voxel statistical analysis identified significantly
      abnormal DSI in 15 of the 33 patients with cryptogenic focal epilepsy. In 10 of
      these, the areas of abnormal DSI concurred with epileptic EEG abnormality and
      clinical seizure semiology. Group analysis of MRI-negative patients with
      electroclinical seizure onset localising to the left temporal and left and right
      frontal regions revealed significantly abnormal DSI within the white matter of
      each respective lobe. DIR analysed using SPM was sensitive in patients with MCDs
      and acquired cerebral damage. Significant abnormalities in DSI in individual and
      grouped MRI-negative patients suggest that occult epileptogenic cerebral lesions
      are associated with subtle structural abnormalities. DIR is, therefore, a useful
      quantitative MRI technique for characterising epileptic foci and may contribute
      to presurgical evaluation.

PMID- 16460963
TI  - The fusiform face area is tuned for curvilinear patterns with more high
      contrasted elements in the upper part.
AB  - The ability to identify conspecifics from the face is of primary interest for
      human social behavior. Newborns' visual preference for schematic face-like
      stimuli has been recently related to a sensitivity for visual patterns with a
      greater number of elements in the upper compared to the lower part. At the adult
      level, neuroimaging studies have identified a network of cortical areas devoted
      to the detection and identification of faces. However, whether and how low-level
      structural properties of face stimuli contribute to the preferential response to
      faces in these areas remain to be clarified. Using functional magnetic resonance
      imaging (fMRI), here we investigated whether the adults' face-sensitive cortical
      areas show a preference for top-heavy patterns, similarly to newborns'
      preference. Twelve participants were presented with head-shaped and square
      patterns with either more elements in the upper or the lower vertical part. In
      the right fusiform gyrus ('fusiform face area', FFA), an area showing a
      preference for faces over other visual object categories, there was a larger
      activation for curvilinear patterns with more high-contrast elements in the upper
      part, even though these patterns were not perceived as face stimuli. These
      findings provide direct evidence that the FFA is tuned for geometrical properties
      fitting best with the structure of faces, a computational mechanism that might
      drive the automatic detection of faces in the visual world.

PMID- 16460964
TI  - The time course of visual word recognition as revealed by linear regression
      analysis of ERP data.
AB  - EEG correlates of a range of psycholinguistic word properties were used to
      investigate the time course of access to psycholinguistic information during
      visual word recognition. Neurophysiological responses recorded in a visual
      lexical decision task were submitted to linear regression analysis. First, 10
      psycholinguistic features of each of 300 stimulus words were submitted to a
      principal component analysis, which yielded four orthogonal variables likely to
      reflect separable processes in visual word recognition: Word length, Letter n
      gram frequency, Lexical frequency and Semantic coherence of a word's
      morphological family. Since the lexical decision task required subjects to
      distinguish between words and pseudowords, the binary variable Lexicality was
      also investigated using a factorial design. Word-pseudoword differences in the
      event-related potential first appeared at 160 ms after word onset. However,
      regression analysis of EEG data documented a much earlier effect of both Word
      length and Letter n-gram frequency around 90 ms. Lexical frequency showed its
      earliest effect slightly later, at 110 ms, and Semantic coherence significantly
      correlated with neurophysiological measures around 160 ms, simultaneously with
      the lexicality effect. Source estimates indicated parieto-temporo-occipital
      generators for the factors Length, Letter n-gram frequency and Word frequency,
      but widespread activation with foci in left anterior temporal lobe and inferior
      frontal cortex related to Semantic coherence. At later stages (>200 ms), all
      variables exhibited simultaneous EEG correlates. These results indicate that
      information about surface form and meaning of a lexical item is first accessed at
      different times in different brain systems and then processed simultaneously,
      thus supporting cascaded interactive processing models.

PMID- 16460965
TI  - Preserved aspects of cortical foot control in paraplegia.
AB  - While several recent imaging studies confirm that motor foot areas can still be
      activated in complete and chronic paraplegia, it remains unclear whether their
      functionality is also maintained or declines after years of "non-use". Force
      control is one of the most important and best investigated functions within the
      motor cortex. It has been repeatedly reported that the motor cortex is more
      active when higher forces have to be applied. We thus addressed the question of
      preserved cortical functions by comparing motor force control patterns in the
      event-related potentials of 10 motor complete paraplegic subjects and 10 controls
      after attempted (paraplegic patients)/executed (healthy controls) ballistic foot
      movements with three different force levels. In addition to the peak amplitudes
      reflecting force levels, peak latencies were also investigated to elucidate
      timing as another functional aspect of motor control. No significant group
      difference was found for the peak latencies, indicating that the timing of motor
      cortical activation is preserved. Concerning amplitudes, we found preserved
      cortical modulation of higher forces but distorted low force modulation,
      especially early after injury. These findings thus suggest that important aspects
      of cortical control over paralyzed limbs are maintained despite years of "non
      use".

PMID- 16460966
TI  - The 'when' and 'where' of perceiving signals of threat versus non-threat.
AB  - We tested the proposal that signals of potential threat are given precedence over
      positive and neutral signals, reflected in earlier and more pronounced changes in
      neural activity. The temporal sequence ('when') and source localization ('where')
      of event-related potentials (ERPs) elicited by fearful and happy facial
      expressions, compared to neutral control expressions, were examined for 219
      healthy subjects. We scored ERPs over occipito-temporal sites (N80, 50-120 ms;
      P120, 80-180 ms; N170, 120-220 ms; P230, 180-290 ms; N250, 230-350 ms) and their
      polarity-reversed counterparts over medial sites (P80, 40-120 ms; N120, 80-150
      ms; VPP, 120-220 ms; N200, 150-280 ms; P300, 280-450 ms). In addition to scoring
      peak amplitude and latency, the anatomical sources of activity were determined
      using low resolution brain electromagnetic tomography (LORETA). Fearful faces
      were distinguished by persistent increases in positivity, associated with a
      dynamical shift from temporo-frontal (first 120 ms) to more distributed cortical
      sources (120-220 ms) and back (220-450 ms). By contrast, expressions of happiness
      produced a discrete enhancement of negativity, later in the time course (230-350
      ms) and localized to the fusiform region of the temporal cortex. In common, fear
      and happiness modulated the face-related N170, and produced generally greater
      right hemisphere activity. These findings support the proposal that fear signals
      are given precedence in the neural processing systems, such that processing of
      positive signals may be suppressed until vigilance for potential danger is
      completed. While fear may be processed via parallel pathways (one initiated prior
      to structural encoding), neural systems supporting positively valenced input may
      be more localized and rely on structural encoding.

PMID- 16460967
TI  - Transient blood pressure changes affect the functional magnetic resonance imaging
      detection of cerebral activation.
AB  - Functional magnetic resonance imaging (fMRI) provides an indirect measure of
      cerebral activation that could be altered by factors directly affecting cerebral
      blood flow independent of changes in neuronal activation. Presently, we
      investigate how changes in blood pressure (BP) affect the activation detected
      with fMRI. fMRI scans were acquired in 33 rats under control conditions and
      following transient BP increases (norepinephrine, IV) or decreases (arfonad, IV)
      with and without electrical stimulation of the forepaw. Voxels correlating to
      either the stimulation or the change in BP time courses were identified. During
      transient hypertension, irrespective of forepaw stimulation, BP increases (i.e.,
      >10 mm Hg) produced a transient increase in the blood oxygen level-dependent
      (BOLD) intensity resulting in a significant numbers of voxels correlating to the
      BP time courses (P < 0.05), and the number of these voxels increased as BP
      increased, becoming substantial at BP > 30 mm Hg. The activation patterns with BP
      increases and stimulation overlapped spatially resulting in an enhanced cerebral
      activation to simultaneous forepaw stimulation (P < 0.05). BP decreases (>10 mm
      Hg) produced corresponding decreases in BOLD intensity, causing significant
      numbers of voxels correlating to the BP decreases (P < 0.005), and these numbers
      increased as BP decreased (P < 0.001). The BP decreases and stimulation time
      courses and responses were distinct, and hypotension did not affect the detection
      of the activation response to forepaw stimulation. The results indicate that
      substantial hypertension accompanying a stimulation paradigm produces a BOLD
      response that enhances the cerebral activation detected, whereas hypotension does
      not affect the detection of neuronal activation but does produce responses that
      could be interpreted as a 'deactivation'.

PMID- 16460968
TI  - Bilingual brain organization: a functional magnetic resonance adaptation study.
AB  - We used functional magnetic resonance adaptation (fMRA) to examine whether intra
      voxel functional specificity may be present for first (L1)- and second (L2)
      language processing. We examined within- and across-language adaptation for
      spoken words in English-French bilinguals who had acquired their L2 after the age
      of 4 years. Subjects listened to words presented binaurally through earphones. In
      two control conditions (one for each language), six identical words were
      presented to obtain maximal adaptation. The remaining six conditions each
      consisted of five words that were identical followed by a sixth word that
      differed. There were thus a total of eight experimental conditions: no-change
      (sixth word identical to first five); a change in meaning (different final word
      in L1); a change in language (final item translated into L2); a change in meaning
      and language (different final word in L2). The same four conditions were
      presented in L2. The study also included a silent baseline. At the neural level,
      within- and across-language word changes resulted in release from adaptation.
      This was true for separate analyses of L1 and L2. We saw no evidence for greater
      recovery from adaptation in across-language relative to within-language
      conditions. While many brain regions were common to L1 and L2, we did observe
      differences in adaptation for forward translation (L1 to L2) as compared to
      backward translation (L2 to L1). The results support the idea that, at the
      lexical level, the neural substrates for L1 and L2 in bilinguals are shared, but
      with some populations of neurons within these shared regions showing language
      specific responses.

PMID- 16460969
TI  - A percutaneous swine model of myocardial infarction.
AB  - INTRODUCTION: The aim of this study was to develop a percutaneous, low risk, and
      reproducible technique of MI that simulates human disease. METHODS: MI was
      induced in 44 swine (32.8+/-7.2 kg) by percutaneous embolization coil deployment
      in the left anterior descending coronary artery. Hemodynamic measurements, left
      heart catheterization, and echocardiography were performed pre, post, and 30 days
      after MI. 3D NOGA viability mapping was performed at baseline and 30 days.
      Excised hearts were examined histologically. RESULTS: Pre-MI mortality was 6.8%
      and 24 h mortality was 13.6%. All pigs that survived 24 h after MI remained alive
      at 30 days. The mean left ventricular ejection fraction decreased from 58.4% to
      42.1% (p<0.001) at 30 days. The average thrombolysis in myocardial infarction
      score was 3, 0, and 1.5 at baseline, post-MI, and 30 days, respectively. At 30
      days, the end diastolic diameter, end diastolic volume, end systolic volume, and
      wall motion index increased from 3.76 to 3.89 cm, 32.5 to 50.0 ml, 14.9 to 27.0
      ml, and 1.01 to 1.38, respectively (all p<0.05), while the ejection fraction
      decreased from 56.5% to 49.4% (p<0.01). Additionally, at 30 days, statistically
      significant reductions in both unipolar and bipolar voltage in the mid and apical
      regions of the left ventricle were observed. Postmortem pathology showed a
      transmural scar in the apical anteroseptal regions with fibrosis in the MI
      region, which accounted for 14.8% and 14.2% of the total left and right
      ventricular myocardial area and volume, respectively. DISCUSSION: This model of
      MI is reliable, reproducible, has a pathophysiology similar to humans, and a
      lower mortality and ventricular fibrillation rates compared to other models. This
      model may be used to evaluate the effects of pharmacologics, gene therapy, and
      stem cell transplantation for the treatment of cardiovascular disease as well as
      studying mechanisms of cardiac remodeling.

PMID- 16460970
TI  - Falls risk is associated with pain and dysfunction but not radiographic
      osteoarthritis in older adults: Tasmanian Older Adult Cohort study.
AB  - OBJECTIVE: To describe the association between knee and hip radiographic
      osteoarthritis (ROA), a measure of knee pain, stiffness and functional ability
      and objectively measured physiological falls risk predictors. METHODS: Cross
      sectional, population-based study of 850 randomly selected men and women aged 50
      80 years (mean 62.5, SD 7.4). Falls risk (Z score) was determined objectively
      with the short form Physiological Profile Assessment (PPA). Two observers
      assessed knee and hip ROA using the Altman atlas. Pain, stiffness and functional
      ability were assessed using the Western Ontario McMasters Osteoarthritis index
      (WOMAC). RESULTS: Overall, the study population was at a mild risk of falling. In
      multivariable analysis, the WOMAC function and pain score were significantly
      associated with reaction time, balance, proprioception, knee extension strength,
      and edge contrast sensitivity. Stiffness was associated with knee extension
      strength and edge contrast sensitivity. Males had a dose response association
      between the global WOMAC score and falls risk (r=0.17, P<0.001). Those who
      reported a global WOMAC score of 50 and above had a higher risk of falling
      compared to those with a score below 50 (Z score: 0.53 vs 0.14, P<0.001). Hip
      joint space narrowing (JSN) was significantly associated with knee extension
      strength (r=-0.10, P=0.003), however, no other significant associations were
      observed between ROA and falls risk predictors. CONCLUSION: Self-reported
      functional ability and pain, and to a lesser extent, stiffness (but not knee and
      hip ROA), have a modest but independent association with physiological predictors
      of falls risk.

PMID- 16460971
TI  - Return to work following varicose vein surgery: influence of type of operation,
      employment and social status.
AB  - OBJECTIVES: To determine factors which influence the time taken to return to work
      in patients undergoing varicose vein surgery. DESIGN: Prospective collection of
      data from patients at outpatient interview. SETTING: The Department of Vascular
      and Endovascular Surgery at a teaching hospital in the UK. PARTICIPANTS: Two
      hundred and fifteen consecutive employed or self-employed patients attending the
      outpatient clinic for review following varicose vein surgery. METHODS: Data was
      collected from patients in the outpatient clinic approximately 6 weeks following
      varicose vein surgery. Type of procedure, gender, occupation status, category of
      occupation, the incidence of complications and the time taken to return to work
      (RTW) was recorded. Statistics were performed using Kruskal-Wallis H, Mann
      Whitney U and chi-squared analysis. RESULTS: Two hundred and fifteen patients
      were included, 77 (36%) men and 138 (64%) women. One hundred and ninety-two (89%)
      were employed and 23 (11%) self-employed. One hundred and fifty-three underwent
      primary saphenofemoral (SFJ) surgery, 10 bilateral procedures, 23 primary
      saphenopopliteal surgery (SPJ), 14 redo operations, five combined SFJ and SPJ,
      two mid thigh perforator ligation, six phlebectomies without groin or popliteal
      surgery and two bilateral surgery for recurrence. There was no relationship of
      gender or incidence of complications to RTW. There was a significant difference
      (p<0.0001) between employed (median RTW 4 weeks, interquartile range 2-5 weeks)
      and self-employed patients (median 2 weeks, interquartile range 1-4 weeks).
      Occupation category did show an overall significant difference (p<0.0001) on
      Kruskal-Wallis H-testing. Paired Mann-Whitney U-analysis showed that this
      difference was between occupation class I (median RTW 2 weeks, interquartile
      range 1-3 weeks) and IIIN (median 3.5 weeks, interquartile range 2-5 weeks), IIIM
      (median 5 weeks, interquartile range 2-5 weeks), IV (median 4 weeks,
      interquartile range 2-6 weeks) and V (median 4 weeks interquartile range 3-6
      weeks), and between class II (median 3 weeks, interquartile range 2-4 weeks) and
      classes IIIM, IV and V. CONCLUSIONS: Employed patients and those involved in
      intensive manual labour are less likely to return to work early. There is no
      effect of gender or incidence of complications. On the basis of this study we
      would recommend that patients could return to work within 3 weeks of varicose
      veins surgery.

PMID- 16460972
TI  - Vascular knowledge in medieval times was the turning point for the humanistic
      trend.
AB  - OBJECTIVE: Knowledge of the history of our surgical specialty may broaden our
      viewpoint for everyday practice. We illustrate the scientific progress made in
      medieval times relevant to the vascular system and blood circulation, progress
      made despite prevailing religious and philosophical dogma. METHODS: We located
      all articles concerning vascular knowledge and historical reviews in databases
      such as MEDLINE, EMBASE and the database of abstracts of reviews (DARE). We also
      explored the database of the register from the French National Library, the
      French Medical Inter-University (BIUM), the Italian National Library and the
      French and Italian Libraries in the Vatican. All data were collected and analysed
      in chronological order. RESULTS: Medieval vascular knowledge was inherited from
      Greek via Byzantine and Arabic writings, the first controversies against the
      recognized vascular schema emanating from an Arabian physician in the 13th
      century. Dissection was forbidden and clerical rules instilled a fear of blood.
      Major contributions to scientific progress in the vascular field in medieval
      times came from Ibn-al-Nafis and Harvey. CONCLUSION: Vascular specialists today
      may feel proud to recall that once religious dogma declined in early medieval
      times, vascular anatomic and physiological discoveries led the way to scientific
      progress.

PMID- 16460973
TI  - Sleep, rhythms and women's mood. Part I. Menstrual cycle, pregnancy and
      postpartum.
AB  - This review summarizes studies of sleep and other biological rhythms during the
      menstrual cycle, pregnancy and the postpartum period, focusing, where feasible,
      on studies in women who met DSM-IV (Diagnostic and Statistical Manual for Mental
      Disorders, 4th edition) criteria for a depressive disorder compared with healthy
      controls. The aim was to review supporting evidence for the hypothesis that
      disruption of the normal temporal relationship between sleep and other biological
      rhythms such as melatonin, core body temperature, cortisol, thyroid stimulating
      hormone (TSH) or prolactin occurring during times of reproductive hormonal change
      precipitates depressive disorders in predisposed women. Treatment strategies,
      designed to correct these altered phase (timing) or amplitude abnormalities,
      thereby improve mood. Although there may be some common features to premenstrual,
      pregnancy and postpartum depressive disorders (e.g. elevated prolactin levels), a
      specific profile of sleep and biological rhythms distinguishes healthy from
      depressed women during each reproductive epoch. Further work is needed to
      characterize more fully the particular abnormalities associated with each
      reproductive state to identify common versus distinctive features for each
      diagnostic group. This information could serve as the basis for developing more
      targeted treatment strategies.

PMID- 16460974
TI  - Localization of SP- and CGRP-immunopositive nerve fibers in the hip joint of
      patients with painful osteoarthritis and of patients with painless failed total
      hip arthroplasties.
AB  - Using immunohistochemical methods we determined the presence of SP- and CGRP
      immunopositive nerve fibers in the hip joint of patients with femoral neck
      fracture (controls, group 1), painful osteoarthritis (group 2), and painless
      failed total hip arthroplasties (group 3). Immunoreactive nerve fibers were found
      in the soft tissue of the fossa acetabuli as well as in the subintimal part of
      the synovial layer in the hip joint capsule of groups 1 and 2. In the capsule of
      controls the innervation density had a median of 5.7fibers/cm(2) for CGRP-ir and
      3.2fibers/cm(2) for SP-ir afferents. In the osteoarthritic group, the density
      significantly increased to a median of 15.6fibers/cm(2) for CGRP-ir and
      8.2fibers/cm(2) for SP-ir neurons (p=0.05). Patients with failed hip
      arthroplasties completely lacked these neuropeptide containing afferents.
      Innervation density in the fossa acetabuli of osteoarthritc patients showed a
      median of 14.1fibers/cm(2) for CGRP-ir and 5.9fibers/cm(2) for SP-ir afferents.
      From these data we assume that the hip joint capsule and the soft tissue of the
      fossa acetabuli are important triggers of nociception. This is supported by the
      fact, that patients with loosened total hip arthroplasties, where we failed to
      detect SP- and CGRP-immunoreactive fibers, did not feel pain. The upregulation of
      SP- and CGRP-positive neurons in response to arthritic stages suggests a
      mechanism involving neuropeptides in the maintenance of a painful degenerative
      joint disease and in mediating noxious stimuli from the periphery. Furthermore,
      these findings help to explain clinical observations, such as effectiveness of
      local therapy to control hip pain with intraarticular injection, synovectomy and
      denervation procedures.

PMID- 16460975
TI  - Measurement of diffusion in the presence of shear flow.
AB  - We demonstrate here a method whereby molecular diffusion coefficients may be
      measured in the presence of the deformational flow field of a rheo-NMR cell. The
      method, which uses a repetitive CPMG train of rf pulses interspersed with
      magnetic field gradient pulses, allows the anisotropic diffusion spectrum to be
      directly probed. We focus on the cylindrical Couette cell, for which the radial,
      tangential, and axial directions correspond to the hydrodynamic velocity
      gradient, velocity, and vorticity directions. While ideal Couette flow does not
      perturb the vorticity direction, it does perturb diffusion measurements for the
      velocity gradient direction, and to a lesser extent, the velocity direction. We
      show that with closely spaced gradient pulses operating in a flow-compensating
      mode, there exists a diffusion limit below which one cannot measure, that scales
      as T(2)gamma(4), where gamma is the shear rate and T the gradient pulse
      repetition period. For a typical rheo-NMR cell, and for the more challenging
      velocity gradient direction, diffusion rates above 10(-12) m(2) s(-1) can be
      accurately measured (to 1% error) at shear rates up to 3s(-1). We demonstrate the
      use of the method in measuring the diffusion spectrum of a lyotropic lamellar
      phase under shear.

PMID- 16460976
TI  - Heat production and lipid metabolism in broiler and layer chickens during
      embryonic development.
AB  - We compared heat production (HP) and lipid metabolism in broiler and layer
      chickens (Gallus gallus) during embryonic development. To investigate HP and
      respiratory quotient (RQ), oxygen (O2) consumption and carbon dioxide (CO2)
      production were measured using an open-circuit calorimeter system. HP
      consistently had a tendency (P = 0.06) to be lower in broilers than in layers
      during embryonic development, and HP gradually decreased with developmental stage
      in both strains. RQ values of both strains were approximately 0.7 at every
      embryonic stage investigated. These results suggest that chicken embryos mainly
      use lipid for energy, and the RQ was significantly lower in broilers than in
      layers during embryonic development. Consumption of the yolk sac as a lipid
      source was faster in broilers than in layers. Plasma D-3-hydroxybutyrate (D3HB)
      and glycerol concentrations, associated with fatty acid oxidation, were lower in
      broiler than layer embryos. These results demonstrate that HP and lipid
      metabolism are different between the strains during embryonic development, and
      may be one factor for the growth difference between broiler and layer embryos.

PMID- 16460977
TI  - Antioxidant enzyme activity in endemic Baikalean versus Palaearctic amphipods:
      tagma- and size-related changes.
AB  - The activities of key antioxidant enzymes in two endemic Baikalean amphipod
      species: Pallasea cancelloides (Gerstf), Eulimnogammarus verrucosus (Gerstf) and
      the widely distributed Palearctic species Gammarus lacustris (Sars) were studied.
      This work was done to prove or disprove the hypothesis that Baikalean endemics
      have specifics in antioxidants system different from Palearctic species. The
      activities of antioxidant enzymes peroxidase, catalase and glutathione-S
      transferase were measured in different sections (tagmata) of the amphipods'
      bodies as well as in different size groups. Well expressed tagma-related
      differences in peroxidase activity as well as smaller differences in catalase
      activity were shown in all studied species. There were no measured differences in
      glutathione-S-transferase activity among body sections. The existence of size
      related changes in some antioxidant enzymes and the difference in such changes
      between Baikalean and Palearctic amphipods were noted. A significant increase in
      peroxidase activity with the size was found in both Baikalean species while a
      significant decrease in peroxidase activity was observed in the Palearctic G.
      lacustris. In Baikalean P. cancelloides, a significant decrease of catalase
      activity with the increase in age of crustaceans was noted, while in E.
      verrucosus no such relationship was found. In the Palearctic G. lacustris, a
      significant increase in catalase activity with the increase in size was noted.
      All species are shown to have no size-related differences in glutathione-S
      transferase activity. The differences between species as well as between both
      different tagmata and size-classes within a particular species were estimated. It
      was assumed that the estimated differences in enzymes activity most likely depend
      on interspecific variation, rather than on conditional specifics in Lake Baikal.

PMID- 16460978
TI  - Cloning and characterization of vitellogenin cDNA from the common Japanese conger
      (Conger myriaster) and vitellogenin gene expression during ovarian development.
AB  - The major yolk protein precursor, vitellogenin (VTG) was detected in plasma from
      vitellogenic females and estradiol-17beta (E2)-treated immature females, but not
      in males and immature females by Western blotting in common Japanese conger
      Conger myriaster. Its molecular mass was approximately 180 kDa under denaturing
      and reducing conditions. The common Japanese conger VTG cDNA was cloned from the
      liver of vitellogenic female. It contains 5110 nucleotides including an open
      reading frame that encodes 1663 amino acids. The deduced amino acid sequence of
      the common Japanese conger VTG shares 80% identity with that of eel Anguilla
      japonica VTG-1, and 45-55%, 32-34% and 27-29% identity with the deduced amino
      acid sequences of other fish, amphibian and avian VTG with polyserine domain,
      respectively. In female common Japanese conger, VTG gene was highly expressed in
      the liver of this species similar with other oviparous vertebrates. The
      expression levels of VTG gene in the liver increased from the oil droplet stage
      to the tertiary yolk globule stage and were maintained until the migratory
      nucleus stage.

PMID- 16460980
TI  - Mycobacterial infection as a precursor to sarcoid-like, corticosteroid
      responsive, diffuse granulomatous disease.

PMID- 16460979
TI  - Lipid content and fatty acid distribution in tissues from Portuguese dogfish,
      leafscale gulper shark and black dogfish.
AB  - The lipid characterization in tissues from the three deep-sea sharks leafscale
      gulper shark (Centrophorus squamosus), Portuguese dogfish (Centroscymnus
      coelolepis) and black dogfish (Centrocyllium fabricii) captured at Hatton Bank in
      the North Atlantic were examined. The objective was to determine the lipid
      content and the fatty acid composition in different tissues. In addition, the
      fatty acid composition in tissues and species was compared. The tissues examined
      were pancreas, heart, kidney, stomach, spleen and liver. The lipid content was
      high in liver (40-50%) and ranged from 1% to 5% in the other tissues. The
      dominant fatty acids were C16:0, C18:1 (n-9), C18:1 (n-7) and C22:6 (n-3) in all
      tissues. All tissues had a high content of unsaturated fatty acids.

PMID- 16460981
TI  - Clinical indicators of Pneumocystis jiroveci pneumonia (PCP) in South African
      children infected with the human immunodeficiency virus.
AB  - BACKGROUND: Pneumocystis pneumonia (PCP) caused by Pneumocystis jiroveci is
      common in HIV-infected children, producing substantial morbidity and mortality.
      Initiation of timely, effective therapy depends on clinical identification of
      children with PCP. OBJECTIVE: To develop a clinical decision rule to diagnose PCP
      in HIV-infected children for use where diagnostic resources are limited. METHODS:
      Analysis of data collected during a prospective incidence study of the etiology,
      features, and outcome of HIV-infected children hospitalized with pneumonia.
      RESULTS: Four clinical variables were independently associated with a diagnosis
      of PCP in multivariate analysis: age < 6 months (OR 15.6; 95% CI 2.4-99.8; p =
      0.004), respiratory rate > 59 breaths/min (OR 8.1; 95% CI 1.5-53.2; p = 0.018),
      arterial percentage hemoglobin oxygen saturation (SaO2) < or = 92% (OR 5.1; 95%
      CI 1.0-26.1; p = 0.052) and absence of history of vomiting (OR 11.2; 95% CI 1.9
      68.0; p = 0.008). The sensitivity and specificity of diagnosing PCP with any two
      or more of these variables were 1.00 (95% CI 0.74-1.00) and 0.49 (95% CI 0.39
      0.59), respectively. Diagnosing PCP with three or more of the indicators had a
      decreased sensitivity of 0.75 (95% CI 0.43-0.95) and increased specificity of
      0.90 (95% CI 0.83-0.95). CONCLUSION: Empirical anti-pneumocystis therapy should
      be considered in HIV-infected infants presenting with tachypnea, hypoxia and
      absence of vomiting.

PMID- 16460982
TI  - Five years of nosocomial Gram-negative bacteremia in a general intensive care
      unit: epidemiology, antimicrobial susceptibility patterns, and outcomes.
AB  - OBJECTIVES: Nosocomial Gram-negative bacteremia in the critically ill is
      associated with significant morbidity and mortality. This study provides
      epidemiological and antimicrobial susceptibility data for nosocomial Gram
      negative bacteremia in a general intensive care unit (ICU) over a five-year
      period. METHODS: Positive blood cultures from January 1, 1999 to December 31,
      2003 were reviewed for microbial etiology and susceptibilities. Patient charts
      were reviewed to determine the source of infection and outcome. RESULTS: Forty
      five nosocomial Gram-negative bacteremias occurred in 44 patients. Infection
      rates of 6.9/1000 admissions and 11.3/10,000 patient days remained stable.
      Admitting diagnoses included respiratory failure, solid organ transplant, post
      surgery, and multi-trauma. Seven bacterial species were identified; Pseudomonas
      aeruginosa and Enterobacter spp were most common. Sources of bacteremia included
      pneumonia (48.9%), and central venous catheterization (22.2%). Antimicrobial
      susceptibilities were highest for imipenem, gentamicin, tobramycin, ceftazidime,
      and piperacillin-tazobactam. Ciprofloxacin susceptibility was inferior to
      imipenem, gentamicin, and tobramycin (p < 0.05). Mortality rates were 53.3% in
      the ICU, and 60% for overall hospitalization. Average length of ICU stay was 50.5
      days compared to 6.13 days for all-comers. CONCLUSIONS: Nosocomial Gram-negative
      bacteremia is associated with marked morbidity and mortality in critically ill
      patients. Significant resistance to ciprofloxacin was demonstrated. Empiric
      treatment regimens should be based on unit-specific data.

PMID- 16460983
TI  - 60-kDa heat shock protein of Chlamydia pneumoniae promotes a T helper type 1
      immune response through IL-12/IL-23 production in monocyte-derived dendritic
      cells.
AB  - Infection, in particular by Chlamydia pneumoniae (Cp), has been associated with
      atherosclerosis and coronary heart disease. Immune reactions to heat shock
      proteins (HSPs) have been advocated to link infection to atherosclerosis and its
      acute sequelae based on molecular mimicry with host HSPs. We have here evaluated
      the role played by recombinant Cp-HSP60 and Cp-HSP10 for their ability to induce
      maturation of human monocyte-derived dendritic cells (MDDC) and T cell
      polarization. Cp-HSP60, but not Cp-HSP10, induced a strong MDCC maturation, as
      assessed by the expression of co-stimulatory molecules and other markers.
      Secretion of regulatory cytokines and enhancement of antigen presenting ability
      of mature (m)MDDC toward a clear T helper (Th) 1 pattern were also induced by Cp
      HSP60. An analysis of the IL-12 cytokine family demonstrated that Cp-HSP60
      matured MDDC were able to express p35 and p40 mRNA subunits to form IL-12, and
      p19 and p40 subunits to form IL-23. Thus, preferential Th1 polarization of immune
      response induced by Cp-HSP60-matured MDDC appears to be due to the concomitant
      expression of IL-12 and IL-23. Our data suggest that Cp-HSP60-matured DC may
      contribute to T-cell mediated immunopathology of atherosclerosis via a chronic
      stimulation of Th1 immune responses.

PMID- 16460984
TI  - Preventing the binding of pathogens to the host by controlling sphingolipid
      metabolism.
AB  - The binding of many pathogens and toxins to human cells can be inhibited by (1)
      depleting host cells of their surface glycosphingolipids; (2) coating the binding
      sites on pathogens (adhesins) with glycosphingolipid-like substances (decoys);
      (3) coating the host's glycosphingolipids with substances that compete with the
      pathogen for binding. Details of using these methods are described.

PMID- 16460985
TI  - Sydenham's chorea is associated with decreased verbal fluency.
AB  - BACKGROUND: Sydenham's chorea (SC) is a disorder associated with rheumatic fever
      and related to Streptococcus-induced immune reaction cross-reactive with basal
      ganglia antigens. Obsessive-compulsive disorder and other behavioral
      abnormalities have been described in SC. There are scarce data of cognitive
      function in this condition. OBJECTIVE: To assess verbal fluency in patients with
      SC. PATIENTS AND METHODS: We have compared the semantic (SVF) and phonemic verbal
      fluency (PVF) of 20 subjects with SC and 40 controls matched by age, gender and
      years of school. RESULTS: The scores of the control group on the SVF and PVF
      tests were 26.3 +/- 5.7 and 18.0 +/- 6.4 whereas the SC patients scored 25.1 +/-
      6.9 and 12.5 +/- 8.2. PVF was significantly decreased in the SC group (p < 0.01).
      CONCLUSION: SC is associated with reduction of PVF. This finding may reflect
      disruption of the dorsolateral prefrontal-striatal circuit caused by the auto
      immune process characteristic of SC.

PMID- 16460986
TI  - Chronic stimulation of the subthalamic nucleus increases daily on-time without
      dyskinesia in advanced Parkinson's disease.
AB  - We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN
      DBS) in 20 patients with Parkinson's disease (PD) by means of clinical
      assessments and patient diaries 12 months after surgery. STN-DBS reduced the
      UPDRS part III off-medication score by 33%, and successively improved complete
      daily on-time without dyskinesia at 12 months significantly. In conclusion, our
      study demonstrates the efficacy of chronic STN-DBS on motor features in a
      selected population of advanced PD patients. In addition to clinical assessments,
      patients' diaries serve as an essential tool to evaluate the functional motor
      status after STN-DBS.

PMID- 16460987
TI  - Altered coordination patterns in parkinsonian patients during trunk-assisted
      prehension.
AB  - We examined whether coordination between movement components during trunk
      assisted prehension was compromised in PD patients in response to varying
      constraints (experiment 1: reach speed, object size, movement amplitude;
      experiment 2: movement sequence). In general, both PD patients and controls
      responded similarly to the changes in these three variables. PD patients,
      however, demonstrated less synchronized movements in terms of timing between
      onsets and offsets of aperture formation, endpoint motion and trunk motion. In
      addition, PD patients used a pattern different from that of controls in
      specifying the relative contribution of trunk and arm to the endpoint motion. A
      significant group difference was observed in that controls tended to synchronize
      the involved movement components together, whereas PD patients did not show such
      a trend. These data suggest that PD patients have intact parameterization
      capabilities, although they have a reduced capability to coordinate multiple
      neuromotor synergies as a single unit.

PMID- 16460988
TI  - Regulation of bone biology by prostaglandin endoperoxide H synthases (PGHS): a
      rose by any other name...
AB  - It is well established that prostaglandins are essential mediators of bone
      resorption and formation. In the early 1990s, it was discovered that enzymatic
      reactions producing prostaglandins were regulated by two cyclooxygenase enzymes,
      one producing prostaglandins constitutively in tissues like the stomach,
      prostaglandin endoperoxide H synthase-1 (PGHS-1 or COX-1), and another induced by
      mitogens or inflammatory mediators (PGHS-2 or COX-2). This neat distinction has
      not been maintained because both enzymes act in different cell systems to provide
      physiological signaling, constitutively or by induction under certain conditions.
      For example, the regulation patterns of PGHS-1 and PGHS-2 are distinct, but the
      evidence shows that PGHS-2 functions constitutively in the skeleton. PGHS-2 has
      quickly been established, therefore, as a key regulator of bone biology, capable
      of rapid and transient expression in bone cells, and mediating
      osteoclastogenesis, mechanotransduction, bone formation and fracture repair. The
      goal of this review is to summarize the current state of our knowledge of PGHS
      regulation of bone metabolism and to identify some of the key unresolved
      challenges and questions that require further study.

PMID- 16460990
TI  - Characterizing cognition in ADHD: beyond executive dysfunction.
AB  - The hypothesis that Attention-Deficit/Hyperactivity Disorder (ADHD) reflects a
      primary inhibitory executive function deficit has spurred a substantial
      literature. However, empirical findings and methodological issues challenge the
      etiologic primacy of inhibitory and executive deficits in ADHD. Based on
      accumulating evidence of increased intra-individual variability in ADHD, we
      reconsider executive dysfunction in light of distinctions between 'hot' and
      'cool' executive function measures. We propose an integrative model that
      incorporates new neuroanatomical findings and emphasizes the interactions between
      parallel processing pathways as potential loci for dysfunction. Such a
      reconceptualization provides a means to transcend the limits of current models of
      executive dysfunction in ADHD and suggests a plan for future research on
      cognition grounded in neurophysiological and developmental considerations.

PMID- 16460991
TI  - Imitation: is cognitive neuroscience neglecting apraxia?

PMID- 16460992
TI  - Cognition through the lifespan: mechanisms of change.
AB  - Cognitive abilities rise steeply from infancy to young adulthood and then are
      either maintained or decline to old age, depending on the specific ability. This
      pattern suggests corresponding continuities of mechanism and process, but it is
      striking that the fields of cognitive development and cognitive aging make little
      contact with each other's methods and theories. In this review we examine reasons
      for this cultural separation, and show how recent findings from both areas fit a
      framework couched in terms of cognitive representation and control. These two
      broad factors have very different lifespan trajectories; consideration of their
      relative growth and decline makes it clear that cognitive aging is not simply
      'development in reverse'. This framework is offered in light of recent interest
      in finding greater continuity throughout the lifespan and creating a more
      comprehensive explanation of cognitive function and cognitive change.

PMID- 16460993
TI  - What language says about the psychology of events.
AB  - Despite the variety of verb meanings, linguistic research on their syntax and
      semantics has shown that they can be categorized into a finite and surprisingly
      small number of event types. More recently, research in the psycholinguistics of
      language acquisition and processing has emphasized the relevance of event type.
      The wider implication of these findings is that the conceptual fluidity of verbal
      concepts is confined by the fundamental structures of mental grammar, shedding
      light on this important interface between cognition and syntactic organization.

PMID- 16460994
TI  - Repetition effects to sounds: evidence for predictive coding in the auditory
      system.

PMID- 16460996
TI  - Cyclosporin A and cholestasis: Its mechanism(s) and clinical relevancy.

PMID- 16460995
TI  - Doctor-patient relationship as motivation and outcome: examining uses of an
      Interactive Cancer Communication System.
AB  - OBJECTIVE: To examine how the pre-existing doctor-patient relationship predicts
      conceptually distinct service use within an Interactive Cancer Communication
      System (ICCS) for underserved women with breast cancer and in turn how service
      utilization influences the doctor-patient relationship. METHODS: Study sample
      included 231 recently diagnosed, lower income breast cancer patients.
      Participants were provided a free computer, Internet access and training in how
      to use an ICCS called the Comprehensive Health Enhancement Support System (CHESS)
      "Living with Breast Cancer" program. Survey data was collected at pre-test and 4
      months after using the system, and use data about how women used the system was
      also collected. RESULTS: The only statistically significant predictor of service
      use was that patients with a more negative appraisal about the doctor-patient
      relationship used the Ask an Expert service more frequently, and there were
      trends toward a more negative appraisal of the doctor-patient relationship being
      associated with higher use of Information and Interactive services. Conversely,
      there was a trend toward a more positive appraisal predicting higher use of the
      Discussion Group service. In terms of statistically significant effects, more
      frequent utilization of Information services was associated with a more positive
      appraisal of the doctor relationship. CONCLUSION: While a more negative
      perception of the doctor-patient relationships at pre-test was associated with
      higher use of most of the conceptually distinct services within this ICCS, use of
      the Information services was associated with having a more positive appraisal of
      the doctor-patient relationship at post-test suggesting that high-quality
      information on the Internet can serve to improve patients' satisfaction with
      their doctor.

PMID- 16460997
TI  - Comparison of the grade evaluated by "Liver damage" of Liver Cancer Study Group
      of Japan and Child-Pugh classification in patients with hepatocellular carcinoma.
AB  - BACKGROUND: The "Liver damage" classification proposed by the Liver Cancer Study
      Group of Japan and Child-Pugh classification are both useful classifications for
      hepatic function. However, the factors responsible for the difference between the
      two classifications have not been fully investigated. METHODS: The medical
      records of 594 admissions of 220 patients with hepatocellular carcinoma (HCC)
      were retrospectively analyzed for encephalopathy, ascites, serum bilirubin and
      albumin, plasma retention rate (%) at 15min after injection of 0.5mg/kg of
      indocyanine green (ICG R15), and prothrombin time. RESULTS: Of 594 admissions,
      ICG R15 was tested in 337 (56.7%). The Child-Pugh classification was evaluated in
      all 594 admissions, but the "Liver damage" could be evaluated in 510 (85.9%) due
      to the lack of ICG R15 results. Of the 594 admissions, 372 (62.6%), 162 (27.3%),
      and 60 (10.1%) were Child-Pugh grade A, B, and C, respectively. Of the 510
      admissions, 219 (42.9%), 202 (39.6%), and 89 (17.5%) were "Liver damage" grade A,
      B, and C, respectively. The grade of "Liver damage" was similar to that of Child
      Pugh classification in 369 (72.4%), under-evaluated in 138 (27.1%), and over
      evaluated in 3 (0.6%). The Child-Pugh classification was statistically a better
      classification for predicting outcome than "Liver damage", but the "Liver damage"
      had better stratification ability than Child-Pugh classification in patients with
      relatively good liver function. CONCLUSIONS: Although the "Liver damage" could
      not be evaluated in some cases due to the lack of ICG R15 results, this
      classification system is useful in the evaluation and prediction of outcome of
      patients with early-stage liver diseases.

PMID- 16460999
TI  - Practical experience of high throughput real time PCR in the routine diagnostic
      virology setting.
AB  - The advent of PCR has transformed the utility of the virus diagnostic laboratory.
      In comparison to traditional gel based PCR assays, real time PCR offers increased
      sensitivity and specificity in a rapid format. Over the past 4 years, we have
      introduced a number of qualitative and quantitative real time PCR assays into our
      routine testing service. During this period, we have gained substantial
      experience relating to the development and implementation of real-time assays.
      Furthermore, we have developed strategies that have allowed us to increase our
      sample throughput while maintaining or even reducing turn around times. The
      issues resulting from this experience (some of it bad) are discussed in detail
      with the aim of informing laboratories that are only just beginning to
      investigate the potential of this technology.

PMID- 16460998
TI  - Seasonal distribution and phylogenetic analysis of human metapneumovirus among
      children in Osaka City, Japan.
AB  - BACKGROUND: Human metapneumovirus (hMPV) is one of the etiological agents of
      respiratory tract infection (RTI). Because clinical symptoms of hMPV resemble
      those caused by respiratory syncytial virus (RSV), clinical diagnosis of hMPV
      infection is difficult. Moreover, hMPV isolation using cultured cells is
      generally difficult and not efficient compared with reverse transcription-PCR (RT
      PCR). OBJECTIVES: To assess infection and seasonal distribution of hMPV
      associated with RTI among children in Osaka City, Japan. STUDY DESIGN: To detect
      the hMPV gene, we extracted viral RNA from clinical specimens of patients with
      RTI and performed RT-PCR or nested-PCR for the fusion (F) gene. hMPV-specific
      amplicons were sequenced and subjected to phylogenetic analysis. RESULTS: From
      June 2004 to May 2005, we detected 29 (20.1%) hMPV strains among 144 clinical
      specimens. Fifteen strains were detected by RT-PCR and the remaining 14 by nested
      PCR. Prevalence was principally in winter and spring with incidence peaking in
      April. We also detected the hMPV RNA from a patient with encephalitis.
      Approximately 80% of the hMPV-positive patients were younger than 3 years. To
      analyze these isolates precisely, a phylogenetic analysis using F gene was
      performed and demonstrated that Osaka City isolates of hMPV consists of two major
      genetic lineages each comprising two sublineages. CONCLUSIONS: We found two major
      genetic lineages of hMPV in Osaka City, Japan. We also found that nested-PCR was
      an efficient method for detecting the hMPV gene in clinical specimens. Of the 28
      patients presenting with hMPV infection, 1 patient had associated encephalitis
      suggesting that hMPV infection might play a role in inducing encephalitis.

PMID- 16461000
TI  - Fully automated quantitation of hepatitis B virus (HBV) DNA in human plasma by
      the COBAS AmpliPrep/COBAS TaqMan system.
AB  - BACKGROUND: The measurement of HBV DNA levels has become the most direct and
      reliable method used for accurate diagnosis and prognosis of acute and chronic
      HBV infection []. Nucleic acid amplification testing (NAT detection) also reduces
      the pre-seroconversion window period. The method can be used to aid in the
      management of HBV infection, by the identification of individuals with high
      levels of viral replication who might benefit from antiviral therapy, monitoring
      patients on therapy, and identification of the development of resistance.
      OBJECTIVES: Evaluation of the novel COBAS AmpliPrep/COBAS TaqMan HBV Test, which
      combines automated extraction of DNA on the COBAS AmpliPrep Instrument (CAP),
      coupled with real-time PCR on the COBAS TaqMan Analyzer (CTM), thus greatly
      reducing hands-on time during sample preparation and amplification/detection. The
      assay fulfils the current requirements: a highly sensitive HBV DNA detection
      reagent which is calibrated to the International WHO Standard to reliably
      quantify HBV genotypes A-G in plasma with a very broad measuring range, thereby
      minimizing laborious repeat testing. STUDY DESIGN: The test was evaluated for
      sensitivity, dynamic range, precision, clinical and analytical specificity,
      genotype inclusivity, interfering substances, and correlation with other tests
      for the detection of HBV DNA (COBAS Amplicor HBV Monitor Test, COBAS TaqMan HBV
      Test for Use with the High Pure System and VERSANT HBV DNA 3.0 Assay). RESULTS
      AND CONCLUSION: A fully automated system for sample preparation, amplification
      and quantitation of HBV DNA was developed that demonstrates a nearly 7-log
      dynamic range up to 1.1E+08IU/mL, an assay sensitivity (95% hit-rate) of 4
      12IU/mL and an equivalent detection of genotypes A-G plus a prevalent pre-core
      mutant. The results obtained with the new test show a good correlation to titers
      obtained with other platforms.

PMID- 16461001
TI  - Regulation of Akt by arachidonic acid and phosphoinositide 3-kinase in
      angiotensin II-stimulated vascular smooth muscle cells.
AB  - Angiotensin (Ang) II stimulates cytosolic phospholipase A2(cPLA(2))-dependent
      release of arachidonic acid (ArAc) in vascular smooth muscle cells (VSMC). ArAc
      release and production of reactive oxygen species (ROS) lead to the activation of
      downstream kinases resulting in VSMC growth. To determine the role of Akt in this
      pathway, we used VSMC to link Ang II-induced ArAc release and ROS production to
      the activation of Akt and VSMC growth. We observed that Ang II, ArAc, or H(2)O(2)
      increased Akt activation. The Akt inhibitor SH6 blocked Ang II-, ArAc-, or
      H(2)O(2)-induced Akt activation, as did inhibition of phosphoinositide 3-kinase
      (PI(3)K). Inhibition of cPLA(2) blocked Ang II effects, while the ROS scavenger
      NaC decreased Ang II- and ArAc-induced Akt activation. Inhibition of Akt blocked
      the (3)H-thymidine incorporation induced by all three agonists. Thus, Ang II
      induced ArAc release and ROS production leads to the PI(3)K-dependant activation
      of Akt and VSMC growth.

PMID- 16461002
TI  - Independent component analysis identifies ictal bitemporal activity in
      intracranial recordings at the time of unilateral discharges.
AB  - OBJECTIVE: To apply independent component analysis (ICA) in intracranial
      recordings to analyze interactions during temporal lobe seizures. METHODS:
      Seizures from 20 patients with bitemporal implantation were classified as
      unilateral or bilateral and analyzed with ICA. During the period preceding
      bilateral activity, correlation coefficients were calculated between ICA
      components having ictal activity during the unilateral seizure phase (early ICA
      components) and every channel of the original EEG. ICA components were classified
      as unilateral if the correlation was >0.2 exclusively with channels in one
      hemisphere; and bilateral if both hemispheres were involved. RESULTS: One hundred
      twenty-three seizures were analyzed. Thirty-two percent of visually classified
      unilateral seizures and 64% of bilateral seizures (during the unilateral phase)
      had bilateral ICA components. The proportion of early ICA components that were
      bilateral and the proportion of channels contralateral to the visually identified
      seizure with correlation higher than 0.2 with at least one early ICA component
      were significantly lower in seizures that stayed unilateral than in seizures that
      later became bilateral by visual inspection (11 and 10%, respectively, in
      unilateral seizures; 33 and 28% in bilateral seizures; P=0.001). CONCLUSIONS: In
      patients with bitemporal epilepsy, approximately 20% of the components extracted
      using ICA have a bitemporal distribution even at the time when the seizures are
      apparently unilateral. The presence of early contralateral ictal activity is more
      frequent and extensive in seizures that later become evidently bilateral.
      SIGNIFICANCE: Minimal contralateral seizure activity is present even when the
      discharge appears unilateral and this is more frequent in seizures which later
      spread to the contralateral temporal lobe.

PMID- 16461003
TI  - A P300-based brain-computer interface: initial tests by ALS patients.
AB  - OBJECTIVE: The current study evaluates the effectiveness of a brain-computer
      interface (BCI) system that operates by detecting a P300 elicited by one of four
      randomly presented stimuli (i.e. YES, NO, PASS, END). METHODS: Two groups of
      participants were tested. The first group included three amyotrophic lateral
      sclerosis (ALS) patients that varied in degree of disability, but all retained
      the ability to communicate; the second group included three non-ALS controls.
      Each participant participated in ten experimental sessions during a period of
      approximately 6 weeks. During each run the participant's task was to attend to
      one stimulus and disregard the other three. Stimuli were presented auditorily,
      visually, or in both modes. RESULTS: Two of the 3 ALS patient's classification
      rates were equal to those achieved by the non-ALS participants. Waveform
      morphology varied as a function of the presentation mode, but not in a similar
      pattern for each participant. CONCLUSIONS: The event-related potentials elicited
      by the target stimuli could be discriminated from the non-target stimuli for the
      non-ALS and the ALS groups. Future studies will begin to examine online
      classification. SIGNIFICANCE: The results of offline classification suggest that
      a P300-based BCI can serve as a non-muscular communication device in both ALS,
      and non-ALS control groups.

PMID- 16461004
TI  - Sweat artifact and respiratory artifact occurring simultaneously in
      polysomnogram.

PMID- 16461005
TI  - GerES IV pilot study: assessment of the exposure of German children to
      organophosphorus and pyrethroid pesticides.
AB  - Organophosphorus pesticides and pyrethroids are widely used in German agriculture
      and residential settings. Their occurrence in human biological samples can be
      used as an indicator for the exposure of children to these compounds. Using
      multivariate evaluation the routes of exposure can be identified. In the pilot
      study of GerES IV, metabolites of pyrethroids and organophosporus pesticides were
      analysed in urine of children aged 2-17 years (n = 396 and 363). The 95th
      percentiles for the metabolites of the pyrethroids in urine were: cis-DCCA 0.74
      microg/l, trans-DCCA 1.7 microg/l, DBCA 0.52 microg/l, F-PBA < 0.1 microg/l, and
      3-PBA 2.4 microg/l. 3-PBA was detected in 90% of the samples. The 95th
      percentiles for the organophosphorus metabolites in urine were: DMP 118 microg/l,
      DEP 20 microg/l, DMTP 124 microg/l, DETP 11 microg/l, DMDTP 11 microg/l, DEDTP <
      1.0microg/l. DMTP was the metabolite most frequently detected in the samples
      (90%). Based on the metabolites analysed in urine the exposure to
      organophosphorus pesticides is mainly influenced by age, consumption of fresh
      fruits and fruit juice, living in an urban area, and season. A rough estimation
      revealed that the ADI values for organophosphorus pesticides might be exceeded.
      However, these results require further exploration. The exposure to pyrethroids
      is influenced by age, sampling location, consumption of boiled vegetables, and
      the use of biocides indoors at home. In addition, a significant correlation
      between permethrin in house dust and the metabolite concentrations in urine could
      be observed. Thus it seems likely that ingestion of house dust contributes to
      children's exposure.

PMID- 16461006
TI  - Decreased circulating macrophage migration inhibitory factor (MIF) protein and
      blood mononuclear cell MIF transcripts in children with Plasmodium falciparum
      malaria.
AB  - Plasmodium falciparum malaria remains one of the most frequently lethal diseases
      affecting children in sub-Saharan Africa, yet the immune mediators that regulate
      pathogenesis are only partially defined. Since macrophage migration inhibitory
      factor (MIF) is important for regulating innate immunity in bacterial and
      parasitic infections, circulating MIF and peripheral blood mononuclear cell
      (PBMC) MIF transcripts were investigated in children with acute falciparum
      malaria. Peripheral blood levels of MIF-regulatory cytokines and effector
      molecules, including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-12, IL-10, transforming growth factor (TGF)-beta1, bicyclo
      prostaglandin (PG) E2, and nitric oxide synthase activity were also determined.
      Circulating MIF and PBMC MIF mRNA were significantly lower in children with acute
      malaria relative to healthy, malaria-exposed children. Peripheral blood MIF
      levels showed no association with either parasitemia or hemoglobin
      concentrations. Circulating MIF was, however, significantly associated with IL-12
      and TGF-beta1. Multiple regression analyses revealed that IFN-gamma was the most
      significant predictor of peripheral blood MIF concentrations. These findings
      suggest that reduced MIF production may promote enhanced disease severity in
      children with falciparum malaria.

PMID- 16461007
TI  - Stable CNS gene delivery with Sleeping Beauty armed with a high-capacity HSV
      virion.

PMID- 16461008
TI  - Targeted therapy of DNA tumor virus-associated cancers using virus-activated
      transcription factors.
AB  - DNA tumor virus-mediated tumorigenic processes typically involve functional
      inactivation of cellular tumor suppressors pRB and p53 by viral oncoproteins,
      with concomitant activation of oncogenic transcription factors such as E2Fs. This
      feature could be exploited to design a treatment for corresponding malignancies.
      Here, we report a gene therapy strategy for DNA tumor virus-associated cancers
      using a synthetic, E2F-regulated gene expression system named pESM6. This system
      contains multimerized E2F-responsive elements in combination with the binding
      sites for ubiquitous transcription factors Sp1 and CTF/NF1. pESM6 could drive a
      high-level transgene expression comparable to that of the CMV IE promoter and
      exert constitutive activity in cells expressing DNA tumor viral oncogenes. In
      contrast, it was effectively repressed by pRB and thus only minimally active in
      nontransformed cells. Expression of cytosine deaminase from pESM6 resulted in a
      highly efficient and specific killing of HPV-transformed fibroblasts (C3) after
      treatment with the prodrug 5-fluorocytosine. Also, an effective tumor mass
      reduction was observed when the vector was injected directly into C3 tumors
      implanted in C57BL/6 mice. pESM6 showed a superior performance throughout these
      experiments compared to the previously known E2F-regulated gene vector. These
      results clearly demonstrate the potential usability of pESM6 for the gene therapy
      of DNA tumor virus-associated cancers.

PMID- 16461011
TI  - Tian ma, an ancient Chinese herb, offers new options for the treatment of
      epilepsy and other conditions.
AB  - Our purpose is to bring attention to the antiepileptic properties of the Chinese
      herb tian ma and its constituents, as well as to suggest the potential for the
      development of new antiepileptic drugs (AEDs) related to this herb. All available
      literature regarding the chemistry, pharmacology, animal data, and clinical use
      of tian ma and its constituents are reviewed, showing that tian ma, its
      constituents, and its symbiotic fungus Armillaria mellea have antiepileptic
      properties in in vitro and in vivo models. One clinical study reportedly
      demonstrated the AED effects of a component of tian ma, vanillin. Thus, tian ma,
      its constituent vanillin, and its symbiotic fungus armillaria hold promise as
      cost-effective and less toxic alternatives to standard AEDs. In addition, similar
      chemical compounds may be developed as AEDs.

PMID- 16461009
TI  - Evaluation of adenovirus vectors containing serotype 35 fibers for vaccination.
AB  - In contrast to commonly used serotype 5-based adenovirus (Ad) vectors, Ad's
      containing fibers derived from B-group serotype 35 (Ad5/35) efficiently transduce
      human DCs ex vivo and appear to target antigen-presenting cells after intravenous
      injection into baboons. Based on this, Ad5/35 vectors could be valuable tools for
      immunotherapy and vaccination. On the other hand, a number of studies indicate
      that signaling through the B-group Ad receptor, CD46, can cause tolerance or
      immunosuppression. Since mice do not express CD46 in a human-like pattern, we
      studied the in vivo properties of Ad5/35 in transgenic mice that express CD46 in
      a pattern and at a level similar to those of humans. Hypersensitivity assays and
      analyses of frequencies of regulatory T cells and T cell responses did not
      indicate that Ad5/35 injection exerts detrimental effects on the host's immune
      system. An Ad5/35 vector expressing a model antigen was able to trigger a strong
      T cell response against the test antigen after intramuscular injection. Overall,
      compared to Ad5 vectors, Ad5/35 vectors had a better safety profile, reflected by
      lower serum levels of proinflammatory cytokines.

PMID- 16461012
TI  - Wilson's disease and benign epilepsy of childhood with centrotemporal (rolandic)
      spikes.
AB  - Cases with a clinical and electroencephalographic phenotype of benign epilepsy of
      childhood with centrotemporal spikes (BECTS) in association with a proven organic
      brain lesion have rarely been reported. To our knowledge, we herein describe for
      the first time a patient with Wilson's disease who subsequently manifested BECTS.
      Our case bolsters the argument that in at least some cases, BECTS is associated
      with organic brain disease.

PMID- 16461013
TI  - Inhibitory effects of four carbamate insecticides on acetylcholinesterase of male
      and female Carassius auratus in vitro.
AB  - The inhibitory effects of four carbamate insecticides, methomyl, thiodicarb,
      carbofuran and carbosulfan, on acetylcholinesterase of male and female Carassius
      auratus were investigated in the laboratory. Kinetic constants, biomolecular rate
      constant (k(i)), carbamylation rate constant (k2) and decarbamylation rate
      constant (k3) were determined in vitro. The ratios of bimolecular rate constant
      (female/male) for AChE reacting with methomyl, thiodicarb, carbofuran and
      carbosulfan were 1.03, 2.44, 1.03 and 1.106, respectively. The k(i) of AChE for
      thiodicarb was significantly higher in female fish than in male fish (P<0.05).
      The ratios of carbamylation rate constant (female/male) for methomyl, thiodicarb,
      carbofuran and carbosulfan were 1.18, 4.29, 3.53, and 2.07, respectively. The k2
      values of AChE for the above four carbamates were significantly higher in females
      than in males. The ratios of the decarbamylation rate constant (female/male) for
      methomyl, thiodicarb, carbofuran and carbosulfan were 1.02, 1.39, 1.06, and 1.98,
      respectively. Only for carbosulfan, the decarbamylation rate of AChE was
      significantly higher in the female than in the male, indicating that AChE of
      females inhibited by carbosulfan recovered more quickly than that of males. The
      above results suggest that the female in the sensitivity of AChE to carbamates
      was different from the male fish.

PMID- 16461015
TI  - CCCP enhances catecholamine release from the perfused rat adrenal medulla.
AB  - The present study was designed to investigate the effect of carbonyl cyanide m
      chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, on secretion of
      catecholamines from the isolated perfused model of the rat adrenal gland and to
      establish the mechanism of its adrenomedullary secretion. The perfusion of CCCP
      (3x10(-5) M) into an adrenal vein of for 90 min caused a great increase in
      catecholamine secretion. Tachyphylaxis to catecholamine-releasing effect of CCCP
      was not observed by repeated perfusion of it. The net catecholamine-releasing
      effects of CCCP were depressed by pretreament with pirenzepine (a selective
      muscarinic M(1)-receptor antagonist), chlorisondamine (a selective neuronal
      nicotinic receptor antagonist), nicardipine (an L-type Ca2+-channel antagonist),
      TMB-8 (an intracellular Ca2+-antagonist), and the perfusion of EGTA plus Ca2+
      free medium, respectively. In the presence of CCCP (3x10(-5) M), catecholamine
      secretory responses induced by ACh (5.32x10(-3) M), high K+ (5.6x10(-2) M, a
      direct membrane depolarizer), DMPP (10(-4) M, (a selective neuronal nicotinic
      receptor agonist), and McN-A-343 (10(-4) M, (a selective muscarinic M1-receptor
      agonist) were significantly enhanced. CCCP also significantly enhanced the
      catecholamine secretory responses evoked by Bay-K-8644 (10(-5) M), L-type Ca2+
      channel activator, and cyclopiazonic acid (10(-5) M), an inhibitor of Ca2+
      ATPase. Furthermore, the perfusion of FCCP (3x10(-5) M), a similar mitochondrial
      uncoupler, into an adrenal vein of for 90 min also caused a great increase in
      catecholamine secretion in a similar pattern with CCCP. Taken together, the
      results demonstrate that CCCP causes the catecholamine secretion from the
      perfused rat adrenal medulla in a calcium-dependent fashion. It is thought that
      this catecholamine secretory enhancement of CCCP may be mediated by both
      cholinergic receptor stimulation and membrane depolarization, which are relevant
      to the cytoplasmic Ca2+ increase by stimulation of the Ca2+ influx as well as by
      the inhibition of Ca2+ uptake into the cytoplasmic Ca2+ stores (both endoplasmic
      reticulum and mitochondria in chromaffin cells). It also seems that
      protonophores, such as CCCP, suppress mitochondrial Ca2+ uptake and increase the
      stimulated secretion of catecholamine by the secretagogues. These results
      indicate that mitochondria modulate catecholamine secretion by regulating the
      Ca2+ mobilization for exocytosis.

PMID- 16461014
TI  - Is fluoroacetate-specific defluorinase a glutathione S-transferase?
AB  - Fluoroacetate-specific defluorinase (FSD) is a critical enzyme in the
      detoxication of fluoroacetate. This study investigated whether FSD can be classed
      as a glutathione S-transferase (GST) isoenzyme with a high specificity for
      fluoroacetate detoxication metabolism. The majority of FSD and GST activity,
      using 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-epoxy-3-(p-nitrophenoxy)propane
      (EPNP) as GST substrates, in rat liver was cytosolic. GSTT1 specific substrate,
      EPNP caused a slight non-competitive inhibition of FSD activity. CDNB, a general
      substrate of GST isoenzyme, was a more potent non-competitive inhibitor of FSD
      activity. The fluoroacetate defluorination activity by GST isoenzymes was
      determined in this study. The results showed that the GSTZ1C had the highest
      fluoroacetate defluorination activity of the various GST isoenzymes studied,
      while GSTA2 had a limited activity toward fluoroacetate. The human GSTZ1C
      recombinant protein then was purified from a human GSTZ1C cDNA clone. Our
      experiments showed that GSTZ1C catalysed fluoroacetate defluorination. GSTZ1
      shares many of the characteristics of FSD; however, it accounts only for 3% of
      the total cytosolic FSD activity. GSTZ1C based enzyme kinetic studies has low
      affinity for fluoroacetate. The evidence suggests that GSTZ1 may not be the major
      enzyme defluorinating fluoroacetate, but it does detoxify the fluoroacetate. To
      clarify the identity of enzymes responsible for fluoroacetate detoxication,
      further studies of the overall FSD activity are needed.

PMID- 16461016
TI  - Developmental expression of FoxJ1.2, FoxJ2, and FoxQ1 in Xenopus tropicalis.
AB  - Members of the Fox gene family exhibit remarkably restricted patterns of
      expression where they have interesting, required functions during development. We
      have analyzed the developmental expression patterns of three members of the Fox
      gene family, FoxJ1.2, FoxJ2, and FoxQ1, which have not been previously described
      in Xenopus. FoxJ1.2 is expressed in the otic vesicle during late neurula stages
      and is then also expressed in the presumptive nephrostomes of the pronephros
      during tailbud stages. FoxJ2 is expressed in the notochord and ventral portion of
      the neural tube. FoxQ1 is expressed specifically in the pharyngeal pouches as
      early as neurula stages and remains on in pharyngeal tissue throughout the
      tailbud stages. At later stages, FoxQ1 is also expressed in the anterior gut.
      FoxJ1.2, FoxJ2, and FoxQ1 may prove to be useful tissue-specific markers of these
      embryonic structures.

PMID- 16461018
TI  - Within-host dynamics of antigenic variation.
AB  - Genomes of some parasites contain dozens of alternative and highly diverged
      surface antigens, of which only a single one is expressed in any cell. Individual
      cells occasionally change expression of their surface antigen, allowing them to
      escape immune surveillance. These switches appear to occur in a partly random
      way, creating a diverse set of antigenic variants. In spite of this diversity,
      the parasitemia develops as a series of outbreaks, in which each outbreak is
      dominated by relatively few antigenic types. Host-specific immunity eventually
      clears the dominant antigenic types, and a new outbreak follows from antigenic
      types that have apparently been present all along at low frequency. This pattern
      of sequential dominance by different antigenic types remains unexplained. We
      review the five most prominent theories, which have developed mainly from studies
      of the protozoans Trypanosoma and Plasmodium, and the bacterial spirochete
      Borrelia. The most promising theories depend on some combination of mechanisms to
      create favored connectivity pathways through the matrix of transitions between
      variants. Favored pathways may arise from biased switches at the molecular level
      of gene expression or from biases imposed by immune selection. We illustrate the
      concept of connectivity pathways by reanalysis of data on transitions between
      variants from Borrelia hermsii.

PMID- 16461017
TI  - Association between SLC11A1 polymorphisms and susceptibility to different
      clinical forms of tuberculosis in the Peruvian population.
AB  - Polymorphism in SLC11A1 has been implicated in host susceptibility to
      tuberculosis. We have studied associations between INT4, D543N, and 3'UTR
      polymorphisms of SLC11A1 and different clinical forms of TB. Analysis used 507
      patients with pulmonary TB, 123 with extra pulmonary TB and 513 controls. INT4
      and D543N showed allelic association with pulmonary TB (P=0.02 and 0.03
      respectively). INT4-D543N-3'UTR haplotypes showed an association with pulmonary
      TB (P=0.03). No association of SLC11A1 with miliary TB was observed, and a
      possible association of D543N to the pleural form (P=0.08) was suggested. These
      results support association between SLC11A1 and TB, particularly to the common
      pulmonary form.

PMID- 16461019
TI  - Real-time assay of immobilized tannase with a stopped-flow conductometric device.
AB  - A stopped-flow manifold was developed to assay and characterize immobilized
      tannase (EC 3.1.1.20). The immobilized enzyme reactor was inserted within the
      tube-type electrode pair (cell constant=103.2 cm(-1)) for a real-time
      conductometric measurement. Tris buffer (2 mM, pH=7.0) was used as the carrier
      for sensitivity improvement. The activities and kinetic parameters (Km values)
      for propyl gallate, methyl gallate and tannic acid were investigated.

PMID- 16461020
TI  - Comparative ligand-binding analysis of ten human lipocalins.
AB  - At least ten different lipocalins occur in the human body: retinol-binding
      protein (RBP), alpha1-acid glycoprotein, alpha1-microglobulin, apolipoprotein D,
      beta-trace protein, complement component 8gamma, glycodelin, neutrophil
      gelatinase-associated lipocalin, odorant-binding protein, and tear lipocalin.
      Although many of these lipocalins seem to play an important physiological role,
      their precise biological function is not always clear. Especially the
      interpretation of their diverse ligand-binding activities has been hampered by
      the fact that the natural lipocalins were prepared from different sources and
      with varying purity. Here we present a generic expression and purification
      strategy for the recombinant lipocalins, which is based on secretion into the
      periplasm of E. coli, where disulphide bonds are readily formed, followed by
      affinity purification via the Strep-tag II and gel filtration. The ten human
      lipocalins were successfully prepared and their ligand-binding activities were
      compared via fluorescence titration with a set of typical ligands: retinol,
      retinoic acid (RA), 11-(5-(dimethylamino)-1-naphthalene-sulfonylamino)undecanoic
      acid (DAUDA), and 8-anilino-1-naphtalene-sulfonic acid (ANS). As result, merely
      two lipocalins, RBP and beta-trace, revealed high affinities both for retinol and
      for RA, which probably reflects a specialized physiological function in retinoid
      complexation. Surprisingly, the strongest retinol affinity was detected for
      apolipoprotein D, whereas this lipocalin exhibits much weaker binding activity
      for retinoic acid. Binding studies with the two spectroscopic probes DAUDA and
      ANS revealed mixed patterns, which demonstrates that the affinity for lipophilic
      substances varies considerably among human lipocalins. Notably, RBP with its
      perfectly moulded retinol-binding site did not show any detectable binding
      activity for both compounds. Hence, our recombinant expression and purification
      system should be useful for further structural and functional studies of
      lipocalins from human origin and beyond.

PMID- 16461021
TI  - Is there a role for immunotherapy in hepatocellular carcinoma?
AB  - Incidence of hepatocellular carcinoma has been rising in the last two decades
      because of the wide exposure to hepatitis C virus during 1960s and 1970s.
      Improvement in treatment has been achieved by local ablative therapies, however
      because of early recurrence and lack of effective chemotherapies, alternative
      treatments based on stimulation of the anti-tumour immune response could
      represent new strategies to control hepatocellular carcinoma spread and
      recurrence. Proof of principle of an effective immunotherapy has been achieved
      for other solid tumours such as melanoma and several results could be transferred
      to the immunotherapy of hepatocellular carcinoma. Specific tumour antigens have
      been identified in hepatocellular carcinoma, such as cancer testis antigens
      expressed in a large part of hepatocellular carcinomas and alpha-fetoprotein that
      has been already employed in clinical trials demonstrating immunogenicity without
      however significant clinical efficacy. Better results have been achieved by non
      antigen-specific immunotherapies that demonstrated improvement in recurrence and
      recurrence-free survival in patients undergoing surgical resection for
      hepatocellular carcinoma. Passive immunotherapy and targeted therapies blocking
      tumour cell receptors or enzymatic pathways are already in the clinic for other
      malignancies and the near future will see these new treatments applied to
      hepatocellular carcinoma patients along with the development of efficacious
      active immunotherapies aimed at reducing disease recurrence and improving
      survival.

PMID- 16461023
TI  - Hepatocellular carcinoma cells containing hepatitis B virus X protein have
      enhanced invasive potential conditionally.
AB  - AIMS: To establish a sustaining hepatitis B virus X protein expressed Chang liver
      cell line and to explore their biological behaviours of invasive potential
      induced by hepatitis B virus X protein. METHODS: Polymerase chain reaction was
      used to amplify the HBx gene from the whole hepatitis B virus genome. The gene
      was then subcloned into the eukaryotic expression vector pcDNA3.1 to construct
      the pcDNA3.1-HBx plasmid. Gene transfection mediated by Lipofectamine was used to
      introduce the plasmid into the human liver cell line Chang, and stable expression
      of the HBx gene was detected. RESULTS: HBx gene was cloned from the transfected
      Chang liver cells by reverse transcription-polymerase chain reaction, and
      confirmed by electrophoresis. The stably transfected Chang cells expressing HBx
      with malignant characteristics were verified and compared with control cells in
      terms of their growth curves, clonogenicity, wound healing abilities, migration
      and metastasis. CONCLUSION: The stabilising human liver cell lines Chang liver
      containing HBx gene expression have been established successfully. The invasive
      potential of Chang cells was conditionally enhanced by HBx transfection.

PMID- 16461024
TI  - Fulminant hepatic failure due to secondary amyloidosis.
AB  - Systemic amyloidosis frequently involves liver, however, clinically apparent
      liver disease is rare and, if observed, is usually mild. Rarely, primary
      amyloidosis may present with evidence of portal hypertension or hepatic failure.
      Although secondary amyloidosis may involve the liver and rarely causes liver
      pathologies such as cholestatic hepatitis and portal hypertension, to our
      knowledge, hepatic failure due to secondary amyloidosis has been reported once
      before. Herein, we presented a woman with subacute fulminant hepatic failure who
      had no known history of a chronic disease other than episodes of urinary tract
      infection, and secondary amyloidosis was diagnosed with post-mortem liver biopsy.

PMID- 16461025
TI  - Transanal endoscopic microsurgery in rectal adenomas: experience of six Italian
      centres.
AB  - BACKGROUND/AIMS: Transanal endoscopic microsurgery is a minimally invasive
      technique that allows the excision of benign and selected malignant tumours. We
      present a study for evaluating surgical morbidity, mortality and local recurrence
      rate of patients with rectal adenomas treated with transanal endoscopic
      microsurgery in six different Italian centres following the same protocol.
      METHODS: A total of 882 patients with rectal lesions (adenomas and early stage of
      carcinomas) underwent transanal endoscopic microsurgery in six different Surgical
      Departments from January 1993 to October 2004. Five hundred and ninety patients
      had preoperative diagnosis of adenomas but 588 patients were regularly followed
      up to determine treatment efficacy in terms of local recurrence rate. RESULTS:
      The study involved 588 patients, with a median age of 66 years (25th percentile
      75th percentile=58-71 years). No postoperative mortality was reported.
      Intraoperative complications were observed in three patients (0.5%). Minor
      complications occurred in 48 patients (8.2%) whereas major complications were
      found only in 7 patients (1.2%). Definitive histology confirmed adenomas in 530
      cases (90.1%). Two patients (0.3%) were lost to follow-up so were not included in
      the paper. At median follow-up of 44 months (25th percentile-75th percentile=15
      74 months), 23 (4.3%) adenomas recurred and were successfully retreated by
      transanal endoscopic microsurgery [20 cases (87%)] and by conventional surgery [3
      patients (13%)]. No further recurrences were observed at subsequent follow-up.
      Thirty-one (5.3%) patients died during follow-up for old age, cardiac disease,
      etc. CONCLUSIONS: Transanal endoscopic microsurgery is, in our experience, an
      effective method for local resection of benign rectal tumours with morbidity of
      11.4%, no postoperative mortality and with a percentage of local recurrence of
      4.3%.

PMID- 16461026
TI  - Psychological well-being of adult coeliac patients treated for 10 years.
AB  - BACKGROUND: Adults with longstanding coeliac disease generally report reduced
      quality of life. Uncertainty remains whether this is a sign of depression,
      thought to be a feature of the disorder. AIM: To assess the psychological well
      being in adults with long-treated coeliac disease. PATIENTS AND METHODS: Fifty
      one coeliac disease adults (59% women) aged 45-64 years diagnosed in 1984-1988
      and showing evidence of remission 8-12 years later were examined by the
      Psychological General Well-being index. One hundred and eighty-two (57% women)
      adults of same age served as population controls. RESULTS: The coeliac disease
      patients showed no more signs of anxiety, depressed mood or distress than the
      controls as assessed by the Psychological General Well-being index, 103 (95%
      confidence interval (95% CI)=99-107) versus 103 (95% CI=100-106). However, unlike
      controls, the coeliac disease women showed a significantly lower Psychological
      General Well-being index than the coeliac disease men, 97 (95% CI=91-103) versus
      111 (95% CI=106-117) (P<0.003). CONCLUSION: Long-treated adult coeliac disease
      patients showed no difference in psychological well-being to population controls,
      suggesting that signs of depressed mood is no feature of well-treated coeliac
      disease. The observation that coeliac disease women living in Sweden experience
      poorer outcome of treatment than coeliac disease men is a cause of concern and
      calls for further studies.

PMID- 16461027
TI  - On rising reflux and other matters.

PMID- 16461028
TI  - Prenatal identification of a marker chromosome 16 by chromosome microdissection
      and reverse FISH.
AB  - Prenatal cytogenetic analysis of cultured amniocytes was performed after an
      increased foetal nuchal translucency thickness was detected by ultrasound in week
      17 of a pregnancy. Analysis of GTG-banded chromosomes showed a small marker
      chromosome in six of the 12 colonies analysed. The supernumerary abnormal
      chromosome appeared to be positive with DA/DAPI staining and C-banding. The
      parents' karyotypes were normal. Using microFISH and FISH with band-specific
      probes, we found the marker appeared to be derived from chromosome region
      (16)(p13.1-->q12.2). Accurate identification of the marker chromosome was
      important for prenatal counselling: the marker chromosome contained euchromatic
      sequences, the foetus was carrying mosaic trisomy 16, and based on the literature
      the prognosis for the foetus was unfavourable and the pregnancy was terminated.

PMID- 16461029
TI  - Human laterality disorders.
AB  - Heterotaxia is a group of congenital disorders characterized by a misplacement of
      one or more organs according to the left-right axis. Bilateral asymmetry of
      internal organs is conserved among all vertebrate species. Analyses in animal
      models such as mouse, chicken, frog and zebrafish allowed for a remarkable
      progress of knowledge on the embryonic and genetic mechanisms underlying internal
      left-right asymmetry. In this review we focus on the insights from these model
      organisms that are useful for a better understanding of the etiology and
      pathogenesis of human heterotaxia. The known causes of human heterotaxia are
      reviewed and situated within the conceptual framework that originates from
      vertebrate model organisms. Furthermore, we attempt to apply the rapidly
      increasing insights gained from both animal models and human genetics to clinical
      practice in order to contribute to a more accurate conceptual classification,
      genetic diagnosis and counseling.

PMID- 16461030
TI  - Double aneuploidy (48,XXY,+21): molecular analysis demonstrates a maternal
      origin.

PMID- 16461031
TI  - Identification of a quantitative trait locus on rat chromosome 4 that is strongly
      linked to femoral neck structure and strength.
AB  - Risk factors for osteoporotic hip fracture include reduced bone mineral density
      and poor structure of the femoral neck, both of which are heritable traits.
      Previously, we showed that despite similar body size, Fischer 344 (F344) rats
      have significantly different skeletal traits compared with Lewis (LEW) rats. To
      identify a gene or genes regulating fracture risk at the femoral neck, we mapped
      quantitative trait loci (QTL) for femoral neck density and structure phenotypes
      using a 595 F2 progeny derived from the inbred F344 and LEW strains of rats.
      Femoral neck phenotypes included volumetric bone mineral density (vBMD), neck
      width, femoral neck cross-sectional area and polar moment of inertia (Ip). A 20
      cM genome-wide scan was performed using 118 microsatellite markers and linkage
      analysis was conducted to identify chromosomal regions harbor QTL for femoral
      neck phenotypes. Strong evidence of linkage (P<0.01) to femoral neck vBMD was
      observed on chromosomes (Chrs) 1, 2, 4, 5, 7, 10 and 15. QTL affecting femoral
      neck structure and biomechanical properties were detected only on Chr 4 where the
      F344 alleles were shown to improve femoral neck structure, whereas these alleles
      had no effect on bone measurements at the lumbar spine and only modest effects at
      the femoral midshaft. In contrast, QTL on Chrs 1, 2 and 10 affected multiple
      skeletal sites. Several QTL regions in this study are homologous to human
      chromosomal regions, where linkage to femoral neck and related phenotypes has
      been reported previously. These findings represent an important first step in
      localizing and identifying genes that influence hip fragility.

PMID- 16461032
TI  - Nature of phosphate substrate as a major determinant of mineral type formed in
      matrix vesicle-mediated in vitro mineralization: An FTIR imaging study.
AB  - Membrane-bound extracellular matrix vesicles play an important role in the de
      novo initiation and propagation of calcium-phosphate mineral formation in
      calcifying cartilage, bone, dentin, and in pathologic calcification.
      Characterization of the phase, composition, crystal size, and perfection provides
      valuable insight into the mechanism of the mineral deposition. In the present
      study, Fourier transform infrared imaging spectroscopy (FT-IRIS) was used to
      characterize the mineral phase generated during MV-mediated in vitro
      mineralization. FT-IRIS studies revealed that the mineral phase associated with
      MVs calcified in the presence of AMP and beta-GP was always found to be
      crystalline hydroxyapatite while with ATP only a small amount of immature
      mineral, most likely an amorphous or poorly crystalline hydroxyapatite, was
      observed. Low concentrations of pyrophosphate (PPi) (< or = 0.01 mM) showed
      apatitic mineral while high concentrations showed immature calcium pyrophosphate
      dihydrate (CPPD). The implications of these findings are that (a) hydrolysis of
      AMP or beta-GP, monophosphoester substrates of MV-5' AMPase (substrate: AMP) and
      TNAP (substrates: AMP, beta-GP), yields orthophosphate (Pi) which leads to the
      formation of mature crystalline, apatite mineral, while the hydrolysis of ATP,
      substrate for MV-TNAP or ATPase or NPP1, inhibits the formation of mature
      hydroxyapatite, and (b) pyrophosphate (PPi) has a bimodal effect on
      mineralization, i.e., at low PPi concentrations, alkaline phosphatase activity of
      matrix vesicles is able to hydrolyze PPi to orthophosphate and thus facilitates
      the formation of basic calcium phosphate mineral which subsequently transforms
      into apatitic mineral. We hypothesize that, at high PPi concentrations, PPi by
      itself or Pi released by partial PPi hydrolysis could act as inhibitors of
      alkaline phosphatase activity, thereby preventing complete hydrolysis of PPi to
      Pi, and thus resulting in the accumulation of calcium pyrophosphate dihydrate.
      Therefore, in order for physiological mineralization to proceed, a balance is
      required between levels of Pi and PPi.

PMID- 16461033
TI  - Frequency and consequences of recording an electrocardiogram >10 minutes after
      arrival in an emergency room in non-ST-segment elevation acute coronary syndromes
      (from the CRUSADE Initiative).
AB  - We sought to determine the frequency of electrocardiographic (ECG) acquisition
      within 10 minutes of hospital arrival, factors associated with delayed ECG
      acquisition, and any relation among delayed ECG acquisition, treatment patterns,
      and clinical outcomes. We therefore analyzed data from 63,478 patients (26,615
      women, 42%) with high-risk non-ST-segment elevation acute coronary syndromes
      (designated by positive cardiac markers and/or ischemic ST-segment changes) who
      were enrolled in the CRUSADE Quality Improvement Initiative from February 2001 to
      March 2004. Patients were categorized based on time to electrocardiography as
      delayed (>10 minutes from hospital arrival) or nondelayed (<10 minutes).
      Multivariable predictors of delayed ECG acquisition were determined. Overall,
      median time to electrocardiography was 15 minutes (25th to 75th percentile 7 to
      32). ECG acquisition was delayed (median 25 minutes, 25th to 75th percentile 16
      to 50) in 41,397 patients (65.2%). In the remaining 34.8%, time to
      electrocardiography was <10 minutes (median 5 minutes, 25th to 75th percentile 3
      to 8). Women were more likely than men to have delayed ECG acquisition (69% vs
      62%), and female gender was the most significant predictor of delayed ECG
      acquisition (odds ratio 1.29, 95% confidence interval 1.25 to 1.34). In
      conclusion, only 33% of high-risk patients with non-ST-segment elevation acute
      coronary syndrome had an initial electrocardiogram obtained <10 minutes of
      arrival as recommended. Women were significantly more likely than men to have
      delayed ECG acquisition. Emergency departments should focus on decreasing the
      time to initial ECG acquisition to improve treatment of acute coronary syndrome
      in this group.

PMID- 16461034
TI  - Concordance of electrocardiographic patterns and healed myocardial infarction
      location detected by cardiovascular magnetic resonance.
AB  - Q-wave myocardial infarction (MI) location is generally based on a pathologic
      correlation first proposed >50 years ago. Despite the proved reliability of
      contrast-enhanced cardiovascular magnetic resonance (CE-CMR) imaging to detect
      and locate infarcted areas, no global study has been conducted with the aim of
      correlating the electrocardiographic (ECG) patterns of Q-wave MI with infarct
      location. We studied this correlation in 51 patients with ST-elevation acute
      coronary syndrome who presented with Q waves or equivalents during MI. Seven
      preestablished ECG patterns that matched with high specificity to 7 different MI
      locations as detected by CE-CMR imaging were used to assess its value in clinical
      practice to locate an infarcted area. There were 4 ECG patterns in the
      anteroseptal zone (23 patients; septal, apical, and/or anteroseptal, extensive
      anterior, and limited anterolateral) and 3 ECG patterns in the inferolateral zone
      (28 patients; lateral, inferior, and inferolateral). In conclusion, (1) the
      predefined ECG patterns we used matched well (86% global concordance) with their
      corresponding infarction areas as detected by CE-CMR imaging and have real value
      in clinical practice, and (2) the RS morphology in lead V(1) is due to lateral MI
      and the QS morphology in lead aVL is due to mid-anterior and mid-lateral MI.
      Therefore, the terms posterior and high lateral infarction are incorrect and
      should be changed to lateral wall and limited anterolateral wall MI.

PMID- 16461035
TI  - Relation of end-diastolic wall thickness and the residual rim of viable
      myocardium by magnetic resonance imaging to myocardial viability assessed by
      fluorine-18 deoxyglucose positron emission tomography.
AB  - End-diastolic wall thickness (EDWT) and thickness of the residual non-contrast
      enhanced myocardial rim have been suggested as markers for the assessment of
      myocardial viability by cardiovascular magnetic resonance (CMR) imaging. This
      study compared these parameters as derived from contrast-enhanced CMR images for
      the prediction of myocardial viability as determined by fluorine-18 deoxyglucose
      positron emission tomography (FDG-PET). Twenty-two patients with ischemic
      cardiomyopathy (ejection fraction 31 +/- 11%) were investigated. For contrast
      enhanced CMR imaging, a standard inversion-recovery sequence was used. FDG-PET
      was performed using a hyperinsulinemic-euglycemic clamp. Data were analyzed with
      a 17-segment model. Of 146 severely dysfunctional segments, 112 were assessed as
      viable and 34 as nonviable by nuclear imaging. Using receiver-operator
      characteristic analysis, areas under the curve were 0.95 for unenhanced
      myocardial rim (95% confidence interval 0.92 to 0.98) and 0.86 for EDWT (95%
      confidence interval 0.80 to 0.93, p <0.001 vs unenhanced myocardial rim) for the
      prediction of viability as assessed by FDG-PET. Cutoffs of 5.4 mm for EDWT and
      3.0 mm for unenhanced myocardial rim were found to optimally differentiate
      viability by FDG-PET. In 25 segments with divergent results, 94% of segments with
      an EDWT < or =5.4 mm and an unenhanced myocardial rim >3.0 mm were scored as
      viable by FDG-PET, whereas 57% of segments with an EDWT >5.4 mm and an unenhanced
      myocardial rim < or =3.0 mm were scored nonviable with the reference technique.
      In conclusion, unenhanced myocardial rim is superior to EDWT for the prediction
      of myocardial viability as determined by FDG-PET and may be clinically useful for
      assessment of myocardial viability in patients with ischemic cardiomyopathy and
      regional wall thinning.

PMID- 16461036
TI  - Comparison of mortality patterns in patients with ST-elevation myocardial
      infarction arriving by emergency medical services versus self-transport (from the
      prospective Ottawa Hospital STEMI Registry).
AB  - Emergency medical services (EMSs) play a key role in the recognition and
      treatment of ST-elevation of myocardial infarction (STEMI). We sought to
      determine contemporary use of EMS in patients with STEMI and its relation to
      treatment, morbidity, and mortality patterns. Patients who arrived by EMS were
      compared with those who arrived by self-transport. Among 401 patients, 59.9%
      arrived by EMS and 40.1% by self-transport. Patients who arrived by EMS were
      older (p <0.001) and had higher Killip's scores (p <0.001). Door-to-needle and
      door-to-balloon intervals were shorter in patients who arrived by EMS (42 vs 57
      minutes, p <0.001, and 124 vs 154 minutes, p <0.001, respectively). In-hospital
      mortality was higher in patients who used EMS (13.3% vs 5.0%, p <0.001). Patients
      who arrived by EMS also had higher mortality within the first hour of hospital
      arrival (4.2% vs 0%, p = 0.007). Multivariate analysis showed that only age and
      systolic blood pressure were predictors of mortality. Despite faster onset of
      reperfusion therapy in patients who arrived by EMS, mortality was higher. Almost
      33% of these deaths occurred in the early in-hospital period, which was due to
      older and sicker patients having the tendency to come by EMS. Our results suggest
      that regional approaches are needed to trigger earlier reperfusion therapy in
      patients with STEMI who use EMS.

PMID- 16461037
TI  - Enhanced sensitivity of dobutamine stress echocardiography by observing wall
      motion abnormalities during the recovery phase after acute beta-blocker
      administration.
AB  - Dobutamine stress echocardiography (DSE) has a modest sensitivity for detecting
      single-vessel coronary artery disease (CAD). This study assessed the additional
      diagnostic value of new or worsening wall motion abnormalities during recovery
      after acute administration of beta blockers. The study population consisted of
      200 patients (mean 59 +/- 11 years of age, 144 men), who underwent DSE. Images
      were acquired at rest, low dose, peak dose, and during recovery. Patients
      received intravenous metoprolol (1 to 5 mg/min). The dose was adjusted to achieve
      a recovery heart rate within a 10% range of heart rate at rest. Coronary
      angiography was performed within 2 months. Inducible new wall motion
      abnormalities were observed in 168 patients (84%) at peak stress. An additional
      14 patients (7%) developed new or worsening wall motion abnormalities during
      recovery. CAD was detected in 182 patients (86 had single-vessel CAD).
      Sensitivity, specificity, and accuracy of DSE were 88%, 65%, and 73% at peak
      stress and 97%, 65%, and 74% during recovery. Sensitivity was particularly higher
      during recovery than during peak stress in patients with single-vessel CAD (98%
      vs 81%, p <0.001). In conclusion, assessment of wall motion abnormalities during
      the recovery phase after acute beta blockade improves sensitivity of DSE,
      particularly in patients with single-vessel CAD.

PMID- 16461038
TI  - Relation between on-treatment increments in serum high-density lipoprotein
      cholesterol levels and cardiac mortality in patients with coronary heart disease
      (from the Bezafibrate Infarction Prevention trial).
AB  - This study evaluated the association between changes in serum levels of high
      density lipoprotein (HDL) cholesterol that occur under bezafibrate therapy and
      cardiac mortality in patients with coronary heart disease (CHD) who were enrolled
      in the Bezafibrate Infarction Prevention trial. We compared serum levels of HDL
      cholesterol in 1,509 patients in tertiles of on-treatment increments with those
      of 1,517 patients in the placebo group. Long-term follow-up showed that cardiac
      mortality decreased significantly with increasing tertiles of on-treatment change
      in HDL cholesterol (9.5%, 6.6%, and 6.3% of patients tertiles 1, 2, and 3,
      respectively, died of cardiac causes, p for trend = 0.02). In multivariate
      analysis, the magnitude of on-treatment increment of HDL cholesterol was
      independently associated with a decreased risk of cardiac death (hazard ratio
      1.05, 95% confidence interval 0.74 to 1.47, for tertile 1; hazard ratio 0.73, 95%
      confidence interval 0.50 to 1.07, for tertile 2; hazard ratio 0.65, 95%
      confidence interval 0.43 to 0.97, for tertile 3, compared with placebo-allocated
      patients, p for trend = 0.02). Analyzing the association with change in HDL
      cholesterol as a continuous variable showed that the risk of cardiac mortality
      was decreased by 27% for every 5-mg/dl increase in on-treatment change in HDL
      cholesterol (p <0.001). In conclusion, although a definite secondary prevention
      effect of bezafibrate could not be found when examining the intervention group as
      a whole, our findings are consistent with a possible independent association
      between an increase in HDL cholesterol with bezafibrate therapy and a decrease in
      cardiac mortality. In appropriately selected patients, monitoring short-term
      response to bezafibrate therapy through change in HDL cholesterol may indicate
      the potential long-term benefit of the drug.

PMID- 16461040
TI  - Benefits of niacin in patients with versus without the metabolic syndrome and
      healed myocardial infarction (from the Coronary Drug Project).
AB  - This post hoc analysis from the Coronary Drug Project (CDP) evaluated the effects
      of niacin monotherapy on clinical outcomes in patients with and without the
      metabolic syndrome (MS). The CDP was a randomized, placebo-controlled clinical
      trial of lipid-modifying agents in men with previous myocardial infarction (MI).
      Of the 5 drug regimens, only niacin significantly decreased definite recurrent
      nonfatal MI at 6 years and total mortality at a 15-year follow-up. Patients
      treated with niacin (n = 1,119) and placebo (n = 2,787) were grouped according to
      the presence or absence of the MS at baseline. The MS was defined on the basis of
      meeting > or =3 of 5 criteria from the current National Cholesterol Education
      Program guidelines in a small subgroup of patients with high-density lipoprotein
      cholesterol determinations at baseline and on the basis of > or =3 of 4 criteria
      in the total population, excluding the high-density lipoprotein cholesterol
      criterion. Niacin decreased the occurrence of 6-year MI and 15-year total
      mortality similarly among patients with or without the MS. For example, in the
      total population, 15-year total mortality rates were 60% and 64% (hazard ratio
      0.86) in patients with the MS treated with niacin and placebo, respectively, and
      50% and 57% (hazard ratio 0.86) in those without the MS (Z for interaction =
      0.06, indicating homogeneity of the treatment effect across groups). In
      conclusion, these results support the use of niacin in postinfarction patients
      with and without the MS.

PMID- 16461039
TI  - Relation of various plasma growth factor levels in patients with stable angina
      pectoris and total occlusion of a coronary artery to the degree of coronary
      collaterals.
AB  - We assessed (1) angiogenic factors in patients with stable angina and
      longstanding (> or =24 months) total occlusion of a single coronary artery and
      (2) the relation between plasma levels of angiogenic factors and the development
      of collateral vessels as evaluated by coronary angiography. Plasma concentrations
      of vascular endothelial growth factor (VEGF(165)), fibroblast growth factor,
      placenta-derived growth factors (PlGFs), and hepatocyte growth factor were
      assessed in 96 patients with stable angina and longstanding (> or =24 months)
      total occlusion of a single coronary artery. According to coronary angiographic
      results, 18 patients had no visible collaterals (group 0), 21 patients had
      visible collaterals but no filling of the recipient epicardial vessel (group 1),
      and 57 patients showed filling (partial or complete) of the recipient epicardial
      vessel by collaterals (group 2). Plasma VEGF(165) and PlGF concentrations were
      higher in group 1 than in groups 0 and 2 (VEGF(165) 75 pg/ml, range 24 to 105, vs
      23 pg/ml, range 15 to 29, and 19 pg/ml, range 10 to 41, respectively, F = 5.53, p
      = 0.006; PlGF 35 pg/ml, range 3.5 to 105, vs 1 pg/ml, range 1 to 38, and 1 pg/ml,
      range 1 to 5, respectively, F = 7.09, p = 0.008). Plasma VEGF(165) and PlGF
      levels were similar in groups 0 and 2. There was no significant difference in
      plasma levels of fibroblast and hepatocyte growth factor concentrations across
      the 3 groups. In conclusion, plasma levels of angiogenic growth factors differ
      among patients with stable angina pectoris and longstanding total coronary
      occlusion.

PMID- 16461041
TI  - Frequency of sudden cardiac death among acute myocardial infarction survivors
      with optimized medical and revascularization therapy.
AB  - The epidemiologic pattern of sudden cardiac death (SCD) may have changed in the
      modern treatment era of patients after an acute myocardial infarction (AMI). We
      evaluated the effect of optimized medical and revascularization therapy on the
      incidence of SCD after an AMI. A total of 2,130 consecutive patients (mean age 59
      +/- 10 years) with an AMI from 2 European centers (Germany and Finland) was
      included in the study. In this population, 1,004 patients (47%) were treated with
      an optimized medical and revascularization strategy (defined as treatment with
      revascularization, beta blockers, aspirin, statins, and angiotensin-converting
      enzyme inhibitors). Nonoptimized treatment, defined as a lack of any optimized
      treatment, was received by 1,126 patients (53%). During the mean follow-up of 2.9
      +/- 1.3 years, the incidence of SCD was very low among patients who received
      optimized treatment (1.2%, annual incidence 0.4%) compared with those who did not
      (3.6%, annual incidence 1.4%, p <0.01). The treatment strategy that had the
      greatest effect on differences in the SCD rate was revascularization therapy,
      with the hazard ratio of SCD being 2.1 (95% confidence interval 1.2 to 3.7, p
      <0.01) for SCD among nonrevascularized patients. Nonoptimized treatment was more
      often received by older patients, women, diabetic patients, and those with
      depressed left ventricular function. In conclusion, the incidence of SCD is low
      in the modern treatment era of patients after an AMI. Coronary revascularization
      seems to have a great effect on altered the epidemiologic pattern of SCD.

PMID- 16461042
TI  - Effectiveness of manual pressure hemostasis following transfemoral coronary
      angiography in patients on therapeutic warfarin anticoagulation.
AB  - We evaluated the effectiveness of manual pressure hemostasis after transfemoral
      coronary angiography in patients on therapeutic warfarin anticoagulation
      (international normalized ratio [INR] 2.0 to 3.0) compared with discontinuing
      warfarin > or =48 hours before the procedure (INR <2.0). There was a low
      incidence of small hematomas with either strategy (no significant difference) and
      no major vascular complications. No prolonged hospital stay due to an access site
      complication was observed, and no thromboembolic events occurred. In conclusion,
      transfemoral coronary angiography appears to be safe in patients on warfarin with
      an INR of 2.0 to 3.0).

PMID- 16461043
TI  - Variability in extent of platelet function inhibition after administration of
      optimal dose of glycoprotein IIb/IIIa receptor blockers in patients undergoing a
      high-risk percutaneous coronary intervention.
AB  - The Ultegra Rapid Platelet Function Assay was used to measure the inhibition of
      platelet aggregation at baseline and 10 minutes and 8 hours after starting
      therapy in 114 patients undergoing high-risk percutaneous coronary intervention
      with the planned use of a glycoprotein IIb/IIIa inhibitor. The abciximab-treated
      patients received a 0.25 mg/kg bolus, followed by a 0.125 microg/kg/min infusion
      for 12 hours; the eptifibatide-treated patients received 2 boluses of 180
      microg/kg administered 10 minutes apart, followed by a 2 microg/kg/min infusion
      for 24 hours; the tirofiban-treated patients received a 25 microg/kg bolus,
      followed by a 0.15 microg/kg/min infusion for 18 hours. Ten minutes after
      starting therapy, the mean level of platelet inhibition was 86 +/- 9% for
      abciximab, 92 +/- 6% for eptifibatide, and 95 +/- 5% for tirofiban (p <0.001); >
      or =95% platelet inhibition was achieved in 29% of the patients treated with
      abciximab, 44% of those receiving eptifibatide, and 68% of the those receiving
      tirofiban (p = 0.02). In conclusion, at the evaluated doses, tirofiban seemed to
      be the most effective drug in achieving "optimal" platelet inhibition very early
      after percutaneous coronary intervention.

PMID- 16461045
TI  - Angiographic pattern of restenosis following implantation of overlapping
      sirolimus-eluting (Cypher) stents.
AB  - Sirolimus-eluting stents (Cypher) have been shown to reduce the frequency of
      neointimal hyperplasia and restenosis compared with bare metal stents. However,
      the clinical implication of overlapping stents with regard to the pattern of
      restenosis is unclear. All patients who underwent angiography at our institution
      from May 2003 to March 2005 who had previously received 2 overlapping Cypher
      stents in native coronary lesions and had binary restenosis were included in our
      study. Quantitative coronary analysis was performed to determine the degree and
      location of the restenotic lesion with respect to the overlapping stented
      segment. The primary end point was to determine how often restenotic lesions
      occurred at the overlapped segment versus the nonoverlapped stented segments.
      During the study, 11 patients fit the inclusion criteria for our study; 91% were
      men and 55% had diabetes mellitus. The mean total stent length was 33.7 +/- 8.2
      mm. The mean length of the overlapped segment was 5.9 +/- 3.8 mm, equating to 19
      +/- 16% of the total stented area. The average time to follow-up angiography was
      277 +/- 126 days. All 11 lesions exhibited type 1 (focal) restenosis. Of these 11
      lesions, 10 had focal restenosis at the overlapped segment (p = 0.01, binomial
      test). The single case involving in-stent restenosis in the nonoverlapped segment
      occurred at the proximal stent edge. In conclusion, the pattern of restenosis
      observed in our study suggests a higher relative incidence of binary restenosis
      in the overlapped stented segment in patients who receive 2 overlapping Cypher
      stents.

PMID- 16461044
TI  - Comparison between sirolimus- and paclitaxel-eluting stent in T-cell subsets
      redistribution.
AB  - We sought to investigate the effects of 2 different coronary drug-eluting stents
      on the distribution of central or effector memory T cells circulating in the
      coronary sinus of patients with coronary artery disease who underwent
      percutaneous coronary revascularization. We randomly assigned 43 patients (mean
      age 65.4 +/- 4.3 years; 34 men) presenting with stable coronary disease and
      angiographically proved stenosis of the left anterior descending artery to
      treatment with sirolimus- or paclitaxel-eluting stents. Heparinized blood samples
      were obtained from the coronary sinus before and 20 minutes after stent
      implantation. Analysis of surface phenotype was performed by 4-color flow
      cytometry, and data are expressed as the percentage of positive cells. The
      percentages of CD8+ and CD4+ effector memory T cells, as defined by the
      CD3+CD45RO+CD27- phenotype, were significantly reduced in patients who received a
      sirolimus-eluting stent compared with the basal values. Conversely, the
      percentages of CD8+, but not CD4+, central memory T cells (CD3+CD45RO+CD27+) were
      increased in the same treatment group after the revascularization procedure. No
      changes in the percentages of memory T-cell populations in the paclitaxel-eluting
      stent group were observed. These findings show that sirolimus-eluting stents
      rapidly induced a redistribution of memory T lymphocytes, with a significant
      decrease of proinflammatory effector memory T cells circulating within the
      coronary sinus.

PMID- 16461046
TI  - Failure to retrieve undeployed paclitaxel-eluting coronary stents.
AB  - Following the observation of difficulty in retrieving undeployed paclitaxel
      eluting coronary stents (Taxus), we performed a retrospective analysis of 1,415
      consecutive percutaneous coronary interventions and addressed the frequency of
      damaged or lost undeployed coronary stents. The incidence for Cypher, Taxus, and
      bare metal stents was 0%, 1.5%, and 0.3%, respectively (p = 0.0007). In the 11
      cases involving Taxus stents, the treated vessel was invariably severely tortuous
      and/or calcified. The device was successfully retrieved despite being damaged
      and/or dislodged from the stent balloon in 5 cases; in 6 cases, stent
      embolization occurred. The clinical consequences were chronic claudication due to
      lower extremity device embolization in 1 patient and urgent surgical stent
      removal in 1 patient.

PMID- 16461047
TI  - Predictors of restenosis after placement of drug-eluting stents in one or more
      coronary arteries.
AB  - Although drug-eluting stents (DESs) have been increasingly used in a wide variety
      of clinical and anatomic situations, limited data are available regarding the
      predictors of DES failure in unselected lesions. We investigated the incidence
      and predictors of restenosis after implantation of DESs in routine clinical
      practice. A total of 1,795 consecutive patients underwent successful implantation
      of sirolimus-eluting (1,374 patients, 1,788 lesions) or paclitaxel-eluting (421
      patients, 517 lesions) stents. Of the 1,743 eligible patients (2,221 lesions),
      follow-up angiography at 6 months was obtained for 1,228 patients (70.5%, 1,577
      lesions). All data were prospectively recorded and analyzed to predict the
      occurrence of restenosis, defined as a diameter stenosis of > or =50%. Restenosis
      was documented in 125 patients with 138 lesions (8.8%), and target lesion
      revascularization was required in 70 patients with 82 lesions (5.2%). The pattern
      of restenosis was 85 focal (62%), 29 diffuse (21%), 11 diffuse proliferative
      (8%), and 13 total (9%). Lesion length, stent length, postintervention minimal
      lumen diameter, preintervention minimal lumen diameter, reference artery size,
      complex lesions, and use of a paclitaxel-eluting stent were univariate predictors
      of restenosis. Multivariate analysis showed that the use of a paclitaxel-eluting
      stent (odds ratio [OR] 4.37, 95% confidence interval [CI] 2.90 to 6.58, p
      <0.001), postintervention minimal lumen diameter (OR 0.32, 95% CI 0.20 to 0.50, p
      <0.001), and lesion length (OR 1.02, 95% CI 1.01 to 1.04, p <0.001) were
      independent predictors of restenosis. In conclusion, the rate of restenosis after
      DES implantation in routine clinical practice was similar to the rate reported in
      clinical trials, confirming the efficacy of DES in routine clinical practice.

PMID- 16461048
TI  - Prevalence and determinants of electrocardiographic left ventricular hypertrophy
      among a multiethnic population of postmenopausal women (The Women's Health
      Initiative).
AB  - Our objectives were to determine the prevalence and factors related to left
      ventricular hypertrophy (LVH) among older women for commonly used
      electrocardiographic criteria. LVH is a potent risk factor for cardiovascular
      disease, especially among women. However, its value has been limited, in part, by
      the use of different electrocardiographic criteria and the lack of a clearly
      defined standard for the general population. A total of 3,613 eligible women,
      aged 50 to 79 years, underwent medical history, physical measurements, and
      biochemical determinations and had behavioral factors recorded at baseline. Three
      LVH indexes were derived from computer measurement of the electrocardiogram:
      hypertrophied left ventricular mass > or =171.04 g (HLVM); Cornell voltage > or
      =2,200 microV; and Minnesota Code items. The prevalence of LVH ranged from <1% to
      13% when stratified by age, ethnicity, and scoring technique. Baseline traits
      differed significantly for those meeting the LVH criteria. Predictors (p <0.01)
      of HLVM were age (odds ratio 0.66), height (odds ratio 1.47), waist/hip ratio
      (odds ratio 1.30), systolic blood pressure (odds ratio 1.18); low-density
      lipoprotein cholesterol (odds ratio 0.97), log insulin (odds ratio 2.10), dietary
      kilocalories (odds ratio 1.16), weekly energy expenditure (odds ratio 0.53),
      hypertension (odds ratio 1.61), current estrogen use (odds ratio 0.60), and
      current smoker (odds ratio 0.47). The presence of the metabolic syndrome was
      related to all LVH indexes, with odds ratios of 4.95, 2.24, and 2.35,
      respectively, for HLVM, Cornell voltage, and Minnesota Code. In conclusion, the
      prevalence of LVH varied by ethnicity and the electrocardiographic index used.
      However, the baseline traits, especially the factors associated with the
      metabolic syndrome, were consistently and strongly related to all LVH indexes,
      particularly HLVM. Intervention on these factors may provide strategies for
      reducing LVH, a strong independent risk factor for cardiovascular morbidity and
      mortality among women.

PMID- 16461049
TI  - Effect of raloxifene on cardiovascular adverse events in postmenopausal women
      with osteoporosis.
AB  - The impact of selective estrogen receptor modulators on cardiovascular disease
      outcomes in postmenopausal women remains unclear. This analysis assessed the
      effect of raloxifene on the incidence of cardiovascular adverse events in
      postmenopausal women followed for < or =8 years as participants in a 4-year
      osteoporosis treatment trial and a subsequent 4-year follow-up trial. The
      Continuing Outcomes Relevant to Evista (CORE) trial, designed to determine the
      effect of raloxifene on the incidence of invasive breast cancer, was a 4-year
      follow-up study to the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE)
      osteoporosis treatment trial. Of the 7,705 participants originally enrolled in
      MORE, 4,011 were enrolled in CORE and thus participated in both trials (MORE-CORE
      participants). The incidence of serious cardiovascular (i.e., coronary and
      cerebrovascular) adverse events during 8 years, confirmed by external
      adjudication in the 2 trials, was compared between treatment groups using Cox
      proportional hazards models. The 8-year incidence of serious cardiovascular
      adverse events did not differ significantly between the raloxifene (5.5%) and
      placebo (4.7%) groups (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.86
      to 1.56). Similar results were obtained when coronary (HR 1.22, 95% CI 0.82 to
      1.83) or cerebrovascular (HR 1.19, 95% CI 0.78 to 1.84) events were analyzed
      separately, and when cardiovascular events were analyzed in the 459 MORE-CORE
      participants who were at increased risk of cardiovascular events by previously
      established criteria (HR 1.03, 95% CI 0.58 to 1.82). In conclusion, we found no
      evidence of a beneficial or harmful effect of raloxifene on the incidence of
      cardiovascular events overall, or coronary or cerebrovascular events, in
      postmenopausal osteoporotic women at relatively low risk of cardiovascular
      events.

PMID- 16461050
TI  - Carotid artery stiffness in obese children with the metabolic syndrome.
AB  - Obesity and overweight have been associated with increased carotid intima-media
      thickness and stiffness in adults and children. Overweight and obesity have also
      been associated with an increased prevalence of the metabolic syndrome (MS). The
      aim of the study was to test the hypothesis that obese children with the MS have
      increased rigidity of their arteries compared with obese children without the MS.
      We studied 100 obese children (age range 6 to 14 years; 61 males, 39 females)
      consecutively seen in the outpatient clinic of a hospital department of
      pediatrics. Anthropometric measures and biochemical tests were performed in all
      children. Quantitative B-mode ultrasound scans were used to measure intima-media
      thickness and diameters of the common carotid artery. Common carotid arterial
      stiffness was significantly higher in the group of obese children with the MS (n
      = 38) at 1.29 +/- 0.06 mm (values log transformed) versus 1.12 +/- 0.04 mm (p
      <0.03) compared with those without the MS (n = 62). These differences persisted
      even after adjustment for age, gender, and C-reactive protein. Obese children
      with the MS had significantly higher plasma concentrations of C-reactive protein
      (1.57 +/- 0.06 microg/L, values log transformed) compared with obese children
      without the MS (1.38 +/- 0.05 microg/L, p <0.03). In conclusion, obese children
      who met the diagnostic criteria for the MS had higher common carotid artery
      stiffness and higher C-reactive protein plasma concentrations than obese children
      without the MS.

PMID- 16461052
TI  - Patterns and predictors of warfarin use in patients with new-onset atrial
      fibrillation from the FRACTAL Registry.
AB  - Warfarin is underused for stroke prevention in atrial fibrillation (AF). Previous
      studies addressing this have lacked longitudinal assessment. This study sought to
      characterize contemporary warfarin use in new-onset AF and evaluate its change
      over time. It was hypothesized that AF recurrence has an important influence on
      warfarin use patterns. One thousand five adults from 17 centers in the United
      States and Canada were enrolled into a prospective observational registry after
      their first documented episodes of AF. Detailed demographic, clinical history,
      and management data were collected on all subjects at enrollment, including
      medication use. Patients were followed at regular intervals for interim events
      and changes in AF management. Warfarin use at baseline and last follow-up (mean
      25 +/- 8 months) after enrollment was modeled using multivariate analysis.
      Initially, 65% of subjects were prescribed warfarin, but only 44% were taking it
      at 30 months. Even in "ideal" candidates for warfarin, the rate of warfarin
      prescription decreased from 70% at baseline to 50% at 30 months. Stroke risk
      factors, including hypertension, congestive heart failure, valvular heart
      disease, and previous stroke or transient ischemic attack were significant
      predictors of warfarin prescription at baseline. At last follow-up, the relation
      between AF recurrence and warfarin use (odds ratio 2.3, 95% confidence interval
      1.6 to 3.1) was stronger than that for any individual stroke risk factor. In
      conclusion, predictors of warfarin use in patients with AF include AF recurrence
      and selected stroke risk factors. The discontinuation of warfarin in a large
      number of patients with AF over time is a cause for concern in light of data from
      recent clinical trials.

PMID- 16461051
TI  - Selective induction of matrix metalloproteinases and tissue inhibitor of
      metalloproteinases in atrial and ventricular myocardium in patients with atrial
      fibrillation.
AB  - Atrial fibrillation (AF) produces changes in atrial structure and extracellular
      matrix composition, which is regulated by matrix metalloproteinases (MMPs).
      Moreover, AF often occurs in the setting of congestive heart failure (CHF), which
      also affects MMPs. Whether changes in MMPs or the tissue inhibitors of
      metalloproteinases (TIMPs) within atrial and ventricular myocardium are
      differentially regulated with AF remains unclear. Myocardium from the walls of
      the right atrium, right ventricle, left atrium, and left ventricle was obtained
      from the explanted hearts of 43 patients with end-stage CHF. AF was present in 23
      patients (duration 1 to 84 months). The remaining 20 patients served as non-AF
      controls. The groups were well matched clinically, but left atrial (LA) size was
      increased in the AF cohort (5.5 +/- 0.8 vs 4.9 +/- 0.7 cm, p <0.05). Myocardial
      collagen content and levels of MMP-1, -2, -8, -9, -13, and -14, and TIMP-1, -2, 
      3, and TIMP-4 were determined. With AF, collagen content was greater within the
      atrial myocardium but less in the ventricular myocardium. There were chamber
      specific differences in MMPs and TIMPs with AF. For example, MMP-1 in the right
      atrium and MMP-9 in the left atrium were greater with AF. TIMP-3 levels were
      greater in the right ventricle, left atrium, and left ventricle. Although total
      LA collagen was positively correlated with AF duration (r = 0.49, p <0.03), there
      was an inverse relation between soluble collagen I and AF duration (n = 6, r = 
      0.84, p <0.04). In conclusion, AF is associated with chamber-specific alterations
      in myocardial collagen content and MMP and TIMP levels, indicative of
      differential remodeling and altered collagen metabolism. Differences in MMP and
      TIMP profiles may provide diagnostic and mechanistic insights into the
      pathogenesis of AF with CHF.

PMID- 16461053
TI  - Relation of advanced heart failure symptoms to risk of inappropriate
      defibrillator shocks.
AB  - Inappropriate implantable cardioverter-defibrillator (ICD) shocks continue to be
      a major source of distress to patients and a drain on the health care system.
      Expanding indications for ICD implantation include a large portion of patients
      with heart failure. This study investigated the relation between inappropriate
      ICD shocks and the severity of heart failure symptoms. Predictors of the time to
      first inappropriate ICD therapy were investigated in 230 consecutive patients
      implanted in 2001 and 2002. Thirty-two patients received 42 inappropriate shocks
      during a median follow-up of 501 days. Inappropriate shocks were due to atrial
      fibrillation (AF) or tachycardia (n = 31), other supraventricular tachycardias
      (n= 6), sinus tachycardia (n = 3), and noise or double counting (n = 2). The time
      to first inappropriate ICD shock was earliest in patients with advanced classes
      of heart failure (1- and 2-year shock-free survival of 79% and 70% for patients
      in New York Heart Association [NYHA] class III or IV vs 92% and 88% for patients
      in NYHA class I or II, respectively, p = 0.02). After correcting for age, gender,
      the presence of coronary artery disease, the presence of AF, the use of beta
      blockers, and indication for ICD implantation in a Cox regression model, advanced
      heart failure (NYHA class III or IV) remained an independent predictor of first
      inappropriate ICD shocks (hazard ratio 2.7, p = 0.01). Other predictors of the
      time to first inappropriate ICD shock included the presence of AF as the baseline
      rhythm at the time of the ICD implantation and the absence of coronary disease.
      In conclusion, inappropriate ICD shocks are predominantly due to AF. Advanced
      heart failure is an independent predictor of the time to first inappropriate ICD
      shocks. The effect of ICD programming and antiarrhythmic drug therapy on the
      incidence of inappropriate shocks deserves further investigation.

PMID- 16461054
TI  - Effects of dietary omega-3 fatty acid supplementation on endothelium-dependent
      vasodilation in patients with chronic heart failure.
AB  - We investigated the effects of omega-3 fatty acids administration on endothelium
      dependent vasodilation in patients > or =65 years old who received treatment for
      chronic heart failure (CHF). Twenty patients (mean age 73 years; 15 men) with
      grade II and III CHF who were on maximal medical management were recruited.
      Patients were randomized in a double-blind, crossover fashion to 6 weeks of omega
      3 fatty acid (1.8 g ecosapentaenoic acid and 1.2 g docosahexaenoic acid) or olive
      oil. Forearm blood flow (FBF) responses to incremental doses of intra-arterial
      sodium nitroprusside, acetycholine (ACH), angiotensin-II, and N(g)-nitro-L
      arginine methyl ester were assessed by venous occlusion strain gauge
      plethysmography. The endothelium-dependent increase in FBF was greater in
      response in ACH infusion after omega-3 fatty acid administration (7.9, 95%
      confidence interval [CI] 4.81 to 11.08 to 11.3, 95% CI 7.31 to 15.23 arbitrary
      units (p <0.05) compared with baseline (7.95, 95% CI 4.8 to 11.08 arbitrary
      units) and olive oil administration (7.27, 95% CI 4.66 to 9.88 arbitrary units)
      (p = NS for both). Neither omega-3 fatty acid nor olive oil altered endothelium
      independent vasodilation in response to infusion of sodium nitroprusside, nor did
      they influence vasoconstrictor responses to angiotensin-II or N(g)-nitro-L
      arginine methyl ester. Dietary omega-3 fatty acid supplementation was accompanied
      by an increase in FBF response to ACH, which represents enhanced endothelium
      dependent vasodilation in CHF. Further studies are warranted to assess the
      mechanism responsible for the beneficial actions of omega-3 fatty acids in CHF.

PMID- 16461055
TI  - Correlation of echo-Doppler optimization of atrioventricular delay in cardiac
      resynchronization therapy with invasive hemodynamics in patients with heart
      failure secondary to ischemic or idiopathic dilated cardiomyopathy.
AB  - This study investigated the optimal echocardiographic indexes to determine the
      most hemodynamically appropriate atrioventricular (AV) delay in cardiac
      resynchronization therapy (CRT) for heart failure. Doppler echocardiographic
      optimization of AV delay in CRT has not been correlated with invasive hemodynamic
      indexes. In 30 patients who underwent CRT, invasive left ventricular (LV)
      pressure measurements with a sensor-tipped pressure guidewire and Doppler
      echocardiographic examination were performed <24 hours after pacemaker
      implantation. Invasively, the optimal sensed AV delay was determined by LV
      dP/dt(max). The Doppler echocardiographic methods evaluated were the velocity
      time integral (VTI) of the transmitral flow (EA VTI), diastolic filling time (EA
      duration), the VTI of the LV outflow tract or aorta (LV VTI), and Ritter's
      formula. Biventricular pacing with optimized interventricular and AV delay
      increased LV dP/dt(max) from 777 +/- 149 to 1,010 +/- 163 dynes/s (p<0.0001). The
      optimal AV delay with the EA VTI method was concordant with LV dP/dt(max) in 29
      of 30 patients (r = 0.96), with EA duration in 20 of 30 patients (r= 0.83), with
      LV VTI in 13 patients (r = 0.54), and with Ritter's formula in none of the
      patients (r = 0.35). In conclusion, to obtain the optimal acute hemodynamic
      benefit of CRT, Doppler echocardiography is a reliable tool to optimize the AV
      delay compared with the invasive LV dP/dt(max). The measurement of the maximal
      VTI of mitral inflow is the most accurate method.

PMID- 16461056
TI  - Cardiac conduction disturbances seen after transcatheter device closure of
      muscular ventricular septal defects with the Amplatzer occluder.
AB  - This study examined the incidence of cardiac conduction abnormalities and
      ventricular arrhythmias after the transcatheter closure of muscular ventricular
      septal defects (MVSDs) using the Amplatzer device occluder. From the records of
      27 patients who underwent 33 consecutive MVSD device closures, a low incidence of
      permanent and transient cardiac conduction disturbances was observed. Heart rate
      variability was less after the closure of multiple MVSDs compared with single
      MVSDs.

PMID- 16461057
TI  - Relation of coronary hypersensitivity to serotonin in cardiac transplant
      recipients to vessel wall morphology and effect of vitamin C.
AB  - Coronary hypersensitivity to serotonin promotes platelet aggregation, entailing
      the progression of the atherosclerotic process. This abnormality is a common
      finding in cardiac transplant recipients and may be triggered by reactive oxygen
      species, which plays a main role in the inflammatory process. Hence, this study
      aimed to determine the influence of intimal hyperplasia on this abnormality and
      its reversibility after acute supplementation with the superoxide anion scavenger
      vitamin C. Therefore, intracoronary injections of serotonin (3 microg),
      bradykinin (600 ng), and nitroglycerin (isosorbide dinitrate 200 microg) were
      administered to 21 cardiac transplant recipients (1 year after transplantation)
      with normal coronary angiographic results; the serotonin injections were repeated
      after intracoronary vitamin C supplementation (40 mg/min for 14 minutes). In the
      segments in which serotonin effects were the most pronounced, the diameter
      changes were measured by quantitative angiography, and vessel wall morphology was
      studied by intravascular ultrasound (IVUS). The IVUS examination revealed
      moderate to severe intimal thickening (total area - luminal area/total area) in 9
      patients (group 1) of 25 +/- 2%, compatible with the early stage of graft
      vasculopathy. In this group, hypersensitivity to serotonin remained unchanged
      after intracoronary vitamin C supplementation, from -21 +/- 3% (percentage from
      baseline) to -25 +/- 3%, whereas in the other 12 patients with mild intimal
      thickening (9 +/- 1%; group 2), hypersensitivity to serotonin was attenuated from
      -20 +/- 5% to -4 +/- 6% (p <0.01). In contrast, the responses to bradykinin and
      isosorbide dinitrate were similar in the 2 groups. In group 1, plasma levels of
      high-sensitivity C-reactive protein and proinflammatory cytokines (interleukin-6
      and -8) were significantly enhanced. For all the patients studied, the effect of
      vitamin C on the response to serotonin was significantly correlated with the
      intimal thickening. In conclusion, at 1 year after transplantation, morphologic
      changes compatible with the early stage of the graft vasculopathy are accompanied
      by hypersensitivity to serotonin unresponsive to vitamin C, despite a relatively
      preserved endothelial function (unaltered response to bradykinin).

PMID- 16461059
TI  - Aortic wall mechanics in the Marfan syndrome assessed by transesophageal tissue
      Doppler echocardiography.
AB  - The aim of this study was to investigate the value of tissue Doppler imaging
      (TDI) using transesophageal echocardiography (TEE) in assessing the elastic
      properties of the thoracic aorta in patients with Marfan's syndrome. Aortic
      distensibility, stiffness index, and pulse-wave velocity were calculated using M
      mode data in a TEE short-axis view in 31 patients with Marfan's syndrome and 22
      normal controls. Acceleration time, maximum wall expansion velocity (Vmax), and
      wall strain were determined from TDI tracings. Indexes derived from TDI differed
      at a greater level of significance than M-mode-derived indexes in patients with
      dilated and normal aortas. Significant predictors of aortic dilation were
      systolic blood pressure, aortic stiffness index, Vmax, and strain. Decreased
      aortic strain and Vmax and increased stiffness index were predictive of aortic
      dissection (odds ratios 4.5, 3.3, and 2.2). In conclusion, the TDI assessment of
      aortic wall mechanics is complementary to standard M-mode measurements in
      discriminating normal subjects from patients with Marfan's syndrome and is
      accurate in predicting aortic dilation and dissection.

PMID- 16461058
TI  - Comparison of aspirin resistance in type 1 versus type 2 diabetes mellitus.
AB  - This study sought to determine the frequency of aspirin resistance in an
      ambulatory population of patients with type 1 diabetes mellitus (T1D) or type 2
      diabetes mellitus (T2D). Platelet aggregation was assessed during the routine
      clinical evaluation of 203 ambulatory patients with diabetes (T1D, n = 92; T2D, n
      = 111) who were recommended aspirin for primary or secondary cardiovascular
      protection. Consecutively received laboratory samples were evaluated using the
      Ultegra Rapid Platelet Function Assay-ASA. Resistance to aspirin was detected in
      18.7% of diabetic aspirin users, with similar rates in T1D (21.7%, p = 0.5) and
      T2D (16.2%, p = 0.6). Aspirin resistance was not related to age, glycohemoglobin,
      total cholesterol, or a history of cardiovascular disease. Female gender was a
      strong independent predictor of aspirin resistance in patients with T1D (p =
      0.001). Platelet aggregation was correlated with high-density lipoprotein (HDL)
      cholesterol in the entire cohort (r = 0.21, p = 0.005) and in patients with T1D
      (r = 0.32, p = 0.04) or T2D (r = 0.21, p = 0.04), such that patients with low HDL
      cholesterol levels were more likely to be aspirin sensitive. The results suggest
      that aspirin can inhibit platelet aggregation in most patients with diabetes and
      is a reasonable first-line antiplatelet agent in patients with diabetes.

PMID- 16461061
TI  - The sphygmograph in America: writing the pulse.
AB  - The sphygmograph (literally a "pulse writer") was 1 of the first "instruments of
      precision" to be used in examining the cardiovascular system. In the 1860s and
      1870s, some physiologically oriented American practitioners began using European
      sphygmographs to evaluate patients with a variety of cardiovascular and other
      disorders, study the action of drugs, assess arterial tension, and determine what
      was referred to as the "state of the circulation." Three previously unrecognized
      Americans modified existing European models or constructed original instruments
      of their own design. Two of these American "sphygmograph men" published the
      results of their novel experimental work, and the third produced a successful
      commercial model. Despite early expectations that the sphygmograph would reveal
      precise information about cardiovascular disease, the various models proved
      frustrating to use in practice. Recorded sphygmograms defied precise
      interpretation and correlation with clinical and pathologic findings. The
      sphygmograph, which faded from practice by the 1890s, helped prepare
      practitioners for more durable technologies such as the sphygmomanometer and
      electrocardiograph, which entered practice early in the 20th century. The
      sphygmograph and its American champions were overshadowed and quickly forgotten.

PMID- 16461060
TI  - A video based training program improves defibrillator inspection compliance.
AB  - Improperly maintained defibrillators are an important cause of defibrillation
      delay or failure during in-hospital cardiac arrest. This study investigated
      whether a brief training video of how to properly inspect crash carts and
      defibrillators would improve the quality and frequency of these inspections. The
      study was a before-after cohort design. Crash cart inspection logs were
      explicitly examined, and the electronic archive records of the defibrillators
      were interrogated. The compliance and quality of inspections were compared before
      and after the implementation of the training video program. The missed-inspection
      rate for defibrillators significantly improved from 8.9% to 6.9% (p= 0.037) after
      video training program implementation. The missed-inspection rate for crash
      carts, however, actually worsened from 2.7% before to 8.0% (p = 0.0001). The
      introduction of a new crash cart inspection training video program improved the
      frequency and quality of defibrillator inspections but not crash cart
      inspections. The inspection of crash carts and defibrillators is a vital hospital
      task. Because available training time for clinical personnel is limited, our 15
      minute video can be viewed on a ward computer workstation at the most convenient
      time.

PMID- 16461062
TI  - The heaviest known operatively-excised aortic valve.
AB  - A 60-year-old man whose operatively excised stenotic and regurgitant aortic valve
      weighed nearly 15 g, approximately 30 times the normal weight in an adult, is
      described. To the investigators' knowledge, this is the heaviest aortic valve
      ever encountered in a human being.

PMID- 16461063
TI  - Relation between ascending aortic pressures and outcomes in patients with
      angiographically demonstrated coronary artery disease.

PMID- 16461064
TI  - Hyperinsulinemia and not glucose level is a predisposing factor to endothelial
      dysfunction.

PMID- 16461065
TI  - Cardiac catheterization laboratory and transfer for percutaneous coronary
      intervention: available to all?

PMID- 16461066
TI  - Measuring quality in arthritis care: the Arthritis Foundation's quality indicator
      set for rheumatoid arthritis.

PMID- 16461067
TI  - Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis--setting the
      record straight.

PMID- 16461068
TI  - Measuring process of arthritis care: the Arthritis Foundation's quality indicator
      set for rheumatoid arthritis.
AB  - OBJECTIVE: To describe the scientific evidence that supports each of the explicit
      process measures in the Arthritis Foundation's Quality Indicator Set for
      Rheumatoid Arthritis. METHODS: For each of the 27 measures in the Arthritis
      Foundation's Quality Indicator set, a comprehensive literature review was
      performed for evidence that linked the process of care defined in the indicator
      with relevant clinical outcomes and to summarize practice guidelines relevant to
      the indicators. RESULTS: Over 7500 titles were identified and reviewed. For each
      of the indicators the scientific evidence to support or refute the quality
      indicator was summarized. We found direct evidence that supported a process
      outcome link for 15 of the indicators, an indirect link for 7 of the indicators,
      and no evidence to support or refute a link for 5. The processes of care
      described in the indicators for which no supporting/refuting data were found have
      been assumed to be so essential to care that clinical trails assessing their
      importance have not, and probably never will be, performed. The process of care
      described in all but 2 of the indicators is recommended in 1 or more practice
      guidelines. CONCLUSION: There are sufficient scientific evidence and expert
      consensus to support the Arthritis Foundation's Quality Indicator Set for
      Rheumatoid Arthritis, which defines a minimal standard of care that can be used
      to assess health care quality for patients with rheumatoid arthritis.

PMID- 16461070
TI  - Ischemic stroke in a postpartum patient: understanding the epidemiology,
      pathogenesis, and outcome of Moyamoya disease.
AB  - BACKGROUND: Moyamoya disease (MMD), or spontaneous occlusion of blood vessels in
      the circle of Willis, is a noninflammatory, nonatheromatous vasculopathy that
      often presents with ischemia or hemorrhage and has a tendency to affect young
      women. We discuss a case of a woman 7 days postpartum with new onset strokes,
      suspected initially to have benign angiopathy of the central nervous system
      (BACNS)/postpartum angiopathy versus primary CNS vasculitis. Cerebral angiography
      was suspicious for MMD and the patient underwent surgical revascularization.
      OBJECTIVES: To review the epidemiology, presentation, diagnosis, differential
      diagnosis, treatment, prognosis, and postpartum maternal outcomes of MMD.
      METHODS: The authors reviewed the English-language literature published between
      1996 and 2004 using Medline databases. Additional articles were obtained from
      references described in literature obtained by the primary search. RESULTS: MMD
      is characterized by severe bilateral stenosis of the distal internal carotid
      arteries and their first branches, with prominent collateralization.
      Autoantibodies relating to endothelial cell dysfunction have been studied as
      possible pathogenetic mechanisms. The gold standard for diagnosing MMD is digital
      subtraction contrast angiography (DSA). MMD-related findings on imaging studies
      may, at times, be mistaken for those of vasculitis. A surgical approach may need
      to be considered. Despite treatment, the overall prognosis of MMD is worse in
      adults compared with children. CONCLUSION: Awareness of the specific features of
      MMD is crucial for clinical decision-making to avoid unnecessary exposure to
      aggressive immunosuppressive therapy. It is important for rheumatologists to
      consider MMD in the differential diagnosis of suspected CNS vasculitis.

PMID- 16461069
TI  - Description of 12 cases of nephrogenic fibrosing dermopathy and review of the
      literature.
AB  - OBJECTIVES: To review the clinical and laboratory features of 12 cases of
      nephrogenic fibrosing dermopathy (NFD) studied at our institution and of 70
      previously described cases in the literature. METHODS: Clinical evaluation and
      laboratory studies of 12 patients with NFD associated with chronic hemodialysis
      or peritoneal dialysis for end-stage renal disease and a review of 23 previous
      publications describing 70 patients with this disease. RESULTS: Eleven patients
      undergoing chronic hemodialysis and 1 patient undergoing chronic peritoneal
      dialysis for end-stage renal failure developed a severe and progressive cutaneous
      fibrotic process with woody induration of legs, thighs, hands, and forearms, and
      severe loss of motion and flexion contractures in multiple joints. Several
      patients displayed systemic involvement including fibrosis of muscles,
      myocardium, and lungs and marked elevations of the erythrocyte sedimentation rate
      and/or C-reactive protein. Three patients died within 2 years of symptom onset. A
      review of previously published reports of this disorder confirmed the presence of
      systemic involvement and a poor prognosis with a high mortality rate.
      CONCLUSIONS: NFD is a severe and usually progressive systemic fibrotic disease
      affecting the dermis, subcutaneous fascia, and striated muscles. It also appears
      that the disease can cause fibrosis of lungs, myocardium, and other organs.

PMID- 16461071
TI  - Lupus-associated pancreatitis.
AB  - OBJECTIVES: Involvement of the pancreas in systemic lupus erythematosus is rare.
      The purpose of this article is to provide a detailed review of lupus-associated
      pancreatitis. METHODS: We describe 3 patients with lupus-associated pancreatitis
      and review the English literature of the last 30 years, including the
      demographic, clinical, therapeutic, and prognostic aspects of this disorder.
      RESULTS: There were detailed descriptions of 77 patients, 88% were females.
      Median age was 27 years. In 44% of the patients pancreatitis developed within 1
      year of the diagnosis of lupus, and 84% had active lupus at the time of
      pancreatitis. Abdominal pain was the most frequent pancreatitis-related symptom
      (88%), followed by nausea or vomiting (67%). In 97% the diagnosis of pancreatitis
      was based on laboratory evidence of elevated serum amylase or lipase. Abdominal
      computerized tomography and ultrasonography did not show signs of pancreatic
      involvement in 24 and 45%, respectively. The mortality rate was 27%; active lupus
      and some biochemical abnormalities were significantly associated with increased
      mortality. Treatment with corticosteroids or azathioprine was not associated with
      increased mortality. On the contrary, mortality was decreased in patients who
      were treated with these agents after the onset of pancreatitis (20% mortality,
      compared with 61% among those who were not treated with steroids for their
      pancreatitis, P = 0.005). CONCLUSIONS: Pancreatitis should be suspected in any
      SLE patient with abdominal pain. Mortality rate is related to both active lupus
      and some biochemical markers. In most cases, the onset of pancreatitis appears
      unrelated to previous treatment with steroids or azathioprine. Moreover,
      treatment with these medications improves prognosis.

PMID- 16461072
TI  - Antiphospholipid syndrome in patients with retinal venous occlusion.
AB  - INTRODUCTION: We conducted a prospective study to determine the prevalence and
      the prognosis of antiphospholipid syndrome (APS) in patients with retinal venous
      occlusion (RVO). PATIENTS: Consecutive patients presenting with retinal vein
      occlusion were screened for vascular risk factors (diabetes mellitus,
      hypertension, hyperlipidemia) and for antiphospholipid antibodies (aPL):
      anticardiolipin (aCL), anti-beta2-glycoprotein I, and lupus anticoagulant.
      Patients with a serum sample positive for aPL returned at least 6 weeks later for
      a new screening to determine the prevalence of antiphospholipid syndrome. All
      patients were followed to determine the outcome. RESULTS: Sixty-eight patients
      presented with RVO, 16 had vascular risk factors for RVO. After two screenings
      for aPL, nine cases of antiphospholipid syndrome associated with RVO were
      diagnosed (13.2%). Eight patients were over age 50 years and none had a previous
      thrombotic event before RVO. All patients were treated with aspirin (160 mg/day).
      With a mean follow-up of 26.1+/-8.2 months (range, 16-36 months), there were no
      recurrences. CONCLUSION: Retinal venous occlusion is multifactorial in origin. In
      patients aged 50 years and older, without previous thrombotic event, aPL might
      not be predictive of recurrences and treatment with aspirin might be sufficient.
      In such patients, the routine screening for aPL does not appear warranted, but a
      randomized study should be conducted to really ascertain the pathogenic role of
      aPL and the most appropriate treatment in RVO.

PMID- 16461073
TI  - Cytoplasmic free calcium mobilization in platelets, expression of P-selectin,
      phosphatidylserine, and microparticle formation, measured by whole blood flow
      cytometry, in hypertensive patients. Effect of doxazosin GITS.
AB  - The effects of doxazosin on expression of CD62 (P-selectin) and
      phosphatidylserine on platelet membrane and platelet calcium flux were studied in
      50 uncomplicated essential hypertensive patients (World Health Organization
      stages 1-2) and 80 normotensive control subjects, matched for age, sex, and
      cardiovascular risk factors. Hypertensive patients showed greater in vivo
      platelet activation at baseline than control patients (percentage of CD62
      positive platelets, 4.1+/-2.2% versus 2.4+/-1.5%, p<0.001; percentage of
      phosphatidylserine-positive platelets, 0.8+/-0.5% versus 0.5+/-0.3%, p<0.001).
      Increased platelet activation was associated with significant changes in the
      mobilization of free intraplatelet calcium, evaluated by a whole blood flow
      cytometric kinetic method. With this method, an arbitrary Ca(2+) mobilization
      index was defined as the ratio of cytoplasmic free calcium before activation with
      thrombin to the slope of the calcium removal rate following the action of the
      agonist. This index was significantly higher in untreated hypertensive patients
      than in normotensive controls (0.12+/-0.06 versus 0.05+/-0.08, p<0.001).
      Treatment of hypertensive patients with doxazosin gastrointestinal therapeutic
      system (4 mg/day as a single dose) for 2 months normalized both platelet
      activation and Ca(2+) mobilization. Changes in the expression of CD62 and
      phosphatidylserine in the platelet membrane after treatment with doxazosin
      gastrointestinal therapeutic system may be related to normalization of the
      kinetics of cytoplasmic free Ca(2+). Normalization of platelet activation may
      represent an additional beneficial effect to the known antihypertensive action of
      doxazosin gastrointestinal therapeutic system.

PMID- 16461074
TI  - Evaluation and management of malfunctioning sacral neuromodulator.
AB  - OBJECTIVES: To describe a strategy for revising the malfunctioning InterStim
      device and to provide an algorithm for evaluation and management. METHODS: We
      retrospectively reviewed 82 patients who had undergone InterStim placement. Ten
      patients (eight women and two men) experienced complications and subsequently
      underwent revision of their device between October 2001 and October 2003. Five
      patients had originally received a permanent implant after a successful
      percutaneous test stimulation trial, and five had undergone a test stimulation
      using the tined lead. Indications for revision included gradual onset of
      recurrent voiding dysfunction (n = 2), lead migration (n = 5), generator
      malfunction (n = 1), generator site pain and infection (n = 1), and
      genital/rectal pain with stimulation (sensory discomfort; n = 1). RESULTS: Of the
      10 patients who underwent revision, 7 experienced complete resolution of their
      problem. Eight patients had lead site changes and two had generator replacements.
      No intraoperative or postoperative complications occurred in the revision cases.
      CONCLUSIONS: In our experience, 70% of patients who undergo revision of the
      malfunctioning InterStim can expect success. In this study, no difference in
      success appeared to be related to the original cause of malfunction. In the
      management of malfunctioning sacral neuromodulators, we recommend an attempt at
      revision before permanent explantation.

PMID- 16461075
TI  - Partial nephrectomy and radical nephrectomy offer similar cancer outcomes in
      renal cortical tumors 4 cm or larger.
AB  - OBJECTIVES: To determine whether the type of surgery (partial nephrectomy [PN]
      versus radical nephrectomy [RN]) has any effect on cancer outcome for renal
      cortical tumors 4 cm or larger. PN outcomes for large renal cortical tumors have
      been shown to be worse than outcomes for smaller tumors, but the upper limit of
      tumor diameter amenable to PN remains controversial. METHODS: We identified 33
      patients from the Columbia University Comprehensive Urologic Oncology Database
      who underwent PN between 1988 and 2004 for renal cortical tumors 4 cm or larger.
      Each was matched with 2 patients undergoing RN on the basis of the tumor
      diameter. A survival analysis was conducted using the Kaplan-Meier method, and
      any differences between the two groups were compared using the log-rank test. The
      Cox regression model was used to determine which variables affected survival.
      RESULTS: The estimated 5-year recurrence-free survival rate was 93.5% for the PN
      group and 83.3% for the RN group (P = 0.471). The estimated 5-year disease
      specific survival rate was 96.2% for the PN group and 97.8% for the RN group (P =
      0.893). Only tumor diameter had an impact on recurrence-free survival in the
      univariate (P = 0.005) and multivariate (P = 0.008) Cox regression models.
      Surgical technique had no impact on disease recurrence. CONCLUSIONS: The results
      of our study have shown that cancer outcomes after PN do not differ from outcomes
      after RN for tumors of 4 cm or greater in diameter. The upper limit of 4 cm
      appears to have been determined arbitrarily. It is no longer advisable to
      restrict PN to patients with tumors smaller than 4 cm in diameter.

PMID- 16461076
TI  - Radiation exposure during standing voiding cystourethrography in women.
AB  - OBJECTIVES: To calculate the total radiation exposure and effective organ doses
      from standard protocol voiding cystourethrography (VCUG). METHODS: A prospective
      series of consecutive, non-neurogenic women underwent a standardized VCUG
      protocol by the same technologist using a Siemens Sireskop Fluorospot
      radiographic/fluoroscopic unit. Only studies that followed the protocol were
      included. The effective dose was calculated using a commercially available dose
      modeling program (PCXMC, version 1.5) for risk assessment. RESULTS: A total of
      119 studies in 118 women (mean age 60 +/- 13 years, range 30 to 93) were
      included. Only 15 patients (13%) were premenopausal with in situ reproductive
      organs. The mean number of images and fluoroscopic time per study was 12.8 +/-
      1.4 (lateral images 7.5 +/- 1.3) and 35.8 +/- 11.2 seconds, respectively. The
      mean effective dose for a single VCUG study was calculated to be 4.3 mSv, of
      which 26% was from fluoroscopy (1.1 mSv). The dose to the gonads accounted for
      50% of the total effective organ dose. Using whole population radiologic risk
      factors, the total risk detriment, cancer and hereditary, was about 3 per 10,000
      patients or a 99.997% chance of no detriment incurred from the study. The genetic
      and malignant risks were reduced in this cohort of patients, who were older, with
      most (87%) having no reproductive potential. CONCLUSIONS: Using a standard
      protocol for adult women, a VCUG study is associated with an acceptable radiation
      risk.

PMID- 16461077
TI  - Multicenter phase III trial studying trospium chloride in patients with
      overactive bladder.
AB  - OBJECTIVES: To study the efficacy and safety of trospium chloride in treating
      overactive bladder. Trospium chloride is an anticholinergic agent with
      predominantly peripheral nonselective antimuscarinic activity and thus has
      potential therapeutic value in treating patients with overactive bladder.
      METHODS: Patients with overactive bladder were randomized on a 1:1 basis to
      either placebo or trospium chloride 20 mg twice daily in this 12-week,
      multicenter, parallel, double-blind, placebo-controlled study. The primary
      endpoint was the change in the average number of toilet voids per 24 hours. The
      secondary efficacy variables were changes in the average void urgency severity,
      volume per toilet void, urge frequency, number of daily urge urinary incontinence
      episodes, and daytime sleepiness. RESULTS: A total of 658 patients were
      randomized at 52 sites. Trospium chloride significantly decreased the average
      number of daily toilet voids, average urgency severity, urge frequency, and urge
      urinary incontinence episodes and increased the average volume per void at weeks
      1, 4, and 12. All effects occurred by the end of week 1 and all improved and were
      sustained throughout the 12-week study. Adverse events included dry mouth and
      constipation. CONCLUSIONS: Trospium chloride had significant and sustained
      effectiveness beginning at the end of week 1 and continuing through 12 weeks of
      treatment. Trospium chloride was also safe and generally well tolerated.

PMID- 16461078
TI  - True prevalence of urinary incontinence among female nursing home residents.
AB  - OBJECTIVES: Urinary incontinence is a significant problem in nursing home
      residents in the United States. Estimates of its prevalence have often been based
      on data from medical records obtained at nursing home admission. To measure the
      sensitivity of this method of defining the prevalence of urinary incontinence
      among female nursing home residents, we examined data from a clinical survey.
      METHODS: We analyzed data from the National Nursing Home Survey, which collected
      information from nursing homes for each resident concerning admission diagnoses,
      presence of an indwelling Foley catheter or ostomy, need for assistance from
      equipment or personnel in using the toilet, and difficulty controlling urination.
      RESULTS: Residents' medical records revealed a very low rate of admission
      diagnoses of incontinence. However, clinical queries revealed a high prevalence
      of bladder dysfunction. More than one half of all female nursing home residents
      were reported to have "difficulty controlling urination," and more than one half
      needed assistance in using the toilet. CONCLUSIONS: Although only 1% to 2% of
      nursing home residents have a diagnosis of urinary incontinence, the true
      prevalence of bladder dysfunction in this group is much greater. The sharp
      divergence of National Nursing Home Survey data from published studies on the
      prevalence of incontinence in nursing homes highlights the limitations of using
      administrative data to study the epidemiology of bladder dysfunction.

PMID- 16461079
TI  - Urine prothymosin-alpha as novel tumor marker for detection and follow-up of
      bladder cancer.
AB  - OBJECTIVES: To establish the normal range of urine prothymosin-alpha in humans
      and to investigate its role as a specific tumor marker for the detection and
      follow-up of transitional cell carcinoma of the urinary bladder before and after
      curative treatment. METHODS: Urine samples were obtained from 151 healthy
      volunteers, 60 patients with urinary tract infection, 238 patients with bladder
      transitional cell carcinoma (96 with tumor and 142 tumor free), and 22 patients
      with non-transitional cell carcinoma tumors. The urine prothymosin-alpha levels
      were quantified by enzyme-linked immunosorbent assay and then appropriately
      analyzed and compared among the different study groups. RESULTS: The mean value
      of urine prothymosin-alpha in healthy volunteers was 0.68 +/- 0.13 ng/mL.
      Regardless of the presence of urinary tract infection, the urine prothymosin
      alpha level in patients with newly diagnosed, as yet untreated, bladder cancer
      was significantly greater than that in those who were tumor free after curative
      treatment (P = 0.050 and P = 0.026 for the presence and absence of urinary tract
      infection, respectively). At follow-up, the urine prothymosin-alpha level was
      constantly elevated when residual or recurrent tumor was present after treatment.
      Although the urine prothymosin-alpha level in patients with non-transitional cell
      carcinoma tumors was not significantly different from that of healthy volunteers,
      it was definitely lower than the level in patients with bladder tumors (P =
      0.003). CONCLUSIONS: Our findings have revealed that urine prothymosin-alpha has
      the potential of being a useful tumor marker for the detection and follow-up of
      bladder cancer.

PMID- 16461081
TI  - Predictives regarding outcome after transurethral resection for prostatic adenoma
      associated with detrusor underactivity.
AB  - OBJECTIVES: To elucidate the predictive factors regarding the treatment outcomes
      after transurethral resection of the prostate for symptomatic benign prostatic
      enlargement with detrusor underactivity. METHODS: A retrospective study was
      conducted in 190 patients with detrusor underactivity of 1397 men who had
      undergone transurethral resection of the prostate. All patients had completed the
      International Prostate Symptom Score and quality-of-life (QOL) questionnaires and
      had undergone a full urodynamic analysis before surgery. The outcomes were
      assessed at 3 and 12 months postoperatively using the International Prostate
      Symptom Score, QOL score, and peak urinary flow rate. The association between the
      baseline variables and improvement in the outcome variables was analyzed
      statistically. RESULTS: Preoperative urodynamic abnormalities included bladder
      outlet obstruction in 58.9% and detrusor overactivity (DO) in 32.1%. Multivariate
      analysis suggested that the initial level of storage symptoms, as well as the QOL
      score, were predictive of an improvement in the QOL. Postoperative improvement in
      symptoms and QOL was consistently influenced by the presence of DO before
      surgery. The baseline degree of bladder outlet obstruction, as well as patient
      age, consistently influenced the improvement in the peak urinary flow rate.
      CONCLUSIONS: In selected patients with benign prostatic enlargement associated
      with detrusor underactivity, greater baseline storage symptom scores and the
      presence of DO were negative predictive factors for QOL improvement. Baseline DO
      was also predictive of poorer improvement in the subjective symptoms after
      transurethral resection of the prostate. A greater degree of baseline bladder
      outlet obstruction positively predicted for postoperative peak urinary flow rate
      improvement, and patient age predicted negatively for it.

PMID- 16461080
TI  - Growth factor, cytokine, and vitamin D receptor polymorphisms and risk of benign
      prostatic hyperplasia in a community-based cohort of men.
AB  - OBJECTIVES: To investigate the associations between benign prostatic hyperplasia
      (BPH) and polymorphisms in genes that encode growth factors, cytokines, and
      vitamin D and their receptors. METHODS: A total of 510 white men (median age 60
      years) randomly selected from the Olmsted County, Minnesota community
      participated in a study of BPH from 1990 to 2000. Biennial measurements were made
      to assess the International Prostate Symptom Score, peak urinary flow rate, and
      prostate volume. Genotyping of genes that encode transforming growth factor,
      interleukin-10, tumor necrosis factor, and vitamin D receptor, among others, was
      performed. RESULTS: The CC genotype of the transforming growth factor-beta 1 gene
      was inversely associated with treatment for BPH (hazard ratio [HR] 0.38, 95%
      confidence interval [CI] 0.15 to 0.98). The presence of at least one allele with
      17 or more CA repeats of the epidermal growth factor receptor gene was positively
      associated with an International Prostate Symptom Score greater than 7 (HR 1.32,
      95% CI 1.01 to 1.73). The AA genotype of tumor necrosis factor-alpha was
      inversely associated with peak urinary flow rate (HR 0.33, 95% CI 0.12 to 0.90).
      For the vitamin D receptor gene, positive associations were found between
      prostate volume and the CC genotype of the T_C (Taq 1) polymorphism (HR 1.39, 95%
      CI 1.0 to 1.92) and the AA genotype of the G_A (Bsm 1) polymorphism (HR 1.36, 95%
      CI 1.06 to 1.74). CONCLUSIONS: These findings suggest that transforming growth
      factor-beta 1, tumor necrosis factor-alpha, epidermal growth factor receptor, and
      vitamin D receptor polymorphisms may be involved in the pathogenesis of BPH.

PMID- 16461082
TI  - Complexed PSA improves prostate cancer detection: results from a multicenter
      Japanese clinical trial.
AB  - OBJECTIVES: To compare the distribution of total and complexed prostate-specific
      antigen (cPSA) in men with and without prostate cancer with another studied
      population and to ascertain whether cPSA could enhance the detection of prostate
      cancer in Japanese men. METHODS: A total of 760 men whose serum total PSA (tPSA)
      values ranged from 1.0 to 100 ng/mL were enrolled. Serum samples for tPSA and
      cPSA (ADVIA Centaur) were obtained in all cases. The area under the curve was
      calculated for comparison of the tPSA and cPSA values. We calculated the number
      of cancers missed and false-positive results at various cutoff values of cPSA
      compared with the conventional tPSA threshold of 4.0 ng/mL. RESULTS: Prostate
      cancer was detected in 268 (35.3%) of 760 patients. cPSA was greater than 8.3
      ng/mL (equivalent to 10.0 ng/mL tPSA) in 46.6% of the men with cancer. The area
      under the curve for cPSA (0.741) was significantly better than that for tPSA
      (0.721, P <0.001). At a sensitivity of 85% to 95%, significant differences were
      found in the corresponding specificity between tPSA and cPSA. cPSA at a 3.0-ng/mL
      threshold detected an identical number of cancers as a tPSA cutoff of 4.0 ng/mL;
      however, it decreased the false-positive results by 28 cases. CONCLUSIONS: To our
      knowledge, this is the first report of the distribution of cPSA in Japanese men
      using a urologic referral population. cPSA can be an alternative to tPSA as the
      first screening test. A substantial number of men in Japan with prostate cancer
      are currently diagnosed with a tPSA value greater than 10.0 ng/mL.

PMID- 16461083
TI  - Detection rate of prostate cancer on biopsy according to serum prostate-specific
      antigen in Korean men: a multicenter study.
AB  - OBJECTIVES: To evaluate the detection rate of prostate cancer on biopsy according
      to the serum prostate-specific antigen (PSA) level in Korean men and compare the
      detection rate with those of Japanese and American men in other studies. METHODS:
      We retrospectively analyzed 2422 Korean men who had undergone prostate biopsy at
      12 medical centers from 1993 to 2002. In the case of a PSA level greater than 4.0
      ng/mL or abnormal digital rectal examination findings, prostate biopsy was
      performed. RESULTS: Of the 2422 men, 962 (39.7%) were diagnosed with prostate
      cancer. With PSA levels between 4.0 and 10.0 ng/mL, the detection rate of
      prostate cancer was 15.9%. This rate was similar to that of Japanese men (15.8%),
      but lower than that of American men (25%). In the cases with a PSA level greater
      than 10.0 ng/mL, the detection rate for Korean and Japanese men was 59.5%, and
      was also lower than the 67% rate for American men. When serum PSA levels were
      divided into five subgroups (less than 4.0, 4.0 to 10.0, 10.0 to 20.0, 20.0 to
      100.0, and greater than 100.0 ng/mL), the detection rate of prostate cancer was
      12.4%, 15.9%, 34.1%, 66.2%, and 93.8%, respectively. CONCLUSIONS: In Korean men,
      the detection rate of prostate cancer on biopsy according to serum PSA level
      appears to be comparable to that for Japanese men and lower than that for
      American men.

PMID- 16461084
TI  - Percentage of positive biopsies associated with freedom from biochemical
      recurrence after low-dose-rate prostate brachytherapy alone for clinically
      localized prostate cancer.
AB  - OBJECTIVES: To examine the relationship between the percentage of positive
      biopsies (PPBs) and freedom from biochemical recurrence (FFBR) in men treated
      with low-dose-rate prostate brachytherapy (LDRPB) alone. The PPBs has been
      associated with FFBR in men treated with radical prostatectomy and external beam
      radiotherapy for prostate cancer. METHODS: This report concerns 108 men treated
      with LDRPB alone between November 1997 and December 1999. All patients had
      clinically localized prostate cancer confirmed by biopsy. All men were treated
      with iodine-125 to 144 Gy. FFBR was estimated using the product-limit method.
      Putative covariates for FFBR, including T stage, Gleason score, pretreatment
      prostate-specific antigen level, minimal dose received by 90% of the target
      volume, and PPBs, were examined using the proportional hazards regression model.
      RESULTS: The median follow-up was 61 months. Of the 108 men, 13 developed
      evidence of biochemical relapse at a median of 25 months. The 5-year estimate of
      FFBR was 87% (95% confidence interval 81% to 93%) for the entire cohort. On
      univariate analysis, prostate-specific antigen, T stage, minimal dose received by
      90% of the target volume, and PPBs were associated with FFBR. In the multivariate
      model, the PPBs was the only variable that predicted for FFBR (P = 0.002). The 5
      year estimate of FFBR was 95% for patients with less than 50% PPB disease versus
      63% in patients with more than 50% PPB disease (P < 0.0001). CONCLUSIONS: The
      PPBs is an important independent predictor of FFBR after LDRPB alone. The FFBR
      after LDRPB in the group of patients with more than 50% PPBs was poor.

PMID- 16461085
TI  - Intraoperative blood loss and transfusion requirements for robotic-assisted
      radical prostatectomy versus radical retropubic prostatectomy.
AB  - OBJECTIVES: To compare intraoperative blood loss, perioperative hematocrit, and
      transfusion requirements in patients undergoing radical retropubic prostatectomy
      (RRP) versus robotic-assisted laparoscopic prostatectomy (RALP) by a single
      surgeon. METHODS: During a 14-month period, 279 patients with localized carcinoma
      of the prostate were prospectively enrolled in this comparative study. The
      decision of which surgical approach to use was by patient choice. Of the 279
      patients, 176 underwent RALP and 103 underwent RRP. The serum hematocrit was
      obtained preoperatively and 24 hours postoperatively in all patients. The
      intraoperative blood loss was recorded, and transfusion requirements were noted.
      RESULTS: Patients in the RALP group had significantly less intraoperative blood
      loss compared with the RRP group (mean 191 mL versus 664 mL, P < 0.001).
      Additionally, the difference in the discharge hematocrit (36.8% versus 32.8%, P <
      0.001) and the mean perioperative change in hematocrit (8.0% decrease versus
      10.7% decrease, P < 0.001) were significant between the RALP and RRP groups,
      respectively. Three patients in the RRP group (2.9%) and one in the RALP group
      (0.5%) required transfusion of blood products (P = 0.14). CONCLUSIONS: The
      results of this study have shown that RALP is associated with less intraoperative
      bleeding than RRP, and patients undergoing RALP have a greater serum hematocrit
      at hospital discharge. The lack of a statistically significant difference in
      blood transfusion was partially attributable to the low transfusion rate in both
      groups in this series.

PMID- 16461086
TI  - Robotic laparoscopic radical prostatectomy: setup and procedural techniques after
      150 cases.
AB  - OBJECTIVES: To report our current methods of patient positioning, establishing
      the pneumoperitoneum, port placement, and helpful maneuvers during the procedure
      that have been refined over the course of our initial experience with robotic
      laparoscopic radical prostatectomy (RLRP). RLRP is gaining popularity as a
      minimally invasive technique for treating patients with organ-confined prostate
      cancer. Because this is a new procedure, strategies to optimize the surgical
      technique are constantly evolving. METHODS: Two genitourinary surgeons
      experienced in open surgery with no laparoscopic experience began performing RLRP
      in December 2003 after appropriate training and mentoring. During the course of
      the ensuing 150 cases, new techniques were developed in an attempt to simplify
      the operation and improve its outcome. RESULTS: We documented and illustrated
      techniques for patient positioning, safe and rapid placement of the initial
      camera trocar, use of the third working arm of the da Vinci Surgical System,
      trocar positioning, and prostatic retraction to assist with posterior dissection.
      CONCLUSIONS: We have described setup techniques and principles we developed
      during our experience with the da Vinci robotic system. These points of technique
      may be helpful for simplifying a procedure that is still in evolution.

PMID- 16461087
TI  - Does year of radical prostatectomy independently predict outcome in prostate
      cancer?
AB  - OBJECTIVES: To examine how the biochemical outcomes after radical prostatectomy
      (RP) have changed in the prostate-specific antigen (PSA) era when controlling for
      the effects of other prognostic variables. Since the beginning of the PSA era,
      the presentation, treatment, and therapeutic outcomes of prostate cancer have
      evolved. METHODS: We reviewed the Columbia University Comprehensive Urologic
      Oncology Database and identified 1319 patients who had undergone RP without
      adjuvant therapy, performed by three surgeons, between 1988 and 2003 (minimal
      follow-up of 12 months). Univariate Cox proportional hazards models were used to
      determine which variables affect the hazard of biochemical failure (BCF), defined
      as a PSA level of 0.2 ng/mL or greater on at least two occasions, after RP.
      Multivariate analysis, controlling for the effects of other prognostic variables,
      was used to determine the effect that the year of surgery had on hazard of BCF.
      RESULTS: Univariate analysis confirmed the importance of the year of surgery,
      preoperative PSA level, pathologic stage, Gleason sum, and surgical margin status
      in estimating the hazard of BCF (P <0.001). Age at surgery did not have a
      statistically significant effect. A multivariate Cox model showed that the year
      of surgery had a highly significant impact on the hazard of BCF even when
      controlling for PSA, stage, Gleason sum, and surgical margin status. CONCLUSIONS:
      Patients undergoing RP in more recent years are at significantly less risk of BCF
      compared with patients who underwent surgery earlier in the PSA era, even when
      controlling for the effects of other prognostic variables. The factors that
      account for this change in outcomes over time have yet to be identified.

PMID- 16461088
TI  - Cancer progression after anterograde radical prostatectomy for pathologic Gleason
      score 8 to 10 and influence of concomitant variables.
AB  - OBJECTIVES: To evaluate the outcome in patients with clinically localized
      prostate cancer and pathologic Gleason score 8 to 10 disease treated by
      anterograde radical prostatectomy, either alone for node-negative disease or with
      early hormonal therapy for node-positive disease, and to characterize the
      prognostic significance of other pathologic variables. METHODS: A total of 729
      patients underwent radical prostatectomy for clinically localized prostate cancer
      between 1989 and 2003. We identified 116 patients (15.9%) with specimen Gleason
      score 8 or greater. The mean follow-up was 48 months (range 6 to 145). RESULTS:
      The 5-year biochemical-free survival rate for those with pT2, pT3a, and pT3b
      diseases was 100%, 65.1%, and 10.5%, respectively (P < or =0.05). The 5-year
      biochemical-free survival rate for those with specimen Gleason score 8 and 9 was
      72.1% and 38.2%, respectively (P < or =0.05). The incidence of positive surgical
      margins was 14.6% and led to a high pT3a specimen-confined detection rate. The
      preoperative prostate-specific antigen level, primary Gleason pattern, and
      surgical margin status had no statistically significant impact on biochemical
      recurrence-free survival. The multivariate Cox model showed seminal vesicle
      invasion to be the only independent prognostic factor. The 3 and 5-year
      progression-free survival rate of the 45 node-positive patients was 72.6% and
      60.5%, respectively. CONCLUSIONS: Our findings emphasize the need for early
      diagnosis, which can make this disease curable by radical prostatectomy alone,
      and show that poorly differentiated prostate cancer that has invaded the capsule
      can be cured by surgery. Biochemical recurrence represented a common event in
      pT3b and Gleason score 9 disease, suggesting a possible role for early adjuvant
      treatment.

PMID- 16461089
TI  - Role of prostate biopsy schemes in accurate prediction of Gleason scores.
AB  - OBJECTIVES: To determine whether improved prostate sampling by the extended
      biopsy scheme also improves the accuracy of the biopsy Gleason score (bGS).
      Because most prostate cancer cases are now detected at an early stage with a low
      prostate-specific antigen level, the bGS may be the most important factor in
      therapeutic decision-making. Sextant biopsy schemes had poor correlation with
      prostatectomy Gleason scores. Extended prostate biopsies have replaced the
      sextant scheme because of the former's greater cancer detection rate. METHODS: We
      identified 426 patients whose biopsy and prostatectomy specimens were reviewed at
      our center. To minimize the effect of stage migration, all patients before 1997
      were excluded. Of the 426 included patients, 221 men had undergone sextant biopsy
      and 205 men extended biopsy before prostatectomy. The rate of grading concordance
      and the effect of different variables on the concordance rate was determined.
      RESULTS: The overall accuracy of the extended and sextant schemes was 68% and 48%
      (P <0.001), respectively. Upgrading of the bGS was significantly less likely with
      the extended scheme (17% versus 41%, P <0.001). The sextant biopsy was more
      likely to be upgraded for a bGS of 6 or less (44% versus 25%, P <0.002) and a bGS
      of 7 (14% versus 3%, P <0.02). On multivariate analysis, the biopsy scheme was
      the only independent predictor of accurate Gleason scoring (P <0.001) and age,
      prostate-specific antigen level, digital rectal examination findings, prostate
      size, clinical stage, and number of positive cores were not. CONCLUSIONS: The use
      of an extended prostate biopsy scheme significantly improves the correlation
      between the bGS and prostatectomy Gleason score and reduces the risk of upgrading
      to a worse Gleason group at prostatectomy.

PMID- 16461090
TI  - Ham's F-10 medium and Ham's F-10 medium plus vitamin E have protective effect
      against oxidative stress in human semen.
AB  - OBJECTIVES: To investigate possible protective effects of vitamin E and Ham's F
      10 medium (HF-10) on lipid peroxidation, apoptosis, motility, and vitality of
      spermatozoa. METHODS: Normozoospermic semen samples were obtained from 35
      volunteers. Normal saline solution, HF-10 only, or HF-10 with vitamin E were
      added to split semen samples (control, group 1, and group 2, respectively). Sperm
      motility and vitality were evaluated at the end of 1, 2, and 24 hours. Superoxide
      dismutase, catalase, and malondialdehyde levels were assessed at the end of the
      first hour. Flow cytometric DNA analysis was performed at the end of 24 hours.
      RESULTS: Superoxide dismutase, sperm motility, and vitality were not different
      among the groups. The catalase values decreased in group 1, but not in group 2.
      Malondialdehyde values in supernatants decreased in group 2 and apoptosis of
      spermatozoa decreased in groups 1 and 2. CONCLUSIONS: Our data suggest that
      vitamin E and HF-10 protect against the reactive oxygen species-mediated damage
      on spermatozoa.

PMID- 16461092
TI  - Ungated extracorporeal shock wave lithotripsy in children: an initial series.
AB  - OBJECTIVES: Ungated extracorporeal shock wave lithotripsy (ESWL) is associated
      with cardiac arrhythmias in adults. However, the incidence of arrhythmias in
      children undergoing ungated ESWL has not been established. Therefore, we report
      on the safety and efficacy of ungated ESWL of renal calculi in children. METHODS:
      We evaluated all patients younger than 18 years of age who were undergoing
      ungated ESWL of renal calculi. All patients were monitored for arrhythmias, along
      with other standard monitoring, by the anesthesiologist. RESULTS: Eight
      consecutive children (three boys and five girls) between 3.5 and 17 years of age
      (median 13.5) underwent 10 ESWL procedures for renal calculi. Of the 10 stones, 9
      were located in the left kidney and 1 was located in the right kidney. The stone
      size ranged from 5 to 19 mm. Six patients underwent 3000 shocks and 2 patients
      underwent 800 and 2200 shocks. All patients underwent lithotripsy with a gradual
      incremental energy increase from 17 to 24 kV, except for 1 child (maximum of 18
      kV) because of the patient's age (3.5 years). No patient had cardiac arrhythmias
      or other intraoperative complications. No patient required conversion to gated
      ESWL. The overall stone-free rate was 90.0% as determined by abdominal
      radiography and renal/bladder ultrasonography. CONCLUSIONS: The results of this
      initial series suggest that ungated ESWL is safe and efficacious in patients
      younger than 18 years of age. Additional studies are warranted to evaluate
      further the use of ungated ESWL in the pediatric population.

PMID- 16461091
TI  - Comparison of efficacy of sildenafil-only, sildenafil plus topical EMLA cream,
      and topical EMLA-cream-only in treatment of premature ejaculation.
AB  - OBJECTIVES: To compare the efficacy of sildenafil (Viagra) only, sildenafil plus
      topical anesthetic cream (EMLA), and topical EMLA-cream-only to that of placebo
      in treating premature ejaculation. METHODS: A total of 84 patients were enrolled
      in this study. The duration of premature ejaculation in the patients ranged from
      9 to 60 months (mean 32.5 +/- 14.6). Patients were randomized into four groups.
      Group 1 consisted of 20 patients who took placebo for 2 months. Groups 2 and 3
      consisted of 20 and 22 patients, respectively, and they received 50 mg sildenafil
      45 minutes before coitus for 2 months. In addition, patients in group 3 applied
      topical EMLA cream to the glans penis 15 minutes before coitus. The 22 patients
      in group 4 used topical EMLA-cream-only. After at least eight sexual attempts,
      the patients' clinical responses were assessed using the patient self-description
      method. Effectiveness was described as improvement plus cure. RESULTS: The
      effectiveness was 40% in group 1, 55% in group 2, 86.4% in group 3, and 77.3% in
      group 4. Of the groups, a significant difference was found in the effectiveness
      of the treatments (Pearson chi-square= 0.00). No significant difference was found
      between groups 1 and 2 (P = 0.26). Efficacy was more successful in groups 3 and 4
      than in the others (P = 0.00). The difference between groups 3 and 4 was not
      significant (Pearson chi-square = 0.42). CONCLUSIONS: Sildenafil-only was not
      superior to placebo or combination treatment. Topical EMLA-cream-only had equal
      effectiveness to that of sildenafil plus topical EMLA treatment. The use of
      topical EMLA-cream-only seems to be an effective treatment of premature
      ejaculation.

PMID- 16461093
TI  - Primary repair of bladder exstrophy followed by clean intermittent
      catheterization: outcome of 15 years' experience.
AB  - OBJECTIVES: To determine the continence and spontaneous voiding rate after
      neonatal reconstruction of bladder exstrophy without formal bladder neck
      reconstruction in patients undergoing primary reconstruction and treated with
      clean intermittent catheterization (CIC) after closure. METHODS: From 1987 to
      2003, 15 consecutive patients (8 boys and 7 girls) with bladder exstrophy
      underwent neonatal reconstruction. Reconstruction focused on bringing the bladder
      neck and proximal urethra intra-abdominally and meticulously closing the pelvic
      floor muscles around the urethra. Three weeks postoperatively, CIC was started
      until toilet-training age. Bladder capacity, continence status, renal anatomy and
      function, and additional urologic surgical procedures during follow-up were
      analyzed. RESULTS: Nine patients (60%) became socially continent after primary
      closure without any additional bladder neck surgery. Twelve patients (80%) were
      continent when those who underwent endoscopic bulking injection were included.
      One patient became socially continent after bladder neck reconstruction, and one
      was dry and used CIC after bladder neck reconstruction and ileocystoplasty. One
      patient remained incontinent because of the parents' refusal of surgery.
      Ultimately, of 15 patients, 14 were dry (93%) of whom 10 were completely
      continent, 3 were partially continent (dry intervals of 1 to 3 hours), and 1 was
      dry by catheterizable stoma. The bladder capacity was adequate for age in 80% of
      patients. Febrile urinary tract infection occurred in 33% of patients, and 67%
      needed endoscopy for urethral stenosis. Upper tract dilation and loss of renal
      function was not seen. CONCLUSIONS: The results of our study have shown that
      primary repair of bladder exstrophy followed by CIC has encouraging continence
      and bladder capacity rates, with preservation of the upper urinary tract and
      limited need for additional bladder neck surgery.

PMID- 16461096
TI  - Glial cell line-derived neurotrophic factor and synaptophysin expression in
      pelviureteral junction obstruction.
AB  - OBJECTIVES: To examine the expression of neuronal markers in congenital
      pelviureteral junction (PUJ) obstruction as a causative factor. The findings from
      some investigations have suggested that defective neuronal innervation may play
      an important role in the pathogenesis of PUJ obstruction. METHODS: Using specific
      antibodies, we studied the neuronal markers of specimens from 12 cases of PUJ
      obstruction and 10 normal PUJs by immunohistochemistry using glial cell line
      derived neurotrophic factor (GDNF), synaptophysin, S-100, and neurofilament.
      RESULTS: In the PUJ obstruction specimens, staining with hematoxylin-eosin and
      Masson's trichrome revealed muscular hypertrophy and an increase in collagen
      tissue and fibrosis in the lamina propria and tunica muscularis. The most
      striking finding on immunohistochemistry was the marked nuclear staining of cells
      with synaptophysin in all layers of the PUJ obstruction specimens that was
      totally absent in the normal PUJ specimens. In addition, significantly less
      intense staining for GDNF was found in the PUJ obstruction specimens compared
      with the normal PUJ specimens. The underexpression of GDNF in PUJ obstruction
      specimens was localized in the muscular layer especially. Immunohistochemical
      staining for S-100 and neurofilament showed no differences in the expression
      level of these neuronal markers in normal and PUJ obstruction specimens.
      CONCLUSIONS: Because GDNF is a survival factor for central and peripheral
      neurons, defective expression of GDNF could play an important role in the
      defective neuronal innervation of PUJ obstruction. Intense nuclear expression of
      synaptophysin in all layers of obstructed PUJ specimens suggested that obstructed
      PUJs have a serious structural abnormality.

PMID- 16461097
TI  - Extending uses of holmium:yttrium-aluminum-garnet laser--deflating blocked
      catheter balloon.
AB  - The nondeflating catheter balloon is infrequently encountered by urologists and
      can pose quite a challenge. We describe a new technique for its removal using the
      holmium:yttrium-aluminum-garnet laser when noninvasive methods have failed.

PMID- 16461098
TI  - Simple graphic method for estimation of prostate-specific antigen doubling time.
AB  - The prostate-specific antigen doubling time (PSADT) is of prognostic value in
      patients with prostate cancer, but computerized algorithms are usually required
      for PSADT estimation. We present here a simple graphic tool that can be used to
      estimate the PSADT on the basis of two increasing PSA measurements, separated by
      3 to 12 months.

PMID- 16461099
TI  - Running suture for vesicourethral anastomosis in minilaparotomy radical
      retropubic prostatectomy.
AB  - INTRODUCTION: We used a running suture method for vesicourethral anastomosis in
      patients undergoing minilaparotomy radical retropubic prostatectomy. TECHNICAL
      CONSIDERATIONS: The vesicourethral anastomosis using a single knot at the 6:30
      o'clock position is created with two steps of semicircular running suture. A
      total of 21 consecutive patients underwent this running suture method using the
      Endostitch in the hands of a single surgeon (T.M.) between March and November
      2004. The running suture procedure was completed in 15 minutes on average. After
      surgery, no urinary leakage at the anastomotic site was found. Satisfactory
      continence was achieved in the short term in 100% (0 to 1 pad per day) of cases.
      However, dilation at the anastomosis using a metal dilator was required in 2
      patients immediately after surgery. CONCLUSIONS: The running suture method is
      considered a feasible alternative in minilaparotomy radical retropubic
      prostatectomy.

PMID- 16461100
TI  - Endoscopic management of 10 separate fibroepithelial polyps arising in a single
      ureter.
AB  - INTRODUCTION: Fibroepithelial polyps of the ureter, usually of congenital or
      inflammatory origin, are rare entities. These polyps are often solitary, but
      cases of multiple polyps have also been reported. Treatment of these entities has
      evolved with emerging surgical techniques and technologies. SURGICAL TECHNIQUE:
      We describe our surgical technique for minimally invasive treatment of multiple
      polyps arising in a single ureter. The base of each polyp is ablated with a 365
      microm holmium laser fiber operating at 10 W, and each polyp is removed from the
      ureteral wall with 3F grasping forceps. Hemostasis is achieved with laser
      coagulation. Ureteral stones are removed concurrently with a 2.4F basket. A
      12/14F ureteral access sheath is used to facilitate the multiple passes of the
      ureteroscope and the removal of the polyps and stones from the proximal ureter.
      All 10 polyps were removed from the proximal portion of a single ureter. The
      ureteral stent was removed at 6 weeks, and follow-up intravenous urography at 6
      months and ureteroscopy at 11 months showed no residual polyps or stones. The
      wall of the ureter was well healed, with no evidence of stricture. CONCLUSIONS:
      We have demonstrated a specific minimally invasive technique that can be used to
      treat even highly complex cases involving upper urinary tract fibroepithelial
      polyps.

PMID- 16461101
TI  - Application of vacuum-assisted closure dressing in penile skin graft
      reconstruction.
AB  - INTRODUCTION: Skin grafting of penile defects is difficult because of the
      flexibility of the underlying recipient bed. This leads to disruption of the
      vascular ingrowth into the skin graft and compromises the results of the
      reconstruction. TECHNICAL CONSIDERATIONS: We successfully used a vacuum-assisted
      closure dressing with an incorporated wooden framework to secure penile skin
      grafts in place during the early postoperative period. CONCLUSIONS: A vacuum
      assisted closure dressing can be used successfully to secure large and
      circumferential skin grafts, as well as skin grafts on concealed penises.

PMID- 16461102
TI  - Violaceous exanthem as a manifestation of metastatic prostate cancer in skin.

PMID- 16461103
TI  - Segmental renal artery dysplasia presenting as hypertension in a child.

PMID- 16461104
TI  - Pudendal nerve branch injury during radical perineal prostatectomy.
AB  - We report the first case of direct surgical injury to a pudendal nerve branch
      during radical perineal prostatectomy. A 65-year-old patient presented with
      typical symptoms of a pudendal nerve lesion after radical perineal prostatectomy.
      As the patient did not respond to conservative treatment, surgical exploration
      and exeresis of the injured sensory branch of the pudendal nerve was necessary,
      resulting in pain improvement. Urologic surgeons should be aware of the typical
      symptoms after iatrogenic injury to the pudendal nerve or its branches. Early
      diagnosis and neurosurgical intervention are important to obtain a more favorable
      outcome.

PMID- 16461105
TI  - Polyoma virus-induced hemorrhagic cystitis in renal transplantation patient with
      polyoma virus nephropathy.
AB  - We report a biopsy proven case of hemorrhagic cystitis in a cadaveric renal
      transplant patient with hematuria. Because more and more polyoma virus infection
      is being diagnosed in kidney transplant recipients, clinicians should be aware
      that gross hematuria in a recent transplant recipient may represent polyoma virus
      induced hemorrhagic cystitis.

PMID- 16461106
TI  - Merkel cell carcinoma metastatic to testis.
AB  - Merkel cell carcinoma is an uncommon, highly aggressive, neuroendocrine tumor
      that derives from cutaneous Merkel cells involved in proprioception. It is an
      extremely aggressive and rapidly fatal cancer. We report a rare case of Merkel
      cell carcinoma metastatic to the testis with prolonged survival.

PMID- 16461107
TI  - Laparoscopic partial cystectomy for treatment of adenocarcinoma of the urachus.
AB  - The treatment of choice for urachal carcinoma has traditionally been an open
      approach, either by radical cystectomy or the more recently adopted bladder
      sparing approach of extended partial cystectomy and umbilectomy. We report for
      the first time a laparoscopic technique for an extended partial cystectomy with
      en bloc umbilectomy for the management of urachal carcinoma in a 41-year-old man.

PMID- 16461108
TI  - Eosinophilic cystitis: successful long-term treatment with montelukast sodium.
AB  - We report a rare case of eosinophilic cystitis in a 6-year-old boy who presented
      with irritative voiding symptoms, peripheral eosinophilia, and a bladder mass
      initially visualized on ultrasonography. Cystoscopy and transurethral biopsy
      confirmed the diagnosis. Complete resolution of his symptoms occurred within 1
      week of corticosteroid use and the x-ray findings improved within 6 weeks. At 6
      months of follow-up, the patient continued to require a leukotriene receptor
      antagonist (montelukast sodium) despite several attempts to discontinue its use.
      We propose that eosinophilic cystitis in children who present with peripheral
      eosinophilia will often require long-term treatment.

PMID- 16461109
TI  - Clonality of sarcomatous and carcinomatous elements in sarcomatoid carcinoma of
      the prostate.
AB  - Sarcomatoid carcinomas of the prostate are rare malignancies composed of
      carcinomatous and sarcomatous elements. Their etiology is uncertain and may
      represent a single malignant process or a mixture of two distinct malignancies.
      We report a clinical case of a patient who presented with locally advanced
      disease and was treated with hormonal and cytotoxic chemotherapy, but ultimately
      developed distant metastasis and died of the disease. A loss-of-heterozygosity
      analysis of the primary and metastatic tissues provided compelling evidence that
      the carcinomatous and sarcomatous elements are clonally related, supporting the
      hypothesis that a single malignant process underlies the etiology of sarcomatoid
      carcinoma of the prostate.

PMID- 16461110
TI  - Extraction of UroLume endoprosthesis with one-stage urethral reconstruction using
      buccal mucosa.
AB  - Long-term analyses of the UroLume Endoprosthesis have shown conflicting results
      with regard to efficacy and restricture rates. The best management of recurrent
      urethra stricture disease at the site of a previous UroLume stent is unknown. We
      describe a previously unreported technique for transperineal excision of the
      UroLume for recurrent bulbar urethral stricture disease with one-stage
      reconstruction using buccal mucosa. At 9 months of follow-up, the patient was
      voiding well with no evidence of stricture recurrence.

PMID- 16461111
TI  - Posterior urethral valves in adult with Down syndrome.
AB  - Posterior urethral valves (PUVs) in patients with Down syndrome (DS) have been
      previously described. However, no case of PUVs has been reported in an adult
      patient with DS. We report on a 40-year-old man with DS, who presented with two
      severe urinary infections and obstructive symptoms. He was found to have type 3
      PUVs associated with bladder neck sclerosis. PUV resection and bladder neck
      incision were done. Because PUVs seem to be more frequent in patients with DS,
      complete investigations should be performed, even in adults with DS, in the case
      of urinary infection or lower urinary tract symptoms.

PMID- 16461112
TI  - Intrarenal supernumerary ovary excised with partial nephrectomy.
AB  - Differentiating between complex renal cysts and cystic renal tumors is a
      difficult task that requires balancing unnecessary surgery with failure to
      diagnose cancer. We report a case of a Bosniak Class III renal mass removed by
      partial nephrectomy that was subsequently identified as an intrarenal
      supernumerary ovary. This report documents the rare anomaly of ectopic ovarian
      tissue and highlights the extraordinary combination of intrarenal location,
      lesion complexity, and surgical management with partial nephrectomy that makes
      this case unique.

PMID- 16461113
TI  - Leiomyosarcoma of scrotum--case report and review of literature.
AB  - Leiomyosarcoma of the scrotum is a rare tumor. Cutaneous and subcutaneous
      leiomyosarcomas constitute the two subtypes. We report a case of cutaneous
      leiomyosarcoma of the scrotum in a 73-year-old man. Cutaneous leiomyosarcoma
      arises from the smooth muscle of the dartos or arrectores pilorum. It is often
      mistaken for a benign lesion. We describe the clinical and pathologic features
      and review the published reports of this uncommon malignancy. It is best treated
      by wide local excision. Inguinal lymph node dissection is not advocated, unless a
      high degree of suspicion is present for lymph node metastasis. Long-term follow
      up is essential, because of the risk of delayed local recurrence and distant
      metastasis.

PMID- 16461114
TI  - Giant mullerian duct cyst with malignant transformation in 15-year-old boy.
AB  - We present a case of a giant mullerian duct cyst with components of clear cell
      adenocarcinoma in a 15-year-old boy. Complete tumor resection was achieved in two
      steps. The presented case with a combination that has never been described before
      may change the perspective of treatment approaches for this rare entity.

PMID- 16461115
TI  - Management of obstructing fungal pyelonephritis in infants.
AB  - This case report and literature review suggest that infants with renal
      obstruction due to Candida albicans pyelonephritis often require drainage, in
      addition to systemic antifungal agents, to treat the infection.

PMID- 16461116
TI  - Non-neuronal cholinergic system in human bladder urothelium.
AB  - OBJECTIVES: To evaluate the non-neuronal cholinergic system in the isolated human
      bladder. Recently, several reports have demonstrated that non-nerve-evoked
      acetylcholine (ACh) release may contribute to various pathophysiologic
      conditions. METHODS: Human bladders were obtained from 15 patients. Bladder
      strips with or without urothelium were suspended in an organ bath filled with
      Krebs-Henseleit solution. ACh release was measured using microdialysis and high
      performance liquid chromatography. The contribution of urothelium to non-nerve
      evoked ACh release was tested, and the effects of age and elevation of the
      resting tension (0 to 40 mN) on ACh release were also evaluated. Furthermore,
      choline acetyltransferase (ChAT) immunohistochemical staining of bladder was
      performed. RESULTS: Immunohistochemistry showed marked ChAT-positive staining in
      the urothelium and suburothelial region. Tetrodotoxin-insensitive non-nerve
      evoked ACh release occurred and was significantly greater in strips with than
      without urothelium. The non-nerve-evoked ACh release from strips with urothelium
      increased with age, and the positive correlation between age and release was
      significant. Stretching of the strips caused increases in non-nerve-evoked ACh
      release that was significantly greater in strips with than without urothelium.
      The stretch-induced release of non-nerve-evoked ACh increased with age.
      CONCLUSIONS: These data have demonstrated that a non-neuronal cholinergic system
      is present in the human bladder and that the urothelium/suburothelium partially
      releases ACh. We found a significant age-related and stretch-induced increase in
      non-nerve-evoked ACh release. This suggests that the non-neuronal cholinergic
      system may contribute to the physiology and pathophysiology of human bladder
      function.

PMID- 16461117
TI  - Long-term effect of experimental hypercholesterolemia on cavernosal tissues.
AB  - OBJECTIVES: To determine the effect of long-term experimental
      hypercholesterolemia on cavernosal tissues and to evaluate whether these
      alterations are reversible after improvement of hypercholesterolemia. METHODS:
      Thirty-seven New Zealand male rabbits with a mean age of 5 to 6 months and a
      weight of 2 to 2.5 kg were included in this study. The control group (group 1, n
      = 7) was fed with normal standard rabbit chow for 24 weeks, the
      hypercholesterolemia group (group 2, n = 17) was fed with a 1% pure cholesterol
      diet for 24 weeks, and the reversibility group (group 3, n = 13) was fed first
      with the 1% pure cholesterol diet for 24 weeks and then with normal standard
      rabbit chow for 12 weeks. The basal and 24-week serum lipid profiles of all
      groups and the 36-week serum lipid profiles of group 3 were measured. Core tissue
      samples 4 mm in diameter taken from formalin-fixed, paraffin-embedded tissue
      blocks of rabbit corpus cavernosum were examined for Masson trichrome
      histochemically and desmin and smooth muscle actin by the tissue array method
      using immunohistochemistry. RESULTS: Hypercholesterolemia was observed in groups
      2 and 3 at 24 weeks compared with group 1. In group 3, at 36 weeks, the
      cholesterol levels were decreased. A statistically significant (P < 0.05)
      irreversible decrease was observed in smooth muscle actin level in group 3
      (reversibility group) by immunohistochemical analysis. The decrease in desmin was
      reversible, and no significant difference was observed in collagen among the
      three groups. CONCLUSIONS: Long-term chronic effects of experimental
      hypercholesterolemia on cavernosal smooth muscles might be irreversible and this
      might alter erectile function.

PMID- 16461118
TI  - 15-deoxy-Delta12,14-prostaglandin J2 attenuates development of cyclophosphamide
      induced cystitis in rats.
AB  - OBJECTIVES: To investigate whether an endogenous prostaglandin (PG) D2
      metabolite, 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2), can attenuate cyclophosphamide
      (CYP)-induced cystitis in the rat. METHODS: Male Sprague-Dawley rats received a
      single intraperitoneal injection of CYP (200 mg/kg). In a separate group of
      animals, 15d-PGJ2 (10 and 100 microg/kg intraperitoneal bolus 10 minutes before
      and 24 hours after CYP injection) or a selective inducible nitric oxide synthase
      (iNOS) inhibitor, N-(3-(aminomethyl)benzyl)acetamidine ([1400W] 10 mg/kg
      intraperitoneal bolus 10 minutes before and 12 and 24 hours after CYP injection),
      was administered. At 48 hours after CYP injection, the rats were killed, and
      tissues were removed for evaluation of cystitis. RESULTS: CYP injection resulted
      in severe cystitis. 15d-PGJ2, as well as 1400W, significantly reduced the
      increase in plasma protein extravasation (Evans blue dye method), iNOS enzymatic
      activity, urinary excretion of nitric oxide metabolites, and myeloperoxidase
      activity in the bladder caused by CYP. Moreover, 15d-PGJ2 significantly decreased
      the cytokine interleukin-1beta in the bladder. In addition, 15d-PGJ2
      significantly reduced the degree of CYP-induced bladder tissue damage and
      increase in immunohistochemical staining for iNOS in the bladder. CONCLUSIONS:
      These results indicate that 15d-PGJ2 can attenuate the development of CYP-induced
      cystitis by suppression of cytokine production and iNOS induction. Thus,
      treatment with cyclopentenone prostaglandins such as 15d-PGJ2 may be effective
      against CYP-induced cystitis.

PMID- 16461119
TI  - Attenuation of renal fibrosis by curcumin in rat obstructive nephropathy.
AB  - OBJECTIVES: To test whether curcumin has a protective action against interstitial
      inflammation and the development of renal fibrosis in obstructive nephropathy. We
      also tested whether inhibition of nuclear factor kappa-B (NF-kappaB) and
      activator protein-1 (AP-1) by curcumin is involved in these mechanisms. METHODS:
      Adult male rats underwent unilateral ureteral obstruction. The rats were treated
      with curcumin (200 mg/kg/day or 800 mg/kg/day), NF-kappaB inhibitor pyrrolidine
      dithiocarbamate (PDTC; 200 mg/kg/day), or vehicle by gavage. Sham-operated rats
      served as controls. Seven days after unilateral ureteral obstruction, the
      activity of NF-kappaB and AP-1 was examined by electrophoretic mobility shift
      assay using nuclear protein extracts from the renal cortex. Gene expression of
      chemokines and pro-fibrotic molecules was determined by real-time reverse
      transcriptase-polymerase chain reaction. Macrophage infiltration and collagen III
      accumulation in the cortical interstitium was examined immunohistochemically.
      RESULTS: Both curcumin and PDTC significantly attenuated interstitial macrophage
      influx and renal fibrosis. Ureteral occlusion activated both NF-kappaB and AP-1
      DNA binding. Curcumin and PDTC significantly inhibited NF-kappaB activity, but
      not AP-1. Gene expression of chemokines and pro-fibrotic molecules was
      upregulated in unilateral ureteral obstruction that was attenuated by either
      curcumin or PDTC. CONCLUSIONS: Curcumin protected against the renal interstitial
      inflammation and fibrosis elicited by ureteral occlusion. Inhibition of the NF
      kappaB-dependent pathway is at least in part involved in the mechanisms, but AP-1
      inhibition is unlikely to be involved in the beneficial effects of curcumin.

PMID- 16461122
TI  - Genetic epidemiology of health disparities in allergy and clinical immunology.
AB  - The striking racial and ethnic disparities in disease prevalence for common
      disorders, such as allergic asthma, cannot be explained entirely by
      environmental, social, cultural, or economic factors, and genetic factors should
      not be ignored. Unfortunately, genetic studies in underserved minorities are
      hampered by disagreements over the biologic construct of race and logistic
      issues, including admixture of different races and ethnicities. Current
      observations suggest that the frequency of high-risk variants in candidate genes
      can differ between African Americans, Puerto Ricans, and Mexican Americans, and
      this might contribute to the differences in disease prevalence. Maintenance of
      certain allelic variants in the population over time might reflect selective
      pressures in previous generations. For example, significant associations between
      markers in certain candidate genes (eg, STAT6, ADRB2, and IFNGR1) for traits such
      as high total IgE levels observed in resistance to extracellular parasitic
      disease in one population and atopic asthma in another supports the common
      disease/common variant model for disease. Herein is a discussion of how genetic
      variants might explain, at least in part, the marked disparities observed in risk
      to allergic asthma.

PMID- 16461123
TI  - CPT coding for the allergist.

PMID- 16461121
TI  - Applying epidemiologic concepts of primary, secondary, and tertiary prevention to
      the elimination of racial disparities in asthma.
AB  - Despite medical and scientific advances, racial and ethnic disparities persist in
      US asthma morbidity and mortality rates. Progress in the elimination of these
      disparities will involve disentangling the contribution of social constructs,
      such as race, socioeconomic status, and culture, from that of the physical
      environment and genetic susceptibility. One approach to reducing asthma
      disparities is through the traditional disease prevention stages of intervention.
      As such, primary prevention targets reductions in asthma incidence; secondary
      prevention is the mitigation of established disease and involves disease
      detection, management, and control; and tertiary prevention is the reduction of
      complications caused by severe disease. Once causative factors at each level of
      disease prevention are understood, this knowledge can be translated into clinical
      practice and public health policy.

PMID- 16461124
TI  - Nitric oxide as a clinical guide for asthma management.
AB  - Asthma is a pathologically heterogeneous disease, and the phenotype is
      characterized by different types of airway inflammation. Exhaled nitric oxide
      (F(E)NO) measurements are a surrogate marker specific for eosinophilic airway
      inflammation. The latter is usually associated with steroid responsiveness, and
      hence, F(E)NO may be used to guide steroid requirements in certain clinical
      situations. High F(E)NO levels may be used to predict likely benefits with
      inhaled corticosteroid (ICS) therapy. Both high and low F(E)NO levels are
      prognostically significant when withdrawal of ICS treatment is being considered.
      Studies have shown that, just as for induced sputum, repeated F(E)NO measurements
      improve the cost-effectiveness of ICS therapy when used to guide dose
      requirements. In practice, F(E)NO measurements are useful in the management of
      severe or difficult asthma. High and low F(E)NO levels in symptomatic patients
      provide the clinician with information that enables active eosinophilic airway
      inflammation to be included or excluded. Either outcome is helpful in decision
      making. F(E)NO measurements complement the use of other tests in asthma, but more
      work is required to determine reference values and cut-points for appropriate
      interpretation.

PMID- 16461125
TI  - Grass pollen immunotherapy as an effective therapy for childhood seasonal
      allergic asthma.
AB  - BACKGROUND: Few studies have investigated the use of specific immunotherapy (SIT)
      for childhood seasonal allergic asthma. OBJECTIVE: We sought to examine the
      efficacy and safety of SIT with Alutard SQ grass pollen (Phleum pratense Alutard
      SQ; ALK-Abello, Horsholm, Denmark) in children with seasonal allergic asthma.
      METHODS: A randomized, double-blind, placebo-controlled study assessing the
      efficacy of grass pollen SIT over 2 pollen seasons was performed. Children (3-16
      years) with a history of seasonal allergic asthma sensitized to grass pollen (P
      pratense) and requiring at least 200 microg of inhaled beclomethasone equivalent
      per day were enrolled. Subjects with symptomatic asthma or rhinoconjunctivitis
      outside the grass pollen season were excluded. The primary outcome measure was a
      combined asthma symptom-medication score during the second pollen season.
      Secondary outcome measures included end-point titration skin prick testing and
      conjunctival and bronchial provocation testing to allergen, sputum eosinophilia,
      exhaled nitric oxide, and adverse events. RESULTS: Thirty-nine subjects were
      enrolled. Thirty-five subjects provided data for analysis. The use of SIT was
      associated with a substantial reduction in asthma symptom-medication score
      compared with that after placebo (P = .04). There were also significant
      reductions in cutaneous (P = .002), conjunctival (P = .02), and bronchial (P =
      .01) reactivity to allergen after SIT compared with that after placebo. The 2
      groups had similar levels of airway inflammation, despite a trend toward less
      inhaled steroid use in the active group. No serious adverse events were reported,
      and no subjects withdrew because of adverse events. CONCLUSION: The study has
      shown that SIT is effective and well tolerated in children with seasonal allergic
      asthma to grass pollen.

PMID- 16461126
TI  - IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood
      asthma.
AB  - BACKGROUND: IgE production, a hallmark of asthma and atopic disease, may be under
      genetic control. Genes of the IL-4 and IL-13 pathway, central for IgE regulation,
      have so far only been assessed in studies of single gene effects. OBJECTIVE: Here
      we analyzed combined extended haplotypes involving IL-4, IL-13, their shared
      receptor chain IL-4Ralpha, and the intracellular signal transducer and activator
      of transcription, STAT6, to assess the combined effect of single nucleotide
      polymorphisms in this important immunological signaling pathway. METHODS: We
      genotyped a large cross-sectional population of 1120 children age 9 to 11 years
      for 18 polymorphisms in the respective genes of the IL-4/IL-13 pathway. One
      polymorphism per gene was selected because of its putative functional role, and
      extended haplotypes were built in a stepwise procedure where gene-by-gene
      interactions were assessed by using a Cordell model. RESULTS: Combining
      polymorphisms in all 4 major pathway genes in a stepwise procedure, the risk for
      high serum IgE levels increased 10.8-fold (P = .02) and the risk for the
      development of asthma increased by a factor of 16.8-fold (P = .005) compared with
      the maximum effect of any single polymorphism. Significant interactions in a
      model with additive and dominant effects, for both pair and triplet combinations
      for asthma (lowest P = .005), and for pairs of polymorphisms in IgE regulation
      were observed (lowest P = .054). CONCLUSION: These data indicate that only the
      combined analyses of genetic alterations in the IL-4/IL-13 pathway reveal its
      actual significance to the development of atopy and childhood asthma.

PMID- 16461127
TI  - Downregulation of IgE antibody and allergic responses in the lung by epidermal
      biolistic microparticle delivery.
AB  - BACKGROUND: Biolistic injections provide a needle-free delivery of antigen-laden
      microparticles to the epithelium. The precision of the injection preferentially
      targets the Langerhans cell network, which, although ideal for vaccination, might
      not be suitable for the downregulation of immune responses in immunotherapy.
      OBJECTIVE: We sought to determine the ability of biolistic injection of antigen
      into the epithelium of sensitized mice to inhibit IgE antibody and lung
      inflammatory responses produced by further exposure to antigen. METHODS: Mice
      were sensitized by means of a needle injection of ovalbumin (OVA) in alum and
      given a series of biolistic injections of OVA or vehicle control, followed by a
      boost of OVA in alum. Serum IgE and IgG antibodies were measured before and after
      the boost. The mice were then challenged intranasally, and the infiltration of
      inflammatory cells was measured by means of bronchoalveolar lavage. Airway
      reactivity of the challenged mice was measured by examining responses to
      methacholine with forced oscillatory techniques. RESULTS: Biolistic injection of
      OVA into the dorsal skin of sensitized mice markedly inhibited IgE and IgG1
      antibody responses induced by boosting. IgG2a antibody responses were reduced
      rather than stimulated. The eosinophilic inflammation in the bronchoalveolar
      lavage fluid induced by intranasal challenge was also markedly inhibited. Lung
      hyperreactivity showed an initial increase and then a decrease of responsiveness
      to methacholine, with elastance returning to the level of unsensitized mice.
      Biolistic injection into the buccal epithelium was also inhibitory. CONCLUSIONS:
      Biolistic injection of allergen inhibited the boosting of IgE antibody and
      eosinophilic lung inflammatory responses without inducing T(H)1 immunity.

PMID- 16461128
TI  - Hierarchical suppression of asthma-like responses by mucosal tolerance.
AB  - BACKGROUND: Mucosal tolerance can be induced by oral or nasal administration of
      soluble proteins and results in the suppression of cellular and/or humoral immune
      responses to the specific antigen. OBJECTIVE: To compare the effect of oral or
      nasal ovalbumin administration before, during or after immunization on the
      development of cellular and humoral immune responses by using a murine asthma
      model. METHODS: To induce lung allergic inflammation, animals were immunized
      twice with ovalbumin/aluminum hydroxide gel and challenged twice with ovalbumin.
      To induce tolerance, BALB/c mice received ovalbumin by the oral or nasal routes
      for 3 consecutive days. The ovalbumin administration was initiated before (day 
      7), during (day 0), or after immunization (day 7). RESULTS: Airway eosinophilia,
      airway hyperreactivity, mucus hypersecretion, and cytokine production were
      suppressed when oral or nasal ovalbumin administration was initiated before
      immunization. Oral but not nasal ovalbumin exposure suppressed ovalbumin-specific
      nonanaphylactic IgG(1) antibodies, whereas both routes suppressed the production
      of anaphylactic IgG(1) and IgE antibodies. Mucosal ovalbumin administration at
      day 0 inhibited all T(H)2-mediated allergic parameters but not nonanaphylactic
      IgG(1) antibodies. Finally, ovalbumin exposure 7 days after immunization was
      still effective in suppressing lung allergy but not ovalbumin-specific
      anaphylactic IgG(1) and IgE antibodies. CONCLUSION: We show that the
      effectiveness of mucosal tolerance depends on route and time and presents a
      hierarchical pattern of suppression in the following order: lung allergic
      responses > anaphylactic antibodies > ovalbumin-specific IgG(1).

PMID- 16461129
TI  - Vascular endothelial growth factor-mediated induction of angiogenesis by human
      rhinoviruses.
AB  - BACKGROUND: Human rhinoviruses, major precipitants of asthma exacerbations,
      infect the lower airway epithelium inducing inflammation. The possibility that
      viral infection may mediate angiogenesis, thus contributing to airway remodeling,
      has not been evaluated. OBJECTIVE: To investigate whether epithelial infection
      with rhinovirus mediates angiogenesis in vitro, evaluate possible modulation by
      an atopic environment, and confirm angiogenic factor induction after in vivo
      rhinovirus infection. METHODS: Bronchial epithelial cells were infected with
      rhinovirus and levels of vascular endothelial growth factor (VEGF), and
      angiopoietins were measured. The angiogenic effect of epithelial products was
      assessed in in vitro models of angiogenesis. PBMCs, obtained from patients with
      atopic asthma and normal controls, were exposed to rhinovirus; the ability of
      supernatants from these cultures differentially to affect rhinovirus-mediated
      epithelial VEGF production was evaluated. VEGF levels were measured in
      respiratory secretions from patients with asthma, before and during rhinovirus
      induced exacerbations. RESULTS: Epithelial infection with rhinovirus specifically
      stimulated mRNA expression and release of VEGF, but not angiopoietins, in a time
      dependent and dose-dependent manner. Supernatants from these cultures were able
      to induce angiogenesis in vitro, significantly inhibited by a neutralizing anti
      VEGF antibody. When bronchial cells were exposed to supernatants of rhinovirus
      infected mononuclear cells from normal subjects or atopic patients with asthma,
      VEGF induction was significantly higher under the influence of the atopic
      environment. VEGF was elevated during rhinovirus-associated asthma exacerbations.
      CONCLUSION: Rhinovirus infection, a frequent event, induces VEGF production in
      bronchial epithelial cells and human airways, an effect enhanced in an atopic
      environment. Rhinovirus-associated, VEGF-mediated angiogenesis may contribute to
      airway remodeling in asthma.

PMID- 16461130
TI  - Eotaxin polymorphisms and serum total IgE levels in children with asthma.
AB  - BACKGROUND: Eotaxin (chemokine, CC motif, ligand; CCL11) is a potent eosinophil
      chemoattractant strongly implicated in the pathobiology of asthma. Genetic
      variation at the CCL11 locus has been correlated with serum total IgE, blood
      eosinophil counts, and circulating eotaxin protein levels in several case-control
      asthma studies. Family-based association studies of CCL11 genetic variants have
      not been reported to date. OBJECTIVE: To evaluate 9 common CCL11 single
      nucleotide polymorphisms (SNPs) in nuclear families ascertained through patients
      with asthma participating in the Childhood Asthma Management Program study.
      METHODS: Single nucleotide polymorphism genotyping was performed by using
      minisequencing and probe hybridization platforms. Family-based association
      analysis for asthma and 4 asthma-related intermediate quantitative phenotypes was
      performed by using FBAT. RESULTS: One SNP, -384A>G, was associated with asthma
      among African American families (P = .01). CCL11 SNPs and haplotypes were not
      associated with asthma among white or Hispanic families. Two low-frequency
      alleles in strong pairwise linkage disequilibrium, -426C and IVS2+199A, were
      associated with lower serum total IgE levels (P = .0006 and P = .009,
      respectively) in white families, whereas 2 more common variants, -576C and
      g.4438C, were associated with higher IgE levels in African American families (P =
      .01-.04). Haplotype analysis in the white cohort provided additional evidence of
      association with serum total IgE, implicating 2 haplotypes. No single SNP or
      haplotype associations were observed with blood eosinophil levels, FEV(1), or
      airway responsiveness. CONCLUSION: These findings provide further evidence that
      genetic variation at the CCL11 locus is an important determinant of serum total
      IgE levels among patients with asthma.

PMID- 16461131
TI  - Cortisol circadian rhythms and stress responses in infants at risk of allergic
      disease.
AB  - BACKGROUND: The cortisol circadian rhythm and response to stressful stimuli are
      altered in children and adults with allergic disease, including asthma. It is not
      known whether these alterations precede or follow the onset of allergic disease.
      OBJECTIVE: We sought to evaluate the cortisol circadian rhythm and stress
      response among infants at risk for the development of allergic disease. METHODS:
      Infants with and without risk factors for allergic disease were evaluated at age
      6 months. Saliva was obtained at 8 am, 2 pm, and 8 pm at home (n = 68) by parents
      when their infants were comfortable and in the clinic (n = 88) before and after
      their physical examination and vaccinations. Information regarding parental
      allergy and exposure to other children at home or in child care were obtained by
      questionnaire. RESULTS: In multivariate analysis the circadian rhythm of cortisol
      was flattened because of the lack of the expected morning surge of cortisol,
      resulting in decreased diurnal variation of cortisol in infants of mothers with
      allergy (P = .035) or asthma (P = .002) or an asthmatic father (P = .022). The
      cortisol stress response was greater in infants of mothers with allergy (P =
      .045) or asthma (P = .039), those with fewer siblings (P = .066), and those not
      entering day care early in life (P = .017). CONCLUSIONS: These alterations in
      both basal and stress levels of endogenous cortisol among infants predisposed to
      allergic disease might affect the development of allergic immune responses early
      in life through interactions with inflammatory mediators.

PMID- 16461132
TI  - Aspirin-sensitive rhinosinusitis is associated with reduced E-prostanoid 2
      receptor expression on nasal mucosal inflammatory cells.
AB  - BACKGROUND: Impaired braking of inflammatory cell cysteinyl leukotriene
      production by prostaglandin (PG) E(2) has been implicated in the pathogenesis of
      aspirin exacerbated airways disease, but the mechanism is obscure. PGE(2) acts
      via G-protein-coupled receptors, E-prostanoid (EP)(1-4,) but there is little
      information on the expression of PGE(2) receptors in this condition. OBJECTIVE:
      To address the hypothesis that expression of 1 or more EP receptors on nasal
      mucosal inflammatory cells is deficient in patients with aspirin-sensitive
      compared with nonaspirin-sensitive polypoid rhinosinusitis. METHODS: By using
      specific antibodies, immunohistochemistry, and image analysis, we measured the
      expression of EP(1-4) in nasal biopsies from patients with aspirin-sensitive (n =
      12) and nonaspirin-sensitive (n = 10) polypoid rhinosinusitis and normal controls
      (n = 9). Double-staining was used to phenotype inflammatory leukocytes expressing
      EP(1-4). RESULTS: Global mucosal expression of EP(1) and EP(2), but not EP(3) or
      EP(4), immunoreactivity was significantly elevated in aspirin-sensitive and
      nonaspirin-sensitive rhinosinusitis compared with controls (P < .03). This was
      attributable principally to elevated expression on tubulin(+) epithelial cells
      and Mucin 5 subtypes A and B (Muc-5AC(+)) goblet cells. In contrast, the
      percentages of neutrophils, mast cells, eosinophils, and T cells expressing
      EP(2), but not EP(1), EP(3), or EP(4), were significantly reduced (P < or = .04)
      in the aspirin-sensitive compared with nonaspirin-sensitive patients. CONCLUSION:
      The data suggest a possible role for PGE(2) in mediating epithelial repair in
      rhinitis and asthma. Because PGE(2) exerts a range of inhibitory actions on
      inflammatory leukocytes via the EP(2) receptor, its reduced expression in aspirin
      sensitive rhinosinusitis may be partly responsible for the increased inflammatory
      infiltrate and production of cysteinyl leukotrienes that characterize aspirin
      sensitive disease.

PMID- 16461134
TI  - Disconnection of man and the soil: reason for the asthma and atopy epidemic?
AB  - Intense search has been going on to find factors responsible for the asthma and
      atopy epidemic in Western societies. Attention has increasingly been devoted to
      environmental saprophytes, which, in addition to gut commensals, might be the
      major players in the development and fine tuning of immunologic homeostasis. This
      review outlines current evidence for the role of environmental saprophytes in the
      development of atopic disease and considers the consequences of urbanization in
      reducing contacts with soil microorganisms. The major microbial components that
      have been shown to possess immunomodulatory capacity and their respective Toll
      like receptors are also discussed, as are the possible mechanisms underlying the
      ability of saprophytes to confer protection against atopic disease.

PMID- 16461133
TI  - Efficacy and safety of specific immunotherapy with SQ allergen extract in
      treatment-resistant seasonal allergic rhinoconjunctivitis.
AB  - BACKGROUND: Specific immunotherapy is widely used to treat allergic rhinitis, but
      few large-scale clinical trials have been performed. OBJECTIVE: We sought to
      assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard
      grass pollen in patients with moderately severe seasonal allergic rhinitis
      inadequately controlled with standard drug therapy. METHODS: We performed a
      double-blind, randomized, placebo-controlled study of 410 subjects (203
      randomized to 100,000 standardized quality units [SQ-U] maintenance, 104 to
      10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed
      treatment. Groups were well matched for demographics and symptoms. RESULTS:
      Across the whole pollen season, mean symptom and medication scores were 29% and
      32% lower, respectively, in the 100,000-SQ-U group compared with those in the
      placebo group (both P < .001). Over the peak pollen season, mean symptom and
      medication scores were 32% and 41% lower, respectively, than those in the placebo
      group. The 10,000-SQ-U group had 22% less symptoms than the placebo group over
      the whole season (P < .01), but medication scores reduced by only 16% (P = .16).
      Quality-of-life measures confirmed the superiority of both doses to placebo.
      Local and delayed side effects were common but generally mild. Clinically
      significant early and delayed systemic side effects were confined to the 100,000
      SQ-U group, but no life-threatening reactions occurred. CONCLUSIONS: One season
      of immunotherapy with Alutard grass pollen reduced symptoms and medication use
      and improved the quality of life of subjects with moderately severe hay fever.
      The 100,000-SQ-U regimen was more effective, but the 10,000-SQ-U regimen caused
      fewer side effects.

PMID- 16461135
TI  - The influence of health disparities on individual patient outcomes: what is the
      link between genes and environment?

PMID- 16461136
TI  - The widening black/white gap in asthma hospitalizations and mortality.
AB  - BACKGROUND: Large racial differences in asthma morbidity and mortality have
      prompted research on new interventions, public awareness, and health policy
      efforts in the past decade. OBJECTIVE: We sought to characterize recent trends in
      US asthma hospitalization and mortality for black and white children and adults
      during the period from 1980 through 2002. METHODS: We conducted a successive
      representative national cohort study of US residents ages 5 to 34 years using
      data from the National Hospital Discharge Survey and the US vital statistics
      system. Outcome measures included black/white (B/W) asthma hospitalization and
      mortality rates, rate ratios, and rate differences. RESULTS: For asthma
      hospitalizations from 1980 through 2002, children ages 5 to 18 years had a 50%
      increase in the B/W rate ratio, and the rate difference increased from 22.8 to
      28.3 hospitalizations per 10,000 population. For young adults ages 19 to 34
      years, the B/W rate ratio increased from 2.3 to 2.8, and the rate difference
      decreased from 9.6 to 7.9 hospitalizations per 10,000 population. For asthma
      mortality from 1980 through 2001, children ages 5 to 19 years had a large
      increase in the B/W rate ratio from 4.5 to 5.6 and in the rate difference from
      5.6 to 8.1 deaths per 1,000,000 population. There did not appear to be a
      significant change in the B/W differences for adults ages 20 to 34 years.
      CONCLUSIONS: For children, there have been notable increases in asthma B/W
      differences in hospitalizations and mortality since 1980, whereas for adults the
      increase has been smaller. National efforts to improve asthma care over the past
      decade do not appear to have reduced this B/W gap. When treating children with
      asthma, it is important to consider the racial-ethnic factors that might lead to
      avoidable hospitalizations and premature mortality.

PMID- 16461137
TI  - Cost-effectiveness of inhaled steroids in asthma: impact of effect on bone
      mineral density.
AB  - BACKGROUND: The effects of inhaled corticosteroid (ICS) preparations on bone
      health have been debated. Multiple analyses have been published examining the
      question, with mixed results. OBJECTIVES: We examined how assumptions about the
      effect of ICS on bone mineral density (BMD) influence the cost-effectiveness of
      ICS in asthma. METHODS: We developed a mathematical simulation model to estimate
      clinical outcomes and costs for a cohort with mild/moderate asthma. The analysis
      conformed to reference case recommendations of the US Panel on Cost-Effectiveness
      in Health and Medicine. Sensitivity analysis evaluated the stability of our
      results to uncertainty in treatment duration, age at treatment, and ICS dose.
      RESULTS: Assuming a dose of 200 microg twice per day of ICS, a literature-based
      average effect of ICS on BMD and a 10-year time horizon, we observed a minimal
      increase in the costs attributed to hip fracture and incremental cost
      effectiveness ratio of $26,000 per quality-adjusted life-year and $14.00 per
      symptom-free day gained. Over an extended the time horizon (lifetime), the
      incremental cost effectiveness ratio increased to $42,000/quality-adjusted life
      year. Only under a scenario of high-dose ICS, a lifetime horizon, and a large
      effect of ICS on BMD did the potential impact of ICS on BMD dramatically affect
      the economic attractiveness of therapy. CONCLUSION: To minimize any potential
      impact, use of the lowest effective dose of ICS and measures to target and
      intervene in high-risk individuals are warranted. However, ICS therapy in
      mild/moderate asthma compares favorably with commonly accepted interventions over
      a wide range of assumptions regarding this treatment and its effects on BMD.

PMID- 16461138
TI  - Anaphylaxis, killer allergy: long-term management in the community.
AB  - Traditionally, physicians are trained to diagnose and treat anaphylaxis as an
      acute emergency in a health care setting. In addition to this crucial and time
      honored role, we should be cognizant of our wider responsibility to (1) provide a
      risk assessment for individuals with anaphylaxis, (2) prevent future anaphylaxis
      episodes by developing long-term personalized risk reduction strategies for
      affected individuals, and (3) emphasize anaphylaxis education. Risk assessment
      should include verification of the trigger factor or factors for the anaphylaxis
      episode by obtaining a comprehensive history and performing relevant
      investigations, including allergen skin tests and measurement of allergen
      specific IgE in serum. In addition, the potential effect of comorbidities and
      concurrently administered medications on the recognition and emergency treatment
      of subsequent episodes should be determined. Risk reduction strategies should be
      personalized to include information about avoidance of specific triggers and
      initiation of relevant specific preventive treatment (eg, venom immunotherapy).
      At-risk individuals should be coached in the use of self-injectable epinephrine
      and equipped with an anaphylaxis emergency action plan and with accurate medical
      identification. Anaphylaxis education should be provided for these individuals,
      their families and caregivers, health care professionals, and the general public.
      Further development of an optimal diagnostic test for anaphylaxis and of tests
      and algorithms to predict future risk and prevent fatality are urgently needed.

PMID- 16461139
TI  - Second symposium on the definition and management of anaphylaxis: summary report-
      Second National Institute of Allergy and Infectious Disease/Food Allergy and
      Anaphylaxis Network symposium.
AB  - There is no universal agreement on the definition of anaphylaxis or the criteria
      for diagnosis. In July 2005, the National Institute of Allergy and Infectious
      Disease and Food Allergy and Anaphylaxis Network convened a second meeting on
      anaphylaxis, which included representatives from 16 different organizations or
      government bodies, including representatives from North America, Europe, and
      Australia, to continue working toward a universally accepted definition of
      anaphylaxis, establish clinical criteria that would accurately identify cases of
      anaphylaxis with high precision, further review the evidence on the most
      appropriate management of anaphylaxis, and outline the research needs in this
      area.

PMID- 16461140
TI  - Sublingual epinephrine tablets versus intramuscular injection of epinephrine:
      dose equivalence for potential treatment of anaphylaxis.
AB  - BACKGROUND: Epinephrine autoinjectors are underused in the emergency treatment of
      anaphylaxis in the community, perhaps in part because of fear of needles.
      OBJECTIVES: To determine the sublingual epinephrine dose from a novel fast
      disintegrating tablet required to achieve epinephrine plasma concentrations
      (EPPCs) similar to those obtained after epinephrine 0.3 mg intramuscular
      injection. METHODS: In a prospective 5-way crossover study, sublingual tablets
      containing epinephrine 0, 10, 20, and 40 mg, and epinephrine 0.3 mg intramuscular
      in the thigh (EpiPen) were compared in a validated rabbit model. Blood samples
      were collected before dosing and 5, 10, 15, 20, 30, 40, 60, 90, 120, 150, and 180
      minutes afterward. EPPCs were measured by using high-performance liquid
      chromatography-electrochemical detection. Pharmacokinetic parameters were
      calculated by using WinNonlin. RESULTS: The area under the curve (AUC), maximum
      concentration (C(max)), and time at which C(max) was achieved (T(max)) did not
      differ significantly (P > .05) after epinephrine 40 mg (AUC = 1861 +/- 537
      ng/mL/min, C(max) = 31.0 +/- 13.1 ng/mL, and T(max) = 9 +/- 2 minutes) and
      epinephrine 0.3 mg intramuscular (AUC = 2431 +/- 386 ng/mL/min, C(max) = 50.3 +/-
      17.1 ng/mL, and T(max) = 21 +/- 5 minutes). The AUC after tablets containing
      epinephrine 0 mg (AUC = 472 +/- 126 ng/mL/min), epinephrine 10 mg (AUC = 335 +/-
      152 ng/mL/min), and epinephrine 20 mg (AUC = 801 +/- 160 ng/mL/min) did not
      differ significantly from each other, but were significantly lower (P < .05) than
      the AUC after epinephrine 0.3 mg intramuscularly. CONCLUSION: Sublingual
      administration of epinephrine 40 mg from this tablet formulation resulted in
      EPPCs similar to those obtained after epinephrine 0.3 mg intramuscular injection
      in the thigh. CLINICAL IMPLICATIONS: For treatment of anaphylaxis in the
      community, self-injectable epinephrine is underused. This novel, fast
      disintegrating epinephrine tablet formulation for sublingual administration is a
      feasible alternative that warrants further development.

PMID- 16461141
TI  - Immediate allergic reactions to cephalosporins: evaluation of cross-reactivity
      with a panel of penicillins and cephalosporins.
AB  - BACKGROUND: Allergy to cephalosporins has mainly been evaluated in the context of
      patients with confirmed penicillin allergy. The problem of studying cross
      reactivity in subjects primarily sensitized to cephalosporins and potentially
      allergic to penicillins has not been sufficiently addressed. OBJECTIVE: To
      evaluate the in vitro IgE response and cross-reactivity to betalactams in
      patients with immediate allergic reactions to cephalosporins. METHODS: The study
      included 24 patients with immediate allergic reactions to cephalosporins and RAST
      positive to at least 1 cephalosporin. Skin testing and RAST were performed with a
      panel of penicillins and cephalosporins. RAST inhibition assay with different
      monomeric conjugates of penicillin and cephalosporin was performed to establish
      cross-reactivity. RESULTS: The culprit cephalosporins were cefaclor (N = 7),
      cefonicid (N = 1), cefotaxime (N = 2), ceftazidime (N = 2), ceftriaxone (N = 3),
      and cefuroxime (N = 9). Two patients had a positive skin test result to
      penicillin determinants, and 22 patients had a negative result to penicillin
      determinants and tolerated benzylpenicillin administration. Of these 22, 19 had a
      positive skin test result to cephalosporins and divided into patients reacting
      only to the culprit cephalosporin (63.2%) and those reacting to more than 1
      cephalosporin (36.8%). RAST and RAST inhibition studies confirmed that the side
      chain at the R1 position is crucial for recognition. CONCLUSION: The R1 side
      chain rather than the betalactam structure, shared by penicillins and
      cephalosporins, seems to play a dominant role in determining the specificity of
      immunologic reactions to cephalosporins. Thus, penicillin can be administered
      safely to patients allergic to cephalosporins and with a negative skin test
      result to penicillin determinants.

PMID- 16461142
TI  - IL-31: a new link between T cells and pruritus in atopic skin inflammation.
AB  - BACKGROUND: IL-31 is a novel T-cell-derived cytokine that induces severe pruritus
      and dermatitis in transgenic mice, and signals through a heterodimeric receptor
      composed of IL-31 receptor A and oncostatin M receptor. OBJECTIVE: To investigate
      the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases.
      METHODS: The expression of IL-31 was analyzed by quantitative real-time PCR in
      skin samples of healthy individuals and patients with chronic inflammatory skin
      diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic
      dermatitis patients after allergen or superantigen exposure, as well as in
      stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer
      was investigated by DNA microarray analysis. RESULTS: IL-31 was significantly
      overexpressed in pruritic atopic compared with nonpruritic psoriatic skin
      inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the
      most pruritic forms of chronic skin inflammation. In vivo, staphylococcal
      superantigen rapidly induced IL-31 expression in atopic individuals. In vitro,
      staphylococcal enterotoxin B but not viruses or T(H)1 and T(H)2 cytokines induced
      IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes
      expressed significantly higher IL-31 levels compared with control subjects. IL-31
      receptor A showed most abundant expression in dorsal root ganglia representing
      the site where the cell bodies of cutaneous sensory neurons reside. CONCLUSION:
      Our findings provide a new link among staphylococcal colonization, subsequent T
      cell recruitment/activation, and pruritus induction in patients with atopic
      dermatitis. Taken together, these findings show that IL-31 may represent a novel
      target for antipruritic drug development.

PMID- 16461143
TI  - IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T
      cells in patients with atopic dermatitis.
AB  - BACKGROUND: IL-31 is a newly discovered T-cell cytokine that, when overexpressed
      in mice, results in pruritus and skin dermatitis resembling human atopic
      dermatitis (AD). OBJECTIVE: We sought to investigate the expression of IL-31 and
      IL-31 receptor A (IL-31RA) in skin biopsy specimens and peripheral blood cells
      from patients with AD and healthy individuals. METHODS: Expression of IL-31 and
      IL-31RA was evaluated in skin biopsy specimens from patients with AD and healthy
      individuals by means of immunohistochemistry and RT-PCR. IL-31 protein production
      by skin-homing cutaneous lymphocyte antigen (CLA)-positive T cells was also
      assessed. RESULTS: IL-31RA protein was expressed by keratinocytes and
      infiltrating macrophages in skin biopsy specimens from patients with AD.
      Comparisons between skin from patients with AD and healthy skin showed IL-31RA
      expression at higher levels on epidermal keratinocytes in AD samples.
      Infiltrating cells, more numerous in skin from patients with AD compared with
      that of healthy individuals, expressed IL31 mRNA. Histomorphometric analysis of
      these cells indicated they were of the lymphocytic lineage, with the majority of
      cells staining positive for CLA and CD3. IL31 mRNA and protein expression is
      largely restricted to CD45RO(+) (memory) CLA(+) T cells in peripheral blood of
      patients with AD and healthy volunteers. Moreover, circulating CLA(+) T cells
      from patients with AD, but not from patients with psoriasis, are capable of
      producing higher levels of IL-31 compared with CLA(+) T cells from healthy
      individuals. However, the average levels of IL-31 were not significantly
      different between patients with AD and healthy individuals. CONCLUSION: We
      provide evidence that IL-31 expression is associated with CLA(+) T cells and
      might contribute to the development of AD-induced skin inflammation and pruritus.

PMID- 16461144
TI  - Napins, 2S albumins, are major allergens in oilseed rape and turnip rape.
AB  - BACKGROUND: Children with IgE-mediated allergy to foods frequently react to seeds
      of oilseed rape (Brassica napus ssp. oleifera) and turnip rape (Brassica rapa
      ssp. oleifera) in skin prick tests (SPTs). Sensitization pathways are not known.
      OBJECTIVE: We identified possible major allergens in oilseed rape and turnip rape
      using sera from 72 atopic children (mean age, 3.3 years) with positive SPT
      responses to oilseed rape and turnip rape. METHODS: Allergens from oilseed rape
      and turnip rape seed extracts were purified by using gel filtration and cation
      exchange chromatography and characterized by means of reversed-phase
      chromatography, N-terminal amino acid sequencing, and matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry. IgE binding of sera from
      72 children with positive SPT reactions to oilseed rape and turnip rape and 72
      age- and sex-matched atopic control subjects with negative SPT responses were
      analyzed by means of IgE ELISA and immunoblotting. In vivo reactivity of the
      purified allergens was tested with SPTs in 6 children. RESULTS: In IgE
      immunoblotting and IgE ELISA major reactivity was to a group of homologous,
      approximately 9.5- to 14.5-kd proteins. These allergens were identified as 2S
      albumins, also known as napins, by means of N-terminal amino acid sequencing. In
      ELISA approximately 80% of the patients had IgE to purified napins from both
      plants. In SPTs purified napins caused positive reactions in all 6 children
      tested. CONCLUSIONS: This study shows that 2S albumins in oilseed rape and turnip
      rape are new potential food allergens. Further studies are needed to clarify the
      routes of exposure and mechanisms of sensitization.

PMID- 16461145
TI  - Wheat allergy: a double-blind, placebo-controlled study in adults.
AB  - BACKGROUND: Wheat is believed to be an uncommon cause of food allergy in adults;
      the number of studies that address IgE mediated wheat allergy in adults is all
      too few. OBJECTIVE: Determine how many subjects with a history of wheat allergy
      have real allergy by double-blind, placebo-controlled food challenge; identify
      the symptoms manifested during the challenge; determine the lowest provocation
      dose; determine the performance characteristics of wheat skin prick test and
      specific IgE; identify subjects with real wheat allergy for potential
      immunoblotting studies. METHODS: Patients underwent skin test with commercial
      wheat extract; specific wheat IgE was determined. Subjects were challenged with
      25 g wheat. Subjects who were positive to raw wheat challenge underwent cooked
      wheat challenge. RESULTS: Thirty-seven double-blind placebo-controlled wheat
      challenges were performed on 27 patients. A total of 13 of 27 (48%) patients had
      a positive result. Eleven subjects with positive raw wheat challenge underwent
      cooked wheat challenge: 10 were positive. The provocation dose range was 0.1 to
      25 g. Twenty-seven percent of the subjects allergic to wheat had a provocation
      dose that was < or =1.6 g. CONCLUSION: Wheat causes real food allergy in adults.
      More than a quarter of the patients allergic to wheat reacted to less than 1.6 g
      wheat. Specific IgE was more sensitive than skin test for wheat; however,
      specificity and predictive values were low for both tests. Thus, these tests
      should not be used to validate diagnosis of wheat allergy.

PMID- 16461146
TI  - Breast milk fatty acids and allergic disease in preschool children: the
      Prevention and Incidence of Asthma and Mite Allergy birth cohort study.
AB  - BACKGROUND: Better understanding of the association between early life lipid
      intakes and the development of allergic diseases is needed. OBJECTIVE: We
      prospectively studied breast milk content of n-6, n-3, and trans fatty acids in
      relation to allergic symptoms at the ages of 1 and 4 years. METHODS: Fatty acid
      content was determined in breast milk samples of 265 (158 allergic and 107
      nonallergic) mothers of children participating in the Prevention and Incidence of
      Asthma and Mite Allergy study. Outcome variables studied were parental reported
      eczema at age 1 year, eczema at age 4 years, asthma at age 4 years, and, in a
      subgroup of 133 children, sensitization at age 4 years. RESULTS: In children of
      mothers with allergy, breast milk n-3 long chain polyunsaturated fatty acids and
      the ratio between n-3 and n-6 long chain polyunsaturated fatty acids were
      inversely associated with asthma and with persistent symptoms (eczema at age 1
      year and eczema at age 4 years and/or asthma at age 4 years), but no associations
      between breast milk fatty acids and sensitization were observed. In children of
      mothers with allergy, also trans fatty acids tended to be inversely associated
      with allergic symptoms. In children of mothers without allergy, no associations
      between breast milk fatty acids and allergic symptoms were observed, but alpha
      linolenic acid (18:3n-3) was positively associated with sensitization.
      CONCLUSION: In susceptible infants, the risk to develop allergic symptoms, but
      not the risk of sensitization, was modified by intake of n-3 long chain
      polyunsaturated fatty acids through breast milk.

PMID- 16461147
TI  - Determination of no-observed-adverse-effect levels and eliciting doses in a
      representative group of peanut-sensitized children.
AB  - BACKGROUND: Current labeling practices for allergenic foods like peanut can be
      inadequate. For future regulatory and industry guidelines, information on no
      observed-adverse-effect levels (NOAELs) and eliciting doses (EDs) for allergenic
      foods is necessary. OBJECTIVE: To determine NOAEL and ED in a representative
      group of peanut-sensitized children, relate these data to history and
      sensitization, and evaluate the outcome of dietary management. METHODS: From an
      overall eligible group of 96 peanut-sensitized children, a representative group
      of 27 was evaluated by questionnaires, skin prick test, determination of specific
      IgE, and double-blind placebo-controlled food challenge (DBPCFC) with peanut
      according to the international consensus protocol, with 9 doses ranging from 10
      microg to 3 g peanut flour. Dietary management was evaluated over a 12-month
      period. RESULTS: Twenty-two children (81%) had a positive DBPCFC. The NOAEL in
      this group was 1 mg peanut flour, corresponding to 2 mg whole peanut. The ED for
      subjective symptoms (10 mg to 3 g) was significantly lower than for objective
      symptoms (100 mg to 3 g; P = .002). Severe reactions occurred only at high doses.
      EDs were not correlated to previous reactions by history, skin prick test, or
      specific IgE levels. All patients with a positive DBPCFC were advised to follow a
      strict diet. During the follow-up period, 10 patients had a less strict diet
      likely containing traces of peanut. In 3 cases, a mild reaction occurred with
      food products labeled "may contain peanut." CONCLUSION: The NOAEL in a
      representative group of children with peanut allergy was 2 mg. Dietary compliance
      in half of this group was inadequate.

PMID- 16461148
TI  - Long-lasting reactivity and high frequency of drug-specific T cells after severe
      systemic drug hypersensitivity reactions.
AB  - BACKGROUND: Drug-reactive T cells are involved in most drug-induced
      hypersensitivity reactions. The frequency of such cells in peripheral blood of
      patients with drug allergy after remission is unclear. OBJECTIVE: We determined
      the frequency of drug-reactive T cells in the peripheral blood of patients 4
      months to 12 years after severe delayed-type drug hypersensitivity reactions, and
      whether the frequency of these cell differs from the frequency of tetanus toxoid
      reactive T cells. METHODS: We analyzed 5 patients with delayed-type drug
      hypersensitivity reactions, applying 2 methods: quantification of cytokine
      secreting T cells by enzyme-linked immunospot (ELISpot), and fluorescent dye 5,6
      carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity distribution
      analysis of drug-reactive T cells. RESULTS: Frequencies found were between 0.02%
      and 0.4% of CD4(+) T cells reacting to the respective drugs measured by CFSE
      analysis, and between 0.01% and 0.08% of T cells as determined by ELISpot.
      Reactivity was seen neither to drugs to which the patients were not sensitized
      nor in healthy individuals after stimulation with any of the drugs used.
      CONCLUSION: About 1:250 to 1:10,000 of T cells of patients with drug allergy are
      reactive to the relevant drugs. This frequency of drug-reactive T cells is higher
      than the frequency of T cells able to recognize recall antigens like tetanus
      toxoid in the same subjects. A substantial frequency could be observed as long as
      12 years later in 1 patient even after strict drug avoidance. Patients with
      severe delayed drug hypersensitivity reactions are therefore potentially prone to
      react again to the incriminated drug even years after strict drug avoidance.

PMID- 16461149
TI  - Two cases of accidental epinephrine injection into a finger.

PMID- 16461150
TI  - A second dose of epinephrine for anaphylaxis: how often needed and how to carry.

PMID- 16461151
TI  - Systemic reactions during skin tests with beta-lactams: a risk factor analysis.

PMID- 16461152
TI  - Seasonal sensorineural hearing loss associated with allergic rhinitis: a case
      report.

PMID- 16461154
TI  - Ethics of placebos in clinical asthma trials.

PMID- 16461155
TI  - Infant formulas for primary allergy prevention.

PMID- 16461157
TI  - Alternaria alternata antigens in US homes.

PMID- 16461158
TI  - Bronchial obstruction: a limited, out-of-fashion approach to measure treatment
      efficacy in childhood asthma?

PMID- 16461161
TI  - Anaphylactic reaction and antibodies to DX-88 (kallikrein inhibitor) in a patient
      with hereditary angioedema.

PMID- 16461162
TI  - Reality testing: in reply to Fuhlbrigge and Sullivan.

PMID- 16461165
TI  - The Bone and Joint Decade: 2000 to 2010.

PMID- 16461167
TI  - The relative responsiveness of 3 different types of clinical outcome measures on
      chiropractic patients with low back pain.
AB  - OBJECTIVE: The purpose of this study is to compare the responsiveness/sensitivity
      of 3 fundamentally different types of outcome measures in low back pain. METHOD:
      This study is a longitudinal evaluation of outcome measures. Thirty-one private
      chiropractic practices in Denmark participated in this study. The outcome
      measures chosen for this study are the serial measurements using the Roland
      Morris Disability Questionnaire, the patient's prospective global assessment on a
      visual analog scale, and the patient's retrospective global assessment of
      improvement on a visual analog scale. RESULTS: The 3 outcome measures differed
      significantly in their ability to register clinical improvement, with the
      retrospective global assessment of improvement being the most responsive.
      CONCLUSION: More research is needed in this area, and caution must be taken in
      choosing outcome measures for randomized clinical trials on low back pain.

PMID- 16461168
TI  - Improvement after chiropractic care in cervicocephalic kinesthetic sensibility
      and subjective pain intensity in patients with nontraumatic chronic neck pain.
AB  - OBJECTIVE: The objective of this study was to examine alteration in head
      repositioning accuracy (HRA), range of motion, and pain intensity in patients
      with chronic cervical pain syndrome without a history of cervical trauma.
      METHODS: The study was a prospective, randomized, controlled trial. Forty-one
      patients with chronic cervical pain were randomly assigned to either a control
      group or a chiropractic treatment group. All patients were clinically examined,
      given general information on cervical pain, and provided with training
      instructions based on the clinical evaluation. The treatment included sessions
      with high-velocity and low-amplitude manipulation, proprioceptive neuromuscular
      facilitation, ischemic compression of myofascial trigger points, and spinal
      rehabilitation exercises aiming to normalize cervical range of motion (CROM) and
      HRA. Subjective pain intensity, cervical kinesthetic sensibility, and CROM were
      recorded before and after the study period. RESULTS: There was no difference
      between the treatment patients and the control subjects at the beginning with
      regard to age, sex, subjective pain intensity, range of motion, and HRA. At the 5
      week follow-up, the treatment patients showed significant reductions in pain and
      improvement of all HRA aspects measured whereas the control subjects did not show
      any reduction in pain and improvement in only one HRA aspect. No significant
      difference was detected in CROM. CONCLUSIONS: The results of this study suggest
      that chiropractic care can be effective in influencing the complex process of
      proprioceptive sensibility and pain of cervical origin. Short, specific
      chiropractic treatment programs with proper patient information may alter the
      course of chronic cervical pain.

PMID- 16461169
TI  - Efficacy of treating low back pain and dysfunction secondary to osteoarthritis:
      chiropractic care compared with moist heat alone.
AB  - OBJECTIVE: To evaluate the efficacy of chiropractic spinal manipulation, manual
      flexion/distraction, and hot pack application for the treatment of low back pain
      from osteoarthritis (OA) compared with moist heat alone. METHODS: Two hundred
      fifty-two patients with low back pain secondary to OA were randomly assigned to
      either the treatment group (moist hot pack plus chiropractic care) or the moist
      heat group subjects, which attended 20 treatment sessions over several weeks. At
      sessions 1, 5, 10, 15, and 20, they rated pain using a visual analog pain scale,
      activities of daily living using the Oswestry Low Back Pain Questionnaire, and a
      range of motion (ROM) using the J-Tech Dual Digital Inclinometer (JTECH Medical
      Model no. AA036). RESULTS: Session I ratings indicated that the two groups were
      equivalent on all pain and flexion scores. The treatment group reported greater
      and more rapid pain reduction and greater and more rapid ROM improvement than the
      moist heat group. The treatment group also had greater improvements than the
      moist heat group in daily living activities in 4 of the 9 areas measured.
      CONCLUSION: Chiropractic care combined with heat is more effective than heat
      alone for treating OA-based lower back pain. Pain reduction occurs more rapidly
      and to a greater degree, and ROM increases more rapidly and to a greater degree.

PMID- 16461170
TI  - The effect of seat belt use on the cervical electromyogram response to whiplash
      type impacts.
AB  - OBJECTIVE: The objective of this study was to determine the effect of a standard
      3-point lap-and-shoulder seat belt and car seat on the electromyogram (EMG)
      response of the cervical muscles to increasing low-velocity impacts in comparison
      with that of a rigid seat and 5-point restraint. METHODS: Seventeen healthy
      volunteers were subjected to rear, frontal, right and left lateral and bilateral
      anterolateral, and posterolateral impacts with an acceleration varying from 4.4
      to 16.8 m/s(2) while in a car seat with lap-and-shoulder seat belt. RESULTS: For
      rear-end impacts, whether straight on, right posterolateral, or left
      posterolateral, all muscles generated 50% or less of the maximal voluntary
      contraction (MVC) EMG. In straight-on rear impacts, the sternocleidomastoid was
      symmetrically the most active; however, in posterolateral impacts, the
      sternocleidomastoid contralateral to impact direction was more active than its
      counterpart. For a right lateral impact, at the highest acceleration, the left
      splenius capitis generated 47% of its MVC and the left trapezius did 46% of its
      MVC. In a left lateral impact, the right splenius capitis generated 48% of its
      MVC and the right trapezius did 57% of its MVC. In a straight-on frontal impact,
      the left trapezius generated 35% of its MVC and the right trapezius did 48% of
      its MVC. In a left anterolateral impact, the right splenius generated 60% of its
      MVC and the right trapezius did 66% of its MVC. Similarly, in a right
      anterolateral impact, the contralateral splenius muscle increased its activity to
      52% of its MVC and the left trapezius was at 52% of its MVC. CONCLUSIONS:
      Compared with previously reported impact studies with a rigid seat and 5-point
      harness, the use of a 3-point lap-and-shoulder seat belt with a standard car seat
      did not appear to adversely affect cervical muscle response. In very-low-velocity
      and low-velocity impact experiments, seat belt and seat type may not
      significantly alter cervical EMG and kinematics.

PMID- 16461171
TI  - The accuracy of ultrasonic indentation in detecting simulated bone displacement:
      a comparison of three techniques.
AB  - PURPOSE: Palpation is used most commonly to assess tissue stiffness despite its
      well-known deficiencies. As an improvement, a mechanical technique known as
      ultrasonic indentation has been proposed. The purpose of this study was to
      compare the accuracy of 3 ultrasonic indentation techniques in quantifying bone
      displacement in a specially constructed tissue simulator. METHODS: Three
      ultrasonic indentation techniques were tested for their accuracy: a rigid,
      laboratory-based method (rigid), a less rigid system actuated by hand (assisted),
      and a totally free-hand system (handheld). Each indentation technique was applied
      on a tissue simulator, which consisted of a deformable phantom overlying a
      displaceable piston to simulate soft tissue overlying bone. Measures of piston
      (ie, bone) displacement obtained by each indentation technique were compared with
      a gold standard of piston displacement to determine the accuracy of each
      technique. Statistical tests were used to determine if differences between
      experimental and reference measures of piston displacement were significant.
      RESULTS: When indented, phantom deformation preceded piston displacement because
      of unequal stiffness between the two. The rigid and assisted indentation
      techniques showed the best accuracy for measuring simulated bone displacement.
      Differences in accuracy between the rigid and assisted techniques were
      insignificant. The accuracy of the handheld technique was significantly less than
      the rigid and assisted techniques. CONCLUSIONS: The clinical utility of assisted
      ultrasonic indentation should be explored given its accuracy and the excessive
      size, cost, and complexity of the rigid technique. The large error magnitude of
      the handheld technique may exclude it from clinical use now.

PMID- 16461172
TI  - Reliability of a clinical test for deep cervical flexor endurance.
AB  - OBJECTIVE: Endurance deficiencies of the deep cervical flexors are associated
      with pain, increased lordosis, and headache. A need exists for reliable clinical
      tests of flexor endurance. This study determined intrarater and interrater
      reliability of such a test in persons without neck pain. METHODS: Twenty-seven
      subjects (aged 20-35 years) without a history of neck pain or injury were tested.
      Supine subjects were timed in maintaining a position involving two components:
      (1) craniovertebral flexion (chin tuck) and (2) lower cervical flexion (holding
      the occiput at a fixed height). Each subject was examined twice by 3 different
      examiners with 1 to 2 days between trials. RESULTS: When two values were
      averaged, interrater reliability for the 3 testers was 0.83, 0.85, and 0.88.
      Intrarater reliability values were 0.78 and 0.85 for tests 1 and 2, respectively.
      CONCLUSIONS: The flexor endurance test showed good intertester and intratester
      reliability when two values were averaged and, thus, may represent a useful
      clinical tool for practitioners involved in treating and preventing neck pain.

PMID- 16461174
TI  - A pilot study comparing the effects of spinal manipulative therapy with those of
      extra-spinal manipulative therapy on quadriceps muscle strength.
AB  - OBJECTIVE: The objective of this study was to assess whether tibiofemoral joint
      manipulation is as effective as sacroiliac (SI) joint manipulation in increasing
      quadriceps muscle strength. DESIGN AND SETTING: Twenty subjects were divided into
      two groups of 10. After all base measurements of the maximum voluntary force of
      the quadriceps muscles were taken, subjects in group A received tibiofemoral
      joint manipulation and those in group B received ipsilateral SI joint
      manipulation. After these treatments, the maximum voluntary forces of the
      subjects' quadriceps muscles were retested. RESULTS: A significant improvement (P
      = .05) in quadriceps muscle strength was noted in the subjects who received an SI
      joint manipulation. CONCLUSION: This study showed a significant change within the
      SI joint manipulation group before and after the manipulation but did not show
      any significant difference between the groups (tibiofemoral joint vs SI joint
      manipulation) in increasing quadriceps muscle strength.

PMID- 16461173
TI  - Vastus medialis: anatomical and functional considerations and implications based
      upon human and cadaveric studies.
AB  - OBJECTIVE: To provide an electrophysiological and functional description of the
      vastus medialis (VM) and contrast it to an anatomical description. METHODS: Motor
      points of all superficial portions of the quadriceps were identified on the
      dominant side of 8 human subjects and electrically stimulated to achieve a light
      contraction to trace and measure the orientation of the fibers. Electromyography
      of the VM was then recorded over 2 motor points during isometric and isokinetic
      maximum knee extensions. An independent laboratory dissected 39 cadaveric
      specimens focusing on fiber orientations and distal insertions of the VM.
      RESULTS: Results revealed 5 motor points for the quadriceps: 1 point for the
      vastus lateralis, 1 point for the rectus femoris (RF), and 3 points for the VM.
      The 3 VM motor points suggest 3 separate groups of fibers: proximal (pf), median
      (mf), distal (df). Fiber orientations ranged from 45 degrees for VMpfs to 55
      degrees for VMdfs. Motor point stimulation and anatomical dissection clearly
      showed that the VMpfs and VMmfs were inserted on a tendon common to the RF,
      whereas VMdfs were attached directly to the medial aspect of the patella.
      Furthermore, the VMpfs were more active (P < .05) than VMdfs during maximum knee
      extensions. CONCLUSION: The anatomy, motor points, and electromyography clearly
      support an important distinction between the VMpfs and VMdfs. The role of the
      VMpfs would be one of assisting the RF in knee extension, whereas the VMdfs would
      track the patella medially without participating in knee extension. Because of
      these anatomical and functional differences, the VMpfs and VMdfs should be
      addressed very differently during quadriceps rehabilitation in patellofemoral
      dysfunctions.

PMID- 16461175
TI  - Validity of infrared thermal measurements of segmental paraspinal skin surface
      temperature.
AB  - OBJECTIVE: The purpose of this study was to evaluate the validity of thermal
      measurements by infrared camera thermometry. METHODS: Seventeen subjects
      underwent a 30-minute acclimatizing period in a controlled environment room.
      Thermal recordings were executed at the levels of C4 and L4. Fifteen recordings
      per segment were acquired in an alternating mode that always started at L4. Each
      subject was required to participate on 5 occasions. The exclusion criteria for
      the subjects included the following: no inflammatory disease or fever, no
      consumption of beverages containing caffeine, and no participation in physical
      activity 2 hours before the recording session; female subjects could not be
      menstruating on a day of recording. RESULTS: A total of 2550 recordings for the
      cervical area and the lumbar area was recorded. Strong significant correlations
      were found for the left (r = .77) and right (r = .71) lumbar sections (P < .0001)
      whereas weaker significant correlations were observed for the left (r = .56) and
      right (r = .63) cervical areas (P < .0001). The limits of agreement (Bland
      Altman) showed good relationships but poor interchangeability. CONCLUSIONS: In
      this study, the infrared cameras showed that they were valid tools in a
      controlled environment; however, the technique for the cervical measurements
      needs to be reassessed.

PMID- 16461176
TI  - Immunization and the chiropractor-patient interaction: a Western canadian study.
AB  - OBJECTIVE: To explore how the topic of vaccination arises during interactions
      between chiropractors and their patients, the advice that is given to patients,
      and the factors that influence the opinions of the chiropractors. METHODS: Data
      were collected in semistructured interviews with a purposeful sample of
      chiropractors in Calgary, Canada. Data were analyzed using qualitative content
      analysis and constant comparison. Participants were chiropractors who had
      participated in a postal survey of immunization-related beliefs and behaviors and
      who consented to contact for further study. RESULTS: Data redundancy was attained
      after 14 interviews were complete. Immunization arose in clinical encounters by
      both indirect (provision of reference materials and/or posting of media stories
      in clinic waiting rooms) and direct communication. Direct communications were
      most commonly patient initiated and were prompted by media reports, clinic
      waiting room material, or patient perceived adverse reactions; however, they were
      also initiated by the chiropractors, particularly if they were seeing young
      children with their parents. For some chiropractors, the emphasis was on
      providing information of a negative, antivaccination nature; others referred
      clients to physicians and nurses. Factors that influenced their opinions included
      their chiropractic training, philosophy of health and illness, and self or
      important others having experienced negative reactions that were perceived to
      result from immunization. CONCLUSIONS: Both patients and chiropractors initiate
      discussions on immunization in practice, with many chiropractors using indirect
      stimuli to open the topic. Doctors of chiropractic in this particular sample were
      heterogeneous with respect to the information provided to patients. However,
      study findings may not be generalizable outside Canada.

PMID- 16461177
TI  - The efficiency of multiple impulse therapy for musculoskeletal complaints.
AB  - OBJECTIVE: The aim of the study was to document the response of patients to
      multiple impulse therapy for a variety of musculoskeletal complaints encountered
      in clinical practice. METHODS: A single practitioner in a private clinic setting
      provided the therapy to 249 patients. Survival analysis was used to plot
      probability of pain vs the days required for symptom resolution for each of 8
      patient complaints. Analysis of variance was used to examine the influence of
      covariates such as age, sex, body mass index, and chronicity. RESULTS: The
      average number of visits required to achieve a pain-free state for each of 8
      patient symptoms, the half-life for response to multiple impulse therapy, and
      comparison of the results of published studies of low back and neck pain are
      presented. CONCLUSION: Response of patients in the study sample to multiple
      impulse therapy for symptoms of low back and neck pain appeared to be
      considerably faster than that obtained in 3 recent studies.

PMID- 16461178
TI  - Trunk-strengthening exercises for chronic low back pain: a systematic review.
AB  - OBJECTIVE: The objective of this systematic review was to determine the effect of
      lumbar spine-strengthening exercises on outcomes for people with chronic low back
      pain. METHODS: Two independent reviewers followed Cochrane Back Review Group and
      QUORUM Statement guidelines to complete this systematic review. Exercise effects
      were reported as standardized mean difference (SMD) with 95% confidence
      intervals. RESULTS: Thirteen high-quality randomized controlled trials were
      included. For chronic low back pain, trunk strengthening is more effective than
      no exercise on long-term pain (SMD 0.95 [0.35-1.55]; intensive trunk
      strengthening is more effective than less intensive on function (pooled SMD:
      short-term, 0.58 [0.22-0.94]; long-term, 0.77 [0.33-1.20]). Compared with
      physiotherapy or aerobics, effects are comparable on pain and function.
      Motivation strategies increase effectiveness. After disk surgery, effects are
      significant for function (pooled SMD: short-term, 1.08 (0.76-1.41); long-term,
      0.53 (0.03-1.04). For severe degeneration, trunk strengthening is less favorable
      than fusion on long-term pain (SMD, -0.50 [-0.99 to -0.01]) or function (SMD, 
      0.76 [-1.25 to -0.26]). Intensive trunk strengthening is less effective than
      McKenzie exercises for pain reduction (SMD: short-term, -0.29 [-0.54 to -0.05];
      long-term, -0.31 [-0.55 to -0.06]). We estimated that moderate effect sizes (0.5)
      indicate that approximately 50% of participants and large effect sizes (0.8)
      indicate that approximately 80% of participants would achieve important
      improvement. CONCLUSIONS: Trunk strengthening appears effective compared with no
      exercise. Increasing exercise intensity and adding motivation increase treatment
      effects. Trunk strengthening, compared with aerobics or McKenzie exercises,
      showed no clear benefit of strengthening. It is unclear whether observed benefits
      are due to tissue loading or movement repetition.

PMID- 16461179
TI  - Retropharyngeal abscess presenting as benign neck pain.
AB  - OBJECTIVE: To present a case of an uncommon presentation of cellulitis of the
      neck as benign neck pain. CLINICAL FEATURES: A 44-year-old man had severe neck
      pain and headaches for 2 weeks with an unknown cause. Minimal response to
      chiropractic treatment leads to coordination of treatment with the patient's
      primary care physician. Laboratory assessment and magnetic resonance imaging
      initially were viewed as insignificant but were repeated and showed a
      retropharyngeal abscess. INTERVENTION AND OUTCOME: Chiropractic treatment did not
      reduce the patient's neck pain as expected. Fusion of C1 to C2 was eventually
      performed. CONCLUSION: Neck pain is a common reason for patients to seek
      chiropractic care. This case shows an uncommon differential diagnosis for a
      patient who does not respond quickly to chiropractic treatment for neck pain.

PMID- 16461180
TI  - The Bournemouth Questionnaire: can it be used to monitor and predict treatment
      outcome in chiropractic patients with persistent low back pain?

PMID- 16461181
TI  - Role of outcome trials in providing information on antihypertensive treatment:
      importance and limitations.

PMID- 16461182
TI  - The X-cellent Study.

PMID- 16461183
TI  - Cardiac consequences of aldosterone excess in human hypertension.

PMID- 16461184
TI  - Role of aldosterone in left ventricular hypertrophy in hypertension.
AB  - BACKGROUND: Aldosterone induces cardiac fibrosis in experimental animal models,
      but only limited information is available on the association between aldosterone
      and left ventricular (LV) hypertrophy in human beings. The aim of the present
      study was to determine the role of aldosterone in LV geometry and to investigate
      other types of target organ damage in hypertensive patients. METHODS: A total of
      25 patients with primary aldosteronism caused by Conn's adenoma, 29 patients with
      renovascular hypertension, and 29 patients with essential hypertension (EHT) were
      included in the present study. Echocardiographic examinations and 24-h ambulatory
      blood pressure (BP) monitoring were conducted in all subjects. RESULTS: The mean
      24-h systolic and diastolic BP in primary aldosteronism and renovascular
      hypertension were found to be comparable to those in EHT. However, LV mass index
      adjusted by age, sex, mean 24-h systolic BP, mean 24-h pulse rate, body mass
      index, and duration of hypertension was significantly increased in the patients
      with primary aldosteronism and renovascular hypertension compared with values in
      patients with EHT (150.2 +/- 7.7, 142.3 +/- 7.2, and 115.2 +/- 7.2 g/m(2),
      respectively). Hypertensive organ damages, such as proteinuria and hypertensive
      retinopathy, were more pronounced in the patients with renovascular hypertension;
      however, LV hypertrophy was especially exaggerated in patients with primary
      aldosteronism. CONCLUSIONS: These results indicate that aldosterone may induce LV
      hypertrophy in human beings as well as in experimental animals, and that
      angiotensin II and aldosterone may differentially participate in causing
      hypertensive target organ damage.

PMID- 16461185
TI  - Aldosterone and left ventricular hypertrophy in Afro-Caribbean subjects with low
      renin hypertension.
AB  - BACKGROUND: Activity of the renin-angiotensin-aldosterone system is thought to
      play a major role in determining blood pressure (BP) and target organ damage such
      as left ventricular hypertrophy. In Afro-Caribbean subjects, however,
      hypertension tends to be more severe despite lower plasma renin activity. We
      investigated whether this might be due to a different relation between
      aldosterone and renin in Afro-Caribbean compared to white subjects. METHODS:
      Plasma aldosterone and renin activity were assessed in the morning after 15 min
      seated in 383 hypertensive subjects of Afro-Caribbean or white ethnicity (61%
      Afro-Caribbean, 83% on treatment) attending a hypertension clinic in London, UK.
      Left ventricular mass index (LVMI) was assessed by echocardiography in 276
      subjects. RESULTS: Plasma renin activity was lower in Afro-Caribbean compared to
      white subjects (0.4 [0.3-1.0] v 1.4 [0.5-3.4] ng/mL/h, medians [interquartile
      range], P < .0001). Despite this, aldosterone was higher in Afro-Caribbean
      compared to white subjects (8.0 [6.1-12.6] v 7.4 [2.3-17.1] ng/dL, medians
      [interquartile range], P < .01). The LVMI corrected for sex and BP was higher in
      Afro-Caribbean than in white subjects. In Afro-Caribbean but not in white
      subjects LVMI was independently correlated with plasma aldosterone (standardized
      regression coefficient, beta= 0.25, P < .001). CONCLUSIONS: In Afro-Caribbean
      hypertensive subjects in London, plasma aldosterone is elevated despite lower
      renin and may contribute to increased severity of hypertension and left
      ventricular hypertrophy in Afro-Caribbean compared to white subjects.

PMID- 16461186
TI  - Too much aldosterone--more common than we ever realized?

PMID- 16461187
TI  - Enhanced radial late systolic pressure augmentation in hypertensive patients with
      left ventricular hypertrophy.
AB  - BACKGROUND: Wave reflection augments central blood pressure (BP) in late systole,
      thus increasing cardiac afterload. We examined the relationship between late
      systolic pressure augmentation in the peripheral radial artery pulse wave and the
      existence of left ventricular hypertrophy (LVH) in hypertension. METHODS:
      Brachial BP, radial augmentation index (AI(r)), and carotid-femoral pulse wave
      velocity (PWV(cf)) were determined in 77 untreated hypertensive patients aged 56
      +/- 10 years. Cardiac structure and function were assessed by ultrasound, and LVH
      was defined based on the LV mass index (LVMI). Using multivariate analysis,
      patient characteristics were compared between those with (+) and without (-) LVH.
      RESULTS: The LVMI was correlated independently and positively with AI(r) (beta =
      0.33, P = .004) and the brachial mean arterial pressure (MAP; beta = 0.25, P =
      .03). The ratio of early to atrial peak velocities (E/A ratio) of the diastolic
      transmitral flow tended to be correlated negatively with the AI(r). The LVH (+)
      group had a significantly higher AI(r) than the LVH (-) group [LVH (+), 97% v LVH
      (-), 89%, P = .003]; this difference remained significant even after adjustment
      for age, gender, MAP, and heart rate. The adjusted relative risk of LVH was 1.99
      for each 10% AI(r) increase (P = .005). In contrast, LVMI was not correlated with
      the PWV(cf), and the PWV(cf) was not different between the LVH (+) and LVH (-)
      groups. Moreover, there was no significant correlation between PWV(cf) and AI(r).
      CONCLUSIONS: These results suggest that the peripheral AI(r) measurement is
      clinically useful in predicting LVH. Enhanced wave reflection may be related to
      the development of LVH in hypertensive patients.

PMID- 16461188
TI  - Expression of glucose transporter-1 and aquaporin-4 in the cerebral cortex of
      stroke-prone spontaneously hypertensive rats in relation to the blood-brain
      barrier function.
AB  - BACKGROUND: Cerebral edema is an important initial event in cases of stroke among
      humans. Although hypertension is a major risk factor for endothelial injury, the
      precise mechanisms regulating brain microvascular changes are still unknown. To
      elucidate the pathogenesis of increases in vascular permeability in the cerebral
      cortex, we investigated the expression of glucose transporter-1 (GLUT-1) in
      endothelial cells and aquaporin-4 (AQP4) in astrocytes in relation to blood-brain
      barrier (BBB) function. METHODS: Using male stroke-prone spontaneously
      hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY), the
      particular localization of both GLUT-1 and AQP4 was investigated by
      immunohistochemistry. Quantitative changes in these molecules were examined by
      Western blot analysis in these rats at 6 weeks and 20 weeks of age. Furthermore,
      to investigate the expression of these molecules at the mRNA level, reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis was carried out using
      20-week-old SHRSP and age-matched WKY. RESULTS: We confirmed the localization of
      GLUT-1 in endothelial cells and that of AQP4 in the end feet of astrocytes around
      microvessels, as determined by electron immunohistochemistry. No significant
      differences were found in the expression of these molecules in rats at 6 weeks of
      age, whereas GLUT-1 expression was lower, but that of AQP4 was higher, in SHRSP
      after the establishment of hypertension. Furthermore, GLUT-1 mRNA expression was
      lower in SHRSP, and AQP4 mRNA expression was also lower in SHRSP than in WKY at
      20 weeks of age. CONCLUSIONS: These results indicate that AQP4 may play a much
      more important role in BBB function than GLUT-1, and thereby also in water
      distribution in the cerebral cortex of SHRSP with severe hypertension.

PMID- 16461189
TI  - Reference values for SphygmoCor measurements in South Africans of African
      ancestry.
AB  - BACKGROUND: Measurements of blood pressure (BP) together with applanation
      tonometry at the radial and femoral arteries allow for reproducible assessments
      of various indexes of arterial stiffness, including peripheral (PP(p)) and
      central (PP(c)) pulse pressures, peripheral (AI(p)) and central (AI(c))
      augmentation indexes, and aortic pulse wave velocity (PWV). In the absence of an
      outcome-driven and ethnicity-specific reference frame, we defined preliminary
      diagnostic thresholds for subjects of African descent living in Africa, using the
      distributional characteristics of these hemodynamic measurements. METHODS: We
      randomly recruited 347 subjects from a South African population of African
      origins. The PP(p) was the average difference between systolic and diastolic BP
      measured five times consecutively at one home visit. For measurement of PP(c),
      AI(p), AI(c), and PWV, we used a high-fidelity micromanometer interfaced with a
      laptop computer running the SphygmoCor software. For analyses we selected 185
      subjects without hypertension, diabetes, and previous or concomitant
      cardiovascular disease. RESULTS: Mean age (33.5 years) was similar in 77 men and
      108 women. The PP(p), PP(c), AI(p), AI(c), and PWV significantly increased with
      age. The 95th prediction bands of this relation at age 30 years, approximated to
      70 mm Hg for PP(p), 50 mm Hg for PP(c), 100% for AI(p), 40% for AI(c), and 8.0
      m/sec for PWV. The aforementioned thresholds would need adjustment by
      approximately 2.5 mm Hg, 4.0 mm Hg, 10%, 6%, and 1.0 m/sec, respectively, for
      each decade that age differs from 30 years. CONCLUSIONS: Pending validation in
      prospective outcome-based studies 70 mm Hg for PP(p), 50 mm Hg for PP(c), 100%
      for AI(p), 40% for AI(c), and 8.0 m/sec might be considered as preliminary
      thresholds to diagnose increased arterial stiffness in young adult subjects of
      African descent.

PMID- 16461190
TI  - Effect of age on blood pressure parameters and risk of cardiovascular death in
      men.
AB  - BACKGROUND: Elevated blood pressure (BP) is a risk factor for cardiovascular
      disease (CVD), but it remains unclear which component-alone or in combination-is
      the best predictor. We sought to determine which BP parameters are important
      predictors of CVD death across a wide age range. METHODS: We used a prospective
      cohort study design with 53,163 men followed for cause-specific death during a
      median of 5.7 years in the Physicians' Health Study enrollment cohort. Baseline
      age, systolic BP and diastolic BP were collected. We calculated relative risks
      (RRs) and their 95% confidence intervals using Cox proportional hazard models
      adjusting for major risk factors for CVD, and then stratified by age (39 to 49,
      50 to 59, 60 to 69, and 70 to 84 years). RESULTS: There were 459 CVD deaths
      during follow-up. For each 10 mm Hg increase in systolic BP, the multivariable
      RRs by ascending age group were 1.46, 1.43, 1.24, and 1.13. The multivariable RRs
      for each 10 mm Hg increase in diastolic BP were 1.25, 1.20, 1.28, and 1.07.
      Compared with systolic BP, pulse pressure and mean arterial pressure were not
      consistent predictors across age ranges, and combining systolic BP with another
      parameter did not improve the model compared with using systolic BP alone in any
      age group (all P > .05). CONCLUSIONS: In this large cohort of healthy men with no
      history of hypertension, systolic BP was the most consistent and significant
      predictor of CVD death across all ages. Diastolic BP was not as strongly
      associated with risk. Our results support the continuing emphasis on using
      systolic BP in predicting cardiovascular risk.

PMID- 16461191
TI  - Prevalence, awareness, treatment and control of hypertension in Hellas, Greece:
      the Hypertension Study in General Practice in Hellas (HYPERTENSHELL) national
      study.
AB  - BACKGROUND: The Hypertension Study in General Practice in Hellas (Hypertenshell)
      is a cross-sectional study (much like the National Health and Nutrition
      Examination Study) for assessing the prevalence, level of awareness, treatment,
      and control of hypertension in Greece. METHODS: The study was conducted with the
      collaboration of physicians in 98 Health Centers across Greece. Participants were
      interviewed about lifestyle, and blood pressure (BP) measurements were taken on
      two clinical visits for verification of diagnosis and control of hypertension.
      Hypertension was defined as systolic BP > or =140 mm Hg or diastolic BP > or =90
      mm Hg, or current treatment with antihypertensive drugs; the same threshold was
      used for assessing control of hypertension. RESULTS: A total of 11,950
      individuals participated and data for 11,540 were analyzed, comprising 0.1% of
      the Greek population. The prevalence of hypertension was 31.1% (men 33.6%, women
      28.4%); among elderly individuals (>65 years) the prevalence was higher (65.4%).
      Of the hypertensive individuals, 39.8% did not know that had hypertension,
      yielding an awareness of 60.2%; in addition, 12.4% were aware but not treated
      (men 13.1%, women 11.8%). In all, 51.2% (1838) of hypertensive subjects were
      treated; 67.2% (1235) were treated but not controlled (men 66.7%, women 67.7%);
      and 32.8% (603) were treated and controlled (men 33.3%, women 32.3%).
      CONCLUSIONS: The results of the Hypertenshell Study indicate that hypertension is
      a common risk factor for cardiovascular disease in the Greek population.
      Awareness, treatment, and control of hypertension are comparable to the best
      rates of control of hypertension given for the problem, but there is a
      considerable potential for further improvement in the control of this disease.

PMID- 16461192
TI  - The G protein-coupled receptor kinase 4 gene affects blood pressure in young
      normotensive twins.
AB  - BACKGROUND: G protein-coupled receptor kinase 4 (GRK4) is involved in activity of
      dopamine receptors in renal proximal tubules and thus mediates sodium
      reabsorption and blood pressure (BP) regulation. The present study evaluated the
      impact of the GRK4 gene variants on BP levels in normotensive adolescents and
      young adults. METHODS: Three functional polymorphisms of R65L, A142V, and A486V
      were genotyped in 934 white and African American (44.2%) twin subjects (17.4 +/-
      3.4 years of age). A number of association approaches including single-locus
      analyses, haplotype trend regression analyses, and sib-pair transmission
      disequilibrium tests were carried out. RESULTS: Single-locus analyses revealed a
      significant interaction between R65L and age for SBP (P = .019) with an obvious
      gene-dose effect. In L65L homozygotes SBP showed the steepest increase with age
      (beta = 0.85, P = .003), R65L heterozygotes showed the next steepest increase
      (beta = 0.54, P < .001), and the effect of age on SBP was absent in R65R
      homozygotes. Stratified analyses showed that the SBP increasing effect of the 65L
      allele was significant only in the older group of subjects (114.1 +/- 11.1 mm Hg
      v 110.1 +/- 9.6 mm Hg, P = .024). Sib-pair transmission disequilibrium tests
      analyses in 72 informative dizygotic twin pairs confirmed the significant effect
      of the 65L on SBP; carriers of the 65L allele had a higher SBP compared with
      noncarriers (110.3 +/- 8.2 v 107.3 +/- 7.8 mm Hg, P = .047). Haplotype analyses
      uncovered an interaction between haplotype 65L-142V-486A and age for SBP (P =
      .017); individuals who were homozygous for haplotype 65L-142V-A486 showed a 1.05
      mm Hg steeper increase in SBP per year increase in age compared with those
      homozygous for the most common R65-A142-A486 haplotype. CONCLUSION: Our data
      indicate that the R65L polymorphism of the GRK4 gene plays a role in BP
      regulation in adolescents and young adults.

PMID- 16461193
TI  - Genetic variations in CC chemokine receptors and hypertension.
AB  - BACKGROUND: CC-chemokine receptor 5 (CCR5) is a co-receptor for human
      immunodeficiency virus type 1 (HIV-1) infection. Homozygosity for a 32-base pair
      (bp) deletion (Delta32) in the CCR5 gene confers resistance to HIV-1. Previous
      studies found an increased prevalence of hypertension among CCR5-Delta32
      homozygotes and among carriers of a polymorphism (CCR2-64I) found on the gene
      that codes a closely related chemokine receptor. The present study was carried
      out to verify these associations. METHODS: Subjects in this cross-sectional study
      were selected from the Global Repository at Genomics Collaborative, which
      includes patients and healthy control subjects enrolled at multiple clinical
      sites in the United States and other nations. The current study includes 2842
      subjects with hypertension and 2893 nonhypertensive control subjects from white
      populations in the United States and Poland. Case and control subjects were
      frequency matched by age, gender, and birthplace. All subjects were genotyped for
      CCR5-Delta32 and CCR2-64I polymorphisms by established Taqman assays. RESULTS:
      The CCR5-Delta32 genotype was not found to be associated with hypertension (CCR5
      Delta32 heterozygosity: odds ratio [OR] 0.99, 95% confidence interval [CI] 0.87
      to 1.14; CCR5-Delta32 homozygosity: OR 1.07, 95% CI 0.68 to 1.67) among these
      subjects. There was also no association between CCR2-64I genotype and
      hypertension (CCR2-64I heterozygosity: OR 0.96, 95% CI 0.83 to 1.10; CCR2-64I
      homozygosity: OR 1.18, 95% CI 0.73 to 1.92). These results changed little after
      adjustment for potential confounding variables. CONCLUSION: The results of the
      present study, which is much larger than previously published studies, provide no
      evidence that either CCR5-Delta32 or CCR2-64I is associated with hypertension.

PMID- 16461194
TI  - CCR polymorphisms and hypertension.

PMID- 16461195
TI  - Association between hypertension and primary mitral chordae tendinae rupture.
AB  - BACKGROUND: Mitral regurgitation from chordae tendinae rupture (CTR) may cause
      severe clinical symptoms and is a progressive disease that eventually results in
      the need for mitral valve surgery. Early recognition of CTR and identification of
      risk factors are important because early intervention increases the chances of
      survival. Hypertension may increase mitral valve complex mechanical strain and
      cause the chordae tendinae to rupture. METHOD: Using a cross-sectional study of
      medical files in one medical center in Taiwan, we enrolled 98 patients with
      mitral CTR and classified them into two groups, comprising 68 subjects (69%)
      without obvious predisposing factors (primary group) and 30 subjects (31%) with
      known predisposing causes (secondary group). RESULT: Of the subjects, 63 (64%)
      were men with a mean age of 57.5 +/- 1.5 years. The posterior mitral leaflet was
      most commonly involved (64%). The known predisposing factors in secondary group
      include mitral valve prolapse, infective endocarditis, and rheumatic heart
      disease. The patients who had primary CTR were older (59.9 +/- 1.6 v 52.1 +/- 3.1
      years, P = .029), had a higher prevalence of hypertension (56% v 30%, P = .018)
      and complained more often of dyspnea (82% v 53%, P = .003) than the patients in
      the secondary group. Using binary logistic regression analyses, the variation in
      primary group was found to be independently explained by age (P = .039, odds
      ratio = 1.039, 95% confidence interval = 1.002 to 1.077) and hypertension (P =
      .048, odds ratio = 2.717, 95% confidence interval = 1.008 to 7.326). CONCLUSION:
      We conclude that hypertension was an independent predictor for primary CTR in
      this study.

PMID- 16461196
TI  - Combination of exercise and enalapril enhances renoprotective and peripheral
      effects in rats with renal ablation.
AB  - BACKGROUND: It is suggested that appropriate chronic exercise (EX) may produce
      improvements of the physical strength in patients with chronic renal failure
      (CRF). Because acute exercise causes proteinuria and decreases the renal blood
      flow and glomerular filtration rate, it is necessary to consider the influence of
      EX on renal function. Therefore, we assessed the renal and peripheral effects of
      moderate to intense EX as well as the effects of the combination of EX and
      enalapril (ENA) in a rat model of CRF. METHODS: Male 5/6-nephrectomized Wistar
      Kyoto rats were divided into six groups according to the following treatment: 1)
      no exercise (C); 2) ENA (2 mg/kg/day, subcutaneously); 3) moderate exercise with
      treadmill running (20 m/min for 60 min/day, 5 days/week) (EXm); 4) intense
      exercise with treadmill running (28 m/min for 60 min/day, 5 days/week) (EXi); 5)
      EXm+ENA; and 6) sham operation (S). The rats were then treated for 12 weeks.
      RESULTS: Both EX and ENA blocked the development of hypertension, blunted
      increases in proteinuria, reduced serum creatinine and blood urea nitrogen, and
      improved the index of glomerular sclerosis (IGS) and the relative interstitial
      volume of the renal cortex (RIV). Moreover, IGS and RIV in the EXm+ENA group were
      the lowest among all other nephrectomized groups. Furthermore, EXm+ENA enhanced
      capillarization as well as the proportion of type-I fiber in the soleus muscle.
      CONCLUSIONS: These results suggest that EX and ENA have renoprotective effects.
      The findings also suggest that EXm+ENA provided greater renoprotective effects
      than those of ENA alone, and that EXm+ENA had some additional peripheral effects
      without any complications in this rat model.

PMID- 16461197
TI  - Increased levels of atherosclerosis markers in salt-sensitive hypertension.
AB  - BACKGROUND: Salt sensitivity in essential hypertension is associated with both
      endothelial dysfunction and increased cardiovascular risk. We evaluated several
      serum markers of atherosclerosis and endothelial function in a group of essential
      hypertensive patients classified on the basis of their salt sensitivity. METHODS:
      Forty-three patients were classified as having salt-sensitive (20 subjects) or
      salt-resistant (23 subjects) hypertension on the basis of their 24-h blood
      pressure (BP) response from low salt (50 mmol/d) to high salt (250 mmol/d)
      intake. Endothelium-dependent and independent responses were measured in the
      forearm previously to salt manipulation. High-sensitivity C-reactive protein
      (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular
      cell adhesion molecule type 1 (sVCAM-1), e-selectin, p-selectin, interleukin-6
      (IL-6), monocyte chemotactic protein type 1 (MCP-1), matrix metalloproteinases
      types 1, 2, and 9 (MMP-1, MMP-2, and MMP-9), and the tissue inhibitor of
      metalloproteinases type 1 (TIMP-1) were measured in serum on the last day of both
      low salt and high salt intakes. RESULTS: Compared to salt-resistant patients,
      salt-sensitive hypertensives showed age-adjusted increased levels of p-selectin
      (P = .006), e-selectin (P = .042), and MCP-1 (P = .036), although differences in
      e-selectin were not maintained after adjustment for BP values. Moreover, salt
      sensitive subjects exhibited decreased serum levels of MMP-9 (P = .007) and
      increased levels of TIMP-1 (P = .045). No differences in serum CRP, sICAM-1,
      sVCAM-1, or IL-6 were observed between salt-sensitive and salt-resistant
      patients. Finally, maximal acetylcholine-induced vasodilation (319% +/- 153% v
      414% +/- 178% increase in forearm blood flow; P = .022 age-adjusted) was
      significantly impaired in salt-sensitive hypertensives. CONCLUSIONS: Serum
      markers of inflammation, especially selectins and chemokines, as well as markers
      of vascular remodeling, and endothelium-dependent vasodilation are altered in
      salt-sensitive hypertension. These alterations could help to explain the greater
      target organ damage and cardiovascular risk observed in salt-sensitive subjects.

PMID- 16461198
TI  - Cardiovascular effects of hyperhomocysteinemia in conscious unrestrained rats.
AB  - BACKGROUND: Experiments were designed to determine whether hyperhomocysteinemia
      (Hhe) affects cardiovascular function when monitored in conscious unrestrained
      animals. METHODS: Adult, male Sprague-Dawley rats were fed a homocystine
      supplemented diet for 6 months. Blood pressure (BP), heart rate, and pulse
      pressure were monitored continuously, 24 h a day, using biotelemetry techniques.
      RESULTS: The resulting intermediate level of Hhe was not associated with
      significant changes in heart rate, diastolic BP, systolic BP, or the circadian
      variation in heart rate. In spite of the lack of significant changes in systolic
      and diastolic BP, there was a slight but statistically significant increase in
      pulse pressure after 4 months of treatment that returned toward control levels
      after 6 months. CONCLUSIONS: Current results indicate that Hhe alone does not
      have significant effects on BP. Furthermore, they suggest that the previously
      reported Hhe-induced adverse cardiac remodeling and diastolic dysfunction in this
      animal model are not the result of pressure overload.

PMID- 16461199
TI  - Deterioration of insulin sensitivity and glucose effectiveness with age and
      hypertension.
AB  - BACKGROUND: This study examined the relative role of age and hypertension in
      deterioration of insulin-dependent (insulin sensitivity, S(I)) and insulin
      independent (glucose effectiveness, S(G)) actions on glucose tolerance. METHODS:
      We applied the minimal model of glucose kinetics to estimate S(I) and S(G)
      indexes from insulinemia and glycemia data detected during a frequently sampled
      intravenous glucose tolerance test performed in 21 normoglycemic subjects who
      were not affected by the metabolic syndrome (MS): seven young normotensive
      subjects (YN; mean age 29.3 +/- 1.5 years), six elderly normotensive subjects
      (EN; mean age 57.0 +/- 3.4 years) and eight elderly hypertensive patients (EH;
      mean age 62.1 +/- 2.1 years). RESULTS: Both normotensive subject groups (YN and
      EN) showed no significant difference in S(I) estimates despite significantly
      different age, whereas a significant reduction was evident in the EH patients
      compared with these groups. Mean estimates of S(G) showed no significant
      difference in elderly subject groups (EN and EH), irrespective of hypertension,
      whereas a significant increase was evident in the YN (analysis of variance
      followed by Scheffe test, P < .05). CONCLUSIONS: Our study demonstrates that, in
      the absence of MS: 1) insulin sensitivity in normotensive subjects is independent
      of age; b) hypertension is associated with insulin resistance in elderly
      subjects; and c) age is a primary predictor of deterioration in glucose
      effectiveness, independent of hypertension.

PMID- 16461200
TI  - Insulin sensitivity and glucose resistance in elderly hypertensive patients.

PMID- 16461201
TI  - A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to
      moderate hypertension using ambulatory blood pressure monitoring.
AB  - BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that
      is associated with an increased risk of acute coronary and cerebrovascular
      events. In a prospective, randomized, open-label, blinded-endpoint, parallel
      group, multicenter, forced-titration study of telmisartan and ramipril, the
      efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP
      (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After
      screening and a single-blind run-in phase, 812 adults with mild-to-moderate
      hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and
      a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14
      week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80
      mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the
      morning. The primary efficacy variable was change from baseline in the last 6-h
      mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring
      (ABPM). Secondary efficacy variables were changes from baseline in BP control
      during each of the 24-h periods and in-clinic trough cuff BP. RESULTS:
      Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline
      in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001),
      respectively. At 14 weeks, the adjusted mean change from baseline in DBP for
      telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm
      Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan
      80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P <
      .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from
      baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8
      mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P <
      .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10
      mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night
      time, and morning periods. Treatment-related adverse events were uncommon;
      patients treated with ramipril had a higher incidence of cough than those treated
      with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was
      consistently more effective than ramipril 10 mg in reducing both DBP and SBP
      during the last 6 h of the dosing interval, a measure of the early morning period
      when patients are at greatest risk of life-threatening cardiovascular and
      cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril
      10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were
      well tolerated.

PMID- 16461202
TI  - Indapamide SR versus candesartan and amlodipine in hypertension: the X-CELLENT
      Study.
AB  - BACKGROUND: Reducing systolic blood pressure (BP) is of major benefit to patients
      with isolated systolic hypertension, but lowering normal diastolic BP may be
      harmful in terms of cardiovascular risk. Effects of different drugs on systolic
      BP, diastolic BP, and pulse pressure are therefore of interest. METHODS: The
      NatriliX SR versus CandEsartan and amLodipine in the reduction of systoLic blood
      prEssure in hyperteNsive patienTs study (X-CELLENT) was a randomized, double
      blind, placebo-controlled study comparing the effects of three drugs on these BP
      components. Patients with systolic-diastolic or isolated systolic hypertension (n
      = 1758) received indapamide (1.5 mg) sustained release (SR), candesartan (8 mg),
      amlodipine (5 mg), or placebo once daily for 12 weeks. RESULTS: Compared to
      placebo all active treatments reduced all BP components significantly (P < .001).
      For the patients with isolated systolic hypertension (n = 388), the three
      treatments significantly reduced systolic BP, but only indapamide SR did not
      change diastolic BP and thus reduced pulse pressure significantly relative to
      placebo (P = .005). In an ancillary study using ambulatory BP monitoring (n =
      576), all three treatments significantly reduced BP components during 24 h
      relative to placebo. Changes in systolic BP and pulse pressure were similar with
      the three treatments, but the reduction in diastolic BP was significantly
      smaller, and therefore more favorable, with indapamide SR compared with
      candesartan (P = .039). In patients with isolated systolic hypertension (n =
      106), indapamide SR reduced 24-h systolic BP significantly more than amlodipine
      (P = .037), and only indapamide SR reduced 24-h pulse pressure significantly
      relative to placebo (P = .03). All three drugs were well tolerated. CONCLUSIONS:
      This distinctive BP-lowering profile of indapamide SR seems highly beneficial
      when compared to the either of candesartan or amlodipine.

PMID- 16461204
TI  - Provocative sacroiliac joint maneuvers and sacroiliac joint block are unreliable
      for diagnosing sacroiliac joint pain.
AB  - Mapping studies of pain elicited by injections into the sacroiliac joints (SIJs)
      suggest that sacroiliac joint syndrome (SIJS) may manifest as low back pain,
      sciatica, or trochanteric pain. Neither patient-reported symptoms nor provocative
      SIJ maneuvers are sensitive or specific for SIJS when SIJ block is used as the
      diagnostic gold standard. This has led to increasing diagnostic use of SIJ block,
      a procedure in which an anesthetic is injected into the joint under arthrographic
      guidance. However, several arguments cast doubt on the validity of SIJ block as a
      diagnostic gold standard. Thus, the effects of two consecutive blocks are
      identical in only 60% of cases, and the anesthetic diffuses out of the joint in
      61% of cases, often coming into contact with the sheaths of the adjacent nerve
      trunks or roots, including the lumbosacral trunk (which may contribute to pain in
      the groin or thigh) and the L5 and S1 nerve roots. These data partly explain the
      limited specificity of SIJ block for the diagnosis of SIJS and the discordance
      between the pain elicited by the arthrography injection and the response to the
      block. The limitations of provocative maneuvers and SIJ blocks may stem in part
      from a contribution of extraarticular ligaments to the genesis of pain believed
      to originate within the SIJs. These ligaments include the expansion of the
      iliolumbar ligaments, the dorsal and ventral sacroiliac ligaments, the
      sacrospinous ligaments, and the sacrotuberous ligaments (sacroiliac joint lato
      sensu). They play a role in locking or in allowing motion of the SIJs.
      Glucocorticoids may diffuse better than anesthetics within these ligaments.
      Furthermore, joint fusion may result in ligament unloading.

PMID- 16461203
TI  - An updated meta-analysis of genome scans for hypertension and blood pressure in
      the NHLBI Family Blood Pressure Program (FBPP).
AB  - A meta-analysis of the results from a multicenter genome-wide linkage study for
      hypertension and blood pressure (BP) based on an initial sample of 6,245
      individuals was published in 2003. We report here a combined linkage analysis of
      hypertension and BP using the complete Family Blood Pressure Program (FBPP)
      dataset, which includes a total of 12,028 genotyped individuals. Genome-wide
      linkage analyses for hypertension and BP were first performed in each of the
      studied ethnic group within each network and the results were combined with a
      meta-analysis using a modified Fisher's method of combining P values. Our meta
      analysis of genome scans for the latest FBPP dataset reveals suggestive linkage
      for hypertension and BP at several regions on the human genome. Strong evidence
      for linkage at two of these regions, 2p14 and 3p14.1, have also been published in
      previous meta-analyses, making them good candidate locations for susceptibility
      variants.

PMID- 16461205
TI  - Osteoarticular side effects of BCG therapy.
AB  - Although osteoarticular side effects of the Bacillus Calmette-Guerin (BCG) are
      rare compared to the number of administrations, BCG vaccination and cancer
      therapy are so widely used that the absolute number of cases is not negligible.
      Osteoarticular infection is an exceedingly rare complication of vaccination with
      the BCG. Intravesical BCG instillations used to treat superficial bladder cancer
      may cause arthralgia, reactive arthritis or osteoarticular infections.
      Intradermal BCG therapy used to treat a number of malignancies can cause
      osteoarticular infections or bilateral symmetric polyarthritis predominating in
      the wrists and fingers. In practice, when intravesical BCG instillation is
      followed by arthritis, hyperthermia is unhelpful for distinguishing septic
      arthritis from reactive arthritis. Arguments pointing to reactive arthritis
      include oligo- or polyarticular involvement and onset a few weeks (as opposed to
      a few months) after the last instillation. Nevertheless, joint fluid examination
      is in order to rule out septic arthritis. BCG-induced reactive arthritis usually
      responds well to nonsteroidal anti-inflammatory drugs. Osteoarticular infections
      related to BCG therapy should be treated by rifampin, isoniazid and ethambutol
      for 2 months, followed by rifampin and isoniazid for 10 months.

PMID- 16461206
TI  - Spinal muscle evaluation using the Sorensen test: a critical appraisal of the
      literature.
AB  - The first test for evaluating the isometric endurance of trunk extensor muscles
      was described by Hansen in 1964. In 1984, following a study by Biering-Sorensen,
      this test became known as the "Sorensen test" and gained considerable popularity
      as a tool reported to predict low back pain within the next year in males. The
      test consists in measuring the amount of time a person can hold the unsupported
      upper body in a horizontal prone position with the lower body fixed to the
      examining table. This test has been used in many studies, either in its original
      version or as variants. Although its discriminative validity, reproducibility,
      and safety seem good, debate continues to surround its ability to predict low
      back pain; in addition, the gender-related difference in position-holding time
      remains unexplained and the influence of body weight unclear. A contribution of
      the hip extensor muscles to position holding has been established, but its
      magnitude remains unknown. The influence of personal factors such as motivation
      complicates the interpretation of the results. Despite these drawbacks, the
      Sorensen test has become the tool of reference for evaluating muscle performance
      in patients with low back pain, most notably before and after rehabilitation
      programs.

PMID- 16461207
TI  - Characteristics of joint degeneration in hand osteoarthritis.
AB  - OBJECTIVES: To assess quantitatively the relative contribution of joint
      degeneration characteristics such as osteophytes (OS), joint space narrowing
      (JS), subchondral sclerosis (SS), subchondral cysts (SC), lateral deformity (LD)
      and cortical collapse (CC) to the Kellgren and Lawrence (K-L) score grade of hand
      osteoarthritis (OA). METHODS: Radiographs of both hands were taken from 1245
      study participants, native Chuvasha, Russian Federation. K-L score and the six
      above-mentioned characteristics were assessed on 15 joints of each hand. Multiple
      regression and correlation analyses were performed: for rows of hand joints and
      groups of thumb joints, and for the aforementioned rows but assigned into six age
      groups. RESULTS AND CONCLUSIONS: According to the K-L grading system the relative
      contribution of OS to joint degeneration was high in all stages of the process.
      JS and SS played an important role in determining the K-L score in persons
      younger than 40 but less so in older people. Conversely, influence of SC and LD
      is insignificant at the onset of OA (i.e., in young persons), yet in older people
      it was a leading determinant of the K-L score. CC exerts no influence on the K-L
      score of OA.

PMID- 16461208
TI  - Worldwide epidemiology of HBV infection, disease burden, and vaccine prevention.
AB  - Worldwide, hepatitis B virus (HBV) is the most common among those hepatitis
      viruses that cause chronic infections of the liver in humans, and it represents a
      global public health problem. Chronic hepatitis caused by HBV is the major cause
      of hepatocellular carcinoma (HCC) worldwide, and remains therefore a major public
      health problem globally. This fact is related to both the continuing occurrence
      of frequent new infections and to the presence of a large reservoir of persons
      chronically infected, which may develop severe and fatal complications of chronic
      liver disease. Hepatitis B and all of the complications resulting from it, as
      well hepatitis D (HDV) and its complications, are globally preventable by
      hepatitis B vaccination, and therefore elimination of HBV transmission and of new
      acute and chronic infections is a feasible goal.

PMID- 16461209
TI  - Therapeutic vaccination against chronic hepatitis B virus infection.
AB  - Chronic liver disease and hepatocellular carcinoma due to chronic hepatitis B
      virus (HBV) infection pose a major public health problem in highly endemic
      regions. Effective vaccines against HBV exist but more than 370 million people
      remain chronically infected with HBV For these patients there is a high risk to
      develop cirrhosis and hepatocellular carcinoma. Currently available therapies
      fail to control viral replication in the long term in most patients. Viral
      persistence has been associated with a defect in the development of HBV specific
      cellular immunity. Strategies to boost or to broaden the weak virus-specific T
      cell response of patients with chronic hepatitis B have been proposed as a means
      of curing this persistent infection. HBV envelope- and nucleocapsid-based
      vaccines, new formulations for recombinant vaccines and DNA-based vaccines are
      currently being assessed in clinical trials. Improvements are clearly required,
      but vaccination is likely to be the cheapest and potentially most beneficial
      treatment.

PMID- 16461210
TI  - The current status of antiviral therapy of chronic hepatitis B.
AB  - In recent years, marked progress has been made in the treatment of chronic viral
      hepatitis. Recent studies suggest that pegylated interferons (PEG IFNs) are more
      effective than standard IFNs in the treatment of chronic hepatitis B. So far, the
      combination of PEG IFN with lamivudine, used simultaneously, is disappointing in
      terms of short-term efficacy. However, long-term efficacy needs to be addressed
      and different schedules of combination, for example sequential, need to be
      evaluated. A number of nucleoside analogues, with favourable toxicity profiles
      and a promise of increased effectiveness against HBV, are in various stages of
      clinical development. Entecavir has recently been approved in the USA. The future
      of chronic hepatitis B therapy seems to be in the combination of different drugs.
      Ideally, the optimal drugs to combine would meet the following criteria: they
      should have a potent antiviral effect, an excellent safety profile and the
      duration of therapy should be limited. Indeed, the concept of combination therapy
      has been recently developed in order to increase efficacy and to decrease the
      occurrence of viral resistance. However, so far there are few data available and
      no combination therapy demonstrated a clear benefit as compared with monotherapy.
      More potent drugs and new combinations together with the understanding of the
      mechanisms of resistance to therapy are challenges to improve the efficacy of
      treatment and decrease in the future the global burden related to chronic
      hepatitis B.

PMID- 16461211
TI  - The concept of hepatitis B virus mutant escape.
AB  - Hepatitis B virus (HBV) reverse transcriptase is an error-prone enzyme, and this
      results in a large number of nucleotide substitutions during replication. As a
      result, HBV has a "quasispecies" distribution in infected individuals, meaning
      that HBV circulates as a complex mixture of genetically distinct but closely
      related variants that are in equilibrium at a given time point of infection in a
      given replicative environment. The quasispecies distribution of HBV implies that
      any newly generated mutation conferring a selective advantage to the virus in a
      given replicative environment will allow the corresponding viral population to
      overtake the other variants. Such selection processes occur at any step of
      infection to allow the emergence of variant viruses, such as precore and core
      promoter mutants during the natural course of infection, HBs antigen mutants
      under the pressure of active or passive anti-HBs immunization, or HBV mutants
      that are resistant to the antiviral action of specific HBV inhibitors.

PMID- 16461212
TI  - Molecular epidemiology of hepatitis B in England and Wales.
AB  - This review focuses on general and molecular features of the epidemiology of
      incident and prevalent hepatitis B virus (HBV) infections in England and Wales.
      The situation in Scotland and Northern Ireland will not be reviewed.

PMID- 16461213
TI  - HBV epidemiology in Latin America.
AB  - In Latin America, despite the paucity of population studies, hepatitis B is
      considered endemic. The western Amazonia is a highly endemic area where hepatitis
      D is also prevalent. In this area, outbreaks of fulminant hepatitis due to H13V
      and HDV are frequently reported. Non-safe sexual activity seems to be the most
      important transmission route, but intrafamilial transmission, during early
      childhood, is extremely significant in Amazonia. The H13V genotype distribution
      is heterogeneous with a high prevalence of genotype F in the Amazonian region and
      genotype A in all other areas. In the region where Asian and Italian immigration
      occurred, genotypes B, C and D are also described.

PMID- 16461214
TI  - Mechanism of HBV genome variability and replication of HBV mutants.
AB  - Naturally occurring mutations in the H13V genome have been extensively
      documented, yet the biological consequences of even the dominant mutations have
      not been well characterized. In a recent study of HBeAg-positive French patients
      infected with genotype A, we obtained full-length clones with high or low
      replication capacities in the transfected human hepatoma cells. Surprisingly,
      high replicating clones were all derived from low viremia samples, and harbored
      core promoter mutations. The highest replicating clones all contained point
      mutations in addition to those at 1762/1764, and site-directed mutagenesis
      confirmed their role in further enhancing genome replication and suppressing
      HBeAg expression. Several core promoter mutants were defective in virion
      secretion, and mapping experiments revealed three missense mutations in the small
      envelope protein to be responsible: I110M, G119E, and R169P The effect of I110M
      and G119E mutations can be relieved by another point mutation that creates a
      novel N-linked glycosylation site. Finally, the African/Asian subgroup of
      genotype A (genotype Aa) contains unique mutations and is associated with low
      viremia titers as well as low HBeAg prevalence. We found point mutations upstream
      of the precore ATG codon of genotype Aa suppressed HBeAg expression, while the
      G1862T mutation in the precore region greatly impaired viral replication. Thus,
      molecular characterization can shed light on viral properties associated with
      clinical infection.

PMID- 16461215
TI  - The natural history of chronic hepatitis B virus infection.
AB  - Under most circumstances, HBV is not cytopathic and it is the immune response of
      the host that determines the outcome of infection. The most complete immune
      response is associated with the most severe liver injury and the greatest
      likelihood of viral clearance, whereas an immature immune response leads to
      chronic hepatitis. The natural history of chronic hepatitis B is similar to that
      of acute HBV infection except for the different time frame, and can be viewed in
      four stages. The first stage is characterized by high viral loads and immune
      tolerance. In acute infection, this corresponds to the incubation period, but
      with neonatal chronic infection, this period often lasts for decades. In the
      second stage, an immunologic response develops leading to hepatocyte necrosis. In
      patients with chronic infection, stage 2 may persist for 10-20 years and lead to
      cirrhosis and its complications. When the immune response decreases the number of
      infected cells, a third stage begins with low viral replication, referred to as
      the inactive carrier state. In this stage, HBeAg is no longer detectable, a
      marked decrease in HBV viral load is observed, and aminotransferase levels become
      normal. During stage 3, some patients continue to have high levels of serum HBV
      DNA and amino-transferases (referred to as HBeAg-negative chronic hepatitis),
      because of HBV variants that prevent the production of HBeAg. In the fourth
      stage, patients become negative for HBeAg and positive for anti-HBs, and HBV DNA
      is usually no longer detectable in serum, although still present in liver tissue.
      Immune clearance occurs at a rate of about 1% per year in chronic carriers of HBV
      During stage 4, some patients can reactivate their hepatitis B when given
      chemotherapy or immuno-suppressive treatment. Patients with active HBV
      replication are at increased risk for cirrhosis, hepatic decompensation and
      hepatocellular carcinoma compared to inactive carriers. Available evidence
      indicates that control of HBV replication with antiviral agents decreases the
      incidence of these complications.

PMID- 16461216
TI  - The current management of HBV drug resistance.
AB  - Lamivudine and adefovir have potent inhibitory effects on hepatitis B virus (HBV)
      replication. Although short-term therapy is feasible in a selected subgroup of
      patients, prolonged therapy is required for sustained suppression in the majority
      of patients. However, HBV species with mutations in the tyrosine-methionine
      aspartate-aspartate (YMDD) locus of the HBV RNA-dependent DNA polymerase (rtM204
      I/V) conferring resistance to lamivudine may emerge after 9-10 months therapy.
      The incidence increases with duration of therapy up to 70% after 5 years
      lamivudine therapy. Serum alanine aminotransferase (ALT) elevation and HBV DNA
      rebound ( I log) occur in >90% of the patients with rtM204 I/V during continued
      lamivudine therapy. Marked flare of serum ALT may occur, sometimes severe, and
      may be complicated with decompensation or even fatality. The initial clinical and
      histologic improvement may also reverse after emergence of rtM204 IN Studies do
      suggest that stopping seems better than continuing lamivudine therapy. Limited
      data show that interferon therapy seems ineffective. Add-on adefovir therapy is
      effective in suppressing rtM204 I/V in both compensated and decompensated
      patients. Switching to adefovir monotherapy is effective and safe even in
      cirrhotic patients with decompensation. The overall incidence of
      adefovirresistant rtN236T and A181V is low, being 0 after one year and 5.9% after
      3 years' therapy. The impact of adefovir resistance is less clear but is
      responsive to lamivudine therapy. In conclusion, monitoring of viral breakthrough
      to start effective intervention is mandatory during direct antiviral therapy.

PMID- 16461217
TI  - New targets and inhibitors of HBV replication to combat drug resistance.
AB  - All the approved chemotherapeutic drugs for the treatment of HBV hepatitis are
      nucleoside analogs targeting on HBV DNA polymerase. Drugs targeting on other
      viral unique targets are needed. A new class of chemicals with novel action
      against HBV replication was discovered. A brief description of their mode of
      action is given.

PMID- 16461218
TI  - Clinical impact of occult HBV infections.
AB  - HBV infection in the absence of HBsAg has been a matter of debate for years, but
      its existence and clinical relevance are now supported by many publications,
      editorials and reviews. HBV DNA without HBs antigenemia was detected in the
      following clinical situations: (1) Chronic, presumably viral, hepatitis unrelated
      to HCV, atypical alcoholic hepatitis and hepatocellular carcinoma (HCC); (2)
      viral reactivation following immunosuppression; (3) Transmission through
      transplantation, transfusion or experimental transmission to chimpanzees. Occult
      HBV infections are not restricted to areas of high HBV endemicity. Indeed, such
      cases have been described in Western countries including France. It is now
      established that occult HBV infection among non-HCV patients suffering from
      chronic hepatitis varies from 20% to 30% in Europe, and in the context of HCV
      infection it varies from 20% in France up to 80% in Japan. The percentage of
      occult HBV infections among non A-E cases depends on several parameters: (1) The
      method of detection, including PCR primer selection; (2) patient recruitment; (3)
      patients from countries highly endemic for HBV are more likely to develop occult
      HBV infections; (4) prevalence may also vary depending on the nature of
      biological material tested, with a higher proportion for liver compared to serum
      specimen. The mechanisms leading to HCC in occult HBV infection seem similar to
      those overt cases, patients with low-grade but diagnosable HBV replication that
      retains its pro-oncogenic properties. During the course of HCV infection, occult
      HBV infection may worsen liver damage induced by HCV and reduce the response to
      HCV antiviral treatment. Occult HBV infection is a frequent phenomenon and HBV
      DNA testing with highly sensitive PCR in the clinical setting is therefore
      becoming of paramount importance.

PMID- 16461219
TI  - The use of the OraSure collection device for hepatitis virus testing in health
      care settings.
AB  - Oral mucosal transudate (OMT) has levels of IgG and IgA that, although lower than
      in serum, are of the same specificity as serum. Blood can be a difficult sample
      to take especially from persons with an aversion to the process or with poor
      veins. There is also a small exposure risk to the phlebotomist. OMT has been
      shown to be useful in screening for a range of bloodborne viruses, however, the
      ELISA assays need to be modified, usually by increasing test volumes and
      incubation times and/or by modifying the substrate. A number of commercial serum
      kits have been modified successfully in this way. The major roles for these
      assays are for epidemiology or for screening high risk populations. If used for
      screening, it is imperative that any positive is confirmed by a serum test. The
      use of OMT samples using the OraSure(R) collection device, which is FDA approved
      and with which we have the most experience, has increased in recent years in
      community health care settings, with positive feedback from users.

PMID- 16461220
TI  - Software and expert system for the management of chronic hepatitis B.
AB  - Whereas the doubling time of overall biomedical knowledge bases has been
      estimated at about 19 years, the body of indexed information related to HBV has
      doubled in the last 8 years; the one related to HBV and antivirals has doubled in
      the last 5 years and the one related to Interferon and contraindications has
      doubled in less than 48 months. In Hepatology, as well as in other fast changing
      areas of medicine, the demand that clinical decision should always be based on
      the best verified knowledge available, is becoming more and more difficult to
      comply with. The Italian network of competence for hepatic diseases (Liver Unit
      Networks Association or LUNA) was established in 2003 with the patronage of the
      Italian Ministry of Health, with the primary goal of promoting advanced clinical
      research and real-time information exchange among the participating centres,
      facilitating knowledge sharing and identification of best practices. The ICT
      infrastructure designed for this purpose includes four sets of online accessible
      software tools:

PMID- 16461221
TI  - Resistance of human hepatitis B virus to reverse transcriptase inhibitors: from
      genotypic to phenotypic testing.
AB  - The treatment of HBV infected patients with analogues of nucleos(t)ides,
      including lamivudine and adefovir dipivoxil, has significantly increased the rate
      of anti-HBe seroconversion and therefore reduced the impact of chronic hepatitis
      B (CHB) on liver disease. Altogether, these antivirals have offered novel options
      for the treatment of patients who did not respond to previous therapy with
      interferon alpha, the only available treatment against CHB until 1998. However,
      therapies using analogues of nucleos(t)ides have been confronted with viral
      resistances which are often associated to with worsening of liver disease. Drug
      resistance is conferred by the appearance of one or several mutations within the
      HBV polymerase gene. These mutations confer to the mutant viral population a
      phenotypic advantage over the wild-type pretherapeutic viral quasispecies, as
      they induce a reduction of drug susceptibility of mutant strains in vivo. This
      reduction of drug susceptibility can be as well measured in vitro, i.e in cell
      culture, using phenotypic assays. The detection of these mutations has become of
      crucial importance to better adapt clinical option to the virological status of
      the patient. Genotypic and more recently phenotypic assays have been developed
      and both assays can be used for drug resistance testing. Genotypic assay gives
      information about already characterized mutations associated with viral
      resistance, while phenotypic testing measures the overall drug susceptibility of
      patient-derived viral strains in cell culture. These assays are described and
      their potential use in the clinical setting is discussed.

PMID- 16461222
TI  - Detection of hepatitis B virus genotypes and mutants: current status.
AB  - Characterization results of the hepatitis B virus (HBV) genome before, during and
      after antiviral treatment have changed in the last year for a number of reasons.
      First of all, with the introduction of more nucleoside and nucleotide antiviral
      therapies, it has become clear that variants or mutants do emerge in time. Viral
      genomic changes in the HBV polymerase gene can result in a direct antiviral
      effect, but compensatory mutations can also be identified during prolonged
      treatment periods. Furthermore, there is an increasing number of reports
      suggesting that HBV genotypes can be related to, for example, disease progression
      or the effect of antiviral treatment itself (alpha-interferon or lamivudine).
      Combined with HBV DNA viral load monitoring, an increase in viral load or a
      limited reduction during treatment is indicative of genomic changes related to
      resistance. However, these genomic changes can also be present in the absence of
      an increase in HBV DNA. Methodologies for the detection of these variants, as
      well as the determination of genotypes, are rather straightforward. Sequence
      analysis is time-consuming and expensive, but provides the most information,
      particularly if not all information on mutations related to antiviral resistance
      is known. However, the sensitivity of direct sequencing for the presence of minor
      variant populations is poor, and no mixtures of variant populations are, in
      general, detected. The ability to detect minor populations and, if possible, even
      quantify them, gives more insightful information on the dynamic evolution of the
      virus itself. Antiviral treatment can result in the appearance of more than one
      population of variants, which can be present for a prolonged period of time, and
      even remain undetected with current technologies. However, screening specifically
      for these variant populations before starting treatment for so-called untreated
      patients (who have received no antiviral treatment for, e.g., 6 months) has
      already shown that the effects of treatment can be biased. Furthermore, the
      detection of more dynamic viral populations - including both wild-type and
      resistant variants - during, but also after therapy, does provide helpful
      information in the analysis of virological data. Technologies enabling the
      detection and quantification of these variant populations are presented and
      discussed.

PMID- 16461223
TI  - Immune system and hepatitis B virus infection.
AB  - The immune system plays an important role in determining the outcome of hepatitis
      B virus (HBV) infection. This is because recovery from of acute HBV infection is
      associated with a clear division in the profile of adaptive immune response.
      Multispecific antiviral CD4 and CD8 responses with a type 1 cytokine production
      can be observed in patients who recover from acute HBV infection. On the other
      hand, those who develop chronic infection tend to have a weak virus specific T
      cell response. Therapeutic strategies aimed at correcting this defective T cell
      reactivity could represent a complementary approach to the cure of chronic HBV
      infection.

PMID- 16461224
TI  - The DNA-Chip technology as a new molecular tool for the detection of HBV mutants.
AB  - Genetic variability of the Hepatitis B virus (HBV) strongly impacts the natural
      history of infection and the efficiency of diagnosis, vaccination and treatment.
      A genotypc assay able to provide genetic information on all HBV genes would be a
      very important tool for clinicians and epidemiologists. The DNA-Chip technology
      has proved to be powerful and convenient for the diagnosis of infectious diseases
      due to bacteria and viruses. We have designed a genotyping assay based on
      polymerase chain reaction and DNA-Chip for HBV Starting from a unique specimen,
      analysis of polymorphisms at 150 positions along the genome and 383 mutations is
      possible as well as the determination of the genotype. Preliminary experiments
      with plasmas from infected patients show that results obtained with this reagent
      are strongly correlated with those obtained with sequencing.

PMID- 16461225
TI  - Animal models for the study of HBV replication and its variants.
AB  - Enormous progresses in hepatitis B virus research have been made through the
      identification of avian and mammalian HBV related viruses, which offer ample
      opportunities for studies in naturally occurring hosts. However, none of these
      natural hosts belongs to the commonly used laboratory animals, and the
      development of various mouse strains carrying HBV transgenes offered unique
      opportunities to investigate some mechanisms of viral pathogenesis. Furthermore,
      the need to perform infection studies in a system harbouring HBV-permissive
      hepatocytes has lately led researchers to create new challenging human mouse
      chimera models of HBV infection. In this review, we will overview the type of
      animal models currently available in hepadnavirus research.

PMID- 16461226
TI  - Molecular epidemiology of chronic hepatitis B virus infection in northern Poland.
AB  - Hepatitis B virus (HBV) infection is a global health problem, with more than 350
      million people chronically infected worldwide. The chronic HBV infection in
      Poland is also an essential medical and social problem. Starting from 1993, a
      steady decline of the incidence of HBV has been observed, reaching the estimated
      rate of 4.5 per 100 000 in 2004. Nothing is known about the genetic variability
      of HBV in Poland, the occurrence and spreading of genetic variants and mutants of
      hepatitis B virus in the population of Polish patients during the course of the
      disease and in relation to antiviral treatment. It is very interesting to study
      the molecular epidemiology of the Polish population regarding hepatitis B virus
      infection as Poland is still ethnically a uniform country, with no more than 3-4%
      of ethnic minorities. The first results regarding distribution of HBV genotypes
      and serotypes in northern Poland have been published by our group in 2003 and
      2004. This work was part of a scientific project supported by the Fifth Framework
      Programme initiative of the European Union, entitled "Emerging variants of
      hepatitis B virus: new tools for epidemiological survey, diagnosis of infection,
      and monitoring of drug resistance". In the course of the project more than 200
      hepatitis B infected patients from the northern part of Poland have been
      enrolled, diagnosed and - if the viral load of HBV was suitable for analysis -
      genotyped by sequencing of the HBV pol/S gene fragment. This review presents the
      main characteristics and some interesting aspects of the studied cohort of
      chronically infected patients from northern Poland as well as the molecular
      epidemiology.

PMID- 16461227
TI  - DNA-designed avian IgY antibodies: novel tools for research, diagnostics and
      therapy.
AB  - We have recently demonstrated, using the duck Hepatitis B virus (DHBV) model,
      closely related to human HBV, that following DNA immunization of breeding ducks
      with a plasmid encoding the targeted protein, specific and biologically active
      IgY (egg yolk immunoglobulines) are vertically transmitted from their serum into
      the egg yolk from which they can be extracted and purified. Thus an egg can be
      considered as a small "factory" for antibody production, since about 60-100 mg of
      purified IgY can be obtained from each egg yolk of a DNA-immunized duck. One of
      the major advantages of this new method of "DNA-designed" IgY antibodies is their
      production via immunization with a gene vector that expresses a corresponding
      antibody in situ in the cells of an avian host. Therefore this approach allows
      direct generation of antibodies from plasmid DNA and avoids the costly and
      tedious preparation of purified antigens required for conventional antibody
      production. In addition, duck IgY are of remarkable high affinity, avidity and
      are highly neutralizing. Moreover, the epitope pattern of IgY generated by DNA
      immunization of ducks is closely related to that observed in viral infection.
      Such duck IgY are also of particular value as immunodiagnostic tools, since they
      do not cross-react serologically with mammalian immunoglobulins and complement.
      Because IgY are resistant to the gastric barrier, the recently described DNA
      designed IgY specific to H. pylori Urease B can be of particular interest for
      passive immunotherapy of gastrointestinal tract infections. Another interesting
      application is the recent generation in our laboratory of DNA-designed IgY
      antibodies specific to HBsAg mutants. These antibodies are currently being used
      to design new diagnostic assay for detection of HBV mutants that are undetectable
      by actual tests. Moreover, this approach allowing a quick and inexpensive
      production of a new generation of antibodies will provide pertinent tools to link
      the fields of genomics and protcomics.

PMID- 16461228
TI  - HBV induced carcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is one of the rare human neoplasms associated with
      viral infections. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the
      most important etiological factors of HCC, accounting for more than 70% of cases
      worldwide. The risk of HCC development is greatly increased in chronic viral
      carriers exposed to other recognized risk factors, including exposure to
      aflatoxin B1, alcoholic cirrhosis and diabetes. The importance of HBV genotypes
      and precore or core promoter mutants remains incompletely understood. The role of
      HBV in tumour formation appears to be complex and may involve both direct and
      indirect mechanisms. Integration of HBV DNA into the host genome occurs at early
      steps of clonal tumour expansion, and it has been shown to induce direct
      insertional mutagenesis of diverse cancer-related genes in a number of cases.
      Chronic liver inflammation and hepatic regeneration induced by cellular immune
      responses may favour the accumulation of genetic alterations in infected
      hepatocytes. Prolonged expression of the viral regulatory protein HBx and the
      large envelope protein LHBs may contribute in deregulating the cellular
      transcription program and proliferation control, and sensitize liver cells to
      carcinogenic factors. Recent genetic studies have provided insight into the
      mechanisms underlying viral-associated hepatocarcinogenesis. It has been shown
      that the rate of chromosomal alterations is significantly increased in HBV
      related tumours compared with tumours associated with other risk factors. HBV
      might therefore play a role in enhancing genomic instability. Inactivation of p53
      by mutations and regional allelic deletions is found more frequently in tumours
      associated with HBV infection. By contrast, HBV related tumours harbour a low
      rate of beta-catenin mutations. Together, these data strongly support the notion
      that chronic HBV infection might trigger specific oncogenic pathways, thus
      playing a role beyond stimulation of host immune responses and chronic necro
      inflammatory liver disease.

PMID- 16461229
TI  - Hepatitis B virus genome variability and disease progression: the impact of pre
      core mutants and HBV genotypes.
AB  - The hepatitis B virus (HBV), a member of the Hepadnaviridae family, is prone to
      mutations due to its asymmetric replication via reverse transcription of an RNA
      intermediate. The estimated mutation rate of the hepadnavirus genome is 2 x 10(4)
      base substitutions/site/year. This mutation rate is approximately 100 times
      higher than that of other DNA viruses but between 100 and 1000 times lower than
      that of RNA viruses. Analyses of both naturally occurring viral variants and in
      vitro mutagenesis studies have identified some mutations that have a role in
      viral latency, pathogenesis of liver disease, immune escape, and resistance to
      antiviral therapy.

PMID- 16461230
TI  - Identification of hepatitis B virus genome in faecal sample from wild living
      chimpanzee (Pan troglodytes troglodytes) in Gabon.
AB  - Non-invasive faecal sampling in the equatorial forest in Gabon allowed the first
      identification of the hepatitis B virus (HBV-Ch(RC170)) genome in samples
      collected from wild chimpanzees (Pan troglodytes troglodytes). The HBV
      Ch(RCl70)sequence clustered with 100% bootstrap support with previous viral
      sequences obtained from Pan troglodytes subspecies. This is the first evidence of
      HBV infection in wild apes and confirms that the HBV-like strains thus far
      characterized in captive apes are directly related to those circulating in the
      wild.

PMID- 16461231
TI  - Phenotyping hepatitis B virus variants: from transfection towards a small animal
      in vivo infection model.
AB  - The existence of vaccine escape and drug resistant hepatitis B virus (HBV)
      variants is now well established, and various of the underlying prototypic
      mutations have been defined. Genotypic detection of such variants allows to
      predict their clinical phenotype. However, the relevance of non-predefined
      mutations occurring during therapy can be assessed only by phenotypic assays. The
      fundamental properties of a functional virus are the ability to replicate the
      genome, to form infectious virions, and to cope with the host defense in order to
      establish and maintain infection; a virus meeting all these criteria is
      biologically fit. At present, HBV DNA transfection provides a reliable method to
      address replication-competence and physical formation of complete virus
      particles. The inherent inter-experiment variability of transient transfection
      can be overcome by stable cell lines expressing wild-type and prototypic variant
      HBVs. Such cell lines provide important tools for studying basic aspects of HBV
      replication as well as for drug discovery. Phenotypic assays measuring HBV
      infectivity are less advanced but several surrogate systems obviating the need
      for primary human hepatocyte cultures are being established. The ultimate, and
      most desirable, phenotypic assay system would be a small, immuno-competent
      experimental animal in which human HBV can establish chronic infection. Only this
      would allow to fully address the fitness of HBV variants, and thus to assess the
      risk of their spreading in the general population. Various ways towards this goal
      can be envisaged but recent model studies in the duck HBV system indicate that
      much more has to be learned on the molecular determinants of hepadnaviral host
      range to rationally design such experiments.

PMID- 16461232
TI  - Therapeutic vaccination for chronic infectious diseases: lessons from HIV-1.
AB  - Most therapeutic vaccines are usually divided into two groups according to their
      mode of action on immunity, based on the induction of either a Immoral response
      (antibodies) or a cellular response, mostly cytotoxic T lymphocytes (CTLs). The
      latter ones are in fact the most promising candidates for the treatment of cancer
      and chronic viral infections. However, we must admit that the design of such
      vaccines is far from being simple as the biology of the chronic infectious
      diseases involves complex issues such as viral latency, the existence of
      reservoirs or immune escape mechanisms. Furthermore, the concept of therapeutic
      vaccination implies that the host immune system is still competent for eliciting
      an immune response after vaccination, but patients suffering from chronic
      infectious diseases usually exhibit impaired immune defenses. To overcome this
      challenge, the actual tendency is to combine chemotherapy and therapeutic
      vaccination, playing around with schedules of vaccine administration and standard
      chemotherapy. To illustrate the different steps in the design and testing of a
      therapeutic vaccine, the human immunodeficiency virus (HIV-1) for which the
      efficacy of therapeutic vaccines is currently being evaluated, could serve as a
      model. Specific points like the rationale of using HIV-1 regulatory genes instead
      of structural genes, the possibility of using multiple injections of vaccine
      candidates or the importance of pre-existing immunity will be emphasized,
      together with the risks of inducing the emergence of new HIV-1 variants upon
      vaccine treatment of chronically infected HIV-1 patients. The current expertise
      in the field of therapeutic vaccines in chronically infected HIV-1 patients could
      be of interest for the design of a therapeutic vaccine for HBV infection.

PMID- 16461233
TI  - The competing roles of virus replication and hepatocyte death rates in the
      emergence of drug-resistant mutants: theoretical considerations.
AB  - Lamivudine therapy of individuals chronically infected with hepatitis B virus
      (HBV) may eventually fail due to the emergence of drug-resistant mutants.
      Nonetheless, the durability of the response generally exceeds 6-12 months. This
      durability appeared surprising in view of published evidence that the replication
      rate of drug-resistant mutants might be at least 10% of the replication rate of
      uninhibited wild-type virus. In this case, it might be expected that pre-existing
      mutants would rapidly spread to any uninfected hepatocytes that arose during
      therapy. To gain insights into why therapy is at least transiently successful in
      many patients, we constructed a computational model of the infected liver to
      account for the rates of replication of wild-type and drug-resistant mutant
      viruses, rates of death of infected and uninfected hepatocytes, rates of
      spontaneous mutation to drug resistance, opportunity for polymerase trans
      complementation, and the survival or loss of covalently closed circular DNA
      (cccDNA) during cell division. The analyses suggest that either drug-resistant
      mutants have much lower replication rates than suspected, or that spread of virus
      to uninfected hepatocytes that arise in the chronically infected liver is much
      slower than during de novo infections.

PMID- 16461234
TI  - Genetic diversity and evolution of hepatitis C virus in the Latin American
      region.
AB  - Hepatitis C virus (HCV) has been the subject of intense research and clinical
      investigations, as a consequence of the recognition of its major role in human
      disease. HCV evolution is a highly dynamic process. HCV exploits all known
      mechanisms of genetic variation, such as recombination and mutation, to ensure
      its survival. Like most RNA viruses, HCV circulates in vivo as a complex
      population of different but closely related variants, commonly referred to as a
      quasi species. This work describes the genetic variability of HCV in Latin
      America, with special emphasis on its diversification and recombination in this
      area of the world, and discusses how our knowledge of these issues can contribute
      to its control.

PMID- 16461235
TI  - Progress in vaccination against hepatitis B in the Americas.
AB  - Hepatitis B is a serious public health problem leading to chronic infection,
      liver cirrhosis, and hepatocellular carcinoma. The World Health Organization
      (WHO) and the Pan American Health Organization (PAHO) recommend routine universal
      infant vaccination against hepatitis B as the main strategy for the control
      hepatitis B and its severe consequences. PAHO additionally recommends routinely
      vaccinating healthcare workers. As of 2005, all countries in the Americas, except
      Haiti and Dominica, have hepatitis B vaccine in their childhood immunization
      schedule; 13 countries/territories include a hepatitis B dose given at birth.
      Hepatitis B vaccine has been incorporated into national schedules using different
      modalities; notably, 28 countries use it as a combination vaccine diphtheria
      tetanus pertussis + Haemophilus influenzae type b + hepatitis B (DTP+Hib+Hep B)
      for infants. Coverage levels for the third dose of hepatitis B are usually over
      80%; however, hepatitis B vaccine coverage overall is lower than for the third
      dose of DTP. Insufficient information is available at this time to assess the use
      of hepatitis B vaccine in healthcare workers in the Americas. The most important
      factor associated with the success in the implementation of hepatitis B
      vaccination has been the strong commitment of country governments. This
      experience can be used as a model when implementing new technologies in health as
      they become available. However, much still needs to be done to improve hepatitis
      B coverage.

PMID- 16461236
TI  - Antibodies to hepatitis C and other viral markersin multi-transfused patients
      from Argentina.
AB  - BACKGROUND: The knowledge of transfusion-transmitted viral infections in
      Argentina is scarce. A regional study organized by the Pan American Health
      Organization let us asses the current status. OBJECTIVES: To estimate the
      prevalence of HCV, HBV and HIV infection in a population of multi-transfused
      Argentinean patients. STUDY DESIGN: Multi-center, cross sectional study of 504
      patients from national referral institutions in Buenos Aires, who had received
      more than ten units of blood products in more than two occasions. Demographic and
      clinical data were collected using a standardized questionnaire. Blood samples
      were analyzed for a-HCV, a-HIV, HBsAg and a-HBcore. RESULTS: Patients belonged to
      five diagnostic categories: onco-hematology (309; 61.3%); hemophilia (96; 19%);
      acute blood loss (54; 10.7% ); hemoglobinopathies (35; 6.9%); and hemodialysis
      (5; 1% ); five patients (1%) had two of the previous conditions. Overall
      prevalence rates of viral markers were: a-HCV 9.3% (CI(95%): 6.7-12.0); a-HBcore
      4.8% (CI(95): 2.8-6.7); a-HIV 1.2% (CI(95%): 0.14-2.2) and HBsAg 0.20%(CI(95%):
      0.2-0.59). The highest prevalence rates were found among patients living with
      hemophilia (PLH). There was a significant statistical association (p < 10(-5), OR
      =78.8 [29.7-209.7]) between a-HCV infection and having been transfused before
      1993, when screening blood donors for a-HCV became mandatory in our country. The
      subpopulation of patients exposed to transfusion before 1993 was conformed mostly
      by PLH (70.9%) and hemoglobinopathies (18.6%). In this subpopulation, we found a
      significant association (p < 10(Dot;), OR -40 [5.68-281.66]) between years of
      exposure to transfusion and a-HCV among the patients under the median age (21.95
      years old); however, there was no association for those above the median age
      (p=0.111). CONCLUSION: a-HCV was found to be the most prevalent infection in the
      multi-transfused patient population under study. Most infected individuals were
      PLH, transfused before 1993. This study will provide support for further research
      aimed at improving blood safety in Argentina.

PMID- 16461237
TI  - Transfusion-transmitted infections among multi-transfused patients in Brazil.
AB  - BACKGROUND: Transfusion-transmitted infections (TTI) continue to be a problem in
      many parts of the world, and multi-transfused patients (MTP) are at a
      particularly increased risk of TTI. OBJECTIVES: to estimate the prevalence of TTI
      among multi-transfused patients in Brazil, and to understand the epidemiological
      characteristics of TTI among these patients. STUDY DESIGN: cross-sectional study
      of 353 MTP, who were interviewed using a structured questionnaire and tested for
      serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human
      immunodeficiency virus (HIV) infection. RESULTS: the overall prevalence of HCV,
      HIV, HBV and co-infection among MTP were 16.7%, 1.7%, 0.8% and 1.7% respectively.
      A dose-effect relationship could be detected between the number of units
      transfused and HCV infection. Other non-transfusion related (NTR) risk factors
      for HCV did not confer any excess risk of HCV infection to MTP. CONCLUSIONS: HCV
      infection was the most prevalent TTI among MTP, and remains a major health
      problem for these patients. A dose-effect relationship could be detected between
      HCV and the number of units transfused. The implementation of measures such as
      donor education programs, standards for donor selection criteria, and of improved
      serological screening protocols, paralleled the decline in the prevalence of TTI,
      specially of HCV, observed in MTP, underscoring the importance of such measures
      for the reduction of the residual risk of TTI.

PMID- 16461238
TI  - Hepatitis C virus seroprevalence in multi-transfused patients in Colombia.
AB  - BACKGROUND: Hepatitis C Virus (HCV) infection is a public health problem
      worldwide, with particular relevance in multi-transfused patients given that HCV
      is principally transmitted by exposure to infected blood. STUDY DESIGN: Between
      February and September 2003 a cross-sectional study was carried out in four
      hospital centres in Bogota and Medellin, Colombia, to determine the risk factors
      for HCV infection in 500 multi-transfused patients. RESULTS: The study population
      was distributed in five groups: haemophilia, haemodyalsis, acute bleeding,
      ontological illnesses and sickle cell disease or thalassemia. Serum samples from
      patients were tested for HCV antibodies (Asxym, Abbott). An overall prevalence
      (9.0%; 95% confidence interval (CI): 6.4-11.6) (45/500) of HCV infection was
      found. Anti-HCV antibodies were detected in 32.2% of patients with haemophilia,
      6.1% of patients undergoing haemodialysis, 7.1% of patients with sickle cell
      disease or thalassemia, 2.6% of patients with acute bleeding and 3.4% of patients
      with ontological or hematological diseases. The main risk factors associated with
      infection by HCV were: to be hemophilic (odds ratio, OR = 18.03; 95% Cl: 3.96
      114.17), having received transfusions before 1995 (OR = 12.27; 95% Cl: 5.57
      27.69), and having received more than 48 units of blood components (OR = 6.08;
      95% CI: 3.06-12.1). In the multivariate analysis, only the year of transfusions
      (before 1995) remained significantly associated with risk of infection by HCV.
      CONCLUSIONS: The data show a 3-fold reduction in the infection risk between 1993
      and 1995, when the serological screening for HCV in blood donors was being
      introduced. A reduction greater than 90% was achieved by 1995 when the screening
      coverage reached 99%.

PMID- 16461239
TI  - Hepatitis C virus antibodies and other markers of blood-transfusion-transmitted
      infection in multi-transfused Cuban patients.
AB  - BACKGROUND: HCV was initially identified in 1989 when it was found to be the
      primary causative agent of non-A, non-B hepatitis,a condition associated with
      high rates of progressive and end-stage liver disease, cirrhosis, and
      hepatocellular carcinoma. Since then, appreciation of the significant worldwide
      health impact of HCV infection has grown. HCV infection was identified as a
      public health problem in Cuba in the 1990s. Despite universal blood donor
      screening, which was achieved in 1995 using the Cuban immunoassay system UMELISA
      HCV, the infection is still found in multi-transfused patients. OBJECTIVES: To
      determine the magnitude of HCV, HBV and HIV-1&2 infections among Cuban blood
      recipients and to assess the role of potential risk factors. STUDY DESIGN: Cross
      sectional study of 318 patients from Havana City, Pinar del Rio and Villa Clara,
      who had been previously treated with 10 or more units of allogenic blood or blood
      components in at least two different occasions. The patients were evaluated for
      HCV Ab, HBsAg, anti-HBc Ab, and HIV-1&2 Ab. Data management and statistical
      analysis were performed using EpiInfo and SSPS software. RESULTS: Prevalence
      rates were 51.6% for HCV Ab; 5.3% for HBsAg; 45.0% for anti-HBc and 0% for HIV
      1&2 Ab. Ten (3.1%) patients were co-infected with HCV and HBV Blood transfusion
      was not identified as the main risk factor for HCV transmission. The number of
      blood units received by the patients was not statistically associated with the
      HCV Ab prevalence. CONCLUSIONS: Infection with HCV was identified more frequently
      than HBV and HIV among our study population. Patients undergoing hemodialysis
      were at the highest risk of becoming infected. Medical procedures including
      surgery, transplantation, invasive odontology, and sharing or reuse of needles
      and syringes, are associated with higher HCV Ab seroprevalences compared with
      blood transfusion alone.

PMID- 16461241
TI  - Transfusion-transmitted infections inmulti-transfused patients in Honduras.
AB  - BACKGROUND: Monitoring infectivity markers in multi-transfused patients is an
      important indicator of the efficiency and quality of testing in blood centers.
      This study is part of a regional initiative to bring both national and regional
      attention to the problem of hepatitis C, compare the threat of HCV to that of HBV
      and HIV; assess the risks for viral infection of using different blood products
      and implementing different transfusion practices, and contribute to a better
      understanding of the state of blood safety in the region. STUDY DESIGN AND
      METHODS: A cross sectional study was conducted from September 2002 to August 2003
      and included multi-transfused patients from eight private, public and Social
      Security hospitals from Tegucigalpa and San Pedro Sula, Honduras. A survey was
      completed for each patient which included demographic and clinical data. Patients
      were tested for HBsAg, anti-HBc, anti-HIV and anti-HCV Effects of the exposure to
      blood products, to whole blood; to lyophilized factor VIII in patients living
      with hemophilia on the prevalence of HBV, HCV and HIV infection were evaluated.
      RESULTS: Five hundred and two patients were enrolled in the study; 11% were
      positive for HBsAg; 27% for anti-HBc; 7% for HCV and 1% for HIV One point six
      percent of hemophilia patients were positive for HBsAg; 38% were positive for
      anti-HBc and 26.9% for HCV A dose effect between the exposure to blood products
      and prevalence of HCV was found (p < 0.05). It was not possible to show a dose
      effect between the exposure to blood products and prevalence of either HBV or HIV
      in any of the subpopulations studied. CONCLUSIONS: The transfusion of blood
      products seems to be the main factor for HCV seropositivity in the subpopulation
      of patients studied. Additional work is needed to elucidate the risk factors
      associated with HBV infection in Honduras.

PMID- 16461240
TI  - Improving the safety of the blood supply in Ecuador through external performance
      evaluation of serological screening of blood donors.
AB  - BACKGROUND: The Ecuadorian National Blood System collects approximately 100 000
      units of blood per year. Screening for infectious agents is conducted by 23
      autonomous blood services using different methodologies and reagents. OBJECTIVES:
      To evaluate the performance of serology testing by laboratories of the Ecuadorian
      National Blood Bank System. STUDY DESIGN: Four proficiency panels were
      distributed between April 2003 and December 2004 containing samples that were
      characterized as either reactive or non-reactive for hepatitis B surface antigen
      (HBsAg), antibodies against hepatitis C virus (HCV), and antibodies against human
      immunodeficiency virus (HIV). Laboratories were classified according to the
      volume of blood units processed per year, as small (<5000), medium (5000-12000)
      and large (>12000). RESULTS: Large and medium blood services consistently
      obtained better results than small ones. All of the 37 anti-HIV antibody false
      negative results and all of the 20 HBsAg false negative results were reported by
      small laboratories. False negative results were associated with the use of rapid
      tests. Laboratories using rapid tests and certain lots of an enzyme-linked
      immunosorbent assay (ELISA) failed to detect HCV reactive sera in December 2004.
      CONCLUSION: The high number of incorrect results in most small blood services
      indicates serious weaknesses in blood screening that require urgent corrective
      action. The National Blood System has implemented on-site audits, training,
      technical assistance, and increased oversight. The long-term proposal is to
      centralize blood testing in two large blood centers. The results presented here
      underline the importance of strengthening the regulatory framework and oversight
      in Ecuador and highlight the role of external performance evaluation programs for
      blood safety improvement.

PMID- 16461242
TI  - Epidemiology of transfusion-transmitted infections among multi-transfused
      patients in seven hospitals in Peru.
AB  - BACKGROUND: Transfusion-transmitted infections (TTIs) constitute a major health
      problem worldwide where routine screening of blood or blood products is
      improperly done, and where non-medical injecting medications and/or drug use are
      prevalent. Prevalence and risk factors vary by geographic location and by the
      specific TTI (including HIV-1, HBV, HCV and HTLV-I). OBJECTIVE: To determine the
      prevalence and risk factors associated with TTIs among a sample of multi
      transfused adult patients in Peru. STUDY DESIGN: A cross-sectional multi-center
      study was conducted across seven major hospitals in Peru from February 2003 to
      September 2004. Self-reported behavior information (medical procedures, number of
      sexual partners, and drug use history) was analyzed, along with a review of
      exposure history from hospital medical records. Prevalences were calculated by
      TTI for different exposures, along with unadjusted and adjusted odds ratios for
      infection risk. RESULTS: Overall, 192 (54.7%) of 351 multi-transfused patients
      were found infected with one or more TTIs. Number of transfusion units, years of
      transfusion history (6 or more), and number of treatment facilities (2 or more)
      were associated with HCV infection. Hemodialysis history was a common risk factor
      associated with HBV, HCV and HTLV-I infection. HIV infection was associated only
      with total number of transfusion units received. CONCLUSIONS: High prevalences of
      HBV and HCV infection were found among Peruvian multi-transfused patients and
      were associated with a past history and number of blood transfusions, as well as
      with past hemodialysis procedures. TTIs continue to represent a significant
      public health problem in Peru. Continued vigilant attention to blood safety
      procedures, including universal screening and health care provider education, is
      recommended.

PMID- 16461243
TI  - Risk factors for hepatitis B and C in multi-transfused patients in Uruguay.
AB  - BACKGROUND: In spite of the progress made in the prevention of transfusion
      transmitted infections over the last years, these still occur. It was considered
      that infection by hepatitis B (HBV) and C (HCV) viruses could be a major problem
      in Uruguay, especially among high-risk individuals, such as multi-transfused
      patients. OBJECTIVES: To assess the prevalence of HBV and HCV infection among
      multi-transfused Uruguayan patients and the impact of serological screening; to
      evaluate the role of number of transfusions and other potential risk factors for
      the acquisition of HBV and HCV infection. STUDY DESIGN: Cross-sectional study of
      HCV antibodies, HBV surface antigen (HBsAg) and HBV core antibodies (HBcAc) in
      409 multi-transfused patients. RESULTS: Of 409 patients studied, 147 (35.9%)
      received blood products due to acute bleeding, 118 (28.9%) were hemato
      oncological, 75 (18.3%) hemophiliacs, 64 (15.6%) were on hemodialysis and 5
      (1.2%) suffered sickle cell anemia. Prevalence of HCV antibody was 12.7%. Of the
      HCV positive patients, 45 were hemophiliacs, for a prevalence rate of 60.0%. The
      prevalence rates for hemodialysis and acute bleeding patients were 6.3% and 2.0%,
      respectively. Prevalence of HBsAg was 1.0%; 16.6% of subjects were positive for
      HBcAc. The prevalence rates of HBcAc were 48.0%, 15.0% and 3.1% among
      hemophiliacs, acute bleeding and hemodialysis patients, respectively. There was a
      direct relationship between the number of products transfused and prevalence of
      both hepatitis C antibodies and HBcAc. Higher prevalence of HCV and HBcAc was
      observed among the group of patients who received transfusions before the
      systematic screening of blood donors. CONCLUSIONS: Exposure to blood transfusions
      was the main risk factor for HCV and HBV infection. The systematic serological
      screening of blood donors was highly effective in reducing transfusion
      transmitted infections.

PMID- 16461244
TI  - Safety of blood supply in the Caribbean countries: role of screening blood donors
      for markers of hepatitis B and C viruses.
AB  - BACKGROUND: Blood transfusions carry risks of untoward reactions, including the
      transmission of infections, such as hepatitis B and C. Proper blood donor
      recruitment and selection, and adequate laboratory screening for infectious
      markers diminish the risk of transfusion-transmitted infections. OBJECTIVES: To
      estimate the potential risk of acquiring transfusion-transmitted infections by
      hepatitis B or hepatitis C in 24 Caribbean countries during the period of 1996 to
      2003. STUDY DESIGN: Official national reports for 1996, 2000-2003 of the yearly
      number of blood donors, screening coverage, and prevalence of serological markers
      for infectious diseases were used to estimate the risk of patients receiving an
      HBV- or HCV-positive unit of blood, and of developing an infection after
      receiving a positive unit. Estimates of number of infections transmitted through
      transfusion and number of infections prevented by screening of blood were also
      obtained. RESULTS: During the period analyzed, HBV screening coverage among blood
      donors was 100% in all countries with the exception of Grenada (0% in 1996) and
      Saint Lucia (99.5% in 2002). For HCV, only 10 countries reported universal
      screening in 1996, while 15 did in 2003. The number of countries that did not
      screen any units for HCV decreased from 11 in 1996 to five in 2003. In general,
      high prevalence rates of HBV (10-75 per 1000 donors) and HCV (7-19.3 per 1000
      donors) markers were found in the majority of countries. We estimated that 235
      infections by HCV (1:12471 donations) and two infections by HBV (1:1465373) were
      transmitted through transfusion because of lack of screening. On the other hand,
      screening of blood for transfusion prevented 21 005 HCV and 22 100 HBV
      infections. CONCLUSIONS: Blood donor recruitment and coverage of screening for
      transfusion-transmitted infections, especially HCV, must be improved in the
      Caribbean countries.

PMID- 16461245
TI  - Molecular epidemiology of hepatitis B virus in Latin America.
AB  - Hepatitis B virus (HBV) is an etiological agent of acute and chronic liver
      disease existing throughout the world. The high genetic variability of HBV is
      reflected by eight genotypes (A to H), each one with a particular geographical
      prevalence. The global pattern of HBV genotypes is associated with the
      distribution of human populations among the different continents and may reflect
      the patterns of human migrations. Genotypes F and H are considered indigenous to
      Latin America. The most prevalent genetic group of Central and South America,
      genotype F, is subdivided into two subtypes and five clusters associated with
      defined geographic areas. Genotype H has been described in Mexico and Central
      America. This pattern provides a tool to reconstruct the initial immigration of
      ancestral Amerindians from Asia and their further spread through Central and
      South America. Other HBV genotypes found in different Latin American countries
      may reflect migration from other geographical areas into the region. Genotypes A
      and D are the signature of the European colonization that started in the
      sixteenth century, including slave trade from Africa. Genotypes B and C indicate
      the arrival of people from Southeast Asia. The impact of HBV genotypes on the
      natural course of HBV infection and response to treatment has been studied
      recently and controversial results have been obtained. The majority of the
      current information concerns with genotypes B and C. In contrast, very few data
      are available on the Latin American HBV genotypes F and H. It has been reported
      that liver failure and death may be more frequent in patients infected with
      genotype F. More studies are needed to assess the association between H13V
      genotypes and clinical course of infection, especially in Latin America.

PMID- 16461246
TI  - Parent resuscitation preferences for young people with severe developmental
      disabilities.
AB  - OBJECTIVE: To determine the relationship of providing explanatory information
      regarding resuscitation to DNR status for parents and guardians of young people
      who reside in a pediatric skilled nursing facility. DESIGN: Retrospective, quasi
      experimental study of policy change, with each individual serving as his or her
      own control. Interval comparisons were made between resuscitation choices before
      and after information was provided to families. For those who were originally in
      the full resuscitation group, comparisons were also made between those who
      changed to DNR and those who did not. SETTING: Pediatric skilled nursing facility
      in Massachusetts. PARTICIPANTS: Sixty individuals with severe mental retardation
      and complex medical problems, between the ages of approximately 2 and 32 years.
      MEASUREMENTS: Review of records regarding resuscitation choices and changes, with
      each person serving as his or her own control. Both univariate and multivariate
      analyses were performed on individuals who were in the full resuscitation group
      at the initiation of the study to determine distinguishing characteristics
      between those who remained in that group from those who changed to DNR. RESULTS:
      The families of 11 (18%) of 60 patients had requested DNR orders prior to
      requirement of written preference for resuscitation or DNR in the event of
      cardiopulmonary arrest. After provision of informative material, there was an
      increase to 26 patients (43%) who were designated DNR (P < . 001). There was no
      significant difference in characteristics between the groups that changed to DNR
      and those that remained full resuscitation, although there was a marginal trend
      of children in the group with an acquired etiology for their developmental
      disabilities were more apt to have their resuscitation status changed than those
      with congenital diagnoses (P = .053). CONCLUSION: When families are provided with
      explanatory information regarding resuscitation in a nonacute, pediatric skilled
      nursing home setting, there is a significant increase in request for DNR.

PMID- 16461247
TI  - Transition to nursing home from assisted living is not associated with dementia
      or dementia-related problem behaviors.
AB  - OBJECTIVES: To examine risk factors for transition from assisted living (AL) care
      to skilled nursing facility (SNF) care in a random sample of adults residing in
      AL. DESIGN: Baseline clinical evaluation and telephone follow-up at 6-month
      intervals for up to 36 months. SETTING: AL facilities in central Maryland.
      PARTICIPANTS: There were 198 participants randomly sampled from AL facilities
      stratified by facility size. MEASUREMENTS: Consensus diagnoses by
      multidisciplinary geriatric psychiatry team as well as a broad range of
      neuropsychiatric and functional scales including Neuropsychiatric Inventory,
      Cornell Scale for Depression in Dementia, Mini-Mental State Exam, and Alzheimer's
      Disease Related Quality of Life Scale, as well as cognitive tests. Possible risk
      factors for transition to SNF were assessed in Cox proportional-hazards
      multivariate regression methods, using a P value less than .05 for statistical
      significance. RESULTS: Twenty-nine participants transitioned to SNF care. Mean AL
      survival time from baseline evaluation was 0.8 (SD 0.6) years for residents
      transitioned to SNF and 1.4 (SD 0.7) years for residents remaining in AL at
      follow-up. Risk factors for transition to SNF included declining health, chronic
      pain, appetite changes, and being widowed, while insomnia was protective against
      transition to SNF. Surprisingly, dementia and neuropsychiatric symptoms did not
      increase risk of transition to SNF. CONCLUSION: Survival time in AL is determined
      by factors similar to those operating on community-dwelling elderly, but dementia
      and neuropsychiatric symptoms do not alter survival time.

PMID- 16461248
TI  - A randomized clinical study of tea catechin inhalation effects on methicillin
      resistant Staphylococcus aureus in disabled elderly patients.
AB  - OBJECTIVES: To evaluate the effects of tea catechin inhalation on methicillin
      resistant Staphylococcus aureus (MRSA) in disabled elderly patients. DESIGN:
      Seven days, randomized, prospective study. SETTING: Three hospitals in Japan.
      PARTICIPANTS: Seventy-two patients aged 78 +/- 11 years (mean age +/- standard
      deviation) with cerebrovascular diseases, classified as disabled according to the
      activity of daily living and were either bedridden or required assistance for
      standing, and showing presence of MRSA in sputum. INTERVENTIONS: Inhalation of 2
      mL tea catechin extract solution along with saline (3.7 mg/mL catechins, 43% of
      catechins are composed of epigallocatechin gallate), or saline alone, 3 times
      daily using a handheld nebulizer for 7 days. MEASUREMENTS: The endpoint of
      efficacy was the reduction rates of MRSA in sputum. The safety measure was the
      adverse events observed during the 7 days of inhalation. RESULTS: The reduction
      rates calculated as the summation of decrease and disappearance of MRSA in sputum
      at 7 days were 47% (17 of 36 patients) in the catechin group and 15% (5 of 33
      patients) in the control group; the difference in the reduction rates between the
      2 groups was statistically significant (P = .014). The disappearance rate of MRSA
      in sputum was higher in the catechin group (31%; 11 patients) when compared with
      the control group (12%; 4 patients), however the difference in the disappearance
      rate between the 2 groups was not statistically significant (P = .091). No
      adverse events, such as respiratory tract obstruction, allergic bronchial spasm,
      or skin eruption, including laboratory changes, were observed during the study.
      CONCLUSION: The catechin inhalation appeared to reduce the MRSA count in sputum.
      However, the application of tea catechin inhalation as a supplementary treatment
      for controlling MRSA infection remains controversial.

PMID- 16461249
TI  - Improved evaluation and management of cognitive impairment: results of a
      comprehensive intervention in long-term care.
AB  - OBJECTIVES: Although as many as 50% of patients in long-term care have dementia,
      it is often not diagnosed and therefore, undertreated. We determined whether an
      intervention could improve the diagnosis and management of patients with
      cognitive impairment (CI) in long-term care. DESIGN, SETTING, AND PARTICIPANTS:
      The assessment phase consisted of a record review of 60 consecutively admitted
      patients to the San Francisco VA Nursing Home Care Unit (NHCU). Cognitive
      impairment was determined by admission MMSE < or = 24, indication of cognitive
      problem on MDS, or chart diagnosis of dementia. The evaluation consisted of a
      repeat chart review of 60 additional consecutively admitted patients.
      INTERVENTION: The intervention consisted of low-cost and easy-to-implement
      educational activities (training, focus groups), strategies to document cognitive
      status, and consultation with dementia experts. MEASUREMENTS/RESULTS: The 2
      cohorts of 60 patients did not differ on demographics or on other characteristics
      (P > .25 for all). Prior to the intervention, of the 23 patients with CI, 52% had
      an identified etiology, 35% had a physician management plan, and 22% had a
      multidisciplinary care plan. Postintervention, of the 22 patients with CI, 91%
      had an identified etiology (P = .007), 86% had a physician plan (P = .001), and
      59% had a multidisciplinary plan (P = .016). CONCLUSIONS: Initial results
      confirmed the underdiagnosis and undertreatment of CI in our long-term care
      facility. Our intervention with educational programs, increased documentation of
      cognitive status, and consultation resulted in increased identification of
      etiology and improved plans for management of patients with CI.

PMID- 16461250
TI  - Alzheimer's treatment in nursing homes: room for improvement.
AB  - Managing Alzheimer's disease (AD) continues to challenge long-term care
      physicians and administrators. Although pharmacologic treatment can substantially
      benefit AD patients in the nursing home setting, common misconceptions and
      skepticism about its value are barriers to treatment use. Aggressive treatment
      for AD maximizes patient function and independence and is cost-effective. Herein
      we discuss state-of-the-art treatment of AD with a view to providing nursing home
      physicians a framework from which to make treatment decisions.

PMID- 16461251
TI  - A comparison of cognitive and functional care differences in four long-term care
      settings.
AB  - Matching residential setting with cognitive and physical abilities is crucial for
      the provision of a supportive long-term care (LTC) environment. This study
      compares the cognitive and functional care differences of LTC residents on
      skilled nursing units designed for dementia care, chronic care, or ambulatory
      care, and an assisted living setting using the Minimum Data Set (MDS) Texas Index
      of Level for Effort (TILE) clinical categories (heavy care,
      rehabilitation/restorative, clinically unstable, clinically stable), MDS
      Activities of Daily Living (ADL), and Mini-Mental State Examination (MMSE). The
      goal of the comparison was to find a parsimonious approach for determining
      resident placement in LTC using the MDS and MMSE. Using a descriptive comparative
      design, the study took place at a not-for-profit, urban, continuing care
      retirement center (CCRC) with a 120-bed skilled nursing facility and a 34-unit
      assisted living facility. Sixty residents, 15 from each of the 3 skilled nursing
      units and assisted living unit, consented to participate. To understand the
      differences in the MDS and MMSE scores between units, a Level of Care Algorithm
      was constructed to analyze resident placement. Results revealed that MDS and MMSE
      scores placed greater than 75% of elders who had extremely poor cognitive or
      physical function but did not discriminate well for residents with moderate
      cognitive and/or physical impairment. For these residents, interaction between
      institutional philosophy (aging in place versus moving to a new location);
      resource availability; and elder, family, and staff values and preferences may
      have influenced placement.

PMID- 16461252
TI  - The application of evidence-based principles of care in older persons (issue 1):
      management of osteoporosis.

PMID- 16461253
TI  - Dementia assessment and management.
AB  - Dementia is a common yet potentially underdiagnosed illness in the long-term care
      setting. Targeted screening for dementia should be routine practice, as a
      diagnosis of dementia will have benefits to the care of the patient. Assessment
      of dementia should proceed in a step-wise approach and should be tailored to the
      needs of the individual patient. Management of dementia involves care for the
      cognitive changes, behavioral changes, functional changes, and emotional issues.
      It also involves the management of other illnesses in light of the dementia,
      consideration of the needs and well-being of the caregiver, and particular
      attention to advanced care planning. Management techniques and goals should
      evolve as the patient's illness progresses. This comprehensive approach to
      management of dementia may reduce morbidity and mortality associated with this
      illness. This model of care provides patients and families with needed
      information and resources, a clear view of prognosis, and necessary attention to
      quality of life issues.

PMID- 16461255
TI  - White Paper on the survey process.

PMID- 16461256
TI  - Time for tea?

PMID- 16461257
TI  - Improving the recognition and management of dementia in long-term care: obstacles
      and opportunities.

PMID- 16461258
TI  - CMS guidelines and improving continence care in nursing homes: the role of the
      medical director.

PMID- 16461259
TI  - The Pay for Performance demonstration program.

PMID- 16461260
TI  - The nursing home physician's point of view on warfarin use.

PMID- 16461261
TI  - Neurobiology tools: flashdancing worms.
AB  - The functional analysis of neuronal circuitry would be facilitated if researchers
      were able to control, over extended periods of time, the activity of genetically
      defined populations of neurons in vivo. New work using light-gated cation
      channels from green algae offers hope that this might soon be possible.

PMID- 16461262
TI  - Chromosome biology: the crux of the ring.
AB  - SMC proteins are key components of large ring-shaped chromosomal protein
      complexes, such as cohesin and condensin. New evidence supports the idea that
      these rings topologically encircle DNA. Hints also emerge as to what it may take
      for DNA to enter the ring.

PMID- 16461263
TI  - Rejecting arrogance.

PMID- 16461264
TI  - The vomeronasal system and pheromones.

PMID- 16461265
TI  - Cognitive neural prosthetics.

PMID- 16461266
TI  - Shortwave visual sensitivity in tree and flying squirrels reflects changes in
      lifestyle.

PMID- 16461267
TI  - Satiation gives krill that sinking feeling.

PMID- 16461268
TI  - Gliding motility: anticipating the next move with a molecular clock.
AB  - FrzS protein is important for normal social motility in myxobacteria, which
      includes periodic reversals in the direction of cell motion. Recent results show
      that cell reversal correlates with the migration of FrzS from the old leading
      pole of the cell to the new leading pole.

PMID- 16461269
TI  - Evolutionary genetics: choosing to evolve.
AB  - The evolution of mate choice is believed to be important in speciation. A recent
      experiment involving mating preference evolution in laboratory yeast populations
      supports theoretical predictions that this can occur without complete genetic
      isolation between populations, strengthening the case that ecological
      specialization as well as physical separation can lead to speciation.

PMID- 16461270
TI  - Nematode behavior: the taste of success, the smell of danger!
AB  - Through experience, the nematode worm Caenorhabditis elegans learns to
      distinguish high quality bacteria--food--from low quality or toxic bacteria.
      Increased release of the neurotransmitter serotonin onto identified interneurons
      determines whether C. elegans chooses to feed or leave.

PMID- 16461271
TI  - Tumor suppressors: control of signaling by endocytosis.
AB  - Genetic defects of the endosomal 'ESCRT' machinery in Drosophila have been found
      to cause loss of epithelial cell polarity, accompanied by overproliferation of
      mutant and adjacent wild-type cells. These results can be attributed to defective
      endocytosis of transmembrane proteins that control cell polarity and
      proliferation, including Crumbs and Notch.

PMID- 16461272
TI  - Oocyte-to-embryo transition: kinase cabal plots regime change.
AB  - The transition from oocyte to embryo is among the most enthralling events in
      developmental biology. Recent studies of this transition in the nematode
      Caenorhabditis elegans have revealed how conserved kinases administer the
      destruction of key oocyte meiotic regulators to create an embryo.

PMID- 16461273
TI  - Neuroimaging: perception at the brain's core.
AB  - Two new functional imaging studies have shown that activity in the lateral
      geniculate nucleus of the thalamus strongly reflects perceptual dominance during
      binocular rivalry, raising new questions about how subjective percepts arise in
      the brain.

PMID- 16461274
TI  - JAK/STAT signalling: STAT cannot play with Ken and Barbie.
AB  - Transcriptional responses to the activation of a signalling pathway are cell
      specific. New data show that the sequence-specific transcriptional repressors of
      the KEN/BCL-6 family play an important role in the selection of STAT targets in
      vertebrates and invertebrates, indicating that all STAT proteins may share this
      ancestral mechanism.

PMID- 16461275
TI  - Convergent evolution of receptors for protein import into mitochondria.
AB  - BACKGROUND: Mitochondria evolved from intracellular bacterial symbionts.
      Establishing mitochondria as organelles required a molecular machine to import
      proteins across the mitochondrial outer membrane. This machinery, the TOM
      complex, is composed of at least seven component parts, and its creation and
      evolution represented a sizeable challenge. Although there is good evidence that
      a core TOM complex, composed of three subunits, was established in the
      protomitochondria, we suggest that the receptor component of the TOM complex
      arose later in the evolution of this machine. RESULTS: We have solved by nuclear
      magnetic resonance the structure of the presequence binding receptor from the TOM
      complex of the plant Arabidopsis thaliana. The protein fold suggests that this
      protein, AtTom20, belongs to the tetratricopeptide repeat (TPR) superfamily, but
      it is unusual in that it contains insertions lengthening the helices of each TPR
      motif. Peptide titrations map the presequence binding site to a groove of the
      concave surface of the receptor. In vitro functional assays and peptide
      titrations suggest that the plant Tom20 is functionally equivalent to fungal and
      animal Tom20s. CONCLUSIONS: Comparison of the sequence and structure of Tom20
      from plants and animals suggests that these two presequence binding receptors
      evolved from two distinct ancestral genes following the split of the animal and
      plant lineages. The need to bind equivalent mitochondrial targeting sequences and
      to make similar interactions within an equivalent protein translocation machine
      has driven the convergent evolution of two distinct proteins to a common
      structure and function.

PMID- 16461276
TI  - TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila
      tauopathy model.
AB  - BACKGROUND: Previous studies have demonstrated reexpression of cell-cycle markers
      within postmitotic neurons in neurodegenerative tauopathies, including
      Alzheimer's disease (AD). However, the critical questions of whether cell-cycle
      activation is causal or epiphenomenal to tau-induced neurodegeneration and which
      signaling pathways mediate cell-cycle activation in tauopathy remain unresolved.
      RESULTS: Cell-cycle activation accompanies wild-type and mutant tau-induced
      neurodegeneration in Drosophila, and genetically interfering with cell-cycle
      progression substantially reduces neurodegeneration. Our data support a role for
      cell-cycle activation downstream of tau phosphorylation, directly preceding
      apoptosis. We accordingly show that ectopic cell-cycle activation leads to
      apoptosis of postmitotic neurons in vivo. As in AD, TOR (target of rapamycin
      kinase) activity is increased in our model and is required for neurodegeneration.
      TOR activation enhances tau-induced neurodegeneration in a cell cycle-dependent
      manner and, when ectopically activated, drives cell-cycle activation and
      apoptosis in postmitotic neurons. CONCLUSIONS: TOR-mediated cell-cycle activation
      causes neurodegeneration in a Drosophila tauopathy model, identifying TOR and the
      cell cycle as potential therapeutic targets in tauopathies and AD.

PMID- 16461277
TI  - Purified integrin adhesion complexes exhibit actin-polymerization activity.
AB  - BACKGROUND: Cell adhesion and motility are accomplished through a functional
      linkage of the extracellular matrix with the actin cytoskeleton via adhesion
      complexes composed of integrin receptors and associated proteins. To determine
      whether this linkage is attained actively or passively, we isolated integrin
      complexes from nonadherent hematopoietic cells and determined their influence on
      the polymerization of actin. RESULTS: We observed that alpha(V)beta3 complexes
      are capable of dramatically accelerating the rate of actin assembly, resulting in
      actin fibers tethered at their growing ends by clustered integrins. The ability
      to enhance actin polymerization was dependent upon Arg-Gly-Asp-ligand-induced
      beta3 tyrosine phosphorylation, agonist-induced cellular activation,
      sequestration of Diaphanous formins, and clustering of the receptor. CONCLUSIONS:
      These results suggest that adhesion complexes actively promote actin assembly
      from their cytosolic face in order to establish a mechanical linkage with the
      extracellular matrix.

PMID- 16461278
TI  - Regulation of sperm activation by SWM-1 is required for reproductive success of
      C. elegans males.
AB  - BACKGROUND: Sexual reproduction in animals requires the production of highly
      specialized motile sperm cells that can navigate to and fertilize ova. During
      sperm differentiation, nonmotile spermatids are remodeled into motile spermatozoa
      through a process known as spermiogenesis. In nematodes, spermiogenesis, or sperm
      activation, involves a rapid cellular morphogenesis that converts unpolarized
      round spermatids into polarized amoeboid spermatozoa capable of both motility and
      fertilization. RESULTS: Here we demonstrate, by genetic analysis and in vivo and
      in vitro cell-based assays, that the temporal and spatial localization of
      spermiogenesis are critical determinants of male fertility in C. elegans, a
      male/hermaphrodite species. We identify swm-1 as a factor important for male but
      not hermaphrodite fertility. We show that whereas in wild-type males, activation
      occurs after spermatids are transferred to the hermaphrodite, swm-1 mutants
      exhibit ectopic activation of sperm within the male reproductive tract. This
      ectopic activation leads to infertility by impeding sperm transfer. The SWM-1
      protein is composed of a signal sequence and two trypsin inhibitor-like domains
      and likely functions as a secreted serine protease inhibitor that targets two
      distinct proteases. CONCLUSIONS: These findings support a model in which (1)
      proteolysis acts as an important in vivo trigger for sperm activation and (2)
      regulating the timing of proteolysis-triggered activation is crucial for male
      reproductive success. Furthermore, our data provide insight into how a common
      program of gamete differentiation can be modulated to allow males to participate
      in reproduction in the context of a male/hermaphrodite species where the capacity
      for hermaphrodite self-fertilization has rendered them nonessential for progeny
      production.

PMID- 16461279
TI  - Tuning to natural stimulus dynamics in primary auditory cortex.
AB  - The amplitude and pitch fluctuations of natural soundscapes often exhibit "1/f
      spectra", which means that large, abrupt changes in pitch or loudness occur
      proportionally less frequently in nature than gentle, gradual fluctuations.
      Furthermore, human listeners reportedly prefer 1/f distributed random melodies to
      melodies with faster (1/f0) or slower (1/f2) dynamics. One might therefore
      suspect that neurons in the central auditory system may be tuned to 1/f dynamics,
      particularly given that recent reports provide evidence for tuning to 1/f
      dynamics in primary visual cortex. To test whether neurons in primary auditory
      cortex (A1) are tuned to 1/f dynamics, we recorded responses to random tone
      complexes in which the fundamental frequency and the envelope were determined by
      statistically independent "1/f(gamma) random walks," with gamma set to values
      between 0.5 and 4. Many A1 neurons showed clear evidence of tuning and responded
      with higher firing rates to stimuli with gamma between 1 and 1.5. Response
      patterns elicited by 1/f(gamma) stimuli were more reproducible for values of
      gamma close to 1. These findings indicate that auditory cortex is indeed tuned to
      the 1/f dynamics commonly found in the statistical distributions of natural
      soundscapes.

PMID- 16461280
TI  - The E3 ubiquitin ligase BIG BROTHER controls arabidopsis organ size in a dosage
      dependent manner.
AB  - Organ growth up to a species-specific size is tightly regulated in plants and
      animals. Final organ size is remarkably constant within a given species,
      suggesting that a species-specific size checkpoint terminates organ growth in a
      coordinated and timely manner. Phytohormones influence plant organ size, but
      their precise functions in size control are unclear because of their pleiotropic
      and complex developmental roles. The Arabidopsis transcription factors
      AINTEGUMENTA and JAGGED promote organ growth by maintaining cellular
      proliferation potential. Loss of the Antirrhinum transcription factor CINCINNATA
      causes leaf overgrowth, yet also leads to a highly abnormal leaf shape. Thus, no
      dedicated factor that limits the final size of plant organs has been isolated.
      Here, we identify the novel RING-finger protein BIG BROTHER (BB) as a repressor
      of plant organ growth. Small changes in BB expression levels substantially alter
      organ size, indicating a central regulatory role for BB in growth control.
      Recombinant BB protein has E3 ubiquitin-ligase activity that is essential for its
      in vivo function, suggesting that BB acts by marking cellular proteins for
      degradation. Our data indicate that plants limit the duration of organ growth and
      ultimately organ size by actively degrading critical growth stimulators.

PMID- 16461281
TI  - Experimental evolution of mating discrimination in budding yeast.
AB  - Assortative mating, when individuals of similar phenotypes mate, likely plays a
      key role in preventing gene flow during speciation. Reinforcement occurs when two
      previously geographically separated (allopatric) groups meet after having evolved
      partial postzygotic isolation; they are selected to evolve or enhance assortative
      mating to prevent costly intergroup matings that produce only maladaptive or
      sterile hybrids. Studies in Drosophila have shown that the genetic architectures
      of mating discrimination could differ significantly with or without
      reinforcement, suggesting that the evolution of assortative mating may be more
      complicated than expected. To study the evolution of assortative mating, we
      evolved mating discrimination in populations of the budding yeast, Saccharomyces
      cerevisiae. After 36 cycles of selection, these cells are five times more likely
      to mate with each other than to their ancestors, despite detectable one-way gene
      flow between the selected and reference populations. Several individual cultures
      evolved mating discrimination by changing their mating kinetics, with some mating
      more rapidly and others more slowly than the ancestral population. Genetic
      analysis indicates that multiple mutations have accumulated to produce the
      altered mating preference. Our results show that subtle details of mating
      behavior can play an important role in the evolution of reproductive isolation.

PMID- 16461283
TI  - Resveratrol prolongs lifespan and retards the onset of age-related markers in a
      short-lived vertebrate.
AB  - Resveratrol, a natural phytoalexin found in grapes and red wine, increases
      longevity in the short-lived invertebrates Caenorhabditis elegans and Drosophila
      and exerts a variety of biological effects in vertebrates, including protection
      from ischemia and neurotoxicity. Its effects on vertebrate lifespan were not yet
      known. The relatively long lifespan of mice, which live at least 2.5 years, is a
      hurdle for life-long pharmacological trials. Here, the authors used the short
      lived seasonal fish Nothobranchius furzeri with a maximum recorded lifespan of 13
      weeks in captivity. Short lifespan in this species is not the result of
      spontaneous or targeted genetic mutations, but a natural trait correlated with
      the necessity to breed in an ephemeral habitat and tied with accelerated
      development and expression of ageing biomarkers at a cellular level. Resveratrol
      was added to the food starting in early adulthood and caused a dose-dependent
      increase of median and maximum lifespan. In addition, resveratrol delays the age
      dependent decay of locomotor activity and cognitive performances and reduces the
      expression of neurofibrillary degeneration in the brain. These results
      demonstrate that food supplementation with resveratrol prolongs lifespan and
      retards the expression of age-dependent traits in a short-lived vertebrate.

PMID- 16461284
TI  - Cooperation between mitotic kinesins controls the late stages of cytokinesis.
AB  - Cell division is regulated by protein kinases of the Cdk, Polo, and Aurora
      families. Although it has long been established that temporal control is central
      to the coordinated action of these kinases, the importance of spatial regulation
      has only recently been appreciated and is still poorly understood. The kinesin-6
      family motor protein MKlp1 is a key regulator of cytokinesis and an ideal
      substrate for studying spatially regulated protein-phosphorylation events. MKlp1
      is negatively regulated by Cdk1 phosphorylation during metaphase and becomes
      activated in anaphase when cleavage-furrow assembly commences. Aurora B
      phosphorylates MKlp1 during anaphase and is required for its function in
      cytokinesis. Another kinesin-6 family motor, MKlp2, mediates the relocation of
      Aurora B from the centromeres to the central spindle at the onset of anaphase. We
      now demonstrate that this process is required for the phosphorylation of MKlp1 at
      S911, an Aurora B consensus site overlapping a bipartite nuclear localization
      sequence (NLS). MKlp1(S911A) targets to the central spindle but is prematurely
      imported into the nucleus and fails to support cytokinesis. Spatial restriction
      of Aurora B to the central spindle by MKlp2 therefore regulates MKlp1 during
      cytokinesis in human cells.

PMID- 16461282
TI  - Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans.
AB  - Wnt signaling regulates many aspects of metazoan development, including stem
      cells. In C. elegans, Wnt/MAPK signaling controls asymmetric divisions. A recent
      model proposed that the POP-1/TCF DNA binding protein works together with SYS
      1/beta-catenin to activate transcription of target genes in response to Wnt/MAPK
      signaling. The somatic gonadal precursor (SGP) divides asymmetrically to generate
      distal and proximal daughters of distinct fates: only its distal daughter
      generates a distal tip cell (DTC), which is required for stem cell maintenance.
      No DTCs are produced in the absence of POP-1/TCF or SYS-1/beta-catenin, and extra
      DTCs are made upon overexpression of SYS-1/beta-catenin. Here we report that POP
      1/TCF and SYS-1/beta-catenin directly activate transcription of ceh-22/nkx2.5
      isoforms in SGP distal daughters, a finding that confirms the proposed model of
      Wnt/MAPK signaling. In addition, we demonstrate that the CEH-22/Nkx2.5
      homeodomain transcription factor is a key regulator of DTC specification. We
      speculate that these conserved molecular regulators of the DTC niche in nematodes
      may provide insight into specification of stem cell niches more broadly.

PMID- 16461285
TI  - Cell cycle-dependent targeting of a kinesin at the plasma membrane demarcates the
      division site in plant cells.
AB  - Eukaryotic cells have developed different mechanisms to establish the division
      plane. In plants, the position is determined before the onset of mitosis by the
      preprophase band (PPB). This ring of microtubules surrounds the nucleus and
      disappears completely by prometaphase. An unknown marker is left behind by the
      PPB, providing the necessary spatial cues during cytokinesis. At the position of
      the PPB, cortical actin is removed or modified to generate an actin-depleted zone
      that was proposed to provide the structural means for phragmoplast guidance.
      Here, we identify a plasma membrane domain that emerges at the onset of mitosis
      and persists until the end of cytokinesis. The narrow band in the plasma membrane
      corresponds to the position of the PPB and is prevented from accumulation of a
      GFP-tagged kinesin GFP-KCA1; hence, it is called the KCA-depleted zone (KDZ). The
      KDZ demarcates the cortical division site independent from the mitotic
      cytoskeleton. Cell divisions in the absence of a KDZ resulted in misplaced cell
      plates, suggesting that the PPB transmits a signal to the plasma membrane
      required for correct cell plate guidance and vesicular targeting to the cortical
      division site.

PMID- 16461286
TI  - The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of
      beta1 integrins.
AB  - The small GTPase Arf6 has been shown to regulate the post-endocytic trafficking
      of a subset of membrane proteins, including beta1 integrins, and inhibition of
      Arf6 function impairs both cell adhesion and motility. The activity of Arf
      GTPases is regulated by a large family of guanine nucleotide exchange factors
      (GEFs). Arf-GEP100/BRAG2 is a GEF with reported specificity for Arf6 in vitro,
      but it is otherwise poorly characterized. Here we report that BRAG2 exists in two
      ubiquitously expressed isoforms, which we call BRAG2a and BRAG2b, both of which
      can activate Arf6 in vivo. Depletion of endogenous BRAG2 by siRNA leads to
      dramatic effects in the cell periphery; one such effect is an accumulation of
      beta1 integrin on the cell surface and a corresponding enhancement of cell
      attachment and spreading on fibronectin-coated substrates. In contrast, depletion
      of Arf6 leads to intracellular accumulation of beta1 integrin and reduced
      adhesion and spreading. These findings suggest that Arf6 regulates both
      endocytosis and recycling of beta1 integrins and that BRAG2 functions selectively
      to activate Arf6 during integrin internalization.

PMID- 16461288
TI  - Sex allocation conflict in ants: when the queen rules.
AB  - Insect societies are paramount examples of cooperation, yet they also harbor
      internal conflicts whose resolution depends on the power of the opponents. The
      male-haploid, female-diploid sex-determining system of ants causes workers to be
      more related to sisters than to brothers, whereas queens are equally related to
      daughters and sons. Workers should thus allocate more resources to females than
      to males, while queens should favor an equal investment in each sex. Female
      biased sex allocation and manipulation of the sex ratio during brood development
      suggest that workers prevail in many ant species. Here, we show that queens of
      Formica selysi strongly influenced colony sex allocation by biasing the sex ratio
      of their eggs. Most colonies specialized in the production of a single sex.
      Queens in female-specialist colonies laid a high proportion of diploid eggs,
      whereas queens in male-specialist colonies laid almost exclusively haploid eggs,
      which constrains worker manipulation. However, the change in sex ratio between
      the egg and pupae stages suggests that workers eliminated some male brood, and
      the population sex-investment ratio was between the queens' and workers'
      equilibria. Altogether, these data provide evidence for an ongoing conflict
      between queens and workers, with a prominent influence of queens as a result of
      their control of egg sex ratio.

PMID- 16461287
TI  - Dynamic anchoring of PKA is essential during oocyte maturation.
AB  - In the final stages of ovarian follicular development, the mouse oocyte remains
      arrested in the first meiotic prophase, and cAMP-stimulated PKA plays an
      essential role in this arrest. After the LH surge, a decrease in cAMP and PKA
      activity in the oocyte initiates an irreversible maturation process that
      culminates in a second arrest at metaphase II prior to fertilization. A-kinase
      anchoring proteins (AKAPs) mediate the intracellular localization of PKA and
      control the specificity and kinetics of substrate phosphorylation. Several AKAPs
      have been identified in oocytes including one at 140 kDa that we now identify as
      a product of the Akap1 gene. We show that PKA interaction with AKAPs is essential
      for two sequential steps in the maturation process: the initial maintenance of
      meiotic arrest and the subsequent irreversible progression to the polar body
      extruded stage. A peptide inhibitor (HT31) that disrupts AKAP/PKA interactions
      stimulates oocyte maturation in the continued presence of high cAMP. However,
      during the early minutes of maturation, type II PKA moves from cytoplasmic sites
      to the mitochondria, where it associates with AKAP1, and this is shown to be
      essential for maturation to continue irreversibly.

PMID- 16461289
TI  - Prognostic variables in patients with chronic myeloid leukemia treated with
      imatinib.

PMID- 16461290
TI  - Mechanism of thrombosis in essential thrombocythaemia.

PMID- 16461291
TI  - Of mice and mechanisms: identifying the role of complement in monoclonal antibody
      based immunotherapy.

PMID- 16461292
TI  - Further insights into multiple myeloma genetics.

PMID- 16461293
TI  - Skeletal tissue remodeling in multiple myeloma.

PMID- 16461294
TI  - Chemokine receptor expression in multiple myeloma.

PMID- 16461295
TI  - Effects of heparins on hemostatic properties of vascular endothelium.

PMID- 16461296
TI  - The feasibility of early discharge with oral antimicrobial therapy in low risk
      patients with febrile neutropenia following chemotherapy for hematologic
      malignancies.

PMID- 16461297
TI  - Chronic myeloid leukemia in 2006: a perspective.

PMID- 16461298
TI  - Not just clonal expansion of hematopoietic cells, but also activation of their
      progeny in the pathogenesis of myeloproliferative disorders.

PMID- 16461299
TI  - Molecular remission in chronic myeloid leukemia patients with sustained complete
      cytogenetic remission after imatinib mesylate treatment.
AB  - BACKGROUND AND OBJECTIVES: Imatinib mesylate induces a complete cytogenetic
      response (CCR) in many patients with chronic myeloid leukemia (CML). However, the
      ultimate goal of therapy for CML is complete elimination of Philadelphia
      chromosome positive cells or BCR-ABL rearrangements. We studied molecular
      responses in CML patients in CCR after imatinib treatment. DESIGN AND METHODS:
      Real-time quantitative reverse transcriptase polymerase chain reaction analysis
      were used to monitor BCR-ABL levels in 59 CCR patients. Negative results were
      confirmed by two different techniques performed in two different laboratories.
      Patients were considered in complete molecular remission if they had four
      undetectable analyses from two separate samples taken three months apart.
      RESULTS: The median follow-up was 41 months (17-53). The median BCR-ABL/ABL ratio
      at the time of CCR was 0.3 % (0-9.88). Patients were split into two groups: group
      A (n=43) comprised patients with a detectable BCR-ABL/ABL ratio throughout the
      follow-up and group B (n=16) included those with an undetectable level of BCR
      ABL/ABL (< 10(-5)) i.e. in complete molecular remission. No relapses were
      observed in group B, while 13 group A patients lost their CCR. The probability of
      losing CCR in this group was 33.2 % >+/-18.0. By Cox regression analysis the best
      factor for predicting the probability of achieving molecular remission was having
      a CCR at 6 months (p=0.038) or at 3 months (p=0.024). INTERPRETATION AND
      CONCLUSIONS: Molecular remission after imatinib treatment, i.e. BCR-ABL/ABL< 10-5
      in peripheral blood, is not a rare event, particularly in patients achieving CCR
      at 6 months.

PMID- 16461300
TI  - Increased platelet and leukocyte activation as contributing mechanisms for
      thrombosis in essential thrombocythemia and correlation with the JAK2 mutational
      status.
AB  - BACKGROUND AND OBJECTIVES: The mechanisms accounting for the increased risk of
      thrombosis in patients with essential thrombocythemia (ET) are not well known.
      The aim of the present study was to ascertain the role of platelet and leukocyte
      activation in the thrombosis of ET. DESIGN AND METHODS: The activation status of
      platelets and leukocytes was assessed by flow cytometry studies in 49 patients
      with ET (22 with previous thrombosis and 27 without a history of thrombosis) and
      in a group of age- and sex-matched healthy individuals. The assessment included
      platelet P-selectin expression (measured both at baseline and after stimulation
      with ADP, thrombin, arachidonic acid (AA), and collagen), platelet-neutrophil and
      platelet-monocyte complexes, determination of CD11b in the neutrophils and
      monocytes, and expression of tissue factor in the monocytes (mTF). The JAK2 V617F
      mutation was studied and correlated with platelet and leukocyte activation.
      RESULTS: As compared with controls, ET patients had significantly higher values
      of baseline P-selectin and thrombin- and AA-induced platelet P-selectin
      expression, as well as higher platelet-neutrophil and platelet-monocyte
      complexes, neutrophil CD11b expression and baseline mTF expression. Platelet P
      selectin, monocyte CD11b, and lipopolysaccharide-induced mTF expression was
      significantly higher in ET patients with a history of thrombosis than in patients
      without thrombosis. Patients with the JAK2 V617F mutation or thrombosis showed
      higher baseline and AA-induced platelet P-selectin expression than did those
      without thrombosis. INTERPRETATION AND CONCLUSIONS: These results would support a
      role for platelet and monocyte activation in the thrombosis of ET. In these
      patients, the presence of the JAK2 V617F mutation is associated with higher
      platelet activation.

PMID- 16461301
TI  - The role of complement in the therapeutic activity of rituximab in a murine B
      lymphoma model homing in lymph nodes.
AB  - BACKGROUND AND OBJECTIVES: We have set up a murine B lymphoma model stably
      expressing human CD20 and homing in lymph nodes in immunocompetent mice to study
      the mechanism of action of rituximab. DESIGN AND METHODS: The B lymphoma line
      38C13 was stably transduced with the human CD20 cDNA by retroviral infection and
      injected into syngeneic mice. RESULTS: The transduced 38C13-CD20(+) cells stably
      expressed human CD20 on 100% of cells. Rituximab alone did not inhibit 38C13
      CD20+ cell growth but relocalized the human CD20 into lipid rafts and induced
      complement-mediated lysis in vitro. Inoculation of 4x10(3) 38C13-CD20(+)
      intravenously into syngeneic mice led to the development of tumor masses in the
      spleen, bone marrow and lymph nodes, detectable from day 15 by polymerase chain
      reaction (PCR) analysis, and with a median survival of 21-24 days. Treatment with
      250 mg rituximab i.p. given 1-10 days after tumor inoculation cured 100% of
      animals, with disappearance of tumor documented by immunohistochemistry and PCR
      analysis. Depletion of both NK cells and neutrophils did not affect the
      therapeutic activity of rituximab in vivo. Similarly, removal of phagocytic
      macrophages using clodronate-liposomes did not modify the capacity of rituximab
      to control tumor growth. In contrast, the protective activity of the antibody was
      completely abolished after complement depletion with cobra venom factor.
      Complement was also required when cells were inoculated subcutaneously in nude
      mice. INTERPRETATION AND CONCLUSIONS: These data demonstrate that complement is
      required for the therapeutic activity of rituximab in vivo in a murine model of B
      cell lymphoma, independently of its localization in lymph nodes or
      subcutaneously.

PMID- 16461302
TI  - Identification of overexpressed genes in frequently gained/amplified chromosome
      regions in multiple myeloma.
AB  - BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is a malignancy characterized by
      clonal expansion of plasma cells. In 50% of the cases, the neoplastic
      transformation begins with a chromosomal translocation that juxtaposes the IGH
      gene locus to an oncogene. Gene copy number changes are also frequent in MM but
      less characterized than in other neoplasias. We aimed to characterize genes that
      are amplified and overexpressed in human myeloma cell lines (HMCL) to provide
      putative molecular targets for MM therapy. DESIGN AND METHODS: Nine HMCL were
      characterized by fluorescent in situ hybridization, comparative genomic
      hybridization (CGH) and cDNA microarrays for gene expression profiling and copy
      number changes. RESULTS: After defining the IGH-translocations present in the
      cell lines, we conducted expression-profiling analysis. Supervised analysis
      identified 166 genes with significantly different expression among the cell lines
      harboring MMSET/FGFR3 (4p16), MAF (16q) and CCND1 (11q13) rearrangements. Array
      CGH was then performed. Five chromosomes recurrently affected by
      gains/amplifications in primary samples and cell lines were analyzed in detail.
      Sixty amplified and overexpressed genes were found and 25 (42%) of them were only
      overexpressed when amplified; moreover, six showed a significant association
      between overexpression and gain/amplification. We also found co-amplification and
      overexpression for genes located within the same amplicons, such as MALT1 and
      BCL2. INTERPRETATION AND CONCLUSIONS: Parallel analysis of gene copy numbers and
      expression levels by cDNA microarray in MM allowed efficient identification of
      genes whose expression levels are elevated because of increased copy number. This
      is the first time that MALT1 and BCL2 have been shown to be overexpressed and
      amplified in MM.

PMID- 16461303
TI  - Inhibitory effects of osteoblasts and increased bone formation on myeloma in
      novel culture systems and a myelomatous mouse model.
AB  - BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) growth in the bone marrow is
      associated with increased osteoclast activity and a reduced number of
      osteoblasts. Experimental studies suggest that bone disease drives the
      progression of MM. Whereas those studies focused on the critical role of myeloma
      induced osteoclastogenesis in disease progression, little is known about the
      impact of osteoblasts and increased bone formation on MM. DESIGN AND METHODS: We
      investigated the effect of isolated osteoblasts and osteoclasts on survival and
      proliferation of primary MM plasma cells (PC) in co-cultures and triple-cultures,
      and tested the effect of mesenchymal stem cells (MSC) on bone mineral density and
      MM growth in myelomatous human bones of SCID-hu mice. RESULTS: Whereas
      osteoclasts promoted survival and proliferation of MM PC, osteoblasts supported
      or inhibited MM PC, depending on the source of the MM cells. In triple-cultures
      osteoblasts attenuated the effect of osteoclasts on MM PC in 18 of 24
      experiments. The anti-MM response to osteoblasts correlated with advanced
      clinical stage. Injection of MSC into myelomatous bones resulted in marked
      inhibition of tumor growth in three of nine experiments and stabilization of
      disease in two additional experiments. The anti-MM response of MSC was associated
      with increased human bone mineral density. Immunohistochemical analysis indicated
      that the MSC were well engrafted and, in responding mice, differentiated into
      osteogenic cells. INTERPRETATION AND CONCLUSIONS: MM PC from the majority of
      patients are susceptible to growth inhibition by osteoblasts; however, growth of
      MM PC from certain patients is accelerated by osteoblasts. In vivo, increased
      bone formation is associated with reduced myeloma burden.

PMID- 16461304
TI  - Clinical significance of chemokine receptor (CCR1, CCR2 and CXCR4) expression in
      human myeloma cells: the association with disease activity and survival.
AB  - BACKGROUND AND OBJECTIVES: The capacity of multiple myeloma (MM) cells to home to
      and reside in the bone marrow implies that they must be equipped with appropriate
      adhesion molecules and chemokine receptors to allow transendothelial migration.
      We and others have previously shown that human MM cells express at least three
      different chemokine receptors that are functionally involved in MM cell
      migration, i.e. CCR1, CCR2 and CXCR4. In this study, we analyzed the surface
      expression of these chemokine receptors on primary MM cells from bone marrow
      samples. DESIGN AND METHODS: Chemokine receptor expression was analyzed on bone
      marrow samples from a large population of patients (n=80) by flow cytometric
      analysis. The chemokine receptor expression profile was compared with clinical
      characteristics. Statistical significance was evaluated by Fisher's exact test.
      Survival curves were constructed using the Kaplan-Meier method. Cox regression
      analysis was used to determine the effect of chemokine receptor expression on
      survival. RESULTS: A heterogeneous expression pattern was observed for the three
      receptors tested. The chemokine receptor status (CRS) (i.e. no expression versus
      expression of at least one chemokine receptor), as well as expression of
      individual chemokine receptors was analyzed in relation to clinical and
      laboratory features and evaluated for prognostic significance. Chemokine receptor
      expression was significantly inversely correlated with disease activity: patients
      with active disease showed a significantly lower expression of CCR1, CCR2, as
      well as CXCR4 as compared to patients with non-active disease. Furthermore, the
      chemokine receptor expression profile correlated with serum beta2-microglobulin,
      C-reactive protein and hemoglobin. CRS, and the individual expressions of CCR1,
      CCR2 and CXCR4 in diagnostic bone marrow samples (n=70) correlated with survival.
      Multivariate analysis, using the Cox proportional hazard regression model,
      identified CRS, along with serum beta-microglobulin, as an independent prognostic
      factor. INTERPRETATION AND CONCLUSIONS: This study indicates that the chemokine
      receptor expression profile of MM cells correlates with disease status and
      survival of MM patients. This observation might reflect impaired chemoattraction
      and retention of MM cells within the bone marrow microenvironment, resulting in
      disease progression.

PMID- 16461305
TI  - Differential effect of the low-molecular-weight heparin, dalteparin, and
      unfractionated heparin on microvascular endothelial cell hemostatic properties.
AB  - BACKGROUND AND OBJECTIVES: Heparins, including unfractionated heparin (UFH) and
      low-molecular-weight heparins (LMWH), are glycosaminoglycans that are largely
      used as anti-thrombotic drugs. While the mechanisms of their anticoagulant
      actions in blood have been extensively studied, their effects on the hemostatic
      properties of the endothelium are still under investigation. The aim of this
      study was to compare the antithrombotic effects of a LMWH, i.e. dalteparin, with
      UFH on both microvascular (human microvascular endothelial cells [HMEC-1]) and
      macrovascular (human umbilical vein endothelial cells [HUVEC]) endothelial cells.
      DESIGN AND METHODS: Endothelial cells were incubated with dalteparin or UFH and
      exposed to an inflammatory stimulus (i.e. lipopolysaccharide [LPS]). The
      following parameters were evaluated: tissue factor (TF procoagulant activity,
      antigen and mRNA), tissue factor pathway inhibitor (TFPI), and thrombomodulin
      (TM). RESULTS: In HMEC-1 and HUVEC, both heparins inhibited LPS-induced
      endothelial cell TF expression. However, in HMEC-1, dalteparin was significantly
      more effective than UFH. Both heparins increased TFPI antigen release in HMEC-1
      and HUVEC. Dalteparin also reversed LPS-induced reduction of TM in HMEC-1, while
      UFH did not. INTERPRETATION AND CONCLUSIONS: These data show that both dalteparin
      and UFH suppress inflammatory-mediated TF expression and increase the
      anticoagulant properties of macro- and micro-vascular endothelial cells. However,
      dalteparin has significantly greater effects than UFH in the microvascular
      endothelium, a site that plays a central role in many processes involved in
      inflammation and thrombosis.

PMID- 16461306
TI  - The feasibility of early hospital discharge with oral antimicrobial therapy in
      low risk patients with febrile neutropenia following chemotherapy for hematologic
      malignancies.
AB  - BACKGROUND AND OBJECTIVES: It is now evident that patients experiencing febrile
      neutropenia induced by chemotherapy do not constitute a homogeneous group. With
      increasing accuracy it is now possible to identify low-risk patients for whom
      less intensive and more convenient treatment may be appropriate. DESIGN AND
      METHODS: In a cohort of such patients with hematologic malignancies, we
      prospectively validated the usefulness of the risk-index of the Multinational
      Association of Supportive Care in Cancer (MASCC) in identifying patients at low
      risk for the development of serious medical complications. Moreover, we studied
      the feasibility and safety of early discharge of these low-risk patients 24 hours
      after fever defervescence with subsequent oral antibiotic therapy. RESULTS: Of
      the 279 episodes of febrile neutropenia included, 105 (38%) had a MASCC risk
      index score indicating low risk. Serious complications were reported in
      connection with 111 (63%) high-risk and 16 (15%) low-risk episodes (p<0.0001).
      The risk-index identified low-risk patients with a specificity, sensitivity and
      positive predictive value of 87%, 58%, and 84%, respectively. A substantial
      proportion of the low-risk patients (36%) were considered ineligible for oral
      therapy, while the remaining 67 (64%) received oral antibiotic treatment
      following discharge from the hospital 24 hours after defervescence. Upon final
      evaluation, 64 of the discharged patients (95%) remained afebrile, only three
      required readmission and there was no mortality in this group. INTERPRETATION AND
      CONCLUSIONS: The MASCC risk-index is a valuable tool for identifying febrile
      neutropenic patients at low risk for complications. Oral antibiotic treatment
      following discharge from the hospital 24 hours after defervescence offers a safe
      and cost-effective alternative to the conventional management of carefully
      selected low-risk patients.

PMID- 16461307
TI  - Unrelated cord blood transplants in adults with hematologic malignancies.
AB  - BACKGROUND AND OBJECTIVES: We analyzed outcomes and risk factors after unrelated
      cord blood transplantation (CBT) in adults with hematologic malignancies. DESIGN
      AND METHODS: One hundred and seventy-one patients were transplanted after 1997.
      Their median age was 29 years (15-55), and the median follow-up time was 18
      months (1-71). Most patients had acute or chronic leukemia (n=142, 83%), 91 (53%)
      were transplanted in advanced phase and an autologous transplant had failed in 32
      (19%). Most patients (87%) received an HLA-mismatched cord blood unit with 1-2
      HLA disparities. At infusion, the median number of nucleated cells and CD34(+)
      cells was 2.1x10(7)/kg and 1x10(5)/kg, respectively RESULTS: The cumulative
      incidence of neutrophil recovery at day 60 was 72+/-3% with a median of 28 days
      (11-57). A higher neutrophil count and use of hematopoietic growth factors were
      independently associated with faster neutrophil recovery. The cumulative
      incidence of grade II-IV acute graft-versus-host disease was 32+/-4% and this
      complication was not associated with the number of HLA mismatches. The 2-year
      cumulative incidence of chronic graft-versus-host disease, transplant related
      mortality and relapse were 36+/-10%, 51+/-4% and 22+/-4%, respectively. At 2
      years, disease-free-survival for patients transplanted in early, intermediate and
      advanced phases of disease was 41+/-9%, 34+/-10% and 18+/-4%, respectively. In
      multivariate analyses, advanced disease status was an adverse factor for relapse
      and disease-free survival. INTERPRETATION AND CONCLUSIONS: Unrelated CBT is a
      clear alternative for adults with hematological malignancies lacking an HLA
      matched related or unrelated donor. The choice of units containing a higher
      neutrophil count and a policy of earlier transplantation are likely to provide
      better results.

PMID- 16461308
TI  - The limited value of methylmalonic acid, homocysteine and holotranscobalamin in
      the diagnosis of early B12 deficiency.
AB  - Treatment of B12 deficiency is important to prevent progressive neurological
      and/or hematologic disease but requires a secure diagnosis. The aim of this study
      was to evaluate second line tests of B12 status as prognostic indicators of a
      hematologic response to vitamin B12 therapy. Forty-nine patients referred with
      low, serum vitamin B12 concentrations were treated with intramuscular B12 and re
      assessed after 3 months. Methylmalonic acid, homocysteine, holotranscobalamin and
      neutrophil hypersegmentation index were measured before and after treatment.
      Before treatment 27/49 patients were anemic or macrocytic of whom 15 had a clear
      hematologic response. All the tests had a similar prognostic accuracy.
      Symptomatic improvement did not correlate with hematologic response.
      Supplementary tests of vitamin B12 status were not significantly better than
      total serum B12 concentration as predictors of a hematologic response to vitamin
      B12 therapy.

PMID- 16461309
TI  - The role of serial BCR-ABL transcript monitoring in predicting the emergence of
      BCR-ABL kinase mutations in imatinib-treated patients with chronic myeloid
      leukemia.
AB  - BCR-ABL kinase mutations may confer resistance to imatinib in patients with
      chronic myeloid leukemia (CML), and may predict a poor outcome. We investigated
      whether rises in BCR-ABL transcript levels predicted mutation development in 82
      CML patients receiving imatinib. Eleven mutations were detected in 10 patients. A
      single 2-fold or greater rise in BCR-ABL transcript did not predict mutations.
      However, a mutation was detectable in five of six cases with progressively rising
      levels of transcripts. In contrast, consecutive rises were not seen in any of 33
      stable responders. Rising BCR-ABL transcript levels can identify patients who
      developBCR-ABLmutations. A serial rise is more reliable than a single rise.

PMID- 16461310
TI  - The putative role of transforming viruses in childhood acute lymphoblastic
      leukemia.
AB  - Epidemiological evidence suggests that infection is involved in the etiology of
      common acute lymphoblastic leukemia, either by stimulating an inappropriate
      immune response or in the form of a classical transforming agent. In an attempt
      to elucidate the role that infection is playing in this disease, we used
      representational difference analysis (RDA) to examine tumor samples for the
      presence of exogenous genomes. Twenty RDA experiments were carried out, using
      four different restriction enzymes, but no exogenous sequences were identified
      within leukemic cells. These results suggest that it is unlikely that a single,
      direct transforming agent is involved in the pathogenesis of common acute
      lymphoblastic leukemia.

PMID- 16461311
TI  - Differential dynamics of Epstein-Barr virus in individuals infected with human
      immunodeficiency virus-1 receiving intermittent interleukin-2 and antiretroviral
      therapy.
AB  - Interleukin-2 (IL-2) increases circulating CD4(+) lymphocytes in patients
      infected with human immunodeficiency virus-1. We studied Epstein-Barr virus (EBV)
      dynamics in 40 patients treated with antiretroviral therapy (ART) plus different
      IL-2 regimens. EBV-DNA tended to increase in both peripheral blood cells and
      plasma after continous infusion followed by intermittent subcutaneous high-dose
      IL-2, while EBV-DNA decreased in cells (p=0.0078) and disappeared in plasma after
      intermittent subcutaneous low-dose IL-2. Over 12 months, the dynamics of EBV
      differed between the two groups both in cells (p=0.0184) and plasma (p=0.0114).
      Thus, as a function of dose, IL-2 therapy may significantly affect the dynamics
      of EBV infection.

PMID- 16461312
TI  - The effects of the histone deacetylase inhibitor valproic acid on cell cycle,
      growth suppression and apoptosis in multiple myeloma.
AB  - The aim of this study was to evaluate the effects of valproic acid (VPA), as a
      histone deacetylase inhibitor, on myeloma cell lines and on sorted human bone
      marrow multiple myeloma cells. VPA induced accumulation of acetylated histones,
      potently inhibited proliferation in a dose-dependent manner and induced apoptosis
      in all myeloma cell lines tested as well as in sorted primary multiple myeloma
      cells. Cell cycle analysis indicated an arrest in G0/1 phase in response to VPA.
      Accumulation of p21 and reduced levels of cyclin D1 were detected. The production
      of vascular endothelial growth factor was significantly inhibited by VPA. These
      results provide the framework for clinical trials.

PMID- 16461313
TI  - Primary treatment with pulsed melphalan, dexamethasone and thalidomide for
      elderly symptomatic patients with multiple myeloma.
AB  - Fifty patients with multiple myeloma >or=75 years of age received primary
      treatment with melphalan (M) 8 mg/m(2) on days 1-4, dexamethasone (D) 12 mg/m2 on
      days 1-4 and 17-20 and thalidomide (T) 300 mg at bedtime on days 1-4 and 17-20.
      This regimen was repeated every 5 weeks for three courses. Patients without
      evidence of disease progression received nine additional courses of MDT, but
      without DT on days 17-20, every 5 weeks. Sixty-two percent of patients achieved a
      partial response and 10% a complete response. The median time to response was 2
      months. The median time to progression for all patients was 21.2 months. Deep
      venous thrombosis and peripheral neuropathy each occurred in 9% of patients.

PMID- 16461314
TI  - Topical prophylaxis of conjunctivitis induced by high-dose cytosine arabinoside.
AB  - We investigated the efficacy of dexamethasone plus diclofenac eye drops as
      prophylaxis for conjunctivitis induced by high-dose (HD) cytarabine (Ara-C).
      Sixty patients were randomized to receive either dexamethasone (group A, n=29) or
      dexamethasone plus diclofenac (group B, n=31). Conjunctivitis was experienced by
      13/29 (45%) patients in group A, and 4/31 (13%) patients in group B (p<or=0.009).
      Twelve out of 13 patients in group A who developed ocular toxicity had grade 2-3
      conjunctivitis whereas only one of four patients affected in group B experienced
      a similar grade of conjunctivitis. The incidence and severity of HD Ara-C-induced
      conjunctivitis are significantly reduced by combined dexamethasone/ diclofenac
      prophylaxis.

PMID- 16461315
TI  - Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic
      stem cell transplantation: incidence, predictors and outcome.
AB  - Scleroderma may be one of the most severe forms of chronic graft-versus-host
      disease (GVHD). We retrospectively evaluated its incidence, predictor variables
      and outcome in 133 patients who survived at least 4 months after allogeneic
      hematopoietic stem cell transplantation. The 5-year cumulative incidence was
      15.5% in patients with chronic GVHD. The generalized form had a progressive
      course despite immunosuppressive therapy. Eosinophilia, autoimmune markers, and
      previous skin involvement by chronic GVHD with disorders of pigmentation were
      significantly associated with an increased probability of developing scleroderma.

PMID- 16461316
TI  - The role of the G6PD AEth376G/968C allele in glucose-6-phosphate dehydrogenase
      deficiency in the seerer population of Senegal.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in tropical Sub
      Saharan countries. The allele most frequently associated with G6PD deficiency in
      this a region is G6PD 376G/202A. Here, we show that, the prevalence of G6PD
      deficiency is 12% in the Sereer ethnic group from Senegal ant that the 376G/968C
      genotype is predominant; the frequency of the 376G/202A genotype is very low in
      this ethnic group.

PMID- 16461317
TI  - The usefulness of serum transferrin receptor for discriminating iron deficiency
      without anemia in children.
AB  - We determined serum transferrin receptor (sTfR), serum erythropoietin and
      hematologic and biochemical iron parameters in 251 healthy children. The levels
      of sTfR were significantly higher in children with storage iron deficiency but
      had a poor sensivity for recognizing iron deficiency without anemia. When
      ferritin values cannot accurately demonstrate the iron deficiency in children,
      the sTfR/ferritin ratio or sTfR-log ferritin is recommended to discriminate iron
      deficiency in the absence of anemia.

PMID- 16461318
TI  - Molecular characterization of five Portuguese patients with pyrimidine 5'
      nucleotidase deficient hemolytic anemia showing three new P5'N-I mutations.
AB  - Four different gene mutations were identified in five unrelated Portuguese
      patients with pyrimidine 5'-nucleotidase type I (P5'N-I) deficient chronic
      hemolytic anemia. Mutations 502G-->C (168Gly-->Arg), 773T-->C (258Ile-->Thr) and
      the insertion of an Alu element in exon 9, leading to skipping of this exon in
      the mRNA transcript, are newly described mutations whereas mutation 425T-->C
      (142Leu-->Pro) has been previously reported.

PMID- 16461319
TI  - The involvement of cellular proliferation status in the expression of the human
      proto-oncogene DEK.
AB  - The role of the DEK protein, involved in the leukemia-associated fusion protein
      DEK-CAN, is not yet known. In this study, we show a higher expression of DEK mRNA
      in immature cells than in mature cells. Furthermore, a correlation between DEK
      expression and cell proliferation was demonstrated, suggesting that DEK plays a
      role in the proliferation of hematopoietic cells and raising the question of
      whether the DEK-CAN fusion protein might perturb regulation of proliferation in
      leukemic cells.

PMID- 16461320
TI  - Prognostic value of quantitative analysis of WT1 gene transcripts in adult acute
      lymphoblastic leukemia.
AB  - We quantified Wilm's tumor gene (WT1) using a real time quantitative polymerase
      chain reaction in 20 adult patients with acute lymphoblastic leukemia at
      presentation. A WT1 level greater than 906 (median value for the whole series)
      was a significant predictor of a poor disease-free and overall survival in uni-
      and multivariate analyses.

PMID- 16461321
TI  - Rituximab plus chemotherapy in children with relapsed or refractory CD20-positive
      B-cell precursor acute lymphoblastic leukemia.
AB  - We treated three children with relapsed or refractory CD20 positive B-cell
      precursor acute lymphoblastic leukemia with rituximab in combination with
      chemotherapy, which produced a decreasing or persistent low positive minimal
      residual disease load. Two children subsequently underwent allogeneic stem cell
      transplantation and remain in complete remission at days +399 and +332.

PMID- 16461322
TI  - Incidence of monoclonal B-cell disease in siblings of patients with multiple
      myeloma.
AB  - We observed clustering of monoclonal B-cell disease in siblings being screened as
      allogeneic donors for patients with multiple myeloma (MM) scheduled for stem cell
      transplantation (SCT). Of 134 asymptomatic donors, the incidence of monoclonal B
      cell disease was 8/84 in siblings and 1/50 in matched unrelated donors. From an
      analysis of five MM families scheduled for allogeneic SCT, monoclonal B-cell
      disease was detected in 8/27 siblings.

PMID- 16461323
TI  - Anti-interleukin-2 receptor antibody (daclizumab) treatment of corticosteroid
      refractory autoimmune thrombocytopenic purpura.
AB  - We administered daclizumab, a humanized monoclonal anti-interleukin-2 receptor
      (IL-2R) antibody, to 11 patients with corticosteroid-refractory autoimmune
      thrombocytopenic purpura (AITP) every 2 weeks for five treatments. Of nine
      evaluable patients, one individual experienced a partial response. Lymphocyte
      phenotyping by flow cytometry indicated post-treatment binding of IL-2Ra by
      daclizumab in all patients. Mid-study serum soluble IL-2R levels in all patients
      increased 4-15 -fold over baseline values (p=0.004). Despite these measurable
      immunologic effects, blockade of the IL-2/IL-2R axis did not effectively abrogate
      the autoimmune response in this group of patients with corticosteroid-refractory
      AITP.

PMID- 16461324
TI  - Association of estrogen receptor-alpha genepolymorphisms with venous thrombosis.
AB  - XbaI and PvuII polymorphisms of the estrogen receptor-alpha gene (ERalpha) have
      been associated with several multifactorial diseases. We studied the distribution
      of ERalpha polymorphisms in patients with deep vein thrombosis. PvuII PP and XbaI
      XX genotypes may be associated with an approximately 2-fold increased DVT risk of
      deep vein thrombosis in men.

PMID- 16461325
TI  - Intravenous thrombolytic therapy in patients with phlegmasia caerulea dolens.
AB  - In a prospective study, nine patients with phlegmasia caerulea dolens (PCD)
      related to iliac occlusive thrombosis were treated with intravenous thrombolysis.
      After thrombolysis, despite no significant improvement in the Marder score value,
      progression to venous gangrene, major hemorrhage or death was not observed and no
      amputation was needed. Intravenous thrombolysis should be seriously considered in
      patients with PCD.

PMID- 16461326
TI  - The origin of epithelial neoplasms after allogeneic stem cell transplantation.
AB  - We analyzed five women, who have developed epithelial neoplasms after sex
      mismatched stem cell transplants. Using in situ hybridization for sex chromosome
      specific DNA probes and immunohistochemistry we identified the origin of the
      tumor cells. We conclude that none of the non-hematologic malignancies was of
      donor origin.

PMID- 16461327
TI  - Targeted marrow irradiation with radioactively labeled anti-CD66 monoclonal
      antibody prior to allogeneic stem cell transplantation for patients with
      leukemia: results of a phase I-II study.
AB  - We treated 20 adult patients with a (188) Re-labeled anti-CD66 antibody (mean
      marrow dose 13.3 Gy) prior to allogeneic stem cell transplantation for
      Philadelphia chromosome-positive acute lymphoblastic leukemia or advanced chronic
      myeloid leukemia. The intensified conditioning was not associated with increased
      non-relapse mortality. No reduction in the incidence of relapse was observed in
      the context of a T-cell depleted graft (4-year overall survival: 29%).

PMID- 16461328
TI  - Breakthrough fungemia caused by fluconazole-resistant Candida albicans with
      decreased susceptibility to voriconazole in patients with hematologic
      malignancies.
AB  - A 7-year retrospective analysis of candidemia in patients with hematologic
      malignancies demonstrated that ten patients, who received itraconazole and
      fluconazole during neutropenia, developed breakthrough fungemia caused by
      fluconazole-resistant Candida albicans (C. albicans) with decreased
      susceptibility to voriconazole. Eight of these ten patients died of candidemia
      despite amphotericin B administration. Karyotype analysis of C. albicans isolates
      revealed that all isolates were genetically unrelated? Our findings suggest that
      blood isolates of C. albicans in neutropenic patients receiving azoles could be
      azole cross-resistant, and that the patients should be treated by other
      antifungals such as echinocandins.

PMID- 16461329
TI  - Nitric-oxide synthase output state. Design and properties of nitric-oxide
      synthase oxygenase/FMN domain constructs.
AB  - Mammalian nitric-oxide synthases are large modular enzymes that evolved from
      independently expressed ancestors. Calmodulin-controlled isoforms are signal
      generators; calmodulin activates electron transfer from NADPH through three
      reductase domains to an oxygenase domain. Structures of the reductase unit and
      its homologs show FMN and FAD in contact but too isolated from the protein
      surface to permit exit of reducing equivalents. To study states in which FMN/heme
      electron transfer is feasible, we designed and produced constructs including only
      oxygenase and FMN binding domains, eliminating strong internal reductase complex
      interactions. Constructs for all mammalian isoforms were expressed and purified
      as dimers. All synthesize NO with peroxide as the electron donor at rates
      comparable with corresponding oxygenase constructs. All bind cofactors nearly
      stoichiometrically and have native catalytic sites by spectroscopic criteria.
      Modest differences in electrochemistry versus independently expressed heme and
      FMN binding domains suggest interdomain interactions. These interactions can be
      convincingly demonstrated via calmodulin-induced shifts in high spin ferriheme
      EPR spectra and through mutual broadening of heme and FMNH. radical signals in
      inducible nitric-oxide synthase constructs. Blue neutral FMN semiquinone can be
      readily observed; potentials of one electron couple (in inducible nitric-oxide
      synthase oxygenase FMN, FMN oxidized/semiquinone couple = +70 mV, FMN
      semiquinone/hydroquinone couple = -180 mV, and heme = -180 mV) indicate that FMN
      is capable of serving as a one electron heme reductant. The construct will serve
      as the basis for future studies of the output state for NADPH derived reducing
      equivalents.

PMID- 16461330
TI  - Hemoglobin degradation in malaria-infected erythrocytes determined from live cell
      magnetophoresis.
AB  - During intra-erythrocytic development, malaria trophozoites digest hemoglobin,
      which leads to parasite growth and asexual replication while accumulating toxic
      heme. To avoid death, the parasite synthesizes insoluble hemozoin crystals in the
      digestive vacuole through polymerization of beta-hematin dimers. In the process,
      the heme is converted to a high-spin ferriheme whose magnetic properties were
      studied as early as 1936 by Pauling et al. Here, by magnetophoretic cell motion
      analysis, we provide evidence for a graduated increase of live cell magnetic
      susceptibility with developing blood-stage parasites, compatible with the
      increase in hemozoin content and the mechanism used by P. falciparum to avoid
      heme toxicity. The measured magnetophoretic mobility of the erythrocyte infected
      with a late-stage schizont form was m = 2.94 x 10(-6) mm3 s/kg, corresponding to
      the net volume magnetic susceptibility (relative to water) of Deltachi = 1.80 x
      10(-6), significantly higher than that of the oxygenated erythrocyte (-0.18x10(
      6)) but lower than that of the fully deoxygenated erythrocyte (3.33x10(-6)). The
      corresponding fraction of hemoglobin converted to hemozoin, calculated based on
      the known magnetic susceptibilities of hemoglobin heme and hemozoin ferriheme,
      was 0.50, in agreement with the published biochemical and crystallography data.
      Magnetophoretic analysis of live erythrocytes could become significant for
      antimalarial drug susceptibility and resistance determination.

PMID- 16461331
TI  - Vascular tenascin-C regulates cardiac endothelial phenotype and
      neovascularization.
AB  - Microenvironmental cues mediate postnatal neovascularization via modulation of
      endothelial cell and bone marrow-derived endothelial progenitor cell (EPC)
      activity. Numerous signals regulate the activity of both of these cell types in
      response to vascular injury, which suggests that parallel mechanisms regulate
      angiogenesis in the vascular beds of both the heart and bone marrow. To identify
      mediators of such shared pathways, in vivo bone marrow/cardiac phage display
      biopanning was performed and led to the identification of tenascin-C as a
      candidate protein. Functionally, tenascin-C inhibits cardiac endothelial cell
      spreading and enhances migration in response to angiogenic growth factors.
      Analysis of human coronary thrombi revealed tenascin-C protein expression
      colocalized with the endothelial cell/EPC marker Tie-2 in intrathrombi vascular
      channels. Immunostains in the rodent heart demonstrated that tenascin-C also
      colocalizes with EPCs homing to sites of cardiac angiogenic induction. To
      determine the importance of tenascin-C in cardiac neovascularization, we used an
      established cardiac transplantation model and showed that unlike wild-type mice,
      tenascin-C-/- mice fail to vascularize cardiac allografts. This demonstrates for
      the first time that tenascin-C is essential for postnatal cardiac angiogenic
      function. Together, our data highlight the role of tenascin-C as a
      microenvironmental regulator of cardiac endothelial/EPC activity.

PMID- 16461333
TI  - Quality of systematic reviews used in guidelines for oncology practice.
AB  - BACKGROUND: Systematic reviews are an important tool for developing clinical
      recommendations. Those of high quality assure a good level of confidence on the
      strength of the recommendations. METHODS: A QUOROM-based checklist was applied to
      the reviews cited in a sample of guidelines on breast and colon cancer prevention
      and therapy. The checklist provided a weight for each criterion and a total
      quality score. Each review was independently evaluated by two reviewers;
      disagreements were solved by consensus. RESULTS: Eighty reviews (96%) were
      retrieved and evaluated; 36 focused on breast, and 44 on colorectal cancer.
      Twenty-three reviews (29%) did not match the definition of systematic review. In
      17 (21%) the searching methods were unclear or described elsewhere. Forty (50%)
      were systematic. Not systematic, low and very low quality reviews accounted for
      70% of the total. No review obtained the A+ class score; only 5 (6%) the A- and 7
      (9%) the B+. CONCLUSIONS: The results of this assessment provide a sober picture
      of the quality of the sources used to build guidelines. Oncologists should be
      aware that they could be relying on poor underlying documents. Writing groups
      should be aware of methodological problems, and should consult the existing
      manuals for the preparation of guidelines.

PMID- 16461332
TI  - Assessment of lymphocyte subpopulations and cytokine secretion in children
      exposed to arsenic.
AB  - Exposure of several human populations to arsenic has been associated with a high
      incidence of detrimental dermatological and carcinogenic effects. To date,
      studies examining the immunotoxic effects of arsenic in humans, and specifically
      in children, are lacking. Therefore, we evaluated several parameters of
      immunological status in a group of children exposed to arsenic through their
      drinking water. Peripheral blood mononuclear cells (PBMCs) of 90 children (6 to
      10 years old) were collected. Proportions of lymphocyte subpopulations, PBMC
      mitogenic proliferative response, and urinary arsenic levels were evaluated.
      Increased urine arsenic levels were associated with a reduced proliferative
      response to phytohemaglutinin (PHA) stimulation (P=0.005), CD4 subpopulation
      proportion (P=0.092), CD4/CD8 ratio (P=0.056), and IL-2 secretion levels
      (P=0.003). Increased arsenic exposure was also associated with an increase in GM
      CSF secretion by mononucleated cells (P=0.000). We did not observe changes in
      CD8, B, or NK cell proportions, nor did we observe changes in the secretion of IL
      4, IL-10, or IFN-gamma by PHA-activated PBMCs. These data indicate that arsenic
      exposure could alter the activation processes of T cells, such that an
      immunosuppression status that favors opportunistic infections and carcinogenesis
      is produced together with increased GM-CSF secretion that may be associated with
      chronic inflammation.

PMID- 16461334
TI  - Suppression of polyglutamine-induced toxicity in cell and animal models of
      Huntington's disease by ubiquilin.
AB  - Expanded polyglutamine (polyQ) tracts are associated with the induction of
      protein aggregation and cause cytotoxicity in nine different neurodegenerative
      disorders. Here, we report that ubiquilin suppresses polyQ-induced protein
      aggregation and toxicity in cells and in an animal model of Huntington's disease.
      Overexpression of ubiquilin in HeLa cells and primary neurons reduced aggregation
      of polyQ-containing proteins and cell death induced by overexpression of a green
      fluorescent protein (GFP)-huntingtin fusion protein containing 74 polyQ repeats
      [GFP-Htt(Q74)], in a dose-dependent manner. Moreover, overexpression of ubiquilin
      suppressed oxidative stress-induced cell death in HeLa cell lines stably
      expressing GFP-Htt(Q74). In contrast, knockdown of ubiquilin expression in these
      cell lines was associated with increases in DNA fragmentation, caspase
      activation, GFP-fusion protein aggregation, and cell death. Caenorhabditis
      elegans lines expressing GFP-Htt fusion proteins in body wall muscle displayed a
      polyQ repeat length-dependent decrease in body movement compared with wild-type
      animals. RNA interference of the C. elegans ubiquilin gene exacerbated the
      motility defect, whereas overexpression of ubiquilin prevented, and could rescue,
      loss of worm movement induced by overexpression of GFP-Htt(Q55). These results
      suggest that ubiquilin might be a novel therapeutic target for treating polyQ
      diseases.

PMID- 16461335
TI  - Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1
      patients.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. KIT and PDGFRA activating mutations are the oncogenic
      mechanisms in most sporadic GISTs. In addition to sporadic occurrences, GISTs are
      increasingly being recognized in association with neurofibromatosis type 1 (NF1),
      yet the underlying pathogenic mechanism remains elusive. To gain an insight into
      the mechanisms underlying GIST formation in NF1 patients, we studied seven GISTs
      from three NF1 patients with a combination of different techniques: mutation
      analysis (KIT, PDGFRA and NF1), western blotting, array CGH and ex vivo imatinib
      response experiments. We demonstrate that (i) the NF1-related GISTs do not have
      KIT or PDGFRA mutations, (ii) the molecular event underlying GIST development in
      this patient group is a somatic inactivation of the wild-type NF1 allele in the
      tumor and (iii) inactivation of neurofibromin is an alternate mechanism to
      (hyper) activate the MAP-kinase pathway, while the JAK-STAT3 and PI3K-AKT
      pathways are less activated in NF1-related GIST compared with sporadic GISTs. In
      conclusion, we report for the first time the molecular pathogenesis of GISTs in
      NF1 individuals and demonstrate that this type of tumor clearly belongs to the
      spectrum of clinical symptoms in NF1.

PMID- 16461336
TI  - An exon skipping-associated nonsense mutation in the dystrophin gene uncovers a
      complex interplay between multiple antagonistic splicing elements.
AB  - A nonsense mutation c.4250T>A (p.Leu1417X) in the dystrophin gene of a patient
      with an intermediate phenotype of muscular dystrophy induces partial in-frame
      skipping of exon 31. On the basis of UV cross-linking assays and pull-down
      analysis, we present evidence that the skipping of this exon is because of the
      creation of an exonic splicing silencer, which acts as a highly specific binding
      site (UAGACA) for a known repressor protein, hnRNP A1. Recombinant hnRNP A1
      represses exon inclusion both in vitro and in vivo upon transient transfection of
      C2C12 cells with Duchenne muscular dystrophy (DMD) minigenes carrying the
      c.4250T>A mutation. Furthermore, we identified a downstream splicing enhancer in
      the central region of exon 31. This region functions as a Tra2beta-dependent
      exonic splicing enhancer (ESE) in vitro when inserted into a heterologous
      splicing reporter, and deletion of the ESE showed that incorporation of exon 31
      depends on the Tra2beta-dependent enhancer both in the wild-type and mutant
      context. We conclude that dystrophin exon 31 contains juxtaposed sequence motifs
      that collaborate to regulate exon usage. This is the first elucidation of the
      molecular mechanism leading to exon skipping in the dystrophin gene and allowing
      the occurrence of a milder phenotype than the expected DMD phenotype. The
      knowledge of which cis-acting sequence within an exon is important for its
      definition will be essential for the alternative gene therapy approaches based on
      modulation of splicing to bypass DMD-causing mutations in the endogenous
      dystrophin gene.

PMID- 16461337
TI  - The bradykinin beta 2 receptor (BDKRB2) and endothelial nitric oxide synthase 3
      (NOS3) genes and endurance performance during Ironman Triathlons.
AB  - We have previously shown that the insertion allele of the angiotensin-converting
      enzyme (ACE) gene was over-represented in the fastest South-African-born
      finishers of the South African Ironman Triathlons. As ACE is a component of the
      skeletal muscle kallikrein-kinin system (KKS), the aim of this study is to
      determine if there are any further associations between polymorphisms within the
      BDKRB2 and NOS3 genes, which encode for the KKS components, bradykinin beta(2)
      receptor and nitric oxide synthase, respectively, and ultra-endurance performance
      during the Ironman Triathlons. Four-hundred and forty-three male Caucasian
      triathletes who completed the 2000 and/or 2001 South African Ironman Triathlons
      and 203 healthy Caucasian male control subjects were genotyped for the functional
      -9/+9 polymorphism within exon 1 of the BDKRB2 gene and the G894T NOS3 gene
      polymorphisms. The BDKRB2 -9/-9 genotype occurred at a significantly higher
      frequency when the triathlete group (27.0%) was compared with the control group
      (19.3%, P=0.035). When divided into tertiles, there was also a significant linear
      trend for the NOS3 GG genotype distribution among the fastest (35.0%), middle
      (40.4%) and slowest (46.9%) finishers (P=0.039). The overall finishing times of
      the triathletes with an NOS3 GG genotype together with a BDKRB2 +9 allele were
      significantly slower than those with other genotype combinations (P=0.001). The
      NOS3/BDKRB2 genotype (beta=-0.150, B=-31.48, P=0.002), together with body mass
      index and age, accounted for 14.6% of the variance in the overall race time for
      the triathlon. In conclusion, both the NOS3 and BDKRB2 genes are associated with
      the actual performance during the Ironman Triathlons.

PMID- 16461339
TI  - ATM regulates ATR chromatin loading in response to DNA double-strand breaks.
AB  - DNA double-strand breaks (DSBs) are among the most deleterious lesions that can
      challenge genomic integrity. Concomitant to the repair of the breaks, a rapid
      signaling cascade must be coordinated at the lesion site that leads to the
      activation of cell cycle checkpoints and/or apoptosis. In this context, ataxia
      telangiectasia mutated (ATM) and ATM and Rad-3-related (ATR) protein kinases are
      the earliest signaling molecules that are known to initiate the transduction
      cascade at damage sites. The current model places ATM and ATR in separate
      molecular routes that orchestrate distinct pathways of the checkpoint responses.
      Whereas ATM signals DSBs arising from ionizing radiation (IR) through a Chk2
      dependent pathway, ATR is activated in a variety of replication-linked DSBs and
      leads to activation of the checkpoints in a Chk1 kinase-dependent manner.
      However, activation of the G2/M checkpoint in response to IR escapes this
      accepted paradigm because it is dependent on both ATM and ATR but independent of
      Chk2. Our data provides an explanation for this observation and places ATM
      activity upstream of ATR recruitment to IR-damaged chromatin. These data provide
      experimental evidence of an active cross talk between ATM and ATR signaling
      pathways in response to DNA damage.

PMID- 16461338
TI  - Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2,
      7, 8, and 9 to stimulate polyvalent immunity.
AB  - The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most
      effective vaccines available, with a 65-yr history of use in >400 million people
      globally. Despite this efficacy, there is presently no information about the
      immunological mechanisms by which YF-17D acts. Here, we present data that suggest
      that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells
      (DCs) to elicit a broad spectrum of innate and adaptive immune responses.
      Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to
      elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon
      alpha. Interestingly, the resulting adaptive immune responses are characterized
      by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T
      cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2
      balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1
      cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF
      17D. Together, these data enhance our understanding of the molecular mechanism of
      action of YF-17D, and highlight the potential of vaccination strategies that use
      combinations of different TLR ligands to stimulate polyvalent immune responses.

PMID- 16461340
TI  - Killer cell lectin-like receptor G1 binds three members of the classical cadherin
      family to inhibit NK cell cytotoxicity.
AB  - Killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor expressed
      on subsets of natural killer (NK) cells and T cells, for which no endogenous
      ligands are known. Here, we show that KLRG1 binds three of the classical
      cadherins (E-, N-, and R-), which are ubiquitously expressed in vertebrates and
      mediate cell-cell adhesion by homotypic or heterotypic interactions. By
      expression cloning using the mouse KLRG1 tetramer as a probe, we identified human
      E-cadherin as a xenogeneic ligand. We also identified a syngeneic interaction
      between mouse KLRG1 and mouse E-cadherin. Furthermore, we show that KLRG1 binds N
      and R-cadherins. Finally, we demonstrate that E-cadherin binding of KLRG1
      prevents the lysis of E-cadherin-expressing targets by KLRG1+ NK cells. These
      results suggest that KLRG1 ligation by E-, N-, or R-cadherins may regulate the
      cytotoxicity of killer cells to prevent damage to tissues expressing the
      cadherins.

PMID- 16461341
TI  - H2-M3-restricted CD8+ T cells are not required for MHC class Ib-restricted
      immunity against Listeria monocytogenes.
AB  - Studies using major histocompatibility complex (MHC)-Ia-deficient mice have shown
      that MHC-Ib-restricted CD8+ T cells can clear infections caused by intracellular
      pathogens such as Listeria monocytogenes. M3-restricted CD8+ T cells, which
      recognize short hydrophobic N-formylated peptides, appear to comprise a
      substantial portion of the MHC-Ib-restricted T cell response in the mouse model
      of L. monocytogenes infection. In this study, we isolated formyltransferase (fmt)
      mutant strains of L. monocytogenes that lacked the ability to add formyl groups
      to nascent polypeptides. These fmt mutant Listeria strains did not produce
      antigens that could be recognized by M3-restricted T cells. We showed that
      immunization of MHC-Ia-deficient mice with fmt mutant Listeria resulted in
      stimulation of a protective memory response that cleared subsequent challenge
      with wild-type L. monocytogenes, despite the fact that M3-restricted CD8+ T cells
      did not proliferate in these mice. These data suggest that M3-restricted T cells
      are not required for protection against L. monocytogenes and underscore the
      importance of searching for new antigen-presenting molecules among the large MHC
      Ib family of proteins.

PMID- 16461343
TI  - Identification of substrates of human protein-tyrosine phosphatase PTPN22.
AB  - Stimulation of mature T cells activates a downstream signaling cascade involving
      temporally and spatially regulated phosphorylation and dephosphorylation events
      mediated by protein-tyrosine kinases and phosphatases, respectively. PTPN22
      (Lyp), a non-receptor protein-tyrosine phosphatase, is expressed exclusively in
      cells of hematopoietic origin, notably in T cells where it represses signaling
      through the T cell receptor. We used substrate trapping coupled with mass
      spectrometry-based peptide identification in an unbiased approach to identify
      physiological substrates of PTPN22. Several potential substrates were identified
      in lysates from pervanadate-stimulated Jurkat cells using PTPN22-D195A/C227S, an
      optimized substrate trap mutant of PTPN22. These included three novel PTPN22
      substrates (Vav, CD3epsilon, and valosin containing protein) and two known
      substrates of PEP, the mouse homolog of PTPN22 (Lck and Zap70). T cell antigen
      receptor (TCR) zeta was also identified as a potential substrate in Jurkat
      lysates by direct immunoblotting. In vitro experiments with purified recombinant
      proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated
      Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native
      PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr
      394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck)
      or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in
      cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when
      both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate
      of PTPN22.

PMID- 16461342
TI  - Cytolytic responses: cadherins put out the fire.
AB  - Cytotoxic lymphocytes, such as natural killer (NK) cells and CD8+ T cells,
      provide an essential defense against intracellular pathogens and tumors. During
      target cell recognition, these cells receive both activating and inhibitory
      signals. The cell must evaluate these opposing signals and determine the
      appropriate response: activation or inhibition. Classically, inhibitory signals
      are mediated by receptors that recognize MHC class I molecules (1). But recent
      studies, including one in this issue, suggest that MHC class I-independent
      inhibitory signals can also result in inhibition of cytotoxic cells.

PMID- 16461345
TI  - Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein: implications
      in the regulation of its hexamerization and exocytosis.
AB  - Pctaire1, a member of the cyclin-dependent kinase (Cdk)-related family, has
      recently been shown to be phosphorylated and regulated by Cdk5/p35. Although
      Pctaire1 is expressed in both neuronal and non-neuronal cells, its precise
      functions remain elusive. We performed a yeast two-hybrid screen to identify
      proteins that interact with Pctaire1. N-Ethylmaleimide-sensitive fusion protein
      (NSF), a crucial factor in vesicular transport and membrane fusion, was
      identified as one of the Pctaire1 interacting proteins. We demonstrate that the
      D2 domain of NSF, which is required for the oligomerization of NSF subunits,
      binds directly to and is phosphorylated by Pctaire1 on serine 569. Mutation of
      this phosphorylation site on NSF (S569A) augments its ability to oligomerize.
      Moreover, inhibition of Pctaire1 activity by transfecting its kinase-dead (KD)
      mutant into COS-7 cells enhances the self-association of NSF. Interestingly,
      Pctaire1 associates with NSF and synaptic vesicle-associated proteins in adult
      rat brain. To investigate whether Pctaire1 phosphorylation of NSF is involved in
      regulation of Ca(2+)-dependent exocytosis, we examined the effect of expressing
      Pctaire1 or NSF phosphorylation mutants on the regulated secretion of growth
      hormone from PC12 cells. Interestingly, expression of either Pctaire1-KD or NSF
      S569A in PC12 cells significantly increases high K(+)-stimulated growth hormone
      release. Taken together, our findings provide the first demonstration that
      Pctaire1 phosphorylation of NSF regulates the ability of NSF to oligomerize,
      implicating an unexpected role of this kinase in modulating exocytosis. These
      findings open a new avenue of research in studying the functional roles of
      Pctaire1 in the nervous system.

PMID- 16461344
TI  - Interaction of beta-1,3-glucan with its recognition protein activates hemolymph
      proteinase 14, an initiation enzyme of the prophenoloxidase activation system in
      Manduca sexta.
AB  - A serine proteinase pathway in insect hemolymph leads to prophenoloxidase
      activation, an innate immune response against pathogen infection. In the tobacco
      hornworm Manduca sexta, recombinant hemolymph proteinase 14 precursor (pro-HP14)
      interacts with peptidoglycan, autoactivates, and initiates the proteinase cascade
      (Ji, C., Wang, Y., Guo, X., Hartson, S., and Jiang, H. (2004) J. Biol. Chem. 279,
      34101-34106). Here, we report the purification and characterization of pro-HP14
      from the hemolymph of bacteria-injected M. sexta larvae. The zymogen, consisting
      of a single polypeptide with a molecular mass of 68.5 kDa, is truncated at the
      amino terminus. It is converted to a two-chain active form in the presence of
      beta-1,3-glucan (a fungal cell wall component) and beta-1,3-glucan recognition
      protein-2. The 45-kDa heavy chain contains four low-density lipoprotein receptor
      A repeats, one Sushi domain, and one unique cysteine-rich region, whereas the 30
      kDa light chain contains a serine proteinase domain, which was labeled by
      [(3)H]diisopropyl fluorophosphate. Pro-HP14 in the plasma strongly binds curdlan,
      zymosan, and yeast and interacts with peptidoglycan and Micrococcus luteus.
      Addition of autoactivated HP14 elevated phenoloxidase activity level in the
      larval plasma. Recombinant M. sexta serpin-1I reduced prophenoloxidase activation
      by inhibiting HP14. These data are consistent with the current model on
      initiation and regulation of the prophenoloxidase activation cascade upon
      recognition of pathogen-associated molecular patterns by specific pattern
      recognition proteins.

PMID- 16461346
TI  - Tumor necrosis factor-alpha increases circulating osteoclast precursor numbers by
      promoting their proliferation and differentiation in the bone marrow through up
      regulation of c-Fms expression.
AB  - Osteoclasts are essential cells for bone erosion in inflammatory arthritis and
      are derived from cells in the myeloid lineage. Recently, we reported that tumor
      necrosis factor-alpha (TNFalpha) increases the blood osteoclast precursor (OCP)
      numbers in arthritic patients and animals, which are reduced by anti-TNF therapy,
      implying that circulating OCPs may have an important role in the pathogenesis of
      erosive arthritis. The aim of this study is to investigate the mechanism by which
      TNFalpha induces this increase in OCP frequency. We found that TNFalpha
      stimulated cell division and conversion of CD11b+/Gr-1-/lo/c-Fms- to CD11b+/Gr-1
      /lo/c-Fms+ cells, which was not blocked by neutralizing macrophage colony
      stimulating factor (M-CSF) antibody. Ex vivo analysis of monocytes demonstrated
      the following: (i) blood CD11b+/Gr-1-/lo but not CD11b-/Gr-1- cells give rise to
      osteoclasts when they were cultured with receptor activator NF-kappaB ligand and
      M-CSF; and (ii) TNF-transgenic mice have a significant increase in blood
      CD11b+/Gr-1-/lo cells and bone marrow proliferating CD11b+/Gr-1-/lo cells.
      Administration of TNFalpha to wild type mice induced bone marrow CD11b+/Gr-1-/lo
      cell proliferation, which was associated with an increase in CD11b+/Gr-1-/lo OCPs
      in the circulation. Thus, TNFalpha directly stimulates bone marrow OCP genesis by
      enhancing c-Fms expression. This results in progenitor cell proliferation and
      differentiation in response to M-CSF, leading to an enlargement of the marrow OCP
      pool. Increased marrow OCPs subsequently egress to the circulation, forming a
      basis for elevated OCP frequency. Therefore, the first step of TNF-induced
      osteoclastogenesis is at the level of OCP genesis in the bone marrow, which
      represents another layer of regulation to control erosive disease.

PMID- 16461347
TI  - Positioned nucleosomes due to sequential remodeling of the yeast U6 small nuclear
      RNA chromatin are essential for its transcriptional activation.
AB  - Transcription from the yeast SNR6 (U6 small nuclear RNA) chromatin, a gene
      transcribed by the enzyme RNA polymerase III, depends on its transcription factor
      IIIC (TFIIIC) and the promoter elements (the intragenic box A and box B located
      downstream to its terminator) to which TFIIIC binds. The genes transcribed by
      polymerase III generally lack the upstream promoter elements where TFIIIC is
      known to recruit the transcription initiation factor TFIIIB. The TFIIIC-dependent
      chromatin remodeling of the gene in vitro that involves translational positioning
      of a nucleosome between boxes A and B is found to be essential for its
      transcriptional activation. We show here that the role of TFIIIC is not limited
      to the recruitment of TFIIIB on chromatin templates. The pre-binding of TFIIIB to
      the SNR6 TATA box in the upstream gene region does not alleviate TFIIIC
      requirement for transcriptional activation of the chromatin. Binding of TFIIIC to
      an array of pre-positioned nucleosomes results in an upward shift of the single
      nucleosome between boxes A and B. The approximately 40-bp shift of this
      nucleosome in the 3' to 5' direction leads to increased nuclease sensitivity of
      the approximately 40-bp DNA 3' to the upstream TATA box. Further chromatin
      remodeling accompanies the binding of TFIIIB in the next step. This two-step
      remodeling mechanism using the basal factors of the gene yields high
      transcription levels and generates a chromatin structure similar to that reported
      for the gene in vivo.

PMID- 16461348
TI  - Agonist-stimulated beta-adrenergic receptor internalization requires dynamic
      cytoskeletal actin turnover.
AB  - Stimulation of beta-adrenergic receptors (betaARs) leads to sequential
      recruitment of beta-arrestin, AP-2 adaptor protein, clathrin, and dynamin to the
      receptor complex, resulting in endocytosis. Whether a dynamic actin cytoskeleton
      is required for betaAR endocytosis is not known. In this study, we have used
      beta(1)- and beta(2) ARs, two ubiquitously expressed members of the betaAR
      family, to comprehensively evaluate the requirement of the actin cytoskeleton in
      receptor internalization. The integrity of the actin cytoskeleton was manipulated
      with the agent latrunculin B (LB) and mutants of cofilin to depolymerize actin
      filaments. Treatment of cells with LB resulted in dose-dependent depolymerization
      of the cortical actin cytoskeleton that was associated with significant
      attenuation in internalization of beta(2)ARs, beta(1)ARs, and mutants of
      beta(1)ARs that internalize via either clathrin- or caveolin-dependent pathways.
      Importantly, LB treatment did not inhibit beta-arrestin translocation or dynamin
      recruitment to the agonist-stimulated receptor. To unequivocally demonstrate the
      requirement of the actin cytoskeleton for beta(2)AR endocytosis, we used an actin
      binding protein cofilin that biochemically depolymerizes and severs actin
      filaments. Isoproterenol-mediated internalization of beta(2)AR was completely
      blocked in the presence of wild type cofilin, which could be rescued by a mutant
      of cofilin that mimics a constitutive phosphorylated state and leads to normal
      agonist-stimulated beta(2)AR endocytosis. Finally, treatment with jasplakinolide,
      an inhibitor of actin turnover, resulted in dose-dependent inhibition of
      beta(2)AR internalization, suggesting that turnover of actin filaments at the
      receptor complex is required for endocytosis. Taken together, these data
      demonstrate that intact and functional dynamic actin cytoskeleton is required for
      normal betaAR internalization.

PMID- 16461349
TI  - Tumor necrosis factor-like weak inducer of apoptosis inhibits skeletal myogenesis
      through sustained activation of nuclear factor-kappaB and degradation of MyoD
      protein.
AB  - In this study we have investigated the effect and the mechanisms by which tumor
      necrosis factor-like weak inducer of apoptosis (TWEAK) modulates myogenic
      differentiation. Treatment of C2C12 myoblasts with TWEAK inhibited their
      differentiation evident by a decrease in the expression of creatine kinase,
      myosin heavy chain-fast twitch, myogenin, and the formation of multinucleated
      myotubes. TWEAK also inhibited the differentiation of mouse primary myoblasts.
      Conversely, the proliferation of C2C12 myoblasts and the expression of a cell
      cycle regulator cyclin D1 were increased in response to TWEAK treatment.
      Inhibition of cellular proliferation using hydroxyurea only partially reversed
      the inhibitory effect of TWEAK on myogenic differentiation. Treatment of C2C12
      myoblasts with TWEAK resulted in the activation of nuclear factor-kappaB (NF
      kappaB), the (IkappaB) IkappaB kinase (IKK) complex, and the phosphorylation and
      degradation of IkappaBalpha protein. Inhibition of NF-kappaB activity by
      overexpression of a dominant negative mutant of IkappaBalpha (IkappaBalphaDeltaN)
      significantly increased the myogenic differentiation in TWEAK-treated C2C12
      cultures. Furthermore, overexpression of a dominant negative mutant of IKKbeta
      (IKKbetaK44A) but not IKKalpha (IKKalphaK44M) reversed the inhibitory effect of
      TWEAK on myogenesis. TWEAK inhibited the expression of myogenic regulatory
      factors MyoD and myogenin and also induced the degradation of MyoD protein.
      Finally, inhibition of NF-kappaB activation through overexpression of IKKbetaK44A
      prevented the degradation of MyoD protein. Overall, our data suggest that TWEAK
      inhibits myogenesis through the activation of NF-kappaB signaling pathway and
      degradation of MyoD protein.

PMID- 16461350
TI  - Visual arrestin binding to microtubules involves a distinct conformational
      change.
AB  - Recently we found that visual arrestin binds microtubules and that this
      interaction plays an important role in arrestin localization in photoreceptor
      cells. Here we use site-directed mutagenesis and spin labeling to explore the
      molecular mechanism of this novel regulatory interaction. The microtubule binding
      site maps to the concave sides of the two arrestin domains, overlapping with the
      rhodopsin binding site, which makes arrestin interactions with rhodopsin and
      microtubules mutually exclusive. Arrestin interaction with microtubules is
      enhanced by several "activating mutations" and involves multiple positive charges
      and hydrophobic elements. The comparable affinity of visual arrestin for
      microtubules and unpolymerized tubulin (K(D) > 40 mum and >65 mum, respectively)
      suggests that the arrestin binding site is largely localized on the individual
      alphabeta-dimer. The changes in the spin-spin interaction of a double-labeled
      arrestin indicate that the conformation of microtubule-bound arrestin differs
      from that of free arrestin in solution. In sharp contrast to rhodopsin, where
      tight binding requires an extended interdomain hinge, arrestin binding to
      microtubules is enhanced by deletions in this region, suggesting that in the
      process of microtubule binding the domains may move in the opposite direction.
      Thus, microtubule and rhodopsin binding induce different conformational changes
      in arrestin, suggesting that arrestin assumes three distinct conformations in the
      cell, likely with different functional properties.

PMID- 16461351
TI  - Effects of polycyclic aromatic hydrocarbons (PAHs) on vascular endothelial growth
      factor induction through phosphatidylinositol 3-kinase/AP-1-dependent, HIF-1alpha
      independent pathway.
AB  - Previous studies have demonstrated that exposure to polycyclic aromatic
      hydrocarbons (PAHs) and its derivatives is associated with an increased risk of
      skin cancers, and the carcinogenic effect of PAHs is thought to involve both
      tumor initiation and promotion. Whereas PAH tumor initiation is well
      characterized, the mechanisms involved in the tumor promotion of PAHs remain
      elusive. In the present study, we investigated the effects of PAHs on vascular
      endothelial growth factor (VEGF) expression by comparison of its induction
      between the active metabolite and its parent compound (B[a]PDE versus B[a]P) or
      between active compound and its relatively inactive analog (5-MCDE versus CDE).
      We found that exposure of cells to (+/-)-anti-benzo-[a]pyrene-7,8-diol-9,10
      epoxide (B[a]PDE) or (+/-)-anti-5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE)
      led to marked induction of VEGF in Cl41 cells, whereas benzo[a]pyrene (B[a]P) or
      chrysene-1,2-diol-3,4-epoxide (CDE) did not exhibit significant inductive
      effects. Exposure of cells to B[a]PDE and 5-MCDE did not induce HIF-1alpha
      activation, whereas AP-1 was significantly activated. Moreover, overexpression of
      TAM67 (a dominant-negative mutant c-Jun) dramatically blocked that VEGF
      induction. Electrophoretic mobility shift assay showed that AP-1 was only able to
      specifically recognize and bind to its AP-1 potential binding site within -1136
      and -1115 of the VEGF promoter region. Site-directed mutation of this AP-1
      binding site eliminated the VEGF transcriptional activity induced by B[a]PDE,
      suggesting that the AP-1 binding site between -1136 and -1115 in the VEGF
      promoter region is critical for VEGF induction by B[a]PDE. In addition,
      overexpression of Deltap85 (a dominant-negative mutant PI-3K) impaired B[a]PDE-
      and 5-MCDE-induced VEGF induction. Considering our previous findings that PI-3K
      is an upstream mediator for c-Jun/AP-1 activation, we conclude that the VEGF
      induction by B[a]PDE and 5-MCDE is through PI-3K/AP-1-dependent and HIF-1alpha
      independent pathways. These findings may help us to understand the mechanisms
      involved in PAH carcinogenic effects.

PMID- 16461352
TI  - PARP-2 interacts with TTF-1 and regulates expression of surfactant protein-B.
AB  - Thyroid transcription factor 1 (TTF-1/Nkx-2.1) plays a critical role in lung
      morphogenesis and regulates the expression of lung-specific genes, including the
      surfactant proteins required for pulmonary function after birth. The activity of
      TTF-1 is influenced by its interactions with other transcription factors and
      coactivators, including CBP/p300 and SRC-1. In this study, we have identified
      poly(ADP-ribose) polymerases (PARP-2 and PARP-1) as TTF-1 interacting proteins
      that influence its transcriptional activity. Endogenous PARP-2 was
      coimmunoprecipitated from transformed mouse lung epithelial cell (MLE15) extracts
      with TTF-1 and was identified by mass spectrometry. PARP-1 and Ku70/Ku80 were
      also coimmunoprecipitated from the cell extracts with TTF-1. The E domain of PARP
      2 interacted via the C-terminal domain of TTF-1. Both PARP-1 and PARP-2 enhanced
      the activity of the promoter of surfactant protein-B (Sftpb gene) but not other
      surfactant proteins in vitro. PARP-2 was selectively expressed in epithelial
      cells of the conducting and peripheral lung tubules of the fetal mouse lung from
      embryonic day 12.5 and was detected in bronchial epithelial cells in the adult
      lung at cellular sites consistent with that of surfactant protein B. PARP-2 and
      PARP-1 interact with TTF-1 and regulate the expression of surfactant protein B, a
      protein required for lung function.

PMID- 16461353
TI  - Regulation of the transient receptor potential channel TRPM2 by the Ca2+ sensor
      calmodulin.
AB  - TRPM2, a member of the transient receptor potential (TRP) superfamily, is a
      Ca(2+)-permeable channel activated by oxidative stress or tumor necrosis
      factoralpha involved in susceptibility to cell death. TRPM2 activation is
      dependent on the level of intracellular Ca(2+). We explored whether calmodulin
      (CaM) is the Ca(2+) sensor for TRPM2. HEK 293T cells were transfected with TRPM2
      and wild type CaM or mutant CaM (CaM(MUT)) with substitutions of all four EF
      hands. Treatment of cells expressing TRPM2 with H(2)O(2) or tumor necrosis factor
      alpha resulted in a significant increase in intracellular calcium ([Ca(2+)](i)).
      This was not affected by coexpression of CaM, suggesting that endogenous CaM
      levels are sufficient for maximal response. Cotransfection of CaM(MUT) with TRPM2
      dramatically inhibited the increase in [Ca(2+)](i), demonstrating the requirement
      for CaM in TRPM2 activation. Immunoprecipitation confirmed direct interaction of
      CaM and CaM(MUT) with TRPM2, and the Ca(2+) dependence of this association. CaM
      bound strongly to the TRPM2 N terminus (amino acids 1-730), but weakly to the C
      terminus (amino acids 1060-1503). CaM binding to an IQ-like motif (amino acids
      406-416) in the TRPM2 N terminus was demonstrated utilizing gel shift,
      immunoprecipitation, biotinylated CaM overlay, and pull-down assays. A
      substitution mutant of the IQ-like motif of TRPM2 (TRPM2-IQ(MUT1)) reduced but
      did not eliminate CaM binding to TRPM2, suggesting the presence of at least one
      other CaM binding site. The functional importance of the TRPM2 IQ-like motif was
      demonstrated by treatment of TRPM2-IQ(MUT1)-expressing cells with H(2)O(2). The
      increase in [Ca(2+)](i) observed with wild type TRPM2 was absent and cell
      viability was preserved. These data demonstrate the requirement for CaM in TRPM2
      activation. They suggest that Ca(2+) entering through TRPM2 enhances interaction
      of CaM with TRPM2 at the IQ-like motif in the N terminus, providing crucial
      positive feedback for channel activation.

PMID- 16461354
TI  - Intrinsic inhibition of the Hsp90 ATPase activity.
AB  - The molecular chaperone Hsp90 is required for the folding and activation of a
      large number of substrate proteins. These are involved in essential cellular
      processes ranging from signal transduction to viral replication. For the
      activation of its substrates, Hsp90 binds and hydrolyzes ATP, which is the key
      driving force for conformational conversions within the dimeric chaperone.
      Dimerization of Hsp90 is mediated by a C-terminal dimerization site. In addition,
      there is a transient ATP-induced dimerization of the two N-terminal ATP-binding
      domains. The resulting ring-like structure is thought to be the ATPase-active
      conformation. Hsp90 is a slow ATPase with a turnover number of 1 ATP/min for the
      yeast protein. A key question for understanding the molecular mechanism of Hsp90
      is how ATP hydrolysis is regulated and linked to conformational changes. In this
      study, we analyzed the activation process structurally and biochemically with a
      view to identify the conformational limitations of the ATPase reaction cycle. We
      showed that the first 24 amino acids stabilize the N-terminal domain in a rigid
      state. Their removal confers flexibility specifically to the region between amino
      acids 98 and 120. Most surprisingly, the deletion of this structure results in
      the complete loss of ATPase activity and in increased N-terminal dimerization.
      Complementation assays using heterodimeric Hsp90 show that this rigid lid acts as
      an intrinsic kinetic inhibitor of the Hsp90 ATPase cycle preventing N-terminal
      dimerization in the ground state. On the other hand, this structure acts, in
      concert with the 24 N-terminal amino acids of the other N-terminal domain, to
      form an activated ATPase and thus regulates the turnover number of Hsp90.

PMID- 16461355
TI  - Anandamide uptake is consistent with rate-limited diffusion and is regulated by
      the degree of its hydrolysis by fatty acid amide hydrolase.
AB  - The uptake of arachidonoyl ethanolamide (anandamide, AEA) in rat basophilic
      leukemia cells (RBL-2H3) has been proposed to occur via a saturable transporter
      that is blocked by specific inhibitors. Measuring uptake at 25 s, when fatty acid
      amide hydrolase (FAAH) does not appreciably affect uptake, AEA accumulated via a
      nonsaturable mechanism at 37 degrees C. Interestingly, saturation was observed
      when uptake was plotted using unbound AEA at 37 degrees C. Such apparent
      saturation can be explained by rate-limited delivery of AEA through an unstirred
      water layer surrounding the cells (1). In support of this, we observed kinetics
      consistent with rate-limited diffusion at 0 degrees C. Novel transport inhibitors
      have been synthesized that are either weak FAAH inhibitors or do not inhibit FAAH
      in vitro (e.g. UCM707, OMDM2, and AM1172). In the current study, none of these
      purported AEA transporter inhibitors affected uptake at 25 s. Longer incubation
      times illuminate downstream events that drive AEA uptake. Unlike the situation at
      25 s, the efficacy of these inhibitors was unmasked at 5 min with appreciable
      inhibition of AEA accumulation correlating with partial inhibition of AEA
      hydrolysis. The uptake and hydrolysis profiles observed with UCM707, VDM11,
      OMDM2, and AM1172 mirrored two selective and potent FAAH inhibitors CAY10400 and
      URB597 (at low concentrations), indicating that weak inhibition of FAAH can have
      a pronounced effect upon AEA uptake. At 5 min, the putative transport inhibitors
      did not reduce AEA uptake in FAAH chemical knock-out cells. This strongly
      suggests that the target of UCM707, VDM11, OMDM2, and AM1172 is not a transporter
      at the plasma membrane but rather FAAH, or an uncharacterized intracellular
      component that delivers AEA to FAAH. This system is therefore unique among
      neuro/immune modulators because AEA, an uncharged hydrophobic molecule, diffuses
      into cells and partial inhibition of FAAH has a pronounced effect upon its
      uptake.

PMID- 16461356
TI  - Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain
      of adhesion and degranulation-promoting adaptor protein.
AB  - The immune cell adaptor adhesion and degranulation promoting adaptor protein
      (ADAP) and its binding to T-cell adaptor Src kinase-associated protein of 55 kDa
      (SKAP-55) play a key role in the modulation of T-cell adhesion. While primary
      binding occurs via SKAP-55 SH3 domain binding to a proline-rich region in ADAP, a
      second interaction occurs between the ADAP C-terminal SH3 domain (ADAP-SH3c) and
      a non-canonical RKXXY294XXY297 motif in SKAP-55. Increasing numbers of non
      canonical SH3 domain binding motifs have been identified in a number of
      biological systems. The presence of tyrosine residues in the SKAP-55
      RKXXY294XXY297 motif suggested that phosphorylation might influence this unusual
      SH3 domain interaction. Here, we show that the Src kinase p59fyn can induce the
      in vivo phosphorylation of the motif, and this event blocks ADAP-SH3c domain
      binding to the peptide motif. The importance of tyrosine phosphorylation was
      confirmed by plasmon resonance interaction analysis showing that phosphorylation
      of Tyr294 residue plays a central role in mediating dissociation, whereas
      phosphorylation of the second Tyr297 had no effect. Although loss of this
      secondary interaction did not result in the disruption of the complex, the Y294F
      mutation blocked T-cell receptor-induced up-regulation of lymphocyte function
      associated antigen-1-mediated adhesion to intercellular adhesion molecule-1 and
      interleukin-2 promoter activity. Our findings identify a RKXXY294 motif in SKAP
      55 that mediates unique ADAP SH3c domain binding and is needed for LFA-1-mediated
      adhesion and cytokine production.

PMID- 16461357
TI  - Beta1,4-galactosyltransferase V functions as a positive growth regulator in
      glioma.
AB  - beta1,4-galactosyltransferase V (GalT V; EC 2.4.1.38) can effectively
      galactosylate the GlcNAcbeta1-->6Man arm of the highly branched N-glycans that
      are characteristic of glioma. Previously, we have reported that the expression of
      GalT V is increased in the process of glioma. However, currently little is known
      about the role of GalT V in this process. In this study, the ectopic expression
      of GalT V could promote the invasion and survival of glioma cells and transformed
      astrocytes. Furthermore, decreasing the expression of GalT V in glioma cells
      promoted apoptosis, inhibited the invasion and migration and the ability of tumor
      formation in vivo, and reduced the activation of AKT. In addition, the activity
      of GalT V promoter could be induced by epidermal growth factor, dominant active
      Ras, ERK1, JNK1, and constitutively active AKT. Taken together, our results
      suggest that GalT V functioned as a novel glioma growth activator and might
      represent a novel target in glioma therapy.

PMID- 16461358
TI  - Nuclear gene variation and molecular dating of the cichlid species flock of Lake
      Malawi.
AB  - The cichlid fishes of Lake Malawi are famously diverse. However, evolutionary
      studies have been difficult because of their recent and uncertain phylogenetic
      history. Portions of 12 nuclear loci were sequenced in nine rock-dwelling species
      (mbuna) and three representatives of pelagic nonmbuna species. In contrast to the
      pattern of variation at mitochondrial genes, which do provide phylogenetic
      resolution at the level of mbuna versus nonmbuna, and among some genera, the
      nuclear loci were virtually devoid of phylogenetic signal. Only a small minority
      of variable positions were phylogenetically informative, and no phylogenetic
      branches are supported by more than one site. From the nuclear gene perspective
      the Malawian radiation appears to be a star phylogeny, as if the founding of the
      lake was accompanied by a partial bottleneck. The pattern is different from that
      found in Lake Victoria, in which nuclear loci share large amounts of ancestral
      variation. In the case of nuclear genes of Lake Malawi, the absence of
      phylogenetically informative variation suggests a relative absence of ancestral
      variation. Nuclear genes also differed from the mitochondria in having nearly
      twice the amount of divergence from Oreochromis (tilapia). An approximate
      splitting time between mbuna and nonmbuna lineages was estimated as 0.7 Myr.
      Oreochromis is estimated to have diverged from the cichlids in Lake Malawi and
      Lake Tanganyika about 18 MYA.

PMID- 16461359
TI  - A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear
      body formation and degradation of expanded polyglutamine protein.
AB  - Polyglutamine diseases are inherited neurodegenerative diseases caused by the
      expanded polyglutamine proteins (polyQs). We have identified a novel guanosine
      triphosphatase (GTPase) named CRAG that contains a nuclear localization signal
      (NLS) sequence and forms nuclear inclusions in response to stress. After
      ultraviolet irradiation, CRAG interacted with and induced an enlarged ring-like
      structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent
      manner. Reactive oxygen species (ROS) generated by polyQ accumulation triggered
      the association of CRAG with polyQ and the nuclear translocation of the CRAG
      polyQ complex. Furthermore, CRAG promoted the degradation of polyQ at PML/CRAG
      bodies through the ubiquitin-proteasome pathway. CRAG knockdown by small
      interfering RNA in neuronal cells consistently blocked the nuclear translocation
      of polyQ and enhanced polyQ-mediated cell death. We propose that CRAG is a
      modulator of PML function and dynamics in ROS signaling and is protectively
      involved in the pathogenesis of polyglutamine diseases.

PMID- 16461360
TI  - pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein response
      activator pXBP1(S) in mammalian ER stress response.
AB  - Upon the accumulation of unfolded proteins in the mammalian endoplasmic reticulum
      (ER), X-box binding protein 1 (XBP1) premessenger RNA (premRNA) is converted to
      mature mRNA by unconventional splicing that is mediated by the endonuclease
      inositol-requiring enzyme 1. The transcription factor protein (p) XBP1 spliced
      (S), which is translated from mature XBP1 mRNA, contains the nuclear localization
      signal and the transcriptional activation domain and activates the transcription
      of target genes, including those encoding ER chaperones in the nucleus. We show
      that pXBP1 unspliced (U) encoded in XBP1 pre-mRNA was constitutively expressed
      and markedly accumulated at the recovery phase of ER stress. pXBP1(U) contained
      the nuclear exclusion signal instead of the transcriptional activation domain and
      shuttled between the nucleus and the cytoplasm. Interestingly, pXBP1(U) formed a
      complex with pXBP1(S), and the pXBP1(U)-pXBP1(S) complex was sequestered from the
      nucleus. Moreover, the complex was rapidly degraded by proteasomes because of the
      degradation motif contained in pXBP1(U). Thus, pXBP1(U) is a negative feedback
      regulator of pXBP1(S), which shuts off the transcription of target genes during
      the recovery phase of ER stress.

PMID- 16461361
TI  - Transcriptional repression induces a slowly progressive atypical neuronal death
      associated with changes of YAP isoforms and p73.
AB  - Transcriptional disturbance is implicated in the pathology of polyglutamine
      diseases, including Huntington's disease (HD). However, it is unknown whether
      transcriptional repression leads to neuronal death or what forms that death might
      take. We found transcriptional repression-induced atypical death (TRIAD) of
      neurons to be distinct from apoptosis, necrosis, or autophagy. The progression of
      TRIAD was extremely slow in comparison with other types of cell death. Gene
      expression profiling revealed the reduction of full-length yes-associated protein
      (YAP), a p73 cofactor to promote apoptosis, as specific to TRIAD. Furthermore,
      novel neuron-specific YAP isoforms (YAPDeltaCs) were sustained during TRIAD to
      suppress neuronal death in a dominant-negative fashion. YAPDeltaCs and activated
      p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin
      (htt) transgenic mice. YAPDeltaCs also markedly attenuated Htt-induced neuronal
      death in primary neuron and Drosophila melanogaster models. Collectively,
      transcriptional repression induces a novel prototype of neuronal death associated
      with the changes of YAP isoforms and p73, which might be relevant to the HD
      pathology.

PMID- 16461362
TI  - NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome
      is necessary for centriole duplication and spindle assembly.
AB  - The centrosome is the major microtubule organizing structure in somatic cells.
      Centrosomal microtubule nucleation depends on the protein gamma-tubulin. In
      mammals, gamma-tubulin associates with additional proteins into a large complex,
      the gamma-tubulin ring complex (gammaTuRC). We characterize NEDD1, a centrosomal
      protein that associates with gammaTuRCs. We show that the majority of gammaTuRCs
      assemble even after NEDD1 depletion but require NEDD1 for centrosomal targeting.
      In contrast, NEDD1 can target to the centrosome in the absence of gamma-tubulin.
      NEDD1-depleted cells show defects in centrosomal microtubule nucleation and form
      aberrant mitotic spindles with poorly separated poles. Similar spindle defects
      are obtained by overexpression of a fusion protein of GFP tagged to the carboxy
      terminal half of NEDD1, which mediates binding to gammaTuRCs. Further, we show
      that depletion of NEDD1 inhibits centriole duplication, as does depletion of
      gamma-tubulin. Our data suggest that centriole duplication requires NEDD1
      dependent recruitment of gamma-tubulin to the centrosome.

PMID- 16461363
TI  - Atrial and ventricular myosin heavy-chain expression in the developing chicken
      heart: strengths and limitations of non-radioactive in situ hybridization.
AB  - Myosin heavy-chain (MHC) isoforms are major structural components of the
      contractile apparatus of the heart muscle. Their spatio-temporal patterns of
      expression have been used as a tool to dissect cardiac development and
      differentiation. Although extensively investigated, controversy still exists
      concerning the expression patterns of atrial (AMHC), ventricular (VMHC), and
      cardiac myosin heavy-chain (CMHC) during development in the heart. In this study,
      we describe that probe length, probe concentration, and staining time in the non
      radioactive in situ hybridization procedure seriously influence the observed
      pattern of MHC expression and the subsequent interpretation, explaining the
      divergent opinions in the field. Using a variety of external and internal
      controls for the in situ hybridization procedure, we demonstrate that both AMHC
      and VMHC are expressed throughout the entire heart tube during early development.
      During subsequent development, VMHC becomes restricted to the ventricles, whereas
      AMHC remains expressed in the atria, and, at substantially lower levels, is
      detected in the ventricles. These results are discussed in the context of
      methodological constraints of demonstrating patterns of gene expression. This
      manuscript contains online supplemental material at http://www.jhc.org. Please
      visit this article online to view these materials.

PMID- 16461365
TI  - Immunocytochemical study of amelogenin deposition during the early odontogenesis
      of molars in alendronate-treated newborn rats.
AB  - Newborn rats were treated with sodium alendronate to study how enamel is formed
      and the effect of alendronate during early odontogenesis. Ultrastructural
      analysis combined with high-resolution immunocytochemistry for amelogenin was
      carried out. Twelve rats were subjected to daily SC injections of sodium
      alendronate (2.5 mg/kg/day) for 3 days on their dorsal region, whereas three rats
      were daily injected with saline solution as a control. Molar tooth germs from 3
      day-old rats were fixed under microwave irradiation in 0.1% glutaraldehyde + 4%
      formaldehyde buffered at pH 7.2 with 0.1 M sodium cacodylate. The specimens were
      left undecalcified, postfixed with osmium tetroxide, dehydrated, and embedded in
      LR White resin. Ultrathin sections were incubated with a chicken anti-24-kDa rat
      amelogenin antibody, a secondary antibody, and finally with a protein A-gold
      complex. Large patches of amelogenin were present over the unmineralized mantle
      dentin and at early secretory ameloblasts. At more advanced stages, they were
      also detected at the enamel matrix, as well as in the mineralized dentin, at the
      periodontoblastic space of the dentinal tubules, and at the predentin. It is
      likely that the main effect of alendronate at early stages of odontogenesis is
      the increase of synthesis/secretion of amelogenin, promoting its deposition
      within the forming dentin and enamel.

PMID- 16461364
TI  - Tissue expression of the novel serine carboxypeptidase Scpep1.
AB  - We previously identified a novel gene designated retinoid-inducible serine
      carboxypeptidase (RISC or Scpep1). Here we characterize a polyclonal antibody
      raised to Scpep1 and assess its localization in mouse cells and tissues. Western
      blot analysis revealed an immunospecific approximately 35-kDa protein
      corresponding to endogenous Scpep1. This protein is smaller than the predicted
      approximately 51-kDa, suggesting that Scpep1 is proteolytically cleaved to a
      mature enzyme. Immunohistochemical studies demonstrate Scpep1 expression in
      embryonic heart and vasculature as well as in adult aortic smooth muscle cells
      and endothelial cells. Scpep1 displays a broad expression pattern in adult
      tissues with detectable levels in epithelia of digestive tract and urinary
      bladder, islet of Langerhans, type II alveolar cells and macrophages of lung,
      macrophage-like cells of lymph nodes and spleen, Leydig cells of testis, and
      nerve fibers in brain and ganglia. Consistent with previous mRNA studies in
      kidney, Scpep1 protein is restricted to proximal convoluted tubular epithelium
      (PCT). Immunoelectron microscopy shows enriched Scpep1 within lysosomes of the
      PCT, and immunofluorescence microscopy colocalizes Scpep1 with lysosomal
      associated membrane protein-2. These results suggest that Scpep1 is a widely
      distributed lysosomal protease requiring proteolytic cleavage for activity. The
      highly specific Scpep1 antibody characterized herein provides a necessary reagent
      for elucidating Scpep1 function.

PMID- 16461366
TI  - Active remodeling in idiopathic interstitial pneumonias: evaluation of collagen
      types XII and XIV.
AB  - Fibril-associated collagens with interrupted triple helices (FACITs) XII and XIV
      act as fibril organizers and assist in the maintenance of uniform fibril size. We
      investigated the spatial expression patterns of collagens XII and XIV in
      cryptogenic organizing pneumonia (COP)/organizing pneumonia (OP) and in
      idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) and
      compared them to normal human lung. Study subjects included 10 patients with
      COP/OP, 10 patients with IPF/UIP, and 8 control subjects. Immunostaining for
      collagens XII and XIV was carried out in paraffin-embedded human lung tissue
      sections. Picrosirius red histochemical staining for collagen I expression and
      electron microcopy to evaluate fibril diameter were also performed. In normal
      lung, collagens XII and XIV were expressed in perivascular and subpleural
      connective tissue. In COP/OP, both collagens showed intense staining in
      perivascular connective tissue, thickened alveolar septae, and subpleural areas.
      In IPF/UIP, XII and XIV were expressed in perivascular connective tissue, in
      areas of established fibrosis, and in areas of subpleural thickening. Only
      collagen XII was expressed in granulation tissue plugs in COP/OP and in
      fibroblastic foci in IPF/UIP. Collagen type I was overexpressed in fibrotic
      areas. Electron micrographs revealed obvious fibril diameter alteration and
      fusion in the same areas. FACITs XII and XIV are expressed in normal and fibrotic
      lung. Unlike collagen XIV, collagen XII was expressed in granulation tissue plugs
      in COP/OP and in fibroblast foci in IPF/UIP. This may suggest a possible distinct
      role for both collagens in the modulation of the extracellular matrix during the
      onset of fibrotic process.

PMID- 16461367
TI  - Specific immunolabeling of brain macrophages and microglial cells in the
      developing and mature chick central nervous system.
AB  - The present study showed that the HIS-C7 monoclonal antibody, which recognizes
      the chick form of CD45, is a specific marker for macrophages/microglial cells in
      the developing and mature chick central nervous system (CNS). HIS-C7-positive
      cells were characterized according to their morphological features and
      chronotopographical distribution patterns within developing and adult CNS,
      similar to those of macrophages/microglial cells in the quail CNS and confirmed
      by their histochemical labeling with Ricinus communis agglutinin I, a lectin that
      recognizes chick microglial cells. Therefore, the HIS-C7 antibody is a valuable
      tool to identify brain macrophage and microglial cells in studies of the
      function, development, and pathology of the chick brain. CD45 expression differed
      between chick microglia (as revealed with HIS-C7 antibody) and mouse microglial
      cells (as revealed with an antibody against mouse form of CD45). Thus, a
      discontinuous label was seen on mouse microglial cells with the anti-mouse CD45
      immunostaining, whereas the entire surface of chick microglial cells was labeled
      with the anti-chick CD45 staining. The functional relevance of these differences
      between species has yet to be determined.

PMID- 16461368
TI  - Mechanistic basis of differences in Ca2+ -handling properties of sarcoplasmic
      reticulum in right and left ventricles of normal rat myocardium.
AB  - This study investigated Ca2+ -cycling properties of sarcoplasmic reticulum (SR)
      in right ventricle (RV) and left ventricle (LV) of normal rat myocardium.
      Intracellular Ca2+ transients and contractile function were monitored in freshly
      isolated myocytes from RV and LV. SR in RV displayed nearly fourfold lower rates
      of ATP-energized Ca2+ uptake in vitro than SR of LV. The Ca2+ concentration
      required for half-maximal activation of Ca2+ transport was nearly twofold higher
      in SR of RV. The lower Ca2+ -sequestering activity of SR in RV was accompanied by
      a matching decrement in Ca2+ -induced phosphoenzyme formation during the
      catalytic cycle of the Ca2+ -pumping ATPase (SERCA2). Western immunoblot analysis
      showed that protein levels of Ca2+ -ATPase and its inhibitor phospholamban (PLN)
      were only approximately 15% lower in SR of RV than in SR of LV.
      Coimmunoprecipitation experiments revealed that PLN-bound, functionally inert
      Ca2+ -ATPase molecules in SR of RV greatly exceed (> 50%) that in SR of LV.
      Endogenous Ca2+/calmodulin-dependent protein kinase-mediated phosphorylation of
      SR substrates did not abolish the huge disparity in SR Ca2+ pump function between
      RV and LV. Intracellular Ca2+ transients, evoked by electrical field stimulation,
      were significantly prolonged in RV myocytes compared with LV myocytes, mainly
      because of slow decay of intracellular Ca2+ concentration. The slow decay of
      intracellular Ca2+ concentration in RV and consequent decrease in the speed of RV
      relaxation may promote temporal synchrony of the end of diastole in RV and LV.
      The preponderance of functionally silent SR Ca2+ pumps in RV reflects a higher
      diastolic reserve required to protect and maintain RV function in the face of a
      sudden rise in afterload or resistance in the pulmonary circulation.

PMID- 16461369
TI  - Significance of changes in TNF-alpha and IL-10 levels in the progression of heart
      failure subsequent to myocardial infarction.
AB  - We tested whether a decrease in the ratio of interleukin-10 (IL-10) to tumor
      necrosis factor-alpha (TNF-alpha) correlates with the decrease in cardiac
      function in heart failure. It has been suggested that TNF-alpha plays a role in
      the progression of heart failure, and the effect of TNF-alpha in many tissues is
      modulated by IL-10. Any relation of these two cytokines to heart failure has
      never been examined. Cardiac function was assessed by echocardiographic and
      hemodynamic techniques in coronary artery-ligated rats at 1, 4, 8, and 16 wk
      after myocardial infarction (MI). Membrane-bound and soluble fractions of TNF
      alpha and IL-10 proteins, the ratio of TNF-alpha to IL-10, and TNF-alpha and IL
      10 mRNA levels were analyzed. Losartan was used to modify cardiac function in
      rats 4 wk after MI to further validate the relation between the IL-10-to-TNF
      alpha ratio and cardiac function. Cardiac function deteriorated with time in all
      coronary artery-ligated groups, with severe failure at 16 wk after MI. Membrane
      bound and soluble TNF-alpha protein fractions were increased 1 and 4 wk after MI,
      whereas TNF-alpha mRNA was increased 4 and 8 wk after MI. Membrane-bound IL-10
      protein and mRNA levels were decreased 4, 8, and 16 wk after MI. The decrease in
      the IL-10-to-TNF-alpha protein ratio in all coronary artery-ligated groups
      correlated with the depressed cardiac function. Losartan improved cardiac
      function, membrane-bound and soluble TNF-alpha and IL-10 protein levels, the
      ratio of IL-10 to TNF-alpha, and IL-10 mRNA. This study suggests that a decrease
      in IL-10 and IL-10-to-TNF-alpha ratio correlates with depressed cardiac function.

PMID- 16461370
TI  - Efficacy and mechanism of adenovirus-mediated VEGF-165 gene therapy for
      augmentation of skin flap viability.
AB  - Skin ischemic necrosis due to vasospasm and/or insufficient vascularity is the
      most common complication in the distal portion of the skin flap in reconstructive
      surgery. This project was designed to test our hypothesis that preoperative
      subdermal injection of adenoviral vectors encoding genes for vascular endothelial
      growth factor-165 (Ad.VEGF-165) or endothelial nitric oxide (NO) synthase
      (Ad.eNOS) effectively augments skin viability in skin flap surgery and that the
      mechanism of Ad.VEGF-165 gene therapy involves an increase in synthesis/release
      of the angiogenic and vasodilator factor NO. PBS (0.5 ml) or PBS containing
      Ad.VEGF-165, Ad.eNOS, or adenovirus (Ad.Null) was injected subdermally into the
      distal half of a mapped rat dorsal skin flap (4 x 10 cm) 7 days preoperatively,
      and skin flap viability was assessed 7 days postoperatively. Local subdermal gene
      therapy with 2 x 10(7)-2 x 10(10) plaque-forming units of VEGF-165 increased skin
      flap viability compared with PBS- or Ad.Null-injected control (P < 0.05).
      Subdermal Ad.VEGF-165 and Ad.eNOS gene therapies were equally effective in
      increasing skin flap viability at 5 x 10(8) plaque-forming units. Subdermal
      Ad.VEGF-165 therapy was associated with upregulation of eNOS protein expression,
      Ca2+ -dependent NOS activity, synthesis/release of NO, and increase in capillary
      density and blood flow in the distal portion of the skin flap. Injection of the
      NOS inhibitor Nomega-nitro-L-arginine (15 mg/kg im), but not the cyclooxygenase
      inhibitor indomethacin (5 mg/kg im), 45 min preoperatively completely abolished
      the increase in skin flap blood flow and viability induced by Ad.VEGF-165
      injected subdermally into the mapped skin flap 7 days preoperatively. We have
      demonstrated for the first time that 1) Ad.VEGF-165 and Ad.eNOS mapped skin flap
      injected subdermally into the mapped skin flap 7 days preoperatively are equally
      effective in augmenting viability in the rat dorsal skin flap compared with
      control, 2) the mechanism of subdermal Ad.VEGF-165 gene therapy in augmenting
      skin flap viability involves an increase in NO synthesis/release downstream of
      upregulation of eNOS protein expression and Ca2+ -dependent NOS activity, and 3)
      the vasodilating effect of NO may predominantly mediate subdermal Ad.VEGF gene
      therapy in augmenting skin flap blood flow and viability.

PMID- 16461371
TI  - Is oxygen supply a limiting factor for survival during rewarming from profound
      hypothermia?
AB  - It has been postulated that unsuccessful resuscitation of victims of accidental
      hypothermia is caused by insufficient tissue oxygenation. The aim of this study
      was to test whether inadequate O2 supply and/or malfunctioning O2 extraction
      occur during rewarming from deep/profound hypothermia of different duration.
      Three groups of rats (n = 7 each) were used: group 1 served as normothermic
      control for 5 h; groups 2 and 3 were core cooled to 15 degrees C, kept at 15
      degrees C for 1 and 5 h, respectively, and then rewarmed. In both hypothermic
      groups, cardiac output (CO) decreased spontaneously by > 50% in response to
      cooling. O2 consumption fell to less than one-third during cooling but recovered
      completely in both groups during rewarming. During hypothermia, circulating blood
      volume in both groups was reduced to approximately one-third of baseline,
      indicating that some vascular beds were critically perfused during hypothermia.
      CO recovered completely in animals rewarmed after 1 h (group 2) but recovered to
      only 60% in those rewarmed after 5 h (group 3), whereas blood volume increased to
      approximately three-fourths of baseline in both groups. Metabolic acidosis was
      observed only after 5 h of hypothermia (15 degrees C). A significant increase in
      myocardial tissue heat shock protein 70 after rewarming in group 3, but not in
      group 2, indicates an association with the duration of hypothermia. Thus
      mechanisms facilitating O2 extraction function well during deep/profound
      hypothermia, and, despite low CO, O2 supply was not a limiting factor for
      survival in the present experiments.

PMID- 16461372
TI  - Angiotensin II infusion restores stimulated angiogenesis in the skeletal muscle
      of rats on a high-salt diet.
AB  - Elevated dietary salt intake has previously been demonstrated to have dramatic
      effects on microvascular structure and function. The purpose of this study was to
      determine whether a high-salt diet modulates physiological angiogenesis in
      skeletal muscle. Male Sprague-Dawley rats were placed on a control diet (0.4%
      NaCl by weight) or a high-salt diet (4.0% NaCl) before implantation of a chronic
      electrical stimulator. After seven consecutive days of unilateral hindlimb muscle
      stimulation, animals on control diets demonstrated a significant increase in
      microvessel density in the tibialis anterior muscle of the stimulated hindlimb
      relative to the contralateral control leg. High salt-fed rats demonstrated a
      complete inhibition of this angiogenic response, as well as a significant
      reduction in plasma ANG II levels compared with those of control animals. To
      investigate the role of ANG II suppression on the inhibitory effect of high-salt
      diets, a group of rats that were fed high salt were chronically infused with ANG
      II at a low dose. Maintenance of ANG II levels restored stimulated angiogenesis
      to control levels in animals fed a high-salt diet. Western blot analysis
      indicated that inhibition of angiogenesis in high salt-fed rats was not due to
      changes in VEGF or VEGF receptor type 1 protein expression in response to
      stimulation; however, the degree to which VEGF receptor 2 protein increased with
      stimulation was significantly lower in high salt-fed animals. This study
      demonstrates an inhibitory effect of high salt intake on stimulated angiogenesis
      and suggests a critical role for ANG II suppression in mediating this
      antiangiogenic effect.

PMID- 16461373
TI  - Deletion of peroxisome proliferator-activated receptor-alpha induces an
      alteration of cardiac functions.
AB  - The peroxisome proliferator-activated receptor-alpha (PPARalpha) plays a major
      role in the control of cardiac energy metabolism. The role of PPARalpha on
      cardiac functions was evaluated by using PPARalpha knockout (PPARalpha -/-) mice.
      Hemodynamic parameters by sphygmomanometric measurements show that deletion of
      PPARalpha did not affect systolic blood pressure and heart rate.
      Echocardiographic measurements demonstrated reduced systolic performance as shown
      by the decrease of left ventricular fractional shortening in PPARalpha -/- mice.
      Telemetric electrocardiography revealed neither atrio- nor intraventricular
      conduction defects in PPARalpha -/- mice. Also, heart rate, P-wave duration and
      amplitude, and QT interval were not affected. However, the amplitude of T wave
      from PPARalpha -/- mice was lower compared with wild-type (PPARalpha +/+) mice.
      When the myocardial function was measured by ex vivo Langendorff's heart
      preparation, basal and beta-adrenergic agonist-induced developed forces were
      significantly reduced in PPARalpha-null mice. In addition, Western blot analysis
      shows that the protein expression of beta1-adrenergic receptor is reduced in
      hearts from PPARalpha -/- mice. Histological analysis showed that hearts from
      PPARalpha -/- but not PPARalpha +/+ mice displayed myocardial fibrosis. These
      results suggest that PPARalpha-null mice have an alteration of cardiac
      contractile performance under basal and under stimulation of beta1-adrenergic
      receptors. These effects are associated with myocardial fibrosis. The data shed
      light on the role of PPARalpha in maintaining cardiac functions.

PMID- 16461374
TI  - Endothelial dysfunction and exercise performance in lone atrial fibrillation or
      associated with hypertension or diabetes: different results with cardioversion.
AB  - Endothelial dysfunction and underperfusion of exercising muscle contribute to
      exercise intolerance, hyperventilation, and breathlessness in atrial fibrillation
      (AF). Cardioversion (CV) improves endothelial function and exercise performance.
      We examined whether CV is equally beneficial in diabetes and hypertension,
      diseases that cause endothelial dysfunction and are often associated with AF.
      Cardiopulmonary exercise and pulmonary and endothelial (brachial artery flow
      mediated dilation) function were tested before and after CV in patients with AF
      alone (n = 18, group 1) or AF with hypertension (n = 19, group 2) or diabetes (n
      = 19, group 3). Compared with group 1, peak exercise workload, O2 consumption
      (Vo2), O2 pulse, aerobic efficiency (Delta Vo2/Delta WR), and ratio of brachial
      diameter changes to flow changes (Delta D/Delta F) were reduced in group 2 and,
      to a greater extent, in group 3; exercise ventilation efficiency (Ve/Vco2 slope)
      and dead space-to-tidal volume ratio (Vd/Vt) were similar among groups. CV had
      less effect on peak workload (+7% vs. +18%), peak Vo2 (+12% vs. +17%), O2 pulse
      (+33% vs. +50%), Delta Vo2/Delta WR (+7% vs. +12%), Ve/Vco2 slope (-6% vs. -12%),
      Delta D/Delta F (+7% vs. +10%), and breathlessness (Borg scale) in group 2 than
      in group 1 and was ineffective in group 3. The antioxidant vitamin C, tested in
      eight additional patients in each cohort, improved flow-mediated dilation in
      groups 1 and 2 before, but not after, CV and was ineffective in group 3,
      suggesting that the oxidative injury is least in lone AF, greater in hypertension
      with AF, and greater still in diabetes with AF. Comorbidities that impair
      endothelial activity worsen endothelial dysfunction and exercise intolerance in
      AF. The advantages of CV appear to be inversely related to the extent of the
      underlying oxidative injury.

PMID- 16461375
TI  - Evidence for absence of latch-bridge formation in muscular saphenous arteries.
AB  - Large-diameter elastic arteries can produce strong contractions indefinitely at a
      high-energy economy by the formation of latch bridges. Whether downstream blood
      vessels also use latch bridges remains unknown. The zero-pressure medial
      thickness and lumen diameter of rabbit saphenous artery (SA), a muscular branch
      of the elastic femoral artery (FA), were, respectively, approximately twofold and
      half-fold that of the FA. In isolated FA and SA rings, KCl rapidly (< 16 s)
      caused strong increases in isometric stress (1.2 x 10(5) N/m2) and intracellular
      Ca2+ concentration ([Ca2+]i; 250 nM). By 10 min, [Ca2+]i declined to
      approximately 175 nM in both tissues, but stress was sustained in FA (1.3 x 10(5)
      N/m2) and reduced by 40% in SA (0.8 x 10(5) N/m2). Reduced tonic stress
      correlated with reduced myosin light chain (MLC) phosphorylation in SA (28 vs.
      42% in FA), and simulations with the use of the four-state kinetic latch-bridge
      model supported the hypothesis that latch-bridge formation in FA, but not SA,
      permitted maintenance of high stress values at steady state. SA expressed more
      MLC phosphatase than FA, and permeabilized SA relaxed more rapidly than FA,
      suggesting that MLC phosphatase activity was greater in SA than in FA. The ratio
      of fast-to-slow myosin isoforms was greater for SA than FA, and on quick release,
      SA redeveloped isometric force faster than FA. These data support the hypothesis
      that maintained isometric force was 40% less in SA than in FA because expressed
      motor proteins in SA do not support latch-bridge formation.

PMID- 16461377
TI  - Ca2+ source-dependent transcription of CRE-containing genes in vascular smooth
      muscle.
AB  - Altered Ca2+ handling has immediate physiological and long-term genomic effects
      on vascular smooth muscle function. Previously we showed that Ca2+ entry through
      voltage-dependent Ca2+ channels (VDCCs) or store-operated Ca2+ channels (SOCCs)
      results in phosphorylation of the Ca2+/cAMP response element (CRE)-binding
      protein in cerebral arteries. Here, oligonucleotide array analysis was used to
      determine gene transcription profiles resulting from these two Ca2+ entry
      pathways in human cerebrovascular smooth muscle cell cultures. Results were
      confirmed and expanded using quantitative RT-PCR, Western blot, and
      immunofluorescence. A distinct, yet overlapping, set of CRE-regulated genes was
      induced by VDCC activation using K+ membrane depolarization vs. SOCC activation
      by thapsigargin (TG). Membrane depolarization selectively induced a sustained
      increase in early growth response-1 (Egr-1) mRNA and protein, which were
      inhibited by the VDCC blocker nimodipine and the SOCC inhibitor 2
      aminoethoxydiphenylborate (2-APB). TG selectively induced a sustained increase in
      MAPK phosphatase-1 (MKP-1) mRNA and protein, and these effects were decreased by
      2-APB, but not by nimodipine. The physiological agonist ANG II also stimulated
      expression of Egr-1 and MKP-1. Coadministration of 2-APB prevented expression of
      Egr-1 and MKP-1, whereas nimodipine blocked only Egr-1 expression. TG and ANG II
      induced phosphorylation of ERK, which was sensitive to 2-APB and was selectively
      required for CRE-binding protein phosphorylation. Our findings thus indicate that
      Ca2+ entry through VDCCs and store-operated Ca2+ entry can differentially
      regulate CRE-containing genes in vascular smooth muscle and also imply that
      agonist-induced signals involved in modulation of gene transcription can be
      controlled by multiple sources of Ca2+.

PMID- 16461376
TI  - Influence of sex and active muscle mass on renal vascular responses during static
      exercise.
AB  - During exercise, reflex renal vasoconstriction helps maintain blood pressure and
      redistributes blood flow to the contracting muscle. Sex and muscle mass have been
      shown to influence certain cardiovascular responses to exercise. Whether sex
      and/or muscle mass influence renal vasoconstrictor responses to exercise is
      unknown. We studied healthy men (n = 10) and women (n = 10) matched for age and
      body mass index during handgrip (HG, small muscle mass) and quadriceps
      contraction (QC, large muscle mass) as beat-to-beat changes in renal blood flow
      velocity (RBV; duplex ultrasound), mean arterial pressure (MAP; Finapres), and
      heart rate (ECG) were monitored. Renal vascular resistance (RVR) index was
      calculated as MAP / RBV. Responses to HG vs. QC were compared in 13 subjects. We
      found that 1) RVR responses to short (15-s) bouts and fatiguing HG were similar
      in men and women (change in RVR during 15-s HG at 70% of maximum voluntary
      contraction = 23 +/- 4 and 31 +/- 4% in men and women, respectively, P = not
      significant); 2) post-HG circulatory responses were similar in men and women; and
      3) HG and QC were similar during short (15-s) bouts (change in RVR during HG at
      50% of maximum voluntary contraction = 19 +/- 3 and 18 +/- 5% for arm and leg,
      respectively, P = not significant). Our findings suggest that muscle reflex
      mediated renal vasoconstriction is similar in men and women during static
      exercise. Moreover, muscle mass does not contribute to the magnitude of the
      reflex renal vasoconstrictor response seen with muscle contraction.

PMID- 16461378
TI  - Posttranslational regulation of nitrate reductase strongly affects the levels of
      free amino acids and nitrate, whereas transcriptional regulation has only minor
      influence.
AB  - Diurnal variations in nitrate reductase (NR) activity and nitrogen metabolites
      were examined in wild-type Nicotiana plumbaginifolia and transformants with
      various degrees of NR deregulation. In the C1 line, NR was only deregulated at
      the transcriptional level by placing the NR gene under the control of the
      cauliflower mosaic virus 35S RNA promoter. In the Del8 and S521D lines, NR was
      additionally deregulated at the posttranslational level either by a deletion
      mutation in the N-terminal domain or by a mutation of the regulatory
      phosphorylation site (serine-521). Posttranslational regulation was essential for
      pronounced diurnal variations in NR activity. Low nitrate content was related to
      deregulation of NR, whereas the level of total free amino acids was much higher
      in plants with fully deregulated NR. Abolishing transcriptional and
      posttranslational regulation (S521D plants) resulted in an increase of glutamine
      and asparagine by a factor of 9 and 14, respectively, compared with wild type,
      whereas abolishing transcriptional regulation (C1 plants) only resulted in
      increases of glutamine and asparagine by factors <2. Among the minor amino acids,
      isoleucine and threonine, in particular, showed enhanced levels in S521D. Nitrate
      uptake rates were the same in S521D and wild type as determined with (15)N
      feeding. Deregulation of NR appears to set the level of certain amino acids,
      whereas diurnal variations were still determined by light/dark. Generally,
      deregulation of NR at the transcriptional level did not have much influence on
      metabolite levels, but additional deregulation at the posttranslational level
      resulted in profound changes of nitrogen metabolite levels.

PMID- 16461379
TI  - Protein profiling of plastoglobules in chloroplasts and chromoplasts. A
      surprising site for differential accumulation of metabolic enzymes.
AB  - Plastoglobules (PGs) are oval or tubular lipid-rich structures present in all
      plastid types, but their specific functions are unclear. PGs contain quinones,
      alpha-tocopherol, and lipids and, in chromoplasts, carotenoids as well. It is not
      known whether PGs contain any enzymes or regulatory proteins. Here, we determined
      the proteome of PGs from chloroplasts of stressed and unstressed leaves of
      Arabidopsis (Arabidopsis thaliana) as well as from pepper (Capsicum annuum) fruit
      chromoplasts using mass spectrometry. Together, this showed that the proteome of
      chloroplast PGs consists of seven fibrillins, providing a protein coat and
      preventing coalescence of the PGs, and an additional 25 proteins likely involved
      in metabolism of isoprenoid-derived molecules (quinines and tocochromanols),
      lipids, and carotenoid cleavage. Four unknown ABC1 kinases were identified,
      possibly involved in regulation of quinone monooxygenases. Most proteins have not
      been observed earlier but have predicted N-terminal chloroplast transit peptides
      and lack transmembrane domains, consistent with localization in the PG lipid
      monolayer particles. Quantitative differences in PG composition in response to
      high light stress and degreening were determined by differential stable-isotope
      labeling using formaldehyde. More than 20 proteins were identified in the PG
      proteome of pepper chromoplasts, including four enzymes of carotenoid
      biosynthesis and several homologs of proteins observed in the chloroplast PGs.
      Our data strongly suggest that PGs in chloroplasts form a functional metabolic
      link between the inner envelope and thylakoid membranes and play a role in
      breakdown of carotenoids and oxidative stress defense, whereas PGs in
      chromoplasts are also an active site for carotenoid conversions.

PMID- 16461380
TI  - AtATM3 is involved in heavy metal resistance in Arabidopsis.
AB  - AtATM3, an ATP-binding cassette transporter of Arabidopsis (Arabidopsis
      thaliana), is a mitochondrial protein involved in the biogenesis of iron-sulfur
      clusters and iron homeostasis in plants. Our gene expression analysis showed that
      AtATM3 is up-regulated in roots of plants treated with cadmium [Cd(II)] or lead
      (II); hence, we investigated whether this gene is involved in heavy metal
      tolerance. We found that AtATM3-overexpressing plants were enhanced in resistance
      to Cd, whereas atatm3 mutant plants were more sensitive to Cd than their wild
      type controls. Moreover, atatm3 mutant plants expressing 35S promoter-driven
      AtATM3 were more resistant to Cd than wild-type plants. Since previous reports
      often showed that the cytosolic glutathione level is positively correlated with
      heavy metal resistance, we measured nonprotein thiols (NPSH) in these mutant
      plants. Surprisingly, we found that atatm3 contained more NPSH than the wild type
      under normal conditions. AtATM3-overexpressing plants did not differ under normal
      conditions, but contained less NPSH than wild-type plants when exposed to Cd(II).
      These results suggest a role for AtATM3 in regulating cellular NPSH level, a
      hypothesis that was further supported by our gene expression study. Genetic or
      pharmacological inhibition of glutathione biosynthesis led to the elevated
      expression of AtATM3, whereas expression of the glutathione synthase gene GSH1
      was increased under Cd(II) stress and in the atatm3 mutant. Because the closest
      homolog of AtATM3 in fission yeast (Schizosaccharomyces pombe), HMT1, is a
      vacuolar membrane-localized phytochelatin-Cd transporter, it is tempting to
      speculate that glutathione-Cd(II) complexes formed in the mitochondria are
      exported by AtATM3. In conclusion, our data show that AtATM3 contributes to Cd
      resistance and suggest that it may mediate transport of glutamine synthetase
      conjugated Cd(II) across the mitochondrial membrane.

PMID- 16461381
TI  - Silencing of a germin-like gene in Nicotiana attenuata improves performance of
      native herbivores.
AB  - Germins and germin-like proteins (GLPs) are known to function in pathogen
      resistance, but their involvement in defense against insect herbivores is poorly
      understood. In the native tobacco Nicotiana attenuata, attack from the specialist
      herbivore Manduca sexta or elicitation by adding larval oral secretions (OS) to
      wounds up-regulates transcripts of a GLP. To understand the function of this
      gene, which occurs as a single copy, we cloned the full-length NaGLP and silenced
      its expression in N. attenuata by expressing a 250-bp fragment in an antisense
      orientation with an Agrobacterium-based transformation system and by virus
      induced gene silencing (VIGS). Homozygous lines harboring a single insert and
      VIGS plants had significantly reduced constitutive (measured in roots) and
      elicited NaGLP transcript levels (in leaves). Silencing NaGLP improved M. sexta
      larval performance and Tupiocoris notatus preference, two native herbivores of N.
      attenuata. Silencing NaGLP also attenuated the OS-induced hydrogen peroxide
      (H(2)O(2)), diterpene glycosides, and trypsin proteinase inhibitor responses,
      which may explain the observed susceptibility of antisense or VIGS plants to
      herbivore attack and increased nicotine contents, but did not influence the OS
      elicited jasmonate and salicylate bursts, or the release of the volatile organic
      compounds (limonene, cis-alpha-bergamotene, and germacrene-A) that function as an
      indirect defense. This suggests that NaGLP is involved in H(2)O(2) production and
      might also be related to ethylene production and/or perception, which in turn
      influences the defense responses of N. attenuata via H(2)O(2) and ethylene
      signaling pathways.

PMID- 16461382
TI  - Point mutations with positive selection were a major force during the evolution
      of a receptor-kinase resistance gene family of rice.
AB  - The rice (Oryza sativa) Xa26 gene, which confers resistance to bacterial blight
      disease and encodes a leucine-rich repeat (LRR) receptor kinase, resides at a
      locus clustered with tandem homologous genes. To investigate the evolution of
      this family, four haplotypes from the two subspecies of rice, indica and
      japonica, were analyzed. Comparative sequence analysis of 34 genes of 10 types of
      paralogs of the family revealed haplotype polymorphisms and pronounced paralog
      diversity. The orthologs in different haplotypes were more similar than the
      paralogs in the same haplotype. At least five types of paralogs were formed
      before the separation of indica and japonica subspecies. Only 7% of amino acid
      sites were detected to be under positive selection, which occurred in the
      extracytoplasmic domain. Approximately 74% of the positively selected sites were
      solvent-exposed amino acid residues of the LRR domain that have been proposed to
      be involved in pathogen recognition, and 73% of the hypervariable sites detected
      in the LRR domain were subject to positive selection. The family is formed by
      tandem duplication followed by diversification through recombination, deletion,
      and point mutation. Most variation among genes in the family is caused by point
      mutations and positive selection.

PMID- 16461383
TI  - A role for auxin response factor 19 in auxin and ethylene signaling in
      Arabidopsis.
AB  - Although auxin response factors (ARFs) are the first well-characterized proteins
      that bind to the auxin response elements, elucidation of the roles of each ARF
      gene in auxin responses and plant development has been challenging. Here we show
      that ARF19 and ARF7 not only participate in auxin signaling, but also play a
      critical role in ethylene responses in Arabidopsis (Arabidopsis thaliana) roots,
      indicating that the ARFs serve as a cross talk point between the two hormones.
      Both arf19 and arf7 mutants isolated from our forward genetic screens are auxin
      resistant and the arf19arf7 double mutant had stronger auxin resistance than the
      single mutants and displayed phenotypes not seen in the single mutants.
      Furthermore, we show that a genomic fragment of ARF19 not only complements arf19,
      but also rescues arf7. We conclude that ARF19 complements ARF7 at the protein
      level and that the ARF7 target sequences are also recognized by ARF19. Therefore,
      it is the differences in expression level/pattern and not the differences in
      protein sequences between the two ARFs that determines the relative contribution
      of the two ARFs in auxin signaling and plant development. In addition to being
      auxin resistant, arf19 has also ethylene-insensitive roots and ARF19 expression
      is induced by ethylene treatment. This work provides a sensitive genetic screen
      for uncovering auxin-resistant mutants including the described arf mutants. This
      study also provides a likely mechanism for coordination and integration of
      hormonal signals to regulate plant growth and development.

PMID- 16461384
TI  - Cholic acid, a bile acid elicitor of hypersensitive cell death, pathogenesis
      related protein synthesis, and phytoalexin accumulation in rice.
AB  - When plants interact with certain pathogens, they protect themselves by
      generating various defense responses. These defense responses are induced by
      molecules called elicitors. Since long ago, composts fermented by animal feces
      have been used as a fertilizer in plant cultivation, and recently, have been
      known to provide suppression of plant disease. Therefore, we hypothesized that
      the compounds from animal feces may function as elicitors of plant defense
      responses. As a result of examination of our hypothesis, an elicitor of rice
      defense responses was isolated from human feces, and its structure was identified
      as cholic acid (CA), a primary bile acid in animals. Treatment of rice (Oryza
      sativa) leaves with CA induced the accumulation of antimicrobial compounds
      (phytoalexins), hypersensitive cell death, pathogenesis-related (PR) protein
      synthesis, and increased resistance to subsequent infection by virulent
      pathogens. CA induced these defense responses more rapidly than did fungal
      cerebroside, a sphingolipid elicitor isolated from the rice pathogenic fungus
      Magnaporthe grisea. Furthermore, fungal cerebroside induced both types of rice
      phytoalexins, phytocassanes and momilactones, whereas CA mainly induced
      phytocassanes, but not momilactones. In the structure-activity relationship
      analysis, the hydroxyl groups at C-7 and C-12, and the carboxyl group at C-24 of
      CA contributed to the elicitor activity. These results indicate that CA is
      specifically recognized by rice and is a different type of elicitor from fungal
      cerebroside. This report demonstrated that bile acid induced defense responses in
      plants.

PMID- 16461385
TI  - The geminivirus nuclear shuttle protein NSP inhibits the activity of AtNSI, a
      vascular-expressed Arabidopsis acetyltransferase regulated with the sink-to
      source transition.
AB  - DNA viruses can suppress or enhance the activity of cellular acetyltransferases
      to regulate virus gene expression and to affect cell cycle progression in support
      of virus replication. A role for protein acetylation in regulating the nuclear
      export of the bipartite geminivirus (Begomovirus) DNA genome was recently
      suggested by the findings that the viral movement protein NSP, a nuclear shuttle
      protein, interacts with the Arabidopsis (Arabidopsis thaliana) nuclear
      acetyltransferase AtNSI (nuclear shuttle protein interactor), and that this
      interaction and NSI expression are necessary for cabbage leaf curl virus
      infection and pathogenicity. To further investigate the consequences of NSI-NSP
      interactions, and the potential role of NSI in Arabidopsis growth and
      development, we used a reverse yeast two-hybrid selection and deletion analysis
      to identify NSI mutants that failed to interact with NSP, and promoter fusions to
      a uidA reporter gene to analyze the pattern of NSI expression during plant
      development. We found that NSI self assembles into highly active enzyme complexes
      and that high concentrations of NSP, in the absence of viral DNA, can inhibit NSI
      activity in vitro. Based on our detailed analysis of three NSI missense mutants,
      we identified an 88-amino acid putative domain, which spans NSI residues 107 to
      194, as being required for both NSI oligomerization and its interaction with NSP.
      Finally, we found that NSI is predominantly transcribed in vascular cells, and
      that its expression is developmentally regulated in a manner that resembles the
      sink-to-source transition. Our data indicate that NSP can inhibit NSI activity by
      interfering with its assembly into highly active complexes, and suggest a
      mechanism by which NSP can both recruit NSI to regulate nuclear export of the
      viral genome and down-regulate NSI activity on cellular targets, perhaps to
      affect cellular differentiation and favor virus replication.

PMID- 16461386
TI  - Contribution of the alternative pathway to respiration during thermogenesis in
      flowers of the sacred lotus.
AB  - We report results from in vivo measurements, using oxygen isotope discrimination
      techniques, of fluxes through the alternative and cytochrome respiratory pathways
      in thermogenic plant tissue, the floral receptacle of the sacred lotus (Nelumbo
      nucifera). Fluxes through both pathways were measured in thermoregulating flowers
      undergoing varying degrees of thermogenesis in response to ambient temperature.
      Significant increases in alternative pathway flux were found in lotus receptacles
      with temperatures 16 degrees C to 20 degrees C above ambient, but not in those
      with lesser amounts of heating. Alternative pathway flux in the hottest
      receptacles was 75% of the total respiratory flux. In contrast, fluxes through
      the cytochrome pathway did not change significantly during thermogenesis. These
      data support the hypothesis that increased flux through the alternative pathway
      is responsible for heating in the lotus and that it is unlikely that uncoupling
      proteins, which would have produced increased fluxes through the cytochrome
      pathway, contribute significantly to heating in this tissue. Comparisons of
      actual flux, with capacity determined using inhibitors, suggested that the
      alternative pathway was operating at close to maximum capacity in heating tissues
      of lotus. However, in nonheating tissues the inhibitor data significantly
      overestimated the alternative pathway flux. This confirms that isotopic
      measurements are necessary for accurate determination of fluxes through the two
      pathways.

PMID- 16461387
TI  - An ankyrin repeat-containing protein, characterized as a ubiquitin ligase, is
      closely associated with membrane-enclosed organelles and required for pollen
      germination and pollen tube growth in lily.
AB  - Exhibiting rapid polarized growth, the pollen tube delivers the male gametes into
      the ovule for fertilization in higher plants. To get an overall picture of gene
      expression during pollen germination and pollen tube growth, we profiled the
      transcription patterns of 1,536 pollen cDNAs from lily (Lilium longiflorum) by
      microarray. Among those that exhibited significant differential expression, a
      cDNA named lily ankyrin repeat-containing protein (LlANK) was thoroughly studied.
      The full-length LlANK cDNA sequence predicts a protein containing five tandem
      ankyrin repeats and a RING zinc-finger domain. The LlANK protein possesses
      ubiquitin ligase activity in vitro. RNA blots demonstrated that LlANK transcript
      is present in mature pollen and its level, interestingly contrary to most pollen
      mRNAs, up-regulated significantly during pollen germination and pollen tube
      growth. When fused with green fluorescent protein and transiently expressed in
      pollen, LlANK was found dominantly associated with membrane-enclosed organelles
      as well as the generative cell. Overexpression of LlANK, however, led to abnormal
      growth of the pollen tube. On the other hand, transient silencing of LlANK
      impaired pollen germination and tube growth. Taken together, these results showed
      that LlANK is a ubiquitin ligase associated with membrane-enclosed organelles and
      required for polarized pollen tube growth.

PMID- 16461389
TI  - Comparative analysis of the heat stable proteome of radicles of Medicago
      truncatula seeds during germination identifies late embryogenesis abundant
      proteins associated with desiccation tolerance.
AB  - A proteomic analysis was performed on the heat stable protein fraction of imbibed
      radicles of Medicago truncatula seeds to investigate whether proteins can be
      identified that are specifically linked to desiccation tolerance (DT). Radicles
      were compared before and after emergence (2.8 mm long) in association with the
      loss of DT, and after reinduction of DT by an osmotic treatment. To separate
      proteins induced by the osmotic treatment from those linked with DT, the
      comparison was extended to 5 mm long emerged radicles for which DT could no
      longer be reinduced, albeit that drought tolerance was increased. The abundance
      of 15 polypeptides was linked with DT, out of which 11 were identified as late
      embryogenesis abundant proteins from different groups: MtEm6 (group 1), one
      isoform of DHN3 (dehydrins), MtPM25 (group 5), and three members of group 3 (MP2,
      an isoform of PM18, and all the isoforms of SBP65). In silico analysis revealed
      that their expression is likely seed specific, except for DHN3. Other isoforms of
      DNH3 and PM18 as well as three isoforms of the dehydrin Budcar5 were associated
      with drought tolerance. Changes in the abundance of MtEm6 and MtPM25 in imbibed
      cotyledons during the loss of DT and in developing embryos during the acquisition
      of DT confirmed the link of these two proteins with DT. Fourier transform
      infrared spectroscopy revealed that the recombinant MtPM25 and MtEm6 exhibited a
      certain degree of order in the hydrated state, but that they became more
      structured by adopting alpha helices and beta sheets during drying. A model is
      presented in which DT-linked late embryogenesis abundant proteins might exert
      different protective functions at high and low hydration levels.

PMID- 16461388
TI  - Analysis of phase of LUCIFERASE expression reveals novel circadian quantitative
      trait loci in Arabidopsis.
AB  - In response to exogenous rhythms of light and temperature, most organisms exhibit
      endogenous circadian rhythms (i.e. cycles of behavior and gene expression with a
      periodicity of approximately 24 h). One of the defining characteristics of the
      circadian clock is its ability to synchronize (entrain) to an environmental
      rhythm. Entrainment is arguably the most salient feature of the clock in
      evolutionary terms. Previous quantitative trait studies of circadian
      characteristics in Arabidopsis (Arabidopsis thaliana) considered leaf movement
      under constant (free-running) conditions. This study, however, addressed the
      important circadian parameter of phase, which reflects the entrained relationship
      between the clock and the external cycle. Here it is shown that, when exposed to
      the same photoperiod, Arabidopsis accessions differ dramatically in phase.
      Variation in the timing of circadian LUCIFERASE expression was used to map loci
      affecting the entrained phase of the clock in a recombinant population derived
      from two geographically distant accessions, Landsberg erecta and Cape Verde
      Islands. Four quantitative trait loci (QTL) were found with major effects on
      circadian phase. A QTL on chromosome 5 contained SIGNALING IN RED LIGHT REDUCED 1
      and PSEUDORESPONSE REGULATOR 3, both genes known to affect the circadian clock.
      Previously unknown polymorphisms were found in both genes, making them candidates
      for the effect on phase. Fine mapping of two other QTL highlighted genomic
      regions not previously identified in any circadian screens, indicating their
      effects are likely due to genes not hitherto considered part of the circadian
      system.

PMID- 16461390
TI  - Dimethylallyl diphosphate and geranyl diphosphate pools of plant species
      characterized by different isoprenoid emissions.
AB  - Dimethylallyl diphosphate (DMADP) and geranyl diphosphate (GDP) are the last
      precursors of isoprene and monoterpenes emitted by leaves, respectively. DMADP
      and GDP pools were measured in leaves of plants emitting isoprene (Populus alba),
      monoterpenes (Quercus ilex and Mentha piperita), or nonemitting isoprenoids
      (Prunus persica). Detectable pools were found in all plant species, but P.
      persica showed the lowest pool size, which indicates a limitation of the whole
      pathway leading to isoprenoid biosynthesis in nonemitting species. The pools of
      DMADP and GDP of nonemitting, isoprene-emitting, and monoterpene-emitting species
      were partially labeled (generally 40%-60% of total carbon-incorporated (13)C)
      within the same time by which volatile isoprenoids are fully labeled (15 min).
      This indicates the coexistence of two pools for both precursors, the rapidly
      labeled pool presumably occurring in chloroplasts and thereby synthesized by the
      methylerythritol phosphate pathway and the nonlabeled pool presumably located in
      the cytosol and synthesized by the mevalonic pathway. In M. piperita storing
      monoterpenes in specialized leaf structures, the GDP pool remained totally
      unlabeled, indicating either that monoterpenes are totally formed by the
      mevalonic pathway or that labeling occurs slowly in comparison to the large pool
      of stored monoterpenes in this plant. The pools of DMADP and GDP increased during
      the season (from May to July) but decreased when the leaf was darkened or exposed
      to very high temperature. In the dark, the pool of DMADP of the isoprene-emitting
      species decreased faster than the pool of GDP. However, after 6 h of darkness,
      both pools were depleted to about 10% of the pool size in illuminated leaves.
      This indicates that both the chloroplastic and the cytosolic pools of precursors
      are depleted in the dark. When comparing measurements over the season and at
      different temperatures, an inverse correlation was observed between isoprene
      emission by P. alba and the DMADP pool size and between monoterpene emission by
      Q. ilex and the GDP pool size. This suggests that the pool size does not limit
      the emission of isoprenoids. Rather, it indicates that the flux of volatile
      isoprenoids effectively controls the size of their pools of precursors.

PMID- 16461391
TI  - Matrices with compliance comparable to that of brain tissue select neuronal over
      glial growth in mixed cortical cultures.
AB  - Cortical neurons and astrocytes respond strongly to changes in matrix rigidity
      when cultured on flexible substrates. In this study, existing polyacrylamide gel
      polymerization methods were modified into a novel method for making substrates
      capable of engaging specific cell-adhesion receptors. Embryonic cortical
      dissociations were cultured on polyacrylamide or fibrin gel scaffolds of varying
      compliance. On soft gels, astrocytes do not spread and have disorganized F-actin
      compared to the cytoskeletons of astrocytes on hard surfaces. Neurons, however,
      extend long neurites and polymerize actin filaments on both soft and hard gels.
      Compared to tissue culture plastic or stiff gel substrates coated with laminin,
      on which astrocytes overgrow neurons in mixed cultures, laminin-coated soft gels
      encourage attachment and growth of neurons while suppressing astrocyte growth.
      The number of astrocytes on soft gels is lower than on hard even in the absence
      of mitotic inhibitors normally used to temper the astrocyte population.
      Dissociated embryonic rat cortices grown on flexible fibrin gels, a biomaterial
      with potential use as an implant material, display a similar mechano-dependent
      difference in cell population. The stiffness of materials required for optimal
      neuronal growth, characterized by an elastic modulus of several hundred Pa, is in
      the range measured for intact rat brain. Together, these data emphasize the
      potential importance of material substrate stiffness as a design feature in the
      next generation of biomaterials intended to promote neuronal regeneration across
      a lesion in the central nervous system while simultaneously minimizing the
      ingrowth of astrocytes into the lesion area.

PMID- 16461392
TI  - Phase behavior of lipid monolayers containing DPPC and cholesterol analogs.
AB  - We investigate the miscibility phase behavior of lipid monolayers containing a
      wide variety of sterols. Six of the sterols satisfy a definition from an earlier
      study of "membrane-active sterols" in bilayers (cholesterol, epicholesterol,
      lathosterol, dihydrocholesterol, ergosterol, and desmosterol), and six do not (25
      hydroxycholesterol, lanosterol, androstenolone, coprostanol, cholestane, and
      cholestenone). We find that monolayers containing dipalmitoyl phosphatidylcholine
      mixed with membrane-active sterols generally produce phase diagrams containing
      two distinct regions of immiscible liquid phases, whereas those with membrane
      inactive sterols generally do not. This observation establishes a correlation
      between lipid monolayers and bilayers. It also demonstrates that the ability to
      form two regions of immiscibility in monolayers is not one of the biophysical
      attributes that explains cholesterol's predominance in animal cell membranes.
      Furthermore, we find unusual phase behavior for dipalmitoyl phosphatidylcholine
      monolayers containing 25-hydroxycholesterol, which produce both an upper and a
      lower miscibility transition. The lower transition correlates with a sharp change
      of slope in the pressure-area isotherm.

PMID- 16461394
TI  - A master relation defines the nonlinear viscoelasticity of single fibroblasts.
AB  - Cell mechanical functions such as locomotion, contraction, and division are
      controlled by the cytoskeleton, a dynamic biopolymer network whose mechanical
      properties remain poorly understood. We perform single-cell uniaxial stretching
      experiments on 3T3 fibroblasts. By superimposing small amplitude oscillations on
      a mechanically prestressed cell, we find a transition from linear viscoelastic
      behavior to power law stress stiffening. Data from different cells over several
      stress decades can be uniquely scaled to obtain a master relation between the
      viscoelastic moduli and the average force. Remarkably, this relation holds
      independently of deformation history, adhesion biochemistry, and intensity of
      active contraction. In particular, it is irrelevant whether force is actively
      generated by the cell or externally imposed by stretching. We propose that the
      master relation reflects the mechanical behavior of the force-bearing actin
      cytoskeleton, in agreement with stress stiffening known from semiflexible
      filament networks.

PMID- 16461393
TI  - Zero mode waveguides for single-molecule spectroscopy on lipid membranes.
AB  - Zero mode waveguides (ZMWs), subwavelength optical nanostructures with dimensions
      ranging from 50 to 200 nm, have been used to study systems involving ligand
      receptor interactions. We show that under proper conditions, lipid membranes will
      invaginate into the nanostructures, which confine optical excitation to
      subattoliter volumes. Fluorescence correlation spectroscopy (FCS) was used to
      characterize the diffusion of fluorescently tagged lipids in liquid-disordered
      phase 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and gel phase 1,2
      distearoyl-sn-glycero-3-phosphocholine (DSPC) membranes incubated on the
      nanostructured surface. In contrast to the POPC, DSPC membranes did not appear to
      enter the structures, suggesting that invagination is dependent on membrane
      rigidity. Although correlation curves obtained from POPC membranes conformed to
      previously derived models for diffusion in the evanescent field within the
      nanostructure, the diffusion constants obtained were systematically lower than
      expected. The validity of the one-dimensional diffusion model for membrane
      diffusion is discussed and it is concluded that the erroneous diffusion constants
      are a result of nontrivial membrane conformation within the ZMWs. Additionally,
      FCS was used to characterize the fraction of fluorescently labeled tetanus toxin
      C fragment bound to a ganglioside-populated POPC membrane within the ZMWs. This
      allowed the determination of the toxin's equilibrium binding constant at a
      concentration of 500 nM; higher than possible with diffraction-limited FCS. To
      our knowledge, the results presented here are the first reported for supported
      lipid bilayers in nanostructured devices. Furthermore, they open the possibility
      of studying membrane imbedded receptors and proteins at physiological
      concentrations with single-molecule resolution.

PMID- 16461395
TI  - Gas phase characterization of the noncovalent quaternary structure of cholera
      toxin and the cholera toxin B subunit pentamer.
AB  - Cholera toxin (CTx) is an AB5 cytotonic protein that has medical relevance in
      cholera and as a novel mucosal adjuvant. Here, we report an analysis of the
      noncovalent homopentameric complex of CTx B chain (CTx B5) using electrospray
      ionization triple quadrupole mass spectrometry and tandem mass spectrometry and
      the analysis of the noncovalent hexameric holotoxin usingelectrospray ionization
      time-of-flight mass spectrometry over a range of pH values that correlate with
      those encountered by this toxin after cellular uptake. We show that noncovalent
      interactions within the toxin assemblies were maintained under both acidic and
      neutral conditions in the gas phase. However, unlike the related Escherichia coli
      Shiga-like toxin B5 pentamer (SLTx B), the CTx B5 pentamer was stable at low pH,
      indicating that additional interactions must be present within the latter.
      Structural comparison of the CTx B monomer interface reveals an additional alpha
      helix that is absent in the SLTx B monomer. In silico energy calculations support
      interactions between this helix and the adjacent monomer. These data provide
      insight into the apparent stabilization of CTx B relative to SLTx B.

PMID- 16461396
TI  - ANS fluorescence detects widespread perturbations of protein tertiary structure
      in ice.
AB  - Freeze-induced perturbations of the protein native fold are poorly understood
      owing to the difficulty of monitoring their structure in ice. Here, we report
      that binding of the fluorescence probe 1-anilino-8-naphthalene sulfonate (ANS) to
      proteins in ice can provide a general monitor of ice-induced alterations of their
      tertiary structure. Experiments conducted with copper-free azurin from
      Pseudomonas aeruginosa and mutants I7S, F110S, and C3A/C26A correlate the
      magnitude of the ice-induced perturbation, as inferred from the extent of ANS
      binding, to the plasticity of the globular fold, increasing with less stable
      globular folds as well as when the flexibility of the macromolecule is enhanced.
      The distortion of the native structure inferred from ANS binding was found to
      draw a parallel with the extent of irreversible denaturation by freeze-thawing,
      suggesting that these altered conformations play a direct role on freeze damage.
      ANS binding experiments, extended to a set of proteins including serum albumin,
      alpha-amylase, beta-galactosidase, alcohol dehydrogenase from horse liver,
      alcohol dehydrogenase from yeast, lactic dehydrogenase, and aldolase, confirmed
      that a stressed condition of the native fold in the frozen state appears to be
      general to most proteins and pointed out that oligomers tend to be more labile
      than monomers presumably because the globular fold can be further destabilized by
      subunit dissociation. The results of this study suggest that the ANS binding
      method may find practical utility in testing the effectiveness of various
      additives employed in protein formulations as well as to devise safer freeze
      drying protocols of pharmaceutical proteins.

PMID- 16461397
TI  - Monitoring single-stranded DNA secondary structure formation by determining the
      topological state of DNA catenanes.
AB  - Single-stranded DNA (ssDNA) has essential biological functions during DNA
      replication, recombination, repair, and transcription. The structure of ssDNA
      must be better understood to elucidate its functions. However, the available data
      are too limited to give a clear picture of ssDNA due to the extremely capricious
      structural features of ssDNA. In this study, by forming DNA catenanes and
      determining their topology (the linking number, Lk) through the electrophoretic
      analysis, we demonstrate that the studies of catenanes formed from two ssDNA
      molecules can yield valuable new information about the ssDNA secondary structure.
      We construct catenanes out of two short (60/70 nt) ssDNA molecules by enzymatic
      cyclization of linear oligodeoxynucleotides. The secondary structure formed
      between the two DNA circles determines the topology (the Lk value) of the
      constructed DNA catenane. Thus, formation of the secondary structure is
      experimentally monitored by observing the changes of linking number with
      sequences and conditions. We found that the secondary structure of ssDNA is much
      easier to form than expected: the two strands in an internal loop in the folded
      ssDNA structure prefer to braid around each other rather than stay separately
      forming a loop, and a duplex containing only mismatched basepairs can form under
      physiological conditions.

PMID- 16461398
TI  - Dynamical determinants of drug-inducible gene expression in a single bacterium.
AB  - A primitive example of adaptation in gene expression is the balance between the
      rate of synthesis and degradation of cellular RNA, which allows rapid responses
      to environmental signals. Here, we investigate how multidrug efflux pump systems
      mediate the dynamics of a simple drug-inducible system in response to a steady
      level of inducer. Using fluorescence correlation spectroscopy, we measured in
      real time within a single bacterium the transcription activity at the RNA level
      of the acrAB-TolC multidrug efflux pump system. When cells are exposed to
      constant level of anhydrotetracycline inducer and are adsorbed onto a poly-L
      lysine-coated surface, we found that the acrAB-TolC promoter is steadily active.
      We also monitored the activity of the tet promoter to characterize the effect of
      this efflux system on the dynamics of drug-inducible transcription. We found that
      the transcriptional response of the tet promoter to a steady level of aTc rises
      and then falls back to its preinduction level. The rate of RNA degradation was
      constant throughout the transcriptional pulse, indicating that the modulation of
      intracellular inducer concentration alone can produce this pulsating response.
      Single-cell experiments together with numerical simulations suggest that such
      pulsating response in drug-inducible genetic systems is a property emerging from
      the dependence of drug-inducible transcription on multidrug efflux systems.

PMID- 16461399
TI  - Size, motion, and function of the SecY translocon revealed by molecular dynamics
      simulations with virtual probes.
AB  - We report a hybrid, coarse-grained and atomistic, molecular dynamics simulation
      study of the size, motion, and function of the SecY protein-conducting channel.
      Growing and pushing virtual soft ball constructs through the pore of SecY, we
      mimic the push-through of polypeptides, performed cotranslationally by the
      ribosome and posttranslationally by the SecA ATPase. Forced lateral opening of a
      "front gate" between transmembrane helices is also induced by the passage of the
      virtual probes, with implications for the membrane insertion of peptides. We
      conclude that the SecY channel can stretch to allow passage of peptides with
      transversal sizes of approximately 16 A. The observed motion of a transmembrane
      helical "plug" controlling the closed and open states of the channel is
      consistent with experimental results and confirms previous hypotheses.
      Additionally, the "hinge" region for front gate opening is observed to be highly
      mobile as postulated. Both the forced dilation of a "ring" of residues at the
      middle of the pore and the lateral opening of the front gate are shown to induce
      plug displacement, but neither accomplish a full-extent motion of the plug to the
      back of the channel. For probes whose passage does not destroy the resilience of
      the SecY, both lateral exit and full translocation are observed, despite the fact
      that applied forces were always in the direction along the pore axis. Lateral
      exit is accompanied by front gate opening and slight plug displacement, whereas
      full translocation is accompanied by large plug displacement but no apparent
      lateral opening. Simulations also reveal that dilating the pore ring is a more
      effective way to destabilize the plug than intercalation of a cylinder-like probe
      at the front gate. Based on the simulations, the existence of a family of diverse
      open states is proposed.

PMID- 16461400
TI  - Toward the understanding of MNEI sweetness from hydration map surfaces.
AB  - The binding mechanism of sweet proteins to their receptor, a G-protein-coupled
      receptor, is not supported by direct structural information. In principle, the
      key groups responsible for biological activity (glucophores) can be localized on
      a small structural unit (sweet finger) or spread on a larger surface area. A
      recently proposed model, called "wedge model", implies a large surface of
      interaction with the receptor. To explore this model in greater detail, it is
      necessary to examine the physicochemical features of the surfaces of sweet
      proteins, since their interaction with the receptor, with respect to that of
      small sweeteners, is more dependent on general physicochemical properties of the
      interface, such as electrostatic potential and hydration. In this study, we
      performed exhaustive molecular dynamics simulations in explicit water of the
      sweet protein MNEI and of its structural mutant G-16A, whose sweetness is one
      order of magnitude lower than that of MNEI. Solvent density and self-diffusion
      calculated from molecular dynamics simulations suggest a likely area of
      interaction delimited by four stretches arranged as a tetrahedron whose shape is
      complementary to that of a cavity on the surface of the receptor, in agreement
      with the wedge model. The suggested area of interaction is amazingly consistent
      with known mutagenesis data. In addition, the asymmetric hydration of the only
      helix in both proteins hints at a specific role for this secondary structure
      element in orienting the protein during the binding process.

PMID- 16461401
TI  - The contribution of transient counterion imbalances to DNA bending fluctuations.
AB  - A two-sided model for DNA is employed to analyze fluctuations of the spatial
      distribution of condensed counterions and the effect of these fluctuations on
      transient bending. We analyze two classes of fluctuations. In the first, the
      number of condensed counterions on one side of the DNA remains at its average
      value, while on the other side, counterions are lost to bulk solution or gained
      from it. The second class of fluctuations is characterized by movement of some
      counterions from one side of the DNA to the other. The root-mean-square
      fluctuation for each class is calculated from counterion condensation theory. The
      amplitude of the root-mean-square fluctuation depends on the ionic strength as
      well as the length of the segment considered and is of the order 5-10%. Both
      classes of fluctuation result in transient bends toward the side of greater
      counterion density. The bending amplitudes are approximately 15% of the total
      root-mean-square bends associated with the persistence length of DNA. We are thus
      led to suggest that asymmetric fluctuations of counterion density contribute
      modestly but significantly toward the aggregate of thermalized solvent
      fluctuations that cause bending deformations of DNA free in solution. The
      calculations support the idea that counterions may exert some modulating
      influence on the fine structure of DNA.

PMID- 16461402
TI  - How proteins search for their specific sites on DNA: the role of DNA
      conformation.
AB  - It is known since the early days of molecular biology that proteins locate their
      specific targets on DNA up to two orders-of-magnitude faster than the
      Smoluchowski three-dimensional diffusion rate. An accepted explanation of this
      fact is that proteins are nonspecifically adsorbed on DNA, and sliding along DNA
      provides for the faster one-dimensional search. Surprisingly, the role of DNA
      conformation was never considered in this context. In this article, we explicitly
      address the relative role of three-dimensional diffusion and one-dimensional
      sliding along coiled or globular DNA and the possibility of correlated
      readsorption of desorbed proteins. We have identified a wealth of new different
      scaling regimes. We also found the maximal possible acceleration of the reaction
      due to sliding. We found that the maximum on the rate-versus-ionic strength curve
      is asymmetric, and that sliding can lead not only to acceleration, but also in
      some regimes to dramatic deceleration of the reaction.

PMID- 16461403
TI  - A protein dynamics study of photosystem II: the effects of protein conformation
      on reaction center function.
AB  - Molecular dynamics simulations have been performed to study photosystem II
      structure and function. Structural information obtained from simulations was
      combined with ab initio computations of chromophore excited states. In contrast
      to calculations based on the x-ray structure, the molecular-dynamics-based
      calculations accurately predicted the experimental absorbance spectrum. In
      addition, our calculations correctly assigned the energy levels of reaction
      center (RC) chromophores, as well as the lowest-energy antenna chlorophyll. The
      primary and secondary quinone electron acceptors, Q(A) and Q(B), exhibited
      independent changes in position over the duration of the simulation. Q(B)
      fluctuated between two binding sites similar to the proximal and distal sites
      previously observed in light- and dark-adapted RC from purple bacteria. Kinetic
      models were used to characterize the relative influence of chromophore geometry,
      site energies, and electron transport rates on RC efficiency. The fluctuating
      energy levels of antenna chromophores had a larger impact on quantum yield than
      did their relative positions. Variations in electron transport rates had the most
      significant effect and were sufficient to explain the experimentally observed
      multi-component decay of excitation in photosystem II. The implications of our
      results are discussed in the context of competing evolutionary selection
      pressures for RC structure and function.

PMID- 16461405
TI  - Structural transitions of confined model proteins: molecular dynamics simulation
      and experimental validation.
AB  - Proteins fold in a confined space not only in vivo, i.e., folding assisted by
      molecular chaperons and chaperonins in a crowded cellular medium, but also in
      vitro as in production of recombinant proteins. Despite extensive work on protein
      folding in bulk, little is known about how and to what extent the thermodynamics
      and kinetics of protein folding are altered by confinement. In this work, we use
      a Go-like off-lattice model to investigate the folding and stability of an all
      beta-sheet protein in spherical cages of different sizes and surface
      hydrophobicity. We find whereas extreme confinement inhibits correct folding, a
      hydrophilic cage stabilizes the protein due to restriction of the unfolded
      configurations. In a hydrophobic cage, however, strong attraction from the cage
      surface destabilizes the confined protein because of competition between self
      aggregation and adsorption of hydrophobic residues. We show that the kinetics of
      protein collapse and folding is strongly correlated with both the cage size and
      the surface hydrophobicity. It is demonstrated that a cage of moderate size and
      hydrophobicity optimizes both the folding yield and kinetics of structural
      transitions. To support the simulation results, we have also investigated the
      refolding of hen-egg lysozyme in the presence of cetyltrimethylammoniumbromide
      (CTAB) surfactants that provide an effective confinement of the proteins by
      micellization. The influence of the surfactant hydrophobicity on the structural
      and biological activity of the protein is determined with circular dichroism
      spectrum, fluorescence emission spectrum, and biological activity assay. It is
      shown that, as predicted by coarse-grained simulations, CTAB micelles facilitate
      the collapse of denatured lysozyme, whereas the addition of beta-cyclodextrin
      grafted-PNIPAAm, a weakly hydrophobic stripper, dissociates CTAB micelles and
      promotes the conformational rearrangement and thereby gives an improved recovery
      of lysozyme activity.

PMID- 16461404
TI  - Statistical evaluation of ion-channel gating models based on distributions of log
      likelihood ratios.
AB  - The distributions of log-likelihood ratios (DeltaLL) obtained from fitting ion
      channel dwell-time distributions with nested pairs of gating models (Xi, full
      model; Xi(R), submodel) were studied both theoretically and using simulated data.
      When Xi is true, DeltaLL is asymptotically normally distributed with predictable
      mean and variance that increase linearly with data length (n). When Xi(R) is true
      and corresponds to a distinct point in full parameter space, DeltaLL is Gamma
      distributed (2DeltaLL is chi-square). However, when data generated by an l
      component multiexponential distribution are fitted by l+1 components, Xi(R)
      corresponds to an infinite set of points in parameter space. The distribution of
      DeltaLL is a mixture of two components, one identically zero, the other
      approximated by a Gamma-distribution. This empirical distribution of DeltaLL,
      assuming Xi(R), allows construction of a valid log-likelihood ratio test. The log
      likelihood ratio test, the Akaike information criterion, and the Schwarz
      criterion all produce asymmetrical Type I and II errors and inefficiently
      recognize Xi, when true, from short datasets. A new decision strategy, which
      considers both the parameter estimates and DeltaLL, yields more symmetrical
      errors and a larger discrimination power for small n. These observations are
      explained by the distributions of DeltaLL when Xi or Xi(R) is true.

PMID- 16461406
TI  - Aligning Paramecium caudatum with static magnetic fields.
AB  - As they negotiate their environs, unicellular organisms adjust their swimming in
      response to various physical fields such as temperature, chemical gradients, and
      electric fields. Because of the weak magnetic properties of most biological
      materials, however, they do not respond to the earth's magnetic field (5 x 10(-5)
      Tesla) except in rare cases. Here, we show that the trajectories of Paramecium
      caudatum align with intense static magnetic fields >3 Tesla. Otherwise straight
      trajectories curve in magnetic fields and eventually orient parallel or
      antiparallel to the applied field direction. Neutrally buoyant immobilized
      paramecia also align with their long axis in the direction of the field. We model
      this magneto-orientation as a strictly passive, nonphysiological response to a
      magnetic torque exerted on the diamagnetically anisotropic components of the
      paramecia. We have determined the average net anisotropy of the diamagnetic
      susceptibility, Deltachi(p), of a whole Paramecium: Deltachi(p) = (6.7+/- 0.7) x
      10(-23) m(3). We show how the measured Deltachi(p) compares to the anisotropy of
      the diamagnetic susceptibilities of the components in the cell. We suggest that
      magnetic fields can be exploited as a novel, noninvasive, quantitative means to
      manipulate swimming populations of unicellular organisms.

PMID- 16461408
TI  - Systematic analysis of conservation relations in Escherichia coli genome-scale
      metabolic network reveals novel growth media.
AB  - A biochemical species is called producible in a constraints-based metabolic model
      if a feasible steady-state flux configuration exists that sustains its nonzero
      concentration during growth. Extreme semipositive conservation relations (ESCRs)
      are the simplest semipositive linear combinations of species concentrations that
      are invariant to all metabolic flux configurations. In this article, we outline a
      fundamental relationship between the ESCRs of a metabolic network and the
      producibility of a biochemical species under a nutrient media. We exploit this
      relationship in an algorithm that systematically enumerates all minimal nutrient
      sets that render an objective species weakly producible (i.e., producible in the
      absence of thermodynamic constraints) through a simple traversal of ESCRs. We
      apply our results to a recent genome scale model of Escherichia coli metabolism,
      in which we traverse the 51 anhydrous ESCRs of the metabolic network to determine
      all 928 minimal aqueous nutrient media that render biomass weakly producible.
      Applying irreversibility constraints, we find 287 of these 928 nutrient sets to
      be thermodynamically feasible. We also find that an additional 365 of these
      nutrient sets are thermodynamically feasible in the presence of oxygen. Since
      biomass producibility is commonly used as a surrogate for growth in genome scale
      metabolic models, our results represent testable hypotheses of alternate growth
      media derived from in silico analysis of the E. coli genome scale metabolic
      network.

PMID- 16461407
TI  - Domain-induced activation of human phospholipase A2 type IIA: local versus global
      lipid composition.
AB  - Secretory human phospholipase A2 type IIA (PLA2-IIA) catalyzes the hydrolysis of
      the sn-2 ester bond in glycerolipids to produce fatty acids and lysolipids. The
      enzyme is coupled to the inflammatory response, and its specificity toward
      anionic membrane interfaces suggests a role as a bactericidal agent. PLA2-IIA may
      also target perturbed native cell membranes that expose anionic lipids to the
      extracellular face. However, anionic lipid contents in native cells appear lower
      than the threshold levels necessary for activation. By using
      phosphatidylcholine/phosphatidylglycerol model systems, we show that local
      enrichment of anionic lipids into fluid domains triggers PLA2-IIA activity. In
      addition, the compositional range of enzyme activity is shown to be related to
      the underlying lipid phase diagram. A comparison is done between PLA2-IIA and
      snake venom PLA2, which in contrast to PLA2-IIA hydrolyzes both anionic and
      zwitterionic membranes. In general, this work shows that PLA2-IIA activation can
      be accomplished through local enrichment of anionic lipids into domains,
      indicating a mechanism for PLA2-IIA to target perturbed native membranes with low
      global anionic lipid contents. The results also show that the underlying lipid
      phase diagram, which determines the lipid composition at a local level, can be
      used to predict PLA2-IIA activity.

PMID- 16461409
TI  - Building safer environments: injury, safety, and our surroundings.

PMID- 16461410
TI  - Governmental health agencies need to assume leadership in injury prevention.

PMID- 16461411
TI  - Sports utility vehicles and older pedestrians: a damaging collision.

PMID- 16461412
TI  - Wheelchair related injuries treated in US emergency departments.
AB  - OBJECTIVE: To characterize the trend of wheelchair related injuries over time,
      and describe the demographics and characteristics of wheelchair users' injuries
      by age group. METHODS: Data from the National Electronic Injury Surveillance
      System (NEISS) were analyzed. RESULTS: In 2003, more than 100,000 wheelchair
      related injuries were treated in emergency departments in the US, double the
      number reported in 1991. Tips and falls accounted for 65-80% of injuries across
      all age groups of wheelchair users. The majority of children's injuries occurred
      at locations outside of homes and institutions/hospitals in environments with
      stairs, ramps, and curbs (57.3%). In contrast, injuries among adult users were
      more likely to occur in homes, hospitals, and institutions (45-90%). CONCLUSIONS:
      Wheelchair related injuries may have increased in the US during the past decade.
      Prevention efforts should address the interacting complex factors that influence
      risk of injury while using a wheelchair.

PMID- 16461413
TI  - Emergency presentations by vulnerable road users: implications for injury
      prevention.
AB  - Most emergency presentations by vulnerable road users were the result of
      collisions that did not involve a motor vehicle. Many injuries occurred off-road
      without police attendance. Hence, reliance on official police records would
      underestimate the magnitude and scope of these injuries. Suggestions to provide a
      safer road environment are given.

PMID- 16461414
TI  - Violence in Jamaica: an analysis of homicides 1998-2002.
AB  - The aim of the study was to create a profile of Jamaican homicide victims and to
      describe the circumstances, motives, and the weapons used in homicide incidents.
      The authors read the police narratives for all Jamaican homicides 1998-2002 and
      coded them using a predetermined set of variables. Analyses were conducted to
      describe victim characteristics, motive, and weapon use. The majority of homicide
      victims were male (over 89%), and 15-44 years old (80%). The rate of homicide for
      males age 15-44 years was 121 per 100,000 compared with a rate of 12 per 100,000
      for females in the same age group. The main motives for homicide were disputes
      (29%) and reprisals (30%). Gunshot wounds were the cause of death in 66% of all
      homicides. Guns were used primarily in reprisals, robbery, and drug/gang related
      homicides; in half of all dispute related homicides the perpetrator used a knife.
      Homicides in Jamaica are not primarily gang or robbery related. Rather, they are
      mainly caused by arguments or reprisals. Homicide has become a common feature of
      dispute resolution in Jamaica.

PMID- 16461415
TI  - The Parent Supervision Attributes Profile Questionnaire: a measure of supervision
      relevant to children's risk of unintentional injury.
AB  - OBJECTIVE: To further establish the psychometric properties of the Parent
      Supervision Attributes Profile Questionnaire (PSAPQ), a questionnaire measure of
      parent supervision that is relevant to understanding risk of unintentional injury
      among children 2 through 5 years of age. METHODS: To assess test-retest
      reliability, parents completed the PSAPQ twice, with a one month interval.
      Internal consistency estimates for the PSAPQ were also computed. Confirmatory
      factor analyses were applied to the data to assess the four factor structure of
      the instrument by assessing the convergent and divergent validity of the
      subscales and their respective items. RESULTS: Test-retest reliability and
      internal consistency scores were good, exceeding 0.70 for all subscales. Factor
      analyses confirmed the hypothesized model--namely that the 29 item questionnaire
      comprised four unique factors: protectiveness, supervision beliefs, risk
      tolerance, and fate influences on child safety. CONCLUSIONS: Previous tests
      comparing the PSAPQ with indices of actual supervision and children's injury
      history scores revealed good criterion validity. The present assessment of the
      PSAPQ revealed good reliability (test-retest reliability, internal consistency)
      and established the convergent and divergent validity of the four factors. Thus,
      the PSAPQ has proven to have strong psychometric properties, making it a unique
      and useful measure for researchers interested in studying links between
      supervision and young children's risks of unintentional injury.

PMID- 16461416
TI  - The ICD-10 injury mortality diagnosis matrix.
AB  - OBJECTIVE: To standardize the presentation of the more than 1200 ICD-10 "S" and
      "T" codes from Chapter XIX by cross classifying the body region of injury by the
      nature of injury using the ICD-10 injury mortality diagnosis matrix. This paper
      explains the rationale for decisions made when developing the matrix and presents
      mortality data using the matrix. DESIGN: ICD-10 codes are organized by diagnosis
      groups and body regions of injury for the purpose of standardizing presentation.
      The categories can be collapsed to facilitate analysis at varying levels of
      detail. Findings from the United States 2002 injury mortality data are used as an
      example. MAIN OUTCOME MEASURES: All injury diagnoses mentioned in deaths with an
      underlying cause of injury. RESULTS: There were a total of 247,195 injury
      diagnoses mentioned in the 161,269 deaths with an underlying cause of injury in
      2002 in the United States. The matrix can be used to show that 30% of all injury
      diagnoses mentioned were to the head and neck region; 28% were system wide
      injuries, 17% were to the torso. Open wounds accounted for 17% of all injury
      diagnoses mentioned, and close to half of all open wounds were traumatic brain
      injuries. Twenty eight percent of injury diagnoses mentioned were unspecified as
      to their nature and 9.5% had no body region specified. CONCLUSIONS: Multiple
      cause of death data are a rich but underused source of injury data often due to
      the complexity of the data and of the ICD classification system. Analytic
      techniques will need to be refined to accommodate deaths with multiple
      contributing injury diagnoses. The injury mortality diagnosis matrix will
      facilitate analysis as it is a useful tool for summarizing diagnosis data
      associated with injury deaths.

PMID- 16461417
TI  - ATVs: motorized toys or vehicles for children?
AB  - OBJECTIVES: To compare the nature of injuries from all-terrain vehicles (ATVs) to
      those from bicycling, dirtbikes/motocross, and motor vehicle crashes. DESIGN:
      Data on injuries from the mechanisms outlined above were obtained through CHIRPP
      (the Canadian Hospitals Injury Reporting and Prevention Program) and hospital
      records. SETTING: A Canadian tertiary pediatric center. SUBJECTS: Cases
      presenting to the emergency department over a 10 year period. MAIN OUTCOME
      MEASURES: Comparison between demographics, mechanisms and natures of injuries
      sustained, disposition from the emergency department, and lengths of hospital
      stay. RESULTS: Contrary to bicycling, ATV related injuries occurred among older
      ages and appeared to result less often from loss of control. Severe injuries
      resulting in deep soft tissue trauma and fracture/dislocations were 1.7 and 1.5
      times, respectively, more frequent among ATV trauma than bicycling (p<0.01). In
      addition, ATV related injuries were located more frequently in the trunkal, hip,
      lower extremity, and spinal regions. Conversely, ATV related trauma bore
      significant similarities regarding body part and nature of the injury to both
      motor vehicle crash (MVC) and dirtbike related injuries. Akin to dirtbike and MVC
      related trauma, ATV related injuries more frequently required admission to the
      ward or intensive care unit compared to bicycling injuries (30.8% v 9.6%,
      p<0.0001), and used a proportionally larger amount of hospital resources with
      respect to overall in-hospital and intensive care unit days. CONCLUSIONS:
      Although ATVs may be considered recreational for children, their associated
      injury patterns, severity, and costs to the healthcare system more closely
      resemble those from motorized vehicles and are more significant than bicycling.
      Strict policy to reflect this must be developed and acknowledged by the public,
      industry, and legislative bodies.

PMID- 16461418
TI  - Differential strength of association of child injury prevention attitudes and
      beliefs on practices: a case for audience segmentation.
AB  - OBJECTIVE: Many injuries to children cannot be prevented without some degree of
      active behavior on the part of parents. A better understanding of social and
      cognitive determinants of parents' injury prevention behavior and the
      identification of potential subgroups for targeted message delivery could advance
      the effectiveness of educational and behavioral interventions. This study
      assessed the degree to which parents' injury prevention behavior is associated
      with theoretical determinants and examined whether this relation differs by age
      or birth order of child. DESIGN: Cross sectional observational study. SETTING:
      Three Midwestern pediatric clinics. SUBJECTS: 594 parents of children ages 0-4
      attending routine well child visits. MEASURES: Injury prevention attitudes,
      beliefs, and practices. RESULTS: Overall, only modest relations were observed
      between injury beliefs and attitudes and injury prevention behaviors. However,
      these relations differed substantially by child age and birth order, with
      stronger associations observed for parents of older first born children. Outcome
      expectations and social norms were more strongly related to injury prevention
      behavior among parents of preschool children than among parents of infants and
      toddlers, while attitudes were more predictive for parents of first born children
      than parents of later born children. CONCLUSIONS: These findings highlight the
      complexity of relations between theorized determinants and behavior, and suggest
      the potential utility of using audience segmentation strategies in behavioral
      interventions addressing injury prevention.

PMID- 16461419
TI  - Firearm suicide in New York City in the 1990s.
AB  - OBJECTIVE: Across the US, firearms are used in approximately 60% of all suicide
      deaths. Little research has assessed the role and determinants of firearms in
      suicide in major urban areas. METHODS: The authors collected data on all suicide
      deaths between 1990 and 2000 from the Office of the Chief Medical Examiner of New
      York City (NYC) and assessed trends and correlates of firearm related suicide
      deaths. RESULTS: During the period studied, there were a total of 6008 suicides
      in NYC; 1200 (20.0%) were firearm related suicides. There was a decrease in total
      suicides, total firearm suicides, and the proportion of firearm related suicides.
      In multivariable modeling, characteristics of suicide decedents associated with a
      greater likelihood of firearm suicide were: male, black race, residing in the
      outer boroughs, and use of cannabis. CONCLUSIONS: The proportion of suicides
      caused by firearms in NYC is low compared to other parts of the US; differential
      access to means of committing suicide and the differential importance of firearms
      in different racial and ethnic groups may contribute to this observation.
      Innovative, local population based interventions that target non-firearm related
      suicide may contribute to lower suicide mortality overall in urban areas.

PMID- 16461420
TI  - Validating self reported home safety practices in a culturally diverse non-inner
      city population.
AB  - OBJECTIVE: To determine the validity of face to face, self reported responses to
      questions about the presence of safety devices and use of safety practices in the
      home aimed at preventing unintended injuries to preschool aged children. METHODS:
      The authors invited families with children enrolling in a medium sized Midwestern
      US community Head Start program to participate in a randomized study of home
      safety practices. Participation involved consenting parents (n = 452) completing
      an initial questionnaire during Head Start enrollment or in their home. Project
      staff conducted home inspections to confirm parental responses to 16 questions.
      Only inspections conducted within 34 days of questionnaire completion (n = 259)
      were included in the validation study. Parents were told that the home visit
      would assess the need for safety devices, but were not informed of the validation
      aspect of the study. RESULTS: Sensitivities were generally high for all 16 safety
      practices, whereas negative predictive value and specificity varied considerably.
      Positive predictive value was also high for most practices, and did not vary by
      ethnicity. Answers provided by parents in their home were different and more
      reliable than those provided by parents interviewed at school (p = 0.001).
      CONCLUSIONS: Use of safety devices and practices by parents of preschool aged
      children reported in a face to face interview are generally reliable. Reliability
      increases if the interview is conducted in the home. Parents may also be more
      willing to report potential problems if they perceive they may receive corrective
      assistance.

PMID- 16461421
TI  - Accuracy of injury coding under ICD-9 for New Zealand public hospital discharges.
AB  - OBJECTIVE: To determine the level of accuracy in coding for injury principal
      diagnosis and the first external cause code for public hospital discharges in New
      Zealand and determine how these levels vary by hospital size. METHOD: A simple
      random sample of 1800 discharges was selected from the period 1996-98 inclusive.
      Records were obtained from hospitals and an accredited coder coded the discharge
      independently of the codes already recorded in the national database. RESULTS:
      Five percent of the principal diagnoses, 18% of the first four digits of the E
      codes, and 8% of the location codes (5th digit of the E-code), were incorrect.
      There were no substantive differences in the level of incorrect coding between
      large and small hospitals. CONCLUSIONS: Users of New Zealand public hospital
      discharge data can have a high degree of confidence in the injury diagnoses coded
      under ICD-9-CM-A. A similar degree of confidence is warranted for E-coding at the
      group level (for example, fall), but not, in general, at higher levels of
      specificity (for example, type of fall). For those countries continuing to use
      ICD-9 the study provides insight into potential problems of coding and thus
      guidance on where the focus of coder training should be placed. For those
      countries that have historical data coded according to ICD-9 it suggests that
      some specific injury and external cause incidence estimates may need to be
      treated with more caution.

PMID- 16461422
TI  - Global Campaign for Violence Prevention: significant progress for many countries.

PMID- 16461424
TI  - Using plasma topotecan pharmacokinetics to estimate topotecan exposure in
      cerebrospinal fluid of children with medulloblastoma.
AB  - The purpose of this study was to estimate ventricular cerebrospinal fluid (vCSF)
      topotecan lactone (TPT) exposures in pediatric medulloblastoma patients from
      plasma concentration-time data by using a pharmacokinetic (PK) model. We studied
      children with high-risk medulloblastoma who received pharmacokinetically guided
      TPT (target plasma area under the concentration-time curve [AUC], 120-160 ng/ml
      h) and obtained serial vCSF samples to assess TPT exposure. Population
      pharmacokinetic parameters were determined by using linear mixed-effects modeling
      via the two-stage approach. We simulated TPT vCSF exposure duration at plasma TPT
      AUC values of 120 to 200 ng/ml-h and determined percentages of studies meeting or
      exceeding the vCSF exposure duration threshold (EDT) of 1 ng/ml for 8 h. We then
      used bootstrap methods to estimate variability in vCSF EDT. Eighteen PK studies
      were conducted in six patients (median age, 4.8 years). In these patients, seven
      of nine studies attaining target plasma TPT AUC achieved the vCSF EDT. Given a
      plasma TPT AUC of 120 ng/ml-h, the median percentage of results meeting or
      exceeding EDT was 78% (95% CI, 61%-100%). One patient (four studies) with tumor
      blockage of CSF flow, which can alter CSF pharmacokinetics, was removed, and the
      bootstrap analysis was repeated. In this subset, a median 93% (95% CI, 79%-100%)
      of studies achieved vCSF EDT. Increasing plasma TPT AUC values resulted in
      increased ability to achieve vCSF EDT. We demonstrated that a plasma PK model
      could estimate vCSF TPT concentrations. Further, our results indicate that the
      TPT vCSF EDT can be achieved in more than 80% of studies targeted to a plasma TPT
      AUC of 120 ng/ml-h.

PMID- 16461425
TI  - Evolution of the bipolar mating system of the mushroom Coprinellus disseminatus
      from its tetrapolar ancestors involves loss of mating-type-specific pheromone
      receptor function.
AB  - Mating incompatibility in mushroom fungi is controlled by the mating-type loci.
      In tetrapolar species, two unlinked mating-type loci exist (A and B), whereas in
      bipolar species there is only one locus. The A and B mating-type loci encode
      homeodomain transcription factors and pheromones and pheromone receptors,
      respectively. Most mushroom species have a tetrapolar mating system, but numerous
      transitions to bipolar mating systems have occurred. Here we determined the genes
      controlling mating type in the bipolar mushroom Coprinellus disseminatus. Through
      positional cloning and degenerate PCR, we sequenced both the transcription factor
      and pheromone receptor mating-type gene homologs from C. disseminatus. Only the
      transcription factor genes segregate with mating type, discounting the hypothesis
      of genetic linkage between the A and B mating-type loci as the causal origin of
      bipolar mating behavior. The mating-type locus of C. disseminatus is similar to
      the A mating-type locus of the model species Coprinopsis cinerea and encodes two
      tightly linked pairs of homeodomain transcription factor genes. When transformed
      into C. cinerea, the C. disseminatus A and B homologs elicited sexual reactions
      like native mating-type genes. Although mating type in C. disseminatus is
      controlled by only the transcription factor genes, cellular functions appear to
      be conserved for both groups of genes.

PMID- 16461426
TI  - Lysophosphatidylcholine impairs endothelial barrier function through the G
      protein-coupled receptor GPR4.
AB  - Abundant evidence indicates that lysophosphatidylcholine (LPC) is proinflammatory
      and atherogenic. In the vascular endothelium, LPC increases permeability and
      expression of proinflammatory molecules such as adhesion molecules and cytokines.
      Yet, mechanisms by which LPC mediates these activities remain unclear and
      controversial. Recent evidence implicates involvement of a novel subfamily of G
      protein-coupled receptors (GPR4, G2A, OGR1, and TDAG8) that are sensitive to
      lysolipids and protons. We previously reported that one of these receptors, GPR4,
      is selectively expressed by a variety of endothelial cells and therefore
      hypothesize that the LPC-stimulated endothelial barrier dysfunction is mediated
      through GPR4. We developed a peptide Ab against GPR4 that detected GPR4
      expression in transfected COS 7 cells and endogenous GPR4 expression in
      endothelial cells by Western blot. Endothelial cells infected with a retrovirus
      containing small interference RNA (siRNA) to GPR4 resulted in 40-50% decreased
      GPR4 expression, which corresponded with partial prevention of the LPC-induced 1)
      decrease in transendothelial resistance, 2) stress fiber formation, and 3)
      activation of RhoA. Furthermore, coexpression of the siRNA-GPR4 with a siRNA
      resistant mutant GPR4 fully restored the LPC-induced resistance decrease.
      However, extracellular pH of <7.4 did not alter baseline or LPC-stimulated
      resistances. The results provide strong evidence that the LPC-mediated
      endothelial barrier dysfunction is regulated by endogenous GPR4 in endothelial
      cells and suggest that GPR4 may play a critical role in the inflammatory
      responses activated by LPC.

PMID- 16461427
TI  - Modulation of the Ca2+ sensitivity of airway smooth muscle cells in murine lung
      slices.
AB  - To investigate the phenomenon of Ca(2+) sensitization, we developed a new intact
      airway and arteriole smooth muscle cell (SMC) "model" by treating murine lung
      slices with ryanodine-receptor antagonist, ryanodine (50 microM), and caffeine
      (20 mM). A sustained elevation in intracellular Ca(2+) concentration
      ([Ca(2+)](i)) was induced in both SMC types by the ryanodine-caffeine treatment
      due to the depletion of internal Ca(2+) stores and the stimulation of a
      persistent influx of Ca(2+). Arterioles responded to this sustained increase in
      [Ca(2+)](i) with a sustained contraction. By contrast, airways responded to
      sustained high [Ca(2+)](i) with a transient contraction followed by relaxation.
      Subsequent exposure to methacholine (MCh) induced a sustained concentration
      dependent contraction of the airway without a change in the [Ca(2+)](i). During
      sustained MCh-induced contraction, Y-27632 (a Rho-kinase inhibitor) and GF
      109203X (a protein kinase C inhibitor) induced a concentration-dependent
      relaxation without changing the [Ca(2+)](i). The cAMP-elevating agents, forskolin
      (an adenylyl cyclase activator), IBMX (a phosphodiesterase inhibitor), and
      caffeine (also acting as a phosphodiesterase inhibitor), exerted similar relaxing
      effects. These results indicate that 1) ryanodine-caffeine treatment is a
      valuable tool for investigating the contractile mechanisms of SMCs while avoiding
      nonspecific effects due to cell permeabilization, 2) in the absence of agonist,
      sustained high [Ca(2+)](i) has a differential time-dependent effect on the Ca(2+)
      sensitivity of airway and arteriole SMCs, 3) MCh facilitates the contraction of
      airway SMCs by inducing Ca(2+) sensitization via the activation of Rho-kinase and
      protein kinase C, and 4) cAMP-elevating agents contribute to the relaxation of
      airway SMCs through Ca(2+) desensitization.

PMID- 16461428
TI  - Nerve growth factor-enhanced airway responsiveness involves substance P in ferret
      intrinsic airway neurons.
AB  - Nerve growth factor (NGF), a member of the neurotrophin family, enhances
      synthesis of neuropeptides in sensory and sympathetic neurons. The aim of this
      study was to examine the effect of NGF on airway responsiveness and determine
      whether these effects are mediated through synthesis and release of substance P
      (SP) from the intrinsic airway neurons. Ferrets were instilled intratracheally
      with NGF or saline. Tracheal smooth muscle contractility to methacholine and
      electrical field stimulation (EFS) was assessed in vitro. Contractions of
      isolated tracheal smooth muscle to EFS at 10 and 30 Hz were significantly
      increased in the NGF treatment group (10 Hz: 33.57 +/- 2.44%; 30 Hz: 40.12 +/-
      2.78%) compared with the control group (10 Hz: 27.24 +/- 2.14%; 30 Hz: 33.33 +/-
      2.31%). However, constrictive response to cholinergic agonist was not
      significantly altered between the NGF treatment group and the control group. The
      NGF-induced modulation of airway smooth muscle to EFS was maintained in tracheal
      segments cultured for 24 h, a procedure that causes a significant anatomic and
      functional loss of SP-containing sensory fibers while maintaining viability of
      intrinsic airway neurons. The number of SP-containing neurons in longitudinal
      trunk and superficial muscular plexus and SP nerve fiber density in tracheal
      smooth muscle all increased significantly in cultured trachea treated with NGF.
      Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated
      the NGF-induced increased contraction to EFS in cultured segments but had no
      effect in saline controls. These results show that the NGF-enhanced airway smooth
      muscle contractile responses to EFS are mediated by the actions of SP released
      from intrinsic airway neurons.

PMID- 16461429
TI  - Ablation of the complement C3a anaphylatoxin receptor causes enhanced killing of
      Pseudomonas aeruginosa in a mouse model of pneumonia.
AB  - The C3a anaphylatoxin is a 77-amino acid peptide that is generated by enzymatic
      cleavage of C3 during activation of the complement system. C3a mediates numerous
      biological functions on binding its receptor (C3aR), which is present on both
      myeloid and nonmyeloid cells. To investigate the biological impact of C3a
      mediated effects during acute pneumonia caused by Pseudomonas aeruginosa, we
      subjected C3aR-deficient mice and matched wild-type (WT) mice to P. aeruginosa
      pulmonary infection. C3aR-deficient mice exhibited increased killing of P.
      aeruginosa in the lungs, less dissemination of bacteria into the bloodstream, and
      a decreased inflammatory response to P. aeruginosa pulmonary infection compared
      with WT mice. To examine whether the absence of C3aR would impact the humoral
      immune response to P. aeruginosa, we immunized WT and C3aR-deficient mice via
      intraperitoneal injection with live P. aeruginosa. Both groups of mice developed
      similar levels of antibody specific to P. aeruginosa. Immunized C3aR-deficient
      and WT mice were subjected to P. aeruginosa pulmonary infection, and C3aR
      deficient mice again displayed increased killing of P. aeruginosa in the lungs,
      less dissemination of bacteria into the bloodstream, and a decreased inflammatory
      response in the lungs. Collectively, these data demonstrate that independently of
      antibody production, absence of C3aR causes enhanced killing of P. aeruginosa
      despite a diminished inflammatory response in a mouse model of pneumonia.

PMID- 16461430
TI  - Age-specific pulmonary cytochrome P-450 3A1 expression in postnatal and adult
      rats.
AB  - A major cause of death and illness in children under the age of five, most living
      in polluted cities, is respiratory disease. Previous studies have shown that
      neonatal animals are more susceptible to bioactivated pulmonary cytotoxicants
      than adults, despite lower expression of the pulmonary cytochrome P-450s
      (CYP450s) thought to be involved in bioactivation. One CYP450 that is well
      documented in the bioactivation of many drugs and environmental toxicants in
      adult lung, but whose expression has not been evaluated during postnatal
      pulmonary development, is CYP450 3A (CYP3A). We compared age-specific expression
      of CYP3A1 in 7-day-old and adult male Sprague-Dawley rats. Unlike those shown for
      previously studied pulmonary CYP450s, expression levels for CYP3A1 mRNA in
      differentiating airway cells of postnatal rats are the same as in fully
      differentiated airway cells of adults. CYP3A1 protein expression (28%) and
      enzymatic activity (23%) were lower in postnatal airways compared with adults.
      Although other CYP450 immunoreactive proteins are primarily expressed in
      nonciliated cells, immunoreactive CYP3A1 protein was expressed in both ciliated
      and nonciliated cells in postnatal and adult rat proximal airways. CYP3A1 protein
      is detected diffusely throughout ciliated and nonciliated cells in 7-day-old
      rats, whereas it is only detected in the apex of these cells in adult rats. This
      study demonstrates that the lungs of postnatal rats have detectable levels of
      CYP3A1 and that CYP3A1 mRNA expression appears not to be age dependent, whereas
      steady-state CYP3A1 protein levels and enzyme activity show an age-dependent
      pattern.

PMID- 16461431
TI  - ICAM-1 and LFA-1 play critical roles in LPS-induced neutrophil recruitment into
      the alveolar space.
AB  - Neutrophil recruitment into lung constitutes a major response to airborne
      endotoxins. In many tissues endothelial intercellular adhesion molecule-1 (ICAM
      1) interacts with lymphocyte function associated antigen-1 (LFA-1) on
      neutrophils, and this interaction plays a critical role in neutrophil
      recruitment. There are conflicting reports about the role of ICAM-1 in neutrophil
      recruitment into lungs. We studied neutrophil recruitment into alveolar space in
      a murine model of aerosolized LPS-induced lung inflammation. LPS induces at least
      a 100-fold increase in neutrophil numbers in alveolar space, as determined by
      flow cytometry of bronchoalveolar lavage fluid. Neutrophil recruitment was
      reduced by 54% in ICAM-1 null mice and by 45% in LFA-1 null mice. In wild-type
      mice treated with anti-ICAM-1 and anti-LFA-1 antibodies, there was 51 and 58%
      reduction in the neutrophil recruitment, respectively. In chimeric mice,
      generated by the transplantation of mixtures of bone marrows from LFA-1 null and
      wild-type mice, the normalized recruitment of LFA-1 null neutrophils was reduced
      by 60% compared with wild-type neutrophils. Neither the treatment of ICAM-1 null
      mice with a function-blocking antibody to LFA-1 nor the treatment of LFA-1 null
      mice with anti-ICAM-1 antibody resulted in further reduction in the recruitment
      compared with untreated ICAM-1 null and LFA-1 null mice. We conclude that ICAM-1
      and LFA-1 play critical roles in the recruitment of neutrophils into the alveolar
      space in aerosolized LPS-induced lung inflammation, and LFA-1 serves as a ligand
      of ICAM-1 in the lung.

PMID- 16461432
TI  - Hypoxia upregulates lung microvascular neurokinin-1 receptor expression.
AB  - Subacute exposure to moderate hypoxia can promote pulmonary edema formation. The
      tachykinins, a family of proinflammatory neuropeptides, have been implicated in
      the pathogenesis of pulmonary edema in some settings, including the pulmonary
      vascular leak associated with exposure to hypoxia. The effects of hypoxia on
      tachykinin receptor and peptide expression in the lung, however, remain poorly
      understood. We hypothesized that subacute exposure to moderate hypoxia increases
      lung neurokinin-1 (NK-1) receptor expression as well as lung substance P levels.
      We tested this hypothesis by exposing weanling Sprague-Dawley rats to hypobaric
      hypoxia (barometric pressure 0.5 atm) for 0, 24, 48, or 72 h. Hypoxia led to time
      dependent increases in lung NK-1 receptor mRNA expression and lung NK-1 receptor
      protein levels at 48 and 72 h of exposure (P < 0.05). Immunohistochemistry and in
      situ NK-1 receptor labeling with substance P-conjugated fluorescent nanocrystals
      demonstrated that hypoxia increased NK-1 expression primarily in the pulmonary
      microvasculature and in alveolar macrophages. Hypoxia also led to increases in
      lung substance P levels by 48 and 72 h (P < 0.05) but led to a decrease in
      preprotachykinin mRNA levels (P < 0.05). We conclude that subacute exposure to
      moderate hypoxia upregulates lung NK-1 receptor expression and lung substance P
      peptide levels primarily in the lung microvasculature. We speculate that this
      effect may contribute to the formation of pulmonary edema in the setting of
      regional or environmental hypoxia.

PMID- 16461433
TI  - Cyclic stretch attenuates effects of hyperoxia on cell proliferation and
      viability in human alveolar epithelial cells.
AB  - The treatment of severe lung disease often requires the use of high
      concentrations of oxygen coupled with the need for assisted ventilation,
      potentially exposing the pulmonary epithelium to both reactive oxygen species and
      nonphysiological cyclic stretch. Whereas prolonged hyperoxia is known to cause
      increased cell injury, cyclic stretch may result in either cell proliferation or
      injury depending on the pattern and degree of exposure to mechanical deformation.
      How hyperoxia and cyclic stretch interact to affect the pulmonary epithelium in
      vitro has not been previously investigated. This study was performed using human
      alveolar epithelial A549 cells to explore the combined effects of cyclic stretch
      and hyperoxia on cell proliferation and viability. Under room air conditions,
      cyclic stretch did not alter cell viability at any time point and increased cell
      number after 48 h compared with unstretched controls. After exposure to prolonged
      hyperoxia, cell number and [(3)H]thymidine incorporation markedly decreased,
      whereas evidence of oxidative stress and nonapoptotic cell death increased. The
      combination of cyclic stretch with hyperoxia significantly mitigated the negative
      effects of prolonged hyperoxia alone on measures of cell proliferation and
      viability. In addition, cyclic stretch resulted in decreased levels of oxidative
      stress over time in hyperoxia-exposed cells. Our results suggest that cyclic
      stretch, as applied in this study, can minimize the detrimental effects of
      hyperoxia on alveolar epithelial A549 cells.

PMID- 16461434
TI  - Re: Sensory-motor incongruence and reports of 'pain', by G. L. Moseley and S. C.
      Gandevia. Rheumatology 2005;44:1083-1085.

PMID- 16461435
TI  - Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis.
AB  - OBJECTIVE: To describe the efficacy of anti-TNF-alpha agents in the treatment of
      childhood uveitis. METHODS: We performed a retrospective chart review of all
      children with uveitis treated with TNF-alpha blockers at The Hospital for Sick
      Children, Toronto. RESULTS: Twenty-one children with uveitis were treated with
      the anti-TNF-alpha agents etanercept (11 patients) and infliximab (13 patients),
      resulting in 24 treatment courses. All patients had persistently active uveitis
      despite treatment with at least one standard immunosuppressive drug before the
      start of anti-TNF-alpha therapy. Six of 21 patients (29%) had idiopathic uveitis.
      In the other 15 patients, the underlying disease was juvenile idiopathic
      arthritis in 12 (57%), Behcet disease in two (9%) and sarcoidosis in one (5%).
      Response to etanercept treatment was good in 27%, moderate in 27% and poor in 45%
      of patients. Response to infliximab treatment was good in 38%, moderate in 54%
      and poor in 8% of patients. The difference in the percentage of patients with a
      moderate or good response was statistically significant (P = 0.0481). We also
      observed a lower rate of complications, such as new-onset or worsening glaucoma
      or cataract in the infliximab-treated group. CONCLUSION: Anti-TNF-alpha treatment
      was beneficial in a high percentage of patients with childhood uveitis refractory
      to standard immunosuppressive treatment. Infliximab resulted in better clinical
      responses with less ocular complications than etanercept.

PMID- 16461436
TI  - Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by the aberrant
      activation of T lymphocytes. Since T-bet and GATA-3 are the principal
      transcription factors for the differentiation of type-1 and type-2 helper T
      lymphocytes, respectively, we studied their mRNA expression in the urinary
      sediment of SLE patients and compared this with their urinary and intra-renal
      protein expression. METHODS: We studied 100 SLE patients and 10 healthy subjects.
      Urinary mRNA expression of T-bet and GATA-3 were studied by the real-time
      quantitative polymerase chain reaction. Intra-renal and urinary expressions of T
      bet and GATA-3 were studied by immunohistochemistry and western blotting,
      respectively. RESULTS: The urinary mRNA and protein expressions of T-bet were
      significantly higher in SLE patients with active nephritis than those with
      inactive disease (mRNA: P < 0.001; protein: P = 0.004). The urinary mRNA
      expression of T-bet correlated with the SLE disease activity index (SLEDAI) score
      (r = 0.55, P < 0.001) and the histological activity index (r = 0.48, P = 0.03).
      On the other hand, the urinary mRNA and protein expressions of GATA-3 were
      significantly lower in SLE patients with active nephritis (mRNA: P < 0.001;
      protein: P = 0.006), and GATA-3 mRNA expression inversely correlated with the
      SLEDAI score (r = 0.38, P < 0.001). For the 22 SLE patients with kidney biopsy,
      tubular expressions of T-bet and GATA-3 significantly correlated with the
      histological activity index (T-bet: r = 0.57, P = 0.006; GATA-3: r = -0.79, P <
      0.001). CONCLUSIONS: Patients with active lupus nephritis have increased T-bet
      and depressed GATA-3 expression in the urinary sediment and kidney tissue,
      indicating a predominant Th1 type of T-lymphocyte activation.

PMID- 16461437
TI  - The relationship of medical, demographic and psychosocial factors to direct and
      indirect health utility instruments in rheumatoid arthritis.
AB  - OBJECTIVES: Cost-effectiveness analysis (CEA) is essential for the comparison of
      treatments for rheumatoid arthritis (RA). CEA centres on accurate measurement of
      health utility (HU) preferences. Direct measures of HU in RA patients demonstrate
      weaker correlations with health status (functional disability and pain) than
      indirect measures. We examined whether demographic and psychosocial factors
      relate to HU in RA patients. METHODS: HU was measured for 142 RA patients (76%
      women; mean age 58.75 yr) directly through standard gamble (SG) and time trade
      off (TTO), and indirectly on the EuroQol (EQ-5D). Current pain (100 mm visual
      analogue scale) and recent functional disability (Health Assessment
      Questionnaire; HAQ) were assessed. A subsample of 48 provided demographic and
      psychosocial information (education, employment, marital/family status, knowledge
      about RA, medication beliefs, desirable responding, social support, optimism, and
      the Hospital Anxiety and Depression Scale; HADS). RESULTS: Direct HU had higher
      means (SG = 0.88, TTO = 0.86) than indirect HU (EQ-5D = 0.52). HAQ functional
      disability correlated with SG (r = - 0.28), TTO (r = - 0.31) and EQ-5D (r = -
      0.67). Current pain correlated with TTO (r = - 0.19) and EQ-5D (r = - 0.36). HADS
      depression correlated with TTO (r = - 0.35) and EQ-5D (r = - 0.64); HADS anxiety
      also correlated with EQ-5D (r = - 0.46). CONCLUSIONS: Demographic and
      psychosocial factors cannot completely explain either the significant differences
      between direct and indirect HUs in RA patients or the moderate correlations of
      direct HUs with health status. Characteristics of the SG and TTO may make them
      inappropriate for HU assessment and CEA among RA patients.

PMID- 16461438
TI  - The relationships of musculoskeletal disease to age, pain, poverty and behaviour.

PMID- 16461439
TI  - Combination of immunoadsorption and CD20 antibody therapy in a patient with mixed
      connective tissue disease.

PMID- 16461440
TI  - Therapy switching and associated costs in elderly patients receiving COX-2
      selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in
      Quebec, Canada.
AB  - OBJECTIVES: Lack of efficacy or tolerability of some non-steroidal anti
      inflammatory drugs (NSAIDs) may lead to switching between non-selective NSAIDs
      (nsNSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs),
      potentially increasing treatment costs due to additional physician visits and
      wastage of medication. This study assessed drug switching and associated costs
      among elderly chronic NSAID users. METHODS: Data for patients who filled their
      first prescription for a coxib or nsNSAID in 2001 were obtained from the Quebec
      Health Insurance Agency. Follow-up was terminated at the earliest of: 1 yr, the
      first day without NSAID exposure following the index filling date, or death.
      Patients could switch NSAIDs several times during follow-up. Person-days of
      exposure were categorized by the NSAID most recently dispensed: rofecoxib,
      celecoxib, Arthrotec(R) or non-Arthrotec (nA) nsNSAID. Cox regression models
      compared time to switch between groups, adjusting for patient baseline
      characteristics. Upon a switch, pills remaining from the previous prescription
      were considered wasted. The costs of wasted pills and switch-associated physician
      visits were estimated. RESULTS: Throughout follow-up, patients filled 38 267
      prescriptions for rofecoxib, 31 282 for celecoxib, 1108 for Arthrotec and 4388
      for nA-nsNSAIDs. Adjusted hazard ratios (95% confidence interval) for switching
      versus nA-nsNSAIDs were: rofecoxib, 0.39 (0.35-0.44); celecoxib, 0.43 (0.38
      0.48). Compared with nA-nsNSAID prescriptions, adjusted switching-related
      healthcare costs were 53 and 47% lower on average for rofecoxib and celecoxib
      prescriptions, respectively. These costs were 34% higher for Arthrotec
      prescriptions than for nA-nsNSAIDs. CONCLUSIONS: Compared with recipients of
      nsNSAIDs, coxib recipients were less likely to switch medications and had
      approximately half the adjusted costs for switching-related wasted resources per
      prescription.

PMID- 16461441
TI  - Performance-based methods for measuring the physical function of patients with
      osteoarthritis of the hip or knee: a systematic review of measurement properties.
AB  - OBJECTIVE: To systematically review the measurement properties (i.e. internal
      consistency, reproducibility, validity, responsiveness and interpretability) of
      all performance-based methods which have been used to measure the physical
      function of patients with osteoarthritis of the hip or knee. METHODS: A
      systematic search was conducted in Medline, CINAHL, PsychINFO and Embase.
      Standardized criteria were applied to assess the quality of the clinimetric
      studies and the measurement properties. RESULTS: Twenty-six performance-based
      methods were included: 13 walking tests, two stair-climb tests, one chair test
      and ten multi-item tests. Three out of seven multi-activity tests were tested for
      internal consistency and two were rated positively. Fourteen tests were tested
      for reliability and five were rated positively. The absolute measurement error
      (agreement) was assessed for 10 tests. Only one test received a positive rating.
      Fourteen tests were tested for construct validity. Only two tests received
      positive ratings. Responsiveness was assessed for 12 tests, but none of them
      received a positive rating. A lot of indeterminate ratings were given, mostly for
      small studies or non-optimal analyses. CONCLUSION: Many more well-designed
      studies are needed to assess the measurement properties of performance-based
      methods. More importantly, however, before one can make a justified choice of a
      particular performance-based method, consensus is needed on what activities
      should be included in a performance-based test for patients with hip or knee
      osteoarthritis and which aspects of function should be measured.

PMID- 16461442
TI  - Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and
      arthritis in systemic lupus erythematosus.
AB  - OBJECTIVE: The objective of this study was to confirm whether polymorphisms of
      the poly(ADP-ribose) polymerase gene (PARP) are associated with genetic
      susceptibility to systemic lupus erythematosus (SLE) and to investigate the
      possible association of nephritis and arthritis in SLE with PARP polymorphisms.
      METHODS: Using direct DNA sequencing in 24 individuals, we identified 44 sequence
      variants within exons and their flanking regions, including the 1.5-kb promoter
      region of PARP. Six common polymorphic sites were selected for larger-scale
      genotyping (in 350 Korean SLE patients and 330 healthy controls), which
      identified six common haplotypes. RESULTS: Although no statistically significant
      association with the risk of SLE was observed, we found that two single
      nucleotide polymorphisms (SNPs -1963A --> G and +28077G --> A) were significantly
      associated with an increased risk of nephritis, and one non-synonymous variant
      [+40329T --> C(V762A)] was also significantly associated with an increased risk
      of arthritis, while the -1963A --> G SNP showed a protective effect on arthritis
      in Korean SLE patients. CONCLUSION: Our results demonstrate that PARP
      polymorphisms are not associated with SLE susceptibility, but that -1963A --> G,
      +28077G --> A and +40329T --> C(V762A) are significantly associated with
      nephritis and arthritis in Korean SLE patients.

PMID- 16461443
TI  - The management of knee pain in primary care: factors associated with consulting
      the GP and referrals to secondary care.
AB  - OBJECTIVES: To investigate the treatment of knee pain in primary care and the
      factors associated with consulting general practitioners (GPs) and referrals to
      specialist services. METHODS: Individuals with knee pain were identified through
      postal questionnaires sent to patients aged 50 and over from two GP practices in
      southeast London. Patients with knee pain were then invited to the department,
      where demographic, clinical and service use data were collected. Participants
      also completed measures of pain, function, handicap and illness beliefs. RESULTS:
      From the 2940 questionnaires that were sent out, the response rate was 34%. Of
      these, 49% reported experiencing knee pain in the previous 12 months. Two hundred
      and thirty-one patients with knee pain attended the department. One hundred and
      thirty-four (58%) had seen their GP about their knee pain, with 50 (37%) referred
      on to specialist services. Compared with non-consulters, consulters had more
      severe disease and higher levels of disability and handicap, and believed the
      condition was more severe and had major consequences on their lives. Those
      referred to specialist care had higher levels of handicap and also believed the
      condition was more severe, with major consequences on their lives, than those not
      referred. CONCLUSION: In this sample nearly half of those who reported knee pain
      had not seen their GP and were self-managing their condition. A mixture of
      physical, social and psychological factors predicted visits to GPs and rates of
      referral to secondary care. Patient perceptions about knee pain were important
      predictors of both consultations and referrals, highlighting the need to address
      both physical and psychosocial factors in relation to help-seeking.

PMID- 16461444
TI  - Chest pain in general practice: incidence, comorbidity and mortality.
AB  - BACKGROUND: Chest pain is a common symptom that presents the primary care
      physician with a complex diagnostic and therapeutic challenge. AIMS: To evaluate
      the natural history and management of patients diagnosed with chest pain of
      unspecified type or origin in primary care. DESIGN: Population-based case-control
      study. METHODS: The study included 13,740 patients with a first diagnosis of
      unspecified chest pain and 20,000 age- and sex-matched controls identified from
      the UK General Practice Research Database. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were computed using unconditional logistic regression. Risk
      estimates were adjusted for age, sex and number of physician visits. RESULTS: The
      incidence of a new diagnosis of chest pain was 15.5 per 1000 person-years and
      increased with age, particularly in men. The risk of a chest pain diagnosis was
      greatest in patients with prior diagnoses of coronary heart disease (OR: 7.1; 95%
      CI: 6.1-8.2) and gastroesophageal reflux disease (OR: 2.0; 95% CI: 1.7-2.3). In
      the year after diagnosis, chest pain patients were more likely than controls to
      be newly diagnosed with coronary heart disease (OR: 14.9; 95% CI: 12.7-17.4) and
      heart failure (OR: 4.7; 95% CI: 3.6-6.1). A new diagnosis of chest pain was
      associated with an increased risk of death in the following year (RR: 2.3; 95%
      CI: 1.9-2.8). CONCLUSIONS: Some causes of chest pain are underdiagnosed in
      primary care. This is of particular consequence for the minority of chest pain
      patients with cardiac disease.

PMID- 16461445
TI  - Management of upper respiratory tract infections in Dutch general practice;
      antibiotic prescribing rates and incidences in 1987 and 2001.
AB  - BACKGROUND AND AIM: This study aims to assess differences in antibiotic
      prescribing and incidence of Upper Respiratory Tract Infections (URTIs) between
      1987 and 2001, before (1987) and after (2001) publication of Dutch guidelines on
      URTIs. DESIGN, SETTING AND METHOD: Data were collected in two national surveys:
      96 general practices (n=344,449 patients) in 1987 and 90 general practices
      (n=358,008 patients) in 2001. Outcome measures were: (1) antibiotic prescribing
      rates for acute otitis media (AOM), common cold, sinusitis and acute tonsillitis;
      (2) number of antibiotic prescriptions per 1000 patients per year; (3) incidence
      rates per 1000 patients per year. RESULTS: Antibiotic prescribing rates in AOM
      and common cold were increased in 2001 compared to 1987 (from 27% to 48%; from
      17% to 23%, respectively), while the rates for sinusitis and acute tonsillitis
      were about the same (72% and 70%; 74% and 72%, respectively). Except for AOM, the
      number of antibiotic prescriptions per 1000 patients decreased by 30% to 50%. As
      incidence rates of common cold, tonsillitis and sinusitis decreased, the decline
      in the total volume of antibiotic prescriptions per 1000 patients for these three
      categories has mainly to be attributed to a fall of incidence rates. CONCLUSION:
      Antibiotic prescribing rates for URTIs have not declined between 1987 and 2001,
      but the volumes for common cold, sinusitis and tonsillitis have fallen down
      mainly attributable to declined incidences, which have probably been caused by a
      reduced inclination of patients to present respiratory illness to their GP.
      Prescribing antibiotics for AOM has increased.

PMID- 16461446
TI  - The overdiagnosis of depression in non-depressed patients in primary care.
AB  - BACKGROUND: The underdiagnosis of depression is an important research topic.
      Nevertheless, overdiagnosis has not been given the importance it deserves by
      research into the ability of family physicians to diagnose depression correctly.
      OBJECTIVES: To identify the factors that determine the overdiagnosis of
      depression by family physicians and to evaluate the clinical significance of this
      error. DESIGN: Two-phase cross-sectional study. SETTING: Primary care centres in
      Tarragona (Spain). METHODS: In the first phase, we screened 906 consecutive
      patients using Zung's self-rating depression scale (SDS). In the second phase,
      all the 209 patients with a positive screening and 97 patients with a negative
      screening (1 out of 7 randomly) were given the Structured Clinical Interview for
      DSM-IV Disorders, a series of questionnaires, and the family physician judged
      whether depression was present. In the 186 patients for whom there were no
      criteria of major depression or dysthymia, the association of various variables
      with the physicians' overdiagnosis of depression was analysed. RESULTS: The rate
      of diagnosis of depression in non-depressed patients was 26.5% (95% CI: 19.0
      33.9). The factors associated independently with overdiagnosis were the SDS score
      (OR: 1.05; 95% CI: 1.01-1.10), the Global Assessment of Functioning score (OR:
      0.95; 95% CI: 0.90-0.99), previous history of depression (OR: 2.66; 95% CI: 1.12
      6.30) and presence of generalized anxiety (OR: 0.42; 95% CI: 0.18-0.97).
      CONCLUSION: Family physicians classify as depressed those patients who do not
      have the formal signs of depression but who do have antecedents of this disorder
      or a psychological distress that may be prodromal of future depressive episodes.

PMID- 16461447
TI  - Can doctors predict patients' satisfaction and enablement? A cross-sectional
      observational study.
AB  - BACKGROUND: Patient satisfaction surveys are increasingly used to measure
      consulting quality and outcome, but little is known of how good doctors are at
      judging their patients' satisfaction with their consultations. OBJECTIVES: To
      determine if patient satisfaction and enablement following a consultation are
      correlated with both inexperienced and experienced doctors' predictions of
      patient satisfaction and doctors' own satisfaction with the consultation.
      METHODS:  DESIGN: Cross-sectional questionnaire-based observational study.
      SETTING: Scottish general practices. MAIN OUTCOME MEASURES: Using a post
      consultation questionnaire we compared doctors' estimates of patient satisfaction
      with the consultation; doctors' own satisfaction with the consultation; scores on
      the Patient Enablement Instrument (PEI) and the Consultation Satisfaction
      Questionnaire (CSQ). RESULTS: Twenty-nine doctors and 1848 patients took part.
      Each doctor recorded an average of 63.7 (SD: 32.1) consultations. Patient
      measures of satisfaction and enablement were only weakly correlated with doctor
      predictions of patient satisfaction (rs=0.07 for PEI and 0.13 for CSQ; both
      P<0.01) or doctor satisfaction (rs=0.10 for PEI and 0.12 for CSQ; both P<0.01)
      with the consultation. They were, however, moderately well correlated (rs=0.50
      P<0.01) with one another. CONCLUSION: Doctors are poor at predicting patient
      satisfaction in the consultation. Further research is required to determine the
      reasons for this.

PMID- 16461448
TI  - The influence of GP and patient gender interaction on the duration of certified
      sickness absence.
AB  - BACKGROUND: Little research has focused upon how GP and patient gender interact
      to influence the outcome of consultation. In particular, no UK studies have
      investigated the effect of gender interaction on the duration of patients'
      certified sickness. OBJECTIVE: To investigate associations between the four GP
      patient gender interaction categories and patient risk of intermediate or long
      term work incapacity. METHODS:  DESIGN: Use of carbonized sickness certificates
      to collect routine sick note data over a 12-month collection period. SETTING:
      Nine general practices in the Mersey Primary Care R&D Consortium. SUBJECTS: A
      total of 3906 patients, certified sick by 67 GPs (including 45 GP principals).
      MAIN OUTCOME MEASURES: The effect of gender interaction was measured against two
      outcomes: intermediate (6-28 week) and long-term (28 weeks or over) periods of
      certified sickness. RESULTS: After univariate and multivariate analyses, it was
      discovered that certification of male patients by male GPs was significantly
      associated with increased prevalence of intermediate (6-28 week) certified
      sickness outcomes, compared with females certified by females (OR=1.38 P=0.009).
      This result was replicated in the subgroup of patients with mild mental disorder
      related sickness absence. However, no association was demonstrated between gender
      interaction and long-term (>or=28 week) outcome, in the total patient group or
      within diagnostic subcategories. CONCLUSION: GP and patient gender appear to have
      most impact upon sickness certification in the intermediate period. This period
      is already recognized as the optimum time for interventions to prevent onset of
      long-term incapacity, particularly in cases where the cause of sickness absence
      is reversible (as in psychological-related certified sickness absence). Further
      research is needed (particularly focusing upon attitudes and content of
      consultations) in order to shed more light on the gender differences found in
      this study.

PMID- 16461449
TI  - The response of general practitioners to the threat of violence in their
      practices: results from a qualitative study.
AB  - BACKGROUND: Violence directed towards GPs has been recognized as a significant
      problem in the UK. In Australian urban general practice, no study has previously
      examined this topic. OBJECTIVE: The objective of this study was to investigate
      the responses of Australian urban GPs to experiences of violence and to
      perceptions of risk of violence. METHODS:  DESIGN: A qualitative study of data
      collected from two sources-focus group discussions and qualitative questionnaire
      responses. Focus group discussions were audiotaped and transcribed.
      Questionnaires offered the opportunity for respondents to make qualitative
      comments. The focus group transcripts and qualitative questionnaire responses
      were coded independently by members of the research team and subjected to
      thematic analysis. SETTING: Three urban Divisions of General Practice in New
      South Wales, Australia. SUBJECTS: Focus groups were conducted with male and
      female GPs comprising a range of ages, socio-economic practice catchments and
      practice structures. Questionnaires were distributed to all GPs in the three
      divisions. RESULTS: The GPs in this study perceived themselves as being at
      significant risk of occupational violence. Despite responses to violence being
      largely ad hoc and uncoordinated, a coherent schema of GPs' responses to the
      threat of violence is apparent in the data. This has been characterized as
      encompassing primary, secondary and tertiary responses, and reflects a continuum
      of proactive to reactive responses. CONCLUSION: The findings will have
      implications for further research and for policy in the area.

PMID- 16461450
TI  - Obstacles to shared care for patients with dementia: a qualitative study.
AB  - BACKGROUND: All Primary Care Trusts in England were meant to have shared care
      protocols for antidementia medication use in place by 1 April 2004. Shared care
      of medical treatment in dementia depends upon early diagnosis, but under
      recognition of and under-response to dementia appear widespread in general
      practice. AIM: To investigate the perceptions of specialists and generalists
      about the potential for shared care of people with dementia. DESIGN OF STUDY:
      Qualitative study with semistructured interviews. SETTING: Three inner-city and
      two rural areas. METHODS: Semistructured interviews were arranged at the
      participants' convenience and were tape-recorded and transcribed. Thematic
      analysis of the anonymized transcripts was undertaken and a case and cross-case
      analysis was performed. RESULTS: Thirty-nine GPs and 30 specialists were
      interviewed. Broad themes were reduced to following four key categories which
      appear to be layered over each other: therapeutic nihilism; risk reduction or
      avoidance; concerns about competency; and resources for shared care. CONCLUSION:
      Roles for primary and secondary care professionals are inappropriately
      distributed and require clearer definition. Resistance to shared care mostly
      comes from within general practice and reflects concerns about staffing, time
      constraints, lack of experience and confidence in making and disclosing a
      diagnosis. Developers of shared care protocols must dissect layered obstacles,
      addressing the issues of therapeutic nihilism, risk management and clinical
      competence.

PMID- 16461451
TI  - Family involvement in the care of healthy medical outpatients.
AB  - BACKGROUND: Although the involvement of patients' family members in office visits
      has been examined extensively, less is known about the involvement of family
      members in supporting patients' medical care outside of office visits. OBJECTIVE:
      This study examines two questions: What types of family involvement do family
      members have in the medical care of relatively healthy older outpatients, and
      does self-rated health moderate patients' reactions to this family involvement?
      METHODS: Patients from a large sample of medical practice outpatients (N = 1572)
      were assessed to determine perceived emotional support, involvement of family
      members in their medical care, as well as the presence of depressive symptoms.
      RESULTS: Approximately 50% of patients had some family involvement in their
      medical care (e.g. taking part in medical decisions, reminding the patient to
      take medication). Marital status was a stronger predictor of family involvement
      than self-ratings of poor physical health. Additionally, there was no evidence
      that older patients who report good health have less favourable reactions to
      family involvement in their medical care. CONCLUSION: Family involvement in
      medical care occurs routinely and is most likely to involve a spouse, and is
      consistent with family interaction patterns among older adults. These findings
      also suggest that when providers invite family members to support treatment
      outside the office visit, these invitations are appropriate for older adult
      patients across a continuum of good to poor health.

PMID- 16461452
TI  - Family medicine attributes related to satisfaction, health and costs.
AB  - OBJECTIVE: To identify, from a systematic review of the literature, the
      attributes of Family Medicine (FM) that influence the primary health care outcome
      as measured by users' satisfaction, improvement in patient health and in costs.
      DATA SOURCES: Literature search of Medline and the Cochrane library using MeSH
      terms 'Primary Health' or 'Family Practice' or 'Family Physicians' and 'Outcome
      Assessment' or 'Process Assessment'. Papers were excluded if they lacked a based
      on primary data, if no single component of FM was assessed; if indicators of
      evaluation were not related to health, satisfaction or costs. RESULTS: A total of
      356 articles were initially identified and 19 finally met the inclusion criteria.
      Study methods were a systematic review of randomized control trials, a double
      blind randomized trial, 4 systematic reviews of observational studies, 2 cohort
      studies and 12 descriptive cross-sectional studies. CONCLUSIONS: There was
      evidence of relationships between the attributes of FM and the service outcomes
      measured by indicators of satisfaction, health and cost. User satisfaction was
      associated with accessibility, continuity of care, consultation time and the
      doctor-patient relationship. Improvement in patient's health was related to
      continuity, consultation time, doctor-patient relationship and the implementation
      of preventive activities. Coordination of care showed mixed results with health
      outcomes. Continuity, consultation time, doctor-patient communication and
      prevention were cost-effective in the primary care setting.

PMID- 16461453
TI  - Hyaluronan oligosaccharides induce cell death through PI3-K/Akt pathway
      independently of NF-kappaB transcription factor.
AB  - Several studies indicate that hyaluronan oligosaccharides (oHA) are able to
      modulate growth and cell survival in solid tumors; however, no studies have been
      undertaken to analyze the effect of oHA on T-lymphoid disorders. In this work we
      showed that oHA were able to induce apoptosis in lymphoma cell lines. Since PI3
      K/Akt and nuclear factor-kappaB (NF-kappaB) are major factors involved in cell
      survival and anti-apoptotic pathways in lymphoma cells, we hypothesized that oHA
      could induce apoptosis through inhibition of these pathways. oHA were identified
      by a method which allows characterization of length using a high pH anion
      exchange chromatography with pulse amperometric detection (HPAEC-PAD). oHA
      inhibited PIP(3) production (principal product of PI3-K activity) and reduced Akt
      phosphorylation levels, similarly to the specific inhibitor wortmannin. However,
      treatment with either oHA or wortmannin failed to inhibit constitutive NF-kappaB
      activity and modulate IkappaBalpha protein levels, suggesting that PI3-K and NF
      kappaB signaling pathways are not related in the cell lines used. Cell behavior
      differed using native hyaluronan (HA), which induced PIP(3) production, Akt
      phosphorylation, and NF-kappaB activation, although not related with cell
      survival since treatment with native HA showed no effect on apoptosis. Our
      results suggest that oHA induce apoptosis by suppression of PI3-K/Akt cell
      survival pathway without involving NF-kappaB activation, through a mechanism that
      differs from the one mediated by native HA.

PMID- 16461454
TI  - Unique, common, and interacting cortical correlates of thirst and pain.
AB  - This study used positron-emission tomography to establish the patterns of brain
      activity involved in the isolated and concurrent experiences of thirst and pain.
      Ten subjects were scanned while experiencing pain evoked with noxious pressure,
      while experiencing thirst after the infusion of hypertonic saline, and while
      experiencing pain when thirsty. After the onset of thirst, noxious pressure
      evoked more intense sensations of pain. Noxious pressure did not change
      subjective ratings of thirst. Thirst caused activation in the anterior cingulate
      (Brodmann area 32) and the insula. Enhanced pain responses were associated with
      increased activity in cortical regions that are known to correlate with pain
      intensity, and also with unique activity in the pregenual anterior cingulate and
      ventral orbitofrontal cortex. These findings suggest a role for limbic and
      prefrontal cortices in the modulation of pain during the experience of thirst.

PMID- 16461455
TI  - Structure and function of the SWIRM domain, a conserved protein module found in
      chromatin regulatory complexes.
AB  - The SWIRM domain is a module found in the Swi3 and Rsc8 subunits of SWI/SNF
      family chromatin remodeling complexes, and the Ada2 and BHC110/LSD1 subunits of
      chromatin modification complexes. Here we report the high-resolution crystal
      structure of the SWIRM domain from Swi3 and characterize the in vitro and in vivo
      function of the SWIRM domains from Saccharomyces cerevisiae Swi3 and Rsc8. The
      Swi3 SWIRM forms a four-helix bundle containing a pseudo 2-fold axis and a helix
      turn-helix motif commonly found in DNA-binding proteins. We show that the Swi3
      SWIRM binds free DNA and mononucleosomes with high and comparable affinity and
      that a subset of Swi3 substitution mutants that display growth defects in vivo
      also show impaired DNA-binding activity in vitro, consistent with a nucleosome
      targeting function of this domain. Genetic and biochemical studies also reveal
      that the Rsc8 and Swi3 SWIRM domains are essential for the proper assembly and in
      vivo functions of their respective complexes. Together, these studies identify
      the SWIRM domain as an essential multifunctional module for the regulation of
      gene expression.

PMID- 16461456
TI  - A pilot clinical trial of a recombinant ricin vaccine in normal humans.
AB  - Ricin, a highly potent toxin produced by castor beans, is classified by the
      Centers for Disease Control and Prevention as a level B biothreat because it is
      easily produced, readily available, and highly stable. There have been >750 cases
      of documented ricin intoxication in humans. There is no approved vaccine for
      ricin. Ricin contains a lectin-binding B chain and a ribotoxic A chain (RTA). In
      addition to its ribotoxic site, we have identified a separate site on RTA that is
      responsible for inducing vascular leak syndrome (VLS) in humans. We have
      generated a recombinant RTA with two amino acid substitutions that disrupt its
      ribotoxic site (Y80A) and its VLS-inducing site (V76M). This mutant recombinant
      RTA (named RiVax) was expressed and produced in Escherichia coli and purified.
      When RiVax was injected i.m. into mice it protected them against a ricin
      challenge of 10 LD50s. Preclinical studies in both mice and rabbits demonstrated
      that RiVax was safe. Based on these results, we have now conducted a pilot
      clinical trial in humans under an investigational new drug application submitted
      to the Food and Drug Administration. In this study, three groups of five normal
      volunteers were injected three times at monthly intervals with 10, 33, or 100 mug
      of RiVax. The vaccine was safe and elicited ricin-neutralizing Abs in one of five
      individuals in the low-dose group, four of five in the intermediate-dose group,
      and five of five in the high-dose group. These results justify further
      development of the vaccine.

PMID- 16461457
TI  - Gain-of-function/Noonan syndrome SHP-2/Ptpn11 mutants enhance calcium
      oscillations and impair NFAT signaling.
AB  - Gain-of-function mutations in SHP-2/PTPN11 cause Noonan syndrome, a human
      developmental disorder. Noonan syndrome is characterized by proportionate short
      stature, facial dysmorphia, increased risk of leukemia, and congenital heart
      defects in approximately 50% of cases. Congenital heart abnormalities are common
      in Noonan syndrome, but the signaling pathway(s) linking gain-of-function SHP-2
      mutants to heart disease is unclear. Diverse cell types coordinate cardiac
      morphogenesis, which is regulated by calcium (Ca2+) and the nuclear factor of
      activated T-cells (NFAT). It has been shown that the frequency of Ca2+
      oscillations regulates NFAT activity. Here, we show that in fibroblasts, Ca2+
      oscillations in response to FGF-2 require the phosphatase activity of SHP-2.
      Conversely, gain-of-function mutants of SHP-2 enhanced FGF-2-mediated Ca2+
      oscillations in fibroblasts and spontaneous Ca2+ oscillations in cardiomyocytes.
      The enhanced frequency of cardiomyocyte Ca2+ oscillations induced by a gain-of
      function SHP-2 mutant correlated with reduced nuclear translocation and
      transcriptional activity of NFAT. These data imply that gain-of-function SHP-2
      mutants disrupt the Ca2+ oscillatory control of NFAT, suggesting a potential
      mechanism for congenital heart defects in Noonan syndrome.

PMID- 16461458
TI  - Regulation of allergic airway inflammation through Toll-like receptor 4-mediated
      modification of mast cell function.
AB  - In a mouse experimental asthma model, the administration of bacterial
      lipopolysaccharide (LPS), particularly at low doses, enhances the levels of
      ovalbumin (OVA)-induced eosinophilic airway inflammation. In an effort to clarify
      the cellular and molecular basis for the LPS effect, we demonstrate that the OVA
      induced eosinophilic inflammation in the lung is dramatically increased by the
      administration of LPS in wild-type mice, whereas such increase was not observed
      in mast-cell-deficient mice or Toll-like receptor (TLR)4-deficient mice. Adoptive
      transfer of bone-marrow-derived mast cells (BMMCs) from wild-type, but not from
      TLR4-deficient, mice restored the increased eosinophilic inflammation in mast
      cell-deficient mice. Wild-type BMMCs pretreated with LPS in vitro also
      reconstituted the eosinophilic inflammation. Moreover, in vitro analysis revealed
      that the treatment of BMMCs with LPS resulted in NF-kappaB activation, sustained
      up-regulation of GATA1 and -2 expression, and increased the capability to produce
      IL-5 and -13. Dramatic increases in the expression of IL-5 and -13 and Eotaxin 2
      were detected in LPS-treated BMMCs after costimulation with LPS and IgE/Ag.
      Overexpression of GATA1, but not GATA2, in MC9 mast cells resulted in increased
      transcriptional activity of IL-4, -5, and -13. Furthermore, the levels of
      transcription of Th2 cytokines in BMMCs were decreased by the introduction of
      small interfering RNA for GATA1. Thus, mast cells appear to control allergic
      airway inflammation after their activation and modulation through TLR4-mediated
      induction of GATA1 and subsequent increase in Th2 cytokine production.

PMID- 16461459
TI  - Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of
      early inflammation in multiple sclerosis.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is an integral membrane protein
      expressed in CNS oligodendrocytes and outermost myelin lamellae. Anti-MOG Abs
      cause myelin destruction (demyelination) in animal models of multiple sclerosis
      (MS); however, such pathogenic Abs have not yet been characterized in humans.
      Here, a method that specifically detects IgG binding to human MOG in its native,
      membrane-embedded conformation on MOG-transfected mammalian cells was used to
      evaluate the significance of these auto Abs. Compared with healthy controls,
      native MOG-specific IgGs were most frequently found in serum of clinically
      isolated syndromes (P < 0.001) and relapsing-remitting MS (P < 0.01), only
      marginally in secondary progressive MS (P < 0.05), and not at all in primary
      progressive MS. We demonstrate that epitopes exposed in this cell-based assay are
      different from those exposed on the refolded, extracellular domain of human
      recombinant MOG tested by solid-phase ELISA. In marmoset monkeys induced to
      develop MS-like CNS inflammatory demyelination, IgG reactivity against the native
      membrane-bound MOG is always detected before clinical onset of disease (P <
      0.0001), unlike that against other myelin constituents. We conclude that (i)
      epitopes displayed on native, glycosylated MOG expressed in vivo are early
      targets for pathogenic Abs; (ii) these Abs, which are not detected in solid-phase
      assays, might be the ones to play a pathogenic role in early MS with predominant
      inflammatory activity; and (iii) the cell-based assay provides a practical
      serologic marker for early detection of CNS autoimmune demyelination including
      its preclinical stage at least in the primate MS model.

PMID- 16461460
TI  - A microRNA expression signature of human solid tumors defines cancer gene
      targets.
AB  - Small noncoding microRNAs (miRNAs) can contribute to cancer development and
      progression and are differentially expressed in normal tissues and cancers. From
      a large-scale miRnome analysis on 540 samples including lung, breast, stomach,
      prostate, colon, and pancreatic tumors, we identified a solid cancer miRNA
      signature composed by a large portion of overexpressed miRNAs. Among these miRNAs
      are some with well characterized cancer association, such as miR-17-5p, miR-20a,
      miR-21, miR-92, miR-106a, and miR-155. The predicted targets for the
      differentially expressed miRNAs are significantly enriched for protein-coding
      tumor suppressors and oncogenes (P < 0.0001). A number of the predicted targets,
      including the tumor suppressors RB1 (Retinoblastoma 1) and TGFBR2 (transforming
      growth factor, beta receptor II) genes were confirmed experimentally. Our results
      indicate that miRNAs are extensively involved in cancer pathogenesis of solid
      tumors and support their function as either dominant or recessive cancer genes.

PMID- 16461461
TI  - The role of the airline transportation network in the prediction and
      predictability of global epidemics.
AB  - The systematic study of large-scale networks has unveiled the ubiquitous presence
      of connectivity patterns characterized by large-scale heterogeneities and
      unbounded statistical fluctuations. These features affect dramatically the
      behavior of the diffusion processes occurring on networks, determining the
      ensuing statistical properties of their evolution pattern and dynamics. In this
      article, we present a stochastic computational framework for the forecast of
      global epidemics that considers the complete worldwide air travel infrastructure
      complemented with census population data. We address two basic issues in global
      epidemic modeling: (i) we study the role of the large scale properties of the
      airline transportation network in determining the global diffusion pattern of
      emerging diseases; and (ii) we evaluate the reliability of forecasts and outbreak
      scenarios with respect to the intrinsic stochasticity of disease transmission and
      traffic flows. To address these issues we define a set of quantitative measures
      able to characterize the level of heterogeneity and predictability of the
      epidemic pattern. These measures may be used for the analysis of containment
      policies and epidemic risk assessment.

PMID- 16461462
TI  - Mutation and genomic deletion status of ataxia telangiectasia mutated (ATM) and
      p53 confer specific gene expression profiles in mantle cell lymphoma.
AB  - Although mantle cell lymphoma (MCL) frequently harbors inactivated ataxia
      telangiectasia mutated (ATM) and p53 alleles, little is known about the molecular
      phenotypes caused by these genetic changes. We identified point mutations and
      genomic deletions in these genes in a series of cyclin D1-positive MCL cases and
      correlated genotype with gene expression profiles and overall survival. Mutated
      and/or deleted ATM and p53 alleles were found in 56% (40/72) and 26% (21/82) of
      the cases examined, respectively. Although MCL patients with inactive p53 alleles
      showed a significant reduction in median overall survival, aberrant ATM status
      did not predict for survival. Nevertheless, specific gene expression signatures
      indicative of the mutation and genomic deletion status of each gene were
      identified that were different from wild-type cases. These signatures were
      comprised of a select group of genes related to apoptosis, stress responses, and
      cell cycle regulation that are relevant to ATM or p53 function. Importantly, we
      found the molecular signatures are different between cases with mutations and
      deletions, because the latter are characterized by loss of genes colocalized in
      the same chromosome region of ATM or p53. This information on molecular
      phenotypes may provide new areas of investigation for ATM function or may be
      exploited by designing specific therapies for MCL cases with p53 aberrations.

PMID- 16461463
TI  - Dictyostelium myosin II mechanochemistry promotes active behavior of the cortex
      on long time scales.
AB  - Cell cortices rearrange dynamically to complete cytokinesis, crawlin response to
      chemoattractant, build tissues, and make neuronal connections. Highly enriched in
      the cell cortex, actin, myosin II, and actin crosslinkers facilitate cortical
      movements. Because cortical behavior is the consequence of nanoscale biochemical
      events, it is essential to probe the cortex at this level. Here, we use high
      resolution laser-based particle tracking to examine how myosin II
      mechanochemistry and dynacortin-mediated actin crosslinking control cortex
      dynamics in Dictyostelium. Consistent with its low duty ratio, myosin II does not
      directly drive active bead motility. Instead, myosin II and dynacortin
      antagonistically regulate other active processes in the living cortex.

PMID- 16461464
TI  - A genetic locus required for iron acquisition in Mycobacterium tuberculosis.
AB  - Mycobactins are a family of membrane-associated siderophores required for
      Mycobacterium tuberculosis to adapt to its intracellular habitat. These
      lipophilic siderophores have been recently shown to directly acquire
      intracellular iron through lipid trafficking. Despite tremendous progress in
      understanding the assembly-line enzymology of the siderophore biosynthesis, the
      genes as well as the mechanistic and biochemical principles involved in producing
      membrane-associated siderophores have not been investigated. Here, we report a
      biosynthetic locus that incorporates variety of aliphatic chains on the
      mycobactin skeleton. Cell-free reconstitution studies demonstrate that these acyl
      chains are directly transferred from a carrier protein on to the epsilon-amino
      group of lysine residue by an unidentified Rv1347c gene product. The unsaturation
      in the lipidic chain is produced by a novel acyl-acyl carrier protein
      dehydrogenase, which, in contrast to the conventional acyl-CoA dehydrogenases, is
      involved in the biosynthetic pathway. MbtG protein then performs the final N6
      hydroxylation step. Genome-wide analysis revealed homologues of N-acyl
      transferase and MbtG in other pathogenic bacteria. Because iron plays a key role
      in the development of infectious diseases, the biosynthetic pathway described
      here represents an attractive target for developing new antibacterial agents.

PMID- 16461465
TI  - The Kadison-Singer problem in mathematics and engineering.
AB  - We will see that the famous intractible 1959 Kadison-Singer Problem in C*
      algebras is equivalent to fundamental open problems in a dozen different areas of
      research in mathematics and engineering. This work gives all these areas common
      ground on which to interact as well as explaining why each area has volumes of
      literature on their respective problems without a satisfactory resolution.

PMID- 16461466
TI  - FRET imaging reveals that functional neurokinin-1 receptors are monomeric and
      reside in membrane microdomains of live cells.
AB  - The lateral organization of a prototypical G protein-coupled receptor, the
      neurokinin-1 receptor (NK1R), was investigated in living cells by fluorescence
      resonance energy transfer (FRET) microscopy, taking advantage of the recently
      developed acyl carrier protein (ACP) labeling technique. The NK1R was expressed
      as fusion protein with ACP to which small fluorophores were then covalently
      bound. Our approach allowed the recording of FRET images of receptors on living
      cells with unprecedented high signal-to-noise ratios and a subsequent unequivocal
      quantification of the FRET data owing to (i) the free choice of optimal
      fluorophores, (ii) the labeling of NK1Rs exclusively on the cell surface, and
      (iii) the precise control of the donor-acceptor molar ratio. Our single-cell FRET
      measurements exclude the presence of constitutive or ligand-induced homodimers or
      oligomers of NK1Rs. The strong dependence of FRET on the receptor concentration
      further reveals that NK1Rs tend to concentrate in microdomains, which are found
      to constitute approximately 1% of the cell membrane and to be sensitive to
      cholesterol depletion.

PMID- 16461467
TI  - An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of
      PPARgamma, adipogenesis, and insulin-responsive hexose transport.
AB  - The insulin-regulated glucose transporter GLUT4 is a key modulator of whole body
      glucose homeostasis, and its selective loss in adipose tissue or skeletal muscle
      causes insulin resistance and diabetes. Here we report an RNA interference-based
      screen of protein kinases expressed in adipocytes and identify four negative
      regulators of insulin-responsive glucose transport: the protein kinases PCTAIRE-1
      (PCTK1), PFTAIRE-1 (PFTK1), IkappaB kinase alpha, and MAP4K4/NIK. Integrin-linked
      protein kinase was identified as a positive regulator of this process. We
      characterized one of these hits, MAP4K4/NIK, and found that it is unique among
      mitogen-activated protein (MAP) kinases expressed in cultured adipocytes in
      attenuating hexose transport. Remarkably, MAP4K4/NIK suppresses expression of the
      adipogenic transcription factors C/EBPalpha, C/EBPbeta, and PPARgamma and of
      GLUT4 itself in these cells. RNA interference-mediated depletion of MAP4K4/NIK
      early in differentiation enhances adipogenesis and triglyceride deposition, and
      even in fully differentiated adipocytes its loss up-regulates GLUT4. Conversely,
      conditions that inhibit adipogenesis such as TNF-alpha treatment or depletion of
      PPARgamma markedly up-regulate MAP4K4/NIK expression in cultured adipocytes.
      Furthermore, TNF-alpha signaling to down-regulate GLUT4 is impaired in the
      absence of MAP4K4/NIK, indicating that MAP4K4 expression is required for optimal
      TNF-alpha action. These results reveal a MAP4K4/NIK-dependent signaling pathway
      that potently inhibits PPARgamma-responsive gene expression, adipogenesis, and
      insulin-stimulated glucose transport.

PMID- 16461468
TI  - Parenteral nutrition: ethical and legal considerations.
AB  - Parenteral nutrition is an expensive therapeutic modality that is used to treat
      patients with intestinal failure. The benefit it offers in terms of life
      prolongation needs to be weighed against its risks and burdens. Through the use
      of descriptive clinical vignettes, this article illustrates the ethical and legal
      principles that underpin decisions to administer and, more importantly, to
      withhold or withdraw parenteral nutrition.

PMID- 16461469
TI  - Ageing and the brain.
AB  - Ageing causes changes to the brain size, vasculature, and cognition. The brain
      shrinks with increasing age and there are changes at all levels from molecules to
      morphology. Incidence of stroke, white matter lesions, and dementia also rise
      with age, as does level of memory impairment and there are changes in levels of
      neurotransmitters and hormones. Protective factors that reduce cardiovascular
      risk, namely regular exercise, a healthy diet, and low to moderate alcohol
      intake, seem to aid the ageing brain as does increased cognitive effort in the
      form of education or occupational attainment. A healthy life both physically and
      mentally may be the best defence against the changes of an ageing brain.
      Additional measures to prevent cardiovascular disease may also be important.

PMID- 16461470
TI  - Medical and surgical management of priapism.
AB  - Priapism is a pathological condition of penile erection that persists beyond, or
      is unrelated to, sexual stimulation. Pathologically and clinically, two subtypes
      are seen-the high flow (non-ischaemic) variety and the low flow (ischaemic)
      priapism. The low flow type is more dangerous, as these patients are susceptible
      to greater complications and the long term recovery of erectile function is
      dependent on prompt and urgent intervention. Many of the causes of priapism are
      medical, including pharmacological agents, and as such, priapism should be
      considered as a medical and surgical emergency.

PMID- 16461471
TI  - Diabetic neuropathy.
AB  - Diabetic neuropathy (DN) refers to symptoms and signs of neuropathy in a patient
      with diabetes in whom other causes of neuropathy have been excluded. Distal
      symmetrical neuropathy is the commonest accounting for 75% DN. Asymmetrical
      neuropathies may involve cranial nerves, thoracic or limb nerves; are of acute
      onset resulting from ischaemic infarction of vasa nervosa. Asymmetric
      neuropathies in diabetic patients should be investigated for entrapment
      neuropathy. Diabetic amyotrophy, initially considered to result from metabolic
      changes, and later ischaemia, is now attributed to immunological changes. For
      diagnosis of DN, symptoms, signs, quantitative sensory testing, nerve conduction
      study, and autonomic testing are used; and two of these five are recommended for
      clinical diagnosis. Management of DN includes control of hyperglycaemia, other
      cardiovascular risk factors; alpha lipoic acid and L carnitine. For neuropathic
      pain, analgesics, non-steroidal anti-inflammatory drugs, antidepressants, and
      anticonvulsants are recommended. The treatment of autonomic neuropathy is
      symptomatic.

PMID- 16461472
TI  - Treating vascular risk factors and maintaining vascular health: is this the way
      towards successful cognitive ageing and preventing cognitive decline?
AB  - Dementia is a progressive disorder that typically worsens with time and from
      which recovery is unlikely. The incidence of dementia increases exponentially
      with ageing and is an important public health challenge. There is now growing
      evidence for the role of vascular factors in Alzheimer's disease, mixed dementia
      (Alzheimer's disease with cerebrovascular disease), and of course vascular
      dementia. With the rising prevalence of vascular disease, there are increasing
      numbers of people who are identified to be at risk of cognitive impairment. By
      changing modifiable vascular risk factors, there is emerging evidence that it may
      be possible to prevent or delay the expression and progression of dementia.

PMID- 16461473
TI  - Management of acute renal failure.
AB  - Acute renal failure is a common condition, frequently encountered in both
      community practice and hospital inpatients. While it remains a heterologous
      condition, following basic principles makes investigation straightforward, and
      initial management follows a standard pathway in most patients. This article
      shows this, advises on therapeutic strategies, including those in special
      situations, and should help the clinician in deciding when to refer to a
      nephrologist, and when to consider renal replacement therapy.

PMID- 16461474
TI  - Modern management of arrhythmias.
AB  - The specialist management of arrhythmias has changed significantly over the past
      decade. This article outlines current management strategies for atrial flutter
      and atrial fibrillation, with particular emphasis on curative strategies with
      catheter ablation and the recent data on rhythm compared with rate control
      strategies. The expanding role of catheter ablation in the treatment of a wide
      variety of supraventricular and ventricular arrhythmias is discussed. The current
      evidence for implantable cardioverter defibrillators in the prevention of sudden
      cardiac death is summarised. The article also highlights the increasing
      recognition of a number of inherited syndromes that predispose to sudden cardiac
      death (for example, Brugada and long QT syndromes).

PMID- 16461475
TI  - Uroscopic rainbow: modern matula medicine.
AB  - Visual inspection of a patient's urine has long been used by physicians, with
      colour recognised as having important clinical implications. In this review the
      authors will revisit this ancient pastime with relevance to contemporary medical
      practice.

PMID- 16461476
TI  - Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on
      expression of trefoil factor 3, interleukin 1beta, and nuclear factor kappaB in
      trinitrobenzene sulphonic acid induced colitis in rats.
AB  - BACKGROUND AND AIMS: Butyrate enemas have been shown to be effective in treatment
      of ulcerative colitis, but the mechanism of the effects of butyrate is not
      totally known. This study evaluates effects of topical treatment of sodium
      butyrate (NaB) and 5-aminosalicylic acid (5-ASA) on the expression of trefoil
      factor 3 (TFF3), interleukin 1beta (IL1beta), and nuclear factor kappaB
      (NFkappaB) in trinitrobenzene sulphonic acid (TNBS) induced colitis in rats.
      METHODS: Distal colitis was induced in male Wistar rats by colonic administration
      of TNBS and colonically treated with NaB, 5-ASA, combination of NaB and 5-ASA,
      and normal saline for 14 consecutive days. Colonic damage score, tissue
      myeloperoxidase (MPO) activity, TFF3 mRNA expression, serum IL1beta production,
      and tissue NFkappaB expression were determined, respectively. RESULTS: Treatment
      of NaB, 5-ASA, and the combination improved diarrhoea, colonic damage score, and
      MPO activities, increased TFF3 mRNA expression, and decreased serum IL1beta
      production and tissue NFkappaB expression. The combination therapy of NaB and 5
      ASA had better effects than any other single treatment. CONCLUSIONS: The
      combination of topical treatment of NaB and 5-ASA was effective for relieving and
      repairing colonic inflammation and the effects were related to stimulation of
      TFF3 mRNA expression and down-regulation of IL1beta production and NFkappaB
      expression.

PMID- 16461477
TI  - Incidence and risk factors for development of venous thromboembolism in Indian
      patients undergoing major orthopaedic surgery: results of a prospective study.
AB  - INTRODUCTION: The incidence of venous thromboembolism (VTE) in Western
      populations undergoing major orthopaedic surgery without any thromboprophylaxis
      has been reported to range from 32% to 88%. There is however limited information
      on incidence of VTE in Indian patients and most of the Indian patients undergoing
      these surgeries do not receive any form of prophylaxis regardless of their risk
      profile. METHODS: A prospective study was performed on 147 patients undergoing
      major orthopaedic surgery for total knee replacement (TKR), total hip replacement
      (THR), and proximal femur fracture fixation (PFF) without any prophylaxis. These
      patients were profiled for presence of the known risk factors responsible for
      development of VTE. A duplex ultrasound on both lower limbs was done 6 to 10 days
      after surgery. Twenty three patients underwent THR, 22 patients underwent TKR,
      and 102 underwent surgery for PFF. The patients were assessed clinically for any
      signs of deep venous thrombosis (DVT) and pulmonary embolism (PE). A helical CT
      scan was done in case of suspicion of PE and a duplex ultrasound was done in case
      of clinical suspicion of DVT irrespective of the stage of study. RESULTS: The
      overall incidence of VTE was 6.12% and that of PE was 0.6%. The risk factors that
      were found to be significantly responsible for development of VTE (p < 0.05)
      were: immobility greater than 72 hours, malignancy, obesity, surgery lasting more
      than two hours. CONCLUSION: The study reconfirms the belief that DVT has a lower
      incidence in Indian patients as compared with other ethnic groups.

PMID- 16461478
TI  - Cardiovascular complications of severe acute respiratory syndrome.
AB  - BACKGROUND AND AIMS: Severe acute respiratory syndrome (SARS) is a virulent viral
      infection that affects a number of organs and systems. This study examined if
      SARS may result in cardiovascular complications. METHODS AND RESULTS: 121
      patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed
      continuously for blood pressure, pulse, and temperature during their stay in
      hospital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found
      in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week,
      respectively. Only one patient who had transient echocardiographic evidence of
      impaired left ventricular systolic function required temporary inotropic support.
      Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%,
      and 35.5% of patients from the first to third week. It occurred independent of
      hypotension, and could not be explained by the presence of fever. Tachycardia was
      also present in 38.8% of patients at follow up. Bradycardia only occurred in 18
      (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13
      (10.7%) patients, but without clinical evidence of heart failure. Transient
      atrial fibrillation was present in one patient. Corticosteroid therapy was weakly
      associated with tachycardia during the second (chi(2) = 3.99, p = 0.046) and
      third week (chi(2) = 6.53, p = 0.01), although it could not explain tachycardia
      during follow up. CONCLUSIONS: In patients with SARS, cardiovascular
      complications including hypotension and tachycardia were common but usually self
      limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia
      was rare. However, only tachycardia persisted even when corticosteroid therapy
      was withdrawn.

PMID- 16461479
TI  - Analysis of predictors of success in the MRCP (UK) PACES examination in
      candidates attending a revision course.
AB  - OBJECTIVE: To determine factors that predict success of candidates taking a
      revision course in preparation for the MRCP (UK) PACES (practical assessment of
      clinical examination skills) examination. DESIGN: A questionnaire survey of
      candidates attending a PACES revision course. Results were correlated with
      subsequent pass lists published by the Colleges of Physicians. SETTING AND
      SUBJECTS: Candidates attending courses in June and October 2002. In total, 523
      candidates completed questionnaires, evenly balanced between UK and overseas
      graduates. RESULTS: Of 483 candidates who took the examination immediately after
      the course, 219 (45.3%) passed. UK graduates were more likely to pass (67.0%)
      than overseas graduates (26.2%) (p = 0.003, odds ratio 5.72). For UK graduates,
      pass rates were higher for white candidates (73%) than for ethnic minorities
      (56%) (p = 0.012, OR 2.15) and for those who passed at the first attempt in the
      MRCP (UK) part 2 written paper (p = 0.003, OR 2.90). For overseas graduates,
      those who had been qualified for less than eight years were more likely to pass
      (p = 0.001, OR 2.78). More overseas (45.7%) than UK (30.8%) graduates were
      confident that they would pass, but confidence did not predict success.
      CONCLUSION: Among candidates taking a revision course, UK graduates are more
      likely to pass the PACES examination than non-UK graduates. Ethnic minority UK
      graduates seem to have a significantly poorer success rate, although this
      requires confirmation in an independent sample. If confirmed, these differences
      merit further investigation to assess whether they reflect genuine differences in
      ability.

PMID- 16461480
TI  - Retrospective analysis of the use of inferior vena cava filters in routine
      hospital practice.
AB  - INTRODUCTION: Characteristics and outcomes of patients undergoing inferior vena
      cava (IVC) filter insertion are not well reported. Particularly, the role of long
      term anticoagulation in these patients is unclear. AIMS: (1) To describe in a
      cohort of patients undergoing IVC filter insertion, underlying diseases,
      indications for filter insertion, complications, and survival. (2) To determine
      the effect of long term anticoagulant treatment on thromboembolism and patient
      survival. STUDY DESIGN: A retrospective analysis of 109 consecutive patients
      undergoing IVC filter insertion in two university hospitals. RESULTS: Average age
      was 67.4 years. Median duration of follow up was two years. Indications for IVC
      filter insertion were: contraindication to anticoagulation (n = 61, 56%),
      prophylactic insertion (n = 29, 27%), thromboembolism while receiving adequate
      anticoagulation (n = 17, 15%), and non-compliance with anticoagulation (n = 2,
      2%). Insertion related complications were groin haematoma in four patients (3.5%)
      and localised infection at the puncture site in one patient (0.9%). Fifty six
      patients (51.4%) died during the study period. Of these, 22 received long term
      anticoagulants and 34 did not. Overall and thrombosis free survival was greater
      in the anticoagulant treated group (median survival not reached) than in the
      untreated group (median survival = 12 months). Patients not receiving long term
      anticoagulation after IVC filter insertion were nearly 2.5-fold more likely to
      die or experience venous thromboembolism. CONCLUSION: IVC filter insertion was a
      safe procedure and was performed for appropriate indications in the patients
      studied. In patients surviving for longer than 30 days, prolonged administration
      of oral anticoagulants was associated with improved survival with no significant
      increase in haemorrhagic complications.

PMID- 16461481
TI  - Portrayal of negative qualities in a doctor as a potential teaching tool in
      medical ethics and humanism: Journey to the End of Night by Louis-Ferdinand
      Celine.
AB  - Fictional stories about physicians and patients are increasingly used as a
      powerful teaching resource for medical students. Very often, but not exclusively,
      stories of physicians as positive role models are selected to teach students
      virtues and ethical values. Negative role models are rarely used and if so,
      physicians are rather described as medical quacks in such fiction then exhibiting
      primarily a corrupted character. I suggest that a fictional story that presents
      exclusively a negative role model of a physician could also be a valuable,
      admittedly difficult, teaching resource to demonstrate the consequences of
      absolute loss of ethical standards and virtues in physicians. A not widely known
      example of this genre is Louis-Ferdinand Celine's (1894-1961) novel Voyage au
      bout de la nuit (Journey to the End of the Night), published in 1932. Having a
      strong autobiographical background, the novel described the adventures of the
      medicine student, Ferdinand Bardamu, during the first world war, in the African
      colonies as a trader, in the United States of America as factory worker, and
      later after finishing his education, as a doctor for the poor. Unfortunately, Dr
      Bardamu develops an unprofessional, even criminal behaviour, and may serve as a
      negative role model for the virtues of physicians. This article will familiarise
      the reader with the novel and its physician author.

PMID- 16461482
TI  - Neurophysiological and perceptual correlates of navigational impairment in
      Alzheimer's disease.
AB  - We assessed visual processing related to navigational impairment in Alzheimer's
      disease hypothesizing that visual motion evoked responses to optic flow
      simulating observer self-movement would be linked to navigational performance.
      Mild Alzheimer's disease and older adult control subjects underwent open-field
      navigational testing, visual motion perceptual threshold determination and a
      battery of neuropsychological examinations. We recorded visual motion evoked
      potentials (EPs) at occipital and parietal sites during centred visual fixation.
      Randomly moving or stationary pattern pre-stimuli preceded horizontal motion and
      radial optic flow stimuli to separate motion N200s from pattern onset responses.
      Radial optic flow evoked N200 responses comparable with those obtained with
      uniform horizontal motion, despite the variety of motion directions in radial
      optic flow. Alzheimer's disease patients showed smaller radial optic flow N200s
      than older adult subjects, and these were greatly diminished when preceded by
      stationary dots. Combining N200 amplitudes with optic flow perceptual thresholds
      and contrast sensitivities yielded a strong correlation with navigational
      impairment in Alzheimer's disease (R2 = 0.95). We conclude that navigational
      impairment in Alzheimer's disease is linked to a disorder of extrastriate visual
      cortical motion processing reflected in specific perceptual and
      neurophysiological measures.

PMID- 16461483
TI  - Current status of patient radiation doses from computed tomography examinations
      in Tanzania.
AB  - The aim of this study was to assess the magnitude of radiation dose imparted to
      patients undergoing CT (computed tomography) examinations in Tanzania. The
      effective doses to patients undergoing five common CT examinations were obtained
      from eight health centres. The doses to patients were estimated using
      measurements of CTDI, exposure-related parameters and the CTDOSE software based
      on NRPB conversion factors. The mean effective doses in Tanzania for CT
      examinations of head, lumbar spine, chest, abdomen and pelvis were 2.2+/-0.9,
      5.4+/-2.3, 12.2+/-3.4, 15.3+/-6.0 and 13.4+/-7.3 mSv, respectively. The mean
      effective doses and the variations in dose between hospitals in Tanzania were
      mostly comparable with reported values in the literature for six different
      countries from Europe. The observed wide variation in mean effective dose for
      similar CT examination among hospitals was largely influenced by different CT
      scanning protocols employed among hospitals. In view of the observed causes of
      variation in patient doses, it was concluded that further studies are needed to
      investigate the methods that can reduce dose to patients without affecting image
      quality.

PMID- 16461484
TI  - Mammographic breast cancer screening for women previously treated with high
      breast doses for diseases such as Hodgkin's.
AB  - In screening of a general population for breast cancer, benefit/risk ratios are
      of the order of 100/1. For the very small subgroup of women treated by
      radiotherapy for Hodgkin's disease below age 35, calculations of this type
      require different considerations, an overview of which is given in this text. It
      is concluded that although such previous exposures will increase their radiation
      risk, their increased risk of carrying an undetected breast cancer means that the
      potential benefit for them of screening is increased even more. In the United
      Kingdom, the Department of Health has recommended annual screening for these
      women.

PMID- 16461485
TI  - An assessment of digital stereotaxis in the National Health Service Breast
      Screening Programme.
AB  - A woman may be invited back for further assessment if an abnormality is found on
      her mammogram. A stereotactic attachment is used to determine where to place the
      biopsy device. Digital equipment has the advantage of providing images almost
      instantaneously and utilising software to determine the location of the sampling
      device. These devices should make the procedure quicker and hence less traumatic
      for the women. However, digital devices have poorer spatial and contrast
      resolution, which could adversely affect the accuracy of sampling device
      placement. Although the dose received during a normal screening mammogram is well
      known, the dose for the stereo procedure is unknown, partly because only a small
      part of the breast is directly irradiated. However, the lady may undergo multiple
      exposures. For a prospective survey of doses and technique arm of the study a
      proforma was completed for 134 women. The dose women received during a
      stereotactic procedure was estimated.

PMID- 16461486
TI  - Dose to cardiologists in haemodynamic and electrophysiology cardiac
      interventional procedures.
AB  - Interventional cardiac procedures can be complex and involve extensive use of low
      dose rate fluoroscopy and high dose rate in image acquisition mode; hence, staff
      may receive significant radiation exposure. Radiation exposure to operators was
      assessed in 173 procedures. Fluoroscopy time, number of acquired images and dose
      area product were recorded and occupational dose assessed with thermoluminescence
      dosemeters. The effective dose to the operator was compared with relevant
      literature data: values found were generally lower than those reported for other
      interventional cardiology laboratories. This is probably because of the strict
      radiation protection policy in our centre. Higher effective doses were found for
      defibrillator implantation and percutaneous transluminal coronary angiography
      procedures; for other cardiac procedures, effective dose was lower. Yearly
      extrapolated occupational doses to cardiologists are lower than the regulatory
      dose limit and in the lower band of doses reported in the literature.

PMID- 16461487
TI  - Investigation of occupational radiation exposure during interventional cardiac
      catheterisations performed via radial artery.
AB  - The purpose of this study was to determine the thyroid, sternum and hand
      radiation doses of radiologists who perform angiographies and angioplasties via
      the radial artery. Staff radiation dose was estimated for 21 cardiac
      interventional catheterisations. Thermoluminescence dosemeters (TLDs) were used
      to determine radiation dose for each procedure at the right and left wrist, at
      the sternum and the thyroid. A dose area product (DAP) meter was also attached to
      give a direct value in Gy cm2 for each procedure. Staff radiation doses varied
      between 34 and 235 microGy per procedure at the left wrist, 28 and 172 microGy at
      the right wrist, 16 and 106 microGy at the level of the thyroid and 16 and 154
      microGy at the level of the sternum. The DAP values varied between 25 and 167 Gy
      cm2. Radiation doses in this study are comparable to those reported in previous
      studies. Moreover, good correlation was found between the DAP values and the
      occupational dose measured with TLDs.

PMID- 16461488
TI  - Performance evaluation and testing of digital intra-oral radiographic systems.
AB  - Four digital intra-oral radiographic systems were tested and evaluated; three
      charge-coupled device (CCD) based systems from RVG, Visualix and Sidexis and a
      photostimulable phosphor (PSP) system from DenOptix. Image quality was assessed
      using three purpose-built phantoms to measure uniformity, low contrast detail
      detectability and signal-to-noise ratio (SNR). Limiting resolution was measured
      using a 20 lp mm(-1) bar pattern. Radiation output inaccuracies caused
      difficulties in achieving optimum doses for CCD systems. However, the accuracy
      was improved by using K-edge filters. SNR measurements proved to be a useful tool
      in assessing system performance. Each system has specific attributes: resolution
      was highest for the RVG system, the Visualix system measured the highest SNR and
      the lowest exposure settings were on the Sidexis system. Test methods and
      phantoms developed are suitable for acceptance testing and commissioning digital
      dental X-ray systems and for programming each system to produce an optimum level
      of image quality.

PMID- 16461489
TI  - Digital radiographic equipment in the Belgian dental office.
AB  - A survey was performed among Belgian dentists to evaluate the use and management
      of digital radiographic equipment. The majority of respondents work as general
      dental practitioners. One out of eight sets of equipment for extraoral exposures
      is digital. For intraoral radiography, 30% of the equipment is digital. While
      exposure time is reduced by about 50% for digital intraoral radiography compared
      with conventional radiography, no differences can be found between different
      conventional film speed classes. Appropriate collimation of the radiation beam is
      only sparingly used. Beam aiming devices to hold the film and position the
      radiation beam are not used by the majority of dentists. While 25% of the
      respondents stand behind a protective wall during exposure, 8% of dentists remain
      next to the patient during exposure while assisting in holding the film inside
      the mouth. A minority of the latter practitioners wear lead aprons.

PMID- 16461490
TI  - Entrances skin dose distribution maps for interventional neuroradiological
      procedures: a preliminary study.
AB  - Dose estimation in interventional neuroradiology can be useful to limit skin
      radiation injuries. The purpose of this study was to evaluate the role of
      entrance skin dose (ESD) maps in planning exposure condition optimisation.
      Thirteen cerebral angiography and five embolisation procedures were monitored,
      measuring ESD, dose-area product (DAP) and other operational parameters. A
      transmission ionisation chamber, simultaneously measuring air kerma and DAP,
      measured dose-related quantities. Data acquisition software collected dosimetric
      and geometrical data during the interventional procedure and provided a
      distribution map of ESD on a standard phantom digital image, with maximum value
      estimation. Values of 88-1710 mGy for maximum skin dose and 16.7-343 Gy cm2 for
      DAP were found. These data confirm the possibility of deterministic effects
      during therapeutic interventional neuroradiological procedures like cerebral
      embolisation. ESD maps are useful to retrospectively study the exposure
      characteristics of a procedure and plan patient exposure optimisation.

PMID- 16461491
TI  - Retrospective evaluation of occurrence of skin injuries in interventional cardiac
      procedures.
AB  - Interventional cardiology procedures can involve high doses to patients and, in
      particular, to patients' skin, the tissue at greatest risk of deterministic
      injuries. The evaluation of skin dose from interventional procedures is
      recommended, but difficult because of the amount of different X-ray fields and
      projections used in a procedure. For this reason, a retrospective follow-up study
      has been developed to identify skin injuries in patients submitted to one or more
      cardiac interventions in the Udine hospital between 1998 and 2002. Seventy-eight
      patients with a cumulative dose-area product >300 Gy cm2 were selected from 3332
      patients, who underwent 5039 procedures. In this group the maximum skin dose was
      6.7 Gy. The clinical follow-up, performed using the LENT-SOMA methodology, has
      not detected skin injuries and this result allows a frequency to be estimated for
      skin injuries in patients undergoing repeated cardiac procedures of <3 x 10(-4)
      in our centre.

PMID- 16461492
TI  - Patient skin dosimetry in haemodynamic and electrophysiology interventional
      cardiology.
AB  - With the increase in number and complexity of interventional cardiology (IC)
      procedures, it is important to monitor skin dose in order to decrease skin
      injuries. This study investigated radiation doses for patients undergoing IC
      procedures, compare results with the literature and define a local dose-area
      product trigger level for operators to identify situations likely to exceed the
      threshold for transient skin erythema of 2 Gy. Dosimetric data were collected for
      77 haemodynamic and 90 electrophysiological procedures. Mean maximum local skin
      doses (MSDs) were 0.28 Gy for coronary angiography, 1.03 Gy for percutaneous
      transluminal coronary angioplasty (PTCA), 0.03 Gy for pacemaker insertion, 0.17
      Gy for radiofrequency ablation for nodal tachycardia, 0.10 Gy for WPW and 0.22 Gy
      for atrial flutter. Since MSD values for the other procedures were well below the
      deterministic effect limit, a trigger level of 140 Gy cm2 was derived for PTCA
      procedures alone.

PMID- 16461493
TI  - Radiation dose levels during interventional cardiology procedures in a tertiary
      care hospital.
AB  - The aim of our investigation was to prospectively measure the patient radiation
      exposure from different cardiological procedures performed in the Catheterisation
      laboratory of the University Hospital Gasthuisberg in Leuven. The following local
      reference values were proposed: 40, 47 and 80 Gycm2 for coronary angiography (CA)
      or angioplasty (PTCA and stent implantation for elective patients), radio
      frequency ablation with angiographic images and CA plus ad hoc PTCA,
      respectively.

PMID- 16461494
TI  - Dose conversion coefficients for interventional procedures.
AB  - Effective dose (E) is a convenient quantity to estimate the stochastic risk of
      radiation applied to patients in interventional procedures and can be used for
      optimisation. Relatively long exposure times may cause deterministic effects.
      Hence it is necessary to know the (maximum local) doses in organs owing to the
      interventional procedure. In practice, organ doses cannot be measured directly.
      They are derived by applying a conversion coefficient to a measurable quantity,
      e.g. dose-area product (DAP) or entrance skin dose. For a number of
      interventional procedures, dose conversion coefficients (DCCs) can be found in
      the literature. Various DCCs are stated for nominally equal procedures, e.g. for
      percutaneous transluminal coronary angioplasty both 0.18 and 0.27 mSv Gy(-1) cm(
      2) were reported to convert DAP to effective dose. Dependence of DCC on protocol
      and equipment parameters, as demonstrated through Monte Carlo simulation in this
      paper, makes it hazardous to simply adopt a literature value.

PMID- 16461495
TI  - The influence of patient size on patient doses in cardiology.
AB  - In cardiology and interventional radiology, areas that contribute large
      components to medical radiation exposure, a major source of variation in patient
      dose is the variation in complexity between cases for nominally identical
      procedures. In patient dose surveys, this variation tends to mask that due to
      patient size. The effect of applying a previously defined size correction to
      cardiology patient dose-area product (DAP) records was investigated. The
      correction method uses the experimentally determined relationship between patient
      diameter and DAP to derive a factor to convert DAP to that which would be
      expected had the patient been similar in size to ICRP Reference Man. The size
      correction was found to greatly reduce the residual correlation of DAP with
      patient weight. An implication of this finding is that data collection for the
      setting of diagnostic reference levels in cardiology can be performed for all
      patients rather than just 'standard-sized' patients.

PMID- 16461496
TI  - Patient dosimetry approaches in interventional cardiology and literature dose
      data review.
AB  - Interventional radiology contributes a significant proportion of the collective
      dose of the population from medical exposures. Interventional radiology
      procedures are usually fluoroscopy-guided diagnostic and therapeutic
      interventions. When complex procedures are performed or procedures are repeated
      for the same patient, high-radiation dose levels can occur because procedures
      often require long fluoroscopy times and require high-quality images. For all of
      these reasons, dosimetric evaluations in interventional radiology are widely
      increasing. Patient dosimetry methods currently used in interventional radiology
      may be divided into three categories according to dosimetry purpose: (I)
      dosimetry for stochastic risk evaluation, (II) dosimetry for quality assurance
      and (III) dosimetry to prevent the deterministic effects of radiation. A short
      description of dosimetric methods used in interventional cardiology practice and
      relevant published dosimetric data are reported.

PMID- 16461497
TI  - Image quality criteria in cardiology.
AB  - Image quality evaluation plays a key role in the process of optimisation in
      radiological procedures. Image quality criteria for cardiac cine-angiography were
      recently agreed as part of a European Research Project, and a scoring system
      based on these criteria has been developed to allow an 'objective' measurement of
      the quality of cardiac angiograms. Two studies aimed at the evaluation of the
      methodology have been completed, demonstrating that the method can be applied to
      cardiac images and translated into a scoring system that yields reproducible
      data. Based on the results of these studies, quality criteria have been further
      reviewed by DIMOND III panel and the updated version is presented in this paper.

PMID- 16461498
TI  - Radiation dose vs. image quality for low-dose CT protocols of the head for
      maxillofacial surgery and oral implant planning.
AB  - The goal of this study was to determine the acquisition parameters for a low-dose
      multi-slice CT protocol and to compare the effective dose and the image quality
      of this low-dose protocol with the image quality of a clinical multi-slice CT
      protocol, routinely used for visualisation of the head. The low-dose protocol was
      derived from a clinical multi-slice CT protocol by lowering mA s and kV and
      increasing the pitch. The low-dose protocol yielded a dose reduction from 1.5 to
      0.18 mSv for a multi-slice CT scan of the whole head, whereas noise in the low
      dose CT images was increased. For bone segmentation, noise could be reduced by
      use of a non-linear edge preserving smoothing filter. Tests on ESP and skull
      phantom indicated that the accuracy of the measurements on low-dose CT is
      acceptable for image-based planning of maxillofacial and oral implant surgery,
      reducing the dose by a factor of 8.

PMID- 16461499
TI  - Analysis of image quality in digital chest imaging.
AB  - An evaluation of the image quality of an amorphous silicon flat-panel detector
      system and a computed radiology system compared with a screen-film system was
      performed by means of contrast-detail phantom images. Hard and soft copy images
      were evaluated. Although patient dose at clinical settings was strongly decreased
      with the amorphous silicon system, the low-contrast visibility with this system
      was still significantly better than with the screen-film system. For the computed
      radiology system, low-contrast visibility was comparable to the screen-film
      system. Best results were obtained by soft copy reading at full resolution with
      adaptation of contrast and brightness. Changing tube voltage (102-133 kV), or
      additional filtration, did not significantly affect image quality. However, low
      contrast visibility improved significantly with increasing exposure. It was
      clearly demonstrated that, in chest imaging, the amorphous silicon system has
      superior imaging characteristics compared to the screen-film and the computed
      radiology system.

PMID- 16461500
TI  - Comparison of a CCD and a flat-panel digital system in an Interventional
      Cardiology Laboratory.
AB  - We evaluated the performances of angiographic units equipped with a flat-panel
      (FP) detector and image intensifier (II) charge-coupled device (CCD) in the
      Interventional Cardiology (IC) Department. Entrance dose rate and dose per image,
      along with the dose at the II level were measured using 2 mm copper sheets to
      simulate a patient. Image quality (IQ) was evaluated using a phantom. Doses
      increased with fluoroscopy level changing from low to high. FP presented higher
      doses than CCD. Periodic measurements showed differences of up to 35%. Low mode
      IQ did not significantly differ from normal and high mode for both systems. Low
      fluoroscopy mode was decided to be used routinely. Both X-ray systems performed
      within international recommendations for conventional systems with the exception
      of higher cine radiation doses and II dose rates, stressing the fact that more
      studies are required to investigate whether dose levels should be adjusted.

PMID- 16461501
TI  - Quantification of motion unsharpness in digital fluoroscopy.
AB  - The objectives of this work were first to develop a convenient method to quantify
      persistence in digital fluoroscopy systems, then to quantify the effect of
      variable temporal averaging on the detection of moving low-contrast test details
      within digital fluoroscopic and pulsed fluoroscopic images. The results were
      analysed to clarify the relationship between the optimum persistence required to
      see the lowest contrast for circular test details for a range of diameters and
      their speed of movement. The optimum persistence values obtained are compared
      with the limited data available on speeds of movement of patient organs during
      fluoroscopy. It is tentatively concluded that for imaging the abdomen, the
      optimum imaging system persistence time constant is approximately 0.15 s. For the
      much greater speeds associated with cardiac motion, no additional frame averaging
      is necessary, i.e. just the persistence provided by the observer's visual system
      appears to be optimal for small objects.

PMID- 16461502
TI  - Pilot study into optimisation of viewing conditions for electronically displayed
      images.
AB  - The increased use of soft-copy reporting introduces new concerns over the effect
      of viewing conditions on the observer's ability to report images. Owing to their
      lower luminance, electronic display screens may be more susceptible to poor
      viewing conditions than conventional viewing boxes and there is the potential for
      images to be displayed in locations not optimised for viewing radiographs. In the
      present work, the effects of sub-optimal viewing conditions on the observer's
      performance for images on an electronic display device are investigated. A test
      object was used to produce a computed radiography image containing a wide range
      of grey levels. The image was scored under quasi-ideal and sub-optimal conditions
      and the effect of changing the viewing conditions on the observer's performance
      determined. Basic photometric quantities were used to characterise the viewing
      conditions and the degradation in observer performance related to these
      quantities. The presence of structured reflection had a significant effect on the
      observer's ability to discern low-contrast objects. The study demonstrates the
      need for adequate viewing conditions especially when images are displayed on low
      luminance devices in sub-optimal conditions.

PMID- 16461503
TI  - AEC set-up optimisation with computed radiography imaging.
AB  - Phototimer set-up is a critical procedure for dose and image quality optimisation
      in computed radiography (CR) systems. While a conventional radiography automatic
      exposure control device (AEC) can be calibrated in order to gain a constant
      optical density on the film independent of beam quality and patient size, CR
      detectors present a high dynamic range which allows a much larger dose interval,
      but with different image quality levels. CR leads to a less frequent exam
      repetition, but may produce quite noisy images if the exposure level on the plate
      is not correct. The aim of this work is to evaluate the performance of a CR plate
      (Agfa MD40) in order to optimally calibrate an AEC device. The plate response has
      been characterised in terms of digital signal, exposure on the plate and signal
      to-noise ratio for different beam qualities, in a patient of standard size.

PMID- 16461504
TI  - Commissioning and quality assurance protocol for dual energy X-ray absorptiometry
      (DEXA) systems.
AB  - This study reports on the development and evaluation of a protocol for testing
      DEXA systems, which can be incorporated into a routine medical
      physics/engineering service. Methodologies are reported for (1) scatter
      measurement, (2) estimation of reference dose and (3) enquiry into potential
      sources of overexposure. Results show that fan-beam and cone-beam systems require
      shielding if the walls or operator are within 1 m of the table. Patient reference
      dose was estimated using the dose-area product (DAP). This varied over an order
      of magnitude from 2 to 36 mGy cm2 in the range of systems studied. The inquiry
      into potential sources of overexposure revealed some weaknesses in current
      practise including a design which prevents the inclusion of DAP metres; beam non
      uniformity; incorrect specification of patient dose and the risk of overexposure
      when tube operates during patient positioning.

PMID- 16461505
TI  - Radiation protection and safety in medical use of ionising radiation in Republic
      of Bulgaria--harmonization of the national legislation with Euratom directives.
AB  - From February 2002 to November 2003 the National Centre of Radiobiology and
      Radiation Protection conducted a PHARE twinning project 'Radiation Protection and
      Safety at Medical Use of Ionising Radiation'. The main purposes of the project
      were the harmonization of Bulgarian legislation in the field of radiation
      protection with EC Directives 96/29 and 97/43 Euratom, and the establishment of
      appropriate institutional infrastructure and administrative framework for their
      implementation. This paper presents the main results of the project: elaboration
      of Ordinance for Protection of Individuals from Medical Exposure; performance of
      a national survey of distribution of patient doses in diagnostic radiology and of
      administered activities in nuclear medicine and establishment of national
      reference levels for the most common diagnostic procedures.

PMID- 16461506
TI  - On the use of DICOM cine header information for optimisation: results from the
      2002 European DIMOND cardiology survey.
AB  - The paper explores the level of information contained within the DICOM header in
      images from various cardiology systems. Data were obtained in the European DIMOND
      survey on image quality (Italy, Ireland, Belgium, Greece and Spain). Images from
      five standard diagnostic cardiology procedures carried out in six European
      hospitals have been analysed. DICOM header information was extracted to a
      database in order to analyse how it could help in the optimisation of the
      procedures. The level of data contained in the headers differs widely between
      cardiology systems. None of the X-ray systems in the 2002 survey archives the
      dosimetric data in the DICOM header. The mean number of runs per procedure ranges
      between 7.5 and 15.4 and the mean number of frames per procedure between 575 and
      1417. Differences in kVp, mA, pulse time, distances and C-arm angulations are
      substantial and suggest that there exists a wide range for optimisation.

PMID- 16461507
TI  - Data analysis from a multi-centre, comparative study of angiographic examinations
      leading to practical guidelines for the optimisation of patient doses.
AB  - In this study, patient doses were analysed against exposure parameters and
      procedure protocol. Patient doses were measured in seven hospitals for a standard
      diagnostic vascular examination. Image quality was assessed using the contrast
      detail phantom from Nijmegen (CD-DISC 2.0). A link between dose and image quality
      was investigated. Image quality strongly depends on the preset dose level. The
      higher the dose level, the better the image quality, but also the higher the
      patient dose. However, no clear correlation was found between total dose-area
      product (DAP) or effective dose and image quality. A large range in patient dose
      was found: DAP (22-130 Gy cm2) and effective dose (3.9-16.8 mSv). A difference in
      number of frames was also found in the different centres, owing to different
      frame rates (3-2-1 frames per second) and use of oblique projections. Differences
      in doses and exposure settings offer the possibility of optimising patient doses
      in angiography and interventional radiology.

PMID- 16461508
TI  - Equipment standards for interventional cardiology.
AB  - Interventional radiology has seen rapid growth in cardiology and represents an
      alternative to hazardous surgery. Recently there has been a substantial growth in
      the number of procedures being performed and interventional cardiology (IC)
      procedures are the most common interventional procedures in Europe. Advances in
      imaging technology have facilitated the development of increasingly complex
      radiological IC equipment. Currently, the technology is developing at a rate
      ahead of supporting research, equipment standards and a regulatory framework.
      International standards play a key role in the design, manufacture and
      performance of radiological IC equipment. A survey of 12 IC systems (15 imaging
      chains) was conducted in Irish hospitals. The aim of the study was to assess the
      imbalance between rapidly advancing technology and existing standards and to
      propose recommendations for new IC equipment standards. The results demonstrate
      the need for definitive equipment requirements and standardisation in the design,
      manufacture, acceptance and maintenance of IC equipment.

PMID- 16461509
TI  - Patient and staff doses in radiology and cardiology in Estonia.
AB  - This paper presents a short description of the Estonian radiological facilities
      and the doses to staff in radiology and cardiology. For each major work practice,
      the annual (2002) average effective doses are listed: X-ray diagnostics
      (radiologists: 1.11 mSv; radiographers: 1.03 mSv), interventional radiology
      (doctors in cardioangiography: 6.04 mSv; radiologist in angiography: 2.71 mSv),
      nuclear medicine (radiologists: 0.91 mSv; technicians: 2.41 mSv) and radiotherapy
      (radiologists: 1.00 mSv; technicians: 1.04 mSv). This paper also presents the
      first results of adult patient dose measurements in diagnostic X-ray departments
      in Estonia. The average entrance skin dose for chest PA examinations was 0.3 mGy,
      for chest LAT 0.9 mGy, for lumbar spine AP 6.4 mGy, for lumbar spine LAT 10.7 mGy
      and for pelvis AP 3.9 mGy.

PMID- 16461510
TI  - Protocols for dosimetry and patient reference levels.
AB  - Doses in radiology should be as low as reasonably achievable. In order to compare
      practice in different centres it is necessary to compare patient doses. This can
      only be undertaken if dosimetry studies are similar. In order to facilitate
      comparisons, the DIMOND consortium developed a patient dosimetry protocol.
      Reference doses have been proposed to identify centres where optimisation studies
      would be of benefit. Whilst reference doses have been established for common
      radiographic and fluoroscopic examinations, little research has been undertaken
      in the area of digital radiology, partly owing to the rapid technological changes
      occurring in digital and interventional radiology. Dosimetry data obtained by the
      DIMOND research project were compared with data from published literature. Data
      for various digital and interventional radiology procedures were reviewed.
      Proposals are made for reference doses. There is obviously a need for
      standardised approaches to patient dosimetry, which should be recorded in the
      hospital's information system.

PMID- 16461511
TI  - The DIMOND project and its impact on radiation protection.
AB  - The DIMOND III project comprised work packages and subprojects to research
      digital imaging, interventional radiology and interventional cardiology, i.e.
      areas where there has been rapid technological change, not matched by radiation
      protection research. Whilst new practices have great potential benefit, there are
      risks to patients and staff if the technology is implemented inappropriately.
      DIMOND aimed to develop generic technology assessment and optimisation tools.
      Clinical quality criteria and technical parameters were included so that digital
      imaging procedures can be introduced appropriately. Frequency and dimensions of
      acceptance and constancy testing for digital imaging systems were studied, along
      with differences between objective measures of image quality and subjective
      indices. Patient dosimetry was performed to propose and to establish reference
      values. Clinical evaluation projects included cardiology, interventional
      radiology and digital mammography. As a result of the DIMOND project, quality
      criteria for several procedures were developed. Example results are presented in
      this paper.

PMID- 16461512
TI  - Fluence-to-absorbed dose conversion coefficients for use in radiological
      protection of embryo and foetus against external exposure to protons from 100 MeV
      to 100 GeV.
AB  - In the literature, no conversion coefficients are available for use in
      radiological protection of embryo and foetus against external exposure to
      protons. This study used the Monte Carlo code MCNPX to determine mean absorbed
      doses to the embryo and foetus when the mother is exposed to proton fields.
      Monoenergetic protons ranging from 100 MeV to 100 GeV were considered. The
      irradiation geometries include antero-posterior (AP), postero-anterior (PA),
      lateral (LAT), rotational (ROT) and isotropic (ISO). At each of these standard
      irradiation geometries, absorbed doses to the foetal brain and body were
      calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months. Proton
      fluence-to-absorbed dose conversion coefficients were derived for the four
      prenatal ages.

PMID- 16461513
TI  - Proton radiography applications with MCNP5.
AB  - A modified version of MCNP5 has been developed to treat continuous-energy proton
      transport. This work is summarised in companion papers by Hughes et al. and Bull
      et al. (in these proceedings). An intrinsic part of this development effort has
      involved testing, verification and validation of a capability for simulating
      proton radiographs. This paper presents the results of calculations simulating
      various different test objects and the effects of alternative physics models. The
      significant physics processes include elastic scattering, multiple coulomb
      scattering, collisional energy-loss and straggling, magnetic fields and
      attenuation owing to nuclear interactions. Comparisons with experimental data are
      presented.

PMID- 16461514
TI  - Radiation doses to patients from digital subtraction angiography.
AB  - This investigation determined patient doses during digital subtraction
      angiography (DSA). Fluoroscopy time, dose-area product (DAP) and entrance surface
      air kerma (ESAK) were analysed from 263 DSA examinations, classified into seven
      categories: (1) abdominal aorta, iliac, femoral, popliteal and leg arteries; (2)
      abdominal aorta and superselective DSA of renal arteries; (3) combination of (1)
      and (2); (4) superselective DSA of common carotid and vertebral arteries,
      intracranial branches in face and profile projections; (5) superselective DSA of
      hepatic, splenic, superior and inferior mesenteric arteries; (6) combination of
      (1) and (4); and (7) celiac trunk and branches. Median DAP values were 67.7,
      92.9, 76.6, 53.6, 105.7, 76.1 and 2.6 Gy cm2, respectively. With the exception of
      one examination, ESAK values were below 2 Gy: the limit for erythema. Compared
      with published data, DAP values were within the range reported for (1) and (4),
      slightly larger for (2) and (5), whereas no references were identified for the
      remaining three categories.

PMID- 16461515
TI  - Entrance radiation doses during paediatric cardiac catheterisations performed for
      diagnosis or the treatment of congenital heart disease.
AB  - The purpose of this study was to estimate the radiation exposure of children,
      during cardiac catheterisations for the diagnosis or treatment of congenital
      heart disease. Radiation doses were estimated for 45 children aged from 1 d to 13
      y old. Thermoluminescent dosemeters (TLDs) were used to estimate the posterior
      entrance dose (DP), the lateral entrance dose (DLAT), the thyroid dose and the
      gonads dose. A dose-area product (DAP) meter was also attached externally to the
      tube of the angiographic system and gave a direct value in mGy cm2 for each
      procedure. Posterior and lateral entrance dose values during cardiac
      catheterisations ranged from 1 to 197 mGy and from 1.1 to 250.3 mGy,
      respectively. Radiation exposure to the thyroid and the gonads ranged from 0.3 to
      8.4 mGy to 0.1 and 0.7 mGy, respectively. Finally, the DAP meter values ranged
      between 360 and 33,200 mGy cm2. Radiation doses measured in this study are
      comparable with those reported to previous studies. Moreover, strong correlation
      was found between the DAP values and the entrance radiation dose measured with
      TLDs.

PMID- 16461516
TI  - Are new technologies always reducing patient doses in cardiac procedures?
AB  - Dynamic digital flat-panel (FD) imaging technology is characterised by a higher
      sensitivity and image quality compared to image intensifier (II) technology. In
      this study, an angiography system based on II and one based on FD were compared
      with respect to system performance and impact of patient dose in interventional
      cardiology. When entrance surface air kerma rates are measured, the FD system
      requires a reduced dose rate, of up to 40%. For coronary angiography (CA),
      fluoroscopy time (FT) and dose-area product (DAP) were 4.3 +/- 5.0 min and 31.2
      +/- 30.2 Gy cm2 on the II system and 4.4 +/- 3.8 min and 33.4 +/- 19.2 Gy cm2
      with the FD system. For percutaneous transluminal coronary angiography, FT and
      DAP were 11.4 +/- 10.7 min and 52.1 +/- 45.0 Gy cm2 on II and 10.7 +/- 8.7 min
      and 66.9 +/- 54.4 Gy cm2 on DF. Data comparison suggests that reduced entrance
      dose rates do not automatically imply a reduction of patient dose in clinical
      practice.

PMID- 16461517
TI  - Development and application of programs to measure modulation transfer function,
      noise power spectrum and detective quantum efficiency.
AB  - This project aimed to produce programs to calculate the modulation transfer
      function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE)
      of digital X-ray systems, given a suitable digital image. The MTF was calculated
      using the edge technique and the NPS was calculated from a flat field image. Both
      programs require a suitably edited DICOM image as input. The DQE was then
      calculated from the output of MTF and NPS programs. This required data external
      to the DQE program to estimate the number of quanta per mm2 in the beam which
      formed the NPS image. All three programs run independent of each other on a PC
      and require no special software to be installed. Results for MTF, NPS and DQE for
      a Philips AC3 CR system are presented. In addition, the results for MTF from a
      Siemens Duo CT scanner with a specially designed PTFE edge are also shown.

PMID- 16461518
TI  - Quality control of equipment used in digital and interventional radiology.
AB  - Digital and interventional radiology are increasingly important areas of
      radiology. Quality control (QC) of such equipment is of particular importance to
      avoid unnecessary high doses and to help to achieve good image quality. Within
      the DIMOND III project, equipment requirements and specifications for digital and
      interventional radiology have been formulated. A protocol for QC tests has been
      drafted based on various national and international recommendations. Tests are
      included for various parts of the imaging chain, i.e. X-ray tube and generator, X
      ray tube control system, laser printer and display station, and image quality and
      patient dose. Preliminary tolerance levels have been set for the various tests,
      after initial measurements. To check the suitability of QC tests and stated
      tolerance levels, measurements were made at the University Hospital Gasthuisberg
      in Leuven for equipment used for paediatric radiology and a unit used for chest
      examinations. The results of the various tests are reported.

PMID- 16461519
TI  - Patient dosimetry in diagnostic and interventional radiology: a practical
      approach using trigger levels.
AB  - Patient dosimetry is performed in radiology and interventional radiology to
      assess whether deterministic injuries may occur and to establish the risk of
      stochastic effects. A fundamental problem for patient dosimetry is that no single
      quantity can be used to accurately assess both the risk of stochastic effects and
      whether deterministic injuries will occur following a specific examination or
      procedure. In cardiology and interventional radiology, two different approaches
      to patient dosimetry are commonly used. Effective dose is a quantity which
      correlates reasonably well with the risk of stochastic effects. Effective dose
      may be deduced from the dose-area product (DAP) for the procedure if sufficient
      information is known. DAP does not correlate with maximum skin dose, which may be
      used to predict whether deterministic injuries may occur. DAP meter readings may
      be used as a trigger level for the investigation of maximum skin entrance dose.
      Trigger levels for different procedures are proposed.

PMID- 16461520
TI  - Current challenges of full field digital mammography.
AB  - Full field digital mammography (FFDM) has advantages over screen-film mammography
      (SFM), but some important challenges remain. The first challenge is related to
      the specific characteristics of FFDM. It remains unclear, which shape and
      limiting values of the modulation transfer function have the most influence on
      the performance of a detector, such as the effect of the image display on the
      overall image quality and the effect of processing on cancer detection. In order
      to assess the image quality of FFDM, we have set up a scoring system. The second
      challenge is related to screening mammography: is the quality of an image the
      same when it is viewed on different monitors and with different processing
      algorithms? Is Computer Aided Diagnosis necessary in a screening environment? In
      FFDM, the effect of different detectors, processing and display possibilities on
      the image and on cancer detection are not clearly investigated.

PMID- 16461521
TI  - Image quality and dose management in digital radiography: a new paradigm for
      optimisation.
AB  - The advent of digital imaging in radiology, combined with the explosive growth of
      technology, has dramatically improved imaging techniques. This has led to the
      expansion of diagnostic capabilities, both in terms of the number of procedures
      and their scope. Throughout the world, film/screen radiography systems are being
      rapidly replaced with digital systems. Many progressive medical institutions have
      acquired, or are considering the purchase of computed radiography systems with
      storage phosphor plates or direct digital radiography systems with flat panel
      detectors. However, unknown to some users, these devices offer a new paradigm of
      opportunity and challenges. Images can be obtained at a lower dose owing to the
      higher detective quantum efficiency (DQE). These fundamental differences in
      comparison to conventional film/screens necessitate the development of new
      strategies for dose and quality optimizations. A set of referral criteria based
      upon three dose levels is proposed.

PMID- 16461522
TI  - Dose optimisation in computed radiography.
AB  - After the installation of computed radiography (CR) systems in three hospitals in
      Luxembourg a patient dose survey was carried out for three radiographic
      examinations, thorax, pelvis and lumbar spine. It was found that the patient
      doses had changed in comparison with the patient doses measured for conventional
      radiography in the same three hospitals. A close collaboration between the
      manufacturers of the X-ray installations, the CR imaging systems and the medical
      physicists led to the discovery that the speed class with which each radiographic
      examination was to be performed, had been ignored, during installation of the
      digital imaging systems. A number of procedures were carried out in order to
      calibrate and program the X-ray installations in conjunction with the CR systems.
      Following this optimisation procedure, a new patient dose survey was carried out
      for the three radiographic examinations. It was found that patient doses for the
      three hospitals were reduced.

PMID- 16461523
TI  - Patient dosimetry measurements in 50 radiology departments in Belgium.
AB  - Since July 2001, the Belgian law requires a yearly quality control measurement on
      all medical radiological equipment. The medical physicists of the AV Controlatom
      are certified experts in Belgium and perform these quality control measurements,
      including a patient dosimetry study. In this study, patient dosimetry results
      since January 2002 are presented for the following examinations: chest PA and
      LAT, abdomen and pelvis. Since conventional film-based imaging is currently being
      replaced by phosphorplate technology, a comparison between both technologies is
      made. In some radiology departments, digital imaging is already in use. These
      dosimetry results are also analysed. Dose reductions of >70% can be achieved. For
      the chest examinations, several departments still use fluoroscopy for positioning
      the patient. Results show that about half of the patient dose is due to the
      fluoroscopy. A comparison between the dose results and the European Diagnostic
      Reference Levels (EDRL) is made.

PMID- 16461524
TI  - Patient and staff doses in interventional neuroradiology.
AB  - Radiation doses for interventional examinations are generally high and therefore
      necessitate dose monitoring for patients and staff. Relating the staff dose to a
      patient dose index, such as dose-area product (DAP), could be quite useful for
      dose comparisons. In this study, DAP and skin doses of 57 patients, who underwent
      neurointerventional examinations, were measured simultaneously with staff doses.
      Although skin doses were comparable with the literature data, higher DAP values
      of 215 and 188.6 Gy cm2 were measured for the therapeutical cerebral and carotid
      examinations, respectively, owing to the use of biplane system and complexity of
      the procedure. Mean staff doses for eye, finger and thyroid were measured as
      80.6, 77.6 and 28.8 microGy per procedure. The mean effective dose per procedure
      for the radiologists was 32 microSv. In order to allow better comparisons to be
      made, DAP normalised doses were also presented.

PMID- 16461525
TI  - Implementation of QA and QC standards in radiology in Slovakia.
AB  - The Slovak government organizes the radiation protection policy through its
      regulatory authorities within the Ministry of Health, on a central level. The
      health protection regulations are compatible with international standards and
      recommendations of the ICRP and the EC. The general requirements on quality
      assurance (QA) and quality control (QC) (acceptance, constancy and routine
      tests), the guidance levels for various types of radiological examinations and
      the instructions for optimisation procedures are supported by Slovak technical
      standards, compatible with European standards. But the QA/QC process, as well as
      the training of the staff, needs improvement. The Slovak Medical University
      participates in the QA implementation through organising and managing national
      audits for control of the QA programme. In this paper, we present results of
      patient dose measurement studies carried out in the Slovak Republic, in the
      framework of activities of the Slovak Commission of QA established by the Slovak
      Ministry of Health.

PMID- 16461526
TI  - Investigation of possible methods for equipment self-tests in digital radiology.
AB  - Quality control in digital radiology can be time-consuming. Equipment self-tests
      may significantly decrease staff workload. The two most essential parameters for
      radiology systems are image quality and patient dose. Concerning patient dose,
      information on the dose-area product (DAP) values generally forms the basis for
      assessment of patient dose. DAP-values can be measured using a transmission
      ionisation chamber or calculated from equipment settings. In the present study,
      various image quality parameters were derived using a contrast-detail (C-D)
      phantom. The investigation included a computer-aided assessment of C-D images,
      which produced various parameters, and also parameters based upon scoring by
      human observers. In addition, another parameter was calculated from modulation
      transfer function (MTF) measurements. The automatically calculated parameters
      showed good correlation with human readings, although the number of X-ray systems
      studied is still limited. We propose a combined evaluation of DAP and
      automatically calculated C-D or MTF parameters for equipment self-tests.

PMID- 16461527
TI  - Reference levels in PTCA as a function of procedure complexity.
AB  - The multicentre assessment of a procedure complexity index (CI) for the
      introduction of reference levels (RLs) in percutaneous transluminal coronary
      angioplasties (PTCA) is presented here. PTCAs were investigated based on
      methodology proposed by Bernardi et al. Multiple linear stepwise regression
      analysis, including clinical, anatomical and technical factors, was performed to
      obtain fluoroscopy time predictors. Based on these regression coefficients, a
      scoring system was defined and CI obtained. CI was used to classify dose values
      into three groups: low, medium and high complexity procedures, since there was
      good correlation (r = 0.41; P < 0.001) between dose-area product (DAP) and CI. CI
      groups were determined by an ANOVA test, and the resulting DAP and fluoroscopy
      time third quartiles suggested as preliminary RLs in PTCA, as a function of
      procedure complexity. PTCA preliminary RLs for DAP are 54, 76 and 127 Gy cm2, and
      12, 20 and 27 min for fluoroscopy time, for the three CI groups.

PMID- 16461528
TI  - Optimisation strategies and justification: an example in uterine artery
      embolisation for fibroids.
AB  - Radiation risk has to be justified and optimised. This study discusses the
      radiation risk of uterine artery embolisation (UAE) for the treatment of
      fibroids. A total of 70 consecutive UAE dosimetry parameters were assessed. Using
      Monte Carlo simulation, organ and effective doses and dose conversion
      coefficients (DCCs) (mSv Gy cm(-2)) were calculated. During UAE optimisation,
      avoidance of oblique views and use of last-image-hold (LIH) documentation instead
      of digital subtraction angiography (DSA) were investigated. Mean dose-area
      product (DAP) was 37.1 Gy cm2 (median 23.7 Gy cm2) and mean fluoroscopy time was
      18.4 min (median 16.6 min). Dose values decreased as the study progressed: mean
      DAP for patients 1-21, 68.5 Gy cm2; patients 22-43, 35.7 Gy cm2; and patients 44
      69, 13.0 Gy cm2. Average DCC for DSA image procedures was 0.572, yielding a mean
      effective dose of 29.6 mSv (median 17.1 mSv). For LIH-only procedures, an average
      DCC of 0.813 was estimated [using mean effective dose: 10.6 mSv (median 8.1
      mSv)].

PMID- 16461529
TI  - Patient dosimetry and image quality in digital radiology from online audit of the
      X-ray system.
AB  - The present work describes an online patient dosimetry and an image quality
      system in digital radiology. For the patient dosimetry audit, current mean values
      of entrance surface dose (ESD) were compared with local and national reference
      values (RVs) for the specific examination type evaluated. Mean values exceeding
      the RV trigger an alarm signal and then an evaluation of the technical
      parameters, operational practice and image quality was begun, using data
      available in the DICOM header to derive any abnormal settings or performance to
      obtain the image. The X-ray tube output for different kVp values is measured
      periodically, to allow for the automatic calculation of ESD. The system allows
      also for image audit, linking the dose imparted, the image quality and the alarm
      condition, if produced. Results and the benefits derived from this online quality
      control are discussed here.

PMID- 16461530
TI  - Evaluation of risk of deterministic effects in fluoroscopically guided
      procedures.
AB  - A methodology for the evaluation of skin dose distribution and possible skin
      injuries on patients undergoing interventional procedures has been developed as
      part of the European DIMOND programme. Relevant dosimetric data from the
      procedures are recorded and other specific measurements for skin dose evaluation
      (slow films for therapy, radiochromic films, thermoluminescence dosemeters and
      optically stimulated luminescence dosemeters) have been carried out. For non
      cardiac and for some cardiac procedures, dose-area product values of 200 and 300
      Gy cm2 were proposed, respectively, as a trigger level for further detailed skin
      dose investigation and possible clinical follow-up. Results from a survey of 191
      selected complex procedures are reported. Out of all the patients included in the
      trial, 16% received skin doses > or =1.5 Gy. No skin injuries were found in any
      of the patients followed.

PMID- 16461531
TI  - Image quality measurements and metrics in full field digital mammography: an
      overview.
AB  - This paper gives an overview of test procedures developed to assess the
      performance of full field digital mammography systems. We make a distinction
      between tests of the individual components of the imaging chain and global system
      tests. Most tests are not yet fully standardised. Where possible, we illustrate
      the test methodologies on a selenium flat-panel system.

PMID- 16461532
TI  - Performance of the K-edge digital subtraction angiography imaging system at the
      European synchrotron radiation facility.
AB  - In this work we have characterised the K-edge digital subtraction angiography
      imaging system at the European Synchrotron Radiation Facility (ESRF, Grenoble,
      France). With this technique, after the minimally invasive intravenous injection
      of a contrast agent (iodine), two images are recorded simultaneously using
      monochromatic beams with energies bracketing the iodine K-edge. The image
      receptor consists of a two-line 432-pixel germanium detector. The logarithmic
      subtraction of the image set produced results in an iodine-enhanced image, where
      vessels are clearly visualised and contrast agent concentration can be precisely
      quantified. We have studied the imaging system in terms of the modulation
      transfer function, which was measured at the patient position, the 2-D normalised
      noise power spectrum, calculated for both raw and processed data, and the
      frequency-dependent detective quantum efficiency, which was calculated directly
      for final images. In addition, images of cylindrical phantoms with different
      concentrations of iodine, were also acquired.

PMID- 16461533
TI  - The application of image quality measurements for digital angiography.
AB  - The image quality (IQ) evaluation of a charge-coupled device (CCD)-based digital
      angiography system was assessed with respect to modulation transfer function and
      noise power spectrum. These values were used to calculate the system's frequency
      dependent detective quantum efficiency (DQE). The X-ray image detector was an
      image intensifier (II) lens coupled to a CCD camera. Two measurement setups were
      used. Setup A is standard IQ assessment, while Setup B more closely represented
      clinical conditions (polymethyl methacrylate (PMMA) of varying thickness placed
      between the X-ray tube and II, with test object positioned between PMMA slices 30
      cm from the II). Exposure parameters varied according to automatic brightness
      control settings. Setup B included X-ray radiation scattered by the patient-PMMA.
      A clinical DQE, describing the transmission of the input signal-to-noise ratio
      associated with both primary and secondary X-ray spectra, was defined.

PMID- 16461534
TI  - Subjective and objective measures of image quality in digital fluoroscopy.
AB  - There are numerous methods for assessing image quality in diagnostic X ray. In
      our study we assessed how imaging quality assurance methods perform in practice.
      Physics assessments were based on IPEM protocols using Leeds test objects.
      Clinical assessment was based on a questionnaire. A total of 15 systems in three
      European locations were assessed, covering a range of image intensifier-TV
      digital fluoroscopy units. Analysis of 274 clinical questionnaires showed that
      clinical and physics assessments did not place systems in the same order, based
      on a given image quality parameter. In almost all the comparisons, low level
      correlation was measured for statistical comparison of rank order (rs < 0.3).
      However, broad agreement was observed between physics and clinical assessments
      for image quality associated with contrast and noise. This study emphasises the
      importance of maintaining links with clinical assessment, when developing quality
      assurance metrics, and measuring the mutual performance of clinical and physical
      assessments of image quality.

PMID- 16461535
TI  - Image quality measurements in radiology.
AB  - Image quality measurement methods are reviewed and difficulties in various
      approaches are highlighted. The main emphasis of the paper is on objective image
      quality measurements, however, subjective assessment methods are also discussed
      briefly.

PMID- 16461536
TI  - Personnel and patient doses: are there ethical consequences to the use of X-rays?
AB  - Interventional cardiology has witnessed a period of great technological change.
      The introduction of new dedicated cardiology X-ray equipment, as well as advances
      in catheter and stent design, has revolutionised clinical practice in cardiology.
      As a consequence, the number, range and complexity of procedures have increased.
      This has meant that patients can be treated as outpatients without requiring
      hospitalisation for surgery. The public are aware of these benefits and demand
      greater access. However, these changes have had an impact on patient and staff
      doses and these are reviewed. Simple approaches to dose reduction for patients
      and staff are illustrated. There are a number of ethical issues concerning both
      patients and staff. For patients, these are related to informed consent. For
      staff, the ethical issues are associated with dose control. These issues will be
      discussed.

PMID- 16461537
TI  - Correlation of patient and staff doses in interventional cardiology.
AB  - The purpose of this study was to measure staff radiation doses in representative
      institutions of five European countries performing coronary angiographies (CA)
      and percutaneous transluminal coronary angioplasties (PTCA), as well as to
      investigate any correlation with patient doses. Patient doses were recorded in
      terms of dose-area product (DAP). Staff doses were measured by thermoluminescence
      dosemeters placed on the operator's left shoulder and left foot. Radiation
      protection measures were also recorded. Third quartile shoulder and foot doses
      were 90 and 66 microSv in CA, and 157 and 173 microSv in PTCA, respectively.
      Shoulder dose was poorly correlated with DAP in CA (R2 = 0.29) and only
      moderately correlated in PTCA (R2 = 0.69). DAP and foot dose correlation was poor
      both in CA (R2 = 0.16) and in PTCA (R2 = 0.02). Protective measures taken by
      staff varied between countries, which may explain the poor correlation of patient
      and staff radiation doses.

PMID- 16461538
TI  - A study to validate the method based on DIMOND quality criteria for cardiac
      angiographic images.
AB  - A method based on image quality criteria (QC) for cine-angiography was developed
      to measure the quality of cine-angiograms (CA). A series of 30 CA for left
      ventriculography (LV) and left and right coronary angiography (LCA, RCA) have
      been scored and 172 readings were obtained. Standard deviation of quality scores
      indicated the reproducibility of the method. Each part of CA was examined
      separately, giving scores for LV, LCA and RCA and a total score (TS), with
      clinical (C) and technical (T) criteria defined and examined separately. In 83%
      of the studies TS was >0.8 and with standard deviation from 0.02 to 0.21. In
      general, LV had a lower score and greater disagreement compared with RCA and LCA.
      Disagreement was greater in T, compared with C. In conclusion, these results
      indicate that QC, translated into a scoring system, yields reproducible data on
      the quality of cardiac images.

PMID- 16461539
TI  - Regulatory aspects of radiation protection.
AB  - The paper introduces the projects launched by the European Community to foster
      prospects in dosimetry, radiation protection and best use of equipment in the
      medical field. These projects are put in perspective with the European legal
      framework for radiation protection, in particular, the Basic Safety Standards
      Directive, the Medical Exposures Directive and the Directive on High-Activity
      Sealed Sources. A summary is given of the overall mission statements of the
      commission services in the field of radiation protection, including the field of
      research, and how they relate to other actions in the overall health policy of
      the EU. In conclusion, a number of priority areas for future work in the medical
      field are highlighted.

PMID- 16461540
TI  - ICRP special radiation protection issues in interventional radiology, digital and
      cardiac imaging.
AB  - The International Commission on Radiological Protection (ICRP) has published two
      reports giving recommendations dealing with the avoidance of deterministic
      injuries in interventional radiology and the management of patient dose in
      digital radiology in 2001 and 2004, respectively. Another document, on radiation
      protection for cardiologists performing fluoroscopically guided procedures, will
      be produced during 2005. This paper highlights some of the topics of the
      published reports, their relevance to European legislation on medical exposures
      and the importance of radiation protection research in underpinning the ICRP task
      groups' work in to producing these documents. It is also anticipated that the
      results, obtained in the cardiology work package of the European research
      project, will be used in the new document on radiation protection for
      cardiologists.

PMID- 16461541
TI  - The ICRU (International Commission on Radiation Units and Measurements): its
      contribution to dosimetry in diagnostic and interventional radiology.
AB  - The ICRU (International Commission on Radiation Units and Measurements was
      created to develop a coherent system of quantities and units, universally
      accepted in all fields where ionizing radiation is used. Although the accuracy of
      dose or kerma may be low for most radiological applications, the quantity which
      is measured must be clearly specified. Radiological dosimetry instruments are
      generally calibrated free-in-air in terms of air kerma. However, to estimate the
      probability of harm at low dose, the mean absorbed dose for organs is used. In
      contrast, at high doses, the likelihood of harm is related to the absorbed dose
      at the site receiving the highest dose. Therefore, to assess the risk of
      deterministic and stochastic effects, a detailed knowledge of absorbed dose
      distribution, organ doses, patient age and gender is required. For interventional
      radiology, where the avoidance of deterministic effects becomes important, dose
      conversion coefficients are generally not yet developed.

PMID- 16461542
TI  - Phosphoinositide-derived messengers in endocrine signaling.
AB  - One of the fundamental questions in endocrinology is how circulating or locally
      produced hormones affect target cell functions by activating specific receptors
      linked to numerous signal-transduction pathways. An important subset of G protein
      coupled cell-surface receptors can activate phospholipase C enzymes to hydrolyze
      a small but critically important class of phospholipids, the phosphoinositides.
      Although this signaling pathway has been extensively explored over the last 20
      years, this has proven to be only the tip of the iceberg, and the multiplicity
      and diversity of the cellular functions controlled by phosphoinositides have
      surpassed any imagination. Phosphoinositides have been found to be key regulators
      of ion channels and transporters, and controllers of vesicular trafficking and
      the transport of lipids between intracellular membranes. Essentially, they
      organize the recruitment and regulation of signaling protein complexes in
      specific membrane compartments. While many of these processes have been
      classically studied by cell biologists, molecular endocrinology cannot ignore
      these recent advances, and now needs to integrate the cell biologist's views in
      the modern concept of how hormones affect cell functions and how derailment of
      simple molecular events can lead to complex endocrine and metabolic disorders.

PMID- 16461543
TI  - Changes in alpha-estradiol receptor and progesterone receptor expression in the
      locus coeruleus and preoptic area throughout the rat estrous cycle.
AB  - We have previously shown that the locus coeruleus (LC) is essential for
      triggering surges of LH. Since LC neurons are responsive to estradiol, which
      induces progesterone receptor (PR) expression, this study aimed to investigate
      whether LC neurons express the alpha-estradiol receptor (alphaER) and PR as well
      as comparing such responses to that observed in the preoptic area (POA). Female
      rats were perfused at 10, 14 and 16 h on each day of the estrous cycle, and a
      blood sample was collected for estradiol, progesterone and LH measurements.
      alphaER- and PR immunoreactive (ir) neurons were detected in POA and LC by
      immunocytochemistry (ICC). Higher plasma estradiol levels were observed on the
      day of proestrus, when a smaller number of alphaER-ir POA neurons were detected.
      An increase in the number of alphaER-ir neurons were observed at 16 h of
      proestrus and estrus. The number of PR-ir neurons increased in POA only at 16 h
      of proestrus, and remained unchanged during all other days and times. The profile
      of alphaER-ir and PR-ir neurons in LC changed over the estrous cycle, with a
      lower expression on metestrus morning and reaching a peak on diestrus afternoon
      before declining on the day of proestrus. However, on estrus afternoon, alphaER
      ir neurons increased, while PR-ir neurons decreased which may be related to the
      prolactin surge of estrus. These data show that LC neurons express alphaER and PR
      and seem to be more sensitive to variations in estradiol than POA. Also, the
      fluctuation in alphaER and PR observed for LC neurons seems to accompany the
      hormonal events that occur during the estrous cycle. This profile of alphaER and
      PR expression might be related to the ability of estradiol and progesterone in
      regulating the activity of LC neurons, which could be associated to the control
      mechanisms of LH and prolactin release.

PMID- 16461544
TI  - Gonadotropin-secreting cells in ovariectomized rats treated with different
      oestrogen receptor ligands: a modulatory role for ERbeta in the gonadotrope?
AB  - In the rat, oestrogen is a key regulator of gonadotrophin synthesis and release
      through activation of oestrogen receptors (ERs). Gonadotropes express alpha and
      beta isoforms of ER and both can activate transcription in response to oestrogen.
      These experiments were aimed at evaluating the relative contribution of ERalpha
      and ERbeta on gonadotrope morphology, progesterone receptor (PR) expression and
      LH secretion. Ovariectomized rats were daily injected over 3 days with 25 microg
      oestradiol benzoate, 0.3 or 1.5 mg of the selective ERalpha agonist
      propylpyrazole triol (PPT) with or without 1.5, 3.0 or 4.5 mg of the selective
      ERbeta agonist diarylpropionitrile (DPN), DPN alone, and 0.3 or 3 mg of
      tamoxifen. Controls were given 0.2 ml oil. Serum concentration and pituitary
      content of LH, gonadotrope PR expression, pituitary PR content, and gonadotrope
      morphology were analyzed by RIA, immunohistochemistry, Western blotting and light
      and electron microscopy, respectively. Results showed that PPT reversed all
      consequences of ovariectomy, DPN mimicked the effects of PPT except for its LH
      releasing action and tamoxifen had ERalpha-like responses. When combined with
      PPT, DPN attenuated ERalpha effects without interfering with its LH-releasing
      activity. Oestradiol benzoate had similar effects to those of combined PPT and
      DPN. It is suggested that (i) the structural reorganization of the cytoplasmic
      organelles provided by oestrogen, and the shrinkage of the ovariectomy-induced
      hypertrophy of gonadotropes, which precedes the expression of PR, are evoked by
      ERalpha and modulated, in a ying-yang fashion, by ERbeta; and (ii) the oestrogen
      dependent exocytosis of LH, the final step in the secretory process, is dependent
      on ERalpha exclusively.

PMID- 16461545
TI  - Estrous cycle dependent changes in expression and distribution of Fas, Fas
      ligand, Bcl-2, Bax, and pro- and active caspase-3 in the rat ovary.
AB  - In the present investigation, the localization of proteins involved in ovarian
      apoptosis were studied throughout the estrous cycle in the presence of
      fluctuating hormone levels. Fas, Fas ligand, Bcl-2, Bax and caspase-3 mRNA
      expression and proteins were detected in all ovarian tissue extracts, though the
      amount of protein varied with the phase of the estrous cycle. Fas, Bax and
      caspase-3 protein levels were highest at diestrus and decreased thereafter
      towards metestrus. In contrast, Fas ligand and Bcl-2 protein levels were lowest
      at diestrus and increased toward metestrus. Immunohistochemistry revealed that
      the staining of the anti-apoptotic protein Bcl-2 was more pronounced in healthy
      preantral follicles than in atretic follicles. In contrast, the pro-apoptotic
      proteins Fas, Fas ligand, Bax and active caspase-3 were more predominantly
      present in atretic follicles. In the ovarian surface epithelium (OSE), Fas,
      procaspase-3 and Bcl-2 immunostaining appeared independent of the phase of the
      estrous cycle. Fas ligand and Bax staining was detected particularly during
      proestrus in OSE cells surrounding the ovulatory follicles, while active caspase
      3 was observed only in OSE cells at the postovulatory site during estrus. The
      proportion of luteal cells that stained positively for Fas, Bax and caspase-3
      increased with the age of the corpus luteum, while Fas ligand and Bcl-2
      immunostaining was strongest in newly formed corpora lutea and decreased
      thereafter. In conclusion, the components of the Fas signalling pathway were
      differentially expressed throughout the estrous cycle in a variety of ovarian
      cell types, which may correspond to hormone dependent survival mechanisms.

PMID- 16461546
TI  - Locally produced estrogen promotes fetal rat metatarsal bone growth; an effect
      mediated through increased chondrocyte proliferation and decreased apoptosis.
AB  - The importance of estrogens for the regulation of longitudinal bone growth is
      unequivocal. However, any local effect of estrogens in growth plate cartilage has
      been debated. Recently, several enzymes essential for estrogen synthesis were
      shown to be expressed in rat growth plate chondrocytes. Local production of
      17beta-estradiol (E2) has also been demonstrated in rat costal chondrocytes. We
      aimed to determine the functional role of locally produced estrogen in growth
      plate cartilage. The human chondrocyte-like cell line HCS-2/8 was used to study
      estrogen effects on cell proliferation (3H-labeled thymidine uptake) and
      apoptosis (cell death detection ELISA kit). Chondrocyte production of E2 was
      measured by RIA and organ cultures of fetal rat metatarsal bones were used to
      study the effects of estrogen on longitudinal growth rate. We found that
      significant amounts of E2 were produced by HCS-2/8 chondrocytes (64.1 +/- 5.3
      fmol/3 days/10(6) cells). The aromatase inhibitor letrozole (1 microM) and the
      pure estrogen receptor antagonist ICI 182,780 (10 microM) inhibited proliferation
      of HCS-2/8 chondrocytes by 20% (P < 0.01) and almost 50% (P < 0.001),
      respectively. Treatment with ICI 182,780 (10 microM) increased apoptosis by 228%
      (P < 0.05). Co-treatment with either caspase-3 or pan-caspase inhibitors
      completely blocked ICI 182,780-induced apoptosis (P < 0.001 vs ICI 182,780 only).
      Moreover, both ICI 182,780 (10 microM) and letrozole (1 microM) decreased
      longitudinal growth of fetal rat metatarsal bones after 7 days of culture (P <
      0.01). In conclusion, our data clearly show that chondrocytes endogenously
      produce E2 and that locally produced estrogen stimulates chondrocyte
      proliferation and protects from spontaneous apoptosis. In addition, longitudinal
      growth is promoted by estrogens locally produced within the epiphyseal growth
      plate.

PMID- 16461547
TI  - Region-specific expression of nitric oxide synthases in the bovine oviduct during
      the oestrous cycle and in vitro.
AB  - Nitric oxide synthases (NOS) account for the endogenous production of nitric
      oxide (NO), a small and permeable bioreactive molecule. NO is known to act as a
      paracrine mediator during various processes associated with female reproduction.
      In the present study, the mRNA expression of the endothelial (eNOS) and inducible
      (iNOS) NO synthases were examined in bovine oviduct epithelial cells (BOEC)
      during the oestrous cycle. In addition, eNOS and iNOS mRNA and protein were
      localised by in situ hybridisation and immunocytochemistry respectively.
      Furthermore, the effects of exogenously applied oestradiol-17beta and
      progesterone on NOS mRNA regulation were studied in a suspension culture of BOEC.
      The eNOS mRNA abundance was low around ovulation (day 0) and increased
      significantly until pro-oestrus (day 18) in the ampulla. Immunoreactive protein
      of eNOS was detected predominantly in endothelial cells as well as in secretory
      oviduct epithelial cells at pro-oestrus. The iNOS mRNA concentration was
      significantly reduced in the isthmus at pro-oestrus (day 18) and oestrus (day 0)
      compared with persistently high levels in the ampulla. By in situ hybridisation,
      specific iNOS transcripts were additionally demonstrated in the oviduct
      epithelium. Immunoreactive iNOS protein was localised in secretory epithelial
      cells as well as in the lamina muscularis. The in vitro stimulation showed that
      both NOS were stimulated by progesterone, but not by oestradiol-17beta. The
      region-specific modulated expression of eNOS and iNOS provides evidence for an
      involvement of endogenously produced NO in the regulation of oviductal functions.

PMID- 16461548
TI  - Bovine follicle development is associated with divergent changes in activin-A,
      inhibin-A and follistatin and the relative abundance of different follistatin
      isoforms in follicular fluid.
AB  - The aim was to determine whether follicle growth in cattle is accompanied by
      changes in levels of inhibin-A (inh-A), activin-A (act-A) and different Mr
      isoforms of follistatin (FS) in bovine follicular fluid (bFF), reflecting
      differential roles of these proteins during folliculogenesis. Follicles (n = 146)
      from 2-20 mm diameter were dissected from ovaries of approximately 40 cattle.
      Immunoassays were used to measure total FS, act-A, inh-A, oestradiol (E) and
      progesterone (P) levels; immunoblotting was used to quantify the relative
      abundance of different FS isoforms. Follicle growth from 2-6 mm was associated
      with a 6-fold increase in inh-A and 30-fold increase in act-A; FS remained
      uniformly high from 2-10 mm. From 6-2 mm, inh-A remained high while act-A and FS
      fell 3-fold and 2-fold, respectively. Act-A/FS ratio increased 20-fold from 2-6
      mm before falling slightly through to 20 mm. Act-A/inh-A ratio increased 6-fold
      from 2-6 mm before falling 2-fold from 6 to 17-20 mm. These findings imply a
      marked increase in relative activin 'tone' around the stage at which dominant
      follicle selection occurs. When larger follicles (13-20 mm) were subdivided
      according to E/P ratio, those with high ( > 5) E/P ratio had lower (2-fold; P <
      0.001) levels of inh-A and act-A in comparison to follicles with low ( < 5) E/P
      ratio, but there were no significant differences in FS, act-A/inh-A ratio or act
      A/FS ratio. Thus follicle size, but not oestrogenic status, has a major influence
      on the intrafollicular balance between act-A and its opposing factors, inh-A and
      FS. Six FS isoforms were detected in bFF (apparent Mr: 65, 41, 37, 35, 33 and 31
      kDa) averaging 6, 13, 24, 26, 13 and 17% respectively of total FS. During growth
      from 2-20 mm the proportion of total FS represented by 65, 41 and 37 kDa isoforms
      increased approximately 2-fold while the proportion represented by the 33 and 31
      kDa isoforms decreased by 3-fold and 1.6-fold, respectively. Treatment of bovine
      granulosa cells in vitro with FSH and IGF alone or in combination increased total
      FS secretion up to 12-fold but did not affect the relative abundance of the five
      different FS isoforms detected. While the functional significance of the
      intriguing shift in FS isoform abundance in bFF during follicle development
      remains to be established, we have shown that a marked increase in
      intrafollicular activin 'tone' accompanies bovine follicle growth from 3-6 mm,
      corresponding to the stage at which the FSH-dependent follicle selection
      mechanism operates in this species.

PMID- 16461549
TI  - Luteinizing hormone inhibits Fas-induced apoptosis in ovarian surface epithelial
      cell lines.
AB  - Gonadotrophins including LH have been suggested to play an important role in the
      etiology of epithelial ovarian cancers. The goal of the present study was to
      obtain more insight in the mechanism of gonadotrophin action on ovarian surface
      epithelium (OSE) cells. As the Fas system is known to be a major player in the
      regulation of the process of apoptosis in the ovary, we investigated whether LH
      interfered with Fas-induced apoptosis in the human OSE cancer cell lines HEY and
      Caov-3. Activation of Fas receptor by an agonistic anti-Fas receptor antibody
      induced apoptosis, as was evaluated by caspase-3 activation, poly(ADP-ribose)
      polymerase fragmentation, phosphatidylserine externalization and morphological
      changes characteristic of apoptosis. Co-treatment with LH reduced the number of
      apoptotic cells following activation of Fas in a transient manner, while LH by
      itself did not affect apoptosis or cell proliferation. The anti-apoptotic effect
      of LH could be mimicked by the membrane-permeable cAMP analog 8-(4
      chlorophenylthio) cAMP (8-CPT-cAMP), and blocked by H89, a specific inhibitor of
      protein kinase A (PKA). In conclusion, these findings suggest that LH protects
      HEY cells against Fas-induced apoptosis through a signaling cascade involving
      PKA. Although it is plausible that in vivo LH might also enhance OSE tumor growth
      through inhibition of apoptosis, further research is necessary to confirm this
      hypothesis.

PMID- 16461550
TI  - Differential expression of mRNAs encoding the putative inhibin co-receptor
      (betaglycan) and activin type-I and type-II receptors in preovulatory and
      prehierarchical follicles of the laying hen ovary.
AB  - Ovarian follicle development is primarily regulated by an interplay between the
      pituitary gonadotrophins, LH and FSH, and ovary-derived steroids. Increasing
      evidence implicates regulatory roles of transforming growth factor-beta (TGFbeta)
      superfamily members, including inhibins and activins. The aim of this study was
      to identify the expression of mRNAs encoding key receptors of the inhibin/activin
      system in ovarian follicles ranging from 4 mm in diameter to the dominant F1
      follicle (approximately 40 mm). Ovaries were collected (n = 16) from mid-sequence
      hens maintained on a long-day photoschedule (16 h of light:8 h of darkness). All
      follicles removed were dissected into individual granulosa and thecal layers. RNA
      was extracted and cDNA synthesized. Real-time quantitative PCR was used to
      quantify the expression of mRNA encoding betaglycan, activin receptor (ActR)
      subtypes (type-I, -IIA and -IIB) and glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH); receptor expression data were normalized to GAPDH expression. Detectable
      levels of ActRI, -IIA and -IIB and the inhibin co-receptor (betaglycan)
      expression were found in all granulosa and thecal layers analysed. Granulosa
      ActRI mRNA peaked (P < 0.05) in 8-9.9 mm follicles, whereas ActRIIA rose
      significantly from 6-7.9 mm to 8-9.9 mm, before falling to F3/2; levels then rose
      sharply (3-fold) to F1 levels. Granulosa betaglycan mRNA expression rose 3-fold
      from 4-5.9 mm to 8-9.9 mm, before falling 4-fold to F3/2; levels then rose
      sharply (4-fold) to F1 levels. ActRIIB levels did not vary significantly during
      follicular development. Thecal ActRI mRNA expression was similar from 4-7.9 mm
      then decreased significantly to a nadir at the F4 position, before increasing 2
      fold to the F1 (P < 0.05). Although thecal ActRIIB and -IIA expression did not
      vary significantly from 4 mm to F3, ActRIIB expression increased significantly (2
      fold) from F3 to F1 and ActRIIA increased 2-fold from F2 to F1 (P < 0.05). Thecal
      betaglycan fell to a nadir at F6 after follicle selection; levels then increased
      significantly to F2, before falling approximately 50% in the F1. In all follicles
      studied expression of betaglycan and ActRI (granulosa: r = 0.65, P < 0.001, n =
      144/group; theca: r = 0.49, P < 0.001, n = 144/group) was well correlated. No
      significant correlations were identified between betaglycan and ActRIIA or -IIB.
      Considering all follicles analysed, granulosa mRNA expression of betaglycan,
      ActRI, ActRIIA and ActRIIB were all significantly lower than in corresponding
      thecal tissue (betaglycan, 11.4-fold; ActRIIB, 5.1-fold; ActRI, 3.8-fold;
      ActRIIA, 2.8-fold). The co-localization of type-I and -II activin receptors and
      betaglycan on granulosa and thecal cells are consistent with a local
      auto/paracrine role of inhibins and activins in modulating ovarian follicle
      development, selection and progression in the domestic fowl.

PMID- 16461551
TI  - A 36 residues insertion in the dimerization domain of the growth hormone receptor
      results in defective trafficking rather than impaired signaling.
AB  - Growth hormone insensitivity syndrome (GHIS) has been reported in a family
      homozygous for a point mutation in the GH receptor (GHR) that activates an
      intronic pseudoexon. The resultant GHR (GHR1-656) includes a 36 amino-acids
      insertion after residue 207, in the region known to be important for
      homodimerization of GHR. We have examined the functional consequences of such an
      insertion in mammalian cells transfected with the wild type (GHRwt) and mutated
      GHR (GHR1-656). Radio-ligand binding and flow cytometry analysis showed that GHR1
      656 is poorly expressed at the cell surface compared with GHRwt. Total membrane
      binding and Western blot analysis showed no such difference in the level of total
      cellular GHR expressed for GHR1-656 vs GHRwt. Immunofluorescence showed GHR1-656
      to have different cellular distribution to the wild type receptor (GHRwt), with
      the mutated GHR being mainly perinuclear and less vesicular than GHRwt. Western
      blot analysis showed GH-induced phosphorylation of Jak2 and Stat5 for both GHR1
      656 and GHRwt, although reduced Stat5 activity was detected with GHR1-656,
      consistent with lower levels of expression of GHR1-656 than GHRwt at the cell
      surface. In conclusion, we report that GHIS, due to a 36 amino-acids insertion in
      the extracellular domain of GHR, is likely to be explained by a trafficking
      defect rather than by a signalling defect of GHR.

PMID- 16461552
TI  - Differential responses of the growth hormone axis in two rat models of
      streptozotocin-induced insulinopenic diabetes.
AB  - The impact of streptozotocin (STZ)-induced, insulinopenic diabetes on the GH axis
      of rats and mice differs from study to study, where this variation may be related
      to the induction scheme, severity of the diabetes and/or the genetic background
      of the animal model used. In order to begin differentiate between these
      possibilities, we compared the effects of two different STZ induction schemes on
      the GH axis of male Sprague-Dawley rats: (1) a single high-dose injection of STZ
      (HI STZ, 80 mg/kg, i.p.), which results in rapid chemical destruction of the
      pancreatic beta-cells, and (2) multiple low-dose injections of STZ (LO STZ, 20
      mg/kg for 5 consecutive days, i.p.), which results in a gradual, autoimmune
      destruction of beta-cells. STZ-treated animals were killed after 3 weeks of
      hyperglycemia (>400 mg/dl), and in both paradigms circulating insulin levels were
      reduced to <40% of vehicle-treated controls. HI STZ-treated rats lost weight,
      while body weights of LO STZ-treated animals gradually increased over time,
      similar to vehicle-treated controls. As previously reported, HI STZ resulted in a
      decrease in circulating GH and IGF-I levels which was associated with a rise in
      hypothalamic neuropeptide Y (NPY) mRNA (355% of vehicle-treated controls) and a
      fall in GH-releasing hormone (GHRH) mRNA (45% of vehicle-treated controls)
      levels. Changes in hypothalamic neuropeptide expression were reflected by an
      increase in immunoreactive NPY within the arcuate and paraventricular nuclei and
      a decrease in GHRH immunoreactivity in the arcuate nucleus, as assessed by
      immunohistochemistry. Consistent with the decline in circulating GH and
      hypothalamic GHRH, pituitary GH mRNA levels of HI STZ-treated rats were 58% of
      controls. However, pituitary receptor mRNA levels for GHRH and ghrelin increased
      and those for somatostatin (sst2, sst3 and sst5) decreased following HI STZ
      treatment. The impact of LO STZ treatment on the GH axis differed from that
      observed following HI STZ treatment, despite comparable changes in circulating
      glucose and insulin. Specifically, LO STZ treatment did suppress circulating IGF
      I levels to the same extent as HI STZ treatment; however, the impact on
      hypothalamic NPY mRNA levels was less dramatic (158% of vehicle-treated controls)
      where NPY immunoreactivity was increased only within the paraventricular nucleus.
      Also, there were no changes in circulating GH, hypothalamic GHRH or pituitary
      receptor expression following LO STZ treatment, with the exception that pituitary
      sst3 mRNA levels were suppressed compared with vehicle-treated controls. Taken
      together these results clearly demonstrate that insulinopenia, hyperglycemia and
      reduced circulating IGF-I levels are not the primary mediators of hypothalamic
      and pituitary changes in the GH axis of rats following HI STZ treatment. Changes
      in the GH axis of HI STZ-treated rats were accompanied by weight loss, and these
      changes are strikingly similar to those observed in the fasted rat, which
      suggests that factors associated with the catabolic state are critical in
      modifying the GH axis following STZ-induced diabetes.

PMID- 16461553
TI  - The G972R variant of the insulin receptor substrate-1 gene impairs insulin
      signaling and cell differentiation in 3T3L1 adipocytes; treatment with a
      PPARgamma agonist restores normal cell signaling and differentiation.
AB  - The insulin receptor substrate-1 (IRS-1) plays a central role in insulin
      sensitivity, and association studies have shown that the IRS-1 G972R variant is a
      risk factor for insulin resistance. However, how this mutation may lead to
      impaired insulin sensitivity is still to be determined. Our study aimed to
      evaluate, after transfection of the IRS-1 G972R variant in 3T3L1 adipocytes, the
      effect of this mutation on insulin signaling and on cell differentiation. The
      3T3L1 cells were transfected with pcDNA3 expression vector containing either the
      human wild-type IRS-1 or the G972R variant. After induction of differentiation,
      the 3T3L1 transfected with wild-type IRS-1 differentiated in 6-8 days, while the
      cells transfected with G972R variant did not differentiate. To determine whether
      the defect in IRS-1 was responsible for this, we analyzed the expression of
      several genes involved in the insulin signaling pathway. Results showed that
      PPARgamma expression was significantly reduced in cells transfected with the
      mutated IRS-1, together with a significant decrease in binding of
      phosphatidylinositol-3 kinase (PI 3-kinase) to IRS-1 G972R and in PI 3-kinase
      activity. In addition, we observed that the interaction between the insulin
      receptor (IR) and the IRS-1 G972R protein was increased and that the
      autophosphorylation of the IR was significantly inhibited in 3T3L1-G972R cells
      compared with 3T3L1-WT. Treatment of the 3T3L1-G972R cells with pioglitazone
      (PIO), a PPARgamma agonist, restored differentiation with higher level of
      PPARgamma expression and restoration of PI 3-kinase binding to IRS-1 G972R and PI
      3-kinase activity. IR autophosphorylation was also increased. Withdrawal of PIO
      in fully differentiated 3T3L1-G972R cells determined the reappearance of the
      insulin signaling defect. Finally, we observed higher levels of IRS-2 expression,
      suggesting that IRS-2 may play a more important role in adipocyte insulin
      signaling. In conclusion, IRS-1 G972R variant impairs insulin signaling, and
      treatment with PPARgamma agonist restores the normal phenotype of 3T3L1 cells.

PMID- 16461554
TI  - Involvement of PDX-1 in activation of human insulin gene transcription.
AB  - Islet beta cell-specific transcription of the insulin gene is mediated through
      the binding of the islet-enriched PDX-1, BETA2, and MafA transcription factors to
      conserved 5'-flanking region regulatory elements. However, additional non
      conserved sequences within this region are also significant in regulating
      expression. Thus, PDX-1 binds to and activates the GG2 element located between
      nucleotides -145 and -140 of the human gene, while the corresponding, but non
      identical, site in the rodent insulin genes are negatively regulated by the
      Nkx2.2 transcription factor. Here, we show that despite binding PDX-1
      approximately 20-fold less effectively than the conserved insulin A3 and A1 sites
      in gel mobility shift assays, human GG2 appears to be more important for the
      activation of transfected human insulin enhancer-driven reporter constructs in
      beta cell lines. Furthermore, functional interaction analysis in non-islet cell
      lines demonstrated that PDX-1 binding to GG2, A1, and A3 contributes to
      synergistic activation of insulin gene expression with MafA. Our analysis also
      illustrated the requirement of poorly conserved human sequences between -293 and 
      251 in mediating activity through the more upstream A3 binding site. Collectively
      these experiments have revealed distinct features in control of the human and
      rodent insulin genes by PDX-1, processes that may be involved in regulating
      insulin expression under both normal and diabetic conditions in humans.

PMID- 16461555
TI  - Diabetes causes marked changes in function and metabolism of rat neutrophils.
AB  - Several studies have shown impairment of neutrophil function, a disorder that
      contributes to the high incidence of infections in diabetes. Since glucose and
      glutamine play a key role in neutrophil function, we investigated their
      metabolism in neutrophils obtained from the peritoneal cavity of streptozotocin
      induced diabetic rats. The activities of hexokinase, glucose-6-phosphate
      dehydrogenase (G6PDH), phosphofructokinase (PFK), citrate synthase, phosphate
      dependent glutaminase, NAD+-linked and NADP+-linked isocitrate dehydrogenase were
      assayed. Glucose, glutamine, lactate, glutamate and aspartate, and the
      decarboxylation of [U-14C], [1-14C] and [6-14C]glucose; [U-14C]palmitic acid; and
      [U-14C]glutamine were measured in 1-h incubated neutrophils. Phagocytosis
      capacity and hydrogen peroxide (H2O2) production were also determined. All
      measurements were carried out in neutrophils from control, diabetic and insulin
      treated (2-4 IU/day) diabetic rats. Phagocytosis and phorbol myristate acetate
      (PMA)-stimulated H2O2 production were decreased in neutrophils from diabetic
      rats. The activities of G6PDH and glutaminase were decreased, whereas that of PFK
      was raised by the diabetic state. The activities of the remaining enzymes were
      not changed. Diabetes decreased the decarboxylation of [1-14C]glucose and [U
      14C]glutamine; however, [6-14C]glucose and [U-14C]palmitic acid decarboxylation
      was increased. These observations indicate that changes in metabolism may play an
      important role in the impaired neutrophil function observed in diabetes. The
      treatment with insulin abolished the changes induced by the diabetic state even
      with no marked change in glycemia. Therefore, insulin may have a direct effect on
      neutrophil metabolism and function.

PMID- 16461556
TI  - Inhibition of DNA methylation increases follistatin expression and secretion in
      the human adrenocortical cell line NCI-H295R.
AB  - Activin affects adrenocortical steroidogenesis and increases apoptosis, while
      follistatin (FS) acts as an activin antagonist by binding to activin, preventing
      attachment to its receptors. The regulation of FS expression in the adrenal
      cortex is poorly understood. Adrenocortical tumors often display aberrant
      methylation. In the present study, we investigated the effect of DNA methylation
      on FS mRNA expression and peptide secretion in adrenocortical cells. We treated
      human NCI-H295R adrenocortical cells with the methylation inhibitor 5-Aza
      2'deoxycytidine (Azad; 0.1-100 microM for 1, 4 or 7 days) and measured FS mRNA
      expression by Northern blot and quantitative real time RT-PCR analyses as well as
      FS secretion by specific ELISA. Methylation-specific PCR showed decreased
      methylation in the FS promoter region after Azad treatment. A significant (P <
      0.05) time- and dose-dependent increase in FS mRNA expression (up to 4.6-fold)
      and peptide secretion (up to 17.1-fold) was detected after Azad treatment. We
      conclude that FS gene expression and peptide secretion in NCI-H295R
      adrenocortical cells are regulated by DNA methylation. Thus, variable methylation
      in different adrenocortical tumors may influence activin bioactivity and its
      consequences in steroidogenesis and cell proliferation/apoptosis.

PMID- 16461557
TI  - Glucocorticoids enhance cytotoxicity of cisplatin via suppression of NF-{kappa}B
      activation in the glucocorticoid receptor-rich human cervical carcinoma cell line
      SiHa.
AB  - Glucocorticoids (GCs) are commonly co-administered with cisplatin in the
      treatment of patients with carcinomas to prevent drug-induced allergic reaction,
      nausea and vomiting. Although GC receptor (GR) is ubiquitous in carcinoma cells
      and has been linked to signal transduction pathways pertinent to cell growth and
      apoptosis, little is known regarding the possible effect of GC on the
      chemosensitivity of carcinomas. Our previous study demonstrated that
      dexamethasone (DEX) enhances the cytotoxicity to cisplatin in a GR-rich human
      cervical carcinoma cell line, SiHa. In this study, we found that this cisplatin
      cytotoxicity-enhancing effect of DEX correlated well with its effect on
      abrogating the cisplatin-induced activation of nuclear factor kappa B (NF
      kappaB). RU486, a structural homologue of DEX, partially reversed this
      cytotoxicity-enhancing effect of DEX, a finding consistent with the well-known
      partial reversing effect of RU486 on DEX-induced NF-kappaB suppression.
      Furthermore, expression of a dominant-negative truncated IkappaBalpha gene in
      SiHa cells completely abolished the cisplatin cytotoxicity-enhancing effect of
      DEX. Our data suggest that the specific action of DEX on GR may enhance the
      cytotoxicity of cisplatin in selected GR-rich cancer cells by suppressing NF
      kappaB activation.

PMID- 16461558
TI  - Suppressive effects of dehydroepiandrosterone and the nuclear factor-kappaB
      inhibitor parthenolide on corticotroph tumor cell growth and function in vitro
      and in vivo.
AB  - Dehydroepiandrosterone (DHEA) is believed to have an anti-tumor effect, as well
      as anti-inflammatory, antioxidant, and anti-aging effects. To clarify the
      possible inhibitory action of DHEA on pituitary tumor cells, we tested the
      effects of DHEA, alone or in combination with the nuclear factor-kappaB (NF
      kappaB) inhibitor parthenolide (PRT), on AtT20 corticotroph cell growth and
      function both in vitro and in vivo. We found that, in vitro, DHEA and PRT had
      potent inhibitory effects on pro-opiomelanocortin and NF-kappaB-dependent gene
      expression. They also suppressed the transcription activity of survivin, a
      representative anti-apoptotic factor, and induced apoptosis in this cell line.
      Furthermore, using BALB/C nude mice with xenografts of AtT20 cells in vivo, we
      found that the combined administration of DHEA and PRT significantly attenuated
      tumor growth and survivin expression. The treatment also decreased the elevated
      plasma corticosterone levels and ameliorated the malnutrition induced by tumor
      growth. Altogether, these results suggested that combined treatments of DHEA and
      PRT potently inhibit the growth and function of corticotroph tumor cells both in
      vitro and in vivo. This effect may, at least partly, be caused by the suppressive
      effects of these compounds, such as survivin and other inhibitor of apoptosis
      proteins, on NF-kappaB-mediated gene transcription.

PMID- 16461559
TI  - Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated
      ghrelin in elderly females correlate positively with serum IGF-I levels and bowel
      movement frequency and negatively with systolic blood pressure.
AB  - Aging is associated with a decrease in growth hormone (GH) secretion, appetite
      and energy intake. As ghrelin stimulates both GH secretion and appetite,
      reductions in ghrelin levels may be involved in the reductions in GH secretion
      and appetite observed in the elderly. However, only preliminary studies have been
      performed on the role of ghrelin in elderly subjects. In this study, we sought to
      clarify the physiologic implications of the age-related alterations in ghrelin
      secretion by determining plasma ghrelin levels and other clinical parameters in
      healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the
      SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and
      had not been treated with hormones. One hundred and five volunteers (49 men and
      56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of
      acylated ghrelin in elderly female subjects positively correlated with serum IGF
      I levels and bowel movement frequency and negatively with systolic blood
      pressure. In elderly men, desacyl ghrelin levels correlated only weakly with
      bowel movement frequency. These findings suggest that the plasma levels of the
      acylated form of ghrelin may influence the age-related alterations in GH/IGF-I
      regulation, blood pressure and bowel motility. These observational associations
      warrant further experimental studies to clarify the physiologic significance of
      these effects.

PMID- 16461560
TI  - Long isoform of prolactin receptor predominates in rat intrahepatic bile ducts
      and further increases under obstructive cholestasis.
AB  - Prolactin participates in the regulation of liver function. However, prolactin
      receptor (PrlR) expression and its regulation have been described only for
      hepatocytes. In this study, we investigated the expression and regulation of PrlR
      isoforms in the other important intrahepatic cellular compartment: the biliary
      epithelial cells, or cholangiocytes. Our aim was to determine whether prolactin
      should be considered as a potential regulator of cholangiocyte function under
      normal and pathological conditions. Cholangiocytes and hepatocytes were
      differentially isolated from rat liver. PrlR expression was analysed at the mRNA
      level by isoform-specific semiquantitative PCR, and at the protein level by
      immunostaining of liver sections. Hormonal regulation of PrlR expression was
      evaluated by comparing intact rats with gonadectomized, pituitary-grafted or
      bromocriptine-treated animals. Common bile-duct ligation was used as the
      experimental model of cholestasis. Our results demonstrate that the expression
      pattern and regulation of PrlR isoforms is totally different in cholangiocytes
      compared with hepatocytes: (1) mature rat cholangiocytes express low levels of
      PrlR, while it is very high in hepatocytes, (2) only the long isoform is detected
      in cholangiocytes, while the short isoform predominates in hepatocytes and (3)
      PrlR levels in cholangiocytes are induced by obstructive cholestasis, but not by
      sex hormones or prolactin, while it is the opposite in hepatocytes. From these
      data, the actions of prolactin on liver are anticipated to exhibit strong cell
      type specificity in both normal and pathological conditions.

PMID- 16461561
TI  - The pro-opiomelanocortin genes in rainbow trout (Oncorhynchus mykiss):
      duplications, splice variants, and differential expression.
AB  - Pro-opiomelanocortin (POMC) is a precursor for several important peptide hormones
      involved in a variety of functions ranging from stress response to energy
      homeostasis. In mammals and fish, the POMC-derived peptide alpha-melanocyte
      stimulating hormone (MSH) is known to be involved in appetite suppression through
      its interaction with melanocortin-4 receptors. The details of energy homeostasis
      in fishes are beginning to be elucidated and many of the genes involved in
      mammalian neuroendocrine signaling pathways are being discovered in fish. In
      salmonid fishes such as the rainbow trout, genome duplication adds another degree
      of complexity when trying to compare gene function and homology with other
      vertebrates. This is true of the POMC gene. Two copies of the POMC gene were
      previously identified, A and B, presumably resulting from the salmonid
      duplication. However, while investigating POMC involvement in the feeding
      response of rainbow trout, a second copy of POMC-A was discovered which is more
      likely the result of the salmonid duplication and suggests that POMC-B is a
      duplicate resulting from the earlier teleost duplication prior to tetrapod
      divergence. The duplicated POMC-A had five deleted amino acids, five inserted
      amino acids, and 39 amino acid differences from the published POMC-A. In addition
      to the duplicate POMC-A, a splice variant of the published POMC-A sequence was
      also identified. Quantitative real-time PCR assays were developed for the
      different POMC transcripts, and expression was examined in a variety of tissues.
      Expression of POMC transcripts was highest in the pituitary for all POMC genes,
      but varied among other tissues for POMC-A1, POMC-A2, POMC-A2s, and POMC-B. POMC
      A1 was the only transcript to respond significantly to food deprivation.

PMID- 16461562
TI  - Both N-terminal and C-terminal regions of steroid sulfatase are important for
      enzyme activity.
AB  - Steroid sulfatase (STS) is localized in the endoplasmic reticulum and catalyzes
      desulfation of 3beta-hydroxysteroid sulfates. X-linked ichthyosis (XLI) is an
      inherited skin disorder caused by deficiency of STS enzyme activity. We
      previously reported a case in which XLI with a one-base change in the STS gene
      and variation in amino acid Q560P developed. In this study, we performed
      molecular analysis to determine the importance of terminal regions of STS and the
      effect of mutant STS on STS enzyme activity. To examine the effect of terminal
      truncated STS on the enzyme activity, N- and C-terminal truncated STS expression
      vectors were transfected into COS-1 cells. The activity of truncated STS lacking
      the N-terminal regions declined, and the activity of C-terminal-truncated STS
      declined with extension of the truncated C-terminal region. Although the results
      of pulse-chase experiments showed that a one-base mutant STS (Q560P) and C
      terminal-truncated STS (deltaC2 (1-559)) had no effects on protein synthesis and
      degradation, the mutant STS and C-terminal-truncated STS have dominant negative
      effect on STS enzyme activity when the STS mutant or truncated STS protein and a
      wild-type STS protein coexist in cells. Results of coprecipitation of the
      truncated STS with an STS-FLAG fusion protein showed that STS formed a dimer
      conformation in cells. In this study, we have shown that both the N-terminal
      region and C-terminal region are important for STS enzyme activity. The C
      terminal mutant has a dominant negative effect on wild-type STS.

PMID- 16461563
TI  - Phosphohistone H3 labelling for histoprognostic grading of breast adenocarcinomas
      and computer-assisted determination of mitotic index.
AB  - BACKGROUND: Microscopic evaluation of mitotic figures is a routine procedure in
      the assessment of the histoprognostic grade of tumours. Nevertheless, their count
      may be fraught with difficulties. As histone H3 phosphorylation at serine 10 is
      closely linked to chromosomal condensation, a new monoclonal antibody directed to
      phosphorylated histone H3 (PPH3) was recently proposed to detect mitotic cells.
      AIM: To test the reliability of this antibody in detecting and counting mitotic
      figures in sections of breast adenocarcinomas, because of the importance of
      mitotic count in histoprognostic grading. METHODS: The pattern of PPH3 staining
      in formalin-fixed paraffin wax-embedded tissues, including normal tissues and a
      series of 39 breast adenocarcinomas, was examined. A new computer-assisted method
      was also developed for determining the mitotic index. RESULTS AND CONCLUSIONS: In
      all tissues tested, PPH3-labelled mitotic figures were easily detected, allowing
      a rapid identification of the area of highest mitotic activity. In breast
      carcinomas, a strong correlation was observed between PPH3-stained and
      haematoxylin and eosin-stained mitotic counts (r = 0.86, p<0.0001). Counting of
      prophase nuclei that coexpress cyclin B1, a marker of the G2/M phase, was
      possible by PPH3 staining; its accuracy led us to reconsider the tumour grade in
      three cases. Finally, an automatic computer-assisted method was designed for
      assessing mitotic index with confocal microscopy and image-analysis software.

PMID- 16461564
TI  - Computerised pathology test order entry reduces laboratory turnaround times and
      influences tests ordered by hospital clinicians: a controlled before and after
      study.
AB  - OBJECTIVE: To assess the impact of a computerised pathology order entry system on
      laboratory turnaround times and test ordering within a teaching hospital.
      METHODS: A controlled before and after study compared test assays ordered from 11
      wards two months before (n = 97 851) and after (n = 113 762) the implementation
      of a computerised pathology order entry system (Cerner Millennium Powerchart).
      Comparisons were made of laboratory turnaround times, frequency of tests ordered
      and specimens taken, proportions of patients having tests, average number per
      patient, and percentage of gentamicin and vancomycin specimens labelled as
      random. RESULTS: Intervention wards experienced an average decrease in turnaround
      of 15.5 minutes/test assay (range 73.8 to 58.3 minutes; p<0.001). Reductions were
      significant for prioritised and non-prioritised tests, and for those done within
      and outside business hours. There was no significant change in the average number
      of tests (p = 0.228), or specimens per patient (p = 0.324), and no change in
      turnaround time for the control ward (p = 0.218). Use of structured order screens
      enhanced data provided to laboratories. Removing three test assays from the liver
      function order set resulted in significantly fewer of these tests being done.
      CONCLUSIONS: Computerised order entry systems are an important element in
      achieving faster test results. These systems can influence test ordering patterns
      through structured order screens, manipulation of order sets, and analysis of
      real time data to assess the impact of such changes, not possible with paper
      based systems. The extent to which improvements translate into improved patient
      outcomes remains to be determined. A potentially limiting factor is clinicians'
      capacity to respond to, and make use of, faster test results.

PMID- 16461565
TI  - Prognostic significance of E-cadherin-catenin complex in epithelial ovarian
      cancer.
AB  - OBJECTIVE: To clarify the prognostic role of E-cadherin and beta- and gamma
      catenins, and their relation to CD44 in epithelial ovarian carcinoma. METHODS:
      The expression of E-cadherin and beta- and gamma-catenins was analysed
      immunohistochemically in 305 primary epithelial ovarian cancers and 44
      metastases, and related to CD44 expression, clinicopathological factors, and the
      patients' survival. RESULTS: Reduced cell surface expression of E-cadherin, beta
      catenin, and gamma-catenin was particularly frequent in serous and endometrioid
      histological types. Reduced cell surface expression of E-cadherin and beta
      catenin was also associated with poor differentiation. Nuclear positivity of beta
      catenin was associated with high CD44 expression, endometrioid histology, and
      local stage of the tumour, whereas nuclear gamma-catenin expression was
      associated with serous histology and poor differentiation. In the univariate
      analysis, preserved cell surface beta-catenin expression in the whole study
      material and nuclear expression of beta- and gamma-catenins in the subgroup of
      endometrioid ovarian cancers were predictors of better 10 year disease related
      survival. Preserved cell surface expression of E-cadherin and beta-catenin
      predicted favourable recurrence-free survival. These statistical significances
      were not retained in multivariate analysis. CONCLUSIONS: The correlation between
      nuclear beta-catenin and CD44 indicates that beta-catenin may regulate the
      transcription of CD44 in epithelial ovarian cancer. E-cadherin-catenin complex
      members are associated with the prognosis of patients with epithelial ovarian
      cancer, but these univariate associations were not strong enough to compete for
      significance with the traditional clinicopathological factors.

PMID- 16461566
TI  - Specific epitopes of the structural and hypothetical proteins elicit variable
      humoral responses in SARS patients.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is an infectious disease
      which was caused by a novel coronavirus (SARS-CoV). SARS has caused an outbreak
      in the world during 2003 and 2004, with 8098 individuals being infected and a
      death toll of 774 in 28 regions around the world. Specific humoral responses to
      viral infection remain unclear. OBJECTIVE: To analyse the antigenicity of the
      SARS-CoV genome and identify potential antigenic epitopes in the structural
      proteins. METHODS: Potential antigenic epitopes were identified in the structural
      proteins (nucleocapsid, membrane, spike, and small envelope proteins) and
      hypothetical proteins (SARS3a, 3b, 6, 7a, and 9b) that are specific for SARS-CoV.
      A peptide chip platform was created and the profiles of antibodies to these
      epitopes were investigated in 59 different SARS patients' sera obtained 6-103
      days after the onset of the illness. Serial sera from five additional patients
      were also studied. RESULTS: Epitopes at the N-terminus of the membrane protein
      and the C-terminus of nucleocapsid protein elicited strong antibody responses.
      Epitopes on the spike protein were only moderately immunogenic but the effects
      were persistent. Antibodies were also detected for some putative proteins,
      noticeably the C-termini of SARS3a and SARS6. CONCLUSIONS: Important epitopes of
      the SARS-CoV genome that may serve as potential markers for the viral infection
      are identified. These specific antigenic sites may also be important for vaccine
      development against this new fatal infectious disease.

PMID- 16461567
TI  - Serum HER-2 concentration in patients with primary breast cancer.
AB  - OBJECTIVE: To evaluate whether serum HER-2/neu (HER-2) concentration is a valid
      index of HER-2 status in women with primary breast cancer, and to establish a
      normal reference range for serum HER-2 concentration in Korean women. METHODS:
      Serum HER-2 concentration was measured and immunohistochemistry (IHC) and
      fluorescence in situ hybridisation (FISH) carried out on tissue samples from 86
      consecutive female patients. The results of the three datasets were compared. The
      cut off value of HER-2 concentration was determined from the mean +2SD values
      derived from the serum of 93 healthy volunteers. RESULTS: The IHC and FISH data
      were significantly correlated (p<0.01), but neither showed significant
      correlation with the serum HER-2 data. The cut off value of serum HER-2 was 10.2
      microg/l, and the serum HER-2 concentration of patients with primary breast
      cancer ranged from 5.0 to 17.5 microg/l. Only five patients had a serum HER-2
      value above the cut off value. CONCLUSIONS: Serum HER-2 concentration cannot be
      substituted for IHC or FISH to evaluate HER-2 status, nor can it be used as a
      diagnostic tumour marker in primary breast cancer, considering the low prevalence
      of serum HER-2 elevation.

PMID- 16461568
TI  - Enumeration and immunohistochemical characterisation of bone marrow basophils in
      myeloproliferative disorders using the basophil specific monoclonal antibody 2D7.
AB  - BACKGROUND: Basophils are highly specialised granulocytes that express a unique
      profile of antigens and increase in myeloproliferative disorders (MPD). In
      chronic myeloid leukaemia (CML), basophilia is a diagnostic and prognostic
      determinant. So far, however, no reliable approach for routine detection and
      enumeration of bone marrow basophils has become available. OBJECTIVE: To detect
      and enumerate basophils in bone marrow sections in patients with CML and other
      MPD. METHODS: The anti-basophil antibody 2D7 was applied to paraffin embedded
      bone marrow sections from normal/reactive subjects (n = 31), patients with CML
      (chronic phase, n = 37; accelerated phase, n = 9), and other MPD (chronic
      idiopathic myelofibrosis (CIMF), n = 20; polycythaemia vera (PV), n = 20;
      essential thrombocythaemia (ET), n = 20; indolent systemic mastocytosis (ISM), n
      = 7). RESULTS: As assessed by serial section staining, 2D7(+) cells were found to
      co-express myeloperoxidase, histidine decarboxylase, CD9, and CD43, but did not
      express B cell or T cell restricted antigens. 2D7(+) bone marrow cells were found
      to increase in CML compared with normal/reactive bone marrow and other MPD
      (median numbers of 2D7(+) cells/mm(2): CML, 33; normal/reactive bone marrow, 6;
      CIMF, 10; PV, 6; ET, 5; ISM, 3; p<0.05). The highest basophil counts were
      recorded in accelerated phase CML (115/mm(2)). CONCLUSIONS: A novel
      immunohistochemical procedure has been established for basophil detection in
      normal bone marrow and MPD. This approach should help in the quantification of
      bone marrow basophils at diagnosis and during anti-leukaemic treatment.

PMID- 16461569
TI  - Renal medullary changes in renal allograft recipients with raised serum
      creatinine.
AB  - OBJECTIVE: To test the hypothesis that the renal medulla may reflect rejection
      related changes and thus have a predictive value in the assessment of acute renal
      allograft rejection or chronic graft damage. METHODS: 75 post-transplant biopsies
      from 57 patients were scored according to the Banff 1997 scheme. The biopsies
      with adequate cortical and medullary tissue (n = 23) were selected and medullary
      tissues were reviewed for rejection related lesions except intimal arteritis.
      Chronic damage was determined by image analysis depending on periodic acid
      methenamine silver (PAMS)-Masson trichrome (MT) staining. Medullary and cortical
      changes were compared. RESULTS: Interstitial inflammation and tubulitis were more
      frequent and severe in the cortex (p<0.001). Medullary tubulitis was associated
      with intimal arteritis (p = 0.003, r = 0.598). Medullary interstitial
      inflammation (n = 8) and tubulitis (n = 4) were associated with cortical
      borderline changes (n = 5) or allograft rejection (n = 3). The sensitivity,
      specificity, and positive and negative predictive values of medullary
      inflammatory changes in predicting cortical allograft rejection were 43%, 69%,
      37%, and 73%, respectively. A significant association was observed between
      medullary MT-SAP and cortical PAMS-SAP values (p = 0.02, R(2) = 0.23).
      CONCLUSIONS: Acute rejection related lesions are more common and severe in the
      cortex, and the renal medulla does not sufficiently reflect cortical rejection.
      The positive and negative predictive values of medullary changes for allograft
      rejection are low, and medullary inflammation is not a reliable indicator of
      allograft rejection. Increased medullary fibrosis is correlated with chronic
      cortical damage.

PMID- 16461570
TI  - Can the laboratory affect the investigation and diagnosis of primary biliary
      cirrhosis?
AB  - BACKGROUND: Primary biliary cirrhosis (PBC) is an autoimmune liver disease
      characterised by the presence of various laboratory abnormalities but the precise
      role of laboratory staff in initiating clinical referral and subsequent biopsy is
      not clear. OBJECTIVE: To examine the impact of laboratory abnormalities in the
      investigation of PBC. METHODS: In a retrospective study of laboratory results
      over nine years from 1996, computer records were reviewed to identify how many
      referrals for biopsy were initiated and subsequent diagnoses made as a result of
      clinical signs, raised serum alkaline phosphatase activity (ALP), raised IgM
      concentration, or positive mitochondrial antibodies accompanied by a clinical
      comment from the laboratory suggesting further action. RESULTS: 22 diagnoses of
      PBC were confirmed by histopathology. Eleven had high ALP activity which had
      follow up tests initiated by the laboratory (mitochondrial antibodies or IgM or
      both) and a comment added suggesting further investigation into the possibility
      of PBC. Seven had abnormal liver antibodies and one had a high polyclonal IgM
      concentration which prompted the relevant follow on testing and comments. One had
      an earlier diagnosis made on serological/clinical grounds and the biopsy was a
      confirmatory measure. One had no liver related antibodies. One had a request by
      laboratory staff for follow on tests but these were not asked for in subsequent
      samples by the requesting clinician. CONCLUSIONS: There is a positive role for
      laboratory staff in the diagnosis of PBC. Unexplained rises in ALP activity,
      positive mitochondrial antibodies, or raised IgM concentrations should be
      investigated more fully by laboratory staff and advice given to prompt a clinical
      referral for review and biopsy.

PMID- 16461571
TI  - Pitfalls in immunohistochemical assessment of EGFR expression in soft tissue
      sarcomas.
AB  - BACKGROUND: New targeted cancer treatments acting against growth factor receptors
      such as the epidermal growth factor receptor (EGFR) necessitate selecting
      patients for treatment with these drugs. Besides carcinomas, soft tissue sarcomas
      (STS) express EGFR and might thereby be a promising target for this new
      therapeutic strategy. OBJECTIVE: To test and compare different EGFR antibodies to
      determine the frequency of EGFR expression in STS. METHODS: 302 consecutive
      specimens of STS were examined using the tissue microarray technique. EGFR
      expression levels were assessed by immunohistochemistry using five different
      commercially available antibodies. Gene amplification status was measured by
      fluorescence in situ hybridisation (FISH). Immunoreactivity and amplification
      status were correlated with clinicopathological features and follow up data
      available in 163 cases. RESULTS: EGFR expression frequency ranged between 0.3%
      and 52.9%, depending on the antibody and scoring method used. In all, 3.5% of the
      tumours showed egfr gene amplification by FISH, which correlated with EGFR
      expression for three antibodies. Only one antibody had independent prognostic
      value in multivariate analysis and correlated with an unfavourable outcome; egfr
      gene amplification status showed no correlation with clinical features.
      CONCLUSIONS: Frequency of EGFR immunopositivity in STS strongly depends on the
      antibody used, and only one of five antibodies tested predicted an unfavourable
      clinical outcome. This indicates that choice of primary antibody and scoring
      system have a substantial impact on the determination of EGFR immunoreactivity.

PMID- 16461572
TI  - Frequent 7q gains in flow cytometric multiploid/hypertetraploid breast
      carcinomas: a study of chromosome imbalances by comparative genomic
      hybridisation.
AB  - OBJECTIVE: To investigate underlying genetic events associated with complex DNA
      ploidy breast carcinomas. METHODS: Screening for chromosome imbalances was
      carried out using comparative genomic hybridisation (CGH) in 14 frozen samples of
      tumour from a series of 13 breast cancer patients with multiploid (n = 11) and
      hypertetraploid (n = 2) tumours. They had previously been analysed by DNA flow
      cytometry and also assessed immunohistochemically for p53 tissue expression.
      Ploidy status was determined on frozen samples using the Multicycle software
      program. RESULTS: The total number of copy gains (n = 242) was significantly
      greater than the number of copy losses (n = 51). The mean (SD) number of gains
      per sample was 17.3 (5.7), and of losses, 3.6 (4.2) (p = 0.0001). Gains of
      chromosomal regions at 1q (14/14; 100%), 7q (12/14; 85.7%), and 3q (11/14;
      78.6%), as well as 1p, 2q, 5p, 8q, and 13q (10/14; 71.4%) were the most frequent
      aberrations in this series. Losses were most commonly found on 17p (5/14; 35.7%).
      Three patients dying of the disease had tumours with high level amplifications at
      1q12-qter, 3q22-q25, and 8q22-q23 regions. Six cases had p53 overexpression, of
      whom four showed 12q gains and two showed 17p losses. CONCLUSIONS: There is a
      very high incidence of genetic aberrations, mainly related to chromosomal gains,
      in this subgroup of aneuploid breast cancer patients, associated with a poor
      clinical outcome. The 7q locus, not previously reported as showing frequent
      changes in breast cancer, was found to be a potential site for some candidate
      oncogenes.

PMID- 16461573
TI  - Integrated treatment and implications for off-medication periods.

PMID- 16461574
TI  - Rationale and parameters for medication-free research in psychosis.

PMID- 16461575
TI  - Scientific and consumer models of recovery in schizophrenia: concordance,
      contrasts, and implications.
AB  - Schizophrenia has traditionally been viewed as a chronic condition with a very
      pessimistic outlook, but that assumption may not be valid. There has been a
      growing consumer movement among people with schizophrenia that has challenged
      both the traditional perspective on the course of illness and the associated
      assumptions about the possibility of people with the illness living a productive
      and satisfying life. This new conception of the illness is supported by long-term
      studies that suggest that as much as 50% of people with the illness have good
      outcomes. There has also been a change in political and public health
      perspectives of the illness, stimulated in part by the President's New Freedom
      Commission on Mental Health. The purpose of this article is to provide an
      overview of some key themes about the recovery concept, as applied to
      schizophrenia. The article will address 3 questions: (1) What is recovery? (2) Is
      recovery possible? and (3) What are the implications of a recovery model for a
      scientific approach to treatment (ie, the use of evidence-based practices)?
      Scientific and consumer models of recovery are described, and commonalities and
      differences are discussed. Priorities for future research are suggested.

PMID- 16461576
TI  - Peer support among adults with serious mental illness: a report from the field.
AB  - Peer support is based on the belief that people who have faced, endured, and
      overcome adversity can offer useful support, encouragement, hope, and perhaps
      mentorship to others facing similar situations. While this belief is well
      accepted for many conditions, such as addiction, trauma, or cancer, stigma and
      stereotypes about mental illness have impeded attempts on the part of people in
      recovery to offer such supports within the mental health system. Beginning in the
      early 1990s with programs that deployed people with mental illness to provide
      conventional services such as case management, opportunities for the provision
      and receipt of peer support within the mental health system have proliferated
      rapidly across the country as part of the emerging recovery movement. This
      article defines peer support as a form of mental health care and reviews data
      from 4 randomized controlled trials, which demonstrated few differences between
      the outcomes of conventional care when provided by peers versus non-peers. We
      then consider what, if any, unique contributions can be made by virtue of a
      person's history of serious mental illness and recovery and review beginning
      efforts to identify and evaluate these potential valued-added components of care.
      We conclude by suggesting that peer support is still early in its development as
      a form of mental health service provision and encourage further exploration and
      evaluation of this promising, if yet unproven, practice.

PMID- 16461578
TI  - The free NADH concentration is kept constant in plant mitochondria under
      different metabolic conditions.
AB  - The reduced coenzyme NADH plays a central role in mitochondrial respiratory
      metabolism. However, reports on the amount of free NADH in mitochondria are
      sparse and contradictory. We first determined the emission spectrum of NADH bound
      to proteins using isothermal titration calorimetry combined with fluorescence
      spectroscopy. The NADH content of actively respiring mitochondria (from potato
      tubers [Solanum tuberosum cv Bintje]) in different metabolic states was then
      measured by spectral decomposition analysis of fluorescence emission spectra.
      Most of the mitochondrial NADH is bound to proteins, and the amount is low in
      state 3 (substrate + ADP present) and high in state 2 (only substrate present)
      and state 4 (substrate + ATP). By contrast, the amount of free NADH is low but
      relatively constant, even increasing a little in state 3. Using modeling, we show
      that these results can be explained by a 2.5- to 3-fold weaker average binding of
      NADH to mitochondrial protein in state 3 compared with state 4. This indicates
      that there is a specific mechanism for free NADH homeostasis and that the
      concentration of free NADH in the mitochondrial matrix per se does not play a
      regulatory role in mitochondrial metabolism. These findings have far-reaching
      consequences for the interpretation of cellular metabolism.

PMID- 16461579
TI  - Analysis of the transcription factor WUSCHEL and its functional homologue in
      Antirrhinum reveals a potential mechanism for their roles in meristem
      maintenance.
AB  - One of the most significant features of plant development is the way in which it
      can be elaborated and modulated throughout the life of the plant, an ability that
      is conferred by meristems. The Arabidopsis thaliana WUSCHEL gene (WUS), which
      encodes a homeodomain transcription factor, is required to maintain the stem
      cells in the shoot apical meristem in an undifferentiated state. The mechanism by
      which WUS prevents the differentiation of stem cells is unknown. We have
      characterized a meristem maintenance mutant in Antirrhinum majus and shown that
      it arises from a defect in the WUS orthologue ROSULATA (ROA). Detailed
      characterization of a semidominant roa allele revealed an essential role for the
      conserved C-terminal domain. Expression of either ROA or WUS lacking this domain
      causes a failure of meristem maintenance. The conserved domain mediates an
      interaction between WUS and two members of a small family of corepressor-like
      proteins in Arabidopsis. Our results suggest that WUS functions by recruiting
      transcriptional corepressors to repress target genes that promote
      differentiation, thereby ensuring stem cell maintenance.

PMID- 16461580
TI  - The chimeric Arabidopsis CYCLIC NUCLEOTIDE-GATED ION CHANNEL11/12 activates
      multiple pathogen resistance responses.
AB  - To investigate the resistance signaling pathways activated by pathogen infection,
      we previously identified the Arabidopsis thaliana mutant constitutive expresser
      of PR genes22 (cpr22), which displays constitutive activation of multiple defense
      responses. Here, we identify the cpr22 mutation as a 3-kb deletion that fuses two
      cyclic nucleotide-gated ion channel (ATCNGC)-encoding genes, ATCNGC11 and
      ATCNGC12, to generate a novel chimeric gene, ATCNGC11/12. Genetic, molecular, and
      complementation analyses suggest that ATCNGC11/12, as well as ATCNGC11 and
      ATCNGC12, form functional cAMP-activated ATCNGCs and that the phenotype conferred
      by cpr22 is attributable to the expression of ATCNGC11/12. However, because
      overexpression of ATCNGC12, but not ATCNGC11, suppressed the phenotype conferred
      by cpr22, the development of this phenotype appears to be regulated by the ratio
      between ATCNGC11/12 and ATCNGC12. Analysis of knockout lines revealed that both
      ATCNGC11 and ATCNGC12 are positive mediators of resistance against an avirulent
      biotype of Hyaloperonospora parasitica. Through epistatic analyses, cpr22
      mediated enhanced resistance to pathogens was found to require NDR1-dependent and
      EDS1/PAD4-dependent pathways. In striking contrast, none of these pathways was
      required for cpr22-induced salicylic acid accumulation or PR-1 gene expression.
      These results demonstrate that NDR1, EDS1, and PAD4 mediate other resistance
      signaling function(s) in addition to salicylic acid and pathogenesis-related
      protein accumulation. Moreover, the requirement for both NDR1-dependent and
      EDS1/PAD4-dependent pathways for cpr22-mediated resistance suggests that these
      pathways are cross-regulated.

PMID- 16461577
TI  - Transcriptome profiling, molecular biological, and physiological studies reveal a
      major role for ethylene in cotton fiber cell elongation.
AB  - Upland cotton (Gossypium hirsutum) produces the most widely used natural fibers,
      yet the regulatory mechanisms governing fiber cell elongation are not well
      understood. Through sequencing of a cotton fiber cDNA library and subsequent
      microarray analysis, we found that ethylene biosynthesis is one of the most
      significantly upregulated biochemical pathways during fiber elongation. The 1
      Aminocyclopropane-1-Carboxylic Acid Oxidase1-3 (ACO1-3) genes responsible for
      ethylene production were expressed at significantly higher levels during this
      growth stage. The amount of ethylene released from cultured ovules correlated
      with ACO expression and the rate of fiber growth. Exogenously applied ethylene
      promoted robust fiber cell expansion, whereas its biosynthetic inhibitor l-(2
      aminoethoxyvinyl)-glycine (AVG) specifically suppressed fiber growth. The
      brassinosteroid (BR) biosynthetic pathway was modestly upregulated during this
      growth stage, and treatment with BR or its biosynthetic inhibitor brassinazole
      (BRZ) also promoted or inhibited, respectively, fiber growth. However, the effect
      of ethylene treatment was much stronger than that of BR, and the inhibitory
      effect of BRZ on fiber cells could be overcome by ethylene, but the AVG effect
      was much less reversed by BR. These results indicate that ethylene plays a major
      role in promoting cotton fiber elongation. Furthermore, ethylene may promote cell
      elongation by increasing the expression of sucrose synthase, tubulin, and
      expansin genes.

PMID- 16461581
TI  - Blind homologous R2R3 Myb genes control the pattern of lateral meristem
      initiation in Arabidopsis.
AB  - In seed plants, shoot branching is initiated during postembryonic development by
      the formation of secondary meristems. These new meristems, which are established
      between the stem and leaf primordia, develop into vegetative branches or flowers.
      Thus, the number of axillary meristems has a major impact on plant architecture
      and reproductive success. This study describes the genetic control of axillary
      meristem formation in Arabidopsis thaliana by a group of three R2R3 Myb genes,
      which are homologous to the tomato (Solanum lycopersicum) Blind gene and were
      designated REGULATORS OF AXILLARY MERISTEMS (RAX). rax mutants show new
      phenotypes that are characterized by defects in lateral bud formation in
      overlapping zones along the shoot axis. RAX genes are partially redundant in
      function and allow a fine-tuning of secondary axis formation. As revealed by
      monitoring of SHOOT MERISTEMLESS transcript accumulation, the RAX genes control a
      very early step of axillary meristem initiation. The RAX1 and RAX3 expression
      domains specifically mark a cell group in the center of the leaf axil from which
      the axillary meristem develops. Double mutant combinations of lateral suppressor
      and rax1-3 as well as expression studies suggest that at least two pathways
      control the initiation of axillary meristems in Arabidopsis.

PMID- 16461582
TI  - Vacuolar H+-ATPase activity is required for endocytic and secretory trafficking
      in Arabidopsis.
AB  - In eukaryotic cells, compartments of the highly dynamic endomembrane system are
      acidified to varying degrees by the activity of vacuolar H(+)-ATPases (V
      ATPases). In the Arabidopsis thaliana genome, most V-ATPase subunits are encoded
      by small gene families, thus offering potential for a multitude of enzyme
      complexes with different kinetic properties and localizations. We have determined
      the subcellular localization of the three Arabidopsis isoforms of the membrane
      integral V-ATPase subunit VHA-a. Colocalization experiments as well as immunogold
      labeling showed that VHA-a1 is preferentially found in the trans-Golgi network
      (TGN), the main sorting compartment of the secretory pathway. Uptake experiments
      with the endocytic tracer FM4-64 revealed rapid colocalization with VHA-a1,
      indicating that the TGN may act as an early endosomal compartment. Concanamycin
      A, a specific V-ATPase inhibitor, blocks the endocytic transport of FM4-64 to the
      tonoplast, causes the accumulation of FM4-64 together with newly synthesized
      plasma membrane proteins, and interferes with the formation of brefeldin A
      compartments. Furthermore, nascent cell plates are rapidly stained by FM4-64,
      indicating that endocytosed material is redirected into the secretory flow after
      reaching the TGN. Together, our results suggest the convergence of the early
      endocytic and secretory trafficking pathways in the TGN.

PMID- 16461583
TI  - High-resolution single-copy gene fluorescence in situ hybridization and its use
      in the construction of a cytogenetic map of maize chromosome 9.
AB  - High-resolution cytogenetic maps provide important biological information on
      genome organization and function, as they correlate genetic distance with
      cytological structures, and are an invaluable complement to physical sequence
      data. The most direct way to generate a cytogenetic map is to localize
      genetically mapped genes onto chromosomes by fluorescence in situ hybridization
      (FISH). Detection of single-copy genes on plant chromosomes has been difficult.
      In this study, we developed a squash FISH procedure allowing successful detection
      of single-copy genes on maize (Zea mays) pachytene chromosomes. Using this
      method, the shortest probe that can be detected is 3.1 kb, and two sequences
      separated by approximately 100 kb can be resolved. To show the robust nature of
      this protocol, we localized nine genetically mapped single-copy genes on
      chromosome 9 in one FISH experiment. Integration of existing information from
      genetic maps and the BAC contig-based physical map with the cytological structure
      of chromosome 9 provides a comprehensive cross-referenced cytogenetic map and
      shows the dramatic reduction of recombination in the pericentromeric
      heterochromatic region. To establish a feasible mapping system for maize, we also
      developed a probe cocktail for unambiguous identification of the 10 maize
      pachytene chromosomes. These results provide a starting point toward constructing
      a high-resolution integrated cytogenetic map of maize.

PMID- 16461584
TI  - Within-species flagellin polymorphism in Xanthomonas campestris pv campestris and
      its impact on elicitation of Arabidopsis FLAGELLIN SENSING2-dependent defenses.
AB  - Bacterial flagellins have been portrayed as a relatively invariant pathogen
      associated molecular pattern. We have found within-species, within-pathovar
      variation for defense-eliciting activity of flagellins among Xanthomonas
      campestris pv campestris (Xcc) strains. Arabidopsis thaliana FLAGELLIN SENSING2
      (FLS2), a transmembrane leucine-rich repeat kinase, confers flagellin
      responsiveness. The flg22 region was the only Xcc flagellin region responsible
      for detectable elicitation of Arabidopsis defense responses. A Val-43/Asp
      polymorphism determined the eliciting/noneliciting nature of Xcc flagellins
      (structural gene fliC). Arabidopsis detected flagellins carrying Asp-43 or Asn-43
      but not Val-43 or Ala-43, and it responded minimally for Glu-43. Wild-type Xcc
      strains carrying nonrecognized flagellin were more virulent than those carrying a
      recognized flagellin when infiltrated into Arabidopsis leaf mesophyll, but this
      correlation was misleading. Isogenic Xcc fliC gene replacement strains expressing
      eliciting or noneliciting flagellins grew similarly, both in leaf mesophyll and
      in hydathode/vascular colonization assays. The plant FLS2 genotype also had no
      detectable effect on disease outcome when previously untreated plants were
      infected by Xcc. However, resistance against Xcc was enhanced if FLS2-dependent
      responses were elicited 1 d before Xcc infection. Prior immunization was not
      required for FLS2-dependent restriction of Pseudomonas syringae pv tomato. We
      conclude that plant immune systems do not uniformly detect all flagellins of a
      particular pathogen species and that Xcc can evade Arabidopsis FLS2-mediated
      defenses unless the FLS2 system has been activated by previous infections.

PMID- 16461585
TI  - PLASTOCHRON2 regulates leaf initiation and maturation in rice.
AB  - In higher plants, leaves initiate in constant spatial and temporal patterns.
      Although the pattern of leaf initiation is a key element of plant shoot
      architecture, little is known about how the time interval between initiation
      events, termed plastochron, is regulated. Here, we present a detailed analysis of
      plastochron2 (pla2), a rice (Oryza sativa) mutant that exhibits shortened
      plastochron and precocious maturation of leaves during the vegetative phase and
      ectopic shoot formation during the reproductive phase. The corresponding PLA2
      gene is revealed to be an orthologue of terminal ear1, a maize (Zea mays) gene
      that encodes a MEI2-like RNA binding protein. PLA2 is expressed predominantly in
      young leaf primordia. We show that PLA2 normally acts to retard the rate of leaf
      maturation but does so independently of PLA1, which encodes a member of the P450
      family. Based on these analyses, we propose a model in which plastochron is
      determined by signals from immature leaves that act non-cell-autonomously in the
      shoot apical meristem to inhibit the initiation of new leaves.

PMID- 16461586
TI  - Modafinil [2-[(diphenylmethyl)sulfinyl]acetamide] and circadian rhythms in syrian
      hamsters: assessment of the chronobiotic potential of a novel alerting compound.
AB  - In Syrian hamsters, behavioral procedures for inducing arousal (e.g., running in
      a novel wheel or gentle handling) can shift circadian rhythms when applied during
      the usual sleep period ("subjective day") and can attenuate phase shifts to light
      during the active period ("subjective night"). This raises the possibility that
      drugs that affect behavioral state may have "chronobiotic" potential. We
      characterized the effects of modafinil (2-[(diphenylmethyl)sulfinyl]acetamide),
      an atypical alerting compound, on circadian rhythms in male Syrian hamsters.
      Electroencephalogram recordings and video observations confirmed that modafinil
      dose dependently increases wakefulness at the expense of slow-wave and
      paradoxical sleep with no increase in locomotor activity per unit of time awake.
      Despite inducing arousal, modafinil at these doses (150 or 300 mg/kg),
      administered in the subjective day or early or late in the subjective night, did
      not perturb circadian phase. Modafinil (300 mg/kg) also had no effect on phase
      shifts to light exposure either early or late in the night and did not alter the
      size of phase shifts induced by running in a novel wheel for 3 h during the mid
      day. Modafinil (300 mg/kg) did, however, decrease by approximately 50% the amount
      of novel wheel-stimulated running, moving leftward the dose-response relation
      between wheel revolutions and shift magnitude. These results indicate that, in
      Syrian hamsters, modafinil alone has no significant chronobiotic efficacy.
      Nevertheless, this agent may increase the sensitivity of the circadian pacemaker
      to nonphotic stimuli and may thus have some potential as a tool for promoting
      clock resetting in combination with behavioral strategies.

PMID- 16461587
TI  - Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B)
      receptors in mice.
AB  - A correlation between high plasma serotonin levels and total pulmonary resistance
      was reported in more than 80% of pulmonary hypertensive patients. When submitted
      to chronic hypoxia (10% O(2) for more than 3 weeks), wild-type mice develop lung
      vascular remodeling and pulmonary hypertension. We previously reported that, in
      contrast, the development of these hypoxia-dependent alterations is totally
      abolished in mice with permanent (genetic) or transient (pharmacologic)
      inactivation of the serotonin 5-hydroxytryptamine (5-HT)(2B) receptor. In the
      present study, we asked whether 5-HT(2B) receptors could be involved in the
      control of plasma serotonin levels. Further investigating the chronic hypoxic
      mouse model of pulmonary hypertension, we first show that in wild-type mice,
      plasma serotonin levels and 5-HT(2B) receptors expression were significantly
      increased after chronic exposure to hypoxia. This increase appeared before
      significant changes in remodeling factors could be detected and persisted when
      the pathology was established. Conversely, in mice with either genetically or
      pharmacologically inactive 5-HT(2B) receptors, plasma serotonin levels were not
      modified by chronic hypoxia. We then confirmed that 5-HT(2B) receptors can
      control plasma serotonin levels by providing in vivo evidence that an acute
      agonist stimulation of 5-HT(2B) receptor triggers a transient increase in plasma
      serotonin that is serotonin transporter dependent and blocked by 5-HT(2B)
      receptor-selective antagonist or genetic ablation. Our data support the notion
      that a 5-HT(2B) receptor-dependent regulation of serotonin uptake is implicated
      in the control of plasma serotonin levels.

PMID- 16461588
TI  - Therapeutic time window and dose dependence of neuroprotective effects of sodium
      orthovanadate following transient middle cerebral artery occlusion in rats.
AB  - Vanadium is widely distributed in the environment and exhibits various biological
      and physiological effects in the human body. We previously documented the
      neuroprotective effect of sodium orthovanadate (SOV) against in rodents i.v.
      injected with 2 ml/kg 50 mM SOV just after the induction of middle cerebral
      artery occlusion (MCAO; 0 min post-MCAO). To evaluate its potential clinical use,
      we determined here therapeutic time window (0, 45, and 90 min post-MCAO) and the
      neuroprotective dose (2 ml/kg, 12.5, 25, 37.5, and 50 mM) of SOV in rats. A
      single injection of 50 mM SOV at 0 or 45 min post-MCAO produced similar
      neuroprotective effects, and even 50 mM delivered 90 min post-MCAO exerted
      significant neuroprotection. Although the maximal neuroprotective effect was
      obtained at 50 mM SOV, 25 mM injected once and 12.5 mM delivered at 0 and 45 min
      post-MCAO significantly reduced the infarct volume. We also documented that SOV
      treatment ameliorates ischemic neuronal cell injury via the activation of both
      protein kinase B (Akt) and extracellular signal-regulated kinase (ERK), inhibits
      serum glucose, and elicits the gradual recovery of regional cerebral blood flow
      (rCBF) after transient MCAO in rats. To elucidate the important factor(s)
      involved in the neuronal protection afforded by SOV, we measured Akt and ERK
      activity, physiological parameters, blood glucose levels, and rCBF following
      various SOV treatments. In conclusion, Akt activation was the most important
      factor in SOV-induced neuroprotection; ERK activation, the gradual recovery of
      rCBF, and decreased blood glucose were weak contributors.

PMID- 16461589
TI  - Differential regulation of the cell-surface targeting and function of beta- and
      alpha1-adrenergic receptors by Rab1 GTPase in cardiac myocytes.
AB  - The molecular mechanism underlying the export from the endoplasmic reticulum (ER)
      to the cell surface and its role in the regulation of signaling of adrenergic
      receptors (ARs) remain largely unknown. In this report, we determined the role of
      Rab1, a Ras-like GTPase that coordinates protein transport specifically from the
      ER to the Golgi, in the cell surface targeting and function of endogenous beta-
      and alpha1-ARs in neonatal rat ventricular myocytes. Adenovirus-driven expression
      of Rab1 into myocytes selectively increased the cell-surface number of alpha1-AR,
      but not beta-AR, whereas the dominant-negative mutant Rab1N124I significantly
      reduced the cell-surface expression of beta-AR and alpha1-AR. Brefeldin A
      inhibited beta-AR and alpha1-AR export and antagonized the Rab1 effect on alpha1
      AR expression. Manipulation of Rab1 function similarly influenced the transport
      of alpha1A- and alpha1B-ARs as well as beta1- and beta2-ARs. Fluorescent
      microscopy analysis demonstrated that expression of Rab1N124I and Rab1 small
      interfering RNA induced a marked accumulation of GFP-tagged beta2-AR and alpha1B
      AR in the ER. Consistent with the effects on receptor cell-surface targeting,
      Rab1 selectively enhanced ERK1/2 activation and hypertrophic growth in response
      to the alpha1-AR agonist phenylephrine but not to the beta-AR agonist
      isoproterenol. Rab1N124I inhibited both agonist-mediated ERK1/2 activation and
      hypertrophic growth in neonatal myocytes. These results demonstrate that the cell
      surface targeting and signaling of beta- and alpha1-ARs require Rab1 and are
      differentially modulated by augmentation of Rab1 function. Our data provide
      strong evidence implicating the ER-to-Golgi traffic as a site for selective
      manipulation of distinct AR function in cardiac myocytes.

PMID- 16461590
TI  - Congenital syphilis in the United Kingdom.

PMID- 16461592
TI  - Still waiting: poor access to sexual health services in the UK.

PMID- 16461593
TI  - Monitoring the effectiveness of HIV and STI prevention initiatives in England,
      Wales, and Northern Ireland: where are we now?
AB  - Primary and secondary prevention are essential components of the response to HIV
      and sexually transmitted infections (STIs). We present findings from nationally
      implemented HIV/STI prevention interventions. In 2003, of those attending STI
      clinics at least 64% of men who have sex with men (MSM) and 55% of heterosexuals
      accepted a confidential HIV test; 88% of all HIV infections in women giving birth
      in England were diagnosed before delivery; 85% of MSM eligible for hepatitis B
      vaccination received a first dose of vaccine at their first STI clinic
      attendance; 74% of STI clinic attendees for emergency appointments, and 20% of
      those for routine appointments were seen within 48 hours of initiating an
      appointment; the National Chlamydia Screening Programme in England found a
      positivity of 10% and 13% among young asymptomatic women and men, respectively.
      Prevention initiatives have seen recent successes in limiting further HIV/STI
      transmission. However, more work is required if current levels of transmission
      are to be reduced.

PMID- 16461594
TI  - HIV and syphilis in migrant workers in eastern China.
AB  - OBJECTIVE: To measure the prevalence of HIV and syphilis in migrant and urban
      workers in eastern China, and to determine their knowledge and attitudes towards
      HIV. METHODS: A cross sectional survey involving dried blood spot testing and
      self completion questionnaires. Migrants and urban workers in 39 work units in
      two districts of Hangzhou, Zhejiang Province, were recruited. Respondents
      completed a questionnaire about knowledge and attitudes towards HIV. Testing for
      antibodies to HIV-1 and syphilis was carried out on dried blood spots using a
      gelatin particle agglutination technique. RESULTS: Data were obtained from 4148
      migrants and 2197 urban workers. There were no HIV infections detected in either
      the migrant or urban populations. Syphilis was detected, but the prevalence was
      not significantly different between urban workers (0.68%, 95% CI: 0.35 to 1.02)
      and migrant workers (0.48%, 95% CI 0.26 to 0.66, p = 0.07). 36% of the migrants
      had migrated with a partner, and 7% had also migrated with children. Urban
      workers were consistently more knowledgeable than migrants about HIV, but
      knowledge of the major modes of transmission was good in both groups. Traditional
      attitudes to sexual behaviour were still pervasive in both groups and attitudes
      towards individuals with HIV were generally intolerant. The use of sex workers
      appears rare and no more common in migrants than urban workers. CONCLUSION: At
      present HIV is probably not spreading in the internal migrant population in
      eastern China. Syphilis is a problem in both the migrant and urban populations.
      The tendency to migrate with partners makes migrants relatively low risk for
      engaging in casual sex.

PMID- 16461595
TI  - Factors associated with heterosexual transmission of HIV to individuals without a
      major risk within England, Wales, and Northern Ireland: a comparison with
      national probability surveys.
AB  - OBJECTIVE: To compare the prevalence of HIV risk behaviours reported by
      heterosexuals without major risks for HIV acquisition diagnosed with HIV in
      England, Wales, and Northern Ireland, with those of the heterosexual general
      population. METHODS: Demographic and sexual behaviour data for heterosexuals
      (without major risks for HIV) aged 16-44 from the British National Surveys of
      Sexual Attitudes and Lifestyles in 1990 and 2000 were compared to 139 HIV
      infected individuals without major risks for HIV aged 16+ at diagnosis,
      interviewed between December 1987 and March 2003. Comparisons were made overall
      and separately for the early and late 1990s. RESULTS: HIV infected heterosexual
      men without major risks were significantly more likely to report first
      heterosexual intercourse before age 16 (adjusted odds ratio (AOR): 2.75; 95%
      confidence interval (CI),1.65 to 4.57), while both HIV infected heterosexual men
      and women reported greater partner numbers (AOR: men 2.44; CI, 1.4 to 4.05; AOR
      women 2.17; CI, 1.28 to 3.66) and never using condoms (AOR: men 7.97; CI,4.78 to
      13.3; AOR women 3.95; CI, 2.30 to 6.80) than the heterosexual general population.
      There is evidence to suggest that the two groups were more similar in their
      reporting of partner numbers in the late 1990s relative to the early 1990s.
      CONCLUSION: Heterosexual HIV infected individuals without major risks for HIV
      acquisition in England, Wales, and Northern Ireland are significantly more likely
      to report high risk sexual behaviours relative to the British heterosexual
      general population. However, these differences may have decreased over time, at
      least for the number of partners. Effective sexual health promotion, including
      the continued promotion of condom use, would impact on the rising rates of STI
      diagnoses and also prevent HIV transmission among the heterosexual general
      population.

PMID- 16461596
TI  - Is screening for sexually transmitted infections in men who have sex with men who
      receive non-occupational HIV post-exposure prophylaxis worthwhile?
AB  - BACKGROUND/AIMS: Non-occupational HIV post-exposure prophylaxis (NPEP) is
      routinely prescribed after high risk sexual exposure. This provides an
      opportunity to screen and treat individuals at risk of concurrent sexually
      transmitted infections (STI). The aim of this study was to assess the efficacy of
      an STI screening programme in individuals receiving NPEP. METHODS: STI screens
      were offered to all individuals receiving NPEP from March 2001 to May 2004.
      Screen results were compared to type of sexual exposure and baseline patient
      characteristics. RESULTS: A total of 253 subjects were screened, representing 85%
      of the target population. All were men who have sex with men (MSM). Common
      exposure risks were receptive anal intercourse (RAI) in 61% and insertive anal
      intercourse (IAI) in 33%. 32 (13%) individuals had one or more STI. The most
      common STIs were rectal infections with Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) in 11 (4.5%) and six (2.5%) individuals, respectively. Subjects
      with rectal CT were significantly more likely to be co-infected with rectal NG
      (p<0.001). There was no association between the presence of a rectal STI and age
      or exposure risk. Only six (19%) individuals with an STI were symptomatic at
      screening. CONCLUSION: In this cohort of MSM receiving NPEP, high rates of
      concomitant STIs are observed highlighting the importance of STI screening in
      this setting.

PMID- 16461597
TI  - What is the impact of change in diagnostic test method on surveillance data
      trends in Chlamydia trachomatis infection?
AB  - OBJECTIVE: To describe the impact of change from culture to more sensitive
      nucleic acid amplification testing (NAAT) tests on the detection of Chlamydia
      trachomatis in a genitourinary medicine (GUM) clinic population. METHODS: Data
      were collected between January 1992 and December 2003 on results of C trachomatis
      tests on male and female attenders at the Lothian GUM clinic (n = 81 590).
      Routine diagnosis switched from culture to NAAT methods in September 1998.
      Association of test result with age, sex, year of test, and test type was
      analysed using logistic regression. RESULTS: 6.1% (95% CI: 5.7% to 6.5%) of women
      and 7.1% of men (95% CI: 6.7% to 7.5%) tested positive with culture and 9.9% of
      women (95% CI: 9.4% to 10.3%) and 11.1% of men (95% CI: 10.7% to 11.5%) tested
      positive with NAATs. This corresponds to a 56% increase for men (95% CI: 47% to
      66%) and 62% for women (95% CI: 50% to 67%). Logistic regression showed that a
      positive test result was strongly associated with test type with or without
      adjustment for year of test, sex, and young age. CONCLUSIONS: The significant
      increase in chlamydial infections detected following a change from culture to
      NAATs has important implications for interpretation of trends ascertained from
      surveillance data. Not all of this can be a direct effect of enhanced sensitivity
      and there may be indirect effects that improve ascertainment of existing
      infections. As more laboratories switch to NAATs similar patterns of stepwise
      increases in positive results are expected and trend analysis based on such
      surveillance data might thus show an artefactual rise in chlamydia infection
      rates. Accumulated surveillance data should therefore include timing of
      introduction of NAAT, so as to take account of under-ascertainment by previous
      methods.

PMID- 16461598
TI  - Human papillomavirus in men: comparison of different genital sites.
AB  - OBJECTIVE: To elucidate which anatomical sites need to be sampled to detect human
      papillomavirus (HPV) infection in the lower male genital tract. METHOD: In an HPV
      survey of Mexican soldiers (median age 24 years; range 16-50 years), a cell
      sample from 2 cm deep into the distal urethra (group 1; n = 168 men), or 0.5 cm
      deep into the meatus urethralis (group 2; n = 414 men) was collected, along with
      a sample from the external genitalia. The different samples were tested for 27
      HPV types using a polymerase chain reaction based strip assay. RESULTS: HPV DNA
      was detected more frequently in external genitalia samples (46.4%) than in the
      urethra (20.8%) or meatus samples (12.1%). Lack of samples from the urethra or
      meatus would have led to 5.1% and 1.5% false HPV negative results, respectively.
      The most frequently detected high risk HPV types (HPV 59, 52, 51, and 16) were
      similar in different sites, whereas low risk types were found rarely in urethra
      samples. CONCLUSIONS: The addition of cell samples from the meatus to those from
      external genitalia contributed negligibly to the evaluation of the prevalence of
      HPV in men. HPV detection was slightly improved by the addition of urethra
      samples, but the gain may not justify the discomfort of the procedure in large
      epidemiological studies.

PMID- 16461599
TI  - The significance of voiding interval before testing urine samples for Chlamydia
      trachomatis in men.
AB  - OBJECTIVE: To investigate the effect of time since last urination on chlamydial
      positivity rates in men. METHODS: Prospective study on men attending a
      genitourinary medicine clinic who were asked for the last time of their urination
      before obtaining their urine sample for testing for Chlamydia trachomatis with
      the Cobas Amplicor polymerase chain reaction (PCR) assay. RESULTS: Of the total
      of 1649 men studied, 621 (37.6% (95% CI 35.3% to 39.9%)) had a voiding interval
      of less than 2 hours. There was no statistical evidence of a difference in the
      positivity rate of chlamydial infection among men with a voiding interval of less
      than 2 hours (106/621, 17.1%) and that of men with a voiding interval of 2 hours
      or longer (170/1028, 16.5%); difference in proportions 0.5% (95% CI to 3.2% to
      4.3%), p = 0.779. CONCLUSION: Voiding interval does not have a significant impact
      on the performance of the Cobas Amplicor PCR assay in men.

PMID- 16461600
TI  - The superiority of polymerase chain reaction over an amplified enzyme immunoassay
      for the detection of genital chlamydial infections.
AB  - BACKGROUND/OBJECTIVES: The polymer conjugate enhanced enzyme immunoassay (IDEIA)
      and Cobas Amplicor polymerase chain reaction Chlamydia trachomatis (CT) (Amplicor
      PCR) are two commonly used assays for the diagnosis of CT infection. The
      performance of these assays was compared for the diagnosis of genital CT
      infection among 1000 consecutive patients attending a genitourinary medicine
      (GUM) clinic. Confirmation of positive results and the clinical significance of
      the absence of cryptic plasmid in chlamydia on the diagnosis of infection by
      Amplicor PCR were also investigated. METHODS: IDEIA, Amplicor PCR, and two nested
      in-house PCR assays targeting cryptic plasmid and omp1 gene were performed on all
      samples. DNA from Amplicor PCR negative samples was pooled for in-house PCR
      assays. Each pool contained DNA from seven Amplicor PCR negative samples.
      RESULTS: Sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV), and efficiency of IDEIA in the diagnosis of genital CT
      infection were 80%, 97%, 80%, 97%, and 95%, respectively. Sensitivity,
      specificity, PPV, NPV and efficiency of Amplicor PCR were 99%, 98%, 89%, 100%,
      and 98%, respectively. 16 (11%) of 144 Amplicor PCR positive results were
      identified as false positive by in-house PCR assays. No isolate of plasmid free
      CT was detected among the study population. CONCLUSIONS: IDEIA should not be used
      for the diagnosis of CT infection because of its poor sensitivity. Although the
      analytic specificity of Amplicor PCR was 98%, because of the adverse medical,
      social, and psychological impact of false positive results for patients,
      confirmation of Amplicor PCR positive results by a different assay with
      comparable sensitivity is essential. Amplification assays targeting cryptic
      plasmid are appropriate for the diagnosis of genital CT infections.

PMID- 16461601
TI  - Laboratory diagnosis of Neisseria gonorrhoeae in St Petersburg, Russia:
      inventory, performance characteristics and recommended optimisations.
AB  - OBJECTIVES: To perform a comprehensive inventory of the number of samples,
      performance characteristics, and quality assurance of the laboratory diagnosis of
      Neisseria gonorrhoeae at five laboratories in St Petersburg and Leningradskaya
      Oblast, Russia, in 2004, and to recommend optimisations for an increased
      adherence to international evidence based recommendations of diagnostics.
      METHODS: Surveillance data were obtained with questionnaire and site visits. For
      evaluation of the culture media utilised at the laboratories, N gonorrhoeae
      reference strains (n = 29) were used. RESULTS: During 2004 the total numbers of N
      gonorrhoeae samples analysed at the five laboratories using microscopy of stained
      smears and culturing were 330 879 (407 positive) and 38 020 (420 positive),
      respectively. Four laboratories used a Russian non-selective culture medium-that
      is, Complegon, and one laboratory utilised Biocult-GC. Both media seemed
      suboptimal. Only two of the laboratories used any species confirmative assay.
      Antibiotic susceptibility testing of N gonorrhoeae was performed at only two of
      the laboratories and each year only occasional isolates were analysed. None of
      the laboratories comprised a complete laboratory quality assurance system.
      CONCLUSIONS: According to international recommendations, the diagnosis of N
      gonorrhoeae in St Petersburg and Leningradskaya Oblast, Russia, is suboptimal.
      More samples need to be analysed by culturing on a highly nutritious and
      selective medium and, furthermore, species confirmation and antibiotic
      susceptibility testing should be more frequently performed. In addition, the
      utilised methods for culturing and antibiotic susceptibility testing, including
      medium and interpretative criteria used, ought to be optimised, standardised, and
      quality assured using systematic internal and external quality controls.

PMID- 16461602
TI  - Supply and demand: estimating the real need for care while meeting the 48 hour
      waiting time target in a genitourinary medicine clinic by a closed appointment
      system.
AB  - AIM: To attempt to assess demand for access to sexual health services in a
      community where a "closed" appointment system operates in the local genitourinary
      medicine (GUM) clinic. SETTING: A large GUM clinic serving a provincial city in
      England. Appointments for new episodes are available only 1 or 2 days ahead.
      Service user complaints about repeated difficulty in getting through to book a
      visit prompted a review of all methods of access. METHODS: A prospective review
      of all calls received in the departmental telephone booking service was
      performed. Temporary extra staff manned a cascade sequence of telephone lines and
      recorded all calls and caller characteristics such as age and declaration of
      symptoms. All attempts to book an appointment in person, by written referral, or
      by telephone in a period of 5 working days were also logged. This total demand
      was compared with the actual capacity and maximum theoretical capacity of the
      clinic during the same time period. RESULTS: 626 appointments would be required
      in the working week to accommodate all patients within 48 hours of requesting to
      be seen. 84% of all calls requested a new appointment, and 77% all new
      appointment requests were by phone. There were 181 new appointments available;
      72% of those requesting an appointment could not be seen. The clinic was working
      at 103% capacity. To accommodate demand at this quiet time of the academic year,
      the GUM service would need to increase capacity by 3-4-fold. CONCLUSIONS: Closed
      appointment systems in GUM services may produce an apparent "improvement" in
      waiting times to 48 hours, but many callers are not able to book an appointment
      at all. Demand for GUM services outstrips capacity to an extent that internal
      efficiency savings cannot hope to address.

PMID- 16461603
TI  - Texting decreases the time to treatment for genital Chlamydia trachomatis
      infection.
AB  - OBJECTIVE: To assess the effectiveness of a text message result service within an
      inner London sexual health clinic. METHOD: Demographic data, diagnoses, and time
      to diagnosis and treatment were collected over a 6 month period for patients
      receiving text messages and a matched standard recall group. Data on messages
      sent, staff time, and cost in relation to result provision were collected.
      RESULTS: Over a 6 month period 952 text messages were sent. In the final month of
      analysis, 33.9% of all clinic results were provided by text, resulting in a
      saving of 46 hours of staff time per month. 49 messages requested that the
      patient return for treatment, 28 of these patients had untreated genital
      Chlamydia trachomatis (CT) infection. The mean number of days (SD) to diagnosis
      was significantly shorter in the text message group (TG) v the standard recall
      group (SG) (7.9 (3.6) v 11.2 (4.7), p <0.001). The median time to treatment was
      8.5 days (range 4-27 days) for the TG group v 15.0 (range 7-35) for SG, p =
      0.005. CONCLUSION: Patients with genital CT infection are diagnosed and receive
      treatment sooner since the introduction of a text message result service. The
      introduction of this service has resulted in a significant saving in staff time.

PMID- 16461604
TI  - Patients' attitudes to the presence of medical students in a genitourinary
      medicine clinic: a cross sectional survey.
AB  - OBJECTIVES: It is recommended that medical students learn how to take a sexual
      history and gain experience in genital examination, but patients' reluctance may
      make this difficult to achieve, especially for male students. METHODS: We
      performed a survey of 250 male and 250 female patients attending a genitourinary
      medicine (GUM) clinic to determine their attitudes towards the involvement of
      medical students during their visit. Data were collected on the patients' age,
      ethnic origin, parity, number of visits to the clinic, and the sex of the
      student. RESULTS: 92.8% of women and 79.2% of men participated. Younger women and
      men, those visiting the clinic for the first time, and women with no children
      were less likely to accept a student of either sex to take their history or
      observe their examination. Women were less likely than men to accept students of
      either sex to take their sexual history or be present during their examination,
      but were more likely than men to accept only same sex students. CONCLUSIONS:
      There was a high level of acceptability for the involvement of medical students;
      only 12.5% of women and 15% of men declined any medical student participation.
      Older women with children, and older men, were more likely to accept a student of
      either sex for all parts of the consultation. This information can be used to
      enhance the experience of male and female students and to minimise distress for
      those patients who are less likely to accept the presence of a medical student.

PMID- 16461605
TI  - Biologically confirmed sexually transmitted infection and depressive
      symptomatology among African-American female adolescents.
AB  - OBJECTIVE: To determine prospectively the relation between sexually transmitted
      infection (STI) diagnosis and depressive symptomatology. METHODS: Secondary data
      analyses were performed on 175 sexually active African-American female
      adolescents, who were recruited from high risk neighbourhoods in Birmingham,
      Alabama, United States. RESULTS: ANCOVA was used to compare adolescents who
      tested positive with adolescents who tested negative on three waves of depressive
      symptom scores, controlling for age. The STI positive group had higher depressive
      symptom levels at 6 months relative to the STI negative group. This result was
      moderated by baseline depressive symptom levels: for adolescents above the
      clinical threshold, the STI negative group experienced a decrease in symptoms at
      6 months whereas the STI positive group maintained the same level. For
      adolescents below the clinical threshold, there were no changes in depressive
      symptom levels regardless of diagnosis. CONCLUSIONS: Receiving an STI diagnosis
      may affect depressive symptomatology for those at risk for depression. Screening
      for depression in settings that provide STI testing and treatment may be
      warranted for this population.

PMID- 16461607
TI  - Sexual health problems managed in Australian general practice: a national, cross
      sectional survey.
AB  - OBJECTIVES: To ascertain how frequently Australian general practitioners (GPs)
      identify sexual health (SH) problems, to gain understanding of how SH problems
      are managed in general practice and to determine the characteristics of GPs who
      manage them. METHODS: A secondary analysis of data from the BEACH programme April
      2000-March 2003. BEACH is a cross sectional national survey of GP activity:
      approximately 1000 GPs per year, each records details of 100 consecutive patient
      encounters. Initially, patient reasons for encounter (RFE), suggestive of a SH
      problem, were used to derive a list of SH problems (that is, doctor's
      diagnosis/problem label). Management of these problems was then investigated for
      all encounters with patients aged 12-49 years. The frequency of SH problems,
      their management and the characteristics of GPs managing them, were analysed
      using SAS. RESULTS: During 299,000 encounters with 2990 GPs, 3499 (1.17 per 100
      encounters) STI/SH problems were managed, the majority (81.1%) in females. The
      most common in women were genital candidiasis, vaginal symptoms, urinary
      symptoms, and intermenstrual bleeding, and in men were testicular symptoms,
      genital warts, and urethritis. Tests to exclude specific STIs were seldom taken
      and symptomatic management was common. GPs managing SH problems were younger,
      more likely to be female, have fewer years in practice, work in larger practices;
      hold FRACGP status (all p = <0.001) than those GPs who managed none. CONCLUSION:
      Patients seeking medical attention for SH problems are often managed by GPs.
      Tests to diagnose or exclude specific sexually transmitted infections are seldom
      ordered and symptomatic management is common. Strategies to improve management of
      SH problems in general practice need to be developed and evaluated.

PMID- 16461608
TI  - Estimating STI morbidity in primary care.

PMID- 16461609
TI  - Sexual health in Wales.

PMID- 16461610
TI  - Sexual behaviour and condom use among individuals with a history of symptomatic
      genital herpes.
AB  - OBJECTIVES: This study describes the differences in sexual behaviour in
      individuals with genital herpes (GH) during "symptomatic" and "asymptomatic"
      periods of the disease. METHODS: A cross sectional questionnaire was undertaken
      by 1193 individuals attending clinics between 1998 and 2001. All participants in
      this analysis were in heterosexual, monogamous partnerships, self identified with
      a history of symptomatic GH and with confirmed HSV-2 infection. RESULTS: Sexual
      activity reported during asymptomatic v symptomatic periods of GH was 98% v 40%
      (p<0.001), 76% v 29% (p<0.001), and 25% v 11% (p<0.001) for vaginal, oral, and
      anal intercourse, respectively, while "always" condom use during asymptomatic and
      symptomatic periods was 20% v 35% (p<0.001), 2% v 7% (p<0.001), and 10% v 15% (p
      = 0.131), respectively. The proportion of individuals who either abstained from
      vaginal intercourse or "always" used condoms was 21% v 74% (p<0.001), for
      asymptomatic v symptomatic periods. Multivariable analyses indicated that factors
      associated with engaging in intercourse during symptomatic periods of GH included
      current intrauterine device use (adjusted odds ratio (aOR) = 2.96, 95% confidence
      interval (CI) = 1.46 to 6.02); living in Latin America (aOR = 2.16, CI = 1.19 to
      3.91) or Europe (aOR = 1.67, CI = 1.21 to 2.28), compared with North America;
      previous sexually transmitted disease (aOR = 1.42, CI = 1.08 to 1.89); a higher
      number of sexual acts per month (aOR = 1.09, CI = 1.06 to 1.11); and a higher
      number of GH recurrences per year (aOR = 1.08, CI = 1.03 to 1.12). CONCLUSIONS:
      These data indicate that the majority of people with GH either abstained from
      intercourse or "always" used condoms during symptomatic periods of GH. However,
      condom use was relatively low during asymptomatic periods in comparison with
      symptomatic periods. These results highlight that further education on GH
      prevention is warranted, particularly for symptomatic periods.

PMID- 16461612
TI  - New sexual partners and readiness to seek screening for chlamydia and gonorrhoea:
      predictors among minority young women.
AB  - OBJECTIVES: To determine (1) level of readiness and (2) demographic and
      behavioural predictors of readiness to seek chlamydia (CT) and gonorrhoea (NGC)
      screening in the absence of symptoms after sex with a "new" partner. METHODS:
      Baseline data, obtained as part of a larger randomised controlled clinical trial
      in young women, were analysed. Readiness to seek screening for CT and NGC after
      sex with a "new" partner was assessed using the stages of change framework from
      the transtheoretical model of change-precontemplation, contemplation,
      preparation, and action. Ordinal logistic regression, using the proportional odds
      model, was used to determine predictors of being in action for or having already
      been screened for CT and NGC after sex with a "new" partner. RESULTS: The sample
      consisted of 376 predominantly African American (67%) young women (mean age 18.5
      (SD 1.4) years). The distribution of readiness to seek CT and NGC screening was
      4% precontemplation, 11% contemplation, 28% preparation, and 57% action. The best
      fitting logistic model that predicted being in action for seeking screening after
      sex with a "new" partner included high perceived seriousness of acquiring a
      sexually transmitted infection (OR = 2.02, 95% CI 1.05 to 3.89), and having
      "other" (not steady) partners in the last 6 months (OR = 0.50, 95% C.I. 0.32 to
      0.78) CONCLUSIONS: Many young women report that they were not getting screened
      for CT and NGC after sex with a "new" partner and therefore may be at increased
      risk of an untreated STI. Enhancing level of perceived seriousness of acquiring
      an STI from a "new" partner may increase a young woman's readiness to seek
      screening after initiating a new sexual relationship.

PMID- 16461613
TI  - Refocusing health promotion for syphilis prevention: results of a case-control
      study of men who have sex with men on England's south coast.
AB  - BACKGROUND: Prevention interventions have had little impact on syphilis outbreaks
      among men who have sex with men (MSM) and diagnosis rates continue to rise
      rapidly. Detailed studies of the determinants of syphilis transmission are needed
      to inform new prevention interventions. OBJECTIVE: To investigate factors
      associated with recent syphilis diagnosis and recommend strategies for improved
      prevention interventions. METHODS: A case-control study of MSM attending
      genitourinary medicine (GUM) and HIV outpatient clinics. Cases were MSM testing
      positive for early syphilis, based on either laboratory or microscopy results,
      with those testing negative being controls. All participants completed the same
      anonymous questionnaire covering demographics, lifestyle, sexual behaviour, and
      sexual partnerships. RESULTS: 50 cases and 108 controls returned questionnaires.
      Syphilis diagnosis was significantly associated with sexually transmitted
      infection history, recent recreational drug use, receptive anal sex practices,
      but not insertive ones, higher numbers of oral sex partners, but not specific
      oral sex practices. Overall, there were no differences between HIV positive and
      HIV negative/untested men in reporting of sexual behaviours or partnership
      combinations. The use of public sex settings (backrooms, saunas, "cruising
      grounds," etc) was reported by 68% of all participants and not significantly
      associated with syphilis diagnosis. CONCLUSIONS: Many key behavioural and
      partnership risk factors for syphilis are also risk behaviours for HIV
      transmission and point to the need for integrated strategies that tackle the two
      infections together. Simplified procedures for syphilis screening should be
      available in GUM clinical settings, along with targeted community outreach
      prevention interventions.

PMID- 16461614
TI  - Hepatitis B vaccination for male sex workers: the experience of a specialist GUM
      service.
AB  - BACKGROUND: Male sex workers are at risk of blood borne viruses but may have
      limited access to sexual health services, including vaccination. We explore
      factors associated with hepatitis B vaccination uptake among male sex workers in
      London METHODS: Follow up study of men attending the Working Men's Project, a
      specialist health project for men who sell sex, between 1994 and 2003. RESULTS:
      At baseline 797 men were screened for hepatitis B; 308 were not eligible for
      vaccination because of past or current infection (155, 19.4%) or previous
      vaccination 153 (19.2%). Of the 489 men eligible for a full course of vaccination
      292 (59.8%) completed the course. Completion rates fell over time: men recruited
      up to 1999 were more likely to complete the course than those recruited more
      recently (177/259, 68.3% compared with 115/229, 50.2%, OR 2.14, 95% CI 1.48 to
      3.09). CONCLUSION: This specialist service achieved a high rate of vaccine
      completion in the early years, but the decline is a concern. It may reflect wider
      availability of vaccination elsewhere and a more mobile population of sex
      workers. Shorter courses may achieve a higher completion.

PMID- 16461615
TI  - Men who have sex with men: a comparison of a probability sample survey and a
      community based study.
AB  - We compared characteristics of men who have sex with men (MSM) in a probability
      sample survey with a community based study in London. The majority of men in both
      surveys reported male sex partner(s) in the last year but MSM recruited through
      the population based survey had lower levels of HIV risk behaviour, reported
      fewer sexually transmitted infections and HIV testing than those recruited from
      gay venues. Community samples are likely to overestimate levels of risk behaviour
      among all MSM.

PMID- 16461616
TI  - Basing policy on evidence: low HIV, STIs, and risk behaviour in Dili, East Timor
      argue for more focused interventions.
AB  - BACKGROUND: East Timor is a newly independent, poor nation with many internally
      displaced people and foreign peace keeping forces. Similarities with Cambodia,
      which now has Asia's worst HIV epidemic, caused donors to earmark money for HIV
      prevention in East Timor, but no data were available to plan appropriate
      programmes. OBJECTIVES: To determine levels of infection with HIV and other
      sexually transmitted infections (STIs) and associated risk behaviours in Dili,
      East Timor, in order to guide resource allocation and appropriate prevention and
      care strategies. METHODS: In mid-2003, a cross sectional survey of female sex
      workers, men who have sex with men (MSM), taxi drivers, and soldiers was
      conducted. Participants provided biological specimens and all answered structured
      questionnaires. RESULTS: HIV prevalence was 3% among female sex workers (3/100),
      0.9% among MSM (1/110), and zero in the other groups. All the HIV infected sex
      workers reported sex with foreign clients. Partner turnover reported by all
      groups was among the lowest in Asia, so was condom use. Access to basic HIV
      prevention services, including condoms and STI services, was extremely low in all
      groups. CONCLUSIONS: A few sex workers are infected with HIV in East Timor, but
      the virus is not circulating widely among their clients, and sexual networking is
      limited. The risk of a generalised HIV epidemic in East Timor is minimal. HIV can
      be contained by the provision of basic services to the small minority of the
      population at highest risk, preserving resources for other health and development
      needs.

PMID- 16461617
TI  - Policy at the crossroads: debating the science of badgers and bovine TB.

PMID- 16461621
TI  - Effects of the timing of the administration of Mycoplasma hyopneumoniae bacterin
      on the development of lesions associated with porcine circovirus type 2.
AB  - To determine whether there is an effect of the timing of vaccination on porcine
      circovirus type 2 (PCV-2) replication and PCV-2-associated lesions, 78 pigs were
      randomly assigned to eight groups: group 1 (10 pigs) was vaccinated with a
      commercial Mycoplasma hyopneumoniae vaccine at two and four weeks of age, group 2
      (nine pigs) was vaccinated at four and six weeks of age, group 3 (10 pigs) at six
      and eight weeks of age and group 4 (10 pigs) at eight and 10 weeks of age; group
      5 (nine pigs) was vaccinated once with a double dose at four weeks of age, and
      group 6 (10 pigs) was vaccinated once with a double dose at eight weeks of age.
      Groups 7 and 8, both of 10 pigs, were not vaccinated. At eight weeks of age, the
      pigs in groups 1 to 7 were inoculated with PCV-2. Fourteen days after they had
      been inoculated, the pigs in groups 1, 4 and 5 had significantly (P<0.05) more
      copies of the PCV-2 genome in their serum than the unvaccinated pigs.
      Microscopically, 14 of the 68 inoculated pigs had normal lymphoid tissues, 40 had
      mild PCV-2-associated lymphoid lesions and 14 had moderate lesions. The mean
      overall lymphoid lesions (lymphoid depletion, granulomatous inflammation, and
      quantity of PCV-2 antigen in spleen, tonsil, and five lymph nodes) were
      significantly (P<0.05) more severe in groups 4 and 5 than in groups 2, 3, 7 and
      8.

PMID- 16461622
TI  - Methicillin-resistant Staphylococcus aureus isolated from a veterinary surgeon
      and five dogs in one practice.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from five dogs
      with wound discharges after surgical procedures at a veterinary practice, and
      MRSA with similar molecular and phenotypic characteristics was isolated from the
      nares of one veterinary surgeon in the practice. The pulsed-field gel
      electrophoresis patterns of all the isolates were indistinguishable from each
      other and from the most common human isolates of MRSA in Ireland.

PMID- 16461623
TI  - Clinical application of parenteral nutrition in the treatment of five ponies and
      one donkey with hyperlipaemia.
AB  - Five ponies and one donkey with hyperlipaemia that occurred secondarily to a
      variety of primary clinical conditions were treated with lipid-free partial
      parenteral nutrition comprising equal volumes of 50 per cent glucose and 15 per
      cent amino acids. The infusion supplied energy and protein at rates of 2.6 kJ/kg
      per hour and 34.3 mg/kg per hour, respectively. In all six cases there was a
      prompt and sustained decrease in serum concentrations of triglyceride. In four of
      the six cases a good response to treatment of the primary condition was also seen
      and the subjects were discharged successfully. In the remaining two cases, poor
      clinical response of the primary condition resulted in euthanasia, although
      hyperlipaemia was nevertheless resolved. The main complication of parenteral
      nutrition was hyperglycaemia.

PMID- 16461624
TI  - Evaluation of the Binax NOW Flu A test kit for the rapid detection of equine
      influenza virus.

PMID- 16461625
TI  - Cholelithiasis and chronic cholangiohepatitis in a mute swan (Cygnus olor).

PMID- 16461626
TI  - Granular cell tumour in the spine of a dog.

PMID- 16461627
TI  - Post-traumatic complication due to Wohlfahrtia magnifica larvae on a horse.

PMID- 16461628
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16461629
TI  - Non-therapeutic docking of dogs' tails.

PMID- 16461630
TI  - Day blindness in a German wirehaired pointer.

PMID- 16461631
TI  - RCVS survey of the profession, 2006.

PMID- 16461632
TI  - Treatment of tail gangrene in buffaloes.

PMID- 16461634
TI  - Practice-based clinical research.

PMID- 16461633
TI  - Badger culling and bovine TB.

PMID- 16461636
TI  - "Genome design" model: evidence from conserved intronic sequence in human-mouse
      comparison.
AB  - Introns are shorter in housekeeping genes than in tissue- or development-specific
      genes. Differing explanations have been offered for this phenomenon: selection
      for economy (in housekeeping genes), mutation bias or "genomic design." The large
      scale implementation in this present paper of a rigorous local sequence alignment
      algorithm revealed an unprecedented fraction of evolutionarily conserved DNA in
      human-mouse introns ( approximately 60% of human and approximately 70% of mouse
      intron length remained after masking for lineage-specific repeats). The length
      distributions of both conserved and nonconserved regions are very broad but show
      peaks close to nucleosomal and di-nucleosomal DNA. Both the fraction of conserved
      sequence and its absolute length were higher in introns of tissue-specific genes
      than housekeeping genes. This difference remained after control for between
      species identity of the conserved fraction, mutation rate, and GC content. In a
      more direct control, the product of the conserved sequence fraction and the
      between-species identity of this fraction (which can be considered to be the
      fraction of conserved nucleotides) was greater in introns of tissue-specific
      genes than housekeeping genes. Neither the fraction of intron length covered by
      repeats nor the balance of small insertions and deletions (indels) can explain
      the greater length of introns in tissue-specific genes. The length of the
      conserved intronic DNA in a gene is correlated with the number of functional
      domains in the protein encoded by that gene. These results suggest that the
      greater length of introns in tissue-specific genes is not due to selection for
      economy or mutation bias but instead is related to functional complexity
      (probably mediated by chromatin condensation), and that the evolution of the bulk
      of noncoding DNA is not completely neutral.

PMID- 16461637
TI  - Utilization of a whole genome SNP panel for efficient genetic mapping in the
      mouse.
AB  - Phenotype-driven genetics can be used to create mouse models of human disease and
      birth defects. However, the utility of these mutant models is limited without
      identification of the causal gene. To facilitate genetic mapping, we developed a
      fixed single nucleotide polymorphism (SNP) panel of 394 SNPs as an alternative to
      analyses using simple sequence length polymorphism (SSLP) marker mapping. With
      the SNP panel, chromosomal locations for 22 monogenic mutants were identified.
      The average number of affected progeny genotyped for mapped monogenic mutations
      is nine. Map locations for several mutants have been obtained with as few as four
      affected progeny. The average size of genetic intervals obtained for these
      mutants is 43 Mb, with a range of 17-83 Mb. Thus, our SNP panel allows for
      identification of moderate resolution map position with small numbers of mice in
      a high-throughput manner. Importantly, the panel is suitable for mapping crosses
      from many inbred and wild-derived inbred strain combinations. The chromosomal
      localizations obtained with the SNP panel allow one to quickly distinguish
      between potentially novel loci or remutations in known genes, and facilitates
      fine mapping and positional cloning. By using this approach, we identified DNA
      sequence changes in two ethylnitrosourea-induced mutants.

PMID- 16461638
TI  - Characterization of an Agrobacterium tumefaciens D-psicose 3-epimerase that
      converts D-fructose to D-psicose.
AB  - The noncharacterized gene previously proposed as the D-tagatose 3-epimerase gene
      from Agrobacterium tumefaciens was cloned and expressed in Escherichia coli. The
      expressed enzyme was purified by three-step chromatography with a final specific
      activity of 8.89 U/mg. The molecular mass of the purified protein was estimated
      to be 132 kDa of four identical subunits. Mn2+ significantly increased the
      epimerization rate from D-fructose to D-psicose. The enzyme exhibited maximal
      activity at 50 degrees C and pH 8.0 with Mn2+. The turnover number (k(cat)) and
      catalytic efficiency (k(cat)/Km) of the enzyme for D-psicose were markedly higher
      than those for d-tagatose, suggesting that the enzyme is not D-tagatose 3
      epimerase but D-psicose 3-epimerase. The equilibrium ratio between D-psicose and
      D-fructose was 32:68 at 30 degrees C. D-Psicose was produced at 230 g/liter from
      700-g/liter D-fructose at 50 degrees C after 100 min, corresponding to a
      conversion yield of 32.9%.

PMID- 16461639
TI  - Identification of an endo-beta-1,4-D-xylanase from Magnaporthe grisea by gene
      knockout analysis, purification, and heterologous expression.
AB  - Magnaporthe grisea, a destructive ascomycetous pathogen of rice, secretes cell
      wall-degrading enzymes into a culture medium containing purified rice cell walls
      as the sole carbon source. From M. grisea grown under the culture conditions
      described here, we have identified an expressed sequenced tag, XYL-6, a gene that
      is also expressed in M. grisea-infected rice leaves 24 h postinoculation with
      conidia. This gene encodes a protein about 65% similar to endo-beta-1,4-D
      glycanases within glycoside hydrolase family GH10. A M. grisea knockout mutant
      for XYL-6 was created, and it was shown to be as virulent as the parent strain in
      infecting the rice host. The proteins secreted by the parent strain and by the
      xyl-6Delta mutant were each fractionated by liquid chromatography, and the
      collected fractions were assayed for endo-beta-1,4-D-glucanase or endo-beta-1,4-D
      xylanase activities. Two protein-containing peaks with endo-beta-1,4-D-xylanase
      activity secreted by the parent strain are not detectable in the column eluant of
      the proteins secreted by the mutant. The two endoxylanases (XYL-6alpha and XYL
      6beta) from the parent were each purified to homogeneity. N-terminal amino acid
      sequencing indicated that XYL-6alpha is a fragment of XYL-6beta and that XYL
      6beta is identical to the deduced protein sequence encoded by the XYL-6 gene.
      Finally, XYL-6 was introduced into Pichia pastoris for heterologous expression,
      which resulted in the purification of a fusion protein, XYL-6H, from the Pichia
      pastoris culture filtrate. XYL-6H is active in cleaving arabinoxylan. These
      experiments unequivocally established that the XYL-6 gene encodes a secreted endo
      beta-1,4-D-xylanase.

PMID- 16461640
TI  - Reliable and rapid identification of Listeria monocytogenes and Listeria species
      by artificial neural network-based Fourier transform infrared spectroscopy.
AB  - Differentiation of the species within the genus Listeria is important for the
      food industry but only a few reliable methods are available so far. While a
      number of studies have used Fourier transform infrared (FTIR) spectroscopy to
      identify bacteria, the extraction of complex pattern information from the
      infrared spectra remains difficult. Here, we apply artificial neural network
      technology (ANN), which is an advanced multivariate data-processing method of
      pattern analysis, to identify Listeria infrared spectra at the species level. A
      hierarchical classification system based on ANN analysis for Listeria FTIR
      spectra was created, based on a comprehensive reference spectral database
      including 243 well-defined reference strains of Listeria monocytogenes, L.
      innocua, L. ivanovii, L. seeligeri, and L. welshimeri. In parallel, a univariate
      FTIR identification model was developed. To evaluate the potentials of these
      models, a set of 277 isolates of diverse geographical origins, but not included
      in the reference database, were assembled and used as an independent external
      validation for species discrimination. Univariate FTIR analysis allowed the
      correct identification of 85.2% of all strains and of 93% of the L. monocytogenes
      strains. ANN-based analysis enhanced differentiation success to 96% for all
      Listeria species, including a success rate of 99.2% for correct L. monocytogenes
      identification. The identity of the 277-strain test set was also determined with
      the standard phenotypical API Listeria system. This kit was able to identify 88%
      of the test isolates and 93% of L. monocytogenes strains. These results
      demonstrate the high reliability and strong potential of ANN-based FTIR spectrum
      analysis for identification of the five Listeria species under investigation.
      Starting from a pure culture, this technique allows the cost-efficient and rapid
      identification of Listeria species within 25 h and is suitable for use in a
      routine food microbiological laboratory.

PMID- 16461635
TI  - Decoding the fine-scale structure of a breast cancer genome and transcriptome.
AB  - A comprehensive understanding of cancer is predicated upon knowledge of the
      structure of malignant genomes underlying its many variant forms and the
      molecular mechanisms giving rise to them. It is well established that solid tumor
      genomes accumulate a large number of genome rearrangements during tumorigenesis.
      End Sequence Profiling (ESP) maps and clones genome breakpoints associated with
      all types of genome rearrangements elucidating the structural organization of
      tumor genomes. Here we extend the ESP methodology in several directions using the
      breast cancer cell line MCF-7. First, targeted ESP is applied to multiple
      amplified loci, revealing a complex process of rearrangement and co-amplification
      in these regions reminiscent of breakage/fusion/bridge cycles. Second, genome
      breakpoints identified by ESP are confirmed using a combination of DNA sequencing
      and PCR. Third, in vitro functional studies assign biological function to a
      rearranged tumor BAC clone, demonstrating that it encodes anti-apoptotic
      activity. Finally, ESP is extended to the transcriptome identifying four novel
      fusion transcripts and providing evidence that expression of fusion genes may be
      common in tumors. These results demonstrate the distinct advantages of ESP
      including: (1) the ability to detect all types of rearrangements and copy number
      changes; (2) straightforward integration of ESP data with the annotated genome
      sequence; (3) immortalization of the genome; (4) ability to generate tumor
      specific reagents for in vitro and in vivo functional studies. Given these
      properties, ESP could play an important role in a tumor genome project.

PMID- 16461641
TI  - Bioassay for nisin in milk, processed cheese, salad dressings, canned tomatoes,
      and liquid egg products.
AB  - A sensitive nisin quantification bioassay was constructed, based on Lactococcus
      lactis chromosomally encoding the nisin regulatory proteins NisK and NisR and a
      plasmid with a green fluorescent protein (GFP) variant gfp(uv) gene under the
      control of the nisin-inducible nisA promoter. This strain, LAC275, was capable of
      transducing the signal from extracellular nisin into measurable GFPuv
      fluorescence through the NisRK signal transduction system. The LAC275 cells
      detected nisin concentrations of 10 pg/ml in culture supernatant, 0.2 ng/ml in
      milk, 3.6 ng/g in processed cheese, 1 ng/g in salad dressings and crushed, canned
      tomatoes, and 2 ng/g in liquid egg. This method was up to 1,000 times more
      sensitive than a previously described GFP-based nisin bioassay. This new assay
      made it possible to detect significantly smaller amounts of nisin than the
      presently most sensitive published nisin bioassay based on nisin-induced
      bioluminescence. The major advantage of this sensitivity was that foods could be
      extensively diluted prior to the assay, avoiding potential inhibitory and
      interfering substances present in most food products.

PMID- 16461642
TI  - In vitro kinetic analysis of oligofructose consumption by Bacteroides and
      Bifidobacterium spp. indicates different degradation mechanisms.
AB  - The growth of pure cultures of Bacteroides thetaiotaomicron LMG 11262 and
      Bacteroides fragilis LMG 10263 on fructose and oligofructose was examined and
      compared to that of Bifidobacterium longum BB536 through in vitro laboratory
      fermentations. Gas chromatography (GC) analysis was used to determine the
      different fractions of oligofructose and their degradation during the
      fermentation process. Both B. thetaiotaomicron LMG 11262 and B. fragilis LMG
      10263 were able to grow on oligofructose as fast as on fructose, succinic acid
      being the major metabolite produced by both strains. B. longum BB536 grew slower
      on oligofructose than on fructose. Acetic acid and lactic acid were the main
      metabolites produced when fructose was used as the sole energy source. Increased
      amounts of formic acid and ethanol were produced when oligofructose was used as
      an energy source at the cost of lactic acid. Detailed kinetic analysis revealed a
      preferential metabolism of the short oligofructose fractions (e.g., F2 and F3)
      for B. longum BB536. After depletion of the short fractions, the larger
      oligofructose fractions (e.g., F4, GF4, F5, GF5, and F6) were metabolized, too.
      Both Bacteroides strains did not display such a preferential metabolism and
      degraded all oligofructose fractions simultaneously, transiently increasing the
      fructose concentration in the medium. This suggests a different mechanism for
      oligofructose breakdown between the strain of Bifidobacterium and both strains of
      Bacteroides, which helps to explain the bifidogenic nature of inulin-type
      fructans.

PMID- 16461643
TI  - In vivo emission of dinitrogen by earthworms via denitrifying bacteria in the
      gut.
AB  - Earthworms emit the greenhouse gas nitrous oxide (N2O), and ingested denitrifiers
      in the gut appear to be the main source of this N2O. The primary goal of this
      study was to determine if earthworms also emit dinitrogen (N2), the end product
      of complete denitrification. When [15N]nitrate was injected into the gut, the
      earthworms Aporrectodea caliginosa and Lumbricus terrestris emitted labeled N2
      (and also labeled N2O) under in vivo conditions; emission of N2 by these two
      earthworms was relatively linear and approximated 1.2 and 6.6 nmol N2 per h per g
      (fresh weight), respectively. Isolated gut contents also produced [15N]nitrate
      derived N2 and N2O under anoxic conditions. N2 is formed by N2O reductase, and
      acetylene, an inhibitor of this enzyme, inhibited the emission of [15N]nitrate
      derived N2 by living earthworms. Standard gas chromatographic analysis
      demonstrated that the amount of N2O emitted was relatively linear during initial
      incubation periods and increased in response to acetylene. The calculated rates
      for the native emissions of N2 (i.e., without added nitrate) by A. caliginosa and
      L. terrestris were 1.1 and 1.5 nmol N2 per h per g (fresh weight), respectively;
      these emission rates approximated that of N2O. These collective observations
      indicate that (i) earthworms emit N2 concomitant with the emission of N2O via the
      in situ activity of denitrifying bacteria in the gut and (ii) N2O is
      quantitatively an important denitrification-derived end product under in situ
      conditions.

PMID- 16461644
TI  - Nitrous oxide reductase genes (nosZ) of denitrifying microbial populations in
      soil and the earthworm gut are phylogenetically similar.
AB  - Earthworms emit nitrous oxide (N2O) and dinitrogen (N2). It has been hypothesized
      that the in situ conditions of the earthworm gut activates ingested soil
      denitrifiers during gut passage and leads to these in vivo emissions (M. A. Horn,
      A. Schramm, and H. L. Drake, Appl. Environ. Microbiol. 69:1662-1669, 2003). This
      hypothesis implies that the denitrifiers in the earthworm gut are not endemic to
      the gut but rather are regular members of the soil denitrifier population. To
      test this hypothesis, the denitrifier populations of gut and soil from three
      different sites were comparatively assessed by sequence analysis of nosZ, the
      gene for the terminal enzyme in denitrification, N2O reductase. A total of 182
      and 180 nosZ sequences were retrieved from gut and soil, respectively; coverage
      of gene libraries was 79 to 100%. Many of the nosZ sequences were heretofore
      unknown, clustered with known soil-derived sequences, or were related to N2O
      reductases of the genera Bradyrhizobium, Brucella, Dechloromonas, Flavobacterium,
      Pseudomonas, Ralstonia, and Sinorhizobium. Although the numbers of estimators for
      genotype richness of sequence data from the gut were higher than those of soil,
      only one gut-derived nosZ sequence did not group phylogenetically with any of the
      soil-derived nosZ sequences. Thus, the phylogenies of nosZ from gut and soil were
      not dissimilar, indicating that gut denitrifiers are soil derived.

PMID- 16461646
TI  - Effect of ammonia production by Colletotrichum gloeosporioides on pelB
      activation, pectate lyase secretion, and fruit pathogenicity.
AB  - The accumulation of ammonia and associated tissue alkalinization predispose
      avocado fruit to attack by Colletotrichum gloeosporioides. Secretion of ammonia
      by C. gloeosporioides in the presence of KNO3 was induced by decreasing the pH
      from 7.0 to 4.0. When the fungus was grown at pH 4.0 or 6.0 in the absence of a
      nitrogen source, ammonia did not accumulate, and neither pelB (encoding pectate
      lyase) transcription nor pectate lyase secretion was detected. Under these
      nitrogen starvation conditions, only transcriptional activation of areA, which
      encodes the global nitrogen regulator, was detected. pelB transcription and
      pectate lyase secretion were both detected when C. gloeosporioides was grown at
      pH 6.0 in the presence of ammonia accumulated from different nitrogen sources.
      The early accumulation of ammonia induced early pelB expression and pectate lyase
      secretion. As the external pH increased from 4.0 to 6.0, transcripts of pac1, the
      C. gloeosporioides pacC homolog, also could be detected. Nit mutants of C.
      gloeosporioides, which cannot utilize KNO3 as a nitrogen source, did not secrete
      ammonia, alkalinize the medium, or secrete pectate lyase. If Nit mutants were
      grown at pH 6.0 in the presence of glutamate, then pectate lyase secretion was
      induced. Infiltration of 0.1 M ammonium hydroxide at pH 10 into ripening avocado
      fruits enhanced the activation of quiescent infection and symptom development by
      C. gloeosporioides. These results suggest that ambient pH alkalinization
      resulting from ammonia accumulation and the availability of ammonia as a nitrogen
      source independently regulate pelB expression, pectate lyase secretion, and
      virulence of C. gloeosporioides. These data suggest that alkalinization during C.
      gloeosporioides infection is important for its transformation from the quiescent
      biotrophic stage to the necrotrophic stage of fungal colonization in the fruit
      host.

PMID- 16461645
TI  - Differences in fecal microbiota in different European study populations in
      relation to age, gender, and country: a cross-sectional study.
AB  - A cross-sectional study on intestinal microbiota composition was performed on 230
      healthy subjects at four European locations in France, Germany, Italy, and
      Sweden. The study participants were assigned to two age groups: 20 to 50 years
      (mean age, 35 years; n = 85) and >60 years (mean age, 75 years; n = 145). A set
      of 14 group- and species-specific 16S rRNA-targeted oligonucleotide probes was
      applied to the analysis of fecal samples by fluorescence in situ hybridization
      coupled with flow cytometry. Marked country-age interactions were observed for
      the German and Italian study groups. These interactions were inverse for the
      predominant bacterial groups Eubacterium rectale-Clostridium coccoides and
      Bacteroides-Prevotella. Differences between European populations were observed
      for the Bifidobacterium group only. Proportions of bifidobacteria were two- to
      threefold higher in the Italian study population than in any other study group,
      and this effect was independent of age. Higher proportions of enterobacteria were
      found in all elderly volunteers independent of the location. Gender effects were
      observed for the Bacteroides-Prevotella group, with higher levels in males than
      in females. In summary, age-related differences in the microbiota makeup were
      detected but differed between the study populations from the four countries, each
      showing a characteristic colonization pattern.

PMID- 16461647
TI  - Biodegradation of 3-nitrotyrosine by Burkholderia sp. strain JS165 and Variovorax
      paradoxus JS171.
AB  - The cascade of reactive nitrogen species generated from nitric oxide causes
      modification of proteins, lipids, and nucleic acids in a wide range of organisms.
      3-Nitrotyrosine is one of the most common products of the action of reactive
      nitrogen species on proteins. Although a great deal is known about the formation
      of 3-nitrotyrosine, the subsequent metabolism of this compound is a mystery.
      Variovorax paradoxus JS171 and Burkholderia sp. strain JS165 were isolated from
      soil slurries when 3-nitrotyrosine was provided as the sole carbon, nitrogen, and
      energy source. During growth on 3-nitrotyrosine stoichiometric amounts of nitrite
      were released along with approximately one-half of the theoretically available
      ammonia. The catabolic pathway involving oxidative denitration is distinct from
      the pathway for tyrosine metabolism. The facile isolation and the specific,
      regulated pathway for 3-nitrotyrosine degradation in natural ecosystems suggest
      that there is a significant flux of 3-nitrotyrosine in such environments.

PMID- 16461648
TI  - Molecular cloning and expression of genes encoding a novel dioxygenase involved
      in low- and high-molecular-weight polycyclic aromatic hydrocarbon degradation in
      Mycobacterium vanbaalenii PYR-1.
AB  - Mycobacterium vanbaalenii PYR-1 is able to metabolize a wide range of low- and
      high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs). A 20-kDa
      protein was upregulated in PAH-metabolizing M. vanbaalenii PYR-1 cells compared
      to control cultures. The differentially expressed protein was identified as a
      beta subunit of the terminal dioxygenase using mass spectrometry. PCR with
      degenerate primers designed based on de novo sequenced peptides and a series of
      plaque hybridizations were done to screen the M. vanbaalenii PYR-1 genomic
      library. The genes, designated nidA3B3, encoding the alpha and beta subunits of
      terminal dioxygenase, were subsequently cloned and sequenced. The deduced enzyme
      revealed close similarities to the corresponding PAH ring-hydroxylating
      dioxygenases from Mycobacterium and Rhodococcus spp. but had the highest
      similarity, 61.9%, to the alpha subunit from Nocardioides sp. strain KP7. The
      alpha subunit also showed 52% sequence homology with the previously reported NidA
      from M. vanbaalenii PYR-1. The genes nidA3B3 were subcloned into the expression
      vector pET-17b, and the enzyme activity in Escherichia coli cells was
      reconstituted through coexpression with the ferredoxin (PhdC) and ferredoxin
      reductase (PhdD) genes of the phenanthrene dioxygenase from Nocardioides sp.
      strain KP7. The recombinant PAH dioxygenase appeared to favor the HMW PAH
      substrates fluoranthene, pyrene, and phenanthrene. Several other PAHs, including
      naphthalene, anthracene, and benz[a]anthracene, were also converted to their
      corresponding cis-dihydrodiols. The recombinant E. coli, however, did not show
      any dioxygenation activity for phthalate and biphenyl. The upregulation of
      nidA3B3 in M. vanbaalenii PYR-1 induced by PAHs was confirmed by reverse
      transcription-PCR analysis.

PMID- 16461649
TI  - Identification of genes associated with survival of Salmonella enterica serovar
      Enteritidis in chicken egg albumen.
AB  - Salmonella enterica consists of over 2,000 serovars that are major causes of
      morbidity and mortality associated with contaminated food. Despite similarities
      among serovars of Salmonella enterica, many demonstrate unique host
      specificities, epidemiological characteristics, and clinical manifestations. One
      of the unique epidemiological characteristics of the serovar Enteritidis is that
      it is the only bacterium routinely transmitted to humans through intact chicken
      eggs. Therefore, Salmonella enterica serovar Enteritidis must be able to persist
      inside chicken eggs to be transmitted to humans, and its survival in egg is
      important for its transmission to the human population. The ability of Salmonella
      enterica serovar Enteritidis to survive in and transmit through eggs may have
      contributed to its drastically increased prevalence in the 1980s and 1990s. In
      the present study, using transposon-mediated mutagenesis, we have identified
      genes important for the association of Salmonella enterica serovar Enteritidis
      with chicken eggs. Our results indicate that genes involved in cell wall
      structural and functional integrity, and nucleic acid and amino acid metabolism
      are important for Salmonella enterica serovar Enteritidis to persist in egg
      albumen. Two regions unique to Salmonella enterica serovar Enteritidis were also
      identified, one of which enhanced the survival of a Salmonella enterica serovar
      Typhimurium isolate in egg albumen. The implication of our results to the serovar
      specificity of Salmonella enterica is also explored in the present study.

PMID- 16461650
TI  - Purification, characterization, and gene cloning of a novel maltosyltransferase
      from an Arthrobacter globiformis strain that produces an alternating alpha-1,4-
      and alpha-1,6-cyclic tetrasaccharide from starch.
AB  - A glycosyltransferase, involved in the synthesis of cyclic maltosylmaltose [CMM;
      cyclo-{-->6)-alpha-D-Glcp(1-->4)-alpha-D-Glcp(1-->6)-alpha-D-Glcp(1-->4)-alpha-D
      Glcp(1-->}] from starch, was purified to homogeneity from the culture supernatant
      of Arthrobacter globiformis M6. The CMM-forming enzyme had a molecular mass of
      71.7 kDa and a pI of 3.6. The enzyme was most active at pH 6.0 and 50 degrees C
      and was stable from pH 5.0 to 9.0 and up to 30 degrees C. The addition of 1 mM
      Ca2+ enhanced the thermal stability of the enzyme up to 45 degrees C. The enzyme
      acted on maltooligosaccharides that have degrees of polymerization of > or =3,
      amylose, and soluble starch to produce CMM but failed to act on
      cyclomaltodextrins, pullulan, and dextran. The mechanism for the synthesis of CMM
      from maltotetraose was determined as follows: (i) maltotetraose + maltotetraose -
      > 6(4)-O-alpha-maltosyl-maltotetraose + maltose and (ii) 6(4)-O-alpha-maltosyl
      maltotetraose --> CMM + maltose. Thus, the CMM-forming enzyme was found to be a
      novel maltosyltransferase (6MT) catalyzing both intermolecular and intramolecular
      alpha-1,6-maltosyl transfer reactions. The gene for 6MT, designated cmmA, was
      isolated from a genomic library of A. globiformis M6. The cmmA gene consisted of
      1,872 bp encoding a signal peptide of 40 amino acids and a mature protein of 583
      amino acids with a calculated molecular mass of 64,637. The deduced amino acid
      sequence showed similarities to alpha-amylase and cyclomaltodextrin
      glucanotransferase. The four conserved regions common in the alpha-amylase family
      enzymes were also found in 6MT, indicating that 6MT should be assigned to this
      family.

PMID- 16461651
TI  - Specific detection of Xanthomonas axonopodis pv. dieffenbachiae in anthurium
      (Anthurium andreanum) tissues by nested PCR.
AB  - Efficient control of Xanthomonas axonopodis pv. dieffenbachiae, the causal agent
      of anthurium bacterial blight, requires a sensitive and reliable diagnostic tool.
      A nested PCR test was developed from a sequence-characterized amplified region
      marker identified by randomly amplified polymorphic DNA PCR for the detection of
      X. axonopodis pv. dieffenbachiae. Serological and pathogenicity tests were
      performed concurrently with the nested PCR test with a large collection of X.
      axonopodis pv. dieffenbachiae strains that were isolated worldwide and are
      pathogenic to anthurium and/or other aroids. The internal primer pair directed
      amplification of the expected product (785 bp) for all 70 X. axonopodis pv.
      dieffenbachiae strains pathogenic to anthurium tested and for isolates
      originating from syngonium and not pathogenic to anthurium. This finding is
      consistent with previous studies which indicated that there is a high level of
      relatedness between strains from anthurium and strains from syngonium. Strains
      originating from the two host genera can be distinguished by restriction analysis
      of the amplification product. No amplification product was obtained with 98
      strains of unrelated phytopathogenic bacteria or saprophytic bacteria from the
      anthurium phyllosphere, except for a weak signal obtained for one X. axonopodis
      pv. allii strain. Nevertheless, restriction enzyme analysis permitted the two
      pathovars to be distinguished. The detection threshold obtained with pure
      cultures or plant extracts (10(3) CFU ml(-1)) allowed detection of the pathogen
      from symptomless contaminated plants. This test could be a useful diagnostic tool
      for screening propagation stock plant material and for monitoring international
      movement of X. axonopodis pv. dieffenbachiae.

PMID- 16461652
TI  - Pure-culture growth of fermentative bacteria, facilitated by H2 removal:
      bioenergetics and H2 production.
AB  - We used an H2-purging culture vessel to replace an H2-consuming syntrophic
      partner, allowing the growth of pure cultures of Syntrophothermus lipocalidus on
      butyrate and Aminobacterium colombiense on alanine. By decoupling the syntrophic
      association, it was possible to manipulate and monitor the single organism's
      growth environment and determine the change in Gibbs free energy yield (DeltaG)
      in response to changes in the concentrations of reactants and products, the
      purging rate, and the temperature. In each of these situations, H2 production
      changed such that DeltaG remained nearly constant for each organism (-11.1 +/-
      1.4 kJ mol butyrate(-1) for S. lipocalidus and -58.2 +/- 1.0 kJ mol alanine(-1)
      for A. colombiense). The cellular maintenance energy, determined from the DeltaG
      value and the hydrogen production rate at the point where the cell number was
      constant, was 4.6 x 10(-13) kJ cell(-1) day(-1) for S. lipocalidus at 55 degrees
      C and 6.2 x 10(-13) kJ cell(-1) day(-1) for A. colombiense at 37 degrees C. S.
      lipocalidus, in particular, seems adapted to thrive under conditions of low
      energy availability.

PMID- 16461653
TI  - The naphthalene catabolic (nag) genes of Polaromonas naphthalenivorans CJ2:
      evolutionary implications for two gene clusters and novel regulatory control.
AB  - Polaromonas naphthalenivorans CJ2, found to be responsible for the degradation of
      naphthalene in situ at a coal tar waste-contaminated site (C.-O. Jeon et al.,
      Proc. Natl. Acad. Sci. USA 100:13591-13596, 2003), is able to grow on mineral
      salts agar media with naphthalene as the sole carbon source. Beginning from a 484
      bp nagAc-like region, we used a genome walking strategy to sequence genes
      encoding the entire naphthalene degradation pathway andadditional flanking
      regions. We found that the naphthalene catabolic genes in P. naphthalenivorans
      CJ2 were divided into one large and one small gene cluster, separated by an
      unknown distance. The large gene cluster (nagRAaGHAbAcAdBFCQEDJI'ORF1tnpA) is
      bounded by a LysR-type regulator (nagR). The small cluster (nagR2ORF2I"KL) is
      bounded by a MarR-type regulator (nagR2). The catabolic genes of P.
      naphthalenivorans CJ2 were homologous to many of those of Ralstonia U2, which
      uses the gentisate pathway to convert naphthalene to central metabolites.
      However, three open reading frames (nagY, nagM, and nagN), present in Ralstonia
      U2, were absent. Also, P. naphthalenivorans carries two copies of gentisate
      dioxygenase (nagI) with 77.4% DNA sequence identity to one another and 82% amino
      acid identity to their homologue in Ralstonia sp. strain U2. Investigation of the
      operons using reverse transcription PCR showed that each cluster was controlled
      independently by its respective promoter. Insertional inactivation and lacZ
      reporter assays showed that nagR2 is a negative regulator and that expression of
      the small cluster is not induced by naphthalene, salicylate, or gentisate.
      Association of two putative Azoarcus-related transposases with the large cluster
      and one Azoarcus-related putative salicylate 5-hydroxylase gene (ORF2) in the
      small cluster suggests that mobile genetic elements were likely involved in
      creating the novel arrangement of catabolic and regulatory genes in P.
      naphthalenivorans.

PMID- 16461654
TI  - The aflatoxin biosynthesis cluster gene, aflX, encodes an oxidoreductase involved
      in conversion of versicolorin A to demethylsterigmatocystin.
AB  - Biosynthesis of the toxic and carcinogenic aflatoxins by the fungus Aspergillus
      flavus is a complicated process involving more that 27 enzymes and regulatory
      factors encoded by a clustered group of genes. Previous studies found that three
      enzymes, encoded by verA, ver-1, and aflY, are required for conversion of
      versicolorin A (VA), to demethylsterigmatocystin. We now show that a fourth
      enzyme, encoded by the previously uncharacterized gene, aflX (ordB), is also
      required for this conversion. A homolog of this gene, stcQ, is present in the A.
      nidulans sterigmatocystin (ST) biosynthesis cluster. Disruption of aflX in
      Aspergillus flavus gave transformants that accumulated approximately 4-fold more
      VA and fourfold less aflatoxin than the untransformed strain. Southern and
      Northern blot analyses confirmed that aflX was the only gene disrupted in these
      transformants. Feeding ST or O-methylsterigmatocystin, but not VA or earlier
      precursor metabolites, restored normal levels of AF production. The protein
      encoded by aflX is predicted to have domains typical of an NADH-dependent
      oxidoreductase. It has 27% amino acid identity to a protein encoded by the
      aflatoxin cluster gene, aflO (avfA). Some of domains in the protein are similar
      to those of epoxide hydrolases.

PMID- 16461655
TI  - Novel genetic variants of Anaplasma phagocytophilum, Anaplasma bovis, Anaplasma
      centrale, and a novel Ehrlichia sp. in wild deer and ticks on two major islands
      in Japan.
AB  - Wild deer are one of the important natural reservoir hosts of several species of
      Ehrlichia and Anaplasma that cause human ehrlichiosis or anaplasmosis in the
      United States and Europe. The primary aim of the present study was to determine
      whether and what species of Ehrlichia and Anaplasma naturally infect deer in
      Japan. Blood samples obtained from wild deer on two major Japanese islands,
      Hokkaido and Honshu, were tested for the presence of Ehrlichia and Anaplasma by
      PCR assays and sequencing of the 16S rRNA genes, major outer membrane protein p44
      genes, and groESL. DNA representing four species and two genera of Ehrlichia and
      Anaplasma was identified in 33 of 126 wild deer (26%). DNA sequence analysis
      revealed novel strains of Anaplasma phagocytophilum, a novel Ehrlichia sp.,
      Anaplasma centrale, and Anaplasma bovis in the blood samples from deer. None of
      these have been found previously in deer. The new Ehrlichia sp., A. bovis, and A.
      centrale were also detected in Hemaphysalis longicornis ticks from Honshu Island.
      These results suggest that enzootic cycles of Ehrlichia and Anaplasma species
      distinct from those found in the United States or Europe have been established in
      wild deer and ticks in Japan.

PMID- 16461656
TI  - Isolation and expression of the lysis genes of Actinomyces naeslundii phage Av-1.
AB  - Like most gram-positive oral bacteria, Actinomyces naeslundii is resistant to
      salivary lysozyme and to most other lytic enzymes. We are interested in studying
      the lysins of phages of this important oral bacterium as potential diagnostic and
      therapeutic agents. To identify the Actinomyces phage genes encoding these
      species-specific enzymes in Escherichia coli, we constructed a new cloning
      vector, pAD330, that can be used to enrich for and isolate phage holin genes,
      which are located adjacent to the lysin genes in most phage genomes. Cloned holin
      insert sequences were used to design sequencing primers to identify nearby lysin
      genes by using whole phage DNA as the template. From partial digestions of A.
      naeslundii phage Av-1 genomic DNA we were able to clone, in independent
      experiments, inserts that complemented the defective lambda holin in pAD330, as
      evidenced by extensive lysis after thermal induction. The DNA sequence of the
      inserts in these plasmids revealed that both contained the complete lysis region
      of Av-1, which is comprised of two holin-like genes, designated holA and holB,
      and an endolysin gene, designated lysA. We were able to subclone and express
      these genes and determine some of the functional properties of their gene
      products.

PMID- 16461657
TI  - Only a few fungal species dominate highly diverse mycofloras associated with the
      common reed.
AB  - Plants are naturally colonized by many fungal species that produce effects
      ranging from beneficial to pathogenic. However, how many of these fungi are
      linked with a single host plant has not been determined. Furthermore, the
      composition of plant-associated fungal communities has not been rigorously
      determined. We investigated these essential issues by employing the perennial
      wetland reed Phragmites australis as a model. DNA extracted from roots, rhizomes,
      stems, and leaves was used for amplification and cloning of internal transcribed
      spacer rRNA gene fragments originating from reed-associated fungi. A total of
      1,991 clones from 15 clone libraries were differentiated by restriction fragment
      length polymorphism analyses into 345 operational taxonomical units (OTUs).
      Nonparametric estimators for total richness (Chao1 and ACE) and also a parametric
      log normal model predicted a total of about 750 OTUs if the libraries were
      infinite. Sixty-two percent of the OTUs sequenced were novel at a threshold of
      3%. Several of these OTUs represented undocumented fungal species, which also
      included higher taxonomic levels. In spite of the high diversity of the OTUs, the
      mycofloras of vegetative organs were dominated by just a few typical fungi, which
      suggested that competition and niche differentiation influence the composition of
      plant-associated fungal communities. This suggestion was independently supported
      by the results of nested PCR assays specifically monitoring two OTUs over 3
      years, which revealed significant preferences for host habitat and host organ.

PMID- 16461658
TI  - Engineering plant-microbe symbiosis for rhizoremediation of heavy metals.
AB  - The use of plants for rehabilitation of heavy-metal-contaminated environments is
      an emerging area of interest because it provides an ecologically sound and safe
      method for restoration and remediation. Although a number of plant species are
      capable of hyperaccumulation of heavy metals, the technology is not applicable
      for remediating sites with multiple contaminants. A clever solution is to combine
      the advantages of microbe-plant symbiosis within the plant rhizosphere into an
      effective cleanup technology. We demonstrated that expression of a metal-binding
      peptide (EC20) in a rhizobacterium, Pseudomonas putida 06909, not only improved
      cadmium binding but also alleviated the cellular toxicity of cadmium. More
      importantly, inoculation of sunflower roots with the engineered rhizobacterium
      resulted in a marked decrease in cadmium phytotoxicity and a 40% increase in
      cadmium accumulation in the plant root. Owing to the significantly improved
      growth characteristics of both the rhizobacterium and plant, the use of EC20
      expressing P. putida endowed with organic-degrading capabilities may be a
      promising strategy to remediate mixed organic-metal-contaminated sites.

PMID- 16461659
TI  - Biocontrol of the food-borne pathogens Listeria monocytogenes and Salmonella
      enterica serovar Poona on fresh-cut apples with naturally occurring bacterial and
      yeast antagonists.
AB  - Fresh-cut apples contaminated with either Listeria monocytogenes or Salmonella
      enterica serovar Poona, using strains implicated in outbreaks, were treated with
      one of 17 antagonists originally selected for their ability to inhibit fungal
      postharvest decay on fruit. While most of the antagonists increased the growth of
      the food-borne pathogens, four of them, including Gluconobacter asaii (T1-D1), a
      Candida sp. (T4-E4), Discosphaerina fagi (ST1-C9), and Metschnikowia pulcherrima
      (T1-E2), proved effective in preventing the growth or survival of food-borne
      human pathogens on fresh-cut apple tissue. The contaminated apple tissue plugs
      were stored for up to 7 days at two different temperatures. The four antagonists
      survived or grew on the apple tissue at 10 or 25 degrees C. These four
      antagonists reduced the Listeria monocytogenes populations and except for the
      Candida sp. (T4-E4), also reduced the S. enterica serovar Poona populations. The
      reduction was higher at 25 degrees C than at 10 degrees C, and the growth of the
      antagonists, as well as pathogens, increased at the higher temperature.

PMID- 16461660
TI  - Determination of essential and variable residues in pediocin PA-1 by NNK
      scanning.
AB  - Pediocin PA-1 is an antimicrobial peptide (called bacteriocin) that shows
      inhibitory activity against the food-borne pathogen Listeria monocytogenes. To
      elucidate which residue(s) is responsible for this function, the antimicrobial
      activities of pediocin PA-1 mutants were evaluated and compared. Each of the 44
      native codons was replaced with the NNK triplet oligonucleotide in a technique
      termed NNK scanning, and 35 mutations at each position were examined for
      antimicrobial activities using a modified colony overlay screening method. As a
      consequence, the functional responsibility of each residue was estimated by
      counting the number of active mutants, allowing us to identify candidate
      essential/variable residues. Activity was abrogated by many of the mutations at
      residues Y2, G6, C9, C14, C24, W33, G37, and C44, indicating that these residues
      may be essential. In contrast, activity was retained by almost all versions
      harboring mutations at K1, T8, G10, S13, G19, N28, and N41, indicating that these
      are functionally redundant residues. Sequence analysis revealed that only the
      wild type was active and 14 and 11 substitutions were inactive at G6 and C14,
      respectively, while 12 and 11 substitutions were active and 2 and 0 substitutions
      were inactive at T8 and K1, respectively. These findings suggest that NNK
      scanning is effective for determining essential and variable residues in pediocin
      PA-1, leading to an elucidation of structure-function relationships and to
      improvements in the antimicrobial function efficiently by peptide engineering.

PMID- 16461661
TI  - Molecular and genetic characterization of a novel nisin variant produced by
      Streptococcus uberis.
AB  - Streptococcus uberis is one of the principal causative agents of bovine mastitis.
      In this study, we report that S. uberis strain 42 produces a lantibiotic, nisin
      U, which is 78% identical (82% similar) to nisin A from Lactococcus lactis. The
      15.6-kb nisin U locus comprises 11 open reading frames, similar in putative
      functionality but differing in arrangement from that of the nisin A biosynthetic
      cluster. The nisin U producer strain exhibits specific resistance (immunity) to
      nisin U and cross-resistance to nisin A, a finding consistent with the 55%
      sequence similarity of their respective immunity peptides. Homologues of the
      nisin U structural gene were identified in several additional S. uberis strains,
      and in each case cross-protective immunity was expressed to nisin A and to the
      other producers of nisin U and its variants. To our knowledge, this is the first
      report both of characterization of a bacteriocin by S. uberis, as well as of a
      member of the nisin family of peptides in a species other than L. lactis.

PMID- 16461662
TI  - Carbon isotope fractionation during anaerobic degradation of methyl tert-butyl
      ether under sulfate-reducing and methanogenic conditions.
AB  - Methyl tert-butyl ether (MTBE), an octane enhancer and a fuel oxygenate in
      reformulated gasoline, has received increasing public attention after it was
      detected as a major contaminant of water resources. Although several techniques
      have been developed to remediate MTBE-contaminated sites, the fate of MTBE is
      mainly dependent upon natural degradation processes. Compound-specific stable
      isotope analysis has been proposed as a tool to distinguish the loss of MTBE due
      to biodegradation from other physical processes. Although MTBE is highly
      recalcitrant, anaerobic degradation has been demonstrated under different anoxic
      conditions and may be an important process. To accurately assess in situ MTBE
      degradation through carbon isotope analysis, carbon isotope fractionation during
      MTBE degradation by different cultures under different electron-accepting
      conditions needs to be investigated. In this study, carbon isotope fractionation
      during MTBE degradation under sulfate-reducing and methanogenic conditions was
      studied in anaerobic cultures enriched from two different sediments. Significant
      enrichment of 13C in residual MTBE during anaerobic biotransformation was
      observed under both sulfate-reducing and methanogenic conditions. The isotopic
      enrichment factors (epsilon) estimated for each enrichment were almost identical
      (-13.4 per thousand to -14.6 per thousand; r2 = 0.89 to 0.99). A epsilon value of
      -14.4 per thousand+/- 0.7 per thousand was obtained from regression analysis (r2
      = 0.97, n = 55, 95% confidence interval), when all data from our MTBE
      transforming anaerobic cultures were combined. The similar magnitude of carbon
      isotope fractionation in all enrichments regardless of culture or electron
      accepting condition suggests that the terminal electron-accepting process may not
      significantly affect carbon isotope fractionation during anaerobic MTBE
      degradation.

PMID- 16461663
TI  - Nonlinear dependency of intracellular fluxes on growth rate in miniaturized
      continuous cultures of Escherichia coli.
AB  - A novel mini-scale chemostat system was developed for the physiological
      characterization of 10-ml cultures. The parallel operation of eight such mini
      scale chemostats was exploited for systematic 13C analysis of intracellular
      fluxes over a broad range of growth rates in glucose-limited Escherichia coli. As
      expected, physiological variables changed monotonously with the dilution rate,
      allowing for the assessment of maintenance metabolism. Despite the linear
      dependence of total cellular carbon influx on dilution rate, the distribution of
      almost all major fluxes varied nonlinearly with dilution rate. Most prominent
      were the distinct maximum of glyoxylate shunt activity and the concomitant
      minimum of tricarboxylic acid cycle activity at low to intermediate dilution
      rates of 0.05 to 0.2 h(-1). During growth on glucose, this glyoxylate shunt
      activity is best understood from a network perspective as the recently described
      phosphoenolpyruvate (PEP)-glyoxylate cycle that oxidizes PEP (or pyruvate) to
      CO2. At higher or extremely low dilution rates, in vivo PEP-glyoxylate cycle
      activity was low or absent. The step increase in pentose phosphate pathway
      activity at around 0.2 h(-1) was not related to the cellular demand for the
      reduction equivalent NADPH, since NADPH formation was 20 to 50% in excess of the
      anabolic demand at all dilution rates. The results demonstrate that mini-scale
      continuous cultivation enables quantitative and parallel characterization of
      intra- and extracellular phenotypes in steady state, thereby greatly reducing
      workload and costs for stable-isotope experiments.

PMID- 16461664
TI  - Differential expression of proteins and genes in the lag phase of Lactococcus
      lactis subsp. lactis grown in synthetic medium and reconstituted skim milk.
AB  - We investigated protein and gene expression in the lag phase of Lactococcus
      lactis subsp. lactis CNRZ 157 and compared it to the exponential and stationary
      phases. By means of two-dimensional polyacrylamide gel electrophoresis, 28 highly
      expressed lag-phase proteins, implicated in nucleotide metabolism, glycolysis,
      stress response, translation, transcription, cell division, amino acid
      metabolism, and coenzyme synthesis, were identified. Among the identified
      proteins, >2-fold induction and down-regulation in the lag phase were determined
      for 12 proteins in respect to the exponential phase and for 18 proteins in
      respect to the stationary phase. Transcriptional changes of the lag-phase
      proteins in L. lactis were studied by oligonucleotide microarrays. Good
      correlation between protein and gene expression studies was demonstrated for
      several differentially expressed proteins, including nucleotide biosynthetic
      enzymes, adenylosuccinate synthase (PurA), IMP dehydrogenase (GuaB), and
      aspartate carbamoyl transferase (PyrB); heat-shock protein DnaK; serine
      hydroxymethyl transferase (GlyA); carbon catabolite control protein (CcpA);
      elongation factor G (FusA); and cell division protein (FtsZ).

PMID- 16461665
TI  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry for
      the discrimination of food-borne microorganisms.
AB  - A methodology based on matrix-assisted laser desorption ionization-time of flight
      mass spectrometry of intact bacterial cells was used for rapid discrimination of
      24 bacterial species, and detailed analyses to identify Escherichia coli O157:H7
      were carried out. Highly specific mass spectrometric profiles of pathogenic and
      nonpathogenic bacteria that are well-known major food contaminants were obtained,
      uploaded in a specific database, and made available on the Web. In order to
      standardize the analytical protocol, several experimental, sample preparation,
      and mass spectrometry parameters that can affect the reproducibility and accuracy
      of data were evaluated. Our results confirm the conclusion that this strategy is
      a powerful tool for rapid and accurate identification of bacterial species and
      that mass spectrometric methodologies could play an essential role in polyphasic
      approaches to the identification of pathogenic bacteria.

PMID- 16461666
TI  - Identification of QuiP, the product of gene PA1032, as the second acyl-homoserine
      lactone acylase of Pseudomonas aeruginosa PAO1.
AB  - The relevance of the acyl homoserine lactone (acyl-HSL) quorum signals N-3
      oxododecanoyl-homoserine lactone (3OC12HSL) and N-butanoyl-homoserine lactone to
      the biology and virulence of Pseudomonas aeruginosa is well investigated.
      Previously, P. aeruginosa was shown to degrade long-chain, but not short-chain,
      acyl-HSLs as sole carbon and energy sources (J. J. Huang, J.-I. Han, L.-H. Zhang,
      and J. R. Leadbetter, Appl. Environ. Microbiol. 69:5941-5949, 2003). A gene
      encoding an enzyme with acyl-HSL acylase activity, pvdQ (PA2385), was identified,
      but it was not required for acyl-HSL utilization. This indicated that P.
      aeruginosa encodes another acyl-HSL acylase, which we identify here. A comparison
      of total cell proteins of cultures grown with long-acyl acyl-HSLs versus other
      substrates implicated the involvement of a homolog of PvdQ, the product of gene
      PA1032, for which we propose the name QuiP. Transposon mutants of quiP were
      defective for growth when P. aeruginosa was cultured in medium containing
      decanoyl-HSL as a sole carbon and energy source. Complementation with a
      functional copy of quiP rescued this growth defect. When P. aeruginosa was grown
      in buffered lysogeny broth, constitutive expression of QuiP in P. aeruginosa led
      to decreased accumulations of the quorum signal 3OC12HSL, relative to the wild
      type. Heterologous expression of QuiP was sufficient to confer long-chain acyl
      HSL acylase activity upon Escherichia coli. Examination of gene expression
      patterns during acyl-HSL-dependent growth of P. aeruginosa further supported the
      involvement of quiP in signal decay and revealed other genes also possibly
      involved. It is not yet known under which "natural" conditions quiP is expressed
      or how P. aeruginosa balances the expression of its quorum-sensing systems with
      the expression of its acyl-HSL acylase activities.

PMID- 16461667
TI  - Coexistence of Burkholderia, Cupriavidus, and Rhizobium sp. nodule bacteria on
      two Mimosa spp. in Costa Rica.
AB  - rRNA gene sequencing and PCR assays indicated that 215 isolates of root nodule
      bacteria from two Mimosa species at three sites in Costa Rica belonged to the
      genera Burkholderia, Cupriavidus, and Rhizobium. This is the first report of
      Cupriavidus sp. nodule symbionts for Mimosa populations within their native
      geographic range in the neotropics. Burkholderia spp. predominated among samples
      from Mimosa pigra (86% of isolates), while there was a more even distribution of
      Cupriavidus, Burkholderia, and Rhizobium spp. on Mimosa pudica (38, 37, and 25%
      of isolates, respectively). All Cupriavidus and Burkholderia genotypes tested
      formed root nodules and fixed nitrogen on both M. pigra and M. pudica, and
      sequencing of rRNA genes in strains reisolated from nodules verified identity
      with inoculant strains. Inoculation tests further indicated that both Cupriavidus
      and Burkholderia spp. resulted in significantly higher plant growth and nodule
      nitrogenase activity (as measured by acetylene reduction assays) relative to
      plant performance with strains of Rhizobium. Given the prevalence of Burkholderia
      and Cupriavidus spp. on these Mimosa legumes and the widespread distribution of
      these plants both within and outside the neotropics, it is likely that both beta
      proteobacterial genera are more ubiquitous as root nodule symbionts than
      previously believed.

PMID- 16461669
TI  - Characterization of the tre locus and analysis of trehalose cryoprotection in
      Lactobacillus acidophilus NCFM.
AB  - Freezing and lyophilization are common methods used for preservation and storage
      of microorganisms during the production of concentrated starter cultures destined
      for industrial fermentations or product formulations. The compatible solute
      trehalose has been widely reported to protect bacterial, yeast and animal cells
      against a variety of environmental stresses, particularly freezing and
      dehydration. Analysis of the Lactobacillus acidophilus NCFM genome revealed a
      putative trehalose utilization locus consisting of a transcriptional regulator,
      treR; a trehalose phosphoenolpyruvate transferase system (PTS) transporter, treB;
      and a trehalose-6-phosphate hydrolase, treC. The objective of this study was to
      characterize the tre locus in L. acidophilus and determine whether or not
      intracellular uptake of trehalose contributes to cryoprotection. Cells subjected
      to repeated freezing and thawing cycles were monitored for survival in the
      presence of various concentrations of trehalose. At 20% trehalose a 2-log
      increase in survival was observed. The trehalose PTS transporter and trehalose
      hydrolase were disrupted by targeted plasmid insertions. The resulting mutants
      were unable to grow on trehalose, indicating that both trehalose transport into
      the cell via a PTS and hydrolysis via a trehalose-6-phosphate hydrolase were
      necessary for trehalose fermentation. Trehalose uptake was found to be
      significantly reduced in the transporter mutant but unaffected in the hydrolase
      mutant. Additionally, the cryoprotective effect of trehalose was reduced in these
      mutants, suggesting that intracellular transport and hydrolysis contribute
      significantly to cryoprotection.

PMID- 16461668
TI  - Genetic variance in the composition of two functional groups (diazotrophs and
      cyanobacteria) from a hypersaline microbial mat.
AB  - Examination of variation in ecological communities can lead to an understanding
      of the forces that structure communities, the consequences of change at the
      ecosystem level, and the relevant scales involved. This study details spatial and
      seasonal variability in the composition of nitrogen-fixing and cyanobacterial
      (i.e., oxygenic photosynthetic) functional groups of a benthic, hypersaline
      microbial mat from Salt Pond, San Salvador Island, Bahamas. This system shows
      extreme annual variability in the salinity of the overlying water and the extent
      of water coverage. Analysis of molecular variance and F(ST) tests of genetic
      differentiation of nifH and cyanobacterial 16S rRNA gene clone libraries allowed
      for changes at multiple taxonomic levels (i.e., above, below, and at the species
      level) to inform the conclusions regarding these functional groups. Composition
      of the nitrogen-fixing community showed significant seasonal changes related to
      salinity, while cyanobacterial composition showed no consistent seasonal pattern.
      Both functional groups exhibited significant spatial variation, changing with
      depth in the mat and horizontally with distance from the shoreline. The patterns
      of change suggest that cyanobacterial composition was more insensitive to water
      stress, and consequently, cyanobacteria dominated the nitrogen-fixing community
      during dry months but gave way to a more diverse community of diazotrophs in wet
      months. This seasonal pattern may allow the mat community to respond quickly to
      water-freshening events after prolonged dry conditions (system recovery) and
      maintain ecosystem function in the face of disturbance during the wet season
      (system resilience).

PMID- 16461670
TI  - Sequence variation among group III F-specific RNA coliphages from water samples
      and swine lagoons.
AB  - Typing of F-specific RNA (FRNA) coliphages has been proposed as a useful method
      for distinguishing human from animal fecal contamination in environmental
      samples. Group II and III FRNA coliphages are generally associated with human
      wastes, but several exceptions have been noted. In the present study, we have
      genotyped and partially sequenced group III FRNA coliphage field isolates from
      swine lagoons in North Carolina (NC) and South Carolina (SC), along with isolates
      from surface waters and municipal wastewaters. Phylogenetic analysis of a region
      of the 5' end of the maturation protein gene revealed two genetically different
      group III FRNA subclusters with 36.6% sequence variation. The SC swine lagoon
      isolates were more closely related to group III prototype virus M11, whereas the
      isolates from a swine lagoon in NC, surface waters, and wastewaters grouped with
      prototype virus Q-beta. These results suggest that refining phage genotyping
      systems to discriminate M11-like phages from Q-beta-like phages would not
      necessarily provide greater discriminatory power in distinguishing human from
      animal sources of pollution. Within the group III subclusters, nucleotide
      sequence diversity ranged from 0% to 6.9% for M11-like strains and from 0% to
      8.7% for Q-beta-like strains. It is demonstrated here that nucleotide sequencing
      of closely related FRNA strains can be used to help track sources of
      contamination in surface waters. A similar use of phage genomic sequence
      information to track fecal pollution promises more reliable results than phage
      typing by nucleic acid hybridization and may hold more potential for field
      applications.

PMID- 16461671
TI  - Detection of type A, B, E, and F Clostridium botulinum neurotoxins in foods by
      using an amplified enzyme-linked immunosorbent assay with digoxigenin-labeled
      antibodies.
AB  - An amplified enzyme-linked immunosorbent assay (ELISA) for the detection of
      Clostridium botulinum complex neurotoxins was evaluated for its ability to detect
      these toxins in food. The assay was found to be suitable for detecting type A, B,
      E, and F botulinum neurotoxins in a variety of food matrices representing
      liquids, solid, and semisolid food. Specific foods included broccoli, orange
      juice, bottled water, cola soft drinks, vanilla extract, oregano, potato salad,
      apple juice, meat products, and dairy foods. The detection sensitivity of the
      test for these botulinum complex serotypes was found to be 60 pg/ml (1.9 50%
      lethal dose [LD50]) for botulinum neurotoxin type A (BoNT/A), 176 pg/ml (1.58
      LD50) for BoNT/B, 163 pg/ml for BoNT/E (4.5 LD50), and 117 pg/ml for BoNT/F (less
      than 1 LD50) in casein buffer. The test could also readily detect 2 ng/ml of
      neurotoxins type A, B, E, and F in a variety of food samples. For specificity
      studies, the assay was also used to test a large panel of type A C. botulinum, a
      smaller panel of proteolytic and nonproteolytic type B, E, and F neurotoxin
      producing Clostridia, and nontoxigenic organisms using an overnight incubation of
      toxin production medium. The assay appears to be an effective tool for large
      scale screening of the food supply in the event of a botulinum neurotoxin
      contamination event.

PMID- 16461672
TI  - Isolation and characterization of a cyanophage infecting the toxic cyanobacterium
      Microcystis aeruginosa.
AB  - We isolated a cyanophage (Ma-LMM01) that specifically infects a toxic strain of
      the bloom-forming cyanobacterium Microcystis aeruginosa. Transmission electron
      microscopy showed that the virion is composed of anisometric head and a tail
      complex consisting of a central tube and a contractile sheath with helical
      symmetry. The morphological features and the host specificity suggest that Ma
      LMM01 is a member of the cyanomyovirus group. Using semi-one-step growth
      experiments, the latent period and burst size were estimated to be 6 to 12 h and
      50 to 120 infectious units per cell, respectively. The size of the phage genome
      was estimated to be ca. 160 kbp using pulse-field gel electrophoresis; the
      nucleic acid was sensitive to DNase I, Bal31, and all 14 restriction enzymes
      tested, suggesting that it is a linear double-stranded DNA having a low level of
      methylation. Phylogenetic analyses based on the deduced amino acid sequences of
      two open reading frames coding for ribonucleotide reductase alpha- and beta
      subunits showed that Ma-LMM01 forms a sister group with marine and freshwater
      cyanobacteria and is apparently distinct from T4-like phages. Phylogenetic
      analysis of the deduced amino acid sequence of the putative sheath protein showed
      that Ma-LMM01 does not form a monophyletic group with either the T4-like phages
      or prophages, suggesting that Ma-LMM01 is distinct from other T4-like phages that
      have been described despite morphological similarity. The host-phage system which
      we studied is expected to contribute to our understanding of the ecology of
      Microcystis blooms and the genetics of cyanophages, and our results suggest the
      phages could be used to control toxic cyanobacterial blooms.

PMID- 16461673
TI  - Catabolism of 1,5-anhydro-D-fructose in Sinorhizobium morelense S-30.7.5:
      discovery, characterization, and overexpression of a new 1,5-anhydro-D-fructose
      reductase and its application in sugar analysis and rare sugar synthesis.
AB  - The bacterium Sinorhizobium morelense S-30.7.5 was isolated by a microbial
      screening using the sugar 1,5-anhydro-D-fructose (AF) as the sole carbon source.
      This strain metabolized AF by a novel pathway involving its reduction to 1,5
      anhydro-D-mannitol (AM) and the further conversion of AM to D-mannose by C-1
      oxygenation. Growth studies showed that the AF metabolizing capability is not
      confined to S. morelense S-30.7.5 but is a more common feature among the
      Rhizobiaceae. The AF reducing enzyme was purified and characterized as a new
      NADPH-dependent monomeric reductase (AFR, EC 1.1.1.-) of 35.1 kDa. It catalyzed
      the stereoselective reduction of AF to AM and also the conversion of a number of
      2-keto aldoses (osones) to the corresponding manno-configurated aldoses. In
      contrast, common aldoses and ketoses, as well as nonsugar aldehydes and ketones,
      were not reduced. A database search using the N-terminal AFR sequence retrieved a
      putative 35-kDa oxidoreductase encoded by the open reading frame Smc04400
      localized on the chromosome of Sinorhizobium meliloti 1021. Based on sequence
      information for this locus, the afr gene was cloned from S. morelense S-30.7.5
      and overexpressed in Escherichia coli. In addition to the oxidoreductase of S.
      meliloti 1021, AFR showed high sequence similarities to putative oxidoreductases
      of Mesorhizobium loti, Brucella suis, and B. melitensis but not to any
      oxidoreductase with known functions. AFR could be assigned to the GFO/IDH/MocA
      family on the basis of highly conserved common structural features. His6-tagged
      AFR was used to demonstrate the utility of this enzyme for AF analysis and
      synthesis of AM, as well as related derivatives.

PMID- 16461674
TI  - Root-associated bacteria contribute to mineral weathering and to mineral
      nutrition in trees: a budgeting analysis.
AB  - The principal nutrient source for forest trees derives from the weathering of
      soil minerals which results from water circulation and from plant and microbial
      activity. The main objectives of this work were to quantify the respective
      effects of plant- and root-associated bacteria on mineral weathering and their
      consequences on tree seedling growth and nutrition. That is why we carried out
      two column experiments with a quartz-biotite substrate. The columns were planted
      with or without pine seedlings and inoculated or not with three
      ectomycorrhizosphere bacterial strains to quantify biotite weathering and pine
      growth and to determine how bacteria improve pine growth. We showed that the pine
      roots significantly increased biotite weathering by a factor of 1.3 for magnesium
      and 1.7 for potassium. We also demonstrated that the inoculation of Burkholderia
      glathei PML1(12) significantly increased biotite weathering by a factor of 1.4
      for magnesium and 1.5 for potassium in comparison with the pine alone. In
      addition, we observed a significant positive effect of B. glathei PMB1(7) and
      PML1(12) on pine growth and on root morphology (number of lateral roots and root
      hairs). We demonstrated that PML1(12) improved pine growth when the seedlings
      were supplied with a nutrient solution which did not contain the nutrients
      present in the biotite. No improvement of pine growth was observed when the
      seedlings were supplied with all the nutrients necessary for pine growth. We
      therefore propose that the growth-promoting effect of B. glathei PML1(12) mainly
      resulted from the improved plant nutrition via increased mineral weathering.

PMID- 16461675
TI  - RNA-mediated gene silencing in monokaryons and dikaryons of Schizophyllum
      commune.
AB  - Disruption of genes by homologous recombination occurs at a low frequency in the
      basidiomycete Schizophyllum commune. For instance, the SC3 and SC15 genes were
      inactivated at frequencies of 1 and 5%, respectively. As an alternative to
      disruption, we used gene silencing through the introduction of a hairpin
      construct. The SC15 gene, which encodes an abundantly secreted structural
      protein, was silenced at a frequency of 80% in monokaryons of S. commune after
      introduction of a hairpin construct of the gene. Silencing also occurred in
      dikaryons in which one of the partners was not a silenced strain. The silencing
      mechanism resembles RNAi in other filamentous fungi and is a powerful tool for
      the functional analysis of genes expressed in monokaryons or dikaryons.

PMID- 16461676
TI  - New threshold and confidence estimates for terminal restriction fragment length
      polymorphism analysis of complex bacterial communities.
AB  - Terminal restriction fragment length polymorphism (T-RFLP) analysis has the
      potential to be useful for comparisons of complex bacterial communities,
      especially to detect changes in community structure in response to different
      variables. To do this successfully, systematic variations have to be detected
      above method-associated noise, by standardizing data sets and assigning
      confidence estimates to relationships detected. We investigated the use of
      different standardizing methods in T-RFLP analysis of PCR-amplified 16S rRNA
      genes to elucidate the similarities between the bacterial communities in 17 soil
      and sediment samples. We developed a robust method for standardizing data sets
      that appeared to allow detection of similarities between complex bacterial
      communities. We term this the variable percentage threshold method. We found that
      making conclusions about the similarities of complex bacterial communities from T
      RFLP profiles generated by a single restriction enzyme (RE) may lead to erroneous
      conclusions. Instead, the use of multiple REs, each individually, to generate
      multiple data sets allowed us to determine a confidence estimate for groupings of
      apparently similar communities and at the same time minimized the effects of RE
      selection. In conjunction with the variable percentage threshold method, this
      allowed us to make confident conclusions about the similarities of the complex
      bacterial communities in the 17 different samples.

PMID- 16461677
TI  - Rapid high-throughput assessment of aerobic bacteria in complex samples by
      fluorescence-based oxygen respirometry.
AB  - A simple method has been developed for the analysis of aerobic bacteria in
      complex samples such as broth and food homogenates. It employs commercial
      phosphorescent oxygen-sensitive probes to monitor oxygen consumption of samples
      containing bacteria using standard microtiter plates and fluorescence plate
      readers. As bacteria grow in aqueous medium, at certain points they begin to
      deplete dissolved oxygen, which is seen as an increase in probe fluorescence
      above baseline signal. The time required to reach threshold signal is used to
      either enumerate bacteria based on a predetermined calibration or to assess the
      effects of various effectors on the growth of test bacteria by comparison with an
      untreated control. This method allows for the sensitive (down to a single cell),
      rapid (0.5 to 12 h) enumeration of aerobic bacteria without the need to conduct
      lengthy (48 to 72 h) and tedious colony counts on agar plates. It also allows for
      screening a wide range of chemical and environmental samples for their toxicity.
      These assays have been validated with different bacteria, including Escherichia
      coli, Micrococcus luteus, and Pseudomonas fluorescens, with the enumeration of
      total viable counts in broth and industrial food samples (packaged ham, chicken,
      and mince meat), and comparison with established agar plating and optical-density
      at-600-nm assays has been given.

PMID- 16461678
TI  - Construction and complementation of in-frame deletions of the essential
      Escherichia coli thymidylate kinase gene.
AB  - This work reports the construction of Escherichia coli in-frame deletion strains
      of tmk, which encodes thymidylate kinase, Tmk. The tmk gene is located at the
      third position of a putative five-gene operon at 24.9 min on the E. coli
      chromosome, which comprises the genes pabC, yceG, tmk, holB, and ycfH. To avoid
      potential polar effects on downstream genes of the operon, as well as
      recombination with plasmid-encoded tmk, the tmk gene was replaced by the
      kanamycin resistance gene kka1, encoding amino glycoside 3'-phosphotransferase
      kanamycin kinase. The kanamycin resistance gene is expressed under the control of
      the natural promoter(s) of the putative operon. The E. coli tmk gene is essential
      under any conditions tested. To show functional complementation in bacteria, the
      E. coli tmk gene was replaced by thymidylate kinases of bacteriophage T4 gp1, E.
      coli tmk, Saccharomyces cerevisiae cdc8, or the Homo sapiens homologue, dTYMK.
      Growth of these transgenic E. coli strains is completely dependent on thymidylate
      kinase activities of various origin expressed from plasmids. The substitution
      constructs show no polar effects on the downstream genes holB and ycfH with
      respect to cell viability. The presented transgenic bacteria could be of interest
      for testing of thymidylate kinase-specific phosphorylation of nucleoside
      analogues that are used in therapies against cancer and infectious diseases.

PMID- 16461680
TI  - Cloning and functional characterization of the styE gene, involved in styrene
      transport in Pseudomonas putida CA-3.
AB  - A 1.5-kb region immediately downstream of the styABCD operon involved in styrene
      degradation in Pseudomonas putida CA-3 has been cloned. Sequence analysis
      revealed a 1,296-bp open reading frame, designated styE, and BLAST P database
      comparisons of the deduced StyE amino acid sequence revealed 33 to 98% identity
      with several membrane-associated ATPase-dependent kinase proteins involved in the
      active transport of aromatic hydrocarbons across bacterial membranes and also
      with FadL, an outer membrane protein necessary for the uptake of long-chain fatty
      acids in Escherichia coli. Transcription of styE is styrene dependent, and the
      gene is cotranscribed with the styABCD structural genes. StyE appears to be
      membrane associated, with a corresponding 45.9-kDa band being identified
      following sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of
      membrane preparations from styrene-grown cells. P. putida CA-3 cells in which the
      styE gene had been interrupted were no longer capable of growth on styrene. In
      contrast, overexpression of styE in P. putida CA-3 resulted in a 4.2-fold
      increase in styrene monooxygenase activity compared with wild-type cells grown on
      styrene, with a concomitant 8-fold increase in styA mRNA transcript levels.
      Experiments with the classic, ATPase inhibitor vanadate revealed that growth of
      wild-type cells on styrene was inhibited at a concentration of 1 mM, while 1.75
      mM was required to achieve a similar effect in the StyE overexpression strain.
      Growth of either strain on citrate was not inhibited in the presence of up to 7
      mM vanadate. These findings suggest a role for StyE in the active transport of
      styrene in Pseudomonas putida CA-3 and identify styrene transport as a
      potentially limiting factor with respect to mRNA transcript levels and associated
      enzymatic activity of the styrene degradative pathway.

PMID- 16461679
TI  - Strategy for identification of Bacillus cereus and Bacillus thuringiensis strains
      closely related to Bacillus anthracis.
AB  - Bacillus cereus strains that are genetically closely related to B. anthracis can
      display anthrax-like virulence traits (A. R. Hoffmaster et al., Proc. Natl. Acad.
      Sci. USA 101:8449-8454, 2004). Hence, approaches that rapidly identify these
      "near neighbors" are of great interest for the study of B. anthracis virulence
      mechanisms, as well as to prevent the use of such strains for B. anthracis-based
      bioweapon development. Here, a strategy is proposed for the identification of
      near neighbors of B. anthracis based on single nucleotide polymorphisms (SNP) in
      the 16S-23S rRNA intergenic spacer (ITS) containing tRNA genes, characteristic of
      B. anthracis. By using restriction site insertion-PCR (RSI-PCR) the presence of
      two SNP typical of B. anthracis was screened in 126 B. cereus group strains of
      different origin. Two B. cereus strains and one B. thuringiensis strain showed
      RSI-PCR profiles identical to that of B. anthracis. The sequencing of the entire
      ITS containing tRNA genes revealed two of the strains to be identical to B.
      anthracis. The strict relationship with B. anthracis was confirmed by multilocus
      sequence typing (MLST) of four other independent loci: cerA, plcR, AC-390, and SG
      749. The relationship to B. anthracis of the three strains described by MLST was
      comparable and even higher to that of four B. cereus strains associated with
      periodontitis in humans and previously reported as the closest known strains to
      B. anthracis. SNP in ITS containing tRNA genes combined with RSI-PCR provide a
      very efficient tool for the identification of strains closely related to B.
      anthracis.

PMID- 16461681
TI  - Genetic modification of Bacillus subtilis for production of D-chiro-inositol, an
      investigational drug candidate for treatment of type 2 diabetes and polycystic
      ovary syndrome.
AB  - D-chiro-inositol (DCI) is a drug candidate for the treatment of type 2 diabetes
      and polycystic ovary syndrome, since it improves the efficiency with which the
      body uses insulin and also promotes ovulation. Here, we report genetic
      modification of Bacillus subtilis for production of DCI from myo-inositol (MI).
      The B. subtilis iolABCDEFGHIJ operon encodes enzymes for the multiple steps of
      the MI catabolic pathway. In the first and second steps, MI is converted to 2
      keto-MI (2KMI) by IolG and then to 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione by
      IolE. In this study, we identified iolI encoding inosose isomerase, which
      converts 2KMI to 1-keto-D-chiro-inositol (1KDCI), and found that IolG reduces
      1KDCI to DCI. Inactivation of iolE in a mutant constitutively expressing the iol
      operon blocked the MI catabolic pathway to accumulate 2KMI, which was converted
      to DCI via the activity of IolI and IolG. The mutant was able to convert at least
      6% of input MI in the culture medium to DCI.

PMID- 16461682
TI  - Natural transformation-mediated transfer of erythromycin resistance in
      Campylobacter coli strains from turkeys and swine.
AB  - Erythromycin resistance in Campylobacter coli from meat animals is frequently
      encountered and could represent a substantial barrier to antibiotic treatment of
      human infections. Erythromycin resistance in this organism has been associated
      with a point mutation (A2075G) in the 23S rRNA gene. However, the mechanisms
      responsible for possible dissemination of erythromycin resistance in C. coli
      remain poorly understood. In this study, we investigated transformation-mediated
      acquisition of erythromycin resistance by genotypically diverse C. coli strains
      from turkeys and swine, with total genomic DNA from erythromycin-resistant C.
      coli of either turkey or swine origin used as a donor. Overall, transformation to
      erythromycin resistance was significantly more frequent in C. coli strains from
      turkeys than in swine-derived strains (P < 0.01). The frequency of transformation
      to erythromycin resistance was 10(-5) to 10(-6) for turkey-derived strains but
      10(-7) or less for C. coli from swine. Transformants harbored the point mutation
      A2075G in the 23S rRNA gene, as did the erythromycin-resistant strains used as
      DNA donors. Erythromycin resistance was stable in transformants following serial
      transfers in the absence of the antibiotic, and most transformants had high MICs
      (>256 microg/ml), as did the C. coli donor strains. In contrast to the results
      obtained with transformation, spontaneous mutants had relatively low erythromycin
      MICs (32 to 64 microg/ml) and lacked the A2075G mutation in the 23S rRNA gene.
      These findings suggest that natural transformation has the potential to
      contribute to the dissemination of high-level resistance to erythromycin among C.
      coli strains colonizing meat animals.

PMID- 16461683
TI  - Evidence for autotrophy via the reverse tricarboxylic acid cycle in the marine
      magnetotactic coccus strain MC-1.
AB  - Strain MC-1 is a marine, microaerophilic, magnetite-producing, magnetotactic
      coccus phylogenetically affiliated with the alpha-Proteobacteria. Strain MC-1
      grew chemolithotrophically with sulfide and thiosulfate as electron donors with
      HCO3-/CO2 as the sole carbon source. Experiments with cells grown
      microaerobically in liquid with thiosulfate and H14CO3-/14CO2 showed that all
      cell carbon was derived from H14CO3-/14CO2 and therefore that MC-1 is capable of
      chemolithoautotrophy. Cell extracts did not exhibit ribulose-1,5-bisphosphate
      carboxylase-oxygenase (RubisCO) activity, nor were RubisCO genes found in the
      draft genome of MC-1. Thus, unlike other chemolithoautotrophic, magnetotactic
      bacteria, strain MC-1 does not appear to utilize the Calvin-Benson-Bassham cycle
      for autotrophy. Cell extracts did not exhibit carbon monoxide dehydrogenase
      activity, indicating that the acetyl-coenzyme A pathway also does not function in
      strain MC-1. The 13C content of whole cells of MC-1 relative to the 13C content
      of the inorganic carbon source (Deltadelta13C) was -11.4 per thousand. Cellular
      fatty acids showed enrichment of 13C relative to whole cells. Strain MC-1 cell
      extracts showed activities for several key enzymes of the reverse (reductive)
      tricarboxylic acid (rTCA) cycle including fumarate reductase, pyruvate:acceptor
      oxidoreductase and 2-oxoglutarate:acceptor oxidoreductase. Although ATP citrate
      lyase (another key enzyme of the rTCA cycle) activity was not detected in strain
      MC-1 using commonly used assays, cell extracts did cleave citrate, and the
      reaction was dependent upon the presence of ATP and coenzyme A. Thus, we infer
      the presence of an ATP-dependent citrate-cleaving mechanism. These results are
      consistent with the operation of the rTCA cycle in MC-1. Strain MC-1 appears to
      be the first known representative of the alpha-Proteobacteria to use the rTCA
      cycle for autotrophy.

PMID- 16461684
TI  - Involvement of two specific causes of cell mortality in freeze-thaw cycles with
      freezing to -196 degrees C.
AB  - The purpose of this study was to examine cell viability after freezing. Two
      distinct ranges of temperature were identified as corresponding to stages at
      which yeast cell mortality occurred during freezing to -196 degrees C. The upper
      temperature range was related to the temperature of crystallization of the
      medium, which was dependent on the solute concentration; in this range mortality
      was prevented by high solute concentrations, and the proportion of the medium in
      the vitreous state was greater than the proportion in the crystallized state. The
      lower temperature range was related to recrystallization that occurred during
      thawing. Mortality in this temperature range was increased by a high cooling rate
      and/or high solute concentration in the freezing medium and a low temperature
      (less than -70 degrees C). However, a high rate of thawing prevented yeast
      mortality in this lower temperature range. Overall, it was found that cell
      viability could be conserved better under freezing conditions by increasing the
      osmotic pressure of the medium and by using an increased warming rate.

PMID- 16461686
TI  - Differential effects of nitrogenous fertilizers on methane-consuming microbes in
      rice field and forest soils.
AB  - The impact of environmental perturbation (e.g., nitrogenous fertilizers) on the
      dynamics of methane fluxes from soils and wetland systems is poorly understood.
      Results of fertilizer studies are often contradictory, even within similar
      ecosystems. In the present study the hypothesis of whether these contradictory
      results may be explained by the composition of the methane-consuming microbial
      community and hence whether methanotrophic diversity affects methane fluxes was
      investigated. To this end, rice field and forest soils were incubated in
      microcosms and supplemented with different nitrogenous fertilizers and methane
      concentrations. By labeling the methane with 13C, diversity and function could be
      coupled by analyses of phospholipid-derived fatty acids (PLFA) extracted from the
      soils at different time points during incubation. In both rice field and forest
      soils, the activity as well as the growth rate of methane-consuming bacteria was
      affected differentially. For type I methanotrophs, fertilizer application
      stimulated the consumption of methane and the subsequent growth, while type II
      methanotrophs were generally inhibited. Terminal restriction fragment length
      polymorphism analyses of the pmoA gene supported the PLFA results. Multivariate
      analyses of stable-isotope-probing PLFA profiles indicated that in forest and
      rice field soils, Methylocystis (type II) species were affected by fertilization.
      The type I methanotrophs active in forest soils (Methylomicrobium/Methylosarcina
      related) differed from the active species in rice field soils
      (Methylobacter/Methylomonas related). Our results provide a case example showing
      that microbial community structure indeed matters, especially when assessing and
      predicting the impact of environmental change on biodiversity loss and ecosystem
      functioning.

PMID- 16461685
TI  - Several archaeal homologs of putative oligopeptide-binding proteins encoded by
      Thermotoga maritima bind sugars.
AB  - The hyperthermophilic bacterium Thermotoga maritima has shared many genes with
      archaea through horizontal gene transfer. Several of these encode putative
      oligopeptide ATP binding cassette (ABC) transporters. We sought to test the
      hypothesis that these transporters actually transport sugars by measuring the
      substrate affinities of their encoded substrate-binding proteins (SBPs). This
      information will increase our understanding of the selective pressures that
      allowed this organism to retain these archaeal homologs. By measuring changes in
      intrinsic fluorescence of these SBPs in response to exposure to various sugars,
      we found that five of the eight proteins examined bind to sugars. We could not
      identify the ligands of the SBPs TM0460, TM1150, and TM1199. The ligands for the
      archaeal SBPs are TM0031 (BglE), the beta-glucosides cellobiose and
      laminaribiose; TM0071 (XloE), xylobiose and xylotriose; TM0300 (GloE), large
      glucose oligosaccharides represented by xyloglucans; TM1223 (ManE), beta-1,4
      mannobiose; and TM1226 (ManD), beta-1,4-mannobiose, beta-1,4-mannotriose, beta
      1,4-mannotetraose, beta-1,4-galactosyl mannobiose, and cellobiose. For
      comparison, seven bacterial putative sugar-binding proteins were examined and
      ligands for three (TM0595, TM0810, and TM1855) were not identified. The ligands
      for these bacterial SBPs are TM0114 (XylE), xylose; TM0418 (InoE), myo-inositol;
      TM0432 (AguE), alpha-1,4-digalactouronic acid; and TM0958 (RbsB), ribose. We
      found that T. maritima does not grow on several complex polypeptide mixtures as
      sole sources of carbon and nitrogen, so it is unlikely that these archaeal ABC
      transporters are used primarily for oligopeptide transport. Since these SBPs bind
      oligosaccharides with micromolar to nanomolar affinities, we propose that they
      are used primarily for oligosaccharide transport.

PMID- 16461687
TI  - Unstable lysogeny and pseudolysogeny in Vibrio harveyi siphovirus-like phage 1.
AB  - Exposure of Vibrio harveyi (strain VH1114) to V. harveyi siphovirus-like phage 1
      (VHS1) resulted in the production of a low percentage of lysogenized clones of
      variable stability. These were retrieved most easily as small colonies within dot
      plaques. Analysis revealed that VHS1 prophage was most likely carried by VH1114
      as an episome rather than integrated into the host chromosome. In the late
      exponential growth phase, lysogenized VH1114 continuously produced VHS1 but also
      gave rise to a large number of cured progeny. The absence of phage DNA in the
      cured progeny was confirmed by the absence of VHS1 DNA in Southern blot and PCR
      assays. Curiously, these very stable, cured subclones did not show the parental
      phenotype of clear plaques with VHS1 but instead showed turbid plaques, both in
      overlaid lawns and in dot plaque assays. This phenotypic difference from the
      original parental isolate suggested that transient lysogeny by VHS1 had resulted
      in a stable genetic change in the cured clones. Such clones may be called
      pseudolysogens (i.e., false lysogens), since they have undergone transient
      lysogeny and have retained some resistance to full lytic phage development,
      despite the loss of viable or detectable prophage.

PMID- 16461688
TI  - Identification of a Thiomicrospira denitrificans-like epsilonproteobacterium as a
      catalyst for autotrophic denitrification in the central Baltic Sea.
AB  - Identification and functional analysis of key members of bacterial communities in
      marine and estuarine environments are major challenges for obtaining a
      mechanistic understanding of biogeochemical processes. In the Baltic Sea basins,
      as in many other marine environments with anoxic bodies of water, the oxic-anoxic
      interface is considered a layer of high bacterial turnover of sulfur, nitrogen,
      and carbon compounds that has a great impact on matter balances in the whole
      ecosystem. We focused on autotrophic denitrification by oxidation of reduced
      sulfur compounds as a biogeochemically important process mediating concomitant
      turnover of sulfur, nitrogen, and carbon. We used a newly developed approach
      consisting of molecular analyses in stimulation experiments and in situ
      abundance. The molecular approach was based on single-strand conformational
      polymorphism (SSCP) analysis of the bacterial community RNA, which allowed
      identification of potential denitrifiers based on the sequences of enhanced SSCP
      bands and monitoring of the overall bacterial community during the experiments.
      Sequences of the SSCP bands of interest were used to design highly specific
      primers that enabled (i) generation of almost complete 16S rRNA gene sequences
      using experimental and environmental DNA as templates and (ii) quantification of
      the bacteria of interest by real-time PCR. By using this approach we identified
      the bacteria responsible for autotrophic denitrification as a single taxon, an
      epsilonproteobacterium related to the autotrophic denitrifier Thiomicrospira
      denitrificans. This finding was confirmed by material balances in the experiments
      that were consistent with those obtained with continuous cultures of T.
      denitrificans. The presence and activity of a bacterium that is phylogenetically
      and physiologically closely related to T. denitrificans could be relevant for the
      carbon budget of the central Baltic Sea because T. denitrificans exhibits only
      one-half the efficiency for carbon dioxide fixation per mol of sulfide oxidized
      and mol of nitrate reduced of Thiobacillus denitrificans hypothesized previously
      for this function.

PMID- 16461689
TI  - Neutral lipid biosynthesis in engineered Escherichia coli: jojoba oil-like wax
      esters and fatty acid butyl esters.
AB  - Wax esters are esters of long-chain fatty acids and long-chain fatty alcohols
      which are of considerable commercial importance and are produced on a scale of 3
      million tons per year. The oil from the jojoba plant (Simmondsia chinensis) is
      the main biological source of wax esters. Although it has a multitude of
      potential applications, the use of jojoba oil is restricted, due to its high
      price. In this study, we describe the establishment of heterologous wax ester
      biosynthesis in a recombinant Escherichia coli strain by coexpression of a fatty
      alcohol-producing bifunctional acyl-coenzyme A reductase from the jojoba plant
      and a bacterial wax ester synthase from Acinetobacter baylyi strain ADP1,
      catalyzing the esterification of fatty alcohols and coenzyme A thioesters of
      fatty acids. In the presence of oleate, jojoba oil-like wax esters such as
      palmityl oleate, palmityl palmitoleate, and oleyl oleate were produced, amounting
      to up to ca. 1% of the cellular dry weight. In addition to wax esters, fatty acid
      butyl esters were unexpectedly observed in the presence of oleate. The latter
      could be attributed to solvent residues of 1-butanol present in the medium
      component, Bacto tryptone. Neutral lipids produced in recombinant E. coli were
      accumulated as intracytoplasmic inclusions, demonstrating that the formation and
      structural integrity of bacterial lipid bodies do not require specific structural
      proteins. This is the first report on substantial biosynthesis and accumulation
      of neutral lipids in E. coli, which might open new perspectives for the
      biotechnological production of cheap jojoba oil equivalents from inexpensive
      resources employing recombinant microorganisms.

PMID- 16461690
TI  - Comparison of the efficacies of disinfectants to control microbial contamination
      in dental unit water systems in general dental practices across the European
      Union.
AB  - Water delivered by dental unit water systems (DUWS) in general dental practices
      can harbor high numbers of bacteria, including opportunistic pathogens. Biofilms
      on tubing within DUWS provide a reservoir for microorganisms and should be
      controlled. This study compared disinfection products for their ability to meet
      the American Dental Association's guideline of <200 CFU x ml(-1) for DUWS water.
      Alpron, BioBlue, Dentosept, Oxygenal, Sanosil, Sterilex Ultra, and Ster4Spray
      were tested in DUWS (n = 134) in Denmark, Germany, Greece, Ireland, The
      Netherlands, Spain, and the United Kingdom. Weekly water samples were tested for
      total viable counts (TVCs) on yeast extract agar, and, where possible, the
      effects of products on established biofilm (TVCs) were measured. A 4- to 5-week
      baseline measurement period was followed by 6 to 8 weeks of disinfection
      (intermittent or continuous product application). DUWS water TVCs before
      disinfection ranged from 0 to 5.41 log CFU x ml(-1). Disinfectants achieved
      reductions in the median water TVC ranging from 0.69 (Ster4Spray) to 3.11
      (Dentosept) log CFU x ml(-1), although occasional high values (up to 4.88 log CFU
      x ml(-1)) occurred with all products. Before treatment, 64% of all baseline
      samples exceeded American Dental Association guidelines, compared to only 17%
      following commencement of treatment; where tested, biofilm TVCs were reduced to
      below detectable levels. The antimicrobial efficacies of products varied (e.g.,
      91% of water samples from DUWS treated with Dentosept or Oxygenal met American
      Dental Association guidelines, compared to 60% of those treated with Ster4Spray).
      Overall, the continuously applied products performed better than those applied
      intermittently. The most effective products were Dentosept and Oxygenal, although
      Dentosept gave the most consistent and sustained antimicrobial effect over time.

PMID- 16461691
TI  - Host-symbiont relationships in hydrothermal vent gastropods of the genus
      Alviniconcha from the Southwest Pacific.
AB  - Hydrothermal vent gastropods of the genus Alviniconcha are unique among metazoans
      in their ability to derive their nutrition from chemoautotrophic gamma- and
      epsilon-proteobacterial endosymbionts. Although host-symbiont relationships in
      Alviniconcha gastropods from the Central Indian Ridge in the Indian Ocean and the
      Mariana Trough in the Western Pacific have been studied extensively, host
      symbiont relationships in Alviniconcha gastropods from the Southwest Pacific
      remain largely unknown. Phylogenetic analysis using mitochondrial cytochrome c
      oxidase subunit I gene sequences of host gastropods from the Manus, North Fiji,
      and Lau Back-Arc Basins in the Southwest Pacific has revealed a new host lineage
      in a Alviniconcha gastropod from the Lau Basin and the occurrence of the host
      lineage Alviniconcha sp. type 2 in the Manus Basin. Based on 16S rRNA gene
      sequences of bacterial endosymbionts, two gamma-proteobacterial lineages and one
      epsilon-proteobacterial lineage were identified in the present study. The carbon
      isotopic compositions of the biomass and fatty acids of the gastropod tissues
      suggest that the gamma- and epsilon-proteobacterial endosymbionts mediate the
      Calvin-Benson cycle and the reductive tricarboxylic acid cycle, respectively, for
      their chemoautotrophic growth. Coupling of the host and symbiont lineages from
      the three Southwest Pacific basins revealed that each of the Alviniconcha
      lineages harbors different bacterial endosymbionts belonging to either the gamma-
      or epsilon-Proteobacteria. The host specificity exhibited in symbiont selection
      provides support for the recognition of each of the host lineages as a distinct
      species. The results from the present study also suggest the possibility that
      Alviniconcha sp. types 1 and 2 separately inhabit hydrothermal vent sites
      approximately 120 m apart in the North Fiji Basin and 500 m apart in the Manus
      Basin.

PMID- 16461692
TI  - The thin pili of Acinetobacter sp. strain BD413 mediate adhesion to biotic and
      abiotic surfaces.
AB  - Two structurally different appendages, thin and thick pili, are found in members
      of the genus Acinetobacter. The presence of pilus structures correlates with
      different phenotypes, such as adherence to surfaces, a trait not only observed in
      pathogenic Acinetobacter species, as well as motility. However, their distinct
      individual roles were unknown. To characterize the role of different pili in the
      physiology of Acinetobacter, we isolated the thin pili from the cell surface of
      Acinetobacter sp. strain BD413 (recently recognized as representative of
      Acinetobacter baylyi), a soil bacterium that rapidly takes up naked DNA from its
      environment. Electron microscopy revealed that the pilus has an external diameter
      of 2 to 3 nm for single filaments. The filaments are packed into right-handed
      bundles. The major protein constituting the pilus was purified, and the encoding
      gene, acuA, was cloned. AcuA was found to be weakly related to the structural
      subunit of F17 pili of Escherichia coli. Analyses of the acuA flanking DNA region
      led to the identification of three closely associated genes, acuD, acuC, and
      acuG, whose deduced proteins are similar to chaperone, usher, and adhesin of F17
      related pili, respectively. Transcriptional analyses revealed that acuA
      expression is maximal in the late-stationary-growth phase. Mutation of acuA led
      to a loss of thin pili and concomitantly loss of adhesion to polystyrene and
      erythrocytes but not loss of competence. Therefore, thin pili of Acinetobacter
      sp. strain BD413 are suggested to be assembled by the chaperone/usher pathway and
      are involved in adherence to biotic and abiotic surfaces.

PMID- 16461693
TI  - Glutamate dehydrogenase activity can be transmitted naturally to Lactococcus
      lactis strains to stimulate amino acid conversion to aroma compounds.
AB  - Amino acid conversion to aroma compounds by Lactococcus lactis is limited by the
      low production of alpha-ketoglutarate that is necessary for the first step of
      conversion. Recently, glutamate dehydrogenase (GDH) activity that catalyzes the
      reversible glutamate deamination to alpha-ketoglutarate was detected in L. lactis
      strains isolated from a vegetal source, and the gene responsible for the activity
      in L. lactis NCDO1867 was identified and characterized. The gene is located on a
      70-kb plasmid also encoding cadmium resistance. In this study, gdh gene
      inactivation and overexpression confirmed the direct impact of GDH activity of L.
      lactis on amino acid catabolism in a reaction medium at pH 5.5, the pH of cheese.
      By using cadmium resistance as a selectable marker, the plasmid carrying gdh was
      naturally transmitted to another L. lactis strain by a mating procedure. The
      transfer conferred to the host strain GDH activity and the ability to catabolize
      amino acids in the presence of glutamate in the reaction medium. However, the
      plasmid appeared unstable in a strain also containing the protease lactose
      plasmid pLP712, indicating an incompatibility between these two plasmids.

PMID- 16461694
TI  - Engineering the genotype of Acinetobacter sp. strain ADP1 to enhance biosynthesis
      of cyanophycin.
AB  - To study the importance of arginine provision and phosphate limitation for
      synthesis and accumulation of cyanophycin (CGP) in Acinetobacter sp. strain ADP1,
      genes encoding the putative arginine regulatory protein (argR) and the arginine
      succinyltransferase (astA) were inactivated, and the effects of these mutations
      on CGP synthesis were analyzed. The inactivation of these genes resulted in a 3.5
      or 7-fold increase in CGP content, respectively, when the cells were grown on
      glutamate. Knockout mutations in both genes led to a better understanding of the
      effect of the addition of other substrates to arginine on CGP synthesis during
      growth of the cells of Acinetobacter sp. strain ADP1. Overexpression of ArgF
      (ornithine carbamoyltransferase), CarA-CarB (small and large subunits of
      carbamoylphosphate synthetase), and PepC (phosphoenolpyruvate carboxylase)
      triggered synthesis of CGP if amino acids were used as a carbon source whereas it
      was not triggered by gluconate or other sugars. Cells of Acinetobacter sp. strain
      ADP1, which is largely lacking genes for carbohydrate metabolism, showed a
      significant increase in CGP contents when grown on mineral medium supplemented
      with glutamate, aspartate, or arginine. The Acinetobacter sp. DeltaastA(pYargF)
      strain is unable to utilize arginine but synthesizes more arginine, resulting in
      CGP contents as high as 30% and 25% of cell dry matter when grown on protamylasse
      or Luria-Bertani medium, respectively. This recombinant strain overcame the
      bottleneck of the costly arginine provision where it produces about 75% of the
      CGP obtained from the parent cells grown on mineral medium containing pure
      arginine as the sole source of carbon. Phosphate starvation is the only known
      trigger for CGP synthesis in this bacterium, which possesses the PhoB/PhoR
      phosphate regulon system. Overexpression of phoB caused an 8.6-fold increase in
      CGP content in comparison to the parent strain at a nonlimiting phosphate
      concentration.

PMID- 16461695
TI  - First insights into the evolution of Streptococcus uberis: a multilocus sequence
      typing scheme that enables investigation of its population biology.
AB  - Intramammary infection with Streptococcus uberis is a common cause of bovine
      mastitis throughout the world. Several procedures to differentiate S. uberis
      isolates have been proposed. However, all are prone to interlaboratory variation,
      and none is suitable for the description of the population structure. We describe
      here the development of a multilocus sequence typing (MLST) scheme for S. uberis
      to help address these issues. The sequences of seven housekeeping gene fragments
      from each of 160 United Kingdom milk isolates of S. uberis were determined.
      Between 5 and 17 alleles were obtained per locus, giving the potential to
      discriminate between 1.3 x 10(7) sequence types. In this study, 57 sequence types
      (STs) were identified. Statistical comparisons between the maximum-likelihood
      trees constructed by using the seven housekeeping gene fragments showed that the
      congruence was no better than that between each tree and trees of random
      topology, indicating there had been significant recombination within these loci.
      The population contained one major lineage (designated the ST-5 complex). This
      dominated the population, containing 24 STs and representing 112 isolates. The
      other 33 STs were not assigned to any clonal complex. All of the isolates in the
      ST-5 lineage carried hasA, a gene that is essential for capsule production. There
      was no clear association between ST or clonal complex and disease. The S. uberis
      MLST system offers researchers a valuable tool that allows further investigation
      of the population biology of this organism and insights into the epidemiology of
      this disease on a global scale.

PMID- 16461696
TI  - Application of Streptococcus uberis multilocus sequence typing: analysis of the
      population structure detected among environmental and bovine isolates from New
      Zealand and the United Kingdom.
AB  - We recently developed a multilocus sequence typing (MLST) scheme to differentiate
      S. uberis isolates and facilitate an understanding of the population biology of
      this pathogen. The scheme was initially used to study a collection of 160 bovine
      milk isolates from the United Kingdom and showed that the majority of isolates
      were from one clonal complex (designated the ST-5 complex). Here we describe the
      MLST analysis of a collection of New Zealand isolates. These were obtained from
      diverse sources, including bovine milk, other bovine anatomical sites, and
      environmental sources. The complete allelic profiles of 253 isolates were
      determined. The collection was highly diverse and included 131 different sequence
      types (STs). The New Zealand and United Kingdom populations were distinct, since
      none of the 131 STs were represented within the previously studied collection of
      160 United Kingdom S. uberis isolates. However, seven of the STs were members of
      the ST-5 clonal complex, the major complex within the United Kingdom collection.
      Two new clonal complexes were identified: ST-143 and ST-86. All three major
      complexes were isolated from milk, other bovine sites, and the environment.
      Carriage of the hasA gene, which is necessary for capsule formation, correlated
      with clonal complex and isolation from clinical cases of mastitis.

PMID- 16461697
TI  - Degradation of 2,3-diethyl-5-methylpyrazine by a newly discovered bacterium,
      Mycobacterium sp. strain DM-11.
AB  - A bacterium was isolated from the waste gas treatment plant at a fishmeal
      processing company on the basis of its capacity to use 2,3-diethyl-5
      methylpyrazine (DM) as a sole carbon and energy source. The strain, designated
      strain DM-11, grew optimally at 25 degrees C and had a doubling time of 29.2 h.
      The strain did not grow on complex media like tryptic soy broth, Luria-Bertani
      broth, or nutrient broth or on simple carbon sources like glucose, acetate,
      oxoglutarate, succinate, or citrate. Only on Lowenstein-Jensen medium was growth
      observed. The 16S rRNA gene sequence of strain DM-11 showed the highest
      similarity (96.2%) to Mycobacterium poriferae strain ATCC 35087T. Therefore,
      strain DM-11 merits recognition as a novel species within the genus
      Mycobacterium. DM also served as a sole nitrogen source for the growth of strain
      DM-11. The degradation of DM by strain DM-11 requires molecular oxygen. The first
      intermediate was identified as 5,6-diethyl-2-hydroxy-3-methylpyrazine (DHM). Its
      disappearance was accompanied by the release of ammonium into the culture medium.
      No other metabolite was detected. We conclude that ring fission occurred directly
      after the formation of DHM and ammonium was eliminated after ring cleavage.
      Molecular oxygen was essential for the degradation of DHM. The expression of
      enzymes involved in the degradation of DM and DHM was regulated. Only cells
      induced by DM or DHM converted these compounds. Strain DM-11 also grew on 2-ethyl
      5(6)-methylpyrazine (EMP) and 2,3,5-trimethylpyrazine (TMP) as a sole carbon,
      nitrogen, and energy source. In addition, the strain converted many pyrazines
      found in the waste gases of food industries cometabolically.

PMID- 16461698
TI  - In situ and in vitro gene expression by Vibrio vulnificus during entry into,
      persistence within, and resuscitation from the viable but nonculturable state.
AB  - Isolation of Vibrio vulnificus during winter months is difficult due to the
      entrance of these cells into the viable but nonculturable (VBNC) state. While
      several studies have investigated in vitro gene expression upon entrance into and
      persistence within the VBNC state, to our knowledge, no in situ studies have been
      reported. We incubated clinical and environmental isolates of V. vulnificus in
      estuarine waters during winter months to monitor the expression of several genes
      during the VBNC state and compared these to results from in vitro studies. katG
      (periplasmic catalase) was down-regulated during the VBNC state in vitro and in
      situ compared to the constitutively expressed gene tufA. Our results indicate
      that the loss of catalase activity we previously reported is a direct result of
      katG repression, which likely accounts for the VBNC response of this pathogen.
      While expression of vvhA (hemolysin) was detectable in environmental strains
      during in situ incubation, it ceased in all cases by ca. 1 h. These results
      suggest that the natural role of hemolysin in V. vulnificus may be in
      osmoprotection and/or the cold shock response. Differences in expression of the
      capsular genes wza and wzb were observed in the two recently reported genotypes
      of this species. Expression of rpoS, encoding the stress sigma factor RpoS, was
      continuous upon entry into the VBNC state during both in situ and in vitro
      studies. We found the half-life of mRNA to be less than 60 minutes, confirming
      that mRNA detection in these VBNC cells is a result of de novo RNA synthesis.

PMID- 16461699
TI  - Phosphorus scavenging in the unicellular marine diazotroph Crocosphaera watsonii.
AB  - Through the fixation of atmospheric nitrogen and photosynthesis, marine
      diazotrophs play a critical role in the global cycling of nitrogen and carbon.
      Crocosphaera watsonii is a recently described unicellular diazotroph that may
      significantly contribute to marine nitrogen fixation in tropical environments.
      One of the many factors that can constrain the growth and nitrogen fixation rates
      of marine diazotrophs is phosphorus bioavailability. Using genomic and
      physiological approaches, we examined phosphorus scavenging mechanisms in strains
      of C. watsonii from both the Atlantic and the Pacific. Observations from the C.
      watsonii WH8501 genome suggest that this organism has the capacity for high
      affinity phosphate transport (e.g., homologs of pstSCAB) in low-phosphate,
      oligotrophic systems. The pstS gene (high-affinity phosphate binding) is present
      in strains isolated from both the Atlantic and the Pacific, and its expression
      was regulated by the exogenous phosphate supply in strain WH8501. Genomic
      observation also indicated a broad capacity for phosphomonoester hydrolysis
      (e.g., a putative alkaline phosphatase). In contrast, no clear homologs of genes
      for phosphonate transport and hydrolysis could be identified. Consistent with
      these genomic observations, C. watsonii WH8501 is able to grow on
      phosphomonoesters as a sole source of added phosphorus but not on the
      phosphonates tested to date. Taken together these data suggest that C. watsonii
      has a robust capacity for scavenging phosphorus in oligotrophic systems, although
      this capacity differs from that of other marine cyanobacterial genera, such as
      Synechococcus, Prochlorococcus, and Trichodesmium.

PMID- 16461700
TI  - Production of the lantibiotic salivaricin A and its variants by oral streptococci
      and use of a specific induction assay to detect their presence in human saliva.
AB  - Salivaricin A (SalA), the first Streptococcus salivarius lantibiotic to be
      characterized, appears to be inhibitory to most Streptococcus pyogenes strains. A
      variant of the SalA structural gene (salA1) is present in more than 90% of S.
      pyogenes strains, but only strains of M serotype 4 and T pattern 4 produce the
      biologically active peptide. The present study identifies four additional
      variants (salA2 to salA5) of the SalA structural gene and demonstrates that each
      of the corresponding inhibitory peptides (SalA2 to SalA5) is produced in vitro.
      These variants appear to be similar to SalA and SalA1 in their inhibitory
      activity against Micrococcus luteus and in their ability to act as inducers of
      SalA production. It had previously been shown that S. pyogenes strain SF370 had a
      deletion (of approximately 2.5 kb) in the salM and salT genes of the salA1 locus.
      In the present study, several additional characteristic deletions within the
      salA1 loci were identified. S. pyogenes strains of the same M serotype all share
      the same salA1 locus structure. Since S. salivarius is a predominant member of
      the normal oral flora of healthy humans, strains producing anti-S. pyogenes
      lantibiotics, such as SalA, may have excellent potential for use as oral
      probiotics. In the present study, we have used a highly specific SalA induction
      system to directly detect the presence of SalA in the saliva of humans who either
      naturally harbor populations of SalA-producing S. salivarius or who have been
      colonized with the SalA2-producing probiotic S. salivarius K12.

PMID- 16461701
TI  - A novel Bacteroidetes symbiont is localized in Scaphoideus titanus, the insect
      vector of Flavescence doree in Vitis vinifera.
AB  - Flavescence doree (FD) is a grapevine disease that afflicts several wine
      production areas in Europe, from Portugal to Serbia. FD is caused by a bacterium,
      "Candidatus Phytoplasma vitis," which is spread throughout the vineyards by a
      leafhopper, Scaphoideus titanus (Cicadellidae). After collection of S. titanus
      specimens from FD-contaminated vineyards in three different areas in the Piedmont
      region of Italy, we performed a survey to characterize the bacterial microflora
      associated with this insect. Using length heterogeneity PCR with universal
      primers for bacteria we identified a major peak associated with almost all of the
      individuals examined (both males and females). Characterization by denaturing
      gradient gel electrophoresis confirmed the presence of a major band that, after
      sequencing, showed a 97 to 99% identity with Bacteroidetes symbionts of the
      "Candidatus Cardinium hertigii" group. In addition, electron microscopy of
      tissues of S. titanus fed for 3 months on phytoplasma-infected grapevine plants
      showed bacterial cells with the typical morphology of "Ca. Cardinium hertigii."
      This endosymbiont, tentatively designated ST1-C, was found in the cytoplasm of
      previtellogenic and vitellogenic ovarian cells, in the follicle cells, and in the
      fat body and salivary glands. In addition, cell morphologies resembling those of
      "Ca. Phytoplasma vitis" were detected in the midgut, and specific PCR assays
      indicated the presence of the phytoplasma in the gut, fat body and salivary
      glands. These results indicate that ST1-C and "Ca. Phytoplasma vitis" have a
      complex life cycle in the body of S. titanus and are colocalized in different
      organs and tissues.

PMID- 16461702
TI  - Degradation of 4-chloro-2-methylphenoxyacetic acid in top- and subsoil is
      quantitatively linked to the class III tfdA gene.
AB  - The tfdA gene is known to be involved in the first step of the degradation of the
      phenoxy acid herbicide 4-chloro-2-methylphenoxyacetic acid (MCPA) in several soil
      bacteria, but bacteria containing other tfdA-like genes have been isolated as
      well. A quantitative real-time PCR method was used to monitor the increase in the
      concentration of tfdA genes during degradation of MCPA in sandy topsoil and
      subsoil over a period of 115 days. Quantitative PCR revealed growth in the tfdA
      containing bacterial community, from 500 genes g(-1) soil to approximately 3 x
      10(4) genes g(-1) soil and to 7 x 10(5) genes g(-1) soil for topsoil initially
      added to 2.3 mg MCPA kg(-1) (dry weight) soil and 20 mg MCPA kg(-1) (dry weight)
      soil, respectively. We analyzed the diversity of the tfdA gene during the
      degradation experiment. Analyses of melting curves of real-time PCR amplification
      products showed that a shift in the dominant tfdA population structure occurred
      during the degradation period. Further denaturing gradient gel electrophoresis
      and sequence analysis revealed that the tfdA genes responsible for the
      degradation of MCPA belonged to the class III tfdA genes, while the tfdA genes
      present in the soil before the occurrence of degradation belonged to the class I
      tfdA genes. The implications of these results is that the initial assessment of
      functional genes in soils does not necessarily reflect the organisms or genes
      that would carry out the degradation of the compounds in question.

PMID- 16461703
TI  - Pyrroloquinoline quinone-dependent dehydrogenases from Ketogulonicigenium vulgare
      catalyze the direct conversion of L-sorbosone to L-ascorbic acid.
AB  - A novel enzyme, L-sorbosone dehydrogenase 1 (SNDH1), which directly converts L
      sorbosone to L-ascorbic acid (L-AA), was isolated from Ketogulonicigenium vulgare
      DSM 4025 and characterized. This enzyme was a homooligomer of 75-kDa subunits
      containing pyrroloquinoline quinone (PQQ) and heme c as the prosthetic groups.
      Two isozymes of SNDH, SNDH2 consisting of 75-kDa and 55-kDa subunits and SNDH3
      consisting of 55-kDa subunits, were also purified from the bacterium. All of the
      SNDHs produced L-AA, as well as 2-keto-L-gulonic acid (2KGA), from L-sorbosone,
      suggesting that tautomerization of L-sorbosone causes the dual conversion by
      SNDHs. The sndH gene coding for SNDH1 was isolated and analyzed. The N-terminal
      four-fifths of the SNDH amino acid sequence exhibited 40% identity to the
      sequence of a soluble quinoprotein glucose dehydrogenase from Acinetobacter
      calcoaceticus. The C-terminal one-fifth of the sequence exhibited similarity to a
      c-type cytochrome with a heme-binding motif. A lysate of Escherichia coli cells
      expressing sndH exhibited SNDH activity in the presence of PQQ and CaCl2. Gene
      disruption analysis of K. vulgare indicated that all of the SNDH proteins are
      encoded by the sndH gene. The 55-kDa subunit was derived from the 75-kDa subunit,
      as indicated by cleavage of the C-terminal domain in the bacterial cells.

PMID- 16461704
TI  - Paenibacillus sp. strain JDR-2 and XynA1: a novel system for methylglucuronoxylan
      utilization.
AB  - Environmental and economic factors predicate the need for efficient processing of
      renewable sources of fuels and chemicals. To fulfill this need, microbial
      biocatalysts must be developed to efficiently process the hemicellulose fraction
      of lignocellulosic biomass for fermentation of pentoses. The predominance of
      methylglucuronoxylan (MeGAXn), a beta-1,4 xylan in which 10% to 20% of the xylose
      residues are substituted with alpha-1,2-4-O-methylglucuronate residues, in
      hemicellulose fractions of hardwood and crop residues has made this a target for
      processing and fermentation. A Paenibacillus sp. (strain JDR-2) has been isolated
      and characterized for its ability to efficiently utilize MeGAXn. A modular
      xylanase (XynA1) of glycosyl hydrolase family 10 (GH 10) was identified through
      DNA sequence analysis that consists of a triplicate family 22 carbohydrate
      binding module followed by a GH 10 catalytic domain followed by a single family 9
      carbohydrate binding module and concluding with C-terminal triplicate surface
      layer homology (SLH) domains. Immunodetection of the catalytic domain of XynA1
      (XynA1 CD) indicates that the enzyme is associated with the cell wall fraction,
      supporting an anchoring role for the SLH modules. With MeGAXn as substrate, XynA1
      CD generated xylobiose and aldotetrauronate (MeGAX3) as predominant products. The
      inability to detect depolymerization products in medium during exponential growth
      of Paenibacillus sp. strain JDR-2 on MeGAXn, as well as decreased growth rate and
      yield with XynA1 CD-generated xylooligosaccharides and aldouronates as
      substrates, indicates that XynA1 catalyzes a depolymerization process coupled to
      product assimilation. This depolymerization/assimilation system may be utilized
      for development of biocatalysts to efficiently convert MeGAXn to alternative
      fuels and biobased products.

PMID- 16461705
TI  - In vivo functional assay of a recombinant aquaporin in Pichia pastoris.
AB  - The water channel protein PvTIP3;1 (alpha-TIP) is a member of the major intrinsic
      protein (MIP) membrane channel family. We overexpressed this eukaryotic aquaporin
      in the methylotrophic yeast Pichia pastoris, and immunogold labeling of cellular
      cryosections showed that the protein accumulated in the plasma membrane, as well
      as vacuolar and other intracellular membranes. We then developed an in vivo
      functional assay for water channel activity that measures the change in optical
      absorbance of spheroplasts following an osmotic shock. Spheroplasts of wild-type
      P. pastoris displayed a linear relationship between absorbance and osmotic shock
      level. However, spheroplasts of P. pastoris expressing PvTIP3;1 showed a break in
      this linear relationship corresponding to hypo-osmotically induced lysis. It is
      the difference between control and transformed spheroplasts under conditions of
      hypo-osmotic shock that forms the basis of our aquaporin activity assay. The
      aquaporin inhibitor mercury chloride blocked water channel activity but had no
      effect on wild-type yeast. Osmotically shocked yeast cells were affected only
      slightly by expression of the Escherichia coli glycerol channel GlpF, which
      belongs to the MIP family but is a weak water channel. The important role that
      aquaporins play in human physiology has led to a growing interest in their
      potential as drug targets for treatment of hypertension and congestive heart
      failure, as well as other fluid overload states. The simplicity of this assay
      that is specific for water channel activity should enable rapid screening for
      compounds that modulate water channel activity.

PMID- 16461706
TI  - Use of PMA1 as a housekeeping biomarker for assessment of toxicant-induced stress
      in Saccharomyces cerevisiae.
AB  - The brewer's yeast Saccharomyces cerevisiae has emerged as a versatile and robust
      model system for laboratory use to study toxic effects of various substances. In
      this study, toxicant-induced stresses of pure compounds were investigated in
      Saccharomyces cerevisiae utilizing a destabilized version of the green
      fluorescent protein optimized for expression in yeast (yEGFP3) under control of
      the promoter of the housekeeping plasma membrane ATPase gene PMA1. The responses
      of the biomarker upon increasing test compound concentrations were monitored by
      determining the decrease in fluorescence. The reporter assay deployed a simple
      and robust protocol for the rapid detection of toxic effects within a 96-well
      microplate format. Fluorescence emissions were normalized to cell growth
      determined by absorption and were correlated to internal reference standards. The
      results were expressed as effective concentrations (EC20). Dose-response
      experiments were conducted in which yeast cells were exposed in minimal medium
      and in the presence of 20% fetal calf serum to sublethal concentrations of an
      array of heavy metals, salt, and a number of stress-inducing compounds
      (Diclofenac, Lindane, methyl-N-nitro-N-nitrosoguanidine [MNNG], hydroxyurea, and
      caffeine). Long-term exposure (7 h) played a considerable role in the adaptive
      response to intoxication compared to early responses at 4 h exposure. The data
      obtained after 4 h of exposure and expressed as EC20 were compared to 50%
      inhibitory concentration values derived from cell line and ecotoxicological
      tests. This study demonstrates the versatility of the novel biomarker to
      complement existing test batteries to assess contaminant exposure and effects.

PMID- 16461707
TI  - Colonization of tomato root by pathogenic and nonpathogenic Fusarium oxysporum
      strains inoculated together and separately into the soil.
AB  - In soil, fungal colonization of plant roots has been traditionally studied by
      indirect methods such as microbial isolation that do not enable direct
      observation of infection sites or of interactions between fungal pathogens and
      their antagonists. Confocal laser scanning microscopy was used to visualize the
      colonization of tomato roots in heat-treated soil and to observe the interactions
      between a nonpathogenic strain, Fo47, and a pathogenic strain, Fol8, inoculated
      onto tomato roots in soil. When inoculated separately, both fungi colonized the
      entire root surface, with the exception of the apical zone. When both strains
      were introduced together, they both colonized the root surface and were observed
      at the same locations. When Fo47 was introduced at a higher concentration than
      Fol8, it colonized much of the root surface, but hyphae of Fol8 could still be
      observed at the same location on the root. There was no exclusion of the
      pathogenic strain by the presence of the nonpathogenic strain. These results are
      not consistent with the hypothesis that specific infection sites exist on the
      root for Fusarium oxysporum and instead support the hypothesis that competition
      occurs for nutrients rather than for infection sites.

PMID- 16461708
TI  - Comparative genomics of DNA fragments from six Antarctic marine planktonic
      bacteria.
AB  - Six environmental fosmid clones from Antarctic coastal water bacterioplankton
      were completely sequenced. The genome fragments harbored small-subunit rRNA genes
      that were between 85 and 91% similar to those of their nearest cultivated
      relatives. The six fragments span four phyla, including the Gemmatimonadetes,
      Proteobacteria (alpha and gamma), Bacteroidetes, and high-G+C gram-positive
      bacteria. Gene-finding and annotation analyses identified 244 total open reading
      frames. Amino acid comparisons of 123 and 113 Antarctic bacterial amino acid
      sequences to mesophilic homologs from G+C-specific and SwissProt/UniProt
      databases, respectively, revealed widespread adaptation to the cold. The most
      significant changes in these Antarctic bacterial protein sequences included a
      reduction in salt-bridge-forming residues such as arginine, glutamic acid, and
      aspartic acid, reduced proline contents, and a reduction in stabilizing
      hydrophobic clusters. Stretches of disordered amino acids were significantly
      longer in the Antarctic sequences than in the mesophilic sequences. These
      characteristics were not specific to any one phylum, COG role category, or G+C
      content and imply that underlying genotypic and biochemical adaptations to the
      cold are inherent to life in the permanently subzero Antarctic waters.

PMID- 16461709
TI  - Induction by Klebsiella aerogenes of a melanin-like pigment in Cryptococcus
      neoformans.
AB  - While studying the interaction of Cryptococcus neoformans with Dictyostelium
      discoideum, we noticed that yeast colonies in agar with a feeder lawn of
      Klebsiella aerogenes were brown. This finding was intriguing because C.
      neoformans colonies are not pigmented unless they are provided with precursors
      for melanization. Strains of all C. neoformans serotypes produced brown pigment
      in response to K. aerogenes at 22, 30, and 37 degrees C. Pigment production
      required fungal laccase and was suppressed by high concentrations of glucose.
      Treatment of brown cells with guanidinium isothiocyanate and hot concentrated HCl
      yielded particulate material that had the physical and chemical characteristics
      of melanins. No pigment formation was observed when C. neoformans was exposed to
      live Escherichia coli or heat-killed K. aerogenes. Analysis of K. aerogenes
      supernatants revealed the presence of dopamine, which can be a substrate for
      melanin synthesis by C. neoformans. Our findings illustrate a remarkable
      interaction between a pathogenic fungus and a gram-negative bacterium, in which
      the bacterium produces a substrate that promotes fungal melanization. This
      observation provides a precedent that could explain the source of a substrate for
      C. neoformans melanization in the environment.

PMID- 16461710
TI  - Molecular assays for detecting Aphanomyces invadans in ulcerative mycotic fish
      lesions.
AB  - The pathogenic oomycete Aphanomyces invadans is the primary etiological agent in
      ulcerative mycosis, an ulcerative skin disease caused by a fungus-like agent of
      wild and cultured fish. We developed sensitive PCR and fluorescent peptide
      nucleic acid in situ hybridization (FISH) assays to detect A. invadans.
      Laboratory-challenged killifish (Fundulus heteroclitus) were first tested to
      optimize and validate the assays. Skin ulcers of Atlantic menhaden (Brevoortia
      tyrannus) from populations found in the Pamlico and Neuse River estuaries in
      North Carolina were then surveyed. Results from both assays indicated that all of
      the lesioned menhaden (n = 50) collected in September 2004 were positive for A.
      invadans. Neither the FISH assay nor the PCR assay cross-reacted with other
      closely related oomycetes. These results provided strong evidence that A.
      invadans is the primary oomycete pathogen in ulcerative mycosis and demonstrated
      the utility of the assays. The FISH assay is the first molecular assay to provide
      unambiguous visual confirmation that hyphae in the ulcerated lesions were
      exclusively A. invadans.

PMID- 16461711
TI  - Characterization of metabolism in the Fe(III)-reducing organism Geobacter
      sulfurreducens by constraint-based modeling.
AB  - Geobacter sulfurreducens is a well-studied representative of the Geobacteraceae,
      which play a critical role in organic matter oxidation coupled to Fe(III)
      reduction, bioremediation of groundwater contaminated with organics or metals,
      and electricity production from waste organic matter. In order to investigate G.
      sulfurreducens central metabolism and electron transport, a metabolic model which
      integrated genome-based predictions with available genetic and physiological data
      was developed via the constraint-based modeling approach. Evaluation of the rates
      of proton production and consumption in the extracellular and cytoplasmic
      compartments revealed that energy conservation with extracellular electron
      acceptors, such as Fe(III), was limited relative to that associated with
      intracellular acceptors. This limitation was attributed to lack of cytoplasmic
      proton consumption during reduction of extracellular electron acceptors. Model
      based analysis of the metabolic cost of producing an extracellular electron
      shuttle to promote electron transfer to insoluble Fe(III) oxides demonstrated why
      Geobacter species, which do not produce shuttles, have an energetic advantage
      over shuttle-producing Fe(III) reducers in subsurface environments. In silico
      analysis also revealed that the metabolic network of G. sulfurreducens could
      synthesize amino acids more efficiently than that of Escherichia coli due to the
      presence of a pyruvate-ferredoxin oxidoreductase, which catalyzes synthesis of
      pyruvate from acetate and carbon dioxide in a single step. In silico phenotypic
      analysis of deletion mutants demonstrated the capability of the model to explore
      the flexibility of G. sulfurreducens central metabolism and correctly predict
      mutant phenotypes. These results demonstrate that iterative modeling coupled with
      experimentation can accelerate the understanding of the physiology of poorly
      studied but environmentally relevant organisms and may help optimize their
      practical applications.

PMID- 16461714
TI  - Functional and structural characterization of thermostable D-amino acid
      aminotransferases from Geobacillus spp.
AB  - D-amino acid aminotransferases (D-AATs) from Geobacillus toebii SK1 and
      Geobacillus sp. strain KLS1 were cloned and characterized from a genetic,
      catalytic, and structural aspect. Although the enzymes were highly thermostable,
      their catalytic capability was approximately one-third of that of highly active
      Bacilli enzymes, with respective turnover rates of 47 and 55 s(-1) at 50 degrees
      C. The Geobacillus enzymes were unique and shared limited sequence identities of
      below 45% with D-AATs from mesophilic and thermophilic Bacillus spp., except for
      a hypothetical protein with a 72% identity from the G. kaustophilus genome.
      Structural alignments showed that most key residues were conserved in the
      Geobacillus enzymes, although the conservative residues just before the catalytic
      lysine were distinctively changed: the 140-LRcD-143 sequence in Bacillus D-AATs
      was 144-EYcY-147 in the Geobacillus D-AATs. When the EYcY sequence from the SK1
      enzyme was mutated into LRcD, a 68% increase in catalytic activity was observed,
      while the binding affinity toward alpha-ketoglutarate decreased by half. The
      mutant was very close to the wild-type in thermal stability, indicating that the
      mutations did not disturb the overall structure of the enzyme. Homology modeling
      also suggested that the two tyrosine residues in the EYcY sequence from the
      Geobacillus D-AATs had a pi/pi interaction that was replaceable with the salt
      bridge interaction between the arginine and aspartate residues in the LRcD
      sequence.

PMID- 16461713
TI  - A quorum-quenching approach to investigate the conservation of quorum-sensing
      regulated functions within the Burkholderia cepacia complex.
AB  - Taxonomic studies of the past few years have shown that the Burkholderia cepacia
      complex, a heterogeneous group of B. cepacia-like organisms, consists of at least
      nine species. B. cepacia complex strains are ubiquitously distributed in nature
      and have been used for biocontrol, bioremediation, and plant growth promotion
      purposes. At the same time, B. cepacia complex strains have emerged as important
      opportunistic pathogens of humans, particularly those with cystic fibrosis. All
      B. cepacia complex species investigated thus far use quorum-sensing (QS) systems
      that rely on N-acylhomoserine lactone (AHL) signal molecules to express certain
      functions, including the production of extracellular proteases, swarming
      motility, biofilm formation, and pathogenicity, in a population-density-dependent
      manner. In this study we constructed a broad-host-range plasmid that allowed the
      heterologous expression of the Bacillus sp. strain 240B1 AiiA lactonase, which
      hydrolyzes the lactone ring of various AHL signal molecules, in all described B.
      cepacia complex species. We show that expression of AiiA abolished or greatly
      reduced the accumulation of AHL molecules in the culture supernatants of all
      tested B. cepacia complex strains. Phenotypic characterization of wild-type and
      transgenic strains revealed that protease production, swarming motility, biofilm
      formation, and Caenorhabditis elegans killing efficiency was regulated by AHL in
      the large majority of strains investigated.

PMID- 16461715
TI  - Lack of detrimental effects of Bacillus thuringiensis Cry toxins on the insect
      predator Chrysoperla carnea: a toxicological, histopathological, and biochemical
      analysis.
AB  - The effect of Cry proteins of Bacillus thuringiensis on the green lacewing
      (Chrysoperla carnea) was studied by using a holistic approach which consisted of
      independent, complementary experimental strategies. Tritrophic experiments were
      performed, in which lacewing larvae were fed Helicoverpa armigera larvae reared
      on Cry1Ac, Cry1Ab, or Cry2Ab toxins. In complementary experiments, a
      predetermined amount of purified Cry1Ac was directly fed to lacewing larvae. In
      both experiments no effects on prey utilization or fitness parameters were found.
      Since binding to the midgut is an indispensable step for toxicity of Cry proteins
      to known target insects, we hypothesized that specific binding of the Cry1A
      proteins should be found if the proteins were toxic to the green lacewing. In
      control experiments, Cry1Ac was detected bound to the midgut epithelium of
      intoxicated H. armigera larvae, and cell damage was observed. However, no binding
      or histopathological effects of the toxin were found in tissue sections of
      lacewing larvae. Similarly, Cry1Ab or Cry1Ac bound in a specific manner to brush
      border membrane vesicles from Spodoptera exigua but not to similar fractions from
      green lacewing larvae. The in vivo and in vitro binding results strongly suggest
      that the lacewing larval midgut lacks specific receptors for Cry1Ab or Cry1Ac.
      These results agree with those obtained in bioassays, and we concluded that the
      Cry toxins tested, even at concentrations higher than those expected in real-life
      situations, do not have a detrimental effect on the green lacewing when they are
      ingested either directly or through the prey.

PMID- 16461712
TI  - Multiple-locus sequence typing analysis of Bacillus cereus and Bacillus
      thuringiensis reveals separate clustering and a distinct population structure of
      psychrotrophic strains.
AB  - We used multilocus sequence typing (MLST) to characterize phylogenetic
      relationships for a collection of Bacillus cereus group strains isolated from
      forest soil in the Paris area during a mild winter. This collection contains
      multiple strains isolated from the same soil sample and strains isolated from
      samples from different sites. We characterized 115 strains of this collection and
      19 other strains based on the sequences of the clpC, dinB, gdpD, panC, purF, and
      yhfL loci. The number of alleles ranged from 36 to 53, and a total of 93 allelic
      profiles or sequence types were distinguished. We identified three major strain
      clusters-C, T, and W-based on the comparison of individual gene sequences or
      concatenated sequences. Some less representative clusters and subclusters were
      also distinguished. Analysis of the MLST data using the concept of clonal
      complexes led to the identification of two, five, and three such groups in
      clusters C, T, and W, respectively. Some of the forest isolates were closely
      related to independently isolated psychrotrophic strains. Systematic testing of
      the strains of this collection showed that almost all the strains that were able
      to grow at a low temperature (6 degrees C) belonged to cluster W. Most of these
      strains, including three independently isolated strains, belong to two clonal
      complexes and are therefore very closely related genetically. These clonal
      complexes represent strains corresponding to the previously identified species
      Bacillus weihenstephanensis. Most of the other strains of our collection,
      including some from the W cluster, are not psychrotrophic. B. weihenstephanensis
      (cluster W) strains appear to comprise an effectively sexual population, whereas
      Bacillus thuringiensis (cluster T) and B. cereus (cluster C) have clonal
      population structures.

PMID- 16461716
TI  - Multitiered approach using quantitative PCR to track sources of fecal pollution
      affecting Santa Monica Bay, California.
AB  - The ubiquity of fecal indicator bacteria such as Escherichia coli and
      Enterococcus spp. in urban environments makes tracking of fecal contamination
      extremely challenging. A multitiered approach was used to assess sources of fecal
      pollution in Ballona Creek, an urban watershed that drains to the Santa Monica
      Bay (SMB) near Los Angeles, Calif. A mass-based design at six main-stem sites and
      four major tributaries over a 6-h period was used (i) to assess the flux of
      Enterococcus spp. and E. coli by using culture-based methods (tier 1); (ii) to
      assess levels of Enterococcus spp. by using quantitative PCR and to detect and/or
      quantify additional markers of human fecal contamination, including a human
      specific Bacteroides sp. marker and enterovirus, using quantitative reverse
      transcriptase PCR (tier 2); and (iii) to assess the specific types of enterovirus
      genomes found via sequence analysis (tier 3). Sources of fecal indicator bacteria
      were ubiquitous, and concentrations were high, throughout Ballona Creek, with no
      single tributary dominating fecal inputs. The flux of Enterococcus spp. and E.
      coli averaged 10(9) to 10(10) cells h(-1) and was as high at the head of the
      watershed as at the mouth prior to discharge into the SMB. In addition, a signal
      for the human-specific Bacteroides marker was consistently detected: 86% of the
      samples taken over the extent during the study period tested positive.
      Enteroviruses were quantifiable in 14 of 36 samples (39%), with the highest
      concentrations at the site furthest upstream (Cochran). These results indicated
      the power of using multiple approaches to assess and quantify fecal contamination
      in freshwater conduits to high-use, high-priority recreational swimming areas.

PMID- 16461717
TI  - Temperature-regulated formation of mycelial mat-like biofilms by Legionella
      pneumophila.
AB  - Fifty strains representing 38 species of the genus Legionella were examined for
      biofilm formation on glass, polystyrene, and polypropylene surfaces in static
      cultures at 25 degrees C, 37 degrees C, and 42 degrees C. Strains of Legionella
      pneumophila, the most common causative agent of Legionnaires' disease, were found
      to have the highest ability to form biofilms among the test strains. The
      quantity, rate of formation, and adherence stability of L. pneumophila biofilms
      showed considerable dependence on both temperature and surface material. Glass
      and polystyrene surfaces gave between two- to sevenfold-higher yields of biofilms
      at 37 degrees C or 42 degrees C than at 25 degrees C; conversely, polypropylene
      surface had between 2 to 16 times higher yields at 25 degrees C than at 37
      degrees C or 42 degrees C. On glass surfaces, the biofilms were formed faster but
      attached less stably at 37 degrees C or 42 degrees C than at 25 degrees C. Both
      scanning electron microscopy and confocal laser scanning microscopy revealed that
      biofilms formed at 37 degrees C or 42 degrees C were mycelial mat like and were
      composed of filamentous cells, while at 25 degrees C, cells were rod shaped.
      Planktonic cells outside of biofilms or in shaken liquid cultures were rod
      shaped. Notably, the filamentous cells were found to be multinucleate and lacking
      septa, but a recA null mutant of L. pneumophila was unaffected in its temperature
      regulated filamentation within biofilms. Our data also showed that filamentous
      cells were able to rapidly give rise to a large number of short rods in a fresh
      liquid culture at 37 degrees C. The possibility of this biofilm to represent a
      novel strategy by L. pneumophila to compete for proliferation among the
      environmental microbiota is discussed.

PMID- 16461718
TI  - Dynamic transition of a methanogenic population in response to the concentration
      of volatile fatty acids in a thermophilic anaerobic digester.
AB  - In this study, the microbial community succession in a thermophilic methanogenic
      bioreactor under deteriorative and stable conditions that were induced by
      acidification and neutralization, respectively, was investigated using PCR
      mediated single-strand conformation polymorphism (SSCP) based on the 16S rRNA
      gene, quantitative PCR, and fluorescence in situ hybridization (FISH). The SSCP
      analysis indicated that the archaeal community structure was closely correlated
      with the volatile fatty acid (VFA) concentration, while the bacterial population
      was impacted by pH. The archaeal community consisted mainly of two species of
      hydrogenotrophic methanogen (i.e., a Methanoculleus sp. and a Methanothermobacter
      sp.) and one species of aceticlastic methanogen (i.e., a Methanosarcina sp.). The
      quantitative PCR of the 16S rRNA gene from each methanogen revealed that the
      Methanoculleus sp. predominated among the methanogens during operation under
      stable conditions in the absence of VFAs. Accumulation of VFAs induced a dynamic
      transition of hydrogenotrophic methanogens, and in particular, a drastic change
      (i.e., an approximately 10,000-fold increase) in the amount of the 16S rRNA gene
      from the Methanothermobacter sp. The predominance of the one species of
      hydrogenotrophic methanogen was replaced by that of the other in response to the
      VFA concentration, suggesting that the dissolved hydrogen concentration played a
      decisive role in the predominance. The hydrogenotrophic methanogens existed close
      to bacteria in aggregates, and a transition of the associated bacteria was also
      observed by FISH analyses. The degradation of acetate accumulated during
      operation under deteriorative conditions was concomitant with the selective
      proliferation of the Methanosarcina sp., indicating effective acetate degradation
      by the aceticlastic methanogen. The simple methanogenic population in the
      thermophilic anaerobic digester significantly responded to the environmental
      conditions, especially to the concentration of VFAs.

PMID- 16461719
TI  - Two subpopulations of Listeria monocytogenes occur at subinhibitory
      concentrations of leucocin 4010 and nisin.
AB  - In situ analyses of single Listeria monocytogenes cells at subinhibitory
      concentrations of leucocin 4010 and nisin revealed two subpopulations when
      measured by fluorescence ratio imaging microscopy (FRIM) after staining with 5(6)
      carboxyfluorescein diacetate succinimidyl ester. One subpopulation consisted of
      cells with a dissipated pH gradient (DeltapH), and the other consisted of cells
      that maintained DeltapH. The proportion of cells belonging to each subpopulation
      was estimated, and the concentrations of bacteriocins required to dissipate
      DeltapH for 90% of the cell population (ED90) was predicted. ED90 increased after
      the addition of sodium chloride (1 to 3% [wt/vol]) to the bacteriocin solutions,
      while ED90 decreased by the addition of sodium nitrite (60 and 100 ppm). Other
      meat additives, including sodium phosphate, sodium lactate, sodium citrate, and
      sodium acetate slightly increased ED90. The inhibitory effect of sodium chloride
      on the antilisterial activity of leucocin 4010 and nisin was confirmed on the
      surfaces of meat sausages. This study highlights the important practical
      implications of applying subinhibitory concentrations of bacteriocins, which
      results in unaffected target cells. In situ analyses by FRIM in combination with
      modeling of single-cell data can be applied to ensure that sufficient
      concentrations of bacteriocins are used in food preservation.

PMID- 16461720
TI  - Enhanced benzaldehyde tolerance in Zymomonas mobilis biofilms and the potential
      of biofilm applications in fine-chemical production.
AB  - Biotransformation plays an increasingly important role in the industrial
      production of fine chemicals due to its high product specificity and low energy
      requirement. One challenge in biotransformation is the toxicity of substrates
      and/or products to biocatalytic microorganisms and enzymes. Biofilms are known
      for their enhanced tolerance of hostile environments compared to planktonic free
      living cells. Zymomonas mobilis was used in this study as a model organism to
      examine the potential of surface-associated biofilms for biotransformation of
      chemicals into value-added products. Z. mobilis formed a biofilm with a complex
      three-dimensional architecture comprised of microcolonies with an average
      thickness of 20 microm, interspersed with water channels. Microscopic analysis
      and metabolic activity studies revealed that Z. mobilis biofilm cells were more
      tolerant to the toxic substrate benzaldehyde than planktonic cells were. When
      exposed to 50 mM benzaldehyde for 1 h, biofilm cells exhibited an average of 45%
      residual metabolic activity, while planktonic cells were completely inactivated.
      Three hours of exposure to 30 mM benzaldehyde resulted in sixfold-higher residual
      metabolic activity in biofilm cells than in planktonic cells. Cells inactivated
      by benzaldehyde were evenly distributed throughout the biofilm, indicating that
      the resistance mechanism was different from mass transfer limitation. We also
      found that enhanced tolerance to benzaldehyde was not due to the conversion of
      benzaldehyde into less toxic compounds. In the presence of glucose, Z. mobilis
      biofilms in continuous cultures transformed 10 mM benzaldehyde into benzyl
      alcohol at a steady rate of 8.11 g (g dry weight)(-1) day(-1) with a 90% molar
      yield over a 45-h production period.

PMID- 16461721
TI  - GIP2, a putative transcription factor that regulates the aurofusarin biosynthetic
      gene cluster in Gibberella zeae.
AB  - Gibberella zeae (anamorph: Fusarium graminearum) is an important pathogen of
      maize, wheat, and rice. Colonies of G. zeae produce yellow-to-tan mycelia with
      the white-to-carmine red margins. In this study, we focused on nine putative open
      reading frames (ORFs) closely linked to PKS12 and GIP1, which are required for
      aurofusarin biosynthesis in G. zeae. Among them is an ORF designated GIP2 (for
      Gibberella zeae pigment gene 2), which encodes a putative protein of 398 amino
      acids that carries a Zn(II)2Cys6 binuclear cluster DNA-binding domain commonly
      found in transcription factors of yeasts and filamentous fungi. Targeted gene
      deletion and complementation analyses confirmed that GIP2 is required for
      aurofusarin biosynthesis. Expression of GIP2 in carrot medium correlated with
      aurofusarin production by G. zeae and was restricted to vegetative mycelia.
      Inactivation of the 10 contiguous genes in the DeltaGIP2 strain delineates an
      aurofusarin biosynthetic gene cluster. Overexpression of GIP2 in both the
      DeltaGIP2 and the wild-type strains increases aurofusarin production and reduces
      mycelial growth. Thus, GIP2 is a putative positive regulator of the aurofusarin
      biosynthetic gene cluster, and aurofusarin production is negatively correlated
      with vegetative growth by G. zeae.

PMID- 16461722
TI  - Txp40, a ubiquitous insecticidal toxin protein from Xenorhabdus and Photorhabdus
      bacteria.
AB  - Xenorhabdus and Photorhabdus are gram-negative bacteria that produce a range of
      proteins that are toxic to insects. We recently identified a novel 42-kDa protein
      from Xenorhabdus nematophila that was lethal to the larvae of insects such as
      Galleria mellonella and Helicoverpa armigera when it was injected at doses of 30
      to 40 ng/g larvae. In the present work, the toxin gene txp40 was identified in
      another 59 strains of Xenorhabdus and Photorhabdus, indicating that it is both
      highly conserved and widespread among these bacteria. Recombinant toxin protein
      was shown to be active against a variety of insect species by direct injection
      into the larvae of the lepidopteran species G. mellonella, H. armigera, and
      Plodia interpunctella and the dipteran species Lucilia cuprina. The protein
      exhibited significant cytotoxicity against two dipteran cell lines and two
      lepidopteran cell lines but not against a mammalian cell line. Histological data
      from H. armigera larvae into which the toxin was injected suggested that the
      primary site of action of the toxin is the midgut, although some damage to the
      fat body was also observed.

PMID- 16461723
TI  - Biodiversity of methanogenic and other archaea in the permanently frozen Lake
      Fryxell, Antarctica.
AB  - Archaea were detected in molecular diversity studies of the permanently frozen
      Lake Fryxell, Antarctica. Two clusters of methanogens were detected in the
      sediments, and another cluster of possibly methanotrophic Euryarchaeota was
      detected in the anoxic water column just above the sediments. One crenarchaeote
      was detected in water just below the oxycline. The Archaea present in Lake
      Fryxell are likely involved in the major biogeochemical cycles that occur there.

PMID- 16461724
TI  - Analysis of expressed sequence tag data and gene expression profiles involved in
      conidial germination of Fusarium oxysporum.
AB  - We obtained 3,372 tentative unique transcripts (TUTs) from a cDNA library of
      Fusarium oxysporum. A cDNA array with 3,158 TUTs was produced to analyze gene
      expression profiles in conidial germination. It seems that ras and other
      signaling genes, e.g., ccg, cooperatively initiate conidial germination in
      Fusarium by increasing protein synthesis.

PMID- 16461725
TI  - mRNA-based parallel detection of active methanotroph populations by use of a
      diagnostic microarray.
AB  - A method was developed for the mRNA-based application of microbial diagnostic
      microarrays to detect active microbial populations. DNA- and mRNA-based analyses
      of environmental samples were compared and confirmed via quantitative PCR.
      Results indicated that mRNA-based microarray analyses may provide additional
      information on the composition and functioning of microbial communities.

PMID- 16461726
TI  - A Bacillus megaterium plasmid system for the production, export, and one-step
      purification of affinity-tagged heterologous levansucrase from growth medium.
AB  - A multiple vector system for the production and export of recombinant affinity
      tagged proteins in Bacillus megaterium was developed. Up to 1 mg/liter of a His6
      tagged or Strep-tagged Lactobacillus reuteri levansucrase was directed into the
      growth medium, using the B. megaterium esterase LipA signal peptide, and
      recovered by one-step affinity chromatography.

PMID- 16461727
TI  - Characterization of bacterial communities associated with deep-sea corals on Gulf
      of Alaska seamounts.
AB  - Although microbes associated with shallow-water corals have been reported,
      deepwater coral microbes are poorly characterized. A cultivation-independent
      analysis of Alaskan seamount octocoral microflora showed that Proteobacteria
      (classes Alphaproteobacteria and Gammaproteobacteria), Firmicutes, Bacteroidetes,
      and Acidobacteria dominate and vary in abundance. More sampling is needed to
      understand the basis and significance of this variation.

PMID- 16461728
TI  - Cumulative effects of short-term polymetal contamination on soil bacterial
      community structure.
AB  - In this study we evaluated the short-term effects of copper, cadmium, and
      mercury, added singly or in combination at different doses, on soil bacterial
      community structure using the bacterial automated ribosomal intergenic spacer
      analysis (B-ARISA) fingerprinting technique. Principal-component analysis of B
      ARISA profiles allowed us to deduce the following order of impact: (Cu + Cd + Hg)
      >> Hg > or = Cd > Cu. These results demonstrated that there was a cumulative
      effect of metal toxicity. Furthermore, the trend of modifications was consistent
      with the "hump-backed" relationships between biological diversity and disturbance
      described by Giller et al. (K. E. Giller, E. Witler, and S. P. McGrath, Soil
      Biol. Biochem. 30:1389-1414, 1998).

PMID- 16461729
TI  - Improvement of oligonucleotide probe design criteria for functional gene
      microarrays in environmental applications.
AB  - To optimize oligonucleotide probe design criteria, PCR products with different
      similarities to probes were hybridized to a functional gene microarray designed
      to detect homologous genes from different organisms. In contrast to more
      restrictive probe designs based on a single criterion, simultaneous consideration
      of the percent similarity (< or =90%), the length of identical sequence stretches
      (< or =20 bases), and the binding free energy (> or =-35 kcal mol(-1)) was found
      to be predictive of probe specificity.

PMID- 16461730
TI  - Measurement of respiration rates of Methylobacterium extorquens AM1 cultures by
      use of a phosphorescence-based sensor.
AB  - Respiration rates of bacterial cultures can be a powerful tool in gauging the
      effects of genetic manipulation and environmental changes affecting overall
      metabolism. We present an optical method for measuring respiration rates using a
      robust phosphorescence lifetime-based sensor and off-the-shelf technology. This
      method was tested with the facultative methylotroph Methylobacterium extorquens
      AM1 to demonstrate subtle mutant phenotypes.

PMID- 16461731
TI  - Probing in vivo promoter activities in Mycoplasma pneumoniae: a system for
      generation of single-copy reporter constructs.
AB  - The nucleotide sequences that control transcription initiation and regulation in
      Mycoplasma pneumoniae are poorly understood. In this work, we developed a lacZ
      based reporter plasmid that can be used to integrate fusions of promoter
      fragments to a promoterless lacZ gene into the chromosome of M. pneumoniae.

PMID- 16461732
TI  - Caenorhabditis elegans is a model host for Listeria monocytogenes.
AB  - Here we report that Caenorhabditis elegans nematodes fed Listeria monocytogenes
      die over the course of several days, as a consequence of an accumulation of
      bacteria in the worm intestine. Mutant strains previously shown to be important
      for virulence in mammalian models were also found to be attenuated in their
      virulence in C. elegans. However, ActA, which is required for actin-based
      intracellular motility, appears to be dispensable during infection of C. elegans,
      indicating that L. monocytogenes remains extracellular in C. elegans.

PMID- 16461733
TI  - Freezing induces biased results in the molecular detection of Flavobacterium
      columnare.
AB  - Specific PCR detection and electron microscopy of Flavobacterium columnare
      revealed the risk of false-negative results in molecular detection of this fish
      pathogen. Freezing and thawing destroyed the cells so that DNA was for the most
      part undetectable by PCR. The detection of bacteria was also weakened after
      prolonged enrichment cultivation of samples from infected fish.

PMID- 16461734
TI  - Isolation of Rickettsia felis in the mosquito cell line C6/36.
AB  - We report the isolation and establishment of Rickettsia felis in the C6/36 cell
      line. Rickettsial growth was intense, always with 90 to 100% of cells being
      infected after few weeks. The rickettsial isolate was confirmed by testing
      infected cells by PCR and sequencing fragments of three major Rickettsia genes
      (gltA, ompB, and the 17-kDa protein gene).

PMID- 16461736
TI  - Differential expression of leukocyte-associated Ig-like receptor-1 during
      neutrophil differentiation and activation.
AB  - Inhibitory receptors containing immunoreceptor tyrosine-based inhibitory motifs
      play an important regulatory role in immune cell activation. In addition, several
      studies suggest that these receptors are involved in the regulation of
      hematopoietic cell differentiation. Here, we have investigated the expression of
      leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), an inhibitory
      receptor expressed on most peripheral blood leukocytes and on CD34+ hematopoietic
      progenitor cells, in neutrophil differentiation and activation. We found that
      although LAIR-1 was expressed on peripheral blood eosinophils, cell-surface
      expression on mature neutrophils was low, suggesting that LAIR-1 expression is
      regulated during granulocyte differentiation. Indeed, the promyeloid cell line HL
      60 expressed LAIR-1, but the expression decreased during chemical-induced
      differentiation toward neutrophils. Similarly, in bone marrow-derived neutrophil
      precursors, the most immature cells expressed LAIR-1, and loss of LAIR-1
      expression was associated with neutrophil maturation. LAIR-1 was re-expressed
      rapidly on the membrane of mature neutrophils upon stimulation with tumor
      necrosis factor alpha, granulocyte macrophage-colony stimulating factor, or N
      formyl-methionyl-leucyl-phenylalanine, indicating that LAIR-1 may also regulate
      neutrophil effector function. Our studies suggest that LAIR-1 may play a
      regulatory role in differentiation and function of human granulocytes.

PMID- 16461735
TI  - Diversity of microorganisms within rock varnish in the Whipple Mountains,
      California.
AB  - Rock varnish from Arizona's Whipple Mountains harbors a microbial community
      containing about 10(8) microorganisms g(-1) of varnish. Analyses of varnish
      phospholipid fatty acids and rRNA gene libraries reveal a community comprised of
      mostly Proteobacteria but also including Actinobacteria, eukaryota, and a few
      members of the Archaea. Rock varnish represents a significant niche for microbial
      colonization.

PMID- 16461737
TI  - Chemokine- and adhesion-dependent survival of neutrophils after transmigration
      through cytokine-stimulated endothelium.
AB  - We examined the fate of neutrophils following transmigration through an
      endothelial monolayer cultured on "Transwell" membrane filters. Treatment of
      human umbilical vein endothelial cells (HUVEC) with increasing doses of tumor
      necrosis factor-alpha increased the efficiency of transmigration and markedly
      reduced apoptosis among the transmigrated neutrophils in a dose-dependent manner.
      Apoptosis was also inhibited after transmigration of neutrophils through HUVEC
      stimulated with interleukin (IL)-1beta but not so effectively after chemotaxis
      through unstimulated HUVEC driven by IL-8 added below the filter. Inhibition of
      beta2-integrin binding after transmigration or coating the lower chamber with a
      nonadhesive polymer (polyhydroxyl-ethyl-methacrylate) abrogated neutrophil
      survival. Although integrin engagement during migration itself was not essential
      to inhibit apoptosis, activation of neutrophils through CXC chemokine receptors
      was necessary. Quite brief exposure to the HUVEC (30-120 min) was effective in
      reducing subsequent apoptosis, although if coincubation with the HUVEC were
      prolonged, neutrophil apoptosis was reduced further. Neutralization of
      granulocyte macrophage-colony stimulating factor inhibited this additional
      effect. Thus, a complex interplay between migration- and activation-dependent
      signals and adhesive interaction in tissue may combine to effectively prolong the
      survival of neutrophils recruited during inflammation.

PMID- 16461738
TI  - DC-SIGN (CD209) recognition of Neisseria gonorrhoeae is circumvented by
      lipooligosaccharide variation.
AB  - Neisseria gonorrhoeae (GC) or Escherichia coli HB101 (hereafter referred to as E.
      coli) expressing opacity (Opa) proteins adhere to human host cells and stimulate
      phagocytosis as a result of the interaction of certain Opa proteins to
      carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1; CD66a)
      receptors. Our experiments show that the Opa-CEACAM1 interaction does not play a
      significant role in adherence between these bacteria and dendritic cells (DCs).
      Instead, phagocytosis of GC and E. coli by DCs is mediated by the DC-specific
      intercellular adhesion molecule-grabbing nonintegrin, (SIGN; CD209) receptor. DC
      SIGN recognition and subsequent phagocytosis of GC are limited, however, to a
      lipooligosaccharide (LOS) mutant (lgtB) of GC. This conclusion is supported by
      experiments demonstrating that HeLa cells expressing human DC-SIGN (HeLa-DC-SIGN)
      bind exclusively to and engulf an lgtB mutant of GC, and this interaction is
      blocked specifically by an anti-DC-SIGN antibody. The experiments suggest that
      LOS variation may have evolved as a mechanism for GC to avoid phagocytosis by
      DCs.

PMID- 16461739
TI  - Sex-specific phenotypical and functional differences in peripheral human
      Vgamma9/Vdelta2 T cells.
AB  - Vgamma9/Vdelta2 T cells constitute a minor proportion of human peripheral blood T
      cells that can expand rapidly upon infection with microbial pathogens.
      Vgamma9/Vdelta2 T cell numbers change characteristically with age, rising from
      birth to puberty and gradually decreasing again beyond 30 years of age. In
      adults, female blood donors have significantly higher levels than males, implying
      that circulating Vgamma9/Vdelta2 T cells in women remain elevated for a longer
      period in life and drop less strikingly than in men. This loss in men is
      accompanied by a substantial depletion of CD27- CD45RA- and CD27- CD45RA+
      effector T cells and a parallel increase in CD27+ CD45RA- central memory T cells
      while in women, the distribution of Vgamma9/Vdelta2 T cell subsets remains
      virtually unchanged. The phenotypical conversion in men older than 30 years is
      mirrored by an increased proliferative response of Vgamma9/Vdelta2 T cells and a
      reduced interferon-gamma secretion upon stimulation with isopentenyl
      pyrophosphate in vitro.

PMID- 16461740
TI  - L-selectin and intercellular adhesion molecule-1 regulate the development of
      Concanavalin A-induced liver injury.
AB  - Concanavalin A (Con A)-induced hepatitis is a model for human T cell-mediated
      hepatitis. We evaluated the role of L-selectin and intercellular adhesion
      molecule-1 (ICAM-1) in this model by injecting Con A intravenously in mice
      lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/-), or both (L-selectin/ICAM
      1-/-). Blood and liver samples were collected 0, 8, 24, and 48 h after Con A
      treatment. Increases in plasma transaminase levels, which peaked 8 h after
      injection, were reduced significantly in L-selectin-/-, ICAM-1-/-, and L
      selectin/ICAM-1-/- mice compared with wild-type mice. Liver necrosis was more
      strongly inhibited in ICAM-1-/- mice than in L-selectin-/- mice but was most
      prominently reduced in L-selectin/ICAM-1-/- mice, in parallel with decreased
      plasma transaminase levels. The reduced severity of hepatitis in the mutant mice
      correlated with decreases in numbers of liver CD4+ T cells but not numbers of
      CD8+ T cells or neutrophils. Following Con A treatment, L-selectin deficiency
      reduced liver mRNA expression of tumor necrosis factor-alpha, and ICAM-1
      deficiency reduced expression of interleukin-4. By contrast, reductions in liver
      macrophage inhibitor protein-1alpha mRNA occurred in all mutant mice. These
      results indicate that L-selectin and ICAM-1 contribute cooperatively to the
      development of Con A-induced hepatitis by regulating leukocyte infiltration and
      subsequent cytokine production.

PMID- 16461741
TI  - Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are
      associated with reduced IRAK-1 expression and MyD88-IRAK complex formation.
AB  - Tolerance to bacterial cell-wall components may represent an essential regulatory
      mechanism during bacterial infection. We have demonstrated previously that the
      inhibition of nuclear factor (NF)-kappaB and mitogen-activated protein kinase
      activation was present in bacterial lipoprotein (BLP) self-tolerance and its
      cross-tolerance to lipopolysaccharide (LPS). In this study, the effect of BLP
      induced tolerance on the myeloid differentiation factor 88 (MyD88)-dependent
      upstream signaling pathway for NF-kappaB activation in vitro was examined
      further. When compared with nontolerant human monocytic THP-1 cells, BLP-tolerant
      cells had a significant reduction in tumor necrosis factor alpha (TNF-alpha)
      production in response to a high-dose BLP (86+/-12 vs. 6042+/-245 ng/ml, P <
      0.01) or LPS (341+/-36 vs. 7882+/-318 ng/ml, P < 0.01) stimulation. The
      expression of Toll-like receptor 2 (TLR2) protein was down-regulated in BLP
      tolerant cells, whereas no significant differences in TLR4, MyD88, interleukin-1
      receptor-associated kinase 4 (IRAK-4), and TNF receptor-associated factor 6
      expression were observed between nontolerant and BLP-tolerant cells, as confirmed
      by Western blot analysis. The IRAK-1 protein was reduced markedly in BLP-tolerant
      cells, although IRAK-1 mRNA expression remained unchanged as revealed by real
      time reverse transcriptase-polymerase chain reaction analysis. Furthermore,
      decreased MyD88-IRAK immunocomplex formation, as demonstrated by
      immunoprecipitation, was observed in BLP-tolerant cells following a second BLP or
      LPS stimulation. BLP pretreatment also resulted in a marked inhibition in total
      and phosphorylated inhibitor of kappaB-alpha (IkappaB-alpha) expression, which
      was not up-regulated by subsequent BLP or LPS stimulation. These results
      demonstrate that in addition to the down-regulation of TLR2 expression, BLP
      tolerance is associated with a reduction in IRAK-1 expression, MyD88-IRAK
      association, and IkappaB-alpha phosphorylation. These findings further elucidate
      the molecular mechanisms underlying bacterial peptide tolerance.

PMID- 16461742
TI  - Regulation of PTX3, a key component of humoral innate immunity in human dendritic
      cells: stimulation by IL-10 and inhibition by IFN-gamma.
AB  - The protopypic long pentraxin 3 (PTX3) is a unique, humoral pattern-recognition
      receptor, which plays a nonredundant function in innate resistance to pathogens.
      Dendritic cells (DC) of myelomonocytic origin, but not plasmacytoid DC, are a
      major source of PTX3 in response to Toll-like receptor (TLR) engagement. The
      present study was designed to explore the regulation of PTX3 production in DC.
      PTX3 production was induced by TLR ligands, CD40 ligand, and interleukin (IL)
      1beta and was suppressed by dexamethasone, 1alpha, 25-dihydroxivitamin D3, and
      prostaglandin E2. It was unexpected that lipopolysaccharide (LPS)-stimulated PTX3
      production was enhanced by IL-10 and inhibited by IL-4 and interferon-gamma (IFN
      gamma). Enhancement of PTX3 production by IL-10 was also evident when Pam3 Cys
      Ser-(Lys)4.3HCl, a TLR2-TLR1 agonist, polyionisicpolycytidylic acid, a TLR3
      agonist, and IL-1beta were used as stimuli. The effect of IL-10 was blocked by an
      anti-IL-10 monoclonal antibody (mAb) or an anti-IL-10 receptor alpha mAb, which
      also reduced the LPS-induced production. Thus, production of PTX3 in DC is
      subjected to a distinct regulatory network, with inhibition by IFN-gamma and
      enhancement by IL-10. The amplification by IL-10 of production of a nonredundant
      component of fluid-phase innate immunity mirrors the IL-10 stimulatory function
      on B cells in adaptive immunity. As PTX3 is also an extracellular matrix
      component, IL-10-enhanced PTX3 production may play a role in orchestration of
      tissue remodeling in chronic inflammation.

PMID- 16461743
TI  - Impaired dendritic cell function in Crohn's disease patients with NOD2 3020insC
      mutation.
AB  - The nucleotide oligomerization domain 2 (NOD2) 3020insC (NOD2fs) mutation
      increases susceptibility to Crohn's disease (CD), but the mechanism remains
      controversial. Loss-of-function and gain-of-function phenotypes have been
      described as a result of NOD2fs. Here, we show that dendritic cells (DC) derived
      from CD patients homozygous for this mutation respond normally to purified Toll
      like receptor (TLR) ligands but fail to up-regulate the costimulatory molecules
      CD80 and CD86 in response to the NOD2 ligand muramyl dipeptide (MDP). Moreover,
      they lack MDP-induced enhancement of TLR-mediated tumor necrosis factor alpha,
      interleukin (IL)-12, and IL-10 production, which is observed in control DC with
      intact NOD2. These data indicate that the NOD2fs mutation results in a loss-of
      function phenotype in human myeloid DC and imply decreased immune regulation by
      IL-10 as a possible mechanism for this mutation in CD.

PMID- 16461744
TI  - Divergent expression and function of glucocorticoid receptor beta in human
      monocytes and T cells.
AB  - Glucocorticoid (GC) insensitivity is a significant problem in the treatment of
      immune-mediated diseases. The current study examined whether T cells and
      monocytes differed in their response to GC and the potential molecular basis for
      their variation in response to steroids. Functional studies revealed that
      dexamethasone (DEX) inhibited phorbol 12-myristate 13-acetate/ionomycin-induced
      tumor necrosis factor alpha and interleukin-6 production to a significantly
      lesser extent in monocytes than T cells. In parallel, a significantly longer
      period of time was required for DEX to induce the steroid-responsive gene,
      mitogen-activated protein kinase phosphatase-1 (MKP-1), in human monocytes as
      compared with T cells. It is interesting that such differences were not observed
      between murine T cells and monocytes. GC receptor beta (GCRbeta) is a splicing
      variant of the classic GCR, GCRalpha, which functions as a dominant-negative
      inhibitor of GCRalpha in humans, not mice (as mice do not express GCRbeta mRNA as
      a result of a difference in the murine GCR 9b exon sequence). It was found that
      human monocytes had a significantly higher level of GCRbeta than T cells.
      Furthermore, GCRbeta was found in the cytoplasm and nucleus of monocytes, and
      GCRbeta was localized to the nucleus of T cells. This raised the possibility that
      GCRbeta in the cytoplasm could affect GCRalpha cellular shuttling in response to
      DEX. Indeed, we found that DEX-induced nuclear translocation of GCRalpha was
      decreased in monocytes as compared with T cells. Specific RNA silencing of
      GCRbeta in human monocytes resulted in enhanced steroid-induced GCRalpha
      transactivation and transrepression. Our data suggest that GCRbeta contributes to
      variation in the GC responses of monocytes versus T cells.

PMID- 16461745
TI  - High-level expression of B7-H1 molecules by dendritic cells suppresses the
      function of activated T cells and desensitizes allergen-primed animals.
AB  - A body of evidence indicates that expression of the programmed cell death 1 (PD
      1) receptor by activated T cells plays an important role in the down-regulation
      of immune responses; however, the functions of its known ligands, B7-H1 (PD-L1)
      and B7-dendritic cell (DC; PD-L2), at the effector phase of immune responses are
      less clear. In the current study, we investigated the roles of B7-H1 in DC
      mediated regulation of hapten-activated T cells and the delayed-type contact
      hypersensitivity response in primed animals. We found that the expression of B7
      H1 and B7-DC was induced on activation of DC by hapten stimulation. Blockade of
      B7-H1, but not B7-DC, enhanced the activity of hapten-specific T cells.
      Interaction with a DC line that expresses high cell-surface levels of B7-H1 (B7
      H1/DC) suppressed the proliferation of, and cytokine production by, activated T
      cells. In vivo administration of hapten-carrying B7-H1/DC desensitized the
      response of sensitized animals to hapten challenge, and this desensitization was
      hapten-specific. These data indicate that B7-H1 expressed by DC mediates
      inhibitory signals for activated T cells and suppresses the elicitation of immune
      responses. The ability of B7-H1/DC to inhibit the function of preactivated T
      cells in vivo suggests novel strategies for the treatment of immune response
      mediated disorders.

PMID- 16461746
TI  - Imatinib mesylate minimally affects bcr-abl+ and normal monocyte-derived
      dendritic cells but strongly inhibits T cell expansion despite reciprocal
      dendritic cell-T cell activation.
AB  - In chronic myeloid leukemia, bcr-abl+ monocytes provide a unique opportunity to
      generate dendritic cells (DC) expressing a broad spectrum of leukemic antigens,
      and bcr-abl+ DC vaccines may allow immunological eradication of leukemic cells
      persisting under treatment with the tyrosine kinase inhibitor imatinib. However,
      the efficiency of bcr-abl+ DC vaccines will critically depend on the absence of
      deleterious effects of bcr-abl and of imatinib on DC functions. We show that bcr
      abl+ monocytes, devoid of contamination of CD14low granulocytic precursors,
      differentiate into DC with typical immunophenotypical and functional features,
      and bcr-abl transcription decreases simultaneously. During differentiation,
      imatinib induces a slight increase of DC apoptosis and prevents CD1a up
      regulation in a dose-dependent manner in bcr-abl+ and normal monocyte-derived DC,
      but at most, 25% of DC fail to acquire CD1a. When DC maturation is induced in the
      presence of imatinib, bcr-abl+ and normal monocyte-derived DC up-regulate major
      histocompatibility complex and costimulatory molecules, CC chemokine receptor 7
      and CD83. However, secretion of interleukin-12p70 is decreased in a dose
      dependent manner. Imatinib exposure of bcr-abl+ and normal monocyte-derived DC
      during differentiation and maturation is not detrimental to T cell
      immunostimulatory functions of DC. In sharp contrast, imatinib, when added to DC
      T cell cultures, profoundly suppresses DC-mediated T cell proliferation, despite
      reciprocal DC-T cell activation attested by up-regulation of CD25 on T cells and
      of CD86 on DC. Our findings demonstrate that T cells, not normal or bcr-abl+
      monocyte-derived DC, are major targets for imatinib immunomodulatory effects. It
      can be envisioned already that imatinib-free windows will be required to enable
      vaccination-induced, leukemia-specific T cell expansion.

PMID- 16461747
TI  - p53 regulates Btk-dependent B cell proliferation but not differentiation.
AB  - Btk is critical for B cell development and proliferation. Mice lacking Btk have a
      defect in B cell development, resulting in a loss of mature B cells and decreased
      proliferative responses following B cell receptor cross-linking. In contrast,
      mice deficient in the tumor suppressor p53 display increases in developing B cell
      populations in the bone marrow. To investigate the potential role of p53 in Btk
      dependent B cell development and function, we generated mice doubly-deficient in
      p53 and Btk. Btk/p53-deficient mice showed an increase in splenic B220+ cell
      numbers compared with Btk-deficient mice, although there was no recovery in B
      cell subset differentiation. In contrast to the lack of recovery of B cell
      development, there was a recovery in lipopolysaccharide and anti-immunoglobulin M
      (IgM) plus interleukin-4-induced proliferation of Btk/p53-deficient B cells,
      although there was no recovery to anti-IgM stimulation alone. Thus, p53 promotes
      B cell expansion and proliferation, but p53 deficiency cannot compensate for Btk
      deficiency in the development of B cell subsets.

PMID- 16461748
TI  - 24-hour pretreatment with delta opioid enhances survival from hemorrhagic shock.
AB  - OBJECTIVES: Delta opioids have been shown to confer ischemic preconditioning and
      pharmacologic ischemic preconditioning to the myocardium. However, their role in
      providing extended pharmacologic ischemic preconditioning in hemorrhagic shock
      has not been explored. The authors examined the effects of 24-hour preinfusions
      of a selective delta opioid receptor agonist, Deltorphin-Dvariant (Delt-Dvar), on
      hemodynamic stability and duration of survival in a rat model of severe
      hemorrhagic shock. METHODS: Conscious Sprague-Dawley rats with indwelling
      catheters were hemorrhaged at a rate of 3.18 mL/l00 g over 20 minutes. Twenty
      four hours before hemorrhage, the control group (n = 14) was infused with 1.0 mL
      lactated Ringer's solution, and the Delt-Dvar-treated group (n = 22) was infused
      with 5.0 mg/kg Delt-Dvar in 1.0 mL lactated Ringer's solution. Rats were
      continuously monitored for heart rate (HR), mean arterial pressure, and four-hour
      survival rates. Plasma lactate levels were determined at the beginning of
      hemorrhage and the end of hemorrhage. RESULTS: At 240 minutes, only one of 14
      controls (7.1%) survived, while 16 (72.7%) of the 22 experimental rats survived.
      No significant differences in heart rate between controls and Delt-Dvar-treated
      rats were noted. Increases in mean arterial pressure of Delt-Dvar-treated rats at
      the beginning of hemorrhage and at the end of hemorrhage were found to be
      significant (p < 0.05). At 240 minutes, heart rate and mean arterial pressure
      were not different between the single surviving control and the Delt-Dvar group.
      At the end of hemorrhage, lactate levels in the Delt-Dvar-treated group were 8.5
      (+/- 0.5) mmol/L versus 10.8 (+/- 0.6) mmol/L (p < 0.05) in the control group.
      CONCLUSIONS: Twenty-four-hour pretreatment with Delt-Dvar decreases plasma
      lactate levels and improves hemodynamic stability and survival during hemorrhagic
      shock. The use of delta-specific opioids may improve survival from hemorrhagic
      shock and have clinical utility in providing ischemic protection in scenarios of
      planned ischemia.

PMID- 16461753
TI  - Human patients or simulators for teaching endotracheal intubation: whom are we
      fooling?

PMID- 16461754
TI  - Sound levels in the emergency department setting.

PMID- 16461755
TI  - Products of heme oxygenase and their potential therapeutic applications.
AB  - Heme oxygenase 1 (HO-1) is induced in response to cellular stress and is
      responsible for converting the prooxidant heme molecule into equimolar quantities
      of biliverdin (BV), carbon monoxide (CO), and iron. BV is then converted to
      bilirubin (BR) by the enzyme biliverdin reductase. Experimental evidence suggests
      that induction of the HO system is an important endogenous mechanism for
      cytoprotection and that the downstream products of heme degradation, CO, BR, and
      BV, may mediate these powerful beneficial effects. These molecules, which were
      once considered to be toxic metabolic waste products, have recently been shown to
      have dose-dependent vasodilatory, antioxidant, and anti-inflammatory properties
      that are particularly desirable for tissue protection during organ
      transplantation. In fact, recent work has demonstrated that administration of
      exogenous CO, BR, or BV may offer a simple, inexpensive method to substitute for
      the cytoprotective effects of HO-1 in a variety of clinically applicable models.
      This review will attempt to summarize the relevant biochemical and cytoprotective
      properties of CO, BR, and BV, and will discuss emerging studies involving the
      therapeutic applications of these molecules in the kidney and other organ
      systems.

PMID- 16461756
TI  - Claudins at the gate: determinants of renal epithelial tight junction
      paracellular permeability.
AB  - The epithelial tight junction (TJ) is responsible for the control of paracellular
      transport between epithelial cells (gate function) and the maintenance of
      apical/basolateral polarity by preventing the diffusion of membrane lipids and/or
      proteins from one surface domain to another (fence function). Renal tubule
      epithelia in the mammalian nephron have TJs that determine paracellular transport
      characteristics. Paracellular transport across renal tubular epithelial TJs (gate
      function) varies in different segments of the nephron. A large family of recently
      identified TJ-associated transmembrane proteins named claudins appear to
      determine the paracellular permeability properties of the TJ. A combination of
      inherited human diseases, renal epithelial cell culture models, and nephron
      expression patterns of claudins is providing important clues about how claudin
      molecules determine the TJ gate function of renal epithelia in different segments
      of the nephron.

PMID- 16461757
TI  - SLC4 base (HCO3 -, CO3 2-) transporters: classification, function, structure,
      genetic diseases, and knockout models.
AB  - In prokaryotic and eukaryotic organisms, biochemical and physiological processes
      are sensitive to changes in H(+) activity. For these processes to function
      optimally, a variety of proteins have evolved that transport H(+)/base
      equivalents across cell and organelle membranes, thereby maintaining the pH of
      various intracellular and extracellular compartments within specific limits. The
      SLC4 family of base (HCO(3)(-), CO(3)(2(-))) transport proteins plays an
      essential role in mediating Na(+)- and/or Cl(-)-dependent base transport in
      various tissues and cell types in mammals. In addition to pH regulation, specific
      members of this family also contribute to vectorial transepithelial base
      transport in several organ systems including the kidney, pancreas, and eye. The
      importance of these transporters in mammalian cell biology is highlighted by the
      phenotypic abnormalities resulting from spontaneous SLC4 mutations in humans and
      targeted deletions in murine knockout models. This review focuses on recent
      advances in our understanding of the molecular organization and functional
      properties of SLC4 transporters and their role in disease.

PMID- 16461758
TI  - Membrane trafficking and the regulation of NKCC2.

PMID- 16461759
TI  - WNK signaling in the distal tubule: an inhibitory cascade regulating salt
      transport.

PMID- 16461760
TI  - Cholesterol substrate pools and steroid hormone levels are normal in the face of
      mutational inactivation of NPC1 protein.
AB  - Mutational inactivation of NPC1 largely blocks the movement of LDL-derived
      cholesterol from the lysosome to the metabolically active, cytosolic pool of
      sterol that is the substrate for steroid hormone production. Such a block might,
      in theory, lead to deficiencies in circulating levels of testosterone,
      progesterone, and corticosterone. However, there are at least two other sources
      for cellular cholesterol, de novo synthesis and scavenger receptor class B type I
      mediated uptake of HDL cholesteryl ester (CE). In this study, we measured the
      rates of net cholesterol acquisition by these three pathways in the adrenal,
      ovary, and testis. In all three organs, the majority (81-98%) of cholesterol
      acquisition came from the selective uptake of CE from HDL and de novo synthesis.
      Furthermore, in the npc1(-/-)mouse, the cytosolic storage pool of CE in a tissue
      such as the adrenal remained constant (approximately 25 mg/g). As a result of
      these alternative pathways, the plasma concentrations of testosterone (3.5 vs.
      2.5 ng/ml), progesterone (8.5 vs. 6.7 ng/ml), and corticosterone (391 vs. 134
      ng/ml) were either the same or elevated in the npc1(-/-)mouse, compared with the
      control animal. Thus, impairment of cholesterol acquisition through the NPC1
      dependent, clathrin-coated pit pathway did not limit the availability of
      cholesterol substrate for steroid hormone synthesis in the steroidogenic cells.

PMID- 16461761
TI  - Marburg I polymorphism of factor VII-activating protease and risk of venous
      thromboembolism.

PMID- 16461762
TI  - Experience with bortezomib for the treatment of patients with relapsed classical
      Hodgkin lymphoma.

PMID- 16461763
TI  - Long-term engraftment and clonal dominance of donor-derived del(20q)
      hematopoietic cells after allogeneic stem cell transplantation.

PMID- 16461764
TI  - More on Myb in myelofibrosis: molecular analyses of MYB and EP300 in 55 patients
      with myeloproliferative disorders.

PMID- 16461765
TI  - Screening and counseling for thalassemia.

PMID- 16461766
TI  - Protein S-K196E mutation as a genetic risk factor for deep vein thrombosis in
      Japanese patients.

PMID- 16461767
TI  - Integrin alpha2-mediated ERK and calpain activation play a critical role in cell
      adhesion and motility via focal adhesion kinase signaling: identification of a
      novel signaling pathway.
AB  - Higher levels of focal adhesion kinase (FAK) are expressed in colon metastatic
      carcinomas. However, the signaling pathways and their mechanisms that control
      cell adhesion and motility, important components of cancer metastasis, are not
      well understood. We sought to identify the integrin-mediated mechanism of FAK
      cleavage and downstream signaling as well as its role in motility in human colon
      cancer GEO cells. Our results demonstrate that phosphorylated FAK (tyrosine 397)
      is cleaved at distinct sites by integrin signaling when cells attach to collagen
      IV. Specific blocking antibodies (clone P1E6) to integrin alpha2 inhibited FAK
      activation and cell motility (micromotion). Ectopic expression of the FAK C
      terminal domain FRNK attenuated FAK and ERK phosphorylation and micromotion.
      Calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal blocked FAK cleavage, cell
      adhesion, and micromotion. Antisense approaches established an important role for
      mu-calpain in cell motility. Expression of wild type mu-calpain increased cell
      micromotion, whereas its point mutant reversed the effect. Further, cytochalasin
      D inhibited FAK phosphorylation and cleavage, cell adhesion, locomotion, and ERK
      phosphorylation, thus showing FAK activation downstream of actin assembly. We
      also found a pivotal role for FAK Tyr(861) phosphorylation in cell motility and
      ERK activation. Our results reveal a novel functional connection between integrin
      alpha2 engagement, FAK, ERK, and mu-calpain activation in cell motility and a
      direct link between FAK cleavage and enhanced cell motility. The data suggest
      that blocking the integrin alpha2/FAK/ERK/mu-calpain pathway may be an important
      strategy to reduce cancer progression.

PMID- 16461768
TI  - Interaction between eukaryotic initiation factors 1A and 5B is required for
      efficient ribosomal subunit joining.
AB  - Eukaryotic initiation factor 5B (eIF5B) is a GTPase that facilitates joining of
      the 60 S ribosomal subunit to the 40 S ribosomal subunit during translation
      initiation. Formation of the resulting 80 S initiation complex triggers eIF5B to
      hydrolyze its bound GTP, reducing the affinity of the factor for the complex and
      allowing it to dissociate. Here we present a kinetic analysis of GTP hydrolysis
      by eIF5B in the context of the translation initiation pathway. Our data indicate
      that stimulation of GTP hydrolysis by eIF5B requires the completion of early
      steps in translation initiation, including the eIF1- and eIF1A-dependent delivery
      of initiator methionyl-tRNA to the 40 S ribosomal subunit and subsequent GTP
      hydrolysis by eIF2. Full activation of GTP hydrolysis by eIF5B requires the
      extreme C terminus of eIF1A, which has previously been shown to interact with the
      C terminus of eIF5B. Disruption of either isoleucine residue in the eIF1A C
      terminal sequence DIDDI reduces the rate constant for GTP hydrolysis by
      approximately 20-fold, whereas changing the aspartic acid residues has no effect.
      Changing the isoleucines in the C terminus of eIF1A also disrupts the ability of
      eIF5B to facilitate subunit joining. These data indicate that the interaction of
      the C terminus of eIF1A with eIF5B promotes ribosomal subunit joining and
      possibly provides a checkpoint for correct complex formation, allowing full
      activation of GTP hydrolysis only upon formation of a properly organized 80 S
      initiation complex.

PMID- 16461770
TI  - Up-regulation of the Wnt, estrogen receptor, insulin-like growth factor-I, and
      bone morphogenetic protein pathways in C57BL/6J osteoblasts as opposed to C3H/HeJ
      osteoblasts in part contributes to the differential anabolic response to fluid
      shear.
AB  - C57BL/6J (B6), but not C3H/HeJ (C3H), mice responded to mechanical loading with
      an increase in bone formation. A 30-min steady fluid shear of 20 dynes/cm(2)
      increased [(3)H]thymidine incorporation and alkaline phosphatase activity and up
      regulated the expression of early mechanoresponsive genes (integrin beta1 (Igtb1)
      and cyclooxygenase-2 (Cox-2)) in B6 but not C3H osteoblasts, indicating that the
      differential mechanosensitivity was intrinsic to osteoblasts. In-house microarray
      analysis with 5,500 gene fragments revealed that the expression of 669 genes in
      B6 osteoblasts and 474 genes in C3H osteoblasts was altered 4 h after the fluid
      shear. Several genes associated with the insulin-like growth factor (IGF)-I, the
      estrogen receptor (ER), the bone morphogenetic protein (BMP)/transforming growth
      factor-beta, and Wnt pathways were differentially up-regulated in B6 osteoblasts.
      In vitro mechanical loading also led to up-regulation of these genes in the bones
      of B6 but not C3H mice. Pretreatment of B6 osteoblasts with inhibitors of the Wnt
      pathway (endostatin), the BMP pathway (Noggin), or the ER pathway (ICI182780)
      blocked the fluid shear-induced proliferation. Inhibition of integrin and Cox-2
      activation by echistatin and indomethacin, respectively, each blocked the fluid
      shear-induced up-regulation of genes associated with these four pathways. In
      summary, up-regulation of the IGF-I, ER, BMP, and Wnt pathways is involved in
      mechanotransduction. These four pathways are downstream to the early
      mechanoresponsive genes, i.e. Igtb1 and Cox-2. In conclusion, differential up
      regulation of these anabolic pathways may in part contribute to the good and poor
      response, respectively, in the B6 and C3H mice to mechanical loading.

PMID- 16461771
TI  - Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the
      release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm.
AB  - Resistance of cancer cells to anoikis, apoptosis induced by cell detachment from
      the extracellular matrix, is thought to represent a critical feature of the
      malignant phenotype. Mechanisms that control anoikis of normal and cancer cells
      are understood only in part. Previously we found that anoikis of non-malignant
      intestinal epithelial cells is driven by detachment-induced down-regulation of
      Bcl-X(L), a protein that blocks apoptosis through preventing the release of death
      promoting factors from the mitochondria. Mitochondrial proteins the release of
      which causes anoikis are presently unknown. Similar to what was previously
      observed by others for keratinocytes and fibroblasts, we show here that anoikis
      of intestinal epithelial cells does not involve caspase-9, a target of a
      mitochondrial protein cytochrome c. Furthermore, Smac/Diablo, another
      mitochondrial pro-apoptotic factor, does not appear to play a role in detachment
      dependent apoptosis of these cells either. Instead, anoikis of intestinal
      epithelial cells is triggered by the release of a mitochondrial protein
      Omi/HtrA2, an event driven by detachment-induced down-regulation of Bcl-X(L).
      Moreover, we established that oncogenic ras inhibits anoikis by preventing the
      release of Omi/HtrA2. This effect of ras required ras-induced down-regulation of
      a pro-apoptotic protein Bak and could be blocked by an inhibitor of
      phosphoinositide 3-kinase, a target of Ras that was previously implicated by us
      in the down-regulation of Bak and blockade of anoikis. We conclude that Omi/HtrA2
      is an inducer of anoikis and an important regulator of ras-induced
      transformation.

PMID- 16461769
TI  - Calpain is required for normal osteoclast function and is down-regulated by
      calcitonin.
AB  - Osteoclast motility is thought to depend on rapid podosome assembly and
      disassembly. Both mu-calpain and m-calpain, which promote the formation and
      disassembly of focal adhesions, were observed in the podosome belt of
      osteoclasts. Calpain inhibitors disrupted the podosome belt, blocked the
      constitutive cleavage of the calpain substrates filamin A, talin, and Pyk2, which
      are enriched in the podosome belt, induced osteoclast retraction, and reduced
      osteoclast motility and bone resorption. The motility and resorbing activity of
      mu-calpain(-/-) osteoclast-like cells were also reduced, indicating that mu
      calpain is required for normal osteoclast activity. Histomorphometric analysis of
      tibias from mu-calpain(-/-) mice revealed increased osteoclast numbers and
      decreased trabecular bone volume that was apparent at 10 weeks but not at 5 weeks
      of age. In vitro studies suggested that the increased osteoclast number in the mu
      calpain(-/-) bones resulted from increased osteoclast survival, not increased
      osteoclast formation. Calcitonin disrupted the podosome ring, induced osteoclast
      retraction, and reduced osteoclast motility and bone resorption in a manner
      similar to the effects of calpain inhibitors and had no further effect on these
      parameters when added to osteoclasts pretreated with calpain inhibitors.
      Calcitonin inhibited the constitutive cleavage of a fluorogenic calpain substrate
      and transiently blocked the constitutive cleavage of filamin A, talin, and Pyk2
      by a protein kinase C-dependent mechanism, demonstrating that calcitonin induces
      the inhibition of calpain in osteoclasts. These results indicate that calpain
      activity is required for normal osteoclast activity and suggest that calcitonin
      inhibits osteoclast bone resorbing activity in part by down-regulating calpain
      activity.

PMID- 16461772
TI  - Urokinase-type plasminogen activator receptor regulates a novel pathway of
      fibronectin matrix assembly requiring Src-dependent transactivation of epidermal
      growth factor receptor.
AB  - Previous studies have indicated that the urokinase-type plasminogen activator
      receptor (uPAR) can functionally interact with integrins thereby modulating
      integrin activity. We have previously demonstrated that treatment of fibroblasts
      with the uPAR ligand, P25, results in an increase in the activation of the beta1
      integrin and a 35-fold increase in fibronectin matrix assembly (Monaghan, E.,
      Gueorguiev, V., Wilkins-Port, C., and McKeown-Longo, P. J. (2004) J. Biol. Chem.
      279, 1400-1407). Experiments were conducted to address the mechanism of uPAR
      regulation of matrix assembly. Treatment of fibroblasts with P25 led to an
      increase in the activation of the epidermal growth factor receptor (EGFR) and a
      colocalization of activated EGFR with beta1 integrins in cell matrix contacts.
      The effects of P25 on matrix assembly and beta1 integrin activation were
      inhibited by pretreatment with EGFR or Src kinase inhibitors, suggesting a role
      for both Src and EGFR in integrin activation by uPAR. Phosphorylation of EGFR in
      response to P25 occurred on Tyr-845, an Src-dependent phosphorylation site and
      was inhibited by PP2, the Src kinase inhibitor, consistent with Src kinase lying
      upstream of EGFR and integrin activation. Cells null for Src kinases also showed
      a loss of P25-induced matrix assembly, integrin activation, and EGFR
      phosphorylation. These P25-induced effects were restored following Src re
      expression. The effects of P25 were specific for uPAR as enhanced matrix assembly
      by P25 was not seen in uPAR-/- cells, but was restored upon uPAR re-expression.
      These data provide evidence for a novel pathway of fibronectin matrix assembly
      through the uPAR-dependent sequential activation of Src kinase, EGFR, and beta1
      integrin.

PMID- 16461773
TI  - Contribution of the histone H3 and H4 amino termini to Gcn4p- and Gcn5p-mediated
      transcription in yeast.
AB  - Histone amino termini are post-translationally modified by both transcriptional
      coactivators and corepressors, but the extent to which the relevant histone
      modifications contribute to gene expression, and the mechanisms by which they do
      so, are incompletely understood. To address this issue, we have examined the
      contributions of the histone H3 and H4 amino termini, and of the coactivator and
      histone acetyltransferase Gcn5p, to activation of a small group of Gcn4p
      activated genes. The histone H3 tail exerts a modest (about 2-fold) but
      significant effect on activation that correlates with a requirement for Gcn5p and
      is distributed over multiple lysine residues. The H4 tail also plays a positive
      role in activation of some of those genes tested, but this does not correlate as
      closely with Gcn5p coactivation. Microarray experiments did not reveal a close
      correspondence between those genes activated by Gcn4p and genes requiring the H3
      or H4 tail, and analysis of published microarray data indicates that Gcn4p
      regulated genes are not in general strongly dependent on Gcn5p. However, a large
      fraction of genes activated by Gcn4p were found to be repressed by the H3 and H4
      amino termini under non-inducing conditions, indicating that one role for Gcn4p
      is to overcome repression mediated by the histone tails.

PMID- 16461775
TI  - Disease severity and genetic pathways in attenuated familial adenomatous
      polyposis vary greatly but depend on the site of the germline mutation.
AB  - BACKGROUND: Attenuated familial adenomatous polyposis (AFAP) is associated with
      germline mutations in the 5', 3', and exon 9 of the adenomatous polyposis coli
      (APC) gene. These mutations probably encode a limited amount of functional APC
      protein. METHODS AND RESULTS: We found that colonic polyp number varied greatly
      among AFAP patients but members of the same family tended to have more similar
      disease severity. 5' Mutants generally had more polyps than other patients. We
      analysed somatic APC mutations/loss of heterozygosity (LOH) in 235 tumours from
      35 patients (16 families) with a variety of AFAP associated germline mutations.
      In common with two previous studies of individual kindreds, we found biallelic
      changes ("third hits") in some polyps. We found that the "third hit" probably
      initiated tumorigenesis. Somatic mutation spectra were similar in 5' and 3'
      mutant patients, often resembling classical FAP. In exon 9 mutants, in contrast,
      "third hits" were more common. Most "third hits" left three 20 amino acid repeats
      (20AARs) on the germline mutant APC allele, with LOH (or proximal somatic
      mutation) of the wild-type allele; but some polyps had loss of the germline
      mutant with mutation leaving one 20AAR on the wild-type allele. CONCLUSIONS: We
      propose that mutations, such as nt4661insA, that leave three 20AARs are
      preferentially selected in cis with some AFAP mutations because the residual
      protein function is near optimal for tumorigenesis. Not all AFAP polyps appear to
      need "three hits" however. AFAP is phenotypically and genetically heterogeneous.
      In addition to effects of different germline mutations, modifier genes may be
      acting on the AFAP phenotype, perhaps influencing the quantity of functional
      protein produced by the germline mutant allele.

PMID- 16461774
TI  - Histone H3 lysine 9 methyltransferase G9a is a transcriptional coactivator for
      nuclear receptors.
AB  - Methylation of Lys-9 of histone H3 has been associated with repression of
      transcription. G9a is a histone H3 Lys-9 methyltransferase localized in
      euchromatin and acts as a corepressor for specific transcription factors. Here we
      demonstrate that G9a also functions as a coactivator for nuclear receptors,
      cooperating synergistically with nuclear receptor coactivators glucocorticoid
      receptor interacting protein 1, coactivator-associated arginine methyltransferase
      1 (CARM1), and p300 in transient transfection assays. This synergy depends
      strongly on the arginine-specific protein methyltransferase activity of CARM1 but
      does not absolutely require the enzymatic activity of G9a and is specific to
      CARM1 and G9a among various protein methyltransferases. Reduction of endogenous
      G9a diminished hormonal activation of an endogenous target gene by the androgen
      receptor, and G9a associated with regulatory regions of this same gene. G9a fused
      to Gal4 DNA binding domain can repress transcription in a lysine
      methyltransferase-dependent manner; however, the histone modifications associated
      with transcriptional activation can inhibit the methyltransferase activity of
      G9a. These findings suggest a link between histone arginine and lysine
      methylation and a mechanism for controlling whether G9a functions as a
      corepressor or coactivator.

PMID- 16461776
TI  - Altered colonic glycoprotein expression in unaffected monozygotic twins of
      inflammatory bowel disease patients.
AB  - BACKGROUND AND AIMS: Previous chromatographic analysis of colonic mucins from
      monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin
      alteration in ulcerative colitis (UC). This study explores this further by
      assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose
      beta1, 3 N-acetylgalactosamine alpha-), among the same IBD twins. MATERIALS AND
      METHODS: Formalin fixed paraffin embedded rectal biopsies were studied from 22
      monozygotic twin pairs with IBD. These included eight UC twin pairs and 14
      Crohn's disease (CD) twin pairs, with six pairs concordant for disease and 16
      unaffected twin siblings. Closely adjacent sections were assessed by peanut
      lectin histochemistry for TF expression and immunohistochemically for nuclear
      factor kappaB (NFkappaB) activation with investigators blinded to the diagnosis.
      RESULTS: Unaffected twins were almost all TF positive (15/16) compared with 5/29
      histologically normal controls (p<0.0001). Unaffected UC (7/8) and CD twins (8/8)
      were similarly TF positive. TF positivity was confined mainly to the superficial
      epithelium and absent from the stem cell compartment of the lower crypts,
      suggesting that glycosylation changes are acquired rather than genetically
      determined. Activated NFkappaB was present in the surface epithelium of mucosal
      biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal
      controls (p=0.0004). All 22 affected IBD twins were TF positive and 18 were
      positive for activated NFkappaB. CONCLUSIONS: Altered mucosal glycosylation in
      unaffected identical twins of IBD patients was confirmed in this study. This
      occurred in both UC and CD twins. The changes are probably acquired rather than
      congenital and may reflect "preinflammatory" NFkappaB activation.

PMID- 16461777
TI  - Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B
      patients treated with adefovir dipivoxil.
AB  - BACKGROUND: Adefovir dipivoxil (ADV) is a potent nucleotide analogue against both
      the wild-type and lamivudine (LMV) resistant hepatitis B virus (HBV). The
      cumulative incidence of ADV resistant mutations in the nucleoside/-tide treatment
      naive chronic hepatitis B patient (CHB) at weeks 48, 96, and 144 was 0, 0.8-3%,
      and approximately 5.9%, respectively. AIMS: The aim of this study was to
      characterise the genotypic and phenotypic mutation profiles to ADV in 67 LMV
      resistant CHB patients who were treated with ADV. METHODS: Serum HBV DNA was
      quantified by real time polymerase chain reaction. The ADV mutant was detected
      using matrix assisted laser desorption/ionisation time of flight mass
      spectrometry based genotyping assays, termed restriction fragment mass
      polymorphism (RFMP). RESULTS: RFMP analysis revealed that a total of 11 amino
      acid substitutions developed in the rt domain of the HBV polymerase in nine
      patients. The cumulative incidence of genotypic ADV resistance at months 12 and
      24 was 6.4% and 25.4%, respectively. The rtA181V, rtN236T, and rtA181T mutations
      were detected in five, four, and two of the 67 patients at treatment months 12
      17, 3-19, and 7-20, respectively. Serial quantification of serum HBV DNA revealed
      that two patients with the rtA181V mutation, with or without the rtN236T
      mutation, and one patient with the rtA181T mutation displayed HBV DNA rebound.
      CONCLUSION: Emergence of the ADV mutation in LMV resistant patients who are
      treated with ADV appeared to present earlier and more frequently than was
      reported in previous studies on nucleoside/-tide treatment naive patients.

PMID- 16461778
TI  - Specific monocyte adhesion to endothelial cells induced by oxidized phospholipids
      involves activation of cPLA2 and lipoxygenase.
AB  - Oxidized phospholipids stimulate endothelial cells to bind monocytes, but not
      neutrophils, an initiating event in atherogenesis. Here, we investigate
      intracellular signaling events induced by oxidized phospholipids in human
      umbilical vein endothelial cells (HUVECs) that lead to specific monocyte
      adhesion. In a static adhesion assay, oxidized 1-palmitoyl-2-arachidonoyl-sn
      glycero-3-phosphorylcholine and one of its components, 1-palmitoyl-2-oxovaleroyl
      sn-glycero-3-phosphorylcholine, stimulated HUVECs to bind U937 cells and human
      peripheral blood monocytes but not HL-60 cells or blood neutrophils. Monocyte
      adhesion was dependent on protein kinases A and C, extracellular signal-regulated
      kinase 1/2, p38 mitogen activated protein kinases (MAPKs), and cytosolic
      phospholipase A(2) (cPLA(2)). Inhibition of 12-lipoxygenase (12-LOX), but not
      cyclooxygenases, blocked monocyte adhesion, and addition of 12
      hydroxyeicosatetraenoic acid (12-HETE) mimicked the effects of oxidized
      phospholipids. Peroxisome proliferator-activated receptor alpha (PPARalpha) was
      excluded as a possible target for 12-HETE, because monocyte adhesion was still
      induced in endothelial cells from PPARalpha null mice. Together, our results
      suggest that oxidized phospholipids stimulate HUVECs to specifically bind
      monocytes involving MAPK pathways, which lead to the activation of cPLA(2) and 12
      LOX. Further analysis of signaling pathways induced by oxidized phospholipids
      that lead to specific monocyte adhesion should ultimately lead to the development
      of novel therapeutic approaches against chronic inflammatory diseases.

PMID- 16461779
TI  - Intraperitoneal chemotherapy of ovarian cancer: a review, with a focus on
      practical aspects of treatment.

PMID- 16461780
TI  - Is excision alone adequate treatment for low-risk ductal carcinoma-in-situ of the
      breast?

PMID- 16461781
TI  - Prospective study of wide excision alone for ductal carcinoma in situ of the
      breast.
AB  - PURPOSE: It has been hypothesized that wide excision alone with margins > or = 1
      cm may be adequate treatment for small, grade 1 or 2 ductal carcinoma in situ
      (DCIS). To test this hypothesis, we conducted a prospective, single-arm trial.
      METHODS: Entry criteria included DCIS of predominant grade 1 or 2 with a
      mammographic extent of < or = 2.5 cm treated with wide excision with final
      margins of > or = 1 cm or a re-excision without residual DCIS. Tamoxifen was not
      permitted. The accrual goal was 200 patients. RESULTS: In July 2002, the study
      closed to accrual at 158 patients because the number of local recurrences met the
      predetermined stopping rules. The median age was 51 and the median follow-up time
      was 40 months. Thirteen patients developed local recurrence as the first site of
      treatment failure 7 to 63 months after study entry. The rate of ipsilateral local
      recurrence as first site of treatment failure was 2.4% per patient-year,
      corresponding to a 5-year rate of 12%. Nine patients (69%) experienced recurrence
      of DCIS and four (31%) experienced recurrence with invasive disease. Twelve
      recurrences were detected mammographically and one was palpable. Ten were in the
      same quadrant as the initial DCIS and three were elsewhere within the ipsilateral
      breast. No patient had positive axillary nodes at recurrence or subsequent
      metastatic disease. CONCLUSION: Despite margins of > or = 1 cm, the local
      recurrence rate is substantial when patients with small, grade 1 or 2 DCIS are
      treated with wide excision alone. This risk should be considered in assessing the
      possible use of radiation therapy with or without tamoxifen in these patients.

PMID- 16461782
TI  - Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation.
AB  - PURPOSE: To evaluate the incidence of and risk factors for basal cell carcinoma
      (BCC) and squamous cell carcinoma (SCC) in survivors of hematopoietic cell
      transplantation (HCT). PATIENTS AND METHODS: The impact of patient-, disease-,
      treatment-, and toxicity-related factors on risk of BCC and SCC was determined in
      a retrospective cohort study of 4,810 patients who received allogeneic HCT and
      who survived for at least 100 days. RESULTS: Among allogeneic HCT recipients, 237
      developed at least one skin or mucosal cancer (BCC, n = 158; SCC, n = 95). Twenty
      year cumulative incidences of BCC and SCC were 6.5% and 3.4%, respectively. Total
      body irradiation was a significant risk factor for BCC (P = .003), most strongly
      among patients younger than 18 years old at HCT (P = .02, interaction). Light
      skinned patients had an increased risk of BCC (P = .01). Acute graft-versus-host
      disease (GVHD) increased the risk of SCC (P = .02), whereas chronic GVHD
      increased the risk of both BCC (P = .01) and SCC (P < .001). CONCLUSION: This
      analysis suggests that immutable factors, such as age and complexion, have a
      significant impact on BCC and SCC. However, specific treatment (radiotherapy) and
      transplantation complications (GVHD) may modify that risk. These additional risk
      factors suggest the contribution of immunologic mechanism DNA and tissue repair
      in the development of BCC and SCC. We confirm previous reports that exposure to
      ionizing radiation increases the risk of BCC but not SCC. Survivors of HCT should
      be monitored for the development of BCC and SCC and use preventive strategies.

PMID- 16461783
TI  - B-cell chronic lymphocytic leukemia, a clonal disease of B lymphocytes with
      receptors that vary in specificity for (auto)antigens.
AB  - B-Cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that is
      relatively common among aging Caucasians. Patients with this leukemia can be
      divided into prognostic categories using clinical staging parameters, as well as
      molecular features [presence or absence of IgVH mutations in rearranged VHDJH
      segments that code for the leukemic B cell's receptor for antigen (BCR)]. In
      addition, the deduced amino acid structure of the BCRs from patients that fall
      into different prognostic categories is shared, to varying degrees, within these
      groups. In this paper, the molecular features of the genes that code for the BCRs
      of B-CLL patients are reviewed, and these are compared to antibodies of known
      specificity. These comparisons suggest that the BCRs of many cases resemble
      autoantibodies, and in some cases, antibodies to microbial antigens. Antigen
      binding analyses confirm these impressions, and also indicate that polyreactivity
      appears to distinguish cases with worse clinical outcomes differ from those with
      better outcomes. The persistence of autoreactivity and polyreactivity is somewhat
      surprising, because IgV DNA sequence analyses suggest that many of the B cells
      that become leukemic have undergone one form or another of receptor editing.
      Thus, B-CLL appears to be a disease of B-cell clones that have undergone various
      types of receptor reconfiguration and yet retain inappropriate antigen-binding
      properties.

PMID- 16461784
TI  - Harnessing the immune system against human glioma.
AB  - Our studies are directed toward immune resistance to glial tumors, particularly
      in children. Initial experiments indicate that it is possible to boost both
      innate natural killer T lymphocytes and adaptive CD4+ and CD8+ T cells by
      targeting the appropriate antigens to dendritic cells. Our hypothesis is that
      optimal vaccination approaches against cancer will need to recruit both innate
      and adaptive defense mechanisms.

PMID- 16461785
TI  - Immune response to premalignancy: insights from patients with monoclonal
      gammopathy.
AB  - Many patients with preneoplastic gammopathy remain clinically stable, in spite of
      the presence of multiple genomic abnormalities in tumor cells. Our hypothesis is
      that the development of clinical cancer depends not just on the genomic changes
      in tumor cells, but also their interactions with the host-tumor microenvironment.
      Recent studies have shown that the host immune system is capable of responding to
      preneoplastic cells. Improved understanding of this response may provide novel
      opportunities for early detection and immune prevention of cancer.

PMID- 16461786
TI  - Evaluation of anticyclin B1 serum antibody as a diagnostic and prognostic
      biomarker for lung cancer.
AB  - The primary aims of this study were to establish a high-throughput assay and
      analytic procedures that would allow us to assess with accuracy and
      reproducibility the presence of anti-cyclin B1 antibodies in a large cohort of
      subjects at-risk for development of lung cancer. The overall goal is to identify
      factors significantly associated with immune responses against this lung tumor
      antigen and to evaluate the relationship between anticyclin B1 antibodies and
      lung cancer risk in a prospective cohort. Successful cancer treatment relies on
      early detection. The immune system could respond to tumor antigens arising from
      altered host factors and provide an early readout for cancer presence. This study
      examines immune responses to the tumor antigen cyclin B1. Lung cancer patients
      have antibodies against cyclin B1. Unscheduled overexpression of this cell cycle
      regulator occurs early in tumorigenesis and might be detected by the immune
      system long before clinical diagnosis of cancer. Antibodies recognizing cyclin B1
      were measured using semiautomated ELISAs in sera samples from subjects without
      detectable lung cancer enrolled in the Pittsburgh Lung Screening Study (PLuSS), a
      longitudinal study of long-term smokers over age 50. Factors significantly
      associated with antibody presence were identified using linear regression
      analysis. We have established a highly reproducible, semiautomated ELISA-based
      assay for the high-throughput assessment of serum antibody titers. Using this
      technology and a small subset of PluSS subjects, cyclin B1 antibody levels were
      found to be high in a small proportion of subjects tested. Regression analysis
      identified gender as well as age in women smokers to be significant determinants
      of cyclin B1 antibody levels, association not seen in male subjects. This work
      represents an important first step toward defining the importance of the presence
      of anticyclin B1 antibodies in an at-risk population and assessing the predictive
      value of serum cyclin B1 antibody as relates to lung cancer risk.

PMID- 16461787
TI  - Manipulating the local tumor microenvironment with poxviruses expressing
      costimulatory molecules.
AB  - The identification of tumor-associated antigens and new insights into the
      molecular and cellular basis of tumor immunology have generated a variety of
      vaccine strategies. Although promising in animal models, data from early-phase
      clinical trials have not been encouraging. These studies have documented the
      ability of vaccines to prime T cells, but these responses have not correlated
      with therapeutic effectiveness. Because the location of T-cell activation and
      effector activity may impact T-cell function significantly, attention has been
      placed on the tumor microenvironment. There is now evidence that T-cell responses
      may be altered in the setting of established tumor growth. To alter the balance
      between local immune responses and tumor growth, a vaccine regimen using direct
      intratumoral delivery of poxvirus vaccines expressing costimulatory molecules was
      developed. An initial series of clinical trials has documented the safety profile
      of this approach and has suggested that local and systemic immunity can be
      induced. Herein, we review the general rationale for this approach, discuss the
      results of ongoing clinical trials, and highlight critical questions that can be
      addressed in well-designed preclinical and clinical studies.

PMID- 16461788
TI  - CD154 gene therapy for human B-cell malignancies.
AB  - Patients with chronic lymphocytic leukemia cells (CLL) who received a one-time
      bolus infusion of autologous leukemia cells transduced with adenovirus encoding
      recombinant CD154 experienced acute and long-term reductions in leukemia cell
      counts and lymph-node size. This was associated with increases in the numbers of
      leukemia-specific CD4+ T cells and high serum-levels of IL-12 and IFN-gamma. CD40
      ligation induces CLL cells to express the proapoptotic molecule Bid and death
      receptors CD95 (Fas) and DR5, rendering CLL B cells first resistant and then
      sensitive to Fas-mediated apoptosis. Increasing sensitivity to Fas-mediated
      apoptosis was also due to differential expression of pro- and antiapoptotic
      proteins at early versus late time points after activation. Additional treatment
      with inhibitors to the X-linked inhibitor to apoptosis (XIAP) rendered the CD40
      activated cells sensitive to Fas-mediated apoptosis even at early time points
      after CD40-activation, suggesting that XIAP inhibitors might enhance the
      effectiveness of CD154-based immune-gene therapy strategies for patients of B
      cell malignancies.

PMID- 16461789
TI  - The challenge of analyzing the proteome in humans with autoimmune diseases.
AB  - Analysis of blood samples from patients suffering from autoimmune diseases
      remains a mainstay in the clinic for initial diagnosis, prognostication, and
      clinical decision making. In particular, testing for the presence of serum
      autoantibodies has proved to be one of the most useful confirmatory assays for
      many different diseases. Recent genomic and transcript profiling studies have
      implicated certain cytokines, surface receptors, signaling pathways, and cell
      types in the pathogenesis of inflammatory diseases. The next obvious step is to
      delve into the much more complex level that follows the genome and transcriptome
      the expressed proteome. This review focuses on several proteomics technologies
      being applied and/or developed by our laboratory for the study of autoimmunity,
      cancer, and cardiovascular disease, all of which are known to be associated with
      defects in immunity and inflammation. The findings of other participants in the
      recent Human Immunology Conference hosted by the Dana Foundation and the New York
      Academy of Sciences (May 17 & 18, 2005) are included. In particular, major
      pitfalls in the study of the human proteome are pointed out, and important areas
      for immediate investigation to move the field forward as rapidly as possible are
      proposed.

PMID- 16461790
TI  - The immune response to BCG vaccination of newborns.
AB  - The aim of this study is to identify immune correlates of protection against
      tuberculosis induced by the current vaccine, Bacille Calmette Guerin (BCG). This
      knowledge should be valuable for developing and testing novel tuberculosis
      vaccines. Blood from 5675 10-week-old South African infants, routinely vaccinated
      with BCG at birth, was collected, processed, and stored. Subsequently, infants
      who have developed tuberculosis disease-"not protected by the vaccine"-and
      infants who have remained healthy despite exposure to adults with tuberculosis
      "protected by the vaccine"-have been identified. Recall immune responses to
      mycobacterial antigens in whole blood samples from the infants have been
      elicited; the next step will be to retrieve stored blood of "unprotected" and
      "protected" infants and compare immunity induced by BCG in the two groups. To
      guide the immune analysis, various pilot studies are being conducted to
      characterize the vaccination-induced host response. Preliminary results indicate
      that BCG does indeed induce a potent CD8 T-cell response, with cytokine-producing
      or cytotoxic potential, in infants. An induction of FoxP3 mRNA expression in some
      mycobacteria-stimulated whole-blood samples is also being found, which suggests
      the presence of BCG-induced regulatory CD4 T cells. Finally, stimulation of whole
      blood with mycobacterial antigens has resulted in a consistent pattern of
      cytokine release: significant numbers of infants make either large amounts of the
      effector cytokine interferon-gamma, or large amounts of the regulatory cytokine
      interleukin-10, but not both. Tests will, therefore, be made to determine whether
      CD8 or regulatory CD4 T-cell responses, as well as "outlier" cytokine responses,
      are associated with vaccination-induced protection against tuberculosis.

PMID- 16461791
TI  - Regulation of acquired immunity by gamma delta T-cell/dendritic-cell
      interactions.
AB  - In humans, innate immune recognition of mycobacteria, including Mycobacterium
      tuberculosis and Mycobacterium leprae, involves toll-like receptor-2 (TLR-2),
      expressed on immature dendritic cells (DCs), and the T-cell gammadelta receptor
      expressed by a subpopulation of T cells that utilize Vdelta2 (Vdelta2 T cells).
      To investigate modulatory relationships between these host-cell populations in a
      microbial context, in vitro experiments were performed with human DCs and Vdelta2
      T cells stimulated with model TLR-2 ligands and phosphoantigens, respectively. We
      observed that TLR-2-stimulated DCs enhanced interferon-gamma (IFN-gamma)
      production by Vdelta2 T cells; conversely, activated Vdelta2 T cells enhanced TLR
      2-induced DC maturation via soluble factors including IFN-gamma, which
      costimulated interleukin-12 (IL-12) p70 secretion by DCs. Exposure of DCs to
      activated Vdelta2 T cells was critical for Th1 T-cell priming when TLR-2
      stimulation was limiting. These results suggest that Vdelta2 T cells may play an
      adjuvant role in priming protective antimycobacterial immunity when TLR-2
      stimulation is lacking, as may occur if the infectious inoculum is small, or if
      the pathogen is an intrinsically weak activator of DCs.

PMID- 16461792
TI  - TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive
      aspergillosis after allogeneic stem cell transplantation.
AB  - Toll-like receptors (TLRs) transmit signals in response to Aspergillus fumigatus
      conidia and hyphae. In this preliminary study, we examined the association
      between single nucleotide polymorphisms (SNPs) in TLR1, TLR4, and TLR6 genes and
      development of invasive aspergillosis (IA) in 127 allogeneic hematopoietic stem
      cell transplant recipients consisting of 22 patients with IA and 105 unaffected
      control subjects. The following SNPs and their pairwise interactions were
      considered in the model: TLR1 (239G > C, 743A > G, 914A > T, 1805G > T), TLR4
      (896A > G, 1196C > T), and TLR6 (359T > C, 745C > T, 764C > T). No association
      was found between donor SNP and the risk of IA. Analysis of recipient SNP data
      showed that the presence of TLR1 239G > C (Arg80 > Thr) or the presence of both
      TLR1 743A > G (Asn248 > Ser) and TLR6 745C > T (Ser249 > Pro) is associated with
      IA (odds ratio = 1.30, 95% confidence interval = 1.13 to 1.50; P < .001). Further
      analyses using a prospective cohort may enable us to identify TLR polymorphisms
      associated with the susceptibility to IA within a defined interval among
      immunocompromised patients.

PMID- 16461793
TI  - T-cell immunotherapy for adenoviral infections of stem-cell transplant
      recipients.
AB  - Human adenoviruses are ubiquitous lytic DNA viruses that can be divided into 51
      different serotypes, grouped from A to F on the basis of genome size,
      composition, homology, and organization. Adenovirus infections, although
      frequent, are rarely fatal in immunocompetent individuals, due to potent innate
      and adaptive immune responses. By contrast, adenoviruses are a significant cause
      of morbidity and mortality in immunosuppressed individuals, for whom there are
      limited treatment options. Since antiviral drugs have variable efficacy in the
      treatment of severe adenovirus disease, iatrogenic reconstitution with in vitro
      expanded virus-specific cytotoxic T lymphocytes (CTLs) is an attractive option
      for prophylaxis and treatment, particularly because the endogenous recovery of
      adenovirus-specific T cells has proved important in controlling infection in
      vivo. Thus, we have characterized human T-cell responses to adenovirus in vitro
      and explored the potential of adoptive T-cell immunotherapy as a prophylactic or
      therapeutic strategy for adenovirus infections posttransplant.

PMID- 16461794
TI  - Human B cell tolerance and its failure in rheumatoid arthritis.
AB  - Random V(D)J gene assembly generates many autoreactive B cell receptors (BCRs).
      In healthy donors, most autoreactive developing B cells are removed either in the
      bone marrow or in the periphery, revealing two B cell tolerance checkpoints. The
      regulation and the mechanisms that ensure this human B cell tolerance are poorly
      characterized, but they require proper BCR signaling. Indeed, patients with X
      linked agammaglobulinemia who carry mutations in the BTK gene, which encodes an
      essential BCR signaling component, fail to establish proper central B cell
      tolerance, as demonstrated by the release of self-reactive B cells in the
      periphery. In autoimmune diseases such as rheumatoid arthritis (RA), B cell
      tolerance is broken and autoantibodies are secreted. Our recent results show that
      RA patients suffer from defective central and peripheral B cell tolerance
      checkpoints, which may favor the development of autoimmunity. Also, about half of
      our RA patients display unusual immunoglobulin light chain repertoires showing
      impaired secondary recombination regulation, which indicates that receptor
      editing, one of the mechanisms that normally ensures B cell tolerance, may often
      be defective in RA.

PMID- 16461795
TI  - Autoantigens: the critical partner in initiating and propagating systemic
      autoimmunity.
AB  - The increasing recognition that cancer is frequently associated with an
      autoantibody response, and observations that systemic autoimmunity is sometimes
      associated with the diagnosis of a variety of malignancies (many detected near
      the onset of autoimmune disease), strongly underscore a potential mechanistic
      connection between cancer immunity and systemic autoimmunity. Accumulating data
      suggest that autoantigens are critical partners in driving the autoimmune
      response. Furthermore, unique changes in antigen expression and conformation in
      the immunizing tumor and the target tissue may play a role in antigen selection
      and ongoing damage. This construct has important implications for diagnosis,
      monitoring, and treatment of autoimmunity and, potentially, cancer immunotherapy.

PMID- 16461796
TI  - Evaluation of topoisomerase-1-specific CD8+ T-cell response in systemic
      sclerosis.
AB  - Measurement of disease activity in systemic autoimmune disorders is often
      unreliable, and immunosuppressive therapy is often titrated to crude clinical
      response and/or onset of complications. Systemic sclerosis (SSc) presents a
      distinct clinical phenotype associated with specific autoantibodies. Anti
      topoisomerase-1 (SCL-70) is selectively detected in 30-60% of subjects with
      diffuse skin and interstitial lung involvement. Such patients offer an ideal
      clinical model to characterize and quantify the autoantigen-specific T-cell
      response and its correlation with disease phenotype and activity. Human leukocyte
      antigen A2 (HLA-A2)-restricted topo-1 peptides were selected based on an epitope
      prediction algorithm. For initial studies, the best binder topo-1(262-270)
      KMLDHEYTT (#262) was used alone or loaded onto an artificial antigen-presenting
      platform generated by coupling a dimeric major histocompatibility complex
      immunoglobulin G fusion protein (HLA-A2-Ig) and anti-CD28 antibodies onto
      magnetic beads (artificial antigen-presenting cells). Blood samples (100 microL)
      from HLA-A2+ SSc patients and cytomegalovirus (CMV) seropositive healthy control
      subjects were tested in an intracellular cytokine staining assay. Gamma
      interferon production by CD8+ T cells was measured after stimulation with peptide
      #262, CMVpp65, or MART-1 (irrelevant peptide). In two of five SCL-70+ patients,
      peptide #262-loaded aAPCs induced a specific CD8+ T-cell response (0.45% +/-
      0.23% of total CD8+ cells). This response was not observed in the seven SCL-70-
      (five SSc and two CMV+) control subjects studied (0.03% +/- 0.02%).
      Interestingly, bronchoalveolar lavage fluid obtained from one topo-1-responsive
      SSc patient who had worsening respiratory function and active alveolitis showed
      striking enrichment of topo-1-specific CD8+ T cells (3.94%). This small-volume ex
      vivo assay may prove to be a sensitive and specific tool to assess disease
      activity and to monitor response to therapy in patients with scleroderma.

PMID- 16461797
TI  - Analysis of significance patterns identifies ubiquitous and disease-specific gene
      expression signatures in patient peripheral blood leukocytes.
AB  - The utilization of gene-expression microarrays in patient-based research creates
      new prospects for the discovery of diagnostic biomarkers and the identification
      of genes or pathways linked to pathogenesis. Gene-expression signatures in
      peripheral blood mononuclear cells isolated from over one hundred patients with
      conditions presenting a strong immunological component (patient with autoimmune,
      graft versus host and infectious diseases, as well as immunosuppressed transplant
      recipients) were generated. This dataset provides the opportunity to carry out
      comparative analyses and define disease signatures in a broader context.
      Transcriptional changes of 22,283 probe sets were evaluated through statistical
      group comparison performed systematically for seven diseases versus their
      respective healthy control group. Patterns of significance were generated by
      hierarchical clustering of P-values. This approach led to the identification of a
      SLE-specific "diagnostic signature," formed by genes that did not change compared
      to healthy subjects in the other six diseases. Conversely, a "sentinel signature"
      that was common to all seven diseases was characterized. These findings bring new
      perspectives for the application of blood leukocyte expression signatures for
      diagnosis and early disease detection.

PMID- 16461798
TI  - Appreciating the heterogeneity in autoimmune disease: multiparameter assessment
      of intracellular signaling mechanisms.
AB  - Autoimmune disease pathologies are multifactorial with complex interactive
      networks of cells and chemical messengers that initiate cascades of aberrant
      cellular activity. Rheumatoid arthritis (RA) is a chronic inflammatory disease
      that is characterized by systemic inflammation, destruction of the joints, and
      production of autoantibodies recognizing dozens of putative autoantigens. The
      presence of autoreactive T cells in individuals leads to pathological
      autoimmunity by activating additional cellular constituents to mediate
      inflammation and joint destruction. The etiology of RA is unknown, and knowledge
      is lacking of the molecular mechanisms underlying the production and subsequent
      regulation of autoreactive T cells and predicting patient responses to
      treatments. Biochemical investigations into mechanisms of the disease have relied
      on animal models that are helpful in dissecting elements of the disease but that
      are not necessarily reflective of human RA development. The study of multiple
      activated signaling pathways in complex populations of cells, such as peripheral
      blood, at the single-cell level has not previously been possible. This article
      describes how intracellular phosphoepitope staining methodology in conjunction
      with surface-cell immunophenotyping can be used to deconvolute cellular subsets
      and allow functional characterization of patient-derived material. Multiparameter
      flow cytometric analysis allows for small subpopulations-representing different
      cellular subsets and differentiation or activation states-to be discerned and
      simultaneously assessed for intracellular biochemical activities. This article
      also describes how single-cell signal network analysis can be used to stratify
      patients and may be useful for understanding mechanisms of disease progression,
      treatment resistance, and development of diagnostic indicators.

PMID- 16461799
TI  - B-cell tolerance checkpoints in healthy humans and patients with systemic lupus
      erythematosus.
AB  - Antibodies are protective effector molecules in the body's immune defense against
      pathogens. However, if directed against the body's own tissues or organs,
      antibodies can also play a role in the pathogenesis of autoimmune disease. Here,
      we discuss our data on how autoreactive antibodies are regulated in healthy
      humans and how a failure to establish self-tolerance during early B-cell
      development in patients with systemic lupus erythematosus may predispose to the
      development of this autoimmune disease.

PMID- 16461800
TI  - Potential contribution of VH gene replacement in immunity and disease.
AB  - VH replacement occurs through RAG-mediated recombination between a cryptic
      recombination signal sequence (cRSS) presented in a rearranged VH gene and a 23
      bp RSS from an upstream VH gene. VH replacement renews the entire VH coding
      region and extends the immunoglobulin heavy-chain (IgH) CDR3 regions
      preferentially with charged amino acids. VH replacement occurs in bone marrow
      immature B cells and contributes significantly to the primary B-cell repertoire
      in humans. However, the biological significance of VH replacement is not clear.
      Our recent studies revealed elevated frequencies of VH replacement products in
      different autoimmune diseases, including rheumatoid arthritis, systemic lupus
      erythematosus, and Sjogren's syndrome. Moreover, elevated frequencies of VH
      replacement products were also found in patients with human immunodeficiency
      virus or hepatitis C virus infections. These results provide the first clue that
      VH replacement contributes to autoimmune disease and antiviral immunity, and they
      also suggest a potential link between viral infection and autoimmune disease.

PMID- 16461801
TI  - Costimulatory pathways in rheumatoid synovitis and T-cell senescence.
AB  - The pathogenesis of rheumatoid arthritis (RA) is determined by a complex
      interaction of genetic and environmental factors. Of all risk factors, age has
      the largest impact. RA occurs most often during the postmenopausal period of
      life, with incidence rates peaking in the eighth decade. While age is generally
      accepted as an etiologic factor for failure of immunocompetence, much less is
      understood about the role of T-cell senescence in autoimmunity. We have
      hypothesized that senescent T cells are particularly prone to be activated in
      specialized microenvironments, such as the synovial membrane. CD4 T cells in the
      senescence program were identified by the loss of CD28. Gene expression profiling
      documented that CD28- T cells have acquired a spectrum of regulatory receptors
      that are usually seen only on NK cells. Such regulatory receptors include
      stimulatory and inhibitory members of the killer immunoglobulin-like receptor
      (KIR) family, the stimulatory c-type lectin receptor NKG2D, and CX3CR1, the
      receptor for the chemokine fractalkine. Synovial fibroblasts express the relevant
      ligands, thus providing stimulatory signals to tissue-infiltrating T cells. The
      signaling pathways of these regulatory receptors are complex and dependent on the
      individual T cells, some of which express important adapter molecules such as
      DAP10 and DAP12. Inhibitory KIRs on T cells are often only partially functional.
      Our data suggest that, by virtue of altered receptor profiles, conventional
      tolerance mechanisms can be evaded in the aging host. By acquiring a new set of
      regulatory receptors, senescent CD4 T cells become responsive to novel
      environmental cues and find ideal stimulatory conditions in the synovial
      microenvironment.

PMID- 16461802
TI  - Vascular dendritic cells in giant cell arteritis.
AB  - Giant cell arteritis (GCA) is a granulomatous vasculitis that selectively targets
      medium-sized and large arteries, especially the cranial branches of the aorta.
      The inflammatory activity of vascular lesions is driven by adaptive immune
      responses, with CD4 T cells undergoing clonal expansion in the vessel wall and
      releasing interferon gamma. Recent studies have described a distinctive
      population of dendritic cells (DCs) localized at the adventitia-media border of
      normal medium-sized arteries that appear to play a critical role in the
      initiation of vasculitis. Immune effector functions of this DC population are
      being examined in human artery-severe combined immunodeficient (SCID) mouse
      chimeras. In their constitutive form, CD11c+ fascin+ adventitial DCs are not
      recognized by alloreactive T cells. Triggering with Toll-like receptor (TLR)
      ligands is sufficient to break this state of tolerance and initiate DC
      activation, T-cell recruitment, T-cell activation, and T-cell retention in the
      arterial wall. Systemic administration of ligands for TLR2 or -4 in human artery
      SCID chimeras drives differentiation of adventitial DCs into chemokine-producing
      effector cells with high-level expression of both CD83 and CD86 and mediates T
      cell regulatory function through release of interleukin 18. In established
      vasculitis, fully matured DCs retain antigen-presenting function; antibody
      mediated DC depletion disrupts T-cell and macrophage activation and has marked
      anti-inflammatory effects. We conclude that adventitial DCs, an indigenous cell
      population of the arterial wall, are responsive to pathogen-derived
      macromolecules and have gatekeeper function in regulating T-cell recruitment and
      retention to the arterial adventitia. A switch of adventitial DCs from being
      nonstimulatory to T-cell activating emerges as a critical event in the initiation
      of vasculitis.

PMID- 16461803
TI  - Immunologic role of the cholinergic anti-inflammatory pathway and the nicotinic
      acetylcholine alpha 7 receptor.
AB  - Cytokines are small protein molecules that facilitate communication between cells
      of the immune system and other tissues. Their messenger function elicits
      responses in other cells, ranging from DNA binding and tissue remodeling to
      coordinating the local cellular response to inflammation. The magnitude of the
      cytokine response is regulated closely, because an over- or underabundance of
      cytokine activity can impair organ function and cause shock and tissue injury.
      Counterregulatory molecular and humoral mechanisms protect the host from cytokine
      excess, including the pituitary-adrenal-glucocorticoid system, and the anti
      inflammatory cytokine system. These humoral systems are protective, but they are
      relatively slow-acting, concentration-gradient dependent, and not integrated. We
      recently discovered that the "cholinergic anti-inflammatory pathway," a nervous
      system-based, rapid, and locally acting mechanism, can inhibit the cytokine
      response. Signals transmitted via the vagus nerve converge on cytokine-producing
      cells that express the nicotinic acetylcholine receptor alpha 7 (nAChR alpha7).
      The alpha7 receptor is an essential component of the cholinergic anti
      inflammatory pathway, because activation of this receptor prevents cytokine
      release. Advances in understanding the molecular structure and function of alpha7
      have begun to provide a better understanding of potential mechanisms regarding
      its assembly, expression, and cytokine-inhibiting functions. It may be possible
      to exploit this pathway to therapeutic advantage for diseases caused by excessive
      cytokine activity.

PMID- 16461804
TI  - Pathogenic T-cell recruitment into the airway in human disease.
AB  - Effector T cells significantly contribute to inflammatory diseases. These cells
      are recruited into tissue, where they orchestrate an inflammatory response that
      can either protect against infection or sometimes stimulate human disease. The
      recruitment of T cells into tissue from the blood and lymphoid compartments is an
      active process controlled by chemokines and the chemokine receptors expressed on
      distinct effector T-cell subsets. Thus, the chemokines secreted in the tissue
      will determine the specific types of T lymphocyte recruited into that tissue
      based on the chemokine receptors expressed on these cells. It follows that the
      chemokine receptor profile on T cells isolated from the lungs of patients with
      inflammatory pulmonary disease will define the subtype of pathogenic T
      lymphocytes mediating the disease process and will identify the mechanisms that
      recruit these cells into the lung. This article reviews data from both human and
      animal studies that define the chemokine receptors involved in the recruitment of
      T lymphocytes into the lung in various inflammatory pulmonary diseases, including
      asthma, obliterative bronchiolitis, sarcoidosis, and chronic eosinophilic
      pneumonia. We then speculate on the potential role of these chemokine receptors
      in the pathogenesis of these disorders and potential novel therapeutic approaches
      suggested by these data.

PMID- 16461805
TI  - Toll-like receptor activation in the pathogenesis of systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is characterized by the production of
      pathogenic autoantibodies to nucleoproteins and DNA. The level of anti-DNA
      antibodies correlates with disease severity, and the deposition of these immune
      complexes (ICs) in the kidneys is thought to contribute to disease pathogenesis.
      Recent evidence suggests that the DNA component of ICs purified from SLE patients
      (SLE DNA-ICs) contributes to the development of SLE pathology. SLE DNA-ICs induce
      proliferation of self-reactive B cells and cytokine production by plasmacytoid
      dendritic cells (PDCs) in a TLR9-dependent manner. One of the cytokines induced
      by DNA-containing ICs is interferon alpha (IFN-alpha). Elevated serum levels of
      IFN-alpha and overexpression of interferon-induced genes have been observed in
      SLE patient blood and shown to correlate with disease severity. We have recently
      found that the mechanism of IFN-alpha production by PDCs depends on TLR9 and
      FcgammaRIIa (CD32), and CD32 delivers SLE DNA-ICs to intracellular lysosomes
      containing TLR9. This CD32-TLR9 pathway, which is operative in PDCs, is distinct
      from the BCR/TLR9 pathway in B cells and may prove to be a novel target for
      future SLE therapies. In this article, the role of toll-like receptors,
      cytokines, and Fc receptors expressed by PDCs in the pathogenesis of SLE is
      summarized.

PMID- 16461806
TI  - Optimising preoperative diagnosis in phyllodes tumour of the breast.
AB  - The role of the pathologist in the preoperative diagnosis of phyllodes tumours of
      the breast is critical to appropriate surgical planning. However, reliable
      differentiation of phyllodes tumour from cellular fibroadenoma remains difficult.
      Preoperative diagnostic accuracy allows correct surgical treatment, avoiding the
      pitfalls of reoperation because of inadequate excision, or surgical
      overtreatment. Specific clinical indices may arouse diagnostic suspicion but are
      unreliable for confirmation, as with current imaging modes. Fine needle
      aspiration cytology has a high false negative rate. Few studies have evaluated
      the role of core needle biopsy, but it may prove a useful adjunct. Both
      diagnostic and prognostic information may in future be gained from application of
      immunohistochemical and other techniques assessing the expression of
      proliferative markers including p53, Ki-67, and others.

PMID- 16461807
TI  - Expression of glucocorticoid receptors in non-neoplastic lymphoid follicles and B
      cell type malignant lymphomas.
AB  - OBJECTIVE: To evaluate the expression of human glucocorticoid receptors (hGRs),
      such as hGR (4H2), hGR-alpha, and hGR-beta, in non-neoplastic lymphoid follicles
      and B cell type malignant lymphomas. METHODS: The expression of hGRs in non
      neoplastic lymphoid follicles and malignant lymphomas, including diffuse large
      cell lymphoma, mantle cell lymphoma, and follicular lymphoma, was examined
      immunohistochemically. HGR (4H2) expression was confirmed by double
      immunostaining of tissues and in isolated cells from tonsillar germinal centres,
      and by immunoelectronmicroscopy. RESULTS: In secondary lymphoid follicles of any
      non-neoplastic diseases--such as chronic tonsillitis, reactive lymphadenitis, and
      Kimura's disease--the germinal centre cells often expressed hGR (4H2) and hGR
      alpha. Double immunocytochemical staining of isolated germinal centre cells
      showed that the majority of hGR (4H2) positive cells were CD20 positive B cells,
      and that follicular dendritic cells also expressed hGR. Immunoelectronmicroscopy
      revealed the presence of nuclear hGR (4H2) in the binucleated follicular
      dendritic cells and germinal centre cells. The frequency of hGR (4H2) expression
      in diffuse large B cell lymphoma was higher, that in mantle cell lymphoma was
      lower, and that in follicular lymphoma was intermediate among the types of
      malignant lymphoma. The hGR (4H2) expression was less frequent in cases of grade
      I follicular lymphoma. CONCLUSIONS: There are differences in hGR expression
      between the germinal centre and the mantle zone in non-neoplastic lymphoid
      follicles, and differences of hGR (4H2) expression among the types of malignant
      lymphoma and grades of follicular lymphoma, which probably contribute to the
      different steroid sensitivities.

PMID- 16461808
TI  - Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell
      lines: an organotypic model.
AB  - BACKGROUND: All-trans retinoic acid (ATRA) is a natural vitamin A derivative that
      has a profound effect on the regulation of cell growth, differentiation and
      death. AIM: To investigate the tissue dynamic and cellular invasion effects of
      ATRA in choriocarcinoma (CCA), an aggressive trophoblastic tumour, by using a
      three-dimensional organotypic culture model system and cell invasion assay,
      respectively. METHODS: An organotypic culture model of two CCA cell lines, JAR
      and JEG, was established. The effects of 1 microM ATRA on proliferation,
      differentiation and apoptosis on this CCA model were assessed by morphological
      assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase
      related M30 cytoDeath antibody immunohistochemistry and the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein
      product, WAF1/Cip1, was also evaluated with DO7 and p21(WAF1) antibodies,
      respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also
      investigated with Cell Invasion Kit on the JEG cell line. RESULTS: ATRA was found
      to induce marked apoptosis in organotypic cultures of both cell lines, as
      evidenced by increased M30-positive cells (p<0.0001) and increased TUNEL-positive
      cells (p<0.0001) in treated cultures; to decrease proliferation, as evidenced by
      decreased Ki-67-positive cells (p<0.0001); and to decrease p53-DO7
      immunoreactivity (p<0.0001) and increase p21(WAF1) (p<0.0001) immunoreactivity.
      1.5 microM ATRA was found to effectively inhibit JEG cell invasion in the cell
      invasion assay. CONCLUSION: ATRA treatment was found to inhibit invasion and
      proliferation and enhance apoptosis, probably by the activation of caspases and
      induction of differentiation. ATRA and synthetic retinoids may be alternative
      agents for the treatment of CCA.

PMID- 16461809
TI  - Comparative investigations of T cell receptor gamma gene rearrangements in frozen
      and formalin-fixed paraffin wax-embedded tissues by capillary electrophoresis.
AB  - AIM: To compare clonal T cell receptor gamma (TCRgamma) gene rearrangements in
      frozen and formalin-fixed paraffin wax-embedded (FFPE) tissue, using capillary
      electrophoresis for use in diagnostics, as T cell lymphomas may be difficult to
      diagnose by conventional methods. METHODS: The DNA for PCR was extracted from
      frozen and FFPE tissue, cell lines and blood. PCR primers Vgamma1-8, Vgamma9,
      Vgamma10 or Vgamma11 (5' end labelled) combined with a mixture of
      JgammaP1/JgammaP/JgammaP2/Jgamma2 (unlabelled) were used. Monoclonal cases were
      sequenced and clonality, reproducibility, sensitivity and specificity analyses
      were carried out. RESULTS: In all cases the molecular test was found to be in
      agreement with the histological diagnosis. Discrepancies were found between
      frozen and FFPE tissue in 18 of 56 (32%) tests. The method was highly
      reproducible. The sensitivity was found to be 0.5% for cell lines and 1% for
      patient specimens and the specificity 100%. The junctional region between the
      Vgamma and Jgamma segments was specific for each patient. CONCLUSIONS: Capillary
      electrophoresis of PCR products from frozen and FFPE tissue is suitable for
      detecting clonal TCRgamma gene rearrangements. It is important, however, to
      correlate the results with conventional morphological and immunohistochemical
      studies.

PMID- 16461811
TI  - The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and
      clinical outcome.
AB  - BACKGROUND: Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT
      syndrome (LQTS) variant associated with deafness and caused by homozygous or
      compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the
      I(Ks) current, are still based largely on case reports. METHODS AND RESULTS: We
      analyzed data from 186 J-LN patients obtained from the literature (31%) and from
      individual physicians (69%). Most patients (86%) had cardiac events, and 50% were
      already symptomatic by age 3. Their QTc was markedly prolonged (557+/-65 ms).
      Most of the arrhythmic events (95%) were triggered by emotions or exercise.
      Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard
      ratio, 0.54; 95% CI, 0.34 to 0.88; P=0.01). A QTc >550 ms and history of syncope
      during the first year of life are independent predictors of subsequent CA/SD.
      Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are
      associated with a more benign course. beta-Blockers have only partial efficacy;
      51% of the patients had events despite therapy and 27% had CA/SD. CONCLUSIONS: J
      LN syndrome is a most severe variant of LQTS, with a very early onset and major
      QTc prolongation, and in which beta-blockers have limited efficacy. Subgroups at
      relatively lower risk for CA/SD are identifiable and include females, patients
      with a QTc < or =550 ms, those without events in the first year of life, and
      those with mutations on KCNE1. Early therapy with implanted
      cardioverter/defibrillators must be considered.

PMID- 16461812
TI  - Percutaneous transvenous mitral annuloplasty: initial human experience with
      device implantation in the coronary sinus.
AB  - BACKGROUND: Mitral annuloplasty is the most common surgical procedure performed
      for ischemic mitral regurgitation (MR). Surgical mitral annuloplasty is limited
      by morbidity, mortality, and MR recurrence. We evaluated the safety and
      feasibility of a transvenous catheter-delivered implantable device to provide a
      percutaneous alternative to surgical mitral annuloplasty. METHODS AND RESULTS:
      Five patients with chronic ischemic MR underwent percutaneous transvenous
      implantation of an annuloplasty device in the coronary sinus. Implantation was
      successful in 4 patients. Baseline MR in the entire group was grade 3.0+/-0.7 and
      was reduced to grade 1.6+/-1.1 at the last postimplantation visit when the device
      was intact or the last postprocedural visit in the patient in whom the device was
      not successfully implanted. Separation of the bridge section of the device
      occurred in 3 of 4 implanted devices and was detected at 28 to 81 days after
      implantation. There were no postprocedural device-related complications.
      CONCLUSIONS: Percutaneous implantation of a device intended to remodel the mitral
      annulus is feasible. Initial experience suggests a possible favorable effect on
      MR. Percutaneous transvenous mitral annuloplasty warrants further evaluation as a
      less invasive alternative to surgical annuloplasty.

PMID- 16461813
TI  - Percutaneous aortic valve implantation retrograde from the femoral artery.
AB  - BACKGROUND: Percutaneous aortic valve implantation by an antegrade transvenous
      approach has been described but is problematic. Retrograde prosthetic aortic
      valve implantation via the femoral artery has potential advantages. Percutaneous
      prosthetic aortic valve implantation via the femoral arterial approach is
      described and the initial experience reported. METHODS AND RESULTS: The valve
      prosthesis is constructed from a stainless steel stent with an attached
      trileaflet equine pericardial valve and a fabric cuff. After routine aortic
      balloon valvuloplasty, a 22F or 24F sheath is advanced from the femoral artery to
      the aorta. A steerable, deflectable catheter facilitates manipulation of the
      prosthesis around the aortic arch and through the stenotic valve. Rapid
      ventricular pacing is used to reduce cardiac output while the delivery balloon is
      inflated to deploy the prosthesis within the annulus. Percutaneous aortic
      prosthetic valve implantation was attempted in 18 patients (aged 81+/-6 years) in
      whom surgical risk was deemed excessive because of comorbidities. Iliac arterial
      injury, seen in the first 2 patients, did not recur after improvement in
      screening and access site management. Implantation was successful in 14 patients.
      After successful implantation, the aortic valve area increased from 0.6+/-0.2 to
      1.6+/-0.4 cm2. There were no intraprocedural deaths. At follow-up of 75+/-55
      days, 16 patients (89%) remained alive. CONCLUSIONS: This initial experience
      suggests that percutaneous transarterial aortic valve implantation is feasible in
      selected high-risk patients with satisfactory short-term outcomes.

PMID- 16461814
TI  - Familial aggregation of calcific aortic valve stenosis in the western part of
      France.
AB  - BACKGROUND: Calcific aortic valve stenosis (CAVS) is the most common valvular
      defect in developed countries. Unlike mitral valve prolapse, there is no
      demonstration that a familial factor could play a role in the occurrence of this
      disease. The aim of this study was to demonstrate a familial aggregation for
      CAVS. METHODS AND RESULTS: We used the files of 2527 consecutive patients
      operated on for CAVS in our institution between 1992 and 2002 to map the
      distribution of operated CAVS in the western part of France. In a second step, we
      investigated clinically and genealogically the clusters with the highest rates of
      operated CAVS to detect familial forms of the disease. The geographic
      distribution of CAVS is highly heterogeneous, with an average frequency of
      operated CAVS of 1.13 per 1000 inhabitants but up to 9.38 per 1000 in specific
      parishes. A screening of the population from the parishes with the highest rate
      of operated CAVS allowed us to identify 5 families with > or =3 sibs affected by
      CAVS. A large genealogical analysis performed in one of these families allowed us
      to link 48 patients who derived from 34 nuclear families. Genealogical
      information could be traced to a common ancestor within 13 generations.
      CONCLUSIONS: Identification of clusters and large families affected by a classic
      form of CAVS demonstrates a familial aggregation for this disease.

PMID- 16461815
TI  - Extracellular matrix metalloproteinase inducer regulates matrix metalloproteinase
      activity in cardiovascular cells: implications in acute myocardial infarction.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are thought to promote progression
      of atherosclerosis and cardiovascular complications such as plaque rupture. It
      has been suggested that, on tumor cells, the extracellular MMP inducer (EMMPRIN)
      is involved in MMP synthesis by as yet unknown mechanisms. On cardiovascular
      cells, regulation of EMMPRIN in vivo or any functional relevance for MMP
      induction in vitro has not yet been studied. Thus, we studied EMMPRIN expression
      on monocytes in acute myocardial infarction (MI) and its potential relevance for
      MMP activation. METHODS AND RESULTS: In 20 patients with acute MI, surface
      expression of EMMPRIN was significantly enhanced on monocytes compared with in 20
      patients with chronic stable angina. EMMPRIN upregulation was associated with
      increased expression of the membrane type 1 MMP (MT1-MMP) on monocytes (flow
      cytometry) as well as MMP-9 activity (gelatin zymography) in the plasma. At 6
      months after successful revascularization, EMMPRIN, MT1-MMP, and MMP-9 had
      normalized. The secretion of MMP-9 by monocytes was induced by monocyte adhesion
      to immobilized recombinant EMMPRIN or to EMMPRIN-transfected Chinese hamster
      ovary cells. Moreover, adherent EMMPRIN-transfected monocytic cells stimulated
      MMP-2 activity of human vascular smooth muscle cells. Gene silencing of EMMPRIN
      by small-interfering RNA hindered lipopolysaccharide-induced monocyte secretion
      of MMP-9, indicating a predominant role of EMMPRIN in MMP-9 induction.
      CONCLUSIONS: EMMPRIN and MT1-MMP are upregulated on monocytes in acute MI. During
      cellular interactions, EMMPRIN stimulates MMP-9 in monocytes and MMP-2 in smooth
      muscle cells, indicating that EMMPRIN may display a key regulatory role for MMP
      activity in cardiovascular pathologies.

PMID- 16461816
TI  - Larger cell size in rabbits with heart failure increases myocardial conduction
      velocity and QRS duration.
AB  - BACKGROUND: Patients with heart failure (HF) have an increased QRS duration,
      usually attributed to decreased conduction velocity (CV) due to ionic remodeling
      but which may alternatively result from increased heart size or cellular
      uncoupling. We investigated the relationship between QRS width, heart size,
      intercellular coupling, and CV in a rabbit model of moderate HF and in computer
      simulations. METHODS AND RESULTS: HF was induced by pressure-volume overload.
      Heart weight (21.1+/-0.5 versus 10.2+/-0.4 g, mean+/-SEM; P<0.01) and QRS
      duration (58+/-1 versus 50+/-1 ms; P<0.01) were increased in HF versus control.
      Longitudinal CV (thetaL; 79+/-2 versus 67+/-4 cm/s; P<0.01) and transversal
      subepicardial CV (thetaT; 43+/-2 versus 37+/-2 cm/s; P<0.05) were higher in HF
      than in controls. Transmural CV (thetaTM) was unchanged (25+/-2 versus 24+/-1
      cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was
      unchanged in HF versus control. Immunohistochemical experiments revealed that
      connexin43 content was reduced in midmyocardium but unchanged in subepicardium.
      Myocyte dimensions were increased in HF by approximately 30%. Simulated strands
      of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased thetaL
      and thetaT with increased myocyte size; however, increased CV could not
      compensate for increased strand size of longitudinally coupled cells, and
      consequently, total activation time was longer. CONCLUSIONS: Increased myocyte
      size combined with the observed expression pattern of connexin43 yields increased
      thetaL and thetaT and unchanged thetaTM in our nonischemic model of HF. A
      hypertrophied left ventricle together with insufficiently increased thetaL and
      unaltered thetaTM results in a prolonged QRS duration.

PMID- 16461817
TI  - Are implantable cardioverter defibrillator shocks a surrogate for sudden cardiac
      death in patients with nonischemic cardiomyopathy?
AB  - BACKGROUND: Ventricular tachyarrhythmias long enough to cause implantable
      cardioverter defibrillator (ICD) shocks are generally thought to progress to
      cardiac arrest. In previous ICD trials, shocks have been considered an
      appropriate surrogate for sudden cardiac death (SCD) because the number of shocks
      has been thought to be equivalent to the mortality excess in patients without
      ICDs. The practice of equating ICD shocks with mortality is controversial and has
      not been validated critically. METHODS AND RESULTS: The Defibrillators in Non
      Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial was a prospective,
      randomized, multicenter trial of ICD therapy in 458 patients with nonischemic
      cardiomyopathy. Patients were randomized to receive standard medical therapy
      (STD) or STD plus an ICD. Shock electrograms were reviewed, and the cause of
      death was evaluated by a separate blinded events committee. There were 15 SCD or
      cardiac arrests in the STD group and only 3 in the ICD arm. In contrast, of the
      229 patients randomized to an ICD, 33 received 70 appropriate ICD shocks.
      Patients in the ICD arm were more likely to have an arrhythmic event (ICD shock
      plus SCD) than patients in the STD arm (hazard ratio 2.12, 95% CI 1.153 to 3.893,
      P=0.013). The number of arrhythmic events when one includes syncope as a
      potential arrhythmic event was similar in both groups (hazard ratio 1.20, 95% CI
      0.774 to 1.865, P=0.414). Approximately the same number of total events was noted
      in each arm when we compared syncope plus SCD/cardiac arrest in the STD arm with
      SCD plus ICD shocks plus syncope in the ICD arm. CONCLUSIONS: Appropriate ICD
      shocks occur more frequently than SCD in patients with nonischemic
      cardiomyopathy. This suggests that episodes of nonsustained ventricular
      tachycardia frequently terminate spontaneously in such patients.

PMID- 16461818
TI  - Mitral and aortic annular calcification are highly associated with systemic
      calcified atherosclerosis.
AB  - BACKGROUND: Atherosclerosis has been implicated as a cause of valvular
      calcification. The aim of this study was to determine whether atherosclerotic
      calcification in multiple vascular areas is significantly associated with aortic
      or mitral annular calcification independent of traditional risk factors. METHODS
      AND RESULTS: A total of 1242 consecutive asymptomatic patients free of clinical
      coronary heart disease were studied by electron-beam computed tomography for the
      extent of calcium due to atherosclerosis in 5 distinct vascular beds and calcium
      in the aortic and mitral annuli. Nearly 24% had calcium in the aortic annulus,
      whereas 8% were found to have mitral annular calcification. Age and a history of
      hypertension were the only traditional cardiovascular risk factors that were
      independently associated with prevalent calcification in the aortic and mitral
      annuli. After adjustment for age, gender, and cardiovascular disease risk
      factors, subjects with calcium in the thoracic aorta had the highest odds for the
      presence of aortic annular calcium (OR=3.9, P<0.01), whereas those with calcium
      in the abdominal aorta had the highest odds for mitral annular calcification
      (OR=5.1, P=0.01). Standardized increases in calcium in the abdominal aorta
      (OR=2.0, P<0.01) and iliacs (OR=1.8, P=0.01) were significantly associated with
      calcium in the aortic annulus after adjustment for the extent of calcium in the
      other vascular beds, whereas the thoracic aorta was significantly associated
      (OR=1.4, P=0.02) with calcium in the mitral annulus. CONCLUSIONS: This study
      supports the hypothesis that calcification of the mitral and aortic annuli is
      related to atherosclerosis in other vascular beds.

PMID- 16461819
TI  - Peroxisome proliferator-activated receptor-gamma activation with pioglitazone
      improves endothelium-dependent dilation in nondiabetic patients with major
      cardiovascular risk factors.
AB  - BACKGROUND: Patients with cardiovascular risk factors have endothelial
      dysfunction, a key element in the pathogenesis of atherosclerosis. The
      thiazolidinediones have been shown to exert multiple antiatherosclerotic actions
      in diabetic patients. This study tested the hypothesis that pioglitazone improves
      endothelial function in nondiabetic patients with major risk factors. METHODS AND
      RESULTS: The study had a randomized, double-blind, placebo-controlled, crossover
      design. Eighty patients with either hypertension or hypercholesterolemia were
      enrolled. Insulin sensitivity was assessed by the Quantitative Insulin
      Sensitivity Check Index (QUICKI), and patients were further classified as insulin
      sensitive or insulin resistant. In each treatment phase, patients received either
      pioglitazone 45 mg daily or placebo for 8 weeks. Endothelial function and
      laboratory tests were performed at the end of each 8-week period. Treatment with
      pioglitazone significantly lowered plasma insulin (-22.9%; P<0.001), improved
      QUICKI insulin sensitivity index (3.7%; P<0.001), increased HDL cholesterol
      (8.2%; P<0.001), and reduced triglycerides (-15.1%; P=0.003), free fatty acids (
      14%; P=0.005), and C-reactive protein (-28.6%; P=0.001). Pioglitazone treatment
      significantly improved endothelium-dependent dilation to bradykinin (P=0.01)
      without affecting the response to sodium nitroprusside (P=0.31). In multivariable
      analysis, only changes in total cholesterol were predictors of improved
      endothelial reactivity with pioglitazone. CONCLUSIONS: In nondiabetic patients
      with cardiovascular risk factors, pioglitazone treatment enhances insulin
      sensitivity, decreases C-reactive protein, and improves endothelial vasodilator
      function. These effects do not appear to be closely related, suggesting that
      pioglitazone may have beneficial vascular properties independent of its effect on
      insulin sensitivity and inflammation.

PMID- 16461820
TI  - Prediction of lifetime risk for cardiovascular disease by risk factor burden at
      50 years of age.
AB  - BACKGROUND: Lifetime risk for atherosclerotic cardiovascular disease (CVD) has
      not previously been estimated, and the effect of risk factor burden on lifetime
      risk is unknown. METHODS AND RESULTS: We included all Framingham Heart Study
      participants who were free of CVD (myocardial infarction, coronary insufficiency,
      angina, stroke, claudication) at 50 years of age. Lifetime risks to 95 years of
      age were estimated for men and women, with death free of CVD as a competing
      event. We followed up 3564 men and 4362 women for 111,777 person-years; 1757 had
      CVD events and 1641 died free of CVD. At 50 years of age, lifetime risks were
      51.7% (95% CI, 49.3 to 54.2) for men and 39.2% (95% CI, 37.0 to 41.4) for women,
      with median survivals of 30 and 36 years, respectively. With more adverse levels
      of single risk factors, lifetime risks increased and median survivals decreased.
      Compared with participants with > or =2 major risk factors, those with optimal
      levels had substantially lower lifetime risks (5.2% versus 68.9% in men, 8.2%
      versus 50.2% in women) and markedly longer median survivals (>39 versus 28 years
      in men, >39 versus 31 years in women). CONCLUSIONS: The absence of established
      risk factors at 50 years of age is associated with very low lifetime risk for CVD
      and markedly longer survival. These results should promote efforts aimed at
      preventing development of risk factors in young individuals. Given the high
      lifetime risks and lower survival in those with intermediate or high risk factor
      burden at 50 years of age, these data may be useful in communicating risks and
      supporting intensive preventive therapy.

PMID- 16461821
TI  - Association of a continuous quality improvement initiative with practice and
      outcome variations of contemporary percutaneous coronary interventions.
AB  - BACKGROUND: The objective of this study was to evaluate the association of a
      continuous quality improvement program with practice and outcome variations of
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: Data on
      consecutive PCI were collected in a consortium of 5 hospitals; 3731 PCIs
      reflected care provided at baseline (January 1, 1998, to December 31, 1998), and
      5901 PCIs reflected care provided after implementation of a continuous quality
      improvement intervention (January 1, 2002, to December 31, 2002). The
      intervention included feedback on outcomes, working group meetings, site visits,
      selection of quality indicators, and use of bedside tools for quality improvement
      and risk assessment. Postintervention data were compared with baseline and with
      10,287 PCIs from 7 hospitals added to the consortium in 2002. Quality indicators
      included use of preprocedural aspirin or clopidogrel, use of glycoprotein
      IIb/IIIa receptor blockers and postprocedural heparin, and amount of contrast
      media per case. Outcomes selected included emergency CABG, contrast nephropathy,
      myocardial infarction, stroke, transfusion, and in-hospital death. Compared with
      baseline and the control group, the intervention group at follow-up had higher
      use of preprocedural aspirin and glycoprotein IIb/IIIa blockers, lower use of
      postprocedural heparin, and a lower amount of contrast media per case (P<0.05).
      These changes were associated with lower rates of transfusions, vascular
      complications, contrast nephropathy, stroke, transient ischemic attack, and
      combined end points (all P<0.05). CONCLUSIONS: Our nonrandomized, observational
      data suggest that implementation of a regional continuous quality improvement
      program appears to be associated with enhanced adherence to quality indicators
      and improved outcomes of PCI. A randomized clinical trial is needed to determine
      whether this is a "causal" or a "casual" relationship.

PMID- 16461822
TI  - Characterization of acute and chronic myocardial infarcts by multidetector
      computed tomography: comparison with contrast-enhanced magnetic resonance.
AB  - BACKGROUND: We evaluated whether contrast-enhanced multidetector computed
      tomography (CE-MDCT) might characterize myocardial infarct (MI) with patterns
      similar to those obtained by contrast-enhanced magnetic resonance (CE-MR) and
      studied the underlying mechanisms. METHODS AND RESULTS: In vivo infarct
      characterization by CE-MDCT was shown to be feasible between 4 and 20 minutes
      after contrast injection in 7 pigs with MI. Subsequently, in 16 patients with
      acute MI and 21 patients with chronic MI, contrast patterns by CE-MDCT were
      related to CE-MR. Eighteen patients had hypoenhanced regions on early CE-MDCT
      images at the time of coronary imaging, and 34 patients had hyperenhanced regions
      on images acquired 10 minutes later. On a segmental basis, there was moderately
      good concordance of early hypoenhanced regions (92%, kappa=0.54, P<0.001) and
      late hyperenhanced regions (82%, kappa=0.61, P<0.001) between CE-MDCT and CE-MR.
      Absolute sizes of early hypoenhanced (6+/-16 versus 7+/-16 g, P=0.25) and late
      hyperenhanced (36+/-34 versus 31+/-40 g, P=0.14) regions were similar on CE-MDCT
      and CE-MR and were highly correlated (r=0.93, P<0.001 and r=0.89, P<0.001
      respectively). In 8 retrogradely perfused infarcted rabbit hearts, contrast
      kinetics of iomeprol were similar to gadodiamide, ie, slow wash in (8.7+/-6.7
      versus 1.2+/-0.3 minutes, P<0.001) in infarct core and slow washout (20+/-12
      versus 2.5+/-0.5 minutes, P<0.001) in both infarct core and rim compared with the
      remote region. CONCLUSIONS: Because iodated contrast agents have similar kinetics
      in infarcted and noninfarcted myocardium as gadolinium DPTA, CE-MDCT can
      characterize acute and chronic MI with contrast patterns similar to CE-MR. CE
      MDCT may thus provide important information on infarct size and viability at the
      time of noninvasive coronary imaging.

PMID- 16461823
TI  - Changing incidence and survival for heart failure in a well-defined older
      population, 1970-1974 and 1990-1994.
AB  - BACKGROUND: An epidemic increase in heart failure (HF) mortality,
      hospitalization, and prevalence rates has been observed among older persons in
      recent years. It is unclear whether this reflects an increase in incidence or
      survival. METHODS AND RESULTS: We conducted a retrospective cohort study
      comparing HF in 1970 to 1974 and 1990 to 1994 among persons > or =65 years old
      belonging to a large, well-defined population with complete medical records
      available for research. Using Framingham clinical criteria, we identified
      incident cases of HF in the respective periods. Age-specific and age-adjusted
      incidence, mortality, and survival rates were compared. Cox proportional-hazards
      models were used to assess association of comorbidities and medications with
      survival. During 38,800 and 127,419 person-years for 1970 to 1974 and 1990 to
      1994, respectively, 387 and 1555 confirmed incident cases were identified. When
      adjusted for age, incidence increased by 14% (95% CI 2% to 28%). Increased
      incidence tended to be greater for older persons and for men. Based on 5-year
      follow-up and adjustment for age and comorbidities, the mortality hazards
      decreased 33% (95% CI 14% to 48%) among men and 24% (95% CI -1% to 43%) among
      women. CONCLUSIONS: The epidemic increase in HF among the older population
      between the 1970s and 1990s is associated with increased incidence and improved
      survival, with both of these effects being greater in men.

PMID- 16461824
TI  - Images in cardiovascular medicine. Culprit lesion seen 1 hour before occlusion:
      limits of coronary angiography in detecting vulnerable plaques.

PMID- 16461825
TI  - Images in cardiovascular medicine. The blue man: amiodarone-induced skin
      discoloration.

PMID- 16461827
TI  - Letter regarding article by Norman et al, "novel mutation in desmoplakin causes
      arrhythmogenic left ventricular cardiomyopathy".

PMID- 16461826
TI  - Images in cardiovascular medicine. Intra-arterial thrombolysis for left middle
      cerebral artery embolic stroke during coronary angiography.

PMID- 16461828
TI  - Viewpoint from Israel.

PMID- 16461829
TI  - Prevention of coronary heart disease and the National Cholesterol Education
      Program.

PMID- 16461830
TI  - Arterial stiffness, vascular disease, and risk of cardiovascular events.

PMID- 16461831
TI  - Assessment of low-gradient aortic stenosis with dobutamine.

PMID- 16461832
TI  - Characteristics of cavotricuspid isthmus-dependent atrial flutter after left
      atrial ablation of atrial fibrillation.
AB  - BACKGROUND: Patients who have previously undergone ablation of atrial
      fibrillation may experience cavotricuspid isthmus (CTI)-dependent atrial flutter
      during follow-up. The effects of left atrial (LA) ablation on the characteristics
      of CTI-dependent flutter have not been described. METHODS AND RESULTS: Fifteen
      patients underwent ablation of CTI-dependent flutter late after LA ablation of
      AF. The ECG, biatrial activation patterns, and LA voltage maps during flutter
      were analyzed. Thirty age- and gender-matched patients who underwent ablation of
      CTI-dependent flutter without prior LA ablation served as control subjects. Among
      the patients with prior LA ablation, mapping revealed counterclockwise activation
      around the tricuspid annulus in 12 of 15 patients (80%) and clockwise activation
      in 3 of 15 patients (20%). The flutter waves in the inferior leads were upright
      in 9 of the 15 patients (60%) with prior LA ablation and in none of the control
      subjects (P<0.001). The upright flutter waves in the inferior leads in patients
      with counterclockwise flutter corresponded to craniocaudal activation of the
      right atrial free wall. LA activation contributed little to the genesis of the
      flutter waves in these patients because of a significant reduction in bipolar LA
      voltage (0.44+/-0.20 versus 1.54+/-0.19 mV in patients with biphasic/negative
      flutter waves; P<0.001). CONCLUSIONS: CTI-dependent flutter that occurs after LA
      ablation of atrial fibrillation often has atypical ECG characteristics because of
      altered LA activation. In patients presenting with atrial flutter after LA
      ablation, entrainment mapping should be performed at the CTI even if the ECG is
      uncharacteristic of CTI-dependent flutter.

PMID- 16461833
TI  - Localized sources maintaining atrial fibrillation organized by prior ablation.
AB  - BACKGROUND: Endocardial mapping of localized sources driving atrial fibrillation
      (AF) in humans has not been reported. METHODS AND RESULTS: Fifty patients with AF
      organized by prior pulmonary vein and linear ablation were studied. AF was
      considered organized if mapping during AF showed irregular but discrete atrial
      complexes exhibiting consistent activation sequences for >75% of the time using a
      20-pole catheter with 5 radiating spines covering 3.5-cm diameter or sequential
      conventional mapping. A site or region centrifugally activating the remaining
      atrial tissue defined a source. During AF with a cycle length of 211+/-32 ms,
      activation mapping identified 1 to 3 sources at the origin of atrial wavefronts
      in 38 patients (76%) predominantly in the left atrium, including the coronary
      sinus region. Electrograms at the earliest area varied from discrete centrifugal
      activation to an activity spanning 75% to 100% of the cycle length in 42% of
      cases, the latter indicating complex local conduction or a reentrant circuit. A
      gradient of cycle length (>20 ms) to the surrounding atrium was observed in 28%.
      Local radiofrequency ablation prolonged AF cycle length by 28+/-22 ms and either
      terminated AF or changed activation sequence to another organized rhythm. In 4
      patients, the driving source was isolated, surrounded by the atrium in sinus
      rhythm, and still firing at high frequency (228+/-31 ms) either permanently or in
      bursts. CONCLUSIONS: AF associated with consistent atrial activation sequences
      after prior ablation emanates mostly from localized sources that can be mapped
      and ablated. Some sources harbor electrograms suggesting the presence of
      localized reentry.

PMID- 16461835
TI  - Artificial baroreflex: clinical application of a bionic baroreflex system.
AB  - BACKGROUND: We proposed a novel therapeutic strategy against central baroreflex
      failure: implementation of an artificial baroreflex system to automatically
      regulate sympathetic vasomotor tone, ie, a bionic baroreflex system (BBS), and we
      tested its efficacy in a model of sudden hypotension during surgery. METHODS AND
      RESULTS: The BBS consisted of a computer-controlled negative-feedback circuit
      that sensed arterial pressure (AP) and automatically computed the frequency (STM)
      of a pulse train required to stimulate sympathetic nerves via an epidural
      catheter placed at the level of the lower thoracic spinal cord. An operation rule
      was subsequently designed for the BBS using a feedback correction with
      proportional and integral gain factors. The transfer function from STM to AP was
      identified by a white noise system identification method in 12 sevoflurane
      anesthetized patients undergoing orthopedic surgery involving the cervical
      vertebrae, and the feedback correction factors were determined with a numerical
      simulation to enable the BBS to quickly and stably attenuate an external
      disturbance on AP. The performance of the designed BBS was then examined in a
      model of orthostatic hypotension during knee joint surgery (n=21). Without the
      implementation of the BBS, a sudden deflation of a thigh tourniquet resulted in a
      17+/-3 mm Hg decrease in AP within 10 seconds and a 25+/-2 mm Hg decrease in AP
      within 50 seconds. By contrast, during real-time execution of the BBS, the
      decrease in AP was 9+/-2 mm Hg at 10 seconds and 1+/-2 mm Hg at 50 seconds after
      the deflation. CONCLUSIONS: These results suggest the feasibility of a BBS
      approach for central baroreflex failure.

PMID- 16461834
TI  - Mechanisms of wave fractionation at boundaries of high-frequency excitation in
      the posterior left atrium of the isolated sheep heart during atrial fibrillation.
AB  - BACKGROUND: High-frequency fractionated electrograms recorded during atrial
      fibrillation (AF) in the posterior left atrium (PLA) and elsewhere are being used
      as target sites for catheter ablation. We tested the hypothesis that highly
      periodic electric waves emerging from AF sources at or near the PLA give rise to
      the most fractionated activity in adjacent locations. METHODS AND RESULTS:
      Sustained AF was induced in 8 isolated sheep hearts (0.5 micromol/L
      acetylcholine). Endocardial videoimaging (DI-4-ANEPPS) and electric mapping of
      the PLA enabled spatial characterization of dominant frequencies (DFs) and a
      regularity index (ratio of DF to total power). Regularity index showed that
      fractionation was lowest within the area with the maximal DF (DFmax domain;
      0.19+/-0.02) and highest within a band of &3 mm (0.16+/-0.02; P=0.047) at
      boundaries with lower-frequency domains. The numbers of spatiotemporal periodic
      episodes (25.9+/-2.3) and rotors per experiment (1.9+/-0.7) were also highest
      within the DFmax domain. Most commonly, breakthrough waves at the PLA traveled
      toward the rest of the atria (76.8+/-8.1% outward versus 23.2+/-8.1% inward;
      P<0.01). In both experiments and simulations with an atrial ionic model,
      fractionation at DFmax boundaries was associated with increased beat-to-beat
      variability of conduction velocity and directionality with wavebreak formation.
      CONCLUSIONS: During stable AF, the PLA harbors regular, fast, and highly
      organized activity; the outer limit of the DFmax domain is the area where the
      most propagation pattern variability and fractionated activity occur. These new
      concepts introduce a new perspective in the clinical use of high-frequency
      fractionated electrograms to localize sources of AF precisely at the PLA and
      elsewhere.

PMID- 16461836
TI  - Patients with acute coronary syndrome show oligoclonal T-cell recruitment within
      unstable plaque: evidence for a local, intracoronary immunologic mechanism.
AB  - BACKGROUND: Recent studies indicate that T-cell activation may play an important
      role in the pathophysiology of acute coronary syndromes (ACS). However, although
      those studies detected T-cell expansion in peripheral blood cells, demonstration
      of specific T-cell expansion within the plaque of patients with ACS is lacking.
      The present study aims to address whether a specific, immune-driven T-lymphocyte
      recruitment occurs within the unstable plaque of patients with ACS. METHODS AND
      RESULTS: We simultaneously examined the T-cell repertoire using CDR3 size
      analysis both in coronary plaques (obtained by directional atherectomy) and in
      peripheral blood of patients with either ACS (n=11) or chronic stable angina
      (n=10). Unstable plaques showed a 10-fold increase in T-cell content by
      quantitative PCR. Using spectratyping analysis, we found several specific T-cell
      clonotype expansions only in unstable plaque from each patient with ACS,
      indicating a specific, antigen-driven recruitment of T cells within unstable
      lesions. CONCLUSIONS: For the first time, T-cell repertoire was investigated
      directly into coronary plaques; using this approach, we demonstrate that coronary
      plaque instability in the setting of ACS is associated with immune-driven T-cell
      recruitment, specifically within the plaque.

PMID- 16461837
TI  - Dyslipidemia prevalence, treatment, and control in the Multi-Ethnic Study of
      Atherosclerosis (MESA): gender, ethnicity, and coronary artery calcium.
AB  - BACKGROUND: To assess the implementation challenge facing the Third Report of the
      Adult Treatment Panel (ATP III) of the National Cholesterol Education Program, we
      determined the prevalence, treatment, and control of dyslipidemia, including
      ethnic and gender differences, in persons free of known clinical cardiovascular
      disease (CVD). In addition, this report provides information about the presence
      of coronary artery calcium (CAC) across groups defined by risk and
      recommendations for the use of lipid-lowering drugs. METHODS AND RESULTS: The
      Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study of
      6814 persons aged 45 to 84 years who were free of clinical CVD at baseline (2000
      2002). Participants with complete fasting lipid profiles (n=6704) were evaluated
      for CVD risk and self-reported use of lipid-lowering therapy. CAC was assessed by
      CT. Drug treatment thresholds and goals were defined according to ATP III. Models
      were constructed to adjust for age, clinic site, risk factors, socioeconomic
      characteristics, and healthcare access variables with the use of Poisson
      regression. Overall, 29.3% (1964/6704) had dyslipidemia, among whom lipid
      lowering drug therapy was reported by 54.0% (1060/1964). Control to ATP III goal
      was observed in 75.2% (797/1060) of participants with treated dyslipidemia and
      40.6% (797/1964) of participants with dyslipidemia. Men were more likely than
      women to qualify for drug therapy and less likely to be treated and controlled.
      Relative to non-Hispanic whites, Chinese Americans were less likely to qualify
      for drug treatment, but no differences in treatment and control rates were
      observed. Black and Hispanic Americans had prevalence of dyslipidemia that was
      comparable to that of non-Hispanic whites but were less likely to be treated and
      controlled. Ethnic disparities were attenuated substantially by adjustment for
      healthcare access variables; however, the gender disparities persisted despite
      adjustment for risk factors, socioeconomic characteristics, and healthcare access
      variables. Control of dyslipidemia was achieved less commonly in the CVD high-
      and intermediate-risk groups than in the low-risk group. Among high-risk
      individuals, 19.7% of those who did not qualify for lipid-lowering drug treatment
      had CAC >400. The proportion of drug treatment-qualifying persons who were not
      treated differed by presence and severity of CAC, with 48.0%, 46.8%, and 39.6% of
      eligible persons with no CAC, with CAC >0 and <400, and with CAC >400 not
      receiving treatment, respectively (P for difference=0.04). CONCLUSIONS:
      Dyslipidemia is common among persons without CVD. The quality of care for
      dyslipidemia is suboptimal in general and variable by CVD risk group, ethnicity,
      and gender. The utility of incorporating CAC screening into the risk
      stratification and treatment process should be investigated in light of the
      substantial proportions of persons with CAC who are currently classified as not
      requiring treatment. Research and quality improvement programs are needed to
      optimize management of dyslipidemia.

PMID- 16461838
TI  - Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam
      Study.
AB  - BACKGROUND: Arterial stiffness has been associated with the risk of
      cardiovascular disease in selected groups of patients. We evaluated whether
      arterial stiffness is a predictor of coronary heart disease and stroke in a
      population-based study among apparently healthy subjects. METHODS AND RESULTS:
      The present study included 2835 subjects participating in the third examination
      phase of the Rotterdam Study. Arterial stiffness was measured as aortic pulse
      wave velocity and carotid distensibility. Cox proportional hazards regression
      analysis was performed to compute hazard ratios. During follow-up, 101 subjects
      developed coronary heart disease (mean follow-up period, 4.1 years), and 63
      subjects developed a stroke (mean follow-up period, 3.2 years). The risk of
      cardiovascular disease increased with increasing aortic pulse wave velocity
      index. Hazard ratios and corresponding 95% CIs of coronary heart disease for
      subjects in the second and third tertiles of the aortic pulse wave velocity index
      compared with subjects in the reference category were 1.72 (0.91 to 3.24) and
      2.45 (1.29 to 4.66), respectively, after adjustment for age, gender, mean
      arterial pressure, and heart rate. Corresponding estimates for stroke were 1.22
      (0.55 to 2.70) and 2.28 (1.05 to 4.96). Estimates decreased only slightly after
      adjustment for cardiovascular risk factors, carotid intima-media thickness, the
      ankle-arm index, and pulse pressure. The aortic pulse wave velocity index
      provided additional predictive value above cardiovascular risk factors, measures
      of atherosclerosis, and pulse pressure. Carotid distensibility as measured in
      this study was not independently associated with cardiovascular disease.
      CONCLUSIONS: Aortic pulse wave velocity is an independent predictor of coronary
      heart disease and stroke in apparently healthy subjects.

PMID- 16461839
TI  - Prognostic value of aortic pulse wave velocity as index of arterial stiffness in
      the general population.
AB  - BACKGROUND: Few population studies addressed the prognostic significance of
      aortic pulse wave velocity (APWV) above and beyond other cardiovascular risk
      factors. METHODS AND RESULTS: We studied a sex- and age-stratified random sample
      of 1678 Danes aged 40 to 70 years. We used Cox regression to investigate the
      prognostic value of APWV, office pulse pressure (PP), and 24-hour ambulatory PP
      while adjusting for mean arterial pressure (MAP) and other covariates. Over a
      median follow-up of 9.4 years, the incidence of fatal and nonfatal cardiovascular
      end points, cardiovascular mortality, and fatal and nonfatal coronary heart
      disease amounted to 154, 62, and 101 cases, respectively. We adjusted for sex,
      age, body mass index, MAP measured in the office (conventional PP and APWV) or by
      ambulatory monitoring (24-hour PP), smoking, and alcohol intake. With these
      adjustments, APWV maintained its prognostic significance in relation to each end
      point (P<0.05), whereas office and 24-hour PP lost their predictive value
      (P>0.19), except for office PP in relation to coronary heart disease (P=0.02).
      For each 1-SD increment in APWV (3.4 m/s), the risk of an event increased by 16%
      to 20%. In sensitivity analyses, APWV still predicted all cardiovascular events
      after standardization to a heart rate of 60 beats per minute, after adjustment
      for 24-hour MAP instead of office MAP, and/or after additional adjustment for the
      ratio of total to HDL serum cholesterol and diabetes mellitus at baseline.
      CONCLUSIONS: In a general Danish population, APWV predicted a composite of
      cardiovascular outcomes above and beyond traditional cardiovascular risk factors,
      including 24-hour MAP.

PMID- 16461841
TI  - Histone acetyltransferase activity of p300 is required for the promotion of left
      ventricular remodeling after myocardial infarction in adult mice in vivo.
AB  - BACKGROUND: Left ventricular (LV) remodeling after myocardial infarction is
      associated with hypertrophy of surviving myocytes and represents a major process
      that leads to heart failure. One of the intrinsic histone acetyltransferases,
      p300, serves as a coactivator of hypertrophy-responsive transcriptional factors
      such as a cardiac zinc finger protein GATA-4 and is involved in its hypertrophic
      stimulus-induced acetylation and DNA binding. However, the role of p300-histone
      acetyltransferase activity in LV remodeling after myocardial infarction in vivo
      is unknown. METHODS AND RESULTS: To solve this problem, we have generated
      transgenic mice overexpressing intact p300 or mutant p300 in the heart. As the
      result of its 2-amino acid substitution in the p300-histone acetyltransferase
      domain, this mutant lost its histone acetyltransferase activity and was unable to
      activate GATA-4-dependent transcription. The two kinds of transgenic mice and the
      wild-type mice were subjected to myocardial infarction or sham operation at the
      age of 12 weeks. Intact p300 transgenic mice showed significantly more
      progressive LV dilation and diminished systolic function after myocardial
      infarction than wild-type mice, whereas mutant p300 transgenic mice did not show
      this. CONCLUSIONS: These findings demonstrate that cardiac overexpression of p300
      promotes LV remodeling after myocardial infarction in adult mice in vivo and that
      histone acetyltransferase activity of p300 is required for these processes.

PMID- 16461840
TI  - Renal function as a predictor of outcome in a broad spectrum of patients with
      heart failure.
AB  - BACKGROUND: Decreased renal function has been found to be an independent risk
      factor for cardiovascular outcomes in patients with chronic heart failure (CHF)
      with markedly reduced left ventricular ejection fraction (LVEF). The aim of this
      analysis was to evaluate the prognostic importance of renal function in a broader
      spectrum of patients with CHF. METHODS AND RESULTS: The Candesartan in Heart
      Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program
      consisted of three component trials that enrolled patients with symptomatic CHF,
      based on use of ACE inhibitors and reduced (< or =40%) or preserved LVEF (>40%).
      Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L).
      Routine baseline serum creatinine assessments were done in 2680 North American
      patients. An analysis of the estimated glomerular filtration rate (eGFR), using
      the Modification of Diet in Renal Disease equation and LVEF on risk of
      cardiovascular death or hospitalization for heart failure, as well as on all
      cause mortality, was conducted on these 2680 patients. The proportion of patients
      with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0%
      for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of
      34.4 months (total 6493 person-years), the primary outcome of cardiovascular
      death or hospital admission for worsening CHF occurred in 950 of 2680 subjects.
      Both reduced eGFR and lower LVEF were found to be significant independent
      predictors of worse outcome after adjustment for major confounding baseline
      clinical characteristics. The risk for cardiovascular death or hospitalization
      for worsening CHF as well as the risk for all-cause mortality increased
      significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54
      for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the
      primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91,
      P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was
      not significantly different among the three component trials. There was no
      significant interaction between renal function, the effect of candesartan, and
      clinical outcome. CONCLUSIONS: Impaired renal function is independently
      associated with heightened risk for death, cardiovascular death, and
      hospitalization for heart failure in patients with CHF with both preserved as
      well as reduced LVEF. There was no evidence that the beneficial effect of
      candesartan was modified by baseline eGFR.

PMID- 16461842
TI  - Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of
      human monocytic cells to endothelial cells.
AB  - BACKGROUND: Lipoproteins containing apolipoprotein (apo) CIII predict coronary
      heart disease and associate with components of the metabolic syndrome. ApoCIII
      inhibits lipoprotein catabolism in plasma. However, it is unknown whether apoCIII
      itself, or in association with VLDL, LDL, or HDL, directly affects atherogenic
      mechanisms in vascular cells. Thus, we investigated the direct effect of
      lipoproteins that do or do not have apoCIII, and apoCIII itself, on adhesion of
      THP-1 cells, a human monocytic cell line, to vascular endothelial cells (ECs).
      METHODS AND RESULTS: VLDL CIII+ and LDL CIII+ (100 microg apoB/mL) from fasting
      plasma of 18 normolipidemic volunteers increased THP-1 cell adhesion to ECs under
      static conditions by 2.4+/-0.3-fold and 1.8+/-0.7-fold, respectively (P<0.01),
      whereas VLDL or LDL without apoCIII did not affect THP-1 cell adhesion. ApoCIII
      (100 microg/mL), but not apoCI, apoCII or apoE, also increased THP-1 cell
      adhesion by 2.1+/-0.6-fold. Studies with human peripheral blood monocytes yielded
      similar results. ApoCIII also had strong proadhesive effects under shear flow
      conditions. VLDL CIII+, LDL CIII+, or apoCIII itself activated PKCalpha and RhoA
      in THP-1 cells, which resulted in beta1-integrin activation and enhancement of
      THP-1 cell adhesion. Interestingly, HDL CIII+ did not affect THP-1 cell adhesion,
      whereas HDL without apoCIII decreased their adhesion. CONCLUSIONS: ApoB
      lipoproteins that contain apoCIII increase THP-1 cell adhesion to ECs via
      PKCalpha and RhoA-mediated beta1-integrin activation. These results indicate that
      apoCIII not only modulates lipoprotein metabolism but also may directly
      contribute to the development of atherosclerosis.

PMID- 16461843
TI  - Administration of hematopoietic cytokines in the subacute phase after cerebral
      infarction is effective for functional recovery facilitating proliferation of
      intrinsic neural stem/progenitor cells and transition of bone marrow-derived
      neuronal cells.
AB  - BACKGROUND: Hematopoietic cytokines, granulocyte colony-stimulating factor (G
      CSF), and stem cell factor (SCF) were reported to show a neuroprotective effect
      or to support neurogenesis. These cytokines also mobilize bone marrow (BM) cells
      into the brain, and the BM-derived cells differentiate into neuronal cells. We
      administered these hematopoietic cytokines after focal cerebral ischemia and
      assessed their effects and the therapeutic time window for neuronal regeneration.
      METHODS AND RESULTS: We induced permanent middle cerebral artery occlusion in
      mice whose BM had been replaced with BM cells from green fluorescent protein
      (GFP)-transgenic mice. The occluded mice were treated with G-CSF and SCF in the
      acute phase (days 1 to 10) or subacute phase (days 11 to 20), and the brain
      functions and histological changes were evaluated. Separately, we injected
      bromodeoxyuridine during cytokine treatment to assess cell kinetics in the brain.
      Six mice were prepared for each experimental group. Administration of G-CSF and
      SCF in the subacute phase effectively improved not only motor performance but
      also higher brain function, compared with acute-phase treatment. Acute-phase and
      subacute-phase treatments identically reduced the infarct volume relative to
      vehicle treatment. However, subacute-phase treatment significantly induced
      transition of BM-derived neuronal cells into the peri-infarct area and stimulated
      proliferation of intrinsic neural stem/progenitor cells in the neuroproliferative
      zone. CONCLUSIONS: Administration of G-CSF and SCF in the subacute phase after
      focal cerebral ischemia is effective for functional recovery, enhancing cytokine
      induced generation of neuronal cells from both BM-derived cells and intrinsic
      neural stem/progenitor cells. Because G-CSF and SCF are available for clinical
      use, these findings suggest a new therapeutic strategy for stroke.

PMID- 16461844
TI  - Projected valve area at normal flow rate improves the assessment of stenosis
      severity in patients with low-flow, low-gradient aortic stenosis: the multicenter
      TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study.
AB  - BACKGROUND: We sought to investigate the use of a new parameter, the projected
      effective orifice area (EOAproj) at normal transvalvular flow rate (250 mL/s), to
      better differentiate between truly severe (TS) and pseudo-severe (PS) aortic
      stenosis (AS) during dobutamine stress echocardiography (DSE). Changes in various
      parameters of stenosis severity have been used to differentiate between TS and PS
      AS during DSE. However, the magnitude of these changes lacks standardization
      because they are dependent on the variable magnitude of the transvalvular flow
      change occurring during DSE. METHODS AND RESULTS: The use of EOAproj to
      differentiate TS from PS AS was investigated in an in vitro model and in 23
      patients with low-flow AS (indexed EOA <0.6 cm2/m2, left ventricular ejection
      fraction < or =40%) undergoing DSE and subsequent aortic valve replacement. For
      an individual valve, EOA was plotted against transvalvular flow (Q) at each
      dobutamine stage, and valve compliance (VC) was derived as the slope of the
      regression line fitted to the EOA versus Q plot; EOAproj was calculated as
      EOAproj=EOArest+VCx(250-Q(rest)), where EOArest and Q(rest) are the EOA and Q at
      rest. Classification between TS and PS was based on either response to flow
      increase (in vitro) or visual inspection at surgery (in vivo). EOAproj was the
      most accurate parameter in differentiating between TS and PS both in vitro and in
      vivo. In vivo, 15 of 23 patients (65%) had TS and 8 of 23 (35%) had PS. The
      percentage of correct classification was 83% for EOAproj and 91% for indexed
      EOAproj compared with percentages of 61% to 74% for the other echocardiographic
      parameters usually used for this purpose. CONCLUSIONS: EOAproj provides a
      standardized evaluation of AS severity with DSE and improves the diagnostic
      accuracy for distinguishing TS and PS AS in patients with low-flow, low-gradient
      AS.

PMID- 16461845
TI  - Tissue factor in cardiovascular diseases: molecular mechanisms and clinical
      implications.
AB  - Tissue factor (TF), formerly known as thromboplastin, is the key initiator of the
      coagulation cascade; it binds factor VIIa resulting in activation of factor IX
      and factor X, ultimately leading to fibrin formation. TF expression and activity
      can be induced in endothelial cells, vascular smooth muscle cells, and monocytes
      by various stimuli such as cytokines, growth factors, and biogenic amines. These
      mediators act through diverse signal transduction mechanisms including MAP
      kinases, PI3-kinase, and protein kinase C. Cellular TF is present in three pools
      as surface, encrypted, and intracellular protein. TF can also be detected in the
      bloodstream, referred to as circulating or blood-borne TF. Elevated levels of TF
      are observed in patients with cardiovascular risk factors such as hypertension,
      diabetes, dyslipidemia, and smoking as well as in those with acute coronary
      syndromes. TF may indeed be involved in the pathogenesis of atherosclerosis by
      promoting thrombus formation; in addition, it can induce migration and
      proliferation of vascular smooth muscle cells. As a consequence, therapeutic
      strategies have been developed to specifically interfere with the action of TF
      such as antibodies against TF, site-inactivated factor VIIa, or recombinant TF
      pathway inhibitor. Inhibition of TF action appears to be an attractive target for
      the treatment of cardiovascular diseases.

PMID- 16461847
TI  - Smart damping modulation of carotid wall energetics in human hypertension:
      effects of angiotensin-converting enzyme inhibition.
AB  - Damping is the conversion of mechanical energy of a structure into thermal
      energy, and it is related to the material viscous behavior. To evaluate the role
      of damping in the common carotid artery (CCA) wall in human hypertension and the
      possible improvement of angiotensin-converting enzyme (ACE) inhibition, we used
      noninvasive CCA pressure (tonometry) and diameter (B-mode echography) waveforms
      in normotensive subjects (NT group; n=12) and in hypertensive patients (HT group;
      n=22) single-blind randomized into HT-placebo (n=10) or HT-treated (ramipril, 5
      to 10 mg/d during 3 months; n=12). Vascular smooth muscle (VSM) null tonus
      condition was achieved from in vitro pressure and diameter waveforms (Konigsberg
      microtransducer and sonomicrometry) measured in explanted human CCA (n=14).
      Arterial wall dynamics was described by viscous (eta), inertial (M), and
      compliance (C) parameters, mean circumferential wall stress, viscous energy
      dissipation (WD), peak strain energy (WSt), damping ratio (xi=WD/WSt), and
      modeling isobaric indexes CIso and WSt(Iso). The lack of VSM tonus isobarically
      increased wall stress and reduced eta, CIso, and damping (P<0.01). Wall stress,
      eta, and WD were greater in HT than in NT (P<0.015) and arrived near normal in HT
      treated (P<0.032 respect to HT), with no changes in HT-placebo. Whereas CIso
      increased in HT-treated (P<0.01) approaching the NT level, xi did not vary among
      groups. During hypertension, because of the WSt increase, the arterial wall
      reacts increasing WD to maintain xi. ACE inhibition modulates VSM activation and
      vessel wall remodeling, significantly improving wall energetics and wall stress.
      This protective vascular action reduces extra load to the heart and maintains
      enhanced arterial wall damping.

PMID- 16461848
TI  - Beta2-adrenoceptor genotype and function affect hemodynamic profile heterogeneity
      in postural tachycardia syndrome.
AB  - Previous studies suggest that the beta2-adrenoceptor functions abnormally in
      patients with postural tachycardia syndrome (POTS) and may contribute to their
      altered hemodynamic profile. To test the hypothesis that the beta2-adrenoceptor
      response is decreased in POTS, we studied: (1) the arterial vasodilation response
      to the beta agonist, isoproterenol, and (2) the distribution of common
      polymorphisms (codons 16 and 27) of the gene coding the receptor (beta2-AR) in a
      large population with POTS. We measured plasma catecholamines and monitored
      hemodynamics and changes in forearm and leg blood flow to incremental doses of
      intraarterial isoproterenol in 9 patients with POTS compared with 8 healthy
      subjects. For polymorphism assessment we collected DNA from 57 patients with POTS
      and compared with 67 age-sex matched healthy subjects. Circulating catecholamines
      were significantly higher in POTS subjects compared with controls. Intrabrachial
      and intrafemoral isoproterenol infusion elicited a dose-dependent increase in
      blood flow. In healthy subjects, blood flow increased (mean+/-SEM) 400+/-70% in
      the forearm and 170+/-40% in the leg, but only 280+/-60% in forearms and 120+/
      20% in legs of patients with POTS (ANOVA for both P<0.001). The genotype and
      allele distributions for codons 16 and 27 beta2-AR variants were not different in
      the 2 groups. However, the blood pressure and plasma norepinephrine levels
      diverged in patients according to their genotype. Patients with Gly16Gly and
      patients with Glu27Glu had lower plasma catecholamines and higher supine and
      upright blood pressure, compared with other genotypes. Therefore, both decreased
      beta2-adrenoceptor-related vasodilation and beta2-AR polymorphisms may contribute
      to the hemodynamic diversity of patients with POTS.

PMID- 16461849
TI  - Cardiac glycosides and cardiomyopathy.

PMID- 16461850
TI  - Hypertension and antihypertensive therapy in elderly women: how much do we really
      know?

PMID- 16461851
TI  - Blood pressure reactivity to psychological stress: a new risk factor for coronary
      disease?

PMID- 16461852
TI  - The house of the hanged man at Auvers.

PMID- 16461853
TI  - Combat effects on mental health: the more things change, the more they remain the
      same.

PMID- 16461855
TI  - Perspectives on depression, mild cognitive impairment, and cognitive decline.
AB  - CONTEXT: The public health implications of depression and cognitive impairment in
      late life are enormous. Cognitive impairment and late-life depression are
      associated with increased risk for subsequent dementia; however, investigations
      of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND
      DATA SOURCE: The National Institute of Mental Health organized the conference
      "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to
      consider how the varied perspectives might be better integrated to examine the
      associations among depression, mild cognitive impairment, and cognitive decline
      and to illuminate the common or distinct mechanisms involved in these
      associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1)
      What gaps in our knowledge have the greatest public health significance? (2) Can
      we more efficiently use our research dollars and participant resources to fill
      these gaps? Meeting participants included grantees from the National Institute of
      Mental Health and the National Institute on Aging and program staff from the
      National Institute of Mental Health, the National Institute on Aging, and the
      National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the
      most important recommendations to emerge from the meeting discussions is for
      increased collaboration among clinical and epidemiological investigators whose
      work focuses in the area of depression with those working primarily in the area
      of memory disorders. Directions for future research were identified.

PMID- 16461856
TI  - Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a
      magnetic resonance imaging study of chronic schizophrenia, first-episode
      psychosis, and ultra-high-risk individuals.
AB  - CONTEXT: Magnetic resonance imaging studies have identified hippocampal volume
      reductions in schizophrenia and amygdala volume enlargements in bipolar disorder,
      suggesting different medial temporal lobe abnormalities in these conditions.
      These studies have been limited by small samples and the absence of patients
      early in the course of illness. OBJECTIVE: To investigate hippocampal and
      amygdala volumes in a large sample of patients with chronic schizophrenia,
      patients with first-episode psychosis, and patients at ultra-high risk for
      psychosis compared with control subjects. DESIGN: Cross-sectional comparison
      between patient groups and controls. SETTING: Individuals with chronic
      schizophrenia were recruited from a mental health rehabilitation service, and
      individuals with first-episode psychosis and ultra-high risk were recruited from
      the ORYGEN Youth Health Service. Control subjects were recruited from the
      community. PARTICIPANTS: The study population of 473 individuals included 89 with
      chronic schizophrenia, 162 with first-episode psychosis, 135 at ultra-high risk
      for psychosis (of whom 39 subsequently developed a psychotic illness), and 87
      controls. MAIN OUTCOME MEASURES: Hippocampal, amygdala, whole-brain, and
      intracranial volumes were estimated on high-resolution magnetic resonance images
      and compared across groups, including first-episode subgroups. We used 1- and 2
      way analysis of variance designs to compare hippocampal and amygdala volumes
      across groups, correcting for intracranial volume and covarying for age and sex.
      We investigated the effects of medication and illness duration on structural
      volumes. RESULTS: Patients with chronic schizophrenia displayed bilateral
      hippocampal volume reduction. Patients with first-episode schizophrenia but not
      schizophreniform psychosis displayed left hippocampal volume reduction. The
      remaining first-episode subgroups had normal hippocampal volumes compared with
      controls. Amygdala volume enlargement was identified only in first-episode
      patients with nonschizophrenic psychoses. Patients at ultra-high risk for
      psychosis had normal baseline hippocampal and amygdala volumes whether or not
      they subsequently developed a psychotic illness. Structural volumes did not
      differ between patients taking atypical vs typical antipsychotic medications, and
      they remained unchanged when patients treated with lithium were excluded from the
      analysis. CONCLUSIONS: Medial temporal structural changes are not seen until
      after the onset of a psychotic illness, and the pattern of structural change
      differs according to the type of psychosis. These findings have important
      implications for future neurobiological studies of psychotic disorders and
      emphasize the importance of longitudinal studies examining patients before and
      after the onset of a psychotic illness.

PMID- 16461857
TI  - Depressive symptoms and cognitive decline in late life: a prospective
      epidemiological study.
AB  - CONTEXT: Depression is associated with cognitive impairment and dementia. It is
      less clear whether depression contributes to further cognitive decline over time,
      independently of incipient dementia. OBJECTIVE: To examine the relationship
      between depressive symptoms and subsequent cognitive decline in a cohort of
      nondemented older adults, some of whom remained dementia free during follow-up
      and others in whom incident dementia eventually developed. DESIGN: Twelve-year
      prospective epidemiological study, including biennial measurement of cognition
      and depressive symptoms, biennial assessment of dementia, and comparison of
      cognitive function at baseline and over time in persons with and without baseline
      depressive symptoms in the dementia-free and eventual-dementia groups, using
      random-effects models. SETTING: A largely blue-collar rural community.
      PARTICIPANTS: Population-based sample of 1265 adults 67 years and older without
      dementia at baseline. MAIN OUTCOME MEASURES: Scores over time on each of several
      cognitive test composites. RESULTS: Among 1094 participants who remained dementia
      free, those with baseline depressive symptoms had significantly lower baseline
      scores on all cognitive composites than the nondepressed participants. Among the
      171 individuals in whom dementia later developed, depression was associated with
      worse performance in some but not all baseline cognitive composites. Cognitive
      decline over time was minimal in the dementia-free group, whereas marked decline
      was seen in the eventual-dementia group. Depressive symptoms were not associated
      with rate of cognitive decline over time in either group. CONCLUSIONS: Depressive
      symptoms are cross-sectionally associated with cognitive impairment but not
      subsequent cognitive decline. Substantial cognitive decline over time cannot be
      explained by depression and most likely reflects incipient dementia.

PMID- 16461859
TI  - Increased hippocampal plaques and tangles in patients with Alzheimer disease with
      a lifetime history of major depression.
AB  - CONTEXT: The hallmark pathological changes in Alzheimer disease (AD) are abundant
      plaque and tangle formation, especially in the temporal lobes and hippocampus.
      Although there is increasing evidence that major depression may interact with
      neuropathological processes in AD, there have been no studies of
      neuropathological changes in AD as a function of history of major depression.
      OBJECTIVE: To test the hypothesis that neuritic plaques and neurofibrillary
      tangles are more pronounced in the hippocampus of patients with AD with a
      lifetime history of major depressive disorder, as compared with patients with AD
      without depression history. DESIGN: Postmortem study. SETTING: Nursing home.
      PARTICIPANTS: The brains of 52 patients with AD without a lifetime history of
      major depression were compared with the brains of 50 patients with AD with a
      lifetime history of major depression. MAIN OUTCOME MEASURES: Neuropathological
      ratings from the Consortium to Establish a Registry in Alzheimer Disease battery.
      RESULTS: Brains of patients with AD with a lifetime history of depression showed
      higher levels of both plaque (P<.005) and tangle (P<.002) formation within the
      hippocampus than brains of patients with AD without a history of depression. Post
      hoc analyses showed that patients with AD who had a history of depression
      exhibited more rapid cognitive decline than patients without a history of
      depression (P<.004). Furthermore, within the group of patients with AD with a
      history of depression, patients who exhibited concurrent depression at the time
      of first diagnosis of AD exhibited more pronounced neuropathological changes in
      the hippocampus (P<.006). CONCLUSIONS: In AD, the presence of a lifetime history
      of depression corresponds to increases in AD-related neuropathological changes
      within the hippocampus. These changes go along with more rapid cognitive decline
      in patients with AD with a history of depression, and are more pronounced in
      patients with AD suffering from depression early on in the disease process,
      suggesting an interaction between major depression and AD neuropathology.

PMID- 16461860
TI  - Role of genes and environments for explaining Alzheimer disease.
AB  - CONTEXT: Twin studies using selected samples have shown high heritability for
      Alzheimer disease (AD). OBJECTIVE: To evaluate genetic and environmental
      influences on AD in a fully ascertained population of older twins, including like
      and unlike-sex pairs. DESIGN: Five-group quantitative genetic model: male
      monozygotic twins, female monozygotic twins, male dizygotic twins, female
      dizygotic twins, and unlike-sex twins. SETTING AND PARTICIPANTS: All twins in the
      Swedish Twin Registry aged 65 years and older. The study included 11,884 twin
      pairs, among whom were 392 pairs in which 1 or both members had AD. MAIN OUTCOME
      MEASURES: All individuals were screened for cognitive dysfunction. Suspected
      cases of dementia and their co-twins received complete clinical diagnostic
      evaluations for AD. Estimates of heritability, shared environmental influences,
      and nonshared environmental influences, adjusting for age, were derived from the
      twin data. RESULTS: Heritability for AD was estimated to be 58% in the full model
      and 79% in the best-fitting model, with the balance of variation explained by
      nonshared environmental influences. There were no significant differences between
      men and women in prevalence or heritability after controlling for age. Within
      pairs concordant for AD, intrapair difference in age at onset was significantly
      greater in dizygotic than in monozygotic pairs, suggesting genetic influences on
      timing of the disease. CONCLUSIONS: In the largest twin study to date, we
      confirmed that heritability for AD is high and that the same genetic factors are
      influential for both men and women. However, nongenetic risk factors also play an
      important role and might be the focus for interventions to reduce disease risk or
      delay disease onset.

PMID- 16461862
TI  - Corticolimbic blood flow during nontraumatic emotional processing in
      posttraumatic stress disorder.
AB  - CONTEXT: Recent brain imaging studies implicate dysfunction of limbic and
      paralimbic circuitry, including the amygdala and medial prefrontal cortex (MPFC),
      in the pathogenesis of posttraumatic stress disorder (PTSD) during traumatic
      recollection and imagery. However, the relationship between activity in these
      regions and general emotional processing unrelated to traumatic experience has
      not been fully examined. OBJECTIVE: To investigate activity in the limbic and
      paralimbic brain regions in PTSD in response to a challenge with emotionally
      salient generic visual images. DESIGN: Cross-sectional, case-control study.
      SETTING: Academic medical center. PARTICIPANTS: Sixteen Vietnam veterans with
      combat-related PTSD (PTSD group), 15 combat-exposed Vietnam veterans without PTSD
      (combat control group), and 15 age- and sex-matched healthy controls (normal
      control group). MAIN OUTCOME MEASURES: We used positron emission tomography to
      study regional cerebral blood flow while participants viewed complex visual
      pictures with negatively valenced/aversive, nonaversive ("neutral"), and blank
      pictures. Psychophysiologic and emotional self-report data were also recorded.
      RESULTS: All 3 groups activated the dorsal MPFC to general salient content.
      Controls without PTSD activated the left amygdala in response to aversive
      stimuli. Normal controls activated the ventral MPFC and combat-exposed non-PTSD
      and PTSD participants exhibited either no response or deactivation in these
      regions, respectively, during negative emotional experience. CONCLUSIONS:
      Consistent with current functional neuroanatomic models, patients with PTSD
      exhibited altered neural responses in the amygdala and ventral MPFC during the
      processing of emotionally salient but trauma-unrelated stimuli, potentially
      reflecting disorder-specific changes. Activation of the amygdala and lack of
      ventral MPFC deactivation to negatively valenced images in combat controls may
      reflect compensatory changes after trauma exposure that are not associated with
      PTSD.

PMID- 16461861
TI  - Clinical course of children and adolescents with bipolar spectrum disorders.
AB  - CONTEXT: Despite the high morbidity associated with bipolar disorder (BP), few
      studies have prospectively studied the course of this illness in youth.
      OBJECTIVE: To assess the longitudinal course of BP spectrum disorders (BP-I, BP
      II, and not otherwise specified [BP-NOS]) in children and adolescents. DESIGN:
      Subjects were interviewed, on average, every 9 months for an average of 2 years
      using the Longitudinal Interval Follow-up Evaluation. SETTING: Outpatient and
      inpatient units at 3 university centers. PARTICIPANTS: Two hundred sixty-three
      children and adolescents (mean age, 13 years) with BP-I (n = 152), BP-II (n =
      19), and BP-NOS (n = 92). MAIN OUTCOME MEASURES: Rates of recovery and
      recurrence, weeks with syndromal or subsyndromal mood symptoms, changes in
      symptoms and polarity, and predictors of outcome. RESULTS: Approximately 70% of
      subjects with BP recovered from their index episode, and 50% had at least 1
      syndromal recurrence, particularly depressive episodes. Analyses of weekly mood
      symptoms showed that 60% of the follow-up time, subjects had syndromal or
      subsyndromal symptoms with numerous changes in symptoms and shifts of polarity,
      and 3% of the time, psychosis. Twenty percent of BP-II subjects converted to BP
      I, and 25% of BP-NOS subjects converted to BP-I or BP-II. Early-onset BP, BP-NOS,
      long duration of mood symptoms, low socioeconomic status, and psychosis were
      associated with poorer outcomes and rapid mood changes. Secondary analyses
      comparing BP-I youths with BP-I adults showed that youths significantly more time
      symptomatic and had more mixed/cycling episodes, mood symptom changes, and
      polarity switches. CONCLUSIONS: Youths with BP spectrum disorders showed a
      continuum of BP symptom severity from subsyndromal to full syndromal with
      frequent mood fluctuations. Results of this study provide preliminary validation
      for BP-NOS.

PMID- 16461863
TI  - Physical and mental health costs of traumatic war experiences among Civil War
      veterans.
AB  - BACKGROUND: Hundreds of thousands of soldiers face exposure to combat during wars
      across the globe. The health effects of traumatic war experiences have not been
      adequately assessed across the lifetime of these veterans. OBJECTIVE: To identify
      the role of traumatic war experiences in predicting postwar nervous and physical
      disease and mortality using archival data from military and medical records of
      veterans from the Civil War. DESIGN: An archival examination of military and
      medical records of Civil War veterans was conducted. Degree of trauma experienced
      (prisoner-of-war experience, percentage of company killed, being wounded, and
      early age at enlistment), signs of lifetime physician-diagnosed disease, and age
      at death were recorded. SETTING AND PARTICIPANTS: The US Pension Board surgeons
      conducted standardized medical examinations of Civil War veterans over their
      postwar lifetimes. Military records of 17,700 Civil War veterans were matched to
      postwar medical records. MAIN OUTCOME MEASURES: Signs of physician-diagnosed
      disease, including cardiac, gastrointestinal, and nervous disease; number of
      unique ailments within each disease; and mortality. RESULTS: Military trauma was
      related to signs of disease and mortality. A greater percentage of company killed
      was associated with signs of postwar cardiac and gastrointestinal disease
      (incidence risk ratio [IRR], 1.34; P < .02), comorbid nervous and physical
      disease (IRR, 1.51; P < .005), and more unique ailments within each disease (IRR,
      1.14; P < .005). Younger soldiers (<18 years), compared with older enlistees (>30
      years), showed a higher mortality risk (hazard ratio, 1.52), signs of comorbid
      nervous and physical disease (IRR, 1.93), and more unique ailments within each
      disease (IRR, 1.32) (P < .005 for all), controlling for time lived and other
      covariates. CONCLUSIONS: Greater exposure to death of military comrades and
      younger exposure to war trauma were associated with increased signs of physician
      diagnosed cardiac, gastrointestinal, and nervous disease and more unique disease
      ailments across the life of Civil War veterans. Physiological mechanisms by which
      trauma might result in disease are discussed.

PMID- 16461864
TI  - Effects of lower-cost incentives on stimulant abstinence in methadone maintenance
      treatment: a National Drug Abuse Treatment Clinical Trials Network study.
AB  - BACKGROUND: Contingency management interventions that provide tangible incentives
      based on objective indicators of drug abstinence have improved treatment outcomes
      of substance abusers, but have not been widely implemented in community drug
      abuse treatment settings. OBJECTIVE: To compare outcomes achieved when a lower
      cost prize-based contingency management treatment is added to usual care in
      community methadone hydrochloride maintenance treatment settings. DESIGN: Random
      assignment to usual care with (n = 198) or without (n = 190) abstinence
      incentives during a 12-week trial. SETTING: Six community-based methadone
      maintenance drug abuse treatment clinics in locations across the United States.
      PARTICIPANTS: Three hundred eighty-eight stimulant-abusing patients enrolled in
      methadone maintenance programs for at least 1 month and no more than 3 years.
      INTERVENTION: Participants submitting stimulant- and alcohol-negative samples
      earned draws for a chance to win prizes; the number of draws earned increased
      with continuous abstinence time. MAIN OUTCOME MEASURES: Total number of stimulant
      and alcohol-negative samples provided, percentage of stimulant- and alcohol
      negative samples provided, longest duration of abstinence, retention, and
      counseling attendance. RESULTS: Submission of stimulant- and alcohol-negative
      samples was twice as likely for incentive as for usual care group participants
      (odds ratio, 1.98; 95% confidence interval, 1.42-2.77). Achieving 4 or more, 8 or
      more, and 12 weeks of continuous abstinence was approximately 3, 9, and 11 times
      more likely, respectively, for incentive vs usual care participants. Groups did
      not differ on study retention or counseling attendance. The average cost of
      prizes was 120 dollars per participant. CONCLUSION: An abstinence incentive
      approach that paid 120 dollars in prizes per participant effectively increased
      stimulant abstinence in community-based methadone maintenance treatment clinics.

PMID- 16461866
TI  - Six-month trial of bupropion with contingency management for cocaine dependence
      in a methadone-maintained population.
AB  - CONTEXT: No effective pharmacotherapies exist for cocaine dependence, although
      contingency management (CM) has demonstrated efficacy. OBJECTIVE: To compare the
      efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone
      hydrochloride-maintained individuals. DESIGN: This 25-week, placebo-controlled,
      double-blind trial randomly assigned participants to 1 of 4 treatment conditions:
      CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher
      control and placebo (VCP), or voucher control and bupropion (VCB). SETTING:
      Outpatient clinic at the Veterans Affairs Connecticut Healthcare System.
      PARTICIPANTS: A total of 106 opiate-dependent, cocaine-abusing individuals.
      INTERVENTIONS: All study participants received methadone hydrochloride (range, 60
      120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d
      beginning at week 3. In the CM conditions, each urine sample negative for both
      opioids and cocaine resulted in a monetary-based voucher that increased for
      consecutively drug-free urine samples during weeks 1 to 13. Completion of
      abstinence-related activities also resulted in a voucher. During weeks 14 to 25,
      only completion of activities was reinforced in the CM group, regardless of
      sample results. The voucher control groups received vouchers for submitting urine
      samples, regardless of results, throughout the study. MAIN OUTCOME MEASURE:
      Thrice-weekly urine toxicologic test results for cocaine and heroin. RESULTS:
      Groups did not differ in baseline characteristics or retention rates. Opiate use
      decreased significantly, with all treatment groups attaining equivalent amounts
      of opiate use at the end of the study. In the CMB group, the proportion of
      cocaine-positive samples significantly decreased during weeks 3 to 13 (P<.001)
      relative to week 3 and remained low during weeks 14 to 25. In the CMP group,
      cocaine use significantly increased during weeks 3 to 13 (P<.001) relative to
      week 3, but then cocaine use significantly decreased relative to the initial
      slope during weeks 14 to 25 (P<.001). In contrast, by treatment end, the VCB and
      VCP groups showed no significant improvement in cocaine use. CONCLUSION: These
      findings suggest that combining CM with bupropion for the treatment of cocaine
      addiction may significantly improve outcomes relative to bupropion alone.

PMID- 16461867
TI  - Randomized controlled trial of a primary care and home-based intervention for
      physical activity and nutrition behaviors: PACE+ for adolescents.
AB  - OBJECTIVE: Many adolescents do not meet national guidelines for participation in
      regular moderate or vigorous physical activity (PA); limitations on sedentary
      behaviors; or dietary intake of fruits and vegetables, fiber, or total dietary
      fat. This study evaluated a health care-based intervention to improve these
      behaviors. DESIGN: Randomized controlled trial. SETTING: Primary care with follow
      up at home. PARTICIPANTS: Eight hundred seventy-eight adolescent girls and boys
      aged 11 to 15 years. INTERVENTIONS: Two experimental conditions: (1) Primary
      care, office-based, computer-assisted diet and PA assessment and stage-based goal
      setting followed by brief health care provider counseling and 12 months of
      monthly mail and telephone counseling and (2) a comparison condition addressing
      sun exposure protection. MAIN OUTCOME MEASURES: Minutes per week of moderate plus
      vigorous PA measured by self-report and accelerometer; self-report of days per
      week of PA and sedentary behaviors; and percentage of energy from fat and
      servings per day of fruits and vegetables measured by three 24-hour diet recalls.
      Body mass index (calculated as weight in kilograms divided by the square of
      height in meters) was a secondary outcome. RESULTS: Compared with adolescents in
      the sun protection condition, girls and boys in the diet and PA intervention
      significantly reduced sedentary behaviors (intervention vs control change, 4.3 to
      3.4 h/d vs 4.2 to 4.4 h/d for girls, respectively [P = .001]; 4.2 to 3.2 h/d vs
      4.2 to 4.3 h/d for boys, respectively [P = .001]). Boys reported more active days
      per week (intervention vs control change: 4.1 to 4.4 d/wk vs 3.8 to 3.8 d/w,
      respectively [P = .01]), and the number of servings of fruits and vegetables for
      girls approached significance (intervention vs control change, 3.5 to 4.2
      servings/d vs 3.5 to 3.9 servings/d, respectively [P = .07]). No intervention
      effects were seen with percentage of calories from fat or minutes of PA per week.
      Percentage of adolescents meeting recommended health guidelines was significantly
      improved for girls for consumption of saturated fat (intervention vs control
      change, 23.4% to 41.0% vs 18.5% to 31%, respectively [relative risk, 1.33; 95%
      confidence interval, 1.01-1.68]) and for boys' participation in d/wk of PA
      (intervention vs control change, 45.3% to 55.4% vs 41.9% to 38.0%, respectively
      [relative risk, 1.47; 95% confidence interval, 1.19-1.75]). No between-group
      differences were seen in body mass index. CONCLUSIONS: Improvements in some diet,
      PA, and sedentary behaviors in adolescents can be enabled through the use of a 1
      year, integrated intervention using the computer, health provider counseling,
      mail, and telephone. The amount of intervention received may contribute to its
      efficacy.

PMID- 16461865
TI  - Injectable, sustained-release naltrexone for the treatment of opioid dependence:
      a randomized, placebo-controlled trial.
AB  - CONTEXT: Oral naltrexone can completely antagonize the effects produced by opioid
      agonists. However, poor compliance with naltrexone has been a major obstacle to
      the effective treatment of opioid dependence. OBJECTIVE: To evaluate the safety
      and efficacy of a sustained-release depot formulation of naltrexone in treating
      opioid dependence. DESIGN AND SETTING: Randomized, double-blind, placebo
      controlled, 8-week trial conducted at 2 medical centers. PARTICIPANTS: Sixty
      heroin-dependent adults. INTERVENTIONS: Participants were stratified by sex and
      years of heroin use (> or = 5 vs < 5) and then were randomized to receive placebo
      or 192 or 384 mg of depot naltrexone. Doses were administered at the beginning of
      weeks 1 and 5. All participants received twice-weekly relapse prevention therapy,
      provided observed urine samples, and completed other assessments at each visit.
      MAIN OUTCOME MEASURES: Retention in treatment and percentage of opioid-negative
      urine samples. RESULTS: Retention in treatment was dose related, with 39%, 60%,
      and 68% of patients in the placebo, 192 mg of naltrexone, and 384 mg of
      naltrexone groups, respectively, remaining in treatment at the end of 2 months.
      Time to dropout had a significant main effect of dose, with mean time to dropout
      of 27, 36, and 48 days for the placebo, 192 mg of naltrexone, and 384 mg of
      naltrexone groups, respectively. The percentage of urine samples negative for
      opioids, methadone, cocaine, benzodiazepines, and amphetamine varied
      significantly as a function of dose. When the data were recalculated without the
      assumption that missing urine samples were positive, a main effect of group was
      not found for any drugs tested except cocaine, where the percentage of cocaine
      negative urine samples was lower in the placebo group. Adverse events were
      minimal and generally mild. This formulation of naltrexone was well tolerated and
      produced a robust, dose-related increase in treatment retention. CONCLUSION:
      These data provide new evidence of the feasibility, efficacy, and tolerability of
      long-lasting antagonist treatments for opioid dependence.

PMID- 16461868
TI  - Prevalence of the female athlete triad syndrome among high school athletes.
AB  - OBJECTIVE: To estimate the prevalence of the female athlete triad (disordered
      eating, menstrual irregularity, and low bone mass) among high school athletes.
      DESIGN: Observational cross-sectional study. SETTING: High school. PARTICIPANTS:
      Female athletes (n= 170) representing 8 sports were recruited from 6 high schools
      in southern California. MAIN OUTCOME MEASURES: Disordered eating and menstrual
      status were determined by interviewer-assisted questionnaires. Bone mineral
      density was measured by dual-energy x-ray absorptiometry of the hip, spine (L1
      L4), and total body. RESULTS: Among all athletes, 18.2%, 23.5%, and 21.8% met the
      criteria for disordered eating, menstrual irregularity, and low bone mass,
      respectively. Ten girls (5.9%) met criteria for 2 components of the triad, and 2
      girls (1.2%) met criteria for all 3 components. Oligomenorrheic/amenorrheic
      athletes had higher mean +/- SD eating restraint (1.55 +/- 1.60 vs 1.04 +/- 1.27;
      P = .02) and Eating Disorder Examination Questionnaire global scores (1.68 +/-
      1.20 vs 1.33 +/- 1.14; P = .03) than eumenorrheic athletes. After controlling for
      age, age at menarche, body mass index, race/ethnicity, and sport type, athletes
      with oligomenorrhea/amenorrhea had significantly lower mean +/- SD bone mineral
      densities for the trochanter (0.884 +/- 0.090 g . cm(-2)) than eumenorrheic
      athletes (0.933 +/- 0.130 g . cm(-2); P = .04). CONCLUSIONS: The prevalence of
      the full female athlete triad was low in our sample; however, a substantial
      percentage of the athletes may be at risk for long-term health consequences
      associated with disordered eating, menstrual irregularity, or low bone mass.
      Preparticipation screening to identify these components should be encouraged as a
      preventive approach to identify high-risk athletes.

PMID- 16461869
TI  - Drug testing of adolescents in ambulatory medicine: physician practices and
      knowledge.
AB  - OBJECTIVE: To determine physicians' knowledge of urine drug testing and usual
      practices when performing drug testing on adolescent patients at a time when
      interest in drug testing of adolescents is on the rise and physicians may be
      consulted for advice and requests to perform tests. DESIGN AND PARTICIPANTS:
      Multimodal survey conducted April to July 2004 consisting of 42 forced-choice
      response items. Participants were practicing physicians randomly selected from
      the national membership rolls of the American Academy of Pediatrics, Society of
      Adolescent Medicine, and American Academy of Family Physicians who provided care
      for 10 or more adolescents per week. We computed simple frequencies and sample
      design-adjusted 95% confidence intervals for each item. RESULTS: The survey was
      completed by 359 eligible physicians (response rate, 42%). More than 95% of
      respondents had ever ordered urine drug tests. Only 23% used an effective urine
      sample collection procedure, and only 7% used specific gravity and measurement of
      urine creatinine level to ensure validity of the sample, as recommended. When
      asked which drugs can be detected in routine panels, only 10% answered all items
      correctly, 47% did not know for 1 or more items, and 75% responded incorrectly
      for 1 or more items. CONCLUSIONS: Primary care physicians do not always use
      proper urine sample collection and validation procedures, and they are not aware
      of important limitations of drug testing. The primary care workforce is not
      prepared to assist with drug testing programs. Physicians who order these tests
      need more training and access to consultation with experts.

PMID- 16461871
TI  - Effect of telephone reminder/recall on adolescent immunization and preventive
      visits: results from a randomized clinical trial.
AB  - OBJECTIVE: To measure the effect of telephone-based reminder/recall on
      immunization and well-child care (WCC) visit rates among adolescents in urban
      practices. DESIGN: Randomized clinical trial of telephone-based reminder/recall
      over 18 months. SETTING: Four urban primary care practices. PARTICIPANTS:
      Adolescents aged 11 to 14 years.Intervention Adolescents within practices were
      randomized to study (n = 1496) or control groups (n = 1510). The study group was
      sent audiotaped telephone reminders about a scheduled or needed immunization or
      WCC visit. Households were called weekly if there was no response; telephone
      numbers were updated weekly. Controls received standard care. RESULTS: Baseline
      demographics and immunization and WCC visit rates were similar for study and
      control groups. The intervention was largely ineffective in improving
      immunization or WCC visit rates. Although at the end of the study, the study
      group had slightly higher hepatitis B coverage (3 vaccinations) (62% vs 57.8%; P
      = .02), WCC visits were the same (53% and 54%), and impact on other vaccinations
      was minimal. The effect of reminder/recall was equivalent across demographic
      subgroups (e.g., age, race/ethnicity, insurance). The major factor limiting
      intervention effectiveness was inaccurate telephone numbers. Seventy-one percent
      of study subjects with single telephone numbers throughout the study had a WCC
      visit vs 25% of study subjects with multiple/changed telephone numbers and 54% of
      controls (P<.001). CONCLUSIONS: An intensive telephone reminder and recall system
      was only minimally successful in improving immunization and WCC visit rates among
      urban adolescents. Lack of success was largely owing to changed or inaccurate
      telephone numbers.

PMID- 16461870
TI  - Association of condom use, sexual behaviors, and sexually transmitted infections
      with the duration of genital human papillomavirus infection among adolescent
      women.
AB  - OBJECTIVE: To examine the association of potentially modifiable factors such as
      condom use, sexual behaviors, and concurrent sexually transmitted infections with
      duration of genital human papillomavirus (HPV) infections among adolescent women.
      DESIGN: Longitudinal observational study. SETTING: Study conducted at 3 inner
      city clinics in Indianapolis, Ind. PARTICIPANTS: Forty-nine HPV-positive
      adolescents were tested frequently for HPV infection and provided sexual behavior
      diaries. Main Exposures Condom use, sexual behaviors, number of partners, and
      concurrent infections with Neisseria gonorrhoeae, Chlamydia trachomatis, and
      Trichomonas vaginalis. MAIN OUTCOME MEASURES: Time from onset to clearance of
      type-specific HPV infections was analyzed with proportional hazard models.
      Adjusted hazard ratios (AHRs) were used to assess the effects of risk factors on
      the duration of HPV infection. Because viral clearance is a preferred outcome, a
      variable with an AHR less than 1 was considered a risk factor (ie, associated
      with reduced chance of viral clearance and prolonged infection). RESULTS:
      Prolonged HPV infection was associated with oncogenic HPV types (AHR, 0.58 [95%
      confidence interval (CI), 0.39-0.84]) less than median level of condom use during
      an HPV infection (AHR, 0.53 [95% CI, 0.33-0.84]) and coinfection with C
      trachomatis (AHR, 0.58 [95% CI, 0.31-0.89]) or T vaginalis (AHR, 0.32 [95% CI,
      0.16-0.64]). Not having multiple sexual partners during an HPV infection was
      associated with early HPV clearance (AHR, 5.52 [95% CI, 3.28-9.30]). CONCLUSIONS:
      These findings support public health messages of reducing the number of sexual
      partners, promoting routine condom use, and frequent sexually transmitted
      infection screening that may be beneficial with HPV infections.

PMID- 16461872
TI  - Simulating cost-effectiveness of fluoride varnish during well-child visits for
      Medicaid-enrolled children.
AB  - OBJECTIVE: To examine the cost-effectiveness of fluoride varnish application by
      medical providers when implemented within a well-child periodicity schedule for
      Medicaid-enrolled children. DESIGN: Cost-effectiveness was analyzed using
      published probabilities and costs. Input parameters included the effectiveness of
      fluoride varnish (35.4%) applied according to the well-child periodicity schedule
      up to 3 years of age at $16.00 per application, annual caries increment (14%),
      age-specific dental care usage rates (0.2% at 9 months to 19% at 42 months), and
      age-related nonhospital treatment costs ($292.00-$503.00) and hospital treatment
      costs ($2191.00-$2940.00). Sensitivity analysis was conducted to assess the
      effects for varying input parameters. SETTING: Well-child visits during primary
      care. PARTICIPANTS: Children aged 9 to 42 months. INTERVENTION: Application of
      universal fluoride varnish (fluoride varnish-all) at 9, 18, 24, and 36 months vs
      no intervention (fluoride varnish-none) was compared. MAIN OUTCOME MEASURES: Cost
      per month without cavities and treatment averted during the first 42 months of
      life from a Medicaid payer's perspective. RESULTS: Fluoride varnish improved
      clinical outcomes by 1.52 cavity-free months but at a cost of $7.18 for each
      cavity-free month gained per child and $203 for each treatment averted.
      Considerable uncertainty existed for some parameters. Fluoride varnish was cost
      saving when dental services and nonhospital treatment costs were 1.5 to 2 times
      greater, respectively, than our base case estimate. CONCLUSIONS: Based on these
      assumptions, fluoride varnish use in the medical setting is effective in reducing
      early childhood caries in low-income populations but is not cost saving in the
      first 42 months of life. Potential total cost reductions with varying parameters
      suggest that evaluations using a longitudinal cohort are needed.

PMID- 16461873
TI  - Neonatal abstinence syndrome after in utero exposure to selective serotonin
      reuptake inhibitors in term infants.
AB  - OBJECTIVE: To compare the prevalence and clinical characteristics of neonatal
      abstinence syndrome in neonates exposed and not exposed to selective serotonin
      reuptake inhibitors (SSRIs) in utero. DESIGN: Cohort study. SETTING: Tertiary
      care center. Patients One hundred twenty term infants, of whom 60 had prolonged
      in utero exposure to SSRIs, including paroxetine hydrochloride, fluoxetine,
      citalopram hydrobromide, sertraline hydrochloride, and venlafaxine hydrochloride.
      MAIN OUTCOME MEASURES: Neonatal abstinence syndrome was assessed with the
      Finnegan score as follows: score of 8 or above, severe; score of 4 to 7, mild;
      and score of 0 to 3, normal. All infants were followed up with a standardized
      protocol that included repeated Finnegan score assessments and cardiorespiratory
      monitoring until normalization of the Finnegan score. RESULTS: Of the 60 neonates
      exposed to SSRIs in utero, 8 showed severe and 10 showed mild symptoms of a
      neonatal abstinence syndrome. All nonexposed neonates had a normal Finnegan
      score. In neonates who developed severe symptoms, the maximum mean daily Finnegan
      scores were recorded within 2 days after birth, although maximum individual
      scores were recorded as long as 4 days after birth. CONCLUSIONS: Neonatal
      abstinence syndrome occurs in 30% of neonates exposed to SSRIs in utero. These
      neonates should be monitored for at least 48 hours after birth. The long-term
      effects of prolonged exposure to SSRIs, particularly in neonates who develop
      severe symptoms, have yet to be determined.

PMID- 16461874
TI  - Access to health care for young adults with disabling chronic conditions.
AB  - OBJECTIVE: To assess health insurance status and health care access of young
      adults with disabilities attributable to a chronic condition. DESIGN AND SETTING:
      We analyzed data from the National Health Interview Survey from 1999 to 2002. We
      present bivariate analysis and multiple logistic regression of reported health
      care access barriers in the United States stratified by health insurance status.
      PARTICIPANTS: The study population included 1109 survey respondents with and 22
      481 without disabling chronic conditions, aged 19 to 29 years. MAIN OUTCOME
      MEASURES: Delayed or unmet health needs owing to cost, no contact with a health
      professional in the prior year, and no usual source of care. RESULTS: Thirty-five
      percent of respondents with and 15% without disabling chronic conditions reported
      an unmet health care need owing to cost (P< .001). Uninsurance rates for young
      adults with and without disabling chronic conditions were similar (26% vs 28%,
      respectively), and uninsurance was significantly associated with unmet health
      care needs. More than two thirds of uninsured respondents with a disabling
      chronic condition reported an unmet health need and 45% reported no usual source
      of care. After adjusting for sociodemographic factors, uninsured young adults
      with disabling chronic conditions had 8 times greater odds of reporting unmet
      health care needs and 6 times greater odds of having no usual source of care
      relative to insured respondents with disabling chronic conditions. CONCLUSIONS:
      Despite increasing attention to issues of health care transition for young adults
      with disabling chronic conditions, this study suggests that uninsurance is as
      common among these young adults as nondisabled peers and is significantly
      associated with health care access barriers in this population.

PMID- 16461875
TI  - Developmental status and service use among children in the child welfare system:
      a national survey.
AB  - OBJECTIVES: To estimate the prevalence of developmental delay and service use
      among children in the child welfare system and to identify factors that influence
      these outcomes. DESIGN: A descriptive study using wave 1 of the National Survey
      of Child and Adolescent Well-Being. PARTICIPANTS AND SETTING: Children aged 0 to
      10 years (n = 4324) and their caregivers were interviewed within 60 days of a
      report being made to the child welfare system. Children's development was
      measured directly using standardized assessment tools. Three questions from the
      caregiver interviews estimated receipt of developmental services. MAIN EXPOSURES:
      Subjects were characterized as having developmental delay if any developmental
      measure fell more than 2 SDs below the mean. Prevalence of developmental delay
      and service use by age group, type of maltreatment, type of placement, race, sex,
      and income were reported. Odds that children aged 0 to 2, 3 to 5, and 6 to 10
      years with developmental delay would receive developmental services were
      calculated using weighted logistic regression. main outcome measure: Receipt of
      developmental services by children with developmental delay. RESULTS: Younger
      children aged 0 to 2 and 3 to 5 years had higher rates, 33% and 36%,
      respectively, of developmental delay than school-aged children (13%) (P<.01).
      Despite their high prevalence of developmental delay, children aged 0 to 2 years
      were less likely to receive developmental services than preschool-aged children
      (odds ratio, 2.4; 95% confidence interval, 1.6-3.7) or school-aged children (odds
      ratio, 4.2; 95% confidence interval, 2.9-6.0). CONCLUSIONS: Rates of
      developmental delay are high and developmental services are underused,
      particularly by young children in the child welfare system. Strategies for
      overcoming barriers to using early intervention services should be implemented.

PMID- 16461876
TI  - Picture of the month. Neonatal lupus erythematosus.

PMID- 16461877
TI  - A successful international child health elective: the University of Colorado
      Department of Pediatrics' experience.
AB  - OBJECTIVES: To describe the organizational features of an international child
      health elective (ICHE) and to document the diversity of diagnoses observed by
      residents. DESIGN: Faculty from the Department of Pediatrics, University of
      Colorado Health Sciences Center, Denver, created a steering committee in 1999 to
      develop and direct an ICHE, including selecting residents, selecting and
      organizing sites, and creating objectives and a year-long preparatory curriculum.
      The elective was piloted in 2000 and repeated in 2002 and 2004. SETTING AND
      PARTICIPANTS: Residents chose from 4 ICHE sites in Peru and Guatemala, where they
      observed clinical care in various clinical settings during a 4-week elective.
      MAIN OUTCOME MEASURES: The ICHE was evaluated via written evaluations by faculty
      and residents as well as written and oral reports by participating residents.
      RESULTS: During the 2000 and 2004 electives, residents recorded clinical cases in
      a data-entry log. Of the patients logged, 18% had illnesses never seen before by
      the residents and 5.6% had illnesses in advanced stages not previously seen by
      the residents. Strong reciprocal relationships were created between the
      department and participating international institutions. Residents reported
      uniformly that the elective was a valuable element of their training.
      CONCLUSIONS: Planning and faculty involvement in ICHEs helps to ensure
      achievement of elective objectives. Well-organized ICHEs have the potential to
      augment resident education. The experience at our institution demonstrates that
      ICHEs can provide experience with a variety of medical systems, exposure to
      diverse pathophysiologic conditions, and opportunities for collaboration with
      international colleagues.

PMID- 16461878
TI  - Antipyretic treatment in young children with fever: acetaminophen, ibuprofen, or
      both alternating in a randomized, double-blind study.
AB  - OBJECTIVE: To compare the antipyretic benefit of acetaminophen or ibuprofen
      monotherapy with an alternating regimen of both drugs in young children aged 6 to
      36 months. DESIGN: Randomized, double-blind, parallel-group trial. SETTING: Three
      primary pediatric community ambulatory centers in central Israel. PARTICIPANTS: A
      total of 464 children aged 6 to 36 months with fever. INTERVENTION: Infants were
      assigned to receive either acetaminophen (12.5 mg/kg per dose every 6 hours) (n =
      154) or ibuprofen (5 mg/kg per dose every 8 hours) (n = 155) or to receive
      alternating acetaminophen and ibuprofen (every 4 hours) (n = 155) for 3 days
      after a loading dose. MAIN OUTCOME MEASURES: Temperature, stress score, amount of
      antipyretic received, total days that the infant or caregiver was absent from day
      care or work, respectively, at the 3-day time point, recurrence of fever, and
      number of emergency department visits. RESULTS: The group given the alternating
      regimen was characterized by a lower mean temperature, more rapid reduction of
      fever, receiving less antipyretic medication, less stress, and less absenteeism
      from day care as compared with the other groups; all of the differences were
      statistically significant (P< .001). None of the regimens were associated with a
      significantly higher number of emergency department visits (P = .65) or serious
      long-term complications (P = .66). The drug used for initial loading had no
      effect on outcome in any of the groups. CONCLUSIONS: An alternating treatment
      regimen of acetaminophen (12.5 mg/kg per dose) and ibuprofen (5 mg/kg per dose)
      every 4 hours for 3 days, regardless of the initial loading medication, is more
      effective than monotherapy in lowering fever in infants and children.

PMID- 16461879
TI  - Variation of cognition and achievement with sleep-disordered breathing in full
      term and preterm children.
AB  - OBJECTIVE: Pediatric sleep-disordered breathing (SDB) has a disproportionately
      high prevalence in children who were preterm infants (preterm children) and is
      associated with behavioral comorbidity. Exposure to intermittent hypoxemia and
      sleep disruption may contribute to cognitive impairment. We quantified the
      association of SDB with cognition and achievement and determined whether preterm
      children are at a differentially increased risk for SDB-related impairments.
      DESIGN: Cross-sectional analyses. SETTING: Urban community. PARTICIPANTS: Eight
      hundred thirty-five children, aged 8 to 11 years.Intervention(s) None. MAIN
      OUTCOME MEASURES: Scores on the Peabody Picture Vocabulary Test-Revised, Kaufman
      Assessment Battery for Children, and Continuous Performance Test. RESULTS: One
      hundred sixty-four children had SDB. In unadjusted analyses, children with SDB
      had poorer scores on almost all tests of cognition and achievement. Group
      differences were attenuated after adjusting for socioeconomic status; in these
      analyses, children with SDB scored lower on the Peabody Picture Vocabulary Test
      Revised (mean +/- SE score, 100.5 +/- 1.4 vs 103.6 +/- 0.7; P = .04), and the
      Kaufman Assessment Battery for Children riddles and triangles subscales.
      Associations were stronger in preterm than in full-term children. Of the sleep
      measures, snoring history was most strongly correlated with indices of cognition
      and achievement. CONCLUSIONS: Although moderate group differences were observed
      for almost all cognitive measures, an attenuation of effects was observed once
      socioeconomic status was considered. The deficits in selective measures of
      academic abilities, language comprehension, and planning and organizational
      skills suggest a negative impact of SDB on achievement and cognition. Stronger
      associations in preterm children suggest the importance of screening for snoring,
      a good predictor of cognitive function in this population.

PMID- 16461880
TI  - Effect on hospital-wide sedation practices after implementation of the 2001 JCAHO
      procedural sedation and analgesia guidelines.
AB  - OBJECTIVE: To describe the effect of implementing the Joint Commission on
      Accreditation of Healthcare Organization's guidelines for procedural sedation and
      analgesia (PSA) on the frequency of adverse events occurring during sedation.
      DESIGN: Prospective, descriptive study. SETTING: Urban, tertiary care children's
      hospital. PARTICIPANTS: Patients requiring PSA. INTERVENTIONS: A PSA committee
      and a standardized protocol for PSA were developed during a 6-month period.
      Institutional oversight was initiated to monitor practitioner compliance with the
      program. Data were abstracted from the sedation record. MAIN OUTCOME MEASURES:
      The change in incidence of adverse events during PSA during the study. The
      strength of the association was determined by computing the Pearson product
      moment correlation. RESULTS: A total of 14 386 patients received PSA between July
      1, 2001, and June 30, 2004. During the study, 7.6% of patients had an adverse
      event, with the most common being hypoxemia (39.7% of all adverse events). A
      trend toward a decrease in the incidence of adverse events was found during the
      study (Pearson product moment correlation, -0.68; P<.001). CONCLUSIONS:
      Implementation of the 2001 Joint Commission on Accreditation of Healthcare
      Organizations guidelines for the provision of PSA appeared to lead to a decrease
      in the incidence of adverse events during the study. Implementation of uniform
      standards of monitoring and care for the provision of PSA may lead to safer
      conditions for pediatric patients undergoing PSA.

PMID- 16461881
TI  - Obesity prevention in primary care.

PMID- 16461882
TI  - If you don't ask, parents may not tell: noticing problems vs expressing concerns.

PMID- 16461883
TI  - Application of sequence-based methods in human microbial ecology.
AB  - Ecologists studying microbial life in the environment have recognized the
      enormous complexity of microbial diversity for many years, and the development of
      a variety of culture-independent methods, many of them coupled with high
      throughput DNA sequencing, has allowed this diversity to be explored in ever
      greater detail. Despite the widespread application of these new techniques to the
      characterization of uncultivated microbes and microbial communities in the
      environment, their application to human health and disease has lagged. Because
      DNA-based techniques for defining uncultured microbes allow not only cataloging
      of microbial diversity but also insight into microbial functions, investigators
      are beginning to apply these tools to the microbial communities that abound on
      and within us, in what has aptly been called "the second Human Genome Project."
      In this review we discuss the sequence-based methods for microbial analysis that
      are currently available and their application to identify novel human pathogens,
      improve diagnosis of known infectious diseases, and advance understanding of our
      relationship with microbial communities that normally reside in and on the human
      body.

PMID- 16461885
TI  - Making a virtue out of a necessity: hurricanes and the resilience of community
      organization.

PMID- 16461884
TI  - Dynamic evolution at pericentromeres.
AB  - Pericentromeres are exceptional genomic regions: in animals they contain
      extensive segmental duplications implicated in gene creation, and in plants they
      sustain rearrangements and insertions uncommon in euchromatin. To examine the
      mechanisms and patterns of plant pericentromere evolution, we compared
      pericentromere sequence from four Brassicaceae species separated by <15 million
      years (Myr). This flowering plant family is ideal for studying relationships
      between genome reorganization and pericentromere evolution-its members have
      undergone recent polyploidization and hybridization, with close relatives
      changing in genome size and chromosome number. Through sequence and hybridization
      analyses, we examined regions from Arabidopsis arenosa, Capsella rubella, and
      Olimarabidopsis pumila that are homologous to Arabidopsis thaliana
      pericentromeres (peri-CENs) III and V, and used FISH to demonstrate they have
      been maintained near centromere satellite arrays in each species. Sequence
      analysis revealed a set of highly conserved genes, yet we discovered substantial
      differences in intergenic length and species-specific changes in sequence content
      and gene density. We discovered that A. thaliana has undergone recent,
      significant expansions within its pericentromeres, in some cases measuring
      hundreds of kilobases; these findings are in marked contrast to euchromatic
      segments in these species that exhibit only minor length changes. While plant
      pericentromeres do contain some duplications, we did not find evidence of
      extensive segmental duplications, as has been documented in primates. Our data
      support a model in which plant pericentromeres may experience selective pressures
      distinct from euchromatin, tolerating rapid, dynamic changes in structure and
      sequence content, including large insertions of mobile elements, 5S rDNA arrays
      and pseudogenes.

PMID- 16461886
TI  - Standing guard: Perinuclear localization of an RNA-dependent RNA polymerase.

PMID- 16461887
TI  - Hutchinson-Gilford progeria mutant lamin A primarily targets human vascular cells
      as detected by an anti-Lamin A G608G antibody.
AB  - Hutchinson-Gilford progeria syndrome (HGPS; Online Mendelian Inheritance in Man
      accession no. 176670) is a rare disorder that is characterized by segmental
      premature aging and death between 7 and 20 years of age from severe premature
      atherosclerosis. Mutations in the LMNA gene are responsible for this syndrome.
      Approximately 80% of HGPS cases are caused by a G608 (GGC-->GGT) mutation within
      exon 11 of LMNA, which elicits a deletion of 50 aa near the C terminus of
      prelamin A. In this article, we present evidence that the mutant lamin A
      (progerin) accumulates in the nucleus in a cellular age-dependent manner. In
      human HGPS fibroblast cultures, we observed, concomitantly to nuclear progerin
      accumulation, severe nuclear envelope deformations and invaginations preventable
      by farnesyltransferase inhibition. Nuclear alterations affect cell-cycle
      progression and cell migration and elicit premature senescence. Strikingly, skin
      biopsy sections from a subject with HGPS showed that the truncated lamin A
      accumulates primarily in the nuclei of vascular cells. This finding suggests that
      accumulation of progerin is directly involved in vascular disease in progeria.

PMID- 16461888
TI  - Nanomechanics of the subtectorial space caused by electromechanics of cochlear
      outer hair cells.
AB  - The stereocilia of the cochlear inner hair cells (IHCs) transduce vibrations into
      the sensory receptor current. Until now, mechanisms for deflecting these
      stereocilia have not been identified experimentally. Here, we identify a
      mechanism by using the electromechanical properties of the soma of the outer hair
      cell to produce an intracochlear, mechanical force stimulus. It is known that the
      soma of this cell generates mechanical force in response to a change of its
      transmembrane potential. In the present experiments, the force was induced by
      intracochlear electrical stimulation at frequencies that covered the entire
      functionally relevant range of 50 kHz. Vibration responses were measured in the
      transverse direction with a laser Doppler vibrometer. For frequencies up to
      approximately 3 kHz in the first three turns of the guinea-pig cochlea, the
      apical surface of the IHC and the opposing surface of the tectorial membrane were
      found to vibrate with similar amplitudes but opposite phases. At high
      frequencies, there was little relative motion between these surfaces in the
      transverse direction. The counterphasic motion up to approximately 3 kHz results
      in a pulsatile motion of the fluid surrounding the stereocilia of the IHCs. Based
      on physical principles of fluid flow between narrowly spaced elastic plates, we
      show that radial fluid motion is amplified relative to transverse membrane motion
      and that the radial motion is capable of bending the stereocilia. In conclusion,
      for frequencies up to at least 3 kHz, there appears to be direct fluid coupling
      between outer hair cells and IHCs.

PMID- 16461889
TI  - Fast complementation of split fluorescent protein triggered by DNA hybridization.
AB  - Fluorescent proteins have proven to be excellent reporters and biochemical
      sensors with a wide range of applications. In a split form, they are not
      fluorescent, but their fluorescence can be restored by supplementary protein
      protein or protein-nucleic acid interactions that reassemble the split
      polypeptides. However, in prior studies, it took hours to restore the
      fluorescence of a split fluorescent protein because the formation of the protein
      chromophore slowly occurred de novo concurrently with reassembly. Here we provide
      evidence that a fluorogenic chromophore can self-catalytically form within an
      isolated N-terminal fragment of the enhanced green fluorescent protein (EGFP). We
      show that restoration of the split protein fluorescence can be driven by nucleic
      acid complementary interactions. In our assay, fluorescence development is fast
      (within a few minutes) when complementary oligonucleotide-linked fragments of the
      split EGFP are combined. The ability of our EGFP system to respond quickly to DNA
      hybridization should be useful for detecting the kinetics of many other types of
      pairwise interactions both in vitro and in living cells.

PMID- 16461890
TI  - Profile of Isaac M. Held.

PMID- 16461891
TI  - Lateral mobility of proteins in liquid membranes revisited.
AB  - The biological function of transmembrane proteins is closely related to their
      insertion, which has most often been studied through their lateral mobility. For
      >30 years, it has been thought that hardly any information on the size of the
      diffusing object can be extracted from such experiments. Indeed, the hydrodynamic
      model developed by Saffman and Delbruck predicts a weak, logarithmic dependence
      of the diffusion coefficient D with the radius R of the protein. Despite
      widespread use, its validity has never been thoroughly investigated. To check
      this model, we measured the diffusion coefficients of various peptides and
      transmembrane proteins, incorporated into giant unilamellar vesicles of 1
      stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) or in model bilayers of
      tunable thickness. We show in this work that, for several integral proteins
      spanning a large range of sizes, the diffusion coefficient is strongly linked to
      the protein dimensions. A heuristic model results in a Stokes-like expression for
      D, (D proportional, variant 1/R), which fits literature data as well as ours.
      Diffusion measurement is then a fast and fruitful method; it allows determining
      the oligomerization degree of proteins or studying lipid-protein and protein
      protein interactions within bilayers.

PMID- 16461892
TI  - Controlling the shape, orientation, and linkage of carbon nanotube features with
      nano affinity templates.
AB  - Directed assembly of nanoscale building blocks such as single-walled carbon
      nanotubes (SWNTs) into desired architectures is a major hurdle for a broad range
      of basic research and technological applications (e.g., electronic devices and
      sensors). Here we demonstrate a parallel assembly process that allows one to
      simultaneously position, shape, and link SWNTs with sub-100-nm resolution. Our
      method is based on the observation that SWNTs are strongly attracted to COOH
      terminated self-assembled monolayers (COOH-SAMs) and that SWNTs with lengths
      greater than the dimensions of a COOH-SAM feature will align along the boundary
      between the COOH-SAM feature and a passivating CH3-terminated SAM. By using
      nanopatterned affinity templates of 16-mercaptohexadecanonic acid, passivated
      with 1-octadecanethiol, we have formed SWNT dot, ring, arc, letter, and even more
      sophisticated structured thin films and continuous ropes. Experiment and theory
      (Monte Carlo simulations) suggest that the COOH-SAMs localize the solvent
      carrying the nanotubes on the SAM features, and that van der Waals interactions
      between the tubes and the COOH-rich feature drive the assembly process. A
      mathematical relationship describing the geometrically weighted interactions
      between SWNTs and the two different SAMs required to overcome solvent-SWNT
      interactions and effect assembly is provided.

PMID- 16461893
TI  - Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1
      (MKP-1) in innate immune responses.
AB  - Engagement of Toll-like receptors (TLRs) on macrophages leads to activation of
      the mitogen-activated protein kinases (MAPKs), which contribute to innate immune
      responses. MAPK activity is regulated negatively by MAPK phosphatases (MKPs). MKP
      1, the founding member of this family of dual-specificity phosphatases, has been
      implicated in regulating lipopolysaccharide (LPS) responses, but its role in TLR
      mediated immune responses in vivo has not been defined. Here, we show that mice
      deficient in MKP-1 were highly susceptible to endotoxic shock in vivo, associated
      with enhanced production of proinflammatory cytokines TNF-alpha and IL-6 and an
      anti-inflammatory cytokine, IL-10. We further examined the regulation and
      function of MKP-1 in macrophages, a major cell type involved in endotoxic shock.
      MKP-1 was transiently induced by TLR stimulation through pathways mediated by
      both myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor
      inducing IFN-beta (TRIF). MKP-1 deficiency led to sustained activation of p38
      MAPK and c-Jun N-terminal kinase (JNK) in LPS-treated macrophages. In response to
      TLR signals, MKP-1-deficient macrophages produced 5- to 10-fold higher IL-10,
      which could be blocked by a p38 MAPK inhibitor. Thus, p38 MAPK plays a critical
      role in mediating IL-10 synthesis in TLR signaling. TNF-alpha was found to be
      more abundant in MKP-1-deficient macrophages within 2 hours of TLR stimulation,
      but its production was rapidly down-regulated by IL-10. Our studies demonstrate
      that MKP-1 attenuates the activities of p38 MAPK and JNK to regulate both pro-
      and anti-inflammatory cytokines in TLR signaling. These results highlight the
      complex mechanisms by which the MAPKs regulate innate immunity.

PMID- 16461894
TI  - Cardiac-specific overexpression of sarcolipin in phospholamban null mice impairs
      myocyte function that is restored by phosphorylation.
AB  - Sarcolipin (SLN) inhibits the cardiac sarco(endo)plasmic reticulum Ca2+ ATPase
      (SERCA2a) by direct binding and is superinhibitory if it binds as a binary
      complex with phospholamban (PLN). To demonstrate whether overexpression of SLN in
      the heart might impair cardiac function directly, transgenic (TG) mice with
      cardiac-specific overexpression of NF-SLN (SLN tagged at its N terminus with the
      FLAG epitope) were generated on a phospholamban (PLN) null (PLN KO) background.
      In NF-SLN TG/PLN KO cardiac microsomes, the apparent affinity of SERCA2a for Ca2+
      was decreased compared with non-TG littermate PLN KO hearts. Analyses of isolated
      NF-SLN/PLN KO cardiomyocytes revealed impaired cardiac contractility, reduced
      calcium transient peak amplitude, and slower decay kinetics compared to PLN KO
      animals. In these cardiomyocytes, isoproterenol restored calcium dynamics to the
      levels seen in PLN KO. Invasive hemodynamic and echocardiographic analyses of NF
      SLN/PLN KO mouse cardiac muscle in vivo showed no direct effects of NF-SLN
      overexpression when compared to PLN KO mice. A possible mechanism for the lack of
      effects in the whole heart may be a responsiveness to phosphorylation because we
      determined that NF-SLN can be phosphorylated in cardiomyocytes in response to
      isoproterenol, and we provide evidence that serine/threonine kinase 16 is a
      kinase that can phosphorylate NF-SLN. Site-directed mutagenesis showed that SLN
      Thr-5 is the target site for this kinase. These data show that overexpression of
      NF-SLN can inhibit SERCA2a in the absence of PLN and that the inhibition of
      SERCA2a is correlated with impairment of contractility and calcium cycling in
      cardiomyocytes.

PMID- 16461895
TI  - Reprogramming of replicative senescence in hepatocellular carcinoma-derived
      cells.
AB  - Tumor cells have the capacity to proliferate indefinitely that is qualified as
      replicative immortality. This ability contrasts with the intrinsic control of the
      number of cell divisions in human somatic tissues by a mechanism called
      replicative senescence. Replicative immortality is acquired by inactivation of
      p53 and p16INK4a genes and reactivation of hTERT gene expression. It is unknown
      whether the cancer cell replicative immortality is reversible. Here, we show the
      spontaneous induction of replicative senescence in p53-and p16INK4a-deficient
      hepatocellular carcinoma cells. This phenomenon is characterized with hTERT
      repression, telomere shortening, senescence arrest, and tumor suppression. SIP1
      gene (ZFHX1B) is partly responsible for replicative senescence, because short
      hairpin RNA-mediated SIP1 inactivation released hTERT repression and rescued
      clonal hepatocellular carcinoma cells from senescence arrest.

PMID- 16461897
TI  - The unique cytoarchitecture of human pancreatic islets has implications for islet
      cell function.
AB  - The cytoarchitecture of human islets has been examined, focusing on cellular
      associations that provide the anatomical framework for paracrine interactions. By
      using confocal microscopy and multiple immunofluorescence, we found that,
      contrary to descriptions of prototypical islets in textbooks and in the
      literature, human islets did not show anatomical subdivisions. Insulin
      immunoreactive beta cells, glucagon-immunoreactive alpha cells, and somatostatin
      containing delta cells were found scattered throughout the human islet. Human
      beta cells were not clustered, and most (71%) showed associations with other
      endocrine cells, suggesting unique paracrine interactions in human islets. Human
      islets contained proportionally fewer beta cells and more alpha cells than did
      mouse islets. In human islets, most beta, alpha, and delta cells were aligned
      along blood vessels with no particular order or arrangement, indicating that
      islet microcirculation likely does not determine the order of paracrine
      interactions. We further investigated whether the unique human islet
      cytoarchitecture had functional implications. Applying imaging of cytoplasmic
      free Ca2+ concentration, [Ca2+]i, we found that beta cell oscillatory activity
      was not coordinated throughout the human islet as it was in mouse islets.
      Furthermore, human islets responded with an increase in [Ca2+]i when lowering the
      glucose concentration to 1 mM, which can be attributed to the large contribution
      of alpha cells to the islet composition. We conclude that the unique cellular
      arrangement of human islets has functional implications for islet cell function.

PMID- 16461896
TI  - Retinoic acid regulates sex-specific timing of meiotic initiation in mice.
AB  - In mammals, meiosis is initiated at different time points in males and females,
      but the mechanism underlying this difference is unknown. Female germ cells begin
      meiosis during embryogenesis. In males, embryonic germ cells undergo G0/G1
      mitotic cell cycle arrest, and meiosis begins after birth. In mice, the
      Stimulated by Retinoic Acid Gene 8 (Stra8) has been found to be required for the
      transition into meiosis in both female and male germ cells. Stra8 is expressed in
      embryonic ovaries just before meiotic initiation, whereas its expression in
      testes is first detected after birth. Here we examine the mechanism underlying
      the sex-specific timing of Stra8 expression and meiotic initiation in mice. Our
      work shows that signaling by retinoic acid (RA), an active derivative of vitamin
      A, is required for Stra8 expression and thereby meiotic initiation in embryonic
      ovaries. We also discovered that RA is sufficient to induce Stra8 expression in
      embryonic testes and in vitamin A-deficient adult testes in vivo. Finally, our
      results show that cytochrome p450 (CYP)-mediated RA metabolism prevents premature
      Stra8 expression in embryonic testes. Treatment with an inhibitor specific to RA
      metabolizing enzymes indicates that a cytochrome p450 from the 26 family (CYP26)
      is responsible for delaying Stra8 expression in embryonic testes. Sex-specific
      regulation of RA signaling thus plays an essential role in meiotic initiation in
      embryonic ovaries and precludes its occurrence in embryonic testes. Because RA
      signaling regulates Stra8 expression in both embryonic ovaries and adult testes,
      this portion of the meiotic initiation pathway may be identical in both sexes.

PMID- 16461898
TI  - Evolution of enzymes in a series is driven by dissimilar functional demands.
AB  - That distinct enzyme activities in an unbranched metabolic pathway are
      evolutionarily tuned to a single functional requirement is a pervasive
      assumption. Here we test this assumption by examining the activities of two
      consecutively acting enzymes in human erythrocytes with an approach to
      quantitative evolutionary design that avoids the above-mentioned assumption. We
      previously found that avoidance of NADPH depletion during the pulses of oxidative
      load to which erythrocytes are normally exposed is the main functional
      requirement mediating selection for high glucose-6-phosphate dehydrogenase
      activity. In the present study, we find that, in contrast, the maintenance of
      oxidized glutathione at low concentrations is the main functional requirement
      mediating selection for high glutathione reductase activity. The results in this
      case show that, contrary to the assumption of a single functional requirement,
      natural selection for the normal activities of the distinct enzymes in the
      pathway is mediated by different requirements. On the other hand, the results
      agree with the more general principles that underlie our approach. Namely, that
      (i) the values of biochemical parameters evolve so as to fulfill the various
      performance requirements that are relevant to achieve high fitness, and (ii)
      these performance requirements can be inferred from quantitative systems theory
      considerations, informed by knowledge of specific aspects of the biochemistry,
      physiology, genetics, and ecology of the organism.

PMID- 16461899
TI  - Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in
      cultured human hepatoma cells.
AB  - Infections with hepatitis C virus (HCV) are marked by frequent viral persistence,
      chronic liver disease, and extraordinary viral genetic diversity. Although much
      has been learned about HCV since its discovery, progress has been slowed by a
      lack of permissive cell culture systems supporting its replication. Productive
      infections have been achieved recently with genotype 2a virus, but cirrhosis and
      liver cancer are typically associated with genotype 1 HCV, which is more
      prevalent and relatively resistant to IFN therapy. We describe production of
      infectious genotype 1a HCV in cells transfected with synthetic RNA derived from a
      prototype virus (H77-S). Viral proteins accumulated more slowly in H77-S
      transfected cells than in cells transfected with genotype 2a (JFH-1) RNA, but
      substantially more H77-S RNA was secreted into supernatant fluids. Most secreted
      RNA was noninfectious, banding in isopycnic gradients at a density of 1.04-1.07
      gm/cm(3), but infectivity was associated with H77-S particles possessing a
      density of 1.13-1.14 gm/cm(3). The specific infectivity of H77-S particles (5.4 x
      10(4) RNA copies per focus-forming unit) was significantly lower than JFH-1 virus
      (1.4 x 10(2) RNA copies per focus-forming unit). Infection with either virus was
      blocked by CD81 antibody. Sera from genotype 1a-infected individuals neutralized
      H77-S virus, but had little activity against genotype 2a virus, suggesting that
      these genotypes represent different serotypes. The ability of this genotype 1a
      virus to infect cultured cells will substantially benefit antiviral and vaccine
      discovery programs.

PMID- 16461900
TI  - The glycophorin C N-linked glycan is a critical component of the ligand for the
      Plasmodium falciparum erythrocyte receptor BAEBL.
AB  - Plasmodium vivax uses a single member of the Duffy binding-like (DBL) receptor
      family to invade erythrocytes and is not found in West Africa where its
      erythrocyte ligand, the Duffy blood group antigen, is missing. In contrast,
      Plasmodium falciparum expresses four members of the DBL family, and remarkably,
      single-point mutations of two of these receptors (BAEBL and JESEBL) bind to
      entirely different erythrocyte ligands, greatly expanding the range of
      erythrocytes that P. falciparum can invade. In this article, we describe the
      molecular basis of the binding specificity for one BAEBL variant (VSTK) that
      binds to glycophorin C. We demonstrate that soluble glycophorin C completely
      blocks the binding of BAEBL (VSTK) to human erythrocytes, requiring 0.7 microM
      for 50% inhibition, a concentration similar to that required by glycophorin A to
      block the binding of erythrocyte-binding antigen 175 to erythrocytes. BAEBL
      (VSTK) does not bind to Gerbich-negative erythrocytes that express a truncated
      form of glycophorin C because it lacks exon 3. The N-linked oligosaccharide of
      Gerbich-negative glycophorin C has a markedly different composition than the wild
      type glycophorin C. Moreover, removal of the N-linked oligosaccharide from the
      wild-type glycophorin C eliminates its ability to inhibit binding of BAEBL (VSTK)
      to erythrocytes. These findings are consistent with the ligand for BAEBL (VSTK)
      being, in part, the N-linked oligosaccharide and suggest that single-point
      mutations in BAEBL allow P. falciparum to recognize oligosaccharides on different
      erythrocyte surface glycoproteins or glycolipids, greatly increasing its invasion
      range.

PMID- 16461901
TI  - In vivo repopulation ability of genetically corrected bone marrow cells from
      Fanconi anemia patients.
AB  - Fanconi anemia (FA) is a rare inherited genomic instability syndrome representing
      one of the best examples of hematopoietic stem cell deficiency. Although FA might
      be an excellent candidate for bone marrow (BM) genetic correction ex vivo,
      knockout animal models are not sufficient to guide preclinical steps, and gene
      therapy attempts have proven disappointing so far. Contributing to these poor
      results is a characteristic and dramatic early BM-cells die-off when placed in
      culture. We show here that human primary FA BM cell survival can be ameliorated
      by using specific culture conditions that limit oxidative stress. When coupled
      with retrovirus-mediated transfer of the main complementation group FANCA-cDNA,
      we could achieve long-term reconstitution of the stem cell compartment both in
      vitro and in vivo. Gene-corrected BM cultures grew for >120 days, and after
      cultured cell transplantation into NOD/SCID mice, clonogenic human cells carrying
      the FANCA transgene could be detected 6 months after transduction. By comparison,
      untransduced cells died in culture by 15 days. Of necessity for ethical reasons,
      experiments were conducted on a very limited number of primary BM cells. By using
      low cytokine regimen and conditions matching regulatory requirements, a
      contingent of gene-corrected cells slowly emerges with an unmet potential for in
      vivo engraftment. Future therapeutic applications of stem cells might be
      expanding from these data. In addition, we provide a model of gene-corrected
      human primary cell growth that carries the potential to better delineate the
      combined role of both DNA damage and oxidative stress in the pathogenesis of FA.

PMID- 16461902
TI  - Malaria risk on the Amazon frontier.
AB  - Frontier malaria is a biological, ecological, and sociodemographic phenomenon
      operating over time at three spatial scales (micro/individual, community, and
      state and national). We explicate these linkages by integrating data from remote
      sensing surveys, ground-level surveys and ethnographic appraisal, focusing on the
      Machadinho settlement project in Rondonia, Brazil. Spatially explicit analyses
      reveal that the early stages of frontier settlement are dominated by
      environmental risks, consequential to ecosystem transformations that promote
      larval habitats of Anopheles darlingi. With the advance of forest clearance and
      the establishment of agriculture, ranching, and urban development, malaria
      transmission is substantially reduced, and risks of new infection are largely
      driven by human behavioral factors. Malaria mitigation strategies for frontier
      settlements require a combination of preventive and curative methods and close
      collaboration between the health and agricultural sectors. Of fundamental
      importance is matching the agricultural potential of specific plots to the
      economic and technical capacities of new migrants. Equally important is providing
      an effective agricultural extension service.

PMID- 16461903
TI  - Role of positive selection in the retention of duplicate genes in mammalian
      genomes.
AB  - The question of how duplicate genes are retained in a population remains
      controversial. The duplication-degeneration-complementation model, which involves
      no positive selection, stipulates a higher retention rate of duplicate genes in a
      small population than in a large one. This model has been accepted by many
      evolutionists. However, we found considerably more retentions and fewer losses of
      duplicate genes in the mouse genome than in the human genome, although the
      population size of rodents is in general larger than that of primates. Indeed, in
      nearly every interval of synonymous divergence between duplicate genes, the
      number of gene retentions in mouse is larger than that in human. Our findings
      suggest a more important role of positive selection in duplicate retention than
      duplication-degeneration-complementation. In addition, certain functional
      categories show a higher tendency of lineage-specific expansion than expected,
      suggesting lineage-specific selection or functional bias in retained duplicates.

PMID- 16461904
TI  - The brain differentiates human and non-human grammars: functional localization
      and structural connectivity.
AB  - The human language faculty has been claimed to be grounded in the ability to
      process hierarchically structured sequences. This human ability goes beyond the
      capacity to process sequences with simple transitional probabilities of adjacent
      elements observable in non-human primates. Here we show that the processing of
      these two sequence types is supported by different areas in the human brain.
      Processing of local transitions is subserved by the left frontal operculum, a
      region that is phylogenetically older than Broca's area, which specifically holds
      responsible the computation of hierarchical dependencies. Tractography data
      revealing differential structural connectivity signatures for these two brain
      areas provide additional evidence for a segregation of two areas in the left
      inferior frontal cortex.

PMID- 16461905
TI  - Combinatorial Gata2 and Sca1 expression defines hematopoietic stem cells in the
      bone marrow niche.
AB  - The interaction between stem cells and their supportive microenvironment is
      critical for their maintenance, function, and survival. Whereas hematopoietic
      stem cells (HSCs) are among the best characterized of tissue stem cells, their
      precise site of residence (referred to as the niche) in the adult bone marrow has
      not been precisely defined. In this study, we found that a Gata2 promoter directs
      activity in all HSCs. We show that HSCs can be isolated efficiently from bone
      marrow cells by following Gata2-directed GFP fluorescence, and that they can also
      be monitored in vivo. Each individual GFP-positive cell lay in a G0/G1 cell cycle
      state, in intimate contact with osteoblasts beside the endosteum, at the edge of
      the bone marrow. We conclude that the HSC niche is composed of solitary cells and
      that adult bone marrow HSC are not clustered.

PMID- 16461906
TI  - SAD-2 is required for meiotic silencing by unpaired DNA and perinuclear
      localization of SAD-1 RNA-directed RNA polymerase.
AB  - A gene unpaired during the meiotic homolog pairing stage in Neurospora generates
      a sequence-specific signal that silences the expression of all copies of that
      gene. This process is called Meiotic Silencing by Unpaired DNA (MSUD).
      Previously, we have shown that SAD-1, an RNA-directed RNA polymerase (RdRP), is
      required for MSUD. We isolated a second gene involved in this process, sad-2.
      Mutated Sad-2 (RIP) alleles, like those of Sad-1, are dominant and suppress MSUD.
      Crosses homozygous for Sad-2 are blocked at meiotic prophase. SAD-2 colocalizes
      with SAD-1 in the perinuclear region, where small interfering RNAs have been
      shown to reside in mammalian cells. A functional sad-2(+) gene is necessary for
      SAD-1 localization, but the converse is not true. The data suggest that SAD-2 may
      function to recruit SAD-1 to the perinuclear region, and that the proper
      localization of SAD-1 is important for its activity.

PMID- 16461907
TI  - Amplification of MET may identify a subset of cancers with extreme sensitivity to
      the selective tyrosine kinase inhibitor PHA-665752.
AB  - The success of molecular targeted therapy in cancer may depend on the selection
      of appropriate tumor types whose survival depends on the drug target, so-called
      "oncogene addiction." Preclinical approaches to defining drug-responsive subsets
      are needed if initial clinical trials are to be directed at the most susceptible
      patient population. Here, we show that gastric cancer cells with high-level
      stable chromosomal amplification of the growth factor receptor MET are
      extraordinarily susceptible to the selective inhibitor PHA-665752. Although MET
      activation has primarily been linked with tumor cell migration and invasiveness,
      the amplified wild-type MET in these cells is constitutively activated, and its
      continued signaling is required for cell survival. Treatment with PHA-665752
      triggers massive apoptosis in 5 of 5 gastric cancer cell lines with MET
      amplification but in 0 of 12 without increased gene copy numbers (P = 0.00016).
      MET amplification may thus identify a subset of epithelial cancers that are
      uniquely sensitive to disruption of this pathway and define a patient group that
      is appropriate for clinical trials of targeted therapy using MET inhibitors.

PMID- 16461908
TI  - Adipocyte enhancer-binding protein 1 is a potential novel atherogenic factor
      involved in macrophage cholesterol homeostasis and inflammation.
AB  - Peroxisome proliferator-activated receptor gamma1 (PPARgamma1) and liver X
      receptor alpha (LXRalpha) play pivotal roles in macrophage cholesterol
      homeostasis and inflammation, key biological processes in atherogenesis. Herein
      we identify adipocyte enhancer-binding protein 1 (AEBP1) as a transcriptional
      repressor that impedes macrophage cholesterol efflux, promoting foam cell
      formation, via PPARgamma1 and LXRalpha down-regulation. Contrary to AEBP1
      deficiency, AEBP1 overexpression in macrophages is accompanied by decreased
      expression of PPARgamma1, LXRalpha, and their target genes ATP-binding cassette
      A1, ATP-binding cassette G1, apolipoprotein E, and CD36, with concomitant
      elevation in IL-6, TNF-alpha, monocyte chemoattractant protein 1, and inducible
      NO synthase levels. AEBP1, but not the C-terminally truncated DNA-binding domain
      mutant (AEBP1DeltaSty), represses PPARgamma1 and LXRalpha in vitro. Expectedly,
      AEBP1-overexpressing transgenic (AEBP1TG) macrophages accumulate considerable
      amounts of lipids compared with AEBP1 nontransgenic macrophages, making them
      precursors for foam cells. Indeed, AEBP1-overexpressing transgenic macrophages
      exhibit diminished cholesterol efflux compared with AEBP1 nontransgenic
      macrophages, whereas AEBP1-knockout (AEBP1-/-) macrophages exhibit enhanced
      cholesterol efflux compared with wild-type (AEBP1+/+) macrophages. Our in vitro
      and ex vivo experimental data strongly suggest that AEBP1 plays critical
      regulatory roles in macrophage cholesterol homeostasis, foam cell formation, and
      proinflammation. Thereby, we speculate that AEBP1 may be critically implicated in
      the development of atherosclerosis, and it may serve as a molecular target toward
      developing antiinflammatory, antiatherogenic therapeutic approaches.

PMID- 16461909
TI  - 13C isotopologue perturbation studies of Listeria monocytogenes carbon metabolism
      and its modulation by the virulence regulator PrfA.
AB  - The carbon metabolism of Listeria monocytogenes (Lm) EGD and the two isogenic
      mutant strains LmDeltaprfA and LmDeltaprfApPRFA* (showing no or enhanced
      expression, respectively, of the virulence factor PrfA) was determined by 13C
      isotopologue perturbation. After growth of the bacteria in a defined medium
      containing a mixture of [U-13C6]glucose and glucose with natural 13C abundance
      (1:25, wt/wt), 14 amino acids were isolated and analyzed by NMR spectroscopy.
      Multiply 13C-labeled isotopologues were determined quantitatively by signal
      deconvolution. The 13C enrichments and isotopologue patterns allowed the
      reconstruction of most amino acid biosynthesis pathways and illustrated that
      overproduced PrfA may strongly influence the synthesis of some amino acids,
      notably that of the branched amino acids (Val, Ile, and Leu). Retrobiosynthetic
      analysis of the isotopologue compositions showed that degradation of glucose
      occurs to a large extent via the pentose phosphate pathway and that the citrate
      cycle is incomplete because of the absence of 2-oxoglutarate dehydrogenase
      activity. The reconstructed labeling pattern of oxaloacetate indicated its
      formation by carboxylation of pyruvate. This metabolic reaction seems to have a
      strong impact on the growth requirement in defined minimal medium.
      Bioinformatical steady-state network analyses and flux distribution predictions
      confirmed the experimental data and predicted metabolite fluxes through the
      enzymes of the pathways under study.

PMID- 16461910
TI  - Functional dissection of YabA, a negative regulator of DNA replication initiation
      in Bacillus subtilis.
AB  - The regulation of initiation of DNA replication is crucial to ensure that the
      genome is replicated only once per cell cycle. In the Gram-positive bacterium
      Bacillus subtilis, the function of the YabA protein in initiation control was
      assigned based on its interaction with the DnaA initiator and the DnaN sliding
      clamp in the yeast two-hybrid and on the overinitiation phenotype observed in a
      yabA null strain. However, YabA is unrelated to known regulators of initiation
      and interacts with several additional proteins that could also be involved
      directly or not in initiation control. Here, we investigated the specific role of
      YabA interactions with DnaA and DnaN in initiation control by identifying single
      amino acid changes in YabA that disrupted solely the interaction with DnaA or
      DnaN. These disruptive mutations delineated specific interacting surfaces
      involving a Zn2+-cluster structure in YabA. In B. subtilis, these YabA
      interaction mutations abolished both initiation control and the formation of YabA
      foci at the replication factory. Upon coexpression of deficient YabA mutants,
      mixed oligomers formed foci at the replisome and restored initiation control,
      indicating that YabA acts within a heterocomplex with DnaA and DnaN. In
      agreement, purified YabA oligomerized and formed complexes with DnaA and DnaN.
      These findings underscore the functional association of YabA with the replication
      machinery, indicating that YabA regulates initiation through coupling with the
      elongation of replication.

PMID- 16461911
TI  - Simple fold composition and modular architecture of the nuclear pore complex.
AB  - The nuclear pore complex (NPC) consists of multiple copies of approximately 30
      different proteins [nucleoporins (nups)], forming a channel in the nuclear
      envelope that mediates macromolecular transport between the cytosol and the
      nucleus. With <5% of the nup residues currently available in experimentally
      determined structures, little is known about the detailed structure of the NPC.
      Here, we use a combined computational and biochemical approach to assign folds
      for approximately 95% of the residues in the yeast and vertebrate nups. These
      fold assignments suggest an underlying simplicity in the composition and
      modularity in the architecture of all eukaryotic NPCs. The simplicity in NPC
      composition is reflected in the presence of only eight fold types, with the three
      most frequent folds accounting for approximately 85% of the residues. The
      modularity in NPC architecture is reflected in its hierarchical and symmetrical
      organization that partitions the predicted nup folds into three groups: the
      transmembrane group containing transmembrane helices and a cadherin fold, the
      central scaffold group containing beta-propeller and alpha-solenoid folds, and
      the peripheral FG group containing predominantly the FG repeats and the coiled
      coil fold. Moreover, similarities between structures in coated vesicles and those
      in the NPC support our prior hypothesis for their common evolutionary origin in a
      progenitor protocoatomer. The small number of predicted fold types in the NPC and
      their internal symmetries suggest that the bulk of the NPC structure has evolved
      through extensive motif and gene duplication from a simple precursor set of only
      a few proteins.

PMID- 16461913
TI  - Engineering a biospecific communication pathway between cells and electrodes.
AB  - Methods for transducing the cellular activities of mammalian cells into
      measurable electronic signals are important in many biotechnical applications,
      including biosensors, cell arrays, and other cell-based devices. This manuscript
      describes an approach for functionally integrating cellular activities and
      electrical processes in an underlying substrate. The cells are engineered with a
      cell-surface chimeric receptor that presents the nonmammalian enzyme cutinase.
      Action of this cell-surface cutinase on enzyme substrate self-assembled
      monolayers switches a nonelectroactive hydroxyphenyl ester to an electroactive
      hydroquinone, providing an electrical activity that can be identified with cyclic
      voltammetry. In this way, cell-surface enzymatic activity is transduced into
      electronic signals. The development of strategies to directly interface the
      activities of cells with materials will be important to enabling a broad class of
      hybrid microsystems that combine living and nonliving components.

PMID- 16461912
TI  - Cyclin D1b variant influences prostate cancer growth through aberrant androgen
      receptor regulation.
AB  - Cyclin D1 is a multifaceted regulator of both transcription and cell-cycle
      progression that exists in two distinct isoforms, cyclin D1a and D1b. In the
      prostate, cyclin D1a acts through discrete mechanisms to negatively regulate
      androgen receptor (AR) activity and thus limit androgen-dependent proliferation.
      Accordingly, cyclin D1a is rarely overexpressed in prostatic adenocarcinoma and
      holds little prognostic value in this tumor type. However, a common polymorphism
      (A870) known to facilitate production of cyclin D1b is associated with increased
      prostate cancer risk. Here we show that cyclin D1b is expressed at high frequency
      in prostate cancer and is up-regulated in neoplastic disease. Furthermore, our
      data demonstrate that, although cyclin D1b retains AR association, it is
      selectively compromised for AR regulation. The altered ability of cyclin D1b to
      regulate the AR was observed by using both in vitro and in vivo assays and was
      associated with compromised regulation of AR-dependent proliferation. Consistent
      with previous reports, expression of cyclin D1a inhibited cell-cycle progression
      in AR-dependent prostate cancer cells. Strikingly, cyclin D1b significantly
      stimulated proliferation in this cell type. AR-negative prostate cancer cells
      were nonresponsive to cyclin D1 (a or b) expression, indicating that defects in
      AR corepressor function yield a growth advantage specifically in AR-dependent
      cells. In summary, these studies indicate that the altered AR regulatory capacity
      of cyclin D1b contributes to its association with increased prostate cancer risk
      and provide evidence of cyclin D1b-mediated transcriptional regulation.

PMID- 16461914
TI  - Core domain interactions in full-length p53 in solution.
AB  - The tumor suppressor p53 consists of four 393-residue chains, each of which has
      two natively unfolded (N- and C-terminal) and two folded (core and
      tetramerization) domains. Their structural organization is poorly characterized
      as the protein tends to aggregate, has defied crystallization, and is at the
      limits of NMR studies. We first stabilized the protein by mutation to make it
      more suitable for extended study and then acquired NMR spectra on full-length
      protein and various combinations of shorter domain constructs. The NMR spectrum
      (15N,1H transverse relaxation optimized spectroscopy) of full-length p53 was
      close to that expected from the sum of the spectra of isolated individual
      domains. However, patterns of changes in chemical shifts revealed unexpected
      interactions between the core domains. We used the NMR data as constraints in
      docking algorithms and found a previously uncharacterized self-complementary
      surface for the association of core domains into dimers within the tetrameric
      complex. Binding to DNA requires about a 70 degrees rotation to break those
      subunit interactions and form the known protein:protein interface in the p53-DNA
      complex. We verified the interactions by the effects of mutation on DNA binding.
      Spectroscopic, biophysical, and mutational data conspired to give a picture of
      the p53 tetramer as a dimer of loosely tethered core dimers of appropriate
      symmetry to be poised to bind target DNA.

PMID- 16461915
TI  - Appearance of immature/transitional B cells in HIV-infected individuals with
      advanced disease: correlation with increased IL-7.
AB  - Progression of HIV disease is associated with the appearance of numerous B cell
      defects. We describe herein a population of immature/transitional B cells that is
      overly represented in the peripheral blood of individuals with advancing HIV
      disease. These B cells, identified by the expression of CD10, were unresponsive
      by proliferation to B cell receptor triggering and possessed a phenotype and an
      Ig diversity profile that confirmed their immature/transitional stage of
      differentiation. Consistent with an immature status, their lack of proliferation
      to B cell receptor triggering was reversed with CD40 ligand, but not B cell
      activation factor. Finally, levels of CD10 expression on B cells were directly
      correlated with serum levels of IL-7, suggesting that increased levels of IL-7
      modulate human B cell maturation either directly or indirectly by means of a
      homeostatic effect on lymphopenia. Taken together, these data offer insight into
      human B cell development as well as B cell dysfunction in advanced HIV disease
      that may be linked to IL-7-dependent homeostatic events.

PMID- 16461916
TI  - Solution structure of p53 core domain: structural basis for its instability.
AB  - The 25-kDa core domain of the tumor suppressor p53 is inherently unstable and
      melts at just above body temperature, which makes it susceptible to oncogenic
      mutations that inactivate it by lowering its stability. We determined its
      structure in solution using state-of-the-art isotopic labeling techniques and NMR
      spectroscopy to complement its crystal structure. The structure was very similar
      to that in the crystal but far more mobile than expected. Importantly, we were
      able to analyze by NMR the structural environment of several buried polar groups,
      which indicated structural reasons for the instability. NMR spectroscopy, with
      its ability to detect protons, located buried hydroxyl and sulfhydryl groups that
      form suboptimal hydrogen-bond networks. We mutated one such buried pair, Tyr-236
      and Thr-253 to Phe-236 and Ile-253 (as found in the paralogs p63 and p73), and
      stabilized p53 by 1.6 kcal/mol. We also detected differences in the conformation
      of a mobile loop that might reflect the existence of physiologically relevant
      alternative conformations. The effects of temperature on the dynamics of aromatic
      residues indicated that the protein also experiences several dynamic processes
      that might be related to the presence of alternative hydrogen-bond patterns in
      the protein interior. p53 appears to have evolved to be dynamic and unstable.

PMID- 16461918
TI  - Reciprocal actions of REST and a microRNA promote neuronal identity.
AB  - MicroRNAs (miRNAs) are implicated in both tissue differentiation and maintenance
      of tissue identity. In most cases, however, the mechanisms underlying their
      regulation are not known. One brain-specific miRNA, miR-124a, decreases the
      levels of hundreds of nonneuronal transcripts, such that its introduction into
      HeLa cells promotes a neuronal-like mRNA profile. The transcriptional repressor,
      RE1 silencing transcription factor (REST), has a reciprocal activity, inhibiting
      the expression of neuronal genes in nonneuronal cells. Here, we show that REST
      regulates the expression of a family of miRNAs, including brain-specific miR
      124a. In nonneuronal cells and neural progenitors, REST inhibits miR-124a
      expression, allowing the persistence of nonneuronal transcripts. As progenitors
      differentiate into mature neurons, REST leaves miR-124a gene loci, and
      nonneuronal transcripts are degraded selectively. Thus, the combined
      transcriptional and posttranscriptional consequences of REST action maximize the
      contrast between neuronal and nonneuronal cell phenotypes.

PMID- 16461917
TI  - S-nitrosothiol depletion in amyotrophic lateral sclerosis.
AB  - Recent data suggest that either excessive or deficient levels of protein S
      nitrosylation may contribute to disease. Disruption of S-nitrosothiol (SNO)
      homeostasis may result not only from altered nitric oxide (NO) synthase activity
      but also from alterations in the activity of denitrosylases that remove NO
      groups. A subset of patients with familial amyotrophic lateral sclerosis (ALS)
      have mutations in superoxide dismutase 1 (SOD1) that increase the denitrosylase
      activity of SOD1. Here, we show that the increased denitrosylase activity of SOD1
      mutants leads to an aberrant decrease in intracellular protein and peptide S
      nitrosylation in cell and animal models of ALS. Deficient S-nitrosylation is
      particularly prominent in the mitochondria of cells expressing SOD1 mutants. Our
      results suggest that SNO depletion disrupts the function and/or subcellular
      localization of proteins that are regulated by S-nitrosylation such as
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and thereby contributes to ALS
      pathogenesis. Repletion of intracellular SNO levels with SNO donor compounds
      rescues cells from mutant SOD1-induced death. These results suggest that aberrant
      depletion of intracellular SNOs contributes to motor neuron death in ALS, and
      raises the possibility that deficient S-nitrosylation is a general mechanism of
      disease pathogenesis. SNO donor compounds may provide new therapeutic options for
      diseases such as ALS that are associated with deficient S-nitrosylation.

PMID- 16461920
TI  - A transgenic approach for RNA interference-based genetic screening in mice.
AB  - Genetic screening is the most powerful method through which to uncover gene
      function. It has been applied very successfully in lower organisms but seldom
      attempted in mammalian species because of their long generation time. In this
      study, we exploit RNA interference (RNAi) for its potential use in genetic
      screening in mice. We show that RNAi-induced gene knockdown can be generated
      through introducing small hairpin RNA-expressing constructs into the mouse as
      transgenes via conventional pronuclear injection. The knockdown effect can be
      transmitted for many generations in these transgenic animals. In a small-scale
      screening for developmental defects in the kidney, we uncovered a potential role
      of Id4 in the formation of the renal medulla. Our results demonstrate the
      feasibility of using RNAi for genetic screening in mice.

PMID- 16461919
TI  - Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca2+
      and decreased cGMP-induced relaxation.
AB  - Cyclic nucleotides can relax smooth muscle without a change in [Ca2+]i, a
      phenomenon termed Ca2+ desensitization, contributing to vasodilation,
      gastrointestinal motility, and airway resistance. The physiological importance of
      telokin, a 17-kDa smooth muscle-specific protein and target for cyclic nucleotide
      induced Ca2+ desensitization, was determined in telokin null mice bred to a
      congenic background. Telokin null ileal smooth muscle homogenates compared to
      wild type exhibited an approximately 30% decrease in myosin light-chain
      phosphatase (MLCP) activity, which was reflected in a significant leftward shift
      (up to 2-fold at pCa 6.3) of the Ca2+ force relationship accompanied by an
      increase in myosin light-chain phosphorylation. No difference in the Ca2+ force
      relationship occurred in telokin WT and knockout (KO) aortas, presumably
      reflecting the normally approximately 5-fold lower telokin content in aorta vs.
      ileum smooth muscle. Ca2+ desensitization of contractile force by 8-Br-cGMP was
      attenuated by 50% in telokin KO intestinal smooth muscle. The rate of force
      relaxation reflecting MLCP activity, in the presence of 50 microM 8-Br-cGMP, was
      also significantly slowed in telokin KO vs. WT ileum and was rescued by
      recombinant telokin. Normal thick filaments in telokin KO smooth muscles indicate
      that telokin is not required for filament formation or stability. Results
      indicate that a primary role of telokin is to modulate force through increasing
      MLCP activity and that this effect is further potentiated through phosphorylation
      by cGMP in telokin-rich smooth tissues.

PMID- 16461921
TI  - Tensin3 is a novel thyroid-specific gene.
AB  - Thyroid-specific genes, such as thyroid peroxidase, thyroglobulin, Na+/I-
      symporter and thyroid-stimulating hormone receptor, play fundamental roles in
      thyroid function and relate to many pathological conditions. Using sequence
      specific-differential display, we detected three genes that showed higher
      expression levels in normal thyroid tissues than in thyroid tumor tissues. After
      subcloning and sequencing analysis, one of the genes was revealed to be tensin3.
      The expression level of tensin3 was examined with real-time quantitative PCR
      analysis. Its expression levels were more depressed in thyroid tumor tissues than
      in normal thyroid tissues. The decrease was even more evident in two anaplastic
      carcinomas. High and moderate levels of tensin3 mRNA expression were observed in
      the thyroid and placenta respectively. Tensin3 mRNA was expressed only in low
      levels in other tissues, such as the brain, heart, lung, liver, pancreas, kidney,
      skeletal muscle, white blood cells and prostate. These results show that tensin3
      is a novel thyroid-specific gene and further investigations may reveal its
      relation to thyroid function or thyroid disease.

PMID- 16461922
TI  - New insights into growth hormone action.
AB  - It has been 75 years since Evans and Long identified a somatic growth-promoting
      substance in pituitary extracts, yet it is only in the last 20 years that the
      molecular basis for this action has been established. Three key elements in this
      elucidation were the cloning of the GH receptor, the identification of Janus
      kinase (JAK) 2 as the receptor-associated tyrosine kinase, and the delineation of
      signal transduction and activators of transcription (STAT) 5a/b as the key
      transcription factor(s) activated by JAK2. The interaction between these three
      elements results in enhanced postnatal growth and is the subject of this review.
      We describe a new model for GH receptor activation based on subunit rotation
      within a constitutive dimer, together with the phenotype and hepatic transcript
      profile of mice with targeted knockins to the receptor cytoplasmic domain. These
      support a central role for STAT5a/b in postnatal growth.

PMID- 16461924
TI  - The co-existence of two growth hormone receptors in teleost fish and their
      differential signal transduction, tissue distribution and hormonal regulation of
      expression in seabream.
AB  - Two genomic contigs of putative growth hormone receptors (GHRs) were identified
      in fugu and zebrafish genomes by in silico analysis, suggesting the presence of
      two GHR subtypes in a single teleost species. We have tested this hypothesis by
      cloning the full-length cDNA sequence of a second GHR subtype from the black
      seabream in which the first GHR subtype had been previously reported by us. In
      addition, we had also cloned the sequences of both GHR subtypes from two other
      fish species, namely the Southern catfish and the Nile tilapia. Phylogenetic
      analysis of known GHR sequences from various vertebrates revealed that fish GHRs
      cluster into two distinct clades, viz. GHR1 and GHR2. One clade (GHR1),
      containing 6 to 7 extracellular cysteine residues, is structurally more akin to
      the non-teleost GHRs. The other clade (GHR2), containing only 4 to 5
      extracellular cysteine residues, is unique to teleosts and is structurally more
      divergent from the non-teleost GHRs. In addition, we had examined the biological
      activities of both GHR subtypes from seabream using a number of reporter
      transcription assays in cultured eukaryotic cells and demonstrated that both of
      them were able to activate the Spi 2.1 and beta-casein promoters upon receptor
      stimulation in a ligand specific manner. In contrast, only GHR1 but not GHR2 in
      seabream could trigger the c-fos promoter activity, indicating that the two GHR
      subtypes possess some differences in their signal transduction mechanisms. Also,
      the expression of GHR2 is significantly higher than GHR1 in many tissues of the
      seabream including the gonad, kidney, muscle, pituitary and spleen. In vivo
      hormone treatment data indicated that cortisol upregulated hepatic GHR1
      expression in seabream but not GHR2, whereas testosterone decreased hepatic GHR2
      expression but not GHR1. On the other hand, hepatic expression of both GHR1 and
      GHR2 in seabream was decreased by estradiol treatment.

PMID- 16461923
TI  - Mediation of the inhibitory effect of thyroid hormone on proliferation of
      hepatoma cells by transforming growth factor-beta.
AB  - Thyroid hormone (triiodothyronine, T3) regulates growth, development and
      differentiation. To examine the influence of T3 on hepatoma cell growth, thyroid
      receptor (TR)alpha1 or TRbeta1 over-expressing HepG2 cell lines were used. Growth
      of the HepG2-TR stable cell line was inhibited by over 50% following treatment
      with T3. However, transforming growth factor (TGF)-beta neutralizing antibody,
      but not the control antibody can reverse the cell growth inhibition effect of T3.
      Flow cytometric analysis indicated that the growth inhibition was apparent at the
      transition point between the G1 and S phases of the cell cycle. The expression of
      major cell cycle regulators was used to provide further evidence for the growth
      inhibition. Cyclin-dependent kinase 2 (cdk2) and cyclin E were down-regulated in
      HepG2-TR cells. Moreover, p21 protein or mRNA levels were up-regulated by around
      5-fold or 7.3-fold respectively following T3 treatment. Furthermore, phospho
      retinoblastoma (ppRb) protein was down-regulated by T3. The expression of TGF
      beta was studied to delineate the repression mechanism. TGF-beta was stimulated
      by T3 and its promoter activity was enhanced six- to eight-fold by T3.
      Furthermore, both T3 and TGF-beta repressed the expression of cdk2, cyclin E and
      ppRb. On the other hand, TGF-beta neutralizing but not control antibody blocked
      the repression of cdk2, cyclin E and ppRb by T3. These results demonstrated that
      T3 might play a key role in liver tumor cell proliferation.

PMID- 16461925
TI  - Role of MAP kinase phosphatases in GnRH-dependent activation of MAP kinases.
AB  - GnRH controls the synthesis and release of the pituitary gonadotropic hormones.
      MAP kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK)
      and c-Jun N-terminal kinase (JNK) pathways, are crucial for GnRH-induced gene
      activation. In the present study, we investigated the function of GnRH-induced
      MAPK phosphatases (MKPs) using an in vivo mouse model as well as the alphaT3-1
      cell line. Following GnRH agonist stimulation, in vivo gene profiling
      demonstrated that both MKP-1 and MKP-2 are induced with distinct temporal
      profiles, suggesting differential roles of these MKPs in the regulation of MAPK
      activation. Elevated activity of MKP-2 in alphaT3-1 cells, through either
      overexpression or activation of the endogenous MKP-2 gene, was correlated with
      inhibition of GnRH-induced activation of ERK and JNK, as well as the expression
      of ERK- and JNK-dependent proto-oncogenes. These data supported the conclusion
      that GnRH-induced MKPs likely serve as negative feedback regulators that modulate
      MAPK activity and function in the GnRH signaling pathway.

PMID- 16461926
TI  - Novel protein kinase C-epsilon inhibits human CYP11B2 gene expression through
      ERK1/2 signalling pathway and JunB.
AB  - We previously reported that H295R cells co-express three diacylglycerol (DAG)
      dependent protein kinase Cs (PKCs), namely conventional (c) PKCalpha and novel
      (n) PKCepsilon and PKCtheta. The aim of the present work was to evaluate the
      implication of DAG-dependent PKCs in the activation of p44/42 MAP kinase (MAPK)
      by angiotensin II (Ang II) and to define the role of this pathway towards CYP11B2
      regulation in H295R cells. The PKC inhibitor bisindolylmaleimide 1 (Bis)
      inhibited Ang II-induced p44/42 MAPK phosphorylation whereas the cPKC inhibitor
      Go6976 failed to do so, thus ruling out the participation of PKCalpha. Ang II
      activated nPKCepsilon and did not affect nPKCtheta, pinpointing PKCepsilon as the
      mediator of Ang II in p44/42 MAPK activation. Overexpression of wild-type ERK1
      and ERK2 significantly reduced basal as well as Ang II-stimulated human 
      2023CYP11B2-CAT activity; conversely, the two dominant negative mutants increased
      them. Overexpression of constitutively active (ca) PKCsuppressed Ang II-induced 
      2023CYP11B2-CAT activity. Infection of H295R cells with adenoviruses (Adv)
      expressing caPKCepsilon activated endogenous MEK1/2 and p44/42 MAPK. Adv
      caPKCepsilon inhibited Ang II-stimulated aldosterone synthase mRNA levels and
      this action was reversed by the MEK1 inhibitor, PD98059. Also, Ang II increased
      JunB protein levels and this effect was inhibited by PD98059 and Bis. Adv
      caPKCepsilon enhanced JunB protein levels and PD98059 attenuated the increase.
      JunB overexpression abolished the Ang II-induced promoter activity within -138 bp
      of the 5'-flanking region of CYP11B2. Collectively, these results demonstrate
      that PKCepsilon inhibits CYP11B2 transcription through the p44/42 MAPK pathway
      and JunB in H295R cells.

PMID- 16461927
TI  - Neurohypophysial dysmorphogenesis in mice lacking the homeobox gene Uncx4.1.
AB  - A number of transcription factors have been implicated in the development of the
      hypothalamo-neurohypophysial system (HNS). Null mutations for these factors
      caused severe defects in proliferation, migration and survival during early
      embryogenesis. While they have informed about early events of HNS developments no
      insights in mechanisms of late development and maturation of this major
      peptidergic system have been obtained as yet. In a screen for adult-expressed
      homeobox genes we identified Uncx4.1 as a gene expressed in adult and embryonic
      magnocellular neurons of the (HNS). Null mutation of Uncx4.1 left these neurons
      viable and able to express neuropeptides. However, the connectivity of
      magnocellular neurons with posterior pituitary elements was compromised. As a
      consequence neuronal fibres traversed to the adenohypophysis. The penetrance of
      this phenotype was about 50%. The data show a selective role of Uncx4.1 in
      controlling the development of connections of hypothalamic neurons to pituitary
      elements, allowing central neurons to reach the peripheral blood circulation and
      to deliver hormones for control of peripheral functions.

PMID- 16461928
TI  - Disruption of neuromedin B receptor gene results in dysregulation of the
      pituitary-thyroid axis.
AB  - The level of thyrotropin (TSH) secretion is determined by the balance of TSH
      releasing hormone (TRH) and thyroid hormones. However, neuromedin B (NB), a
      bombesin-like peptide, highly concentrated in the pituitary, has been postulated
      to be a tonic inhibitor of TSH secretion. We studied the pituitary-thyroid axis
      in adult male mice lacking NB receptor (NBR-KO) and their wild-type (WT)
      littermates. At basal state, NBR-KO mice presented serum TSH slightly higher than
      WT (18%, P< 0.05), normal intra-pituitary TSH content, and no significant changes
      in alpha and beta TSH mRNA levels. Serum thyroxine was normal but serum
      triiodothyronine (T3) was reduced by 24% (P< 0.01) in NBR-KO mice. Pituitaries of
      NBR-KO mice exhibited no alteration in prolactin mRNA expression but type I and
      II deiodinase mRNA levels were reduced by 53 and 42% respectively (P< 0.05),
      while TRH receptor mRNA levels were importantly increased (78%, P< 0.05). The TSH
      releasing effect of TRH was significantly higher in NBR-KO than in WT mice (7.1
      and 4.0-fold respectively), but, while WT mice presented a 27% increase in serum
      T3 (P< 0.05) after TRH, NBR-KO mice showed no change in serum T3 after TRH. NBR
      KO mice did not respond to exogenous NB, while WT showed a 30% reduction in serum
      TSH. No compensatory changes in mRNA expression of NB or other bombesin-related
      peptides and receptors (gastrin-releasing peptide (GRP), GRP-receptor and
      bombesin receptor subtype-3) were found in the pituitary of NBR-KO mice.
      Therefore, the data suggest that NB receptor pathways are importantly involved in
      thyrotroph gene regulation and function, leading to a state where TSH release is
      facilitated especially in response to TRH, but probably with a less-bioactive
      TSH. Therefore, the study highlights the important role of NB as a physiological
      regulator of pituitary-thyroid axis function and gene expression.

PMID- 16461929
TI  - The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene
      identified by DNA microarray analysis are directly regulated by estrogen
      receptor.
AB  - Recent studies have revealed that hundreds of genes in the uterus are activated
      by estrogen. Their expression profiles differ over time and doses and it is not
      clear whether all these genes are directly regulated by estrogen via the estrogen
      receptor. To select the genes that may be regulated by estrogen, we treated mice
      with several doses of estrogen and searched for those genes whose dose-response
      expression pattern mirrored the uterine growth pattern. Among those genes, we
      found that the dose-dependent expression of the adrenomedullin (ADM) gene
      correlated well with the uterotrophic effect of estrogen. ADM expression is
      induced early after estrogen administration and is restricted to the endometrial
      stroma. The spatiotemporal gene expression pattern of ADM was similar to that of
      receptor-modifying protein 3 (RAMP3). RAMP3 is known to modify calcitonin gene
      related receptor (CRLR) so that it can then serve as an ADM receptor. Chromatin
      immunoprecipitation assays indicated that the estrogen receptor binds directly to
      the ADM promoter region and RAMP3 intron after estrogen administration. It was
      also shown that neither the ADM nor RAMP3 gene could be activated in estrogen
      receptor-alpha-null mouse. Although uterine ADM expression has been reported to
      occur in the myometrium, our observations indicate that estrogen-induced ADM is
      also expressed in the uterine stroma and that such variable, spatiotemporally
      regulated ADM expression contributes to a wider range of biological effects than
      previously expected.

PMID- 16461930
TI  - Evidence that the mouse insulin receptor substrate-1 belongs to the gene family
      on which the promoter is activated by estrogen receptor alpha through its
      interaction with Sp1.
AB  - In the present study, the molecular mechanism underlying the up-regulatory effect
      of estradiol (E2) on mouse insulin receptor substrate-1 (IRS-1) promoter was
      investigated in CHO cells on which the same promoter had first been functionally
      characterized. The mouse IRS-1 promoter bears four consensus half Estrogen
      Responsive Elements (ERE) sequences and thirteen AP-1- and ten Sp1-binding
      elements. We performed molecular dissection of this promoter gene providing 3'
      different deleted constructs, containing the same AP-1 rich region with a
      progressively increased number of ERE half sites located downstream. None of
      these constructs was responsive to E2, while a downstream region (nt -1420 to 
      160) rich in GC elements was induced by E2. However, the latter region lost its
      intrinsic E2 responsiveness when the whole IRS-1 promoter was mutated for
      deletion in all four ERE half sites. Deletion analysis of the ERE half sites
      demonstrated that only ERE located at the position -1500 to -1495, close to the
      GC-rich region, was able to maintain the induced activatory effect of E2 on the
      IRS-1 gene. Electrophoretic mobility shift and chromatin immunoprecipitation
      assays identified the region containing the half ERE/Sp1 (nt -1500 to -1477) as
      the one conferring E2 responsiveness to the whole promoter. This effect occurs
      through the functional interaction between E2/ERalpha and Sp1.

PMID- 16461931
TI  - Spatio-temporal analysis of vascular endothelial growth factor expression and
      blood vessel remodelling in pig ovarian follicles during the periovulatory
      period.
AB  - Vascular endothelial growth factor (VEGF) expression pattern and blood vessel
      remodelling were evaluated during the transition from the preovulatory follicle
      to the corpus luteum (CL). To this end, prepubertal gilts were treated with
      equine chorionic gonadotrophin (eCG) to collect preovulatory follicles (60 h
      after eCG) and with human chorionic gonadotrophin (hCG) to obtain periovulatory
      follicles 18 h and 36 h later. The VEGF mRNA content was analysed by in situ
      hybridization, while protein localization in follicular fluid (FF) and in
      granulosa and theca compartments was evaluated by ELISA, immunohistochemistry or
      western blot. Blood vessel architecture and vascular area (VA) were investigated
      using immunohistochemistry for von Willenbrand Factor, a specific endothelial
      marker. Vascular remodelling was finally tested using Ki-67 immunocytochemistry
      as a proliferation marker, or alpha-smooth muscle actin (alpha-SMA) as a specific
      mural cell marker. eCG-treated follicles showed high VEGF levels and two
      concentric blood vessel networks composed of proliferating endothelial cells
      without any association with mural components. hCG injection inhibited VEGF
      synthesis in the granulosa compartment and, as a consequence, the protein fell
      within the FF. In parallel, endothelial cell proliferation stopped and the VA
      decreased. Close to ovulation, VEGF production restarted in both follicular
      compartments and VEGF mRNA content significantly increased in the theca layer.
      Changes in follicular VEGF secretion were observed; the protein disappeared from
      FF and was observed in the extracellular matrix. An active angiogenesis
      characterized the follicle; endothelial cell proliferation was associated with a
      recruitment of alpha-SMA-positive mural cells. The data presented in this work
      showed that, in the phases preceding ovulation, a complete vascular remodelling
      occurs, characterized by both an evident neovascularization and the appearance of
      blood vessels presenting smooth musculature which could be involved in CL
      formation after ovulation.

PMID- 16461932
TI  - Tetraspanin CD9 regulates invasion during mouse embryo implantation.
AB  - The expression of tetraspanin CD9 was found on blastocysts in mice and
      endometrium epithelial cells in human and bovine. However, it remains unknown how
      CD9 is involved in the precise dialogue between embryo and uterus during early
      pregnancy. This study was designed to investigate the functional roles of CD9 in
      the embryo implantation with monoclonal antibody against CD9 protein (anti-CD9
      mAb) and antisense oligonucleotide against CD9 gene (AS-CD9). Our results showed
      that intrauterine injection of anti-CD9 mAb on day 4 of pregnancy significantly
      increased the number of embryos implanted (7.24+/-0.39 versus 4.04+/-0.38). In
      vitro, anti-CD9 mAb or AS-CD9 significantly enhanced embryo-outgrowth ability on
      the monolayer of uterus epithelial cells in a dose-dependent manner. However, the
      attachment of blastocysts to epithelial cells was unaffected. Furthermore, we
      found that anti-CD9 mAb or AS-CD9 stimulated matrix metalloproteinase 2 (MMP-2)
      production of blastocysts on Fibronectin. LY294002, a specific inhibitor of
      phosphoinositide 3-kinase, was able to counteract the effect of anti-CD9 mAb and
      AS-CD9 on outgrowth ability and production of MMP-2. Our results indicated that
      CD9 played a role of inhibiting embryo implantation. CD9 was able to impair
      embryo invasion and the production of MMP-2 through the phosphoinositide 3-kinase
      signaling pathway.

PMID- 16461933
TI  - Central and/or peripheral immunoreactivity of orexin-A in pregnant rats and
      women.
AB  - Orexins (A and B) have been implicated in feeding behavior, energy balance and
      state of vigilance. During pregnancy, their involvement in feeding regulation and
      reproduction are poorly understood. In this study, we investigated orexin-A
      immunoreactivity in the hypothalamus and serum in pregnant rats and women by
      immunofluorescence staining, image analysis and radioimmunoassay, examined the
      correlation of serum orexin-A and leptin with gestational age in pregnant women
      by regression analysis, and explored the effect of leptin injected
      intracerebroventricularly (i.c.v.) on orexin-A immunoreactivity in the
      hypothalamus of normal rats by immunohistochemistry. The results showed that
      pregnant rats had significantly greater daily food intake on days 15 and 20 of
      pregnancy than virgin ones (+27.3%, P< 0.01 and +38.6%, P< 0.001 respectively),
      with significantly fewer number and lower mean staining intensity of orexin-A
      immunoreactive (ir) neurons on days 16 (both P< 0.05) and 21 (both P< 0.01) of
      pregnancy. Moreover, serum levels of orexin-A exhibited 2.0-fold and 2.2-fold
      increases (both P< 0.001) in rats on days 16 and 21 of pregnancy compared with
      those in virgin rats, and 1.9-fold and 2.0-fold increases (both P< 0.001) in mid
      (13-26 weeks) and late pregnant women (27-40 weeks) compared with those in non
      pregnant women. Simultaneously, serum levels of leptin showed a 2.3-fold and 2.2
      fold increase (both P< 0.001) in rats on days 16 and 21 of pregnancy, and a 3.3
      fold and 4.3-fold increase (both P< 0.001) in mid and late pregnant women. Serum
      levels of both orexin-A and leptin correlated positively with gestational age in
      pregnant women. Leptin injected i.c.v. significantly decreased the number (P<
      0.01) and mean staining intensity (P< 0.01) of orexin-A-ir neurons in the
      hypothalamus, food intake (P< 0.01) and body weight gain (P< 0.001) compared with
      vehicle injection in normal rats. These results suggested that central and serum
      orexin-A might be involved in the regulation of feeding and energy metabolism
      during pregnancy. The change in central orexin-A immunoreactivity might be
      related to the increased serum leptin concentrations.

PMID- 16461934
TI  - Temporal recruitment of CCAAT/enhancer-binding proteins to early and late
      adipogenic promoters in vivo.
AB  - The CCAAT/enhancer-binding protein (C/EBP) family of transcriptional regulators
      is critically important for the activation of adipogenic genes during
      differentiation. The C/EBPbeta and delta isoforms are rapidly induced upon
      adipocyte differentiation and are responsible for activating the adipogenic
      regulators C/EBPalpha and peroxisome proliferator activated receptor
      (PPAR)gamma2, which together activate the majority of genes expressed in
      differentiating adipocytes. However, mitosis is required following the induction
      of adipogenesis, and the activation of C/EBPalpha and PPARgamma2 gene expression
      is delayed until cell division is underway. Previous studies have used
      electromobility shift assays to suggest that this delay is due, at least in part,
      to a delay between the induction of C/EBPbeta protein levels and the acquisition
      of DNA binding capacity by C/EBPbeta. Here we used in vivo chromatin
      immunoprecipitation analysis of the C/EBPalpha, PPARgamma2, resistin,
      adiponectin, and leptin promoters to examine the kinetics of C/EBP protein
      binding to adipogenic genes in differentiating cells. In contrast to prior
      studies, we determined that C/EBPbeta and delta were bound to endogenous
      regulatory sequences controlling the expression of these genes within 1-4 h of
      adipogenic induction. These results indicated that C/EBPbeta and delta bind not
      only to genes that are induced early in the adipogenic process but also to genes
      that are induced much later during differentiation, without a delay between
      induction of C/EBP protein levels and DNA binding by these proteins. We also
      showed that each of the genes examined undergoes a transition in vivo from early
      occupancy by C/EBPbeta and delta to occupancy by C/EBPalpha at times that
      correlate with the induction of C/EBPalpha protein levels, demonstrating the
      generality of the transition during adipogenesis and indicating that the binding
      of specific C/EBP isoforms does not correlate with timing of expression from each
      gene. We have concluded that C/EBP family members bind to adipogenic genes in
      vivo in a manner that follows the induction of C/EBP protein synthesis.

PMID- 16461935
TI  - The appetite suppressant d-fenfluramine reduces water intake, but not food
      intake, in activity-based anorexia.
AB  - Biochemical, genetic and imaging studies support the involvement of the serotonin
      (5-HT) system in anorexia nervosa. Activity-based anorexia (ABA) is considered an
      animal model of anorexia nervosa, and combines scheduled feeding with voluntary
      running wheel activity (RWA). We investigated the effect of d-fenfluramine (d
      FEN) treatment on development and propagation of ABA. d-FEN is an appetite
      suppressant and acts on 5-HT(2C) receptors that are located on pro
      opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. Since
      stimulation activation of the melanocortin system stimulates ABA, we hypothesized
      that d-FEN treatment enhances the development and propagation of ABA. Rats were
      exposed to the ABA model and chronically infused with d-FEN. Unexpectedly, d-FEN
      treated ABA rats did not reduce food intake or increase wheel running as compared
      with vehicle-treated ABA rats. Furthermore d-FEN treatment did not affect body
      weight loss, hypothalamus-pituitary-adrenal axis activation, or starvation
      induced hypothermia in ABA rats. POMC mRNA levels in d-FEN-treated rats were not
      different from vehicle-treated rats after one week of exposure to the ABA
      paradigm. However, d-FEN-treated ABA rats showed hypodypsia and increased plasma
      osmolality and arginine-vasopressin expression levels in the hypothalamus. We
      conclude that d-FEN treatment does not enhance ABA under the experimental
      conditions of this study, but strongly reduces water intake in ABA rats.

PMID- 16461936
TI  - Leptin resistance following over-expression of protein tyrosine phosphatase 1B in
      liver.
AB  - Obesity is typically associated with resistance to leptin, yet the mechanism by
      which leptin signaling becomes impaired is poorly understood. Here we sought to
      determine if the development of obesity and leptin resistance correlates with
      increased expression of protein tyrosine phosphatase 1B (PTP1B) in peripheral
      tissues and whether over-expression of this phosphatase, specifically in liver,
      could alter the leptin-mediated effects on feeding and glucose metabolism.
      Obesity was induced in mice through a high-fat diet that resulted in
      hyperglycemia, hyperinsulinemia and hyperleptinemia. Resistance to leptin was
      confirmed as exogenous leptin administration reduced food intake in animals on
      low-fat, but not high-fat diets. Diet-induced resistance to leptin and insulin
      was associated with increased hepatic levels of PTP1B. Intriguingly, hepatic
      adenoviral over-expression of PTP1B in ob/ob mice attenuated the ability of
      exogenous leptin to reduce both plasma glucose levels and food intake. These
      findings suggest that leptin reduces both plasma glucose and food intake in part
      through actions on the liver, and hepatic leptin resistance resulting from over
      expression of PTP1B may contribute to the development of both diabetes and
      obesity.

PMID- 16461937
TI  - Female-enriched and thermosensitive expression of steroidogenic factor-1 during
      gonadal differentiation in Pleurodeles waltl.
AB  - In the urodele amphibian Pleurodeles waltl, sex differentiation is genetically
      controlled, that is, ZZ male vs ZW female, but may be influenced by temperature,
      which induces a female-to-male sex reversal. We investigated whether
      steroidogenic factor 1 (SF-1) could be involved in Pleurodeles sex
      differentiation or in temperature-dependent sex reversal by cloning a Pleurodeles
      SF-1 cDNA and examining its developmental expression. The 468-amino-acid deduced
      protein is highly conserved in comparison with other species. In ZZ and ZW
      control larvae, SF-1 mRNA is detected at the first stage of the thermosensitive
      period (TSP) in the gonad-mesonephros-interrenal complex (GMI). By the end of TSP
      at stage 55, SF-1 is expressed in the gonad (Gd) and in the mesonephros
      interrenal (MI) both in ZZ and ZW larvae. During this stage, a transient, ZW
      specific increase of SF-1 transcription occurs not only in Gd but also in MI,
      this increase starting earlier in Gd than in MI. Therefore, in P. waltl, an SF-1
      upregulation occurs after the onset of the ovarian-specific increase of aromatase
      mRNA expression. At the end of metamorphosis, the SF-1 transcription level in Gd
      and MI is nearly the same in both ZZ and ZW larvae. Besides, after long-term heat
      treatment leading to sex reversal, SF-1 mRNA upregulation is not observed in ZW
      larvae, in either Gd or MI. However, SF-1 expression is not decreased after a 48
      h heat shock applied at the end of the TSP, suggesting that temperature has no
      inhibitory effect by itself in long-term heat treatment. Estradiol benzoate
      treatments show that, at the end of the TSP, SF-1 gene transcription could be
      controlled by the estrogen level. This is in accordance with the female-enriched
      SF-1 expression and the decreased SF-1 expression following long-term, sex
      reversing heat treatment, which is known to decrease aromatase expression and
      activity. Thus, it is unlikely that SF-1 is directly involved in Pleurodeles
      temperature-dependent sex reversal.

PMID- 16461938
TI  - Identification and characterization of a novel isoform of the vesicular gamma
      aminobutyric acid transporter with glucose-regulated expression in rat islets.
AB  - Pancreatic islets are unique outside the nervous system in that they contain high
      levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA),
      synthesized by the enzyme glutamic acid decarboxylase (GAD). Since the role that
      GABA plays in the islet and the mechanisms whereby the two major GAD isoforms
      (GAD65 and GAD67) function as diabetes-associated autoantigens are unknown,
      continued characterization of the islet GAD-GABA system is important. We
      previously demonstrated that the GABA and glycine transporter vesicular
      inhibitory amino acid transporter (VIAAT also known as VGAT) is present in rat
      islets. Here we identify a novel 52 kDa variant of VIAAT in rat islets: VIAAT-52
      (V52). V52 is an amino-terminally truncated form of VIAAT (V57) that likely
      results from utilization of a downstream start site of translation. V57 and V52
      display different patterns of post-translational modification and cellular
      expression. Our results have indicated that islet content of V52, but not V57, is
      responsive to changes in glucose concentration and other extracellular
      conditions. VIAAT is expressed in the islet alpha cells, but there have been
      conflicting findings regarding the presence of VIAAT in the beta cells. Here we
      have also provided additional evidence for the presence of VIAAT in islet beta
      cells and show that the beta cell line INS-1 expresses V57. V52 may be better
      adapted than V57 to the unique rat alpha cell GAD-GABA system, which lacks GAD65
      and in which VIAAT traffics to secretory granules rather than just to synaptic
      microvesicles.

PMID- 16461939
TI  - Acute regulation of murine follicle-stimulating hormone beta subunit
      transcription by activin A.
AB  - In rodents, activins stimulate immediate-early increases in pituitary follicle
      stimulating hormone beta (Fshb) subunit transcription. Here, we investigated the
      underlying signaling mechanisms using the mouse gonadotrope cell line, LbetaT2.
      Activin A increased mouse Fshb-luciferase reporter activity within 4 h through a
      Smad-dependent signaling pathway. The ligand rapidly stimulated formation of
      SMAD2/3/4 complexes that could interact with a consensus palindromic Smad binding
      element (SBE) in the proximal Fshb promoter. SMAD over-expression potently
      stimulated transcription, with the combination of SMADs 2, 3 and 4 producing the
      greatest synergistic activation. A mutation in the SBE that abolished Smad
      binding greatly impaired the effects of acute (4 h) activin A treatment and SMAD
      over-expression on promoter activity, but did not abolish the effects of chronic
      (24 h) activin A exposure. Within activated SMAD complexes, SMADs 3 and 4
      appeared to bind the SBE simultaneously and the binding of both was required for
      maximal transcriptional activation. Interestingly, the human FSHB promoter, which
      lacks the consensus SBE, was neither rapidly stimulated by activin A nor by over
      expressed SMADs, but was activated by 24 h activin A. Addition of the SBE to the
      human promoter increased both SMAD2/3/4-sensitivity and acute regulation by
      activin A, though not to levels observed in mouse. We postulate that short
      reproductive cycles in female rodents, particularly the brief interval between
      the primary and secondary FSH surges of the estrous cycle, require the Fshb
      promoter in these animals to be particularly sensitive to the rapid, Smad
      dependent actions of activins on transcription. The human FSHB promoter, in
      contrast, is chronically regulated by activins seemingly through a SMAD
      independent pathway.

PMID- 16461940
TI  - Transcriptional regulation of the rat apelin receptor gene: promoter cloning and
      identification of an Sp1 site necessary for promoter activity.
AB  - The genomic structure and transcriptional regulation of the rat apelin receptor
      (APJR) were analysed by rapid amplification of 5' cDNA ends (5'-RACE), transient
      expression assays and DNA-protein interaction. Analysis of the 5'-flanking region
      of a rat genomic clone shows no TATA box, but a putative CAAT box and several
      putative binding sites for transcription factors are present. Two transcriptional
      start sites were identified by 5'-RACE, RNase protection and primer extension
      analyses. Promoter activity was exhibited in the APJR- expressing SH-SY5Y cell
      line as well as in COS-7 and Chinese hamster ovary (CHO-K1) cells. Consecutive 5'
      deletion analysis revealed the highest promoter activity in a region between bp 
      966 and -165. DNaseI footprint analysis revealed seven protected regions and
      electrophoretic mobility shift, super-shift and competition assays identified
      individual DNA-protein complexes capable of binding Sp1, estrogen receptor
      (ER)alpha, glucocorticoid receptor and CCAAT enhancer binding protein
      (C/EBP)gamma transcription factors. Site-directed mutagenesis identified an
      individual Sp1 motif that plays a major role in activation of the APJR promoter
      and also demonstrated constitutive transcriptional regulation of the promoter by
      estrogen and glucocorticoid receptors. Promoter regulation by the cAMP-dependent
      signal cascade was also shown.

PMID- 16461941
TI  - Immobilized pH gradient isoelectric focusing as a first-dimension separation in
      shotgun proteomics.
AB  - Shotgun proteomics, where a tryptic digest of a complex proteome sample is
      directly analyzed by either single dimensional or multidimensional liquid
      chromatography tandem mass spectrometry, has gained acceptance in the proteomics
      community at large and is widely used in core facilities. Here we review the
      development in our laboratory of an alternative first-dimension separation
      technique for shotgun proteomics, immobilized pH gradient isoelectric focusing
      (IPG-IEF). The key advantages of the technology over other multidimensional
      separation formats (simplicity, high resolution, and high sensitivity) are
      discussed. The concept of using peptide pI to filter large shotgun proteomics
      datasets generated by the IPG-IEF technique to minimize false positives and
      negatives is also introduced. Finally, an account of the comparison of the
      technique with the established gold standard for multidimensional separation of
      peptides, strong cation exchange chromatography, is presented, along with the
      prospects for the use of peptide pI along with accurate mass measurement for the
      identification of peptides.

PMID- 16461942
TI  - Multistep mass tagging coupled with 2D LC-MS--an approach to increasing the
      number of identified proteins.
AB  - Identification of large numbers of proteins from complex biological samples is a
      continuing challenge in the area of quantitative proteomics. We introduce here a
      simple and reliable multistep mass tagging technique using our recently developed
      solid phase mass tagging reagents. When coupled with two-dimensional liquid
      chromatography/nano-electrospray ionization ion trap mass spectrometry (2D
      LC/nano-ESI-MS), this method allows enhanced protein identification when tested
      on samples from prokaryotic and eukaryotic sources. The proteome of Escherichia
      coli D21 grown to either mid-exponential or stationary phase, and the membrane
      proteome from established breast cancer cell lines BT474 and MCF7 were used as
      model systems in these experiments. In both experiments, the numbers of total
      identified proteins are at least twice the numbers identified from a single
      tagging cycle. The sample complexity can be effectively reduced with
      corresponding increases in protein identification using the multistep method. The
      strategy described here represents a potentially powerful technique for large
      scale qualitative and quantitative proteome research.

PMID- 16461943
TI  - Screening for transglutaminase-catalyzed modifications by peptide mass finger
      printing using multipoint recalibration on recognized peaks for high mass
      accuracy.
AB  - Detection of posttranslational modifications is expected to be one of the major
      future experimental challenges for proteomics. We describe herein a mass
      spectrometric procedure to screen for protein modifications by peptide mass
      fingerprinting that is based on post-data acquisition improvement of the mass
      accuracy by exporting the peptide mass values into analytical software for
      multipoint recalibration on recognized peaks. Subsequently, the calibrated peak
      mass data set is used in searching for modified peptides, i.e., peptides
      possessing specific mass deviations. In order to identify the location of Lys-
      and Gln-residues available for transglutaminase-catalyzed isopeptide bond
      formation, mammalian small heat shock proteins (sHsps) were screened for labeling
      with the two hexapeptide probes GQDPVR and GNDPVK in presence of
      transglutaminase. Peptide modification due to cross-linking of the GQDPVR hexa
      peptide probe was detected for C-terminal Lys residues. Novel transglutaminase
      susceptible Gln sites were identified in two sHsps (Q31/Q27 in Hsp20 and HspB2,
      respectively), by cross-linking of the GNDPVK hexapeptide probe. Deamidation of
      specific Gln residues was also detected, as well an isopeptide derived from
      intramolecular Gln-Lys isopeptide bond formation. We conclude that peptide mass
      fingerprinting can be an efficient way of screening for various posttranslational
      modifications. Basically any instrumentation for MALDI mass spectrometry can be
      used, provided that post-data acquisition recalibration is applied.

PMID- 16461944
TI  - Characterization of protein glycosylation using chip-based nanoelectrospray with
      precursor ion scanning quadrupole linear ion trap mass spectrometry.
AB  - Glycosylation is one of the most important posttranslational modifications
      affecting the functions of proteins and cell activities. Mass spectrometry (MS)
      has proven to be an effective tool for structural glycobiology and has helped
      gain an understanding of glycoprotein-mediated diseases. Although electro-spray
      ionization-tandem MS remains widely recognized as an effective means for
      oligosaccharide characterization, the hydrophilic nature of glycans has often
      caused the poor ionization efficiency requiring either derivatization or
      nanoelectrospray to improve detection sensitivity. In this report we describe the
      use of a chip-based infusion nanoelectrospray platform coupled with the hybrid
      triple quadrupole/linear ion trap for identification and characterization of
      glycosylation in complex mixtures. The high-mannose-type N-glycosylation in
      ribonuclease B was used to map the glycosylation site and obtain glycan
      structures. Using the chip-based nanoelectro-spray with precursor ion scanning
      linear ion trap MS, we were able to map the glycosylation site and obtain the
      glycan structures in ribonuclease B at 100 fmol/microL in a single analysis. In
      addition, a new, low-abundant glycoform with an additional hexose (Hex10GlcNAc2)
      attached to ribonuclease B was discovered. The results reported here demonstrate
      that the chip-based infusion nanoelectrospray ionization coupled to a
      quadrupole/linear ion trap platform is a valuable system, as it provides high
      sensitivity and stability for nanoelectrospray analysis, and allows extended
      acquisition time for completing precursor ion scanning and subsequent MS2 and MS3
      information in a single analysis.

PMID- 16461945
TI  - Simple modifications of the standard DNA sequencing protocol allow for sequencing
      through siRNA hairpins and other repeats.
AB  - RNAi is a relatively new but powerful technology used for monitoring gene
      silencing in many species. The RNA corresponding to the gene of interest can be
      delivered into cells using various protocols, but the approach where both sense
      and antisense strands are located in the same transcript seems to be the most
      promising. However, the DNA sequencing step is a challenge due to the formation
      of a strong hairpin structure. In this work we present a very simple modification
      to the standard DNA sequencing protocol that allows sequencing through such
      difficult regions. The modification does not require any additional enzymatic or
      chemical manipulations. It simply adds a 5-min heat-denaturation step at 98
      degrees C, prior to addition of a Taq mix. The inclusion of this step is very
      effective in sequencing through many different categories of difficult templates.
      Other examples of the implementation of this step have been described previously
      and more detailed information on heat-denaturation of plasmid DNAs has been
      presented.

PMID- 16461947
TI  - Monitoring the disruption of nuclear envelopes in interphase cells with GFP-beta
      galactosidase.
AB  - The nuclear envelope of eukaryotic cells provides a barrier separating nucleus
      from cytoplasm, thereby regulating the exchange of macromolecules between both
      compartments. However, in cells exposed to severe forms of stress this barrier
      may break down, resulting in the mixing of nuclear and cytoplasmic contents. We
      show here that the fusion protein GFP-beta-galactosidase can be used to evaluate
      the intactness of nuclear envelopes in HeLa cells that have been exposed to heat
      and oxidative stress. GFP-beta-galactosidase is restricted to the cytoplasm of
      interphase cells, but enters the nucleus when nuclear membranes are disrupted.
      For comparison, we have analyzed the barrier function of nuclear membranes with
      antibodies against lamin B. Treatment of fixed cells with digitonin permeabilizes
      the plasma membrane, but leaves nuclear envelopes intact. Consequently, after
      digitonin incubation antibodies to lamin B can bind their antigen only if nuclear
      membranes are damaged. For various heat and oxidative stress conditions, we have
      compared the distribution of GFP-beta-galactosidase with the accessibility of
      lamin B to antibodies. Our results demonstrate that nuclear envelopes are
      permeable to antibodies whenever GFP-beta-galactosidase enters the nucleus. GFP
      beta-galactosidase is therefore a useful tool for evaluating the disintegration
      of the nuclear envelope and identifying cells in which a mixing of nuclear and
      cytoplasmic material takes place.

PMID- 16461946
TI  - Nucleic acid aptamers for target validation and therapeutic applications.
AB  - In the simplest view, aptamers can be thought of as nucleic acid analogs to
      antibodies. They are able to bind specifically to proteins, and, in many cases,
      that binding leads to a modulation of protein activity. New aptamers are rapidly
      generated through the SELEX (Systematic Evolution of Ligands by Exponential
      enrichment) process and have a very high target affinity and specificity
      (picomoles to nanomoles). Furthermore, aptamers composed of modified nucleotides
      have a long in vivo half-life (hours to days), are nontoxic and nonimmunogenic,
      and are easily produced using standard nucleic acid synthesis methods. These
      properties make aptamers ideal for target validation and as a new class of
      therapeutics. As a target validation tool, aptamers provide important information
      that complements that provided by other methods. For example, siRNA is widely
      used to demonstrate that protein knock-out in a cellular assay can lead to a
      biological effect. Aptamers extend that information by showing that the dose
      dependent modulation of protein activity can be used to derive a therapeutic
      benefit. That is, aptamers can be used to demonstrate that the protein is a good
      target for drug development. As a new class of therapeutics, aptamers bridge the
      gap between small molecules and biologics. Like biologics, biologically active
      aptamers are rapidly discovered, have no class-specific toxicity, and are adept
      at disrupting protein-protein interaction. Like small molecules, aptamers can be
      rationally engineered and optimized, are nonimmunogenic, and are produced by
      scalable chemical procedures at moderate cost. As such, aptamers are emerging as
      an important source of new therapeutic molecules.

PMID- 16461948
TI  - Optimization of in vitro transcription and full-length cDNA synthesis using the
      T4 bacteriophage gene 32 protein.
AB  - We evaluated the effect of the T4 bacteriophage gene 32 protein (T4gp32) on in
      vitro transcription and reverse transcription. T4gp32 doubled the yield of in
      vitro transcripts obtained with T7 RNA polymerase and increased the yield of cDNA
      synthesis when used in combination with an RNaseH-deficient Moloney murine
      leukemia virus [Au: ok] reverse transcriptase. The positive effect could be
      correlated with the RNA chaperone activity of T4gp32. T4gp32 stimulated the
      synthesis of long cDNAs, particularly species longer than 7 kb. By comparison,
      thermal activation of reverse transcriptase with trehalose only boosted the
      production of shorter cDNAs. For the construction of an Arabidopsis thaliana cDNA
      library, where the average cDNA size is 1.2 kbp, both the presence of T4gp32
      under standard reaction conditions as well as thermal activation resulted in
      similarly high percentages of full-length cDNA. However, the inclusion of T4gp32
      in a standard reverse transcription reaction resulted in the highest cDNA yield.
      We conclude that the addition of T4gp32 in standard reverse transcription
      reactions can increase the quality and yield of full-length cDNA libraries.

PMID- 16461949
TI  - Automated template quantification for DNA sequencing facilities.
AB  - The quantification of plasmid DNA by the PicoGreen dye binding assay has been
      automated, and the effect of quantification of user-submitted templates on DNA
      sequence quality in a core laboratory has been assessed. The protocol pipets,
      mixes and reads standards, blanks and up to 88 unknowns, generates a standard
      curve, and calculates template concentrations. For pUC19 replicates at five
      concentrations, coefficients of variance were 0.1, and percent errors were from
      1% to 7% (n=198). Standard curves with pUC19 DNA were nonlinear over the 1 to
      1733 ng/microL concentration range required to assay the majority (98.7%) of user
      submitted templates. Over 35,000 templates have been quantified using the
      protocol. For 1350 user-submitted plasmids, 87% deviated by >or=20% from the
      requested concentration (500 ng/microL). Based on data from 418 sequencing
      reactions, quantification of user-submitted templates was shown to significantly
      improve DNA sequence quality. The protocol is applicable to all types of double
      stranded DNA, is unaffected by primer (1 pmol/microL), and is user modifiable.
      The protocol takes 30 min, saves 1 h of technical time, and costs approximately
      $0.20 per unknown.

PMID- 16461950
TI  - Assessment of some tools for the characterization of the human osteoarthritic
      cartilage proteome.
AB  - Since the proteome of osteoarthritic articular cartilage has been poorly
      investigated as yet, we adapted proteomic technologies to the study of the
      proteins secreted or released by fresh human osteoarthritic cartilage in culture.
      Fresh cartilage explants were obtained from three donors undergoing surgery for
      knee joint replacement. The explants were dissected out, minced, and incubated in
      serum-free culture medium. After 48 h, proteins in the medium were identified by
      two-dimensional or off-gel electrophoresis coupled to tandem mass spectrometry,
      or by using an antibody-based protein microarray designed to detect angiogenic
      factors, growth factors, chemokines, and cytokines. We identified a series of 43
      proteins. Some of these proteins were already described as secretion products of
      chondrocytes, such as YKL-39 or osteoprotegerin, while several other were known
      proteins but have never been reported previously in cartilage, such as the serum
      amyloid P-component, the vitamin D binding protein, the pigment epithelium
      derived factor, the pulmonary and activation-regulated chemokine, lyl-1,
      thrombopoietin, fibrinogen, angiogenin, gelsolin, and osteoglycin/mimecan. While
      this study enabled the identification of novel proteins secreted or released by
      human osteoarthritic cartilage, the goal of the present work was essentially to
      describe the technical approach necessary for a systematic study of
      osteoarthritic cartilages from a large population of donors, in order to be able
      to select the good markers and/or targets for this poorly explored disease.

PMID- 16461951
TI  - Analysis of one-step and two-step real-time RT-PCR using SuperScript III.
AB  - Real-time reverse transcription polymerase chain reaction (RT-PCR) is a commonly
      used technique to analyze gene expression. There has been little research
      conducted to test if SuperScript III quantitative one-step (reverse transcription
      carried out in the same tube as PCR) and two-step (reverse transcription carried
      out in a separate reaction) RT-PCR systems provide similar real-time results. In
      this study, real-time reactions were set up using the housekeeping genes
      glyceraldehyde phosphate dehydrogenase (GAPDH), beta2-microglobulin (B2M), and
      RNA polymerase 2 subunit A (PolR2A). Reaction efficiencies were determined by
      generating standard curves using total RNA isolated from human skeletal muscle
      and brain. Reaction efficiencies ranged from 97.7+/-0.9% to 99.4+/-1.8% for one
      step and 98.0+/-0.2% to 102.6+/-1.3% for two-step RT-PCR (R2 values for all
      reactions>or=0.995). The sensitivities of one-step and two-step methods, as
      measured by cycle threshold values, were similar for GAPDH and B2M. However, for
      the lesser expressed PolR2A mRNA there was a 5 cycle lower threshold for one
      step. In summary, both SuperScript III one-step and two-step methods yield
      reaction efficiencies close to 100% and produce similar, accurate, linear
      standard curves. However, using the one-step method with gene-specific priming
      may be more sensitive for quantification of certain genes such as PolR2A.

PMID- 16461952
TI  - Obesity in adolescent girls: is excess androgen the real bad actor?

PMID- 16461953
TI  - PTH expression, not always where you think ...

PMID- 16461954
TI  - Polyunsaturated fatty acids, inflammation, and cardiovascular disease: time to
      widen our view of the mechanisms.

PMID- 16461955
TI  - Saposin B binds and transfers phospholipids.
AB  - Saposin B (Sap B) is a member of a family of four small glycoproteins, Sap A, B,
      C, and D. Like the other three saposins, Sap B plays a physiological role in the
      lysosomal degradation of sphingolipids (SLs). Although the interaction of Sap B
      with SLs has been investigated extensively, that with the main membrane lipid
      components, namely phospholipids and cholesterol (Chol), is scarcely known. Using
      large unilamellar vesicles (LUVs) as membrane models, we have now found that Sap
      B simultaneously extracts from the lipid surface neutral [phosphatidylcholine
      (PC)] and anionic [phosphatidylinositol (PI)] phospholipids, fewer SLs
      [ganglioside GM1 (GM1) or cerebroside sulfate (CS)], and no Chol. More PI than SL
      (GM1 or CS) was solubilized from LUVs containing equal amounts of PI and SLs. An
      increase in PI level had a poor effect on the Sap B-induced solubilization of GM1
      or CS but strongly inhibited that of PC. Sap B was able not only to bind, but
      also to transfer phospholipids between lipid surfaces. Both the phospholipid
      binding and transfer activities were optimal at low pH values. These results
      represent the first biochemical analysis of the Sap B interaction with
      phospholipids. The capacity of Sap B to bind and transfer phospholipids occurs
      under conditions mimicking the interior of the late endosomal/lysosomal
      compartment and thus might have physiological relevance.

PMID- 16461957
TI  - Summaries for patients. Emergency room management of patients with suspected
      pulmonary embolism.

PMID- 16461956
TI  - Accurate energies of hydrogen bonded nucleic acid base pairs and triplets in tRNA
      tertiary interactions.
AB  - Tertiary interactions are crucial in maintaining the tRNA structure and
      functionality. We used a combined sequence analysis and quantum mechanics
      approach to calculate accurate energies of the most frequent tRNA tertiary base
      pairing interactions. Our analysis indicates that six out of the nine classical
      tertiary interactions are held in place mainly by H-bonds between the bases. In
      the remaining three cases other effects have to be considered. Tertiary base
      pairing interaction energies range from -8 to -38 kcal/mol in yeast tRNA(Phe) and
      are estimated to contribute roughly 25% of the overall tRNA base pairing
      interaction energy. Six analyzed posttranslational chemical modifications were
      shown to have minor effect on the geometry of the tertiary interactions.
      Modifications that introduce a positive charge strongly stabilize the
      corresponding tertiary interactions. Non-additive effects contribute to the
      stability of base triplets.

PMID- 16461958
TI  - Summaries for patients. Do the effects of blood pressure drugs differ by kidney
      function?

PMID- 16461959
TI  - Appropriateness of diagnostic management and outcomes of suspected pulmonary
      embolism.
AB  - BACKGROUND: International guidelines include several strategies for diagnosing
      pulmonary embolism with confidence, but little is known about how these
      guidelines are implemented in routine practice. OBJECTIVE: To evaluate the
      appropriateness of diagnostic management of suspected pulmonary embolism and the
      relationship between diagnostic criteria and outcome. DESIGN: Prospective cohort
      study with a 3-month follow-up. SETTING: 116 emergency departments in France and
      1 in Belgium. PATIENTS: 1529 consecutive outpatients with suspected pulmonary
      embolism. MEASUREMENTS: Appropriateness of diagnostic criteria according to
      international guidelines; incidence of thromboembolic events during follow-up.
      RESULTS: Diagnostic management was inappropriate in 662 (43%) patients: 36 of 429
      (8%) patients with confirmed pulmonary embolism and 626 of 1100 (57%) patients in
      whom pulmonary embolism was ruled out. Independent risk factors for inappropriate
      management were age older than 75 years (adjusted odds ratio, 2.27 [95% CI, 1.48
      to 3.47]), known heart failure (odds ratio, 1.53 [CI, 1.11 to 2.12]), chronic
      lung disease (odds ratio, 1.39 [CI, 1.00 to 1.94]), current or recent pregnancy
      (odds ratio, 5.92 [CI, 1.81 to 19.30]), currently receiving anticoagulant
      treatment (odds ratio, 4.57 [CI, 2.51 to 8.31]), and the lack of a written
      diagnostic algorithm and clinical probability scoring in the emergency department
      (odds ratio, 2.54 [CI, 1.51 to 4.28]). Among patients who did not receive
      anticoagulant treatment, 44 had a thromboembolic event during follow-up: 5 of 418
      (1.2%) patients who received appropriate management and 39 of 506 (7.7%) patients
      who received inappropriate management (absolute risk difference, 6.5 percentage
      points [CI, 4.0 to 9.1 percentage points]; P < 0.001). Inappropriateness was
      independently associated with thromboembolism occurrence (adjusted odds ratio,
      4.29 [CI, 1.45 to 12.70]). LIMITATIONS: This was an observational study without
      evaluation of the risk for overdiagnosis. CONCLUSIONS: Diagnostic management that
      does not adhere to guidelines is frequent and harmful in patients with suspected
      pulmonary embolism. Several risk factors for inappropriateness constitute useful
      findings for subsequent interventions.

PMID- 16461960
TI  - Prediction of pulmonary embolism in the emergency department: the revised Geneva
      score.
AB  - BACKGROUND: Diagnosis of pulmonary embolism requires clinical probability
      assessment. Implicit assessment is accurate but is not standardized, and current
      prediction rules have shortcomings. OBJECTIVE: To construct a simple score based
      entirely on clinical variables and independent from physicians' implicit
      judgment. DESIGN: Derivation and external validation of the score in 2
      independent management studies on pulmonary embolism diagnosis. SETTING:
      Emergency departments of 3 university hospitals in Europe. PATIENTS: Consecutive
      patients admitted for clinically suspected pulmonary embolism. MEASUREMENTS:
      Collected data included demographic characteristics, risk factors, and clinical
      signs and symptoms suggestive of venous thromboembolism. The variables
      statistically significantly associated with pulmonary embolism in univariate
      analysis were included in a multivariate logistic regression model. Points were
      assigned according to the regression coefficients. The score was then externally
      validated in an independent cohort. RESULTS: The score comprised 8 variables
      (points): age older than 65 years (1 point), previous deep venous thrombosis or
      pulmonary embolism (3 points), surgery or fracture within 1 month (2 points),
      active malignant condition (2 points), unilateral lower limb pain (3 points),
      hemoptysis (2 points), heart rate of 75 to 94 beats/min (3 points) or 95
      beats/min or more (5 points), and pain on lower-limb deep venous palpation and
      unilateral edema (4 points). In the validation set, the prevalence of pulmonary
      embolism was 8% in the low-probability category (0 to 3 points), 28% in the
      intermediate-probability category (4 to 10 points), and 74% in the high
      probability category (> or =11 points). LIMITATIONS: Interobserver agreement for
      the score items was not studied. CONCLUSIONS: The proposed score is entirely
      standardized and is based on clinical variables. It has sustained internal and
      external validation and should now be tested for clinical usefulness in an
      outcome study.

PMID- 16461961
TI  - Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline
      glomerular filtration rate.
AB  - BACKGROUND: Chronic kidney disease is common in older patients with hypertension.
      OBJECTIVE: To compare rates of coronary heart disease (CHD) and end-stage renal
      disease (ESRD) events; to determine whether glomerular filtration rate (GFR)
      independently predicts risk for CHD; and to report the efficacy of first-step
      treatment with a calcium-channel blocker (amlodipine) or an angiotensin
      converting enzyme inhibitor (lisinopril), each compared with a diuretic
      (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk
      patients with hypertension stratified by GFR. DESIGN: Post hoc subgroup analysis.
      SETTING: Multicenter randomized, double-blind, controlled trial. PARTICIPANTS:
      Persons with hypertension who were 55 years of age or older with 1 or more risk
      factors for CHD and who were stratified into 3 baseline GFR groups: normal or
      increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60
      to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction
      (< 60 mL/min per 1.73 m2; n = 5662 patients). INTERVENTIONS: Random assignment to
      chlorthalidone, amlodipine, or lisinopril. MEASUREMENTS: Rates of ESRD, CHD,
      stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart
      failure, and peripheral arterial disease). RESULTS: In participants with a
      moderate to severe reduction in GFR, 6-year rates were higher for CHD than for
      ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per
      1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with
      a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing
      CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]),
      stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart
      failure, and peripheral arterial disease), but less effective in preventing heart
      failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs.
      15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less
      effective in reducing stroke, combined CVD events, and heart failure.
      LIMITATIONS: Proteinuria data were not available, and combination therapies were
      not tested. CONCLUSIONS: Older high-risk patients with hypertension and reduced
      GFR are more likely to develop CHD than to develop ESRD. A low GFR independently
      predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to
      chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is
      superior to both for preventing heart failure, independent of level of renal
      function.

PMID- 16461962
TI  - Brief communication: Successful treatment of pure red-cell aplasia with an anti
      interleukin-2 receptor antibody (daclizumab).
AB  - BACKGROUND: Pure red-cell aplasia (PRCA) is a rare hematologic disease
      characterized by anemia, reticulocytopenia, and absence of bone marrow erythroid
      precursors. Most patients respond to some form of immunosuppressive treatment,
      but few prospective clinical trials have been performed. OBJECTIVE: To examine
      the efficacy of a humanized monoclonal antibody to the interleukin-2 receptor
      (daclizumab) for treating PRCA. DESIGN: Pilot study. SETTING: Federal government
      research hospital. PATIENTS: 15 patients with idiopathic PRCA. INTERVENTION:
      Daclizumab, 1 mg/kg of body weight, every 2 weeks for a total of 5 infusions.
      Pure red-cell aplasia was defined as transfusion-dependent anemia with a
      reticulocyte count of 60 x 10(9) cells/L or less and bone marrow showing absent
      or diminished erythroid precursors. MEASUREMENTS: Response to therapy was
      assessed by transfusion independence, increments in reticulocyte count, and
      nontransfused hemoglobin. RESULTS: Daclizumab had little toxicity. Of the 15
      patients, 6 patients (40%) responded to treatment. All responders became
      transfusion-independent and achieved normal or near-normal hemoglobin values and
      normal reticulocyte counts. LIMITATIONS: The study was unblinded, and the number
      of patients was too small to assess drug safety reliably. CONCLUSIONS: Daclizumab
      seems safe. Its efficacy in this pilot protocol suggests that expanded study in
      PRCA and other bone marrow failure syndromes is warranted.

PMID- 16461963
TI  - Nephrogenic diabetes insipidus.

PMID- 16461964
TI  - Update in hospital medicine.

PMID- 16461965
TI  - Translating clinical research into clinical practice: impact of using prediction
      rules to make decisions.
AB  - Clinical prediction rules, sometimes called clinical decision rules, have
      proliferated in recent years. However, very few have undergone formal impact
      analysis, the standard of evidence to assess their impact on patient care.
      Without impact analysis, clinicians cannot know whether using a prediction rule
      will be beneficial or harmful. This paper reviews standards of evidence for
      developing and evaluating prediction rules; important differences between
      prediction rules and decision rules; how to assess the potential clinical impact
      of a prediction rule before translating it into a decision rule; methodologic
      issues critical to successful impact analysis, including defining outcome
      measures and estimating sample size; the importance of close collaboration
      between clinical investigators and practicing clinicians before, during, and
      after impact analysis; and the need to measure both efficacy and effectiveness
      when analyzing a decision rule's clinical impact. These considerations should
      inform future development, evaluation, and use of all clinical prediction or
      decision rules.

PMID- 16461966
TI  - Better care for patients with suspected pulmonary embolism.

PMID- 16461967
TI  - Which antihypertensive agents in chronic kidney disease?

PMID- 16461968
TI  - Transport.

PMID- 16461969
TI  - The middle time.

PMID- 16461970
TI  - Acute exacerbations in idiopathic pulmonary fibrosis.

PMID- 16461971
TI  - Quality of care for vulnerable older patients.

PMID- 16461972
TI  - Presentation of diagnostic test accuracy.

PMID- 16461973
TI  - The pitfalls of introducing electronic medical records.

PMID- 16461974
TI  - Presentation of diagnostic test accuracy.

PMID- 16461975
TI  - Thyrotoxicosis as a risk factor for pulmonary arterial hypertension.

PMID- 16461976
TI  - Liver transplantation in HIV-seropositive individuals.

PMID- 16461977
TI  - Savings from Canadian Internet pharmacies are limited.

PMID- 16461978
TI  - Undisclosed conflicts of interest.

PMID- 16461979
TI  - Regression of cutaneous and gastrointestinal telangiectasia with sirolimus and
      aspirin in a patient with hereditary hemorrhagic telangiectasia.

PMID- 16461980
TI  - Independence of genetic geographical variation between photoperiodic diapause,
      circadian eclosion rhythm, and Thr-Gly repeat region of the period gene in
      Drosophila littoralis.
AB  - Drosophila littoralis is a latitudinally widespread European species of the
      Drosophila virilis group. The species has ample genetic variation in
      photoperiodism (adult diapause) and circadian rhythmicity (pupal eclosion
      rhythm), with adaptive latitudinal clines in both of them. The possible common
      genetic basis between the variability of photoperiodism and circadian rhythms was
      studied by a long-term crossing experiment. A northern strain (65 degrees N)
      having long critical day length (CDL = 19.9 h) for diapause, early phase of the
      entrained rhythm in LD 3:21 (psi(LD3:21) = 12.3 h), and short period (tau= 18.8
      h) of the free-running rhythm for the eclosion rhythm was crossed with a southern
      strain (42 degrees N) having short CDL (12.4 h), late eclosion phase (psi(LD3:21)
      = 20.2 h), and long period (tau= 22.8 h). After 54 generations, including free
      recombination, artificial selection, and genetic drift, a novel strain resulted,
      having even more "southern" diapause and more "northern" eclosion rhythm
      characteristics than found in any of the geographical strains. The observed
      complete separation of eclosion rhythm characteristics from photoperiodism is a
      new finding in D. littoralis; in earlier studies followed for 16 generations, the
      changes had been mostly parallel. Evidently, the genes controlling the
      variability of the eclosion rhythm and photoperiodism in D. littoralis are
      different but closely linked. To test for the possible gene loci underlying the
      observed geographical variability, the period gene was studied in 10 strains
      covering all the known clock variability in D. littoralis. The authors sequenced
      the most suspected Thr-Gly region, which is known to take part in the adaptive
      clock variability in Drosophila melanogaster. No coding differences were found in
      the strains, showing that this region is not included in the adaptive clock
      variability in D. littoralis.

PMID- 16461981
TI  - Non-ventral lateral neuron-based, non-PDF-mediated clocks control circadian egg
      laying rhythm in Drosophila melanogaster.
AB  - The authors report the results of their study aimed at investigating the
      consequence of targeted ablation of ventral lateral neurons (LN(v)s--neurons
      regulating eclosion and locomotor activity rhythms) and genetic disruption of
      pigment-dispersing factor (PDF--an important output of circadian clocks) on the
      egg-laying rhythm of Drosophila melanogaster. The results clearly suggest that
      genetic ablation of LN(v)s and loss of function mutation of PDF abolish eclosion
      and locomotor activity rhythms, whereas the egg-laying rhythm continues unabated.
      Furthermore, the results also demonstrate that the period of egg-laying rhythm
      remains unchanged under different ambient temperatures and nutrition levels,
      suggesting that the egg-laying rhythm of D. melanogaster is temperature and
      nutrition compensated. Based on these results, the authors conclude that the egg
      laying rhythm in D. melanogaster is regulated by non-LN(v)-based, non-PDF
      mediated circadian clocks.

PMID- 16461982
TI  - Photic entrainment is altered in the 5-HT1B receptor knockout mouse.
AB  - The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that
      receives glutamatergic afferents from the retina and serotonergic afferents from
      the midbrain. Activation of presynaptic serotonin 1B (5-HT1B) receptors on
      retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and
      light-induced behavioral phase shifts. To assess the role of 5-HT1B receptors in
      photic entrainment, 5-HT1B receptor knockout (5-HT1B KO) and wild-type (WT) mice
      were maintained in non-24 h L:D cycles (T cycles). WT mice entrained to T = 21 h
      and T = 22 h cycles, whereas 5-HT1B KO animals did not. 5-HT1B KO animals did
      entrain to T = 23 h and T = 26 h cycles, although their phase angle of
      entrainment was altered compared to WT animals. 5-HT1B KO mice were significantly
      more phase delayed under T = 23 h conditions and significantly more phase
      advanced under T = 26 h conditions compared to WT mice. When 5-HT1B KO mice were
      housed in a T = 23 h short-day photoperiod (9.5L:13.5D), the delayed phase angle
      of entrainment was more pronounced. Light-induced phase shifts were reduced in 5
      HT1B KO mice, consistent with their behavior in T cycles, suggesting an
      attenuated response to light. Based on previous work, this attenuated response to
      light might not have been predicted but can be explained by consideration of
      GABAergic mechanisms within the SCN. Phase-delayed circadian rhythms during the
      short days of winter are characteristic of patients suffering from seasonal
      affective disorder, and 5-HT has been implicated in its pathophysiology. The 5
      HT1B KO mouse may be useful for investigating the altered entrainment evident
      during this serious mood disorder.

PMID- 16461983
TI  - Effects of food deprivation on locomotor activity, plasma glucose, and circadian
      clock resetting in Syrian hamsters.
AB  - Circadian rhythms in Syrian hamsters can be phase advanced by activity or arousal
      stimulated during the daily rest phase ("subjective day"). A widely used method
      for stimulating activity is confinement to a novel wheel. Some hamsters decline
      to run, and some procedures may reduce the probability of running. The authors
      evaluated food deprivation (FD) as a method to promote running. Given evidence
      that perturbations of cell metabolism or glucose availability may affect
      circadian clock function in some tissues or species, they also assessed the
      effects of FD on free-running circadian phase, resetting responses to photic and
      nonphotic stimuli and plasma glucose. In constant light, a 27-h fast
      significantly increased running in a novel wheel and marginally increased the
      average size of resulting phase shifts. FD, without novel wheel confinement, was
      associated with some very large phase shifts or disruption of rhythmicity in
      hamsters that spontaneously ran in their home wheels during the subjective day.
      Hamsters that ran only during the usual active phase (subjective night) or that
      were prevented from running did not exhibit phase shifts, despite refeeding in
      the mid-subjective day. Using an Aschoff Type II design for measuring shifts, a
      27-h fast significantly increased the number of hamsters that ran continuously
      when confined to a novel wheel but did not affect the dose-response relation
      between the amount of running and the size of the resulting shift. A day of
      fasting also did not affect the size of phase delay or advance shifts to 30-min
      light pulses in the subjective night. Plasma glucose was markedly reduced by
      wheel running in combination with fasting but was increased by running in
      nonfasted hamsters. These results establish FD as a useful tool for stimulating
      activity in home cage or novel wheels and indicate that in Syrian hamsters,
      significant alterations in glucose availability, associated with running,
      fasting, and refeeding, have surprisingly little effect on circadian pacemaker
      function.

PMID- 16461984
TI  - History-dependent changes in entrainment of the activity rhythm in the Syrian
      hamster (Mesocricetus auratus).
AB  - The authors have studied the activity rhythm of Syrian hamsters exposed to square
      LD cycles with a 22-h period (T22) with the aim of testing the effects of the
      previous history on the rhythmic pattern. To do so, sequential changes of
      different lighting environments were established, followed by the same LD
      condition. Also, the protocol included T22 cycles with varying lighting contrasts
      to test the extent to which a computational model predicts experimental outcomes.
      At the beginning of the experiment, exposure to T22 with 300 lux and dim red
      light occurring respectively at photophase and scotophase (LD300/dim red) mainly
      generated relative coordination. Subsequent transfer to cycles with approximately
      0.1-lux dim light during the scotophase (LD300/0.1) promoted entrainment to T22.
      However, a further reduction in light intensity to 10 lux during the photophase
      (LD10/0.1) generated weak and unstable T22 rhythms. When, after that, animals
      were transferred again to the initial LD300/dim red cycles, the amplitude of the
      rhythm still remained very low, and the phases were very unstable. Exposure to
      constant darkness partially restored the activity rhythm, and when, afterwards,
      the animals were submitted again to LD300/dim red cycles, a robust T22 rhythm
      appeared. The results demonstrate history-dependent changes in the hamster
      circadian system because the locomotor activity pattern under the same T22 cycle
      can show relative coordination or unstable or robust entrainment depending on the
      prior lighting condition. This suggests that the circadian system responds to
      environmental stimuli depending on its previous history. Moreover, computer
      simulations allow the authors to predict entrainment under LD300/0.1 cycles and
      indicate that most of the patterns observed in the animals due to the light in
      the scotophase can be explained by different degrees of coupling among the
      oscillators of the circadian system.

PMID- 16461985
TI  - Absence of apparent circadian rhythms of gonadotropins and free alpha-subunit in
      postmenopausal women: evidence for distinct regulation relative to other hormonal
      rhythms.
AB  - Aging is associated with a decrease in gonadotropin levels in postmenopausal
      women (PMW) and is also associated with alterations in a number of circadian
      rhythms. The goals of this study were to determine the presence of circadian
      rhythms of gonadotropins and glycoprotein free alpha-subunit (FAS) in young and
      old PMW. Healthy, euthyroid PMW, ages 45 to 55 years (n = 11) and 70 to 80 years
      (n = 11), were admitted in the morning to start a 24-h constant routine of light,
      temperature, position, and activity. Subjects remained awake and semirecumbent
      for the duration of the study and were fed hourly snacks, and activity was
      monitored continuously. Blood was sampled every 5 min for two 8-h periods
      corresponding to the estimated acrophase and nadir of the temperature rhythm.
      Luteinizing hormone (LH) and FAS were measured in all samples and follicle
      stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and cortisol in 20
      min serum pools. Mean LH (p < 0.001), FSH (p < 0.002), and FAS (p < 0.002) were
      lower in older compared with younger PMW. Day/night differences in cortisol and
      TSH (p < 0.001) were present in all subjects. However, there were no day/night
      differences in LH in younger or older PMW or in FSH in younger or older PMW.
      There were no day/night differences in mean FAS in younger or older PMW or in FAS
      pulse frequency or amplitude. Thus, in controlled studies in which differences in
      cortisol and TSH were demonstrated, there were no day/night differences in LH,
      FSH, or FAS in PMW. These studies suggest that despite evidence of intact
      circadian rhythms of cortisol and TSH, gonadotropin secretion does not appear to
      follow a circadian pattern in PMW. Thus, the age-related decline in gonadotropin
      secretion in PMW is not associated with a dampening of circadian rhythmicity. The
      absence of day/night differences in FAS suggests that GnRH plays a more prominent
      role in FAS regulation than does thyrotropin-releasing hormone in PMW.

PMID- 16461986
TI  - The epidemiology of morningness/eveningness: influence of age, gender, ethnicity,
      and socioeconomic factors in adults (30-49 years).
AB  - The Horne and Ostberg Morningness/Eveningness Questionnaire (MEQ) is widely used
      to differentiate between morning and evening types, but there is very little
      epidemiological evidence about the distribution of MEQ chronotypes in the general
      population. The purpose of the present study was to simultaneously investigate
      the influence of demographic, socioeconomic, and work factors on the distribution
      of morningness/eveningness. A New Zealand version of the MEQ was mailed to 5000
      New Zealand adults, ages 30 to 49 years, who were randomly selected from the
      electoral rolls (55.7% response rate). A total of 2526 questionnaires were
      included in the analyses. According to the Horne and Ostberg classification,
      49.8% of the total population was classified as morning type compared to 5.6%
      having an evening-type preference. However, using new cutoffs for middle-aged
      working adults described by Taillard et al. (2004), 24.7% of the population was
      morning type and 26.4% was evening type. After controlling for ethnicity, gender,
      and socioeconomic deprivation, participants ages 30 to 34 years were more likely
      to be definitely evening type (odds ratio [OR] = 1.59, p < 0.05) and less likely
      to be morning type (moderately morning type, OR = 0.59, p < 0.01, or definitely
      morning type, OR = 0.59, p < 0.05) compared to those ages 45 to 49 years. Work
      schedules were also important predictors of chronotype, with night workers more
      likely to be definitely evening type (OR = 1.49, p = 0.05) and the unemployed
      less likely to be moderately morning type (OR = 0.64, p < 0.05) compared to other
      workers. Evening types were 2.5 times more likely to report that their general
      health was only poor or fair compared to morning types (p < 0.01). This study
      confirms that the original criteria of Horne and Ostberg (1976) are not useful
      for classifying chronotypes in a middle-aged population. The authors conclude
      that morningness/eveningness preference is largely independent of ethnicity,
      gender, and socioeconomic position, indicating that it is a stable characteristic
      that may be better explained by endogenous factors.

PMID- 16461987
TI  - Peripheral gene expression rhythms in a diurnal rodent.

PMID- 16461989
TI  - Pathophysiology of urticaria.
AB  - Urticaria is dermal edema resulting from vascular dilatation and leakage of fluid
      into the skin in response to molecules released from mast cells. The major
      preformed mediator histamine produces a prototypic, short-lived urticaria.
      However, the clinical spectrum and pattern of lesions indicate that other
      molecules, including prostaglandins, leukotrienes, cytokines, and chemokines,
      produced at different times after mast cell activation contribute to the
      polymorphism of this symptom and the variable evolution of this disease. It is a
      common practice to distinguish immunological and nonimmunological urticaria.
      Immunological urticaria is a hypersensitivity reaction mediated by antibodies
      and/or T-cells that results in mast cell activation. Although immunoglobulin
      (Ig)E-mediated type I hypersensitivity (HS) was long postulated to be the major
      immunological pathway associated with mast cell activation, interaction between
      IgE-bound mast cells and allergens is unlikely to be the mechanism by which
      urticaria develops in most patients. It is now well established that urticaria
      may result from the binding of IgG auto-antibodies to IgE and/or to the receptor
      for IgE molecules on mast cells, thus corresponding to a type II HS reaction.
      These auto-immune urticarias represent up to 50% of patients with chronic
      urticaria. Mast cell activation can also result from type III HS through the
      binding of circulating immune complexes to mast cell-expressing Fc receptors for
      IgG and IgM. Finally, under certain circumstances, T-cells can induce activation
      of mast cells, as well as histamine release (type IV HS). Nonimmunological
      urticarias result from mast cell activation through membrane receptors involved
      in innate immunity (e.g., complement, Toll-like, cytokine/chemokine, opioid) or
      by direct toxicity of xenobiotics (haptens, drugs). In conclusion, urticaria may
      result from different pathophysiological mechanisms that explain the great
      heterogeneity of clinical symptoms and the variable responses to treatment.

PMID- 16461990
TI  - Eosinophils and urticaria.
AB  - Previously believed to have an exclusive role in the release of cytotoxic
      mediators in the defense against helminthic infections, eosinophils are now
      considered key players in inflammatory reaction and regulation of immune
      response. Through activation of a large variety of membrane receptors and
      production of various pharmacologically active mediators, eosinophils may exert a
      detrimental role in tissues in which they have been recruited and may contribute
      to the perennization of inflammatory processes. The crucial role of eosinophils
      has been documented in several eosinophilic skin diseases, such as
      hypereosinophilic syndrome and bullous pemphigoid, and the literature provides
      strong evidence for their role in urticaria. The aim of this article is to
      discuss the mechanisms of specific tissue recruitment of eosinophils, the factors
      of eosinophil activation, and the contribution of these cells to inflammation and
      immunoregulation in urticaria. Recent advances in the knowledge of eosinophils
      will certainly help toward developing new strategies for the management of
      antihistamines resistant to urticaria.

PMID- 16461991
TI  - Drug-induced urticarias.
AB  - Drugs may cause urticaria by different mechanisms. The most well-known mechanism
      is the allergic reaction mediated by immunoglobulin (Ig)E antibodies, which
      induce acute generalized urticaria. Allergic reactions to beta-lactams are the
      most common cause of adverse drug reaction mediated by IgE antibodies. However,
      IgE antibodies are not always necessary to activate the release of mediators from
      mast cells and induce acute urticarias. Some drugs, such as opiates or codeine,
      act directly on mast cells, and others, such as aspirin and nonsteroidal anti
      inflammatories, induce an exacerbation of chronic urticaria by a pharmacological
      mechanism involving the arachidonic acid metabolism. Additionally, angioedema is
      a wellknown complication of angiotensin-converting enzyme inhibitors by its
      action on bradykinin, which is a potent vasodilatator agent. Topical drugs, such
      as antibiotics, disinfectants, or anesthetics, may cause urticaria, which
      sometimes progresses to generalized urticaria and, more rarely, to anaphylactoid
      reactions.

PMID- 16461992
TI  - Urticaria and hepatitis.
AB  - Acute urticaria is commonly observed in the prodromic stage of hepatitis A and B
      infection as well as in hepatitis C infection, although only rare cases have been
      published regarding the latter. Urticaria is considered one of the pre-icteric
      symptoms of viral hepatitis and is related to immune-complex deposits;
      subsequently, it may be associated with arthritis and headache (Caroli's triad).
      The absence of specific presentation of acute urticaria in patients with viral
      hepatitis is not surprising because many other viral infections can induce
      similar cutaneous symptoms. On the other hand, no convincing evidence exists in
      which hepatitis virus infection caused chronic urticaria. Data are lacking for
      hepatitis B, but several series and one controlled study showed the absence of a
      link between hepatitis C and chronic urticaria. Systematic hepatitis virus
      investigations in patients with chronic urticaria probably are not cost
      effective. Hepatitis B or C can occasionally induce urticarial vasculitis, but
      this is probably related more to vasculitis than to true urticaria.

PMID- 16461993
TI  - Chronic urticaria and thyroid auto-immunity.
AB  - The association between thyroid auto-immunity and chronic urticaria (CU) has long
      been recognized as significant. The prevalence of antithyroid antibodies (ATAs)
      has been estimated as 12 to 29%. However, most studies have suggested that these
      auto-antibodies are not a direct causative agent in CU. In some patients, ATAs
      are associated with the presence of anti-immunoglobulin E receptor antibodies. It
      appears more likely that these antibodies are associated, parallel, auto-immune
      events. The effects of hormonal treatment on clinical symptoms of CU are
      controversial. They must be evaluated by controlled trials.

PMID- 16461995
TI  - Urticaria and quality of life.
AB  - The common perspective of physicians on chronic urticaria (CU) refers to a benign
      disorder with no pain and no threat to function or life. Heath-related quality-of
      life (HRQOL) tools have demonstrated the extent to which physicians underestimate
      the impact of this disorder. From the patient perspective, CU affects as many
      dimensions of the HRQOL as some life-threatening diseases or well-recognized
      disabling chronic skin disorders, such as psoriasis or atopic dermatitis.
      Pruritus as well as swelling and wheals triggered by unavoidable events, such as
      pressure or sweating, greatly contribute to HRQOL impairment. Recent trials have
      suggested that dermatology-specific HRQOL instruments could be more relevant than
      more objective severity scores when studying and comparing the benefit of various
      therapeutic strategies in chronic idiopathic urticaria.

PMID- 16461994
TI  - Occupational contact urticaria.
AB  - Among contact dermatosis, irritant contact dermatitis and allergic eczema are by
      far the most frequent. Nevertheless, concerning occupational dermatosis, contact
      urticaria should be not neglected. Allergy to natural rubber latex is well-known;
      however, many other substances found in catering jobs and in jobs involving close
      contact with animals or vegetables can cause allergies. Discrete forms are not
      rare and should be remembered during questioning of the patient, as well as
      during a clinical examination. Accordingly, a physician should perform the
      appropriate cutaneous tests--particularly prick tests--and the relevance of these
      tests then needs to be assessed.

PMID- 16461996
TI  - Mastocytosis: the great masquerader.
AB  - Variants of mastocytosis can present with puzzling cutaneous and systemic
      symptoms and signs that can result in an erroneous diagnosis of idiopathic
      urticaria or idiopathic anayphylaxis. The molecular basis of mastocytosis is now
      better understood, with updated classification based on distinct growth factor
      and oncogene abnormalities. Elicitation of a full history and careful attention
      to the skin examination will usually provide the clinician enough information to
      deduce that the condition is not simply chronic idiopathic urticaria.

PMID- 16461997
TI  - Eosinophilic gastroenteritis and citrus-induced urticaria.
AB  - The immunological basis of eosinophilic gastroenteritis (EGE) is an interesting
      contrast between the enigma of urticaria and the increasing usage of molecular
      technology in clinical allergy. Little is known about the natural history of EGE.
      It has been known to spontaneously remit, but the typical course, especially in
      adults, is one of chronic and intermittent disease. Given the often chronic
      nature of this disease, it is important to use relatively benign treatments
      initially and limit the use of systemic corticosteroids. Also, given the fact
      that eosinophilic infiltration of the gastrointestinal tract may also be a
      manifestation of other potentially dangerous disease processes, such as
      malignancy or hypereosinophilic syndrome, which may be initially diagnosed as
      EGE, routine surveillance of the cardiopulmonary and gastrointestinal systems is
      important. We present a patient who demonstrates the variability of presentation
      and treatment response in this multifaceted disease. The fact that he has
      apparently entered remission also makes his an uncommon presentation of EGE.

PMID- 16461999
TI  - A specific CCR3 chemokine receptor antagonist inhibits both early and late phase
      allergic inflammation in the conjunctiva.
AB  - Allergic inflammation manifests as one of a number of diseases, including asthma,
      dermatitis, food allergy, vernal keratoconjunctivitis, and systemic anaphylaxis.
      Together these diseases affect nearly 25% of the Western world and are a leading
      health-care problem. The diseases are often biphasic, with an early phase driven
      primarily by mast cell degranulation and a late phase characterized by leukocyte
      recruitment. While chemokines are well known to be critical for leukocyte
      recruitment, their importance in early-phase reactions is poorly defined. We show
      here that administration of a single oral dose of a high affinity and highly
      selective CCR3 antagonist ablates both the early and late phase reactions in a
      mouse model of allergic conjunctivitis. A direct analysis of mast cells in the
      conjunctiva demonstrates that antagonism of the CCR3 receptor stabilizes the mast
      cell in vivo, thereby leading to the impaired early phase reaction. The late
      phase reaction is also strongly inhibited as characterized by both reduced
      eosinophilia and neutrophilia. These results constitute the first direct evidence
      that antagonism of CCR3 has clear potential for the treatment of allergic
      diseases.

PMID- 16461998
TI  - Regulatory T cell-mediated transplantation tolerance.
AB  - The existence of naturally occurring regulatory T cells in normal hosts and their
      pivotal role in maintaining both auto- and allo-tolerance have direct
      implications on the therapy of autoimmune disorders and for achieving
      immunosuppression-free allotransplantation. Among the various forms of regulatory
      T cells described, CD4(+)CD25(+) T cells have emerged as one of the most potent
      tolerogenic subsets. In this review, we discuss the molecular basis of
      development and function of these regulatory T cells and their potential role in
      the context of chronic lung allograft rejection.

PMID- 16462000
TI  - Role of nitric oxide in mast cells: controversies, current knowledge, and future
      applications.
AB  - Mast cells (MC) are important effector cells in allergic disorders. Recently, the
      role of MC in innate and adaptive immunity is gaining prominence. Nitric oxide is
      an important signaling molecule and its production in mast cell has been reported
      widely. However, controversy exists about whether MC produce NO. This review
      addresses the role of NO in MC biology and the reasons behind the controversy and
      discusses effects of NO in regulation of MC phenotype and function.

PMID- 16462003
TI  - [Childhood trauma in the etiology of borderline personality disorder].
AB  - Serious, prolonged intrafamilial childhood sexual abuse is considered to be the
      main etiological factor in about half of the patients with borderline personality
      disorder in the USA. Special features of childhood interpersonal trauma leading
      to the development of borderline personality disorder are the seriousness of the
      trauma and the fact that it is sexual in nature. Serious intrafamilial childhood
      abuse can lead not only to the classic post-traumatic stress syndrome, but can
      influence all aspects of personality development, including the distortion of the
      sense of identity, self-regulation, and the patterns of interpersonal relations.
      Viewed from the perspective of the trauma concept, the entire range of adult
      borderline symptoms are considered as being the consequences of severe complex
      traumatic experiences. Other clinicians regard such an abuse as a marker of the
      severity of familial dysfunction and emphasize the role of other pathogenic
      factors, such as biparental neglect and biological vulnerability of the pre
      borderline child.

PMID- 16462004
TI  - [Analysis of suicide notes form persons committing completed suicides].
AB  - AIM: The present project is a descriptive research. Our aim was to analyse as
      thoroughly as possible the emotional content of suicide notes left by persons who
      committed suicide. METHOD: Full texts of 250 suicide notes from 182 persons were
      content analysed. In total, we recorded 1375 'content units' in the letters,
      which could be classified into 62 categories. RESULTS: The emotions expressed
      towards acquaintances were rather positive than negative. On the basis of the
      results, we can claim that suicidal persons accuse themselves rather than their
      acquaintances of the suicidal act. The unbearable psychological pain,
      hopelessness, frustrated states, negative self-image, exhaustion and ambivalent
      emotional states all appeared in the letters. CONCLUSION: In our research sample,
      there is a type of suicidal person, who suffers from negative self-image,
      exhaustion, and shows positive emotions towards acquaintances. There is another
      type of person who has narcissistic resentment, sends negative messages towards
      acquaintances, and accuses them for his own suicide.

PMID- 16462002
TI  - Experimental intestinal reovirus infection of mice: what we know, what we need to
      know.
AB  - Reovirus, a member of the Reoviridae family, is a ubiquitous virus in vertebrate
      hosts. Although disease caused by reovirus infection is for the most part mild,
      studies of reovirus have particularly been valuable as a model for understanding
      the local host response to replicating foreign antigen in intestinal and
      respiratory sites. In this article, a brief overview is presented of the basic
      features of reovirus infection, as will the host's humoral and cellular immune
      response during the infectious cycle. New information regarding the interactions
      and involvement of immune response molecules during reovirus infection will be
      presented based on multiple analyte array studies from our laboratory.

PMID- 16462001
TI  - Role of apolipoproteins in gammadelta and NKT cell-mediated innate immunity.
AB  - Recent findings reveal unanticipated connections between the fields of lipid
      metabolism and immunology. They concern gammadelta and NKT cells, nonconventional
      T cell populations that do not recognize protein antigens and are involved in
      immunity against cancer, defense against infections, or in regulation of
      classical immune responses. In this review, we summarize data linking
      perturbations of apolipoprotein levels and nonconventional T cells with
      inflammatory processes such as autoimmune diseases or atherosclerosis. We
      integrate and discuss recent findings on the implication of apolipoproteins in
      antigen recognition by gammadelta and NKT cells, with emphasis on apolipoproteins
      A-I and E. These findings also provide indications that apolipoproteins influence
      antitumor immunosurveillance.

PMID- 16462005
TI  - [Review of the results and developments of the research on suicide notes].
AB  - Suicide notes and diaries of suicidal people give an insight into their thoughts
      and feelings right before their death, therefore, they are valuable tools of
      psychological research. This paper leads through the most important stages of the
      research on suicide notes, which was established by Shneidman and Farberow in the
      1950's. The suicide theory that was developed by them and was further elaborated
      by Ringel and Beck gave inspiration to many remarkable researchers, such as
      Antoon Leenaars and David Lester. Our paper summarises the most important
      tendencies, starting from the analyses of simulated and empirical suicide notes,
      which proved to be a deadlock, and typologies, descriptive analyses (age, gender
      comparisons), , arriving to the latest trends of transcultural application of
      structured framework, and discursive approaches. The discursive approach, which
      was developed in Hungary focuses on the influence that culture and language have
      on suicidal attempts.

PMID- 16462006
TI  - [Comorbidity in child psychiatry: is the comorbidity of pediatric mania and ADHD
      really that high?].
AB  - OBJECTIVE: The purpose of our study was to investigate possible reasons of
      diagnosing comorbidity in child psychiatric disorders, with special attention to
      the comorbidity of mania and attention deficit-hyperactivity syndrome (ADHD).
      METHOD: Using a structured interview, the Mini International Neuropsychiatric
      Interview Kid (M.I.N.I. Kid) we examined 112 consecutive admitted children aged
      under 18 in the Vadaskert Children's Psychiatric Hospital. For all children, best
      estimated diagnoses were made by an independent child-psychiatrist as well, who
      was blind to the diagnoses of the M.I.N.I. Kid. Six children were diagnosed as
      having pervasive developmental disorder by the independent clinician, their data
      were excluded. In this way the data of 106 children were included in the
      statistical analysis. RESULTS: Comorbidity: Based on the M.I.N.I. Kid test
      comorbid diagnoses were found in 74.53% of the children and 51.90% of the
      children with comorbid diagnoses had three or more concomitant diagnoses. The
      maximum number of diagnoses obtained concomitantly by the M.I.N.I. Kid was 9. The
      M.I.N.I. Kid produced 2.58 diagnoses for one child on average. The independent
      child-psychiatrist found comorbid diagnoses in 25.47% of the children. The
      maximum number of diagnoses made by the independent child-psychiatrist for 1
      child was 2. The independent child-psychiatrist established 1.25 diagnoses for
      one child on average. Manic/hypomanic episode: Based on the M.I.N.I. Kid manic
      episode was diagnosed in 14.15% of the children and hypomanic episode in 6,60% of
      them, while the independent psychiatrist did not diagnose these conditions in any
      of the children. 99.33% of the children with manic episode were diagnosed
      together with ADHD by the M.I.N.I. Kid. In 57.14% of those cases, where the
      M.I.N.I. Kid diagnosed a hypomanic episode, it found an ADHD at the same time.
      The independent psychiatrist found ADHD in 73.33% of the children with the
      diagnoses of manic episode and in 57.14% of the children with hypomanic episode
      determined by the M.I.N.I. Kid. CONCLUSIONS: The considerable differences found
      in the number of diagnoses made by using the M.I.N.I. Kid and by the independent
      child psychiatrist may indicate the possible over-sensitivity of structured
      interviews and the characteristics of diagnostic systems: several disorders have
      overlapping symptoms, making the differential diagnoses difficult.

PMID- 16462007
TI  - [Neurocognitive symptoms of childhood attention deficit hyperactivity disorder].
AB  - OBJECTIVES: Attention Deficit Hyperactivity Disorder is the most common childhood
      onset disorder that has been characterized with the dysfunction of executive
      functions. These functions are related to the frontal lobe, especially to
      different frontostriatal networks. The purpose of this study was to examine
      executive functions of 5-7 years old (non-literate) children with and without
      ADHD. METHOD: We used well-known neuropsychological tests (and some other tests
      developed by us) which measure the organisation and execution of behavior and
      thinking. 31 children with ADHD and 26 healthy children without ADHD --
      comparable to the other sample with respect to age and sex -- participated in
      this examination. We compared the two groups in terms of various aspects of
      executive functions, such as inhibition, attention, motor implementation and
      visual memory. The test battery used included the Colour Raven Test, a version of
      the Tower of Hanoi for children, the Bender A and B Test, the Block Design
      Subtest of the Wechsler Intelligence Scale, the children version of Rey Complex
      Figure Test, the Picture Attention Test and the Fruit Stroop Test. In order to
      explore the characteristics of the variables, the factor-analytic method was used
      by which the various aspects of executive functions could be separated. RESULTS:
      Statistical comparison of the two groups revealed that several aspects of
      executive dysfunctions (strategy-constitution, inhibition, attention and motor
      implementation) can be seen in ADHD.

PMID- 16462008
TI  - [Antipsychotic treatment and metabolic syndrome. Consensus meeting of the
      Metabolic Working Group of the Hungarian Diabetes Society and the Hungarian
      Psychiatric Collegium].

PMID- 16462009
TI  - In vivo assessment of coronary artery angioplasty and stent deployment from
      balloon pressure-volume data.
AB  - This study assessed the clinical and practical value of angioplasty balloon
      pressure-volume data, obtained by a computer-controlled balloon inflation device,
      during standard percutaneous coronary intervention (PCI) procedures. Stent
      deployment was studied for 57 lesions in 34 patients. Angiographic predilation
      data were available in 9 patients. Vessel lumen improvement with pre-dilation was
      determined using the area difference under the pressure-volume curves of two
      consecutive inflations and compared to the angiographically determined lumen
      improvement. Stent opening pressure, the inflation volume needed to unfold the
      stent and the shape of the pressure-volume curve were assessed for differences
      between stent sizes (diameter, length) and manufacturer types. A Pearson
      correlation of 0.8 between the pressure-volume area difference and the
      angiographic lumen improvement was significant (p = 0.01), confirming that
      pressure-volume curves are useful in assessing lumen improvement after pre
      dilation. There was a significant difference in stent opening pressure between
      stent types but not between different stent sizes (length, diameter). The
      inflation volume measured during the unfolding process of the stent correlated
      with the calculated stent lumen when deployed (Pearson correlation: 0.65, p =
      0.001). The shape of the pressure-volume curve during stent deployment
      illustrated differences between different stent sizes (length, diameter) during
      inflation. Pressure-volume curves obtained from an automatic balloon inflation
      device have shown their usefulness in providing additional feedback about lumen
      improvement and the mechanical characteristics and quality of stent deployment.

PMID- 16462010
TI  - Time-varying analysis of heart rate variability signals with a Kalman smoother
      algorithm.
AB  - A time-varying parametric spectrum estimation method for analysing non-stationary
      heart rate variability signals is presented. As a case study, the dynamics of
      heart rate variability during an orthostatic test is examined. In this method,
      the non-stationary signal is first modelled with a time-varying autoregressive
      model and the model parameters are estimated recursively with a Kalman smoother
      algorithm. The benefit of using the Kalman smoother is that the lag error present
      in a Kalman filter, as well as in all other adaptive filters, can be avoided. The
      spectrum estimates for each time instant are then obtained from the estimated
      model parameters. Statistics of the obtained spectrum estimates are derived using
      the error propagation principle. The obtained spectrum estimates can further be
      decomposed into separate components and, thus, the time variation of low- and
      high-frequency components of heart rate variability can be examined separately.
      By using the presented method, high resolution time-varying spectrum estimates
      with no lag error can be produced. Other benefits of the method are the
      straightforward procedure for evaluating the statistics of the spectrum estimates
      and the option of spectral decomposition.

PMID- 16462011
TI  - Entropy analysis of the EEG background activity in Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder. Although
      a definite diagnosis is only possible by necropsy, a differential diagnosis with
      other types of dementia and with major depression should be attempted. The aim of
      this study was to analyse the electroencephalogram (EEG) background activity of
      AD patients to test the hypothesis that the regularity of the AD patients' EEG is
      higher than that of age-matched controls. We recorded the EEG from 19 scalp
      electrodes in 11 AD patients and 11 age-matched controls. Two different methods
      were used to estimate the regularity of the EEG background activity: spectral
      entropy (SpecEn) and sample entropy (SampEn). We did not find significant
      differences between AD patients and control subjects' EEGs with SpecEn. On the
      other hand, AD patients had significantly lower SampEn values than control
      subjects (p < 0.01) at electrodes P3, P4, O1 and O2. Our results show an increase
      of EEG regularity in AD patients. These findings suggest that nonlinear analysis
      of the EEG with SampEn could yield essential information and may contribute to
      increasing the insight into brain dysfunction in AD in ways which are not
      possible with more classical and conventional statistical methods.

PMID- 16462012
TI  - Reproducibility of cerebral blood volume measurements by near infrared
      spectroscopy in 16 healthy elderly subjects.
AB  - Near infrared spectroscopy (NIRS) is a non-invasive method to monitor cerebral
      haemodynamics. Used either alone or in combination with other non-invasive
      methods such as transcranial Doppler sonography, this technique is well suited
      for use in cerebrovascular research in ageing. Reproducibility of NIRS, however,
      has only been determined in neonates and adults. We applied controlled
      desaturation (the O(2)-method) to measure the cerebral blood volume (CBV) with
      NIRS in 16 healthy subjects aged 65 to 88. This method uses deoxygenated
      haemoglobin (the concentration of which is manipulated by desaturation) as an
      intravascular tracer for NIRS. We determined repeatability (between tests
      interval: 2 min), short-term reproducibility (intervals of 20 and 40 min) and
      long-term reproducibility (interval > 2 weeks). We found a coefficient of
      variation (CV) of 12.5% for repeatability and a CV of 11.7% for short-term
      reproducibility. The CV for long-term reproducibility was 15%. We conclude that
      NIRS can reproducibly measure CBV in subjects aged 65 and older, using the O(2)
      method. In this group of healthy subjects, this method was well tolerated.

PMID- 16462013
TI  - Gastric impedance spectroscopy in elective cardiovascular surgery patients.
AB  - Impedance spectroscopy has been proposed as a method of monitoring mucosal injury
      due to hypoperfusion and ischemia in critically ill patients. The present study
      characterizes human gastric impedance spectral changes under gastric
      hypoperfusion in patients undergoing cardiovascular surgery, and evaluates
      spectral differences between patients with no evidence of gastric ischemia and
      complications, and patients who developed ischemia and complications. Cole and
      Kun parameters were calculated over time to characterize changes as tissue injury
      progresses. Gastric ischemia was determined by air tonometry. Impedance
      spectroscopy spectra were obtained from 63 cardiovascular surgery patients. The
      recorded spectra were classified into three groups: group 1 for patients without
      ischemia or complications, group 2 for patients with a short period of ischemia
      (less than 2 h) and group 3 for patients with more than 4 h of gastric ischemia
      and complications. Two distinct dispersion regions of the spectra centered at
      about 316 Hz and 215 kHz become clearer as tissue damage develops. The average
      spectrum in group 3 shows a significant difference in tissue impedance at all
      frequencies relative to group 1. The parameters obtained for human gastric tissue
      show significant changes that occur at different times and at different
      frequencies as ischemia progresses, and could be correlated with patient outcome.
      This confirms our hypothesis that hypoperfusion and ischemia cause evident
      changes in the impedance spectra of the gastric wall. Therefore, this technology
      may be a useful prognostic and diagnostic monitoring tool.

PMID- 16462014
TI  - Measurement of gastric emptying by the 13C-octanoate breath test--rationalization
      with scintigraphy.
AB  - The (13)C-octanoate breath test has not achieved universal acceptance for the
      measurement of solid phase gastric emptying, largely because the results are not
      comparable with those from direct methods such as scintigraphy. To convert breath
      test data to their scintigraphic equivalent scale corrections are applied which
      have been obtained from population studies, but there is no guarantee that these
      are applicable in all cases. We propose an alternative method applicable on an
      individual basis based upon a simple physiological model which does not require
      any change to the breath-test protocol. It is demonstrated by comparison with
      scintigraphy and the octanoate saliva test. Results from an existing dataset of
      simultaneous breath test, saliva test and scintigraphic determinations of solid
      phase gastric emptying from nine healthy subjects were re-analysed. The corrected
      breath tests gave gastric emptying curves which were shown to be not
      significantly different to those obtained from scintigraphy. The method provides
      a simple but effective way of generating gastric emptying curves from breath-test
      data that are directly comparable with direct measurement methods, which is
      advantageous since it allows the whole of the gastric emptying profile to be
      generated, not just values for the lag phase and half-emptying times.

PMID- 16462015
TI  - Optimum design of electrode structure and parameters in electrical impedance
      tomography.
AB  - In electrical impedance tomography (EIT) the electrode structure and parameters
      significantly influence measurement sensitivity and image quality, so how to
      optimize the electrode structure and parameters is one of the key problems in
      research today. This paper presents a method to optimize the EIT electrode
      structure and parameters based on coercive equipotential node models. The
      coercive equipotential mode of the compound electrode has been established based
      on that of the line electrode. A simulation study for the line electrode and the
      compound electrode of EIT has been made on a simulation software platform. The
      influences of different electrode structures and parameters on measurement
      sensitivity and the image reconstruction quality are studied. For line electrode
      simulation studies, two important conclusions are drawn. First, a narrower
      electrode is helpful in improving the imaging quality. Second, although it is
      known that a wider electrode is beneficial in decreasing the contact impedance,
      using a too wide electrode causes the measurement sensitivity to decrease.
      Furthermore the electrode width that leads to the best measurement sensitivity is
      different for different measurement depths. The compound electrode has four
      parameters: the excitation electrode width, the measurement electrode width, the
      space between the excitation electrode and the measurement electrode, and the
      distance between two adjacent compound electrodes. These parameters have mutual
      restrictions and complex influences on each other. It is unwise to optimize the
      design of a compound electrode by only using the overlay rate of electrodes. A
      simulation study of EIT electrode structure and parameter influences can be
      carried out according to this paper to determine the optimum design of the
      electrode structure and its parameters.

PMID- 16462016
TI  - Internal versus external intrapartum foetal heart rate monitoring: the effect on
      linear and nonlinear parameters.
AB  - The effect of foetal heart rate (FHR) acquisition mode on linear and nonlinear
      parameters is still largely unknown. In 33 normal labouring women, FHR signals
      were acquired simultaneously by an external ultrasound sensor applied to the
      maternal abdomen and an internal scalp electrode, in the minutes preceding
      delivery. For each case, the initial and final 5, 10 and 20 min segments were
      analysed, considering FHR signals at a frequency of 4 Hz (the frequency at which
      they are transmitted by the majority of commercialized foetal monitors). Several
      time and frequency domain linear and nonlinear FHR indices were computed in these
      segments, namely mean FHR, very low frequency (VLF), low frequency (LF), high
      frequency (HF), approximate entropy (ApEn) and sample entropy (SampEn).
      Parametric confidence intervals, statistical tests and correlation coefficients
      were calculated in order to evaluate the effect of internal versus external FHR
      monitoring modes on the considered indices. The whole evaluation was repeated
      using FHR signals at a frequency of 2 Hz. Most time domain linear indices were
      similar with external and internal monitoring in the initial and final segments
      of the tracings. However, linear frequency domain indices were poorly correlated
      in the final segments and had significantly different mean values in the initial
      segments. Nonlinear indices were significantly different in both initial and
      final segments. The correlation between 4 and 2 Hz sampled parameters was high
      for both linear and nonlinear indices (most correlation coefficient values
      ranging between 0.95 and 1) but nonlinear index values were significantly higher
      at 2 Hz. In conclusion, the mode used to acquire FHR signals and the sampling
      rate employed can significantly affect most FHR indices.

PMID- 16462017
TI  - Limonoids: overview of significant bioactive triterpenes distributed in plants
      kingdom.
AB  - The search for limonoids started long back when scientists started looking for
      the factor responsible for bitterness in citrus which has negative impact on
      citrus fruit and juice industry worldwide. The term limonoids was derived from
      limonin, the first tetranortriterpenoid obtained from citrus bitter principles.
      Compounds belonging to this group have exhibited a range of biological activities
      like insecticidal, insect antifeedant and growth regulating activity on insects
      as well as antibacterial, antifungal, antimalarial, anticancer, antiviral and a
      number of other pharmacological activities on humans. Although hundreds of
      limonoids have been isolated from various plants but, their occurrence in the
      plant kingdom is confined to only plant families of order Rutales and that too
      more abundantly in Meliaceae and Rutaceae, and less frequently in Cneoraceae and
      Harrisonia sp. of Simaroubaceae. Limonoids are highly oxygenated, modified
      terpenoids with a prototypical structure either containing or derived from a
      precursor with a 4,4,8-trimethyl-17-furanylsteroid skeleton. All naturally
      occurring citrus limonoids contain a furan ring attached to the D-ring, at C-17,
      as well as oxygen containing functional groups at C-3, C-4, C-7, C-16 and C-17.
      The structural variations of limonoids found in Rutaceae are less than in
      Meliaceae and are generally limited to the modification of A and B rings, the
      limonoids of Meliaceae are more complex with very high degree of oxidation and
      rearrangement exhibited in the parent limonoid structure. To counter the problem
      of bitterness in citrus juice and products genetic engineering of citrus to
      maximize the formation of limonoid glucosides for reducing limonoid bitterness is
      the focus of recent and future research. Regarding the biological activities of
      limonoids the investigations are to be directed towards detailed
      characterization, quantification, and designing a simple as well as versatile
      synthetic route of apparently important limonoids. Extraction methods too should
      be optimized; evaluation and establishment of pharmaco-dynamic and kinetic
      principles, and structure activity relationships should be a key goal associated
      with limonoids so that they can be safely introduced in our arsenal of
      pharmaceuticals to safeguard the humanity from the wrath of disease and its
      discomfort.

PMID- 16462018
TI  - Low catechol-O-methyltransferase activity in the brain and blood pressure
      regulation.
AB  - Catecholamines (CAs) are important hormones in regulating blood pressure both in
      centrally and peripheral sympathetic nerve endings. Production of CAs, release
      and inactivation are three components to regulate CAs level. We have reported
      that the inactivation of CAs by catechol-O-methyltransferase (COMT) in the liver
      is important in high blood pressure in spontaneously hypertensive rats (SHR). In
      the present study, we investigated central role of COMT in hypertension. We
      investigated COMT activities in cerebral cortex, cerebellum, hippocampus, brain
      stem, hypophysis, and hypothalamus of SHR and Wistar-Kyoto (WKY) rats. COMT
      activities were assessed by measuring normetanephrine with the use of
      norepinephrine as an endogenous substrate. Membrane-bound COMT activities in
      cerebral cortex were significantly reduced in SHR (19.1+/-1.8 pmol/min/mg
      protein) compared with WKY rats (25.0+/-3.3 pmol/min/mg protein). The ratio of
      concentrations of normetanephrine/norepinephrine in cerebral cortex was also
      lower in SHR than in WKY rats. Our results suggest that there is an association
      between MB-COMT in cerebral cortex and blood pressure regulation.

PMID- 16462019
TI  - DNA damage caused by bisphenol A and estradiol through estrogenic activity.
AB  - Evidence exists that raises concern about genotoxic effects induced by estrogen:
      oxidative stress caused by estrogen-derived oxidants, DNA adducts formed by
      estrogen metabolites and estrogen-induced chromosomal aberration. Estrogen
      receptors (ER) participate in some of these genotoxic effects by estrogen. In
      this study, we showed the effects of bisphenol A (BPA), an endocrine-disrupting
      chemical eliciting weak estrogenic activity, and of 17beta-estradiol (E2), on DNA
      damage in ER-positive MCF-7 cells by Comet assay. Higher concentrations of BPA,
      more than 1000 times of E2, were needed to induce the same levels of effects by
      E2. Immunofluorescence microscopy showed that gammaH2AX, an early marker of DNA
      breaks, increased after treatment with E2 or BPA in MCF-7 cells. gammaH2AX foci
      colocalized with Bloom helicase, which is considered to be responsible for the
      repair of DNA damage after treatment with E2 or BPA. Interestingly, DNA damage
      was not as severe in ER-negative MDA-MB-231 cells as in MCF-7 cells. The ER
      antagonist ICI182780 blocked E2 and BPA genotoxic effects on MCF-7 cells. These
      results together suggest that BPA causes genotoxicity ER dependently in the same
      way as E2.

PMID- 16462020
TI  - Anti-asthmatic activity of an ethanol extract from Saururus chinensis.
AB  - As an attempt to find bioactive medicinal herbs exerting anti-asthmatic activity,
      the effects of an ethanol extract from the parts of Saururus chinensis were
      evaluated in both in vitro and in vivo. The ethanol extract of S. chinensis (ESC)
      inhibited generation of the cyclooxygenase-2 (COX-2) dependent phases of
      prostaglandin D(2) in bone marrow-derived mast cells in a concentration-dependent
      manner with an IC(50) value of 14.3 microg/ml. ESC also inhibited leukotriene
      C(4) production with an IC(50) value of 0.3 microg/ml. This demonstrates that ESC
      has COX-2/5-lipoxygenase dual inhibitory activity. In addition, this compound
      inhibited degranulation reaction in a dose dependent manner, with an IC(50) value
      of 1.3 microg/ml. An ovalbumin induced mouse asthmatic animal model was used to
      determine its in vivo anti-asthmatic activity. The oral administration (50-200
      mg/kg) of ESC reduced the number of infiltrated eosinophil in a bronchoalveolar
      lavage fluid. Furthermore, ESC (100 mg/kg) inhibited the eotaxin and IL-4 mRNA
      expression levels. These results suggest that the anti-asthmatic activity of S.
      chinensis might in part occur via the inhibition of eicosanoid generation,
      degranulation as well as the down regulation of IL-4 and eotaxin mRNA expression.

PMID- 16462021
TI  - Decline in glucokinase activity in the arcuate nucleus of streptozotocin-induced
      diabetic rats.
AB  - Glucokinase (GK) is known to be the critical glucose sensor of pancreatic B
      cells. However, the localization and functional role of GK in the brain remains
      to be elucidated. In this study, we measured both the activity and mRNA level of
      GK in the hypothalamic nuclei and the cortex of rats injected intraperitoneally
      with streptozotocin or vehicle. GK activity was measured by a fluorometric assay;
      and the GK mRNA level, by use of the real-time reverse transcription polymerase
      chain reaction. GK activity in vehicle-treated rats was high in the arcuate
      nucleus, moderate or low in the ventromedial nucleus, lateral hypothalamic area,
      and paraventricular nucleus, and very low in the cortex. The order of GK mRNA
      level was almost the same as that of GK activity. GK activity and GK mRNA level
      only in the arcuate nucleus of streptozotocin-treated rats at 7 d, but not at 2
      d, after treatment were lower than those of vehicle-treated rats. The results
      suggest that prolonged hyperglycemia induced by diabetes decreased the activity
      of GK in the arcuate nucleus.

PMID- 16462022
TI  - Andrographolide inhibits the production of TNF-alpha and interleukin-12 in
      lipopolysaccharide-stimulated macrophages: role of mitogen-activated protein
      kinases.
AB  - Andrographolide has been reported to possess a variety of pharmacological
      activities. In this study, we have investigated the effect of andrographolide on
      the production of TNF-alpha and IL-12 (Interleukin-12) in murine peritoneal
      macrophages. Andrographolide decreased TNF-alpha, IL-12a and IL-12b at mRNA
      level, and reduced the production of TNF-alpha and IL-12p70 proteins in a
      concentration-dependent manner. Furthermore, we have found that addition of
      andrographolide inhibited the activation of ERK1/2 MAP kinase, but not that of
      JNK, p38 or NF-kappaB. These results suggested that andrographolide inhibit LPS
      induced production of TNF-alpha via suppression of the ERK1/2 signaling pathway.

PMID- 16462023
TI  - Nuclear localization of the serine/threonine kinase DRAK2 is involved in UV
      induced apoptosis.
AB  - DAP kinase-related apoptosis-inducing kinase 2 (DRAK2), a member of the DAP
      kinase family, is a serine/threonine kinase capable of inducing apoptosis. Here
      we studied the relationship between DRAK2 intracellular localization and
      apoptosis, and found that UV light acts as a stimulus for apoptosis induced by
      DRAK2. The intracellular location of DRAK2 depended on the cell line: DRAK2 was
      found primarily in the nuclei of NRK, NIH3T3, and Caco-2 cells while it was
      present primarily in the cytoplasm of ACL-15, HeLa, and WI-38 cells.
      Overexpression of Myc-tagged DRAK2 led to apoptosis-like cell death in NRK cells,
      but not in ACL-15 cells. A GFP fusion protein of DRAK2 was spontaneously
      localized to the nucleus of ACL-15 cells and resulted in cell death. Nuclear
      localization and cell death were also observed with DRAK2(1-293) fused to the NLS
      of SV40 but not with DRAK2(1-293) alone. These results suggested that nuclear
      accumulation of DRAK2 and the resulting increase in the endogenous level of its
      kinase activity are required for cell death. UV irradiation caused nuclear
      accumulation of endogenous DRAK2 in ACL-15 cells, which was followed by apoptosis
      like cell death. Knockdown of DRAK2 expression by siRNA partially suppressed UV
      induced apoptosis. These results suggest that DRAK2 plays a role in UV induced
      apoptosis.

PMID- 16462024
TI  - Role of polyamines derived from arginine in differentiation and proliferation of
      human blood cells.
AB  - L-Arginine is a precursor of polyamine, nitric oxide (NO), creatine, and agmatine
      and is essential for the differentiation and proliferation of blood cells,
      although the precise biological role of L-arginine is unclear. We have recently
      reported that the depletion of L-arginine in cultured medium prevented both
      proliferation and differentiation of blood cells (Shima et al., Blood First
      Edition Paper, October 6, 2005; DOI 10.1182). Since one of metabolic products of
      L-arginine in the cells is polyamine that associates with cell differentiation
      and proliferation, the effects of L-arginine on the human K562 cell line and
      human cord blood-derived CD34 positive cells were investigated by focusing on
      polyamines such as putrescine, spermidine, and spermine in the present study.
      When polyamines were added to the culture medium in the absence of L-arginine,
      the cells did not grow or differentiate well. However, when intracellular
      polyamines were depleted using ornithine decarboxylase inhibitor, alpha
      difluoromethylornithine (DFMO), the proliferation and differentiation of K562
      cells to erythrocytes were reduced even in the presence of L-arginine. Moreover,
      in the presence of DFMO, cell differentiation and proliferation were recovered by
      the addition of putrescine or spermidine in the presence of L-arginine.
      Accordingly, it was demonstrated that polyamines are essential for the
      proliferation and differentiation of the blood cells as the metabolites of L
      arginine and the externally added polyamines are also effective by being taken up
      through polyamine transporter.

PMID- 16462025
TI  - Candida albicans derived fungal PAMPS, CAWS, water soluble mannoprotein-beta
      glucan complex shows similar immunotoxicological activity with bacterial
      endotoxin from Escherichia coli O9.
AB  - Candida albicans water soluble fraction (CAWS), water soluble fraction of Candida
      albicans mainly composed of mannoprotein-beta-glucan complex, has various
      biological effects, such as anaphylactoid shock and coronary arteritis. These
      toxicological effects fit CAWS as one of PAMPs, pathogen-associated molecular
      patterns. Acute anaphylactoid reaction is known to be induced by
      lipopolysaccharide from Escherichia coli O9 (O9 LPS), which possesses the mannose
      homopolysaccharide as the O-antigen region. In the present study, we compared
      immunotoxicological and immunochemical similarity between CAWS and O9 LPS. CAWS
      strongly reacted with Candida serum factors, and the reactivity was found to be
      partially competed with O9 LPS. CAWS induced lethal toxicity was inhibited by
      pretreatment of mice with i.v. injection of CAWS. The lethality was found to be
      inhibited by i.v. injection of O9 LPS. Vice versa, O9 LPS induced acute lethal
      toxicity was also inhibited by pretreatment of mice with CAWS. These results
      suggested that CAWS, fungal PAMPs, and O9 LPS from Gram-negative bacteria share,
      at least in part, immunochemical and immunotoxicological activities.

PMID- 16462026
TI  - Interaction of intestinal nucleoside transporter hCNT2 with amino acid ester
      prodrugs of floxuridine and 2-bromo-5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole.
AB  - Amino acid ester prodrugs of antiviral and anticancer nucleoside drugs were
      developed to improve oral bioavailability or to reduce systemic toxicity. We
      studied the interaction of human concentrative nucleoside transporter (hCNT2)
      cloned from intestine with various amino acid ester prodrugs of floxuridine
      (FUdR) and 5,6-dichloro-2-bromo-1-beta-D-ribofuranosylbenzimidazole (BDCRB).
      Na(+)-dependent uptakes of [(3)H]-inosine and [(3)H]-adenosine were measured in
      U251 cells transiently expressing intestinal hCNT2. FUdR significantly inhibited
      the uptake of both [(3)H]-inosine and [(3)H]-adenosine (60-70% of control), while
      its amino acid ester prodrugs including Val, Phe, Pro, Asp, and Lys esters
      exhibited markedly decreased inhibition potency (10-30% of control). On the other
      hand, BDCRB and its amino acid prodrugs markedly inhibited the uptake of both
      [(3)H]-inosine and [(3)H]-adenosine. Val, Phe, and Pro ester prodrugs of BDCRB
      showed similar inhibition capacities as parent compound BDCRB (80-90% for
      adenosine and 60-80% for inosine). The amino acid site of attachment (3'- and 5'
      monoesters) and stereochemistry (L- and D-amino acid esters), did not
      significantly affect the uptake of [(3)H]-inosine and [(3)H]-adenosine. These
      results demonstrate that the hCNT2 favorably interacts with BDCRB and its amino
      acid prodrugs, compared to those of FUdR, and that neutral amino acid esters of
      BDCRB have a high affinity toward this transporter. Therefore, the intestinal
      hCNT2 may be a target transporter as a factor for modulating oral
      pharmacokinetics of BDCRB prodrugs.

PMID- 16462027
TI  - Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula,
      on the experimental inflammatory and nociceptive models in rodents.
AB  - JCICM-6, the extract of an anti-arthritic herbal formula composed of medicinal
      herbs of Sinomenium acutum, Aconitum carmichaeli DEBX., Curcuma Longa L., Paeonia
      lactiflora PALL., and Paeonia suffruticosa ANDR., was examined in the
      effectiveness and mechanism in reducing experimentally-induced inflammation and
      nociception using nine animal models. JCICM-6 was extracted from herbs and
      purified with Amberlite XAD-7HP adsorbent resin and analyzed with HPLC
      fingerprint for quality consistency. In acute inflammatory models, the paw edema
      of rats was induced by subcutaneous injection of carrageenan or pro-inflammatory
      mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2)
      (PGE(2)) into the right hind paws of animals; while the ear edema of mice was
      induced by applying arachidonic acid or 12-O-tetradecanoylphorbol 13-acetate
      (TPA) on the ear surface. In nociceptive models, the tail-flick response induced
      by radiant heat stimulation was measured and the numbers of abdominal writhing
      episodes of mice induced by intraperitoneal injection of acetic acid were
      recorded. JCICM-6 orally administered in a range of dosages from 0.438 g to 1.75
      g/kg significantly and dose-dependently suppressed the paw edema of rats induced
      by carrageenan or various pro-inflammatory mediators and the ear edema of mice
      induced by arachidonic acid or TPA. JCICM-6 also significantly prolonged the
      reaction time of rats to radiant heat stimulation and reduced the numbers of
      writhing episodes of mice. These results indicated that JCICM-6 possesses
      significant anti-inflammatory and analgesic effects, which implies that it would
      be a potential candidate for further investigation as a new anti-arthritic
      botanical drug for humans.

PMID- 16462028
TI  - Anxiolytic-like effects of Gastrodia elata and its phenolic constituents in mice.
AB  - The purpose of this study was to characterize the putative anxiolytic-like
      effects of the aqueous extract of the rhizome of Gastrodia elata along with its
      phenolic constituents, 4-hydroxybenzyl alcohol (HA) and 4-hyroxybenzaldehyde
      (HD), using an elevated plus maze (EPM) in mice. The mice were administered
      either the aqueous G. elata extract orally or received an intraperitoneal
      injection of the phenolic constituents, 1 h before the behavioral evaluation in
      the EPM. A single treatment of the aqueous G. elata extract significantly
      increased the percentage of time spent and arm entries into the open arms of the
      EPM versus the saline controls. Among the phenolic constituents of G. elata, HA
      and HD significantly increased the percentage of time spent and arm entries into
      the open arms of the EPM versus saline controls (p<0.05). Moreover, there were no
      changes in the locomotor activity and myorelaxant effects in any group compared
      with the saline controls. In addition, the anxiolytic-like effects of G. elata
      extract were blocked by both WAY 100635 (0.3 mg/kg, i.p.), a 5-HT(1A) receptor
      antagonist, and flumazenil (10 mg/kg, i.p.), a GABA(A) receptor antagonist. The
      anxiolytic-like effects of HA were inhibited by WAY 100635 and the effects of HD
      were antagonized by flumazenil. These results indicate that G. elata is an
      effective anxiolytic agent, and suggests that the anxiolytic-like effects of G.
      elata via the serotonergic nervous system depends on HA and those effects of G.
      elata via the GABAergic nervous system depends on HD.

PMID- 16462029
TI  - Effects of Ginkgo biloba extract feeding on salt-induced hypertensive Dahl rats.
AB  - We previously demonstrated that Ginkgo biloba extract (GBE) produced vasodilation
      via the nitric oxide synthesis and release by increasing the intracellular
      calcium level in vascular endothelial cells of rats. The present study aimed to
      clarify the effects of dietary administration of GBE on the blood pressure and
      vascular tone of hypertensive Dahl salt-sensitive (Dahl) rats in order to
      evaluate its therapeutic actions and availability. Dahl rats were fed an 8.0%
      NaCl diet or an 8.0% NaCl plus 0.5% GBE diet for 24 d. The feeding of GBE did not
      change the heart rate, but significantly decreased systolic blood pressure. After
      24 days' administration, the effects of GBE on the atria and aorta isolated from
      Dahl rats were examined. The GBE-containing diet did not affect the negative and
      positive actions of isolated atria that were produced by acetylcholine and
      isoproterenol, respectively. In the aortic preparations, the relaxation in
      response to acetylcholine was significantly potentiated by a GBE-containing diet.
      Sodium nitroprusside-induced relaxation was unchanged by GBE-containing diet.
      These results demonstrated that GBE reduced salt-related elevation of blood
      pressure and restored the impaired acetylcholine-induced vasodilation in aortic
      segments.

PMID- 16462030
TI  - Enhancement of neuroprotection of mulberry leaves (Morus alba L.) prepared by the
      anaerobic treatment against ischemic damage.
AB  - Several neurological disorders such as Alzheimer's and Parkinson's diseases have
      been attributed to gamma-aminobutyric acid (GABA) depletion in the brain. In
      order to provide a pharmacological basis for the neuroprotective actions of the
      enhanced accumulation of GABA in mulberry leaves (ML) against cerebral ischemia
      in vitro and in vivo, a process was developed to enhance the accumulation of GABA
      in mulberry leaves (GAML) as a result of the various anaerobic treatments. The
      GABA concentrations were changed by N(2) gas purging, the reaction temperature,
      reaction time, pH and the leaf size. GABA enhanced the potential of
      neuroprotection in the PC12 cells damaged by H(2)O(2)-induced oxidation. GAML
      reduced the cytotoxicity in the PC12 cells against oxygen glucose deprivation
      induced cerebral ischemic condition. The neuroprotective effect of GAML was
      further demonstrated in vivo using middle cerebral artery occlusion brain injury
      model. GAML significantly decreased the infarct volume of the brain compared with
      than control group. Overall, these results suggest that the anaerobic treatment
      of ML makes GAML enhance the neuroprotection effect against in vivo cerebral
      ischemia such as in vitro.

PMID- 16462031
TI  - Effects of calcineurin inhibitors on pharmacokinetics of mycophenolic acid and
      its glucuronide metabolite during the maintenance period following renal
      transplantation.
AB  - Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF) has
      been introduced into renal transplant immunosuppressant protocols in combination
      with calcineurin inhibitors (CNIs) and steroids. This study compared the
      pharmacokinetic profiles of MPA and its major metabolite MPA glucuronide (MPAG)
      in combination with tacrolimus (TAC) or cyclosporine (CyA) during the maintenance
      period (>6 months) following renal transplantation. There was no difference
      between TAC and CyA-treated groups in MPA plasma concentration before drug
      administration (C(0)). MPA C(0) in TAC and CyA-treated patients did not differ
      from that in patients who were not treated with a CNI. In patients treated with a
      CNI, MPAG C(0) was significantly greater in those treated with CyA compared with
      TAC. The MPAG/MPA ratio in CyA-treated patients was significantly greater than
      that in the TAC-treated group. We observed that C(0) of MPA was negatively
      correlated with that of TAC and CyA. Positive correlation between MPA C(0), MPAG
      C(0) and serum creatinine was stronger in patients treated with CyA compared with
      TAC. Our study suggests that CyA, but not TAC, inhibits enterohepatic circulation
      of MPAG as a secondary excretion pathway, and that renal function makes a major
      contribution to elimination of MPA and MPAG. We indicate that it may be necessary
      to estimate biliary excretion of MPAG to avoid the risk of intestinal injury in
      patients receiving combination therapy with TAC during the maintenance period.

PMID- 16462032
TI  - Effects of dexamethasone and aminophylline on survival of Jurkat and HL-60 cells.
AB  - The effects of dexamethasone and aminophylline on survival of Jurkat T
      lymphocytic leukemia cells and HL-60 promyelocytic leukemia cells were
      investigated. Dexamethasone (10, 1000 nM) and aminophylline (1, 100 microM)
      induced apoptosis in Jurkat and HL-60 cells in a concentration-dependent manner.
      Treatment with a combination of dexamethasone (10 nM) and aminophylline (1
      microM) significantly increased the number of apoptotic HL-60 cells, but not that
      of Jurkat cells, compared with dexamethasone (10 nM) or aminophylline (1 microM)
      treatment alone. Dexamethasone and aminophylline also increased the number of
      phospho-histone H2B (Ser(14))-positive Jurkat and HL-60 cells. Phospho-histone
      H2B (pH2B)-positive HL-60 cells were significantly increased by treatment with a
      combination of dexamethasone (10 nM) and aminophylline (1 microM), although no
      such effect was observed in Jurkat cells. On the other hand, simultaneous
      treatment with 10 nM dexamethasone and 1 muM aminophylline activated the 36-kDa
      MBP kinase, pro-apoptotic protein kinase in HL-60 cells. The activation of 36-kDa
      MBP kinase by dexamethasone and aminophylline was supported by studies showing an
      increase in the number of pH2B-positive and apoptotic Jurkat and HL-60 cells upon
      exposure to these drugs. Thus treatment with a combination of dexamethasone and
      aminophylline accelerates apoptosis of HL-60 cells via activation of 36-kDa MBP
      kinase and H2B phosphorylation.

PMID- 16462033
TI  - 3-O-(2,3-dimethylbutanoyl)-13-O-decanoylingenol from Euphorbia kansui suppresses
      IgE-mediated mast cell activation.
AB  - Aggregation of the high affinity receptor for IgE (FcepsilonRI) on mast cells by
      antigen and IgE complex induces release of chemical mediators, leading to acute
      allergic inflammation. We recently found that 3-O-(2,3-dimethylbutanoyl)-13-O
      decanoylingenol (DBDI), purified from the Euphorbia kansui L., inhibits
      degranulation in rat basophilic leukemia 2H3 cells upon aggregation of the
      FcepsilonRI. In the present study, we demonstrated that the DBDI significantly
      inhibits release of beta-hexosaminidase, synthesis of eicosanoids, and
      mobilization of intracellular Ca(2+) in the bone marrow-derived mouse mast cells
      stimulated with IgE and antigen. Furthermore, we revealed that phosphorylation of
      Syk, phospholipase C-gamma(2), and extracellular signal-related kinase 1/2 is
      significantly suppressed in the DBDI-treated mast cells. These findings suggest
      that the DBDI may have a therapeutic potential for allergic diseases by
      inhibiting intracellular signaling pathways for activation and chemical mediator
      release in mast cells.

PMID- 16462034
TI  - Effects of Fructus Ligustri Lucidi extract on bone turnover and calcium balance
      in ovariectomized rats.
AB  - The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi
      (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of
      bone turnover, calcium metabolism and balance in osteoporotic rat model developed
      by ovariectomy. Four weeks after surgical operation, animals were randomly
      assigned to one of the four treatments for 14 weeks: sham-operated control
      treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX,
      n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX
      group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and
      urinary deoxypyridinoline levels were upregulated in rats in response to OVX,
      suggesting that the bone turnover rate was accelerated in these animals.
      Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone
      turnover by suppression of both serum osteocalcin (p<0.05, vs. OVX) and urinary
      deoxypyridinoline (p<0.05, vs. OVX) levels. In addition, FLL extract could
      prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium
      absorption rate (p<0.01, vs. OVX), suppressing urinary Ca excretion (p<0.05, vs.
      OVX) as well as increasing bone calcium content (p<0.05, vs. OVX). Our study is
      the first to report that FLL can modulate bone turnover and calcium balance in
      OVX rats and it might be a potential candidate for prevention and treatment of
      postmenopausal osteoporosis.

PMID- 16462035
TI  - Increased GABA transport activity in rat calvarial osteoblasts cultured under
      hyperglycemic conditions.
AB  - Several independent lines of evidence indicate the direct impairment by
      extracellular glucose at high concentrations of different osteoblastic functions
      with a marked decrease in bone mass toward osteoporosis, while the underlying
      mechanisms are not well clarified to date. We have previously demonstrated the
      functional expression of the neural amino acid gamma-aminobutyric acid (GABA)
      signaling system including betaine/GABA transporter-1 (BGT-1) with a temperature
      , sodium- and chloride-dependent activity of [(3)H]GABA accumulation in cultured
      rat calvarial osteoblasts. In this study, therefore, we attempted to demonstrate
      the possible involvement of BGT-1 isoform in bone dysfunctions due to impaired
      mineralization in rat calvarial osteoblasts cultured under hyperglycemic
      conditions. No significant change was seen in [(3)H]GABA accumulation in
      osteoblasts cultured for 7 d in vitro (DIV) under hyperglycemic conditions
      (glucose=25.5-50.5 mM) compared to those cultured in normoglycemic (glucose=5.5
      mM) and hyperosmotic (mannitol=25.5-50.5 mM) conditions. In osteoblasts cultured
      for 14 DIV under hyperglycemic conditions, however, [(3)H]GABA accumulation was
      significantly increased compared to those cultured under normoglycemic and
      hyperosmotic conditions. Kinetic analysis revealed that hyperglycemic cultivation
      resulted in a significant increase in V(max) values from 2.85 nmol/min/mg protein
      for normoglycemic conditions to 4.17 nmol/min/mg protein for hyperglycemic
      conditions without affecting K(m) values. However, experimental hyperglycemia did
      not significantly affect the expression of mRNA for BGT-1 isoform by osteoblasts.
      These results suggest that GABA transport system may at least in part play a role
      in pathological malfunctions and abnormalities through a mechanism not directly
      related to gene expression in osteoblasts under hyperglycemia.

PMID- 16462036
TI  - Glycosidase inhibitory flavonoids from Sophora flavescens.
AB  - The methanol extract of Sophora flavescens showed a potent glycosidase inhibitory
      activity. Active components were identified as well-known flavonoid antioxidants:
      kushenol A (1), (-)-kurarinone (2), sophoraflavanone G (3), 2'-methoxykurarinone
      (4), kurarinol (5), 8-prenylkaempferol (6), isoxanthohumol (7), kuraridin (8) and
      maackian (9). All flavonoids were effective inhibitors of alpha-glucosidase and
      beta-amylase. Interestingly, lavandulylated flavanones 1-5 had strong alpha
      glucosidase inhibitory activities, with IC(50) values of 45 microM, 68 microM, 37
      microM, 155 microM and 179 microM, respectively. Kushenol A (1) which does not
      bear a 4'-hydroxy group showed selective alpha-glucosidase inhibitory activity.
      Lavandulylated chalcone, kuraridine (8), exhibited IC(50) value of 57 microM
      against beta-glucosidase, which is the first report of a chalcone displaying
      glycosidase inhibition. Results showed that 8-lavandulyl group in B-ring was a
      key factor of the glycosidase inhibitory activities. The inhibition pattern was
      noncompetitive for alpha-glucosidase, whereas mixed inhibition was observed for
      beta-amylase.

PMID- 16462037
TI  - Glycoprotein isolated from Acanthopanax senticosus protects against
      hepatotoxicity induced by acute and chronic alcohol treatment.
AB  - The protective effect of a 30 kDa glycoprotein (GF-AS) isolated from the stem
      bark of Acanthopanax senticosus against acute and chronic alcohol-induced
      hepatotoxicity were studied. N-terminal amino acid sequence of GF-AS showed NH(2)
      Val-Ala-Tyr-Pro-Trp-Ala-Gly-Phe-Ala-Leu-Ser-Leu-Glx-Pro-Pro-Ala-Gly-Tyr-. GF-AS
      significantly increases the activities of alcohol-metabolizing enzymes, including
      alcohol dehydrogenase, microsomal ethanol metabolizing system, and acetaldehyde
      dehydrogenase in rats acutely treated with alcohol, resulting in decreased plasma
      alcohol levels. GF-AS also increases the activities of antioxidant enzymes and
      glutathione level. Markers of liver injury induced by alcohol: elevated serum
      levels of aspartate aminotransferase, alanine aminotransferase, triglyceride and
      cholesterol, are reduced by GF-AS in both acutely and chronically treated rats.
      The activities of lipogenic enzymes including malic enzyme, glucose-6-phosphate
      dehydrogenase, and 6-phosphoglucuronic acid dehydrogenase in chronic alcohol
      treated rats are significantly decreased by GF-AS. Furthemore, GF-AS improves
      histological change in fatty liver and hepatic lesions induced by alcohol.
      Collectively, GF-AS may alleviate alcohol-induced hepatotoxicity through
      increasing ethanol and lipid metabolism, as well as antioxidant defense systems
      in livers injured by acute- and chronic-alcohol treatment.

PMID- 16462038
TI  - Identification of medicinal Atractylodes based on ITS sequences of nrDNA.
AB  - Dried rhizomes of five species of Atractylodes (A. japonica, A. macrocephala, A.
      lancea, A. chinensis, and A. koreana), Compositae, have been used as crude drugs
      mainly for the treatment of stomach disorders and for their diuretic properties
      in Chinese and Japanese traditional medicines. The identification of the
      botanical origins of these crude drugs is generally difficult from their
      morphological and chemical features only. In this study, for identification with
      more reliable, nuclear ribosomal DNA (nrDNA), internal transcribed spacer (ITS)
      regions of five species of medicinal Atractylodes were sequenced. As a result,
      specific ITS genotypes were recognized by each species. The four species (A.
      japonica, A. macrocephala, A. lancea, and A. chinensis) prescribed in Chinese and
      Japanese Pharmacopoeias as botanical origins of crude Atractylodes drugs could be
      distinguished by their ITS sequences because they had difference genotypes on the
      ITS sequences. However, the genotype of A. koreana was the same as that of A.
      chinensis. Additionally, hybrids between A. lancea and A. chinensis were also
      recognized as nucleotide additives on their ITS sequences. In this study, several
      morphological characteristics were researched by their genotype, too. As this
      result, the hybrids recognized from the genetic analysis had intermediate
      morphological characteristics between A. lancea and A. chinensis. It was also
      recognized that A. lancea and A. chinensis except for their hybrids were
      significant differences. It is therefore suggested that ITS sequences of nrDNA
      would be useful for the identification of the crude drugs derived from
      Atractylodes species and their interspecific hybridizations.

PMID- 16462039
TI  - Assessment of clonidine orally disintegrating tablet for pre-anesthetic
      medication in pediatric surgery.
AB  - The purpose of this study is to assess orally-disintegrating (OD) tablet of
      clonidine hydrochloride (CL) for a pre-operative sedation in pediatric surgery.
      Sedation score and plasma CL concentration of OD formulation was compared with
      original preparation, CL lollipop, in pediatric patients. Fourteen patients (age:
      3.9+/-2.3 years, weight: 16.9+/-5.0 kg) for OD group and 9 patients (age: 4.4+/
      3.1 years, weight: 17.2+/-7.0 kg) for lollipop group received 4 microg/kg of CL
      preparation. Pre-operative sedation was evaluated by 5-point scoring systems at
      entering the operating room. Plasma CL concentrations were determined 120 min
      after administration of CL preparation. The changes in systolic blood pressure
      (SBP), diastolic blood pressure (DBP) and heart rate (HR) were also assessed
      before and after administration of CL preparation. Every patient in OD group had
      satisfactory sedation (sedation score: 2 and 3), whereas, 3 (33%) in lollipop
      group had unsatisfactory sedation (sedation score: 0 and 1). Plasma CL
      concentration in OD group was significantly higher than those in lollipop group
      (0.75+/-0.15 vs. 0.42+/-0.21 ng/ml, p<0.01). There was no significant difference
      in hemodynamic parameters (SBP, DBP and HR) between before and after
      administration of CL preparation in both OD and lollipop group. We conclude that
      OD is superior preparation of CL for pre-operative sedation in pediatric surgery.

PMID- 16462040
TI  - MDR1 C3435T polymorphism is predictive of later onset of ulcerative colitis in
      Japanese.
AB  - Recently, a silent polymorphism of C3435T of the MDR1 gene, encoding the
      multidrug resistant transporter MDR1/P-glycoprotein, has been found to be
      associated with susceptibility to ulcerative colitis (UC), but this remains
      controversial. This study was conducted to find a possible reason for the
      discrepancies, and it was suggested that the age of onset was important for the
      association, namely, C3435T was predictive of susceptibility to later onset UC,
      but not for early onset UC. Linkage disequilibrium of C3435T with T-129C, C1236T
      and G2677A, T was suggested to be altered in UC, but the analysis of their
      haplotype provided no advantage in terms of prediction over that with only
      C3435T. The effect of C3435T on susceptibility could not be explained by that on
      mRNA expression in rectal mucosa, but it was greater in the C(3435)-noncarriers
      in the early onset group, allowing the individualization of steroid-based
      pharmacotherapy.

PMID- 16462041
TI  - Optimization of suppository preparation containing sodium laurate and taurine
      that can safely improve rectal absorption of rebamipide.
AB  - We previously reported that the fatty base suppository containing sodium laurate
      (C12) and taurine (Tau) (C12-Tau suppository) could enhance the colonic
      absorption of rebamipide, a poorly water-soluble and poorly absorbable drug,
      without any serious mucosal damages in rats. In the preset study, in order to
      make C12-Tau suppositories available for practical use, the scaling-up studies of
      animal and formulation size were performed, compared with the suppositories
      containing sodium caprate (C10) (C10 suppository) at the same amounts as those
      contained in the commercial products. Twenty-mg C12 improved the dissolution of
      rebamipide from suppository remarkably and the addition of 30-mg Tau only
      slightly decreased the dissolution rate. The absorption of rebamipide from rabbit
      rectum was more markedly improved by suppositories containing C12 than C10
      suppositories. Although Tau tended to attenuate the absorption-enhancing effect
      of C12, several C12-Tau suppositories kept high bioavailability values, which
      were much higher than control. Histopathological studies showed that Tau exerted
      the cytoprotective action and that C12-Tau suppositories were better than C10
      suppositories in safety. Considering the balance between efficacy and safety, the
      suppository containing 10- or 20-mg C12 with 30-mg Tau is better than C10
      suppositories as commercial products and could be promising for practical use in
      human.

PMID- 16462042
TI  - Is absorption profile of cyclosporine really important for effective
      immunosuppression?
AB  - The clinical significance of cyclosporine (CsA) concentration 2 h postdose (C(2))
      monitoring is widely recognized in organ transplantation, because C(2) value is
      considered to be a predictable surrogate marker of full area under the
      concentration-time curve (AUC), and/or a peak concentration value exhibits potent
      inhibition of calcineurin activity. However, the pharmacological advantage of
      absorption profile (AP) has not been fully elucidated. In a rat skin
      allotransplantation model, the authors evaluated the efficacy of AP by different
      dosage regimens (20, 25 or 30 mg/kg/d, once or twice daily) and routes (p.o. or
      i.v.), and examined whether high C(2) or AUC(0-4) is intrinsically valuable for
      effective immunosuppression. Graft survival was CsA dose-dependent and correlated
      with full AUC(0-24), rather than AP. The difference between the once and twice
      daily administrations did not influence full AUC(0-24) or immunosuppressive
      effect. Continuous intravenous infusion with flat pharmacokinetics also produced
      adequate immunosuppression as was observed in enteral administration at the same
      level of total exposure. The impact of high peak concentration in AP on
      immunosuppressive effect could not be found. It was suggested that AP would not
      have intrinsic pharmacodynamic value. However, absorption profiling was
      considered to be clinically useful in that C(2) value is a good surrogate marker
      of total exposure (AUC(0-24)).

PMID- 16462043
TI  - The influence of gastric acidity and taste masking agent on in situ gelling
      pectin formulations for oral sustained delivery of acetaminophen.
AB  - Dilute solutions of pectin containing complexed calcium ions form gels when these
      ions are released in the acidic environment of the stomach. The aim of this study
      was to examine the influence of a variation of gastric pH and the addition of a
      taste masking agent on the gelation of the pectin solutions and on the in vitro
      and in vivo release of acetaminophen from the gels. Increase of pH above 2.5 and
      addition of 10% (w/v) D-sorbitol significantly affected the ability of 1.5% (w/v)
      pectin solutions to form coherent gels in vitro. Gelation of sorbitol-free
      formulations was observed at pH 1.2 and in vitro release of acetaminophen from
      the gels followed diffusion-controlled kinetics; in vitro gelation of these
      formulations, however, was incomplete at pH 3.0 resulting in poor sustained
      release characteristics. Inclusion of 10% (w/v) D-sorbitol in the formulations
      inhibited the in vitro gelation of the 1.5% (w/v) pectin sols and poor sustained
      release properties were noted from these formulations even at pH 1.2. The
      bioavailability of acetaminophen from gels formed in the stomach of gastric
      acidity controlled rabbits following oral administration of the liquid
      formulations was not, however, significantly affected either by the inclusion of
      10% (w/v) D-sorbitol or increase of pH to 3.6. Visual observation showed in situ
      gelation of 1.5% (w/v) pectin formulations containing D-sorbitol at pH 4.3
      suggesting that normal variations of gastric acidity in the fasting state will
      have no effect on the bioavailability of acetaminophen when delivered using these
      formulations.

PMID- 16462044
TI  - In vivo nitric oxide production and iNOS expression in X-ray irradiated mouse
      skin.
AB  - Inducible nitric oxide synthase (iNOS) and NO have been suggested to be involved
      in acute radiation response in tissues such as the liver, intestine, colon, and
      brain. However, direct measurement of NO and iNOS in ionizing radiation-induced
      skin inflammatory reactions is not reported yet. We show here for the first time,
      by in vivo experiments, that X-ray irradiated mouse skin generates NO with
      concomitant expression of iNOS at both the mRNA and protein levels. When
      irradiated at 50 Gy, iNOS mRNA appeared at day 8 post-irradiation, whereas iNOS
      protein could be detected only at day 14. No iNOS protein was detectable however
      for the mice receiving 5 or 15 Gy irradiation, even at day 14. Skin inflammatory
      reactions were observed at day 8 post-irradiation as an increase in skin
      thickness, which increased further by day 14. Histological observations showed
      acute inflammatory responses. The parallel relationship between iNOS induction
      and the onset of skin inflammatory reactions suggests the involvement of iNOS and
      NO in the skin damage. Immunohistochemical staining showed the localization of
      iNOS at skin erosion areas, exudate and infiltrating cells. Taken together, these
      findings suggest that iNOS induction and NO production in X-irradiated skin are
      relatively early events in skin inflammatory reactions and are probably secondary
      rather than primary reactions of irradiation.

PMID- 16462045
TI  - Water extract of Cordyceps militaris enhances maturation of murine bone marrow
      derived dendritic cells in vitro.
AB  - Water extract (WE) of Cordyceps militaris has been reported to produce antitumor
      and immunomodulatory activities in vivo and in vitro. However, the therapeutic
      mechanism has not been known. In this study, we investigated whether water
      extract of C. militaris induces the phenotypic and functional maturation of
      dendritic cells (DC). It profoundly increased CD40, CD54, CD80, CD86, and MHC
      class II expression in murine bone marrow (BM)-derived myeloid DC. Endocytosis
      was assessed by the uptake of FITC-dextran and FITC-albumin. The ability of
      unstimulated DC (UT-DC) to uptake dextran and albumin was higher than that of WE-
      or LPS-stimulated DC (LPS-DC). Also, UT-DC secreted a low concentration of IL-12,
      while WE- or LPS-DC secreted higher levels of IL-12 than UT-DC. WE not only
      formed morphologically mature DC and clusters, but also induced predominantly
      functional maturation. Moreover, WE is shown to promote the cytotoxicity of
      specific-cytotoxic T lymphocyte (CTL) induced by DC which were pulsed with P815
      tumor-lysate during the stage of antigen presentation. These results suggest that
      DC maturation by WE can play a critical role in the improvement of the
      immunoregulatory function in patients with impaired host defense.

PMID- 16462046
TI  - Potent analgesic and anti-inflammatory activities of 1-furan-2-yl-3-pyridin-2-yl
      propenone with gastric ulcer sparing effect.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed
      drug for the treatment of inflammation and pain. However, conventional NSAIDs and
      selective COX-2 inhibitors have shown many side effects such as gastric mucosal
      damage and cardiovascular problems. Recently, the use of dual acting inhibitors
      of cyclooxygenases (COX) and lipoxygenase (LOX) has been highlighted for their
      minimized side effects compared to NSAIDs. The objective of the present study was
      to examine the efficacy and the gastric side effects of 1-furan-2-yl-3-pyridin-2
      yl-propenone (FPP-3), a synthetic dual inhibitor of COX/5-LOX. Indomethacin (1-50
      mg/kg, p.o.), a non-selective COX inhibitor, and FPP-3 (0.5-50 mg/kg, p.o.), a
      dual inhibitor, significantly suppressed the carrageen-induced paw edema with
      different pharmacological profiles. The concentrations of FPP-3 and indomethacin
      showing 50% inhibition of the maximum paw edema in rats were 10 mg/kg and 20
      mg/kg, respectively. More importantly, there were no gastric ulcers formed in FPP
      3-treated rats and mice, whereas indomethacin caused gastric mucosal bleeding in
      a concentration-dependent manner. In addition, FPP-3 showed an analgesic effect
      in acetic acid-induced writhing response in mice in a dose-dependent manner. The
      results suggest that FPP-3 may have a benefit in combatting inflammation and pain
      by dual inhibition of COX and LOX.

PMID- 16462047
TI  - Stereospecific effects of ginsenoside Rg3 epimers on swine coronary artery
      contractions.
AB  - Previous reports have shown that ginseng saponins, the active ingredients of
      Panax ginseng, induce relaxation of hormone- or high K(+)-induced blood vessel
      contraction. We recently demonstrated that 20(R)- and 20(S)-ginsenoside Rg(3)
      epimers regulate ion channel activities in a stereospecific manner. Here, we
      examined whether ginsenoside Rg(3) epimers also exhibit differential effects on
      swine coronary artery contractions induced by high K(+) or 5-HT. We found that
      treatment with 20(S)- but not 20(R)-ginsenoside Rg(3) caused a potent
      concentration-dependent, endothelium-independent relaxation of coronary artery
      contraction induced by 25 mM KCl. However, treatment with both 20(S)- and 20(R)
      ginsenoside Rg(3) induced a significant, concentration-dependent relaxation of 3
      microM 5-HT-induced coronary artery contractions in intact samples, while only
      20(S)-ginsenoside Rg(3) inhibited coronary artery contraction in endothelium
      denuded arteries. 20(S)- but not 20(R)-ginsenoside Rg(3) inhibited L-type Ca(2+)
      channel currents in a dose- and voltage-dependent manner. These results indicate
      that 20(S)- and 20(R)-ginsenoside Rg(3) epimers might exhibit stereospecific
      relaxation effects on swine coronary artery contractions caused by high K(+) and
      5-HT receptor activation.

PMID- 16462048
TI  - Oral administration in combination with zinc enhances beta-cryptoxanthin-induced
      anabolic effects on bone components in the femoral tissues of rats in vivo.
AB  - The effects of combined beta-cryptoxanthin and zinc on bone components in the
      femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues of
      rats in vivo were investigated. Rats were orally administered either vehicle,
      beta-cryptoxanthin (5 or 10 microg/100 g body weight), zinc sulfate (0.1 or 0.5
      mg Zn/100 g), or their combination once a day for 7 d. Calcium content, alkaline
      phosphatase activity, and DNA content in the femoral-diaphyseal tissues was not
      significantly altered by the administration of beta-cryptoxanthin (5 microg/100
      g) or zinc (0.1 or 0.5 mg/100 g). Combined administration of beta-cryptoxanthin
      (5 microg/100 g) and zinc (0.1 or 0.5 mg/100 g) caused a synergistic increase in
      calcium content, alkaline phosphatase activity, and DNA content in the diaphyseal
      tissues. The effect of beta-cryptoxanthin (5 or 10 microg/100 g) in increasing
      calcium and DNA contents in the metaphyseal tissues was significantly enhanced by
      the combined administration of zinc (0.1 or 0.5 mg/100 g), but did not have a
      significant effect on the metaphyseal components. The metaphyseal alkaline
      phosphatase activity was markedly increased by the combination of beta
      cryptoxanthin (5 microg/100 g) and zinc (0.1 or 0.5 mg/100 g). This study
      demonstrates that the oral administration of the combination of zinc at lower
      doses synergistically enhances beta-cryptoxanthin-induced anabolic effects on
      bone components in the femoral tissues of rats in vivo.

PMID- 16462050
TI  - Induction of apoptosis by hybrid liposomes for human breast tumor cells along
      with activation of caspases.
AB  - Highly inhibitory effects of hybrid liposomes on the growth of human breast tumor
      cells in vitro were obtained. It is worthy to note that induction of apoptosis
      through activation of caspases by hybrid liposomes was clearly observed.

PMID- 16462049
TI  - Chemoprevention of rat prostate carcinogenesis by diallyl disulfide, an
      organosulfur compound of garlic.
AB  - Diallyl disulfide (DADS), an important component of garlic (Allium sativam) has
      been demonstrated to exert a potential chemopreventive activity against human
      cancers. DADS inhibits proliferation of both androgen dependent and independent
      prostate cancer cells in vitro. However there is no report available on the role
      of DADS on prostate cancer initiation in in vivo model. So the present
      chemoprevention study was conducted to evaluate the activity of diallyl disulfide
      as an anticancer agent in prostate carcinogenesis of male Sprague-Dawley rats.
      Testosterone and N-Methyl N-Nitroso Urea (MNU) were used to induce prostate
      carcinogenesis that involves a multi step process like, hyperplasia, dysplasia
      and prostatic intraepithelial neoplasia (PIN). The rats were induced prostate
      carcinogenesis by injection of testosterone and single dose of MNU and again the
      testosterone was continued throughout the experimental period. Forty percentage
      of animals carried PIN in dorsolateral prostate, while dysplasia and hyperplasia
      (55 to 65%) were common in ventral as well as dorsolateral prostates of the
      hormone and carcinogen treated rats. Rats treated with hormone and carcinogen
      along with DADS developed PIN at incidence of 10% in the ventral and dorsolateral
      prostates about 20 to 10%. Dysplasia and hyperplasia were less common in these
      rats. The results of this study provide evidence that DADS may have
      chemopreventive activity in rat prostate carcinogenesis.

PMID- 16462051
TI  - Human ACAT-1 and ACAT-2 inhibitory activities of pentacyclic triterpenes from the
      leaves of Lycopus lucidus TURCZ.
AB  - Acyl-CoA: cholesterol acyltransferase (ACAT) catalyzes the acylation of
      cholesterol to cholesteryl ester with long chain fatty acids and ACAT inhibition
      is a useful strategy for treating hypercholesterolemia or atherosclerosis.
      Pentacyclic triterpenes, ursolic acid (1), oleanolic acid (2), and betulinic acid
      (3) were isolated from the methanol extracts of the leaves of Lycopus lucidus
      TURCZ. by bioassay-guided fractionation. The structures of compounds 1-3 were
      elucidated by their spectroscopic data analysis. Among them, betulinic acid (3)
      exhibited more potent human ACAT-1 and ACAT-2 inhibitory activities with IC(50)
      values of 16.2+/-0.6 and 28.8+/-1.3 microM, respectively.

PMID- 16462052
TI  - Changes in immune responses to mite antigen sensitized through barrier-disrupted
      skin with CpG-oligodeoxynucleotide in mice.
AB  - CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the
      augmentation of Th1 and suppression of Th2 responses. We examined here the effect
      of CpG-ODN on the immune response to mite antigen sensitized through barrier
      disrupted skin of human atopic dermatitis (AD) model mouse. Although
      sensitization with mite antigen induced Th2-dominant immune response, co
      administration of CpG-ODN elicited Th1-predominant immune response. In terms of
      antigen-specific antibody production, the level of IgG2a was increased by CpG
      ODN, but not in IgE. These results suggested that administration of CpG-ODN via
      skin is a simple strategy for patients with diseases like AD, which is
      characterized by Th2-dominated inflammation.

PMID- 16462053
TI  - Structural changes of cell wall mannans of Candida guilliermondii IFO 10279
      strain cells cultured at high temperature.
AB  - The morphology, structure, and antigenicity of the cells and the cell wall
      mannans of the Candida guilliermondii IFO 10279 strain cultivated at 33 and 34
      degrees C for 48 h in yeast extract-added Sabouraud liquid medium (YSLM) were
      compared with those cultivated at 27 degrees C and 33 degrees C and then at 27
      degrees C (33-27 degrees C). This strain showed little growth at higher than 35
      degrees C. The density of the yeast formed cells decreased, with dry weights of
      about 50% at 33 and 34 degrees C, and only the cells at 34 degrees C revealed a
      failure of cytokinesis. The structure of the mannans revealed by (1)H-NMR
      analysis that the mannans obtained at both 33 and 34 degrees C had drastically
      decreased two consecutive beta-1,2-linked mannopyranose units at the nonreducing
      terminal of the alpha-linked oligosaccharides and increased one beta-1,2-linked
      mannopyranose unit at the nonreducing terminal attached to the alpha-1,3-linked
      mannose unit and the non-reducing terminal alpha-1,3- and alpha-1,2-linked
      mannopyranose units. The enzyme-linked immunosorbent assay (ELISA) showed that
      the mannans obtained at 33 and 34 degrees C had decreased reactivity against the
      factor serum 9 and increased its reactivity against the factor serum 4, in the
      commercially available factor serum kit "Candida Check".

PMID- 16462054
TI  - 5alpha-reductase inhibitory effect of triterpenoids isolated from Ganoderma
      lucidum.
AB  - 5alpha-Reductase inhibitory activity-guided fractionation of the EtOH extract of
      the fruiting body of Ganoderma lucidum (LEYSS.:FR.) KARST. (Ganodermataceae),
      which is called Reishi, or Mannentake in Japan and Lingzhi in China, led to the
      isolation of two active compounds which were ganoderic acid DM and 5alpha-lanosta
      7,9(11),24-triene-15alpha,26-dihydroxy-3-one with an IC(50) of 10.6 microM and
      41.9 microM respectively. A carboxyl group of side chain of ganoderic acid DM is
      essential to elicit the inhibitory activity because of much less activity of its
      methyl ester.

PMID- 16462055
TI  - Chemical constituents of the roots of Piper sarmentosum.
AB  - Sixteen compounds were isolated from the fresh roots of Piper sarmentosum. Seven
      of these have been previously isolated from the fruits and leaves of this plant:
      the aromatic alkene (1), 1-allyl-2-methoxy-4,5-methylenedioxybenzene (4), beta
      sitosterol, pyrrole amide (6), sarmentine (10), sarmentosine (13) and pellitorine
      (14). (+)-Sesamin (2), horsfieldin (3), two pyrrolidine amides 11 and 12,
      guineensine (15) and brachystamide B (16) are new for P. sarmentosum.
      Sarmentamide A, B, and C (7-9) are new natural products. Compounds 1--4 and 6--16
      were tested for antiplasmodial, antimycobacterial and antifungal activities.

PMID- 16462056
TI  - Highly oxygenated guaianolides and eudesman-12-oic acids from Balsamorhiza
      sagittata and Balsamorhiza macrophylla.
AB  - Investigation of lipophilic exudates from the aerial parts of Balsamorhiza
      sagittata and B. macrophylla afforded three new highly oxygenated guaianolides (1
      3), in addition to known guaianolides, germacranolide and eudesmane acids. Their
      chemical structures were elucidated by spectroscopic methods and the data for the
      compounds are reported in Tables 1 and 2 and in Experimental.

PMID- 16462058
TI  - Indoline derivatives I: synthesis and factor Xa (FXa) inhibitory activities.
AB  - A series of bisamidine derivatives each having a ring structure in the center of
      the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were
      evaluated. Among them, some indoline derivatives showed potent inhibitory
      activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2
      position of the indoline ring exhibited the most potent FXa inhibitory activity
      in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent
      anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray
      crystal structure of FXa bound with (R)-18a.

PMID- 16462057
TI  - Characterization and evaluation of silk protein hydrogels for drug delivery.
AB  - The objective of this study was to characterize and evaluate the physicochemical
      properties and drug release profiles of hydrogels composed of silk protein (SP)
      polymers. SPs with a low MW (SPL, ca. 18 kDa) and a high MW (SPH, ca. 76 kDa)
      were used for preparing hydrogels. Both the random coil form and beta-sheet
      conformation simultaneously existed in the hydrogels according to Fourier
      transformed IR determination. Morphologically, the hydrogels showed a sponge-like
      cross-linked structure produced by physical entanglement as well as chemical
      hydrogen and covalent bindings. The in vitro buprenorphine delivery from SPH
      hydrogels showed a slow-release effect, and a zero-order rate was obtained for
      all preparations. Drug release could be controlled by varying the SPH
      concentrations or incorporation of SPL into the systems. SP hydrogels showed a
      stronger barrier property for hydrophilic solutes than for hydrophobic solutes.
      The incorporation of SPH into Pluronic F-127 (PF-127) hydrogels changed the gel
      structure from amorphous micelles to a regularly interconnected texture with
      pores. Furthermore, SPH as an adjuvant polymer in PF-127 and chitosan hydrogels
      lowered and controlled the amount of drug released from those systems.

PMID- 16462059
TI  - Effect of formulated ingredients on rapidly disintegrating oral tablets prepared
      by the crystalline transition method.
AB  - The aim of this article was to determine the optimal ingredients for the rapidly
      disintegrating oral tablets prepared by the crystalline transition method (CT
      method). The effect of ingredients (diluent, active drug substance and amorphous
      sugar) on the characteristics of the tablets was investigated. The ingredients
      were compressed and the resultant tablets were stored under various conditions.
      The oral disintegration time of the tablet significantly depended on diluents,
      due to differences in the penetration of a small amount of water in the mouth and
      the viscous area formed inside the tablet. The oral disintegration time was 10-30
      s for tablets with a tensile strength of approximately 1 MPa, when erythritol,
      mannitol or xylitol was used as the diluent. The increase in the tensile strength
      of tablets containing highly water-soluble active drug substances during storage
      was as large as that of tablets without active drug substances, while the
      increase in the tensile strength of tablets containing low water-soluble active
      drug substances was small. It was therefore found that highly water-soluble
      active drug substances were more suitable for the formulation prepared by the CT
      method than low water-soluble active drug substances. Irrespective of the type of
      amorphous sugar (amorphous sucrose, lactose or maltose) used, the porosity of
      tablets with 1 MPa of tensile strength was 30-40%, and their oral disintegration
      time was 10-20 s. The optimal ingredients for rapidly disintegrating oral tablets
      with reasonable tensile strength and disintegration time were therefore
      determined from these results.

PMID- 16462060
TI  - Physical characteristics of freeze-dried griseofulvin-lipids nanoparticles.
AB  - We have attempted to prepare micronized drug particles and to maintain the
      micronized state long-term in order to improve the solubility of a practically
      insoluble drug, griseofulvin (GF). GF nanoparticles (GFNPs) prepared by high
      pressure homogenization were micronized to about 45 nm (mean particle size).
      GFNPs were subjected to transmission electron microscopy (TEM) observation. The
      mean particle size remained at about 50 nm for 3 months at 25 degrees C. However,
      increased to about 300 nm in 6 months. After 5% (w/v) sugar was added, GFNP was
      freeze-dried and rehydrated. The mean particle size of the rehydrated GFNPs was
      about 160 nm when the sugar was a monosaccharide. In contrast, it was about 55-65
      nm when the sugar was a disaccharide. The powder X-ray diffraction pattern of the
      monosaccharide-containing freeze-dried GFNPs revealed a crystal state of sugar.
      On the other hand, that of the disaccharide-containing freeze-dried GFNPs
      indicated an amorphous state of sugar. From this result, it is considered that
      the high viscosity of an amorphous sugar prevents GFNPs from aggregating through
      retardation of molecular movement. Freeze-dried GFNPs stored for six months at 25
      degrees C showed a good re-dispersibility. After the rehydration the mean
      particle size of GFNPs was 55-65 nm. It was found that freeze-dried GFNPs
      containing sucrose, maltose or trehalose were stable for longer periods than GFNP
      suspensions.

PMID- 16462061
TI  - Three new types of indoloditerpenes, emindole PA-PC, from Emericella purpurea.
      Revision of the structure of emindole PA.
AB  - Three new type indoloditerpenes, emindoles PA (1), PB (2), and PC (3), were
      isolated from the mycelium of Emericella purpurea along with the sesterterpenes
      variecolol and variecolactone, and the dicyanide derivatives epurpurins A to C.
      The structures of 1-3 were confirmed by the spectroscopic investigation. The
      structure of emindoles PA (1) was revised from our preliminary report. Emindoles
      PA (1), PB (2), and PC (3) are the indoloditerpenes having a new type of carbon
      skeleton.

PMID- 16462062
TI  - Control release effects of binders used in pills of traditional Chinese medicine
      herbs.
AB  - This research investigated the effects of control release of binders that are
      used in the pills of Chinese herbal medicine, namely, as processed honey, starch
      paste, beeswax, or mixtures thereof. Aspirin and baicalin were used as the active
      pharmaceutical ingredients (API). The processed honey was heated to 110 degrees
      C, 120 degrees C, or 130 degrees C. In these pills, the binders were the only
      excipients. The pills were prepared by the stir method using a mixer at 80
      degrees C without pressure. The differential thermal analysis (DTA) showed that
      the melting points of aspirin and baicalin were changed by the binders. The
      Fourier Transform infrared spectra (FT-IR) of aspirin and baicalin suggest that
      there are different non-covalent molecular interactions between the API and the
      binders, such as C-H-pi and hydrogen bond interaction. The dissolution profiles
      indicate that changing the ratio of the binders altered the patterns of
      dissolution of the API; thus, this ration may be used to control the release of
      API from the pills.

PMID- 16462063
TI  - Expeditious syntheses of conjugated allenyl esters and oxazoles through a cascade
      reaction of alpha-alkynyl malonates under alkaline conditions.
AB  - Diethyl alpha-alkynyl-alpha-methoxymalonates (2a--e) were smoothly hydrolyzed and
      then decarboxylated under alkaline conditions employing 1 N KOH in EtOH to give
      conjugated allenyl esters (6a--e) in high yields, and similar alkaline treatment
      of diethyl alpha-alkynyl-alpha-acetylaminomalonates (5a, b, d, e) furnished
      unexpectedly the oxazoles (7a, b, d, e) having three substituent groups in
      excellent yields.

PMID- 16462064
TI  - Synthesis of 5(6H)-phenanthridones using Diels-Alder reaction of 3-nitro-2(1H)
      quinolones acting as dienophiles.
AB  - Diels-Alder reactions of 3-nitro-2(1H)-quinolones with 1,3-butadiene derivatives
      were carried out to give the phenanthridone derivatives under both atmospheric
      and high pressure conditions. Furthermore, the reactivity of 3-substituted 2(1H)
      quinolones acting as a dienophile with 2,3-dimethyl-1,3-butadiene was examined
      using molecular orbital (MO) calculation.

PMID- 16462065
TI  - Novel Diels-Alder reaction of 4-nitro-1(2H)-isoquinolones.
AB  - A novel Diels-Alder (DA) reaction with 4-nitro-1(2H)-isoquinolones acting as the
      dienophile afforded 5(6H)-phenanthridone derivatives. The DA reaction of 4-nitro
      1(2H)-isoquinolone with 1-methoxy-1,3-butadiene gave biologically active 5(6H)
      phenanthridone possessing in a high yield. Regioselectivity of 4-nitro-1(2H)
      isoquinolones with 1-methoxy-3-silyloxy-1,3-butadiene was calculated using
      molecular orbital (MO) calculations.

PMID- 16462066
TI  - Constituents of Caesalpinia crista from Indonesia.
AB  - Ten new furanocassane-type diterpenes named, caesalpinins H-P (1-9) and
      norcaesalpinin F (10), were isolated from the CH(2)Cl(2) extract of the seed
      kernels of Caesalpinia crista, together with 13 known diterpenes. Their
      structures were determined based on the spectroscopic analysis. Among the
      isolated compounds, caesalpinin N (7) represents the first example of
      furanocassane-type diterpene possessing an aldehyde group at C-14.

PMID- 16462067
TI  - Two new sesquiterpene polyesters from the seeds of Euonymus nanoides LOES.
AB  - Two new beta-dihydroagarofuran sesquiterpene polyesters, 1S,13-diacetyloxy-4S
      hydroxy-6R-(3-)furancarbonyloxy-9S-cinnamoyloxy-beta-dihydroagarofuran (1) and
      1S,6R-di(2-)methylbutanoyloxy-4S-hydroxy-8S-benzoyloxy-9R-(3-)furancarbonyloxy-13
      acetyloxy-beta-dihydroagarofuran (2), together with one known compound (3) were
      isolated from the seeds of Euonymus nanoides LOES. Their structures were
      elucidated by spectroscopic data interpretation. Compound 2 showed moderate
      antitumor activity against BEL-7402, P-388, HL-60 and A-549.

PMID- 16462068
TI  - The essential oil constituents and antimicrobial activity of Anthemis aciphylla
      BOISS. var. discoidea BOISS.
AB  - The essential oil of aerial parts, leaves and flowers of the endemic Anthemis
      aciphylla BOISS. var. discoidea BOISS. (Asteraceae) were obtained by
      hydrodistillation. The oils were analyzed both by GC and GC-MS on a polar column.
      The monoterpenes alpha-pinene (9-49%) and terpinen-4-ol (22-32%) were
      characterized as the main constituents. An unknown component isolated from the
      essential oil was characterized by means of MS, HR-MS, FT-IR, 1D- and 2D-NMR
      techniques as isofaurinone (1). Furthermore, the biological activity of the
      essential oils was evaluated in various human pathogenic microorganisms using the
      broth microdilution method. Weak to moderate inhibitions (0.06-1.0 mg/ml) was
      observed.

PMID- 16462069
TI  - Synthesis of lyoniresinol with combined utilization of synthetic chemistry and
      biotechnological methods.
AB  - We have synthesized lyoniresinol with the combined utilization of synthetic
      chemistry and biotechnological methods, specifically using plant cell cultures as
      an "enzyme source."

PMID- 16462070
TI  - Steroidal glycosides from the underground parts of Solanum sodomaeum.
AB  - A new steroidal glycoside has been isolated from the underground parts of Solanum
      sodomaeum L., along with seven known steroidal glycosides. Their chemical
      structures were determined on the basis of spectroscopic data and chemical
      evidence, and the structure of one known pregnane type glycoside was corrected.
      In addition, their antiproliferative activity against human promyelocytic
      leukemia (HL-60) cells was investigated, and five compounds exhibited stronger
      activity than cisplatin.

PMID- 16462071
TI  - Three new flavonol glycosides from the aerial parts of Rodgersia podophylla.
AB  - Three new flavonol glycosides were isolated together with five known flavonoids
      and six bergenin derivatives from the aerial parts of Rodgersia podophylla. The
      structures of these new compounds were elucidated by spectral methods as
      kaempferol-3-O-alpha-L-5''-acetyl-arabinofuranoside (1), kaempferol 3-O-alpha-L
      3''-acetyl-arabinofuranoside (2), and quercetin-3-O-alpha-L-3'',5''-diacetyl
      arabinofuranoside (3).

PMID- 16462072
TI  - Steroidal alkaloid glycosides, esculeosides C and D, from the ripe fruit of
      cherry tomato.
AB  - Two new steroidal alkaloid glycosides, esculeosides C and D, have been isolated
      from the ripe fruit of Cherry tomato [Lycopersicon esculentum var. cerasiforme
      (DUNAL) ALEF.], along with three known steroidal alkaloid glycosides, esculeoside
      A, esculeoiside B, and lycoperoside G. Their chemical structures were determined
      on the basis of spectroscopic data.

PMID- 16462073
TI  - Bacosterol glycoside, a new 13,14-seco-steroid glycoside from Bacopa monnieri.
AB  - A new sterol glycoside, bacosterol-3-O-beta-D-glucopyranoside along with
      bacopasaponin-C, bacopaside-I, bacopaside-II, bacosterol, bacosine and luteolin-7
      O-beta-glucopyranoside have been isolated from Bacopa monnieri. Their structures
      were elucidated mainly on the basis of IR, 1D, 2D NMR (HMQC, HMBC, COSY), HR-ESI
      QTOF-MS and EI mass spectral studies.

PMID- 16462074
TI  - Enhanced delivery of retinoic acid to skin by cationic liposomes.
AB  - We studied the delivery of retinoic acid to skin by using cationic liposomes
      consisting of double-chained cationic surfactant, phosphatidylcholine (PC) and
      retinoic acid in excised guinea pig dorsal skin. Egg yolk PC liposomes contaning
      retinoic acid at a molar ratio of 4 : 1 increased the delivery of retinoic acid
      about two-fold, compared with its addition as an isopropyl myristate solution.
      Cationic liposomes containing 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)
      further enhanced the incorporation dependent on the DOTAP content. Liposomes
      consisting of DOTAP, egg yolk PC, and retinoic acid at a molar ratio of 2 : 2 : 1
      induced a 3.7-fold increase in the skin incorporation compared with the egg yolk
      PC liposomes without DOTAP. Significant difference was not observed when either
      dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC)
      was used instead of egg yolk PC as well as when dimethyldipalmitylammonium was
      used instead of DOTAP. These results suggest the potential of the use of the
      cationic liposomes for the intradermal delivery of lipophilic drugs like retinoic
      acid.

PMID- 16462075
TI  - Labeling of acetaminophen with I-131 and biodistribution in rats.
AB  - The aim of the present study was to label acetaminophen (APAP) with I-131 and to
      determine its radiopharmaceutical potential in rats. Acetaminophen was labeled
      with I-131 using the iodogen method. The radiochemical purity of (131)I-APAP was
      determined by RTLC and paper electrophoresis. The labeling yield was 94 +/- 4%.
      The biodistribution studies of the labeled compound (specific activity; 56.60
      GBq/mmol) were performed in male Albino Wistar rats. The uptake of (131)I-APAP in
      some organs were determined at different time after injection to the rats. The
      radioactivity in each organ was counted and the percentage of injected activity
      per gram of tissue weight (%ID/g) for each organ and blood was calculated. (131)I
      APAP uptake in the lung, liver, kidneys, pancreas, blood, stomach and some brain
      region, were observed. Thus, (131)I-APAP may be radiopharmaceutical for the
      imaging of the brain.

PMID- 16462076
TI  - Study on the synthesis and cytotoxicity of new quinophenoxazine derivatives.
AB  - We have synthesized several new quinophenoxazine analogues and tested their
      cytotoxicity activities. The results showed that the compounds, 4a and 4b,
      possessing phenyl ring in the structure have almost same pharmacological capacity
      with A-62176. This finding suggests that the phenyl ring portion is important to
      this series of compounds for the activity expression.

PMID- 16462077
TI  - Rossicasins A, B and rosicaside F, three new phenylpropanoid glycosides from
      Boschniakia rossica.
AB  - Three phenylpropanoid glycosides have been isolated, together with the known
      phenylpropanoid glycosides rossicaside A (4), B (5), E (6), and trans-p-coumaryl
      alcohol 1-O-beta-D-glucopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->3)-beta-D
      glucopyranoside (7), and an acylated oligosaccharide beta-D-glucopyranosyl(1-->4)
      alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-D-glucopyranose) (8), from
      the aqueous extract of Boschniakia rossica (CHAM. et SCHLECH.) FEDTSCH. et
      FLEROV. Spectroscopic evidence led to the assignments of their structures as
      trans-p-coumaryl-(6'-O-beta-D-xylopyranosyl)-O-beta-D-glucopyranoside (1), trans
      p-coumaryl-(6'-O-alpha-L-arabinopyranosyl)-O-beta-D-glucopyranoside (2) and 2
      (3,4-dihydroxyphenyl)-R,S-2-ethoxy-ethyl-O-beta-D-glucopyranosyl(1-->4)-alpha-L
      rhamnopyranosyl(1-->3)(4-O-trans-caffeoyl)-beta-D-glucopyranoside (3), designated
      as rossicasin A, rossicasin B, and rossicaside F, respectively. Compound 7 was
      identified from the degradation reaction and this is the first isolation from a
      natural source.

PMID- 16462078
TI  - Simultaneous qualitative and quantitative analyses of the major constituents in
      the rhizome of Ligusticum Chuanxiong using HPLC-DAD-MS.
AB  - An HPLC-DAD-MS method was developed for the qualitative and quantitative analysis
      of the major constituents in Chuanxiong (the dried rhizome of Ligusticum
      chuanxiong Hort). Twenty compounds including phenolic constituents,
      alkylphthalides and phthalide dimers were identified using online ESI-MS and
      comparisons with literature data and standard compounds, and six of them were
      quantified by HPLC-DAD simultaneously. A comprehensive validation of the method
      including sensitivity, linearity, repeatability and recovery was conducted. The
      linear regressions were acquired with R(2) > 0.99 and limit of detection (LOD,
      S/N = 3) values were between 1.5 and 2.5 ng. The repeatability was evaluated by
      intra- and inter-day assays, and relative standard deviation (RSD) values were
      reported within 1.87%. The recovery studies for the quantified compounds were
      observed in the range of 96.36-102.37% with RSD values less than 2.63%. These
      phenolic constituents and alkylphthalides, the major constituents in Chuanxiong,
      are generally regarded as the index for the quality assessment of this herb. The
      overall procedure is accurate and reproducible, which is considered suitable for
      the qualitative and quantitative analyses of a large number of Chuanxiong
      samples.

PMID- 16462079
TI  - Isolation and structure of a galactocerebroside molecular species from the
      starfish Culcita novaeguineae.
AB  - A galactocerebroside molecular species, CNC-2, has been isolated from the less
      polar lipid fraction of a chloroform/methanol extract of the starfish Culcita
      novaeguineae. The structure of this galactocerebroside molecular species was
      determined on the basis of chemical and spectroscopic evidence. CNC-2 is a
      phytosphingosine-type galactocerebroside molecular species with nonhydroxylated
      and hydroxylated fatty acyl moieties. The isolation of a galactocerebroside from
      echinoderms is rare.

PMID- 16462080
TI  - COX-1, COX-2 inhibitors and antifungal agents from Croton hutchinsonianus.
AB  - Two new compounds, 3'-(4''-hydroxy-3'',5''-dimethoxyphenyl)-propyl benzoate (1)
      and 3'-(4''-hydroxyphenyl)-propyl benzoate (3) together with known compounds, 3'
      (4''-hydroxy-3''-methoxyphenyl)-propyl benzoate (2), poilaneic acid (4), farnesyl
      acetone (5) and 4-hydroxybenzaldehyde (6) were isolated and identified from the
      branches of Croton hutchinsonianus. Their structures were determined by
      spectroscopic methods. The three phenylpropyl benzoates (1-3) were found to
      exhibit antifungal activity against Candida albicans (IC(50) 5.36-11.41
      microg/ml). Compounds 1-2 (IC(50) 2.11-4.95 microg/ml) exhibited potent but non
      selective activity against the enzymes cyclooxygenase-1 (COX-1) and
      cyclooxygenase-2 (COX-2) whereas 3 (IC(50) 1.88 microg/ml) preferentially
      inhibited the enzyme COX-2.

PMID- 16462081
TI  - Cytotoxic polyprenylated xanthones from the resin of Garcinia hanburyi.
AB  - Thirteen xanthones (1-13) were isolated from the resin of Garcinia hanburyi.
      Among them, two new compounds (namely gaudichaudic acid, and isogambogenic acid,
      1, 2), and one new natural product (deoxygaudichaudione A, 3) were identified on
      the basis of extensive spectral evidence including detailed 2D NMR data. Ten of
      these xanthones were tested for their cytotoxicities against human leukemia K562
      (K562/S) and doxorubicin-resistant K562 (K562/R) cell lines, and showed similar
      inhibitory effects on both cell lines, suggesting that this group of
      polyprenylated xanthones might not be multidrug resistance (MDR) substrates.

PMID- 16462082
TI  - PLA2 inhibitory activity of marine sesterterpenoids cladocorans, their
      diastereomers and analogues.
AB  - Inhibition of secretory phospholipase A(2) (sPLA(2)) by cladocorans A and B and
      their diastereomers almost equaled that of manoalide.

PMID- 16462083
TI  - Isolation and absolute configuration determination of aliphatic sulfates as the
      Daphnia kairomones inducing morphological defense of a phytoplankton.
AB  - 2,6-Dimethylheptyl sulfate (1) and 6-methyloctyl sulfate (3) were isolated from
      Daphnia pulex as the Daphnia kairomones that induced morphological defense of a
      freshwater phytoplankton Scenedesmus gutwinskii var. heterospina (NIES-802). The
      absolute stereochemistry at C2 of 1 was determined by (1)H-NMR analysis of the
      (R)-MTPA ester of alcohol 2. The absolute configuration at C6 of 3 was determined
      by Ohrui's method applied to alcohol 4.

PMID- 16462084
TI  - Two phenylpropanoid glycosides from Neopicrorhiza scrophulariiflora.
AB  - Two new phenylpropanoid glycosides, scrophulosides A (1) and B (2), were isolated
      from the rhizomes of Neopicrorhiza scrophulariiflora (Scrophulariaceae), along
      with two known compounds, androsin (3) and picroside I. Their structures were
      elucidated on the basis of both chemical and spectroscopic data.

PMID- 16462085
TI  - Larvicidal, antimycobacterial and antifungal compounds from the bark of the
      Peruvian plant Swartzia polyphylla DC.
AB  - The 95% ethanol extract of the bark of Swartzia polyphylla DC (Fabaceae)
      possesses important larvicidal, antimycobacterial and antifungal activity in
      vitro. Bioassay-guided studies performed on the crude ethanol extract afforded T
      cadinol as the larvicidal and anti-Mycobacterium tuberculosis principle, while
      the antifungal activity of the extract is due to the presence of the flavonoids
      biochanin A and dihydrobiochanin A.

PMID- 16462086
TI  - [Abnormal ryanodine receptor function in heart failure].

PMID- 16462087
TI  - [Aldosterone in heart failure].

PMID- 16462088
TI  - [Cell cycle and heart failure].

PMID- 16462089
TI  - [Role of endoplasmic reticulum stress in hypertrophic and failing hearts].

PMID- 16462090
TI  - [Promotion of a banking system for human tissue in the providing medical
      institution].

PMID- 16462091
TI  - [Visualizing exocytosis of insulin granules with total internal reflection
      fluorescence microscopy].

PMID- 16462092
TI  - [Pharmacological characteristics and clinical efficacy of bosentan].

PMID- 16462093
TI  - [Pharmacological and clinical profile of anti-human IL-6 receptor antibody
      (tocilizumab, ACTEMRA), a novel therapeutic drug for Castleman's disease].

PMID- 16462094
TI  - Analysis of the promoter of mutated human whey acidic protein (WAP) gene.
AB  - Although whey acidic protein (WAP) has been identified in the milk of a range of
      species, it has been predicted that WAP is not secreted into human milk as a
      result of critical point mutations within the coding region. In the present
      study, we first investigated computationally the promoter region of mutated human
      WAP genes by comparing with those of other known WAP genes. Computational
      database analyses showed that the human WAP promoter region was highly conserved,
      as in other species with milk WAP. Next, we evaluated the activity of the human
      WAP promoter (2.6 kb) using a reporter gene assay. MCF-7 cells were stably
      transfected with the hWAP/hGH (human growth hormone) fusion gene, cultured on
      Matrigel, and treated with lactogenic hormones. Radioimmunoassay detected hGH in
      the culture medium, indicating that the human WAP promoter was responsible for
      the lactogenic hormones. The human WAP promoter was significantly more active in
      MCF-7 cells than the mouse WAP promoter (2.4 kb). The present results provide us
      with important information on the molecular evolution of milk protein genes.

PMID- 16462095
TI  - Relationship between time elapsed after human chorionic gonadotropin
      administration and developmental stage in porcine embryos collected from
      prepubertal gilts.
AB  - We examined the relationship between the time elapsed after human chorionic
      gonadotropin (hCG) administration and developmental stage of porcine embryos
      after collection. Prepubertal gilts, 7 to 8 months old, were given 1500 IU equine
      chorionic gonadotropin (eCG) intramuscularly, followed by 500 IU hCG 72 h later.
      The treated gilts were inseminated artificially on Day 1 (Day 0=the day of hCG
      administration) and on Day 2. Embryos were collected surgically on Day 6 (140,
      144, and 147 h after hCG administration) or on Day 7 (164, 168, and 171 h), and
      the developmental stages of the collected embryos were examined. From 75.2%
      (276/367) of the prepubertal gilts treated with hormones, we collected an average
      of 20.7 embryos per gilt with normal morphology. At 140 h after hCG
      administration, morulae (54.4%) could be collected. At 144 h, morulae and early
      blastocysts (57.7% and 28.9%, respectively) were collected. By 147 h, the
      proportion of embryos at the blastocyst to expanded blastocyst stages had
      increased (10.0%). From 164 h to 171 h, expanding or expanded blastocysts of more
      than 200 microm in diameter and hatched blastocysts could be collected. The
      proportion of hatched blastocysts increased from 3.2% (164 h) to 41.0% (171 h).
      These results suggests that although the number of ovulations differed among
      gilts, porcine embryos at the appropriate stages can be collected efficiently by
      controlling the time elapsed between hCG administration and embryo collection.

PMID- 16462096
TI  - [Endogenous cannabinoid receptor ligands--anandamide and 2-arachidonoylglycerol].
AB  - Marijuana has been used as a traditional medicine and a pleasure-inducing drug
      for thousands of years around the world, especially in Asia. Delta(9)
      tetrahydrocannabinol, major psychoactive component of marijuana, has been shown
      to interact with specific cannabinoid receptors, thereby eliciting a variety of
      pharmacological responses in experimental animals and human. In 1990, the gene
      encoding a cannabinoid receptor (CB1) was cloned. This prompted the search for
      endogenous ligands. In 1992, N-arachidonoylethanolamine (anandamide) was isolated
      from pig brain as an endogenous ligand, and in 1995, 2-arachidonoylglycerol was
      isolated from rat brain and canine gut as another endogenous ligand. Both
      anandamide and 2-arachidonoylglycerol exhibit various cannabimimetic activities.
      The results of structure-activity relationship experiments, however, revealed
      that 2-arachidonoylglycerol, but not anandamide, is the intrinsic natural ligand
      for the cannabinoid receptor. 2-arachidonoylglycerol is a degradation product of
      inositol phospholipids that links the function of the cannabinoid receptors with
      the enhanced inositol phospholipid turnover in stimulated tissues and cells. The
      possible physiological roles of cannabinoid receptors and 2-arachidonoylglycerol
      in various mammalian tissues such as those of the nervous and inflammatory cells
      are demonstrated. Furthermore, the future development of therapeutic drugs coming
      from this endocannabinoid system are discussed.

PMID- 16462097
TI  - [Subject making and evaluation method for objective structured clinical
      examination (OSCE) in pharmaceutical practice].
AB  - The aim of this study was to discuss subject selection and the evaluation method
      for an objective structured clinical examination (OSCE) in pharmaceutical
      sciences. We designed the OSCE to assess pharmaceutical students' clinical
      ability. In this trial, there are three stations (ST1 in circle: dispensing
      powdered medicine, ST2 in circle: patient reception, ST3 in circle: drug
      counseling), and 25 students and six instructors participated. Each student took
      an examination at two stations, and evaluated other students at the other
      station. Each instructor evaluated the student at two stations. Before the
      evaluation, we developed a checklist that contained the items "evaluation of the
      quantity" of the action, "evaluation of the quality" of the skill and the
      attitude, and "overall evaluation" to ensure the standardization of scoring.
      After the OSCE trial, we calculated and analyzed each examinee's evaluation
      score. In ST1 in circle and ST3 in circle, the average time for performance
      exceeded the time limit (5 min). There was no significant relationship between
      the each examinee's evaluation score and the time at all stations. The evaluation
      point "evaluation of the quantity" did not differ among evaluators, but a
      difference was seen in the "evaluation of the quality." In addition, in the
      quantitative evaluation, there was a difference in the evaluation of the item for
      which the evaluator's judgment was necessary. Instructors' evaluations were more
      severer than students'. In the "overall evaluation," there was no significant
      relation between the quantitative evaluation score and the score of the overall
      impression. However, there was a significant relationship with the qualitative
      evaluation. From these results, for assignment making, it is necessary for
      examinees to finish the work within the time limit, and that the evaluation not
      affect the performance time. Additionally, it is necessary to standardize the
      evaluation to reduce differences among evaluators, who should be trained.
      Moreover, it was suggested that the selection of an appropriate evaluation system
      for each evaluation item is important in OSCE stations.

PMID- 16462098
TI  - Preparation and evaluation of solid dispersion of meloxicam with skimmed milk.
AB  - Meloxicam (MLX), a non-steroidal anti-inflammatory drug (NSAID) and a selective
      COX-2 inhibitor is a water insoluble drug (about 12 microg/ml). In order to
      improve the aqueous solubility of the drug and its dissolution rate, physical
      mixture and solid dispersions with skimmed milk were prepared and investigated.
      Enhancement of aqueous solubility of MLX was observed with solid dispersion of
      the drug with skimmed milk due to amino acids and surface active agents content
      in the milk, which can be used for the treatment of gastric disturbance. Rotary
      vacuum evaporation technique was used to prepare solid dispersion. Results showed
      that the solubility of solid dispersion of the drug was almost three times
      greater than the pure drug. Similarly, the solid dispersion of the drug indicated
      a significant improvement in the dissolution of the drug as compared to the
      physical mixture and the pure drug. Differential scanning calorimetry, X-ray
      diffraction and scanning electron microscopic analysis revealed the formation of
      solid dispersion of the drug with skimmed milk.

PMID- 16462099
TI  - [Reaction of pyridinium and quinolinium salts having the leaving group at the 2-
      or 4-position with active methylene compounds].
AB  - The reactions of 2- or 4-cyanopyridinium salts with active methylene compounds
      such as dimethyl malonate, malononitrile, and cyclohexane-1,3-dione affording 2-
      or 4-(substituted methylene) pyridines are described. Similar reactions of 4
      cyano-2-methylthiopyridinium and 4-cyano-2-methylthioquinolinium salts, both of
      which have two leaving groups, were readily prepared from 4-cyano-1-methyl-2(1H)
      pyridone and 4-cyano-1-methyl-2(1H)-quinolone via 4-cyano-1-methyl-2(1H)
      thiopyridone and 4-cyano-1-methyl-2(1H)-thioquinolone in two steps, proceeding at
      the 2- and/or 4-positions on the pyridine or quinoline rings.

PMID- 16462100
TI  - [Reaction of pyridinium salts with active methylene compounds].
AB  - The carbon-carbon bond-forming reactions of 1-methyl-2-methylthiophenylpyridinium
      iodides with active methylene compounds (such as dimethyl malonate,
      malononitrile) using NaH as a base gave the 2-substituted methylene-1,2
      dihydropyridine derivatives.

PMID- 16462101
TI  - Role of the opioidergic system and nitric oxide in the analgesic effect of
      venlafaxine.
AB  - The noradrenalin and serotonin re-uptake inhibitor venlafaxine has an analgesic
      effect that is independent of its antidepressant activity; however, the mechanism
      of this effect remains to be elucidated. This study was performed to investigate
      the possible roles of the opioidergic system and nitric oxide (NO) pathway in the
      analgesic effect of venlafaxine. Eighty Wistar rats of both sexes were allocated
      to 10 groups. The hot plate test was used to assess the antinociceptive/analgesic
      effect. The temperature of the hot plate was adjusted to 52.5+/-1 degrees C, the
      cut-off period was set to be 50 sec; licking of the hind paw was used as a sign
      of pain perception. Venlafaxine alone (25 mg/kg) showed marked analgesic activity
      (p<0.05). N-omega-nitro-L-arginine (L-NOARG) alone (20 mg/kg) and naloxone alone
      (2 mg/kg and 4 mg/kg) showed no analgesic activity (p>0.05). Coadministration of
      low-dose naloxone (2 mg/kg) and both doses of L-NOARG (20 and 40 mg/kg) with
      venlafaxine (25 mg/kg) did not modify the analgesic effect but high-dose naloxone
      (4 mg/kg) decreased it significantly (p<0.05). In conclusion, these results
      suggest that the opioidergic system but not the NO pathway has a role in the
      analgesic effect of venlafaxine.

PMID- 16462102
TI  - [Comparison of viewpoints and awareness between patients with and without a
      "family pharmacy"].
AB  - To evaluate differences in viewpoints and awareness between patients with and
      without a "family pharmacy", we performed a questionnaire survey. The
      questionnaire consisted of 21 questions including "I often read books and
      journals about health." and "Patients have the right of being informed of the
      medical treatment they receive". The degree of applicability was selected among 6
      grades ("definitely inapplicable"--"definitely applicable"). The subjects were
      classified into 3 groups "without a family pharmacy", "with a regular pharmacy
      for each hospital/clinic" and "with a family pharmacy", and factor analysis was
      performed. As a result, 5 factors were extracted in each group. However, the
      order of the 2nd-4th factors differed among the 3 groups. Paying attention to
      these differences, we found that patients "with a family pharmacy" have resolved
      doubts about or dissatisfaction with medical care to some extent.

PMID- 16462103
TI  - Phylogeny of Japanese stag beetles (Coleoptera: Lucanidae) inferred from 16S
      mtrRNA gene sequences, with reference to the evolution of sexual dimorphism of
      mandibles.
AB  - As a first step in reconstructing the phylogeny of world stag beetles
      (Coleoptera: Lucanidae), phylogenetic relationships among the major members of
      Japanese stag beetles were explored by analyzing a sequence of 1030 nucleotides
      from the mitochondrial 16S ribosomal RNA (16S rRNA) gene. A total of 20 species
      and three additional subspecies representing 13 genera were examined to provide
      basic information on the phylogeny of world Lucanidae. The resultant phylogenetic
      tree indicates that the family Lucanidae is monophyletic, and contains two major
      lineages: one consists of the genera Platycerus, Aesalus, Ceruchus, and Nicagus,
      and the other includes Dorcus, Rhaetulus, Prosopocoilus, Aegus, Neolucanus,
      Prismognathus, Lucanus, Figulus, and Nigidius. Generic members of the latter
      lineage are further divided into the following four sublineages: i) Figulus and
      Nigidius; ii) Prismognathus and Lucanus; iii) Aegus and Neolucanus; and iv)
      Dorcus, Rhaetulus, and Prosopocoilus. These molecular phylogenetic relationships
      are used as a basis for a preliminary exploration of the evolution of sexual
      dimorphism in the shape of the mandible. The results of this investigation
      suggest that strong sexual dimorphism with well-developed mandibles in males
      evolved independently at least twice, once in the genus Aegus and once in the
      ancestor of the Lucanus-Prismognathus and Dorcus-Rhaetulus-Prosopocoilus clades.
      Alternatively, it is possible that sexual dimorphism of mandibles has undergone
      secondary loss in the genera Figulus and Nigidius.

PMID- 16462104
TI  - New species of Gieysztoria (Platyhelminthes, Rhabdocoela) from Peruvian Amazon
      floodplain with description of their stylet ultrastructure.
AB  - The free-living Platyhelminthes of the Amazon basin are poorly known. Presently
      only four turbellarian species have been mentioned from the Amazon river, a fact
      that confirms the lack of information on this kind of faunas in this huge basin.
      Three new species of Gieysztoria from Amazonian floodplain in Peru are described
      herein: G. chiqchi n. sp., G. kasasapa n. sp. and G. sasa n. sp. The samples were
      taken in the Pacaya-Samiria National Reserve (Peru) during September 2002.
      Besides the usual description of the stylet based on whole mounted specimens, we
      provide a complementary description using SEM, which allowed differentiation of
      the new species within the currently yet imperfect picture of the Amazonian
      turbellarian fauna. Although further research is desired, current findings are
      suggestive of high diversity of free-living Turbellaria in the surveyed region.

PMID- 16462105
TI  - Seasonal variation in the expression of five subtypes of gonadotropin-releasing
      hormone receptor genes in the brain of masu salmon from immaturity to spawning.
AB  - Seasonal variation in the expression of five subtypes of gonadotropin-releasing
      hormone receptor (GnRH-R) genes, designated as msGnRH-R1, -R2, -R3, -R4, and -R5,
      was examined in the brain of masu salmon (Oncorhynchus masou). In addition,
      responses of these genes to GnRH were examined in a GnRH analog (GnRHa)
      implantation experiment. Brain samples were collected one week after the
      implantation every month from immaturity through spawning. The absolute amount of
      GnRH-R mRNA in single forebrains was determined by real-time PCR assays. Among
      the five genes, R4 and R5 were dominantly expressed in both sexes. R1, R4, and R5
      mRNAs showed similar changes throughout the experimental period in both sexes.
      Levels tended to be high in winter and low in the pre-spawning season, followed
      by elevations in the spawning period. The mRNA levels had weak to moderate
      negative correlations with the plasma level of estradiol-17beta (E2) in females.
      The effects of GnRHa on msGnRH-R mRNAs were not apparent for all the subtypes.
      These results indicate that the msGnRH-R1, -R4, and -R5 genes are synchronously
      expressed during sexual maturation. There was a trend toward decreased levels of
      their expression prior to the spawning period and then increased levels at
      spawning, possibly causing GnRH target neurons to sensitize to a GnRH stimulus.
      Furthermore, E2 may be involved in msGnRH-R gene expression in the brain of
      female masu salmon during sexual maturation.

PMID- 16462106
TI  - Regulation of FoxO1 transcription factor by nitric oxide and cyclic GMP in
      cultured rat granulosa cells.
AB  - FoxO1 is a transcription factor implicated in a multitude of physiological
      processes including cell cycle progression, apoptosis and insulin signaling.
      Recent findings indicate that FoxO1 is a key regulator during the proliferation
      and maturation of granulosa cells. Over the past several years, it has become
      evident that nitric oxide (NO) and cGMP modulate ovarian function. There has been
      no information, however, about whether NO-cGMP affects FoxO1 expression or about
      the relationship between NO-cGMP and FoxO1. In the present study, we used
      immunoblot analysis to determine whether NO and cGMP affect FoxO1 expression in
      cultured granulosa cells. Our results clearly showed that FSH suppressed FoxO1
      expression in a time-dependent manner, and that NO-cGMP stimulated FoxO1
      expression in cultured granulosa cells. In addition, this stimulatory effects of
      NO and cGMP can be blocked by FSH in cultured granulosa cells. These findings
      demonstrate that NO and cGMP influence FoxO1 expression possibly through
      antagonizing the action of FSH in cultured granulosa cells. Results of both
      immunoblot analysis and immunohistochemistry also show that estradiol
      implantation do not affect the expression of FoxO1 in rat granulosa cells as
      gonadotrophins do, indicating that mechanism of estradiol on granulosa cells is
      different from gonadotrophins. Together, our experiments suggest that expression
      of FoxO1 in rat granulosa cells can be regulated by gonadotrophins and the
      NO/cGMP signaling pathway.

PMID- 16462107
TI  - Two new records of Oribatula (Zygoribatula) species (Acari: Oribatida) from
      Turkey, with redescriptions.
AB  - The oribatid mite fauna of Turkey is still relatively poorly known. The present
      paper adds two species of oribatid mites to the known Turkish fauna viz.,
      Oribatula (Zygoribatula) debilitranslamellata (Kulijev, 1962) and O. (Z.) exilis
      (Nicolet, 1855). Both species are characterised by large, prominent lamellar
      cusps, with the lamellar setae inserted apically on the cusps, and by the
      presence of distinct translamellae. They can be distinguished, however, by the
      smaller lamellae, absence of cuspidal teeth, narrowly fusiform sensilli and, 13
      pairs of thin, smooth, apically almost flagellate notogastral setae, in O. (Z.)
      debilitranslamellata, and by the wider lamellae, presence of cuspidal teeth,
      widely fusiform sensilli, and 14 pairs of thin, smooth notogastral setae, with
      seta c (1) slightly thicker and minutely barbed in O. (Z.) exilis. The following
      species have been previously reported from Turkey: O. (Z.) cognata (Oudemans,
      1902), O. (Z.) undulata (Berlese, 1917), O. (Z.) terricola Van der Hammen, 1952,
      and O. (Z.) lanceolata Grobler, Bayram & Cobanoglu, 2004.

PMID- 16462108
TI  - Potamothrix scleropenis sp. nov. (Oligochaeta: Tubificidae) from Fuxian Lake, the
      deepest lake in southwest China.
AB  - Potamothrix scleropenis sp. nov. (Tubificidae: Tubificinae) is described from the
      profundal zone (74 m) of Fuxian Lake, the deepest lake (up to 155 m) on the
      Yunnan-Guizhou Plateau in China. The new species is assigned to Potamothrix
      because of its short vasa deferentia and its tubular atria without ejaculatory
      ducts and prostate glands. It differs from congeners by its cuticularized penis
      sheaths; bifurcated, strongly curved spermathecal chaetae; bifurcated lower
      prongs of bifids; and feathered hairs. P. scleropenis appears closely related to
      P. cekanovskajae Finogenova, 1972 and P. tudoranceai Sporka, 1994, since all the
      three species have homogeneous atria without prostate glands.

PMID- 16462109
TI  - Functional and morphological changes in the hypothalamus-pituitary posterior lobe
      system after hypophysectomy in the dog.
AB  - Acute diabetes insipidus-like symptoms have been reported as a complication after
      hypophysectomy in dogs. These symptoms are believed to be the consequence of
      deficiency of arginine vasopressin (AVP) secretion. The symptoms spontaneously
      resolve within 2 weeks, but the mechanism is unclear. In the present study, AVP
      secretion related to increases in Na+ concentration and serum osmotic pressure
      was measured, and immunohistochemical analysis in the paraventricular and
      supraoptic nuclei was performed after hypophysectomy in normal dog. In the
      hypertonic saline test, the plasma AVP concentration slightly increased in
      hypophysectomized dogs, although the increase was markedly smaller than that in
      normal dogs. An immunohistochemical study of the hypothalamus nucleus revealed
      that, AVP-positive cells tended to decrease after hypophysectomy. It suggests
      that excision of the posterior lobe by surgery injured the axon of magnocellular
      neuron in the hypothalamus. A decrease in the function and the number of AVP
      producing and -secreting magnocellular neurons after hypophysectomy, suggests
      that the clinical improvement of postoperative diabetes insipidus-like symptoms
      may not be related to the recovery of AVP secretion.

PMID- 16462110
TI  - Expression of parathyroid hormone-related protein (PTHrP) mRNA in mammary gland
      of periparturient cows.
AB  - The expression of parathyroid hormone-related protein (PTHrP) mRNA was examined
      in mammary gland with or without lactation, and during periparturient period in a
      Holstein cow and a Jersey cow. In the lactating mammary gland, PTHrP was detected
      in alveolar epithelial cells and the lumen by immunohistochemical analysis. The
      relative expression levels of PTHrP mRNA in mammary gland from lactating cows
      were significantly higher than those from non-lactating cows (P<0.05). During
      periparturient period, relative PTHrP mRNA level was remarkably low before the
      parturition in a Jersey and a Holstein cow, however, both levels were gradually
      increased and reached a peak level at 5-6 weeks after the parturition. In
      addition, the peak level in a Jersey cow was approximately 3-fold higher than
      that in a Holstein cow. From these results, PTHrP was synthesized and secreted in
      alveolar epithelial cells in mammary gland and increased subsequently with the
      lactation, suggesting a possible mechanism for the regulation of local calcium
      homeostasis.

PMID- 16462111
TI  - Magnetic resonance imaging of alveolar echinococcosis experimentally induced in
      the rat lung.
AB  - Pulmonary alveolar echinococcosis (AE) caused by the metacestode of Echinococcus
      multilocularis is a lethal zoonosis and is a lesion secondarily induced by
      hematogenous dissemination from hepatic AE lesions. In the present study, a
      hematogenous pulmonary AE model was experimentally induced in rats by the
      injection of echinococcal larval tissue homogenate to the tail vein, and then the
      pathological and diagnostic aspects of pulmonary AE were examined by magnetic
      resonance imaging (MRI). Histological primary, mature and degenerated AE lesions
      were observed 5, 18 and 50 weeks after injection, respectively. These lesions
      were discriminated as signal-void, hypointense and hyperintense regions in T1
      weighted MRI (T1WI), respectively. The change in signal intensity in T1WI might
      reflect the content of proteinaceous fluid as a result of AE cyst degeneration.
      Western blot analysis of sera with antibodies of two epitopes (Em18 and Em16) of
      E. multilocularis provided evidence for AE infection in the early stage. T1WI in
      combination with Western blot analysis could possibility become definitive and
      early signs of hematogenous pulmonary AE infection.

PMID- 16462112
TI  - The prevalence of a group 2 coronavirus in dogs in Japan.
AB  - Canine coronavirus (CCoV) has been reported to cause acute diarrhea mainly in
      young pups. CCoV and feline coronavirus are classified as group 1 coronaviruses.
      However, it has recently been reported in the United Kingdom that the group 2
      coronavirus gene, which is more closely related to the bovine coronavirus (BCoV)
      and human coronavirus strain OC43, has been detected in respiratory tract tissue
      samples from dogs with respiratory disease. In this study, we examined the
      prevalence of antibodies to group 2 coronaviruses in domestic dogs and cats in
      Japan by a neutralization test using BCoV. All 104 feline serum samples were
      negative (<1:5) for anti-BCoV antibodies. In contrast, of the 898 canine serum
      samples, 160 (17.8%) were positive for anti-BCoV antibodies, and the antibody
      titers ranged from 1:5 to more than 1:640, with 1:160 being the most frequent. No
      correlation was found between the titers of the anti-BCoV and anti-CCoV
      antibodies in the 198 serum samples of dogs with a known history of CCoV
      vaccination. We amplified, by RT-PCR, group 2 coronavirus-specific
      hemagglutination/esterase genes in the oral swabs of a total of 10 young pups
      presenting with or having recovered from respiratory signs, or having anti-BCoV
      antibodies, with the result that 2 pups were positive for the
      hemagglutination/esterase genes. These results strongly suggest that an unknown
      group 2 coronavirus as well as the known enteritis-causing CCoV (group 1
      coronavirus) is prevalent among domestic dogs in Japan.

PMID- 16462113
TI  - Sequence variation of bovine prion protein gene in Japanese cattle (Holstein and
      Japanese Black).
AB  - To assess relationships between nucleotide polymorphisms of the prion protein
      (PRNP) gene and susceptibility to bovine spongiform encephalopathy (BSE), we
      investigated polymorphisms in the open reading frame (ORF) and 2 upper regions of
      the PRNP gene from 2 Japanese cattle breeds: 863 healthy Holstein cattle, 6 BSE
      affected Holstein cattle, and 186 healthy Japanese Black (JB) cattle. In the ORF,
      we found single-nucleotide polymorphisms (SNPs) at nucleotide positions 234 and
      576 and found 5 or 6 copies of the octapeptide repeat, but we did not find any
      amino acid substitutions. In the upper region, we examined 2 sites of
      insertion/deletion (indel) polymorphisms: a 23-bp indel in the upper region of
      exon 1, and a 12-bp indel in the putative promoter region of intron 1. A previous
      report suggests that the 23-bp indel polymorphism is associated with
      susceptibility to BSE, but we did not find a difference in allele frequency
      between healthy and BSE-affected Holstein cattle. There were differences in
      allele frequency between healthy Holstein and JB cattle at the 23- and 12-bp
      indels and at the SNPs at nucleotide positions 234 and 576, but there was no
      difference in allele frequency of the octapeptide repeat. We identified a unique
      PRNP gene lacking a 288-bp segment (96 amino acids) in DNA samples stocked in our
      laboratory, but this deletion was not found in any of the 1049 cattle examined in
      the present study. The present results provide data about variations and
      distribution of the bovine PRNP gene.

PMID- 16462114
TI  - Improvement of a rapid diagnosis kit to detect either influenza A or B virus
      infections.
AB  - To improve the sensitivity of a kit, ESPLINE INFLUENZA A&B for rapid diagnosis of
      influenza by detecting influenza A or B virus specific nucleoproteins (NP), the
      ESPLINE INFLUENZA A&B-N was developed by using newly established monoclonal
      antibodies (MAbs) to the respective NP molecule. MAbs FVA2-11 and FrB1-03
      recognize the epitope on the amino acid region 59-130aa of the NP molecule of
      influenza A virus, and that on the region 72-191aa of the NP of influenza B
      virus, respectively. The new kit detected influenza A and B virus antigens with a
      detection limit of 10(2.0)-10 (2.7) pfu/test, which is 4-1000 times higher than
      that of the original kit. Importantly, this kit detected each of influenza A
      viruses of the known hemagglutinin (HA) subtypes (H1-H15) including the H5N1
      viruses recently isolated from human and avian sources in Asia. The kit also
      detected all of the 15 representative influenza B virus strains tested. The
      ESPLINE INFLUENZA A&B-N is thus a rapid and highly sensitive and specific kit for
      the diagnosis of either influenza A or B virus infections.

PMID- 16462115
TI  - Detection of in vivo DNA damage induced by ethanol in multiple organs of pregnant
      mice using the alkaline single cell gel electrophoresis (Comet) assay.
AB  - Ethanol is principal ingredient of alcohol beverage, but considered as human
      carcinogen, and has neurotoxicity. Alcohol consumption during pregnancy often
      causes fetal alcohol syndrome. The DNA damage is one of the important factors in
      carcinogenicity or teratogenicity. To detect the DNA damage induced by ethanol,
      we used an in vivo alkaline single cell gel electrophoresis (Comet) assay in
      pregnant mice organs and embryos. Pregnant ICR mice on Day 7 of gestation were
      treated with 2, 4 or 8 g/kg ethanol, and maternal organs/tissues and embryos were
      subjected to the Comet assay at 4, 8, 12 and 24 hr after ethanol treatment. Four
      and 8 g/kg ethanol induced DNA damage in brain, lung and embryos at 4 or 8 hr
      after the treatment. Two g/kg ethanol did not cause any DNA damage, and 8 g/kg
      ethanol only increased the duration of DNA damage without distinct increase in
      the degree of the damage. No significant DNA damage was observed in the liver. To
      detect the effect of acetaldehyde, disulfiram, acetaldehyde dehydrogenase
      inhibitor, was administered before 4 g/kg ethanol treatment. No significant
      increase of DNA damage was observed in the disulfiram pre-treated group. These
      data indicate that ethanol induces DNA damage, which might be related to ethanol
      toxicity. Since pre-treatment of disulfiram did not increase DNA damage, DNA
      damage observed in this study might not be the effect of acetaldehyde.

PMID- 16462116
TI  - The effect of intermittent administration of sustained release isosorbide
      dinitrate (sr-ISDN) in rats with volume overload heart.
AB  - Recently, it has been reported that intermittent administration of nitrate, with
      a nitrate-free interval of 10 to 12 hr eliminated expression of tolerance, and
      maintained its hypotensive effect. In the present study, we evaluated whether
      nitrate tolerance developed or not with an intermittent administration of sr-ISDN
      (5 mg/kg/ once a day) in Wistar rats. The effect of this administration protocol
      for sr-ISDN on the volume overload heart model, aortovenous fistula, was also
      examined. Furthermore, blood pressure was monitored by radio telemetry during sr
      ISDN (5 mg/kg/once a day) administration. Nitrate tolerance did not develop, and
      eccentric hypertrophy due to volume overload was moderated by sr-ISDN
      administration. Sr-ISDN administration maintained blood pressure lower level than
      the placebo group. In conclusion, prolonged intermittent administration of sr
      ISDN maintained its hypotensive effect during the entire experiment period,
      without developing tolerance, and moderated efferent hypertrophy with attenuated
      volume overload.

PMID- 16462117
TI  - Expression of preproendothelin-2 splice variant in cat.
AB  - Previous studies on human uterine and placental tissues have found variants,
      derived from alternatively spliced mRNAs, of preproendothelin-2 (PPET2) that lack
      a post-translational proteolytic site essential for normal processing. Here we
      report a splice variant of cat PPET2 mRNA expressed in the stomach. After cloning
      the full-length cDNA of cat PPET2, organ distribution analysis of the transcript
      by reverse transcriptase-polymerase chain reaction (RT-PCR) was performed. In
      addition to the fragment with a size predicted based on the cDNA sequence
      obtained by cloning, an additional PCR fragment of smaller size was detected in
      stomach tissue. Subsequent cloning and sequence analysis of the smaller PCR
      product demonstrated that it derives from a splice variant with full-length
      deletion of a region corresponding to exon 4 of the PPET2 gene.

PMID- 16462118
TI  - A new diagnostic indicator using concanavalin a low-affinity lactoferrin levels
      in mammary gland secretion in mastitic drying cows.
AB  - We examined the effective diagnostic indicator using the concanavalin A (Con A)
      low-affinity lactoferrin (Lf) to mastitic drying cows. The concentrations of both
      Lf and Con A low-affinity Lf in mammary gland secretions (MGSs) were lower than
      normal MGSs at the early and middle dry periods and colostrums. On the other
      hand, the levels of Con A low-affinity Lf in MGSs increased following the
      appearance of mastitis symptoms, and decreased when the mastitic symptoms were
      cured. Moreover, IgG1 concentrations of colostrums decrease on the quarters where
      a high level of Con A low-affinity Lf was determined after the onset of dry
      period. These results suggest that this method could be used as a useful
      indicator to mastitic drying cows.

PMID- 16462119
TI  - Erythropoietin-producing cells in the liver of ICR-derived glomerulonephritis
      (ICGN) mice.
AB  - The ICR-derived glomerulonephritis (ICGN) mouse is an appropriate model for
      anemia associated with chronic renal disorder (CRD). Insufficient renal
      production of erythropoietin (EPO) induces the anemia associated with CRD. EPO
      mRNA is expressed in both kidneys and liver of progressing-stage ICGN mice.
      Hypoxic stimulation induced the EPO mRNA expression in the liver as well as in
      the kidneys of ICGN mice. The localization of EPO-producing cells in the liver
      remains controversial. Present study using an amplified in situ hybridization
      technique identified that nonparenchymal cells were the source of hepatic EPO
      production in ICGN mice under both normoxia and hypoxia.

PMID- 16462120
TI  - Survey of gastrointestinal parasitic infections in quarantined dogs in Taiwan.
AB  - Intestinal helminth and protozoan infection in the quarantined dogs in Taiwan
      were examined using fecal examination between January to December, 2004. Of the
      376 dogs imported from 11 countries, 63 (16.8%) were found to be infected with at
      least one species of intestinal parasite. The parasites detected were oocysts of
      Isospora canis and eggs of Toxocara canis, Trichuris vulpis and hookworms. Of the
      63 infected dogs, 11 were found to have a mixed infection of two different
      species of parasites. This paper illustrates that parasites are transmitted from
      one country to another through the transport of animals. Moreover, there is also
      a possibility of parasitic infection among quarantined dogs as well as the
      zoonotic potential for quarantine officers during the quarantine period.

PMID- 16462121
TI  - An immunohistochemical study of protein kinase C in the bovine retina.
AB  - The expression of protein kinase C (PKC) was studied in the bovine retina by
      immunohistochemical analysis. Western blot analysis showed that PKC isoforms,
      including alpha, betaI, delta and theta, were detected in the bovine retina. By
      immunohistochemistry, both PKC alpha and betaI were expressed in all retinal
      layers, with an intense localization of both PKC alpha and betaI detected in
      bipolar cells in the inner nuclear cell layer and in some glial cells in ganglion
      cell layers. The immunoreactivity of both PKC delta and theta was quite weak in
      the retinal layers, compared with that of PKC alpha and betaI. These findings
      suggest that both conventional and novel PKCs are differentially expressed in the
      bovine retina.

PMID- 16462122
TI  - Effect of dietary administration of bananas on immunocytes in F1 hybrid calves.
AB  - The effect of dietary administration of bananas on immunocytes in calves was
      investigated. Twenty Fl hybrid calves were used in this study (treated group
      n=10, control group n=10). Banana (2 g/kg BW) was administered to the calves for
      5 days. Leukocyte subsets were examined on days 0, 5, 10, and 15. The numbers
      CD3+, (CD3+)CD45R-, and (CD3+)TcR+ cells significantly increased between day 0
      and day 5 in the treated group (P<0.01), and were significantly higher on day 5
      in the treated group relative to the control group (P<0.05). These data showed
      that feeding banana to calves increased T-lymphocytes, suggesting it might be
      possible to enhance protective functions against infections.

PMID- 16462123
TI  - Age-associated changes of flash visual evoked potentials in dogs.
AB  - Age-associated changes of visual evoked potentials by flash stimulation (flash
      VEP) were evaluated in 53 beagle dogs aged from 1- to 15-year-old. Among the
      components of flash VEP consisted of 3 positive (P1, P2 and P3) and 2 negative
      (N1 and N2) peaks by 150 msec, the latency of P2 and the later peaks (N2 and P3)
      were significantly delayed with aging. Both amplitudes of the P2-N2 and N2-P3
      also showed a significant correlation with aging. The flash VEP is considered to
      be an available and useful technique to evaluate not only for visual pathway, but
      also some disturbance of neurological functions, like as those reported in
      demented human.

PMID- 16462124
TI  - Sporadic cases and an outbreak of leptospirosis probably associated with
      recreational activities in rivers in the northern part of Okinawa Main Island.
AB  - In the summer of 2003, sporadic cases and an outbreak of human leptospirosis
      probably related to recreation in rivers occurred in the northern part of Okinawa
      Main Island. Sixteen of 22 suspected cases were definitely diagnosed as
      leptospirosis by serological test or isolation. The infective leptospiral serovar
      in 14 cases was presumed to be Hebdomadis. Transmission was thought to occur by
      exposure to river water that was contaminated by the urine of infected animals.
      The findings indicate that recreation in rivers in this area is a significant
      risk factor for infection with leptospires.

PMID- 16462125
TI  - Cell surface expression of a chimeric protein containing mouse immunoglobulin G1
      Fc domain and its immunological property.
AB  - Recently we reported that a chimeric molecule containing mouse transferrin
      receptor and immunoglobulin G1 (IgG1) Fc, mTR-Fc, induced higher immune responses
      and can be used as a vaccine adjuvant. In this study, the immunological property
      of the molecule was investigated. Although, the mTR-Fc did not activate
      complement classical pathway, it was recognized by activated macrophage as like
      intact IgG Fc, which is recognized by macrophage via Fcgamma receptor. In
      addition, we found that splenocyte simultaneously exposed to lipopolysaccaride
      (LPS) and mTR-Fc produced higher amount of interleukin-10, comparing to that
      exposed to only LPS. These results suggest that the mTR-Fc molecules conserved
      the IgG Fc property to biasing immune responses via modulation of cytokine
      production by antigen presenting cell.

PMID- 16462126
TI  - Serotypes and mating types of clinical isolates from feline cryptococcosis in
      Japan.
AB  - Most isolates of Cryptococcus neoformans (teleomorph: Filobasidiella neoformans)
      from human patients and from environmental materials in Japan have been
      identified as serotype A mating type a by the seroagglutination test and mating
      experiments. A PCR method using the mating type alpha allele-specific primer of
      the STE12 gene and the serotype- and mating type-specific primers of the STE20
      gene for identification of C. neoformans has been developed. Using the PCR
      method, conserved strains and clinical isolates from feline cryptococcosis were
      examined for serotype and the mating type. The results showed that all clinical
      isolates examined were identified as serotype A, MATalpha, indicating that feline
      cryptococcsis cases in Japan are caused by C. neoformans serotype A, MATalpha, as
      is the case in humans.

PMID- 16462127
TI  - Systemic treatment of sterile panniculitis with tacrolimus and prednisolone in
      dogs.
AB  - This report deals with three additional canine cases of sterile panniculitis
      treated by oral administration of tacrolimus and prednisolone. The oral
      tacrolimus treatment was proved to be an affordable medical protocol for canine
      sterile panniculitis with good efficacy and without adverse effects.

PMID- 16462128
TI  - A cat with acute myeloblastic leukemia without maturation (M1) treated with
      combination chemotherapy.
AB  - A 2-year-old domestic shorthair cat was presented to us with decreased activity
      and anorexia. Hematologic findings revealed a mild non-regenerative anemia,
      thrombocytopenia, and leukocytosis with an increase in blast cells. Bone marrow
      aspirates also revealed a marked increase of blasts. The blastic cells were shown
      to be positive for peroxidase. Acute myeloblastic leukemia without maturation
      (M1) was diagnosed according to the FAB classification. Chemotherapy was
      initiated with cyclophosphamide, vincristine, prednisolone, and cytosine
      arabinoside. The cat responded partially. In total, the cats were given 7 blood
      transfusions. The cat died 14 weeks after first being presented to us.

PMID- 16462129
TI  - First Thelazia callipaeda infestation report in a dog in Taiwan.
AB  - An ocular Thelazia callipaeda infestation was found in a male domestic dog in
      Taiwan during regular examination. This is the first report of the parasite from
      pet animal in Taiwan. The infested dog showed normal bodily condition but slight
      conjunctival congestion. This parasite has been reported in humans in southeast
      Asia, China and Korea. In 1998, first human case was reported in the central area
      of Taiwan. The dogs infected with T. callipaeda may have important implication in
      the infestation of this parasite to humans as reservoir hosts.

PMID- 16462130
TI  - Evaluation of esophageal peristalsis in patients with esophageal tumors: initial
      experience with cine MR imaging.
AB  - We evaluated esophageal peristalsis in patients with esophageal tumors by cine MR
      using steady-state free precession (SSFP) sequence and correlated the alteration
      of the esophageal peristalsis with clinical symptoms and tumor stages. Thirteen
      patients with pathologically proven esophageal tumors, including 12 esophageal
      cancers and one submucosal leiomyoma, underwent cine MRI using true fast imaging
      with steady precession (trueFISP) sequence, which is one SSFP sequence, after
      contrast-enhanced MR scanning for clinical purposes. A total of 120 serial images
      were obtained within 60 s through the plane along the long axis of the esophagus
      while patients chewed gum. The serial trueFISP images were evaluated for the
      presence, frequency, speed of progression, and passage of peristalsis through the
      tumor. The data from cine MRI were compared with clinical symptoms and tumor
      stages. Peristalsis was clearly identified in all patients. Seven patients with
      complete interruption of peristalsis had dysphagia; one with partially impaired
      peristalsis could intake solid foods with discomfort; and two with partially
      impaired peristalsis and three with preserved peristalsis remained asymptomatic.
      Patients with complete or partial interruption of peristalsis had Stage T3 or T4
      esophageal cancer. In conclusion, trueFISP cine MR imaging enables direct
      visualization of esophageal peristalsis in relation to esophageal tumors.
      Complete interruption of peristalsis causes dysphagia, whereas partial
      interruption of and preserved peristalsis usually do not cause digestive
      problems. Interruption of peristalsis may indicate impaired muscle function
      caused by invasion of advanced esophageal cancers.

PMID- 16462131
TI  - Temporal relationship between action and visual outcome modulates brain
      activation: an fMRI study.
AB  - Monitoring the visual outcome of our actions is critical to our visuo-motor
      behavior. To investigate the neural basis of monitoring visual change produced by
      self-movement, we examined the temporal relationship between manual depression of
      a button and visual feedback on activation of the brain. Six neurologically
      normal subjects participated in 3 experiments (synchronous, delayed, and visual
      [control]). Magnetic resonance (MR) images of their brains were acquired during
      the experiments using a scanner operating at 3T. In the synchronous experiment,
      subjects pressed a button at self-paced intervals and received synchronous visual
      stimuli in response. In the delayed experiment, visual stimuli were presented
      with a delay after subjects pressed a button at self-paced intervals. In the
      control experiment (visual experiment), subjects did not press the button, but
      viewed visual stimuli generated by a computer at random intervals. In the
      synchronous experiment, activation in the cerebellum and right parietal lobe was
      stronger than in the delayed experiment, whereas activation in the primary visual
      cortex was weaker than in the delayed and visual experiments. These results
      suggest that visual outcomes produced synchronously with action are processed in
      the cerebellum and the parietal area for the organization of optimal motor
      behavior, rather than in the primary visual area that is known to process the
      visual properties of external objects. The cerebellar signal related to visuo
      motor contingency may modulate the cortical processing of visual input that is
      synchronous with action.

PMID- 16462132
TI  - Proton MR spectroscopy of adult-onset dentatorubral-pallidoluysian atrophy.
AB  - PURPOSE: To quantify impairment of the basal ganglia (globus pallidus and
      thalamus) in adult-onset dentatorubral-pallidoluysian atrophy (DRPLA). METHODS:
      Five patients with genetically definite adult-onset DRPLA (aged 51 to 65 years,
      mean 55.6 years) and 5 age- and sex-matched healthy controls underwent
      conventional magnetic resonance imaging (MRI) and proton magnetic resonance
      spectroscopy (MRS) of the brain in the voxels predominantly containing the globus
      pallidus or the thalamus. RESULTS: Conventional MRI studies showed apparently
      normal intensities in the globus pallidus and thalamus. MRS showed that the
      choline (Cho)/creatine (Cr) ratio for the patients' globus pallidus, the region
      preferentially affected in DRPLA, was significantly higher than that in the
      controls (p<0.05). The N-acetylaspartate (NAA)/Cr ratio for the globus pallidus
      and the Cho/Cr and NAA/Cr ratios for the thalamus, the region relatively spared
      in this disease, did not differ significantly between the patients and controls.
      CONCLUSIONS: MRS may sensitively and specifically detect biochemical alterations
      in susceptible regions of patients with adult-onset DRPLA.

PMID- 16462133
TI  - Intelligent operating theater using intraoperative open-MRI.
AB  - Malignant brain tumors vary among patients and are characterized by their
      irregular shapes and infiltration. Localization of functional areas in the brain
      also differs among patients, and excess removal of tumor near eloquent areas may
      increase the risk of damage of function, such as motor paresis and speech
      disturbance. Recent progress in magnetic resonance (MR) imaging technology has
      enabled acquisition of intraoperative images and totally changed the neurosurgery
      of malignant brain tumors. Before, surgeons could merely speculate about the
      results of surgical manipulation and have no certainty about procedure outcomes
      until postoperative examination. Because intraoperative MR images allow
      visualization of the size of residual tumor(s) and the positional relationship
      between the tumor(s) and eloquent areas, surgeons are now able to achieve safe
      and reliable surgery. As an example, positional error on preoperative MR images
      caused by shifting of the brain (brain shift), a long-standing annoyance for
      surgeons, has been resolved using intraoperative MR images for surgical
      navigation, allowing precise resection. Two types of open-MR imaging scanner, a
      0.2- or 0.3-tesla hamburger-type scanner with a horizontal gap and a 0.12- or 0.5
      tesla double doughnut-type scanner with a vertical gap, are now available in the
      operating theater, and 1.5-tesla bore-type scanners are available. A 3.0-tesla
      bore-type scanner is planned. Intraoperative MR imaging includes diffusion-tensor
      and diffusion-weighted imaging, which allows visualization of nerve fibers in the
      white matter, especially the pyramidal tract. Such images are valuable aids in
      the precise resection of residual lesions of malignant brain tumors near eloquent
      areas without injuring motor function.

PMID- 16462134
TI  - Development of a compact mouse MRI using a yokeless permanent magnet.
AB  - A compact mouse MRI has been developed using a 1.0T yokeless permanent magnet and
      portable MRI console. The entire system was installed in a space measuring 2 m x
      1 m. The imaging region was the cylindrical volume (35 mm diameter, 50 mm length)
      at the center of the magnet and was used for whole-brain or body imaging of mice.
      Whole-brain imaging took less than 90 min for T1- and T2-weighted 3D images with
      2-mm slice thickness and 200-microm in-plane resolution. Body imaging took less
      than 30 min for T1-weighted spin-echo and FLASH 3D images with 0.5- to 1.0-mm
      slice thickness and 250- to 300-microm in-plane resolution. In addition to the
      compactness of the system, the mouse MRI has several advantages over high-field
      superconducting animal MRI systems in its accessibility to the specimen,
      similarity to clinical MRI in image contrast, capacity for biological isolation,
      and maintenance. The results obtained demonstrate the potential of this new
      system for routine imaging in biomedical laboratories.

PMID- 16462135
TI  - Enhancement effects and relaxivities of gadolinium-DTPA at 1.5 versus 3 Tesla: a
      phantom study.
AB  - PURPOSE: To investigate the difference in enhancement effects and relaxivities of
      the gadolinium chelate at 1.5 and 3 Tesla (T) and to elucidate the contribution
      of the high magnetic field to contrast enhancement in spin-echo (SE) and gradient
      echo (GRE) images. METHODS: Phantoms containing water with or without
      gadopentetate dimeglumine (Gd-DTPA) at different concentrations were scanned
      using 1.5T and 3T MRI scanners of the same manufacturer and under the same
      temperature conditions and scanning parameters. Relaxivities of gadolinium, R1
      and R2, were estimated from serial T1 and T2 values of the phantoms using linear
      regression. Contrast enhancement ratios in SE and GRE T1-weighted images were
      compared at 1.5 and 3T. RESULTS: The R1 and R2 of Gd-DTPA at 1.5 and 3T were 4.79
      and 5.14, and 4.50 and 5.09, respectively. Although the relaxivities at 3T were
      slightly lower than those at 1.5T, the contrast enhancement ratio improved in
      both SE and GRE images as a result of T1 prolongation of the water at 3T.
      CONCLUSION: The decrease in relaxivities of the Gd-DTPA at 3T appears to be so
      small that T1 prolongation of the water improves contrast enhancement, suggesting
      a potential clinical advantage in administration of Gd-DTPA at high field
      strength.

PMID- 16462136
TI  - Chlorine in breath condensate--a measure of airway affection in pollinosis?
AB  - BACKGROUND: Infiltration of inflammatory cells in bronchial mucosa and glandular
      hypersecretion are hallmarks of asthma. It has been postulated that exhaled
      breath condensate (EBC) mirrors events in epithelial lining fluid of airways,
      such as presence of local inflammation as well as glandular hypersecretion. It is
      also well known that eosinophil cationic protein (ECP) and cysteinyl-leukotrienes
      (cys-LT) are released by circulating inflammatory cells when triggered by antigen
      stimulation in asthma patients. OBJECTIVES: The aim of this study was to evaluate
      whether chlorine and/or cys-LT in EBC would reflect changes of exposure of
      airborne pollen in patients with asthma. METHODS: EBC and serum were collected
      from 23 patients with allergic asthma during a pollen season and repeated 5
      months later during a period with no aeroallergens. Chlorine was measured by
      means of a sensitive coulometric technique and cys-LT by an EIA technique. Serum
      ECP was measured and lung function tests were performed and symptoms noted during
      both occasions. RESULTS: Significantly higher concentrations of chlorine in EBC
      (p = 0.007) and ECP in serum (p = 0.003) were found during the pollen season
      compared to post-season. Chlorine levels tended to be higher in patients who
      reported of chest symptoms compared to those who denied symptoms during the
      pollen season (p = 0.06). Areas under the receiver-operated characteristic curves
      (AUC(ROC)) were compared and similar discriminative power to identify
      exacerbations of asthma was recorded by chlorine in EBC (range 0.67-0.78) and ECP
      in serum (range 0.64-0.78). CONCLUSION: It is concluded that chlorine in EBC and
      ECP in serum decreased significantly post-season, and this is suggested to mirror
      the decrement in airborne antigen. It is furthermore proposed that chlorine in
      EBC and ECP in serum tend to have a similar capacity to identify seasonal
      variations in airborne pollen in patients with asthma.

PMID- 16462137
TI  - The effects of weather on the incidence of sudden sensorineural hearing loss: a 5
      year population-based study.
AB  - OBJECTIVE: This study utilizes 5-year population data to examine the association
      between weather conditions and the incidence of sudden sensorineural hearing loss
      (SSNHL) in Taiwan with a specific focus on ambient temperature, relative
      humidity, atmospheric pressure, rainfall and total hours of sunshine. METHOD: The
      data, covering the period from 1998 to 2002, is sourced from the Taiwan National
      Health Insurance Research Database (NHIRD), with a total of 8712 first-time
      admissions being identified from the database by a principal diagnosis of
      unspecified sudden hearing loss (ICD-9-CM code 3882). After controlling for time
      trend effects, this study adopted the autoregressive integrated moving average
      regression method as a means of evaluating the effects of climatic and monthly
      factors on SSNHL incidence rates. RESULTS: Although significant associations were
      found between ambient temperature, relative humidity and the SSNHL incidence
      rates for the total population, after adjusting for seasonality, months and
      trends, the significant relationship between SSNHL incidence rates and the
      climatic parameters disappeared. CONCLUSIONS: This study has demonstrated that
      after adjusting for seasonality, months and trends, there is no significant
      relationship between monthly SSNHL incidence rates and weather conditions.
      Therefore, the theory that weather is a triggering factor in SSNHL pathogenesis
      is not supported by this study.

PMID- 16462138
TI  - Improving the management of anemia in hemodialysis patients by implementing the
      continuous quality improvement program.
AB  - BACKGROUND: Anemia is common in hemodialysis patients, and improvement in anemia
      management is possible with the implementation of continuous quality improvement
      (CQI) programs. The aim of this study is to improve anemia management in chronic
      hemodialysis patients using CQI. METHODS: Ninety hemodialysis patients in our
      single center were enrolled in the study. The patients were followed up from
      January 2004 to October 2005. The CQI team-oriented approach was driven by a
      process called the 'FOCUS-PDCA cycle plan' (find, organize, clarify, uncover,
      start, plan, do, check and act). Hemoglobin (Hb), serum ferritin and transferrin
      saturation were monitored periodically. RESULTS: By implementation of the CQI
      program, the proportion of patients with Hb >or=110 g/l increased from 42.2 to
      60.0% (p < 0.05), and the Hb level increased from 101.2 +/- 18.05 to 110.4 +/-
      14.23 g/l (p < 0.0001). The proportion of patients with an adequate iron status
      increased from 28.0 to 53.3% (p < 0.05). CONCLUSION: The CQI program is a useful
      method in the management of anemia in hemodialysis patients.

PMID- 16462139
TI  - Regulation of intracellular calcium levels and urokinase activity in MDA MB 231
      cells by quercetin.
AB  - BACKGROUND: The common plant bioflavonoid, quercetin, is cytotoxic to various
      tumor cell lines, particularly breast cancer, by affecting the protein-kinase-C
      dependent signal pathways and by cell cycle regulation. However, its role in
      breast cancer metastasis has not been studied so far. Increased uPA activity is
      evident in highly metastatic breast cancer, which is calcium dependent. METHODS:
      MDA MB 231 cells were treated with various concentrations of quercetin (15-45
      microg/ml). The cytotoxic effect of quercetin was assessed by MTT assay and DNA
      fragmentation analysis. Intracellular calcium levels were measured using Fura-2,
      a specific Ca2+ fluorescence indicator. Calcium uptake and release in cells
      treated with quercetin were measured using radioactive 45Ca2+. Urokinase enzyme
      activity was assayed by a casein zymogram. RESULTS: Quercetin elicited dose- and
      time-dependent cytotoxicity as evidenced by the MTT assay. The maximum effect was
      observed at 48 h with a quercetin concentration of (45 microg/ml). DNA agarose
      gel electrophoresis showed dose-dependent DNA fragmentation on quercetin
      treatment. Quercetin caused significant depletion of cytosolic calcium levels and
      decreased calcium uptake from the intracellular stores. Casein zymogram showed a
      marked reduction of urokinase activity as evident by clear lysis bands on a dark
      background on treatment with quercetin. CONCLUSION: Quercetin was found to
      exhibit cytotoxicity in the highly invasive breast cancer cell line MDA MB 231 in
      a dose- and time-dependent manner. Quercetin inhibited calcium dependent
      urokinase activity and hence may prove to be an effective antimetastatic agent.

PMID- 16462140
TI  - New aspects of copper and iron metabolism in the myelodysplastic syndromes.
AB  - BACKGROUND: Myelodysplastic syndrome (MDS) is an iron overload condition. Copper
      deficiency itself might induce dysplastic changes and iron overload. The
      relationship between the iron and copper metabolism is analyzed in MDS patients.
      METHODS: Copper, iron and ceruloplasmin levels were established, and transferrin
      saturation determination and HFE mutation analysis were performed in 32 MDS
      patients. RESULTS: Eleven of 32 MDS patients were copper deficient. A decreased
      copper level occurred together with a significantly elevated iron level and
      transferrin saturation and in 45% HFE gene mutation. In the normal copper group,
      twice as many patients had a decreased rather than an elevated iron content and
      carried the wild-type HFE gene rather than the mutant. CONCLUSIONS: Copper
      deficiency is a frequent finding in MDS. It is desirable to include copper level
      determination in the initial workup of MDS.

PMID- 16462141
TI  - Sunflower seed oil-enriched product can inhibit Ehrlich solid tumor growth in
      mice.
AB  - BACKGROUND: Sunflower seed oil (SSO) effect on solid and ascitic forms of Ehrlich
      tumor was evaluated. METHODS: Solid or ascitic Ehrlich tumor-bearing Swiss mice
      were treated daily, by subcutaneous route, with 200 microl of SSO. The solid
      tumor-bearing footpad was measured every 3 days and ascitic tumor-bearing mice
      had their ascites collected and quantified. At the end of the SSO treatment, the
      total cell number in lymphoid organs was quantified. RESULTS: Subcutaneous
      treatment with SSO inhibits the solid tumor growth and increases lymph node cell
      number in animals with solid tumor, but has no effect on animals with ascitic
      tumor. CONCLUSIONS: SSO can delay the solid tumor growth, possibly due to better
      absorption of this treatment by draining lymph nodes.

PMID- 16462143
TI  - Female child sexual abuse within the family in a Hungarian County.
AB  - BACKGROUND: The aim of the study was to analyze the characteristics of
      intrafamiliar female child sexual abuse and to explore common features that may
      be utilized as targets for possible methods of prevention. We also described the
      medical and legal approaches to handling child neglect. METHODS: This was a
      descriptive, cross-sectional study on 52 sexually abused girls under the age of
      18 at the Department of Obstetrics and Gynecology, Medical and Health Science
      Center of Debrecen. We prospectively recorded the data of all cases.
      Intrafamiliar events were defined if the victim and perpetrator belonged to the
      same family. Legal outcomes were also recorded. RESULTS: During the 16-year
      period, 209 cases of sexual abuse were seen in our clinic, 52 of them had been
      involved in child sexual abuse within the family. This accounts for 25% of
      adolescent cases. Eighty-six percent of the victims were pupils, 50% of them were
      between 11 and 14 years of age. The perpetrator was the victim's father in 44%,
      and the stepfather in 40%. There was a slight difference between the type of
      abuse among the pre- and postpubertal group of victims, but statistically it was
      not significant. The abuse occurred on multiple occasions in 52%. The occurrence
      rate of assault was the highest in the summer season (58%), mostly in the
      afternoon (42%) and it took place almost exclusively at home (98%). The mother
      accompanied the victim in 38% of the cases and the police in 40%. Vaginal
      penetration was the type of abuse in 75%, and sexual perversion in 25%. Six
      victims were physically injured, the presence of sperm could be confirmed on
      vulvovaginal smears in 2 cases. One pregnancy conceived. Nine cases were reported
      to the police and as a result of legal proceedings, 5 perpetrators have been
      sentenced. CONCLUSION: The majority of crimes take place within the family and
      are disclosed after multiple episodes. The small proportion of reported sexual
      assaults is the consequence of the lack of harmony between the Hungarian
      conditions of emergency care and the criminal law. Prevention calls for attention
      at all levels of child education, observation at off-school times, early
      involvement of health professionals, applying standardized medical guidelines and
      the modification of jurisdiction.

PMID- 16462142
TI  - Acute alterations in biochemistry, morphology and contractility of rat isolated
      urinary bladder via increased intra-abdominal pressure.
AB  - OBJECTIVE: To determine the acute effects of increased intra-abdominal pressure
      (IAP) on the biochemistry, morphology and contractility of the rat isolated
      urinary bladder using an experimental laparoscopy model. METHODS: We divided 24
      adult female Sprague-Dawley rats into three groups. The control group (group I)
      was not subjected to increased IAP. In groups II and III, IAPs of 10 and 20 mm
      Hg, respectively, were established by carbon dioxide pneumoperitoneum for 60 min.
      Thirty minutes after desufflation, the rat urinary bladder dome was removed for
      in vitro pharmacological investigation, measurement of malondialdehyde (MDA)
      levels and histopathological examination. Statistical comparisons between groups
      were performed. RESULTS: Tissue MDA levels in groups II and III were
      significantly higher than in the control group. In group II, only the lamina
      propria was significantly damaged. However, the epithelium, lamina propria, and
      serosa were significantly damaged in group III. Acetylcholine potentiated
      contractions in both IAP groups. Increased responses to electrical field
      stimulation in the IAP groups were significant only in group II. CONCLUSIONS: In
      this experimental model, 10 and 20 mm Hg of IAP induced by pneumoperitoneum
      increased MDA levels and caused important changes in the morphology and
      contractile response of the urinary bladder.

PMID- 16462144
TI  - Serum IGF-I and IGFBP-3 levels of Turkish children during childhood and
      adolescence: establishment of reference ranges with emphasis on puberty.
AB  - AIMS/METHODS: We established age- and sex-related reference ranges for serum
      insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding
      protein-3 (IGFBP-3) levels in 807 healthy Turkish children (428 boys, 379 girls),
      and constructed a model for calculation of standard deviation scores of IGF-I and
      IGFBP-3 according to age, sex and pubertal stage. RESULTS: Serum IGF-I and IGFBP
      3 concentrations tended to be higher in girls compared to boys of the same ages,
      but the differences were statistically significant only in pubertal ages (9-14
      years) for IGF-I and only in prepubertal ages for IGFBP-3 (6-8 years) (p < 0.05).
      Peak IGF-I concentrations were observed earlier in girls than boys (14 vs. 15
      years, Tanner stage IV vs. V) starting to decline thereafter. IGFBP-3 levels
      peaked at age 13 and at Tanner stage IV in both sexes with a subsequent fall.
      Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal
      stage followed by a rapid increase in IGF-I in the early pubertal stages. A
      relatively steeper increase in IGF-I but not in IGFBP-3 levels was observed at
      age 10-11 years in girls and at 12-13 years in boys which preceded the reported
      age of pubertal growth spurt. At late pubertal stages, both IGF-I and IGFBP-3
      either did not change or decreased by increasing age. Interrelationships between
      growth factors and anthropometric measurements have been described, and the
      physiologic consequences of these have been discussed in detail. CONCLUSIONS:
      Differences in the pattern of IGF-I and IGFBP-3 in the present paper and those
      reported in other studies emphasize the importance of locally established
      reference ranges. Establishment of this reference data and a standard deviation
      score prediction model based on age, sex and puberty will enhance the diagnostic
      power and utility of IGF-I and IGFBP-3 in evaluating growth disorders in our
      population.

PMID- 16462145
TI  - Liquorice in moderate doses does not affect sex steroid hormones of biological
      importance although the effect differs between the genders.
AB  - BACKGROUND/AIM: Liquorice is commonly consumed, at least in the western world,
      and we have earlier shown that even moderate doses of liquorice have significant
      effects on the cortisol metabolism by inhibiting 11beta-hydroxysteroid
      dehydrogenase type 2. The suggestion that liquorice decreases the testosterone
      levels in men makes it vital to study the effect of moderate doses of liquorice
      on sex steroid hormones. METHODS: Fifteen women and 21 men (healthy volunteers
      and subjects with essential hypertension) consumed 100 g of liquorice (150 mg
      glycyrrhetinic acid) daily in a 9-week, open-treatment trial. Blood and 24-hour
      urine samples were collected for hormone analysis before and after 4 weeks of
      liquorice consumption and 4 weeks after cessation of liquorice intake. RESULTS:
      The liquorice induced a moderate decrease in the serum concentrations of
      dehydroepiandrostenedione sulphate in men (p = 0.002). The relative change in
      serum levels of dehydroepiandrosterone sulphate differed between the genders (p =
      0.03). No significant changes were observed in the serum testosterone levels
      after 4 weeks of liquorice consumption, and the urine excretion of androgens
      (etiocholanolone and androstenedione) did not change. CONCLUSIONS: Liquorice in
      moderate doses primarily affects the cortisol metabolism and only marginally the
      androgen hormones. Gender may influence the action of liquorice.

PMID- 16462146
TI  - Global inequalities in paediatric endocrine practice: statement of minimal
      acceptable care. Statement from the international societies for paediatric
      endocrinology.

PMID- 16462148
TI  - Endoscopic surgery with powered instrumentation for isolated sphenoid sinus
      disease.
AB  - OBJECTIVE: Isolated sphenoid sinus disease (ISSD) is a relatively uncommon
      disease. In this study, we investigate the diagnosis and pathology of ISSD and
      compare endoscopic treatment with powered instrumentation with conventional
      surgical instruments for ISSD. METHODS: Ninety-six out of 2,263 patients who
      underwent endoscopic surgery were diagnosed with ISSD by nasal endoscopy and
      computed tomography scan. Ninety-six cases of confirmed ISSD were treated by
      endoscopic sphenoidotomy, of which 44 cases were operated using powered
      instrumentation and 52 using conventional instruments. All patients were followed
      up for a period ranging from 18 to 54 months (mean 26 months) and the surgical
      outcomes were retrospectively reviewed. RESULTS: The pathological findings of
      these patients included sphenoid sinusitis, fungal disease, sphenoid cyst,
      inverted papilloma, malignant tumor, sphenoid polyp, and foreign body. The most
      common initial symptom was headache, followed by visual changes and nasal
      symptoms. After endoscopic surgery, drainage of the sphenoid was accomplished in
      87 of the 96 patients (91%). Of all patients, 9.4% (9/96) had recurrent
      incidence, 22% (21/96) sphenoid ostium synechia, and 51% (49/96) partial middle
      turbinectomy. Comparing the surgical outcomes between two operative approaches,
      recurrent incidence, sphenoid ostium synechia, and partial middle turbinectomy
      were significantly lower in the powered instrumentation group (2, 7, and 14%)
      than in the conventional instrument group (15, 35, and 83%;p < 0.05). No serious
      complication occurred in either group. CONCLUSIONS: Powered instrumentation is
      more effective than conventional instruments in the treatment of ISSD and
      provides a minimally invasive surgical approach to the sphenoid sinus.

PMID- 16462147
TI  - McCune-Albright syndrome in a boy may present with a monolateral macroorchidism
      as an early and isolated clinical manifestation.
AB  - BACKGROUND: Testis enlargement in McCune-Albright syndrome (MAS) is generally
      bilateral and associated with clinical and biochemical manifestations of sexual
      precocity. CASE REPORT: We describe for the first time an unreported clinical
      expression of MAS in a 4.6-year-old boy presenting with monolateral testis
      enlargement and no signs of sexual precocity or other clinical manifestations of
      MAS at the time of presenting with macroorchidism. Both testosterone and LHRH
      stimulated gonadotropin levels were in the prepubertal range. Serum inhibin B was
      increased to a pubertal level indicating Sertoli cell activation. The
      histological and immunocytochemical evaluation of the enlarged testis revealed
      Sertoli cell hyperplasia with no mature Leydig cells. Mutation R201C of GNAS1
      gene, classically responsible for MAS, was identified in DNA samples from the
      right testis biopsy and leukocytes. CONCLUSIONS: (a) MAS should be taken into
      consideration in the clinicopathological approach to a boy with monolateral
      macroorchidism; (b) testicular enlargement may be only the presenting clinical
      manifestation of MAS and is not necessarily linked to manifestations of
      peripheral precocious puberty; (c) testicular autonomous hyperfunction in MAS may
      be restricted to Sertoli cells, as also demonstrated previously by others.

PMID- 16462149
TI  - High prevalence of Streptococcus pneumoniae with mutations in pbp1a, pbp2x, and
      pbp2b genes of penicillin-binding proteins in the nasopharynx in children in
      Japan.
AB  - OBJECTIVE: To evaluate the resistances of Streptococcus pneumoniae to beta
      lactams developed by stepwise alterations in high-molecular-weight penicillin
      binding proteins (PBPs) with a reduced binding affinity of beta-lactams. Among
      the numerous mutations in pbp genes that alter the affinity for beta-lactams, the
      decreased affinity of PBP1A, 2X and 2B is especially important in the development
      of resistances to beta-lactams. STUDY DESIGN: Retrospective review. METHODS: In
      this study, we investigated the mutations in pbp1a, pbp2x, and pbp2b genes
      evaluated by polymerase chain reaction (PCR) in 866 pneumococcal isolates
      collected from the nasopharynx of Japanese children with acute otitis media.
      RESULTS: 210 strains (24.3%) exhibited no mutations in the three pbp genes. 333
      strains (38.5%) had mutations in the three pbp genes, 78 (9.0%) in two pbp genes,
      whereas 245 (28.3%) displayed mutations in only one pbp gene. Among the 656
      strains with mutations in pbp genes, 620 (94.5%) strains had mutations in pbp2x.
      The annual prevalence of antimicrobial-resistant S. pneumoniae showed a gradual
      increase in strains with mutations in the three pbp genes and a parallel decrease
      in strains without mutations. CONCLUSIONS: PCR-based genotyping can characterize
      the antimicrobial resistances in pneumococci along with minimal inhibitory
      concentrations (MICs). Physicians should pay attention to the recent increase in
      antimicrobial-resistant S. pneumoniae when treating pediatric acute otitis media.

PMID- 16462150
TI  - Comparison of uvulopalatopharyngoplasty, laser-assisted uvulopalatoplasty and
      cautery-assisted uvulopalatoplasty in the treatment of primary snoring.
AB  - OBJECTIVE: Our aim was to compare the postoperative pain and surgical results of
      uvulopalatopharyngoplasty (UPPP), laser-assisted uvulopalatoplasty (LAUP), and
      cautery-assisted uvulopalatoplasty (CAUP) procedures in the treatment of primary
      snoring. METHODS: 54 patients were stratified according to a modified Friedman
      staging system (MFSS) for sleep-disordered breathing. Tonsil size (1, 2, 3) and
      palatal position scale (grade 1-2) and body mass index <30 according to the MFSS
      were included for standardization. Three workgroups consisting of 18 patients
      each were formed and UPPP, LAUP and CAUP procedures were performed. The success
      of the surgical procedures was evaluated by applying the Epworth Sleepiness Scale
      to the patients, and the patients' bed partners were asked to evaluate the
      snoring level preoperative and 45 days after the operation to determine any
      improvement in snoring complaints. Patients were followed for postoperative pain,
      secondary infection, bleeding, permanent velopharyngeal insufficiency and
      nasopharyngeal stenosis. RESULTS: Snoring was relieved in 83.3% of UPPP and CAUP
      groups and in 88.8% of LAUP 45 days after operation. The mean pain duration was
      5.71 days for the UPPP patients, 6.28 days for the LAUP patients and, 4.12 days
      for the CAUP patients. The mean pain score was 2.1 for the UPPP patients, 2.38
      for the LAUP patients, and 1.6 for the CAUP patients. Only 1 patient was
      hospitalized due to pain in the LAUP group. CONCLUSION: The effectiveness of
      UPPP, LAUP and CAUP procedures were found to be similar (more than 83%).
      Postoperative pain was mostly seen in LAUP and UPPP cases. The CAUP procedure was
      easy and the least painful.

PMID- 16462151
TI  - Advances in the recognition of tubal intraepithelial carcinoma: applications to
      cancer screening and the pathogenesis of ovarian cancer.
AB  - Prophylactic salpingo-oophorectomies from women with BRCA mutations (BRCA+) have
      identified the tube as a frequent site of early pelvic serous carcinoma (tubal
      intraepithelial carcinoma [TIC]). These observations have implications for both
      the early recognition of pelvic serous carcinoma in susceptible women and
      determining the ultimate site of origin for pelvic serous carcinomas. Moreover,
      the unique pathology of TIC has shifted attention from the more exuberant
      proliferations mentioned in prior studies to a spectrum of neoplastic atypias
      that can be morphologically subtle. This review addresses a multitude of
      epithelial changes; benign, malignant, and an intriguing third group, which we
      term "p53 signatures," is found in benign, nonciliated epithelium and stain
      intensely positive for p53. Understanding all 3 is important for the proper
      management of women undergoing prophylactic salpingo-oophorectomy and possibly
      formulating an integrated model for the pathogenesis of serous carcinoma in the
      reproductive tract. A protocol for sectioning and extensively examining the
      fimbriated end (SEE-FIM), and its rationale, is described.

PMID- 16462152
TI  - p16 expression in the female genital tract and its value in diagnosis.
AB  - p16 is a cyclin-dependent kinase-4 inhibitor that is expressed in a limited range
      of normal tissues and tumors. In recent years, immunohistochemistry with p16
      antibodies has been used as a diagnostic aid in various scenarios in gynecologic
      pathology. Diffuse (as opposed to focal) positivity with p16 in the cervix can be
      regarded as a surrogate marker of the presence of high-risk human papillomavirus
      (HPV). In cervical squamous lesions, p16 is positive in most high-grade cervical
      intraepithelial neoplasia (CIN) and in some cases of low-grade CIN, usually those
      associated with high-risk HPV. p16 may be useful to identify small focal high
      grade CIN lesions, to distinguish some cases of CIN involving immature
      metaplastic squamous epithelium from immature metaplastic squamous epithelium not
      involved by CIN and to distinguish high-grade CIN from benign mimics. Most
      cervical carcinomas of squamous, glandular, and small cell type are p16-positive.
      In cervical glandular lesions, p16 is useful, as part of a panel, in the
      distinction between adenocarcinoma in situ (diffusely positive) and benign
      mimics, including tuboendometrial metaplasia and endometriosis, which are usually
      p16-negative or focally positive. p16 may be used, in combination with other
      markers, to distinguish between a cervical adenocarcinoma (diffuse positivity)
      and an endometrioid-type endometrial adenocarcinoma (negative or focally
      positive). Some uterine serous carcinomas are diffusely positive. In the vulva,
      p16 is positive in HPV-associated vulval intraepithelial neoplasia (VIN) but
      negative in VIN not associated with HPV. Similarly, HPV-associated invasive
      squamous carcinomas are p16-positive, whereas the more common non-HPV-associated
      neoplasms are largely negative or focally positive. In the uterus, p16 positivity
      is more common and widespread in leiomyosarcomas than leiomyomas, and this may be
      a useful aid to diagnosis, although problematic uterine smooth muscle neoplasms
      have not been extensively studied. Metastatic cervical adenocarcinomas in the
      ovary are usually diffusely p16-positive, and because these may closely mimic a
      primary ovarian endometrioid or mucinous adenocarcinoma, this may be a valuable
      diagnostic aid, although p16 expression in primary ovarian adenocarcinomas of
      these morphologic subtypes has not been widely investigated. Some ovarian serous
      carcinomas, similar to their uterine counterparts, are p16-positive.

PMID- 16462153
TI  - Value of immunohistochemistry in distinguishing peritoneal mesothelioma from
      serous carcinoma of the ovary and peritoneum: a review and update.
AB  - At present, a large number of immunohistochemical markers that can be used in the
      differential diagnosis between epithelioid peritoneal mesotheliomas and serous
      carcinomas are available. However, great differences of opinion exist regarding
      the individual value of some of these markers. This article provides a critical
      review of all of the information that is currently available on those markers
      that have the greatest potential for assisting in distinguishing between
      peritoneal mesotheliomas and serous carcinomas. The conclusion of this review
      indicates that the positive serous carcinoma markers, by and large, have a higher
      degree of sensitivity and specificity in assisting in discriminating between
      these malignancies than the positive mesothelioma markers. From a practical point
      of view, a combination of MOC-31 (or Ber-EP4), estrogen receptors, and calretinin
      immunostaining should allow a clear distinction to be made between epithelioid
      peritoneal mesotheliomas and serous carcinomas in most cases.

PMID- 16462155
TI  - Update on the Gleason grading system for prostate cancer: results of an
      international consensus conference of urologic pathologists.
AB  - The Gleason system for prostate cancer was based on a study of 270 patients from
      the Minneapolis Veterans Administration Hospital in 1966-1967. In 1974, Gleason
      and the Veterans Administrative Cooperative Urological Research Group expanded
      this study to 1032 men. These studies formed the basis of the Gleason grading
      system, which is now endorsed as the primary grading system for prostate cancer
      by the World Health Organization, the Armed Forces Institute of Pathology
      Fascicle on prostate cancer, the Association of Directors of Anatomic and
      Surgical Pathology, and the College of American Pathologists. In the nearly 40
      years since its inception, several aspects about prostate cancer and its
      management have changed, most notably serum prostate-specific antigen,
      transrectal ultrasonography, 18-gauge needle biopsy sampling,
      immunohistochemistry for the diagnosis of cancer, and radical prostatectomy and
      radiation therapy as primary treatment modalities. Several aspects of the
      disease, and consequently the reporting needs, have changed such as reporting
      cancer on multiple cases in needle biopsies, multiple nodules in prostatectomy,
      tertiary patterns, variants and variations in prostate cancer. The application of
      the Gleason system, therefore, has varied considerably in contemporary surgical
      pathology practice. An International Consensus Conference attended by 80 urologic
      pathologists from 20 countries was convened to discuss clarifications and
      modifications to the Gleason system. This article serves as a brief overview and
      summary of the proceedings that have been published in detail in recent
      literature.

PMID- 16462154
TI  - Renal cystic diseases: a review.
AB  - This review aims to assist in the categorization of inherited, developmental, and
      acquired cystic disease of the kidney as well as to provide a pertinent, up-to
      date bibliography. The conditions included are autosomal-dominant polycystic
      kidney disease, autosomal-recessive polycystic kidney disease, unilateral renal
      cystic disease (localized cystic disease), renal simple cysts, multicystic
      dysplastic kidney, pluricystic kidney of the multiple malformation syndromes,
      juvenile nephronophthisis and medullary cystic disease, medullary sponge kidney,
      primary glomerulocystic kidney disease, and glomerulocystic kidney associated
      with several systemic disorders mainly of genetic or chromosomal etiology, cystic
      kidney in tuberous sclerosis, and in von Hippel-Lindau syndrome, cystic nephroma,
      cystic variant of congenital mesoblastic nephroma, mixed epithelial stromal tumor
      of the kidney, renal lymphangioma, pyelocalyceal cyst, peripylic cyst and
      perinephric pseudocyst, acquired renal cystic disease of long-term dialysis, and
      cystic renal cell carcinoma and sarcoma. Whereas the gross and histologic
      appearance of some of these conditions may be diagnostic, clinical and sometimes
      molecular studies may be necessary to define other types.

PMID- 16462156
TI  - Pathology and the internet.

PMID- 16462162
TI  - Molecular biology of the small intestine.
AB  - PURPOSE OF REVIEW: A concise report of published research is presented here that
      has provided new insights into the molecular and cell biology of the small
      intestine. RECENT FINDINGS: The precise control of cell renewal lineage
      commitment, differentiation and apoptosis along the crypt-villus axis are
      regulated by paracrine and autocrine signaling pathways that include Wnt,
      Hedgehog and Notch ligands. The downstream signaling pathways and transcriptional
      control of gene expression are being elucidated. Conditional loss of functional c
      myc in the intestinal mucosa may have no effect on the normal homeostasis of this
      tissue. Manipulation of CUGBP2 expression may modulate the response of normal
      intestine to radiation therapy. SUMMARY: The cellular interactions at various
      levels in the small intestine are being understood and would provide a framework
      for interventional translational research in coming years.

PMID- 16462161
TI  - Regulation of the intestinal epithelial barrier by the apical junctional complex.
AB  - PURPOSE OF REVIEW: Epithelial intercellular junctions are important components of
      the epithelial barrier and are compromised in disorders such as Crohn's disease.
      We will highlight recent progress in understanding the role of an intercellular
      junction referred to as the apical junctional complex in regulating small
      intestinal epithelial permeability in health and disease. RECENT FINDINGS: Recent
      studies have implicated aberrant regulation of the AJC as an underlying factor
      contributing to a leaky epithelial barrier in Crohn's patients. Consequences of
      increased epithelial permeability include exposure of intestinal tissue to
      luminal antigens/pathogens which in turn influence disease activity. Furthermore,
      proinflammatory cytokines released into the milieu of the epithelium in patients
      with Crohn's disease influence apical junctional complex and epithelial barrier
      function. Such cytokines induce disassembly of the apical junctional complex by
      promoting differential endocytosis of component proteins. Additionally, apical
      junctional complex proteins are targeted by pathogens that use the epithelium as
      a portal of entry to establish disease in the host. SUMMARY: The epithelial
      apical junctional complex is important in determining epithelial barrier
      properties. Recent studies have highlighted contribution of proinflammatory
      cytokines and endocytosis of apical junctional complex proteins to the epithelial
      barrier defect. Continued advances in understanding of this field will yield new
      therapeutic targets for intestinal disorders.

PMID- 16462164
TI  - Enteric nervous system.
AB  - PURPOSE OF REVIEW: Our aim was to provide a synopsis of how the field of enteric
      neurobiology has advanced during the past year. RECENT FINDINGS: With such a
      large number of studies to choose from and given our emphasis in last year's
      issue on developmental aspects of the enteric nervous system, we have focused on
      several key themes reflecting the current interest in the way the enteric nervous
      system is altered in disease. SUMMARY: The new basic science information gathered
      during the past year provides insight into pathophysiological processes and will
      pave the way for improved understanding of both organic and 'functional'
      gastrointestinal disorders.

PMID- 16462165
TI  - Small intestinal motility.
AB  - PURPOSE OF REVIEW: To review recently published studies presenting novel and
      relevant information on small intestinal motility in humans and animals. RECENT
      FINDINGS: Mechanisms of intestinal dysmotility in patients with pseudoobstruction
      and colonic inertia are becoming better clarified. The role of enteric flora in
      health and disease is an important and rapidly evolving area that will no doubt
      yield significant advances in the evaluation and treatment of many digestive
      disorders. The role of bacterial overgrowth in irritable bowel syndrome requires
      further study. The mechanisms underlying postoperative ileus are becoming both
      better understood and increasingly complex. Peripheral opioid antagonists may
      represent an important therapeutic advance in the treatment of ileus.
      Cannabinoids also appear to play a role in ileus and this echoes our rapidly
      evolving understanding of these compounds in the regulation of motility. SUMMARY:
      Small intestinal motility remains an understudied area. Recent publications have
      shed additional light on myogenic, neural, and hormonal control mechanisms.

PMID- 16462163
TI  - Sensor molecules in intestinal innate immunity against bacterial infections.
AB  - PURPOSE OF REVIEW: Toll-like receptors (TLRs) and nucleotide-binding
      oligomerization domain (NOD)-containing proteins are innate immune sensors for
      microbial signature molecules. This review highlights new insights into the
      functions of these sensors in intestinal physiology. RECENT FINDINGS: TLRs are
      membrane bound and survey the extracellular space for microbe-derived molecules,
      while NOD-containing proteins are cytoplasmic and detect microbial molecules in
      the cytoplasm. Most microbial sensors recognize components of the bacterial cell
      wall and its appendages. For example, TLR4 detects lipopolysaccharide in the Gram
      negative bacterial cell wall. TLR5 recognizes flagellin, a component of bacterial
      flagella required for motility. NOD1 recognizes diaminopimelic acid-containing
      dipeptide or tripeptide motifs in the Gram-positive bacterial cell wall, while
      NOD2 detects muramyl dipeptide, a ubiquitous cell wall peptidoglycan motif. These
      sensors are important for host defense against gastrointestinal pathogens. Thus,
      TLR4 is required for Salmonella eradication, NOD1 contributes to controlling
      Helicobacter pylori infection, and NOD2 is involved in mucosal defense against
      Listeria monocytogenes. These sensors also regulate mucosal inflammation
      independent of pathogen infections. SUMMARY: Toll-like receptors and nucleotide
      binding oligomerization domain-containing proteins not only play critical roles
      in host defense against known gastrointestinal bacterial pathogens, but also
      contribute to mucosal homeostasis in the apparent absence of such pathogens.

PMID- 16462166
TI  - Advances in celiac disease.
AB  - PURPOSE OF REVIEW: This article primarily aims to review critically research in
      all aspects of celiac disease over the last year. As always, there has been a
      wealth of relevant papers. RECENT FINDINGS: The role of genetics in disease
      susceptibility is slowly becoming more clearly defined and a more detailed
      understanding of the disease processes at the molecular level is paving the way
      towards the development of specific targeted therapies. SUMMARY: Despite recent
      advances in our understanding of celiac disease, the gluten-free diet remains the
      only current viable therapy and even with advances in serological tests and
      markers, the duodenal biopsy remains the gold standard for diagnosis and
      monitoring of the response to therapy.

PMID- 16462167
TI  - Video capsule endoscopy of the small bowel (PillCam SB).
AB  - PURPOSE OF REVIEW: It is 4 years since capsule endoscopy was first introduced.
      This disposable 27 mm x 11 mm video capsule containing its own optical dome,
      light source, batteries, transmitter and antenna is swallowed with water after a
      12 h fast. The capsule is propelled via peristalsis through the gastrointestinal
      tract, capturing about 60 000 digital images and is excreted naturally. In a
      relatively short period, capsule endoscopy has become an important investigative
      tool in patients with occult gastrointestinal bleeding, suspected small bowel
      tumors and other abnormalities. The aim of this review is to update the reader
      with the main indications, performance and complications of the technique. RECENT
      FINDINGS: There are some clear indications for capsule endoscopy: occult
      gastrointestinal bleeding, suspected small bowel tumor, suspected Crohn's
      disease, surveillance of inherited polyposis syndromes, drug-induced small bowel
      injury or any abnormal small bowel imaging. Problematic areas include defining
      what are normal findings and the inability to take biopsies and thus
      differentiate between entities. SUMMARY: Capsule endoscopy has become a first
      line tool to detect abnormalities in the small bowel, and is superior to all
      other imaging technologies. Its interplay with the new technique of double
      balloon enteroscopy enables the small bowel to receive proper attention, similar
      to other gastrointestinal organs.

PMID- 16462168
TI  - Irritable bowel syndrome: new and emerging therapies.
AB  - PURPOSE OF REVIEW: Irritable bowel syndrome refers to abdominal discomfort
      associated with altered bowel habits. Recent evidence suggests that the primary
      pathophysiologic mechanism is brain-gut dysregulation. Many central and
      peripheral factors are involved. This article will review important
      pathophysiologic mechanisms with a focus on new and emerging therapies. RECENT
      FINDINGS: Prior gastroenteritis and small intestinal bacterial overgrowth may be
      important for treatment of irritable bowel syndrome. Understanding of
      serotonergic receptors in gastrointestinal function has led to the development of
      serotonergic agents such as alosetron and tegaserod. Novel agents targeting other
      receptor sites include neurokinin and neurohormonal modulators, chloride channels
      and opioid receptors. Other therapeutic approaches - behavioral treatments,
      probiotics, antibiotics and alternative therapies - have developing roles in the
      treatment of irritable bowel syndrome. SUMMARY: A better understanding of
      pathophysiologic mechanisms has resulted in therapeutic advances. Prokinetic
      therapies may have a role in nondiarrhea predominant irritable bowel syndrome.
      Antidepressants are used to modulate pain and treat comorbid psychological
      distress. Newer agents target various receptor sites. Advances in
      psychological/behavioral treatments and alternative modalities hold promise for
      the future.

PMID- 16462169
TI  - Diet and irritable bowel syndrome.

PMID- 16462170
TI  - Intestinal absorption of water-soluble vitamins: an update.
AB  - PURPOSE OF REVIEW: The molecular biology revolution has led to a significant
      improvement in our understanding of biological and physiological processes. Such
      expansion of knowledge has also covered the field of intestinal absorption of
      water-soluble vitamins and is the subject of this review. RECENT FINDINGS:
      Impressive progress has been made in the understanding of the mechanisms and
      regulation of transport of water-soluble vitamins at the cellular and molecular
      levels. In addition, the 5' regulatory regions of the genes that encode a number
      of the involved transporters have been cloned and characterized in vitro and in
      vivo in transgenic mice, thus providing important information about
      transcriptional regulation of these events. Furthermore, confocal imaging of live
      intestinal epithelial cells has led to significant progress in understanding the
      mechanisms involved in intracellular trafficking and membrane targeting of the
      carrier proteins and how clinical mutations lead to interference with transport.
      Finally, the identification in the large intestine of efficient and specialized
      carrier-mediated systems that are capable of absorbing a number of the
      bacterially synthesized vitamins (thiamin, folate, biotin, riboflavin,
      pantothenic acid) has raised the possibility that this source of vitamins may
      play a role in regulating (fine tuning) the normal body homeostasis of these
      vitamins, and especially the vitamin level in the local colonocytes. SUMMARY:
      Water-soluble vitamin absorption involves regulated and specific mechanisms.
      Interference with the function of these mechanisms may lead to deficiency. The
      large intestine is capable of absorbing water-soluble vitamins that are
      synthesized by the normal microflora.

PMID- 16462171
TI  - Eosinophilic esophagitis: treatment in 2005.
AB  - PURPOSE OF REVIEW: Eosinophilic esophagitis is an isolated, eosinophilic
      inflammation of the esophagus. The symptoms are often confused for those of
      gastroesophageal reflux. Over the past few years, there has been a significant
      increase in the literature surrounding eosinophilic esophagitis as more than two
      thirds of the articles written on the subject have been published within the past
      3 years. Because the incidence is rising and the condition is easily diagnosed by
      endoscopy with biopsy, it is important for physicians to understand the
      pathophysiology, clinical presentation, and treatment options available for
      patients. RECENT FINDINGS: The etiology of eosinophilic esophagitis in children
      is reported to be associated with an allergic response to food antigens. Because
      allergy tests are often unable to determine the causative foods, complete
      elimination of all foods is often required. The diagnosis requires a biopsy of
      the esophagus, stomach and duodenum. The condition is diagnosed if the patient's
      esophageal biopsy depicts over 20 eosinophils per high-powered field despite the
      use of aggressive acid blockade, biopsies of the stomach antrum and duodenum are
      normal, and the tissue inflammation resolves when dietary antigens are removed
      from the diet. While the most commonly involved foods causing eosinophilic
      esophagitis include milk, eggs, nuts, beef, wheat, fish, shellfish, corn and soy,
      almost all foods have been implicated. Alternative treatments include esophageal
      dilatation and medical therapy. SUMMARY: This article reviews the past year's
      literature, concentrating on the pathophysiology, and treatment of eosinophilic
      esophagitis in both children and adults.

PMID- 16462172
TI  - An update on low-carbohydrate, high-protein diets.
AB  - PURPOSE OF REVIEW: The use of low-carbohydrate diets in weight loss is an area of
      great controversy. In recent years, a significant amount of research has been
      conducted to evaluate the efficacy of these diets. This review aims to discuss
      mechanisms of action for weight loss; to assess impact on metabolic parameters
      including insulin sensitivity and cardiovascular risk parameters and to evaluate
      the data regarding safety and effectiveness for weight loss. RECENT FINDINGS:
      Most studies demonstrate that subjects following low carbohydrate diets lose more
      weight over the first 3-6 months than subjects consuming control diets. This
      weight loss is not sustained, however, at 1 year. Carbohydrate controlled diets
      may be associated with increased insulin sensitivity and improved glycemic
      control. High carbohydrate, low fat diets appear to have a more favorable impact
      on total and LDL cholesterol, whereas low carbohydrate diets have been shown to
      significantly decrease triglyceride and increase HDL cholesterol levels in short
      term studies. SUMMARY: Low carbohydrate diets may be effective in helping people
      to lose weight. More long-term studies need to be performed, however, to better
      evaluate efficacy, safety, and impact on metabolic profile.

PMID- 16462173
TI  - Parenteral nutrition.
AB  - PURPOSE OF REVIEW: During the past 12 months there have been clinically important
      advances in intravenous nutrition and adjunctive therapies. RECENT FINDINGS:
      Useful steps have been taken in the understanding of the altered physiology of
      the intravenously fed patient, the potential for specific gains from manipulation
      with gut hormones, and avoidance of complications from amended lipid emulsions.
      The role of the nutrition team and the place of IVN in malignancy have also been
      addressed. SUMMARY: Glucagon-like peptide-2, and lipid emulsions based less on
      soy-bean oil appear safe and effective. Euglycaemia is recommended at all times,
      but not too much vitamin C. Long-term intravenous nutrition in cancer patients
      can be justified, and hospital nutrition teams are probably cost-effective.

PMID- 16462175
TI  - Bibliography. Current world literature. Small intestine.

PMID- 16462174
TI  - Polyphenols and gastrointestinal diseases.
AB  - PURPOSE OF REVIEW: This article will review the role of polyphenols in
      gastrointestinal diseases. Ingested polyphenols are concentrated in the
      gastrointestinal tract and are not well absorbed into the rest of the body. Thus,
      the high luminal concentrations achieved support a potential for therapeutic uses
      in the gastrointestinal tract. Additionally, there is great interest from the
      general public in complementary and alternative medicine. RECENT FINDINGS:
      Dietary polyphenols are a major source of antioxidants consumed by humans.
      Polyphenols possess not only antioxidant properties but also antiviral,
      antibacterial, antiinflammatory and anticarcinogenic effects, as well as the
      ability to modulate certain signaling pathways such as nuclear factor-kappaB
      activation. Green tea polyphenols have been shown to have efficacy in various
      models of inflammatory bowel disease. Silymarin, or milk thistle, is
      hepatoprotective against many forms of experimental liver injury and is widely
      used in human liver diseases, such as hepatitis C and alcoholic cirrhosis, with
      an excellent safety profile (but with unclear efficacy). SUMMARY: Substantial in
      vitro and animal studies support the beneficial effects of polyphenols in many
      gastrointestinal diseases. Well designed multicenter trials in humans, such as
      those called for in the 2005 National Institutes of Health Requests for
      Applications for Silymarin Centers, will be critical for defining the safety,
      appropriate dosing and therapeutic efficacy of such agents.

PMID- 16462177
TI  - Donor leukocyte infusions after unrelated donor hematopoietic stem cell
      transplantation.
AB  - PURPOSE OF REVIEW: Donor leukocyte infusions provide direct and potent graft
      versus-tumor activity to treat relapse after allogeneic stem cell
      transplantation. Extensive data are available on the use of donor leukocyte
      infusion after matched-sibling stem cell transplantation, but reports are
      remarkably few on the use of donor leukocyte infusion after unrelated-donor stem
      cell transplantation. But the role for unrelated-donor leukocyte infusion is not
      well established. RECENT FINDINGS: The dramatic success of donor leukocyte
      infusion to treat relapse after matched-sibling stem cell transplantation has led
      to the use of unrelated-donor leukocyte infusion in many patients. Several case
      studies suggest that unrelated-donor leukocyte infusion effectively induces
      direct graft-versus-tumor reactions with toxicity comparable to that of matched
      sibling donor leukocyte infusion. Important issues include the relationship
      between dose and response/toxicity appropriate timing, dose, and schedule; and
      identification of the best tumor targets. In particular nonmyeloablative
      transplant strategies using unrelated donors are expanding rapidly, but relapse
      rates are high. There is a paucity of data on unrelated-donor leukocyte infusion
      in this setting. SUMMARY: This review summarizes recent data on the use of
      unrelated-donor leukocyte infusion. We discuss anticipated outcomes and identify
      areas under active investigation in both ablative and nonmyeloablative unrelated
      donor stem cell transplantation.

PMID- 16462178
TI  - Hematopoietic stem cell transplant-related airflow obstruction.
AB  - PURPOSE OF REVIEW: Airflow obstruction is a rare but fatal complication following
      allogeneic hematopoietic stem cell transplantation. It is noninfectious,
      relatively late, and primarily affects small airways, ultimately leading to their
      obliteration. If airflow obstruction is consistent with obliteration
      histologically, the condition is often called bronchiolitis obliterans. This
      review of literature published recently evaluates progress made in this field.
      RECENT FINDINGS: Changes reported in analysis of pulmonary function test results
      and their follow-up might be helpful to better manage bronchiolitis obliterans
      and to detect and treat it earlier. Graft-versus-host reaction possibly underlies
      the development of this fatal disease. Findings from high-resolution computed
      tomography might aid in the diagnostic process. Anti-inflammatory therapy,
      azithromycin and lung transplant might be an option to treat bronchiolitis
      obliterans. SUMMARY: The pathomechanism of bronchiolitis obliterans remains
      unclear and it remains a fatal complication of hematopoietic stem cell
      transplantation. An appropriate model to study hematopoietic stem cell
      transplantation-related airflow obstruction, consensus diagnostic criteria, and
      prospective trials for treatment are necessary to overcome the challenge
      presented by bronchiolitis obliterans.

PMID- 16462179
TI  - Update on the management of acute graft-versus-host disease.
AB  - PURPOSE OF REVIEW: Acute graft-versus-host disease is one of the commonest
      complications after allogeneic stem cell transplantation. Recent advances in its
      prevention and therapy are giving new hope to patients with this disease. This
      review covers the major advances in prophylaxis and therapy for this problem.
      RECENT FINDINGS: The use of novel approaches for prophylaxis such as
      posttransplant cyclophosphamide and non-methotrexate-containing regimens is
      discussed. The results of therapy with new agents such as pentostatin, pulse
      cyclophosphamide, long-wavelength ultraviolet A phototherapy, and monoclonal
      antibodies such as denileukin diftitox or etanercept are reviewed. SUMMARY:
      Without question, outcome in patients who develop graft-versus-host disease is
      improving. With better supportive care, and more effective prophylaxis and
      therapy, these patients have an improved chance for full recovery. Patients
      should be enrolled, when possible, in studies aimed to prevent and treat graft
      versus-host disease.

PMID- 16462180
TI  - Chronic graft-versus-host disease.
AB  - PURPOSE OF REVIEW: Chronic graft-versus-host disease is an important cause of
      late morbidity and mortality after allogeneic stem cell transplantation. With the
      renewed interest in its pathophysiology and treatment, this review discusses
      recent clinical and laboratory advances in this disease. Advances in
      pathophysiology, the relationship between chronic graft-versus-host disease and
      relapse incidence, and recent developments in the prophylaxis, initial therapy,
      and therapy for refractory disease are discussed. RECENT FINDINGS: A better
      understanding of the pathophysiology of chronic graft-versus-host disease,
      including the potential role of a coordinated B-cell and T-cell response, is
      demonstrated. Corticosteroids and cyclosporine or tacrolimus remain the standard
      as initial therapy. This combination is effective in the majority of affected
      patients, although therapy is often required for longer than 1 year. Although no
      strategy has been demonstrated to be effective in specifically preventing chronic
      graft-versus-host disease, several drugs have recently been demonstrated to be
      effective therapeutic agents for steroid-refractory disease. Agents such as
      mycophenolate mofetil, sirolimus, and rituximab have demonstrated response rates
      of greater than 60% in patients with steroid-refractory disease. SUMMARY: Renewed
      interest and understanding of chronic graft-versus-host disease have led to novel
      treatment strategies for steroid-refractory disease. A focus on the initial
      therapy and prophylaxis against chronic graft-versus-host disease is now
      warranted.

PMID- 16462181
TI  - Targeted therapies and non-small-cell lung cancer: work in progress?

PMID- 16462182
TI  - Treatment of non-small-cell lung cancer and pharmacogenomics: where we are and
      where we are going.
AB  - PURPOSE OF REVIEW: This review highlights the numerous molecular biology findings
      in the field of lung cancer with potential therapeutic impact in both the near
      and distant future. RECENT FINDINGS: Abundant preclinical and clinical data
      indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy
      sensitivity. Single nucleotide polymorphisms in the excision repair cross
      complementing 1 gene (ERCC1) influence survival with cisplatin-based
      chemotherapy. For the first time, epidermal growth factor receptor (EGFR)
      mutations have been shown to predict dramatic responses in metastatic lung
      adenocarcinomas. The crosstalk between estrogen and EGFR pathways have also been
      revealed. MicroRNAs control the expression of cognate target genes and predict
      relapse in surgically resected non-small-cell lung cancer patients.
      Overexpression of the Wingless-type (Wnt) genes and methylation of Wnt
      antagonists have been documented in non-small-cell lung cancer. SUMMARY:
      Understanding the relevance of these findings can help to change the clinical
      practice in oncology towards customizing chemotherapy and targeted therapies,
      leading to improvement both in survival and in cost-effectiveness.

PMID- 16462183
TI  - Advances in our understanding of postoperative adjuvant chemotherapy in
      resectable non-small-cell lung cancer.
AB  - PURPOSE OF REVIEW: After publication in 1995 of a meta-analysis of adjuvant
      chemotherapy in the treatment of NSCLC, a number of randomized trials
      investigated adjuvant chemotherapy using more active chemotherapeutic regimens
      and larger numbers of accrued patients per trial. This review will focus on
      recent clinical trials for adjuvant chemotherapy, and will help to interpret the
      applicability of these results to daily clinical practice. RECENT FINDINGS: Four
      large-scale randomized trials that used platinum-based chemotherapy have reported
      positive results during the last 3 years. These trials included cisplatin-based
      chemotherapy [the International Adjuvant Lung Cancer (IALT) trial], cisplatin
      plus vinorelbine [the National Cancer Institute of Canada (NCIC) BR10 trial], and
      carboplatin plus paclitaxel [the Cancer and Leukemia Group B (CALGB) 9633 trial].
      More recently, another adjuvant trial [Adjuvant Navelbine International Trialist
      Association (ANITA)] was reported, which has added greatly to our understanding
      of the potential role of adjuvant treatment. Regarding adjuvant UFT (tegafur and
      uracil) chemotherapy, an individual patient data-based meta-analysis demonstrated
      its significant effect on survival in selected patients with completely resected
      non-small-cell lung cancer. SUMMARY: Recent trials indicate a survival benefit of
      postoperative adjuvant chemotherapy. These findings are anticipated to change the
      clinical management of patients with completely resectable non-small-cell lung
      cancer.

PMID- 16462184
TI  - Antiangiogenic drugs in non-small cell lung cancer treatment.
AB  - PURPOSE OF REVIEW: A promising therapeutic target is the vascular endothelial
      growth factor pathway - a key mediator of tumor angiogenesis - which is important
      in tumor growth, invasion, and metastasis. This review focuses on the available
      clinical data on drugs targeting the vascular endothelial growth factor -
      vascular endothelial growth factor receptor pathway in the treatment of non-small
      cell lung cancer. RECENT FINDINGS: The therapeutic value of inhibiting the
      vascular endothelial growth factor pathway has been demonstrated by using drugs
      that prevent vascular endothelial growth factor receptor binding and by using
      drugs that inhibit receptor activation. Two antiangiogenic drugs exemplify these
      mechanisms: bevacizumab (Avastin; Genentech, South San Francisco, California,
      USA), a humanized monoclonal antibody that acts by binding and neutralizing
      vascular endothelial growth factor; and ZD6474 (Zactima; AstraZeneca,
      Macclesfield, UK), a small-molecule inhibitor of vascular growth factor receptor
      and epidermal growth factor receptor tyrosine kinase activity. Recently, the
      first results of a large, phase III randomized clinical trial of bevacizumab in
      combination with platinum-based doublet chemotherapy have been reported in
      patients with nonsquamous non-small cell lung cancer. SUMMARY: The inhibition of
      tumor angiogenesis is a key therapeutic strategy that holds great promise for the
      advancement of metastatic lung cancer therapy. The combination of bevacizumab and
      conventional chemotherapy could offer a new therapeutic option in selected non
      small cell lung cancer histotypes.

PMID- 16462186
TI  - Current and evolving treatment options for limited stage small cell lung cancer.
AB  - PURPOSE OF REVIEW: About one-third of small cell lung cancer cases are classified
      as limited stage. Trials have attempted to establish the most effective, least
      toxic regimen of combined modality treatment. Recently, issues like the role of
      the positron emission tomography scan, elderly patient management and the timing
      and delivery of radiotherapy have been addressed. Several targeted agents have
      also been evaluated. This review will highlight the data that have greatly
      impacted on the standard of limited stage small cell lung cancer care. RECENT
      FINDINGS: Trials have concluded that small cell lung cancer is fluorodeoxy-D
      glucose avid and that positron emission tomography has potential for utility in
      staging and radiation therapy planning, though it is not recommended. Recent
      trials confirm no benefit to adding chemotherapeutic agents to standard cisplatin
      and etoposide. To date, all targeted therapies have failed to show impressive
      results. Two analyses of outcomes in elderly patients argue that combined
      modality therapy should be considered, with patients carefully monitored. Two
      meta-analyses demonstrate thoracic radiotherapy should be delivered, with
      increased dose and schedule intensity. SUMMARY: Current data demonstrate that
      combined modality therapy with early administration of thoracic radiotherapy
      remains the care standard in limited stage small cell lung cancer care. Cisplatin
      and etoposide continue to be the chosen cytotoxic agents. Targeted therapies and
      advances in the radiotherapy technological aspects represent opportunities for
      improved outcomes in the future management of this aggressive disease.

PMID- 16462187
TI  - Melanoma genetics: a review of genetic factors and clinical phenotypes in
      familial melanoma.
AB  - PURPOSE OF REVIEW: The clinical phenotypes of familial melanoma syndromes and
      genetic and environmental interactions are reviewed to summarize the current
      status of the field and to identify gaps in molecular and clinical
      investigations. RECENT FINDINGS: The familial melanoma syndromes are associated
      with germline mutations in three highly penetrant gene products: p16, alternate
      reading frame, and cyclin-dependent kinase 4. Certain variants in a low
      penetrance gene, MC1R, the melanocortin 1 receptor gene, increase melanoma risk
      to a lesser extent and act as a genetic modifier when cosegregating with a
      deleterious p16 gene. The penetrance of these melanoma-predisposing genes is
      largely influenced by ultraviolet exposure across geographic latitude. Yet
      cumulative studies are conflicting on whether ultraviolet radiation, including
      sunburns, early childhood and adolescent sun exposure, and chronic exposure,
      increases melanoma risk in familial melanoma. To date, the clinical phenotypes of
      increased number of atypical nevi and nevi body distribution are independent risk
      factors for melanoma risk, regardless of family history. The atypical mole
      syndrome cannot reliably predict melanoma germline mutations but increases
      melanoma risk in p16 mutation carriers. Familial melanoma patients develop
      melanomas earlier and are prone to developing multiple primary melanomas. Other
      than these two differences, familial and sporadic melanoma share similar
      histopathology, prognostic factors, and survival rates. SUMMARY: Familial
      melanoma is an excellent human model system for the investigation of melanoma.
      Understanding genotype-phenotype and environmental relationships in familial
      melanoma will likely lead to improved understanding of pathogenesis for all
      melanoma patients.

PMID- 16462185
TI  - New developments in chemotherapy for advanced non-small cell lung cancer.
AB  - PURPOSE OF REVIEW: The treatment of patients with advanced non-small cell lung
      cancer has changed considerably in the past decade. This paper reviews the most
      significant changes seen in chemotherapy and the most promising new agents in
      development for this disease. RECENT FINDINGS: Chemotherapy prolongs survival and
      improves quality of life in patients with a good performance status and appears
      to alleviate disease-related symptoms in patients with a lower performance
      status. Platinum-based regimens became standard; none of the third-generation
      drug combinations seemed to be superior to the others. Nonplatinum combinations
      are reasonable alternatives now and offer a better toxicity profile in certain
      populations. Attempts to add molecular-targeted therapy to combination
      chemotherapy have failed except for bevacizumab. New compounds such as
      pemetrexed, bortezomib, TLK286, bevacizumab, and the epothilones are currently
      being evaluated in non-small cell lung cancer. SUMMARY: Management of non-small
      cell lung cancer has improved considerably in the past decade. The overall
      benefit of chemotherapy over supportive care has been shown, platinum-based
      doublets have been established, nonplatinum regimens have been developed,
      chemotherapy has been used more broadly in subgroups of patients who have been
      previously neglected, and a shorter chemotherapy duration has been shown to be
      equally effective. After hitting a plateau in the benefit of chemotherapy, new
      drugs with novel action mechanisms such as the ones described here offer hope to
      improve therapy for this disease.

PMID- 16462188
TI  - What about chemoprevention for melanoma?
AB  - PURPOSE OF REVIEW: This paper aims to critically review the potential for a
      chemoprevention strategy in melanoma, and to discuss new data on candidate
      chemoprevention agents, as chemoprevention has been suggested as an unexplored
      approach in melanoma. RECENT FINDINGS: A strong scientific rationale, established
      long-term safety of candidate agents, and a systematic step-wise approach to
      chemoprevention agent development are all critical for melanoma chemoprevention
      research. Among potential agents, the lipid-lowering drugs, the statins, satisfy
      these prerequisites. SUMMARY: Chemoprevention of cutaneous melanoma can become a
      valid strategy complementing current prevention approaches, as long as these
      important prerequisites are taken into consideration.

PMID- 16462189
TI  - Should all melanoma patients undergo sentinel lymph node biopsy?
AB  - PURPOSE OF REVIEW: It is now well established that sentinel lymph node biopsy is
      a powerful test to predict prognosis for melanoma patients. Controversy exists,
      however, regarding the appropriate selection of patients for sentinel lymph node
      biopsy, especially among patients with thin melanomas (< 1 mm Breslow thickness),
      thick melanomas (> 4 mm Breslow thickness), or locally recurrent melanoma. RECENT
      FINDINGS: The majority of the studies in the past 2 years regarding sentinel
      lymph node biopsy have been concerned with identifying factors that can better
      predict regional nodal metastasis and survival. Other studies have proposed a
      better risk stratification model, which includes these factors, to best select
      those patients at increased risk of nodal positivity. SUMMARY: Although much
      research has been done to select appropriate patients for sentinel lymph node
      biopsy based on multiple prognostic factors, further studies are necessary to
      completely define the indications for this procedure in patients with thin, thick
      and locally recurrent melanomas.

PMID- 16462190
TI  - Apoptosis and melanoma: how new insights are effecting the development of new
      therapies for melanoma.
AB  - PURPOSE OF REVIEW: Melanoma has proven resistant to most available chemotherapy
      and immunotherapy. Despite a range of different biochemical targets, most agents
      kill cancer cells by induction of apoptosis. RECENT FINDINGS: Investigation of
      this process has provided insights into the resistance mechanisms in cancer cells
      and to development of a range of new agents that target apoptosis pathways. These
      include agents which inhibit antiapoptotic B cell lymphoma-2 family proteins and
      inhibitor of apoptosis proteins. In addition, a range of signal pathway
      inhibitors have become available that are able to inhibit signal pathways known
      to be associated with resistance to apoptosis. SUMMARY: Evaluation of most of
      these reagents are at a preclinical level but studies on some pathway inhibitors
      have passed from phase II into phase III studies. Similarly, evaluation of
      antisense reagents are at an advanced stage. These early trials show much promise
      and suggest this approach to development of new therapies will lead to much
      needed advances in treatment of this disease.

PMID- 16462191
TI  - Bibliography. Current world literature.

PMID- 16462194
TI  - Independent component analysis in the distinction between focal and multifocal
      spikes.
AB  - Independent component analysis (ICA) is a novel method that extracts independent
      sources in recorded signals. One of its capabilities is to separate epileptiform
      activity of different origins. The goal of this study was to demonstrate that ICA
      is useful for differentiating focal and multifocal epilepsies. Using ICA, the
      authors analyzed 160 samples of patients with unifocal (temporal: 50 samples from
      5 patients; frontal: 50 samples from 5 patients) or multifocal epilepsy
      (bitemporal: 30 samples from 3 patients; multifocal extratemporal: 30 samples
      from 5 patients). Each sample included at least two spikes. ICA was applied using
      the JADE algorithm implemented in a Matlab platform. The components were
      identified visually. The EEG and the isopotential map of the suspected components
      were reconstructed to demonstrate the nature and location of each spike. In
      multifocal epilepsies, the spikes were separated in distinct components in all
      cases. In unifocal temporal epilepsies, ICA extracted all the spikes from the
      same location into a single component. In the patients with unifocal frontal
      epilepsy, one component included all the spikes in 80% of the samples; in some of
      these cases, other components were responsible for small parts of the spikes, but
      with a close topography to the main component. The waves were separated in
      different components both in the unifocal and in the multifocal samples.
      Therefore, in epilepsies with independent foci, ICA separates the spikes of
      different origins into distinct components. In unifocal epilepsies, ICA tends to
      locate the spikes from the same area into the same component, especially in
      temporal epilepsies. The authors conclude that ICA might be a useful tool to
      distinguish between unifocal and multifocal epilepsies.

PMID- 16462195
TI  - Differentiability of simulated MEG hippocampal, medial temporal and neocortical
      temporal epileptic spike activity.
AB  - Previous studies have shown that magnetoencephalography (MEG) can measure
      hippocampal activity, despite the cylindrical shape and deep location in the
      brain. The current study extended this work by examining the ability to
      differentiate the hippocampal subfields, parahippocampal cortex, and neocortical
      temporal sources using simulated interictal epileptic activity. A model of the
      hippocampus was generated on the MRIs of five subjects. CA1, CA3, and dentate
      gyrus of the hippocampus were activated as well as entorhinal cortex,
      presubiculum, and neocortical temporal cortex. In addition, pairs of sources were
      activated sequentially to emulate various hypotheses of mesial temporal lobe
      seizure generation. The simulated MEG activity was added to real background brain
      activity from the five subjects and modeled using a multidipole spatiotemporal
      modeling technique. The waveforms and source locations/orientations for
      hippocampal and parahippocampal sources were differentiable from neocortical
      temporal sources. In addition, hippocampal and parahippocampal sources were
      differentiated to varying degrees depending on source. The sequential activation
      of hippocampal and parahippocampal sources was adequately modeled by a single
      source; however, these sources were not resolvable when they overlapped in time.
      These results suggest that MEG has the sensitivity to distinguish parahippocampal
      and hippocampal spike generators in mesial temporal lobe epilepsy.

PMID- 16462196
TI  - Enhancements in epilepsy forewarning via phase-space dissimilarity.
AB  - The authors extend the recent application of phase-space dissimilarity measures
      for scalp EEG data in two directions. First, a forewarning window of up to 8
      hours was used, thereby providing more forewarning time of the seizure event.
      This window was limited to a maximum of 1 hour in their previous work. Second,
      they combined information from two channels via a multichannel phase-space to
      improve the quality and confidence limits of the forewarning. Combining these two
      enhancements, they obtained two-channel results that were superior to the single
      channel ones.

PMID- 16462197
TI  - Predictive value of early EEG after epilepsy surgery.
AB  - To determine whether EEG performed within few months after epilepsy surgery is
      predictive of seizure outcome, 58 consecutive patients undergoing surgery for
      presumptive temporal lobe epilepsy (TLE) who had clinical follow-up of at least 2
      years and EEG data available both pre- and postoperatively were analyzed.
      Patients were classified by preoperative brain magnetic resonance imaging into
      lesional, cryptogenic, and hippocampal sclerosis groups. Seizure outcome was
      classified according to Engel's outcome scale. Comparison was made between the
      presence of interictal epileptiform discharges (IEDs) in the postoperative EEG
      and seizure outcome. Patients who experienced seizures within 2 months after
      surgery were considered to have early recurrence. The mean follow-up period was 3
      years. Sixty percent of patients achieved a class I seizure outcome. Almost all
      (95%) postoperative EEGs were obtained within 4 months after surgery. IEDs were
      present in 26% of postoperative EEGs, but were significantly less frequent in
      EEGs recorded after the first two postoperative months (P = 0.011). The presence
      of IEDs on postoperative EEGs was not predictive of seizure outcome either in the
      whole cohort or in any of the subgroups, regardless of whether it was performed
      within or after the first two postoperative months. It was also not predictive of
      outcome in the 44 patients (76%) who did not suffer early recurrence. The authors
      conclude that EEG performed a few months after epilepsy surgery is not useful as
      a predictor of long-term seizure outcome.

PMID- 16462198
TI  - Near-infrared spectroscopy to define cognitive frontal lobe functions.
AB  - Near-infrared spectroscopy (NIRS) monitors changes in the regional cerebral
      oxygenation (rSO) and has been used to study cerebral physiologic functions in
      normal states and during epileptic seizures. Yet, the limitations and pitfalls of
      the technique are not fully understood. The authors evaluated NIRS changes over
      the frontal lobes during language tasks known to be associated with the integrity
      of the dominant frontal lobe in 17 normal adults (handedness: 14 right, 3 left).
      Recording protocol involved a baseline (3 minutes) with the subject relaxed and
      thinking of a blue sky and a second baseline during voluntary mouth movements
      mimicking speech. Two standardized neuropsychological word-generation tasks
      (controlled word-association tests: CFL and Animals) were then administered (4
      minutes total) followed again by the two baseline procedures. Mouth movement
      without verbalization increased rSO values in excess of 2 SD of baseline
      fluctuations in 70% of the subjects. A t-test comparison of these baseline
      measurements was statistically significant (P < 0.0001). A general linear model
      repeated-measures procedure was then used to statistically examine NIRS
      increments during the cognitive tasks above and beyond the contribution produced
      by mouth movements during the second baseline. Compared to the second baseline,
      rSO further increased significantly during the word generation tasks (left
      frontal F value = 21.4, P < 0.0001; right frontal F value = 15.2, P < 0.001),
      confirming the utility of the technique. There was no apparent difference related
      to handedness. These findings corroborate the usefulness of NIRS to demonstrate
      focal cerebral activation during an "executive" language task. However,
      interpretation of changes can be confounded by extracerebral factors such as
      mouth movement, a finding of particular relevance in NIRS clinical applications.

PMID- 16462199
TI  - Crossed inhibition of sensory cortex by 0.3 Hz transcranial magnetic stimulation
      of motor cortex.
AB  - Low-frequency repetitive transcranial magnetic stimulation (rTMS) of motor cortex
      causes persistent inhibitory effects in the targeted area. rTMS of motor cortex
      impairs sensory perception and results in a persistent change in cortical
      function at remote sites. The ability of rTMS to induce sustained changes in
      cortical function has led to studies testing its therapeutic efficacy in
      neurologic disorders, including epilepsy. Studies on the effect of low-frequency
      rTMS of motor cortex on the contralateral motor cortex have provided evidence for
      both inhibitory and excitatory changes. This study was designed to determine the
      effect of low-frequency rTMS of the right motor cortex on the contralateral
      sensory cortex. Before and after 0.3-Hz rTMS of right motor cortex, perception of
      ipsilateral threshold of cutaneous stimuli was assessed and somatosensory evoked
      potentials (SEPs) recorded after stimulation of the right thumb in eight normal
      subjects. In a control group of six subjects, sensory responses were assessed
      after rTMS anterior to the right motor cortex. After rTMS of motor cortex,
      detection of threshold sensory stimuli decreased by more than 50% compared with
      pre-rTMS (P < 0.05). The change in sensory perception lasted at least 30 minutes.
      No change was detected in the control group. Amplitude of the N20-P25 waveform of
      the SEP decreased from a mean of 0.84 muV before rTMS to 0.54 muV immediately
      after rTMS of motor cortex (P < 0.05). 0.3 Hz rTMS of motor cortex inhibits the
      contralateral sensory cortex.

PMID- 16462200
TI  - Electrophysiological assessment in patients with Mobius syndrome and clumsiness.
AB  - The authors studied the nature of clumsiness in Mobius syndrome in terms of motor
      or sensory deficits, and sought to clarify the pathophysiological mechanism of
      the syndrome. Standardized electrophysiologic studies were conducted, with
      special emphasis on the long motor and sensory tracts and peripheral nerves, in
      seven Mobius patients with clumsiness, of whom six participated in MRI studies;
      five of them showing brainstem hypoplasia. All performed motor-evoked potentials
      were normal. In all patients, normal somatosensory-evoked potentials were
      recorded and peripheral nerve conduction assessment revealed no abnormalities.
      The electrophysiologic data indicate that the traversing motor and sensory tracts
      through the brainstem, and the peripheral nerves are not affected in Mobius
      syndrome.

PMID- 16462201
TI  - Molecular neuropathology of epilepsy-associated glioneuronal malformations.
AB  - Glioneuronal malformations (malformations of cortical development [MCD]) include
      focal cortical dysplasias (FCD) as well as highly differentiated glioneuronal
      tumors (i.e. gangliogliomas) and constitute frequent findings in patients with
      pharmacoresistent focal epilepsies. Tailored resection strategies evolved as
      promising treatment options and allow a systematic neuropathologic and molecular
      biologic examination of the epileptogenic area in these patients. The
      histopathologic appearance and immunophenotype of glioneuronal lesions are,
      however, characterized by numerous similarities and suggest impaired
      proliferation, migration, and differentiation of neural precursor cells to play a
      pathogenetic role. Recent studies point toward molecular alterations within a
      variety of genes and pathways involved in development of the central nervous
      system, neuronal growth, and maturation. Compromised signaling within insulin- or
      reelin-transduction cascades are common findings and were associated with
      specific MCD entities. Unraveling pathogenic mechanisms may advance refined
      classification systems for epilepsy-associated malformations and open new avenues
      for the development of targeted treatment strategies in pharmacoresistent focal
      epilepsies associated with cortical malformations.

PMID- 16462202
TI  - High plasma cyst(e)ine level may indicate poor clinical outcome in patients with
      acute stroke: possible involvement of hydrogen sulfide.
AB  - Cysteine is known to cause neuronal cell death and has been reported to be
      elevated in brain ischemia, but it has not been studied in clinical stroke. In
      this study, we correlated plasma levels of cyst(e)ine with long-term clinical
      outcome at 3 months in acute stroke. Patients were classified into 3 groups at 3
      months as follows: good outcome (Rankin 0-1, n = 11), poor outcome (Rankin 2-5, n
      = 20), and dead (n = 5). Their plasma cyst(e)ine levels within 24 hours of stroke
      onset were 61 +/- 12, 67 +/- 9, and 82 +/- 14 micromol/L (standard deviation),
      respectively. The correlation between early plasma cyst(e)ine levels and long
      term clinical outcome assessed at 3 months is significant with p < 0.001. None of
      the other 4 amino acids studied showed any significant correlation. Cyst(e)ine
      was also significantly elevated in patients who had early stroke deterioration (p
      < 0.02). Dose-dependent administration of cysteine increased the infarct volume
      by approximately 30% in a rat stroke model. This effect of cysteine was abolished
      by aminooxyacetic acid, an inhibitor of the enzyme cystathionine beta-synthase
      that converts cysteine to hydrogen sulfide (H2S), indicating that this novel
      neuromodulator may be acting as a mediator of ischemic brain damage. Raised
      plasma cyst(e)ine in patients with stroke may reflect increased production of H2S
      in the brain and thus predispose to poor outcome in clinical stroke. Inhibition
      of H2S formation may therefore be a novel approach in acute stroke therapy.

PMID- 16462203
TI  - Relationship of apolipoprotein E and age at onset to Parkinson disease
      neuropathology.
AB  - Previous studies investigating the association between apolipoprotein E (APOE)
      genotypes and Parkinson disease (PD) have yielded conflicting results, and only a
      few have addressed APOE as a possible determinant of PD pathology. Therefore, we
      aimed to evaluate the relationship between APOE and PD as well as APOE and PD
      pathology. We studied 108 pathologically verified patients with PD and 108
      controls pair-matched for age and gender. Allele frequencies of APOE differed
      between patients with PD and controls (p = 0.02). The frequency of epsilon4
      allele increased (p = 0.01), whereas that of epsilon3 allele decreased with
      advancing PD pathology (p = 0.002). Only age of PD onset was an independent
      predictor for the rate of progression of PD pathology in which late-onset
      patients appeared to reach end point PD pathology more rapidly than early-onset
      patients (p = 0.001). In conclusion, our findings suggest that APOE may express
      its effect on the risk of PD by modifying the occurrence of PD pathology, but age
      of PD onset seems to be the principal determinant of the progression rate of PD
      pathology.

PMID- 16462204
TI  - Dendritic cells in multiple sclerosis lesions: maturation stage, myelin uptake,
      and interaction with proliferating T cells.
AB  - In multiple sclerosis (MS), dendritic cells (DCs) recruited to the central
      nervous system (CNS) are thought to be involved in the regulation of autoimmune
      responses directed against myelin antigens. To better understand the role of DCs
      in CNS inflammation, we performed a detailed immunohistochemical analysis of DC
      maturation markers and of DC relationship to CNS-infiltrating T cells in autopsy
      brain tissue of patients with MS. We also investigated the presence of DCs
      containing myelin debris in MS lesions. Myeloid DC subsets were identified using
      the following markers: CD1a for immature DCs; DC-SIGN for immature and mature
      DCs; and fascin, CD83, DC-LAMP, and CCR7 for mature DCs. The most common finding
      was the presence of cells expressing DC-SIGN and containing myelin components in
      the perivascular cuffs of early active and chronic (both active and inactive) MS
      lesions. Perivascular CD1a DCs were detected in active lesions in only one of 10
      patients with MS who were examined. Although less numerous than DC-SIGN DCs,
      cells expressing mature DC markers were consistently detected in the inflamed
      meninges and perivascular cuffs of most active lesions examined. CCR7
      immunostaining was predominantly confined to activated microglia at the lesion
      edges. Some perivascular DC-SIGN cells were found in close proximity to or
      contacting rare proliferating lymphocytes, most of which expressed the DC-SIGN
      ligand ICAM-3 and CD8. These data suggest that DCs recruited and maturing in MS
      lesions, where self-antigens are made available by continuous myelin destruction,
      may contribute to the local activation and expansion of presumably pathogenic T
      cells.

PMID- 16462205
TI  - Astroglial activation of extracellular-regulated kinase in early stages of
      Alzheimer disease.
AB  - Characterization of the earliest neuropathologic features of Alzheimer disease
      (AD) indicates that synaptic degeneration accompanied by tau hyperphosphorylation
      and amyloid deposition might be an important feature. The mechanisms involved are
      unclear; however, dysregulation of signaling cascades such as the extracellular
      signal-regulated kinase (ERK) pathway might play a role. In this context, the
      main objective of this study was to determine whether ERK hyperactivation occurs
      in early stages of AD. We compared the patterns of total and phosphorylated ERK
      (pERK) expression in the midfrontal cortex of patients clinically and
      neuropathologically characterized with early, intermediate, or advanced AD.
      Immunocytochemical and Western blot analysis showed that in early AD, there was
      extensive activation of ERK in astroglial cells in the white matter accompanied
      by intense astrogliosis. In contrast, in patients with more advanced AD, pERK
      immunoreactivity was associated with neuronal cell bodies and dystrophic neurites
      around plaques. Levels of astroglial pERK immunoreactivity in the white matter
      were strongly correlated with scores of cognitive performance (Blessed, Mini
      Mental Status Examination, and Clinical Dementia Rating) and with the severity of
      AD neuropathology (Braak stage). These findings suggest that astroglial ERK
      activation may be an important early response to the onset of AD pathology.
      Identification of cell signaling events unique to early AD may provide
      therapeutic targets for the prevention or delay of dementia.

PMID- 16462206
TI  - TRAIL-induced apoptosis in U-1242 MG glioma cells.
AB  - Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis
      in U-1242 MG cells. To investigate the molecular events involved in this process,
      we studied the effects of TRAIL on the localization within membrane fractions of
      molecules critical to the extrinsic apoptotic pathway. We report here that death
      receptor-5 (DR5), tumor necrosis factor receptor-1 (TNF-R1), and Fas receptor
      (FasR) are all located in the caveolin-1-enriched membrane fractions, and TRAIL
      caused the translocation of DR5, FasR, and TNF-R1 to the caveolar fractions.
      Caspase-8 is mainly located outside of caveolae, but TRAIL caused it to
      redistribute to the caveolin-1-enriched fractions where it was cleaved. Within 6
      hours, the cleaved caspase-8 appeared in the high-density, noncaveolin fractions.
      Using confocal microscopy, we found that DR5, caspase-8, and caveolin-1 became
      progressively concentrated in blebs of plasmalemma as they formed in response to
      TRAIL. Our results provide the first evidence for the caveolar localization of
      TNF-R1 and DR5 and the coordinated redistribution among membrane fractions of
      several death receptors in response to TRAIL. We propose that the coordinated
      movement of these molecules among membrane compartments is probably an important
      component of the mechanisms regulating and initiating the extrinsic apoptotic
      pathway in human glioma cells.

PMID- 16462207
TI  - Neuregulin growth factors and their ErbB receptors form a potential signaling
      network for schwannoma tumorigenesis.
AB  - Sporadic and neurofibromatosis type 2-associated schwannomas contain a glial
      growth factor (GGF)-like activity that has been hypothesized to promote
      neoplastic Schwann cell mitogenesis. It is not known whether this GGF-like
      activity is neuregulin-1 (NRG-1), an epidermal growth factor (EGF)-related
      molecule that regulates the proliferation, survival, and differentiation of
      developing Schwann cells, the related factor NRG-2, or another NRG/EGF ligand. We
      report that neoplastic Schwann cells within schwannomas overexpress multiple
      alpha and beta transmembrane precursors from the class II and class III NRG-1
      subfamilies. NRG-2 alpha and beta transcripts are similarly overexpressed in some
      tumors. Of the other 8 known NRG/EGF ligands, only heparin-binding EGF,
      epiregulin, and TGFalpha are detectable in schwannomas. Neoplastic Schwann cells
      almost uniformly express erbB2 and erbB3, 2 membrane receptor tyrosine kinases
      mediating NRG-1 and NRG-2 action. Expression of the NRG receptor erbB4 and EGF
      receptor is also evident in schwannomas, but is more limited, occurring in only a
      subset of these tumors. ErbB2, the preferred dimerization partner for all erbB
      kinases, is constitutively phosphorylated in schwannomas. These observations
      suggest that autocrine, paracrine, and/or juxtacrine NRG-1/NRG-2 signaling
      promotes schwannoma pathogenesis and that this signaling pathway may be an
      important therapeutic target in schwannomas.

PMID- 16462209
TI  - Neuro-muscular biopsy in Churg-Strauss syndrome: 24 cases.
AB  - Churg-Strauss syndrome (CSS) is a distinctive clinical entity in which systemic
      vasculitis, associated with eosinophilia, occurs almost exclusively in
      individuals with adult-onset asthma. The major complications of the condition
      result from damage to the lungs, heart, and peripheral nerves. Necrotizing
      vasculitis with eosinophils in the cellular infiltrate, vascular or perivascular
      infiltration by eosinophils in absence of vessel wall necrosis, extra-vascular
      eosinophil infiltrates, and vascular or extra-vascular granuloma are
      histopathological features supportive of CSS. As the peripheral nerve disease
      often dominates the clinical picture, the peripheral nerve biopsy may be decisive
      in establishing the diagnosis. In this retrospective study of neuro-muscular
      biopsies in 24 CSS cases, the authors give an extensive description of
      neuropathological lesions associated with this disorder. Fifteen patients (62.5%)
      exhibited eosinophils either in extra-vascular infiltrates or in vessel walls,
      and 6 of them (25%) had an associated necrotizing vasculitis. Granulomas were
      found in only 3 cases (12.5%). The clinical diagnosis of CSS was supported in 15
      out of the 24 patients (62.5%), in the nerve in 2 cases (8.3%), in the muscle in
      8 cases (33.3%), and in both nerve and muscle in 5 others (20.8%).

PMID- 16462208
TI  - OTX1 and OTX2 expression correlates with the clinicopathologic classification of
      medulloblastomas.
AB  - OTX1 and OTX2 are transcription factors with an essential role in the development
      of the cerebellum. We previously described a high OTX2 expression in
      medulloblastoma. Here, we analyzed amplification and mRNA expression of OTX1 and
      OTX2 in a series of human medulloblastomas. In addition, OTX2 protein expression
      was analyzed on tissue arrays. The OTX2 gene was amplified in the medulloblastoma
      cell line D425 and mRNA and protein data showed expression in 114 of 152
      medulloblastomas (75%), but not in postnatal cerebellum. Northern blot (n = 10)
      and reverse transcriptase-polymerase chain reaction (n = 45) analyses
      demonstrated that virtually all medulloblastomas expressed OTX1, OTX2, or both.
      OTX2 mRNA expression correlated with a classic medulloblastoma histology (29 of
      34 cases), whereas expression of OTX1 mRNA only was correlated with a
      nodular/desmoplastic histology (9 of 11 cases). Immunohistochemical analysis of a
      series of classic medulloblastomas detected OTX2 protein expression in 83 of 107
      (78%) cases. The OTX2-positive tumors of this series were preferentially
      localized in the vermis of the cerebellum, whereas OTX2-negative tumors more
      frequently occurred in the hemispheres of the cerebellum. In addition, OTX2
      positive tumors were mainly found in children, but OTX2-negative tumors occurred
      in 2 patient groups: very young patients (<5 years) and adults (>20 years).
      Nodular/desmoplastic medulloblastomas are thought to arise from the external
      granular layer (EGL). However, it is unclear whether classic medulloblastomas
      also originate from the EGL or from the ventricular matrix. Analysis of human
      fetal brain showed OTX2 protein expression in a small number of presumptive
      neuronal precursor cells of the EGL, but not in precursor cells of the
      ventricular matrix. Combined with data from rodents, our results therefore
      suggest that both nodular/desmoplastic and at least part of the classic
      medulloblastomas originate from cells of the EGL, albeit from different regions.

PMID- 16462210
TI  - Brain oxidative stress induced by obstructive jaundice in rats.
AB  - The effect of experimental obstructive jaundice on the oxidative status of brain
      tissues in rats was examined. Twenty-four male Wistar rats were divided into 4
      groups: Group I was the control, group II was the sham operated, and groups III
      and IV were bile duct ligated and killed on the 5th and the 10th day,
      respectively. Oxidative stress was assessed by measuring the thiol redox state
      (protein and nonprotein components) and lipid peroxidation level variations in
      samples from the cerebral cortex, midbrain, and cerebellar tissue in all animals.
      Results indicated the presence of oxidative stress in the jaundiced animals that
      was more pronounced on the 10th day as indicated by a decrease in reduced
      glutathione and protein thiol and an increase in protein disulphide and lipid
      peroxidation. A dramatic elevation of the level of total nonprotein mixed
      disulphide level was found specifically in the midbrain in the 10th day group.
      This suggests an accumulation of nonprotein disulfides other than oxidized
      glutathione, which remained unchanged, in this particular brain area. This study
      showed a correlation between experimental obstructive jaundice and the oxidative
      stress in the rats' brain, implying that a similar pathogenetic mechanism may
      play a key role in cholestatic liver disease, resulting in hepatic encephalopathy
      in humans.

PMID- 16462211
TI  - Surgical decision making for unstable thoracolumbar spine injuries: results of a
      consensus panel review by the Spine Trauma Study Group.
AB  - OBJECTIVES: The optimal surgical approach and treatment of unstable thoracolumbar
      spine injuries are poorly defined owing to a lack of widely accepted level I
      clinical literature. This lack of evidence-based standards has led to varied
      practice patterns based on individual surgeon preferences. The purpose of this
      study was to survey the leaders in the field of spine trauma to define the major
      characteristics of thoracolumbar injuries that influence their surgical decision
      making. In the absence of good scientific data, expert consensus opinions may
      provide surgeons with a practical framework to guide therapy and to conduct
      future research. METHODS: A panel of 22 leading spinal surgeons from 20 level I
      trauma centers in seven countries met to discuss the indications for surgical
      approach selection in unstable thoracolumbar injuries. Injuries were presented to
      the surgeons in a case scenario survey format. Preferred surgical approaches to
      the clinical scenarios were tabulated and comments weighed. RESULTS: All members
      of the panel agreed that three independent characteristics of thoracolumbar
      injuries carry primary importance in surgical decision making: the injury
      morphology, the neurologic status of the patient, and the integrity of the
      posterior ligaments. Six clinical scenarios based on the neurologic status of the
      patient (intact, incomplete, or complete) and on the status of the posterior
      ligamentous complex (intact or disrupted) were created, and consensus treatment
      approaches were described. Additional circumstances capable of altering the
      treatments were acknowledged. CONCLUSIONS: Decision making for the surgical
      treatment of thoracolumbar injuries is largely dependent on three patient
      characteristics: injury morphology, neurologic status, and posterior ligament
      integrity. A logical and practical decision-making process based on these
      characteristics may guide treatment even for the most complicated fracture
      patterns.

PMID- 16462212
TI  - Clinical study of a modified Brooks technique for atlanto-axial subluxation using
      polyethylene tape.
AB  - Forty-four patients, 15 males and 29 females (3-71 years old; mean age, 52.9),
      were treated for the control of cervical instability with a modified Brooks
      operation using Tekmilon tape (an ultrahigh molecular weight polyethylene tape)
      instead of metal wires. Forty of the patients had rheumatoid arthritis (RA) with
      atlanto-axial subluxation (AAS), three patients had os odontoideum, and one
      patient had a cervical spine injury. The mean follow-up period was 8 years and 4
      months. These patients were divided into three groups: 30 years or less, 31 to 60
      years, and over 60 years. Atlanto-dental interval (ADI), inclination angle of
      atlanto-axial vertebrae (A-A angle), and bone fusion were examined on plain
      radiographs. The proportion of patients with reduced neck pain (Ranawat's grade 0
      or grade 1) increased from 42.5% to 97.9% at the time of postoperative
      evaluation. Surgical complications, such as dural tear, lamina fracture, and
      spinal cord injury did not occur in any cases. Thirty-nine patients (88.6%)
      achieved bone union. ADI in the maximum flexed position improved from 10.3 to 2.5
      mm. There was no statistical difference between ADI in males and females. ADI did
      not change in any age group both before and after surgery. A-A angle also
      improved from 9.4 to 24.4 degrees. The polyethylene tapes, used for internal
      fixation, caused no neurologic complications during sublaminar wiring and
      produced no MR artifacts. This modified Brooks technique using Tekmilon tape was
      proved to be a simple and safe treatment of AAS.

PMID- 16462213
TI  - Use of spinous processes to determine drill trajectory during placement of
      lateral mass screws: a cadaveric analysis.
AB  - OBJECTIVE: Prior cadaveric research showed that the lateral mass and facets are
      landmarks to determine the initial starting point for lateral mass screws and
      that the optimum screw trajectory was 30 degrees lateral and 15 degrees cephalad.
      The missing link was an intraoperative landmark to guide the trajectory for
      drilling according to these angles. The authors hypothesized that spinous
      processes can be used to guide the trajectory for lateral mass screw placement.
      METHODS: The authors analyzed 144 lateral masses of 72 cervical vertebrae in 18
      cadavers (7 males and 11 females). The lateral and cephalocaudad angles were
      measured for each lateral mass from C3 to C6 while using the spinous processes of
      the adjacent three caudad vertebrae at each level to guide the starting
      trajectories for a total of 864 angles. The lateral and cephalad trajectory
      angles at each spinous process relative to the starting hole were compared with
      30 degrees and 15 degrees . For each angle measured at a particular level, the
      same starting hole was used in the lateral mass, and the superolateral cortex of
      each spinous process was the most medial point. RESULTS: When drilling for the C3
      and C4 lateral mass screws, the C4 and C5 spinous processes provided an accurate
      starting point, respectively, for the lateral angle but moderately overestimated
      the cephalocaudad angle. For C5 and C6 lateral mass screws, the C6 and C7 spinous
      processes provided an accurate starting point, respectively, for both the lateral
      and the cephalocaudad angles. CONCLUSION: The spinous processes can be an
      accurate local anatomic guide for lateral mass screw trajectory and will allow
      greater safety while drilling before performing laminectomies. These guides may
      change in patients with cervical spinal deformities.

PMID- 16462214
TI  - The use of computerized image guidance in lumbar disk arthroplasty.
AB  - OBJECTIVES: Surgical navigation systems have been increasingly studied and
      applied in the application of spinal instrumentation. Successful disk
      arthroplasty requires accurate midline and rotational positioning for optimal
      function and longevity. A surgical simulation study in human cadaver specimens
      was done to evaluate and compare the accuracy of standard fluoroscopy, computer
      assisted fluoroscopic image guidance, and Iso-C3D image guidance in the placement
      of lumbar intervertebral disk replacements. METHODS: Lumbar intervertebral disk
      prostheses were placed using three different image guidance techniques in three
      human cadaver spine specimens at multiple levels. Postinstrumentation accuracy
      was assessed with thin-cut computed tomography scans. RESULTS: Intervertebral
      disk replacements placed using the StealthStation with Iso-C3D were more
      accurately centered than those placed using the StealthStation with FluoroNav and
      standard fluoroscopy. Intervertebral disk replacements placed with Iso-C3D and
      FluoroNav had improved rotational divergence compared with standard fluoroscopy.
      Iso-C3D and FluoroNav had a smaller interprocedure variance than standard
      fluoroscopy. These results did not approach statistical significance. Relative to
      both virtual and standard fluoroscopy, use of the StealthStation with Iso-C3D
      resulted in improved accuracy in centering the lumbar disk prosthesis in the
      coronal midline. CONCLUSIONS: The StealthStation with FluoroNav appears to be at
      least equivalent to standard fluoroscopy and may offer improved accuracy with
      rotational alignment while minimizing radiation exposure to the surgeon. Surgical
      guidance systems may offer improved accuracy and less interprocedure variation in
      the placement of intervertebral disk replacements than standard fluoroscopy.
      Further study regarding surgical navigation systems for intervertebral disk
      replacement is warranted.

PMID- 16462215
TI  - Efficacy of pneumatic compression stocking prophylaxis in the prevention of deep
      venous thrombosis and pulmonary embolism following 139 lumbar laminectomies with
      instrumented fusions.
AB  - OBJECTIVE: Low-dose heparin (LDH) regimens reduce the frequency of deep venous
      thrombosis (DVT) and pulmonary embolism (PE) in spinal surgery but pose a risk of
      postoperative hemorrhage threatening neurologic function. Pneumatic compression
      stocking (CS) could provide an alternative means of mechanical prophylaxis alone
      against DVT and PE and would possibly avoid its hemorrhagic complications.
      METHODS: The efficacy of CS alone in preventing DVT and PE was evaluated in 139
      patients undergoing multilevel lumbar laminectomies (average 3.8 levels) with
      instrumented fusions (average 1.4 levels). All patients received CS stocking
      prophylaxis intraoperatively and throughout the average 5-day postoperative
      course including following ambulation. Doppler screening for DVT was routinely
      performed 2 days postoperatively. Subsequent Doppler studies or computed
      tomography angiograms were selectively performed in symptomatic patients with
      potential DVT/PE. RESULTS: Four (2.8%) patients developed DVT 2-6 days
      postoperatively and required inferior vena cava (IVC) filters. One of the four
      had a positive routine screening Doppler study performed the second postoperative
      day. Two developed DVT the fourth postoperative day. The fourth patient developed
      DVT 6 days postoperatively but 3 weeks later embolized around the IVC filter.
      This patient, the only one to develop a PE, tested positive for Factor V Leiden
      mutation (hypercoagulable syndrome) and remains on long-term warfarin.
      CONCLUSIONS: Pneumatic compression stocking prophylaxis effectively reduced the
      incidence of DVT (2.8%) and PE (0.7%) in 139 patients undergoing multilevel
      lumbar laminectomies with instrumented fusions. These rates compared favorably
      with those reported in spinal series employing LDH prophylaxis.

PMID- 16462216
TI  - In vitro study of shear force on interbody implants.
AB  - OBJECTIVE: The lordosis of the lumbar spine and body weight result in significant
      shear forces through the lumbosacral disc spaces. These forces result in
      translational motion across the disc space, which is resisted but not completely
      abolished by pedicle screw stabilization. It is postulated that this motion may
      be a factor in the development of nonunion of lumbar interbody fusions. An in
      vitro study of the micromotion of porcine specimens implanted with serrated or
      smooth interbody spacers and subjected to shear forces under compressive preload
      was conducted to determine whether the surface serrations on vertebral interbody
      implants significantly resist shear forces and resulting sagittal translation.
      METHODS: Measurements of anterior vertebral translation were recorded on porcine
      cervical spine segments, subjected to 25 N of anteroposterior shear load while
      under a 300-N compressive preload. Baseline testing was performed on intact
      specimens and partially destabilized specimens (facet joints removed). Following
      partial discectomy, the specimens were divided into two groups for testing: one
      using smooth-surfaced and one using serrated interbody spacers. RESULTS: Under 25
      N shear load, the specimens tested with the serrated spacers showed anterior
      vertebral translation of 0.046 +/- 0.013 mm, whereas those tested with the smooth
      spacers measured 0.152 +/- 0.075 mm (P < 0.01). CONCLUSIONS: The presence of
      surface serrations on the interbody implants significantly increased the
      resistance to shear forces in this model. In the clinical setting, we postulate
      that micromotion at interbody fusion sites will be substantially less when
      serrated implants are used and may help reduce the incidence of nonunion.

PMID- 16462217
TI  - Continuous EMG recordings and intraoperative electrical stimulation for
      identification and protection of cervical nerve roots during foraminal tumor
      surgery.
AB  - OBJECTIVE: Spinal cord function is now routinely monitored with somatosensory
      evoked potentials (SEPs) and motor evoked potentials (MEPs) during surgery for
      intraspinal cervical dumbbell and foraminal tumors. However, upper extremity
      nerve roots are also at risk during these procedures. Anatomic relations are
      frequently difficult to interpret because the nerve roots may be displaced by the
      tumor. We used electrical stimulation with compound muscle action potential
      (CMAP) recordings at multiple sites to identify the location and course of the
      involved nerve root and to provide real-time information regarding the functional
      status of the roots to predict postoperative outcome. METHODS: Ten patients were
      monitored during surgery for cervical dumbbell or foraminal tumors. SEPs and MEPs
      were monitored as a routine procedure. CMAPs were recorded from needle electrodes
      placed in the deltoid, biceps, triceps, and flexor carpi ulnaris muscles.
      Spontaneous electromyography (EMG) muscle activity was also continuously
      monitored. A handheld monopolar stimulation electrode was used to elicit evoked
      EMG responses to identify and trace the course of nerves in relation to the
      tumor. In four patients, the stimulation threshold was tested before and after
      tumor resection to predict postoperative nerve root function. RESULTS: Electrical
      stimulation with CMAP recording was successful in localizing nerve roots during
      tumor resection in all 10 patients. Monitoring predicted postoperative nerve root
      preservation after tumor removal in each case. It was possible to identify either
      by using low-level stimulation (<2.0 V) or by observing changes in spontaneous
      EMG amplitude if activation was present during surgical dissection. The
      monitoring of spontaneous muscle activity in response to direct or indirect
      surgical manipulation during tumor resection also provided continuous assessment
      of nerve root function and identified any physiologic disturbance induced by
      surgical manipulation. CONCLUSIONS: Electrical stimulation in the operating field
      and recording of CMAPs facilitated nerve root identification and predicted
      postoperative function during dissection and separation from ligamentous or
      neoplastic tissue in 10 patients. Electrical stimulation might also be useful to
      predict postoperative preservation of function when nerve root sacrifice is
      necessary and no motor response is detected intraoperatively.

PMID- 16462218
TI  - Intramedullary spinal cord metastasis: a clinical and imaging study of seven
      patients.
AB  - OBJECTIVES: Intramedullary spinal cord metastasis (ISCM) is a rare complication
      of cancer. This complication has been studied by magnetic resonance imaging (MRI)
      more frequently in the clinical context to improve the survival time of cancer
      patients. However, the number of the reports of its clinical management or
      radiographic findings is small. To investigate the clinical and imaging
      characteristics of ISCM, seven cases of ISCM of a nonneurogenic origin were
      examined retrospectively. METHOD: Data regarding the site of the primary
      neoplasm, location of other metastases, initial symptoms, interval from the
      original diagnosis of cancer to the onset of neurologic symptoms, time course
      from initial symptoms to urinary retention, MRI data, and outcome after
      radiologic or surgical intervention were investigated. RESULTS: Five patients had
      lung cancer metastases, and one each had breast or uterine cancer metastases. The
      progression of neurologic deficit was rapid, and the average period between the
      occurrence of initial symptoms and urinary retention was 25 days. The averaged
      survival period from the diagnosis of ISCM was 5 months in three patients. (One
      patient is alive, and the data could not be obtained in another three patients.)
      MRI characteristics were useful for diagnosis, including large high signal
      intensity areas on T2-weighted images and strong ring or inhomogeneous
      enhancement on gadopentetate dimeglumine-enhanced T1-weighted images. Surgery was
      performed on two patients, but total removal could not be achieved. Radiotherapy
      was effective in treating neurologic deficit in five patients. CONCLUSION:
      Surgical treatment is seldom indicated for ISCM, and radiotherapy is recommended
      as soon as possible after a diagnosis is made from MRI.

PMID- 16462219
TI  - Delayed reconstruction by titanium mesh-bone graft composite in pyogenic spinal
      infection: a long-term follow-up study.
AB  - OBJECTIVE: Use of instrumentation in spinal osteomyelitis remains controversial
      because of the perceived risk of persistent infection related to a devitalized
      graft and spinal hardware. Particularly, limited information is available
      regarding the long-term follow-up of patients. We retrospectively reviewed the
      use of titanium mesh-bone graft composite after corpectomy in pyogenic spinal
      infection with a minimum 3-year follow-up outcome. METHODS: Four patients, two
      men and two women, with cervical and thoracic myelopathy caused by cervical (two
      cases) and thoracic (two cases) osteomyelitis and epidural abscess, were treated.
      Their age ranged from 49 to 74 years (mean age 58 years). In one case, the
      coexisting medical condition was diabetes. Neurologic deficits caused by direct
      spinal cord compression due to epidural abscess, segmental deformity, and
      instability were observed in all cases. After infection was clinically controlled
      by intravenous antibiotics, anterior debridement and fusion using titanium mesh
      cage along with anterior plate were performed. Two-stage treatment was performed
      in two cases. RESULTS: The postoperative course was uneventful; all patients
      experienced relief of symptoms. No evidence of recurrence or residual infection
      was observed in any patient during the average follow-up period of 42-56 months
      (average 49.0 months). CONCLUSIONS: Once infection is clinically controlled, a
      titanium mesh-bone graft composite and plate in combination with aggressive
      debridement might provide an effective therapy for spinal osteomyelitis requiring
      surgery. Despite studying a small number of patients, we can conclude that
      titanium mesh reconstruction can be useful as a surgical method in selected low
      risk patients with vertebral osteomyelitis.

PMID- 16462220
TI  - Early failure of lumbar disc replacement: case report and review of the
      literature.
AB  - We report a case of a patient who underwent two-level lumbar total disc
      replacement at L4-L5 and L5-S1 with the ProDisc II prosthesis, who was diagnosed
      with early anterior migration of the caudally placed device with partial
      occlusion of the left common iliac vein. The device was explanted and revised to
      an anterior lumbar interbody fusion with posterior instrumented fusion. Despite
      the substantial experience with lumbar disc arthroplasty in Europe and the United
      States, there exist few reports of device explantation or revision. To our
      knowledge, early postoperative vascular complications, while discussed
      hypothetically, have not been reported. With implantation of the total disc
      replacement in proximity to the great vessels, the potential for vascular
      complications is clearly substantial. The technical aspects of the device
      explantation are discussed as well as issues pertinent to early failure. A
      literature review of device complications associated with lumbar total disc
      replacement is also presented.

PMID- 16462221
TI  - The use of external fixation for the treatment of spine infection with
      Actinomyces bacillus.
AB  - OBJECTIVE: External fixation can be used for stabilization of the spine in
      salvage cases, especially in cases of infection of the spine. The advantages of
      this method are avoiding the needs for internal fixation devices and for
      postoperative bracing. The literature on this is scant. Reported is a rare case
      of osteomyelitis of the D2 vertebra with an epidural abscess caused by
      Actinomyces israelii that spread from the lung and was treated by decompression
      and external fixation. METHODS: A 51-year-old man with right upper lobe pneumonia
      due to A. israelii coccobacillus developed osteomyelitis of the D2 vertebra and
      an epidural abscess with a gradual paraparesis. He underwent a laminectomy of D1
      D3 and 3 weeks later stabilization of the upper thoracic spine using a tubular
      external fixator that was inserted from C7-D1 to D3-D4. The patient was treated
      with antibiotic intravenously and later orally. After 2 months, the external
      fixator was removed. RESULTS: At the last follow-up, the patient had no fever,
      the erythrocyte sedimentation rate and C-reactive protein level had normal
      values, and there was only a slight limitation in the range of motion of the
      cervical paraparesis. Radiography and magnetic resonance imaging demonstrated
      stabilization of the affected segment without any sign of active osteomyelitis.
      There were no complications associated with the use of the external fixator.
      CONCLUSIONS: The use of external fixation offers an appropriate alternative for
      stabilization of the spine as a salvage procedure. The procedure could be
      performed easily and without any major complications. Especially for the
      treatment of complicated cases of spinal infection, the use of an external
      fixator can be of great benefit.

PMID- 16462222
TI  - Unilateral spondylolysis combined with contralateral lumbar pediculolysis in a
      military parachutist.
AB  - A few cases of unilateral pediculolysis combined with contralateral spondylolysis
      have been reported, and most of them were related to athletic activities. A case
      of unilateral spondylolysis combined with contralateral lumbar pediculolysis in a
      military parachutist is reported. A 34-year-old man experienced low back pain and
      right sciatica for 3 months. Radiographs revealed a left spondylolysis combined
      with a right pediculolysis of the L5 vertebra. The patient had parachuted >300
      times in the last 5 years. Interbody fusion of L5-S1 was performed, and the
      patient was free of pain after surgery.

PMID- 16462224
TI  - Aneurysmal bone cyst of the second cervical vertebrae causing multilevel upper
      cervical instability.
AB  - OBJECTIVE: Aneurysmal bone cyst (ABC) is a rare expansile osteolytic lesion of
      bone comprising proliferating vascular tissue lining blood-filled cystic
      cavities. ABCs occur most frequently in patients under age 20 and are uncommon
      after 30 years of age. Three to 20% of cases occur in the spine, and upper
      cervical involvement is rare. Lesions may grow rapidly and attain considerable
      size. When involving the spine, ABCs may result in instability and neurologic
      compromise, making prompt diagnosis and treatment imperative. We present a report
      of a 6-year-old child with an ABC of the second cervical vertebrae causing
      atlantoaxial and C2-C3 instability, treated successfully with curettage,
      decompression, and anterior and posterior arthrodesis with posterior
      instrumentation. METHODS: The patient underwent a staged procedure consisting of
      posterior instrumentation from occiput to C4 and curettage of the lesion followed
      by anterior cervical discectomy and fusion of C2-C4. The diagnosis, surgical
      treatment, and outcome of the case are described and relevant literature
      reviewed. RESULTS: The patient sustained no lasting neurologic deficits and was
      disease-free at 3 years of follow-up. CONCLUSIONS: ABC is a rare but potentially
      devastating cause of upper cervical spine instability. Prompt detection and
      treatment with curettage, decompression, and fusion can produce a satisfactory
      result and prevent spinal cord injury.

PMID- 16462223
TI  - Thoracic paraparesis following an embolic vascular event during lumbar spinal
      surgery.
AB  - OBJECTIVE: A case report illustrating the rare occurrence of thoracic paraparesis
      following the presumed occurrence of an embolic vascular event during lumbar
      spinal surgery is presented. The goal is to investigate the potential causes of
      acute postoperative paraparesis following lumbar spine surgery. A discussion of
      the symptoms, diagnosis, differential diagnosis, and management of spinal cord
      ischemia and postembolic infarction is presented. This manuscript is intended to
      heighten the awareness of the potential for this rare complication to improve the
      speed and accuracy of diagnosis, allowing the timely institution of appropriate
      treatment. METHODS: Data analyzed include the patient history, preoperative and
      postoperative physical examination, clinical course, imaging studies, and input
      of various consulting services. A review of the English literature on spinal cord
      ischemia and postembolic infarction was performed. RESULTS: The most likely
      etiology for the patient's acute postoperative paraparesis appears to be related
      to an embolic spinal cord infarction. CONCLUSIONS: Management of a spinal cord
      ischemic event should focus on the following key issues: a prompt diagnosis with
      timely perioperative imaging studies (magnetic resonance imaging), the attainment
      of a normotensive state, the institution of systemic anticoagulation if
      clinically warranted, and maximization of physical function through early
      rehabilitation.

PMID- 16462233
TI  - When your patient develops phlebitis.

PMID- 16462234
TI  - Reaching and teaching older adults.

PMID- 16462240
TI  - Putting your life on the line.

PMID- 16462241
TI  - Documenting general observations.

PMID- 16462239
TI  - Hot topics in pain management: using NSAIDs safely.

PMID- 16462242
TI  - Improving the PICC insertion process.

PMID- 16462243
TI  - Assessing for hepatojugular reflux.

PMID- 16462244
TI  - Myths and facts...about primary hyperparathyroidism.

PMID- 16462249
TI  - How does oral emergency contraception work?

PMID- 16462258
TI  - Best-practice interventions: How can you prevent ventilator-associated pneumonia?

PMID- 16462261
TI  - Bewitched.

PMID- 16462262
TI  - Celiac disease goes against the grain.

PMID- 16462264
TI  - Make a point about alternate site blood glucose sampling.

PMID- 16462263
TI  - Taking the pressure off for women with stress incontinence.

PMID- 16462265
TI  - New drugs 06, part I.

PMID- 16462267
TI  - Viral meningitis in adults.

PMID- 16462277
TI  - Waking up to the benefits of safety I.V. catheters.

PMID- 16462281
TI  - E-mail: so fast, so convenient, so ... risky?

PMID- 16462279
TI  - Wound bed preparation: laying the foundation for treating chronic wounds, part I.

PMID- 16462282
TI  - Pericardial tamponade.

PMID- 16462284
TI  - Development of a practical tool for assessing the severity of acute otitis media.
AB  - BACKGROUND: Watchful waiting management of nonsevere acute otitis media (AOM) can
      reduce the use of antibiotics, but it requires a reliable means of assessing
      clinical severity. OBJECTIVE: We present the development of a pocket AOM card
      with which the clinician can rapidly assess total AOM severity. DESIGN/METHODS:
      The components of the pocket card consisted of a faces scale, to assess parent
      perception of severity, and a standard set of tympanic membrane photographs, with
      which the pediatrician can grade the severity of tympanic membrane inflammation.
      The components of the pocket card were tested for validity, reliability and
      responsiveness with the use of data from parents, pediatricians and pediatric
      otolaryngologists. STATISTICS: Instruments were assessed for concurrent
      correlation, sequence validity and reliability against previously published
      questionnaires with the use of Spearman correlation. Responsiveness was
      calculated with the use of enrollment, day 12 and day 30 data from a randomized
      clinical trial. RESULTS: The components of the pocket AOM card demonstrated
      excellent sequence validity, concurrent correlation and reliability (r = 0.58
      0.99). Total AOM card severity, consisting of the sum of the 2 scales,
      demonstrated better responsiveness to change than any of the scales taken
      individually. CONCLUSIONS: The AOM card combines a parent assessment of symptoms
      and the clinician assessment of the tympanic membrane to provide an assessment of
      total AOM severity that can be used to facilitate shared decision making between
      parent and clinician. The combined score of the AOM card was more responsive to
      change than any of the instruments used alone. The AOM card provides a useful
      tool for teaching and research.

PMID- 16462285
TI  - Nasal middle meatal specimen bacteriology as a predictor of the course of acute
      respiratory infection in children.
AB  - AIMS: To test our hypothesis that children with potentially pathogenic bacteria
      (Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis) in
      the nasal middle meatus might have more prolonged symptoms of acute respiratory
      infection than children without such bacteria, we conducted a prospective cohort
      study of such children. MATERIALS AND METHODS: We recruited prospectively child
      volunteers between 6 and 13 years of age with acute respiratory infections
      present for fewer than 10 days. Nasal middle meatal bacterial culture was taken
      with a rigid endoscope at enrollment and again after 3 weeks and evaluated for
      presence or absence of 3 potential pathogens: S. pneumoniae, H. influenzae and M.
      catarrhalis. The subsequent persistence of acute symptoms (nasal discharge:
      clear/colored, nasal obstruction and cough) was determined by means of a diary.
      Viral etiology was studied with polymerase chain reaction methods. RESULTS: The
      82 children had had symptoms for an average of 4 days (range, 1-10) at entry, and
      viruses were detected in 54% (39 of 72). The endoscopic procedure and
      bacteriologic sampling succeeded in all cases. Thirty-eight children (46%) had at
      least 1 of the 3 pathogens in the middle meatus specimen. The children with nasal
      pathogens present at entry had a significantly longer mean duration of symptoms
      than those with nonpathogenic bacteria (difference, 3.6 days; 95% confidence
      interval, 0.7-6.5; P = 0.025). The effect remained significant after adjustment
      for age, sex, allergic symptoms and the presence of virus (adjusted relative
      hazard of delayed recovery, 2.0; 95% confidence interval, 1.1-3.6). CONCLUSIONS:
      We found that the use of endoscopic swab culture sampling from the nasal middle
      meatus is well-tolerated by children older than 6 years of age and that it can be
      useful in selected situations to determine pathogenic bacteria in the culture of
      these specimens.

PMID- 16462287
TI  - Neonatal administration of rhesus rotavirus tetravalent vaccine.
AB  - BACKGROUND AND AIMS: Administration of the first dose of rhesus rotavirus-based
      tetravalent (RRV-TV) vaccine is followed by a transient febrile reaction at 3-4
      days postvaccination in about one-third of vaccinees. We hypothesized that giving
      the first dose of RRV-TV vaccine during the neonatal period might reduce the
      reactogenicity of RRV-TV vaccine without compromising the utilization of the
      vaccine. METHODS: A double blind placebo-controlled safety and immunogenicity
      trial of 90 infants who received RRV-TV vaccine at 0-4-6, 0-2-4 or 2-4-6 months
      of age was conducted. Reactions were evaluated for 1 week after each vaccination
      and, in addition, serum specimens were collected before vaccination and at 5 and
      7 months of age. RESULTS: Febrile reactions were not observed in 62 infants
      receiving the first dose of RRV-TV vaccine during the neonatal period. Five of
      the 28 (18%) infants receiving the first dose at 2 months were febrile on 1 or
      more days, whereas none of the 30 infants who had received a neonatal dose
      developed a fever when vaccinated again at 2 months of age. An enzyme-linked
      immunosorbent assay IgA antibody response after 3 doses was observed
      significantly less frequently (77%) in infants who had received a neonatal dose,
      a second dose at 2 months of age, and a third dose at 4 months of age compared
      with those who received their first dose at 2 months and a second dose at 4
      months (100%, P < 0.02). Also, the frequency of a neutralizing antibody response
      to RRV and human rotavirus serotypes G1-4 tended to be lower in the group that
      had received the vaccine at 0-2-4 months compared with those who received it at 2
      4-6 months. When the 2 tests were combined, the frequency of a seroresponse
      following the 0-2-4 month schedule (94%) was comparable with that following the 2
      4-6 month schedule (100%). CONCLUSION: Infants who received the first dose of RRV
      TV vaccine during the neonatal period did not develop a febrile reaction. The
      immune response in a 3-dose schedule initiated in the neonatal period is somewhat
      dampened but still acceptable. Neonatal immunization might also reduce the very
      small risk of intussusception, which has been associated with administration of
      RRV-TV vaccine to older infants.

PMID- 16462286
TI  - Risk factors for late onset gram-negative sepsis in low birth weight infants
      hospitalized in the neonatal intensive care unit.
AB  - BACKGROUND: Gram-negative bloodstream infections (BSIs) cause 20-30% of late
      onset sepsis in neonatal intensive care unit (NICU) patients and have mortality
      rates of 30-50%. We investigated risk factors for late onset Gram-negative sepsis
      in very low birth weight (<1500 g) NICU patients. METHODS: We performed a case
      control study as part of a larger 2-year clinical trial that examined the effects
      of hand hygiene practices on hospital-acquired infections. In this substudy, a
      case was a very low birth weight infant with a hospital-acquired Gram-negative
      BSI; control subjects, matched on study site and hand hygiene product, were
      chosen randomly from the patients who did not have Gram-negative BSIs. Potential
      risk factors were analyzed by Mantel-Haenszel methods and conditional logistic
      regression. RESULTS: There were 48 cases of Gram-negative BSI. In multivariate
      analysis, we found that the following variables were significantly associated
      with Gram-negative BSI: central venous catheterization duration of >10 days;
      nasal cannula continuous positive airway pressure use; H2 blocker/proton pump
      inhibitor use; and gastrointestinal tract pathology. CONCLUSIONS: These analyses
      provide insights into potential strategies to reduce Gram-negative BSIs.
      Catheters should be removed as possible and H2 blockers/proton pump inhibitors
      should be used judiciously in NICU patients. The association between nasal
      cannula continuous positive airway pressure and Gram-negative BSIs requires
      further investigation. The association of gastrointestinal tract pathology with
      Gram-negative BSIs identifies a high risk group of neonates who may benefit from
      enhanced preventative strategies.

PMID- 16462289
TI  - Population-based incidence of infection with selected bacterial enteric pathogens
      in children younger than five years of age, 1996-1998.
AB  - BACKGROUND: Previous studies of bacterial enteric infections have suggested a
      disproportionate disease burden for children younger than 5 years of age.
      OBJECTIVES: This study describes population-based incidence of culture-confirmed
      infections with 6 bacterial enteric pathogens in children younger than 5 years of
      age in the Foodborne Diseases Active Surveillance Network (FoodNet), 1996-1998.
      METHODS: Cases were ascertained through active laboratory-based surveillance in
      Minnesota, Oregon and selected counties in California, Connecticut, Georgia,
      Maryland and New York. RESULTS: Twenty-one percent (5218 of 24,358) of infections
      were in children younger than 5 years of age, but this age group made up only 7%
      of the total person-years of observation. Among those younger than 5 years of
      age, the incidence (cases per 100,000 person-years) for each pathogen was:
      Salmonella, 55.3; Campylobacter, 43.4; Shigella, 32.7; E. coli O157, 10.3;
      Yersinia enterocolitica, 7.1; Listeria monocytogenes, 0.7. Incidence varied
      widely among the 7 FoodNet sites. CONCLUSIONS: This study confirmed a
      disproportionate disease burden in young children. Investigation of risk factors
      specific to this age group and review and enhancement of current prevention and
      control strategies for children younger than 5 years of age may reduce illness.

PMID- 16462288
TI  - Cord blood screening for congenital toxoplasmosis in northwestern Switzerland,
      1982-1999.
AB  - BACKGROUND: In the absence of mandatory nationwide toxoplasmosis screening during
      pregnancy in Switzerland, the Basel region introduced cord blood screening in
      1982. METHODS: From 1982 to 1999, 64,622 cord blood samples (>90% of all
      neonates) collected in Basel region obstetric units were screened for toxoplasma
      specific immunoglobulin (Ig) G, M and A antibodies using commercial kits.
      Neonates with relevant results (IgG titers > or =300 IU/mL, or > or =200 IU/mL in
      the Abbott Toxo IMX system, and/or positive IgM or IgA antibodies) were monitored
      until clarification of infection status. From 1991 onward, retrospective maternal
      and follow-up data on these children were also collected by questionnaire.
      RESULTS: Despite increasing maternal age, seroprevalence for toxoplasmosis
      decreased steadily from 53% (1982-1985) to 35% (1999). During the same period,
      the prevalence of congenital toxoplasmosis declined from 0.08% to 0.012%. IgM
      and/or IgA antibodies were present with the Platelia Toxo test (enzyme-linked
      immunosorbent assay; sanofi pasteur; Bio-Rad) in the cord blood samples of 17 of
      18 infected neonates born between 1986 and 1999, regardless of maternal treatment
      in pregnancy. Vertical transmission rates in 69 women with proven or suspected
      primary infection between 1991 and 1999 were 3.9% with, compared to 27.7%
      without, antiparasitic treatment during pregnancy. CONCLUSION: Toxoplasma
      seroprevalence and congenital toxoplasmosis incidence declined markedly in
      northwestern Switzerland from 1982 to 1999. Our data provide no conclusive
      evidence that maternal antiparasitic therapy in pregnancy affects vertical
      transmission because the treatment group also included women with suspected but
      unproven primary infection during pregnancy. Because toxoplasma specific IgA/IgM
      antibodies in cord blood identified almost all infected children, screening at
      birth may be more cost effective than during pregnancy.

PMID- 16462290
TI  - Virologic and host characteristics of human immunodeficiency virus type 1
      infected pediatric long term survivors.
AB  - BACKGROUND: There are limited data concerning determinants of varying clinical
      progression rates in human immunodeficiency virus type 1 (HIV-1)-infected
      children. Therefore, we sought to determine whether viral or host factors
      associated with nonprogressive HIV-1 infection in adults play a role in limiting
      progression of infection in 5 vertically infected youths, ages 12-18 years, who
      have displayed no signs of advanced HIV-1 disease or acquired immunodeficiency
      syndrome despite having received minimal treatment with antiretroviral drugs.
      RESULTS: The 5 individuals, whom we characterize as long term survivors, have
      maintained low loads of HIV-1 RNA in plasma when compared to many of their peers,
      and have also maintained normal and stable CD4 T-lymphocyte numbers and
      percentages throughout their lives. Determination of their predominant HIV-1
      sequences revealed that 4 of 5 patients harbor virus with markers of resistance
      to their therapy (one was never treated). Furthermore 2 harbored viral isolates
      that contained insertions in Gag or Vif that inhibit HIV-1 replication. Moreover,
      2 were found to be heterozygous for the CCR2 polymorphism 64I, a genotype
      associated with slower progression to acquired immunodeficiency syndrome in
      adults. All 5 expressed the histocompatibility leukocyte antigen DQ1 and 2 had
      unusual DR/DQ1 phenotypes. CONCLUSIONS: We believe that the limited
      antiretroviral therapy received by the long term survivors cannot solely account
      for their benign clinical status. Therefore, we conclude that other factors,
      including gene polymorphisms that affect viral replicative capacity, account for
      the long term survival in some, and deduce that, as in adults, no single factor
      (virologic or host) can account for this clinical phenotype in all cases.

PMID- 16462291
TI  - Tuberculous lymphadenitis as a cause of persistent cervical lymphadenopathy in
      children from a tuberculosis-endemic area.
AB  - BACKGROUND: Cervical lymphadenitis is the most common form of extrapulmonary
      tuberculosis in children, although its relative contribution as a cause of
      persistent cervical adenopathy is not well-documented. The aim of this study was
      to determine the relative contribution of tuberculous lymphadenitis as a cause of
      persistent cervical adenopathy in a tuberculosis-endemic setting and to document
      its clinical presentation at the primary health care level. METHODS: A
      prospective descriptive study was conducted from February 2003 through October
      200 at 5 primary health care clinics in Cape Town, South Africa. The study
      included all children younger than 13 years presenting with persistent cervical
      adenopathy to the local primary health care clinic. RESULTS: A total of 158
      children were evaluated of whom 35 (22.2%) were diagnosed with tuberculous
      lymphadenitis. Bacteriologic confirmation was achieved in 27 of 35 (77.1%)
      children; all 35 responded to standard antituberculosis treatment. The majority
      of those without tuberculous lymphadenitis (105 of 123, 85.4%) had a visible
      superficial lesion in the area drained by the affected nodes. In children with
      persistent lymphadenopathy > or =2 x 2 cm, tuberculosis lymphadenitis was
      diagnosed in 31 of 33 (93.9%); specificity was 98.4%, sensitivity was 88.6% and
      the positive predictive value was 93.4%. CONCLUSION: Children commonly present
      with persistent cervical adenopathy to the primary health care clinic. The use of
      a simple clinical algorithm provided an accurate diagnosis of tuberculous
      lymphadenitis in the study setting. Fine needle aspirations provided a rapid and
      definitive diagnosis in the majority of children and will have added diagnostic
      value in settings where alternative diagnoses are more likely.

PMID- 16462292
TI  - Multidrug-resistant tuberculous meningitis in children in Durban, South Africa.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is the most frequent manifestation of
      central nervous system tuberculosis (TB) and is more common in children than in
      adults. The diagnosis of TBM in children is difficult because signs and symptoms
      are vague. Information about drug resistant TB in children is scarce, and there
      is no published information on drug resistant TBM in children. METHODS: This is a
      retrospective review of medical records of children with culture-confirmed
      multidrug-resistant tuberculous meningitis (MDR-TBM) at King George V Hospital in
      Durban, South Africa. RESULTS: Between 1992 and 2003, there were 8 children with
      MDR-TBM; 6 were HIV infected and 2 were HIV negative. Only one child survived.
      The diagnosis was made posthumously in almost all the children. DISCUSSION: The
      changes in the cerebrospinal fluid (CSF) in early TBM can be nonspecific and can
      change rapidly; therefore, CSF studies should always include culture and
      susceptibility testing. Factors that contributed to the high mortality were
      disseminated TB, HIV infection, delay in diagnosis and treatment, the absence of
      a standardized approach to the management of MDR-TBM and the poor CSF penetration
      of most MDR-TB drugs. MDR-TB therapy should be considered if there is a history
      of TB: a MDR-TB contact or a poor clinical response to TB therapy despite
      adequate adherence to treatment. Early diagnosis is important because TBM in
      children is often associated with a grave outcome.

PMID- 16462293
TI  - Increased reported cases of tuberculosis among children younger than 5 years of
      age, Maricopa County, Arizona, 2002-2003.
AB  - OBJECTIVES: Although tuberculosis (TB) rates in the United States among children
      younger than 5 years old (2.8/100,000 in 2003) have been declining, Maricopa
      County, Arizona, reported an increase from 4.1/100,000 in 2002 to 9.0/100,000 in
      2003. We investigated factors associated with this increase. METHODS: We reviewed
      county TB clinic records of pediatric patients (younger than 5 years old) and
      their probable adult sources, interviewed parents or guardians of pediatric TB
      patients and examined changes in clinic procedures. RESULTS: We verified 11
      pediatric TB cases in 2002 and 25 in 2003 (n = 36). A total of 31 (86%) patients
      were born in the United States, and 28 (78%) had at least 1 foreign-born parent.
      There were 19 children (53%) identified from an adult TB contact investigation.
      Of children with identified sources (n = 24, 67%), 23 (96%) had probable
      household transmission; 20 (83%) had a foreign-born relative from a TB-endemic
      country as the probable source. Seven (50%) of 14 adult sources investigated had
      a delayed TB diagnosis. In 2003, increased TB clinic staffing, more frequent
      pediatric TB clinics and on-site gastric aspirates for TB diagnosis contributed
      to 55% more children being evaluated for TB. CONCLUSIONS: Close interaction with
      family members and delayed diagnoses were the primary means of TB transmission to
      children. The increase in pediatric TB likely reflects improved clinic diagnostic
      capacity and may indicate a more accurate baseline rate for Maricopa County.
      Programmatic improvements in TB control and targeted outreach to high-risk
      immigrant populations may increase pediatric and adult source case detection and
      reduce Mycobacterium tuberculosis transmission.

PMID- 16462294
TI  - Multicity Italian study of congenital cytomegalovirus infection.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is the most frequent congenital
      infection in humans. Its prevalence and the frequency of disabling sequelae must
      be assessed in different populations to permit the formulation or assessment of
      preventive measures. OBJECTIVES: To check the prevalence of congenital infection
      and seroprevalence in Italy; to verify the rate of sensorineural hearing loss
      (SNHL) in infected infants; and to assess the proportion of children with SNHL
      attributable to congenital CMV infection. METHODS: Diagnosis of congenital CMV
      infection was sought in 9032 children born between March 2002 and February 2003
      by testing for viral DNA [CMV dried blood spot (DBS) test] in each newborn's
      Guthrie card and confirmation by isolation of CMV from urine collected in the
      first 3 weeks of life; CMV IgG testing in 1200 women of childbearing age;
      clinical and audiologic tests in the first 24 months for infected children; CMV
      DBS tests on the Guthrie cards collected from screening centers for 77 children
      (3 months-5 years) presenting SNHL of 40 dB or more. RESULTS: CMV infection was
      diagnosed in 14 asymptomatic and 2 symptomatic newborns (0.18%). CMV
      seroprevalence was 80%. In 2 infected infants, transient, unilateral SNHL was
      found. Nineteen of the 71 children with SNHL >70 dB were congenitally infected.
      CONCLUSIONS: The prevalence of congenital CMV infection is low in Italy.
      Population characteristics limiting the circulation of CMV strains in adult women
      might explain this. The fact that CMV contributes to significant SNHL highlights
      the need for preventive measures.

PMID- 16462295
TI  - Influenza pneumonia.
AB  - BACKGROUND: Influenza and pneumonia are common childhood illnesses, but few
      studies have been conducted on influenza-related pneumonia in children. The aim
      of this study was to describe the frequency and characteristics of laboratory
      documented and radiologically detected influenza pneumonia in children. METHODS:
      This study involved children treated at the Department of Pediatrics, Turku
      University Hospital, from 1980 through 2003. Influenza A or B infection was
      documented with the use of antigen detection from nasopharyngeal aspirates.
      Children with chest radiographs obtained during influenza episodes were
      identified. Chest radiographs were reevaluated by a pediatric radiologist for
      verification of pneumonic infiltrates. Clinical and laboratory data were
      collected from medical records. RESULTS: Pneumonia was detected in 134 (14%) of
      936 children with influenza infection. The most frequent signs of influenza
      pneumonia were fever and cough. Of these children, 47% had no specific clinical
      signs or symptoms suggesting pneumonia. White blood cell count was <15 x 10/L in
      89% and serum C-reactive protein concentration <80 mg/L in 85% of the children.
      One-half of the children had solely interstitial infiltrates, one-fourth solely
      alveolar and one- fourth both alveolar and interstitial infiltrates on the chest
      radiograph. The hospitalization rate was 68%, and the median duration of
      hospitalization was 2 days. Complicated pneumonias were rare, and mortality was
      low (0.7%). CONCLUSIONS: Pneumonia is detected in a minority of children treated
      for influenza at a tertiary center. Unlike in adults, influenza pneumonia in
      children is usually a benign illness, and the mortality is low.

PMID- 16462296
TI  - Infectious pericarditis in children.

PMID- 16462297
TI  - Prospects for active and passive immunization against Staphylococcus aureus.

PMID- 16462298
TI  - Neonatal babesiosis: case report and review of the literature.
AB  - A case of transfusion-associated neonatal babesiosis is presented. Jaundice,
      hepatosplenomegaly, anemia and conjugated hyperbilirubinemia developed in this
      preterm infant. The diagnosis was eventually made by blood smear, serology and
      polymerase chain reaction. The patient was treated with clindamycin and quinine
      and made a favorable recovery. Of neonatal babesiosis reported in the literature,
      9 other cases are reviewed, including 6 that were transfusion-associated, 2
      congenital and 2 tick transmitted.

PMID- 16462299
TI  - Diagnostic value of serum procalcitonin and C-reactive protein in Egyptian
      children with streptococcal tonsillopharyngitis.
AB  - We investigated serum procalcitonin (PCT) and C-reactive protein (CRP) in
      children with streptococcal tonsillopharyngitis or nonstreptococcal
      tonsillopharyngitis and in healthy children. The median (range) for PCT was 0.374
      (0.11-6.5), 0.105 (0.01-0.53) and 0.02 (0.01-0.08) ng/mL in the streptococcal,
      nonbacterial tonsillopharyngitis and control groups, respectively. PCT had a
      greater specificity than CRP for detection of bacterial tonsillopharyngitis.

PMID- 16462300
TI  - Serotypes and antimicrobial resistance of streptococcus pneumoniae in Thailand
      2002-2004.
AB  - Information on pneumococcal isolates is limited in Asia. Among children younger
      than 5 years in rural Thailand, nasopharyngeal colonization was 60%, and 55% of
      carried and 62% of invasive isolates were serotypes in the 7-valent pneumococcal
      conjugate vaccine. Nonsusceptibility was common among the serotypes included in
      the vaccine. Pneumococcal conjugate vaccine might be a useful prevention tool in
      Thailand.

PMID- 16462301
TI  - Economic impact of the community-acquired methicillin-resistant Staphylococcus
      aureus epidemic on the Driscoll Children's Health Plan.
AB  - Cellulitis and abscess accounted for increasing percentages of inpatient (4.6
      11.1%), outpatient (0.6-1.2%) and total (1.7-3.3%) expenses from 2001 through
      2004. The per member per month expenses attributed to cellulitis and abscess
      increased from $0.74 in 2001 to $1.19 in 2004. The epidemic of community-acquired
      methicillin-resistant Staphylococcus aureus infections in children has had a
      significant economic impact on the Driscoll Children's Health Plan.

PMID- 16462302
TI  - Failure of a 5-day course of intramuscular ceftriaxone to eradicate Streptococcus
      pneumoniae from the middle ear.
AB  - A 10-kg 9-month-old infant with recurrent, unresponsive otitis media presented
      with bilateral acute otitis media caused by Streptococcus pneumoniae type 19A,
      resistant to all oral agents and intermediately susceptible to ceftriaxone.
      Treatment with myringotomies and intramuscular ceftriaxone, 50 mg/kg/d for 5
      days, was unsuccessful. The patient responded to pressure equalization tubes and
      local ciprofloxacin with dexamethasone drops.

PMID- 16462303
TI  - Primary lung abscess caused by multidrug-nonsusceptible Streptococcus pneumoniae
      in a child.
AB  - We report a 21-month-old boy with primary lung abscess caused by multidrug
      nonsusceptible Streptococcus pneumoniae. A computed tomography-guided aspirate
      obtained on admission grew penicillin-, ceftriaxone-, erythromycin- and
      clindamycin-nonsusceptible S. pneumoniae. The patient was treated for 10 days
      with parental rifampin and cefotaxime and then for 4 weeks with oral cefpodoxime
      and recovered without complications.

PMID- 16462304
TI  - Severe gynecomastia in an African boy with perinatally acquired human
      immunodeficiency virus infection receiving highly active antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) slows the progression of human
      immunodeficiency virus (HIV) disease and lowers mortality and morbidity in
      children. Coincident with these advances, an increasing number of side effects
      are being reported. We describe an adolescent boy with perinatally acquired HIV
      infection who developed significant bilateral breast enlargement as a result of
      HAART. He required bilateral mastectomies. Pediatricians need to be aware of less
      common side effects of HAART.

PMID- 16462305
TI  - Antiphospholipid syndrome in a human immunodeficiency virus 1-infected child.
AB  - High prevalence of anticardiolipin antibodies and antiphospholipid antibodies has
      been reported in human immunodeficiency virus (HIV)-infected patients. A full
      blown clinical picture of antiphospholipid syndrome (APLS) is rare and rarely
      reported, even in HIV-infected adults and has never been reported in HIV-infected
      children. We report an HIV-infected child with left sided choreoathetosis
      associated with APLS.

PMID- 16462306
TI  - Pneumonia with marked pleural effusion caused by Aspergillus infection.
AB  - We present a case of pneumonia with marked pleural effusion caused by Aspergillus
      infection in a 2-year-old Japanese girl with Down's syndrome. The patient was
      previously diagnosed with acute myeloid leukemia, developing the pneumonia during
      induction treatment. Although no pathogens could be isolated from any clinical
      specimens, 135,000 copies/mL of Aspergillus DNA were detected in the pleural
      fluid using real time polymerase chain reaction. The copy numbers of DNA
      decreased rapidly after appropriate antifungal treatment.

PMID- 16462307
TI  - Salmonella septic sacroiliitis: case report and review.
AB  - A 14-year-old girl living on a farm developed Salmonella septic sacroiliitis 3
      weeks after eating cake batter. An abnormal magnetic resonance image coupled with
      Salmonella-positive stool and sacroiliac synovial fluid cultures facilitated the
      diagnosis. She was successfully treated. Twenty-three other cases of Salmonella
      sacroiliitis are reviewed and reveal a disease primarily of adolescents with a
      consistent presentation and favorable treatment response.

PMID- 16462308
TI  - Resistant Mycobacterium bovis disseminated infection.

PMID- 16462309
TI  - Reconstruction of a posttrauma arthritic distal radioulnar joint by vascularized
      second metatarsophalangeal joint transfer.

PMID- 16462310
TI  - Managing pyoderma gangrenosum: a synergistic approach combining surgical
      debridement, vacuum-assisted closure, and hyperbaric oxygen therapy.

PMID- 16462311
TI  - The pathogenesis of hemangiomas: a review.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Differentiate between hemangiomas and vascular malformations. 2. Describe
      arguments for the trophoblast origin of hemangiomas. 3. Give arguments for the
      angioblast theory for the origin of hemangiomas. 4. Identify key genes involved
      in the origin of hemangiomas. BACKGROUND: Hemangiomas of infancy are common
      endothelial tumors. They differ from vascular malformations in their tissue
      architecture and biological properties. To date, there is no universally accepted
      theory that explains the pathogenesis and pathophysiology of hemangiomas.
      METHODS: Theories from the medical literature from 1981 to 2004 were gathered,
      categorized, and reviewed. RESULTS: Current research is mostly on the cellular
      and genetic levels. The most authoritative theories focus on angioblast origins,
      trophoblast origins, mutations in cytokine regulatory pathways, and field defects
      as the cause of the deranged angiogenesis of hemangiomas. CONCLUSIONS: To date,
      no single theory can easily explain all the characteristics of hemangiomas, such
      as predilection for the female sex, usual occurrence after birth, spontaneous
      involution, abnormal tissue architecture, and distribution within a developmental
      field. Hemangiomas are probably the final common expression of several
      pathophysiological mechanisms taking effect alone or in combination.

PMID- 16462312
TI  - Prospective study of outcomes after reduction mammaplasty: long-term follow-up.
AB  - BACKGROUND: The purpose of this prospective study was to determine whether the
      beneficial effects of reduction mammaplasty are maintained over the long term in
      a Canadian population and to determine whether reduction mammaplasty facilitates
      weight loss in the overweight patient. METHODS: The Short Form-36, Rosenberg Self
      Esteem Scale, and Symptom Inventory Questionnaire were used to assess 57 patients
      preoperatively and postoperatively at 6 months and 21.5 months. Surgeons
      completed preoperative, operative, and postoperative patient assessment forms to
      collect anthropometric, procedural, and postoperative complication data. RESULTS:
      Stable and significant improvements were found in all three outcomes
      questionnaires when compared preoperatively and 6 and 21.5 months
      postoperatively. The Short Form-36 indicated significant improvements (p < 0.05)
      in seven of the eight health status domains and the physical summary score,
      suggesting that the procedure primarily benefits physical aspects of health.
      Scores also improved on the Rosenberg Self-Esteem Scale (p < 0.0001) and symptoms
      improved on the Symptom Inventory Questionnaire (p < 0.0001) in patients 6 and
      21.5 months after reduction mammaplasty. The patients had significant health
      deficits preoperatively compared with the normal population. Preoperative mean
      Short Form-36 scores were significantly lower in several areas (p < 0.005). The
      health deficits were eliminated at 6 months and showed a normalization effect at
      21.5 months. Patients with a body mass index greater than 27 kg/m (n = 26; 1 kg =
      2.2 lbs.) showed a significant decrease in weight and body mass index at long
      term follow-up at 21.5 months postoperatively (p < 0.003). CONCLUSIONS: The long
      term results of reduction mammaplasty indicate that this procedure is an
      effective method to reduce or alleviate both physical and psychological symptoms
      associated with macromastia. This study shows that this procedure should be
      covered under Canadian medical insurance plans.

PMID- 16462313
TI  - Implant reconstruction in breast cancer patients treated with radiation therapy.
AB  - BACKGROUND: Implant reconstruction in breast cancer patients treated with
      radiation therapy is controversial. Prior studies are limited by older prosthetic
      devices, reconstructive techniques, and radiation therapy protocols. METHODS: A
      retrospective review was performed of patients who underwent tissue expansion and
      implant breast reconstruction performed by a single surgeon after mastectomy for
      breast cancer from 1996 to 2003. Complications and aesthetic results were
      compared between patients who received radiation therapy and those who did not.
      RESULTS: A total of 104 patients (123 breasts) who underwent mastectomy and
      implant breast reconstruction were included in the study. Twenty-seven patients
      (27 breasts) received either premastectomy or postmastectomy radiation therapy
      for breast cancer. All patients who received radiation therapy did so before
      completion of their implant reconstruction. Complications ultimately requiring
      prosthetic device removal or replacement, as well as total complications (those
      requiring prosthetic removal or replacement and those not requiring prosthetic
      removal or replacement), were more frequent in breasts that received radiation
      than breasts that did not (18.5 percent versus 4.2 percent for complications
      requiring prosthetic removal or replacement, p < or = 0.025, and 40.7 percent
      versus 16.7 percent for total complications, p < or = 0.01). Breast symmetry was
      significantly better in patients who did not receive radiation compared with
      those who did (p < 0.01). CONCLUSIONS: Implant breast reconstruction in patients
      who receive radiation therapy is possible but associated with more frequent
      complications and decreased aesthetic results. However, the present results
      compare favorably to those reported in prior studies. Improved results in the
      present study may be attributable to the use of newer prostheses, staged breast
      reconstruction with initial tissue expansion, total muscular coverage of the
      implant, and modern radiation therapy protocols.

PMID- 16462314
TI  - Therapeutic mammaplasty for centrally located breast tumors.
AB  - BACKGROUND: Central breast tumors are difficult to manage using breast-conserving
      treatment. Mastectomy has often been cited as the favored option for these
      tumors, because lumpectomies that remove the nipple-areola complex often result
      in poor cosmesis. This article describes the use of therapeutic mammaplasty (a
      term used to describe breast reduction techniques utilized to treat breast
      cancer) for centrally sited breast tumors. METHODS: The techniques can be broadly
      divided into two categories: (1) wedge excision, involving wedge excision and a
      form of wedge closure, and (2) advancement flaps with nipple reconstruction.
      RESULTS: These techniques were used in 11 patients. Excision margins were
      complete in all cases except one, due to extensive ductal carcinoma in situ.
      There have been no other complications and no cases of recurrence to date.
      CONCLUSIONS: When compared with mastectomy and total reconstruction, therapeutic
      mammaplasty has cosmetic, functional, and recovery time advantages. The
      techniques described need further evaluation and long-term follow-up. However,
      they can be added to the repertoire of techniques already established for breast
      conserving surgery.

PMID- 16462315
TI  - The vertical reduction mammaplasty: a prospective analysis of patient outcomes.
AB  - BACKGROUND: In the United States, breast reductions based upon a Wise pattern
      incision remain common. However, dissatisfaction with this procedure, on the part
      of the patient and the surgeon alike because of unsightly scars and long-term
      "bottoming out" of the breast, has promoted the search for alternative methods of
      breast reduction. The purpose of this study was to analyze patient outcomes after
      vertical reduction mammaplasty utilizing prospectively collected data. METHODS:
      All patients were given a custom-designed questionnaire designed to evaluate
      their macromastia-related symptoms and other macromastia-related quality-of-life
      issues. Patients were then provided the same questionnaire at their final
      postoperative visit between 3 and 6 months after surgery. RESULTS: A total of 63
      patients underwent vertical reduction mammaplasty and 40 patients underwent Wise
      pattern inferior pedicle reduction mammaplasty. Vertical reduction mammaplasty
      resulted in significant decreases in all macromastia-related symptoms analyzed,
      including upper back pain, lower back pain, neck pain, arm pain, shoulder pain,
      hand pain, breast pain, headaches, rashes and/or itching, and painful brassiere
      strap grooving (all, p < 0.00001). Furthermore, vertical reduction mammaplasty
      resulted in significant improvement in all quality-of-life factors analyzed,
      including difficulty buying clothes and brassieres, difficulty playing sports,
      and difficulty running (all, p < 0.00001). Minor complications (superficial
      infection, seroma, or delayed wound healing) occurred in 16 patients (25 percent)
      in the vertical reduction mammaplasty group. Minor office revisions (scar
      revision or excision) were performed in four patients (6 percent) in the vertical
      reduction mammaplasty group. CONCLUSION: The authors' method of vertical
      reduction mammaplasty offers substantial relief of macromastia-associated
      symptoms with a low complication/revision rate.

PMID- 16462317
TI  - The frontal-temporal nerve triangle: a new concept of locating the motor and
      sensory nerves in upper third of the face rhytidectomy.
AB  - BACKGROUND: How to avoid damage to the temporal branch of the facial nerve has
      long been a central topic of discussion. Recently, damage to the supraorbital
      nerve, the auriculotemporal nerve, and other branches of the trigeminal nerve
      divisions has attracted much attention. Focusing on frontal and temporal
      rhytidectomy, the authors have investigated the course and distribution of the
      facial nerve branches, the supraorbital nerve, the auriculotemporal nerve, and
      other branches of trigeminal division. In this article, they present the concept
      of the frontal-temporal nerve triangle; its contents, vicinity, and clinical
      significances are discussed. METHODS: An anatomical study was performed using 30
      temporal-parietal regions of 10 fixed adult cadavers and five fresh cadavers. A
      step-by-step dissection from the superficial layer to the deep layer was
      involved; all the measurement data were analyzed, and the mean and standard
      deviation were calculated and expressed in centimeters. RESULTS: The frontal
      temporal nerve triangle is an approximately triangular area formed by the
      temporal branch of the facial nerve, the supraorbital nerve, and the
      auriculotemporal nerve. Together with its contents and vicinal structures, it
      forms a complicated three-dimensional rather than two-dimensional structure.
      Anatomical structures closely associated with rhytidectomy are located in or near
      this area. CONCLUSIONS: Acting as the anatomical body surface landmark for
      preoperatively locating the temporal branch, the supraorbital nerve, the
      auriculotemporal nerve, and its related structures, the concept of the frontal
      temporal nerve triangle has practical significance in designing incisions and
      selecting planes of dissection in upper third of the face rhytidectomy.

PMID- 16462318
TI  - Management of intraoperative fractures of the nasal septal "L-strut":
      percutaneous Kirschner wire fixation.
AB  - BACKGROUND: The area where the septal cartilage joins the perpendicular plate of
      the ethmoid is a vulnerable region where overresection or disruption during
      rhinoplasty causes a loss of support and potential collapse of the nasal dorsum,
      leading to a saddle-nose deformity. Previously described methods of repair
      involve suture techniques that are often inadequate to restore septal stability.
      The authors present the senior author's (J. P. G.) experience in managing
      intraoperative fractures of the septal "L-strut," describe a classification
      system for the types of dorsal septal L-strut fractures, and present a new method
      of treatment using percutaneous Kirschner wire fixation. METHODS: The authors
      conducted a retrospective review of 1372 primary and secondary rhinoplasties
      performed by the senior author. A classification system was developed to describe
      the type and location of dorsal septal L-strut fractures. Each patient was
      treated with immediate restabilization of the fractured dorsal septal L-strut
      with dorsal spreader grafts, percutaneous Kirschner wire fixation, or a
      combination of both methods. RESULTS: Seventeen patients sustained an
      intraoperative fracture of the septal L-strut with an overall incidence of 1.2
      percent. Complications included minor dorsal deviation and inadequate
      reduction/moderate dorsal depression in three patients requiring revision surgery
      to correct the dorsal deformities. CONCLUSIONS: An intraoperative fracture of the
      septal L-strut is a rare but unfortunate occurrence during rhinoplasty. Although
      technically difficult to perform, the percutaneous Kirschner wire fixation
      technique with or without spreader grafts is a novel and effective approach to
      this complication.

PMID- 16462319
TI  - The L brachioplasty: an innovative approach to correct excess tissue of the upper
      arm, axilla, and lateral chest.
AB  - BACKGROUND: Brachioplasty is aesthetic reshaping of the upper arm after removal
      of excess medial skin and fat. Massive weight loss patients evolve a severe arm
      deformity that extends through the axilla and onto the chest. Prevalent
      operations are incomplete and leave conspicuous scars along the bicipital groove
      that end as Ts or Zs in the axilla. The L brachioplasty starts with a long
      ellipse centered over the lower half of the inner arm that sweeps up to the
      deltopectoral groove. A shorter ellipse is connected at right angles through the
      axilla onto the chest. The V flap formed between the ellipses is advanced across
      the axilla to raise the posterior axillary fold. An improved arm, axilla, and
      chest have an L-shaped zigzag crossing the axilla. METHODS: L brachioplasty,
      along with upper body lifting, was applied to 24 female weight loss patients over
      the last 2 years. Ultrasound-assisted lipoplasty was also performed in five
      patients. All patients were interviewed. Follow-up ranged from 6 to 28 months.
      RESULTS: All 22 patients were improved and pleased. One patient requested and
      received a limited scar revision. Three patients had delayed healing at the tip
      of the triangular flap. Four seromas near the elbow responded to multiple
      aspirations. One hypertrophic scar was improved with intense pulsed light.
      CONCLUSIONS: The L-shaped brachioplasty is an innovative, effective, reliable,
      aesthetic, and safe technique. Integrating the brachioplasty into the upper body
      lift improves the contours of the axilla, breast, and upper lateral chest,
      contributing to improved harmonious body contour.

PMID- 16462321
TI  - Body lift: an account of 200 consecutive cases in the massive weight loss
      patient.
AB  - BACKGROUND: The epidemic of obesity in the United States has led to a rapid
      increase in the number of bariatric procedures performed over the past several
      years. The dramatic changes to the torso following massive weight loss are only
      partially addressed by routine procedures such as abdominoplasty and liposuction.
      Circumferential body lifts or simultaneous abdominoplasty, thigh, and buttock
      lifts are becoming the method of choice for treating the postbariatric condition.
      In this article, the authors review the senior author's experience of 200 body
      lifts with massive weight loss individuals. METHODS: The charts of 200
      consecutive body lift patients were reviewed for complications and other
      variables. The preoperative markings, current surgical technique, and
      postoperative care are described. The patients were classified into three types
      according to their body mass index at the time of surgery. Type I individuals had
      a body mass index less than 28, type II individuals had a body mass index between
      28 and 32, and type III individuals had a body mass index greater than 32.
      RESULTS: Type I and II patients in many instances achieved a nearly ideal body
      contour. Type II and III individuals also had a significant functional and
      aesthetic improvement but were more likely to have complications. The overall
      complication rate was 50.0 percent. The most frequent complications were skin
      dehiscence and seroma formation at 32.5 percent and 16.5 percent, respectively.
      CONCLUSIONS: The body lift very effectively addresses the functional and
      aesthetic concerns of the massive weight loss patient. Careful patient selection
      and education are essential to a good outcome.

PMID- 16462322
TI  - Fluid resuscitation in liposuction: a retrospective review of 89 consecutive
      patients.
AB  - BACKGROUND: In 1998, the senior author presented the intraoperative fluid ratio,
      defined as the volume of super-wet solution and intraoperative intravenous fluid
      divided by the aspiration volume, to guide resuscitation fluid volumes in super
      wet liposuction. The senior author demonstrated that intraoperative fluid ratios
      of 2.1 for small-volume and 1.4 for large-volume liposuction were safe and did
      not cause volume overload sequelae. A high urine output was common and reflected
      a mild overresuscitation, which could have adverse consequences in patients with
      undiagnosed cardiopulmonary disease. The purpose of this study was to compare
      overresuscitation sequelae in a cohort of consecutive super-wet liposuction
      patients using a new fluid management formula in which replacement fluid was
      given after 5000 cc of lipoaspirate instead of 4000 cc, as initially described.
      METHODS: The charts of 89 consecutive patients undergoing super-wet liposuction
      were retrospectively reviewed. RESULTS: The intraoperative fluid ratio was 1.8
      for the small-volume reductions (< 5000 cc, n = 68) and 1.2 (> 5001 cc, n = 21)
      for the large-volume reductions. There were no episodes of pulmonary edema,
      congestive heart failure exacerbation, or other major complications. The average
      urine output in the operating room, the recovery room, and while on the floor was
      1.5, 1.6, and 2.9 cc/kg/hour for the small-volume group and 1.7, 1.8, and 2.5
      cc/kg/hour for the large-volume group. CONCLUSIONS: The super-wet subcutaneous
      infiltration liposuction technique for both small- and large-volume reductions is
      safe and can be performed without adverse cardiopulmonary sequelae. Given the
      high urine outputs, the intraoperative fluid ratio can be further improved by
      possibly eliminating the replacement fluid altogether.

PMID- 16462323
TI  - Top-10 list of herbal and supplemental medicines used by cosmetic patients: what
      the plastic surgeon needs to know.
AB  - BACKGROUND: Widespread use of herbal medications/supplements among the
      presurgical population may have a negative effect on perioperative patient care.
      Thus, the authors' goal was to identify the prevalence of such use in a cosmetic
      surgery patient population compared with use among the general public; to assess
      physician awareness of proper management of these herbal medications/supplements;
      and to review the literature to provide rational strategies for managing
      perioperative patients taking these remedies. METHODS: To assess patient (n =
      100) and general public (n = 100) usage rates, open-ended lists of (1) the most
      common herbal medications/supplements and (2) homeopathic treatments were
      compiled. Board-certified plastic surgeons (n = 20) were then given the same list
      of herbs/supplements and surveyed on their awareness of these treatments and
      perioperative side effects. RESULTS: The usage rate for cosmetic versus public
      surveys for herbal medicines/supplements was 55 percent versus 24 percent (p <
      0.001), with 35 percent versus 8 percent (p < 0.001) engaging in homeopathic
      practices, respectively. Cosmetic patients' top four herbal/supplements of usage
      were chondroitin (18 percent), ephedra (18 percent), echinacea (14 percent), and
      glucosamine (10 percent). The top four used by the general public were echinacea
      (8 percent), garlic (6 percent), ginseng (4 percent), and ginger (4 percent). The
      physician survey demonstrated awareness of 54 percent of the listed
      supplements/herbal medicines, 85 percent of which were not suggested to be
      discontinued preoperatively, with only ephedra achieving 100 percent physician
      discontinuation preoperatively. CONCLUSIONS: Herbal medicines and supplements
      displayed greater prevalence in the cosmetic surgery population than in the
      population at large. Furthermore, side effects and potential complications
      warrant addressing these remedies as pharmaceuticals rather than as safe and
      "natural." Thus, a descriptive "top-10" list with perioperative recommendations
      was compiled for the plastic surgeon.

PMID- 16462325
TI  - Favorable morphologic change of preosteoblasts in a three-dimensional matrix with
      in vitro microdistraction.
AB  - BACKGROUND: Distraction osteogenesis has been used to correct hypoplastic and
      asymmetric bony deformities in the growing patient, yet its underlying cellular
      mechanisms are poorly understood. Using a new in vitro model, the
      microdistractor, morphologic properties of preosteoblasts under mechanical strain
      were studied. METHODS: Mouse calvarial MC3T3 cells were suspended in a
      polymerized three-dimensional collagen gel and stressed for 14 days as one of
      three groups (n = 30): (1) distraction (0.5 mm/day); (2) oscillation (1 mm/day
      for 2 days alternated with 1 mm/day for 2 days); and (3) control (no force). A
      computer modeling system, KS-300, was used to record cell shape (aspect ratio)
      and orientation (deviance from axis of stress). RESULTS: In part I of the study,
      morphologic cellular changes were found to be even throughout different regions
      of the gel (central versus peripheral, versus different vertical layers),
      suggesting the force was evenly applied to all cells in the gel. In addition,
      when linear distraction forces were applied, morphologic change occurred over
      time, suggesting a morphologic response to the applied stress. In part II of the
      study, with different forces applied, morphologic changes occurred over time such
      that linear distraction forces caused cells to elongate and align in a parallel
      direction to the force, whereas oscillation caused cells to switch from parallel
      (with distraction) to perpendicular (with compression) orientation relative to
      the force applied. CONCLUSION: The authors' data suggest that the microdistractor
      device is an effective in vitro model for studying the cellular response to
      distraction stresses. It may be used in future studies to optimize clinical
      methods of distraction.

PMID- 16462327
TI  - Versatility of botulinum toxin: a use in stabilization of pedicled muscle flaps.
AB  - BACKGROUND: In this study, botulinum toxin A was used to secure the stabilization
      of muscle flaps without denervation atrophy. METHODS: Thirty adult female Wistar
      rats were divided into a control group (group I, n = 10), a denervation group
      (group II, n = 10), and a botulinum toxin A group (group III, n = 10). In all of
      the groups, pedicled pectoralis major muscle flaps were elevated from the sternal
      attachment on the right side. In the second group, muscle flaps were denervated
      by transsecting the pectoralis major nerve after flap elevation; in the third
      group, botulinum toxin A (1.4 U of Dysport; Ipsen, Maidenhead, United Kingdom)
      was injected into the prepared muscle flap before flap replacement. The distance
      between the medial side of the muscle and the midline was measured at 4 weeks.
      Histopathological examination was performed 10 weeks after the first operation.
      The diameter of the muscle fibers was measured, and the degree of atrophy in the
      muscle flaps was evaluated in all groups. RESULTS: Mean distances from the
      midline were statistically significantly different in all of the groups (p =
      0.000, p < 0.01). There was a significant difference in muscle fiber diameter
      among the groups (p = 0.000, p < 0.01). Temporary denervation by botulinum toxin
      A and irreversible denervation with transsection of the motor nerve caused the
      reduced diameters of the muscle fibers. In addition, moderate to severe muscle
      atrophy in group II and mild to moderate muscle atrophy in group III were
      observed. CONCLUSIONS: In the pedicled muscle flaps, botulinum toxin A can be
      used easily and reliably for stabilization. It was concluded that detachment of
      the muscle flap might be prevented and operative morbidity decreased using this
      method.

PMID- 16462328
TI  - Human circulating peripheral blood mononuclear cells for calvarial bone tissue
      engineering.
AB  - BACKGROUND: Large-scale production of engineered tissues requires an adequate
      source of expandable cells. Current strategies that involve harvesting of cells
      from donor tissue or bone marrow for tissue engineering are invasive and
      unfeasible for obtaining large quantities of cells in a clinical setting.
      Peripheral blood has been reported to contain circulating hematopoietic cells as
      well as, in significantly smaller quantities, mesenchymal cells METHODS: An
      adherent subset of CD14+ mononuclear cells was isolated from human peripheral
      venous blood and characterized in vitro by light microscopy,
      immunohistochemistry, flow cytometry, and quantitative differentiation assays.
      These cells were then evaluated for the purposes of tissue engineering in a rat
      calvarial defect model, in combination with biodegradable polymer matrices made
      from poly-e-caprolactone. Specimens were analyzed 6 weeks after implantation with
      histologic analysis, microcomputed tomography, and HLA immunostaining. RESULTS:
      CD14+ mononuclear cells were induced to differentiate into osteoblast-like cells
      in vitro, with areas of mineralization. In a rat calvarial defect model, tissue
      engineered bone with evidence of mineralization was formed within 6 weeks. HLA
      immunohistochemistry demonstrated that de novo bone formation originated from the
      transplanted human cells. CONCLUSIONS: These findings show, for the first time,
      to our knowledge, the derivation of bone from human blood. They also demonstrate
      the utility of circulating mononuclear cells as a minimally invasive, potentially
      unlimited pool of cells for tissue engineering and organ regeneration.

PMID- 16462329
TI  - A supermicrosurgical flap model in the rat: a free true abdominal perforator flap
      with a short pedicle.
AB  - BACKGROUND: Perforator flaps have recently gained considerable popularity in
      reconstructive surgery, and their importance and advantages over conventional
      flaps have been widely accepted. Given the improvements in microsurgical
      techniques, researchers have encouraged the search for further perforator flap
      sources, such as a perforator flap with a short pedicle only. The purpose of this
      study was to describe a true perforator flap model with a short vascular pedicle
      in the abdominal region in the rat. METHODS: Twenty-six adult Sprague-Dawley rats
      weighing 400 to 500 g were used. In 10 rats, the perforator vascular anatomy of
      the abdominal region was determined by anatomic dissection. In the remaining 16
      rats, a true abdominal perforator-based flap was created based on a short segment
      of deep epigastric vessels. In eight rats, the flap was transferred to the groin
      region as a free flap, and anastomosis was performed between the artery and vein
      of the flap and the superficial inferior epigastric artery and vein of the
      recipient site. In addition, in two of these flaps, the long thoracic vein of the
      flap was anastomosed to the femoral vein. In the remaining eight rats, the flap
      was transferred to the groin region, but in this group anastomosis was not
      performed. The latter group was designated as the control group. RESULTS: The
      skin islands of seven free perforator flaps survived completely, and the one
      remaining flap was determined to be necrotic. All the flaps in the control group
      underwent complete necrosis. CONCLUSIONS: Not only is the free abdominal
      perforator flap a reliable and true perforator flap model for future
      physiological, biological, and pharmacological studies, it is also an excellent
      self-controlled supermicrosurgical training model for learning proper techniques,
      meticulous intramuscular dissection of true perforator flaps, and anastomosis of
      small-caliber vessels.

PMID- 16462330
TI  - Comparison of elongations provided by subcutaneous pedicle rhomboid flap and Z
      plasty in rat inguinal skin.
AB  - BACKGROUND: The most commonly used technique in the treatment of contracture
      bands is Z-plasty. The subcutaneous pedicle rhomboid flap is a relatively new
      flap whose efficiency in the treatment of wide or linear contractures with two or
      more contracture bands has been demonstrated. This experimental study was planned
      to compare the lengthening provided by the subcutaneous pedicle rhomboid flap
      with that provided by the Z-plasty. METHODS: The lower extremities of 10 male
      Sprague-Dawley rats were strained by hanging 500 g of weight to create tension
      lines over both inguinal areas. Z-plasty, with a 1-cm central limb and 60-degree
      angles, was planned over the inguinal tension line on one side. On the other
      side, a subcutaneous pedicle rhomboid flap was sketched, with a 1-cm-long axis
      and inner 60-degree angles located over the tension line. In the Z-plasty
      technique, triangular flaps were elevated over the muscle, transposed, and
      sutured. In the subcutaneous pedicle rhomboid flap technique, the flap was
      incised down to the muscle and freed from the tension line, which was later
      relieved by relaxation incisions. The resulting defects were then closed by
      suturing the rhomboid flap in V-Y advancement along the tension line and in Y-V
      advancement along the relaxation incisions. The final lengthening provided by
      both techniques was measured, and the results were analyzed statistically.
      RESULTS: Both techniques were effective in relieving tension over the inguinal
      areas and in lengthening the tension lines. The lengthening provided by Z
      plasties with 1-cm central limbs ranged from 3 to 3.8 cm. The difference between
      preoperative and postoperative Z-plasty measurements ranged from 2.0 to 2.8 cm
      (mean +/- SD, 2.43 +/- 0.28 cm). The lengthening provided by the flaps with 1-cm
      axes ranged from 3.9 to 5.0 cm and the difference in measurements before and
      after surgery ranged from 2.9 to 4.0 cm (3.27 +/- 0.33 cm). Statistical analysis
      revealed that the elongation provided by the subcutaneous pedicle rhomboid flap
      was longer than that provided by Z-plasty (p < 0.0001). CONCLUSION: The
      subcutaneous pedicle rhomboid flap technique is a more effective than Z-plasty in
      lengthening the tension lines in rat inguinal skin.

PMID- 16462331
TI  - Radial collateral ligament repair of the thumb metacarpophalangeal joint using
      the abductor pollicis brevis tendon.
AB  - BACKGROUND: Injuries to the radial collateral ligament of the thumb
      metacarpophalangeal joint are less common than injuries to the ulnar side.
      Therefore, published data on this subject are scarce. An innovative method of
      radial collateral ligament repair is hereby presented, placing emphasis on the
      long-term results. This technically simple method was developed to allow for a
      biological joint stabilization based on functional and anatomical considerations.
      The key concept is to reestablish joint stability by spanning the tendinous
      portion of the insertion of the abductor pollicis brevis over the radial side of
      the metacarpophalangeal joint. METHODS: Nine patients with rupture of the radial
      collateral ligament were treated by means of the abductor pollicis brevis-plasty.
      All patients suffered from subacute or chronic radial ligament insufficiency. To
      determine the subjective results of the repair, a score was developed grading the
      patient's ranking of the results achieved by the abductor pollicis brevis-plasty.
      All patients graded the results on a scale from 1 (excellent) to 6
      (unacceptable). RESULTS: Patients were operated on 37.1 +/- 14.6 days after
      trauma. Long-term examination was performed after 39 +/- 14.5 months. The
      patients showed a high satisfaction score of 1.7 +/- 0.5, with good mobility of
      the metacarpophalangeal I joint (range of motion, 52.2 +/- 6.7 degrees).
      CONCLUSION: Favorable results suggest that the abductor pollicis brevis-plasty is
      a suitable, safe, and technically feasible procedure for the operative treatment
      of chronic instability of the thumb metacarpophalangeal joint after radial
      hyperadduction trauma and complete rupture or deinsertion of the radial
      collateral ligament.

PMID- 16462332
TI  - Biomechanics of the membranous flexor tendon sheath: the role of Grayson's
      ligaments.
AB  - BACKGROUND: The biomechanical integrity of the tendon sheath of the fingers has a
      significant effect on the success of flexor tendon surgery. As nonweightbearing
      elements, the membranous parts of the sheath have received little attention, and
      their contribution to sheath movement is still obscure. The authors presumed that
      Grayson's ligaments, which have been described as force-transmitting elements,
      might play a role in the biomechanics of the membranous flexor tendon sheath.
      METHODS: Twenty-two long fingers of cadaver hands were examined. The authors
      studied the movements of the inner aspect of the tendon sheath and the positions
      and patterns of the septa of the palmar soft tissues on picrosirius red-enhanced
      sagittal and transverse sections and hematoxylin and eosin-stained light
      microscopy specimens. RESULTS: The movements of the membranous flexor tendon
      sheath are controlled by subcutaneous structures. The septal patterns of the
      palmar fat pads indicate the existence of a highly flexible subcutaneous fibrous
      system in which the deformable fat pad keeps the force-transmitting elements
      tight. Collagen bundles in the microscopy specimens, which frequently form layers
      within the septa, are thought to correspond to Grayson's ligaments. The
      subcutaneous fibrous system adheres predominantly to the membranous parts of the
      flexor tendon sheath. CONCLUSIONS: Folding of the membranous flexor tendon sheath
      is guided by the subcutaneous fibrous system, of which the macroscopically
      dissectible elements are Grayson's ligaments. The current surgical approaches
      might have a deteriorating effect on the biomechanics of the flexor tendon
      sheath.

PMID- 16462333
TI  - Recovery of disused replanted digits by second toe hemipulp flap transfer.
AB  - BACKGROUND: Amputation of the distal phalanx is the most common among all
      mutilation injuries. Generally, it has been believed that the prognosis of this
      type of amputation is satisfactory; however, disuse of digits because of severe
      atrophy and sensory disturbances is frequently observed in the follow-up period.
      METHODS: The authors intended to use the second toe hemipulp flap for recovery of
      these disused digits and transferred the flaps to eight severely atrophic
      postreplanted digits. Objective sensory recovery was assessed along with
      estimation of the "usefulness" of the reconstructed fingers. RESULTS: No
      complications were observed postoperatively, and estimations of the functional
      results were almost satisfactory. CONCLUSION: This procedure significantly
      improved the prognosis of the replantation of severely crushed digits.

PMID- 16462334
TI  - From birth to maturity: a group of patients who have completed their protocol
      management. Part II. Isolated cleft palate.
AB  - BACKGROUND: The optimal management of the cleft palate patient from birth to
      completion of treatment continues to present a formidable challenge to the
      plastic surgeon. The management by multidisciplinary teams is well established,
      but long-term outcome data of cases managed by protocol remain sparse. This study
      continues to present the results of the Australian Craniofacial Unit of patients
      with isolated cleft palate who completed protocol management at the unit under
      the care of the senior author (D.J.D.) during the 29-year period from 1974 to
      2003. METHODS: A retrospective study of the outcomes in relation to facial
      growth, speech, hearing, and occlusion is presented of patients with an isolated
      cleft palate. RESULTS: Thirty-two cases were identified from the departmental
      database, involving 17 female patients and 15 male patients. Cephalometric
      analysis at skeletal maturity revealed a range of facial growth, and maxillary
      advancement surgery was deemed necessary in just two cases. Speech results were
      evaluated using speech therapy assessments during development and at maturity. At
      maturity, 18 of 32 patients were assessed as being within normal limits. The
      hearing was within -20 dB, with just two exceptions. CONCLUSION: Overall, these
      is a range of outcomes, but the results confirm that facial growth does not
      appear to be adversely affected by use of the pushback technique to reconstruct
      the palate.

PMID- 16462335
TI  - Synchronous palatal closure and premaxillary setback in older children with
      bilateral complete cleft of lip and palate.
AB  - BACKGROUND: Achieving good results after primary repair in older children with
      complete bilateral cleft lip and palate is a Herculean task, particularly when
      the premaxilla is protruding and twisted. The authors faced the problems of
      protruding premaxilla in children older than 5 years of age with bilateral
      complete cleft lip and palate who presented late for primary repairs. Due to
      financial constraints and the distances traveled, these patients prefer to come
      for fewer procedures with maximum benefits. These factors encouraged the authors
      to carry out synchronous palatal closure and premaxillary setback in older
      children with bilateral complete cleft of the lip and palate. METHODS:
      Synchronous palatal repair and premaxillary setback were carried out in 14
      patients. During palate repair, good exposure of the vomer made premaxillary
      setback easy without compromising the blood supply to it. The premaxilla, after
      osteotomy, was immobilized in all patients using the simple technique of
      Kirschner wire fixation; an additional gingivoperioplasty was performed in a few
      patients. Palatal closure was achieved with two flap techniques with intravelar
      veloplasty. RESULTS: Proper positioning of the premaxilla was achieved in all
      patients, with good labial repair 6 months after the primary palate closure.
      There were no major complications, such as loss of the premaxilla or vascular
      compromise. Two patients had an anterior open bite and one patient had a
      postalveolar fistula. CONCLUSIONS: This technique had a few minor complications,
      but the overall surgical outcome was satisfactory. This protocol proved
      advantageous in achieving good results with fewer procedures and in reducing the
      total expenditures and the length of the patient's hospital stay.

PMID- 16462336
TI  - Sagittal craniosynostosis: surgical outcomes and long-term growth.
AB  - BACKGROUND: Numerous publications have examined technique-specific results in
      treating sagittal synostosis, but there are scant data examining long-term
      outcomes. This retrospective study was designed to evaluate a large series of
      surgically repaired children with sagittal craniosynostosis and to examine long
      term cranial growth following correction. METHODS: From 1990 to 2003, 132
      children with sagittal synostosis were evaluated and 89 surgically treated
      (single-stage posterior remodeling) patients were retrospectively reviewed (43
      were excluded for multisutural involvement, incomplete records, or nonsurgical
      treatment). Long-term growth was assessed from anthropologic measurements taken
      from 3 to 11 years postoperatively (mean, 4.7 years). RESULTS: The surgical age
      ranged from 2 months to 5 years (mean, 8 months), and the hospital stay was less
      than 3 days. There were no deaths, major complications, infections, or repeated
      remodeling procedures performed. Postoperatively, the cephalic index was
      overcorrected. Subsequent growth of the cranial breadth and length was less than
      predicted. Moreover, growth was more deficient in cranial breadth than length,
      resulting in a regression of the cephalic index over time (p < 0.01). Frontal
      breadth improved immediately postoperatively but did not subsequently narrow over
      time. Head circumference also showed a statistically significant diminished
      capacity for growth (p < 0.001). CONCLUSIONS: This study demonstrated abnormal
      skull growth in children following the surgical correction of scaphocephaly. On
      the basis of these findings, surgeons treating sagittal synostosis may wish to
      expand their goals of treatment beyond normalization to an overcorrection of the
      abnormal skull shape.

PMID- 16462337
TI  - Orbital morphology in exophthalmos and exorbitism.
AB  - BACKGROUND: Exophthalmos is a protrusion of the eyeball due to an increase in
      orbital contents in a normal bony orbit. Exorbitism is a protrusion of the
      eyeball due to a decrease in capacity of the orbital container, with a normal
      orbital content volume such as seen in a congenital form termed nonsyndromic
      exorbitism. High myopia can enhance proptosis. The purpose of this study was to
      provide values for orbital measurements from computed tomography and to suggest
      computed tomography criteria for nonsyndromic exorbitism. METHODS: Seventy-three
      computed tomography scans were collected (57 of Graves' ophthalmopathy and 16 of
      nonsyndromic exorbitism). Thirty-two scans from nonproptotic patients constituted
      a control series. Nine measurements and two indexes, performed on a reference
      axial computed tomography slice transecting the neuro-ocular plane, were obtained
      from each scan. RESULTS: The angle between the sagittal axis and the lateral
      orbital wall, as well as the width of the ethmoid bone (midinterorbital
      distance), was found to be more open in the nonsyndromic exorbitism population. A
      lateral orbital wall angle greater than or equal to 42 degrees and a
      midinterorbital distance greater than 30 mm were chosen as cutpoints. The
      association of these two criteria allowed the authors to obtain a sensitivity of
      62 percent, a specificity of 78 percent, a positive predictive value of 80
      percent, and a negative predictive value of 86 percent for nonsyndromic
      exorbitism. CONCLUSIONS: The different mechanisms of globe protrusion have to be
      taken into account before an orbital expansion/decompression procedure is
      planned. Only a preoperative morphological analysis of the orbital shape permits
      a precise analysis of the relative position of the ocular globe and orbital
      structures, in addition to clinical examination.

PMID- 16462339
TI  - Surgical strategy in the treatment of globe protrusion depending on its mechanism
      (Graves' disease, nonsyndromic exorbitism, or high myopia).
AB  - BACKGROUND: Graves' ophthalmopathy affects orbital contents and eyelids.
      Protrusion of the globe can also be the result of myopia and/or an abnormal orbit
      shape, which is responsible for nonsyndromic exorbitism. It is necessary to
      recognize these components of protrusion to treat patients adequately. The
      authors present a surgical strategy for treatment of the orbit and lids. METHODS:
      Files of 84 patients treated from 1984 to 2003 were retrospectively reviewed.
      Sixty-eight patients were operated on for Graves' ophthalmopathy and 16 for
      nonsyndromic exorbitism with or without myopia. The surgical strategy was adapted
      to the degree of emergency, the age of the patient, and the shape of the orbit
      measured using computed tomography. The accepted standard of treatment was a
      coronal approach with a two-wall expansion, with or without bone grafts,
      especially in cases of associated nonsyndromic exorbitism, with or without
      complementary ablation of the external part of the orbital floor. Lid surgery was
      performed at a second stage. RESULTS: Nonsyndromic exorbitism patients were
      successfully treated in one step. No diplopia was present either preoperatively
      or postoperatively. In contrast, the treatment of the Graves' ophthalmopathy
      patients justified one to three orbital expansion procedures per patient and/or
      one to seven procedures for levator palpebrae lengthening or reinsertion. Forty
      three percent of preexisting diplopias were improved by the surgery. The overall
      postoperative incidence of de novo diplopia was 19 percent. In the Graves'
      ophthalmopathy series, three patients (5 percent) finally underwent strabismus
      surgery. No major complication occurred. CONCLUSIONS: The treatment of Graves'
      ophthalmopathy is challenging. A graded approach is justified. Patients have to
      be informed that several procedures may be necessary and, in cases of
      nonsyndromic exorbitism or myopia, that facial modifications might occur.

PMID- 16462340
TI  - Individual CAD/CAM fabricated glass-bioceramic implants in reconstructive surgery
      of the bony orbital floor.
AB  - BACKGROUND: The aim of the study was to present a set of preliminary cases from
      an ongoing program of reconstructive procedures using a new technique in the
      treatment of severe enophthalmos and diplopia after the primary treatment of
      orbital floor fractures had rendered insufficient results. METHODS: Glass
      bioceramic implants were shaped from computed tomography coordinates with
      computer-assisted design and computer-assisted manufacturing. In this
      prefabrication process, the implants were milled individually out of a solid
      block of Bioverit II (3di Gmbh, Jena, Germany). The adequacy of this
      reconstruction for treating malfunction and aesthetic deficits was evaluated.
      RESULTS: Eight patients with orbital floor fractures underwent successful
      surgery. The results were encouraging, with all patients showing a good
      functional and aesthetic outcome. CONCLUSIONS: Computer-assisted design/computer
      assisted manufacturing implants made of Bioverit II can be used for a very
      accurate and successful secondary reconstruction of the orbital floor. However,
      it addresses only a few aspects of the treatment of orbital floor fractures and
      should be considered as an equal alternative to other reconstruction methods.

PMID- 16462341
TI  - Is there a need for autogenous blood donation in orthognathic surgery?
AB  - BACKGROUND: The present study sought to determine the frequency of blood
      transfusion and to evaluate the need for autogenous blood donations in patients
      undergoing bimaxillary orthognathic surgery. METHODS: According to an inclusion
      and exclusion protocol, 65 patients were selected for further analysis. Twenty
      six patients donated a total of 45 units of autogenous blood; the remaining 39
      patients did not. Medical records were reviewed retrospectively. RESULTS: Donors
      tended to have lower preoperative, intraoperative, and postoperative hemoglobin
      values, as well as lower hematocrit and leukocyte counts. Only the difference in
      mean preoperative leukocyte count, however, was statistically significant (donor:
      6500/microl versus nondonor: 7400/microl; p = 0.021). The rate of transfusion was
      2.5 percent for nondonors and 13 percent for donors of autogenous blood. Six
      donors had to be transfused a total of 8 units of autogenous blood, whereas only
      one of 39 nondonors received an allogenic blood transfusion. This difference
      turned out to be significant according to Fisher's exact test (p = 0.013). None
      of the donors received allogenic blood transfusion. CONCLUSIONS: In the authors'
      analysis, preoperative autogenous blood donation appears to be effective in
      reducing exposure to allogenic blood. Donors of autogenous blood, however, were
      transfused significantly more often than nondonors were. Neither intraoperative
      blood loss nor hematological values justify a preoperative donation of autogenous
      blood on a regular basis.

PMID- 16462342
TI  - Indications and limitations in resorbable P(L70/30DL)LA osteosyntheses of
      displaced mandibular fractures in 4.5-year follow-up.
AB  - BACKGROUND: This study evaluates prospective 4.5-year follow-up of available
      poly(l-lactide-co-dl-lactide) [P(L70/30DL)LA] resorbable plate osteosyntheses in
      displaced traumatic and pathological mandibular fractures. METHODS: P(L70/30DL)LA
      miniplates and screws were used to fixate 50 displaced fractures in 30 patients,
      aged 1 to 83 years, with their informed consent. There were 15 traumatic
      paramedian, seven corpus, 11 angle, and 10 condyle fractures, and seven
      pathological fractures due to atrophy, osteomyelitis, or third molar osteotomy.
      Double osteosyntheses were preferred, with one monocortical plate at the
      dentoalveolar basis (6-mm screws) and a second plate at the inferior margin (8-mm
      screws). RESULTS: The average follow-up was 31 months (range, 6 to 53 months).
      Fifteen (100 percent) traumatic paramedian, seven (100 percent) corpus, 10 (91
      percent) angle, 10 (100 percent) condylar, and three (43 percent) pathological
      fractures healed primarily. Two mandibular angle fractures, traumatic and
      pathological, each initially healed, but 6 weeks postoperatively the first
      fracture re-dislocated on removal of a dental impression by the family dentist,
      and the second re-dislocated after mastication of hard food. One atrophic corpus
      fracture developed a rigid fibrous union in an 83-year-old patient; a preexistent
      osteomyelitis and fracture progressed to further bone loss and finally required
      preformed fibula reconstruction. CONCLUSIONS: Use of the tested resorbable plates
      can be encouraged in multiple displaced mandibular fractures in children and
      likewise in highly compliant dentate adolescents and adults with doubled
      osteosyntheses; traumatic mandibular angle and pathological fractures, however,
      remain critical for nonunion. These necessitate evaluation with future smaller,
      more rigid, and, it is hoped, more economical fixations.

PMID- 16462344
TI  - A virtual reality tracking system for distal mandible movement during distraction
      osteogenesis.

PMID- 16462346
TI  - Functional upgrading of partially recovered facial palsy by cross-face nerve
      grafting with distal end-to-side neurorrhaphy.
AB  - BACKGROUND: Cross-face nerve grafting combined with functional muscle
      transplantation has become the standard in reconstructing an emotionally
      controlled smile in complete irreversible facial palsy. A special problem exists
      in incomplete or partially recovered facial palsies, when the little existing
      function should be preserved but the existing function alone is clinically
      insufficient. METHODS: In this situation, cross-face nerve grafting performed by
      means of end-to-end coaptation to a zygomatic branch of the healthy side and by
      end-to-side neurorrhaphy to a corresponding branch of the incompletely paralyzed
      side is proposed to upgrade smile function on the latter side and contribute to
      more static and dynamic overall symmetry. The interposition nerve graft is set in
      overlength to preserve the possibility of a later muscle transplantation in case
      of unsatisfying functional result through the additional neuronal input. The
      authors have used this concept in seven patients with irreversible partial facial
      palsy. Three cases have a sufficiently long follow-up to be presented here.
      Outcome was objectively quantified with three-dimensional video analysis of
      facial movements. RESULTS: In all three cases, functional improvement and a
      positive effect on the static and dynamic symmetry of the face could be measured.
      None of the patients was disappointed by the smile function achieved or wanted to
      undergo additional muscle transplantation. CONCLUSION: On the basis of these
      first clinical experiences, the authors recommend cross-face nerve grafting with
      overlength and a distal end-to-side neurorrhaphy in patients with irreversible
      incomplete facial palsy affecting the smile.

PMID- 16462348
TI  - Suprascapular nerve reconstruction in 118 cases of adult posttraumatic brachial
      plexus.
AB  - BACKGROUND: Shoulder stabilization is of utmost importance in upper extremity
      reanimation following paralysis from devastating brachial plexus injuries. The
      purpose of this report is to present the authors' experience with suprascapular
      nerve reconstruction in 118 cases of adult brachial plexus lesions. Outcomes were
      analyzed in relation to various factors, including patient age, denervation time,
      donor nerve used, and functional restoration achieved in the supraspinatus versus
      the infraspinatus muscles. METHODS: The medical records of 118 adult patients
      operated on by a single surgeon between 1978 and 2002 who had suprascapular nerve
      reconstruction were reviewed; 102 patients had adequate follow-up. Direct
      neurotization of the suprascapular nerve was carried out in 78 patients, while in
      40 patients, interposition nerve grafts were used. In 80 patients, the distal
      spinal accessory was used as the motor donor nerve for suprascapular nerve
      neurotization, while in 10 patients, other extraplexus motor donors were used. In
      28 patients, intraplexus motor donors were used to reinnervate the suprascapular
      nerve. RESULTS: Results were good or excellent in 79 percent of the patients for
      the supraspinatus muscle and in 55 percent for the infraspinatus. There was a
      statistically significant difference between direct spinal accessory to
      suprascapular nerve neurotization and accessory to suprascapular via a nerve
      graft. Early surgery and less than 6 months of denervation time yielded
      significantly better results than late surgery and more than 6 months of delay in
      the treatment. CONCLUSIONS: Suprascapular nerve neurotization is a high priority
      in upper limb reanimation for restoration of glenohumeral joint stability,
      shoulder abduction, and external rotation. Concomitant neurotization of the
      axillary nerve yields improved outcomes in shoulder abduction function. The best
      results are seen when direct neurotization of the suprascapular nerve is
      performed within 6 months from the injury.

PMID- 16462349
TI  - Incidence and characteristics of hospitalized patients with pressure ulcers:
      State of Washington, 1987 to 2000.
AB  - BACKGROUND: Pressure ulcers complicate the hospital course of critically injured
      or ill patients. Guidelines have been promulgated to prevent pressure ulcers in
      hospitalized patients. The purpose of this study was to determine whether these
      guidelines have, in fact, reduced the incidence of pressure sores. METHODS: The
      authors examined census data from the National Center for Health Statistics and
      the Washington State Department of Health for the 14-year period 1987 through
      2000 and identified patients with a pressure ulcer listed as the primary
      diagnosis (International Classification of Diseases, Ninth Revision, Clinical
      Modification code 707.0) and patients admitted for other diagnoses with pressure
      ulcer as a secondary diagnosis. The authors reasoned that patients who were
      admitted for treatment of pressure ulcers would have the diagnosis listed as
      primary, whereas those who were admitted for other reasons and developed pressure
      ulcers during the admission would have pressure ulcer listed as a secondary
      diagnosis. Other available data included patient age, sex, procedures for
      pressure ulcers (International Classification of Diseases, Ninth Revision,
      Clinical Modification codes 15920 through 15999), length of stay, and hospital
      charges for care. RESULTS: The incidence of pressure ulcers as a primary
      diagnosis varied from 7.0 to 8.3 per 100,000 population but did not change over
      the 14-year study period. The rate of operation for these ulcers also did not
      change. The incidence of pressure ulcers as either a primary or secondary
      diagnosis doubled from 34.5 to 71.6 per 100,000 (p < 0.001), whereas the
      incidence of operative procedures for these ulcers did not change. CONCLUSION:
      The authors found no evidence that the guidelines for the prevention of pressure
      ulcers have been effective in decreasing pressure ulcer formation, but it may be
      that pressure ulcers are now being reported in a more thorough manner.

PMID- 16462347
TI  - Carbon dioxide laser ablation for treatment of lymphangioma of the conjunctiva.

PMID- 16462350
TI  - 10-year experience with the gracilis myofasciocutaneous flap.

PMID- 16462351
TI  - Posterior tibial artery flap in poliomyelitis patients with lower extremity
      paralysis.
AB  - BACKGROUND: Poliomyelitis is a disease that can render affected individuals
      incapacitated to a variable degree. A normal lifespan is expected and therefore
      the patients deserve every effort at curative cancer resection and
      reconstruction. Those with lower extremity paralysis rely heavily on their upper
      limbs and torso for ambulation; therefore, their compromised limbs may be a
      better donor site for flaps. METHODS: All poliomyelitis patients with lower
      extremity paralysis over a 20-month period who underwent head and neck
      reconstruction were selected for a retrospective review. Perioperative
      complications were noted and outpatient follow-up was performed. RESULTS: Three
      patients underwent reconstruction of defects using the posterior tibial artery
      flap. Two patients required reconstruction of a buccal defect and one patient
      required soft palate reconstruction. All patients healed without complications
      and none required reexploration. At a mean follow-up of 10 months, there was no
      incidence of donor limb vascular compromise, cold intolerance, or long-term
      paresthesias. CONCLUSIONS: The posterior tibial artery free flap has been used
      successfully in the past; however, its popularity has been limited because of
      sacrifice of the posterior tibial artery. Nevertheless, in patients with lower
      extremity paralysis, this flap may fulfill the requirements of a thin, pliable
      flap with minimal hair that has a long pedicle and a reliable blood supply. Most
      importantly, the use of this flap obviates the need to use flaps that fulfill the
      same requirement, such as forearm flaps, that would be taken from patients'
      functioning limbs.

PMID- 16462352
TI  - Therapeutic outcome of hyperbaric oxygen and basic fibroblast growth factor on
      intractable skin ulcer in legs: preliminary report.
AB  - BACKGROUND: Beneficial effects of hyperbaric oxygen on ischemic vascular diseases
      have been noted. Acceleration of wound healing with basic fibroblast growth
      factor has also been reported. The authors employed combination therapy of
      hyperbaric oxygen and basic fibroblast growth factor in patients with skin ulcer
      in legs refractory to conventional therapy. METHODS: Three men and four women
      were simultaneously treated with hyperbaric oxygen at 2 absolute atmospheric
      pressures for 90 minutes daily and spray treatment of basic fibroblast growth
      factor to the ulcer bed daily for an average of 2.6 months. Biopsy specimens
      obtained from ulcer tissues were divided into two pieces, one for histologic
      examination and the other for measuring fibrous protein. RESULTS: Ulcers were
      completely cured in five of seven patients. Two patients showed shrinkage of
      ulcer size. This combined therapy induced proliferation of connective tissue of
      the ulcer tissues, especially collagen and noncollagenous protein. CONCLUSIONS:
      Combined treatment with hyperbaric oxygen and basic fibroblast growth factor may
      be useful in patients with intractable skin ulcers in legs, and the shrinkage
      effect of this therapy is probably related to the proliferation of granulation
      tissues of the ulcer lesion.

PMID- 16462354
TI  - Effect of the Veterans Affairs Medical System on plastic surgery residency
      training.
AB  - BACKGROUND: Teaching hospitals within the Veterans Affairs Health System perform
      the majority of complex and high-risk surgical procedures in the veteran patient
      population. Residency positions in the Veterans Affairs Medical System are
      usually part of a rotational educational system within a university-based
      residency, and plastic surgeons in training are a major work force and health
      care provider. The purpose of this study was to evaluate the current effect of
      the Veterans Affairs Medical System on plastic surgery residency training.
      METHODS: A 6-year (January of 1998 to December of 2003) review was performed of
      procedures completed at the Durham Veterans Affairs Medical Center, Section of
      Plastic Surgery. Procedures were divided into the following categories:
      extremities and trunk; breast and cosmetic; head and neck, including excision of
      skin lesions; hand surgery; craniomaxillofacial surgery; and other. Only
      procedures performed in the main operating room were reviewed and analyzed. In
      addition, a detailed review was performed of major head and neck reconstructions
      with free tissue transfer. RESULTS: A total of 1655 operative procedures were
      performed in 1290 patients. The ratio of men to women was 6:1 (1112 men and 178
      women). Patients ranged in age from 26 to 97 years (average age, 62.7 years).
      Procedures in the extremities and trunk (n = 193, 11.7 percent), breast and
      cosmetic (n = 228, 13.8 percent), hand surgery (n = 155, 9.4 percent), and other
      (n = 275, 16.6 percent) categories were comparably distributed. Although the head
      and neck category accounted for the highest number of procedures (n = 766, 46.3
      percent), the majority of these procedures were simple excisions of skin tumors
      (n = 612). There were significantly fewer major craniomaxillofacial cases (n =
      38, 2.3 percent). CONCLUSIONS: Data from the retrospective analysis reveal that a
      broad spectrum of plastic surgical procedures is performed within the Veterans
      Affairs Health System, serving as a tremendous resource for resident training.
      The fact that approximately 260 procedures per year are performed demonstrates an
      active service. Craniomaxillofacial surgery is currently underrepresented
      compared with other categories at the authors' particular institution. By their
      definition, nonspecific plastic surgical procedures ("other") account for 275
      (16.6 percent) of all 1655 procedures performed. This demonstrates that plastic
      surgery "overlaps" with other specialties, such as dermatology. The Veterans
      Affairs Health System will continue to play a significant role in the future
      training of plastic surgeons. Now, more than ever, a strong Veterans Affairs
      surgical service, including plastic surgery and its modern techniques, will be
      needed.

PMID- 16462355
TI  - Cross-linked hyaluronic acid fillers.

PMID- 16462356
TI  - Silver dressings.

PMID- 16462357
TI  - Patient Safety and Quality Improvement Act of 2005: what you need to know.

PMID- 16462360
TI  - Use of a suture anchor for correction of ectropion in facial paralysis.

PMID- 16462363
TI  - Correction of ectropion in facial paralysis.

PMID- 16462364
TI  - Diced cartilage grafts in cosmetic surgery.

PMID- 16462366
TI  - Timing of otoplasty for prominent ears.

PMID- 16462367
TI  - Subfascial periareolar augmentation mammaplasty.

PMID- 16462369
TI  - Rectus sheath plication in abdominoplasty.

PMID- 16462372
TI  - Plastic surgery Web sites: what is the quality of information currently
      available?

PMID- 16462371
TI  - Distally based lateral supramalleolar adipofascial flap.

PMID- 16462373
TI  - Cutaneous angiosarcoma of the skin: three rare cases.

PMID- 16462375
TI  - Atlanto-axial rotatory fixation following ear surgery for microtia.

PMID- 16462376
TI  - Old is still gold: use of deltopectoral flap for single-stage pharyngeal
      reconstruction.

PMID- 16462377
TI  - Giant pleomorphic lipoma of the neck.

PMID- 16462378
TI  - An unusual entity for a plastic surgeon: Madelung syndrome.

PMID- 16462379
TI  - Osteosynthesis for open rhinoplasty of the hump nose.

PMID- 16462380
TI  - Composite resection of the skin, orbicularis oculi, and retro-orbicularis oculi
      fat in upper eyelid blepharoplasty.

PMID- 16462381
TI  - Patient grounded after face lift.

PMID- 16462382
TI  - A potential complication with an extraoral distractor for mandible lengthening:
      facial nerve paralysis.

PMID- 16462383
TI  - Exact determination of maxillofacial fracture lines with a hypodermic dental
      needle: a practical technique.

PMID- 16462384
TI  - Untreated median cleft of the lower lip in advanced age.

PMID- 16462385
TI  - Innovative tailoring of the composite flap in breast reconstruction using
      templates.

PMID- 16462386
TI  - Lactation, galactorrhea, and timing of reduction mammaplasty.

PMID- 16462387
TI  - The role of subdermal suspension threads in elevation of the inframammary folds.

PMID- 16462388
TI  - A new use for the Cusco speculum.

PMID- 16462389
TI  - Spontaneous rupture of internal mammary artery.

PMID- 16462390
TI  - Mixed-thickness burn due to infrared massaging device.

PMID- 16462391
TI  - Triple intercalated flaps in perineal urethral replacement: an efficient
      technique to prevent circumferential urethral stenosis.

PMID- 16462392
TI  - The need for aggressive follow-up after cultured epidermal autograft-grafted full
      thickness burn.

PMID- 16462393
TI  - Lymphatic mapping and sentinel lymph node biopsy for staging of aggressive
      digital papillary adenocarcinoma.

PMID- 16462394
TI  - A subungual schwannoma.

PMID- 16462395
TI  - Long-term effects of amniotic bands not treated at an early age.

PMID- 16462396
TI  - Angiomyomatous hamartoma of inguinal lymph nodes.

PMID- 16462397
TI  - Tattoos masquerading as full-thickness burns: limitations of laser Doppler burns
      assessment.

PMID- 16462398
TI  - A new material for the standard burn model: Allevyn adhesive.

PMID- 16462399
TI  - Adhesive bands to prevent fogging of lenses and glasses of surgical loupes or
      microscopes.

PMID- 16462400
TI  - The syringe Guedel.

PMID- 16462401
TI  - Now toward a board-certified leadership.

PMID- 16462402
TI  - A new treatment for injuries to the anterior cranial fossa after rhinoplasty.

PMID- 16462404
TI  - Increasing survival with HIV: impact on nursing care.
AB  - The introduction of highly active antiretroviral therapy (HAART) has transformed
      human immunodeficiency virus (HIV) infection from a rapidly progressive
      catastrophic illness to a chronic condition. Individuals with HIV are living
      longer and developing conditions usually associated with aging, as well as
      complications from pre-existing or subsequently acquired conditions. In addition,
      toxicities associated with HAART may precipitate or exacerbate comorbid
      conditions. As opportunistic infections account for fewer admission and lower
      mortality rates, new patterns of illness are emerging. Complex interactions among
      multiple, sometimes overlapping conditions require focused yet comprehensive
      attention in care and management. Nurses will encounter HIV-infected patients in
      an increasing range of care settings, and an understanding of the range and
      interaction of potential comorbidities and their treatments with HIV and its
      treatment will be required to provide safe and effective care.

PMID- 16462405
TI  - HAART to heart: HIV-related cardiomyopathy and other cardiovascular
      complications.
AB  - More than one million Americans have been diagnosed with human immunodeficiency
      virus (HIV). Advances in prevention and treatment of HIV have led to an increased
      life expectancy for patients with HIV infection. Due to their increased life
      span, HIV+ patients are now presenting to hospitals with an increased number of
      diverse late-stage complications, such as cardiomyopathy and other cardiovascular
      conditions. These complications are as a direct or indirect result of HIV
      disease, HIV treatment modalities, comorbid conditions, dietary and lifestyle
      factors, and unknown etiologies. Cardiac complications, particularly HIV-related
      dilated cardiomyopathy, are potentially life-threatening diagnoses, with symptoms
      that may be minimized with appropriate cardiac-specific assessments and
      treatments, patient teaching, and collaboration among nurses caring for the HIV
      positive client with cardiac disease.

PMID- 16462406
TI  - HIV peripheral neuropathy: pathophysiology and clinical implications.
AB  - One of the most debilitating neurological complications of human immunodeficiency
      virus (HIV), affecting nearly one in three patients, is painful peripheral
      neuropathy. Although HIV infection can cause distal sensory polyneuropathy (DSP),
      the advent of highly active antiretroviral therapy (HAART) to treat HIV infection
      has resulted in a significant number of patients developing a clinically
      indistinguishable form of toxic neuropathy. The predominant symptom, regardless
      of etiology, is excruciating unremitting pain, resistant to pharmacological
      treatments, that leads to a reduction in the ability to conduct activities of
      daily living and, eventually, inability to ambulate. Since withdrawal from
      nucleoside therapy is not typically recommended, a more thorough understanding of
      the etiology and pathophysiology underlying nucleoside-induced peripheral
      neuropathy, through basic and clinical research endeavors, will aid in the
      development of new therapeutic treatments aimed at alleviating or ameliorating
      pain. This article provides the latest information regarding the pathophysiology
      and clinical implications of HIV peripheral neuropathy.

PMID- 16462408
TI  - The hypothalamic-pituitary-adrenal axis in critical illness.
AB  - Severe stress, associated with critical illness, activates the hypothalamic-
      pituitary-adrenal (HPA) axis and stimulates the release of cortisol from the
      adrenal cortex. Cortisol is essential for general adaptation to stress and plays
      a crucial role in cardiovascular, metabolic, and immunologic homeostasis. During
      critical illness, prolonged activation of the HPA axis can result in
      hypercortisolemia and hypocortisolemia; both can be detrimental to recovery from
      critical illness. Recognition of adrenal dysfunction in critically ill patients
      is difficult because a reliable history is not available and laboratory results
      are difficult to interpret. The review in this article will illustrate how
      adrenal dysfunction presents in critically ill patients and how appropriate
      diagnosis and management can be achieved in the critical care setting.

PMID- 16462410
TI  - Management of hyperglycemic emergencies.
AB  - The prevalence of diabetes mellitus makes the occurrence of hyperglycemic
      emergencies a key component in clinical practice. The expert nurse is well
      positioned to manage both diabetic ketoacidosis and hyperosmolar hyperglycemic
      states. Patient care management includes a high index of suspicion for awareness
      for the possibility of diabetic ketoacidosis or hyperosmolar hyperglycemic states
      in patients based on a multifactorial etiology, evidence-based treatment of the
      emergent episode, and tertiary prevention to prevent recurrent episodes.

PMID- 16462409
TI  - Hyperglycemia in the critically ill patient.
AB  - Hyperglycemia and insulin resistance are common among critically ill patients and
      occur in patients with or without a history of diabetes mellitus. All patients
      undergoing critical illness are at risk for stress-induced hyperglycemia. Some
      patients may be at greater risk for hyperglycemia than others when considering
      underlying disease states and iatrogenic factors. Many recent studies demonstrate
      that tight glucose control can decrease morbidity and mortality associated with
      critical illness. This article reviews the pathophysiology behind stress-induced
      hyperglycemia, the evidence to support tight glycemic control, and the importance
      of an intensive insulin therapy protocol to standardize treatment among critical
      care patients.

PMID- 16462411
TI  - Endocrine problems in critically ill children: an overview.
AB  - The endocrine system maintains a delicate balance of physiologic processes
      including growth and sexual maturation, energy production and utilization, fluid
      and electrolyte balance, and circulatory function. Although endocrine regulation
      of growth and sexual maturation is a significant issue in general pediatrics,
      disorders of energy production and utilization, fluid and electrolyte balance,
      and circulatory function are the endocrine causes of critical illness in
      children. Care of the child with critical endocrine disease requires an
      understanding of endocrine pathophysiology, keen history taking and assessment
      skills, and knowledge of the pharmacology of synthetic hormone treatment. This
      article will provide an overview of common endocrine problems encountered in
      critically ill children with attention to endocrine problems that are unique to
      pediatrics and that may pose diagnostic and treatment dilemmas for healthcare
      providers without experience or education in pediatric critical care.

PMID- 16462417
TI  - The Classic: Osteoporosis. 1956.

PMID- 16462412
TI  - Metabolic syndrome in the acute care setting.
AB  - The metabolic syndrome is a clinical condition that is a powerful predictor for
      cardiovascular morbidity and mortality. Hypertension, abdominal obesity, high
      blood glucose levels, and abnormal blood lipid levels characterize metabolic
      syndrome. Therapeutic treatment of the metabolic syndrome confers a significant
      risk reduction for both type 2 diabetes and premature cardiovascular events. In
      the hospital setting, the management of hyperglycemia, one of the clinical
      components of the metabolic syndrome, has been secondary in importance to the
      condition that prompted admission. Hyperglycemia in the hospitalized patient has
      been associated with increased lengths of stay, higher rates of hospital-acquired
      infections, and increased mortality. Early recognition and treatment of
      hyperglycemia and the associated metabolic components that comprise the metabolic
      syndrome may reduce morbidity and mortality in the hospital setting. More
      aggressive interventions will aid in reducing costs while simultaneously
      improving patient care and safety.

PMID- 16462419
TI  - The Classic: An account of the bones of animals being changed to a red colour by
      aliment only. 1966.

PMID- 16462420
TI  - The Classic: Quantitative computed tomography of vertebral spongiosa: a sensitive
      method for detecting early bone loss after oophorectomy. 1982.

PMID- 16462421
TI  - Burden of osteoporosis.
AB  - The number of the people with osteoporosis increases as the population ages.
      Increasing numbers of patients with osteoporotic fractures may have a serious
      economic impact on society and on the quality of life of the patient. We review
      some literature and provide expert opinion on the burden of osteoporosis.
      Awareness among clinicians and health care professionals on osteoporosis should
      be increased to overcome the burden of the disease. Although most of the
      osteoporotic fractures are treated by orthopaedic surgeons, many patients with
      these problems are not diagnosed appropriately and treated for probable
      osteoporosis. Appropriate diagnosis of the disease is essential to prevent
      osteoporotic fractures and related mortality and morbidity. Indirect costs and
      sociologic and psychological impact of fractures should be evaluated together
      with the direct costs of the disease. LEVEL OF EVIDENCE: Economic and decision
      analysis, level V (expert opinion). See the Guidelines for Authors for a complete
      description of the levels of evidence.

PMID- 16462422
TI  - Etiology of senile osteoporosis: a hypothesis.
AB  - Osteoporosis is a major health problem characterized by compromised bone strength
      predisposing patients to an increased risk of fracture. It may cause morbidity
      and mortality in elderly men and women. The etiologic factors that lead to senile
      osteoporosis still are unclear. Based on the available experimental and clinical
      evidence, we update our earlier proposal that zinc deficiency plays a role in the
      pathogenesis of senile osteoporosis. However, the mechanism of zinc deficiency in
      osteoporosis remains unclear. Zinc deficiency may lead to the increase of
      endogenous heparin probably causing degranulation of mast cells and release of
      endogenous heparin, and an increase in the bone-resorbing effect of prostaglandin
      E2. Endogenous heparin and prostaglandin E2 are probably cofactors of parathyroid
      hormone and may have a role in the pathogenesis of senile osteoporosis enhancing
      the action of parathyroid hormone. Therefore, zinc replacement by dietary zinc
      supplementation might be valuable to prevent or treat senile osteoporosis.
      Additional studies are necessary for the evaluation of the possible role of zinc
      in the etiology of senile osteoporosis. LEVEL OF EVIDENCE: Level V (expert
      opinion). See the Guidelines for Authors for a complete description of the levels
      of evidence.

PMID- 16462424
TI  - Glucocorticoid-induced osteoporosis and its treatment.
AB  - Osteoporosis and fractures are frequent and important consequences of
      glucocorticoid therapy. Many factors contribute to bone loss during
      glucocorticoid therapy, such as underlying disease, malnutrition, vitamin D
      insufficiency, hypogonadism, and low body weight. Bone loss occurs particularly
      in the first few months of glucocorticoid treatment and affects more cancellous
      than cortical bone, with reduced bone formation and increased bone resorption.
      The risk of fracture increases rapidly in patients with glucocorticoid therapy.
      The existence of a threshold is not well defined but the risk of fracture is
      increased in patients with higher doses of glucocorticoids. Other effects include
      altered production of gonadal sex hormones, inhibition of intestinal calcium
      absorption, and enhancement of renal excretion of calcium. Prevention of
      glucocorticoid-induced osteoporosis is based on general measures such as calcium
      and vitamin D supplementation, adequate protein intake, regular physical
      exercise, and specific therapies. Bisphosphonates, which are potent bone
      resorption inhibitors, have been shown to increase bone mineral density and to
      decrease fracture risk, so that they represent the first choice in the prevention
      of glucocorticoid-induced osteoporosis. Glucocorticoid-induced osteoporosis is a
      major burden to those whom it affects. It can be prevented provided efficacious
      preventive measures are introduced early during glucocorticoid treatment. LEVEL
      OF EVIDENCE: Level V (expert opinion). See the Guidelines for Authors for a
      complete description of the levels of evidence.

PMID- 16462425
TI  - Raloxifene reduces fractures in postmenopausal women with osteoporosis.
AB  - Recently, selective estrogen receptor modulators have been developed for the
      management of osteoporosis based on antiosteoclastic properties similar to that
      of estrogens but with a safety profile including potential benefits on the
      breast, heart, and cognitive function. Raloxifene, the first selective estrogen
      receptor modulator to be marketed for the treatment of osteoporosis has shown
      reduction in spinal fracture risk in patients with low bone mineral density with
      (48%) or without (35%) prevalent vertebral fracture. Raloxifene also reduces
      nonvertebral fractures in high risk patients (47%). The decrease in Type I
      procollagen N-terminal propeptide at 1 year accounts for 28% of the total
      reduction in vertebral fracture risk. Raloxifene reduced the risk of estrogen
      receptor-positive invasive breast cancer by 84%. Among subjects with increased
      cardiovascular risk at baseline, those assigned to raloxifene had a 40% decrease
      in the risk of cardiovascular events compared with placebo. The definite anti
      fracture efficacy of raloxifene at the spine, its plausible effect on non-spine
      fracture in high-risk patients and its beneficial effect on breast and heart make
      this compound an interesting approach for women presenting with osteoporosis.
      LEVEL OF EVIDENCE: Therapeutic study, level II (lesser quality randomized
      controlled trial [eg, < 80% followup, no blinding, or improper randomization]).
      See the Guidelines for Authors for a complete description of the levels of
      evidence.

PMID- 16462423
TI  - Mineral changes in osteoporosis: a review.
AB  - Bone mineral composition, crystallinity, and bone mineral content of osteoporotic
      patients are different from those of normal subjects. We review the evidence that
      these mineralization parameters contribute to the strength (fracture resistance)
      of bone and the methods that have been used to examine them. A specific example
      is provided from analysis of biopsies from the Multiple Outcomes in Raloxifene
      Evaluation trial. For the analyses, randomly selected biopsies from placebo, low
      dose, and high-dose groups (n = 5 per group) obtained at time zero and 2 years
      after treatment were examined by infrared imaging spectroscopy. In all cases,
      comparable increases in mineral content were found, but there were no significant
      variations in mineral crystallinity.

PMID- 16462427
TI  - Long-term outcome of weekly bisphosphonates.
AB  - Bisphosphonates currently are the preferred therapy for treating osteoporosis.
      Treatment with potent bisphosphonates such as alendronate or risedronate
      decreases biochemical markers of bone turnover and increases bone mineral
      density. These changes are associated with significant reductions in vertebral
      and nonvertebral fracture risk. Clinical trial data with up to 10 years of
      followup shows these agents are effective and well tolerated for long-term
      periods. Daily administration is effective and generally well tolerated. However,
      once weekly doses are more convenient, which may enhance long-term compliance and
      lead to more successful outcomes. The pharmacokinetics and mechanism of action
      predict the short-term and long-term skeletal effects and safety profile of once
      weekly doses of bisphosphonates are similar to daily doses. These predictions are
      supported by authors of trials of up to 2 years who report once-weekly doses are
      therapeutically equivalent to daily doses in terms of BMD and biochemical markers
      of bone remodeling. Once-weekly bisphosphonate doses have safety and tolerability
      profiles as good as daily doses and are comparable with the placebo. LEVEL OF
      EVIDENCE: Therapeutic study, Level V (expert opinion). See the Guidelines for
      Authors for a complete description of the levels of evidence.

PMID- 16462428
TI  - Trunk muscle strength is a strong predictor of bone loss in postmenopausal women.
AB  - To clarify whether trunk muscle strength and self-reported exercise habits
      predict subsequent bone loss in healthy post- menopausal women, we examined 143
      community-dwelling ambulatory postmenopausal Japanese women (age: 59.9 +/- 6.5
      years) without any diseases affecting bone metabolism at baseline, and followed
      109 of the 143 subjects for 4 years. Bone mineral density at baseline and at
      followup was measured at the spine by DEXA to determine the annual change in bone
      mineral density during the followup. Subjects who lost bone mineral density at an
      annual rate exceeding -1.78% (1 standard deviation below the mean rate) were
      defined as rapid bone losers. The isokinetic concentric and eccentric peak
      torques of the trunk flexors and extensors were measured at baseline. The
      exercise habits of the subjects were evaluated through detailed interviews. The
      eccentric trunk flexor and extensor torques were found to correlate with a
      positive dose-dependent effect on change in bone mineral density while exercise
      habits showed no correlation. The lower tertile group for the extensor torque
      showed a ten-fold greater risk for rapid bone loss compared with the upper
      tertile group. Postmenopausal women with decreased trunk muscle torque may be at
      increased risk for osteoporosis and should be a target group for preventive
      measures. LEVEL OF EVIDENCE: Prognostic study, level II (prospective study). See
      the Guidelines for Authors for a complete description of the levels of evidence.

PMID- 16462426
TI  - Strontium ranelate: the first dual acting treatment for postmenopausal
      osteoporosis.
AB  - Currently available medications, such as bisphosphonates, selective estrogen
      receptor modulators, and teriparatides, have shown their ability to reduce
      vertebral and/or nonvertebral fractures. Questions remain regarding their long
      term innocuousness and several studies showed that adhering to currently marketed
      anti-osteoporotic medications remain sub-optimal. There is, therefore, an urgent
      need for the development of new effective, safe, and user-friendly medications to
      optimize the treatment of postmenopausal osteoporosis. The current review was
      designed to assess, through an extensive literature search, the antifracture
      efficacy of strontium ranelate on the axial and appendicular skeleton. Two
      multinational Phase 3 clinical trials have shown its efficacy and safety in the
      treatment of postmenopausal osteoporosis. In the Spinal Osteoporosis Therapeutic
      Intervention trial, strontium ranelate (2 g/day) treatment reduced the relative
      risk of a new vertebral fracture by 41% after 3 years compared with placebo. Data
      from the Treatment of Peripheral Osteoporosis study showed a 16% reduction in the
      relative risk of nonvertebral fracture in all patients and a 36% reduction in hip
      fracture in high-risk patients. Strontium rane-late reduces the risk of all
      fragility fractures and is well tolerated, which makes it a new first-line
      alternative in the treatment of postmenopausal osteoporosis. LEVEL OF EVIDENCE:
      Therapeutic study, Level II (lesser quality randomized controlled trial [eg, <
      80% followup, no blinding, or improper randomization]). See the Guidelines for
      Authors for a complete description of the levels of evidence.

PMID- 16462429
TI  - Beta-blockers increase bone mineral density.
AB  - Authors of animal studies suggest that beta-blockers stimulate bone formation and
      inhibit bone resorption. On the other hand, data in humans are limited and
      conflicting results exist in literature. We conducted a prospective case-control
      study in order to investigate the effects of beta-blockers on bone mineral
      density in the elderly population. None of the patients were receiving anti
      resorptive medicine. Bone mineral density of 50 beta-blocker users was
      significantly greater at all measured skeletal sites compared with 100 nonusers.
      Bone mineral density for total hip and spine (beta-blocker users and nonusers)
      were, 0.85 +/- 0.13, 0.80 +/- 0.11 and 0.90 +/- 0.15, 0.83 +/- 0.12,
      respectively. Our results suggest that use of beta-blockers is associated with an
      increase in bone mineral density. LEVEL OF EVIDENCE: Therapeutic study, LEVEL III
      (case control study). See the Guidelines for Authors for a complete description
      of the levels of evidence.

PMID- 16462430
TI  - Correction of osteoporotic fracture deformities with global sagittal imbalance.
AB  - Osteoporotic spinal deformities with global sagittal imbalance have devastating
      effects on patients. However, treatment is difficult and there is a high risk of
      perioperative medical and mechanical complications. Patients with osteoporotic
      spinal deformities are not ideal candidates for posterior pedicle subtraction
      osteotomy; the condition necessitates combined anterior-posterior for corrections
      of the deformity. We ascertained the complication rates and efficacy of the
      anterior-posterior surgery and determined the factors influencing the results. To
      determine complication rates we analyzed a series of patients (n = 32). To
      evaluate overall results, we analyzed 18 patients with more than 2-years
      followup. A total of 18 complications occurred in 12 of 32 patients (37.5%) with
      seven early complications occurring in five patients and 11 delayed complications
      occurring in seven patients. Three patients needed additional surgery to treat
      the complications. At 2 years postoperatively, 17 of 18 patients (94%) reported
      subjective improvement with 54% decrement of Oswestry Disability Index and 70%
      decrement of the visual analogue scale pain score. The factors associated with
      clinical improvement was restoration of total lumbopelvic lordosis, C7 plumb, and
      control of T4-12 thoracic kyphosis. Prevention and aggressive treatment of
      junctional fractures were important in achieving favorable results. LEVEL OF
      EVIDENCE: Therapeutic study, Level IV (case series, [patients treated one way
      with no comparison group of patients treated in another way]). See the Guidelines
      for Authors for a complete description of the levels of evidence.

PMID- 16462431
TI  - Vibration analysis of the human radius of elderly men.
AB  - Vibration analysis seldom has been used in detecting structural and mechanical
      changes in physiologic and pathologic bone conditions. We sought to correlate
      natural frequency of the radius measured by vibration analyses with bone mineral
      density measured by dual-energy xray absorptiometry and quantitative computed
      tomography (including cortical thickness). Sixty sedentary men between 50 and 70
      years old were deemed osteopenic or healthy. A higher natural frequency of the
      dominant and nondominant radius was seen in the healthy men compared with the
      osteopenic men. Natural frequency was consistent with bone mineral density in
      dominant and nondominant radius in both groups. Moreover, there was a correlation
      between bone mineral density measured by dual-energy xray absorptiometry and
      natural frequency in the dominant and nondominant radius. Cortical thickness of
      the dominant and nondominant radius also correlated with natural frequency. We
      concluded natural frequency measured by vibration analysis is a precise method
      for the assessment of structural properties of bone and correlates with the bone
      mineral density of the radius. LEVEL OF EVIDENCE: Diagnostic study, Level II
      (Testing of previously developed diagnostic criteria on consecutive patients
      [with universally applied reference "gold" standard]). See the Guidelines for
      Authors for a complete description of the levels of evidence.

PMID- 16462433
TI  - Quantitative computed tomography BMD reference values in women of Izmir, Turkey.
AB  - In quantitative computed tomography applications for the diagnosis of
      osteoporosis, the bone mineral density value obtained has to be compared with a
      reference data. This data is influenced by several factors including sex, age,
      and ethnicity. Therefore, reference data that accurately represent the population
      at large is essential. We established age-based quantitative computed tomography
      bone mineral density reference values for healthy women residing in Izmir,
      Turkey. We recruited 396 healthy women from 20 to 83 years old (mean age, 51.08
      years). Quantitative computed tomography bone mineral density measurements were
      performed using the GE 9800 Highlight Advantage scanner at the L1, L2, and L3
      lumbar vertebrae. The mean bone mineral density (mg/cm) +/- standard deviation of
      the normal reference group of women from 20 to 39 years old was 168.86 mmg/cm3 +/
      21.59. The threshold bone mineral density value for osteoporosis at a T score < 
      2.5 was 114.83 mg/cm3. The slope, intercept, and r values at bone mineral density
      versus age linear regression test were -2.44, 251.1, and 0.70, respectively. The
      percentage of annual bone mineral density loss was 1.6%. The bone mineral density
      values of Turkish women were not distinct from most countries' reference values.
      LEVEL OF EVIDENCE: Diagnostic study, Level II (Development of diagnostic criteria
      on consecutive patients [with universally applied reference "gold" standard]).
      See the Guidelines for Authors for a complete description of the levels of
      evidence.

PMID- 16462432
TI  - Do sacrificial bonds affect the viscoelastic and fracture properties of bone?
AB  - Sacrificial bonds have been suggested as a toughening mechanism for bone tissue.
      Ionic bridges formed by divalent calcium ions between collagen molecules have
      been proposed as candidates for sacrificial bonds. If this mechanism is active at
      the macroscopic level, we should observe changes in mechanical properties of bone
      when calcium ions are maintained or removed from the tissue. To test this
      hypothesis, we measured viscoelastic and monotonic mechanical properties of
      cortical bone subjected to differing ionic environments. Storage modulus of bone
      could be changed up to 3.8% by the presence or absence of Na+ or Ca++ in the
      environment in a reversible fashion when bones were monitored continuously during
      treatments. A long-term one-time treatment increased the viscoelastic properties
      of bone soaked in Na+ solutions whereas the viscoelastic properties of bones
      soaked in Ca++ solutions were maintained. However, the strength and toughness of
      bone specimens soaked and fractured in treatment solutions were not improved. The
      presence of Ca++ affected the mechanical behavior of mineralized bone tissue at
      the macro scale. These effects were reversible, consistent with the original
      proposal. However, these effects may not necessarily indicate an increase in
      strength or toughness of the tissue at the macro scale.

PMID- 16462435
TI  - The mechanics of polymethylmethacrylate augmentation.
AB  - Osteoporosis frequently leads to vertebral compression fractures. Percutaneous
      cement augmentation, one recent technique, may alter the biomechanics of the
      vertebral body and spinal segment. These alterations reportedly predispose the
      spinal segment to additional vertebral compression fractures. We investigated the
      changes in segment stiffness and strength after polymethylmethacrylate
      augmentation. Twelve thoracic segments consisting of five vertebral bodies were
      divided into two groups, a pure moment group (Group 1) and an eccentric
      compression group (Group 2). Baseline measurements of stiffness were taken on
      each segment followed by the creation of an initial vertebral compression
      fracture during which stiffness and strength were measured. After augmentation,
      stiffness was again measured. Finally, a second vertebral compression fracture
      was created measuring stiffness and strength again. Augmentation did not alter
      stiffness before and after augmentation in either group. Augmentation also did
      not result in any difference in strength measured at subsequent fracture when
      compared with strength measured at initial fracture in either group. The
      augmentation of vertebral compression fractures by kyphoplasty does not alter the
      stiffness or the strength of the multilevel segments and eccentric compression in
      contrast to pure moments leads to a lower strength during mechanical testing.

PMID- 16462434
TI  - In vitro osteogenic response of rat bone marrow cells to bFGF and BMP-2
      treatments.
AB  - Basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2)
      are actively pursued for stimulation of bone formation. To assess their promise
      for systemic therapy of osteoporosis, we ascertained the effects of bFGF and BMP
      2 on bone marrow cells in vitro. Bone marrow cells were obtained from young (8
      weeks) and adult (32 weeks) rats by femoral aspiration and were exposed to
      osteogenic medium (ie, basal medium with 10 mM beta-glycerolphosphate and 100 nM
      dexamethasone) containing the growth factors. The cell viability in osteogenic
      medium was reduced after 3 weeks but not if the concentration of beta
      glycerolphosphate/dexamethasone was reduced to 3 mM/30 nM. Unlike BMP-2, bFGF at
      2-50 ng/mL was capable of enhancing long-term cell viability. Continuous
      treatment of bone marrow cells for 3 weeks resulted in dose-dependent stimulation
      of mineralization by BMP-2, but not by bFGF, whose activity was optimal at 2-10
      ng/mL. To explore the effect of short-term exposure, bone marrow cells were
      treated with growth factors for 1 week and subsequent mineralization was
      investigated. BMP-2 exposure increased the extent of mineralization, but bFGF was
      not effective after the short exposure. We concluded bFGF was more potent (ie,
      required lower concentration) for stimulating osteogenic parameters, but BMP-2
      effects were lasting on the bone marrow cells.

PMID- 16462437
TI  - The Classic: Current concepts review: internal fixation of fractures of the
      thoracolumbar spine. 1984.

PMID- 16462438
TI  - Trends and variations in the use of spine surgery.
AB  - Examining trends and geographic variations in clinical care offers insights into
      changes in clinical decision making. We summarized data on spine surgical rates,
      trends, and variations in the United States to highlight areas of professional
      uncertainty and questions for future research. The United States has the highest
      rate of spine surgery in the world, but spine surgery shows wider geographic
      variations than most other procedures. For example, Medicare data for 2001 showed
      sixfold variations in spine surgery rates among United States cities, and 10-fold
      variations in spine fusion rates. United States spine surgery rates rose 55% in
      the 1980s. In the 1990s, studies of surgical rates became more difficult because
      20% of discectomies shifted to an out-patient setting. Extrapolations from states
      with ambulatory surgery data suggest overall lumbar surgery rates continued to
      rise throughout the 1990s. The most rapid increase was for spinal fusion, which
      tripled during the 1990s and accounted for an increasing proportion of all spine
      procedures. Some increases coincided with the introduction of new surgical
      implants. Despite new technologies, rates of repeat surgery after fusion were no
      lower than the rates after decompression alone. As new technology for spine
      surgery is introduced at an accelerating pace, we anticipate substantial changes
      in surgery patterns. Analysis of population-based data may be useful for
      surveillance of changes and their impacts.

PMID- 16462439
TI  - Triage for nonspecific lower-back pain.
AB  - Unremitting lower-back pain has long been a costly and personally devastating
      problem in society. Guidelines for the treatment of lower-back pain have provided
      evidence-based recommendations to help identify patients who will benefit from
      specific types of treatment in an effort to reduce costs and human suffering.
      However, there is little evidence that these guidelines are being applied in the
      daily practice of health care providers. Practical information is required to
      assist health care providers in triaging patients for specific treatments so that
      interventions can be targeted only to those who need them. In this way,
      iatrogenic complications and unnecessary costs can be contained. This chapter
      provides information on how to triage the patient with nonspecific lower-back
      pain for optimal care. The recommendations are supported by evidence-based
      guidelines, and when these are not available, best practice principles. Because
      appropriate treatment varies depending on the length of time a patient is
      suffering from lower-back pain, the chapter is divided into recommendations for
      acute, subacute, chronic and recurrent phases of lower-back pain. LEVEL OF
      EVIDENCE: Level V (expert opinion). See the Guidelines for Authors for a complete
      description of the levels of evidence.

PMID- 16462440
TI  - Nonspecific lower-back pain: surgical versus nonsurgical treatment.
AB  - We review evidence-based treatments for patients seeking care for lower-back pain
      and patients who have been diagnosed with nonspecific lower-back pain. The review
      is based on selected systematic reviews and national and international guidelines
      for the treatment of lower-back pain. Additional randomized controlled trials
      (ie, possibly those not previously included in the latest systematic reviews)
      were reviewed and added based on recommended procedures for the evaluation of
      methodological quality (ie, strong, moderate, and weak). In acute nonspecific
      lower-back pain (0-4 weeks duration of pain) there is moderate to strong evidence
      that self-care with over-the-counter medication and maintaining activity as
      tolerated or treatment with a limited number of sessions of manipulative therapy
      is effective for pain relief. In subacute nonspecific lower-back pain (4-12 weeks
      duration of pain) there is weak to moderate evidence that a graded activity
      program including exercises and cognitive behavioral treatment in combination is
      more efficient than usual care with regard to return to work. There is strong
      evidence that these programs reduce work absenteeism. In cases of chronic
      nonspecific lower-back pain (> 12 weeks duration of pain) a variety of treatments
      are available with limited and similar efficacy on pain and disability reduction.
      There is moderate evidence that surgery in chronic nonspecific lower-back pain is
      as effective as cognitive behavioral treatment with regard to pain, function,
      mood and return to work. Surgical indications for chronic nonspecific lower-back
      pain remain ill defined. LEVEL OF EVIDENCE: Level V (expert opinion). See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 16462441
TI  - Injection studies in spinal disorders.
AB  - Spinal injections have an important role in many centers in the diagnostic
      assessment and treatment of patient with various spinal disorders. In the
      literature, many studies describe the application, techniques, and potential
      benefit of spinal infections. It is well accepted morphologic alterations and
      pain correlate weakly because many imaging findings in patients with spinal
      symptoms can be found in asymptomatic individuals. Accordingly, one rationale for
      spinal injections is to provoke or eliminate pain presumably caused by the target
      spinal structure; this ostensibly allows a physician to make a better assessment
      of whether a particular morphologic alteration does or does not cause symptoms.
      Another rationale is to use spinal injections to support conservative treatment
      in patients who have from nerve root compromise, spinal stenosis, or facet joint
      osteoarthritis. Despite the widespread use of these spinal injections, their
      application is based widely on anecdotal experience and evidence that is not
      evidence based. We highlight the need for prospective randomized trials on the
      clinical efficiency of spinal injections and stress the importance for future
      considerations of cost effectiveness to justify their further application. LEVEL
      OF EVIDENCE: Level V (expert opinion). See the Guidelines for Authors for a
      complete description of the levels of evidence.

PMID- 16462442
TI  - Lumbar disc herniations: surgical versus nonsurgical treatment.
AB  - Lumbar disc herniation is among the most common causes of lower-back pain and
      sciatica. The cause(s) of lumbar disc herniation and the relation of lumbar disc
      herniation to back pain and sciatica have not been fully elucidated, but most
      likely comprise a complex combination of mechanical and biologic processes.
      Furthermore, the natural history of lumbar disc herniation seems generally to be
      favorable, leaving the optimum treatment for lumbar disc herniation a debate in
      the literature. Various nonoperative and operative treatment strategies have been
      tried with varying degrees of success. Treatment often involves patient
      education, physical therapy, alternative medicine options, and pharmaco-therapy.
      If these fail, surgical intervention is usually recommended. A literature search
      was conducted to evaluate the currently known effectiveness of traditional and
      novel non-operative and surgical techniques for the treatment lumbar disc
      herniation and to determine if there are substantive new advantages in these
      newer contemporary treatments or combinations thereof. A structured approach to
      treatment of a patient who may have a symptomatic lumbar disc herniation is
      presented, based on analysis of the current literature. No one method of
      nonoperative or operative treatment would seem definitively to be superior to
      another. Appropriate multidisciplinary treatment including behavioral analysis
      and support may offer the hope of improved outcomes for patients with lumbar disc
      herniation. LEVEL OF EVIDENCE: Level V (expert opinion). See the Guidelines for
      Authors for a complete description of the levels of evidence.

PMID- 16462443
TI  - Spinal stenosis: surgical versus nonsurgical treatment.
AB  - Lumbar spinal stenosis is being diagnosed increasingly in older people as
      advanced imaging studies become more widely available and clinicians become more
      familiar with the presentation of this common condition. For symptomatic
      patients, the goal of treatment is pain relief and improved function, but there
      is little empiric evidence to support many of the common interventions used. The
      relative risks and benefits of various surgical and nonsurgical treatments are
      poorly understood, and the result has been wide variations in the evaluation and
      treatment of spinal stenosis across geographic regions. Current practice
      recommendations are based on expert opinion that incorporates available evidence
      into existing clinical and biologic paradigms. For most individuals, initial
      treatment should focus on patient education, medications to control pain, and
      exercise and physical treatments to regain or maintain activities of daily
      living. Surgical treatment most commonly is considered in patients not improving
      with nonsurgical care. Decompressive laminectomy is the standard surgical
      procedure for patients with spinal stenosis. The addition of fusion with or
      without instrumentation is considered when spinal stenosis is accompanied by
      degenerative spondylolisthesis or related to concerns about instability. We
      review the available evidence for nonsurgical and surgical interventions, and
      highlight comparative results wherever applicable. LEVEL OF EVIDENCE: Level V
      (expert opinion). See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 16462444
TI  - Inflammatory arthritides of the spine: surgical versus nonsurgical treatment.
AB  - Ankylosing spondylitis and rheumatoid arthritis are disorders that cause marked
      alterations in the structure and function of the axial skeleton. Ankylosing
      spondylitis causes calcification of spinal structures causing limited motion.
      Rheumatoid arthritis causes synovial hypertrophy, joint destruction, and spinal
      instability. Surgical therapy for patients with ankylosing spondylitis corrects
      angular deformities with spinal osteotomies, and stabilization for spinal
      fractures. Spinal operative therapy for rheumatoid arthritis concentrates on
      correction of abnormal motion in the cervical spine. Advances in the medical
      therapy of spondyloarthritis have resulted in control of the inflammation of the
      axial skeleton halting the damage to spinal structures. The new biologic
      therapies for ankylosing spondylitis prevent progression of disease. Similarly,
      these same biologic therapies can also control the progression of rheumatoid
      arthritis including the cervical spine. The new medical therapies are very
      effective in preventing joint damage. The need for surgical intervention for
      patients with ankylosing spondylitis and rheumatoid arthritis will become a rare
      event in the setting of the new medical therapies for these inflammatory
      arthropathies.

PMID- 16462445
TI  - Treatment of instability and spondylolisthesis: surgical versus nonsurgical
      treatment.
AB  - Spondylolisthesis is a common cause of lower-back pain, radiculopathy, and
      neurogenic claudication among the adult population. Treatment should begin with
      nonoperative measures that may include physical therapy, aerobic exercise,
      epidural steroid injections, and homeopathic remedies. If these treatments fail,
      surgical intervention may provide the patient pain relief and improvement in
      neurologic symptoms. The use of instrumentation for posterolateral fusions as
      well as interbody fusion may improve clinical outcomes for those having surgical
      intervention. We discuss the current nonoperative modalities and surgical
      techniques treating degenerative spondylolisthesis. LEVEL OF EVIDENCE: Level V:
      Expert Opinion. See the Guidelines for Authors for a complete description of the
      levels of evidence.

PMID- 16462446
TI  - Failed back surgery syndrome: surgical and nonsurgical approaches.
AB  - Failed Back Surgery Syndrome is a common and challenging clinical problem. Often
      the anatomic pain source is unclear. Relevant outcome studies are rarely
      diagnosis specific, and high level research studies comparing surgical and
      nonsurgical approaches to Failed Back Surgery Syndrome studies have not been
      published to date. Surgical strategies focus on decompressing neural impingement
      or fusing unstable or putatively painful intervertebral discs. Nonsurgical
      interventions range from nerve root specific blocks for pain relief to
      multidisciplinary rehabilitation programs geared toward improving function. This
      paper reviews the most common interventions and concludes with recommendations
      for the care of the individual patient. LEVEL OF EVIDENCE: Level V (expert
      opinion). See the Guidelines for Authors for a complete description of the levels
      of evidence.

PMID- 16462447
TI  - Vertebral tumors: surgical versus nonsurgical treatment.
AB  - The treatment of spinal tumors represents a challenge to spine care
      professionals. Fortunately, the incidence of new cases of primary malignant bone
      tumors is lower compared with that of other tumors. In the United States
      approximately 2000 malignant bone tumors of 7000 new sarcomas are diagnosed each
      year. Of these, 4% to 20% (80-400 tumors) of bone tumors are spinal tumors.
      Metastatic tumors are the most frequent tumor of bone and the most frequent tumor
      of the spinal column regardless of the origin of the primary tumor. More than 90%
      of spinal tumors are metastatic. Thirty to seventy percent of patients who die
      from cancer have evidence of vertebral metastases visible on careful postmortem
      examination, with the potential that this number could reach 85% in patients with
      breast cancer. Less than 10% of patients with spinal tumors present with spinal
      instability requiring surgical treatment; this accounts for approximately 18,000
      new cases yearly. We will focus on the most recent advances in nonsurgical and
      surgical treatment of vertebral tumors. In surgical treatment, the evaluation and
      selection of patients, indications and surgical strategies, open and minimally
      invasive techniques, outcomes and complications will be discussed. LEVEL OF
      EVIDENCE: Level V (expert opinion). See the Guidelines for Authors for a complete
      description of the levels of evidence.

PMID- 16462448
TI  - Scoliosis: surgical versus nonsurgical treatment.
AB  - This article reviews the nonoperative and operative decision making process in
      idiopathic scoliosis in the adolescent and adult with additional comments about
      degenerative scoliosis. Because knowledge of the natural history of idiopathic
      scoliosis is essential for decision making, this will be covered first, as will
      the current knowledge concerning the long term outcomes of nonoperative and
      operative treatment. With the natural history as a background, I will discuss how
      the factors that are important in natural history effect decision making in the
      adolescent and adult. By using an evidence-based approach, hopefully a better
      decision-making process will result in improved outcomes. Additional treatment
      decisions regarding the choice of the specific nonoperative treatment methods as
      well as surgical decisions (fusion levels, approach, choice of implants) will not
      be covered. LEVEL OF EVIDENCE: Therapeutic study, level V (expert opinion). See
      the Guidelines for Authors for a complete description of the levels of evidence.

PMID- 16462449
TI  - Proximal migration can be measured accurately on standardized anteroposterior
      shoulder radiographs.
AB  - During the last decade, investigators of several studies have stressed the
      importance of early diagnosis and treatment of rotator cuff tears to improve
      outcome of surgical repair. Proximal migration of the humeral head is thought to
      be indicative for rotator cuff disorders. We wanted to assess the accuracy of
      proximal migration measurement on anteroposterior radiographs. Computed
      tomography scans and anteroposterior radiographs of 43 shoulders in 26 patients
      were taken using the same protocol. Proximal migration was measured as the
      acromiohumeral interval and the upward migration index. The mean absolute
      difference for the upward migration index was only 0.06 (standard deviation,
      0.07), this was less then 5% of the mean upward migration index measured on
      computed tomography reformations. The correlation coefficient and Bland-Altman
      plot showed a strong correlation between computed tomography and radiographic
      measurements, especially for the upward migration index (correlation coefficient,
      0.82). Our results indicate that measurement of subacromial space on
      anteroposterior radiographs, controlled for positioning, scaling, and individual
      differences by using the upward migration index, presents an accurate measurement
      for proximal migration. LEVEL OF EVIDENCE: Diagnostic study, Level I (testing of
      previously developed diagnostic criteria on consecutive patients--with
      universally applied reference "gold" standard). See the Guidelines for Authors
      for a complete description of levels of evidence.

PMID- 16462450
TI  - Changing demographics of patients with total joint replacement.
AB  - There has been a substantial change in the population demographics of patients
      who potentially will require total joint replacements. We studied data regarding
      temporal trends in physical condition, life expectancy, education, and other
      population demographics of individuals most likely to receive total joint
      replacements. Changes in this population during the last several decades
      correlate with temporal changes in the prevalence of joint disease and the
      incidence of total hip and knee replacements. Compared with several decades ago,
      patients currently receiving total joint replacements are almost 20% heavier,
      more physically active, three times more likely to have a high school or college
      education, and live more than 25% longer. Patients needing total joint
      replacements are more likely to be female, and twice as likely to receive a total
      knee replacement than a total hip replacement. Treatment choices and outcome
      expectations are best determined with accurate knowledge of current surgical
      science and current patient demographics. Therefore, it is important to realize
      that today's population most likely to receive total joint replacements is
      demographically different than in the past.

PMID- 16462452
TI  - Surgery for hallux valgus with proximal crescentic osteotomy causes variable
      postoperative pressure patterns.
AB  - We prospectively evaluated the results of plantar pressure measurement in 32
      patients (43 feet) who had a proximal crescentic osteotomy of the first
      metatarsal with a modified McBride procedure. The procedure's effectiveness in
      increasing weightbearing under the first ray, decreasing pressure under the
      second metatarsal head, and the relationship of radiographic measurements of
      first metatarsal length and position to postoperative pressure measurements were
      evaluated. Mean followup was 29 months. Average peak pressure increased
      postoperatively under the second metatarsal head. Almost identical numbers of
      feet had first metatarsal elevation (12) or depression (11) greater than 2 mm.
      Radiographic evidence of first metatarsal elevation, but not shortening, was
      associated with diminishing peak pressure and pressure-time integral under the
      first metatarsal head and hallux. Five feet that had first metatarsal elevation
      greater than 2 mm had new second metatarsal transfer lesions develop. Eleven feet
      preoperatively and nine feet postoperatively had symptomatic second metatarsal
      pressure lesions. One lesion persisted, 10 resolved, and eight new lesions
      developed. Control of the crescentic osteotomy in the sagittal plane was
      unpredictable despite modification of the surgical technique to plantarly
      displace the distal segment of the first meta-tarsal. Although average second
      metatarsal pressure increased postoperatively, there was variability in the
      correlation of radiographic change and pedobarographic measurements.

PMID- 16462451
TI  - Does alendronate prevent collapse in osteonecrosis of the femoral head?
AB  - Progression of collapse in osteonecrosis of the femoral head is related to the
      repair response, especially bone resorption around the necrotic region. A
      preliminary clinical study was done to determine whether systemic alendronate
      would prevent collapse and lead to pain relief in patients with osteonecrosis of
      the femoral head. Fourteen patients (20 hips) with osteonecrosis of the femoral
      head received daily administration of 5 mg alendronate (alendronate group) for 1
      year. Eight patients (13 hips) with osteonecrosis of the femoral head did not
      receive alendronate (control group). All patients had measurements of biochemical
      markers of bone turnover at entry into the study, and the patients in the
      alendronate group repeated the measurements at 3 months, 6 months, and 12 months.
      All patients had clinical and plain radiographic examinations at entry into the
      study and at 3 months, 6 months, and 12 months. The alendronate group showed a
      greater decrease of biochemical marker of bone resorption than biochemical marker
      of bone formation. The alendronate group showed a lower frequency of collapse of
      the femoral head and reported less hip pain than the control group. Our results
      suggest alendronate has the potential to prevent collapse of the femoral head,
      even with extensive necrosis, presumably by inhibiting bone resorption in the
      necrotic region. LEVEL OF EVIDENCE: Therapeutic study, level II (prospective
      comparative study). See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 16462454
TI  - Salvage of failed massive allograft reconstruction with endoprosthesis.
AB  - A subset of osteoarticular allograft reconstructions after tumor resection
      ultimately will fail in patients achieving long-term survival. There are several
      alternative surgical approaches to revising these reconstructions. We
      retrospectively evaluated the outcome of 20 patients who had allograft
      reconstruction with a modular endoprosthesis. All patients had a failed massive
      allograft (average length, 15.7 cm) after tumor resection about the shoulder and
      knee. The reasons for original allograft failure were fracture (14 patients),
      infection (five patients), and both (one patient). Followup of the patients
      averaged 159.7 months (range, 63-293 months) after allograft reconstruction and
      77 months (range, 24-234 months) after endoprosthetic revision. The average
      number of operative procedures each patient had was 4.1 (range, 2-15 procedures).
      Two patients had amputations for resistant periprosthetic infections. A
      successful revision procedure was accomplished in 80% of the patients, and 90% of
      the patients retained functional limbs at recent followup. The predicted 5-, 10-,
      and 15-year survivals were 92%, 55% and 28% respectively. Musculoskeletal Tumor
      Society scores averaged 76% (range, 60-93.3%). When used to salvage massive
      allograft failure from infection and fractures, endoprosthetic revision preserves
      limb function with minimal complications. LEVEL OF EVIDENCE: Therapeutic study,
      Level IV (case series). See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 16462453
TI  - Complications of cemented long-stem hip arthroplasties in metastatic bone
      disease.
AB  - It is controversial whether a cemented long-stem femoral arthroplasty is a safe
      surgical option for patients with meta-static bone disease of the hip. Cemented
      long stems increase the risk of embolic cascades and may cause subsequent
      cardiopulmonary complications, particularly in patients with metastatic disease.
      We retrospectively reviewed results of 29 long-stem cemented femoral
      arthroplasties in 27 patients in which surgical techniques that minimized
      intramedullary debris and canal pressurization were used. The surgical techniques
      minimized intraoperative cement-related emboli with aggressive medullary lavage,
      intraoperative canal suctioning during cementation, use of early low-viscosity
      polymethylmethacrylate, and slow, controlled insertion of the long-stem
      prosthesis. Cement-associated hypotension occurred in four (14%) patients,
      sympathomimetics were administered in nine (31%) patients, and a worsening mental
      status occurred postoperatively in one (3%) patient. There were no cement
      associated desaturation events, cardiac arrests, or intraoperative deaths. No
      patients required prolonged intubation, and there were no postoperative
      cardiopulmonary events. Cemented long-stem femoral arthroplasty is a safe
      procedure for patients with high-risk metastatic disease. Increased awareness of
      cement-related cardiopulmonary pathophysiology, and modifying conventional
      surgical techniques can minimize cement-associated complications. LEVEL OF
      EVIDENCE: Therapeutic study, Level IV (case series). See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 16462455
TI  - Does screw configuration affect subtrochanteric fracture after femoral neck
      fixation?
AB  - A subtrochanteric femur fracture after cannulated screw fixation of a femoral
      neck fracture is a devastating complication. We hypothesized that an apex-distal
      screw orientation would tolerate higher loads to subtrochanteric fracture. Human
      cadaveric femora were instrumented with three cannulated screws in either an apex
      distal or an apex-proximal configuration. Specimens were loaded along the
      mechanical axis to failure creating a subtrochanteric femur fracture. Ultimate
      load to failure and the effect of bone density on load to failure were compared
      between groups. There was a greater load to failure in the apex-distal group
      compared with the apex-proximal group. The mean force to fracture in the apex
      distal group (11,330 N; standard deviation = 3151 N) was greater than the mean
      force to fracture in the apex-proximal group (7795 N; standard deviation = 3194
      N). Previous investigations have shown improved femoral neck fixation with an
      apex-distal configuration, but none has examined the relationship between screw
      orientation and subtrochanteric fractures. Our observations support the use of an
      apex-distal configuration for cannulated screw fixation of femoral neck
      fractures.

PMID- 16462456
TI  - Shear does not necessarily inhibit bone healing.
AB  - Interfragmentary shear has been perceived as inhibitory to bone healing. We think
      this is because of inadequate balance between stimulatory and disruptive
      interfragmentary displacement magnitudes in the shear direction. We hypothesized
      that pure shear is not necessarily detrimental to bone healing. This was
      investigated by comparing bone healing under interfragmentary torsional shear,
      axial compression, and no applied motion. Applied motion was controlled carefully
      with similar interfragmentary principal strain magnitudes found to stimulate
      healing under axial compression. The observation period was 8 weeks. Torsional
      rotation stimulated intercortical mineralized callus formation with greater area
      than the group without applied motion, and led to a stiffness and rate of bony
      bridging similar to that of the no motion group. Axial compression stimulated
      less intercortical mineralized callus of a lower density than the no motion
      group, and there also was little bridging. These results support the hypothesis
      that interfragmentary shear does not necessarily inhibit bone healing.

PMID- 16462457
TI  - Second application of low-energy shock waves has a cumulative effect on free
      nerve endings.
AB  - Some physicians recommend treating tendinopathies with multiple sessions of shock
      waves. Some evidence, however, suggests shock wave application can induce nerve
      fiber degeneration. We questioned whether repeated shock wave application
      provides a cumulative effect on nerve fibers compared with the effect of one
      application. One thousand shock wave impulses of an energy flux density of 0.08
      mJ/mm were applied to the foot pad of 32 rats. After 14 days, 16 rats received a
      second application. The foot pads were resected on Days 7, 14, 28, and 42.
      Sections were processed immunohistochemically using antibodies for sensory nerve.
      We compared the number of epidermal nerve fibers in rats that received one
      application of shock waves with the fibers in rats that received two
      applications. During the first 4 weeks, there was nearly complete degeneration of
      epidermal nerve fibers in both groups. By the end of 6 weeks, reinnervation of
      the epidermis began in the single-treatment group. Reinnervation occurred slower
      in the repeated-treatment group. These data show that a second application has a
      cumulative effect on nerve fibers. Our data suggest multiple applications of low
      energy shock waves might a provide longer-lasting antinociceptive effect.

PMID- 16462458
TI  - Biomechanical basis for tendinopathy.
AB  - Tendinopathy affects millions of people in athletic and occupational settings and
      is a nemesis for patients and physicians. Mechanical loading is a major causative
      factor for tendinopathy; however, the exact mechanical loading conditions
      (magnitude, frequency, duration, loading history, or some combinations) that
      cause tendinopathy are poorly defined. Exercise animal model studies indicate
      that repetitive mechanical loading induces inflammatory and degenerative changes
      in tendons, but the cellular and molecular mechanisms responsible for such
      changes are not known. Injection animal model studies show that collagenase and
      inflammatory agents (inflammatory cytokines and prostaglandin E1 and E2) may be
      involved in tendon inflammation and degeneration; however, whether these
      molecules are involved in the development of tendinopathy because of mechanical
      loading remains to be verified. Finally, despite improved treatment modalities,
      the clinical outcome of treatment of tendinopathy is unpredictable, as it is not
      clear whether a specific modality treats the symptoms or the causes. Research is
      required to better understand the mechanisms of tendinopathy at the tissue,
      cellular, and molecular levels and to develop new scientifically based modalities
      to treat tendinopathy more effectively.

PMID- 16462459
TI  - Osteolysis caused by tibial component debonding in total knee arthroplasty.
AB  - Late failure of total knee arthroplasties usually results from ultrahigh
      molecular weight polyethylene wear or implant loosening. Early failure from
      osteolysis is uncommon. However, we treated a patient with a failed total knee
      arthroplasty from osteolysis that developed 2 years postoperatively. The failure
      was associated with tibial component debonding from the cement mantle with
      abundant cement and metal debris. Although there was some third-body debris in
      the ultrahigh molecular weight polyethylene insert surface, the insert wear was
      not extensive. Although abundant cement and metal debris were found in the
      periarticular soft tissues, no ultrahigh molecular weight polyethylene was seen
      in histologic specimens under polarized light. The osteolysis seems to have been
      caused primarily by debris generated from debonding and torsional motion at the
      tibial baseplate-cement interface rather than the bearing surface. Although this
      failure mechanism has been well recognized in cemented total hip arthroplasties,
      it has not been reported to be a substantial cause of failure in total knee
      arthroplasties.

PMID- 16462460
TI  - Case reports: a rare cause of radicular complaints: ligamentum flavum hematoma.
AB  - Hematomas in the lumbar ligamentum flavum are rare and may generate signs and
      symptoms of lumbar nerve root compression or neurogenic claudication similar to
      the far more common degenerative diseases. The pathogenesis of these hematomas is
      unclear. Ruptured irregular vessels of the degenerated and hypertrophic
      ligamentum flavum were assumed. We diagnosed three patients with a flavum
      hematoma intraoperatively leading to radicular complaints and spinal
      claudication. One occurred as a complication of local infiltration therapy, and
      the other two patients reported minor trauma as the releasing factor. Using
      spinal magnetic resonance imaging, a preoperative diagnosis is possible but the
      differentiation to synovial cysts is difficult. Surgical resection of the
      ligamentum flavum, including the hematoma, provided adequate treatment in these
      patients.

PMID- 16462461
TI  - A 60-year-old man with right hip pain.

PMID- 16462462
TI  - Radial overgrowth and deformity after metaphyseal fracture fixation in a child.

PMID- 16462464
TI  - Cerebral mycotic aneurysms treated with a neuroform stent: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe the first documented endovascular treatment
      of proximal intracranial mycotic aneurysms by a self-expanding, flexible,
      dedicated, intracranial Neuroform stent. Treatment with this stent rapidly
      obliterated the aneurysms, eliminated the need for additional coiling, and
      maintained the patency of the parent arteries. CLINICAL PRESENTATION: A 47-year
      old male patient with infective endocarditis presented with ischemic stroke and
      minimal subarachnoid hemorrhage. Cerebral angiography demonstrated a fusiform
      aneurysm of the supraclinoid segment of the left internal carotid artery and
      horizontal segment of the left middle cerebral artery, with superimposing side
      wall focal aneurysms. Despite antibiotic therapy, the focal aneurysms
      progressively enlarged, as demonstrated on a subsequent cerebral angiogram at Day
      11. INTERVENTION: A 4-mm x 2-cm Neuroform stent was deployed along the fusiform
      aneurysm of the left supraclinoid internal carotid artery and the horizontal
      middle cerebral artery M-1 segment encompassing the focal side-wall aneurysms
      with preserved patency of the parent arterial segments. CONCLUSION: Endovascular
      stent placement can be an effective treatment for proximal intracranial mycotic
      aneurysms that fail to respond to medical therapy.

PMID- 16462465
TI  - Obliteration of carotid-cavernous fistulas using direct surgical and coil
      assisted embolization: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Carotid cavernous fistulas (CCF) type-D are often
      refractory to endovascular treatment. Surgery for these lesions is a well
      described alternative option. A case of combined pretemporal approach to the
      cavernous sinus and direct coiling of CCF is presented as well as treatment
      options in cases of recurrent and intractable fistulas. CLINICAL PRESENTATION: A
      58-year-old woman with three years' history of double vision, headache, and
      numbness of the right upper extremity. On clinical examination she was noted to
      have congestion in the left eye with neurological examination without any
      deficits. Angiography revealed a type-D fistula.. INTERVENTION: Patient underwent
      craniozygomatic pretemporal approach and direct coiling of the fistula.
      Intraoperative angiogram was done to confirm adequate obliteration of the fistula
      and preservation of flow in the parent artery.. CONCLUSION: Although the first
      line treatment option for symptomatic cavernous sinus fistulas is endovascular
      embolization, surgery is indicated in cases where it fails to achieve
      satisfactory results. This is especially important when the patient has
      progressive neurological deficit, and in cases of compromised venous drainage.
      Direct coil-assisted obliteration of the fistula is a successful treatment option
      for these lesions..

PMID- 16462466
TI  - Bilateral stimulation of the globus pallidus internus to treat choreathetosis in
      Huntington's disease: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Huntington's disease (HD) produces debilitating motor
      abnormalities that are poorly responsive to medical therapy. Deep brain
      stimulation (DBS) may offer a treatment option for afflicted patients, but its
      role in the management of HD remains unclear. In the present case, DBS leads were
      implanted bilaterally into the posteroventral globus pallidus internus (GPi) to
      control disabling and medically intractable choreathetosis in a severely affected
      HD patient. The surgical procedure, intraoperative electrophysiological findings,
      and 12-month postoperative course, with patient video, are presented. CLINICAL
      PRESENTATION: This 41-year-old man with genetically confirmed HD developed motor
      symptoms at age 28. He had completed multiple medical trials without alleviation
      of his progressive and debilitating choreathetosis. Extensive clinical
      assessment, including neuropsychological testing, was performed to determine
      surgical candidacy. INTERVENTION: DBS leads were bilaterally implanted, under
      stereotactic guidance, into the posteroventral GPi. Disease progression and
      symptom control were assessed at regular postoperative intervals. Bilateral
      pallidal stimulation produced a dramatic reduction in choreathetoid movements and
      improvement in overall motor functioning. The patient also exhibited
      normalization of body weight, mood, and energy level, as well as improved
      performance of activities of daily living. These effects were sustained at 1 year
      after surgery. CONCLUSION: The clinical benefits of DBS observed in this HD
      patient were comparable to those reported in other hyperkinetic disorders and
      demonstrate that pallidal stimulation can provide long-term alleviation of HD
      associated choreathetosis.

PMID- 16462467
TI  - Chronic cortical stimulation for amyotropic lateral sclerosis: a report of four
      consecutive operated cases after a 2-year follow-up: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: From April to July 2002, four consecutive patients
      affected by amyotrophic lateral sclerosis (ALS) were surgically treated with
      bilateral chronic cortical stimulation.. CLINICAL PRESENTATION: The preoperative
      diagnostic assessment was based on the results of a neurological examination,
      integrated by the ALS functional rating scale, electromyography, magnetic
      resonance imaging, and single-photon emission computed tomography (SPECT). In
      particular, SPECT provided a remarkable contribution in terms of its ability to
      demonstrate specific morphological and metabolic ALS lesions of the brain.
      INTERVENTION: The postoperative neurological follow-up was based mainly on the
      assessment of neurological status and the ALS functional rating scale, together
      with SPECT. Two years after surgery, at clinical examination, two patients
      demonstrated mild progression of their illness, and SPECT findings disclosed
      complete disappearance of ALS cerebral lesions, with apparent recovery of brain
      anatomic integrity. The third patient committed suicide. In the fourth patient,
      the disease seemed to have progressed inexorably at the time of clinical and
      SPECT monitoring, after transient improvement during the first 3 months after
      surgery.. CONCLUSION: These preliminary results are surprising, because they
      suggest that chronic cortical stimulation can play a role against ALS and deserve
      confirmation in larger numbers of patients and for a longer follow-up. We present
      the theoretical grounds for these findings, as well as the diagnostic and
      surgical procedures and results..

PMID- 16462468
TI  - Resolution of an infectious pseudoaneurysm in a cervical petrous carotid vein
      bypass graft after covered stent placement: case report.
AB  - OBJECTIVE AND IMPORTANCE: Covered stenting of the carotid artery has been used to
      treat aneurysms and dissections. We describe a unique case of covered stenting in
      the setting of an infected psuedoaneurysm in a previously placed cervical-to
      petrous vein bypass graft. Operating in an infected field and reopening a
      surgical wound at the craniocervical junction that had previously been exposed to
      penetrating trauma created substantial risks to open surgical repair. We
      therefore chose an endovascular strategy to repair this lesion. CLINICAL
      PRESENTATION: A 57-year-old diabetic man with a previously placed cervical-to
      petrous vein bypass graft presented with chronic otitis media and acute
      hemorrhage from his right external auditory meatus. Evaluation revealed an
      infectious pseudoaneurysm of the vein graft at the skull base. TECHNIQUE: The
      patient was treated with intravenous antibiotics and endovascular placement of an
      8-mm x 25-mm polytetrafluoroethylene-covered stent across the pseudoaneurysm.
      Angiography obtained 8 months later confirmed successful obliteration of the
      lesion. CONCLUSION: The patient's clinical outcome was excellent. Despite the
      active infection, covered stenting of the pseudoaneurysm was an effective
      treatment strategy, obviating the need for open debridement and graft revision.

PMID- 16462469
TI  - Spinal cord compression in a patient with a pain pump for failed back syndrome: a
      chalk-like precipitate mimicking a spinal cord neoplasm: case report.
AB  - OBJECTIVE AND IMPORTANCE: The use of intrathecal morphine has been effective with
      few complications for chronic intractable pain of both benign and malignant
      origins. A rare but serious problem that exists is the formation of an
      inflammatory mass at the catheter tip of the pain pump. CLINICAL PRESENTATION: We
      report the case of a 67-year-old female patient with failed back syndrome who
      presented with sensory complaints and back pain. INTERVENTION: Magnetic resonance
      imaging revealed impingement on the thoracic cord by a mass. The mass was
      originally thought to be a spinal cord tumor; however, operation and chemical
      analysis of the mass showed that it was a bupivacaine precipitate at the tip of
      the catheter of the pain pump. CONCLUSION: This is the first such case, to our
      knowledge, of a bupivacaine precipitate mimicking a spinal cord tumor.

PMID- 16462470
TI  - Aneurysm of the anterior inferior cerebellar artery-posterior inferior cerebellar
      artery variant: case report with anatomical description in the cadaver.
AB  - OBJECTIVE AND IMPORTANCE: The authors report a very rare case of an aneurysm at
      the distal segment of the anterior inferior cerebellar artery-posterior inferior
      cerebellar artery (AICA-PICA) variant along with a description of the surgical
      anatomy of this variation in a cadaveric specimen. CLINICAL PRESENTATION: A 44
      year-old woman experienced the sudden onset of severe headache and vomiting.
      Computed tomographic scanning revealed subarachnoid and intraventricular
      hemorrhage. Cerebral angiography demonstrated a saccular aneurysm arising from
      the tonsillomedullary segment of the right PICA and a second aneurysm arising
      from the cortical segment of the common trunk of an AICA-PICA variation.
      INTERVENTION: Via bilateral suboccipital craniotomy, both aneurysms were clipped.
      CONCLUSION: Only two cases of aneurysms arising from an AICA-PICA variation have
      been reported in the literature and no detailed description of the surgical
      anatomy of this variation has been carried out in previous publications. To our
      knowledge, the present report is the first description of a clinical case along
      with a detailed surgical anatomic study in a cadaver.

PMID- 16462473
TI  - Outcome of surgical clipping of unruptured aneurysms as it compares with a 10
      year nonclipping survival period.
AB  - OBJECTIVE: Recent studies on the natural history of unruptured intracranial
      aneurysms dictate that we reevaluate the risks and benefits of surgical
      intervention as it compares with the natural course. We analyzed the outcome of
      surgical clipping of a patient cohort with unruptured aneurysms as it compares
      with a 10 year nonclipping survival period on the basis of two previously
      published studies (International Study on Unruptured Intracranial Aneurysms and a
      study by Juvela et al. [36] from Helsinki). METHODS: Data on 148 unruptured
      aneurysms in 116 consecutive surgically treated patients were prospectively
      recorded and retrospectively analyzed. The overall majority were diagnosed with
      cerebral angiography. Data analyzed included aneurysmal properties and clinical
      outcomes including surgical related mortalities and morbidities. The observed
      outcomes were compared with the expected outcome of a 10 year nonclipping
      survival period if the patient cohort was included in recently reported studies
      on unruptured aneurysms. More than 1 year follow-up was available in 93.1% (108)
      of patients and follow-up cerebral angiography was performed in 80% (93) of
      patients. RESULTS: Mean age was 53.57 years. There were 25 (16.8%) small
      aneurysms (less than 7 mm), 70 (47.2%) aneurysms 7 to 12 mm in size, 41 (27.70%)
      large (13-24 mm), and 12 (8.10%) giant (>25 mm) aneurysms. Posterior circulation
      aneurysm comprised 13.51%. One hundred forty-three (96.62%) aneurysms were
      successfully clipped, and 3.37% were either wrapped or later coiled. Surgical
      related mortality was 0.82% (1 patient because of air embolism). Surgical related
      permanent morbidity was 3.44% (4 patients) and transient surgical-related mild
      morbidities was 7.7% (9 patients). Immediate postsurgical good outcome (Glasgow
      Outcome Score = 4-5) was 87.93% (102 patients) and 95.68% in 3 months (111
      patients). At 1 year, the modified Rankin scale scores were 0 to I = 102, II = 3,
      III = 2, IV = 1, and V = 0. Residual aneurysms were seen in none of the
      postoperative angiograms (93 patients). Using the chi method, the comparison of
      the expected to the observed mortality and morbidity revealed a statistically
      significant difference in the mortality in favor of surgical clipping (P = 0.034
      when compared with the International Study on Unruptured Intracranial Aneurysms
      and P = 0.05 when compared with the Juvela et al. [36] study). There was no
      statistically significant difference in the permanent morbidity. CONCLUSION:
      Studies on natural history of unruptured intracranial aneurysms suggest 10 year
      cumulative bleeding-related mortality and severe morbidity of no less than 7.5%.
      In our study, surgical clipping resulted in an 0.8% rate of mortality and 3.4%
      permanent morbidity. This suggests that surgical clipping has the potential of a
      superior outcome to the natural history of patients who have an estimated life
      expectancy of no less than 10 years.

PMID- 16462474
TI  - Epidemiology of the size distribution of intracranial bifurcation aneurysms:
      smaller size of distal aneurysms and increasing size of unruptured aneurysms with
      age.
AB  - OBJECTIVE: To explore the epidemiology of the size distribution of intracranial
      bifurcation aneurysms at different locations and to specifically test the
      hypothesis that distal vessels develop, on average, smaller aneurysms. METHODS: A
      database detailing all aneurysm cases admitted to Massachusetts General Hospital
      from 1991 to 2003 was reviewed. Aneurysms were classified by location and size.
      The distribution of aneurysms by sizes at differing origin sites was then
      compared. RESULTS: We identified 1673 aneurysms for study; 854 were ruptured and
      819 were unruptured; 58 lesions were classified as distal middle cerebral artery
      and anterior cerebral artery, of which 26 were unruptured and 32 were ruptured.
      Analysis of the kernel density estimates for the distribution of aneurysm sizes
      revealed that aneurysms at distal locations and the posterior-inferior cerebellar
      artery location were smaller than those at other locations in the circle of
      Willis. The mean size of ruptured distal aneurysms at 5.7 mm (95% confidence
      interval 4.8-6.5), or ruptured posterior-inferior cerebellar artery aneurysms at
      7.1 mm (95% confidence interval 6.3-7.8) was smaller than the average size for
      basilar, middle cerebral artery, or ICA aneurysms occurring proximally in the
      Circle of Willis. The decrease in the mean size of the distal lesions is caused
      by a relative paucity of aneurysms above 10 mm in size. Although ruptured
      aneurysms showed no change in size with age, unruptured lesions at most
      intracranial locations increased in size with age. CONCLUSION: The distribution
      of aneurysm sizes differs according to location in the intracranial vasculature
      in this single institution series. Smaller aneurysm sizes are observed for
      "distal" aneurysms than at other locations in the Circle of Willis. We
      hypothesize that this may be related to Laplace's Law, which states that the
      "critical" size for aneurysm rupture is related to the parent artery wall
      thickness. The larger size of unruptured aneurysms in older patients in this
      study may reflect referral bias or a biological model in which a subset of
      smaller "unstable" aneurysms are prone to rupture. Because distal aneurysms
      present at smaller sizes compared with aneurysms originating proximally on the
      Circle of Willis, prospective studies that focus on the rupture risk of this
      subset of intracranial aneurysms are appropriate for future investigation.

PMID- 16462475
TI  - Repeated endovascular coil occlusion in 350 of 2759 intracranial aneurysms:
      safety and effectiveness aspects.
AB  - OBJECTIVE: Evaluation of the safety and effectiveness of endovascular retreatment
      of intracranial aneurysms with detachable coils. METHODS: Retrospective analysis
      of clinical outcome as well as angiographic studies both before and after coil
      retreatment. The indication for retreatment was based on either inadequate
      occlusion after previous treatment or recurrent perfusion of the aneurysm.
      RESULTS: A total of 2759 intracranial aneurysms in 2360 patients were treated by
      endovascular coil occlusion. Of those, 350 (12.3%) aneurysms underwent a second
      treatment, and 94 (3.4%) aneurysms underwent three or more treatment sessions.
      The second treatment sessions were performed an average of 27.2 months after the
      previous procedure. The third and following treatment sessions were conducted an
      average of 25.3 months after the previous procedure. Initial treatment resulted
      in 100% occlusion in 63.7% of aneurysms. One hundred percent occlusion was
      achieved in only 46.9% of the second and 35.2% of the third and following
      sessions. Stent-assisted coil treatment was used in 5.6% of initial, 28.0% of
      second, and 20.7% of third and following sessions. Initial treatment sessions
      were uneventful in 83.2% of cases, second sessions in 86.9% of cases, and third
      and following sessions in 87.6% of cases. The morbidity-mortality rate for 495
      retreatment sessions was 2.2% (n = 11). CONCLUSION: The natural course of
      aneurysm remnants or recurrent aneurysm perfusion after coil treatment is not
      completely understood. The low risk of bleeding from partially filled aneurysms
      must be balanced against the procedure-related risks of retreatment. Great
      caution is recommended for the treatment of asymptomatic recurrent aneurysms.

PMID- 16462476
TI  - Advancements in carotid stenting leading to reductions in perioperative morbidity
      among patients 80 years and older.
AB  - OBJECTIVE: Patients 80 years and older are generally considered to be at an
      increased risk for stroke and death from carotid endarterectomy. High-risk status
      often qualifies them for entry into a carotid angioplasty and stenting (CAS)
      trial. The aim of this study is to report periprocedure (0-30 d) morbidity and
      mortality among elderly patients undergoing CAS with and without distal embolic
      protection in an intention-to-treat analysis. METHODS: A retrospective review was
      performed to evaluate the medical records and imaging studies of patients 80
      years or older who underwent attempted CAS procedures with and without distal
      embolic protection between June 1996 and February 2004. RESULTS: Ages of the 75
      patients identified in our review ranged from 80 to 91 years (average 83.1 yr);
      41 were men. Internal carotid artery stenosis ranged from 60 to 95% (mean 78.3%).
      Forty-two patients had symptoms (transient ischemic attack, 29; stroke, 13), and
      33 patients were asymptomatic. Total event rates were major stroke, 4% (3
      patients); minor stroke, 6.7% (5 patients); death, 4% (3 patients). Rates in the
      unprotected group (35 patients) were major stroke, 8.6% (3 patients); minor
      stroke, 5.7% (2 patients); major stroke/death, 14.3% (5 patients). Rates in the
      protected group (40 patients) were major stroke, 0; minor stroke, 7.5% (3
      patients); major stroke/death, 0; (P < 0.05). CONCLUSION: These results suggest
      that elderly patients undergoing CAS with adjunctive distal embolic protection
      are at a lower risk of periprocedure adverse events. Routine clopidogrel use,
      smaller hardware profile, patient selection, and increased experience likely
      contributed to these results.

PMID- 16462477
TI  - Management of vestibular schwannomas that enlarge after stereotactic
      radiosurgery: treatment recommendations based on a 15 year experience.
AB  - OBJECTIVE: Stereotactic radiosurgery is an effective alternative to surgical
      resection for the majority of patients with vestibular schwannomas (VS). However,
      after radiosurgery, the imaging characteristics of VSs are variable, and correct
      interpretation is critical to prevent unnecessary surgery for these patients.
      METHODS: A retrospective study of 208 consecutive patients with unilateral VS
      having radiosurgery between March 1990 and December 2001. Thirty (14%) patients
      had tumors that enlarged at least 2 mm after radiosurgery. The median follow-up
      after radiosurgery was 56 months (range 24-132 mo). RESULTS: The median time to
      tumor enlargement was 9 months (5-60 mo). The median volume increase was 75%. A
      loss of central enhancement was noted in 28 (93%) patients. Six (20%) patients
      had new symptoms noted at the time of tumor enlargement including hemifacial
      spasm (n = 2), ataxia (n = 2), trigeminal neuralgia (n = 1), and facial numbness
      (n = 1). Additional treatment was performed at the time of initial enlargement in
      3 patients (resection, n = 2; ventriculoperitoneal shunt, n = 1). In the 28
      patients who did not undergo resection at the time of initial enlargement, three
      patterns were identified on later imaging. Sixteen (57%) patients showed eventual
      tumor regression (type 1), and eight (29%) patients had tumors that increased and
      remained larger but did not show progressive enlargement (type 2). Four (14%)
      patients showed progressive enlargement on serial imaging (type 3) and underwent
      additional treatment (resection, n = 3; stereotactic radiation therapy, n = 1).
      CONCLUSION: Tumor expansion after VS radiosurgery rarely denotes a failed
      procedure, and the majority of patients only require further imaging.
      Approximately one third of tumors that enlarge will remain increased in size
      compared with the time of radiosurgery but will not show sequential growth.
      Additional tumor treatment should be reserved only for patients who demonstrate
      progressive tumor enlargement on serial imaging (2% in this series).

PMID- 16462478
TI  - Management of cranial base chondrosarcomas.
AB  - OBJECTIVE: Chondrosarcomas are rare, infiltrative, progressive lesions that occur
      at the cranial base. Their intimate association with cranial nerves and major
      vessels of the head and neck often precludes complete surgical resection.
      METHODS: Between 1983 and 2003, 23 patients (14 females, 9 males) were treated at
      our institution with the diagnosis of chondrosarcoma of the cranial base (mean
      age at presentation, 43 yr). A retrospective chart review was performed to
      evaluate presentation, management, and adjunctive treatment. All living patients
      were contacted for a current examination and disease status. RESULTS: The 23
      patients underwent 43 surgical resections. Follow-up ranged from 8 months to 25
      years (mean, 97 mo). Ten patients underwent various adjuvant radiation therapies.
      Five patients have died. Four patients have no evidence of disease, and 13 have
      residual tumor. One was lost to follow-up. Of 14 patients with 5 years of follow
      up, 13 are living. Therefore, the absolute 5 year survival rate is 93%. The 10
      year survival rate is 71%. CONCLUSION: Because of the intricate nature of the
      cranial base, a team approach is preferable for managing these challenging
      lesions. Maximum cytoreductive surgery should be pursued as an initial strategy
      to minimize neurological injury. Adjuvant stereotactic radiosurgery can be used
      to treat residual disease or small recurrences. This cohort also illustrates that
      patients with chondrosarcomas have better long-term survival rates than patients
      with chordomas of the cranial base.

PMID- 16462479
TI  - Magnetic resonance imaging-based volumetric analysis of basal ganglia nuclei and
      substantia nigra in patients with Parkinson's disease.
AB  - OBJECTIVE: Parkinson's disease (PD) is associated with well-documented
      morphological changes in substantia nigra and basal ganglia nuclei. This study
      evaluates the ability of magnetic resonance imaging to detect these changes and
      investigates the relationship between severity of clinical findings and degree of
      morphological change. This correlation may provide valuable information in early
      diagnosis of PD. METHODS: Sixteen patients with early stage PD, eight patients
      with advanced PD, and eight normal controls were studied by 3T magnetic resonance
      imaging. The whole brain volume and the volumes of the caudate, putamen, globus
      pallidus, and substantia nigra were calculated on three-dimensional reconstructed
      images. RESULTS: Putamen volume was significantly diminished in patients with
      early PD and advanced PD compared with that in controls (P < 0.05), and the
      percentage of atrophy was 12.5 and 26.5%, respectively. The putamen volume was
      negatively correlated with Hoehn and Yahr staging (r = -0.720, P < 0.001).
      Pallidal volume was reduced only in advanced PD (P = 0.023). There were no
      significant differences in total brain, caudate, or substantia nigra among these
      three groups CONCLUSION: Magnetic resonance imaging-based volumetric measurement
      is a sensitive method in the assessment of morphological changes of PD in vivo.
      The putamen atrophy was correlated with the severity of clinical findings. The
      volumetric measurement of putamen could potentially be a useful indicator of PD
      in the early stage.

PMID- 16462480
TI  - Concussion in professional football: recovery of NFL and high school athletes
      assessed by computerized neuropsychological testing--Part 12.
AB  - OBJECTIVE: Acute recovery from concussion (mild traumatic brain injury) is
      assessed in samples of NFL and high school athletes evaluated within days of
      injury. METHODS: All athletes were evaluated within days of injury using a
      computer-based neuropsychological test and symptom inventory protocol. Test
      performance was compared to preinjury baseline levels of a similar but not
      identical group of athletes who had undergone preseason testing. Statistical
      analyses were completed using Multivariate Analysis of Variance (MANOVA).
      RESULTS: NFL athletes demonstrated a rapid neuropsychological recovery. As a
      group, NFL athletes returned to baseline performance in a week with the majority
      of athletes having normal performance two days after injury. High school athletes
      demonstrated a slower recovery than NFL athletes. CONCLUSION: Computer-based
      neuropsychological testing was used within the overall medical evaluation and
      care of NFL athletes. As found in a prior study using more traditional
      neuropsychological testing, NFL players did not demonstrate decrements in
      neuropsychological performance beyond one week of injury. High school players
      demonstrated more prolonged neuropsychological effects of concussion.

PMID- 16462481
TI  - Examining concussion rates and return to play in high school football players
      wearing newer helmet technology: a three-year prospective cohort study.
AB  - OBJECTIVE: The purpose of this study was to compare concussion rates and recovery
      times for athletes wearing newer helmet technology compared to traditional helmet
      design. METHODS: This was a three-year, prospective, naturalistic, cohort study.
      Participants were 2,141 high school athletes from Western Pennsylvania.
      Approximately half of the sample wore the Revolution helmet manufactured by
      Riddell, Inc. (n = 1,173) and the remainder of the sample used standard helmets
      (n = 968). Athletes underwent computerized neurocognitive testing through the use
      of ImPACT at the beginning of the study. Following a concussion, players were
      reevaluated at various time intervals until recovery was complete. RESULTS: In
      the total sample, the concussion rate in athletes wearing the Revolution was 5.3%
      and in athletes wearing standard helmets was 7.6% [chi (1, 2, 141) = 4.96, P <
      0.027]. The relative risk estimate was 0.69 (95% confidence interval = 0.499-
      0.958). Wearing the Revolution helmet was associated with approximately a 31%
      decreased relative risk and 2.3% decreased absolute risk for sustaining a
      concussion in this cohort study. The athletes wearing the Revolution did not
      differ from athletes wearing standard helmets on the mechanism of injury (e.g.,
      head-to-head strike), on-field concussion markers (e.g., amnesia or loss of
      consciousness), or on-field presentation of symptoms (e.g., headaches, dizziness,
      or balance problems). CONCLUSION: Recent sophisticated laboratory research has
      better elucidated injury biomechanics associated with concussion in professional
      football players. This data has led to changes in helmet design and new helmet
      technology, which appears to have beneficial effects in reducing the incidence of
      cerebral concussion in high school football players.

PMID- 16462482
TI  - Current treatment strategies and outcomes in the management of symptomatic
      vertebral hemangiomas.
AB  - OBJECTIVE: We analyzed the outcome of patients with symptomatic vertebral
      hemangiomas treated at University of California, San Francisco, over a 20 year
      period. Treatment included transarterial embolization, embolization followed by
      surgical decompression or vertebral reconstruction with arthrodesis, and
      percutaneous vertebroplasty alone. METHODS: All medical, surgical, and
      radiological records were reviewed retrospectively. All patients underwent follow
      up neurological examination and evaluation of back pain. RESULTS: Sixteen
      patients diagnosed with symptomatic vertebral hemangiomas causing pain or
      neurological deficit were treated at University of California, San Francisco,
      between 1984 and 2004. Mean follow-up was 81 months. Seven of nine patients
      undergoing surgical decompression and tumor resection reported pain relief and
      demonstrated improvement in neurological deficit when present. Two patients had
      recurrent myelopathy: one was successfully treated with a second decompressive
      surgery, whereas the second underwent a staged vertebrectomy. All three patients
      undergoing vertebrectomy had cord compression from extraosseous tumor growth.
      Preoperative embolization reduced expected intraoperative blood loss in four
      patients. Three of four patients who underwent transarterial embolization alone
      experienced resolution of back pain. Two of four patients treated with
      vertebroplasty had long-term pain relief. CONCLUSION: Transarterial embolization
      followed by laminectomy is a safe and effective procedure for the treatment of
      cord compression by vertebral hemangioma causing stenosis without instability or
      deformity. Vertebrectomy preceded by embolization and followed by reconstruction
      can be used to treat cord compression from extraosseous tumor extension.
      Transarterial embolization without decompression is an effective treatment for
      painful intraosseous hemangiomas. Vertebroplasty is useful for improving pain
      symptoms, especially when vertebral body compression fracture has occurred in
      patients without neurological deficit, but is less effective in providing long
      term pain relief.

PMID- 16462483
TI  - Randomized, prospective study comparing ulnar neurolysis in situ with submuscular
      transposition.
AB  - OBJECTIVE: To help clarify the optimal surgical strategy for idiopathic,
      symptomatic ulnar nerve compression at the elbow in terms of overall outcome and
      morbidity by using objective criteria. METHODS: Forty-four surgical candidates
      were recruited prospectively and were randomized into the neurolysis (n = 23) or
      transposition (n = 21) arm of the study. Preoperative and postoperative outcomes
      were assessed symptomatically and by performance on McGowen and Louisiana State
      University Medical Center grading systems at 1 month, 6 months, and 1 year.
      RESULTS: Both procedures were equally effective in producing objective
      neurological improvement (61% in the neurolysis group, 67% in the transposition
      group). Wound complications, however, were more significant in the transposition
      group. Three of 21 in the transposition group compared with 0 of 23 in the
      neurolysis group experienced a deep wound infection. CONCLUSION: Idiopathic
      symptomatic ulnar nerve compression at the elbow is adequately treated by both
      neurolysis in situ and submuscular transposition. Submuscular transposition was
      associated with a higher incidence of complications. The authors therefore
      suggest the simpler procedure of neurolysis in situ as the treatment of choice.
      Submuscular transposition remains appropriate in certain circumstances.

PMID- 16462484
TI  - Racial differences in cerebral vasospasm: a systematic review of the literature.
AB  - OBJECTIVE: Despite a significant body of clinical research and the widespread use
      of early intervention with aggressive postoperative management, cerebral
      vasospasm (CV) continues to contribute significantly to the morbidity and
      mortality of aneurysmal subarachnoid hemorrhage (aSAH). Many studies have
      evaluated predictive factors, although none to date has investigated a possible
      difference in the incidence of CV between Asian and white patients. We present a
      review of the modern aSAH literature to examine the incidence of CV in Japan and
      Europe, two highly researched populations. METHODS: A literature search was
      performed using the Medline and PubMed databases. Studies conducted in Japan or
      Europe published between 1990 and 2004 that reported an incidence of CV after
      aSAH were subjected to a thorough review. Data from included studies were
      categorized by origin (Japan or Europe) and method of CV diagnosis (angiography,
      delayed ischemic neurological deficit, or new infarct attributable to CV), and
      then were combined. Recorded incidences then were compared using a chi test, and
      estimates of the relative risk of vasospasm were computed. RESULTS: The initial
      literature search identified 102 studies, and 32 studies met all inclusion
      criteria. The incidence of vasospasm diagnosed by angiography, delayed ischemic
      neurological deficit, and computed tomography was significantly greater in
      Japanese studies (all P < 0.001). The relative risks for Japanese patients as
      compared with European patients were 2.04, 2.07, and 1.53 for angiographic CV,
      delayed ischemic neurological deficit, and new infarct, respectively. CONCLUSION:
      Patients in Japanese studies were more likely to experience CV after aSAH across
      diagnostic methods. This may be a manifestation of genetic differences between
      Japanese and European populations. Clinicians should consider possible patient
      differences when interpreting CV research conducted in these populations.

PMID- 16462485
TI  - Endoscopic microneurosurgery: usefulness and cost-effectiveness in the
      consecutive experience of 210 patients.
AB  - OBJECTIVE: Indications, usefulness, and cost-effectiveness of the endoscope in
      routine microneurosurgery are not clear. To delineate such aspects, we assessed
      our experience of endoscopic application and additional cost to use an endoscope.
      METHODS: Endoscopes were used in 210 patients with cranial base and cisternal
      pathological features in the previous 7 years. Lesions were located in the
      extradural cranial base in 78 patients and in the cistern in 132 patients. Rigid
      lens endoscopes 2.7 to 4 mm in width, 11 to 20 cm in length, and 0 to 70 degrees
      in angle were used. RESULTS: Endoscopes were used for primary or a significant
      part of the surgery in 64% of the extradural cranial base procedures. Although
      endoscopes were used only for visual assistance in 82% of cisternal pathological
      features, significant benefit was noted in 9% and was not different from cranial
      base lesions. Eleven patients may have had complications if the endoscope had not
      been used, and 10 procedures would have been impossible without endoscopic use.
      Therefore, the number of patients need to treat to experience significant
      benefits by endoscope was 10. Endoscopic equipment costs an additional 326 US
      dollars per patient and, hence, significant benefit was the equivalent of 3260 US
      dollars. No permanent complications resulted from the use of the endoscope.
      CONCLUSION: The endoscope can be applied safely in routine microsurgery with
      specific equipment and has proven useful in 1 of 10 patients. To perform more
      effective procedures using endoscopes, we need to develop specially designed
      instruments usable through a narrow corridor and in an angled field.

PMID- 16462486
TI  - Cavernous malformations of the brainstem: three-dimensional-constructive
      interference in steady-state magnetic resonance imaging for improvement of
      surgical approach and clinical results.
AB  - OBJECTIVE: The indications for resection of cavernous malformations (CMs) of the
      brainstem include neurological deficits, (recurrent) hemorrhage, and surgically
      accessible location. In particular, knowledge of the thickness of the parenchymal
      layer and of the CM's spatial relation to nuclei, tracts, cranial nerves, and
      vessels is critical for planning the surgical approach. We reviewed the operative
      treatment of 13 patients with 14 brainstem CMs, with special regard to refined
      three-dimensional (3D)-constructive interference in steady-state (CISS) magnetic
      resonance imaging (MRI). METHODS: Patients were evaluated neurologically and by
      conventional spin-echo/fast spin-echo and 3D-CISS MRI. Surgery was performed with
      the use of microsurgical techniques and neurophysiological monitoring. RESULTS:
      Eleven CMs were located in the pons/pontomedullary region; 10 of the 11 were
      operated on via the lateral suboccipital approach. Three CMs were located near
      the floor of the fourth ventricle and operated on via the median suboccipital
      approach, with total removal of all CMs. Results were excellent or good in 10
      patients; one patient transiently required tracheostomy, and two patients
      developed new hemipareses/ataxia with subsequent improvement. Not only did 3D
      CISS sequences allow improved judgment of the thickness of the parenchymal layer
      over the lesion compared with spin-echo/fast spin-echo MRI, but 3D-CISS imaging
      also proved particularly superior in demonstrating the spatial relation of the
      lesion to fairly "safe" entry zones (e.g., between the trigeminal nerve and the
      VIIth and VIIIth nerve groups) by displaying the cranial nerves and vessels
      within the cerebellopontine cistern more precisely. CONCLUSION: Surgical
      treatment of brainstem CMs is recommended in symptomatic patients. Especially in
      patients with lesions situated ventrolaterally, the 3D-CISS sequence seems to be
      a valuable method for identifying the CM's relation to safe entry zones, thereby
      facilitating the surgical approach.

PMID- 16462487
TI  - Early experience with 3-T magnetic resonance tractography in the surgery of
      cerebral arteriovenous malformations in and around the visual pathway.
AB  - OBJECTIVE: To evaluate of the role of magnetic resonance (MR) tractography on the
      optic radiation with a 3-T MR unit in the surgery of cerebral arteriovenous
      malformation (AVM) in and around the visual pathway. METHODS: Of the 322 patients
      with cerebral AVMs admitted to our clinic between 1978 and 2005, a study of MR
      tractography was made on 29 patients. Ten of those patients had AVMs in and
      around the visual pathway and were included in this study. There were two men and
      eight women ranging in age from 15 to 64 years (mean age, 34.5 +/- 14.8 yr). All
      of the patients underwent 3-T tractography of optic radiation (OR) and neuro
      ophthalmologic evaluation. Four of the 10 patients underwent surgical resection
      of the AVM. A postoperative 3-T MR study and a neuro-ophthalmologic evaluation
      was performed 1 month after surgery in most patients. RESULTS: The preoperative
      patients for whom tractography demonstrated a continuous bundle of OR from the
      medial temporal region to the primary visual cortex had minimal or no visual
      field loss, whereas the patients for whom the tractography did not show a
      continuous bundle of OR had significant visual loss. The patients for whom
      tractography in the postoperative study demonstrated a bundle of OR experienced
      no postoperative deterioration of the visual field loss, whereas the patients for
      whom tractography did not demonstrate a bundle of OR exhibited significant visual
      field loss. CONCLUSION: This technique is thought to be useful in confirming the
      integrity of and localizing deviated tract and in evaluating the surgical risk,
      especially for nonhemorrhagic AVMs in and around the visual pathways, taking some
      limitations of this method into consideration.

PMID- 16462488
TI  - High-resolution magnetic resonance imaging for detection of carotid plaques.
AB  - OBJECTIVE: We report our experience using high-resolution magnetic resonance
      imaging (MRI) to identify carotid plaques and also discuss these MRI findings
      while comparing them with carotid endarterectomy specimens. METHODS: Eighteen
      carotid plaques from 17 different patients were observed using plaque MRI. The
      patients included 14 men and 3 women, aged 53 to 75 years (mean, 68.6 yr). Eight
      patients experienced a stroke and four patients experienced transient ischemic
      attack. The remaining five patients did not experience any neurological symptoms.
      Two-dimensional time-of-flight (TOF) MR angiography; T1-weighted imaging; fat
      suppressed, cardiac gated, black-blood proton density imaging; and T2-weighted
      imaging were obtained with a 1.5-T MRI. RESULTS: Symptomatic plaques showed
      either vast or partially dotted high signals for each contrast. The high signal
      intensity on time-of-flight and T2-weighted imaging predicted the instability of
      the plaques (100% sensitivity and specificity). In particular, time-of-flight
      imaging predicted intraplaque hemorrhaging with 100% sensitivity and 80%
      specificity. MRI revealed that three of four asymptomatic lesions were unstable
      plaques. CONCLUSION: High-resolution MRI was able to detect various signal
      patterns related to the plaque components, and it was thus considered to be very
      useful for evaluating plaque instability. The application of plaque MRI therefore
      may positively affect the decision-making process when selecting optimal
      therapeutic strategies to treat with carotid plaques.

PMID- 16462489
TI  - Increased expression of 5-lipoxygenase in high-grade astrocytomas.
AB  - OBJECTIVE: 5-Lipoxygenase (5-LO) oxidizes arachidonic acid into proinflammatory
      eicosanoids that may promote tumorigenesis. In this study, we investigated
      whether 5-LO is expressed in human astrocytomas and what effect its expression
      may have on patient outcome. METHODS: Increased 5-LO messenger ribonucleic acid
      and protein expression was detected by the polymerase chain reaction and antibody
      based approaches, respectively, in surgical astrocytoma specimens and established
      glioblastoma multiforme cell lines compared with primary cell culture from the
      human white matter. RESULTS: Immunohistochemical analysis revealed predominantly
      nuclear 5-LO staining in 44 of 49 glioblastoma multiforme samples (90%), 8 of 10
      (80%) anaplastic astrocytomas samples, and 3 of 13 (23%) low-grade astrocytoma
      samples analyzed. Double-staining experiments with anti-CD-68
      (macrophage/microglial marker) and anti-5-LO antibodies suggest that both CD-68
      positive and CD-68-negative tumor cells express 5-LO protein. Staining of 5-LO
      was significantly more frequent in high-grade than in low-grade tumors (P =
      0.001). Patients whose tumors expressed 5-LO were significantly older, had lower
      preoperative Karnofsky performance scores and shorter survival than patients
      whose tumors did not express 5-LO. After adjusting for pathological diagnosis and
      age, respectively, neither Karnofsky performance score nor survival were
      significantly associated with 5-LO staining. CONCLUSION: These data indicate that
      5-LO is overexpressed in high-grade astrocytomas and supports the idea that
      eicosanoids may play a role in tumorigenesis of these brain tumors.

PMID- 16462490
TI  - Acceleration of aneurysm healing by hollow fiber enabling the controlled release
      of basic fibroblast growth factor.
AB  - OBJECTIVE: The objective of this study was to develop an embolization material of
      hollow fiber combined with gelatin hydrogel for the controlled release of basic
      fibroblast growth factor (bFGF). We examined feasibility of the material in
      embolization healing aneurysm by bFGF-induced tissue organization. METHODS: An
      aneurysm was prepared at the common carotid artery of 60 rabbits by the end-to
      side anastomosis of jugular venous pouch. The hollow fibers combined with or
      without 100 microg free bFGF or gelatin hydrogel incorporating 0, 10, 50, or 100
      microg bFGF were applied to the aneurysm. Tissue appearance or histological
      observation was performed 1, 2, 3, and 6 weeks after application to evaluate the
      area embolized by fibrous organization in the aneurysm and the neointima
      formation at the aneurysm orifice. RESULTS: When applied with the hollow fibers
      combined with gelatin hydrogel containing 100 microg bFGF, the aneurysm was
      histologically occupied by fibrous tissue newly formed 3 weeks later, whereas
      neointima was formed at the aneurysm orifice. The histological area occupied by
      fibrous tissue was significantly larger than that of hollow fibers combined with
      100 microg bFGF. No influence of bFGF dose on the aneurysm healing by the fibers
      combined with hydrogels incorporating bFGF was observed. CONCLUSION: Local,
      controlled release of bFGF from the hollow fibers combined with gelatin hydrogel
      incorporating bFGF accelerated the aneurysm healing by tissue organization.

PMID- 16462491
TI  - Noninvasive bioluminescence imaging of luciferase expressing intracranial U87
      xenografts: correlation with magnetic resonance imaging determined tumor volume
      and longitudinal use in assessing tumor growth and antiangiogenic treatment
      effect.
AB  - OBJECTIVE: Outcome studies in rodent tumor models rely on both histological and
      noninvasive study end points. Intracranial models require special tools to
      observe tumor growth over time noninvasively, such as magnetic resonance imaging
      (MRI), computed tomographic scanning, or cranial window techniques. These
      techniques share disadvantages in terms of cost, technical expertise required,
      and overall animal throughput for analysis. In this report, we sought to validate
      the use of the relatively newer technique of bioluminescence imaging (BLI) of
      intracranial glioblastoma xenograft growth by comparing it with gadolinium
      enhanced MRI. METHODS: U87MG glioma cell lines genetically engineered to express
      the firefly luciferase gene were stereotactically injected into nude mice in the
      left frontal lobe. Weekly BLI and MRI were performed after the inoculation of
      tumor cells. For BLI, tumor growth was assessed as the peak BLI after systemic
      injection of luciferin substrate. MRI-based growth curves were created by three
      dimensional volumetric reconstruction of axial gadolinium-enhanced MRI data
      covering the whole brain. In a separate experiment, mice were treated with
      adenoviruses encoding antiangiogenic soluble vascular endothelial growth factor
      receptors, and treatment effect was monitored by BLI. RESULTS: Untreated tumor
      growth was readily detected and observed over time by serial BLI measurements.
      Furthermore, tumor-derived light emission was highly correlated with volume of
      tumor as assessed by MRI. Furthermore, the tested antiangiogenic treatment effect
      was readily detected using this technique, suggesting the power of the technique
      for sensitive monitoring of novel therapeutics. CONCLUSION: BLI offers a simple
      and rapid technique for assessing intracranial glioblastoma growth in rodent
      models noninvasively, which correlates well with MRI. The speed of the BLI
      technique can increase experimental throughput, allows for targeted histological
      analysis in animals showing the greatest treatment effects, and provides new
      insights into the kinetics of intracranial tumor growth in the setting of
      different treatments.

PMID- 16462492
TI  - Bone morphogenetic protein gene therapy using a fibrin scaffold for a rabbit
      spinal-fusion experiment.
AB  - OBJECTIVE: To observe the feasibility of using fibrin gel as a scaffold during
      rabbit spinal fusion with rat kidney cells carrying bone morphogenetic protein-2
      (BMP-2) expression vector. METHODS: Normal Rattusnorvegicus (rat) kidney (NRK)
      cells were transfected with pCMV-BMP2 vectors by using a nonviral reagent
      (FuGENE6), following which the transfected cells (1.5 x 10(7)) were encapsulated
      and evenly suspended in a fibrin scaffold, and implanted to either side of the L5
      L6 intertransverse space for six test rabbits. For the control group (six
      rabbits), the transfected cells (1.5 x 10(7)) were added on and absorbed in a
      surgical gelatin sponge, and implanted in an analogous location. Radiographs of
      the spine of all animals were taken at six, ten, and 12 weeks subsequent to
      fusion surgery. Gross and histological examination of the fusion masses for all
      the animals were performed subsequent to animals having been sacrificed at 12
      weeks. RESULTS: Expression of BMP-2 was verified in the pCMV-BMP2 transfected NRK
      cells which were used for the subsequent rabbit experiment. For all 12 rabbits,
      no evidence of implanted-tissue rejection was seen during the postoperative
      course. Neither residual scaffold nor inflammatory granulation tissue was seen in
      the harvested spinal segments. For the six study-group rabbits, radiographic
      examinations revealed that four individuals (67%) featured prominent new-bone
      formation (good fusion), and two (33%) revealed moderate new-bone formation (fair
      fusion) at the implanted sites, whereas all six control-group rabbits revealed no
      evidence of new-bone formation (nonfusion) at the implanted sites. For the
      histological examinations, all animals in the study group revealed the presence
      of osseous tissue at the sites corresponding to the sites of radiographically
      demonstrated new-bone formation, whereas for the control group, no osseous tissue
      was seen at the implanted sites for any animal CONCLUSION: Fibrin gel, being a
      biocompatible and biodegradable matrix, can encapsulate pCMV-BMP2 transfected NRK
      cells and adhere to the intertransverse lumbar-spine spaces of test rabbits. With
      the above characteristics, it plays an important role in the successful delivery
      of pCMV-BMP2-transfected cells for this rabbit spinal-fusion experiment. Being a
      natural matrix and able to be obtained readily from patients' own blood, fibrin
      gel seems to be a promising scaffold for future gene therapy in human trials.

PMID- 16462495
TI  - Tolerance of endorectal balloon in 396 patients treated with intensity-modulated
      radiation therapy (IMRT) for prostate cancer.
AB  - PURPOSE: To report patient tolerance and acute anorectal toxicity of an
      endorectal balloon used for prostate immobilization during 35 daily fractions.
      MATERIALS AND METHODS: The records of 396 patients treated for prostate cancer
      from October 1997 to November 2001 were reviewed. Patients were treated with
      intensity modulated radiation therapy (IMRT). Endorectal balloon catheter was
      inserted daily, inflated with 100 mL of air for immobilizing the prostate gland.
      Patient and treatment factors were analyzed. Patients received a mean dose of 77
      Gy/35 fractions/7 weeks with no rectal block. RESULTS: None of the 396 patients
      halted treatment because of associated ano-rectal toxicity. No patient stated
      that he would decline to be treated again with rectal balloon. Three of 396
      (0.8%) patients required a reduction in the volume of the balloon to 50 mL.
      Seventeen of 396 (4.3%) patients required Lidocaine jelly with the insertion of
      balloon. Radiation Therapy Oncology Group (RTOG) grades 1 and 2 rectal toxicity
      occurred in 55/396 (13.9%) and 73/396 (18.4%), respectively. No RTOG grade 3 or 4
      toxicities occurred. Topical anal medications were prescribed for 46 of 396
      (11.6%) patients and antidiarrhea medication for 27 of 396 (6.8%) patients. Of
      patients with pretreatment anorectal disease, 50% developed rectal toxicities
      over the 7 weeks. Rectal toxicity occurred most frequently in the third, fourth,
      fifth, or sixth week; 19.5%, 20.8%, 18.2%, and 16.9%, respectively. The duration
      of the toxicity measured lasted 1 week, 35.2%; 2 weeks, 31.0%; 3 weeks, 15.5%; 4
      weeks, 11.3%; 5 weeks, 4.2%; and 6 weeks, 2.8%. CONCLUSION: Most of the patients,
      393/396 (99.2%), tolerated a 100 mL endorectal immobilization balloon for IMRT.
      The rate of acute anorectal toxicity was acceptable with no grade 3 or 4
      toxicities. Duration of the toxicities typically was 1 to 2 weeks. Patients with
      pre-existing anorectal disease are at higher risk of developing acute anorectal
      toxicity with the use of an endorectal balloon.

PMID- 16462494
TI  - A phase I dose finding study of cisplatin, gemcitabine, and weekly docetaxel for
      patients with advanced transitional cell cancer.
AB  - OBJECTIVE: Efficacious regimens are needed for the treatment of metastatic
      bladder cancer. The aim of this study was to determine the toxicity and phase II
      dose of a triplet regimen of cisplatin, gemcitabine, and weekly docetaxel for
      patients with advanced transitional cell carcinoma. METHODS: Thirteen patients
      were enrolled to the study: 3 to dose level 1 (cisplatin 70 mg/m2 on day 1;
      gemcitabine 1000 mg/m2, day 1 and 8; and docetaxel 30 mg/m2, day 1 and 8, every
      21 days), and 10 to dose level -1 (cisplatin 70 mg/m2 on day 1; gemcitabine 800
      mg/m2, day 1 and 8; and docetaxel 30 mg/m2, day 1 and 8, every 21 days). RESULTS:
      Grade 3-4 hematologic toxicities included neutropenia (40%) and thrombocytopenia
      (20%). Grade 3 nonhematologic toxicity was restricted to diarrhea. There were 2
      early deaths: 1 from a suspected pulmonary embolism and another from sepsis. In
      11 patients who received > or =2 cycles the response rate was 73%. CONCLUSIONS:
      The recommended phase II dose of this triplet regimen in advanced transitional
      cell carcinoma is cisplatin 70 mg/m2 on day 1; gemcitabine 800 mg/m2 day 1 and 8;
      and docetaxel 30 mg/m2 day 1 and 8, repeated every 21 days. The preliminary
      objective response rate was high in this cohort of patients.

PMID- 16462496
TI  - Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors
      expressing KIT.
AB  - OBJECTIVE: This phase II study was conducted to determine the activity of
      imatinib (gleevec) in heavily pretreated patients with KIT-positive metastatic
      germ cell tumor. MATERIALS AND METHODS: From June 2002 through April 2005, 18
      patients with refractory germ cell tumors were tested for KIT expression by
      immunohistochemistry. All patients screened were deemed to be incurable with
      further standard chemotherapy or surgery. Six patients were eligible and treated
      with imatinib 600 mg/d orally. RESULTS: There were no complete or partial
      remissions. Five of 6 patients had progressive disease and 1 patient had stable
      disease with a >50% decline in serum alpha-fetoprotein for 3 months before
      developing further progression. CONCLUSION: In this small sample size, there was
      no evidence of significant antitumor activity of imatinib in patients with KIT
      positive refractory germ cell tumors.

PMID- 16462497
TI  - Influence of number of CAG repeats on local control in the RTOG 86-10 protocol.
AB  - OBJECTIVES: The number of CAG repeats on the androgen receptor (AR) gene is
      inversely proportional to transcriptional activity. The purpose of this study was
      to determine if short-term androgen deprivation therapy (RT + HT) can improve
      outcome in patients with tumors with short CAG repeats (<19). MATERIALS AND
      METHODS: Prostate cancer patients were randomized to receive either radiotherapy
      (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94
      tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases.
      AR flow cytometry measurements were done on 13 patients. The effect on local
      failure (LF), distant metastases (DM), prostate cancer survival (PSS), and
      overall survival (OS) was studied. RESULTS: Pretreatment characteristics and
      assigned treatment arm were not significantly different between the parent and
      test groups except for a significantly higher risk of death (P = 0.049) in the
      test group. The median CAG repeat was 19. There were no significant differences
      in stage, or Gleason score between high (19 or greater) and low CAG (<19)
      patients within each treatment group. Number of CAG repeats alone did not
      significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome
      was studied in conjunction with androgen deprivation therapy, patients with CAG
      <19 who received H + RT had improved local control as compared with patients who
      received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local
      control over patients with CAG > or =19 that received H + RT (P = 0.028).
      CONCLUSIONS: Patients with short CAG repeats show a local control benefit with
      short-term androgen deprivation therapy, but no improvement in survival.

PMID- 16462498
TI  - Examining time intervals between diagnosis and treatment in the management of
      patients with limited stage small cell lung cancer.
AB  - OBJECTIVE: To examine time intervals between diagnosis and treatment of limited
      stage small cell lung cancer (L-SCLC) and to evaluate its effect on clinical
      outcomes. MATERIALS AND METHODS: Data on 166 patients with L-SCLC referred to a
      regional cancer center between January 1991 and December 1999 were analyzed. The
      time intervals studied were defined as: interval A, first abnormal chest x-ray to
      pathologic diagnosis: interval B, diagnosis to first oncology consultation;
      interval C, oncology consultation to first day of thoracic radiotherapy (RT);
      interval D, oncology consultation to first day of chemotherapy; and interval E,
      first day of chemo to first day of RT. Cox proportional hazards models were used
      to examine associations between the time intervals and thoracic relapse (TR) and
      overall survival (OS) outcomes. Logistic regression analysis was used to model
      associations between time and complete response (CR) rates. RESULTS: The median
      time duration of intervals A to E were 20, 12, 63.5, 15, and 48 days,
      respectively. When time was analyzed as a continuous variable, no statistically
      significant association between the interval lengths and outcomes studied was
      observed. Dichotomizing each interval using the median value as cut-off revealed
      that interval A >20 days was significantly associated with improved CR (odds
      ratio = 3.573; P = 0.027) whereas interval B >12 days was associated with a trend
      toward lower CR (odds ratio = 0.348; P = 0.073). CONCLUSIONS: Short median times
      from first abnormal chest x-ray to diagnosis and from diagnosis to oncology
      consultation indicate that L-SCLC patients were diagnosed and referred promptly
      in the community setting. OS and TR appeared independent of the time intervals
      analyzed. Individual variations in disease presentation and tumor biology may
      explain the observed associations between early pathologic diagnosis and inferior
      CR rates.

PMID- 16462499
TI  - Sinonasal undifferentiated carcinoma.
AB  - PURPOSE: The purpose of this paper is to discuss the treatment and outcomes for
      patients with sinonasal undifferentiated carcinoma. METHODS: Review of the
      pertinent literature. RESULTS: Most series contain a limited number of patients
      treated with various combinations of surgery, radiotherapy (RT), and
      chemotherapy. Follow-up periods for disease-free patients are sometimes
      relatively short. The majority of patients present with locally advanced tumors;
      10% to 30% have clinically positive regional nodes. The risk of local-regional
      recurrence after treatment is probably 20% to 30% or higher, depending on the
      extent of disease. The likelihood of distant dissemination is approximately 25%
      to 30% and the cure rate varies from roughly 20% to 50%. Better outcomes are
      observed in patients treated with craniofacial resection combined with pre- or
      postoperative RT alone or with adjuvant chemotherapy. This is probably due, in
      part, to selection bias. Patients with incompletely resectable tumors are best
      treated with definitive RT and adjuvant chemotherapy. CONCLUSION: The optimal
      treatment is craniofacial resection combined with adjuvant RT alone or with
      chemotherapy. The risk of relapse is relatively high and the probability of cure
      is modest. Patients with incompletely resectable tumors may sometimes be cured
      with definitive chemoradiation.

PMID- 16462500
TI  - Definitive radiotherapy for squamous cell carcinoma of the base of tongue.
AB  - OBJECTIVE: To evaluate definitive radiotherapy (RT) for treatment of base of
      tongue cancer. METHODS: There were 333 patients with squamous cell carcinoma of
      the base of tongue treated with definitive RT and had follow-up from 0.2 to 26.2
      years. Follow-up on living patients ranged from 1.2 to 26.2 years (median, 6.6
      years). RESULTS: Local control rates at 5 years were: T1, 98%; T2, 92%; T3, 82%;
      and T4, 53%. The 5-year rates of local-regional control rates were: I-II, 100%;
      III, 82%; IVA, 87%; and IVB, 58%. The rates of absolute and cause-specific
      survival at 5 years were as follows: I-II, 67% and 91%; III, 66% and 77%; IVA,
      67% and 84%; and IVB, 33% and 45%. Severe complications developed in 52 patients
      (16%). CONCLUSION: Our data and review of the pertinent literature reveal that
      the local-regional control rates and survival rates after RT were comparable to
      those after surgery, and the morbidity associated with RT was less.

PMID- 16462501
TI  - The combination of capecitabine and thalidomide in previously treated, refractory
      metastatic colorectal cancer.
AB  - BACKGROUND: With the increasing survival of patients with metastatic colorectal
      cancer (CRC) there is a growing need for effective second- and third-line agents.
      We conducted a multicenter, phase II study to examine the combination of
      capecitabine and thalidomide (Cape/Thal) in patients with refractory metastatic
      CRC. METHODS: Patients with previously treated stage IV CRC were eligible.
      Treatment consisted of capecitabine at 1,000 mg/m2 po BID for 14 days every 3
      weeks and thalidomide, starting at 200 mg po QD continuously. Thalidomide was
      escalated individually to 600 mg po QD as tolerated. We analyzed overall survival
      (OS), progression-free survival, response, and toxicity rates. RESULTS: Thirty
      four eligible patients were enrolled. The median age was 57 years, and most
      patients had a normal performance status (65%). All patients had received prior
      chemotherapy and 19 (56%) had received 2 or 3 prior regimens. The median number
      of Cape/Thal cycles administered was 3 (range, 1-15). Grade 3/4 toxicities
      included fatigue (15%), venous thromboembolic events (12%), somnolence (12%), and
      constipation (9%). Grade 2 hand-foot syndrome occurred in 5 (15%) patients. There
      were no radiographic responses; 13 patients (38%) achieved stable disease. The
      median PFS was 2.6 months (95% confidence interval [CI] = 2.2-3.9) and the median
      OS was 7.1 month (95% CI = 5.2-12.0). CONCLUSIONS: Though well-tolerated, the
      combination of capecitabine and thalidomide was not associated with objective
      tumor responses in a population of patients with previously treated metastatic
      CRC.

PMID- 16462502
TI  - Irinotecan, oxaliplatin plus bolus 5-fluorouracil and low dose folinic acid every
      2 weeks: a feasibility study in metastatic colorectal cancer patients.
AB  - OBJECTIVES: Irinotecan or oxaliplatin combined with 5-fluorouracil (5-FU) +/-
      folinic acid (FA) has changed the treatment standards for metastatic colorectal
      cancer (CRC). The oxaliplatin and irinotecan combination has reported consistent
      activity. The purpose of this phase II study was to assess the efficacy and
      safety of the simultaneous administration of a triple chemotherapy combination of
      oxaliplatin, irinotecan, 5-FU bolus, and FA. MATERIALS AND METHODS: Eligible
      patients had metastatic CRC with no prior oxaliplatin or irinotecan-based
      chemotherapy. Treatment consisted of oxaliplatin 85 mg/m2 followed by irinotecan
      150 mg/m2, repeated every 15 days, with 5-FU 500 mg/m2 bolus and FA 20 mg/m2 on
      days 1, 8, and 15. An early amendment suppressed the day 8 5-FU/FA. RESULTS:
      Twenty-six eligible treated patients receiving 253 doses were assessed for
      toxicity. Myelosuppression was the most frequent toxicity; grade 3 to 4
      neutropenia and febrile neutropenia occurred in 50% and 15% of patients,
      respectively. The treatment schedule modification, omitting the 5-FU dosing on
      day 8, considerably improved treatment compliance, reducing the incidence of
      febrile neutropenia, diarrhea, and asthenia. Among the 25 patients evaluable for
      efficacy, 10 had objective responses including 1 complete response (CR) (4%) and
      9 partial responses (PR) (36%), giving an overall response rate of 40%. Median
      time to progression was 6.20 months [95% confidence interval (CI), 5.44-6.96].
      Median overall survival was 12.95 months. CONCLUSIONS: The administration of a
      triple combination produced promising objective responses with acceptable
      toxicity but does not seem to produce an evident benefit in time-related
      parameters.

PMID- 16462503
TI  - Will improvement in quality of life (QOL) impact fatigue in patients receiving
      radiation therapy for advanced cancer?
AB  - BACKGROUND: Fatigue has a significant impact on the quality of life (QOL) of
      cancer patients. Recent research has suggested that physical activity can reduce
      fatigue in patients receiving active cancer treatment. In this project, we
      examined the impact that participation in a randomized controlled trial of a
      multidisciplinary intervention designed to impact overall QOL had on fatigue for
      advanced cancer patients actively receiving treatment. METHODS: Patients with
      newly diagnosed cancer were randomly assigned to an 8-session structured
      multidisciplinary intervention or a standard-care arm at the beginning of their
      course of radiotherapy (RT) designed to impact QOL. Ninety-minute sessions were
      led by either a psychiatrist or psychologist, collaborating with a nurse,
      physical therapist, chaplain, or social worker, depending on the session's theme.
      The fatigue assessments used in this trial included the Linear Analogue Self
      Assessment (LASA), the Profile of Mood States (POMS), Spielberger's State-Trait
      Anxiety Inventory (STAI), and the Symptom Distress Scale (SDS). RESULTS: There
      were 115 participants enrolled and the 2 randomization arms were well balanced in
      terms of baseline characteristics and treatment received except for increased
      commuting distance for the patients in the intervention arm (P = 0.042). Most of
      scores indicated less fatigue (higher score) in the standard treatment group, but
      there were no statistically significant differences found at baseline and weeks
      4, 8, and 27 except for SDS at week 8 (P = 0.018) with less patients reporting
      significant fatigue in the standard treatment arm. For the entire participant
      population, fatigue levels initially worsened with radiotherapy, stabilized at
      week 8, and returned to baseline by week 27. Disease site, chemotherapy use, and
      radiotherapy dose did not have a significant impact on fatigue levels.
      CONCLUSIONS: Radiotherapy initially caused a worsening of fatigue but with time
      fatigue levels returned to baseline. Clinically, this structured
      multidisciplinary intervention had no impact on fatigue, and there was the
      suggestion the multiple sessions may have contributed to worse fatigue during
      active cancer treatment.

PMID- 16462504
TI  - Phase II trial of gemcitabine as first line chemotherapy in patients with
      metastatic or unresectable soft tissue sarcoma.
AB  - OBJECTIVE: The availability of effective chemotherapy agents or regimens for soft
      tissue sarcomas (STS) is limited. Response to available first line regimens is
      generally poor and response to second line regimens is rare. Considering the poor
      response of STS to available cytotoxic therapy, and the need to adequately
      evaluate the effectiveness of new agents, first line investigation of promising
      new agents is justified. Gemcitabine, a relatively new agent, has demonstrated
      effectiveness in several solid tumors. Limited clinical trials have suggested
      modest activity in STS. A multi-institutional study of gemcitabine in patients
      with STS, without prior chemotherapy for metastatic disease, was initiated in the
      Southwest Oncology Group May 1, 1998 and completed March 15, 1999. MATERIALS AND
      METHODS: Patients were required to have metastatic or unresectable STS with no
      prior chemotherapy for metastatic disease. Gastrointestinal leiomyosarcomas and
      stromal tumors were not eligible. Patients were required to have a performance
      status of 0-2, measurable disease, adequate renal, hepatic, and hematologic
      function. The patients were given Gemcitabine 1000 mg/M2 iv over 30 minutes on
      days 1, 8, and 15, 22, 29, 36, 43, 57, 64, and 71. Dosage reduction was performed
      for cytopenias and/or other grade 3 or 4 toxicity. RESULTS: Forty-eight patients
      were registered to the study. The median age was 62 years (range, 30-80) with 21
      male and 25 female patients. Two patients were ineligible (1 GI stromal tumor and
      1 nerve sheath tumor). Forty-six patients are evaluable for response, toxicity,
      and survival. There were 2 treatment-related deaths (1 renal failure and 1
      hemolytic uremic syndrome). Six additional patients experienced grade 4 toxicity
      (3 neutropenia, 2 dyspnea, 1 vomiting, and 1 renal failure). Three of the 46
      eligible patients had a partial response (7%: 95% confidence interval 1-18%) and
      8 patients had stable disease (20%). Nine patients had inadequate assessments to
      define response. Forty-five patients have died with a median survival of 6 months
      (95% confidence interval 5-10 months). CONCLUSION: Gemcitabine has minimal
      activity as a single agent at this dose and schedule in advanced STS. The low
      response rate does not justify further investigation of gemcitabine as a single
      agent in STS.

PMID- 16462505
TI  - Adjuvant radiotherapy in the management of soft tissue sarcoma involving the
      distal extremities.
AB  - OBJECTIVE: Treating soft tissue sarcoma (STS) of the distal extremity is
      challenging in terms of achieving local control and avoiding complications. It is
      now accepted that a limb conserving approach provides equivalent survival when
      compared with radical amputation. METHODS: Twenty-three patients with STS
      involving the hand-wrist or foot-ankle complex received adjuvant radiotherapy
      (RT) for limb conservation and were evaluated to determine if local control,
      survival, and functional ability were achieved. The median patient age was 64 and
      median time of follow-up was 11 years. The location of the sarcoma included the
      hand (n = 12) or foot (n = 11). Seven patients received preoperative RT (median
      dose, 50.40 Gy) and 16 patients received postoperative RT (median dose, 64.80
      Gy). Patients treated preoperatively and 9 treated postoperatively received
      hyperfractionated RT at 1.2 Gy twice-daily. Seven patients treated
      postoperatively received conventional daily-fractionated treatment. RESULTS:
      Twenty of 23 patients received RT at first presentation; 3 were treated for
      locally recurrent disease. The 5- and 10-year rates of local control were 91%.
      The 10-year rates of cause-specific and absolute survival were 96% and 91%,
      respectively. The 5- and 10-year rates of distant metastases-free survival were
      87%. The ultimate limb-conservation rate was 91%. No patient required an
      amputation because of local recurrence or treatment complications. Function of
      the hand or foot was maintained for all of the 21 patients for whom limb
      conserving treatment was achieved. CONCLUSIONS: Combined modality therapy with
      limb-conserving surgery and adjuvant RT achieves excellent local control (91%)
      and potential overall survival (91%) rates with excellent functional outcome.

PMID- 16462506
TI  - Intensity modulated radiation therapy (IMRT) decreases acute skin toxicity for
      women receiving radiation for breast cancer.
AB  - OBJECTIVE: To determine the clinically observed incidence and severity of acute
      skin toxicity with breast intensity modulated radiation therapy (IMRT), and
      compare the results with a matched cohort of patients treated by conventional
      radiation therapy. Our hypothesis is that measures to decrease dose inhomogeneity
      within the breast and skin with IMRT will improve acute skin toxicity. MATERIALS
      AND METHODS: The study population consists of 73 women with early stage breast
      cancer treated with breast-conserving surgery and IMRT. The IMRT technique
      involves an iteration method for optimization to generate the IMRT plan, Monte
      Carlo dose calculation, and a step-and-shoot technique using multileaf
      collimation for beam delivery. Other aspects of the technique including the
      clinical definition of the clinical target volume by the physician, patient
      positioning, tangential beam orientation, dose and field sizes were unchanged
      compared conventional tangential radiation. These patients were matched one-to
      one to a control group of 60 women treated with conventional photon radiation by
      using their bra size and chest wall separation. The study end point was acute
      skin toxicity. RESULTS: There were no observed differences in the acute toxicity
      based upon common terminology criteria for adverse events (CTC) for acute
      radiation dermatitis. There was no desquamation in 42% of IMRT patients, dry
      desquamation in 37% and moist desquamation in 21%. The degree of desquamation was
      greater for conventional patients compared with IMRT patients -52% grade 0, 10%
      grade 1, and 38% grade 2 (P = 0.001). Subgroup analysis showed desquamation was
      significantly lower with IMRT for small (P = 0.038) and large breast sizes (P =
      0.037), but not medium sizes (P = 0.454). For large breast sizes, the incidence
      of moist desquamation grade 2 was 48% with IMRT compared with 79% in controls.
      Significant predictors of moist desquamation on stepwise logistic regression were
      use of IMRT (P = 0.0011) and breast size (P < 0.0001). CONCLUSIONS: IMRT is
      associated with a decrease in severity of acute desquamation compared with a
      matched control group treated with conventional radiation therapy. As with
      conventional radiation, breast size remains the most important prognostic factor
      for acute skin toxicity. The CTC grading system for acute radiation dermatitis is
      not sensitive when applied to modern breast cancer treatment because of its
      dependence of subjective rating of erythema and inability to gauge variations in
      desquamation. Further study of patient symptoms, quality of life, and cosmesis is
      needed to evaluate the benefit of IMRT for breast cancer.

PMID- 16462507
TI  - Impact of Her-2 Neu overexpression on outcome of elderly women treated with wide
      local excision and breast irradiation for early stage breast cancer: an
      exploratory analysis.
AB  - OBJECTIVE: The purpose of this study was to investigate the prognostic
      significance of Her-2 neu status in elderly patients managed with breast
      conservation strategy for stage I-II breast cancer. METHODS: We conducted an IRB
      approved retrospective review of 153 women age 70 and older with stage I-II
      breast cancer, managed with wide local excision and breast radiation between
      January 1997 and December 2002. The subset of 106 patients had a known Her-2 neu
      status and was analyzed for primary patient and tumor characteristics. These
      characteristics were correlated with cause specific survival (CSS), overall
      survival (OS), and combined nodal and distant failure (NDF). Her-2 neu positivity
      was confirmed with FISH HercepTestTM. Statistical tests included Cox regression,
      contingency table and Kaplan-Meier analysis. RESULTS: Median follow-up was 55
      months and patient's median age was 76. Twenty two percent of patients were Her-2
      neu positive and 78% were Her-2 neu negative. Her-2 neu positivity was
      significantly associated with high histologic grade (P = 0.008), T2 stage (P =
      0.001) and positive axillary lymph nodes (P = 0.02) among 73 patients who had
      surgical assessment of axilla. Overall, only 15 patients (14%) received
      chemotherapy. There were no recurrences in the breast. Her-2 neu positivity
      predicted for NDF and CSS on multivariate analysis. Projected 5-year freedom from
      NDF was 70% for Her-2 neu positive and 97% for Her-2 neu negative patients (P <
      0.01, log-rank). CSS was 86% for Her-2 neu positive and 98% for Her-2 neu
      negative patients (P < 0.01, log-rank). OS was no different between Her-2 neu
      positive and Her-2 neu negative patients (80% versus 85%, P = 0.25). CONCLUSIONS:
      Her-2 neu amplification predicts development of NDF and negatively influences
      CSS, but not local control or OS in elderly patients treated with breast
      conservation. Similar to the trend in younger patients, Her-2 neu positivity may
      be used in the future to consider more aggressive treatment strategies in elderly
      patients.

PMID- 16462508
TI  - Does breast size affect the scatter dose to the ipsilateral lung, heart, or
      contralateral breast in primary breast irradiation using intensity-modulated
      radiation therapy (IMRT)?
AB  - PURPOSE: To evaluate the relationship between the primary breast volume and dose
      received by the ipsilateral lung, heart (for left-breast cancers), and
      contralateral breast during primary breast irradiation using intensity-modulated
      radiation therapy (IMRT). METHODS AND MATERIALS: Sixty-five patients with breast
      carcinoma were treated using 6-MV photons with IMRT technique using the Eclipse
      Planning System following breast conserving surgery. All patients had a treatment
      planning CT scan. The primary breast, ipsilateral lung, and heart were contoured
      on the axial CT slices. The primary breast volume was calculated using the
      Eclipse Planning System. The mean ipsilateral lung and heart doses were obtained
      from the dose-volume histogram. The contralateral breast dose was measured using
      paired thermoluminescent dosimeters (TLDs) placed on the patient's contralateral
      breast, 4 cm from the center of the medial border of the primary breast
      irradiation field. RESULTS: The mean dose delivered with photons to the primary
      breast for all patients was 49.97 Gy. The mean volume of the primary irradiated
      breast was 1167.9 cc. As a percentage, the mean ipsilateral lung, heart, and
      contralateral breast doses were 11.2%, 6.1%, and 7.2%, respectively. The primary
      breast volume positively correlated with the contralateral breast dose (P <
      0.0005). There was no significant correlation between the breast volume and the
      ipsilateral lung or heart dose (P = 0.463 and 0.943, respectively). CONCLUSION:
      This study suggests that the primary breast size significantly affects the
      scatter dose to the contralateral breast but not the ipsilateral lung or heart
      dose when using IMRT for breast irradiation.

PMID- 16462509
TI  - Capecitabine plus weekly oxaliplatin in gastrointestinal tumors: a phase I study.
AB  - OBJECTIVE: To investigate the maximum tolerated dose (MTD) and the dose-limiting
      toxicity (DLT) of capecitabine plus oxaliplatin. MATERIALS AND METHODS:
      Oxaliplatin was given by 2-hour iv infusion on days 1 and 8, and capecitabine was
      given orally, from day 1 to 14, every 3 weeks. We tested 4 levels of doses: 1)
      capecitabine 1650 mg/m2 + oxaliplatin 50 mg/m2; 2) capecitabine 2000 mg/m2 +
      oxaliplatin 50 mg/m2; 3) capecitabine 2000 mg/m2 + oxaliplatin 60 mg/m2; and 4)
      capecitabine 2500 mg/m2 + oxaliplatin 60 mg/m2. Patients with gastrointestinal
      neoplasm were eligible for the study. RESULTS: Thirty-two patients were enrolled.
      At dose level 4, 3 patients had unacceptable toxicity (grade 3 diarrhea, grade 4
      diarrhea, and grade 3 mucositis, respectively), thus, level 4 was the MTD. Apart
      from DLT, overall toxicity was mild: grade > or =3 nonhematological toxicity
      occurred in 3 patients, and hematological toxicity was sporadic. CONCLUSION: This
      study demonstrates that clinically relevant doses of capecitabine (2000 mg/m2
      from day 1 to 14) plus oxaliplatin (60 mg/m2 on days 1 and 8) every 3 weeks can
      be given without causing unacceptable toxicity.

PMID- 16462510
TI  - Trastuzumab and antiestrogen therapy: focus on mechanisms of action and
      resistance.
AB  - OBJECTIVE: In breast cancer, 2 molecular targets are well established (ER/PR and
      HER2), and therapies directed to these proteins have demonstrated to be
      clinically useful. METHODS: Despite the presence of the ER and PR, only half of
      the patients will respond to endocrine therapy, and less than 35% of patients
      with ErbB2-overexpressing metastatic breast cancer will respond to trastuzumab as
      a single agent. RESULTS: To improve survival of metastatic breast cancer patients
      with ER/PR positive and HER2 positive is critical to elucidate the mechanism of
      resistance or sensitivity of these tumors for a better selection depending on
      biologic molecular alterations. CONCLUSIONS: Recently, several studies addressing
      this issue have been reported. Here, we will focus on a comprehensive review of
      the currently available data.

PMID- 16462511
TI  - Giant cell tumor of bone.
AB  - OBJECTIVE: To discuss the treatment and outcomes for giant cell tumor (GCT) of
      bone. MATERIALS AND METHODS: Review of the pertinent literature. RESULTS: GCT is
      a rare benign bone lesion most often found in the extremities of women in the
      third and fourth decades of life. Surgery is the mainstay of treatment and
      usually consists of intralesional curettage; local control rates range from 80%
      to 90% after this procedure. Patients with extensive, recurrent, and/or
      biologically more aggressive tumors may require wide excision. A small subset of
      patients with incompletely resectable GCTs or with lesions that are surgically
      inaccessible may be treated with moderate-dose radiotherapy (45-50 Gy) and have a
      65% to 80% likelihood of being locally controlled. CONCLUSION: The majority of
      patients with GCTs are effectively treated with intralesional curettage. Wide
      excision or radiotherapy is necessary to cure a relatively limited subset of
      patients with extensive, aggressive, and/or incompletely resectable GCTs.

PMID- 16462512
TI  - Should we screen patients for inherited thrombophilia before starting
      thalidomide?
AB  - The authors present a case of refractory multiple myeloma in an elderly patient
      with heterozygosity for the G20210A mutation of factor II and for the C677T
      mutation of methylenetetrahydrofolate reductase. This patient developed acute,
      multiple cerebral infarctions 5 months into the treatment with thalidomide. The
      patient improved on oral anticoagulation. The authors presume that thalidomide
      increased the risk of cerebral infarction in this predisposed patient. The
      presence of increased risk for thrombosis should alert clinicians to screen
      patients presenting with systemic thrombosis for inherited thrombophilia. This
      risk increases with the presence of diseases and therapies that predispose for a
      hypercoagulable state. They suggest that patients required to be on thalidomide
      should be screened for inherited thrombophilia and should be considered for
      prophylactic anticoagulation therapy.

PMID- 16462513
TI  - Unusual manifestations of disseminated neoplasia at presentation: right-sided
      heart failure due to a massive cardiac metastasis and autoimmune thrombocytopenia
      in pleomorphic rhabdomyosarcoma of the adult.
AB  - Although it is recognized that aggressive soft tissue sarcomas may give rise to
      cardiac metastases, these manifestations are usually late and clinically silent,
      being the prevailing finding in exceptional cases. This report describes the
      occurrence of a massive cardiac metastasis at diagnosis of leg rhabdomyosarcoma
      in a middle-age adult. This manifestation was the cause of rapidly progressive
      congestive heart failure and, together with the unusual occurrence of autoimmune
      thrombocytopenia, led to difficult patient care with a significantly negative
      influence on the outcome.

PMID- 16462514
TI  - A case of synchronous lymphoplasmacytic lymphoma and rectal carcinoid.

PMID- 16462515
TI  - A case report of a recurrent intracranial ependymoma treated with temozolomide in
      remission 10 years after completing chemotherapy.

PMID- 16462517
TI  - Malignancy and autoimmunity.
AB  - PURPOSE OF REVIEW: The association of cancer with autoimmune disease has been
      under investigation for several years. Reports have appeared suggesting increased
      cancer risk in autoimmune rheumatic diseases. Evidence has been accumulating
      recently in rheumatoid arthritis, Sjogren's syndrome, systemic lupus
      erythematosus, and scleroderma/systemic sclerosis. This review focuses on recent
      publications regarding risk of cancer in these conditions. RECENT FINDINGS:
      Despite a lack of a strong association between rheumatoid arthritis and cancer
      overall, studies show an increased risk for the development of lymphoma in
      rheumatoid arthritis. There are data suggesting an increased risk for rheumatoid
      arthritis patients regarding lung cancer. In Sjogren's syndrome-related
      malignancies, most publications in the past year relate to non-Hodgkin's
      lymphomas, and suggest possible mechanisms driving the association. Data
      substantiate an increased risk of certain cancers in systemic lupus
      erythematosus; the risk appears to be most heightened for lymphoma. A recent
      cohort study examined cancer risk in scleroderma; the estimates were lower than
      previous studies had suggested, and the confidence intervals relatively
      imprecise, making a definitive conclusion difficult. SUMMARY: There have been
      several papers published related to cancer in the rheumatic diseases,
      particularly inflammatory arthritis, Sjogren's syndrome, systemic lupus
      erythematosus, and scleroderma/systemic sclerosis. Continuing interest in the
      association between autoimmune rheumatic diseases and malignancy is likely, given
      the potential impact in terms of understanding both rheumatic diseases and
      cancer.

PMID- 16462518
TI  - The cardiovascular manifestations of rheumatic diseases.
AB  - PURPOSE OF REVIEW: To review the cardiovascular manifestations of several more
      common rheumatic conditions in the light of the recent reported literature.
      RECENT FINDINGS: Evidence that chronic inflammation is associated with the
      occurrence of cardiac events in people both with and without chronic inflammatory
      joint disease is emerging. Both atherosclerosis and rheumatic diseases, however,
      have a complicated cause, and it is likely that inflammation contributes to other
      environmental and host risk factors in these patients. Treatments used to
      suppress inflammation in many rheumatic conditions have the potential to reduce
      cardiovascular disease morbidity as well as improve musculoskeletal function.
      SUMMARY: Cardiovascular morbidity and mortality have been found to be increased
      in association with many of the rheumatic diseases. In particular, coronary heart
      disease seems to be associated with inflammatory rheumatic conditions. Whilst it
      is likely that chronic systemic inflammation promotes accelerated atherosclerosis
      in these patients, the mechanisms by which this occurs are complex and the
      effects of treatment and other cardiovascular risk factors need to be considered.

PMID- 16462520
TI  - Epidemiology of osteoarthritis: an update.
AB  - PURPOSE OF REVIEW: As the most common arthritis and a leading cause of chronic
      disability, osteoarthritis is associated with substantial cost to the individual
      and to society. Epidemiologic studies have supplied, in addition to incidence,
      prevalence and risk factor data, much of what is known about the natural history
      of osteoarthritis. RECENT FINDINGS: Especially given the anticipated increase in
      osteoarthritis prevalence, the need to identify risk factors for incident
      osteoarthritis, osteoarthritis progression, osteoarthritis-associated physical
      function decline, and disability is a high priority. As this review illustrates,
      the emphasis has shifted in osteoarthritis epidemiology towards the
      identification of risk factors for osteoarthritis progression rather than
      incidence. SUMMARY: Several risk factors for progression are emerging, many of
      which are impairments or pathology in the local joint organ environment. This
      shift in focus relates in part to the concept that local risk factors might
      ultimately be targeted to delay osteoarthritis progression or to enhance the
      effect of a disease-modifying drug.

PMID- 16462519
TI  - Genetic epidemiology of rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: This review aims to summarize articles published between
      October 2004 and November 2005 that have investigated the genetic epidemiology of
      rheumatoid arthritis. RECENT FINDINGS: The consistent replication of an
      association between the R620W single nucleotide polymorphism in PTPN22 and
      rheumatoid arthritis clearly establishes this polymorphism as an important risk
      factor for rheumatoid arthritis. SUMMARY: Genetic investigations of rheumatoid
      arthritis have predominantly been single nucleotide polymorphism-based candidate
      gene association studies searching for markers of susceptibility, severity or
      treatment response. Studies of the human leukocyte antigen region have refined
      and added to our understanding of the complex associations to polymorphisms with
      this locus. PTPN22 has emerged strongly as a genuine rheumatoid arthritis
      susceptibility gene with replications of the association to the R620W single
      nucleotide polymorphism. Many investigations have been conducted on the genetics
      of treatment response -- some 'generic' and others specific in terms of
      identifying genetic influences to the mode of action and metabolism of particular
      agents.

PMID- 16462521
TI  - Imaging outcomes and their role in determining outcomes in osteoarthritis and
      rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: This review describes the advances in knowledge of outcomes
      that have occurred recently as a result of imaging research in both
      osteoarthritis and rheumatoid arthritis. RECENT FINDINGS: Recent imaging advances
      in osteoarthritis have offered insights into fundamental questions including the
      cause of pain and reasons for disease progression. Although ongoing disease
      modification clinical drug trials in osteoarthritis mostly use standardized plain
      radiographs to monitor structural changes in the joint, magnetic resonance
      imaging is rapidly evolving as a method of monitoring joint structure and with
      time may become the preferred method of monitoring this feature in osteoarthritis
      clinical trials. The past decade has seen major advances in the treatment of
      rheumatoid arthritis in which imaging determines whether individual agents or
      therapeutic regimens are structure modifying. Although conventional radiography
      remains the gold standard for assessing structural progression in rheumatoid
      arthritis, growing work on the performance metrics of magnetic resonance imaging
      has resulted in its increasing use in trials. Ultrasonography shows preliminary
      promise as a useful outcome measure. SUMMARY: Recent advances in imaging are
      improving our understanding of the etiopathogenesis and treatment of persons with
      osteoarthritis and rheumatoid arthritis. Complex challenges face us over the
      coming years as clinicians and researchers grapple with the use of these new
      techniques, the insights they may provide, and their clinical application.

PMID- 16462522
TI  - Current issues in joint replacement surgery.
AB  - PURPOSE OF REVIEW: Joint replacement surgery continues to grow in sheer number of
      procedures and quantity of research. We wish to highlight the key findings in the
      literature about variations in utilization, timing of procedure, outcomes, and
      minimally invasive techniques. RECENT FINDINGS: Several studies reinforce the
      improved pain and function after joint replacement surgery. The best predictor of
      postoperative pain and function appears to be preoperative pain and function,
      respectively. In one study, authors expressed concern that patients may be
      systematically reporting better outcomes than they truly achieve. In spite of the
      generally favorable results after surgery, there remains considerable geographic,
      racial, and gender variation in utilization. The optimal timing for surgery is
      unknown but may be influenced by the advent of the newer longer-lasting
      prosthesis. Patients with poorer preoperative function tend to have poorer
      outcomes, regardless of baseline pain or function. Evidence thus far has
      demonstrated similar outcomes between minimal and standard incisions for hip
      arthroplasty. SUMMARY: Advances in our understanding of outcomes after joint
      replacement aid in predicting best candidates for surgery. More study is needed
      on the optimal timing of replacement surgery and the variations in utilization.

PMID- 16462523
TI  - New drugs for crystal deposition diseases.

PMID- 16462524
TI  - Current trends in crystal identification.
AB  - PURPOSE OF REVIEW: This review is an attempt to keep current in the sparse
      literature addressing the still underutilized area of crystal identification.
      RECENT FINDINGS: The emphasis has been on the subtleties of the microscopic
      identification of common crystals and other less common potentially confusing
      crystals. Imaging is noted to provide increasing help, but microscopic crystal
      identification remains the gold standard. SUMMARY: Quality control is still a
      concern as is the infrequency of attempted arthrocentesis for crystal
      identification.

PMID- 16462525
TI  - Determinants of pathological mineralization.
AB  - PURPOSE OF REVIEW: Physiological mineralization is necessary for the formation of
      skeletal tissues and for their appropriate functions during adulthood.
      Pathological or ectopic mineralization of soft tissues, including articular
      cartilage and cardiovascular tissues, leads to morbidity and mortality. Recent
      findings suggest that the mechanisms and factors regulating physiological
      mineralization may be identical or similar to those regulating ectopic
      mineralization. Therefore, the purpose of this review is to describe the current
      knowledge of mechanisms and determinants that regulate physiological
      mineralization and how these determinants can be used to understand ectopic
      mineralization better. RECENT FINDINGS: Recent findings have indicated that
      physiological and pathological mineralization are initiated by matrix vesicles,
      membrane-enclosed particles released from the plasma membrane of mineralization
      competent cells. An understanding of how these vesicles initiate the
      physiological mineralization process may provide novel therapeutic strategies to
      prevent ectopic mineralization. In addition, other regulators (activators and
      inhibitors) of physiological mineralization have been identified and
      characterized, and evidence indicates that the same factors also contribute to
      the regulation of ectopic mineralization. Finally, programmed cell death
      (apoptosis) may be a contributor to physiological mineralization, and if
      occurring after tissue injury may induce ectopic mineralization and
      mineralization-related differentiation events in the injured area and surrounding
      areas. SUMMARY: This review describes how the understanding of mechanisms and
      factors regulating physiological mineralization can be used to develop new
      therapeutic strategies to prevent pathological or ectopic mineralization events.

PMID- 16462526
TI  - Role of the progressive ankylosis gene in cartilage mineralization.
AB  - PURPOSE OF REVIEW: Among the myriad of players in the calcification of cartilage,
      ANK is a relatively new entrant. It is a multipass transmembrane protein that
      regulates the transport of inorganic pyrophosphate between the cell and the
      extracellular space. Mutations in ANK result in two distinct calcification
      disorders: craniometaphyseal dysplasia and familial calcium pyrophosphate
      dihydrate deposition disease. The purpose of this review is to highlight recent
      work on the role of ANK in physiological and pathological calcification of
      articular and growth plate cartilage. RECENT FINDINGS: New information on the
      function of ANK suggests that the protein is part of a constellation of critical
      components that interact to regulate the elaboration of inorganic pyrophosphate.
      In addition to ANK, these components include alkaline phosphatase, the ectoenzyme
      PC-1, and osteopontin. ANK expression is also regulated by a variety of growth
      factors and cytokines that may further affect the transport of inorganic
      pyrophosphate and may be particularly relevant to the increased levels of
      expression of ANK in cartilage from chondrocalcinosis and osteoarthritis
      patients. SUMMARY: Additional studies will be required to understand the
      contribution of ANK in shaping the fine balance of components necessary for
      crystal deposition in degenerating articular cartilage. Furthermore, the precise
      role of inherited mutations in ANK on the elaboration of inorganic pyrophosphate,
      and the ultimate deposition of either basic calcium phosphate or calcium
      pyrophosphate dihydrate crystals, remains unclear.

PMID- 16462528
TI  - Recent developments in diet and gout.
AB  - PURPOSE OF REVIEW: Gout is the most common inflammatory arthritis in men,
      affecting approximately 1-2% of adult men in Western countries. United States
      gout prevalence has approximately doubled over the past two decades. In recent
      years, key prospective epidemiological and open-labeled dietary studies, coupled
      with recent advances in molecular biology elucidating proximal tubular urate
      transport, have provided novel insights into roles of diet and alcohol in
      hyperuricemia and gout. This review focuses on recent developments and their
      implications for clinical practice, including how we advise patients on
      appropriate diets and alcoholic beverage consumption. RECENT FINDINGS: Studies
      have observed an increased risk of gout among those who consumed the highest
      quintile of meat, seafood and alcohol. Although limited by confounding variables,
      low-fat dairy products, ascorbic acid and wine consumption appeared to be
      protective for the development of gout. SUMMARY: The most effective forms of
      dietary regimen for both hyperuricemia and gout flares remains to be
      unidentified. Until confirmed by a large, controlled study, it is prudent to
      advise patients to consume meat, seafood and alcoholic beverages in moderation,
      with special attention to food portion size and content of non-complex
      carbohydrates which are essential for weight loss and improved insulin
      sensitivity.

PMID- 16462527
TI  - Basic calcium phosphate crystals: pathways to joint degeneration.
AB  - PURPOSE OF REVIEW: Basic calcium phosphate crystals have long been associated
      with rheumatic syndromes. Although an understanding of the molecular mechanisms
      involved in generating these pathological effects has been significantly advanced
      in recent years, it is still incomplete. RECENT FINDINGS: Basic calcium phosphate
      crystals have been shown to increase prostaglandin E(2) production in human
      fibroblasts, mediated by the induction of both cyclooxygenases 1 and 2. Basic
      calcium phosphate crystals have also been found to upregulate IL-1beta in
      fibroblasts and chondrocytes. The upregulation of inducible nitric oxide synthase
      and stimulation of nitric oxide production in chondrocytes by octacalcium
      phosphate crystals has been demonstrated. The involvement of protein kinase C
      isoforms in basic calcium phosphate crystal-mediated matrix metalloproteinase 1
      and 3 expression in human fibroblasts has been clarified. Two pathways are
      involved: protein kinase Calpha mediates the calcium-dependent pathway, whereas
      protein kinase Cmu activates the extracellular-regulated kinase pathway in a
      calcium-independent cascade. In addition, basic calcium phosphate crystals
      activate the transcription factor Egr-1, an effect that may contribute to the
      mitogenic effect of these crystals on fibroblasts. SUMMARY: Recent findings have
      emphasized the potential for basic calcium phosphate crystals to stimulate the
      production of a variety of inflammatory mediators such as prostaglandin E(2),
      nitric oxide, IL-1beta and matrix metalloproteinases, and have helped to
      elucidate the mechanisms of these effects. Such advances are essential for the
      ongoing search for effective therapies for basic calcium phosphate crystal
      associated diseases.

PMID- 16462529
TI  - New insights into gout epidemiology.
AB  - PURPOSE OF REVIEW: The systematic study of gout dates to antiquity, to
      Hippocrates' initial descriptions of disease risk factors including advancing
      age, female menopause, and male sex. Although urate crystal diagnosis remains the
      gold standard for diagnosis it is impractical at a population level. Beyond
      crystal diagnosis, progress in gout epidemiology has been hampered by the lack of
      a standardized approach in defining case status. RECENT FINDINGS: Substantial
      progress has been made in furthering our understanding of gout over the last few
      decades. Taken together, epidemiologic investigations suggest that gout frequency
      is on the rise worldwide. Our understanding of gout risk factors continues to
      expand with the recent availability of well designed prospective cohort studies
      from both the USA and abroad. Moreover, recent investigations have shed important
      insight on the complex relationships of hyperuricemia, gout, and comorbid
      conditions, particularly the association of serum urate levels with
      cardiovascular morbidity and mortality. SUMMARY: Despite our growing
      understanding of the many facets of this age-old condition, current evidence
      continues to underscore the frequency with which gout is characterized by
      suboptimal care. Below we review our current knowledge of gout epidemiology with
      an emphasis on the association of hyperuricemia with cardiovascular comorbidity
      and evidence and determinants of continued suboptimal care in gout.

PMID- 16462530
TI  - Current world literature.

PMID- 16462534
TI  - Improved clinical outcome with transjugular intrahepatic portosystemic stent
      shunt utilizing polytetrafluoroethylene-covered stents.
AB  - BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic stent-shunt (TIPSS)
      with standard uncovered stents has a 50% one-year primary patency rate, and is
      complicated by hepatic encephalopathy in 35% of patients. Newer covered stents
      appear to have improved patency. This large study aimed to assess the shunt
      function and clinical efficacy of polytetrafluoroethylene-covered stents in a
      single centre. METHODS: A total of 316 patients with uncovered stents before the
      introduction of covered stents (group 1) and 157 patients with the Viatorr Gore
      polytetrafluoroethylene-covered stents at the time of TIPSS creation (group 2)
      were studied. RESULTS: The mean follow-up was 22.8+/-25.4 and 13.1+/-12.5 months,
      respectively (P<0.01). Shunt insufficiency was greater in group 1 [54 versus 8%
      at 12 months; relative hazard (RH) 8.6; 95% confidence interval (CI) 4.8-15.5;
      P<0.001]. The incidence of variceal rebleeding was greater in group 1 (11 versus
      6% at 12 months; RH 2.4; 95% CI 1.1-5.1; P<0.05). The incidence of hepatic
      encephalopathy was greater in group 1 (32 versus 22% at 12 months; RH 1.5; 95% CI
      1.1-2.3; P<0.05). Mortality was similar in the two groups. CONCLUSION: The
      Viatorr type of polytetrafluoroethylene-covered stent results in vastly improved
      patency compared with uncovered stents, with reduced rates of variceal rebleeding
      and hepatic encephalopathy. This type of covered stent has the potential for
      superior clinical efficacy compared with uncovered stents.

PMID- 16462535
TI  - Prevalence of liver steatosis in patients with chronic hepatitis B: a study of
      associated factors and of relationship with fibrosis.
AB  - OBJECTIVES: The clinical significance of hepatic steatosis in chronic hepatitis B
      virus patients is poorly understood. The purpose of this study was to determine
      risk factors for liver steatosis in chronic hepatitis B patients and its
      relationship with fibrosis. METHODS: We retrospectively evaluated liver biopsies
      from patients with chronic hepatitis B treated in our department. Patients co
      infected with other viruses (hepatitis C virus, HIV) or suffering from liver
      disease of any other cause were excluded from the study, as well as patients
      consuming alcohol above 30 g/day for males or 20 g/day for females. Liver
      steatosis, necroinflammation and fibrosis were assessed. RESULTS: A total of 233
      patients with chronic hepatitis B were included in the study. The mean age was
      44.7+/-16.2 years. There were 164 men (70.4%) and 69 women (29.6%). The majority
      of patients were HbeAg-negative, 196/233 (84.1%). Thirty-seven patients had
      cirrhosis (15.9%). Steatosis was present in 42 patients (18%). Steatosis was
      independently associated with fasting glucose level (P=0.019) and being
      overweight (body mass index >or=25; P=0.021). No correlation was found with stage
      of fibrosis, grade of inflammation, alcohol use or other parameters. Ninety-four
      out of 233 patients (40.3%) had advanced fibrosis. Patients with advanced
      fibrosis were older than those with minimal or no fibrosis (47.6+/-17 versus
      42.3+/-15.2 years, P=0.024) and more frequently had a higher grade of
      necroinflammation activity (57/94 (60.6%) versus 26/139 (18.7%), P<0.0001). There
      was no significant association between advanced fibrosis and the presence of
      steatosis or mild alcohol consumption. CONCLUSION: Hepatic steatosis is present
      in 18% of our patients with biopsy-proven chronic hepatitis B. Steatosis is
      independently associated only with body mass index and fasting glucose level,
      risk factors for metabolic steatohepatitis, and was not correlated with the
      degree of fibrosis.

PMID- 16462536
TI  - Comparative analysis of expression profiling of early-stage carcinogenesis using
      nodule-in-nodule-type hepatocellular carcinoma.
AB  - BACKGROUND: Nodule-in-nodule-type hepatocellular carcinoma (NIN-HCC) is a useful
      model to illustrate the multi-step nature of hepatocarcinogenesis. To identify
      large-scale molecular change in early hepatocarcinogenesis, the expression
      profile of NIN-HCC was compared with those from three sets of individual high
      grade dysplastic nodules (HGDN) and grade 1 hepatocellular carcinomas. METHODS:
      We compared expression profiles of inner grade 1 hepatocellular carcinoma nodules
      and peripheral HGDN in one case of NIN-HCC using spotted-oligonucleotide DNA
      microarray. The relevant outlier genes assumed to associate with early
      carcinogenesis in hepatocellular carcinoma were identified by comparative
      analysis of NIN-HCC and individual cases of HGDN and grade 1 hepatocellular
      carcinoma, respectively. RESULTS: From this analysis we extracted a total of 40
      genes, consisting of 28 up-regulated genes and 12 downregulated genes, and more
      than a two-fold change in grade 1 hepatocellular carcinoma compared with HGDN.
      CONCLUSION: We assessed the expression profiles of pre-neoplastic lesions and
      grade 1 hepatocellular carcinoma using oligonucleotide microarray analysis and
      found high stringent outlier genes that are presumably directly involved in the
      transition from dysplastic nodule to the early stage of hepatocellular carcinoma
      by utilizing NIN-HCC.

PMID- 16462537
TI  - Optimizing quality of outpatient care for patients with inflammatory bowel
      disease: the importance of specialist clinics.
AB  - BACKGROUND: Most patients with inflammatory bowel disease (IBD) undergo long-term
      outpatient follow up. However, quality of care provided by specialist and non
      specialist IBD clinics is rarely critically audited. OBJECTIVE: To compare the
      standard of outpatient care provided by general gastroenterology and specialist
      IBD clinics within a single hospital using defined quality criteria. METHODS: The
      case notes of 60 consecutive patients with IBD attending general gastroenterology
      clinics and of 100 patients attending the specialist IBD clinic were reviewed for
      fulfillment of six quality criteria over the preceding 18 months. RESULTS: The
      proportion of patients fulfilling all six criteria was higher in the specialist
      IBD clinic. In the specialist IBD clinic, compared with the general
      gastroenterology clinics, blood tests were performed with appropriate frequency
      during the initiation of immunosuppressive treatment in 7/11 versus 2/12 patients
      (P=0.04) and during maintenance in 24/31 versus 6/21 patients (P=0.001); bone
      protection with oral steroids were given to 25/53 versus 4/24 patients (P=0.01);
      a screening colonoscopy at 8-10 years was performed in 25/27 versus 11/20
      patients with ulcerative colitis (P=0.004); annual serum urea and creatinine
      concentrations were measured in 82/89 versus 31/45 patients prescribed 5
      aminosalicylates (P=0.001); annual liver function tests were performed in 96/100
      versus 38/60 patients (P=0.001); and annual haematinics were measured in 37/47
      versus 18/33 patients with Crohn's disease (P=0.03). CONCLUSION: By these
      criteria, the specialist IBD clinic provided better care than the non-specialist
      general gastroenterology clinics. Even in the specialist clinic, however, the
      care of a minority of patients did not fulfil certain criteria, emphasizing the
      need for a critical audit of outpatient management of IBD.

PMID- 16462538
TI  - Clinical outcome of Crohn's disease according to the Vienna classification:
      disease location is a useful predictor of disease course.
AB  - OBJECTIVES: Crohn's disease (CD) is a complex genetic disease with multiple
      clinical patterns. Clinical classifications may help to identify subgroups of
      patients that have a distinct pattern of disease, and they are also a
      prerequisite for the conduction of genetic and therapeutic studies. The aim of
      this study was to determine the usefulness of the Vienna classification in
      patient care and clinical studies. METHODS: The clinical data of patients were
      carefully reviewed retrospectively. The behaviour and location of the disease
      were determined according to the Vienna classification and additional clinical
      characteristics including surgical data, vitamin B12 status and medication were
      also assessed. RESULTS: Data according to the Vienna classification of 292 CD
      cases were available. The mean age at diagnosis was 31.4 years. The operation
      rate was higher in patients with ileocolonic localization (P<0.05) and
      stricturing and penetrating disease behaviour (P<0.001). The incidence of vitamin
      B12 deficiency was 41.9% in cases with ileal involvement and 20.7% in cases with
      disease confined to the colon. In 187 cases (64.0%) an operation was performed
      because of CD-related complications, in a majority (126, 67.4%) this took place
      within 5 years after diagnosis. Intolerance of azathioprine occurred in 36 cases
      (22.0%). CONCLUSIONS: Ileocolonic disease localization is associated with a
      complicated course of disease. Vitamin B12 deficiency occurs frequently, also in
      patients with disease apparently confined to the colon. We propose that location
      parameters can be used for the prediction of disease course in clinical settings
      and in interventional studies.

PMID- 16462539
TI  - Capsaicin receptor (TRPV1) and non-erosive reflux disease.
AB  - BACKGROUND/AIM: Non-erosive reflux disease (NERD) is a common and heterogeneous
      disorder. We hypothesized that changes in peripheral innervation may lead to
      hyperalgesia and contribute to the development of the disorder. METHODS: Patients
      referred for evaluation of reflux symptoms with wireless pH monitoring were asked
      to provide demographic and clinical data and complete a survey related to
      severity of reflux symptoms. Endoscopies were performed to rule out macroscopic
      abnormalities of the esophageal mucosa. Biopsies obtained 2 cm above the
      gastroesophageal junction were stained for protein gene product 9.5 (PGP 9.5;
      general neuronal marker) and TRPV1 (capsaicin receptor) immunoreactivity. The
      density of immunoreactive fibers in the esophageal mucosa was determined
      morphometrically. RESULTS: A total of 39 patients without evidence of Barrett's
      metaplasia, erosive or ulcerative esophagitis were enrolled. Most patients had
      daily symptoms. The total esophageal acid exposure time was 5.6+/-0.6%, with 16
      patients (41%) having increased acid reflux. Immunoreactivity for PGP 9.5 or
      TRPV1 was detected in papillary structures as well as within the epithelium (free
      intra-epithelial endings). Total acid-exposure time, but not symptom score or
      duration correlated significantly with density of PGP 9.5 immunoreactivity and
      TRPV1 positive fibers. CONCLUSION: Even in the absence of macroscopic injury,
      esophageal acid exposure is associated with changes in mucosal innervation of the
      esophagus, thus potentially further enhancing symptoms in patients with
      gastroesophageal reflux.

PMID- 16462540
TI  - Barrett's oesophagus: an audit of surveillance over a 17-year period.
AB  - OBJECTIVE: To audit whether our patients with Barrett's oesophagus (BO) enter
      into our endoscopic surveillance programme and whether they continue with it
      after entry. We have determined the incidence of oesophageal adenocarcinoma among
      our surveyed patients. DESIGN: We retrospectively audited prospectively collected
      data from our BO surveillance programme over the years 1987-2003. SETTING: An
      inner city teaching hospital. RESULTS: During these years, 466 patients with BO
      were diagnosed (392 long segment, >or=3 cm), 29 had oesophageal adenocarcinoma at
      diagnosis, 232 [195 with intestinal metaplasia (IM) on biopsy] had at least one
      follow-up endoscopy, and 205 have not been re-endoscoped. In 27 out of 205 no IM
      was present. Of the remaining 178 out of 205 with IM, 30 were within 2 years of
      diagnosis and 148 have not been re-endoscoped for the following reasons: age
      (51), non-attendance (35), not referred back by general practitioner (30), non
      oesophageal cancer (14), severe concurrent illness (12), death (three), refused
      follow-up (two), left the area (one). The 195 patients with IM who entered
      endoscopic surveillance consisted of 108 men and 87 women (aged 62.9 years, range
      31-96), were followed for a total of 1068 patient-years (average 5.5 years), and
      had 556 endoscopies (average 2.9 per patient). Ninety-seven out of 195 patients
      remain under active endoscopic surveillance but 98 discontinued for the following
      reasons: age (31), non attendance (21), death (21 including one from oesophageal
      adenocarcinoma), refused follow up (seven), concurrent illness (six), left the
      area (four), no IM on repeat biopsies (three). Of the 195 patients with IM, four
      developed low-grade dysplasia, two high-grade dysplasia and four adenocarcinoma
      (incidence 0.37%); 178 out of 195 have been maintained on proton pump inhibitor
      (PPI) therapy. CONCLUSIONS: The majority of patients with BO either do not enter
      or do not continue in an endoscopic surveillance programme. This needs to be
      acknowledged when the workload and cost of BO surveillance programmes are
      considered. The incidence of adenocarcinoma was low compared with many published
      series, and we speculate whether this is the result of maintenance PPI therapy.

PMID- 16462541
TI  - Secretory leukocyte protease inhibitor expression in various types of gastritis:
      a specific role of Helicobacter pylori infection.
AB  - OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) represents a
      multifunctional protein of the gastrointestinal mucosa exerting antimicrobial and
      anti-inflammatory effects. SLPI expression is generally induced during
      inflammation; however, Helicobacter pylori-mediated gastritis is associated with
      significantly decreased antral SLPI levels. The aim of the study was to
      investigate whether SLPI downregulation of gastric mucosa represents a specific
      phenomenon of H. pylori infection or is generally linked to gastric inflammation.
      METHODS: SLPI expression was retrospectively analysed by immunohistochemistry in
      85 paraffin-embedded samples: H. pylori-induced (n=13), non-steroidal anti
      inflammatory drug (NSAID)-enhanced (n=18), autoimmune (n=11), lymphocytic
      gastritis (n=26) and H. pylori-negative controls (n=17). The intensity of the
      staining was semiquantitatively analysed using an immunoreactivity score.
      Statistical analysis of differences was performed using an analysis of variance
      test. RESULTS: In comparison with the control group, the SLPI expression of
      antral mucosa in H. pylori-mediated and lymphocytic gastritis was significantly
      lower (P<0.001), whereas epithelial SLPI expression was not affected in NSAID
      enhanced and autoimmune gastritis either in the antrum or corpus, respectively.
      Both the H. pylori-mediated and lymphocytic gastritis revealed a significantly
      lower expression of SLPI in infiltrating immune cells (P<0.01), whereas immune
      cells infiltrating the corpus in autoimmune gastritis showed higher SLPI levels
      than the immune cells of other groups (P<0.03). CONCLUSION: The local
      downregulation of SLPI in antral mucosa is specifically linked to H. pylori
      infection and is not a general phenomenon of gastric inflammation.

PMID- 16462542
TI  - Inter-observer variations on interpretation of capsule endoscopies.
AB  - OBJECTIVE: Capsule endoscopy is a novel investigation for diagnosing small bowel
      diseases. However, its interpretation is highly subjective and the potential
      variability may compromise its accuracy and reliability. Here we studied the
      potential inter-observer variations on the interpretation of capsule endoscopy.
      METHOD: Two residents and one specialist in gastroenterology independently
      reviewed 58 capsule endoscopy studies in the same sequential order. The gastric
      transit time, small bowel transit time, and the most significant small bowel
      lesion were independently recorded. The consensus transit time was determined by
      the joint review of the three gastroenterologists. The 'gold standard' for small
      bowel diagnoses was based on final surgical, endoscopic findings or consensus
      diagnosis. RESULTS: Clinically significant and relevant small bowel lesions were
      found in 32 (55%) cases by consensus review. The overall mean accuracy in
      determining gastric emptying time, small bowel transit time and small bowel
      lesion was 89%, 76% and 80%, respectively. There was a significant difference in
      the accuracy between the residents and specialist on small bowel transit time
      (P<0.05) and small bowel diagnosis (P<0.05). The mean kappa values on small bowel
      diagnosis among the three viewers was 0.56 (range, 0.52-0.59). Among various
      small bowel diagnoses, small bowel bleeding was more accurately identified than
      other pathology. CONCLUSIONS: Our results show that there is moderate degree of
      inter-observer discrepancies on the interpretation of capsule endoscopy. A second
      reading by an experienced viewer might improve the diagnostic accuracy of this
      investigation.

PMID- 16462543
TI  - Fatal cardiomyopathy associated with pegylated interferon/ribavirin in a patient
      with chronic hepatitis C.
AB  - We report the case of a 45-year-old man with HCV treated with pegylated
      interferon-alpha/ribavirin, in whom fatal cardiomyopathy occurred. Cardiomyopathy
      is a rare complication of high dose of standard interferon but has never been
      reported with pegylated interferon. The relationship between pegylated interferon
      alpha/ribavirin and the development of cardiomyopathy is highly probable for the
      following reasons: (1) a cardiologist consultation with specific investigations
      had been performed before treatment excluding a pre-existing cardiomyopathy; (2)
      symptoms of advanced dilated cardiomyopathy appeared immediately after the end of
      treatment; (3) other causes of cardiomyopathy have been ruled out. In all except
      one of the 21 reported cases with standard interferon, cardiomyopathy was
      reversible. In our patient, fatal cardiomyopathy occurred with a usual dose of
      pegylated interferon-alpha. Clinicians should be aware of this potential
      complication when evaluating the ratio benefit/risk of treatment in patients with
      chronic hepatitis C infection.

PMID- 16462545
TI  - Segmental mediolytic arteriopathy in a patient with intraperitoneal bleeding.
AB  - Segmental mediolytic arteriopathy (SMA) is a rare condition. It was first defined
      in 1976 and has been well described in the literature, although to date the
      aetiology of the condition is unknown. In most case reports SMA is diagnosed
      retrospectively once tissue has undergone histological examination. We present
      the first known case of SMA of the colic, mid-jejunal, common hepatic,
      intrahepatic and gastric arteries to be diagnosed at angiography after multiple
      episodes of undiagnosed intraperitoneal bleeding, and, perhaps related to this,
      one of the few reported patients with SMA involving multiple intra-abdominal
      arteries to have survived.

PMID- 16462544
TI  - Resolution of diabetes in type 2 diabetic patient treated with IFN-alpha and
      ribavirin for hepatitis C.
AB  - We report on a patient whose type 2 diabetes mellitus resolved during IFN-alpha
      therapy for hepatitis C virus (HCV). A 40-year-old man was diagnosed with type II
      diabetes in year 2000. His body mass index (BMI) was 30.8 kg/m and glycosylated
      haemoglobin (HbA1c) was 10.7%. He was treated with metformin. Later, his
      glycaemic control deteriorated despite additional dietary and lifestyle advice
      and the addition of glibenclamide. He was started on subcutaneous insulin in 2002
      with the continuation of metformin. In 2003 he was diagnosed with chronic
      hepatitis caused by HCV. In September 2003 he was started on IFN-alpha and
      ribavirin. After 24 weeks of treatment his HCV polymerase chain reaction remained
      positive and treatment was stopped as per guidelines. At the commencement of
      antiviral therapy, HbA1c was 7.7%. In April 2004 his BMI of 29.38 kg/m had
      reduced and he then stopped insulin therapy because of repeated hypoglycaemia.
      After stopping insulin his HbA1c was 4.7%. Fasting plasma glucose of 6.2 mmol/l
      and anti-glutamic acid decarboxylase antibodies were negative. Urea and
      creatinine levels were normal. Most of the earlier literature describes diabetes
      developing in the course of IFN-alpha therapy for a variety of diseases. More
      recent research has described a relationship between hepatitis C infection and
      the development of diabetes and insulin resistance. Responders to IFN-alpha
      treatment manifest an improvement in insulin sensitivity compared with non
      responders after the completion of IFN-alpha therapy. Our case shows the
      resolution of pre-existing diabetes in a patient with chronic HCV infection,
      which did not respond to IFN-alpha therapy. Whether this occurred as a direct
      result of IFN-alpha on insulin sensitivity or indirectly as a result of weight
      loss because the therapy for HCV precipitated additional lifestyle changes in the
      patient is as yet unclear.

PMID- 16462546
TI  - Gastric tuberculosis presenting as linitis plastica: a case report and review of
      the literature.
AB  - Gastric tuberculosis is rare and usually presents as an ulcerated lesion or
      gastric outlet obstruction. Rarer presentations include massive gastrointestinal
      bleed and gastric perforation. A case of gastric tuberculosis presenting as
      linitis plastica is reported here. This is the first such case report. The
      patient was a young woman who presented with non-specific abdominal pain and
      significant weight loss. The gastric mucosa appeared oedematous and hyperaemic
      and there was spontaneous oozing of blood on upper gastrointestinal endoscopy.
      Computed tomography of the abdomen revealed diffuse thickening of the gastric
      wall. The diagnosis was confirmed by the presence of caseating granulomas with
      acid fast bacilli in the endoscopic biopsy specimen. The patient showed
      significant clinical improvement on four-drug anti-tuberculous treatment.

PMID- 16462548
TI  - Evidence-based psychotherapy for schizophrenia.
AB  - Many patients with schizophrenia have psychological distress and receive some
      form of psychotherapy. Several different psychotherapeutic approaches for
      schizophrenia have been developed and studied. Of these approaches, cognitive
      behavior therapy has the strongest evidence base and has shown benefit for
      symptom reduction in outpatients with residual symptoms. In addition to cognitive
      behavior therapy, other approaches include compliance therapy, personal therapy,
      acceptance and commitment therapy, and supportive therapy. Although usually
      studied as distinct approaches, the therapies overlap with each other in their
      therapeutic elements. As psychotherapy for schizophrenia further evolves, it will
      likely be informed by other psychosocial interventions used with this clinical
      population. In particular, techniques of remediating cognitive deficits, teaching
      behavioral skills, and educating about schizophrenia may be incorporated with
      psychotherapy. Future research may also consider three different goals of
      psychotherapy with this population: to provide emotional support, to enhance
      skills for functional recovery, and to alter the underlying illness process.

PMID- 16462547
TI  - Concurrent small bowel lymphoma and mycobacterial infection: use of adenosine
      deaminase activity and polymerase chain reaction to facilitate rapid diagnosis
      and treatment.
AB  - We describe the presentation and investigation of a rare case of small bowel
      lymphoma with concurrent abdominal tuberculosis, two diseases with similar
      findings at presentation, but very different treatments. We emphasize the
      importance of considering primary peritonitis in this context, and review current
      methods of rapid diagnosis of abdominal tuberculosis, which in this instance led
      to timely appropriate treatment.

PMID- 16462549
TI  - Do baseline client characteristics predict the therapeutic alliance in the
      treatment of schizophrenia?
AB  - This study examined clinical predictors of client and therapist alliance ratings
      early in therapy, the relationship between client and therapist alliance ratings,
      and the psychometric properties of the Working Alliance Inventory in individuals
      with schizophrenia receiving manual-based treatment. Assessment of clinical
      symptoms and social functioning were conducted at baseline, and alliance ratings
      were obtained at 5 weeks. The Working Alliance Inventory had high internal
      consistency, but there were low correlations between client and therapist
      ratings. Results also indicated that social functioning and the activation and
      autistic preoccupation factors on the Positive and Negative Syndrome Scale were
      significant predictors of therapists' alliance ratings. There were no significant
      relationships between clinical predictors and clients' therapeutic alliance
      ratings. The findings indicate that client interpersonal factors are significant
      predictors of the therapist-rated alliance in the treatment of schizophrenia. Low
      correlations between clients' and therapists' ratings of the alliance should be
      examined in future research.

PMID- 16462550
TI  - Solving interpersonal problems correlates with symptom improvement in
      interpersonal psychotherapy: preliminary findings.
AB  - Interpersonal psychotherapy (IPT) research has addressed outcome more than
      mechanism. This study used the novel Interpersonal Psychotherapy Outcome Scale
      (IPOS) to test the theoretical axiom that symptomatic improvement in IPT reflects
      resolution of interpersonal problem areas. The IPOS rates change in focal
      interpersonal problem areas on a 5-point scale. Patients (N = 24) and therapists
      (N = 7) in a time-limited IPT outcome study of dysthymic disorder, and patients
      (N = 11) in an open trial for posttraumatic stress disorder, completed the IPOS
      at treatment termination. All responding dysthymic subjects (N = 24) and
      therapists (N = 21) reported interpersonal gains: dysthymic patients scored 4.39
      (SD = 0.52) out of 5, therapists 4.27 (0.53). Posttraumatic stress disordered
      patients rated 4.75 (0.34). Patient and therapist IPOS ratings correlated with
      objectively measured symptomatic improvement with full or trend statistical
      significance. Despite methodological limitations, initial testing of the IPOS
      supports the theorized link between resolving interpersonal crises and
      improvement in IPT.

PMID- 16462551
TI  - Psychotropic medication use, personality disorder and improvement in long-term
      dynamic psychotherapy.
AB  - Patients receiving long-term dynamic psychotherapy often have both depression and
      personality disorders (PDs) and take medications concurrently. Our goal was to
      determine the extent of medication use in an outpatient sample and the
      relationships of medication use and PD status to diagnostic and symptom measures.
      Fifty-three patients (25 of whom were taking medications at intake) who entered a
      long-term psychodynamic psychotherapy study for the treatment of chronic or
      recurrent depression, anxiety, and/or PDs were followed up to 7 years. PD
      patients who received combined therapy showed significant improvement in
      functioning and distress, while those receiving only psychotherapy showed
      significant improvement in depression and distress. Non-PD patients receiving
      only psychotherapy showed significant improvement in functioning. Long-term
      dynamic psychotherapy was associated with improvement in symptoms and functioning
      for the sample as a whole. PD pathology and being on medications at intake acted
      as moderator variables: PD predicted a smaller effect size in depression and
      functioning, while medications predicted a smaller effect size in depression
      only.

PMID- 16462552
TI  - Incidence of schizophrenia or other psychoses in first- and second-generation
      immigrants: a national cohort study.
AB  - The main aims of this study were to investigate whether the increased risk of
      psychotic disorders among certain immigrant groups is present in the next
      generation and whether having one parent born in Sweden has a protective effect
      on the risk of psychotic disorders among second-generation immigrants. In total,
      2,243,546 individuals were followed from January 1, 1992, until December 31,
      1999, for first hospital admission for schizophrenia or other psychoses. Cox
      regression was used to estimate hazard ratios. The highest risks of psychotic
      disorders were found among first-generation and second-generation Finns, after
      adjustment for socioeconomic status. Having one parent born in Sweden had no
      protective effect on the risk of being hospitalized for psychotic disorders among
      second-generation immigrants. The disabling symptoms of psychotic disorders call
      for increased awareness among clinicians and public health planners involved in
      the treatment and prevention of psychotic disorders, especially among certain
      immigrant groups.

PMID- 16462553
TI  - Incarceration and hospital care.
AB  - Risk for jail or prison recidivism is well documented among incarcerated
      individuals with schizophrenia. However, it is less clear that risk is also high
      for psychiatric hospital readmission after accounting for mediating influences
      such as psychopathology severity, functioning level, substance misuse, and
      demographic characteristics. Relative to counterparts without prior time in jail,
      this study therefore assessed whether formerly incarcerated individuals with
      schizophrenia were more likely to repeatedly use hospital care after controlling
      for level of functioning and symptomatology. Among 315 inpatients, former inmates
      had a greater mean number of previous hospital stays than other patients (t = 
      2.13; df = 305; p = 0.03) and were more likely to visit the emergency room or be
      rehospitalized within 3 months of discharge (chi2 = 8.83; df = 1; p = 0.003).
      They were twice as likely to be readmitted, moreover, even after accounting in
      logistic regression for age, sex, race, global functioning, psychopathology
      severity, alcohol abuse or dependence, and drug abuse or dependence (OR = .49; CI
      = .26-.95). Implications for community care are discussed, and the suggestion is
      made that jail diversion programs should be renamed and refocused as "jail and
      hospital diversion."

PMID- 16462554
TI  - Correlates of self-induced vomiting and laxative misuse in a community sample of
      women.
AB  - The correlates of self-induced vomiting and laxative misuse were examined in a
      large community sample of young adult women (N = 5255). Scores on measures of
      eating disorder psychopathology, general psychological distress, functional
      impairment, as well as the use of health services for an eating or weight problem
      were compared among participants who reported regular self-induced vomiting, but
      not laxative misuse (N = 59), and those who reported regular misuse of laxatives,
      but not vomiting (N = 39). Individuals who misused laxatives were older,
      perceived poorer physical health, and were less likely to have sought treatment
      specifically for a problem with eating than those who engaged in self-induced
      vomiting. In all other respects, the groups were similar. However, individuals
      who regularly engaged in both forms of purging (N = 8) had particularly high
      levels of eating disorder and comorbid psychopathology. The perception among
      women of normal weight that only syndromes involving the use of self-induced
      vomiting constitute an eating disorder may need to be addressed in prevention
      programs. The combination of self-induced vomiting and laxative misuse may
      indicate a particularly severe psychiatric disturbance.

PMID- 16462555
TI  - Mental illness in U.S. Presidents between 1776 and 1974: a review of biographical
      sources.
AB  - Numerous historical accounts suggest the presence of mental illness in US
      Presidents, but no systematic review has been undertaken for all holders of this
      office. We reviewed biographical sources regarding mental illness in 37 US
      Presidents from 1776 to 1974. Material was extracted by one of the authors and
      given to experienced psychiatrists for independent review of the correspondence
      of behaviors, symptoms, and medical information in source material to DSM-IV
      criteria for Axis I disorders. Levels of confidence were given for each
      diagnosis. Eighteen (49%) Presidents met criteria suggesting psychiatric
      disorder: depression (24%), anxiety (8%), bipolar disorder (8%), and alcohol
      abuse/dependence (8%) were the most common. In 10 instances (27%), a disorder was
      evident during presidential office, which in most cases probably impaired job
      performance. Mental illness in heads of state is a topic deserving further
      attention. Methodological limitations of using biography to determine
      psychopathology are discussed.

PMID- 16462556
TI  - Psychophysiological effects of human-animal interaction: theoretical issues and
      long-term interaction effects.
AB  - This paper reviews literature published on the psychophysiological effects of
      long-term human-animal interaction (i.e., pet ownership, pet adoption). A
      literature search was conducted using PsycInfo and Medline databases. Although
      the available evidence is far from being consistent, it can be concluded that, in
      some cases, long-term relationships with animals may moderate baseline
      physiological variables, particularly blood pressure. Results proved more
      coherent in studies where animals were adopted by owners as part of the
      procedure. This paper examines existing hypotheses seeking to account for these
      effects and the supporting evidence. Two major hypotheses have been suggested to
      explain the psychophysiological effects of long-term interaction, namely (1)
      stress-buffering effects of noncritical social support provided by pets; and (2)
      classical conditioning of relaxation. These mechanisms may partially account for
      the long-term health outcomes observed in a number of human-animal interaction
      studies.

PMID- 16462557
TI  - Subjective perception of cognitive deficit in psychotic patients.
AB  - The objective of this study is to evaluate the subjective perception of cognitive
      deficit and how it relates to the perception of patients' relatives. Differences
      between the subjective perception of cognitive deficits in 107 DSM-IV-diagnosed
      psychotic patients and that of their relatives or caregivers were evaluated using
      the GEOPTE Scale. Fair agreement was observed between patient and family
      perception of cognitive functions, although there were important differences on
      those items that correspond to social functioning. A high degree of correlation
      was detected between the scores on this scale and clinical global impression
      scores, as well as the physicians' global impression of cognitive impairment.
      Psychotic patients maintain insight as to their cognitive deficits, but they fail
      to conserve an awareness of their perception of social functioning.

PMID- 16462559
TI  - Traumatic wound debridement: a comparison of irrigation methods.
AB  - OBJECTIVES: To test wound debridement efficacy and soft tissue damage produced by
      high-pressure pulsatile lavage (HPPL), suction irrigation, and bulb syringe
      irrigation. DESIGN: Randomized trial in an in vitro model. SETTING: Medical
      school orthopaedic department. PATIENTS/PARTICIPANTS: No patients were used in
      this study. INTERVENTION: Beef flank steaks (100-g +/- 10-g) were divided into 8
      test groups and incised uniformly. Four test groups were contaminated with 2 g of
      rock dust and 4 were not. The specimens were then treated as follows: nothing
      (control), bulb irrigation, suction irrigation, or HPPL. MAIN OUTCOME
      MEASUREMENTS: Runoff from the irrigation was collected, filtered, lyophilized,
      and ashed to allow for quantitative determination of organic and inorganic
      material removed from the wound by each irrigation method. Digital photographs of
      the tissue samples were subjected to blinded grading on a scale of 1 to 5 to
      assess macroscopic soft tissue damage. RESULTS: Qualitatively, tissue samples
      treated with HPPL consistently received worse grades for tissue damage than
      samples in any other experimental group. Quantitative soft tissue damage analysis
      revealed that significantly more organic material was removed from samples
      treated with HPPL (141.3 +/- 58.9 mg) than those treated with bulb syringe (50.7
      +/- 28.6 mg) or suction irrigation (108.7 +/- 174.5 mg). Surprisingly,
      significantly less inorganic contaminant was removed from tissue samples treated
      with HPPL (1549.6 +/- 77.3 mg) than those treated with bulb syringe (1834.9 +/-
      39.1 mg) or suction irrigation (1827 +/- 39.4 mg). CONCLUSIONS: There has been
      some concern regarding damage produced by HPPL. According to our quantitative
      soft tissue damage data, tissue treated by HPPL was damaged significantly more
      than tissue treated with bulb syringe or suction irrigation. Our qualitative
      tissue damage grade data showed that HPPL treated test groups appeared more
      damaged than other irrigation groups. Surprisingly, HPPL removed significantly
      less inorganic contaminant than other debridement methods, and it is proposed
      that HPPL may drive some contaminants deeper into the tissue rather than removing
      them. This study seems to support the concept that suction and sharp debridement,
      as practiced by most surgeons, may remove foreign bodies well without the use of
      HPPL.

PMID- 16462558
TI  - Perceived safety in disaster workers following 9/11.
AB  - The perception of being safe, perceived safety, is an important component of
      health and the ability to work after exposure to traumatic events of all kinds.
      The relationship of perceived safety to posttraumatic stress disorder and
      depression has rarely been examined. This study examined symptoms of
      posttraumatic stress disorder, depression, and perceived safety in disaster
      workers 2 weeks after the 9/11 terrorist attacks. Perceived safety was lower in
      those with greater exposure (e.g., those who felt they were in physical danger,
      worked with dead bodies, or witnessed someone being killed or seriously injured).
      Lower perceived safety was associated with greater symptoms of intrusion and
      hyperarousal but not avoidance. Safety was negatively correlated with depression
      and peritraumatic dissociation. Lowered perceptions of safety following terrorist
      events have implications for social and work-related behaviors that can affect
      long-term health, morale, and productivity in disaster workers and other first
      responders.

PMID- 16462560
TI  - Fixation of periprosthetic femoral shaft fractures associated with cemented
      femoral stems: a biomechanical comparison of locked plating and conventional
      cable plates.
AB  - To determine which of 2 techniques for the treatment of periprosthetic femoral
      shaft fractures is of greater stiffness. DESIGN: A laboratory study using 8 pairs
      of matched, embalmed femurs. METHODS: Femurs implanted with a cemented total hip
      prosthesis had a simulated periprosthetic femur fracture created distal to the
      implant. Fractures were fixed with a plate with locked screws or a plate with
      cables (Ogden construct). Fixation stability was compared in various loading
      modalities before and after cycling. Failure in torsional loading was then
      determined. The cement mantle was tested for crack propagation that may have
      occurred secondary to locked screw insertion and loading. OUTCOME MEASUREMENTS:
      Fixation stiffness (the ratio of applied load to displacement at the fracture
      site), torsional strength, mode of failure for each system, and cement mantle
      evaluation for cracks after screw insertion. RESULTS: Locked plating was stiffer
      than the Ogden construct in pre- and post-cyclic axial loading and torsion. There
      was no difference in lateral bending stability or torsional failure loads.
      CONCLUSIONS: Locked plating constructs were stiffer than the Ogden construct in
      axial loading and torsion. Although no differences in loads to failure during
      torsion were noted, locked plating constructs exhibited catastrophic failure not
      observed with the Ogden construct.

PMID- 16462561
TI  - Does fibular plating improve alignment after intramedullary nailing of distal
      metaphyseal tibia fractures?
AB  - OBJECTIVE: Evaluate whether supplementary fibular fixation helped maintain axial
      alignment in distal metaphyseal tibia-fibula fractures treated by locked
      intramedullary nailing. DESIGN: Retrospective chart and radiographic review.
      SETTING: Three, level 1, trauma centers. PATIENTS: Distal metaphyseal tibia
      fibula fractures were separated into 2 groups based on the presence of adjunctive
      fibular plating. Group 1 consisted of fractures treated with small fragment plate
      fixation of the fibula and intramedullary (IM) nailing of the tibia, whereas
      group 2 consisted of fractures treated with IM nailing of the tibia without
      fibular fixation. OUTCOME MEASURES: Malalignment of the tibial shaft was defined
      as 1) >5 degrees of varus/valgus angulation, or 2) >10 degrees anterior/posterior
      angulation. Measures of angulation were obtained from radiographs taken
      immediately after the surgery, a second time 3 months later, and at 6-month
      follow-up. Leg length and rotational deformity were not examined. RESULTS:
      Seventy-two fractures were studied. In 25 cases, the associated fibula fracture
      was stabilized, and in 47 cases the associated fibula fracture was not
      stabilized. Cases were more likely to have the associated fibula fracture
      stabilized where the tibia fracture was very distal. In multivariate adjusted
      analysis, plating of the fibula fracture was significantly associated with
      maintenance of reduction 12 weeks or later after surgery (odds ratio = 0.03; P =
      0.036). The use of 2 medial-lateral distal locking bolts also was protective
      against loss of reduction; however, this association was not statistically
      significant (odds ratio = 0.29; P = 0.275). CONCLUSIONS: In this study, the
      proportion of fractures that lost alignment was smaller among those receiving
      stabilization of the fibula in conjunction with IM nailing compared with those
      receiving IM nailing alone. Adjunctive fibular stabilization was associated
      significantly with the ability to maintain fracture reduction beyond 12 weeks. At
      the present time, the authors recommend fibular plating whenever IM nailing is
      contemplated in the unstable distal tibia-fibular fracture.

PMID- 16462562
TI  - Complications associated with the posterolateral approach for pilon fractures.
AB  - OBJECTIVE: To review the complication rates of open reduction and internal
      fixation (ORIF) of tibial pilon fractures using the posterolateral approach.
      DESIGN: Retrospective review. SETTING: Two level I trauma centers. PATIENTS:
      Nineteen consecutive pilon fractures at an average of 13 (range, 13-45) months
      follow-up. Average age 46 (range, 21-72) years. Four of 19 were open fractures.
      INTERVENTION: Because of the high incidence of wound complications associated
      with the anterior approach for pilon fractures, patients were treated with
      initial temporary external fixation followed by delayed ORIF through the
      posterolateral approach to the distal tibia. The hypothesis was that the abundant
      soft-tissue coverage of the posterior distal tibia would decrease the rate of
      wound complications. MAIN OUTCOME MEASUREMENTS: The incidence of wound
      complications, nonunion, and early posttraumatic arthritis. This was a chart and
      radiograph retrospective review. RESULTS: The mean time to definitive treatment
      was 13 (range 2-30) days. Nine of 19 patients (47%) developed complications.
      There were 6 patients with wound problems, 2 patients with aseptic nonunions, 2
      patients with infected nonunions, 3 tibiotalar fusions, and 1 patient with a 3-mm
      step off. In total, there were 14 major complications in 9 patients. Ten of 19
      patients did not have any complication. CONCLUSIONS: The posterolateral approach
      does not eliminate the complications common to other approaches, but does offer a
      potential alternative when soft tissue concerns prevent other approaches. We do
      not recommend the posterolateral approach for the routine treatment of tibial
      pilon fractures.

PMID- 16462563
TI  - Functional treatment and early weightbearing after an ankle fracture: a
      prospective study.
AB  - OBJECTIVE: Postoperative care for ankle fractures is generally 1 of 2 regimens:
      1) functional treatment combined with early weightbearing (EWB), or 2)
      immobilization in a cast/orthosis for 6 weeks without weightbearing (6WC). The
      objective of this study was 2-fold: 1) to follow a prospective group treated with
      EWB as to long-term subjective and objective outcomes, and 2) to compare a subset
      of this group with a matched group of historic controls treated with 6WC. DESIGN:
      Prospective, clinical, cohort observation, and retrospective matched pair
      analysis. SETTING: University hospital, level 1 trauma center. PATIENTS: Forty
      three patients (20 males; mean age, 49 +/- 14 years) with operated Weber B/C
      fractures underwent EWB. For comparison, 23 patients of this group were matched
      to a same number of historic controls with respect to age, gender, body mass
      index, and fracture type. INTERVENTION: Open reduction and internal fixation
      (ORIF) using a 1/3-tubular-fibula-plate for the fibula, and malleolar screws for
      the medial malleolus fracture (in cases with a bimalleolar ankle fracture)
      followed by EWB or 6WC. MAIN OUTCOME MEASUREMENTS: Olerud and Tegner scores at
      follow-up (at least 12 months after surgery), time to full weightbearing, return
      to work, pain intensity (numerical rating scale (NRS)), and hospital stay.
      Statistical comparisons were performed by using the Mann-Whitney U test or Fisher
      exact test (P < 0.05). RESULTS: Patients with EWB were full weightbearing at 7 +/
      3 weeks and returned to work at 8 +/- 5 weeks after surgery. At follow-up (mean,
      20 +/- 11 months after surgery), all EWB patients showed good results in the
      Olerud score (90 +/- 13 points). Matched-pair analysis in 23 patients in each
      group revealed differences between EWB and 6WC groups for hospital stay (mean,
      10.8 +/- 4.7 vs. 13.6 +/- 6 days; P = 0.12), time to full weightbearing (mean,
      7.7 +/- 3.1 vs. 13.5 +/- 9.4 weeks; P = 0.01), and time until return to work
      (mean 9.2 +/- 5.5 vs. 10.8 +/- 7 weeks; P = 0.63). No differences concerning pain
      intensities were observed (EWB vs. 6WC: NRS = 1.9 vs. 1.7; P = 0.12). At follow
      up, Olerud scores were generally considered good for both groups; however, mean
      values in EWB patients were slightly higher (87 +/- 14 vs. 79 +/- 19 points; P =
      0.25). In both groups, the majority of patients reached their preinjury level of
      activity as demonstrated by Tegner scores. CONCLUSIONS: EWB patients tolerated
      earlier full weightbearing compared with 6WC patients, and there were no
      disadvantages with EWB compared with 6WC concerning hospital stay, pain
      intensities, time until return to work, and Olerud/Tegner Scores. Potential
      candidates for EWB are patients with a stable osteosynthesis of their fractured
      ankles as judged by the responsible surgeon, compliance, and high motivation.

PMID- 16462564
TI  - A randomized, controlled trial of distal radius fractures with metaphyseal
      displacement but without joint incongruity: closed reduction and casting versus
      closed reduction, spanning external fixation, and optional percutaneous K-wires.
AB  - OBJECTIVES: To compare closed reduction and casting with closed reduction and
      external fixation with optional K-wire fixation for distal radius fractures with
      metaphyseal displacement but without joint incongruity. DESIGN: Prospective
      study. SETTING: Multicenter study at 3 University teaching hospitals.
      PATIENTS/PARTICIPANTS: A total of 113 skeletally mature patients with distal
      radius fractures with metaphyseal displacement, but without joint incongruity,
      were randomized to receive 1 of 2 standardized treatment protocols. Patients were
      evaluated at 6 weeks, 6 months, 1 year, and 2 years. INTERVENTION: Closed
      reduction and casting (n = 59) or closed reduction and external fixation (n =
      54). MAIN OUTCOME MEASUREMENTS: Upper extremity function was measured using upper
      extremity MFA domain scores, overall Jebsen Taylor scores, and pinch and grip
      strength tests. Global function and pain were measured using the SF-36.
      Radiographic evaluation and range of motion were documented. RESULTS: Upper
      extremity MFA scores, Jebsen Taylor scores, SF-36 bodily pain scores, and grip
      strength improved significantly during the first year for all patients. By 2
      years, mean Jebsen Taylor scores and SF 36 bodily pain scores for patients in
      both groups were similar to scores for normal age- and gender-matched population
      controls. At all points, there was a trend for better function in the external
      fixation; however, this did not reach statistical significance. There was a trend
      for better length and palmar tilt restoration with external fixation.
      CONCLUSIONS: For distal radius fractures with metaphyseal displacement but with a
      congruous joint, there exists a trend for better functional, clinical, and
      radiographic outcomes when treated by immediate external fixation and optional K
      wire fixation.

PMID- 16462565
TI  - Modification of the Ilizarov external fixator for aseptic hypertrophic nonunion
      of the clavicle: an option for treatment.
AB  - OBJECTIVE: To assess the results of treatment of aseptic hypertrophic nonunion of
      the clavicle by external fixation using a modified Ilizarov apparatus. DESIGN:
      Prospective study. SETTING: A consecutive series of 12 patients from 2
      specialized orthopaedic institutions, treated by the 3 senior authors. PATIENTS:
      Twelve patients (5 females) with a mean age of 38.7 +/- 12.4 (range, 18-50) years
      with an aseptic hypertrophic nonunion of the clavicle were treated operatively
      during the period 1994 to 1998. Ten patients had previously been treated
      nonoperatively, whereas 2 had been treated surgically; the treatment in all had
      failed. All patients had pain with shoulder stiffness. INTERVENTION: Patients
      were treated using the Ilizarov external fixation technique. The operation was
      performed under general anesthesia and an Ilizarov external fixator was applied
      percutaneously under fluoroscopic control, without a skin incision or bone
      grafting. The patients were then monitored clinically and radiologically for 24
      to 96 (mean, 45.4) months. MAIN OUTCOME MEASUREMENTS: Radiologic evaluation and
      clinical assessment by the Constant numerical score. RESULTS: The mean Constant
      preoperative score was 30.4 +/- 9 (range, 18-44). Healing of the nonunion
      occurred in all patients treated by the Ilizarov technique. Nine patients had
      pain relief and gained unlimited range of motion, whereas 3 patients had mild
      pain during elevation of the arm. A mean period of 75.4 (range, 50-95) days was
      needed for gradual bone reduction and union. The mean Constant outcome score was
      68.8 +/- 14.7 (range, 46-85). COMPLICATIONS: 2 patients had superficial pin
      infections that cleared with local therapy and antibiotics, and 1 patient had a
      reoperation for a nonunion after a fall onto the floor. CONCLUSIONS: Ilizarov
      fixation seems to be an effective method in the treatment of aseptic hypertrophic
      clavicle nonunions, even in patients where previous surgery has failed.

PMID- 16462566
TI  - The consistency between scientific papers presented at the Orthopaedic Trauma
      Association and their subsequent full-text publication.
AB  - OBJECTIVES: To determine the consistency of conclusions/statements made in podium
      presentations at the annual meeting of the Orthopaedic Trauma Association (OTA)
      with those in subsequent full-text publications. Also, to evaluate the nature and
      consistency of study design, methods, sample sizes, results and assign a
      corresponding level of evidence. DATA SOURCES: Abstracts of the scientific
      programs of the OTA from 1994 to 1997 (N = 254) were queried by using the PubMed
      database to identify those studies resulting in a peer-reviewed, full-text
      publication. STUDY SELECTION: Of the 169 articles retrieved, 137 studies were the
      basis of our study after the exclusion criteria were applied: non-English
      language, basic science studies, anatomic dissection studies, and articles
      published in non-peer-reviewed journals. DATA EXTRACTION/SYNTHESIS: Information
      was abstracted onto a data form: first from the abstract published in the final
      meeting program, and then from the published journal article. Information was
      recorded regarding study issues, including the study design, primary objective,
      sample size, and statistical methods. We provided descriptive statistics about
      the frequency of consistent results between abstracts and full-text publications.
      The results were recorded as percentages and a 95% confidence interval was
      applied to each value. Study results were recorded for the abstract and full-text
      publication comparing results and the overall conclusion. A level of scientific
      based evidence was assigned to each full-text publication. RESULTS: The final
      conclusion of the study remained the same 93.4% of the time. The method of study
      was an observational case series 52% of the time and a statement regarding the
      rate of patient follow-up was reported 42% of the time. Of the studies published,
      18.2% consisted of a sample size smaller than the previously presented abstract.
      When the published papers had their level of evidence graded, 11% were level I,
      16% level II, 17% level III, and 56% level IV. CONCLUSIONS: Authors conclusions
      were consistent with those in full-text publications. Most studies were
      observational, less than half reported on the rate of patient follow-up. Many
      abstracts followed by publication had a smaller sample size in the published
      paper. Half of all studies were graded level IV evidence.

PMID- 16462567
TI  - Modern papineau technique with vacuum-assisted closure.
AB  - We describe a contemporary modification of the Papineau technique by implementing
      a vacuum-assisted closure (V.A.C.(R)) device in lieu of wet-to-dry dressing
      changes. The method makes use of a protocol similar to that of Papineau and
      others for the treatment of chronic osteomyelitis. This protocol includes
      aggressive excisional debridement of infected or necrotic bone, open bone
      grafting with cancellous autograft, vacuum-assisted wound closure by secondary
      intent, and eradication of chronic infection with concomitant parenteral
      antibiotics. A representative case report is included to illustrate the
      technique.

PMID- 16462568
TI  - A technique for correction of equinus contracture using a wire fixator and
      elastic tension.
AB  - Equinus contracture often is a complication of trauma, burns, or neurologic
      deficit. Many patients with contractures secondary to trauma or burns have poor
      soft tissue, which makes invasive correction a less appealing option. The
      Ilizarov external fixator has been used as a less invasive attempt to correct
      equinus contracture. We describe our "dynamic" technique and present a clinical
      patient series using a variation of the unconstrained Ilizarov technique, which
      uses elastic bands rather than threaded rods to supply the corrective force.

PMID- 16462569
TI  - Vertical axis patellar dislocation with ipsilateral femoral fracture: use of a
      closed percutaneous technique for reduction of the dislocation.
AB  - Intra-articular vertical axis dislocations are rare injuries, which mostly occur
      after blunt trauma. In this type of dislocation, the patella rotates along its
      vertical axis, bringing the articular surface to face medially or laterally. A 13
      year-old boy sustained an intra-articular lateral patellar dislocation with a 90
      degrees vertical axis medial rotation, which resulted in the articular surface
      facing laterally, the medial edge of the patella pointing posteriorly, and the
      lateral edge of the patella pointing anteriorly. As a result, the patella was
      wedged between the medial and lateral femoral condyles. He also sustained an
      ipsilateral closed distal femoral shaft fracture. Closed reduction of the
      dislocation was not successful. Subsequently an A-O reduction clamp was used
      percutaneously to reduce the patellar dislocation. The femoral fracture was then
      stabilized by internal fixation using a dynamic compression plate. Isolated
      vertical and horizontal dislocations have been previously described, but the
      presence of an ipsilateral femoral shaft fracture makes this a unique case. The
      percutaneous method used for reduction of the patella has not been previously
      described. A focused review of the literature, pathoanatomy, and methods of
      treatment of this condition are presented.

PMID- 16462570
TI  - Greenstick fracture of the scapula: a cause of scapular winging.
AB  - A case of an angulated, greenstick fracture of the scapula mimicking scapular
      winging in a skeletally immature 12-year-old boy is described. The bony deformity
      was visualized with plain radiography. CT was helpful in exclusion of a thoracic
      injury or an underlying neoplasm. Closed reduction yielded satisfactory results.
      Based on this 1 case only, we recommend consideration of closed reduction in
      children with significantly angulated greenstick fractures of the scapula without
      underlying thoracic pathology.

PMID- 16462571
TI  - Monteggia fracture dislocation in a neonate resulting from birth trauma: a case
      report.
AB  - Birth-related injuries in an uncommon location may be missed initially and may
      result in significant morbidity. We report for the first time a case of a
      Monteggia fracture dislocation in a neonate resulting from birth trauma. The
      delayed presentation at 7 days made open reduction necessary in this otherwise
      nonoperatively managed injury because of the accelerated rate of bony union in
      infants. All high-risk births, including 2nd-born twins, should be thoroughly
      screened to avoid initial misdiagnosis.

PMID- 16462573
TI  - Cisplatin: continuous versus bolus.

PMID- 16462574
TI  - 3-methylglutaconic aciduria disorders: the clinical spectrum increases.

PMID- 16462575
TI  - Effects of methylenetetrahydrofolate reductase and reduced folate carrier 1
      polymorphisms on high-dose methotrexate-induced toxicities in children with acute
      lymphoblastic leukemia or lymphoma.
AB  - The authors investigated whether high-dose methotrexate-induced toxicity differed
      according to the presence of methylenetetrahydrofolate reductase (MTHFR) or
      reduced folate carrier 1 (RFC1) genetic polymorphism. The authors studied 15
      children with acute lymphoblastic leukemia or lymphoblastic lymphoma who were
      treated using protocols that included high-dose methotrexate (3.0 g/m), for an
      overall total of 43 courses. Methotrexate-induced toxicities and the plasma
      methotrexate concentrations were evaluated retrospectively. Hematologic toxicity
      was the most frequently observed toxicity, appearing in 87% of the patients. In a
      subset of patients (47%), elevation of liver transaminase levels showed a
      repeated tendency to develop. High plasma methotrexate concentrations at 48 hours
      after the methotrexate infusion were not significantly related to methotrexate
      induced toxicities except for mucositis. A generalized estimating equation
      analysis revealed that vomiting during the high-dose methotrexate treatment was
      more pronounced in patients who had a larger number of G alleles at the RFC1
      80G>A polymorphism. No significant differences in the development of other
      toxicities or in the plasma methotrexate concentrations were observed for the
      different MTHFR 677C>T or RFC1 80G>A polymorphisms. This study suggests but does
      not prove that the RFC1 80G>A polymorphism may contribute to interindividual
      variability in responses to high-dose methotrexate.

PMID- 16462576
TI  - Myeloid dysplasia in familial 3-methylglutaconic aciduria.
AB  - A kindred is reported with four members affected with neurodegenerative disorder
      and 3-methylglutaconic aciduria. Two siblings developed thrombocytopenia
      heralding a myelodysplastic syndrome; in one patient it evolved into acute
      myeloid leukemia with monosomy 7 in the marrow. The hematologic complications
      have hitherto not been previously reported in other cases of 3-methylglutaconic
      aciduria and are thus thought to represent a new disease entity. This family adds
      additional evidence to the genetic heterogeneity of Mendelian disorders in which
      the primary mutation may have a mutator effect that could give origin to
      myelodysplastic syndrome and acute myeloid leukemia through acquired chromosomal
      changes.

PMID- 16462577
TI  - Evaluation of bone mineral density of the lumbar spine in patients with beta
      thalassemia major with dual-energy x-ray absorptiometry and quantitative computed
      tomography: a comparison study.
AB  - Osteoporosis is a common, multifactorial cause of morbidity in patients with beta
      thalassemia. The present study was performed to compare bone mineral density
      (BMD) results in the lumbar spine of thalassemic patients measured by both dual
      energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT),
      and to determine their correlations with the markers of bone turnover. BMD was
      measured in the lumbar spine of 13 regularly transfused patients with beta
      thalassemia major by both DEXA and QCT. Blood and urine samples were obtained for
      the determination of biochemical and hormonal profiles. Both T-scores and Z
      scores were higher when measured by QCT (T-score = -0.41 +/- 1.31, Z-score = 
      0.56 +/- 1.08, mean +/- SD) compared with the values given by DEXA (T-score = 
      2.57 +/- 0.88, Z-score = -2.32 +/- 1.11, P = 0.0005). In comparison to DEXA, QCT
      T-scores were more closely correlated with age (r = -0.19 vs. r = -0.70, P =
      0.0068). Strong negative correlation was found between QCT values and age (r = 
      0.67, P = 0.01). In comparison to DEXA T-scores, QCT T-scores were more closely
      correlated with osteocalcin, urine N-telopeptide cross-links of type I collagen,
      and deoxypyridinoline, but without statistical significance. DEXA T-scores were
      better correlated only with urine C-terminal telopeptides of type I collagen, but
      again without statistical significance. These results imply that the two methods
      cannot be used interchangeably in assessing BMD in thalassemic patients. However,
      which one of these two techniques more precisely determines the overall strength
      of vertebrae in patients with beta-thalassemia remains to be investigated.

PMID- 16462578
TI  - "Primary" pulmonary Langerhans cell histiocytosis in a two-year-old child: case
      report and literature review.
AB  - Langerhans cell histiocytosis (LCH) can involve multiple organs. "Primary" or
      isolated pulmonary LCH is a well-described entity in young adults but is
      exceedingly rare in children younger than 15 years of age. The authors report a
      new case in a 2-year-old girl and review other reported cases in the pediatric
      population. The patient had had respiratory symptoms since early infancy
      suggestive of hyperactive airway disease. At 2 years of age, she had severe
      pulmonary insufficiency with remarkable cystic changes noted on chest imaging
      studies. Biopsy of a pulmonary lesion confirmed the diagnosis of LCH. She had no
      other organ involvement. Pulmonary histiocytosis, though rare, should be
      considered in any child with chronic respiratory disease such as bronchial
      asthma, especially when the response to anti-asthma treatment is poor and/or
      there are cystic changes on the chest x-ray.

PMID- 16462579
TI  - Neuroblastoma in southern Brazil: an 11-year study.
AB  - The authors report on the incidence and clinical characteristics of neuroblastoma
      in southern Brazil. The aims of the study were to evaluate the age at diagnosis,
      tumor stage, MYCN status, and tumor histopathology, and to relate these factors
      to survival. All patients with neuroblastoma, 15 years old or younger (n = 125),
      admitted to the three major pediatric oncology hospitals in the state of Parana
      over a period of 11 years (between January 1990 and December 2000), were included
      in the analysis. All patients were followed for at least 5 years. In addition, a
      FISH evaluation for MYCN status was conducted in a subset of 34 tumors. Overall
      survival for tumor stages 1, 2, 3, and 4 was 100%, 72%, 59%, and 17%,
      respectively. Sixty-two percent (77/125) of all patients were older than 2 years;
      these represented 71% (57/80) of the patients with stage 4 disease. Children who
      presented with an unfavorable histopathology had a significantly worse prognosis
      (20% survival) than children with a favorable histopathology (67% survival). MYCN
      amplification was detected most commonly in stages 3 and 4 tumors (13/16). These
      data showed a delayed diagnosis of neuroblastoma in children in southern Brazil,
      and consequently survival was considerably lower in these patients.

PMID- 16462580
TI  - Assessment of cardiac function in iron-deficient children without anemia.
AB  - Iron deficiency anemia may lead to impairment of many vital functions, including
      those in the cardiovascular system. However, the effects of iron depletion on
      cardiac function in the absence of anemia are not well known. In this study the
      authors examined the effects of iron deficiency without overt anemia on cardiac
      function in 59 children. Complete blood count, serum iron, serum iron-binding
      capacity, and serum ferritin levels were measured in all children. The children
      were divided into two groups according to serum ferritin levels: an iron-depleted
      group (n = 28) and a non-iron-depleted control group (n = 31). Echocardiographic
      examinations were performed using M mode and Doppler echocardiographic methods in
      all children to assess cardiac function. No statistically significant difference
      was found between the two groups in terms of echocardiographic indices. Although
      the number of subjects in this study was small, the authors conclude that iron
      deficiency in the absence of overt anemia does not lead to important changes in
      cardiac function.

PMID- 16462581
TI  - Low incidence of ototoxicity with continuous infusion of cisplatin in the
      treatment of pediatric germ cell tumors.
AB  - Cisplatin is an important chemotherapeutic agent in the treatment of many
      pediatric malignancies, but its use is limited in part by ototoxicity. The
      authors' institution has been administering standard-dose cisplatin by continuous
      infusion rather than bolus administration in germ cell tumors. The authors
      retrospectively reviewed 39 patients with germ cell tumors requiring chemotherapy
      over the past 20 years and recorded data including demographics, cumulative
      cisplatin dose, degree of ototoxicity (by the Brock grading system), and disease
      outcome. The median age was 9.4 years and the majority of children (48.7%) had
      endodermal sinus tumor. Twenty-one children received 400 mg/m of cisplatin or
      more. One child had evidence of significant ototoxicity at last follow-up (6.64
      years after diagnosis). This patient received a total cumulative dose of 500 mg/m
      of cisplatin. Eighty-two percent of children achieved clinical remission of their
      disease. The authors conclude that continuous administration of cisplatin is
      associated with minimal ototoxicity while maintaining good tumoricidal efficacy,
      and further studies using this regimen are warranted.

PMID- 16462582
TI  - Treatment of severe disseminated juvenile systemic xanthogranuloma with multiple
      lesions in the central nervous system.
AB  - Juvenile xanthogranuloma (JXG), one of the most common forms of Langerhans
      dendritic cell proliferation in young children, usually presents as spontaneously
      regressing cutaneous lesions. JXG with systemic (extracutaneous) involvement is a
      rare histiocytic disorder in which significant morbidity and death may occur. The
      systemic type, especially combined with multiple central nervous system lesions
      in young children, has a very poor prognosis. The patient described here
      presented with disseminated disease including lungs, liver, kidneys, ribs, scalp,
      and central nervous system. The patient was treated with multiagent chemotherapy
      based on the Langerhans cell histiocytosis II treatment protocol. The regimen
      used included an additional intrathecal therapy with methotrexate and
      prednisolone to control central nervous system lesions. The patient was treated
      for 28 months and has been in remission for almost 5 years.

PMID- 16462583
TI  - bcr-abl-positive T-cell acute lymphoblastic leukemia associated with parvovirus
      B19 infection.
AB  - The authors report an unusual presentation of a Philadelphia chromosome-positive
      acute lymphoblastic leukemia with two unusual features: a bcr-abl fusion mRNA
      coding for p210 protein and a T-cell immunophenotype. The patient was a 16-year
      old boy who presented with septic shock and pancytopenia, likely precipitated by
      an acute parvovirus B19 infection. Management consisted of supportive therapy,
      followed by chemotherapy for T-cell acute lymphoblastic leukemia and stem cell
      transplantation. He died 8 months after transplant due to idiopathic pneumonia
      syndrome, but without evidence of relapsed disease.

PMID- 16462584
TI  - Low oxygen saturation by pulse oximetry may be associated with a low oxygen
      affinity hemoglobin variant, hemoglobin Titusville.
AB  - The authors describe a 10-year-old Caucasian boy who presented with abnormally
      low oxygen saturation values on pulse oximetry after a routine tonsillectomy. He
      was asymptomatic and there was no personal or family history of respiratory,
      cardiac, or hematologic disorders. Multiple initial investigations were completed
      without diagnostic yield. Eventually, hemoglobinopathy studies identified the
      presence of a low oxygen affinity hemoglobin variant, characterized as hemoglobin
      Titusville. Hemoglobinopathies remain highly prevalent worldwide, with more than
      65 low oxygen affinity hemoglobin variants identified to date. Early recognition
      of abnormal hemoglobin variants in asymptomatic patients may avoid extensive,
      unnecessary medical investigations.

PMID- 16462585
TI  - Rosai-Dorfman disease: two case reports and diagnostic role of fine-needle
      aspiration cytology.
AB  - Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy
      (SHML), is a rare and self-limiting benign disorder that most commonly involves
      the cervical lymph nodes. The authors describe two cases of SHML. Fine-needle
      aspiration of the lymphadenopathy was performed in both patients.
      Immunocytochemical and histologic features, as the evidence of emperipolesis and
      S100 protein positivity on immunostaining, were typical of SHML. Fine-needle
      aspiration cytology plays an important diagnostic role in SHML and may be
      conclusive in a typical clinical setting. The diagnosis of SHML should be
      considered in the differential diagnosis of massive, painless cervical
      lymphadenopathy. Long-term follow-up is necessary to observe the complete
      regression of the massive lymphadenopathy. However, specific therapy is available
      and should be limited to patients with compressive symptoms or extranodal
      disease.

PMID- 16462586
TI  - Hydroxyurea use in Lebanese patients with beta-thalassemia intermedia.

PMID- 16462587
TI  - "The great pretender." Langerhans cell histiocytosis.

PMID- 16462588
TI  - Temporal pattern of odor administration alters hemispheric processing in humans.
AB  - Evidence from a variety of sensory modalities has suggested that the left
      hemisphere may be 'tuned' to process more rapidly changing stimuli than the right
      and some have suggested that this difference forms the foundation of the
      functional dichotomy often drawn between the two hemispheres. Odors may be
      thought to engage these same temporally dependent processes as portions of an
      odor mixture may come to be transduced into a phasic series of neural events.
      Using brain electrical activity, we show that the temporal sequence of the odor
      alters the pattern of brain electrical activity. Estimates of the source
      localization for this activity indicate that rapidly changing odors, like sounds,
      visual and tactile stimuli, show increased activity in the left hemisphere.

PMID- 16462589
TI  - Knockdown of Stat3 in C17.2 neural stem cells facilitates the generation of
      neurons: a possibility of transplantation with a low level of oncogene.
AB  - This study investigates the role of a low level of Stat3 in the C17.2 neural stem
      cells, which are popular stem cell candidates for transplantation research. The
      results reveal that C17.2 neural stem cells will undergo increased
      differentiation into neurons without generating glia after knockdown of Stat3
      expression via an interfering RNA expression plasmid. As constitutively activated
      Stat3 is considered to be an oncogene, this study raises the possibility of stem
      cell transplantation with a low level of Stat3 to reduce the oncogenesis and
      facilitate the generation of neurons.

PMID- 16462590
TI  - Expression of chaperonin 60 in the hippocampus of the streptozotocin diabetic
      rat.
AB  - Mitochondrial dysfunction and oxidative stress are implicated in the pathological
      changes observed in the diabetic central nervous system. In this study, using the
      streptozotocin-induced diabetic rat model we document for the first time the over
      expression of a mitochondrial specific stress protein (chaperonin 60) in the
      CA1/CA3 regions of the diabetic hippocampus in the absence of neurodegeneration.
      The increase in expression of chaperonin 60 was not observed in the cohort
      treated with insulin, suggesting that the observed effect was not due to
      streptozotocin per se but due to the hyperglycaemic state induced by the diabetic
      state. The expression of chaperonin 60 was also positively correlated with a
      marker of mitochondrial oxidative stress (manganese superoxide dismutase). We
      suggest that chaperonin 60 could be an early event marker of mitochondrial
      dysfunction in the diabetic central nervous system and indeed be neuroprotective
      in the early stages of hyperglycaemic-induced oxidative stress.

PMID- 16462592
TI  - Effects of prosodic emotional intensity on activation of associative auditory
      cortex.
AB  - Functional magnetic resonance imaging was used to investigate hemodynamic
      responses to adjectives pronounced in happy and angry intonations of varying
      emotional intensity. In separate sessions, participants judged the emotional
      valence of either intonation or semantics. To disentangle effects of emotional
      prosodic intensity from confounding acoustic parameters, mean and variability of
      volume and fundamental frequency of each stimulus were included as nuisance
      variables in the statistical models. A linear dependency between hemodynamic
      responses and emotional intensity of happy and angry intonations was found in the
      bilateral superior temporal sulcus during both tasks, indicating that increases
      of hemodynamic responses in this region are elicited by both positive and
      negative prosody independent of low-level acoustic properties and task
      instructions.

PMID- 16462591
TI  - Antisocial personality and stress-induced brain activation in cocaine-dependent
      patients.
AB  - We explore the neural correlates underlying distress processing in antisocial
      personality in cocaine-dependent individuals. Twenty-seven abstinent cocaine
      dependent individuals took part in script-guided stress imagery in a functional
      magnetic resonance imaging study. Regional brain activation during stress imagery
      was compared with a baseline period, for male and female participants separately.
      Their California Psychological Inventory socialization scores were then
      correlated in region of interest analysis with corticolimbic brain regions that
      showed significant activation during stress. The effect size of activity change
      in the medial prefrontal cortex is associated with lower socialization score
      (i.e. greater sociopathy) and with the change in heart rate, but only among
      female participants. These results highlight important sex differences in the
      association between antisocial personality and distress processing in cocaine
      dependent individuals.

PMID- 16462593
TI  - Responses of neurons containing VGLUT3/nNOS-cGMP in the rVLM to cardiac
      stimulation.
AB  - Responses of glutamatergic neurons in the rostral ventrolateral medulla to
      stimulation of cardiac sympathetic afferents have not been defined. Nitric oxide
      influences neural function of glutamate. We evaluated the relationship between
      vesicular glutamate transporter 3, c-Fos and neuronal nitric oxide
      synthase/soluble guanylyl cyclase in the rostral ventrolateral medulla following
      cardiac stimulation. In anesthetized cats with barodenervation and vagotomy,
      epicardial application of bradykinin, but not its vehicle, caused pressor
      responses. More vesicular glutamate transporter 3-containing neurons colocalized
      with c-Fos or c-Fos and neuronal nitric oxide synthase in the rostral
      ventrolateral medulla in bradykinin-treated cats (n = 6; P < 0.05) than in
      control animals (n = 4). Colocalization of neuronal nitric oxide synthase,
      soluble guanylyl cyclase and c-Fos or vesicular glutamate transporter 3 was noted
      following bradykinin stimulation. Findings indicate activation of rostral
      ventrolateral medulla glutamatergic neurons by cardiac stimulation, which may be
      influenced by nitric oxide via cGMP.

PMID- 16462594
TI  - Use of engineered peripheral nerve autografts for spinal cord repair.
AB  - We developed a clinically compatible protocol for the production of engineered
      tissue for grafting into the injured spinal cord. We used autologous tissue
      derived from pre-ligated peripheral nerves, which avoids supply,
      immunocompatibility and ethical hinderances, combined with non-viral
      transfection, which is a versatile and non-immunogenic gene transfer method. In
      vitro transfection of glial cells or primary tissue from pre-ligated rat
      peripheral nerve with the neurotrophic gene brain-derived neurotrophic factor
      significantly enhanced its expression, when quantified or labelled by
      immunofluorescence. Engineered tissue expressed brain-derived neurotrophic factor
      after being grafted into the spinal cord of rats that had received spinal
      contusion injury 3 weeks before. Anatomical and functional assays of repair,
      conducted on a small cohort, showed that the treatment may promote axonal
      regeneration and improve motor performance.

PMID- 16462595
TI  - Transcranial imaging of audiogenic epileptic foci in the cortex of DBA/2J mice.
AB  - Exposure to intense sound stimuli induces audiogenic seizures in DBA/2J mice. We
      investigated cortical activities during sound stimulation using flavoprotein
      fluorescence imaging. Most DBA/2J mice had seizures during intense sound
      stimulation, with more than half surviving after seizures. Surviving mice were
      anesthetized with urethane (1.6 g/kg, intraperitoneal), and the skull was exposed
      and then covered with clear resin. More than 3 days after surgery, the mice were
      lightly anesthetized with urethane (0.8 g/kg) and cortical activities during
      intense sound stimulation were visualized. Focal responses appeared near the
      somatosensory cortex together with spike activities localized in the response
      area. These findings indicate that epileptic foci of audiogenic seizure are
      formed in the cortex of DBA/2J mice.

PMID- 16462596
TI  - One-Hertz transcranial magnetic stimulation over the frontal eye field induces
      lasting inhibition of saccade triggering.
AB  - The aim of the study was to examine the effect of low-frequency repetitive
      transcranial magnetic stimulation on saccade triggering. In five participants, a
      train of 600 pulses with a frequency of 1 Hz was applied over the right frontal
      eye field and--as control condition--over the vertex. After repetitive
      transcranial magnetic stimulation application, oculomotor performance was
      evaluated with an overlap paradigm. The results show that the repetitive
      transcranial magnetic stimulation effect was specific for frontal eye field
      stimulation. Saccade latencies were found to be increased bilaterally for several
      minutes after the stimulation, and the time course of recovery was different for
      the ipsilateral and contralateral sides. The results are discussed in the light
      of possible local and remote repetitive transcranial magnetic stimulation effects
      on the oculomotor network.

PMID- 16462597
TI  - Parafascicular nucleus projection to the extrastriatal basal ganglia in monkeys.
AB  - We have analyzed the parafascicular thalamic projection to extrastriatal
      structures of the basal ganglia using anterograde and retrograde tracing in
      monkeys. We identified (1) retrogradely labeled neurons in the parafascicular
      nucleus projecting to the anteromedial, limbic part of the external and internal
      pallidum, the substantia nigra and the subthalamic nucleus, (2) labeled terminals
      scattered in all these structures after anterograde tracer injection into the
      medial part of the parafascicular nucleus and (3) individual parafascicular
      terminals that arborized rather poorly in a large portion of each basal ganglia
      structure. Our study provides evidence that the parafascicular nucleus, and
      especially its medial part, can relay emotional and motivational information back
      to all basal ganglia components in primates.

PMID- 16462598
TI  - Cancellation of a planned movement in monkey motor cortex.
AB  - Abruptly stopping a planned movement before it has even begun can be crucial to
      retarding a premature action. In the monkey motor cortex, we report herein that
      rapid cancellation of a prepared motor act involved the brief activation of
      neurons representing a movement in the opposite direction (anti-directional
      activity). When an expected GO signal failed to occur, this opposing anti
      directional discharge appeared. It coincided in time with the cessation of the
      motor cortical activity preparing the requested arm reach. We suggest that
      functional interactions between subpopulations of neurons eliciting movements in
      opposite directions could rapidly alter population dynamics, and therefore be
      used to abruptly cancel a planned movement.

PMID- 16462599
TI  - Sigma receptor ligands protect human retinal cells against oxidative stress.
AB  - This study was undertaken to investigate the role of sigma receptors during the
      oxidative damage on human retinal pigment epithelial cells, and to assess whether
      sigma receptor ligands enhance survival and protect DNA of cells challenged by
      oxidative stress. Pretreatment with PRE-084, a sigma1 receptor agonist, resulted
      in significant increased viability in a dose-related manner. DNA damage induced
      by oxidative insult was significantly lower with PRE-084. The effects of PRE-084
      were antagonized by pretreatment with sigma1 receptor antagonists (NE-100 and
      BD1047), but interestingly were synergized by cotreatment with BD1047 that also
      presented an affinity for the sigma2 receptor. The results suggest that sigma1
      receptors play an important role against retinal damage, even though sigma2
      receptor involvement cannot be excluded.

PMID- 16462600
TI  - Mesencephalic astrocyte-derived neurotrophic factor enhances nigral gamma
      aminobutyric acid release.
AB  - Mesencephalic astrocyte-derived neurotrophic factor (MANF) - one of a new class
      of astrocyte-derived human proteins--selectively promotes the survival of
      dopamine neurons of the ventral midbrain. Using the whole-cell clamp technique,
      we looked for acute effects of MANF on gamma-aminobutyric acid type A (GABAA)
      receptor-mediated inhibitory postsynaptic currents (IPSCs) in dopamine neurons of
      the substantia nigra pars compacta of 6 to 15-day-old rats. In slices, MANF
      increased the amplitude of evoked IPSCs and decreased the paired pulse ratio. In
      mechanically dissociated cells, MANF increased the frequency of spontaneous and
      miniature IPSCs, without changing their mean amplitudes; and in enzymatically
      dissociated neurons, MANF had no effect on currents induced by exogenous GABA.
      The presynaptic enhancement of GABAergic inhibition may contribute to MANF's
      protective action on dopamine cells.

PMID- 16462601
TI  - Antipsychotic-induced alterations in D2 dopamine receptor interacting proteins
      within the cortex.
AB  - Current antipsychotic treatment involves the regulation of D2 dopamine receptor
      activity in the brain. Here, we examined the effects of chronic haloperidol and
      clozapine on cortical D2 dopamine receptors and six different dopamine receptor
      interacting proteins. Using comparative immunoblot analysis, we found that
      treatment with either haloperidol or clozapine increased D2 dopamine receptors,
      calcium activator protein for secretion, protein 4.1N, and neuronal calcium
      sensor-1 expression. Treatment with clozapine increased calmodulin and
      spinophilin expression, while treatment with haloperidol decreased expression of
      these two dopamine receptor interacting proteins. Neither antipsychotic drug was
      found to have an effect on filamin-A expression. These findings underscore a role
      for cortical D2 dopamine receptor in the mechanism of antipsychotic drug action,
      and suggest dopamine receptor interacting proteins as novel targets in
      antipsychotic drug development.

PMID- 16462602
TI  - Hypoxia-sensitive domain in the human cytosolic phospholipase A2 promoter.
AB  - Transcription from the human cytosolic phospholipase A2 gene has been observed to
      be hypoxia sensitive in endothelial cells cultured from the human cerebral
      microvasculature. DNA sequence analysis of the cytosolic phospholipase A2
      promoter revealed the presence of a distal cluster of potential hypoxia-inducible
      factor-1-DNA binding sites homologous to 5'-NCGTG-3', located between -1087 and 
      996 bp of the major start of transcription at +1 bp (Genbank U08374). Gel shift
      assay showed strong hypoxia-inducible factor-1-DNA binding to only a single site
      within this cluster, and promoter deletion analysis indicated the functional
      importance of this chromatin domain in conveying oxygen sensitivity to cytosolic
      phospholipase A2 gene transcription. Non-functional hypoxia inducible factor-1
      DNA binding sites flanking a single functional hypoxia-inducible factor-1-DNA
      binding site in this hypoxia-sensitive domain may promote oxygen sensitivity via
      transcription factor clustering or Circe effects.

PMID- 16462603
TI  - Impairment of axotomy-induced pituitary adenylyl cyclase-activating peptide gene
      expression in T helper 2 lymphocyte-deficient mice.
AB  - CD4+ (T helper) lymphocytes appear to play important roles in neuron survival and
      regeneration after injury, although their functions in regulating gene expression
      in injured neurons are unknown. Mice with targeted mutations in the STAT4 and
      STAT6 genes are deficient in T helper (Th)1 and Th2 responses, respectively, and
      have been used to determine the relative importance of T helper subsets in a
      variety of inflammatory processes. As pituitary adenylyl cyclase-activating
      peptide mRNA is normally strongly induced in facial motor neurons after axotomy,
      we examined this induction in Th1 and Th2 lymphocyte-deficient and control Balb/C
      wild-type mice. As previously reported, pituitary adenylyl cyclase-activating
      peptide gene expression was strongly induced in ipsilateral but not contralateral
      motor neurons in the facial motor nucleus of wild-type mice. The mean number of
      hybridizing motor neurons in STAT4-deficient mice did not differ from that in
      wild-type mice, whereas the number in STAT6 mice was reduced by more than 50%.
      The results indicate that STAT6 plays a key role in the upregulation of pituitary
      adenylyl cyclase-activating peptide gene expression in facial motor neurons after
      injury, possibly through its role in regulating T helper cell differentiation to
      the type 2 phenotype.

PMID- 16462604
TI  - Tunicamycin decreases the probability of single-channel openings for N-methyl-D
      aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      receptors.
AB  - In whole-cell patches from cultured rat hippocampal neurons, tunicamycin (0.1-30
      microM), an inhibitor of protein N-glycosylation, depressed currents through N
      methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      receptor channels in a concentration-dependent manner. Tunicamycin shifted the
      agonist concentration-response curve for each receptor type to the right. In an
      outside-out patch-clamp configuration, tunicamycin reduced the number of single
      channel opening events in parallel with prolonged mean shut time, without
      affecting the slope conductance for both the receptors. These tunicamycin effects
      were obtained with acute treatment, suggesting an action independent of any
      blockage of N-glycosylation. Tunicamycin, thus, may modify the agonist binding
      affinity of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid receptors, thereby causing a decrease in the probability of single
      channel openings leading to the depression of whole-cell membrane currents.

PMID- 16462605
TI  - Fluoxetine reverses stress-induced fimbria-prefrontal long-term potentiation
      facilitation.
AB  - Stress has been reported to disrupt the induction of synaptic plasticity in
      different fimbria target structures. The aim of the present study was to
      investigate whether chronic mild stress may also affect synaptic plasticity in
      the medial prefrontal cortex, a fimbria target structure. Fimbria tetanus (100
      Hz) did not produce any changes in medial prefrontal cortex synaptic efficacy in
      non-stressed rats. Rats exposed to chronic mild stress, however, developed
      significant long-term potentiation. Treatment with fluoxetine (10 mg/kg,
      intraperitoneal) suppressed long-term potentiation induction in the chronic mild
      stress group. These data demonstrate that stress not only inhibits long-term
      potentiation development, as often demonstrated, but can also facilitate long
      term potentiation development in certain brain circuits.

PMID- 16462606
TI  - Selection of currently relevant words: an auditory verbal memory study using
      positron emission tomography.
AB  - Clinical and imaging studies have shown that the posterior and anterior parts of
      the limbic system make distinct contributions to memory processing. Whereas the
      medial temporal lobes and connected structures are important for learning and
      recognition of new information, the posterior orbitofrontal cortex appears to be
      crucial for the selection of currently relevant memories, that is, the ability to
      distinguish between memories that pertain to ongoing reality and memories that do
      not. Previous studies demonstrating this dissociation used repeated continuous
      recognition tasks with visual stimuli. In this H2O positron emission tomography
      study, we demonstrate that this same organizing principle also applies to
      auditory verbal information, that is, to the processing of auditorily presented
      words.

PMID- 16462607
TI  - Affective context-induced modulation of the error-related negativity.
AB  - The error-related negativity putatively reflects the activity of performance
      monitoring processes influenced by motivational factors, and is overactive in
      certain anxiety states, suggesting that affective factors affect its generation.
      We examined the effects of emotionally arousing and neutral task-irrelevant
      backgrounds on the error-related negativity to determine whether an affective
      context 'mismatch' alters error-related neural processing. Event-related
      potentials were acquired while healthy participants performed a modified Eriksen
      flanker task wherein flanker stimuli were superimposed on neutral, pleasant, and
      unpleasant pictures. The error-related negativity varied as a function of picture
      valence, peaking both earlier and larger in the context of pleasant backgrounds
      than neutral or unpleasant backgrounds. Findings support the hypothesis that
      affective factors influence the error-related negativity, potentially reflecting
      an affective mismatch associated with performance monitoring.

PMID- 16462608
TI  - Dorsal stream associations with orthographic and phonological processing.
AB  - Several studies have indicated a key role for dorsal stream processing in lexical
      decoding. To examine this relationship further, performance on orthographic and
      phonological reading tests was compared with both steady-state visual evoked
      potentials and a putative behavioral measure of dorsal stream processing,
      coherent motion detection. Frequency analysis of the visual evoked potential data
      showed power at the second harmonic to be largely confined to dorsal stream
      regions, and significantly correlated with motion detection thresholds.
      Regression analyses showed that orthographic processing was significantly
      associated with the second harmonic power. Although consistent with previous
      reports, there remains a question as to why the orthographic visual evoked
      potential power relationship did not extend to include the coherent motion
      detection measures.

PMID- 16462609
TI  - A role for the prefrontal cortex in recall of recent and remote memories.
AB  - Declarative memories are thought to be initially stored in the hippocampus, and
      then transferred to the neocortex. This is a key feature of the standard model of
      consolidation and is supported by studies reporting a requirement for activity
      within the neocortex for recall of remote, but not recent, hippocampal-dependent
      memories. New evidence from our and other laboratories, however, suggests that,
      for trace fear conditioning, memories are stored in the rodent medial prefrontal
      cortex and in the hippocampus from the time of training. Consistent with this, we
      show that activity in the medial prefrontal cortex is necessary for retrieval of
      recent and remote memories, suggesting that information stored in this
      neocortical structure from the time of training is necessary for memory recall.

PMID- 16462611
TI  - Advances in prevention of cervical cancer and other human papillomavirus-related
      diseases.

PMID- 16462615
TI  - A modification of the Mayfield horseshoe headrest allowing pin fixation and
      cranial immobilization in infants and young children.
AB  - OBJECTIVE: Pin fixation and rigid immobilization of the head is desirable in many
      neurosurgical procedures. However, these techniques are associated with
      complications in infants and young children. A simple modification of a commonly
      used cranial fixation system allows rigid, safe immobilization of the head in
      infants and children. INSTRUMENTATION: A standard Mayfield horseshoe headrest and
      cranial fixation system was adapted to allow simultaneous use of the headrest and
      three-point pin fixation. The system is compatible with most neuronavigational
      systems. RESULTS: The combined horseshoe and pin system was used successfully in
      more than 30 patients ranging in age from 6 months to 14 years. No complications
      were encountered. CONCLUSIONS: Rigid immobilization is achievable in the
      pediatric population, facilitating intracranial and frameless stereotaxy
      procedures.

PMID- 16462616
TI  - Endoscopic harvesting of the sural nerve graft: technical note.
AB  - OBJECTIVE AND IMPORTANCE: The sural nerve is the donor nerve most commonly used
      for peripheral nerve reconstruction. The objective of this paper is to present an
      endoscopic technique for harvesting these sural nerve grafts, using the Guidant
      VasoView Uniport Plus device (Guidant Corp., Indianapolis, IN), originally
      designed to obtain the saphenous vein. The importance of this technique is its
      use of a small, 12-mm incision for removing the entire sural nerve, which is an
      improvement over the two, three, or one 3-cm incisions(s) for sural nerve
      harvesting described in other publications. Endoscopic techniques, in general,
      replace the former open technique requiring a longitudinal incision along the
      entire posterior lower leg, which is a distinct advantage. CLINICAL PRESENTATION:
      Two cases of patients with lesions requiring sural nerve grafts are presented.
      Nerve action potential recordings showed no transmission in each case and nerve
      grafts were required for repair of these lesions after their resection to healthy
      appearing tissue. INTERVENTION: The first patient had a stretch contusion injury
      extending from the right C5 and C6 roots to the upper trunk (UT) and UT outflow
      to the suprascapular nerve (SSN). This patient required a sural nerve graft 20 cm
      in length, which was harvested by the described endoscopic technique within 20
      minutes. The second patient had in continuity lesions involving the C5 and C6
      roots to the UT including the SSN and the C7-middle trunk to posterior spinal
      cord. These lesions required a 31-cm sural nerve graft harvested via the
      endoscopic technique in 25 minutes. CONCLUSION: When compared with the open
      techniques, the endoscopic method using the Guidant VasoView Uniport Plus device
      has the advantages of being fast, less traumatic, safer, and resulting in a more
      aesthetic technique.

PMID- 16462617
TI  - Salvage technique of posterior iliac bolt placement in long-segment spinal
      constructs with a previous posterior iliac crest harvest: technical note.
AB  - OBJECTIVE AND IMPORTANCE: Fusion between the lumbar spine and sacrum has been
      used to treat deformity, degenerative disease, trauma, and tumor. These
      constructs have a higher failure rate when a long construct is designed, in
      patients with poor bone quality, and in patients with previous irradiation or
      with significant osteoporosis. CLINICAL PRESENTATION: Extending the construct to
      the pelvis has been shown to increase the fusion rate of these patients and to
      reduce the risk of hardware failure before fusion has occurred. INTERVENTION: We
      extend the constructs with the use of iliac bolts placed within the posterior
      iliac crests. Placement of these bolts can be challenging after the posterior
      iliac crest has been harvested for autologous bone in a previous operation.
      CONCLUSION: The purpose of this technical note is to describe our salvage
      technique of iliac bolt placement as an adjunct to lumbar-sacral fusions in a
      previously harvested iliac crest.

PMID- 16462618
TI  - Use of a tubular retractor system as a minimally invasive technique for epidural
      plate electrode placement under local anesthesia for spinal cord stimulation:
      technical note.
AB  - OBJECTIVE: To improve the technique of placement of large plate electrodes for
      spinal cord stimulation with a minimally invasive approach using the METRx
      tubular retractor system (Medtronic Sofamor Danek, Minneapolis, MN). This
      dilating system splits the paravertebral musculature, avoiding the need to strip
      these muscles from the spine. The technique described makes it possible to
      perform the procedure (currently, it is most frequently performed using general
      anesthesia) with local anesthesia and sedation, allowing test stimulation, and
      with little intraoperative or postoperative discomfort for the patient. METHODS:
      The tubular retractor system was used to approach the spine at the desired level
      using local anesthesia. A small laminectomy was performed through the working
      tube, and the plate electrodes were introduced by the same approach. Test
      stimulation could be performed to determine the correct electrode position
      because only local anesthesia was used. RESULTS: Seven patients were scheduled
      for placement of large plate electrodes for spinal cord stimulation. In six
      patients, with different indications for the placement of spinal cord
      stimulation, the electrode could be placed using the minimally invasive tubular
      retractor system approach with local anesthesia and slight sedation. A good test
      stimulation was obtained in all of the patients, resulting in good pain relief
      after definitive implantation. We were not able to perform the procedure in one
      patient because we could not reach the spinal canal at the level operated on
      previously. All patients experienced only acceptable postoperative back pain.
      CONCLUSION: Using a tubular retractor system, implantation of plate electrodes
      for spinal cord stimulation can be performed under local anesthesia with
      acceptable discomfort for the patient, making the approach of the spinal canal
      minimally invasive. This method allows test stimulation to assess the correct
      electrode position and results in less local postoperative discomfort because of
      the small-muscle splitting approach.

PMID- 16462619
TI  - Cranioplasty after trephination using a novel biodegradable burr hole cover:
      technical case report.
AB  - OBJECTIVE AND IMPORTANCE: We have developed novel biodegradable polymer implants
      by using the rapid prototyping technology fused deposition modeling. Early
      results of a clinical pilot study for cranioplasty are presented. CLINICAL
      PRESENTATION: Five patients with the diagnosis of chronic subdural hematoma were
      included in the study. After trephination and evacuation of the subdural
      hematoma, burr holes (diameter, 14 mm) were closed using a biodegradable implant
      made of polycaprolactone. Implants were computer designed with an upper rim
      diameter of 16 mm and a 14 mm body diameter with a fully interconnected,
      honeycomb-like architecture of 400 to 600 microm in pore size. INTERVENTION:
      Postoperative computed tomographic scans indicated that the plugs were stably
      anchored in the osseous host environment with no fluid collection detectable. The
      postoperative course was uneventful, and patients were discharged after 5 days.
      Follow-up scans after 3, 6, and 12 months showed that the implants were well
      integrated in the surrounding calvarial bone with new bone filling the porous
      space. CONCLUSION: These novel polymer scaffolds made of the slow-degrading
      material polycaprolactone represent a suitable implant for closure of post
      trephination defects.

PMID- 16462620
TI  - Pontine cavernous angioma resected using the subtemporal, anterior transpetrosal
      approach determined using three-dimensional anisotropy contrast imaging:
      technical case report.
AB  - OBJECTIVE AND IMPORTANCE: We describe a case of brainstem cavernous angioma
      resected by the subtemporal, anterior transpetrosal approach, selected on the
      basis of three-dimensional anisotropy contrast (3-DAC) imaging. CLINICAL
      PRESENTATION: A 64-year-old woman presented with sudden headache and gait
      disturbance. Anatomic magnetic resonance imaging showed a mass lesion in the left
      anterolateral part of the pons. On 3-DAC imaging, posteromedial compression of
      the left corticospinal and corticopontine tracts by the mass lesion was
      demonstrated. INTERVENTION: The lesion was resected through the anterolateral
      side of the pons via the subtemporal, anterior transpetrosal approach.
      Neurological symptoms improved postoperatively, and postoperative 3-DAC imaging
      demonstrated preservation of the corticospinal and corticopontine tracts.
      CONCLUSION: The technique of 3-DAC imaging may provide important information
      regarding neural tracts for the planning of brainstem surgery.

PMID- 16462621
TI  - Fusion of three-dimensional calcium rendering with rotational angiography to
      guide the treatment of a giant intracranial aneurysm: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Although three-dimensional (3D) rotational angiography
      enables the visualization of intracranial vascular anatomy with high spatial
      resolution, its ability to resolve calcified features is limited. We present a
      case in which a 3D calcium density rendering was fused with rotational cerebral
      angiography to guide the treatment strategy of a giant, calcified, partially
      thrombosed, middle cerebral artery bifurcation aneurysm. CLINICAL PRESENTATION:
      On screening magnetic resonance imaging, a 57-year-old woman with familial
      subarachnoid hemorrhage was found to harbor a giant trilobed, partially
      thrombosed, calcified aneurysm. Three-dimensional (3D) cerebral angiography
      revealed only partial contrast filling of one lobe with a daughter component.
      TECHNIQUE: A distinct rotational acquisition volume with parameters optimized for
      calcium density visualization was acquired just before the conventional contrast
      acquisition. The resulting 3D calcium volume rendering was fused with the
      vascular model. Multiplanar interactive visualization of the combined model
      uncovered heavy calcification at the neck of the aneurysm that precluded direct
      clipping, and the patient underwent endovascular coil embolization. CONCLUSION:
      Preoperative assessment of intracranial aneurysms can be facilitated by the
      current technique, which enables the detection of calcified tissue near the neck,
      which would otherwise not be possible with 3D rotational cerebral angiography
      alone.

PMID- 16462622
TI  - "Cross-over" technique for horizontal stenting of an internal carotid bifurcation
      aneurysm using a new self-expandable stent: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: To describe the use of a newly available self
      expandable stent in a cross-over approach for treatment of a large, wide-necked
      carotid termination aneurysm. CLINICAL PRESENTATION: A 58-year-old hypertensive
      woman presenting with mild headaches underwent computed tomography, which showed
      a nonruptured aneurysm of the left internal carotid artery. She subsequently
      underwent cerebral angiography, confirming that the aneurysm was located at the
      left terminal carotid segment with a wide neck. INTERVENTION: Using a cross-over
      approach from the contralateral internal carotid artery, a new self-expandable
      stent was advanced through the anterior communicating artery and placed
      horizontally across the aneurysm neck. Aneurysm occlusion was performed by
      subsequent trans-stent catheterization of the aneurysm and coil packing.
      CONCLUSION: Successful stent placement allowed subtotal coil occlusion of the
      aneurysm with a good anatomic and clinical result. No complications were
      encountered. The new self-expandable stent is a highly flexible, low-profile
      device that can be safely navigated through tortuous intracranial vessels even in
      a crossover technique. Its radial force and closed cell design is suitable for
      stent-assisted coiling and may be superior to stents with an open cell design.

PMID- 16462623
TI  - Intraorbital arteriovenous fistulae of the ophthalmic veins treated by
      transvenous endovascular occlusion: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Intraorbital arteriovenous fistulas (AVF) of the
      ophthalmic veins are an extremely rare phenomenon. This article describes two
      such cases treated solely by transvenous occlusion and not hitherto described in
      the literature. METHODS AND RESULTS: Two women, aged 51 and 63 years old,
      presented with proptosis and chemosis mimicking a carotid-cavernous fistula. In
      both cases, cerebral angiography revealed an intraorbital dural AVF of the
      superior and inferior ophthalmic vein, respectively. Both patients underwent
      transvenous ablation of the dural AVF retrograde via the facial vein and
      subsequently had complete resolution of the presenting symptoms. CONCLUSION:
      Ophthalmic vein fistulas are a rare form of AVF with presenting symptoms
      mimicking those of carotid cavernous fistulae. This report describes two cases of
      ophthalmic vein fistulas successfully treated and angiographically obliterated
      via transvenous embolization with resolution of the patient's presenting
      symptoms.

PMID- 16462626
TI  - [Assessment of the notion of remission in schizophrenia].

PMID- 16462625
TI  - [New perspectives in the management of psychosis].

PMID- 16462627
TI  - [What are the representations of remission for the psychiatrist?].

PMID- 16462628
TI  - [What are the representations of remission for the patient?].

PMID- 16462630
TI  - [Criteria of remission in schizophrenia].

PMID- 16462631
TI  - [Cognitive functions and remission].

PMID- 16462633
TI  - [Treatment of major depressive disorder. Is one really cured?].

PMID- 16462632
TI  - [Daily life of schizophrenic patients "in remission"].

PMID- 16462635
TI  - [Treatment of major depressive disorder. Criteria for considering the patient
      cured after an episode of major depression].

PMID- 16462637
TI  - [Treatment of major depressive disorder. The place of residual symptoms: between
      remission and cure].

PMID- 16462639
TI  - [Treatment of major depressive disorder. Prognostic criteria of a patient cured].

PMID- 16462641
TI  - [Treatment of major depressive disorder. The weight of life events in unipolar
      and bipolar disorders].

PMID- 16462643
TI  - [Treatment of major depressive disorder. Cure and pathological personalities].

PMID- 16462647
TI  - [Treatment of major depressive disorder. The risk of chronicisation].

PMID- 16462645
TI  - [Treatment of major depressive disorder. Comorbidity, depression and anxiety:
      dangerous liaisons].

PMID- 16462649
TI  - [Treatment of major depressive disorder. Criteria for choosing an
      antidepressant].

PMID- 16462650
TI  - [Treatment of major depressive disorder. What is the risk/benefit ratio of long
      term antidepressors?].

PMID- 16462651
TI  - [Treatment of major depressive disorder. How to manage depression in the long
      term without resorting to drugs].

PMID- 16462653
TI  - [La Presse Medicale: a step forward].

PMID- 16462652
TI  - [Treatment of major depressive disorder. Interpersonal therapies].

PMID- 16462654
TI  - [The new face of reconstructive surgery].

PMID- 16462655
TI  - [Chronic kidney disease, too often, too late].

PMID- 16462656
TI  - [Gastroesophageal reflux: epidemic correlated with obesity?].

PMID- 16462657
TI  - [Medical files: a new partnership in health care].

PMID- 16462658
TI  - [Variant Creutzfeldt-Jakob disease, 10 years later].

PMID- 16462659
TI  - [Continued late referral of patients with chronic kidney disease. Causes,
      consequences, and approaches to improvement].
AB  - OBJECTIVES: Efforts in recent years have aimed at increasing physicians'
      awareness of the frequent and harmful consequences of late referral to
      nephrologists of patients with chronic kidney disease (CKD), shown in repeated
      concordant studies. We sought to determine whether these efforts have led to
      improved predialysis care of these patients. METHODS: This study included all
      1391 consecutive patients who began maintenance dialysis at Necker Hospital
      between January 1989 and December 2000. We examined baseline data and outcomes
      and determined for four three-year periods the percentage of patients who
      received early specialized care (at least 6 months before onset of dialysis).
      RESULTS: Late referral (<6 months before dialysis) did not change significantly
      over the four periods, remaining around 30%, even during the most recent period
      (1998-2000). Clinical condition and laboratory indicators of patients referred
      early but not those referred late improved in the latest period, compared with
      the initial period (1989-1991). Overall, prevalence of major cardiovascular
      events (myocardial or cerebral infarction, peripheral arteriopathy, or heart
      failure) was more than twice as high in patients who received nephrologic care
      for less than 6 months and nearly twice as high even in those followed 6-35
      months than in patients followed for at least 36 months before beginning
      dialysis. Subsequent mortality after maintenance dialysis was also significantly
      higher in patients with late referral than in those followed at least 3 years
      before dialysis. Multivariate Cox proportional model analysis identified graded
      duration of predialysis nephrologic care as a significant independent factor
      predictive of risk of mortality while on dialysis. CONCLUSION: Late referral of
      CKD patients for specialist care remains frequent, around 30%, although it is
      most often unjustified. Late referral deprives the patient of early
      implementation of a reno- and cardioprotective therapeutic strategy that reduces
      cardiovascular comorbidity and mortality. Better coordinated cooperation between
      family doctors and nephrologists, through the implementation of regional
      healthcare networks, now appears as the most effective way to improve the care of
      CKD patients.

PMID- 16462660
TI  - [Gastroesophageal reflux in the French general population: national survey of
      8000 adults].
AB  - OBJECTIVES: To assess the population-based prevalence in France of
      gastroesophageal reflux disease (GERD) and to report its characteristics,
      consultation rate, modes of management, as well as patients' satisfaction.
      METHODS: This epidemiological quantitative mail survey sent to a sample of 8000
      persons representative of the French adult population comprised 46 questions
      about GERD, its risk factors, management, last episode, and satisfaction with
      treatment. GERD was defined in accordance with the guidelines of the 1999
      consensus conference as the existence of typical symptoms (heartburn, acid
      regurgitation) and frequent GERD as occurring at a frequency of at least once a
      week. RESULTS: The overall prevalence of GERD in France is 31.3%. The prevalence
      of frequent GERD is 7.8% (6% among those younger than 50 years, 10% among those
      older than 50). Most subjects with frequent GERD (86%) had seen a doctor for it,
      often long after the first occurrence of symptoms - 26% had waited for more than
      one year before consulting - while 14% had never discussed it with a doctor,
      mainly because they considered it not serious and treated it themselves. Of those
      who had consulted, 58% had undergone an endoscopy. Most subjects (85%) had
      treated their last episode of frequent GORD, most often by their doctor's
      prescription treatment (68%), less often by self-treatment or a medication
      recommended by the pharmacist or both (17%). The prescription treatment was most
      often used alone (61%) and only rarely combined with self-treatment or a
      pharmacist's recommendation (7%). Two thirds of the subjects had used a single
      medication, and one-third a combination of drugs. Single medications were mainly
      proton-pump inhibitors (PPIs) (45%) and antacids/alginates (46%). Combinations
      were essentially made up of PPIs (83%), most often combined with
      antacids/alginates (61%). Two-thirds of subjects reported that they were entirely
      satisfied with their treatment, but symptoms had persisted in 24% of treated
      subjects. DISCUSSION: Prevalence of frequent GERD increases with age. Sex,
      obesity, and consumption of tobacco and alcoholic beverages do not appear to
      affect it markedly. The proportion of subjects with frequent GERD with no regular
      medical follow-up and resorting to self-treatment is substantial. Only two thirds
      are totally satisfied with their treatment. CONCLUSION: Nearly 3.5 million French
      adult subjects currently suffer from frequent GERD, and many do not - or wait
      unduly to - see a doctor, despite symptom frequency. Better management of
      frequent GERD in France remains desirable in order to improve symptom relief and
      surveillance of possible complications.

PMID- 16462661
TI  - [Treatment of acute maxillary sinusitis in adults. Comparison of cefpodoxime
      proxetil and amoxicillin-clavulanic acid].
AB  - OBJECTIVE: The aim was to demonstrate the equivalence of the clinical efficacy
      and safety of cefpodoxime-proxetil (200 mg bid for 5 days) to that of amoxicillin
      clavulanic acid (1 g/125 mg bid for 8 days) in adults with acute maxillary
      sinusitis. METHOD: In this prospective, multicenter, centrally-randomized, open
      label study, 73 general practitioners and 11 ear, nose, and throat specialists
      included 512 patients with unilateral acute maxillary sinusitis. RESULTS: The
      clinical success rates at day 12-19 in the per-protocol population (primary
      analysis) were 92.3% (215/233) in the cefpodoxime-proxetil group and 93.6%
      (204/218) in the amoxicillin-clavulanic acid group. The 95% confidence interval
      of [6.5%; 3.9%] demonstrated that cefpodoxime-proxetil was not inferior to
      amoxicillin-clavulanic acid. Cure rates at follow-up (day 25-30) were 90.6% and
      92.7%, respectively. Results were similar in the intent-to-treat population.
      Compliance was significantly better in the cefpodoxime-proxetil group (99.2%
      versus 95.5%; p=0.011). Tolerance was also significantly better: 1.2% (3/247) of
      cefpodoxime-proxetil patients reported a treatment-related adverse event,
      compared with 10.7% (26/244) in the amoxicillin-clavulanic acid group (p<0.001).
      Most events were gastrointestinal and of mild to moderate intensity. CONCLUSION:
      In this study, a 5-day course of cefpodoxime-proxetil at 200 mg bid was as
      clinically effective as amoxicillin-clavulanic acid 1 g/125 mg bid for 8 days
      with a significantly better safety profile and compliance.

PMID- 16462662
TI  - [Providing medical files to patients: analysis of 52 requests].
AB  - BACKGROUND: Since enactment of a statute on 4 March 2002 to allow patients direct
      access to their medical files, the number of requests for these files has
      increased substantially. The objective of this survey was to learn the patients'
      motivations for requesting files, what they did with them once they received
      them, and the effects of this direct access on the patient and on the
      relationship and confidentiality between physician and patient. METHODS: A
      questionnaire was sent to 100 persons randomly selected among patients requesting
      their medical file from the Dijon University Hospital Center after the new law
      became effective. RESULTS: The response rate to this survey was 58%. In 75% of
      the cases, patients requested their own medical files. Their reasons varied:
      curiosity (38%), transfer of the file to another physician (35%), disagreement
      with the medical team (12%), death of a family member (10%). After receiving the
      file, 35% of the respondents read it with a physician and 13% with their
      attorney. In two thirds of the cases, the medical files were transmitted directly
      to a third party: physician (51%), attorney (34%), or insurance company (20%).
      The file provided patients with the information they wanted in 79% of cases and
      allowed them to sue the physician in 12%. Only a quarter of the persons
      requesting files met with the physician concerned before making their request.
      CONCLUSION: The disclosure of secret medical information can lead to serious
      consequences to patients, of which they are not necessarily aware. This may
      require that clear information about patient-doctor confidentiality be provided
      to persons requesting files.

PMID- 16462663
TI  - Assessment of early administration of abciximab in acute ST-segment elevation
      myocardial infarction in the emergency room.
AB  - OBJECTIVE: Abciximab, a platelet glycoprotein IIb/IIIa inhibitor, administered in
      conjunction with primary coronary stenting, improves the outcome of acute
      myocardial infarction, and the earlier it is administered, the greater the
      improvement. We sought to assess the feasibility of early administration of
      abciximab in the emergency room (ER) before primary coronary stenting and compare
      our results with those of a group of patients treated in the prehospital
      (ambulance) phase. METHODS: Data and outcome of patients with acute ST-segment
      elevation myocardial infarction who received abciximab (0.25 mg x kg(-1) then
      0.125 mg x kg(-1) x h(-1)) in the ER before primary coronary stenting were
      compared with those of patients who received abciximab in the prehospital phase.
      RESULTS: Characteristics of the group treated in the ER did not differ
      significantly from those of patients treated before arrival at the hospital,
      except for prevalence of diabetes (22 versus 5%, p<0.05) and administration of
      analgesic to control chest pain (22 versus 65%, p<0.05). Nor did the median time
      between onset of pain and abciximab administration differ significantly different
      (120 versus 160 min, NS). In contrast, the median delay between the beginning of
      abciximab administration and insertion of the cardiac catheter was significantly
      shorter in the ER group (35 versus 55 min, p<0.05). There were no significant
      differences between groups in TIMI flow grade before or after revascularization,
      specific revascularization performed, or outcome. CONCLUSION: Our study provides
      some evidence that early administration of abciximab in the ER is safe, feasible,
      and justified by the delay required for coronary revascularization.

PMID- 16462664
TI  - [Crohn disease and abdominal tuberculosis: complications related to a diagnostic
      error].
AB  - INTRODUCTION: We report the case of a patient with abdominal tuberculosis
      initially treated as Crohn disease. CASE: A 50-year-old man, diagnosed with Crohn
      disease, was admitted to the intensive care unit for acute respiratory failure.
      After a new diagnosis of pulmonary and ileocecal tuberculosis and appropriate
      treatment for it, he improved. DISCUSSION: It is difficult - but essential - to
      differentiate intestinal tuberculosis and Crohn disease, for the immune
      suppression necessary to treat the latter can induce severe complications of the
      former. Management of intestinal tuberculosis is primarily medical, with surgery
      reserved for complications such as obstruction, fistulization, perforation, and
      bleeding.

PMID- 16462665
TI  - [Multiple basal cell carcinomas following radiation therapy for nasopharyngeal
      cancer].
AB  - INTRODUCTION: Basal cell carcinoma (BCC) is a cutaneous, generally primary
      malignancy, most common among the elderly. We report the case of a patient
      presenting numerous BCCs several years after radiation therapy for nasopharyngeal
      cancer and discuss the risk factors for this tumor and the role played by
      radiation in its genesis. CASE: A 30-year-old woman presented with pigmented
      facial lesions that had been developing over the past year. Eleven years earlier,
      she had had an undifferentiated nasopharyngeal carcinoma (T3N2M0), which was
      treated by neoadjuvant chemotherapy and then external radiation therapy. Initial
      cutaneous examination noted two lesions that were identified as BCC after biopsy.
      The tumors were excised surgically. Neither clinical nor radiological check up
      showed signs of basal cell nevus syndrome. DISCUSSION: BCC is the most frequent
      malignant tumor. It is observed mainly among those aged 45-60 years. Disorders
      that might promote or complicate BCC should be systematically sought in young
      patients, especially basal cell nevus syndrome. While our patient may have had
      this syndrome, we found none of the other clinical or radiographic elements often
      observed with it. The occurrence of BCC within the irradiation area, the
      multiplicity of lesions, and the sufficient latency period are consistent with
      radiation-induced tumors. We found no reports in the literature of BCC following
      radiation treatment for nasopharyngeal cancer, but the occurrence of these tumors
      in our patient suggests the need for close supervision in such cases.

PMID- 16462666
TI  - [Thrombocytosis: adverse effect of heparin treatment].
AB  - INTRODUCTION: Thrombocytosis induced by heparin is rarely reported in the
      literature. CASE: We report here four cases of thrombocytosis, three in patients
      under treatment for a stable myeloproliferative disorder. Thrombocytosis always
      regressed when heparin treatment was discontinued, and no thrombotic events
      occurred. DISCUSSION: Following several reports suggesting an association between
      heparin and thrombocytosis, the French adverse drug reporting (pharmacovigilance)
      network identified 51 cases. Thrombocytosis associated with heparin is probably
      explained by the latter's potentiation of megakaryocytopoiesis, in particular, by
      inhibition of platelet factor 4 (PF4). Thrombocytosis is a further reason to
      monitor platelet counts during heparin treatment.

PMID- 16462667
TI  - [Acute renal failure following mucosal administration of povidone iodine].
AB  - INTRODUCTION: Povidone iodine is a widely-used antiseptic agent, especially for
      cutaneous lesions. Despite its apparent innocuousness, some cases of acute renal
      failure are reportedly due to iodine toxicity. CASE: We report a case of an acute
      renal failure secondary to povidone iodine exposure in a 37-year-old woman. She
      underwent a hysteroscopy for diagnosis of primary sterility, and povidone iodine
      was used as the contrast agent. She developed acute renal failure with oliguria
      during the postoperative period. Treatment with diuretics and hemodialysis led to
      a favorable outcome and return of normal kidney function. DISCUSSION: Mucosal
      administration of povidone iodine appears to lead to greater iodine toxicity than
      cutaneous administration. The clinical feature of our patient suggested tubular
      necrosis caused by iodine, after the other possible causes of acute renal failure
      were ruled out. CONCLUSION: Acute renal failure secondary to povidone iodine
      administration is possible, especially through mucosal surfaces. Outcome is
      favorable after the conclusion of exposure and symptomatic treatment.

PMID- 16462669
TI  - [Pigmented villonodular synovitis of the knee].

PMID- 16462668
TI  - [Meningitis caused by Enterococcus faecalis during disseminated anguilluliasis].
AB  - INTRODUCTION: Disseminated anguilluliasis is a serious disease requiring early
      diagnosis and treatment. The occurrence of bacterial complications, especially
      meningeal, is generally due to Gram-negative bacteria from the gastrointestinal
      tract. CASE: A 52-year-old man from Guadeloupe, treated for T-lymphoma during the
      previous year by polychemotherapy, was hospitalized for meningitis. Culture of
      the cerebrospinal fluid and the bronchoalveolar lavage both showed Enterococcus
      faecalis. Strongyloides stercoralis were also found in the stool and
      bronchoalveolar lavage. Outcome under treatment was favorable. DISCUSSION: This
      case reminds us of the usefulness of presumptive routine ivermectin treatment for
      all patients exposed to any immunosuppression treatment and ever having lived in
      a tropical area and thus possibly infected by chronic but silent anguilluliasis,
      even in the absence of parasitological certainty.

PMID- 16462670
TI  - [Gifted children or children at risk?].

PMID- 16462671
TI  - [Gifted children and the family physician].
AB  - Gifted children account for about 2% of the population but are not always
      identified. Nonsynchronous intellectual, biological and affective development may
      cause problems and disrupt relationships at home and in school. GP's are
      consulted for mood or behavior disorders or somatization. If maladjustment at
      school appears to be related to mood or behavior disorders, a complete
      psychological assessment is essential. It is especially important to rule out the
      differential diagnosis of ADHD because of the differences in treatment. A
      substantial portion of management depends on teachers and the overall school
      environment. GP's are involved in long-term support of children and families, and
      in treatment of related disorders: depression, anxiety, sleep disorders, and
      somatization. Drug therapy has a very limited role in treatment of related
      disorders.

PMID- 16462672
TI  - [Medication and memory: interactions among the elderly].
AB  - Several different systems govern human memory, and different drugs may act
      specifically on one or more of them. The central nervous system in the elderly is
      particularly sensitive to drugs, and an iatrogenic cause must be sought for all
      recent and/or sudden alterations in memory functions. In the case of recent
      alterations in memory, all nonessential drugs, especially psychotropic agents;
      should be withdrawn or reduced. Elderly persons, especially those with dementia,
      are at risk because of the frequent and substantial effects of drugs on their
      memory: the benefit-risk ratio must be evaluated regularly and essential
      treatments maintained.

PMID- 16462675
TI  - [New data about eosinophilia and people who have it].

PMID- 16462674
TI  - [Antiretroviral drugs in severe acute respiratory syndrome].
AB  - Inhibition of viral assembly (protease inhibitors) and of fusion of viral and
      target membranes (fusion inhibitors) are general approaches to antiviral
      treatment, not specific for HIV. Nonetheless, the agents that induce these
      phenomena are most often specific for a given virus or virus family. Drugs
      developed for HIV treatment were reevaluated for use against severe acute
      respiratory syndrome-coronavirus (SARS-CoV) during and after the epidemic in
      2003, in view of the absence of any other available treatment. Of the protease
      and entry inhibitors approved for treating HIV-infected patients, none was
      effective against SARS-CoV, although in vitro activity against this virus was
      reported for the protease inhibitor lopinavir/ritonavir, in results that have not
      been confirmed in the most recent studies. The epidemiologic methods used to
      assess this drug's efficacy are not robust. Preliminary results for SARS
      treatment with protease and entry inhibitors, although at early stages of
      development, are promising.

PMID- 16462676
TI  - [Eosinophils: structure and functions].
AB  - Long considered to be secondary cells characterized mainly by their ability to be
      recruited to inflammation sites, these cells are now known to release a wide
      array of cytotoxic mediators. Moreover they participate in immune response
      regulation by producing Th1 and Th2 cytokines as well as regulatory cytokines and
      chemokines. This review describes recent findings about their expression of
      surface molecules, eosinophil mediators, and the role of both in these novel
      eosinophil functions.

PMID- 16462673
TI  - [Consultation after cerebral infarction or intracerebral hematoma].
AB  - Hypertension is the principal risk factor for cerebral infarctions and
      intracerebral hematoma. The brain is the principal target of hypertension. The
      brain is the principal target of antihypertensive drugs. Controlling blood
      pressure and stopping smoking reduces the risk of cerebral infarction by 40%.
      Objectives of a consultation after cerebral infarction or intracerebral hematoma:
      validate diagnosis and cause, identify risk factors for recurrent cerebral
      infarction but also for myocardial infarction and lower limb arterial disease,
      begin treatment of the risk factors for recurrence, begin prevention of
      atherothrombotic complications and embolic heart disease, identify complications
      of cerebral infarction and intracerebral hematoma.

PMID- 16462677
TI  - [Activated eosinophils: techniques to characterize them].
AB  - The deleterious role thought to be played by eosinophils in many situations is
      linked to their ability to secrete various inflammatory substances, mainly toxic
      proteins and lipid mediators, in body tissue. This ability is a particular
      feature of activated eosinophils, which have undergone numerous metabolic,
      functional, and phenotypic changes from their resting state. Characterizing the
      properties of these activated cells is an essential step in improving our
      understanding of their contributions to local inflammatory response, as both
      regulatory and effector cells. Improvements in existing methods as well as the
      development of new technical approaches have facilitated the ex vivo and in vitro
      study of activated eosinophils and their contribution to various disease states.

PMID- 16462678
TI  - [Allergy-related hypereosinophilia].
AB  - Hypereosinophilia in the blood and tissues is one of the main characteristics of
      the pathophysiology of allergic disease. CD4+ T cells polarized to a Th2
      phenotype mediate inflammatory disorders; cytokines produced by Th2, including IL
      4, IL-5, and IL-13, drive the cardinal features of the disease. Recent human
      experiments indicate that eosinophils may control the bronchial remodeling that
      occurs in asthma. Eosinophils are a rich source of fibrogenic factors,
      particularly TGF-ss. Atopy is defined by abnormal IgE production in response to
      an allergen (an antigen that is then designated an allergen). Allergy combines
      pre-existent sensitization (atopy) with various symptoms - cutaneous, ENT,
      respiratory, or digestive. Atopy is diagnosed primarily by cutaneous skin-prick
      tests and the new multi-allergen blood test. A diagnosis of allergy requires the
      presence of symptoms and justifies workups for asthma, rhinitis, food allergies,
      or atopic dermatitis.

PMID- 16462679
TI  - [Diagnosis of non-parasitic hypereosinophilia].
AB  - Diagnosis of major hypereosinophilia (>1500 x 10(9)/L) is complex because the
      possible causes cover the entire range of medical specialties. History and
      clinical condition will usually suggest parasitic or allergic diseases or drug
      reactions. When workups for them are negative, rarer causes must be suspected:
      specific organ diseases (chronic eosinophilic pneumonia, bullous pemphigoid,
      etc.), solid tumor, clonal blood disorders, or vasculitis. When the condition is
      prolonged and unexplained, hypereosinophilic syndrome is diagnosed. A rare
      disorder, its prognosis depends on largely on its cardiac effects. It is usually
      associated with heterogeneous hematologic conditions, mainly myeloproliferative
      and lymphocytic disease. The myeloproliferative or primary variant sometimes
      follows chromosomal deletions that cause a fusion between the Fip1-like1 (FIP1L1)
      and platelet-derived growth factor receptor (PDGFR) genes, thus increasing the
      tyrosine kinase activity of the latter. Imatinib mesylate, a tyrosine kinase
      inhibitor, is usually effective in this situation. In the lymphocytic variant,
      hypereosinophilia is secondary to a primitive Th2 lymphocyte expansion that
      causes overproduction of interleukin 5 (IL-5). Corticosteroids are the first-line
      therapy. Mepolizumab, an anti-IL-5 monoclonal antibody, currently being
      evaluated, seems promising. Despite recent progress, about 40% of the cases of
      hypereosinophilic syndrome remain unexplained.

PMID- 16462680
TI  - [Parasite-induced hypereosinophilia].
AB  - Blood hypereosinophilia (eosinophilia count of more than 500 per microliter,
      i.e., 0.5.10(9)/L) is a laboratory finding that requires a careful workup. Review
      of the patient's medical history and clinical examination can usually rule out
      non-parasitic causes. Parasitic infections must be sought by examination of
      stool, urine, and blood examinations and by serological tests. These
      examinations, with special techniques for cosmopolitan and tropical parasites and
      for digestive or tissular parasites, must be repeated. Improvement of blood
      eosinophilia and of the serum antibody titers is one criterion of treatment
      effectiveness.

PMID- 16462682
TI  - [Aneurysmal bone cyst of the tibia].

PMID- 16462681
TI  - [Treatment of hypereosinophilia].
AB  - Therapeutic management of blood hypereosinophilia depends on its underlying
      cause. The cause may be clearly established (parasitic infestation) or more
      hypothetical (systemic disease). Blood eosinophils often return to normal levels
      after treatment of either the cause or the associated eosinophilic disease. A
      targeted approach is more difficult when the cause is unknown (unexplained
      chronic hypereosinophilia). Various conventional treatments (corticosteroids,
      hydroxyurea, interferon) have been somewhat effective. The identification of new
      cellular and molecular markers with diagnostic and pathophysiologic significance
      makes more rational approaches possible.

PMID- 16462683
TI  - [Cognitions in eating disorders and their assessment].
AB  - Cognitions are of crucial importance in the -aetiology and the maintenance of
      eating disorders. Dysfunctional cognitions in eating disorders are related to
      body image, self-esteem and feeding. The aim of this paper is to review the
      actual knowledge in this area. First, we will display -cognitive models in eating
      disorders. Cognitive factors in -eating disorders are logical errors, cognitive
      slippage and conceptual complexity. Eating disorder patients seem to have a
      deficient cognitive development. Some cognitive models stipulate that eating
      disorder patients may develop organised cognitive structures schemas concerning
      the issues of weight and its implications for the self. These schemas can account
      for the persistence and for the understanding the "choice of the eating disorder
      symptomatology. Cognitive pheno-mena of interest are self-schema, weight-related
      schema and weight-related self-schema. The maintenance model of ano-rexia nervosa
      argued that, initially there is an extreme need to control eating which is
      supported by low self-esteem. The maintenance of the disorder is reinforced by
      three mechanisms: dietary restriction enhances the sense of being in control;
      aspects of starvation encourage further dietary restriction; concerns about shape
      and weight encourage restriction. The development and maintenance of bulimic
      symptomatology are explained by placing a high value on attaining an idealised
      weight and body shape accompanied by inaccurate beliefs. The cognitive model of
      specific family of origin experiences puts forward the development of 
      maladaptative expectancies for eating and thinness. Second, we discuss
      distortions in information processing. a) In feeding laboratories, bulimics show
      a wide range of caloric intake and a disruption of circadian feeding patterns. In
      overeating bulimics, large meals occurred mainly during afternoon and evening
      with high fat and carbohydrate intake, but the majority of meals were of normal
      size and frequency. Responsivity to food cues indicates that bulimics were more
      responsive to sight, smell and taste of their favourite binge food, and a greater
      responsivity was associated with increasing -cue salience. Eating disorder
      patients appear to have internalised a mediated social rule concerning "good
      food" and make drastic selections thus removing the possibility of choice of
      foodstuffs. b) Experimental processes: temporal factors in the processing of
      threat seem to be of importance in patients with high levels of eating
      psychopathology. There is no evidence for preattentive processing biases among
      anorectics. Changes in information processing speed after treatment were not
      linked to treatment condition or treatment response. c) Judgement and emotions:
      in eating disorder patients, distortions of depressogenic nature are found that
      influence the cognitive style; thoughts about eating, weight and shape are
      characterised by negative affective tone; negative emotions could account for
      bulimic behaviour; anxiety and distress are correlated to thought control
      strategies. Information treating seems to be impaired in a non-homogeneous way.
      d) Cognitive schemas are seriously maladaptive and not well investigated. In
      eating disorder patients, core beliefs are absolute, unconditional and
      dichotomous cognitions about oneself and the world. There are only few studies in
      this field moreover showing controversial results. Core beliefs can explain links
      between personality disorders and eating psychopathology. Pathological core
      beliefs have to be taken in to account because they influence the outcome and the
      efficacy of cognitive behavioural therapy. Third, the last part of this paper
      summarises actually available rating scales eva-luating distorted cognitions in
      eating disorders. There are different methods for evaluation: specific and non
      specific self-report questionnaires, thought-sampling procedures, -methods
      derived from cognitive psychology. The Mizes Anorectic Cognition questionnaire
      (MAC) is a well-known self-rating scale with good psychometric properties. The
      revised form of the MAC appears to be an improvement in the area of internal
      consistency, sensitivity, and reliability. It is obvious that there is no
      particular rating scale referring to specific cognitions on food. IN CONCLUSION:
      the main result of this literature review reflects that the cognitive treatment
      in eating disorders is altered in a specific way on an emotional basis and on
      self-representation.

PMID- 16462684
TI  - [Transversal study of the psychosocial rehabilitation and the quality of life of
      75 schizophrenics under classical neuroleptics or atypical antipsychotic
      neuroleptics].
AB  - The psychosocial rehabilitation and the quality of life of schizophrenics have
      constituted the main concern in the taking care of these patients since their
      return into our society. Thus, the emergence of atypical neuroleptics allows us
      to imagine very interesting and important perspectives concerning these 2
      concepts. The adaptation to social and professional life, and the quality of life
      have been rarely compared according to the antipsychotic therapeutic used
      (classical neuroleptics or atypical neuroleptics). As many authors underline it,
      there are still very few studies undertaken concerning this subject because of
      the diverse methodological and ethical limitations implied. That is why we
      established a transversal study of the psychosocial adaptation and of the quality
      of life of 2 stabilized schizophrenic groups. These 2 different groups are: the
      NC group under classical neuroleptics on the one hand, and the NA group under
      atypical neuroleptics on the other hand. The main target of this study is to
      observe the influence of the atypical neuroleptics independently of the other
      factors. Three evaluation scales were used: the PANSS, the psychosocial skill
      scale (EAPS) of G. Darcourt and the French translation by P. Martin of the
      Functional Statut Questionnaire (FSQ), and a collection of the clinical and
      therapeutic socio-demographic data. Concerning the psychosocial capacities, the
      total results revealed one significant difference (p-value<0.01) between the two
      groups. The NA group showed a better psychosocial adaptation (80 +/- 10.89 versus
      72 +/- 13.39). Besides 4 key-domains are statistically different, but are always
      in favour of the NA group; the domains are family life (p=0.01), social life
      (p=0.0026), presentation (p=0.003) and housing and food (0.029). These
      observations incite to modify our cure. The analysis of the total score of the
      FSQ did not reveal a statistically significant difference between both groups but
      this total score seems high in both groups, conveying an important feeling of
      satisfaction about the quality of life of our sample of schizophrenics.
      Literature data also abound along the same lines. Indeed, authors underline that
      patients clearly prefer to live outside rather than in the hospital. Besides,
      this study allows to confirm the literature data while studying some domains
      (such as sexuality) rarely brought to light in studies. As a conclusion, we can
      say that our sample is representative of a population of schizophrenics, and in
      spite of the difficulties of methodology inherent to this type of study, we can
      make a comparison between our 2 groups thanks to the stu-died data. Data in which
      differences could be found, did not show any influence on the results of scales,
      thus, they cannot be considered as a confounding factor. The NA group showed a
      better psychosocial adaptation. Furthermore the FSQ did not reveal a difference
      between both groups. It seems important to remind that a prospective study,
      conducted for several months and with several evaluations, is essential to
      confirm the results obtained on both types of treatment.

PMID- 16462685
TI  - [Is age at onset associated with executive dysfunction in obsessive-compulsive
      disorder?].
AB  - In obsessive-compulsive disorder (OCD), clinical, neurobiological and genetic
      differences have been reported according to age at onset (AAO). Given the
      importance of identifying homogeneous subtypes in complex hete-rogeneous
      disorders such as OCD, it would be particularly useful to identify a specific
      cognitive profile associated with early-onset OCD. Although impaired cognition
      has repea-tedly been demonstrated in OCD patients, discrepancies between studies
      have hampered the identification of a precise cognitive dysfunction. Executive
      dysfunction has often been reported, but findings have not always been
      replicated. The aim of this study was to assess executive functions in 30
      patients according to their AAO. The sample consisted of 15 early-onset and 15
      late-onset OCD patients and 22 normal controls, matched for age, sex and socio
      economic status. Various aspects of executive function were assessed with five
      neuropsychological tests: Tower of London, Trail Making Test, Verbal Fluency,
      Design Fluency and Association Fluen-cy. The 30 OCD patients obtained lower total
      scores than the controls in the Tower of London test and association fluen-cy
      task (p<0.05 and p<0.001, respectively). Impairments were more marked for the
      early-onset group, with no effect of gender or age at interview. Deficits in
      specific aspects of frontal lobe function were found in the OCD group and were
      particularly pronounced within the early-onset group. These findings confirm
      clinical data suggesting that OCD patients can be subtyped according to age at
      onset and that OCD patients present unusual cognitive characteristics. They also
      support the hypothesis that early-onset OCD might be a rele-vant subgroup
      characterised both by a particular clinical profile and by specific cognitive
      characteristics.

PMID- 16462686
TI  - [Emotional processes in schizophrenia: investigation of the evaluative
      component].
AB  - Schizophrenia is a disease that constitutes a particularly relevant way to
      investigate emotional processing. Indeed, major clinical signs of emotional
      disturbance (eg, anhedonia) suggest that some emotional mechanisms are defective
      in patients with schizophrenia. Evaluation can be considered as a fundamental
      component of the emotional system (28) and the first aim of the present study was
      to test the polarity hypothesis according to which different mechanisms are
      involved in the evaluation of positive vs negative emotional events. The second
      aim was to disentangle a -paradox emerging from the schizophrenia literature. On
      one hand, the tendency that schizophrenic patients have to under-evaluate the
      level of unpleasantness of negative stimuli suggests a deficit in the evaluation
      of negative events. For instance, it was proposed that patients with
      schizophrenia show a major deficit in the recognition of negative emotions, but a
      preserved recognition of positive emotions. On the other hand, the fact that
      anhedonia constitutes a critical cli-nical feature of schizophrenia suggests a
      deficit in the eva-luation of positive events. For instance, Crespo-Facorro et
      al. showed that patients with schizophrenia had a tendency to under-evaluate the
      level of pleasantness of positive stimuli but correctly evaluated the level of
      unpleasantness of negative stimuli. Given the importance of the social component
      in the analysis of deficits in patients with schizophrenia, we hypothesized that
      the variation of this component in stimuli used in the literature could explain
      the apparently inconsistent results described above. For example, the Bell et al.
      study used social stimuli whereas the Crespo-Facorro et al. study used non-social
      stimuli. Therefore, in our study, we have decided to manipulate the social
      component of stimuli. Another research issue of the present experiment was to
      study the explicit and/or implicit mode of processing of eva-luation in
      schizophrenic patients. In general, the experimental logic was to expect
      interaction effects between the factors polarity (negative vs positive) and
      participants (schizophrenic patients vs controls). Moreover, given the potential
      importance of the social component, a three-way interaction of the factors
      polarity, participants, and social component was expected. Finally, the
      experimental paradigm allowed us to search for dissociations in the context of
      both explicit and implicit evaluation. Stimuli used were negative and positive
      emotional pictures from the International Affective Picture System. Stimuli were
      chosen so that the mean valence -ratings of negative and positive pictures were
      at the same distance from neutrality. The factor arousal was controlled so that
      negative and positive pictures had equivalent mean arousal ratings. The social
      component factor was operatio-nalized by selecting pictures that either depicted
      or not a social scene. A fundamental criterion was that all social pictures were
      depicting at least one human being (eg, a wedding or a funeral), whereas non
      social pictures never depicted any human being (eg, animals and landscapes). An
      upper and a lower border, that were either identical or different, were added to
      each picture. In a first experiment (the "implicit-task experiment"), patients
      with schizophrenia and matched controls were requested to decide whether the two
      borders surrounding the pictures were identical or different. Asking participants
      to process the borders was an experimental ruse to test if emotional processing
      takes place even when it is not task-relevant, and therefore if it is implicit.
      In a second experiment (the "explicit-task experiment"), the same participants
      were requested to evaluate whether the pictures were pleasant or unpleasant.
      Analyses of variance (ANOVA) were computed on response time and number of correct
      responses for both tasks. An important result was the observation of the expected
      three-way interaction effect of the factors polarity, participants, and social
      component on response time in the explicit task F(1, 19)=4.8, p<0.05. Critically,
      we observed that, for non-social stimuli, the interaction effect of the factors
      participants and polarity on response time was significant in the explicit task,
      F(1, 8)=4.9, p<0.05. These results are consistent with the polarity hypothesis
      and suggest a deficit in the processing of non-social positive stimuli in
      patients with schizophrenia. The expected three-way interaction effect was also
      observed on the number of correct responses in the explicit task F(1, 19)=5,
      p<0.04. For this task, we critically observed that, for social stimuli, the
      interaction effect of the factors participants and polarity on the number of
      correct responses was significant F(1, 19)=8.4, p<0.04. These results are also
      consistent with the polarity hypothesis and suggest a deficit in the processing
      of social negative stimuli in patients with schizophrenia. Moreover, let us
      notice that a comparison of the performances of the two groups revealed that
      patients made significantly more errors than controls for the evaluation of non
      social positive stimuli, F(1, 19)=10,5, p<0.001, but not for the evaluation of
      non-social negative stimuli, F<1. In the implicit-task experiment, the analysis
      revealed that patients had a tendency to make more errors in the judgment of
      borders configuration for negative than for positive stimuli, whereas control
      participants showed the opposite tendency F(1, 19)=5.7, p<0.03, for the
      interaction of the factors polarity and participants. This result is consistent
      with the idea that distinct cognitive mechanisms are involved in the evaluation
      of positive vs negative emotional events even in the context of implicit
      processing. In conclusion, results obtained support the hypothesis according to
      which different cognitive mechanisms are involved in the evaluation of positive
      vs negative emotional events. Moreover, results suggest that patients with
      schizophrenia show a deficit in hedonic judgment of social negative and non
      social positive stimuli. The later result indicates that the paradox described
      above becomes clearer whenever the social component of emotional stimuli happens
      to be taken into account. Results suggest that the polarity and the social
      component of events evaluated by patients with schizophrenia are critical
      parameters that should be considered in forthcoming studies that investigate
      affect disorders in schizophrenia.

PMID- 16462687
TI  - [The study assessed the prevalence of TPS and its associations with psychopathy
      in a population of forensic violent patients in a Belgian security hospital].
AB  - The population was composed of 76 male patients (mean age=36.14). All of them
      having committed a violent offence indexed in their institutional file: (1)
      sexual offences on children; (2) rapes of adult women; (3) homicide offence; and
      (4) assaults and batteries. TPS was defined by the following 8 diagnostic
      criteria as described in DSM III-R: 1) has used physical cruelty or violence for
      the purpose of establishing dominance in a relationship; 2) humiliates or demeans
      people in the presence of others; 3) has treated or disciplined someone under his
      or her control unusually harshly; 4) is amused by, or takes pleasure in, the
      psychological or physical suffering of others; 5) has lied for the purpose of
      harming or inflicting pain on others 6) gets other people to do what he or she
      wants by frightening them 7) restricts the autonomy of people with whom he or she
      has a close relationship; 8) is fascinated by violence, weapons, martial arts,
      injury, or torture. These criteria were assessed from (a) clinical and
      institutional files and (b) clinical collateral informations. TPS assessment was
      conducted by two -trainees in clinical psychology (kappa=0.87; n=20). The
      assessment of psychopathy was conducted according to the guidelines of the Hare
      psychopathy checklist manual (PCL-R, 1991, 2003): coding of clinical and
      institutional files and semi-structural clinical interviews. The PCL-R is mainly
      composed by 2 factors: factor 1 "Emotional detachment" describing the core
      psychological component of psychopathy, and factor 2 "Chronically antisocial
      factor" reflecting behavioral instability and antisocial life style. The total
      cut-off score for the inclusion of the diagnosis was 25. The prevalence of TPS in
      the population was 25% (n=19) and is congruent with the large range described in
      the literature (0.5 to 33%). The most frequent criteria were 6 (gets other people
      to do what he or she wants by frightening them), 1 (has used using physical
      cruelty or violence for the purpose of establishing dominance in a relationship)
      and 3 (has treated or disciplined someone under his or her control unusually
      harshly). The most sensible criteria were: 7 (restricts the autonomy of people
      with whom he or she has a close relationship), 8 (major interest for violence)
      and 4 (pleasure in the psychological or physical suffering of others). The most
      specific criteria were: 3 (has treated or disciplined someone under his or her
      control unusually harshly), 6 (gets other people to do what her or she wants by
      frightening them), 4 (takes pleasure in the psychological or physical suffering
      of others) and 1 (has used physical -cruelty or violence for the purpose of
      establishing dominance in a relationship). As concerns psychopathy, the mean of
      factor 1, factor 2 and the PCL-R total scores were 7.40, 9.08 and 18.67. Thus,
      38% of patients were considered as "low psychopaths", 36% were considered as
      "moderate psychopaths" and 26% were considered as "high psychopaths". In spite of
      few significant positive correlations between some TPS and PCL-R criteria, TPS
      diagnosis was not significantly correlated with factors 1, factor 2, nor with
      total score of the PCL-R. The mean psychopathy total score did not differ between
      sadistic and non-sadistic patients. Moreover, a two ways ANOVA comparing PCL-R
      factors 1 and 2 did not reveal any differences between sadism and non-sadism.
      Again, these comparisons did not support hypothesis of a strong association
      between TPS and psychopathy.

PMID- 16462688
TI  - Analysis of differential clinical profiles of different antipsychotic molecules
      in the first psychotic episode: a retrospective study.
AB  - Our study starts from the supposition that the ideal pharmacological treatment
      should improve the patient's global behaviour, as a consequence of the
      therapeutic activity on positive, negative, behavioural, affective and cognitive
      symptoms. It should have few secondary effects, both in the short and long term,
      thus assuring a good life-quality, the fundamental condition for the patient's
      compliance and adherence. Currently only few studies have been published
      evaluating atypical antipsychotic effects vs. typical ones in the first psychotic
      episode, particularly studying different profile evaluations and different
      molecule rating standards. Our aim has been the therapeutic profile evaluation of
      atypical anti-psychotic molecules vs. typical ones, using "Liege's star"
      parameters (anti- manic, anti-autistic, anti-delusional, extra-pyramidal,
      ataraxic-sedative and adrenolitic). We added 2 complex scales, the first for loss
      in affectiveness, the second for cognitive and behavioural disorganization. We
      utilized Aosta's Psychiatric Service data-base, evaluating patients in their
      first psychotic episode diagnosed with various schizophrenic disorders per DSM IV
      criteria. We considered everyone who received, as monotherapy, or a typical
      molecule or an atypical one and who had been tested, at the beginning and at the
      end of the psychotic episode, with MMPI and PANSS Rating Scale. We evaluated 107
      patients, 68 men and 39 women, whose mean age was 25,04 years (SD=3,789): 21
      schizo-affective, 27 schizophreniform, 23 brief reactive psychosis and 36
      paranoid- type schizophrenic disorders. The mean observation time was 117,18
      days. Monotherapy was with olanzapine (23), quetiapine (8), risperidon (19),
      haloperidol (20), clopentixol (9), chlorpromazine (10), pimozide (8) and
      sulpiride (10). For the evaluation of adrenolitic, sedative and extrapyramidal
      effects we utilized clinical data and specific drugs administrations. We based
      our estimate for anti-delusional activity on P1, p3, p4, p5, p6, p7, g9 and g12
      PANSS items score, correlated with Se and Pa MMPI results; for anti- autistic
      activity 2,3 and 4 PANSS items score related with MMPI Si Scale; for activity on
      behavioural and cognitive symptoms p2, n5, n6, n7 PANSS items score; for activity
      on negative symptoms PANSS negative global score. From the MMPI score we
      evaluated aggressiveness, hypochondria, negative symptoms, depression and
      psychasthenia. Our trial results hypothesise that neuroleptic anti-deficitary
      activity develops itself on different, qualitative and chronological levels: a
      continuous pathway from the original stimulus, through a dis-inhibiting effect to
      a final anti-autistic effect it would cause a deficit reduction. We haven't seen
      considerable differences between typical or atypical molecules perform inhibiting
      activity on D2 receptors. It seems that atypical molecules specific activity on
      D1, D3 and D4 receptors (affinity) and on 5HT2 receptors (inhibition) comes out
      as negative symptoms improve. We can say, too, that, according to compliance,
      adherence and concordance parameters, atypical molecules improve patient's life
      quality through a good treatment and a real therapeutic alliance. Finally, we
      have seen that therapies with atypical molecules increase the family's
      satisfaction and compliance.

PMID- 16462689
TI  - [Management strategies for major depressive episodes as a function of initial
      response to an SSRI or SNRI antidepressant: results of the ORACLE survey].
AB  - OBJECTIVE: The main aim of the major depressive episode treatment is to obtain a
      complete remission. However, partial remission (persistence of residual symptoms)
      is a frequent outcome of major depressive episodes, concerning approximately half
      of the patients who were responders to the treatment. An inadequate treatment
      response after three weeks of treatment is considered by the ANAES
      recommendations as a potential reason to modify the treatment regimen. The
      primary objectives of this survey were to describe the therapeutic strategies
      implemented in subjects treated as outpatients for a major depressive episode
      following evaluation of the initial response to an SSRI or an SNRI antidepressant
      and to assess by a naturalistic way the impact of these strategies on the extent
      of remission at three months. The secondary objective was to determine, by
      multivariate analysis, others factors able to influence the remission. METHODS:
      This prospective observational survey concerned 2 138 patients treated by
      community psychiatrists (n=582) and presenting a major depressive episode in the
      context of a recurrent depressive disorder. Patients were assessed at inclusion
      and at Weeks 3, at Week 6 and at Week 12. Changes in score on the Hamilton
      Depression Scale (Ham-D) and CGI severity between inclusion and Week 3 and
      improvement scores were evaluated. The therapeutic strategies after evaluation
      were described. Remission was defined as a score of 1 or 2 on the CGI-improvement
      scale; a treatment response at Week 3 was defined as a decrease of at least 50%
      in the Ham-D score. The physician also provided an overall rating of satisfaction
      with the treatment at Week 3. RESULTS: Data from 1 974 patients were analysed.
      The mean age at inclusion was 42.7 years, 70% of the patients were women; the
      mean age at first episode was 32.2 years, the average time since the last episode
      was 3.6 years. The mean Ham-D score at inclusion was 23.6 +/- 5.8. At Week 3,
      29.1% of patients were considered treatment responders. The antidepressant dose
      was subsequently increased in 10.2% of responders compared to 36.3% of non
      responders. When the physician rated the treatment response as unsatisfactory,
      the dose was increased in 56% of cases. At week 12, 83.7% of patients were in
      remission as defined by the CGI; according to physician judgement, 45.7% were in
      complete remission and 43.3% in partial remission. According to the literature,
      the existence of an early response to the treatment predicted a total remission
      at Week 12 (69.1% of the treatments responders at Week 3 were in complete
      remission at Week 12, vs 35.7% of the treatments not-responders). CONCLUSION:
      These results underline the professional practices in private community
      psychiatric practice in France. At Week 3, posology increased for only 36.3% of
      the patients, whereas it is one of the therapeutic strategies recommended by the
      ANAES. Participating physicians relied on their subjective judgement about
      initial treatment response when making decisions about treatment strategies
      rather than by psychometric scores. At Week 3, 29.1% of patients were considered
      treatment responders according to the change in Ham-D score, compared to 57.3%
      whose treatment response was considered satisfactory by the physician. The
      decision to increase the dose was more closely associated with subjective
      perceptions of satisfaction than with psychometric rating scale scores, despite
      psychometric evaluation was systematic in the ORACLE survey, what is not the case
      in usual practice in France, except for clinical research. In addition, this
      study confirms an important data for the clinician: there is a correlation
      between early response to the treatment (Week 3) and complete remission at the
      end of the acute phase of treatment (Week 12).

PMID- 16462702
TI  - Update on growth, reproduction and endocrine complications in thalassaemia.
      Proceedings of the 9th International Conference on Thalassaemia and
      Haemoglobinopathies. October 15-19, 2003. Palermo, Italy.

PMID- 16462690
TI  - [Acute catatonic syndrome after neuroleptic malignant syndrome].
AB  - We report the case of a young woman who deve-loped catatonic syndrome a few days
      after neuroleptic mali-gnant syndrome (NMS), arising the problem of the
      chronology of both affections. A 20-year old woman with an history of bipolar
      disorder, experienced an acute manic syndrome that made hospitalization
      necessary. Fourteen days after loxa-pine prescription, the patient developed a
      NMS (DSM IV criteria) dyskinesia, dysphagia, fever and alteration of cons
      ciousness. Hepatic transaminases and muscular enzymes increased. Neuroleptic was
      immediately interrupted and benzodiazepines (Lorazepam) was started. Biological
      parameters were normalized after 7 days, hyperpyrexia decreased and
      extrapyramidal symptoms disappeared but manic symptoms persisted. Two weeks
      later, the patient presented nega-tivism, rigidity of the four limb, catalepsia
      and hyperpyrexia. She also had been anxious for death and presented auditory
      hallucinations. Bacteriological samples and computed tomography were normal. This
      catatonic symptoms did not decreased and electroconvulsive therapy (ECT) was
      necessary. After six ECT, she started standing up, walking, taking food and
      speaking. After 12 ECT, the clinical state was the same as it was before the
      acute episod. The patient was then treated with valproate and lorazepam for
      anxiety symptoms. Acute catatonie, a rare and life-threatening acute syndrome was
      described in psychosis before the advent of neuroleptic drugs. It's characterized
      by hyperexia, stupor alternated with exctement, rigidity. Many etiolologic
      factors have been reported for this affection: psychogenic, organic or toxic.
      Neuroletic malignant syndrome is a potentially fatal complication of neuroleptic
      treatment occuring in about 1% of patients treated with neuroleptic. This
      syndrome is characterised by consciousness alteration, extrapyramidal symptoms,
      autonomic and thermic disorders. Similar clinical and biological features in
      catatonia and neuroleptic malignant syndrome (NMS) suggest a relationship between
      both affections and common physiopathological mechanisms and neurochemical basis:
      a central dopamine deficiency. We believe like many authors that catatonia and
      NMS are two aspects of a same disease, arising the question of chronology of both
      affections: NMS precipitates catatonia evolution. In the same way, Revuelta
      reported a case of patient who presented a lethal catatonia worsened by
      neuroleptic malignant syndrome. Neuroleptic malignant syndrome may be related to
      a dopamine deficiency, predominantly in the basal ganglia and anterior
      hypothalamus. Dopaminergic impairment has also been postulated to explain
      hyperthermia and catatonic signs in acute catatonie. ECT increases cerebral
      concentrations of dopamine, GABA and noradrelanine. The efficacy of ECT also
      argues for the dopaminergic hypothesis. A relation between those syndromes are
      complexes. A catatonic syndrome is regard as an acute form of malignant syndrome.
      In the other way, a severity scores of malignant syndrome are correlated among
      catatonic signs. In this case report, we suggest that the neuroleptic malignant
      syndrome accelerate the evolution to catatonic syndrome.

PMID- 16462703
TI  - The role of the Thalassaemia International Federation in health professionals'
      education.
AB  - The Thalassaemia International Federation (TIF) was established in 1986. The
      Federation has two important objectives: 1. To promote the continued control of
      thalassaemia major in countries with existing policies aimed at control, and 2.
      To support the establishment of policies of control in every affected country of
      the world. Over the years TIF has: - Held workshops and seminars attended by over
      7,000 from 35 countries - Organized 11 International Conferences attended by
      5,150 from 62 countries - Organized field trips/delegation visits in 42 countries
      - Prepared, published and distributed 70,000 books to 96 countries - Trained
      physicians and scientists from medical centres in the UK, US, Italy, Greece and
      Cyprus - Initiated and co-ordinated projects and clinical studies overseen by
      international experts in over 50 countries. - Established a vast network of
      scientific collaborators from every corner of the world, and - Has promoted close
      and productive collaborations with major health organizations. One of the most
      important projects that TIF has conducted was a multi-centre study on endocrine
      complications in the different affected regions of the world. It is hopeful that
      through the analysis of data already obtained and expected, other projects
      related to blood transfusion therapy, iron chelation and chronic hepatitis could
      be organized.

PMID- 16462704
TI  - Iron and the liver.
AB  - Iron is an important bio-catalyst of oxidation-reduction reactions in the cell
      and is essential for life. Paradoxically, it may also be lethal when the fraction
      of redox-active metal ions exceeds that sequestered in specialized proteins or
      cellular compartments, and uncontrolled production of free radical species may
      arise. The liver is the main body site for iron stores and central in the
      regulation of iron homeostasis. Important iron-proteins, such as hepcidin, the
      iron regulatory hormone, are specifically produced by the liver. Pathogenic
      mutations in hepatic iron transporters and regulators lead to hereditary iron
      overload diseases, including hemochromatosis. Iron toxicity depends on its
      excessive accumulation and is due to promotion of oxidant stress: free radicals
      and membrane oxidation by-products cause hepatocellular death by triggering
      organelle dysfunction, or by activating cells involved in hepatic inflammation
      and fibrogenesis, such as Kupffer cells and hepatic stellate cells. Xenobiotics
      and hepatotoxins as well as immunological and host defense mechanisms may cause
      subtle changes in the pool of redox-active metal ions and in metal
      compartmentalization that potentially contribute to hepatotoxic, inflammatory and
      fibrogenic events. The hepatotoxic and profibrogenic potential of metal ions,
      particularly iron, is dramatic at moderate levels of tissue metal overload in
      concomitance with other inciting insults, such as alcohol abuse and viral
      hepatitis. Removal of metal excess from the liver in iron overload diseases is
      beneficial and prevents progression toward cirrhosis. The development of drugs
      able to block catalytically active metals, particularly iron, may prove effective
      in other chronic liver diseases in which inflammatory, degenerative and
      fibrogenic processes are fueled by redox-active metal ions.

PMID- 16462705
TI  - Prevalence of endocrine complications and short stature in patients with
      thalassaemia major: a multicenter study by the Thalassaemia International
      Federation (TIF).
AB  - Although numerous studies are available in the literature on endocrine
      complications in thalassaemia, little is known about this subject in developing
      countries. Therefore, an international multicenter study was conducted in a large
      series of children and adolescents with beta thalassaemia major in order to
      obtain more information on the prevalence of short stature and endocrine
      complications in different areas of the world and to elucidate the problems that
      must be dealt with in the future. A questionnaire was sent to 29 Centres treating
      a total of 3817 beta thalassaemia major patients. Thirty-six per cent of patients
      were over the age of 16 years. Short stature was present in 31.1% of males and
      30.5% of females, and the prevalence of growth hormone deficiency was 7.9% in
      males and 8.8% in females. Lack of pubertal changes was the most common endocrine
      complication (40.5%) followed by hypoparathyroidism (6.9%), impaired glucose
      tolerance (6.5%), insulin-dependent diabetes mellitus (3.2%) and primary
      hypothyroidism (3.2%). The prevalence of endocrine complications differed among
      centres, particularly for growth hormone deficiency, hypoparathyroidism and
      hypothyroidism. Compliance to chelation therapy was poor in 51% of patients and
      serum liver enzymes were high in 65% of patients. Since several endocrine glands
      may be affected in patients with thalassaemia major, and their life expectancy is
      now much longer, it is important that physicians be aware of the endocrine
      abnormalities that may develop. Therefore, periodic evaluation of these problems
      should be carried out in thalassaemic patients with iron overload, particularly
      after the age of 11 years. In conclusion, since iron overload and liver damage
      seem to be the most important factors responsible for endocrine complications,
      adequate compliance to chelation therapy and rigid precautions against liver
      infections are imperative.

PMID- 16462706
TI  - Reduced insulin growth factor I concentrations in iron-overloaded beta
      thalassaemic patients with normal growth hormone secretion and liver function.
AB  - We selected 92 subjects (46 females and 46 males), aged 10-15 years, from the
      Haematology and Endocrine Clinic of Shiraz University, Iran. Forty-six were beta
      thalassaemia patients (beta-Th) with short stature, 23 had idiopathic short
      stature (ISS) and 23 were healthy children with a standing height between the
      10th and 95th percentile. Growth hormone (GH) secretion was normal in 23 beta-Th
      patients and reduced in the remaining 23 patients. A low insulin growth factor I
      (IGF-I) was found in 73.9% of beta-Th patients with GH deficiency, 56.5% of beta
      Th patients with normal GH secretion to stimulation test and 8.7% of children
      with ISS. The reduced IGF-I concentration in beta-Th patients with normal GH
      secretion may be explained by partial insensitivity to GH (GHIS), neurosecretory
      dysfunction, low bioactive GH or increased proportion of circulating, non-22-kDa
      GH isoform. The possibility of GHIS in beta-Th patients with short stature
      indicates that higher doses of rechGH may be required to obtain an improvement in
      growth velocity in beta-Th patients.

PMID- 16462708
TI  - Effects of acarbose in patients with beta-thalassaemia major and abnormal glucose
      homeostasis.
AB  - Seventeen TM patients with impaired glucose tolerance (IGT) or non-insulin
      dependent diabetes mellitus (NIDDM) and hyperinsulinism were treated for 12
      months with acarbose (100 mg. orally with breakfast, lunch and evening meals). An
      improvement in glucose tolerance was observed in 2 out of 11 TM patients with IGT
      and in all TM patients with NIDDM. Acarbose does not appear to directly improve
      insulin resistance but may have an indirect effect delaying the absorption of
      glucose of complex carbohydrates and disaccharides. It may be concluded that
      acarbose may represent a useful first-line therapy for improving glycemic control
      in TM patients with abnormalities of glucose homeostasis and hyperinsulinism.

PMID- 16462707
TI  - HCV and HGV infection, iron overload and liver disease in multitransfused
      patients with thalassaemia and persistently normal or abnormal transaminase
      levels.
AB  - Prevalence and influence on liver disease of HCV and HGV infections, and HCV
      genotypes were studied in 28 HCV-Ab positive multitransfused thalassaemia
      patients with persistently normal ALT levels (group A) matched by sex and age
      with 28 patients with increased ALT levels (group B). Laboratory and virologic
      tests (all patients), liver biopsy (28 patients) and LIC by SQUID (30 patients)
      were performed. In group A, HCV-RNA was positive in 39%, genotype 2a was detected
      in 91%. In Group B, HCV-RNA was positive in 89%, prevalence of genotype 1b and 2a
      was 52% and 48% respectively; compared with group A, they had significantly
      increased values of gammaGT, AF, BA, TP, IgG, IgA, LIC (group B: 2,142 -/+ 1,524
      microg/g liver; group A: 1,084 -/+ 610 microg/g liver). Overall prevalence of HGV
      RNA was low (12.5%) and not significantly different between groups. Liver
      biopsies revealed no cirrhosis and severe fibrosis was found in 3 HCV viremic
      patients in group B. In 14 viremic patients examined both for LIC and liver
      histology, mild fibrosis was observed in 71%, in which iron overload was below 5
      times the normal value. In conclusion, in patients with normal ALT levels, active
      HCV infection must be excluded by evaluation of HCV-RNA. Liver biopsy is
      indicated in HCV viremic patients, independent of ALT levels; in non-viremic
      patients, increased ALT levels may be due to iron overload and LIC measurement is
      indicated. Our data emphasise the crucial role of chelation therapy to maintain
      low LIC levels in order to prevent progression of fibrosis to cirrhosis in
      patients with HCV chronic hepatitis.

PMID- 16462709
TI  - Evolution of glucose intolerance and diabetes in transfused patients with
      thalassemia.
AB  - OBJECTIVE: To study the evolution of glucose disturbances (GD) in patients with
      thalassemia aged 11-30 years. DESIGN AND METHODS: A total of 263 patients,
      classified into three groups on the basis of age, and period of follow-up ranging
      from 2-10 years, were studied. Evolution of GD was assessed through serial oral
      glucose tolerance tests (OGTT), based on WHO criteria. RESULTS: At baseline (11
      14 years of age) evaluation of OGTT disclosed a prevalence of 16.3% of impaired
      glucose tolerance (IGT), and zero for diabetic tolerance (DT). Prevalence of IGT
      increased progressively up to 39% in the following 4 years, but remained constant
      during the last 6 years of observation. In contrast, DT had a very low
      prevalence, beginning with 0.5% at 13-16 years, increasing to 2.4% by the age of
      21-24 years. CONCLUSIONS: During puberty and early adolescence impaired glucose
      tolerance (IGT) was found in a considerable proportion of thalassemics. In
      contrast, DT was infrequent and progression to DM was slow. Only 12.4% of
      patients with IGT developed DT within a period of 10 years. Further studies are
      necessary to identify all of the factors contributing to abnormalities of glucose
      metabolism in thalassemic patients.

PMID- 16462711
TI  - Glucose metabolism disorders improvement in patients with thalassaemia major
      after 24-36 months of intensive chelation therapy.
AB  - Thalassaemic patients with haemocromatosis often present with metabolic
      disturbances such as diabetes mellitus. A group of adult thalassaemic patients
      who received intensive oral and subcutaneous chelation therapy
      (Defferiprone/Ferriprox and Desferioxamine/Desferal) for a period of 24-36 months
      was studied for the presence of glucose metabolism disturbances (GMD).
      Investigation of the prevalence of diabetes mellitus (DM) and impaired glucose
      tolerance (IGT) was carried out by yearly oral glucose tolerance tests (OGTT).
      Results showed that GMD (DM and IGT) improved in 1/3 of the patients after the
      intensive combined chelation treatment, a finding that we attributed to a
      reduction in liver iron deposits. Although this study is still in progress we
      believe that intensive combined chelation therapy may have a positive effect on
      glucose metabolism.

PMID- 16462710
TI  - Effects of acarbose in beta-thalassaemia major patients with normal glucose
      tolerance and hyperinsulinism.
AB  - The pathogenesis of diabetes in thalassaemia is complex and multifactorial.
      Understanding the sequence of abnormalities in the progression from normal
      glucose tolerance to impaired glucose tolerance may help in the formulation of
      ways to intervene in this process. In our study, we assessed the effects of
      acarbose, an alpha-glucosidase inhibitor, in five young adult thalassaemic
      patients with hyperinsulinism and normal oral glucose tolerance test (OGTT). A
      decrease of fasting insulin levels, insulin peak and area under the curve (AUC)
      after OGTT, were observed in thalassaemic patients receiving acarbose therapy.
      These values remained unchanged in an untreated group of eight thalassaemic
      patients. We believe that acarbose may have a potential role in the treatment of
      abnormalities of glucose homeostasis and insulin release.

PMID- 16462712
TI  - Prevalence of diabetes mellitus and impaired glucose tolerance in beta
      thalassemia patients with and without hepatitis C virus infection.
AB  - INTRODUCTION: Impaired glucose tolerance and diabetes are well known
      complications in beta-Thalassaemic multitransfused patients (beta-Th). Iron
      overload and chronic liver disease, viral infections and/or genetic factors may
      play an important role in the development of glucose intolerance. The present
      study aimed to investigate whether in beta-thalassemic patients the hepatitis C
      virus (HCV) infection may be an additional risk factor for the development of
      diabetes mellitus. PATIENTS AND METHODS: The study included 98 beta-Th
      multitransfused patients, 50 females and 48 males (mean age 15.9 -/+ 4 years;
      range: 8-32 years). Forty six (47%) patients were seropositive for HCV by ELISA.
      Six patients were diagnosed as diabetic before the present study. In the
      remaining oral glucose tolerance test was performed according to the
      recommendations of National Diabetes Data Group. Prevalence of diabetes and
      impaired glucose tolerance were compared in HCV-seropositive and HCV-seronegative
      groups. RESULTS: The prevalence of diabetes in HCV (+) adult beta-Th patients was
      higher compared to HCV (-) patients (15.2% vs. 1.9%, p: 0.02). No difference was
      observed in HCV-RNA (-) in the younger group of beta-Th patients. CONCLUSIONS:
      The prevalence of diabetes in adult thalassemic patients is significantly
      increased by HCV infection, but there is no difference between HCV(+) group and
      HCV(-) group in age range of 8-15 years. It is probable that the existence of
      hemosiderosis makes the effect of HCV infection on glucose metabolism clinically
      more evident.

PMID- 16462713
TI  - Diabetes mellitus and impaired glucose tolerance in thalassaemia major:
      incidence, prevalence, risk factors and survival in patients followed in the
      Ferrara Center.
AB  - Two hundred and seventy-three patients with thalassaemia major (TM) were followed
      in the Ferrara Thalassaemia Centre over a thirty-year period. Forty-two patients
      had insulin dependent diabetes mellitus (IDDM). The first case was diagnosed in
      1973. The incidence of IDDM peaked in 1986 (3.9%), and it was 0.7% at the time of
      the study (March 1998). The prevalence of IDDM increased progressively over time,
      reaching 14.2% in 1998. Mean age at diagnosis of IDDM was 18.2 -/+ 3.6 years and
      this also rose significantly during the study period (p<0.01). Hypogonadism was
      present in 91% of patients with IDDM, hypothyroidism in 68%, hypoparathyroidism
      in 21%, and cardiopathy in 69%, all significantly more prevalent than in patients
      without IDDM. These complications appeared with the same frequency before and
      after the diagnosis of IDDM. Survival of patients with and without IDDM was
      similar and no difference in the primary cause of death was found between the two
      groups. Main risk factors associated with IDDM were poor compliance with
      desferioxamine (DFO) treatment (p<0.05%), advanced age at the start of intensive
      chelation therapy (p<0.001), liver cirrhosis or severe fibrosis (p<0.0001, odds
      ratio 9.5, CI 95% 2.8-32.6). Prevalence of impaired glucose tolerance (IGT) was
      highest in 1981, 1984, and 1985 when the incidence of IDDM was increasing; in
      1995 the prevalence of IGT in patients aged 16-20 years was lower in comparison
      with that observed in 1975 (17% vs. 59%, p<0.01). Risk factors associated with
      IGT were: male sex (p<0.05), poor compliance with DFO therapy (p<0.05) and liver
      iron concentration 4 times above the normal value. In conclusion, our
      longitudinal study confirms that the incidence of IDDM and prevalence of IGT have
      been decreasing over the course of the last decade, appearing at a more advanced
      age, although some differences have not reached statistical significance. Iron
      overload and liver disease were the main associated risk factors, while positive
      family history for diabetes did not influence glucose metabolism in our patients.

PMID- 16462714
TI  - The impact of iron overload and genotype on gonadal function in women with
      thalassaemia major.
AB  - OBJECTIVE: The purpose of this study is to evaluate the impact of chronic iron
      overload and genotype on gonadal function in women with thalassaemia major.
      PATIENTS AND METHODS: The study population consists of 101 women aged 15-48 years
      who were treated between 1981 and 1999. These women were divided into two groups
      according to their genotype: [A=no modifying genetic factor and B=presence of
      modifying factors], and into four groups according to their menstrual history: NM
      (normal menstruation), OLM (oligomenorrhea), PA (primary amenorrhea), and SA
      (secondary amenorrhea). RESULTS: Women with NM maintained eumenorrhoea for 14.62
      years, whereas those with SA did so for 6.94 years. The serial values of both FSH
      and LH after stimulation with GnRH were lower in women with SA and PA (p<0.05)
      compared to women with OLM and NM. The average value of the minimum, mean and
      maximum ferritin levels over a period of 20 years displayed an increasing trend
      from women with NM to those with SA and PA. The lower levels of ferritin in women
      in Group A did not protect them from developing SA. In addition women with SA,
      who belong to Group A, had a shorter duration of eumenorrhoea compared to the
      ones with SA who belong to Group B. CONCLUSIONS: Although the pathogenesis of
      gonadal dysfunction in thalassaemia is known to be the consequence of iron
      overload, this study demonstrates that genotype acts as an independent variable,
      contributing to the development of SA in thalassaemic women.

PMID- 16462715
TI  - Update on fertility in thalassaemia major.
AB  - Therapeutic advances in thalassaemia major have significantly increased the
      average lifespan and improved the quality of life in thalassaemic patients.
      Therefore attainment of reproductive capacity and creation of a family has become
      a great task. Endocrine complications due to haemosiderosis and especially
      hypogonadotrophic hypogonadism are still present in a significant number of
      patients worldwide and often becomes a barrier in their desire for parenthood.
      The report of 358 successful pregnancies so far has provided strong evidence not
      only for the absence of any deleterious effect on the course of thalassaemia but
      also for the safety of the pregnancy in the thalassaemic woman. Ovarian function
      is well preserved in women suffering primary or secondary amenorrhea as they
      become able to conceive following a closely monitored stimulation therapy. The
      desire of the thalassaemic woman to become a mother is always viewed with special
      caution and sensitivity. Ambitions of this sort pose numerous medico legal and
      ethical issues that need to be addressed prudently if the patients' quality of
      life is to be optimized.

PMID- 16462716
TI  - The bone density of thalassemic patients of Boo Ali Sina Hospital, Sari, Iran in
      2002 does hydroxyurea help?
AB  - Osteopenia and osteoporosis are well known complications in beta thalassemia
      major (TM) patients. Their main cause is bone marrow hyperfunctioning.
      Hydroxyurea (HU) has recently been used successfully in TM to control ineffective
      erythropoiesis. This study was designed to measure the bone density of TM
      patients and evaluate whether the use of HU in these patients affects the
      development of osteoporosis. Sixty three patients with TM, 67% female, aged 25 
      /+ 7.2, were included in the study. Forty four percent were on HU and 56% had
      regular blood transfusions. Z-scores of the BD of femur and lumbar spine were 
      1.85 -/+ .78 and -1.61 -/+ 1.03 respectively and were the same in both sexes.
      Twenty two percent had normal BD, 45% were osteopenic, 17% had osteoporosis, and
      16% had severe osteoporosis. There was no statistically significant correlation
      between BD and age. In a case-control analysis, BDs of 16 patients taking HU for
      at least 2 years were compared to 16 patients matched by sex and age who did not
      use HU. The bone densities in each group were not statistically different.
      Osteopenia is common in our patients. As a more severe osteopenia was expected in
      patients who were not on blood transfusions, HU may have some beneficial effect.

PMID- 16462717
TI  - Bone density study at the distal radius, using pQCT analysis, in Greek
      thalassemic patients.
AB  - BACKGROUND: Expansion of marrow spaces in thalassemia patients contributes to
      reduced bone density and increased risk of fractures. Peripheral quantitative
      computed tomography (pQCT) measures the volumetric bone mineral density (vBMD)
      independently in different compartments. OBJECTIVE AND METHODS: To study the
      regional bone structure in thalassemia, we performed pQCT (XCT-2000 Scanner,
      Stratec Inc.) in 57 young adult patients with beta-thalassemia major, aged 21-44
      years (32 females). The vBMDs (total, trabecular, cortical + subcortical), Stress
      Strain Index (SSI) and the cross-sectional area (CSA) were determined at the "4%
      site" of the distal radius; data were compared to reference values. RESULTS:
      Total vBMD, trabecular, cortical plus subcortical vBMD in thalassemics were
      significantly lower than in healthy adults (p<0.005). Thalassemic males had
      significant higher values of vBMD, SSI and CSA than females (p<0.005).
      CONCLUSIONS: In Greek thalassemic patients a significant reduction in bone
      density, associated with increased morbidity and risk of fractures, has been
      detected on pQCT examination.

PMID- 16462718
TI  - Hypoparathyroidism and heart failure in thalassemic patients: a case report.
AB  - Hypocalcemic cardiomyopathy due to primary or secondary hypoparathyroidism is
      usually refractory to conventional treatment for cardiac failure but responds
      favorably to the restoration of normocalcemia. We report on a thalassemic patient
      with severe cardiac failure due to hypocalcemia. Cardiac echocardiography showed
      impaired biventricular performance and laboratory analyses revealed
      hypoparathyroidism due to hemosiderosis. Concomitant treatment for heart failure
      and calcium supplementation was initiated. Thereafter, clinical and laboratory
      improvement was achieved. In the literature of thalassemic disorders, this is the
      first case of heart failure associated with hypoparathyroidism in which the
      patient recovered significantly after the correction of hypocalcemia, providing
      strong evidence to support our hypothesis of hypocalcemic myocardiopathy.

PMID- 16462719
TI  - Ultrasound thyroid evaluation in thalassemic patients: correlation between the
      aspects of thyroidal stroma and function.
AB  - Hypothyroidism is one of the most common endocrine complications in thalassemic
      patients, usually appearing in the second decade of life related to iron
      overload. Ultrasonography is one of the techniques most frequently used to
      evaluate the volume and structure of the gland. The aim of the present work was
      to evaluate the possible correlation between thyroid function and its appearance
      on ultrasound in 45 thalassemic patients. We found reduced antero-posterior
      diameter of the thyroid in 12 patients (26.6%), reduced echogenicity of the
      glandular tissue in 24 patients (46.6%), and diffuse spotty echogenicity in 15
      patients (33.3%). In our opinion, these patterns may be useful to indicate the
      need for further diagnostic evaluation of thyroid function. Follow-up studies are
      necessary to confirm this hypothesis.

PMID- 16462720
TI  - Paraplegia due to spinal cord compression by extramedullary erythropoietic tissue
      in a thalassaemia intermedia patient with gynecomastia secondary to cirrhosis:
      successful treatment with hydroxyurea.
AB  - We report a 24 years old patient with thalassaemia intermedia and gynecomastia,
      complicated by paraplegia and urinary/fecal incontinence due to spinal cord
      compression by an extramedullary erythropoiesis (EE) mass, treated with long-term
      hydroxyurea (HU). Neurological improvement occurred during the first 6 weeks of
      HU therapy (1,000 mg/day) and magnetic resonance imaging showed a reduction in EE
      mass. HU dosage was reduced to 500 mg/day after 5 months, and treatment was
      discontinued after 25 months. Five months later there was a partial recurrence of
      neurological symptoms, which responded to radiotherapy. HU may have a role in the
      symptomatic treatment of spinal cord compression due to EE, particularly when
      radiotherapy is unavailable.

PMID- 16462721
TI  - Healing of leg ulcers with hydroxyurea in thalassaemia intermedia patients with
      associated endocrine complications.
AB  - We report a preliminary clinical experience in the use of hydroxyurea (HU) for
      the treatment of leg ulcers in thalassaemia intermedia patients with associated
      endocrine complications. We administered HU 1 g/day to 6 adult patients with
      thalassaemia intermedia for 90 days. We observed an improvement (3 patients) or
      healing (3 patients) of chronic leg ulcers. Recurrence was observed in the
      absence of maintenance therapy (2 patients). Two patients discontinued HU because
      of adverse effects (stomach pain and fever). No significant increase in total Hb
      or HbF levels occurred. In conclusion, HU appears suitable for the treatment of
      leg ulcers unresponsive to conventional treatment in patients with thalassaemia
      intermedia.

PMID- 16462723
TI  - Defects in cardiomyocyte function: role of beta-adrenergic receptor dysfunction.
AB  - Heart failure is a common clinical syndrome characterized by increased levels of
      circulating catecholamines and extensive abnormalities in the beta-adrenergic
      receptor (betaAR) system. Interestingly, whether dampening of betaAR signals is
      beneficial or detrimental for the failing cardiomyocyte is still controversial.
      In this review we will discuss a number of studies addressing the role of betaAR
      dysfunction in the development and progression of cardiomyocyte failure, and
      novel possible strategies to ameliorate cardiomyocyte contractility in heart
      failure through the normalization of betaAR signaling.

PMID- 16462722
TI  - Cardiac sarcomeric function, small G-protein signaling, and heart failure.
AB  - Molecular signaling that induces cardiac hypertrophy and dilated cardiomyopathy
      and the transition to decompensation is complex and poorly understood. Extrinsic
      hemodynamic stresses such as hypertension as well as intrinsic stresses such as
      genetic defects in sarcomeric proteins and cytoskeletal proteins trigger the
      process. Both stresses lead to similar outcomes of altered contractility and
      eventually heart failure. Activation of G-protein coupled receptors initiates
      cascades of signaling pathways, which promote cardiac hypertrophy by
      phosphorylation of transcriptional factors and changes in gene expression.
      Stimulation of these signaling molecules also activates a variety of kinases and
      phosphatases that induce altered phosphorylation of myofilament proteins. In this
      review, we focused on these functional effects of small G-protein, Ras and Rho,
      signaling pathways that reside within the cytoplasm downstream of membrane
      receptors and upstream of the transcriptional factors. It has been demonstrated
      that phosphorylation of myofilament proteins alter mechano-energetics of
      myofilament and contractile function of the heart. Therefore, understanding the
      role of low molecular weight G-proteins in both cardiac and vascular biology has
      become particularly important in view of the development of specific inhibitors
      of effectors of small G-proteins such as p38 MAP kinase and Rho-dependent kinase.

PMID- 16462724
TI  - Review of dilated cardiomyopathies. Dilated cardiomyopathies and altered
      prothrombotic state: a point of view of the literature.
AB  - Heart failure is an enormously important clinical problem that, if not faced, may
      overwhelm health care resources. Primary and secondary cardiomyopathies cause the
      majority of cases of clinical heart failure, which is thus better approached from
      the utility point of view of myocardial failure. Furthermore, the risk of
      thromboembolic complications presenting in such disease may be higher than in
      ischemic cardiomyopathy. Intracardiac thrombi and mural endocardial plaques (from
      the organization of thrombi) are present at necropsy in more than 50% of patients
      with dilated cardiomyopathy (DCM). Several studies have shown that systemic and
      pulmonary emboli are more frequent in patients with ventricular thrombi or
      plaques. Dilated cardiomyopathy has been associated with left ventricular
      thrombosis which leads to substantial morbidity and mortality as a site for
      peripheral emboli. There are some studies on patients with dilated cardiomyopathy
      showing altered hemostasis and platelet behavior despite sinus rhythm. Platelet
      activation, thrombin activation and fibrinolytic activity are increased in
      patients with DCM compared to normal subjects. However, these markers reflecting
      coagulation activation in patients with left ventricle thrombus are comparable to
      those in patients without thrombus in the left ventricle. The pathophysiology and
      clinical issues concerning the susceptibility to develop left ventricular (LV)
      thrombosis and its complications like cerebrovascular disease in patients with
      DCM are summarized and the most recent articles present in the medical literature
      are reviewed.

PMID- 16462725
TI  - Role of transforming growth factor-beta1/Smads in regulating vascular
      inflammation and atherogenesis.
AB  - Accumulating evidence supports the role of inflammation in the development of a
      variety of chronic vascular diseases such as atherosclerosis, transplantation
      arteriosclerosis, and restenosis after vascular mechanical injury. Thus,
      identification of mechanisms to control inflammation may provide novel
      therapeutic targets to limit such disease states. Transforming growth factor
      beta1 (TGF-beta1) is a pleiotropic growth factor with potent immunomodulating
      effects on cells important to atherosclerotic lesion formation including
      endothelial cells, vascular smooth muscle cells, macrophages, and T cells. The
      mechanisms responsible for the protective, anti-inflammatory effects of TGF-beta1
      have recently become elucidated. This review focuses on the emerging role of the
      downstream TGF-beta1 signaling mediators, termed Smads, as regulators of vascular
      inflammation. These findings are beginning to establish a mechanistic scaffold
      with which to understand the cell-type specific function of Smads in the
      development of chronic inflammatory vascular disease states.

PMID- 16462726
TI  - Does 18F-FDG PET/CT play a role in the differential diagnosis of parotid masses.
AB  - AIM: The aim of the present study was to assess the accuracy of an hybrid PET/CT
      scanner in the evaluation of newly diagnosed parotid masses, comparing the
      results with those reported in the literature with using PET scanners only.
      METHODS: The potential role of 18F-FDG PET/CT in distinguishing benign from
      malignant parotid masses in 14 consecutive patients was investigated. All
      patients were preoperatively evaluated by means of ultrasound (US), US-guided
      fine needle aspiration (FNA) cytology, computed tomography (CT) scan, magnetic
      resonance imaging (MRI) and 18F-FDG PET/CT. For To interpreting FDG PET findings,
      the right to left parotid (R/L) SUV max ratio was calculated in a group of 54
      patients without evidence of parotideal disease (mean+/-SD = 1+/-0.2; range = 0.8
      1.2); considering the R/L SUV max ratio, focal or diffuse uptakes <0.8 or >1.2
      were considered as potentially pathological. RESULTS: Imaging data were compared
      with surgical and histopathological findings. At FDG PET/CT, 9 false positive
      cases were found (8 Warthin's tumours, 1 pleomorphic adenoma), 1 false negative
      (acinar cell carcinoma), 4 true negative (1 Warthin's tumour, 1 pleomorphic
      adenoma, 1 lymph epithelial cyst, 1 parotid inflammation) whereas there was no
      case of true positive. The global accuracy of FGD PET/CT was rather low = at 29%.
      CONCLUSIONS: In agreement with other preliminary reports in which the FDG PET
      without CT fusion imaging was used, in our experience 18F-FDG PET/CT did not
      prove to play a significant role in differential diagnosis (benign vs malignant)
      of parotid masses. Further studies collecting larger groups of patients are
      needed to further elucidate this observation.

PMID- 16462727
TI  - How accurate is the culture of Helicobacter pylori in a clinical setting? An
      appraisal.
AB  - AIM: The trend towards increasing prevalence of Helicobacter pylori (H. pylori)
      antibiotic resistance may jeopardize the efficacy of most regimens. Culture of
      the bacterium, the useful method able to address therapy, is influenced by
      various factors. Thus, validation of the procedure is fundamental. Most studies
      have been carried out in microbiological settings, while only few have been
      conducted in clinical frames. We evaluated the accuracy of culture for detection
      of H. pylori in a clinical dedicated laboratory. METHODS: Forty-six patients (28
      females, 18 males, mean age 56+/-4.7 years) were included. Thirty experienced
      failure to H. pylori eradication after at least 3 courses of treatment. The
      control group included 16 subjects suffering from gastroesophageal reflux disease
      and negativity for H. pylori infection. Diagnostic strategy was based on
      histology, culture testing, serology and 13C-urea breath test. A patient was
      considered infected if 2 tests were positive. A commercial culture medium in
      microaerophilic atmosphere was utilized. RESULTS: Out of 30 positive specimens,
      culture correctly identified 29. In 1 case, no growth of micro-organisms
      occurred. In the control group, bacterial culture accurately identified all
      negative samples. One of them indicated growth but neither aspect nor
      confirmation tests identified H. pylori. Sensitivity was 96.7%, specificity 100%,
      and accuracy 97.8%. Positive and negative predictive values were 100% and 94.1%,
      respectively. CONCLUSIONS: Culture of H. pylori is a feasible method and provides
      a good level of diagnostic accuracy even in a clinical setting by following
      international guidelines combined with training of specialized personnel.

PMID- 16462728
TI  - Nosocomial fungal infection in intensive care units.

PMID- 16462729
TI  - Pannocytes: mesenchymal or bone marrow origin?

PMID- 16462730
TI  - Misdiagnosis of neurofibromatosis type 1 as Proteus syndrome.

PMID- 16462731
TI  - The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar
      spindle formation.
AB  - The CDK11 (cyclin-dependent kinase 11) gene has an internal ribosome entry site
      (IRES), allowing the expression of two protein kinases. The longer 110-kDa
      isoform is expressed at constant levels during the cell cycle and the shorter 58
      kDa isoform is expressed only during G2 and M phases. By means of RNA
      interference (RNAi), we show that the CDK11 gene is required for mitotic spindle
      formation. CDK11 RNAi leads to mitotic checkpoint activation. Mitotic cells are
      arrested with short or monopolar spindles. gamma-Tubulin as well as Plk1 and
      Aurora A protein kinase levels are greatly reduced at centrosomes, resulting in
      microtubule nucleation defects. We show that the mitotic CDK11(p58) isoform, but
      not the CDK11(p110) isoform, associates with mitotic centrosomes and rescues the
      phenotypes resulting from CDK11 RNAi. This work demonstrates for the first time
      the role of CDK11(p58) in centrosome maturation and bipolar spindle
      morphogenesis.

PMID- 16462732
TI  - Quantitative nuclear texture features analysis confirms WHO classification 2004
      for lung carcinomas.
AB  - The purpose of this study was to discriminate the main subsets of lung carcinomas
      of the WHO classification of 2004 by nuclear chromatin texture feature analysis.
      Our collective comprised 56 typical and 19 atypical carcinoids, 37 small-cell
      carcinomas, 15 large-cell neuroendocrine carcinomas, 42 adenocarcinomas, and 26
      squamous cell carcinomas. After Feulgen staining, cell nuclei were automatically
      measured using a high-resolution image analyser (CytoSavant Oncometrics,
      Vancouver, BC, Canada). Texture features describing the granularity and the
      compactness of the nuclear chromatin were extracted for calculation of
      classification rules, which allowed the discrimination of different tumor groups.
      By applying the classification rule that described the granularity of the nuclear
      chromatin (defined by four different parameters) small-cell and non-small-cell
      lung carcinoma could correctly be discriminated in 93%. No significant
      discrimination was possible between the different subtypes of large-cell
      carcinomas, including large-cell neuroendocrine carcinoma. When using compactness
      of chromatin (defined by four texture parameters) as a means of discrimination,
      carcinoids and non-small-cell lung carcinomas were correctly distinguished in
      92%. No significant discrimination between neuroendocrine tumors was achieved
      though. Our findings are in accordance with the new WHO classification of 2004:
      neuroendocrine tumors of the lung are now classified according only to their
      mitotic counts and presence of necrosis but not by their morphology; their
      discrimination by the means of nuclear image analysis is not sufficient and
      therefore not appropriate any longer.

PMID- 16462733
TI  - The NuRD component Mbd3 is required for pluripotency of embryonic stem cells.
AB  - Cells of early mammalian embryos have the potential to develop into any adult
      cell type, and are thus said to be pluripotent. Pluripotency is lost during
      embryogenesis as cells commit to specific developmental pathways. Although
      restriction of developmental potential is often associated with repression of
      inappropriate genetic programmes, the role of epigenetic silencing during early
      lineage commitment remains undefined. Here, we used mouse embryonic stem cells to
      study the function of epigenetic silencing in pluripotent cells. Embryonic stem
      cells lacking Mbd3 - a component of the nucleosome remodelling and histone
      deacetylation (NuRD) complex - were viable but failed to completely silence genes
      that are expressed before implantation of the embryo. Mbd3-deficient embryonic
      stem cells could be maintained in the absence of leukaemia inhibitory factor
      (LIF) and could initiate differentiation in embryoid bodies or chimeric embryos,
      but failed to commit to developmental lineages. Our findings define a role for
      epigenetic silencing in the cell-fate commitment of pluripotent cells.

PMID- 16462734
TI  - VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic
      brain.
AB  - Vascular endothelial growth factor C (VEGF-C) was first identified as a regulator
      of the vascular system, where it is required for the development of lymphatic
      vessels. Here we report actions of VEGF-C in the central nervous system. We
      detected the expression of the VEGF-C receptor VEGFR-3 in neural progenitor cells
      in Xenopus laevis and mouse embryos. In Xenopus tadpole VEGF-C knockdowns and in
      mice lacking Vegfc, the proliferation of neural progenitors expressing VEGFR-3
      was severely reduced, in the absence of intracerebral blood vessel defects. In
      addition, Vegfc-deficient mouse embryos showed a selective loss of
      oligodendrocyte precursor cells (OPCs) in the embryonic optic nerve. In vitro,
      VEGF-C stimulated the proliferation of OPCs expressing VEGFR-3 and nestin
      positive ventricular neural cells. VEGF-C thus has a new, evolutionary conserved
      function as a growth factor selectively required by neural progenitor cells
      expressing its receptor VEGFR-3.

PMID- 16462735
TI  - Altering expectancy dampens neural response to aversive taste in primary taste
      cortex.
AB  - The primary taste cortex consists of the insula and operculum. Previous work has
      indicated that neurons in the primary taste cortex respond solely to sensory
      input from taste receptors and lingual somatosensory receptors. Using functional
      magnetic resonance imaging, we show here that expectancy modulates these neural
      responses in humans. When subjects were led to believe that a highly aversive
      bitter taste would be less distasteful than it actually was, they reported it to
      be less aversive than when they had accurate information about the taste and,
      moreover, the primary taste cortex was less strongly activated. In addition, the
      activation of the right insula and operculum tracked online ratings of the
      aversiveness for each taste. Such expectancy-driven modulation of primary sensory
      cortex may affect perceptions of external events.

PMID- 16462736
TI  - A transient network of intrinsically bursting starburst cells underlies the
      generation of retinal waves.
AB  - Pharmacologically isolated starburst amacrine cells (SACs) in perinatal rabbit
      retinas spontaneously generated semiperiodic calcium spikes and long-lasting
      after-hyperpolarizations (AHPs), mediated by calcium-activated, cyclic AMP
      sensitive potassium currents. These AHPs, rather than a depletion of
      neurotransmitters (as was previously believed), produced the refractory period of
      spontaneous retinal waves and set the upper limit of the wave frequency. Each SAC
      received inputs from roughly 10-30 neighboring SACs during a wave. These inputs
      synchronized and reshaped the intrinsic bursts to produce network oscillations at
      a rhythm different from that of individual SACs. With maturation, the
      semiperiodic bursts in SACs disappeared, owing to reduced intrinsic excitability
      and increased network inhibition. Thus, retinal waves are generated by a
      transient and specific network of cell-autonomous oscillators synchronized by
      reciprocally excitatory connections.

PMID- 16462737
TI  - The representation of perceived angular size in human primary visual cortex.
AB  - Two objects that project the same visual angle on the retina can appear to occupy
      very different proportions of the visual field if they are perceived to be at
      different distances. What happens to the retinotopic map in primary visual cortex
      (V1) during the perception of these size illusions? Here we show, using
      functional magnetic resonance imaging (fMRI), that the retinotopic representation
      of an object changes in accordance with its perceived angular size. A distant
      object that appears to occupy a larger portion of the visual field activates a
      larger area in V1 than an object of equal angular size that is perceived to be
      closer and smaller. These results demonstrate that the retinal size of an object
      and the depth information in a scene are combined early in the human visual
      system.

PMID- 16462738
TI  - Constitutive sharing of recycling synaptic vesicles between presynaptic boutons.
AB  - The synaptic vesicle cycle is vital for sustained neurotransmitter release. It
      has been assumed that functional synaptic vesicles are replenished autonomously
      at individual presynaptic terminals. Here we tested this assumption by using FM
      dyes in combination with fluorescence recovery after photobleaching and
      correlative light and electron microscopy in cultured rat hippocampal neurons.
      After photobleaching, synapses acquired recently recycled FM dye-labeled vesicles
      originating from nonphotobleached synapses by a process requiring dynamic actin
      turnover. The imported vesicles entered the functional pool at their host
      synapses, as revealed by the exocytic release of the dye upon stimulation. FM1-43
      photoconversion and ultrastructural analysis confirmed the incorporation of
      imported vesicles into the presynaptic terminal, where they mixed with the native
      vesicle pools. Our results demonstrate that synaptic vesicle recycling is not
      confined to individual presynaptic terminals as is widely believed; rather, a
      substantial proportion of recycling vesicles are shared constitutively between
      boutons.

PMID- 16462739
TI  - Monocyte emigration from bone marrow during bacterial infection requires signals
      mediated by chemokine receptor CCR2.
AB  - Monocytes recruited to tissues mediate defense against microbes or contribute to
      inflammatory diseases. Regulation of the number of circulating monocytes thus has
      implications for disease pathogenesis. However, the mechanisms controlling
      monocyte emigration from the bone marrow niche where they are generated remain
      undefined. We demonstrate here that the chemokine receptor CCR2 was required for
      emigration of Ly6C(hi) monocytes from bone marrow. Ccr2(-/-) mice had fewer
      circulating Ly6C(hi) monocytes and, after infection with Listeria monocytogenes,
      accumulated activated monocytes in bone marrow. In blood, Ccr2(-/-) monocytes
      could traffic to sites of infection, demonstrating that CCR2 is not required for
      migration from the circulation into tissues. Thus, CCR2-mediated signals in bone
      marrow determine the frequency of Ly6C(hi) monocytes in the circulation.

PMID- 16462740
TI  - Forced crumpling of self-avoiding elastic sheets.
AB  - Thin elastic sheets are important materials across length scales ranging from
      mesoscopic (polymerized membranes, clay platelets, virus capsids) to macroscopic
      (paper, metal foils). The crumpling of such sheets by external forces is
      characterized by the formation of a complex pattern of folds. We have
      investigated the role of self-avoidance, the fact that the sheets cannot self
      intersect, for the crumpling process by large-scale computer simulations. At
      moderate compression, the force-compression relations of crumpled sheets for both
      self-avoiding and phantom sheets are found to obey universal power-law
      behaviours. However, self-avoiding sheets are much stiffer than phantom sheets
      and, for a given compression, develop many more folds. Moreover, self-avoidance
      is relevant already at very small volume fractions. The fold-length distribution
      for crumpled sheets is determined, and is found to be well-described by a log
      normal distribution. The stiffening owing to self-avoidance is reflected in the
      changing nature of the sheet-to-sheet contacts from line-like to two
      dimensionally extended with increasing compression.

PMID- 16462742
TI  - Morphogenesis in skin is governed by discrete sets of differentially expressed
      microRNAs.
AB  - During embryogenesis, multipotent progenitors within the single-layered surface
      epithelium differentiate to form the epidermis and its appendages. Here, we show
      that microRNAs (miRNAs) have an essential role in orchestrating these events. We
      cloned more than 100 miRNAs from skin and show that epidermis and hair follicles
      differentially express discrete miRNA families. To explore the functional
      significance of this finding, we conditionally targeted Dicer1 gene ablation in
      embryonic skin progenitors. Within the first week after loss of miRNA expression,
      cell fate specification and differentiation were not markedly impaired, and in
      the interfollicular epidermis, apoptosis was not markedly increased. Notably,
      however, developing hair germs evaginate rather than invaginate, thereby
      perturbing the epidermal organization. Here we characterize miRNAs in skin, the
      existence of which was hitherto unappreciated, and demonstrate their differential
      expression and importance in the morphogenesis of epithelial tissues within this
      vital organ.

PMID- 16462743
TI  - Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in
      humans.
AB  - Hydatidiform mole (HM) is an abnormal human pregnancy with no embryo and cystic
      degeneration of placental villi. We report five mutations in the maternal gene
      NALP7 in individuals with familial and recurrent HMs. NALP7 is a member of the
      CATERPILLER protein family involved in inflammation and apoptosis. NALP7 is the
      first maternal effect gene identified in humans and is also responsible for
      recurrent spontaneous abortions, stillbirths and intrauterine growth retardation.

PMID- 16462744
TI  - Polygenic control of Caenorhabditis elegans fat storage.
AB  - Tubby mice and individuals with Bardet-Biedl syndrome have defects in ciliated
      neuron function and obesity, suggesting an as-yet unknown metabolic signaling
      axis from ciliated neurons to fat storage tissues. Here we show coordinate
      regulation of Caenorhabditis elegans fat storage by orthologues of these genes
      acting in ciliated neurons and by a 3-ketoacyl-coA thiolase (encoded by kat-1)
      that acts in fat storage tissue. A genetic screen for markedly enhanced fat
      storage in tub-1 mutants led to the isolation only of kat-1 alleles, which impair
      fatty acid beta-oxidation. kat-1 acts in the intestine, the major C. elegans fat
      storage tissue, and is transcriptionally upregulated in animals with high fat
      storage. A genetic screen for synergistic increase in fat storage of a kat-1
      mutant identified bbs-1. bbs-1 acts in 15 ciliated neurons that are poised to
      sense external and internal nutrient levels, supporting a model in which bbs-1
      and tub-1 in ciliated neurons form part of an ancient, conserved neuroendocrine
      axis. This pathway also includes genes encoding intraflagellar transport proteins
      and cyclic nucleotide gated channels, demonstrating that C. elegans fat storage
      is under polygenic control.

PMID- 16462745
TI  - Identification of an imprinting control region affecting the expression of all
      transcripts in the Gnas cluster.
AB  - Genomic imprinting results in allele-specific silencing according to parental
      origin. Silencing is brought about by imprinting control regions (ICRs) that are
      differentially marked in gametogenesis. The group of imprinted transcripts in the
      mouse Gnas cluster (Nesp, Nespas, Gnasxl, Exon 1A and Gnas) provides a model for
      analyzing the mechanisms of imprint regulation. We previously identified an ICR
      that specifically regulates the tissue-specific imprinted expression of the Gnas
      gene. Here we identify a second ICR at the Gnas cluster. We show that a
      paternally derived targeted deletion of the germline differentially methylated
      region (DMR) associated with the antisense Nespas transcript unexpectedly affects
      both the expression of all transcripts in the cluster and methylation of two
      DMRs. Our results establish that the Nespas DMR is the principal ICR at the Gnas
      cluster and functions bidirectionally as a switch for modulating expression of
      the antagonistically acting genes Gnasxl and Gnas. Uniquely, the Nespas DMR acts
      on the downstream ICR at exon 1A to regulate tissue-specific imprinting of the
      Gnas gene.

PMID- 16462746
TI  - Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5.
AB  - Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal
      trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and
      contains an intrinsic ubiquitin ligase activity, all of which require an N
      terminal A20 zinc finger followed immediately by a helix. The structure of the N
      terminal portion of Rabex-5 bound to ubiquitin at 2.5-A resolution shows that
      Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type
      of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which binds
      with approximately 29-microM affinity to the canonical Ile44 hydrophobic patch on
      ubiquitin. The second is a diaromatic patch on the A20 zinc finger, which binds
      with approximately 22-microM affinity to a polar region centered on Asp58 of
      ubiquitin. The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase
      activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme.

PMID- 16462747
TI  - Crystal structure of the essential N-terminal domain of telomerase reverse
      transcriptase.
AB  - Telomerase, a ribonucleoprotein enzyme, adds telomeric DNA repeats to the ends of
      linear chromosomes. Here we report the first high-resolution structure of any
      portion of the telomerase reverse transcriptase, the telomerase essential N
      terminal (TEN) domain from Tetrahymena thermophila. The structure, which seems to
      represent a novel protein fold, shows phylogenetically conserved amino acid
      residues in a groove on its surface. These residues are crucial for telomerase
      catalytic activity, and several of them are required for sequence-specific
      binding of a single-stranded telomeric DNA primer. The positively charged C
      terminus, which becomes ordered upon interaction with other macromolecules, is
      involved in binding RNA in a non-sequence-specific manner. The TEN domain's
      ability to bind both RNA and telomeric DNA, coupled with the notably strong
      effects on activity upon mutagenesis of single surface residues, suggest how this
      domain contributes to telomerase catalysis.

PMID- 16462748
TI  - Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting.
AB  - Hrs has an essential role in sorting of monoubiquitinated receptors to
      multivesicular bodies for lysosomal degradation, through recognition of
      ubiquitinated receptors by its ubiquitin-interacting motif (UIM). Here, we
      present the structure of a complex of Hrs-UIM and ubiquitin at 1.7-A resolution.
      Hrs-UIM forms a single alpha-helix, which binds two ubiquitin molecules, one on
      either side. These two ubiquitin molecules are related by pseudo two-fold screw
      symmetry along the helical axis of the UIM, corresponding to a shift by two
      residues on the UIM helix. Both ubiquitin molecules interact with the UIM in the
      same manner, using the Ile44 surface, with equal binding affinities. Mutational
      experiments show that both binding sites of Hrs-UIM are required for efficient
      degradative protein sorting. Hrs-UIM belongs to a new subclass of double-sided
      UIMs, in contrast to its yeast homolog Vps27p, which has two tandem single-sided
      UIMs.

PMID- 16462750
TI  - Completing the uric acid degradation pathway through phylogenetic comparison of
      whole genomes.
AB  - Mammals that degrade uric acid are not affected by gout or urate kidney stones.
      It is not fully understood how they convert uric acid into the much more soluble
      allantoin. Until recently, it had long been thought that urate oxidase was the
      only enzyme responsible for this conversion. However, detailed studies of the
      mechanism and regiochemistry of urate oxidation have called this assumption into
      question, suggesting the existence of other distinct enzymatic activities.
      Through phylogenetic genome comparison, we identify here two genes that share
      with urate oxidase a common history of loss or gain events. We show that the two
      proteins encoded by mouse genes catalyze two consecutive steps following urate
      oxidation to 5-hydroxyisourate (HIU): hydrolysis of HIU to give 2-oxo-4-hydroxy-4
      carboxy-5-ureidoimidazoline (OHCU) and decarboxylation of OHCU to give S-(+)
      allantoin. Urate oxidation produces racemic allantoin on a time scale of hours,
      whereas the full enzymatic complement produces dextrorotatory allantoin on a time
      scale of seconds. The use of these enzymes in association with urate oxidase
      could improve the therapy of hyperuricemia.

PMID- 16462749
TI  - Mapping the interaction surface of linker histone H1(0) with the nucleosome of
      native chromatin in vivo.
AB  - H1 linker histones stabilize the nucleosome, limit nucleosome mobility and
      facilitate the condensation of metazoan chromatin. Here, we have combined
      systematic mutagenesis, measurement of in vivo binding by photobleaching
      microscopy, and structural modeling to determine the binding geometry of the
      globular domain of the H1(0) linker histone variant within the nucleosome in
      unperturbed, native chromatin in vivo. We demonstrate the existence of two
      distinct DNA-binding sites within the globular domain that are formed by spatial
      clustering of multiple residues. The globular domain is positioned via
      interaction of one binding site with the major groove near the nucleosome dyad.
      The second site interacts with linker DNA adjacent to the nucleosome core.
      Multiple residues bind cooperatively to form a highly specific chromatosome
      structure that provides a mechanism by which individual domains of linker
      histones interact to facilitate chromatin condensation.

PMID- 16462751
TI  - Analyzing the dynamic bacterial glycome with a lectin microarray approach.
AB  - Glycosylation of bacterial cell surfaces is emerging as a critical factor in
      symbiosis, pathogenesis, cell-cell interactions and immune evasion. The lack of
      high-throughput analytical tools to examine bacterial glycans has been a major
      obstacle to the field and has hindered closer examination of the dynamics of
      carbohydrate variation. We have recently developed a lectin microarray for the
      analysis of glycoproteins. Herein we present a rapid analytical system based on
      this technology for the examination of bacterial glycans. The glycosylation
      pattern observed distinguishes closely related Escherichia coli strains from one
      another, providing a facile means of fingerprinting bacteria. In addition,
      dynamic alterations in the carbohydrate coat of a pathogenic E. coli strain are
      readily observed. The fast evaluation of real-time alterations in surface
      carbohydrate epitopes allows examination of the dynamic role of bacterial sugars
      in response to external stimuli such as the immune system.

PMID- 16462752
TI  - Designer probiotics for prevention of enteric infections.
AB  - Many microbial pathogens, including those responsible for major enteric
      infections, exploit oligosaccharides that are displayed on the surface of host
      cells as receptors for toxins and adhesins. Blocking crucial ligand-receptor
      interactions is therefore a promising therapeutic strategy. One approach is to
      express molecular mimics of host receptors on the surface of harmless recombinant
      bacteria that can survive in the gut. These 'designer probiotics' bind bacterial
      toxins in the gut lumen with very high avidity, thereby preventing disease. This
      article discusses recent progress with this strategy.

PMID- 16462753
TI  - Prions and their lethal journey to the brain.
AB  - Prion diseases are neurodegenerative conditions that cause extensive damage to
      nerve cells within the brain and can be fatal. Some prion disease agents
      accumulate first in lymphoid tissues, as they make their journey from the site of
      infection, such as the gut, to the brain. Studies in mouse models have shown that
      this accumulation is obligatory for the efficient delivery of prions to the
      brain. Indeed, if the accumulation of prions in lymphoid tissues is blocked,
      disease susceptibility is reduced. Therefore, the identification of the cells and
      molecules that are involved in the delivery of prions to the brain might identify
      targets for therapeutic intervention. This review describes the current
      understanding of the mechanisms involved in the delivery of prions to the brain.

PMID- 16462754
TI  - Detection of catheter-related bloodstream infections by the Gram stain-acridine
      orange leukocyte cytospin test in hematopoietic stem cell transplant recipients.
AB  - In patients with central venous catheters (CVCs), catheter-related bloodstream
      infections (CRBI) are a prominent cause of morbidity, excess hospital costs, and
      in some cases mortality. The aim of this prospective study was to assess the
      validity of the Gram stain-acridine orange leukocyte cytospin (AOLC) test for the
      diagnosis of CRBI in hematopoietic stem cell transplant (HSCT) recipients with
      nontunnelled CVCs, using the differential-time-to-positivity (DTP)/clinical
      criteria as the criterion standard to define CRBIs. CVCs were externalized,
      nontunnelled, polyurethane double lumen catheters (Arrows, Readings, USA). All
      CVCs were placed in the subclavian vein by the infraclavicular approach, in the
      operating room. Catheters were inserted percutaneously, using the Seldinger
      technique. Study catheters were not exchanged over guidewires. Between May 2002
      and December 2004, a total of 245 consecutive patients were included. Twenty-six
      of the 245 patients (10.6%) had CRBI as determined by the DTP method. The Gram
      stain-AOLC was positive in only two patients (7.6%) with a CRBI. Our results
      suggest that the Gram stain-AOLC test is not useful for the diagnosis of catheter
      related bloodstream infection in HSCT recipients.2006.

PMID- 16462755
TI  - Preemptive diagnosis and treatment of Epstein-Barr virus-associated post
      transplant lymphoproliferative disorder after hematopoietic stem cell transplant:
      an approach in development.
AB  - Hematopoietic stem cell transplant (HSCT) recipients are at risk for Epstein-Barr
      virus (EBV)-associated, post transplant lymphoproliferative disorder (PTLD).
      Studies have suggested that early treatment may improve the outcome of patients
      with PTLD. Thus, significant attention has been focused on PCR-based approaches
      for preemptive (i.e., prior to clinical presentation) diagnosis. Reports from
      several transplant centers have demonstrated that HSCT recipients with PTLD
      generally have higher concentrations of EBV DNA in the peripheral blood than
      patients without PTLD. However, the PCR values of patients with PTLD typically
      span multiple orders of magnitude and overlap significantly with values from
      patients without PTLD. Thus, questions remain about the sensitivity and
      predictive value of these assays. Preemptive strategies using rituximab and/or
      EBV-specific cytotoxic T lymphocytes have been evaluated in patients with
      elevated EBV viral loads. We review the current literature, discuss our
      institutional experience and identify several areas of future research that could
      improve the diagnosis and treatment of this life-threatening disorder in HSCT
      recipients.

PMID- 16462756
TI  - Financial burden of national health insurance for treating patients with
      transfusion-dependent thalassemia in Taiwan.
AB  - The thalassemias are a heterogeneous group of inherited hypochromic anemias of
      varying severity. The mainstay of supportive treatment is regular blood
      transfusion accompanied by iron-chelating therapy. Hematopoietic stem cell
      transplantation (HSCT) provides an alternative option when curative therapy is
      considered. More than 400 patients in Taiwan have beta-thalassemia major or other
      transfusion-dependent thalassemias, and their treatment costs account for a
      considerable percentage of the National Health Insurance expenditure. In this
      report, we estimated the treatment costs of conventional therapy (regular blood
      transfusion accompanied by iron-chelating agents) and HSCT. The undiscounted
      medical cost of 20 years of follow-up (20 years from diagnosis) and the
      undiscounted total lifetime cost were NT$ 4 739 888 (NT$ means New Taiwan
      Dollars)/US$ 149 288 and NT$ 11 529 990/US$ 363 149, respectively, for patients
      undergoing conventional therapy, and NT$ 2 639 982/US$ 83 149 and NT$ 3 511
      172/US$ 110 588, respectively, for those undergoing successful HSCT. Comparisons
      of treatment costs and other parameters between these two modalities can add to
      the information base on which policy is made by health authorities or clinicians.

PMID- 16462757
TI  - Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation
      (RISCT) using antilymphocyte antibodies in patients with high-risk acute myeloid
      leukemia (AML).
AB  - Hemopoietic stem cell transplantation (SCT) with fully ablative conditioning is
      associated with an age-related increase in treatment-related mortality. It is
      therefore particularly unsuited to older individuals, who are most at risk of
      developing acute myeloid leukemia (AML). Reduced-intensity SCT (RISCT) may be of
      value in this group. We report 17 consecutive patients with high-risk AML whose
      median age was 58 years and who received stem cells from HLA-matched siblings
      (n=5), or alternative donors (n=12). We used lymphodepleting antibodies as a part
      of the reduced-intensity conditioning regimen to limit the risk of graft
      rejection and graft-versus-host disease (GVHD). All patients engrafted. One
      patient developed severe fatal GVHD, and two patients died of infection. At a
      median follow-up of 861 days (372-1957 days), seven patients are alive in
      remission, which includes two patients treated in relapse and five patients who
      lacked an MHC identical sibling donor. Both progression-free survival and overall
      survival are 40% (95% CI, 17-64%). Hence, RISCT using lymphodepleting antibodies
      may be of value for older patients with AML, even in those with active or high
      risk disease, and even if they lack an MHC-identical sibling donor.

PMID- 16462758
TI  - Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma.
AB  - The cell cycle inhibitor p21Waf1/Cip1 is among the most important mediators of
      the tumor suppressor p53. However, there is increasing evidence indicating that
      p21 could favor tumorigenesis in specific cell types. In particular, the absence
      of p21 delays the development of thymic lymphomas induced either by ataxia
      telangiectasia mutated deficiency or by ionizing irradiation. Here, we extend
      these observations to the context of p53-deficient mice. The absence of p21
      results in a significant extension of the lifespan of p53-null and p53
      haploinsufficient mice, and this effect can be attributed exclusively to a
      decrease in the incidence of spontaneous thymic lymphomas. Specifically, despite
      the occurrence of a variety of tumor types in the context of p53 deficiency, the
      only tumors that were significantly impaired by the absence of p21 were thymic
      lymphomas. Moreover, the absence of p21 also delays the incidence of radiation
      induced thymic lymphomas in p53-deficient mice. Interestingly, p21-deficient
      lymphomas have a higher apoptotic rate than p21-proficient lymphomas, and this
      could be on the basis of the delayed incidence of thymic lymphomas in the absence
      of p21. Together, our results indicate that p21 plays an oncogenic role
      restricted to thymic lymphomas that is mechanistically independent of p53 and
      associated to a lower tumor apoptotic rate.

PMID- 16462759
TI  - Inhibition of Bax activity is crucial for the antiapoptotic function of the human
      papillomavirus E6 oncoprotein.
AB  - Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer in humans.
      The antiapoptotic viral E6 gene has been identified as a key factor for
      maintaining the viability of HPV-positive cancer cells. Although E6 has the
      potential to modulate many apoptosis regulators, the crucial apoptotic pathway
      blocked by endogenous E6 in cervical cancer cells remained unknown. Using RNA
      interference (RNAi), here, we show that targeted inhibition of E6 expression in
      cervical cancer cells leads to the transcriptional stimulation of the PUMA
      promoter, in a p53-dependent manner. This is linked to the activation and
      translocation of Bax to the mitochondrial membrane, cytochrome c release into the
      cytosol, and activation of caspase-3, in a PUMA-dependent manner. Moreover,
      inhibition of Bax expression by RNAi efficiently reverts the apoptotic phenotype,
      which results from inhibition of E6 expression. Thus, interference with the
      p53/PUMA/Bax cascade is crucial for the antiapoptotic function of the viral E6
      oncogene in HPV-positive cancer cells.

PMID- 16462761
TI  - Modulation of cellular radiation responses by histone deacetylase inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors are emerging as a new class of targeted
      cancer chemotherapeutics. Several HDAC inhibitors are currently in clinical
      trials and promising anticancer effects at well-tolerated doses have been
      observed for both hematologic and solid cancers. HDAC inhibitors have been shown
      to induce cell-cycle and growth arrest, differentiation and in certain cases
      apoptosis in cell cultures and in vivo. However, it is known that these compounds
      induce varying responses in different cells and biological settings, and
      identifying their precise mechanisms of action is an area of great interest.
      Important findings are continually expanding our understanding of the cellular
      effects of HDAC inhibitors and recent studies will be briefly outlined in this
      review. In addition to their intrinsic anticancer properties, numerous studies
      have demonstrated that HDAC inhibitors can modulate cellular responses to other
      cytotoxic modalities including ionizing radiation, ultraviolet radiation and
      chemotherapeutic drugs. Hence, there is a growing interest in potential clinical
      use of HDAC inhibitors in combination with conventional cancer therapies. In this
      review, the interaction of HDAC inhibitors with other anticancer agents is
      discussed. The focus of the article is on the different mechanisms by which HDAC
      inhibitors enhance the sensitivity of cells to the effects of ionizing radiation.

PMID- 16462760
TI  - Identification of RASSF8 as a candidate lung tumor suppressor gene.
AB  - The RASSF8 gene, which maps close to the KRAS2 gene, contains a RAS-associated
      domain and encodes a protein that is evolutionarily conserved from fish to
      humans. Analysis of the RASSF8 transcript revealed a complex expression pattern
      of 5'-UTR mRNA isoforms in normal lung and in lung adenocarcinomas (ADCAs), with
      no apparent differences. However, RASSF8 gene transcript levels were
      approximately seven-fold-lower in lung ADCAs as compared to normal lung tissue.
      Expression of RASSF8 protein by transfected lung cancer cells led to inhibition
      of anchorage-independent growth in soft agar in A549 cells and reduction of
      clonogenic activity in NCI-H520 cells. These results raise the possibility
      protein encoded by RASSF8 is a novel tumor suppressor for lung cancer.

PMID- 16462762
TI  - The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the
      nucleus and associates with it in an active complex.
AB  - Localization of beta-catenin in the cell is a key determinant in its decision to
      function as a critical mediator of cell adhesion at the surface or a
      transcription activator in the nucleus. SYT-SSX2 is the fusion product of the
      chromosomal translocation, t(X;18)(p11.2;q11.2), which occurs in synovial
      sarcoma, a soft tissue tumor. SYT-SSX2 is known to associate with chromatin
      remodeling complexes and is proposed to be involved in controlling gene
      expression. We report that SYT-SSX2 plays a direct role in beta-catenin
      regulation. When expressed in mammalian cells, SYT-SSX2-induced beta-catenin
      recruitment to the nucleus. Interestingly, known target genes of canonical Wnt
      were not activated as a result of SYT-SSX2 expression, nor was the nuclear
      localization of beta-catenin due to one of the signaling pathways normally
      implicated in this event. beta-Catenin accumulation in the nucleus led to the
      formation of a transcriptionally active nuclear complex that contained SYT-SSX2
      and beta-catenin. More importantly, depletion of SYT-SSX2 in primary synovial
      sarcoma cells resulted in loss of nuclear beta-catenin signal and a significant
      decrease in its signaling activity. These results unravel a novel pathway in the
      control of beta-catenin cellular transport and strongly suggest that SYT-SSX2
      contributes to tumor development, in part through beta-catenin signaling.

PMID- 16462763
TI  - Identification of vitamin D receptor as a target of p63.
AB  - p63, a p53 homolog has been shown to play a role in development and cancer. p63
      is essential for both commitment of ectoderm to stratified epithelia and for the
      proliferative potential of epithelial stem cells. p63 knockout mice are born with
      severe development defects and lack organs of epithelial origin. In addition, p63
      has also been shown to play a role in cancer development through the differential
      regulation of genes with tumor suppressor function and genes involved in
      metastasis. In order to understand the role of p63 in cancer and development,
      genes that are specifically regulated by p63 but not p53 were identified. In this
      study, we provide evidence that p63gamma specifically upregulates vitamin D
      Receptor (VDR). In contrast, p53 does not appear to be involved in upregulation
      of VDR expression. Additionally, we demonstrate that a naturally occurring p63
      missense mutant, p63gamma (R279H) and p14(ARF), both act in a dominant negative
      manner to inhibit p63gamma-mediated upregulation of VDR. Furthermore, using
      chromatin immunoprecipitation assays, we demonstrated that p63 directly binds to
      the VDR promoter in vivo. Our findings clearly demonstrate that VDR is a direct
      target of p63 and suggests that p63 may play a role in cancer and differentiation
      through modulation of the VDR pathway.

PMID- 16462764
TI  - Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species
      (ROS).
AB  - Overexpression of the c-Met/hepatocyte growth factor receptor(HGF-R) proto
      oncogene and abnormal generation of intracellular oxygen species (reactive oxygen
      species (ROS)) have been linked, by independent lines of evidence, to cell
      transformation and to malignant growth. By comparing two subpopulations of the
      B16 mouse melanoma (B16-F0 and B16-F10) endowed with different lung metastasis
      capacities (low and high, respectively) we found that both the
      expression/phosphorylation of c-Met and the steady-state levels of ROS positively
      correlated with metastatic growth. shRNA-mediated downregulation of c-Met in F10
      cells led to a parallel decrease in the generation of oxygen species and in
      metastatic capacity, suggesting that oxidants may mediate the pro-metastatic
      activity of the HGF receptor. c-Met activation by a ligand elicits the formation
      of oxidant species through the oxidase-coupled small GTPase Rac-1, a relevant
      downstream target of the HGF-R. Moreover, cell treatment with the catalytic ROS
      scavengers EUK-134 and EUK-189 attenuates Met signaling to ERKs and inhibits the
      anchorage-independent growth of F10 cells, consistent with a critical role for
      oxygen species in HGF signaling and in aggressive cell behavior. Finally, genetic
      manipulation of the Rac-ROS cascade at different levels demonstrated its crucial
      role in the pro-metastatic activity of c-Met in vivo. Thus, we have outlined a
      novel cascade triggered by c-Met and mediated by ROS, linked to metastasis and
      potentially targetable by new antimetastatic, redox-based therapies.

PMID- 16462765
TI  - Trp53-dependent DNA-repair is affected by the codon 72 polymorphism.
AB  - Trp53 is arguably the most critical tumour suppressor gene product that inhibits
      malignant transformation. Besides mutations that inactivate Trp53 functions,
      genetic polymorphisms have been suggested to be risk factors for cancer. A
      polymorphic site at codon 72 in exon 4 encodes either an arginine amino acid
      (Trp53(72R)) or a proline residue (Trp53(72P)). Previous studies have shown that
      the Trp53(72R) form is more efficient in apoptosis induction, whereas the
      Trp53(72P) form was suggested to induce G1 arrest better. Here we report that
      Trp53(72P) is more efficient than Trp53(72R) in specifically activating several
      Trp53-dependent DNA-repair target genes in several cellular systems. Moreover,
      using isogenic cell lines and several DNA-repair assays, we show that Trp53(72P)
      cells have a significantly higher DNA-repair capacity than the Trp53(72R) cells.
      Furthermore, Trp53(72P)-expressing cells exhibit reduced micronuclei formation
      compared to Trp53(72R)-expressing cells, suggesting that genomic instability is
      reduced in these cells. Together, the data highlight the functional differences
      between the Trp53 polymorphic variants, and suggest that their expression status
      may influence cancer risk.

PMID- 16462766
TI  - Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol
      mediated cell death via PI3K/AKT.
AB  - In hematopoietic cells the transforming potential of the ecotropic viral
      integration site 1 (Evi1) oncogene is thought to be dependent upon the ability to
      inhibit TGFbeta signaling. Although Evi1 has recently been implicated in certain
      epithelial cancers, the effects of Evi1 on transformation and TGFbeta signaling
      in epithelial cells are not completely understood. Herein, we have determined the
      effects of Evi1 on TGFbeta signaling in intestinal epithelial cells. Stable
      expression of Evi1 in non-transformed intestinal epithelial cells inhibited
      induction of some Smad3-dependent TGFbeta target genes, such as PAI1. However,
      TGFbeta-mediated induction of cellular adhesion signaling components such as
      integrin1 and paxillin was not inhibited by Evi1; nor did Evi1 inhibit TGFbeta
      mediated epithelial to mesenchymal transition. Likewise, Evi1 did not inhibit
      TGFbeta-mediated downregulation of cyclin D1 or block TGFbeta-mediated growth
      inhibition. However, Evi1 did inhibit TGFbeta-mediated apoptosis by a process
      that involves phosphoinositide-3-kinase (PI3K) and its downstream effector AKT.
      The ability of Evi1 to suppress apoptosis is not restricted to TGFbeta-mediated
      cell death, since Evi1 also protects intestinal epithelial cells from taxol
      mediated apoptosis. Evi1 is overexpressed in some human colon cancer cell lines,
      and overexpression is associated with amplification of the Evi1 gene. Knockdown
      of Evi1 by siRNA inhibited AKT phosphorylation in HT-29 human colon cancer cells
      and increased their sensitivity to taxol-mediated apoptosis. These data indicate
      that Evi1 functions as a survival gene in intestinal epithelial cells and colon
      cancer cells, activating PI3K/AKT and conveying resistance to both physiological
      and therapeutic apoptotic stimuli.

PMID- 16462767
TI  - Interferon-gamma induces regression of epithelial cell carcinoma: critical roles
      of IRF-1 and ICSBP transcription factors.
AB  - We have developed an epithelial cell carcinoma model for studying efficacy of
      IFNgamma gene therapy and have identified components of IFNgamma-signaling
      pathway responsible for its direct anti-tumor actions. The tumor results from
      ectopic expression of SV40 Large T-Antigen (SV40 T-Ag) oncogene in lens of
      transgenic mouse (alphaT3) and complete regression of the tumor is induced by
      targeting expression of IFNgamma into malignant lens cells. Inflammatory cells
      are absent in lens of alphaT3 or DT (co-expressing IFNgamma and SV40-T-Antigen)
      mice and the transformed lens cells are non-immunogenic, suggesting non
      involvement of immunologic cells. We show that IFNgamma has direct growth
      inhibitory effects on tumor cells, induces death of tumor cells by apoptosis and
      that these effects are mediated by two transcription factors, IRF-1 (interferon
      regulatory factor-1) and ICSBP (interferon-consensus sequence-binding protein)
      induced by IFNgamma. Furthermore, stable transfection with ICSBP or IRF-1
      construct inhibits lens carcinoma cell growth by upregulating Caspase-1,
      p21(WAF1) and p27 expression. In contrast, tumor progression in alphaT3 lens
      correlates with inhibition of IRF-1 and ICSBP expression. Our results suggest
      that IFNgamma gene therapy maybe effective in malignant diseases for which DNA
      tumor viruses are etiologic agents and that antitumor actions of IRF-1/ICSBP can
      be exploited therapeutically to circumvent adverse clinical effects associated
      with IFN therapy.

PMID- 16462768
TI  - Mutually exclusive NRASQ61R and BRAFV600E mutations at the single-cell level in
      the same human melanoma.
AB  - Activating BRAF or NRAS mutations have been found in 80% of human sporadic
      melanomas, but only one of these genetic alterations could be detected in each
      tumour. This suggests that BRAF and NRAS 'double mutants' may not provide
      advantage for tumour growth, or may even be selected against during
      tumorigenesis. However, by applying mutant-allele-specific-amplification-PCR
      method to short-term melanoma lines, one out of 14 tumours was found to harbour
      both BRAFV600E and the activating NRASQ61R mutations. On the other hand, analysis
      of 21 melanoma clones isolated by growth in soft agar from this tumour indicated
      that 16/21 clones harboured a BRAFV600E, but were wild-type for NRAS, whereas the
      remaining had the opposite genotype (NRASQ61R/wild-type BRAF). When compared to
      BRAFV600E clones, NRASQ61R clones displayed reduced growth in soft agar, but
      higher proliferative ability in vitro in liquid medium and even in vivo after
      grafting into SCID/SCID mice. These data suggest that NRAS and BRAF activating
      mutations can coexist in the same melanoma, but are mutually exclusive at the
      single-cell level. Moreover, the presence of NRASQ61R or BRAFV600E is associated
      with distinct in vitro and in vivo growth properties of neoplastic cells.

PMID- 16462769
TI  - Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated
      cytotoxicity.
AB  - Photodynamic therapy is a promising antitumor treatment modality approved for the
      management of both early and advanced tumors. The mechanisms of its antitumor
      action include generation of singlet oxygen and reactive oxygen species that
      directly damage tumor cells and tumor vasculature. A number of mechanisms seem to
      be involved in the protective responses to PDT that include activation of
      transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic
      pathways. Elucidation of these mechanisms might result in the design of more
      effective combination strategies to improve the antitumor efficacy of PDT. Using
      DNA microarray analysis to identify stress-related genes induced by Photofrin
      mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction
      of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection
      of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells
      to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an
      HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and
      human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon
      monoxide, direct products of HO-1 catalysed heme degradation, was responsible for
      cytoprotection. Importantly, desferrioxamine, a potent iron chelator
      significantly potentiated cytotoxic effects of PDT. Altogether our results
      indicate that HO-1 is involved in an important protective mechanism against PDT
      mediated phototoxicity and administration of HO-1 inhibitors might be an
      effective way to potentiate antitumor effectiveness of PDT.

PMID- 16462770
TI  - MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell
      lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy
      refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC
      represents a logical way forward in treating this tumor. Cisplatin, a commonly
      used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase
      (JNK) that, in turn, mediates induction of apoptosis. In analysing surgical
      tissue samples of NSCLC, we found that expression of MKP1/CL100, a negative
      regulator of JNK, showed a strong nuclear staining for tumor cells, whereas, in
      normal bronchial epithelia, MKP1 was localized in the cytoplasm as well as in
      nuclei. In the NSCLC-derived cell lines H-460 and H-23, we found that MKP1 was
      constitutively expressed. Expressing a small-interfering RNA (siRNA) vector for
      MKP1 in H-460 cells resulted in a more efficient activation by cisplatin of JNK
      and p38 than in the parental cells, and this correlated with a 10-fold increase
      in sensitivity to cisplatin. A similar response was also observed in H-460 and H
      23 cells when treated with the MKP1 expression inhibitor RO-31-8220. Moreover,
      expression of a siRNA-MKP2, an MKP1-related phosphatase, had no effect on H-460
      cell viability response to cisplatin. Tumors induced by H-460 cells expressing
      MKP1 siRNA grew slower in nu(-)/nu(-) mice and showed more susceptibility to
      cisplatin than parental cells, and resulted in an impaired growth of the tumor in
      mice. On the other hand, overexpression of MKP1 in the H-1299 NSCLC-derived cell
      line resulted in further resistance to cisplatin. Overall, the results showed
      that inhibition of MKP1 expression contributes to a slow down in cell growth in
      mice and an increase of cisplatin-induced cell death in NSCLC. As such, MKP1 can
      be an attractive target in sensitizing cells to cisplatin to increase the
      effectiveness of the drug in treating NSCLC.

PMID- 16462772
TI  - RORA, a large common fragile site gene, is involved in cellular stress response.
AB  - Common fragile sites (CFSs) are large genomic regions present in all individuals
      that are highly unstable and prone to breakage and rearrangement, especially in
      cancer cells with genomic instability. Eight of the 90 known CFSs have been
      precisely defined and five of these span genes that extend from 700 kb to over
      1.5 Mb of genomic sequence. Although these genes reside within some of the most
      unstable chromosomal regions in the human genome, they are highly conserved
      evolutionarily. These genes are targets for large chromosomal deletions and
      rearrangements in cancer and are frequently inactivated in multiple tumor types.
      There is also an association between these genes and cellular responses to
      stress. Based upon the association between large genes and CFSs, we began to
      systematically test other large genes derived from chromosomal regions that were
      known to contain a CFS. In this study, we demonstrate that the 730 kb retinoic
      acid receptor-related orphan receptor alpha (RORA) gene is derived from the
      middle of the FRA15A (15q22.2) CFS. Although this gene is expressed in normal
      breast, prostate and ovarian epithelium, it is frequently inactivated in cancers
      that arise from these organs. RORA was previously shown to be involved in the
      cellular response to hypoxia and here we demonstrate changes in the amount of
      RORA message produced in cells exposed to a variety of different cellular
      stresses. Our results demonstrate that RORA is another very large CFS gene that
      is inactivated in multiple tumors. In addition, RORA appears to play a critical
      role in responses to cellular stress, lending further support to the idea that
      the large CFS genes function as part of a highly conserved stress response
      network that is uniquely susceptible to genomic instability in cancer cells.

PMID- 16462771
TI  - The expression of antiapoptotic protein survivin is transcriptionally upregulated
      by DEC1 primarily through multiple sp1 binding sites in the proximal promoter.
AB  - Human differentially expressed in chondrocytes (DEC), mouse stimulated with
      retinoic acid and rat split and hairy related proteins constitute a structurally
      distinct class of the basic helix-loop-helix proteins. DEC1 is abundantly
      expressed in tumors and protects against apoptosis induced by serum starvation.
      In this study, we report that DEC1 antiapoptosis is achieved by inducing
      survivin, an antiapoptotic protein. In paired tumor-normal tissues, survivin and
      DEC1 exhibited a paralleled expression pattern. Tetracycline-induced expression
      of DEC1 in stable lines proportionally increased the expression of survivin. In
      reporter assays, DEC1 transactivated the survivin promoter but repressed the DEC2
      promoter. In contrast to the repression, the activation was delayed and varied
      depending on serum concentrations and cycle blockers. Studies with reporter
      mutants located, in the survivin promoter, two Sp1 sites that supported DEC1
      transactivation. Electrophoretic mobility shift assay and chromatin
      immunoprecipitation detected the presence of DEC1 in the survivin promoter. These
      findings establish that the survivin gene is a transcription target of DEC1, and
      induction of survivin is at least in part responsible for DEC1 antiapoptosis.

PMID- 16462778
TI  - School's out.

PMID- 16462773
TI  - BACH1 is a DNA repair protein supporting BRCA1 damage response.
AB  - The link between defects in BRCA1 and breast cancer development may be best
      understood by deciphering the role of associated proteins. BRCA1 associated C
      terminal helicase (BACH1) interacts directly with the BRCA1 C-terminal BRCT
      repeats, which are important for BRCA1 DNA repair and are mutated in the majority
      of BRCA1 familial cancers. Thus, BACH1 is a likely candidate for mediating BRCA1
      DNA repair and tumor suppression functions. Although previous evidence using
      overexpression of a dominant negative BACH1 has suggested that BACH1 is involved
      in BRCA1-DNA repair function, our results using BACH1 deficient cells provide
      direct evidence for involvement of BACH1 in DNA repair as well as for localizing
      BRCA1. Following DNA damage BACH1 is modified by phosphorylation, displays a
      BRCA1-like nuclear foci pattern and colocalizes with gamma-H2AX. Given that the
      BACH1/BRCA1 complex is unaltered by DNA damage and the intensity of BRCA1 foci is
      diminished in BACH1 deficient cells, BACH1 may serve to not only facilitate DNA
      repair, but also maintain BRCA1 in DNA damage foci.

PMID- 16462779
TI  - Earlier drug tests on people could be unsafe, critics warn.

PMID- 16462780
TI  - Side benefits sway developing nations to choose unneeded vaccines.

PMID- 16462781
TI  - New law offers drug makers sweeping protection against lawsuits.

PMID- 16462782
TI  - Powerful new database pins down emerging infections.

PMID- 16462783
TI  - New York's scheme to track diabetes stirs privacy concerns.

PMID- 16462784
TI  - Australia considers changing laws to allow therapeutic cloning.

PMID- 16462785
TI  - European scientists push spinal taps for Alzheimer diagnosis.

PMID- 16462787
TI  - Where the chips fall.

PMID- 16462789
TI  - Reply to 'Physician, heal thyself'.

PMID- 16462790
TI  - Reply to 'Physician, heal thyself'.

PMID- 16462791
TI  - Reply to 'Physician, heal thyself'.

PMID- 16462792
TI  - Reply to 'Physician, heal thyself'.

PMID- 16462794
TI  - Is it a DC, is it an NK? No, it's an IKDC.

PMID- 16462795
TI  - Oxygen deprivation provokes melanoma.

PMID- 16462796
TI  - Rich route for sugar.

PMID- 16462797
TI  - Malaria parasites up close.

PMID- 16462798
TI  - Angiogenesis and inflammation face off.

PMID- 16462800
TI  - Natural regulatory T cells control the development of atherosclerosis in mice.
AB  - Atherosclerosis is an immunoinflammatory disease elicited by accumulation of
      lipids in the artery wall and leads to myocardial infarction and stroke. Here, we
      show that naturally arising CD4(+)CD25(+) regulatory T cells, which actively
      maintain immunological tolerance to self and nonself antigens, are powerful
      inhibitors of atherosclerosis in several mouse models. These results provide new
      insights into the immunopathogenesis of atherosclerosis and could lead to new
      therapeutic approaches that involve immune modulation using regulatory T cells.

PMID- 16462801
TI  - A T-cell HCV vaccine eliciting effective immunity against heterologous virus
      challenge in chimpanzees.
AB  - Three percent of the world's population is chronically infected with the
      hepatitis C virus (HCV) and at risk of developing liver cancer. Effective
      cellular immune responses are deemed essential for spontaneous resolution of
      acute hepatitis C and long-term protection. Here we describe a new T-cell HCV
      genetic vaccine capable of protecting chimpanzees from acute hepatitis induced by
      challenge with heterologous virus. Suppression of acute viremia in vaccinated
      chimpanzees occurred as a result of massive expansion of peripheral and
      intrahepatic HCV-specific CD8(+) T lymphocytes that cross-reacted with vaccine
      and virus epitopes. These findings show that it is possible to elicit effective
      immunity against heterologous HCV strains by stimulating only the cellular arm of
      the immune system, and suggest a path for new immunotherapy against highly
      variable human pathogens like HCV, HIV or malaria, which can evade humoral
      responses.

PMID- 16462802
TI  - Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role
      in the induction of inflammation.
AB  - The angiopoietins Ang-1 and Ang-2 have been identified as ligands of the receptor
      tyrosine kinase Tie-2 (refs. 1,2). Paracrine Ang-1-mediated activation of Tie-2
      acts as a regulator of vessel maturation and vascular quiescence. In turn, the
      antagonistic ligand Ang-2 acts by an autocrine mechanism and is stored in
      endothelial Weibel-Palade bodies from where it can be rapidly released upon
      stimulation. The rapid release of Ang-2 implies functions of the angiopoietin-Tie
      system beyond its established role during vascular morphogenesis as a regulator
      of rapid vascular responses. Here we show that mice deficient in Ang-2 (encoded
      by the gene Angpt2) cannot elicit an inflammatory response in thioglycollate
      induced or Staphylococcus aureus-induced peritonitis, or in the dorsal skinfold
      chamber model. Recombinant Ang-2 restores the inflammation defect in Angpt2(-/-)
      mice. Intravital microscopy showed normal TNF-alpha-induced leukocyte rolling in
      the vasculature of Angpt2(-/-)mice, but rolling cells did not firmly adhere to
      activated endothelium. Cellular experiments showed that Ang-2 promotes adhesion
      by sensitizing endothelial cells toward TNF-alpha and modulating TNF-alpha
      induced expression of endothelial cell adhesion molecules. Together, these
      findings identify Ang-2 as an autocrine regulator of endothelial cell
      inflammatory responses. Ang-2 thereby acts as a switch of vascular responsiveness
      exerting a permissive role for the activities of proinflammatory cytokines.

PMID- 16462803
TI  - Design and use of conditional MHC class I ligands.
AB  - Major histocompatibility complex (MHC) class I molecules associate with a variety
      of peptide ligands during biosynthesis and present these ligands on the cell
      surface for recognition by cytotoxic T cells. We have designed conditional MHC
      ligands that form stable complexes with MHC molecules but degrade on command, by
      exposure to a defined photostimulus. 'Empty MHC molecules' generated in this
      manner can be loaded with arrays of peptide ligands to determine MHC binding
      properties and to monitor antigen-specific T-cell responses in a high-throughput
      manner. We document the value of this approach by identifying cytotoxic T-cell
      epitopes within the H5N1 influenza A/Vietnam/1194/04 genome.

PMID- 16462807
TI  - We're living in a 3D world.

PMID- 16462808
TI  - Flip-flopping membrane proteins.

PMID- 16462809
TI  - Promoter activation when the ChIPs are down.

PMID- 16462810
TI  - Translation, interrupted.

PMID- 16462811
TI  - Combing over heritable gene silencing.

PMID- 16462812
TI  - Helicase a go-go-go.

PMID- 16462814
TI  - Overview of the pharmacogenetics of HIV therapy.
AB  - The administration of standard doses of most antiretroviral drugs results in
      significant variations in plasma drug concentrations among different individuals,
      influencing antiviral activity as well as incidence of drug-related toxicities.
      The reasons for this large inter-individual variability in drug levels are
      multifactorial, and involve differences in metabolism related to gender,
      concomitant medications, drug compliance, underlying diseases and genetic
      factors. Pharmacogenetics is the discipline that analyses the genetic basis for
      the inter-individual variation in the body disposition of drugs. One of its main
      goals is to give grounds to individualized treatment. The majority of
      pharmacogenetic traits so far have involved drug metabolism. This is the case for
      the inherited variation in the pharmacokinetics and pharmacodynamics of drugs
      such as hydralazine or isoniazid, which is due to polymorphisms in the N
      acetyltransferase-2 (NAT2) gene, which allows splitting the population into three
      categories: slow, intermediate, and fast metabolizers. Pharmacogenetic studies
      conducted so far with antiretroviral drugs have focussed on metabolizer enzymes
      at the liver and on transporter proteins on cell membranes. Herein, we review the
      most relevant metabolizer enzymes and protein transporters, along with the
      genetic polymorphisms, which seem to influence the pharmacokinetics of
      antiretroviral drugs, ultimately determining its efficacy and toxicity.

PMID- 16462815
TI  - Haloperidol induces apoptosis via the sigma2 receptor system and Bcl-XS.
AB  - Toxicity of the typical antipsychotic haloperidol (HAL) comprises an apoptotic
      component that we link to pro-apoptotic Bcl-XS in PC12 preneuronal and N2a
      neuroblastoma cells. The mitochondrial translocation of Bcl-XS and its
      interaction with the pore-forming voltage-dependent anion channel (VDAC)
      correlates with the redistribution of cytochrome c and the cleavage of Poly(ADP
      ribose) polymerase. Haloperidol-induced apoptosis is mediated by the sigma2
      (sigma2) receptor system and does not involve the expected antagonism of the
      dopamine D(2) receptor, nor is it influenced by Vitamin E- or p53/Bax-mediated
      events. Pathological relevance is demonstrated by the cytotoxic synergism between
      HAL and the Alzheimer disease-related peptide beta-amyloid(1-40), which
      correlates with Bcl-XS expression and its interaction with VDAC, and with
      cytosolic cytochrome c translocation. These data provide for a unique apoptotic
      mechanism that could underscore the clinical risks associated with HAL,
      particularly following chronic regimens or in the elderly.

PMID- 16462816
TI  - Genetics of suicide.
AB  - The concept that genetic factors contribute to the complex trait of suicidal
      behaviour has stimulated much work aimed at identifying susceptibility genes. So
      far molecular genetic studies focused on the serotonergic pathway as the intent
      to die and the lethality of suicide acts were related to the serotonergic system.
      Two genes have so far emerged as being involved in the vulnerability for
      suicidality: first, the intronic polymorphisms (A218C or A779C) of the tryptophan
      hydroxylase 1 (TPH1) gene, which was suggested as a quantitative risk factor for
      suicidal behaviour; second, the insertion/deletion polymorphism of the serotonin
      transporter gene (5-HTTLPR), which does not seem to be involved in general
      suicidal behaviour, but in violent and repeated suicide attempts. The data have
      further shown that the MAOA gene, which is consistently associated with impulsive
      aggressive personality traits, is not related to suicide but might induce violent
      methods in subjects with other suicide risk factors. Predominantly negative were
      the findings with any type of the serotonin receptors and inconsistent with
      catecholamine-synthesizing and -metabolizing enzymes or with the dopaminergic
      receptors. This paper reviews the status of current knowledge in this area,
      points to the weakness of the investigations and presents new approaches beyond
      the serotonergic system.

PMID- 16462817
TI  - Total fat, fat distribution and blood pressure according to eating frequency in
      children living in southern Italy: the ARCA project.
AB  - The relationships between eating frequency and adiposity and cardiovascular risk
      factors have been poorly investigated in children. To evaluate this issue,
      anthropometric indices and blood pressure (BP) were measured in 3668 children,
      aged 6-11 years. Meals/snack frequency, assessed by a questionnaire, was 'Low' in
      332 (<or=3 meals/day), 'Intermediate' in 1334 (4/day) and 'High' in 2002
      (>or=5/day) children. Body mass index (BMI) and waist circumference significantly
      decreased going up across meals/snacks categories (BMI=20.5+/-0.2, 19.7+/-0.1 and
      18.8+/-0.1 kg/m2; waist=68.0+/-0.6, 66.6+/-0.3, 63.9+/-0.2 cm, for Low,
      Intermediate and High groups, respectively; M+/-s.e.; P<0.001 by ANCOVA trend
      analysis adjusted by age, sex, birth weight, physical activity, parental
      overweight and education level). BP decreased from Low to High group but
      differences were no longer significant after adjustment for BMI. In our sample of
      school children, the daily eating frequency was inversely associated with the
      degree of both total adiposity and central fat deposition.

PMID- 16462818
TI  - Influences of fat restriction and lipase inhibition on gastric emptying in
      obesity.
AB  - OBJECTIVE: Accelerated gastric emptying of solids may play a role in the
      pathogenesis of obesity. Orlistat, a potent lipase inhibitor, induces fat
      malabsorption and body weight loss but might accelerate gastric emptying as a
      result of suppressed CCK release. The aim was to investigate the role of fat
      restriction and lipase inhibition in CCK release and gastric emptying. SUBJECTS:
      A total of 28 patients (three male (M)/25 female (F); mean (s.d.) BMI 37.4(3.9)
      kg/m2) entering a randomized, double-blind, placebo-controlled study.
      MEASUREMENTS: CCK release and gastric emptying by scintigraphy at the start (T0),
      after 1 month of an energy- and fat-restricted diet and placebo (T1), and after 1
      month (T2) and 1 year (T3) of randomization to placebo or 120 mg orlistat three
      times a day. RESULTS: One month of dieting and a weight loss of 2.3 kg (2.1% of
      initial weight) did not affect gastric emptying of liquids and solids. Basal and
      meal-stimulated CCK levels remained unaltered. Placebo-treated subjects who
      continued the diet for 1 month demonstrated a borderline significant suppressed
      CCK secretion and a weight loss of 1.2 kg (1.0%) without an effect on gastric
      emptying. After 1 year, the CCK secretion recovered to or beyond values at the
      start. A significantly slower emptying of solids (17.6 (T3) versus 25.9 (T1)%/h)
      and a weight loss of 10.4 kg (9.9%) was observed. Subjects on 120 mg orlistat
      lost 2.5 kg (2.5%) after 1 month, and 9.8 kg (9.9%) after 1 year. Basal and
      postprandial CCK release decreased significantly after the first month of
      orlistat treatment but normalized after 1 year. Diet and lipase inhibition did
      not have any influence on gastric emptying. CONCLUSION: Energy and fat
      restriction of 1 month did not alter gastric emptying in the whole group.
      Continuation of the diet for 1 year resulted in a delayed gastric emptying of
      solids. Lipase inhibition did not result in a sustained depressed CCK release and
      the anticipated acceleration of gastric emptying did not occur.

PMID- 16462819
TI  - Intra-abdominal adipose tissue deposition and parity.
AB  - OBJECTIVE: To determine the relationship between body composition/fat
      distribution and parity after adjusting for potential confounders: age, smoking,
      and physical activity. DESIGN: Cross-sectional. SUBJECTS: A total of 170
      Caucasian women between the ages of 18 and 76 years, who were non-smokers with no
      cardiovascular disease, diabetes, metabolic, or endocrine disorders.
      MEASUREMENTS: Physical activity assessment (Baecke Physical Activity
      Questionnaire), anthropometric measures, and body composition (dual-energy X-ray
      absorptiometry, computed tomography). RESULTS: Although percent body fat was
      related to parity (r=0.26, P<0.01), after adjusting for age, physical activity
      index, and smoking, the parity-percent body fat relationship was no longer
      significant. Multiple regression analysis for modeling intra-abdominal adipose
      tissue demonstrated that parity and intra-abdominal adipose tissue were
      significantly related after adjusting for percent body fat, physical activity
      index, and smoking (partial r=0.18, P=0.02, unstandardized beta=5.22+/-2.26,
      intercept=-37.32+/-24.63). CONCLUSION: Our data suggest that intra-abdominal
      adipose tissue increases with increasing parity, even after adjusting for
      potential confounders: age, percent body fat, physical activity, and smoking.

PMID- 16462820
TI  - Simmondsin for weight loss in rats.
AB  - OBJECTIVE: To investigate the safety and efficacy for weight loss of simmondsin,
      a dietary supplement extracted from the seed of the jojoba plant (Simmondsia
      chinensis). ANIMALS: Sprague-Dawley male rats were fed various levels of
      simmondsin for 8 weeks (lean rats) or 16 weeks (high fat-induced obese rats).
      MEASUREMENTS: Food intake, body weight and composition, histopathology,
      hematology parameters. RESULTS: Simmondsin produced a clear dose-response effect
      on food intake and body weight. No remarkable histopathologic changes were noted
      in the liver, kidney and spleen. One lean animal, in the 0.5% group, had
      approximately a 20% depression in red bone marrow cells. Significant effects on
      hematology parameters were seen almost exclusively in groups consuming simmondsin
      at the highest level (0.5%) and these effects appeared to be reversed by removing
      simmondsin from the diet. CONCLUSION: Simmondsin at both the 0.15% level and the
      0.25% level significantly reduced food intake and body weight without apparent
      negative effects. At dose levels much higher than therapeutic levels, there
      seemed to be reversible effects on circulating red and white blood cells. Future
      studies should determine long-term effects of lower doses on blood cell
      parameters.

PMID- 16462821
TI  - Micturition syncope following intermittent catheterisation in a tetraplegic
      patient.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a case of severe hypotension
      and occasional syncope following intermittent catheterisations in a tetraplegic
      patient. SETTING: Department of Spinal Injuries, Berck, France. CASE REPORT: A 47
      year-old man presenting with C7 ASIA B tetraplegia for 9 months, developed
      episodes of severe hypotension and occasional syncope following intermittent
      catheterisations. These episodes were observed in the minutes following the
      catheterisations performed in the sitting position, associating hypotension and
      bradycardia. He was on intermittent catheterisation, had a history of bladder
      hyper-reflexia with some episodes of symptomatic urinary tract infections, of
      mild autonomic dysreflexia (headache, sweating) on high bladder distension, of
      mild orthostatic hypotension, and of reactional depression to the trauma, treated
      with fluoxetine hydrochloride (Prozac). RESULTS: The progressive removal of the
      fluoxetine hydrochloride (Prozac) led to disappearance of the syncope 1 week
      later. Mild hypotension after catheterisations still persisted though, but
      completely disappeared a few months later after further management of bladder
      hyper-reflexia with botulinum-A toxin injections into the detrusor. CONCLUSION:
      In spinal cord injury patients at risk of micturition syncope, care should be
      taken to achieve a gradual decrease in bladder volume, to control bladder hyper
      reflexia and to avoid any medications with orthostatic hypotension's side
      effects.

PMID- 16462822
TI  - Demographics of the Dutch multicenter prospective cohort study 'Restoration of
      mobility in spinal cord injury rehabilitation'.
AB  - STUDY DESIGN: A multicenter prospective cohort study. OBJECTIVE: To compare the
      demographic data of the included population with other studied spinal cord injury
      (SCI) populations in the international literature. SETTING: Eight Dutch
      rehabilitation centers with a specialized SCI unit. METHODS: A total of 205
      individuals with SCI participated in this study. Information about personal,
      lesion and rehabilitation characteristics were collected at the beginning of
      active rehabilitation by means of a questionnaire. RESULTS: The research group
      mainly consisted of men (74%), of individuals with a paraplegia (59%), and had a
      complete lesion (68%). The SCI was mainly caused by a trauma (75%), principally
      due to a traffic accident (42%). The length of clinical rehabilitation varied
      between 2 months and more than a year, which seemed to be dependent on the lesion
      characteristics and related comorbidity. CONCLUSIONS: The personal and lesion
      characteristics of the subjects of the multi-center study were comparable to data
      of other studies, although fewer older subjects and subjects with an incomplete
      lesion were included due to the inclusion criteria 'age' and 'wheelchair
      dependent'. The length of stay in rehabilitation centers in The Netherlands was
      longer compared to Denmark but much longer than in eg Australia and the USA.

PMID- 16462823
TI  - Fertility following spinal cord injury: a systematic review.

PMID- 16462824
TI  - The concept of cure.

PMID- 16462825
TI  - Glioblastoma--more questions than answers?

PMID- 16462826
TI  - The investigational new drug application--who benefits?

PMID- 16462841
TI  - Does temsirolimus have a role in recurrent glioblastoma multiforme?

PMID- 16462842
TI  - Is histologic necrosis in the primary tumor of patients with renal-cell carcinoma
      a predictor for survival?

PMID- 16462843
TI  - Are prostate cancer clinical trial enrollment criteria and endpoints appropriate?

PMID- 16462844
TI  - Does the addition of oxaliplatin increase the risk of capecitabine-induced
      cardiotoxicity?

PMID- 16462845
TI  - Does HER2 overexpression affect response to endocrine therapy in advanced cancer?

PMID- 16462846
TI  - Should women with early hormone-responsive breast cancer be switched from
      tamoxifen to anastrozole?

PMID- 16462847
TI  - Is an aromatase inhibitor more effective than tamoxifen in neoadjuvant endocrine
      therapy for breast cancer?

PMID- 16462848
TI  - Adjuvant postoperative radiotherapy following radical prostatectomy: is now the
      time?

PMID- 16462849
TI  - Therapy insight: Therapeutic challenges in the treatment of elderly cancer
      patients.
AB  - People over the age of 65 years constitute the fastest-growing segment of the US
      population. Within the next 30 years, this group will comprise over 20% of the
      total population. Importantly, 50% of all cancers and 70% of cancer mortality
      occur in this age group. Choosing the correct chemotherapy regimen and dose for
      the older patient can be extremely difficult because of physiological changes
      that occur with aging, as well as other comorbidities associated with this age
      group. Treatment decisions need to be based on a patient's individual
      performance, functional status and life expectancy. Although there are no
      accepted algorithms to guide management decisions in elderly cancer patients,
      data are becoming available that will help guide the use of chemotherapy in the
      older patient population.

PMID- 16462851
TI  - Hypocalcemia associated with bone metastases in a patient with salivary-gland
      carcinoma.
AB  - BACKGROUND: A 70-year-old man presented with a smooth lump on his buccal mucosa
      and right-sided cervical lymphadenopathy. Staging investigations revealed
      extensive sclerotic bone metastases and the patient subsequently underwent
      palliative radiotherapy to the right face and cervical region. Seven months later
      he presented with a 4-day history of fatigue, muscle cramps, ataxia,
      paraesthesia, and blurred vision. INVESTIGATIONS: Physical examination, biopsy of
      abnormal buccal mucosa, routine biochemistry, electrocardiogram, bone scan, CT
      scans of the chest, abdomen and pelvis, and MRI of the brain. DIAGNOSIS:
      Undifferentiated carcinoma of the salivary gland with sclerotic bone metastases
      and hypocalcemia. MANAGEMENT: Palliative radiotherapy to the right face and
      cervical region, infusions of calcium gluconate and calcium chloride, oral
      calcium carbonate, vitamin D and magnesium, palliative chemotherapy (carboplatin
      and 5-fluorouracil), and whole brain radiotherapy.

PMID- 16462850
TI  - Technology insight: Utility of TNF-alpha-based isolated limb perfusion to avoid
      amputation of irresectable tumors of the extremities.
AB  - Isolated limb perfusion (ILP) with melphalan is effective in the treatment of
      small multiple melanoma intransit metastases and is utilized widely for this
      indication. The treatment is much less effective against bulky melanoma
      metastases and has uniformly failed in the treatment of irresectable extremity
      soft tissue sarcomas. The addition of tumor-necrosis factor-alpha (TNF-alpha) to
      this treatment approach has changed the situation dramatically. High response
      rates and limb-salvage rates have been reported in multicenter trials that
      combined ILP with TNF-alpha plus melphalan; these trials resulted in the approval
      of TNF-alpha for bulky melanoma metastases and soft tissue sarcomas in Europe in
      1998. Subsequently, many doctors working in European centers have been trained,
      and a series of confirmatory reports from single institutions have now been
      published regarding the efficacy of the procedure. TNF-alpha has an early and a
      late effect; it enhances tumor-selective drug uptake during the perfusion, and
      plays an essential role in the subsequent selective destruction of the tumor
      vasculature. These effects result in a high response rate in bulky tumors, soft
      tissue sarcomas, bulky melanomas, and various other tumor types. This induction
      therapy therefore allows tumor remnants to be resected some 3 months after ILP
      thus avoiding limb amputation. TNF-alpha-based ILP is a well-established
      treatment that aims to avoid amputations regardless of the tumor size and type.
      It represents an important example of combination therapy that modulates the
      tumor vasculature and should be offered in high-volume tertiary referral centers.

PMID- 16462852
TI  - Paraneoplastic cerebellar degeneration in a woman with ovarian cancer.
AB  - BACKGROUND: A 52-year-old white female presented with sudden onset of light
      headedness followed by diplopia, horizontal vertigo and severe nystagmus with
      oscillopsia. She had previously been in good health. MRI of the brain was normal.
      Lumbar puncture revealed monocytic pleocytosis. During her initial admission, the
      patient improved to some degree and was discharged with a possible diagnosis of
      viral meningitis. After a few weeks, the patient's condition worsened and further
      evaluation was initiated. Examination revealed an unsteady widespread gait,
      severe nystagmus and mild dysarthria. A general and gynecological examination was
      otherwise unremarkable. INVESTIGATIONS: General physical and gynecological
      examinations, MRI of the brain, lumbar punctures, electroencephalogram,
      transvaginal ultrasound, mammogram, tumor markers, anti-neuronal antibodies,
      colonoscopy, whole-body positron emission tomography scan, laparoscopy and
      biopsies. DIAGNOSIS: Stage IIIC endometrioid adenocarcinoma of the ovary with
      paraneoplastic cerebellar degeneration. MANAGEMENT: Tumor cytoreduction,
      plasmapheresis, total abdominal hysterectomy, bilateral salpingo-oophorectomy,
      bilateral pelvic and para-aortic lymph-node dissection, total omentectomy,
      carboplatin and paclitaxel chemotherapy, rehabilitation, and speech therapy.

PMID- 16462853
TI  - Genetic susceptibility to coronary artery disease: from promise to progress.
AB  - Family history is an important independent risk factor for coronary artery
      disease (CAD), and identification of susceptibility genes for this common,
      complex disease is a vital goal. Although there has been considerable success in
      identifying genetic variants that influence well-known risk factors, such as
      cholesterol levels, progress in unearthing novel CAD genes has been slow.
      However, advances are now being made through the application of large-scale,
      systematic, genome-wide approaches. Recent findings particularly highlight the
      link between CAD and inflammation and immunity, and highlight the biological
      insights to be gained from a genetic understanding of the world's biggest killer.

PMID- 16462854
TI  - Teaching resources for genetics.
AB  - Genetics education is essential for preparing the public to engage in an informed
      debate about the future of genetics research and how its applications affect
      human health and the environment. This article provides an overview of genetics
      education resources that are available online, and is relevant to students in
      secondary education, health professionals, geneticists and the public. It also
      describes an integrated approach to teaching genetics, emphasizes the need for
      continuing teacher education, and encourages the involvement of geneticists and
      health professionals in providing a teaching resource.

PMID- 16462855
TI  - Gene therapy progress and prospects: magnetic nanoparticle-based gene delivery.
AB  - The recent emphasis on the development of non-viral transfection agents for gene
      delivery has led to new physics and chemistry-based techniques, which take
      advantage of charge interactions and energetic processes. One of these techniques
      which shows much promise for both in vitro and in vivo transfection involves the
      use of biocompatible magnetic nanoparticles for gene delivery. In these systems,
      therapeutic or reporter genes are attached to magnetic nanoparticles, which are
      then focused to the target site/cells via high-field/high-gradient magnets. The
      technique promotes rapid transfection and, as more recent work indicates,
      excellent overall transfection levels as well. The advantages and difficulties
      associated with magnetic nanoparticle-based transfection will be discussed as
      will the underlying physical principles, recent studies and potential future
      applications.

PMID- 16462858
TI  - Plant-derived antifungal proteins and peptides.
AB  - Plants produce potent constitutive and induced antifungal compounds to complement
      the structural barriers to microbial infection. Approximately 250,000-500,000
      plant species exist, but only a few of these have been investigated for
      antimicrobial activity. Nevertheless, a wide spectrum of compound classes have
      been purified and found to have antifungal properties. The commercial potential
      of effective plant-produced antifungal compounds remains largely unexplored. This
      review article presents examples of these compounds and discusses their
      properties.

PMID- 16462860
TI  - Cell-wall-bound metal ions are not taken up in Neurospora crassa.
AB  - To establish the relevance of the cell wall in metal ion transport, cobalt uptake
      was examined in Neurospora crassa. Cobalt taken up was largely surface bound
      (>90%), resulting in a release of calcium and magnesium. Surface-bound cobalt
      could not enter intracellular locations upon further incubation of mycelia in a
      metal-free medium. Saturation of the surface with one metal augured subsequent
      dose-dependent entry of a different metal into intracellular locations. In
      comparison with the cobalt-resistant mutant, the cobalt-sensitive strain of N.
      crassa bound less cobalt on the surface but with significant intracellular
      accumulation. Our results demonstrate the importance of the cell wall in metal
      transport, toxicity, and resistance in fungi.

PMID- 16462859
TI  - Induction of humoral immunity in response to immunization with recombinant
      Mycobacterium bovis BCG expressing the S1 subunit of Bordetella pertussis toxin.
AB  - Two recombinant Mycobacterium bovis BCG (rBCG) vaccine strains were developed for
      the expression of cytoplasmically located S1 subunit of pertussis toxin, with
      expression driven by the hsp60 promoter of M. bovis (rBCG/pPB10) or the pAN
      promoter of Mycobacterium paratuberculosis (rBCG/pPB12). Both strains showed
      stable expression of equivalent levels of recombinant S1 in vitro and induced
      long-term (up to 8 months) humoral immune responses in BALB/c mice, although
      these responses differed quantitatively and qualitatively. Specifically,
      rBCG/pPB12 induced markedly higher levels of IgG1 than did rBCG/pPB10, and mice
      immunized with the former strain developed specific long-term memory to S1, as
      indicated by the production of high levels of S1-specific IgG in response to a
      sublethal challenge with pertussis toxin 15 months after initial immunization.
      When considered in combination with previous studies, our data encourage further
      evaluation of rBCG as a potential means of developing a low-cost whooping cough
      vaccine based on defined antigens.

PMID- 16462861
TI  - Occurrence and growth characteristics of Escherichia coli and enterococci within
      the accumulated fluid of the northern pitcher plant (Sarracenia purpurea L.).
AB  - Sarracenia purpurea L., a carnivorous bog plant (also known as the pitcher
      plant), represents an excellent model of a well-defined, self-contained
      ecosystem; the individual pitchers of the plant serve as a microhabitat for a
      variety of micro- and macro-organisms. Previously, fecal indicator bacteria
      (Escherichia coli and enterococci) were shown as incidental contaminants in
      pitcher fluid; however, whether their occurrence in pitcher fluid is incidental
      or common has not been established. The purpose of this study was to investigate
      the occurrence, distribution, and growth potential of E. coli and enterococci in
      pitcher plant fluid from a protected bog in northwest Indiana. Escherichia coli
      and enterococci were recovered in pitcher fluids (n=43 plants), with mean
      densities (log CFU mL-1) of 1.28+/-0.23 and 1.97+/-0.27, respectively. In vitro
      experiments showed that E. coli growth in fluid not containing insects or
      indigenous organisms was directly proportional to the fluid concentration (growth
      was 10-fold in 24 h in 100% fluid); however, in the presence of other indigenous
      organisms, E. coli and enterococci were only sustained for 5 days at 26 degrees
      C. Pulsed-field gel electrophoresis (PFGE) analysis showed that the plant
      Enterococcus faecalis isolates were genetically distinct from the human isolates;
      identical PFGE patterns were observed among plant isolates that fell into one of
      six clonal groups. These findings suggest that (i) E. coli and enterococci
      occurrence in pitcher plants is rather common in the bog studied, although their
      originating source is unclear, and (ii) the pitcher fluid contains adequate
      nutrients, especially carbon and energy sources, to promote the growth of
      indicator bacteria; however, under natural conditions, the biotic factors (e.g.,
      competition for nutrients) may restrict their growth.

PMID- 16462862
TI  - DNA fingerprinting analysis of Petromyces alliaceus (Aspergillus section Flavi).
AB  - The objective of this study was to evaluate the ability of the Aspergillus flavus
      pAF28 DNA probe to produce DNA fingerprints for distinguishing among genotypes of
      Petromyces alliaceus (Aspergillus section Flavi), a fungus considered responsible
      for the ochratoxin A contamination that is occasionally observed in California
      fig orchards. P. alliaceus (14 isolates), Petromyces albertensis (one isolate),
      and seven species of Aspergillus section Circumdati (14 isolates) were analyzed
      by DNA fingerprinting using a repetitive sequence DNA probe pAF28 derived from A.
      flavus. The presence of hybridization bands with the DNA probe and with the P.
      alliaceus or P. albertensis genomic DNA indicates a close relationship between A.
      flavus and P. alliaceus. Twelve distinct DNA fingerprint groups or genotypes were
      identified among the 15 isolates of Petromyces. Conspecificity of P. alliaceus
      and P. albertensis is suggested based on DNA fingerprints. Species belonging to
      Aspergillus section Circumdati hybridized only slightly at the 7.0-kb region with
      the repetitive DNA probe, unlike the highly polymorphic hybridization patterns
      obtained from P. alliaceus and A. flavus, suggesting very little homology of the
      probe to Aspergillus section Circum dati genomic DNA. The pAF28 DNA probe offers
      a tool for typing and monitoring specific P. alliaceus clonal populations and for
      estimating the genotypic diversity of P. alliaceus in orchards, vineyards, or
      crop fields.

PMID- 16462863
TI  - Isolation and characterization of chitinases from Verticillium lecanii.
AB  - Degenerate PCR primers corresponding to conserved domains of fungal chitinases
      were designed, and PCR was performed on genomic DNA of the entomogenous fungus
      Verticillium lecanii (Zimmermann) Viegas. Two distinct PCR fragments, chf1 and
      chf2, were isolated and used to identify two DNA contigs. Analyses of these two
      contigs revealed that we had obtained the full-length DNA sequence including the
      promoter, 5' untranslated region, open reading frame (ORF), and 3' untranslated
      regions for two distinct chitinase-like genes. These two genomic DNA sequences
      exhibited 51% identity at the amino acid (aa) level and were designed as acidic
      (chi1) and basic (chi2) chitinase-like genes. The isolated cDNA for chi1 gene is
      1110 bp with a predicted protein of 370 aa and molecular mass of 40.93 kDa, and
      its ORF was uninterrupted in its corresponding genomic DNA sequence. The cDNA for
      the chi2 gene is 1269 bp, a predicted ORF of 423 aa and molecular mass of 45.95
      kDa. In contrast, the ORF was interrupted by three introns in its corresponding
      genomic DNA. The basic chitinase gene (chi2) was successfully expressed in the
      Pichia pastoris system; optimum enzymatic activity was observed at 22 degrees C
      and at pH 7.5. CHI1 and CHI2 were clustered into two different phylogenetic
      groups according to their sequence alignments with 28 other fungal chitinases. A
      chitin-binding domain, comprising two sub-domains that exhibit similarities at
      the aa level to chitin binding domains in bacteria, was identified in 30 fungal
      chitinase sequences examined.

PMID- 16462864
TI  - Aureobasidium pullulans morphology: two adapted polysaccharide stains.
AB  - Morphological stages of Aureobasidium pullulans were investigated utilizing
      different media ingredients and were visualized by bright-field microscopy. A
      polysaccharide stain was developed to stain chlamydospores, cell walls, hyphae,
      and conidia, since current staining techniques do not reveal subcellular details
      to identify fungi, especially those that exhibit polysaccharide secretions.

PMID- 16462865
TI  - Growth of canola (Brassica napus) in the presence of plant growth-promoting
      bacteria and either copper or polycyclic aromatic hydrocarbons.
AB  - Growth of canola (Brassica napus) seeds treated with plant growth-promoting
      bacteria in copper-contaminated and polycyclic aromatic hydrocarbon (PAH)
      contaminated soils was monitored. Pseudomonas asplenii AC, isolated from PAH
      contaminated soil, was transformed to express a bacterial gene encoding 1
      aminocyclopropane-1-carboxylate (ACC) deaminase, and both native and transformed
      bacteria were tested for growth promotion. Inoculation of seeds, grown in the
      presence of copper or creosote, with either native or transformed P. asplenii AC
      significantly increased root and shoot biomass. Native and transformed P.
      asplenii AC and transformed P. asplenii AC encapsulated in alginate were equally
      effective at promoting plant growth in copper-contaminated soils. In creosote
      contaminated soils the native bacterium was the least effective, and the
      transformed encapsulated bacterium was the most effective in growth promotion.

PMID- 16462866
TI  - Scleral biomechanics and glaucoma--a connection?

PMID- 16462867
TI  - Cyclops.

PMID- 16462868
TI  - Visual field expansion in patients with retinitis pigmentosa.
AB  - BACKGROUND: To determine the effectiveness of using spectacle-mounted prisms for
      field expansion in patients with retinitis pigmentosa (RP). METHODS: Vision
      related activities of daily living (V-ADL) questionnaire scores and functional
      visual field score (FFS) measurements were conducted before and after a one-month
      trial of spectacle-mounted prisms in those patients with RP who had residual
      central visual fields of less than 10 degrees. RESULTS: 16 patients were
      recruited who met study inclusion criteria. Mean V-ADL and FFS at baseline were
      67.6 (73%) and 22.9 (46%), respectively. After a 1-month trial using spectacle
      mounted prisms, V-ADL and FFS demonstrated significant improvement to 73.4 (80%,
      p < 0.05) and 27.0 (54%, p < 0.001), respectively. INTERPRETATION: Spectacle
      mounted prisms effectively create visual field expansion and noticeable spatial
      orientation benefits in patients with RP. This may provide an adjunctive tool in
      low vision rehabilitation and should be considered in all cases with RP with less
      than 10 degrees of visual field.

PMID- 16462869
TI  - Photodynamic therapy for subretinal neovascularization in type 2A idiopathic
      juxtafoveolar telangiectasis.
AB  - BACKGROUND: Photodynamic therapy (PDT) with verteporfin is now the standard of
      care worldwide for the treatment of choroidal neovascularization, but has been
      used only rarely in those with subretinal neovascular membranes (SRNVM) due to
      type 2A idiopathic juxtafoveolar retinal telangiectasis (IJT). We performed a
      retrospective study to examine the outcome of patients treated with PDT for SRNVM
      secondary to IJT. METHODS: Retrospective interventional case series of 7 eyes of
      6 IJT patients with SRNVMs treated with PDT. Ophthalmic examination and
      fluorescein angiography were performed before treatment, with retreatment every 3
      months as needed. The main outcome was the proportion of patients avoiding vision
      loss (change of +/- 4 letters, or better). RESULTS: Baseline Snellen acuity
      ranged from 20/40 to 20/400 (median 20/80). Mean follow-up was 21 months.
      Patients received 2.4 treatments on average. Five of 7 patients avoided vision
      loss; acuity improved in 3 eyes (> or = 1 line improvement), stayed the same in 2
      eyes (+/- 4 letters) and decreased in 2 eyes (> or = 1 line decrease) over time.
      Median final acuity was 20/80. Five of 7 eyes had final acuities of > or =
      20/200. No leakage was observed in any eyes following cessation of treatment.

PMID- 16462870
TI  - Pigmentary maculopathy in a patient with Wolfram syndrome.
AB  - CASE REPORT: We describe a rare association of pigmentary maculopathy with
      Wolfram syndrome not previously reported in the literature. A 12-year-old boy
      presented to the retina service with a diagnosis of Wolfram syndrome and a
      history of poor central vision. The patient was found to have bilateral atrophic
      pigmentary maculopathy that was confirmed with fluorescein angiography. COMMENTS:
      Wolfram syndrome may present with a pigmentary maculopathy and this rare finding
      may assist the clinician in making appropriate genetic referral when this
      diagnosis is suspected.

PMID- 16462871
TI  - Identification of visually significant operculum without macular hole by optical
      coherence tomography.
AB  - CASE REPORT: We report a case that illustrates the effectiveness of optical
      coherence tomography (OCT) in identifying visually significant vitreoretinal
      interface opacities in the absence of a macular hole. A patient presented with a
      scotoma in the right eye. Fundoscopic examination revealed a small lesion in
      close proximity to the foveal avascular zone. OCT of the right eye revealed a
      small operculum in the vitreous anterior to the fovea without evidence of a
      macular hole. COMMENTS: To our knowledge, ours is the first reported case of the
      use of OCT to identify the presence of a visually significant operculum without
      an associated macular hole.

PMID- 16462872
TI  - Argon laser trabeculoplasty and reduction of ocular hypotensive medication used
      by glaucoma patients.
AB  - BACKGROUND: We studied the effect of argon laser trabeculoplasty (ALT) on
      medically controlled, pressure-stable glaucoma patients to verify whether it is
      possible to reduce ocular hypotensive medication after ALT while keeping
      intraocular pressure levels similar to those observed before the procedure.
      METHODS: Seventy-one consecutive chronic glaucoma patients, all of whom were
      taking ocular hypotensive medication and had intraocular pressure at adequate
      levels, underwent ALT. After the laser procedure, each patient discontinued one
      hypotensive drug. Mean follow-up was 16.39 +/- 5.39 months. We performed diurnal
      pressure curves on each patient before and after trabeculoplasty to determine the
      effect on intraocular pressure. RESULTS: In 39 (54.9%) patients, it was possible
      to reduce ocular hypotensive medication and still maintain intraocular pressure
      levels similar to those achieved before ALT. INTERPRETATION: For some medically
      controlled, chronic glaucoma patients, ALT can reduce the amount of ocular
      hypotensive medication without significantly altering intraocular pressure.

PMID- 16462873
TI  - Trabeculectomy and phacotrabeculectomy, with mitomycin-C, show similar two-year
      target IOP outcomes.
AB  - BACKGROUND: To determine the efficacy and safety of trabeculectomy with mitomycin
      C (trabMMC) compared with that of single-site phacotrabeculectomy with mitomycin
      C (phacotrabMMC) in glaucoma patients at increased risk for filtering surgery
      failure. METHODS: Eighty-five consecutive eyes that underwent trabMMC and 105
      consecutive eyes that underwent phacotrabMMC were retrospectively compared up to
      2 years postoperatively with respect to intraocular pressure (IOP), number of
      glaucoma medications, and surgical complication rates. The primary outcome was
      the difference in the cumulative proportion of patients meeting the target IOP
      range at 2 years. Secondary outcomes included mean postoperative IOP, mean IOP
      drop from baseline, mean number of glaucoma medications, and surgical
      complication rates. RESULTS: Baseline characteristics were similar in the 2
      groups and most patients had advanced glaucoma with a similar upper limit of the
      target IOP range (15.5 +/- 2.6 mm Hg for trabMMC vs. 15.3 +/- 2.1 mm Hg for
      phacotrabMMC, p = 0.56). Loss to follow-up was significant in both groups (almost
      50% over 2 years). A statistically similar proportion of patients achieved their
      target IOP range at 1 and 2 years in both groups: the cumulative success rate at
      2 years was 29.04% and 22.91% (p = 0.44) without add-on glaucoma therapy, 25.38%
      and 25.22% (p = 0.60) with the use of up to 2 glaucoma medications, and 30.01%
      and 25.17% (p = 0.81) with the use of any number of glaucoma medications, in the
      trabMMC and phacotrabMMC groups, respectively. Mean postoperative IOP was also
      similar between the 2 groups at almost all follow-up times up to 2 years (13.56
      +/- 4.92 mm Hg in trabMMC vs. 13.98 +/- 4.74 mm Hg in phacotrabMMC at 2 years, p
      = 0.67). The mean IOP drop from baseline was significantly greater in the trabMMC
      group throughout the study period (-10.87 +/- 8.33 mm Hg in trabMMC vs. -6.15 +/-
      7.01 mm Hg in phacotrabMMC at 2 years, p = 0.003); however, baseline IOP was also
      higher in the trabMMC group (26.1 mm Hg vs. 20.3 mm Hg, p < 0.0001). Serious
      postoperative complication rates were similarly low between the 2 groups.
      INTERPRETATION: TrabMMC and phacotrabMMC may be equally safe and effective in
      bringing IOP to within an acceptable target range over 2 years in advanced
      glaucoma patients at increased risk for filtering surgery failure, although
      trabMMC appears to be associated with greater IOP lowering from baseline.

PMID- 16462874
TI  - Transmission electron microscopy and autofluorescence findings in the cornea of
      diabetic rats treated with aminoguanidine.
AB  - BACKGROUND: The accumulation of advanced glycation end products (AGEs) has been
      implicated in the pathogenesis of diabetic keratopathy. The present study was
      aimed to understand if aminoguanidine (AG), an AGE inhibitor, was protective
      against the development of corneal complications in a diabetic rat model.
      METHODS: Wistar rats were divided into three experimental groups: control,
      diabetic, and AG-treated diabetic. Diabetes was induced in rats via a single
      intraperitoneal injection (60 mg/kg) of streptozocin (STZ) and AG was
      administered in drinking water at a dose of 1 g/L. All animals were sacrificed at
      the end of 10 weeks and corneas from diabetic and nondiabetic rats were analyzed
      via transmission electron microscopy (TEM). Corneal autofluorescence measurements
      were also performed in all experimental groups. RESULTS: Electron microscopic
      evaluation revealed that aminoguanidine treatment in diabetic rats prevented the
      formation of intracellular spaces between neighbouring cells in the superficial
      corneal epithelium. Hyperglycemia-induced degeneration of intracellular
      organelles and formation of cytoplasmic vacuoles in the corneal stroma was also
      prevented with the treatment of AG. Corneal autofluorescence detected in the
      diabetic group (5.98 +/- 2.17 Fi/mg protein) was found to be significantly
      greater than the control (3.92 +/- 0.56 Fi/mg protein) and the AG-treated
      diabetic group (4.18 +/- 0.59 Fi/mg protein) (p < 0.05). INTERPRETATION: The
      presented data provide evidence that AG is preventive against corneal alterations
      in experimental diabetes.

PMID- 16462875
TI  - Diffuse benign epithelial downgrowth after cataract surgery.
AB  - CASE REPORT: We present an interventional case report of a rare occurrence of
      diffuse epithelial downgrowth developing after extracapsular cataract surgery and
      iris prolapse that was successfully treated only by excision of the membrane. A
      71-year-old man underwent repositioning of an atraumatic iris prolapse 1 month
      after uneventful standard extracapsular cataract extraction in his right eye.
      Over 14 months, a white membrane was observed over almost 80% of the iris
      surface, reducing visual acuity. Intraocular pressure and results of fundus
      examination were normal. Peeling and excision of the membrane were performed.
      Histopathologic analysis was consistent with epithelial downgrowth. At 22 months
      after the epithelial downgrowth peeling, visual acuity was 6/12, there were no
      signs of recurrence, and intraocular pressure was normal without any treatment.
      COMMENTS: Provided a continuous follow-up is possible, simple excision of the
      membrane can be a successful treatment in selected rare cases of diffuse
      epithelial downgrowth.

PMID- 16462877
TI  - Successful conservative management of hydrops with perforation in pellucid
      marginal degeneration.
AB  - CASE REPORT: Hydrops with perforation in the setting of pellucid marginal
      degeneration is a rare complication that is generally treated surgically. We
      report the first case of successful nonsurgical management using only a bandage
      contact lens. COMMENTS: Hydrops with perforation in one eye is a risk factor for
      a similar event occurring in the other eye. Initial conservative management with
      a bandage contact lens should be considered to avoid the risk of surgery. After
      resolution of hydrops, flattening of the cornea and reduced astigmatism is also a
      potential benefit.

PMID- 16462876
TI  - Bilateral acanthamoeba keratitis and treatment strategy based on lesion depth.
AB  - CASE REPORT: This report summarizes a case of bilateral acanthamoeba keratitis in
      an 18-year-old male contact-lens wearer. Early diagnosis is important and
      combination treatment is recommended, tailored to the depth of the lesions.
      COMMENTS: Treatment can be difficult, particularly since amoebic cysts are
      especially resistant. Surgery may be required for advanced cases. Suggestions for
      reducing corneal toxicity to antiamoebic therapy are included.

PMID- 16462878
TI  - Myopic shift from the predicted refraction after sulcus fixation of PMMA
      posterior chamber intraocular lenses.
AB  - BACKGROUND: To evaluate the refractive results of sulcus-fixated
      polymethylmethacrylate (PMMA) posterior chamber intraocular lenses (PC IOLs)
      after cataract surgery with and without posterior capsule complications. METHODS:
      The charts of patients who had undergone cataract surgery were reviewed, and eyes
      that had received sulcus-fixated PMMA PC IOLs were included in the study.
      Postoperative refraction, predicted postoperative refraction for in-the-bag IOL
      with the same diopter, intraoperative posterior capsular complications and
      vitrectomy, axial eye length, incision type (corneal or scleral), and surgery
      type were recorded and analyzed. The difference between actual postoperative
      refraction and predicted refraction for the in-the-bag lens was calculated for
      each patient. RESULTS: Of 143 patients (84 men and 59 women), 162 eyes with a
      sulcus-fixated posterior chamber intraocular lens were investigated. Mean age was
      63.7 +/- 12.1 years. A mean myopic shift of -1.02 +/- 0.96 D from the predicted
      in-the-bag refraction was found. There were no significant differences between
      eyes with or without vitreous loss-vitrectomy (p = 0.8), eyes with scleral or
      corneal incisions (p = 0.11), and eyes having phacoemulsification or
      extracapsular cataract extraction (p = 0.93). In terms of axial length, there
      were no significant differences between long, normal, or short eyes (p = 0.85).
      INTERPRETATION: Sulcus fixation of a PMMA IOL originally planned for in-the-bag
      fixation caused approximately -1.00 D myopic shift in this study. We recommend
      that when sulcus fixation is necessary PMMA IOL power should be approximately
      1.25 to 1.50 D less than the power for in-the-bag fixation. Axial length,
      incision type, vitreous loss and use of vitrectomy, and type of the surgery do
      not appear to alter the postoperative refraction significantly in eyes with
      sulcus fixation.

PMID- 16462879
TI  - Steatocystoma simplex of the caruncle.
AB  - CASE REPORT: The authors present a rare case of steatocystoma simplex occuring in
      the caruncle. A 42-year-old male presented with an asymptomatic, yellow soft mass
      in the medial canthal area of the left eye. An excisional biopsy was performed,
      and the mass lesion was diagnosed as steatocystoma by histological examination.
      COMMENTS: Steatocystoma simplex should be considered one of the differential
      diagnoses for patients with an asymptomatic mass lesion in the caruncle.

PMID- 16462881
TI  - Orbital metastasis from breast carcinoma presenting as neurotrophic keratitis.
AB  - CASE REPORT: This is a case report of an 81-year-old woman with previous breast
      cancer. The patient presented with a history of unilateral painless red eye and
      displayed on examination a nodule in the superior orbital rim, proptosis, and
      neurotrophic keratitis. Clinical and radiographic examinations were followed by
      biopsy of the orbital mass. Computed tomography displayed an extraconal mass
      adjacent to the left superior orbital rim extending to the soft tissues. Light
      microscopy findings suggested the diagnosis of orbital metastatic breast
      carcinoma that was confirmed by immunohistochemistry. The histopathologic
      diagnosis was metastatic adenocarcinoma of the breast to the left orbit.
      COMMENTS: This study emphasizes that orbital metastasis must be considered in
      patients with ocular complaints and neoplastic disease thought to be stable.

PMID- 16462880
TI  - Vision-limiting complications in open-globe injuries.
AB  - BACKGROUND: To correlate vision-limiting complications of open-globe trauma with
      anatomical zone and mechanism of injury. METHODS: Retrospective review of 235
      patients with open-globe injuries at the Massachusetts Eye and Ear Infirmary.
      Vision-limiting complications were assessed at 2 to 3 months after the injury.
      RESULTS: Traumatic cataracts and corneal scarring were the most prevalent vision
      limiting complications in patients with zone I (cornea-only) lacerations. The
      most common vision-limiting factors in eyes with zones II and III lacerations
      (involving sclera) were cataracts and retinal detachments. In patients with
      penetrating injuries, predominant vision-limiting findings were traumatic
      cataracts and corneal scarring. In patients with blunt-force ruptures, leading
      causes were traumatic cataracts and retinal detachments. There were increased
      rates of phthisis and enucleation surgery in patients with ruptures and zones II
      and III injuries. In cases of penetrating and zone I injuries, significantly more
      patients achieved visual acuities better than 20/50 when compared with eyes that
      had ruptures or zones II and III injuries. INTERPRETATION: Traumatic cataracts
      were the most common vision-limiting factor in all subcategories of open-globe
      injuries. Injuries in zones II and III and blunt-force ruptures were associated
      with increased rates of retinal detachments, phthisis, and enucleation,
      contributing to the poorer visual prognosis in these patients.

PMID- 16462882
TI  - Panuveitis as presenting sign of chickenpox in a young child.
AB  - CASE REPORT: A previously healthy 2-year-old girl presented with severe
      panuveitis in her left eye. She developed chickenpox rash several days later. DNA
      particles of varicella-zoster virus (VZV) were detected by polymerase chain
      reaction (PCR) in the aqueous humor. No antiviral regimen was administered. The
      uveitis resolved completely after 1 week. COMMENTS: Patients with chickenpox
      should undergo a thorough ophthalmologic examination at the onset of visual
      symptoms. Clinicians should be aware of the rare occurrence of chickenpox when
      evaluating a uveitis patient. If there is suspicion of chickenpox, the clinician
      may consider ordering serology or PCR tests.

PMID- 16462884
TI  - Study on the interaction of bovine serum albumin with acid cyanine 5R and its
      application in analysis.
AB  - A supramolecular complex of bovine serum albumin (BSA) with acid cyanine 5R (AC
      5R, C.I. acid blue 113, C.I.: 26360) has been shown to form in Tris-HCl buffer
      solution (pH 7.42) by linear sweep voltammetry (LSV), fluorimetry, and
      spectrophotometry. The binding ratio and binding constant of BSA with AC 5R have
      been detected by LSV and fluorimetry. The binding mechanism is also preliminarily
      discussed. In Tris-HCl buffer solution (pH 7.42), AC 5R can easily be reduced on
      the mercury electrode, and it has a well-defined LSV peak current (Ip) and peak
      potential (Ep) at -0.65 V (vs. SCE). In the presence of BSA, the Ip of AC 5R
      decreases, and the peak potential (Ep) shifts to a more positive potential. The
      decrease of the second-order derivative of reductive peak current (deltaIp'') of
      AC 5R is proportional to the logarithm of BSA concentration in the range of 1.54
      x 10(-8) mol x L(-1)-1.54 x 10(-5) mol x L(-1) (r = 0.9931-0.9977). The limit of
      detection of BSA is 9.0 x 10(-9) mol x L(-1). The relative standard deviation is
      1.83% (n = 10), and the standard recovery is 97.5%-104.8%. This method can be
      used to determine BSA concentration on the basis of the interaction of BSA with
      AC 5R.

PMID- 16462885
TI  - Identification of a family of DNA-binding proteins with homology to RNA splicing
      factors.
AB  - We describe a unique family of human proteins that are capable of binding to the
      cAMP regulatory element (CRE) and that are homologous to RNA splicing proteins. A
      human cDNA was isolated that encodes a protein with a distinctive combination of
      modular domain structures: 2 leucine-zipper-like domains, a DNA-binding zinc
      finger-like domain, an RNA-binding zinc-finger-like domain, and 2 coiled-coil
      protein-protein interaction domains. It also has a serine-arginine-rich domain,
      commonly found in proteins involved in RNA splicing. The protein was discovered
      using the CRE as bait in a yeast 1-hybrid assay. It was then shown to bind
      specifically to the CRE in vitro using gel shift assays. We have named the
      protein CRE-associated protein (CREAP). We show that it is widely expressed in
      human tissues but is highly expressed in several fetal tissues and in several
      regions of the adult brain. CREAP is closely related to 2 human proteins of
      unknown function. CREAP shows significant homology with a small nuclear
      ribonucleoprotein of yeast, Luc7p, involved in 5' splice site recognition. The 3
      human CREAP proteins form a unique family with the potential to act as
      transcription factors that link to RNA processing.

PMID- 16462886
TI  - Cytokine-stimulated phosphorylation of GSK-3 is primarily dependent upon PKCs,
      not PKB.
AB  - The regulation of glycogen synthase kinase-3 (GSK-3) by phosphorylation at
      inhibitory sites has been well documented. In many, but not all, cases, the
      phosphatidylinositol 3-kinase pathway, and particularly the downstream kinase
      protein kinase B (PKB)/akt, have been shown to be responsible for GSK-3
      phosphorylation. Given that no studies have ever reported cytokine-mediated
      phosphorylation of GSK-3, we investigated the phosphorylation of this kinase in
      several hemopoietic cell types in response to either interleukin (IL)-3, IL-4 or
      granulocyte-macrophage colony stimulating factor (GM-CSF). Each of the cytokines
      was able to stimulate phosphorylation of the isoforms GSK-3alpha and GSK-3beta.
      However, only in the case of IL-4 stimulation was there any dependence on PKB for
      this phosphorylation. We were clearly able to show that PKB was capable of
      phosphorylating GSK-3 in these cells, but studies using inhibitors of the protein
      kinase C (PKC) family of kinases have shown that these enzymes are more likely to
      play a key role in GSK-3 phosphorylation. Cytokine-mediated generation of
      diacylglycerol was demonstrated, supporting the possible activation of PKC family
      members. Thus, cytokine-dependent GSK-3 phosphorylation in hemopoietic cells
      proceeds primarily through PKB independent pathways.

PMID- 16462887
TI  - Role of osmolytes as chemical chaperones during the refolding of aminoacylase.
AB  - The refolding and reactivation of aminoacylase is particularly difficult because
      of serious off-pathway aggregation. The effects of 4 osmolytes-
      dimethylsulphoxide, glycerol, proline, and sucrose--on the refolding and
      reactivation of guanidine-denatured aminoacylase were studied by measuring
      aggregation, enzyme activity, intrinsic fluorescence spectra, 1-anilino-8
      naphthalenesulfonate (ANS) fluorescence spectra, and circular dichroism (CD)
      spectra. The results show that all the osmolytes not only inhibit aggregation but
      also recover the activity of aminoacylase during refolding in a concentration
      dependent manner. In particularly, a 40% glycerol concentration and a 1.5 mol/L
      sucrose concentration almost completely suppressed the aminoacylase aggregation.
      The enzyme activity measurements revealed that the influence of glycerol is more
      significant than that of any other osmolyte. The intrinsic fluorescence results
      showed that glycerol, proline, and sucrose stabilized the aminoacylase
      conformation effectively, with glycerol being the most effective. All 4 kinds of
      osmolytes reduced the exposure of the hydrophobic surface, indicating that
      osmolytes facilitate the formation of protein hydrophobic collapse. The CD
      results indicate that glycerol and sucrose facilitate the return of aminoacylase
      to its native secondary structure. The results of this study suggest that the
      ability of the various osmolytes to facilitate the refolding and renaturation of
      aminoacylase is not the same. A survey of the results in the literature, as well
      as those presented here, suggests that although the protective effect of
      osmolytes on protein activity and structure is equal for different osmolytes, the
      ability of osmolytes to facilitate the refolding of various proteins differs from
      case to case. In all cases, glycerol was found to be the best stabilizer and a
      folding aid.

PMID- 16462888
TI  - Dose-dependent effect of hydrogen peroxide on calcium mobilization in mouse
      pancreatic acinar cells.
AB  - We have employed confocal laser scanning microscopy to investigate how
      intracellular free calcium concentration ([Ca2+]i) is influenced by hydrogen
      peroxide (H2O2) in collagenase-dispersed mouse pancreatic acinar cells. In the
      absence of extracellular calcium, treatment of cells with increasing
      concentrations of H2O2 resulted in an increase in [Ca2+]i, indicating the release
      of calcium from intracellular stores. Micromolar concentrations of H2O2 induced
      an oscillatory pattern, whereas 1 mmol H2O2/L caused a slow and sustained
      increase in [Ca2+]i. H2O2 abolished the typical calcium release stimulated by
      thapsigargin or by the physiological agonist cholecystokinin octapeptide (CCK-8).
      Depletion of either agonist-sensitive or mitochondrial calcium pools was unable
      to prevent calcium release induced by 1 mmol H2O2/L, but depletion of both stores
      abolished it. Additionally, lower H2O2 concentrations were able to release
      calcium only after depletion of mitochondrial calcium stores. Treatment with
      either the phospholipase C inhibitor U-73122 or the inhibitor of the inositol
      1,4,5-trisphosphate (IP3) receptor xestospongin C did not modify calcium release
      from the agonist-sensitive pool induced by 100 micromol H2O2/L, suggesting the
      involvement of a mechanism independent of IP3 generation. In addition, H2O2
      reduced amylase release stimulated by CCK-8. Finally, either the H2O2-induced
      calcium mobilization or the inhibitory effect of H2O2 on CCK-8-induced amylase
      secretion was abolished by dithiothreitol, a sulphydryl reducing agent. We
      conclude that H2O2 at micromolar concentrations induces calcium release from
      agonist-sensitive stores, and at millimolar concentrations H2O2 can also evoke
      calcium release from the mitochondria. The action of H2O2 is mediated by
      oxidation of sulphydryl groups of calcium ATPases independently of IP3
      generation.

PMID- 16462889
TI  - Isolation and characterization of a new agglutinin from the red marine alga
      Hypnea cervicornis J. Agardh.
AB  - The biochemical characterization of a new lectin (Hypnea cervicornis agglutinin
      or HCA) isolated from the Brazilian red alga H. cervicornis is reported. The
      haemagglutinating activity of the lectin was only inhibited by the glycoprotein
      porcine stomach mucin at a minimum inhibitory concentration of 19 microg x mL(
      1). No haemagglutination inhibition was detected after the addition of simple
      sugars. The MALDI-TOF molecular masses of native and reduced and
      carbamidomethylated HCA were, respectively, 9196.6 Da and 9988.2 Da, indicating
      that the primary structure of the protein is crosslinked by 7 disulfide bonds.
      This unusual structural feature among lectins, along with its N-terminal sequence
      and amino-acid composition, clearly shows that HCA belongs to a protein family
      distinct from the isolectins Hypnin A1 and A2 isolated from the related Japanese
      alga Hypnea japonica. On the other hand, HCA displayed a high degree of
      similarity to the agglutinin from the Brazilian species Hypnea musciformis. Our
      data indicate the occurrence of structural diversity among lectins of closely
      related species living in distant ecosystems, i.e., the Pacific coast of Japan
      and the Atlantic coast of Brazil, and support the hypothesis that the lectin
      content (lectinome) might serve as a biomarker for taxonomical purposes.

PMID- 16462890
TI  - Altered phosphorylation of topoisomerase I following overexpression in an ovarian
      cancer cell line.
AB  - There is a growing interest regarding the use of camptothecins (CPTs) for the
      management of ovarian cancer. Since topoisomerase I has been established as a
      prime target of these drugs in other experimental models, it was important to
      determine whether sensitivity to CPTs in ovarian cancer cells is also correlated
      with the cellular level of this enzyme. Despite the 7-fold increase in
      topoisomerase expression achieved by adenovirus-mediated expression, the
      sensitivity to a CPT derivative (topotecan), was not improved compared with
      control cells harboring an endogenous level of the enzyme. This observation is in
      accordance with the similar level of topoisomerase I activity found in control
      and overexpressing cells and suggests that these cells may efficiently regulate
      the enzyme activity. Indeed, topoisomerase I overexpressing cells are
      characterized by a lack of alkaline phosphatase sensitivity and elimination of
      the hyperphosphorylated form of the protein. Taken together, these observations
      strongly suggest that an alteration in the phosphorylation state of topoisomerase
      I could limit its activity and prevent improvement of CPT response in ovarian
      cancer cells. In addition, a limited extent of topoisomerase I phosphorylating
      activity was found in nuclear extract of OVCAR-3 cells. Hence, providing
      enhancement in topoisomerase I expression may not result in improvement of CPT
      response in ovarian cancer cells because of an efficient control of the
      phosphorylation state of the enzyme.

PMID- 16462891
TI  - The influence of cholesterol and lipid metabolism on host cell structure and
      hepatitis C virus replication.
AB  - The hepatitis C virus (HCV) replicates on a membrane protein complex composed of
      viral proteins, replicating RNA, and altered cellular membranes. Small-molecule
      inhibitors of cellular lipid-cholesterol metabolism such as 25
      hydroxycholesterol, cerulenin, lovastatin, and GGTI-286 all show a negative
      effect on HCV replication. Perturbation of host cell lipid and cholesterol
      metabolism can disrupt replication complexes by altering membranous structures
      where replication occurs. Changes in cholesterol and (or) lipid composition can
      have a general effect on membrane structure. Alternatively, metabolic changes can
      exert a more subtle influence over replication complexes by altering localization
      of host proteins through alterations in lipid anchoring. Here, we use Huh-7 cells
      harboring subgenomic HCV replicons to demonstrate that 25-hydroxycholesterol,
      cerulenin, lovastatin, and GGTI-286 do not disrupt the membranous web where
      replication occurs, whereas cholesterol-depleting agents such as beta
      cyclodextrin do. Cellular imaging suggests that the HCV RNA can remain associated
      with subcellular compartments connected with replication complexes in the
      presence of metabolic inhibitors. Therefore, at least 2 different molecular
      mechanisms are possible for the inhibition of HCV replication through the
      modulation of cellular lipid and cholesterol metabolism.

PMID- 16462893
TI  - Effects of glucose and its modulation by insulin and estradiol on BMSC
      differentiation into osteoblastic lineages.
AB  - It is well known that diabetes affects bone in human and animal models, and leads
      to osteopenia and osteoporosis. Bone-mineral density and other biochemical
      markers of bone turnover are very much affected in people with diabetes. Reduced
      bone mass, occurring with increased frequency in diabetes mellitus, has been
      attributed to poor glycemic control, but the pathogenic mechanisms remain
      unknown. High concentrations of glucose (hyperglycemia) in diabetics leads to
      this complication. Very few in vitro studies using bone-cell lines have been
      carried out to address this problem. In this study, we examined the effects of
      different doses of glucose concentration (5.5, 16.5, and 49.4 mmol/L), alone,
      with insulin (0.6 microg/mL), or with 17beta-estradiol (E2) (10 nmol/L), on rat
      bone-marrow stromal cells (BMSCs) in the presence of an osteogenic medium. BMSC
      proliferation and alkaline phosphatase (ALP) were studied after 3 and 7 d of
      culture, respectively; the area stained for collagen and mineralized nodules was
      studied after 28 d of culture. With high concentrations of glucose, BMSC
      proliferation, ALP activity, the number of nodules formed, and the area stained
      for collagen were greatly reduced. Insulin treatment alone was able to increase
      [3H]-thymidine uptake or ALP activity, whereas both insulin and estradiol were
      able to increase the number of mineralized nodules and the area stained for
      collagen and mineralization. In conclusion, this study suggests that insulin and
      estradiol are able to contain the deleterious effect of high concentrations of
      glucose on BMSC-derived osteoblast proliferation and function.

PMID- 16462892
TI  - Expression and localization of PCSK9 in rat hepatic cells.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9), recently cloned in several
      laboratories, including ours, causes a third form of autosomal dominant
      hypercholesterolemia. Its mechanism of action remains unclear. We studied the
      expression and subcellular localization of PCSK9 in fetal and adult rat tissues
      associated with cholesterol homeostasis using quantitative reverse transcriptase-
      PCR, Western blot analysis, subcellular fractionation, and confocal
      immunofluorescent microscopy. PCSK9 mRNA is most abundant in yolk sac and fetal
      liver, but the highest expression of the protein was found in differentiated
      hepatoma FAO-1 cell line, which also shows the highest expression of LDLR. In FAO
      1 cells PCSK9 expression is downregulated by cholesterol and 25
      hydroxycholesterol and upregulated in the absence of sterols following the same
      pattern of expression as HMG-CoA reductase, synthase, and LDLR. Subcellular
      fractionation, combined with Western blotting, showed that PCSK9 is localized in
      the ER and intermediate vesicular compartment of the cell but not in Golgi
      cisternae. The mature enzyme is secreted from the liver and hepatoma cells.
      Double labeling with antibodies to PCSK9 and LDLR or clathrin revealed some
      colocalization of PCSK9 with clathrin-coated vesicles and LDLR. In conclusion,
      our results show that PCSK9 is processed in the ER, and the mature convertase is
      secreted in the plasma.

PMID- 16462894
TI  - Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma
      cell line Hep G2.
AB  - Monoterpenes have multiple pharmacological effects on the metabolism of
      mevalonate. Geraniol, a dietary monoterpene, has in vitro and in vivo anti-tumor
      activity against several cell lines. We have studied the effects of geraniol on
      growth, fatty-acid metabolism, and mevalonate metabolism in the human
      hepatocarcinoma cell line Hep G2. Up to 100 micromol geraniol/L inhibited the
      growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) reductase
      activity of these cells. At the same concentrations, it increased the
      incorporation of cholesterol from the medium in a dose-dependent manner. Geraniol
      treated cells incorporated less 14C-acetate into nonsaponifiable lipids,
      inhibiting its incorporation into cholesterol but not into squalene and
      lanosterol. This is indicative of an inhibition in cholesterol synthesis at a
      step between lanosterol and cholesterol, a fact confirmed when cells were
      incubated with 3H-mevalonate. The incorporation of 3H-mevalonate into protein was
      also inhibited, whereas its incorporation into fatty acid increased. An
      inhibition of delta5 desaturase activity was demonstrated by the inhibition of
      the conversion of 14C-dihomo-gamma-linolenic acid into arachidonic acid. Geraniol
      has multiple effects on mevalonate and lipid metabolism in Hep G2 cells,
      affecting cell proliferation. Although mevalonate depletion is not responsible
      for cellular growth, it affects cholesterogenesis, protein prenylation, and fatty
      acid metabolism.

PMID- 16462895
TI  - TXM13 human melanoma cells: a novel source for the inhibition kinetics of human
      tyrosinase and for screening whitening agents.
AB  - Research involving whitening agents requires several steps of experimentation,
      and the initial step is to test whitening agents with human melanocytes and those
      with human tyrosinase. Unfortunately, it takes a long time to gather human
      melanocytes, and these cells have some limitations when it comes to performing
      experiments, such as their passage difficulties and their cost. In this study, we
      suggest that the TXM13 human melanoma cells could be a useful cell candidate for
      studying human tyrosinase inhibition and depigmentation. We applied a tyrosinase
      inhibitor, such as dithioglycerine (DTGC), to validate the cell line's
      usefulness, and we tested the effect of DTGC on TXM13 melanogenesis. The results
      showed that human tyrosinase from TXM13 was appropriate, according to the
      inhibition kinetics, and that the conspicuous depigmentation of TXM13 occurred
      after DTGC treatment without downregulating the tyrosinase expression level. When
      taken together, our findings provide useful information regarding the use of the
      TXM13 melanoma cells for the development of whitening agents.

PMID- 16462896
TI  - Integrative strategies to identify candidate genes in rodent models of human
      alcoholism.
AB  - The search for genes underlying alcohol-related behaviours in rodent models of
      human alcoholism has been ongoing for many years with only limited success.
      Recently, new strategies that integrate several of the traditional approaches
      have provided new insights into the molecular mechanisms underlying ethanol's
      actions in the brain. We have used alcohol-preferring C57BL/6J (B6) and alcohol
      avoiding DBA/2J (D2) genetic strains of mice in an integrative strategy combining
      high-throughput gene expression screening, genetic segregation analysis, and
      mapping to previously published quantitative trait loci to uncover candidate
      genes for the ethanol-preference phenotype. In our study, 2 genes, retinaldehyde
      binding protein 1 (Rlbp1) and syntaxin 12 (Stx12), were found to be strong
      candidates for ethanol preference. Such experimental approaches have the power
      and the potential to greatly speed up the laborious process of identifying
      candidate genes for the animal models of human alcoholism.

PMID- 16462897
TI  - Genetic diversity of the Andean tuber-bearing species, oca (Oxalis tuberosa
      Mol.), investigated by inter-simple sequence repeats.
AB  - The Andean tuber-bearing species, Oxalis tuberosa Mol., is a vegetatively
      propagated crop cultivated in the uplands of the Andes. Its genetic diversity was
      investigated in the present study using the inter-simple sequence repeat (ISSR)
      technique. Thirty-two accessions originating from South America (Argentina,
      Bolivia, Chile, and Peru) and maintained in vitro were chosen to represent the
      ecogeographic diversity of its cultivation area. Twenty-two primers were tested
      and 9 were selected according to fingerprinting quality and reproducibility.
      Genetic diversity analysis was performed with 90 markers. Jaccard's genetic
      distance between accessions ranged from 0 to 0.49 with an average of 0.28 +/-
      0.08 (mean +/- SD). Dendrogram (UPGMA (unweighted pair-group method with
      arithmetic averaging)) and factorial correspondence analysis (FCA) showed that
      the genetic structure was influenced by the collection site. The two most distant
      clusters contained all of the Peruvian accessions, one from Bolivia, none from
      Argentina or Chile. Analysis by country revealed that Peru presented the greatest
      genetic distances from the other countries and possessed the highest intra
      country genetic distance (0.30 +/- 0.08). This suggests that the Peruvian oca
      accessions form a distinct genetic group. The relatively low level of genetic
      diversity in the oca species may be related to its predominating reproduction
      strategy, i.e., vegetative propagation. The extent and structure of the genetic
      diversity of the species detailed here should help the establishment of
      conservation strategies.

PMID- 16462898
TI  - Linkage and mapping of resistance genes to Xanthomonas axonopodis pv. passiflorae
      in yellow passion fruit.
AB  - The cultivated passion fruit (Passiflora edulis f. flavicarpa) is a cross
      pollinated species native to South America. In the current study, a segregating
      F1 population derived from a single cross between the clones IAPAR-06 and IAPAR
      123 was used to construct AFLP-based linkage maps and to map resistance genes to
      bacterial spot caused by Xanthomonas axonopodis pv. passiflorae. Linkage analysis
      was performed by the 2-way pseudo-testcross mapping method using markers that
      segregated in a 1:1 ratio. The IAPAR-06 linkage map was constructed using 115
      markers, 112 of which were allocated to 9 linkage groups (LG) covering 790.2 cM.
      The map of IAPAR-123 was constructed using 140 markers, 138 of which were
      allocated to 9 LG covering 488.9 cM. In both maps, clusters of markers were
      detected, indicating that the AFLP markers were not distributed at random.
      Bacterial resistance was assessed by measuring the diseased leaf area after wound
      inoculating the leaves of F1 plants. Quantitative resistance loci (QRLs) mapping
      was carried out by composite interval mapping and 1 QRL was detected, which
      explained 15.8% of the total phenotypic variation. The possibility of considering
      these data for marker-assisted selection in passion fruit breeding programs is
      discussed.

PMID- 16462899
TI  - Mapping genes for resistance to Leptosphaeria maculans in Brassica juncea.
AB  - Blackleg disease of crucifers, caused by the fungus Leptosphaeria maculans, is a
      major concern to oilseed rape producers worldwide. Brassica species containing
      the B genome have high levels of resistance to blackleg. Brassica juncea F2 and
      first-backcross (B1) populations segregating for resistance to a PG2 isolate of
      L. maculans were created. Segregation for resistance to L. maculans in these
      populations suggested that resistance was controlled by two independent genes,
      one dominant and one recessive in nature. A map of the B. juncea genome was
      constructed using segregation in the F2 population of a combination of
      restriction fragment length polymorphism (RFLP) and microsatel lite markers. The
      B. juncea map consisted of 325 loci and was aligned with previous maps of the
      Brassica A and B genomes. The gene controlling dominant resistance to L. maculans
      was positioned on linkage group J13 based on segregation for resistance in the F2
      population. This position was confirmed in the B1 population in which the
      resistance gene was definitively mapped in the interval flanked by pN199RV and
      sB31143F. The provisional location of the recessive gene controlling resistance
      to L. maculans on linkage group J18 was identified using a subset of informative
      F2 individuals.

PMID- 16462900
TI  - Varying signals of the effects of natural selection during teleost growth hormone
      gene evolution.
AB  - The growth hormone (GH) gene of teleost fish exhibits a higher degree of
      variability compared with other vertebrate groups. However, the different
      selective constraints at the sequence level are not well understood. In this
      study, maximum-likelihood (ML) models of codon substitutions were used to
      investigate Darwinian adaptive evolution of the GH gene in teleost fishes.
      Complete GH gene sequences of 54 fish species were classified into 4 orders, and
      the variable nature of GH was examined by determining the dN and dS rate
      variation and the rates of molecular evolution for each teleost order. The
      results indicate that although the overall evolution rate for teleost GH is high
      ((1.15 +/- 0.01) x 10(-9) substitutions/(aa site x y)) compared with the "slow
      phases" in mammals ((0.21 to 0.28 +/- 0.05) x 10(-9)), the vital structure of
      this gene has been retained. While the majority of the amino acid changes appear
      to be due to relaxation of purifying selection, some positively selected sites
      were detected in regions with no specifically identified role in protein
      function. The positively selected regions observed in salmoniformes lineage
      suggests a possible role for positive selection driving functional divergence in
      paralogous forms of the GH gene after whole-genome duplication in this lineage.

PMID- 16462901
TI  - Cloning and characterization of resistance gene analogs from Avena species.
AB  - Sequences analogous to plant resistance genes of the NBS-LRR class were cloned
      from the genomic DNA of 11 Avena species with different genomes and levels of
      ploidy. Three pairs of degenerate primers were used, based on conserved DNA
      sequence motifs belonging to the NBS domain, and 33 sequences were identified.
      These were subdivided into 7 classes depending on nucleotide sequence identity.
      Despite the high level of degeneracy, the primers behaved in a highly selective
      way; the majority of sequences from the different species obtained with every
      primer combination showed strong identity and were considered homologous. For
      most species, only one sequence of each class was identified in each genome,
      suggesting that duplicated sequences are fairly divergent. The strong identity
      among specific NBS sequences precludes any conclusions being made on the
      evolution of these species. The genomic organization of the RGA sequences was
      explored using those of A. strigosa as probes in Southern blots involving
      digested DNA from 15 Avena species. The hybridization patterns showed wide
      diversity both among sequences within a species and among species for each
      sequence. However, the dendrogram generated using the RFLPs showed relationships
      among species to be in good agreement with those previously established using
      other molecular markers.

PMID- 16462902
TI  - Distribution of Ty3-gypsy- and Ty1-copia-like DNA sequences in the genus
      Helianthus and other Asteraceae.
AB  - Two repeated DNA sequences, pHaS13 and pHaS211, which revealed similarity to the
      int gene of Ty3-gypsy retrotransposons and the RNAse-H gene of Ty1-copia
      retroelements, respectively, were surveyed in Asteraceae species and within the
      genus Helianthus. Southern analysis of the genome of selected Asteraceae that
      belong to different tribes showed that pHaS13- and pHaS211-related subfamilies of
      gypsy- and copia-like retroelements are highly redundant only in Helianthus and,
      to a lesser extent, in Tithonia, a Helianthus strict relative. However, under low
      stringency posthybridization washes, bands were observed in almost all the other
      Asteraceae tested when pHaS13 was used as a probe, and in several species when
      pHaS211 was hybridized. FISH analysis of pHaS13 or pHaS211 probes was performed
      in species in which labelling was observed in Southern hybridizations carried out
      under high stringency conditions (Helianthus annuus, Tithonia rotundifolia,
      Ageratum spp., Leontopodium spp., Senecio vulgaris for pHaS13, and H. annuus,
      Tithonia rotundifolia, and S. vulgaris for pHaS211). Scattered labelling was
      observed over all metaphase chromosomes, indicating a large dispersal of both Ty3
      gypsy- and Ty1-copia-like retroelements. However, preferential localization of
      Ty3-gypsy-like sequences at centromeric chromosome regions was observed in all of
      the species studies but one, even in species in which pHaS13-related elements are
      poorly represented. Ty1-copia-like sequences showed preferential localization at
      the chromosome ends only in H. annuus. To study the evolution of gypsy- and copia
      like retrotransposons in Helianthus, cladograms were built based on the Southern
      blot hybridization patterns of pHaS13 or pHaS211 sequences to DNA digests of
      several species of this genus. Both cladograms agree in splitting the genomes
      studied into annuals and perennials. Differences that occurred within the clades
      of perennial and annual species between gypsy- and copia-like retroelements
      indicated that these retrotransposons were differentially active during
      Helianthus speciation, suggesting that the evolution of the 2 retroelement
      families was, within limits, independent.

PMID- 16462903
TI  - Identification of all chromosome arms and their involvement in meiotic
      homoeologous associations at metaphase I in 2 Hordeum vulgare L. x Hordeum
      bulbosum L. hybrids.
AB  - We have identified all Hordeum bulbosum chromosomes in 2 diploid Hordeum vulgare
      x Hordeum bulbosum hybrids using suitable probes and fluorescence in situ
      hybridization. Using the parental idiograms allowed us to carry out a full
      analysis of chromosome associations among all chromosome arms in the hybrids.
      Association frequencies were generally lower for the short arms than for the long
      arms. There were also significant differences among the chromosome arms in
      association frequencies, partly correlated with the absolute length of the
      chromosome arm, as well as with the frequency of recombinant lines, which were
      recovered from partially fertile interspecific hybrids. The H. bulbosum idiogram
      will be useful for further chromosome association studies and will enable the
      identification of H. bulbosum chromosomes involved in chromosome addition or
      substitution lines.

PMID- 16462904
TI  - Molecular characterization and chromosomal mapping of the 5S rRNA gene in Solea
      senegalensis: a new linkage to the U1, U2, and U5 small nuclear RNA genes.
AB  - Some units of the 5S rDNA of Solea senegalensis were amplified by PCR and
      sequenced. Three main PCR products (227, 441, and 2166 bp) were identified. The
      227- and 441-bp fragments were characterized by highly divergent nontranscribed
      spacer sequences (referred to as NTS-I and NTS-II) that were 109 and 324 bp long,
      respectively, yet their coding sequences were nearly identical. The 2166-bp 5S
      rDNA unit was composed of two 5S rRNA genes separated by NTS-I and followed by a
      1721-bp spacer containing the U2, U5, and U1 small nuclear RNA genes (snRNAs).
      They were inverted and arranged in the transcriptional direction opposite that of
      the 5S rRNA gene. This simultaneous linkage of 3 different snRNAs had never been
      observed before. The PCR products were used as probes in fluorescence in situ
      hybridization experiments to locate the corresponding loci on the chromosomes of
      S. senegalensis. A major 5S rDNA chromosomal site was located along most of the
      short arm of a submetacentric pair, while a minor site was detected near the
      centromeric region of an acrocentric pair.

PMID- 16462905
TI  - DNA methylation, histone H3 methylation, and histone H4 acetylation in the genome
      of a crustacean.
AB  - In this work, we used antibodies against histone H3 trimethylated at lysine 9
      (H3K9m3); against histone H4 acetylated at lysines 5, 8, 12, and 16 (H4ac); and
      against DNA methylated at 5C cytosine (m5C) to study the presence and
      distribution of these markers in the genome of the isopod crustacean Asellus
      aquaticus. The use of these 3 antibodies to immunolabel spermatogonial metaphases
      yields reproducible patterns on the chromosomes of this crustacean. The X and Y
      chromosomes present an identical banding pattern with each of the antibodies. The
      heterochromatic telomeric regions and the centromeric regions are rich in H3K9m3,
      but depleted in m5C and H4ac. Thus, m5C does not seem to be required to stabilize
      the silence of these regions in this organism.

PMID- 16462906
TI  - 5S rDNA gene diversity in tea (Camellia sinensis (L.) O. Kuntze) and its use for
      variety identification.
AB  - Variability in the organization of repeats of 5S rDNA is useful for phylogenetic
      studies in various crops. We found variable repeats of 5S rDNA gene in the genome
      of tea (Camellia sinensis (L.) O. Kuntze) during Southern hybridization.
      Variability in the repeats of 5S rDNA with specific restriction endonucleases
      (Sau3AI, BamHI, and ApoI) was analyzed in 28 different tea clones representing 3
      types of tea. Our results clearly show that the 5S rDNA gene in tea could be used
      as a molecular marker to distinguish C. sinensis Chinary tea from the other
      important types of tea, namely Assamica and Cambod. Upon analysis with
      restriction endonucleases, the 5S rDNA gene in the tea genome was found to be
      heavily methylated.

PMID- 16462907
TI  - Molecular defects in cardiac myofibrillar proteins due to thyroid hormone
      imbalance and diabetes.
AB  - The heart very often becomes a victim of endocrine abnormalities such as thyroid
      hormone imbalance and insulin deficiency, which are manifested in a broad
      spectrum of cardiac dysfunction from mildly compromised function to severe heart
      failure. These functional changes in the heart are largely independent of
      alterations in the coronary arteries and instead reside at the level of
      cardiomyocytes. The status of cardiac function reflects the net of underlying
      subcellular modifications induced by an increase or decrease in thyroid hormone
      and insulin plasma levels. Changes in the contractile and regulatory proteins
      constitute molecular and structural alterations in myofibrillar assembly, called
      myofibrillar remodeling. These alterations may be adaptive or maladaptive with
      respect to the functional and metabolic demands on the heart as a consequence of
      the altered endocrine status in the body. There is a substantial body of
      information to indicate alterations in myofibrillar proteins including actin,
      myosin, tropomyosin, troponin, titin, desmin, and myosin-binding protein C in
      conditions such as hyperthyroidism, hypothyroidism, and diabetes. The present
      article is focussed on discussion how myofibrillar proteins are altered in
      response to thyroid hormone imbalance and lack of insulin or its responsiveness,
      and how their structural and functional changes explain the contractile defects
      in the heart.

PMID- 16462908
TI  - Eugenol-induced contractions of saponin-skinned fibers are inhibited by heparin
      or by a ryanodine receptor blocker.
AB  - The effects of eugenol on the sarcoplasmic reticulum (SR) and contractile
      apparatus of chemically skinned skeletal muscle fibers of the frog Rana
      catesbeiana were investigated. In saponin-skinned fibers, eugenol (5 mmol/L)
      induced muscle contractions, probably by releasing Ca(2+) from the SR. The Ca(2+)
      induced Ca(2+) release blocker ruthenium red (10 micromol/L) inhibited both
      caffeine- and eugenol-induced muscle contractions. Ryanodine (200 micromol/L), a
      specific ryanodine receptor/Ca(2+) release channel blocker, promoted complete
      inhibition of the contractions induced by caffeine, but only partially blocked
      the contractions induced by eugenol. Heparin (2.5 mg/mL), an inositol 1,4,5
      trisphosphate (InsP3) receptor blocker, strongly inhibited the contractions
      induced by eugenol but had only a small effect on the caffeine-induced
      contractions. Eugenol neither altered the Ca(2+) sensitivity nor the maximal
      force in Triton X-100 skinned muscle fibers. These data suggest that muscle
      contraction induced by eugenol involves at least 2 mechanisms of Ca(2+) release
      from the SR: one related to the activation of the ryanodine receptors and another
      through a heparin-sensitive pathway.

PMID- 16462909
TI  - Chunghyuldan activates NOS mRNA expression and suppresses VCAM-1 mRNA expression
      in human endothelial cells.
AB  - Chunghyuldan (CHD), a combinatorial drug that has antihyperlipidemic and anti
      inflammatory activities, has been shown to improve arterial stiffness and inhibit
      stroke recurrence in clinical study. To understand the molecular basis of CHD's
      clinical effects, we explored its effect on cell proliferation and expression of
      nitric oxide synthase (NOS) and vascular cell adhesion molecule (VCAM-1) in human
      umbilical vein endothelial cells (HUVECs). Cell number counting and [3H]thymidine
      incorporation assay demonstrated that nontoxic doses of CHD have an inhibitory
      effect on DNA synthesis and suppress cell cycle progression of HUVECs. CHD
      treatment led to a marked induction of NO production through up-regulation of NOS
      mRNA expression in a dose- and time-dependent manner, whereas it suppressed VCAM
      1 expression. CHD inhibition of VCAM-1 expression was totally blocked by
      pretreatment with the NO synthesis inhibitor L-NMMA, whereas pretreatment with
      the NO donor DETA-NO further decreased VCAM-1 level in CHD-treated HUVECs,
      indicating that VCAM-1 regulation by CHD is mediated through increased NO
      synthesis by CHD. In addition, TNF-alpha-mediated VCAM-1 activation was
      substantially impeded by CHD treatment. Collectively, our data suggest that anti
      inflammatory or anti-hyperlipidemic effects of CHD might be associated with its
      ability to activate NO production and suppress VCAM-1 expression in human
      endothelial cells.

PMID- 16462910
TI  - Serial magnetic resonance imaging based assessment of the early effects of an ACE
      inhibitor on postinfarction left ventricular remodeling in rats.
AB  - In vivo assessment of treatment efficacy on postinfarct left ventricular (LV)
      remodeling is crucial for experimental studies. We examined the technical
      feasibility of serial magnetic resonance imaging (MRI) for monitoring early
      postinfarct remodeling in rats. MRI studies were performed with a 7-Tesla unit,
      1, 3, 8, 15, and 30 days after myocardial infarction (MI) or sham operation, to
      measure LV mass, volume, and the ejection fraction (EF). Three groups of animals
      were analyzed: sham-operated rats (n = 6), MI rats receiving lisinopril (n = 11),
      and MI rats receiving placebo (n = 8). LV dilation occurred on day 3 in both MI
      groups. LV end-systolic and end-diastolic volumes were significantly lower in
      lisinopril-treated rats than in placebo-treated rats at days 15 and 30. EF was
      lower in both MI groups than in the sham group at all time points, and did not
      differ between the MI groups during follow-up. Less LV hypertrophy was observed
      in rats receiving lisinopril than in rats receiving placebo at days 15 and 30. We
      found acceptable within- and between-observer agreement and an excellent
      correlation between MRI and ex vivo LV mass (r = 0.96; p < 0.001). We
      demonstrated the ability of MRI to detect the early beneficial impact of
      angiotensin-converting enzyme (ACE) inhibitors on LV remodeling. Accurate and
      noninvasive, MRI is the tool of choice to document response to treatment
      targeting postinfarction LV remodeling in rats.

PMID- 16462911
TI  - Glyceryl trinitrate-induced angiotensin-converting enzyme (ACE) inhibition in
      healthy volunteers is dependent on ACE genotype.
AB  - Evidence concerning the importance of angiotensin-converting enzyme (ACE)
      genotype in cardiovascular diseases is accumulating. The aim of this study was to
      investigate if nitric oxide (NO), generated from glyceryl trinitrate (GTN),
      affects human serum ACE activity in vivo, and if so, whether this effect was
      dependent on ACE genotype and (or) reflected in blood pressure reduction. A
      tablet containing 5 mg GTN was bucally administered for 5 minutes to 17 healthy
      volunteers. Blood pressure (BP) was recorded, and serum ACE activity, ACE
      genotype, and plasma cGMP was analyzed. GTN administration significantly reduced
      BP only in individuals with the deletion/deletion (DD) genotype. Sixty minutes
      after GTN administration, serum ACE activity was reduced in individuals with the
      insertion/insertion (II) and insertion/deletion (ID) genotypes, but not the DD
      genotype. Comparing the change in ACE activity over time between the genotypes
      resulted in the following: II vs. DD, p < 0.01; II vs. ID, p < 0.05; and ID vs.
      DD, p < 0.05. There was no significant difference in plasma cGMP content neither
      between the ACE genotypes nor before and after GTN administration. In conclusion,
      GTN inhibits serum ACE in vivo in individuals with the II and ID, but not the DD
      genotype.

PMID- 16462912
TI  - Expression of the chloride channel CLC-K in human airway epithelial cells.
AB  - Airway submucosal gland function is severely disrupted in cystic fibrosis (CF),
      as a result of genetic mutation of the cystic fibrosis transmembrane conductance
      regulator (CFTR), an apical membrane Cl(-) channel. To identify other Cl(-)
      channel types that could potentially substitute for lost CFTR function in these
      cells, we investigated the functional and molecular expression of Cl(-) channels
      in Calu-3 cells, a human cell line model of the submucosal gland serous cell.
      Whole cell patch clamp recording from these cells identified outwardly rectified,
      pH- and calcium-sensitive Cl(-) currents that resemble those previously ascribed
      to ClC-K type chloride channels. Using reverse transcription polymerase chain
      reaction, we identified expression of mRNA for ClC-2, ClC-3, ClC-4, ClC-5, ClC-6,
      ClC-7, ClC-Ka, and ClC-Kb, as well as the common ClC-K channel beta subunit
      barttin. Western blotting confirmed that Calu-3 cells express both ClC-K and
      barttin protein. Thus, Calu-3 cells express multiple members of the ClC family of
      Cl(-) channels that, if also expressed in native submucosal gland serous cells
      within the CF lung, could perhaps act to partially substitute lost CFTR function.
      Furthermore, this work represents the first evidence for functional ClC-K
      chloride channel expression within the lung.

PMID- 16462913
TI  - The alpha1-adrenergic receptor not the DA(1)-dopaminergic receptor mediates
      cyclosporine-SKF38393 renovascular interaction.
AB  - In this study, we investigated the effect of acute exposure to cyclosporine A
      (CyA) on renal vasodilations evoked by the DA(1) dopaminergic agonist SKF38393
      and whether dopamine DA(1) receptors are directly involved in the interaction.
      Changes evoked by CyA in SKF38393 vasodilations were evaluated in phenylephrine
      preconstricted isolated perfused rat kidneys in the absence and presence of
      SCH23390, a DA(1) receptor antagonist. SKF38393 (3 x 10(-8) to 3 x 10(-6) mol)
      produced dose-dependent reductions in the renal perfusion pressure that were
      significantly attenuated in tissues pretreated with SCH23390 or CyA. Unlike
      SKF38393, the vasodilatory action of sodium nitroprusside, a nitrovasodilator,
      was not altered by CyA. The attenuating effect of CyA on SKF38393 vasodilations
      was preserved in preparations pretreated with SCH23390, suggesting that sites
      other than DA(1) receptors may be involved in CyA-SKF38393 interaction. The study
      was then extended to investigate the possible involvement of renal alpha1
      adrenoceptors in the interaction. Blockade of alpha(1)-adrenoceptors by prazosin
      (30 nmol/L) significantly reduced the vasodilatory effect of SKF38393 and
      virtually abolished the CyA-induced attenuation of SKF38393 responses. Further,
      CyA failed to alter SKF38393 vasodilations when the renal tone was raised with
      prostaglandin F2alpha (PGF2alpha), a vasoconstrictor whose effect is independent
      of alpha(1)-adenoceptors. Together, these findings support earlier reports that
      both DA(1) and alpha(1)-receptors mediate the renal vasodilatory action of
      SKF38393 and suggest that CyA interacts selectively with the alpha(1)-receptor
      component to compromise SKF38393 responses.

PMID- 16462914
TI  - Rofecoxib and tramadol do not attenuate delayed-onset muscle soreness or
      ischaemic pain in human volunteers.
AB  - We assessed the effect of rofecoxib, a cyclo-oxygenase-2 inhibitor, and tramadol,
      a centrally acting analgesic, on both delayed-onset muscle soreness (DOMS) and
      experimentally induced ischaemic pain. We induced DOMS in 10 male and 5 female
      healthy volunteers by downhill running for 30 min at a 12% decline and a speed of
      9 km x h(-1). We also induced ischaemic pain by finger movements with an arterial
      tourniquet around the arm. In a randomized, double-blind crossover format, we
      administered rofecoxib (50 mg, daily), tramadol (50 mg, 3 times per day), and a
      placebo (orally for 3 days), starting immediately after exercise. A 100 mm visual
      analogue scale (VAS) and McGill pain questionnaire were used to describe muscle
      soreness and ischaemic forearm pain 24 h after the exercise. The pressure pain
      threshold (PPT) in the thigh and ischaemic pain tolerance in the forearm were
      measured before exercise and 24 and 72 h after exercise. PPT decreased 24 h after
      exercise, compared with pre-exercise values (ANOVA, p < 0.05), but neither drug
      had any significant effect on the PPT. Neither rofecoxib nor tramadol had any
      effect on time of ischaemia tolerated or amount of finger activity during
      ischaemia. The VAS and pain-rating index, for both muscle soreness and
      experimental ischaemic pain, were not affected significantly by either drug. Both
      DOMS and ischaemic pain share peripheral and central mechanisms, yet neither are
      attenuated by rofecoxib or tramadol.

PMID- 16462915
TI  - [Regulation of blood volume during weightlessness simulation of long duration].
AB  - To study the effects of microgravity on the mechanisms involved in the regulation
      of body hydrous status, total body water (TBW), plasma volume (PV), and its main
      regulating hormones (plasma renin, aldosterone, atrial natriuretic peptide (ANP),
      anti-diuretic hormone (ADH)) were determined, by isotopic dilution, Dill and
      Costill's formula, and radio-immunologic dosages, in 9 male subjects submitted to
      a 90-d head-down bed rest (HDBR). ADH was determined in 24 h urinary collection
      as well as osmolality, sodium, and potassium. Body mass decreased (-2.8 +/- 0.8
      kg) as well as TBW(-7.2% +/- 0.9%, i.e., -2.6 +/- 0.7 kg) and PV (-4.7% +/-
      1.8%). Renin and aldosterone were enhanced (+109.0% +/- 15.4% and +87.2% +/-
      38.9%, respectively). Simultaneously, we observed a decrease in ANP (-33.2% +/-
      20.4%). Other variables, including ADH, were not affected by HDBR. Body mass and
      TBW decrease (and consequently lean body mass) are associated with muscle
      atrophy. Renin, aldostrerone, and ANP modifications are well explained by the
      decrease in PV, which was not enough to induce ADH changes. It suggests that in
      man, the main regulatory factor for ADH secretion is osmolality, when PV is
      modestly and progressively decreased without arterial pressure modification,
      which was the case in the present protocol.

PMID- 16462916
TI  - PHARMAC and lack of funding for clopidogrel.
AB  - Clopidogrel is an antiplatelet drug that has been shown in several trials to
      reduce clinical events such as cardiovascular death, stroke, and myocardial
      infarction when compared to aspirin in a broad range of patients with
      atherosclerotic vascular disease. Clopidogrel has also been shown to reduce the
      same events by 20% when added to aspirin in patients with unstable angina and
      also in patients undergoing coronary artery stenting. Despite this information
      being available for 5 to 10 years, guideline recommendations, and the knowledge
      that 5% of patients have major allergy to aspirin, New Zealand patients have only
      been able to receive funded clopidogrel for a short period, typically 3 weeks,
      after coronary artery stenting. We believe this is an example where New
      Zealanders have been denied treatments, despite a strong evidence-base, by
      PHARMAC's actions of delaying the funding of new drugs. We need to have a better
      process whereby New Zealanders can rapidly access new treatments.

PMID- 16462918
TI  - Gestational diabetes mellitus: time for consensus on screening and diagnosis.

PMID- 16462919
TI  - Pacific healthcare workers and their treatment interventions for Pacific clients
      with alcohol and drug issues in New Zealand.
AB  - AIM: To provide an overview of the treatment interventions and practices of
      Pacific alcohol and other drugs (AOD) services in New Zealand. METHODS: Face-to
      face interviews were conducted with 31 Pacific staff members from 13 services
      registered with the Alcohol Advisory Council of New Zealand National Directory.
      Issues around assessment, treatment interventions, outcome measures, service
      structure, and resources were explored. RESULTS: Overall, the practices in
      District Health Board (DHB) and Non-Government Organisation (NGO) Pacific
      services were found to be similar. The clinical concepts of assessment,
      treatment, and outcome measures were not clearly understood by Pacific workers.
      This was due to the lack of attention towards Pacific concepts and practices and
      values. A holistic approach was viewed to be the best approach when working with
      Pacific clients based on health belief models, such as the Fonofale model.
      CONCLUSIONS: The findings of this study provide baseline data of treatment
      interventions and service practices of Pacific AOD services. There appears to be
      a Pacific way of working with Pacific clients. The most effective worker for
      Pacific people is someone who has sound knowledge of AOD, Pacific cultures and
      processes, and has the ability to integrate both Palangi (European) and Pacific
      knowledge to help the client.

PMID- 16462920
TI  - Medical Image. Combined FDG-PET/CT and CT-guided biopsy in diagnosing oesophageal
      cancer recurrence.

PMID- 16462921
TI  - Carcinomas in the Bay of Plenty: incomplete excision rates.

PMID- 16462922
TI  - Pacific Islands Families: First Two Years of Life Study--design and methodology.
AB  - AIMS: Knowledge about the health, psychosocial, and behavioural characteristics
      of Pacific peoples with young children resident in New Zealand is limited. The
      Pacific Islands Families: First Two Years of Life (PIF) Study was designed to
      redress this knowledge gap. This paper describes the design and methodology of
      the PIF Study. METHODS: Mothers of Pacific infants born at Middlemore Hospital
      between 15 March and 17 December 2000 were recruited. Maternal home interviews
      covering sociodemographic, cultural, environmental, child development, family and
      household dynamics, childcare, lifestyle, and health issues were undertaken at
      approximately 6-weeks, 12-months, and 24-months postpartum. Paternal home
      interviews and child development assessments were conducted at approximately 12
      months and 24-months postpartum. Information from Middlemore's Hospital Discharge
      Summary records and Plunket's 6-week and 6-month assessments was also captured.
      RESULTS: 1708 mothers were identified, 1657 were invited to participate, 1590
      (96%) consented to a home visit; and, of these, 1,477 (93%) were eligible for the
      PIF study. Of those eligible, 1,376 (93%) participated at 6-weeks, 1224 (83%)
      participated at 12-months, and 1144 (77%) participated at 24-months. No important
      differential attrition was observed. Paternal interviews and child assessments
      were conducted on 825 fathers and 1241 infants at 12-months and on 757 fathers
      and 1064 children at 24-months. CONCLUSIONS: The PIF study is a large,
      scientifically and culturally robust longitudinal study that has achieved
      respectable participation rates in a historically hard-to-reach population. We
      believe that results from this study will inform future policy development within
      New Zealand.

PMID- 16462923
TI  - Pseudoaneurysm of the internal carotid artery in an infant aged 8 months.
AB  - Pseudoaneurysm of the carotid artery is a potentially life-threatening
      complication of deep neck space infection. It clinically manifests by pulsatile
      neck swelling, lower cranial nerve palsy, and Horner's syndrome. There may be
      sentinel bleed from nose or oral cavity before the massive haemorrhage, from
      carotid artery rupture. We present a case of pseudoaneurysm of the internal
      carotid artery (ICA) following parapharyngeal and retropharyngeal space infection
      in an 8-month-old infant. Emergency carotid artery ligation was performed and the
      infant recovered well without any neurological sequelae.

PMID- 16462925
TI  - Domestic violence as witnessed by New Zealand children.
AB  - BACKGROUND: This study reports on domestic violence in New Zealand families
      witnessed by members of the Dunedin Multidisciplinary Health and Development
      Study. METHOD: Questions on the witnessing of father to mother and mother to
      father physical violence and threats of harm up to the age of 18 were included in
      a retrospective family violence interview carried out when the cohort was
      interviewed at age 26. Study members who reported violence between parents were
      asked about the nature, context, and consequences of this violence. RESULTS: One
      quarter (24%) of the sample reported violence or threats of violence directed
      from one parent to the other. Nine percent reported infrequent assaults while one
      in 10 reported more than five acts of physical violence. In violent families, 55%
      reported violence by fathers only, 28% by both partners, and 16% by mothers only.
      Almost 90% of the exposed group witnessed violence between natural parents, and
      80% were exposed to violence before the age of 11. The gender of the study member
      or parent did not predict how upset study members were, but frequency of violence
      did. Witnesses were more likely than non-witnesses to have diagnoses of anxiety
      and depression at age 21. Socioeconomic status and age of parents were related to
      violence patterns, but not the mother's education or employment status.
      CONCLUSION: This study suggests that a quarter of young adults have been exposed
      to acts or threats of violence carried out by one parent toward another parent,
      and the majority found such witnessing to be a very upsetting experience. Public
      education programmes should emphasise that all violence carries risk of harm to
      all family members.

PMID- 16462924
TI  - Contraceptive use by Maori youth in New Zealand: associated risk and protective
      factors.
AB  - AIMS: To identify risk and protective factors associated with consistent
      contraception use by sexually active Maori youth. METHODS: Secondary analysis was
      undertaken utilising Youth2000, an anonymous nationally representative secondary
      school health and wellbeing survey, undertaken in 2001. We describe the self
      reported sexual health and contraceptive use behaviours of Maori students. A
      multiple logistic regression model was utilised to identify risk and protective
      factors associated with consistent contraception use by sexually active Maori
      students. RESULTS: Half of the Maori students have had sexual intercourse (54%
      males; 48% females) and a third are currently sexually active (33% males; 34%
      females). Most Maori youth who have ever had sex use condoms for contraception
      (82%) and most sexually active Maori youth reported consistent use of
      contraception (71% males; 70% females). Maori youth who use contraception
      consistently are more likely to report getting enough time with a parent (OR
      1.50; 95% CI 1.05-2.14; p=0.03) and less likely to report weekly marijuana use
      (OR 0.53; 95% CI 0.37-0.76; p=0.0006). CONCLUSIONS: Consistent use of condoms is
      a common self-reported contraceptive practice by many young Maori. However this
      behaviour is not universal, and in view of the significant sexual and
      reproductive health disparities that exist for Maori youth, sexual and
      reproductive health programs should examine a broader strategy of promoting
      protective factors such as strengthening youth-parent relationships and reducing
      risk factors, such as minimising substance misuse. Together with existing efforts
      in education, whanau (family), and community based programs, these strategies may
      support healthier sexual health outcomes for Maori youth.

PMID- 16462926
TI  - On the receiving end: young adults describe their parents' use of physical
      punishment and other disciplinary measures during childhood.
AB  - AIM: To investigate the prevalence, nature, and context of physical punishment
      and other forms of parental discipline, as reported by study members (SMs) of the
      Dunedin Multidisciplinary Health and Development Study. METHODS: 962 26-year-old
      adults (born in Dunedin, New Zealand) were interviewed about their experiences of
      discipline in childhood. Study members were asked about the usual forms of
      punishment received in primary and secondary school years, as well as the worst
      punishment they ever received. Details regarding the study members' reactions to
      different punishments were collected. Variables related to the person
      administering the punishment were also investigated. RESULTS: Of the study
      members providing data, 80% reported receiving physical punishment at some time
      during childhood: 29% identifying smacking; 45% reporting being hit with an
      object; and 6% reporting extreme physical punishment as the most severe form.
      Physical punishment on a regular basis was reported by 71% of study members.
      Results varied by age with more study members reporting physical punishment in
      primary school years. However, the number of study members experiencing physical
      punishment in adolescence was still high, at 47%. Significant gender differences
      were found in reported punishment, with more girls smacked, and more boys hit
      with an object in primary school years. Punisher-related reports showed that
      mothers were significantly more likely to employ non-physical forms of punishment
      whereas fathers were significantly more likely to use extreme physical
      punishment. CONCLUSION: For many New Zealanders, experiences of physical
      punishment during childhood are very much the norm. These findings have
      implications for the young adults studied as they now enter the parenting years
      and for efforts aimed at prevention and early intervention for at-risk groups.

PMID- 16462927
TI  - Type 1 diabetes: research hopes and their New Zealand implications.

PMID- 16462929
TI  - Resuscitation training of newly-qualified doctors.

PMID- 16462928
TI  - Differences in health-related socioeconomic characteristics among Pacific
      populations living in Auckland, New Zealand.
AB  - AIM: To describe, compare and contrast the health-related socioeconomic
      characteristics of the different Pacific ethnic groups surveyed in the Auckland
      Diabetes, Heart and Health Survey (DHHS). METHODS: The DHHS was carried out in
      Auckland in 2002-2003. Electoral roll based sampling and cluster sampling
      strategies were used to recruit a representative sample of Auckland Pacific
      populations. Participants answered a self-administered questionnaire about their
      demographic and socioeconomic position. RESULTS: The study surveyed 1011 Pacific
      people aged between 35-74 years of age. Of the 1011 Pacific participants, 484
      were of Samoan, 255 Tongan, 116 Cook Island, 109 Niuean, 26 Fijian, and 21 were
      of 'Other Pacific' ethnic groups. Samoans were least likely to have no children,
      and most likely to hold a certificate qualification. Tongans were least likely to
      be born in New Zealand (NZ) and had the shortest residence time in NZ. Tongans
      were most likely to be married and had the largest families. Cook Islanders were
      most likely to be NZ-born and had the highest household income. Niueans were most
      likely to be in paid employment, to hold a diploma qualification, to own their
      own homes, and have the smallest families. CONCLUSIONS: In conclusion, a distinct
      pattern (continuum) emerged from the results. The Cook Island and Niuean ethnic
      groups generally had a similar and more favourable socioeconomic profile compared
      to the Samoan and Tongan ethnic groups. These differences are most likely to be
      related to the length of residence in NZ. As differences existed, each Pacific
      ethnic group should be investigated separately when there are sufficient numbers.

PMID- 16462930
TI  - Ethnic differences in nicotine use in New Zealand--chromosomes or colonisation?

PMID- 16462931
TI  - Towards a 3-day hospital stay for right hemicolectomy.

PMID- 16462932
TI  - A lump behind the knee.

PMID- 16462933
TI  - Family violence in New Zealand: we can do better.

PMID- 16462934
TI  - Medical audit of practice management of diabetes in pregnancy at Gisborne
      Hospital's Obstetric Medical Service.

PMID- 16462935
TI  - Survey by a Gisborne GP to detect diabetes in his patients.

PMID- 16462936
TI  - Statins and myopathy: a patient's experience.

PMID- 16462937
TI  - Risk of perioperative COX-2-inhibitor treatment: is a systematic review
      appropriate?

PMID- 16462938
TI  - More on PHARMAC and tobacco control in New Zealand.

PMID- 16462939
TI  - Traditional biomolecular structure determination by NMR spectroscopy allows for
      major errors.
AB  - One of the major goals of structural genomics projects is to determine the three
      dimensional structure of representative members of as many different fold
      families as possible. Comparative modeling is expected to fill the remaining gaps
      by providing structural models of homologs of the experimentally determined
      proteins. However, for such an approach to be successful it is essential that the
      quality of the experimentally determined structures is adequate. In an attempt to
      build a homology model for the protein dynein light chain 2A (DLC2A) we found two
      potential templates, both experimentally determined nuclear magnetic resonance
      (NMR) structures originating from structural genomics efforts. Despite their high
      sequence identity (96%), the folds of the two structures are markedly different.
      This urged us to perform in-depth analyses of both structure ensembles and the
      deposited experimental data, the results of which clearly identify one of the two
      models as largely incorrect. Next, we analyzed the quality of a large set of
      recent NMR-derived structure ensembles originating from both structural genomics
      projects and individual structure determination groups. Unfortunately, a visual
      inspection of structures exhibiting lower quality scores than DLC2A reveals that
      the seriously flawed DLC2A structure is not an isolated incident. Overall, our
      results illustrate that the quality of NMR structures cannot be reliably
      evaluated using only traditional experimental input data and overall quality
      indicators as a reference and clearly demonstrate the urgent need for a tight
      integration of more sophisticated structure validation tools in NMR structure
      determination projects. In contrast to common methodologies where structures are
      typically evaluated as a whole, such tools should preferentially operate on a per
      residue basis.

PMID- 16462940
TI  - Genetic and genomic analysis of a fat mass trait with complex inheritance reveals
      marked sex specificity.
AB  - The integration of expression profiling with linkage analysis has increasingly
      been used to identify genes underlying complex phenotypes. The effects of gender
      on the regulation of many physiological traits are well documented; however,
      "genetical genomic" analyses have not yet addressed the degree to which their
      conclusions are affected by sex. We constructed and densely genotyped a large F2
      intercross derived from the inbred mouse strains C57BL/6J and C3H/HeJ on an
      apolipoprotein E null (ApoE-/-) background. This BXH.ApoE-/- population
      recapitulates several "metabolic syndrome" phenotypes. The cross consists of 334
      animals of both sexes, allowing us to specifically test for the dependence of
      linkage on sex. We detected several thousand liver gene expression quantitative
      trait loci, a significant proportion of which are sex-biased. We used these
      analyses to dissect the genetics of gonadal fat mass, a complex trait with sex
      specific regulation. We present evidence for a remarkably high degree of sex
      dependence on both the cis and trans regulation of gene expression. We
      demonstrate how these analyses can be applied to the study of the genetics
      underlying gonadal fat mass, a complex trait showing significantly female-biased
      heritability. These data have implications on the potential effects of sex on the
      genetic regulation of other complex traits.

PMID- 16462941
TI  - A link between meiotic prophase progression and crossover control.
AB  - During meiosis, most organisms ensure that homologous chromosomes undergo at
      least one exchange of DNA, or crossover, to link chromosomes together and
      accomplish proper segregation. How each chromosome receives a minimum of one
      crossover is unknown. During early meiosis in Caenorhabditis elegans and many
      other species, chromosomes adopt a polarized organization within the nucleus,
      which normally disappears upon completion of homolog synapsis. Mutations that
      impair synapsis even between a single pair of chromosomes in C. elegans delay
      this nuclear reorganization. We quantified this delay by developing a
      classification scheme for discrete stages of meiosis. Immunofluorescence
      localization of RAD-51 protein revealed that delayed meiotic cells also contained
      persistent recombination intermediates. Through genetic analysis, we found that
      this cytological delay in meiotic progression requires double-strand breaks and
      the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5.
      Failure of X chromosome synapsis also resulted in impaired crossover control on
      autosomes, which may result from greater numbers and persistence of recombination
      intermediates in the delayed nuclei. We conclude that maturation of recombination
      events on chromosomes promotes meiotic progression, and is coupled to the
      regulation of crossover number and placement. Our results have broad implications
      for the interpretation of meiotic mutants, as we have shown that asynapsis of a
      single chromosome pair can exert global effects on meiotic progression and
      recombination frequency.

PMID- 16462942
TI  - Targeting determinants of dosage compensation in Drosophila.
AB  - The dosage compensation complex (DCC) in Drosophila melanogaster is responsible
      for up-regulating transcription from the single male X chromosome to equal the
      transcription from the two X chromosomes in females. Visualization of the DCC, a
      large ribonucleoprotein complex, on male larval polytene chromosomes reveals that
      the complex binds selectively to many interbands on the X chromosome. The
      targeting of the DCC is thought to be in part determined by DNA sequences that
      are enriched on the X. So far, lack of knowledge about DCC binding sites has
      prevented the identification of sequence determinants. Only three binding sites
      have been identified to date, but analysis of their DNA sequence did not allow
      the prediction of further binding sites. We have used chromatin
      immunoprecipitation to identify a number of new DCC binding fragments and
      characterized them in vivo by visualizing DCC binding to autosomal insertions of
      these fragments, and we have demonstrated that they possess a wide range of
      potential to recruit the DCC. By varying the in vivo concentration of the DCC, we
      provide evidence that this range of recruitment potential is due to differences
      in affinity of the complex to these sites. We were also able to establish that
      DCC binding to ectopic high-affinity sites can allow nearby low-affinity sites to
      recruit the complex. Using the sequences of the newly identified and previously
      characterized binding fragments, we have uncovered a number of short sequence
      motifs, which in combination may contribute to DCC recruitment. Our findings
      suggest that the DCC is recruited to the X via a number of binding sites of
      decreasing affinities, and that the presence of high- and moderate-affinity sites
      on the X may ensure that lower-affinity sites are occupied in a context-dependent
      manner. Our bioinformatics analysis suggests that DCC binding sites may be
      composed of variable combinations of degenerate motifs.

PMID- 16462945
TI  - Coordination frameworks--where next?
AB  - A personal perspective on the developing field of coordination frameworks, of
      where the challenges currently lie, where the field is heading and where the next
      breakthroughs will be made.

PMID- 16462946
TI  - A photoluminescent six-coordinated zinc(II) complex with hydroxides as axial
      ligands, [Zn(Hhpa)2(OH)2] (Hhpa = 3-hydroxypicolinamide).
AB  - A highly luminescent zinc(II) complex has been prepared using 3
      hydroxypicolinamide; it has a six-coordinated octahedral structure with
      hydroxides as axial ligands in solution.

PMID- 16462944
TI  - Complex genetic interactions in a quantitative trait locus.
AB  - Whether in natural populations or between two unrelated members of a species,
      most phenotypic variation is quantitative. To analyze such quantitative traits,
      one must first map the underlying quantitative trait loci. Next, and far more
      difficult, one must identify the quantitative trait genes (QTGs), characterize
      QTG interactions, and identify the phenotypically relevant polymorphisms to
      determine how QTGs contribute to phenotype. In this work, we analyzed three
      Saccharomyces cerevisiae high-temperature growth (Htg) QTGs (MKT1, END3, and
      RHO2). We observed a high level of genetic interactions among QTGs and strain
      background. Interestingly, while the MKT1 and END3 coding polymorphisms
      contribute to phenotype, it is the RHO2 3'UTR polymorphisms that are
      phenotypically relevant. Reciprocal hemizygosity analysis of the Htg QTGs in
      hybrids between S288c and ten unrelated S. cerevisiae strains reveals that the
      contributions of the Htg QTGs are not conserved in nine other hybrids, which has
      implications for QTG identification by marker-trait association. Our findings
      demonstrate the variety and complexity of QTG contributions to phenotype, the
      impact of genetic background, and the value of quantitative genetic studies in S.
      cerevisiae.

PMID- 16462943
TI  - Sox6 directly silences epsilon globin expression in definitive erythropoiesis.
AB  - Sox6 is a member of the Sox transcription factor family that is defined by the
      conserved high mobility group (HMG) DNA binding domain, first described in the
      testis determining gene, Sry. Previous studies have suggested that Sox6 plays a
      role in the development of the central nervous system, cartilage, and muscle. In
      the Sox6-deficient mouse, p100H, epsilony globin is persistently expressed, and
      increased numbers of nucleated red cells are present in the fetal circulation.
      Transfection assays in GM979 (erythroleukemic) cells define a 36-base pair region
      of the epsilony proximal promoter that is critical for Sox6 mediated repression.
      Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation
      (ChIP) assays demonstrate that Sox6 acts as a repressor by directly binding to
      the epsilony promoter. The normal expression of Sox6 in wild-type fetal liver and
      the ectopic expression of epsilony in p100H homozygous fetal liver demonstrate
      that Sox6 functions in definitive erythropoiesis. The present study shows that
      Sox6 is required for silencing of epsilony globin in definitive erythropoiesis
      and suggests a role for Sox6 in erythroid cell maturation. Thus, Sox6 regulation
      of epsilony globin might provide a novel therapeutical target in the treatment of
      hemoglobinopathies such as sickle cell anemia and thalassemia.

PMID- 16462947
TI  - Two novel halogeno(cyano)argentates with efficient luminescence.
AB  - The reactions of silver(I) cyanide with tetraalkylammonium salts in anhydrous
      tetrahydrofuran (THF) under solvothermal conditions and then diffused with ether
      lead to two novel mixed halogeno(cyano)argentates(I) with efficient luminescence.

PMID- 16462948
TI  - Group 4 complexes of amine bis(phenolate)s and their application for the ring
      opening polymerisation of cyclic esters.
AB  - A series of amine bis(phenolate) ligand precursors and their group 4 metal
      complexes have been prepared, characterised by single-crystal X-ray diffraction,
      and tested for ring opening polymerisation of epsilon-caprolactone.

PMID- 16462949
TI  - Synthesis, structure and hydrosilylation activity of neutral and cationic rare
      earth metal silanolate complexes.
AB  - Rare-earth metal alkyl tri(tert-butoxy)silanolate complexes [Ln{mu,eta2
      OSi(O(t)Bu)3}(CH2SiMe3)2]2 (Ln = Y (1), Tb (2), Lu (3)) were prepared via
      protonolysis of the appropriate tris(alkyl) complex [Ln(CH2SiMe3)3(thf)2] with
      tri(tert-butoxy)silanol in pentane. Crystal structure analysis revealed a
      dinuclear structure for with square pyramidal geometry at the yttrium centre. The
      silanolate ligand coordinates in an eta2-bridging coordination mode giving a 4
      rung truncated ladder and non-crystallographic inversion centre. Addition of two
      equiv. of 12-crown-4 to a pentane solution of 1 or 3 respectively gave
      [Ln{OSi(O(t)Bu)(3)}(CH2SiMe3)2(12-crown-4)].12-crown-4 (Ln = Y (4), Lu (5)).
      Crystal structure analysis of 5 showed a slightly distorted octahedral geometry
      at the lutetium centre. The silanolate ligand adopts an eta(1)-terminal
      coordination mode, whilst the crown ether unit coordinates in an unusual kappa3
      fashion. Reaction of 1-3 with [NEt3H]+[BPh4]- in thf yielded the cationic
      derivatives [Ln{OSi(O(t)Bu)3}(CH2SiMe3)(thf)4]+[BPh4]- (Ln = Y (6), Tb (7) and Lu
      (8)); coordination of crown ether led to compounds of the form
      [Ln{OSi(O(t)Bu)3}(CH2SiMe3)(L)(thf)n]+[BPh4]- (Ln = Y, Lu, L = 12-crown-4, n = 1
      (9,10); Ln = Y, Lu, L = 15-crown-5, n = 0 (11,12)). Reaction of 1 with
      [NMe2PhH]+[B(C6F5)4]-, [Al(CH2SiMe3)3] or BPh3 in thf gave the ion pairs
      [Y{OSi(O(t)Bu)3}(CH2SiMe3)(thf)4]+[A]- ([A]- = [B(C6F5)4]- (13), [Al(CH2SiMe3)4]-
      (14), [BPh3(CH2SiMe3)]- (15)), whilst two equiv. [NMe2PhH]+[BPh4]- with 1 in thf
      produced the dicationic ion triple [Y{OSi(O(t)Bu)3}(thf)6]2+[BPh4]-2 (16).
      Crystal structure analysis revealed that 16 is mononuclear with pentagonal
      bipyramidal geometry at the yttrium centre. The silanolate ligand coordinates in
      an eta(1)-terminal fashion. All diamagnetic compounds have been characterized by
      NMR spectroscopy. 1, 3, 4, 6 and 13 were tested as olefin hydrosilylation pre
      catalysts with a variety of substrates; 1 was found to be highly active in 1
      decene hydrosilylation.

PMID- 16462951
TI  - Heterometallic cluster complexes (RhMo, RhW) containing bridging 1,2-dicarba
      closo-dodecaborane-1,2-dichalocogenolato ligands.
AB  - The 16-electron half-sandwich rhodium complex [Cp*Rh{E2C2(B10H10)}] [Cp* = eta5
      C5Me5, E = S (1a), Se (1b)] [Cp*Rh{E2C2(B10H10)} = eta5
      pentamethylcyclopentadienyl[1,2-dicarba-closo-dodecaborane(12)
      dichalcogenolato]rhodium] reacted with Mo(CO)3(py)3 in the presence of BF3.Et2O
      in THF solution to afford the {Cp*Rh[E2C2(B10H10)]}2Mo(CO)2 (E = S (3a); Se
      (3b)), {Cp*Rh[S2C2(B10H10)]}{Mo(CO)2[S2C2(B10H10)]} (4). The voluminous di-tert
      butyl substituted Cp half-sandwich rhodium complex [Cp'Rh{E2C2(B10H10)}] [E = S
      (2a), Se (2b)] [CpRh{E2C2(B10H10)} = eta5-(1,3-di(tert-butyl)cyclopentadienyl
      [1,2-dicarba-closo-dodecaborane(12)-dichalcogenolato]rhodium) reacted with
      W(CO)3(py)3 in the presence of BF3.Et2O in THF solution to give the
      {Cp'Rh[S2C2(B10H10)]}{W(CO)2[S2C2(B10H10)]} (5) and {Cp'Rh[Se2C2(B10H10)]}(mu
      CO)[W(CO)3] (6), respectively. The complexes have been fully characterized by IR
      and NMR spectroscopy as well as by elemental analyses. The X-ray crystal
      structures of the complexes 3-6 are reported.

PMID- 16462952
TI  - Reactions between a sodium amide Na[N(SiMe3)R1] (R1 = SiMe3, SiMe2Ph or But) and
      a cyanoalkane RCN (R = Ad or Bu(t)).
AB  - Reactions between sodium amides Na[N(SiMe3)R1] [R1 = SiMe3 (1), SiMe2Ph (2) or
      But (3)] and cyanoalkanes RCN (R = Ad or But) were investigated. In each case the
      nitrile adduct [Na{mu-N(SiMe3)2}(NCR)]2 [R = Ad (1a) or But (1b)], trans-[Na{mu
      N(SiMe3)(SiMe2Ph)}(NCR)]2 [R = Ad (2a) or But (2b)], [(Na{mu
      N(SiMe3)But})3(NCAd)3] (3a) or [(Na{mu-N(SiMe3)But})3(NCBut)n] [n = 3 (3b) or 2
      (3c)] was isolated. The reaction of complexes 3a or 3b with benzene afforded the
      ketimido complex [Na{mu-N=C(Ad)(Ph)}]6.2C6H6 (4a) or [Na{mu-N=C(But)(Ph)}]6 (4b);
      the former was also prepared in more conventional fashion from NaPh and AdCN. The
      synthesis and structure of an analogue of complex 1a, [Li{mu-N(SiMe3)2}(NCAd)]2
      (5a), is also presented. The compounds 1a, 1b, 2a, 2b, 3, 3b, 4a, 4b and 5a were
      characterised by X-ray diffraction.

PMID- 16462950
TI  - Supramolecular architectures assembled by the interaction of purine nucleobases
      with metal-oxalato frameworks. Non-covalent stabilization of the 7H-adenine
      tautomer in the solid-state.
AB  - The synthesis, crystal structure and variable-temperature magnetic measurements
      of the compounds [Mn(mu-ox)(H2O)(7H-pur-kappaN9)]n (1), {[Mn(mu-ox)(H2O)2].(7H
      ade).(H2O)}n (2) and {[Cu(mu-ox)(H2O)(7H-ade-kappaN9)][Cu(mu-ox)(mu-H2O)(7H-ade
      kappaN9)]. approximately 10/3H2O}n (3), (where ox: oxalato dianion, pur: purine,
      and ade: adenine) are reported. Compounds 1and 2 contain one-dimensional chains
      in which manganese(II) atoms are bridged by bis-bidentate oxalato ligands. The
      distorted octahedral geometry around each metal centre is completed in compound 1
      by one water molecule and the imidazole N9 donor site of the purine ligand, which
      is a rare example of direct binding between the Mn(II) ion and the N donor site
      of an isolated nucleobase. Unlike 1, the adenine moiety in compound 2 is not
      bonded to manganese atoms and the metal coordination polyhedron is filled by two
      water molecules in a cis-arrangement. Its crystal building is constructed from pi
      stacked layers of Watson-Crick hydrogen-bonded adenine...(H2O2)...adenine
      aggregates and zig-zag Mn(II)-oxalato chains held together by means of a strong
      network of hydrogen bonding interactions. The nucleobase exists in the lattice as
      the 7H-adenine tautomer which represents an unprecedented solid-state
      characterization of this minor tautomer as free molecule (without metal
      coordination) stabilized through non-covalent interactions. Compound consists of
      two slightly different [Cu(ox)(H2O)(7H-ade-kappaN9)] units in which the
      nucleobase coordinates through the imidazole N9 atom. The planar complex entities
      are parallel stacked and joined by means of long Cu-O bonds involving oxygen
      atoms from the oxalato and the aqua ligands, giving one-dimensional chains with a
      [4 + 1] square-planar pyramidal and a [4 + 2] octahedral coordination around the
      metal centre, respectively. Self-assembled process of compound 3 is further
      driven by an in-plane network of hydrogen bonding interactions to generate a
      porous 3D structure containing parallel channels filled by guest water molecules.
      Variable-temperature magnetic susceptibility measurements of all the complexes
      show the occurrence of antiferromagnetic interactions between the paramagnetic
      centres. DFT calculations have been performed to check the influence of packing
      in the stability of the 7H-amino tautomer of 2 and in the complex geometry of 3.

PMID- 16462953
TI  - Comparison of structurally analogous Zn2, Co2, and Mg2 catalysts for the
      polymerization of cyclic esters.
AB  - Three dimetallic monoethoxide complexes supported by a binucleating phenoxide
      ligand, LM2Cl2OEt (M = Zn, Co, or Mg), were prepared and shown by X-ray
      crystallography to be structurally analogous. Comparative studies of their cyclic
      ester polymerization reactivity revealed different trends for reactions with
      epsilon-caprolactone and lactide, however, implicating complicated effects of
      metal ion variation in these polymerizations.

PMID- 16462954
TI  - Synthesis, characterisation, reactivity and in vitro antiamoebic activity of
      hydrazone based oxovanadium(IV), oxovanadium(V) and mu
      bis(oxo)bis{oxovanadium(V)} complexes.
AB  - Binuclear, mu-bis(oxo)bis{oxovanadium(V)} complexes [(VOL)2(mu-O)2](2 and
      7)(where HL are the hydrazones Hacpy-nah I or Hacpy-fah II; acpy = 2
      acetylpyridine, nah = nicotinic acid hydrazide and fah = 2-furoic acid hydrazide)
      were prepared by the reaction of [VO(acac)2] and the ligands in methanol followed
      by aerial oxidation. The paramagnetic intermediate complexes [VO(acac)(acpy
      nah)](1) and [VO(acac)(acpy-fah)](6) have also been isolated. Treatment of
      [VO(acac)(acpy-nah)] and [VO(acac)(acpy-fah)] with aqueous H2O2 yields the
      oxoperoxovanadium(V) complexes [VO(O2)(acpy-nah)](3) and [VO(O2)(acpy-fah)](8).
      In the presence of catechol (H2cat) or benzohydroxamic acid (H2bha), 1 and 6 give
      the mixed chelate complexes [VO(cat)L](HL =I: 4, HL =II: 9) or [VO(bha)L](HL =I:
      5, HL =II: 10). Complexes 4, 5, 9 and 10 slowly convert to the corresponding oxo
      mu-oxo species 2 and 7 in DMF solution. Ascorbic acid enhances this conversion
      under aerobic conditions, possibly through reduction of these complexes with
      concomitant removal of coordinated catecholate or benzohydroxamate. Acidification
      of 7 with HCl dissolved in methanol afforded a hydroxo(oxo) complex. The crystal
      and molecular structure of 2.1.5H2O has been determined, and the structure of 7
      re-determined, by single crystal X-ray diffraction. Both of these binuclear
      complexes contain the uncommon asymmetrical {VO(mu-O)}2 diamond core. The in
      vitro tests of the antiamoebic activity of ligands I and II and their binuclear
      complexes 2 and 7 against the protozoan parasite Entamoeba histolytica show that
      the ligands have no amoebicidal activity while their vanadium complexes 2 and 7
      display more effective amoebicidal activity than the most commonly used drug
      metronidazole (IC50 values are 1.68 and 0.45 microM, respectively vs 1.81 microM
      for metronidazole). Complexes 2 and 7 catalyse the oxidation of styrene and ethyl
      benzene effectively. Oxidation of styrene, using H2O2 as an oxidant, gives
      styrene epoxide, 2-phenylacetaldehyde, benzaldehyde, benzoic acid and 1-phenyl
      ethane-1,2-diol, while ethyl benzene yields benzyl alcohol, benzaldehyde and 1
      phenyl-ethane-1,2-diol.

PMID- 16462955
TI  - Exchange coupling across the cyanide bridge: structural and DFT interpretation of
      the magnetic properties of a binuclear chromium(III) complex.
AB  - The reaction of [Cr(CN)6]3- with a mixture of trans-[Cr(cyclam)(OH)2]Cl,
      [Cr(cyclam)(OH)Cl]Cl and [Cr(cyclam)Cl2]Cl affords the cyanide bridged dimer,
      trans-[HO-Cr(cyclam)-NC-Cr(CN)5]-. The tetraphenylphosphonium salt of the anion
      crystallizes in space group P2(1)/n and shows a bent arrangement of the Cr1-CN
      Cr2 unit with the Cr1-CN bond angle at 166.9 degrees and CN-Cr2 at 160.32 degrees
      . The Cr2-O bond, trans to the hexacyanide fragment, is very short at 1.902 A.
      Two dimers are held together by two hydrogen bonds connecting the Cr2-OH group of
      each dimer with one of the NH groups of the cyclam ligand of an adjacent
      molecule, leading to an almost linear configuration. These dimers of dimers get
      packed parallel to each other, generating layers separated by the
      tetraphenylphosphonium cations. Four of the cyanide groups of the anion are
      engaged in H-bonds with the four water molecules present in the structure or with
      a NH group of the macrocycle of an adjacent molecule. From magnetic
      susceptibility measurements, the dimer was found to exhibit antiferromagnetic
      interaction between the Cr(III) centers with J=-16 cm(-1)(H=-2JS(A)S(B)).
      Structural and magnetic parameters have been calculated by density functional
      theoretical methods at the B3LYP level. The exchange coupling constant, J,
      calculated for the dimer at the X-ray geometry is -23.2 cm(-1) which is in
      excellent agreement with the experimental value.

PMID- 16462956
TI  - Kinetics of the light-driven aqueous autoxidation of sulfur(IV) in the absence
      and presence of iron(II).
AB  - The photochemical autoxidation of aqueous, acidic sulfur(IV) solutions was
      studied in the absence and presence of iron(II) by a newly introduced technique
      using a diode-array spectrophotometer, in which the same light source is used to
      drive and detect the reaction. Based on detailed kinetic and stoichiometric data
      sets, a non-chain mechanism is proposed for the autoxidation of sulfur(IV). In
      this mechanism, excited hydrated sulfur dioxide, *H2O.SO2, first reacts with O2
      to form peroxomonosulfate ion, HSO5-, which rapidly oxidizes another H2O.SO2 to
      give hydrogensulfate ion as a final product. In the presence of iron(II), the
      formation of iron(III) was detected, which can be interpreted through the
      simultaneous contribution of two additional pathways: some of the HSO5- formed
      oxidizes iron(II) instead of sulfur(iv), and *H2O.SO2 also reacts directly with
      iron(II) to yield iron(III). This mechanism provides a sufficient quantitative
      interpretation of all experimental observations.

PMID- 16462957
TI  - Syntheses and magnetic properties of Cu(II)(hfac)2 and Mn(II)(hfac)2 complexes of
      4-pyridyl-substituted thioaminyl radicals.
AB  - Two types of Cu(II)(hfac)2 and Mn(II)(hfac)2 complexes of N-(4-pyridylthio)-4
      ethoxycarbonyl-2,6-bis(4-chlorophenyl)phenylaminyl (1) and N-(4-pyridylthio)
      2,4,6-tris(4-chlorophenyl)phenylaminyl (2) were prepared and their X-ray
      crystallographic and magnetic studies were performed. Mixtures of Cu(II)(hfac)2
      and 1 and Mn(II)(hfac)2 and 2 in anhydrous heptane-benzene solution gave 1 : 2
      complexes of M(II)(hfac)2 (M = Cu, Mn) and 1 or 2 in 73-75% yields. For
      Cu(II)(hfac)2(1)2 and Mn(II)(hfac)2(2)2 X-ray crystallographic analyses were
      successfully performed. The magnetic behaviors for the two metal complexes were
      investigated with a SQUID magnetometer. The analyses for the chimolTvs. T plots
      of Cu(II)(hfac)2(1)2 were carried out by the numerical diagonalization of the
      Heisenberg Hamiltonian matrix (4096 x 4096 matrix) for the four repeating units
      of the complex (12-spin system). The exchange interaction between the copper(II)
      ion and the thioaminyl radicals is ferromagnetic (J1/kB = +28 K) and the
      interactions between the complexes is antiferromagnetic (J2/kB = -13 K). The
      magnetic behavior of Mn(II)(hfac)2(2)2 complexes is well analyzed with the
      theoretical equation of a 1/2-5/2-1/2 three-spin system taking the intermolecular
      interaction (theta) into account. The exchange interaction between the Mn(II) ion
      and the thioaminyl radicals is antiferromagnetic (J/kB = -4.2 K) and theta = -1.0
      K. These magnetic behaviors could be well explained in terms of their crystal
      structures.

PMID- 16462958
TI  - Co-complexes of ortho-dilithiated thiophenol or 2-trimethylsilylthiophenol with
      lithiated TMEDA molecules: synthesis, crystal structures and theoretical studies
      (TMEDA = N,N,N',N'-tetramethylethylenediamine).
AB  - When an excess of nBuLi was used in the ortho-dilithiation of thiophenol or 2
      trimethylsilylthiophenol in the presence of TMEDA (TMEDA = N,N,N',N'
      tetramethylethylenediamine), deprotonation of TMEDA occurred and crystals of
      [Li3{(2-S-C6H4)(CH2MeNCH2CH2NMe2)(TMEDA)}]2 (1) or [Li4{(2-S-3-SiMe3
      C6H3)(CH2MeNCH2CH2NMe2)2(TMEDA)}] (2) were obtained. Molecular orbital
      calculations on gas-phase 1 and 2 at the DFT B3LYP/6-31G(d) level reproduce the
      experimental structures fairly well. In spite of the short Li...Li distances,
      total electron density representations do not support the existence of Li...Li
      interactions.

PMID- 16462959
TI  - [Molecular detection of Mycoplasma genitalium in men and pregnant women].
AB  - Mycoplasma genitalium is an opportunistic pathogen of the genital tract. It has
      been implicated as an etiological agent of urethritis in men and cervicitis and
      pelvic inflammatory disease (PID) in women. The aim of this study was to
      determine the prevalence of Mycoplasma genitalium in male urethritis and in
      vaginal specimens of pregnant women. Urethral specimens obtained from 37 men
      presenting with urethritis and vaginal specimens from 50 consecutive pregnant
      women were tested for the presence of M. genitalium by polymerase chain reaction
      (PCR). The urethral specimens were also examined for the presence of Neisseria
      gonorrhoeae, Chlamydia trachomatis and Ureaplasma sp whereas the vaginal
      microbiota and the presence of genital mycoplasma were investigated in the
      vaginal specimens. Twenty three cases were classified as nongonococcal urethritis
      (NGU) and 14 as gonorrheal disease. M. genitalium was detected in 3 of 23
      (13.04%) men with NGU; in two cases with Ureaplasma sp, and in one patient as the
      unique agent. C. trachomatis was found in 7 patients with NGU and in one patient
      with gonorrhea. Ureaplasma sp was isolated in 13 (35.1%) patients, 8 cases of NGU
      and in 5 patients with gonorrhea. The organism was also detected in 6 (15%) of 40
      women; in 5 cases in the presence of a normal microbiota (Nugent score 0-3), and
      an in one case in the presence of bacterial vaginosis. Ureaplasma spp was
      isolated in the 6 positive specimens. This study indicates that M. genitalium can
      be detected in urethral specimens of some cases of NGU as well as in the lower
      genital tract of pregnant women in the presence of a normal vaginal microbiota.

PMID- 16462960
TI  - [Guidelines for management of animal bites].
AB  - Bites caused by pets or free living animal, including the so called exotic ones
      are a common cause of medical care request, although its real dimension has not
      been well defined in the local setting. This paper reviews the epidemiology of
      the topic placing emphasis in the initial approach and recommendations for the
      management of dog and cat bites. Due to increasing ownership or contact with
      other animals, management of bites from hamsters, mice, ferrets, rabbits, prairie
      dogs, monkeys, bats, lizards and bird bites is also discussed.

PMID- 16462961
TI  - [Clinical features and costs of rotavirus gastroenteritis in infants: community
      versus nosocomialy acquired infection].
AB  - This is a prospective 12 month (July 2003-June 2004) cohort study in one large
      tertiary hospital of Santiago, Chile aimed to describe clinic features and
      calculate the direct costs of hospitalization associated to community-acquired (n
      = 78) and nosocomially-acquired (n = 52) rotavirus infection. A gastroenteritis
      severity score after Rennels 1996, (0 to 17 points) was applied and costs where
      calculated based on those assigned by the Chilean National Funds for Health
      (FONASA). Severe gastroenteritis manifested by a score > 14 occurred in 26.9% and
      9.6% of community and nosocomially-acquired cases respectively (p < 0.015). The
      former had lower bicarbonate levels (p < 0.001), and required more volume
      expansion compared to the latter (p < 0.023). The average cost was US 277 per
      case for community acquired rotavirus and US 268 for nosocomial infection. In
      this hospital the cost of nosocomial rotavirus infection was approximately 13,900
      US dollars for a 12 month period. These results should stimulate the
      implementation of active prevention and control programs.

PMID- 16462962
TI  - [Policies for influenza control in Chile].
AB  - Influenza control is based in two main components: a surveillance system and
      vaccination. In both aspects Chile has conquered high internacional standards and
      can exhibit the best results in the Region, obtaining a significant reduction in
      mortality attributable to influenza and pneumonia as vaccine coverage has
      increased over 11% of the total population. Pandemic influenza menace is
      permanent and obliges national authorities to prepare special strategies to face
      it.

PMID- 16462963
TI  - [Angiographic catheter reuse at the Hemodynamic Department of a public hospital
      in Chile].
AB  - This article presents the results of a study conducted in 421 patients who
      underwent invasive procedures utilizing catheters for diagnosis and treatment at
      the Hemodynamic Department of a Public Hospital during the period between July
      and December 2003. The goal of this study was to determine the existence of risks
      in the reuse of disposable angiographic catheters. This study was designed as an
      observational prospective cohort follow up. From the sample studied, 63.4% were
      males with average age of 64 years. Co-morbidities were diabetes mellitus and
      obesity in 27 and 24% respectively. Eighty two percent of the procedures were
      diagnostic and reused catheters were used in 74% of all procedures. Local
      infection or systemic pyrogenic reaction was observed in 4.3% patients, however
      there were no significant differences in any of the variables studied, between
      the group in which reused catheters were used and the group with new catheters (p
      < 0.05).

PMID- 16462965
TI  - [Kingella kingae].

PMID- 16462964
TI  - [Invasive infections caused by Haemophilus influenzae type b after the
      institution of the conjugated vaccine on the expanded programm on immunization in
      Chile].
AB  - After almost a decade since the introduction of Haemophilus influenzae type b
      (Hib) conjugate vaccines in Chile (in a 2-4-6 month schedule), Hib invasive
      infections have dramatically decreased, albeit they remain to occasionally
      produce disease in pediatric patients. We report our experience with children
      whom developed Hib invasive disease in children since 2000 to 2004. Medical
      records of children with Hib were reviewed in order to describe the epidemiology,
      main clinical and laboratory findings, management and complications. Twenty three
      patients (17 male), between 1 and 71 months (median 30 months) were identified:
      pneumonia (7), meningitis (4), pleuropneumonia (2), empyema (2), sepsis (2),
      cellulitis (2), meningitis and pleuropneumonia (1), purpura fulminans (1),
      miositis (1) and epiglottitis (1). No deaths were observed and four patients
      presented severe sequelae at hospital discharge. Twenty patients were considered
      vaccine failures. Hib remains as a sporadic cause of severe disease in Chile and
      thus for physicians should still keep it in mind. Case analysis and active
      surveillance are necessary to monitor the current immunization regimen.

PMID- 16462966
TI  - [Varicella vaccine].
AB  - Varicella and herpes zoster represent a significant public health problem. Safe
      and highly effective varicella vaccines against severe and moderate varicella are
      currently available. Vaccine efficacy is lower and more variable against mild
      disease and several risk factors have been associated with mild breakthrough
      disease. Experts are currently discussing the need for a second vaccine dose.
      Universal varicella vaccination has been highly effective in reducing morbidity
      and hospitalizations due to varicella, a strategy that has proven to be cost
      effective in many regions when the societal-perspective is considered in the
      analysis. Recent data suggests that varicella vaccination may be associated with
      an increased incidence of herpes zoster in the elderly. Immunity conferred by
      varicella vaccination seems to be longlasting but a continued evaluation is
      needed in order to asses the effect of the changing epidemiology associated with
      universal immunization.

PMID- 16462967
TI  - [Pertussis chemoprophylaxis: a sterile effort?].
AB  - Pertussis chemoprophylaxis is indicated for contacts at risk of death or of
      severe complications if infected with Bordetella pertussis; e.g. neonates and
      infants <or= 12 months of age, elderly individuals, individuals with cardiac
      and/or respiratory insufficiency, and pregnant women during their third trimester
      of pregnancy (in order to protect their offspring). Available evidence indicates
      that PChP is effective and thus recommendable for high risk household contacts
      within a 21 day window after the beginning of symptoms of the index case, and if
      no secondary case has occurred, recommendation that may be extended to high risk
      individuals that co-habit with an index case at hospital, daycare centers or
      institutionalized elderly people. Bordetella pertussis can be transmitted by
      respiratory droplets that can travel further than the critical distance of 1.5
      meters. This long distance transmissibility is relevant when considering who
      should receive prophylaxis during a nosocomial outbreak. Current evidence
      supports the use of macrolides and azalides for Pertussis chemoprophylaxis; seven
      days of erythromycin or clarithromycin and five days of azythromycin are
      sufficient to eradicate B. pertussis.

PMID- 16462968
TI  - [Invasive multisystemic aspergillosis in an immunocompetent child: case report].
AB  - Invasive aspergillosis is a severe disease, with an increased incidence in last
      decades. It occurs mainly in immunocompromised patients and rarely affects
      immunocompetent hosts. We describe a previously healthy 8 -year-old boy who
      acquired an invasive aspergillosis of abdominal origin associated with an opened
      laparotomy; within three weeks the patient progressed to a multiple organic
      failure syndrome and died despite amphotericin B deoxycolate plus voriconazole
      treatment and aggressive surgical debridement. Necropsy revealed multiple
      parenchyma involvement with characteristic findings of angioinvasive
      aspergillosis. Invasive aspergillosis must be considered an emergent infection in
      critical pediatric patients, including previously immunocompetent hosts; it is
      associated with high mortality despite adequate and opportune therapy.

PMID- 16462969
TI  - [Subdural empyema secondary to sinusitis].
AB  - Subdural empyema is a rare complication of sinusitis in children. Its clinical
      presentation represents a neurosurgical emergency and as a scarcely recognized
      entity a delayed diagnosis rapidly increases its fatal prognosis. We report the
      clinical and radiological course of an adolescent with a subdural empyema
      secondary to sinusitis. Clinical and radiological features, laboratory findings
      and outcome of this condition are discussed based in a review of previously
      reported cases.

PMID- 16462970
TI  - [The strangling of children (diphtheria) in Spain (16th and 17th Centuries)].

PMID- 16462972
TI  - Putting evidence into practice in low-resource settings.

PMID- 16462973
TI  - The need for development assistance for health in the eastern European Region.

PMID- 16462974
TI  - Policy and partnership for health promotion--addressing the determinants of
      health.

PMID- 16462975
TI  - Polypill holds promise for people with chronic disease.

PMID- 16462976
TI  - Best defence against avian flu is to fight the virus in Asia.

PMID- 16462977
TI  - Quake victims reach help too late to save crushed limbs.

PMID- 16462978
TI  - Growing awareness of skin disease starts flurry of initiatives.

PMID- 16462979
TI  - Lessons from the tsunami.

PMID- 16462981
TI  - Evidence-based reproductive health care in Cameroon: population-based study of
      awareness, use and barriers.
AB  - OBJECTIVE: To estimate the prevalence of awareness and use of evidence-based
      reproductive health interventions and to describe the barriers associated with
      the use of evidence-based interventions among health providers in north-west
      Cameroon. METHODS: In February 2004, a population-based descriptive study of the
      awareness and use of 13 evidence-based interventions targeted health workers
      providing reproductive health care. Their awareness and use of a composite of
      four vital interventions was also evaluated. These were peripartum use of
      antiretrovirals to prevent transmission of HIV, antenatal corticosteroid
      administration, magnesium sulfate prophylaxis and active management of placental
      delivery with uterotonics. In-depth interviews with key informants were conducted
      as part of a qualitative substudy to discover the barriers to the use of evidence
      based interventions. FINDINGS: Overall, 91.4% (328/359) of reproductive health
      workers were surveyed. Their awareness of evidence-based interventions varied
      from 29% for the use of antenatal corticosteroids to 97% for the use of iron and
      folic acid supplementation during pregnancy. Their use of these interventions
      ranged from 10.2% for antenatal corticosteroids to 94.8% for iron and folic acid
      supplementation. Only 50/322 (15.5%; 95% confidence interval (CI)=11.8-20.0) of
      health workers were aware of all four vital interventions, and only 12/312 (3.8%;
      95% CI=2.0- 6.6) reported using all of them regularly. A total of 26 key
      informants participated in the qualitative substudy. A deficiency in the
      education and training of health workers, especially a lack of continuing
      education, was commonly identified as the most important barrier to their
      awareness of evidence-based practices. A lack of awareness and a lack of supplies
      and materials were the main barriers to practice. CONCLUSION: The awareness and
      practice of important evidence-based reproductive health interventions were less
      than optimal. To improve maternal and perinatal outcomes both remedial programmes
      to enhance awareness, including continuing education for health workers, and the
      provision of necessary supplies are needed.

PMID- 16462982
TI  - The epidemiology of trachoma in Eastern Equatoria and Upper Nile States, southern
      Sudan.
AB  - OBJECTIVE: Limited surveys and anecdotal data indicate that trachoma is endemic
      in the states of Eastern Equatoria and Upper Nile in southern Sudan. However, its
      magnitude and geographical distribution are largely unknown. We conducted surveys
      to ascertain the prevalence and geographical distribution of trachoma, and to
      identify targets for control interventions. METHODS: Population-based cross
      sectional surveys were conducted in nine sites in southern Sudan between
      September 2001 and June 2004. Two-stage random cluster sampling with probability
      proportional to size was used to select the sample. Trachoma grading was done
      using the WHO simplified grading system. FINDINGS: A total of 17 016 persons were
      examined, a response rate of 86.1% of the enumerated population. Prevalence of
      signs of active trachoma in children aged 1-9 years was: TF=53.7% (95% confidence
      interval (CI)=52.1-55.3); TI=42.7% (95% CI=41.2-44.2); TF and/or TI=64.1% (95%
      CI=62.5-65.5). Prevalence of trichiasis (TT) in children aged less than 15 years
      was 1.2% (95% CI=0.9-1.4), while TT prevalence in persons aged 15 years and above
      was 9.2% (95% CI=8.6-9.9). Women were more likely to have trichiasis compared to
      men (odds ratio (OR)=1.57; 95% CI=1.34-1.84). Tentative extrapolation to the
      states of Eastern Equatoria and Upper Nile estimates that there is a backlog of
      178,250 (lower and upper bounds=156,027-205,995) persons requiring surgery and
      the entire population, estimated to be over 3.9 million, is in need of the SAFE
      strategy to control blinding trachoma. CONCLUSION: Trachoma is a public health
      problem in all nine of the study sites surveyed. The unusually high prevalence of
      active trachoma and TT in children points to the severity of the problem. There
      is urgent need to implement trachoma control interventions in trachoma endemic
      regions of southern Sudan.

PMID- 16462983
TI  - Mapping the global distribution of trachoma.
AB  - OBJECTIVE: We aimed to summarize and map the existing global population-based
      data on active trachoma and trichiasis. Detailed distribution maps of various
      infectious diseases have proved a valuable tool in their control. Such maps play
      an important role in assessing the magnitude of the problem, defining priority
      areas for control, monitoring changes, and advocacy. Until now, information on
      trachoma prevalence at within country levels has not been systematically
      collated, analysed and reported. METHODS: We gathered the last 18 years' worth of
      reported data on active trachoma in children aged less than 10 years, and the
      last 25 years of reported trichiasis in adults aged 15 years and over from 139
      population-based surveys in 33 countries. We collated these data into one
      database using the "district" (second administrative level) as the standard unit
      of reporting. We used Geographical Information Systems as a database and
      cartographic tool to generate a global map of the prevalence of trachoma and
      trichiasis. FINDINGS: We obtained data on active trachoma and trichiasis from 18
      countries in the WHO African Region, 6 in the Eastern Mediterranean Region, 3 in
      the South-East Asia Region, 3 in the Western Pacific Region and 2 in the Region
      of the Americas. In 23 countries suspected of having endemic trachoma no reliable
      district-level population-based data were available. In China and India, data
      were limited to a few districts. The data highlighted important regional
      differences and marked national variations in prevalence of active trachoma and
      trichiasis. CONCLUSION: This is the first attempt to summarize and map the
      existing population-based data on active trachoma and trichiasis. The lack of
      data in many countries remains an important obstacle to trachoma control efforts.

PMID- 16462984
TI  - Development assistance for health in central and eastern European Region.
AB  - OBJECTIVE: We aimed to quantify development assistance for health to countries of
      central and eastern Europe and the Commonwealth of Independent States (CEE-CIS).
      METHODS: We used the International Development Statistics database of the
      Organisation for Economic Co-operation and Development and the database on
      development assistance for health compiled for the Commission on Macroeconomics
      and Health to quantify health development assistance to the region, compared to
      global and overall development assistance. We based our analysis on standard
      health indicators, including child mortality, life expectancy at birth and health
      expenditures. FINDINGS: Although total development assistance per capita to CEE
      CIS was higher than that for most other regions of the world, development
      assistance for health was very low compared to other countries with similar
      levels of child mortality, life expectancy at birth and national expenditures on
      health. CONCLUSION: The allocation of development assistance for health on a
      global scale seems to be related far more to child mortality rather than adult
      mortality. Countries of CEE-CIS have a high burden of adult morbidity and
      mortality from non-communicable diseases, which does not appear to attract
      proportionate development assistance. Levels of development assistance for health
      should be determined in consideration of the region's particular burden of
      disease.

PMID- 16462985
TI  - Global surveillance for chemical incidents of international public health
      concern.
AB  - OBJECTIVE: In December 2001, an expert consultation convened by WHO identified
      strengthening national and global chemical incident preparedness and response as
      a priority. WHO is working towards this objective by developing a surveillance
      and response system for chemical incidents. This report describes the frequency,
      nature and geographical location of acute chemical incidents of potential
      international concern from August 2002 to December 2003. METHODS: Acute chemical
      incidents were actively identified through several informal (e.g. Internet-based
      resources) and formal (e.g. various networks of organizations) sources and
      assessed against criteria for public health emergencies of international concern
      using the then proposed revised International Health Regulations (IHR). WHO
      regional and country offices were contacted to obtain additional information
      regarding identified incidents. FINDINGS: Altogether, 35 chemical incidents from
      26 countries met one or more of the IHR criteria. The WHO European Region
      accounted for 43% (15/35) of reports. The WHO Regions for Africa, Eastern
      Mediterranean and Western Pacific each accounted for 14% (5/35); South-East Asia
      and the Americas accounted for 9% (3/35) and 6% (2/35), respectively. Twenty
      three (66%) events were identified within 24 hours of their occurrence.
      CONCLUSION: To our knowledge this is the first global surveillance system for
      chemical incidents of potential international concern. Limitations such as
      geographical and language bias associated with the current system are being
      addressed. Nevertheless, the system has shown that it can provide early detection
      of important events, as well as information on the magnitude and geographical
      distribution of such incidents. It can therefore contribute to improving global
      public health preparedness.

PMID- 16462987
TI  - Exploiting the potential of vector control for disease prevention.
AB  - Although vector control has proven highly effective in preventing disease
      transmission, it is not being used to its full potential, thereby depriving
      disadvantaged populations of the benefits of well tried and tested methods.
      Following the discovery of synthetic residual insecticides in the 1940s, large
      scale programmes succeeded in bringing many of the important vector-borne
      diseases under control. By the late 1960s, most vector-borne diseases--with the
      exception of malaria in Africa--were no longer considered to be of primary public
      health importance. The result was that control programmes lapsed, resources
      dwindled, and specialists in vector control disappeared from public health units.
      Within two decades, many important vector-borne diseases had re-emerged or spread
      to new areas. The time has come to restore vector control to its key role in the
      prevention of disease transmission, albeit with an increased emphasis on multiple
      measures, whether pesticide-based or involving environmental modification, and
      with a strengthened managerial and operational capacity. Integrated vector
      management provides a sound conceptual framework for deployment of cost-effective
      and sustainable methods of vector control. This approach allows for full
      consideration of the complex determinants of disease transmission, including
      local disease ecology, the role of human activity in increasing risks of disease
      transmission, and the socioeconomic conditions of affected communities.

PMID- 16462986
TI  - Integration of basic dermatological care into primary health care services in
      Mali.
AB  - OBJECTIVE: To evaluate, in a developing country, the effect of a short training
      programme for general health care workers on the management of common skin
      diseases--a neglected component of primary health care in such regions. METHODS:
      We provided a one-day training programme on the management of the skin diseases
      to 400 health care workers who worked in primary health care centres in the
      Bamako area. We evaluated their knowledge and practice before and after training.
      FINDINGS: Before training, knowledge about skin diseases often was poor and
      practice inadequate. We found a marked improvement in both parameters after
      training. We analysed the registers of primary health care centres and found that
      the proportion of patients who presented with skin diseases who benefited from a
      clear diagnosis and appropriate treatment increased from 42% before the training
      to 81% after; this was associated with a 25% reduction in prescription costs.
      Improved levels of knowledge and practice persisted for up to 18 months after
      training. CONCLUSIONS: The training programme markedly improved the basic
      dermatological abilities of the health care workers targeted. Specific training
      may be a reasonable solution to a neglected component of primary health care in
      many developing countries.

PMID- 16462988
TI  - Priorities for research to take forward the health equity policy agenda.
AB  - Despite impressive improvements in aggregate indicators of health globally over
      the past few decades, health inequities between and within countries have
      persisted, and in many regions and countries are widening. Our recommendations
      regarding research priorities for health equity are based on an assessment of
      what information is required to gain an understanding of how to make substantial
      reductions in health inequities. We recommend that highest priority be given to
      research in five general areas: (1) global factors and processes that affect
      health equity and/or constrain what countries can do to address health inequities
      within their own borders; (2) societal and political structures and relationships
      that differentially affect people's chances of being healthy within a given
      society; (3) interrelationships between factors at the individual level and
      within the social context that increase or decrease the likelihood of achieving
      and maintaining good health; (4) characteristics of the health care system that
      influence health equity and (5) effective policy interventions to reduce health
      inequity in the first four areas.

PMID- 16462989
TI  - How gender (in)sensitive are the gender-related indices?

PMID- 16462991
TI  - [World health survey in Brazil, 2003].

PMID- 16462992
TI  - Healthy life expectancy in Brazil: applying the Sullivan method.
AB  - The objective of this study is to present the method proposed by Sullivan and to
      estimate the healthy life expectancy using different measures of state of health,
      based on information from the World Health Survey carried out in Brazil in 2003.
      By combining information on mortality and morbidity into a unique indicator,
      simple to calculate and easy to interpret, the Sullivan method is currently the
      one most commonly used for estimating healthy life expectancy. The results show
      higher number of healthy years lost if there is a long-term disease or disability
      that limits daily activities, regardless of the difficulty in performing such
      activities or the severity of the functional limitations. The two measures of
      healthy life expectancy adjusted by the severity of functional limitation show
      results very similar to estimates based on the perception of state of health,
      especially in advanced age. It was also observed, for all measures used, that the
      proportion of healthy years lost increases significantly with age and that,
      although females have higher life expectancy than males, they live proportionally
      less years in good health.

PMID- 16462993
TI  - Fruit and vegetable intake by Brazilian adults, 2003.
AB  - This study estimated indicators of fruit and vegetable intake by Brazilian adults
      and examined the influence of demographic and socioeconomic variables on the
      consumption of these foods. We used the following indicators: daily fruit intake,
      daily vegetable intake, and daily consumption of five or more servings of fruits
      and vegetables per day. Only 41.0% of adults reported daily fruit intake, while
      30.0% reported daily vegetable intake. Fruit and vegetable intake was more common
      in urban as compared to rural areas and increased in both genders with age,
      schooling, and number of household goods. We conclude that initiatives to promote
      fruit and vegetable consumption are necessary for the country as a whole, but
      special attention should be given to younger individuals, males, rural
      communities, and groups with less schooling and lower income.

PMID- 16462994
TI  - The World Health Survey: a report on the field experience in Brazil.
AB  - This article reports on the field experience with the World Health Survey in
      Brazil with the aim of collaborating in the development and enhancement of the
      methodology and analyzing interview questions based on the interviewers'
      experience. The authors comment on the field experience and application of the
      questionnaire, based on reports by regional coordinators and interviewers, in
      order to shed light on the context in which the interviews took place. The
      article reports on how the respondents grasped and interpreted the questionnaire.
      The authors propose improvements in interviewer training and simple interview
      reporting measures aimed at improved logistics with such nationwide survey
      instruments.

PMID- 16462995
TI  - State of animus among Brazilians: influence of socioeconomic context?
AB  - Preliminary results of the World Health Survey, conducted in Brazil in 2003,
      indicate a high frequency of self-perceived problems related to state of animus.
      The main objective of the present study is to investigate the hypothesis that
      material deprivation and job insecurity are important determinants of self
      reported mental problems, such as feelings of depression and anxiety. Analysis of
      factors associated with self-perceived problems related to state of animus was
      performed with multivariate logistic regression models. Among females, key
      factors associated with feelings of depression and anxiety were level of
      education and unemployment after controlling for age, presence of long duration
      disease or disability and of body injury limiting everyday activities. Among
      males, feelings of depression were most strongly associated with unemployment,
      followed by poverty (as measured by a household asset indicator), with being
      married (or cohabiting) showed a protector effect. With regard to severe feelings
      of anxiety, only unemployment contributed significantly. These findings highlight
      the influence of social and economic contexts, beyond strictly individual
      characteristics, on the health of Brazilians.

PMID- 16462996
TI  - Socio-demographic characteristics, treatment coverage, and self-rated health of
      individuals who reported six chronic diseases in Brazil, 2003.
AB  - The Brazilian World Health Survey, carried out in 2003, included questions about
      diagnosis of six chronic diseases: arthritis, angina, asthma, depression,
      schizophrenia and diabetes mellitus. The probabilistic sample of 5,000 adults was
      selected in 250 census tracts. We analyzed the socio-demographic profile, the
      coverage of treatment, and self-rated health of the individuals that reported
      diagnosis of one of these diseases. To control for age and sex, logistic
      regression models were used. Among the 5,000 participants, 39.1% reported medical
      diagnosis of at least one of the six diseases. Depression was the most prevalent
      (19.2%), followed by asthma (12.0%), arthritis (10.5%), angina (6.7%), diabetes
      (6.2%) and schizophrenia (1.7%). Significant differences by age were found for
      all diseases, except for asthma. All diseases were more prevalent among women,
      except angina. Analysis by educational level showed that the diabetes prevalence
      rate was significantly larger among those with incomplete schooling. Although the
      six diseases presented different treatment coverage rates, for individuals with
      diagnosis of any one of the six diseases, the self-rated health was always worst,
      even after controlling for age and sex.

PMID- 16462997
TI  - Socio-demographic determinants of self-rated health in Brazil.
AB  - Self-rated health has been used extensively in epidemiologic studies, not only
      due to its importance per se but also due to the validity established by its
      association with clinical conditions and with greater risk of subsequent
      morbidity and mortality. In this study, the socio-demographic determinants of
      good self-rated health are analyzed using data from the World Health Survey,
      adapted and carried out in Brazil in 2003. Logistic regression models were used,
      with age and sex as covariables, and educational level, a household assets index,
      and work-related indicators as measures of socioeconomic status. Besides the
      effects of sex and age, with consistently worst health perception among females
      and among the eldest, the results showed pronounced socioeconomic inequalities.
      After adjusting for age, among females the factors that contributed most to
      deterioration of health perception were incomplete education and material
      hardship; among males, besides material hardship, work related indicators (manual
      work, unemployment, work retirement or incapable to work) were also important
      determining factors. Among individuals with long-term illness or disability, the
      socioeconomic gradient persisted, although of smaller magnitude.

PMID- 16462998
TI  - Perception of health state and the use of vignettes to calibrate for
      socioeconomic status: results of the World Health Survey in Brazil, 2003.
AB  - As part of the World Health Organization (WHO) project focused on assessing the
      performance of national health systems, the World Health Survey (WHS) was carried
      out in many member countries. In order to enable comparison of self-rated health
      between different cultures of the same country or between different nations, the
      WHS questionnaire included vignettes of sample cases, that is, hypothetical
      stories that describe the health problems of third parties. The objective of the
      present study is to evaluate the possibility of using vignette ratings to
      implement a socioeconomic calibration scale for self-rated health in Brazil.
      Using Brazilian WHS data, perceptions of state of health, measured through two
      different strategies (self-rating and vignette-rating), were compared. The
      effects of socioeconomic status (educational level and number of household
      assets) on health domain ratings were estimated via multiple regression models,
      controlled for age and sex. The effects of socioeconomic status were significant
      for the majority of health domains in the case of self-perception, but
      statistically null in the case of third party ratings. It is concluded that the
      WHO vignettes are not appropriate for calibrating self-rated health measures in
      Brazil.

PMID- 16462999
TI  - Healthy lifestyles and access to periodic health exams among Brazilian women.
AB  - Using data from the World Health Survey carried out in Brazil in 2003, this paper
      has the objective of describing the sociodemographic profile of Brazilian women
      (age 18-69 years of age) that have adequate health care, not only with respect to
      health service utilization but also to healthy lifestyles. Sociodemographic
      variables (age, marital status, race, education level, number of household
      assets, and occupation), health care variables (periodic gynecologic exam with
      Papanicolaou, mammography among women aged 40-69 years, body mass index, smoking,
      alcohol, physical activity, dental care, private health insurance), and self
      rated health were analyzed by municipality size strata. Logistic regression
      models were used to identify the characteristics of women that have adequate
      health care. Coverage of periodic gynecologic exam with Papanicolaou was 65.0%
      and mammography coverage was 47.0%. Less than 20.0% of Brazilian women have
      adequate care, and the most associated factors were: being younger than 40 years
      old, having higher educational level, having private health insurance and being
      married. The results indicate the need to develop health promotion policies
      focused on modifying the risk habits and risk practices to health, and to
      stimulate preventive periodic health exams.

PMID- 16463000
TI  - Sampling design for the World Health Survey in Brazil.
AB  - This paper describes the sample design used in the Brazilian application of the
      World Health Survey. The sample was selected in three stages. First, the census
      tracts were allocated in six strata defined by their urban/rural situation and
      population groups of the municipalities (counties). The tracts were selected
      using probabilities proportional to the respective number of households. In the
      second stage, households were selected with equiprobability using an inverse
      sample design to ensure 20 households interviewed per tract. In the last stage,
      one adult (18 years or older) per household was selected with equiprobability to
      answer the majority of the questionnaire. Sample weights were based on the
      inverse of the inclusion probabilities in the sample. To reduce bias in regional
      estimates, a household weighting calibration procedure was used to reduce sample
      bias in relation to income, sex, and age group.

PMID- 16463001
TI  - Utilization of medicines by the Brazilian population, 2003.
AB  - The aim of the present study was to characterize the utilization of medicines by
      the Brazilian population, using data from the Brazilian World Health Survey.
      Medicines were grouped according to the active pharmaceutical ingredient based on
      an adaptation of the World Health Organization standard list of essential
      medicines. The analysis included the characteristics of individuals who keep
      medicines at home and who had used them within the reference period (within two
      weeks prior to the interview), according to presence of medical prescription.
      Nearly half of the participants (49.0%) reported use of medicines during the
      reference period. Older and wealthier individuals and those with chronic diseases
      or disabilities and with poor self-rated health keep and use medicines more
      frequently. For 25.0% of the individuals that had used medicines during the
      reference period, none of the drugs had been prescribed by a health professional.
      Among the individuals who had medicines prescribed in the last appointment, 13.0%
      were unable to obtain the prescribed medication (of these, 55.0% could not afford
      it). The most widely utilized group was that of the analgesics (22.0%), and only
      51.0% of the individuals using this type of medicine had received a medical
      prescription for it.

PMID- 16463002
TI  - Health care users' satisfaction in Brazil, 2003.
AB  - Evaluation of users' satisfaction with the health system brings back longstanding
      questions concerning the quality of services provided to the Brazilian
      population. The current study analyzes satisfaction with outpatient and inpatient
      care based on the results of the World Health Survey, conducted in Brazil in
      2003. To explain satisfaction with various aspects of care through a small number
      of factors, the factor analysis technique was used, through principal components
      analysis (PCA). Multiple regression models identified associations between
      satisfaction scores and different sociodemographic variables. For outpatient
      care, waiting time showed the lowest degree of satisfaction, and in the case of
      hospitalization, freedom to choose the physician was the worst evaluated aspect.
      Three components were extracted from the PCA, related respectively to
      satisfaction with health professionals, health services, and health problem
      solution. Multiple regression analysis showed that having experienced some type
      of discrimination (on the basis of gender, age, poverty, social class, skin
      color, or type of disease) and being an exclusive user of the public National
      Health System involved a lower degree of users' satisfaction.

PMID- 16463003
TI  - Coverage of the Brazilian population 18 years and older by private health plans:
      an analysis of data from the World Health Survey.
AB  - This study analyzes data from the World Health Survey (WHS) conducted in 2003,
      with a sample of 5,000 individuals 18 years and older. Some 24.0% of the
      interviewees had private health insurance, and the main variables associated with
      private coverage were number of household assets, age, level of education, formal
      employment, living in municipalities with more than 50,000 inhabitants, and good
      self-rated health. The socioeconomic profiles of needs for and use of health
      services in the population covered by private health plans are different,
      confirming the findings of other studies reporting that this population segment
      as a whole presents better health conditions and greater use of services as
      compared to the population without private coverage, even after adjusting for
      socio-demographic variables and self-rated health. The WHS data also suggest that
      individuals with private health plans do not always use their insurance to pay
      for services, except in the case of mammograms.

PMID- 16463004
TI  - A rapid and reliable detection system for the analysis of PMP22 gene dosage by
      MP/DHPLC assay.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with
      liability to pressure palsies (HNPP) are caused by a 1.5-Mb duplication and a
      deletion at chromosome 17p11.2-12 encompassing the peripheral myelin protein 22
      gene (PMP22), respectively. We developed a rapid and reliable detection system
      for duplications/deletions of the PMP22 gene based on measurement of gene copy
      number. The method involves amplification of a test locus with unknown copy
      number and a reference locus of known copy number by multiplex PCR (MP), followed
      by denaturing high-performance liquid chromatography (DHPLC) or capillary
      electrophoresis detection to identify single copy changes. Thirty-two patients
      with CMT1A, 17 patients with HNPP, and 61 unaffected individuals were analyzed.
      Using the same competitive MP protocol, the measured PMP22 gene dosage revealed
      concordant results between DHPLC and capillary electrophoresis analysis. The
      results of the MP/DHPLC or the MP/capillary electrophoresis assay were all
      confirmed by PCR-restriction fragment length polymorphism analysis. We concluded
      that the MP/DHPLC assay is an efficient, accurate, and reliable technique for
      gene dosage determination of the PMP22 gene for CMT1A duplication and HNPP
      deletion. This technique further extends the application of DHPLC as an
      alternative method for the measurement of gene amplifications and heterozygous
      deletions in different genetic diseases.

PMID- 16463005
TI  - Mutational screening of the RB1 gene in Italian patients with retinoblastoma
      reveals 11 novel mutations.
AB  - Retinoblastoma (RB, OMIM#180200) is the most common intraocular tumour in infancy
      and early childhood. Constituent mutations in the RB1 gene predispose individuals
      to RB development. We performed a mutational screening of the RB1 gene in Italian
      patients affected by RB referred to the Medical Genetics of the University of
      Siena. In 35 unrelated patients, we identified germline RB1 mutations in 6 out of
      9 familial cases (66%) and in 7 out of 26 with no family history of RB (27%).
      Using the single-strand conformational polymorphism (SSCP) technique, 11 novel
      mutations were detected, including 3 nonsense, 5 frameshift and 4 splice-site
      mutations. Only two of these mutations (1 splice site and 1 missense) were
      previously reported. The mutation spectrum reflects the published literature,
      encompassing predominately nonsense or frameshift and splicing mutations. RB1
      germline mutation was detected in 37% of our cases. Gross rearrangements outside
      the investigated region, altered DNA methylation, or mutations in non-coding
      regions, may be the cause of disease in the remainder of the patients. Some
      cases, e.g. a case of incomplete penetrance, or variable expressivity ranging
      from retinoma to multiple tumours, are discussed in detail. In addition, a case
      of pre-conception genetic counselling resolved by rescue of banked cordonal blood
      of the affected deceased child is described.

PMID- 16463006
TI  - Behavioral interventions for HIV-positive and HCV-positive drug users.
AB  - The nature, context and frequency of use of various licit and illicit non
      injection drugs associated with an elevated risk of HIV infection. Beyond HIV, a
      high proportion of HIV-infected IDUs are co-infected with HCV (hepatitis C
      virus). In this review, we provide a brief review of the epidemiology of these
      problems, discuss behavioral interventions that can reduce ongoing high risk
      behaviors among HIV-seropositive IDUs and MSM-DUs, and review the literature
      which has evaluated their effectiveness. The majority of these interventions have
      focused on HIV-seronegative heterosexuals and therefore need to be considered in
      this larger context; however, where possible we discuss the potential impact of
      these interventions among HIV-seropositive persons. In addition, we briefly
      discuss interventions which have the potential to simultaneously reduce ongoing
      transmission of both HIV and HCV. Finally, given the dearth of information on the
      effectiveness of behavioral interventions in reducing the burden of the HIV and
      HCV epidemics among persons already infected with either or both viruses, we
      describe some newer, promising interventions and offer suggestions for future
      studies.

PMID- 16463007
TI  - Positive effect of alendronate on bone mineral density and markers of bone
      turnover in patients with rheumatoid arthritis on chronic treatment with low-dose
      prednisone: a randomized, double-blind, placebo-controlled trial.
AB  - INTRODUCTION: Alendronate has been described to have a bone-sparing effect in
      patients treated with moderate and high dosages of prednisone for heterogeneous
      diseases, however no data are available on groups of patients with the same
      underlying diseases who receive chronic low-dose prednisone treatment. The
      objective of the investigation reported here was, therefore, to study the effect
      of alendronate on bone mineral density (BMD) of the lumbar spine and hips in
      patients with rheumatoid arthritis (RA) who are on chronic low-dose prednisone
      treatment. METHODS: A total of 163 patients with RA, according to the ACR
      criteria, were enrolled in a double-blind, placebo-controlled trial. The patients
      were treated with low-dose prednisone (<or=10 mg/day) for at least 3 months. The
      patients were randomized to receive daily doses of alendronate or placebo: men
      and premenopausal women received 5 mg alendronate (or placebo) daily;
      postmenopausal women received 10 mg alendronate (or placebo) daily. All patients
      received daily calcium (500 mg, or 1000 mg, depending on baseline dietary calcium
      intake) and vitamin D3 (400 IU) supplementation. BMD of the lumbar spine (L1-L4)
      and the (total) hip was measured at baseline and after 6 and 12 months. The
      primary endpoint was change in BMD of the lumbar spine after 12 months (ITT). At
      baseline and after 3 and 12 months, serum bone-specific alkaline phosphatase
      (BAP) and urinary excretion of N-telopeptide (NTX) were measured. Radiographs of
      the thoracic and lumbar spine were made at baseline and after 12 months and
      subsequently scored for vertebral deformities. RESULTS: The groups were
      comparable at baseline in age, gender, daily dosage of prednisone, BMD at the
      spine and the hip and markers of bone turnover, while the number of patients with
      prevalent vertebral deformities was slightly higher in the alendronate-treated
      patients (54% versus 39%, not significant). After 12 months, BMD at the lumbar
      spine had increased by 3.7% in the alendronate-treated patients and decreased by 
      1.0% in the placebo-treated patients (p<0.0001); at the hip, the changes were
      +1.0% and -0.1%, respectively (not significant). After 3 months, serum BAP had
      decreased by 16.9% in the alendronate group versus 3.3% in the placebo group
      (p=0.0005), while urinary NTX had decreased by 46.4% in the alendronate group
      versus 12.1% in the placebo group (p<0.0001). After 12 months, no statistically
      significant difference was found between the groups with respect to number of
      patients with incident vertebral or non-vertebral fractures. Adverse effects were
      relatively common in these patients with severe RA: adverse effects were observed
      in 68% of the alendronate-treated patients and in 73% of the placebo patients
      (not significant), while serious adverse events were observed in 13% and 17%,
      respectively (not significant). CONCLUSION: We observed a favourable effect of
      alendronate on the BMD of the lumbar spine and on the markers of bone turnover in
      patients with RA treated with low-dose prednisone. These data support the
      conclusion that the prescribing of alendronate is not only beneficial in patients
      treated with high-dose prednisone but also in RA patients chronically treated
      with low-dose prednisone.

PMID- 16463008
TI  - Depth profiling of compression-induced disorders and polymorphic transition on
      tablet surfaces with grazing incidence X-ray diffraction.
AB  - PURPOSE: The importance of induced crystal disorders like crystallite size,
      crystal defects, and amorphicity with respect to the dissolution rate of the drug
      has been discussed in many cases. Thus, the characterization of these properties
      is of great importance in the pharmaceutical formulation development, although
      the exact correlation between disorders and dissolution rate is still unclear.
      The aim of this study was to analyze pharmaceutical tablets with grazing
      incidence X-ray diffraction, which enables the depth profiling of the
      crystallographic properties of the tablets. To study and clarify the potential of
      grazing incidence diffraction in the analysis of pharmaceutical materials, the
      effect of the compaction process on the surface of tablets was examined. METHODS:
      Carbamazepine, tolbutamide, and chlorpropamide tablets, compacted using different
      compression pressures, were studied using grazing incidence angle X-ray
      diffraction. The effects of compression on the crystallographic properties were
      investigated as a function of the distance from the tablet surface. RESULTS: The
      surfaces of the tolbutamide and chlorpropamide tablets were disordered due to the
      compression. The manifestation of the disorder was deduced to be due to
      amorphicity, small crystallite size, and amount of crystal defects. The changes
      were mainly on the surface and diminished strongly as a function of the distance
      from the surface of the tablet. Moreover, the changes were dependent on the
      compression pressure used. The changes on the surface of the carbamazepine
      tablets were also due to the compression but these changes were not clearly
      dependent on the depth nor the compression pressure. The partial phase transition
      took place in the chlorpropamide tablets due to the compression. The magnitude of
      the transition was not highest on the surface because amorphization and
      texturization also took place on the tablet surface during the compression.
      CONCLUSIONS: The present study proved that grazing incidence X-ray diffraction is
      a potential novel research tool to reveal crystallographic transformations taking
      place on the surfaces of the tablets induced, for example, by compression
      pressure.

PMID- 16463009
TI  - Hydrophilic absorbable copolyester exhibiting zero-order drug release.
AB  - PURPOSE: A novel absorbable hydrophilic copolyester developed in our laboratory,
      amorphous 40/60 poly(ethylene diglycolate-co-glycolide), exhibits outstanding
      physical properties. Films made from this material appear fully transparent,
      colorless, soft and slightly elastic, but relatively strong and durable materials
      so that they can be potentially used as stand-alone devices in various in-vivo
      medical applications. In this study, in-vitro drug release characteristics of
      this copolyester were examined. METHODS: High Performance Liquid Chromatography
      was used to generate release profiles on selected non-steroidal anti-inflammatory
      agents, NSAIDs. In addition, dielectric relaxation spectroscopy, as well as mid-
      and near infrared spectroscopy, were used to study specific polymer chain
      interactions in water and buffer solution as a function of aging time at 37
      degrees C. RESULTS: This copolyester, compression molded into a film, exhibited
      nearly constant in-vitro release of various hydrophilic and hydrophobic drugs.
      The release profile showed minimal or, in most cases, no burst effect. The effect
      was observed with the three NSAIDs that were tested as model compounds; however,
      this system may prove generally useful for other drug entities. In-vitro
      hydrolysis conducted at 37 degrees C on this hydrophilic copolyester revealed an
      unusually long induction period (no hydrolysis for up to 6 days), followed by the
      relatively rapid hydrolysis. Data from dipole relaxation spectroscopy indicated
      that the water molecules do not structurally associate with the polymer chains in
      phosphate buffer during initial hydrolysis period. CONCLUSIONS: The results
      suggest unique dynamics of water diffusion through the polymer matrix that may
      play a critical role in achieving controlled release properties. Furthermore, we
      suspect that the molecular interactions associated with this new synthetic
      absorbable material may find a critical utility in important medical
      applications.

PMID- 16463011
TI  - The ability of YSR scales to predict DSM/DISC-C psychiatric disorders among
      incarcerated male adolescents.
AB  - OBJECTIVE: To investigate whether the empirical or DSM-oriented scales of the
      Youth Self-Report (YSR) can be used to screen for DSM psychiatric disorders among
      incarcerated boys. DSM-oriented scales have recently been developed by Achenbach
      to enhance comparability of YSR results with DSM diagnostic categories. METHOD: A
      representative sample (N = 196) of incarcerated boys aged 12-18 was assessed with
      the child version of the Diagnostic Interview Schedule for Children (DISC-C) to
      diagnose DSM psychiatric disorders, and with the Youth Self-Report (YSR).
      RESULTS: Only 22% had YSR total problem scores in the clinical range, whereas 90
      % met criteria of at least one DSM/DISC-C psychiatric disorder. Weak associations
      between both empirical and DSM-oriented YSR scale scores and DSM/DISC-C diagnoses
      were found. CONCLUSIONS: Neither the empirical nor the DSM-oriented YSR scales
      adequately screen for DSM/DISC-C psychiatric disorders among incarcerated boys.
      The use of the YSR and the DISC-C to assess DSM constructs results in, at least
      partially, different diagnostic information.

PMID- 16463010
TI  - Gene expression profiles in mouse lung tissue after administration of two
      cationic polymers used for nonviral gene delivery.
AB  - PURPOSE: This study compared gene expression profiles in mouse lungs after
      administration of the cationic polymers polyethyleneimine (PEI) or chitosan alone
      or formulated with a luciferase reporter plasmid (PEI-pLuc, chitosan-pLuc).
      METHODS: The polymers and formulations were administered intratracheally to
      Balb/c mice at doses judged to be nontoxic according to intracellular
      dehydrogenase activity and tissue morphology. RNA was isolated from the lungs 24
      or 72 h after administration, and a dedicated stress and toxicology cDNA array
      was used to monitor the in vivo response to the gene delivery system in the lung
      tissue. RESULTS: The gene expression profiles differed between the PEI and
      chitosan groups with regard to both the total number and the type of expressed
      genes. Chitosan-pLuc upregulated genes that protect the cell from oxidative
      stress and inflammation, such as heme oxygenase-1 and catalase, whereas PEI-pLuc
      upregulated genes involved in inflammatory processes, such as the cyclooxygenases
      1 and 2, indicating possible involvement in the development of adverse reactions.
      However, both polymers activated genes involved in reaction to stress, such as
      DNA damage repair. Furthermore, in the PEI group, chaperone genes and members of
      the p38 mitogen-activated protein kinase pathway were also upregulated,
      suggesting a possible explanation for the better performance of PEI in gene
      delivery systems. CONCLUSIONS: The results indicate that gene expression
      profiling is a useful and sensitive tool for the evaluation of tissue responses
      after administration of polymers or gene delivery systems. The results also
      suggest a possible explanation for the differences in gene delivery performance
      between the two polymers in gene delivery systems.

PMID- 16463012
TI  - Adolescent outcome of disruptive behaviour disorder in children who had been
      treated in in-patient and day-treatment settings.
AB  - Although several studies have been conducted on the longitudinal course of
      childhood disruptive behaviours in community samples and in general psychiatric
      samples, little is known about adolescent adjustment in psychiatrically treated
      disruptive behaviour disorder (DBD) children. We examined a sample of adolescents
      (n = 47) who had been treated as children in an in-patient and/or day-treatment
      setting because of their severely disruptive behaviour. At follow-up, we found
      that half of the adolescents had a DBD diagnosis, and on average higher numbers
      of participants ever used soft drugs, had ever been in court, were not attending
      school when this was mandatory, and were smoking on a daily basis, as compared to
      comparison groups. There was, however, a large variance among the adolescents of
      our sample. When outcome was defined in terms of DBD diagnosis, living status,
      delinquency, school attendance, and smoking behaviour, 38 % had a positive
      outcome and 34 % had a poor outcome. For clinical purposes, it is important to
      recognise that there are large individual differences in outcome.

PMID- 16463013
TI  - Gene expression analysis of human hepatocellular carcinoma by using full-length
      cDNA library.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Hepatitis B
      virus (HBV) or hepatitis C virus (HCV) infection has been shown to cause hepatic
      carcinogenesis. A total 58,251 of cDNA clones of full-length cDNA libraries of
      HBV and HCV-infected HCC and their surrounding non-tumor tissues, respectively,
      were sequenced and analyzed by blasting against GENEBANK maintained by NCBI.
      About 180 and 279 of genes were shown an obviously increased and decreased
      expression patterns between HCC tissue and its adjacent non-tumor tissue. The
      candidate genes consisted of the genes encoded liver specific metabolism enzymes,
      secretory functional proteins, proteases and their inhibitors, protein chaperon,
      cell cycle components, apoptosis-related proteins, transcriptional factors, and
      DNA binding proteins. Several genes were further investigated by using real-time
      PCR to confirm the gene expression levels in at least 24 pairs of HCC tissues and
      adjacent non-tumor tissues. The results showed that genes encoded reticulon 4,
      RGS-1, antiplasmin, and kallikrein B were down-regulated with the average of 2.8,
      8.5, 3.2, and 10.5-fold, respectively. Our results provide crucial candidate
      genes to develop clinical diagnosis and gene therapy of HCC.

PMID- 16463014
TI  - F-box proteins: the key to protein degradation.
AB  - The eukaryotic protein degradation pathway involves the ubiquitin (Ub)
      modification of substrates targeted for degradation by the 26S proteasome. The
      addition of Ub, a process called ubiquitination, is mediated by enzymes including
      the E3 Ub ligases which transfer the Ub to targeted substrates. A major type of
      E3 Ub ligases, the SCF (Skp-Cullin-F-box) complex, is composed of four major
      components: Skp1, Cul1/Cdc53, Roc1/Rbx1/Hrt1, and an F-box protein. The F-box
      component of the SCF machineries is responsible for recognizing different
      substrates for ubiquitination. Interaction with components of the SCF complex is
      mediated through the F-box motif of the F-box protein while it associates with
      phosphorylated substrates through its second protein-protein interaction motif
      such as Trp-Asp (WD) repeats or leucine-rich repeats (LRRs). By targeting diverse
      substrates, F-box proteins exert controls over stability of proteins and regulate
      the mechanisms for a wide-range of cellular processes. Here we discuss the
      importance of F-box proteins by providing a general overview and examples of how
      F-box proteins function in various cellular settings such as tissue development,
      cell proliferation, and cell death, in the modeling organism Drosophila.

PMID- 16463015
TI  - Pollutant effects on Pacific oyster, Crassostrea gigas (Thunberg), hemocytes:
      screening of 23 molecules using flow cytometry.
AB  - The shellfish industry is an important economic activity in France, occurring
      mostly in estuarine zones subject to pollution due to anthropogenic activities.
      The harmful effects of pollutants on species inhabiting these estuarine zones are
      not well known. Among marine species, bivalve mollusks--particularly Pacific
      oyster, Crassostrea gigas--may serve a model of interest. The species is
      sedentary and filter-feeding, which favors bioaccumulation of pollutants in their
      tissues. Oysters may be suitable for studies on disturbance by pollutants of
      physiological activities, among which defense mechanisms are poorly documented in
      bivalves. In this study, effects of pollutants on hemocyte functions were
      monitored in Pacific oyster, C. gigas. Hemocytes were exposed in vitro to
      selected pollutants. The strategy for investigating the effects of pollutants on
      hemocyte functions is based on several biomarkers, which is more relevant than
      that of published papers based on single-endpoint experiments. Pollutants
      belonging to the most important groups of xenobiotics (PAHs, PCBs, and
      pesticides) were selected and their effect on hemocyte activities was analyzed
      using flow cytometry. Twenty-three pollutants were tested and eight of them
      showed significant modulation of hemocyte activities. PAHs and PCB 77 induced a
      decrease of hemocyte activity after an incubation periods of 4 and 24 h at 200
      micro mol/L. Three pesticides (2,4D, paraoxon, and chlorothalonil) modulated
      hemocyte activities. A mixture of eight pesticides also decreased phagocytotic
      activity. This study is one of the first to investigate the effects of so many
      pollutants on hemocyte functions at the same time and therefore allows a real
      comparison of different pollutant effects.

PMID- 16463016
TI  - Validation of an in vitro screen for phospholipidosis using a high-content
      biology platform.
AB  - Several cationic amphiphilic drugs cause local or systemic phospholipidosis (PLD)
      after chronic exposure in preclinical species. PLD is characterized by the
      accumulation of drug, phospholipid, and concentric lamellar bodies in cellular
      lysosomes. We have developed a fluorescence-based in vitro screen that is
      predictive of PLD using the Cellomics ArrayScan high-content screening platform,
      which captures and analyzes images from 96-well cell culture microtiter plates
      using multichannel fluorescence microscopy. I-13.35 adherent mouse spleen
      macrophage cells were cultured with drug and a fluorescently tagged phospholipid,
      N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3
      phosphoethanolamine (NBD-PE). Drug concentrations were used in a range from 1 to
      100 micro mol/L. After 24 h incubations, the cells were fixed with formalin. NBD
      PE uptake was quantified in controls and treated cells. Nuclei were identified by
      Hoechst 33258 staining and dead cells were identified using ethidium homodimer-2
      incorporation. Thus, confounding accumulation of NBD-PE due to cytotoxicity that
      produces false-positive results at high concentrations was eliminated from
      quantitation by ethidium staining and employing cell gating (dead cell
      rejection). The assay was found to be both sensitive and selective in that 26 of
      28 positive, phospholipidogenic controls and 8 of 8 negative, non
      phospholipidogenic controls were correctly called.

PMID- 16463017
TI  - Why does ethanol induce cellular heat-shock response?
AB  - At the time of induction of the periplasmic protein alkaline phosphatase (AP) in
      Escherichia coli, the presence of ethanol (10% v/v) in the growth medium did not
      allow the induced AP to be translocated out to the periplasm. The nontransported
      AP was stored in the cytoplasm as the unfolded precursor form (AP with its amino
      terminal signal sequence), which had no enzymatic activity. The presence of 10%
      v/v ethanol in the growth medium also induced the heat-shock response in E. coli,
      which was evident from the enhanced syntheses of several heat-shock proteins
      (HSPs) over their cellular basal levels. These results, in conjunction with our
      earlier findings on the occurrence of heat-shock response in an AP-signal
      sequence mutant of E. coli due to the export deficiency of AP precursor, suggest
      that the membrane protein precursors, stored in the cytoplasm due to the ethanol
      mediated inhibition of translocation, behaved to the cells as abnormal proteins,
      which ultimately triggered the signal for the induction of heat-shock response in
      E. coli.

PMID- 16463018
TI  - Effects of hydrogen peroxide (H2O2) on alkaline phosphatase activity and matrix
      mineralization of odontoblast and osteoblast cell lines.
AB  - Hydrogen peroxide (H(2)O(2)), an oxidizing agent, has been widely used as a
      disinfectant. Recently, because of its reactive properties, H(2)O(2) has also
      been used as a tooth bleaching agent in dental care. This is a cause for concern
      because of adverse biological effects on the soft and hard tissues of the oral
      environment. To investigate the influence of H(2)O(2) on odontoblasts, the cells
      producing dentin in the pulp, we assessed cellular viability, generation of
      reactive oxygen species (ROS), alkaline phosphatase (ALP) activity, and nodule
      formation of an odontoblastic cell line (MDPC-23) after treatment with H(2)O(2),
      and compared those with the effects on preosteoblastic MC3T3-E1 cells. Cytotoxic
      effects of H(2)O(2) began to appear at 0.3 mmol/L in both MDPC-23 and MC3T3-E1
      cells. At that concentration, the accumulation of intracellular ROS was confirmed
      by a fluorescent probe, DCFH-DA. Although more ROS were detected in MDPC-23, the
      increasing pattern and rate are similar between the two cells. When the cells
      were treated with H(2)O(2) at concentrations below 0.3 mmol/L, MDPC-23 displayed
      a significant increase in ALP activity and mineralized bone matrix, while MC3T3
      E1 cells showed adverse effects of H(2)O(2). It is known that ROS are generally
      harmful by-products of aerobic life and represent the primary cause of aging and
      numerous diseases. These data, however, suggest that ROS can induce in vitro cell
      differentiation, and that they play a more complex role in cell physiology than
      simply causing oxidative damage.

PMID- 16463019
TI  - L-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits
      leukocyte death.
AB  - Methotrexate (MTX), a folic acid antagonist widely used for the treatment of a
      variety of tumors and inflammatory diseases, affects normal tissues that have a
      high rate of proliferation, including the hematopoietic cells of the bone marrow
      and the gastrointestinal mucosal cells. To elucidate the role of free radicals
      and leukocytes in MTX-induced oxidative organ damage and the putative protective
      effect of L-carnitine (L-Car), Wistar albino rats were administered a single dose
      of MTX (20 mg/kg) followed by either saline or L-Car (500 mg/kg) for 5 days.
      After decapitation of the rats, trunk blood was obtained, and the ileum, liver,
      and kidney were removed for histological examination and for the measurement of
      malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO)
      activity, and collagen content. Our results showed that MTX administration
      increased the MDA and MPO activities and collagen content and decreased GSH
      levels in all tissues, while these alterations were reversed in L-Car-treated
      group. The elevated serum TNF-alpha level observed following MTX treatment was
      depressed with L-Car. The oxidative burst of neutrophils stimulated by Annexin V
      was reduced in the saline-treated MTX group, while L-Car abolished this
      inhibition. Similarly, flow cytometric measurements revealed that leukocyte
      apoptosis was increased in MTX-treated animals, while L-Car reversed these
      effects. Severe degeneration of the intestinal mucosa, liver parenchyma, and
      glomerular and tubular epithelium observed in the saline-treated MTX group was
      improved by L-Car treatment. These results suggest that L-Car, possibly via its
      free radical scavenging and antioxidant properties, ameliorates MTX-induced
      oxidative organ injury and inhibits leukocyte apoptosis. Thus, supplementation
      with L-Carnitine as an adjuvant therapy may be promising in alleviating the
      systemic side-effects of chemotherapeutics.

PMID- 16463020
TI  - Structurally similar diazenes exhibit significantly different biological
      activity.
AB  - We have previously synthesized various diazenecarboxamides (subsequently referred
      to as diazenes) that were cytotoxic to several tumor cell lines. To increase
      their biological activity, the structure has been modified appropriately. In the
      present study we examined the effects of N(1)-phenyl-N(2)-(2
      pyridinylmethyl)diazenedicarboxamide (RL-337) obtained from the previously
      examined cytotoxic compound N(1)-phenyl-N(2)-(2-pyridinyl)diazenecarboxamide (JK
      279), and compared them with those of diazene JK-279. Using a modified
      colorimetric MTT assay, the cytotoxicity of RL-337 was determined on human
      cervical carcinoma HeLa cells, glioblastoma A1235 cells, and prostate
      adenocarcinoma PC-3 cells. The possible synergistic effect of diazene RL-337 with
      cisplatin, doxorubicin, and vincristine, and its influence on intracellular GSH
      content was examined on HeLa cells. Diazene RL-337 was cytotoxic against all
      three human tumor cell lines, being more cytotoxic to HeLa cells than diazene JK
      279. The higher efficacy of RL-337 than of JK-279 can be connected with higher
      basicity of the 2-picoline moiety present in the former diazene comparing with
      the pyridine fragment that is a part of the latter. The diazene RL-337 acted
      synergistically with cisplatin, doxorubicin, and vincristine (diazene JK-279
      exhibited synergistic effect only with cisplatin). Glutathione (determined by
      Tietze's method) was not a target molecule of diazene RL-337 (but was for JK-279,
      as shown earlier). After just 1 h treatment with diazene RL-337, the cells
      started to lose membrane integrity. There was no cleavage of caspase-3 in RL-337
      treated samples, and the majority of cells died 6 h after the treatment through
      necrosis (previously, apoptosis-like cell death was detected for diazene JK-279).
      Thus, although diazenes JK-279 and RL-337 are very similar in their structure,
      they exhibit widely different biological activity.

PMID- 16463021
TI  - Cysteine S-conjugate beta-lyases.
AB  - Cysteine S-conjugate beta-lyases are pyridoxal 5'-phosphate-containing enzymes
      that catalyze beta-elimination reactions with cysteine S-conjugates that possess
      an electron-withdrawing group attached at the sulfur. The end products of the
      beta-lyase reaction are pyruvate, ammonium and a sulfur-containing fragment. If
      the sulfur-containing fragment is reactive, the parent cysteine S-conjugate may
      be toxic, particularly to kidney mitochondria. Halogenated alkenes are examples
      of electrophiles that are bioactivated (toxified) by conversion to cysteine S
      conjugates. These conjugates are converted by cysteine S-conjugate beta-lyases to
      thioacylating fragments. Several cysteine S-conjugates found in allium foods
      (garlic and onion) are beta-lyase substrates. This finding may account in part
      for the chemopreventive activity of allium products. This review (1) identifies
      enzymes that catalyze cysteine S-conjugate beta-lyase reactions, (2) suggests
      that toxicant channeling may contribute to halogenated cysteine S-conjugate
      induced toxicity to mitochondria, and (3) proposes mechanisms that may contribute
      to the antiproliferative effects of sulfur-containing fragments eliminated from
      allium-derived cysteine S-conjugates.

PMID- 16463022
TI  - Genetic influence on human lifespan and longevity.
AB  - There is an intense search for longevity genes in both animal models and humans.
      Human family studies have indicated that a modest amount of the overall variation
      in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But
      it is not known if genetic factors become increasingly important for survival at
      the oldest ages. We study the genetic influence on human lifespan and how it
      varies with age using the almost extinct cohorts of Danish, Finnish and Swedish
      twins born between 1870 and 1910 comprising 20,502 individuals followed until
      2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and
      then turn to the relative recurrence risk of surviving to a given age. Mean
      lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)]
      years for every year his co-twin survives past age 60 years. This rate is
      significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ)
      males. Females and males have similar rates and these are negligible before age
      60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to
      old ages substantially and significantly increases the chance of reaching the
      same old age and this chance is higher for MZ than for DZ twins. The relative
      recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is
      significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for
      females and males are very similar, but with a shift of the female pattern with
      age that corresponds to the better female survival. Similar results arise when
      considering only those Nordic twins that survived past 75 years of age. The
      present large population based study shows genetic influence on human lifespan.
      While the estimated overall strength of genetic influence is compatible with
      previous studies, we find that genetic influences on lifespan are minimal prior
      to age 60 but increase thereafter. These findings provide a support for the
      search for genes affecting longevity in humans, especially at advanced ages.

PMID- 16463023
TI  - Identification of novel functional variants of the melanocortin 1 receptor gene
      originated from Asians.
AB  - Human melanocortin 1 receptor (MC1R) is a seven transmembrane G-coupled protein
      receptor that upregulates the cAMP pathway. Several functional variants of MC1R
      that show an impaired ability to activate the cAMP pathway are strongly
      associated with fair skin and red hair in Europeans and European descendants. The
      sequence variations of the MC1R gene were repeatedly investigated against
      worldwide populations; however, there was no evidence that functional variant of
      MC1R exists in non-European descendants. We report the presence of novel
      functional variants of MC1R with Asian origins. Three novel variants of MC1R,
      Phe147Delta, Thr157Ile, and Pro159Thr, were identified in our screening for the
      sequence variations of the MC1R gene against 995 individuals from 30 Asian and
      Oceanian populations; there was a single case for the Pro159Thr variant allele
      and two instances of Phe147Delta and Thr157Ile variant alleles. Our
      pharmacological assay revealed that Phe147Delta, Thr157Ile, and Pro159Thr variant
      showed similar or more dramatically impaired activities in comparison with
      Arg151Cys, which is a major functional variant of MC1R in Europeans. These
      functional variant alleles were geographically localized in relatively high
      latitudes, which suggest that the adaptation to ambient UV light intensity may
      play an important role in shaping the geographical distribution of MC1R alleles
      in Asia and Oceania.

PMID- 16463025
TI  - The discovery of the human chromosome number in Lund, 1955-1956.
AB  - The correct determination of the human diploid chromosome number as 46, by J-H
      Tjio and A Levan, at the University of Lund, Sweden, occurred 50 years ago, in
      December 1955; the finding was published in April 1956, ending a period of more
      than 30 years when the number had been thought to be 48. The background to the
      discovery and the surrounding factors are reassessed, as are the reasons why
      previous investigators persistently misidentified the precise number. The
      necessity for multiple technological advances, the power of previously accepted
      conclusions in influencing the interpretation of later results, and the
      importance of other work already undertaken in Lund, are all relevant factors for
      the occurrence of this discovery, the foundation for modern human cytogenetics,
      at this particular time and place.

PMID- 16463024
TI  - The TNFalpha receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium
      channel ENaC as modulators in cystic fibrosis.
AB  - The CFTR mutations in cystic fibrosis (CF) lead to ion transport anomalities
      which predispose to chronic infection and inflammation of CF airways as the major
      determinants for morbidity and mortality in CF. Discordant clinical phenotypes of
      siblings with identical CFTR mutations and the large variability of clinical
      manifestations of patients who are homozygous for the most common mutation
      F508del suggest that both environment and genes other than CFTR contribute
      substantially to CF disease. The prime candidates for genetic modifiers in CF are
      elements of host defence such as the TNFalpha receptor and of ion transport such
      as the amiloride-sensitive epithelial sodium channel ENaC, both of which are
      encoded side by side on 12p13 (TNFRSF1A, SCNN1A) and 16p12 (SCNN1B, SCNN1G).
      Thirty-seven families with F508del-CFTR homozygous siblings exhibiting extreme
      clinical phenotypes that had been selected from the 467 pairs of the European CF
      Twin and Sibling Study were genotyped at 12p13 and 16p12 markers. The ENaC was
      identified as a modulator of CF by transmission disequilibrium at SCNN1G and
      association with CF phenotype intrapair discordance at SCNN1B. Family-based and
      case-control analyses and sequencing of SCNN1A and TNFRSF1A uncovered an
      association of the TNFRSF1A intron 1 haplotype with disease severity. Carriers of
      risk haplotypes were underrepresented suggesting a strong impact of both loci on
      survival. The finding that TNFRSF1A, SCNN1B and SCNN1G are clinically relevant
      modulators of CF disease supports current concepts that the depletion of airway
      surface liquid and inadequate host inflammatory responses trigger pulmonary
      disease in CF.

PMID- 16463027
TI  - Perinatal assessment of hereditary cystic renal diseases: the contribution of
      sonography.
AB  - The aims of this review article were to clarify the steps that may lead to a
      proper diagnosis of fetal and neonatal renal cystic diseases. All the hereditary
      cystic diseases are reviewed and a classification is proposed. The various
      sonographic patterns that can be used to ascertain the diagnosis are also
      reviewed. Finally, tables with differential diagnoses are presented to help the
      reader in the work-up of such pathologies.

PMID- 16463028
TI  - Enhanced CT perfusion cut-off sign in midgut volvulus.
AB  - We present a case of malrotation with midgut volvulus in an infant in which we
      discovered a unique CT sign called the perfusion cut-off sign. We hope this case
      will help establish this crucial diagnosis in other cases.

PMID- 16463029
TI  - Basal ganglia germinoma in children with associated ipsilateral cerebral and
      brain stem hemiatrophy.
AB  - BACKGROUND: Germinoma is the most common and least-malignant intracranial germ
      cell tumor, usually found in the midline. Germinoma that arises in the basal
      ganglia, called ectopic germinoma, is a rare and well-documented entity
      representing 5% to 10% of all intracranial germinomas. The association of
      cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is
      found in 33% of the cases. OBJECTIVE: To review the literature and describe the
      CT and MRI findings of basal ganglia germinoma in children, known as ectopic
      germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy.
      MATERIALS AND METHODS: Three brain CT and six brain MRI studies performed in four
      children at two institutions were retrospectively reviewed. All patients were
      male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years),
      with pathologically proved germinoma arising in the basal ganglia, and associated
      ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It
      is important to note that three of these children presented with cognitive
      decline, psychosis and slowly progressive hemiparesis as their indication for
      imaging. RESULTS: Imaging results on initial scans were varied. In all patients,
      the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy,
      representing Wallerian degeneration. All patients who underwent CT imaging
      presented with a hyperdense or calcified lesion in the basal ganglia on
      unenhanced scans. Only one of these lesions had a mass effect on the surrounding
      structures. In one of these patients a large, complex, heterogeneous mass
      appeared 15 months later. Initial MR showed focal or diffusely increased T2
      signal in two cases and heterogeneous signal in the other two. CONCLUSION: The
      association of a focal lesion in the basal ganglia of children with progressive
      hemiparesis, neuropsychiatric symptoms and ipsilateral cerebral and/or brain stem
      hemiatrophy should prompt the diagnosis of ectopic germinoma, avoiding delay in
      the diagnosis and further irreversible clinical deterioration, in a malignancy
      with an otherwise favorable prognosis. In these patients, hemiatrophy preceding
      or accompanying the imaging depiction of a basal ganglia mass lesion is thought
      to be caused by a paraneoplastic process.

PMID- 16463030
TI  - Whole-body MRI in the detection of bone marrow infiltration in patients with
      plasma cell neoplasms in comparison to the radiological skeletal survey.
AB  - To compare the diagnostic value of whole-body MRI versus radiological skeletal
      survey (RSS) in staging patients with plasma cell neoplasms (PCN) and to evaluate
      the possible therapeutic impact of the replacement of RSS by whole-body MRI.
      Fifty-four patients with PCN [multiple myeloma (MM), n=47; monoclonal gammopathy
      of unknown significance (MGUS), n=7] were studied by whole-body MRI and RSS in a
      monocenter prospective analysis from August 2002 to May 2004. The MRIs were
      performed using a rolling table platform "AngioSURF" for unlimited field of view
      with a 1.5-T system (Magnetom Sonata/Maestro Class, Siemens Medical Solutions,
      Erlangen, Germany). A coronal STIR sequence (TR5500-4230/TE102-94/TI160) was used
      for imaging of the different body regions, including the head, neck, thorax,
      abdomen, pelvis and upper and lower extremities. The RSS consisted of eight
      different projections of the axial and appendicular skeleton. In 41/54 (74%)
      patients, the results of the whole-body MRI and RSS were concordant. In 11/54
      (20%) patients, both imaging techniques were negative. Bone involvement was
      observed in 30/54 (55%) patients; however, whole-body MRI revealed this more
      extensively than the RSS in 27/30 (90%) patients with concordant positive imaging
      findings. In 3/30 (10%) patients, both imaging techniques demonstrated a similar
      extent of bone marrow infiltration. In 10/54 (19%) patients, the whole-body MRI
      was superior to RSS in detecting bone marrow infiltration, whereas the RSS was
      negative. In 3/54 (6%) patients, the RSS was proven to be false positive by the
      clinical course, whereas the whole-body MRI was truly negative. Whole-body MRI is
      a fast and highly effective method for staging PCN patients by the use of a
      rolling table platform. Moreover, it is more sensitive and specific than RSS and
      reveals bone marrow infiltration and extensive disease more reliably. Therefore,
      whole-body MRI should be performed as an additional method of exactly staging PCN
      patients and - with more data in the field - may even prove to be an alternate
      and more sensitive staging procedure than RSS in PCN patients.

PMID- 16463031
TI  - Signal intensity of the normal pontine tegmentum on T2-weighted MR imaging.
AB  - On T2-weighted MR images, the pontine tegmentum frequently shows a signal of high
      intensity in neurologically healthy individuals. We examined whether the signal
      intensity of the pontine tegmentum normally differs from that of the pontine
      base. We evaluated the signal intensity of the pontine tegmentum and pontine base
      on T2-weighted images from 38 neurologically healthy subjects. The subjects
      included 29 adults (16 males and 13 females, age range 23-48 years, mean age 39.5
      years) and 9 children (4 boys and 5 girls (age range 4-9 years mean age 6.5
      years). We compared the contrast-to-noise ratio (CNR) between the tegmentum and
      the base in the upper pons, midpons and lower pons, and evaluated the signal
      intensity ratio of the tegmentum to the base. The CNR was significantly higher
      for the tegmentum than the base at each level of the pons (P<0.0001), and the
      signal intensity ratio of the tegmentum to the base in the upper pons was
      significantly higher in children than in adults (P<0.005). On T2-weighted images,
      a high signal intensity of the pontine tegmentum is frequently seen in
      neurologically healthy subjects. This finding should not be considered abnormal,
      particularly in children.

PMID- 16463032
TI  - FISH investigation of 22q11.2 deletion in patients with immunodeficiency and/or
      cardiac abnormalities.
AB  - DiGeorge anomaly/velocardiofacial syndrome (DG/VCFS), called 22q11.2 deletion
      syndrome in general, is the most common chromosomal deletion syndrome found in
      humans. Typical facial features, palatal defects, conotruncal abnormalities of
      the heart, aplasia/hypoplasia of the parathyroid glands and of thymus are
      characteristics of this syndrome. Deletions of chromosome 22q11.2 (del22q11.2)
      are the leading causes of DG7VCFS. We report on a systematic search by
      fluorescence in situ hybridization (FISH) for deletions of chromosomes 22q11.2 in
      patients with a clinical suspicion or diagnosis of DG/VCFS. Using FISH we studied
      a series of 43 patients with suspected DG/VCFS. In this study, a total of 43
      patients were investigated for the presence of a 22q11.2 deletion over a two-year
      period. Del22q11.2 was detected in 5 of the 43 patients tested. All patients with
      deletion had hypocalcemia, 80% had cardiac defects, 40% had facial dysmorphism,
      40% had immunodeficiency , and 20% had otolaryngeal abnormalities. Chromosome
      22q11.2 deletion is a relatively common condition and is readily diagnosed by
      FISH. We suggest that FISH analysis of 22q11.2 deletion should be performed in
      the presence of combined of hypocalcemia and congenital cardiac malformations,
      with or without any characteristics of the disease. This may facilitate an early
      diagnosis in such patients.

PMID- 16463033
TI  - Long-term outcome of patients with enterocolitis complicating Hirschsprung's
      disease.
AB  - Enterocolitis remains the most serious complication of Hirschsprung's disease
      (HD). The purpose of this study was to evaluate the risk factors in the
      development of enterocolitis and the long-term outcome in these patients. The
      hospital records of 259 consecutive patients with HD during 1975-2003 were
      examined. The data was analysed for age at presentation, associated anomalies,
      level of aganglionosis, clinical features, number of episodes of enterocolitis,
      type of pullthrough, necessity for post-pullthrough sphincterectomy. Follow up
      was carried out by personal interviews and interviews over the telephone with
      patients/parents. Enterocolitis was diagnosed on the basis of clinical features
      of diarrhoea, pyrexia, abdominal distention and vomiting. Of the 259 patients
      with HD, 74 patients (28.5%) were found to have enterocolitis. Out of 39 patients
      with Down's syndrome and HD, 19 (48%) had enterocolitis. Fifteen (20%) patients
      had other associated anomalies. Fifty-six patients (75.6%) were male and 18
      (24.3%) were female. In 30 patients enterocolitis was the presenting feature in
      the neonatal period, 22 of which presented in the first 2 weeks of life. Fifty
      six patients (75.6%) had rectosigmoid disease and 18 (24.3%) had long segment
      disease or total colonic aganglionosis. Eighteen (24.3%) had only preoperative
      enterocolitis and 31(41.8%) had only postoperative enterocolitis. Twenty-five
      (33.7%) had both pre- and post-operative enterocolitis. Twenty (27%) patients had
      more than 2 episodes of enterocolitis. Various pullthrough procedures were
      performed. Twenty-six patients (35.1%) required internal sphinctermyectomy to
      treat the enterocolitis. At the time of follow-up, 16 patients were lost to
      follow-up. Of the remaining 58 patients, 3 patients died, 2 due to enterocolitis
      and 1 due to sepsis. Six patients remained with a stoma. Twenty-two patients were
      continent and were stooling normally, but 14 of these were on laxatives for
      several years after pullthrough procedure. The mean age at achieving full
      continence was 4.95 years in the 22 patients with normal bowel function. Nineteen
      patients are still on laxatives and 8 patients are soiling. Eight patients
      continue to have multiple recurrent episodes of enterocolitis at follow-up.
      Down's syndrome is an important risk factor in the development of enterocolitis.
      The majority of patients with enterocolitis complicating HD continue to have
      disturbances of bowel function many years after surgery for HD.

PMID- 16463034
TI  - Gastrointestinal stromal tumour presenting with severe bleeding: a review of the
      molecular biology.
AB  - Gastrointestinal stromal tumours (GIST) are rare in children. A 7-year-old boy
      presented acutely with a severe upper gastrointestinal bleed and was found
      following angiography to have such a tumour in the duodenum, which was resected
      at laparotomy. The presence of CD 117 positive immunostaining was a confirmatory
      diagnostic marker. The prognosis and underlying molecular biology of the tumour
      is discussed. Understanding of the molecular pathogenesis has given rise to
      promising new therapies.

PMID- 16463035
TI  - Bone mineral density in Iranian patients with inflammatory bowel disease.
AB  - Patients with inflammatory bowel disease (IBD) are at increased risk of
      developing osteopenia and osteoporosis. The aim of the study was to investigate
      the prevalence of decreased bone density and related risk factors in Iranian IBD
      patients. A total of 126 ulcerative colitis (UC) and 39 Crohn's disease (CD)
      patients were enrolled. Dual-energy x-ray absorptiometry technique was used to
      measure bone density, and blood samples were obtained to measure biochemical
      markers. To find predictive variables for bone mineral density (BMD), stepwise
      regression analysis was carried out. A total of 53 IBD patients (32.1%) had
      diminished bone mineral density at either lumbar spine (L1-L4) or femoral neck.
      Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral
      neck bone density was significantly decreased among CD patients (p<0.04). There
      was no significant difference in BMD between men and women. We have found
      significant differences in BMD T scores at lumbar L1-L4, L2-L4, and femoral neck
      in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was
      no significant difference in biochemical markers between UC and CD patients,
      except that more CD patients were hypocalcemic (p<0.001). Stepwise regression
      analysis has revealed lumbar spine T score was predicted by age (p<0.0001),
      corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however,
      femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009),
      and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients
      is in accordance with Western societies. Treatment with corticosteroid has
      increased this possibility in both groups. Corticosteroid use, age, smoking, and
      BMI are predictive factors for low bone density.

PMID- 16463036
TI  - Issues and concerns of young Australian women with breast cancer.
AB  - GOALS OF WORK: Young women tend to experience many similar issues to that of
      their older counterparts, although more negatively and intensively. However, they
      also have specific concerns, which are not so apparent in studies that include a
      wide age range of participants. The aim of this study was to identify and explore
      the issues and concerns of Australian women diagnosed with breast cancer before
      age 41 years. PARTICIPANTS AND METHODS: We conducted in-depth, semi-structured
      interviews with a self-selected, convenience sample of 35 Australian women with
      breast cancer, diagnosed at 40 years of age or younger and no more than 4 years
      previously. Themes found within the literature about 'younger' women up to 50
      years of age provided guidance to the interviews. The audiotaped interviews were
      transcribed verbatim. The data were analysed using the basic analytical
      principles of data reduction, data display and drawing conclusions. The data were
      initially subdivided according to the literature-derived themes. Content analysis
      was performed on the categories developed, revealing the most pressing concerns
      of participants. MAIN RESULTS: Second to fear of recurrence and future
      uncertainty, children and family were the most commonly reported major personal
      concern. Consumer-related issues and concerns for children and family were
      equally reported as the greatest general concern of young women with breast
      cancer. The greatest unmet need of participants was support. CONCLUSIONS: Age
      appropriate information and support for this group of young women with breast
      cancer remains a challenge. This paper suggests ways young Australian women with
      breast cancer can access additional support with the use of technology.

PMID- 16463037
TI  - [Systemic photoprotection through carotenoids].
AB  - Nutritional supplements are increasingly used to protect human skin against
      environmentally-induced damage, most importantly as a consequence of ultraviolet
      radiation exposure. beta-carotene is a major constituent of comercially available
      products administered for systemic photoprotection. Studies on the systemic use
      of beta-carotene provide evidence that 15-30 mg/d over a period of about 10-12 wk
      produces a protective effect against UV-induced erythema. Similar effects have
      been attributed to mixtures of carotenoids or after long-term intake of dietary
      products rich in carotenoids. Supplementation with carotenoids contributes to
      basal protection of the skin but is not sufficent to obtain complete protection
      against severe UV irradiation.

PMID- 16463038
TI  - Enhancement of anti-tumor immunity specific to murine glioma by vaccination with
      tumor cell lysate-pulsed dendritic cells engineered to produce interleukin-12.
AB  - AIM: The aim of this study was to develop an immunotherapy specific to a
      malignant glioma by examining the efficacy of glioma tumor-specific cytotoxic T
      lymphocytes (CTL) as well as the anti-tumor immunity by vaccination with
      dendritic cells (DC) engineered to express murine IL-12 using adenovirus-mediated
      gene transfer and pulsed with a GL26 glioma cell lysate (AdVIL-12/DC+GL26) was
      investigated. EXPERIMENT1: For measuring CTL activity, splenocytes were harvested
      from the mice immunized with AdVIL-12/DC+GL26 and restimulated with syngeneic
      GL26 for 7 days. The frequencies of antigen-specific cytokine-secreting T cell
      were determined with mIFN-gamma ELISPOT. The cytotoxicity of CTL was assessed in
      a standard 51Cr-release assay. For the protective study in the subcutaneous tumor
      model, the mice were vaccinated subcutaneously (s.c) with 1x10(6) AdVIL
      12/DC+GL26 in the right flanks on day -21, -14 and -7. On day 7, the mice were
      challenged with 1x10(6) GL26 tumor cells in the shaved left flank. For a
      protective study in the intracranial tumor model, the mice were vaccinated with
      1x10(6) AdVIL-12/DC+GL26 s.c in the right flanks on days -21, -14 and -7. Fresh
      1x10(4) GL26 cells were inoculated into the brain on day 0. To prove a
      therapeutic benefit in established tumors, subcutaneous or intracranial GL26
      tumor-bearing mice were vaccinated s.c with 1x10(6) AdVIL-12/DC+GL26 on day 5, 12
      and 19 after tumor cell inoculation. RESULTS: Splenocytes from the mice
      vaccinated with the AdVIL-12/DC+GL26 showed enhanced induction of tumor-specific
      CTL and increased numbers of IFN-gamma: secreting T cells by ELISPOT. Moreover,
      vaccination of AdVIL-12/DC+GL26 enhanced the induction of anti-tumor immunity in
      both the subcutaneous and intracranial tumor models. CONCLUSIONS: These
      preclinical model results suggest that DC engineered to express IL-12 and pulsed
      with a tumor lysate could be used in a possible immunotherapeutic strategy for
      malignant glioma.

PMID- 16463039
TI  - Hypochlorous acid enhances immunogenicity and uptake of allogeneic ovarian tumor
      cells by dendritic cells to cross-prime tumor-specific T cells.
AB  - BACKGROUND: Ovarian cancer commonly relapses after remission and new strategies
      to target microscopic residual diseases are required. One approach is to activate
      tumor-specific cytotoxic T cells with dendritic cells loaded with tumor cells. In
      order to enhance their immunogenicity, ovarian tumor cells (SK-OV-3, which
      express two well-characterized antigens HER-2/neu and MUC-1) were killed by
      oxidation with hypochlorous acid (HOCl). RESULTS: Treatment for 1 h with 60
      microM HOCl was found to induce necrosis in all SK-OV-3 cells. Oxidized, but not
      live, SK-OV-3 was rapidly taken up by monocyte-derived dendritic cells, and
      induced partial dendritic cell maturation. Dendritic cells cultured from HLA-A2
      healthy volunteers were loaded with oxidized SK-OV-3 (HLA-A2-) and co-cultured
      with autologous T cells. Responding T cells were tested for specificity after a
      further round of antigen stimulation. In ELISPOT assays, T cells produced
      interferon-gamma (IFN-gamma) in response to the immunizing cellular antigen, and
      also to peptides coding for MUC-1 and HER-2/neu HLA-A2 restricted epitopes,
      demonstrating efficient cross-presentation of cell-associated antigens. In
      contrast, no responses were seen after priming with heat-killed or HCl-killed SK
      OV-3, indicating that HOCl oxidation and not cell death/necrosis per se enhanced
      the immunogenicity of SK-OV-3. Finally, T cells stimulated with oxidized SK-OV-3
      showed no cross-reaction to oxidized melanoma cells, nor vice versa,
      demonstrating that the response was tumor-type specific. CONCLUSIONS:
      Immunization with oxidized ovarian tumor cell lines may represent an improved
      therapeutic strategy to stimulate a polyclonal anti-tumor cellular immune
      response and hence extend remission in ovarian cancer.

PMID- 16463040
TI  - Conversion of intermittent exotropia types subsequent to part-time occlusion
      therapy and its sustainability.
AB  - PURPOSE: To evaluate the effects of part-time occlusion therapy on types of
      intermittent exotropia and sustainability of converted types. METHODS: Forty-four
      and 26 children with basic-type and convergence-insufficiency-type intermittent
      exotropia, respectively, were evaluated in this study. Upon initial examination,
      we obtained both distant and near deviating angles using prism cover tests, after
      correcting for refractive errors. We conducted occlusion of the nondeviating eye
      for 3 months at 3 h/day and assessed the changes in types of intermittent
      exotropia. We also observed the changes of deviating angles and sustainability of
      types after 3 months of cessation of part-time occlusion in patients who did not
      undergo surgery. RESULTS: Preocclusion deviating angles (mean +/- SD) were
      determined to be 27.1+/-7.46 prism diopters (PD) on distant measurements and
      30.6+/-7.92 PD on near measurements. After 3 months of occlusion, the deviating
      angles were 25.9+/-9.10 PD on distant measurements and 21.4+/-11.00 PD on near
      measurements, corresponding to a significant reduction (p=0.005 and p<0.001,
      respectively). Fourteen patients (32%) suffering from basic type of intermittent
      exotropia converted to the pseudodivergence excess type. In patients suffering
      from the basic type who exhibited no changes in type, 9 patients (20%) exhibited
      reductions on both near and distant angle measurements. Among the convergence
      insufficiency type of patients, 18 (69%) converted to basic type and 2 patients
      (7%) converted to the pseudodivergence excess type. In the 15 patients who did
      not undergo surgery, the converted types were maintained in 6 patients, though
      the other 9 patients showed regression to the prepatching types after cessation
      of patching for 3 months. CONCLUSION: Part-time occlusion therapy resulted in the
      conversion of the basic and convergence insufficiency types to pseudodivergence
      excess and basic types in more than half of the intermittent exotropes. Future
      studies on correlation between type conversion and surgical outcome would be
      necessary.

PMID- 16463042
TI  - Control of MAPK signaling specificity by a conserved residue in the MEK-binding
      domain of the yeast scaffold protein Ste5.
AB  - The yeast kinase scaffold Ste5 has been proposed to prevent unwanted cross-talk
      between the pheromone response pathway and other MAPK cascades. Protein fusion
      experiments have demonstrated that covalently tethering signaling components to
      each other or to Ste5 can determine the outcome of signaling. However, these do
      not fully test the role of scaffolds in signaling specificity, since fusing
      components precludes differential dissociation of subpopulations. We performed a
      targeted genetic screen on STE5 and repeatedly identified recessive mutations in
      a conserved residue, E756, in the Ste7/MEK-binding domain that caused erroneous
      activation of the filamentation MAPK pathway by pheromone signaling. Mutant cells
      exhibited a shift in the MAPK activation pattern such that the filamentation MAPK
      Kss1 was predominately activated in response to pheromone. Velocity sedimentation
      studies showed that the mutant scaffold was defective in binding to a
      phosphorylated subpopulation of Ste7. Our data suggest that increased
      dissociation of activated Ste7 kinase from the mutant scaffold may cause the
      observed shift in MAPK activation from Fus3 to Kss1 and the resulting loss of
      specificity. Cross-talk in ste5-E756G cells was due to both increased activation
      of Kss1 and reduced Fus3-dependent degradation of the filamentation pathway
      transcription factor Tec1. These studies demonstrate a role for an endogenous
      scaffold in signaling specificity.

PMID- 16463041
TI  - Spatiotemporal expression of duplicate AGAMOUS orthologues during floral
      development in Phalaenopsis.
AB  - The AGAMOUS (AG) family of MADS-box genes plays important roles in controlling
      the development of the reproductive organs of flowering plants. To understand the
      molecular mechanisms behind the floral development in the orchid, we isolated and
      characterized two AG-like genes from Phalaenopsis that we denoted PhalAG1 and
      PhalAG2. Phylogenetic analysis indicated that PhalAG1 and PhalAG2 fall into
      different phylogenetic positions in the AG gene family as they belong to the C-
      and D-lineages, respectively. Reverse transcription-polymerase chair reaction (RT
      PCR) analyses showed that PhalAG1 and PhalAG2 transcripts were detected in flower
      buds but not in vegetative organs. Moreover, in situ hybridization experiments
      revealed that PhalAG1 and PhalAG2 hybridization signals were observed in the lip,
      column, and ovule during the floral development of Phalaenopsis, with little
      difference between the expression patterns of the two genes. These results
      suggest that both AG-like genes in Phalaenopsis act redundantly with each other
      in floral development.

PMID- 16463043
TI  - Effect of a 12-month physical conditioning programme on the metabolic cost of
      walking in healthy older adults.
AB  - The metabolic cost of walking (C(W)) is increased in healthy older adults.
      Previously, this has been suggested to be associated with age-related decline in
      physiological/functional factors such as stability and muscle size and strength.
      Physical training can improve such factors as well as aspects of gait performance
      in older adults. The aim of this investigation was to determine if it also has a
      beneficial impact on (lowers) C(W). Thirty-eight community dwelling older adults
      (aged 70-82 years) assigned to a training group (TRA, n=25) or a control group
      (CON, n=13) participated in a 12-month intervention. TRA followed a multi
      component physical conditioning programme involving supervised resistance,
      aerobic, and balance exercises twice per week. They also undertook home based
      exercises once per week. CON carried on with their normal daily activities. C(W)
      and indicators of functional capacity (knee extensor isometric strength, single
      leg balance time, sit and reach, stand and reach, and 6 min walk distance) were
      assessed prior to and following the intervention. Significant improvements in
      knee extensor isometric strength (+21%), single leg balance time (+30%), and 6
      min walk distance (+6%) were observed in TRA (P<0.05) but not in CON. However, no
      change in C(W) was observed. In conclusion, this investigation has shown that a
      multi-component physical conditioning programme had a beneficial impact on
      functional capacity but did not lower C(W) in healthy community dwelling older
      adults.

PMID- 16463044
TI  - The energy cost of cycling in young obese women.
AB  - In order to evaluate the difference in the energy cost of submaximal cycling
      between normal weight (NW) and obese (OB) females, nine OB (age 23.2 years+/-1.6
      SE, BMI 40.4+/-1.2 kg/m2) and nine NW (age 25.6 years+/-1.8, BMI 21.7+/-0.6
      kg/m2) healthy young women were studied during a graded bicycle ergometer test at
      40, 60, 80, 100 and 120 W. At rest and at all workloads, oxygen uptake VO2 was
      higher in OB than in NW women (Student's t test, P<0.05-0.01), as well as
      respiratory quotient during all exercise levels (P<0.05-0.01), while similar
      values of heart rate, pulmonary ventilation and breathing efficiency were found
      between the two groups. Maximal VO2 and anaerobic threshold were higher in OB
      women, and they also explained the higher oxygen pulse observed during submaximal
      exercise, but no difference was found when the values were adjusted for fat-free
      mass. While net mechanical efficiency (ME) was significantly lower in OB (ANOVA,
      P<0.05), delta ME was similar in both groups, indicating no substantial
      derangement of muscle intrinsic efficiency in obesity, but suggesting that the
      increased mass of body segments involved in cycling movements may be chiefly
      responsible for the higher energy cost of this type of exercise. Comparison of
      the actual VO2 presently measured with that predicted by available cycle
      ergometry equations at the different workloads indicated inaccuracy of various
      degrees ranging from 8.4 to -31.9%. It is concluded that the lower mechanical
      efficiency displayed by obese women in cycling has to be taken into account when
      prescribing exercise through methods predicting the metabolic load.

PMID- 16463045
TI  - Meta-analysis of the relationship between alcohol consumption and coronary heart
      disease and mortality in type 2 diabetic patients.
AB  - AIMS/HYPOTHESIS: This systematic review examines the relationship between alcohol
      consumption and long-term complications of type 2 diabetes. Meta-analyses could
      only be performed for total mortality, mortality from CHD, and CHD incidence,
      because the availability of articles on other complications was too limited.
      MATERIALS AND METHODS: A PubMed search through to September 2005 was performed
      and the reference lists of relevant articles examined. Among the relevant
      articles there were six cohort studies reporting on the risk of total mortality
      and/or fatal and/or incident CHD in alcohol non-consumers and in at least two
      groups of alcohol consumers. RESULTS: Statistical pooling showed lower risks in
      alcohol consumers than in non-consumers (the reference category). The relative
      risk (RR) of total mortality was 0.64 (95% CI 0.49-0.82) in the <6 g/day
      category. In the higher alcohol consumption categories (6 to <18, and > or =18
      g/day), the RRs of total mortality were not significant. Risks of fatal and total
      CHD were significantly lower in all three categories of alcohol consumers (<6, 6
      to <18 and > or =18 g/day) than in non-consumers, with RRs ranging from 0.34 to
      0.75. CONCLUSIONS/INTERPRETATION: This meta-analysis shows that, as with findings
      in the general population, moderate alcohol consumption is associated with a
      lower risk of mortality and CHD in type 2 diabetic populations.

PMID- 16463046
TI  - Overproduction of large VLDL particles is driven by increased liver fat content
      in man.
AB  - AIMS/HYPOTHESIS: We determined whether hepatic fat content and plasma adiponectin
      concentration regulate VLDL(1) production. METHODS: A multicompartment model was
      used to simultaneously determine the kinetic parameters of triglycerides (TGs)
      and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of
      [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18
      non-diabetic men. Liver fat content was determined by proton spectroscopy and
      intra-abdominal fat content by MRI. RESULTS: Univariate regression analysis
      showed that liver fat content, intra-abdominal fat volume, plasma glucose,
      insulin and HOMA-IR (homeostasis model assessment of insulin resistance)
      correlated with VLDL(1) TG and ApoB production. However, only liver fat and
      plasma glucose were significant in multiple regression models, emphasising the
      critical role of substrate fluxes and lipid availability in the liver as the
      driving force for overproduction of VLDL(1) in subjects with type 2 diabetes.
      Despite negative correlations with fasting TG levels, liver fat content, and
      VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB
      production and thus was not a predictor of VLDL(1) production. However,
      adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB.
      CONCLUSIONS/INTERPRETATION: We propose that the metabolic effect of insulin
      resistance, partly mediated by depressed plasma adiponectin levels, increases
      fatty acid flux from adipose tissue to the liver and induces the accumulation of
      fat in the liver. Elevated plasma glucose can further increase hepatic fat
      content through multiple pathways, resulting in overproduction of VLDL(1)
      particles and leading to the characteristic dyslipidaemia associated with type 2
      diabetes.

PMID- 16463047
TI  - Evidence that oestrogen receptor-alpha plays an important role in the regulation
      of glucose homeostasis in mice: insulin sensitivity in the liver.
AB  - AIMS/HYPOTHESIS: We used oestrogen receptor-alpha (ERalpha) knockout (ERKO) and
      receptor-beta (ERbeta) knockout (BERKO) mice to investigate the mechanism(s)
      behind the effects of oestrogens on glucose homeostasis. METHODS: Endogenous
      glucose production (EGP) was measured in ERKO mice using a euglycaemic
      hyperinsulinaemic clamp. Insulin secretion was determined from isolated islets.
      In isolated muscles, glucose uptake was assayed by using radiolabelled isotopes.
      Genome-wide expression profiles were analysed by high-density oligonucleotide
      microarray assay, and the expression of the genes encoding steroyl-CoA desaturase
      and the Leptin receptor (Scd1 and Lepr, respectively) was confirmed by RT-PCR.
      RESULTS: ERKO mice had higher fasting blood glucose, plasma insulin levels and
      IGT. The plasma leptin level was increased, while the adiponectin concentration
      was decreased in ERKO mice. Levels of both glucose- and arginine-induced insulin
      secretion from isolated islets were similar in ERKO and wild-type mice. The
      euglycaemic-hyperinsulinaemic clamp revealed that suppression of EGP by increased
      insulin levels was blunted in ERKO mice, which suggests a pronounced hepatic
      insulin resistance. Microarray analysis revealed that in ERKO mice, the genes
      involved in hepatic lipid biosynthesis were upregulated, while genes involved in
      lipid transport were downregulated. Notably, hepatic Lepr expression was
      decreased in ERKO mice. In vitro studies showed a modest decrease in insulin
      mediated glucose uptake in soleus and extensor digitorum longus (EDL) muscles of
      ERKO mice. BERKO mice demonstrated normal glucose tolerance and insulin release.
      CONCLUSIONS/INTERPRETATION: We conclude that oestrogens, acting via ERalpha,
      regulate glucose homeostasis mainly by modulating hepatic insulin sensitivity,
      which can be due to the upregulation of lipogenic genes via the suppression of
      Lepr expression.

PMID- 16463049
TI  - Diversity of centromeric repeats in two closely related wild rice species, Oryza
      officinalis and Oryza rhizomatis.
AB  - Oryza officinalis (CC, 2n = 24) and Oryza rhizomatis (CC, 2n = 24) belong to the
      Oryza genus, which contains more than 20 identified wild rice species. Although
      much has been known about the molecular composition and organization of
      centromeres in Oryza sativa, relatively little is known of its wild relatives. In
      the present study, we isolated and characterized a 126-bp centromeric satellite
      (CentO-C) from three bacterial artificial chromosomes of O. officinalis. In
      addition to CentO-C, low abundance of CentO satellites is also present in O.
      officinalis. In order to determine the chromosomal locations and distributions of
      CentO-C (126-bp), CentO (155 bp) and TrsC (366 bp) satellite within O.
      officinalis, fluorescence in situ hybridization examination was done on pachytene
      or metaphase I chromosomes. We found that only ten centromeres (excluding
      centromere 7 and 2) contain CentO-C arrays in O. officinalis, while centromere 7
      comprises CentO satellites, and centromere 2 is devoid of any detectable
      satellites. For TrsC satellites, it was detected at multiple subtelomeric regions
      in O. officinalis, however, in O. rhizomatis, TrsC sequences were detected both
      in the four centromeric regions (CEN 3, 4, 10, 11) and the multiple subtelomeric
      regions. Therefore, these data reveal the evolutionary diversification pattern of
      centromere DNA within/or between close related species, and could provide an
      insight into the dynamic evolutionary processes of rice centromere.

PMID- 16463048
TI  - Gemfibrozil decreases atherosclerosis in experimental diabetes in association
      with a reduction in oxidative stress and inflammation.
AB  - AIMS/HYPOTHESIS: It is postulated that peroxisome proliferator-activated receptor
      alpha agonists confer cardiovascular benefits in diabetes, independently of their
      effects on lipid metabolism. We investigated putative mechanisms responsible for
      these anti-atherogenic effects in an in vivo model of diabetes-associated
      atherosclerosis. MATERIALS AND METHODS: Control and streptozotocin-induced
      diabetic apolipoprotein-deficient mice received gemfibrozil (100 mg kg(-1) day(
      1)) or no treatment for 20 weeks. Aortic plaque deposition was assessed by Sudan
      IV staining and subsequent en face quantification. Superoxide production was
      measured using lucigenin-enhanced chemiluminescence. Markers of pathways
      including inflammation and oxidative stress were measured using real-time RT-PCR.
      RESULTS: No significant effect of gemfibrozil was observed on glycated
      haemoglobin, cholesterol or insulin in diabetic mice. Diabetes was associated
      with a three-fold increase in plaque area and a significant increase in NADPH
      dependent superoxide compared with control mice. Gemfibrozil significantly
      attenuated plaque area and superoxide production in diabetic mice. In addition,
      gemfibrozil reduced the expression of the genes encoding the NADPH oxidase
      subunits p47phox, gp91phox and Rac-1. In addition, gemfibrozil reduced the
      expression of the genes encoding nuclear factor kappa B (NF-kappaB) subunit, p65,
      the NF-kappaB-dependent chemokine monocyte chemoattractant protein-1, and tissue
      factor. CONCLUSIONS/INTERPRETATIONS: This study demonstrates that gemfibrozil
      exerts anti-atherogenic actions, independently of changes in cholesterol and
      glucose metabolism. Such findings emphasise the possible usefulness of fibrates
      such as gemfibrozil in a setting of atherosclerosis even in the absence of
      dyslipidaemia.

PMID- 16463050
TI  - [Norovirus infections in Germany].
AB  - Noroviruses are responsible for the majority of acute viral gastroenteritis
      infections worldwide. Transmission may be faecal-oral or through contaminated
      food and water or airborne by virus-containing aerosols. Characteristics of
      noroviruses that facilitate their spread are their high concentration in stool
      and vomitus, their extreme environmental stability, their low infectious dose as
      well as the lack of long-lasting immunity. The majority of norovirus infections
      occur in large outbreaks among persons living in institutional settings, such as
      hospitals and nursing homes, although sporadic cases also occur. Children and
      elderly persons are most often affected. Illness is characterized by acute onset
      of projectile vomiting. For prevention and control of norovirus outbreaks strict
      control management is necessary. Based on the high genomic variability new
      variant noroviruses with different pathogenic factors can arise. Depending on the
      circulating variant the extent of the usual winter peak can vary enormously.
      Available diagnostic methods include RT-PCR assays for detection of viral RNA,
      electron microscopy and enzyme immunoassays (EIA) for detection of viral
      antigens. The implicated virus can be subtyped through nucleotide sequencing and
      linked to a specific outbreak. With the enactment of the Protection against
      Infection Act in January 2001 a mandatory reporting system of norovirus
      infections was established. Analysis of surveillance data from this system
      permits a detailed overview of the nationwide epidemiology of this disease in
      Germany.

PMID- 16463052
TI  - Treatment of HCV infection with interferon alpha-2b and ribavirin in a patient
      with X-linked lymphoproliferative syndrome.
AB  - Chronic hepatitis C (HCV) infection in patients with primary immunodeficiency
      increases the risk of an accelerated progression of HCV-related liver disease.
      Here, we report a patient with X-linked lymphoproliferative syndrome infected
      with HCV and Epstein-Barr virus (EBV). After combination treatment with
      interferon alpha-2b and ribavirin, clearance of HCV-RNA was achieved, and
      noteworthily, EBV DNA also became undetectable.

PMID- 16463051
TI  - Monitoring expression profiles of Arabidopsis genes during cold acclimation and
      deacclimation using DNA microarrays.
AB  - A comparative analysis of gene expression profiles during cold acclimation and
      deacclimation is necessary to elucidate the molecular mechanisms of cold stress
      responses in higher plants. We analyzed gene expression profiles in the process
      of cold acclimation and deacclimation (recovery from cold stress) using two
      microarray systems, the 7K RAFL cDNA microarray and the Agilent 22K
      oligonucleotide array. By both microarray analyses, we identified 292 genes up
      regulated and 320 genes down-regulated during deacclimation, and 445 cold up
      regulated genes and 341 cold down-regulated genes during cold acclimation. Many
      genes up-regulated during deacclimation were found to be down-regulated during
      cold acclimation, and vice versa. The genes up-regulated during deacclimation
      were classified into (1) regulatory proteins involved in further regulation of
      signal transduction and gene expression and (2) functional proteins involved in
      the recovery process from cold-stress-induced damages and plant growth. We also
      applied expression profiling studies to identify the key genes involved in the
      biosynthesis of carbohydrates and amino acids that are known to play important
      roles in cold acclimation. We compared genes that are regulated during
      deacclimation with those regulated during rehydration after dehydration to
      discuss the similarity and difference of each recovery process.

PMID- 16463053
TI  - The effect of calcium channel blockers on stone regrowth and recurrence after
      shock wave lithotripsy.
AB  - We evaluated the possible effects of a calcium entry blocking agent "verapamil"
      on new stone formation and/or regrowth of residual fragments after shock wave
      lithotripsy (SWL) during long-term follow-up (>30 months) and compared the
      results with the success rates of adequate fluid intake. A total of 70 patients
      treated with SWL were randomly divided into three different groups, in the first
      two of which the patients received different preventive measures with respect to
      stone recurrence and/or regrowth. While 25 patients received a calcium channel
      blocking agent, verapamil hydrochloride, beginning 3 days before SWL and
      continued 4 weeks after the procedure, an additional 25 patients were put in an
      enforced fluid intake program and the remaining 20 patients received no specific
      medication and/or measure apart from close follow-up. Patients were followed
      regularly with respect to the clearance/regrowth of the residual fragments and
      that of new stone formation during long-term follow-up (within a mean follow-up
      of 30.4 months). The overall stone recurrence rate was 14% (10/70). Of the
      patients who became stone free (12/25, 48%) in group I, only one patient (1/12,
      8.3%) showed a new stone formation during long-term follow-up. The figure was 40%
      (4/10) in group II patients and 55% (5/9) in group III patients receiving no
      specific medication. Regarding the residual stone fragments (<5 mm) after SWL,
      again high fluid intake was found to be the most effective on stone regrowth
      rates (2/13, 15.3%). Patients treated with verapamil also had acceptable regrowth
      rates (3/15, 20%). Finally, verapamil treatment significantly improved the
      clearance of residual fragments; while 7 out of 15 patients with residual
      fragments passed these particles successfully, (46.5%) in this group; these
      figures were 46% (6/13) and 18% (2/13) in the remaining groups. Residual
      fragments located in lower calyces demonstrated a poor clearance rate with higher
      regrowth rates. Verapamil administration was found to be effective enough to
      limit the regrowth of residual fragments and also to facilitate residual fragment
      clearance after SWL. Patients receiving this medication seemed to pass the
      retained fragments easily in a shorter time than the others.

PMID- 16463054
TI  - Nicotine psychopharmacology research contributions to United States and global
      tobacco regulation: a look back and a look forward.
AB  - Nicotine has a long and storied history in physiology and pharmacology.
      Historically, it has been used as a tool to explore the nervous system, studied
      for its role in tobacco use, and more recently examined for its diverse potential
      medicinal uses. Psychopharmacology research has been pivotal in the science
      foundation for nicotine and tobacco product regulation.

PMID- 16463055
TI  - Nicotine place preference in the mouse: influences of prior handling, dose and
      strain and attenuation by nicotinic receptor antagonists.
AB  - RATIONALE: Although conditioned place preferences (CPPs) are seen with most
      abused drugs, nicotine does not always produce a preference in this design.
      OBJECTIVES: The goals of the present experiment were to (1) examine various
      factors that could contribute to these inconsistent results and (2) begin to
      evaluate the specific nicotinic receptors involved in the nicotine CPP. METHODS:
      The influences of prior handling, environmental habituation, and injection
      habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently,
      various nicotine doses were assessed for their abilities to produce a CPP, and
      the effectiveness of nicotinic receptor antagonists in attenuating this
      preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and
      DBA/2J mice to examine the influence of strain in this design. RESULTS: Nicotine
      CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR
      mice. Habituation to the injection techniques failed to strengthen the
      preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine.
      This CPP was attenuated by mecamylamine and dihydro-beta-erythroidine (DHbetaE).
      A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. CONCLUSION:
      Earlier handling experience and strain are important factors when evaluating a
      nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the
      nicotine CPP, indicating that this model can elucidate underlying mediators of
      nicotine reward.

PMID- 16463056
TI  - Woody debris contribution to the carbon budget of selectively logged and maturing
      mid-latitude forests.
AB  - Woody debris (WD) is an important component of forest C budgets, both as a C
      reservoir and source of CO2 to the atmosphere. We used an infrared gas analyzer
      and closed dynamic chamber to measure CO(2) efflux from downed coarse WD (CWD;
      diameter>or=7.5 cm) and fine WD (FWD; 7.5 cm>diameter>or=2 cm) to assess
      respiration in a selectively logged forest and a maturing forest (control site)
      in the northeastern USA. We developed two linear regression models to predict WD
      respiration: one based on WD temperature, moisture, and size (R2=0.57), and the
      other on decay class and air temperature (R2=0.32). WD respiration (0.28+/-0.09
      Mg C ha-1 year-1) contributed only approximately 2% of total ecosystem
      respiration (12.3+/-0.7 Mg C ha-1 year-1, 1999-2003), but net C flux from CWD
      accounted for up to 30% of net ecosystem exchange in the maturing forest. C flux
      from CWD on the logged site increased modestly, from 0.61+/-0.29 Mg C ha-1 year-1
      prior to logging to 0.77+/-0.23 Mg C ha-1 year-1 after logging, reflecting
      increased CWD stocks. FWD biomass and associated respiration flux were
      approximately 7 times and approximately 5 times greater, respectively, in the
      logged site than the control site. The net C flux associated with CWD, including
      inputs and respiratory outputs, was 0.35+/-0.19 Mg C ha-1 year-1 (net C sink) in
      the control site and -0.30+/-0.30 Mg C ha-1 year-1 (net C source) in the logged
      site. We infer that accumulation of WD may represent a small net C sink in
      maturing northern hardwood forests. Disturbance, such as selective logging, can
      enlarge the WD pool, increasing the net C flux from the WD pool to the atmosphere
      and potentially causing it to become a net C source.

PMID- 16463057
TI  - Effect of hybridization of the Quercus crassifolia x Quercus crassipes complex on
      the community structure of endophagous insects.
AB  - In a previous study, we showed that the geographic proximity of hybrid plants to
      the allopatric areas of parental species increases their morphological and
      genetic similarity with them. In the present work, we explored whether the
      endophagous fauna of hybrid plants show the same pattern. We studied the canopy
      species richness, diversity and composition of leaf-mining moths (Lepidoptera:
      Tischeridae, Citheraniidae) and gall-forming wasps (Hymenoptera: Cynipidae)
      associated with two species of red oaks (Quercus crassifolia and Quercus
      crassipes) and their interspecific hybrid (Quercusxdysophylla Benth pro sp.) in
      seven hybrid zones in central Mexico, during four seasons in 2 years. The study
      was conducted on 194 oak trees with known genetic status [identified by leaf
      morphology and molecular markers (random amplified polymorphic DNAs)], and the
      results indicate a bidirectional pattern of gene flow. Hybrid plants supported
      intermediate levels of infestation of gall-forming and leaf-mining insects
      compared to their putative parental species. The infestation level of leaf-mining
      insects varied significantly following the pattern: Q. crassifolia>hybrids>Q.
      crassipes, whereas the gall-forming insects showed an inverse pattern. A negative
      and significant relationship was found between these two types of insect guilds
      in each host taxa, when the infestation percentage was evaluated. It was found
      that 31.5% (n=11) of the endophagous insects were specific to Q. crassipes, 22.9%
      (n=8) to Q. crassifolia, and 8.6% (n=3) to hybrid individuals. The hybrid bridge
      hypothesis was supported in the case of 25.7% (n=9) of insects, which suggests
      that the presence of a hybrid intermediary plant may favor a host herbivore shift
      from one plant species to another. Greater genetic diversity in a hybrid zone is
      associated with greater diversity in the endophagous community. The geographic
      proximity of hybrid plants to the allopatric site of a parental species increases
      their similarity in terms of endophagous insects and the Eje Neovolcanico acts as
      a corridor favoring this pattern.

PMID- 16463058
TI  - Gemcitabine resistance due to deoxycytidine kinase deficiency can be reverted by
      fruitfly deoxynucleoside kinase, DmdNK, in human uterine sarcoma cells.
AB  - PURPOSE: Cytotoxic nucleoside analogues are widely used in the treatment of
      cancers. Resistance to these compounds is frequent and often multifactorial.
      Deficiency in deoxycytidine kinase (dCK), the rate-limiting activating enzyme,
      has been reported in a number of in vitro models as well as in various clinical
      situations. Some strategies to overcome this mechanism of resistance have been
      proposed there by gene transfer based therapy. METHODS: We have developed and
      characterized a gemcitabine-resistant cell line (Messa 10 K) from the human
      uterine sarcoma Messa strain, and transfected this cell line with the
      multisubstrate deoxynucleoside kinase from Drosophila melanogaster (DmdNK) in
      order to revert the resistance in Messa 10 K cells which was due to dCK
      deficiency. RESULTS: Messa 10 K is highly resistant to gemcitabine (122-fold),
      troxacitabine (>15-fold) and araC (13,556-fold). Quantitative real-time PCR and
      western blot analysis showed that dCK was not detectable in Messa 10 K cells,
      presumably because of a genetic modification. The transfection of Messa 10 K
      cells with DmdNK significantly increased the sensitivity to gemcitabine.
      CONCLUSIONS: These results show that genetic modifications in non-hematological
      malignant cells may be associated with resistance to gemcitabine, and that the
      gene transfer of non-human genes can be used for the reversion of nucleoside
      analogue resistance due to dCK deficiency.

PMID- 16463059
TI  - A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy
      in patients with esophageal cancer.
AB  - PURPOSE: To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum
      (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in
      the treatment of esophageal cancer. The purpose of the phase II trial is to
      determine efficacy and further define the side effect profile. METHODS: Twenty
      six patients with clinical stage I to IVA squamous cell carcinoma of the
      esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of
      fluorouracil (400 mg/m2 administered as continuous intravenous infusion on days 1
      5 and days 8-12) plus escalating doses of nedaplatin (40 mg/m2 in level 1, 50
      mg/m2 in level 2, or 60 mg/m2 in level 3 on days 1 and 8), repeated twice every 3
      weeks with concurrent radiotherapy (60 Gy). RESULTS: Between July 1998 and
      February 2004, a total of 26 patients entered this trial, all of whom were
      considered evaluable for toxicity assessment. In phase I of the study, 12
      patients were treated in sequential cohorts of three to six patients per dose
      level. The maximum tolerated dose was reached at level 3 with two grade 4
      neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing
      schedule is level 2. Of the 20 patients treated at the RD level 2, including 6
      patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3-4
      neutropenia, 5 patients (25.0%) had grade 3-4 thrombocytopenia, 4 patients
      (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3-4 esophagitis.
      Other toxicities were relatively mild and usually of grade 2 or less. Objective
      responses were noted in the 26 patients (overall response rate, 88.5%) including
      11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and
      37.2%, respectively, with a median survival time of 21.2 months. CONCLUSIONS: The
      combination of nedaplatin and 5-FU with radiation is a feasible regimen that
      shows promising antitumor activity with an acceptable safety profile in patients
      with esophageal cancer.

PMID- 16463060
TI  - Phase I and pharmacokinetic study of weekly NV06 (Phenoxodiol), a novel isoflav-3
      ene, in patients with advanced cancer.
AB  - BACKGROUND: We wished to define the maximum tolerated dose (MTD), toxicity, and
      pharmacokinetics of the novel isoflav-3-ene, NV06 (Phenoxodioltrade mark), a
      compound with a diphenolic structure related chemically and biologically to
      genistein and flavopiridol. PATIENTS AND METHODS: Twenty-one patients with
      advanced cancers were treated with weekly intravenous administration of NV06 at
      escalating dose levels with 1-4 patients at each dose cohort. Plasma sampling was
      undertaken to characterize the pharmacokinetic (PK) profile of the compound.
      RESULTS: Toxicity was minimal, with asymptomatic Grade 3 lymphocytopenia
      occurring in nine patients. Nine patients developed Grade 1 nausea, six patients
      developed Grade 1 increases in alkaline phosphatase, and six patients developed
      Grade 1 increases in transaminases. Two patients experienced hypersensitivity
      reactions. The MTD was not reached. Most patients had progressive disease on
      treatment but eight completed 12 weeks and two completed 24 weeks of treatment.
      The best response was stable disease of 6 months duration. The plasma half-life
      (T1/2), clearance (Cl), and volume of distribution (VD) were 304 (+/-91) min, 82
      (+/-19) ml/min and 32,663 (+/-7,199) ml, respectively, for total NV06.
      CONCLUSIONS: NV06 is well tolerated and can be given safely as an intravenous
      infusion over 1-2 h at a dose of at least 30 mg/kg.

PMID- 16463061
TI  - A phase I trial of carboplatin and etoposide for elderly (>or=75 year-old)
      patients with small-cell lung cancer.
AB  - PURPOSE: The combination of carboplatin and etoposide is currently considered the
      most appropriate regimen for treating elderly patients with small-cell lung
      cancer (SCLC). Previous reports on elderly patients, 70 years or older, found
      that the recommended dose was close to that of younger patients. Then, we
      conducted a phase I study of carboplatin and etoposide in elderly patients, 75
      years or older, with SCLC. This study aimed to determine the maximum tolerated
      dose (MTD) and dose-limiting toxicity (DLT). METHODS: Twenty-six patients
      fulfilling the eligibility criteria, chemotherapy-naive, performance status (PS)
      of 0-2, age>or=75, and adequate organ functions were enrolled. Patients'
      characteristics were: male/female=21/5; PS 0/1/2=9/11/6; median age (range)=78
      (75-82); and limited/extensive stage=16/10. The patients intravenously received
      carboplatin with a target AUC of 4 or 5 mg min/ml (Chatelut formula) on day 1 and
      etoposide at 80-120 mg/m2 on days 1, 2 and 3. Therapy was repeated four times in
      every 4 weeks. RESULTS: The MTD of carboplatin/etoposide was AUC=5/80, 4/110, and
      4/120. The DLTs were thrombocytopenia, neutropenia, leukopenia, and febrile
      neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (>or=4 days),
      leukopenia (>or=4 days), and febrile neutropenia occurred in 27, 20, 7, and 13%
      of cases at MTD levels, respectively, and 0% at other levels. Twenty of 26
      patients showed objective responses (2CR, 18PR; RR=77%). CONCLUSION: A dose of
      carboplatin of AUC=4 and etoposide of 100 mg/m2 was recommended in this regimen.

PMID- 16463062
TI  - Advanced backcross QTL analysis of a hard winter wheat x synthetic wheat
      population.
AB  - Advanced backcross quantitative trait locus (AB-QTL) analysis was used to
      identify QTLs for yield and yield components in a backcross population developed
      from a cross between hard red winter wheat (Triticum aestivum L.) variety Karl 92
      and the synthetic wheat line TA 4152-4. Phenotypic data were collected for
      agronomic traits including heading date, plant height, kernels per spike, kernel
      weight, tiller number, biomass, harvest index, test weight, grain yield, protein
      content, and kernel hardness on 190 BC2F(2:4) lines grown in three replications
      in two Kansas environments. Severity of wheat soil-borne mosaic virus (WSBMV)
      reaction was evaluated at one location. The population was genotyped using 151
      microsatellite markers. Of the ten putative QTLs identified, seven were located
      on homologous group 2 and group 3 chromosomes. The favorable allele was
      contributed by cultivated parent Karl 92 at seven QTLs including a major one for
      WSBMV resistance, and by the synthetic parent at three QTLs: for grain hardness,
      kernels per spike, and tiller number.

PMID- 16463063
TI  - Do pesticides cause childhood cancer?
AB  - OBJECTIVES: Epidemiological studies have reported associations between childhood
      cancer and either parental or child exposure to pesticides. Reviews have been
      published in 1997 and 1998, where the evidence was found suggestive but not
      conclusive. An update of the current state of knowledge is warranted. METHODS: A
      literature search has been conducted to identify and evaluate new research
      results on this topic issued between 1998 and 2004. RESULTS: Eighteen new studies
      have been identified for this review. Collectively, the studies suggest an
      increase in the risk of different cancer types associated with exposure to
      pesticides. However, the evidence is conflicting with regard to cancer types as
      well as to causative factors across studies. The major shortcomings concern
      exposure assessment, where, e.g., "farming" is treated equal to "exposure to
      pesticides," disregarding other possible exposures, e.g., to biological or
      infectious agents, and hitherto unidentified lifestyle factors. Also, many
      exposure questionnaires used in case-control studies are based on broad and
      sometimes implausible categories. In most studies exposures were categorized as
      "ever vs. never," with no regard for exposure intensity or duration. CONCLUSIONS:
      The available literature does not allow firm conclusions with regard to
      pesticides and any type of childhood cancer. Investing in the acquisition and
      critical review of exposure information appears to be the crucial step for causal
      assessment in future research. However, focusing on the presence of pesticides,
      and not asking the question why they were used, might mask relevant associations
      to other causative agents.

PMID- 16463065
TI  - Cancer therapy-associated CNS neuropathology: an update and review of the
      literature.
AB  - Standard therapeutic options for brain tumors include surgery, radiation, and
      chemotherapy. Unfortunately, these same therapies pose risks of neurotoxicity,
      the most common long-term complications being radiation necrosis, chemotherapy
      associated leukoencephalopathy, and secondary neoplasms. These side effects
      remain difficult to predict, but are associated with risk factors that include
      patient age, therapeutic modality and dosage, genetic background, and
      idiosyncratic predispositions. Experimental treatments designed to enhance
      efficacy and to minimize neurotoxicity include molecularly targeted, genetic,
      stem cell, and immune therapies. Newer modifications in radiation and drug
      delivery include stereotactic radiosurgery, interstitial therapy such as
      intracavitary brachytherapy and gliadel wafer placement, 3D conformal radiation,
      boron neutron capture therapy, radiosensitizers, blood-brain barrier disrupting
      agents, and convection enhanced delivery. Toxicities associated with these newer
      modalities have yet to be fully investigated and documented. Additionally, a
      number of recently implemented radiographic techniques such as PET and SPECT
      imaging have enhanced the ability to distinguish recurrent tumor from radiation
      necrosis. Nevertheless, post-therapeutic brain biopsies and autopsies remain the
      gold standard for assessing neurotoxicity, therapeutic efficacy, tumor
      progression, and the development of secondary neoplasms. At the same time,
      treatment-associated changes such as tumor necrosis, vasculopathy, inflammation,
      and cytologic atypia can pose significant diagnostic pitfalls, particularly if
      the pathologist is not provided a detailed therapeutic history. Therefore, it is
      critical to recognize the full spectrum of cancer therapy-associated
      neuropathology, the topic of the current review.

PMID- 16463064
TI  - Pharyngeal pouch: associations and complications.
AB  - The aetiopathogenesis of pharyngeal pouch remains obscure. This review highlights
      the associations and complications of pharyngeal pouch to better understand the
      pathogenesis and management of the pouch. A search of the MEDLINE was conducted
      to identify studies that looked at associations and/or complications of the
      pharyngeal pouch. The Medical Subject Headings (MeSH) included Zenker's
      diverticulum and hypopharyngeal diverticulum. A total of 64 papers were included
      for the analysis. They consisted mainly of single case reports, case series and
      review articles and one case control study. A summary of evidence from the
      literature is discussed. This review shows the various associations and
      complications that can occur with pharyngeal pouches. It is important to be aware
      that pharyngeal pouch can co-exist with other pathologies and treatment needs to
      be altered to incorporate the treatment of the associated pathology too. Surgeons
      should also be aware of the complications that can occur within and outside the
      pouch.

PMID- 16463066
TI  - Intracellular calcium-binding protein S100A4 influences injury-induced migration
      of white matter astrocytes.
AB  - Astrocytes play a crucial role in central nervous system (CNS) pathophysiology.
      White and gray matter astrocytes are regionally specialized, and likely to
      respond differently to CNS injury and in CNS disease. We previously showed that
      the calcium-binding protein S100A4 is exclusively expressed in white matter
      astrocytes and markedly up-regulated after injury. Furthermore, down-regulation
      of S100A4 in vitro significantly increases the migration capacity of white matter
      astrocytes, a property, which might influence their function in CNS tissue
      repair. Here, we performed a localized injury (scratch) in confluent cultures of
      white matter astrocytes, which strongly express S100A4, and in cultures of white
      matter astrocytes, in which S100A4 was down-regulated by transfection with short
      interference (si) S100A4 RNA. We found that S100A4-silenced astrocytes rapidly
      migrated into the injury gap, whereas S100A4-expressing astrocytes extended
      hypertrophied processes toward the gap, but without closing it. To explore the
      involvement of S100A4 in migration of astrocytes in vivo, we induced focal
      demyelination and transient glial cell elimination in the spinal cord white
      matter by ethidium bromide injection in S100A4 (-/-) and (+/+) mice. The results
      show that astrocyte migration into the demyelinated area is promoted in S100A4 (
      /-) compared to (+/+) mice, in which a pronounced glial scar was formed. These
      data indicate that S100A4 reduces the migratory capacity of reactive white matter
      astrocytes in the injured CNS and is involved in glial scar formation after
      injury.

PMID- 16463067
TI  - Embryogenesis and seed development in Sinomanglietia glauca (Magnoliaceae).
AB  - The development of the floral bud, especially the ovule and seed coat, of
      Sinomanglietia glauca was observed. Floral buds were covered by eight to nine
      hypsophyll pieces. The hypsophyll nearest the tepal was closed completely and
      characterized by two arrays of densely stained cells with dense cytoplasm, which
      split longitudinally at flowering. The perianth consisted of 16 tepals arranged
      in three whorls. The gynoecium was composed of numerous apocarpous carpels; the
      ovule was anatropous with two integuments. Embryogenesis was of the Polygonum
      type, and the endosperm was nuclear. The inner integument degenerated during seed
      development. The seed of S. glauca had an endotestal seed coat comprised of a
      sclerotic layer derived from the inner adaxial epidermis of the outer integument
      and a sarcotesta derived mainly from the middle cells between the inner and outer
      epidermis of the outer integument. The embryo developed normally, so
      embryogenesis is not the cause of difficult regeneration.

PMID- 16463068
TI  - Vegetative reproduction and clonal diversity in Rhytidium rugosum (Rhytidiaceae,
      Bryopsida) inferred by morpho-anatomical and molecular analyses.
AB  - Many bryophytes exhibit specific life forms that result in the formation of
      distinct patches. This is primarily achieved by "consequent vegetative
      multiplication" through indeterminate growth and vegetative reproduction. Little,
      however, is known about the underlying mechanisms and genetic patterns. In this
      study on vegetative multiplication in bryophytes, we apply morpho-anatomical and
      molecular (AFLP fingerprinting) techniques to analyze the vegetative reproduction
      system, clonal diversity, and habitat colonization of a pleurocarpous moss,
      Rhytidium rugosum (Rhytidiaceae). Morpho-anatomically, three types of vegetative
      diaspores are identified and illustrated: ramets, separated after decay and
      disintegration of older shoot parts (clonal reproduction); brood
      branches/branchlets; and caducous shoot apices (both vegetative reproduction
      s.str.). The AFLP fingerprinting of 35 samples (from two plots in Thuringia,
      further German populations, and from France, Russia, and Canada) resulted in the
      identification of three clones from the two plots, each comprising two to 15
      samples with identical fingerprints. Samples from one clone occurred in both
      plots, thus proving dispersal of vegetative diaspores. The AFLP analysis further
      revealed close relationships of the plot samples, which suggest a clonal rather
      than generative (sexual) origin of the population.

PMID- 16463069
TI  - Relation of maternal low birth weight to infant growth retardation and
      prematurity.
AB  - OBJECTIVES: This study sought to determine the relationship between maternal
      birth weight, infant intrauterine growth retardation, and prematurity. METHODS:
      Stratified and logistic regression analyses were performed on a dataset of
      computerized Illinois vital records of African American (N = 61,849) and White (N
      = 203,698) infants born between 1989 and 1991 and their mothers born between 1956
      and 1975. RESULTS: Race-specific rates of small-for-gestational age (weight-for
      gestational age <10th percentile) and preterm (<37 weeks) infants rose as
      maternal birth weight declined. The adjusted (controlling for maternal age,
      education, marital status, parity, prenatal care utilization, and cigarette
      smoking) odds ratio (95% confidence interval) of small-for-gestational age for
      maternal low birth weight (<2,500 g) among African Americans and Whites were 1.7
      (1.1.4-1.9) and 1.8 (1.7-2.0), respectively. The adjusted odds ratio (95%
      confidence interval) of prematurity for maternal low birth weight (<2,500 g)
      among African Americans and Whites were 1.6 (1.3-1.9) and 1.3 (1.0-1.6),
      respectively. The racial disparity in the rates of small-for-gestational age and
      prematurity persisted independent of maternal birth weight: adjusted odds ratio
      equaled 2.2 (2.1-2.4) and 1.5 (1.4-1.7), respectively. CONCLUSIONS: Maternal low
      birth weight is a risk factor for infant intrauterine growth retardation and
      prematurity among African Americans independent of maternal risk status during
      pregnancy; it is a risk factor for infant intrauterine growth retardation among
      Whites. Maternal low birth weight fails to explain the racial disparity in the
      rates of small-for-gestational age and premature infants.

PMID- 16463070
TI  - The Inositol 1,4,5-triphosphate kinase1 gene affects olfactory reception in
      Drosophila melanogaster.
AB  - The Inositol 1,4,5-triphosphate (IP3) route is one of the two main transduction
      cascades that mediate olfactory reception in Drosophila melanogaster. The
      activity of IP3 kinase1 reduces the levels of this substrate by phosphorylation
      into inositol 1,3,4,5-tetrakiphosphate (IP4). We show here that the gene is
      expressed in olfactory sensory organs as well as in the rest of the head. To
      evaluate in vivo the olfactory functional effects of up-regulating IP3K1,
      individuals with directed genetic changes at the reception level only were
      generated using the UAS/Gal4 method. In this report, we described the
      consequences in olfactory perception of overexpressing the IP3Kinase1 gene at
      eight different olfactory receptor-neuron subsets. Six out of the eight studied
      Gal-4/UAS-IP3K1 hybrids displayed abnormal behavioral responses to ethyl acetate,
      acetone, ethanol or propionaldehyde. Specific behavioral defects corresponded to
      the particular neuronal olfactory profile. These data confirm the role of the
      IP3kinase1 gene, and consequently the IP3 transduction cascade, in mediating
      olfactory information at the reception level.

PMID- 16463072
TI  - Is sentinel lymph node biopsy appropriate in patients with thin melanomas: too
      early to tell?

PMID- 16463073
TI  - Validation of a breast cancer nomogram for predicting nonsentinel lymph node
      metastases after a positive sentinel node biopsy.
AB  - BACKGROUND: Although completion lymph node dissection (CLND) is the standard of
      care for breast cancer patients with sentinel lymph node (SLN) metastases, the
      SLN is the only node with tumor in 40% to 60% of cases. To assist with decision
      making regarding CLND, investigators at Memorial Sloan-Kettering Cancer Center
      devised and validated a nomogram for predicting the likelihood of non-SLN
      metastases. To assess the generalizable use of this nomogram, validation analysis
      was performed by using an external database. METHODS: Eight clinicopathologic
      variables for 200 consecutive breast cancer patients at the University of Texas
      M. D. Anderson Cancer Center with SLN metastases and CLND were entered into the
      nomogram. The accuracy of the nomogram to predict non-SLN metastases was assessed
      by the receiver operating characteristic (ROC) curve and linear regression
      analysis. The accuracy of the nomogram with touch-imprint cytology (TIC) as a
      substitute variable for frozen section was also evaluated. RESULTS: The linear
      correlation coefficient of the nomogram-predicted probabilities correlated with
      the observed incidence of non-SLN metastases for all patients (.97). The accuracy
      of the nomogram as measured by the area under the ROC curve was .71. When applied
      solely to patients who had TIC assessment of the SLN, the area under the ROC
      curve was .74. CONCLUSIONS: This study validated the Memorial Sloan-Kettering
      Cancer Center breast cancer nomogram by using an external database. TIC seems to
      be an acceptable substitute for frozen section as a nomogram variable. The
      nomogram may help predict an individual's risk of non-SLN metastases and assist
      in patient decision making regarding the benefit of CLND.

PMID- 16463071
TI  - Toward mapping daily challenges of living with ADHD: maternal and child
      perspectives using electronic diaries.
AB  - Attention-deficit/hyperactivity disorder (ADHD) has an impact on the family as
      well as the affected child. This study developed and tested an electronic diary
      for mapping the challenges of everyday family life in a sample of children with
      ADHD being treated with pharmacotherapy. Across 7 days, mothers and children (27
      ADHD; 25 non-ADHD) independently reported their moods, behaviors, and social
      contexts every 30 min during nonschool hours. Symptomatic behaviors and negative
      moods were elevated in the ADHD group, combined with maternal perceptions of
      lower parenting effectiveness and quality of life. Differences in the contexts of
      maternal anger were salient, with mothers in the ADHD group more often angry when
      with their children and comparison mothers more often angry when not. Although
      mothers' diaries were more informative, children's diaries also distinguished the
      two groups, especially during mornings and weekends. The need for family-wide
      interventions, the utility of child self-reports, and the promise of electronic
      diaries are discussed.

PMID- 16463074
TI  - Totally extraperitoneal (TEP) hernia repair after radical prostatectomy or
      previous lower abdominal surgery: is it safe? A prospective study.
AB  - BACKGROUND: Many practicing surgeons claim that hernias after previous lower
      abdominal surgery should be treated by transabdominal preperitoneal repair
      (TAPP). Moreover, previous radical prostatectomy contraindicates the laparoscopic
      approach for hernia repair. This prospective study was designed to examine the
      feasibility and to evaluate the surgical outcome of laparoscopic totally
      extraperitoneal (TEP) hernia repair in patients who had undergone previous lower
      abdominal surgery or radical prostatectomy, and to compare this group to all
      patients who underwent laparoscopic TEP without previous surgery during the study
      period. METHODS: Patients undergoing elective inguinal hernia repair, by one
      staff surgeon, in the Department of Abdominal Surgery at the Institute of
      Laparoscopic Surgery (ILS, Bordeaux) between September 2003 and December 2004
      were prospectively enrolled to this study. Three groups were defined--patients
      with previous radical prostatectomy, patients with previous lower abdominal
      surgery, and patients without previous surgery--and their data were analyzed and
      compared. RESULTS: A total of 256 laparoscopic inguinal hernia repairs were
      performed in 202 patients. Of these, 148 patients had unilateral hernia (143
      right and 113 left) and 54 patients had bilateral hernias. There were 166 male
      patients and 36 female patients with a mean age of 61 +/- 16 years. Of these, 10
      patients had inguinal hernia after prostatectomy and 15 patients had inguinal
      hernia after previous lower abdominal surgery. The mean operative time was
      significantly longer in the patients with previous prostatectomy than in the two
      other groups. Two patients after prostatectomy were converted to TAPP due to
      surgical difficulties. There were no major intraoperative complications in all
      patients except for three cases of bleeding arising from the inferior epigastric
      artery: two in the postprostatectomy group and one in a patient without previous
      surgery. Both ambulation and hospital stay were similar for all groups. Only one
      patient without previous surgery had postoperative bleeding and was reoperated on
      several hours after the hernia repair. During the follow-up period of 8 +/- 4
      months, there was no recurrence of the hernia in any group. CONCLUSIONS:
      Laparoscopic TEP for inguinal hernia repair in patients after previous low
      abdominal surgery has good results, similar to those in patients without previous
      surgery. Despite a longer operative time, TEP repairs can be performed
      efficiently and safely in patients after prostatectomy by skilled and experienced
      laparoscopic surgeons.

PMID- 16463075
TI  - [Pulmonary hypertension].
AB  - Pulmonary hypertension can arise in the presence of acute cardiopulmonary
      decompensation or develop as a chronic and progressive disease in association
      with connective tissue diseases, infectious diseases, or metabolic diseases, or
      in the form of idiopathic pulmonary hypertension. Impaired regulation of
      endogenous vasoactive mediators, growth factors, and thrombotic factors leads to
      pulmonary artery vasoconstriction, endothelial and epithelial proliferation, and
      thrombotic vascular obstruction, with resulting right heart failure. There is no
      curative treatment for chronic pulmonary hypertension, and the immediate
      objective of palliative treatment is to relieve right heart stress by reducing
      pulmonary arterial pressure with the aid of pulmonary vasodilators. Depending on
      the severity of the illness, perioperative mortality is high, which must be borne
      in mind by both anesthetists and intensivists. Chronic medical treatment for
      these patients must be optimized before any surgery is undertaken. In the
      perioperative period, it is essential that anything that could lead to worsening
      of pulmonary hypertension is avoided, or at least recognized and treated at an
      early stage. Intraoperatively, imminent acute right heart decompensation is
      treated by improving right-ventricular contractility and reducing right
      ventricular afterload. In the postoperative period, monitoring and optimization
      of the cardiopulmonary status, adequate analgesia and sedation, and careful
      anticoagulation must be ensured.

PMID- 16463076
TI  - [Operative management in axillary brachial plexus blocks: comparison of
      ultrasound and nerve stimulation].
AB  - Given a case-by-case accounting system, the analysis of medical performance
      becomes increasingly important. Quality of treatment and the time effort attached
      play an important role. Anaesthesia procedures require a high level of quality
      and safety. Moreover, they are personnel intensive. In the area of regional
      anaesthesia, new procedures such as the use of high definition ultrasonography
      for nerve blocks, allow a possible time gain as well as improved quality. The aim
      of this investigation was to analyze the impact on time and results when using
      ultrasonography or nerve stimulation for axillary brachial plexus blocks.
      Therefore, over a time period of 9 months, the ultrasound-guided plexus
      anaesthesia (Sono) and the neurostimulation methods (NStim) were investigated
      based upon the anaesthesia documentation of patients undergoing hand surgery.
      Only those cases were included where an axillary brachial plexus block had been
      performed, incomplete protocols were excluded and 1.5% mepivacaine was used as
      medication. Overall, a total of 130 cases fulfilled these criteria. The success
      rates, time consumption and timelines were evaluated. All data was stored on an
      Excel-sheet and statistically evaluated. The results revealed a significant
      increase in the success rate for the patient group where ultrasound was used
      (98.2% Sono vs 83.1% NStim) and the operation could begin 15 min earlier in the
      Sono group (5 min vs. 20 min, p<0.001). Furthermore, the duration of anaesthesia
      was significantly shorter (85 min vs. 120 min, p<0.001) and the necessity for
      post-operative observation was less (5.4% vs. 32.4%, p<0.001). The data provided
      in the study indicate that the use of ultrasound for the identification of the
      nerves can clearly improve quality and time-scales of axillary brachial plexus
      blocks.

PMID- 16463077
TI  - Purification, characterization, and molecular cloning of organic-solvent-tolerant
      cholesterol esterase from cyclohexane-tolerant Burkholderia cepacia strain ST
      200.
AB  - Extracellular cholesterol esterase of Burkholderia cepacia strain ST-200 was
      purified from the culture supernatant. Its molecular mass was 37 kDa. The enzyme
      was stable at pH 5.5-12 and active at pH 5.5-6, showing optimal activity at pH
      7.0 at 45 degrees C. Relative to the commercially available cholesterol
      esterases, the purified enzyme was highly stable in the presence of various water
      miscible organic solvents. The enzyme preferentially hydrolyzed long-chain fatty
      acid esters of cholesterol, except for that of cholesteryl palmitate. The enzyme
      exhibited lipolytic activity toward various p-nitrophenyl esters. The hydrolysis
      rate of p-nitrophenyl caprylate was enhanced 3.5- to 7.2-fold in the presence of
      5-20% (vol/vol) water-miscible organic solvents relative to that in the absence
      of organic solvents. The structural gene encoding the cholesterol esterase was
      cloned and sequenced. The primary translation product was predicted to be 365
      amino acid residues. The mature product is composed of 325 amino acid residues.
      The amino acid sequence of the product showed the highest similarity to the
      lipase LipA (87%) from B. cepacia DSM3959.

PMID- 16463078
TI  - Influence of temperature on the production of an archaeal thermoactive alcohol
      dehydrogenase from Pyrococcus furiosus with recombinant Escherichia coli.
AB  - The heterologous production of a thermoactive alcohol dehydrogenase (AdhC) from
      Pyrococcus furiosus in Escherichia coli was investigated. E. coli was grown in a
      fed-batch bioreactor in minimal medium to high cell densities (cell dry weight 76
      g/l, OD600 of 150). Different cultivation strategies were applied to optimize the
      production of active AdhC, such as lowering the cultivation temperature from 37
      to 28 degrees C, heat shock of the culture from 37 to 42 degrees C and from 37 to
      45 degrees C, and variation of time of induction (induction at an OD600 of 40, 80
      and 120). In addition to the production of active intracellular protein,
      inclusion bodies were always observed. The maximal activity of 30 U/l
      (corresponding to 6 mg/l active protein) was obtained after a heat shock from 37
      to 42 degrees C, and IPTG induction of the adhC expression at an OD600 of 120.
      Although no general rules can be provided, some of the here presented variations
      may be applicable for the optimization of the heterologous production of proteins
      in general, and of thermozymes in particular.

PMID- 16463079
TI  - Anatomical and surgical considerations of the sacrotuberous ligament and its
      relevance in pudendal nerve entrapment syndrome.
AB  - In view of the paucity of literature, this study was undertaken to reappraise the
      gross anatomy of the sacrotuberous ligament (STL), with the objective of
      providing an accurate anatomical basis for clinical conditions involving the STL.
      We studied the gross anatomy of the STL in 50 formalin fixed cadavers (100 sides)
      during the period of 2004-2005. All specimens exhibited an STL with a ligamentous
      part and (87%) of specimens exhibited a membranous (falciform) segment, which
      extended towards the ischioanal fossa. The variations of the falciform extensions
      were classified into three types. In Type I (69%), the falciform process extended
      towards and along the ischial ramus to terminate at the obturator fascia. In Type
      II (108%), the falciform process extended along the ischial ramus, fused with the
      obturator fascia and continued towards the ischioanal fossa. In addition, the
      medial border of the falciform process descended to fuse with the anococcygeal
      ligament, forming a continuous membrane. Lastly, in Type III (13%), the falciform
      process of the STL was absent. The above mentioned data could have an important
      implication to the understanding of the relationship between the pudendal nerve
      and the sacrotuberous ligament and their relevance to pudendal nerve entrapment
      syndrome.

PMID- 16463080
TI  - Variability of the pulmonary oblique fissures presented by high-resolution
      computed tomography.
AB  - The purpose of the study was to evaluate the radiological anatomy of oblique
      fissures (OFs) on high-resolution computed tomography (HRCT) scans. We
      retrospectively reviewed HRCT scans of 144 patients with normal lung parenchyma.
      The uppermost level of OFs with respect to the ribs, configuration (concave,
      straight, convex and others), orientation (medial or lateral facing), rotation
      and completeness of OFs were recorded. The most cranial level of the left OF was
      seen between the third and sixth ribs, and all but one were seen above or at the
      same level as the right OF. The uppermost extent of the OF was between the third
      and fourth intercostal space and seventh rib on the right lung. Only 2.2% of the
      right and 1.6% of the left OFs followed a parallel course to the ribs. The
      configuration of the OFs was generally concave in the upper zones (85.8% on the
      right and 72.1% on the left) and convex in the middle and lower lung zones (79.3%
      on the right and 73.9% on the left); 62.5% of the right and 59.7% of the left OFs
      were incomplete. Suprahilar portions of both OFs (98.9% on the right and 96.7% on
      the left) and the infrahilar portion of the right OF (54.2%) were generally
      facing laterally, whereas the infrahilar portion of the left OF was facing
      medially (80.9%). Angles of the MFs differed at the upper and lower levels. We
      detected reversal of 21 OFs in their craniocaudal course. In conclusion, the
      radiological anatomy of the right OF differs from the left OF. The uppermost
      extent of the left OF is almost always higher than the right. Thus, higher
      position of the right OF compared with the left almost always indicates a
      pathological process. Assessment of the angles of the OFs or comparison of the
      two sides cannot be used for the diagnosis of parenchymal disease like
      atelectasis. Occasionally, the classical propeller-like configuration is
      disrupted by the reverse course of the caudal part of the OF.

PMID- 16463081
TI  - Anatomical evaluation and clinical importance of the tibiofibular syndesmosis
      ligaments.
AB  - The aim of this study was to describe the detailed anatomical arrangement of
      ligaments of the tibiofibular syndesmosis and to highlight the clinical aspects
      of fracture dislocations. This study was performed on 42 legs of adult human
      embalmed cadavers. Tibiofibular syndesmosis ligaments attachments and their
      mutual relationships were described and their dimensions were measured. The
      anterior tibiofibular ligament is usually composed of three parts. This ligament
      runs obliquely at laterodistaly direction making 35 degrees angle with horizontal
      plane and posteriorly 65 degrees angle with sagittal plane. The posterior
      tibiofibular ligament runs almost horizontally 20 degrees angle with horizontal
      plane. The mean thicknesses of tibial and fibular attachments are 6.38+/-1.91 mm
      and 9.67+/-1.74 mm, respectively. The inferior transverse ligament originates
      from just below the posterior tibiofibular ligament, which has variations on the
      shape and dimensions due to its attachment points. The average length is 36.60+/
      9.51 mm. The network between the fibular notch and the distal fibula has been
      filled with the interosseous tibiofibular ligament whose fibers follow the
      laterodistal and anterior direction from the tibia to the fibula. It lies
      proximally 30-40 mm from the mortise. At the inferior view of the tibiofibular
      syndesmosis a pyramidal shaped cartilaginous facet was observed which was
      attached to the fibula. The length of this cartilage was variable. Some of
      synovial plicas from the ankle joints synovial membrane were observed at this
      view. We conclude that the results of this study may be useful to both orthopedic
      surgeons and radiologists for anatomic evaluation of the tibiofibular syndesmosis
      area.

PMID- 16463083
TI  - Design and control optimization of microclimate liquid cooling systems underneath
      protective clothing.
AB  - The use of protective clothing, whether in space suits, hazardous waste disposal,
      or sporting equipment, generally increases the risk of heat stress and
      hyperthermia by impairing the capacity for evaporative heat exchange from the
      body to the environment. To date the most efficient method of microclimate
      cooling underneath protective clothing has been via conductive heat exchange from
      circulating cooling fluid next to the skin. In order to make the use of liquid
      microclimate cooling systems ((LQ)MCSs) as portable and practical as possible,
      the physiological and biomedical engineering design goals should be towards
      maximizing the efficiency of cooling to maintain thermal comfort/neutrality with
      the least cooling possible to minimize coolant and power requirements. Meeting
      these conditions is an extremely complex task that requires designing for a
      plethora of different factors. The optimal fitting of the (LQ)MCSs, along with
      placement and design of tubing and control of cooling, appear to be key avenues
      towards maximizing efficiency of heat exchange. We review the history and major
      design constraints of (LQ)MCSs, the basic principles of human thermoregulation
      underneath protective clothing, and explore potential areas of research into
      tubing/fabric technology, coolant distribution, and control optimization that may
      enhance the efficiency of (LQ)MCSs.

PMID- 16463084
TI  - Development of ligament-like structural organization and properties in cell
      seeded collagen scaffolds in vitro.
AB  - Acute anterior cruciate ligament (ACL) injuries lead to poor joint function,
      instability, and eventually osteoarthritis if left untreated. Current surgical
      treatment options are not ideal; however, tissue engineering may provide
      mechanically sound, biocompatible reconstructions. Collagen fiber scaffolds were
      combined with fibroblast-seeded collagen gels and maintained in culture for up to
      20 days. The tensile and viscoelastic behavior of the constructs closely mimicked
      that of natural ligament. Constructs' mechanical and viscoelastic properties did
      not degrade over time in culture, and peak stress was significantly higher for
      constructs with embedded fibroblasts. Immunocytochemical and histological
      analyses demonstrated cell proliferation and ligament-like organization. We have
      created an engineered tissue that closely approaches key mechanical and
      viscoelastic properties of the ACL, does not degrade after 20 days in culture,
      and is histologically similar to the native tissue. This study should aid in
      developing effective treatments for ACL injury.

PMID- 16463085
TI  - On prediction of epileptic seizures by means of genetic programming artificial
      features.
AB  - A general-purpose, systematic algorithm is presented, consisting of a genetic
      programming module and a k-nearest neighbor classifier to automatically create
      artificial features--computer-crafted features possibly without a known physical
      meaning--directly from the reconstructed state-space trajectory of intracranial
      EEG signals that reveal predictive patterns of epileptic seizures. The algorithm
      was evaluated with IEEG data from seven patients, with prediction defined over a
      horizon of 1-5 min before unequivocal electrographic onset. A total of 59
      baseline epochs (nonseizures) and 55 preictal epochs (preseizures) were used for
      validation purposes. Among the results, it is shown that 12 seizures out of 55
      were missed while four baseline epochs were misclassified, yielding 79%
      sensitivity and 93% specificity.

PMID- 16463086
TI  - A high resolution approach to estimating time-frequency spectra and their
      amplitudes.
AB  - A high resolution approach to estimating time-frequency spectra (TFS) and
      associated amplitudes via the use of variable frequency complex demodulation
      (VFCDM) is presented. This is a two-step procedure in which the previously
      developed time-varying optimal parameter search (TVOPS) technique is used to
      obtain TFS, followed by using the VFCDM to obtain even greater TFS resolution and
      instantaneous amplitudes associated with only the specific frequencies of
      interest. This combinational use of the TVOPS and the VFCDM is termed the TVOPS
      VFCDM. Simulation examples are provided to demonstrate the performance of the
      TVOPS-VFCDM for high resolution TFS as well as instantaneous amplitude
      estimation. The simulation results show that the TVOPS-VFCDM approach provides
      the highest resolution and most accurate amplitude estimates when compared to the
      smoothed pseudo Wigner-Ville, continuous wavelet transform and Hilbert-Huang
      transform methods. Application of the TVOPS-VFCDM to renal blood flow data
      indicates some promise of a quantitative approach to understanding the dynamics
      of renal autoregulatory mechanisms as well as a possible approach to
      quantitatively discriminating between different strains of rats.

PMID- 16463087
TI  - Nanostructured probes for RNA detection in living cells.
AB  - The ability to visualize in real-time the expression level and localization of
      specific RNAs in living cells can offer tremendous opportunities for biological
      and disease studies. Here we review the recent development of nanostructured
      oligonucleotide probes for living cell RNA detection, and discuss the biological
      and engineering issues and challenges of quantifying gene expression in vivo. In
      particular, we describe methods that use dual FRET (fluorescence resonance energy
      transfer) or single molecular beacons in combination with peptide-based or
      membrane-permeabilization-based delivery, to image the relative level,
      localization, and dynamics of RNA in live cells. Examples of detecting endogenous
      mRNAs, as well as imaging their subcellular localization and colocalization are
      given to illustrate the biological applications, and issues in molecular beacon
      design, probe delivery, and target accessibility are discussed. The
      nanostructured probes promise to open new and exciting opportunities in sensitive
      gene detection for a wide range of biological and medical applications.

PMID- 16463088
TI  - Molecular analysis of malassezia microflora from patients with pityriasis
      versicolor.
AB  - BACKGROUND: Pityriasis versicolor (PV) is a superficial infection of the stratum
      corneum caused by Malassezia species. Eleven species have been identified within
      this genus, namely M. globosa, M. restricta, M. sympodialis, M. furfur, M.
      obtusa, M. slooffiae, M. pachydermatis, M. dermatis, M. japonica, M. yamatoensis,
      M. nana. M. furfur has long been identified as the causative fungus of PV.
      However, recent studies using the culture and isolation identified by
      morphological and physiological characteristics suggest that M. globosa is the
      causative agent of PV. OBJECTIVES: The aim of this study was to examine the
      distribution of PV microorganisms with a molecular-based non-culture method.
      PATIENTS: The subjects were 49 patients with PV (32 males, 17 females; 16-83
      years old) who visited our outpatient clinic. METHODS: Samples were taken from
      lesions for direct microscopy with methylene blue and detected Malassezia species
      without M. pachydermatis and M. nana using a non-culture-based method consisting
      of nested PCR with specific primers. RESULTS: The most frequently isolated
      species were M. globosa and M. restricta (both 93.9%). Only M. globosa was
      detected from the lesion in which the mycelial form alone was observed
      microscopically, but M. restricta was not. CONCLUSIONS: Our results suggest that
      M. globosa is the causative agent of PV.

PMID- 16463089
TI  - An archived lot of coccidioidin induces specific coccidioidal delayed-type
      hypersensitivity and correlates with in vitro assays of coccidioidal cellular
      immune response.
AB  - No test for assessing cellular immune response in coccidioidomycosis is currently
      available in the United States. In the present study, we tested 49 healthy
      subjects living in the coccidioidal endemic region with a 1:55.8 dilution of a
      single lot of coccidioidin archived since the 1970s. In this group, 23 evaluable
      subjects demonstrated >/=5 mm of induration at 24, 48 or 72 h, with a mean+/-SEM
      maximum induration of 18.4+/-4.0 mm. The induration results among 14 subjects
      reactive at 24 h were compared to those from 179 individuals in an historical
      cohort studied in the 1980s using a reference lot of coccidioidin. Results were
      within 5% and not significantly different (P=0.924). The maximum induration
      response of all evaluable subjects correlated significantly with the results of
      in vitro tests of coccidioidal cellular immunity using supernatant interferon
      gamma concentration and CD69 expression on T cells (Spearman rank correlation
      coefficients 0.69 and 0.68, respectively; P<0.01 for both). These data suggest
      that archived coccidioidin retains its potency and specificity and that in vitro
      test of coccidioidal immunity may have utility in the measurement of coccidioidal
      cellular immunity.

PMID- 16463090
TI  - Clinical evolution of paracoccidioidomycosis in 38 children and teenagers.
AB  - Paracoccidioidomycosis (PCM) in children is rare, and its clinical progression is
      not clearly understood. The admission and post-admission clinical records of 38
      children and teenagers aged up to 14 were studied who had been under treatment
      for 24-30 months. It is a consecutive case series, 17 retrospective and 21
      prospective, from 1977 to 2000, admitted before and after 1990, respectively. The
      main clinical presentations were lymphatic, abdominal and cutaneous involvement,
      and fever. The alterations which disappeared more slowly were lymphadenomegaly,
      hepatomegaly, splenomegaly, and osteoarticular pain. Poor intestinal absorption,
      esophageal varices and splenic calcification were observed before treatment and
      persisted as sequelae. There was a satisfactory response to initial treatment in
      56.7% of cases. Half the patients became asymptomatic in the ninth month of
      treatment, and 17+/-8% of cases presented with at least one symptom of the
      disease after 30 months of treatment. There were five deaths, and treatment
      failure was frequent and associated in part with the irregular use of antifungal.
      Treatment with ketoconazole was safe and effective. PCM is a serious systemic
      disease with slow evolution and high lethality, requiring treatment maintenance
      for a minimum of 24 months with careful and prolonged follow-up. Studies are
      necessary to evaluate the efficacy of different antifungals and the ideal
      treatment length for children with PCM.

PMID- 16463092
TI  - Comparison of aflatoxigenic and nonaflatoxigenic isolates of Aspergillus flavus
      using DNA amplification fingerprinting techniques.
AB  - Aspergillus flavus is a filamentous fungus that produces mycotoxins in many food
      and feed crops, such as maize (Zea mays L.). Isolates were analyzed for toxin
      production by nucleic acid profiles in an attempt to differentiate aflatoxigenic
      from nonaflatoxigenic isolates. A total of 41 aflatoxigenic and 34
      nonalfatoxigenic isolates were included in the study. The isolates were evaluated
      initially using DNA amplification fingerprinting (DAF) without clear resolution
      of the groups. A weak association of aflatoxigenic isolates was observed, as
      evidenced by their clustering in 18 of 81 trees recovered from maximum parsimony
      analysis of binary characters derived from arbitrary signatures from
      amplification profiles (ASAP) data; nonaflatoxigenic isolates exhibited a pattern
      of paraphyletic laddering. Up to five markers unambiguously supported the
      aflatoxigenic isolate grouping, but the presence of alternative conflicting
      topologies in equally parsimonious trees precluded the observation of meaningful
      statistical support. With additional markers for genome of A. flavus, this method
      could be used to resolve toxigenic from nontoxigenic strains. This additional
      work could resolve aflatoxigenic isolates of A. flavus present on maize plants
      using ASAP, which would reduce labor intense costs and potentially lead to faster
      determination of resistant cultivars in breeding efforts.

PMID- 16463091
TI  - Cryptococcus neoformans and Cryptococcus gattii isolated from the excreta of
      psittaciformes in a southern Brazilian zoological garden.
AB  - Cryptococcus neoformans, a major pathogen in immunocompromised patients, is a
      ubiquitous free-living fungus that can be isolated from soils, avian excreta and
      plant material. To further study potential saprophytic sources of this yeast in
      the Southern Brazilian State Rio Grande do Sul, we analyzed fecal samples from 59
      species of captive birds kept in cages at a local Zoological Garden, belonging to
      12 different orders. Thirty-eight environmental isolates of C. neoformans were
      obtained only from Psittaciformes (Psittacidae, Cacatuidae and Psittacula). Their
      variety and serotype were determined, and the genetic structure of the isolates
      was analyzed by use of the simple repetitive microsatellite specific primer M13
      and the minisatellite specific primer (GACA)(4) as single primers in the PCR. The
      varieties were confirmed by pulsed-field gel electrophoresis (PFGE). Thirty-three
      isolates (87%) were from the var. grubii, serotype A, molecular type VNI and five
      (13%) were Cryptococcus gattii, serotype B, molecular type VGI. All the isolates
      were mating type alpha. Isolates were screened for some potential virulence
      factors. Quantitative urease production by the environmental isolates belonging
      to the C. gattii was similar to the values usually obtained for clinical ones.

PMID- 16463093
TI  - Host-specific variation in infection by toxigenic fungi and contamination by
      mycotoxins in pearl millet and corn.
AB  - Pearl millet is widely consumed in regions of Africa and Asia, and is
      increasingly being grown as an alternative grain in drought-prone regions of the
      United States. Pearl millet and corn were grown in dryland conditions at Tifton,
      Georgia, USA and grains were compared for pre-harvest infection by potentially
      toxigenic fungi and contamination by mycotoxins. Corn hybrids Agripro 9909 and
      Pioneer 3146, and pearl millet Tifgrain 102 were grown in 2000 and 2001; pearl
      millet HGM 100 was included in the test in 2001. Hybrids were sown on multiple
      planting dates in each year to induce variation in flowering time. Host species
      differed in the frequency of isolation of potentially toxigenic fungal species in
      both years. Across years, corn hybrids were more prone to infection by
      Aspergillus flavus Link (maximum isolation frequency = 8.8%) and Fusarium
      moniliforme Sheldon sensu lato (maximum isolation frequency = 72.8%), with
      corresponding greater concentrations of aflatoxins (maximum concentration = 204.9
      microg kg(-1)) and fumonisins (maximum concentration = 34,039 microg kg(-1)).
      Pearl millet was more prone to infection by F. semitectum Berk. & Ravenel
      (maximum isolation = 74.2%) and F. chlamydosporum Wollenweb & Reinking (maximum
      isolation = 33.0%), and contamination by moniliformin (maximum contamination =
      92.1 microg kg(-1)). Beauvericin (maximum concentration = 414.6 microg kg(-1))
      was present in both hosts. Planting date of corn affected aflatoxin and
      beauvericin contamination in 2000, and fumonisin concentration in 2001. The
      observed differences in mycotoxin contamination of the grains, which are likely
      due to host-specific differences in susceptibility to pre-harvest mycoflora, may
      affect food safety when the crops are grown under stress conditions.

PMID- 16463094
TI  - Characterization of an Indonesian isolate of Paecilomyces reniformis.
AB  - An entomopathogenic fungus (IndGH 96), identified as Paecilomyces reniformis, was
      isolated from long-horned grasshoppers (Orthoptera: Tettigoniidae) in Sulawesi,
      Indonesia. The phenotypic and molecular data identified the IndGH 96 as a P.
      reniformis. We present the first comprehensive characterization of this species
      using morphological features, sequencing of the ITS1-5.8s-ITS2 region, D1/D2
      region of 28S of rDNA, and a portion of the tubulin gene, and laboratory
      bioassays. Distinguishing features include a hyphal body stage during vegetative
      growth and the production of distinctly curved, light-green conidia. High dosage
      bioassays showed that IndGH 96 was infectious to both long-horned and short
      horned grasshoppers but not to the house cricket, Acheta domestica, or to the
      lepidopterans velvetbean caterpillar, Anticarsia gemmatalis or fall armyworm,
      Spodoptera frugiperda. Phenotypic and genetic analyses suggest that IndGH 96 and
      other isolates of P. reniformis are more closely related to Nomuraea rileyi than
      to other species of Paecilomyces.

PMID- 16463095
TI  - Antimicrobial activities of the essential oils of various plants against tomato
      late blight disease agent Phytophthora infestans.
AB  - The aim of this study was to find an alternative to synthetic fungicides
      currently used in the control of devastating oomycete pathogen Phytophthora
      infestans, causal agent of late blight disease of tomato. Antifungal activities
      of essential oils obtained from aerial parts of aromatic plants such as oregano
      (Origanum syriacum var. bevanii), thyme (Thymbra spicata subsp. spicata),
      lavender (Lavandula stoechas subsp. stoechas), rosemary (Rosmarinus officinalis),
      fennel (Foeniculum vulgare), and laurel (Laurus nobilis), were investigated
      against P. infestans. Both contact and volatile phase effects of different
      concentrations of the essential oils used were determined by using two in vitro
      methods. Chemical compositions of the essential oils were also determined by GC
      MS analysis. Major compounds found in essential oils of thyme, oregano, rosemary,
      lavender, fennel and laurel were carvacrol (37.9%), carvacrol (79.8), borneol
      (20.4%), camphor (20.2%), anethole (82.8%) and 1,8-cineole (35.5%), respectively.
      All essential oils were found to inhibit the growth of P. infestans in a dose
      dependent manner. Volatile phase effect of oregano and thyme oils at 0.3
      microg/ml air was found to completely inhibit the growth of P. infestans.
      Complete growth inhibition of pathogen by essential oil of fennel, rosemary,
      lavender and laurel was, however, observed at 0.4-2.0 microg/ml air
      concentrations. For the determination of the contact phase effects of the tested
      essential oils, oregano, thyme and fennel oils at 6.4 microg/ml were found to
      inhibit the growth of P. infestans completely. Essential oils of rosemary,
      lavender and laurel were inhibitory at relatively higher concentrations (12.8,
      25.6, 51.2 microg/ml respectively). Volatile phase effects of essential oils were
      consistently found to be more effective on fungal growth than contact phase
      effect. Sporangial production was also inhibited by the essential oil tested.
      Light and scanning electron microscopic (SEM) observation on pathogen hyphae,
      exposed to both volatile and contact phase of oil, revealed considerable
      morphological alterations in hyphae such as cytoplasmic coagulation,
      vacuolations, hyphal shrivelling and protoplast leakage.

PMID- 16463096
TI  - A map of KNAT gene expression in the Arabidopsis root.
AB  - Homeodomain proteins are key regulators of patterning during the development of
      animal and plant body plans. Knotted1-like TALE homeodomain proteins have been
      found to play important roles in the development of the Arabidopsis shoot apical
      meristem and are part of a complex regulatory network of protein interactions. We
      have investigated the possible role of the knotted1-like genes KNAT1, KNAT3,
      KNAT4, and KNAT5 in Arabidopsis root development. Root growth is indeterminate,
      and the organ shows distinct zones of cell proliferation, elongation and
      differentiation along its longitudinal axis. Here we show that KNAT1, KNAT3,
      KNAT4 and KNAT5 show cell type specific expression patterns in the Arabidopsis
      root. Moreover, they are expressed in different spatially restricted patterns
      along the longitudinal root axis and in lateral root primordia. Hormones play an
      important role in maintenance of root growth, and we have studied their effect on
      KNAT gene expression. We show that KNAT3 expression is repressed by moderate
      levels of cytokinin. In addition, we show that the subcellular localization of
      KNAT3 and KNAT4 is regulated, indicating post-translational control of the
      activities of these transcription factors. The regulated expression of KNAT1,
      KNAT3, KNAT4 and KNAT5 within the Arabidopsis root suggests a role for these
      genes in root development. Our data provide the first systematic survey of KNAT
      gene expression in the Arabidopsis root.

PMID- 16463097
TI  - Dirigent proteins in conifer defense: gene discovery, phylogeny, and differential
      wound- and insect-induced expression of a family of DIR and DIR-like genes in
      spruce (Picea spp.).
AB  - The outer stem tissues of conifers provide a durable constitutive and inducible
      defense barrier consisting of suberized or lignified periderm, sclereids, a
      network of terpenoid-filled resin ducts, and phenolic phloem parenchyma cells.
      Microarray gene expression profiling of Sitka spruce (Picea sitchensis) bark
      attacked by stem-boring weevils (Pissodes strobi) or through mechanical wounding
      demonstrated significant accumulation of transcripts resembling dirigent protein
      (DIR) genes. To investigate this gene family and its spatial and temporal
      patterns of expression in conifer defense, we isolated cDNAs representing 19
      unique DIR and DIR-like genes from Sitka spruce, white spruce (P. glauca), and
      interior spruce (P. glauca x engelmannii). Sequence alignments also identified a
      large number of DIR-like proteins in other plant species, which share several
      conserved protein motifs with known DIR proteins. Phylogenetic analysis of 72 DIR
      and DIR-like proteins suggests five distinct subfamilies, DIR-a and four DIR-like
      subfamilies (DIR-b, DIR-c, DIR-d and DIR-e). Previously characterized members of
      the DIR-a subfamily direct stereoselective phenolic coupling reactions in the
      formation of lignans and possibly lignins. The spruce genes identified here are
      members of the DIR-a and DIR-b subfamilies. Using gene-specific quantitative real
      time PCR we measured constitutive expression for six DIR-a genes and three DIR
      like genes in different stem tissues, green shoot tips, and roots of Sitka
      spruce. DIR-like genes revealed ubiquitous high expression in all tissues. In
      contrast, the six DIR-a genes showed a gradient of transcript abundance in stem
      tissues with highest levels in the outer cortex and lowest levels in the inner
      xylem. Gene-specific transcript profiling of six DIR-a genes confirmed rapid and
      strong accumulation (up to 500-fold) in wound- and weevil-induced stem bark and
      xylem. These findings suggest a role for spruce DIR genes in constitutive and
      induced phenolic defense mechanisms against stem-boring insects.

PMID- 16463098
TI  - Molecular cloning and characterization of a vacuolar H+ -pyrophosphatase gene,
      SsVP, from the halophyte Suaeda salsa and its overexpression increases salt and
      drought tolerance of Arabidopsis.
AB  - The chenopodiaceae Suaeda salsa L. is a leaf succulent euhalophyte. Shoots of the
      S. salsa are larger and more succulent when grown in highly saline environments.
      This increased growth and water uptake has been correlated with a large and
      specific cellular accumulation of sodium. S. salsa does not have salt glands or
      salt bladders on its leaves. Thus, this plant must compartmentalize the toxic
      Na(+) in the vacuoles. The ability to compartmentalize sodium may result from a
      stimulation of the proton pumps that provide the driving force for increased
      sodium transport into the vacuole. In this work, we isolated the cDNA of the
      vacuolar membrane proton-translocating inorganic pyrophosphatase (H(+) -PPase)
      from S. salsa. The SsVP cDNA contains an uninterrupted open reading frame of 2292
      bp, coding for a polypeptide of 764 amino acids. Northern blotting analysis
      showed that SsVP was induced in salinity treated leaves. The activities of both
      the V-ATPase and the V-PPase in Arabidopsis overexpressing SsVP-2 is higher
      markedly than in wild-type plant under 200 mM NaCl and drought stresses. The
      Overexpression of SsVP can increase salt and drought tolerance of transgenic
      Arabidopsis.

PMID- 16463099
TI  - Transcriptional regulation of ABI3- and ABA-responsive genes including RD29B and
      RD29A in seeds, germinating embryos, and seedlings of Arabidopsis.
AB  - ABA-responsive elements (ABREs) are cis-acting elements and basic leucine zipper
      (bZIP)-type ABRE-binding proteins (AREBs) are transcriptional activators that
      function in the expression of RD29B in vegetative tissue of Arabidopsis in
      response to abscisic acid (ABA) treatment. Dehydration-responsive elements (DREs)
      function as coupling elements of ABRE in the expression of RD29A in response to
      ABA. Expression analysis using abi3 and abi5 mutants showed that ABI3 and ABI5
      play important roles in the expression of RD29B in seeds. Base-substitution
      analysis showed that two ABREs function strongly and one ABRE coupled with DRE
      functions weakly in the expression of RD29A in embryos. In a transient
      transactivation experiment, ABI3, ABI5 and AREB1 activated transcription of a GUS
      reporter gene driven by the RD29B promoter strongly but these proteins activated
      the transcription driven by the RD29A promoter weakly. In 35S::ABI3 Arabidopsis
      plants, the expression of RD29B was up-regulated strongly, but that of RD29A was
      up-regulated weakly. These results indicate that the expression of RD29B having
      ABREs in the promoter is up-regulated strongly by ABI3, whereas that of RD29A
      having one ABRE coupled with DREs in the promoter is up-regulated weakly by ABI3.
      We compared the expression of 7000 Arabidopsis genes in response to ABA treatment
      during germination and in the vegetative growth stage, and that in 35S::ABI3
      plants using a full-length cDNA microarray. The expression of ABI3- and/or ABA
      responsive genes and cis-elements in the promoters are discussed.

PMID- 16463101
TI  - Fine mapping and in silico isolation of the EUI1 gene controlling upper internode
      elongation in rice.
AB  - Upper internode elongation in rice is an important agronomic trait. Well-known
      mutants with an elongated uppermost internode (eui) are important germplasms for
      developing unsheathed-panicle male-sterile lines in hybrid rice breeding. We
      finely mapped the eui1 gene and identified its candidate gene using in silico
      analysis based on previous research work and rice genomic sequence data. The rice
      eui1 gene was mapped to two overlapping BAC clones, OSJNBa0095J22 and
      OSJNBb0099O15, between the markers AC40 and AC46, that were 0.64 cM apart and
      spanned approximately 152 kb. A simple sequence repeat (SSR) marker AC41 that
      cosegregated with eui1 was located in an intron of a putative cytochrome P450
      related gene. In silico analysis suggested that this encoded the cytochrome
      CYP714D1. Allelic sequencing confirmed that EUI1 corresponded to this P450 gene.
      A gamma ray-induced eui1 mutant carried a deletion in exon II of the EUI1 gene,
      and resulted in a frame-shift deletion that produced a truncated polypeptide. We
      conclude that the EUI1 gene controlling the upper internode elongation in rice is
      9,804 bp long, and comprises two exons and one intron. The length of the cDNA is
      1,931 bp containing a 1,734 bp ORF, a 110 bp 5'-UTR and a 87 bp 3'-UTR. The ORF
      encodes an unknown 577 amino acid functional protein, that appears to be a member
      of the cytochrome P450 family.

PMID- 16463100
TI  - Features of Arabidopsis genes and genome discovered using full-length cDNAs.
AB  - Arabidopsis is currently the reference genome for higher plants. A new, more
      detailed statistical analysis of Arabidopsis gene structure is presented
      including intron and exon lengths, intergenic distances, features of promoters,
      and variant 5'-ends of mRNAs transcribed from the same transcription unit. We
      also provide a statistical characterization of Arabidopsis transcripts in terms
      of their size, UTR lengths, 3'-end cleavage sites, splicing variants, and coding
      potential. These analyses were facilitated by scrutiny of our collection of
      sequenced full-length cDNAs and much larger collection of 5'-ESTs, together with
      another set of full-length cDNAs from Salk/Stanford/Plant Gene Expression
      Center/RIKEN. Examples of alternative splicing are observed for transcripts from
      7% of the genes and many of these genes display multiple spliced isoforms. Most
      splicing variants lie in non-coding regions of the transcripts. Non-canonical
      splice sites constitute less than 1% of all splice sites. Genes with fewer than
      four introns display reduced average mRNA levels. Putative alternative
      transcription start sites were observed in 30% of highly expressed genes and in
      more than 50% of the genes with low expression. Transcription start sites
      correlate remarkably well with a CG skew peak in the DNA sequences. The
      intergenic distances vary considerably, those where genes are transcribed towards
      one another being significantly shorter. New transcripts, missing in the current
      TIGR genome annotation and ESTs that are non-coding, including those antisense to
      known genes, are derived and cataloged in the Supplementary Material. They
      identify 148 new loci in the Arabidopsis genome. The conclusions drawn provide a
      better understanding of the Arabidopsis genome and how the gene transcripts are
      processed. The results also allow better predictions to be made for, as yet,
      poorly defined genes and provide a reference for comparisons with other plant
      genomes whose complete sequences are currently being determined. Some comparisons
      with rice are included in this paper.

PMID- 16463102
TI  - The maize Oil yellow1 (Oy1) gene encodes the I subunit of magnesium chelatase.
AB  - Semi-dominant Oil yellow1 (Oy1) mutants of maize (Zea mays) are deficient in the
      conversion of protoporphyrin IX to magnesium protoporphyrin IX, the first
      committed step of chlorophyll biosynthesis. Using a candidate gene approach, a
      cDNA clone was isolated that was predicted to encode the I subunit of magnesium
      chelatase (ZmCHLI) and mapped to the same genetic interval as Oy1. Allelic
      variation was identified at ZmCHLI between wild-type plants and plants carrying
      semi-dominant alleles of Oy1. These differences revealed putative amino acid
      substitutions that could account for the alterations in protein function.
      Candidate lesions were tested by introduction of homologous changes into the
      Synechocystis magnesium chelatase I gene (SschlI) and characterization of the
      activity of mutant protein variants in an in vitro enzyme activity assay. The
      results of these analyses suggest that SsChlI protein variants containing the
      substitutions identified in the dominant Oy1 maize alleles lack activity
      necessary for magnesium chelation and confer a semi-dominant phenotype via
      competitive inhibition of wild-type SsChlI.

PMID- 16463103
TI  - The MYB transcription factor superfamily of Arabidopsis: expression analysis and
      phylogenetic comparison with the rice MYB family.
AB  - MYB proteins are a superfamily of transcription factors that play regulatory
      roles in developmental processes and defense responses in plants. We identified
      198 genes in the MYB superfamily from an analysis of the complete Arabidopsis
      genome sequence, among them, 126 are R2R3-MYB, 5 are R1R2R3-MYB, 64 are MYB
      related, and 3 atypical MYB genes. Here we report the expression profiles of 163
      genes in the Arabidopsis MYB superfamily whose full-length open reading frames
      have been isolated. This analysis indicated that the expression for most of the
      Arabidopsis MYB genes were responsive to one or multiple types of hormone and
      stress treatments. A phylogenetic comparison of the members of this superfamily
      in Arabidopsis and rice suggested that the Arabidopsis MYB superfamily underwent
      a rapid expansion after its divergence from monocots but before its divergence
      from other dicots. It is likely that the MYB-related family was more ancient than
      the R2R3-MYB gene family, or had evolved more rapidly. Therefore, the MYB gene
      superfamily represents an excellent system for investigating the evolution of
      large and complex gene families in higher plants. Our comprehensive analysis of
      this largest transcription factor superfamily of Arabidopsis and rice may help
      elucidate the possible biological roles of the MYB genes in various aspects of
      flowering plants.

PMID- 16463104
TI  - Characterization of cDNAs encoding two distinct miraculin-like proteins and
      stress-related modulation of the corresponding mRNAs in Citrus jambhiri lush.
AB  - Two distinct full-length cDNAs from rough lemon that encoded miraculin-like
      proteins were isolated by random amplification of cDNA ends (RACEs), based on
      sequence information from subtractive PCR previously described, and designated as
      RlemMLP1 and RlemMLP2. The transcripts of both RlemMLP1 and RlemMLP2 were not
      detected in leaves, or stems but accumulated in fruits. Transcripts accumulated
      to higher levels in leaves after wounding, inoculation with conidia of Alternaria
      alternata, or treatment with methyl jasmonate vapors. Treatment with methyl
      salicylate antagonized the signaling pathway of wounding. Treatment with methyl
      salicylate at 2 h after wounding significantly reduced wounding-induced gene
      expression of both RlemMLP1 and RlemMLP2. Protein products of these genes were
      obtained by using a prokaryotic expression system, and had protease inhibitor
      activity. RlemMLP2, but not RlemMLP1, contained a thaumatin motif, and only
      RlemMLP2 showed anti-fungal activity against Alternaria citri. Cellular
      localization analysis with RlemMLP1 or RlemMLP2 fused to a green fluorescence
      protein gene following transient translation using a particle bombardment in
      onion cells indicated that both RlemMLP1 and RlemMLP2 were localized to the
      cytosol. These evidences revealed that rough lemon RlemMLPs are likely to have
      defensive function against pathogens at least when host cells are broken by their
      infections.

PMID- 16463105
TI  - OsGLU1, a putative membrane-bound endo-1,4-beta-D-glucanase from rice, affects
      plant internode elongation.
AB  - A dwarf mutant glu was identified from screening of T-DNA tagged rice population.
      Genetic analysis of the T1 generation of glu revealed that a segregation ratio of
      wild-type:dwarf phenotype was 3:1, suggesting that the mutated phenotype was
      controlled by a single recessive nuclear locus. The mutated gene OsGLU1,
      identified by Tail-PCR, encodes a putative membrane-bound endo-1,4-beta-D
      glucanase, which is highly conserved between mono- and dicotyledonous plants.
      Mutation of OsGLU1 resulted in a reduction in cell elongation, and a decrease in
      cellulose content but an increase in pectin content, suggesting that OsGLU1
      affects the internode elongation and cell wall components of rice plants.
      Transgenic glu mutants harboring the OsGLU1 gene complemented the mutation and
      displayed the wild-type phenotype. In addition, OsGLU1 RNAi plants showed similar
      phenotype as the glu mutant has. These results indicate that OsGLU1 plays
      important roles in plant cell growth. Gibberellins and brassinosteroids induced
      OsGLU1 expression. In rice genome, endo-1,4-beta-D-glucanases form a multiple
      gene family with 15 members, and each may have a distinct expression pattern in
      different organs. These results indicate that endo-1,4-beta-D-glucanases may play
      diverse roles in growth and developmental process of rice plants.

PMID- 16463106
TI  - Dose-dependency of life span prolongation of F344/DuCrj rats injected with (
      )deprenyl.
AB  - The effect of (-)deprenyl (D) on prolonging survival has previously been reported
      in different species of animals. In rats, three studies reported a positive
      effect, while one study reported a shortening of life spans. In the present
      study, we attempted to clarify past discrepancies in the results based on the
      speculation that there exists a certain effective dose range for this effect of
      the drug. F344/DuCrj rats of both sexes began to receive subcutaneous (s.c.)
      injections of D at the age of 18 months at a dose of 0.25 mg/kg/injection (inj.),
      3 times a week. Control animals were given a vehicle (a saline solution). Average
      life spans of animals (days) were significantly increased in both male (895 +/-
      109.7, n=30; 967.8 +/- 88.6, n=30, control vs. D treated, P<0.01, t-test) and
      female (924.7 +/- 132.2, n=38; 987.1 +/- 133.4, n=39, P<0.05) rats by 8.1% and
      6.7%, respectively. We have previously reported that a dose of 0.5mg/kg/inj.
      (s.c.) significantly increased the life span of male F344 rats, while a dose of
      1.0 mg/kg/inj. somewhat shortened the life span, although the difference was not
      statistically significant. The results of the present study coupled with our
      previous reports clearly indicate that a proper dose of D within a certain dose
      range can significantly increase the life span of animals of both sexes, but that
      a greater dose becomes less effective and may actually adversely affect the life
      span of rats. The presence of this effective dose range of D may explain
      discrepancies in the effect of D on life spans of animals previously reported.

PMID- 16463107
TI  - Effect of recombinant human growth hormone administration on body composition and
      vascular function and structure in old male Wistar rats.
AB  - The process of ageing affects negatively both cardiovascular system and body
      composition. On the other hand, the hormones of the somatotrophic axis, growth
      hormone (GH) and insulin-like growth factor-I (IGF-I), whose production is
      reduced by age, are involved in the regulation of the cardiovascular system. The
      aim of this study was to investigate the effect of GH on body composition,
      vascular function and structure in old male rats. Old (20 months) and adult (4
      months) male Wistar rats were used. One group of old animals was treated with GH
      for 4 weeks. Periepididimary fat weight, Specific Gravity Index (SGI), dose
      responses to Acetylcholine (ACh), Isoproterenol (Iso), Phenylephrine (Phe) and
      ACh in the presence of NG-nitro-L: -arginine metylester (L-NAME; ACh + L-NAME),
      as well as vascular morphology in aortic rings, were studied. Old rats showed
      increased fat weight and decreased SGI as compared to adult animals. GH increased
      SGI and tended to reduce fat weight. Old rats showed an impairment in the
      vasodilator response to ACh and Iso; GH significantly improved the vasodilatation
      induced by Iso, whereas the response to ACh was not significantly enhanced by GH
      treatment. There were no significant differences between adult and old rats in
      the contractile response to Phe, and GH did not show any effect. Contraction
      induced by ACh + L-NAME was higher in old rats as compared to adults, and
      treatment with GH significantly reduced this response. Aortic media area was
      increased in old rats, and GH administration reduced this parameter. In
      conclusion, GH shows beneficial effects on body composition, as well as on
      vascular function and morphology in old male rats.

PMID- 16463108
TI  - Effect of S-adenosylmethionine on age-induced hepatocyte damage in old Wistar
      rats.
AB  - Aging is accompanied by changes in the morphology and physiology of organs and
      tissues, such as the liver. This process might be due to the accumulation of
      oxidative damage induced by reactive oxygen (ROS) and reactive nitrogen species
      (RNS). Hepatocytes are very rich in mitochondria and have a high respiratory
      rate, so they are exposed to large amounts of ROS and permanent oxidative stress.
      S-Adenosylmethionine (SAMe) is an endogenous metabolite that has shown to exert
      protective effects on different experimental pathological models in which free
      radicals are involved. The aim of this study was to investigate the effect of
      SAMe on age-induced damage in hepatocytes. For this purpose, male and female
      Wistar rats of 18 and 2 months of age were used. Cells were isolated and, after
      incubation in the presence or in the absence of SAMe, different parameters were
      measured. Aging induced a significant increase in nitric oxide, carbon monoxide
      and cGMP, and a reduction in reduced glutathione, ATP and phosphatidylcholine
      synthesis, as well as in methionine- adenosyl-transferase and methyl-transferase
      activities. Incubation of old cells with SAMe prevented all these age-related
      changes, reaching values in some of the parameters similar to those found in
      young animals. In conclusion, SAMe seems to have beneficial effects against age
      induced damage in hepatocytes.

PMID- 16463109
TI  - Expression and activity patterns of nitric oxide synthases and antioxidant
      enzymes reveal a substantial heterogeneity between cardiac and vascular aging in
      the rat.
AB  - We investigated the effects of aging and ischemia-reperfusion (I/R) injury on the
      expression and activity of nitric oxide (*NO) synthases and superoxide dismutase
      (SOD) isoforms. To this end we perfused excised hearts from young (6 months old)
      and old (31-34 months old) rats according to the Langendorff technique. The
      isolated hearts were, after baseline perfusion for 30 min, either subjected to 20
      min of global no-flow ischemia followed by 40 min of reperfusion or were control
      perfused (60 min normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained
      unchanged with increasing age and remained unaltered by I/R. However, SOD
      activity decreased from 7.55 +/- 0.1 U/mg protein in young hearts to 5.94 +/-
      0.44 in old hearts (P<0.05). Furthermore, I/R led to a further decrease in enzyme
      activity (to 6.35 +/- 0.41 U/mg protein; P<0.05) in myocardium of young, but not
      in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine
      levels could be detected. Endothelial NOS (eNOS) expression and activity remained
      unchanged in aged left ventricles, irrespective of I/R injury. This was in steep
      contrast to peripheral (renal and femoral) arteries obtained from the same
      animals where a marked age-associated increase of eNOS protein expression could
      be demonstrated. Inducible NOS expression was undetectable either in the
      peripheral arteries or in the left ventricle, irrespective of age. In particular
      when associated with an acute pathology, which is furthermore limited to a
      certain time frame, changes in the aged myocardium with respect to enzymes
      crucially involved in maintaining the redox homeostasis, seem to be much less
      pronounced or even absent compared to the vascular aging process. This may point
      to heterogeneity in the molecular regulation of the cardiovascular aging process.

PMID- 16463110
TI  - The Fischer 344/NNiaHSd X Brown Norway/BiNia is a better model of sarcopenia than
      the Fischer 344/NNiaHSd: a comparative analysis of muscle mass and contractile
      properties in aging male rat models.
AB  - Sarcopenia, characterized by profound muscle atrophy and the loss of contractile
      function, contributes significantly to the development of frailty and functional
      impairment in older age. Although present in aging humans, rat models have failed
      to clearly demonstrate a similar degree of this age-associated loss of muscle
      mass and function. This investigation compared two models of rats raised
      specifically for aging studies, the Fischer 344/NNiaHSd (F344/N) and the Fischer
      344/NNiaHSd X Brown Norway/BiNia (F344/NXBN), and sought to determine which model
      provides the most accurate representation of human sarcopenia. We found that
      aging had no effect on F344/N muscle mass or contractile function in the extensor
      digitorum longus (EDL) and soleus (SOL). Conversely, in the F344/NXBN model,
      aging was found to decrease EDL and SOL mass and contractile function. These
      changes were sufficient to satisfy the proposed criteria for the diagnosis of
      human sarcopenia based upon muscle mass and contractile function. Results
      indicate that the F344/NXBN provides a better model of the alterations seen in
      aging human muscle than the F344/N rat model.

PMID- 16463111
TI  - Effect of hormone replacement therapy in normalizing age related neuronal markers
      in different age groups of naturally menopausal rats.
AB  - Aging of the normal brain is accompanied by changes in its structure, function,
      and metabolism. There are significant gender differences in aging brain. Most of
      these changes increase during menopausal condition in females when the level of
      estradiol and progesterone are decreased. The objective of this study was to
      determine the effect of estradiol and progesterone (separate as well as combined)
      hormones in neuronal tissues from naturally menopausal rats of different age
      groups. Results show decreased activity of Acetylcholine esterase (AChE) whereas
      the level of lipid peroxidation increased with age, and after the hormone
      treatments both AChE activity and level of lipid peroxidation returned to control
      values. The deposition of lipofuscin, a pigment that accumulated intraneuronally
      in brain and other tissues and is considered a marker of aging, was increased
      with aging and the hormone treatment decreased this deposition. The present study
      clearly shows reduction in risk factors associated with aging in the murine model
      system by hormone treatments, namely estrogen and progesterone by increasing the
      activity of acetylcholine esterase and decreasing the levels of lipid
      peroxidation and lipofuscin deposition in different parts of aging brain. This
      study suggests that hormone replacement therapy may either reduce or delay the
      onset of age related diseases like Alzheimer's, Parkinson's and other
      neurological disorders.

PMID- 16463112
TI  - Chaperones and longevity.
AB  - That evolution of longevity may depend on alterations in the expression of
      relatively few regulatory genes has been inferred from the rapid increase in
      lifespan during evolution of the hominid species (Cutler RG (1979) Mech Ageing
      Dev 9: 337-354). Also the inherent immortality of the embryonic stem cells
      implies that replicative senescence (Hayflick L (1997) Biochem Mosc 62: 1180
      1190) as possibly aging of species are epigenetic phenomena. Evidence is
      presented to suggest that the epigenetic changes of the longevity determinants to
      a significant extend concerns the molecular chaperones. Specific involvement of
      RNA chaperones in cell immortalization and defective RecQ-DNA chaperones in
      syndromes of premature aging suggest that DNA/RNA - chaperones probably rank high
      among the determinants of cellular and species longevity.

PMID- 16463113
TI  - Evolution of human longevity, population pressure and the origins of warfare.
AB  - In a protected environment, humans have the longest lifespan of all primates.
      However, during the emergence of Homo sapiens from pre-hominids, the expectation
      of life at birth would have been quite low. On the basis of reasonable
      assumptions, an average expectation of life of less than 20 years is sufficient
      to maintain a population of hunter-gatherers. As individuals became better
      adapted to their environment, the mortality rate would gradually decrease, and
      this would result in the survival of more offspring to adulthood. Thus, the
      population will increase, and one of the consequences in human evolution is the
      migration of human communities to many new habitats. The development of
      agriculture provided a more reliable source of food, and stimulated further the
      increase in population size. Villages became towns, and then cities, states and
      empires arose which had very large populations, and competed for land and other
      resources. Armies were raised and were often at war. All this was due to
      population pressure, as Malthus had realised more than 200 years ago. However,
      neither he, nor any of the others who discussed warfare, understood that the
      demographic changes that produced large human populations was a steady increase
      in the expectation of life at birth. This inevitably occurred at the same time as
      man gradually gained more control over his environment, and achieved far more
      reproductive success than is seen in hunter-gatherers living in a harsh,
      stressful environment.

PMID- 16463116
TI  - Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal
      cortex and hippocampus.
AB  - Altered expression of Disrupted-In-Schizophrenia-1 (DISC1) and dysbindin
      (DTNBP1), susceptibility genes for schizophrenia, in schizophrenic brain has been
      reported; however, the possible effect of antipsychotics on the expression levels
      of these genes has not yet been studied. We measured the mRNA expression levels
      of these genes in frontal cortex and hippocampus of mice chronically treated with
      typical and atypical antipsychotics by a real-time quantitative RT-PCR method. We
      found that atypical antipsychotics, olanzapine and risperidone, in a clinically
      relevant dose increased DISC1 expression levels in frontal cortex, while a
      typical antipsychotic, haloperidol, did not. No significant effect on dysbindin
      expression levels was observed in either brain region. These data suggest that
      prior evidence of decreased expression of dysbindin in postmortem brain of
      schizophrenics is not likely to be a simple artifact of antemortem drug
      treatment. Our results also suggest a potential role of DISC1 in the therapeutic
      mechanisms of certain atypical antipsychotics.

PMID- 16463115
TI  - Nitric oxide and MPP+-induced hydroxyl radical generation.
AB  - Although neuroprotective effect of nitric oxide (NO) is discussed, NO has a role
      of pathogenesis of cellular injury. NO is synthesized from L-arginine by NO
      synthase (NOS). NO contributes to the extracellular potassium-ion concentration
      ([K(+)](o))-induced hydroxyl radical ((*)OH) generation. Cytotoxic free radicals
      such as peroxinitrite (ONOO(-)) and (*)OH may also be implicated in NO-mediated
      cell injury. NO activation was induced by K(+) depolarization. NO may react with
      superoxide anion (O(2) (-)) to form ONOO(-) and its decomposition generates
      (*)OH. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) metabolite 1-methyl-4
      phenylpyridinium ion (MPP(+)) involve toxicity induced by NO. Intraneuronal
      Ca(2+) triggered by MPP(+) may be detrimental to the functioning of dopaminergic
      nerve terminals in the striatum. Although the [K(+)](o)-induced depolarization
      enhances the formation of (*)OH product due to MPP(+), the (*)OH generation via
      NOS activation may be unrelated the dopamine (DA)-induced (*)OH generation.
      Depolarization enhances the MPP(+)-induced (*)OH formation via NOS activation.
      NOS inhibition is associated with a protective effect due to suppression of
      depolarization-induced (*)OH generation. ONOO(-) has been implicated as a
      causative factor under conditions in which DA neurons are damaged. These findings
      may be useful in elucidating the actual mechanism of free radical formation in
      the pathogenesis of neurodegenerative brain disorders, including Parkinson's
      disease and traumatic brain injuries.

PMID- 16463117
TI  - Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with
      genomic DNA hypermethylation in patients with chronic alcoholism.
AB  - DNA methyltransferases (DNMTs) are involved within the epigenetic control of DNA
      methylation processes. Recently, it has been shown that the genomic DNA
      methylation in patients with alcoholism is increased. In the present controlled
      study we observed a significant decrease of mRNA expression of DNMT-3a and DNMT
      3b when comparing alcoholic patients (n = 59) with healthy controls (n = 66):
      DNMT-3a (t = -2.38, p = 0.019), DNMT-3b (t = -2.65, p = 0.008). No significant
      differences were seen for DNMT-1 and Mbd-2 (Methyl-CpG-Binding-Domain protein 2)
      expression. Additionally, we observed a significant negative correlation between
      DNMT-3b expression and the blood alcohol concentration (r = -0.45, p = 0.003)
      which might explain the decrease of DNMT-3b mRNA expression in alcoholic
      patients. Using a multivariate model we observed that the increase (10%) of
      genomic DNA methylation in patients with alcoholism was significantly associated
      with their lowered DNMT-3b mRNA expression (multiple linear regression, p =
      0.014). Since methylation of DNA is an important epigenetic factor in regulation
      of gene expression these findings may have important implications for a possible
      subsequent derangement of epigenetic control in these patients.

PMID- 16463118
TI  - Personality profile in type I alcoholism: long duration of alcohol intake and low
      serotonergic activity are predictive factors of anxiety proneness.
AB  - The aim of the present study was to further investigate personality profiles in
      male type I alcohol-dependent subjects (n = 33), in relation to central
      serotonergic neurotransmission, history of excessive alcohol consumption and
      present use of tobacco. Central serotonergic neurotransmission was assessed by
      the prolactin (PRL) response to D-fenfluramine. By using the Temperament and
      Character Inventory and the Karolinska Scales of Personality, all subjects self
      rated their personality profile. The results showed that individuals with low PRL
      response and long duration of excessive alcohol consumption had significantly
      higher anxiety proneness, and that years of excessive alcohol consumption was the
      strongest predictor. Long duration of excessive alcohol consumption thus appears
      to have an influence on personality traits in male type I alcohol-dependent
      individuals and these personality traits may therefore be a consequence of,
      rather than preceding, alcoholism in these individuals.

PMID- 16463119
TI  - A simulation model for compensatory plasticity in the prefrontal cortex inducing
      a cortico-cortical dysconnection in early brain development.
AB  - In the present work, an abstract prefrontal cortex simulation model is used to
      predict compensatory structural alterations of the cortico-cortical connectivity
      pattern in the normal and pathologic forebrain maturation. The simulation network
      shows different representative courses of morphogenesis when developing
      undisturbed or when suffering from disturbing excitatory afferences. The
      simulative results could be affirmed by an immuno-histochemical study, revealing
      a qualitatively comparable development of the glutamatergic projection fibre
      density in gerbils (Meriones unguiculatus) after juvenile and adult
      methamphetamine intoxication. The simulation model further allows to consider
      different rearing conditions (enriched-environment model), and claims
      contradictory effects of an equal disturbance after enriched or impoverished
      rearing which are in accordance with the experimental findings.

PMID- 16463121
TI  - Glutamate-induced cell death and formation of radicals can be reduced by lisuride
      in mesencephalic primary cell culture.
AB  - Oxidative stress evoked by excitotoxicity is considered an important factor for
      the loss of dopaminergic neurons in Parkinson's disease. In vitro, protective
      effects of the dopamine agonist lisuride on complex I inhibition in primary
      dopaminergic cell culture have been reported. However, little is known about the
      effects of lisuride on glutamate-induced radical formation. Here, effects of
      lisuride on the formation of nitric oxide (NO) and superoxide radicals following
      glutamate exposure were studied on primary cell cultures prepared from mouse
      mesencephala. Glutamate treatment resulted in doubling of NO and superoxide
      radical formation, increased dopaminergic cell degeneration and extensively
      altered neuronal appearance. Pretreatment with lisuride significantly lowered the
      levels of either reactive species and increased the survival of dopaminergic
      neurons compared to glutamate-treated cultures. Moreover, the beneficial effect
      of lisuride could be completely inhibited by the D2/D3 receptor antagonist
      sulpiride when co-treated in cultures.

PMID- 16463122
TI  - Glutathione peroxidase-1 contributes to the protection of glutamine synthetase in
      astrocytes during oxidative stress.
AB  - Glutamine synthetase (GS) is an astrocytic enzyme that is essential for the
      glutamate-glutamine cycle between neurons and astrocytes. To measure the effects
      of oxidative stress on the activity of GS in astrocytes, astrocyte-rich primary
      cultures from the brains of wild-type and glutathione peroxidase-1 deficient mice
      (GPx1(-/-)) were exposed to a chronic hydrogen peroxide-generating system
      consisting of xanthine oxidase, hypoxanthine and superoxide dismutase. The
      specific activity of GS was strongly diminished by chronic exposure to hydrogen
      peroxide in astrocytes cultured from both mouse lines. After 60 min of oxidative
      stress in the presence of 5 mU/mL, 10 mU/mL and 20 mU/mL of xanthine oxidase, the
      specific GS activity of wild-type astrocytes was reduced to 47%, 22% and 13% of
      the initial activity, respectively. For all activities of xanthine oxidase
      applied, astrocytes from GPx1(-/-) mice experienced a significantly greater rate
      of GS inactivation compared to their wild-type counterparts. These results
      confirm that GS is sensitive to inactivation by chronic peroxide stress in viable
      astrocytes and show that glutathione peroxidase-1 helps to protect GS from
      inactivation by oxidative stress.

PMID- 16463120
TI  - Possible impact of dopamine SPECT on decision-making for drug treatment in
      Parkinsonian syndrome.
AB  - Single-photon emission computed tomography (SPECT) markers allow measuring the
      integrity of the brain dopaminergic system in vivo. We used dopamine transporter
      (DAT) SPECT with [(123)I]FP-CIT and dopamine D(2)/D(3) receptor SPECT with
      [(123)I]IBZM to evaluate whether there is a reduction of DAT and/or D(2)/D(3)
      receptor SPECT in treated and untreated patients with Parkinsonian syndrome (PS).
      We found that almost a quarter of our patients treated with anti-Parkinsonian
      medication prior to SPECT imaging did not show evidence of a presynaptic
      dopaminergic deficit while 37% of untreated patients were diagnosed as having
      Parkinson's disease. 17% of treated patients had additional loss of D(2)/D(3)
      receptor binding capacity in concordance with the clinical follow-up diagnoses of
      multiple system atrophy, progressive nuclear palsy, and vascular Parkinsonism.
      Apart from 38% clinically uncertain cases, SPECT was in concordance with 75% of
      initial clinical diagnoses. 25% were reclassified as indicated by SPECT findings
      and confirmed by a 1.5-year clinical follow-up. We conclude that dopamine SPECT
      may support establishing or refuting the clinical diagnosis and, therefore, help
      to make the decision for or against dopaminomimetic treatment in cases with PS.

PMID- 16463123
TI  - Genetic diversity of noroviruses in Taiwan between November 2004 and March 2005.
AB  - Noroviruses are a major health burden and are responsible for the majority of
      outbreaks of gastroenteritis in the world. Human noroviruses can be genetically
      divided into two main genogroups (GI and GII) and subdivided into many genotypes.
      In this study, stool specimens collected from 12 outbreaks of gastroenteritis in
      Taiwan were screened for viral agents between the 23rd of November 2004 and 9th
      of March 2005. Noroviruses were detected in all outbreaks. We detected six
      different norovirus genotypes: GI/11, GI/14, GII/3, GII/4, GII/6, and GII/18.
      Noroviruses belonging to GII/4 were dominant, 50 of 60 (83%) sequences, and were
      detected in 10 of 12 outbreaks. Furthermore, the norovirus GII/4 strains were
      detected throughout Taiwan, demonstrating their widespread distribution. We also
      found that three outbreaks had noroviruses from multiple genotypes. Our results
      have shown for the first time that noroviruses are an important cause of
      gastroenteritis in Taiwan.

PMID- 16463124
TI  - The complete nucleotide sequence of attenuated onion yellow dwarf virus: a
      natural potyvirus deletion mutant lacking the N-terminal 92 amino acids of HC
      Pro.
AB  - The complete nucleotide sequence of a severe isolate of Onion yellow dwarf virus
      contains 10,459 nucleotides encoding 3,403 amino acids, while that of an
      attenuated isolate contains 10,183 nucleotides encoding 3,311 amino acids. The
      sequence coding for the N-terminal 92 amino acids of HC-Pro was missing in the
      attenuated isolate. Interestingly, garlic plants growing in commercial gardens
      were co-infected with isolates of both types. This is the first report of a
      natural potyvirus deletion mutant lacking the N-terminal region of HC-Pro.

PMID- 16463125
TI  - New temperate DNA phage BcP15 acts as a drug resistance vector.
AB  - This study was designed to determine the role of a new temperate DNA phage BcP15
      in relation to drug resistance. The multidrug resistant Shigella flexneri NK1925
      was isolated from a patient of Infectious Diseases Hospital, Kolkata, India. This
      strain contained five plasmids ranging in size from 3 to 212 kb. After curing of
      five plasmids, this strain became sensitive to antibiotics. A plasmidless
      multidrug-resistant strain Burkholderia cepacia DR11 was isolated during the
      survey of microorganisms from coastal waters of deltaic Sunderbans. This strain
      always released a temperate phage BcP15 into culture supernatant. Turbid plaque
      formation was observed on the lawn of a plasmidless version (Pl(-)35) of Shigella
      flexneri NK1925. A few distinct clones (Pl(-)35R) appeared within the region of
      each plaque after 18 h incubation. S. flexneri NK1925, Pl(-)35, and Pl(-)35R
      clones showed the same PFGE band pattern of XbaI-digested chromosomal DNA.
      However, Pl(-)35R clones were resistant to co-trimoxazole, trimethoprim, and
      eryth- romycin, to which B. cepacia DR11 was also resistant. Southern
      hybridization results indicated that these three antibiotic resistances in Pl(
      )35R clones were due to a BcP15 phage lysogen in the Pl(-)35 version of S.
      flexneri NK1925.

PMID- 16463126
TI  - Whole genome characterization of Potato virus Y isolates collected in the western
      USA and their comparison to isolates from Europe and Canada.
AB  - Potato virus Y (PVY) is a serious potato pathogen that affects potato seed and
      commercial production crops. In recent decades, novel PVY strains have been
      described that cause necrotic symptoms on tobacco foliage and/or potato tubers.
      The major PVY strains that affect potato include PVY(O) and PVY(N), which have
      distinct serotypes that can be differentiated by immunoassay. Other economically
      important strain variants are derived from recombination events, including
      variants that cause tuber necrotic symptoms (PVY(NTN)) and PVY(O) serotypes that
      cause tobacco veinal necrosis (PVY(N)-W, PVY(N:O)). Although the PVY(NTN) and
      PVY(N)-W variants were first reported in Europe, apparently similar strains have
      been appearing in North America. Confirmation of the existence of these
      recombinant strains in North America is important, as is whether they spread from
      a common source or were derived by independent recombination. Whole genome
      sequencing can be used to positively identify strain variants and begin to
      address the issue of origins. Symptomology, serology, RT-PCR, and partial
      sequencing of the coat protein region were used to identify isolates of the
      PVY(NTN), PVY(N), PVY(NA-N), and PVY(N:O) for whole-genome sequencing. Sequencing
      confirmed the presence of PVY(NTN) and PVY(N) isolates that were >99% identical
      to European sequences deposited in GenBank in the 1990's. Sequences of the PVY(NA
      N) and PVY(N:O) types were 99.0% and 99.5% identical to known sequences,
      respectively. There was no indication that recombinant strains PVY(NTN) or
      PVY(N:O) had different parental origins than recombinant strains previously
      sequenced. This is the first confirmation by whole-genome sequencing that
      "European"-type strain variants of PVY(N) and PVY(NTN) are present in North
      America, and the first reported full-length sequence of a tuber necrotic isolate
      of PVY(N:O).

PMID- 16463128
TI  - Left ventricular diastolic dysfunction in children and young adults with Marfan
      syndrome.
AB  - Adults with Marfan syndrome (MFS) demonstrate abnormal aortic elastic properties
      manifest by decreased aortic distensibility and increased aortic stiffness. Left
      ventricular (LV) diastolic dysfunction has been reported in adults with MFS. The
      objective of this study was to assess the frequency of LV diastolic dysfunction
      in a group of children and young adults with MFS and to determine whether
      diastolic dysfunction is associated with hemodynamic alterations of the aorta.
      Review of echocardiographic findings in 40 patients with MFS was performed to
      assess LV size, systolic function, isovolumic relaxation time (IVRT), mitral
      inflow velocities, deceleration time (DT) of mitral E wave, and aortic root
      dimension. No patient had significant valvar disease or was on any cardiac
      medication at the time of study. A group of 40 age and sex-matched healthy
      subjects undergoing echocardiography served as controls. Significant differences
      in LV diastolic function were found between MFS patients and controls. MFS
      patients had prolonged DT and IVRT and decreased mitral E/A ratio, suggesting
      impaired LV relaxation. No relationship between aortic root dimension and
      diastolic performance was identified. Left ventricular diastolic dysfunction may
      be an early marker of myocardial involvement in young MFS patients occurring
      independently of aortic root dilatation.

PMID- 16463127
TI  - Multiple types of cardiac arrhythmias in a child with head injury and raised
      intracranial pressure.
AB  - Arrhythmias occur as a life-threatening complication in adults with severe head
      injuries. A wide spectrum of brady- and tachyarrhythmias and different
      pathogenetic mechanisms have been described. We report an 8-year-old boy with
      traumatic brain injury who developed a variety of independent types of
      arrhythmias during the course of his illness, including supraventricular and
      ventricular extrasystoles, prolonged QT duration and ventricular fibrillation,
      accelerated junctional rhythm, and reentry tachycardia. Each arrhythmia may have
      had a distinct pathogenic pathway, and not all were associated with raised
      intracranial pressure.

PMID- 16463129
TI  - Isolated infundibuloarterial inversion.
AB  - Isolated infundibuloarterial inversion is a rare conotruncal cardiac anomaly
      characterized by a leftward and posterior aortic valve in the face of
      ventriculoarterial concordance. It has previously been described only in cases
      associated with severe additional defects of substantial hemodynamic
      significance. We present a case of isolated infundibuloarterial inversion with a
      small, hemodynamically insignificant ventricular septal defect. The nature of
      this lesion, diagnostic methods of imaging, and features aiding its
      discrimination from the more commonly recognized anatomically corrected
      malposition of the great arteries are discussed.

PMID- 16463130
TI  - Anomalous origin of the left coronary artery from the pulmonary artery in a
      premature infant with preserved left ventricular function.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare condition. The majority of cases present with impaired left ventricular
      function. We report on a premature infant who was diagnosed at a gestational age
      near term with ALCAPA during routine cardiac examination. The patient showed no
      signs of myocardial ischemia and is doing well after corrective surgery. This is
      the youngest patient reported with ALCAPA and preserved myocardial function.

PMID- 16463131
TI  - Denitrification potential in stream sediments impacted by acid mine drainage:
      effects of pH, various electron donors, and iron.
AB  - Acid mine drainage (AMD) contaminates thousands of kilometers of stream in the
      western United States. At the same time, nitrogen loading to many mountain
      watersheds is increasing because of atmospheric deposition of nitrate and
      increased human use. Relatively little is known about nitrogen cycling in acidic,
      heavy-metal-laden streams; however, it has been reported that one key process,
      denitrification, is inhibited under low pH conditions. The objective of this
      research was to investigate the capacity for denitrification in acidified
      streams. Denitrification potential was assessed in sediments from several
      Colorado AMD-impacted streams, ranging from pH 2.60 to 4.54, using microcosm
      incubations with fresh sediment. Added nitrate was immediately reduced to
      nitrogen gas without a lag period, indicating that denitrification enzymes were
      expressed and functional in these systems. First-order denitrification potential
      rate constants varied from 0.046 to 2.964 day(-1). The pH of the microcosm water
      increased between 0.23 and 1.49 pH units during denitrification. Additional
      microcosm studies were conducted to examine the effects of initial pH, various
      electron donors, and iron (added as ferrous and ferric iron). Decreasing initial
      pH decreased denitrification; however, increasing pH had little effect on
      denitrification rates. The addition of ferric and ferrous iron decreased observed
      denitrification potential rate constants. The addition of glucose and natural
      organic matter stimulated denitrification potential. The addition of hydrogen had
      little effect, however, and denitrification activity in the microcosms decreased
      after acetate addition. These results suggest that denitrification can occur in
      AMD streams, and if stimulated within the environment, denitrification might
      reduce acidity.

PMID- 16463132
TI  - Microbial community analysis of soils contaminated with lead, chromium and
      petroleum hydrocarbons.
AB  - The impact on the microbial community of long-term environmental exposure to
      metal and organic contamination was investigated. Twenty-four soil samples were
      collected along a transect dug in soils contaminated with road paint and paint
      solvents, mainly toluene. Chemical analysis along the transect revealed a range
      from high to low concentrations of metals (lead and chromium) and organic solvent
      compounds. Principal components analysis of microbial community structure based
      on denaturing gradient gel electrophoresis of the V3 region of the 16S rRNA gene
      and fatty acid methyl esters derived from phospholipids (phospholipid fatty acid
      analysis) showing samples with similar fingerprints also had similar contaminant
      concentrations. There was also a weak positive correlation between microbial
      biomass and the organic carbon concentration. Results indicated that microbial
      populations are present despite some extreme contaminant levels in this mixed
      waste contaminated site. Nucleotide sequence determination of the 16S rRNA gene
      indicated the presence of phylogenetically diverse bacteria belonging to the
      alpha-, beta-, gamma-, and delta-Proteobacteria, the high and low G + C Gram
      positive bacteria, green nonsulfur, OP8, and others that did not group within a
      described division. This indicates that soils contaminated with both heavy metals
      and hydrocarbons for several decades have undergone changes in community
      composition, but still contain a phylogenetically diverse group of bacteria
      (including novel phylotypes) that warrant further investigation.

PMID- 16463133
TI  - Structure of virioplankton in the Charente Estuary (France): transmission
      electron microscopy versus pulsed field gel electrophoresis.
AB  - Changes in the composition of viral communities were investigated along a
      salinity gradient and at different times by means of transmission electron
      microscopy (TEM) and pulsed field gel electrophoresis (PFGE). Samples were
      collected in fresh (Charente River), estuarine (Charente Estuary), and coastal
      (Pertuis d'Antioche, French Atlantic coast) waters. Both methods revealed similar
      patterns in viral community structure with a dominance of small viral particles
      (capsid and genome size). Viruses with a head size below 65 nm made up 71 +/- 5%
      of total virus-like particles, and virus-like genomes (VLG) below 100 kb
      accounted for 89 +/- 9% of total VLG. Despite this apparent stability of
      virioplankton composition over spatial scale (salinity gradient), the occurrence
      of large viruses (capsid and genome size) in estuarine and seawater samples
      indicated the presence of viral populations specific to a geographical location.
      Temporal changes in the structure (capsid and genome size) of viral communities
      were more pronounced than those reported at the spatial scale. From January to
      May 2003, seasonal changes in viral abundance and bacterial production occurred
      concomitantly with an increase in viral genomic diversity (richness), suggesting
      that virioplankton composition was strongly linked to changes in microbial
      activity and/or in the structure of the host communities. Although PFGE and TEM
      yielded complementary results in the description of virioplankton structures, it
      seems that the use of PFGE alone should be enough for the monitoring of community
      changes.

PMID- 16463134
TI  - Bacterial activity, community structure, and centimeter-scale spatial
      heterogeneity in contaminated soil.
AB  - In an anthropogenically disturbed soil (88% sand, 8% silt, 4% clay), 150-mg
      samples were studied to examine the fine-scale relationship of bacterial activity
      and community structure to heavy metal contaminants. The soils had been
      contaminated for over 40 years with aromatic solvents, Pb, and Cr. Samples from
      distances of <1, 5, 15, and 50 cm over a depth range of 40-90 cm underwent a
      sequential analysis to determine metabolic potential (from 14C glucose
      mineralization), bacterial community structure [using polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE)], and total extractable Pb and
      Cr levels. Metabolic potential varied by as much as 10,000-fold in samples <1 cm
      apart; log-log plots of metal concentration and microbial metabolic potential
      showed no correlation with each other. Overall, metal concentrations ranged from
      9 to 29,000 mg kg(-1) for Pb and from 3 to 8500 mg kg(-1) for Cr with small zones
      of high contamination present. All regions exhibited variable metal
      concentrations, with some soil samples having 30-fold differences in metal
      concentration in sites <1 cm apart. Geostatistical analysis revealed a strong
      spatial dependence for all three parameters tested (metabolic activity, Pb, and
      Cr levels) with a range up to 30 cm. Kriging maps showed that in zones of high
      metal, the corresponding metabolic activity was low suggesting that metals
      negatively impacted the microbial community. PCR-DGGE analysis revealed that
      diverse communities were present in the soils with a random distribution of
      phylotypes throughout the sampling zones. These results suggest the presence of
      spatially isolated microbial communities within the soil profile.

PMID- 16463135
TI  - Useful probability considerations in genetics: the goat problem with tigers and
      other applications of Bayes' theorem.
AB  - Probabilities or risks may change when new information is available. Common sense
      frequently fails in assessing this change. In such cases, Bayes' theorem may be
      applied. It is easy to derive and has abundant applications in biology and
      medicine. Some examples of the application of Bayes' theorem are presented here,
      such as carrier risk estimation in X-chromosomal disorders, maximal manifestation
      probability of a dominant trait with unknown penetrance, combination of genetic
      and non-genetic information, and linkage analysis. The presentation addresses the
      non-specialist who asks for valid and consistent explanations. The conclusion to
      be drawn is that Bayes' theorem is an accessible and helpful tool for probability
      calculations in genetics.

PMID- 16463136
TI  - Stapled endorectal mucosectomy for high extrasphincteric fistula-in-ano:
      preliminary report.
AB  - PURPOSE: There is no optimum surgical method of repair for high extrasphincteric
      fistula-in-ano. We describe a relatively simple procedure for surgery of
      extrasphincteric fistula, which entirely preserves the anal sphincter, does not
      interfere with anal function, and does not preclude the possibility of further
      surgery, if necessary. METHODS: Five patients have been treated for high
      extrasphincteric fistula with a stapled endorectal flap by using a circular
      hemorrhoidal stapler gun. The procedure involved two 180 degrees pursestrings
      placed above the dentate line and 3 cm apart, proximal and distal to the internal
      opening. On firing, the result was the excision of a 180 degrees rectal flap,
      containing the internal ostium, and including rectal mucosa and submucosa.
      RESULTS: No perioperative complications were encountered. There was some
      temporary difficulty in controlling flatus and/or defecatory urgency in two
      patients, which spontaneously reversed with no treatment within the first two
      postoperative months. The mean Cleveland Clinic Score of Incontinence did not
      vary significantly after surgery. Overall anal manometry did not register any
      significant differences between preoperative and postoperative values. With up to
      26 months of follow-up, none of the fistulas recurred. CONCLUSIONS: These
      preliminary promising results suggest that the stapled endorectal flap could have
      a role in the management of high extrasphincteric fistula-in-ano.

PMID- 16463137
TI  - Electrophysiologic studies and clinical findings in females with combined fecal
      and urinary incontinence: a prospective study.
AB  - PURPOSE: Several clinical, urodynamic, and manometric findings suggest neurologic
      damage as a contributing factor in the development of combined fecal and urinary
      incontinence. In this study, we wanted to test the hypothesis of pudendal nerve
      neuropathy being a more frequent lesion in patients with double incontinence
      compared with patients with isolated fecal incontinence. PATIENTS: Ninety-three
      females with combined fecal and urinary incontinence and 36 females with isolated
      fecal incontinence were investigated. All patients underwent anal manometry,
      endoanal ultrasound, electromyography, and pudendal nerve terminal motor latency.
      RESULTS: No statistically significant differences were found in the age, history
      of vaginal delivery, and chronic straining between both groups. However, the rate
      of postmenopausal females was higher in the combined fecal and urinary
      incontinence group (85 vs. 67 percent; P = 0.02). Menopause was an independent
      risk factor of having double incontinence (odds ratio, 1.4; P = 0.02). Concentric
      needle electromyography of the external anal sphincter revealed increased
      duration of the motor unit potentials in 43 and 53 percent of patients with
      combined fecal and urinary incontinence and isolated fecal incontinence,
      respectively (P = 0.28). An increased number of polyphasic motor unit potentials
      was detected in 52 and 58 percent (P = 0.6). There was no statistically
      significant difference in the prevalence of bilateral (20 vs. 27 percent) or
      unilateral (23 vs. 14 percent) prolonged mean pudendal nerve terminal motor
      latency between both groups (P = 0.3). CONCLUSIONS: Pudendal neuropathy is not a
      distinct characteristic of patients with double incontinence. The prevalence of
      pudendal neuropathy in these patients is similar to that observed in patients
      with isolated fecal incontinence. Others factors should be investigated to
      explain the common association of both types of incontinence.

PMID- 16463138
TI  - Interactions of Bax and tBid with lipid monolayers.
AB  - The release of cytochrome c from mitochondria to the cytosol is a crucial step of
      apoptosis that involves interactions of Bax and tBid proteins with the
      mitochondrial membrane. We investigated Bax and tBid interactions with (i)
      phosphatidylcholine (PC) monolayer as the main component of the outer leaflet of
      the outer membrane, (ii) with phosphatidylethanolamine (PE) and
      phosphatidylserine (PS) that are present in the inner leaflet and (iii) with a
      mixed PC/PE/Cardiolipin (CL) monolayer of the contact sites between the outer and
      inner membranes. These interactions were studied by measuring the increase of the
      lipidic monolayer surface pressure induced by the proteins. Our measurements
      suggest that tBid interacts strongly with the POPC/DOPE/CL, whereas Bax
      interaction with this monolayer is about 12 times weaker. Both tBid and Bax
      interact moderately half as strongly with negatively charged DOPS and non
      lamellar DOPE monolayers. TBid also slightly interacts with DOPC. Our results
      suggest that tBid but not Bax interacts with the PC-containing outer membrane.
      Subsequent insertion of these proteins may occur at the PC/PE/CL sites of contact
      between the outer and inner membranes. It was also shown that Bax and tBid being
      mixed in solution inhibit their insertion into POPC/DOPE/CL monolayer. The known
      3-D structures of Bax and Bid allowed us to propose a structural interpretation
      of these experimental results.

PMID- 16463139
TI  - Characterization of regulatory volume behavior by fluorescence quenching in human
      corneal epithelial cells.
AB  - An in-depth understanding of the mechanisms underlying regulatory volume behavior
      in corneal epithelial cells has been in part hampered by the lack of adequate
      methodology for characterizing this phenomenon. Accordingly, we developed a novel
      approach to characterize time-dependent changes in relative cell volume induced
      by anisosmotic challenges in calcein-loaded SV40-immortalized human corneal
      epithelial (HCE) cells with a fluorescence microplate analyzer. During a
      hypertonic challenge, cells shrank rapidly, followed by a temperature-dependent
      regulatory volume increase (RVI), tau(c) = 19 min. In contrast, a hypotonic
      challenge induced a rapid (tau(c) = 2.5 min) regulatory volume decrease (RVD).
      Temperature decline from 37 to 24 degrees C reduced RVI by 59%, but did not
      affect RVD. Bumetanide (50 microM), ouabain (1 mM), DIDS (1 mM), EIPA (100
      microM), or Na(+)-free solution reduced the RVI by 60, 61, 39, 32, and 69%,
      respectively. K+, Cl- channel and K(+)-Cl(-) cotransporter (KCC) inhibition
      obtained with either 4-AP (1 mM), DIDS (1 mM), DIOA (100 microM), high K+ (20 mM)
      or Cl(-)-free solution, suppressed RVD by 42, 47, 34, 52 and 58%, respectively.
      KCC activity also affects steady-state cell volume, since its inhibition or
      stimulation induced relative volume alterations under isotonic conditions. Taken
      together, K+ and Cl- channels in parallel with KCC activity are important
      mediators of RVD, whereas RVI is temperature-dependent and is essentially
      mediated by the Na(+)-K(+)-2Cl(-) cotransporter (Na(+)-K(+)-2Cl(-)) and the Na(+)
      K(+) pump. Inhibition of K+ and Cl- channels and KCC but not Na(+)-K(+)-2Cl(-)
      affect steady-state cell volume under isotonic conditions. This is the first
      report that KCC activity is required for HCE cell volume regulation and
      maintenance of steady-state cell volume.

PMID- 16463140
TI  - ENaC activity requires CFTR channel function independently of phosphorylation in
      sweat duct.
AB  - We previously showed that activation of the cystic fibrosis (CF) transmembrane
      conductance regulator (CFTR) Cl- conductance (gCFTR) supports parallel activation
      of amiloride-sensitive epithelial Na+ channel (ENaC) in the native human sweat
      duct. However, it is not clear whether phosphorylated CFTR, phosphorylated ENaC,
      or only Cl(-) -channel function is required for activation. We used basilaterally
      alpha-toxin-permeabilized human sweat ducts to test the hypothesis that ENaC
      activation depends only on Cl(-) -channel function and not on phosphorylation of
      either CFTR or ENaC. CFTR is classically activated by PKA plus millimolar ATP,
      but cytosolic glutamate activation of gCFTR is independent of ATP and
      phosphorylation. We show here that both phosphorylation-dependent (PKA) and
      phosphorylation-independent (glutamate) activation of CFTR Cl- channel function
      support gENaC activation. We tested whether cytosolic application of 5 mM ATP
      alone, phosphorylation by cAMP, cGMP, G-protein dependent kinases (all in the
      presence of 100 microM ATP), or glutamate could support ENaC activation in the
      absence of gCFTR. We found that none of these agonists activated gENaC by
      themselves when Cl- current (I(Cl-)) through CFTR was blocked by: 1) Cl- removal,
      2) DIDS inhibition, 3) lowering the ATP concentration to 100 microM (instead of 5
      mM required to support CFTR channel function), or 4) mutant CFTR (homozygous
      DeltaF508 CF ducts). However, Cl- gradients in the direction of absorption
      supported, while Cl- gradients in the direction of secretion prevented ENaC
      activation. We conclude that the interaction between CFTR and ENaC is dependent
      on activated I(Cl-) through CFTR in the direction of absorption (Cl- gradient
      from lumen to cell). But such activation of ENaC is independent of
      phosphorylation and ATP. However, reversing I(Cl-) through CFTR in the direction
      of secretion (Cl- gradient from cell to lumen) prevents ENaC activation even in
      the presence of I(Cl-) through CFTR.

PMID- 16463141
TI  - State-dependent block of human cardiac hNav1.5 sodium channels by propafenone.
AB  - State-dependent blockade of human cardiac hNav1.5 sodium channels by propafenone
      was studied using whole-cell patch clamp techniques. Both a direct investigation
      using cells with inactivation-deficient sodium channels and an algorithmic
      approach used on cells with wild-type channels revealed a rapid binding of
      propafenone to the open state. This occurs approximately 4000 and 700 times
      faster than the binding to the resting and inactivated state, respectively. An
      established mathematical "gating" model was modified to represent the
      experimental data.

PMID- 16463143
TI  - Non-transferable signals on ant queen eggs.
AB  - How biological systems resolve internal conflicts is a major evolutionary
      question. Social insect workers cooperate but also pursue individual interests,
      such as laying male eggs. The rewards of this individual selfishness can be
      reduced by policing, such as by killing worker-laid eggs. However, selfish
      individuals may evade policing. What factors prevent individuals from being able
      to evade policing? In the ant Pachycondyla inversa, workers kill (police) worker
      laid eggs. Because the colony keeps eggs in piles and worker-laid and queen-laid
      eggs are chemically distinct, worker-laid eggs might become more acceptable once
      placed in the egg pile by odour transfer from touching queen-laid eggs. Here, we
      show that such "cue scrambling" does not occur. Worker-laid eggs that were
      sandwiched between three queen-laid eggs for 45 min were not more acceptable in a
      policing bioassay than control worker-laid eggs. Chemical analyses also showed
      that the surface hydrocarbon profile of these eggs was unchanged. Policing,
      therefore, is stable against this potential cheating mechanism probably because
      queen-laid eggs are made chemically distinct using chemicals, that are not easily
      transferred by physical contact.

PMID- 16463144
TI  - Right renal stone on the trajectory of upper left ureter.
AB  - We report a 52-year-old woman with a right renal pelvic stone, mimicking a left
      upper ureteral stone in a kidney-ureter-bladder film. Computed tomography
      detected the exact anatomical location of the stone, which was not possible by
      intravenous urography and ultrasonography. In this study, we discuss diagnostic
      modalities of the urinary calculi in the light of the literature.

PMID- 16463142
TI  - Association with ZO-1 correlates with plasma membrane partitioning in truncated
      connexin45 mutants.
AB  - Zonula occludens-1 (ZO-1), the most abundant known connexin-interacting protein
      in osteoblastic cells, associates with the carboxyl termini of both Cx43 and
      Cx45. To learn more about the role of the cormexin-ZO-1 interaction, we analyzed
      connexin trafficking and function in ROS 17/2.8 cells that were stably
      transfected either with full length Cx45 or with Cx45 lacking 34 or 37 amino
      acids on the carboxyl terminus (Cx45t34 or Cx45t37). All three proteins were
      transported to appositional membranes in the transfected cells: Cx45 and Cx45t34
      displayed a punctate appositional membrane-staining pattern, while Cx45t37
      staining at appositional membranes was more linear. Expression of Cx45 decreased
      gap junction communication as assayed by dye transfer, while expression of
      Cx45t34 or Cx45t37 increased the amount of dye transfer seen in these cells. We
      found that Cx43, Cx45 and Cx45t34 co-precipitated with ZO-1 in these cells, while
      Cx45t37 did not. We also found that Cx45t37 was much more soluble in 1% Triton X
      100 than the other connexins examined. In addition, Cx45t37 migrated to a
      fraction of lighter buoyant density on sucrose flotation gradients than Cx43,
      Cx45, ZO-1 and Cx45t34. As ZO-1 is an actin-binding protein, this suggested that
      the differences in Cx45t37 solubility might be due to a difference between the
      interaction of gap junctions and the actin cytoskeleton in the ROS/Cx45t37 and in
      the other transfected ROS cells. To examine this possibility, the transfected ROS
      cells were stained with fluorescently labeled phalloidin and demonstrated that
      there was a notable loss of actin stress fibers in the ROS/Cx45t37 cells. These
      findings suggest that association with ZO-1 alters the plasma membrane
      localization of Cx45 by removing it from a lipid raft compartment and rendering
      it Triton-insoluble, presumably by promoting an interaction with the actin
      cytoskeleton; they also suggest that Cx45 has a complex binding interaction with
      ZO-1 that involves either an extended carboxyl terminal domain or two distinct
      binding sites.

PMID- 16463145
TI  - Management of lower pole renal calculi: shock wave lithotripsy versus
      percutaneous nephrolithotomy versus flexible ureteroscopy.
AB  - Current ureteroscopic intracorporeal lithotripsy devices and stone retrieval
      technology allow for the treatment of calculi located throughout the intra-renal
      collecting system. Difficulty accessing lower pole calculi, especially when the
      holmium laser fiber is utilized, is often encountered. Herein we review our
      experience where lower pole renal calculi were ureteroscopically managed by
      holmium laser fragmentation, either in situ, or by first displacing the stone
      into a less dependent position with the aid of a nitinol stone retrieval device.
      Lower pole stones less than 20 mm can be primarily treated by ureteroscopic means
      in patients: that are obese; have a bleeding diathesis; with stones resistant to
      shockwave lithotripsy (SWL); with complicated intra-renal anatomy; or as a
      salvage procedure after failed SWL. Lower pole calculi are fragmented with a 200
      microm holmium laser fiber via a 7.5 F flexible ureteroscope. For those patients
      where the laser fiber reduced ureteroscopic deflection, precluding re-entry into
      the lower pole calyx, a 1.9 F nitinol basket is used to displace the lower pole
      calculus into a more favorable position, thus allowing for easier fragmentation.
      A nitinol device passed into the lower pole, through the ureteroscope, for stone
      displacement cause only a minimal loss of deflection and no significant impact on
      irrigation. Eighty-five percent of patients were stone free by IVP or CT scan
      performed at 3 months. Ureteroscopic management of lower pole calculi is a
      reasonable alternative to SWL or percutaneous nephrolithotomy (PNL) in patients
      with low volume stone disease. If the stone cannot be fragmented in situ, nitinol
      basket or grasper retrieval, through a fully deflected ureteroscope, allows for
      repositioning of the stone into a less dependant position, thus facilitating
      stone fragmentation.

PMID- 16463146
TI  - Conserved domains control heterochromatin localization and silencing properties
      of SU(VAR)3-7.
AB  - The Drosophila protein SU(VAR)3-7 is essential for fly viability, chromosome
      structure, and heterochromatin formation. We report that searches in silico and
      in vitro for homologues of SU(VAR)3-7 were successful within, but not outside,
      the Drosophila genus. Protein sequence homology between the distant sibling
      species Drosophila melanogaster and Drosophila virilis is low, except for the
      general organization of the protein and three conserved motives: seven widely
      spaced zinc fingers in the N-terminal half and the BESS and BoxA motives in the C
      terminal half of the protein. We have undertaken a fine functional dissection of
      SU(VAR)3-7 in vivo using transgenes encoding truncations of the protein. BESS
      mediates interaction of SU(VAR)3-7 with itself, and BoxA is required for specific
      heterochromatin association. Both are necessary for the silencing properties of
      SU(VAR)3-7. The seven zinc fingers, widely spaced over the N-terminal half of
      SU(VAR)3-7, are required for binding to polytene chromosomes. One finger is
      necessary and sufficient to determine the appropriate chromatin association of
      the C-terminal half of the protein. Conferring a function to each of the
      conserved motives allows us to better understand the mode of action of SU(VAR)3-7
      in triggering heterochromatin formation and subsequent genomic silencing.

PMID- 16463147
TI  - Is the risk for secondary cancers after proton therapy enhanced distal to the
      Planning Target Volume? A two-case report with possible explanations.
AB  - It is often assumed that radiation-induced secondary cancer after proton therapy
      forms preferentially close to the distal fall-off of the spread-out Bragg peak
      because of an increased relative biological effectiveness (RBE) with regard to
      cancer induction of low-energy protons. In this study we analyze to what extent
      dose gradients distal to the Planning Target Volume (PTV) may, independently from
      the RBE, contribute to enhanced radiation carcinogenesis. The study is based on
      two dogs which, out of 30 dogs treated with proton therapy at the Paul Scherrer
      Institute (PSI), developed a secondary cancer. Both dogs were originally
      diagnosed and treated for a fibrosarcoma and developed an osteosarcoma 48 and
      almost 60 months, respectively, after radiotherapy. From the dose distributions
      of the initial radiotherapy for both dogs three-dimensional maps of secondary
      cancer complication probability (SCCP) were computed. The SCCP maps were analyzed
      in the regions where the dogs developed a secondary cancer. The SCCP maps showed
      an enhanced risk in the regions of the femur where the secondary cancers were
      detected, as compared to the SCCP of the total femur. Excess risk of radiation
      induced cancer at the distal part of proton radiation fields can thus be
      explained using SCCP calculations on the basis of the physical dose
      distributions. Therefore, the occurrence of secondary cancer close to the distal
      dose gradients of proton therapy is not necessarily due to an increased RBE of
      low-energy protons. More extensive studies based on more patients will be
      necessary to further elucidate the factors influencing the development of
      secondary tumors.

PMID- 16463148
TI  - Neurogenesis and neuronal regeneration in the adult fish brain.
AB  - Fish are distinctive in their enormous potential to continuously produce new
      neurons in the adult brain, whereas in mammals adult neurogenesis is restricted
      to the olfactory bulb and the hippocampus. In fish new neurons are not only
      generated in structures homologous to those two regions, but also in dozens of
      other brain areas. In some regions of the fish brain, such as the optic tectum,
      the new cells remain near the proliferation zones in the course of their further
      development. In others, as in most subdivisions of the cerebellum, they migrate,
      often guided by radial glial fibers, to specific target areas. Approximately 50%
      of the young cells undergo apoptotic cell death, whereas the others survive for
      the rest of the fish's life. A large number of the surviving cells differentiate
      into neurons. Two key factors enabling highly efficient brain repair in fish
      after injuries involve the elimination of damaged cells by apoptosis (instead of
      necrosis, the dominant type of cell death in mammals) and the replacement of
      cells lost to injury by newly generated ones. Proteome analysis has suggested
      well over 100 proteins, including two dozen identified ones, to be involved in
      the individual steps of this phenomenon of neuronal regeneration.

PMID- 16463150
TI  - Asymmetries of long-latency intracortical inhibition in motor cortex and
      handedness.
AB  - Paired-pulse transcranial magnetic stimulation was used in three experiments to
      measure the properties of long-latency intracortical inhibition (LICI) acting on
      the relaxed first dorsal interosseus muscle of the left and right hand in right
      handed volunteers. The experiments show that LICI is asymmetrical: it emerges
      more rapidly and is greater in the dominant than non-dominant hand shortly after
      activation of the LICI circuits, and is greater with low-intensity conditioning
      stimulus intensities in the dominant than non-dominant hand. These findings
      suggest that asymmetrical function of long-latency inhibitory circuits in motor
      cortex might contribute to the asymmetrical dexterity between the hands, possibly
      through their inhibitory control of the circuits responsible for short-latency
      inhibition.

PMID- 16463149
TI  - Subcortical reorganization in amyotrophic lateral sclerosis.
AB  - The cerebral cortex reorganizes in response to central or peripheral lesions.
      Although basal ganglia and cerebellum are key components of the network dedicated
      to movement control, their role in motor reorganization remains elusive. We
      therefore tested if slowly progressive neurodegenerative motor disease alters the
      subcortical functional anatomy of the basal ganglia-thalamo-cerebellar circuitry.
      Ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls
      underwent functional magnetic resonance imaging (fMRI), while executing a simple
      finger flexion task. Cued by an acoustic trigger, they squeezed a handgrip force
      transducer with their right hand at 10% of their maximum voluntary contraction
      force. Movement frequency, amplitude, and force were controlled. Statistical
      parametric mapping of task-related BOLD-response revealed increased activation in
      ALS patients as compared to healthy controls. The main activation increases were
      found in the supplementary motor area, basal ganglia, brainstem, and cerebellum.
      These findings suggest that degeneration of cortical and spinal motor neurons in
      ALS leads to a recruitment of subcortical motor structures. These subcortical
      activation patterns strongly resemble functional activation in motor learning and
      might therefore represent adaptations of cortico-subcortical motor loops as a -
      albeit finally ineffective - mechanism to compensate for the ongoing loss of
      motor neurons in ALS.

PMID- 16463152
TI  - CT for suspected appendicitis in children: an analysis of diagnostic errors.
AB  - BACKGROUND: Mistakes have been made by the use of CT in diagnosing children with
      suspected appendicitis. Although others have reported the frequency of diagnostic
      errors, we were unable to find any studies that addressed the specific situations
      in which diagnostic errors occurred in children with suspected appendicitis.
      OBJECTIVE: To investigate the frequency and type of diagnostic errors resulting
      from CT of children with suspected appendicitis when compared to surgical and
      pathological diagnosis. MATERIALS AND METHODS: We reviewed imaging, clinical and
      pathological data on 1,207 consecutive pediatric patients who underwent CT
      examination for suspected appendicitis. Imaging findings were categorized as
      false-positive, false-negative, or indeterminate. Errors were classified as
      interpretative, technical or unavoidable. Concordance between surgical and
      pathological findings was also evaluated. RESULTS: The imaging findings of 34
      patients (2.8%) were discrepant with the pathological examination or clinical
      follow-up. The errors in 23 cases were classified as interpretive (68%) and 11 as
      unavoidable (32%), and no errors were classified as technical. There were 23
      false-positive errors (68%), 6 false-negative errors (18%), and 5 indeterminate
      imaging studies (15%). Isolated CT findings of an enlarged (greater than 6 mm)
      appendix, fat stranding, thickened bowel or non-visualization of the distal
      appendix were the most common false-positive CT findings. Of these 34 patients,
      22 underwent appendectomy, with 10 (45%) having discordant surgical and
      pathological findings. CONCLUSIONS: Isolated CT findings of an appendicolith, an
      enlarged appendix, or minimal fat stranding are not sufficient signs for the
      diagnosis of appendicitis. Pathological diagnosis rather than surgical findings
      should be used as the reference standard of true-positive imaging findings.

PMID- 16463151
TI  - Subjective somatosensory vertical during dynamic tilt is dependent on task,
      inertial condition, and multisensory concordance.
AB  - To investigate how visual and vestibular cues are integrated for the perception
      of gravity during passive self-motion, we measured the ability to maintain a
      handheld object vertical relative to gravity without visual feedback during
      sinusoidal roll-tilt stimulation. Visual input, either concordant or discordant
      with actual dynamic roll-tilt, was delivered by a head-mounted display showing
      the laboratory. The four visual conditions were darkness, visual-vestibular
      concordance, stationary visual scene, and a visual scene 180 degrees phase
      shifted relative to actual tilt. Tilt-indication performance using a solid,
      cylindrical joystick was better in the presence of concordant visual input
      relative to the other visual conditions. In addition, we compared performance
      when indicating the vertical by the joystick or a full glass of water. Subjects
      indicated the direction of gravity significantly better when holding the full
      glass of water than the joystick. Matching the inertial characteristics,
      including fluid properties, of the handheld object to the glass of water did not
      improve performance. There was no effect of visual input on tilt performance when
      using the glass of water to indicate gravitational vertical. The gain of object
      tilt motion did not change with roll-tilt amplitude and frequency (+/-7.5 degrees
      at 0.25 Hz, +/-10 degrees at 0.16 Hz, and +/-20 degrees at 0.08 Hz), however, the
      phase of object tilt relative to subject tilt showed significant phase-leads at
      the highest frequency tested (0.25 Hz). Comparison of the object and visual
      effects observed suggest that the task-dependent behavior change may be due to an
      attentional shift and/or shift in strategy.

PMID- 16463154
TI  - The prevalence and diagnostic value of toxocariasis in unknown eosinophilia.
AB  - Toxocariasis is one of the causes of eosinophilia in peripheral blood and
      provokes eosinophilic infiltration in internal organs. Extended studies on the
      prevalence and clinical characteristics of toxocariasis have been rare. The aim
      of this study is to evaluate the prevalence of toxocariasis in unknown
      eosinophilia and to analyze the efficacy of toxocara enzyme-linked immunosorbent
      assay (ELISA). We evaluated patients presenting with peripheral blood
      eosinophilia (>500 cells/microl or > or =10% of white blood cell count). After
      checking drug histories and the presence of allergic diseases and parasitic
      infections, specific serum IgG antibody to Toxocara canis larval antigen was
      measured by ELISA. Liver and lung involvement was also evaluated. One-hundred and
      three patients were evaluated, and the mean age was 50.9 years old. Seventy
      patients (68.0%) were diagnosed as having toxocariasis. The patients who had a
      history of raw liver eating had a higher incidence, and the patients with liver
      involvement had higher serum eosinophil cationic protein values. The eosinophil
      count was normalized in 7 of 16 treated patients and in 25 of 54 untreated
      patients. The mean improvement duration was 12 months. We concluded that the
      prevalence of toxocariasis was high in patients with unknown eosinophilia, and
      the toxocara ELISA was essential for evaluation of the causes of unknown
      eosinophilia.

PMID- 16463155
TI  - Acute splenic sequestration crisis in adults with hemoglobin S-C disease: a
      report of nine cases.
AB  - Acute splenic sequestration crisis (ASSC) is a potentially life-threatening
      complication and one of the leading causes of death in children with sickle cell
      disease. It is rarely reported in adults with hemoglobin S-C disease and its
      natural history in these patients has not been well studied. We describe here the
      clinicopathological features of ASSC in nine adults with hemoglobin S-C disease
      treated between 1972 and 2000 and followed for a mean period of 9 years (range 0
      21 years). ASSC was characterized by acute left upper quadrant abdominal pain,
      splenomegaly, fever, and a rapid decrease in hematocrit with active
      erythropoiesis. The hemoglobin decreased by a mean of 4.8 g/dl from the steady
      state value (range 3.0 to 6.7 g/dl) during ASSC. Two patients failed to respond
      to transfusion of packed erythrocytes and required urgent splenectomy. There was
      one fatality-a 76-year-old woman, who died 36 h after admission. There was no
      recurrence of ASSC in five patients followed for 2, 3, 16, 18, and 21 years,
      respectively. ASSC in adults is a serious and occasionally, fatal complication of
      hemoglobin S-C disease. Patients with hemoglobin S-C disease may remain at risk
      of ASSC into their eighth decade.

PMID- 16463153
TI  - MTHFR 677 (C-->T) polymorphism is not relevant for prognosis or therapy
      associated toxicity in pediatric NHL: results from 484 patients of multicenter
      trial NHL-BFM 95.
AB  - We analyzed the relationship of genetic variation within the
      methylenetetrahydrofolate reductase gene (MTHFR 677 C-->T) with clinical
      characteristics, outcome, and therapy-related toxicity in pediatric non-Hodgkin's
      lymphoma (NHL) in our multicenter trial NHL-BFM 95. In this trial, high-dose
      methotrexate (MTX) infusion regimens were randomized (4- vs 24-h infusion) in
      patients with B-cell lymphoma; MTX was applied as 24-h infusion in all patients
      with lymphoblastic lymphoma and anaplastic large cell lymphoma. Toxicity data
      were collected per patient and therapy course according to National Cancer
      Institute Common Toxicity Criteria (NCI-CTC). The genotypes in 484 pediatric
      patients were distributed as follows: MTHFR 677 CC, 206 patients (42.6%); MTHFR
      677 CT, 214 patients (44.2%); and MTHFR 677 TT, 64 patients (13.2%).
      Lymphoblastic lymphoma was significantly associated with homozygosity for the
      MTHFR 677 T allele. No association of MTHFR 677 genotype with clinical
      characteristics (sex, age, and tumor stage), outcome, or therapy-related toxicity
      could be detected. Therefore, we conclude that the MTHFR 677 C-->T polymorphism
      does not appear to influence outcome or therapy-associated toxicity in pediatric
      patients with NHL treated on BFM protocols.

PMID- 16463156
TI  - Value of proteomics applied to the follow-up in stem cell transplantation.
AB  - Proteome analysis is now emerging as an important technology for deciphering
      biological processes and the discovery of biomarkers for diseases from tissues
      and body fluids. Polypeptides found in body fluids are responsible for the flow
      of information from cells and tissues, and the changes of the expression of these
      vehicles may give insight in different states of health and disease. Thus, body
      fluids obtained from patients are particularly interesting for monitoring of
      disease, disease progression, and responsiveness to therapy. The complexity and
      the wide dynamic range of protein expression pose an enormous challenge to both
      protein/peptide separation technologies and the following identification tools,
      mainly mass spectrometry (MS). In this paper, we review the application of
      proteomic screening to the early detection of acute graft vs host disease after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). We discuss
      proteomic screening of clinical samples focusing on the two most important
      methods, namely, "surface-enhanced laser desorption/ionization" (SELDI)-MS and
      "capillary zone electrophoresis" (CE)-MS, from an application point of view,
      evaluating its merits and vices with regard to biomarker discovery and the
      benefits in clinical application. As an example, we describe the use of CE-MS for
      the determination of protein patterns in urine. Finally, the benefits and
      limitations of CE-MS for the analysis of proteins in the follow up of patients
      after HSCT are discussed against the background of alternative technologies.

PMID- 16463157
TI  - Molecular cytogenetics and DNA sequence analysis of an apomixis-linked BAC in
      Paspalum simplex reveal a non pericentromere location and partial
      microcolinearity with rice.
AB  - Apomixis in plants is a form of clonal reproduction through seeds. A BAC clone
      linked to apomictic reproduction in Paspalum simplex was used to locate the
      apomixis locus on meiotic chromosome preparations. Fluorescent in situ
      hybridisation revealed the existence of a single locus embedded in a
      heterochromatin-poor region not adjacent to the centromere. We report here for
      the first time information regarding the sequencing of a large DNA clone from the
      apomixis locus. The presence of two genes whose rice homologs were mapped on the
      telomeric part of the long arm of rice chromosome 12 confirmed the strong synteny
      between the apomixis locus of P. simplex with the related area of the rice genome
      at the map level. Comparative analysis of this region with rice as representative
      of a sexual species revealed large-scale rearrangements due to transposable
      elements and small-scale rearrangements due to deletions and single point
      mutations. Both types of rearrangements induced the loss of coding capacity of
      large portions of the "apomictic" genes compared to their rice homologs. Our
      results are discussed in relation to the use of rice genome data for positional
      cloning of apomixis genes and to the possible role of rearranged supernumerary
      genes in the apomictic process of P. simplex.

PMID- 16463158
TI  - Lack of evidence for association between endothelial nitric oxide synthase gene
      polymorphism (glu298asp) with Behcet's disease in the Turkish population.
AB  - Endothelial nitric oxide synthase (eNOS) could be a candidate gene for Behcet's
      disease (BD). This study investigated the relationship of the eNOS Glu298 --> Asp
      polymorphism with the presence and severity of BD in the Turkish population.
      Ninety-two patients with BD and 100 controls were studied. Analyses of Glu298Asp
      polymorphism in exon 7 of the eNOS gene were made by the polymerase chain
      reaction (PCR)-restriction fragment length polymorphism technique. The
      frequencies of the eNOS genotypes were similar for BD patients (GG:GT:TT =
      58.7%:38%:3.3%) and controls (59.2%:33.7%:7.1 %), P = 0.335. No evidence of
      difference was found in the frequency of the T allele between BD patients (22.3%)
      and controls (24%), [OR = 0.91, 95% CI (0.55-1.50), P = 0.690]. Glu298 --> Asp
      polymorphism of the eNOS gene does not appear to be associated with the presence
      of BD in the Turkish population.

PMID- 16463159
TI  - Methyl jasmonate and salicylic acid elicitation induces ginsenosides
      accumulation, enzymatic and non-enzymatic antioxidant in suspension culture Panax
      ginseng roots in bioreactors.
AB  - The effects of methyl jasmonate (MJ) and salicylic acid (SA) on changes of the
      activities of major antioxidant enzymes, superoxide anion accumulation (O2-),
      ascorbate, total glutathione (TG), malondialdehyde (MDA) content and ginsenoside
      accumulation were investigated in ginseng roots (Panax ginseng L.) in 4 l
      (working volume) air lift bioreactors. Single treatment of 200 microM MJ and SA
      to P. ginseng roots enhanced ginsenoside accumulation compared to the control and
      harvested 3, 5, 7 and 9 days after treatment. MJ and SA treatment induced an
      oxidative stress in P. ginseng roots, as shown by an increase in lipid
      peroxidation due to rise in O2- accumulation. Activity of superoxide dismutase
      (SOD) was inhibited in MJ-treated roots, while the activities of
      monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), SOD,
      guaiacol peroxidase (G-POD), glutathione peroxidase (GPx) and glutathione
      reductase (GR) were induced in SA-treated roots. A strong decrease in the
      activity of catalase (CAT) was obtained in both MJ- and SA-treated roots.
      Activities of ascorbate peroxidase (APX) and glutathione S transferase (GST) were
      higher in MJ than SA while the contents of reduced ascorbate (ASC), redox state
      (ASC/(ASC+DHA)) and TG were higher in SA- than MJ-treated roots while oxidized
      ascorbate (DHA) decreased in both cases. The result of these analyses suggests
      that roots are better protected against the O2- stress, thus mitigating MJ and SA
      stress. The information obtained in this work is useful for efficient large-scale
      production of ginsenoside by plant-root cultures.

PMID- 16463160
TI  - A microplate spectrofluorometric assay for bacterial biofilms.
AB  - A spectrofluorometric assay was developed for quantification of bacterial
      biofilms grown on a microtiter plate. The method involved staining biofilms
      formed by gram-negative and gram-positive bacteria with wheat germ agglutinin
      Alexa Fluor 488 conjugate, which selectively binds to N-acetylglucosamine
      residues in biofilms. The fluorescence of stained biofilms was measured with a
      fluorescent plate reader. This method was compared with a widely used microplate
      colorimetric assay involving crystal violet staining of biofilms formed by both
      gram-negative and gram-positive bacteria. A strong linear association existed
      between the two methods (r (2)=0.99/0.94). Being more sensitive and specific as
      compared to colorimetric method, the spectrofluorometric assay provides a better
      alternative for quantification and characterization of bacterial biofilms.

PMID- 16463161
TI  - Antibiotic production by actinomycetes: the Janus faces of regulation.
AB  - This manuscript reviews some of the common regulatory mechanisms that control
      antibiotic production in actinomycetes. These ubiquitous bacteria, collectively
      responsible for the earthy smell of soil, are prolific producers of antibiotics
      and other secondary metabolites. The content of this review is biased towards the
      author's current research interests, concerning the action of regulatory gene
      products that control transcription of antibiotic-biosynthetic genes and the
      associated involvement of low molecular weight signalling molecules of the gamma
      butyrolactone family. As a result, much fertile ground remains unturned
      particularly in the area of environmental monitoring and responses of
      actinomycetes to stimuli so perceived. Reviews casting a broader net are cited in
      the text.

PMID- 16463162
TI  - Exopolysaccharides production in Lactobacillus bulgaricus and Lactobacillus casei
      exploiting microfiltration.
AB  - The physiology of Lactobacillus delbrueckii ssp. bulgaricus and Lactobacillus
      casei, extensively used in the dairy industry, was studied in order to evaluate
      key parameters in the synthesis of exopolysaccharides and to improve their
      production through novel fermentation processes. Selected strains were studied in
      shake flasks and in fermentor experiments using glucose and lactose as main
      carbon sources and bacto casitone as the only complex component, in a temperature
      range between 35 and 42 degrees C. The production of exopolysaccharides was
      monitored and correlated to the growth conditions using both a colorimetric assay
      and chromatographic methods. Fermentor experiments in batch mode yielded 100 mg
      l(-1) of EPS from L. bulgaricus and 350 mg l(-1) from L. casei. Moreover, the use
      of a microfiltration (MF) bioreactor resulted in exopolysaccharides (EPS)
      concentrations threefold and sixfold those of batch experiments, respectively.
      The monosaccharidic composition of the two analyzed polymers differed from those
      previously reported. The optimization of the production of EPSs using the MF
      fermentation strategy could permit the use of these molecules produced by
      generally recognised as safe (GRAS) microorganisms in the place of other
      polysaccharides in the food industry.

PMID- 16463163
TI  - Pregnancy complications in women with inherited thrombophilia.
AB  - OBJECTIVE: The purpose of this study was to examine whether women with inherited
      thrombophilia have an increased risk of developing pregnancy complications.
      METHODS: All singleton pregnancies with known inherited thrombophilia were
      compared to those without inherited thrombophilia for deliveries during the years
      2000-2002 in a tertiary medical center. Data regarding inherited thrombophilia
      (International Classification of Disease 9th revision, Clinical Modification code
      286.3) were available from the perinatal database in our center. Women lacking
      prenatal care were excluded from the analysis. Stratified analysis, using a
      multiple logistic regression model, was performed to control for confounders.
      RESULTS: Out of 32,763 singleton deliveries that occurred during the study
      period, 0.2% (n=57) of the women were diagnosed with inherited thrombophilia.
      Using a multivariate analysis, with backward elimination, the following
      conditions were significantly associated with inherited thrombophilia: previous
      fetal losses [odds ratio (OR)=5.5; 95% confidence interval (CI) 2.9-10.3;
      P<0.001], recurrent abortions (OR=9.5; 95% CI 5.5-16.3; P<0.001), fertility
      treatments (OR=3.7; 95% CI 1.3-10.6; P=0.014), and intrauterine growth
      restriction (OR=7.2; 95% CI 3.4-15; P<0.001). Perinatal mortality was
      significantly higher in women with inherited thrombophilia than in those without
      known thrombophilia 5.3% (3/57) versus 0.6% (477/32,763) P=0.017. However,
      inherited thrombophilia was not found to be an independent risk factor for
      perinatal mortality (OR=3.05; 95% CI 0.90-10.3; P<0.073) in a multivariate
      analysis with perinatal mortality as the outcome variable, controlling for
      recurrent abortions, IUGR, and gestational age. CONCLUSION: Inherited
      thrombophilia, associated with previous fetal losses, recurrent abortions,
      fertility treatments, and intrauterine growth restriction, was not an independent
      risk factor for perinatal mortality.

PMID- 16463164
TI  - Magnetic resonance imaging in the evaluation of uterus didelphys with obstructed
      hemivagina and renal agenesis: a case report.
AB  - Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis
      usually presents after menarche with progressive abdominal pain during menses
      secondary to hematocolpos. Initially, the anomaly remains unrecognized, while
      patients most frequently referred to surgeons for assistance. The method of
      choice for diagnosis is magnetic resonance imaging. A greater awareness of the
      syndrome of uterus didelphys, obstructed hemivagina and ipsilateral renal
      agenesis should lead to its prompt diagnosis, allowing for early and appropriate
      surgical treatment as well as decreased long-term morbidity. Transvaginal
      excision of the septum is the appropriate mode of treatment.

PMID- 16463165
TI  - Labor analgesia for the parturient with neurological disease: what does an
      obstetrician need to know?
AB  - Several neurological disorders including multiple sclerosis, myasthenia gravis,
      epilepsy, spinal cord injury, and subarachnoid hemorrhage are encountered with
      increasing frequency in pregnant women worldwide. Although there is absence of
      uniform anesthetic guidelines for pregnant patients with most of these (and
      other) neurological disorders, and the decision whether or not to administer
      regional anesthesia is based on an individual risk-to-benefit ratio on a case-by
      case basis, few of these disorders contraindicate the use of neuraxial
      anesthesia. This article attempts to review the specific concerns for
      administration of labor analgesia posed by multiple sclerosis, myasthenia gravis,
      epilepsy, paraplegia and subarachnoid hemorrhage.

PMID- 16463166
TI  - Emergency peripartum hysterectomy: a 9-year review.
AB  - OBJECTIVE: To determine the incidence, indications, risk factors, and
      complications of emergency peripartum hysterectomy. STUDY DESIGN: A retrospective
      study of the patients requiring an emergency peripartum hysterectomy of a 9-year
      period was conducted. Emergency peripartum hysterectomy was defined as one
      performed for hemorrhage unresponsive to other treatment less than 24 h after
      delivery. Demographic and clinical variables were obtained from the maternal
      records. RESULTS: There were 34 emergency peripartum hysterectomies out of
      117,095 deliveries for a rate of 0.29 per 1,000. Of the 16 cases that were
      delivered by cesarean section, seven had a previous cesarean section and 18 cases
      were delivered vaginally, including two using vacuum extraction. Total
      hysterectomy was performed in 24 patients, and subtotal hysterectomy in ten
      patients. The indications for hysterectomy were uterine rupture (n=12), placenta
      accreta (n=10), uterine atony (n=7), and hemorrhage (n=5). There were two
      maternal deaths, six stillbirths, and two early neonatal deaths. CONCLUSION: This
      study identified surgical deliveries, uterine rupture, placenta accreta, and
      uterine atony as risk factors for emergency peripartum hysterectomy. The most
      common reason for abnormal placental adherence was a previous cesarean section.
      Multiparity and oxytocin use for uterine stimulation were among the risk factors
      for uterine atony that necessitated emergency peripartum hysterectomy.

PMID- 16463167
TI  - Heterotopic pregnancy following ovulation induction by clomiphene citrate and
      timed intercourse: a case report.
AB  - We report a combined intra-uterine and unruptured tubal pregnancy following
      ovulation induction by clomiphene citrate (CC) and timed intercourse. The
      diagnosis of heterotopic pregnancy (HP) is the major problem until occurrence of
      tubal rupture. Because HP is a life-threatening condition, the diagnosis should
      be made as soon as possible. In a spontaneous conception, HP is a rare event. The
      risk of HP significantly increases after ovulation induction. Clomiphene itself
      could be associated with a high HP rate. We present a case with normally
      developing intra-uterine singleton pregnancy successfully managed by
      salpingectomy of synchronous tubal pregnancy following ovulation induction by CC
      and a review of the literature.

PMID- 16463168
TI  - The effects of orchiopexy on serum anti-Mullerian hormone levels in unilateral
      cryptorchid infants.
AB  - BACKGROUND/PURPOSE: In males, serum anti-Mullerian hormone (AMH) reflects Sertoli
      cell function and provides an estimate of seminiferous tubular integrity. It has
      been suggested that comparison of AMH levels before and after surgery could be
      useful to determine effectiveness of the treatment. In this study, we determined
      the serum AMH levels in infants with unilateral cryptorchidism before and after
      orchiopexy procedure and compared these data with the AMH values in age-matched
      controls. METHODS: The study population was 20 cryptorchid children with
      unilateral palpable testes who underwent orchiopexy as a cryptorchid group, and
      20 healthy children who underwent circumcision as a control group. All children
      are 12 months of age. Serum AMH levels were measured at just before surgery (at
      12 month old) and 6 months after surgery (at 18 month old). RESULTS AND
      CONCLUSIONS: All undescended testes were found to be normal in size and in the
      superficial inguinal pouch or subcutaneous region of the groin at surgery. With
      regard to the preoperative serum AMH levels, there was a significant difference
      between the cryptorchid and the control groups (40.04 +/- 4.97 ng/ml versus 53.46
      +/- 7.51 ng/ml) (P < 0.05). Similarly, the postoperative serum AMH levels were
      lower in cryptorchid children than in controls (39.27 +/- 4.58 ng/ml versus 52.79
      +/- 6.27 ng/ml) (P < 0.05). In cryptorchid children, serum AMH levels measured at
      6 months after orchiopexy were similar with preoperative basal levels (40.04 +/-
      4.97 ng/ml versus 39.27 +/- 4.58 ng/ml) (P > 0.05). AMH levels in children with
      unilateral palpable undescended testes remain unchanged 6 months after orchiopexy
      performed at 1 year of age. This is the first report in literature regarding the
      effect of orchiopexy on the serum AMH levels.

PMID- 16463169
TI  - A complete supra-patellar plica with an unusual presentation.
AB  - A suprapatellar plica is a persistent remnant of the embryologic synovial
      membrane between the suprapatellar pouch and the knee joint. Pathologic synovial
      plica is not a common entity, however, when present, it can mimic a variety of
      clinical situations. We describe here a case of pathologic suprapatellar plica
      that has a check-valve mechanism, which results in a clinical presentation as
      knee joint swelling.

PMID- 16463171
TI  - Spatial and temporal patterns of expression of melanocortin type 2 and 5
      receptors in the fetal mouse tissues and organs.
AB  - In the present study to analyze the role of ACTH in fetal tissues and organs, we
      observed the expression of melanocortin type 2 (MC2) and 5 (MC5) receptors in ICR
      mouse embryos from E11.5 to E18.5 by immunohistochemistry. In the adrenal gland
      and testis, both receptors were expressed from E13.5 to E18.5. In the genital
      ridge and the ovary, melanocortin type 2 receptors (MC2R) was detected from E11.5
      to E12.5 and from E13.5 to E18.5, respectively, while melanocortin type 5
      receptors (MC5R) was not detected. In the mesonephros, MC2R and MC5R were
      expressed from E11.5 to E12.5, and in the metanephros, MC2R and MC5R were
      expressed from E12.5 to E18.5 and from E14.5 to E18.5, respectively. In the lung,
      MC2R was expressed from E11.5 to E14.5, but MC5R was not expressed at all. In
      blood cells, MC5R was detected at all stages examined, while MC2R was detected at
      none. MC2R was observed in the brain and spinal cord from E11.5 to E13.5, while
      MC5R was detected only in the telencephalon and only from E16.5 to E18.5. At
      different temporal patterns, MC2R, but not MC5R, was detected in the choroid
      plexus, while MC5R, but not MC2R, was expressed in the liver and in the nasal
      epithelium, and both MC2R and MC5R were expressed in the dorsal root ganglion and
      the trigeminal ganglion. These findings show the spatio-temporal specific
      expression patterns of MC2R and MC5R in the mouse embryo and suggest that ACTH
      may be related to histogenesis and/or prenatal function of various tissues and
      organs via MC2R and/or MC5R.

PMID- 16463170
TI  - Meniscal allograft transplantation: long-term clinical results with radiological
      and magnetic resonance imaging correlations.
AB  - Long-term data on the clinical outcome and the fate of the meniscus allograft
      after transplantation are scarce. In this study we present the clinical,
      radiological and MRI outcome of the meniscus graft and the articular cartilage
      after 42 meniscus allograft transplantations in 41 patients with a minimum follow
      up of 10 years. A total of 27 medial and 15 lateral meniscal allografts were
      transplanted. Eleven of the medial allograft procedures were associated with a
      high tibial osteotomy. The patients were evaluated clinically at the time of
      transplantation and at the final follow-up using the modified HSS scoring system.
      The knee injury and osteoarthritis outcome score (KOOS) was used as an evaluation
      tool for patient-related outcome at the final follow-up. Joint space width
      narrowing and Fairbank changes were radiological outcome parameters, which were
      available for 32 patients. Femoral and tibial cartilage degeneration, graft
      extrusion and signal intensity were scored on MRI scans obtained in 17 patients
      approximately 1 year after transplantation and at the final follow-up (>10
      years). For statistical analysis the patients were divided into three groups:
      lateral meniscal allograft (LMT), medial meniscal allograft transplantation with
      a high tibial osteotomy (MMT+HTO) and without (MMT). The modified HSS score
      revealed a significant improvement in pain and function at the final follow-up
      for all groups. Further analysis also revealed that an MMT+HTO procedure resulted
      in a greater improvement at the final follow-up when compared to MMT.
      Nonetheless, the KOOS scores obtained at the final follow-up revealed the
      presence of substantial disability and symptoms, in addition to a reduced quality
      of life. Radiographical analysis revealed no further joint space narrowing in
      13/32 knees (41%). Fairbank changes remained stable in 9/32 knees (28%). MRI
      analysis showed no progression of cartilage degeneration in 6/17 knees (35%). An
      increased signal intensity of the allograft was present, as was partial graft
      extrusion in the majority of patients at the final follow-up. Seven cases had to
      be converted to a total knee arthroplasty during the follow-up; the overall
      failure rate was 18%. Long-term results after viable meniscus allograft
      transplantation are encouraging in terms of pain relief and improvement of
      function. Despite this significant improvement, substantial disability and
      symptoms were present in all investigated subgroups. Progression of further
      cartilage degeneration or joint space narrowing was absent in a considerable
      number of cases, indicating a potential chondroprotective effect. Level of
      evidence is therapeutic study, Level IV and retrospective analysis of
      prospectively collected data.

PMID- 16463172
TI  - Whole-cell living biosensors--are they ready for environmental application?
AB  - Since the development of the first whole-cell living biosensor or bioreporter
      about 15 years ago, construction and testing of new genetically modified
      microorganisms for environmental sensing and reporting has proceeded at an ever
      increasing rate. One and a half decades appear as a reasonable time span for a
      new technology to reach the maturity needed for application and commercial
      success. It seems, however, that the research into cellular biosensors is still
      mostly in a proof-of-principle or demonstration phase and not close to extensive
      or commercial use outside of academia. In this review, we consider the
      motivations for bioreporter developments and discuss the suitability of extant
      bioreporters for the proposed applications to stimulate complementary research
      and to help researchers to develop realistic objectives. This includes the
      identification of some popular misconceptions about the qualities and
      shortcomings of bioreporters.

PMID- 16463173
TI  - Controlling food-contaminating fungi by targeting their antioxidative stress
      response system with natural phenolic compounds.
AB  - The antioxidative stress-response system is essential to fungi for tolerating
      exposure to phenolic compounds. We show how this system can be targeted to
      improve fungal control by using compounds that inhibit the fungal mitochondrial
      respiratory chain. Targeting mitochondrial superoxide dismutase with selected
      phenolic acid derivatives (e.g., vanillyl acetone) resulted in a 100- to 1,000
      fold greater sensitivity to strobilurin or carboxin fungicides. This synergism is
      significantly greater with strobilurin than with carboxin, suggesting that
      complex III of the mitochondrial respiratory chain is a better target than
      complex II for fungal control, using phenolics. These results show certain
      natural compounds are effective synergists to commercial fungicides and can be
      used for improving control of food-contaminating pathogens. These results suggest
      that the use of such compounds for fungal control can reduce environmental and
      health risks associated with commercial fungicides, lower cost for control, and
      the probability for development of resistance.

PMID- 16463174
TI  - Keystone predators (eastern newts, Notophthalmus viridescens) reduce the impacts
      of an aquatic invasive species.
AB  - Predation, competition, and their interaction are known to be important factors
      that influence the structure of ecological communities. In particular, in those
      cases where a competitive hierarchy exists among prey species, the presence of
      certain keystone predators can result in enhanced diversity in the prey
      community. However, little is known regarding the influence of keystone predator
      presence on invaded prey communities. Given the widespread occurrence of invasive
      species and substantial concern regarding their ecological impacts, studies on
      this topic are needed. In this study I used naturalistic replications of an
      experimental tadpole assemblage to assess the influence of predatory eastern
      newts, Notophthalmus viridescens, on the outcome of interspecific competition
      among native and nonindigenous tadpoles. When newts were absent, the presence of
      the tadpoles of one invasive species, the Cuban treefrog, Osteopilus
      septentrionalis, resulted in decreased survival and growth rate of the dominant
      native species, Bufo terrestris, and dominance of the tadpole assemblage by O.
      septentrionalis. However, the presence of one adult newt generally reduced or
      eliminated the negative impacts of O. septentrionalis tadpoles, resulting in
      comparable survival and performance of native species in invaded and noninvaded
      treatments. Differential mortality among the tadpole species suggests that newts
      preyed selectively on O. septentrionalis tadpoles, supporting the hypothesis that
      newts acted as keystone predators in the invaded assemblage. The presence of
      nonindigenous larval cane toads, Bufo marinus, did not significantly affect
      native species, and this species was not negatively affected by the presence of
      newts. Collectively, these results suggest that eastern newts significantly
      modified the competitive hierarchy of the invaded tadpole assemblage and reduced
      the impacts of a competitively superior invasive species. If general, these
      results suggest that the presence of certain species may be an essential factor
      regulating the ecological impacts of biological invasions.

PMID- 16463175
TI  - Priming of plant defense responses in nature by airborne signaling between
      Artemisia tridentata and Nicotiana attenuata.
AB  - Plants release volatile organic compounds (VOCs) in response to wounding and
      herbivore attack, some of which trigger responses in neighboring unattacked
      plants in the laboratory under conditions that are not likely to occur in the
      real world. Whether plants 'eavesdrop' on the volatile emissions of their
      neighbors in nature is not known. The best documented field study of between
      species signaling via above-ground VOCs involves increases in fitness parameters
      of native tobacco (Nicotiana attenuata) transplanted adjacent to clipped
      sagebrush (Artemesia tridentata tridentata). Clipped sagebrush releases many
      biologically active VOCs, including methyl jasmonate (MeJA), methacrolein and a
      series of terpenoid and green leaf VOCs, of which MeJA, while active under
      laboratory conditions, is not released in sufficient quantities to directly
      elicit induced resistance in the field. Here we demonstrate, with laboratory and
      field-based experiments, that priming (rather than direct elicitation) of native
      N. attenuata's induced chemical defenses by a sagebrush-released VOC bouquet can
      account for earlier findings. With microarrays enriched in N. attenuata herbivore
      regulated genes, we found transcriptional responses in tobacco growing adjacent
      to clipped sagebrush foliage, but failed to detect the direct elicitation of
      defensive chemicals or proteins. However, we observed an accelerated production
      of trypsin proteinase inhibitors when Manduca sexta caterpillars fed on plants
      previously exposed to clipped sagebrush. This readying of a defense response,
      termed priming, results in lower total herbivore damage to plants exposed to
      clipped sagebrush and in a higher mortality rate of young Manduca caterpillars.
      Our study demonstrates priming of plant defense responses as a mechanism of plant
      plant signaling in nature, and provides an example for the analysis of between
      plant signaling under ecologically realistic conditions. Although we describe
      priming as a potential mechanism for signaling between plants in nature, we
      critically discuss the ecological relevance of the particular interaction.

PMID- 16463176
TI  - Linking community and ecosystem development on Mount St. Helens.
AB  - In the two decades following the 1980 eruption of Mount St. Helens in Washington
      State, the N2-fixing colonizer Lupinus lepidus is associated with striking
      heterogeneity in plant community and soil development. We report on differences
      in nutrient availability and plant tissue chemistry between older, dense patches
      (core) of L. lepidus and more recently established low density patches (edge). In
      addition, we conducted a factorial nitrogen and phosphorus fertilization
      experiment in core patches to examine the degree of N and P limitation in early
      primary succession. We found that there were no significant differences in N or P
      availability between core and edge L. lepidus patches during the dry summer
      months, although nutrient availability is very low across the landscape. In the
      high density patches we found lower tissue N content and higher fiber content in
      L. lepidus tissue than in the younger edge patches. The addition of nutrients
      substantially altered plant community composition, with N addition causing an
      increase in other forb biomass and a corresponding competition-induced decline in
      L. lepidus biomass. The majority of the positive biomass response came from
      Hypochaeris radicata. In the second year of the fertilization experiment, the
      addition of N significantly increased total community biomass while L. lepidus
      biomass declined by more than 50%. The response of every species other than L.
      lepidus to N additions suggests that N may be the macronutrient most limiting
      plant production on Mount St. Helens but that the gains in productivity were
      somewhat offset by a decline of the dominant species. By the third year of the
      experiment, L. lepidus began to increase in abundance with P addition. This
      result suggests co-limitation of the community by N and P.

PMID- 16463177
TI  - Mechanism for the small-scale movement of carbon among estuarine habitats:
      organic matter transfer not crab movement.
AB  - In theory, carbon is highly mobile in aquatic systems. Recent evidence from
      carbon stable isotopes of crabs (Parasesarma erythrodactyla and Australoplax
      tridentata), however, shows that in subtropical Australian waters, measurable
      carbon movement between adjacent mangrove and saltmarsh habitats is limited to no
      more than a few metres. We tested whether the pattern in crab delta13C values
      across mangrove and saltmarsh habitats was explained by crab movement, or the
      movement of particulate organic matter. We estimated crab movement in a mark
      recapture program using an array of pitfall traps on 13 transects (a total of 65
      traps) covering an area of 600 m2 across the interface of these two habitats.
      Over a 19-day period, the majority of crabs (91% for P. erythrodactyla, 93% for
      A. tridentata) moved <2 m from the place of initial capture. Crab movement
      cannot, therefore, explain the patterns in delta13C values of crabs. delta13C
      values of detritus collected at 2-m intervals across the same habitat interface
      fitted a sigmoidal curve of a similar form to that fitting the delta13C values of
      crabs. delta13C values of detritus were 2-4 per thousand more depleted in
      saltmarsh (-18.5+/-0.6 per thousand), and 4-7 per thousand more depleted in
      mangroves (-25.9+/-0.1 per thousand) than delta13C values of crabs recorded
      previously in each habitat. Assimilation by crabs of very small detrital
      fragments or microphytobenthos, more enriched in 13C, may explain the disparity
      in delta13C values. Nevertheless, the pattern in delta13C values of detritus
      suggests that crabs obtain their carbon from up to several metres away, but
      without themselves foraging more then a metre or so from their burrow. Such
      detailed measurements of carbon movement in estuaries provide a spatially
      explicit understanding of the functioning of food webs in saltmarsh and mangrove
      habitats.

PMID- 16463178
TI  - Predator defense along a permanence gradient: roles of case structure, behavior,
      and developmental phenology in caddisflies.
AB  - Species replacements along freshwater permanence gradients are well documented,
      but underlying mechanisms are poorly understood for most taxa. In subalpine
      wetlands in Colorado, the relative abundance of caddisfly larvae shifts from
      temporary to permanent basins. Predators on caddisflies also shift along this
      gradient; salamanders (Ambystoma tigrinum nebulosum) in permanent ponds are
      replaced by predaceous diving beetles (Dytiscus dauricus) in temporary habitats.
      We conducted laboratory and field experiments to determine the effectiveness of
      caddisfly cases in reducing vulnerability to these predators. We found that
      larvae of a temporary-habitat caddisfly (Asynarchus nigriculus) were the most
      vulnerable to salamanders. Two relatively invulnerable species (Limnephilus
      externus, L. picturatus) exhibited behaviors that reduced the likelihood of
      detection and attack, whereas the least vulnerable species (Agrypnia deflata) was
      frequently detected and attacked, but rarely captured because cases provided an
      effective refuge. Vulnerability to beetle predation was also affected by cases.
      The stout cases of L. externus larvae frequently deterred beetle larvae, whereas
      the tubular cases of the other species were relatively ineffective. Two of these
      vulnerable species (A. nigriculus and L. picturatus) often co-occur with beetles;
      thus, case construction alone is insufficient to explain patterns of caddisfly
      coexistence along the permanence gradient. One explanation for the coexistence of
      these two species with beetles is that they develop rapidly during early summer
      and pupate before beetle larvae become abundant. One species (L. picturatus)
      pupates by burying into soft substrates that serve as a refuge. The other (A.
      nigriculus) builds stone pupal cases, which in field experiments, more than
      doubles survival compared to organic pupal cases. The combined results of these
      experiments suggest that caddisfly distributions along permanence gradients
      depend on a suite of primary and secondary predator defenses that include larval
      and pupal case structure, predator-specific escape behaviors, and the phenology
      of larval development.

PMID- 16463179
TI  - Fluorescent cationic probes for nuclei of living cells: why are they selective? A
      quantitative structure-activity relations analysis.
AB  - Selectivity of nuclear probes is controlled by competitive accumulation of the
      probe by cellular organelles as well as the high affinity for nucleic acids.
      Physicochemical features of probes which favor nucleic acid binding include
      cationic character and a planar aromatic system above a minimum size. Features of
      probes which permit entry into cells are low protein and lipid binding. Features
      which reduce accumulation in non-nuclear sites include high base strength and
      hydrophilicity of the cation. The overall quantitative structure-activity (QSAR)
      model specifying nuclear accumulation may be expressed as follows: CBN<40; 8>log
      P (neutral species)>0; AI<8; Z>0; -5<log P (cation)<0; pK ( a )>10; LCF>17;
      LCF/CBN>0.70 (where CBN is the conjugated bond number, log P (x )the logarithm of
      the water-octanol partition coefficient of species x, AI the amphilicity index, Z
      the electric charge, pK ( a ) the negative logarithm of the equilibrium constant
      for the free base-protonated base reaction, and LCF the largest conjugated
      fragment). Preliminary applications of the QSAR model--to the selection of
      anticancer drugs, minimization of dye and drug toxicity and the designed
      synthesis of fluorescent probes-are outlined.

PMID- 16463180
TI  - The expression of neurotrophins and their receptors in the prenatal and adult
      human testis: evidence for functions in Leydig cells.
AB  - Previous studies have demonstrated local functions for neurotrophins in the
      developing and mature testis of rodents. To examine whether these signaling
      molecules are present and also potentially active in the human testis, we
      characterized immunohistochemically the expression and cellular localization of
      the known neurotrophins and their receptors during prenatal testicular
      development as well as in the adult human testis. Results obtained revealed the
      presence of nerve growth factor (NGF), brain-derived neurotrophic factor,
      neurotrophin-3 and 4, as well as neurotrophin receptors p75(NTR), TrkA, TrkB, and
      TrkC during testis morphogenesis. These proteins were also detectable in the
      adult human testis, and their local expression could be confirmed largely by
      immunoblot and RT-PCR analyses. Remarkably, the Leydig cells were found to
      represent the predominant neurotrophin/receptor expression sites within both
      fetal and adult human testes. Functional assays performed with a mouse tumor
      Leydig cell line revealed that NGF exposure increases cellular steroid
      production, indicating a role in differentiation processes. These findings
      support previously-recognized neuronal characteristics of Leydig cells, provide
      additional evidence for potential roles of neurotrophins during testis
      morphogenesis and in the mature testis, and demonstrate for the first time a
      neurotrophin-induced functional activity in Leydig cells.

PMID- 16463181
TI  - Meta-analysis of short-term outcomes after laparoscopic resection for rectal
      cancer.
AB  - BACKGROUND: Laparoscopic resection (LR) has become increasingly popular for the
      management of rectal cancer. Despite a decade of experience, the safety and
      efficacy of LR for rectal cancer remains to be established. This report performs
      a meta-analysis to compare LR with conventional open resection (CR) in patients
      with rectal cancer. METHODS: Using a defined search strategy, studies directly
      comparing CR with LR for rectal cancer were identified. The data for patients
      with rectal cancer treated with both approaches were extracted and used in our
      meta-analysis. Open surgery and laparoscopic surgery were compared in terms of
      postoperative mortality, morbidity, complications, oncological clearance,
      operating time, and time before recovery to a normal diet. RESULTS: Compared with
      CR, LR is associated with lower morbidity rates [OR 0.63 (0.41, 1.96) P=0.03],
      longer operating times [weighted mean difference 1.59 (1.20, 1.98) P<0.00001],
      similar mortality rates, wound healing disorder rates, urinary disorder rates,
      cardiopulmony disease rates, all leakage rates, all abscess rates and a positive
      rate of margin. CONCLUSION: LR is associated with less postoperative morbidity,
      but longer operation time. A prospective randomized controlled trial is warranted
      to fully investigate these and other outcome measures.

PMID- 16463182
TI  - The rubrerythrin-like protein Hsp21 of Clostridium acetobutylicum is a general
      stress protein.
AB  - The small heat shock protein Hsp21 of Clostridium acetobutylicum was recently
      identified as a rubrerythrin-like protein with a rubredoxin-like FeS(4) domain at
      the N-terminus and a ferritin-like diiron domain at the C-terminus. Here, we
      report that the two identical tandem genes rbr3A and rbr3B, which encode the heat
      shock protein Hsp21, show the transcription pattern of general stress genes.
      Northern blot analysis indicated that the transcription of the rbr3AB operon is
      induced by various environmental stress conditions: in addition to heat and
      oxidative stress, an increase of the pH of the growth medium from 4.5 to 6.2,
      addition of the salt NaCl (400 mM) or of the solvent butanol (3.5% v/v), and
      lowering the incubation temperature from 37 to 25 degrees C resulted in
      transiently increased transcript levels. The promoter region deduced from the 5'
      end of the mRNA has only limited similarity to the consensus promoter sequence of
      Gram-positive bacteria. A conserved inverted repeat between this promoter and the
      initiation codon is proposed to have a regulatory role. Although C.
      acetobutylicum is regarded as a strictly anaerobic bacterium, live/dead staining
      demonstrated that it can survive exposure to air or H(2)O(2) and other stressors
      to various extents.

PMID- 16463183
TI  - Evolutionary game dynamics in a Wright-Fisher process.
AB  - Evolutionary game dynamics in finite populations can be described by a frequency
      dependent, stochastic Wright-Fisher process. We consider a symmetric game between
      two strategies, A and B. There are discrete generations. In each generation,
      individuals produce offspring proportional to their payoff. The next generation
      is sampled randomly from this pool of offspring. The total population size is
      constant. The resulting Markov process has two absorbing states corresponding to
      homogeneous populations of all A or all B. We quantify frequency dependent
      selection by comparing the absorption probabilities to the corresponding
      probabilities under random drift. We derive conditions for selection to favor one
      strategy or the other by using the concept of total positivity. In the limit of
      weak selection, we obtain the 1/3 law: if A and B are strict Nash equilibria then
      selection favors replacement of B by A, if the unstable equilibrium occurs at a
      frequency of A which is less than 1/3.

PMID- 16463185
TI  - Multiple limit cycles in the standard model of three species competition for
      three essential resources.
AB  - We consider the dynamics of the standard model of 3 species competing for 3
      essential (non-substitutable) resources in a chemostat using Liebig's law of the
      minimum functional response. A subset of these systems which possess cyclic
      symmetry such that its three single-population equilibria are part of a
      heteroclinic cycle bounding the two-dimensional carrying simplex is examined. We
      show that a subcritical Hopf bifurcation from the coexistence equilibrium
      together with a repelling heteroclinic cycle leads to the existence of at least
      two limit cycles enclosing the coexistence equilibrium on the carrying simplex --
      the "inside'' one is an unstable separatrix and the "outside'' one is at least
      semi-stable relative to the carrying simplex. Numerical simulations suggest that
      there are exactly two limit cycles and that almost every positive solution
      approaches either the stable limit cycle or the stable coexistence equilibrium,
      depending on initial conditions. Bifurcation diagrams confirm this picture and
      show additional features. In an alternative scenario, we show that the
      subcritical Hopf together with an attracting heteroclinic cycle leads to an
      unstable periodic orbit separatrix.

PMID- 16463184
TI  - A finite locus effect diffusion model for the evolution of a quantitative trait.
AB  - A diffusion model is constructed for the joint distribution of absolute locus
      effect sizes and allele frequencies for loci contributing to an additive
      quantitative trait under selection in a haploid, panmictic population. The model
      is designed to approximate a discrete model exactly in the limit as both
      population size and the number of loci affecting the trait tend to infinity. For
      the case when all loci have the same absolute effect size, formal multiple
      timescale asymptotics are used to predict the long-time response of the
      population trait mean to selection. For the case where loci can take on either of
      two distinct effect sizes, not necessarily with equal probability, numerical
      solutions of the system indicate that response to selection of a quantitative
      trait is insensitive to the variability of the distribution of effect sizes when
      mutation is negligible.

PMID- 16463186
TI  - Mum, why do you keep on growing? Impacts of environmental variability on optimal
      growth and reproduction allocation strategies of annual plants.
AB  - In their 1990 paper Optimal reproductive efforts and the timing of reproduction
      of annual plants in randomly varying environments, Amir and Cohen considered
      stochastic environments consisting of i.i.d. sequences in an optimal allocation
      discrete-time model. We suppose here that the sequence of environmental factors
      is more generally described by a Markov chain. Moreover, we discuss the
      connection between the time interval of the discrete-time dynamic model and the
      ability of the plant to rebuild completely its vegetative body (from reserves).
      We formulate a stochastic optimization problem covering the so-called linear and
      logarithmic fitness (corresponding to variation within and between years), which
      yields optimal strategies. For "linear maximizers'', we analyse how optimal
      strategies depend upon the environmental variability type: constant, random
      stationary, random i.i.d., random monotonous. We provide general patterns in
      terms of targets and thresholds, including both determinate and indeterminate
      growth. We also provide a partial result on the comparison between ;"linear
      maximizers'' and "log maximizers''. Numerical simulations are provided, allowing
      to give a hint at the effect of different mathematical assumptions.

PMID- 16463187
TI  - Phylogenetic networks from multi-labelled trees.
AB  - It is now quite well accepted that the evolutionary past of certain species is
      better represented by phylogenetic networks as opposed to trees. For example,
      polyploids are typically thought to have resulted through hybridization and
      duplication, processes that are probably not best represented as bifurcating
      speciation events. Based on the knowledge of a multi-labelled tree relating
      collection of polyploids, we present a canonical construction of a phylogenetic
      network that exhibits the tree. In addition, we prove that the resulting network
      is in some well-defined sense a minimal network having this property.

PMID- 16463188
TI  - Mathematical modelling of engineered tissue growth using a multiphase porous flow
      mixture theory.
AB  - This paper outlines the framework of a porous flow mixture theory for the
      mathematical modelling of in vitro tissue growth, and gives an application of
      this theory to an aspect of tissue engineering. The problem is formulated as a
      set of partial differential equations governing the space and time dependence of
      the amounts of each component of the tissue (phase), together with the physical
      stresses in each component. The theory requires constitutive relations to specify
      the material properties of each phase, and also requires relations to specify the
      stresses developed due to mechanical interactions, both within each phase and
      between different phases. An application of the theory is given to the study of
      the mobility and aggregation of a population of cells seeded into an artificial
      polymeric scaffold. Stability analysis techniques show that the interplay of the
      forces between the tissue constituents results in two different regimes: either
      the cells form aggregates or disperse through the scaffold.

PMID- 16463189
TI  - A mathematical investigation of a Clock and Wavefront model for somitogenesis.
AB  - Somites are transient blocks of cells that form sequentially along the antero
      posterior axis of vertebrate embryos. They give rise to the vertebrae, ribs and
      other associated features of the trunk. In this work we develop and analyse a
      mathematical formulation of a version of the Clock and Wavefront model for somite
      formation, where the clock controls when the boundaries of the somites form and
      the wavefront determines where they form. Our analysis indicates that this
      interaction between a segmentation clock and a wavefront can explain the periodic
      pattern of somites observed in normal embryos. We can also show that a
      simplification of the model provides a mechanism for predicting the anomalies
      resulting from perturbation of the wavefront.

PMID- 16463190
TI  - Analysing grouping of nucleotides in DNA sequences using lumped processes
      constructed from Markov chains.
AB  - The most commonly used models for analysing local dependencies in DNA sequences
      are (high-order) Markov chains. Incorporating knowledge relative to the possible
      grouping of the nucleotides enables to define dedicated sub-classes of Markov
      chains. The problem of formulating lumpability hypotheses for a Markov chain is
      therefore addressed. In the classical approach to lumpability, this problem can
      be formulated as the determination of an appropriate state space (smaller than
      the original state space) such that the lumped chain defined on this state space
      retains the Markov property. We propose a different perspective on lumpability
      where the state space is fixed and the partitioning of this state space is
      represented by a one-to-many probabilistic function within a two-level stochastic
      process. Three nested classes of lumped processes can be defined in this way as
      sub-classes of first-order Markov chains. These lumped processes enable
      parsimonious reparameterizations of Markov chains that help to reveal relevant
      partitions of the state space. Characterizations of the lumped processes on the
      original transition probability matrix are derived. Different model selection
      methods relying either on hypothesis testing or on penalized log-likelihood
      criteria are presented as well as extensions to lumped processes constructed from
      high-order Markov chains. The relevance of the proposed approach to lumpability
      is illustrated by the analysis of DNA sequences. In particular, the use of lumped
      processes enables to highlight differences between intronic sequences and gene
      untranslated region sequences.

PMID- 16463191
TI  - Hemispherectomy: a schematic review of the current techniques.
AB  - Anatomical hemispherectomy has been used for the treatment of seizures since
      1938. However, it was almost abandoned in the 1960s after reports of
      postoperative fatalities caused by hydrocephalus, hemosiderosis, and trivial head
      traumas. Despite serious complications, the remarkable improvement of patients
      encouraged authors to carry out modifications on anatomical hemispherectomy in
      order to lessen its morbidity while preserving its efficacy. The effort to
      improve the technique generated several original procedures. This paper reviews
      current techniques of hemispherectomy and proposes a classification scheme based
      on their surgical characteristics. Techniques of hemispherectomy were sorted into
      two major groups: (1) those that remove completely the cortex from the hemisphere
      and (2) those that associate partial cortical removal and disconnection. Group 1
      was subdivided into two subgroups based on the integrity of the ventricular
      cavity and group 2 was subdivided into three subgroups depending on the amount
      and location of the corticectomy. Grouping similar techniques may allow a better
      understanding of the distinctive features of each one and creates the possibility
      of comparing data from different authors.

PMID- 16463192
TI  - Evaluation of the McPeek postoperative outcome score in three trials.
AB  - BACKGROUND: Postoperative outcome of patients is determined by recovery
      characteristics and self-reported quality of life. The first can be assessed with
      the McPeek score which values three aspects of recovery: mortality, postoperative
      critical care and duration of hospitalization. MATERIALS AND METHODS: We
      calculated the McPeek score of 669 patients in three trials: (1) colorectal
      cancer surgery, (2) antihistamine/volume loading in various operations, and (3)
      cholecystectomy. Beforehand, the average of intensive care unit treatment and
      duration of hospitalization were determined for the different operations to
      define McPeek score points. The score was tested on reliability, validity, and
      sensitivity. In addition, clinical applicability was assessed in a survey.
      RESULTS: The score was reliable with similarly distributed score points in the
      three trials at different institutions. Inter-rater reliability was high (97%
      overlap). Validity was proven by moderate high correlation to convergent criteria
      such as complications (trial I to III r=0.43, r=0.38, r=0.60), preoperative
      American Society of Anesthesiologists class (ASA) (r=0.24, r=0.28, r=0.57), and
      age (r=0.23, r=0.32, r=0.31). The score was different between patients with and
      without neoplasms (P<0.001, trial II) and between elective or emergency patients
      (P<0.001, trial III). In a survey, investigators reported that the score was easy
      to assess and more comprehensive than four other scores. CONCLUSIONS: The McPeek
      score values the postoperative outcome on a nonlinear scale. A priori, the
      average duration of hospitalization and critical care for a specific operation
      has to be defined. Our validation suggests that it is a reliable, valid,
      sensitive, and practical instrument for outcome analysis after anesthesia and
      surgery.

PMID- 16463193
TI  - Nicotine psychopharmacology research: advancing science, public health, and
      global policy.

PMID- 16463194
TI  - Nicotine psychobiology: how chronic-dose prospective studies can illuminate some
      of the theoretical issues from acute-dose research.
AB  - RATIONALE: To illustrate how prospective cigarette smoking research can
      illuminate some of the theoretical dilemmas about nicotine psychobiology from
      acute dose research. METHODS AND RESULTS: When briefly deprived smokers are
      administered nicotine, they display a range of psychobiological 'gains', with
      improved cognitive performance, feelings of contentment, and reduced feelings of
      stress or depression. However, abstinence leads to decrements in all these
      functions. The balance between the deficits of nicotine deprivation and the gains
      of reinstatement has been debated for decades. Yet, it still remains
      controversial whether nicotine is psychobiologically beneficial, neutral or
      detrimental. Some illumination may be provided by prospective research. Taking up
      smoking during adolescence is often followed by increased feelings of stress and
      depression, whereas quitting is often associated with subsequent mood gains.
      Short-term prospective studies reveal that the essence of nicotine dependency is
      repetitive psychobiological vascillation. The mood gains of smoke inhalation
      represent the temporary reversal of abstinence effects, and the frequent
      experience of negative states in between cigarettes explains why smoking can
      increase psychobiological distress. This may also be linked with Diathesis-Stress
      models. If withdrawal symptoms reflect the exacerbation of natural
      predispositions, then 'disadvantaged' smokers will suffer the worst abstinence
      symptoms and develop the strongest nicotine dependency. This explanation
      contrasts with the self-medication model, which focuses on the immediate benefits
      of smoke inhalation, rather than the overall costs of nicotine use. CONCLUSIONS:
      The frequent experience of negative psychological states in between cigarettes
      helps to explain why nicotine dependency is associated with a range of
      psychobiological problems.

PMID- 16463196
TI  - Use of a patient information leaflet to influence patient decisions regarding
      mode of administration of NSAID medications in case of acute low back pain.
AB  - Despite dissuasive recommendations, intramuscular (i.m.) injections of NSAIDS are
      still a widespread treatment of acute pain in General Practice as well as among
      orthopaedic physicians. Most physicians argue that patients who are used to
      receive NSAIDS i.m. would insist on this application mode while being convinced
      of its therapeutic superiority for pain relief. Therefore, the aim of the study
      was to find out if patients' decision can be influenced towards an oral
      application by receiving a simple information leaflet. An information leaflet,
      providing information about the risks of NSAIDS particularly in case of i.m.
      application was provided to 161 patients with acute low back pain. Decision in
      favour or against i.m. application of NSAIDS was documented. Severity of disease
      was assessed by the Roland Morrison pain questionnaire and visual analogue scale
      (VAS) at the first visit and again 3-5 days later. From May to December 2004, 161
      patients, visiting their GP (13 practices) with acute pain and demanding an
      injection were included in the study. After reading the information leaflet, 139
      of the 161 (86.3%) patients decided for an oral application instead of receiving
      an injection of NSAIDS as in the past. This effect was statistically significant
      (P</=0.01). Of the initial 161 patients, 156 could be re-evaluated and no
      significant differences in the VAS and the Roland Morris Score between the
      patients with oral and i.m. application mode could be found. Only 2 patients of
      the 139 who decided for oral application indicated that they would opt for an
      i.m. injection next time. Our study demonstrates that patients' decision can be
      influenced even in case of severe pain by providing adequate information on a
      short information leaflet. The results should help to reduce physicians' fear of
      losing patients when not following their demand for i.m. injections and therefore
      enable a safer pain treatment.

PMID- 16463195
TI  - Direct repair for treatment of symptomatic spondylolysis and low-grade isthmic
      spondylolisthesis in young patients: no benefit in comparison to segmental fusion
      after a mean follow-up of 14.8 years.
AB  - The aim of the present study was to assess the long-term clinical, functional,
      and radiographic outcome of direct repair of spondylolysis using cerclage wire
      fixation according to Scott in young patients with symptomatic spondylolysis or
      low-grade isthmic spondylolisthesis as compared to the outcome after
      uninstrumented posterolateral in situ fusion. Twenty-five out of 28 patients of
      the direct repair group (89%) and 23 out of 28 of the fusion group (82%) were
      available for follow-up examination. The assessment by independent observers
      included a structured interview (Oswestry questionnaire [ODI], visual analogue
      scale, SRS questionnaire), a clinical examination, functional testing, plain
      radiography, and MRI. The groups were comparable as to the mean age at operation
      (18.2 vs. 16.2 years.), the follow-up time (14.8 vs. 15.0 years), and the amount
      of preoperative slip (7.2 vs. 13.1%). The mean ODI and SRS total scores were
      significantly better in the fusion group (4.3 [0-16] and 96 [57-117]) as compared
      to the direct repair group (11.4[0-52] and 87[53-107]; P=0.02 and P=0.011,
      respectively). In functional testing, both groups reached normal values for
      abdominal and back muscle strength. The lumbar spine flexion and extension ROM
      was decreased in both groups showing no statistical difference between the
      groups. Significant progressive narrowing of the olisthetic disc was detected on
      the plain radiographs after direct repair. On the flexion-extension radiographs,
      in the direct repair group, the mobility in the lytic/olisthetic segment was
      decreased in comparison to normal values from the literature. The mobility at the
      level above the operated segment was decreased in the direct repair group as
      compared to the fusion group (P=0.057). On T2-weighted MR images in the direct
      repair group, the signal intensity of the disc below the affected vertebra was
      decreased in 17/23 (74%) patients. There was no difference between the groups in
      the nucleus signal intensity of the adjacent disc above the operated segment. No
      association between the disc degeneration on MRI and the outcome of the patients
      could be established. In the direct repair group the following complications were
      seen: transient nerve root irritation (2), superficial infection (1), UTI (1); in
      the fusion group the complications were: subcutaneous seroma (2) and UTI (1).
      There were six re-operations, cerclage removal(4), conversion into segmental
      fusion(2) in the direct repair group, and one re-operation, instrumented
      respondylodesis, in the fusion group. In conclusion, the results of direct repair
      of the spondylolysis using cerclage wire fixation according to Scott were very
      satisfactory in 76% of the patients after a mean follow-up of 14.8 years. After
      direct repair, the ODI deteriorated with time leading to a clinically moderate
      but statistically significant difference in favour of segmental fusion. Lumbar
      spine mobility was decreased after direct repair. Secondary segmental instability
      above the spinal fusion was not detected. The procedure does not seem to be
      capable of preventing the olisthetic disc from degeneration. The theoretical
      benefits of direct repair could not be proven.

PMID- 16463197
TI  - Long-term randomised comparison between a carbon fibre cage and the Cloward
      procedure in the cervical spine.
AB  - A prospective randomised study. To compare the long-term outcome of anterior
      cervical decompression and fusion (ACDF) with a cervical intervertebral fusion
      cage (CIFC) and the Cloward procedure (CP). We have previously shown that the 2
      year outcome of ACDF with the CIFC is the same as for the CP. The fusion rate in
      CIFC group was, however, only 55%, compared to 85% in CP group. The long-term
      outcome of CIFC is poorly documented. Ninety-five patients with at least 6 months
      duration of neck pain and radicular arm pain were randomly allocated for ACDF
      with the CIFC or the CP. Radiographs were obtained at 2 years. Questionnaires
      about pain, disability (Neck Disability Index, NDI), distress, quality of life
      and global outcome were obtained from 83 patients (87%) (43 CIFC, 40 CP) at a
      mean follow-up time of 6 years (range 56-94 months). There were no significant
      differences in any outcome variable between the two treatments. For both CP and
      CIFC the pain intensity improved (P<0.0001) whereas the NDI was unchanged at long
      term follow-up compared to preoperatively. In the CIFC group patients with a
      healed fusion had significantly less mean pain (24 mm) and NDI (26%) than
      patients with pseudarthrosis (42 and 41, respectively). Furthermore, the mean
      pain and NDI reported by CIFC patients with a healed fusion was significantly
      less than in healed CP patients (37 and 38, respectively). The long-term outcome
      is the same for the CIFC and the CP, with similar improvements of pain but with
      considerable remaining functional disability. However, in the subgroup of
      patients with healed CIFC the outcome was clearly better than for the non-healed
      CIFC group, and also clearly better than for the healed CP group. Thus, if the
      healing problem associated with the CIFC can be solved the results indicate that
      a better outcome can be expected with the cage than with the CP.

PMID- 16463199
TI  - Misleading history of pain location in 51 patients with osteoporotic vertebral
      fractures.
AB  - The aim of this study was to investigate associations between the location of
      osteoporotic vertebral fractures and the patient's localization of pain. Fifty
      one consecutive patients (m 6, f 45; average age 74.8 years) with diagnosed
      osteoporotic vertebral fractures between T8 and L2 were included in the study.
      Exclusion criteria were fractures above T8 and below L2, spondylolisthesis, disc
      herniations, tumors, infections, and instability. Pain location was assessed by
      pain drawing, subdivided into thoracic, lumbar, and thoracic plus lumbar pain
      areas, and pain intensity using a 101 numeric rating scale. Furthermore, the
      onset of back pain and the lack or the indication of a trigger event at the onset
      of pain were documented. Only four of 20 patients with thoracic fractures
      reported thoracic pain, while the other 16 (80%) reported only lumbar pain. The
      location of the fracture and the patient's pain report were not related (Cohens
      Kappa=0.046; P=0.438). Patients with thoracic or lumbar osteoporotic fractures
      report pain mainly in the lumbosacrogluteal area. Therefore, the complaint of low
      back pain (LBP) in persons at risk for osteoporotic fractures may require both
      thoracic and lumbar X-rays. LBP patients with a suspect history of an
      osteoporotic vertebral fracture should also be given an X-ray of the thoracic and
      lumbar spine. Patients with a thoracic vertebral fracture had more severe pain
      than patients with a lumbar vertebral fracture. Onset not related to a fall or a
      false movement related to a significantly longer pain duration.

PMID- 16463198
TI  - Cost and utilization of blood transfusion associated with spinal surgeries in the
      United States.
AB  - The purpose of this study was to examine factors associated with the utilization
      and cost of blood transfusion during and post-spinal fusion surgery. A
      retrospective, observational study of 42,029 inpatients undergoing spinal fusion
      surgery in United States hospitals participating in the Perspective( Comparative
      Database for inpatient use was conducted. Descriptive analysis, logistic
      regression, and ordinary least squares (OLS) regression were used to describe the
      factors associated with the use and cost of allogeneic blood transfusion (ABT).
      Hospitalization costs were $18,690 (SD=14,159) per patient, erythropoietin costs
      were $85.25 (SD=3,691.66) per patient, and topical sealant costs were $414.34
      (SD=1,020.06) per patient. Sub-analysis of ABT restricted to users revealed ABT
      costs ranged from $312.24 (SD=543.35) per patient with whole blood to $2,520
      (SD=3,033.49) per patient with fresh frozen plasma. Patients that received
      hypotensive anesthesia (OR,1.61; 95% CI, 1.47-1.77), a volume expander (OR,1.95;
      95% CI, 1.75-2.18), autologous blood (OR, 2.04; 95% CI, 1.71-2.42), or an
      erythropoietic agent (OR=1.64; 95% CI, 1.27-2.12) had a higher risk of ABT.
      Patients that received cell salvage had a lower risk of transfusion (OR=0.40; 95%
      CI, 0.32-0.50). Most blood avoidance techniques have low utilization or do not
      reduce the burden of transfusion associated with spinal fusion.

PMID- 16463200
TI  - The interobserver-validated relevance of intervertebral spacer materials in MRI
      artifacting.
AB  - Intervertebral spacers for anterior spine fusion are made of different materials,
      such as titanium, carbon or cobalt-chrome, which can affect the post-fusion MRI
      scans. Implant-related susceptibility artifacts can decrease the quality of MRI
      scans, thwarting proper evaluation. This cadaver study aimed to demonstrate the
      extent that implant-related MRI artifacting affects the post-fusion evaluation of
      intervertebral spacers. In a cadaveric porcine spine, we evaluated the post
      implantation MRI scans of three intervertebral spacers that differed in shape,
      material, surface qualities and implantation technique. A spacer made of human
      cortical bone was used as a control. The median sagittal MRI slice was divided
      into 12 regions of interest (ROI). No significant differences were found on 15
      different MRI sequences read independently by an interobserver-validated team of
      specialists (P>0.05). Artifact-affected image quality was rated on a score of 0-1
      2. A maximum score of 24 points (100%) was possible. Turbo spin echo sequences
      produced the best scores for all spacers and the control. Only the control
      achieved a score of 100%. The carbon, titanium and cobalt-chrome spacers scored
      83.3, 62.5 and 50%, respectively. Our scoring system allowed us to create an
      implant-related ranking of MRI scan quality in reference to the control that was
      independent of artifact dimensions. The carbon spacer had the lowest percentage
      of susceptibility artifacts. Even with turbo spin echo sequences, the
      susceptibility artifacts produced by the metallic spacers showed a high degree of
      variability. Despite optimum sequencing, implant design and material are relevant
      factors in MRI artifacting.

PMID- 16463201
TI  - Fabry disease: an ultrastructural comparative study of skin in hemizygous and
      heterozygous patients.
AB  - Fabry disease is a rare X-linked lysosomal storage disorder due to alpha
      galactosidase A deficiency, better known after the advent of a promising
      treatment, a periodical enzyme replacement. As other hereditary X-linked
      disorders, females have historically been considered non-affected carriers,
      although they are, actually, clinically and pathologically affected to a variable
      degree. Some women are asymptomatic, but the majority present milder forms of the
      disease and later onset. This wide range of disease expression is supposed to be
      related to the levels of enzymatic activity, probably in accordance with a
      skewing of X inactivation. Lysosomal deposits of ceramide trihexoside have been
      repeatedly documented in a wide range of tissues, including those found in
      angiokeratoma, the characteristic cutaneous lesion which allowed the definition
      of Fabry disease. The aim of this study was to investigate whether there was any
      difference in the amount of dermal lysosomal storage in males and females, thus
      accounting for the difference in clinical severity of both groups. For that
      purpose, with electron microscopy and quantitative methods, we studied the extent
      of lysosomal deposits in dermal fibroblasts of normal-appearing skin in six
      females and nine men, enzymatically and genetically proven as to have Fabry
      disease, and results were compared. Our results indicate a statistically
      significant difference between the two groups regarding both the percentage of
      dermal fibroblasts bearing stored material, and the storage surface occupied in
      100 fibroblasts per case. We suggest that periodical ultrastructural examination
      of normal-appearing skin could be an indicator of the efficacy of enzyme
      replacement therapy and could help to evaluate results.

PMID- 16463202
TI  - Rare mutation of PIK3CA in meningiomas.

PMID- 16463203
TI  - Identification of sugar-modulated genes and evidence for in vivo sugar sensing in
      Arabidopsis.
AB  - Sugar status regulates mechanisms controlling growth and development of plants.
      We studied the effects of sucrose at a genome-wide level in dark-grown 4-day-old
      Arabidopsis thaliana seedlings, identifying 797 genes strongly responsive to
      sucrose. Starting from the microarray analysis data, four up-regulated
      (At5g41670, At1g20950, At1g61800, and At2g28900) and four down-regulated (DIN6,
      At4g37220, At1g28330, and At1g74670) genes were chosen for further
      characterisation and as sugar sensing markers for in vivo analysis. The sugar
      modulation pattern of all eight genes was confirmed by real time RT-PCR analysis,
      revealing different concentration thresholds for sugar modulation. Finally, sugar
      regulation of gene expression was demonstrated in vivo by using the starchless
      pgm mutant, which is unable to produce transitory starch. Sucrose-inducible genes
      are upregulated in pgm leaves at the end of a light treatment, when soluble
      sugars levels are higher than in the wild type. Conversely, sucrose-repressible
      genes show a higher expression at the end of the dark period in the mutant, when
      the levels of sugars in the leaf are lower. The results obtained indicate that
      the transcriptional response to exogenous sucrose allows the identification of
      genes displaying a pattern of expression in leaves compatible with their sugar
      modulation in vivo.

PMID- 16463205
TI  - JPN Guidelines for the management of acute pancreatitis: cutting-edge
      information.
AB  - The JPN Guidelines for the Management of Acute Pancreatitis are organized under
      the subject headings: epidemiology, diagnosis, management strategy, severity
      assessment and transfer criteria, management of gallstone pancreatitis,
      nonsurgical management, and surgical management. The Guidelines contain cutting
      edge information on each of these subjects, as well as a section on the Japanese
      medical insurance system which provides information that should prove useful to
      physicians in other countries. The quality of the evidence was evaluated by the
      evidence-based classification method used at the Cochrane Library. The levels of
      recommendation of the individual management methods contained in the Guidelines
      were determined on the basis of the evaluation of evidence by the consensus of
      the members of the Working Group (see below). The Japanese Society for Abdominal
      Emergency Medicine, the Japan Pancreas Society, and the Research Group for
      Intractable Diseases and Refractory Pancreatic Diseases (which is sponsored by
      the Japanese Ministry of Health, Labour, and Welfare) were commissioned to
      produce the JPN Guidelines for the Management of Acute Pancreatitis. A Working
      Group of 20 physicians specializing in pancreatic diseases and emergency medicine
      investigated and analyzed 14821 cases retrieved by means of a Medline (1960-2004)
      search and discussed the available literature on acute pancreatitis (limited to
      human pancreatitis). The Working Group held many general discussions in order to
      reach a consensus on the content of the Guidelines. After producing a draft, the
      Publishing Committee of the JPN Guidelines for the Management of Acute
      Pancreatitis posted it on a website and asked for comments and criticisms.
      Subsequently, a final version of the Guidelines was published in Japanese in
      2003. The Publishing Committee is now making the Guidelines available to a much
      wider readership by bringing out an English version.

PMID- 16463206
TI  - Health insurance system and payments provided to patients for the management of
      severe acute pancreatitis in Japan.
AB  - The health insurance system in Japan is based upon the Universal Medical Care
      Insurance System, which gives all citizens the right to join an insurance scheme
      of their own choice, as guaranteed by the provisions of Article 25 of the
      Constitution of Japan, which states: "All people shall have the right to maintain
      the minimum standards of wholesome and cultured living." The health care system
      in Japan includes national medical insurance, nursing care for the elderly, and
      government payments for the treatment of intractable diseases. Medical insurance
      provisions are handled by Employee's Health Insurance (Social Insurance), which
      mainly covers employees of private companies and their families, and by National
      Health Insurance, which provides for the needs of self-employed people. Both
      schemes have their own medical care service programs for retired persons and
      their families. The health care system for the elderly covers people 75 years of
      age and over and bedridden people 65 years of age and over. There is also a
      system under which the government pays all or part of medical expenses, and/or
      pays medical expenses not covered by insurance. This is referred to collectively
      as the "medical expenses payment system" and includes the provision of medical
      assistance for specified intractable diseases. Because severe acute pancreatitis
      has a high mortality rate, it is specified as an intractable disease. In order to
      lower the mortality rate of various diseases, including severe acute
      pancreatitis, the specification system has been adopted by the government. The
      cost of treatment for severe acute pancreatitis is paid in full by the government
      from the date the application is made for a certificate verifying that the
      patient has an intractable disease.

PMID- 16463208
TI  - JPN Guidelines for the management of acute pancreatitis: diagnostic criteria for
      acute pancreatitis.
AB  - The currently used diagnostic criteria for acute pancreatitis in Japan are
      presentation with at least two of the following three manifestations: (1) acute
      abdominal pain and tenderness in the upper abdomen; (2) elevated levels of
      pancreatic enzyme in the blood, urine, or ascitic fluid; and (3) abnormal imaging
      findings in the pancreas associated with acute pancreatitis. When a diagnosis is
      made on this basis, other pancreatic diseases and acute abdomen can be ruled out.
      The purpose of this article is to review the conventional criteria and, in
      particular, the various methods of diagnosis based on pancreatic enzyme values,
      with the aim of improving the quality of diagnosis of acute pancreatitis and
      formulating common internationally agreed criteria. The review considers the
      following recommendations: Better even than the total blood amylase level, the
      blood lipase level is the best pancreatic enzyme for the diagnosis of acute
      pancreatitis and its differentiation from other diseases. A pivotal factor in the
      diagnosis of acute pancreatitis is identifying an increase in pancreatic enzymes
      in the blood. Ultrasonography (US) is also one of the procedures that should be
      performed in all patients with suspected acute pancreatitis. Magnetic resonance
      imaging (MRI) is one of the most important imaging procedures for diagnosing
      acute pancreatitis and its intraperitoneal complications. Computed tomography
      (CT) is also one of the most important imaging procedures for diagnosing acute
      pancreatitis and its intraabdominal complications. CT should be performed when a
      diagnosis of acute pancreatitis cannot be established on the basis of the
      clinical findings, results of blood and urine tests, or US, or when the etiology
      of the pancreatitis is unknown. When acute pancreatitis is suspected, chest and
      abdominal X-ray examinations should be performed to determine whether any
      abnormal findings caused by acute pancreatitis are present. Because the etiology
      of acute pancreatitis can have a crucial influence on both the treatment policy
      and severity assessment, it should be evaluated promptly and accurately. It is
      particularly important to differentiate between gallstone-induced acute
      pancreatitis, which requires treatment of the biliary system, and alcohol-induced
      acute pancreatitis, which requires a different form of treatment.

PMID- 16463209
TI  - JPN Guidelines for the management of acute pancreatitis: severity assessment of
      acute pancreatitis.
AB  - This article addresses the criteria for severity assessment and the severity
      scoring system of the Ministry of Health and Welfare of Japan; now the Japanese
      Ministry of Health, Labour, and Welfare (the JPN score). It also presents data
      comparing the JPN score with the Acute Physiology and Chronic Health Evaluation
      (APACHE) II score and the Ranson score, which are the major measuring scales used
      in the United States and Europe. The goal of investigating these scoring systems
      is the achievement of earlier diagnosis and more appropriate and successful
      treatment of severe or moderate acute pancreatitis, which has a high mortality
      rate. This article makes the following recommendations in terms of assessing the
      severity of acute pancreatitis: (1) Severity assessment is indispensable to the
      selection of proper initial treatment in the management of acute pancreatitis
      (Recommendation A). (2) Assessment by a severity scoring system (JPN score,
      APACHE II score) is important for determining treatment policy and identifying
      the need for transfer to a specialist unit (Recommendation A). (3) C-reactive
      protein (CRP) is a useful indicator for assessing severity (Recommendation A).
      (4) Contrast-enhanced computed tomography (CT) scanning and contrast-enhanced
      magnetic resonance imaging (MRI) play an important role in severity assessment
      (Recommendation A). (5) A JPN score of 2 or more (severe acute pancreatitis) has
      been established as the criterion for hospital transfer (Recommendation A). (6)
      It is preferable to transfer patients with severe acute pancreatitis to a
      specialist medical institution where they can receive continuous monitoring and
      systemic management.

PMID- 16463207
TI  - JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology,
      natural history, and outcome predictors in acute pancreatitis.
AB  - Acute pancreatitis is a common disease with an annual incidence of between 5 and
      80 people per 100,000 of the population. The two major etiological factors
      responsible for acute pancreatitis are alcohol and cholelithiasis (gallstones).
      The proportion of patients with pancreatitis caused by alcohol or gallstones
      varies markedly in different countries and regions. The incidence of acute
      alcoholic pancreatitis is considered to be associated with high alcohol
      consumption. Although the incidence of alcoholic pancreatitis is much higher in
      men than in women, there is no difference in sexes in the risk involved after
      adjusting for alcohol intake. Other risk factors include endoscopic retrograde
      cholangiopancreatography, surgery, therapeutic drugs, HIV infection,
      hyperlipidemia, and biliary tract anomalies. Idiopathic acute pancreatitis is
      defined as acute pancreatitis in which the etiological factor cannot be
      specified. However, several studies have suggested that this entity includes
      cases caused by other specific disorders such as microlithiasis. Acute
      pancreatitis is a potentially fatal disease with an overall mortality of 2.1%
      7.8%. The outcome of acute pancreatitis is determined by two factors that reflect
      the severity of the illness: organ failure and pancreatic necrosis. About half of
      the deaths in patients with acute pancreatitis occur within the first 1-2 weeks
      and are mainly attributable to multiple organ dysfunction syndrome (MODS).
      Depending on patient selection, necrotizing pancreatitis develops in
      approximately 10%-20% of patients and the mortality is high, ranging from 14% to
      25% of these patients. Infected pancreatic necrosis develops in 30%-40% of
      patients with necrotizing pancreatitis and the incidence of MODS in such patients
      is high. The recurrence rate of acute pancreatitis is relatively high: almost
      half the patients with acute alcoholic pancreatitis experience a recurrence. When
      the gallstones are not treated, the risk of recurrence in gallstone pancreatitis
      ranges from 32% to 61%. After recovering from acute pancreatitis, about one-third
      to one-half of acute pancreatitis patients develop functional disorders, such as
      diabetes mellitus and fatty stool; the incidence of chronic pancreatitis after
      acute pancreatitis ranges from 3% to 13%. Nevertheless, many reports have shown
      that most patients who recover from acute pancreatitis regain good general health
      and return to their usual daily routine. Some authors have emphasized that
      endocrine function disorders are a common complication after severe acute
      pancreatitis has been treated by pancreatic resection.

PMID- 16463212
TI  - JPN Guidelines for the management of acute pancreatitis: treatment of gallstone
      induced acute pancreatitis.
AB  - Gallstones, along with alcohol, are one of the primary etiological factors of
      acute pancreatitis, and knowledge of the etiology as well as the diagnosis and
      management of gallstones, is crucial for managing acute pancreatitis. Because of
      this, evidence regarding the management of gallstone-induced pancreatitis in
      Japan was collected, and recommendation levels were established by comparing
      current clinical practices with optimal clinical practices. The JPN Guidelines
      for managing gallstone-induced acute pancreatitis recommend two procedures: (1)
      an urgent endoscopic procedure should be performed in patients in whom biliary
      duct obstruction is suspected and in patients complicated by cholangitis
      (Recommendation A); and (2) after the attack of gallstone pancreatitis has
      subsided, a laparoscopic cholecystectomy should be performed during the same
      hospital stay (Recommendation B).

PMID- 16463210
TI  - JPN Guidelines for the management of acute pancreatitis: medical management of
      acute pancreatitis.
AB  - The basic principles of the initial management of acute pancreatitis are adequate
      monitoring of vital signs, fluid replacement, correction of any electrolyte
      imbalance, nutritional support, and the prevention of local and systemic
      complications. Patients with severe acute pancreatitis should be transferred to a
      medical facility where adequate monitoring and intensive medical care are
      available. Strict cardiovascular and respiratory monitoring is mandatory for
      maintaining the cardiopulmonary system in patients with severe acute
      pancreatitis. Maximum fluid replacement is needed to stabilize the cardiovascular
      system. Prophylactic antibiotic administration is recommended to prevent
      infectious complications in patients with necrotizing pancreatitis. Although the
      efficacy of the intravenous administration of protease inhibitors is still a
      matter of controversy, there is a consensus in Japan that a large dose of a
      synthetic protease inhibitor should be given to patients with severe acute
      pancreatitis in order to prevent organ failure and other complications. Enteral
      feeding is superior to parenteral nutrition when it comes to the nutritional
      support of patients with severe acute pancreatitis. The JPN Guidelines recommend,
      as optional measures, blood purification therapy and continuous regional arterial
      infusion of a protease inhibitor and antibiotics, depending on the patient's
      condition.

PMID- 16463211
TI  - JPN Guidelines for the management of acute pancreatitis: surgical management.
AB  - Acute pancreatitis represents a spectrum of disease ranging from a mild, self
      limited course to a rapidly progressive, severe illness. The mortality rate of
      severe acute pancreatitis exceeds 20%, and some patients diagnosed as mild to
      moderate acute pancreatitis at the onset of the disease may progress to a severe,
      life-threatening illness within 2-3 days. The Japanese (JPN) guidelines were
      designed to provide recommendations regarding the management of acute
      pancreatitis in patients having a diversity of clinical characteristics. This
      article sets forth the JPN guidelines for the surgical management of acute
      pancreatitis, excluding gallstone pancreatitis, by incorporating the latest
      evidence for the surgical management of severe pancreatitis in the Japanese
      language version of the evidence-based Guidelines for the Management of Acute
      Pancreatitis published in 2003. Ten guidelines are proposed: (1) computed
      tomography-guided or ultrasound-guided fine-needle aspiration for bacteriology
      should be performed in patients suspected of having infected pancreatic necrosis;
      (2) infected pancreatic necrosis accompanied by signs of sepsis is an indication
      for surgical intervention; (3) patients with sterile pancreatic necrosis should
      be managed conservatively, and surgical intervention should be performed only in
      selected cases, such as those with persistent organ complications or severe
      clinical deterioration despite maximum intensive care; (4) early surgical
      intervention is not recommended for necrotizing pancreatitis; (5) necrosectomy is
      recommended as the surgical procedure for infected pancreatic necrosis; (6)
      simple drainage should be avoided after necrosectomy, and either continuous
      closed lavage or open drainage should be performed; (7) surgical or percutaneous
      drainage should be performed for pancreatic abscess; (8) pancreatic abscesses for
      which clinical findings are not improved by percutaneous drainage should be
      subjected to surgical drainage immediately; (9) pancreatic pseudocysts that
      produce symptoms and complications or the diameter of which increases should be
      drained percutaneously or endoscopically; and (10) pancreatic pseudocysts that do
      not tend to improve in response to percutaneous drainage or endoscopic drainage
      should be managed surgically.

PMID- 16463213
TI  - Management strategy for acute pancreatitis in the JPN Guidelines.
AB  - The diagnosis of acute pancreatitis is based on the following findings: (1) acute
      attacks of abdominal pain and tenderness in the epigastric region, (2) elevated
      blood levels of pancreatic enzymes, and (3) abnormal diagnostic imaging findings
      in the pancreas associated with acute pancreatitis. In Japan, in accordance with
      criteria established by the Japanese Ministry of Health, Labour, and Welfare, the
      severity of acute pancreatitis is assessed based on the clinical signs,
      hematological findings, and imaging findings, including abdominal contrast
      enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Severity
      must be re-evaluated, especially in the period 24 to 48 h after the onset of
      acute pancreatitis, because even cases diagnosed as mild or moderate in the early
      stage may rapidly progress to severe. Management is selected according to the
      severity of acute pancreatitis, but it is imperative that an adequate infusion
      volume, vital-sign monitoring, and pain relief be instituted immediately after
      diagnosis in every patient. Patients with severe cases are treated with broad
      spectrum antimicrobial agents, a continuous high-dose protease inhibitor, and
      continuous intraarterial infusion of protease inhibitors and antimicrobial
      agents; continuous hemodiafiltration may also be used to manage patients with
      severe cases. Whenever possible, transjejunal enteral nutrition should be
      administered, even in patients with severe cases, because it seems to decrease
      morbidity. Necrosectomy is performed when necrotizing pancreatitis is complicated
      by infection. In this case, continuous closed lavage or open drainage (planned
      necrosectomy) should be the selected procedure. Pancreatic abscesses are treated
      by surgical or percutaneous drainage. Emergency endoscopic procedures are given
      priority over other methods of management in patients with acute gallstone
      associated pancreatitis, patients suspected of having bile duct obstruction, and
      patients with acute gallstone pancreatitis complicated by cholangitis. These
      strategies for the management of acute pancreatitis are shown in the algorithm in
      this article.

PMID- 16463215
TI  - [Deep brain stimulation and motor cortex and spinal cord stimulation in the
      treatment of movement disorders and pain syndromes -- the theoretical baseline
      and practical guidelines].
AB  - The authors present the current views on the use of electrical stimulation in
      selected movement disorders (Parkinson's disease, dystonia) and pain syndromes
      (central and neuropathic pain) refractory to pharmacological therapy. Stimulation
      should be applied in cases with an established diagnosis (especially Parkinson's
      disease and dystonia) and with a lack of efficacy despite the best available
      medical therapy. Therefore it should be the last treatment option, except of
      generalized dystonia, where it seems to be nowadays the treatment of choice.
      Suggested selection criteria are based on experience of different centers and on
      current medical literature. They are published to make the procedure more
      rational and more available in Poland.

PMID- 16463216
TI  - [An evaluation of the accessibility of early post-stroke comprehensive
      rehabilitation in Poland].
AB  - BACKGROUND AND PURPOSE: According to the European Stroke Initiative
      recommendations every stroke patient should undergo rehabilitation; its program
      should be tailored according to the individual needs of the patient. The aim of
      our study was to evaluate the accessibility of comprehensive early stroke
      rehabilitation at neurological departments in Poland. MATERIALS AND METHODS: We
      have sent a questionnaire evaluating neurological and rehabilitation departments
      in Poland, where stroke patients are treated and undergo early rehabilitation. We
      divided them into 5 categories -- classes from A to F: class A -- having
      comprehensive rehabilitation (kinesitherapy minimum 60 minutes/day, speech
      therapy minimum 30 minutes for 5 days a week and rehabilitation of other
      cognitive impairments and group kinesitherapy at rehabilitation departments); B -
      having the possibility of all types of therapy, but is done less frequently; C -
      kinesitherapy and speech therapy; D -- kinesitherapy and cognitive
      rehabilitation; E -- only kinesitherapy. We also separated neurological
      departments without trained rehabilitation staff. RESULTS: We obtained responses
      from 191 of 215 (88.8%) neurological departments. According to criteria: 26 class
      A, 38 class B, 50 class C, 2 class D, 73 class E, 2 without specialized
      rehabilitation staff. We received filled questionnaires from 115 of 172 (66.9%)
      rehabilitation departments. According to criteria: 11 class A, 31 class B, 28
      class C, 4 class D and 41 class E. CONCLUSION: Only 14% of all neurological
      departments and 10% of rehabilitation departments administered comprehensive
      early stroke rehabilitation in Poland. Improvement of comprehensive
      rehabilitation accessibility in Poland is necessary for lowering the number of
      disabled post-stroke patients.

PMID- 16463217
TI  - [Bickerstaff's brainstem encephalitis -- an analysis of clinical and MRI
      findings].
AB  - BACKGROUND AND PURPOSE: Bickerstaff's brainstem encephalitis (BBE) is a very
      uncommon central nervous system disease. Its etiology remains unknown but it is
      postulated that BBE has an autoimmunologic origin. BBE is characterized by acute
      ophtalmoplegia, ataxia, pyramidal paresis and disturbance of consciousness. A
      special pattern of changes in magnetic resonance imaging (MRI) is characteristic
      of BBE. Lesions are located mainly in the brainstem. The aim of this paper is to
      analyze the clinical course and MRI changes in our own cases of BBE. MATERIAL AND
      METHODS: We have analyzed medical records, clinical findings and MRI images of
      the patients with BBE diagnosis established in our Department of Neurology in the
      years 1998-2004. RESULTS: During that period 4 cases of BBE were diagnosed with
      clinical sings of acute brainstem lesion and MRI imaging suggestive of BBE. In
      our patients we have observed ophtalmoplegia, ataxia, disturbances of
      consciousness and pyramidal signs. Two patients had a monophasic and 2 remitting
      relapsing course of the disease. In all four cases we have seen on T2-weighted
      images large, irregular hyperintense lesions in the brainstem, especially in the
      pons, midbrain and medulla, but also in one case in the thalamus and vermis of
      the cerebellum. Patients were treated with steroids, plasmapheresis or acyclovir
      or a combination of these methods. We observed a complete recovery in two cases
      and significant improvement in the other two lasting more than two years
      confirming a relatively good prognosis in BBE. CONCLUSIONS: BBE despite severe
      initial presentation usually has a good prognosis. MRI plays critical role in the
      diagnosis of BBE.

PMID- 16463218
TI  - [Soluble CD40 and soluble CD40L concentrations in the serum and the cerebrospinal
      fluid of patients with tick borne encephalitis and neuroborreliosis].
AB  - BACKGROUND AND PURPOSE: The interaction between CD40 and CD40L is essential in
      generating of an immunological response also intrathecally. The aim of the study
      was estimation of a concentration soluble form of CD40, CD40L (CD154) in the
      bacterial and viral inflammation of the central nervous system in two
      compartments - blood circulation and intrathecally, before and after the
      treatment. MATERIAL AND METHODS: sCD40 and sCD40L were tested twice before and
      after treatment in pairs serum and CSF of 40 patients treated in the Dept. of
      Infectious Diseases and Neuroinfections. Patients were divided in two groups:
      (n=20) patients with tick borne encephalitis (TBE) (group I, n=20) and patients
      with neuroborreliosis in the form of lymphocytic meningitis (group II, n=20).
      ELISA assays were performed. RESULTS: Significantly increased concentrations of
      sCD40, sCD40L in CSF (higher in neuroborreliosis) were measured. We found also an
      increased concentration of sCD40L in inflammatory CSF in both tested groups (in
      neuroboreliosis lasting also after 4 weeks of treatment), compared with the
      control group (below the detection limit in normal CSF). CONCLUSIONS: Results of
      estimation of the sCD40 and sCD40L concentrations indicate their role in the
      intrathecal inflammation process of bacterial and viral etiology. The increased
      serum concentration of sCD40L in TBE and CD40 in neuroborreliosis indicate that
      peripheral activation of the immunological system persists after cessation of
      treatment and after the clinical recovery. The defense mechanisms are more
      pronounced in neuroborreliosis than in tick borne encephalitis.

PMID- 16463220
TI  - [Eye movements dysfunctions in Alzheimer's disease].
AB  - The author reviews two decades of clinical research directed towards the links
      between disturbances of the oculomotor functions and the severity and progress of
      Alzheimer's disease. Two basically different streams of research are identified.
      The first based on precise, quantitative examination of automatic or reflexive
      eye movements, including saccadic refixation and smooth pursuit. Using both
      predictable and random changes of the stimuli parameters, researchers have
      isolated the oculomotor functions of prediction and planning that relate to more
      advanced processing compared to the simple stimulus-driven responses. Disorders
      of the smooth eye movement control and of saccadic refixation have been used for
      quantifying the motor dysfunction in Alzheimer's disease. The second stream of
      research has been targeted on more cognitive components and their expression in
      visual interactions with the surroundings, with subjects exposed to deliberated
      modified visual environments, that would normally evoke curiosity and emotional
      responses, and modulate awareness.

PMID- 16463219
TI  - [Absence of echoviral RNA sequences in medulla oblongata samples taken from
      patients who died of ALS].
AB  - BACKGROUND AND PURPOSE: The role of viral infection in the pathogenesis of ALS
      has been raised many times in the previous papers. The presence of an enterovirus
      genome has previously been confirmed using PCR RT and PCR in situ in spinal cord
      tissue samples taken from patients who died of ALS. Viral genome sequencing has
      also been used to show 91% and 88% homogeneity with ECHO 6 and 7 viruses,
      respectively. A year later the same method did not confirm the presence of the
      virus in spinal cord fragments taken from 30 patients who died of ALS nor in an
      18 person control group. The present study was aimed to find persistent ECHO 6
      and 7 viral infections in tissue samples taken from patients who died of ALS.
      MATERIAL AND METHODS: RNA was isolated from frozen medulla oblongata samples
      taken from six patients who died of ALS (hospitalized in the Neurological Clinic
      CSK AM in the years 2000-2002). The presence of RNA was confirmed using RNA beta
      actine. Oligo 2 and 3 as well as pEforward and pErevers primers were used for
      amplification. RESULTS: All samples returned negative results. CONCLUSIONS: In
      the samples studied no correlation was found between ECHO 6 and 7 viral
      infections and ALS.

PMID- 16463221
TI  - [Functional imaging in movement disorders].
AB  - Parkinsonian syndromes in the early stage are often misdiagnosed in the general
      practice. Neuroimaging brings information about changes in the anatomical
      structure of the brain, which are not typical of movement disorders. The
      introduction of a functional imaging with the use of presynaptic tracers of the
      dopaminergic system enables proving nigrostriatal degeneration and supporting the
      clinical diagnosis of Parkinsonism even in the early phase of the disease.
      Availability of the single photon emission computer tomography (SPECT) imaging in
      the nuclear medicine departments gives an opportunity to introduce this
      neuroimaging method in Poland. In this review we present methods of functional
      imaging of the brain, particularly of the dopaminergic pathway with the use of
      SPECT tracers. The role of functional imaging in movement disorders workup for
      the neurologist is discussed.

PMID- 16463222
TI  - [Role of perfusion imaging in computed tomography in diagnostics of cerebral
      gliomas].
AB  - CT perfusion is a new diagnostic method which enables imaging of the hemodynamics
      of tissues and organs. Until now most of the publications have been focused on
      the use of this technique to assess acute stroke. The aim of the presented work
      is to show the role of CT perfusion in the diagnosis of cerebral gliomas. These
      tumors are characterized by intensive vascularity which results in an increased
      blood volume (CBV), blood flow (CBF) and permeability surface (PS) values in
      perfusion CT examination. A correlation has been reported between perfusion
      parameters and the histopathological tumor grade. CT perfusion provides
      morphological and functional information which is useful in the diagnosis,
      planning treatment strategies and monitoring of the therapeutic effect in
      cerebral gliomas.

PMID- 16463223
TI  - [Alzheimer's disease and HSV-1 infection].
AB  - Alzheimer's disease is a complex neurodegenerative disorder. Several risk factors
      have been reported and compiled from genetic and epidemiological studies. Many
      theories on the cause of Alzheimer's disease have been proposed over the past.
      Amyloid hypothesis is still the most important one and guides a lot of scientific
      research on AD. But there is general consent that amyloid deposits are the
      products of degenerating neurons, not a cause of degeneration. Recently,
      epidemiological data for the correlation between HSV-1 infection and AD have been
      collected. It was revealed that HSV-1 is present in a latent form in the brains
      of a high proportion of elderly people and is a risk factor for AD in carriers of
      APOEepsilon4. On the other hand, there is negative evidence for HSV-1 as a risk
      factor of APOEepsilon4 positive AD cases. Finally, some investigations raise a
      possibility that viruses other than HSV-1 may influence Alzheimer's disease. In
      the present paper the possible role of HSV-1 infection in pathology of AD is
      discussed.

PMID- 16463224
TI  - Bilateral basal ganglia infarction following resection of a right parietal
      parasagittal dural tumour requiring sinus repair -- an atypical complication of
      an atypical venous drainage.
AB  - The case of a 68-year old woman who underwent surgery for a right parietal
      parasagittal dural tumour is reported. In the preoperative angiography the
      straight sinus failed to show. During tumour resection the lateral wall of the
      parietal superior sagittal sinus was opened and reconstructed. Postoperatively,
      the patient remained unresponsive. A computerized tomography scan revealed
      bilateral infarction of the basal ganglia. Angiography showed an occlusion of the
      superior sagittal sinus with hypervolaemia of the deep venous system. The patient
      did not recover. We conclude that patency of the superficial venous drainage
      system can be mandatory for drainage of the basal ganglia in cases with deep
      venous obstruction. To our knowledge, this is an extremely rare complication of
      neurosurgery in cortical supratentorial areas.

PMID- 16463225
TI  - [The indications for occipito-cervical fixation. A report of three cases].
AB  - Lesions of the cranio-vertebral junction which affect bony structures and
      ligaments may cause instability and compression of the nervous and vascular
      structures. The goal of surgery is decompression of these structures and
      stabilization. The paper presents indications for performing the stabilisation
      procedure with CCD implementation in three patients suffering respectively from
      rheumatoid arthritis and neoplastic disease. In one patient spinal instability
      and spinal cord compression were due to rheumatoid disease and surgery included
      anterior spinal decompression in connection with posterior stabilisation. In two
      patients with neoplasms the retromandibular decompression with posterior
      stabilisation was performed.

PMID- 16463226
TI  - [An abscess of the piriforme muscle as a rare cause of sciatic neuralgia. A case
      report].
AB  - The rare cause of sciatic neuralgia, an abscess in the sciatic foramen, is
      presented. The most common causes of sciatic neuralgia are discussed. We analyse
      correlations between symptoms found in a young woman and anatomical structures of
      the supra- and infrapiriforme foramen and their neighborhood.

PMID- 16463227
TI  - [Peri-interventional risk in 1,384 cardiac catheterizations in patients aged 80
      years or older].
AB  - BACKGROUND AND OBJECTIVE: Because of the rising life expectancy in the
      industrialized countries, ever more cardiac catheterizations are performed in
      patients aged 80 years or older. Little is known about the incidence of peri
      interventional events in this age group. PATIENTS AND METHODS: Between January
      1996 and September 2000, a total of 1,085 patients of that age (mean 82.6 +/- 2.6
      years) underwent cardiac catheterization and intervention (3% of a total of
      43,517 cardiac catheterizations). RESULTS: 827 patients (77%) had significant
      coronary artery stenoses. 373 of them (45%) were treated with balloon
      angioplasty, with or without stenting, and 331 (40%) underwent aortocoronary
      bypass procedures. 31 patients died while in hospital, 17 of them having been in
      cardiogenic shock on admission. Peri-interventional events, including damage to
      artery at the site of catheter entry occurred in 2.1% of patients undergoing
      diagnostic cardiac catheterization and in 11.6% in connection with a percutaneous
      interventional procedure. CONCLUSION: Both cardiac catheterization and
      interventional procedures can be done with a justifiable risk in patients aged 80
      years or older. These cardiac investigations/interventions should not be withheld
      in this group of patients for reasons of age.

PMID- 16463228
TI  - [Obesity surgery: the refusal rate of health care cost reimbursement despite
      expert opinion].
AB  - BACKGROUND AND OBJECTIVE: Surgery is an effective method to treat patients with
      morbid obesity. However health insurance companies frequently refuse to cover the
      costs for the procedure despite an existing DRG-code for this operation.
      Individual medical expertise are necessary to receive reimbursement. In the
      present study the acceptance of medical expertise to receive cost coverage was
      analysed in our patients of the years 2000-2003 eligible for obesity surgery.
      PATIENTS AND METHODS: 617 medical expertise of patients eligible for obesity
      surgery in our hospital were reviewed and the acceptance rate was evaluated.
      Parameters such as body mass index, personal medical history, diets, comorbidity
      and prognosis were included. Expertise were submitted to the health care
      insurance companies and in case of acceptance the operation was performed.
      RESULTS: The average age of our patients was 39.1 +/- 11.2 years, 72.1% were
      female, 27.9% male. The average BMI was 47.5 +/- 7.4 kg/m2. There was a high
      incidence of comorbidity in these patients (58.7% arterial hypertension, 38.6%
      diabetes mellitus, 95.8% dyspnoea, 96.1% arthropathy, 89.0% psychosocial
      disorders). The difference between accepted and non-accepted regarding these
      secondary complications was not significant. 209 patients (33.8%) were operated.
      14 patients of these paid the costs themselves. Only in 195 cases (31.6%) the
      health care insurance company covered the costs for the operation. CONCLUSION:
      The high number of refusals of medical expertise is not justified in view of the
      strict criteria for indication, the high frequency of comorbidity and the good
      results after the operation.

PMID- 16463229
TI  - [Toxic-shock-like-syndrome caused by beta-hemolysing group G streptococci in a
      multimorbid patient with erysipelas].
AB  - HISTORY AND FINDINGS: A 41-year-old, obese man with a history of incomplete
      paraplegia of both legs and chronic venous insufficiency with stasis dermatitis
      presented with acute respiratory and hyperdynamic hemodynamic failure. He was
      transferred from another hospital to the department of intensive care medicine
      for further diagnosis and treatment. A livid coloured, necrotizing-hemorrhagic
      swelling of the right lower leg was noted. INVESTIGATIONS: Laboratory tests
      revealed an inflammation probably due to bacterial infection, anemia, acute renal
      failure, acute hepatic dysfunction, coagulopathy and lactic acidosis, indicating
      multi-organ failure and septic shock. No focus of sepsis was found at abdominal
      sonography and exploratory laparotomy. Chest X-Ray and computed tomography
      revealed bilateral pneumonia. Doppler ultrasonography of both legs showed acute
      isolated thrombosis of the right posterior tibial vein. TREATMENT AND COURSE: In
      addition to a chronic venous ulcer-necrotizing hemorrhagic erysipelas had
      developed in the right lower leg. A swab taken at surgery and blood cultures grew
      Streptococcus dysgalactiae ssp. equisimilis (group G streptococci, GGS). Despite
      intensive care treatment and high dosage penicillin G therapy the patient died
      two days after admission from septic shock and multi-organ failure. CONCLUSIONS:
      Group G streptococci cause a variety of common and severe infections. Erysipelas
      is infrequently associated with GGS but, much more often, with group A
      streptococci (GAS). This unusual and fulminant case emphasizes the importance of
      considering Streptococcus dysgalactiae as a causative agent in septicemia with
      multiple predisposing factors and soft-tissue infections.

PMID- 16463231
TI  - [Diagnostic and prognostic significance of antibodies against citrullinated
      peptides].
AB  - Antibodies against citrullinated peptides are highly specific for rheumatoid
      arthritis. With second generation ELISA-kits, CCP-antibodies have a specificity
      of > 96 % and a sensitivity of 68 %. CCP-antibodies can be detected several years
      before the onset of clinical symptoms. They are, thus, ideally suited for the
      differential diagnosis between early forms of rheumatoid arthritis and other
      inflammatory arthritides. As CCP-antibodies are associated with aggressive and
      treatment resistant courses of rheumatoid arthritis, their high predictive value
      can be useful in therapeutic strategy decisions in order to verify early
      treatment with disease modifying drugs or biologicals in line with modern
      treatment approaches to start aggressive therapy early to prevent bone erosions.
      In contrast to their role in differential diagnosis and prediction of aggressive
      disease, however, CCP-antibodies are of no value in monitoring treatment as they
      do not change essentially over prolonged periods of time.

PMID- 16463232
TI  - [Reduced drive and impaired cerebral performance: a new perspective on
      chronically low blood pressure].
AB  - The scientific literature on mental impairment in persons with chronically low
      blood pressure (using WHO criteria) is systematically reviewed within its
      physiological context. Subjective symptoms related to hypotension, especially
      tiredness and listlessness have been adequately demonstrated. There are
      consistent findings demonstrating deficits in cognitive functions, especially in
      the fields of concentration and memory. Additionally, contrary to the current
      views, recent studies provide evidence for an impaired regulation of cerebral
      blood flow and reduced cerebral perfusion. The resulting deficits in brain
      function are also reflected in EEG findings. These findings indicate that the
      marginal attention paid to chronic hypotension in research and clinical practice
      is no longer justified.

PMID- 16463233
TI  - [Paradigm shift in public health -- redirection in medicine. Prospects,
      prevention and personalization].

PMID- 16463234
TI  - [What does the bleeding time predict?].

PMID- 16463236
TI  - [Weight loss, abdominal pain and anemia as consequences of a vacation trip. Re
      the article from DMW 40/2005].

PMID- 16463237
TI  - [New options for the pharmacotherapy of Alzheimer disease after the approval of
      memantine? Re the article from DMW 8/2005].

PMID- 16463238
TI  - [Order of merit of the Federal Republic of Germany for Professor Dr. Johannes
      Gostomzyk].

PMID- 16463239
TI  - [New chance for health promotion law. Summary of the article "New chance for
      health promotion law"].
AB  - At the end of the last term of legislation the health promotion law which had
      passed Parliament (Bundestag) finally failed as it was not agreed upon by the
      States (Lander). The complex interrelation between federal level, states and
      social insurance organisations was neglected. The coalition of Christian
      Democrats and Social Democrats which was formed in autumn 2005 has agreed to
      launch a health promotion law, but precise statements to contentious issues are
      missing.

PMID- 16463240
TI  - [Treatment motivation and results of inpatient psychotherapy for women with
      depressive disorders: a prospective study].
AB  - Whether the treatment results in inpatient psychotherapy are significantly
      influenced by the patient's motivation is a subject of discussion. The goal of
      this study was to assess whether the primary motivation for therapy in depressive
      women influences the results of psychotherapeutic treatment. In a prospective
      study, the monitored results from 64 female inpatients (32 who were highly
      motivated to enter therapy, and 32 who were minimally motivated) were compared to
      each other. The period of observation was six weeks. As instruments of
      assessment, the Fragebogen zur Therapiemotivation (FMP) (Questonnaire on
      Motivation for Entering Therapy) and the Beck Depression Inventory (BDI) were
      aministered upon admission; after the fourth and sixth weeks of therapy, the
      Veranderungsfragebogen des Erlebens und Verhaltens (VEV) (Questionnaire of
      Changes in Experience and Behavior) was administered as well. All patients who
      had applied for a pension were found in the group of less motivated patients and
      consolidated into a subgroup. The analysis was carried out according to the
      intent-to-treat principle. The variance analysis for the repeat measurements
      showed significant differences on all the FMP scales and on the BDI (all P<
      0.001). The measurements with VEV likewise resulted in a significant difference
      (P< 0.01). The subgroup of "pension patients" showed significantly less change in
      all three of the above measurements. Patients with depressive symptomology who
      essentially are relatively highly motivated for therapy could profit
      significantly more from inpatient psychosomatic treatment than those who are less
      motivated. Establishing and developing motivation prior to inpatient
      hospitalization could possibly contribute to more efficient and cost-effective
      clinical treatment. Where legal proceedings pertaining to a pension are pending,
      relatively less motivated patients fare significantly worse not only in their
      motivational development for therapy, but also in their final treatment results.
      It should be noted, however, that the relatively small random sample, the
      restricted blinding, which was only partially possible, could have led to
      possible distortions.

PMID- 16463241
TI  - [Independent dental patient consultation service--experiences of the information
      center for the Rhine-Neckar district].
AB  - Patients should be the focus of health care - or so resounds the frequently heard
      cry of politicians, consumer protection groups and patient representatives. It
      cannot be denied that the increased co-determination of the insured and of
      patients in the health service is a sign of the times. Demanding ever increasing
      health insurance premiums and exacting higher additional contributions from
      patients on the one hand without increasing their say and their rights on the
      other hand meets with little sympathy. Spouting like a mantra about "personal
      responsibility", the "voice of the patient" or the "sovereignty of the consumer"
      in talk-shows or studio debates is not sufficient. Words must be followed up by
      actions in order to give patients the necessary skills to enable them to make
      autonomous decisions. One step in this direction is the model of an independent
      dental consumer and patient advisory service in the Rhine-Neckar district health
      authority presented here and sponsored by the central associations of the health
      insurance companies in the scope of the funding provided under section sign 65 b
      SGB V [Social Security Code]. Since 2001 over 4000 people seeking advice have
      received information about dental treatment, planned therapies or legal issues.
      More than half of those seeking advice are between 40 and 70 years old and the
      number of women outweighs the number of men. The majority of patients want an
      independent second opinion, demonstrating the limits of call centres or Internet
      advice services. The anonymity of the consultation is an important factor for
      those seeking advice. The successful integration of the advisory service is
      evident, not only from the high number of consultations, but also from the fact
      that the majority of those seeking advice have been referred to the service by
      their respective health insurance company. For various reasons it can be assumed
      that there will be an increasing demand for qualified dental advice. It is
      therefore incumbent on health policy to create a regulatory framework and to
      ensure the funding on a broader base. Wherever possible the public health service
      can take control, ensuring the independence of the advisory service and
      guaranteeing that group interests remain outside.

PMID- 16463242
TI  - [Disease Management Program for diabetes mellitus type 2: cooperation or
      resistance of the general practitioner].
AB  - AIM: of the study was to seize the attitudes of General Practitioners (GPs)
      towards the disease management program (DMP) for type 2 diabetes implemented in
      summer 2003 in Germany. Moreover we were interested in the way GPs realise the
      program in daily practice, e. g. how many patients and which patients they
      include. METHOD: A postal questionnaire was sent twice to all GPs in the region
      of Hamburg (n = 1.230), in November 2003 and in December 2004. Response rate
      without reminder was 20 respective 16 percent. RESULTS: In 2004 81 percent of the
      GPs taking part in the survey participate in the DMP. These doctors include a
      third of their patients with type 2 diabetes into the program. 65 percent of the
      GPs nevertheless do not believe, that the patients will benefit from the program.
      47 percent of the participating GPs object to DMP in general. Only 66 percent say
      they follow the DMP guidelines for pharmacotherapy. Half of the doctors state
      they actively canvass patients for the program, while one fifth says they advice
      patients against participation. The GPs participate in first line to supply the
      demand of the patients and because of the public pressure less because they think
      the DMP is good in respect of content. In 2003 critics and pessimism regarding
      benefit for patients were even stronger than in 2004. CONCLUSIONS: GPs
      participate in the DMP diabetes half-heartedly and with doubts. The results
      suggest selections in the inclusion of patients. Further research should find out
      whether patients being likely to profit from the DMP are systematically not
      included.

PMID- 16463243
TI  - [Determinants of hospital admission--investigation by case vignettes].
AB  - Unexplained differences in the density of in-patient management in one federal
      state in Germany led to a regional survey of physicians in independent and
      hospital practice, which aimed to describe more precisely the determinants of
      referral and admission behaviour. Brief typical case descriptions (vignettes)
      were designed, as an instrument of data collection, dealing with two examples of
      management problems: upper and lower abdominal pain. The urgency of inpatient
      treatment was ranked using clinical scores and guidelines. Social characteristics
      for the patient (age, gender, social situation, preference for/against
      hospitalisation, day of the week on which the patient presented) were randomly
      assigned to the case vignettes. Each physician was asked by mail to decide on the
      management of 10 upper and 10 lower abdominal vignettes each. The physicians were
      also asked to provide additional information on the characteristics of their
      practice or hospital. The data were analysed using multivariate hierarchical
      models. A 28 % response rate meant that vignettes were available from 455 general
      practitioners and internal medicine specialists in independent practice, as well
      as 261 hospital surgeons and internal medicine specialists, together with
      responses from 31 physicians from the medical service of the German statutory
      health insurance (MDK). 7376 upper abdominal and 7335 lower abdominal vignettes
      were analysed. Admission rates reflected the graded severity of the symptoms
      built into the vignettes. Hospital physicians wanted to admit the vignette
      patients much more frequently than physicians in independent practice wished to
      refer them. Older patients, independent of symptoms, were more frequently
      referred or admitted than younger patients. In the case of acute symptoms it is
      the day of the week when the patient consulted the physician and in the case of
      elective surgery the patient's preference that are important for hospitalisation.
      The results show that medical decisions on case management are made using
      reasonable problem-specific preferences. The probability of actually instigating
      admission was, other things being equal, much higher in hospital physicians than
      in office-based physicians. As an instrument of comparative research into medical
      care, case vignettes have practical advantages in relation to medical audits and
      standardised patients. They can also be used for teaching, examining, documenting
      and quality assurance purposes.

PMID- 16463244
TI  - [Equipment and use of equipment in nursing homes].
AB  - AIM OF THE STUDY: The aim of this research study was to describe the provision of
      aids and their use in the transport of residents. The study was also intended to
      analyse prior experience with the methods and concepts of resident transfer,
      paying due attention to back problems. The resulting knowledge is to support work
      on the implementation of procedures in geriatric in-patient care which are suited
      to workers with back problems. METHODS: This is a cross-sectional study, in which
      217 nurses and 43 superior nurses were interviewed, with the help of a
      standardised questionnaire which they are expected to complete. RESULTS: The
      majority of those questioned felt that they were not well informed about the
      availability of aids. This is reflected both in the deficient equipment with the
      aids and in how rarely they are used. The superior nurses regarded themselves as
      being rather better informed. In general, there are fewer small than large aids
      in the institutions and these are also used more rarely. "Lack of time" and "lack
      of acceptance by the residents" were the main reasons given for lack of use.
      About half of the superior nurses and nurses feel that they are well or very well
      informed about mobility concepts and working methods which spare the back.
      According to this, these concepts are only applied in a quarter of old people's
      homes, although training is more frequent. Instruction in the use of aids takes
      place too rarely. This can be concluded from the evaluation of the data from the
      superior nurses and the 109 spontaneous comments from the nurses, who not only
      advocated the purchase of the aids, but also emphasised the need for more
      information and training. CONCLUSIONS: The results indicate that current work on
      equipment with aids and training in their use must be optimised and must also
      incorporate recent advances in scientific knowledge. Implementation of specific
      risk assessment analyses of stress at work and regular training in dealing with
      aids could help to support the use of aids for geriatric in-patients.

PMID- 16463246
TI  - [Pulmonology and mechanical ventilation].

PMID- 16463247
TI  - [Airway sensory nerve and tachykinins in asthma and COPD].
AB  - The airway nerve has gained importance in the field of respiratory research as it
      is known to have the capacity to release numerous mediators which can cause
      pulmonary effects in the airways. Meanwhile, a broad range of stimuli including
      capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone,
      inflammatory mediators and cold dry air have been shown to activate sensory nerve
      fibres to release neuropeptides such as the tachykinins substance P (SP) and
      neurokinin A (NKA) to mediate neurogenic inflammation. SP is synthesized in cell
      bodies of airway neurons of the trigeminal, jugulare and nodose ganglia.
      Following their release, tachykinins are degraded by neutral endopeptidase (NEP)
      and an angiotensin-converting enzyme. Tachykinins have been proposed to play an
      important role in human respiratory diseases such as bronchial asthma und chronic
      obstructive diseases (COPD) as they have been shown to have potent effects on the
      tone of airway smooth muscle, airway secretions, bronchial circulation and on
      inflammatory and immune cells by activation of the neurokinin-1 (NK-1) and
      neurokinin-2 (NK-2) receptors. Recently, new tachykinins such as virokinin and
      hemokinin were identified and characterised. Different aspects of the neurogenic
      inflammation have been well studied in animal models of allergic airway
      inflammation, but only little is known about the role of neurogenic airway
      inflammation in human diseases. To address the precise role of tachykinins and
      airway sensory nerves in human asthma und COPD, experiments on sensory nerve
      sensitisation and neuro-immune interaction have to be carried out in future
      studies.

PMID- 16463248
TI  - [New occupational disease (BK 4112): lung cancer due to silicium dioxide].

PMID- 16463249
TI  - [Talc pleurodesis in malignant pleural effusions].
AB  - Pleural effusions associated with malignancy--either malignant or paramalignant
      diseases--were found in ca. 20% of these patients. Large pleural effusions cause
      mainly dyspnoea but also cough and chest pain. The presence and degree of
      dyspnoea depend on the size of the effusion and the patient's underlying
      pulmonary function. In acute cases and large effusions immediate chest drainage
      is indicated in symptomatic patients, followed by the treatment of the underlying
      disease, e. g. chemotherapy. The most effective therapy for controlling
      reiterated malignant pleural effusions is the thoracoscopic talc poudrage (2.5-10
      g) which has been shown to have a success rate of > 90%. Talc induces a broad
      inflammatory reaction involving mesothelial cells of the pleura, coagulation
      parameters, fibroblast proliferation eventually leading to symphysis of the
      pleura. This procedure is reserved for patients who are in good general
      conditions, who are expected to have a reasonably long survival, and who failed
      chemical pleurodesis. A good predictor for longer survival time is a Karnofsky
      Performance Scale > or = 40 indicating a survival time > 30 days, which therefore
      should be considered prior to the procedure. The adult respiratory distress
      syndrome (ARDS) is the most important complication initially observed in the US
      in up to 9% of all cases. ARDS incidence was strongly related to high number
      (50%) of small talc particles < 15 microm. In summary, talc poudrage or slurry
      (talc particle size > 10 microm) in malignant pleura effusions is a safe and
      effective method to induce pleura symphysis. Complaints and complications such as
      chest pain, transient fever, and empyema are rare or very are which are almost
      exclusively related to the therapeutic procedure itself.

PMID- 16463251
TI  - [Pathophysiological basis of mechanical ventilation].
AB  - Mechanical ventilation is required if ventilatory insufficiency is present. This
      is typically indicated by hypercapnea. Hypoxemia occurs secondary to
      hypoventilation. Usually overload of the respiratory muscles (ventilatory pump)
      will be the underlying mechanism, for the most part caused by acute or chronic
      disease. In case of sole hypoxemia mechanical ventilation will only be indicated
      if the oxygen-content (equals oxygen saturation x haemoglobin x 1.39) drops below
      a critical threshold or if ventilatory pump failure is imminent on account of the
      underlying disease (eg. pneumonia). The background of our recommendations is to
      avoid potential damage caused by mechanical ventilation. Especially high
      inspiratory pressures and oxygen concentrations can be harmful to the lung.
      Therefore every case has to evaluated for individual target parameters of
      ventilation. The use of the oxygen-content instead of the arterial oxygen
      pressure as the target parameter will usually lead to a more careful ventilation.
      Cardiogenic pulmonary oedema is an exception to this rule since inspiratory
      positive pressure and PEEP will result in improved diffusion as well as reduction
      of preload and work of breathing. In recent years progress has been made on the
      field of ventilation access especially in severe and acute cases. Non-invasive
      ventilation is superior to invasive ventilation in patients with exacerbated COPD
      since it improves outcome effectively. This is being caused by a decline in
      ventilator associated pneumonias, most likely because non-invasive ventilation
      allows patients to clear their secretions by coughing, resulting in improved lung
      clearance. Controlled ventilation allows optimal unloading of the respiratory
      muscles which have been overloaded by the underlying disease. Application of a
      controlled ventilation mode in acute disease will usually require some kind of
      sedation. Assisted ventilation will result in improved gas exchange but only
      incomplete unloading of respiratory muscles and therefore delayed restitution.
      Permanent controlled ventilation under sedation for a prolonged period (days)
      requires intermittent periods of assisted- or spontaneous breathing in order to
      avoid atrophy of the respiratory muscles. This review summarizes background
      information on the nature of the derangement, the relation between oxygen supply
      and consumption under special consideration of respiratory muscle insufficiency
      and impact of different ventilation modes.

PMID- 16463252
TI  - [CAPNETZ: Competence network for community acquired pneumonia in Germany].

PMID- 16463253
TI  - [Curriculum pneumologicum 2005. Part 2].

PMID- 16463254
TI  - Optimum blood sampling time windows for parameter estimation in population
      pharmacokinetic experiments.
AB  - Clinical trials requiring the collection of pharmacokinetic information often
      specify blood samples to be taken at fixed times. This may be feasible when trial
      participants are in a controlled environment such as in early phase clinical
      trials, however it becomes problematic in trials where patients are in an out
      patient clinic setting such as in late phase drug development. In such a
      situation it is common to take blood samples when it is convenient for all
      involved and may result in data that are uninformative. This paper proposes an
      approach to pharmacokinetic study design that allows greater flexibility as to
      when blood samples can be taken and still result in data that allows satisfactory
      parameter estimation. The sampling window approach proposed in this paper is
      based on determining time intervals around the D-optimum pharmacokinetic sampling
      times. These intervals are determined by allowing the sampling window design to
      result in a specified level of efficiency when compared to the fixed times D
      optimum design. Several approaches are suggested for dealing with this design
      problem.

PMID- 16463255
TI  - Determination of toxic carbonyl compounds in cigarette smoke.
AB  - Toxic carbonyl compounds, including formaldehyde, malonaldehyde, and glyoxal,
      formed in mainstream cigarette smoke were quantified by derivatization-solid
      phase extraction-gas chromatography methods. Cigarette smoke from 14 commercial
      brands and one reference (2R1F) was drawn into a separatory funnel containing
      aqueous phosphate-buffered saline. Reactive carbonyl compounds trapped in the
      buffer solution were derivatized into stable nitrogen containing compounds
      (pyrazoles for beta-dicarbonyl and alpha,beta-unsaturated aldehyde; quinoxalines
      for alpha-dicarbonyls; and thiazolidines for alkanals). After derivatives were
      recovered using C(18) solid phase extraction cartridges, they were analyzed
      quantitatively by a gas chromatograph with a nitrogen phosphorus detector. The
      total carbonyl compounds recovered from regular size cigarettes ranged from 1.92
      mg/cigarette(-1) to 3.14 mg/cigarette(-1). The total carbonyl compounds recovered
      from a reference cigarette and a king size cigarette were 3.23 mg/cigarette(-1)
      and 3.39 mg/cigarette(-1), respectively. The general decreasing order of the
      carbonyl compounds yielded was acetaldehyde (1110-2101 microg/cigarette(-1)) >
      diacetyl (301-433 microg/cigarette(-1)), acrolein (238-468 microg/cigarette(-1))
      > formaldehyde (87.0-243 microg/cigarette(-1)), propanal (87.0-176
      microg/cigarette(-1)) > malonaldehyde (18.9-36.0 microg/cigarette(-1)),
      methylglyoxal (13.4-59.6 microg/cigarette(-1)) > glyoxal (1.93-6.98
      microg/cigarette(-1)).

PMID- 16463256
TI  - Cytotoxic effects and apoptosis induction of atrazine in a grass carp
      (Ctenopharyngodon idellus) cell line.
AB  - Atrazine is a widely used herbicide that was considered to be an endocrine
      disrupter capable of interfering with the synthesis and action of natural
      hormones. In the present study, we found that atrazine was able to cause
      apoptosis in grass carp (Ctenopharyngodon idellus) cells from cell line ZC7901.
      By fluorescent and transmission electron microscopy, the atrazine-incubated cells
      displayed a series of morphological changes, including condensation of the
      nucleus, margination of chromatin to form dense granular caps, and formation of
      apoptotic bodies. Moreover, DNA fragmentation was detected by the TUNEL reaction
      and agarose gel electrophoresis. These typical characteristics of cells
      undergoing apoptosis indicated the occurrence of apoptosis in ZC7901. Apoptosis
      induced by atrazine was dose- and time-dependent and was involved in
      mitochondrial membrane potential (DeltaPsi(m)) disruption, elevation in
      intracellular Ca(2+), generation of reactive oxygen species, and intracellular
      ATP depletion. This study provides the first evidence that atrazine was able to
      induce apoptosis in fish cells, which indicated the existence of a novel
      cytotoxic mechanism caused by atrazine and may improve our understanding of the
      complex relationship between contaminants and aquatic organisms.

PMID- 16463257
TI  - Significance of physicochemical forms of storage in microalgae in predicting
      copper transfer to filter-feeding oysters (Crassostrea gigas).
AB  - Copper distribution has been examined in two microalgae (Haslea ostrearia,
      Diatom; Tetraselmis suecica, Prasinophyceae) exposed to Cu at 30 microg/L(-1).
      Exchangeable copper linked at the cell surface was desorbed using 8
      hydroxyquinoline-5-sulfonate as complexing agent. Then, incorporated copper was
      separated between soluble and insoluble fractions. In addition, algae were
      resuspended in acid solutions, the pHs of which covered the range existing in the
      digestive tract of bivalves. Considering that the soluble fraction is the most
      easily transferred in the food chain and that exchangeable Cu is easily desorbed,
      the percentages of Cu potentially available in microalgae have been assessed.
      These percentages have been compared with those retained in oysters Crassostrea
      gigas fed with contaminated microalgae in previous studies. In H. ostrearia, the
      potentially available fraction of Cu (90%) was very similar to the percentage
      retained by oysters (93%) when the bivalves were acclimated to this food for 3
      weeks. Only half (21%) of the potentially available Cu of T. suecica (42%) was
      readily assimilated in oysters after 3 weeks. This is in agreement with the
      results of the desorption tests at physiological pHs which showed that only 15
      25% of Cu was lost, despite solubilization of other constituents of T. suecica as
      demonstrated by the decrease in their dry weight. Bioavailability determined from
      metal speciation in food allows a relevant prediction of the trophic transfer in
      the case of H. ostrearia, but caution is recommended in generalizing this mode of
      assessment as shown in the case of T. suecica.

PMID- 16463258
TI  - A dose-based modeling approach for accumulation and toxicity of arsenic in
      tilapia Oreochromis mossambicus.
AB  - We proposed an approach to relate metal toxicity to the concentrations of arsenic
      (As) in specific target organs of tilapia Oreochromis mossambicus. The
      relationships among As exposure, uptake, accumulation, and toxicity of tilapia
      were investigated using kinetic and dynamic modeling. The biouptake rate of
      waterborne As through the gills of fish was dependent on exposure concentrations,
      in that the relationship was well described by incorporating Michaelis-Menten
      type uptake kinetics. The fitted bioaffinity parameter and limiting uptake flux
      were 3.07 +/- 2.21 microg/mL(-1) (mean +/- SD) and 2.17 +/- 0.38 microg/mL(-1)/d(
      1), respectively, suggesting that a low As binding affinity of tilapia gills, yet
      a relatively high binding capacity was obtained. The toxicity of As was analyzed
      by determining the lethal exposure concentration associated with a mortality of
      50% (LC50) at different integration times. Our results demonstrate that 96-h and
      incipient LC50s for tilapia are 28.68 (95% CI: 15.98-47.38) and 25.55 microg/mL(
      1), respectively. The organ-specific internal residue associated with 50%
      mortality was estimated by combining the model-predicted toxicokinetic parameters
      and the area-under-curve (AUC)-based time-integrated concentration toxicity
      model. A physiologically based toxicokinetic model was constructed to elucidate
      the principle mechanisms that account for the observed data and to predict the
      kinetics of As in tilapia under different water exposure scenarios. We employed
      the Hill equation model to predict the organ-specific dose-response
      relationships. We used the liver as a surrogate of target sites to assess the As
      toxicity to tilapia because of its higher sensitivity to As toxic effects. The
      predicted mortalities never reach 50% when the tilapia were exposed to waterborne
      As <2 microg/mL(-1). The predicted mortality is, however, slightly higher than
      the observed values before the 10th day in that the profile reached the 70%
      maximum mortality, which is comparable to the observed data when the tilapia were
      exposed to 4 microg/mL(-1). Our results show that a dose-based toxicokinetic and
      toxicodynamic modeling approach successfully links metal exposure to
      bioavailability, bioaccumulation, and toxicity, under variable exposure
      scenarios.

PMID- 16463259
TI  - Cadmium tolerance in the Nile tilapia (Oreochromis niloticus) following acute
      exposure: assessment of some ionoregulatory parameters.
AB  - The Nile tilapia (Oreochromis niloticus) can tolerate very high levels of
      waterborne cadmium. It has one of the highest 96 h LC50 recorded for a freshwater
      teleost fish (14.8 mg/L Cd; hardness 50 mg/L CaCO(3)). Cadmium is known to
      perturb ion balance in teleost fishes. However, in an acute time course
      experiment, plasma Na(+) concentrations were unaffected, and plasma Ca(2+) values
      only decreased after 96 h exposure in a dose-independent manner. Branchial
      Na(+)/K(+)-ATPase activity and alpha-subunit protein level expression in crude
      gill homogenates were not affected by Cd exposure during this period. Branchial
      chloride cell numbers, identified as Na(+)/K(+)-ATPase immunoreactive cells using
      immunohistochemistry, decreased 24 h after exposure but recovered thereafter.
      Histopathological changes did not follow a consistent pattern of variation with
      exposure time, and the alterations noted in gill epithelium were basically
      nonspecific to cadmium. Because of its tolerance, it can be concluded that the
      tilapia O. niloticus would not be a suitable test organism to evaluate sublethal
      toxicity of cadmium and the realistic impact of this pollutant in the
      environment. However, it certainly could contribute significantly to our
      understanding of the toxic mechanism of cadmium exposure in aquatic organisms.
      This is the first work to investigate the effect of waterborne pollutants on
      Na(+)/K(+)-ATPase alpha-subunit protein expression in fish gills.

PMID- 16463260
TI  - Genotoxicity of the marine toxin okadaic acid, in human Caco-2 cells and in mice
      gut cells.
AB  - Micronucleus induction by the diarrhetic shellfish toxin okadaic acid (OA) was
      investigated in two intestinal models, cultured human Caco-2 cells and colon
      epithelial cells of mice treated in vivo. Exposure to OA for 4 and 24 h induced
      dose-responsive increases in the frequency of micronucleated Caco-2 cells; the
      minimum OA doses increasing micronucleus frequency were 20 nM for the 4 h
      treatment and 5 nM for the 24 h treatment. OA treatment of Caco-2 cells also
      resulted in dose- and time-dependent increases in mitotic arrest and
      multinucleated cells. Two experiments were conducted in which mice were treated
      with single oral gavages of 435-610 and 115-1341 microg/kg OA. In the first
      experiment, samples were taken 24 h after the treatment, and the frequencies of
      both micronucleated and mitotic gut cells were increased after treatment with 525
      microg/kg OA. In the second experiment, no increases in micronucleus frequency
      were detected at 24, 36, or 48 h following OA doses of 230 and 115 microg/kg;
      however, an increase in the mitotic index was observed 36 h after a gavage with
      115 microg/kg OA. In this experiment, doses higher than 230 microg/kg were
      rapidly lethal to the mice. Immunohistology with monoclonal OA antibodies showed
      that OA was distributed into the liver at all the sampling times and in the small
      intestine at 24 and 36 h; OA was not detected in the colon. In addition, the
      TUNEL assay indicated that OA induced apoptosis in mouse ileum, liver, and
      kidney. The results of our investigations suggest that OA is aneugenic in Caco-2
      cells, whereas the in vivo data were inconclusive. Further studies should be
      performed in mice using intragastric doses of 230-525 microg/kg OA. Moreover, the
      apoptosis and cell proliferation results indicate that OA can reach organs other
      than colon, indicating further evaluation of the genotoxic potential of OA in
      these organs is warranted.

PMID- 16463261
TI  - Validation and update of a model used to predict copper toxicity to the marine
      bivalve Mytilus sp.
AB  - A model was recently published that relates the toxicity of copper to the most
      sensitive taxa in the U.S. Environmental Protection Agency's criteria database
      (Mytilus sp.) with dissolved organic carbon concentrations in saltwater. This
      model was developed for potential use in risk assessment and in the development
      of site-specific criteria (SSC) for copper in saltwater environments where
      Mytilus sp. is considered an appropriate indicator species. This manuscript
      presents the results of a field validation study of that model. Effective
      concentration 50% (EC(50)) values (n = 21) for seven sites were all predicted by
      the model within the previously established range of acceptability. Slopes and
      intercepts of the two data sets were not significantly different. Consequently,
      the data were pooled, and new equations were developed. Dissolved copper EC(50)
      values were highly correlated (r(2) = 0.76, n = 75, P < 0.0001) across a wide
      range of sample dissolved organic carbon (DOC) concentrations (0.3-12 mg C/L) and
      were explained by the equation EC(50) = 11.22 DOC(0.60). Two updated equations
      are proposed for consideration as a means of estimating site-specific final
      chronic criteria (FCC) and final acute criteria (FAC) for copper in marine and
      estuarine environments (copper FCC(DOC) = 3.59 DOC(0.60); copper FAC(DOC) = 5.61
      DOC(0.60)).

PMID- 16463262
TI  - Sorption of chlorophenoxy propionic acids by organoclay complexes.
AB  - The organoclays Wyoming montmorillonite (SWy-1, Mon), W. R. Grace vermiculite
      (Ver), and Tung-Wei (Tw) soil montmorillonite were prepared to sorb or remove
      chlorophenoxy propionic acids (CPA) pollutants such as 2,4-dichlorophenoxy acid
      (2,4-DP), 2,4,6-tri chlorophenoxy acid (2,4,6-TCP), and pentachlorophenoxy
      propionic acid (PCP). The objective of this study was to evaluate the behavior of
      organoclays that have sorbed three types of CPA and to assess the applicability
      to basaltic-developed iron-rich calcareous soil. This type of soil contains high
      amounts of montmorillonite. The mean-layer charge per formula unit of Mon, Ver,
      and Tw clays, characterized by the alkylammonium method, was 0.27, 0.70, and 0.52
      mol(c)/O(10)(OH)(2), respectively. The sorption isotherms of 2,4-DP, 2,4,6-TCP,
      and PCP sorbed by hexadecyltrimethyl-ammonium (HDTMA organoclay, 150% cation
      exchange capacity) were evaluated. The data on sorption of CPAs fit well with the
      Freundlich isotherm equation. In general, the sorption of three types of CPA by
      the organoclays showed a linear relationship, with a high correlation coefficient
      (r > 0.935). The K(f) value of PCP was the same as that of 2,4,6-TCP sorbed by
      the organoclays and was higher than that of 2,4-DP. However, the 1/n(f) values of
      the three CPAs sorbed by the organoclays did not show significant differences. In
      general, maximum CPA sorption occurred at a pH of approximately 3, but very
      significant differences were observed for the 2,4,6-TCP and PCP sorbed by the
      organoclays. However, there was no significant difference in pH for 2,4-DP
      sorption. This should be related to the solubility and pKa of each CPA. The
      experimental results showed that solubility of 2,4-DP, 2,4,6-TCP, and PCP is a
      function of pH, ionic strength, and temperature.

PMID- 16463263
TI  - Attenuating effects of natural organic matter on microcystin toxicity in zebra
      fish (Danio rerio) embryos -- benefits and costs of microcystin detoxication.
AB  - To contribute to the understanding of joined factors in the environment, impact
      of pure microcystins (-RR and -LF) on zebra fish (Danio rerio) embryos were
      investigated individually and in combination with a natural organic matter (NOM).
      The applied NOM was a reverse osmosis isolate from Lake Schwarzer See (i.e.,
      Black Lake, BL-NOM). Teratogenic effects were evaluated through changes in
      embryonic development within 48 h of exposure. Detoxication activities were
      assessed by the activities of phase II biotransformation enzymes, soluble and
      microsomal glutathione S-transferase (s, mGST). Oxidative stress was assessed by
      determining both the production of hydrogen peroxide and by analyzing the
      activities of the antioxidative enzymes, guajacol peroxidase (POD), catalase
      (CAT), glutathione peroxidase (GPx), and the glutathione restoring enzyme
      glutathione reductase (GR). Energetic costs were evaluated by determining
      contents of fat, carbohydrates, and proteins in both exposed and control embryos.
      BL-NOM attenuated toxic effects of MC-LF and MC-RR verified by less pronounced
      teratological effects within 24 h, in particular, as well as less rise in the
      activity of s-GST, when compared with embryos exposed to either pure toxins or in
      combination with organic matter. BL-NOM also diminished oxidative effects caused
      by MC-LF; however, it failed to attenuate oxidative stress caused by MC-RR.
      Content of lipids was significantly reduced in exposed embryos following a trend
      similar to that obtained with teratological and enzymatic assays confirming the
      attenuating effect of BL-NOM. Physiological responses to microcystins and NOM
      required energetic costs, which were compensated to the expense of the energy
      resources of the yolk, which in turn might affect the normal development of
      embryos.

PMID- 16463264
TI  - Solution structure and binding specificity of FBP11/HYPA WW domain as Group
      II/III.
AB  - The Group-II/III WW domains bind Pro-rich sequences, the most frequent protein
      motif found in eucaryotic genomes. We have proposed that the Group-II and -III WW
      domains be merged into a larger group because the members of each group have
      relatively wide specificity and bind to the common ligands [Kato et al., J Biol
      Chem 2004;279:31833-31841]. We have also proposed that Group-II/III has a common
      surface patch, the XP2 groove, to bind the ligands. The first WW domain of
      FBP11/HYPA is one of the Group-II/III WW domains. The solution structure of the
      26 residue-long converged region exhibits an antiparallel triple stranded beta
      sheet with a small hydrophobic core. The WW domain of FBP11/HYPA has both XP and
      XP2 grooves on its surface. Ligand titration by 1H-15N HSQC NMR spectra revealed
      that the WW domain of FBP11/HYPA binds all the peptides with the PL, PP, and PR
      motifs. The profile patterns of chemical shift perturbation were quite similar
      among the spectra titrated with all three ligands. In addition, the titration
      significantly shifts the signals of the residues that compose the XP2 groove. All
      these findings suggest the functional importance of the XP2 groove and group
      definition of Group-II/III of the WW domains.

PMID- 16463265
TI  - Benchmarking of dimeric threading and structure refinement.
AB  - The understanding of protein-protein interactions is a major goal in the
      postgenomic era. The prediction of interaction from sequence and the subsequent
      generation of full-length dimeric models is therefore of great interest
      especially because the number of structurally characterized protein-protein
      complexes is sparse. A quality assessment of a benchmark comprised of 170 weakly
      homologous dimeric target-template pairs is presented. They are predicted in a
      two-step method, similar to the previously described MULTIPROSPECTOR algorithm:
      each target sequence is assigned to a monomeric template structure by threading;
      then, those templates that belong to the same physically interacting dimer
      template are selected. Additionally we use structural alignments as the "gold
      standard" to assess the percentage of correctly assigned monomer and dimer
      templates and to evaluate the threading results with a focus on the quality of
      the alignments in the interfacial region. This work aims to give a quantitative
      picture of the quality of dimeric threading. Except for one, all monomer
      templates are identified correctly, but approximately 40% of the dimer templates
      are still problematic or incorrect. Preliminary results for three full-length
      dimeric models generated with the TASSER method show on average a significant
      improvement of the final model over the initial template.

PMID- 16463266
TI  - Toxicity of nitrite to three species of freshwater invertebrates.
AB  - Nitrite is a compound with a high toxicity to aquatic animals. Several
      anthropogenic pollution sources are increasing the concentrations of this
      component of the nitrogen cycle. Despite this toxicity, there is little available
      literature on its effects on freshwater invertebrates. Laboratory bioassays were
      performed to obtain data on the lethal effects of nitrite to three species of
      freshwater invertebrates: the planarian Polycelis felina and the amphipods
      Echinogammarus echinosetosus and Eulimnogammarus toletanus. The LC(50), LC(10),
      and LC(0.01) values (mg/L NO(2)--N) at 24, 48, 72, and 96 h were calculated for
      each species. E. toletanus and E. echinosetosus were the most sensitive species,
      with 96 h LC(50) values of 2.09 and 2.59 mg/L NO(2)--N, respectively. In
      contrast, the planarian P. felina showed a higher tolerance to nitrite, with a 96
      h LC(50) value of 60.0 mg/L NO(2)--N. The obtained results were compared with the
      reported nitrite data for other freshwater invertebrates. This study may
      contribute to a more appropriate assessment of the ecological risk of this
      compound in freshwater ecosystems.

PMID- 16463267
TI  - Structural and thermodynamic consequences of removal of a conserved disulfide
      bond from equine beta-lactoglobulin.
AB  - A disulfide bond between cysteine 66 and cysteine 160 of equine beta
      lactoglobulin was removed by substituting cysteine residues with alanine. This
      disulfide bond is conserved across the lipocalin family. The conformation and
      stability of the disulfide-deleted mutant protein was investigated by circular
      dichroism. The mutant protein assumes a native-like structure under physiological
      conditions and assumes a helix-rich molten globule structure at acid pH or at
      moderate concentrations of urea as the wild-type protein does. The urea-induced
      unfolding experiment shows that the stability of the native conformation was
      reduced but that of the molten globule intermediate is not significantly changed
      at pH 4 by removal of the disulfide bond. On the other hand, the molten globule
      at acid pH was destabilized by removal of the disulfide bond. This difference in
      the stabilizing effect of the disulfide bond was interpreted by the effect of the
      disulfide in keeping the molecule compact against the electrostatic repulsion at
      acid pH. In contrast to the wild-type protein, the circular dichroism spectrum in
      the molten globule state at acid pH depends on anion concentration, suggesting
      that the expansion of the molecule through electrostatic repulsion induces alpha
      helices as observed in the cold denatured state of the wild-type protein.

PMID- 16463268
TI  - Differential expression of HOX genes in neoplastic and non-neoplastic human
      astrocytes.
AB  - HOX genes are a large family of regulatory genes implicated in the control of
      developmental processes. HOX genes are involved in malignant transformation and
      progression of different types of tumour. Despite intensive efforts to delineate
      the expression profiles of HOX genes in other cell types, nothing is known
      regarding the global expression profile of these genes in normal human astrocytes
      and astrocytomas. The present study has analysed the expression profile of the 39
      class I HOX genes in normal human astrocytes (NHA and E6/E7), two well
      established glioblastoma cell lines (U-87 MG and U-1242-MG), as well as
      neoplastic (WHO grades II/III and IV) and non-neoplastic temporal lobe specimens
      with hippocampal sclerosis and medically intractable epilepsy. RT-PCR,
      quantitative real-time PCR, immunocytochemistry, and western blot analyses
      revealed differential expression of nine HOX genes (A6, A7, A9, A13, B13, D4, D9,
      D10, and D13) in normal human astrocytic cell lines and non-neoplastic temporal
      lobe specimens. The data show that HOX genes are differentially expressed in
      neoplastic and non-neoplastic astrocytes and that multiple HOX genes are
      overexpressed in glioblastoma cell lines, astrocytomas (II/III), and glioblastoma
      multiforme. The differential expression of HOX genes in normal and neoplastic
      astrocytes suggests a role for these genes in brain tumourigenesis.

PMID- 16463269
TI  - STAT3 is activated in a subset of the Ewing sarcoma family of tumours.
AB  - STAT3 is an oncogene that regulates critical cellular processes and whose
      constitutive activation has been demonstrated to correlate with biological and
      clinical features in many types of human malignancy. In this study, STAT3
      activation was assessed in the Ewing sarcoma family of tumours (ESFT), which is
      characterized by fusion of the EWS gene with one of several Ets transcription
      factors, most commonly EWS-FLI1. STAT3 activation was assessed by
      immunohistochemistry using a monoclonal antibody specific for tyrosine(705)
      phosphorylated STAT3 (pSTAT3(tyr705)) and a tissue microarray containing 49
      paraffin-embedded ESFT tumours with known EWS translocations. Twenty-five (51%)
      tumours were pSTAT3(tyr705)-positive, as defined by more than 10% tumour cell
      immunostaining. STAT3 activation correlated with tumour site at presentation,
      with pSTAT3(tyr705)-negative ESFT involving axial sites predominantly (p =
      0.008). Notably, among 31 patients who presented with localized disease, high
      level STAT3 activation correlated with better overall survival (p = 0.02). STAT3
      activation was not directly related to EWS-FLI1 expression, since EWS-FLI1
      transfection did not result in STAT3 activation. Furthermore, detailed molecular
      analysis indicated that STAT3 activation may be seen with EWS-FLI1 or EWS-ERG and
      appears to be independent of EWS-FLI1 fusion type. In conclusion, STAT3
      activation is present in approximately half of ESFT and correlates with clinical
      features. The role of STAT3 activation in ESFT pathogenesis seems to be
      independent of the type of EWS/Ets translocation.

PMID- 16463270
TI  - Comparison of the immunophenotypes of signet-ring cell carcinoma, solid
      adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma
      of the lung characterized by the presence of cytoplasmic mucin.
AB  - The latest World Health Organization (WHO) classification divides adenocarcinoma
      mainly into adenocarcinoma mixed subtypes, acinar adenocarcinoma, papillary
      adenocarcinoma, bronchioloalveolar carcinoma, and solid adenocarcinoma with mucin
      production, and it mentions several variants, including fetal adenocarcinoma,
      mucinous ("colloid") adenocarcinoma, mucinous cystadenocarcinoma, signet-ring
      adenocarcinoma, and clear cell adenocarcinoma. In general, the mucin-producing
      adenocarcinoma of the lung comprises signet-ring cell carcinoma (SRCC), solid
      adenocarcinoma with mucin production (SA), and mucinous bronchioloalveolar
      carcinoma (m-BAC), mucinous ("colloid") adenocarcinomas and/or mucinous
      cystadenocarcinoma, and mucoepidermoid carcinoma. As SRCC, SA, and m-BAC exhibit
      distinct clinical features, it is important to identify differences in their
      immunohistochemical characteristics to better understand their histogenesis. In
      this study we analysed SRCC, SA, m-BAC, normal lung, and foregut-related
      secretory tissue for immunohistochemical differences using tissue microarrays.
      SRCC and SA showed high expression of MUC1 (97.4% and 100%, respectively),
      cytokeratin (CK) 7 (both 100%), and thyroid transcription factor-1 (TTF-1) (81.1%
      and 100%, respectively). They also showed low expression of MUC5AC (25.5% and
      21.1%, respectively) and MUC6 (18.3% and 10.5%, respectively), whereas m-BAC
      showed high expression of MUC5AC (97.5%), MUC6 (75.0%), and CK7 (94.7%), but low
      expression of MUC1 (57.5%), and TTF-1 (27.5%). Hierarchical clustering showed
      that the immunophenotypes of SRCC and SA belong to the same category as alveolar
      lining cells, whereas m-BAC clustered onto another branch with gastric foveolar
      cells and bronchial goblet cells. These immunohistochemical findings support the
      results of our previous clinicopathological analysis of SRCC of the lung showing
      that SRCC occurs anatomically in the peripheral portion of the lung rather than
      in the bronchial gland-bearing portion.

PMID- 16463271
TI  - Impact of oedema on recovery after major abdominal surgery and potential value of
      multifrequency bioimpedance measurements.
AB  - BACKGROUND: The consequences of generalized oedema following major abdominal
      surgery are under-recognized, and its causes are poorly understood. METHODS:
      Thirty-eight patients (21 men and 17 women) were observed for the occurrence of
      oedema after major abdominal surgery. Oedema formation was related to fluid
      balance, changes in whole-body bioimpedance (Z) measured at four frequencies (5,
      50, 100 and 200 kHz), and clinical outcome. RESULTS: The 20 patients who
      developed oedema were older than those who did not (mean(s.d.) 73(9) versus
      63(14) years; P = 0.007). Fluid intake over the first 5 days after surgery was
      similar in both groups, but those with oedema excreted less total fluid
      (16.9(2.4) versus 19.7(3.5) litres; P = 0.022). Oedema was associated with a
      delay in tolerating solid food (P = 0.001) and opening bowels (P = 0.020), a
      prolonged hospital stay (median 17 (range 8-59) versus 9 (range 4-27) days; P =
      0.001) and more postoperative complications (13 of 20 versus four of 18 patients;
      P = 0.011). The preoperative ratio of whole-body impedance at 200 kHz to that at
      5 kHz was higher in those who subsequently developed oedema (0.81(0.03) versus
      0.78(0.02); P = 0.015). CONCLUSION: The development of oedema after major
      abdominal surgery is associated with increased morbidity. Age and reduced ability
      to excrete administered fluid load are significant aetiological factors and
      bioimpedance analysis can potentially identify patients at risk.

PMID- 16463272
TI  - Teratology Public Affairs Committee position paper: maternal obesity and
      pregnancy.
AB  - Compared to normal-weight women, obese women have an increased risk of
      infertility and pregnancy complications. The most consistently described
      pregnancy complications are hypertensive disorders, gestational diabetes
      mellitus, thromboembolic events, and cesarean section. Fetal and neonatal
      complications may include congenital malformations, macrosomia, and shoulder
      dystocia. The literature suggests that women with a body mass index (BMI) >or=30
      have approximately double the risk of having a child with a neural tube defect
      (NTD) compared to normal-weight women, and the increased risk associated with
      higher maternal body weight does not appear to be modified by folic acid
      supplementation. The Public Affairs Committee of the Teratology Society supports
      the public health initiatives identified by the U.S. Food and Drug Administration
      in 2004 and the research initiatives identified by the National Institutes of
      Health in 2004. The Public Affairs Committee recommends that clinicians counsel
      women about appropriate caloric intake and exercise and that health-care
      providers educate parents about appropriate childhood nutrition. Breast-feeding
      should be encouraged based on evidence of a protective effect against childhood
      obesity, as well as other health advantages.

PMID- 16463273
TI  - Linking teratogen information service and birth defects registry databases to
      improve knowledge of birth defect status.
AB  - BACKGROUND: Although teratogen information services (TISs) obtain maternal
      exposure information from their callers, such services often do not know if the
      pregnancies were affected by a birth defect. This study attempted to improve the
      completeness of this information for Texas Teratogen Information Service (TTIS)
      callers by linking their records with the Texas Birth Defects Registry (TBDR) and
      Texas birth certificates (TBCs). METHODS: A total of 344 expectant mothers called
      TTIS with expected dates of delivery between 1 January 2000 and 31 December 2001.
      These pregnancies were linked with TBDR and TBC data. The percentages of
      pregnancies with known birth defect information both before and after the linkage
      were compared. RESULTS: The TTIS originally collected birth defect status
      information for 101 of the 344 callers (29.4%) and 0.6% of all 344 callers or
      2.0% of callers with birth defect status information had a pregnancy affected by
      a birth defect. Linking TTIS records with TBDR and TBC data helped to raise the
      percentage of callers with birth defect status information from 29.4% to 71.5%.
      Among those callers, the percentage known to have birth defects increased from
      2.0% to 4.1%. The sensitivity of TTIS follow-up calls in identifying birth
      defects was 50%, and the specificity was 100%. CONCLUSIONS: Linking TTIS caller
      records with TBDR and TBC data significantly increased both the percentage of
      pregnancies with birth defect status information and the percentage of
      pregnancies identified as affected by birth defects. Such linkage may be a good
      approach by which TISs can increase the completeness of their birth defect status
      information.

PMID- 16463274
TI  - AGTR2 in brain development and function.

PMID- 16463275
TI  - Role of leptin in regulating appetite, neuroendocrine function, and bone
      remodeling.
AB  - Leptin, a hormone secreted by adipocytes, acts on the hypothalamus to regulate
      appetite and neuroendocrine function. In the hypothalamus, both the arcuate
      nucleus and the ventromedial nucleus express leptin receptors. Specific neurons
      in the arcuate nucleus regulate appetite and reproduction. In contrast, neurons
      in the ventromedial nucleus regulate bone mass. The melanocortin system is the
      downstream pathway for regulating appetite and neuroendocrine function. In
      contrast, the sympathetic nervous system is the downstream pathway for regulating
      bone mass. Leptin, in regulating food intake and body weight, acts, in part, by
      inhibiting the synthesis of neuropeptide Y and its release from the hypothalamus.
      The leptin and insulin pathways may interact and may be important in the
      pathogenesis of the metabolic syndrome.

PMID- 16463276
TI  - Functional evolution within a protein superfamily.
AB  - The ability to predict and characterize distributions of reactivities over
      families and even superfamilies of proteins opens the door to an array of
      analyses regarding functional evolution. In this article, insights into
      functional evolution in the Kazal inhibitor superfamily are gained by analyzing
      and comparing predicted association free energy distributions against six serine
      proteinases, over a number of groups of inhibitors: all possible Kazal
      inhibitors, natural avian ovomucoid first and third domains, and sets of Kazal
      inhibitors with statistically weighted combinations of residues. The results
      indicate that, despite the great hypervariability of residues in the 10
      proteinase-binding positions, avian ovomucoid third domains evolved to inhibit
      enzymes similar to the six enzymes selected, whereas the orthologous first
      domains are not inhibitors of these enzymes on purpose. Hypervariability arises
      because of similarity in energetic contribution from multiple residue types;
      conservation is in terms of functionality, with "good" residues, which make
      positive or less deleterious contributions to the binding, selected more
      frequently, and yielding overall the same distributional characteristics. Further
      analysis of the distributions indicates that while nature did optimize inhibitor
      strength, the objective may not have been the strongest possible inhibitor
      against one enzyme but rather an inhibitor that is relatively strong against a
      number of enzymes.

PMID- 16463277
TI  - Control of neurite outgrowth and growth cone motility by phosphatidylinositol-3
      kinase.
AB  - Phosphatidylinositol-3-kinase (PI-3K) has been reported to affect neurite
      outgrowth both in vivo and in vitro. Here we investigated the signaling pathways
      by which PI-3K affects neurite outgrowth and growth cone motility in identified
      snail neurons in vitro. Inhibition of PI-3K with wortmannin (2 microM) or LY
      294002 (25 microM) resulted in a significant elongation of filopodia and in a
      slow-down of neurite outgrowth. Experiments using cytochalasin and blebbistatin,
      drugs that interfere with actin polymerization and myosin II activity,
      respectively, demonstrated that filopodial elongation resulting from PI-3K
      inhibition was dependent on actin polymerization. Inhibition of strategic kinases
      located downstream of PI-3K, such as Akt, ROCK, and MEK, also caused significant
      filopodial elongation and a slow-down in neurite outgrowth. Another growth cone
      parameter, filopodial number, was not affected by inhibition of PI-3K, Akt, ROCK,
      or MEK. A detailed study of growth cone behavior showed that the filopodial
      elongation induced by inhibiting PI-3K, Akt, ROCK, and MEK was achieved by
      increasing two motility parameters: the rate with which filopodia extend
      (extension rate) and the time that filopodia spend elongating. Whereas the
      inhibition of ROCK or Akt (both activated by the lipid kinase activity of PI-3K)
      and MEK (activated by the protein kinase activity of PI-3K) had additive effects,
      simultaneous inhibition of Akt and ROCK showed no additive effect. We further
      demonstrate that the effects on filopodial dynamics investigated were calcium
      independent. Taken together, our results suggest that inhibition of PI-3K
      signaling results in filopodial elongation and a slow-down of neurite advance,
      reminiscent of growth cone searching behavior.

PMID- 16463278
TI  - Predicting the three-dimensional structure of human P-glycoprotein in absence of
      ATP by computational techniques embodying crosslinking data: insight into the
      mechanism of ligand migration and binding sites.
AB  - P-glycoprotein is a membrane protein involved in the phenomenon of multidrug
      resistance. Its activity and transport function have been largely characterized
      by various biochemical studies and a low-resolution image has been obtained by
      electron microscopy. Obtaining a high-resolution structure is, however, still
      remote due to the inherent difficulties in the experimental determination of
      membrane protein structures. We present here a three-dimensional (3D) atomic
      model of P-glycoprotein in absence of ATP. This model was obtained using a
      combination of computational techniques including comparative modeling and rigid
      body dynamics simulations that embody all available cysteine disulfide
      crosslinking data characterizing the whole protein in absence of ATP. The model
      features rather well most of the experimental interresidue distances derived both
      in the transmembrane domains and in the nucleotide binding domains. The model is
      also in good agreement with electron microscopy data, particularly in terms of
      size and topology. It features a large cavity detected in the protein core into
      which seven ligands were successfully docked. Their predicted affinity correlates
      well with experimental values. Locations of docked ligands compare favorably with
      those suggested by cysteine-scanning data. The finding of different positions
      both for a single ligand and for different ligands corroborates the experimental
      evidence indicating the existence of multiple drug binding sites. The
      interactions identified between P-glycoprotein and the docked ligands reveal that
      different types of interactions such as H-bonds, pi-pi and cation-pi interactions
      occur in agreement with a recently proposed pharmacophore model of P-glycoprotein
      ligands. Furthermore, the model also displays a lateral opening located in the
      transmembrane domains connecting the lipid bilayer to the central cavity. This
      feature supports rather well the commonly admitted mechanism of substrate uptake
      from the lipid bilayer. We propose that this 3D model may be an important tool to
      understand the structure-function relationship of P-glycoprotein.

PMID- 16463279
TI  - Low density lipoprotein receptor-related protein-2/megalin is expressed in
      oligodendrocytes in the mouse spinal cord white matter.
AB  - Lipoprotein receptor-related protein-2 (LRP2)/megalin is a member of the low
      density lipoprotein receptor (LDLR) family, and is essential in absorptive
      epithelia for endocytosis of lipoproteins, low molecular weight proteins,
      cholesterol and vitamins, as well as in cellular signaling. Previous studies have
      shown megalin expression in ependymal cells and choroid plexus. We have
      investigated megalin expression in the spinal cord of postnatal mice with
      immunohistochemistry and immunoblot. Antibodies recognizing either the
      cytoplasmic tail (MM6) or the extracellular domain (E11) of megalin labeled
      oligodendrocytes in the spinal cord white matter, in parallel with myelination.
      MM6 antibodies, predominantly labeled the nuclei, whereas E11 antibodies labeled
      the cytoplasm of these cells. MM6 antibodies labeled also nuclei of
      oligodendrocytes cultured from embryonic mouse spinal cord. Immunoblots of spinal
      cord showed intact megalin, as well as its carboxyterminal fragment, the part
      remaining after shedding of the extracellular domain of megalin. Megalin
      immunoreactive oligodendrocytes also expressed presenilin 1, an enzyme
      responsible for gamma-secretase mediated endodomain cleavage. These findings show
      that spinal cord oligodendrocytes are phenotypically different from those in the
      brain, and indicate that megalin translocates signals from the cell membrane to
      the nucleus of oligodendrocytes during the formation and maintenance of myelin of
      long spinal cord pathways.

PMID- 16463280
TI  - Open brain gene product Rab23: expression pattern in the adult mouse brain and
      functional characterization.
AB  - The gene mutated in the mouse open brain (opb) phenotype antagonizes sonic
      hedgehog-mediated signaling and encodes a small GTPase of the Rab family, Rab23.
      To date, the brain expression profile and exact mechanism of function of the
      Rab23 protein has remained unknown. Specific antibodies generated against Rab23
      showed that the protein is highly enriched in the adult rodent brain and present
      in low levels in multiple tissues of the adult rodent. Rab23 is found in the
      cytosol as well as being associated with the plasma and endosomal membranes. In
      the adult mouse brain, Rab23 is found in betaIII tubulin (TuJ) positive neuronal
      cell bodies and are most prominent in the cortex, hypothalamus and the
      cerebellum. It is, however, absent from glial fibrillary acidic protein (GFAP)
      positive astrocytes or CNPase positive oligodendrocytes. Despite the plasma
      membrane/endosomal membrane localization of Rab23, neither overexpression of the
      GTP-restricted nor the GDP-bound mutant forms affect internalization of
      transferrin or epidermal growth factor. Exogenous overexpression of Rab23 or its
      mutants also did not affect the morphological differentiation of thalamic neurons
      in culture. Expression of Rab23 in the adult brain is suggestive, however, of
      having a postnatal function beyond its role in embryonic development.

PMID- 16463281
TI  - Mass spectrometry and natural variations of iron isotopes.
AB  - Although the processes that govern iron isotope variations in nature are just
      beginning to be understood, multiple studies attest of the virtue of this system
      to solve important problems in geosciences and biology. In this article, we
      review recent advances in the geochemistry, cosmochemistry, and biochemistry of
      iron isotopes. In Section 2, we briefly address the question of the
      nucleosynthesis of Fe isotopes. In Section 3, we describe the different methods
      for purifying Fe and analyzing its isotopic composition. The methods of SIMS,
      RIMS, and TIMS are presented but more weight is given to measurements by MC
      ICPMS. In Section 4, the isotope anomalies measured in extraterrestrial material
      are briefly discussed. In Section 5, we show how high temperature processes like
      evaporation, condensation, diffusion, reduction, and phase partitioning can
      affect Fe isotopic composition. In Section 6, the various low temperature
      processes causing Fe isotopic fractionation are presented. These involve aqueous
      and biologic systems.

PMID- 16463282
TI  - Investigation of molecular interaction within biological macromolecular complexes
      by mass spectrometry.
AB  - The advent of electrospray ionization (ESI) and matrix-assisted laser desorption
      ionization (MALDI) has accelerated structural studies of biological
      macromolecular complexes. At present, mass spectrometry can provide accurate mass
      values not only of individual biological macromolecules but also of their
      assemblies. Furthermore, it can also give information on the interface sites of
      the biological macromolecular complexes. The present article focuses on the role
      of mass spectrometry in the investigation of biological molecular interactions,
      such as protein-protein, protein-DNA, and protein-ligand interactions, which play
      essential roles in various biological events.

PMID- 16463283
TI  - Processing and classification of protein mass spectra.
AB  - Among the many applications of mass spectrometry, biomarker pattern discovery
      from protein mass spectra has aroused considerable interest in the past few
      years. While research efforts have raised hopes of early and less invasive
      diagnosis, they have also brought to light the many issues to be tackled before
      mass-spectra-based proteomic patterns become routine clinical tools. Known issues
      cover the entire pipeline leading from sample collection through mass
      spectrometry analytics to biomarker pattern extraction, validation, and
      interpretation. This study focuses on the data-analytical phase, which takes as
      input mass spectra of biological specimens and discovers patterns of peak masses
      and intensities that discriminate between different pathological states. We
      survey current work and investigate computational issues concerning the different
      stages of the knowledge discovery process: exploratory analysis, quality control,
      and diverse transforms of mass spectra, followed by further dimensionality
      reduction, classification, and model evaluation. We conclude after a brief
      discussion of the critical biomedical task of analyzing discovered discriminatory
      patterns to identify their component proteins as well as interpret and validate
      their biological implications.

PMID- 16463285
TI  - A molecular actinide-tellurium bond and comparison of bonding in
      [M(III){N(TePiPr2)2}3] (M=U, La).

PMID- 16463286
TI  - Exploring two-state reaction pathways in the photodimerization of cyclohexadiene.
AB  - The ground- (S0) and lowest triplet-state (T1) pathways associated with
      dimerization of cyclohexadiene to give [2+2] and [4+2] cycloadducts have been
      theoretically studied at the UBLYP and UB3LYP levels of theory with the 6-31G*
      basis set. The DFT energies were validated by CCSD(T) single-point energy
      calculations. These cycloaddition reactions follow stepwise mechanisms with
      formation of bis-allylic biradical (BB) intermediates. In the S0 ground state,
      the interaction between two cyclohexadiene molecules with formation of BB
      intermediate IN(S0) has a large activation enthalpy of 32.0 kcal mol(-1). On the
      other hand, C-C bond-formation in the lowest triplet state (T1) leading to BB
      intermediate IN(T1) has a low activation enthalpy of 5.0 kcal mol(-1), but the
      subsequent ring closure involves a very large activation enthalpy of 43.4 kcal
      mol(-1). Triplet-to-singlet intersystem crossing from IN(T1) to IN(S0) favors
      cyclization to give the corresponding [2+2] and [4+2] cycloadducts.

PMID- 16463284
TI  - Molecular diversity of Glanzmann thrombasthenia in southern India: new insights
      into mRNA splicing and structure-function correlations of alphaIIbbeta3 integrin
      (ITGA2B, ITGB3).
AB  - The molecular basis of Glanzmann thrombasthenia (GT) was studied in 40 families
      from southern India. Of 23 identified mutations (13 in the alphaIIb (ITGA2B) gene
      and 10 in the beta3 (ITGB3) gene), 20 were novel and three were described
      previously. Three mutations in the beta3 gene-p.Leu143Trp (Leu117Trp),
      p.Tyr307Stop (Tyr281Stop), and p.Arg119Gln (Arg93Gln)-were detected in 12, three,
      and two families, respectively, with definite founder effects observed for the
      first two mutations. Alternative splicing was predicted in silico for the normal
      variant and a missense variant of the beta3 gene, and for 10/11 frameshift or
      nonsense mutations in alphaIIb or beta3. The prediction was confirmed
      experimentally for a c.2898_2902dupCCCCT mutation in exon 28 of the alphaIIb gene
      that induced exon skipping. Seven out of nine missense mutations substituted
      highly conserved amino acids buried in the proteins' cores, predicting structural
      abnormalities. Among these, a beta3 substitution, p.Cys39Gly (Cys13Gly) was found
      to cause intracellular degradation of the beta3 subunit, in contrast to previous
      findings that mutations at Cys435, the partner of Cys13 in a disulfide bond,
      cause constitutive activation of alphaIIbbeta3. The two patients with a beta3
      Arg93Gln mutation had normal clot retraction, consistent with a recent finding
      that this substitution is associated with normal surface expression of
      alphaIIbbeta3. In conclusion, this study demonstrates that a variety of mutations
      account for GT in southern Indian patients, provides new insights into mRNA
      splicing, and highlights the role of specific amino acids in structure-function
      correlations of alphaIIbbeta3.

PMID- 16463288
TI  - Maternal serum alpha-fetoprotein, fetal middle cerebral artery blood flow
      velocity and fetal haemoglobin in pregnancies at risk of fetal anaemia.
AB  - OBJECTIVES: To evaluate the relationships between maternal serum alpha
      fetoprotein (MSAFP) levels and both middle cerebral artery (MCA) peak systolic
      velocity and fetal haemoglobin in women at risk of fetal anaemia. METHODS: Forty
      one measurements of MSAFP were carried out in 22 women at risk of fetal anaemia
      (16 alloimmunised patients and 6 cases of parvovirus infection) who were
      monitored by using MCA Doppler measurements. The relationships between MSAFP
      (MoM) and both MCA peak systolic velocity (z-scores) and fetal haemoglobin (MoM)
      were studied. RESULTS: There were significant correlations between MSAFP and both
      MCA Doppler measurements (r = 0.56, p = 0.00017) and fetal haemoglobin (n = 13, r
      = -0.71, p = 0.006). MSAFP was higher in cases with fetal anaemia (n = 10) than
      in those with normal haemoglobin levels (n = 3) (1.7 +/- 0.4 vs 0.8 +/- 0.1 MoM;
      p = 0.006). In cases of alloimmunised pregnancies with fetal anaemia, MSAFP
      elevations preceded the presence of increased MCA Doppler velocity by 2.7 weeks
      (range 0-9 weeks). CONCLUSION: MSAFP is significantly correlated with both MCA
      Doppler measurements and fetal haemoglobin. Elevations of MSAFP may appear
      earlier than MCA Doppler abnormalities in cases of fetal anaemia associated with
      red blood cell alloimmunisation.

PMID- 16463289
TI  - Women's opinions on the offer and use of nuchal translucency screening for Down
      syndrome.
AB  - OBJECTIVE: To study the attitude of Dutch women to the offer and subsequent
      (non)use of nuchal translucency (NT) screening for Down syndrome in the first
      trimester of pregnancy, in a country where screening is not routinely offered
      under 36 years of age. METHODS: An experimental NT screening programme offered to
      pregnant women, together with a series of questionnaires to be completed before
      and after the offer and (non)use of screening, in 12 midwife practices in three
      different health districts. PARTICIPANTS: Cohort of pregnant women who had their
      first prenatal care visit in the participating midwife practices between 1 June
      1999 and 1 January 2001. MAIN OUTCOME MEASURES: Women's knowledge and
      understanding of prenatal screening tests; attitude towards screening offer;
      perceived freedom of choice; satisfaction with information given; change in
      attitude over time. RESULTS: Eighty-six percent of women accepted the offer of NT
      screening. Seventy percent had previous knowledge of NT screening and 92%
      considered the information given before screening clear and sufficient. Thirty
      nine percent of women felt worried to some extent after being given the
      information, but only 3% would have preferred not to have been informed at all.
      Ninety percent of women (including 68% of decliners) agree that information on
      Down syndrome screening should be extended to all pregnant women and feel
      competent in deciding on screening participation. CONCLUSION: When NT screening
      is offered as a new screening strategy its concept is understood and well
      accepted. The large majority of women, including the decliners, are in favour of
      its standard offer.

PMID- 16463290
TI  - Ultrasonographic evaluation of fetal nasal bone in a low-risk population at 11-13
      + 6 gestational weeks.
AB  - OBJECTIVE: To evaluate the utility of determining the presence/absence of nasal
      bone in a low-risk fetal population. METHODS: Prospective study of the
      presence/absence of nasal bone among 1800 consecutive unselected fetuses, with
      complete follow-up of results. RESULTS: An adequate sonographic evaluation of
      nasal bone was obtained in 1682 (93.44%) of the fetuses. Nasal bone was
      considered absent in 19 (1.06%) of 1790 fetuses with a normal karyotype and in 2
      (28.57%) of the seven recorded cases of Down syndrome (DS). The overall first
      trimester sensitivity for DS to the absence of nasal bone was two of the six
      cases (33.3%) and the false-positive rate was 1.13%. The positive predictive
      value for DS of the absence of nasal bone was 2/21 (9.52%). CONCLUSIONS: In a low
      risk population, the evaluation of the presence/absence of nasal bone in DS
      screening during the first trimester has a low sensitivity. First-trimester
      assessment of the nasal bone in population screening may play a lesser role than
      in the re-evaluation of high-risk pregnancies.

PMID- 16463291
TI  - De novo chromosomal abnormalities and month of conception.
AB  - OBJECTIVES: We set out to study the possible relationship between the occurrence
      of chromosomal abnormalities and the month of conception using data from 7 years
      of prenatal diagnosis. METHODS: The sample included 7439 cytogenetic analyses
      from amniocentesis performed for conceptions between 1997 and 2003. The monthly
      prevalence of all de novo chromosomal abnormalities, trisomies, including trisomy
      21, and Robertsonian translocations was investigated. RESULTS: Two hundred and
      four de novo numerical and structural chromosomal abnormalities (2.7%) were
      detected. A significant decrease in the frequencies of all de novo chromosomal
      abnormalities for June conceptions, as well as lower summer occurrences of
      trisomy 21, were found. In addition, de novo Robertsonian translocations were
      unexpectedly detected only among December conceptions. CONCLUSIONS: The
      relationship between chromosomal abnormalities and the month of conception could
      turn out to be useful in estimating the actual risk in pregnancy, if confirmed by
      other studies. The observed June lowest rate might indicate an association
      between chromosomal abnormalities and the maximum number of daylight hours
      throughout the year (summer solstice). We cannot explain the unusual findings
      concerning Robertsonian translocations that were only found for conceptions in
      December. This may be related to the annual minimum daylight hours (winter
      solstice) as opposed to the summer solstice.

PMID- 16463292
TI  - Forty-eight-hour first-trimester glucose profiles in women with type 1 diabetes
      mellitus: a report of three cases of congenital malformation.
AB  - OBJECTIVE: Despite modern methods of treatment and near-normal HbA(1c) levels,
      women with type 1 diabetes mellitus are still at risk of having an infant with a
      congenital malformation (CM). We hypothesised that HbA(1c) levels are too gross a
      measure of glycaemic control and used a continuous glucose monitoring system
      (CGMS) to determine the diurnal glucose profiles during the first trimester of
      pregnancy. We present three cases of infants with a CM. METHODS: Fifty-three
      women with type 1 diabetes used the CGMS for 48 h in the first trimester of
      pregnancy. Three of them gave birth to infants with a CM. HbA(1c) levels were
      determined at the time of the CGMS measurement and 6 to 8 weeks later. RESULTS:
      The HbA(1c) levels at the time of the CGMS measurement were 6.0, 6.5 and 7.8%
      (normal range 4.0-6.0%) in the three women. The 48-h diurnal glucose profiles of
      these women showed a large variability with frequent hyperglycaemic episodes.
      CONCLUSIONS: HbA(1c) levels are too gross a measure of glycaemic control to
      identify women at risk of giving birth to an infant with a CM. Even in women with
      normal or near-normal HbA(1c) levels, the diurnal glucose profiles reveal
      intermittent hyperglycaemic episodes that may cause the CM.

PMID- 16463293
TI  - Natural history of prenatally diagnosed 46,X,isodicentric Y.
AB  - OBJECTIVES: The karyotype 46,X,isodicentric Y has rarely been reported in the
      context of prenatal diagnosis. The literature is replete with descriptions of
      individuals with 46,X,isodicentric Y/45,X mosaicism, presenting with a spectrum
      of phenotypes. The postnatal phenotype is believed to depend on the extent of
      mosaicism in the gonads or other affected tissues. The purpose of this article is
      to delineate the natural history of this chromosomal abnormality when identified
      in the context of prenatal diagnosis. METHODS: We identified a 45,X/46,X,idicY
      karyotype in the structurally normal male fetus of a woman presenting with an
      abnormal triple screen. Four other prenatally ascertained cases were found in our
      files as well as ten in the medical literature. RESULTS: Of the 15 cases
      presented here, 11 (73%) were reported as phenotypically normal males, 1 was
      found to have an epididymal cyst, and 1 had normal male genitalia, but was also
      found to have a cardiovascular defect. One out of 15 (7%) was found to have
      female genitalia and was therefore confirmed to have Turner syndrome. In one
      case, the outcome was not reported. CONCLUSION: An individual diagnosed
      prenatally with idic(Y) may in many cases be a normal male, similar to the
      outcome for prenatally diagnosed 45,X/46,XY.

PMID- 16463294
TI  - Prenatal diagnosis of an exceptional intrauterine herpes simplex type 1
      infection.
AB  - OBJECTIVE: To assess ultrasound findings of a fetus with intrauterine growth
      retardation (IUGR) and skin damage, related to intrauterine herpes simplex virus
      (HSV) infection. METHODS: A 23-year-old, G1, P0 woman was referred at 23.5 weeks'
      gestation (WG) for IUGR. The patient had a previous single episode of serotype 1
      herpes progenitalis at 11 WG. Ultrasound examination revealed extensive skin
      changes with no cerebral involvement. The methods employed for evaluation of the
      disease included maternal serology, amniocentesis and repeated ultrasound
      examinations. RESULTS: Maternal serology was positive for HSV1 and fetal
      infection was confirmed via polymerase chain reaction (PCR). At 27 WG, amniotic
      fluid index decreased and lower limb skin as well as abdominal skin was
      irregular. Oesophagus was thickened. In contrast, upper limb skin and cranial
      vault were thin and less visible. IUGR was predominant as regards bone
      parameters. After termination of pregnancy, the fetus showed macroscopic
      characteristics of HSV infection. Microscopic examination revealed only placental
      and skin lesions. CONCLUSIONS: Our report illustrates a rare case of HSV1
      intrauterine infection that occurred during the first trimester with bone and
      cephalic IUGR associated with extensive skin damage, and with no cerebral
      involvement.

PMID- 16463295
TI  - Mid-facial anthropometry in second-trimester fetuses with trisomy 21: a three
      dimensional ultrasound study.
AB  - OBJECTIVES: The aim of this study was to evaluate whether fetuses with trisomy 21
      and detectable nasal bones have a distinct facial anthropometry that can be
      objectively defined using three-dimensional (3D) ultrasonography. METHODS: A
      prospective cross-sectional study of 40 fetuses in the second trimester, 17 with
      trisomy 21 and 23 controls, was performed. The 3D volume datasets of each case
      were evaluated for documentation of the nasal bones using the multiplanar and the
      maximum mode. The nasal bone length and the angle formed by the two maxillary
      bones at the level of the frontal process were then measured. RESULTS: The nasal
      bones were absent in 7 (41%) of the 17 fetuses with Down syndrome. All of the 23
      normal fetuses had detectable nasal bones. The difference between nasal bone
      length in trisomy 21 fetuses and controls did not reach statistical significance
      (p = 0.087). The mean maxillary angle in trisomy 21 fetuses with nasal bones was
      significantly wider compared to controls (p = 0.029). CONCLUSIONS: The nasal
      bones are present in the majority of fetuses with trisomy 21 in the second
      trimester. This group of fetuses has a characteristic mid-facial anthropometry
      (wider maxillary angle) that can be assessed by means of 3D ultrasonography.

PMID- 16463296
TI  - Mirror syndrome due to parvovirus B19 hydrops complicated by severe maternal
      pulmonary effusion.

PMID- 16463297
TI  - Homozygous alpha-thalassemia associated with micropenis in a fetus.

PMID- 16463298
TI  - Investigation of proton density for measuring tissue temperature.
AB  - PURPOSE: To examine the temperature dependence of the proton density (PD) in both
      adipose and muscle tissues, and the application of the PD as a thermometry
      parameter in breast tissues. MATERIALS AND METHODS: Porcine fat samples and
      bovine muscle samples were successively heated to temperatures ranging from 30
      degrees C to 76 degrees C and then cooled. They were then imaged with a dual-echo
      spin-echo sequence. T1 and T2 effects were carefully corrected from the images.
      The apparent PD (APD) in regions of interest (ROIs) and the sum of the APD in all
      pixels (Sum_APD) were measured and analyzed by linear regression. RESULTS: APD in
      adipose tissue is linear and reversible, and changes with a 0.3%/ degrees C to
      0.45%/ degrees C temperature variation. The temperature coefficient of Sum_APD in
      adipose tissue is approximately 0.29%/ degrees C, as predicted from the Boltzmann
      distribution. However, the results in muscle tissue are more variable. There is
      an offset in both APD and Sum_APD between heating and cooling phases, as well as
      different temperature coefficients between these two phases. CONCLUSION: The
      Sum_APD in adipose tissue validates the 1/T dependence on temperature. The APD is
      a potentially useful parameter for fat thermometry; however, its application in
      muscle tissue requires further investigation.

PMID- 16463299
TI  - Quantitative myocardial perfusion analysis with a dual-bolus contrast-enhanced
      first-pass MRI technique in humans.
AB  - PURPOSE: To compare fully quantitative and semiquantitative analysis of rest and
      stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using a
      dual-bolus first-pass perfusion MRI method in humans. MATERIALS AND METHODS: Rest
      and dipyridamole stress perfusion imaging was performed on 10 healthy humans by
      administering gadolinium contrast using a dual-bolus protocol. Ventricular and
      myocardial time-signal intensity curves were generated from a series of T1
      weighted images and adjusted for surface-coil intensity variations. Corrected
      signal intensity curves were then fitted using fully quantitative model
      constrained deconvolution (MCD) to quantify MBF (mL/min/g) and MPR. The results
      were compared with semiquantitative contrast enhancement ratio (CER) and upslope
      index (SLP) measurements. RESULTS: MBF (mL/min/g) estimated with MCD averaged
      1.02 +/- 0.22 at rest and 3.39 +/- 0.59 for stress with no overlap in measures.
      MPR was 3.43 +/- 0.71, 1.91 +/- 0.65, and 1.16 +/- 0.19 using MCD, SLP, and CER.
      Both semiquantitative parameters (SLP and CER) significantly underestimated MPR
      (P < 0.001) and failed to completely discriminate rest and stress perfusion.
      CONCLUSION: Rest and stress MBF (mL/min/g) and MPR estimated by dual-bolus
      perfusion MRI fit within published ranges. Semiquantitative methods (SLP and CER)
      significantly underestimated MPR.

PMID- 16463300
TI  - Pulsed arterial spin labeling parameter optimization for an elderly population.
AB  - PURPOSE: To optimize pulsed arterial spin labeling (PASL) parameters for the
      elderly to take into account possible perfusion changes that occur in the brain
      with age. MATERIALS AND METHODS: Healthy young (N = 14, age range = 21-27 years)
      and elderly (N = 12, age range = 61-67 years) subjects were scanned using Q2TIPS
      (QUIPSS II with thin-slice TI, periodic saturation) with varying inversion times
      (TI(2)) at 1.5T. The difference signal (DeltaM), transit time (deltat), and
      cerebral blood flow (CBF) were calculated in segmented gray matter (GM). RESULTS:
      The young displayed more perfusion-weighted signal difference than the elderly at
      all TI(2)'s. The peak DeltaM occurred at TI(2) approximately 1300 msec and 1500
      msec in the young and elderly groups, respectively. Qualitatively, intravascular
      signal was minimal in the younger group by TI(2) = 1500 msec, whereas a longer
      TI(2) of 1800 msec was needed to minimize this signal in the elderly. The transit
      time was approximately 100 msec longer in the elderly, and CBF was in the range
      of literature values. CONCLUSION: For acquiring perfusion-weighted images with
      minimal intravascular signal and adequate tissue signal for PASL studies of
      cerebral perfusion in the elderly, a longer inversion time is advantageous.

PMID- 16463301
TI  - Magnetic resonance brain perfusion imaging with voxel-specific arterial input
      functions.
AB  - PURPOSE: To propose an automatic method for estimating voxel-specific arterial
      input functions (AIFs) in dynamic contrast brain perfusion imaging. MATERIALS AND
      METHODS: Voxel-specific AIFs were estimated blindly using the theory of
      homomorphic transformations and complex cepstrum analysis. Wiener filtering was
      used in the subsequent deconvolution. The method was verified using simulated
      data and evaluated in 10 healthy adults. RESULTS: Computer simulations accurately
      estimated differently shaped, normalized AIFs. Simple Wiener filtering resulted
      in underestimation of flow values. Preliminary in vivo results showed comparable
      cerebral flow value ratios between gray matter (GM) and white matter (WM) when
      using blindly estimated voxel-specific AIFs or a single manually selected AIF.
      Significant differences (P < or = 0.0125) in mean transit time (MTT) and time-to
      peak (TTP) in GM compared to WM was seen with the new method. CONCLUSION: Initial
      results suggest that the proposed method can replace the tedious and difficult
      task of manually selecting an AIF, while simultaneously providing better
      differentiation between time-dependent hemodynamic parameters.

PMID- 16463302
TI  - Gastric motor function and emptying in the right decubitus and seated body
      position as assessed by magnetic resonance imaging.
AB  - PURPOSE: To determine the effect of the right decubitus lying body position (RP)
      on relevant parameters of human gastric motor function in healthy volunteers.
      MATERIALS AND METHODS: Postprandial gastric function after ingestion of a
      solid/liquid meal (150 g/150 mL) was assessed over 90 minutes in volunteers in
      the RP and seated position (SP). Ten healthy volunteers were imaged using two MRI
      systems that differed in architecture and field strength. Stomach and
      intragastric air volume, intragastric meal distribution, gastric emptying, and
      gastric peristalsis were compared between the RP and SP. RESULTS: Body position
      did not affect gastric relaxation (RP, 372 mL vs. SP, 384 mL) and initial gastric
      volumes (stomach: RP, 458 mL vs. SP, 462 mL; meal: RP, 377 mL vs. SP, 399 mL;
      intragastric air: RP, 110 mL vs. SP, 98 mL). Postprandial stomach volume and
      gastric activity (RP and SP, 3.1 minute(-1)) were also similar. Meal emptying
      showed different characteristics, resulting in a significant but small difference
      in meal volume of -43 mL at t = 90 minutes (P < 0.05). CONCLUSION: Gastric MRI in
      RP is feasible for clinical research assessing gastric motor function. The subtle
      difference in meal emptying may be induced by posture-dependent vagal activity.
      This study confirms that MRI is a highly sensitive imaging technique for
      assessing gastrointestinal function in humans.

PMID- 16463303
TI  - Acute neurobehavioral effects of exposure to static magnetic fields: analyses of
      exposure-response relations.
AB  - PURPOSE: To assess exposure-response relations between exposure to magnetic
      fields and neurobehavioral effects. MATERIALS AND METHODS: Twenty company
      volunteers completed a neurobehavioral test battery after they moved their heads
      with the magnetic field absent, and while they moved their heads in the
      inhomogenous stray fields of 1.5 and 3.0 T MRI magnets. RESULTS: The value of the
      stray fields at the position of the head of the volunteer was estimated to be 0.6
      T and 1.0 T on the 1.5 T and 3.0 T systems, respectively. Exposure-response
      relations were found for visual (-2.1%/100 mT) and auditory (-1.0%/100 mT)
      working memory, eye-hand coordination speed (-1.0%/100 mT), and visual tracking
      tasks (-3.1%/100 mT). Eye-hand precision, scanning speed, and visual contrast
      sensitivity were apparently not influenced by the magnetic field strength.
      CONCLUSION: Additional research should focus on the potential side effects of
      interventional MR procedures because of the exposure to strong magnetic fields of
      these systems.

PMID- 16463304
TI  - Superficial femoral artery occlusive disease severity correlates with MR cine
      phase-contrast flow measurements.
AB  - PURPOSE: To evaluate how cine phase-contrast (PC) flow data correlate with the
      severity of peripheral vascular disease (PVD). MATERIALS AND METHODS: Flow
      waveforms were obtained in 48 patients proximal and distal to superficial femoral
      artery (SFA) disease using the 2D cine PC technique with velocity encoding (venc)
      = 100 cm/second. Flow data were correlated with SFA disease severity and compared
      with data from nine healthy volunteers. RESULTS: Of 96 arterial segments in 48
      patients, 26 were patent or only mildly stenotic, 35 had moderate-to-severe
      stenosis, and 35 were occluded. The flow patterns tended to become low-resistant
      below severe stenoses or occlusion. The mean peak flow velocity above/below SFA
      lesions was significantly higher in patients with severe disease (1.9 +/- 1.0, P
      = 0.01) or occlusion (2.0 +/- 1.0, P = 0.003) compared to normal volunteers (1.4
      +/- 0.6). The delay in peak velocity below the lesions showed a significant
      positive correlation with lesion severity (r = 0.65, P < 0.001). The mean flow
      volume ratio above/below SFA lesions was greater in patients with occluded
      vessels compared to normal volunteers (3.9 and 2.3 respectively; P = 0.04).
      CONCLUSION: Cine PC flow waveform changes across atherosclerotic lesions
      correlate with disease severity. This may help determine which lesions are
      hemodynamically significant.

PMID- 16463305
TI  - Proton MR spectroscopy in hyperhomocysteinemia with elevated blood methionine
      levels.
AB  - Proton magnetic resonance spectroscopy imaging (MRSI) and serial MRI were
      performed on a 10-year-old girl with B6 unresponsive cystathionine B-synthase
      (CBS) deficiency who developed high methionine levels while on betaine therapy.
      At presentation, T2-weighted sequences showed diffuse white matter (WM)
      hyperintensity and sulcal effacement, while MRSI metabolite concentrations were
      normal. Four months later, after the betaine therapy was discontinued and a
      methionine-restricted diet with vitamin B6, B12, and folate supplementation was
      initiated, blood methionine levels and MRI findings returned to normal. Normal
      MRSI at presentation was predictive of a positive outcome despite the markedly
      abnormal initial MRI results.

PMID- 16463306
TI  - Effects of gadopentetate dimeglumine and gadodiamide on serum calcium, magnesium,
      and creatinine measurements.
AB  - PURPOSE: To investigate the in vivo effects of gadodiamide (Gd-DTPA-BMA) and
      gadopentetate dimeglumine (Gd-DTPA) on the laboratory measurements of serum
      calcium, magnesium, and creatinine. MATERIALS AND METHODS: Medical records from
      1993 to 2004 were reviewed to identify inpatients for whom laboratory data were
      available regarding serum calcium, creatinine, and magnesium levels before and
      within one day after gadodiamide and gadopentetate dimeglumine enhanced MRI.
      Patients who underwent both gadolinium (Gd)-enhanced MRI and iodinated contrast
      enhanced examinations on separate days within a six-month period were also
      identified to compare changes in serum creatinine. RESULTS: Serum creatinine did
      not increase in 2788 cases following gadopentetate dimeglumine and gadodiamide
      injection. By comparison, serum creatinine increased from 1.21 to 1.28 mg/dL
      following iodinated contrast, and there were 20 cases (2.6%) of contrast-induced
      nephrotoxicity (P < 0.01). Gadopentetate dimeglumine did not affect serum calcium
      or magnesium measurements. Following 1157 gadodiamide-enhanced examinations,
      measured serum calcium spuriously dropped from 8.65 to 8.33 mg/dL (P < 0.0001)
      and 34 patients had spurious critical hypocalcemia (<6 mg/dL). Of 60 patients
      with high-dose gadodiamide injection and renal insufficiency, 36.7% (N = 22) had
      spurious critical hypocalcemia immediately post MRI. In 216 patients with renal
      insufficiency, the mean serum magnesium level increased slightly from 1.69 to
      1.77 mEq/L following gadodiamide injection (P < 0.0001). CONCLUSION: Gd-based
      contrast agents are safe for MRI and MR angiography (MRA), and do not induce
      nephrotoxicity. However, gadodiamide interferes with serum calcium and magnesium
      measurements-particularly at high doses and/or with renal insufficiency.

PMID- 16463307
TI  - Direct quantitative in vivo comparison of calcified atherosclerotic plaque on
      vascular MRI and CT by multimodality image registration.
AB  - PURPOSE: To investigate direct volumetric in vivo correspondence of calcified
      atherosclerotic plaque lesions in MRI and CT images of the thoracic aorta by
      multimodality image registration and fusion. MATERIALS AND METHODS: Twelve CT (11
      noncontrast and one contrast) and MRI (TruFISP, contrast T1-weighted volumetric
      interpolated breath-hold examination (VIBE)) data sets were co-registered by
      approximate segmentation of the aorta and subsequent automatic co-registration by
      maximization of mutual information (MI). We quantitatively assessed 22 co
      registered calcified plaque lesions on CT and MRI. RESULTS: The three-dimensional
      registration consistency and accuracy were 1.74 +/- 1.3 mm, and 2.42 +/- 1.65 mm,
      respectively. The ratio of CT/MRI calcified plaque volume decreased
      asymptotically with MRI volume, and correlated with average CT lesion density (r
      = 0.72) for small lesions (<25 mm(3)). The average calcified plaque volume,
      circumferential extent, and maximal radial width by MRI were significantly
      smaller compared to CT (35%, 68%, and 53%, respectively; P < 0.05). CONCLUSION:
      Software co-registration allowed precise, direct, and voxel-based comparison of
      calcified atherosclerotic plaque lesions imaged by MRI and CT. In comparison with
      co-registered MRI, overestimation of calcified plaque in aortic CT due to
      "blooming" correlates with the average lesion density for small plaques, and is
      greater for small plaques.

PMID- 16463308
TI  - Nested frailty models using maximum penalized likelihood estimation.
AB  - The frailty model is a random effect survival model, which allows for unobserved
      heterogeneity or for statistical dependence between observed survival data. The
      nested frailty model accounts for the hierarchical clustering of the data by
      including two nested random effects. Nested frailty models are particularly
      appropriate when data are clustered at several hierarchical levels naturally or
      by design. In such cases it is important to estimate the parameters of interest
      as accurately as possible by taking into account the hierarchical structure of
      the data. We present a maximum penalized likelihood estimation (MPnLE) to
      estimate non-parametrically a continuous hazard function in a nested gamma
      frailty model with right-censored and left-truncated data. The estimators for the
      regression coefficients and the variance components of the random effects are
      obtained simultaneously. The simulation study demonstrates that this semi
      parametric approach yields satisfactory results in this complex setting. In order
      to illustrate the MPnLE method and the nested frailty model, we present two
      applications. One is for modelling the effect of particulate air pollution on
      mortality in different areas with two levels of geographical regrouping. The
      other application is based on recurrent infection times of patients from
      different hospitals. We illustrate that using a shared frailty model instead of a
      nested frailty model with two levels of regrouping leads to inaccurate estimates,
      with an overestimation of the variance of the random effects. We show that even
      when the frailty effects are fairly small in magnitude, they are important since
      they alter the results in a systematic pattern.

PMID- 16463309
TI  - A maximum likelihood method for studying gene-environment interactions under
      conditional independence of genotype and exposure.
AB  - Given the biomedical interest in gene-environment interactions along with the
      difficulties inherent in gathering genetic data from controls, epidemiologists
      need methodologies that can increase precision of estimating interactions while
      minimizing the genotyping of controls. To achieve this purpose, many
      epidemiologists suggested that one can use case-only design. In this paper, we
      present a maximum likelihood method for making inference about gene-environment
      interactions using case-only data. The probability of disease development is
      described by a logistic risk model. Thus the interactions are model parameters
      measuring the departure of joint effects of exposure and genotype from
      multiplicative odds ratios. We extend the typical inference method derived under
      the assumption of independence between genotype and exposure to that under a more
      general assumption of conditional independence. Our maximum likelihood method can
      be applied to analyse both categorical and continuous environmental factors, and
      generalized to make inference about gene-gene-environment interactions. Moreover,
      the application of this method can be reduced to simply fitting a multinomial
      logistic model when we have case-only data. As a consequence, the maximum
      likelihood estimates of interactions and likelihood ratio tests for hypotheses
      concerning interactions can be easily computed. The methodology is illustrated
      through an example based on a study about the joint effects of XRCC1
      polymorphisms and smoking on bladder cancer. We also give two simulation studies
      to show that the proposed method is reliable in finite sample situation.

PMID- 16463311
TI  - Solid-state NMR spectroscopy: molecular structure and organization at the atomic
      level.

PMID- 16463312
TI  - Molecular recognition of a three-way DNA junction by a metallosupramolecular
      helicate.

PMID- 16463313
TI  - The effects of salinity and other factors on nitrite reduction by Ochrobactrum
      anthropi 49187.
AB  - The nitrite reductase (NIR) gene was cloned from Ochrobactrum anthropi 49187 and
      found to contain an open reading frame of 1131 nucleotides, encoding a
      polypeptide of 376 amino acids. The O. anthropi NIR gene encodes a copper-type
      dissimilatory reductase based on sequence homology with other genes. The
      polypeptide product is predicted to form a trimeric holoenzyme of 37 kDa subunits
      based on molecular weight estimates of extracts in activity gels. Expression of
      the enzyme is up-regulated by nitrate, presumably through the intermediate
      nitrite, and its activity is influenced by inhibitors. Salinity enhances the
      activity of existing NIR enzyme, but appears to decrease the expression of new
      enzyme.

PMID- 16463314
TI  - A simple system for biofilm potential monitoring in drinking water.
AB  - SAGEP-EAU DE PARIS produces drinking water for the city of Paris (France). In
      order to supply a high quality water, one of the main SAGEP's concerns is to
      monitor the Biofilm Formation Potentials of the produced drinking waters. Biofilm
      incubators were installed at the outlet of three Water Treatment Plants (WTP).
      These incubators allowed biofilm formation and quantification in terms of Fixed
      Total Organic Carbon (FTOC), fixed culturable bacteria (HPC-R2A) and fixed total
      bacteria. During this study, quantitative differences appeared between the
      biofilms formed at the outlet of the three WTPs, leading to different
      classifications of the Biofilm Formation Potentials of the three produced waters,
      depending on the used parameter for biofilms quantification. This observation
      underlined the necessity of a multi-parametric approach for the study of
      biofilms. More generally, our results validated the use of these sturdy stainless
      steel incubators, highly adapted to industrial field conditions, for the
      monitoring of Biofilm Formation Potentials in drinking water networks.

PMID- 16463315
TI  - Decolorization of synthetic dyes by the deuteromycete Pestalotiopsis guepinii
      CLPS no. 786 strain.
AB  - The ability of Pestalotiopsis guepinii CLPS no. 786 to decolorize 13 dyes of
      varied structure was analyzed and compared with that of the basidiomycete
      Phanerochaete chrysosporium . Nine dyes representing anthrapyridone, azo, N
      heterocyclic and triphenylmethane chromophores, but none with the O-heterocyclic
      group, were decolorized by P. guepinii when added to an agar medium. Studies with
      liquid cultures revealed that P. guepinii transformed both crystal violet and
      methylene blue B dyes, and adsorbed different chromophores onto its mycelium.

PMID- 16463316
TI  - Adsorptive removal of textile dyes from aqueous solutions by dead fungal biomass.
AB  - Dead fungal biomass prepared from Phanerochaete chrysosporium and Funalia trogii
      was tested for their efficiency in removal of textile dyes. The effects of
      contact time, initial dye concentration, amount of dead biomass and agitation
      rate on dye removal have been determined. Removal of all dyes required a very
      short time (60 min). Experimental results show that, P. chrysosporium was more
      effective than F. trogii . An increase in the amount of dead biomass positively
      affected of the dye removal. The removal efficiency of different amount of
      biomass was in order 1 g > 0.5 g > 0.2 g > 0.1 g. The highest removal was
      obtained at 150-200 rpm. Slightly lower removing activities were found at lower
      agitation rates. This study showed that it was possible to remove textile dyes by
      dead biomass of P. chrysosporium .

PMID- 16463317
TI  - Phenotypic characterization of food waste degrading Bacillus strains isolated
      from aerobic bioreactors.
AB  - A phenotypic characterization of seventeen Bacillus strains isolated from aerobic
      thermophilic bioreactors of a food waste processing company was carried out,
      using fatty acid and enzymatic activity profiles. It was observed that each
      species possessed a typical fatty acid and enzymatic production profile. Bacillus
      licheniformis strains exhibited the most significant enzyme production. Numerical
      analyses (principal component and hierarchical cluster analyses) revealed that
      Bacillus licheniformis strains were homogeneous regarding their fatty acid
      profiles whilst B. subtilis and Bacillus pumilus strains showed some phenotypic
      differences. However, enzymatic activities numerical analyses indicated that
      these three Bacillus species were more homogeneous regarding this phenotypic
      characteristic.

PMID- 16463318
TI  - The thioredoxin system from Streptomyces coelicolor.
AB  - This paper describes the cloning, purification and characterization of
      thioredoxin (TrxA) and thioredoxin reductase (TrxR) from bacterial strain
      Streptomyces coelicolor . The genes of S. coelicolor encoding TrxA and TrxR were
      amplified by polymerase chain reaction, inserted into pET expression vector and
      used to overexpress these proteins in Escherichia coli . TrxA and TrxR were
      produced as the hexahistidine fusion proteins and were recovered from the
      cytoplasm as the soluble proteins. The activity of the purified recombinant
      proteins was demonstrated. The activity of TrxA was shown by efficient reduction
      of insulin and activity of NADPH-dependent TrxR was revealed by catalyses of 5,5'
      dithiobis (2-nitrobenzoic acid) (DTNB) reduction reaction. The reduction reaction
      was fully dependent upon the presence of TrxA as intermediate electron carrier
      with the pH optimum 7.5 and the temperature optimum 29 degrees C. Km value of
      TrxR for TrxA was 0.217 +/- 0.02 microM.

PMID- 16463319
TI  - Identification of nif genes in N2-fixing bacterial strains isolated from rice
      fields along the Yangtze River Plain.
AB  - The aim of this research was to identify nifH and nifHDKYE ' genes in twenty
      strains of N2-fixing heterotrophic bacteria isolated from rice fields in the
      Yangtze River Plain. Southern hybridization of the total DNA from each strain was
      performed with the Klebsiella pneumoniae nifHDKYE ' gene probe (6.2 kb Eco RI
      fragment from pSA30) and the Azospirillum brasilense nifH gene probe (0.6 kb Eco
      RI-Hin dIII fragment from pHU8). We found that Eco RI fragments of total DNA from
      Aeromonas hydrophila HY2, Bacillus azotoformans FD, Bacillus licheniformis NCH1,
      NCH5, WH4, Bacillus brevis NC2, Bacillus pumilus NC12, Bacillus cereus NCH2,
      Citrobacter freundii HY5, HY9, Derxia gummosa HZ5, Pseudomonas mendocina HZ1 and
      Pseudomonas pseudoalcaligenes WH3 were positively hybridized with both of the
      probes. Agrobacterium radiobacter HY17, Corynebacterium sp. HY12, YZ and
      Pseudomonas sp. HY11 had Eco RI fragments hybridized with the K. pneumoniae
      nifHDKYE ' gene probe. An Eco RI fragment of total DNA from Bacillus megaterium
      YY4 was positively hybridized to the A. brasilense nifH gene probe. No
      hybridization sign was found in the total DNA fragments from Alcaligenes cupidus
      YY6 and Corynebacterium sp. NC11 hybridized with either of the gene probes. The
      data provide the number and size of EcoRI fragments of the total DNA hybridized
      with the nif gene probes for these strains of rarely studied species, suggesting
      additional evidence for N2 fixing and nif gene diversity of N2-fixing bacteria in
      rice fields along the Yangtze River Plain.

PMID- 16463320
TI  - Unusual envelopes associated with parasporal inclusions of a mosquitocidal
      Bacillus thuringiensis serovar fukuokaensis isolate.
AB  - A mosquitocidal soil isolate of Bacillus thuringiensis serovar fukuokaensis
      (H3ade) produced spherical parasporal inclusions measuring 0.6-0.7 microm in
      diameter. Inclusion matrix was homogeneous substance surrounded by a thick,
      highly electron-dense envelope 30-50 nm in thickness. The envelopes were
      associated with both intracellular and extracellular inclusions. Densely woven
      network was the inner structure of the envelope. Often, inclusions had round
      shaped, enveloped small protrusions on the surface.

PMID- 16463322
TI  - Hermann Staudinger Award 2006.
AB  - Macromolecular News: This section contains news of the macromolecular community
      all over the world. Articles about, for example, people, projects, and market
      trends are welcome. Suggestions should be sent to the editorial office of the
      Macromolecular journals, preferably by E-mail to macromol@wiley-vch.de. The
      editorial office decides which articles will be published.

PMID- 16463321
TI  - Biodegradation of gallotannins and ellagitannins.
AB  - Nowadays, many researches have been made on gallotannin biodegradation and have
      gained great success in further utilization. Some of industrial applications of
      these findings are in the production of tannase, the biotransformation of tannic
      acid to gallic acid or pyrogallol and detannification of food and fodder.
      Although ellagitannins have the typical C-C bound which is more difficult to be
      degraded than gallotannins, concerted efforts are still in progress to improve
      ellagitannin degradation and utilization. Currently, more attention is mainly
      focused on intestinal microflora biodegradation of tannins especially
      ellagitannins which can contribute to the definition of their bioavailability for
      both human beings and ruminants. Also there have been endeavours to utilize the
      tannin-degrading activity of different fungi for ellagitannin-rich biomass, which
      will facilitate application of tannin-degrading enzymes in strategies for
      improving industrial and livestock production. Due to the complicated structures
      of complex tannins and condensed tannins, the biodegradation of them is much more
      difficult and there are fewer researches on them. Therefore, the researches on
      the mechanisms of gallotannin and ellagitannin biodegradation can result in the
      overall understanding to the biodegradation of complex tannins and condensed
      tannins. Biodegradation of tannins is in an incipient stage and further studies
      have to be carried out to exploit the potential of various tannins for largescale
      applications in food, fodder, medicine and tannery effluent treatment.

PMID- 16463324
TI  - Microwave synthesis of nanoporous materials.
AB  - Studies in the last decade suggest that microwave energy may have a unique
      ability to influence chemical processes. These include chemical and materials
      syntheses as well as separations. Specifically, recent studies have documented a
      significantly reduced time for fabricating zeolites, mixed oxide and mesoporous
      molecular sieves by employing microwave energy. In many cases, microwave
      syntheses have proven to synthesize new nanoporous structures. By reducing the
      times by over an order of magnitude, continuous production would be possible to
      replace batch synthesis. This lowering of the cost would make more nanoporous
      materials readily available for many chemical, environmental, and biological
      applications. Further, microwave syntheses have often proven to create more
      uniform (defect-free) products than from conventional hydrothermal synthesis.
      However, the mechanism and engineering for the enhanced rates of syntheses are
      unknown. We review the many studies that have demonstrated the enhanced syntheses
      of nanoporous oxides and analyze the proposals to explain differences in
      microwave reactions. Finally, the microwave reactor engineering is discussed, as
      it explains the discrepancies between many microwave studies.

PMID- 16463325
TI  - Resonant X-ray scattering: a tool for structure elucidation in liquid crystals.
AB  - The use of resonant X-ray scattering to determine structures in liquid crystal
      systems is surveyed. This powerful experimental technique utilises "forbidden
      reflections" to determine the subtle differences in interlayer orientation that
      differentiate several smectic systems. The technique relies on the materials
      containing an atom to which the X-ray energy can be tuned, usually sulphur or
      selenium. Experiments are often carried out on free-standing films that provide a
      highly monodomain structure that allows high-resolution measurements to be made,
      and, hence, structural details to be determined. Alternatively, resonant
      scattering has been demonstrated for materials contained in glass devices that
      permit the application of electric fields to the system, in a manner analogous to
      that used in liquid crystal devices. The resonant scattering technique provides
      unequivocal descriptions of the packing in smectic systems, and the way in which
      the packing is distorted in electric fields. This Minireview describes the
      principles behind resonant X-ray scattering, its application to liquid crystals
      and some of the potential for the future.

PMID- 16463326
TI  - Electrochemical synthesis and fabrication of gold nanostructures based on poly(N
      vinylpyrrolidone).

PMID- 16463327
TI  - Assessing arterial blood flow and vessel area variations using real-time zonal
      phase-contrast MRI.
AB  - PURPOSE: To measure peripheral artery function using a real-time phase-contrast
      (PC)-MRI sequence with tailored image-processing algorithms for flow computation.
      MATERIALS AND METHODS: An approach to real-time flow measurements was developed
      based on two-dimensional spatially selective excitation pulses and consecutive
      tailored processing of the data to derive blood flow and vessel area variations.
      The data acquisition strategy allows for flow measurements at high spatial and
      temporal resolutions of 1 mm(2) and 50 msec, respectively. In postprocessing the
      vessel area is automatically extracted using correlation measures in conjunction
      with morphological image operators. By means of in vitro and in vivo validations,
      it is shown that the current methods provide accurate and reproducible
      measurements of flow and vessel area variations. RESULTS: In vitro the comparison
      between the lumen area measured with the presented method and the values obtained
      by caliper gauge measurement showed a difference of 3.4% +/- 3.4% (mean +/- 2
      SD). Similarly, the comparison between the stroke volumes determined with the
      presented method and by stopwatch and bucket measurements yielded a difference of
      6.1% +/- 2.1%. In vivo the results from the real-time measurements for lumen area
      and stroke volume were compared with those from a gated PC-MRI technique with
      differences of 4.8% +/- 14% and 3.0% +/- 24.7%, respectively. CONCLUSION: The
      presented method constitutes a reliable tool set for quantifying the variations
      of blood flow and lumen area in the superficial femoral artery during reactive
      hyperemia and for studying their correlation with cardiovascular risk factors.

PMID- 16463328
TI  - A C2 molecule entrapped in the pentagonal-dodecahedral Y2 cage in Y2C2@C82(III).

PMID- 16463329
TI  - Femtosecond relaxation dynamics of solvated electrons in liquid ammonia.
AB  - The ultrafast relaxation dynamics of the well-known solvated electron in liquid
      ammonia solutions are investigated with femtosecond near-infrared pump-probe
      absorption spectroscopy. Immediately after photoexcitation, the dynamic
      absorption spectrum of the electron is substantially red-shifted with respect to
      its stationary spectrum. A subsequent dynamic blue shift of the pump-probe
      spectrum occurs on a timescale of 150 fs. The data are understood in terms of
      ground-state "cooling" and can be quantitatively simulated by an intuitive
      temperature-jump model employing a dynamically evolving Kubo line shape for the
      electronic resonance. A simple estimate implies that, on average, the electron in
      the liquid is coordinated to six nearest-neighbor ammonia molecules. An
      equivalent analysis of the data based on a bubble-formation/cavity-contraction
      mechanism is briefly outlined.

PMID- 16463330
TI  - Theoretical study on the structures and electronic spectra of TCNE2-.
AB  - Investigations into the charge-separated states and electron-transfer transitions
      in tetracyanoethylene (TCNE) complexes have recently generated much interest. In
      this work we present theoretical calculations showing that the most stable
      structure of the dianion TCNE2- has D2d symmetry in vacuum as well as in the
      solvents dichloromethane and acetonitrile. By means of the coupled cluster linear
      response, we compute the vertical electronic spectrum in both the gas phase and
      solution. The theoretical results are compared to the experimental data and good
      agreement is achieved.

PMID- 16463332
TI  - Optical properties of gas-phase tryptophan-silver cations: charge transfer from
      the indole ring to the silver atom.
AB  - We present a joint experimental and theoretical investigation of the electronic
      excitation spectra of the tryptophan-silver complex. The photodissociation
      spectrum of gas-phase [Trp-Ag]+ was measured from 215 to 330 nm using a
      quadrupole ion trap coupled to an optical parametric-oscillator laser. The
      calculated time-dependent density functional theory (TD-DFT) absorption spectra
      for different prototypes of structures are presented. Low-energy transitions that
      are experimentally observed are only calculated for the charge-solvation (CS)
      structures. These transitions are a signature of the metal-pi interaction in [Trp
      Ag]+. The recorded spectrum is compared to a Boltzmann average of the absorption
      spectrum obtained from direct molecular dynamics (MD) simulations involving
      simultaneous transitions to excited states based on semiempirical configuration
      interaction (CI) calculations. The results demonstrate that charge transfer can
      be photoinduced from the indole ring to the silver atom.

PMID- 16463331
TI  - Enantiodiscrimination between an N-acetyl-L-cysteine SAM and proline: an in situ
      spectroscopic and computational study.
AB  - A combination of attenuated total reflection infrared (ATR-IR) and modulation
      excitation spectroscopy (MES) is used to study the enantiodiscriminating
      interactions between proline and a chiral, self-assembled monolayer (SAM) of N
      acetyl-L-cysteine on gold. The N-acetyl-L-cysteine SAM consists of a mixture of
      protonated and deprotonated molecules. Whereas both species are influenced by
      adsorbed proline, only the deprotonated molecules are involved in
      enantiodiscrimination. Density functional theory (DFT) calculations reveal that
      electrostatics dominates the interaction between the two molecules. By modulating
      the absolute configuration of proline over the chiral SAM, and a subsequent phase
      sensitive detection of the periodically varying signals in the ATR-IR spectra,
      the small spectral differences between the diastereomeric complexes are spotted.
      The resulting difference spectrum is in qualitative agreement with the spectrum
      predicted by the DFT calculations.

PMID- 16463333
TI  - Homolysis of N-alkoxyamines: a computational study.
AB  - During nitroxide-mediated polymerization (NMP) in the presence of a nitroxide
      R2(R1)NO*, the reversible formation of N-alkoxyamines [P-ON(R1)R2] reduces
      significantly the concentration of polymer radicals (P*) and their involvement in
      termination reactions. The control of the livingness and polydispersity of the
      resulting polymer depends strongly on the magnitude of the bond dissociation
      energy (BDE) of the C-ON(R1)R2 bond. In this study, theoretical BDEs of a large
      series of model N-alkoxyamines are calculated with the PM3 method. In order to
      provide a predictive tool, correlations between the calculated BDEs and the
      cleavage temperature (Tc), and the dissociation rate constant (k(d)), of the N
      alkoxyamines are established. The homolytic cleavage of the N-OC bond is also
      investigated at the B3P86/6-311++G(d,p)//B3LYP/6-31G(d), level. Furthermore, a
      natural bond orbital analysis is carried out for some N-alkoxyamines with a O-C
      ON(R1)R2 fragment, and the strengthening of their C-ON(R1)R2 bond is interpreted
      in terms of stabilizing anomeric interactions.

PMID- 16463335
TI  - A theoretical study of the structure and bonding of UOX4 (X = F, Cl, Br, I)
      molecules: the importance of inverse trans influence.
AB  - During nitroxide-mediated polymerization (NMP) in the presence of a nitroxide
      R2(R1)NO*, the reversible formation of N-alkoxyamines [P-ON(R1)R2] reduces
      significantly the concentration of polymer radicals (P*) and their involvement in
      termination reactions. The control of the livingness and polydispersity of the
      resulting polymer depends strongly on the magnitude of the bond dissociation
      energy (BDE) of the C-ON(R1)R2 bond. In this study, theoretical BDEs of a large
      series of model N-alkoxyamines are calculated with the PM3 method. In order to
      provide a predictive tool, correlations between the calculated BDEs and the
      cleavage temperature (T(c)), and the dissociation rate constant (k(d)), of the N
      alkoxyamines are established. The homolytic cleavage of the N-OC bond is also
      investigated at the B3P86/6-311++G(d,p)//B3LYP/6-31G(d), level. Furthermore, a
      natural bond orbital analysis is carried out for some N-alkoxyamines with a O-C
      ON(R1)R2 fragment, and the strengthening of their C-ON(R1)R2 bond is interpreted
      in terms of stabilizing anomeric interactions.

PMID- 16463334
TI  - Potential energy surfaces of the microhydrated guanine...cytosine base pair and
      its methylated analogue.
AB  - A complete scan of the potential and free-energy surfaces of monohydrated and
      dihydrated guanine...cytosine and 9-methylguanine...1-methylcytosine base pairs
      was realized by the molecular dynamics/quenching technique using the force field
      of Cornell et al. implemented in the AMBER7 program. The most stable and
      populated structures localized were further fully reoptimized at the correlated
      ab initio level employing the resolution of identity Moller-Plesset method with a
      large basis set. A systematic study of microhydration of these systems using a
      high-level correlated ab initio approach is presented for the first time. The
      different behavior of guanine...cytosine and adenine...thymine complexes is also
      discussed. These studies of nucleic acid base pairs are important for finding
      binding sites of water molecules around bases and for better understanding of the
      influence of the solvent on the stability of the structure of DNA.

PMID- 16463336
TI  - Computational studies on the cyclization of polycyclic aromatic hydrocarbons in
      the synthesis of curved aromatic derivatives.
AB  - Computational studies on the cyclization reactions of some polycyclic aromatic
      hydrocarbons (PAHs) were performed at the DFT level. Compounds C26H14 and C24H14,
      which show the connectivity of C60 fullerene fragments, were chosen as suitable
      models to study the formation of curved derivatives by six- or five-membered ring
      formation, upon oxidation to their radical cations. Four possible pathways for
      the cyclization process were considered: a) initial C-C bond formation to afford
      a curved derivative, followed by dehydrogenation; b) homolytic C-H cleavage prior
      to cyclization; c) initial concerted H2 elimination and subsequent cyclization;
      and d) deprotonation of the radical cations prior to cyclization. Computed
      reaction and activation energies for these reactions show that direct cyclization
      from radical cations (pathway a) is the lowest-energy mechanism. The formation of
      five-membered rings is somewhat more favourable than benzannulation. After new
      cycle formation, homolytic C-H dissociation to afford the corresponding cations
      is the most favourable process. These cations react with H* without barrier to
      give H2* Intermediate deprotonations are strongly disfavoured. The relatively low
      activation energies compared with carbon cage rearrangements suggest that
      ionization of PAHs can be used for the tailored preparation of nonplanar
      derivatives from suitable precursors.

PMID- 16463337
TI  - In situ and online monitoring of hydrodynamic flow profiles in microfluidic
      channels based upon microelectrochemistry: optimization of electrode locations.
AB  - Herein, we extend our previous approach concerning the reconstruction of profiles
      of pressure-driven hydrodynamic flow in microfluidic channels based on current
      measurements at band electrode(s) [see the preceding paper ChemPhysChem 2005, 6,
      1581]. We address the central issue of optimization of geometrical parameters
      describing the electrode(s) assembly (a single band and two bands working in
      generator-collector mode) within the channel flow cell to enhance the speed and
      precision of the flow profile reconstruction method.

PMID- 16463338
TI  - A kinetic study of the reaction between N,N-dimethyl-p-toluidine and its
      electrogenerated radical cation in a room temperature ionic liquid.
AB  - The reaction between N,N-dimethyl-p-toluidine (DMT) and the radical cation
      generated through its one-electron oxidation has been studied electrochemically
      in the room temperature ionic liquid N-methyl-N-butylpyrrolidinium
      bis(trifluoromethylsulfonyl)imide, [Py14][NTf2]. Kinetic information obtained as
      linear sweep and cyclic voltammetry collected at 5 microm, 10 microm and 0.3 mm
      diameter platinum disk electrodes over a range of initial substrate
      concentrations and scan rates spanning five orders of magnitude was complemented
      by chronoamperometric measurements designed to probe the rate of diffusion. At
      the fastest scan rates the homogeneous reactions following the initial electron
      transfer were effectively out-run, facilitating an assessment of the electrode
      kinetics using DIGISIM and a validated Nicholson's method. Through digital
      simulation the voltammetry was then shown to be consistent with a mechanism
      established for the same reaction in acetonitrile, involving dimerisation of the
      DMT radicals following an initial and rate-determining proton transfer step.
      After careful consideration of all parameters, a bimolecular rate constant of
      (3.4 +/- 1.1) x 10(2) dm3 mol(-1) s(-1) was deduced by fitting the data. This was
      compared to the equivalent value for acetonitrile and, in light of this, the
      implications on the viability of ionic liquids for use as alternative mainstream
      solvents briefly assessed.

PMID- 16463340
TI  - Swallowing, arterial pulsation, and breathing induce motion artifacts in carotid
      artery MRI.
AB  - PURPOSE: To identify and quantify the potential sources of motion in carotid
      artery imaging. MATERIALS AND METHODS: Two healthy volunteers and 12 patients (20
      75 years old) with atherosclerotic disease were scanned on a Philips Intera 1.5T
      system. A single-shot balanced-fast field echo (bFFE) sequence was used to
      acquire real-time axial views of the carotid artery wall (three images per
      second). A three-step acquisition protocol was performed to analyze the three
      types of motion (arterial pulsation, breathing, and swallowing) separately. The
      isocenter carotid artery motion amplitude in either the x or y direction was
      measured. Radial variation in the carotid lumen between the systolic and
      diastolic phases was analyzed. Motion frequency was reported for each patient.
      RESULTS: Significant motion related to arterial pulsation (amplitude = 0.27-0.93
      mm, mean = 0.6, SD = 0.19), breathing (amplitude = 0.5-3.6 mm, mean = 1.56, SD =
      0.99)), and swallowing (amplitude = 1.4-9.2 mm, mean = 4.7, SD = 2.4) were
      visualized. CONCLUSION: Pulsation, breathing, and swallowing are sources of
      significant motion in the carotid artery wall. Such motion should be considered
      in the future to improve carotid artery image quality.

PMID- 16463341
TI  - Acoustic noise characteristics of a 4 Telsa MRI scanner.
AB  - PURPOSE: To quantify the acoustic noise characteristics of a 4 Tesla MRI scanner,
      and determine the effects of structural acoustics and gradient pulse excitations
      on the sound field so that feasible noise control measures can be developed.
      MATERIALS AND METHODS: Acoustic noise emissions were measured in the ear and
      mouth locations of a typical adult. The sound pressure measurements were acquired
      simultaneously with the electrical current signals of the gradient pulses. Two
      forms of gradient waveforms (impulsive and operating pulses) were studied.
      RESULTS: The sound pressure levels (SPLs) emitted by the MRI scanner operating in
      echo-planar imaging (EPI) mode were in the range of 120-130 decibels. Three types
      of sound pressure responses were observed in the EPI sequences: 1) harmonic, 2)
      nonharmonic, and 3) broadband. The frequency-encoding gradient pulses were the
      most dominant and produced generally odd-number harmonics and nonharmonics. The
      phase-encoding gradient pulses generated mostly even-number harmonics, and the
      slice-selection gradient pulses produced primarily a broadband spectrum.
      CONCLUSION: The operating condition acoustic spectrum can be predicted from the
      magnet-structural acoustic transfer functions, which are independent of imaging
      sequences. This finding is encouraging because it shows that it is possible to
      treat such noises with an active noise control application.

PMID- 16463342
TI  - Long-term effects of bilateral subthalamic nucleus stimulation on health-related
      quality of life in advanced Parkinson's disease.
AB  - We evaluated the long-term effects of subthalamic nucleus (STN) stimulation on
      health-related quality of life (HRQL) in patients with advanced Parkinson's
      disease (PD). STN stimulation improves motor function and decreases medication
      requirements in patients with advanced PD. The impact of STN stimulation on HRQL
      is less well established, especially beyond 1 year after surgery. We report HRQL
      outcomes for 18 patients with advanced PD. Patients were evaluated with the
      Parkinson's Disease Questionnaire-39 (PDQ-39), the Medical Outcome Study Short
      Form (SF-36), and the EuroQol visual analogue scale (VAS) before surgery, 6
      months postoperatively, and at a long-term follow-up visit (mean, 35.9 months;
      range, 18-57 months after surgery). Preoperative scores on HRQL measures were
      compared to results obtained at short- and long-term follow-up evaluations. The
      VAS and all domains of the PDQ-39 except for cognition, communication, and social
      support showed marked improvements at 6 months after surgery. At the long-term
      follow-up, there were sustained improvements in the VAS (63% improvement; P =
      0.0009) and in several domains of the PDQ-39 [mobility: 20%, P = 0.01; activities
      of daily living (ADL): 29%, P = 0.005; emotional well-being: 26%, P = 0.02;
      stigma: 43%, P = 0.003; and bodily discomfort: 35%, P = 0.007]. At the long-term
      evaluation, only the vitality domain of the SF-36 was significantly improved from
      baseline (16%; P = 0.01). In this selected group of patients, many of the short
      term gains in HRQL persist beyond 18 months after STN implantation. Benefits in
      nonmotor aspects of HRQL such as bodily discomfort and stigma appear to be among
      the most durable.

PMID- 16463343
TI  - Measurement of arterial input functions for dynamic susceptibility contrast
      magnetic resonance imaging using echoplanar images: comparison of physical
      simulations with in vivo results.
AB  - Measurement of the arterial input bolus shape is essential to the quantification
      of mean transit time and blood flow with dynamic susceptibility contrast (DSC)
      MRI. Input functions derived from the echoplanar signal intensity within or near
      arteries are highly nonlinear, yet such input functions are widely used. We
      employed a physical model for the echoplanar signal intensity from an artery as a
      function of contrast agent concentration, artery size, and angle to the magnetic
      field to test approaches for the measurement of the arterial input function. The
      simulated results confirmed the strong nonlinearity of signal in the neighborhood
      of vessels. Of the input function measurement methods considered, the simulations
      suggested that measurement of signal near but not within a large vessel is most
      accurate, but mean transit times (MTT) calculated with these input functions are
      highly sensitive to peak bolus concentration. Input functions determined from
      voxels demonstrating the shortest first moment overestimated the MTT but the
      measured MTTs were more robust to changes in peak concentration. Characteristics
      of the measured in vivo input functions were consistent with the simulations. Our
      results emphasize the important contribution of input function errors to the
      uncertainty in MTT and blood flow imaging with DSC MRI.

PMID- 16463344
TI  - In vivo proton electron double resonance imaging of the distribution and
      clearance of nitroxide radicals in mice.
AB  - Proton electron double resonance imaging (PEDRI) is an emerging technique that
      utilizes the Overhauser effect to enable in vivo and in vitro imaging of free
      radicals in biological systems. Nitroxide spin probes enable measurement of
      tissue redox state based on their reduction to diamagnetic hydroxylamines. PEDRI
      instrumentation at 0.02 T was applied to assess the ability to image the in vivo
      distribution, clearance, and metabolism of nitroxide radicals in living mice.
      Using phantoms of 2,2,5,5-tetramethyl-3-carboxylpyrrolidine-N-oxyl (PCA) in
      normal saline the dependence of the enhancement on RF power and spin probe
      concentration was determined. Enhancements of up to -23 were obtained in phantoms
      with 2 mM levels. Maximum enhancement of -7 was observed in vivo. Coronal images
      of nitroxide-infused mice enabled visualization of the kinetics of spin probe
      uptake and clearance in different organs including the great vessels, heart,
      lungs, kidneys, and bladder with an in-plane spatial resolution of 0.6 mm. PEDRI
      of living mice was also performed using 3-carbamoyl-proxyl and 2,2,6,6
      tetramethyl-4-oxopiperidine-N-oxyl to compare the different rate of clearance and
      metabolism among different nitroxide probes. PCA, due to its intravascular
      compartmentalization, provided the sharpest contrast for the vascular system and
      highest enhancement values in the PEDRI images among the three nitroxides.

PMID- 16463345
TI  - Robust analysis of short echo time (1)H MRSI of human brain.
AB  - Short echo time proton MR Spectroscopic Imaging (MRSI) suffers from low signal-to
      noise ratio (SNR), limiting accuracy to estimate metabolite intensities. A method
      to coherently sum spectra in a region of interest of the human brain by
      appropriate peak alignment was developed to yield a mean spectrum with increased
      SNR. Furthermore, principal component (PC) spectra were calculated to estimate
      the variance of the mean spectrum. The mean or alternatively the first PC (PC(1))
      spectrum from the same region can be used for quantitation of peak areas of
      metabolites in the human brain at increased SNR. Monte Carlo simulations showed
      that both mean and PC(1) spectra were more accurate in estimating regional
      metabolite concentrations than solutions that regress individual spectra against
      the tissue compositions of MRSI voxels. Back-to-back MRSI studies on 10 healthy
      volunteers showed that mean spectra markedly improved reliability of brain
      metabolite measurements, most notably for myo-inositol, as compared to regression
      methods.

PMID- 16463346
TI  - Use of G-CSF in matched sibling donor pediatric allogeneic transplantation: a
      consensus statement from the Children's Oncology Group (COG) Transplant
      Discipline Committee and Pediatric Blood and Marrow Transplant Consortium (PBMTC)
      Executive Committee.
AB  - Preliminary studies indicate that G-CSF-primed marrow harvesting may result in a
      graft with increased mononuclear cells collected, increased CD34(+) stem and
      progenitor cell dose and a potential for more rapid engraftment. Increased cell
      dose plus other potential positive effects of G-CSF priming have resulted in
      improved survival in non-randomized preliminary studies. These benefits may be
      available without the increased risk of chronic graft versus host disease (GVHD)
      that is experienced with allogeneic peripheral blood stem cell (PBSC) transplant.
      A phase III Children's Oncology Group (COG)/Pediatric Blood and Marrow Transplant
      Consortium (PBMTC) trial comparing G-CSF-primed marrow to standard marrow has
      been proposed. This document reviews background studies of G-CSF-primed marrow
      and addresses benefits and risks of G-CSF administration to normal pediatric
      donors. We conclude that the approach is promising and warrants further study.
      Risks of G-CSF to the donor are minimal and benefits to both donor and recipient
      may occur.

PMID- 16463347
TI  - Automatic algorithm for correcting motion artifacts in time-resolved two
      dimensional magnetic resonance angiography using convex projections.
AB  - Time-resolved contrast enhanced magnetic resonance angiography (MRA) may suffer
      from involuntary patient motion. It is noted that while MR signal change
      associated with motion is large in magnitude and has smooth phase variation in k
      phase, signal change associated with vascular enhancement is small in magnitude
      and has rapid phase variation in k-space. Based upon this observation, a novel
      projection onto convex sets (POCS) algorithm is developed as an automatic
      iterative method to remove motion artifacts. The presented POCS algorithm
      consists of high-pass phase filtering and convex projections in both k-space and
      image space. Without input of detailed motion knowledge, motion effects are
      filtered out, while vasculature information is preserved. The proposed method can
      be effective for a large class of nonrigid motions, including through-plane
      motion. The algorithm is stable and converges quickly, usually within five
      iterations. A double-blind evaluation on a set of clinical MRA cases shows that a
      completely unsupervised version of the algorithm produces significantly better
      rank scores (P=0.038) when compared to angiograms produced manually by an
      experienced radiologist.

PMID- 16463348
TI  - Hereditary spastic paraplegia associated with dopa-responsive parkinsonism.
AB  - A 47-year-old patient with hereditary spastic paraplegia and parkinsonian
      features is reported. Treatment with levodopa led to marked improvement in his
      neurological status and quality of life. However, several years later he
      developed motor fluctuations and dyskinesias. The latter promptly remitted with
      amantadine treatment.

PMID- 16463349
TI  - Inference for case-control studies when exposure status is both informatively
      missing and misclassified.
AB  - In case-control studies, it is common for a categorical exposure variable to be
      misclassified. It is also common for exposure status to be informatively missing
      for some individuals, in that the probability of missingness may be related to
      exposure. Procedures for addressing the bias due to misclassification via
      validation data have been extensively studied, and related methods have been
      proposed for dealing with informative missingness based on supplemental sampling
      of some of those with missing data. In this paper, we introduce study designs and
      analytic procedures for dealing with both problems simultaneously in a 2x2
      analysis. Results based on convergence in probability illustrate that the
      combined effects of missingness and misclassification, even when the latter is
      non-differential, can lead to naive exposure odds ratio estimates that are
      inflated or on the wrong side of the null. The motivating example comes from a
      case-control study of the association between low birth weight and the diagnosis
      of breast cancer later in life, where self-reported birth weight for some women
      is supplemented by accurate information from birth certificates.

PMID- 16463350
TI  - Cardiac and respiratory double self-gated cine MRI in the mouse at 7 T.
AB  - ECG-gated cardiac MRI in the mouse is hindered by many technical difficulties in
      ECG signal recording inside static and variable high magnetic scanner fields. The
      present study proposes an alternative robust method of acquiring auto-gated
      cardiac and respiratory cine images in mouse heart. In our approach, a motion
      synchronization signal is extracted from the echo peak MR signal of a non
      triggered radial acquisition. This signal is then used for both cardiac and
      respiratory retrospective gating before cine image reconstruction. Highly
      asymmetric echoes were acquired to achieve the radial k-space sampling in order
      to avoid radial acquisition related artifacts and to increase auto-gating
      robustness. In vivo experiments demonstrated the feasibility and robustness of
      self-gated cine-MRI in the mouse heart at 7T. The signal-to-noise and contrast-to
      noise ratios of the self-gated and ECG-gated images were comparable, all
      parameters being equal. Magn Reson Med, 2006. (c) 2006 Wiley-Liss, Inc.

PMID- 16463351
TI  - Contrast behavior and relaxation effects of conventional and hyperecho-turbo spin
      echo sequences at 1.5 and 3 T.
AB  - To overcome specific absorption rate (SAR) limitations of spin-echo-based MR
      imaging techniques, especially at (ultra) high fields, rapid acquisition
      relaxation enhancement/TSE (turbo spin echo)/fast spin echo sequences in
      combination with constant or variable low flip angles such as hyperechoes and
      TRAPS (hyperTSE) have been introduced. Due to the multiple spin echo and
      stimulated echo pathways involved in the signal formation, the contrast behavior
      of such sequences depends on both T2 and T1 relaxation times. In this work,
      constant and various variable flip angle sequences were analyzed in a volunteer
      study. It is demonstrated that a single effective echo time parameter TE(eff) can
      be calculated that accurately describes the overall T2 weighted image contrast.
      TE(eff) can be determined by means of the extended phase graph concept and is
      practically independent of field strength. Using the described formalism, the
      contrast of any TSE sequence can be predicted. HyperTSE sequences are
      demonstrated to show a robust and well-defined T2 contrast allowing clinical
      routine MRI to be performed with SAR reductions of typically at least 70%.

PMID- 16463352
TI  - Botulinum toxin changes intrafusal feedback in dystonia: a study with the tonic
      vibration reflex.
AB  - To investigate the possible role of botulinum toxin (BT-A) injection in reducing
      muscle afferent feedback, we evaluated electrophysiologically 10 right-handed
      patients with writer's cramp before and 3 weeks after treatment. The ratio
      between pre- and postinjection values of maximal M-wave (M-max), maximal
      voluntary contraction (MVC), and tonic vibration reflex (TVR) were measured in
      the injected muscles (wrist flexors or extensors). In all the subjects, BT-A
      injection reduced the TVR more than the M-max and MVC (mean ratio +/- SD: TVR,
      0.24 +/- 0.22; MVC, 0.59 +/- 0.32; M-max, 0.68 +/- 0.24; P = 0.003). Long-term
      evaluation of 2 patients disclosed that, after 7 months, when some clinical
      benefits persisted, M-max and MVC had fully recovered, whereas the TVR was still
      depressed. This special sensitivity of the TVR to suppression by BT-A injection
      could be mediated by the chemodenervation of intrafusal muscle fibers, leading to
      a reduction in spindle inflow to the central nervous system during vibration. The
      action on intrafusal fibers could alter sensorimotor integration, thus
      contributing to the clinical benefits of BT-A injection.

PMID- 16463353
TI  - MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage
      in multiple sclerosis.
AB  - Gray matter (GM) damage is an important pathophysiological feature in Multiple
      Sclerosis (MS), and may be related to clinical, including cognitive, deficits.
      Quantitative single-voxel (1)H-Magnetic Resonance Spectroscopy (TR/TE 6000/20 ms)
      was performed in 33 MS patients (11 per disease subtype; mean age 48 years, 16
      females) and 10 healthy controls (mean age 43 years, 7 females). No overall
      spectroscopic changes were found in MS cortex. In MS thalamus, a 9% decrease of N
      acetyl aspartate (NAA; P=0.005) and a 31% increase of myo-inositol (Ins; P=0.002)
      were found. A 21% Ins increase was observed (P=0.02) in MS hippocampus. Reduced
      NAA and increased Ins concentrations are thought to reflect neuro-axonal damage
      or loss and gliosis, respectively. Significant correlations between Ins
      concentrations and total-brain T(2) lesion load were found for MS thalamus
      (r=0.65, P<0.001) and hippocampus (r=0.57, P=0.001). MS thalamic and hippocampal
      Ins concentrations also correlated with each other (r=0.68; P<0.001). Cortical
      Gln correlated with thalamic NAA (r=-0.38; P=0.03) in MS. Thalamic and
      hippocampal Ins increases were most prominent in secondary-progressive (SP)
      patients (37% and 34%, respectively), whereas the largest thalamic NAA decrease
      (14%) was found in primary-progressive (PP) patients. In conclusion, thalamic and
      hippocampal GM pathology are important features of (progressive) MS.

PMID- 16463354
TI  - Fast low-angle dual spin-echo (FLADE): a new robust pulse sequence for structural
      imaging of trabecular bone.
AB  - Mechanical strength and fracture resistance of trabecular bone (TB) are largely
      determined by the structural arrangement of individual trabeculae. Fast 3D spin
      echo approaches are preferable to gradient echoes in that they are less sensitive
      to local induced gradients at the bone/marrow interface caused by magnetic
      susceptibility difference between the two tissues. FLASE is a 3D pulse sequence
      that serves this purpose. Here, we present a new pulse sequence dubbed FLADE
      (fast low-angle dual spin-echo) that overcomes some of the limitations inherent
      to FLASE, such as sensitivity to artifactual stimulated echoes. The double-echo
      sequence features a flip angle <90 degrees allowing for TR << T(1). The second
      phase-reversal pulse has the dual function of creating a second echo and
      restoring inverted longitudinal magnetization. The prolonged TR, made possible by
      sampling only half of k(z)-space, is used to collect navigator echoes in adjacent
      slabs for sensing subpixel translational displacements. FLADE is shown to provide
      SNR comparable to FLASE while having narrower point-spread function and being
      more robust to imperfections in the nonselective 180 degree pulses. Structural
      parameters derived from the in vivo images with the two pulse sequences are
      highly correlated, therefore suggesting that clinical data obtained with either
      pulse sequence can be merged.

PMID- 16463355
TI  - Confidence intervals for the amount of heterogeneity in meta-analysis.
AB  - Effect size estimates to be combined in a systematic review are often found to be
      more variable than one would expect based on sampling differences alone. This is
      usually interpreted as evidence that the effect sizes are heterogeneous. A random
      effects model is then often used to account for the heterogeneity in the effect
      sizes. A novel method for constructing confidence intervals for the amount of
      heterogeneity in the effect sizes is proposed that guarantees nominal coverage
      probabilities even in small samples when model assumptions are satisfied. A
      variety of existing approaches for constructing such confidence intervals are
      summarized and the various methods are applied to an example to illustrate their
      use. A simulation study reveals that the newly proposed method yields the most
      accurate coverage probabilities under conditions more analogous to practice,
      where assumptions about normally distributed effect size estimates and known
      sampling variances only hold asymptotically.

PMID- 16463356
TI  - Oscillating steady states.
AB  - The signal formation and properties of steady-state free precession (SSFP) in
      combination with alternating RF pulse phases or alternating spin precession is
      analyzed. Simulations and experiments demonstrate that the amplitudes of SSFP
      echo paths are significantly influenced by application of alternating phases
      either via the exciting RF pulse or via some external mechanism producing
      alternating spin precession. The influence of alternating phases on echo
      amplitudes is different for different echo paths. The primary SSFP echo paths
      F(0) (-) and F(0) (+) exhibit a signal reduction whereas higher-order echoes F(
      1) (-) and F(1) (+) show a signal increase upon application of oscillating
      phases. This behavior can be described using a simple perturbation theory applied
      to the frequency response profile of balanced SSFP combined with a final signal
      integration over one balanced SSFP band. The high sensitivity of SSFP echo
      amplitudes to alternating RF pulse phases or precession is exemplarily used to
      detect and visualize propagating transverse acoustic shear waves. Detection of
      flow or alternating currents are further possibilities to apply this unique
      feature of SSFP.

PMID- 16463357
TI  - Feasibility of simultaneous temperature and tissue stiffness detection by MRE.
AB  - Temperature and tissue stiffness are two indices that can be used to monitor MRI
      guided focused ultrasound thermal therapy. It would be beneficial to have both
      measures available to monitor treatment progression during thermal therapy. MR
      Elastography (MRE) has already been shown to provide tissue stiffness
      information; the purpose of this work is to demonstrate how temperature can be
      derived from the same MRE data acquisition. MRE data were acquired from 1.5%
      agarose phantoms and ex vivo porcine muscle tissue (from a grocery store) while
      they were heated slowly. The temperatures were measured using a fluorescent
      thermometer. The phase average from the MRE acquisition was used to calculate the
      phase shift induced by the proton resonance frequency shift associated with the
      temperature change. The results show that the phase shift due to temperature
      extracted from MRE data correlate well with the temperature change recorded by
      thermometer, yielding a temperature coefficient of -0.0096 ppm/ degrees C for the
      agarose phantom, and -0.0103 ppm/ degrees C for the ex vivo porcine tissue. These
      results indicate that it is possible to simultaneously measure both temperature
      and tissue shear stiffness using a new method of MRE data reconstruction.

PMID- 16463358
TI  - Effect of membrane mimicking environment on the conformation of a pore-forming
      (xSxG)6 peptide.
AB  - The mechanism of membrane interaction by beta-sheet peptides is important to
      understand fundamental principles of folding of beta-barrel proteins and various
      beta-amyloid proteins. Here, we examined the conformational characteristics of a
      porin-like channel forming (xSxG)(6) peptide in solution and membrane-mimicking
      environments (CD and ATR-IR) to understand the structural changes of the peptide
      during membrane association and channel formation. A comparison of the peptide
      conformations in different microenvironments showed that beta-sheet formation is
      enhanced in membrane-mimicking liposomes and SDS-micelles. The lipid-induced beta
      sheet formation was confirmed by the formation of a characteristic beta-sheet
      structure on mixing a methanolic solution of the peptide (partially folded) with
      preformed liposomes. The amphipathicity of the peptide; increased hydrogen
      bonding, hydrophilicity, and reduction in dimensionality of the membrane surface;
      membrane-peptide interaction-forces; and presence of flexible glycines might
      facilitate beta-sheet formation in membranes. Though the CD spectra of both the
      peptide-bound and peptide-incorporated lipids are reminiscent of a beta-sheet
      structure, a significant variation in the peak positions of the two beta-sheet
      structures was noticed. The channel characteristics of (xSxG)(6) in the presence
      of low ionic strength solutions of NEt(3)BzCl and glucosammonium chloride are
      comparable to those reported under high ionic strength solutions. Altogether the
      data suggest that the channel formation by (xSxG)(6) proceeds via beta-sheet
      aggregate formation at the membrane surface, beta-sheet insertion, and
      rearrangement into a beta-barrel-like structure. The beta-barrel-like channel
      formation most likely arises from a sequence similarity to beta-barrel porins
      whereas the lipid-induced beta-sheet formation is governed by the above-mentioned
      factors.

PMID- 16463359
TI  - Accurate mass filtering of ion chromatograms for metabolite identification using
      a unit mass resolution liquid chromatography/mass spectrometry system.
AB  - Acceleration of liquid chromatography/mass spectrometric (LC/MS) analysis for
      metabolite identification critically relies on effective data processing since
      the rate of data acquisition is much faster than the rate of data mining. The
      rapid and accurate identification of metabolite peaks from complex LC/MS data is
      a key component to speeding up the process. Current approaches routinely use
      selected ion chromatograms that can suffer severely from matrix effects. This
      paper describes a new method to automatically extract and filter metabolite
      related information from LC/MS data obtained at unit mass resolution in the
      presence of complex biological matrices. This approach is illustrated by LC/MS
      analysis of the metabolites of verapamil from a rat microsome incubation spiked
      with biological matrix (bile). MS data were acquired in profile mode on a unit
      mass resolution triple-quadrupole instrument, externally calibrated using a
      unique procedure that corrects for both mass axis and mass spectral peak shape to
      facilitate metabolite identification with high mass accuracy. Through the double
      filtering effects of accurate mass and isotope profile, conventional extracted
      ion chromatograms corresponding to the parent drug (verapamil at m/z 455),
      demethylated verapamil (m/z 441), and dealkylated verapamil (m/z 291), that
      contained substantial false-positive peaks, were simplified into chromatograms
      that are substantially free from matrix interferences. These filtered
      chromatograms approach what would have been obtained by using a radioactivity
      detector to detect radio-labeled metabolites of interest.

PMID- 16463360
TI  - Orientational order of Australian spider silks as determined by solid-state NMR.
AB  - A simple solid-state NMR method was used to study the structure of (13)C- and
      (15)N-enriched silk from two Australian orb-web spider species, Nephila edulis
      and Argiope keyserlingi. Carbon-13 and (15)N spectra from alanine- or glycine
      labeled oriented dragline silks were acquired with the fiber axis aligned
      parallel or perpendicular to the magnetic field. The fraction of oriented
      component was determined from each amino acid, alanine and glycine, using each
      nucleus independently, and attributed to the ordered crystalline domains in the
      silk. The relative fraction of ordered alanine was found to be higher than the
      fraction of ordered glycine, akin to the observation of alanine-rich domains in
      silk-worm (Bombyx mori) silk. A higher degree of crystallinity was observed in
      the dragline silk of N. edulis compared with A. keyserlingi, which correlates
      with the superior mechanical properties of the former.

PMID- 16463361
TI  - X-ray photoelectron spectroscopic and Raman analysis of silk fibroin-Cu(II)
      films.
AB  - There is evidence to suggest that Cu(II) is involved in the natural spinning
      process of a silkworm helping to convert the concentrated silk fibroin (SF)
      solution (or dope) into tough insoluble threads. To investigate the interaction
      between SF and Cu(II), a series of regenerated SF (RSF) films with different mass
      ratios of Cu(II) to SF were prepared. X-ray photoelectron spectroscopy (XPS) was
      employed to study the chemical interaction between Cu(II) and SF in these Cu(II)
      RSF films. A significant change in the binding energy of Cu 2p(3/2) demonstrated
      that the chemical state of Cu(II) in the Cu(II)-RSF films was affected by the
      interaction between Cu(II) and SF. Moreover, chemical shifts of N 1s and O 1s of
      SF were also detected, implying that Cu(II) may coordinate with both N and O
      atoms in the SF. In addition, Raman spectra of the same series of Cu(II)-RSF
      films recorded the conformation transition of SF that may occur by the
      coordination of Cu(II) and SF macromolecular chains.

PMID- 16463362
TI  - A framework to monitor environment-induced major genes for developmental
      trajectories: implication for a prenatal cocaine exposure study.
AB  - Whether there are specific genes involved in response to different environmental
      agents and how such genes regulate developmental trajectories during lifetime are
      of fundamental importance in health, clinical and pharmaceutical research. In
      this article, we present a novel statistical model for monitoring environment
      induced genes of major effects on longitudinal outcomes of a trait. This model is
      derived within the maximum likelihood framework, incorporated by mathematical
      aspects of growth and developmental processes. A typical structural model is
      implemented to approximate time-dependent covariance matrices for the
      longitudinal trait. This model allows for a number of biologically meaningful
      hypothesis tests regarding the effects of major genes on overall growth
      trajectories or particular stages of development. It can be used to test whether
      and how major genetic effects are expressed differently under altered
      environmental agents. In a well-designed case-control study, our model has been
      employed to detect cocaine-dependent genes that affect growth trajectories for
      head circumference during childhood. The detected gene triggers significant
      effects on growth curves in both cocaine-exposed (case) and unexposed groups
      (control), but with different extents. Significant genotype-environment
      interactions due to this so-called environment-sensitive gene are promising for
      further studies toward its genomic mapping using polymorphic molecular markers.

PMID- 16463363
TI  - Effect of TGF-beta inducible early gene deficiency on flexor tendon healing.
AB  - The role of transforming growth factor beta (TGF-beta) in tendon healing is still
      not clearly established. TGF-beta affects gene expression primarily through the
      activation of the Smad signaling pathway. The first step in the Smad pathway is
      the expression of TGF-beta inducible early gene (TIEG). Recently, a TIEG knockout
      mouse has been developed. The purpose of this study was to examine the healing
      potential of flexor tendons in mice lacking the TIEG gene, and to further examine
      what role the TIEG pathway plays in flexor tendon repair. Twenty-two mice,
      consisting of 11 normal wild-type mice and 11 TIEG knockout mice, were euthanized
      at 8 to 12 weeks of age. The second through fifth FDL tendons of both hind feet
      were transected and repaired in zone 2. The repaired tendons were removed from
      the mice and placed into tissue culture. Tendons were then examined at days 3, 7,
      14, 21, and 42 after surgery. Hematoxylin and eosin (HE) staining and
      immunohistochemical staining for TGF-beta, collagen type I, and collagen type III
      were performed. Reverse transcriptase polymerase chain reaction (RT-PCR) was
      performed to examine expression of TGF-beta1, beta2, beta3, and collagen type I
      and III. At 42 days after surgery, HE staining showed coaptation of lacerated
      tendon ends in both groups. Both groups showed healing of the lacerated tendon,
      but the chronologic expression pattern of TGF-beta was different between the
      knockout and normal tendons. TIEG deficient tendons had delayed expression of TGF
      beta when compared with control tendons. The collagen mRNA expression pattern was
      similar with both groups, but the expression level was different, with TIEG
      knockout tendons having a lower expression of collagen type I mRNA (p < 0.001).
      TGF-beta is thought to play a major role in tendon healing. Healing of tendons in
      the TIEG knockout mouse suggests the possibility of tendon healing in the absence
      of the Smad pathway. The knockout mouse model described in the present study
      provides a novel means for further understanding of the tendon healing process
      through isolated deletion of specific growth factors.

PMID- 16463364
TI  - Shoulder joint position sense improves with elevation angle in a novel,
      unconstrained task.
AB  - Proprioception, encompassing the submodalities of kinesthesia and joint position
      sense, is important in the maintenance of joint stability, especially in the
      shoulder. The purpose of this study was to examine the effects of plane and
      elevation angle on unconstrained shoulder joint position sense. Twenty-two
      subjects (12 male, 10 female) without a history of shoulder pathology were
      recruited from a university campus. Subjects attempted to replicate, with respect
      to plane and elevation angles, various target positions. Target positions
      consisted of five plane angles at 90 degrees of arm elevation and five arm
      elevation angles in the scapular plane. All target positions were tested twice to
      assess the reliability of the measurement. Intraclass correlation coefficients
      were generally low across target positions, possibly owing to the novelty and
      demanding nature of the task. No differences in repositioning errors were
      observed between plane angles (p = 0.255). Repositioning errors decreased
      linearly as the elevation angle increased from 30 degrees to 90 degrees (p =
      0.007) and increased again from 90 degrees to 110 degrees of elevation (p =
      0.029). Our results suggest that unconstrained joint position sense may be
      enhanced with increased muscular activation levels. Further, afferent feedback
      from musculotendinous mechanoreceptors may dominate over that from
      capsuloligamentous sources in unconstrained movements.

PMID- 16463369
TI  - Seventy-Fifth Annual Meeting of the American Association of Physical
      Anthropologists, Anchorage, Alaska, USA, March 8 - 11, 2006. Abstracts.

PMID- 16463365
TI  - Short-term microvascular response of striated muscle to cp-Ti, Ti-6Al-4V, and Ti
      6Al-7Nb.
AB  - Due to excellent mechanical properties and good corrosion resistance, titanium
      aluminium-vanadium (Ti-6Al-4V) and titanium-aluminium-niobium (Ti-6Al-7Nb) are
      extensively used for orthopedic surgery. Concern has been voiced concerning the
      implications of the constituent vanadium in Ti-6Al-4V on the surrounding
      environment. Particularly in osteosynthesis where the alloys stand in direct
      contact to skeletal muscle, undesirable biologic reactions may have severe
      consequences. In a comparative study, we assessed in vivo nutritive perfusion and
      leukocytic response of striated muscle to the metals Ti-6Al-4V, Ti-6Al-7Nb, and
      commercially pure titanium (cpTi), thereby drawing conclusions on their short
      term inflammatory potential. In 28 hamsters, utilizing the dorsal skinfold
      chamber preparation and intravital microscopy, we quantified primary and
      secondary leukocyte-endothelial cell interaction, leukocyte extravasation,
      microvascular diameter change, and capillary perfusion in collecting and
      postcapillary venules of skeletal muscle. A manifest discrepancy between the
      metals concerning impact on local microvascular parameters was not found. All
      metals induced an only transient and moderate inflammatory response. Only a
      slight increase in leukocyte recruitment and a more sluggish recuperation of
      inflammatory parameters in animals treated with Ti-6Al-4V compared to the other
      two metals suggested a minor, overall not significant discrepancy in
      biocompatibility. Gross toxicity of bulk Ti-6Al-4V on surrounding tissue could
      not be found. Conclusively, the commonly used biomaterials Ti-6Al-4V, Ti-6Al-7Nb,
      and cpTi induce an only transient inflammatory answer of the skeletal muscle
      microvascular system. Our results indicate that on the microvascular level the
      tested bulk Ti-alloys and cpTi do not cause adverse biologic reactions in
      striated muscle.

PMID- 16463370
TI  - Ylidic radical-molecule reactions.
AB  - The known reactions between a neutral radical and a neutral closed-shell sigma
      type molecule are generally associated with the atom/group-abstraction (e.g., CN,
      OH reactions) or the carbenoid insertion processes (e.g., CH reactions). In this
      article, we describe a new type of neutral radical-molecule reaction that feature
      the nucleophilic addition and elimination mechanism based on the systematic
      Gaussian-3//MP2(full)/6-31G(d) investigations on the PH(3)CH+HX model reactions
      (X = CH(3), NH(2), OH, F, CH(2)F, CHF(2), CF(3), NHCH(3)/CH(2)NH(2),
      OCH(3)/CH(2)OH). The novel properties are found to benefit both from the radical
      and ylidic characters of PH(3)CH, and the type of reagent HX determines the
      nucleophilic addition reactivity. The present work is the first study on the
      chemical reactivity of the ylidic radicals.

PMID- 16463371
TI  - Computation of hydration free energies of organic solutes with an implicit water
      model.
AB  - A new approach for computing hydration free energies DeltaG(solv) of organic
      solutes is formulated and parameterized. The method combines a conventional PCM
      (polarizable continuum model) computation for the electrostatic component
      DeltaG(el) of DeltaG(solv) and a specially detailed algorithm for treating the
      complementary nonelectrostatic contributions (DeltaG(nel)). The novel features
      include the following: (a) two different cavities are used for treating
      DeltaG(el) and DeltaG(nel). For the latter case the cavity is larger and based on
      thermal atomic radii (i.e., slightly reduced van der Waals radii). (b) The
      cavitation component of DeltaG(nel) is taken to be proportional to the volume of
      the large cavity. (c) In the treatment of van der Waals interactions, all solute
      atoms are counted explicitly. The corresponding interaction energies are computed
      as integrals over the surface of the larger cavity; they are based on Lennard
      Jones (LJ) type potentials for individual solute atoms. The weighting
      coefficients of these LJ terms are considered as fitting parameters. Testing this
      method on a collection of 278 uncharged organic solutes gave satisfactory
      results. The average error (RMSD) between calculated and experimental free energy
      values varies between 0.15 and 0.5 kcal/mol for different classes of solutes. The
      larger deviations found for the case of oxygen compounds are probably due to a
      poor approximation of H-bonding in terms of LJ potentials. For the seven
      compounds with poorest fit to experiment, the error exceeds 1.5 kcal/mol; these
      outlier points were not included in the parameterization procedure. Several
      possible origins of these errors are discussed.

PMID- 16463372
TI  - Vasculogenesis of the embryonic heart: origin of blood island-like structures.
AB  - The earliest vascular structures (blood island-like) in the embryonic heart are
      clusters of angioblasts and nucleated red blood cells (NRBCs), which
      differentiate into endothelial cells and erythrocytes, respectively. Our purpose
      was to define the area and chronology of NRBC appearance in the mouse embryonic
      heart at the stages before a patency between coronary vessels and peripheral
      circulation is established (10.5-13.5 dpc). Before and at the onset of
      vascularization, NBCs were not present within the proepicardium; however,
      Ter/119+ differentiating erythroblasts and single scattered CD45+ were found in
      the heart beginning from 10.5 dpc. The Ter/119+ cells were in close apposition to
      angioblasts (PECAM1+) and were recognized as components of blood island-like
      structures or vascular vesicles in transmission electron microscope and were
      located mostly in the subepicardium. Some of the NRBCs were not accompanied by
      angioblasts and located close to the endocardial endothelium or at the border of
      the endocardial endothelium or in the subepicardium. These erythroblasts were
      beginning to assemble with angioblasts. CD34+ NBCs as well as progenitor cells of
      erythroid lineage were not detected in the heart at these stages of development.
      The state of differentiation of NRBCs of blood islands was similar/the same as
      the morphology of circulating blood cells at the respective stages of embryo
      development. The presence of mature NRBCs in the subendocardial area and lack of
      progenitor cells of erythroid lineage within the heart indicate that erythroid
      commitment occurs outside the heart. We suggest that NRBCs enter the heart from
      the blood stream at 10.5-12 dpc independently from angioblasts.

PMID- 16463373
TI  - Protein distribution of Kcnq1, Kcnh2, and Kcne3 potassium channel subunits during
      mouse embryonic development.
AB  - Voltage-dependent potassium channels consist of a pore-forming alpha-subunit,
      which is modulated by additional beta-ancillary or regulatory subunits. Kcnq1 and
      Kcnh2 alpha-channel subunits play pivotal roles in the developing and adult
      heart. However, Kcnq1 and Kcnh2 have a much wider expression profile than
      strictly confined to the myocardium, similar to their putative regulatory Kcne1-5
      beta-subunits. At present, the distribution of distinct potassium channel
      subunits has been partially mapped in adult tissues, whereas almost no
      information is available during embryonic development. In this study, we report a
      detailed analysis of Kcnq1, Kcnh2, and Kcne3 protein expression during mouse
      embryogenesis. Our results demonstrate that Kcnq1 and Kcnh2 are widely
      distributed. Coexpression of both alpha-subunits is observed in a wide variety of
      organs, such as heart and the skeletal muscle, whereas others display unique
      Kcnq1 or Knch2 expression. Interestingly, Kcne3 expression is also widely
      observed in distinct tissue layers during embryogenesis, supporting the notion
      that an exquisite balance of alpha- and beta-subunit expression is required for
      modulating potassium conductance in distinct organs and tissue layers.

PMID- 16463374
TI  - Deep brain stimulation in Tourette's syndrome: two targets?
AB  - In this report, we describe the effects of bilateral thalamic stimulation in one
      patient and of bilateral pallidal stimulation in another patient. Both patients
      suffered from intractable Tourette's syndrome (TS). Any conservative treatment
      had failed or had been stopped because of unbearable side effects in the 2
      patients. In both cases, there was no comorbidity except for associated
      behavioral symptoms (compulsions). Electrodes were implanted at the level of the
      medial part of the thalamus (centromedian nucleus, the substantia
      periventricularis, and the nucleus ventro-oralis internus) in one patient and in
      the posteroventral part of the globus pallidus internus (GPi) in the other
      patient. In both cases, deep brain stimulation (DBS) resulted in a substantial
      reduction of tics and compulsions. These data show that bilateral DBS of the
      thalamus as well as of the GPi can have a good effect on tics and behavioral
      symptoms in patients suffering from intractable TS.

PMID- 16463375
TI  - Ibuprofen inhibition of tendon cell migration and down-regulation of paxillin
      expression.
AB  - Sports-related tendon injuries are commonly treated with nonsteroidal
      antiinflammatory drugs. Tendon healing requires migration of tendon cells to the
      repair site, followed by proliferation and synthesis of the extracellular matrix.
      This study was designed to determine the effect of ibuprofen on the migration of
      tendon cells intrinsic to rat Achilles tendon. Whether a correlation exits
      between this effect and the expression of paxillin, which is a positive regulator
      of cell spreading and migration, was also investigated. The migration of tendon
      cells was evaluated ex vivo by counting the number of initial outgrowths from the
      tendon explants and in vitro by transwell filter migration assay. The spreading
      of tendon cells in culture was also evaluated microscopically. The mRNA and
      protein expressions of paxillin were determined by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot analysis. Dose-dependent
      ibuprofen inhibition was demonstrated on the migration of tendon cells both ex
      vivo, and in vitro. Similar inhibition was also observed on the spreading of
      tendon cells. Suppression of mRNA expression and protein level of paxillin was
      revealed by RT-PCR and Western blot analyses. The expression of focal adhesion
      kinase (FAK) and tyrosine phosphorylation of FAK remained unchanged. In
      conclusion, ibuprofen inhibits tendon cell migration in a process that is
      probably mediated by the down-regulation of paxillin.

PMID- 16463376
TI  - Phylogenetic memory of developing mammalian dentition.
AB  - Structures suppressed during evolution can be retraced due to atavisms and
      vestiges. Atavism is an exceptional emergence of an ancestral form in a living
      individual. In contrast, ancestral vestige regularly occurs in all members of an
      actual species. We surveyed data about the vestigial and atavistic teeth in
      mammals, updated them by recent findings in mouse and human embryos, and
      discussed their ontogenetic and evolutionary implications. In the mouse incisor
      and diastema regions, dental placodes are transiently distinct being
      morphologically similar to the early tooth primordia in reptiles. Two large
      vestigial buds emerge in front of the prospective first molar and presumably
      correspond to the premolars eliminated during mouse evolution. The incorporation
      of the posterior premolar vestige into the lower first molar illustrates the
      putative mechanism of evolutionary disappearance of the last premolar in the
      mice. In mutant mice, devious development of the ancestral tooth primordia might
      lead to their revivification and origin of atavistic supernumerary teeth.
      Similarity in the developmental schedule between three molars in mice and the
      respective third and fourth deciduous premolar and the first molar in humans
      raises a question about putative homology of these teeth. The complex patterning
      of the vestibular and dental epithelium in human embryos is reminiscent of the
      pattern of "Zahnreihen" in lower vertebrates. A hypothesis was presented about
      the developmental relationship between the structures at the external aspect of
      the dentition in mammals (oral vestibule, pre-lacteal teeth, paramolar
      cusps/teeth), the tooth glands in reptiles, and the earliest teeth in lower
      vertebrates.

PMID- 16463378
TI  - Mitochondrial replication origin stability and propensity of adjacent tRNA genes
      to form putative replication origins increase developmental stability in lizards.
AB  - Secondary structure stability of mitochondrial origins of light-strand
      replication (OL) presumably reduces delayed formation of light-strand initiating
      replication forks on the heavy strand. Delayed replication initiation prolongs
      single strandedness of the heavy strand. More mutations accumulate during the
      prolonged time spent single stranded. Presumably, delayed replication initiation
      and excess mutations affect mitochondrial biochemical processes and ultimately
      morphological outcomes of development at the whole-organism level. This predicts
      that developmental stability increases with OL secondary structure stability and
      with formation of OL-like structures by the five tRNA genes flanking recognized
      OLs. Stable OLs and high percentages of OL-resembling secondary structures of
      adjacent tRNA genes (predicted by Mfold) correlate positively with developmental
      stability in three lizard families (Anguidae, Amphisbaenidae, and Polychrotidae).
      Accounting for effects of the regular OL, Sfold-predicted OL-like propensity of
      the entire tRNA gene cluster (not of individual genes) correlates with increased
      developmental stability in Anguidae, also across the entire free-energy range of
      Boltzmann's distribution of secondary structures. In the fossorial
      Amphisbaenidae, the OL-like structure-forming propensity of tRNA genes correlates
      positively with developmental stability for the distribution's sub-optimally
      stable regions, and negatively for its optimally stable regions, suggesting the
      thermoregulated functioning of OL vs. flanking tRNA genes as replication origins.
      Results for polychrotid tRNA genes are intermediate. Anguid tRNA genes possibly
      function in addition to the regular OL. Mitochondrial tRNA genes may thus
      frequently acquire and lose the alternative OL function, without sequence (gene)
      duplication and loss of their primary function.

PMID- 16463377
TI  - Waking-up the sleeping beauty: recovery of the ancestral bird odontogenic
      program.
AB  - Recent advances in molecular and developmental genetics have provided tools for
      understanding evolutionary changes in the nature of the epithelial-mesenchymal
      interactions regulating the patterned outgrowth of the tooth primordia. Tissue
      recombination experiments in mice have identified the oral epithelium as
      providing the instructive information for the initiation of tooth development.
      Teeth were lost in birds for more than 80 million years ago, but despite their
      disappearance, a number of gene products and the requisite tissue interactions
      needed for tooth formation are found in the avian oral region. It is believed
      that the avian ectomesenchyme has lost the odontogenic capacity, whilst the oral
      epithelium retains the molecular signaling required to induce odontogenesis. In
      order to investigate the odontogenic capacity of the neural crest-derived
      mesenchyme and its potential activation of the avian oral epithelium, we have
      realized mouse neural tube transplantations to chick embryos to replace the
      neural crest cells of chick with those of mouse. Teeth are formed in the
      mouse/chick chimeras, indicating that timing is critical for the acquisition of
      the odontogenic potential by the epithelium and, furthermore, suggesting that
      odontogenesis is initially directed by species-specific mesenchymal signals
      interplaying with common epithelial signals.

PMID- 16463379
TI  - Assessment of the accuracy of dental enamel thickness measurements using
      microfocal X-ray computed tomography.
AB  - Tooth enamel thickness has long been an important character in studies of primate
      and especially hominin phylogeny, taxonomy, and adaptation. Current methods for
      accurately assessing enamel thickness involve the physical sectioning of teeth,
      because measurements of enamel thickness using some radiographic techniques are
      unreliable. However, because destructive methods limit sample sizes and access to
      important fossil specimens, it is desirable that they be replaced with
      nondestructive techniques. Although microfocal X-ray computed tomography (mCT)
      has been used recently in studies of enamel thickness, the accuracy of this
      technique has yet to be established. The present research compares physical
      sections to computer-generated mCT sections of teeth from a variety of primate
      and nonprimate, recent and fossil taxa to examine whether enamel thickness, tooth
      size, and diagenetic remineralization (fossilization) impact the ability of mCT
      to measure enamel thickness accurately. Results indicate that recent teeth of
      varying size and thickness are clearly and accurately depicted in mCT scans, with
      measurements from nearly identical planes in physical and mCT sections differing
      by 3-5%. A fossil papionin molar (ca. 2 Myr) was also accurately measured using
      mCT scans, although thinner enamel in much older therapsid (ca. 263-241 Myr)
      teeth could not be distinguished from dentine. mCT is thus an accurate technique
      for measuring enamel thickness in recent taxa, although heavily mineralized teeth
      pose an obstacle to the ability of mCT to distinguish dental tissues. Moreover,
      absolutely thin enamel (less than approximately 0.10 mm) is difficult to resolve
      adequately in raw mCT images based on pixel values alone. Therefore, caution must
      be exercised in the application of mCT to the study of fossilized teeth.

PMID- 16463380
TI  - Aspects of achondroplasia in the skulls of dwarf transgenic mice: a cephalometric
      study.
AB  - Achondroplasia, the most common short-limbed dwarfism in humans, results from a
      single nucleotide substitution in the gene for fibroblast growth factor receptor
      3 (FGFR3). FGFR3 regulates bone growth in part via the mitogen-activated protein
      kinase pathway (MAPK). To examine the role of this pathway in chondrocyte
      differentiation, a transgenic mouse was generated that expresses a constitutively
      active mutant of MEK1 in chondrocytes and exhibits dwarfing characteristics
      typical of human achondroplasia, i.e., shortened axial and appendicular
      skeletons, mid-facial hypoplasia, and dome-shaped cranium. In this study,
      cephalometrics of the MEK1 mutant skulls were assessed to determine if the MEK1
      mice are a good model of achondroplasia. Skull length, arc of the cranial vault,
      and area, maximum and minimum diameters of the brain case were measured on
      digitized radiographs of skulls of MEK1 and control mice. Cranial base and nasal
      bone length and foramen magnum diameter were measured on midsagittal micro-CT
      sections. Data were normalized by dividing by the cube root of each animal's
      weight. Transgenic mice exhibited a domed skull, deficient midface, and
      (relatively) prognathic mandible and had a shorter cranial base and nasal bone
      than the wild-type. Skull length was significantly less in transgenic mice, but
      cranial arc was significantly greater. The brain case was larger and more
      circular and minimum diameter of the brain case was significantly greater in
      transgenic mice. The foramen magnum was displaced anteriorly but not narrowed.
      MEK1 mouse cephalometrics confirm these mice as a model for achondroplasia,
      demonstrating that the MAP kinase signaling pathway is involved in FGF signaling
      in skeletal development.

PMID- 16463381
TI  - Morphological evidence for existence of IL-6 receptor alpha in the glomus cells
      of rat carotid body.
AB  - The carotid body (CB) senses changes in arterial blood PO2 and modulates
      respiratory movement. It is generally accepted that the dopaminergic type I cells
      in the CB are chemoreceptors. However, it has not been clarified whether the
      carotid body has the ability to perceive the stimulation of proinflammatory
      cytokines. Interleukin 6 (IL-6) as a multifunctional cytokine plays a pivotal
      role in host defense mechanism. In the present study, we observed the expression
      of IL-6Ralpha mRNA and protein in the carotid body using immunohistochemistry,
      Western blots, and in situ hybridization. The results confirmed the presence of
      IL-6Ralpha proteins and mRNAs in the glomus cells of rat carotid body. These
      results suggest that the function of the carotid body may be influenced by the
      proinflammatrory cytokines through their receptors.

PMID- 16463382
TI  - Air pollution and risk of lung cancer in a prospective study in Europe.
AB  - To estimate the relationship between air pollution and lung cancer, a nested case
      control study was set up within EPIC (European Prospective Investigation on
      Cancer and Nutrition). Cases had newly diagnosed lung cancer, accrued after a
      median follow-up of 7 years among the EPIC ex-smokers (since at least 10 years)
      and never smokers. Three controls per case were matched. Matching criteria were
      gender, age (+/-5 years), smoking status, country of recruitment and time elapsed
      between recruitment and diagnosis. We studied residence in proximity of heavy
      traffic roads as an indicator of exposure to air pollution. In addition, exposure
      to air pollutants (NO(2), PM10, SO(2)) was assessed using concentration data from
      monitoring stations in routine air quality monitoring networks. Cotinine was
      measured in plasma. We found a nonsignificant association between lung cancer and
      residence nearby heavy traffic roads (odds ratio = 1.46, 95% confidence interval,
      CI, 0.89-2.40). Exposure data for single pollutants were available for 197 cases
      and 556 matched controls. For NO(2) we found an odds ratio of 1.14 (95% CI, 0.78
      1.67) for each increment of 10 microg/m(3), and an odds ratio of 1.30 (1.02-1.66)
      for concentrations greater than 30 microg/m(3). The association with NO(2) did
      not change after adjustment by cotinine and additional potential confounders,
      including occupational exposures. No clear association was found with other
      pollutants.

PMID- 16463383
TI  - Green tea polyphenol stimulates cancer preventive effects of celecoxib in human
      lung cancer cells by upregulation of GADD153 gene.
AB  - To more clearly understand the molecular mechanisms involved in synergistic
      enhancement of cancer preventive activity with the green tea polyphenol (-)
      epigallocatechin gallate (EGCG), we examined the effects of cotreatment with EGCG
      plus celecoxib, a cyclooxygenase-2 selective inhibitor. We specifically looked
      for induction of apoptosis and expression of apoptosis related genes, with
      emphasis on growth arrest and DNA damage-inducible 153 (GADD153) gene, in human
      lung cancer cell line PC-9: Cotreatment with EGCG plus celecoxib strongly induced
      the expression of both GADD153 mRNA level and protein in PC-9 cells, while
      neither EGCG nor celecoxib alone did. However, cotreatment did not induce
      expression of other apoptosis related genes, p21(WAF1) and GADD45. Judging by
      upregulation of GADD153, only cotreatment with EGCG plus celecoxib
      synergistically induced apoptosis of PC-9 cells. Synergistic effects with the
      combination were also observed in 2 other lung cancer cell lines, A549 and ChaGo
      K-1. Furthermore, EGCG did not enhance GADD153 gene expression or apoptosis
      induction in PC-9 cells in combination with N-(4-hydroxyphenyl)retinamide or with
      aspirin. Thus, upregulation of GADD153 is closely correlated with synergistic
      enhancement of apoptosis with EGCG. Cotreatment also activated the mitogen
      activated protein kinases (MAPKs), such as ERK1/2 and p38 MAPK: Preteatment with
      PD98059 (ERK1/2 inhibitor) and UO126 (selective MEK inhibitor) abrogated both
      upregulation of GADD153 and synergistic induction of apoptosis of PC-9 cells,
      while SB203580 (p38 MAPK inhibitor) did not do so, indicating that GADD153
      expression was mediated through the ERK signaling pathway. These findings
      indicate that high upregulation of GADD153 is a key requirement for cancer
      prevention in combination with EGCG.

PMID- 16463385
TI  - Quantitative comparison of AIR, SPM, and the fully deformable model for atlas
      based segmentation of functional and structural MR images.
AB  - Typical packages used for coregistration in functional image analyses include
      automated image registration (AIR) and statistical parametric mapping (SPM).
      However, both methods have limited-dimension deformation models. A fully
      deformable model, which combines the piecewise linear registration for coarse
      alignment with demons algorithm for voxel-level refinement, allows a higher
      degree of spatial deformation. This leads to a more accurate colocalization of
      the functional signal from different subjects and therefore can produce a more
      reliable group average signal. We quantitatively compared the performance of the
      three different registration approaches through a series of experiments and we
      found that the fully deformable model consistently produces a more accurate
      structural segmentation and a more reliable functional signal colocalization than
      does AIR or SPM.

PMID- 16463386
TI  - ErbB4 increases the proliferation potential of human lung cancer cells and its
      blockage can be used as a target for anti-cancer therapy.
AB  - Clinical and experimental data suggest that ErbB-4, a member of the epidermal
      growth factor receptor family, may have a role in cancer progression and response
      to treatment. We found recently, using a retrospective clinical analysis, that
      expression of ErbB-4 receptor is correlated with metastatic potential and patient
      survival in non-small-cell lung cancer (NSCLC). The purpose of this work was to
      correlate the expression of the ErbB-4 and lung cancer cells growth in vitro and
      in vivo and to determine the therapeutic potential of a monoclonal antibody to
      ErbB-4 against lung cancer. For this aim, we ectopically expressed ErbB-4 in a
      human NSCLC cell line that did not express the ErbB-4 protein. Overexpression of
      ErbB-4 produced a constitutively activated ErbB-4 receptor. The transfected ErbB
      4 positive clones showed an increased cell proliferation in vitro and in vivo in
      comparison with parental ErbB-4 negative cells and with the cells transfected by
      neomycin-resistant gene. A monoclonal antibody to ErbB-4 showed both an
      inhibitory effect on growth rate and an increasing apoptotic rate in the cells
      expressing ErbB-4. The results of the current study provide evidence that ErbB-4
      plays a significant role in human lung cancer and may serve as a molecular target
      for anticancer therapy.

PMID- 16463387
TI  - No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous
      visual discriminations.
AB  - Previous studies have shown that perirhinal cortex lesions in monkeys impair
      visual discriminations with a high degree of "feature ambiguity," a property of
      visual discriminations that can emerge when features are a part of both rewarded
      and unrewarded stimuli. The effects of damage to the hippocampus on these
      perirhinal-dependent feature-ambiguous tasks are, however, unknown. Prominent
      theories of medial temporal lobe function predict similar effects of perirhinal
      cortex and hippocampal lesions on cognitive tasks. In contrast, our hypothesis is
      that perirhinal cortex, and not the hippocampus, is important for nonspatial
      complex feature-ambiguous discriminations. We sought to distinguish between these
      competing theories in a straightforward way, by testing rhesus monkeys with
      hippocampal lesions on the same feature-ambiguous tasks shown previously to
      depend on perirhinal cortex. It was found that hippocampal lesions had no effects
      on any of these tasks. The findings support the perceptual-mnemonic/feature
      conjunction model of perirhinal cortex function, and provide further evidence for
      heterogeneity of function within the putative medial temporal lobe memory system.

PMID- 16463389
TI  - Recent advances in management of patients with platinum-refractory testicular
      germ cell tumors.
AB  - With the use of cisplatin-based combination chemotherapy, metastatic testicular
      germ cell tumors can be cured in 70-80% of patients, but patients refractory to
      cisplatin-based chemotherapy continue to have a very poor prognosis. Various
      chemotherapeutic agents have been evaluated in intensively pretreated or
      cisplatin-refractory patients, but as single agents, only orally administered
      etoposide, paclitaxel, gemcitabine, and, most recently, oxaliplatin have been
      shown to be active with selected patients achieving complete remissions. This has
      for the first time lead to clinical evaluation of combination chemotherapy
      regimens such as gemcitabine-paclitaxel or oxaliplatin-gemcitabine, demonstrating
      the feasibility of combination therapy in these heavily pretreated patients. High
      response rates of up to 45% were observed in particular with the latter
      combination. Salvage surgery remains a very important treatment option for
      patients with resectable disease. The molecular mechanisms of cisplatin
      resistance have been intensively studied, and several mechanisms have been
      discussed such as a decreased intracellular concentration of the drug, increased
      repair of the drug-induced damage, or an altered apoptotic response to this
      damage. This increasing knowledge may now allow design of new therapeutic
      options. Ongoing studies in refractory germ cell tumors are evaluating 3-drug
      regimens such as gemcitabine-paclitaxel-oxaliplatin but also biologic approaches
      such as inhibitors of the epidermal growth factor receptor or the vascular
      endothelial growth factor. This research may eventually allow the development of
      a noncross-resistant multidrug combination regimen that can be evaluated in an
      earlier line of therapy.

PMID- 16463388
TI  - Protein kinase Mzeta enhances excitatory synaptic transmission by increasing the
      number of active postsynaptic AMPA receptors.
AB  - Protein kinase Mzeta (PKMzeta), a constitutively active, atypical PKC isoform,
      enhances synaptic strength during the maintenance of long-term potentiation
      (LTP). Here we examine the mechanism by which PKMzeta increases synaptic
      transmission. Postsynaptic perfusion of PKMzeta during whole-cell recordings of
      CA1 pyramidal cells strongly potentiated the amplitude of AMPA receptor (AMPAR)
      mediated miniature EPSCs (mEPSCs). Nonstationary fluctuation analysis of events
      recorded before and after PKMzeta enhancement showed that the kinase doubled the
      number of functional postsynaptic AMPAR channels. After sustained potentiation,
      application of a PKMzeta inhibitor reversed the increase in functional channel
      number to basal levels, suggesting that persistent increase of PKMzeta is
      required to maintain the postsynaptic localization of a mobile subpopulation of
      receptors. The kinase did not affect other sites of LTP expression, including
      presynaptic transmitter release, silent synapse conversion, or AMPAR unit
      conductance. Thus PKMzeta functions specifically to establish and maintain long
      term increases in active postsynaptic AMPAR number.

PMID- 16463390
TI  - Intratumoral hemorrhage among children with newly diagnosed, diffuse brainstem
      glioma.
AB  - BACKGROUND: Children with diffuse brainstem glioma (BSG) commonly undergo novel
      therapies because their outcome is poor with radiation therapy (RT). Although
      recent clinical trials using new biologic agents documented intratumoral
      hemorrhage (IH) among several children with BSG, to the authors' knowledge little
      is known regarding this phenomenon. In the current study, the authors assessed
      the characteristics and estimated the cumulative incidence of IH among children
      with BSG. METHODS: All available brain imaging studies and medical records of 48
      consecutive patients with newly diagnosed BSG treated at the study institution
      over a 10-year interval (1992-2002) were reviewed. Treatment was comprised of RT
      and various regimens of conventional chemotherapy; none of these patients
      received biologic agents. At the time of last follow-up, all patients had died of
      tumor progression. RESULTS: The authors reviewed 319 imaging studies (251
      magnetic resonance imaging scans and 68 computed tomography scans). IH was
      present in 6.25% of patients at the time of diagnosis. The 6-month and 12-month
      cumulative incidence estimates of IH regardless of the associated symptoms were
      15.5% +/- 5.5% and 24.4% +/- 6.5%, respectively. The same estimates for
      symptomatic cases were 8.9% +/- 4% and 17.8% +/- 6%, respectively. All cases of
      IH at the time of diagnosis and 78% of symptomatic cases that developed after
      diagnosis were located in necrotic areas. CONCLUSIONS: Although IH is uncommon at
      the time of diagnosis, symptomatic IH may occur among nearly 20% of children
      after the diagnosis of BSG. The uniform occurrence of IH among patients treated
      with various chemotherapeutic regimens and its association with necrotic areas
      suggests that tumor biology plays a significant role in this event.

PMID- 16463391
TI  - Staging of chronic myeloid leukemia in the imatinib era: an evaluation of the
      World Health Organization proposal.
AB  - BACKGROUND: Several staging classification systems, all of which were designed in
      the preimatinib era, are used for chronic myeloid leukemia (CML). The World
      Health Organization (WHO) recently proposed a new classification system that has
      not been validated clinically. The authors investigated the significance of the
      WHO classification system and compared it with the classification systems used to
      date in imatinib trials ("standard definition") to determine its impact in
      establishing the outcome of patients after therapy with imatinib. METHODS: In
      total, 809 patients who received imatinib for CML were classified into chronic
      phase (CP), accelerated phase (AP), and blast phase (BP) based on standard
      definitions and then were reclassified according to the new WHO classification
      system. Their outcomes with imatinib therapy were compared, and the value of
      individual components of these classification systems was determined. RESULTS:
      With the WHO classification, 78 patients (10%) were reclassified: 45 patients
      (6%) were reclassified from CP to AP, 14 patients (2%) were reclassified from AP
      to CP, and 19 patients (2%) were reclassified from AP to BP. The rates of
      complete cytogenetic response for patients in CP, AP, and BP according to the
      standard definition were 72%, 45%, and 8%, respectively. After these patients
      were reclassified according to WHO criteria, the response rates were 77% (P =
      0.07), 39% (P = 0.28), and 11% (P = 0.61), respectively. The 3-year survival
      rates were 91%, 65%, and 10%, respectively, according to the standard
      classification and 95% (P = 0.05), 63% (P = 0.76), and 16% (P = 0.18),
      respectively, according to the WHO classification. Patients who had a blast
      percentage of 20-29%, which is considered CML-BP according to the WHO
      classification, had a significantly better response rate (21% vs. 8%; P = 0.11)
      and 3-year survival rate (42% vs. 10%; P = 0.0001) compared with patients who had
      blasts > or = 30%. CONCLUSIONS: Different classification systems had an impact on
      the outcome of patients, and some prognostic features had different prognostic
      implications in the imatinib era. The authors believe that a new, uniform staging
      system for CML is warranted, and they propose such a system.

PMID- 16463392
TI  - Quantifying risks: the case between glucocorticoids and tuberculosis.

PMID- 16463393
TI  - Sustained spontaneous clinical remission in giant cell arteritis: report of two
      cases with long-term followup.

PMID- 16463394
TI  - Churg-Strauss syndrome presenting with salivary gland enlargement and respiratory
      distress.

PMID- 16463396
TI  - Infliximab-related lupus and associated valvulitis: a case report and review of
      the literature.

PMID- 16463398
TI  - Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and
      fluoroethyl SA4503.
AB  - SA4503, a potent sigma(1) receptor agonist, is reported as having 103-fold higher
      affinity for sigma(1) (IC(50) = 17.4 nM) than sigma(2) (IC(50) = 1,784 nM) sites
      in guinea pig brain membranes. Modest structural changes appear to have major
      effects on sigma(1)/sigma(2) selectivity. The fluoroethyl analog, FE-SA4503, is
      described as having high primary affinity for sigma(2) sites (IC(50) = 2.11 nM)
      and a weaker interaction with sigma(1) sites (IC(50) = 6.48 nM). SA4503 and FE
      SA4503 have been radiolabeled for PET studies, and both bind selectively to
      sigma(1) receptors in animal and human brain in vivo. We prepared SA4503 and FE
      SA4503 as reference compounds for radioligand development efforts. In our hands,
      SA4503 is 14-fold selective for sigma(1) (K(i) = 4.6 nM) over sigma(2) (K(i) =
      63.1 nM) sites in guinea pig brain homogenates. Further, FE-SA4503 exhibits the
      same 14-fold selectivity for sigma(1) (K(i) = 8.0 nM) over sigma(2) (K(i) = 113.2
      nM) receptors. The main differences from previously reported values stem from
      sigma(2) affinity determinations. This protocol, displacement of [(3)H]DTG
      binding to sigma(2) sites using (+)-pentazocine (200 nM) to mask sigma(1) sites,
      was validated by the proper rank order of sigma(2) inhibitory potencies shown by
      a panel of additional ligands: ifenprodil > haloperidol > DTG >> (+)-pentazocine.
      Robust Pearson correlation (r = 1.0, P = 0.002; slope = 0.97) was observed for
      our pK(i) values against those from a prior study by others. The findings have
      bearing on structure-activity relationships for this active series, and on
      conclusions that might be drawn from experiments relying upon defined
      sigma(1)/sigma(2) binding selectivity.

PMID- 16463399
TI  - The acute and chronic administration of (+/-)-8-hydroxy-2-(Di-n
      propylamino)tetralin significantly alters the activity of spontaneously active
      midbrain dopamine neurons in rats: an in vivo electrophysiological study.
AB  - This study examined the effect of the acute and chronic systemic administration
      of (+/-)-8-Hydroxy-2-(Di-n-propylamino)Tetralin(8-OH-DPAT) on the number and
      firing pattern of spontaneously active dopamine (DA) neurons in the ventral
      tegmental area (VTA or A10) and substantia nigra pars compacta (SNC or A9) in
      anesthetized male rats. These parameters were measured using extracellular in
      vivo electrophysiology. A single s.c. injection of 0.01, 0.1, or 1 mg/kg of 8-OH
      DPAT did not significantly alter the number of spontaneously active SNC DA
      neurons compared to vehicle-treated animals (controls). The acute administration
      of 0.01 or 0.1 mg/kg of 8-OH-DPAT did not significantly alter, whereas the 1
      mg/kg dose significantly decreased the number of spontaneously active VTA DA
      neurons compared to controls. The acute administration of 8-OH-DPAT significantly
      increased the percentage of VTA DA neurons firing in a bursting pattern. In
      contrast, there was a significant decrease in the percentage of SNC DA neurons
      firing in a bursting pattern following the acute administration of 8-OH-DPAT. The
      number of spontaneously active SNC DA neurons was not significantly altered by
      the chronic s.c. administration of 8-OH-DPAT (0.01, 0.1, or 1 mg/kg s.c.) as
      compared to controls. However, the chronic s.c. administration of all doses of 8
      OH-DPAT significantly decreased the number of spontaneously active VTA DA neurons
      compared to controls. The i.v. administration of (+)-apomorphine (50 microg/kg)
      did not reverse the 8-OH-DPAT-induced decrease in the number of spontaneously
      active VTA DA neurons, suggesting that this effect is unlikely due to
      depolarization blockade. The percentage of VTA DA neurons exhibiting burst firing
      was significantly increased by 0.01 and 0.1 mg/kg, but significantly decreased by
      1 mg/kg of 8-OH-DPAT. Overall, the systemic administration of 8-OH-DPAT
      preferentially affects the activity of spontaneously active A10 DA neurons in
      rats.

PMID- 16463400
TI  - 6-Hydroxydopamine lesions of nucleus accumbens core abolish amphetamine-induced
      conditioned activity.
AB  - Environmental cues associated with drug experiences appear to play a critical
      role in drug dependence. We have previously reported that dopamine-depleting
      lesions of the nucleus accumbens medial shell inhibit amphetamine-conditioned
      place preference. Here, we examined the effects of analogous lesions on
      amphetamine-conditioned locomotor activity. Bilateral core, but not medial shell,
      lesions attenuated unconditioned locomotion and abolished the conditioned
      locomotor response. Taken with our previous results, these findings confirm a
      role for accumbens core in amphetamine-induced locomotor activity and suggest
      that the role of medial shell DA transmission in conditioned place preference is
      related to reward processing rather than conditioning in general.

PMID- 16463401
TI  - In vitro regulation of serotonin transporter activity by protein kinase A and
      nicotinic acetylcholine receptors in the prefrontal cortex of rats.
AB  - We investigated the effect of in vitro exposure to nicotinic acetylcholine
      receptors (nAChRs), agonists, antagonists, and protein kinase A (PKA) modulators
      on the activity of the serotonin transporter (SERT) in prefrontocortical (PFC)
      synaptosomes. The plasma membrane SERT is an active transport mechanism specific
      for serotonin. Receptors and second messengers capable of altering transporter
      activity would be expected to have profound effects on serotonergic
      neurotransmission and on functions involving serotonergic input, such as
      cognition, anxiety, and mood. Our data suggest that activation of nAChRs, quite
      likely via PKA, increase the activity of the SERT in the PFC and, thereby, can
      alter 5-HT levels in a region important in the behavioral effects of nicotine and
      5-HT. Nicotine at 4 microM increased [(3)H]5-HT uptake by 75%. Because the nAChR
      antagonists mecamylamine and dihydro-beta-erythrodine (DHbetaE) both decreased
      [(3)H]5-HT uptake into synaptosomes, it appeared that the SERT might be tonically
      activated by acetylcholine present within our synaptosomal preparations. Blocking
      PKA significantly decreased [(3)H]5-HT, while stimulation of PKA activity
      significantly increased the uptake. A 66% decrease compared with control was
      produced by 100 microM Rp-cAMP, and a 41% increase in 5-HT uptake over control
      was observed with 30 microM Sp-cAMPs. Furthermore, the enhancement in uptake
      produced by 4 microM nicotine was inhibited in a time-dependent fashion by
      preincubation with 10 microM Rp-cAMP. A better understanding of the influence of
      the cholinergic system and the receptors involved in the trafficking of SERT
      would help clarify the important relationship between the cholinergic and
      serotonergic systems and the role these systems play in behavior.

PMID- 16463402
TI  - Cellular features of endometrial hyperplasia and well differentiated
      adenocarcinoma using the Endocyte sampler: Diagnostic criteria based on the
      cytoarchitecture of tissue fragments.
AB  - BACKGROUND: Because cellular atypia is often limited in endometrial hyperplasia
      and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma),
      diagnostic criteria for endometrial cytology have not been fully established. New
      diagnostic criteria based on the composition and architecture of tissue fragments
      (cytoarchitecture) in the smears were used in the present study. Cytologic
      features are of less importance because the distinction between endometrial
      hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than
      cellular changes. Cell clumps of various size are usually collected abundantly
      with cytologic material using a disposable scraping device and it was noticed
      that those cell clumps reflected the histologic architecture. The purpose of the
      current study was to determine the form of the cytoarchitecture that reflects the
      histologic structure and to examine the cellular features in endometrial
      hyperplasia and Grade 1 adenocarcinoma. METHODS: The frequency of each type of
      cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular
      protrusion, and papillotubular pattern) were obtained from 49 cases of normal
      proliferative endometrium (NPE) (patient age range, 28-51 yrs; average age, 39.9
      yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range,
      35-65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with
      atypia (AEH) (patient age range 47-65 yrs; average age, 53.8 yrs), and 49 cases
      of Grade 1 adenocarcinoma (patient age range, 42-73 yrs; average age, 58.9 yrs).
      RESULTS: Certain characteristics of the cytoarchitecture were observed. In the
      NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of
      cases. In the EH, cell clumps with a dilated or branched pattern were found in
      34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular
      protrusions were found in 61.8% cases, whereas a papillotubular pattern was
      present in 29.7% of cases. CONCLUSIONS: The results of the current study revealed
      that cytoarchitectural criteria appear to be more useful for the cytologic
      assessment of endometrial lesions, especially for the diagnosis of endometrial
      hyperplasia and Grade 1 adenocarcinoma.

PMID- 16463403
TI  - A Food and Drug Administration primer.

PMID- 16463404
TI  - Approval process and access to prescription drugs in Canada.

PMID- 16463405
TI  - Drug evaluation and approval process in the European Union.

PMID- 16463406
TI  - Role of RANK ligand in normal and pathologic bone remodeling and the therapeutic
      potential of novel inhibitory molecules in musculoskeletal diseases.
AB  - This is the first article in a new series entitled "Clinical Aspects of Molecular
      Research in Rheumatology," which will appear regularly in Arthritis Care &
      Research. As with all health care professionals, our readership is increasingly
      faced with the reality that in medicine today there is simply "too much to know."
      This is particularly true for those confronted by the challenges of interpreting
      the remarkable advances occurring in the fields of cellular and molecular biology
      as applied to research in rheumatology. This series will present concise reviews
      written by leaders in the field that are tailored to non-laboratory-based
      readers. It is hoped that these articles will provide both an overview of cutting
      edge science in an interpretable format, and provide direction for those desiring
      to learn more about the precise topics. We welcome reader feedback and ideas for
      future topics.

PMID- 16463407
TI  - Glucocorticoid use, other associated factors, and the risk of tuberculosis.
AB  - OBJECTIVE: To evaluate the association of glucocorticoids and other purported
      risk factors with the development of tuberculosis. METHODS: We conducted a case
      control study of tuberculosis cases identified during 1990-2001 using the General
      Practice Research Database in the United Kingdom. Cases were patients with a
      first time diagnosis of tuberculosis accompanied by at least 6 months of
      treatment with at least 3 different tuberculosis medications. Up to 4 controls
      were matched to each case on age, sex, the practice attended by the case, index
      date, and amount of prior computerized records. RESULTS: The study encompassed
      497 new cases of tuberculosis and 1,966 controls derived from 16,629,041 person
      years at risk (n = 2,757,084 persons). The adjusted odds ratio (OR) of
      tuberculosis for current use of a glucocorticoid compared with no use was 4.9
      (95% confidence interval [95% CI] 2.9-8.3). The adjusted ORs for use of <15 mg
      and > or =15 mg of prednisone or its equivalent daily dose were 2.8 (95% CI 1.0
      7.9) and 7.7 (95% CI 2.8-21.4), respectively. Adjusted ORs of tuberculosis were
      2.8 for patients with a body mass index (BMI) <20 compared with normal BMI; 1.6
      for current smokers compared with nonsmokers; and 3.8, 3.2, 2.0, and 1.4 for
      those with history of diabetes, emphysema, bronchitis, and asthma, respectively,
      compared with those without such history (all P values <0.05). CONCLUSION: These
      results indicate that patients treated with glucocorticoids have an increased
      risk of developing tuberculosis, independent of other risk factors. Low
      adiposity, diabetes, current smoking, and obstructive pulmonary disorders are
      also important independent risk factors for tuberculosis.

PMID- 16463408
TI  - Retrospective analysis of utilization patterns and cost implications of coxibs
      among seniors in Quebec, Canada: what is the potential impact of the withdrawal
      of rofecoxib?
AB  - OBJECTIVE: In September 2004, the manufacturer of rofecoxib announced a voluntary
      worldwide withdrawal of the drug. The impact of this withdrawal on drug budgets
      is unclear. This study evaluated average daily doses and costs of rofecoxib and
      celecoxib and concomitant use of gastroprotective agents (GPAs) in elderly
      patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in Quebec, prior
      to the rofecoxib withdrawal. METHODS: This retrospective cohort study used
      prescription drug and medical service data from the Quebec government health
      agency administrative database and included coxib users > or =66 years of age
      with OA or RA who filled > or =3 consecutive rofecoxib or celecoxib prescriptions
      in 2001-2002. Results were adjusted for gastrointestinal risk factors and other
      patient baseline characteristics. RESULTS: Data were analyzed for 11,975
      rofecoxib and 12,480 celecoxib users. Mean daily dosages were 20.7 mg for
      rofecoxib and 231.3 mg for celecoxib. Rofecoxib users consumed a mean +/- SD of
      0.95 +/- 0.43 pills per day, and celecoxib users took 1.34 +/- 0.65 pills per
      day. Mean +/- SD unadjusted daily acquisition costs were $1.18 +/- $0.53
      (Canadian) for rofecoxib and $1.45 +/- $0.74 for celecoxib. After adjusting for
      patient baseline characteristics, the mean daily acquisition cost for rofecoxib
      was $0.25 lower than for celecoxib. Rofecoxib users were less likely than
      celecoxib users to fill a GPA coprescription (odds ratio 0.88; 95% confidence
      interval 0.81, 0.95). Subgroup analyses yielded comparable results. CONCLUSION:
      Celecoxib appears to be a more expensive therapeutic option than rofecoxib due to
      a relatively higher daily dose and tablet consumption.

PMID- 16463409
TI  - Prescription opioid use among older adults with arthritis or low back pain.
AB  - OBJECTIVE: To examine patterns of chronic opioid use in selected groups with
      arthritis and low back pain and compare them with patterns among persons with
      ischemic heart disease. METHODS: The study database consisted of Medicare
      beneficiaries who were enrolled in a drug benefit program for low-to-moderate
      income Pennsylvania residents. We identified selected patients who had a
      diagnosis of rheumatoid arthritis, osteoarthritis, chronic low back pain, or
      ischemic heart disease since 1995. Chronic opioid use, defined as at least six 30
      day prescriptions in a year, was the endpoint of interest. We examined the
      proportion of patients meeting this definition during the period 1996-2001 and
      determined predictors based on multivariable Cox proportional hazards models.
      RESULTS: Four percent of subjects with rheumatoid arthritis used opioids
      chronically in 2001, compared with <1% in each of the other groups. There was no
      increase in the chronic use of opioids over the 6-year study period. Low-potency
      opioids were the most commonly prescribed preparations for chronic users from all
      patient groups. The prior use of medicines for psychiatric illness, including
      benzodiazepines or barbiturates, was associated with chronic prescription opioid
      use across all diagnoses. However, subjects with a prior diagnosis of psychiatric
      illness were less likely to receive chronic opioids. CONCLUSION: Chronic opioid
      use is relatively uncommon, even among older individuals with arthritis or low
      back pain. The proportion of these individuals receiving such medicines has not
      increased in the late 1990s. There seems to be a complex relationship between
      psychiatric medication use, psychiatric diagnoses, and the use of chronic opioids
      among these individuals.

PMID- 16463410
TI  - Effectiveness of the primary therapist model for rheumatoid arthritis
      rehabilitation: a randomized controlled trial.
AB  - OBJECTIVE: To compare the primary therapist model (PTM), provided by a single
      rheumatology-trained primary therapist, with the traditional treatment model
      (TTM), provided by a physical therapy (PT) and/or occupational therapy (OT)
      generalist, for treating patients with rheumatoid arthritis (RA). METHODS:
      Eligible patients were adults requiring rehabilitation treatment who had not
      received PT/OT in the past 2 years. Participants were randomized to the PTM or
      TTM group. The primary outcome was defined as the proportion of clinical
      responders who experienced a > or =20% improvement in 2 of the following measures
      from baseline to 6 months: Health Assessment Questionnaire, pain visual analog
      scale, and Arthritis Community Research and Evaluation Unit RA Knowledge
      Questionnaire. RESULTS: Of 144 consenting patients, 33 (10 PTM participants, 23
      TTM participants) dropped out without completing any followup assessment, leaving
      111 for analysis (63 PTM participants, 48 TTM participants). The majority were
      women (PTM 87.3%, TTM 79.2%), with a mean age of 54.2 years and 56.8 years for
      the PTM and TTM groups, respectively. Average disease duration was 10.6 years and
      13.2 years for each group, respectively. At 6 months, 44.4% of patients in the
      PTM group were clinical responders versus 18.8% in the TTM group (chi(2) = 8.09,
      P = 0.004). CONCLUSION: Compared with the TTM, the PTM was associated with better
      outcomes in patients with RA. The results, however, should be interpreted with
      caution due to the high dropout rate in the TTM group.

PMID- 16463411
TI  - Profile of arthritis disability: II.
AB  - OBJECTIVE: Arthritis is the most common chronic condition and the most common
      cause of disability among older US adults. We studied social participation,
      disabilities in many life domains, accommodations used (buffers), and
      accommodations needed (barriers) for US adults with arthritis disability compared
      with adults with disability from other conditions. METHODS: The data source is
      the National Health Interview Survey Disability Supplement Phase Two. Arthritis
      disabled individuals named arthritis as the main cause of > or =1 disabilities.
      Other-disabled individuals named only other conditions as causes of their
      disabilities. We compared outcomes for the groups, taking sample weights and
      complex variances into account. RESULTS: Arthritis-disabled individuals get out
      and about less often than other-disabled individuals, but they manage to maintain
      active social ties. They have more disabilities of all types (personal care,
      household management, physical tasks, transportation, home, work), and the
      disabilities often cause fatigue, long task time, and pain. Despite this,
      arthritis-disabled individuals use less personal assistance than other-disabled
      individuals; they do use more equipment assistance. Arthritis-disabled
      individuals report more barriers in getting around outside their home and at
      their workplace. CONCLUSION: The distinctive profile of arthritis disability
      includes extensive and uncomfortable disabilities, yet there are active
      management strategies to handle these disabilities. Problems away from home and
      at work should inspire engineers and planners to improve public access and
      equipment for persons with this high-prevalence disability.

PMID- 16463412
TI  - Synovial fluid levels of anti-cyclic citrullinated peptide antibodies and IgA
      rheumatoid factor in rheumatoid arthritis, psoriatic arthritis, and
      osteoarthritis.
AB  - OBJECTIVE: To assess the levels of anti-cyclic citrullinated peptide (anti-CCP)
      and IgA rheumatoid factor (IgA-RF) in synovial fluids of patients with rheumatoid
      arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA). METHODS: Knee
      effusions of 29 patients with RA (23 women, 6 men; mean +/- SD age 60 +/- 15
      years), 20 with PsA (6 women, 14 men; mean age 51 +/- 12 years), and 19 with OA
      (9 women, 10 men; mean age 73 +/- 11.8 years) were aspirated, tested for white
      blood cell (WBC) counts, centrifuged, and stored at -20 degrees . Sera of 22, 11,
      and 12 of these patients with RA, PsA, and OA, respectively, were similarly
      stored. IgG anti-CCP and IgA-RF were detected by enzyme-linked immunosorbent
      assay. Erythrocyte sedimentation rate and C-reactive protein levels were used as
      measures of disease activity. RESULTS: Mean levels of synovial fluid anti-CCP and
      IgA-RF were significantly increased in RA joint effusions compared with PsA and
      OA (anti-CCP: 150 +/- 134, 34 +/- 29, and 24 +/- 26 units, respectively [P <
      0.003]; IgA-RF: 76 +/- 77, 15.7 +/- 10, and 18 +/- 20 units, respectively). No
      significant difference was noted between OA and PsA. A significant correlation
      was found between synovial fluid anti-CCP and serum anti-CCP and IgA-RF. In
      patients with RA, a significant correlation was found between synovial fluid WBC
      counts and IgA-RF (P = 0.03) and serum IgA-RF (P = 0.008), but not between
      synovial fluid and serum anti-CCP levels. In RA patients, C-reactive protein
      correlated with serum IgA-RF. CONCLUSION: Anti-CCP and IgA-RF were significantly
      increased in synovial fluid of RA in comparison with PsA and OA patients.

PMID- 16463413
TI  - Mutational screening of the CYP26A1 gene in patients with caudal regression
      syndrome.
AB  - BACKGROUND: The retinoic acid (RA)-catabolizing enzyme Cyp26a1 plays an important
      role in protecting tailbud tissues from inappropriate exposure to RA. Cyp26a1
      null animals exhibit caudal agenesis and spina bifida, imperforate anus, agenesis
      of the caudal portions of the digestive and urogenital tracts, and malformed
      lumbosacral skeletal elements. This phenotype closely resembles the most severe
      form of caudal agenesis in humans. In view of these findings, we investigated a
      potential involvement of the human CYP26A1 gene in the pathogenesis of caudal
      regression syndrome (CRS). METHODS: Mutational screening of 49 CRS patients and
      132 controls was performed using denaturing high-performance liquid
      chromatography and sequencing. Differences in the genotype and allele frequency
      of each SNP were evaluated by chi(2) analysis. The biological significance of the
      intronic variants was investigated by transfection assays of mutant constructs
      and by analysis of the splicing patterns with RT-PCR. RESULTS: Mutational
      screening allowed us to identify 6 SNPs, 4 of which (447 C>G, 1134 G>A, IVS 1+10
      G>C, and IVS 4+8 AG>GA) are new. In addition, we describe a novel 2-site
      haplotype consisting of the 2 intronic SNPs. Both single-locus and haplotype
      analyses revealed no association with increased risk for CRS. The consequences of
      the 2 intronic polymorphisms on the mRNA splicing process were also investigated.
      Moreover, using functional and computational methods we demonstrated that both of
      these intronic polymorphisms affect the intron splicing efficiency. CONCLUSIONS:
      Our research did not provide evidence that CYP26A1 has implications for the
      pathogenesis of human CRS. However, the relationship between CRS risk and the
      CYP26A1 genotype requires further study with a larger number of genotyped
      subjects.

PMID- 16463414
TI  - A randomized controlled trial of deep water running: clinical effectiveness of
      aquatic exercise to treat fibromyalgia.
AB  - OBJECTIVE: To compare the clinical effectiveness of aerobic exercise in the water
      with walking/jogging for women with fibromyalgia (FM). METHODS: Sixty sedentary
      women with FM, ages 18-60 years, were randomly assigned to either deep water
      running (DWR) or land-based exercises (LBE). Patients were trained for 15 weeks
      at their anaerobic threshold. Visual analog scale of pain, Fibromyalgia Impact
      Questionnaire (FIQ), Beck Depression Inventory, Short Form 36 Health Survey (SF
      36), and a patient's global assessment of response to therapy (PGART) were
      measured at baseline, week 8, and week 15. Statistical analysis included all
      patients. RESULTS: Four patients dropped out from each group. Both groups
      improved significantly at week 15 compared with baseline, with an average 36%
      reduction in pain intensity. For PGART, 40% of the DWR group and 30% of the LBE
      group answered "much better" at posttreatment. FIQ total score and FIQ depression
      improvements in the DWR group were faster (week 8) than the LBE group and kept
      improving (week 15; P < 0.05). Only the DWR group showed improvements in SF-36
      role emotional (P = 0.006). No significant between-group differences were
      observed for peak oxygen uptake and other outcomes. CONCLUSION: DWR is a safe
      exercise that has been shown to be as effective as LBE regarding pain. However,
      it has been shown to bring more advantages related to emotional aspects. Aerobic
      gain was similar for both groups, regardless of symptom improvement. Therefore,
      DWR could be studied as an exercise option for patients with FM who have problems
      adapting to LBE or lower limbs limitations.

PMID- 16463416
TI  - Short-term prediction of mortality in patients with systemic lupus erythematosus:
      classification of outcomes using random forests.
AB  - OBJECTIVE: To identify demographic and clinical characteristics that classify
      patients with systemic lupus erythematosus (SLE) at risk for in-hospital
      mortality. METHODS: Patients hospitalized in California from 1996 to 2000 with a
      principal diagnosis of SLE (N = 3,839) were identified from a state
      hospitalization database. As candidate predictors of mortality, we used patient
      demographic characteristics; the presence or absence of 40 different clinical
      conditions listed among the discharge diagnoses; and 2 summary indexes derived
      from the discharge diagnoses, the Charlson Index and the SLE Comorbidity Index.
      Predictors of patients at increased risk of mortality were identified and
      validated using random forests, a statistical procedure that is a generalization
      of single classification trees. Random forests use bootstrapped samples of
      patients and randomly selected subsets of predictors to create individual
      classification trees, and this process is repeated to generate multiple trees (a
      forest). Classification is then done by majority vote across all trees. RESULTS:
      Of the 3,839 patients, 109 died during hospitalization. Selecting from all
      available predictors, the random forests had excellent predictive accuracy for
      classification of death. The mean classification error rate, averaged over 10
      forests of 500 trees each, was 11.9%. The most important predictors were the
      Charlson Index, respiratory failure, SLE Comorbidity Index, age, sepsis,
      nephritis, and thrombocytopenia. CONCLUSION: Information on clinical diagnoses
      can be used to accurately predict mortality among hospitalized patients with SLE.
      Random forests represent a useful technique to identify the most important
      predictors from a larger (often much larger) number and to validate the
      classification.

PMID- 16463415
TI  - Exercise in waist-high warm water decreases pain and improves health-related
      quality of life and strength in the lower extremities in women with fibromyalgia.
AB  - OBJECTIVE: To evaluate the short- and long-term efficacy of exercise therapy in a
      warm, waist-high pool in women with fibromyalgia. METHODS: Thirty-four women
      (mean +/- SD tender points 17 +/- 1) were randomly assigned to either an exercise
      group (n = 17) to perform 3 weekly sessions of training including aerobic,
      proprioceptive, and strengthening exercises during 12 weeks, or to a control
      group (n = 17). Maximal unilateral isokinetic strength was measured in the knee
      extensors and flexors in concentric and eccentric actions at 60 degrees /second
      and 210 degrees /second, and in the shoulder abductors and adductors in
      concentric contractions. Health-related quality of life (HRQOL) was assessed
      using the EQ-5D questionnaire; pain was assessed on a visual analog scale. All
      were measured at baseline, posttreatment, and after 6 months. RESULTS: The
      strength of the knee extensors in concentric actions increased by 20% in both
      limbs after the training period, and these improvements were maintained after the
      de-training period in the exercise group. The strength of other muscle actions
      measured did not change. HRQOL improved by 93% (P = 0.007) and pain was reduced
      by 29% (P = 0.012) in the exercise group during the training, but pain returned
      close to the pretraining level during the subsequent de-training. However, there
      were no changes in the control group during the entire period. CONCLUSION: The
      therapy relieved pain and improved HRQOL and muscle strength in the lower limbs
      at low velocity in patients with initial low muscle strength and high number of
      tender points. Most of these improvements were maintained long term.

PMID- 16463417
TI  - Treatment of pain in juvenile idiopathic arthritis: a survey of pediatric
      rheumatologists.
AB  - OBJECTIVE: To assess the opinions and current practice of pediatric
      rheumatologists regarding treatment of chronic pain in children with juvenile
      idiopathic arthritis (JIA). METHODS: Standardized questionnaires were distributed
      to pediatric rheumatologists who are members of the Children's Arthritis and
      Rheumatology Research Alliance. Demographic data, opinions, and attitudes were
      solicited about pain assessment, current treatment of JIA with residual pain, and
      actual use of opioids to treat pain in children with JIA. RESULTS: Of 99
      rheumatologists who were contacted, 53 responses were received (53.5%). No
      significant demographic differences were found in attitudes about pain management
      and use of opioids. A total of 77.3% of respondents agreed that there are
      patients who continue to have significant pain despite adequate treatment.
      However, 59.6% disagreed with the use of opioid analgesics for treatment of those
      patients. Cross tabulations showed significant relationships between attitudes
      about opioid use and concerns for side effects, including drowsiness, fatigue,
      and constipation (chi(2) = 1.16, P > 0.05), as well as addiction (chi(2) = 5.51,
      P = 0.019). Thirty percent of those who strongly disagreed with opioid use and
      52.4% of those who disagreed had in fact prescribed opioids in the past year. The
      most commonly prescribed opioids were codeine and oxycodone. Practitioners'
      perceived knowledge of the drugs significantly affected their likelihood to
      prescribe them. CONCLUSION: Pediatric rheumatologists are divided in their
      attitudes regarding treatment of residual pain in children with JIA. Concern for
      side effects appears to be a major factor in the decision to prescribe these
      analgesics. More data are needed to facilitate clearer cost-benefit analyses in
      the decision to prescribe opioids to this clinical population.

PMID- 16463418
TI  - Illness uncertainty, partner caregiver burden and support, and relationship
      satisfaction in fibromyalgia and osteoarthritis patients.
AB  - OBJECTIVE: Fibromyalgia syndrome (FMS) is characterized by uncertainty in
      diagnosis, treatment, and outcome. This study assessed the role of uncertainty of
      illness in relationship satisfaction in patients with FMS and osteoarthritis
      (OA). METHODS: A total of 51 patients with FMS responded to self-report
      instruments assessing their uncertainty about their illness, functional ability,
      average pain, and relationship satisfaction. Their partners independently
      reported on their sense of caregiver burden and their supportiveness toward the
      patients. Thirty-two patients with OA and their partners served as a control
      group. RESULTS: Patients' functional ability and pain were related to partner
      caregiver burden. Partner caregiver burden was related to lower levels of partner
      supportiveness for the FMS dyads, but not for the OA dyads. Relationship
      satisfaction of patients with FMS was related to their higher levels of
      uncertainty of illness in interaction with their functional disability and pain
      and their partners' supportiveness. Under high levels of uncertainty of illness,
      low levels of partner supportiveness were related to lower patient relationship
      satisfaction, whereas low levels of uncertainty of illness were significant
      interacting variables in the OA sample. CONCLUSION: The results suggest that
      uncertainty of illness is a prominent feature affecting patients with FMS in
      their relationships with their partners. Suggestions for additional research to
      explore the role of uncertainty of illness in social relationships are presented,
      and the therapeutic implications for patient/partner relationships are explored.

PMID- 16463419
TI  - Determinants of self efficacy for physical tasks in people with knee
      osteoarthritis.
AB  - OBJECTIVE: Self efficacy, the confidence an individual has to perform a task, is
      an important determinant of physical performance in individuals with knee
      osteoarthritis (OA). The purpose of this study was to determine what personal,
      pathophysiologic, and impairment factors relate to self efficacy for physical
      tasks in community-dwelling adults with knee OA. METHODS: Fifty-four persons with
      radiographically confirmed knee OA (mean +/- SD age 68.3 +/- 8.7 years, range 50
      87 years) participated. The Functional Self-Efficacy subscale of the Arthritis
      Self-Efficacy Scale was the dependent measure. Independent measures included age,
      education, scores from the Center for Epidemiologic Studies Depression and State
      Trait Anxiety Inventory questionnaires, medial joint space and varus/valgus
      tibiofemoral angle from radiographs, body mass index, and isokinetic quadriceps
      and hamstrings strength. Knee pain and stiffness, assessed using the Western
      Ontario and McMaster Universities Osteoarthritis Index, were independent
      measures. RESULTS: Fifty-one percent of the variance of Functional Self Efficacy
      was explained by knee stiffness, hamstrings strength, age, and depression scores.
      Pain, education, anxiety, radiographic joint space, and body weight did not
      significantly contribute to the variance in Functional Self-Efficacy scores.
      Substituting quadriceps strength for hamstrings strength resulted in a regression
      model that included only stiffness, age, and depression, which explained nearly
      as much variance as the original model. CONCLUSION: Self efficacy for physical
      tasks is related to the sensation of stiffness, hamstrings strength, age, and
      level of depressive symptoms in persons with knee OA. Clinicians and researchers
      could consider these variables when assessing the level of self efficacy for
      physical tasks in persons with knee OA.

PMID- 16463420
TI  - Cleidocranial dysplasia with severe parietal bone dysplasia: C-terminal RUNX2
      mutations.
AB  - BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal-dominant skeletal
      dysplasia syndrome that is characterized by widely patent calvarial sutures,
      clavicular hypoplasia, supernumerary teeth, and short stature. CCD is caused by
      mutations in the transcription factor RUNX2, which is known to function as a
      major regulator of bone differentiation. Despite the characterization of 67
      unique mutations in 97 individual cases, and the availability of animal models,
      no obvious genotype-phenotype correlation has emerged. METHODS: We describe 3 new
      cases that were ascertained on the basis of a severe calvarial phenotype, that
      were associated with 3 novel mutations in the C-terminal region of RUNX2 distal
      to the DNA-binding runt domain. In addition, a review of all previously described
      cases was undertaken in an effort to standardize mutation nomenclature,
      characterize the position of known mutations relative to the runt domain, and
      explore the hypothesis that C-terminal mutations that preserve the runt domain
      may lead to more-severe craniofacial phenotypes. RESULTS: Upon mutational
      analysis of RUNX2, we identified either frameshift or splice-site mutations that
      affect the C-terminal region of the resultant protein distal to the runt domain.
      CONCLUSIONS: In the context of previously described mutations, these cases
      suggest that C-terminal mutations that preserve the DNA-binding runt domain while
      disrupting the SMAD 1,2,3,5 binding domain and the nuclear matrix targeting
      signal may be responsible for the severe phenotype observed.

PMID- 16463421
TI  - Differential teratogenesis of all-trans-retinoic acid administered on gestational
      day 9.5 to SWV and C57BL/6N mice: emphasis on limb dysmorphology.
AB  - BACKGROUND: Mouse strain differences in teratologic response are well documented.
      However, because retinoids cause similar malformation syndromes across many
      species, the strain differences may be predicted to be minimal. The goals of this
      study were to characterize and explain the differences between the C57BL/6N and
      SWV mouse strains in terms of all-trans-retinoic acid (RA)-induced teratologic
      effects at the time of gestation that cause postaxial forelimb ectrodactyly.
      METHODS: Visceral and skeletal malformations were determined by Wilson's
      sectioning and double-staining techniques, respectively; developmental staging
      was performed according to the somite count; and retinoid concentrations were
      assessed by HPLC. RESULTS: C57BL/6N mice were more susceptible than SWV mice to
      induction of embryolethality, cardiovascular defects, and forelimb ectrodactyly,
      whereas the opposite was true for the induction of ear, thymus, and tail
      agenesis, and cleft palate, gastroschisis, and anal atresia. As determined by
      somite counts, 1 strain intercross was developmentally advanced compared to the
      parental strains and the reciprocal cross. Retinoid susceptibility was equivalent
      between the reciprocal crosses for some malformations and determined by the
      maternal genotype for others. Toxicokinetic experiments showed that whole-embryo
      peak retinoid concentrations did not differ between the strains, but the area
      under the curve (AUC) for all-trans-RA was 1.3 times higher in C57BL/6N than in
      SWV embryos. CONCLUSIONS: The malformation spectrum induced by RA was strain
      specific, and the strain sensitivity for forelimb ectrodactyly was consistent
      with all previously tested teratogenic agents (i.e., C57BL/6N was more sensitive
      than SWV). The strain differences in teratologic effects were not explained by
      developmental timing differences or toxicokinetic differences at the whole-embryo
      level.

PMID- 16463422
TI  - Functional index-2: Validity and reliability of a disease-specific measure of
      impairment in patients with polymyositis and dermatomyositis.
AB  - OBJECTIVE: To revise the content of the Functional Index in myositis (FI) and to
      evaluate measurement properties of a revised FI. METHODS: Previously performed FI
      (n = 287) were analyzed for internal redundancy and consistency, and ceiling and
      floor effects. Content was evaluated and a preliminary revised FI was developed.
      To evaluate the construct validity of the preliminary revised FI, it was compared
      with isokinetic measurements of muscular strength and endurance, the Myositis
      Activities Profile, disease impact on general wellbeing, and creatine
      phosphokinase levels. Minor adjustments were made and the revised FI was
      investigated for interrater reliability and intrarater reliability over a 1-week
      period. After this, some minor, additional adjustments were made leading to the
      final version, FI-2. RESULTS: Five tasks were removed from the original FI due to
      ceiling effects. Performance pace and number of repetitions were modified for the
      remaining tasks. A moderate correlation (r(s) = 0.58) was found between the
      shoulder flexion task of the preliminary revised FI and isokinetic measurements
      of shoulder flexion endurance. Intraclass correlation coefficient (ICC) for
      interrater reliability of the revised FI varied from 0.86-0.99 with no systematic
      differences. ICC for intrarater reliability varied from 0.56-0.99 with systematic
      differences (P < 0.05) between test and retest in 3 of the tasks. The sit-up task
      was excluded due to low intrarater reliability resulting in the final 7-item FI
      2. There was a good correlation between tasks on the right and left side
      suggesting that the FI-2 could be performed unilaterally. CONCLUSION: The FI-2 is
      a valid and reliable outcome measure of impairment for patients with polymyositis
      or dermatomyositis. It is well tolerated and the unilateral FI-2 requires a
      maximum of 20 minutes to perform. Further evaluation of sensitivity to change and
      testing in healthy individuals needs to be conducted.

PMID- 16463423
TI  - Lack of detection of human retrovirus-5 proviral DNA in synovial tissue and blood
      specimens from individuals with rheumatoid arthritis or osteoarthritis.
AB  - OBJECTIVE: Prior studies have suggested an association of human retrovirus 5 with
      rheumatoid arthritis. The purpose of this study was to determine if human
      retrovirus-5 proviral DNA is present in synovial tissue and blood specimens from
      patients with rheumatoid arthritis or osteoarthritis, or those without joint
      disease. METHODS: Synovial tissue and whole blood from 75 patients with
      rheumatoid arthritis, 75 patients with osteoarthritis, and 50 patients without a
      primary arthritis diagnosis were assayed by real-time quantitative polymerase
      chain reaction (PCR) using primers that amplify a 186-bp fragment of human
      retrovirus-5 proviral DNA. RESULTS: A total of 200 tissue specimens, 200
      mononuclear cells, and 196 of 200 granulocyte specimens tested negative for human
      retrovirus-5 proviral DNA. No association between human retrovirus 5 and
      rheumatoid arthritis or osteoarthritis (P = 0.516) was identified. Granulocyte
      specimens from 4 patients, 2 with rheumatoid arthritis and 2 with osteoarthritis,
      yielded a low positive human retrovirus-5 proviral DNA signal (83-1,365 copies of
      human retrovirus-5 proviral DNA/ml blood). CONCLUSION: Contrary to prior reports,
      we did not find an association between human retrovirus 5 and rheumatoid
      arthritis or osteoarthritis using a real-time PCR assay. Our findings are
      consistent with the recent finding that human retrovirus 5 is actually rabbit
      endogenous retrovirus H.

PMID- 16463424
TI  - Chronic periaortitis and HLA-DRB1*03: another clue to an autoimmune origin.
AB  - OBJECTIVE: Patients with chronic periaortitis (CP) often show clinical and
      laboratory findings of a systemic autoimmune disorder. The aim of the present
      study was to investigate the role of the HLA system in CP. METHODS: Low
      resolution genotyping for HLA-A, HLA-B, and HLA-DRB1 loci and genotyping of TNFA(
      238)A/G and TNFA(-308)A/G single nucleotide polymorphisms were performed in 35
      consecutive patients with CP and 350 healthy controls. RESULTS: The HLA-DRB1*03
      allele frequency was strikingly higher in patients with CP than in controls
      (24.28% versus 9.14%; chi(2) = 15.50, P = 0.000084, corrected P [P(corr)] =
      0.0012, odds ratio [OR] 3.187, 95% confidence interval [95% CI] 1.74-5.83); the
      HLA-B*08 allele frequency was also higher in patients than in controls (17.14%
      versus 6.28%; chi(2)=11.12, P = 0.0008, P(corr) = 0.0269, OR 3.085, 95% CI 1.54
      6.16). The A*01 allele frequency was significantly different (P = 0.0463), but
      the statistical significance was lost after correction for multiple testing
      (P(corr) = 0.5088). TNFA(-238)A allele and TNFA(-308)A allele frequencies were
      not significantly different (P = 0.512 and P = 0.445, respectively). Comparison
      of the main clinical and laboratory findings suggestive of a systemic autoimmune
      disease (e.g., acute-phase reactants, constitutional symptoms, other autoimmune
      diseases associated with CP) between the HLA-DRB1*03-positive and the HLA-DRB1*03
      negative patients showed that the former group had significantly higher levels of
      C-reactive protein (P = 0.045) at disease onset, although this difference was not
      statistically significant after correction for multiple tests (P(corr) = 0.369).
      CONCLUSION: The HLA system plays a role in susceptibility to CP. The strong
      association between CP and HLA-DRB1*03, an allele linked to a wide range of
      autoimmune conditions, further supports the view that CP may represent a clinical
      manifestation of an autoimmune disease.

PMID- 16463425
TI  - Repetitive 18F-fluorodeoxyglucose positron emission tomography in giant cell
      arteritis: a prospective study of 35 patients.
AB  - OBJECTIVE: To study fluorodeoxyglucose (FDG) uptake in the different vascular
      beds and in the large joints of patients with giant cell arteritis (GCA) at
      diagnosis, during steroid treatment, and at relapse. METHODS: All consecutive
      patients admitted to our department with a diagnosis of GCA underwent FDG
      positron emission tomography (PET) scan before treatment with methylprednisolone
      was started. PET scans were repeated at 3 and 6 months, if the initial PET scans
      showed vascular FDG uptake. PET scans were scored at 7 different vascular areas
      and a total vascular score (TVS) was calculated, ranging from 0 to 21. RESULTS: A
      total of 35 patients entered the study. At diagnosis, vascular FDG uptake was
      noted in 29 patients (83%), especially in the subclavian arteries (74%), but also
      in the aorta (>50%) and up to the femoral arteries (37%). TVS decreased from a
      mean +/- SD score of 7.9 +/- 5.5 at baseline to 2.4 +/- 3.5 on repeat PET scan at
      3 months (P < 0.0005), but did not further decrease at 6 months. The patients who
      relapsed had similar earlier decreases of TVS compared with those who did not
      relapse. FDG uptake in the shoulders at diagnosis correlated significantly with
      the presence of polymyalgia rheumatica (P = 0.005). CONCLUSION: FDG uptake in the
      large vessels is a sensitive marker for GCA, which can involve the larger
      thoracic, abdominal, and peripheral arteries. Polymyalgia rheumatica symptoms in
      patients with GCA correlate with (peri)synovitis of the shoulders. Relapses of
      GCA cannot be predicted by results of former PET scintigraphies.

PMID- 16463426
TI  - Scleroderma treatment differs between experts and general rheumatologists.

PMID- 16463427
TI  - Thromboembolic events as a complication of antineutrophil cytoplasmic antibody
      associated vasculitis.

PMID- 16463428
TI  - Effect of anti-tumor necrosis factor alpha therapy on the progression of
      subclinical atherosclerosis in severe rheumatoid arthritis.

PMID- 16463429
TI  - Pregnancy-related polymyositis and massive perivillous fibrin deposition in the
      placenta: are they pathogenetically related?

PMID- 16463430
TI  - Pulmonary fibrosis in a patient with rheumatoid arthritis treated with
      adalimumab.

PMID- 16463431
TI  - Splitting high-dose oral methotrexate improves bioavailability: a pharmacokinetic
      study in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To study the bioavailability of a divided higher oral dose of
      methotrexate (MTX), in comparison to a single dose, in adult patients with
      rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in
      10 patients with RA taking a stable dose (25-35 mg weekly) of MTX. Separated by
      one week, a pharmacokinetic analysis was performed in each patient after an oral
      single dose, and after an equal but split dose separated by 8 hours. MTX serum
      concentrations were measured by a fluorescence polarization immunoassay
      technique. Analysis was performed by calculation of the area under the curve
      (AUC) by the trapezoidal rule and by means of an iterative 2-stage Bayesian
      population procedure, obtaining population and individual pharmacokinetic
      parameters. For the population analysis, data from 15 patients in our previous
      study comparing oral and subcutaneous administration of MTX were also used.
      RESULTS: The median MTX dose was 30 mg weekly (range 25-35 mg). The
      bioavailability of the split dose was 28% higher compared to the single dose (p =
      0.007). In the population pharmacokinetic modeling, a 2-compartment model best
      described the serum MTX concentration versus time curves. The mean
      bioavailability after single-dose and split-dose MTX was 0.76 and 0.90,
      respectively, compared to subcutaneous administration. There was a statistically
      significant difference in the bioavailability of the 2 oral administration
      regimens (p = 0.008). CONCLUSION: The bioavailability of oral higher dose MTX in
      adult patients with RA can be improved by splitting the dose.

PMID- 16463432
TI  - Utilization and cost comparison of current and optimal prescribing of
      nonsteroidal antiinflammatory drugs in Quebec, Canada.
AB  - OBJECTIVE: Clinical practice guidelines recommend prophylactic use of
      gastroprotective agents (GPA) with nonselective nonsteroidal antiinflammatory
      drugs (nsNSAID) for patients at risk of gastrointestinal (GI) complications. We
      estimated the costs of cyclooxygenase-2 selective inhibitors, nsNSAID, and
      concurrent GPA prescribed in 2002 in Quebec, Canada, and compared these to
      estimated costs if prescribing followed guideline recommendations. METHODS: We
      used the Quebec government medical and pharmaceutical claims database (RAMQ). All
      prescriptions for NSAID and concurrent GPA dispensed between January 1 and
      December 31, 2002, were evaluated for continuously covered beneficiaries 18 years
      of age or older. Prescriptions were stratified by patient GI risk factors
      determined at the dispensing date of each prescription into low-, moderate-,
      elevated-, and high-risk categories. Five scenarios of "appropriate" NSAID
      therapy were identified using clinical practice guidelines. The potential effect
      on the prescription drug budget of implementing each of these scenarios was
      estimated. RESULTS: In total, 503,671 patients filled 1,863,171 prescriptions for
      NSAID, representing 41.1 million days of treatment with total expenditures of
      about dollar 94 million CDN for NSAID and concurrent GPA. Average actual daily
      costs for coxibs (rofecoxib and celecoxib), celecoxib, nsNSAID, and concurrent
      GPA were dollar 1.94, dollar 2.06, dollar 1.19, and dollar 2.30, respectively.
      Prescribing nsNSAID with GPA to all patients at moderate and elevated risks while
      prescribing NSAID without GPA to patients at low risk, and celecoxib with a GPA
      to patients at very high risk would have cost dollar 36.4 million more, mainly
      due to the additional cost of GPA. CONCLUSION: Compared to actual prescribing
      patterns, a prescribing strategy consistent with clinical practice guidelines can
      increase drug acquisition costs to the healthcare payer.

PMID- 16463433
TI  - Developing classification criteria for peripheral joint psoriatic arthritis. Step
      I. Establishing whether the rheumatologist's opinion on the diagnosis can be used
      as the "gold standard".
AB  - OBJECTIVE: The study of psoriatic arthritis (PsA) is hampered by the absence of a
      widely accepted, validated case definition. We investigated whether the
      physician's opinion can be used as a gold standard when developing classification
      criteria for peripheral joint PsA. METHODS: UK rheumatologists who had published
      on PsA and attendees at 3 international meetings on PsA held in the UK were
      polled by questionnaire. There were 3 phases. The first questionnaire asked
      whether rheumatologists believed in the construct of PsA. The second survey
      developed a list of features thought to distinguish patients with PsA from other
      forms of peripheral arthritis. The final phase was development of a series of 61
      "paper" patients with various combinations of the features of PsA. The paper
      patients were assessed by 15 rheumatologists who were asked whether, in their
      opinion, the patient had PsA. Latent class analysis was used to identify
      subgroups of patients and cross-tabulations were used to identify which clinical
      and laboratory features were associated with each subgroup. RESULTS:
      Rheumatologists agreed on the construct of PsA and that not all patients with
      psoriasis and an inflammatory polyarthritis have PsA. Latent class analysis
      identified 3 classes, corresponding to definite PsA; a middle group that was very
      likely to be given a diagnosis of PsA by some rheumatologists (high diagnosers),
      but unlikely to be given the diagnosis by others (low diagnosers); and a third
      group corresponding to "probably not PsA." CONCLUSION: For the group of patients
      with "definite PsA" the physician's opinion can be taken as the gold standard
      when developing classification criteria. However, for patients in the "middle
      group" there will always be disagreement with the gold standard whether the
      standard is based on the opinion of the high diagnosers or the low diagnosers.

PMID- 16463434
TI  - Increased concentration of proatherogenic inflammatory cytokines in systemic
      lupus erythematosus: relationship to cardiovascular risk factors.
AB  - OBJECTIVE: . To examine the hypothesis that patients with systemic lupus
      erythematosus (SLE) have increased concentrations of interleukin-6 (IL-6), IL-8,
      and monocyte chemoattractant protein-1 (MCP-1) and that these cytokines are
      associated with coronary risk factors and atherosclerosis. METHODS: Plasma IL-6,
      MCP-1, and serum IL-8 (pg/ml) concentrations were measured in 74 patients with
      SLE and in 85 controls. Clinical characteristics, homocysteine, lipids,
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and coronary
      artery calcification as detected by electron beam computed tomography were
      measured. RESULTS: IL-6 (13.2 +/- 13.8 pg/ml vs 6.7 +/- 3.2 pg/ml, p < 0.001) and
      MCP-1 (264.2 +/- 581.8 pg/ml vs 131.0 +/- 63.7 pg/ml, p < 0.001) concentrations
      were higher in patients with lupus than in controls. IL-8 concentrations did not
      differ between patients and controls (p = 0.86). In patients, IL-6 concentrations
      were correlated with CRP (p < 0.001), ESR (p < 0.001), SLE disease activity index
      (SLEDAI, p = 0.003), and body mass index (BMI, p = 0.003). IL-6 concentrations
      were inversely correlated with HDL cholesterol (p = 0.01). MCP-1 concentrations
      were correlated with SLEDAI (p = 0.01), ESR (p = 0.04), and triglycerides (p =
      0.03). After controlling for age, sex, disease activity, SLICC damage index,
      smoking status, and systolic blood pressure, IL-6 was associated with coronary
      calcification (odds ratio, OR = 1.07, p = 0.035). Similar models found no
      association between MCP-1 or IL-8 with coronary artery calcification. CONCLUSION:
      Patients with SLE have increased concentrations of IL-6 and MCP-1. These
      cytokines are associated with increased inflammation, BMI, and adverse lipid
      profiles. IL-6 is associated with burden of atherosclerosis in SLE.

PMID- 16463436
TI  - Desensitization to hydroxychloroquine--experience of 4 patients.
AB  - Hydroxychloroquine (HCQ) is an antimalarial agent with immunomodulatory effects.
      It is widely used in rheumatologic diseases, and has a very high
      efficacy/toxicity ratio. It is particularly important in the treatment of
      systemic lupus erythematosus (SLE) since it reduces new organ involvement and
      disease flares, and relieves skin and joint symptoms. Some patients develop
      hypersensitivity rash in response to HCQ. In such patients the drug is withdrawn
      and replaced by another medication. All the alternative medications for
      rheumatological patients are significantly more toxic than HCQ. We describe our
      initial experience of HCQ slow oral desensitization. All 4 patients who were
      recruited completed the procedure successfully without significant difficulty.
      Our results suggest that HCQ slow oral desensitization is safe, effective, and
      easy to perform.

PMID- 16463435
TI  - Continued inhibition of radiographic progression in patients with psoriatic
      arthritis following 2 years of treatment with etanercept.
AB  - OBJECTIVE: Clinical and radiographic responses were evaluated in patients with
      psoriatic arthritis (PsA) treated for up to 2 years with etanercept. METHODS:
      Patients were previously randomized to receive placebo or etanercept in a double
      blind study and chose to participate in the current open-label extension phase.
      All patients received etanercept 25 mg twice weekly. Radiographic progression was
      determined at baseline, 1 year, and 2 years using the Sharp method modified to
      include joints frequently affected in PsA. Arthritis and psoriasis responses were
      determined using American College of Rheumatology 20% (ACR20) improvement
      criteria, PsA response criteria (PsARC), and the psoriasis area severity index
      (PASI). RESULTS: Of 205 patients randomized, 169 entered open-label, and 141 [71
      randomized to receive placebo (placebo/etanercept) and 70 randomized to receive
      etanercept (etanercept/etanercept)] had radiographic data available for analysis
      at 2 years. ACR20 criteria, PsARC, and PASI 50 criteria were met by 64%, 84%, and
      62%, respectively, of etanercept/etanercept patients at the end of the 48-week
      open-label period. Placebo/etanercept patients achieved comparable results within
      12 weeks that were sustained at 48 weeks (63%, 80%, and 73%). Radiographic
      progression was inhibited in the etanercept/ etanercept patients (mean adjusted
      change in total Sharp score of -0.38 from baseline to 2 yrs). In
      placebo/etanercept patients, disease progression was inhibited once patients
      began receiving etanercept (mean adjusted change of -0.22 from 1 year to 2
      years). Adverse event rates were similar to those observed during randomized
      phase, with only one serious adverse event deemed possibly related to etanercept.
      CONCLUSION: These data demonstrate a sustained benefit of etanercept treatment,
      including inhibition of radiographic progression, in patients with PsA.

PMID- 16463437
TI  - Prospective observational analysis of the efficacy and safety of low-dose (3
      mg/kg) infliximab in ankylosing spondylitis: 4-year followup.
AB  - OBJECTIVE: Although there are now compelling data that infliximab is effective
      for the treatment of AS, most studies have evaluated a dose of 5 mg/kg rather
      than the 3 mg/kg dose recommended for patients with RA. We assessed the
      effectiveness and safety of a 3 mg/kg dose of infliximab in normal clinical
      practice over several years of followup. METHODS: All consecutive patients with
      AS starting infliximab therapy at 3 mg/kg IV at 0, 2, and 6 weeks and q 2 months
      between April 2000 and December 2004 were included. Data were systematically
      collected at baseline, at 14 weeks, and every 6 months thereafter to 4 years or
      withdrawal. Data included demographic characteristics, Bath AS indices, adverse
      events, and reasons for withdrawal. Survival taking low-dose infliximab was
      analyzed by the Kaplan-Meier method with withdrawal for lack of efficacy and/or
      adverse events and requirement for dose escalation constituting the endpoint.
      RESULTS: Thirty-four patients (M:F = 26:8), mean age 44.9 years, mean disease
      duration 17.1 years, and mean BASDAI of 6.4, were studied, of whom 17 had active
      peripheral synovitis. Median duration of treatment with low-dose infliximab was
      1507 days. Fourteen discontinued therapy after a median of 91 days, 6 for adverse
      events, 6 for lack of efficacy, and 2 were lost to followup. Five (14.7%)
      patients required dose escalation. Effectiveness demonstrable at 1 year was
      maintained over 4 years. We did not identify any significant baseline predictors
      of maintenance on low dose infliximab for > or = 2 years. CONCLUSION: Low-dose (3
      mg/kg) infliximab therapy is associated with sustained effectiveness in patients
      with AS in the real-world setting.

PMID- 16463438
TI  - Impairment of IGF-I gene splicing and MGF expression associated with muscle
      wasting.
AB  - The characterisation of a local tissue repair factor (mechano growth factor, MGF)
      that is produced by exercised and/or damaged muscle by differential splicing of
      the IGF-I gene provides understanding of how muscle is maintained in the young
      normal individual. Mechano growth factor, or MGF, is different to the systemic
      IGF-I as it has an insert of 49 base pairs in exon 5 that introduces a reading
      frame shift resulting in a C terminal peptide with unique properties. Muscle is a
      post-mitotic tissue and as cell replacement is not a means of tissue repair there
      has to be an efficient local repair mechanism otherwise the damaged cells undergo
      cell death. The extra nuclei for muscle repair and hypertrophy are provided by
      the muscle satellite (stem) cells. The pool of these stem cells is apparently
      replenished by the action of MGF, which is produced as a pulse following a
      mechanical challenge. Unfortunately, the production of MGF is deficient in
      certain diseases such as in the muscular dystrophies in which the
      mechanotransduction mechanism, which may involve the dystrophin complex, is
      defective. In elderly muscles, decreased levels of growth hormone apparently mean
      that there is less primary RNA transcript of the IGF-I gene to be spliced towards
      MGF. Consequently, there is an increasing inability to maintain muscle mass
      during ageing. Delivery of MGF and cDNA or peptide produces marked increases in
      the strength of normal as well as diseased muscle and, therefore, MGF has
      considerable potential as a generic means of treating muscle cachexia.

PMID- 16463440
TI  - Japan promises to curb number of suicides.

PMID- 16463439
TI  - Erratum to "The change in length of the medial and lateral collateral ligaments
      during in vivo knee flexion".
AB  - The collateral ligaments of the knee are important in maintaining knee stability.
      However, little data has been reported on the in vivo function of the collateral
      ligaments. The objective of this study was to investigate the change in length of
      different fiber bundles of the medial collateral ligament (MCL), deep fibers of
      the MCL (DMCL) and the lateral collateral ligament (LCL) during in vivo knee
      flexion. The knees of five healthy subjects were scanned using magnetic resonance
      imaging. These images were used to create three-dimensional models of the tibia
      and femur, including the insertions of the collateral ligaments. The MCL, DMCL,
      and LCL were each divided into three equal portions: an anterior bundle, a middle
      bundle and a posterior bundle. Next, the subjects were imaged from two orthogonal
      directions using fluoroscopy while performing a quasi-static lunge from 0 degrees
      to 90 degrees of flexion. The models and fluoroscopic images were then used to
      reproduce the in vivo motion of the knee. From these models, the length of each
      bundle of each ligament was measured as a function of flexion. The length of the
      anterior bundle of the MCL did not change significantly with flexion. The length
      of the posterior bundle of the MCL consistently decreased with flexion (p <
      0.05). The change in length of the DMCL with flexion was similar to the trend
      observed for the MCL. The length of the anterior bundle of the LCL increased with
      flexion and the length of the posterior bundle decreased with flexion. These data
      indicate that the collateral ligaments do not elongate uniformly as the knee is
      flexed, with different bundles becoming taut and slack. These data may help to
      provide a better understanding of the in vivo function of the collateral
      ligaments and be used to improve surgical reconstructions of the collateral
      ligaments. Furthermore, the data suggest that the different roles of various
      portions of the collateral ligaments along the flexion path should be considered
      before releasing the collateral ligaments during knee arthroplasty.

PMID- 16463441
TI  - Military incursions into aid work anger humanitarian groups.

PMID- 16463442
TI  - Going global.

PMID- 16463443
TI  - School's in for summer.

PMID- 16463444
TI  - Nanoscience factory.

PMID- 16463445
TI  - Medicine in pregnancy. Part 1. Lifestyle issues and minor complaints.

PMID- 16463446
TI  - IO you one.

PMID- 16463447
TI  - IO you one.

PMID- 16463448
TI  - IO you one.

PMID- 16463449
TI  - Acute abdominal eviscerations.

PMID- 16463450
TI  - Interagency Council on Information Resources for Nursing.

PMID- 16463451
TI  - Revised medical criteria for evaluating cardiovascular impairments. Final rules.
AB  - We are revising the criteria in the Listing of Impairments (the listings) that we
      use to evaluate claims involving cardiovascular impairments. We apply these
      criteria when you claim benefits based on disability under title II and title XVI
      of the Social Security Act (the Act). The revisions reflect advances in medical
      knowledge, treatment, and methods of evaluating cardiovascular impairments.

PMID- 16463452
TI  - 'Woman bites dog' article on domestic violence: author's reply to Dr Goodyear
      Smith's letter.

PMID- 16463453
TI  - Using medication reconciliation to prevent errors.

PMID- 16463454
TI  - [Computer terminal in the physician's office to assist drug prescription].

PMID- 16463455
TI  - Torts, expertise, and authority: liability of physicians and managed care
      organizations.
AB  - We examine optimal individual and entity-level liability for negligence when
      expected accident costs depend on both the agent's level of expertise and the
      principal's level of authority. We consider these issues in the context of
      physician and managed care organization (MCO) liability for medical malpractice.
      Under current law, physicians generally are considered independent contractors
      and hence MCOs are not liable for negligent acts by physicians. We find that the
      practice of reviewing the medical decisions of physicians affects their
      incentives to take care, which in turn implies that it is efficient for MCOs to
      be held liable for the torts committed by their physicians.

PMID- 16463456
TI  - S-nitrosoglutathione added to the University of Wisconsin solution prevents
      morphological alteration on rat livers.

PMID- 16463457
TI  - Polarographic measurement of oxygen content in cold storage solutions for
      isolated cells.

PMID- 16463458
TI  - The urea cycle enzymes activity and its gene expression in rat hepatocytes are
      not affected by cold storage in University of Wisconsin solution.

PMID- 16463459
TI  - The heme oxygenase system and organ preservation: studies towards protection in a
      kidney model.

PMID- 16463460
TI  - What is the meaning of cellular viability.

PMID- 16463461
TI  - [Fundamental studies on sleep-arousal regulation].

PMID- 16463462
TI  - [Tasks and expectations for drug design based on pharmacogenomics].

PMID- 16463463
TI  - [Suddenly, the last summer].

PMID- 16463464
TI  - Death obsession in Palestinians.
AB  - The authors explored death obsession level and correlates among a sample (N =
      601) of Palestinians living in the city of Beit Jala, the village of Al-Khader,
      and the Aida refugee camp in the Bethlehem area. They live in war conditions; the
      houses of half of them have been demolished. The Death Obsession Scale (DOS) was
      administered. Its alpha reliability was .92, denoting high internal consistency.
      Among women, it yielded 1 factor, (General Death Obsession), whereas among men it
      yielded 3 factors: Death Rumination, Death Dominance, and Death Idea Repetition.
      Palestinian men and women attained significantly lower DOS mean scores than
      participants from 4 Arab countries: Egypt, Kuwait, Syria, and Lebanon in 7 out of
      8 comparisons. However, Palestinian women had significantly higher DOS mean score
      than their Spanish, American and British counterparts, whereas Palestinian men
      had significantly higher mean DOS score than Spanish peers. The low DOS scores of
      Palestinians, in proportion to other Arab samples, may reflect their adaptation
      to strife and violence.

PMID- 16463465
TI  - Content analysis of free-response narratives to personal meanings of death among
      Chinese children and adolescents.
AB  - The study explores development of the concept of death among 204 Chinese children
      and adolescents and analyzes the relationships between death concept development
      and background variables. A coding manual for content analysis of death
      constructs adapted from R. A. Neimeyer et al. (1983) was used to classify each
      construct in the paragraphs written by participants regarding their views of
      death. The 6 categories most frequently identified were Internal Causality,
      Negative Emotion State, External Causality, Nonexistence, Negative Body State,
      and Existence. Death-related experiences did not significantly influence concepts
      regarding death, while significant differences emerged as a function of grade,
      gender, religion, and family death discussion for several death constructs.
      Compared with earlier American samples, Chinese children and adolescents
      identified less with choice and purposeful death constructs and were less likely
      to view death in terms of personal choice and morals or in terms of psychological
      or natural meaning. Whether the differences were due to cultural, methodological
      or age factors deserves further study. Finally, this study concludes with some
      recommendations for the future study of death constructs.

PMID- 16463466
TI  - Sense of belonging as a predictor of reasons for living in older adults.
AB  - In response to the high rate of suicide among aging people, this study
      investigated sense of belonging as a predictor of reasons for living in an aged
      sample. A community sample of 104 Australians aged 61 to 95 years completed The
      Reasons for Living Inventory and The Sense of Belonging Instrument. Results
      indicated that a higher sense of belonging predicted more reasons to live
      overall, and child-related concerns, responsibility to family, and survival and
      coping beliefs, specifically. Future research should investigate if the
      enhancement of a sense of belonging among older adults is associated with an
      increase in reasons for living.

PMID- 16463469
TI  - Enrollment nightmare forces states to enact emergency drug coverage.

PMID- 16463468
TI  - Recognition of suicide risk according to the characteristics of the suicide
      process.
AB  - The suicide of a patient is a painful experience for many physicians and mental
      health professionals, and may contribute to the earlier and more frequent
      development of professional burnout. To reduce this risk in the primary care
      settings in which many suicidal patients are seen prior to their attempt, the
      authors presented concepts regarding the course of suicidal ideation and typical
      ways in which suicidal individuals communicate their experiences. These issues
      are explored through theoretical viewpoints, available records, research on
      suicide notes, and a review of the literature. The research findings presented
      can contribute to suicide prevention particularly when the risk of death is
      severe.

PMID- 16463467
TI  - Characteristics of Chinese suicide attempters: an emergency room study.
AB  - Studying the characteristics of attempted suicide is helpful in knowing the
      background of some completed suicides and improving prevention or intervention
      strategies. This current study analyzed data of 74 suicide attempters and 92
      accident injured patients admitted to 6 hospital emergency rooms in an area of
      Northeastern China and found both similarities and differences between Chinese
      and Western suicide attempters. The data show that more women than men attempted
      suicide. Perhaps because of the unavailability of firearms to Chinese civilians,
      pesticide was the most lethal means of suicidal behavior. The stressful life
      events that account for the majority of suicidal incidents were mostly familial
      or marital problems. Compared with accident victims, these Chinese suicide
      attempters were younger, poorer, more likely to believe in a
      religion/superstition, more likely to perceive gender inequality, and less likely
      to experience support from either family or community. The traditional culture
      downplaying the status of women coupled with a belief in the transmigration of
      life may play an important role in the suicide of Chinese young women.

PMID- 16463470
TI  - Payment fluctuations don't stop physicians from accepting Medicare patients.

PMID- 16463471
TI  - IPF payment changes could buy better psychiatric care.

PMID- 16463472
TI  - A space to dream.

PMID- 16463473
TI  - A visual analytics agenda.

PMID- 16463474
TI  - 3D modeling with the Tinmith mobile outdoor augmented reality system.

PMID- 16463475
TI  - A 3D visualization system for hurricane storm-surge flooding.

PMID- 16463476
TI  - BRDF-shop: creating physically correct bidirectional reflectance distribution
      functions.

PMID- 16463477
TI  - Secrets to success and fatal flaws: the design of large-display groupware.

PMID- 16463478
TI  - Visualization of structured nonuniform grids.

PMID- 16463479
TI  - Applying the peephole metaphor in a mixed-reality room.

PMID- 16463480
TI  - Hierarchical spherical distance fields for collision detection.

PMID- 16463482
TI  - Believing is seeing: cultivating radical media innovations.

PMID- 16463481
TI  - An introductory tour of interactive rendering.

PMID- 16463483
TI  - Linear and nonlinear equivalent circuit modeling of CMUTs.
AB  - Using piston radiator and plate capacitance theory capacitive micromachined
      ultrasound transducers (CMUT) membrane cells can be described by one-dimensional
      (1-D) model parameters. This paper describes in detail a new method, which
      derives a 1-D model for CMUT arrays from finite-element methods (FEM)
      simulations. A few static and harmonic FEM analyses of a single CMUT membrane
      cell are sufficient to derive the mechanical and electrical parameters of an
      equivalent piston as the moving part of the cell area. For an array of parallel
      driven cells, the acoustic parameters are derived as a complex mechanical fluid
      impedance, depending on the membrane shape form. As a main advantage, the
      nonlinear behavior of the CMUT can be investigated much easier and faster
      compared to FEM simulations, e.g., for a design of the maximum applicable voltage
      depending on the input signal. The 1-D parameter model allows an easy description
      of the CMUT behavior in air and fluids and simplifies the investigation of wave
      propagation within the connecting fluid represented by FEM or transmission line
      matrix (TLM) models.

PMID- 16463484
TI  - CMUT array modeling through free acoustic CMUT modes and analysis of the fluid
      CMUT interface through Fourier transform methods.
AB  - A method for analyzing capacitive micromachined ultrasonic transducer (CMUT)
      arrays and arrays of elements composed of several CMUTs is proposed. It is based
      on a combination of a free acoustic mode description of an isolated CMUT, and the
      coupling of these modes to the fluid in which waves should be excited or detected
      through an impedance matrix that will depend on frequency. The parameters of the
      model describing the isolated CMUT is independent of frequency and excitation of
      neighbor CMUTs, whereas the acoustic impedance matrix describing the coupling to
      the fluid will depend on both the excitation of neighbor CMUTs and frequency.
      Hence, this splitting of the calculations has a potential for saving computer
      time. The analysis gives transfer functions from excitations that vary
      harmonically with time and space along the array surface to CMUT parameters as
      current, mode excitations, or output acoustic pressure. Based on this, the
      response of essentially arbitrary excitations of the CMUTs may be obtained. The
      method is used to analyze an infinitely large array of circular CMUTs on a
      rectangular grid. The CMUTs are assumed to be operating in collapsed mode. Sharp
      resonances are shown to occur that could be significantly damped by adding series
      resistors to the CMUTs or increasing the water viscosity.

PMID- 16463485
TI  - Finite-element analysis of capacitive micromachined ultrasonic transducers.
AB  - In this paper, we present the results of finite-element analysis performed to
      investigate capacitive micromachined ultrasonic transducers (CMUTs). Both three
      dimensional (3-D) and 2-D models were developed using a commercially available
      finite-element modeling (FEM) software. Depending on the dimensionality of the
      model, the membranes were constructed using plane or shell elements. The
      electrostatic gap was modeled using many parallel plate transducers. An
      axisymmetric model for a single membrane was built; the electrical input
      impedance of the device then was calculated in vacuum to investigate series and
      parallel resonant frequencies, where the input impedance has a minimum and a
      maximum, respectively. A method for decomposing the membrane capacitance into
      parasitic and active parts was demonstrated, and it was shown that the parallel
      resonant frequency shifted down with increased biased voltage. Calculations then
      were performed for immersion transducers. Acoustic wave propagation was simulated
      in the immersion medium, using appropriate elements in a 3-D model. Absorbing
      boundaries were implemented to avoid the reflections at the end of the medium
      mesh. One row of an array element, modeled with appropriate boundary conditions,
      was used to calculate the output pressure. The results were compared with a
      simpler model: a single membrane in immersion, with symmetry boundary conditions
      on the sidewalls that cause the calculations to reflect the properties of an
      infinitely large array. A 2-D model then was developed to demonstrate the effect
      of membrane dimensions on the output pressure and bandwidth. Our calculations
      revealed that the small signal transmit pressure was inversely proportional to
      the square root of gap height. We also compared FEM results with analytical and
      experimental results.

PMID- 16463486
TI  - A finite difference model for cMUT devices.
AB  - A finite difference method was implemented to simulate capacitive micromachined
      ultrasonic transducers (cMUTs) and compared to models described in the literature
      such as finite element methods. Similar results were obtained. It was found that
      one master curve described the clamped capacitance. We introduced normalized
      capacitance versus normalized bias voltage and metallization rate, independent of
      layer thickness, gap height, and size membrane, leading to the determination of a
      coupling factor master curve. We present here calculations and measurements of
      electrical impedance for cMUTs. An electromechanical equivalent circuit was used
      to perform simulations. Our experimental measurements confirmed the theoretical
      results in terms of resonance, anti-resonance frequencies, clamped capacitance,
      and electromechanical coupling factor. Due to inhomogeneity of the tested element
      array and strong parasitic capacitance between cells, the maximum coupling
      coefficient value achieved was 0.27. Good agreement with theory was obtained for
      all findings.

PMID- 16463487
TI  - Optimization of the gain-bandwidth product of capacitive micromachined ultrasonic
      transducers.
AB  - Capacitive micromachined ultrasonic transducers (cMUT) have large bandwidths, but
      they typically have low conversion efficiencies. This paper defines a performance
      measure in the form of a gain-bandwidth product and investigates the conditions
      in which this performance measure is maximized. A Mason model corrected with
      finite-element simulations is used for the purpose of optimizing parameters.
      There are different performance measures for transducers operating in transmit,
      receive, or pulse-echo modes. Basic parameters of the transducer are optimized
      for those operating modes. Optimized values for a cMUT with silicon nitride
      membrane and immersed in water are given. The effect of including an electrical
      matching network is considered. In particular, the effect of a shunt inductor in
      the gain-bandwidth product is investigated. Design tools are introduced, which
      are used to determine optimal dimensions of cMUTs with the specified frequency or
      gain response.

PMID- 16463488
TI  - Acoustic coupling in capacitive microfabricated ultrasonic transducers: modeling
      and experiments.
AB  - In the design of low-frequency transducer arrays for active sonar systems, the
      acoustic interactions that occur between the transducer elements have received
      much attention. Because of these interactions, the acoustic loading on each
      transducer depends on its position in the array, and the radiated acoustic power
      may vary considerably from one element to another. Capacitive microfabricated
      ultrasonic transducers (CMUT) are made of a two-dimensional array of metallized
      micromembranes, all electrically connected in parallel, and driven into flexural
      motion by the electrostatic force produced by an applied voltage. The mechanical
      impedance of these membranes is typically much lower than the acoustic impedance
      of water. In our investigations of acoustic coupling in CMUTs, interaction
      effects between the membranes in immersion were observed, similar to those
      reported in sonar arrays. Because CMUTs have many promising applications in the
      field of medical ultrasound imaging, understanding of cross-coupling mechanisms
      and acoustic interaction effects is especially important for reducing cross-talk
      between array elements, which can produce artifacts and degrade image quality. In
      this paper, we report a finite-element study of acoustic interactions in CMUTs
      and experimental results obtained by laser interferometry measurements. The good
      agreement found between finite element modeling (FEM) results and optical
      displacement measurements demonstrates that acoustic interactions through the
      liquid represent a major source of cross coupling in CMUTs.

PMID- 16463489
TI  - Design of a front-end integrated circuit for 3D acoustic imaging using 2D CMUT
      arrays.
AB  - Integration of front-end electronics with 2D capacitive micromachined ultrasonic
      transducer (CMUT) arrays has been a challenging issue due to the small element
      size and large channel count. We present design and verification of a front-end
      drive-readout integrated circuit for 3D ultrasonic imaging using 2D CMUT arrays.
      The circuit cell dedicated to a single CMUT array element consists of a high
      voltage pulser and a low-noise readout amplifier. To analyze the circuit cell
      together with the CMUT element, we developed an electrical CMUT model with
      parameters derived through finite element analysis, and performed both the pre-
      and postlayout verification. An experimental chip consisting of 4 X 4 array of
      the designed circuit cells, each cell occupying a 200 X 200 microm2 area, was
      formed for the initial test studies and scheduled for fabrication in 0.8 microm,
      50 V CMOS technology. The designed circuit is suitable for integration with CMUT
      arrays through flip-chip bonding and the CMUT-on-CMOS process.

PMID- 16463490
TI  - Capacitive micromachined ultrasonic transducers: fabrication technology.
AB  - Capacitive micromachined ultrasonic transducer (cMUT) technology is a prime
      candidate for next generation imaging systems. Medical and underwater imaging and
      the nondestructive evaluation (NDE) societies have expressed growing interest in
      cMUTs over the years. Capacitive micromachined ultrasonic transducer technology
      is expected to make a strong impact on imaging technologies, especially
      volumetric imaging, and to appear in commercial products in the near future. This
      paper focuses on fabrication technologies for cMUTs and reviews and compares
      variations in the production processes. We have developed two main approaches to
      the fabrication of cMUTs: the sacrificial release process and the recently
      introduced wafer-bonding method. This paper gives a thorough review of the
      sacrificial release processes, and it describes the new wafer-bonding method in
      detail. Process variations are compared qualitatively and quantitatively whenever
      possible. Through these comparisons, it was concluded that wafer-bonded cMUT
      technology was superior in terms of process control, yield, and uniformity.
      Because the number of steps and consequent process time were reduced (from six
      mask process to four-mask process), turn-around time was improved significantly.

PMID- 16463491
TI  - Design, fabrication and characterization of a capacitive micromachined ultrasonic
      probe for medical imaging.
AB  - In this paper we report the design, fabrication process, and characterization of
      a 64-elements capacitive micromachined ultrasonic transducer (cMUT), 3 MHz center
      frequency, 100% fractional bandwidth. Using this transducer, we developed a
      linear probe for application in medical echographic imaging. The probe was fully
      characterized and tested with a commercial echographic scanner to obtain first
      images from phantoms and in vivo human body. The results, which quickly follow
      similar results obtained by other researchers, clearly show the great
      potentiality of this new emerging technology. The cMUT probe works better than
      the standard piezoelectric probe as far as the axial resolution is concerned, but
      it suffers from low sensitivity. At present this can be a limit, especially for
      in depth operation. But we are strongly confident that significant improvements
      can be obtained in the very near future to overcome this limitation, with a
      better transducer design, the use of an acoustic lens, and using well matched,
      front-end electronics between the transducer and the echographic system.

PMID- 16463492
TI  - Dynamic analysis of capacitive micromachined ultrasonic transducers.
AB  - Electrostatic transducers are usually operated under a DC bias below their
      collapse voltage. The same scheme has been adopted for capacitive micromachined
      ultrasonic transducers (cMUTs). DC bias deflects the cMUT membranes toward the
      substrate, so that their centers are free to move during both receive and
      transmit operations. In this paper, we present time-domain, finite element
      calculations for cMUTs using LS-DYNA, a commercially available finite element
      package. In addition to this DC bias mode, other new cMUT operations (collapse
      and collapse-snapback) have recently been demonstrated. Because cMUT membranes
      make contact with the substrate in these new operations, modeling of these cMUTs
      should include contact analysis. Our model was a cMUT transducer consisting of
      many hexagonal membranes; because it was symmetrical, we modeled only one-sixth
      of a hexagonal cell loaded with a fluid medium. The finite element results for
      both conventional and collapse modes were compared to measurements made by an
      optical interferometer; a good match was observed. Thus, the model is useful for
      designing cMUTs that operate in regimes where membranes make contact with the
      substrate.

PMID- 16463493
TI  - Piezoelectric micromachined ultrasonic transducers based on PZT thin films.
AB  - This paper describes fabrication and characterization results of piezoelectric
      micromachined ultrasonic transducers (pMUTs) based on 2-microm-thick
      Pb(Zr0.53Ti0.47O3) (PZT) thin films. The applied structures are circular plates
      held at four bridges, thus partially unclamped. A simple analytical model for the
      fully clamped structure is used as a reference to optimize design parameters such
      as thickness relations and electrodes, and to provide approximate predictions for
      coupling coefficients related to previously determined thin film properties. The
      best coupling coefficient was achieved with a 270-microm plate and amounted to
      kappa2 = 5.3%. This value compares well with the calculated value based on
      measured small signal dielectric (epsilon = 1050) and piezoelectric (e3l,f = 15
      Cm(-2)) properties of the PZT thin film at 100 kV/cm dc bias. The resonances show
      relatively large Q-factors, which can be partially explained by the small
      diameters as compared to the sound wavelength in air and in the test liquid
      (Fluorinert 77). A transmit-receive experiment with two quasi-identical pMUTs was
      performed showing significant signal transmission up to a distance of 20 cm in
      air and 2 cm in the test liquid.

PMID- 16463494
TI  - Fabrication and characterization of piezoelectric micromachined ultrasonic
      transducers with thick composite PZT films.
AB  - Ferroelectric microelectromechanical systems (MEMS) has been a growing area of
      research in past decades, in which ferroelectric films are combined with silicon
      technology for a variety of applications, such as piezo-electric micromachined
      ultrasonic transducers (pMUTs), which represent a new approach to ultrasound
      detection and generation. For ultrasound-radiating applications, thicker PZT
      films are preferred because generative force and response speed of the diaphragm
      type transducers increase with increasing film thickness. However, integration of
      4- to 20-microm thick PZT films on silicon wafer, either the deposition or the
      patterning, is still a bottleneck in the micromachining process. This paper
      reports on a diaphragm-type pMUT. A composite coating technique based on chemical
      solution deposition and high-energy ball milled powder has been used to fabricate
      thick PZT films. Micromachining of the pMUTs using such thick films has been
      investigated. The fabricated pMUT with crack-free PZT films up to 7-microm thick
      was evaluated as an ultrasonic transmitter. The generated sound pressure level of
      up to 120 dB indicates that the fabricated pMUT has very good ultrasound
      radiating performance and, therefore, can be used to compose pMUT arrays for
      generating ultrasound beam with high directivity in numerous applications. The
      pMUT arrays also have been demonstrated.

PMID- 16463495
TI  - Characterization of micromachined ultrasonic transducers using light diffraction
      tomography.
AB  - This paper demonstrates that light diffraction tomography can be used to measure
      the acoustic field of micromachined ultrasonic transducers (MUT) in cases in
      which standard methods like hydrophone and microphone measurements fail. Two
      types of MUTs have been characterized with the method, one air-coupled capacitive
      MUT (cMUT) and one waterloaded continuous wave (CW) miniature multilayer lead
      zirconate titanate (PZT) transducer. Light diffraction tomography is an
      ultrasound measurement method with some special characteristics. Based on the
      interaction of light and ultrasound, it combines light intensity measurements
      with tomography algorithms to produce a measurement system. The method offers
      nonperturbing pressure measurements with high spatial resolution. It has been
      shown that, under certain circumstances, light diffraction tomography can be used
      as an absolute pressure measurement method with accuracy in the order of 10% in
      water and 13% in air. The results show that air-coupled cMUTs in the frequency
      range of about 1 MHz as well as the extreme near field of a miniaturized CW 10
      MHz water-loaded transducer were successfully characterized with light
      diffraction tomography.

PMID- 16463496
TI  - Effects of nonlinear elastic constants on electromechanical coupling factors.
AB  - We studied the electromechanical coupling factor of an electroelastic plate from
      the nonlinear theory for large deformations and strong fields, in particular the
      effects of nonlinear elastic constants on the factor. The case of nonlinear
      thickness-shear deformation of an AT-cut quartz plate is calculated as an
      example.

PMID- 16463497
TI  - Mass sensitivity of antiplane (SH) modes in an isotropic elastic wedge.
AB  - A simple expression is obtained for the mass sensitivity of face-shear and
      thickness-twist modes in an isotropic elastic wedge with thin surface mass
      layers. The results suggest the possibility of wedge mode mass sensors.

PMID- 16463498
TI  - The effects of ZnO films on surface acoustic wave properties of modified lead
      titanate ceramic substrates.
AB  - Poly-crystal zinc oxide (ZnO) films with c-axis (002) orientation have been
      successfully grown on the strontium (Sr) modified lead titanate ceramic
      substrates with different Sr dopants by r.f. magnetron sputtering technique.
      Highly oriented ZnO films with c-axis normal to the substrates can be obtained
      under a total pressure of 10 mTorr containing 50% argon and 50% oxygen and r.f.
      power of 70 W for 3 hours. Crystalline structures of the films were investigated
      by X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force
      microscopy (AFM). The phase velocity, electromechanical coupling coefficient and
      temperature coefficient of frequency of surface acoustic wave (SAW) devices with
      ZnO/IDT/PT (IDT, inter-digital transducer; PT, PbTiO3 ceramics) structure were
      investigated. The devices with ZnO/IDT/PT structure shows that the ZnO film
      effectively raise the electromechanical coupling coefficient (kappa2) from 3.8%
      to 9.9% of the device with the concentrations of Sr dopants of 0.15. It also
      improves the temperature coefficient of frequency of SAW devices.

PMID- 16463499
TI  - Power dependence of distributed cavity phase-induced frequency biases in atomic
      fountain frequency standards.
AB  - We discuss the implications of using high-power microwave tests in a fountain
      frequency standard to measure the frequency bias resulting from distributed
      cavity-phase shifts. We develop a theory which shows that the frequency bias from
      distributed cavity phase depends on the amplitude of the microwave field within
      the cavity. The dependence leads to the conclusion that the frequency bias
      associated with the distributed cavity phase is typically both misestimated and
      counted twice within the error budget of fountain frequency standards.

PMID- 16463500
TI  - Phase noise in capacitively coupled micromechanical oscillators.
AB  - Phase noise in capacitively coupled microresonator-based oscillators is
      investigated. A detailed analysis of noise mixing mechanisms in the resonator is
      presented, and the capacitive transduction is shown to be the dominant mechanism
      for low-frequency 1/f-noise mixing into the carrier sidebands. Thus, the
      capacitively coupled micromechanical resonators are expected to be more prone to
      the 1/f-noise aliasing than piezoelectrically coupled resonators. The analytical
      work is complemented with simulations, and a highly efficient and accurate
      simulation method for a quantitative noise analysis in closed-loop oscillator
      applications is presented. Measured phase noise for a microresonator-based
      oscillator is found to agree with the developed analytical and simulated noise
      models.

PMID- 16463501
TI  - Investigating the significance of multiple scattering in ultrasound contrast
      agent particle populations.
AB  - The majority of the existing models describing the behavior of microbubble
      ultrasound contrast agents consider single, isolated microbubbles suspended in
      infinite media. The behavior of a microbubble population is predicted by summing
      the results for single microbubbles and ignoring multiple scattering effects. The
      aim of this investigation is to determine the significance of multiple scattering
      in microbubble populations and establish whether an alternative approach is
      required. In the first part of the work, linear models are derived to identify
      approximately the conditions under which multiple scattering may be expected. A
      nonlinear model for sound propagation in a microbubble suspension then is
      developed and used to examine multiple scattering at higher insonation pressures.
      Broadband attenuation measurements are described for two different types of
      microbubble suspension (albumin encapsulated octofluropropane and copolymer
      encapsulated isobutane) to ascertain whether or not multiple scattering may be
      observed experimentally. The results from the simulation work indicate that
      multiple scattering effects would be discernible at moderate concentrations
      (10(6) microbubbles/ml) such as may be present in vivo. The effect upon
      attenuation in the suspension would be pronounced, however, only if the
      population contained a sufficient proportion of relatively large (> 4 microm
      radius) microbubbles excited at their resonance frequency. This also is found to
      be the case experimentally. These findings may have important implications for
      the characterization of ultrasound contrast agents and their use in quantitative
      diagnostic techniques.

PMID- 16463502
TI  - Ultrasound attenuation measurement in the presence of scatterer variation for
      reduction of shadowing and enhancement.
AB  - Pulse-echo ultrasound display relies on many assumptions that are known to be
      incorrect. Departure from these makes interpretation of conventional ultrasound
      images difficult, and three-dimensional (3-D) visualizations harder still. For
      instance, shadowing and enhancement are the result of an incorrect assumption
      that sound attenuation is a function only of depth. Attempts to reduce such
      artefacts by estimating attenuation locally have been frustrated by large
      statistical variations and the influence of scatterer type. We address the latter
      by examining the influence of scatterer type on two existing attenuation
      estimation algorithms. This analysis is novel for one of the algorithms, and
      contains a correction to previously published work for the other. We then propose
      a novel algorithm that is less sensitive to scatterer variation. We also present
      a novel technique for handling large statistical variations based on combined
      assumptions of monotonicity and smoothness. We then assess the performance of
      each algorithm for correcting shadowing and enhancement in in vitro data, using a
      real time 3-D radio frequency (RF) ultrasound acquisition system developed for
      this purpose. The results show visible differences in attenuation estimates from
      each technique, which are supported by the theoretical analysis. The novel
      attenuation estimation algorithm does show less sensitivity to scatterer
      variation, though it results in a more noisy estimate. Nevertheless, the novel
      technique for reducing statistical variations is sufficient to allow some degree
      of correction of shadowing and enhancement in each case.

PMID- 16463503
TI  - Influence of material parameters on acoustic wave propagation modes in ZnO/Si bi
      layered structures.
AB  - The influences of material properties on acoustic wave propagation modes in
      ZnO/Si bi-layered structures are studied. The transfer matrix method is used to
      calculate dispersion relations, wave field distributions, and electromechanical
      coupling coefficients of acoustic wave propagation modes in ZnO/Si bi-layered
      systems, in which the thickness of the substrate is of the same order of
      magnitude as the wavelength of the propagating wave modes. The influences of the
      thin film parameters on the acoustic wave propagation modes and their
      electromechanical coupling coefficients of the wave modes also are obtained. In
      addition, some experimental results for characterizing the wave propagation modes
      and their frequencies have also been obtained, which agree well with the
      theoretical predictions.

PMID- 16463504
TI  - The excitation and detection of lamb waves with planar coil electromagnetic
      acoustic transducers.
AB  - Planar coil electromagnetic acoustic transducers (EMATs) are investigated for the
      excitation and detection of Lamb waves in nonferromagnetic metallic wave-guides.
      Such EMATs are attractive for certain applications due to their omni-directional
      sensitivity to wave modes with predominantly in-plane surface displacement, such
      as the So Lamb wave mode. A model is developed that enables the modal content of
      the radiated Lamb wave field from a transmitting EMAT to be calculated, and the
      output voltage from a receiving EMAT to be predicted when a Lamb wave mode is
      incident on it. The predictions from this model are compared with experimental
      data obtained from 12 different EMATs tested on a 5-mm thick aluminum plate, and
      good agreement is obtained. The model then is used to analyze the different
      effects that contribute to the overall Lamb wave modal sensitivity of an EMAT.
      The relationship between coil geometry and wavelength is examined.

PMID- 16463505
TI  - Air-coupled through-transmission fan-beam tomography using divergent capacitive
      ultrasonic transducers.
AB  - Abstracttrasonic transducers (CUTs) with curved backplates was used to acquire
      signals through regions of air containing solid objects, air flow, and
      temperature fields. Fan-beam datasets were collected and used in a tomographic
      reconstruction algorithm to produce cross-sectional images of the area under
      interrogation. In the case of the solid objects, occluded rays from the
      projections were accounted for using a compensation algorithm and a priori
      knowledge of the object. A rebinning routine was used to pick out parallel ray
      sets from the fan-beam data. The effects of further reducing the number of
      datasets also were investigated, and, in the case of imaging solid objects,
      characteristic Gibbs phenomena were seen in the reconstructions as expected.
      However, when imaging temperature and flow fields, the aliasing artefacts were
      not seen, but the reconstructed values decreased with the size of dataset used.
      The effect of changing the kernel filter function also was investigated, with the
      different filters giving the best compromise between image noise, reconstruction
      accuracy, and amount of data required in each scenario.

PMID- 16463506
TI  - Numerical study of the spectral 3-D green's function singularities for
      piezoelectric SAW components.
AB  - This article deals with the numerical study of the singularities appearing in the
      spectral 3-D Green's function associated with the piezoelectric surface acoustic
      wave components (so-called SAW components). These electrical units are currently
      used today in several devices produced by the telecommunications industry (radio,
      TV, radar, and digital telecommunication systems). The need to improve their
      performance has motivated engineers and researchers to use mathematical modeling
      intensively, in particular the integral equations technique here used, which
      requires the computing of the associated Green's function and the study of its
      properties.

PMID- 16463507
TI  - Application of Taguchi robust design method to SAW mass sensing device.
AB  - It is essential that measurement systems provide an accurate and robust
      performance over a wide range of input conditions. This paper adopts Taguchi's
      signal-to-noise ratio (SNR) analysis to develop a robust design for the Rayleigh
      surface acoustic wave (SAW) gas sensing device operated in a conventional delay
      line configuration. The goal of the present Taguchi design activity is to
      increase the sensitivity of this sensor while simultaneously reducing its
      variability. A time- and cost-efficient finite-element analysis method is used to
      investigate the effects on the sensor's response output of variations in the
      carbon dioxide (CO2) gas deposited mass. The simulation results for the resonant
      frequency and wave mode analysis are all shown to be in good agreement with the
      values predicted theoretically.

PMID- 16463508
TI  - Investigation of electrostrictive polymers for energy harvesting.
AB  - The recent development of electrostrictive polymers has generated new
      opportunities for high-strain actuators. At the current time, the investigation
      of using electrostrictive polymer for energy harvesting, or mechanical to
      electrical energy conversion, is beginning to show its potential for this
      application. In this paper we discuss the mechanical and electrical boundary
      conditions for maximizing the energy harvesting density and mechanical-to
      electrical coupling of electrostrictive materials. Mathematical models for
      different energy harvesting approaches were developed under quasistatic
      assumptions. Energy harvesting densities then are determined for representative
      electrostrictive material properties using these models. Comparison with a
      magnetic-based energy harvesting system suggests that electrostrictive energy
      harvesting systems are preferable for "small" energy harvesting applications with
      low-frequency excitation.

PMID- 16463510
TI  - Assistants misrepresented as CDAs.

PMID- 16463509
TI  - Transducer for harmonic intravascular ultrasound imaging.
AB  - A recent study has shown the feasibility of tissue harmonic imaging (THI) using
      an intravascular ultrasound (IVUS) transducer. This correspondence describes the
      design, fabrication, and characterization of a THI-optimized piezoelectric
      transducer with oval aperture of 0.75 mm by 1 mm. The transducer operated at 20
      MHz and 40 MHz, and was comprised of a single piezoelectric layer with additional
      passive layers. The Krimholtz-Leedom-Matthaei (KLM) model was used to iteratively
      find optimal material properties of the different layers. The transducer
      characterization showed -6 dB fractional bandwidths of 30% and 25%, and two-way
      insertion losses of -20 dB and -36 dB, respectively.

PMID- 16463511
TI  - Another reason to use Blue Cross.

PMID- 16463512
TI  - "I'm from the government and I'm here to help".

PMID- 16463514
TI  - Stopping employees who deliberately provoke co-workers.

PMID- 16463513
TI  - Throwing away unsolicited dental supplies.

PMID- 16463515
TI  - "Sales" skills for young dentists.

PMID- 16463517
TI  - Crown lengthening: a second look.

PMID- 16463519
TI  - Year-end legislative wrap-up.

PMID- 16463520
TI  - Dentists can send a message to state government.

PMID- 16463521
TI  - Here's one way to expand access to Medicaid dental coverage.

PMID- 16463522
TI  - New law will improve access to care for underserved.

PMID- 16463523
TI  - The MAPS program: stopping "doctor shoppers".

PMID- 16463525
TI  - On the role of attention in naturally occurring matching relations.
AB  - Prior researchers have evaluated the efficacy of using the matching law to
      describe naturally occurring behavior-environment interactions. However, spurious
      matching could be obtained if the response and environmental event were
      correlated, even if the event did not reinforce the response. To assess the
      likelihood of obtaining spurious matching when relating attention and problem
      behavior, we evaluated the problem behavior of 3 participants for whom attention
      did not serve as a reinforcer for problem behavior in a functional analysis. Both
      the simple and generalized matching equations were used to examine matching
      relations extracted from descriptive observations that were conducted in the
      participants' classrooms. The results of aggregated matching analyses showed that
      the proportional rate of responding approximately matched the proportional rate
      of contiguous adult attention. Matching analyses conducted for all participants
      showed correlations between attention and problem behavior. These results
      demonstrate that spurious matching can be obtained, and they highlight the role
      of functional analyses in the analysis of naturally occurring matching relations.

PMID- 16463526
TI  - Derived manding in children with autism: synthesizing Skinner's verbal behavior
      with relational frame theory.
AB  - Mand functions for two stimuli (A1 and A2) were trained for 3 children with
      autism and were then incorporated into two related conditional discriminations
      (A1-B1/A2 -B2 and B1-C1/B2-C2). Tests were conducted to probe for a derived
      transfer of mand response functions from A1 and A2 to C1 and C2, respectively.
      When 1 participant failed to demonstrate derived transfer of mand response
      functions, transfer training using exemplars was conducted. When participants had
      demonstrated derived transfer of mand functions, the X1 and X2 tokens that were
      employed as reinforcers for mand responses were incorporated into two conditional
      discriminations (X1-Y1/X2-Y2 and Y1-Z1/Y2-Z2). Tests were conducted for derived
      transfer of reinforcing functions. Finally, tests were conducted to determine if
      the participants would demonstrate derived manding for the derived reinforcers
      (present C1 and C2 to mand for Z1 and Z2, respectively). Derived transfer of
      functions was observed when the sequence of training and testing was reversed
      (i.e., training and testing reinforcing functions before mand response functions)
      and when only minimal instructions were provided.

PMID- 16463527
TI  - Assessing the feasibility of using contingency management to modify cigarette
      smoking by adolescents.
AB  - Cigarette smoking is a leading cause of preventable death in the United States.
      Many smokers initiate this dangerous behavior during adolescence. This report
      describes a contingency management intervention designed to initate and maintain
      a period of abstinence from cigarettes by adolescent smokers. Results suggest
      that the intervention was generally successful and that further investigation of
      this topic is warranted.

PMID- 16463528
TI  - Effects of stimulus variation on the reinforcing capability of nonpreferred
      stimuli.
AB  - We examined the effects of stimulus (reinforcer) variation in several different
      contexts. In Study 1, we identified high-quality (HQ) and low-quality (LQ)
      stimuli based on results of a paired-stimulus assessment and examined their
      effects when available under concurrent-reinforcement schedules for 8
      participants. No participants showed preference for the LQ stimuli when compared
      singly or in a varied arrangement to the HQ stimulus. In Study 2, we identified
      nonpreferred (NP) stimuli based on results of a single-stimulus assessment and
      examined their effects when available under single-reinforcement schedules for 3
      participants. Results of Study 2 were mixed. One participant's data indicated
      that the varied presentation of NP stimuli produced a modest improvement in
      performance over that observed when the stimuli were presented singly. By
      contrast, a second participant's data showed no facilitative effect for the
      varied delivery of NP stimuli and that the inclusion of an HQ stimulus in the
      varied arrangement obscured the reinforcing effects of the HQ stimulus. The 3rd
      participant's data showed no effect for the varied delivery of NP stimuli but an
      apparent facilitative effect when an HQ stimulus was included in the varied
      arrangement, which was attributable solely to the presence of the HQ stimulus.

PMID- 16463529
TI  - Refining the experimental analysis of academic skills deficits: Part I. An
      investigation of variables that affect generalized oral reading performance.
AB  - Experimental analyses for improving reading fluency deficits have rarely targeted
      generalized increases in academic responding. As a consequence, the variables
      that may help students to generalize newly learned forms of academic responding
      like reading are not well understood. Furthermore, experimental analyses of
      reading fluency interventions have not systematically examined difficulty level
      as a variable that may affect instructional outcomes. The experiment reported in
      this paper expands (a) the measurement of the dependent variables to include
      generalized increases across tasks (reading passages) and (b) the combination of
      independent variables used to produce measurable generalized increases. The
      results demonstrate the importance of combining reward and instructional
      variables (including difficulty level) to produce generalized increases and how
      those variables can be meaningfully investigated prior to making treatment
      recommendations.

PMID- 16463530
TI  - An example of discovery research involving the transfer of stimulus control.
AB  - The initial purpose of the present study was to replicate procedures for teaching
      preschool children to recruit attention at appropriate times by having an
      experimenter signal the availability and unavailability of attention (i.e.,
      arrange a multiple schedule involving reinforcement and extinction; Tiger &
      Hanley, 2004). Following the development of discriminated social responding, the
      schedule-correlated stimuli were removed (i.e., a mixed schedule of reinforcement
      was arranged). However, discriminated responding continued during these
      conditions. Further evaluation suggested that stimulus control over children's
      social responding had transferred from the schedule-correlated stimuli to the
      delivery of reinforcement. The effect of a history of reinforcement under
      multiple-schedule conditions on performance under mixed schedules was then
      replicated with 2 participants in a reversal design. These findings suggest that
      following experience with schedule-correlated stimuli, these stimuli may be
      removed with only modest disruption to discriminated responding.

PMID- 16463531
TI  - Analysis of response repetition as an error-correction strategy during sight-word
      reading.
AB  - A great deal is known about the effects of positive reinforcement on response
      acquisition; by contrast, much less research has been conducted on contingencies
      applied to errors. We examined the effects of response repetition as an error
      correction procedure on the sight-word reading performance of 11 adults with
      developmental disabilities. Study 1 compared single-response (SR) repetition and
      multiple-response (MR) repetition, and results showed that all 6 participants
      acquired more sight words with the MR procedure. Study 2 compared MR error
      correction following every incorrect response (continuous) and following one
      third of incorrect responses (intermittent), and results showed that all 6
      participants acquired more sight words when error correction was continuous.
      Study 3 compared MR error correction in which errors required practice of the
      training word (relevant) versus a different word (irrelevant), and results showed
      that 3 of 9 participants showed better performance under the relevant condition;
      however, all participants showed improvement even under the irrelevant condition.
      Findings are discussed in terms of the behavioral processes by which error
      correction may enhance performance during acquisition.

PMID- 16463532
TI  - Biofeedback treatment of paradoxical vocal fold motion and respiratory distress
      in an adolescent girl.
AB  - In this investigation, we evaluated the effectiveness of surface electromyography
      (EMG) biofeedback to treat paradoxical vocal fold motion in a 16-year-old girl.
      EMG biofeedback training occurred once per week over the course of 10 weeks. In a
      changing criterion design, muscle tension showed systematic changes that
      corresponded with changes in the criterion. Overall, baseline muscle tension
      levels were reduced over 60%, with corresponding reductions in episodes of
      respiratory distress and chest pain. Subjective reports by the patient and the
      patient's mother indicated improvements in school attendance and overall adaptive
      functioning.

PMID- 16463533
TI  - Long-term benefits of prompts to use safety belts among drivers exiting senior
      communities.
AB  - Senior drivers are vulnerable to automobile crashes and subsequent injury and
      death. Safety belts reduce health risks associated with auto crashes. Therefore,
      it is important to encourage senior drivers to wear safety belts while driving.
      Using a repeated baseline design (AAB), we previously reported that motivating
      signs boosted safety belt usage by drivers exiting senior communities from
      baseline (72% and 68% usage), to postinstallation of signs (94%), to 6 months
      follow-up (80%). The current study was a 4-year follow-up in which six senior
      communities, with seat belt signs, were compared to six matched control senior
      communities with no signs. Safety belt usage was stable, across 4 years, at
      approximately 80% for both male and female drivers and front seat passengers for
      the six communities with signs, and was approximately 55% for control sites.
      These finding suggest that the simple and low-cost intervention of erecting signs
      to prompt safety belt use has persistent benefits that affect driver and
      passenger behavior alike.

PMID- 16463534
TI  - Functional analysis of self-injurious behavior and its relation to self
      restraint.
AB  - Some individuals who engage in self-injurious behavior (SIB) also exhibit self
      restraint. In the present study, a series of three functional analyses were
      conducted to determine the variables that maintained a participant's SIB, one
      without restraint items available, one with a preferred and effective form of
      self-restraint (an airplane pillow) available noncontingently, and one with this
      item delivered contingent on SIB. Results suggested that SIB was reinforced by
      escape and by access to self-restraint materials, self-restraint appeared to be
      maintained by automatic reinforcement, and continuous access to highly preferred
      restraint materials effectively suppressed SIB.

PMID- 16463535
TI  - Assessing object-to-picture and picture-to-object matching as prerequisite skills
      for pictorial preference assessments.
AB  - Tangible and pictorial paired-stimulus (PPS) preference assessments were compared
      for 6 individuals with developmental disabilities. During tangible and PPS
      assessments, two edible items or photographs were presented on each trial,
      respectively, and approach responses were recorded. Both assessments yielded
      similar preference hierarchies for 3 participants who could match pictures and
      objects but different hierarchies for 3 participants who could not. Reinforcer
      assessments verified that items identified as high preference on PPS assessments
      functioned as reinforcers only for participants with matching skills.

PMID- 16463536
TI  - Noncontingent reinforcement as treatment for food refusal and associated self
      injury.
AB  - We examined the use of noncontingent reinforcement to decrease self-injury and
      increase bite acceptance in a child who exhibited food refusal. First, a brief
      functional analysis suggested that self-injury was maintained by escape from food
      presentation. Next, we evaluated an intervention that involved noncontingent
      access to a video during feeding sessions. Results of the intervention showed a
      decrease in self-injury and an increase in bite acceptance.

PMID- 16463538
TI  - Self- and cross-citations in the Journal of Applied Behavior Analysis and the
      Journal of the Experimental Analysis of Behavior: 1993-2003.
AB  - Self- and cross-citations in JABA and JEAB from 1993 through 2003 were examined.
      Yearly mean levels of self-citation for JABA and JEAB were 34.9% and 33.2%,
      respectively. Overall, 7.8% of JABA citations were JEAB articles, and 0.6% of
      JEAB citations were JABA articles. The former value, but not the latter, is
      substantially higher than the cross-citation level reported for earlier years.
      The two JEAB articles most often cited in JABA were published over 20 years ago
      and are concerned with establishing operations and the matching law.

PMID- 16463537
TI  - Using a combined blocking procedure to teach color discrimination to a child with
      autism.
AB  - A combined blocking procedure was used to teach a child with autism to select two
      colors on request. First, two color cards were placed at fixed locations on a
      table and the experimenter repeatedly requested the child to touch one of the
      colors. After 10 consecutive correct selections, the child was asked to touch the
      other color. Blocks of trials with each color were systematically thinned until
      requests were presented randomly with few errors. Subsequently, the location of
      the selection cards was systematically alternated until the child was able to
      touch the correct card when both requests and card positions were presented in
      random fashion.

PMID- 16463539
TI  - The impact of uncertainty on phytoremediation project costs.
AB  - Pollution of the environment by metals and organic contaminants is an intractable
      global problem, with cleanup costs running into billions of dollars using current
      engineering technologies. The availability of alternative, cheap and effective
      technologies would significantly improve the prospects of cleaning-up metal
      contaminated sites. Phytoremediation has been proposed as an economical and
      'green' method of exploiting plants to extract or degrade the contaminants in the
      soil. To date, the majority of phytoremediation efforts have been directed at
      leaping the biological biochemical and agronomic hurdles to deliver a working
      technology, with scant attention to the economic outlook other than simple
      estimates of the cost advantages ofphytoremediation over other techniques. In
      this paper we use a deterministic actauarial model to show that uncertainty in
      project success (the possibility that full clean up may not be realized) may
      significantly increase the perceived costs of remediation works for decision
      makers.

PMID- 16463541
TI  - Assessing the potential of short rotation coppice (SRC) for cleanup of
      radionuclide-contaminated sites.
AB  - A small-scale greenhouse investigation was undertaken using Goat willow (Salix
      caprea) and aspen (Populus tremula) to evaluate the potential of short rotation
      coppice for remediation of 137Cs- and 90Sr-contaminated sites. Results showed
      that both species were able to accumulate these radionuclides from a
      representative disposal soil (aged) and a spiked soil S. caprea accumulating
      greater levels of 137Cs than P. tremula, with no difference between species for
      90Sr accumulation. For each radionuclide, the distribution in both species was
      similar, with 137Cs accumulation greatest in the roots, whereas 90Sr accumulation
      was greatest in the leaves. It was also evident that the soil-to-plant transfer
      factor (Tf) values for 90Sr were greater than for 137Cs, agreeing with
      differences in the reported bioavailailablity of these radionuclides in soil
      Based on the Tf values for S. caprea (conservative), estimated remediation times
      were 92 and 56 yr, for 137Cs and 90Sr, respectively. It is suggested that the
      selection of Salix species grown in a system of SRC provides a significant
      opportunity for removal of both 137Cs and 90Sr, primarily due to its higher
      biomass production. However, for 137Cs phytoremediation investigations into the
      appropriate use of soil amendments for increasing bioavailability are required.

PMID- 16463540
TI  - Beneficial role of hydrophytes in removing Cr(VI) from wastewater in association
      with chromate-reducing bacterial strains Ochrobactrum intermedium and
      Brevibacterium.
AB  - This study deals with the use of three chromium-resistant bacterial strains
      (Ochrobactrum intermedium CrT-1, Brevibacterium CrT-13, and CrM-1) in conjunction
      with Eichornia crassipes for the removal of toxic chromium from wastewater.
      Bacterial strains resulted in reduced uptake of chromate into inoculated plants
      as compared to noninoculated control plants. In the presence of different heavy
      metals, chromium uptake into the plants was 28.7 and 7.15% less at an initial
      K2CrO4 concentration of 100 and 500 microg ml(-1) in comparison to a metal free
      chromium solution. K2CrO4 uptake into the plant occurred at different pHs tested,
      but maximum uptake was observed at pH 5. Nevertheless, the bacterial strains
      caused some decrease in chromate uptake into the plants, but the combined effect
      of plants and bacterial strains conduce more removal of Cr(VI) from the solution.

PMID- 16463542
TI  - Species selection for phytoremediation of 36Cl/35Cl using angiosperm phylogeny
      and inter-taxa differences in uptake.
AB  - High concentrations of 35Cl and the radioisotope 36Cl (produced naturally by
      cosmic radiation and anthropogenically by U fission and the use of neutron
      sources) can be problematic in soil, but are potentially amenable to
      phytoremediation if appropriate plants can be found. Here, results are reported
      that might aid the selection of plants with unusually high or low uptake of 36Cl
      A residual maximum likelihood analysis was used to estimate, from 13 experiments,
      relative 36Cl uptake by 106 species across the angiosperm phylogeny. Nested
      analysis of variance, coded using a recent angiosperm phylogeny, showed that
      there were significant inter-species differences in 36Cl uptake and that species
      behavior was not independent; but linked through theirphylogeny. Eudicots had
      significantly higher 36Cl uptake than Monocots and related clades and, in
      particular the Orders Caryophyllales, Apiales, and Cucurbitales had high uptake
      while the Poales, Lillales, Brassicales, and Fabales had low uptake. Overall, 35%
      of the inter-taxa variation in 36Cl was attributed to the taxonomic ranks of
      Order and above, a significant phylogenetic effect compared with other elements
      for which similar analyses have been published. The implications of these
      findings for selecting plants for phytoremediation of soil contaminated with
      35/36Cl are discussed.

PMID- 16463543
TI  - Rapid plant-cover establishment on gold mine tailings in southern New Zealand:
      glasshouse screening trials.
AB  - The use of a short-term vegetation cover to temporarily control the negative
      environmental effects of inactive tailings ponds is notfrequently practiced
      during operational mining, but could have some merit This article reports on a
      glasshouse trial designed to examine some of the issues associated with short
      term vegetation: fast germination of a high proportion of seed, the ability of
      seedlings to survive in unamended substrates, and potentially toxic substrate.
      Five nonindigenous plant species were tested--barley (Hordeum vulgare), rye corn
      (Secale cereale), Italian ryegrass (Lolium multifiorum), red clover (Trifolium
      pratense), and lucerne (Medicago sativa)--in five different types of substrate:
      unamended tailings, tailings and fertilizer, tailings and greenwaste, biosolid
      blend compost, and local topsoil. The nutrient and heavy metal status (As, Cu,
      Cd, Ni, Pb) of each substrate type was determined Plant species performance was
      monitored over 14 wk Substrate metal concentrations were low except for As, which
      was elevated in all substrate types. Plants in unamended tailings grew less
      vigorously than plants in tailings and compost or in topsoil. Plant performance
      in tailings and fertiliser was greatly suppressed following a high fertilization
      rate. Metal uptake in plants was highest for As (0.4-77 mg kg(-1) DW) and Cu (5.3
      50.3 mg kg(-1) DW). Future field trials are necessary to authenticate findings,
      but barley and rye corn are promising species for a short-term tailings cover.

PMID- 16463544
TI  - Phytoextraction potential of the nickel hyperaccumulators Leptoplax emarginata
      and Bornmuellera tymphaea.
AB  - Leptoplax emarginata and Bornmuellera tymphaea are nickel hyperaccumulators of
      the Brassicaceae family endemic to serpentine soils in Greece. The aims of this
      work were to compare the growth and uptake behavior of these plants with the Ni
      hyperaccumulator species Thlaspi caerulescens and Alyssum murale, and to evaluate
      their effect on soil Ni availability. Plants were grown for 3 mo on three soils
      that differ in Ni availability. Ni availability in soils was measuredby isotopic
      exchange kinetics and DTPA-TEA extractions. Results showed that L. emarginata
      produced significantly more biomass than other plants. On the serpentine soil, B.
      tymphaea showed the highest Ni concentration in shoots. However,
      Niphytoextraction on the three soils was maximal with L. emarginata. The high
      initial Ni availability of soil Serp (470.5 mg kg(-1)) was the main explanation
      for the high Ni concentrations measured in plant shoots grown on this soil,
      compared to those grown on soils Calc and Silt A. murale was the least efficient
      in reducing Ni availability on the serpentine soil L. emarginata appeared as the
      most efficient species for Ni phytoextraction and decrease of the Ni available
      pool.

PMID- 16463545
TI  - Screening of sunflower cultivars for metal phytoextraction in a contaminated
      field prior to mutagenesis.
AB  - Sunflower can be used for the remediation of metal-contaminated soils. Its high
      biomass production makes this plant species interestingfor phytoextraction and
      using sunflower oil for a technical purpose may improve the economic balance of
      phytoremediation. The aim of the present field study was to screen 15 commercial
      cultivars of Helianthus annuus L. grown on metal-contaminated soil, to find out
      the variety with the highest metal extraction, which can be further improved by
      mutation or in vitro breeding procedures. Two different fertilizers (ammonium
      sulphate and ammonium nitrate) were also used to enhance the bioavailability of
      metals in soil Highly significant differences were observed within tested
      varieties for metal accumulation and extraction efficiency. Furthermore, ammonium
      nitrate increased cadmium extraction, whereas ammonium sulphate enhanced zinc and
      lead uptake in most tested cultivars. In this field-based sunflower screening, we
      found enhanced cumulative Cd, Zn, and Pb extraction efficiency by a factor 4.4
      for Salut cultivar. We therefore emphasize that prior to any classical breeding
      or genetic engineering enhancing metal uptake potential, a careful screening of
      various genotypes should be done to select the cultivar with the naturally
      highest metal uptake and to start the genetic improvement with the best available
      plant material.

PMID- 16463546
TI  - [New targets for cancer treatment].

PMID- 16463547
TI  - [Erlotinib. A new option for non-small cell lung cancer].

PMID- 16463548
TI  - [Medical treatment of vertigo].

PMID- 16463549
TI  - [Achieving eradication of MRSA colonization in patients. Therapeutic options].

PMID- 16463550
TI  - [Long QT interval. Interaction of terfenadine and itraconazole].

PMID- 16463552
TI  - [Bisphosphonate inhibits glucocorticoid-induced osteoporosis].

PMID- 16463551
TI  - [Interactions between drugs and micronutrients].

PMID- 16463553
TI  - [Ibandronate once a month].

PMID- 16463554
TI  - [What drug protect from dementia?].

PMID- 16463555
TI  - [Sleep apnea and cardiac insufficiency frequently associated].

PMID- 16463556
TI  - [Echinacea angustifolia is ineffective in an experimental study].

PMID- 16463557
TI  - [Migraine prevention with Petasites].

PMID- 16463558
TI  - [Cardiovascular diseases are a frequent cause of death].

PMID- 16463559
TI  - [Cost-effectiveness of dietetic measures for lowering blood pressure].

PMID- 16463560
TI  - [Proton pump inhibitors for high risk patient with stomach ulcer].

PMID- 16463562
TI  - [Epidemiology of chlamydia infections in youth and younger adults].

PMID- 16463561
TI  - [Ibuprofen is more effective and safer than paracetamol].

PMID- 16463563
TI  - [Gardner syndrome: clinical and epidemiologic up to date].
AB  - In 1950 EJ Gardner first described a new syndrome characterized by (1) familial
      colonic polyposis, (2) multiple osteomas, (3) soft tissues cysts and (4) fibrous
      lesions. Thereafter, in 1975 Watne and coll. have demonstrated the occurence, in
      patients affected by Gardner syndrome, of the early onset of osteomas and dental
      inclusions in maxillary bones. Gardner syndrome is actually considered a severe
      life treathening condition due to the poor quality of life and the evolutive
      pattern of colonic polyps to colon cancer in 100% of cases. The aim of this paper
      is the review of the pathophysiologic and clinical aspects of Gardner syndrome,
      with report of institutional clinical data about epidemiology and clinical
      presentation of such condition, attempting to elaborate a clinical protocol for
      early detection of that.

PMID- 16463564
TI  - [Child labour].
AB  - The authors emphasize the violation of children's and adolescents' rights as a
      result of the exploitation of child labour. Besides the legal aspect, they
      pointed out the medical features related to the delicate growing process of the
      child in the phases of development and adaptation of the main organs to hard
      work. Currently the problem is being supervised by those states that recognize
      the right for minors to be protected against any kind of physical, mental,
      spiritual and moral risk.

PMID- 16463565
TI  - [Paraneoplastic syndromes: a review].
AB  - Modern oncology often obtains good results against earlier neoplasms, whilst it's
      still in difficulties against the advanced ones. The knowledge of paraneoplastic
      syndromes is crucial both to cure patients and to do an earlier diagnosis. When
      we recognize a paraneoplastic syndrome that comes before the clinic beginning of
      a neoplasm, perhaps we save a life. This review discusses all the main
      paraneoplastic syndromes, focusing mainly on their clinical aspect and reminding
      the most commonly associated cancers.

PMID- 16463566
TI  - [Pregnancy and work].
AB  - In the last decades there has been an increase of women's presence in the working
      field. That has been a consequence of the use of an advanced technology, of a
      different organization of work, of the rules about men/women equality, as wellas
      of the women's emancipation. As a result women have been exposed to a greater
      amount of risks both for their health and for their reproductive function. In
      this work, we highlighted the pathogenic effects resulting from the interaction
      of different substances present in the working place with the female organism,
      with special interest in the effects on pregnancy. Furthermore, we laid stress on
      the rules and on the guidelines that safeguard women's right to work as well as
      their right to be mothers both at a national and at an european level.

PMID- 16463567
TI  - [New perspectives in organ transplantations].

PMID- 16463568
TI  - [Metastatic breast cancer: new chemotherapy regimens with taxanes].
AB  - Patients with breast cancer are frequently treated with anthracyclines and/or
      taxanes, which are among the most useful agents in this disease. Therefore, it is
      increasingly difficult to find active regimens in heavily pretreated patients.
      Gemcitabine is a cytosine arabinoside prodrug analog which shows significant
      activity, as single agent, in metastatic breast cancer. The combination of
      gemcitabine and taxanes is particularly valuable because of the different
      mechanisms of action of each drug and their non-everlapping toxicities. During
      the last years, we have carried out several trials with gemcitabine in
      combination with either docetaxel or paclitaxel. The combination of gemcitabine
      and docetaxel in 53 previously treated patients resulted in 53% response rate
      (RR) with a median time to progression of 7.5 months, and an overall survival of
      16.5 months. When gemcitabine was combined with paclitaxel in a biweekly schedule
      in 34 evaluable patients with prior exposure to several chemotherapy regimens, RR
      was 53%. It was 50% in patients previously treated with docetaxel. Toxicity was
      generally mild to moderate. Paclitaxel plus gemcitabine given as an every 2-weeks
      schedule is a practical, well tolerated and active regimen in advanced breast
      carcinoma, which deserves further evaluation in less heavily pretreated patients.

PMID- 16463569
TI  - Oral health of individuals aged 3-80 years in Jonkoping, Sweden during 30 years
      (1973-2003). I. Review of findings on dental care habits and knowledge of oral
      health.
AB  - The aim of the present study was to compare data on dental care habits and
      knowledge of oral health in four cross-sectional epidemiological studies carried
      out in 1973,1983,1993, and 2003. The 1973 study constituted a random sample of
      1,000 individuals evenly distributed in the age groups 3, 5, 10, 15, 20, 30, 40,
      50, 60, and 70 years. The same age groups with addition of a group of 80-year
      olds were included in the 1983, 1993 and 2003 studies, which comprised 1,104,
      1,078, and 987 individuals, respectively. A questionnaire about dental care
      habits and knowledge of oral health was used in connection with a clinical and
      radiographic examination. The same questions were used in all the four studies.
      An addition to the 1993 and 2003 investigations were questions concerning ethnic
      background. In 2003 approximately 90-95 per cent of all individuals were visiting
      the dentist on a regular basis every or every second year. The 30- and 40-yea r
      olds, however, did not visit a dentist as regularly in 2003 as in 1993. In these
      age groups 21-24 per cent of the individuals, respectively, reported that they
      had not visited a dentist in the last 2 years. Almost all children 3-15 years old
      received their dental care within the Public Dental Service (PDS). During the
      period 1973-2003 an increase in percentage of individuals aged 20-50 years
      treated by the PDS was seen compared to private practice, while among 60-80 year
      olds there were only minor changes. Most so-year-olds and older received their
      dental care by private practitioners. About 70-80 per cent of all adults in 2003
      were enrolled in a recall system on the dentist's initiative while in 1973 most
      appointments were based on the patient's own initiative. The number of
      individuals who were frightened, 5-17 per cent, or felt discomfort at the
      prospect of an appointment with the dentist was more or less the same during the
      whole period. The knowledge of the etiology of dental diseases did not changed
      much between 1973 and 2003. The frequency of toothbrushing increased since 1973
      and in 2003 more than 90 per cent of all individuals brushed their teeth twice or
      once a day. The use of dental floss and toothpicks decreased in 2003 compared to
      1983 and 1993. Almost all individuals in 2003 used fluoride toothpaste. It was
      obvious that the dental team constituted the main source of dental health
      information. For the age groups 20 and 30 years information from friends and
      relatives was also important. In the age groups 3-20 years up to 45 per cent of
      the individuals were consuming soft drinks every day or several times a week.

PMID- 16463571
TI  - [Natural history of Avian Influenza or "chicken flu". Present and future health
      analysis].
AB  - A review and update about a new zoonosis, as it is the Avian Influenza or
      "poultry grippe" has been made. This disease is endemic in the Southeast of Asia
      and continues at present time, being active in Vietnam and Tailand. We have
      considered the Natural History of the Avian Influenza and specifically the late
      epidemies, starting from the one in 1997 in Hong Kong, in which an Orthomyxovirus
      type A, subtype H5N1, broke the interespecies barrier. A health analysis is made,
      both for the present moment and the future, about the possibility of a World
      pandemic flu, originated by the mentioned Orthomyxovirus type A, agent of the
      Avian Influenza of highly virulent specificic virus strain pathogenic for men.
      The most favourable fact, among others, to deny the possibility of a future
      pandemic flu is the stability of H5N1 strain in both epidemics of poultry in Hong
      Kong and in the Southeast of Asia.

PMID- 16463570
TI  - Oral health of individuals aged 3-80 years in Jonkoping, Sweden during 30 years
      (1973-2003). II. Review of clinical and radiographic findings.
AB  - The aim of this epidemiological study was to analyze various clinical and
      radiographic data on oral health and compare the results to those of three cross
      sectional studies carried out in 1973 and 1983, and 1993. In 1973, 1983, 1993,
      and 2003 a random sample of 1,000; 1,104; 1,078; and 987 individuals,
      respectively, were studied. The individuals were evenly distributed in the age
      groups 3, 5, 10, 15, 20, 30, 40, 50, 60, 70, and 80 years. In 1973 80-year-olds
      were not included. All subjects were inhabitants of the City of Jonkoping,
      Sweden. The clinical and radiographic examination assessed edentulousness,
      removable dentures, implants, number of teeth, caries, restorations and
      overhangs, oral hygiene, calculus, periodontal status, endodontic treatment, and
      periapical status. The number of edentulous individuals in the age groups 40-70
      years was reduced from 16 per cent in 1973 to 8 per cent in 1993, and to 1 per
      cent in 2003. The mean number of teeth increased, and up to the age of 60 years,
      individuals had more or less complete dentitions. During the 30-year period,the
      number of carious lesions and restorations decreased in general. In the 15-year
      olds the decrease in number of restored tooth surfaces was 900 per cent and the
      corresponding figure for 30-year-olds was 79 per cent. The age groups 60-800
      years showed an increase in number of restored tooth surfaces and had as a mean
      50 filled tooth surfaces. The oral health among 3-5-year-olds improved markedly
      between 1973 and 1993. In 2003, however, there was no further improvement in 3-
      and 5-year-olds compared to 1993. Generally, restorations in 2003 exhibited a
      high quality and 90-95 per cent had no proximal overhangs. In 1973 this figure
      was about 60 per cent. In the age groups 20-50 years there were continuously
      fewer teeth fitted with crowns or bridges during the 30-year period. In 1973 the
      50-year-olds had a mean of 24.5 per cent of the teeth crowned and in 2003 6.8
      percent. Compared to data from 1973 there was a reduction by half concerning
      occurrence of plaque and gingivitis in 2003. The frequency of individuals with
      one or more periodontal pockets (> or = 4 mm) increased with age. In 2003 the
      bone level at the age of 60 years corresponded to the bone level at the age of 40
      years in 1973. The percentage of endodontically treated teeth was lower in 2003
      in all age groups compared to 1973, 1983, and 1993. The percentage of
      endodontically treated teeth with periapical orjuxtaradicular destructions was
      generally lower in 2003 than in the earlier surveys, about 20 per cent in 2003
      compared to 25-30 per cent in 1973,1983, and 1993. The comparison of the four
      studies shows that there has been a great overall improvement in oral health over
      this 30-year period.

PMID- 16463572
TI  - [Dark matter and dark energy of the universe].
AB  - At the turn of the 20th Century, the Universe was thought to consist of our solar
      system, the Sun, planets, satellites and comets, floating under the Milky Way.
      The astronomers were ignorant of the existence of galaxies, clusters, quasars and
      black holes. Over the last ten years the Cosmology has made remarkable progress
      in our understanding of the composition of the Universe: 23 per cent is in an
      unknown form called dark matter; 73 per cent in another form called dark energy;
      3 per cent is made of free hydrogen and helium atoms; 0.5 per cent makes up all
      the light we see in the night including the stars, clusters and superclusters;
      0.3 per cent is in free neutrino particles; and finally, 0.03 per cent is in the
      heavier nuclei of which the Sun, the Earth and ourselves are made. In this work
      we study specially the dark matter and the dark energy. The first one appears to
      be attached to galaxies, and astronomers agree that it is cold, meaning that the
      particles that make up that matter are not moving fast. Very recently astronomers
      discovered that a tremendous amount of the so-cahled dark energy exists and that
      it is pushing and accelerating the expansion of the Universe. Should this
      expansion continue for another 14,000 million years, the sky will darken with
      only a handful of galaxies remaining visible.

PMID- 16463573
TI  - [Obituary session in memory of Luis Cifuentes Delatte (1907-2005)].

PMID- 16463574
TI  - [Knowing, knowledge and wisdom. The elderly and the master].
AB  - The concepts of knowing, knowledge and wisdom are analyzed through ones own
      respect and psychological foundations, accepting knowing as the consequence of
      immediate information, the knowledge as the elaborated intellectual concepts of
      knowing and wisdom as a superior category of intellectual and moral content.
      Outling these concepts, they are applied in real life through the elderly and
      through master.

PMID- 16463575
TI  - [Environmental contamination and children].
AB  - Environmental contamination is a growing problem and a major worldwide concern.
      Industrialization and overpopulation underlie it's first origins. Contamination
      has severe outcomes for the whole planet, and very particularly for mankind. But
      these consequences are specially ominous for childhood. Childs are more
      extensively exposed to contaminants than adults, for a longer period of time, and
      the effects are more deleterious as they act during the period of growth and
      development Concerning the risks associated to contaminants there is still a
      large paucity of data, particularly as referred to low grade exposure.

PMID- 16463577
TI  - [Effect of monosodium glutamate given orally on appetite control (a new theory
      for the obesity epidemic)].
AB  - Monosodium glutamate is a substance widely used as flavouring agent in the whole
      world. It is considered to be innocuos by the health agencies of North America
      and Europe. The effects of the oral administration of two dosages of MSG during
      the second half of pregnancy and all The developmental process of pups on
      appetite control and various hormones has been analysed in rats. Effects have
      been compared with the neonatal parenteral administration of the same compound.
      The structure of the arcuate nucleus of the hypothalamus has been investigated as
      well as plasma levels of GH, IGF-1 and leptin and its influence on food
      consumption. Measurements were performed at 30 and 90 days of life. A nearly
      total destruction of the arcuate nucleus can be observed with the parenteral
      administration of MSG but also with the highest oral dose. Significant reductions
      can be seen in plasma GH and IGF 1 levels at 30 days of life, that are partially
      recovered at 90 days. Plasma leptin levels are significantly reduced at 90 days
      of life with the two oral doses together with a significant increase in food
      intake. In conclussion, oral administration of MSG during pregnancy and
      development in rats is able to significantly affect hypothalamic control of
      various hormones and increases appetite.

PMID- 16463576
TI  - [The adipocyte, prodigious cell].
AB  - In this work, I stand out the rich endocrine role of adipocytes, that together
      with its function of lipidic deposit and regulating of metabolism, this confers
      them a central place in physiology and pathology.

PMID- 16463578
TI  - The idea is more important than the experiment.
AB  - Experimental science needs both idea and rigorous technical methodology. Modern
      science has the ability to measure with great ease and accuracy. There is a
      danger that this facility leads to the proliferation of experiments that are
      performed for the sake of measurement and not driven by idea. It is proposed that
      creative idea is best produced in an atmosphere of freedom to challenge the
      wisdom of the past. Teams that are multidisciplinary and cross cultures may
      produce the best ideas. Science should reanalyse the importance of quality of
      idea in science and the conditions in society that produce it.

PMID- 16463579
TI  - [Human herpesvirus 6 and multiple sclerosis].
AB  - In this work the possible etiologic relationship among the multiple sclerosis and
      the herpesvirus 6 (VHH-6) has been studied, subject debated in the last years.
      They have been carried out two studies using blood and LCR of sick of multiple
      sclerosis, and control in healthy fellows and with other neurological illnesses.
      The followed techniques are described to isolate the virus, their DNA, and the
      antibodies IgG and IgA in front of the VHH-6. The presente of the VHH-6 has not
      been demonstrated neither of its DNA in any case, but if it has been proved, with
      statistical significance that in the sick persons with buds of multiple
      sclerosis, the antibodies of the type IgG, as much in plasm as in LCR, was more
      present and in higher levels that in the controls.

PMID- 16463580
TI  - [New diagnostics based on the advances of the molecular biology].
AB  - Due to the advance of the new technologies of molecular biology, an exposition of
      the most recent is made (reaction in chain of the polimerasa, sequence and
      microarrays), and its application is commented in the field of the clinical
      medicine, of the pharmacology, and mainly, of the centers of diagnostic,
      especially in microbiology. Above all it, they think about an entire series of
      challenges and problems to solve, but some new expectations also open up with the
      creation of new services, introduction of new professionals no doctors and
      amplification of the diagnostic capacity.

PMID- 16463581
TI  - The new clearance method for hepatic diagnostics.
AB  - New multiparametric analysis and method of their evaluation were derived. The
      bolus dye injection is used for evaluation of ICG (indicyaningreen) and BSP
      (bromsulphophtalein) kinetics. This arrangement is a form of spectrophotometric
      measurement of BSP in plasma and/or pulse dye densitometry of ICG. Clearance
      values enable to differentiate liver diseases and to add their clinical staging.
      Pathophysiology of dye kinetics is discussed from two points of view i.e.
      sinusoidal and canalicular membrane transfer.

PMID- 16463582
TI  - Aortic cannulation and cardiopulmonary bypass independently produce selective
      brain lesions in pig.
AB  - Whether cardiopulmonary bypass alone or together with the manipulation of the
      aorta produce neurological complication remains controversial. Using a domestic
      pig model of cardiopulmonary bypass, we investigated the immediate effects of
      aortic cannulation and cardiopulmonary bypass on neuronal injury in different
      brain regions. We compared the presence of neuronal injury in three experimental
      groups: non-operated controls (n = 3); operated controls with aortic cannulation
      without cardiopulmonary bypass (n = 5); operated animals undergoing
      cardiopulmonary bypass (n = 5). Pyknotic cells were counted in the prefrontal
      cortex, cerebellum and in the hippocampal formation. Calretinin
      immunohistochemistry was used to show possible ischemic damages in the
      hippocampus which is known to be one of the most sensitive brain regions to
      ischemia. Decreased calretinin immunoreaction and reduced number of calretinin
      positive neurons were observed in the hippocampal dentate gyrus following aortic
      cannulation or cardiopulmonary bypass compared to the non-operated control group.
      Changes were more severe following cardiopulmonary bypass than after cannulation
      of the aorta alone. The frequency of pyknotic cell nuclei was not different in
      the control and experimental groups. Our experimental study suggests that both
      cannulation of the aorta alone and cardiopulmonary bypass affect a selected
      population of neurons.

PMID- 16463583
TI  - Lipoperoxidative activities in the cerebral cortex and medulla oblongata, related
      to age, sex, oxygen deficiency and short-term fasting.
AB  - In albino rats (Wistar), aged 10 and 14-days of postnatal life, experiments were
      performed, in which the intensity of lipoperoxidative processes in cerebral
      cortex and medulla oblongata in four experimental series was measured and
      compared: a) between females and males (control group); b) between females and
      males exposed to the hypobaric hypoxia (corresponding to the altitude of 7000 m
      and lasting 20 minutes); c) between females and males exposed to the short-term
      starvation (for 24 h between the day 5th and 6th of postnatal life); d) between
      females and males exposed to the combination of short-term starvation and
      hypobaric hypoxia. No sex-dependent differences in control measurements could be
      detected. The hypobaric hypoxia evokes significantly greater increase in
      lipoperoxidative processes in brain tissue of males as compared with females. The
      short-term starvation affected more the oxygen radicals production in the brain
      of females. Finally--the short-term starvation and the subsequent hypoxic stress
      did not evoke the sex-dependent differences in the brain of 10-day-old rats; in
      14-day-old females the higher values in brain cortex, in males higher values in
      medulla oblongata were established. The different sensitiveness to mentioned
      stressors in males (more sensitive to oxygen deficiency) and in females (more
      sensitive to nutritional deficiency) was described.

PMID- 16463585
TI  - Intermittent hypobaric hypoxia during development--morphological and functional
      changes in the neocortex.
AB  - Infant rats, together with their mother, were exposed to the simulated altitude
      of 7,000 m for 8 hours per day since birth to the age of 17 days. Animals were
      studied the 25th day, 8 days after the last exposure to hypoxia. The experimental
      and control animals were sacrificed the 25th day by the transaortic perfusion
      with 4% buffered neutral formaldehyde under ether anaesthesia. Brains were
      processed for classical neurohistological analysis (Nissl staining), Fluoro-Jade
      B and Hoechst. Cortical area in the AP plane 3 mm posterior to bregma was
      subjected to quantification and "laminar analysis" of the neurones count. The
      findings were as follows: a) The cytoarchitectonics of the brain in animals
      exposed to hypoxia was not severely damaged. b) The thickness of neocortex is in
      the experimental animals lower than that in the controls. c) The "laminar
      analysis" of neocortex showed a relative increase of neuronal density in layers
      I., II., V. and VI. of the cortex. d) The electrical stimulation of sensorimotor
      cortex 8 days after the end of hypoxia brought about prolongation of evoked
      cortical after discharges. These results demonstrate that the intermittent
      hypobaric hypoxia has a profound effect on morphological maturation of the
      central nervous system in infant rats. Hypoxia influenced the excitation--
      inhibition mechanisms of cortical neurones.

PMID- 16463584
TI  - NADPH-diaphorase positive neurons of the rat hippocampal formation: regional
      distribution, total number and colocalization with calcium binding proteins.
AB  - The present study aimed to asses the total number and distribution of the NADPH
      diaphorase-positive non-pyramidal neurons in Ammon's horn and dentate gyrus of
      rat hippocampal formation. Cell bodies were counted according to the "disector"
      principle. The total numbers varied from 27 000 to 32 400. In all strains,
      approximately one third of the NADPH-diaphorase-reactive non-principal cells were
      found in the dentate gyrus and the remaining two thirds were within the Ammon's
      horn. Analysis of the dorsoventral differences revealed that approximately 70% of
      NADPH-diaphorase-positive cells were in the dorsal and 30% in the ventral
      hippocampus. Distribution of NADPH-diaphorase-reactive cells in the different
      layers of the dentate gyrus and Ammon's horn was similar in all strains. Double
      labelling studies revealed colocalization of NADPH-diaphorase with calretinin,
      but none with calbindin or parvalbumin. NADPH-diaphorase-positive neurons appear
      to form the largest chemically identified subpopulation of the GABAergic
      inhibitory cell population of the hippocampal formation.

PMID- 16463586
TI  - Does electron microscopy change the view of the diagnosis of IgA nephropathy?
AB  - Our study is aimed to reveal the frequency and clinical significance of the
      coincidence of two widely spread entities, e.g. minimal change disease (MCD) and
      IgA nephropathy (IgAN), claimed to be found in an overwhelming number in some
      Asian regions. We retrospectively analyzed clinical and histological data from
      627 renal biopsies, performed in our department from January 2002 to January 2005
      and completed electron microscopy in 112 specimens diagnosed as IgAN. The
      coincidence of IgAN and MCD was found in 8 patients (7.1%). The coincidence of
      IgAN and minimal change nephrotic syndrome (MCNS) clinically--especially presence
      of nephrotic syndrome and the response to drug therapy (with corticosteroids)-
      behaves as "pure" MCN. Our data from Czech Republic seem to suggest that the
      combination of IgAN with MCNS can be found relatively frequently not only in
      Asian patients (as stressed by some authors of Asian origin) but also in European
      inhabitants. The pathogenesis of the coincidence of IgAN and MCD needs to be
      elucidated by further studies.

PMID- 16463587
TI  - Our experience with antidepressant treatment in the obese and type 2 diabetics.
AB  - We established depressive symptoms prevalence in 100 patients recommended to our
      obesity clinic and we started antidepressant treatment in 41 of them. It has been
      noted that administration of SSRI leads to weight reduction after 6 months, but
      is followed by a weight increase later. Our experience shows that 12 months long
      administration of bupropion and tianeptine leads to continuous weight loss.
      Antidepressant administration leads to an increase in pharmacotherapy adherence,
      which is significantly higher than in diet and psychotherapy alone. In diabetics,
      antidepressants reduce glucose levels, too. Their influence on weight and
      diabetes compensation is, however, smaller than in "classic" anti-obesity drugs,
      sibutramine and orlistat.

PMID- 16463588
TI  - Carnitine concentrations in term and preterm newborns at birth and during the
      first days of life.
AB  - Carnitine plays an important role in energetic metabolism. The aim of the study
      was to characterize the carnitine status in term and preterm newborns with
      respect to gestational age, birth weight, haematocrit and red blood cell count
      (RBC). The effect of nutrition on carnitine levels in the first week of life was
      also studied. Total blood pool of free carnitine (FC), acylcarnitines (AC) and
      total carnitine (TC) were analysed in whole cord blood and postnatally in
      capillary blood obtained at the day 4-6 in 33 term newborns and at the day 7-10
      in 27 preterm newborns using tandem mass spectrometry. Plasma level of carnitine
      in the cord blood was measured using radioenzymatic method. Cord plasma levels of
      FC, AC and TC were higher in preterm newborns in comparison with term newborns (p
      < 0.01), but the total blood pool of FC and TC in whole cord blood was lower in
      preterm newborns than in term newborns (p < 0.01) and positive correlation was
      found between FC and gestational age or birth weight (p < 0.05). In addition,
      positive correlation was found between AC and red blood cell count or haematocrit
      (p < 0.05). During the first week of life, blood pool of FC and TC in term
      newborns and AC and TC in preterm newborns decreased regardless of the type of
      enteral or parenteral nutrition. Our results indicate that preterm newborns are
      born with limited carnitine store. Interpretation of carnitine analyses in whole
      blood relies in addition to gestational age and birth weight on the haematocrit,
      especially in newborns with anaemia or blood hyperviscosity.

PMID- 16463589
TI  - The disease of Franz Kafka.
AB  - On June 3, 2004, 80 years have passed since the death of one of the greatest and
      the most important world writers of 20th century, the Prague German writer Franz
      Kafka. On November 5, 2004 we reminded that remarkable anniversary, which was
      also the 3rd anniversary of revelation of the monument of Franz Kafka in
      Tatranske Matliare, the High Tatras. Franz Kafka suffered from lung tuberculosis
      from 1917 until his death 1924. He was treated on lung tuberculosis in the
      sanatorium "Villa Tatra" from December 20, 1920 until August 27, 1921 in
      Tatranske Matliare, the High Tatras. Lung tuberculosis was a very dangerous
      disease in that time and the treatment by dietotherapy, climatotherapy and
      symptomatic therapy without antituberculotic drugs was less effective in many
      patients. In the paper the disease of Franz Kafka was described according to
      available literature.

PMID- 16463590
TI  - 60 years of the Third Medical Department of the First Faculty of Medicine and
      General Teaching Hospital.

PMID- 16463591
TI  - A comparison of family functioning, life and marital satisfaction, and mental
      health of women in polygamous and monogamous marriages.
AB  - BACKGROUND: A considerable body of research concludes that the polygamous family
      structure has an impact on children's and wives' psychological, social and family
      functioning. AIMS: The present study is among the first to consider within the
      same ethno-racial community such essential factors as family functioning, life
      satisfaction, marital satisfaction and mental health functioning among women who
      are in polygamous marriages and women who are in monogamous marriages. METHOD: A
      sample of 352 Bedouin-Arab women participated in this study: 235 (67%) were in a
      monogamous marriage and 117 (33%) were in a polygamous marriage. RESULTS:
      Findings reveal differences between women in polygamous and monogamous marriages.
      Women in polygamous marriages showed significantly higher psychological distress,
      and higher levels of somatisation, phobia and other psychological problems. They
      also had significantly more problems in family functioning, marital relationships
      and life satisfaction. CONCLUSION: The article calls on public policy and social
      service personnel to increase public awareness of the significance of polygamous
      family structures for women's wellbeing.

PMID- 16463592
TI  - Recovery from depression: a two-year follow-up study of general population
      subjects.
AB  - BACKGROUND: The recovery from depression and factors associated with it are not
      well known in the general population. AIMS: To conduct a two-year follow-up of
      general population subjects and investigate their recovery from depression.
      METHODS: Individuals who were assessed as suffering from depression on the basis
      of Beck Depression Inventory (BDI) scores were monitored for two years. RESULTS:
      Sixty-five per cent were still depressed after two years of follow-up. Negative
      life events had occurred more often in those who had remained depressed than in
      the others. Logistic regression analysis revealed that a high initial BDI score
      and a worsening of a subject's economic situation during the follow-up period
      were associated with failure to recover. Lack of use of health services was
      associated with non-recovery. CONCLUSION: Depression may be more chronic in the
      general population than previously has been thought.

PMID- 16463593
TI  - Psychological distress among recent Russian immigrants in the United States.
AB  - BACKGROUND: The purpose of this study was to examine the psychological status of
      Russian immigrants who have recently come to the United States. AIMS: The project
      included creation of a Russian version of the Hopkins Symptom Checklist-25 (HSCL
      25) in order to identify anxiety and depression in members of the Russian
      speaking immigrant population. METHODS: Translation and adaptation included (a)
      cross-cultural adaptation; (b) translation; (c) pre-testing; and (d) analysis of
      validity, reliability and internal consistency. Seventeen Russian-speaking
      patients at a Russian psychiatric clinic were recruited for the study and were
      compared with a sample of 42 Russian-speaking members of the community. RESULTS:
      The instrument showed internal consistency when evaluated with coefficient alpha.
      Clinic patients had significantly higher anxiety and depression symptom scores
      than community subjects. Russian immigrants' scores on the anxiety and depression
      scales were less than comparative data for the United States and notably less
      than similar measures for Russian immigrants to Israel. CONCLUSIONS: Recent
      Russian immigrants to the United States appear to have low prevalences of anxiety
      and depression.

PMID- 16463594
TI  - Ethnicity versus migration: two hypotheses about the psychosocial adjustment of
      immigrant adolescents.
AB  - STUDY BACKGROUND AND AIMS: This study investigates the psychosocial adjustment of
      immigrant adolescents and examines two hypotheses: the ethnicity hypothesis,
      which suggests that ethnic background determines the psychosocial reactions of
      immigrant adolescents; and the migration hypothesis, which suggests that the
      migration experience determines such reactions. METHODS: The study compared four
      groups of respondents: first-generation immigrants (N = 63) and second-generation
      immigrants (N = 64) from the former Soviet Union (FSU) in Israel; and Jewish (N =
      212) and non-Jewish (N = 184) adolescents in the FSU. A self-report questionnaire
      administered to the respondents collected demographic, educational and
      psychological data using standardised scales. RESULTS: Immigrant adolescents
      reported higher psychological distress, lower self-esteem and higher alchohol
      consumption than non-immigrant adolescents. Second-generation immigrants
      generally showed a higher level of functioning than first-generation immigrants.
      These findings favor the migration hypothesis. CONCLUSIONS: Our findings support
      the widely accepted view of migration as a potentially distress-provoking
      experience. They suggest that psychological reactions of immigrant adolescents,
      and in fact all immigrants, are best interpreted as reactive and are related to
      the universal stressful qualities of the migration experience. Further
      multiethnic comparative studies, however, are needed to confirm and refine these
      findings.

PMID- 16463595
TI  - Living arrangements of individuals with schizophrenia in Japan: impact of
      community-based mental health services.
AB  - AIMS: In Japan psychiatric hospitals and family play the predominant roles in
      caring for people with serious mental illness. This study explored how the
      introduction of community-based care has changed this situation by examining
      living arrangements of individuals with schizophrenia who were treated in one of
      the most progressive systems in Japan (Kawasaki) compared with national norms.
      METHODS: The proportion of clients with schizophrenia in the community versus
      hospital and living arrangements for those in the community were compared between
      the Kawasaki and national treated population, using data from the Kawasaki
      psychiatric service users survey in 1993 and two national surveys in 1993 and
      1983. The variation in living arrangements was examined across five different age
      cohorts. RESULTS: The estimated national population was 36.7, which was similar
      to 32.7 clients per 10,000 population in Kawasaki. Some 71% of the Kawasaki
      clients were treated in the community compared with 55% nationally. The
      difference between the Kawasaki and national populations was the largest among
      clients aged 40 to 59. The Kawasaki community clients had a higher proportion of
      clients living alone. CONCLUSIONS: The community mental health services available
      in Kawasaki appeared to reduce hospitalisation and help clients to live alone in
      the community.

PMID- 16463596
TI  - Rates and factors associated with suicide in Kaniyambadi Block, Tamil Nadu, South
      India, 2000-2002.
AB  - BACKGROUND: Inefficient civil registration systems, non-report of deaths,
      variable standards in certifying death and the legal and social consequences of
      suicide are major obstacles to investigating suicide in the developing world.
      OBJECTIVE: The aim of this study was to prospectively determine the suicide rate
      in Kaniyambadi Block, Tamil Nadu, South India, for the years 2000-2002 using
      verbal autopsies. METHOD: The setting for the study was a comprehensive community
      health programme in a development block in rural South India. The main outcome
      measure was death by suicide, diagnosed by a detailed verbal autopsy and census,
      and birth and death data to identify the population base. RESULTS: The average
      suicide rate was 92.1 per 100,000. The ratio of male to female suicides was
      1:0.66. The age-specific suicide rate for men increased with age while that for
      women showed two peaks: 15-24 years and over 65 years of age. Hanging (49%) and
      poisoning with organo-phosphorus compounds (40.5%) were the commonest methods of
      committing suicide. Acute and/or chronic stress was elicited for nearly all
      subjects. More men suffered from chronic stress while more women had acute
      precipitating events (chi2 = 4.58; p < 0.04). People less than 44 years of age
      had more acute precipitating events before death while older subjects reported
      more chronic stress (chi2 = 17.38; p < 0.001). CONCLUSION: The study replicates
      findings of an earlier study from the area. The suicide rate documented in this
      study is very high and is a major public health concern. There is a need for
      sentinel centres in India and in developing countries to monitor trends and to
      develop innovative strategies to reduce deaths by suicide.

PMID- 16463597
TI  - Psychiatry through the ethnographic lens.
AB  - The title of this article is deliberately chosen and reflects its agenda: to
      outline the contribution of ethnography to psychiatry. Ethnography is the study
      of culture through intensive participation, observation and listening. The
      postmodernists remind us that it is also the writing of culture (literally
      translated from the Greek). And in focusing on the writing of ethnographic texts
      they have alerted us to the problematic nature of transferring observation and
      experience into text. But an ethnographic account of psychiatry is possible only
      to the extent that we accept that psychiatry and the illnesses with which it
      deals are parts of culture. Anthropologists have long argued that psychiatric
      theory and practice are best understood using the same interpretive tools as are
      applied to other areas of cultural life, be it religion, cosmology or magic.

PMID- 16463598
TI  - The coming crisis in access to oral health care.

PMID- 16463600
TI  - Cri du Chat syndrome: a case report.
AB  - Cri du Chat Syndrome occurs as a result of a partial deletion in the short arm of
      chromosome 5. Among the consequent abnormalities are low birth weight, a striking
      catlike cry in infancy, mental retardation, epicanthal folds, hypertelorism and
      dental malocclusions. This paper presents a case report on the dental treatment
      of a 23-year-old patient who received multidisciplinary treatment, including
      special education and precocious stimulation for carriers of this syndrome.

PMID- 16463599
TI  - The influence of dental insurance on institutionalized older adults in ranking
      their oral health status.
AB  - To assess whether dental insurance influences how institutionalized older adults
      ages 65 and older rank their oral health status, a census survey was designed for
      residents of Durham's (Canada) Municipal Homes for the Aged. The odds ratio (OR)
      and the Cochran & Mantel-Haenszel's OR were used to estimate the crude and
      adjusted effect of dental insurance on oral health status, respectively. Overall,
      64 percent participated in the interview. Oral health status was ranked as
      "good," "very good" or "excellent" by 57 percent of the participants. This
      ranking was clearly unrelated to the residents having dental insurance, as only
      28 percent had dental coverage. Significant effect modifiers included age, dental
      status and whether the participant had visited the dentist within the last year.
      Dental insurance positively influenced how dentate participants ranked their oral
      health status (OR = 2.26; 95 percent CI = 1.19; 4.28). In edentulous
      participants, age and visiting the dentist within the last year modified the
      effect of dental insurance on oral health status. Having dental insurance reduced
      the odds of reporting "good," "very good" or "excellent" oral health (OR = 0.20;
      95 percent CI = 0.08; 0.49) among the participants ages 85 and older who did not
      visit the dentist within the last year; however, the opposite was true for their
      younger counterparts who visited the dentist within the last year (OR = 7.20; 95
      percent CI = 1.08; 47.96). In this population, therefore, dental insurance was
      associated with higher oral health status rank among the dentate, but its effect
      on the edentulous population depended on age and the pattern of visiting the
      dentist.

PMID- 16463601
TI  - The perceptions of homeless people in Stockholm concerning oral health and
      consequences of dental treatment: a qualitative study.
AB  - This study investigated the perceptions of Swedish homeless people concerning
      their oral health and perceived consequences of dental treatment. Candid, tape
      recorded interviews were conducted in a conversational style. A phenomenological
      hermeneutical method was used to analyze the subjects' stories. New participants
      were recruited into the study, until the interviews provided no additional new
      information, which occurred after eight interviews. All narratives revealed
      expressions of loss as well as recovery in the informants' life. Both aspects
      highlighted the fact that homelessness equated to "loss" not only of a permanent
      residence but also of many values. Similarly, oral health was described and
      interpreted in terms of loss and recovery. During periods of drug abuse, study
      participants ranked oral health as a low priority and generally received only
      emergency dental attention. In more rehabilitative phases of life, however, they
      perceived oral health and dental treatment as a function to restore their human
      dignity and as a key to their holistic recovery of total body health.

PMID- 16463602
TI  - Adaptations of mouthguards for patients with special needs.
AB  - The adaptations and applications of mouthguard appliances are many and varied,
      with uses ranging from protective to therapeutic. These modifications serve the
      individual needs of patients. This requires problem-solving based on combining
      form and function with the skills of the dentist.

PMID- 16463604
TI  - Contingency experiences of 3-month-old children and their relation to later
      developmental achievements.
AB  - In this study, the authors investigated the relation between early social
      contingency experiences and infants' competencies to detect nonsocial
      contingencies. In this study of 87 three-month-old infants, the authors
      operationalized early social contingencies as prompt, contingent maternal
      responses and coded microanalytically on the basis of video-recorded mother
      infant interactions. The authors assessed competence to detect nonsocial
      contingencies by 2 methods: (a) the mobile conjugate reinforcement paradigm,
      which focuses on detecting contingencies between the infants' actions (kicking)
      and nonsocial consequences (mobile moving) and (b) the visual expectation
      paradigm, which focuses on detecting contingencies between 1 event (a smiley face
      projected on a screen) that was followed by a 2nd event (a complex picture
      projected on the other side of the screen). The results showed that early social
      contingencies are related to the competency to detect nonsocial action
      consequence contingencies in the mobile conjugate reinforcement paradigm.

PMID- 16463603
TI  - A comparison of caries rates in non-institutionalized individuals with and
      without Down syndrome.
AB  - The caries rate of people with Down syndrome (DS) was compared to an age-matched
      control population without DS. A cross-sectional study design was used. Caries
      rates were assessed by an adjusted DFT score, expressed as a proportion of number
      of teeth in the mouth, to control for hypodontia in the subjects with DS.
      Bivariate and multiple linear regression analyses were used to compare caries
      rates in persons with and without DS. The sample size was 128, in which 44 were
      subjects with DS and 84 were subjects without DS. On a range of 0-1, the mean
      adjusted DFT scores were 0.10 in subjects with DS and 0.18 in the control group.
      Although this difference was significant at the bivariate level of analysis, in
      the multiple linear regression model, adjusted DFT was associated with age and
      professional fluoride therapy only. When expressed as a proportion of number of
      teeth, caries rates were not different in people with and without DS.

PMID- 16463605
TI  - Prenatal cocaine exposure and infants' preference for novelty and
      distractibility.
AB  - The authors used the Fagan Test of Infant Intelligence (J. F. Fagan, L. T.
      Singer, J. E. Montie, & P. A. Shepherd, 1986) to examine preferences for novelty
      and to evaluate several indicators of attention (off- and on-task indexes and
      durations) in 6- and 9-month-old infants who had been prenatally exposed to
      cigarette smoke only or to cocaine plus other substances. The infants were
      matched for socioeconomic status. The authors found no group differences in
      preference for novelty, but the off-task distractibility index and duration were
      affected by exposure history and showed effects of dosage at the 9-month test
      time. Infants exposed to cocaine had a higher off-task index and a shorter
      average off-task look duration than did infants in the other groups. The authors
      interpreted this pattern of behavior as an indicator of distractibility or
      stimulation seeking. There were no group differences in measures involving on
      task looks or duration at either test time. Correlations between the off-task
      look index and duration and teratogen use produced moderate correlations at 9
      months of age. The authors calculated partial correlations between teratogen
      exposure and the off-task index at each trimester. Cocaine use during the 1st and
      2nd trimesters was significantly correlated with the off-task index at 9 months
      of age, even when the authors controlled for neonatal measures (e.g., gestational
      age, birth weight) and during the 1st trimester when they controlled for alcohol
      and cigarette exposure.

PMID- 16463606
TI  - Reading experience and changes in the processing of letters, written words, and
      pseudohomophones: comparing fifth-grade students and university students.
AB  - In this study, the author elucidated whether reading experience continues to
      contribute to word recognition skills in readers with well-internalized reading
      skills. The participants performed consecutive same or different judgments
      regarding the identicalness of letters, words, and pseudohomophones. For a more
      detailed examination of how increased reading experience impacts particular
      stages of the processing of written stimuli, the author manipulated the identity
      dimension in each stimuli category. Twenty-five 5th-grade students and 22
      university students participated in the study. Overall, findings indicated that a
      significant development occurs in the recognition of written stimuli after 5th
      grade because of a shift in the strategic allocation of mental resources
      (attention) within the recognition process. This change in strategy seems to
      prompt enhanced retrieval of knowledge relevant to the processing of written
      stimuli.

PMID- 16463607
TI  - Memory failures appraisal in younger and older adults: role of individual
      difference and event outcome variables.
AB  - The authors examined the role of individual difference and event outcome
      variables in younger and older adults' memory failures appraisal. Participants
      read vignettes that described fictitious younger characters (in their 20s-30s) or
      older characters (in their 60s-70s) who had experienced a minor or severe
      consequence of their forgetfulness. The authors solicited attribution ratings on
      the potential causes of the forgetfulness and memory opinion ratings. Younger and
      older adults' ratings were largely similar, although age differences occurred on
      the effort and luck attribution scales. The consequences of the forgetting had a
      sizable impact on both the attribution and memory opinion ratings. Individual
      differences in self-reported memory had a relatively small impact on causal
      attribution and memory opinion ratings. These results suggested that people weigh
      their judgments of fictitious forgetful characters against event outcomes more so
      than ageist beliefs that portray a negative image of cognitive competence in
      later life.

PMID- 16463608
TI  - Cognitive processes in the reflective-impulsive cognitive style.
AB  - In this study, the authors improved the understanding of the cognitive processes
      underlying the reflective-impulsive cognitive style (RI), which was initially
      measured by J. Kagan, B. L. Rosman, D. Day, J. Albert, and W. Phillips (1964) on
      the Matching Familiar Figures Test (MFFT). The authors determined the
      relationships between the RI style and the cognitive factors, which would be
      likely to explain different MFFT solving modes-field dependence or independence
      as a cognitive style, the g factor, the spatial factor, and a metacognitive
      control index, which the authors developed for this study. The hypotheses were
      largely based on various studies (J. P. Ancillotti, 1984, 1985; J. Kagan, B. L.
      Rosman, D. Day, J. Albert, & W. Phillips, 1964; T. Zelniker & W. E. Jeffrey,
      1976; T. Zelniker, A. Renan, I. Sorer, & Y. Shavit, 1977). The results are
      presented separately for each of four groups: (a) reflective individuals, who
      implement an analytic process and are cognitively mature; (b) impulsive
      individuals, who use a holistic process and are cognitively immature; (c) fast
      accurate individuals, who are capable of implementing both analytic and holistic
      processes and exhibit cognitive maturity; and (d) slow-inaccurate individuals,
      who exhibit good metacognitive control but have trouble implementing both types
      of processing.

PMID- 16463610
TI  - [Severe pneumonia from psittacosis in a bird-keeper].
AB  - A 67-year-old man was admitted due to severe pneumonia. Initially he was treated
      with beta-lactam antibiotics and oxygen. However, he developed respiratory
      failure and was transferred to the intensive-care unit for mechanical
      ventilation. He was a bird-keeper who collected many species of exotic birds,
      including parrots. The diagnosis psittacosis (parrot fever) was confirmed
      serologically and by PCR on bronchoalveolar lavage fluid. PCR techniques lead to
      rapid diagnosis which allows for early treatment. The initial treatment of
      atypical pneumonia with ciprofloxacin failed. After the patient was treated with
      doxycycline 200 mg i.v. his clinical condition improved and he was cured. The
      patient was discharged from intensive care after 10 days when acute respiratory
      distress syndrome and pericarditis had resolved. Psittacosis is seen sporadically
      in the Netherlands. It may be encountered more frequently among patients who have
      had contact with birds and should be considered in the differential diagnosis of
      atypical pneumonia.

PMID- 16463609
TI  - Hemispheric cognitive style: a comparison of three instruments.
AB  - In this study, the author tested the reliability, concurrent validity, and
      predictive validity of three hemispheric cognitive style instruments: (a) the
      Preference Test (PT; R. Zenhausern, 1978), (b) the Polarity Questionnaire (PQ; B.
      E. Morton, 2002), and (c) the Wagner Preference Inventory II (WAPI II; R. F.
      Wagner & K. A. Wells, 1985). Participants were either teachers or teachers in
      training. The prediction criterion was in the area of teaching licensure. Scores
      on the PQ had extremely low reliability, and correlations with the PT and the
      WAPI II were not significantly different from zero. In addition, the PQ did not
      correlate with the licensure area. The author found that both the PT and the WAPI
      II had reasonable levels of reliability, and both instruments were able to
      explain a small percentage of the variance in the teaching licensure area. Using
      factor analysis of the PT, the author found a 7-factor structure, which suggests
      that hemispheric cognitive style might be decomposable into separate holist
      analytic and visual-verbal dimensions.

PMID- 16463611
TI  - [Insulin resistance: the role of intramuscular triglyceride and the importance of
      physical activity].
AB  - In the Netherlands, the prevalence of diabetes is expected to rise from 480,000
      to more than 650,000 patients by the year 2020. Numerous studies have reported a
      strong correlation between elevated plasma-free fatty-acid levels, the
      accumulation of intramuscular triglyceride (IMTG) and the development of insulin
      resistance. Traditionally, the Randle cycle was used to explain the mechanism
      behind fatty acid-induced insulin resistance in skeletal muscle. An alternative
      explanation is that the increased supply of free fatty acids leads to the
      accumulation of IMTG and fatty-acid metabolites, which can induce defects in the
      insulin signalling cascade, causing insulin resistance in skeletal muscle.
      However, this proposed relationship between elevated IMTG concentrations and
      skeletal-muscle insulin resistance does not always apply, as trained athletes
      have been shown to be markedly insulin-sensitive, despite having high levels of
      stored IMTG. This metabolic paradox is explained by the fact that it is not the
      size of the IMTG pool but rather the balance between fatty-acid availability,
      uptake and oxidation, i.e. the low turnover of the IMTG pool, that is
      instrumental in the development of skeletal-muscle insulin resistance. Physical
      exercise forms an effective strategy to improve the balance between skeletal
      muscle fatty-acid uptake and oxidation and, as such, can prevent the development
      of skeletal-muscle insulin resistance.

PMID- 16463612
TI  - [The mechanism of action of cannabis and cannabinoids].
AB  - The effect ofcannabis can be explained on the basis of the function of the
      cannabinoid receptor system, which consists of CB receptors (CB1, CB2),
      endoligands to activate these receptors and an enzyme--fatty acid amidohydrolase-
      to metabolize the endoligands. The endoligands of the cannabinoid receptor system
      are arachidonic acid-like substances, and are called endocannabinoids.
      Indications exist that the body also contains arachidonic acid-like substances
      that inhibit fatty acid amido hydrolase. Various cannabinoids have diverse
      effects on the receptors, functioning as agonists, antagonists or partial
      antagonists, as well as affecting the vanilloid receptor. Many known effects
      ofcannabis can be explained on the basis of this mechanism of action as can the
      use ofcannabis in various conditions including multiple sclerosis, Parkinson's
      disease, glaucoma, nausea, vomiting and rheumatoid arthritis.

PMID- 16463613
TI  - [Teriparatide: an anabolic drug for the treatment of patients with osteoporosis].
AB  - The management of osteoporosis has been dominated by the use of antiresorptive
      agents, such as bisphosphonates and raloxifene, which have been shown to
      effectively reduce the risk of osteoporotic fractures. Teriparatide, a
      recombinant human parathyroid hormone, has recently become available. It has an
      altogether different action. Teriparatide is an anabolic agent that primarily
      stimulates bone formation. This leads to an increase in bone volume and the bone
      structure and microarchitecture is restored by an increase in trabecular
      thickness and an increase in the number of connections between trabeculae.
      Clinically relevant studies on teriparatide in postmenopausal women and in men
      have shown that it significantly lowers the risk of fracture. Teriparatide should
      not be combined with bisphosphonates. There are no clear recommendations on the
      order of treatment with teriparatide and bisphosphonates. The high costs
      ofteriparatide have slowed the trajectory from registration to reimbursement in
      the Netherlands. Since 1 February 2005 teriparatide may be prescribed for
      postmenopausal women with serious osteoporosis i.e. with a minimum of 1
      osteoporotic fracture who (a) despite treatment with bisphosphonates or
      raloxifene after 2 prolapsed vertebrae once again have 1 or more fractures
      (inadequate response); (b) can tolerate neither bisphosphonates nor raloxifene;
      (c) are prescribed the drug by their treating medical specialist.

PMID- 16463614
TI  - [In favour of laparoscopic versus open prostatectomy].
AB  - The introduction of a new technique typically generates concern regarding the
      associated time, costs and efforts. The favourable functional results of the
      laparoscopic approach to prostate cancer must be weighed against the potential
      disadvantages of this approach. The short-term oncologic results justify further
      implementation of the laparoscopic technique.

PMID- 16463615
TI  - [In favour of open versus laparoscopic prostatectomy].
AB  - Recovery following uncomplicated laparoscopic radical prostatectomy is somewhat
      faster than that following open prostatectomy. Recovery of erectile function also
      occurs faster and better. However, these advantages are gained at the cost of
      more positive resection fields and less favourable oncologic results.
      Postoperatively, many patients appear to have T3 tumours, which cannot be
      optimally detected with current imaging techniques. Therefore, an open operation
      remains preferable.

PMID- 16463616
TI  - [From the Cochrane Library: Improvement of photodamaged skin with retinoid creams
      and not with other local treatments].
AB  - A Cochrane systematic review of 30 randomised clinical trials assessed the
      effects of current treatments for adults with mild-to-severe changes in facial
      and forearm skin that occurred as a result of prolonged exposure to the sun
      ('photodamage'). Topical tretinoin > or = 0.02% improved the appearance of mild
      to-severe photodamage. Tazarotene 0.01-0.1% and isotretinoin 0.1% provided
      benefit to patients with moderate photodamage. The treatment duration was 4-11
      months. Adverse effects were pain and redness. Both the efficacy and adverse
      effects were dose-dependent. Other treatments, such as polysaccharides, hydroxy
      acids, surgical procedures and laser, cannot be recommended.

PMID- 16463617
TI  - [Diagnosis image (258). A women with a 'bullet' in the abdomen].
AB  - A 48-year-old woman had 17 years after hysterosalpingography a collection of
      contrast fluid, suggesting a bullet, in the abdomen.

PMID- 16463618
TI  - [Oesophageal endoscopic ultrasound with fine-needle aspiration biopsy in the
      staging of non-small-cell lung carcinoma; results from 43 patients].
AB  - OBJECTIVE: To calculate the number of cervical mediastinoscopies that need not be
      carried out ifoesophageal endoscopic ultrasound and fine-needle aspiration biopsy
      (EUS-FNA) are included in the staging of patients with non-small-cell lung
      carcinoma (NSCLC). DESIGN: Retrospective, descriptive. METHOD: Patients referred
      to the St. Antonius Hospital in Nieuwegein, the Netherlands, with NSCLC from
      January to December 2003 routinely underwent EUS-FNA during the staging process.
      If mediastinal or distant metastases were found to be present then cervical
      mediastinoscopy was not carried out as the patient was not eligible for
      operation. If no metastases were demonstrated then cervical mediastinoscopy was
      carried out. The value of EUS-FNA was calculated. RESULTS: A total of 43 patients
      underwent EUS-FNA: 32 men and 11 women with an average age of 64 (range: 45-77).
      In 22 (51%) of them, cervical mediastinoscopy was not performed as EUS-FNA
      demonstrated malignant cells in the lymph nodes of the mediastinum or abdomen, in
      the left adrenal gland or in the primary tumour which had grown into the
      mediastinum. In 2 of the 21 other patients malignant cells were found on
      mediastinoscopy showing the EUS-FNA results in 2 of 43 patients (5%) to be false
      negative. No complications occurred. CONCLUSION: Based on the findings from EUS
      FNA, cervical mediastinoscopy was not performed in 51% of the patient group.

PMID- 16463620
TI  - [Western psychiatric literature in Eastern Europe: the publication programme of
      the Global Initiative on Psychiatry].
AB  - Global Initiative on Psychiatry (GIP) foundation was set up in 1980 as a reaction
      to the misuse of psychiatry for political purposes. After the revolutions in
      Eastern Europe, GIP devoted itself to the reform of the mental healthcare in
      Central and Eastern Europe and the former Soviet Union. Here, GIP makes a special
      effort to eliminate the arrears in comparison with world psychiatry. More than
      30,000 books and journals have been collected internationally and delivered to
      Eastern Europe from the Netherlands in convoys with relief supplies. These gifts
      still represent the heart of the extensive library of the Ukrainian Psychiatric
      Society. Via a translation and publication programme in Russian and later also in
      other languages (Ukrainian, Bulgarian, Romanian, Albanian, Estonian, Lithuanian,
      Armenian, Georgian and Azerbaijani), handbooks such as the International
      Classification of Diseases of the WHO (ICD-10) and other standard works have been
      published. In addition, since 1998 a unique journal has been published: the
      Review of Contemporary Psychiatry, a journal for psychiatrists and other
      professionals in which a selection of the most interesting articles in the
      Western psychiatric literature is offered in Russian translation, without
      advertising from the pharmaceutical industry.

PMID- 16463619
TI  - [Gout as an unusual cause of pelvic pain].
AB  - An 89-year-old woman was admitted for high fever and debilitating pelvic pain,
      notably in the pubic area. Physical examination revealed multiple gouty tophi in
      her hands and feet. Laboratory investigation revealed severe leukocytosis and a
      sharply increased C-reactive protein level. The patient was treated with broad
      spectrum antibiotics in view of the possibility of a serious bacterial infection,
      but there was no clinical effect. CT of the pelvis revealed an osteolytic process
      and a mass anterior to the pubic symphysis. Histological investigation of a
      biopsy revealed an inflammatory infiltrate with signs of gout. Culture of the
      biopsy specimen was negative. The diagnosis was confirmed by the finding ofneedle
      like urate crystals under the polarizing microscope. After treatment with
      colchicine and later with prednisone, the symptoms disappeared. She was given
      uric acid-lowering therapy with allopurinol as a preventive measure.

PMID- 16463621
TI  - [The clinical relationship between symptoms and the final diagnosis in general
      practice, determined by means of posterior probabilities calculated on the basis
      of the Transition Project].

PMID- 16463622
TI  - [Three women with autoimmune hepatitis: the clinical importance of early
      diagnosis and remission].

PMID- 16463623
TI  - [Towards a national programme for prenatal screening for Down's syndrome].

PMID- 16463624
TI  - [The role of post-graduate course in making the department of medical service
      organization and tactics in Military Medical Academy up to strength].

PMID- 16463625
TI  - [Organization of support and quality control of medicaments in Russian Federation
      Armed Forces medical service].
AB  - The article presents the chronological analysis of formation of the system for
      providing the medicament quality control in the medical service of Russian
      Federation Armed Forces. The role of Centers of medicament quality control and
      certification in the State system for providing medicament quality is
      demonstrated. The aims of these Centers are to prevent the getting of poor and
      falsified medicaments into the troops. The practical work of the Centers during 4
      years was analyzed. As the result 35 types of falsified and 97 types of poor
      medicaments were revealed. The proposals for improving medicament quality control
      in the medical service of RF Armed Forces are given.

PMID- 16463626
TI  - [Purulent diseases of hand fingers in servicemen of Pribaikalye].

PMID- 16463627
TI  - [Changes in immune status after myocardial revascularization with the use of two
      methods of artificial circulation].

PMID- 16463628
TI  - [The possibility of individual identification by revealing the somatic diseases
      manifested during lifetime basing on the results of bone tissue element
      analysis].

PMID- 16463630
TI  - [Influence of exogenous hyperthermia trainings on the state of body unspecific
      resistance].

PMID- 16463629
TI  - [Community pneumonia in recruits: the algorithm of complex two-staged
      rehabilitation treatment].
AB  - The program of complex recovery therapy and medical rehabilitation (MR) for
      treating the patients with mild form of community-acquired pneumonia (CAP) is
      presented. 89 servicemen-recruits with CAP mild form treated during 2003-2005 in
      the Field Therapy Clinic of Saratov Military Medical Institute were investigated.
      MR was conducted on the basis of medical station (MS) and lasted for 15 days.
      Physiological, laboratory and instrumental parameters were evaluated at the day
      of antibiotic therapy cancel, on discharge from hospital, on the 5-th and 15-th
      day of MR. The peroxidation activity, intensity of unspecific resistance
      mechanisms and obstructive impairment of bronchial passages remained during CAP
      late phases. Only on the 15th day of extensive medical rehabilitation measures in
      80,7% of those suffered from CAP the reserve capacity indices of cardiovascular
      system reached the lower level of the border state of PWC170 test scales,
      Skibinskiy's and Bogomazov's tests. The proposed two-staged program of medical
      rehabilitation in CP cases which includes the combined use of actoprotector and
      antioxidant, restoration of bronchial tree drainage function, early introduction
      of breathing exercises and cyclotraining allowed achieving the restoration of
      working and fighting capacity in short terms. The stay in pulmonologic in-patient
      department became 3 days less.

PMID- 16463631
TI  - [Clinical-and-neurological characteristic and expert evaluation of dorsopathy in
      flying staff].

PMID- 16463633
TI  - Something to celebrate at the best of times and the worst of times.

PMID- 16463632
TI  - [About the history of creation and development of the system for rendering
      skilled surgical care in the troop region].
AB  - Practice of rendering the elements of skilled surgical care to the wounded in
      Russian Army during the wars of first half of the XIX century has coincided with
      introduction of evacuation system into medical support of troops' military
      operations. With improvement of the last. advantages of medical-and-biologic
      science, military skills the battery sick quarters, dressing detachments
      providing the work of main dressing stations, the medical care main stations were
      subsequently included into the kit of medical service means of the formations. In
      December 1935 this process was ended with creation of division medical-and
      sanitary battalion (deployed by the division medical station) that took an active
      part in rendering skilled surgical care to the wounded during the subsequent
      local military conflicts and wars.

PMID- 16463637
TI  - Wait times.

PMID- 16463638
TI  - RNAO: speaking out for health, speaking out for nursing.

PMID- 16463639
TI  - A sabbatical journey of discovery: the liberation of nursing.

PMID- 16463640
TI  - Shirlee Sharkey: extraordinary things are possible.

PMID- 16463641
TI  - Annual report: September 2004 to November 2005.

PMID- 16463642
TI  - Waiting lists and nursing.

PMID- 16463643
TI  - The promise of the health sciences in the 21st century.

PMID- 16463644
TI  - New health professionals network: the future face of medicine.

PMID- 16463645
TI  - Case study: nursing professional practice councils: the quest for nursing
      excellence.
AB  - The quest for nursing excellence requires enthusiasm, commitment and a dedicated
      team of nurses. The desire to create an environment where nurses were valued,
      supported and empowered led to the development of a Nursing Professional Practice
      Council within an Ontario Public Health Unit. The journey is described in detail,
      from planning and implementation through lessons learned and recommendations for
      organizations embarking on a similar quest. As a direct result of the Nursing
      Professional Practice Council, experiences within the organization have exceeded
      expectations, justified the financial costs and improved relationships among all
      parties.

PMID- 16463646
TI  - Registered nurse and registered practical nurse evaluations of their hospital
      practice environments and their responses to these environments.
AB  - In 2003, over 13,000 Ontario nurses were surveyed to explore how they evaluated
      their hospital work environments and their responses to these practice
      environments. The purpose of this paper is to describe and compare these nurses'
      evaluations and responses. Sixty-five percent of nurses who were mailed surveys
      completed and returned a survey. Significant differences were found between
      registered nurse and registered practical nurse characteristics such as mean age,
      full-time employment rates, mean years of nursing experience and proportion
      enrolled in university or college educational programs. Both groups reported weak
      professional practice environments; however, there were some significant
      differences between the evaluations by registered nurses and those of registered
      practical nurses. Although both groups reported weak job satisfaction and
      moderate levels of burnout, there were significan differences in other responses.
      Study findings have implications for managing and leading nurses and for
      strengthening human resources practices.

PMID- 16463647
TI  - Illuminating the clinical nurse specialist role of advanced practice nursing: a
      qualitative study.
AB  - As the advanced practice nursing initiative in Canada gains momentum, effort is
      being directed towards clarifying and defining advanced practice roles. A
      qualitative study was undertaken to increase understanding of the clinical nurse
      specialist role of advanced practice. Sixteen nurses who worked in advanced
      practice roles, organizing and providing healthcare for children with complex
      health needs and their families across the continuum of care, participated in in
      depth conversations about the nature of their practice, the knowledge that
      informs it and the factors that influence it. Findings suggest that clinical
      nurse specialists have a unique role in the organization and delivery of
      healthcare for specialized populations with complex health needs in their dual
      focus on the system level of healthcare and on population health needs.
      Initiatives directed to children and families within the study participants'
      specialties included program development, consultation and educational outreach
      and the development of clinical guidelines and policies. Although the nurses
      described their practice as focusing both on individual children and families and
      on the population of children and families within their specialty, it is at the
      population level that they see their greatest potential for contributing to the
      delivery of high-quality, cost-effective healthcare.

PMID- 16463648
TI  - Screening of TACE peptide inhibitors from phage display peptide library.
AB  - To obtain the recombinant tumor necrosis factor-alpha converting enzyme (TACE)
      ectodomain and use it as a selective molecule for the screening of TACE peptide
      inhibitors, the cDNA coding catalytic domain (T800) and full-length ectodomain
      (T1300) of TACE were amplified by RT-PCR, and the expression plasmids were
      constructed by inserting T800 and T1300 into plasmid pET-28a and pET-28c
      respectively. The recombinant T800 and T1300 were induced by IPTG, and SDS-PAGE
      and Western blotting analysis results revealed that T800 and T1300 were highly
      expressed in the form of inclusion body. After Ni(2+)-NTA resin affinity
      chromatography, the recombinant proteins were used in the screening of TACE
      binding peptides from phage display peptide library respectively. After 4 rounds
      of biopanning, the positive phage clones were analyzed by ELISA, competitive
      inhibition assay and DNA sequencing. A common amino acid sequence
      (TRWLVYFSRPYLVAT) was found and synthesized. The synthetic peptide could inhibit
      the TNF-alpha release from LPS-stimulated human peripheral blood mononuclear
      cells (PBMC) up to 60.3%. FACS analysis revealed that the peptide mediated the
      accumulation of TNF-alpha on the cell surface. These results demonstrate that the
      TACE-binding peptide is an effective antagonist of TACE.

PMID- 16463649
TI  - Mechanisms of increased expression of toll-like receptor-4 in human
      monocyte/macrophage-derived foam cells.
AB  - The mechanisms of increased expression of toll-like receptor 4 (TLR-4) during the
      formation of foam cells were explored. Low density lipoprotein (LDL) was prepared
      by density gradient ultracentrifugation and oxidized by incubation with CuCl2.
      The human monocytic leukemia cell line (THP-1) was cultured in RPMI1640. The
      differentiation of THP-1 cells into macrophages (MPs) was induced by using
      myristate acetate (PMA) for 48 h. The macrophages were then incubated with
      oxidized LDL (ox-LDL) to generate foam cells (FCs). The mRNA and protein
      expression levels of human TLR-4 were detected by immunocytochemistry, Western
      blotting and reverse transcription polymerase chain reaction (RT-PCR). The
      results showed that the TLR-4 mRNA and the protein expression levels were
      significantly increased during the differentiation of monocytes into macrophages
      (P < 0.05) as well as during the formation of lipid-laden foam cells (P < 0.05).
      It was concluded that the upregulation of human TLR-4 gene expression during the
      differentiation of monocytes into macrophages and the differentiation of
      macrophages into foam cells could increase TLR-4 protein synthesis dramatically,
      which may enhance the ability of foam cells inflammation reaction in
      atherosclerosis.

PMID- 16463650
TI  - Effects of human cytomegalovirus infection on apoptosis and expression of
      apoptosis-regulating factors.
AB  - The present study aimed to find out dynamic changes of apoptosis in human
      cytomegalovirus (HCMV) infected cells and the influence of HCMV infection on
      activation of caspase-3 and the expression of apoptosis-regulating genes, bcl-2
      and fas mRNA. The sequential changes of apoptotic cell rate in high and low MOI
      (MOI = 2.5 and 0.25 respectively) of HCMV infected human embryonic lung
      fibroblasts (HELFs) at 1 h, 12 h, 24 h, 36 h, 48 h, 72 h and 96 h post-infection
      were measured by flow cytometry. The expression levels of caspase-3 protein and
      bcl-2 and fas mRNA in HCMV infected cells (MOI = 0.25) at 72 h post-infection
      were detected by Western blot and in situ hybridization methods, respectively. It
      was found that the ratio of apoptotic cells in normal controls was consistently
      lower, but the rates in low and high MOI infected cells were gradually increased
      with time prolonged, reached peak at 96 h (8.85%) and 72 h (25.63%),
      respectively. By Western blot analysis, only a narrow band of 32 kD (1 kD = 0.992
      1 ku) procaspase-3 was found in normal cells, but a wider procaspase-3 band and a
      much wider band of 17 kD proteins (p17) appeared in the infected cells.
      Meanwhile, the expression of bcl-2 mRNA was higher and that of fas mRNA was lower
      in the normal HELF cells, whereas there were significantly lower bcl-2 mRNA and
      higher fas mRNA expression levels in HCMV infected cells. It was concluded that
      HCMV was a stronger inducer of apoptosis in HELF cells. Caspase-3, as the marker
      of undergoing apoptosis, was expressed increasingly and activated in the infected
      cells, indicating its action in HCMV-inducing apoptosis. Down-regulating bcl-2
      mRNA expression and up-regulating fas mRNA expression were also involved in the
      mechanism of HCMV-induced apoptosis.

PMID- 16463651
TI  - Regulation of astroglia on synaptic plasticity in the CA1 region of rat
      hippocampus.
AB  - The regulation of astroglia on synaptic plasticity in the CA1 region of rat
      hippocampus was examined. Rats were divided into three groups: the newly born (<
      24 h), the juvenile (28-30 days) and the adult groups (90 - 100 days), with each
      group having 20 animals. The CA1 region of rat hippocampus was
      immunohistochemically and electron-microscopically examined, respectively, for
      the growth of astroglia and the ultrastructure of synapses. The high performance
      liquid chromatography was employed to determine the cholesterol content of rat
      hippocampus. In the newly-born rats, a large number of neurons were noted in the
      hippocampal CA1 region of the newly-born rats, and few astroglia and no synaptic
      structure were observed. In the juvenile group, a few astroglias and some
      immature synapses were found, which were less than those in adult rats (P <
      0.01). The cholesterol content was 2.92 +/- 0.03 mg/g, 11.20 +/- 3.41 mg/g and
      12.91 +/- 1.25 mg/g for newly born, the juvenile and the adult groups,
      respectively, with the differences among them being statistically significant (P
      < 0.01). Our study suggests that the astrocytes may play an important role in the
      synaptic formation and functional maturity of hippocampal neurons, which may be
      related to the secretion of cholesterol from astrocytes.

PMID- 16463652
TI  - Differentiation of bone marrow mesenchymal cells to neural cells.
AB  - To explore the possibility and condition of differentiation of bone marrow
      mesenchymal cells (BMSCs) to neural cells in vitro, BMSCs from whole bone marrow
      of rats were cultured. The BMSCs of passage 3 were identified with
      immunocytochemical staining of CD44 (+), CD71 (+) and CD45 (-). There were type I
      and type II cells in BMSCs. Type I BMSCs were spindle-shaped and strong positive
      in immunocytochemical staining of CD44 and CD71, whereas flat and big type II
      BMSCs were lightly stained. The BMSCs of same passage were induced to
      differentiate into neural cells by beta-mercaptoethanol (BME). After induction by
      BME, the type I BMSCs withdrew to form neuron-like round soma and axon-like and
      dendrite-like processes, and were stained positively for neurofilament (NF). The
      type II BMSCs did not change in the BME medium and were negatively or slightly
      stained of NF.

PMID- 16463653
TI  - Hypoglycemic activity of jatrorrhizine.
AB  - The hypoglycemic activity and its mechanism of Jatrorrhizine (Jat) were studied.
      The normal mice and alloxan-induced hyperglycemic mice were given with different
      doses of Jat. Blood glucose and liver glycogen levels were determined by
      spectrophotometry with glucose-oxidase and iodine reagents respectively. The
      levels of blood lactic acid (LC) and liver lactate dehydrogenase (LDH) activity
      were measured to explore the effect of Jat on anaerobic glycolysis. Succinate
      dehydrogenase (SDH) activity in liver was measured to evaluate the effect of Jat
      on aerobic glycolysis in liver. It was found that Jat (50 mg/kg, 100 mg/kg) could
      significantly decrease blood glucose level in a dose- and time-dependent manner
      in both normal and alloxan-diabetic mice, increase the activity of SDH, but had
      no significant effects on the LC level and LDH activity. Jat could significantly
      reduce the content of liver glycogen in normal mice. Moreover, Jat could inhibit
      the platelet aggregation in rabbits in vitro in a dose-effect relationship. It
      was concluded that Jat induced the pronounced decrease in blood glucose in normal
      and hyperglycemic mice. The hypoglycemic activity of Jat may be attributed to the
      enhancement of aerobic glycolysis.

PMID- 16463654
TI  - Correlation between pulmonary endothelin receptors and alveolar-arterial oxygen
      gradient in rats with hepatopulmonary syndrome.
AB  - The correlation between pulmonary endothelin receptors and alveolar-arterial
      oxygen gradient (A-aDO2) in rats with hepatopulmonary syndrome was investigated.
      Animals were divided into 2 groups: Sham-operated (Sham) group and common bile
      duct ligation (CBDL) group. Arterial blood gas was evaluated by a blood gas
      analyzer. The concentrations of ET-1 in blood and lung tissue sample were
      evaluated by radioimmunoassay. The distribution and expression of two kinds of
      subtype receptor of ET-1, ETRA and ETRB were examined by in situ hybridization.
      The results showed that the level of A-aDO2 was higher in CBDL group than that in
      Sham group (P < 0.05). The levels of plasma and pulmonary ET-1 in CBDL group were
      both higher than in Sham group (P < 0.05). There was no significant difference in
      average A of ETRA between two groups by imaging analysis (0.21 +/- 0.06 vs 0.22
      +/- 0.08, P > 0.05), while that of ETRB was higher in CBDL group than in Sham
      group (0.58 +/- 0.16 vs 0.28 +/- 0.07, P < 0.05). The expression of ETRB in lung
      was positively correlated with A-aDO2 (P < 0.05). It was concluded that the
      widened A-aDO2 may be related with enhancement of the expression of ETRB in lung.

PMID- 16463655
TI  - Changes of monophasic action potential duration and effective refractory period
      of three layers myocardium of canine during acute ischemia in vivo.
AB  - The effect of acute ischemia on the electrophysiological characteristics of the
      three layers myocardium of canine in vivo was investigated. Twelve canines were
      divided into two groups randomly: acute ischemia (AI) group and sham operation
      (SO) group. By using the monophasic action potential (MAP) technique, MAP and
      effective refractory period (ERP) of the three layers myocardium were measured by
      specially designed plunge needle electrodes and the transmural dispersion of
      repolarization (TDR) and transmural dispersion of ERP (TDE) were analyzed. The
      results showed that in the AI group, MAP duration (MAPD) was shortened from
      201.67 +/- 21.42 ms to 169.50 +/- 13.81 ms (P < 0.05), but ERP prolonged to
      varying degrees and TDE increased during ischemia. In the SO group, MAPD and ERP
      did not change almost. Among of the three layers myocardium of canine, MAPD was
      coincident in two groups. It was concluded that during acute ischemia, MAPD was
      shortened sharply, but there was no significant difference among of the three
      layers myocardium. The prolonged ERP was concomitant with increased TDE during
      acute ischemia, which may play an important role in the occurrence of arrhythmias
      induced by acute ischemia. These findings may have important implications in
      arrhythmogenesis.

PMID- 16463656
TI  - Effect of L-carnitine on cardiomyocyte apoptosis and cardiac function in patients
      undergoing heart valve replacement operation.
AB  - The effects of L-carnitine, as an ingredient of cardioplegia solution, on cardiac
      function and cardiomyocyte apoptosis in patients undergoing heart valve
      replacement operation were investigated. Twenty-three cases undergoing heart
      valve replacement with cardiopulmonary bypass (CPB) were randomly allocated into
      two groups: L-carnitine group (n = 12, 12 g/L L-carnitine was put in the ST.
      Thomas cardioplegia) and control group (n = 11, identical to the L-carnitine
      group except that normal saline was administered instead of L-carnitine). Serum
      cardial troponin I (cTnI) levels, the left ventricular ejection fraction (LVEF),
      and cardiac index (CI) were measured perioperatively. A bit of myocardial tissue
      obtained from right atria was taken before CPB and by the end of intracardiac
      procedure to undergo electron microscopy examination and estimate apoptosis by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL).
      From the end of CPB to 3 days after operation, the serum levels of cTnI in the L
      carnitine group was significantly lower than that in the control group (P <
      0.05). Heart color ultrasonogram showed that the CI index and LVEF at 7th day
      postoperatively in the L-carnitine group were significantly higher than in the
      control group (P < 0.05). Compared to the control group, L-carnitine
      significantly alleviated the morphologic changes of cardiac muscle cells
      (electron microscopy examination) and decreased the amounts of apoptotic cardiac
      muscle cells (TUNEL). Furthermore, the dosage of vasoactive drugs used after
      operation was significantly less in the L-carnitine group (P < 0.01). It was
      concluded that L-carnitine cardioplegia solution could improve cardiac function
      in patients undergoing heart valve replacement operation and alleviate CPB
      mediated apoptosis of cardiac muscle cells.

PMID- 16463658
TI  - Expression of CD28 and CTLA4 on T cells in bone morrow of immune-mediated
      aplastic anemia mice.
AB  - To investigate the expression and significance of CD28 and CTLA4 on T cells in
      bone marrow of aplastic anemia (AA) mice, in vitro bone marrow mononuclear cells
      (BMMNCs) were activated through being incubated with PHA (15 microg/mL). The
      expression of CD28 and CTLA4 on T cells incubated with or without PHA was
      detected by two-color flow cytometry. The expression of CD28 and CTLA4 was
      significantly increased after PHA stimulation. In the AA mice, the expression of
      CD28 with or without PHA stimulation was both higher than that in the normal mice
      (both P < 0.01), but the expression of CTLA4 with or without PHA stimulation
      showed no significant difference in comparison to that in the normal mice (both P
      > 0.05). In the AA mice, there were more activation and activated potential of T
      cells than the normal, and the abnormal expression of CD28 and CTLA4 may
      participate in immunological disorder mediated by T cells.

PMID- 16463657
TI  - Construction of eukaryotic expression vector of human CC10 gene and expression of
      CC10 protein in lung adenocarcinoma A549 cell line.
AB  - A mammalian expression plasmid pcDNA3. 1-hCC10 was constructed and identified,
      then CC10 protein expression in A549 lung cancer cell line was detected. A 273 bp
      cDNA fragment was amplified from the total RNA of normal lung tissue by using RT
      PCR and cloned into expression plasmid cDNA3. 1, and the recombinant plasmid was
      identified by employing double digestion restriction enzymes Hind III and BamH I
      and the cDNA sequence was assayed by the Sanger dideoxy-mediated chain
      termination method. The segment was then transfected into the A549 lung cancer
      cell line. The protein expression of CC10 was detected by immunofluorescence and
      Western blot. Our results showed that the cDNA fragment included the entire
      coding region (273 bp). The recombinant eukaryotic cell expression vector of
      pcDNA3. 1-hCC10 was successfully constructed, and the sequence of the insert was
      identical to the published sequence. A549 cells line transfected with the pcDNA3.
      1-hCC10 expressed high level of CC10 protein. The recombinant plasmid cDNA3. 1
      hCC10 may serve as an effective tool for the study of tumorogenesis and tumor
      treatment.

PMID- 16463659
TI  - Enhancing effects of ligustrazine on expression of CD31 and hematopoietic
      reconstitution in syngenic bone marrow transplantation of mice.
AB  - The effect of ligustrazine on the expression of CD31 in syngenic bone marrow
      transplantation (BMT) mice was studied. Fifty-six Balb/c mice were divided into 3
      groups: normal control group, BMT control group, and ligustrazine treated group.
      Syngenic BMT mouse models were established according to the literatures. In BMT
      control group and the ligustrazine treated group, the mice were given
      respectively orally 0.2 mL saline and 2 mg ligustrazine twice a day. On the 7th,
      14th, and 21st day after BMT, the mice were killed. The expression of CD31 on the
      surface of bone marrow nuclear cells (BMNC) was detected by flow cytometry.
      Peripheral blood leukocytes, platelets and BMNC were counted. Histological
      observation of bone marrow was made. The results showed that in ligustrazine
      treated group the peripheral blood leukocytes. platelets and BMNC counts, and the
      expression of CD31 on the day 7, 14, 21 after BMT were higher than in BMT control
      group (P < 0.01 or P < 0.05). In conclusion, ligustrazine could obviously enhance
      the CD31 expression on the surface of BMNC after syngenic BMT in mice, which may
      be one of the mechanisms underlying the ligustrazine accelerating hematopoietic
      reconstitution in syngenic BMT.

PMID- 16463660
TI  - Apoptotic sensitivity to irradiation increased after transfection of chk1
      antisense chain to HL-60 cell line.
AB  - The HL-60 cells were transfected with chk1 antisense and sense chain, and 24 h
      later subjected to irradiation. Twenty-four h after irradiation, the changes in
      the chk1 protein expression was assayed by Western blot, and the cell cycles and
      apoptosis rate detected by FCM. The irradiated apoptosis sensitivity was
      increased by antisense blocking of chk1 gene in HL-60 cell line with the
      apoptosis rate being 26.31%, significantly higher than that by the sense blocking
      (10.34%, 0.025 < P < 0.05). In HL-60 cells transfected with chk1 antisense chain,
      the G2/M phase arrest was attenuated and the cells in G2/M phase were accounted
      for 38.42%, significantly lower than those of the cells transfected with chkl
      sense chain (54.64%, 0.005 < P < 0.01). It was concluded that antisense blocking
      of chk1 gene could increase the apoptosis sensitivity to irradiation.

PMID- 16463661
TI  - Effect of lipo-prostaglandin E1 on mesangial proliferative glomerulonephritis in
      rats.
AB  - The antinephritic effect of lipo-prostaglandin E1 prostaglandin E1 incorporated
      in lipid microspheres was investigated using an experimental model of mesangial
      proliferative glomerulonephritis (MsPGN). Twenty-two female rats were randomly
      divided into nephritic group (N, n = 6), lipo-prostaglandin E1 treated group (NL,
      n = 8) and control group (C, n = 6). Lipo-prostaglandin E1 was given
      intravenously at 40 microg x kg(-1) x d(-1) from the 6th week to the 8th week.
      Twenty-four h urinary protein contents and blood creatinine (Cr) were determined
      and the pathological changes were observed in the experiment. The expression of
      proliferating cell nuclear antigen (PCNA), extracellular matrix (fibronectin, FN;
      collagen type IV, Col IV) and transforming growth factor beta1 (TGFbeta1) was
      detected by using immunohistochemistry. The results showed that lipo
      prostaglandin E1 significantly inhibited the glomerular histopathological changes
      as well as the elevation of plasma Cr (P < 0.05). The overexpression of PCNA, FN,
      Col IV and TGFbeta1 were also obviously inhibited in group NL as compared with
      the group N (P < 0.01). It was suggested that lipo-prostaglandin E1 could improve
      renal function, inhibit the proliferation of glomerular cells and reduce the
      deposition of extracellular matrix, which may be related to the down-regulation
      of the TGFbeta1 expression.

PMID- 16463662
TI  - Expression of connective tissue growth factor in renal tubulointerstitial
      fibrosis in rats and its pathogenic role.
AB  - In order to explore the role of connective tissue growth factor (CTGF) in the
      pathogenesis of renal tubulointerstitial fibrosis, 48 Wistar rats were randomly
      divided into sham-operated and unilateral ureteral obstruction (UUO) group. On
      the postoperative day 1, 3, 7 and 14, the rats were killed and the kidneys were
      removed. The renal tubulointerstitial injury index was evaluated according to the
      MASSON staining. The mRNA levels of CTGF, transforming growth factor-beta1 (TGF
      beta1), collagen I (col I), and plasminogen activator inhibitor-1 (PAI-1) were
      detected using reverse transcriptional-polymerase chain reaction (RT-PCR).
      Immunohistochemistry was performed to evaluate the protein expression of the
      above factors, and the relations among them were analyzed. Quantitative
      expression of CTGF protein in the kidneys was also assessed using Western blot.
      The results showed that TGF-beta1 mRNA level was increased at first day after
      UUO, followed by a marked elevation of CTGF mRNA level, which began to increase 3
      days after UUO (P < 0.01). With the progression of the disease, the mRNA
      expression of CTGF, col I and PAI-1 was increased progressively.
      Immunohistochemistry revealed that the CTGF protein expression was significantly
      increased in fibrotic areas and tubular epithelial cells 3 days after UUO. On the
      post-UUO day 7, the protein level of CTGF was positively related to the renal
      tubulointerstitial injury index (r = 0.62, P < 0.01), the expression of TGF-beta1
      (r = 0.85, P < 0.01), col I (r = 0.78, P < 0.01), and PAI-1 (r = 0.76, P < 0.01).
      Upon Western blot analysis, CTGF protein expression began to increase 3 days
      after UUO, and appeared progressively throughout the time course (P < 0.01, as
      compared with sham-operated group). It is concluded that CTGF can be induced by
      TGF-beta and mediate various profibrotic actions of this cytokine, such as
      increasing extracellular matrix (ECM) synthesis and decreasing ECM degradation.
      The increased expression of CTGF may play a crucial role in the development and
      progression of tubulointerstitial fibrosis.

PMID- 16463663
TI  - Role of protease activated receptor-2 expression in renal interstitial fibrosis
      model in mice.
AB  - The role of protease activated receptor-2 (PAR-2) in the renal tubulointerstitial
      lesion induced by unilateral ureteral obstruction (UUO) was explored. Mice were
      sacrificed on the day 1, 3, 5, 7, 10, 14 and 21 after UUO. The expression of PAR
      2 mRNA and protein and alpha-smooth muscle actin (alpha-SMA) protein in
      tubulointerstitium was detected by RT-PCR and immunohistochemistry at each time
      point, respectively. The results showed that the PAR-2 expression in renal
      tubulointerstitium was increased progressively starting from 24 h to the day 14
      post-ligation, and it was significantly associated with the relative volume of
      interstitium and the positive area of alpha-SMA. PAR-2 was mainly expressed in
      renal tubule epithelial cells, especially in proximal tubular cells. It also
      located in renal capillary ansa, interstitial infiltrate cells and fibroblasts.
      It was concluded that PAR-2 was active in interstitial and tubular cells in the
      early phase of fibrotic process and played an important role in mediating the
      tubulointerstitial lesion after UUO.

PMID- 16463664
TI  - Efficacy and safety of risedronate sodium in treatment of postmenopausal
      osteoporosis.
AB  - To evaluate the efficacy and safety of risedronate sodium in treatment of
      postmenopausal osteoporosis, one-year randomized, double blind clinical trial was
      performed among 54 women with postmenopausal osteoporosis. The changes were
      compared in bone mineral density (BMD), bone metabolism markers and adverse
      events after 12 months oral administration of risedronate sodium. BMD was
      measured by dual energy X-ray absorptionmetry (DEXA) and bone turnover marker was
      detected. The results showed that there was a significant increase in BMD of the
      lumbar spine (3.29% +/- 1.18%, 4.51% +/- 1.64% respectively) after 6 and 12
      months in the risedronate treatment group versus placebo control group (-0.62% +/
      0.24%, 0.48% +/- 0.18% respectively). Bone turnover was decreased to a stable
      nadir over 6 and 12 months for resorption markers [N-Telopeptide (NTx), P < 0.05]
      and over 12 months for formation marker (ALP, P < 0.05; BGP, P < 0.05). The
      safety profile of risedronate sodium was similar to that of placebo. There were
      no trends toward increased frequency of any adverse experience except for
      gastrointestinal symptoms (7.1%), rash (7.1%) and hematuria (3.6%), which were
      usually mild, transient, and resolved with continued treatment. It was concluded
      that risedronate was an efficacious and safe drug in treatment of postmenopausal
      osteoporosis.

PMID- 16463665
TI  - Dynamic observation of liver fibrosis in mice infected with Schistosoma japonica.
AB  - The expression of TNF-alpha in the liver at different periods post Schistosoma
      japonica infection and the effect on liver fibrosis after supplementary injection
      of these cytokines were investigated. The mice infected with schistosome
      cercariae were divided into 3 groups: normal control group, TNF-alpha-untreated
      infection group and TNF-alpha-treated infection group. ABC immunohistochemistry
      and pathologic image multimedia quantification system were applied to dynamically
      detect the activity of TNF-alpha. The results showed that the levels of TNF-alpha
      in the liver in TNF-alpha-untreated infection group were slowly decreased with
      prolongation of infection time (from 8th, 11th, 14th to 18th week), while in the
      TNF-alpha-treated infection group, those were increased significantly after
      intraperitoneal injection of TNF-alpha at 6th week after infection. At first to
      8th week after the final injection of TNF-alpha, the intrahepatic TNF-alpha
      levels in the TNF-alpha-treated infection group were significantly higher than in
      the other two groups (P < 0.01), and the granulomatous inflammation and fibrosis
      in the liver were also milder in the normal control group. It was concluded that
      at the early stage of Schistosoma japonica infection mouse liver mainly released
      Th1 cytokine and TNF-alpha from Th1 activated macrophages. Six weeks after
      infection (post egg deposition), exogenous supplement with intraperitoneal
      injection of TNF-alpha could induce the enhanced expression of Th1 cytokines and
      alleviate the liver granulomatous inflammation and fibrosis.

PMID- 16463666
TI  - Immune vasculitis induced atherosclerosis.
AB  - The relationship between immune vasculitis and atherosclerosis was studied. The
      experimental model of weanling rabbits for immune vasculitis was reproduced by
      intravenous injection of 10% bovine serum albumin. There were 6 groups: group A,
      25 weanling rabbits with immune vasculitis subject to coronary arteriography;
      group B, 10 normal mature rabbits subject to coronary arteriography; group C, 10
      weanling rabbits subject to coronary arteriography; group D, 8 weanling rabbits
      with vasculitis and cholesterol diet; group E, 8 weanling rabbits receiving
      single cholesterol diet; group F: 8 weanling rabbits receiving basic diet. Four
      weeks later, coronary arteriography was performed in groups A, B and C. The
      rabbits in groups D, E and F were sacrificed for the study of pathological
      changes in the coronary artery after 12 weeks. The results showed that the
      dilatation of coronary artery occurred in 6 rabbits of group A, but in groups B
      and C, no dilatation of coronary artery appeared. In comparison with group E,
      more severe atherosclerosis occurred in group D, showing the thickened plaque,
      fibrous sclerosis and atherosclerotic lesion. Percentage of plaques covering
      aortic intima, incidence of atherosclerosis of small coronary arteries and degree
      of stenosis of coronary arteries were significantly higher in group D than in
      group E (P < 0.01). No atherosclerosis changes were found in group F. It was
      concluded that in the acute phase, the serum immune vasculitis can induce the
      dilatation of coronary artery of some weanling rabbits, and aggravate the
      formation of atherosclerosis in rabbits fed with cholesterol diet. Immune
      vasculitis is a new risk factor of atherosclerosis and ischemic heart disease.

PMID- 16463667
TI  - Expression of cyclooxygenase-2 in ovarian cancer cell lines.
AB  - To investigate the expression of cyclooxygenase-2 (COX-2) in ovarian cancer cell
      lines, RT-PCR and immunocytochemistry were used to detect the expression of COX-2
      in 5 ovarian cancer cell lines. The expression of COX-2 mRNA and protein was
      detected in all 5 cell lines. It is suggested that COX-2 is expressed in ovarian
      cancer cell lines, which provides a basis for the chemoprevention of ovarian
      cancer.

PMID- 16463668
TI  - Childhood Henoch-Schonlein purpura nephritis and IgA nephropathy: one disease
      entity?--A clinico-pathologically comparative study.
AB  - In order to characterize their relationship through clinicopathological
      comparison between IgA nephropathy and Henoch-Schonlein purpura nephritis (HSPN),
      31 children with IgA nephropathy aged between 3 to 15 years and 120 children with
      HSPN aged between 4 to 15 years were compared with each other in clinical
      manifestation, blood biochemistry, serum immunology and follow-up study. Renal
      pathological findings under light microscope, immunofluorescence and electronic
      microscope were analyzed and also compared between 31 children with IgA
      nephropathy and 32 biopsied children with HSPN. The results showed that the onset
      age was over 12 years in 25.8% children with IgA nephropathy, but only 10% in
      HSPN (P < 0.05). The clinical patterns of IgA nephropathy and HSPN were similar,
      but extra-renal manifestations were more often in HSPN, all of them had skin
      purpura, 59% had gastrointestinal symptoms and 47% suffered from arthralgia,
      compared with only abdominal pain in 3.2% children with IgA nephropathy. The
      renal pathological investigation showed global sclerosis in 35.5% of IgA
      nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9% of IgA nephropathy and
      6.3% of HSPN, but endothelial proliferation in 65.6% of HSPN and 29% of IgA
      nephropathy (all P < 0.01). Thin basement membrane nephropathy was only found in
      6.5% children with IgA nephropathy, no in HSPN. The electronic dense deposits in
      HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial
      area and even intra basement membrane, but it was dense, lumpy and mostly limited
      in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were
      found in 81.2% of HSPN, and overwhelming IgG deposits in 12.5% of HSPN with
      relatively weak IgA deposits, moreover 6.3% of HSPN showed linear IgG deposits in
      glomerular capillary. Totally 71.9% of HSPN had IgG deposits in glomeruli and
      only 19.4% of IgA nephropathy showed glomerular IgG deposits (P < 0.01). No IgG
      deposit was observed in 81.6% of IgA nephropathy, among them most showed IgA and
      IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG
      deposits couldn't be found in IgA nephropathy. Mean 20 months follow-up showed
      complete remission in 72.5% of HSPN, but only 19.4% in IgA nephropathy after 34
      months follow-up. Moreover, 64.5% of IgA nephropathy had consistent hematuria and
      proteinuria and 16.1% had active nephritides (P < 0.05). It was concluded that
      significant clinico-pathological difference was found between HSPN and IgA
      nephropathy, which didn't support the one disease entity hypothesis. HSPN and IgA
      nephropathy are probably two diseases with similar immune abnormalities.

PMID- 16463670
TI  - Influence of Radix Isatidis on the endotoxin-induced release of TNF-alpha and IL
      8 from HL-60 cells.
AB  - The effects of active antiendotoxin chemical fraction isolated from Radix
      Isatidis (fraction D) on TNF-alpha and IL-8 secretion in HL-60 cells induced by
      lipopolysaccharide (LPS) were studied. The appropriate densities of cell
      suspension and fraction D solution were determined by MTT colorimetric method.
      Fraction D and LPS were added to HL-60 cell suspension with three different
      methods respectively. The contents of TNF-alpha and IL-8 in the cultured
      supernatant induced by LPS were detected by using ELISA method. The results
      showed that the absorbance (A) was directly proportional to the number of cells
      and the linearity was good in the range from 0.25 x 10(5) to 2 x 10(5) cell/mL
      cell suspension. The fraction D significantly inhibited the oversecretion of TNF
      alpha and IL-8 in HL-60 cells induced by LPS at the concentration of 7.812 mg/mL
      which had no cytotoxicity. It was indicated that the antiendotoxin mechanism of
      the active fraction from Radix Isatidis was contributed to the inhibition of the
      oversecretion of cytokines induced by LPS.

PMID- 16463669
TI  - Effects of triptolide on the expression and activity of NF-kappaB in synovium of
      collagen-induced arthritis rats.
AB  - The expression and activity of NF-kappaB in the synovium of collagen-induced
      arthritis (CIA) rats was detected in order to investigate the possible
      therapeutic effects of triptolide on rheumatoid arthritis (RA). The experimental
      Wistar rat model of CIA was set up by intradermal injection of emulsion of bovine
      collagen II and the successful rate of setting-up models was evaluated by
      arthritis index (AI). Rats were grouped randomly into three groups: normal, model
      and treatment group. The expression of TNF-alpha and IL-6 in synovial fluid was
      detected by ELISA, and the expression and activity of NF-kappaB in synovium by
      immunohistochemistry method and by electrophoretic mobility shift assay (EMSA)
      respectively. As compared with normal group, the expression of TNF-alpha and IL-6
      in synovia (P < 0.05), and the expression and activity of NF-kappaB (P < 0.05) in
      synovium were increased in model group. There was statistical difference in above
      mentioned indexes between model group and treatment group. Triptolide may play a
      protective role in RA via downregulating the expression and activity of NF-kappaB
      in synovium.

PMID- 16463671
TI  - Anti-tumor effect and mechanism of SEA-Fab' coupled protein on gastric tumor.
AB  - The anti-tumor effect and mechanism of SEA-Fab' coupled protein on gastric tumor
      was studied. The target cell Walker-256 was treated with SEA-Fab' synthesized
      chemically or SEA respectively for 24 h, 36 h or 72 h. PBMC+Walke-256 cells
      served as controls. The apoptotic index of SEA-Fab' against effector cells was
      detected. In the mouse gastric cancer models (n = 60), SEA-Fab', SEA and normal
      saline was injected in experimental group, SEA group and control group
      respectively. The occurrence and weight of tumor was observed. The results showed
      that the apoptotic index was significantly higher in the SEA-Fab' (34.6%-68.9%)
      and SEA group (15.5% -31.9%) than in PBMC+Walker-256 group (5.5%-12.8%) with the
      difference being significant (P < 0.01). And there was significant difference
      between SEA-Fab' group and SEA group (P < 0.01). The tumor weight in SEA-Fab',
      SEA and control groups was 3.64 +/- 0.53 g, 0.78 +/- 0.26 g and 0.49 +/- 0.17 g
      respectively with the difference being statistically significant between the SEA
      Fab' group, SEA group and the control group (P < 0.01). In the SEA-Fab's and SEA
      groups, there were CD4+ T and CD8+ T cell infiltrates, but in the cotnrol group,
      no or few T lymphocytes were seen in the mouse tumor tissue. It was concluded
      that SEA-Fab' was more effective to activate T lymphocytes to kill the tumor
      cells than SEA used alone. It was feasibility by using the monoclonal antibody as
      carrier to perform the targeted immunotherapy of gatric tumor.

PMID- 16463672
TI  - Expression of RECK gene and MMP-9 in hilar cholangiocarcinoma and its clinical
      significance.
AB  - In order to study the expression of transformation suppressor gene RECK and MMP-9
      in hilar cholangiocarcinomas and its clinical significance, and explore the roles
      of RECK gene in metastasis and invasion of hilar cholangiocarcinoma, the
      expression levels of RECK, and MMP-9 mRNA were detected by using reverse
      transcription-polymerase reaction in 42 paraffin-embedded samples of hilar
      cholangiocarcinomas and 10 samples of benign bile duct diseases. The results
      showed that in hilar cholangiocarcinoma tissues, the expression of RECK gene was
      0.235 +/- 0.062, significantly lower than in normal bile duct tissues (0.533 +/-
      0.024, P < 0.05). In hilar cholangiocarcinoma tissues, the expression of MMP-9
      (0.528 +/- 0.039) was significantly higher than in the normal tissues (0.311 +/-
      0.032, P < 0.05). The expression of RECK gene was closely related to the
      intrahepatic and surrounding organs invasion (P < 0.05). It was concluded that
      RECK gene could inhibit the expression of MMP-9 in hilar cholangiocarcinomas and
      closely correlated with the biological behaviors. The abnormal expression of RECK
      gene might be one of the molecular mechanisms of hilar cholangiocarcinoma
      metastasis.

PMID- 16463673
TI  - Impact of MAPK cascade pathway and P53 pathway upon liver transplant.
AB  - The change and the role of MAPK cascade pathway and P53 pathway after liver
      transplantation were explored. Thirty-four punctured donor liver specimens and 10
      normal liver specimens were classified as group A (no rejection, n = 10), group B
      (mild/moderate acute rejection, n = 10), group C (serious acute rejection, n =
      8), group D (chronic rejection/fibrosis, n = 6) and group E (control, n = 10). By
      using immunohistochemistry, the expression levels of mitogen activated protein
      kinase (MAPK), Ras and P53 proteins, and by in situ hybridization, MAPK and ras
      mRNA expression levels were detected. The results showed that the expression
      levels of MAPK and Ras proteins were increased by turns in groups A, B and C, and
      decreased by turns in groups D and E. The protein expression of P53 was higher in
      the treated groups. The expression of Ras, HSP70 mRNA was identical as that of
      protein. It is suggested that the MAPK cascade pathway and P53 pathway can
      protect the hepatocytes by different mechanisms after liver transplantation.
      MAPKs cascade pathway repairs hepatocyte injury or accelerates hepatocytes into
      proliferation or differentiation. P53 pathway blocks cell cycle within G1 phase
      to make hepatocyte repair or apoptosis to reduce disorder differentiation.

PMID- 16463674
TI  - Effects of cyclosporine A on angiotensin II-induced cardiomyocyte hypertrophy in
      neonatal rats.
AB  - The effects of cyclosporine A (CsA) on Angiontensin II (Ang II)-induced protein
      contents, c-fos protein levels and cytosolic Ca2+ level ([Ca2+]i) in cultured
      cardiomyocytes of neonatal rats were observed. Total protein contents were
      determined by Bradford method. The expression of c-fos protein was detected by
      Western blot. [Ca2+]i labeled with fluorescent probe Fluo-3/AM was measured under
      a laser scanning confocal microscope. The results revealed that as compared with
      control, the total protein contents were increased in cardiomyocytes treated with
      Ang II (10(-7) mol/ L), which could be inhibited by CsA in a dose-dependent
      manner. It was found that Ang II could increase the c-fos protein expression,
      which could be inhibited by CsA in a dose-dependent manner. Ang II induced the
      [Ca2+]i elevation in cardiomyocytes. CsA did not influence the resting
      intracellular Ca2+, but inhibited significantly the Ang II-induced [Ca2+]i
      elevation. It was concluded that CsA can suppress the Ang II-induced c-fos
      protein expression and [Ca2+]i elevation in single cardiomyocyte, which might
      play a role in the prevention of Ang II-induced cardiomyocyte hypertrophy by CsA.

PMID- 16463675
TI  - Dynamic observation on the effects of different suture techniques on the
      biomechanical properties in the healing of tendons.
AB  - To identify the best suture techniques for the tendon repair, the biomechanical
      properties of tendons sutured by different methods were dynamically examined. 140
      chickens were divided into 2 groups equally: group A and group B. The tendon of
      the right side was subjected to injury-repair process, and the tendons of the
      left sides served as controls in both groups. In group A, "figure-of-8" suture,
      modified Kessler suture and Bunnell suture were used for the 2nd to 4th paws
      respectively, while in group B, Kleinert suture, Tsuge suture and Ikuta suture
      were used. On the day 0, 3, 7, 14, 21, 28, 42 after operation, 10 animals were
      sacrificed and the flexor tendons of both sides were harvested for strength test.
      The results showed that the initial strength of the repaired tendons and the
      strength after 6 weeks following tendon cut were far below those of intact
      tendons, irrespective of suture techniques used. With the 6 techniques, the
      P(max) of tendons repaired by Tsuge suture was increased continually, reaching
      the highest value on the 42nd day. The P(max) of tendons sutured by the modified
      Kessler suture was slightly lower than that by Tsuge suture, but it was increased
      steadily in healing. The tendons repaired by figure-of-8 suture yielded the
      lowest P(max). It was concluded that Tsuge suture and modified Kessler suture
      were the best techniques for tendon repair.

PMID- 16463676
TI  - Effects of ligustrazine on the contraction of isolated rabbit corpus cavernosum
      strips.
AB  - To investigate the role of ligustrazine on relaxation of the isolated rabbit
      corpus cavernosum tissue in vitro, the effects of ligustrazine on the corpus
      cavernosum were observed by using experimental method of smooth muscle strips.
      Concentration-responses to phenylephine (PE) and KCl were recorded. The results
      showed that ligustrazine concentration-dependently depressed the contraction
      response of smooth muscle strips induced by PE. The maximum percentage relaxation
      of cavernosal strips by ligustrazine was 74.1% +/- 6.2% (compared with control:
      21.9% +/- 5.6%, P < 0.01). Ligustrazine concentration-dependently reduced the
      amplitude of the contraction induced by cumulative doses of PE or KCl, shifted
      the cumulative concentration response curves of PE and KCI to the right and
      depressed their maximal responses. It was concluded that ligustrazine could
      significantly relax the cavernosal muscle contraction induced by PE in vitro. The
      results suggested that ligustrazine inhibited calcium ion influx.

PMID- 16463677
TI  - Experimental study of excitability and autorhthmicity in urinary bladder detrusor
      of diabetes rats.
AB  - The changes in excitability and autorhthmicity of bladder detrusor in
      experimental non-insulin dependent diabetes mellitus (NIDDM) rats were observed.
      Sixty-nine NIDDM rats as NIDDM group and 69 normal rats as control group were
      enrolled into this experimental study. At 6th, 10th, 14th, 18th, 22nd and 26th
      week after the rats were injected last time, the changes in the excitability and
      autorhthmicity of detrusor strips in vitro were observed. The results showed that
      the threshold of the tension which made the detrusor strips contract was
      significantly higher in NIDDM group (0.716 +/- 0.325 g) than in control group
      (0.323 +/- 0.177 g) (F = 59.63, P < 0.001). At different stages, the threshold of
      the tension resulting the contract of the detrusor strips in NIDDM group was also
      higher than in control group. At 18th week after STZ injection, the frequency of
      spontaneous contract of the detrusor strips in NIDDM was significantly higher
      than in control group (P < 0.05), whereas at 22nd week, that in NIDDM group was
      significantly lower than in control group (P < 0.05). It was concluded that the
      decreased excitability of the bladder detrusor was the earliest and most obvious
      changes in bladder function in diabetes rats and the autorhthmicity had also
      changed at the early stage of diabetic bladder.

PMID- 16463678
TI  - Total arterial revascularization with internal mammary artery or radial artery pi
      graft configuration.
AB  - To investigate the clinical use of pi graft in total arterial revascularization
      and its outcomes, a retrospective analysis of 23 patients out of 1000 patients
      undergoing total arterial coronary bypass surgery with a pi graft between
      September 1994 and December 2004 was performed. In the selected patients for the
      management of triple vessel disease with middle diagonal/intermediate ramus
      disease such that a skip with the left internal mammary artery (LIMA) or radial
      artery (RA), the main stem of pi graft, to the left anterior descending coronary
      artery (LAD) will not work and the right internal mammary artery (RIMA) or right
      gastroepiploic artery (RGEA) cannot pick up the diagonal/intermediate ramus,
      hence the LAD and diagonal/intermediate ramus were grafted with a mini Y graft
      using the distal segment of LIMA, RIMA, RA or RGEA, together with the bilateral
      internal mammary artery (BIMA) or LIMA-RA T graft to compose pi graft. Twenty
      three patients (18 males, 5 females) underwent the pi graft procedure. There were
      no deaths or episodes of myocardial infarction, stroke, and deep sternal wound
      infection. One patient required reopening for controlling bleeding. Until the end
      of 2004, during a mean follow-up of 81.0 +/- 28.4 months, no angina needing re
      intervention or operative therapy or coronary related death occurred. In
      conclusion, in patients with specific coronary artery anatomy/stenosis, the BIMA
      (sometimes LIMA with RA or RGEA) pi graft can be successfully performed for total
      arterial revascularization with good midterm outcomes.

PMID- 16463679
TI  - Nerve growth factor modulate proliferation of cultured rabbit corneal endothelial
      cells and epithelial cells.
AB  - In order to investigate the effect of nerve growth factor (NGF) on the
      proliferation of rabbit corneal endothelial cells and epithelial cells, the in
      vitro cultured rabbit corneal endothelial cells and epithelial cells were treated
      with different concentrations of NGF. MTT assay was used to examine the clonal
      growth and proliferation of the cells by determining the absorbency values at 570
      nm. The results showed that NGF with three concentrations ranging from 5 U/mL to
      500 U/mL enhanced the proliferation of rabbit corneal endothelial cells in a
      concentration-dependent manner. 50 U/mL and 500 U/mL NGF got more increase of
      proliferation than that of 5 U/mL NGF did. Meanwhile, 50 U/mL and 500 U/mL NGF
      could promote the proliferation of the rabbit corneal epithelial cells
      significantly in a concentration-dependent manner. However, 5 U/mL NGF did not
      enhance the proliferation of epithelial cells. It was suggested that exogenous
      NGF can stimulate the proliferation of both rabbit corneal endothelial and
      epithelial cells, but the extent of modulation is different.

PMID- 16463680
TI  - Expression of TGF-beta2 mRNA and PCNA, FN protein in lens epithelial cells in age
      related nuclear and cortex cataract.
AB  - By using RT-PCR and immunohistochemistry, the expressions of transforming growth
      factor beta2 (TGF-beta2) mRNA, proliferating cell nuclear antigen (PCNA) and
      fibronection (FN) protein in lens epithelial cells (LECs) of age-related nuclear
      and cortex cataract were detected and compared. The results of RT-PCR revealed
      that the expression of TGF-beta2 mRNA was higher in cortex cataract than in
      nuclear cataract. Immunohistochemistry demonstrated that the expression of PCNA
      protein was lower and the expression of FN protein was higher in cortex cataract
      than in nuclear cataract. It was suggested that TGF-beta2, PCNA and FN might take
      important parts in the process of age-related cataract. Cortex cataract was
      related to the transdifferentiation of LECs, and nuclear cataract to the
      proliferation of LECs.

PMID- 16463681
TI  - Construction of prokaryotic expression plasmid of mtrC protein of Neisseria
      gonorrhoeae and its expression in E. coli.
AB  - In order to provide a rational research basis for detection of resistance of
      Neisseria gonorrhoeae to antimicrobial hydrophobic agents and study on the
      resistant mechanism of multiple transferable resistance (mtr) efflux system,
      plasmid pET-28a(+) encoding mtrC gene was constructed and the related target
      protein was expressed in Escherichia coli (E. coli) DE3. The fragments of mtrC
      gene of Neisseria gonorrhoeae from the standard strains were amplified and cloned
      into prokaryotic expression plasmid pET-28a(+) with restriction endonuclease to
      construct recombinant pET-mtrC which was verified by restriction endonuclease and
      DNA sequencing. The recombinant was transformed into E. coli DE3 to express the
      protein mtrC induced by IPTG. The results showed mtrC DNA fragment was proved
      correct through restriction endonuclease and DNA sequencing. Its sequence was
      99.5% homologus to that published on GeneBank (U14993). A 48.5 kD fusion protein
      which was induced by IPTG was detected by SDS-PAGE. It was concluded that the
      construction of prokaryotic expression plasmid of mtrC protein of Neisseria
      gonorrhoeae was correct and the fusion protein was successively expressed in E.
      coli.

PMID- 16463682
TI  - Detection of ATP2C1 gene mutation in familial benign chronic pemphigus.
AB  - The ATP2C1 gene mutation in one case of familial benign chronic pemphigus was
      investigated. One patient was diagnosed as familial benign chronic pemphigus by
      pathology, ultrastructral examination and clinical features. Genomic DNA was
      extracted from blood samples. Mutation of ATP2C1 gene was detected by polymerase
      chain reaction (PCR) and DNA sequencing. The results showed that deletion
      mutation was detected in ATP2C1 gene in this patient, which was 2374delTTTG. No
      mutation was found in the family members and normal individuals. It was concluded
      that the 2374delTTTG mutation in ATP2C1 gene was the specific mutation for the
      clinical phenotype for this patient and was a de novo mutation.

PMID- 16463683
TI  - Oligosaccharide and creatine supplementation on glucose and urea nitrogen in
      blood and serum creatine kinase in basketball athletes.
AB  - The effects of oligosaccharide and creatine (Cr) supplementation on glucose,
      lactic acid and urea nitrogen levels in blood and activity of serum creatine
      kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups:
      group A (supplementation of Cr alone), group B (supplementation of
      oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D
      (placebo control group). By using orthogonal L4 table (2(3)), the experiment was
      performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr
      and their correlation. Each factor had two levels: supplementation and no
      supplementation. The results showed that the supplementation of CHO or Cr alone,
      combined supplementation of CHO and Cr could significantly reduce the glucose,
      urea nitrogen levels in blood and serum CK activity after competition in the
      athletes. Moreover, the effects of combined supplementation of CHO and Cr were
      more satisfactory. It was concluded that supplementation of CHO and Cr could
      promote the recovery of physical performance and athletic abilities after
      athletics in basketball athletes.

PMID- 16463684
TI  - Assessment of coronary flow velocity reserve by noninvasive transthoracic Doppler
      echocardiography in patients with angiographically normal coronary arteries.
AB  - The measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler
      echocardiography (TTDE) with invasive intracoronary Doppler flow wire technique
      (ICD) was validated and the pathological factors which influence CFVR in patients
      with angiographically normal coronary arteries were analyzed. CFVR was determined
      successfully in left anterior descending artery (LAD) in 37 of 40 patients with
      angiographically normal coronary arteries (men 22, women 15, age 20-75 years,
      mean age 54 +/- 12 years). Coronary flow velocity was measured in the distal LAD
      by TTDE with contrast enhancement at baseline and during intravenous adenosine
      infusion of 140 microg/kg per min within 48 h after ICD technique. Average peak
      velocity at baseline (APVb), average peak velocity during hyperemia (APVh) and
      CFVR determined from TTDE were correlated closely with those from ICD
      measurements (APVb: y = 0.64x + 5.04, r = 0.86, P < 0.001; APVh: y = 0.63x +
      14.36, r = 0.82, P < 0.001; CFVR: y = 0.65x + 0.92, r = 0.88, P < 0.001). For
      CFVR measurements, the mean differences between TTDE and ICD methods were 0.12 +/
      0.39. CFVR in patients with history of hypertension was significantly lower than
      that in patients without history of hypertension (P < 0.05). Intravascular
      ultrasound (IVUS) was performed in 34 patients. Plaque formation was found in LAD
      by IVUS in 17 (50%) patients. No significant difference in CFVR was found between
      the patients without plaque formation (3.11 +/- 0.49) and those with plaque
      formation (2.76 +/- 0.53, P = 0.056). It is suggested that TTDE with contrast
      enhancement provides reliable measurement of APV and CFVR in the distal LAD. The
      early stage of atherosclerosis could be detected by IVUS, which may be normal in
      angiography. CFVR is impaired in patients with history of hypertension compared
      with that in patients without history of hypertension.

PMID- 16463685
TI  - An early continuous experimental study on magnetic resonance diffusion-weighted
      image of focal cerebral ischemia and reperfusion in rats.
AB  - The chronological and spatial rules of changes during focal cerebral ischemia and
      reperfusion in different brain regions with magnetic resonance diffusion-weighted
      imaging (DWI) in a model of occlusion of middle cerebral artery (MCAO) and the
      development of cytotoxic edema in acute phase were explored. Fifteen healthy S-D
      rats with MCA occluded by thread-emboli were randomly divided into three groups.
      15 min after the operation, the serial imaging was scanned on DWI for the three
      groups. The relative mean signal intensity (RMSI) of the frontal lobe, parietal
      lobe, lateral cauda-putamen, medial cauda-putamen and the volume of regions of
      hyperintense signal on DWI were calculated. After the last DWI scanning, T2 WI
      was performed for the three groups. After 15 min ischemia, the rats was presented
      hyperintense signals on DWI. The regions of hyperintense signal were enlarged
      with prolonging ischemia time. The regions of hyperintense signal were back to
      normal after 60 min reperfusion with a small part remaining to show hyperintense
      signal. The RMSIs of parietal lobe and lateral cauda-putamen were higher than
      that of the frontal lobe and medial cauda-putamen both in ischemia phase and
      recanalization phase. The three groups were normal on T2 WI imaging. DWI had good
      sensitivity to acute cerebral ischemia, which was used to study the chronological
      and spatial rules of development of early cell edema in ischemia regions.

PMID- 16463686
TI  - Value of acceleration flow in the left anterior descending coronary artery for
      the detection of coronary artery stenosis by transthoracic coronary color Doppler
      echocardiography.
AB  - Whether the localized flow acceleration occurs in the resting stenotic left
      anterior descending coronary artery was explored and its value for detection of
      coronary stenosis estimated. Blood flow in the left anterior descending coronary
      arteries in 45 patients was detected by transthoracic color Doppler
      echocardiograph and multipoint pulse Doppler spectrums were recorded in the same
      segment. The ratio of the maximal peak diastolic velocity to the minimal peak
      diastolic velocity was calculated. The ratio > or = 1.5 was the cutoff value for
      the presence of localized acceleration flow. There were 23 patients with
      localized acceleration flow examined by echocardiography. Twenty of them were
      found to have luminal diameter stenosis (60% - 98%) in the left anterior
      descending coronary arteries by coronary angiography and 3 patients were normal.
      There were 22 patients without localized acceleration flow examined by
      echocardiography. Eighteen of them had no or < 60% stenosis. Four patients had
      serious stenosis (> or = 95%) or occluded segments in the left anterior
      descending coronary arteries on coronary angiography. The ratio of the maximal
      peak diastolic velocity to the minimal peak diastolic velocity was significantly
      higher in patients with left anterior descending coronary artery stenosis than
      that in those without stenosis (1.9 +/- 0.3 vs 1.3 +/- 0.2, P < 0.01) and it
      correlated significantly with left anterior descending coronary artery stenosis
      (r = 0.77, P < 0.01). The specificity by using the ratio > or = 1.5 for stenosis
      detection was 85.7% (18/ 21), and the sensitivity was 83.3% (20/24). This study
      demonstrated that local blood flow velocity was increased in the resting stenotic
      left anterior descending coronary artery. Transthoracic color Doppler
      echocardiography is a reliable noninvasive method to detect localized
      acceleration flow in the left anterior descending coronary artery stenosis and it
      is useful in the noninvasive diagnosis of stenosis in the left anterior
      descending coronary artery.

PMID- 16463687
TI  - MR features of regenerative nodules and dysplastic nodules in the cirrhotic
      liver.
AB  - In order to study MR features of the regenerative nodule (RN) and dysplastic
      nodule (DN) of the cirrhotic liver, 26 cases of cirrhotic liver with RNs and DNs,
      of which 8 cases accompanied with hepatocellular carcinoma, were subjected to
      MRI. Eighteen of 26 cases underwent additional enhanced MRI with administration
      of Gd-DTPA on T1WI and 10 of the 18 cases did additional SPIO (Feridex)
      enhancement on T2WI. Clinical data showed normal level of alpha-fetoprotein in 18
      cases except 8 cases accompanied with HCC. The results showed that 12 cases had
      RNs with nodules measuring < 1 cm. The MR appearance of those RNs showed
      isointensity on T1WI and hypointensity on T2WI. The intensity of those RNs was
      isointense to the surrounding hepatic parenchyma on enhanced MRI with
      administration of Gd-DTPA or SPIO. Among the 14 cases of DNs, 8 cases had nodules
      measuring 1-3 cm in size and 6 had macroregenerative nodule measuring > 3 cm. In
      8 cases with DNs measuring 1-3 cm in size, 5 cases appeared hyperintense on T1WI
      and hypointense on T2WI as well as the enhancement as that of nodules with < 1 cm
      in size; and the remaining 3 cases appeared hypointense on T1WI and hyperintense
      on T2WI, and were not isointense to the surrounding hepatic parenchyma on
      enhanced MRI but hyperintense on SPIO enhanced MRI. In 6 cases of
      macroregenerative nodule measuring > 3 cm in size, 2 cases appeared hyperintense
      to the surrounding hepatic parenchyma on T1, T2WI and enhanced MRI; 4 cases
      showed hyperintense on T1WI, and hypointense on T2WI and enhanced MRI. Sometimes,
      normal vessels were seen to pass through the surface of macroregenerative
      nodules. It was suggested that RNs of cirrhosis had features on MRI that usually
      allow distinction from hepatocellular carcinoma but not always from dysplastic
      nodules (DNs). A helpful distinction between HCC and DNs is that the latter are
      almost never hyperintense on T2WI. Additionally, low grade DNs appear hypointense
      on SPIO enhanced MRI.

PMID- 16463688
TI  - Analysis of proteomic components of sera from patients with uremia by two
      dimensional electrophoresis and matrix assisted laser desorption/ ionization time
      of flight mass spectrometry.
AB  - The different sera proteomic components between uremia patients and normal
      subjects were studied through two-dimensional gel electrophoresis technique.
      Immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis (2DE),
      silver staining, ImageMaster 2D 5.0 analysis software, matrix assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF-TOF-MS) and IPI
      human database searching were used to separate and identify the proteome of the
      sera from the patients with uremia. The results showed that satisfactory 2DE
      patterns of the serum proteins were obtained. Twenty-six protein spots showed
      significant difference in quantity in uremia patients, and 20 protein spots were
      identified by MALDI-TOF-TOF-MS. It was concluded that good reproducibility could
      be obtained by applying immobilized pH gradient 2DE to separate and identify the
      proteome in serum, which provided the foundation for the further study on uremia
      toxins pertaining to protein.

PMID- 16463689
TI  - Demand for and accessibility to reproductive health service of urban floating
      population.
AB  - The demand for knowledge of productive health and the current status of
      productive health services provided by relevant governmental institutions were
      qualitatively and quantitatively studied. The study identified the key factors
      that influenced the demand for the productive health services and results of the
      services. It also discussed the effective approaches to control, planning and
      sustainable development of the reproductive health services for the floating
      populations.

PMID- 16463690
TI  - Application of VPN technique in the construction of public health information
      system.
AB  - Data communication and sharing of five level network of Public Health Information
      System, i.e. nation, province, district (city), county, and town, as far as to
      the countryside level were described, and how to apply the three solutions, i.e.
      Access VPN, Intranet VPN, and Extranet VPN of VPN technique to achieve the
      appropriation of the public network was also presented.

PMID- 16463691
TI  - Hepatic angiomyolipoma demonstrating similar imaging characteristics as
      hepatocellular carcinoma: one case report.

PMID- 16463692
TI  - Prednisone combined with interferon for the treatment of one case of generalized
      granulomatous slack skin.

PMID- 16463693
TI  - [Early, noninvasive diagnostic of osteoporosis in men].
AB  - Osteoporosis is the most frequent metabolic bone disease. Until recently it was
      believed to mainly affect women in menopause. A review of the literature
      indicates that a lot of the research to date on women. The patogenesis of bone
      loss in men has not been explained yet. It has not been determined what is the
      contribution of androgens as opposed to environmental factors and stimulants. The
      behaviour of bone turnover markers during ageing and their role in diagnosing the
      risk of osteoporosis development and fractures in men are not clear. The
      objective of the paper was to evaluate bone metabolism markers and to determine
      their relevance in early diagnosis of osteoporosis in men, and to determine any
      possible impact of testosterone concentration on bone mass. The study covered 100
      volunteers-males, aged 40-85. All were subjected to a densitometric examination,
      using theDEXA method, of three regions of the osseous system: lumbar spine in
      anterior-posterior height, proximal femur, distal radius. Based on these results,
      subjects were divided into three groups: without osteoporosis, with osteopenia
      and with osteoporosis. In all men the serum level of the following was marked: 1)
      3 markers of bone formation: osteocalcin (BGP), bone alkaline phosphatase (b-ALP)
      and Procollagen I Aminoterminal propeptide (PINP); 2) 2 markers of bone
      resorption: Collagen Type I Crosslinked C-telopeptide (Ctx) and Tartarate
      Resistant Acid Phosphatase (TRAP); 3) testosterone. The results obtained were
      subjected to thorough statistical analisis. Mean concentrations of bone
      metabolism, testosterone and calcium consumption in the groups examined were
      compared by mean of ANOVA variance analysis and the smallest significant
      difference test. Relationship between markers of bone resorption and formation,
      testosterone level and bone mineral density (BMD) were shown by means of Pearson
      linear correlation. The relevance of markers in the diagnosing of osteoporosis in
      men was evaluated by means of the ROC curves. The results obtained lead to the
      following conclusions: Among the markers of bone turnover analysed, Collagen Typ
      I Crosslinked C-telopeptide (Ctx-serum) is the most useful marker in the
      diagnosis of osteoporosis in men, followed by Tartarate Resistant Acid
      Phosphatase (TRAP) and osteocalcin (BGP). There is no relationship between bone
      mineral density and serum testosterone level.

PMID- 16463694
TI  - [Activity of N-acetylo-beta-hexosamninidase in joint fluid from knee and serum of
      patients with rheumatoid arthritis and osteoarthritis].
AB  - N-acetyl-beta-hexosoaminidase (Hex) is a lysosomal enzyme which releases N
      acetylaminohexose from non reducing end of glycosaminoglycans, glycoproteins and
      glycolipids, taking part in degradation of these substances. It is not known what
      role Hex plays in the degradation of joints in rheumatoid arthritis and
      osteoarthritis. The aim of our work was evaluation of Hex activity in synovial
      fluid and serum of patients with rheumatoid arthritis and osteoarthritis. The
      investigation was performed on material taken from 28 patients with rheumatoid
      arthritis aged 22-74 years with III or IV stage of disease and 26 patients with
      osteo-arthritis aged 41-75 years. The synovial fluid was collected from the knee
      joint during puncture. Hex activity was also determined in serum of healthy
      people at the age 25-40 years which constitute a control group. Hex activity was
      determined by the method of Chatterjee et al. modified by Zwierz et al. The
      concentration of Hex activity in synovial fluid of patients with rheumatoid
      arthritis was 15.2 nmol/ml/min and 3-4 times excedeed the serum value in these
      patients. In osteoarthrosis patients Hex concentration in synovial fluid was 6.15
      nmol/ml/min. In serum of all investigated groups, concentration of Hex activity
      was 4.0-4.7 nml/ml/min. The specific activity of Hex (calculated as a constant
      amount of protein) in synovial fluid of patients with rheumatoid arthritis was
      significantly higher than in serum of these persons (p<0.017 and 0.014
      respectively).

PMID- 16463696
TI  - [Ambulatory cardiac rehabilitation and selected quality of life parameters among
      men with coronary artery disease].
AB  - BACKGROUND: Regular physical activity plays an important role in both primary and
      secondary prevention of cardiovascular disease. AIM: The aim of this study was to
      asses influence of leisure-time physical activity on selected quality of life
      parameters among men with coronary artery disease participating in ambulatory
      cardiac rehabilitation. MATERIAL AND METHODS: Thirty men with coronary heart
      disease who were engaged 7.0 +/- 2.9 years in physical activity rehabilitation
      program were assessed (Group A). This group was compared with 57 men (Group B)
      who did not participate in any formal exercise training. Physical activity was
      assessed by the interviewer-administrated Seven-Day Physical Activity Recall
      (SDPAR). Quality of life and subjective health state was determined by
      standardized questionnaire EuroQol 5D. RESULTS: Level of leisure time physical
      activity influence quality of life in study participants. Moreover in both groups
      subjects with 0.0 kcal/week energy expenditure on leisure time sport activities
      reported significantly lover subjective health state scores comparing to patients
      with higher level of leisure-time physical activity. CONCLUSIONS: This study
      demonstrates that cardiac rehabilitation lead to increase recreational physical
      activity among patients with heart artery disease and improve their quality of
      life.

PMID- 16463695
TI  - [Factors influencing signal-averaged ECG parameters in hemodialysis patients].
AB  - The aim of the present study was to estimate the influence of hemodialysis
      process (HD) on the signal-averaged ECG (SAECG) parameters and to evaluate
      possible factors promoting SAECG parameters disturbances in the group of
      hemodialysis patients (HD-pts). 55 selected HD-pts entered the study. SAECG
      parameters (QRS duration, root-mean-square of the terminal 40 ms of the QRS-
      RMS40, low-amplitude signal duration--LAS40), were measured pre and postdialysis.
      Total (TBW), extracellular (ECW) and intracellular body water (ICW) calculated
      per kg of HD-pts body weight were estimated pre and postdialysis by using whole
      body bioimpedance. Two dimentional echocardiography was performed before HD.
      Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha, CRP and intact
      parathormon were measured before HD. LP were found only before HD in 12.73% of
      patients. HD induced the decrease of LAS40 duration and the increase of RMS40
      value in the of group of LP positive HD-pts (p<0.001 in both cases). The values
      of TBW and ECW calculated per kg of body weight as well as IL-6 and CRP levels
      were significantly higher in the LP positive in comparison with the LP negative
      patients (p=0.006 and 0.004 respectively). Induced by HD changes of RMS40
      correlated with pre vs postdialysis values of TBW (r=0.499, p=0.001) and ECW
      (r=0.556, p<0.001) calculated per kg of body weight. Our study revealed that,
      that abnormal SAECG parameters and LP are frequently detected in HD-pts. The
      presence of LP in HD-pts in great part depends on the functional abnormalities
      (especially on the HD-pts hydration status) corrected by the HD process. The
      clinical significance of the proinflammatory factors (IL-6 and CRP) needs further
      investigation.

PMID- 16463697
TI  - [Effect of incremental cycling exercise performed before and 24 hours after blood
      withdrawal on the concentration of morphologic elements of blood in young health
      men].
AB  - The aim of this study was to evaluate the effect of incremental cycling exercise
      test performed before and 24 hours after blood donation (withdrawal of 450 ml of
      blood) on the plasma volume and concentration of morphologic elements of blood.
      Thirteen subjects (mean +/- SD), age 23 +/- 3 years; body mass 75 +/- 10 kg; BMI
      23.4 +/- 2 kg x m(-2); VO2max 2903 +/- 334 ml x min(-1), volunteered for this
      study. The exercise test started at the power output of 20 W with an increase by
      20 W every 3 minutes--until exhaustion. This test was performed once in the
      control study (7-12 days before blood donation) and repeated 24 hrs after blood
      donation. The blood samples were taken from the antecubital vein, in a sitting
      position (1) at rest, (2) at the stage of 100 W power output, (3) at the end of
      the test (the stage of exhaustion) and (4) at 2 hours after the end of the test.
      The changes in plasma volume were evaluated according to changes in hemoglobin
      and hematocrit concentrations. The significance of differences in the studied
      variables were tested using Wilcoxon test. At the end of the exercise test a
      significant (p<0.05) decrease in plasma volume was found in both study. It
      amounted to--11.1 +/- 2.9% in the control study, and to--13.0 +/- 3.9% after
      blood donation. Within 2 hours after the end of the exercise test plasma volume
      returned to the pre-exercise value in the control study and exceeded the pre
      exercise value by 3.9 +/- 6.7% (p<0.05) in the study performed after blood
      donation. The MCV, MCH, and MCHC values were not affected by the exercise
      performed before and after blood donation. In the control study, at the end of
      the incremental exercise test a significant increase in the leukocyte, lymphocyte
      and thrombocyte count was found. At 2 hours after exercise thrombocytes count
      returned to the pre-exercise level, whereas the exercise-induced leucocytosis
      remained at the end-exercise level. The lymphocyte count decreased to lymphopenic
      level. During the incremental exercise test performed after blood donation the
      changes in the concentration of the studied morphologic elements of blood were
      similar as in the control study. The only difference was noticed in the changes
      of lymphocyte count which returned to the pre-exercise level within 2 hours after
      exhaustion. Taking into consideration the changes in plasma volume it was found
      that during the incremental exercise tests (both in the control study and after
      blood donation) there was a significant (p<0.05) extra vascular escape of
      erythrocytes and thrombocytes. This was accompanied by a significant accumulation
      of neutrophils and lymphocytes in circulating blood. At 2 hours after the end of
      exercise, neutrophils count increases and lymphocytes migrate into peripheral
      lymphoid tissues, causing lymphopenia.

PMID- 16463698
TI  - [Oxidative stress evaluation in chronic hepatitis C pathogenesis].
AB  - The aim of this study was oxidative stress evaluation as reflected by antioxidant
      status and lipid peroxidation products levels in plasma and erythrocytes from CHC
      patients (chronic hepatitis C patients). Antioxidant status, markers of lipid
      peroxidation and liver function were measured in erythrocytes and plasma from 29
      CHC patients and from 26 matched healthy controls. Plasma and erythrocytes MDA
      (malondialdehyde) levels were statistically decreased in CHC patients as compared
      with healthy controls while erythrocytes CuZnSOD (superoxide dismutase-
      cytoplasmic enzyme contains copper and zinc) activity was statistically increased
      in CHC patients as compared to healthy subjects. Plasma MDA levels correlated
      positively with AST (aspartate aminotransferase), ALT (alanine aminotransferase),
      aldolase and LDH (lactate dehydrogenase) activity. GPX (glutathione peroxidase)
      activity correlated negatively with erythrocytes and plasma MDA levels and
      CuZnSOD activity correlated negatively with LDH, aldolase, AST activity and with
      plasma MDA levels. CONCLUSIONS: Results of antioxidant status in CHC patients
      indicate oxidative stress development and efficient function of intracellular
      antioxidants.

PMID- 16463699
TI  - [A survey of hospice home care at St. Lazarus Hospice in Krakow, Poland in the
      years 1994-1997].
AB  - Between 1994-1997 the Pain and Palliative Care Out-Patient Clinic founded by the
      Society of Friends of the Sick Hospicium in Krakow undertook hospice home care of
      870 cancer patients. Retrospective evaluation of their files revealed that 48.2%
      of patients on admission were aware of their diagnosis and 61.2% of families did
      not discuss it with patients. During that time, 735 home care patients died and
      83.5% of them died in their homes. During the same time, among the cancer
      patients not admitted to hospice home care in the city of Krakow, only 23.7% died
      at home and the rest in institutions. In spite of demonstrated adequate home
      care, 16.5% of home care patients were admitted to the local hospital, which
      suggests the need for stationary hospice or palliative care ward cooperation.

PMID- 16463701
TI  - [Neurological picture and 1H MRS in 4 children with hypoparathyroidism].
AB  - Hypoparathyroidism can result from lack or decreased secretion of parathormon
      (PTH) or from defective responsiveness of effector organs to PTH. Neurological
      signs of hypoparathyroidism include symptomatic or latent tetany, seizures, in
      the case of basal ganglia and cerebellar calcifications also choreoatetosis,
      parkinsonism and cerebellar syndrome. Seizures may occur at any age and are
      usually generalized tonic-clonic ones. They may also precede other signs of
      impaired function of extrapyramidal system. The aim of the study was the
      assessment of neurological signs in children with hypoparathyroidism and also the
      evaluation of different neuroimaging procedures especially magnetic resonance
      spectroscopy. In the recent two years 4 children were diagnosed as suffering from
      hypoparathyroidism. The cause for admitting children were paroxysmal states.
      Because of drug-resistant epilepsy antiepileptic drugs have been administered in
      one child for 8 years. In one case during the neurological examination signs of
      cerebellar syndrome were observed. EEG showed paroxysmal changes in three cases.
      Performed computed tomography (CT) of the head revealed basal ganglia
      calcifications. In the child with ataxia magnetic resonance imaging (MRI)
      demonstrated small atrophic areas in the cerebellum. The neuroimaging diagnostics
      was supplemented by the 1H magnetic resonance spectroscopy (MRS). The spectra
      were recorded from the areas localized within subcortical nuclei as well as from
      frontal (white matter) and temporal lobes. In case of all the 1H MRS spectra
      obtained from the subcortical nuclei regions significant decrease in the NAA/tCr
      ratio was observed which could reflect the reduced concentration of N
      acetyloaspartate, known as a neurons marker. All the metabolic profiles obtained
      from the spectra point to severe metabolic disturbances. The applied therapy
      (calcium, magnesium, Vit D3 preparations) allowed for seizures disapearance.

PMID- 16463700
TI  - [Disturbances of thyroid function in adult population of the city of Cracow
      followed up for ten years observation].
AB  - The aim of the study was to define disturbances of thyroid function in adult
      population of the city of Cracow followed up for ten years. The analysis included
      the results obtained from 891 individuals, 571 females and 320 males aged 18-78
      years examined prior to and after implementation of the obligatory model of
      iodine prophylaxis (years 1989-1990 and 1998-1999). After the exclusion of
      patients diagnosed earlier as having hyperthyroidism or hypothyroidism, the mean
      TSH level in the years 1998-1999 was significantly higher as compared to data
      obtained between 1989 and 1990 (1.44 microj/ml vs. 1.30 microj/ml) in the
      examined population. Our 10 years observation revealed an insignificant increase
      in frequency of hyperthyroidism only among females (1.6% vs. 0.9%) which did not
      indicate a clear, endemic in character increase at the population level. In the
      present investigations, hypothyroidism was demonstrated to occur more frequently
      as compared to the 1989-90 study (2.1% vs. 1.4% among females and 0.3% vs. 0% in
      males). Both differences were not statistically significant. As seen from the
      present results, over the investigated 10-year period, in the Cracow population,
      there occurred a clear, statistically significant (p<0.001) increase of the
      percentage of individuals with an elevated TPO antibody titter (3.8% vs. 11.8%).
      In our investigation no correlation was observed between anti-TPO antibodies and
      ioduria levels. CONCLUSIONS: The results reveal no statistically significant
      increase in incidence of hyperthyroidism and hypothyroidism after implementation
      of the obligatory model of iodine prophylaxis. The future studies are needed to
      clarify the mechanisms involved in increase of anti-TPO autoantibodies and verify
      its possible temporary nature.

PMID- 16463702
TI  - [Diagnostic problems with recognition of primary hyperparathyroidism].
AB  - The aim of our study was to compare the results of biochemical and imaging
      investigations with histopathological diagnosis in operated patients with primary
      hyperparathyroidism. 46 subjects were included into the study, pathologically
      demonstrated as parathyroid adenoma--23 subjects, parathyroid hypertrophy--16,
      parathyroid carcinoma--2 and in 5 patients parathyroid gland was not found in
      resected tissue. The most frequent complications of primary hyperparathyroidism
      in our group were osteoporosis (87%) and nephrolithiasis (64.1%). 99mTc-MIBI
      imaging described as a parathyroid adenoma or parathyroid hypertrophy were
      confirmed pathologically in 52 and 57.1%, respectively. Three typical symptoms of
      primary hyperparathyroidism assessed in our study (hypercalcemia, hypercalciuria
      and increased concentration of parathormone) were observed only in about 50%
      patients with histopathological diagnosis of adenoma and hypertrophy. The lowest
      average calcium serum level (2.87 mmol/l), urinary calcium level (7.8 mmol/24h)
      and parathyroid hormone concentration (209.4 pg/ml) were observed in patients
      with parathyroid adenoma, the highest levels of these parameters were noticed in
      patients with parathyroid carcinoma (3.41 mmol/l; 14.6 mmol/24h; 687.8 pg/ml,
      respectively), patients with parathyroid adenoma were characterized by
      intermediate values (2.98 mmol/l; 9.7 mmol/24h; 285.5 pg/ml, respectively). After
      parathyroidectomy lowering in average calcium serum level (2.94 vs. 2.16 mmol/l),
      parathyroid hormone concentration (244.45 vs. 54.15 pg/ml) and increasing in
      average phosphate serum level (0.81 vs. 1.04 mmol/24h) were observed in our
      group. Finally, using different biochemical and imaging investigations is
      necessary for proper recognition of primary hyperparathyroidism due to occurring
      of oligosymptomatic cases.

PMID- 16463703
TI  - [Early diagnosis of renal diseases--preliminary results from the pilot study
      PolNef].
AB  - Continuous increase of the number of patients with chronic kidney failure which
      require renal replacement therapy, in Poland as all as over the world, demands
      the analysis of epidemiological situation concerning renal diseases. Early
      diagnosis of nephropathy permits not only an adequate treatment, but also
      facilitates the introduction of the therapy that slows the progression of kidney
      failure. The aim of the pilot study PolNef was an attempt to evaluate the
      epidemiology of renal diseases in Poland on the basis of a randomly selected
      population from a city numbering 60 thousand people. As a screening test,
      allowing to distinguish patients requiring further diagnostic of nephropathy, the
      microalbuminuria dipstick test accompanied by blood pressure measurement and
      questionnaire was accepted. Microalbuminuria was detected in more than 18% of the
      population investigated up till now. It was more frequent in male, in obese, and
      in smokers. More than 33% of all participants consulted by the nephrologist
      required permanent nephrological care and for the next 32% another nephrological
      consultation in 6 to 12 month should be ordered. Decreased clearance of
      creatinine was found in above 17% participants and 6 patients were referred for
      further treatment because of new diagnosis of renal tumor. Identification in
      investigated population patients with of an early stage of kidney disease needs
      further nephrological diagnosis and treatment is especially important from the
      point of view of every single patient and also may bring substantial economic
      benefits for health protection system as well.

PMID- 16463704
TI  - [Treatment of hypertension in dialysis patients and renal transplant recipients].
AB  - Hypertension is often observed in dialysis patients and renal transplant
      recipients and is a very important risk factor for cardiovascular morbidity and
      mortality. Despite this high prevalence, the treatment of hypertension in these
      populations is poorly characterized. This article describes the current state of
      knowledge in treatment of hypertension in patients on renal replacement therapy.
      It is not appropriate, to limit the choice of drug to a single class of agents
      because people usually have other medical problems that affect this decision.

PMID- 16463706
TI  - [Exogenous and endogenous infections of genital tract].
AB  - The paper is an overview of etiological factors, clinical manifestations,
      diagnostics and treatment of genital tract infections. Infections caused by
      Trichomonas vaginalis, fungi Candida, Saccharomyces and Geotrichum are discussed
      as well as syphilis, gonorrhea and infections with Chlamydia, mycoplasms and
      ureaplasms. The problem of vaginal dysbacteriosis and mixed infections is pointed
      out.

PMID- 16463705
TI  - [Risk factors and development of skin neoplasms in patients after kidney
      transplantation].
AB  - Kidney transplant recipients, comparing to general population, have an increase
      risk of cancer development. The most frequent lesions, observed in this
      population, are skin cancers, especially NMSCs (nonmelanoma skin cancers) which
      make up to 50% of all malignant lesions. The incidence of neoplasm is influenced
      by demographic characteristics and the highest prevalence achieve in Australia
      where 52.5% of kidney recipients develop skin cancer after 10 years after
      transplantation and 82.1% after 20 years. Authors in the following article
      describe the most common cutaneous premalignant and malignant lesions in patients
      after kidney transplantation, types of their treatment, and potential risk factor
      responsible for its development.

PMID- 16463707
TI  - [Intrauterine growth restriction].
AB  - Intrauterine growth restriction (IUGR) is found in 1-10% of all pregnancies, and
      among women with risk factors even twice often. It is connected to worse
      obstetric results, and its complications can arise long time after delivery. In
      the paper we described etiology, diagnostics and monitoring of IUGR and its
      consequences for the child and for the course of neonatal periode.

PMID- 16463708
TI  - [Role of neopterin in clinical diagnostics].
AB  - Neopterin is a low-molecular mass substance synthesized from guanosine
      triphosphate (GTP) in monocytes/macrophages due to IFNgamma stimulation. The
      cellular immune system is involved in or affected by the disease process in
      various conditions such as viral infections (AIDS), autoimmune disorders
      (rheumatoid arthritis, systemic lupus erythematosis, Crohn's disease), malignancy
      and monitoring after solid organ transplants. Similar to procalcitonin, neopterin
      determination can assist in the differential diagnosis between viral and
      bacterial infection and as an indicator for impending septic complications (MODS
      vs. sepsis). Because of fact that reduced glamerular filtration rate neopterin
      accumulates in the blood, neopterin determination in multiorgan failure or sepsis
      patients are limited. The aim of this study was to evaluate the usefulness of
      neopterin in clinical diagnostics.

PMID- 16463709
TI  - [Measurement of airway inflammation in asthma].
AB  - Despite of the tremendous progress, which was made within the last few years in
      the diagnostics and treatment of asthmatic patients, there is a lack in a simple,
      non-invasive methods, which could be useful in the diagnostics and anti
      inflammatory treatment monitoring. Invasive methods, such as bronchofiberoscopy
      (bronchoalveolar lavage fluid analysis and bronchial biopsy), enabled the better
      understanding of the pathophysiology of asthma and the elaboration of the grounds
      of pharmacological treatment of this disease. Unfortunately, these methods are
      less useful in the clinical practice due to their invasiveness. Spirometry, which
      is essential in diagnostics and treatment of asthmatics, is only indirect way of
      the airway inflammation assessment. Recent studies are focused on noninvasive
      methods of the evaluation of airway inflammation, such as measurements of exhaled
      nitric oxide (FENO) and allergic inflammation mediators in the inducible sputum.
      The higher degree of inducible form of nitric oxide synthase (iNOS) expression
      and higher levels of nitric oxide in exhaled air are observed in asthmatic
      patients. Many studies confirm, that the measurement of exhaled nitric oxide is a
      simple, non-invasive method in diagnostics and treatment monitoring in
      asthmatics, which does not intensify the symptoms of asthma.

PMID- 16463711
TI  - [Real activity of Krakow endocrine group in Institute of Pediatrics CMUJ on the
      eradication of IDD in Polish children].
AB  - The authors present the investigations concerned the Iodine deficiency disorders
      (IDD) elimination in children living in South-East of Poland in last 15 years. To
      achieve the full success, what, as we know is possible, the monitoring and the
      exact control of the salt iodine supplementation according to the National
      Program of Iodine Deficiency Elimination (1999-2003) should be maintained. To
      avoid any negligence, the prompt education of the whole population is necessary,
      but yet especially the pregnant women. It is important to instruct them about the
      direct influence of iodine deficiency on the mental development of the fetus and
      the newborn.

PMID- 16463710
TI  - [The beta2-adrenergic receptor agonists in the treatment of chronic obstructive
      pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is considered one of the most common
      chronic diseases in the world. It is characterized by the progressive reduction
      of the respiratory parameters, relatively low effectiveness of recommended
      treatment as well as serious prognosis especially in the group of patients with
      advanced disease. The beta2-adrenergic receptor agonists are first-line
      therapeutics in the treatment of COPD patients. Due to their diverse
      pharmacokinetic characteristic beta2-mimetics are recommended both for regular or
      "rescue" treatment to prevent or to restrain dyspnea symptoms. This paper
      evaluates main differences between the mechanism of action and pharmacokinetic
      profile of the key beta2-mimetics, discusses consequences of those diversities
      for their the clinical application and potential side effects.

PMID- 16463712
TI  - [Late drug-induced hyperkalemia in a patient with congestive heart failure].
AB  - Patients with congestive heart failure are at risk for hiperkaliemia because of
      coexisting comorbidities and use of multiple medications that impair potassium
      excretion--such as angiotensin-converting enzyme inhibitors or spironolactone.
      This is the case report about the patient with late drug-induced hyperkalemia.
      Causes and prevention methods used against development of this adverse event were
      explained.

PMID- 16463714
TI  - The emerging science of energy healing.

PMID- 16463713
TI  - [Severe exacerbation of chronic renal failure in the course of asymptomatic
      cystolithiasis].
AB  - There has been reported a case of severe exacerbation of chronic renal failure
      with bilateral hydronephrosis and urosepsis, which was caused by asymptomatic
      large urinary bladder stone. Life-threatening symptoms of uraemic syndrome were
      found, which required temporary hemodialysis treatment. Following removal of the
      calculus and controlling of severe urinary tract infection the patient was
      discharged with stable blood serum creatinine concentration 3.8 mg/dl.

PMID- 16463715
TI  - Finding Reiki: applications for your nursing practice.

PMID- 16463716
TI  - Cellular memory release: a new modality for depression.

PMID- 16463717
TI  - Intergrating energy healing in new environments and for self-care.

PMID- 16463718
TI  - A true life-saving story.

PMID- 16463719
TI  - Helping clients move forward.

PMID- 16463720
TI  - Electromagnetism and the growth of energy medicine since 1980.

PMID- 16463721
TI  - Introducing AHNA's web-based network for energy practitioners.

PMID- 16463722
TI  - Accuracy and resolution of a dynamic-speckle profilometer.
AB  - We propose and demonstrate a new technique for fast noncontact and continuous
      profile measurement of a rough surface. The technique is based on frequency
      tracking of the power modulation of spatially filtered scattered light. A dynamic
      speckle pattern is created when the laser beam scans the surface under study. The
      main advantage of the proposed technique is high scanning speed, which provides
      an extremely short response time of the distance sensor (<0.1 micros). Parameters
      that affect accuracy and resolution of the system are analyzed. Possible ways for
      further improvement of the measurements accuracy are discussed.

PMID- 16463724
TI  - Correction of detector nonlinearity for the balloonborne Michelson Interferometer
      for Passive Atmospheric Sounding.
AB  - The detectors used in the cryogenic limb-emission sounder MIPAS-B2 (Michelson
      Interferometer for Passive Atmospheric Sounding) show a nonlinear response, which
      leads to radiometric errors in the calibrated spectra if the nonlinearity is not
      taken into account. In the case of emission measurements, the dominant error that
      arises from the nonlinearity is the changing detector responsivity as the
      incident photon load changes. The effect of the distortion of a single
      interferogram can be neglected. A method to characterize the variable
      responsivity and to correct for this effect is proposed. Furthermore, a detailed
      error estimation is presented.

PMID- 16463723
TI  - Recognition of living fingers with a sensor based on scattered-light detection.
AB  - To prevent fraud by use of replicas of human fingers for identity verification,
      we propose to check variations in color and in a series of previously acquired
      fingerprint images. Movement of a finger on a human hand induces blood movement,
      and light scattered inside the finger carries this life-related information. In
      experiments, we found characteristic changes in color and luminance extracted
      from the central parts of fingerprint images. Some criteria for recognition of
      living tissue were tested with input provided by more than 30 participants.
      Inasmuch as the response of a human body to an external stimulus can be checked
      by our method with no additional components, this technology can raise the
      security level of a fingerprint identification system.

PMID- 16463725
TI  - Describing isotropic and anisotropic out-of-plane deformations in thin cubic
      materials by use of Zernike polynomials.
AB  - Isotropic and anisotropic out-of-plane deformations induced by thin-film residual
      stress on thin cubic materials are studied. By transforming the compliance
      tensor, an analytical expression can be derived for the biaxial stiffness modulus
      for all directions in any given cubic crystal plane. A modified Stoney's
      equation, including both isotropic and anisotropic terms, can be formulated to
      predict the anisotropic out-of-plane deformation. The isotropic and anisotropic
      deformations are then described using the Zernike polynomials U21 and U22,
      respectively. Experimental results from (100) and (110) silicon wafers confirm
      the model by quantitatively comparing the changes in Z21 and Z22 coefficients due
      to thin-film stress.

PMID- 16463726
TI  - One more possible mechanism of Weigert's effect in azo-dye-colored materials.
AB  - One of the purposes of investigating the mechanisms of Weigert's effect in azo
      dye-colored materials is the search for ways to improve their corresponding
      characteristics. So far the suggested mechanisms based on the isomerization
      process of the molecules of the dyes do not account for some facts that take
      place in this case. I present some results of the investigation of Weigert's
      effect in azo-dye-colored materials and propose a possible new mechanism.

PMID- 16463728
TI  - Digital holographic microscopy with dual-wavelength phase unwrapping.
AB  - We apply the techniques of digital holography to obtain microscopic three
      dimensional images of biological cells. The optical system is capable of
      microscopic holography with diffraction-limited resolution by projecting a
      magnified image of a microscopic hologram plane onto a CCD plane. Two-wavelength
      phase-imaging digital holography is applied to produce unwrapped phase images of
      biological cells. The method of three-wavelength phase imaging is proposed to
      extend the axial range and reduce the effect of phase noise. These results
      demonstrate the effectiveness of digital holography in high-resolution biological
      microscopy.

PMID- 16463727
TI  - Proteins and dipicolinic acid released during heat shock activation of Bacillus
      subtilis spores probed by optical spectroscopy.
AB  - UV fluorescence and absorption spectroscopy from Bacillus subtilis spores
      detected proteins and dipicolinic acid (DPA) released into the supernatant after
      heat treatments ranging from 20 degrees to 90 degrees C. The protein and DPA
      concentration in the supernatant was greater with higher heat treatment
      temperatures, undergoing a substantial increase for T > or = 60 degrees C, and
      supporting the theory that spores undergo a phase transition from a glassylike to
      a rubberylike state at 56 degrees C. Gel electrophoresis detected several small
      proteins with molecular weights between 6 and 11 kDa. These proteins may be small
      acid-soluble spore proteins that are present in spores but break down during
      germination. A 30 kDa protein extracted above 60 degrees C is related to the
      rubber-glass phase transition.

PMID- 16463729
TI  - Orientation-independent differential interference contrast microscopy.
AB  - We describe a new technique for differential interference contrast (DIC)
      microscopy, which digitally generates phase gradient images independently of
      gradient orientation. To prove the principle we investigated specimens recorded
      at different orientations on a microscope equipped with a precision rotating
      stage and using regular DIC optics. The digitally generated images successfully
      displayed and measured phase gradients, independently of gradient orientation.
      One could also generate images showing distribution of optical path differences
      or enhanced, regular DIC images with any shear direction. Using special DIC
      prisms, one can switch the bias and shear directions rapidly without mechanically
      rotating the specimen or the prisms and orientation-independent DIC images are
      obtained in a fraction of a second.

PMID- 16463730
TI  - Dark-field imaging with cylindrical-vector beams.
AB  - Dark-field illumination provides an imaging mode that rejects specular light,
      thereby highlighting edge features. We analyze dark-field imaging by using
      cylindrical vector beam illumination with a confocal microscope equipped with a
      microstructure fiber mode filter. A numerical model based on rigorous coupled
      wave analysis has been used to analyze the method. We acquired images of
      separated edges features to investigate the edge separation resolution of the
      method. A through-focus comparison of azimuthal and radial polarization shows a
      measurable dependence of edge separation on polarization.

PMID- 16463731
TI  - Fabrication of three-dimensional photonic crystals with two-beam holographic
      lithography.
AB  - A holographic technique used to fabricate three-dimensional photonic crystals
      with a two-beam interference method is presented. In the optical setup of
      fabrication one beam is incident on the recording plate in the direction of the
      plate normal and the other beam with an angle to the normal. Three exposures were
      taken. Between each exposure, the recording plate was rotated 120 degrees on axis
      until three exposures were completed. Good three-dimensional lattice structures
      have been obtained. Theoretical analysis, computer simulations, and experimental
      results are presented.

PMID- 16463732
TI  - Linear astigmatism of confocal off-axis reflective imaging systems and its
      elimination.
AB  - Linear astigmatism of a confocal off-axis reflective imaging system when the
      object plane is tilted and located at a finite distance from the imaging system
      is derived. We show that linear astigmatism can be eliminated by proper
      configuration of the parent mirror axes in confocal off-axis two-mirror systems.
      The tilt angle of the image plane is also derived. The developed theory is
      verified by ray-tracing analysis of an example system.

PMID- 16463734
TI  - Dichroic rugate filters.
AB  - We reduce the sidelobes that are present in the bandpass zones of rugate filters,
      using antireflection coatings to design dichroic rugate filters. Our designs are
      based on the formalism of equivalent systems that allow us to consider a rugate
      filter a simple equivalent layer with equivalent optical admittance and
      equivalent phase thickness functions. Rugate filters with apodization were
      considered.

PMID- 16463733
TI  - Correction method for absorption-dependent signal enhancement by a liquid-core
      optical fiber.
AB  - The enhancement of a dissolved chemical's Raman scattering by a liquid-core
      optical fiber (LCOF) geometry is absorption dependent. This dependence leads to a
      disruption of the usual linear correlation between chemical concentration and
      Raman peak area. To recover the linearity, we augmented a standard LCOF Raman
      spectroscopy system with spectrophotometric capabilities, permitting sequential
      measurements of Raman and absorption spectra within the LCOF. Measurements of
      samples with identical Raman-scatterer concentrations but different absorption
      coefficients are described. Using the absorption values, we reduced variations in
      the measured Raman intensities from 60% to less than 1%. This correction method
      should be important for LCOF-based Raman spectroscopy of sample sets with
      variable absorption coefficients, such as urine and blood serum from multiple
      patients.

PMID- 16463735
TI  - Synthetic-aperture chirp confocal imaging.
AB  - An imaging system that combines synthetic-aperture imaging, holography, and an
      optical chirp with confocal imaging is described and analyzed. Comparisons are
      made with synthetic-aperture radar systems. Adaptation of several synthetic
      aperture radar techniques to the optical counterparts is suggested.

PMID- 16463736
TI  - High-power and high-accuracy integrating sphere radiometer: design,
      characterization, and calibration.
AB  - We describe the design, characterization, and calibration of a high-power and
      high-accuracy transfer standard for optical power measurements in fibers based on
      an integrating sphere radiometer working from -50 to +30 dBm. The integrating
      sphere radiometer has been calibrated in the spectral range 1250-1650 nm by use
      of an electrically calibrated pyroelectric radiometer and four tunable laser
      diodes. The total uncertainty obtained is less than +/-0.8% for these wavelength
      and power ranges.

PMID- 16463737
TI  - Origin of spectral modal noise in fiber-coupled spectrographs.
AB  - We describe the origin of spectral modal noise in a fiber-coupled spectrograph.
      Prior investigations of this phenomenon have considered optical fibers with large
      cores that support thousands of optical modes and used a statistical treatment to
      analyze spectral noise that arises from interference between the modes. We
      examine spectral modal noise for a fiber-coupled spectrograph with a smaller
      diameter fiber core, optimized for adaptively corrected telescopes, that supports
      only a few propagating modes for visible and near-infrared light. Simulations to
      predict the minimum amount of fiber stretch required to shift spectral
      oscillations by a half-period are confirmed by experiment.

PMID- 16463738
TI  - Development of a parallel demodulation system used for extrinsic Fabry-Perot
      interferometer and fiber Bragg grating sensors.
AB  - A parallel demodulation system for extrinsic Fabry-Perot interferometer (EFPI)
      and fiber Bragg grating (FBG) sensors is presented, which is based on a Michelson
      interferometer and combines the methods of low-coherence interference and a
      Fourier-transform spectrum. The parallel demodulation theory is modeled with
      Fourier-transform spectrum technology, and a signal separation method with an
      EFPI and FBG is proposed. The design of an optical path difference scanning and
      sampling method without a reference light is described. Experiments show that the
      parallel demodulation system has good spectrum demodulation and low-coherence
      interference demodulation performance. It can realize simultaneous strain and
      temperature measurements while keeping the whole system configuration less
      complex.

PMID- 16463739
TI  - Holmium lasers passively Q-switched with PbS quantum-dot-doped glasses.
AB  - PbS quantum-dot-doped glasses are demonstrated as saturable absorber Q-switches
      for 2 microm holmium lasers. Q-switched pulses from Ho3+:Y3Sc2Al3O12 and
      Ho3+:Y3Al5O12 lasers of 50 and 70 ns in duration, respectively, have been
      obtained demonstrating up to 13% of energy conversion efficiency from free
      running to Q-switched output.

PMID- 16463740
TI  - Duty cycle dependence of a periodically poled LiNbO3-based electro-optic Solc
      filter.
AB  - We demonstrate that the performance of a periodically poled LiNbO3- (PPLN-) based
      electro-optic Solc filter is dependent on the duty cycle of the crystal. This may
      limit the performance of the device for applications such as add-drop filtering
      and switching, owing to the deterioration of the extinction ratio. It is shown
      that by adding a retarder to the Solc filter it is possible to improve the
      extinction ratio; thus the dependence of the filter on the duty cycle can be
      reduced. Using Jones calculus, we analyzed the effect of a variable retarder that
      can also be rotated on the extinction ratio. We experimentally observed a 6 dB
      increase in the extinction ratio when we used a half-wavelength retarder.

PMID- 16463741
TI  - Matrix form for the instrument line shape of Fourier-transform spectrometers
      yielding a fast integration algorithm to theoretical spectra.
AB  - The instrument line shape (ILS) of a Fourier-transform spectrometer is expressed
      in a matrix form. For all line shape effects that scale with wavenumber, the ILS
      matrix is shown to be transposed in the spectral and interferogram domains. The
      novel representation of the ILS matrix in the interferogram domain yields an
      insightful physical interpretation of the underlying process producing self
      apodization. Working in the interferogram domain circumvents the problem of
      taking into account the effects of finite optical path difference and permits a
      proper discretization of the equations. A fast algorithm in O(N log2 N), based on
      the fractional Fourier transform, is introduced that permits the application of a
      constant resolving power line shape to theoretical spectra or forward models. The
      ILS integration formalism is validated with experimental data.

PMID- 16463742
TI  - Tunable ultrafast infrared/visible laser to probe vibrational dynamics.
AB  - A tunable, ultrafast (approximately 100 fs-approximately 1 ps) laser system
      generating mid-IR (3-10 microm) and UV/visible (392-417 nm, 785-835 nm) radiation
      is described and its output characterized. The system is designed to explore
      vibrational dynamics in the condensed phase in a direct, two-pulse, time-resolved
      manner, using Raman spectroscopy as the probe. To produce vibrational resolution,
      probe pulses are spectrally narrowed by use of a long doubling crystal. Frequency
      resolved optical gating is used to evaluate beam characteristics. An effective
      method for determining the temporal overlap of the pump and probe pulses for a
      one-color, 400 nm configuration is illustrated. Representative results from
      studies of heme and paranitroaniline vibrational dynamics illustrate the
      effectiveness of the visible pump-visible probe portion of the system in
      illuminating fast structure and energy dynamics.

PMID- 16463743
TI  - Degenerated optical parametric chirped-pulse amplification with cesium lithium
      borate.
AB  - A gain amplifier for degenerated optical parametric chirped-pulse amplification
      (OPCPA) with lithium triborate and cesium lithium borate (CLBO) crystals was
      demonstrated in a near-collinear configuration. The signal gain of the final
      energy amplifier with CLBO was approximately 6. After compression, the 123 fs
      pulse duration was obtained. Compared with potassium dihydrogen phosphate, it is
      confirmed that CLBO is more effective as a nonlinear crystal in a final power
      amplifier for terawatt or petawatt OPCPA systems. To our knowledge, this is the
      first demonstration of OPCPA with CLBO.

PMID- 16463744
TI  - Monte Carlo study of the screening effect of carriers on terahertz radiation from
      InAs with high excitation intensity.
AB  - The dynamics of terahertz radiation from InAs were investigated by the ensemble
      Monte Carlo simulation method. Our simulations indicated that under high
      intensity excitation it is the ratio of carrier screening to the carrier-polar
      optical phonon scattering that has an obvious influence in high-frequency
      components of terahertz pulses; that is, the amplitudes of high-frequency spectra
      are reduced with increased excitation intensity. Our calculated results
      qualitatively reproduce recently published experimental data.

PMID- 16463745
TI  - Focusing multiple high-order harmonics in the extreme-ultraviolet and soft-x-ray
      regions by a platinum-coated ellipsoidal mirror.
AB  - The focusability of multiple high-order harmonics in the extreme-ultraviolet and
      soft-x-ray regions is described, together with the design and performance of the
      ellipsoidal mirror used for this purpose. The mirror focuses intense coherent
      light in the spectral-region from 25 to 40 nm into a 2.4 microm spot size with a
      focused peak intensity of 6 x 10(13) W/cm2. The focal images indicate that a good
      beam profile is obtained with a near-Gaussian distribution and a beam quality
      factor (M2 value) as low as 2.4.

PMID- 16463746
TI  - Newborn survival revolution.

PMID- 16463747
TI  - Quality of health care and its effects in the utilisation of maternal and child
      health services in Kenya.
AB  - OBJECTIVE: To assess the quality of care provided by the Kisumu Municipal health
      facilities, with special reference to Maternal and Child health services (MCH).
      DESIGN: A descriptive cross-sectional survey. SETTING: Kisumu Municipal Health
      facilities. SUBJECTS: Four hundred and eighty two mothers were interviewed in a
      household survey. RESULTS: A total of 482 mothers were interviewed in the
      household survey. Out of these, only 40.4%, 53.7% and 45.7% had respectively used
      Municipal facilities for antenatal services (ANC), immunisation and treatment of
      their children the last time they required such a service. This translates to by
      pass rates for Municipal health facilities of 59.5%, 46.3% and 54.3% respectively
      for the three services. By-pass was higher for the more central urban catchment
      areas than the more peripheral ones, a finding that was associated with the socio
      economic status of the respondents and the relative location of the municipal
      facilities vis-a-vis competing facilities, mainly the District and Provincial
      hospitals. The main reasons cited for by-pass were poor care (21%), lack of drugs
      and supplies (17%) and lack of/poor laboratory services (12%). From the facility
      audit, most of the clinics had a reasonable capacity to offer basic health care
      with only three scoring less than 50% in the scale used. The worst areas were in
      availability of drugs, equipment and management issues. There was a strong
      relationship between the perceived quality of care and utilisation of MCH
      services as well as by-pass. The capacity of the facilities to offer care was
      however not associated with utilisation of MCH services or by-pass. CONCLUSION:
      There is under-utilisation of Municipal health facilities for MCH services. This
      is related to the perceived poor quality of care in the facilities. Perception of
      quality is influenced by a person's socio-economic status especially education.

PMID- 16463748
TI  - Factors predisposing to low birth weight in Jimma Hospital south western
      Ethiopia.
AB  - BACKGROUND: Low birth weight continues to remain a major public health problem in
      Ethiopia in contrast to what is observed in many developing countries.
      OBJECTIVES: To assess some of the predisposing factors to low birth weight among
      deliveries in Jimma hospital. DESIGN: Cross-sectional case referent study.
      SETTING: Maternal and child health clinic and maternity ward of Jimma University
      Hospital, Ethiopia. SUBJECTS: One hundred and forty seven mothers who gave birth
      to low birth weight (LBW) babies between June 1999 and July 2000 were identified.
      MAIN OUTCOME MEASURES: Normal and low birth weight. RESULTS: The incidence of LBW
      was found to be 11.02%. Mothers younger than 20 years and > or =35 years, short
      stature (< or =150 cm), late first antenatal visit and complications during
      pregnancy were significantly associated with LBW (p<0.001). However, parity
      showed a negative association with LBW. CONCLUSION: Attention to nutritional
      education, early antenatal care interventions and strengthening of maternal and
      child health assists in combating LBW in the area.

PMID- 16463749
TI  - Epidemiology of intestinal nematodes in school-age children of the Kumba Urban
      Area, south west Cameroon.
AB  - BACKGROUND: The urban slums, poorly disposed garbage and inadequate toilet
      facilities in many homes, coupled with the high temperatures, rainfall and
      humidity that characterise the Kumba urban area, favour the development and
      transmission of helminth parasites in the area. School-age children are
      particularly at risk of infection. OBJECTIVE: To determine the pattern of soil
      transmitted nematode infections in the Kumba urban area as affected by seasonal
      changes. DESIGN: Longitudinal study. SETTING: Ten primary schools in the Kumba
      urban area. SUBJECTS: Five hundred and eighty seven randomly selected pupils aged
      between four and fifteen years of both sexes. RESULTS: Significantly (P<0.005)
      more children were infected towards the end (69%) than in the early months
      (38.3%) of the rainy season. The infection rate recorded in December/January (dry
      season) was significantly reduced in April/May (early months of the rainy season)
      in male and female (P<0.01) children of different age groups (P<0.005) and
      classes (P<0.05). Then after, the rate increased significantly (P<0.005) in all
      the groups to reach a peak in October/November (last months of the rainy season).
      The intensity of infection more or less followed the same pattern as prevalence,
      except in hookworms where prevalence increased progressively and significantly
      (P>0.05) from 10.7% in December/January to 19.4% in October/November, while the
      worm load decreased. Single and mixed species infections constituted 50.8% and
      49.2% respectively of the infections investigated, with Ascaris lumbricoides
      accounting for the highest number of infections. The most common combination of
      mixed species infections was Ascaris/Trichuris. CONCLUSION: The study has
      revealed that, in general, progressively more school-age children are infected
      with soil-transmitted nematodes in the course of the rainy season while
      acquisition of infections in the dry season progressively reduce to the low
      levels observed in the early months of the rainy season.

PMID- 16463750
TI  - Analysis of cost and effectiveness of pre-transfusion screening of donor blood
      and anti-malarial prophylaxis for recipients.
AB  - OBJECTIVES: To determine the prevalence of malaria in donor units in a low and a
      high endemic region in Kenya and evaluate the cost effectiveness of recipient
      anti-malarial prophylaxis and pre-transfusion screening (using an automated
      method) as options to prevent post transfusion malaria. DESIGN: A descriptive
      cross-sectional study. SETTING: Two regional blood banks, Nairobi and its
      environs (National Blood Transfusion Services, Nairobi) a low malaria endemic
      region and western region (National Blood Transfusion Services, Kisumu) high
      malaria endemic region. SUBJECTS: All the donated units were included in the
      study for analysis, during the duration of study, from the two study sites. MAIN
      OUTCOME MEASURES: Prevalence of malaria in donor units in low endemic area
      (Nairobi) and high endemic area (Kisumu). Cost per case prevented for the two
      options, Option I Prophylactic administration of anti-malarial (sulfadoxine
      pyrimethamine SP) drugs to recipients, and Option II pre-transfusion screening
      using an automated technique. RESULTS: A malaria prevalence of 0.67% was found in
      Nairobi and its environments (low endemic) and 8.63% for Kisumu and its
      environments (high endemic area). The cost analysis showed a cost per case
      prevented of Ksh.105 (US$1.4) adult, Ksh.52.5 (US$0. 69) and paediatric for the
      option of recipient prophylaxis using an SP based drug. The cost escalated to
      Ksh.592 (US$7.79) adult Ksh.444 (US$5.84) paediatric if the prophylaxis was
      upgraded to the recommended artemisinin derivative (ACT-artemisinin based
      combination) and for the option of pre-transfusion screening using an automated
      technique the cost was Ksh.2.08 (US$0.03). CONCLUSION: The prevalence of malaria
      in donors showed the expected regional variation in the low and high endemic
      areas and was comparable to data obtained elsewhere. If malaria positive donor
      units were to be excluded from the national blood supply, an estimated 5%
      (compared to 1.3% for human Immunodeficiency virus, 3.6% for hepatitis B virus
      and 1.3% for hepatitis C virus) would be wasted. The cost per case prevented of
      transfusion-associated malaria is considerably higher for recipient antimalarial
      prophylaxis than pre-transfusion screening using an automated technique. The cost
      escalates by five to seven times if the newer artemesinin based combination
      antimalarial drugs are adopted.

PMID- 16463751
TI  - Dietary habits, plasma polyunsaturated fatty acids and selected coronary disease
      risk factors in Tanzania.
AB  - OBJECTIVES: To compare dietary habits and percent compositions of omega (omega)-3
      fatty acid (FA) in plasma phospholipids and to examine if there is any
      association between fish intake and selected coronary disease risk (CHD) factors
      in this population. DESIGN: Cross sectional population study. SETTING: Three
      areas in Tanzania: urban Dar es Salaam (D), rural Handeni (H) and pastoralist
      population of Maasai in Moduli (Mo). SUBJECTS: One hundred and five participants
      (Dar 36, Handeni 37 and Monduli 32) aged 47-57 years. MAIN OUTCOME MEASURES:
      Fatty acids composition in plasma phospholipids. RESULTS: The frequency of intake
      of fish, meat, coconut milk and fruits was higher in Dar than in Handeni or
      Monduli (all p< 0.0001). The Maasai from Monduli had the highest percentage
      consumption of milk in a week (p<0.0001) and lowest intake of fish (p<0.0001).
      Participants from Handeni had the highest prevalence of consumption of green
      vegetables (p<0.0001). Percent compositions of arachidonic acid (AA; C20: 4omega
      6) and docosahexaenoic acid (DHA; C22: 6omega-3) in plasma phospholipids were the
      lowest in Monduli (p<0.0001). Selected coronary disease risk factors were higher
      in the urban area Dar. The frequency of intake of fish per week correlated
      negatively with total cholesterol (TC) and LDL-C and HBA1c percent but not with
      blood pressure. The percent composition of omega-3 FA in plasma phospholipids was
      positively correlated with the frequency of intake of fish a week. CONCLUSION:
      Our results indicate that, there are significant differences in dietary patterns
      among the three study areas, and that the intake of fish is inversely associated
      with selected risk factors for coronary heart disease.

PMID- 16463752
TI  - Reasons, methods used and decision-making for pregnancy termination among
      adolescents and older women in Mulago Hospital, Uganda.
AB  - OBJECTIVE: To explore the methods, reasons and decision-making process for
      termination of pregnancy among adolescents and older women, in Mulago hospital,
      Kampala, Uganda. DESIGN: Comparative study. SUBJECTS: Nine hundred and forty two
      women seeking postabortion care, of which 333 had induced abortion (of whom 115
      were adolescents). SETTING: The emergency gynaecological ward of Mulago Hospital,
      Kampala, Uganda from September 2003 through June 2004. RESULTS: Women with
      induced abortion were single, in polygamous marital relationships and of lower
      parity (p<0.001); had lower education and number of living children (p<0.05),
      reported more (p<0.001) mistimed, unplanned or unwanted pregnancies, and were 13
      times more likely to have recent history of domestic violence. Relationship
      issues were the most common reason for pregnancy termination for both categories.
      Decision-making for induced abortion was influenced by socio-economic,
      educational and personal considerations. Instrumentation and use of local herbs
      in the genitalia were the most common methods for pregnancy termination. Neither
      methods used for pregnancy termination nor reasons differed when adolescents were
      compared with older women. CONCLUSION: Relationship issues influence the decision
      making process for pregnancy termination. Neither methods used for pregnancy
      termination nor reasons for pregnancy termination differ when adolescents are
      compared with older women.

PMID- 16463753
TI  - Prevalence and intensity of Schistosomiasis mansoni in irrigation and non
      irrigation areas of central Kenya.
AB  - OBJECTIVE: To compare the extent of intestinal schistosomiasis among school
      children attending school in an irrigation and non-irrigation area of Central
      Kenya. DESIGN: A cross sectional study. SETTING: Three separate parasitological
      surveys involving four primary schools in Mwea irrigation scheme, Kirinyaga
      District and two from a non-irrigation area in Machakos District. SUBJECTS: One
      thousand two hundred and twenty two children aged between five and nineteen years
      were examined for Schistostoma mansoni infection by Kato thick smear technique.
      RESULTS: High prevelances ranging from 73% to 94% were noted among children in
      all the participating schools. Overall 41% of the infected children had heavy
      infection (>400 eggs per gram), 27% had moderate infection (101-400 epg) and 32%
      had light infection (10-100epg). When data from the two areas were analysed
      seperately, peak eggs output were found in 5-9 year olds among children in
      Kirinyaga while this situation shifted to the 10-14 year olds in Machakos
      children. In Kirinyaga District, boys in the 10-14 years age group had a
      significantly higher output than girls (P<0.01), but this situation was reversed
      in the older children (P<0.05). Girls in Machakos District had consistently but
      non-significantly higher output than boys. CONCLUSION: Intestinal schistomiasis
      is more prevalent and with a higher intensity in the irrigated than in non
      irrigated areas. There were also pronounced age and gender related differences in
      the pattern of infection between the two study areas.

PMID- 16463754
TI  - Dental injuries in 0-15 year olds at the Kenyatta National Hospital, Nairobi.
AB  - OBJECTIVE: To determine the pattern of occurrence of dental injuries in the 0-15
      year-olds. DESIGN: A retrospective study. SETTING: Kenyatta National Hospital,
      Nairobi. SUBJECTS: Five hundred and five patient records with dental injuries
      were retrieved and analysed. RESULTS: A total of 505 patient records with dental
      injuries were retrieved and analysed. Most of the injuries were recorded in the
      year 1999 (22.2%). Boys were more affected (63.0%) than girls (37.0%). The main
      presenting complaint recorded was pain (75.8%). The majority of the patients
      (69.5%) presented for treatment during the same day or the day after trauma.
      Falls were the leading cause of injuries (73.5%). Most injuries involved two
      teeth (47.1%) and the maxillary central incisors were the most affected teeth
      both in the primary (67.5%) and permanent (64.0%) dentitions. Luxation injuries
      were the most common type of dental trauma with 47.5% occurring in the permanent
      teeth and 77.3% in the primary teeth. The main radiographic investigation
      performed was intraoral periapical views (52.9%) following which dental
      extraction (34.4%) was the main treatment modality offered. CONCLUSION:
      Prospective cross-sectional studies to determine the prevalence of dental
      injuries are needed. Furthermore improving the knowledge of dental practitioners
      through continuing dental education programmes would help in updating them on
      current trends in managing these injuries.

PMID- 16463755
TI  - Ceftriaxone or HIV associated angio-oedema? Case report.
AB  - Angio-oedema may be hereditary or acquired and is characterised by episodes of
      potentially life threatening localised tissue oedema and swelling resulting from
      deficiency of compliment pathway C1 esterase inhibitor. Acquired angio-oedema is
      about ten times less frequent than the hereditary type and has been associated
      with immune-deficiency disorders, malignancies and exposure to specific
      medications and food substances. We present a case of seven year old, human
      immune-deficiency virus positive girl, who developed gross swelling of the tongue
      and neck while on treatment for pneumococcal meningitis with ceftriaxone.
      Difficulties in arriving at a definitive diagnosis of angio-oedema in a resource
      poor country are discussed and alternative diagnostic options proposed.

PMID- 16463756
TI  - A randomized controlled trial testing the impact of a support/work-planning
      intervention on first-time parents' health, partner relationship, and work
      responsibilities.
AB  - The authors randomly assigned 151 couples expecting their first child to a
      support/work-planning intervention group or a standard prenatal curriculum group.
      To evaluate the impact of the intervention, they conducted surveys at baseline
      and 6-months postpartum to assess mental and physical health, partner
      satisfaction and caring, work time, housework sharing, and satisfaction with
      housework sharing. They found no significant group differences on postpartum
      health or work outcomes, although fathers in the experimental group, in contrast
      to controls, showed a trend toward less postpartum decline in housework sharing.
      The study identified a tool to help parents plan their postpartum work
      responsibilities. The tool, as tested in this trial, did not have a significant
      impact on parents' work behaviors or health outcomes. Further studies are needed
      to investigate mechanisms to support young parents during their demanding early
      childbearing years.

PMID- 16463757
TI  - Caregiver's distress is associated with delusions in Alzheimer's patients.
AB  - Behavioral disturbances in Alzheimer's (AD) patients might be caused by
      environmental factors. The authors tested the hypothesis that delusions in AD
      might be a result of caregiver's distress. Participants were 22 delusional and 21
      nondelusional mild AD patients and their caregivers. Those who cared for
      nondelusional patients, compared with the delusional patients' caregivers,
      reported higher levels of distress because of behavioral disturbances other than
      delusions. When patients were stratified into 2 groups according to median
      distress value, 64% of the delusional patients and 33% of the nondelusional
      patients showed a high level of caregiver's distress, chi2(1, N = 43) = 3.94, p =
      .047. Although final conclusions about the causal direction of the association
      cannot be drawn, these findings are consistent with the hypothesis that
      distressed caregivers might use inappropriate coping strategies that, in turn,
      might favor the development of delusions.

PMID- 16463758
TI  - Incidence of chaotic eating behaviors in binge-eating disorder: contributing
      factors.
AB  - Because dieting is not as common in patients with binge-eating disorder (BED) as
      among patients with bulimia or anorexia nervosa, the authors assessed the
      incidence, frequency, and contributing factors of semistarvation-like eating
      patterns in BED patients in this study, the first to explore such behaviors in a
      clinical population. They administered the Semistarvation-Associated Behaviors
      Scale (SSABS) to 54 women seeking BED treatment and to 29 controls. The aberrant
      eating behaviors among BED clients were associated with current dieting and
      certain BED criteria, (p < .05). The strongest contributor to chaotic eating
      patterns was negative affect preceding BED (r = .45, p < .001). This finding
      highlights the behavioral psychopathology of BED and strengthens the role of
      negative affect in precipitating binge episodes associated with the disorder.
      These behaviors may help maintain BED by creating a binge-negative affect cycle.
      The SSABS is a tool that may help break this cycle.

PMID- 16463759
TI  - Psychosocial stress and cardiovascular disease Part 2: effectiveness of the
      Transcendental Meditation program in treatment and prevention.
AB  - Psychosocial stress is a nontraditional risk factor for cardiovascular morbidity
      and mortality that may respond to behavioral or psychosocial interventions. To
      date, studies applying such interventions have reported a wide range of success
      rates in treatment or prevention of cardiovascular disease (CVD). The authors
      focus on a natural medicine approach that research indicates reduces both
      psychosocial and traditional risk factors for cardiovascular disease-the
      Transcendental Meditation (TM) program. Randomized controlled trials, meta
      analyses, and other controlled studies indicate this meditation technique reduces
      risk factors and can slow or reverse the progression of pathophysiological
      changes underlying cardiovascular disease. Studies with this technique have
      revealed reductions in blood pressure, carotid artery intima-media thickness,
      myocardial ischemia, left ventricular hypertrophy, mortality, and other relevant
      outcomes. The magnitudes of these effects compare favorably with those of
      conventional interventions for secondary prevention.

PMID- 16463760
TI  - [Clinical classification and treatment of localized attic cholesteatoma].
AB  - OBJECTIVE: To investigate the clinical classification and treatment of localized
      attic cholesteatoma through surgical management. METHOD: Twenty-one patients (21
      ears) of localized attic cholesteatoma accepted atticotomy. Then different
      surgical managements were carried out according to the extent of cholesteatoma
      and whether the malleo-incudal joint was destroyed or not. If the cholesteatoma
      has only reached the surface of the malleo-incudal joint, it was regarded as type
      I (5 patients). To this type, the cholesteatoma was removed and the ossicular
      chain was preserved. If the cholesteatoma has entered the anterior attic space
      and destroyed the malleo-incudal joint, it was regarded as type II (16 patients).
      Besides the removing of cholesteatoma, the head of malleus and incus should be
      removed also in this condition. Then reconstruction of the ossicular chain was
      performed by putting PORP artificial auditory ossicles between the manubrium
      mallei and staple. In all these 21 patients, the lateral wall of attic was
      reconstructed with the cartilage of tragus. The perichondrium of the cartilage
      was used to repair the perforation in the non-vibrant membrane. Healing of the
      lateral wall of attic and the tympanic membrane and recovery of hearing level
      were investigated after the operation. RESULT: The follow-up period lasted 1 year
      to 5 years. Healing of the lateral wall of attic and the tympanic membrane were
      satisfying in all 21 patients. According to the pure tone audiometry after the
      operation, A-B gap was less than 10 decibel in 10 patients,less than 20 decibel
      in 7 patients, less than 30 decibel in 3 patients, and over 30 decibel in only 1
      patient. Acoustic transmission function was preserved or reconstructed. No
      vertigo or tinnitus happened after operation. CONCLUSION: Diagnosis of localized
      attic cholesteatoma should be made early. If it can be treated by clinical
      classification properly, not only the removing of cholesteatoma, but also the
      reservation and recovery of acoustic transmission function can be obtained. It is
      worthy of further discussion.

PMID- 16463761
TI  - [Vestibular evoked myogenic potentials in normal young people].
AB  - OBJECTIVE: To observe the positive rate and other variances of the vestibular
      evoked myogenic potentials (VEMP)in normal young people. METHOD: Fifty-two normal
      young people aged from 21-22 years old including 31 males and 21 females were
      investigated. Intense clicks were given to one test ear and EMG was recorded from
      ipsilateral side. RESULT: VEMPs were presented in both ears in 47 subjects,
      absent in either of the two ears in 5 subjects. Variances averaged from all 94
      positive ears were as follows (mean +/- standard deviation): latencies for p1
      (15.97 +/- 3.22) ms, latencies for n2 (24.41+/- 2.46) ms, interval time between
      p1 and n2 (8.41 +/- 2.06) ms, amplitude (33.27 +/- 14.37) microV, threshold
      (93.67 +/- 5.20) dB nHL. Inter-subject variances averaged from 47 normal subjects
      were as follows:latencies for p1 (0.97 +/- 1.31) ms, latencies for n2 (1.23 +/-
      1.30) ms, interval time between p1 and n2 (0.95 +/- 1.21) ms, amplitude (10.04 +/
      11.88) microV, threshold (2.29 +/- 2.56) dB nHL. There were no significant
      difference between males and females. CONCLUSION: VEMP can be recorded in most
      normal subjects. VEMP may travel along the hypothesized response pathway from the
      vestibular sacculus to the inferior vestibular nerve, vestibular nucleus, and
      lateral vestibulospinal tract to the SCM muscle. VEMP recording could become an
      attractive method for testing otolithic receptors and vestibulospinal pathways.

PMID- 16463762
TI  - [Relationship between adenoids hypertrophy and tympanogram/eustachian tube
      function in children].
AB  - OBJECTIVE: To evaluate the correlation between adenoidal-nasopharyngeal ratio (AN
      ratio) and tympanogram/eustachian tube function in children. METHOD: A
      prospective clinical study from February 2004 to October 2004 was carried out. A
      total of 120 children with adenoids hypertrophy and 20 normal children were
      examined. The relationship between AN ratio and middle-ear pressure was
      evaluated, the eustachian tube function was compared between the children with
      adenoids hypertrophy and the normal. RESULT: (1) Middle ear pressures were
      negative related to the AN ratio (r = -0.41, P < 0.05); (2) the eustachian tube
      function of the children with adenoids hypertrophy was worse than the normal; (3)
      the relation between the eustachian tube function and the AN ratio was not
      statistical difference. CONCLUSION: Eustachian tube dysfunction caused by
      adenoids hypertrophy is the etiologic factor of secretory otitis media.

PMID- 16463763
TI  - [Auditory brainstem implantation in patient with bilateral acoustic neuromas].
AB  - OBJECTIVE: To restore auditory sensation for patient suffering loss of hearing
      due to bilateral acoustic neuromas. METHOD: One patient of bilateral acoustic
      neuromas received auditory brainstem implant (ABI) at the same surgery for
      resection of the second tumor. The retrosigmoid approach was used for resection
      of the tumor and to exposure the lateral recess of the fourth ventricle for
      placement of ABI electrode array. Intraoperative 7th and 9th nerves monitoring
      and electrically evoked auditory brainstem responses (EABR) were recorded to
      localize the placement of ABI electrode array. RESULT: Initial ABI switch-on was
      performed eight weeks after the surgery under close monitoring of vital signs.
      Auditory sensation was perceived on stimulation of all channels. CONCLUSION: The
      multichannel ABI could effectively restore auditory sensation for patient
      deafened by bilateral acoustic neuromas. The accurate location of the cochlear
      complex during surgery was the critical factor for success of ABI.

PMID- 16463764
TI  - [The thresholds comparison of auditory steady-state responses and auditory brain
      stem response].
AB  - OBJECTIVE: To compare the thresholds of auditory brainstem response (ABR)and
      auditory steady-state responses (ASSR) in the same group of deaf children and
      give a clinical evaluation for ASSR after that. METHOD: Both kinds of thresholds
      have been recorded and analyzed of these deaf children. RESULT: The ABR
      thresholds are (85.82 +/- 12.39) and (82.70 +/- 14.93) dB nHL for left and right
      ears. At four testing frequencies of ASSR, the thresholds are (86.91 +/- 16.70),
      (90.32 +/- 16.11), (91.02 +/- 16.58), (89.80 +/- 17.08) and (85.15 +/- 18.16),
      (89.32 +/- 17.76), (90.41 +/- 18.87), (85.15 +/- 17.03) dB HL for left and right
      ears. The correlation coefficients between the ASSR and ABR of left and right
      ears are 0.622, 0.721, 0.757, 0.714 and 0.613, 0.732, 0.795, 0.739 at these
      frequencies respectively. These results showed significant correlation exiting.
      CONCLUSION: Reliable and frequency specific results could be obtained by ASSR so
      that it could be as a promising audiometry in clinic.

PMID- 16463765
TI  - [Study on the correlation of substance P in middle ear effusion and clinical
      presentation in secretory otitis media].
AB  - OBJECTIVE: To investigate the correlation of substance P in middle ear effusion
      and clinical presentation in secretory otitis media. METHOD: Observation on
      relation between clinical presentation (the course of disease, the hearing loss,
      quantity of middle ear effusion or quality) and substance P (SP) content of
      middle ear effusion (MEE) in 64 cases (79 ears) of secretory otitis media (SOM).
      RESULT: SP concentration of MEE in serous group was remarkably higher than that
      in the mucous group (P < 0.01). SP concentration of MEE had positive correlation
      with the volume (r = 0.985, P < 0.01), and negative correlation with the course
      of disease (r = -0.6217, P < 0.01). The hearing loss of mucous group was
      remarkably higher than that of the serous group (P < 0.01). SP concentration of
      MEE in serous group had positive correlation with auditory threshold (r = 0.9553,
      P < 0.01). SP concentration of MEE in mucous had no correlation with auditory
      threshold. CONCLUSION: SP might play an important role in SOM. The detection of
      SP content in MEE is of important significance for judging quality of MEE and
      understanding the course of disease.

PMID- 16463766
TI  - [Clinical study on canalith repositioning procedure for benign paroxysmal
      positional vertigo of semicircular canal].
AB  - OBJECTIVE: To determine the effectiveness of canalith repositioning procedure for
      the treatment of benign paroxysmal positional vertigo (BPPV). METHOD: Medical
      records from two hundred and thirty cases with benign paroxysmal positional
      vertigo treated between January 2002 to June 2004 were analyzed retrospectively.
      Patients were divided into two groups,treatment group (122 cases) and control
      group (108 cases). Treatment group received a single treatment of canalith
      repositioning procedure based on the hypothesis that the vertigo and nystagmus of
      BPPV were due to debris floating in the long arm of the semicircular canal.
      Treatment outcome was analyzed after two weeks classified as cure, improvement or
      no change. RESULT: After a single treatment of canalith repositioning procedure,
      the vertigo and nystagmus in 88 cases of treatment group immediately or gradually
      disappeared in 1-2 weeks, 18 cases improved, 16 cases got no effect. Complete
      remission of vertigo and nystagmus was found in 72.1%, the total improvement rate
      was 86.9%. The vertigo and nystagmus in 51 cases of control group immediately
      disappeared in 1-2 weeks, 23 cases improved, 34 cases got no effect. Complete
      remission of vertigo and nystagmus was found in 47.2%, the total improvement rate
      was 68.5%, and the difference between groups was very significant (P < 0.001, P <
      0.01). CONCLUSION: The canalith repositioning procedure was effective for most
      patients with benign paroxysmal positional vertigo and can be recommended as the
      first-line treatment modality.

PMID- 16463767
TI  - [Value of the different positioning tests in diagnosis of benign paroxysmal
      positional vertigo].
AB  - OBJECTIVE: To ascertain the value of different positioning tests in diagnosis of
      benign paroxysmal positional vertigo (BPPV). METHOD: Seventy-two patients who had
      determined the diagnosis of the posterior semicircular canal BPPV (PC-BPPV) in
      our department from Feb. 2000 to Apr. 2004 was tested with different positioning
      maneuvers. All cases were randomly divided into 2 groups with cross-over design.
      Group A with 36 subjects was tested with the Dix-Hallpike maneuver followed up by
      side-lying maneuver; Group B was tested in reverse order. Then, the Roll test was
      performed. RESULT: The results had association (P > 0.01) between the Dix
      Hallpike maneuver and side-lying maneuver, and the positive rate had no
      significant difference (P < 0.01). The features of vertigo and nystagmus provoked
      by the tests were the same. One patient was found combining with BPPV of
      horizontal semicircular canal (HC-BPPV) by the Roll test. CONCLUSION: As the Dix
      Hallpike maneuver, the side-lying test has the same diagnostic value in determine
      the PC-BPPV. Because it is safer and easier to perform in the condition of range
      of-motion limitations such as spondylosis, it can alter the Dix-Hallpike
      maneuver. If the horizontal nystagmus provoked in above tests, the Roll test
      should be perform also to determine whether combining with HC- BPPV or not.

PMID- 16463768
TI  - [To analyze 125 patients associated with chronic nasal obstruction through
      hypothermia plasma operative system on nasoendoscopy].
AB  - OBJECTIVE: To investigate the change of nasal airway resistance (NAR) before and
      after operation with the treatment of Temperature-controlled radiofrequency
      (TCRF) for chronic nasal obstruction on nasal endoscope. METHOD: In 125 patients
      of chronic nasal obstruction, the inferior turbinate volume was reduced with the
      treatment of TCRF. With anterior rhinomanometry, the NAR before and after
      operation were measured and compared. RESULT: The NAR decreased obviously after
      surgery, which indicated a remarkable significance (P < 0.01) on pre-operation
      and post-operation. CONCLUSION: TCRF operation through nasal endoscope may have
      some advantages of affirmative effect with subtle wound. It is less painful and
      easier to recover, which is worth to be generally applied.

PMID- 16463769
TI  - [Expressions of cystic fibrosis transmembrane conductance regulator in epithelial
      cells of nasal polyps and normal turbinate mucosae].
AB  - OBJECTIVE: To investigate the role of cystic fibrosis transmembrane conductance
      regulator (CFTR) in human nasal polyps. METHOD: CFTR were studied in 28 cases of
      nasal polyps and 7 cases of normal turbinate mucosae with immunochemistry
      staining. RESULT: (1) CFTR was detected in the two tissues and localized mainly
      in epithelial cells and secretory cells. Its staining showed a more prominent
      feature in nasal polyps than in normal turbinate mucosae. CFTR showed a typical
      apical distribution in the normal turbinate mucosae whereas, in the nasal polyps,
      CFTR demonstrated the other pattern of localization comprising cytoplasmic
      distribution and typical apical location. (2) Both the CFTR staining intensity of
      apical and cytoplasmic distribution in the epithelial cell layer from nasal
      polyps were higher than those from turbinates (P < 0.05, P < 0.05 respectively).
      CONCLUSION: Over expression and dysfunction of the chloride channels CFTR may
      play a role in the formation of nasal polyps.

PMID- 16463770
TI  - [Methylprednisolone pharmacokinetics in perilymph and plasma of guinea pig after
      topical administration and intracardial injection].
AB  - OBJECTIVE: To determine pharmacokinetics profiles of methylprednisolone (MTH) in
      perilymph and plasma of guinea pig after topical and systemic administration.
      METHOD: A granule gelfoam soaked with MTH (40 mg/ml) was placed in the niche of
      round window of guinea pig; otocyst was infused with MTH (40 mg/ml); 4 mg/kg of
      MTH was injected intracardially. Samples of blood and perilymph of the scala
      tympani were obtained 1-6 h after administration of two routes, respectively.
      High-performance liquid chromatography was used to assay MTH in the samples.
      RESULT: After intracardial injection of MTH, concentrations of drug in plasma
      were obviously higher than those of in perilymph in every hour while drug in
      perilymph could not be obtained in 4-6 h, and the results were significantly
      different. After niche was placed with granule gelfoam with drug or otocyst was
      infused with MTH,drug could not be obtained in plasma, concentrations of drug in
      perilymph were obviously higher than those of in plasma after intracardial
      injection,and the highest concentrations in perilymph were manifested in 1 h 20
      min. The concentrations of drug in perilymph after otocyst was infused with MTH
      were higher than those of after niche was placed with granule gelfoam soaked with
      MTH in every hour, and there were significant differences in between except those
      in 4 and 6 h. The half-life time of MTH in perilymph after otocyst was infused
      was 1.51 h, and the one after niche was placed with granule gelfoam soaked with
      MTH was 1.55 h. CONCLUSION: MTH could penetrate effectively through membrane of
      round window into the cochlear fluid and reach a much higher concentration
      following topical administration as compared with systemic application. The
      concentrations of drug in perilymph after otocyst was infused with MTH were
      higher.

PMID- 16463771
TI  - [Survey on pollen sensitization of tropic plants in Haikou].
AB  - OBJECTIVE: To discover varieties of sensitization pollens and improve specific
      diagnosis against tropic pollinosis by the field survey of tropic plants. METHOD:
      (1) All of the chosen 20 tropic plants widely located, with enormous quantity and
      more pollens were identified the family, genus and species by specialists. And
      their pollens gathered in full bloom period were delivered to the chemical
      reagent works of union Hospital, Beijing and manufactured, according to clinical
      standards, into idiotoxins. (2) Five hundred patients were chosen randomly from
      May, 2003 to August, 2004 among those who came to our department and were
      suffering from allergic rhinitis, slow urticaria, allergic taraxis, allergic
      asthma and deviancy asthma. They were aged 5-72, altogether 285 male and 215
      female, and agreed to be observed. Experiments included skin pricking and
      intracutaneous test. RESULT: The 20 clinical skin prick tests of tropic plants
      pollens idiotoxin proved that the positive reaction rate was 5 of which was over
      50%, 6 of which 40%-49%, 3 of which 30%-39%, 4 of which 20%-29%, 2 of which 10%
      20%, 40%-49%. CONCLUSION: The tropic plants survey, pollen gathering, idiotoxin
      manufacturing, clinic intracutaneous test and sensitization discovery have not
      only increased varieties of tropic sensitization pollen idiotoxins but also
      improved specific diagnosis of pollinosis in tropic areas.

PMID- 16463772
TI  - [Modified transcranial orbitotomy for treating exophthalmic intraorbital tumor].
AB  - OBJECTIVE: To study the feasibility of the modified osteotomy of transcranial
      orbitotomy in the treatment of intraorbital tumor. METHODS: We treated 8 patients
      with intraorbital tumor during six years. By the bicoronary incision, all cases
      underwent double bone flap osteotomy on the frontal bone: the superior orbital
      rim bone flap and roof flap instead of single fronto-orbital bone flap in the
      conventional transcranial orbitotomy. After removal of bone flaps, intracranial
      and intraorbital operation was performed. Then, two bone flaps were reduced
      respectively and fixated with titanic micro-plates and nails. At last, the scalp
      flap was sutured. RESULTS: The operative field was very well exposed. It was
      found that the retrobulbar tumor was located at the superolateral, median and
      superonasal area respectively, which was coincided with the preoperative CT and
      MRI. The tumor included adenocarcinoma of the lacrimal gland, neurinoma,
      meningioma, and cavernous hemangioma. Four patients had blood transfusion during
      the operation. No other postoperative complications happened except 3 cases of
      diplopia and one case of blindness. After 3 to 6 months follow up, diplopia of
      the 3 cases gradually disappeared. Of the 8 cases, 6 reached the same visual
      acuity as the preoperative state. One decreased visual acuity and one lost light
      perception. There was well-balanced fronto-orbital appearance and eyeball
      position compared with the healthy side in all cases. CONCLUSIONS: This surgical
      method for the treatment of intraorbital tumor is safe with well-exposed
      operative field. It has advantages not only in simpleness and less trauma, but
      also in keeping orbital roof and anterior fossa intact and decreasing
      complications.

PMID- 16463773
TI  - [Clinical study of surgical treatment of ankylosis of temporomandibular joint].
AB  - OBJECTIVE: To analyze the clinical feature of temporomandibular joint (TMJ)
      ankylosis and to investigate the advantage and disadvantage of all kind of
      surgery methods of TMJ ankylosis for supplying references to the treatment of TMJ
      ankylosis. METHODS: Aetiology, sex, age at time of treatment, clinical features,
      radiographic findings, surgical treatment was reviewed and analyzed. RESULTS:
      Trauma (66.86%, n = 117) and infection (24.57%, n = 43) were the primary causes
      of TMJ ankylosis. The 10 approximately 19 years age group (44.57%, n =78)
      occupied the highest frequency in five age groups, one hundred and fourteen
      (65.14%, n = 114) of the patients presented with lateral ankylosis. They were
      carried out different surgery method according to their difference of age,
      aetiology, and so on. CONCLUSIONS: The person at 10 approximately 19 years old
      had the more feasibility of TMJ ankylosis than others. Trauma was the commonest
      cause of ankylosis. Different surgical method should be choose according to the
      different patient.

PMID- 16463774
TI  - [Correction of dento-maxillofacial deformities following cleft lip and palate
      repair with orthognathic surgery and orthodontics].
AB  - OBJECTIVE: To restore good occlusion and face profile, the orthognathic operation
      and orthodontics were used to correct the dento-maxillofacial deformities
      following the repair of cleft lip and palate. METHODS: 21 patients (7 males and
      14 females, mean age of 20.6 years) were included in this study. Their dento
      maxillofacial deformities following the repair of cleft lip and palate have been
      corrected in our hospital since 1996. Of them, 17 patients received pre- and
      postoperative orthodontic treatments. 21 cases underwent the following surgical
      procedures: Le Fort I osteotomy in 7 cases, multisegmental Le Fort I osteotomy in
      5 cases, Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO)
      in 4 cases, Le Fort I osteotomy and mandibular body osteotomy in 2 cases, BSSRO
      and genioplasty in 2 cases, BSSRO in 1 case. Rigid internal fixation was used in
      all patients. After multisegmental Le Fort I osteotomy, the rigid fixed palatine
      splint was used for 6 approximately 8 weeks. RESULTS: Osteotomy segments healed
      well in all cases without severe complications. 14 patients were followed-up for
      an average of 25.6 months. There was no evident relapse. 12 patients who received
      pre- and postoperative orthodontic treatments had satisfactory occlusion and face
      profile. CONCLUSIONS: Orthognathic operation combined with orthodontics can be
      used satisfactorily to correct the dento-maxillofacial deformities following
      cleft lip and palate repair.

PMID- 16463775
TI  - [Scanning electron microscopic study of titanium-hydroxyapatite, the functionally
      graded-material implanted in rabbits].
AB  - OBJECTIVE: The purpose of this study was to observe the tissue tolerance of Ti-HA
      functionally graded-material (FGM) and the form of the material-bone interface.
      METHODS: The sintered Ti -HA FGM, pure HA and pure Ti were respectively implanted
      into the parietal bone of rabbits. The specimens were observed by SEM at 2, 4, 8
      postoperative weeks. RESULTS: In the early stage, the new bone surrounding the Ti
      -HA FGM formed earlier with larger amount and better maturity than the pure Ti.
      The condition was similar to the pure HA. Two months after the operation, direct
      bonding of material-bone interface was formed between the Ti -HA FGM and the new
      bone as an integral body. However, there was a little space left between the new
      bone and the pure Ti. CONCLUSIONS: The Ti -HA FGM has good tissue tolerance. Its
      early integration with bone is similar to pure HA and better than pure Ti.

PMID- 16463776
TI  - [The clinical experience in transplantation of the anterolateral femoral skin
      flap].
AB  - OBJECTIVE: To introduce the clinical experience in transplantation of the
      anterolateral femoral skin flap. METHODS: A total of 625 anterolateral femoral
      skin flaps in 600 patients were transplanted from 1988 to 2003. The retrospective
      analysis was carried out in all the cases as to the flap pedicle, the vascular
      variations, the surgical procedures and modifications, and the adaptation for a
      cutaneous-branch-absent flap. RESULTS: The 625 flaps were transferred except 7
      cancelled in the operation. Postoperatively, 17 cases encountered vascular
      complications, 10 of which survived completely with successful vessel
      exploration, 3 cases had partial necrosis, and 4 cases had complete necrosis. The
      survival rate was 97.8%. 545 flaps were pedicled with the descending branch or
      lateral branches; 45 flaps with the transverse branch or the high-site
      anterolateral cutaneous artery, 10 cases with the descending-transverse branch,
      18 cases with other vessels. 7 cases were found cutaneous-branch-absent. The
      vessel variation rate of the flap was 4.06%. CONCLUSIONS: The anterolateral
      femoral skin flap has less variation of its pedicle and high success rate of
      operation. It is an ideal choice for repair of soft tissue defects in the
      extremities.

PMID- 16463777
TI  - [The expanded cross-leg flap for repairing the soft tissue defects of the
      instep].
AB  - OBJECTIVE: To explore the clinical application of the expanded cross-leg flap for
      repairing instep soft tissue defects with bone exposure. METHODS: The expanded
      cross-leg flap was used to repair instep defects in 10 patients. After flap
      transferring the donor site was closed directly without skin grafting. RESULTS:
      Satisfactory results were achieved in all the cases. The flaps survived well. The
      donor site had less scar and kept good appearance. CONCLUSIONS: The expanded
      cross-leg flap is a better choice for repairing the soft tissue defects of the
      instep. It is simple and easy with less trauma to the donor site. After the
      operation, both the recipient and the donor areas had good appearance.

PMID- 16463778
TI  - [Use of lower trapezius musculocutaneous pedicle flap in repairing of
      maxillofacial region penetrating defect].
AB  - OBJECTIVE: To investigate an safe and effective new technology (treatment) to
      repair maxillofacial region penetrating defect. METHODS: The lower trapezius
      musculocutaneous flap is parallel just like as two leaves which is connected to
      each other, and was folded to provide the liner of oral cavity and external
      cover. RESULTS: Totally twelve folding lower trapezius musculocutaneous pedicle
      flap survived. Postoperative follow-up for 1 approximately 3 years, the patients
      restored the function as well as the shape of maxillofacial region. CONCLUSIONS:
      The lower trapezius musculocutaneous pedicle flap is a suitable material for
      maxillofacial region reconstruction, further more, the successful rate is
      perfect.

PMID- 16463779
TI  - [Inner preputial skin grafts combined with preputial island flap for treatment of
      penile hypospadias].
AB  - OBJECTIVE: To investigate new methods of treatment for penile hypospadias.
      METHODS Urethroplasty was performed for penile hypospadias using inner preputial
      skin grafts combined with preputial island flap. RESULTS: A total of 10 patients
      have received this procedure. After a mean follow up of one year, no fistula or
      urethral stricture was found. All patients obtained excellent cosmetic results.
      CONCLUSIONS: This method allows for adequate correction of severe chordee. It is
      a useful procedure for selected cases of primary hypospadias with severe
      incurvation.

PMID- 16463780
TI  - [Experiment of augmenting the survival areas of ischemic flap by transplanting
      endothelial progenitor cells].
AB  - OBJECTIVE: To investigate the feasibility of transplanted endothelial progenitor
      cells to ischemic flap with increased neovascularization and augmented the
      survival areas. METHODS: EPCs were isolated from human cord blood, cultured in
      vitro, identified by immunohistochemistry. Then EPCs were transplanted to
      ischemic flaps of 9 nude mice's back (experimental group), and 9 nude mice's back
      flaps was injected with M199(control group). And pedicle division time was 4 days
      after operation. CM-DiI was used to trace the transplanted cells. The blood
      perfusion of flaps was monitored by the laser Doppler flowetry, and the capillary
      density of flaps was detected by CD34 immunohistochemistry. RESULTS: EPCs
      expressed cell markers CD34, KDR and CD133. Transplanted EPCs survived and was
      incorporated into the capillary networks in the ischemic flaps of nude mice. The
      percent of experimental group's flap survival area was (60.3 +/- 2.1)%,
      significantly higher than the control group[ (34.2 +/- 1.8)%, P < 0.05 ]. The
      blood perfusion, capillary density of flaps of experimental group was
      significantly higher than the control group (P < 0.05). CONCLUSIONS: EPCs from
      human cord blood can increase ischemic flaps neovascularization and augment the
      survival areas.

PMID- 16463781
TI  - [The relationship between the changes in the blood flow of the exceedingly
      expanded skin and the viability of the flap].
AB  - OBJECTIVE: To investigate the relationship between the blood flow of the
      exceedingly expanded skin and the viability of the flap. METHODS: The piglets
      were set up as the animal model. They were divided into 7 groups according to
      different injection volume of the tissue expander, i. e. injection to 1/2
      content, 3/4 content, full content, 50% over content, 100% over content, sham
      operation control and normal control. At different stages of expansion, the blood
      flow and the amplitude of the expanded skin were examined by laser Doppler. The
      survival length of the expanded flap was measured. Furthermore, statistical
      analysis was performed. RESULTS: As the expansion volume increasing, the blood
      flow and the amplitude of the expanded skin increased, the survival length of the
      expanded flap increased also. In the meantime, the amplitude instability and
      vessel permeability increased. When the injection volume exceeded to 100%, the
      blood flow and the survival length of the expanded flap decreased. CONCLUSIONS:
      In soft tissue and skin expansion, increasing injection volume could increase the
      survival length of the expanded flap, while over-expansion to 100% content may
      cause blood flow disturbance.

PMID- 16463782
TI  - [Preventing scarring in split-thickness skin donor sites with epidermal
      grafting].
AB  - OBJECTIVE: Introducing a new technique for preventing the scar growthing in split
      thickness skin donor sites using the great sheets of epidermis covering. METHODS:
      The donor sites of split thickness skin were grafting with the great sheets of
      the epidermis, of the thickness about 0.07 approximately 0.12 mm, harvested by
      electrical power dermatome and fixed the edges of the epidermal sheet with the
      verges of donor wound together using the nanoparticles-Ag-gauze stripes adding
      the sutures or skin stapler, dressing the wounds with the nanoparticles-Ag-gauze
      using the tie-over technique, left the dressing entire for a 5-day period.
      RESULTS: This method were used in a total of 209 donor sites of both the split
      thickness skin and epidermis for 133 reconstructed sites of 118 cases from
      November 1999 to November 2003, and the smooth, near normal skin appearance
      without scarring were obtained in the split thickness skin donor sites, and the
      epidermal donor sites healed good enough 5 days after surgery, and skin
      appearance is near normal in 3 months later. CONCLUSIONS: Covering the donor
      sites of split thickness skin with the large sheets of epidermis is an effective
      and useful method for preventing the scarring in the split thickness skin donor
      sites.

PMID- 16463783
TI  - [The influence of adrenaline on the expression of TGF-beta1, bFGF and I
      procollagen for hypertrophic scar].
AB  - OBJECTIVE: To investigate the influence of adrenaline on the expression of
      TGFbeta1, bFGF and procollagen for human normal and hypertrophic scar dermal
      fibroblasts cultured in vitro. METHODS: Human normal and hypertrophic scar dermal
      fibroblasts were propagated in a serum-free in vitro model with adrenaline for 24
      hours. The human mRNA levels of bFGF, TGF-beta1 and I procollagen in fibroblasts
      were determined by RT-PCR. Levels of bFGF and TGF-beta1 in the supernatants of
      fibroblasts cultured in vitro were determined by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: In our study, adrenaline caused statistically significant
      increase in the peak levels of bFGF for normal and hypertrophic scar fibroblast
      cell lines (P < 0.01). It also caused statistically significant decrease in the
      level of TGF-beta1 for normal and hypertrophic scar fibroblast cell lines.
      Modulation of normal fibroblasts with 0.05, 0.10 and 0.20 micromol/L adrenaline
      resulted in a statistically significant (P < 0.01) decrease in the expression of
      I procollagen mRNA. However, only 0.20 micromol/L adrenaline can decreased the
      mRNA expression of I procollagen in the hypertrophic scar fibroblasts.
      CONCLUSIONS: We conclude from these results that adrenaline can increase the
      production of bFGF and decrease production of TGF-beta1 and I procollagen in
      human normal dermal and hypertrophic scar fibroblasts cultured in vitro.

PMID- 16463784
TI  - [Expression and significance of TRAIL receptors in fibroblasts of hypertrophic
      scar].
AB  - OBJECTIVE: To detect the expression of TRAIL receptors in fibroblasts of
      hypertrophic scar in the proliferative stage and explore its significance.
      METHODS: 30 samples of hypertrophic scar were taken from 30 burn cases in the
      proliferative stage. 30 samples of normal skin were taken as the control. The
      expressions of TRAIL receptors in the fibroblasts of hypertrophic burn scar and
      the normal skin were assayed by semiquantitative RT-PCR and flowcytometry.
      RESULTS: The expression level of DR5 in the fibroblasts of hypertrophic burn scar
      is much lower than the control (P < 0.05); the expression level of DcR1 in the
      fibroblasts of hypertrophic burn scar is much higher than the control (P < 0.05).
      CONCLUSIONS: The down-regulated DR5 expression and elevated DcR1 expressions in
      the fibroblasts of hypertrophic burn scar may attribute to the apoptosis change
      induced by TRAIL and explain the apoptosis differences between the fibroblasts of
      hypertrophic scar and normal skin to a certain extent.

PMID- 16463785
TI  - [Expression and significance of Skp2 and p27kip1 protein in pathological scar].
AB  - OBJECTIVE: To study the expression of Skp2 gene (s-phase kinase associated
      protein 2) in the pathological scars and its relationship with p27kip1 level and
      to investigate its role and its probable mechanism in the pathogenesis of
      abnormal scars. METHODS: Immunohistochemical technique was performed to detect
      the expression and distribution of Skp2 and p27kip1 protein in hypertrophic scar
      (42 cases), keloid (18 cases), normal scar (40 cases) and normal skin (50 cases),
      statistics was used to analyze the data. RESULTS: The positive rate of Skp2 and
      p27kip1 protein expression was not statistically different between the
      hypertrophic scar and keloid (P > 0.05), while they were all remarkably
      significant in comparison between normal scar and abnormal scar (P < 0.05). In
      pathological scar the protein of Skp2 and p27kip1 showed a strong inverse
      correlation (P < 0.01). CONCLUSION: The result indicated that the expression of
      Skp2 was increased and it may lead to decrease p27kip1 level in the hypertrophic
      scar and keloid, Skp2 overexpression might play an important role in the
      proliferation of fibroblasts and in the pathogenesis of pathological scar by
      adjusting the regulation of cyclins such as p27kip1.

PMID- 16463786
TI  - [Following the fate of murine epidermal stem cells in a syngeneic dermal
      equivalent in vivo].
AB  - OBJECTIVE: To follow the fate of murine epidermal stem cells (ESCs) seeded in a
      syngeneic dermal equivalent implanted in vivo. METHODS: Embryonic stem (ES) cells
      were induced in vitro to differentiate into ESCs. After stained with a
      fluorescent dye Hoechst 33342, these ESCs were seeded into a fibroblast-collagen
      gelatin sponge complex, functioning as a dermal equivalent model, and implanted
      subcutaneously into 129/J mice, which were syngeneic to these stem cells. The
      fate of these cells was observed with HE staining, immunocytochemical staining or
      Van Gieson's staining. RESULTS: These ESCs were clearly visible in the implant by
      fluorescent microscopy 3 weeks or longer after implantation. These cells remained
      viable, differentiated into hair follicle-like structure, glandular structure,
      and gave rise to additional structures displaying features resembling native
      dermis. A number of markers were expressed in the differentiated structures,
      including CD29 (integrin beta1 subunit) and cytokeratin 18 (CK18). No apparent
      rejection or severe side effects were observed at least during the 10 weeks
      following implantation. CONCLUSION: Now that ESCs could survive in vivo in this
      dermal equivalent model, and differentiate into hair follicle-like structures as
      well as glandular structures, it is feasible to use these cells as seed cells in
      the study to fabricate dermal equivalent having the potential to develop dermal
      appendages.

PMID- 16463787
TI  - [Microsurgical reconstruction of the nasal subunit defects].
AB  - OBJECTIVE: The nose is composed of several delicate subunits, some of which are
      difficult to reconstruct if they have been injured. The paper presents the
      microsurgical technique to repair the nasal subunit defects with the free
      combined preauricular and auricular flap which well match the nasal tissues in
      texture, contour and color. METHODS: The nasal subunit defects were repaired with
      the combined preauricular and auricular flap which were vascularized by the
      superficial temporal vascular system. The flap was harvested from the
      contralateral preauricular and the region of helix crus. The superficial temporal
      vessels were anastomosed to facial vessels via the vascular grafts harvested from
      the lateral circumfluent femoral vessels, which were about 10 to 14 cm in length.
      The helix crus of donor ear was reconstructed with the post-auricular flap.
      RESULTS: 28 cases were treated, including 3 cases of nasal tip defects, 9 cases
      of combined nasal alar and sidewall defects, and 16 cases of nasal alar defects.
      In these cases, the size of the subunit defects varied from 2.5 cm x 1.5 cm to 4
      cm x 2.5 cm. 27 cases were successfully repaired with satisfactory results. The
      contour of reconstructed helix crus in donor site was acceptable. No walking
      dysfunction of the donor thigh was complained. There is one failed case, and the
      possible reason is the insufficient blood perfusion to the flaps, which may due
      to the patient's longtime-smoking status and the hypertension. CONCLUSIONS: The
      technique of free combined preauricular and auricular flap is ideal for the
      reconstruction of nasal subunit defects.

PMID- 16463789
TI  - [Analysis of complications induced by polyacrylamide hydrogel injection for
      augmentation mammaplasty].
AB  - OBJECTIVE: To analyze the complications induced by polyacrylamide hydrogel
      injection for augmentation mammaplasty, explore the reason of the complication.
      METHODS: Twenty three patients with complications after polyacrylamide hydrogel
      injection were classified by signs and symptoms, ultrasound and pathologic
      examinations were made. RESULTS: The main complications were pain, hard nodule,
      asymmetry and breast deformation. The injected material was distributed diffusely
      behind gland, in gland, in muscles subcutaneous, even out of breast, caused some
      pathologic changes and it's hard to be cleaned completely from normal tissue.
      CONCLUSIONS: The complications were caused mainly by incorrect manipulation
      during operation, others might be relative to the injected material. The
      reliability of this injection method for augmentation should be cautiously
      observed.

PMID- 16463788
TI  - [Plastic surgical treatment of extensive hemangiomas in the oral and
      maxillofacial regions in children].
AB  - OBJECTIVE: To evaluate plastic surgical procedures for the extensive soft tissue
      hemangiomas in the oral and maxillofacial regions in children and to explore
      prevention methods from surgical complications. METHODS: 134 patients with
      hemangiomas were surgically treated. The defects of soft tissue were repaired
      with pedicle flaps or skin grafts. Of the 134 patients, 16 were newborns, 91
      infant, 16 at preschool age and 11 at school age. The location of hemangiomas
      included parotid gland (39.6%), lip (20.9%), buccal (20.1%), suborbital (9%),
      orbital (7.5%) and nasal region (3%). RESULTS: Follow-up from 6 months to 5 years
      showed that the cure rate was 80.6%, apparently effective rate was 15.7%,
      effective rate was 2.2% and ineffective rate was 1.5%. No major surgical
      complications were found. CONCLUSION: Extensive hemangiomas in the oral and
      maxillofacial regions in children were treated safely using plastic surgical
      procedures with satisfactory results esthetically and functionally.

PMID- 16463790
TI  - [Factors influencing today's Swiss medical interns. An interview].

PMID- 16463792
TI  - [Understanding Raynaud's phenomenon: towards a better treatment].
AB  - The Raynaud's phenomenon seems to be well known among the health care workers. It
      has been identified a long time ago, as Maurice Raynaud described the phenomenon
      which bears his name in 1862. However its true definition is often forgotten.
      Moreover the Raynaud's phenomenon is easily confounded with other entities like
      acrocyanosis... The topic of this review has firstly been chosen in order to
      precise the criteria of the Raynaud's phenomenon, secondly to mention the new
      pathogenic aspects recently described and the new therapeutic interventions
      developed in this field.

PMID- 16463791
TI  - [Allergo-immunology].
AB  - Allergic rhinitis is a frequent illness. New therapeutic options are being
      developed to counteract its impact on quality of life and health costs. This
      article presents two of these options, laser rhinophototherapy and Butterbur Ze
      339, a drug derived from petasites. The immunodepressing effect of phototherapy
      has been tested in nasal mucosa. This application has shown satisfactory anti
      inflammatory results in nasal cleaning fluid and, consequently, has enabled to
      reduce allergic rhinitis. The effect of butterbur on the symptoms of allergic
      rhinitis has to be understood in relation with the inhibition of cysleucotrienes
      synthesis, as well as its action on eosinophils and mastocytes. However, long
      term studies involving large cohorts of patients are needed if we want to
      prescribe these treatments without restrictions.

PMID- 16463793
TI  - [Visceral surgery].
AB  - Visceral surgery has benefited from several significant therapeutical
      improvements in 2005. They involve more specifically endocrine surgery, obesity,
      ovarian cancer, rectocele and cystic pancreatic neoplasia. Minimal invasive
      surgery is increasingly used, for example in endocrine conditions and obesity
      treatment. New techniques also emerge, such as electrical gastric stimulation for
      obesity or Stapled Trans Anal Rectal Resection (STARR) for anterior rectocele.
      Accurate diagnosis criteria allow better management of cystic pancreatic
      neoplasia, especially to choose the best treatment of this condition.

PMID- 16463794
TI  - [Dermatology].
AB  - We are going over therapeutic acquisitions in a club-journal including relevant
      publications in different fields: mecanism of action, therapeutic perspectives in
      a near future, and side effects.

PMID- 16463795
TI  - [Are pioglitazone and fenofibrate effective for the prevention of cardiovascular
      disease in type 2 diabetes?].
AB  - This year, two prospective randomized studies aimed at the reduction of composite
      cardiovascular endpoints in type 2 diabetic patients. The PROactive study
      estimated the impact of pioglitazone in the secondary prevention. The significant
      reduction of the primary composite endpoint was not obtained: reduction of the
      relative risk (RR) of 10 % (p= 0.095). However, the secondary composite endpoint
      was significantly reduced RR 16 % (p = 0.027). The FIELD study also had the same
      objectives. The primary composite endpoint was not significantly reduced in spite
      of a RR of 11% while the reduction of RR was significant for the secondary
      composite endpoint (p = 0.035). These studies reveal the difficulties and the
      complexity of the secondary prevention of atherosclerosis for patients already
      treated with effective molecules.

PMID- 16463796
TI  - [Management of gestational diabetes: what's new in 2005?].
AB  - Gestational diabetes is a complication of pregnancy associated with an increase
      in maternal and perinatal morbidity, as well as an increased risk of subsequent
      type II diabetes. Diagnosis can be made by the O'Sullivan test, followed by an
      oral glucose tolerance test. Management of women with gestational diabetes
      involves multidisciplinary collaboration. The treatment includes diet and, if
      necessary, insulin therapy. Until recently, there was no evidence that this
      approach is beneficial. This year, the results of a randomised trial showed a
      reduction of perinatal mortality and morbidity associated with management of
      gestational diabetes.

PMID- 16463797
TI  - [Antihypertensive therapy: who should be treated and to which target?].
AB  - There is no doubt today that hypertensive therapy is effective in preventing
      cardiovascular complications. Having blood pressures 140/190 mmHg repeatedly at
      the doctor's office is associated with an increased cardiovascular risk and
      requires drug treatment if non-pharmacological measures do not allow blood
      pressure normalization. Antihypertensive therapy might already be required in
      patients exhibiting simultaneously blood pressure > or = 130/180 mmHg and
      diabetes and/or renal disease.

PMID- 16463798
TI  - [Medical oncology].
AB  - Patients are more and more often coming to see the physician with reprints from
      the Oracle of modem times, (the Internet). Facing the rapid development of new
      anticancer drugs, even the expert can have difficulties in knowing which ones
      have already rigorous comparative trials and which results are really clinically
      significant, leading to important improvements in the treatment of patients with
      solid tumors. In past years we had already noticed that in some cancer types,
      these progresses unfortunately sometimes remain of marginal importance. Survival
      benefits are not always well established and, confronted with the exploding costs
      of medicine, the physician may not always want to use some promising drugs. This
      review summarizes results of some of the most important randomized clinical
      trials, but does not attempt to solve the cost-benefit question.

PMID- 16463799
TI  - [New trends in corneal surgery. Grafting stem cells and performing lameliar
      graft].
AB  - Epithelial, stromal or endothelial diseases can generate corneal opacity. A lake
      of corneal epithelial cells leads to corneal opacity and low visual acuity. In
      these cases, corneal epithelial stem cells from the limbus of the healthy eye or
      from relatives or other people must be grafted to regenerate corneal epithelium.
      It is also possible to cultivate corneal stem cells harvested from the sick eye,
      the healthy eye (autologous culture) or from relatives (allotypic culture).
      Renewing epithelial cells is not always sufficient to restore corneal
      transparency. It can also be necessary to replace a part or the entire corneal
      stroma. We can use today surgical lamellar graft technics to replace only stromal
      corneal layers involved in the disease we cure.

PMID- 16463800
TI  - [Current progress in pediatrics: obesity and diagnosis approach to the febrile
      child].
AB  - The literature shows that obesity is a public health problem concerning
      especially the general paediatrician. While prevention has probably more chances
      of success than treatment, drugs or, in case of failure, the surgical approach
      are reserved for extreme cases. In the domain of infectiology the different
      laboratory tests allow only partially to diagnose severe infections. But in the
      context of a potential influenza pandemic rapid virologic tests become more and
      more important. They allow a more precise diagnosis and a reduction of
      hospitalisations and of antibiotic prescriptions. A review of the north American
      experience with the pneumococal vaccine shows that the heptavalent vaccine will
      change our approach in infants with fever in whom we suspect a severe infection.

PMID- 16463801
TI  - [Trends in drug therapy].
AB  - This article reviews some recent aspects of pharmacovigilance, of interest to the
      practitioner: biphosphonates and osteonecrosis of the jaw, antidepressants and
      suicide, antipsychotics and increased mortality risk and cerebrovascular events,
      withdrawal syndrome after in utero exposure to antidepressants SSRI, NSAIDs and
      increased cardiovascular events, cancer and topical immunosuppressants, visual
      loss and treatment of erectile dysfunction, valvulopathy and dopaminergic
      agonists. Risk-benefit assessment of drugs is a dynamic process. One must keep in
      mind that the data on the relationship between drugs and the clinical picture are
      of variable quality and that the size of the risk is often difficult to assess.

PMID- 16463802
TI  - [Gout].
AB  - Gout must be regarded as a systemic and chronic disease with potentially serious
      sequelae. Hyperuricemia is probably an independent risk factor for cardiovascular
      diseases, at least in high-risk individuals. Nevertheless, current data do not
      justify for the moment the treatment of asymptomatic hyperuricemia. Finally, if
      allopurinol remains the only available agent in Switzerland for the treatment of
      chronic gout, new molecules, like febuxostat and pegylated uricase, are currently
      being evaluated.

PMID- 16463803
TI  - [Prostate cancer prevention].
AB  - The prevention of prostate cancer is conceivable. Finasteride, even though it
      diminishes the risk of cancer in the male adult, cannot be used as a prophylaxis
      in chemoprevention so far as we do not know if they produce more aggressive
      cancers. On the other hand, weight control, through a varied and balanced diet,
      rich in lycopene, soja beans, omega 3 acid, selenium, vit E, physical and sexual
      activity and no smoking are without risks, efficient and commendable.

PMID- 16463805
TI  - [Discovery of an immune response controlling the spread of colorectal cancer
      metastasis].

PMID- 16463806
TI  - [When the Avian virus (H5N1) become resistant to Tamiflu and the resulting
      consequences].

PMID- 16463807
TI  - [The truth about professor Hwang Woo-Suk (2)].

PMID- 16463808
TI  - [Professor Hwang Woo-Suk is a liar].

PMID- 16463809
TI  - The importance of translational research in brain injury.
AB  - Progress in the understanding of the pathophysiologic process and management of
      brain injury provides a unique challenge to the young investigator. Currently,
      there are teams both in the laboratory and clinical settings which may or may not
      interact as a result of the depth and breadth of the problems before them. For
      example, laboratory teams may be focused on cellular or molecular mechanisms of
      injury while the clinical investigator is attempting to deal with refractory ICP
      and it's treatment. It is clear that many aspects of biological research must
      indeed be approached using molecular techniques of neuroscience and much has been
      learned. However, the translational aspect of this effort may be elusive as it is
      unclear at present how these molecular techniques translate into the intensive
      care unit and the patient. For many, the research paths taken in the laboratory
      and ICU will always remain independent. For those who desire a more direct
      pathway to treatment, the "bench to bedside" approach is one which is more likely
      to yield results. Several examples will be given to strengthen the notion that we
      must not abandon the translational aspect of research but to embrace the process
      if we are to further improve outcome from brain injury.

PMID- 16463810
TI  - Cerebral blood flow (CBF)-directed management of ventilated head-injured
      patients.
AB  - OBJECTIVE: Ischaemic brain damage has been shown to be an important contributing
      factor causing head injury fatality. Maintenance of an adequate cerebral
      perfusion pressure is difficult in patients with elevated intracranial pressure
      (ICP) and deranged cerebral vasoreactivity. Thirty-five cases of ventilated
      moderate-to-severe head-injured patients were prospectively studied, correlating
      their cerebral haemodynamic abnormalities, neurochemical disturbances (using
      microdialysis methodology) and clinical outcome. METHODS: Cerebral haemodynamic
      abnormalities were defined and classified by transcranial Doppler ultrasonography
      (TCD) and stable xenon-CT cerebral blood flow measurements (XeCT) into their
      status of CO2 reactivity, pressure autoregulation, hyperaemia or non-hyperaemia.
      Two-hour episodes of these abnormalities with and without haemodynamic
      intervention were followed in their changes in ICP, CPP, intracerebral
      metabolites and finally their clinical outcome. RESULTS: Loss of CO2 reactivity
      was associated with a significantly higher ICP, increasing intracerebral
      metabolites (lactate, glutamate and glycerol) and invariably a fatal outcome.
      Impaired pressure autoregulation was also associated with an elevated ICP, but no
      significant difference in intracerebral metabolites and incidence of favourable
      clinical outcome. Patients with intact CO2 reactivity and impaired pressure
      autoregulation were treated with an elevated CPP in 32 episodes, resulting in a
      significant reduction in ICP, intracerebral glutamate and glycerol and non
      survival. In patients with intact CO2 reactivity and impaired pressure
      autoregulation, eleven episodes of hyperaemia were identified by XeCT. A modest
      20%, blood pressure reduction resulted in a trend towards a reduction of ICP,
      intracerebral glutamate and glycerol and non-survival. CONCLUSIONS: The need for
      haemodynamic intervention in this group of ventilated patients with moderate-to
      severe head inury can be made logical when these abnormalities are identified
      daily. The success of management was reflected by a stable or improved ICP, CPP,
      intracerebral metabolic deranagement and survival.

PMID- 16463811
TI  - Relationship of cerebral perfusion pressure levels to outcome in traumatic brain
      injury.
AB  - This study examined the relationship of cumulative percent time that cerebral
      perfusion pressure (CPP) fell below set thresholds to outcome in individuals with
      traumatic brain injury (TBI). The sample included 157 patients (16 to 89 years of
      age, 79%, male) admitted to an intensive care unit at an academic medical center
      who underwent invasive arterial blood pressure and intracranial pressure
      monitoring. CPP levels were recorded continuously during the first 96 hours of
      monitoring. Initial neurologic status was assessed using the post-resuscitation
      Glasgow Coma Scale. Outcome was evaluated at hospital discharge and at six months
      post-injury using the Extended Glasgow Outcome Scale (GOSE). The relationship of
      cumulative periods of low CPP to outcome was evaluated using hierarchical and
      binary logistic regression analysis, controlling for age, gender, and injury
      severity. Patients experiencing less cumulative percent time below specific CPP
      thresholds were more likely to have better outcome at discharge (55 mm Hg, p =
      .004; 60 mm Hg, p = .008; 65 mm Hg, p = .024; 70 mm Hg, p = .016). Although
      differences in GOSE scores at six months were not significant, those with less
      time below CPP thresholds were more likely to survive. Accumulated episodes of
      low CPP had a stronger negative relationship with outcome in patients with more
      severe primary brain injury.

PMID- 16463812
TI  - Effects of moderate hyperventilation on cerebrovascular pressure-reactivity after
      head injury.
AB  - In volunteers, hyperventilation improves autoregulation. However, in head-injured
      patients, hyperventilation-induced deterioration and improvement of
      autoregulation have been reported. We have re-examined this question using an
      index of pressure reactivity. Thirty patients with severe or moderate head-injury
      were studied. Arterial blood pressure, cerebral perfusion pressure (CPP), and
      intracranial pressure (ICP) were recorded over 20 minute epochs separated by ten
      minutes of equilibration at baseline and during moderate (>3.5 kPa)
      hyperventilation. End-tidal CO2 was constant during each phase of data
      acquisition. Pressure reactivity was assessed using an index 'PRx' based on the
      response of ICP to spontaneous blood pressure changes. Hyperventilation decreased
      PaCO2 from 5.1 +/- 0.4 to 4.4 +/- 0.4 kPa (p < 0.0001). ICP decreased by 3.7 +/-
      2.2 mmHg (p < 0.001). CPP increased by 5.9 +/- 8.2 mmHg (p < 0.001). Overall, PRx
      did not change significantly with hyperventilation. However, there was a
      significant negative correlation between baseline PRx and the change in PRx (r = 
      0.71, p < 0.0001). This suggests that patients with disturbed pressure-reactivity
      may improve, whereas patients with intact pressure reactivity remain largely
      unchanged. Our data suggest that the response of pressure reactivity to
      hyperventilation is heterogeneous. This could be due to hyperventilation-induced
      changes in cerebral metabolism, or the change in CPP.

PMID- 16463813
TI  - Which paediatric head injured patients might benefit from decompression?
      Thresholds of ICP and CPP in the first six hours.
AB  - Severe head injury in childhood continues to be associated with considerable
      mortality and morbidity. Early surgical decompression may be beneficial and the
      objective of this study was to examine the relationship between age-related
      thresholds of mean intracranial pressure (ICP) and cerebral perfusion pressure
      (CPP) over the first 6 hours and age outcome in paediatric head injury patients.
      A total of 209 head injured children admitted to five UK hospitals were studied.
      Patients aged 2 to 16 years were included if they had a minimum of six hours of
      invasive pressure monitoring. Mean values of ICP and CPP over this period were
      calculated and compared to those with independent (good recovery and moderate
      disability) and poor outcome (severe disability, and death) for different age
      groups. There were 148 children with independent outcome (92 good recovery, 56
      moderately disabled), and 61 with poor outcome (30 severely disabled, 31 deaths).
      There was a significant difference between those with independent compared to
      poor outcome in relation to ICP (p < 0.001) and CPP (p < 0.001). Patients were
      divided into three groups according to age. The sensitivity of ICP and CPP in
      predicting outcome was similar for all groups but the specificity differed
      between groups. At a CPP of 50 mmHg the specificity varied between the age groups
      (2 to 6 years: 0.47, 7 to 10 years: 0.28 and 11 to 16 years: 0.10) and similarly
      for an ICP of 25 mmHg (2 to 6 years: 0.53, 7 to 10 years: 0.44 and 11 to 16
      years: 0.38). Younger children may be able to tolerate lower perfusion pressures
      and still have an independent outcome. Our threshold values for young children
      are likely to be important in the identification of patients who might benefit
      from new treatments such as surgical decompression.

PMID- 16463814
TI  - Association between outcome, cerebral pressure reactivity and slow ICP waves
      following head injury.
AB  - OBJECTIVE: To investigate the relationships between slow vasogenic waves ('B
      waves') of intracranial pressure (ICP), pressure-reactivity and outcome after
      traumatic brain injury. MATERIAL AND METHOD: 193 head-injured patients (age 34 +/
      16.7 years; median GCS 6) were monitored from 1997 to 2002. ICP, arterial blood
      pressure (ABP) were continuously monitored. Pressure-reactivity index (PRx) and
      magnitude of ICP slow waves were evaluated using the bed-side computers. RESULTS:
      Distribution of PRx in different outcome groups indicated that pressure
      reactivity was significantly worse in patients with fatal outcome. A magnitude of
      spontaneous slow waves of ICP was gradually decreasing in poorer outcome grades.
      Mortality indicated threshold rise from 20% to 70% when averaged PRx increased
      above 0.3 (p < 0.01). There was no threshold for mortality observed along
      distribution of magnitude of ICP slow waves. Mortality gradually increased when
      the magnitude of slow waves decreased (R = -0.26; p < 0.0001). CONCLUSION:
      Inadequate pressure-reactivity and low magnitude of slow vasogenic waves of ICP
      are associated with fatal outcome after head injury. Based on brain monitoring
      data, differentiation between favourable outcome and severe disability is more
      problematic than differentiation between survivors and non-survivors.

PMID- 16463815
TI  - Quantification of secondary CPP insult severity in paediatric head injured
      patients using a pressure-time index.
AB  - This paper describes and validates a new Cumulative Pressure-Time Index (CPT)
      which takes into account both duration and degree of cerebral perfusion pressure
      (CPP) derangement and determines critical thresholds for CPP, in a paediatric
      head injury dataset. Sixty-six head-injured children, with invasive minute-to
      minute intracranial pressure (ICP) and blood pressure monitoring, had their pre
      set CPP derangement episodes (outside the normal range) identified in three
      childhood age-bands (2-6, 7-10, and 11-16 years) and global outcome assessed at
      six months post injury. The new cumulative pressure-time index more accurately
      predicted outcome than previously used summary measures and by varying the
      threshold CPP values, it was found that these physiological threshold values (<
      or = 48, < or = 52 and < or = 56 mmHg for 2-6, 7-10, and 11-16 years
      respectively) best predicted brain insult in terms of subsequent mortality and
      morbidity.

PMID- 16463816
TI  - The BrainIT Group: concept and current status 2004.
AB  - INTRODUCTION: An open collaborative international network has been established
      which aims to improve inter-centre standards for collection of high-resolution,
      neurointensive care data on patients with traumatic brain injury. The group is
      also working towards the creation of an open access, detailed and validated
      database that will be useful for hypothesis generation. In Part A, we describe
      the underlying concept of the group and it's aims and in Part B we describe the
      current status of the groups development. METHODS: Four group meetings funded by
      the EEC have enabled definition of a "Core Dataset" to be collected from all
      centres regardless of specific project aim. A form based feasibility study was
      conducted and a prospective data collection exercise of core data using PC and
      hand held computer based methods is in progress. FINDINGS: A core-dataset was
      defined and can be downloaded from the BrainIT web-site (go to "Core dataset"
      link at: www.brainit.org). A form based feasibility study was conducted showing
      the overall feasibility for collection of the core data elements was high.
      Software tools for collection of the core dataset have been developed. Currently,
      130 patient's data from 16 European centres have been recruited to the joint
      database as part of an EEC funded proof of concept study. INTERPRETATION: The
      BrainIT network provides a more standardised and higher resolution data
      collection mechanism for research groups, organisations and the device industry
      to conduct multicentre trials of new health care technology in patients with
      traumatic brain injury.

PMID- 16463818
TI  - ICM+: software for on-line analysis of bedside monitoring data after severe head
      trauma.
AB  - ICM software was developed in 1986 in Warsaw, Poland and has been in use at the
      University of Cambridge Neurocritical Care Unit for 10 years collecting data from
      bed-side monitors in nearly 600 severely head injured patients and calculating
      secondary indices describing cerebral autoregulation and pressure-volume
      compensation. The new software ICM+ includes a much extended calculation engine
      that allows easy configuration and on-line trending of complex parameters. The
      program records raw signals, and calculates time trends of summary parameters.
      Configuration and analysis utilises arithmetic expressions of signal processing
      functions to calculate various statistical properties for each signal, frequency
      spectrums and derivatives, as well as correlations/cross-correlations between
      signals. The software allows configuration of several levels of analysis before
      calculating the final time trends. The final data are displayed in a variety of
      ways including simple time trends, as well as time window based histograms, cross
      histograms, correlations etc. All this allows complex information coming off the
      bed-side monitors to be summarized in a concise fashion and presented to medical
      and nursing staff in a simple way that alerts them to the development of various
      pathological processes. The system provides a universal tool for clinical and
      academic purposes. Its flexibility and advanced signal processing is specialized
      for the needs of multidisciplinary brain monitoring.

PMID- 16463817
TI  - Accurate data collection for head injury monitoring studies: a data validation
      methodology.
AB  - BACKGROUND: BrainIT is a multi centre, European project, to collect high quality
      continuous data from severely head injured patients using a previously defined
      [6] core data set. This includes minute-by-minute physiological data and
      simultaneous treatment and management information. It is crucial that the data is
      correctly collected and validated. METHODS: Minute-by-minute physiological
      monitoring data is collected from the bedside monitors. Demographic and clinical
      information, intensive care management and secondary insult management data, are
      collected using a handheld computer. Data is transferred from the handheld device
      to a local computer where it is reviewed and anonymised before being sent
      electronically, with the physiological data, to the central database in Glasgow.
      Automated computer tools highlight missing or ambiguous data. A request is then
      sent to the contributing centre where the data is amended and returned to
      Glasgow. Of the required data elements 20% are randomly selected for validation
      against original documentation along with the actual number of specific episodic
      events during a known period. This will determine accuracy and the percentage of
      missing data for each record. CONCLUSION: Advances in patient care require an
      improved evidence base. For accurate, consistent and repeatable data collection,
      robust mechanisms are required which should enhance the reliability of clinical
      trials, assessment of management protocols and equipment evaluations.

PMID- 16463819
TI  - Survey of traumatic brain injury management in European Brain-IT centres year
      2001.
AB  - BACKGROUND: The aim of this study was to obtain basic knowledge about the current
      local conditions and neurointensive care of traumatic brain injury (TBI) in the
      new multi-centre collaborative BrainIT group. MATERIALS AND METHODS: The survey
      comprised a background part on local policies (Part A), and a case study section
      (Part B). The information was gathered by questionnaire followed by telephone
      interviews. Twenty-three BrainIT centres participated in the survey and answers
      from two respondents were available from 18 of the sites. RESULTS: The average
      proportion of agreement between duplicate respondents was 0.778 (range 0.415
      1.00). All BrainIT centres monitored ICP. The treatment protocols seem to have a
      pattern concerning escalation of treatment of intracranial hypertension: 1/
      evacuation of mass lesions and head elevation; 2/ increased sedation and
      mannitol; 3/ hyperventilation; 4/ ventricular drainage; 5/ craniectomy and
      barbituates. CONCLUSIONS: There seemed to be an agreement on neurointensive care
      policies within the BrainIT group. The suggested order of treatment was generally
      in accordance with published guidelines although the suggested order and
      combinations of different treatments varied. Variation of treatment within the
      range of prescribed standards provides optimal conditions for an interesting
      future analysis of treatment and monitoring data in reality using the BrainIT
      database.

PMID- 16463820
TI  - The importance of major extracranial injuries by the decompressive craniectomy in
      severe head injuries.
AB  - Neurosurgical therapy aims to minimise the secondary brain damage after a severe
      head injury. This includes the evacuation of an intracranial space occupying
      bleeding, the reduction of intracranial volumes, in hematocephalus an external
      ventricular drainage, and the conservative therapy in order to influence an
      increased intracranial pressure (ICP) and a decreased p(ti)02. When conservative
      treatment fails to act a decompressive craniectomy might be successful in
      lowering ICP. From September 1997 until July 2004 we operated on 737 patients
      with severe head injuries. 103 patients (14%) were treated by means of a
      decompressive craniectomy. The prognosis after decompression depends on the
      clinical signs and symptoms on admission, the patients age and the existence of
      major extracranial injuries. Our guidelines for an indication for decompressive
      craniectomy after failure of conservative interventions and evacuation of space
      occupying hematomas include a patients age below 50 years without multiple
      trauma, a patients age below 30 years in the presence of major extracranial
      injuries, a severe brain swelling on CT scan, the exclusion of a primary
      brainstem lesion or injury and the intervention before irreversible brainstem
      damage and secondarily while monitoring ICP and p(ti)02 in an interval up to 48
      hours after the accident before irreversible brainstem damage or generalised
      brain damage has occurred.

PMID- 16463821
TI  - Beneficial effect of cerebrolysin on moderate and severe head injury patients:
      result of a cohort study.
AB  - Cerebrolysin is used as a neurotrophic agent for the treatment of ischemic stroke
      and Alzheimer's Disease. Exploratory studies in patients with post-acute
      traumatic brain injury have shown that this treatment might help improve
      recovery. Aim of this study was to investigate whether addition of Cerebrolysin
      to the initial treatment regimen of moderate and severe head injury patients
      would improve their outcome. At 6 months, 67% of the patients (Cerebrolysin
      group) attained good outcome (GOS 3-5). The study group was compared with the
      historical cohort of patients from the hospital trauma data bank, with age, sex
      and admitting GCS matching. More patients tended to a good outcome in the
      Cerebrolysin group (P = 0.065). No significant side-effect requiring cessation of
      Cerebrolysin was noted. It can be concluded that the use of Cerebrolysin as part
      of the initial management of moderate and severe head injury is safe and well
      tolerated. The results suggest that Cerebrolysin is beneficial in regard to the
      outcome in these patients, especially in elderly patients.

PMID- 16463822
TI  - Re-defining the ischemic threshold for jugular venous oxygen saturation--a
      microdialysis study in patients with severe head injury.
AB  - Neurological change is more likely to occur when jugular venous oxygen saturation
      (SjvO2) is less than 50%. However, the value indicating cellular damage has not
      been clearly defined. We determined the critical SjvO2 value below which
      intracerebral extracellular metabolic abnormalities occurred in 25 patients with
      severe head injury. All patients received standard treatment with
      normoventilation and maintenance of intracranial pressure < 20 mmHg. SjvO2 was
      measured from the dominant jugular bulb using a calibrated fibreoptic catheter.
      Intracerebral metabolic monitoring was performed by collecting perfusate from a
      microdialysis probe placed in the frontal lobe anterior to the intracranial
      catheter. Excitotoxin (glutamate) and other extracellular metabolites (lactate,
      glucose and glycerol) were measured frequently using enzymatic and colorimetric
      methods. We observed biphasic relationships between SjvO2 and all intracerebral
      metabolites. Analysis of variance showed that there were rapid increases in
      glutamate, glycerol and lactate when SjvO2 dropped below 40, 43 and 45%
      respectively. Extracellular glucose decreased when SjvO2 dropped below 42%. Our
      findings suggested that the ischemic threshold for SjvO2 in patients with severe
      head injury is 45%, below which secondary brain damage occurred.

PMID- 16463823
TI  - Estimated cerebral respiratory quotient and arteriovenous differences of CO2 in
      the ultra early detection of global ischemia in severe head injury.
AB  - The specificity of jugular bulb saturation (SjO2) and arteriovenous oxygen
      difference (AVDO2) to detect global cerebral ischemia remains controversial. An
      absolute increase in the arteriovenous difference of carbon dioxide tension
      (AVDpCO2) and, more specifically, the estimated respiratory quotient (eRQ =
      AVDpCO2/AVDO2) may indicate anaerobic CO2 production. We compared these variables
      with SjO2 to predict global cerebral ischemia. We selected 36 patients from a
      cohort of 69 consecutive patients suffering from severe traumatic brain injury.
      All patients had jugular bulb sampling within 6 hours after injury. Brain death
      at 48 hours was used as a surrogate index of irreversible ischemia to build a
      receiver operating characteristics (ROC) curve analysis. The mean (+/- standard
      deviation) eRQ in the 13 patients who died early (3.7 +/- 3.2 mmHg/ml/dl) was
      higher than the survivors (1.78 +/- 0.45 mmHg/ml/dl, P = 0.03). There was no
      differences in SjO2 between groups. The area under the ROC curves for eRQ, but
      not that of AVDpCO2, was greater (P = 0.04) than that of SjO2. The eRQ, more than
      AVDpCO2, appears to be a potentially more informative index of global cerebral
      ischemia than SjO2.

PMID- 16463824
TI  - Linear correlation between stable intracranial pressure decrease and regional
      cerebral oxygenation improvement following mannitol administration in severe
      acute head injury patients.
AB  - OBJECTIVES: We investigated the relationship between stable decrease in
      intracranial pressure (ICP) following mannitol administration and variations in
      regional oxygenation (PtiO2) in severe traumatic brain injured (STBI) patients.
      METHODS: Fourteen STBI patients (Glasgow Coma Scale score < or = 8) admitted to
      the neurointensive care unit during a 12-month period were studied.
      Multiparameter data, including parenchymal tissue oxygen (PtiO2) and carbon
      dioxide tension, cerebral perfusion pressure, mean arterial pressure;
      temperature, pH and pressure reactivity index were measured. Point values from 53
      mannitol administrations were extracted every five seconds and divided into five
      consecutive 30-minute epochs. Mean values and trends were identified.
      Postadministration epoch with maximum decrease in ICP was selected along with the
      means of the corresponding variables. These data were compared with baseline to
      derive the delta values. Mean deltaICP was then compared with deltaPtiO2 in each
      patient using linear correlation. FINDINGS: In patients with ICP0 > 20 mmHg
      (group A), PtiO2 increased in 69.6% of samples, whereas in group B (ICP0 < 20
      mmHg), PtiO2 increased in only 50% of the samples. There was a significant
      negative correlation between mean deltaICP and deltaPtiO2 in both groups; Group
      A: r = -0.79 (P = 0.01); Group B: r = -0.92 (P = 0.01). CONCLUSIONS: There is a
      strong negative correlation between stable decrease in ICP following mannitol
      administration and improvement in regional oxygenation around the peri
      contusional area. The data suggest a potentially favourable interaction between
      mannitol therapy and cerebral internal milieu in STBI patients.

PMID- 16463825
TI  - Brain tissue oxygen (PtiO2): a clinical comparison of two monitoring devices.
AB  - BACKGROUND: We investigated the difference between two commercially available
      sensors for continuous monitoring of brain tissue oxygen (PtiO2). One is a single
      parameter probe for PtiO2 monitoring (Licox), the other is a multiparamter sensor
      (Neurotrend) further including measurement of brain temperature, pH, and partial
      pressure of tissue carbon dioxide. METHODS: In seven patients after subarachnoid
      hemorrhage or traumatic brain injury continuous monitoring of PtiO2 was performed
      simultaneously using Licox and Neurotrend. FINDINGS: Mean PtiO2 was generally
      lower when assessed by the Neurotrend, as compared with the Licox (Licox 27.7
      mmHg vs. Neurotrend 20.9 mmHg; P = 0.028). The amplitude of PtiO2 elevations
      during ventilation with 100% oxygen was higher with the Licox, but this did not
      reach statistical significance (Licox 55.2 mmHg vs. Neurotrend 50.2 mmHg, P =
      0.082). Regarding clinical stability of the sensors, only one Neurotrend sensor
      provided valid function over the desired monitoring period. Five Neurotrend
      sensors dislocated or broke and one sensor did not show any function after
      insertion. No malfunction occurred with the Licox sensors. CONCLUSIONS: Our
      results suggest that PtiO2 might be lower when assessed by the Neurotrend sensor.
      The clinical stability of the Neurotrend sensor was of concern and allowed
      monitoring in one of seven patients over the desired monitoring period of several
      days only.

PMID- 16463826
TI  - Extracellular amino acid changes in patients during reversible cerebral
      ischaemia.
AB  - This study investigated the changes in extracellular chemistry during reversible
      human cerebral ischaemia. Delayed analysis was performed on samples taken from a
      subgroup of patients during aneurysm surgery previously reported. Frozen
      microdialysis samples from 14 patients who had all undergone temporary clipping
      of the ipsilateral internal carotid artery (ICA) were analysed for another 15
      amino acids with HPLC and for glycerol with CMA-600. Changes were characterised
      according to whether cerebral tissue oxygen pressure (PBO2) decreases were brief
      or prolonged. Brief ICA clipping (maximum duration of 16 minutes) in 11 patients
      was not associated with changes in amino acids or glycerol. Cerebral ischaemia,
      defined by a PBO2 decrease below 1.1 kPa for at least 30 minutes during ICA
      occlusion, occurred in 3 patients. None of whom developed an infarct in the
      monitored region. This prolonged reversible ischaemia was associated with
      transient delayed increases in gamma-amino butyric acid (GABA) as well as
      glutamate and glycerol, each by two-to-three folds. This study demonstrates
      detectable transient increases in human extracellular glutamate, GABA and
      glycerol during identified periods of reversible cerebral ischaemia, maximal 30
      60 minutes after onset of ischaemia, but not in other amino acids detected by
      HPLC.

PMID- 16463827
TI  - Cerebral metabolism and intracranial hypertension in high grade aneurysmal
      subarachnoid haemorrhage patients.
AB  - We evaluated the effect of intracranial hypertension on cerebral metabolism in
      patients with high grade aneurysmal subarachnoid hemorrhage (SAH) using bedside
      cerebral microdialysis (MD). Thirty-six patients with SAH were studied and
      classified into two groups (intracranial pressure, ICP > 20 mmHg, n = 25) and
      (ICP < 20 mmHg, n = 11). ICP was monitored hourly using an intraventricular
      drainage (n = 36). The MD catheter was placed after aneurysm clipping into the
      vascular territory of interest and was perfused with Ringer's solution (0.3
      microl/min). The MD samples were collected hourly for measurements of glucose,
      lactate, and glutamate (CMA 600, Sweden). Lactate/pyruvate ratio was also
      calculated. To calculate group specific differences, the 24 hours median values
      of the first 7 days after SAH were compared. Differences were considered
      statistically significant at P < 0.05. Patient groups were comparable for age,
      severity of SAH, Fisher's grade and duration of MD sampling. In patients with ICP
      > 20 mmHg from day 1 to 7 after SAH, extracellular concentrations of glucose were
      significantly lower, while the lactate/ pyruvate ratio was higher compared to SAH
      patients with normal ICP values. The differences between groups in glutamate
      levels was only significant on day 1 after SAH due to high inter-individual
      differences. We concluded that intracranial hypertension in associated with an
      anaerobic cerebral metabolism indicated cerebral ischemia in high grade SAH
      patients.

PMID- 16463828
TI  - Effect of ischemic preconditioning on brain tissue gases and pH during temporary
      cerebral artery occlusion.
AB  - Previous studies have demonstrated that a brief period of ischemia protect
      against subsequent severe ischemic insults to the brain, i.e. preconditioning. We
      evaluated the effects of ischemic preconditioning, produced by 2 min proximal
      temporary artery occlusion, on brain tissue gases and acidity during clipping of
      cerebral aneurysm. Twelve patients with aneurysmal subarachnoid hemorrhage were
      recruited. All patients received standard anesthetics. After craniotomy, a
      calibrated multiparameter catheter was inserted to measure oxygen (PtO2) tension,
      carbon dioxide (PtCO2) tension and pH (pHt) in tissue at risk of ischemia during
      temporary artery occlusion. In patients assigned to the preconditioning group,
      proximal artery was occluded initially for 2 min and was allowed to reperfuse for
      30 min. All patients underwent cerebral artery occlusion for clipping of
      aneurysm. The rate of change in PtO2, PtCO2 and pHt after artery occlusion were
      compared between groups using unpaired t test. Baseline brain tissue gases and
      pHt were similar between groups. Following artery occlusion, the decline in PtO2
      and pHt were significantly slower in the preconditioning group compared with the
      routine care group. These results suggested that ischemic preconditioning
      attenuates tissue hypoxia during subsequent artery occlusion. Brief occlusion of
      the proximal artery may be a simple maneuver for brain protection during complex
      cerebrovascular surgery.

PMID- 16463829
TI  - Changes in cerebral hemodynamics and cerebral oxygenation during surgical
      evacuation for hypertensive intracerebral putaminal hemorrhage.
AB  - OBJECTIVES: The aim of this study was to evaluate the changes in cerebral
      hemodynamics, tissue oxygenation and blood flow before and after surgery for
      spontaneous intracerebral hematomas. METHODS: Eleven patients who underwent
      surgical decompression of spontaneous putaminal hematoma were studied.
      Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue
      oxygen (PtiO2), and carbon dioxide tensions (PtiCO2), brain pH and regional
      cerebral blood flow (rCBF) were recorded prior to removing the bone flap and then
      on skin closure on completion of the operation. RESULTS: Following surgical
      decompression, mean ICP decreased significantly (P < 0.05); mean CPP, PtiO2,
      brain pH and rCBF improved although the changes were not significant. CONCLUSION:
      Surgical decompression for spontaneous intracerebral hematomas leads to
      significant reductions in ICP. This is accompanied by improvements in CPP, PtiO2
      and rCBF in the penumbra.

PMID- 16463830
TI  - Open lung ventilation in neurosurgery: an update on brain tissue oxygenation.
AB  - Recently, we showed the feasibility of ventilating neurosurgical patients with
      acute intracranial pathology and concomitant acute respiratory distress syndrome
      (ARDS) according the so-called Open Lung approach. This technique consists of low
      tidal volume, elevated positive expiratory pressure (PEEP) level and initial
      recruitment maneuvers to open up collapsed alveoli. In this report, we focus on
      our experience to guide recruitment with brain tissue oxygenation (pbrO2) probes.
      We studied recruitment maneuvers in thirteen patients with ARDS and acute brain
      injury such as subarachnoid hemorrhage and traumatic brain injury. A pbrO2 probe
      was implanted in brain tissue at risk for hypoxia. Recruitment maneuvers were
      performed at an inspired oxygen frcation (FiO2) of 1.0 and a PEEP level of 30 40
      cmH2O for 40 seconds. The mean FiO2 necessary for normoxemia could be decreased
      from 0.85 +/- 0.17 before recruitment to 0.55 +/- 0.12 after 24 hours, while mean
      PbrO2 (24.6 mmHg before recruitment) did not change. At a mean of 17 minutes
      after the first recruitment maneuver, PbrO2 showed peak a value of 35.6 +/- 16.6
      mmHg, reflecting improvement in arterial oxygenation at an FiO2 of 1.0. Brain
      tissue oxygenation monitoring provides a useful adjunct to estimate the effects
      of recruitment maneuvers and ventilator settings in neurosurgical patients with
      acute lung injury.

PMID- 16463831
TI  - Magnesium sulfate for brain protection during temporary cerebral artery
      occlusion.
AB  - We evaluated the effects of magnesium sulfate on brain tissue oxygen (PtO2)
      tension, carbon dioxide (PtCO2) tension and pH (pHt) in patients undergoing
      temporary artery occlusion for clipping of cerebral aneurysm. We studied 18
      patients with aneurysmal subarachnoid hemorrhage. All patients received standard
      anesthetics using target controlled infusion of propofol (3 microg/ml) and
      remifentanil (10 ng/ml). After craniotomy, a calibrated multiparameter sensor
      (Neurotrend, Diametrics Medical, Minneapolis, MN) was inserted to measure PtO2,
      PtCO2 and pHt in tissue at risk of ischemia during temporary artery occlusion.
      Patients were then randomly allocated to receive either intravenous saline or
      magnesium 20 mmol over 10 min followed by an infusion 4 mmol/h. Plasma magnesium
      concentration, brain tissue gases and pHt were determined at baseline, 30 min
      after study drug infusion and 4 min after temporary clipping. Data were analyzed
      by factorial ANOVA with repeated measures. Intergroup difference was compared
      with unpaired t test. P value < 0.05 was considered significant. Patient
      characteristics, baseline brain tissue gases and pHt did not differ between
      groups. Magnesium infusion increased PtO2 by 34%. Following temporary artery
      occlusion, PtO2 and pHt decreased and PtCO2 increased in both groups. However,
      tissue hypoxia was less severe and the rate of PtO2 decline was slower in the
      magnesium group. Our data suggested that magnesium enhances tissue oxygenation
      and attenuates hypoxia during temporary artery occlusion.

PMID- 16463832
TI  - Monitoring of autoregulation using intracerebral microdialysis in patients with
      severe head injury.
AB  - We evaluated the performance of continuous intracerebral microdialysis to
      indicate the autoregulatory reserve in 36 severely head-injured patients. All
      patients received standard treatment with intracranial pressure (ICP) monitoring.
      A microdialysis probe was placed in the frontal cortex anterior to the ICP
      catheter. Perfusate was collected frequently and extracellular concentration of
      glutamate was measured online using enzymatic method. Autoregulatory index was
      calculated by comparing glutamate concentration with CPP using Pearson's
      correlation. A correlation coefficient (r) < 0.5 is considered as loss of
      autoregulation, whereas r values approach 0 indicate preserved autoregulation.
      The change of autoregulatory status over time was correlated with outcome at 6
      months. Three patterns of autoregulatory profiles were identified. Patients with
      intact autoregulation had satisfactory outcome. Transient impairment of
      autoregulation may result in favorable outcome if patients responded to
      treatment. However, persistent loss of autoregulation was associated with poor
      outcome (P < 0.001). The correlation between extracellular glutamate
      concentration (by microdialysis) and CPP is a useful index of autoregulation in
      head-injured patients. It predicts clinical outcome and may be used to guide
      therapy.

PMID- 16463833
TI  - Improvement of brain tissue oxygen and intracranial pressure during and after
      surgical decompression for diffuse brain oedema and space occupying infarction.
AB  - BACKGROUND: We evaluated the perioperative and intraoperative changes of
      intracranial pressure (ICP) and partial pressure of brain tissue oxygen (PtiO2)
      after decompressive craniectomy in patients with diffuse brain oedema and space
      occupying infarction. METHODS: Ten patients suffering from medically intractable
      raised intracranial pressure (ICP) were included. The underlying diseases and
      causes for elevated ICP were diffuse brain oedema after subarachnoid haemorrhage
      (n = 3) and head injury (n = 3), or space occupying infarction of the middle
      cerebral artery territory due to vasospasm after SAH (n = 4). Continuous
      perioperative and intraoperative monitoring of PtiO2 and ICP was performed at the
      side of decompression. FINDINGS: ICP and PtiO2 improved significantly in a
      uniform pattern during bone flap removal and dura opening, irrespective of the
      underlying disease (mean ICP from 52 mmHg to 8 mmHg, mean PtiO2 from 9 mmHg to 25
      mmHg). ICP, PtiO2, and cerebral perfusion pressure were further improved in the
      subsequent 12 hours after surgery, as compared to the preoperative 12 hours.
      CONCLUSIONS: Decompressive craniectomy seems to be a successful option in the
      treatment of intractable intracranial hypertension with associated cerebral
      hypoxia. These positive effects may last for several hours after the procedure
      irrespective of the underlying disease.

PMID- 16463834
TI  - Clinic investigation and logistic analysis of risk factors of recurrent
      hemorrhage after operation in the earlier period of cerebral hemorrhage.
AB  - Objective of this study was to investigate the incidence, time, location,
      prevention, treatment and risk factors of recurrent hemorrhage in the earlier
      period of cerebral hemorrhage after operation. Three hundred and twenty two
      patients with operations in the earlier period of cerebral hemorrhage were
      analyzed retrospectively. The clinical data of hemorrhage and recurrent cerebral
      hemorrhage groups were compared and statistically analyzed. Logistic regression
      analysis was applied to evaluate the function of possible factors leading to
      recurrent hemorrhage after operation. The incidence of recurrent hemorrhage was
      21.4% in the earlier period of cerebral hemorrhage after operation. When the
      operation was performed after cerebral hemorrhage within 6 h, 6-12 h and 12-24 h,
      the incidence of recurrent hemorrhage after operation were 43.1%, 20.9%, 3.6%
      respectively. With regard to time of recurrent hemorrhage, the incidence was 3.1%
      within 12 h after operation, 15.5% between 12-24 h and just 2.8% after 24 h. Site
      of hemorrhage was in the basal ganglion in 92.6% of the cases. Mono-agent
      logistic analysis displayed that there is a significant correlation between high
      diastolic blood pressure, fluctuation of blood pressure after operation, taking
      anti-coagulant drugs for a long time, site of hemorrhage, difficult or not
      thorough hemostasis during operation and recurrent hemorrhage (p < 0.01).
      Multiple linear logistic regression analysis has shown that a remarkable
      diastolic blood pressure and fluctuation of blood pressure after operation are
      risk factors for recurrent hemorrhage. Their OR value were 10.32, 7.234. From
      this it is concluded that the incidence of recurrent cerebral hemorrhage after
      operation in the earlier period is 21.4%, which must never be ignored. The time
      period of 24 h after operation is a stage of high risk. Maintaining diastolic
      blood pressure below 85 mmHg and steadily controlling the pressure after
      operation are of great importance for prevention of recurrent cerebral
      hemorrhage.

PMID- 16463835
TI  - Cerebral blood flow augmentation in patients with severe subarachnoid
      haemorrhage.
AB  - Following aneurysmal subarachnoid haemorrhage (SAH), cerebral blood flow (CBF)
      may be reduced, resulting in poor outcome due to cerebral ischaemia and
      subsequent stroke. Hypertonic saline (HS) is known to be effective in reducing
      intracranial pressure (ICP). We have previously shown a 20-50% increase in CBF in
      ischaemic regions after intravenous infusion of HS. This study aims to determine
      the effect of HS on CBF augmentation, substrate delivery and metabolism.
      Continuous monitoring of arterial blood pressure (ABP), ICP, cerebral perfusion
      pressure (CPP), brain tissue oxygen (PbO2), middle cerebral artery flow velocity
      (FV), and microdialysis was performed in 14 poor grade SAH patients. Patients
      were given an infusion of 23.5% HS, and quantified xenon computerised tomography
      scanning (XeCT) was carried out before and after the infusion in 9 patients. The
      results showed a significant increase in ABP, CPP, FV and PbO2, and a significant
      decrease in ICP (p < 0.05). Nine patients showed a decrease in lactate-pyruvate
      ratio at 60 minutes following HS infusion. These results show that HS safely and
      effectively augments CBF in patients with poor grade SAH and significantly
      improves cerebral oxygenation. An improvement in cerebral metabolic status in
      terms of lactate-pyruvate ratio is also associated with HS infusion.

PMID- 16463836
TI  - Evidence for the importance of extracranial venous flow in patients with
      idiopathic intracranial hypertension (IIH).
AB  - Idiopathic intracranial hypertension (IIH) is characterized by increased ICP
      without evidence for intracranial mass lesion. Although the pathogenesis remains
      unknown, some association was found with intracranial venous thrombosis. To our
      knowledge, the extracranial venous drainage was not systematically evaluated in
      these patients. This study compared extracranial cerebral venous outflow in eight
      IIH patients and eight control subjects using magnetic resonance (MR) Venography
      and flow measurements. In addition, the study identified extracranial factors
      that affect cerebral venous drainage. In six of the IIH patients, either complete
      or partial functional obstruction of the internal jugular veins (IJVs) coupled
      with increased venous outflow through secondary venous channels was documented.
      On average, a four-fold increase in mean venous flow rate through the epidural
      and/or vertebral veins was measured in IIH patients compared with the healthy
      subjects. In one of the healthy subjects, intracranial venous outflow was studied
      also during external compression of the IJVs. Over 40% of the venous outflow
      through the IJVs shifted to the epidural veins and intracranial pressure,
      measured noninvasively by MRI, increased from 7.5 to 13 mmHg. Findings from this
      study suggest that increased ICP in some IIH patients could be associated with
      increased extracranial resistance to cerebral venous outflow.

PMID- 16463837
TI  - Subdural intracranial pressure, cerebral perfusion pressure, and degree of
      cerebral swelling in supra- and infratentorial space-occupying lesions in
      children.
AB  - To our knowledge comparative studies of intracranial pressure (ICP) and degree of
      cerebral swelling during craniotomy for supratentorial or infratentorial space
      occupying lesion in children are not available. In this prospective study
      subdural ICP, cerebral perfusion pressure (CPP), dural tension, and the degree of
      cerebral swelling were analysed in supine and prone positioned children subjected
      to craniotomy for space occupying lesions. MATERIAL AND METHOD: 48 children with
      space occupying tumours were subjected to either isoflurane/nitrous oxide
      50%/fentanyl (n = 22) or propofol/fentanyl/air/oxygen (n = 26). 25 children were
      operated supratentorially in supine position, while 23 patients were operated
      infratentorially in the prone position. Subdural ICP, mean arterial blood
      pressure (MABP), and CPP were measured just before opening of the dura. Dural
      tension was estimated before opening of dura, and the degree of cerebral swelling
      was estimated after opening of dura. RESULTS: The age and weight of children
      anaesthetised with isoflurane in the prone position were significantly lower than
      the propofol anaesthetised groups. No significant inter-group differences as
      regards tumour size, midline shift, rectal temperature, MABP or PaCO2 were found.
      ICP in prone positioned children averaged 16.9 mm Hg against 9.0 mm Hg in supine
      positioned children (p < 0.001). In prone positioned children the dura was
      significantly tenser, and the degree of brain swelling after opening of dura was
      significantly more pronounced. No significant difference as regard ICP was
      disclosed when isoflurane/nitrous oxide/fentanyl and propofol/ fentanyl
      anaesthetized children were compared, but MABP and CPP were significantly lower
      in isoflurane anaesthetised children. CONCLUSION: In children with cerebral
      tumours ICP is higher, and the degree of cerebral swelling more pronounced in the
      prone-compared with supine positioned children. Choice of anaesthesia did not
      influence ICP, but CPP was significantly lower during isoflurane anaesthesia.

PMID- 16463838
TI  - The role of noninvasive monitoring of cerebral electrical impedance in stroke.
AB  - OBJECTIVE: To explore the change regularity of cerebral electrical impedance
      (CEI) in the healthy people and patients with intracerebral hemorrhage (ICH) and
      ischemic stroke. METHODS: CEI of 100 healthy volunteers, 52 patients with ICH and
      33 patients with ischemic stroke was measured by noninvasive Brain-Edema Monitor.
      The results of perturbative index (PI) converted from CEI were compared with the
      volume of infarction, hematoma and surrounding edema, which calculated by image
      analyzing system according to MRI or CT. RESULTS: In the normal groups, PI in the
      left and right sides of cerebral hemispheres was respectively 7.76 +/- 0.75 and
      7.79 +/- 0.58, and there was no significant difference between the two sides (P >
      0.05). In the patients with ICH, PI in the hematoma side decreased and was lower
      than the other side, and then increased gradually, finally exceeded that of the
      other side. The average "cross" time was (16.25 +/- 8.96) h. It showed that the
      volume of hematoma was no obvious change before and after the "cross" time
      [(31.25 +/- 21.59) vs (37.59 +/- 27.57)] (P > 0.05). However, the volume of peri
      hematoma edema was significantly larger after the "cross" time than before the
      "cross" time [(26.35 +/- 13.96) vs (14.68 +/- 5.30)] (P < 0.05). There was a
      positive correlation between the PI of hematoma side and the volume of peri
      hematoma edema (r = 0.8811, P < 0.01). In the patients with arterothrombotic
      cerebral infarction, PI in the infarct side had a positive correlation with the
      volume of infarction (r = 0.8496, P < 0.01). CONCLUSIONS: CEI is a stable
      physical parameter reflecting the electrical character of human brain tissue. It
      is useful for monitoring edema and hematoma in stroke.

PMID- 16463839
TI  - The effect of subarachnoid sodium nitroprusside on the prevention of vasospasm in
      subarachnoid haemorrhage.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of preventive and
      therapeutic use of subarachnoid sodium nitroprusside (SNP) administration in
      patients with non-traumatic subarachnoid haemorrhage (SAH). METHODS: All
      consecutive adult patients admitted in the period 2000-2003 with SAH, Hunt-Hess
      grade I-IV, indicated for neurosurgical intervention, were enrolled in the study.
      In the postoperative period they were treated with mechanical ventilation and
      triple H protocol with nimodipine. Subarachnoid preventive SNP was administred in
      initial dose of 1 mg by catheter inserted into basal cisterns during the
      neurosurgical procedure. The timing of following dosage was directed by the
      changes of respiratory parameters of brain tissue in the region of interest by
      multiparameter sensor (Codman Neurotrend) and findings of blood flow velocity on
      the level of circle of Willis were measured by transcranial doppler
      ultrasonography (TCD). RESULTS: 17 patients were enrolled to study. All patients
      survived. No brain infarction developed. The increase blood flow velocity was
      found in three patients. CONCLUSION: Preventive subarachnoid use of SNP in
      combination with multimodal monitoring might be a possible preventive strategy.
      Its efficacy has to be proved on a greater group of patients in the future. The
      therapeutical use of SNP requires an increase in application rate.

PMID- 16463840
TI  - Mitochondrial injury measured by proton magnetic resonance spectroscopy in severe
      head trauma patients.
AB  - The aim of this study was to evaluate the extent of mitochondrial injury by
      assessing N-Acetyl-Aspartate by MR spectroscopy in head injured patients and
      relating the extent of mitochondrial injury to outcome. The study population (n =
      15) consisted of head injured patients (GCS < 8) in whom legal consent was
      obtained for MRS studies. Studies were performed on a 1.5 Tesla Vision/Siemens
      system. Size of Voxel equaled 8 cm3 with location determined from T1 images.
      Voxels were positioned adjacent to the lesion and in the contralateral hemisphere
      for focal and bilateral for diffuse. Mitochondrial impairment was considered as
      percent reduction in NAA/ Cr ratio compared to matched controls. Mitochondrial
      impairment gradually increases soon after injury reaching a nadir at 10 days.
      Subsequently, mitochondria recover in patients with favorable outcome, but
      remains impaired in patients with poor outcome. The prognostic value of NAA/Cr to
      assist in management and also to serve as a surrogate endpoint for clinical
      trials appears promising.

PMID- 16463841
TI  - Cerebral blood flow in mean cerebral artery low density areas is not always
      ischemic in patients with aneurysmal subarachnoid hemorrhage--relationship with
      neurological outcome.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) can be complicated by reduction of
      regional cerebral blood flow (rCBF) from large conductance vessels leading to
      focal edema appearing as an area of hypoattenuation on CT. In this study we
      included 29 patients with SAH due to aneurysmal rupture, having 36 CT low density
      areas within the middle cerebral artery territory in whom a total of 56 Xenon-CT
      (Xe-CT) studies were performed. Collectively, we evaluated 70 hypoattenuated
      areas. rCBF levels were measured in two different regions of interest drawn
      manually on the CT scan, one in the low density area and the other in a
      corresponding contralateral area of normal-appearing brain tissue. In the low
      density area (22.6 +/- 22.7 ml/100 gr/min) rCBF levels were significantly lower
      than in the contralateral area (32.8 +/- 17.1 7 ml/100 gr/min) (p = 0.0007). In
      the injured areas deep ischemia (CBF < 6 ml/ 100 g/min) was present in only 25.7%
      of Xe-CT studies, suggesting that hypodense areas are not always ischemic,
      whereas in 43.7% of the lesions/Xe-CT studies we found hyperemic values. Patients
      with a better outcome had hyperemic lesions, suggesting brain tissue recovery in
      injured areas.

PMID- 16463842
TI  - Cerebral blood flow mapping in two different subtypes of intraparenchymal
      hemorrhagic traumatic lesions.
AB  - The pathogenesis and the viability of edematous tissue may be different in
      traumatic hematomas and traumatic contusions. We tested the hypothesis that
      mapping of regional Cerebral Blood Flow (rCBF) was different in these two
      subtypes of traumatic intraparenchymal lesions. We evaluated rCBF by means of
      Xenon-enhanced computerized tomography (Xe-CT) in 59 traumatic intracerebral
      lesions from 43 patients with severe head injury. One-hundred-nine intracerebral
      lesions/Xe-CT CBF measurements were obtained. The rCBF was measured in the
      hemorrhagic core, in the intralesional oedematous low density area and in a 1 cm
      rim of apparently normal perilesional parenchyma of both lesion subtypes. Not
      statistically significant lower rCBF levels were found in the edematous area of
      traumatic contusions. In traumatic hematomas rCBF levels were lower in the core
      than in the low density area, suggesting that rCBF in edematous area is
      marginally involved in the initial traumatic injury and that edema is probably
      influenced by the persistence of the hemorrhagic core. Conversely, in the
      traumatic contusions a difference in rCBF values was found between core, low
      density area and perilesional area, indicating that rCBF of the low density area
      is related to a concentrical distribution of the initial injury.

PMID- 16463843
TI  - Glucose metabolism in traumatic brain injury: a combined microdialysis and [18F]
      2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) study.
AB  - Following traumatic brain injury, as a consequence of ionic disturbances and
      neurochemical cascades, glucose metabolism is affected. [18F]-2-Fluoro-2-deoxy-D
      glucose (FDG) Positron Emission Tomography (FDG-PET) provides a measure of global
      and regional cerebral metabolic rate of glucose (rCMRglc), but only during the
      time of the scan. Microdialysis monitors energy metabolites over extended time
      periods, but only in a small focal volume of the brain. Our objective in this
      study is to assess the association of parameters derived from these techniques
      when applied to patients with traumatic brain injury. Eleven sedated, ventilated
      patients receiving intracranial pressure monitoring and managed using
      Addenbrooke's Neurosciences Critical Care Unit protocols were monitored.
      Dialysate values for glucose, lactate, pyruvate, and glutamate, and the lactate
      to glucose (L/G), lactate to pyruvate (L/P) and pyruvate to glucose (P/G) ratios
      were determined and correlated with rCMRglc. FDG-PET scans were performed within
      24 hours (five patients), or between 1 and 4 days (two patients) or after 4 days
      (six patients). Two patients were rescanned 4 and 7 days after their initial
      scan. A 20 mm region of interest (ROI) was defined on co-registered CT scan on
      two contiguous slices around the microdialysis catheter. Mean (+/-sd) for rCMRglc
      was 19.1 +/- 5.5 micromol/100 g/min, and the corresponding microdialysis values
      were: glucose 1.4 +/- 1.4 mmol/ L; lactate 5.3 +/- 3.6 mmol/L; pyruvate 164.1 +/-
      142.3 micromol/L; glutamate 15.0 +/- 14.7 micromol/L; L/G 11.0 +/- 16.0; L/P 27.3
      +/- 7.9 and P/G 381 +/- 660. There were significant relations between rCMRglc and
      dialysate lactate (r = 0.58, P = 0.04); pyruvate (r = 0.57, P = 0.04), L/G (r =
      0.55, P = 0.05), and the P/G (r = 0.56, P = 0.05) but not between rCMRglc and
      dialysate glucose, L/P or glutamate in this data set. The results suggest that
      increases in glucose utilization as assessed by FDG-PET in these patients albeit
      in mainly healthy tissue are associated with increases in dialysate lactate,
      pyruvate, L/G and the P/G ratio perhaps indicating a general rise in metabolism
      rather than a shift towards non-oxidative metabolism. Further observations are
      required with regions of interest (microdialysis catheters positioned) adjacent
      to mass lesions notably contusions.

PMID- 16463844
TI  - Postoperative changes in SPECT-rCBF in hydrocephalus.
AB  - OBJECTIVES: We investigated the effect of shunt surgery in patients with Normal
      Pressure Hydrocephalus (NPH) using Single Photon Emission Computerised Tomography
      (SPECT). MATERIALS & METHODS: Thirteen patients diagnosed with NPH were assessed
      clinically and using (99m Tc)-SPECT and MRI both pre- and post-operatively.
      Regions of interest were placed manually on T2 MRI and transferred to co
      registered SPECT. Differences between pre- and post-operative cerebellum
      normalised regional cerebral blood flow (rCBF) were calculated and analysed in
      relation to clinical findings represented by a new disability scale. RESULTS: The
      patients presented initially with 50 +/- 30% disability score and improved
      following the surgery by 6 +/- 10% (p = 0.1). We did not observe any significant
      rCBF changes in the whole group of patients (overall rCBF difference = -0.3%, p =
      0.4). Some improvement was in basal frontal lateral cortex, basal ganglia and
      thalamus (+5%, p = 0.08 to 0.2). Patients with <30% disability score initially (N
      = 4) had a reversed pattern of changes compared to those with more symptoms (p <
      0.05). CONCLUSIONS: The small patient sample failed to show significant changes
      in rCBF due to NPH or surgery. There is indication that in patients with good
      initial clinical presentation there is little space for relevant clinical
      improvement and increase in rCBF.

PMID- 16463845
TI  - Dynamic susceptibility contrast-enhanced perfusion MR imaging in late radiation
      induced injury of the brain.
AB  - The objective of the study was to evaluate radiation-induced cerebral injury on
      dynamic susceptibility contrast-enhanced (DSCE) perfusion MR imaging and study
      its relationship with morphological severity and disease progression. Thirty-one
      patients with known radiation injury to the temporal lobes where studied.
      Gradient and spin-echo T2-weighted, gadolinium-enhanced T1-weighted and DSCE
      perfusion MR imaging were obtained in the coronal plane through the anterior
      temporal lobe. Regions of interest where selected in the anterior temporal lobes
      and the superior frontal lobe as control for analysis of perfusion parameters.
      The mean transit time (MTT) was prolonged in both the High Dose Zone (HDZ)
      receiving from two-thirds to the total dose of 66-71.2 Gy, and the Intermediary
      Dose Zone (IDZ) receiving up to 87% of the total dose. The HDZ but not the IDZ
      showed a low relative cerebral blood volume (rCBV) and relative cerebral blood
      flow index (rCBFi). The rCBV and rCBFi were significantly lower in both HDZ and
      LBZ in temporal lobes with severe lesions compared to the temporal lobes with
      mild lesions but there was no significant difference in bolus transit parameters.
      The rCBV and rCBFi were significantly lower in both HDZ and IDZ of the swollen
      temporal lobes compared to those without swelling. It was concluded that DSCE
      perfusion MR imaging demonstrated a derangement in perfusion in radiation-induced
      cerebral injury in rCBV, rCBFi and MTT, which were related to the severity of the
      radiation-induced injury and the dose of irradiation delivered.

PMID- 16463846
TI  - MRI study of cerebral blood flow and CSF flow dynamics in an upright posture: the
      effect of posture on the intracranial compliance and pressure.
AB  - Postural related changes in cerebral hemodynamics and hydrodynamics were studied
      using Magnetic Resonance Imaging (MRI) measurements of cerebral blood flow and
      cerebrospinal fluid (CSF) flow dynamics. Ten healthy volunteers (mean age 29 +/-
      7) were studied in supine and upright (sitting) postures. A Cine phase-contrast
      MRI technique was used to image the pulsatile blood flow to the brain, the venous
      outflow through the internal jugular, epidural, and vertebral veins, and the bi
      directional CSF flow between the cranium and the spinal canal. Previously
      published analyses were applied to calculate and compare total cerebral blood
      flow (TCBF), intracranial compliance and pressure in both postures. A lower (12%)
      mean TCBF was measured in the upright position compared to supine position. A
      considerable smaller amount of CSF flow between the cranium and the spinal canal
      (58%), a much larger intracranial compliance (a 2.8-fold increase), and a
      corresponding decrease in the MRI-derived ICP were also measured in the sitting
      position. These changes suggest that the increased cerebrovascular and
      intracranial compliances in the upright posture are primarily due to reduced
      amounts of blood and CSF residing in their respective intracranial compartments
      in the upright position. This work demonstrates the ability to quantify
      neurophysiologic parameters associated with regulation of cerebral hemodynamics
      and hydrodynamics from dynamic MR imaging of blood and CSF flows.

PMID- 16463848
TI  - Relationship between total cerebral blood flow and ICP measured noninvasively
      with dynamic MRI technique in healthy subjects.
AB  - Cerebral blood flow and ICP are important neurophysiologic parameters known to be
      affected by pathology and by trauma. Limited data on the relationship between
      these parameters following head trauma is inconsistent with regard to whether
      these parameters are correlated. Data on the relationship between these
      parameters in the healthy state is not readily available due to a lack of
      noninvasive means to measure these important parameters. A recently developed
      noninvasive MRI-based method for simultaneous measurement of total cerebral blood
      flow and intracranial pressure was applied to establish the relationship between
      ICP and TCBF values in healthy subjects. Seventy-one simultaneous measurements of
      CBF and ICP were obtained from 23 healthy young adults. These results
      demonstrated that CBF values span over a much narrower range compared with ICP.
      The relationship between the inter-individual CBF and ICP measurements suggest
      that in the healthy state and in rest these parameters are not correlated.

PMID- 16463847
TI  - Quantitative evaluation of cerebrovascular reactivity in brain tissue by a refill
      kinetic method of transcranial ultrasonic perfusion imaging: a comparison with
      Doppler sonography.
AB  - To confirm the reliability of a refill kinetic method of ultrasonic harmonic
      perfusion imaging (HPI) capable of quantifying separate parameters of
      microvascular blood flow velocity and volume in brain tissue, we evaluated
      acetazolamide (ACZ) cerebrovascular reactivity by transcranial HPI in comparison
      with Doppler sonography (TCD). Methods. HPI during continuous Levovist infusion
      with changing pulsing intervals (t) and TCD time-averaged maximum velocity (TAMX)
      in the middle and posterior cerebral arteries were evaluated before and after ACZ
      administration in 12 patients, 8 without and 4 with a temporal skull defect.
      Plateau value (A) and rise rate (beta) of intensity (I) represented by HPI time
      intensity curves of I(t) = A(1 - e(-beta*t)) were analyzed on the axial
      diencephalic plane. RESULTS: 1) A significantly decreased in proportion to the
      region of interest location depth only in the intact skull cases. 2) Despite
      inter- and intra-individual data scattering, in correspondence with TAMX
      increases after ACZ, significant beta increases were more frequently identified
      than increases of A. CONCLUSIONS: Cerebral vasoreactivity analysis utilizing
      refill kinetics of transcranial HPI can potentially provide separate
      quantification based on microvascular blood velocity and volume (capillary
      patency) with consideration of depth-dependant ultrasound attenuation. This
      should be suitable for bedside evaluation of neurointensive care patients.

PMID- 16463849
TI  - Clinical comparison of tympanic membrane displacement with invasive ICP
      measurements.
AB  - OBJECTIVE: Tympanic membrane displacement (TMD) measurements may be useful in the
      management of patients with hydrocephalus if they can be directly associated with
      measurements of ICP. We have compared TMD measurements using the Marchbanks
      Measurement System with invasive ICP monitoring. METHODS: Twenty-nine patients
      who were undergoing routine invasive monitoring using a Camino fibre optic ICP
      measurement system as part of their clinical management were studied.
      Simultaneous measurements of ICP and TMD in both sitting and supine positions
      were successfully made in thirteen patients. RESULTS: Thirty-nine pairs of
      readings were obtained. The invasive ICP readings varied from 1 to 36 mmHg in the
      supine position and from -12 to +35 mmHg sitting. Corresponding TMD values varied
      from 275 to +277 nL in the supine position and -133 to +466 nL sitting. Linear
      regression showed a significant negative relationship between the two
      measurements (r = -0.57, p = 0.0013). CONCLUSIONS: There is a strong negative
      linear association between mean TMD and invasively measured ICP and this
      relationship is highly significant. Nevertheless, TMD is a poor surrogate for ICP
      in clinical terms because the predictive limits of the linear regression are too
      wide. However, serial intra-patient measurements may be useful to determine
      changes in ICP with time.

PMID- 16463850
TI  - Gravity valves for idiopathic normal-pressure hydrocephalus: a prospective study
      with 60 patients.
AB  - OBJECTIVE: Are hydrostatic valves superior to conventional differential pressure
      shunts in patients with normal-pressure hydrocephalus, with regard to the
      postoperative results of treatment and possible complications? METHODS: From
      September 1997 to January 2002, 60 patients with idiopathic normal-pressure
      hydrocephalus were treated by surgical implantation of hydrostatic valve at the
      Unfallkrankenhaus Berlin. In a prospective study, the clinical examination and a
      CT examination were carried out preoperatively, postoperatively and 1 year after
      the operation. RESULTS: One year after the operation, the clinical picture was
      very good for 33% of the patients, good for 33% and satisfactory or poor for 17%,
      each, of the patients. 3 dislocations (5%) of ventricular or abdominal catheters
      and three valve infections were found as valve-independent. As valve-dependent
      complications, underdrainage was found in 4 patients (7%) and radiological signs
      of overdrainage in 2 patients (3%), while 1 patient (1.7%) showed symptomatic
      over-drainage. CONCLUSION: According to our experience, hydrostatic Dual-switch
      valves Aesulap are superior to conventional differential pressure shunts without
      an additional gravity unit especially with regard to the treatment of patients
      with idiopathic normal-pressure hydrocephalus, concerning both the postoperative
      results and the incidence of possible complications. A clinical improvement can
      be achieved for 83% of such patients.

PMID- 16463851
TI  - The relationship between CSF circulation and cerebrovascular pressure-reactivity
      in normal pressure hydrocephalus.
AB  - OBJECTIVE: Previously, we documented association between CSF circulation and
      transcranial-Doppler derived autoregulation in non-shunted patients suffering
      from hydrocephalus. In the present study we sought to investigate the
      relationship between the resistance to CSF outflow and pressure-reactivity both
      in shunted and non-shunted NPH patients. MATERIAL AND METHODS: Sixty-eight
      patients (47 non-shunted and 21 shunted) with NPH have been examined as a part of
      routine diagnostic procedure. Resistance to CSF outflow (Rcsf) was measured using
      a ventricular constant rate infusion test. Cerebrovascular pressure-reactivity
      was assessed as a moving correlation coefficient (PRx) between coherent 'slow
      waves' of ICP and arterial blood pressure (ABP). This variable has previously
      been demonstrated to correlate with the autoregulation of CBF in patients
      following head injury. Results. In non-shunted patients cerebrovascular pressure
      reactivity (PRx) was negatively correlated with Rcsf (R = -0.5; p < 0.0005). This
      relationship was inverted in shunted patients: a positive correlation between PRx
      and Rcsf was found (R = 0.51; p < 0.03). CONCLUSION: Cerebrovascular pressure
      reactivity is disturbed in patients with normal resistance to CSF outflow,
      suggesting underlying cerebrovascular disease. This result confirms our previous
      finding where transcranial Doppler autoregulation was investigated. After
      shunting the pressure-reactivity strongly depends on shunt functioning and
      deteriorates when the shunt is blocked.

PMID- 16463852
TI  - Evolution of intracranial pressure during the immediate postoperative period
      after endoscopic third ventriculostomy.
AB  - OBJECTIVE: To establish a more accurate indication for endoscopic third
      ventriculostomy (ETV) in patients with noncommunicating hydrocephalus through the
      analysis of the evolution of postoperative mean intracranial pressure (ICPM).
      METHOD: Intracranial pressure (ICP) was recorded overnight during 8-hour periods
      with an intraventricular probe. A personal computer connected to the ICP monitor
      minutely recorded the values of ICP. Twenty-four patients were monitored from day
      1 to day 3 after ETV. The evolution of ICPM was analysed with an ANOVA test for
      repeated measures. The relevance of different factors (age, etiology, size of the
      lesion leading to hydrocephalus, clinical course and outcome) on the evolution of
      ICPM was explored with a two-factor ANOVA. RESULTS: ICPM progressively decreased
      from day 1 to day 3 after ETV (p = 0.03). ICPM on the first postoperative day was
      15.81 +/- 2.04 mm Hg (mean +/- standard error) and 13.43 +/- 1.44 mm Hg on the
      third postoperative day. Different patterns in the evolution of ICPM have been
      detected according to the age of the patient and the clinical course of
      hydrocephalus. CONCLUSION: ICPM progressively decreases after ETV. This pattern
      is not constant. It has been clearly detected in children and in acute forms of
      hydrocephalus.

PMID- 16463853
TI  - Clinical research on monitoring CSFP through lumbar epidural pressure.
AB  - OBJECTIVE: Explore the relationship between lumbar Epidural Pressure (LEDP) and
      CSFP through clinical studies and to determine whether LEDP can represent CSFP.
      METHODS: We selected 150 cases of cerebral diseases at random for this study. A
      special mini transducer was implanted into the lumbar epidural space between the
      third and the 4th lumbar vertebra by means of a No. 18 Touhy needle for
      monitoring of LEDP. In the meantime, a traditional lumbar puncture was made
      between the 4th and the 5th lumbar vertebrae and CSFP, which was taken as the
      standard value, was measured using an ordinary catheter. The transducer was
      adjusted until the LEDP was equal to CSFP and was designated LEDP0. The LEDP0 was
      monitored continuously and was translated into a continuous curve. In each and
      every case, a lumbar puncture was repeated at 24, 48, 72 and 96 hours to obtain
      CSFP for comparison and to explore the relationship between LEDP0 and CSFP. While
      monitoring LEDP0, we observed the variation in pressure when the patient
      breathed, coughed, changed posture, and also if the clinical symptoms changed
      with intracranial hypertension. RESULT: The values of the intracranial pressure
      measured by these two methods were identical. CONCLUSION: LEDP responded to the
      changes of CSFP.

PMID- 16463854
TI  - Evaluation of three new models of hydrocephalus shunts.
AB  - OBJECTIVE: To assess the hydrodynamic properties of three new types of
      hydrocephalus valve. METHODS: Three new constructions have been recently tested
      in the UK shunt Evaluation Laboratory: the magnetically adjustable Strata Valve
      (Medtronic PS Medical), the gravitational Miethke Dual-Switch Valve (Aesculap)
      and the ventriculo-sinus SinuShunt (CSF Dynamics). Pressure-flow performance
      curves were assessed in a minimum of three samples of each valve to study their
      longterm variability, influence of temperature, negative outlet pressure,
      external pressure, presence of pressure pulsations, etc. RESULTS: The operating
      pressure of the Strata Valve can be adjusted magnetically in five steps. This
      Shunt prevents 'siphoning' but is sensitive to external pressure. The Dual Switch
      Miethke Valve is a system of two fixed-pressure ball-on-spring valves with a
      lower opening pressure operating in a horizontal body position and higher when
      vertical. This function is designed to cancel the effect of siphoning related to
      body posture. Both Strata and DSV valves have a low hydrodynamic resistance (less
      than 3 mm Hg/ml/min), and hence they cannot prevent overdrainage related to
      nocturnal vasomotor waves. The SinuShunt has a higher resistance (9 mm
      Hg/(ml/min)) and a lower opening pressure. The valve is intended to drain CSF
      from ventricles to the transverse sinus. CONCLUSION: New shunt technology
      continues to evolve. Laboratory evaluation independent of the manufacturer forms
      an important link between R&D laboratories and clinical practice.

PMID- 16463856
TI  - Guidelines for management of idiopathic normal pressure hydrocephalus: progress
      to date.
AB  - The aim of this project was to develop evidenced based guidelines for the
      diagnosis and management of idiopathic normal pressure hydrocephalus (iNPH). An
      advisory panel consisting of the authors assisted by international experts met on
      several occasions and formulated preliminary guidelines for iNPH managemen. The
      authors developed evidentiary tables based on available literature from 1966 to
      the present. Additional meetings to refine the evidentiary tables and incorporate
      expert opinion when necessary resulted in the development the iNPH guidelines.
      Evidence based guidelines identifying the value of clinical examination, brain
      imaging, Tap Test, CSF drainage, ICP monitoring and Surgical Management in
      diagnosing and treating the iNPH patient were developed. These are the first
      international evidence based guidelines focused on iNPH. Class I data were scant
      and guidelines relied mostly on class II and III evidence. It became clear that
      more prospective randomized studies are needed to resolve some of the
      controversial issues such as iNPH classification and sensitivity of diagnostic
      tests for identifying shunt responsive iNPH.

PMID- 16463855
TI  - The enigma of underdrainage in shunting with hydrostatic valves and possible
      solutions.
AB  - OBJECTIVE: Hydrostatic devices have considerable advantages compared to
      "conventional" differential-pressure-valves concerning overdrainage, but are
      thought to imply a tendency to underdrain or to clog. The aim of this study was
      to evaluate the ability of the hydrostatic gravitational Dual-Switch-Valve (DSV)
      to minimize overdrainage-related complications without increasing the danger of
      underdrainage. RESULTS: In a series of 202 adult patients with different
      etiologies treated with a ventriculo-peritoneal shunt including the hydrostatic
      Dual-Switch-valve (DSV), 21 cases were suspected of suffering from underdrainage.
      Using a new algorithm we were able to differentiate obstruction in 6 patients
      from functional underdrainage in 15 cases, thus we saw an indication to reimplant
      a DSV with a lower opening pressure in the latter. CONCLUSION: The reasons for
      functional underdrainage were multifold in our series, especially the
      intraperitoneal pressure is still a "black box". Despite the ability of the DSV
      to avoid clogging and to minimize overdrainage by its high-pressure-chamber, it
      remains difficult to determine the optimal opening pressure of the low-pressure
      chamber of the DSV for ideal clinical improvement. Therefore a new hydrostatic
      gravitational "programmable" valve (proGAV), entitled on avoiding the
      disadvantages of other adjustable devices, has been developed and implanted in 16
      patients with promising results.

PMID- 16463857
TI  - Three-year outcome of shunted idiopathic NPH patients.
AB  - The incidence of idiopathic normal pressure hydrocephalus (iNPH) has increased as
      a result of improved longevity. This report describes the 3-year outcome of
      shunted iNPH patients compared to three-month outcome after shunting. Patients (n
      = 50) (Age 70.4 +/- 8.9) admitted to our service were diagnosed and treated
      according to a fixed protocol for management of iNPH and after shunting were
      followed at least three times per year in clinic. The outcome of 50 patients was
      graded according to the level of improvement in symptoms as Excellent/Good,
      Partial or None in each category of Gait, Incontinence and Dementia. If we lump
      favorable (excellent, good, partial recovery) vs poor recovery (none), we found
      from 3 months to 3 years, a moderate decline in gait performance (91% to 75%), a
      retention of memory improvement (80%-80%) and an improvement in incontinence
      occurred over time (70%-82.5%). With proper diagnosis and management of iNPH,
      shunting of patients is associated with a favorable risk/benefit ratio that is
      reasonably long lasting.

PMID- 16463858
TI  - Clinical testing of CSF circulation in hydrocephalus.
AB  - INTRODUCTION: Recent 'NPH Dutch trial' has re-emphasised the importance of the
      resistance to cerebrospinal fluid (CSF) outflow (Rcsf) in the diagnosis of
      hydrocephalus. We re-evaluated the clinical utility of the physiological
      measurements revealing CSF dynamics. The results were summarized from our
      previous publications. The Computerised Infusion Test was designed to perform
      quick and low-invasive assessment of CSF dynamics described by parameters as
      Rcsf, brain compliance, elasticity coefficient, estimated sagittal sinus
      pressure, CSF formation rate and other variables. Overnight ICP monitoring with
      quantitative analysis of CSF dynamics was used in those cases where infusion
      study was unreliable or producing results close to the borderline. We found that
      the threshold of normal and increased Rcsf should be age-matched because in
      patients older than 55 Rcsf increases 0.2 mm Hg/(ml/min) per year (p < 0.04: N =
      56). Rcsf was positively correlated with cerebral autoregulation (R = 0.41; p <
      0.03; N = 36) indicating that in patients with symptoms of NPH but normal Rcsf
      underlying cerebrovascular disease is more frequent. Computerized infusion tests
      and overnight ICP monitoring are useful diagnostic technique alone or in
      conjunction with other forms of physiological measurement.

PMID- 16463859
TI  - Intracranial baroreflex yielding an early cushing response in human.
AB  - The Cushing response is a pre-terminal sympatho-adrenal systemic response to very
      high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a
      reversible pressure-mediated systemic response. Infusion studies are routine
      procedures to investigate, by infusing CSF space with saline, the cerebrospinal
      fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at
      assessing systemic and cerebral haemodynamic changes during moderate rise of ICP
      in human. Infusion studies were performed in 34 patients. This is a routine test
      perform in patients presenting with symptoms of NPH during their pre-shunting
      assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV)
      were non-invasively monitored with photoplethysmography and transcranial Doppler.
      The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a
      significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP
      (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to
      51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min
      to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to
      0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study
      demonstrated that a moderate rise of ICP yields a reversible pressure-mediated
      systemic response, demonstrating an early Cushing response in human and a
      putative intracranial baroreflex.

PMID- 16463860
TI  - Does the ventricle size change after shunt operation of normal-pressure
      hydrocephalus?
AB  - OBJECTIVES: The aim of this study was to determine whether ventricular size
      correlates with a positive clinical outcome following shunt placement.
      Hydrostatic valves (Dual-Switch-Valves) were implanted in 80 patients with NPH at
      Unfallkrankenhaus Berlin between September 1997 and January 2002. One year
      postoperatively, these patients underwent computerized tomography scanning, and
      their ventricular size was ascertained using the Evans-Index. Among 80% of the
      patients who showed no postoperative change in ventricular volume, 59%
      nonetheless had good to excellent clinical improvements, 17% satisfactory
      clinical improvement, and 24% no improvement. Furthermore, a moderate reduction
      in ventricular size was observed in 14% of patients in this cohort. Among these,
      36% experienced a good to excellent clinical improvement, 28% a satisfactory
      improvement, and 36% unsatisfactory improvement. A marked reduction in
      ventricular size was observed in 6% of the patients. Of this group, 60%
      demonstrated good to excellent outcomes, whereas 40% had unsatisfactory outcomes.
      Favourable outcomes following the implantation of a hydrostatic shunt in patients
      with NPH did not correlate with decreased ventricular volume 1 year after
      surgery. In fact, better clinical outcomes were observed in patients with little
      or no alteration in ventricular size, compared with those in patients with marked
      decrease in ventricular size. A postoperative change in ventricular volume should
      be assessed differently in patients with NPH compared with those suffering from
      hypertensive hydrocephalus.

PMID- 16463862
TI  - Secondary insults and outcomes in patients with hypertensive basal ganglia
      hemorrhage.
AB  - This study was designed to monitor secondary insults and their impact on outcomes
      of patients with hypertensive basal ganglia hemorrhage (HBGH). One hundred and
      twelve patients with HBGH (male 73, female 39) of age 42 +/- 8 years (range from
      38 to 57 years) were studied. Operations included craniotomy or trephination
      drainage with urokinase thrombolysis. Conventional therapies were also given to
      the patients including the administration of mannitol, crystalloid and colloid
      solution. In the meantime, blood pressure (MAP), temperature (T) and SaO2 and
      other parameters were recorded in the intensive care unit. The ICP values were
      recorded, and the early clinical outcome was assessed upon discharge according to
      Glasgow Outcome Scale. Cerebral Perfusion Pressure was calculated as CPP = MAP
      MICP. Outcomes in the group without secondary insults were better than that in
      the group with secondary insults (P < 0.01). No unfavorable outcomes were found
      in the 59 cases managed by ultra-early surgery whereas 36.1% of the cases
      operated after 6 hours of onset had unfavorable outcomes. It is concluded that
      the high incident rate of secondary insults in HICH patients influences outcome.
      Ultra-early surgery may also contribute to improved quality of survival.

PMID- 16463861
TI  - Intravenous magnesium sulfate to improve outcome after aneurysmal subarachnoid
      hemorrhage: interim report from a pilot study.
AB  - OBJECTIVES: Magnesium sulfate (MgSO4) may be useful in preventing neurological
      injury after subarachnoid haemorrhage (SAH). In this randomized, double-blind
      study we evaluated the safety and efficacy of MgSO4 infusion to improve clinical
      outcome after aneurysmal SAH. METHODS: With ethics committee approval and
      informed consents, 45 patients with SAH were randomly allocated to receive either
      MgSO4 80 mmol/day or saline infusion for 14 days. All patients also received
      intravenous nimodipine. Episodes of vasospasm were treated with hypertensive,
      hypervolemic therapy. Neurological status was assessed 3 months after haemorrhage
      using Barthel index and Glasgow outcome scale (GOS). Incidences of cardiac and
      pulmonary complications were also recorded. Data were compared between groups
      using Mann-Whitney or Fisher exact tests as appropriate. P < 0.05 was considered
      significant. RESULTS: Patient characteristics, severity of SAH and surgical
      treatment did not differ between groups. Although the number of episodes was not
      reduced, MgSO4 shortened the duration of vasospasm. Patients receiving MgSO4
      tended to have fewer neurological deficits, better functional recovery and an
      improved score in GOS. However, none of these outcome variables reached
      statistical significance. The incidence of cardiac and pulmonary complications in
      the MgSO4 group (43%) was also similar to that in the saline group (59%), P =
      0.14. CONCLUSIONS: MgSO4 infusion after aneurysmal SAH is well tolerated and may
      be useful in producing better outcome. A larger study is required to confirm the
      neuroprotective effect of MgSO4.

PMID- 16463863
TI  - Balance of risk of therapeutic hypothermia.
AB  - The complications of therapeutic hypothermia sometimes undermine its clinical
      effects. In this study we investigated the efficacy and safety of therapeutic
      hypothermia based on analysis of 20 severe head injury cases from 6 institutions
      treated with therapeutic hypothermia in 1999. The twenty patients with severe
      head injury were enrolled prospectively based on the following indications;
      Glasgow Coma Scale of 7 or less on admission, age 60 or younger, and systric BP
      over 100 mmHg. A control group consisting of 21 patients with severe head injury
      met the same criteria but were treated without therapeutic hypothermia in other
      institutions. Clinical benefit were evaluated by a comparison of clinical result
      in the two groups defined according to the Glasgow Outcome Scale six months after
      injury. The hypothermia group was divided into two groups based on a target
      temperature [mild hypothermia group: 32-34 degrees C (n = 10); very mild
      hypothermia group: 35-36 degrees C (n = 10)]. The complication rate, clinical
      results and the duration of therapeutic hypothermia were analyzed between two
      groups. In the hypothermia group, 12 patients obtained a favorable outcome (Good
      Recovery or Moderate Disabled in GOS) and the mortality rate was 35%. In the
      control group, however only 5 patients had a favorable outcome and the mortality
      rate was 57%. Comparison between mild hypothermia and very mild hypothermia
      groups revealed no difference in clinical outcome. In the hypothermia group,
      severe pneumonia was seen in three patients, all in the mild hypothermia group
      with a hypothermic duration of over 120 hours. Mild hypothermia should be ended
      within 120 hours to avoid severe complication. When long-lasting therapeutic
      hypothermia of more than 120 hours is planned, very mild hypothermia is the
      treatment of choice.

PMID- 16463864
TI  - The influence of mild hypothermia on ICP, CPP and outcome in patients with
      primary and secondary brain injury.
AB  - Aim of this study was to examine the hypothesis that only a subgroup of patients
      with lesser primary brain damage after severe head injury may benefit from
      therapeutic hypothermia. We prospectively analysed 72 patients with severe head
      injury, randomized into groups with (n = 37) and without (n = 35) hypothermia of
      34 degrees C maintained for 72 hours. The influence of hypothermia on ICP, CPP
      and neurological outcome was analysed in the context of the extent of primary
      brain damage. Patients with normothermia and primary lesions (n = 17) values: GCS
      on admission 5 (median), ICP 18.9 (mean), CPP 73 (mean), GOS 4 (median). Patients
      with normothermia and extracerebral hematomas (n = 20): GCS 4, ICP 16, CPP 71,
      GOS 3. Patients with hypothermia and primary lesions (n = 21): GCS 4,62, ICP 10,
      81, CPP 78,1, GOS 4. Patients with hypothermia and extracerebral hematomas (n =
      14): GCS 5, ICP 13.2, CPP 78, GOS 5. Hypothermia decreased ICP and increased CPP
      regardless of the type of brain injury. Hypothermia was not able to improve
      outcome in patients with primary brain lesions but this pilot study suggests that
      it significantly improves outcome in patients with extracerebral hematomas.

PMID- 16463865
TI  - Contribution of raised ICP and hypotension to CPP reduction in severe brain
      injury: correlation to outcome.
AB  - The aim of this study was to determine to what degree hypotension and ICP
      contribute to the reduction of cerebral perfusion pressure (CPP), particularly in
      light of the shift in emphasis to CPP management by the use of pressors. The
      study population consisted of severely head injured patients extracted
      retrospectively from the Traumatic Coma Data Bank and compared with 139 patients
      from the Smith Kline component of the American Brain Injury Consortium database
      where outcome was available. The percentage time that ICP exceeded 20 mm Hg and
      CPP less than 60 mm Hg was computed for 5 days post injury. At each hour when CPP
      was less than 60 mm Hg the contribution of raised ICP and low arterial pressure
      or both was determined. In the first cohort, hypotension was the predominant
      factor leading to CPP reduction. With use of the CPP concept of treatment, the
      major contribution to CPP shifted to ICP and arterial hypotension played less of
      a role. Overall, CPP management has been associated with improved outcome.

PMID- 16463866
TI  - Mortality from traumatic brain injury.
AB  - It is the general sense that mortality has been decreasing in recent years
      compared to earlier studies described by the NIH traumatic coma data bank. We
      studied mortality during the period of 1984 to 1996 to determine if indeed
      mortality from severe traumatic brain injury was decreasing and to identify
      factors which might account for the reduction. The study population (N = 1839)
      consisted of severely head injured patients extracted retrospectively from the
      TCDB (635), MCV (382), and 822 patients from clinical trial databases conducted
      in the United States. Mortality was obtained from each of the databases for the
      age range form 16 to 65. Penetrating injury and treatment groups in the clinical
      trial databases were excluded. Mortality in the year 1984 equaled 39% and
      gradually decreased to a level of 27% in 1996. When adjusting for age, motor
      score and pupil reaction, the mortality of the period from 1984 to 1987 was
      significantly higher (p < 0.05) than that of the period 1988 to 1996. During the
      period 1984 through 1996, mortality from severe brain injury steadily declined.
      Factors other than age, motor score and pupil reactivity over time are
      responsible for this reduction. This reduction over time is an important factor
      for prognostic modeling of TBI.

PMID- 16463867
TI  - Assessment of different data representations and averaging methods on the
      Spiegelberg compliance device.
AB  - The Spiegelberg Compliance Device (Spiegelberg KG, Hamburg, Germany) has been
      available for the automated measurement and calculation of minute by minute
      intracranial compliance. Widespread practical use has been somewhat limited by
      the instability of values: especially at low intracranial pressures. We looked at
      two aspects of a methodology in an attempt to increase the value of the
      Spiegelberg device in the clinical setting. Firstly, we discussed the difference
      in representing measured values as elastance (dp/dv) instead of compliance
      (dv/dp); and secondly we proposed the use of an averaging algorithm called the
      Exponentially Weighted Moving Average (ewma), which could be applied as a
      flexible method to follow trends and rapid changes in the elastance (or
      compliance). Clinical data from sixteen patients were gathered and statistical
      analysis was focused on three particular aspects, the coefficient of variation
      which indicates the variability of data values, the correlation between the
      elastance (or compliance) time series and the underlying ICP signal and the
      percentage of outliers greater than 2.5 standard deviations from the mean. Our
      results showed that expressing elastance (dp/dv) instead of compliance (dv/dp)
      yielded fewer outliers and had a better correlation to ICP, and the ewma method
      had a better correlation to ICP than the Spiegelberg method.

PMID- 16463868
TI  - Assessment of the relationship between age and continuous intracranial
      compliance.
AB  - The aim of this open, descriptive and prospective study was to determine if the
      new monitoring parameter "continuous intracranial compliance (cICC)" decreases
      with age in patients with traumatic brain injury (TBI). 30 patients with severe
      and moderate TBI (Glasgow Coma Scale score < or = 10) contributing to a European
      multicenter study, organized by the Brain-IT group, underwent computerized
      monitoring of blood pressure, intracranial pressure (ICP), cerebral perfusion
      pressure and cICC. Regression analyses of individual median ICP and median cICC
      versus patients' age revealed no significant dependency. Median cICC declined
      significantly with increasing ICP (when median ICP = 10, 20 and 30 mmHg, cICC =
      0.64, 0.56 and 0.42 ml/mmHg respectively, p < 0.05). These three ICP groups were
      then subdivided according to age (0-20, 21-40, 41-60 and 61-80 years). Median
      cICC declined with age in both high ICP groups (median ICP = 20,30 mmHg).
      Percentage cICC values below a set pathological threshold of lower than 0.05
      ml/mmHg across the four age groups were 28% (0-20 yrs), 59% (21-40 yrs), 60% (41
      60 yrs) and 70% (61-80 yrs) respectively. The observed phenomenon of decreased
      intracranial volume challenge compensation with advancing age may contribute to
      the well-known fact of a worse outcome in elderly patients after TBI.

PMID- 16463870
TI  - Non-invasive measurement of intracranial compliance using cine MRI in normal
      pressure hydrocephalus.
AB  - The aim of this study is to clarify biophysics of normal pressure hydrocephalus
      (NPH) based on non-invasive intracranial compliance measurement using magnetic
      resonance imaging (MRI). Patients with NPH after subarachnoid hemorrhage (NPH
      group, n = 5), brain atrophy or asymptomatic ventricular dilation (VD group, n =
      5), and healthy volunteers (control group, n = 12) were included in this study.
      Net blood flow (bilateral internal carotid and vertebral arteries, and jugular
      veins) and cerebrospinal fluid (CSF) flow in subarachnoid space at the C2 level
      of cervical vertebra were measured using phase-contrast cine MRI. CSF pressure
      gradient and intracranial volume changes during a cardiac cycle were calculated
      based on Alperin's method. Compliance index (Ci = delta V/delta P) was obtained
      from the maximum pressure gradient and volume changes. Pressure volume response
      (PVR) was measured in the NPH group during a shunt operation. Ci in the NPH group
      was the lowest among the three studies groups. No difference was found between
      the control and VD groups. There was a linear correlation between Ci and PVR. In
      conclusion, intracranial compliance can be determined by cine MRI non-invasively.
      It is well known that NPH has relatively low intracranial compliance, this non
      invasive method can be used for the diagnosis of NPH.

PMID- 16463869
TI  - Cerebral haemodynamic assessment in patients with thalamic haemorrhage: a pilot
      study with continuous compliance monitoring.
AB  - OBJECTIVE: Thalamic brain haemorrhage is a common disabling and potentially fatal
      condition. However, management is mainly supportive, very rarely do neurosurgeons
      resort to evacuation of the haematoma. We hypothesised that cerebral haemodynamic
      abnormalities in the forms of lost pressure autoregulatory response (PAR) and/or
      impaired cerebral vasoreactivity (CVR) to carbon dioxide may indicate the
      haematoma should be aspirated to prevent further brain damage. MATERIAL AND
      METHODS: Patients with thalamic haemorrhage were selected on clinical ground for
      intracranial pressure (ICP) monitoring and intensive care management. Spiegelberg
      double lumen intraventricular balloon catheter was inserted as any other fluid
      filled ICP monitoring technique, on the side of the haematoma. Data of ICP,
      arterial blood pressure (ABP), cerebral perfusion pressure (CPP) and intracranial
      compliance were collected on a minute basis. Hourly averages were used for
      analysis. To assess PAR and CVR, blood flow velocity (BFV) in both middle
      cerebral arteries were measured continuously by transcranial Doppler (TCD)
      ultrasonography. RESULTS: Six patients with medium (15-25 ml) to large (>25 ml)
      haematoma volume were subjected to ultrasoud-guided aspiration. 51 CVR and 53 PAR
      tests were performed. 80820 sets of data were prospectively collected.
      Progressive reduction in ICP and sustained improvement in compliance and BFV were
      observed after aspiration. Impairment in PAR and/or CVR was consistent with
      clinical deterioration in four patients. Such disturbance was normalised after
      aspiration. Increments in BFV and improvement in compliance were demonstrated.
      CONCLUSIONS: Cerebral haemodynamic abnormalities in thalamic haematomas can be
      demonstrated by the non-invasive TCD ultrasonograpy. These abnormalities can be
      corrected by aspiration of the haematoma, and hence improve intracranial
      compliance.

PMID- 16463871
TI  - Pulse and mean intracranial pressure analysis in pediatric traumatic brain
      injury.
AB  - OBJECTIVE: We investigated the relationship between the intracranial pulse
      pressure (ICPpp) and the mean intracranial pressure (ICP(M)) in pediatric
      patients with traumatic brain injury (TBI). METHODS: We screened ICP records of
      42 patients admitted to the Pediatric Intensive Care Unit at Doernbecher
      Children's Hospital (OHSU) for segments in which the ICPM varied at least 5 mmHg.
      We found 54 ICP segments in 9 pediatric TBI patients (ages 0.2-17.8 years, mean =
      9.9). ICP was continuously monitored (fs = 125 Hz). We used an automatic
      algorithm to detect ICP beat components. We then calculated the ICPpp and ICPM
      for each beat and created density plots of ICPpp vs. ICPM. RESULTS: The
      coefficient of linear correlation was r > 0.70 in 43/54 segments (p < 0.01). We
      found that an underlying linear relationship exits between ICPpp and ICPM in most
      1-hour records of pediatric patients with TBI. This finding is consistent with
      the data in adult studies, suggesting that children with TBI demonstrate similar
      changes in brain compliance. However, density plots revealed that there are also
      nonlinear ICPpp-ICPM patterns present that are not captured by linear metrics.
      CONCLUSION: Although there is an underlying linear relationship between ICPpp and
      ICPM, nonlinear patterns are also present. Further research is required to
      determine if specific nonlinear ICPpp-ICPM patterns correlate with clinically
      significant information.

PMID- 16463872
TI  - Preliminary report on spiegelberg pre and post-operative monitoring of severe
      head-injured patients who received decompressive craniectomy.
AB  - The monitoring of craniospinal compliance is uncommonly used clinically despite
      it's value. The Spiegelberg compliance monitor calculates intracranial compliance
      (C = deltaV/deltaP) from a moving average of small ICP perturbations (deltaP)
      resulting from a sequence of up to 200 pulses of added volume (deltaV = 0.1 ml,
      total V = 0.2 ml) made into a double lumen intraventricular balloon catheter. The
      objective of this study was thus to determine the effectiveness of the
      decompressive craniectomy done on the worst brain site with regard to compliance
      (Cl), pressure volume index (PVI), jugular oximetry (SjVo2), autoregulation
      abnormalties, brain tissue oxygen (TiO2) and cerebral blood flow (CBF). This is a
      prospective cohort study of 17 patients who were enrolled after consent and
      approval of the ethics committee between the beginning of the year 2001 and end
      of the year 2002. For pre and post assessment on compliance and PVI, all 12
      patients who survived were reported to become normal after decompressive
      craniectomy. There is no significant association between pre and post craniectomy
      assessment in jugular oxymetry (p > 0.05), autoregulation (p > 0.05),
      intracranial brain oxymetry (p = 0.125) and cerebral blood flow (p = 0.375).
      Compliance and PVI improved dramatically in all alive patients who received
      decompressive craniectomy. Compliance and PVI monitoring may be crucial in
      improving the outcome of severe head injured patients after decompressive
      craniectomy.

PMID- 16463873
TI  - Age-dependence of cerebrospinal parameters.
AB  - OBJECTIVE: The records of 159 patients were reviewed who routinely underwent a
      classical volume-pressure testing procedure due to suspected cerebrospinal fluid
      circulatory disorders. METHODS: Regression analyses were carried out to explain
      the cerebrospinal parameters' relationships to age. Least median squares (LMS)
      algorithms achieved robust estimation of simple linear model parameters. Also,
      method of weighted regression was used because of unequal variances in the
      observations. RESULTS: Cerebrospinal elastance and resistance to outflow revealed
      significant LMS regressions: y = 0.171x + 7.460 (n = 159, p < 0.0001) and y =
      0.096x + 1.871 (n = 97, p < 0.0001), respectively. Similarly, weighting data
      resulted in models such as y = 0.151x + 6.830 (p < 0.0001) for elastance and y =
      0.087x + 1.730 (p < 0.0001) for resistance estimates. The intracranial pressure
      at rest showed no age-related dependency. Both clear clinical and morphological
      signs were found in 20% of patients. CONCLUSION: Expecting no time-variant
      properties we surprisingly found a significant linear relationship in
      cerebrospinal parameters and age. Thus, parameter magnitudes are not likely
      dominated by a pathological process only but also determined by temporal system
      alterations.

PMID- 16463874
TI  - A computer model of intracranial pressure dynamics during traumatic brain injury
      that explicitly models fluid flows and volumes.
AB  - A model of intracranial pressure (ICP) dynamics that uses fluid volumes as
      primary state variables is presented, along with clinical data for two subjects
      with elevated ICP. The data includes annotations to indicate the precise timing
      of clinical changes in cerebral spinal fluid drainage, head of bed elevation, and
      minute ventilation. The response to changes in the clinical parameters was used
      to calibrate the model to correspond to specific subjects by estimating values
      for key characteristics such as hematoma volume and CSF uptake resistance. The
      error in mean ICP predicted by the model was less than 2 mmHg when cerebral
      spinal fluid is drained and the head of bed elevation was increased. The error in
      mean ICP predicted by the model exceeded 5 mmHg during an episode when the head
      of bed was decreased and also during a reduction in minute ventilation. The
      estimated values for hematoma volume and other subject characteristics were
      plausible but could not be verified empirically.

PMID- 16463875
TI  - Plateau waves: changes of cerebrovascular pressure transmission.
AB  - OBJECTIVE: To test the validity of the hypothesis that active vasodilatation and
      vasoconstriction underlie the occurrence of intracranial pressure (ICP) plateau
      waves by evaluating corresponding changes of cerebrovascular pressure
      transmission of arterial blood pressure (ABP) to ICP. METHODS: Digitized
      recordings of ICP and ABP sampled at 30 Hz were obtained from nine patients with
      traumatic brain injury. For each 16.5 s recording interval mean values of ICP,
      ABP, cerebral perfusion pressure (CPP), and the corresponding highest modal
      frequency (HMF) of cerebrovascular pressure transmission were calculated.
      RESULTS: Mean ICP and HMF significantly increased (P < 0.003) and mean CPP
      decreased significantly (P < 0.00036) at onset of the wave. Conversely at
      termination, mean ICP and HMF significantly decreased (P < 0.026) and mean CPP
      significantly increased (P < 0.028). In addition, the strong negative
      correlations between mean ICP and mean CPP (r = -0.87) and mean HMF and CPP (r = 
      0.87) were demonstrated. CONCLUSION: The findings that HMF increased at onset and
      decreased at the termination of plateau wave support the validity of the
      vasodilatatory/constriction cascade model that postulates active vasodilation at
      the onset and active vasoconstriction of the cerebrovascular bed at the
      termination of a plateau wave.

PMID- 16463876
TI  - Brain tissue biomechanics in cortical contusion injury: a finite element
      analysis.
AB  - The controlled cortical impact model has been used extensively to study focal
      traumatic brain injury. Although the impact variables can be well defined, little
      is known about the biomechanical trauma as delivered to different brain regions.
      This knowledge however could be valuable for interpretation of experiment
      (immunohistochemistry etc.), especially regarding the comparison of the regional
      biomechanical severity level to the regional magnitude of the trauma sequel under
      investigation. We used finite element (FE) analysis, based on high resolution T2
      weighted MRI images of rat brain, to simulate displacement, mean stress, and
      shear stress of brain during impact. Young's Modulus E, to describe tissue
      elasticity, was assigned to each FE in three scenarios: in a constant fashion (E
      = 50 kPa), or according to the MRI intensity in a linear (E = [10, 100] kPa) and
      inverse-linear fashion (E = [100, 10] kPa). Simulated tissue displacement did not
      vary between the 3 scenarios, however mean stress and shear stress were largely
      different. The linear scenario showed the most likely distribution of stresses.
      In summary, FE analysis seems to be a suitable tool for biomechanical simulation,
      however, to be closest to reality tissue elasticity needs to be determined with a
      more specific approach, e.g. by means of MRI elastography.

PMID- 16463877
TI  - Modifications of spontaneous cerebral blood flow oscillations during
      cardiopulmonary bypass.
AB  - Spontaneous slow waves are present in the systemic circulation including the
      intracranial compartment. They are supposed to reflect the cerebral
      autoregulation. We hypothesised that in the absence of cardio respiratory
      variability, during cardiopulmonary bypass (CPB), we should reveal extreme
      physiologic controls. MATERIAL/METHODS: Ten patients were included. Arterial
      blood pressure (ABP, radial invasive), extracorporeal circuitry pressure and
      cerebral blood flow velocity (CBFV, middle cerebral artery) were recorded. We
      analysed the slow waves in the B (8 to 50) and the UB (>50 to 200) bands (in
      milli-Hz). The analysis, before and during CPB, was performed in the tine domain
      (correlation coefficient, entropy, mean quantity of mutual information, relative
      entropy) and in the frequency domain (spectrogram, frequency spectrum,
      coherence). RESULTS: CPB dramatically changed monitored signals decreasing their
      entropy and revealing a dominant CBFV 70 mHz-frequency and a dominant ABP 9 mHz
      frequency. There was no association between the signals (p < 0.05). Before CPB we
      found complex patterns where B and UB waves were present. CONCLUSION: We
      hypothesised that CPB provoked a highly protective mechanism, reducing the
      fluctuations of CBF, by a deactivation of B waves, revealing monotonous UB waves.

PMID- 16463878
TI  - Concept of "true ICP" in monitoring and prognostication in head trauma.
AB  - OBJECTIVE: To propose a new coefficient, which contains information about both
      the absolute ICP and the position of the 'working point' on the pressure-volume
      curve. METHOD: ICP was monitored continuously in 187 sedated and ventilated
      patients. The RAP coefficient was calculated as the running (3 minutes)
      correlation coefficient between slow changes in pulse amplitude and mean ICP. RAP
      has value 0 on the flat part of the Pressure-Volume Curve and +1 on the ascending
      exponential part. Then RAP decreases to zero or becomes negative when ICP
      increases further and affects cerebrovascular pressure-reactivity (which flattens
      the pressure-volume curve). Variable tICP = ICP* (1 - RAP) has been called
      'trueICP'. It magnifies the critical values of ICP when cerebrovascular
      reactivity is exhausted and dampens those states where absolute ICP is elevated
      but vascular reactivity is not affected. RESULTS: Both Mean ICP and RAP were
      independently correlated with outcome (ANOVA:ICP-GOS: F = 22; p < 0.00001, RAP
      GOS: F = 9; p < 0.001). 'TrueICP' had stronger association with outcome: F = 28;
      p < 0.000001. Mortality in those patients having 'trueICP' above the threshold of
      19 mm Hg was above 80%, while the mortality in those having cICP below 19 mm Hg
      was only 20% (F = 80; p < 10(-8)). 'TrueICP' was also suitable for continuous
      monitoring: sustained rise in tICP above 19 mm Hg was strongly associated with
      fatal complications. CONCLUSION: The proposed variable is a powerful predictor of
      fatal outcome following head injury. It is sensitive to both the rising absolute
      ICP and the critical loss of cerebrovascular regulation.

PMID- 16463879
TI  - Fuzzy pattern classification of hemodynamic data can be used to determine
      noninvasive intracranial pressure.
AB  - OBJECTIVE: The authors previously introduced a method in which intracranial
      pressure (ICP) was estimated using parameters (TCD characteristics) derived from
      cerebral blood flow velocity (FV) and arterial blood pressure (ABP). Some results
      suggested that this model might be influenced by the patient's state of cerebral
      autoregulation and other clinical parameters. Hence, it was the aim of the
      present study to improve the method by modifying the previously used global
      procedure in certain subgroups of patients. METHODS: In 103 traumatic brain
      injured patients (3-76 years, mean: 31 +/- 16 years) signal data of FV, ABP and
      ICP were used to generate samples of TCD characteristics together with time
      corresponding ICP. Fuzzy Pattern Classification was used to identify cluster
      subsets (classes) of the sample space. On each class a local estimator of ICP was
      defined. This approach provides a non-invasive assessment of ICP (nICP) as
      follows: Using FV and ABP the TCD characteristics were computed and related to
      the matching classes. nICP was calculated as a weighted sum of local ICP
      estimations. RESULTS: ICP A and B waves and long-term trends could be visibly
      assessed. The median absolute difference between ICP and nICP was 5.7 mmHg.
      CONCLUSIONS: The class structure of the model facilitates nICP assessment in
      heterogeneous patient groups and supports a stepwise extension of the target
      patient group without affecting the former validity.

PMID- 16463880
TI  - Clinical experience with the noninvasive ICP monitoring system.
AB  - The Noninvasive ICP (Intracranial Pressure) Monitoring System NIP-200/210 has
      been used in several hospitals with more than 2000 patients since March 2002. It
      is based on the N2 wave response to flash visual evoked potentials (FVEP).
      According to our data, the mean latency period for the FVEP-induced N2 wave in
      healthy controls was 126.61 +/- 14.64 ms, in which that of females was shorter
      than that of males (123.95 +/- 10.345 ms vs. 130.75 +/- 14.632 ms; p < 0.05).
      There was no significant difference between the left or right side response
      (126.71 +/- 14.91 ms vs. 124.468 +/- 15.043 ms, p > 0.05). No significant
      difference in latency was found across age groups in our patient pool. In
      general, the N2 wave was stable and easily identified in most of the patients or
      healthy controls. When the data obtained with the NIP-200/210 Noninvasive ICP
      Monitoring System was compared with that from invasive techniques, the results
      were quite consistent (correlation index 0.651-0.97, standard error 8-15%). From
      our clinical trial results, we conclude that the latency periods for the FVEP
      induced N2 wave reflected ICP values. However this technique is not suitable in
      patients with bifrontal hematoma, retinal concussion, or contusion of the optical
      nerve, because an FVEP value cannot be measured accurately in these cases. In our
      clinical trials, we used the FVEP technique to determine the effectiveness of
      mannitol in decreasing the ICP. The data revealed that ICP values decreased
      significantly within 20 minutes after a mannitol injection, and reached a minimum
      level at 40 minutes. For a single bolus of mannitol, the duration of the ICP
      decrease ranged from 30-210 minutes. Elevated ICP is one of the most important
      clinical issues in neurosurgery and neurology. The present noninvasive technique
      is safe and easy to perform, with a minimal risk of complications.

PMID- 16463881
TI  - Innovative non-invasive method for absolute intracranial pressure measurement
      without calibration.
AB  - A new absolute ICP (aICP) measurement method was designed which does not need
      calibration. In this study we compared a new method with invasive aICP method in
      ICU on the patients with closed severe traumatic brain injury. A new method is
      based on two-depth TCD technique for aICP and external absolute pressure aPe
      comparison using the eye artery (EA) as natural "balance". The intracranial
      segment of EA is compressed by aICP and the extracranial segment is compressed by
      aPe applied to the tissues surrounding the eye. The blood flow parameters in both
      EA segments are approximately the same when aPe = aICP. Two-depth TCD device is
      used as an indicator of balance aPe = aICP when the pulsatility index of blood
      flow velocity waveform in intracranial and extracranial segments are the same.
      Fifty seven simultaneous invasive and non-invasive aICP measurements were
      performed in aICP range from 3.0 to 37.0 mmHg. Bland Altman plot of the
      differences between simultaneous invasive and non-invasive aICP measurements
      shows the negligible mean difference (mean = 0.94 mmHg) with a standard deviation
      of 6.18 mmHg. This validation study shows that it is possible to measure aICP non
      invasively without calibration of the system with 95% confidence interval of 12
      mmHg.

PMID- 16463882
TI  - The correlation of midline shifts of human brain with large brain haematoma using
      a finite element approach.
AB  - OBJECTIVES: We report on using a computational (finite element) model to simulate
      a human skull-brain structure to quantify the distortion of brain. METHODS: We
      simulated various effects of brain haematoma causing the distortion of brain.
      Midline shifts of the human brain in relation to size and location of haematoma
      were compared with the theoretical prediction. RESULTS: Prediction of midline
      shifts in lobar space-occupying lesions was more accurate that in deep-seated
      ones (such as thalamic lesions). DISCUSSION: More accurate boundary conditions of
      space-occupying lesions and better knowledge of physical materials properties of
      brain tissues can improve predictions of brain deformation using mathematical
      models.

PMID- 16463884
TI  - Increased intracranial pressure induces a rapid systemic interleukin-10 release
      through activation of the sympathetic nervous system.
AB  - There is a bi-directional communication between the immune and central nervous
      system. In this context, it is known that patients with traumatic brain injury
      suffered from systemic immunodepression and an increased risk to develop
      infectious complications. We investigated the role of an increased intracranial
      pressure (ICP) and sympathetic activation on systemic immune changes. A sustained
      increase in ICP was achieved by inflation of a subdural balloon. At different
      time points, plasma levels of the anti-inflammatory cytokine, interleukin (IL)
      10, were measured. Furthermore, the effect of a sympathetic blockade by co
      administration of the beta2-adreoreceptor antagonist, propranolol, was evaluated.
      Finally, we examined the impact of epinephrine infusion on blood IL-10 levels. We
      showed that an increase in ICP with activation of the sympathetic nervous system
      was able to induce systemic release of IL-10. This effect was blocked by
      administration of the beta2-adreoreceptor antagonist. Furthermore, epinephrine
      infusion directly induced systemic release of IL-10. Our data suggested that
      sympathetic activation with release of epinephrine may induce systemic
      immunodepression with risk of infectious complications in brain-injured patients.

PMID- 16463883
TI  - Clinical study of continuous non-invasive cerebrovascular autoregulation
      monitoring in neurosurgical ICU.
AB  - Ultrasonic "time-of-flight" monitor (Vittamed) was used for continuous monitoring
      of intracranial blood volume (IBV) pulse, respiratory, slow waves and
      cerebrovascular autoregulation (CA). The objectives are to compare of invasively
      and non-invasively monitored slow intracranial waves and CA of ICU patients and
      to evaluate the phase shift between ABP and IBV respiratory waves as a possible
      estimator of CA. CA monitoring has been performed in 13 patients with severe TBI
      (age mean/range 30.5/(18-64)). Data were collected from 87 one-hour sessions of
      simultaneous invasive and non-invasive wave monitoring and from 53 one-hour
      sessions of invasive and non-invasive CA monitoring. High correlation (R > 0.9)
      has been obtained between invasively and non-invasively recorded intracranial
      slow waves. Bland Altman difference between invasively and non-invasively
      recorded intracranial slow waves is clinically not significant (mean =-0.07, SD =
      0.089, alpha = 0.05). Agreement has been confirmed between invasive and non
      invasive CA monitoring data in a wide range of R = [-0.85; +0.96]. Hypothesis of
      the coincidence of invasive and non-invasive CA assessment is accepted (p <
      0.05). Phase shift monitoring of permanent respiratory ABP waves and IBV waves
      permit continuous non-invasive CA estimation without unnatural physical or
      pharmacological stimulations of CA system.

PMID- 16463885
TI  - Experimental model for investigating hyponatremia after subarachnoid hemorrhage
      in rats.
AB  - Hyponatremia is a common complication in patients with aneurysmal subarachnoid
      hemorrhage (SAH). Such patient demonstrates excessive natriuresis and an
      increased risk of symptomatic cerebral vasospasm. However, the precise mechanisms
      underlying SAH induced hyponatremia remain unclear. In the present study, in
      order to establish an experimental model of hyponatremia following SAH, we
      induced SAH in rats, and evaluated the serum sodium (Na) levels, Na excretion and
      physiological parameters. Twenty-four male Wistar rats were used. SAH was induced
      by an endovascular puncture method. The mean arterial pressure (MAP),
      intracranial pressure (ICP), and cerebral blood flow (CBF) were monitored
      continuously. The urine was collected cumulatively for 12 hours after SAH, and
      the urine Na concentration was determined with a spectrophotometer. The serum Na
      levels were measured at 12 hrs, 2 and 4 days following the SAH induction. The
      mean (+/- standard deviation) baseline ICP was 3.5 +/- 2.6 mmHg, and increased to
      67.4 +/- 17.6 mmHg immediately following induction of SAH. CBF decreased rapidly,
      and then gradually recovered to 70-80% of baseline. The urine volume and total Na
      excretion were significantly increased in comparison to those of the sham (P <
      0.05). The serum Na level was significantly decreased at 4 days following SAH (P
      < 0.05). The present results demonstrated for the first time that rats with SAH
      exhibited excessive natriuresis. The endovascular puncture model is suitable for
      investigating hyponatremia that occurs concomitantly with natriuresis and
      diuresis after SAH.

PMID- 16463886
TI  - Effects of venom defibrase on brain edema after intracerebral hemorrhage in rats.
AB  - We evaluated the effects of defibrase DF-521 batroxobin on reducing brain edema
      formation and the expression of ICAM-1, complement C3d and C9 in the
      perihematomal area after intracerebral hemorrhage (ICH) in rats. A rat ICH model,
      involving infusion of autologous blood into the right basal ganglia, were used in
      this study. The animals were sacrificed at 24 and 72 hours after ICH to determine
      the water content of the brain tissue with wet/dry weight measurement. While the
      expression of ICAM-1 and complement C3d was detected using immuno-histochemistry,
      and C9 was detected semi-quantitatively with Western blot analysis in the
      perihematomal area. Perihematomal brain edema was reduced after intraperitoneally
      injection of DF-521 batroxobin 24 and 72 hours after intracerebral hemorrhage.
      Immunohistochemistry showed that there were less ICAM-I positive cells were found
      around the hematoma after intraperitoneally injection of DF-521 batroxobin 24 and
      72 hours after ICH. Immuno-histochemistry also showed that C3d deposition reduced
      significantly, and the Western blot analysis also showed the content of C9
      protein declined around the hematoma in DF-521 batroxobin treatment group at 72
      hours after ICH. Defibrase DF-521 batroxobin down-regulate ICAM-1 and complement
      C3d and C9 expression in the perihematomal area, and attenuate brain edema
      formation in ICH rats.

PMID- 16463887
TI  - Complement inhibition attenuates brain edema and neurological deficits induced by
      thrombin.
AB  - The present study examined whether thrombin activates the complement cascade in
      the brain and whether N-acetylheparin, an inhibitor of complement activation,
      attenuates brain injury induced by thrombin. There were three sets of studies. In
      the first set, rats had an intracerebral infusion of either five-unit thrombin or
      a needle insertion. Brains were sampled at 24 hours for Western blot analysis and
      immuno-histochemistry. In the second set, rats received either five-unit
      thrombin+saline, five-unit thrombin+25 microg N-acetylheparin or five-unit
      thrombin+100 microg N-acetylheparin infusion. Brains were sampled 24 hours later
      for water content measurement. In the third set, rats received either five-unit
      thrombin+saline or five-unit thrombin+ 100 microg N-acetylheparin. Behavioral
      tests sensitive to unilateral striatal damage were carried out for two weeks.
      Western blotting demonstrated that complement C9 and clusterin levels increase 24
      hours after thrombin infusion (P < 0.01). Both C9 and clusterin positive cells
      were found around the injection site. High-dose (100-microg) but not low-dose (25
      microg) N-acetylheparin attenuated thrombin-induced brain edema (81.5 +/- 0.4%
      vs. 83.7 +/- 0.3% in the vehicle, P < 0.05). Behavior was also significantly
      improved by N-acetylheparin (P < 0.05). In conclusion, thrombin-induced edema
      formation and neurological deficits were both reduced by N-acetylheparin. This
      suggests that inhibition may be a novel treatment for the thrombin-induced brain
      injury that occurs in intracerebral hemorrhage.

PMID- 16463888
TI  - Reduction of neural and vascular damage by transplantation of VEGF-secreting
      neural stem cells after cerebral ischemia.
AB  - We determined the role of VEGF-transfected neural stem cells (NSCs)
      transplantation in rat brain subjected to ischemia. Fetal NSCs were cultured from
      E14 days SD rats and transfected with VEGF121 gene by using lipofectamine
      technique. Temporary middle cerebral artery occlusion (tMCAO) models were
      established and randomly divided into 1: control group, 2: PBS transplantation
      group, 3: NSCs transplantation group and 4: VEGF-secreting NSCs transplantation
      group. Grafts were transplanted into the penumbra zones 3 days after tMCAO model
      established. Neurological Severity Score (NSS) was checked in all groups 2-12
      weeks after transplantation. By using immunofluorescent staining, VEGF expression
      of transplanted cells, differentiation and migration of transplanted NSCs after
      transplantation were detected. VEGF gene-transfected neural stem cells expressed
      gene products during the first 2 weeks. NSS in this group was significantly lower
      compared with that in other 3 groups 12 weeks after transplantation. VEGF gene
      transfected NSCs migrated and expressed VEGF in hosts' brains, some of them
      differentiated to neurons 12 weeks after transplantation. VEGF-transfected NSCs
      expressed gene products during the early time after transplantation, which reduce
      brain injury through protecting the vascular system against ischemic attack.

PMID- 16463889
TI  - Ischemia-induced endothelial cell dysfunction.
AB  - Hemorrhagic transformation upon reperfusion therapy has focused attention on
      ischemia-induced endothelial dysfunction. This study examined whether
      hyperglycemia may induce hemorrhagic transformation by enhancing endothelial
      mitochondrial damage during ischemia and whether preconditioning (PC) stimuli may
      limit ischemia-induced endothelial damage. In vivo, rats received 2.8 M D-glucose
      or arabinose (1 ml/100 g; i.p.) prior to undergoing two hours of middle cerebral
      artery occlusion and transcardiac fixation for electron microscopy. In vitro,
      brain endothelial cells were exposed to a PC impulse (short-term oxygen glucose
      deprivation; OGD) prior to an injurious event (5 hours OGD). Endothelial injury
      was assessed by measuring lactate dehydrogenase release. Hyperglycemia during
      cerebral ischemia resulted in marked changes in endothelial morphology and
      mitochondrial swelling. Thus, in the ischemic hemisphere, there was no evidence
      of endothelial mitochondrial swelling in normoglycemic rats (mean profile width
      0.22 +/- 0.04 vs. 0.17 +/- 0.01 microm in contralateral hemisphere) but there was
      marked swelling in hyperglycemic rats (0.44 +/- 0.02 microm). In vitro, cells
      preconditioned with one hour of OGD one day prior to 5 hours of OGD, showed
      reduced lactate dehydrogenase release (p < 0.05). In conclusion, hyperglycemia
      may have specific adverse effects on endothelial cell mitochondria during
      ischemia. Preventing those effects may help to ameliorate blood-brain barrier
      disruption on reperfusion. Insights into how to prevent endothelial injury may
      come from determining the mechanisms involved in endothelial preconditioning.

PMID- 16463890
TI  - Systemic use of argatroban reduces tumor mass, attenuates neurological deficits
      and prolongs survival time in rat glioma models.
AB  - Our previous studies showed that intracerebral infusion of argatroban, a specific
      thrombin inhibitor, reduces brain edema and neurological deficits in a C6 glioma
      model. The present study investigated whether systemic argatroban administration
      can reduce glioma mass and neurological deficits and extend survival time in C6
      and F98 gliomas. Rat C6 or F98 glioma cells were infused into the right caudate
      of adult male Fischer 344 rats. Osmotic minipump loaded with argatroban (0.3
      mg/hour) or vehicle was implanted into abdomen immediately after glioma
      implantation. Tumor mass was determined at day 9. Over the period of the
      experiment, the animals underwent behavioral testing (forelimb placing and
      forelimb use asymmetry). In addition, survival time was tested in the F98 glioma
      model. In C6 glioma, argatroban reduced glioma mass (p < 0.05) and neurological
      deficits (p < 0.05) at day 9. In F98 glioma, agratroban prolonged the survival
      time (p < 0.05) and reduced the body weight loss (84 +/- 15 gram vs. 99 +/- 2
      gram in the vehicle group, P < 0.05). In conclusion, systemic use of argatroban
      reduced tumor mass and neurological deficits, and prolonged survival time. These
      results suggest that thrombin plays a key role in glioma growth and thrombin
      inhibition with argatroban may be a novel treatment for gliomas.

PMID- 16463891
TI  - Spinal contribution to CSF pressure lowering effect of mannitol in cats.
AB  - OBJECTIVES: After application of hyperosmolar mannitol the cerebrospinal (CSF)
      pressure is usually lowered within 30 min but this effect cannot be explained
      either by changes in intracranial blood volume and flow or by changes in brain
      volume. We assume that this effect of mannitol my be consequence of CSF volume
      decrease primarily in the spinal CSF due to high compliance of the spinal dura.
      METHODS: To explore such a possibility we planned to separate spinal and cerebral
      CSF. In chloralose anaesthetized cats dorsal laminectomy of C2 vertebrae was
      performed and a plastic semi ring was positioned extradurally separating cranial
      and spinal CSF. CSF pressures were recorded via cannulas positioned in lateral
      ventricle and lumbar subarachnoid space at L3 vertebrae, respectively. RESULTS:
      After intravenous bolus of 20% mannitol (0.5 or 1.0 g/kg/ 3 min) in control
      animals without cervical stenosis, the fall of both ventricular and lumbar CSF
      pressures was equal over time. At 15 min after mannitol application in cats with
      cervical stenosis an slight increase of ventricular and a fall of lumbar CSF
      pressures were observed, while at 30 min a gradient of these pressures of 5.5 and
      7 cm H2O at lower and higher dose of mannitol, respectively, were registered.
      However, after removal of cervical stenosis these gradients disappeared.
      CONCLUSION: The observed changes of CSF pressures in spinal and intracranial
      space indicate that spinal subarachnoid space contributes a great deal to overall
      fall of CSF pressure and volume in the early period after mannitol application
      probably due to high compliance of the spinal dura.

PMID- 16463892
TI  - Cell column chromatography: a new research tool to quantify cerebral cell volume
      changes following chemically-induced anoxia/re-oxygenation.
AB  - OBJECTIVE: The roles of individual types of cerebral cells in contributing to
      brain edema are undefined. The objective of this study was to determine the role
      of cerebral cell-column chromatography in quantifying cell volumes of individual
      cerebral cell lines, under chemically-induced anoxia/re-oxygenation (A/R).
      METHODS: Cerebral endothelial cells (4 experiments) or type II astrocytes (4
      experiments) were cultured to confluence on microcarrier beads. A chromatographic
      cell-column of 1.5 cm height was filled with non-treated cell-covered beads. The
      column was perfused at 1 ml/min with a balanced perfusate for one hour
      (Baseline). The perfusate was then switched to that containing 5 mM thioglycolic
      acid for one hour (Anoxia). Then the column was perfused with the normal
      perfusate for another two hours (Re-oxygenation). The total free space in the
      column, reversely reflecting cell volumes, was determined by averaged transit
      time (TTa) of a non-permeable flow tracer blue dextran. Decreased TTa means that
      cells swell, and vice versa. RESULTS: TTa in endothelial cell columns increased
      with a peak at 60 minutes of re-oxygenation. TTa in astrocyte columns decreased
      with a nadir at 30 minutes of re-oxygenation. CONCLUSION: Cell column
      chromatography can be used to determine the cerebral cell volume changes
      following chemically-induced anoxia/re-oxygenation.

PMID- 16463893
TI  - Ifenprodil treatment is associated with a down-regulation of brain aquaporin 4
      following cardiac arrest in rats.
AB  - OBJECTIVES: Ifenprodil, a NMDA receptor polyamine site antagonist, reduces
      experimental cardiac arrest (CA)-elicited brain edema, which is associated with
      an up-regulation of aquaporin 4 (AQP4), a brain water-selective channel. However,
      the interacting roles of NMDA receptors and AQP4 in CA-elicited brain edema are
      unknown. The objective of this study was to test our hypothesis that ifenprodil
      treatment is associated with a down-regulation of brain AQP4. METHODS: Twenty
      five rats were assigned to normal controls (group 1, n = 6) or subjected to eight
      minutes of asphyxial CA treated with placebo (group 2, n = 9) or ifenprodil
      (group 3, n = 10). Ifenprodil at 10 mg/kg or normal saline of equal volume was
      given intraperitoneally, 5 minutes before CA. The density of AQP4 protein and
      actin bands was scanned and expressed as the ratios of the optical density of
      AQP4 relative to that of actin. The ANOVA analysis was used to compare the group
      differences. RESULTS: The ratios of the optical density of AQP4 to that of actin
      were 0.88 +/- 0.06 in group 1, 1.11 +/- 0.08 in group 2 (p < 0.05 vs. group 1),
      and 0.78 +/- 0.04 in group 3 (p < 0.01 vs. group 2; NS vs. group 1). CONCLUSION:
      Ifenprodil given before CA is associated with a downregulation of brain AQP4 in
      rats.

PMID- 16463894
TI  - Intracerebral hemorrhage induces edema and oxidative stress and alters N-methyl-D
      aspartate receptor subunits expression.
AB  - Intracerebral hemorrhage (ICH) induces brain edema formation via a variety of
      mechanisms including toxicity due to thrombin and erythrocyte lysis. However, the
      roles of oxidative damage and excitotoxicity have not been fully elucidated and
      they are examined in this rat ICH study. Adult male Sprague-Dawley rats received
      an intracaudate injection of 100 microl autologous whole blood and 5 U of
      thrombin. Rats were sacrificed at 1 hour, 1 and 3 days, and then the brains
      processed using Western blotting to quantify N-methyl-D-aspartate receptor (NR)
      subunit expression. At 3 days, animals were also sacrificed for assessment of
      protein oxidation using Western blot analysis for dinitrophenyl (DNP) and brain
      water content. Compared to the contralateral side, ipsilateral basal ganglia NR1
      and NR2A subunit expression transiently increased at 1 hour after ICH and
      thrombin injection. From 24 hours there was a marked down-regulation. At 3 days,
      marked edema and DNP up-regulation were observed in ICH and thrombin injection
      groups. The present NR expression up-regulation at 1 hour may reflect the acute
      cell response after ICH. The down-regulation of NR subunits and upregulation of
      DNP may be associated with cell damage, towards which thrombin may contribute.

PMID- 16463895
TI  - Aging enhances intracerebral hemorrhage-induced brain injury in rats.
AB  - Age is an important factor affecting oxidative stress and plasticity after brain
      injury. The present study investigated the effects of aging on brain injury after
      intracerebral hemorrhage (ICH). Aging (18-month) and young (3-month) male Sprague
      Dawley rats received an intracerebral infusion of 100-microl autologous blood.
      Age-related changes in brain edema and neurological deficits were examined and
      heat shock protein 27 (HSP27) and heat shock protein 32 (HSP32) levels were
      determined by Western blotting. Perihematomal brain swelling was more severe in
      aged rats compared to young rats at three days after ICH (P < 0.05). The
      behavioral tests used were forelimb placing test and forelimb use asymmetry test.
      There were more severe neurological deficits and a slower recovery in aged rats
      compared to those in young rats after ICH (P < 0.05). In addition, perihematomal
      HSP27 and HSP32 protein levels were higher (p < 0.05) in aged rats. In
      conclusion, ICH causes more severe brain swelling and neurological deficits in
      aged rats. Clarification of the mechanisms of brain injury after ICH in the aging
      brain should help develop new therapeutic strategies for hemorrhagic brain
      injury.

PMID- 16463896
TI  - The antioxidant effect of N-acethylcysteine on experimental contusion in rats.
AB  - N-acethylcysteine (NAC) is known to have direct and indirect antioxidant
      abilities. We investigated the potential protective effect of NAC on ICP, brain
      edema and contusion volume after Controlled Cortical Impact (CCI) injury. A
      moderate CCI injury was induced on the left hemisphere in 48 Sprague Dawley rats.
      The animals were treated with intraperitoneal injection of NAC (163 mg/kg/KG) or
      physiological saline. Measurements of intracranial pressure (ICP) were performed
      and brains were removed at 24 hours. Gravimetric analysis of post-traumatic edema
      and morphometric measurements (TTC staining) of contusion volume were carried out
      in 24 animals, respectively. ICP measurements increased significantly over time
      with no significant differences between both groups. The relative difference in
      water content in NAC treated animals (1.45 +/- 0.1%) did not differ significantly
      versus placebo (1.47 +/- 0.2%). The contusion volume was diminished by 19% in the
      NAC group (53.52 +/- 5.3 mm3) versus placebo (66.28 +/- 4.7 mm3) without showing
      statistical significance. The antioxidant properties of NAC did not affect
      intracranial pressure or posttraumatic brain edema formation, although the
      moderate reduction of contusion volume might reveal beneficial effects on focal
      contusion.

PMID- 16463897
TI  - The investigation of cerebrospinal fluid formation by ventriculo-aqueductal
      perfusion method in cats.
AB  - OBJECTIVES: The perfusion of cerebrospinal fluid (CSF) spaces by artificial CSF
      (aCSF) containing an indicator, is an indirect method used to calculate CSF
      formation. To evaluate this method, we have developed a ventriculo-aqueductal
      perfusion method, which enables a direct measurement of CSF formation in the
      ventricles. METHODS: In chloralose anaesthetized cats, the aqueduct of Sylvius
      was cannulated so that the outflow end of the plastic cannula was positioned
      extracranially. Both lateral ventricles were also cannulated, with one cannula
      for infusion of aCSF containing blue dextrane and the other for measurement of
      CSF pressure. RESULTS: During ventriculo-aqueductal perfusion (direct method)
      under physiological CSF pressure, the outflow rate from aqueductal cannula did
      not differ significantly from the inflow rate, i.e. no CSF formation was
      observed. When the indirect method based on dilution of blue dextran in the
      outflowing perfusate was used, the formation of approximately 5 microl/min of CSF
      was obtained. CONCLUSION: Results of the direct method indicate that net CSF
      formation inside brain ventricles does not exist. The opposite results obtained
      by the indirect method questions this method as a reliable study of CSF
      formation.

PMID- 16463898
TI  - Microdialysis in traumatic brain injury--methodology and pathophysiology.
AB  - The application of clinical microdialysis to monitor changes in cerebral
      extracellular chemistry is now well established in several neurosurgical units
      worldwide. In neuro-intensive care the technique has been predominantly applied
      to patients with traumatic brain injury and subarachnoid haemorrhage. There is no
      doubt that microdialysis has increased and continues to increase our
      understanding of the pathophysiology of these conditions. Current studies are
      addressing the potential role of microdialysis as a clinical monitoring technique
      assisting in the management of patients on an intention to treat basis. This
      involves establishing the relationship between microdialysis and outcome, and the
      effect of therapeutic manoeuvres on the chemistry. This manuscript describes the
      place of microdialysis in traumatic brain injury in terms of the fundamental
      principles, methodology, pathophysiology and clinical application.

PMID- 16463899
TI  - Brain tissue oxygenation monitoring in acute brain injury.
AB  - Cerebral ischemia is one of the most important causes of secondary insults
      following acute brain injury. While intracranial pressure monitoring in the
      intensive care unit constitutes the cornerstone of neurocritical care monitoring,
      it does not reflect the state of oxygenation of the injured brain. The holy grail
      of neuromonitoring is a modality that would reflect accurately real time the
      status of oxygenation in the tissue of interest, is robust, artefact free and
      that which provides information that can be used for therapeutic interventions
      and to improve outcome. Such a device could conceivably be used to augment the
      sensitivity of current multi-modality monitoring systems in the neurocritical
      management of brain injured patients. This article examines the availability of
      data in the literature to support clinical use of local tissue oxygen probes in
      intensive care.

PMID- 16463900
TI  - Near infrared spectroscopy in brain injury: today's perspective.
AB  - The technique of near infrared spectroscopy (NIRS) is based on the principle of
      light attenuation by the chromophores oxyhaemoglobin (HbO2), deoxyhaemoglobin
      (Hb) and cytochrome oxidase. Changes in the detected light levels can therefore
      represent changes in concentrations of these chromophores. Clinical use of NIRS
      in the brain has been well established in neonates where transillumination is
      possible. While it has become a useful research tool for monitoring the adult
      brain, clinical application has been hampered by the fact that it must be applied
      in reflectance mode. This has resulted in a number of concerns, most
      significantly the issue of signal contamination by the extracranial tissue
      layers. Algorithms have been applied to try to overcome this problem, and
      techniques such as time resolved, phase resolved and spatially resolved
      spectroscopy have been developed. There has been renewed interest in NIRS as an
      easy to use, non-invasive technique for measuring tissue oxygenation in the adult
      brain. Recent technical advances have led to the development of compact, portable
      instruments that detect changes in optical attenuation of several wavelengths of
      light. Near infrared spectroscopy is an evolving technology that holds
      significant potential for technical advancement. In particular, NIRS shows future
      promise as a clinical tool for bedside cerebral blood flow measurements and as a
      cerebral imaging modality for mapping structure and function.

PMID- 16463902
TI  - Brain injury and proteomics/peptidomics: is it relevant? an overview.
AB  - Proteomics and peptidomics are different and supplemental to genomics, since in
      contrast to the basically constant genome - the proteome and peptidome are
      dynamic, constantly changing, and complex networks. Proteomics is traditionally
      linked to 2D-gel electrophoresis techniques. Concerning peptidomics, three
      different approaches are currently available, all using mass spectrometry as a
      key element. The use of proteomics or peptidomics in traumatic brain injury (TBI)
      research is demanding. From the technical point of view there are high-level
      requirements concerning the preanalytical phase, specific machinery,
      sophisticated software and skilled manpower/intellectual input. There are
      currently no bedside techniques and most methods are suitable for experimental
      TBI research in specialized laboratories. In screening experiments of CSF
      following controlled cortical impact in rats we identified several peptides,
      which, although previously known, were so far not reported in the TBI context or
      in CSF. Peptidomics and proteomics, as highly complex screening technologies,
      thus seem to carry a large potential to lead TBI science. Newly "discovered"
      peptide targets have to be validated with different methodology to establish a
      real diagnostic or therapeutic value.

PMID- 16463903
TI  - Circulating nucleic acid analysis: diagnostic applications for acute pathologies.
AB  - Much research interest has been shown in recent years for the development of
      molecular diagnostic strategies based on the analysis of DNA/RNA molecules that
      are present in the plasma/serum of human subjects. Reported applications include
      the diagnosis, prognostication or monitoring of malignancies and pregnancy
      associated complications. While researchers have speculated that cell death is a
      potential mechanism that leads to the release of DNA/RNA into the circulation,
      studies have demonstrated that indeed increased amounts of plasma DNA and RNA
      could be detected in patients sustaining acute traumatic injuries. The degree of
      plasma DNA elevation correlated with the severity of injury. Similarly, plasma
      DNA concentrations have been shown to correlate with indices of prognostic
      significance in patients with acute stroke. It is expected that new diagnostic
      markers based on plasma RNA detection could be developed for the evaluation of
      acute pathologies.

PMID- 16463901
TI  - Imaging of cerebral blood flow and metabolism in brain injury in the ICU.
AB  - The heterogeneity of the initial insult and subsequent pathophysiology has made
      both the study of human head injury and design of randomised controlled trials
      exceptionally difficult. The combination of multimodality bedside monitoring and
      functional brain imaging positron emission tomography (PET) and magnetic
      resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides
      the resource required to study critically ill patients after brain injury from
      initial ictus through recovery from coma and rehabilitation to final outcome.
      Methods to define cerebral ischemia in the context of altered cerebral oxidative
      metabolism have been developed, traditional therapies for intracranial
      hypertension re-evaluated and bedside monitors cross-validated. New modelling and
      analytical approaches have been developed.

PMID- 16463905
TI  - Partners in care.

PMID- 16463904
TI  - The Lund concept: is this logical?
AB  - The optimal therapy of sustained increase in intracranial pressure (ICP) is still
      controversial. The "Lund concept" is based on the physiological volume regulation
      of the intracranial compartments. In addition to its other functions the blood
      brain barrier (BBB) is the most important regulator of brain volume. Water
      exchange across the intact BBB is counteracted by the low permeability to
      crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5,700
      mmHg) on both sides of the BBB. If the BBB is disrupted transcapillary water
      transport will be determined by the differences in hydrostatic and colloid
      osmotic pressure between the intra- and extracapillary compartments. Under
      pathological conditions pressure autoregulation of cerebral blood flow is often
      impaired and intracapillary hydrostatic pressure will depend on variations in
      systemic blood pressure. The "Lund concept" can be summarized in four paragraphs:
      I. Reduction of stress response and cerebral energy metabolism; II. Reduction of
      capillary hydrostatic pressure; III. Maintenance of colloid osmotic pressure and
      control of fluid balance; IV. Reduction of cerebral blood volume. The efficacy of
      the treatment protocol has been evaluated in experimental and clinical studies
      regarding the physiological and biochemical (utilizing intracerebral
      microdialysis) effects. The clinical experiences have been favourable.

PMID- 16463906
TI  - Efforts under way to improve and produce new influenza vaccine.

PMID- 16463907
TI  - Extraction defect assessment, classification, and management.
AB  - Tooth extraction is a traumatic procedure initiating a complex cascade of
      biochemical and histologic events that inevitably lead to a reduction of alveolar
      bone and soft tissue. These tissue alterations often lead to an esthetic
      compromise of the future implant restoration. The hard- and soft-tissue
      architecture surrounding the extraction defect largely dictates the course of
      dental implant treatment. The EDS or extraction-defect sounding classification is
      a novel system introduced to simplify the decision-making process when planning
      for dental implant therapy following tooth extraction. Dental implant treatment
      guidelines based on the EDS classification are discussed. A review of
      pretreatment evaluations necessary to prepare for esthetic implant procedures is
      also presented.

PMID- 16463908
TI  - Bilaminar subepithelial connective tissue grafts for immediate implant placement
      and provisionalization in the esthetic zone.
AB  - Immediate implant placement and provisionalization has been considered as a
      preservative procedure when replacing failing teeth, especially in the esthetic
      zone. Nevertheless, an average facial gingival tissue recession of 1 mm is still
      common after one year of function. Furthermore, facial gingival recession of thin
      periodontal biotype seems to be more pronounced than that of thick biotype.
      Biotype conversion around both natural teeth and implants with subepithelial
      connective tissue graft has been advocated, and the resulting tissues appear to
      be more resistant to recession. A technique combining subepithelial connective
      tissue graft and immediate implant placement and provisionalization is devised to
      achieve a more stable peri-implant tissue in thin biotype situations. This
      article describes the surgical and prosthodontic approach of this procedure as
      well as its clinical rationale.

PMID- 16463909
TI  - Esthetic therapy with standard and scalloped implant designs: the five biologic
      elements for success.
AB  - The field of implant dentistry has grown significantly in recent years. Balancing
      natural-looking esthetics with long-term function, however, remains a challenging
      task. The main focus of implant dentistry is on improving the survival rate,
      simplifying the treatment, improving the esthetic outcome, and reducing the
      treatment time. Developing a natural contour and anatomically dimensioned soft
      tissue margin is critical to attaining an esthetic implant restoration. This
      article discusses the five elements to achieve natural implant esthetics: bone
      foundation, implant design and placement, soft-tissue profile, prosthetic tissue
      support, and ceramic art design.

PMID- 16463910
TI  - Implants as absolute anchorage.
AB  - Anchorage control is essential for successful orthodontic treatment. Each tooth
      has its own anchorage potential as well as propensity to move when force is
      applied. When teeth are used as anchorage, the untoward movements of the
      anchoring units may result in the prolonged treatment time, and unpredictable or
      less-than-ideal outcome. To maximize tooth-related anchorage, techniques such as
      differential torque, placing roots into the cortex of the bone, the use of
      various intraoral devices and/or extraoral appliances have been implemented.
      Implants, as they are in direct contact with bone, do not possess a periodontal
      ligament. As a result, they do not move when orthodontic/orthopedic force is
      applied, and therefore can be used as "absolute anchorage." This article
      describes different types of implants that have been used as orthodontic
      anchorage. Their clinical applications and limitations are also discussed.

PMID- 16463911
TI  - Distraction osteogensis: a surgical option for restoring missing tissue in the
      anterior esthetic zone.
AB  - Common causes of alveolar defects include bone resorption due to loss of teeth,
      infection, or trauma. There is often insufficient height or width of residual
      bone, and ridge augmentation may be required prior to implant placement. These
      defects range from small alveolar deficiencies to more complex, extensive bony
      defects. Various techniques are available for reconstructing alveolar ridges.
      Without augmentation, dental implants may have to be placed in anatomically
      unfavorable positions or have adverse angulations. These position/angulation
      compromises can lead to esthetic dissatisfaction, mechanical overload, and
      possibly implant loss. Both bone grafting and distraction osteogenesis are
      predictable methods for restoring missing tissue.

PMID- 16463912
TI  - Accuracy in the OR is nothing to sneeze at.

PMID- 16463913
TI  - Immigration and the American century.
AB  - The full impact of immigration on American society is obscured in policy and
      academic analyses that focus on the short-term problems of immigrant adjustment.
      With a longer-term perspective, which includes the socioeconomic roles of the
      children of immigrants, immigration appears as one of the defining
      characteristics of twentieth-century America. Major waves of immigration create
      population diversity with new languages and cultures, but over time, while
      immigrants and their descendants become more "American," the character of
      American society and culture is transformed. In the early decades of the
      twentieth century, immigrants and their children were the majority of the
      workforce in many of the largest industrial cities; in recent decades, the
      arrival of immigrants and their families has slowed the demographic and economic
      decline of some American cities. The presence of immigrants probably creates as
      many jobs for native-born workers as are lost through displacement. Immigrants
      and their children played an important role in twentieth-century American
      politics and were influential in the development of American popular culture
      during the middle decades of the twentieth century. Intermarriage between the
      descendants of immigrants and old-stock Americans fosters a national identity
      based on civic participation rather than ancestry.

PMID- 16463914
TI  - Trends in educational assortative marriage from 1940 to 2003.
AB  - This paper reports trends in educational assortative marriage from 1940 to 2003
      in the United States. Analyses of census and Current Population Survey data show
      that educational homogamy decreased from 1940 to 1960 but increased from 1960 to
      2003. From 1960 to the early 1970s, increases in educational homogamy were
      generated by decreasing intermarriage among groups of relatively well-educated
      persons. College graduates, in particular; were increasingly likely to marry each
      other rather than those with less education. Beginning in the early 1970s,
      however; continued increases in the odds of educational homogamy were generated
      by decreases in intermarriage at both ends of the education distribution. Most
      striking is the decline in the odds that those with very low levels of education
      marry up. Intermarriage between college graduates and those with "some college"
      continued to decline but at a more gradual pace. As intermarriage declined at the
      extremes of the education distribution, intermarriage among those in the middle
      portion of the distribution increased. These trends, which are similar for a
      broad cross section of married couples and for newlyweds, are consistent with a
      growing social divide between those with very low levels of education and those
      with more education in the United States.

PMID- 16463915
TI  - The relationship between childbearing and transitions from marriage and
      cohabitation in Britain.
AB  - In this article, we describe a general framework for the analysis of correlated
      event histories, with an application to a study of partnership transitions and
      fertility among a cohort of British women. Using a multilevel, multistate
      competing-risks model, we examine the relationship between prior fertility
      outcomes (the presence and characteristics of children and current pregnancy) and
      the dissolution of marital and cohabiting unions and movements from cohabitation
      to marriage. Using a simultaneous-equations model, we model these partnership
      transitions jointly with fertility, allowing for correlation between the
      unobserved woman-level characteristics that affect each process. The analysis is
      based on the partnership and birth histories that were collected for the 1958
      birth cohort (National Child Development Study) aged 16-42. The findings indicate
      that preschool children have a stabilizing effect on their parents 'partnership,
      whether married or cohabiting, but the effect is weaker for older children. There
      is also evidence that although pregnancy precipitates marriage among cohabitors,
      the odds of marriage decline to prepregnancy levels following a birth.

PMID- 16463916
TI  - Did fertility go up after the Oklahoma City bombing? An analysis of births in
      metropolitan counties in Oklahoma, 1990-1999.
AB  - Political and sociocultural events (e.g., Brown v. Board of Education in 1954 and
      the German reunification in 1989) and natural disasters (e.g., Hurricane Hugo in
      1989) can affect fertility. In our research, we addressed the question of whether
      the Oklahoma City bombing in April 1995, a man-made disaster, influenced
      fertility patterns in Oklahoma. We defined three theoretical orientations-
      replacement theory, community influence theory, and terror management theory-
      that motivate a general expectation of birth increases, with different
      predictions emerging from time and geographic considerations. We used two
      different empirical methodologies. First, we fitted dummy-variable regression
      models to monthly birth data from 1990 to 1999 in metropolitan counties. We used
      birth counts to frame the problem and general fertility rates to address the
      problem formally. These analyses were organized within two design structures: a
      control-group interrupted time-series design and a difference-in-differences
      design. In these analyses, Oklahoma County showed an interpretable, consistent,
      and significant increase in births. Second, we used graphical smoothing models to
      display these effects visually. In combination, these methods provide compelling
      support for a fertility response to the Oklahoma City bombing. Certain parts of
      each theory helped us organize and understand the pattern of results.

PMID- 16463918
TI  - Familial obesity as a proxy for omitted variables in the obesity-mortality
      relationship.
AB  - In a conventional survival analysis of a sample of the U.S. population in 1971
      1974, the association between mortality and obesity is compared with the
      analogous risk from the presence of an obese person in a household. The two
      factors have similar risk profiles, with a hazard ratio of 1.44 for nonmorbid
      obesity and 1.48 for nonmorbid familial obesity in one sample. If "familial
      obesity" cannot directly affect personal longevity, and if shared factors
      determine both personal and familial obesity, the mortality risk of family and
      actual personal obesity is similarly overstated. This false positive in the
      estimated risk arises from correlations among obesity and unobserved
      environmental, behavioral, or genetic factors.

PMID- 16463917
TI  - Changes in women's postmarital employment in Japan and Taiwan.
AB  - Research on female labor-force participation has not fully explained why economic
      development has different effects on married women's employment continuity across
      societies. I use life-history data from nationally representative samples of
      women in Japan and Taiwan to examine the divergence in women's patterns of labor
      force exit in these two countries during the postwar period. The findings reveal
      that the effects of family demands, occupation, firm size, and employment sector
      on women's exit rates differed substantially between Japan and Taiwan. Taken
      together, these factors account for the different trends in married women's
      employment during this period. I argue that the cross-national differences in the
      predictors of women's labor-force withdrawal reflect the extent of
      incompatibility between work and family responsibilities for married women in
      these two societies.

PMID- 16463920
TI  - AIDS mortality and the mobility of children in KwaZulu Natal, South Africa.
AB  - This paper examines the effect of parental death on the mobility of 39,163
      children aged 0-17 in rural KwaZulu Natal, South Africa, in 2000 and 2001.
      Parental mortality from all causes prior to and during follow-up increased the
      risk of a child moving by nearly two times after we controlled for the age and
      gender of the child and household characteristics. However, in the follow-up
      period, child mobility following maternal deaths from AIDS was lower than child
      mobility following maternal deaths from other causes. Younger children, boys, and
      children whose mothers or fathers were resident members of the children's
      households were also less likely to move.

PMID- 16463919
TI  - The influence of network mortality experience on nonnumeric response concerning
      expected family size: evidence from a Nepalese mountain village.
AB  - This article investigates the effects of sociometric network members' self
      reported experiences with infant mortality on nonnumeric responses regarding
      expected family size among women in a small Nepalese community. The hypotheses
      tested include (1) that uncertainty about child survival, measured as average
      infant mortality across social networks, increases the likelihood of a nonnumeric
      response and (2) that this effect will be stronger when there is less variance in
      infant mortality experience within women a networks. The results suggest that
      nonnumeric response may be related to uncertainty about mortality derived through
      social learning.

PMID- 16463921
TI  - Do conditional cash transfers influence migration? A study using experimental
      data from the Mexican PROGRESA program.
AB  - Prior research on Mexican migration has shown that social networks and economic
      incentives play an important role in determining migration outcomes. We use
      experimental data from PROGRESA, Mexico's primary poverty-reduction program, to
      evaluate the effects of conditional cash transfers on migration both domestically
      and to the United States. Our study complements a growing body of literature
      aimed at overcoming longstanding hurdles to the establishment of causal validity
      in empirical studies of migration. Analysis based on the data collected before
      and after the program's onset shows that conditional transfers reduce U.S.
      migration but not domestic migration. The data also enable us to explore the role
      of existing family and community migration networks. The results show that
      migration networks strongly influence migration, but that the effect of
      conditional transfers on migration is apparently not mediated by existing
      migration network structures. Our results suggest that conditional transfers may
      be helpful in managing rural out-migration, particularly to the United States.

PMID- 16463923
TI  - The art of caring: compassion fatigue.

PMID- 16463922
TI  - Temporal and spatial variation in age-specific net migration in the United
      States.
AB  - As fertility differences in the United States diminish, population redistribution
      trends are increasingly dependent on migration. This research used newly
      developed county-level age-specific net migration estimates for the 1990s,
      supplemented with longitudinal age-specific migration data spanning the prior 40
      years, to ascertain whether there are clear longitudinal trends in age-specific
      net migration and to determine if there is spatial clustering in the migration
      patterns. The analysis confirmed the continuation into the 1990s of distinct net
      migration "signature patterns" for most types of counties, although there was
      temporal variation in the overall volume of migration across the five decades. A
      spatial autocorrelation analysis revealed large, geographically contiguous
      regions of net in-migration (in particular, Florida and the Southwest) and
      geographically contiguous regions of net out-migration (the Great Plains, in
      particular) that persisted over time. Yet the patterns of spatial concentration
      and fragmentation over time in these migration data demonstrate the relevance of
      this "neighborhood" approach to understanding spatiotemporal change in migration.

PMID- 16463924
TI  - The ABCs of sun protection for children.
AB  - Excessive sun exposure in childhood is a critical variable influencing skin
      cancer risk. Nurses must teach parents how to properly protect their children
      from excessive sun exposures by demystifying UV radiation and teaching proper sun
      protection measures. Protecting children from excessive sun exposure, while not
      curtailing recreation, should be the goal of all nurses caring for children.

PMID- 16463925
TI  - Advances in deep chemical peels.
AB  - Deep chemical peels have been used in dermatology for more than a century and
      their popularity increased dramatically during the past decade. The main
      indications for this procedure include photoaging, perioral wrinkling, acne
      scars, and precancerous skin lesions. Deep chemical peel is a nonsurgical
      procedure that compares favorably with other surgical and nonsurgical procedures
      for skin rejuvenation, such as surgical face-lifting, dermabrasion, and laser
      resurfacing. It is a safe and cost-effective method that provides significant
      results and a high degree of patient satisfaction.

PMID- 16463926
TI  - What's your assessment? Drug eruption.

PMID- 16463928
TI  - Living with pityriasis rubra pilaris.

PMID- 16463927
TI  - Pityriasis rubra pilaris: a clinical review.
AB  - Pityriasis rubra pilaris is a skin condition with many different clinical
      presentations. History, histology, clinical presentation, its different
      classified forms, treatments, and differential diagnoses are reviewed.

PMID- 16463929
TI  - Skin infection with Fusarium.

PMID- 16463930
TI  - Pityriasis rubra pilaris.

PMID- 16463931
TI  - Diseases of the epidermis: pityriasis rosea, lichen planus, keratosis pilaris.

PMID- 16463932
TI  - A Christmas 'complement' Carol.

PMID- 16463936
TI  - Universal health plan in Wisconsin could boost capitation.
AB  - A proposal to create a dollars 13.5 billion all-payer health care system under
      capitation in Wisconsin is getting positive reviews from payers, hospitals, and
      doctors.

PMID- 16463935
TI  - IPA predicts comeback for risk contracts in Milwaukee.

PMID- 16463937
TI  - Health economist makes the case for aligning incentives under capitation.
AB  - Integrated delivery systems that accept risk-adjusted capitated dollars are best
      suited to provide high quality and cost-efficient care, according to a new
      report.

PMID- 16463938
TI  - Physician use of EMRs varies depending on type of organization.
AB  - A new survey shows that physician use of electronic health records is lower than
      expected, but the rate of EHR use depends on the type and size of the health care
      organization.

PMID- 16463939
TI  - Remote surgicenter experience with hernia repair.
AB  - A remote outpatient surgicenter was planned and constructed with three partner
      groups-76 physicians and two competing hospitals. The CFS was opened in July 1994
      and has since performed a large volume of procedures: >124,800 total and, in
      2003, 14,900 cases. This multispecialty center during that same period of time
      (1994 to date) has performed 2659 hernia operations. Patients were discharged
      home in 1-2 hours after surgery to be followed as outpatients in the physician's
      office. Only six patients were admitted to the hospital. This efficient and
      economic model is well suited for hernia repair in the selected adult and
      pediatric patient population without a significant number of adverse events. The
      community has readily accepted this program for adult and pediatric hernia
      repair. Patients, family members, referring physicians, and participating
      physicians have endorsed and recommended the program.

PMID- 16463940
TI  - Surgical adhesion development and prevention.

PMID- 16463941
TI  - Are meshes with lightweight construction strong enough?
AB  - The use of mesh has become essential in the repair of abdominal wall incisional
      hernias. Suture techniques, reapplied after failure of a primary repair, are
      characterized by recurrence rates of up to 50 percent, whereas the reinforcement
      of the abdominal wall with surgical mesh has significantly decreased these rates
      to <10 percent. This article describes the background for the development of mesh
      with lightweight construction and physiological biomechanical performance.

PMID- 16463942
TI  - Interactive biomaterials: taking surgery to the next level.
AB  - Medicine has been advanced greatly by implantable biomaterials, but today's
      standard materials are not without problems. Infection, erosion, adhesions,
      persistent pain, and other complications suggest that something better is
      possible. Just as normal tissues self-renew, it is desirable to have an implant
      recapitulate original anatomy for both structure and function. Short of complete
      tissue regeneration, perhaps an implant material could transition from an
      inanimate bridge to a living tissue with strong similarity to the original host
      architecture-to optimize the biology and not simply the mechanics of tissue
      repair. Such remodelable or tissue-inductive materials exist today and are in use
      in a wide variety of surgical applications. Changing the idea that implants must
      be rigid, inert, and permanent to an understanding that implants can provide
      short-term mechanics and long-term repair by harnessing the host's healing
      abilities represents a paradigm shift that will ultimately benefit patients and
      the practice of surgery.

PMID- 16463943
TI  - Comparison of three different mesh materials in tension-free inguinal hernia
      repair: prolene versus Vypro versus surgisis.
AB  - Using mesh or a synthetic prosthesis during tension-free inguinal hernia repair
      has been shown to be safe and effective. We compared the final outcome in
      treating inguinal hernia in 45 patients using three different prosthetic
      materials: 15 patients underwent tension-free inguinal hernia repair using
      Prolene (polypropylene) mesh, 15 using Vypro (polyglactin and polypropylene)
      mesh, and 15 with Surgisis-a new bioactive material derived from porcine small
      intestinal submucosa. The aim of this study was to evaluate the safety and
      efficacy of tension-free inguinal repair using Surgisis, comparing it with
      conventional prosthetic materials. From January 2003 to December 2003, 45 male
      patients underwent Lichtenstein inguinal hernia repair. Median follow-up was 12
      months, with a range of 1-16 months. Each patient underwent ultrasound evaluation
      of the inguinal region 1 month after surgery. All the procedures were completed
      under local anesthesia. There were no intraoperative complications, and all
      patients were discharged home the same day of surgery. No recurrent hernias and
      wound infections were observed in our post-operative follow-up period.
      Postoperative pain (visual analog score) and discomfort were lower in patients
      with Surgisis mesh. There was no statistically significant difference between the
      groups in terms of overall early and late complications; however, there was a
      tendency toward a higher incidence of pain and discomfort in Vypro and Prolene
      group. The median time to full recovery was significantly shorter in the Surgisis
      group. Surgisis mesh seems to be a promising new prosthetic material for hernia
      repair. Long-term follow-up is necessary to confirm these preliminary results.

PMID- 16463945
TI  - Absorbable and nonabsorbable barriers on prosthetic biomaterials for adhesion
      prevention after intraperitoneal placement of mesh.

PMID- 16463944
TI  - Cross-linked acellular porcine dermal collagen implant in laparoscopic ventral
      hernia repair: case-controlled study of operative variables and early
      complications.
AB  - Cross-linked acellular porcine dermal collagen matrix (CPDC) is a new biological
      implant for use in hernia repair. This study compares operative variables and
      early complications of all laparoscopic ventral hernia repair (LVHR) procedures
      by a single surgeon using CPDC to a historical cohort from the same surgeon using
      composite polypropylene and expanded polytetrafluoroethylene mesh (PP/ePTFE).
      Eighty-four and 55 patients, respectively, initially underwent attempted LVHR
      with composite and CPDC prostheses. There was no significant difference between
      the two groups in the incidence of hernia recurrence. Severe foreign body
      response with or without mesh infection was noted in three composite group
      patients, with enterocutaneous fistula in one of these; all mandated removal of
      the mesh. The referring surgeon removed the CPDC implant in one case upon
      diagnosis of wound infection. CPDC is safe for use in LVHR and offers an
      alternative to composite PP/ePTFE mesh that warrants further investigation.

PMID- 16463946
TI  - Inguinal hernia repair with Spermatex: the first 100 cases.
AB  - We evaluated 100 consecutive cases of surgical repair of inguinal hernia using
      SpermaTex (Davol, Cranston, RI) to assess postoperative outcome measures of early
      and late complications and hernia recurrence. SpermaTex is a bilayer surgical
      mesh prosthesis consisting of a fibrosis-inducing layer of polypropylene mesh
      bonded to a fibrosis-inhibiting layer of expanded polytetrafluoroethylene. One
      hundred male patients with unilateral primary inguinal hernia, with a mean age of
      49 years, underwent hernia repair with the open anterior approach using
      SpermaTex. Mean operative time was 35 minutes; there was 3% morbidity and no
      mortality. At a 14-day follow-up, no patients had postoperative pain; within 2-8
      weeks, all patients had returned to their presurgical health condition, with no
      inguinal pain. At follow-ups of 3 months to 4 years, all 100 patients experienced
      no recurrence, and all had improved, although 3 patients developed chronic sinus
      tracts. This series shows a favorable postoperative outcome profile for the use
      of SpermaTex in inguinal hernia repair.

PMID- 16463947
TI  - Postmesh herniorrhaphy wound infections: can they be eliminated?
AB  - The present infection rate of 3 to 4% for inguinal herniorrhaphy should be
      considered unacceptable. Modern understanding of bacterial film formation,
      dynamics, and molecular composition should allow the performance of virtually
      infection-free inguinal and ventral herniorrhaphy. In our service, the
      reinstitution of accepted and time-tested aseptic regimens combined with
      antiseptic measures consisting of 1 gram of intravenous cefazolin administered 1
      hour before surgery plus frequent wound irrigations with a solution of 80 mg of
      gentamycin sulphate dissolved in 250 ml of normal saline solution have yielded an
      infection rate of 0.11% in over 4,000 clean inguinal and 350 clean ventral
      herniorrhaphies. Our last wound infection occurred in 1983. These results
      supporting the experience of orthopedic joint replacement suggest that very low
      postherniorrhaphy infection rates are achievable goals.

PMID- 16463948
TI  - Spontaneous free perforation of the distal ileum in Crohn's disease: case study.
AB  - Free perforation of the intestine in Crohn's disease is an uncommon occurrence,
      with an incidence of 1% to 3% in Western countries. This report describes a case
      of free perforation of the distal ileum caused by Crohn's disease, in which
      resection and primary anastomosis was performed. The medical records of the case
      were reviewed. The patient presented acutely with free perforation of the distal
      ileum secondary to previously undiagnosed Crohn's disease. Postoperatively 13
      days, the patient's course was complicated by anastomotic leakage and abscess
      formation. After drainage, subtotal colectomy, and re-anastomosis, primary
      abdominal closure was achieved using collagen matrix derived from porcine dermis.
      Resection and primary anastomosis is widely considered the preferred treatment
      for perforated small bowel. This case describes the successful treatment of an
      associated anastomotic complication that uses porcine dermal collagen to achieve
      primary closure and rapid recovery.

PMID- 16463949
TI  - Laparoscopic ventral hernia repair--managing and preventing complications.
AB  - Laparoscopic ventral hernia repair was first reported over 10 years ago. Since
      that time, the procedure has gained widespread acceptance as an appropriate
      option for the management of ventral hernias of all types. Most published series,
      including one multicenter study of >800 cases, document that the procedure is
      safe and effective with low recurrence and wound complication rates. In studies
      comparing laparoscopic ventral hernia repair to open techniques, the majority
      show the benefit of the laparoscopic approach in terms of recurrence rates, wound
      complication rates, and length of hospital stay. The laparoscopic approach does,
      however, lend itself to potential complications that may be more likely or more
      difficult to deal with compared with open techniques. This paper will describe
      these specific complications, including potential disasters, with strategies to
      manage them, or hopefully, avoid them altogether.

PMID- 16463950
TI  - Laparoscopic ventral hernia repair without sutures--double crown technique: our
      experience after 140 cases with a mean follow-up of 40 months.
AB  - It has been reported that avoidance of recurrences after laparoscopic ventral
      hernia repair (LVHR) depends on using sutures to secure the mesh. We developed a
      successful sutureless LVHR. The "Double Crown" LVHR using ePTFE mesh (overlap, 23
      cm) was done in 140 cases. Tacks were placed 1 cm apart at the edge of the mesh.
      A second crown of tacks was placed at the edge of the defect. Three conversions
      (2.14%) and five bowel perforations occurred intraoperatively (3.57%).
      Postoperative complications were prolonged ileus (two cases), hematoma (two
      cases), seroma requiring drainage (three cases), and reoperation in one case for
      mesh intolerance, three cases for bowel perforation, and one case for small bowel
      ischemia. The recurrence rate (mean follow-up of 40 months) was 2.14%. The Double
      Crown LVHR is a safe alternative to LVHR using sutures, with a similar recurrence
      rate, less pain, fewer incisions and infections, and a shorter operating time.

PMID- 16463952
TI  - Aligning incentives to promote quality care: lessons from pay-for-performance
      initiatives.
AB  - Pay-for-performance has been a hot-button topic this year. The federal
      government, hospitals, private employers, insurers, physician groups, and many
      others have been looking at numerous ways to align financial incentives with high
      quality healthcare. And now, the results are coming in.

PMID- 16463951
TI  - Transperitoneal view of the PROLENE hernia system open mesh repair.
AB  - The PROLENE Hernia System (PHS), consisting of an onlay and an underlay patch
      with a connector, has recently been introduced as an option for tension-free open
      repair of inguinal hernias and is touted for the repair of both direct and
      indirect hernias. In theory, the underlay is placed either through the internal
      ring or through the transversalis fascia and is seated in the preperitoneal
      space. To date, there have been no views of how this underlay is seated after
      open repair. Our objective was to determine the position and orientation of the
      underlay patch after open repair. After informed consent, two patients requiring
      both umbilical and inguinal hernia repairs had their inguinal hernias repaired
      using the open technique with the PHS. In the first patient, after open inguinal
      repair, the umbilical hernia was reduced, a 30 degrees laparoscope was placed
      intraperitoneally, and the underlay patch placed in the retroperitoneal space was
      visualized through the translucent peritoneum. In the second patient, the
      umbilical hernia was initially reduced, and the laparoscope was introduced to
      visualize the creation of the preperitoneal space and placement of the underlay
      during open repair of the inguinal hernia. As per our hypothesis, we show that
      the preperitoneal space is successfully created during open repair with the PHS
      with minimal trauma. More importantly, the underlay is deployed open and contours
      to the shape of the abdominal wall from the native intra-abdominal pressure,
      covering regions at risk for future herniation.

PMID- 16463953
TI  - Seeking a just culture to design a safer hospital environment.
AB  - If a hospital employee makes a mistake and a patient is hurt, should that
      employee be punished, fired, or considered blame-free? With a "Just Culture"
      framework in place at a hospital, the answer in most instances should be "none of
      the above." According to David Marx, JD, the design of the health system and the
      behavior of the employee at the time of the incident--and not simply the incident
      itself--should come under review.

PMID- 16463954
TI  - Making the medical clipboard a thing of the past: commission releases report on
      Ending the Document Game.
AB  - A new report, Ending the Document Game, released this fall by the Commission on
      System Operability is built around "three aspects of transformation:" how to get
      physicians and caregivers to use technology systems, interoperability, and
      connectivity.

PMID- 16463955
TI  - JCAHO announces Ninth Annual Codman Award winners.

PMID- 16463956
TI  - A study on the investigation of cadmium chloride genotoxicity in rat bone marrow
      using micronucleus test and chromosome aberration analysis.
AB  - In this study, we investigated the genotoxic and cytotoxic potential of cadmium
      chloride (CdCl2) in Wistar rat tibia bone marrow cells, using the structural
      chromosomal aberration (SCA) and micronucleus (MN) test systems. CdCl2 was
      administered to adult female rats as repeated i.p. doses of 0.5 mg/kg b.w. for 18
      week (four months) at 48 h intervals. Mitomycin C (MMC) was used as a positive
      control (2 mg/kg b.w.). This study shows that cadmium chloride treatment
      significantly induced the frequency of micronucleus in polychromatic erythrocytes
      in tibia bone marrow. This increase in micronucleus frequency shows that cadmium
      has a genotoxic effect on bone marrow at this level. Also, in order to determine
      cytotoxicity in bone marrow, the ratio of polychromatic erythrocytes to
      normochromatic erythrocytes was calculated in bone marrow. The results of this
      study indicate that CdCl2 decreased this ratio. The decrease of this ratio in
      bone marrow shows CdCl2 may lead to cytotoxicity. We have reported that 0.5 mg/kg
      level chronic exposure to cadmium (Cd) has an injurious effect on bone marrow.
      Our findings indicate that CdCl2 has a cytotoxic and genotoxic effect on rat bone
      marrow at chronic exposure.

PMID- 16463958
TI  - Fluorosis and its hematological effects.
AB  - Although it has been reported that fluoride ingestion has no influence on various
      indices of hematopoiesis, some research has been published that excessive
      fluoride developed anemia and eosinophilia of leukocytes. Isparta is situated on
      the lake region of Turkey where fluorosis is endemic. Our aim was to explore the
      hematological effects in rats induced by fluoride. In this study, Wistar-Albino
      rats were used, divided into two groups as control and fluorized. While the
      control group was administered commercial water (including 0.07 ppm fluoride),
      the fluorized group was administered 100 ppm fluoride in commercial drinking
      water for four months. At the end of four months, hematological indices (Hb, Hct,
      MCV, MCH, RDW, RBC, WBC, and platelet counts) were measured. In addition, bone
      marrow samples were investigated. Mean leukocyte counts (WBC) in the control
      group and fluorized group were 7.07 (2.62-12.25) and 2.76 (3.13-5.24)x 10(3)/mm3,
      respectively. We observed displastic changes on granulocytes in the bone marrow
      samples of the fluorized group. Although there were significant statistical
      changes in WBC, we did not determine red blood cell and platelet changes in the
      fluorized group.

PMID- 16463957
TI  - Effect of formaldehyde inhalation on Hsp70 in seminiferous tubules of rat testes:
      an immunohistochemical study.
AB  - One parameter which might provide an insight into the underlying mechanism of the
      effect of formaldehyde (FA) inhalation on testicular tissue, is the assessment of
      heat shock protein 70 (Hsp70), which increases promptly in cells exposed to
      stress caused by chemical toxicity. Thus, following subchronic exposure at
      cytotoxic concentrations, we studied the immunohistochemical effect of FA
      inhalation on changes in Hsp70 content in testicular tissue. We used 18 albino
      Wistar rats divided into three groups, exposed to 0 (control), 5 and 10 ppm FA
      gas for a total of 91 days, 8 h/day, five days a week. Serum testosterone levels
      were determined using a chemiluminescent enzyme immunoassay. Testicular tissues
      were stained with Hematoxylin-Eosine and Hsp70 immunohistochemically performed.
      Diameters of seminiferous tubules and serum testosterone levels in animals
      inhaling FA were significantly decreased. In seminiferous epithelium stained for
      Hsp70, compared to those in the control group, the spermatogenetic cells in the
      experimental groups demonstrated an obvious increase in immunoreaction
      spermatides in the adluminal region and especially in the cytoplasm of
      spermatocytes. Immunoreaction of Hsp70 was detected in the spermatogonias of
      animals exposed to FA inhalation as opposed to those of the control group.
      Compared to the control, there was a significant increase in the immunoreactions
      observed not only in the cytoplasm of primary spermatocytes, but also spermatides
      in the adluminal region of the seminiferous tubules. In conclusion, FA gas may
      damage spermatogenetic cells and increase Hsp70 synthesis.

PMID- 16463959
TI  - Concentrations of nano and related ambient air pollutants at a traffic sampling
      site.
AB  - A micro-orifice uniform deposit impactor (MOUDI) and a nano-MOUDI were used to
      measure the atmospheric coarse (PM2.5 -10), fine (PM2.5), ultrafine (PM0.056-1)
      and nano (<0.056 microm) particle concentrations and size distributions at a
      traffic sampling site in winter in central Taiwan, from November 2004 to January
      2005. Concentrations of metallic elements (Fe, Mg, Cr, Zn, Pb, Cu) and major ion
      (SO4(2-), NO3(-), NH4(+)) in particles of various sizes (nano, ultrafine, fine
      and coarse) were measured. Ambient air particulates generally exhibited a bimodal
      size distribution in the range 0.056-10 microm. The results show that the
      concentrations followed the order, Fe>Mg>Cr>Zn>Pb> Cu in PM10, fine, ultrafine
      and nano-sized particles. Moreover, the data showed that the average metallic
      elements Fe and Zn have similar concentration distributions: the concentration
      decreased as the particle size fell in the nano size range.

PMID- 16463960
TI  - Cancer incidence among male military and civil pilots and flight attendants: an
      analysis on published data.
AB  - Flight personnel are exposed to cosmic ionizing radiation, chemicals (fuel, jet
      engine exhausts, cabin air pollutants), electromagnetic fields from cockpit
      instruments, and disrupted sleep patterns. Only recently has cancer risk among
      these workers been investigated. With the aim of increasing the precision of risk
      estimates of cancer incidence, follow-up studies reporting a standardized
      incidence ratio for cancer among male flight attendants, civil and military
      pilots were obtained from online databases and analysed. A meta-analysis was
      performed by applying a random effect model, obtaining a meta-standardized
      incidence ratio (SIR), and 95% confidence interval (CI). In male cabin
      attendants, and civil and military pilots, meta-SIRs were 3.42 (CI = 1.94-6.06),
      2.18 (1.69-2.80), 1.43 (1.09-1.87) for melanoma; and 7.46 (3.52-15.89), 1.88
      (1.23-2.88), 1.80 (1.25-2.58) for other skin cancer, respectively. These tumors
      share as risk factors, ionizing radiation, recreational sun exposure and
      socioeconomic status. The meta-SIRs are not adjusted for confounding; the
      magnitude of risk for melanoma decreased when we corrected for socioeconomic
      status. In civil pilots, meta-SIR was 1.47 (1.06-2.05) for prostate cancer. Age
      (civil pilots are older than military pilots and cabin attendants) and disrupted
      sleep pattern (entailing hyposecretion of melatonin, which has been reported to
      suppress proliferative effects of androgen on prostate cancer cells) might be
      involved. In male cabin attendants, meta-SIR was 21.5 (2.25-205.8) for Kaposi's
      sarcoma and 2.49 (1.03-6.03) for non-Hodgkin's lymphoma. AIDS, which was the most
      frequent single cause of death in this occupational category, likely explains the
      excess of the latter two tumors.

PMID- 16463961
TI  - Effects of S6-strain Mycoplasma gallisepticum inoculation at ten, twenty-two, or
      forty-five weeks of age on the performance characteristics of commercial egg
      laying hens.
AB  - Experimental inoculation of commercial laying hens, maintained under controlled
      conditions, with the S6-strain of Mycoplasma gallisepticum (S6MG) at 10 wk of age
      has previously been shown to affect the lengths and weights of various portions
      of the reproductive tract without affecting subsequent performance. Two trials
      were conducted to compare the effects of S6MG inoculation at 10 wk of age (prior
      to lay), 22 wk of age (onset of lay), and 45 wk of age (during lay) on
      performance characteristics in commercial layers housed and maintained under
      controlled conditions, as in previous studies. In each trial, BW, mortality, egg
      production, egg weight, eggshell weight per unit of surface area, percentage
      eggshell weight, percentage albumen weight, percentage yolk weight, and yolk
      weight per albumen weight ratio were examined at various ages throughout an
      entire laying cycle. Across wk 47 and 58 (age periods after the last 45 wk
      inoculation), eggshell weight per unit of surface area and percentage eggshell
      weight were significantly reduced in birds that had received an S6MG inoculation
      at 45 wk of age when compared with birds that had not received an S6MG
      inoculation or had been inoculated with S6MG at either 10 or 22 wk of age.
      Alterations in eggshell quality in response to S6MG may become evident only in
      older birds that are experiencing declines in production when housed under
      controlled conditions.

PMID- 16463962
TI  - Effects of feeding grains naturally contaminated with Fusarium mycotoxins on
      hepatic fractional protein synthesis rates of laying hens and the efficacy of a
      polymeric glucomannan mycotoxin adsorbent.
AB  - Experiments were conducted to evaluate the effects of feeding grains naturally
      contaminated with a combination of Fusarium mycotoxins on hepatic fractional
      protein synthesis rates (FSR) of laying hens. Thirty-six 32-wk-old laying hens
      were fed diets formulated with 1) uncontaminated grains, 2) contaminated grains,
      or 3) contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent for a
      period of 4 wk. Hepatic FSR were measured in vivo by the flooding-dose method.
      The feeding of contaminated grains decreased hepatic FSR in laying hens compared
      with controls after 4 wk. The hepatic FSR of birds fed contaminated grains and
      contaminated grains + glucomannan mycotoxin adsorbent were not different. It was
      concluded that the in vivo hepatic FSR of laying hens was inhibited by the
      feeding of grains naturally contaminated with Fusarium mycotoxins and that this
      may explain some of the adverse effects seen when contaminated grains were fed to
      laying hens.

PMID- 16463963
TI  - Adrenocortical responses of Japanese quail to a routine weighing procedure and to
      tonic immobility induction.
AB  - Tonic immobility (TI) is induced by brief manual restraint, and it is a commonly
      used test of fearfulness, particularly in poultry. However, in view of increasing
      ethical concerns about experimentation on living animals, there is a need to
      ensure that the tests used do not elicit unacceptable distress. In the United
      Kingdom, there is some debate as to whether TI should be classified as a
      regulated experimental procedure that requires a Home Office license to
      experiment on living animals under the Animals (Scientific Procedures) Act of
      1986. The present study compared plasma corticosterone (PC) concentrations in
      undisturbed Japanese quail (controls) with those exposed to the induction of TI
      or those exposed to a routine weighing procedure. Circulating PC concentrations
      were higher following TI induction or weighing than in the controls, but the 2
      treatments elicited similar adrenocortical responses. Further, the PC levels
      found here were lower than those reported elsewhere when quail were exposed to
      crating, transport, or mechanical immobilization stressors. We therefore
      concluded that the induction of TI might be best regarded as a mild stressor.
      Furthermore, studies using this technique can identify ways of alleviating fear
      and thereby improving well-being. Collectively, we believe that the use of TI is
      justified, and it does not require classification as a regulated procedure in the
      United Kingdom or elsewhere.

PMID- 16463964
TI  - Microsatellite markers associated with resistance to Marek's disease in
      commercial layer chickens.
AB  - The objective of the current study was to identify QTL conferring resistance to
      Marek's disease (MD) in commercial layer chickens. To generate the resource
      population, 2 partially inbred lines that differed in MD-caused mortality were
      intermated to produce 5 backcross families. Vaccinated chicks were challenged
      with very virulent plus (vv+) MD virus strain 648A at 6 d and monitored for MD
      symptoms. A recent field isolate of the MD virus was used because the lines were
      resistant to commonly used older laboratory strains. Selective genotyping was
      employed using 81 microsatellites selected based on prior results with selective
      DNA pooling. Linear regression and Cox proportional hazard models were used to
      detect associations between marker genotypes and survival. Significance
      thresholds were validated by simulation. Seven and 6 markers were significant
      based on proportion of false positive and false discovery rate thresholds less
      than 0.2, respectively. Seventeen markers were associated with MD survival
      considering a comparison-wise error rate of 0.10, which is about twice the number
      expected by chance, indicating that at least some of the associations represent
      true effects. Thus, the present study shows that loci affecting MD resistance can
      be mapped in commercial layer lines. More comprehensive studies are under way to
      confirm and extend these results.

PMID- 16463965
TI  - Estimation of heritability for fluctuating asymmetry in chickens by restricted
      maximum likelihood. Effects of age and sex.
AB  - The purposes of the present study were to estimate the heritability of the
      fluctuating asymmetry in chickens, using the restricted maximum likelihood
      procedure, and to evaluate the effects of age and sex on the fluctuating
      asymmetry. Leg, wing, and feather lengths and ear-lobe and wattle areas were
      measured. In experiment 1, 1,073 birds were used from 2 generations with complete
      pedigree of the Quail Castellana breed to estimate the heritability for the
      fluctuating asymmetry at 36 wk of age. The estimated heritability of absolute
      fluctuating asymmetry was not significantly different from zero for all 5 traits,
      and similar estimates were obtained for relative fluctuating asymmetry,
      directional asymmetry, transformed absolute and relative fluctuating asymmetry,
      and 3 alternative indexes of fluctuating asymmetry. The heritability of the
      combined absolute or relative fluctuating asymmetry was still very low,
      indicating that fluctuating asymmetry was determined solely by environmental
      sources of variation and that fluctuating asymmetry estimates should not be
      confounded by appreciable additive genetic contributions. The genetic correlation
      between sides was not significantly different from one, indicating that
      differences between sides were purely environmental in origin. Different traits
      rarely showed much correlation in their level of fluctuating asymmetry,
      indicating that the level of fluctuating asymmetry in all traits did not reflect
      equally the quality of animals. In experiment 2, fluctuating asymmetry
      differences among ages and sexes were investigated at 8, 12, 16, 20, 24, 28, 32,
      36, and 40 wk in 360 birds from the same breed. Significant variation with age
      was observed in leg length, wing length, feather length (females), and wattle
      area (females), which was mainly related to onset of sexual maturity and adult
      stage. Females showed significantly greater fluctuating asymmetry for ear-lobe
      area than males. There were significant differences in fluctuating asymmetry for
      wing length, feather length, and wattle area near the onset of sexual maturity,
      with males having significantly greater fluctuating asymmetry than females for
      wing length and the opposite being true for feather length and wattle area.

PMID- 16463966
TI  - Effects of feed-borne Fusarium mycotoxins on hematology and immunology of
      turkeys.
AB  - Feeding grains naturally-contaminated with Fusarium mycotoxins has been shown to
      alter the metabolism and performance of turkeys. The objectives of the current
      experiment were to examine the effects of feeding turkeys with grains naturally
      contaminated with Fusarium mycotoxins on their hematology and immunological
      indices (including functions), and the possible protective effect of feeding a
      polymeric glucomannan mycotoxin adsorbent (GMA). Two hundred twenty-five 1-d-old
      male turkey poults were fed corn, wheat, and soybean meal-based starter (0 to 3
      wk), grower (4 to 6 wk), developer (7 to 9 wk), and finisher (10 to 12 wk) diets
      formulated with uncontaminated grains, contaminated grains, or contaminated
      grains with 0.2% GMA. The chronic consumption of Fusarium mycotoxins caused minor
      and transient changes in hematocrit (0.33 L/L) and hemoglobin (10(6) g/L)
      concentrations as well as in blood basophil (0.13 x 10(9)/L) and monocyte counts
      (3.42 x 10(9)/L) compared with controls. Supplementation of the contaminated diet
      with GMA prevented these effects on blood cell counts. Biliary IgA concentrations
      were significantly increased (4.45-fold) when birds were fed contaminated grains
      compared with controls, but serum IgA concentrations were not affected. Contact
      hypersensitivity to dinitrochlorobenzene, which is a CD8+ T-cell-mediated delayed
      type hypersensitivity response, was decreased (48%) by feed-borne mycotoxins
      compared with the control. By contrast, the primary and secondary antibody
      response to sheep red blood cells, a CD4+ T-cell-mediated response, was not
      affected. It was concluded that chronic consumption of grains naturally
      contaminated with Fusarium mycotoxins exerts only minor adverse effects on the
      hematology and some immunological indices of turkeys. Consumption of grains
      naturally contaminated with Fusarium mycotoxins may, however, increase the
      susceptibility of turkeys to infectious agents against which CD8+ T cells play a
      major role in defense.

PMID- 16463967
TI  - Feeding high levels of lupine seeds to broiler chickens: plasma micronutrient
      status in the context of digesta viscosity and morphometric and ultrastructural
      changes in the gastrointestinal tract.
AB  - This work examines the effects of lupine-based diets on the status of the host's
      riboflavin and zinc. Test diets contained 35% soybean meal (control) or raw (40%)
      or dehulled (35%) lupine seed meal and were isocaloric (13.4 MJ of AME/kg) and
      isonitrogenous (23% crude protein). Each diet was offered ad libitum to a group
      of 16 male commercial broiler chicks for 21 d, starting at 1 d of age. Broilers
      fed lupine diets had lower feed intakes and growth rates. All sections of the
      intestinal tract were significantly enlarged (P < 0.01) in all groups fed lupine
      based diets in comparison with broilers fed the soybean meal diet, but there were
      no differences in the morphologies of the mucosa, submucosa, muscularis, or
      serosa. Increased size of the duodenum, jejunum, and ileum was predominantly
      attributed to the increase in length rather than intestinal tissue mass. Hence,
      the enlargement of the intestinal tract was consistent with physiological
      hyperplasia and not pathological remodeling and hypertrophy. Overall, broilers
      fed lupine-based diets had more viscous digesta than those fed the soybean meal
      diet, but the differences were statistically not significant. Blood plasma Zn
      concentration did not differ between broilers fed lupine-based diets and those
      fed soybean-meal-based diets, and all broilers fed lupine-based diets had
      significantly higher (P < 0.001) riboflavin concentrations. In this context, it
      is apparent that the bioavailability of these micronutrients from lupine diets is
      not compromised. Intestinal tissue hyperplasia may be interpreted as
      physiological adaptation to increase absorptive capacity and thus maximize
      absorption of essential nutrients in the face of antinutritional factors in the
      diet.

PMID- 16463968
TI  - Effect and interactions of dietary sodium and chloride on broiler starter
      performance (hatching to twenty-eight days of age) under subtropical summer
      conditions.
AB  - One-day-old Starbro male broiler chicks (n = 360) were used to determine the
      effect of increasing levels of Na+ and Cl- above the NRC (1994) recommendations
      for growing broilers diets (hatching to 28 d) in extremely hot weather. The
      average maximum and minimum temperatures recorded were 39 and 32 degrees C,
      respectively. An average relative humidity was 58.2% during the experimental
      period. Three levels of dietary Na+ (0.20, 0.25, and 0.30%) and Cl- (0.30, 0.40,
      and 0.50%) were used in 3 x 3 factorial arrangement while maintaining a dietary
      electrolyte balance (DEB) of 250 mEq/kg. Higher weight gain (P < 0.002) and
      maximum water consumption (P < 0.05) were observed for birds fed diets containing
      0.25 and 0.30% Na+, respectively. Litter moisture was significantly higher (P <
      0.05) for birds fed diets containing 0.25% Na+ and 0.40 and 0.50% Cl-. High
      dietary Na+ (0.30%) tended to increase breast yield (P < 0.003) and decreased
      abdominal fat (P < 0.001). There was no effect of Na+ on blood pH or serum HCO3-.
      Diets containing 0.40% Cl- increased the dressing percentage (P < 0.001) and leg
      yield (P < 0.001) and decreased serum HCO3- (P < 0.001). There was no effect of
      dietary Cl- on blood pH, feed intake, weight gain, feed:gain, water intake,
      water:feed intake, or mortality. Significant dietary effect of Na+ x Cl- was
      noted only for litter moisture (P < 0.001), dressing percentage (P < 0.05),
      breast (P < 0.05) and leg (P < 0.001) yields, abdominal fat (P < 0.002), and
      serum HCO3- (P < 0.001). Birds fed diet containing 0.25% Na+ and 0.30% Cl-
      performed as well as those fed other diets when the cyclic temperature ranged
      from 32 to 39 degrees C.

PMID- 16463969
TI  - Effects of feeding ervil (Vicia ervilia) seeds soaked in water or acetic acid on
      performance and internal organ size of broilers and production and egg quality of
      laying hens.
AB  - Experiment 1 was conducted to study the effects of feeding 60% untreated ervil
      seeds (UE) or ervil soaked in water at room temperature (RTWE) or at 40 degrees C
      (40WE) for 72 h with water change every 12 h on the performance and internal
      organ size of broilers. Isocaloric and isonitrogenous corn-soybean meal diet
      (control) and diets containing 60% UE, RTWE, or 40WE were fed to battery caged
      broilers in 4 replicates with 8 birds per replicate, from 8 to 49 d. Broilers
      consuming UE from 8 to 28 d gained less weight, used feed less efficiently, and
      had heavier liver, pancreas, and gall bladder weights (%BW) than the other
      treatments (P < 0.05). Compared with control birds, broilers on 40WE had similar
      relative organ weights, except for kidney, but lower BW gain at 49 d (P < 0.05).
      In experiment 2, ervil seeds were soaked in 1% acetic acid at room temperature
      (RTAAE) or at 40 degrees C (40AAE) for 24 h. A conventional diet and diets
      containing 60% UE, 40WE, RTAAE, or 40AAE were fed to individually caged laying
      hens in 4 replicates per treatment with 5 hens per replicate for 42 d. Hens on UE
      had the poorest performance followed by RTAAE, 40WE, and then 40AAE (P < 0.05).
      Compared with the control, all treated ervil diets resulted in lower shell
      thickness values but higher Haugh unit scores (P < 0.05). In experiment 3, 30%
      dietary UE and 40AAE at 10, 20, and 30% were fed to layers for 56 d. The general
      performance of hens on 30% 40AAE was comparable with that of the control except
      for BW and feed conversion (P < 0.05). Compared with UE, the performance of
      broilers and layers was improved by 40WE and that of hens was further enhanced by
      40AAE. In addition, diets containing up to 20% 40AAE had no adverse effects on
      feed conversion, egg production, or quality of hens.

PMID- 16463970
TI  - Analysis of myosin isoform transitions during growth and development in diverse
      chicken genotypes.
AB  - The temporal expression of chicken skeletal fast myosin heavy chain (MyHC)
      isoforms in pectoralis major muscle was characterized in 3 commercial broiler
      lines at embryonic d 19 and at 7, 14, and 21 d posthatch. Lines A and B have been
      selected for breast yield, and line C is a fast' growing commercial line with
      limited selection for carcass traits. The isoform transitions in breast muscle
      samples were compared with samples from Single Comb White Leghorns (line D) using
      a semiquantitative immunoassay. The hypothesis was that selection for growth and
      carcass development in broilers would be accompanied by changes in the temporal
      expression of one or more of the chicken fast MyHC isoforms. Embryos from all
      lines were sampled at 19 d of incubation, and chicks were randomly sampled at 7,
      14, and 21 d post-hatch. Myosin was extracted from pectoralis major muscle and
      assayed for purity and total protein concentration by SDS-PAGE and bincinchoninic
      acid protein analyses, respectively. The relative concentration of MyHC isoforms
      was evaluated by semiquantitative ELISA with 3 monoclonal antibodies specific for
      chicken skeletal fast embryonic and adult (eMyHC, aMyHC; EB165), neonatal (nMyHC;
      2E9), and adult (aMyHC; AB8) myosin, respectively. The overall temporal
      expression of the myosin isoforms, eMyHC, nMyHC, and aMyHC, was similar in all
      lines. With eMyHC, at 19 d of incubation, line B had lower expression than lines
      A, C, and D. Expression of nMyHC, in lines C and D was similar with expression
      being highest at 7 d and lower at 14 d and 21 d. In lines A and B, however, nMyHC
      expression was higher at hatch than lines C and D. In line D, aMyHC was expressed
      at 14 d and increased through 21 d, whereas in lines A, B, and C, aMyHC isoform
      was expressed and was higher at 7 d and increased through 21 d. The results of
      this experiment support our hypothesis that commercial broilers have different
      temporal expression patterns of the developmental chicken fast MyHC isoforms.

PMID- 16463971
TI  - The effect of pre- and postmolt diets high in n-3 fatty acids and molt programs
      on skeletal integrity and insulin-like growth factor-I of White Leghorns.
AB  - This study investigated changes in bone integrity and circulating concentrations
      of insulin-like growth factor-I (IGF-I) of hens subjected to 2 distinct molting
      regimens and fed pre- and postmolt diets high in n-3 or n-6 fatty acids. A dual
      energy x-ray absorptiometer determined bone mineral density (BMD) of the tibia
      and humerus of 45 live hens from 62 to 76 wk of age. Densitometric scans were
      also conducted in excised tibia and humerus at 66, 71, and 76 wk of age.
      Concentrations of IGF-I were monitored using an homologous RIA at the same ages.
      The molting treatments consisted of 10 d of fasting + cracked corn for 7 d +
      pullet developer diet for 10 d or a nonfasting molt (wheat-middlings-based diet
      for 27 d). Five weeks prior to and after either molt treatment, birds were fed 1
      of 2 diets containing dietary n-6/ n-3 fatty acids ratios of 0.6 or 8.0. At the
      end of the molt (71 wk of age), tibial BMD decreased 30% in fasted and 11% in
      nonfasted molt regimens, and the fatty acid content of the premolt diet had no
      effect on the decline in BMD. The BMD of the humerus also decreased during molt
      with the exception of hens subjected to a nonfasted molt and fed n-3 fatty acid
      diets in which their BMD values were similar to or greater (at 73 wk of age) than
      those of controls during the entire experimental period (treatment by bone by
      age, P < or = 0.0001). Induced molt affected circulating IGF-I concentrations
      (treatment by age interaction, P < or = 0.0001), and the response was the same
      regardless of molt regimen (fasting vs. nonfasting) or diet (n-3 vs. n-6 fatty
      acids). A decrease in IGF-I 54 h postmolt was noted; however, from 13 to 43 d
      postmolt, all molted birds had elevated IGF-I as compared with controls. In
      conclusion, a nonfasted molt as compared with fasted molt was less detrimental to
      bone mineralization; dietary n-6/n-3 fatty acid ratios in the pre- and postmolt
      diets had little effect on the decline of skeletal integrity during molt, and
      circulating IGF-I concentrations were affected by molt.

PMID- 16463972
TI  - Melengestrol acetate in experimental diets as an effective alternative to induce
      a decline in egg production and reversible regression of the reproductive tract
      in laying hens. I. Determining an effective concentration of melengestrol
      acetate.
AB  - Induced molting increases egg quality and egg production and extends the
      productive life of hens. Molting is accomplished by feed withdrawal, which has
      been criticized for not addressing hen well-being, and current alternatives have
      resulted in poor postmolt performance and inadequate well-being. Molting leads to
      regression of follicles on the ovary and causes loss of steroidogenic support for
      the oviduct, leading to cessation of lay. Melengestrol acetate (MGA), an orally
      active progestin, may decrease support for the ovary, resulting in loss of
      support for the oviduct, while hens are fed a balanced diet. In this experiment,
      a dose response study, Hy-Line W-36 hens were fed 0, 0.1, 1, 4, or 8 mg of MGA
      per hen/d in a balanced diet for 28 d and then returned to a normal diet. Four
      birds on d 0 and 4 birds per treatment on d 1, 2, 4, 8, 12, 16, 20, 24, 28, 32,
      36, 40, and 44 were euthanized. The weight of the ovary with follicles, magnum,
      shell gland, and oviduct were determined. A decrease in egg production was
      observed in those groups receiving 4 and 8 mg of MGA, until removal of MGA from
      the diet. After d 28, egg production increased to the production level of hens
      fed 0, 0.1, or 1 mg of MGA. The weight of the ovary with follicles, oviduct,
      magnum, and shell gland were unchanged throughout in groups fed 0, 0.1, or 1 mg
      of MGA. However, groups fed 4 or 8 mg of MGA exhibited a decrease (P < 0.05) in
      the weight of the ovary with follicles, oviduct, magnum, and shell gland until d
      28. Recrudescence of the large yellow follicles as well as rejuvenation of the
      oviduct and its components, the magnum and shell gland, in the 4 and 8 mg MGA
      groups occurred by d 44. Melengestrol acetate, fed to hens on a balanced layer
      diet, caused reversible regression of follicles and, therefore, removal and
      return of support for the oviduct.

PMID- 16463973
TI  - Melengestrol acetate as an effective alternative to induce a decline in egg
      production and reversible regression of the reproductive tract in laying hens.
      II. Effects on postmolt egg quality.
AB  - Induced molting increases egg quality and egg production and extends the
      productive life of hens. Molting is accomplished by feed withdrawal, which has
      received criticism, and alternatives described thus far result in poor postmolt
      performance. Melengestrol acetate at a dosage of 4 or 8 mg/d, in a balanced diet,
      leads to reversible regression of the reproductive tract. However, this
      alternative must also increase egg quality after rest to be considered an
      adequate method by the industry. Hy-Line W-36 (n = 497) laying hens were assigned
      randomly to a diet containing 0 mg of melengestrol acetate (MGA; control)
      throughout the experiment or 4 or 8 mg of MGA/d for 2, 4, or 6 wk. Upon reaching
      50 and 70% lay, after MGA removal, eggs were collected for measurements of egg
      quality, including Haugh units (i.e., internal egg quality), shell thickness, and
      breaking strength (i.e., external egg quality). Haugh units were greater (P <
      0.05) for eggs laid by hens molted with a diet containing 8 mg of MGA for all
      durations compared with controls. Shell thickness was greater (P < 0.05) when
      hens were treated with 4 mg of MGA for 6 wk and 8 mg of MGA for 4 and 6 wk
      compared with control. Egg breaking strength was greater (P < 0.05) than controls
      for all hens fed MGA, regardless of dosage or duration of feeding. A subset of
      hens was fed 8 mg of MGA per hen/d for 2 wk, and eggs were collected for 3 wk.
      Seven days after MGA was removed from the diet, the amount of MGA in the yolk was
      below the level of detection of the assay, and the concentration found in the
      eggs at all time points was 3 orders of magnitude below the Food and Drug
      Administration's tolerance for MGA in edible tissue. When used as an alterative
      method to induce a rest, MGA leads to an increase in the internal and external
      egg quality of hens compared with nonmolted hens.

PMID- 16463975
TI  - Recovery of bacteria from broiler carcass respiratory tracts before and after
      immersion scalding.
AB  - Occlusion of the trachea and decapitation were compared with a conventional
      unilateral neck cut for effects on bacteria entering into the respiratory tract
      of broiler carcasses during scalding. In experiment 1, the trachea was occluded
      prior to the carcass entering the scalder to determine if bacterial recovery from
      the respiratory tract could be diminished. The first carcass was removed at the
      end of bleeding, and a plastic cable tie was placed around the neck of a second
      carcass and tightened to occlude the trachea. After proceeding through the triple
      tank immersion scalder, the second carcass (trachea occluded) was removed, and a
      third carcass (without the trachea occluded during scalding) was removed. In
      experiment 2, after being stunned, carcasses were unilaterally bled or
      decapitated. Unilaterally bled and decapitated carcasses were removed at the end
      of bleeding and after scalding. In both experiments, trachea were cannulated, and
      respiratory tract rinses were collected. For experiment 1, the numbers of
      bacteria recovered (log10 cfu/mL of rinse) from prescald nonoccluded carcass
      respiratory tract rinses were 2.5 Escherichia coli, 2.6 coliforms, and 3.2 total
      aerobes. Respiratory tract rinses from carcasses sampled postscald (without
      occluding the trachea) had higher bacteria numbers at 4.6 E. coli, 5.0 coliforms,
      and 5.4 total aerobes. Respiratory tract rinses from carcasses with the trachea
      occluded prior to scalding had the lowest number of bacteria at 1.9 E. coli, 2.3
      coliforms, and 2.7 total aerobes. In experiment 2, the numbers of bacteria
      recovered from respiratory tract rinses of unilaterally bled or decapitated
      carcasses did not differ prescald or postscald, although all postscald values
      were higher (P < 0.05). Results confirmed that bacteria numbers increased within
      the respiratory tract during immersion scalding, the increase could have been
      prevented by occluding the trachea prior to scalding, and decapitation did not
      alter the number of bacteria recovered from respiratory tract rinses prior to or
      following immersion scalding.

PMID- 16463974
TI  - Biochemical characteristics and sperm production of turkey semen in relation to
      strain and age of the males.
AB  - The effect of turkey strain [BUT (Big-6), Hybrid Large White (HLW), and Nicholas
      (N-700)] on semen quantitative parameters (ejaculate volume, sperm concentration,
      and total number of sperm) and biochemical parameters (seminal plasma protein
      concentration, acid phosphatase activity in spermatozoa and seminal plasma, and
      antiproteinase activity of seminal plasma) was investigated over the reproductive
      period. The Big-6 strain had better quantitative parameters of semen compared
      with HLW and N-700 strains. Besides protein concentration, the Big-6 strain had
      the highest level of acid phosphatase activity in semen and antiproteinase
      activity in seminal plasma. The N-700 strain was characterized by reduced
      quantitative parameters and the lowest levels of all biochemical parameters in
      semen. While quantitative parameters of semen showed very little trend over the
      21 wk of the reproductive season, the biochemical parameters increased several
      fold. Biochemical parameters of semen seemed to be more affected than
      quantitative parameters by age of the males. These changes may be related to
      decreasing semen quality with increasing age of male turkeys.

PMID- 16463976
TI  - Effects of extended storage on egg quality factors.
AB  - Eggs were collected from a single inline processing facility weekly for 3 wk
      (replicates). The eggs were stored at 4 degrees C and 80% RH. Sampling began the
      day after collection and continued each week for 10 wk. During analysis, 24 eggs
      were examined for egg weight, albumen height, Haugh units (HU), shell strength,
      and vitelline membrane strength for each replicate. Egg weight decreased (P <
      0.0001) from approximately 61 to 57 g after 10 wk of storage. Eggs from the
      second replicate were significantly (P < 0.0001) heavier than the other
      replicates by an average of 3 g. On average, albumen height decreased with
      extended storage (P < 0.0001) from 7.05 to 4.85 mm. Albumen height was
      approximately 0.2 mm higher for the eggs in replicate 2 compared with the other
      replicates (P < 0.01). Haugh unit values decreased during cold storage from 82.59
      to 67.43 (P < 0.0001). There were no differences between replicates for HU
      values. No differences were detected for shell strength between replicates or
      during extended storage. A significant difference (P < 0.05) was found in
      detectable vitelline membrane strength between replicates, but this difference
      was less than 0.05 g. The elasticity of the vitelline membrane decreased during
      storage (P < 0.01) remaining low after 6 wk. Extended cold storage led to
      decreases in egg weight, albumen height, and HU. However, average HU values were
      still within the range for grade A. Shell strength was not affected by extended
      storage. Vitelline membrane elasticity also decreased, which could lead to yolks
      more easily rupturing as consumers crack the eggs. The results indicated that
      although the physical quality factors monitored in this study decreased during
      storage, egg quality was still acceptable beyond current recommended shelf life
      guidelines.

PMID- 16463977
TI  - Efficacy of electrolyzed water in the prevention and removal of fecal material
      attachment and its microbicidal effectiveness during simulated industrial poultry
      processing.
AB  - This study was undertaken to investigate the efficacy of alkaline and acidic
      electrolyzed (EO) water in preventing and removing fecal contaminants and killing
      Campylobacter jejuni on poultry carcasses under simulated industrial processing
      conditions. New York dressed and defeathered chicken carcasses spot-inoculated
      with cecal material or C. jejuni were subjected to spraying treatment with
      alkaline EO or 10% trisodium phosphate (TSP) water or combinations of spraying
      and immersion treatments with acidic EO and chlorinated water, respectively.
      Prespraying chicken carcasses with alkaline EO water significantly lowered cecal
      material attachment scores (3.77) than tap water (4.07) and 10% TSP (4.08) upon
      treatment of the dorsal area. Combinations of pre- and postspraying were
      significantly more effective than postspraying only, especially when using
      alkaline EO water in removing fecal materials on the surface of chicken
      carcasses. Although treatment by immersion only in EO and chlorinated water
      significantly reduced the initial population (4.92 log10 cfu/g) of C. jejuni by
      2.33 and 2.05 log10 cfu/g, respectively, combinations of spraying and immersion
      treatment did not improve the bactericidal effect of sanitizers. The results
      indicated that alkaline EO water might provide an alternative to TSP in
      preventing attachment and removal of feces on the surface of chicken carcasses.
      The results also suggested that chicken carcasses containing pathogenic
      microorganisms may contribute to the cross-contamination of whole batches of
      chickens during processing in the chiller tank and afterward.

PMID- 16463978
TI  - Evaluation of slower-growing broiler genotypes grown with and without outdoor
      access: meat quality.
AB  - Consumer interest in organic and natural poultry products raised with outdoor
      access is growing. An experiment was conducted to assess the effects of outdoor
      access and genotype on meat quality. One slow-growing genotype (S), 2 medium
      growing genotypes (M1 and M2), and a commercial fast-growing genotype (F) were
      raised (straight-run) for 81, 67, or 53 d, respectively. The placement date was
      staggered in order to achieve a similar final body weight. Each genotype was
      assigned to 3 pens of 24 birds each and raised in indoor floor pens in a
      naturally ventilated facility; the S and F genotypes were also assigned to 2
      floor pens with outdoor access containing 36 birds each. All birds were provided
      with the same starter, grower, and finisher feeds, and birds were commercially
      processed. Pectoralis samples were collected at 6 h postmortem for proximate
      analysis and evaluation of meat quality. The principal effect of outdoor access
      was to make the meat more yellow in the case of the S genotype (P < 0.05)
      although not the F genotype (P > 0.05). Drip loss and cook loss (%) were affected
      (P < 0.05) by genotype, with the highest losses occurring with the S genotype and
      the lowest losses occurring with the F and M genotypes. Tenderness was affected
      (P < 0.05) by gender as well as production system but only in the F birds.
      Pectoralis dry matter (%), fat (%), and ash (%) were largely unaffected (P >
      0.05) by genotype or outdoor access. These data indicate that meat quality
      differences exist among genotypes with very different growth rates and reared
      with or without outdoor access.

PMID- 16463979
TI  - Effect of irradiating shell eggs on quality attributes and functional properties
      of yolk and white.
AB  - Shell eggs were irradiated and the physico-chemical, and functional properties of
      egg yolk and white were determined. The color of egg yolk was not affected, but
      the viscosity of egg white was dramatically lowered and became watery by
      irradiation. The foam capacity and foam stability of egg white were significantly
      decreased due to protein oxidation by irradiation. However, the texture
      characteristics of egg white were not changed by irradiation, indicating that
      irradiation may not alter the thermal characteristics of egg white proteins.
      Sulfur volatiles were generated by irradiation but disappeared during storage
      under aerobic conditions. Because egg white became watery, irradiation may not be
      advisable for table eggs but may be useful for pasteurizing liquid egg white or
      liquid whole egg without significant deterioration of their quality and
      functionality. In particular, the dramatic decrease in the viscosity of egg white
      by irradiation will improve flow of liquid egg white or liquid whole egg, which
      could be highly useful for egg processing.

PMID- 16463980
TI  - Use of water spray and extended drying time to lower bacterial numbers on soiled
      flooring from broiler transport coops.
AB  - Broiler transport coops soiled with Campylobacter-positive feces have been shown
      to facilitate cross-contamination of broilers. Washing and sanitizing coop
      surfaces do not always effectively eliminate bacteria. The objective of this
      study was to examine drying as a means of lowering bacterial numbers on transport
      coop flooring. Small squares (5 x 5 cm) of fiberglass flooring from transport
      coops were intentionally contaminated with 1 g of Campylobacter-positive broiler
      gut contents. Soiled floor squares were sprayed with water and allowed to dry for
      15 min, 24 h, or 48 h. Unsprayed squares were examined at each time period as
      controls. All squares were sampled by cotton-tipped applicators that were
      cultured for Campylobacter, coliforms, and Escherichia coli. Sampling of
      unsprayed squares at 15 min yielded 7.3 log cfu of Campylobacter, 6.2 log cfu of
      coliforms and 5.9 log cfu of E. coli per floor square. Water spray alone resulted
      in a significantly lower number of organisms recovered: 4.1 log cfu
      Campylobacter, 3.6 log cfu coliform, and 3.2 log cfu E. coli per floor square.
      When water spray was followed by a 24-hour drying period, no Campylobacter,
      coliforms, or E. coli were detected on the floor surface. However, allowing
      unsprayed soiled flooring to simply dry for 24 or 48 h also resulted in no
      recovery of Campylobacter and very low numbers of coliforms and E. coli. A 24- or
      48-hour drying period for fecal matter on broiler transport cage flooring may be
      a viable method to lower bacterial numbers on these surfaces.

PMID- 16463981
TI  - Antimicrobial susceptibility of environmental Staphylococcus aureus strains
      isolated from a pigeon slaughterhouse in Italy.
AB  - No information is available concerning the antimicrobial susceptibility of
      Staphylococcus aureus isolated from pigeon slaughterhouses. In the present study,
      59 staphylococcal strains isolated from a pigeon slaughterhouse in central Italy
      were compared according to their antibiotic resistance. On the basis of cultural
      and biochemical properties, all isolates could be identified as S. aureus. The
      strains were checked for the productions of enterotoxins A, B, C, D by reversed
      passive latex agglutination. Resistance to 26 antibiotics was also determined
      paying particular attention to resistance to those antimicrobial agents
      frequently used in human medicine and in poultry breeding. Only one strain was
      positive for the production of enterotoxins type C and D. It was isolated from
      the evisceration tube after slaughtering. Enterotoxin B was produced by 2 strains
      isolated from the eyebrows and conjunctivas of the worker operating the crop
      rinsing tube. As to the susceptibility to antibiotics, all strains were sensitive
      to amoxicillin/clavulanic acid, bacitracin, cephalothin, fusidic acid,
      gentamicin, kanamycin, linezolid, oxacillin, quinupristin/dalfopristin,
      rifampicin, tobramycin, trimethoprim-sulfamethoxazole, vancomycin. Some (15.2%)
      of the strains were resistant to ampicillin and to penicillin G; 6.8% were
      resistant to chloramphenicol, 20.3% to enrofloxacin, 16.9% to erythromycin and to
      ciprofloxacin, 8.5% to clindamycin, and 11.9% to lincomycin. The highest
      percentages of strains were resistant to tetracycline and oleandomicin (37.3 and
      25.4% respectively). Methicillin-resistant staphylococci were also found (3.4%).
      Only one strain had a multiple antibiotic resistance index > 0.30. The results
      were statistically analyzed and clustered in 6 groups. This work provides the
      antibiotic resistance pattern of S. aureus strains isolated from a pigeon
      slaughtering plant and represents a study on a quite unknown field in meat
      production.

PMID- 16463982
TI  - Evaluation of hypertrophic obstructive cardiomyopathy by exercise stress
      echocardiography. New methodology.
AB  - Exercise echocardiography with image acquisition during treadmill exercise is the
      most common form of stress testing used in our department. The usual evaluation
      of patients with hypertrophic obstructive cardiomyopathy consists of serial
      echocardiographic studies at rest. The purpose of this study was to evaluate
      intraventricular gradients during exercise echocardiography in patients with a
      diagnosis of hypertrophic obstructive cardiomyopathy. We studied 13 patients, 8
      male, mean age 56 +/- 9 years Intraventricular gradients were measured using
      continuous wave Doppler; two evaluations were performed at rest: one in left
      lateral decubitus and the other in orthostatic position after one minute in this
      position. The patients then underwent a treadmill exercise test using the
      modified Bruce protocol, during which intraventricular gradients were measured at
      peak exercise. Finally, a further measurement was taken in the first 90 seconds
      of the recovery period in left lateral decubitus. The intraventricular gradient
      in left lateral decubitus was 54 +/- 29 mmHg; in orthostatic position 69 +/- 30
      mmHg (p < 0.001 versus gradient in left lateral decubitus); at peak exercise 109
      +/- 47 mmHg (p < 0.001 versus gradient in orthostatic position); and during
      recovery in left lateral decubitus 78 +/- 33 mmHg (p < 0.001 versus gradient at
      peak exercise in orthostatic position). We conclude that intraventricular
      gradients increase significantly in orthostatic position and increase
      considerably during treadmill exercise testing. The gradients measured in the
      recovery period do not reflect what happens during effort or therefore during
      these patients' daily activities. This type of evaluation can help us to better
      understand the pathophysiology of patients with a diagnosis of hypertrophic
      obstructive cardiomyopathy and to optimize treatment.

PMID- 16463983
TI  - Exercise stress testing in hypertrophic cardiopathy: a change of attitude is
      needed.

PMID- 16463984
TI  - Performance of the Colson MAM BP 3AA1-2 automatic blood pressure monitor
      according to the European Society of Hypertension validation protocol.
AB  - OBJECTIVE: To evaluate the performance of the Colson MAM BP 3AA1-2 oscillometric
      automatic blood pressure monitor according to the validation protocol of the
      European Society of Hypertension, testing its suitability for self-measurement of
      blood pressure. The performance of the device was assessed in relation to various
      clinical variables, including age, gender, body mass index, arm circumference and
      arterial stiffness. METHOD: 33 subjects (15 men and 18 women), with a mean age of
      47 +/- 10 years, were studied according to the procedures laid down in the
      European Society of Hypertension validation protocol. Sequential same-arm blood
      pressure measurements were made, alternating between a mercury standard and the
      automatic device. The differences among the test-control measurements were
      assessed and divided into categorization zones of 5, 10 and 15 mmHg discrepancy.
      Aortic pulse wave velocity was assessed in all subjects with a Complior device
      (Colson, Paris). RESULTS: The Colson MAM BP 3AA1-2 passed all three phases of the
      protocol for both systolic and diastolic blood pressure. The mean differences
      between the test and control measurements were -1.0 +/- 5.0 mmHg for systolic
      blood pressure and -1.1 +/- 4.1 mmHg for diastolic blood pressure. Both standard
      deviations are well below the 8 mmHg limit proposed by the Association for the
      Advancement of Medical Instrumentation. The predictive value of various clinical
      variables for the discrepancies was assessed by a regression model analysis, with
      no variable being found that independently undermined the performance of the
      monitor. In another regression analysis, we found a similar relation between test
      and control blood pressures and aortic pulse wave velocity, a widely recognized
      and validated index of target organ damage. CONCLUSIONS: These data show that the
      Colson MAM BP 3AA1-2 satisfies the quality requirements proposed by the European
      Society of Hypertension, demonstrating its suitability for inclusion in
      integrated programs of clinical surveillance based on self-measurement of blood
      pressure. The uniformity of its performance over a wide spectrum of clinical
      characteristics and the relation found with pulse wave velocity further reinforce
      its clinical validity.

PMID- 16463985
TI  - Cardiac resynchronization therapy with sequential biventricular pacing: impact of
      echocardiography guided VV delay optimization on acute results.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves left ventricular
      synchrony as evaluated by tissue Doppler imaging (TDI), leading to improved left
      ventricular performance and reverse remodeling. New CRT devices enable
      programming of left and right VV delay. The aim of this study was to determine
      whether sequential biventricular (BiV) pacing by echo-guided programming of VV
      delay would enhance the response to CRT. METHODS: 15 consecutive patients with
      severe heart failure and left bundle branch block underwent CRT by BiV device
      implantation. They were studied with conventional and TDI echo the day before
      implantation. Left ventricular ejection fraction (LVEF) was determined, and the
      electromechanical delay (QS), defined as the time interval from the beginning of
      the QRS to the S wave in pulsed TDI, was assessed in each of the four left
      ventricular basal segments. The dyssynchrony index was calculated as the
      difference between the longest and shortest electromechanical delay (QS(max
      min)). The parameters were re-evaluated the day after implantation during
      simultaneous BiV pacing and with seven different VV delays. The optimal VV delay
      was determined by finding the VV interval corresponding to the maximum aortic
      velocity time interval (VTI). RESULTS: QS(max-min) decreased from 85.3 +/- 27.0
      msec to 46.7 +/- 23.0 msec (p = 0.0002), LVEF increased from 21.7 +/- 7.3% to
      30.0 +/- 7.7% (p = 0.0001) and aortic VTI increased from 12.7 +/- 3.6 cm to 15.2
      +/- 4.0 cm (p < 0.0001), with simultaneous BiV pacing. The VV intervals were
      programmed as follows: LV pre-excitation by 10 msec in five patients, 20 msec in
      three, 30 msec in two, and 40 msec in three; and RV pre-excitation by 10 msec in
      one and by 20 msec in one. The maximal aortic VTI obtained with VV delay
      programming increased from 15.2 +/- 4.0 cm to 17.7 +/- 4.0 cm (p = 0.0005).
      During optimized sequential BiV pacing, QS(max-min) further decreased from 46.7
      +/- 23.0 msec to 30.6 +/- 21.0 msec (p = 0.02) and LVEF further increased from
      30.0 +/- 7.7% to 35.0 +/- 7.7% (p = 0.0003). CONCLUSIONS: Sequential BiV pacing
      with VV delay optimized by evaluation of aortic VTI enhanced the response to CRT
      with additional improvements in left ventricular synchrony and left ventricular
      function compared to simultaneous CRT.

PMID- 16463987
TI  - Impact of acute ischemia-reperfusion on myocardial mitochondrial function in an
      ex-vivo model of global myocardial ischemia.
AB  - INTRODUCTION: Cardiac mitochondria, as the major source of energy used by the
      heart, play an important part in the survival of cardiomyocytes undergoing
      ischemia followed by reperfusion. During ischemia, cardiac mitochondria represent
      one of the main cellular defense mechanisms, acting as a calcium-sequestering
      system and maintaining levels of energy production. However, when these cellular
      mechanisms are overcome, loss of mitochondrial integrity leads not only to the
      breakdown of energy production, but also to the release of pro-apoptotic factors,
      thus compromising the survival of cardiac cells. OBJECTIVES: To study the impact
      of acute ischemia-reperfusion (IR) on myocardial mitochondrial function in an ex
      vivo model of global ischemia. METHODS: Wistar rat hearts were divided into two
      groups: control (165 minutes of perfusion with Krebs-Henseleit solution) and
      ischemia-reperfusion (IR - 10 minutes perfusion, followed by 35 minutes ischemia
      and 120 minutes reperfusion). Various parameters of mitochondrial function were
      assessed: respiratory control ratio (RCR) using a Clark-type oxygen electrode,
      oxidative stress (using the thiobarbituric acid reactive substances [TBARS]
      test), and mitochondrial swelling amplitude and calcium uptake, both determined
      by fluorimetric methods. RESULTS: All mitochondrial parameters were severely
      affected by IR. The IR group showed a significant decrease in RCR, which was
      independent of the respiratory substrate used, for each assay. There were no
      significant differences between the two experimental groups in TBARS production.
      The control group showed a trend for a decrease in mitochondrial swelling
      amplitude and an increase in calcium uptake compared to the IR group, in both the
      absence and presence of cyclosporin A. CONCLUSIONS: In this study, IR
      significantly altered mitochondrial function (RCR, mitochondrial swelling
      amplitude and intramitochondrial calcium uptake). This means that during acute
      myocardial ischemia, every effort should be made to avoid reperfusion injury,
      given its deleterious consequences for coronary artery disease patients.

PMID- 16463986
TI  - Activation profile of pro-inflammatory cytokines in acute cardiac overload.
AB  - INTRODUCTION: Pro-inflammatory cytokines have been implicated in ventricular
      remodeling during heart failure progression. In the present study, we
      investigated the effects of acute volume and RV pressure overload on
      biventricular hemodynamics and myocardial gene expression of IL-6 and TNF-alpha.
      METHODS: Male Wistar rats (n = 45) instrumented with RV and LV tip
      micromanometers were randomly assigned to one of three protocols: i) acute RV
      pressure overload (PrOv) induced by pulmonary trunk banding in order to double RV
      peak systolic pressure, for 120 or 360 min; ii) acute volume overload (VolOv)
      induced by dextran40 infusion (5 ml/h), for 120 or 360 min; iii) Sham. Free wall
      samples from the RV and LV were collected for mRNA quantification. RESULTS: In
      the RV, acute overload induced IL-6 and TNF-alpha gene expression, higher in
      VolOv (IL-6: + 669.7 +/- 263.4%; TNF-alpha: + 5149.9 +/- 1099.0%; 360 min) than
      in PrOv (IL-6: + 64.9 +/- 44.2%; TNF-alpha: + 628.1 +/- 229.3%; 360 min). In
      PrOv, TNF-alpha mRNA levels in the LV were increased, in the absence of
      ventricular overload. IL-6 and TNF-alpha mRNA levels did not correlate in the LV,
      while in the RV a positive correlation was found (r = 0.574; p < 0.001).
      CONCLUSIONS: Acute cardiac overload induces overexpression of pro-inflammatory
      cytokines. This gene activation is not uniform, being higher in volume overload
      and involving both load-dependent and load-independent mechanisms.

PMID- 16463988
TI  - Intraventricular gradient during effort in a professional soccer player. Clinical
      significance.
AB  - The authors report the case of a 20-year-old professional soccer player who
      underwent medical evaluation because of atypical chest discomfort and dizziness
      precipitated by strenuous effort. The ECG and echocardiogram findings were
      normal. The young athlete did a treadmill stress test which was negative for
      myocardial ischemia. His myocardial perfusion imaging and coronary angiography
      were also normal. Later during the investigation, he underwent treadmill stress
      echocardiography, during which he developed an intraventricular gradient of over
      100 mmHg with end-systolic peak and systolic anterior movement (SAM) of the
      mitral valve. These echocardiographic findings were not present at rest and
      disappeared shortly after termination of exercise. The authors discuss the
      significance of these findings and their potential link to sudden death.

PMID- 16463989
TI  - Economic evaluation of drug-eluting stents in coronary angioplasty.
AB  - Coronary angioplasty has revolutionized the treatment of coronary artery disease,
      from the first balloon angioplasty to the current era of drug-eluting stents
      (DES), which were developed to eliminate the bare metal stent's (BMS) Achilles'
      heel, restenosis. DES have an extremely low restenosis rate but are significantly
      more expensive and need more prolonged dual antiplatelet therapy. Restenosis has
      a generally benign prognosis and is not associated with higher mortality or major
      adverse cardiovascular events, which has limited the penetration of DES, whose
      only advantage is the reduction of restenosis. Economic evaluation of DES is
      therefore of paramount importance for assessing their appropriate use. In
      randomized trials in which they are compared with BMS, economic evaluation is
      advantageous for DES, with good cost-effectiveness ratios for both cost per
      quality-adjusted life year (QALY) and cost per revascularization avoided.
      However, these trials have two major limitations--the angiographic follow-up
      protocol and selection of patients with lower risk--and so their results do not
      accurately reflect reality. Other studies with unselected populations and cost
      effectiveness models show that there is an economic advantage in the use of DES
      in groups with higher risk of restenosis, but not for the whole population
      undergoing angioplasty. Use of DES will be more appropriate if we can identify
      populations with a higher likelihood of restenosis, because these are the
      patients that will benefit most from their use and in whom they will be
      economically advantageous.

PMID- 16463990
TI  - Coronary aneurysm and acute myocardial infarction.

PMID- 16463991
TI  - Coronary sinus pacing in a patient with a tricuspid prosthesis.
AB  - We present images of a permanent pacing lead implanted in the coronary sinus of a
      patient with a tricuspid prosthesis.

PMID- 16463992
TI  - Metastatic spinal tumors.
AB  - Metastatic spinal tumors are the most common type of malignant lesions of the
      spine. Prompt diagnosis and identification of the primary malignancy is crucial
      to overall treatment. Numerous factors affect outcome including the nature of the
      primary cancer, the number of lesions, the presence of distant nonskeletal
      metastases, and the presence and/or severity of spinal cord compression. Initial
      management consists of chemotherapy, external beam radiotherapy, and external
      orthoses. Surgical intervention must be carefully considered in each case.
      Patients expected to live longer than 12 weeks should be considered as candidates
      for surgery. Indications for surgery include intractable pain, spinal cord
      compression, and the need for stabilization of impending pathological fractures.
      Whereas various surgical approaches have been advocated, anterior-approach
      surgery is the most accepted procedure for spinal cord decompression. Posterior
      approaches have also been used with success, but they require longer-length
      fusion. To obtain a stable fixation, the placement of instrumentation, in
      conjunction with judicious use of polymethylmethacrylate augmentation, is
      crucial. Preoperative embolization should be considered in patients with
      extremely vascular tumors such as renal cell carcinoma. Vertebroplasty, a newly
      described procedure in which the metastatic spinal lesions are treated via a
      percutaneous approach, may be indicated in selected cases of intractable pain
      caused by non- or minimally fractured vertebrae.

PMID- 16463993
TI  - Evaluation and treatment of spinal metastases: an overview.
AB  - Metastases to the spine are a common and somber manifestation of systemic
      neoplasia. The incidence of spinal metastases continues to increase, likely a
      result of increasing survival times for patients with cancer. Historically,
      surgery for spinal metastases has consisted of simple decompressive laminectomy.
      Results obtained in retrospective case series, however, have shown that this
      treatment provides little benefit to the patient. With the advent of better
      patient-related selection practices, in conjunction with new surgical techniques
      and improved postoperative care, the ability of surgical therapy to play an
      important and beneficial role in the multidisciplinary care of cancer patients
      with spinal disease has improved significantly. Controversy remains, however,
      with respect to the relative merits of surgery, radiotherapy, chemotherapy, or a
      combination of these treatments. In this topic review, the literature on spinal
      column and spinal cord metastases is collated to provide a description of the
      presentation, investigations, indications for surgical therapy, and the role of
      adjuvant cancer therapies for patients with spinal metastases. In addition, the
      authors discuss the different surgical strategies available in the armamentarium
      of the neurosurgeon treating patients with spinal metastasis.

PMID- 16463994
TI  - Management of metastatic tumors of the spine: strategies and operative
      indications.
AB  - The spinal column is the most frequent site of bone metastasis in the body. Spine
      surgeons are often involved in the care of these patients only after nonoperative
      management has failed. Because surgery has been viewed as no better than
      radiotherapy in the treatment of metastasis of the spine, it has only been used
      as a salvage approach. These views are based on a body of literature in which
      laminectomy combined with radiotherapy was compared with radiotherapy alone.
      Anterior approaches to the spine are now popular and familiar to most surgeons.
      These approaches allow direct access to the metastatic lesion, reconstruction of
      the anterior vertebral column, and the placement of anterior instrumentation.
      Outcomes are frequently much better when this combined treatment is used instead
      of radiotherapy alone. In selected patients, surgery may be desired as first-line
      therapy before radio- or chemotherapy has been initiated. The controversy
      surrounding surgery for metastatic spinal disease is reviewed. Treatment
      strategies, both operative and nonoperative, are presented. Indications and
      strategies for surgery are also presented, and the supporting literature is
      reviewed.

PMID- 16463995
TI  - Medical management and adjuvant therapies in spinal metastatic disease.
AB  - Metastatic spinal tumors are an increasingly common and difficult problem
      encountered by neurosurgeons and orthopedic surgeons. To improve therapies and
      increase life expectancy for patients with tumors such as those of the breast and
      prostate, a global, systematic approach is required to maximize the preservation
      of neurological function, maintenance of spinal stability, and relief of pain,
      all with the ultimate goal of improved functional capacity and quality of life
      (QOL). Although radiotherapy and surgery are still the primary therapeutic
      options, several new adjuvant therapies initially implemented to control pain
      more effectively have also been shown to reduce overall skeleton-related
      complications (pathological fractures and hypercalcemia) and may ultimately
      improve and extend QOL. This more global approach to spinal metastases also
      includes optimizing each patient's overall medical condition and potential for
      healing (that is, nutrition), as well as avoiding potential complications
      associated with metastatic disease (such as deep vein thrombosis), including
      excessive blood loss in the case of renal metastasis. A thorough knowledge and
      understanding of these therapeutic adjuvants is required to optimize care and to
      respond to our increasingly medically knowledgable patient population whose
      access to prevalent medical information has been increased because of the
      internet.

PMID- 16463996
TI  - Perioperative complications with costotransversectomy and anterior approaches to
      thoracic and thoracolumbar tumors.
AB  - OBJECT: Anterior decompression and stabilization for thoracic spinal tumors often
      involves a thoracotomy and can be associated with surgical approach-related
      complications. An alternative to thoracotomy is surgery via a
      costotransversectomy exposure. To delineate the risks of surgery, the authors
      reviewed their prospective database for patients who had undergone surgery via
      either of these approaches for thoracic or thoracolumbar tumors. The
      complications were recorded and graded based on severity and risk of impact on
      patient outcome. METHODS: Between September 1995 and April 2001, the authors
      performed 29 costotransversectomies (Group 1) and 18 thoracolumbar or combined
      (Group 2) approaches as initial operations for thoracic neoplasms. The age, sex,
      preoperative motor score, and preoperative Frankel grade did not significantly
      differ between the groups. In the costotransversectomy group there were greater
      numbers of metastases, upper thoracic procedures, and affected vertebral levels;
      additionally, the comorbidity rate based on Charlson score, was higher. The mean
      Frankel grades at discharge were not significantly different whereas the
      discharge motor and last follow-up motor scores were better in Group 2. There
      were 11 Group 1 and seven Group 2 patients who suffered at least one
      complication. The number or patients with complications, the mean number of
      complications, and severity of complications did not differ between the groups.
      CONCLUSIONS: Compared with anterior or combined approaches, the incidence and
      severity of perioperative complications in the surgical treatment of thoracic and
      thoracolumbar spinal tumors is similar in patients who undergo
      costotransversectomy. Costotransversectomy may be the preferred operation in
      patients with significant medical comorbidity or tumors involving more than one
      thoracic vertebra.

PMID- 16463997
TI  - Image-guided spinal navigation: application to spinal metastases.
AB  - Image-guided spinal navigation is an adjuvant surgical technology that has
      evolved over the past decade. It has been used as a replacement for conventional
      intraoperative imaging techniques to improve the spine surgeon's spatial
      orientation to nonvisualized anatomy. The author will review the principles of
      image-guided technology in spinal surgery and focus on its application to the
      management of spinal metastatic disease.

PMID- 16463998
TI  - Image-guided radiosurgery in the treatment of spinal metastases.
AB  - OBJECT: The authors describe a new method for treating metastatic spinal tumors
      in which noninvasive, image-guided, frameless stereotactic radiosurgery is
      performed. Stereotactic radiosurgery delivers a high dose of radiation in a
      single or limited number of fractions to a lesion while maintaining delivery of a
      low dose to adjacent normal structures. METHODS: Image-guided radiosurgery was
      developed by coupling an orthogonal pair of real-time x-ray cameras to a
      dynamically manipulated robot-mounted linear accelerator that guides the
      radiation beam to treatment sites associated with radiographic landmarks. This
      procedure can be conducted in an outpatient setting without the use of framebased
      skeletal fixation. The system relies on skeletal landmarks or implanted fiducial
      markers to locate treatment targets. Four patients with spinal metastases
      underwent radiosurgery with total prescription doses of 1000 to 1600 cGy in one
      or two fractions. Alignment of the treatment dose with the target volume was
      accurate to within 1.5 mm. During the course of each treatment fraction, patient
      movement was less than 0.5 mm on average. Dosimetry was highly conformal, with a
      demonstrated ability to deliver 1600 cGy to the perimeter of an irregular target
      volume while keeping exposure to the cord itself below 800 cGy. CONCLUSIONS:
      These experiences indicate that frameless radiosurgery is a viable therapeutic
      option for metastatic spine disease.

PMID- 16463999
TI  - Stereotactic intensity-modulation radiation therapy for vertebral body and
      paraspinal tumors.
AB  - Therapeutic doses of radiation for paraspinal tumors are often limited by the
      dose-related tolerance of the spinal cord. Intensity-modulated radiation therapy
      (IMRT) is an advanced form of three-dimensional conformal radiation therapy that
      provides improved coverage of tumor volumes while reducing the radiation dose to
      the spinal cord. Computer-controlled multileaf collimation provides high
      conformality, which makes it feasible to treat tumors of any shape, even those
      that are wrapped around the spinal cord. The use of a newly developed,
      noninvasive body frame, the capability of fusing computerized tomography and
      magnetic resonance images, and on-line portal films provide precise target
      immobilization and target identification. In this paper the authors discuss their
      preliminary experience in six cases in which IMRT was used to treat paraspinal
      lesions in patients who harbored locally recurrent tumors and/or tumors that
      previously received the maximum doses of radiation that could be tolerated by the
      spinal cord.

PMID- 16464001
TI  - The role of vertebroplasty in metastatic spinal disease.
AB  - Many advances have been made in the treatment of metastatic spinal disease over
      the last few decades. Radiotherapy offers benefit and pain relief to many
      patients; however, this modality provides minimal vertebral stabilization.
      Surgical management consists of decompression and complex fusions. Vertebroplasty
      offers an adjuvant therapy to both radiotherapy and surgery by providing
      additional stabilization and pain relief. The results of case studies suggest
      that including vertebroplasty in the management of these patients is beneficial.
      In this article the authors review the role of vertebroplasty in metastatic
      spinal disease.

PMID- 16464000
TI  - Ultrasonographic guidance for spinal extracranial radiosurgery: technique and
      application for metastatic spinal lesions.
AB  - OBJECT: The relatively stationary anatomy of the intracranial compartment has
      allowed the development of stereotactic radiosurgery as an effective treatment
      option for many intracranial lesions. Difficulty in accurately tracking
      extracranial targets has limited its development in the treatment of these
      lesions. The ability to track extracranial structures in real time with
      ultrasound images allows a system to upgrade and interface pretreatment
      volumetric images for extracranial applications. In this report the authors
      describe this technique as applied to the treatment of localized metastatic
      spinal disease. METHODS: The extracranial stereotactic system consists of an
      optically tracked ultrasonography unit that can be registered to a linear
      accelerator coordinate system. Stereotactic ultrasound images are acquired
      following patient positioning, based on a pretreatment computerized tomography
      (CT) simulation. The soft-tissue shifts between the virtual CT-based treatment
      plan and the actual treatment are determined. The degree of patient offset is
      tracked and used to correct the treatment plan. The ultrasonography-based
      stereotactic navigation system is accurate to within an approximate means of 1.5
      mm based on testing with an absolute coordinate phantom. A radiosurgical
      treatment was delivered using the system for localization of a metastatic spinal
      lesion. Compared with the virtual CT simulation, the actual treatment plan
      isocenter was shifted 12.2 mm based on the stereotactic ultrasound image. The
      patient was treated using noncoplanar beams to a dose of 15.0 Gy to the 80%
      isodose shell in a single fraction. CONCLUSIONS: A system for high-precision
      radiosurgical treatment of metastatic spinal tumors has been developed, tested,
      and applied clinically. Optical tracking of the ultrasonography probe provides
      real-time tracking of the patient anatomy and allows computation of the target
      displacement prior to treatment delivery. The results reported here suggest the
      feasibility and safety of the technique.

PMID- 16464004
TI  - Prokaryotic nucleotide excision repair: the UvrABC system.

PMID- 16464003
TI  - Direct reversal of DNA alkylation damage.

PMID- 16464005
TI  - Molecular mechanisms of mammalian global genome nucleotide excision repair.

PMID- 16464007
TI  - DNA mismatch repair: functions and mechanisms.

PMID- 16464008
TI  - Mechanisms of maintaining genetic stability by homologous recombination.

PMID- 16464009
TI  - Mechanistic comparison of high-fidelity and error-prone DNA polymerases and
      ligases involved in DNA repair.

PMID- 16464010
TI  - Structure and mechanism of DNA polymerase Beta.

PMID- 16464006
TI  - Formation and repair of interstrand cross-links in DNA.

PMID- 16464011
TI  - DNA polymerase gamma in mitochondrial DNA replication and repair.

PMID- 16464012
TI  - Roles of DNA polymerase V and RecA protein in SOS damage-induced mutation.

PMID- 16464013
TI  - Interactions of carcinogen-bound DNA with individual DNA polymerases.

PMID- 16464014
TI  - Lagging strand replication proteins in genome stability and DNA repair.

PMID- 16464015
TI  - RNA polymerase encounters with DNA damage: transcription-coupled repair or
      transcriptional mutagenesis?

PMID- 16464016
TI  - Computational approaches for investigating base flipping in oligonucleotides.

PMID- 16464017
TI  - Toward a detailed understanding of base excision repair enzymes: transition state
      and mechanistic analyses of N-glycoside hydrolysis and N-glycoside transfer.

PMID- 16464018
TI  - Thermodynamic and kinetic methods of analyses of protein-nucleic acid
      interactions. From simpler to more complex systems.

PMID- 16464019
TI  - NMR structures of damaged DNA.

PMID- 16464020
TI  - DNA ligases: structure, reaction mechanism, and function.

PMID- 16464022
TI  - Catalytic promiscuity and the divergent evolution of DNA repair enzymes.

PMID- 16464023
TI  - DNA repair in plants.

PMID- 16464021
TI  - Evaluation of molecular models for the affinity maturation of antibodies: roles
      of cytosine deamination by AID and DNA repair.

PMID- 16464024
TI  - Ru(II)-based metallosurfactant forming inverted aggregates.
AB  - Knowing the advantages of incorporating a transition metal into interfaces, we
      report on the first inverted aggregates formed using metallosurfactants. The
      metallosurfactant possesses four long linear tails that account for the shielding
      of the polar headgroup in apolar solvents. The nature of the so-formed aggregates
      changes dramatically from inverted vesicles (toluene) to inverted micelles
      (hexane). The size of the aggregates was determined using dynamic light
      scattering. Atomic force microscopy allowed us to study the dry structure of the
      vesicles on a glass surface.

PMID- 16464025
TI  - Conversion between hexagonal GaN and beta-Ga(2)O(3) nanowires and their
      electrical transport properties.
AB  - We have observed that the hexagonal GaN nanowires grown from a simple chemical
      vapor deposition method using gallium metal and ammonia gas are usually gallium
      doped. By annealing in air, the gallium-doped hexagonal GaN nanowires could be
      completely converted to beta-Ga(2)O(3) nanowires. Annealing the beta-Ga(2)O(3)
      nanowires in ammonia could convert them back to undoped hexagonal GaN nanowires.
      Field effect transistors based on these three kinds of nanowires were fabricated,
      and their performances were studied. Because of gallium doping, the as-grown GaN
      nanowires show a weak gating effect. Through the conversion process of GaN
      nanowires (gallium-doped) --> Ga(2)O(3) nanowires --> GaN nanowires (undoped) via
      annealing, the final undoped GaN nanowires display different electrical
      properties than the initial gallium-doped GaN nanowires, show a pronounced n-type
      gating effect, and can be completely turned off.

PMID- 16464026
TI  - Diameter-dependent electromechanical properties of GaN nanowires.
AB  - The diameter-dependent Young's modulus, E, and quality factor, Q, of GaN
      nanowires were measured using electromechanical resonance analysis in a
      transmission electron microscope. E is close to the theoretical bulk value (
      approximately 300 GPa) for a large diameter nanowire (d=84 nm) but is
      significantly smaller for smaller diameters. At room temperature, Q is as high as
      2,800 for d=84 nm, significantly greater than what is obtained from micromachined
      Si resonators of comparable surface-to-volume ratio. This implies significant
      advantages of smooth-surfaced GaN nanowire resonators for nanoelectromechanical
      system (NEMS) applications. Two closely spaced resonances are observed and
      attributed to the low-symmetry triangular cross section of the nanowires.

PMID- 16464027
TI  - Sequence-independent helical wrapping of single-walled carbon nanotubes by long
      genomic DNA.
AB  - Because of their nanometer sizes and molecular recognition capabilities,
      biological systems have garnered much attention as vehicles for the directed
      assembly of nanoscale materials.(1-6) One of the greatest challenges of this
      research has been to successfully interface biological systems with electronic
      materials, such as semiconductors and metals. As a means to address some of these
      issues, Sarikaya, Belcher, and others have used a combinatorial technique called
      phage display(7-9) to discover new families of peptides that showed binding
      affinities to various substrates. More recently, Zheng and co-workers used
      combinatorial DNA libraries to isolate short DNA oligomers (30-90 bases) that
      could disperse single-walled carbon nanotubes (SWCNT) in water.(10) Through a
      systematic analysis, they found that short oligonucleotides having repeating
      sequences of gunanines and thymines (dGdT)(n) could wrap in a helical manner
      around a CNT with periodic pitch.(11) Although helix formation around SWCNTs
      having regular pitches is an effective method for dispersing and separating CNTs,
      the need for specific repeating sequences limits use to non-natural DNA that must
      be synthesized with optimal lengths of less than 150 bases. In contrast, we
      demonstrate here that long genomic single-stranded DNA (>>100 bases) of a
      completely random sequence of bases can be used to disperse CNTs efficiently
      through the single-stranded DNA's (ssDNA) ability to form tight helices around
      the CNTs with distinct periodic pitches. Although this process occurs
      irrespective of the DNA sequence, we show that this process is highly dependent
      on the removal of complementary strands. We also demonstrate that although the
      helix pitch-to-pitch distances remain constant down the length of a single CNT,
      the distances are variable from one DNA-CNT to another. Finally, we report
      initial work that shows that methods developed to align long dsDNA can be applied
      in a similar fashion to produce highly dense arrays of aligned ssDNA-CNT hybrids.

PMID- 16464028
TI  - Vibrational excitations in single trimetal-molecule transistors.
AB  - Single-molecule transistors incorporating trimetal molecules of
      Cu(3)(dpa)(4)Cl(2) and Ni(3)(dpa)(4)Cl(2) (dpa = 2,2'-dipyridylamide) have been
      fabricated. Conductance is measured as a function of bias and gate voltages at
      low temperature, showing single-electron tunneling behavior through the
      molecules. Additional structures corresponding to the excitations in the
      molecules are observed, which can be attributed to intramolecular vibrational
      excitations coupled to the electron tunneling processes. The energies of the
      vibrational states are dependent on the redox state of the included molecules.

PMID- 16464029
TI  - In vivo and scanning electron microscopy imaging of up-converting nanophosphors
      in Caenorhabditis elegans.
AB  - We show here that upconversion phosphors can be imaged both by infrared
      excitation and in a scanning electron microscope. We have synthesized and
      characterized for this work up-converting phosphor nanoparticles nonaggregated
      nanocrystals of size range 50-200 nm. We have investigated the optical properties
      of 50-200 nm nanoparticles and found a square dependence of the emitted visible
      fluorescence on the infrared excitation and verified that under electron
      excitation similar narrow band emission spectra can be obtained as is seen with
      IR upconversion. The viability of the nanoparticles for biological imaging was
      confirmed by imaging the digestive system of the nematode worm Caenorhabditis
      elegans, and we have confirmed using energy-dispersive X-ray analysis that the up
      conversion nanoparticles can be identified in a scanning electron microscope at
      high spatial resolution.

PMID- 16464031
TI  - Three-dimensional nanoscale composition mapping of semiconductor nanowires.
AB  - We demonstrate the three-dimensional composition mapping of a semiconductor
      nanowire with single-atom sensitivity and subnanometer spatial resolution using
      atom probe tomography. A new class of atom probe, the local electrode atom probe
      (LEAP) microscope, was used to map the position of single Au atoms in an InAs
      nanowire and to image the interface between a Au catalyst and InAs in three
      dimensions with 0.3-nm resolution. These results establish atom probe tomography
      as a uniquely powerful tool for analyzing the chemical composition of
      semiconductor nanostructures.

PMID- 16464030
TI  - Raman microprobe analysis of elastic strain and fracture in electrophoretically
      deposited CdSe nanocrystal films.
AB  - The mechanical stability of nanocrystal films is critical for applications, yet
      largely unexplored. Raman microprobe analysis used here to probe the nanocrystal
      cores of thick, fractured electrophoretically deposited films of 3.2 nm diameter
      CdSe nanocrystals measures approximately 2.5% in-plane tensile strain in cores of
      unfractured films. The crack dimensions determine the overall in-plane film
      strain, approximately 11.7%, and the film biaxial modulus, approximately 13.8
      GPa, from which the biaxial modulus of the trioctylphosphine oxide ligand matrix
      is inferred, approximately 5.1 GPa.

PMID- 16464032
TI  - A new method to synthesize complicated multi-branched carbon nanotubes with
      controlled architecture and composition.
AB  - Here we develop a simple method by using flow fluctuation to synthesize arrays of
      multi-branched carbon nanotubes (CNTs) that are far more complex than those
      previously reported. The architectures and compositions can be well controlled,
      thus avoiding any template or additive. A branching mechanism of fluctuation
      promoted coalescence of catalyst particles is proposed. This finding will provide
      a hopeful approach to the goal of CNT-based integrated circuits and be valuable
      for applying branched junctions in nanoelectronics and producing branched
      junctions of other materials.

PMID- 16464033
TI  - Microsphere templating as means of enhancing surface activity and gas sensitivity
      of CaCu(3)Ti(4)O(12) thin films.
AB  - Chemical and physical synthesis routes were combined to prepare macroporous
      CaCu(3)Ti(4)O(12) thin films by pulsed laser deposition onto poly(methyl
      methacrylate) (PMMA) microsphere templated substrates. These films showed
      remarkably enhanced gas sensitivity compared with control films deposited on
      untreated substrates, demonstrating the virtues of combining thin film physical
      vapor deposition (PVD) techniques in concert with colloidal templates to produce
      macroporous structures of inorganic films with enhanced surface activity for
      applications in chemical sensors, catalysts, and fuel cells.

PMID- 16464034
TI  - Self-assembly and characterization of layered double hydroxide/DNA hybrids.
AB  - The purpose of this study was to control the fabrication of new labile
      supramolecular assemblies by formulating associations of DNA molecules with
      inorganic layered double hydroxides (LDHs). The results show that LDH/DNA hybrids
      synthesized by a coprecipitation route involving the in situ formation of LDHs
      around DNA molecules acting as templates were characterized by a lamellar
      organization, with DNA molecules sandwiched between hydroxide layers, exhibiting
      a regular spacing of 1.96 nm. Our results indicate that labile complexes
      resulting from the association of nucleic acids and inorganic materials can be
      obtained not only by anion exchange but also by a direct self-assembly route.

PMID- 16464035
TI  - Mobility in semiconducting carbon nanotubes at finite carrier density.
AB  - Carbon nanotube field-effect transistors operate over a wide range of electron or
      hole density, controlled by the gate voltage. Here we calculate the mobility in
      semiconducting nanotubes as a function of carrier density and electric field, for
      different tube diameters and temperatures. The low-field mobility is a
      nonmonotonic function of carrier density and varies by as much as a factor of 4
      at room temperature. At low density, with increasing field the drift velocity
      reaches a maximum and then exhibits negative differential mobility, due to the
      non-parabolicity of the band structure. At a critical density, rho(c)
      approximately 0.35-0.5 electrons/nm, the drift velocity saturates at around one
      third of the Fermi velocity. Above rho(c), the velocity increases with field
      strength with no apparent saturation.

PMID- 16464036
TI  - Controlling enzymatic reactions by geometry in a biomimetic nanoscale network.
AB  - We demonstrate that a transition from a compact geometry (sphere) to a structured
      geometry (several spheres connected by nanoconduits) in nanotube-vesicle networks
      (NVNs) induces an ordinary enzyme-catalyzed reaction to display wavelike
      properties. The reaction dynamics can be controlled directly by the geometry of
      the network, and such networks can be used to generate wavelike patterns in
      product formation. The results have bearing for understanding catalytic reactions
      in biological systems as well as for designing emerging wet chemical
      nanotechnological devices.

PMID- 16464037
TI  - Use of highly-ordered TiO(2) nanotube arrays in dye-sensitized solar cells.
AB  - We describe the use of highly ordered transparent TiO(2) nanotube arrays in dye
      sensitized solar cells (DSCs). Highly ordered nanotube arrays of 46-nm pore
      diameter, 17-nm wall thickness, and 360-nm length were grown perpendicular to a
      fluorine-doped tin oxide-coated glass substrate by anodic oxidation of a titanium
      thin film. After crystallization by an oxygen anneal, the nanotube arrays are
      treated with TiCl(4) to enhance the photogenerated current and then integrated
      into the DSC structure using a commercially available ruthenium-based dye.
      Although the negative electrode is only 360-nm-thick, under AM 1.5 illumination
      the generated photocurrent is 7.87 mA/cm(2), with a photocurrent efficiency of
      2.9%. Voltage-decay measurements indicate that the highly ordered TiO(2) nanotube
      arrays, in comparison to nanoparticulate systems, have superior electron
      lifetimes and provide excellent pathways for electron percolation. Our results
      indicate that remarkable photoconversion efficiencies may be obtained, possibly
      to the ideal limit of approximately 31% for a single photosystem scheme, with an
      increase of the nanotube-array length to several micrometers.

PMID- 16464038
TI  - Temperature-activated interfacial friction damping in carbon nanotube polymer
      composites.
AB  - Effect of temperature on interfacial sliding in single-walled carbon nanotube
      polycarbonate composites is investigated experimentally. We show that interfacial
      slip at the tube-polymer interfaces can be activated at relatively low dynamic
      strain levels ( approximately 0.35%) by raising temperature to approximately 90
      degrees C. We attribute this to increased mobility of the polymer chain backbones
      at elevated temperatures and thermal relaxation of the radial compressive
      stresses at the tube-polymer interfaces. These results show the potential of
      polymer nanocomposites as high-temperature damping materials for vibration and
      acoustic suppression in a variety of dynamic systems.

PMID- 16464039
TI  - Infrared imaging of the nanometer-thick accumulation layer in organic field
      effect transistors.
AB  - We report on infrared (IR) spectromicroscopy of the electronic excitations in
      nanometer-thick accumulation layers in field-effect transistor (FET) devices
      based on poly(3-hexylthiophene). IR data allows us to explore the charge
      injection landscape and uncovers the critical role of the gate insulator in
      defining relevant length scales. This work demonstrates the unique potential of
      IR spectroscopy for the investigation of physical phenomena at the nanoscale
      occurring at the semiconductor-insulator interface in FET devices.

PMID- 16464040
TI  - Infrared photodetectors in heterostructure nanowires.
AB  - We report on spectrally resolved photocurrent measurements on single self
      assembled nanowire heterostructures. The wires, typically 3 microm long with an
      average diameter of 85 nm, consist of InAs with a 1 microm central part of InAsP.
      Two different sets of wires were prepared with phosphorus contents of 15+/-3% and
      35+/-3%, respectively, as determined by energy-dispersive spectroscopy
      measurements made in transmission electron microscopy. Ohmic contacts are
      fabricated to the InAs ends of the wire using e-beam lithography. The conduction
      band offset between the InAs and InAsP regions virtually removes the dark current
      through the wires at low temperature. In the optical experiments, interband
      excitation in the phosphorus-rich part of the wires results in a photocurrent
      with threshold energies of about 0.65 and 0.82 eV, respectively, in qualitative
      agreement with the expected band gap of the two compositions. Furthermore, a
      strong polarization dependence is observed with an order of magnitude larger
      photocurrent for light polarized parallel to the wire than for light polarized
      perpendicular to the wire. We believe that these wires form promising candidates
      as nanoscale infrared polarization-sensitive photodetectors.

PMID- 16464041
TI  - Fabrication of single-walled carbon-nanotube-based pressure sensors.
AB  - We report on the fabrication and characterization of bulk micromachined pressure
      sensors based on individual single-walled carbon nanotubes (SWNTs) as the active
      electromechanical transducer elements. The electromechanical sensor device
      consists of an individual electrically connected SWNT adsorbed on top of a 100-nm
      thick atomic layer deposited (ALD) circular alumina (Al(2)O(3)) membrane with a
      radius in the range of 50-100 microm. A white light interferometer (WLI) was used
      to measure the deflection of the membrane due to differential pressure, and the
      mechanical properties of the device were characterized by bulge testing. Finally,
      we performed the first electromechanical measurements on strained metallic SWNTs
      adhering to a membrane and found a piezoresistive gauge factor of approximately
      210 for metallic SWNTs.

PMID- 16464042
TI  - Quantifying electrochemical nucleation and growth of nanoscale clusters using
      real-time kinetic data.
AB  - Electrochemical techniques are used widely for the fabrication of nanostructured
      materials, yet a quantitative understanding of nucleation and growth remains
      elusive. Here we probe electrochemical nucleation and growth of individual
      nanoclusters in real time by combining current-time measurements with
      simultaneous video imaging. We show discrepancies between the growth kinetics
      measured for individual nanoclusters and the predictions of models, and we
      describe a significant revision to conventional models that can explain the
      results. This improved understanding of nucleation and growth allows a more
      quantitative approach to the electrochemical fabrication of nanoscale structures.

PMID- 16464043
TI  - Well-aligned open-ended carbon nanotube architectures: an approach for device
      assembly.
AB  - To circumvent the high carbon nanotube (CNT) growth temperature and poor adhesion
      with the substrates that currently plague CNT implementation, we proposed using
      CNT transfer technology enabled by open-ended CNTs. The process is featured with
      separation of CNT growth and CNT device assembly. Field emission testing of the
      as-assembled CNT devices is in good agreement with the Fowler-Nordheim (FN)
      equation, with a field enhancement factor of 4,540. This novel technique shows
      promising applications for positioning CNTs on temperature-sensitive substrates
      and for the fabrication of field emitters, electrical interconnects, and thermal
      management structures in microelectronics packaging.

PMID- 16464044
TI  - Periodic square-like gold nanoparticle arrays templated by self-assembled 2D DNA
      Nanogrids on a surface.
AB  - We report the use of a self-assembled two-dimensional (2D) DNA nanogrid as a
      template to organize 5-nm gold nanoparticles (Au NPs) into periodic square
      lattices. Each particle sits on only a single DNA tile. The center-to-center
      interparticle spacing between neighboring particles is controlled to be
      approximately 38 nm. These evenly distributed Au NP arrangements with accurate
      control of interparticle spacing may find applications in nanoelectronic and
      nanophotonic devices.

PMID- 16464045
TI  - Nanoscale pipetting for controlled chemistry in small arrayed water droplets
      using a double-barrel pipet.
AB  - We present a new methodology which provides for the miniaturization of one of the
      most common tools in use in chemistry and biology laboratories today-the
      micropipet. We have used glass-fabricated double-barrel nanopipets to
      controllably produce arrayed water droplets with volumes as small as a few
      attoliters under an organic layer. We have addressed individual droplets and
      added controlled amounts of either additional volume or reagents from one of the
      barrels of the pipet. We demonstrate that this method can be used for
      miniaturized cell-free protein expression.

PMID- 16464047
TI  - ZnO nanobelt/nanowire Schottky diodes formed by dielectrophoresis alignment
      across au electrodes.
AB  - Rectifying diodes of single nanobelt/nanowire-based devices have been fabricated
      by aligning single ZnO nanobelts/nanowires across paired Au electrodes using
      dielectrophoresis. A current of 0.5 microA at 1.5 V forward bias has been
      received, and the diode can bear an applied voltage of up to 10 V. The ideality
      factor of the diode is approximately 3, and the on-to-off current ratio is as
      high as 2,000. The detailed IV characteristics of the Schottky diodes have been
      investigated at low temperatures. The formation of the Schottky diodes is
      suggested due to the asymmetric contacts formed in the dielectrophoresis aligning
      process.

PMID- 16464046
TI  - Inelastic transport through molecules: comparing first-principles calculations to
      experiments.
AB  - We present calculations of the elastic and inelastic conductance through three
      different hydrocarbon molecules connected to gold electrodes. Our method is based
      on a combination of the nonequilibrium Green's function method with density
      functional theory. Vibrational effects in these molecular junctions were
      previously investigated experimentally by Kushmerick et al. (Nano Lett. 2004, 4,
      639). Our results are in good agreement with the measurements and provide
      insights into (i) which vibrational modes are responsible for inelastic
      scattering, (ii) the width of the inelastic electron tunneling signals, and (iii)
      the mechanisms of heating and cooling of the vibrational modes induced by the
      coupling to the charge carriers.

PMID- 16464048
TI  - Tuning surface energies with nanopatterned substrates.
AB  - A novel approach to varying the surface energy of biofunctional substrates has
      been developed, where surface energies are controlled by utilizing tunable
      nanopatterned substrates. In this study we functionalized the nanopattern with
      streptavidin, providing an adhesive interface for biotinylated probes. To obtain
      the surface energies, we applied the Johnson-Kendall-Roberts model to the
      adhesion-induced deformation of elastic beads. The results reveal a linear
      relationship between surface energy and ligand density, demonstrating the
      capability of this technique to adjust surface energy.

PMID- 16464049
TI  - Patterning lines by capillary flows.
AB  - We report that capillary flows in an evaporating thin film create line patterns,
      with widths ranging from a few micrometers to less than 100 nm. Deliberate
      patterning of such lines requires contact-line pinning and the presence of
      foaming surfactants. Large-scale photolithography can guide and control these
      structures by creating pinning points and steering evaporation. We provide
      demonstrations of this process by making self-assembling lines of colloidal
      quantum dots and microspheres.

PMID- 16464050
TI  - Magic structures of h-passivated 110 silicon nanowires.
AB  - We report a genetic algorithm approach combined with ab initio calculations to
      determine the structure of hydrogenated 110 Si nanowires. As the number of atoms
      per length increases, we find that the cross section of the nanowire evolves from
      chains of six-atom rings to fused pairs of such chains to hexagons bounded by
      {001} and {111} facets. Our calculations predict that hexagonal wires become
      stable starting at about 1.2 nm diameter, which is consistent with recent
      experimental reports of nanowires with diameters of about 3 nm.

PMID- 16464051
TI  - Reversible stimuli-responsive nanostructures assembled from amphiphilic block
      copolymers.
AB  - We present a novel route to assemble perpendicular cylinders by converting an
      asymmetric diblock copolymer from poly(styrene-b-tert-butyl acrylate) (PS-b-PtBA)
      to poly(styrene-b-acrylic acid) (PS-b-PAA) using an autocatalytic reaction. Upon
      exposure of the films of PS-b-PAA to water, PAA cylinders constrained by the
      continuous, glassy PS phase protrude 10 nm above the surface and swell laterally
      to form mushroom caps, rendering the entire surface hydrophilic. Upon annealing,
      the original nanostructures re-form demonstrating reversibility of swelling.
      Because of their stimuli-responsive behavior, these nanoscale materials are
      excellent candidates for sensors and microfluidic applications.

PMID- 16464052
TI  - Template synthesis of arrays of nano fuel cells.
AB  - A method for the construction of an array of fuel cells wherein each cell is 200
      nm in diameter is presented. Electrodeposition of Pt-Cu nanowires inside the
      cylindrical pores of an Anodisc filter membrane and the subsequent dealloying of
      the Cu by soaking the filter in fuming nitric acid for several hours are used to
      construct an array of porous platinum electrodes. About 10(9) electrically
      isolated cylindrical porous electrodes, each 200 nm in diameter, are formed in
      this manner. Utilizing two arrays of porous electrodes with a polymer electrolyte
      membrane or an electrolyte support matrix sandwiched between, an array of nano
      fuel cells is produced. This method of producing an array of coplanar fuel cells
      allows for the series connection of fuel cells outside the array and eliminates
      the need for fuel and air manifolds, greatly reducing the overall system
      complexity. Initial prototypes utilizing an aqueous solution of NaBH(4) as a fuel
      have produced power densities of ca. 1 mW/cm(2) based on an estimate of the area
      of the current collectors in contact with the nano-fuel-cell array and have
      demonstrated the ability to wire bundles of fuel cells either in parallel or in
      series.

PMID- 16464053
TI  - Controlling nanowear in a polymer by confining segmental relaxation.
AB  - Molecular relaxation of a copolymer designed for nano-electromechanical systems
      was chemically confined by varying the spacing between cross-links, delta(c). A
      critical cross-link spacing of 1-3 nm marks a transition in the nano-mechanical
      properties evaluated by atomic force microscopy. The transition reveals an
      interplay between the cross-link spacing and the length scale for backbone
      relaxation, xi(alpha), in cooperatively rearranging regions. For delta(c) >>
      xi(alpha), the natural backbone relaxation process is relatively unaffected by
      the cross-links and a ductile, low hardness behavior results. For delta(c) <
      xi(alpha), the cross-links directly interfere with backbone relaxation and
      confine segmental mobility, leading to a brittle, high hardness response.

PMID- 16464054
TI  - Long-lived charged states in single-walled carbon nanotubes.
AB  - We present continuous wave photoinduced absorption spectroscopy of single-walled
      carbon nanotubes dispersed in a polymer matrix. The spectrum is dominated by a
      modulation of the absorption line shape, predominantly of large diameter tubes,
      that we assigned to electroabsorption caused by local electric fields arising
      from trapped photoinduced charges. The lack of selectivity in the excitation
      points to an efficient migration of the photoexcited states, either the singlet
      excitons or the charges resulting from their dissociation.

PMID- 16464055
TI  - Proteolytic surface functionalization enhances in vitro magnetic nanoparticle
      mobility through extracellular matrix.
AB  - Steric barriers such as collagen I sharply limit interstitial delivery of
      macromolecular and nanoparticle (NP) based therapeutic agents. Collagenase-linked
      superparamagnetic NPs overcame these barriers and moved through in vitro
      extracellular matrix (ECM) at 90 microm h(-1), a rate similar to invasive cells,
      under the influence of a magnetic field. NP migration in ECM diminished linearly
      over 5 days. The collagenase-NP construct overcame two of the most significant
      barriers to nano- and microscale therapeutics deployment: proteolytic enzyme
      stability was maintained during a clinically useful time frame by immobilization
      on the NP surface and degradation of interstitial barriers to tissue
      biodistribution was enabled by the conjugated microbial protease.

PMID- 16464056
TI  - Structure of semidilute single-wall carbon nanotube suspensions and gels.
AB  - The microscopic network structure of surfactant-stabilized single-wall carbon
      nanotubes (SWNTs) in water was investigated as a function of SWNT concentration
      in the semidilute (overlapping) regime using small-angle neutron scattering
      (SANS). Most of the samples exhibit rigid rod behavior (i.e., Q(-1) intensity
      variation) at large scattering wavevector, Q, and a crossover to network behavior
      (i.e., approximately Q(-2) intensity variation) at low Q. The mesh size, xi, of
      the network was determined from the crossover of rigid rod to network behavior in
      the SANS intensity profile and was found to decrease with increasing SWNT
      concentration. When the dispersion quality of these associating rigid rods was
      degraded, only approximately Q(-2) intensity variation was observed at both high
      and low Q. Small-angle X-ray scattering measurements of the same stable
      dispersions were relatively insensitive to network structure because of poor
      contrast between SWNTs and surfactant.

PMID- 16464057
TI  - Germanium nanowire epitaxy: shape and orientation control.
AB  - Epitaxial growth of nanowires along the 111 directions was obtained on Ge(111),
      Ge(110), Ge(001), and heteroepitaxial Ge on Si(001) substrates at temperatures of
      350 degrees C or less by gold-nanoparticle-catalyzed chemical vapor deposition.
      On Ge(111), the growth was mostly vertical. In addition to 111 growth, 110 growth
      was observed on Ge(001) and Ge(110) substrates. Tapering was avoided by the use
      of the two-temperature growth procedure, reported earlier by Greytak et al.

PMID- 16464058
TI  - Multi-branching carbon nanotubes via self-seeded catalysts.
AB  - A novel multi-branching carbon nanotube (CNT) structure is synthesized by direct
      current plasma enhanced chemical vapor deposition. The structure consists of
      aligned CNTs which have branches of smaller diameters growing aligned along a
      direction perpendicular to the original CNT. The mechanism of branching is
      explained in terms of a self-seeding of Ni catalyst which is transferred by
      sputtering from the original catalyst particles in the backbone CNTs to the walls
      of those CNTs. It is also shown that the branching induced a large increase in
      surface area and total nanotube length and can be beneficial in supporting very
      fine Pt nanoparticles for fuel cell and other catalytic applications. Such an
      array of Y-junction nanostructures could be useful for the fabrication of a high
      density array of nanoelectronics switches and transistors.

PMID- 16464059
TI  - Measurement of wetting properties of individual boron nitride nanotubes with the
      wilhelmy method using a nanotube-based force sensor.
AB  - The wetting properties of individual boron nitride nanotubes (BNNTs) were studied
      with the Wilhelmy method in ambient conditions. A nanotube-based force sensor
      having a force resolution of 0.1 nN, calibrated with the wetting force method,
      was used to study the interactions between BNNTs and liquids in situ. The static
      contact angles of the liquids on BNNTs were evaluated, and the surface tension of
      the BNNT along with its surface tension components was determined based on the
      Owens and Wendt method and the van Oss-Chaudhury-Good acid-base theory.

PMID- 16464060
TI  - Impact of ripening on manganese-doped ZnSe nanocrystals.
AB  - We examine the impact of growth kinetics on the incorporation of Mn dopants into
      ZnSe nanocrystals. We synthesize such particles, also known as colloidal quantum
      dots, and use optical spectroscopy to extract information about the average
      number of Mn impurities per nanocrystal as the reaction proceeds. We find that
      this number increases with particle growth until the Zn and/or Se precursors are
      depleted in the reaction solution. If the reaction is continued further, then
      ripening of the colloid begins and the average number of Mn per nanocrystal
      decreases, even as the particles slowly increase in size. We show that this
      effect, which is detrimental for enhanced doping, can be avoided if the reactant
      concentration is maintained by addition of more reactants. We consider several
      explanations and conclude that intraparticle ripening, in which material is
      redistributed on the same nanocrystal due to evolution of the particle shape, is
      the most consistent with experimental observations.

PMID- 16464061
TI  - Broadband homonuclear correlation spectroscopy at high magnetic fields and MAS
      frequencies.
AB  - We present a new homonuclear recoupling sequence, CMAR, that allows observation
      of 2D 13C-13C correlation spectra at high magnetic fields and MAS frequencies (10
      30 kHz). The main advantages of the sequence are that it provides efficient,
      broadband dipolar recoupling and concurrently decouples the 1H spins from the
      13C's. Thus, no additional 1H decoupling is required during the mixing period,
      thereby significantly reducing the radio frequency power requirements for the
      experiment. Thus, CMAR significantly extends the range of applicability of the
      usual homonuclear recoupling techniques and should be of major interest for
      structure determinations of biomolecules at high magnetic fields.

PMID- 16464063
TI  - Enhanced CO tolerance for hydrogen activation in Au-Pt dendritic heteroaggregate
      nanostructures.
AB  - Au-Pt heteroaggregate nanostructures were prepared by sequential reduction
      methods. The structures have approximately 11 nm Au cores with Pt "tendrils"
      attached to the Au surface. The heteroaggregates are active H2 oxidation
      catalysts and show high activity at 90 degrees C in the presence of 1000 ppm CO.
      The surprising CO-tolerant behavior arises from the composition and unusual
      architecture of the particles.

PMID- 16464062
TI  - Characterization of nonbiological antimicrobial polymers in aqueous solution and
      at water-lipid interfaces from all-atom molecular dynamics.
AB  - We have applied molecular dynamics to investigate the structural properties and
      activity of recently synthesized amphiphilic polymethacrylate derivatives,
      designed to mimic the antimicrobial activity of natural peptides. The
      composition, molecular weight, and hydrophobicity (ratio of hydrophobic and
      cationic units) of these short copolymers can be modulated to achieve structural
      diversity, which is crucial in controlling the antimicrobial activity. We have
      carried out all-atom molecular dynamics to systematically investigate the
      conformations adopted by these copolymers in water and at the water-lipid
      interface as a function of sequence and the chemical nature of the monomers. For
      two sequences, we observe partial insertion into the bilayer. Formation of strong
      interactions between the lipid headgroups and the amine groups of the polymers
      assists in the initial association with the lipids. However, the primary driving
      force for the observed partial insertion appears to be the hydrophobic effect.
      Our results indicate sensitive dependence of the overall shape on the sequence,
      suggesting that experimentally observed changes in activity can be correlated
      with particular sequences, providing an avenue for rational design.

PMID- 16464064
TI  - Electron hopping in pi-stacked covalent and self-assembled perylene diimides
      observed by ENDOR spectroscopy.
AB  - We have carried out room-temperature, solution-phase electron paramagnetic
      resonance and electron-nuclear double resonance studies on a series of radical
      anions based upon perylene-3,4:9,10-bis(dicarboximide) (PDI). The following
      systems were studied: two PDI monomers, a covalent, cofacial dimer, and two
      covalent trefoil-PDI3 molecules, one of which self-assembles into pi-stacked
      dimers. Full sharing of the unpaired electron in the covalent and self-assembled
      dimers is revealed by a halving of the hyperfine coupling constants in these
      species, relative to those of the monomers. These results and the electronic
      absorption spectra show that electron hopping on a >107 Hz time scale occurs
      between a reduced and neutral chromophoric pair.

PMID- 16464065
TI  - Rotaxanes of cyclic peptides.
AB  - The synthesis of rotaxanes derived from the synthetic peptide macrocycles cyclo(l
      ProGly)4 and cyclo(l-ProGly)5 and diammonium threads is described. [2]Rotaxanes
      are formed in good yields (56-63%), despite the disruption of internal amide
      amide hydrogen bonding in the macrocycles.

PMID- 16464066
TI  - Single unit cell thick samaria nanowires and nanoplates.
AB  - We report on the synthesis of samaria nanowires and nanoplates with a thickness
      of 1.1 nm. The cross-section of the nanowires is a rectangular shape with
      dimensions of 1.1 nm x 2.2 nm, which corresponded to the size of two unit cells
      of samaria. Under optimized conditions, we were able to synthesize as much as 10
      g of the nanowires.

PMID- 16464067
TI  - Chemical complementarity in the contacts for nanoscale organic field-effect
      transistors.
AB  - This study describes the effect of covalent derivatization of source and drain
      electrodes with monolayers of organic semiconductors. These monolayers form a
      template on the metal surface and provide better electronic coupling between the
      electrode and the semiconductor. We see a large improvement in nanoscale (40-100
      nm) transistors only when the monolayer presents functionality that is
      complementary to the chemical and electronic structure of the molecular
      semiconductor.

PMID- 16464068
TI  - Valence tautomeric transitions with thermal hysteresis around room temperature
      and photoinduced effects observed in a cobalt-tetraoxolene complex.
AB  - A dinuclear complex, [(CoTPA)2(DHBQ)](PF6)3, has been successfully synthesized
      that exhibits a valence tautomeric transition with a distinct hysteresis effect
      (13 K) around room temperature and photoinduced valence tautomerism under low
      temperature.

PMID- 16464071
TI  - Selective functionalization of 3-D polymer microstructures.
AB  - We demonstrate the selective functionalization of 3-D polymer microstructures
      that were created using multiphoton absorption polymerization. By fabricating
      different portions of the structures with acrylic and methacrylic polymers, we
      are able to take advantage of the differential reactivities of these materials to
      perform functionalization chemistry on a single polymeric component. We
      demonstrate the selective deposition of metal to create structures, such as a
      functional microinductor. Our strategy is quite general and can be extended
      readily to the deposition of materials, such as metal oxides and biomolecules.

PMID- 16464069
TI  - Stereocontrolled synthesis of spiroketals via Ti(Oi-Pr)4-mediated kinetic
      spirocyclization of glycal epoxides with retention of configuration.
AB  - A Ti(Oi-Pr)4-mediated kinetic spiroketalization reaction has been developed for
      the stereocontrolled target- and diversity-oriented synthesis of spiroketals. In
      contrast to most existing methods for spiroketal synthesis, this reaction does
      not rely upon thermodynamic control over the stereochemical configuration at the
      anomeric carbon. Stereochemically diverse glycals are first alkylated at the C1
      position to introduce a hydroxyl-bearing side chain, then epoxidized
      stereoselectively. Treatment with Ti(Oi-Pr)4 leads to an unusual kinetic epoxide
      opening spirocyclization (spirocycloisomerization) with retention of
      configuration at the anomeric carbon. The reaction is proposed to proceed via a
      chelation-controlled mechanism and has been used to form five-, six-, and seven
      membered rings with stereochemically diverse substituents. This approach may also
      be useful for the related intermolecular beta-mannosidation reaction. This Ti(Oi
      Pr)4-mediated spirocyclization is stereochemically complementary to our
      previously reported MeOH-induced spirocyclization, which proceeds with inversion
      of configuration, and together, these reactions provide comprehensive access to
      systematically stereochemically diversified spiroketals.

PMID- 16464070
TI  - Selective functionalization of independently addressed microelectrodes by
      electrochemical activation and deactivation of a coupling catalyst.
AB  - We demonstrate selective functionalization of independently addressed
      microelectrodes by electrochemical activation and deactivation of a coupling
      catalyst. 1,2,3-Triazole formation between terminal acetylenes and organic azides
      is efficiently catalyzed by copper(I) complexes (a Sharpless "click" reaction),
      while the oxidized copper(II) complexes are inactive. By electrochemically
      activating or deactivating the catalyst by switching its redox state, we
      demonstrate control over triazole formation between surface-immobilized azides
      and ethynylferrocene. The reaction proceeds on the time scale of minutes using
      submicromolar concentration of reactants and catalyst, requires mild potentials
      for catalyst activation and deactivation, and works in aqueous and mixed aqueous
      organic solvents. By appropriate biasing of each electrode, we selectively modify
      one of two chemically identical 10-mum-wide electrodes separated by 10 mum in an
      interdigitated array. The ability to switch on or off the reaction by electrical
      addressing together with the chemoselectivity of this reaction makes Cu(I)
      catalyzed triazole formation an ideal method for the chemical modification of
      multielectrode arrays.

PMID- 16464072
TI  - Gold(I)-catalyzed intra- and intermolecular hydroamination of unactivated
      olefins.
AB  - Ph3PAuOTf catalyzes efficient intra- and intermolecular hydroamination of
      unactivated olefins with sulfonamides.

PMID- 16464073
TI  - Catalyzed CO oxidation at 70 K on an extended Au/Ni surface alloy.
AB  - A Au/Ni(111) surface alloy catalyzes the oxidation of CO at low temperature by at
      least three distinct mechanisms. At the lowest temperature of 70 K, molecularly
      adsorbed O2, spectroscopically characterized as peroxo or superoxo species bound
      at multiple sites with vibrational frequencies of 865 and 950 cm-1, is the
      reactant with CO. Between 105 and 125 K, CO2 production coincides with O2
      dissociation, suggesting a "hot atom" mechanism. Above 125 K, adsorbed CO reacts
      with atomically adsorbed O atoms. These results show that nanosize Au clusters
      bound to oxide supports are not a necessary condition for Au-catalyzed, low
      temperature CO oxidation.

PMID- 16464074
TI  - Photo-CIDNP reveals differences in compaction of non-native states of lysozyme.
AB  - Photo-CIDNP effects interpreted for individual residues are used for the
      structural characterization of non-native ensembles of proteins, which is
      described in this paper. Two-dimensional photo-CIDNP experiments are compared to
      conventional HSQC spectra to elucidate the relative solvent exposure of the six
      tryptophan residues in non-native states of hen egg white lysozyme. The
      differential solvent accessibility of the tryptophan residues in non-native
      lysozyme coincides with the dynamical properties of these residues monitored for
      both backbone and side chain NH sides obtained from analysis of transverse
      relaxation measurements. These data can be interpreted in the context of the
      hydrophobic clustering around the tryptophan residues and is supported by the
      application of this method to the cluster breaking W62G mutant of lysozyme.

PMID- 16464075
TI  - Three-coordinate Co(I) provides access to unsaturated dihydrido-Co(III) and seven
      coordinate Co(V).
AB  - The three-coordinate, T-shaped Co(I) complex, PNPCo (PNP = [(tBu2PCH2SiMe2)2N-],
      is readily synthesized by magnesium reduction of divalent PNPCoCl. Triplet (S =
      1) PNPCo is coordinatively and electronically unsaturated and undergoes a
      thermally reversible oxidative addition reaction with H2, producing trivalent
      PNPCo(H)2. In contrast, the reaction with excess primary silane PhSiH3
      quantitatively generates the base-stabilized silylene Co(V) compound {kappa2
      tBu2PCH2Me2SiNSiMe2CH2tBu2P(H)Si=}Co(H)3(SiH2Ph)2.

PMID- 16464076
TI  - Nickel(0)-catalyzed isomerization of an aryne complex: formation of a dinuclear
      Ni(I) complex via C-H rather than C-F bond activation.
AB  - The reaction of the aryne complex (PEt3)2Ni(eta2-C6H2-4,5-F2) with a catalytic
      amount of Ni(PEt3)2 results in a dinuclear Ni(I) complex from the coupling of the
      isomer (PEt3)2Ni(eta2-C6H2-3,4-F2), obtained via rearrangement of the aromatic C
      H bonds, which demonstrates that Ni(PEt3)2 is kinetically capable of C-H bond
      activation, even in the presence of C-F bonds. The intermediate [(PEt3)2Ni]2(mu
      eta2:eta2-C6H2-4,5-F2) was isolated and crystallographically characterized; the
      mu-eta2:eta2-bonding mode observed is unprecedented in aryne chemistry.

PMID- 16464078
TI  - Catalytic, enantioselective [4 + 2]-cycloadditions of ketene enolates and o
      quinones: efficient entry to chiral, alpha-oxygenated carboxylic acid
      derivatives.
AB  - We report catalytic, enantioselective [4 + 2]-cycloadditions of o-quinones with
      ketene enolates (derived from readily available acid chlorides) using cinchona
      alkaloid derivatives as catalysts to produce products in high enantiomeric excess
      (ee) and good to excellent yields. The thermodynamic driving force for these
      reactions is due in part to the restoration of aromaticity to the products. The
      resulting chiral, bicycloadducts can be synthetically manipulated in a variety of
      useful ways, for example to provide a flexible synthesis of alpha-oxygenated
      carboxylic acid derivatives.

PMID- 16464077
TI  - Self-reporting fluorescent substrates of protein tyrosine kinases.
AB  - A new mechanistic principle by which protein tyrosine kinase substrates
      fluorescently report the introduction of a phosphate moiety has been developed.
      NMR was used to establish that tyrosine phosphorylation induces the disruption of
      pi-pi stacking interactions of the tyrosine moiety with a proximal fluorophore on
      the peptide substrate. We have demonstrated that (1) the peptide substrates
      described in this study are useful for a wide variety of different tyrosine
      kinases, (2) physiological concentrations of ATP can be employed (unlike the
      standard radioactive ATP kinase assays), thus providing a more realistic
      assessment of inhibitor potency, and (3) protein kinase self-activation can be
      observed in real-time.

PMID- 16464079
TI  - Isolation and crystal structures of two singlet bis(triarylamine) dications with
      nonquinoidal geometries.
AB  - We report the first structural data for bis(diarylamine) "bipolarons": we have
      isolated and crystallographically characterized salts of the dications obtained
      by two-electron oxidation of E-4,4'-bis[di(p-anisyl)amino]stilbene and E,E-2,5
      bis{4-[di(p-anisyl)amino]styryl}-3,4-di(n-butoxy)thiophene, [1](2+) and [2](2+)
      respectively. ESR, NMR, and magnetometry suggest both species have singlet ground
      states. X-ray structures, together with (1)H NMR coupling constants for [2](2+),
      indicate geometries in which the bond lengths are shifted toward a quinoidal
      pattern relative to that in the neutral species, but not to a fully quinoidal
      extent. In particular, the bond-length alternations across the vinylene bridging
      groups approach zero. DFT calculations with closed-shell singlet configurations
      reproduce the observed structures well. Our results indicate that singlet species
      for which one might expect quinoidal geometries (with differences of ca. 0.1 A
      between formally single and double bonds) on the basis of a limiting valence-bond
      representation of the structure can, in fact, show structures with significantly
      different patterns of bond lengths.

PMID- 16464080
TI  - Energy and photoinduced electron transfer in a wheel-shaped artificial
      photosynthetic antenna-reaction center complex.
AB  - Functional mimics of a photosynthetic antenna-reaction center complex comprising
      five bis(phenylethynyl)anthracene antenna moieties and a porphyrin-fullerene dyad
      organized by a central hexaphenylbenzene core have been prepared and studied
      spectroscopically. The molecules successfully integrate singlet-singlet energy
      transfer and photoinduced electron transfer. Energy transfer from the five
      antennas to the porphyrin occurs on the picosecond time scale with a quantum
      yield of 1.0. Comparisons with model compounds and theory suggest that the
      Forster mechanism plays a major role in the extremely rapid energy transfer,
      which occurs at rates comparable to those seen in some photosynthetic antenna
      systems. A through-bond, electron exchange mechanism also contributes. The
      porphyrin first excited singlet state donates an electron to the attached
      fullerene to yield a P(*+)-C(60)(*-) charge-separated state, which has a lifetime
      of several nanoseconds. The quantum yield of charge separation based on light
      absorbed by the antenna chromophores is 80% for the free base molecule and 96%
      for the zinc analogue.

PMID- 16464081
TI  - A highly active palladium catalyst for intermolecular hydroamination. Factors
      that control reactivity and additions of functionalized anilines to dienes and
      vinylarenes.
AB  - We report a catalyst for intermolecular hydroamination of vinylarenes that is
      substantially more active for this process than catalysts published previously.
      With this more reactive catalyst, we demonstrate that additions of amines to
      vinylarenes and dienes occur in the presence of potentially reactive functional
      groups, such as ketones with enolizable hydrogens, free alcohols, free carboxylic
      acids, free amides, nitriles, and esters. The catalyst for these reactions is
      generated from [Pd(eta(3)-allyl)Cl](2) (with or without added AgOTf) or
      [Pd(CH(3)CN)(4)](BF(4))(2) and Xantphos (9,9-dimethyl-4,5
      bis(diphenylphosphino)xanthene), which generates complexes with large P-Pd-P bite
      angles. Studies on the rate of the C-N bond-forming step that occurs by attack of
      amine on an eta(3)-phenethyl and an eta(3)-allyl complex were conducted to
      determine the effect of the bite angle on the rate of this nucleophilic attack.
      Studies on model eta(3)-benzyl complexes containing various bisphosphines showed
      that the nucleophilic attack was faster for complexes containing larger P-Pd-P
      bite angles. Studies of substituted unsymmetrical and unsubstituted symmetrical
      model eta(3)-allyl complexes showed that nucleophilic attack on complexes ligated
      by Xantphos was faster than on complexes bearing ligands with smaller bite angles
      and that nucleophilic attack on unsymmetrical allyl complexes with larger bite
      angle ligands was faster than on unsymmetrical allyl complexes with smaller bite
      angle ligands. However, monitoring of catalytic reactions of dienes by (31)P NMR
      spectroscopy showed that the concentration of active catalyst was the major
      factor that controlled rates for reactions of symmetrical dienes catalyzed by
      complexes of phosphines with smaller bite angles. The identity of the counterion
      also affected the rate of attack: reactions of allylpalladium complexes with
      chloride counterion occurred faster than reactions of allylpalladium complexes
      with triflate or tetrafluoroborate counterion. As is often observed, the dynamics
      of the allyl and benzyl complexes also depended on the identity of the
      counterion.

PMID- 16464083
TI  - Alkane C-H bond activation in zeolites: evidence for direct protium exchange.
AB  - The mechanism of alkane C-H bond activation in heterogeneous acid catalysis is
      unknown. (1)H solid-state NMR techniques have been used to simultaneously detect
      the reactivity of both catalyst and alkane reactant protons in a true in-situ
      experimental design. Specifically, the activation of isobutane C-H bonds by the
      solid acid zeolite HZSM-5 is directly observed, and the rate of proton transfer
      between the solid catalyst surface and gaseous isobutane is quantitatively
      measured using isotopic (1)H/(2)H exchange methods. An observable adsorption
      complex forms between the isobutane and the primary Bronsted acid site of ZSM-5,
      which leads to proton exchange between the zeolite surface and the isobutane
      methyl groups at temperatures (273 K) much lower than previously reported. The
      secondary acid site in ZSM-5 is less accessible to or less reactive with the
      isobutane molecule. Simultaneous detection of protium loss from the Bronsted acid
      site and protium gain by perdeuterated isobutane reveals a common rate constant
      equal to 4.1-4.6 x 10(-4) s(-1) at 298 K, but at lower temperatures, the
      transition between this and a much slower rate process is resolved. The measured
      activation energy for isobutane H/D exchange is 57 kJ/mol. In all experiments,
      the isobutane reagent was purified to eliminate any unsaturated impurities that
      might serve as initiators for carbenium-ion mechanisms, and the active catalyst
      was free of any organic contaminants that might serve as a source of unsaturated
      initiators. In total, our results are consistent with direct proton exchange
      between the zeolite surface and the methyl groups of isobutane.

PMID- 16464082
TI  - Highly active chiral ruthenium catalysts for asymmetric ring-closing olefin
      metathesis.
AB  - The synthesis of olefin metathesis catalysts containing chiral, monodentate N
      heterocyclic carbenes and their application to asymmetric ring-closing metathesis
      (ARCM) are reported. These catalysts retain the high levels of reactivity found
      in the related achiral variants (1a and 1b). Using the parent chiral catalysts 2a
      and 2b and derivatives that contain steric bulk in the meta positions of the N
      bound aryl rings (catalysts 3-5), five- through seven-membered rings were formed
      in up to 92% ee. The addition of sodium iodide to catalysts 2a-4a (to form 2b-4b
      in situ) caused a dramatic increase in enantioselectivity for many substrates.
      Catalyst 5a, which gave high enantiomeric excesses for certain substrates without
      the addition of NaI, could be used in loadings of < or =1 mol %. Mechanistic
      explanations for the large sodium iodide effect as well as possible mechanistic
      pathways leading to the observed products are discussed.

PMID- 16464084
TI  - Detection of second hydration shells in ionic solutions by XANES: computed
      spectra for Ni2+ in water based on molecular dynamics.
AB  - A general procedure to compute X-ray absorption near-edge structure (XANES)
      spectra within multiple-scattering theory starting from molecular dynamics (MD)
      structural data has been developed and applied to the study of a Ni(2+) aqueous
      solution. This method allows one to perform a quantitative analysis of the XANES
      spectra of disordered systems using a proper description of the thermal and
      structural fluctuations. The XANES spectrum of Ni(2+) in aqueous solution has
      been calculated using the structural information obtained from the MD simulations
      without carrying out any minimization in the structural parameter space. A very
      good reproduction of the experimental data was obtained including the second
      shell water molecules in the calculation, thus showing that the second hydration
      shell provides a detectable contribution to the XANES spectra of ionic solutions.
      The analysis including the first-shell cluster only permitted us to
      quantitatively determine the effect of disorder on the amplitude of the XANES
      spectra for molecular complexes. These results simultaneously confirm the
      reliability of the procedure and the structural results obtained from MD
      simulations. The combination of MD and XANES is found to be very helpful to get
      important new insights into the quantitative estimation of structural properties
      of disordered systems.

PMID- 16464086
TI  - Effect of pressure on a heavy-atom isotope effect of yeast alcohol dehydrogenase.
AB  - Hydrostatic pressure causes a monophasic decrease in the (13)C primary isotope
      effect expressed on the oxidation of benzyl alcohol by yeast alcohol
      dehydrogenase. The primary isotope effect was measured by the competitive method,
      using whole-molecule mass spectrometry. The effect is, therefore, an expression
      of isotopic discrimination on the kinetic parameter V/K, which measures substrate
      capture. Moderate pressure increases capture by activating hydride transfer, the
      transition state of which must therefore have a smaller volume than the free
      alcohol plus the capturing form of enzyme [Cho, Y.-K.; Northrop, D. B.
      Biochemistry 1999, 38, 7470-7475]. The decrease in the (13)C isotope effect with
      increasing pressure means that the transition state for hydride transfer from the
      heavy atom must have an even smaller volume, measured here to be 13 mL.mol(-1).
      The pressure data factor the kinetic isotope effect into a semiclassical reactant
      state component, with a null value of k(12)/k(13) = 1, and a transition-state
      component of Q(12)/Q(13) = 1.028 (borrowing Bell's nomenclature for hydrogen
      tunneling corrections). A similar experiment involving a deuterium isotope effect
      previously returned the same volume and null value, plus a pressure-sensitive
      isotope effect [Northrop, D. B.; Cho, Y.-K. Biochemistry 2000, 39, 2406-2412].
      Consistent with precedence in the chemical literature, the latter suggested a
      possibility of hydrogen tunneling; however, it is unlikely that carbon can engage
      in significant tunneling at ambient temperature. The fact that the decrease in
      activation volumes for hydride transfer is equivalent when one mass unit is added
      to the carbon end of a scissile C-H bond and when one mass unit is added to the
      hydrogen end is significant and suggests a common origin.

PMID- 16464085
TI  - Inhibition of HLA-DQ2-mediated antigen presentation by analogues of a high
      affinity 33-residue peptide from alpha2-gliadin.
AB  - Human leukocyte antigen DQ2 is a class II major histocompatibility complex
      protein that plays a critical role in the pathogenesis of Celiac Sprue by binding
      to epitopes derived from dietary gluten and triggering the inflammatory response
      of disease-specific T cells. Inhibition of DQ2-mediated antigen presentation in
      the small intestinal mucosa of Celiac Sprue patients therefore represents a
      potentially attractive mode of therapy for this widespread but unmet medical
      need. Starting from a pro-inflammatory, proteolytically resistant, 33-residue
      peptide, LQLQPFPQPELPYPQPELPYPQPELPYPQPQPF, we embarked upon a systematic effort
      to dissect the relationships between peptide structure and DQ2 affinity and to
      translate these insights into prototypical DQ2 blocking agents. Three structural
      determinants within the first 20 residues of this 33-mer peptide, including a
      PQPELPYPQ epitope, its N-terminal flanking sequence, and a downstream Glu
      residue, were found to be important for DQ2 binding. Guided by the X-ray crystal
      structure of DQ2, the L11 and L18 residues in the truncated 20-mer analogue were
      replaced with sterically bulky groups so as to retain high DQ2 affinity but
      abrogate T cell recognition. A dimeric ligand, synthesized by regiospecific
      coupling of the 20-mer peptide with a bifunctional linker, was identified as an
      especially potent DQ2 binding agent. Two such ligands were able to attenuate the
      proliferation of disease-specific T cell lines in response to gluten antigens
      and, therefore, represent prototypical examples of pharmacologically suitable DQ2
      blocking agents for the potential treatment of Celiac Sprue.

PMID- 16464087
TI  - Effect of molecular chirality on racemate stability: alpha-amino acids with
      nonpolar R groups.
AB  - A racemate of two opposite and resolvable enantiomers is generally assumed to be
      more stable than the corresponding conglomerate. Demonstrating this structure
      stability relation, however, has proved difficult owing to a sampling bias (data
      available only for systems whose racemates are stable enough to exist) and a
      possible kinetic bias (racemates may be easier to crystallize than conglomerates
      from racemic media). As a new approach to studying the relation, we determined
      how the relative stability of the conglomerate and the racemate changes with the
      molecule's degree of chirality in a series of alpha-amino acids with nonpolar R
      groups. We found that the excess energy of the conglomerate over the racemate,
      (E(C) - E(R)), increases with the size of the R group, a measure of the
      molecule's chirality. If valid in general, this relation demonstrates a tendency
      for chiral molecules to form racemates rather than conglomerates. Because of the
      entropy effect on crystal stability, however, the excess free energy of the
      conglomerate over the racemate, (G(C) - G(R)), shows no simple relation with the
      degree of chirality at the temperatures of study (-3 to 180 degrees C).

PMID- 16464088
TI  - Inhibition of thioredoxin and thioredoxin reductase by 4-hydroxy-2-nonenal in
      vitro and in vivo.
AB  - Lipid peroxidation is a cellular process that takes place under physiological
      conditions and particularly after oxidative stress. 4-Hydroxy-2-nonenal (HNE), a
      major end product of lipid peroxidation, is known to exert a multitude of
      biological effects and has high reactivity to various cellular components,
      including DNA and protein. The thioredoxin system, composed of the selenoenzyme
      thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, plays a key role in
      redox regulation and is involved in many signaling pathways. The selenocysteine
      (Sec) and cysteine (Cys) residues (Cys-496/Sec-497) in the active site of TrxR
      and a pair of Cys residues (Cys-32/Cys-35) in Trx are sensitive to various
      alkylating reagents. Herein, we report a mechanistic study on the inhibition of
      rat TrxR by HNE. The inhibition occurs with TrxR only in its reduced form and
      persists after removal of HNE. Inhibition of TrxR by HNE added to cultured HeLa
      cells is also observed. In addition, HNE inactivates reduced Escherichia coli Trx
      irreversibly. We proved that the redox residues (Cys-496/Sec-497 in TrxR and Cys
      32/Cys-35 in Trx) were primary targets for HNE modification. The covalent adducts
      formed between HNE and Trx were also confirmed by mass spectrum. Because the
      thioredoxin system is one of the core regulation enzymes of cells' function,
      inhibition of both TrxR and Trx by HNE provides a possibly novel mechanism for
      explanation of its cytotoxic effect and signaling activity, as well as the
      further damage indirectly caused under oxidative stress conditions.

PMID- 16464089
TI  - Cobalt(diamine)-catalyzed cross-coupling reaction of alkyl halides with
      arylmagnesium reagents: stereoselective constructions of arylated asymmetric
      carbons and application to total synthesis of AH13205.
AB  - A cobalt-diamine complex catalyzes the cross-coupling reactions of primary and
      secondary alkyl halides with aryl Grignard reagents. It is confirmed that
      oxidative addition of alkyl halide to cobalt proceeds via a radical process.
      Optically pure Ueno-Stork halo acetals undergo diastereoselective cross-coupling
      reactions, the products of which are transformed into optically active THF
      derivatives. A sequential radical cyclization/arylation reaction under cobalt
      catalysis provides extremely short access to a synthetic prostaglandin AH13205.

PMID- 16464091
TI  - Application of Badger's rule to heme and non-heme iron-oxygen bonds: an
      examination of ferryl protonation states.
AB  - To gain insight into the protonation state of enzymatic ferryl species we have
      examined the applicability of Badger's rule to heme and non-heme iron-oxygen
      bonds. Using density functional theory we have calculated r(e) and nu(e) for the
      Fe-O bonds of complexes with different axial ligands, iron-oxidation, oxygen
      protonation, and spin states. Our results indicate that Badger's rule holds for
      heme and non-heme oxo and hydroxo complexes. We find that the long Fe-O bonds
      that have been reported in the crystal structures of the ferryl forms of
      myoglobin, horseradish peroxidase, cytochrome c peroxidase, and catalase deviate
      substantially from the values predicted by Badger's rule, while the short Fe-O
      bonds obtained from X-ray absorption measurements are in good agreement with
      Badger's rule. In light of our analysis we conclude that the ferryl forms of
      myoglobin, horseradish peroxidase, and cytochrome c peroxidase are authentic
      iron(IV)oxos with Fe-O bonds on the order of 1.66 A and pKa's < 4.

PMID- 16464090
TI  - Spontaneous fibril formation by polyalanines; discontinuous molecular dynamics
      simulations.
AB  - Fibrillary protein aggregates rich in beta-sheet structure have been implicated
      in the pathology of several neurodegenerative diseases. In this work, we
      investigate the formation of fibrils by performing discontinuous molecular
      dynamics simulations on systems containing 12 to 96 model Ac-KA(14)K-NH(2)
      peptides using our newly developed off-lattice, implicit-solvent, intermediate
      resolution model, PRIME. We find that, at a low concentration, random-coil
      peptides assemble into alpha-helices at low temperatures. At intermediate
      concentrations, random-coil peptides assemble into alpha-helices at low
      temperatures and large beta-sheet structures at high temperatures. At high
      concentrations, the system forms beta-sheets over a wide range of temperatures.
      These assemble into fibrils above a critical temperature which decreases with
      concentration and exceeds the isolated peptide's folding temperature. At very
      high temperatures and all concentrations, the system is in a random-coil state.
      All of these results are in good qualitative agreement with those by Blondelle
      and co-workers on Ac-KA(14)K-NH(2) peptides. The fibrils observed in our
      simulations mimic the structural characteristics observed in experiments in terms
      of the number of sheets formed, the values of the intra- and intersheet
      separations, and the parallel peptide arrangement within each beta-sheet.
      Finally, we find that when the strength of the hydrophobic interaction between
      nonpolar side chains is high compared to the strength of hydrogen bonding,
      amorphous aggregates, rather than fibrillar aggregates, are formed.

PMID- 16464092
TI  - Functionalized gold nanoparticles as phosphorescent nanomaterials and sensors.
AB  - Ligand-capped gold nanoparticles were synthesized by capping monothiol
      derivatives of 2,2'-dipyridyl onto the surface of Au nanoparticles (Au-BT). The
      average size of the metal core is around 4 nm, with a shell of approximately 340
      bipyridine ligands around the Au nanoparticle. The high local concentration of
      the chelating ligands ( approximately 5 M) around the Au nanoparticle makes these
      particles excellent ion sponges, and their complexation with Eu(III)/Tb(III) ions
      yields phosphorescent nanomaterials. Absorption spectral studies confirm a 1:3
      complexation between Eu(III)/Tb(III) ions and bipyridines, functionalized on the
      surface of Au nanoparticles. The red-emitting Au-BT:Eu(III) complex exhibits a
      long lifetime of 0.36 ms with six line-like emission peaks, whereas the green
      emitting Au-BT:Tb(III) complex exhibits a lifetime of 0.7 ms with four line-like
      emission peaks. These phosphorescent nanomaterials, designed by linking
      BT:Eu(III) complexes to Au nanoparticles, were further utilized as sensors for
      metal cations. A dramatic decrease in the luminescence was observed upon addition
      of alkaline earth metal ions (Ca(2+), Mg(2+)) and transition metal ions (Cu(2+),
      Zn(2+), Ni(2+)), resulting from an isomorphous substitution of Eu(III) ions,
      whereas the luminescence intensity was not influenced by the addition of Na(+)
      and K(+) ions. Direct interaction of bipyridine-capped Au nanoparticles with
      Cu(2+) ions brings the nanohybrid systems closer, leading to the formation of
      three-dimensional superstructures. Strong interparticle plasmon interactions were
      observed in these closely spaced Au nanoparticles.

PMID- 16464093
TI  - Thermodynamics of interactions of water-soluble porphyrins with RNA duplexes.
AB  - We characterized the interactions of meso-tetrakis(4N-(2-hydroxyethyl)pyridinium
      4-yl) porphyrin (TEtOHPyP4), meso-tetrakis(4N-allylpyridinium-4-yl) porphyrin
      (TAlPyP4), and meso-tetrakis(4N-metallylpyridinium-4-yl) porphyrin (TMetAlPyP4)
      with the poly(rA)poly(rU) and poly(rI)poly(rC) RNA duplexes between 18 and 45
      degrees C by employing circular dichroism, light absorption, and fluorescence
      intensity spectroscopic measurements. Our results suggest that TEtOHPyP4 and
      TAlPyP4 intercalate into the poly(rA)poly(rU) and poly(rI)poly(rC) host duplexes,
      while TMetAlPyP4 associates with these RNA duplexes by forming outside-bound,
      self-stacked aggregates. We used our temperature-dependent absorption titration
      data to determine the binding constants and stoichiometry for each porphyrin-RNA
      binding event studied in this work. From the temperature dependences of the
      binding constants, we calculated the binding free energies, DeltaG(b),
      enthalpies, DeltaH(b), and entropies, DeltaS(b). For each RNA duplex, the binding
      enthalpy, DeltaH(b), is the most favorable for TEtOHPyP4 (an intercalator)
      followed by TAlPyP4 (an intercalator) and TMetAlPyP4 (an outside binder). On the
      other hand, for each duplex, external self-stacking of TMetAlPyP4 produces the
      most favorable change in entropy, DeltaS(b), followed by the intercalators
      TAlPyP4 and TEtOHPyP4. Thus, our results suggest that the thermodynamic profile
      of porphyrin-RNA binding may correlate with the binding mode. This correlation
      reflects the differential nature of molecular forces that stabilize/destabilize
      the two modes of binding-intercalation versus external self-stacking along the
      host duplex.

PMID- 16464094
TI  - Electroreduction of a series of alkylcobalamins: mechanism of stepwise reductive
      cleavage of the Co-C bond.
AB  - The electrochemical (EC) reduction mechanism of methylcobalamin (Me-Cbl) in a
      mixed DMF/MeOH solvent in 0.2 M tetrabutylammonium fluoroborate electrolyte was
      studied as a function of temperature and solvent ratio vs a nonaqueous
      Ag/AgCl/Cl(-) reference electrode. Double-potential-step chronoamperometry
      allowed the rate constant of the subsequent homogeneous reaction to be measured
      over the temperature range from 0 to -80 degrees C in 40:60 and 50:50 DMF:MeOH
      ratios. Activation enthalpies are 5.8 +/- 0.5 and 7.6 +/- 0.3 kcal/mol in the
      40:60 and 50:50 mixtures of DMF/MeOH, respectively. Digital simulation and curve
      fitting for an EC mechanism using a predetermined homogeneous rate constant of
      5.5 x 10(3) s(-1) give E degrees' = -1.466 V, k degrees = 0.016 cm/s, and alpha =
      0.77 at 20 degrees C for a quasi-reversible electrode process. Digital simulation
      of the results of Lexa and Saveant (J. Am. Chem. Soc. 1978, 100, 3220-3222) shows
      that the mechanism is a series of stepwise homogeneous equilibrium processes with
      an irreversible step following the initial electron transfer (ET) and allows
      estimation of the equilibrium and rate constants of these reactions. An electron
      coupling matrix element of H(kA) = (4.7 +/- 1.1) x 10(-4) eV ( approximately 46
      J/mol) is calculated for the nonadiabatic ET step for reduction to the radical
      anion. A reversible bond dissociation enthalpy for homolytic cleavage of Me-Cbl
      is calculated as 31 +/- 2 kcal/mol. The voltammetry of the ethyl-, n-propyl-, n
      butyl-, isobutyl-, and adenosyl-substituted cobalamin was studied, and estimated
      reversible redox potentials were correlated with Co-C bond distances as
      determined by DFT (B3LYP/ LANL2DZ) calculations.

PMID- 16464095
TI  - Structural insights into homo- and heterotropic allosteric coupling in the zinc
      sensor S. aureus CzrA from covalently fused dimers.
AB  - The Zn(II)/Co(II)-sensing transcriptional repressor, Staphylococcus aureus CzrA,
      is a homodimer containing a symmetry-related pair of subunit-bridging tetrahedral
      N(3)O metal sensor coordination sites. A metal-induced quaternary structural
      change within the homodimer is thought to govern the biological activity of this
      and other metal sensor proteins. Here, we exploit covalent (Gly(4)Ser)(n)()
      linkers of variable length in "fused" CzrAs, where n = 1 (designated 5L-fCzrA), 2
      (10L-fCzrA), or 3 (15L-fCzrA), as molecular rulers designed to restrict any
      quaternary structural changes that are associated with metal binding and metal
      mediated allosteric regulation of DNA binding to varying degrees. While 15L-fCzrA
      exhibits properties most like homodimeric CzrA, shortening the linker in 10L
      fCzrA abolishes negative homotropic cooperativity of Zn(II) binding and reduces
      DNA binding affinity of the apoprotein significantly. Decreasing the linker
      length further in 5L-fCzrA effectively destroys one metal site altogether and
      further reduces DNA binding affinity. However, Zn(II) negatively regulates DNA
      binding of all fCzrAs, with allosteric coupling free energies (DeltaG(1)(c)) of
      4.6, 3.1, and 2.7 kcal mol(-1) for 15L-, 10L-, and 5L-fCzrAs, respectively.
      Introduction of a single nonliganding H97N substitution into either the N
      terminal or C-terminal protomer domain in 10L-fCzrA results in DeltaG(1)(c) = 2.6
      kcal mol(-1) or approximately 83% that of 10L-fCzrA; in contrast, homodimeric
      H97N CzrA gives DeltaG(1)(c) = 0. (1)H-(15)N HSQC spectra acquired for wt-, 10L
      fCzrA and H97N 10L-fCzrA in various Zn(II) ligation states reveal that the
      allosteric change of the protomer domains within the fused dimer is independent
      and not concerted. Thus, occupancy of a single metal site by Zn(II) introduces
      asymmetry into the CzrA homodimer that leads to significant allosteric regulation
      of DNA binding.

PMID- 16464096
TI  - The nature of the H3O+ hydronium ion in benzene and chlorinated hydrocarbon
      solvents. Conditions of existence and reinterpretation of infrared data.
AB  - Salts of the C(3v) symmetric hydronium ion, H(3)O(+), have been obtained in the
      weakly basic solvents benzene, dichloromethane, and 1,2-dichloroethane. This is
      made possible by using carborane counterions of the type CHB(11)R(5)X(6)(-) (R =
      H, Me, Cl; X = Cl, Br, I) because they combine the three required properties of a
      suitable counterion: very low basicity, low polarizability, and high chemical
      stability. The existence of the H(3)O(+) ion requires the formation of three more
      or-less equivalent, medium-to-strong H-bonds with solvent or anion bases. With
      the least basic anions such as CHB(11)Cl(11)(-), IR spectroscopy indicates that
      C(3v) symmetric trisolvates of formulation [H(3)O(+) .3Solv] are formed with
      chlorocarbon solvents and benzene, the latter with the formation of pi bonds.
      When the solvents and anions have comparable basicity, contact ion pairs of the
      type [H(3)O(+).nSolv.Carborane] are formed and close to C(3v) symmetry is
      retained. The conditions for the existence of the H(3)O(+) ion are much more
      exacting than previously appreciated. Outside of the range of solvent basicity
      bounded at the lower end by dichloromethane and the upper end by tributyl
      phosphate, and with anions that do not meet the stringent requirements of weak
      basicity, low polarizability of high chemical stability, lower symmetry species
      are formed. One H-bond from H(3)O(+) to the surrounding bases becomes stronger
      than the other two. The distortion from C(3v) symmetry is minor for bases weaker
      than dichloromethane. For bases stronger than tributyl phosphate, H(2)O-H(+)-B
      type species are formed that are more closely related to the H(5)O(2)(+) ion than
      to H(3)O(+). IR data allow criteria to be defined for the existence of the
      symmetric H(3)O(+) ion. This includes a linear dependence between the frequencies
      of nu(max)(OH) and delta(OH(3)) within the ranges 3010-2536 cm(-1) for
      nu(max)(OH) and 1597-1710 cm(-1) for delta(OH(3)). This provides a simple way to
      assess the correctness of the formulation of the proton state in monohydrated
      acids. In particular, the 30-year-old citation classic of the IR spectrum
      believed to arise from H(3)O(+) SbCl(6)(-) is re-interpreted in terms of
      (H(2)O)(x)().HSbCl(6) hydrates. The correctness of the hydronium ion formulation
      in crystalline H(3)O(+)A(-) salts (A(-) = Cl(-), NO(3)(-)) is confirmed,
      although, when A(-) is a fluoroanion, distortions from C(3)(v)() symmetry are
      suggested.

PMID- 16464097
TI  - Molecular engineering and measurements to test hypothesized mechanisms in single
      molecule conductance switching.
AB  - Six customized phenylene-ethynylene-based oligomers have been studied for their
      electronic properties using scanning tunneling microscopy to test hypothesized
      mechanisms of stochastic conductance switching. Previously suggested mechanisms
      include functional group reduction, functional group rotation, backbone ring
      rotation, neighboring molecule interactions, bond fluctuations, and hybridization
      changes. Here, we test these hypotheses experimentally by varying the molecular
      designs of the switches; the ability of the molecules to switch via each
      hypothetical mechanism is selectively engineered into or out of each molecule. We
      conclude that hybridization changes at the molecule-surface interface are
      responsible for the switching we observe.

PMID- 16464098
TI  - Alternating copolymerization of fluoroalkenes with carbon monoxide.
AB  - The palladium-catalyzed alternating copolymerization of fluoroalkenes,
      represented as CH(2)=CH-CH(2)-C(n)F(2n+1), with CO was performed using (R,S)
      BINAPHOS (2e) as a ligand. The CH(2)-C(n)F(2n+1) group is the most
      electronegative substituent ever reported for the copolymerization (Taft's sigma
      value of 0.90 for CH(2)CF(3)). The copolymer obtained from CH(2)=CH-CH(2)
      C(8)F(17) (1a) existed as a mixture of polyspiroketal and polyketone, while that
      from CH(2)=CH-CH(2)-C(4)F(9) (1b) was a pure polyspiroketal, as was revealed by
      infrared and (13)C-CP/MAS NMR spectroscopies. The terminal structure of the
      polymer from 1b was confirmed by MALDI-TOF MS spectrometry. Detailed NMR studies
      suggested that the much higher reactivity with (R,S)-BINAPHOS (2e) than that with
      the conventional ligand DPPP (2a) can be attributed to the unique 1,2-insertion
      of the fluoroalkene into acylpalladium species. The existence of an
      electronegative substituent on the alpha-carbon of the palladium center is
      successfully avoided in the 1,2-insertion mechanism.

PMID- 16464099
TI  - Building up key segments of N-glycans in the gas phase: intrinsic structural
      preferences of the alpha(1,3) and alpha(1,6) dimannosides.
AB  - The intrinsic conformer specific vibrational spectra of two important subunits of
      the core pentasaccharide of N-linked glycans, the alpha(1,3) and alpha(1,6)
      dimannosides, have been recorded in the gas phase. Coupling these measurements
      with a computational exploration of their conformational landscapes has enabled
      their conformational assignment and has identified characteristic vibrational
      signatures associated with particular conformational families-including those
      that do or do not display inter-ring hydrogen bonding across the glycosidic
      linkage. In addition, the IR spectra of the monosaccharide moieties provide
      benchmarks, through which the conformational assignments can be refined. This
      introduces a general concept of modularity and secondary structure in
      oligosaccharides--essential for the success of similar studies on larger
      oligosaccharides in the future.

PMID- 16464100
TI  - Resonating valence bond ground state in oxygen-functionalized phenalenyl-based
      neutral radical molecular conductors.
AB  - We report the preparation, crystallization, and solid-state characterization of
      the first two members of a new family of spiro-bis(1,9-disubstituted
      phenalenyl)boron neutral radicals based solely on oxygen functionalization, and
      we show that this strategy significantly lowers the electrochemical
      disproportionation potentials (DeltaE), in comparison with other spiro-bis(1,9
      disubstituted phenalenyl)boron salts. In the solid state, these radicals pack in
      a continuous array of pi-pi-stacked phenalenyl units with very short
      intermolecular carbon...carbon contacts. These two radicals are among the most
      highly conducting neutral organic solids, with room temperature conductivities
      reaching 0.3 S/cm. Magnetic susceptibility measurements show that the radicals do
      not exist as isolated free radicals, and there is significant spin-spin
      interaction between the molecules in the solid state as expected from the crystal
      structures and the calculated band structures; the solid-state properties are
      best rationalized in terms of the resonating valence bond model.

PMID- 16464102
TI  - Kinetics and mechanism of methane, methanol, and dimethyl ether C-H activation
      with electrophilic platinum complexes.
AB  - The relative rates of C-H activation of methane, methanol, and dimethyl ether by
      [(N-N)PtMe(TFE-d(3))](+) ((N-N) = ArN=C(Me)-C(Me)=NAr; Ar = 3,5-di-tert
      butylphenyl, TFE-d(3) = CF(3)CD(2)OD) (2(TFE)) were determined. Methane
      activation kinetics were conducted by reacting 2(TFE)-(13)C with 300-1000 psi of
      methane in single-crystal sapphire NMR tubes; clean second-order behavior was
      obtained (k = 1.6 +/- 0.4 x 10(-3) M(-1) s(-1) at 330 K; k = 2.7 +/- 0.2 x 10(-4)
      M(-1) s(-1) at 313 K). Addition of methanol to solutions of 2(TFE) rapidly
      establishes equilibrium between methanol (2(MeOD)) and trifluoroethanol (2(TFE))
      adducts, with methanol binding preferentially (K(eq) = 0.0042 +/- 0.0006). C-H
      activation gives [(N-N)Pt(CH(2)OD)(MeOD)](+) (4), which is unstable and reacts
      with [(RO)B(C(6)F(5))(3)](-) to generate a pentafluorophenyl platinum complex.
      Analysis of kinetics data for reaction of 2 with methanol yields k = 2.0 +/- 0.2
      x 10(-3) M(-1) s(-1) at 330 K, with a small kinetic isotope effect (k(H)/k(D) =
      1.4 +/- 0.1). Reaction of dimethyl ether with 2(TFE) proceeds similarly (K(eq) =
      0.023 +/- 0.002, 313 K; k = 5.5 +/- 0.5 x 10(-4) M(-1) s(-1), k(H)/k(D) = 1.5 +/-
      0.1); the product obtained is a novel bis(alkylidene)-bridged platinum dimer,
      [(diimine)Pt(mu-CH(2))(mu-(CH(OCH(3)))Pt(diimine)](2+) (5). Displacement of TFE
      by a C-H bond appears to be the rate-determining step for all three substrates;
      comparison of the second-order rate constants (k((methane))/k((methanol)) =
      1/1.3, 330 K; k((methane))/k((dimethy)(l e)(ther)) = 1/2.0, 313 K) shows that
      this step is relatively unselective for the C-H bonds of methane, methanol, or
      dimethyl ether. This low selectivity agrees with previous estimates for
      oxidations with aqueous tetrachloroplatinate(II)/hexachloroplatinate(IV),
      suggesting a similar rate-determining step for those reactions.

PMID- 16464101
TI  - Probing the structural requirements of peptoids that inhibit HDM2-p53
      interactions.
AB  - Many cellular processes are controlled by protein-protein interactions, and
      selective inhibition of these interactions could lead to the development of new
      therapies for several diseases. In the area of cancer, overexpression of the
      protein, human double minute 2 (HDM2), which binds to and inactivates the protein
      p53, has been linked to tumor aggressiveness and drug resistance. In general,
      inhibition of protein-protein interactions with synthetic molecules is
      challenging and currently remains a largely uncharted area for drug development.
      One strategy to create inhibitors of protein-protein interactions is to recreate
      the three-dimensional arrangement of side chains that are involved in the binding
      of one protein to another, using a nonnatural scaffold as the attachment point
      for the side chains. In this study, we used oligomeric peptoids as the scaffold
      to begin to develop a general strategy in which we could rationally design
      synthetic molecules that can be optimized for inhibition of protein-protein
      interactions. Structural information on the HDM2-p53 complex was used to design
      our first class of peptoid inhibitors, and we provide here, in detail, the
      strategy to modify peptoids with the appropriate side chains that are effective
      inhibitors of HDM2-p53 binding. While we initially tried to develop rigid,
      helical peptoids as HDM2 binders, the best inhibitors were surprisingly peptoids
      that lacked any helix-promoting groups. These results indicate that starting with
      rigid peptoid scaffolds may not always be optimal to develop new inhibitors.

PMID- 16464103
TI  - Electronic structure of binuclear mixed valence copper azacryptates derived from
      integrated advanced EPR and DFT calculations.
AB  - Binuclear, mixed valence copper complexes with a [Cu(+1)(.5), Cu(+1)(.5)] redox
      state and S = (1)/(2) can be stabilized with rigid azacryptand ligands. In this
      system the unpaired electron is delocalized equally over the two copper ions, and
      it is one of the very few synthetic models for the electron mediating Cu(A) site
      of nitrous oxide reductase and cytochrome c oxidase. The spatial and electronic
      structures of the copper complex in frozen solution were obtained from the
      magnetic interactions, namely the g-tensor and the (63,65)Cu, (14)N, (2)H, and
      (1)H hyperfine couplings, in combination with density functional theory (DFT)
      calculations. The magnetic interactions were determined from continuous wave (CW)
      electron paramagnetic resonance (EPR), pulsed electron nuclear double resonance
      (ENDOR), two-dimensional TRIPLE, and hyperfine sublevel correlation spectroscopy
      (HYSCORE) carried out at W-band or/and X-band frequencies. The DFT calculated g
      and Cu hyperfine values were in good agreement with the experimental values
      showing that the structure in solution is indeed close to that of the optimized
      structure. Then, the DFT calculated hyperfine parameters were used as guidelines
      and starting points in the simulations of the various experimental ENDOR spectra.
      A satisfactory agreement with the experimental results was obtained for the (14)N
      hyperfine and quadrupole interactions. For (1)H the DFT calculations gave good
      predictions for the hyperfine tensor orientations and signs, and they were also
      successful in reproducing trends in the magnitude of the various proton hyperfine
      couplings. These, in turn, were very useful for ENDOR signals assignments and
      served as constraints on the simulation parameters.

PMID- 16464104
TI  - Phase behavior of a phospholipid/fatty acid/water mixture studied in atomic
      detail.
AB  - Molecular dynamics simulations have been used to study the phase behavior of a
      dipalmitoylphosphatidylcholine (DPPC)/palmitic acid (PA)/water 1:2:20 mixture in
      atomic detail. Starting from a random solution of DPPC and PA in water, the
      system adopts either a gel phase at temperatures below approximately 330 K or an
      inverted hexagonal phase above approximately 330 K in good agreement with
      experiment. It has also been possible to observe the direct transformation from a
      gel to an inverted hexagonal phase at elevated temperature (approximately 390 K).
      During this transformation, a metastable fluid lamellar intermediate is observed.
      Interlamellar connections or stalks form spontaneously on a nanosecond time scale
      and subsequently elongate, leading to the formation of an inverted hexagonal
      phase. This work opens the possibility of studying in detail how the formation of
      nonlamellar phases is affected by lipid composition and (fusion) peptides and,
      thus, is an important step toward understanding related biological processes,
      such as membrane fusion.

PMID- 16464105
TI  - De novo structure-based design of bisurea hosts for tetrahedral oxoanion guests.
AB  - This paper presents a computational approach to the deliberate design of improved
      host architectures. De novo molecule building software, HostDesigner, is
      interfaced with molecular mechanics software, GMMX, providing a tool for
      generating and screening millions of potential structures. The efficacy of this
      computer-aided design methodology is illustrated with a search for bisurea
      podands that are structurally organized for complexation with tetrahedral
      oxoanions.

PMID- 16464106
TI  - Experimental and computational investigation of the uncatalyzed rearrangement and
      elimination reactions of isochorismate.
AB  - The versatile biosynthetic intermediate isochorismate decomposes in aqueous
      buffer by two competitive pathways, one leading to isoprephenate by a facile
      Claisen rearrangement and the other to salicylate via elimination of the
      enolpyruvyl side chain. Computation suggests that both processes are concerted
      but asynchronous pericyclic reactions, with considerable C-O cleavage in the
      transition state but relatively little C-C bond formation (rearrangement) or
      hydrogen atom transfer to the enolpyruvyl side chain (elimination). Kinetic
      experiments show that rearrangement is roughly 8-times more favorable than
      elimination. Moreover, transfer of the C2 hydrogen atom to C9 was verified by
      monitoring the decomposition of [2-(2)H]isochorismate, which was prepared
      chemoenzymatically from labeled shikimate, by (2)H NMR spectroscopy and observing
      the appearance of [3-(2)H]pyruvate. Finally, the isotope effects obtained with
      the C2 deuterated substrate are in good agreement with calculations assuming
      pericyclic reaction mechanisms. These results provide a benchmark for mechanistic
      investigations of isochorismate mutase and isochorismate pyruvate lyase, the
      enzymes that respectively catalyze the rearrangement and elimination reactions in
      plants and bacteria.

PMID- 16464107
TI  - Effective disruption of phosphoprotein-protein surface interaction using Zn(II)
      dipicolylamine-based artificial receptors via two-point interaction.
AB  - Protein phosphorylation is ubiquitously involved in living cells, and it is one
      of the key events controlling protein-protein surface interactions, which are
      essential in signal transduction cascades. We now report that the small molecular
      receptors bearing binuclear Zn(II)-Dpa can strongly bind to a bis-phosphorylated
      peptide in a cross-linking manner under neutral aqueous conditions when the
      distance between the two Zn(II) centers can appropriately fit in that of the two
      phosphate groups of the phosphorylated peptide. The binding property was
      quantitatively determined by ITC (isothermal titration calorimetry), induced CD
      (circular dichroism), and NMR. On the basis of these findings, we demonstrated
      that these types of small molecules were able to effectively disrupt the
      phosphoprotein-protein interaction in a phosphorylated CTD peptide and the Pin1
      WW domain, a phosphoprotein binding domain, at a micromolar level. The strategy
      based on a small molecular disruptor that directly interacts with phosphoprotein
      is unique and should be promising in developing a designer inhibitor for
      phosphoprotein-protein interaction.

PMID- 16464108
TI  - Carbon monoxide promoted reductive elimination of hydrogen from Tp' platinum
      complexes.
AB  - Acid-assisted reductive elimination of hydrogen from Tp'PtH(3) and of methane and
      hydrogen from Tp'PtMeH(2) (Tp' = hydridotris(3,5-dimethylpyrazolyl)borate) is
      examined herein. Loss of H(2) is observed from solutions containing platinum(IV)
      complexes of the type Tp'Pt(R)(H)(2) (R = Me, H) upon protonation and addition of
      a ligand such as CO. Results of kinetic studies on reductive elimination of H(2)
      and formation of [kappa(2)-(HTp')Pt(R)(L)][BAr'(4)] products from intermediates
      derived from Tp'Pt(R)(H)(2) precursors are described. Elimination appears to
      occur from cationic 6-coordinate [kappa(2)-(HTp')Pt(R)(H)(2)(L)][BAr'(4)]
      species.

PMID- 16464109
TI  - A reversible pH-driven DNA nanoswitch array.
AB  - An array of surface-immobilized proton-fueled DNA nanomachines is reversibly
      actuated by cycling of the solution pH between 4.5 and 9, producing a
      conformational change between a four-stranded and a double-stranded structure,
      which elongates or shortens the separation distance between the 5' and 3' end of
      the DNA. By labeling the DNA 3' end with a fluorophore and immobilizing it onto a
      thin-gold surface through its 5' thiol modification, the nanoscale motion of the
      DNA produces mechanical work to lift up and bring down the fluorophore from the
      gold surface by at least 2.5 nm and transduces this motion into an optical "on
      and-off" nanoswitch.

PMID- 16464110
TI  - Thioindigo dyes: highly accurate visible spectra with TD-DFT.
AB  - The structure and visible spectra of a large panel of thioindigo dyes and
      derivatives have been evaluated using a TD-PBE0/6-311+G(2d,p)//PBE0/6-311G(d,p)
      approach explicitly taking bulk solvent effects into account by means of the
      polarizable continuum model. The influence of the solvent characteristics, the
      trans-cis isomerization, and the chemical substitution on the benzene rings have
      been investigated. In addition, hemi-thioindigo dyes, thiazine-indigo,
      chromophore-like molecules, and selenoindigo have been considered. Though the
      relative oscillator strengths of the two allowed visible transitions in the
      nonplanar cis isomers are not always correctly reproduced by theory, the
      agreement between theoretical and experimental results is far above expectations.
      For the 170 cases studied, we obtained a mean unsigned error on the predicted
      lambda(max) limited to 6.9 nm or 0.03 eV, with only 6 (4) cases for which the
      difference exceeds 20 nm (0.10 eV). These errors are 1 order of magnitude smaller
      than what has previously been reported for indigoids. A linear correlation
      between the central double bond length and the lambda(max) has been established,
      while the bond length and vibrational frequency of the carbonyl groups do not
      correlate with the thioindigo color. The higher excitation energies of the cis
      conformers, compared to the trans structures, result from a less stabilized LUMO
      in the former case. Indeed, for cis thioindigo, the two electron-rich (in the
      excited state) carbonyl units lie close to each other.

PMID- 16464111
TI  - Electrochemistry of immobilized redox enzymes: kinetic characteristics of NADH
      oxidation catalysis at diaphorase monolayers affinity immobilized on electrodes.
AB  - In the class of NADH:acceptor oxidoreductases, the diaphorase from Bacillus
      stearothermophilusis a particularly promising enzyme for sensing NADH, and
      indirectly a great number of analytes, when coupled with a NAD-dependent
      dehydrogenase as well as for the design of mono- and multienzyme affinity
      sensors. The design and rational optimization of such systems require devising
      immobilization procedures that prevent dramatic losses of the enzymatic activity
      and a full kinetic characterization of the immobilized enzyme system. Two
      immobilization procedures are described, which involve recognition of the
      biotinylated diaphorase by a monolayer of neutravidin adsorbed on the electrode
      surface either directly or through the intermediacy of a monolayer of
      biotinylated rabbit immunoglobulin. Thorough kinetic characterization of the two
      systems is derived from cyclic voltammetric responses. A precise estimate of the
      enzyme coverages is obtained after comparing the enzyme kinetics of the
      immobilized and the homogeneous system.

PMID- 16464112
TI  - Experimental and density functional theoretical investigations of linkage
      isomerism in six-coordinate FeNO(6) iron porphyrins with axial nitrosyl and nitro
      ligands.
AB  - A critical component of the biological activity of NO and nitrite involves their
      coordination to the iron center in heme proteins. Irradiation (330 < lambda < 500
      nm) of the nitrosyl-nitro compound (TPP)Fe(NO)(NO(2)) (TPP =
      tetraphenylporphyrinato dianion) at 11 K results in changes in the IR spectrum
      associated with both nitro-to-nitrito and nitrosyl-to-isonitrosyl linkage
      isomerism. Only the nitro-to-nitrito linkage isomer is obtained at 200 K,
      indicating that the isonitrosyl linkage isomer is less stable than the nitrito
      linkage isomer. DFT calculations reveal two ground-state conformations of
      (porphine)Fe(NO)(NO(2)) that differ in the relative axial ligand orientations
      (i.e., GS parallel and GS perpendicular). In both conformations, the FeNO group
      is bent (156.4 degrees for GS parallel, 159.8 degrees for GS perpendicular) for
      this formally {FeNO}(6) compound. Three conformations of the nitrosyl-nitrito
      isomer (porphine)Fe(NO)(ONO) (MSa parallel, MSa perpendicular, and MSa(L)) and
      two conformations of the isonitrosyl-nitro isomer (porphine)Fe(ON)(NO(2)) (MSb
      parallel and MSb perpendicular) are identified, as are three conformations of the
      double-linkage isomer (porphine)Fe(ON)(ONO) (MSc parallel, MSc perpendicular,
      MSc(L)). Only 2 of the 10 optimized geometries contain near-linear FeNO (MSa(L))
      and FeON (MSc(L)) bonds. The energies of the ground-state and isomeric structures
      increase in the order GS < MSa < MSb < MSc. Vibrational frequencies for all of
      the linkage isomers have been calculated, and the theoretical gas-phase
      absorption spectrum of (porphine)Fe(NO)(NO(2)) has been analyzed to obtain
      information on the electronic transitions responsible for the linkage
      isomerization. Comparison of the experimental and theoretical IR spectra does not
      provide evidence for the existence of a double linkage isomer of
      (TPP)Fe(NO)(NO(2)).

PMID- 16464113
TI  - Highly enantioselective synthesis of glycidic amides using camphor-derived
      sulfonium salts. Mechanism and applications in synthesis.
AB  - The reactions of a range of amide-stabilized sulfur ylides derived from readily
      available camphor-derived sulfonium salts for the synthesis of glycidic amides
      have been studied. Primary, secondary, and tertiary amides were tested, and it
      was found that the highest enantioselectivities were observed with tertiary
      amides, which provided glycidic amides in good to excellent yields, exclusive
      trans selectivity, and excellent enantioselectivities. The reaction was general
      for aromatic aldehydes, but aliphatic aldehydes gave more variable
      enantioselectivities. The epoxy amides could be converted cleanly into epoxy
      ketones by treatment with organolithium reagents. We were also able to effect
      selective ring opening of the epoxy amides with a variety of nucleophiles,
      followed by hydrolysis of the amide to yield the corresponding carboxylic acid.
      This methodology was applied to the total synthesis of the target compound SK&F
      104353. A combination of crossover experiments and theoretical calculations has
      revealed that the rate- and selectivity-determining step is ring closure, not
      betaine formation as was the case for phenyl-stabilized ylides.

PMID- 16464115
TI  - Solid-state 35/37Cl NMR spectroscopy of hydrochloride salts of amino acids
      implicated in chloride ion transport channel selectivity: opportunities at 900
      MHz.
AB  - The results of a detailed systematic chlorine solid-state NMR study of several
      hydrochloride salts of amino acids implicated in chloride ion transport channel
      selectivity are reported. (35)Cl and (37)Cl NMR spectra have been obtained for
      stationary and/or magic-angle spinning powdered samples of the following
      compounds on 500 and/or 900 MHz spectrometers: DL-arginine HCl monohydrate, L
      lysine HCl, L-serine HCl, L-glutamic acid HCl, L-proline HCl, L-isoleucine HCl, L
      valine HCl, L-phenylalanine HCl, and glycine HCl. Spectral analyses provide
      information on the anisotropic properties and relative orientations of the
      chlorine electric field gradient and chemical shift (CS) tensors, which are
      intimately related to the local molecular and electronic structure. Data obtained
      at 900 MHz provide unique examples of the effects of CS anisotropy on the NMR
      spectrum of a quadrupolar nucleus. The range of chlorine quadrupolar coupling
      constants (C(Q)) measured, -6.42 to 2.03 MHz, demonstrates the sensitivity of
      this parameter to the chloride ion environment and suggests the applicability of
      chlorine solid-state NMR as a novel experimental tool for defining chloride
      binding environments in larger ion channel systems. Salts of hydrophobic amino
      acids are observed to tend to exhibit larger values of C(Q) than salts of
      hydrophilic amino acids. A simple model for rationalizing the observed trend in
      C(Q) is proposed. For salts for which neutron diffraction structures are
      available, we identify a quantum chemical method which reproduces experimental
      values of C(Q) with a root-mean-square deviation of 0.1 MHz and a correlation
      coefficient of 0.9998. On the basis of this, chlorine NMR tensors are predicted
      for the Cl(-) binding site in ClC channels.

PMID- 16464114
TI  - Cancer cell imaging and photothermal therapy in the near-infrared region by using
      gold nanorods.
AB  - Due to strong electric fields at the surface, the absorption and scattering of
      electromagnetic radiation by noble metal nanoparticles are strongly enhanced.
      These unique properties provide the potential of designing novel optically active
      reagents for simultaneous molecular imaging and photothermal cancer therapy. It
      is desirable to use agents that are active in the near-infrared (NIR) region of
      the radiation spectrum to minimize the light extinction by intrinsic chromophores
      in native tissue. Gold nanorods with suitable aspect ratios (length divided by
      width) can absorb and scatter strongly in the NIR region (650-900 nm). In the
      present work, we provide an in vitro demonstration of gold nanorods as novel
      contrast agents for both molecular imaging and photothermal cancer therapy.
      Nanorods are synthesized and conjugated to anti-epidermal growth factor receptor
      (anti-EGFR) monoclonal antibodies and incubated in cell cultures with a
      nonmalignant epithelial cell line (HaCat) and two malignant oral epithelial cell
      lines (HOC 313 clone 8 and HSC 3). The anti-EGFR antibody-conjugated nanorods
      bind specifically to the surface of the malignant-type cells with a much higher
      affinity due to the overexpressed EGFR on the cytoplasmic membrane of the
      malignant cells. As a result of the strongly scattered red light from gold
      nanorods in dark field, observed using a laboratory microscope, the malignant
      cells are clearly visualized and diagnosed from the nonmalignant cells. It is
      found that, after exposure to continuous red laser at 800 nm, malignant cells
      require about half the laser energy to be photothermally destroyed than the
      nonmalignant cells. Thus, both efficient cancer cell diagnostics and selective
      photothermal therapy are realized at the same time.

PMID- 16464116
TI  - Conductance of single alkanedithiols: conduction mechanism and effect of molecule
      electrode contacts.
AB  - The conductance of single alkanedithiols covalently bound to gold electrodes has
      been studied by statistical analysis of repeatedly created molecular junctions.
      For each molecule, the conductance histogram reveals two sets of well-defined
      peaks, corresponding to two different conductance values. We have found that (1)
      both conductance values decrease exponentially with the molecular length with an
      identical decay constant, beta approximately equal to 0.84 A(-1), but with a
      factor of 5 difference in the prefactor of the exponential function. (2) The
      current-voltage curves of the two sets can be fit with the Simmons tunneling
      model. (3) Both conductance values are independent of temperature (between -5 and
      60 degrees C) and the solvent. (4) Despite the difference in the conductance, the
      forces required to break the molecular junctions are the same, 1.5 nN. These
      observations lead us to believe that the conduction mechanism in alkanedithiols
      is due to electron tunneling or superexchange via the bonds along the molecules,
      and the two sets of conductance peaks are due to two different microscopic
      configurations of the molecule-electrode contacts.

PMID- 16464117
TI  - Strategies for electrooptic film fabrication. Influence of pyrrole-pyridine-based
      dibranched chromophore architecture on covalent self-assembly, thin-film
      microstructure, and nonlinear optical response.
AB  - The new dibranched, heterocyclic "push-pull" chromophores bis{1-(pyridin-4-yl)-2
      [2-(N-methylpyrrol-5-yl)]ethane}methane (1), 1-(pyrid-4-yl)-2-(N-methyl-5
      formylpyrrol-2-yl)ethylene (2), {1-(N-methylpyridinium-4-yl)-2-[2-(N-methylpyrrol
      5-yl)]ethane}{(1-(pyridin-4-yl)-2-[2-(N-methylpyrrol-5-yl)]ethane}methane (3), N
      methyl-2-[1-(N-methylpyrid-4-yl)ethen-2-yl]-5-[pyrid-4-yl]ethen-2-yl]pyrrole
      iodide (4), bis{1-(N-methyl-4-pyridinio)-2-[2-(N-methylpyrrol-5
      yl)]ethane}methane iodide (5), and N-methyl-2,5-[1-(N-methylpyrid-4-yl)ethen-2
      yl]pyrrole iodide (6) have been synthesized and characterized. The neutral (1 and
      2) and monomethyl salts (3 and 4) undergo chemisorptive reaction with iodobenzyl
      functionalized surfaces to afford chromophore monolayers SA-1/SA-2 and SA-3/SA-4,
      respectively. Molecular structures and other physicochemical properties have been
      defined by (1)H NMR, optical spectroscopy, and XRD. Thin-film characterization by
      a variety of techniques (optical spectroscopy, specular X-ray reflectivity,
      atomic force microscopy, X-ray photoelectron spectroscopy, and angle-dependent
      polarized second harmonic generation) underscore the importance of the
      chromophore molecular architecture as well as film growth method on film
      microstructure and optical/electrooptic response.

PMID- 16464119
TI  - Anatomical double-bundle anterior cruciate ligament reconstruction.
AB  - A careful review of the literature suggests that a significant number of patients
      undergoing anterior cruciate ligament (ACL) reconstruction have less than optimal
      results. Although overall outcomes of ACL reconstruction are favourable, there
      remains considerable room for improvement. Anatomically, the ACL consists of two
      major functional bundles, the anteromedial and the posterolateral bundle.
      Biomechanically, both bundles contribute significantly to the anterior and the
      rotational stability of the knee. Therefore, anatomical double-bundle ACL
      reconstruction techniques may further improve the outcomes in ACL surgery. Our
      preferred technique for arthroscopic double-bundle ACL reconstruction includes
      the use of two femoral and two tibial tunnels to restore both the anteromedial
      and the posterolateral bundle of the ACL and their anatomical footprints at their
      tibial and femoral insertion site. We use two tibialis anterior tendon allografts
      for the restoration of the two ACL bundles. Clinical long-term outcome studies
      may focus on the evaluation of functional outcomes, restoration of anterior and
      rotational knee stability, and the risk of degenerative osteoarthritis of the
      knee joint following anatomical double-bundle ACL reconstruction versus single
      bundle ACL reconstruction.

PMID- 16464120
TI  - The anti-hypertensive effects of exercise: integrating acute and chronic
      mechanisms.
AB  - It is anticipated that hypertension will afflict up to a third of the worldwide
      population by the year 2025. Therefore, cost-effective treatment strategies are
      essential to control this disease. Exercise has been associated with anti
      hypertensive benefits, but despite extensive research the optimal exercise dose
      (training frequency, intensity and time) required to lower blood pressure and
      maintain normotensive status remains unclear. This article explores the
      interrelationships between acute and chronic mechanisms that have been linked to
      the anti-hypertensive benefits of exercise and proposes that the optimal exercise
      dosage may depend on the interplay between these mechanisms and the effects of
      exercise on independent risk markers of hypertension. Therefore, the correct
      exercise dose for the treatment of hypertension should be prescribed on an
      individual basis. Future work should examine post-exercise hypotension effects in
      relation to exercise training in hypertensive populations and both acute and
      longitudinal training studies should be conducted that incorporate independent
      risk factors of hypertension as co-variables into their analysis on blood
      pressure effects.

PMID- 16464121
TI  - Is there an optimal training intensity for enhancing the maximal oxygen uptake of
      distance runners?: empirical research findings, current opinions, physiological
      rationale and practical recommendations.
AB  - The maximal oxygen uptake (V-dotO(2max)) is considered an important physiological
      determinant of middle- and long-distance running performance. Little information
      exists in the scientific literature relating to the most effective training
      intensity for the enhancement of V-dotO(2max) in well trained distance runners.
      Training intensities of 40-50% V-dotO(2max) can increase V-dotO(2max)
      substantially in untrained individuals. The minimum training intensity that
      elicits the enhancement of V-dotO(2max) is highly dependent on the initial V
      dotO(2max), however, and well trained distance runners probably need to train at
      relative high percentages of V-dotO(2max) to elicit further increments. Some
      authors have suggested that training at 70-80% V-dotO(2max) is optimal. Many
      studies have investigated the maximum amount of time runners can maintain 95-100%
      V-dotO(2max) with the assertion that this intensity is optimal in enhancing V
      dotO(2max). Presently, there have been no well controlled training studies to
      support this premise. Myocardial morphological changes that increase maximal
      stroke volume, increased capillarisation of skeletal muscle, increased myoglobin
      concentration, and increased oxidative capacity of type II skeletal muscle fibres
      are adaptations associated with the enhancement of V-dotO(2max). The strength of
      stimuli that elicit adaptation is exercise intensity dependent up to V
      dotO(2max), indicating that training at or near V-dotO(2max) may be the most
      effective intensity to enhance V-dotO(2max) in well trained distance runners.
      Lower training intensities may induce similar adaptation because the
      physiological stress can be imposed for longer periods. This is probably only
      true for moderately trained runners, however, because all cardiorespiratory
      adaptations elicited by submaximal training have probably already been elicited
      in distance runners competing at a relatively high level.Well trained distance
      runners have been reported to reach a plateau in V-dotO(2max) enhancement;
      however, many studies have demonstrated that the V-dotO(2max) of well trained
      runners can be enhanced when training protocols known to elicit 95-100% V
      dotO(2max) are included in their training programmes. This supports the premise
      that high-intensity training may be effective or even necessary for well trained
      distance runners to enhance V-dotO(2max). However, the efficacy of optimised
      protocols for enhancing V-dotO(2max) needs to be established with well controlled
      studies in which they are compared with protocols involving other training
      intensities typically used by distance runners to enhance V-dotO(2max).

PMID- 16464123
TI  - Epicondylar injury in sport: epidemiology, type, mechanisms, assessment,
      management and prevention.
AB  - Epicondylar injuries in sports with overhead or repetitive arm actions are
      frequent and often severe. Acute injury that results in inflammation should be
      termed epicondylitis and is usually the result of large valgus forces with medial
      distraction and lateral compression. Epicondylosis develops over a longer period
      of time from repetitive forces and results in structural changes in the tendon.
      Epicondylalgia refers to elbow pain at either the medial or lateral epicondyl of
      the elbow related to tendinopathy of the common flexor or extensor tendon origins
      at these points. Pain is usually associated with gripping, resisted wrist
      extension and certain movements such as in tennis and golf, hence the common
      terms 'tennis elbow' (lateral epicondylsis) and 'golf elbow' (medial
      epicondylossi). A variety of assessment and diagnostic tools are available to aid
      the clinician in their comprehensive evaluation of the patient to ensure correct
      diagnosis and the appropriate conservative or surgical management strategy.
      Corticosteroids and elbow straps are often used for treatment; however, there is
      only very limited prospective clinical or experimental evidence for their
      effectiveness. The most effective modalities of treatment are probably rest (the
      absence of painful activity) combined with cryotherapy in the acute stage then
      NSAIDs and heat in its various modalities including ultrasound. Cortisone
      injections may be used to create a pain-free window of opportunity to optimise
      the athletes' rehabilitation exercises. Medical practitioners should have a good
      understanding of the mechanisms of injury in order to help treat and prevent the
      re-occurrence of injuries. More emphasis by medical and sport science personnel
      working with coaches and athletes needs to be placed on prevention of elbow
      injury in sport through improved joint strength, biomechanically sound sport
      technique and use of appropriate sport equipment.

PMID- 16464122
TI  - Neural adaptations to resistive exercise: mechanisms and recommendations for
      training practices.
AB  - It is generally accepted that neural factors play an important role in muscle
      strength gains. This article reviews the neural adaptations in strength, with the
      goal of laying the foundations for practical applications in sports medicine and
      rehabilitation. An increase in muscular strength without noticeable hypertrophy
      is the first line of evidence for neural involvement in acquisition of muscular
      strength. The use of surface electromyographic (SEMG) techniques reveal that
      strength gains in the early phase of a training regimen are associated with an
      increase in the amplitude of SEMG activity. This has been interpreted as an
      increase in neural drive, which denotes the magnitude of efferent neural output
      from the CNS to active muscle fibres. However, SEMG activity is a global measure
      of muscle activity. Underlying alterations in SEMG activity are changes in motor
      unit firing patterns as measured by indwelling (wire or needle) electrodes. Some
      studies have reported a transient increase in motor unit firing rate. Training
      related increases in the rate of tension development have also been linked with
      an increased probability of doublet firing in individual motor units. A doublet
      is a very short interspike interval in a motor unit train, and usually occurs at
      the onset of a muscular contraction. Motor unit synchronisation is another
      possible mechanism for increases in muscle strength, but has yet to be definitely
      demonstrated. There are several lines of evidence for central control of training
      related adaptation to resistive exercise. Mental practice using imagined
      contractions has been shown to increase the excitability of the cortical areas
      involved in movement and motion planning. However, training using imagined
      contractions is unlikely to be as effective as physical training, and it may be
      more applicable to rehabilitation. Retention of strength gains after dissipation
      of physiological effects demonstrates a strong practice effect. Bilateral
      contractions are associated with lower SEMG and strength compared with unilateral
      contractions of the same muscle group. SEMG magnitude is lower for eccentric
      contractions than for concentric contractions. However, resistive training can
      reverse these trends. The last line of evidence presented involves the notion
      that unilateral resistive exercise of a specific limb will also result in
      training effects in the unexercised contralateral limb (cross-transfer or cross
      education). Peripheral involvement in training-related strength increases is much
      more uncertain. Changes in the sensory receptors (i.e. Golgi tendon organs) may
      lead to disinhibition and an increased expression of muscular force. Agonist
      muscle activity results in limb movement in the desired direction, while
      antagonist activity opposes that motion. Both decreases and increases in co
      activation of the antagonist have been demonstrated. A reduction in antagonist co
      activation would allow increased expression of agonist muscle force, while an
      increase in antagonist co-activation is important for maintaining the integrity
      of the joint. Thus far, it is not clear what the CNS will optimise: force
      production or joint integrity. The following recommendations are made by the
      authors based on the existing literature. Motor learning theory and imagined
      contractions should be incorporated into strength-training practice. Static
      contractions at greater muscle lengths will transfer across more joint angles.
      Submaximal eccentric contractions should be used when there are issues of muscle
      pain, detraining or limb immobilisation. The reversal of antagonists (antagonist
      to-agonist) proprioceptive neuromuscular facilitation contraction pattern would
      be useful to increase the rate of tension development in older adults, thus
      serving as an important prophylactic in preventing falls. When evaluating the
      neural changes induced by strength training using EMG recording, antagonist EMG
      activity should always be measured and evaluated.

PMID- 16464124
TI  - Golf injuries: a review of the literature.
AB  - Golf is one of a few activities that people of all ages and skill level can play.
      Injury as with all sports can occur. The low back is the most common injury
      sustained whilst playing golf, and the dynamic action of the golf swing is a
      major contributing factor to injury. The golf swing is a complex movement that
      utilises the whole body in a coordinated fashion and when repeated frequently can
      result in injury. Injury can be overuse or traumatic in nature. Overuse injuries
      predominate in the professional golfer, and amateur golfer injury tends to occur
      secondary to an incorrect golf swing. Upper limb injuries are also common due to
      their role in linking the fast moving golf club with the power-generating torso.
      Fortunately, injury from a club or ball strike is rare. More common are the
      overuse injuries associated with the back, neck and shoulder. Most golf injury
      data have been collected retrospectively and further epidemiological study of a
      prospective nature is required to determine injury incidence and factor relating
      to the onset of injury.

PMID- 16464125
TI  - p16(INK4a) prevents centrosome dysfunction and genomic instability in primary
      cells.
AB  - Aneuploidy, frequently observed in premalignant lesions, disrupts gene dosage and
      contributes to neoplastic progression. Theodor Boveri hypothesized nearly 100
      years ago that aneuploidy was due to an increase in centrosome number (multipolar
      mitoses) and the resultant abnormal segregation of chromosomes. We performed
      immunocytochemistry, quantitative immunofluorescence, karyotypic analysis, and
      time-lapse microscopy on primary human diploid epithelial cells and fibroblasts
      to better understand the mechanism involved in the production of supernumerary
      centrosomes (more than two microtubule nucleating bodies) to directly demonstrate
      that the presence of supernumerary centrosomes in genomically intact cells
      generates aneuploid daughter cells. We show that loss of p16(INK4a) generates
      supernumerary centrosomes through centriole pair splitting. Generation of
      supernumerary centrosomes in human diploid epithelial cells was shown to nucleate
      multipolar spindles and directly drive production of aneuploid daughter cells as
      a result of unequal segregation of the genomic material during mitosis. Finally,
      we demonstrate that p16(INK4a) cooperates with p21 through regulation of cyclin
      dependent kinase activity to prevent centriole pair splitting. Cells with loss of
      p16(INK4a) activity have been found in vivo in histologically normal mammary
      tissue from a substantial fraction of healthy, disease-free women. Demonstration
      of centrosome dysfunction in cells due to loss of p16(INK4a) suggests that, under
      the appropriate conditions, these cells can become aneuploid. Gain or loss of
      genomic material (aneuploidy) may provide the necessary proproliferation and
      antiapoptotic mechanisms needed for the earliest stages of tumorigenesis.

PMID- 16464127
TI  - High-light-induced changes on photosynthesis, pigments, sugars, lipids and
      antioxidant enzymes in freshwater (Nostoc spongiaeforme) and marine (Phormidium
      corium) cyanobacteria.
AB  - We studied the effects of high-light exposure (500 micromol m(-2) s(-1) of
      photosynthetic active radiation) on the cyanobacteria Nostoc spongiaeforme
      Agardh, a fresh-water alga, and Phormidium corium Agardh (Gomont), a marine alga,
      with respect to photosynthesis, pigments, sugar content, lipid peroxidation,
      fatty acids composition, antioxidant enzymes activity and DNA. It was seen that
      the ratio of variable fluorescence (Fv) to maximum fluorescence (Fm), which is
      indicative of photosynthetic efficiency, decreased because of the light
      treatment. The damage to photosynthesis occurred in the antenna system and the
      photosynthetic II reaction center. Photobleaching of photosynthetic pigments was
      also observed. High-light treatment also resulted in decreased sugar content,
      which was probably due to the effect on photosynthesis. Peroxidation of membrane
      lipids, indicating oxidative damage to lipids and a high level of unsaturation in
      the cell membrane, was also observed. The activity of antioxidant enzyme
      superoxide dismutase and ascorbate peroxidase was increased, probably as a result
      of oxidative damage observed in the form of lipid peroxidation. Quantitative
      decreases in phospholipid and glycolipid levels were also observed. The level of
      unsaturated fatty acids in total lipids and glycolipids remained unchanged in
      both species; however, the level of saturated fatty acids decreased, which
      slightly changed the ratio in favor of unsaturated fatty acids. Degradation of
      DNA was also observed in both species. There was a transient plateau 2-4 h after
      exposure to high-light treatment in the Fv/Fm ratio and in levels of
      phycobilisome pigments, sugars and antioxidant enzymes after an initial decrease
      1 h after the treatment. These findings may indicate a period of partial
      adaptation to high light that is due to the efficiency of protective processes
      operational in the two species, which subsequently failed after a longer exposure
      duration of 4-6 h.

PMID- 16464128
TI  - Autophagy: a forty-year search for a missing membrane source.

PMID- 16464126
TI  - Gene losses during human origins.
AB  - Pseudogenization is a widespread phenomenon in genome evolution, and it has been
      proposed to serve as an engine of evolutionary change, especially during human
      origins (the "less-is-more" hypothesis). However, there has been no comprehensive
      analysis of human-specific pseudogenes. Furthermore, it is unclear whether
      pseudogenization itself can be selectively favored and thus play an active role
      in human evolution. Here we conduct a comparative genomic analysis and a
      literature survey to identify 80 nonprocessed pseudogenes that were inactivated
      in the human lineage after its separation from the chimpanzee lineage. Many
      functions are involved among these genes, with chemoreception and immune response
      being outstandingly overrepresented, suggesting potential species-specific
      features in these aspects of human physiology. To explore the possibility of
      adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate
      proteinase participating in inflammatory and innate immune response to
      endotoxins. We provide population genetic evidence that the nearly complete
      fixation of a null allele at CASPASE12 has been driven by positive selection,
      probably because the null allele confers protection from severe sepsis. We
      estimate that the selective advantage of the null allele is about 0.9% and the
      pseudogenization started shortly before the out-of-Africa migration of modern
      humans. Interestingly, two other genes related to sepsis were also pseudogenized
      in humans, possibly by selection. These adaptive gene losses might have occurred
      because of changes in our environment or genetic background that altered the
      threat from or response to sepsis. The identification and analysis of human
      specific pseudogenes open the door for understanding the roles of gene losses in
      human origins, and the demonstration that gene loss itself can be adaptive
      supports and extends the "less-is-more" hypothesis.

PMID- 16464129
TI  - Oscillations, intercellular coupling, and insulin secretion in pancreatic beta
      cells.

PMID- 16464130
TI  - Pandemic influenza: the inside story.

PMID- 16464132
TI  - An energy-saving development initiative increases birth rate and childhood
      malnutrition in rural Ethiopia.
AB  - BACKGROUND: Evolutionary life history theory predicts that, in the absence of
      contraception, any enhancement of maternal condition can increase human
      fertility. Energetic trade-offs are likely to be resolved in favour of maximizing
      reproductive success rather than health or longevity. Here we find support for
      the hypothesis that development initiatives designed to improve maternal and
      child welfare may also incur costs associated with increased family sizes if they
      do not include a family planning component. METHODS AND FINDINGS: Demographic and
      anthropometric data were collected in a rural Ethiopian community benefiting from
      a recent labour-saving development technology that reduces women's energetic
      expenditure (n = 1,976 households). Using logistic hazards models and general
      linear modelling techniques, we found that whilst infant mortality has declined,
      the birth rate has increased, causing greater scarcity of resources within
      households. CONCLUSIONS: This study is, to our knowledge, the first to
      demonstrate a link between a technological development intervention and an
      increase in both birth rate and childhood malnutrition. Women's nutritional
      status was not improved by the energy-saving technology, because energy was
      diverted into higher birth rates. We argue that the contribution of biological
      processes to increased birth rates in areas of the developing world without
      access to modern contraception has been overlooked. This highlights the continued
      need for development programmes to be multisectoral, including access to and
      promotion of contraception.

PMID- 16464134
TI  - The Million Death Study in India: cam it help in monitoring the millennium
      development goals?

PMID- 16464135
TI  - Seeking prescribing patterns in rural Crete: a pharmacoepidemiological study from
      a primary care area.
AB  - INTRODUCTION: Deliberation of drug prescribing patterns is essential in an effort
      to improve prescribing standards and quality of care. It is vital for pharmaco
      epidemiological research. In this study, data from GPs' practices was used to
      explore variation in the prescribing patterns in a rural area of Crete. This
      article reports the findings with respect to the patients' age, sex and
      diagnoses, and discusses them with the broad aim of identifying areas for
      practice improvement. METHODS: One thousand prescriptions, issued during a one
      year period, were pre-selected from the area of Anogia Health Centre in Crete,
      Greece. A copy of each pre-selected prescription was made, and a short pre-tested
      questionnaire with supplementary information about the prescription was filled.
      Age, gender, prescription through a third person's intervention, and renewal of
      an old prescription, were registered on this questionnaire. Drugs were classified
      according to the International Classification of Primary Care--Drugs, and
      diagnoses according to the International Classification of Primary Care. RESULTS:
      The vast majority of prescriptions, namely n = 285 (74.2%) for male and n = 481
      (78.1%) for female patients, were prescribed for individuals between the ages of
      50 and 89 years. The 10 most commonly recorded diagnoses were found in 54.2% of
      the studied prescriptions for the male population, although only 47% for the
      female. Hypertension, respiratory infections, and ischaemic heart disease were,
      over all, the most commonly recorded diseases. The drugs commonly recorded for
      both sexes were paracetamol and furosemide, as well as some antibiotics. Analysis
      of the prescribing data revealed that more than one in every three prescriptions
      was prescribed through a third-person contact and 69.8% (n = 698) of the
      prescriptions were renewal of an older one. For more than 51% of the cases, the
      patients asked only for a prescription. The diagnosis 'oral contraceptive' was
      absent in the study, while there was a large consumption of antibiotics.
      CONCLUSION: The prescribing patterns illustrated in this study present both
      similarities with and differences from the registered patterns in other studies.
      The recognition of these patterns is an essential tool for the GPs who are
      serving rural areas of Crete, and formulation of practical guidelines on the
      drugs most often prescribed is anticipated to improve the primary care
      physicians' performance.

PMID- 16464136
TI  - Practical design and implementation considerations in pay-for-performance
      programs.

PMID- 16464133
TI  - A single siRNA suppresses fatal encephalitis induced by two different
      flaviviruses.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) and West Nile virus (WNV) are
      neurotropic flaviviruses that can cause acute encephalitis with a high fatality
      rate. Currently there is no effective treatment for these infections. METHODS AND
      FINDINGS: We tested RNA interference (RNAi)-based intervention to suppress lethal
      JE and WN encephalitis in mice. To induce RNAi, we used either lentivirally
      expressed short hairpin RNA (shRNA) or synthetic short interfering RNA (siRNA).
      As target, we selected the cd loop-coding sequence in domain II of the viral
      Envelope protein, which is highly conserved among all flaviviruses because of its
      essential role in membrane fusion. Using as a target a species-specific sequence
      in the cd loop that is conserved only among the different strains of either JEV
      or WNV, we could achieve specific protection against the corresponding virus.
      However, by targeting a cross-species conserved sequence within the cd loop, we
      were able to protect mice against encephalitis induced by both viruses. A single
      intracranial administration of lentivirally delivered shRNA or lipid-complexed
      siRNA before viral challenge or siRNA treatment after viral challenge was
      sufficient for protection against lethal encephalitis. CONCLUSIONS: RNAi-based
      intervention affords near complete protection from both JEV- and WNV- induced
      encephalitis in mice. Our results show, to our knowledge for the first time, that
      siRNA can be used as a broad-spectrum antiviral agent for treating encephalitis
      caused by multiple related viruses.

PMID- 16464137
TI  - Managing the metric vs managing the patient: the physician's view of pay for
      performance.

PMID- 16464138
TI  - Effects of a program for coordinated care of advanced illness on patients,
      surrogates, and healthcare costs: a randomized trial.
AB  - OBJECTIVE: To evaluate the Advanced Illness Coordinated Care Program (AICCP),
      delivered by allied health personnel to improve care for patients coping with
      advanced illness and in need of preparation for end-of-life (EOL) care. STUDY
      DESIGN: Clinical trial involving 275 patients and 143 surrogates in 6 settings
      who were randomly assigned to the AICCP or usual care (UC). METHODS: The AICCP
      participants met with a care coordinator for assistance with provider
      communication, care coordination, and support. The AICCP was evaluated for
      effects on satisfaction with care, advance planning, consistency of care with
      patient preferences, and healthcare costs. RESULTS: The AICCP increased patient
      satisfaction with care and communication (P = .03), and AICCP surrogates reported
      fewer problems with provider support (P = .03). More AICCP than UC participants
      completed an advance directive (AD) (69.4% vs 48.4%; P = .006), and the AICCP
      group completed more ADs per participant (P = .01). Median time to AD
      documentation was 46 days for AICCP and 238 days for UC (P = .02). There was no
      difference in survival (AICCP 43% vs UC 42%). Six-month costs were lower with
      AICCP than with UC (12,123 US dollars vs 16,295 US dollars); however, the
      difference did not reach statistical significance. CONCLUSIONS: The AICCP
      improved satisfaction with care and helped patients develop and revise more ADs,
      sooner, without affecting mortality. This program may be delivered in a range of
      managed care, fee-for-service, and group-model settings.

PMID- 16464139
TI  - Management training of physician executives, their leadership style, and care
      management performance: an empirical study.
AB  - OBJECTIVE: To examine associations between management training of physician
      executives and their leadership styles, as well as effectiveness in achieving
      disease management goals. STUDY DESIGN: Cross-sectional national survey. METHODS:
      Executive directors of community health centers (269 respondents; response rate =
      40.9%) were surveyed regarding their perceptions of the medical director's
      leadership, and for quantitative information on the center's achievement of
      clinical (mostly disease management) goals. The dependent variables were the
      medical director's scores (as perceived by the executive director) on
      transformational, transactional, and laissez-faire leadership, effectiveness,
      satisfaction with the leader, and subordinate extra effort, using an adapted
      Multifactor Leadership Questionnaire (43 items; 5-point Likert scale). The
      independent variable was the medical director's management training status.
      RESULTS: Compared with medical directors with < 30 days of inservice training,
      medical directors with an MHA, MPH, or MBA, or > or =30 days of in-service
      training, had 0.32, 0.35, 0.30, 0.36, and 0.37 higher scores on transformational
      leadership, transactional leadership, rated effectiveness, satisfaction, and
      subordinate extra effort, respectively, and 0.31 lower score on laissez-faire
      leadership (all P < .001). Medical directors without management degrees but with
      > or =30 days of in-service training had 0.34, 0.36, 0.50, and 0.47 higher scores
      on transformational leadership, transactional leadership, rated effectiveness,
      and satisfaction with the leader (all P < .02). Our data previously had
      demonstrated that medical directors' transformational leadership significantly
      influences achievement of disease management goals. CONCLUSION: Training may
      enable physician executives to develop leadership styles that are effective in
      influencing clinical providers' adoption of disease management guidelines under
      managed care.

PMID- 16464140
TI  - A comparison of comorbidity measurements to predict healthcare expenditures.
AB  - OBJECTIVE: To compare the performance of the Elixhauser, Charlson, and RxRisk-V
      comorbidity indices and several simple count measurements, including counts of
      prescriptions, physician visits, hospital claims, unique prescription classes,
      and diagnosis clusters. STUDY DESIGN: Each measurement was calculated using
      claims data during a 1-year period before the initial filling of an
      antihypertensive medication among 20 378 members of a managed care organization.
      The primary outcome variable was the log-transformed sum of prescription,
      physician, and hospital expenditures in the year following the prescription
      encounter. METHODS: In addition to descriptive statistics and Spearman rank
      correlations between measurements, the predictive performance was determined
      using linear regression models and corresponding adjusted R(2) statistics.
      RESULTS: The Charlson index and the Elixhauser index performed similarly
      (adjusted R(2) = 0.1172 and 0.1148, respectively), while the prescription claims
      based RxRisk-V (adjusted R(2) = 0.1573) outperformed both. An age- and gender
      adjusted regression model that included a count of diagnosis clusters was the
      best individual predictor of payments (adjusted R(2) = 0.1814). This outperformed
      age- and gender-adjusted models of the number of unique prescriptions filled
      (adjusted R(2) = 0.1669), number of prescriptions filled (R(2) = 0.1573), number
      of physician visits (adjusted R(2) = 0.1546), logtransformed prior healthcare
      payments (adjusted R(2) = 0.1359), and number of hospital claims (adjusted R(2) =
      0.1115). CONCLUSION: Simple count measurements appear to be better predictors of
      future expenditures than the comorbidity indices, with a count of diagnosis
      clusters being the single best predictor of future expenditures among the
      measurements examined.

PMID- 16464141
TI  - Improvements in identifying persistent asthma patients using HEDIS data.

PMID- 16464154
TI  - Genome projects and the functional-genomic era.
AB  - The problems we face today in public health as a result of the -- fortunately --
      increasing age of people and the requirements of developing countries create an
      urgent need for new and innovative approaches in medicine and in agronomics.
      Genomic and functional genomic approaches have a great potential to at least
      partially solve these problems in the future. Important progress has been made by
      procedures to decode genomic information of humans, but also of other key
      organisms. The basic comprehension of genomic information (and its transfer)
      should now give us the possibility to pursue the next important step in life
      science eventually leading to a basic understanding of biological information
      flow; the elucidation of the function of all genes and correlative products
      encoded in the genome, as well as the discovery of their interactions in a
      molecular context and the response to environmental factors. As a result of the
      sequencing projects, we are now able to ask important questions about sequence
      variation and can start to comprehensively study the function of expressed genes
      on different levels such as RNA, protein or the cell in a systematic context
      including underlying networks. In this article we review and comment on current
      trends in large-scale systematic biological research. A particular emphasis is
      put on technology developments that can provide means to accomplish the tasks of
      future lines of functional genomics.

PMID- 16464155
TI  - Gel-based versus gel-free proteomics: a review.
AB  - With the sequencing of the genome of over 150 organisms, the field of biology has
      been revolutionised. Instead of studying one gene or protein at the time, it is
      now possible to study the effect of physiological or pathological changes on the
      expression of all genes or proteins in the organism. Proteomics aims at the
      simultaneous analysis of all proteins expressed by a cell, tissue or organism in
      a specific physiological condition. Because proteins are the effector molecules
      in all organisms, it is evident that changes in the physiological condition of an
      organism will be reflected by changes in protein expression and/or processing.
      Since the formulation of the concept of proteomics in the mid 90's proteomics has
      relied heavily on 2 dimensional gel electrophoresis (2DGE) for the separation and
      visualization of proteins. 2DGE, however, has a number of inherent drawbacks.
      2DGE is costly, fairly insensitive to low copy proteins and cannot be used for
      the entire proteome. Therefore, over the years, several gel-free proteomics
      techniques have been developed to either fill the gaps left by 2DGE or to
      entirely abolish the gel based techniques. This review summarizes the most
      important gel-free and gel-based proteomics techniques and compares their
      advantages and drawbacks.

PMID- 16464156
TI  - Proteomics in nutrition and health.
AB  - Proteomics, the comprehensive analysis of a protein complement in a cell, tissue
      or biological fluid at a given time, has been enabled by quantum leaps in mass
      spectrometric technology, which allowed identification of large, involatile
      biomolecules. Over the last two decades, this discipline evolved from the sole
      delivery of protein identities to a platform, which reveals clues to function
      through e.g. characterisation of protein modifications and interactions as well
      as through quantitative proteomics, i.e. the global comparison of protein amounts
      between two defined biological states. Proteomics is an integral part and key
      player in the family of -omic disciplines as there are genomics (gene analysis),
      transcriptomics (gene expression analysis) and metabolomics (metabolite
      profiling). Considering the complexity, dynamics and protein concentration range
      of any given proteome, proteomics is the most challenging -omic discipline and
      requires the most sophisticated analysis pipeline. Proteomics represents an
      established technology in the pharmaceutical industry mainly for biomarker and
      drug target discovery. The potential of proteomics for research in the food
      industry is increasingly being recognised and the employment of proteomic
      approaches to nutrition and health issues is now emerging. This review summarizes
      (i) major technological achievements in mass spectrometry and proteomics, (ii)
      deliverables of proteomics in the context of nutrition and health, and (iii)
      applications of proteomics, and -- if appropriate -- transcriptomics to the
      research fields of digestive health, obesity and diabetes, immunity and allergy,
      probiotics, milk, and food preference.

PMID- 16464157
TI  - The peptidomics concept.
AB  - Peptides are a paramount example of how nature diversifies from one single gene
      to release multiple, regulated functionalities at the desired sites and time. To
      achieve this, peptides are sequentially generated by a complex network of more
      than 500 proteases, acting at intracellular sites, upon secretion, in
      extracellular environments, and, finally, serving (regulated) degradation. This
      cycle of maturation, activation, and degradation points out that the peptidome is
      mechanistically linked to the proteome: the distribution between both is
      regulated by proteases and counter-regulated by protease inhibitors. Given the
      high diversity of peptides in living systems and their involvement in key
      regulatory processes, a need for improved peptide discovery, ideally combining
      peptide sequence identification with peptide profiling, has emerged. Standard
      proteomic approaches are not suitable for a systematic peptide analysis, since
      they do not cover the low molecular mass window. The new direction in proteomic
      research to analyse this "terra incognita" is peptidomics. This novel concept
      aims at the comprehensive visualization and analysis of small polypeptides, thus
      covering the mass range between proteomics and metabonomics. The pacemakers for
      the development of peptidomics technologies are modern mass spectrometry and
      bioinformatics. They are ideally suited for sensitive and comprehensive peptide
      analysis, especially in combination with the massive information content of
      today's genomic and transcriptomic databases. Given the high diversity of native
      peptides in living systems, clinical chemistry and modern medicine are the prime
      application areas. The discovery of relevant peptide biomarkers and drug targets
      will strongly benefit from peptidomics.

PMID- 16464158
TI  - Datamining methodology for LC-MALDI-MS based peptide profiling.
AB  - This report will provide a brief overview of the application of data mining in
      proteomic peptide profiling used for medical biomarker research. Mass
      spectrometry based profiling of peptides and proteins is frequently used to
      distinguish disease from non-disease groups and to monitor and predict drug
      effects. It has the promising potential to enter clinical laboratories as a
      general purpose diagnostic tool. Data mining methodologies support biomedical
      science to manage the vast data sets obtained from these instrumentations. Here
      we will review the typical workflow of peptide profiling, together with typical
      data mining methodology. Mass spectrometric experiments in peptidomics raise
      numerous questions in the fields of signal processing, statistics, experimental
      design and discriminant analysis.

PMID- 16464159
TI  - Prerequisites for peptidomic analysis of blood samples: I. Evaluation of blood
      specimen qualities and determination of technical performance characteristics.
AB  - Proteomics studies aiming at a detailed analysis of proteins, and peptidomics,
      aiming at the analysis of the low molecular weight proteome (peptidome) offer a
      promising approach to discover novel biomarkers valuable for different crucial
      steps in detection, prevention and treatment of disease. Much emphasis has been
      given to the analysis of blood, since this source would by far offer the largest
      number of meaningful biomarker applications. Blood is a complex liquid tissue
      that comprises cells and extra-cellular fluid. The choice of suitable specimen
      collection is crucial to minimize artificial occurring processes during specimen
      collection and preparation (e.g. cell lysis, proteolysis). After specimen
      collection, sample preparation for peptidomics is carried out by physical methods
      (filtration, gel-chromatography, precipitation) which allow for separation based
      on molecular size, with and without immunodepletion of major abundant proteins.
      Differential Peptide Display (DPD) is an offline-coupled combination of Reversed
      Phase-HPLC and MALDI mass spectrometry in combination with in-house developed
      data display and analysis tools. Identifications of peptides are carried out by
      additional mass spectrometric methods (e.g. online LC-ESI-MS/MS). In the work
      presented here, insights into semi-quantitative mass spectrometric profiling of
      plasma peptides by DPD are given. This includes proper specimen selection (plasma
      vs. serum), sample preparation, especially peptide extraction, the determination
      of sensitivity (i.e. by establishing detection limits of exogenously spiked
      peptides), the reproducibility for individual as well as for all peptides
      (Coefficient of Variation calculations) and quantification (correlation between
      signal intensity and concentration). Finally, the implications for clinical
      peptidomics are discussed.

PMID- 16464160
TI  - Prerequisites for peptidomic analysis of blood samples: II. Analysis of human
      plasma after oral glucose challenge -- a proof of concept.
AB  - Mass spectrometric plasma analysis for biomarker discovery has become an
      exploratory focus in proteomic research: the challenges of analyzing plasma
      samples by mass spectrometry have become apparent not only since the human
      proteome organization (HUPO) has put much emphasis on the human plasma proteome.
      This work demonstrates fundamental proteomic research to reveal sensitivity and
      quantification capabilities of our Peptidomics technologies by detecting distinct
      changes in plasma peptide composition in samples after challenging healthy
      volunteers with orally administered glucose. Differential Peptide Display (DPD)
      is a technique for peptidomics studies to compare peptides from distinct
      biological samples. Mass spectrometry (MS) is used as a qualitative and
      quantitative analysis tool without previous trypsin digestion or labeling of the
      samples. Circulating peptides (< 15 kDa) were extracted from 1.3 mL plasma
      samples and the extracts separated by liquid chromatography into 96 fractions.
      Each fraction was subjected to MALDI MS, and mass spectra of all fractions were
      combined resulting in a 2D-display of > 2,000 peptides from each sample.
      Endogenous peptides that responded to oral glucose challenge were detected by DPD
      of pre-and post-challenge plasma samples from 16 healthy volunteers and
      subsequently identified by nESI-qTOF MS. Two of the 15 MS peaks that were
      significantly modulated by glucose challenge were subsequently identified as
      insulin and C-peptide. These results were validated by using immunoassays for
      insulin and C-peptide. This paper serves as a proof of principle for proteomic
      biomarker discovery down to the pM concentration range by using small amounts of
      human plasma.

PMID- 16464162
TI  - Towards characterization of the human urinary peptidome.
AB  - Biomarker discovery in human urine has become an evolving and potentially
      valuable topic in relation to renal function and diseases of the urinary tract.
      In order to deliver on the promises and to facilitate the development of
      validated biomarkers or biomarker panels, protein and peptide profiling
      techniques need high sample throughput, speed of analysis, and reproducibility of
      results. Here, we outline the performance characteristics of the liquid
      chromatography/MALDI-TOF-MS based differential peptide display (DPD(1)) approach
      for separating, detecting, abundance profiling and identification of native
      peptides derived from human urine. The typical complexity of peptides in human
      urine (resolution of the technique with respect to detectable number of
      peptides), the reproducibility (coefficient of variation for abundance profiles
      of all peptides detected in biological samples) and dynamic range of the
      technique as well as the lower limit of detection were characterized. A
      substantial number of peptides present in normal human urine were identified and
      compared to findings in four published proteome studies. In an explorative
      approach, pathological urines from patients suffering from post-renal-filtration
      diseases were qualitatively compared to normal urine. In conclusion, the
      peptidomics technology as shown here has a great potential for high throughput
      and high resolution urine peptide profiling analyses. It is a promising tool to
      study not only renal physiology and pathophysiology and to determine new
      biomarkers of renal diseases; it also has the potential to study remotely
      localized or systemic aberrations within human biology.

PMID- 16464161
TI  - High-throughput biomarker discovery and identification by mass spectrometry.
AB  - Native peptides and proteins are of increasing interest in biomedical research
      because they hold promise to represent a large number of useful diagnostic and
      therapeutic biomarkers. Discovery attempts from patient samples have to deal with
      the complexity of biology from a disease perspective as well as with a high
      individual variability. High throughput screening of samples is therefore the
      strategy of choice to detect relevant peptidic biomarkers, and requires a high
      order of automation particularly in the detection process. In this contribution,
      a novel technical approach employing a fully automated MALDI-TOF/TOF mass
      spectrometer is described. This approach combines high throughput biomarker
      discovery with the identification of corresponding endogenous peptides in one
      instrument and from the same set of samples. The degree of automation allows the
      analysis of thousands of chromatographic fractions corresponding to up to one
      hundred patient samples per day. The applied relative quantification via
      Differential Peptide Display((R)) is performed in a label-free way and shows a
      dynamic range of up to four orders of magnitude in the accessible peptide
      concentrations. The typical limit of detection is in the mid- to low-picomolar
      range for body fluids such as blood plasma, urine and cerebrospinal fluid.
      Sequence assignment via MALDI-TOF/TOF mass spectrometry is carried out either in
      an overview approach, characterizing rapidly the peptide composition e.g. of a
      novel sample, or in a directed approach, analyzing a list of biomarker candidates
      deduced from statistically significant abundance differences from the biomarker
      discovery process.

PMID- 16464164
TI  - Peptidomics biomarker discovery in mouse models of obesity and type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is caused by the failure of the pancreatic beta
      cell to secrete sufficient insulin to compensate a decreased response of
      peripheral tissues to insulin action. The pathological events causing beta-cell
      dysfunctions are only poorly understood and early markers that would predict
      islet function are missing. In contrast to immunoassays, unbiased proteomic
      technologies provide the opportunity to screen for novel marker protein and
      peptides of T2DM. An important subset of the proteome, peptides and peptide
      hormones secreted by the pancreas are deregulated in T2DM. The mass range of
      peptides and small proteins (1-20 kDa) is only sufficiently targeted by
      peptidomics, a combination of liquid chromatographic and mass spectrometric (MS)
      peptide analysis. Here, we describe the application of isotope label-free
      quantitative peptidomics to display and quantify relevant changes in the level of
      pancreatic peptides and peptide hormones in a preclinical model of T2DM, the
      Lep(ob)/Lep(ob) mouse. The amino acid sequence of statistical relevant top
      candidates was determined by MS/MS fragmentation or Edman degradation. The
      comparison of lean versus obese mice revealed increased levels of islet-specific
      peptides that can be divided into the following categories 1) the major islet
      peptide hormones insulin, amylin and glucagon; 2) proinsulin and C-peptide and 3)
      novel processing products of secretogranin, glucagon and amylin. Furthermore, we
      found increased levels of proteins and peptides implicated in zymogen granule
      maturation (syncollin) and nutritional digestion. In summary, our findings
      demonstrate that peptidomics is a valid approach to screen for novel peptide
      biomarkers.

PMID- 16464163
TI  - The concept of functional peptidomics for the discovery of bioactive peptides in
      cell culture models.
AB  - Detection and purification of novel bioactive peptides from biological sources is
      a scientific task that led to a substantial number of important discoveries. One
      major laborious approach used is the repetitive stepwise separation of the test
      sample into several fractions followed by the determination of their bioactivity,
      until purity allows for sequence identification. We tested whether functional
      peptidomics, a combination of biological read-outs with differential peptide
      display (DPD) is a suitable strategy to isolate bioactive peptides at lower
      workload and with improved success. Additionally, we evaluated the use of DPD to
      monitor the processing status of proinsulin by inhibition of the insulin
      processing pathway. The rat insulinoma cell line INS-1 stimulated either with 2
      mmol/l or 10 mmol/l glucose was used as model to generate differential peptide
      displays. In parallel, the bioactivity of the supernatants from the INS-1 cells
      was measured by glucose uptake and lipolysis assays using the adipocyte cell line
      3T3-L1. We were able to quickly and elegantly trace the known activity of insulin
      to increase glucose uptake and inhibit lipolysis. Following re-chromatography of
      selected fractions, relevant peptides were identified by DPD and bioassays: the
      rat insulin-1 precursor and two different insulin peptides. We demonstrated in a
      semi-quantitative fashion that inhibition of proinsulin processing leads to
      accumulation of the insulin precursor, and reduced secretion of insulin-1. Thus,
      we conclude that DPD is an attractive support technology in peptide purification
      strategies aiming to identify bioactive compounds, and is superior to ELISA in
      discriminating between the processing status of insulin and its precursor.

PMID- 16464165
TI  - Identification of Peptide tumor markers in a tumor graft model in immunodeficient
      mice.
AB  - The medical demand for useful biomarkers is large and still increasing. This is
      especially true for cancer, because for this disease adequate diagnostic markers
      with high specificity and sensitivity are still lacking. Despite advances in
      imaging technologies for early detection of cancer, peptidomic multiplex
      techniques evolved in recent years will provide new opportunities for detection
      of low molecular weight (LMW) proteome biomarker (peptides) by mass spectrometry.
      Improvements in peptidomics research were made based on separation of peptides
      and/or proteins by their physico-chemical properties in combination with mass
      spectrometric detection, respectively identification, and sophisticated
      bioinformatic tools for data analysis. To evaluate the potential of serological
      tumor marker detection by differential peptide display (DPD) we analyzed plasma
      samples from a tumor graft model. After subcutaneous injection of HCT-116 cells
      in immunodeficient mice and their growth to a palpable tumor, plasma samples were
      analyzed by DPD. The comparison of obtained mass spectrometric data allows
      discovery of tumor specific peptides which fit well into the biological context
      of cancer pathogenesis and show a strong correlation to tumor growth. The
      identified peptides indicate events associated with hyper-proliferation and
      dedifferentiation of cells from an epithelial origin, which are typical
      characteristics of human carcinomas. We conclude that these findings are a "proof
      of principle" to detect differentially expressed, tumor-related peptides in
      plasma of tumor-bearing mice.

PMID- 16464166
TI  - Peptide sequence prediction supported by correlation-associated networks in human
      cerebrospinal fluid.
AB  - During the course of biosynthesis, processing and degradation of a peptide, many
      structurally related intermediate peptide products are generated. Human body
      fluids and tissues contain several thousand peptides that can be profiled by
      reversed-phase chromatography and subsequent MALDI-ToF-mass spectrometry.
      Correlation-Associated Peptide Networks (CAN) efficiently detect structural and
      biological relations of peptides, based on statistical analysis of peptide
      concentrations. We combined CAN with recognition of probable cleavage sites for
      peptidases and proteases in cerebrospinal fluid, resulting in a model able to
      predict the sequence of unknown peptides with high accuracy. On the basis of this
      approach, identification of peptide coordinates can be prioritized, and a rapid
      overview of the peptide content of a novel sample source can be obtained.

PMID- 16464167
TI  - Identification of novel biomarker candidates by differential peptidomics analysis
      of cerebrospinal fluid in Alzheimer's disease.
AB  - The objective of this work was the application of peptidomics technologies for
      the detection and identification of reliable and robust biomarkers for
      Alzheimer's disease (AD) contributing to facilitate and further improve the
      diagnosis of AD. Using a new method for the comprehensive and comparative
      profiling of peptides, the differential peptide display (DPD), 312 cerebrospinal
      fluid (CSF) samples from AD patients, cognitively unimpaired subjects and from
      patients suffering from other primary dementia disorders were analysed as four
      independent analytical sets. By combination with a cross validation procedure,
      candidates were selected from a total of more than 6,000 different peptide
      signals based on their discriminating power. Twelve candidates were identified
      using mass-spectrometric techniques as fragments of the possibly neuroprotective
      neuroendocrine protein VGF and another one as the complement factor C3 descendent
      C3f. The combination of peptide profiling and cross validation resulted in the
      detection of novel potential biomarkers with remarkable robustness and a close
      relation to AD pathophysiology.

PMID- 16464168
TI  - The future of post-genomic biology at the proteomic level: an outlook.
AB  - Drug discovery and early-stage drugs and biomarkers development is a continuous
      adaptation and maturation process. The cycle of changes based on new findings is
      coupled with shifts in research priorities and make this part of pharmaceutical
      research a challenging endeavour. Over the last years, the emphasis on genomics
      has shifted to proteomics, the science of understanding how proteins translate
      gene information into function, and metabonomics, the science of small
      metabolites that are further apart from genomic projects. Proteomics describes
      the analysis of the protein complement of a biological sample with respect to
      temporal and spatial resolution. This technology is based on separation of
      complex protein mixtures by 2D gel-electrophoresis, in gel digest and mass
      spectrometric analysis of the protein fragments. Proteomics has been recently
      flanked by peptidomics, a new research direction aimed at the comprehensive
      analysis of small (1-20 kDa) polypeptides, thus covering the gap between
      proteomics and metabonomics. The refinement of peptidomics is based on an
      essential paradigm related to modularity and diversity. Peptides are a paramount
      example of how one single gene can release multiple functionalities. We can
      expect fast progress in understanding protein and peptide networks from a systems
      biology approach ending in the discovery of new peptide targets. However, the way
      from a complex sample to potential diagnostic and therapeutic targets will depend
      on technological developments and from the ability to discriminate true disease
      related signals from false positive and negative signals, and the way from target
      discovery to target validation will not be short.

PMID- 16464170
TI  - Role of osteoprotegerin (OPG) in cancer.
AB  - OPG (osteoprotegerin), a secreted member of the TNF (tumour necrosis factor)
      receptor superfamily, has a variety of biological functions which include the
      regulation of bone turnover. OPG is a potent inhibitor of osteoclastic bone
      resorption and has been investigated as a potential therapeutic for the treatment
      of both osteoporosis and tumour-induced bone disease. Indeed, in murine models of
      cancer-induced bone disease, inhibition of osteoclastic activity by OPG was also
      associated with a reduction in tumour burden. The discovery that OPG can bind to
      and inhibit the activity of TRAIL (TNF-related apoptosis-inducing ligand)
      triggered extensive research into the potential role of OPG in the regulation of
      tumour cell survival. A number of reports from studies using in vitro models have
      shown that OPG protects tumour cells from the effects of TRAIL, thereby possibly
      providing tumour cells that produce OPG with a survival advantage. However, the
      ability of OPG to act as a tumour cell survival factor remains to be verified
      using appropriate in vivo systems. A third area of interest has been the use of
      OPG as a prognostic marker in various cancer types, including myeloma, breast and
      prostate cancer. This review provides an overview of the role of OPG in cancer,
      both in cancer-induced bone disease and in tumour growth and survival.

PMID- 16464169
TI  - Adiponectin: a key adipocytokine in metabolic syndrome.
AB  - The metabolic syndrome, a cluster of metabolic disorders often associated with
      visceral obesity, increases cardiovascular mortality and morbidity. As the body's
      largest endocrine organ, adipose tissue not only stores excess body energy, but
      also secretes a variety of bioactive adipocytokines. Obese patients, particularly
      those with visceral fat accumulation, have reduced plasma levels of adiponectin,
      the most abundant and adipose-specific adipocytokine. Although the association of
      adiponectin with several diseases remains controversial, many clinical studies
      have demonstrated that low plasma concentrations of adiponectin
      (hypoadiponectinaemia) associate closely with obesity-related diseases, including
      atherosclerotic cardiovascular diseases, Type II diabetes mellitus, hypertension
      and dyslipidaemia. Accumulating experimental evidence indicates that adiponectin
      possesses anti-atherogenic, anti-inflammatory and anti-diabetic properties and
      may also participate importantly in the mechanism of metabolic syndrome and other
      diseases. Despite these associations, further clinical and experimental
      investigations will be needed to illuminate the in vivo pathophysiological
      significance of this protein. Although evaluation of adiponectin as a novel
      therapy will ultimately require clinical intervention studies, this mediator may
      represent a novel target for the prevention and treatment of visceral obesity
      metabolic syndrome.

PMID- 16464171
TI  - Granulocyte apoptosis in the pathogenesis and resolution of lung disease.
AB  - Apoptosis, programmed cell death, of neutrophil and eosinophil granulocytes is a
      potential control point in the physiological resolution of innate immune
      responses. There is also increasing evidence that cellular processes of apoptosis
      can be dysregulated by pathogens as a mechanism of immune evasion and that
      delayed apoptosis, resulting in prolonged inflammatory cell survival, is
      important in persistence of tissue inflammation. The identification of cell-type
      specific pathways to apoptosis may allow the design of novel anti-inflammatory
      therapies or agents to augment the innate immune responses to infection. This
      review will explore the physiological roles of granulocyte apoptosis and their
      importance in infectious and non-infectious lung disease.

PMID- 16464172
TI  - Immune responses to Helicobacter pylori colonization: mechanisms and clinical
      outcomes.
AB  - Helicobacter pylori colonizes the stomachs of half of the world's population and
      usually persists in the gastric mucosa of human hosts for decades or life.
      Although most H. pylori-positive people are asymptomatic, the presence of H.
      pylori is associated with increased risk for the development of peptic ulcer
      disease, gastric adenocarcinoma and gastric lymphoma. The development of a
      sustained gastric inflammatory and immune response to infection appears to be
      pivotal for the development of disease. During its long co-existence with humans,
      H. pylori has evolved complex strategies to maintain a mild inflammation of the
      gastric epithelium while limiting the extent of immune effector activity. In this
      review, the nature of the host immune response to H. pylori infection and the
      mechanism employed by the bacterium to evade them is considered. Understanding
      the mechanisms of colonization, persistence and virulence factors of the
      bacterium as well as the innate and adaptive immune responses of the host are
      critically important for the development of new strategies to prevent the
      development of H. pylori-induced gastroduodenal disease.

PMID- 16464173
TI  - Molecular genetics of human hypertension.
AB  - EH (essential hypertension) is a major public health problem in many countries
      due to its high prevalence and its association with coronary heart disease,
      stroke, renal disease, peripheral vascular disease and other disorders.
      Epidemiological studies have demonstrated that EH is heritable. Owing to the fact
      that blood pressure is controlled by cardiac output and total peripheral
      resistance, many molecular pathways are believed to be involved in the disease.
      In this review, recent genetic studies investigating the molecular basis of EH,
      including different molecular pathways, will be highlighted.

PMID- 16464174
TI  - Transcriptional stimulation of the human NHE3 promoter activity by PMA: PKC
      independence and involvement of the transcription factor EGR-1.
AB  - NHE3 (Na+/H+ exchanger 3) is essential for Na+ absorption in the ileum and is
      expressed in a cell-specific manner in the apical membrane of the intestinal
      epithelial cells. In the present study, we report the stimulatory effect of PMA
      on the hNHE3 (human NHE3) transcription. Pretreatment with actinomycin D or
      cycloheximide blocked the up-regulation of the NHE3 mRNA by PMA, indicating that
      the increased level of NHE3 mRNA expression is regulated by transcriptional
      activation and is dependent on de novo protein synthesis. 5'-Deletion of the
      promoter region and transfection analysis in C2BBe1 cells revealed that the PMA
      effect is mediated through a GC-rich DNA region between nt -88 and -69. Gel
      mobility-shift assays demonstrated that in nuclear extracts from C2BBe1 cells
      grown under the basal growth conditions, Sp1 (stimulating protein-1) and Sp3
      interact with this GC-rich DNA region, while, in PMA-treated nuclear extracts,
      PMA-induced EGR-1 (early growth response gene product 1) transcription factor
      binds to the same site. Binding of EGR-1 diminished the Sp1 and Sp3 interactions
      with this promoter region significantly. Co-transfection of Sp1 or Sp3 into SL2
      cells activated the NHE3-reporter constructs, suggesting that Sp1 and Sp3 act as
      positive regulators of the NHE3 expression. In addition, overexpression of EGR-1
      was sufficient to transactivate the NHE3-reporter gene activity, and knockdown of
      EGR-1 with gene-specific small interfering RNA resulted in inhibition of the PMA
      induced up-regulation of the endogenous NHE3 mRNA expression. Furthermore, the
      PKC (protein kinase C) inhibitor chelerythrine chloride did not affect PMA
      induced NHE3 promoter activity, suggesting that PMA stimulation of the hNHE3 gene
      expression may be PKC-independent.

PMID- 16464177
TI  - Evaluation of therapeutic strategies: a new method for balancing risk and
      benefit.
AB  - OBJECTIVE: A patient-specific drug safety-efficacy index was developed that
      combined objective clinical trial information about dose-related efficacy and
      toxicity with subjective perspectives on efficacy-toxicity trades. METHODS:
      Patient preferences were systematically assessed using the probability tradeoff
      technique (PTT). Toxicity ranges over which a drug's efficacy exceeded the
      patient's minimally acceptable efficacy represented ranges of "surplus efficacy."
      These can be related to the dose interval in which a drug delivers this surplus
      efficacy. Seventy surplus efficacy functions (for 7 hypothetical drugs and 10
      hypothetical preference curves) were simulated. RESULTS: The analysis showed that
      index values change markedly by dose and patient preference, suggesting that
      different patients will benefit from different drugs depending on the dose
      prescribed and each patient's subjective assessment of the efficacy/toxicity
      tradeoff. In most situations, drugs achieve positive surplus efficacy only over
      limited dose ranges. The model was sensitive to different preference curves and
      discriminated well among drugs with different efficacy or safety profiles.
      CONCLUSION: This index provides a new, systematic approach to choosing a specific
      therapeutic intervention and dosage, when known risks and benefits are reconciled
      against patient-specific preferences among an array of therapeutic alternatives.

PMID- 16464176
TI  - A 1-year cost-effectiveness model for the treatment of chronic schizophrenia with
      acute exacerbations in Belgium.
AB  - OBJECTIVE: A 1-year semi-Markov model was constructed to simulate the cost
      effectiveness of atypical and typical antipsychotic treatments for schizophrenia.
      METHODS: The core model comprised nine 6-week cycles and includes events such as
      survival, response, adverse events, and compliance. The nature, duration,
      intensity, and timing of adverse events were incorporated. Compliance was modeled
      as a function of health state, time, and adverse events. Three first-line
      treatments were considered (risperidone, olanzapine, and haloperidol oral) and
      the transition probabilities of switching between five different therapies
      (haloperidol oral, haloperidol depot, risperidone, olanzapine and clozapine) were
      included. Effectiveness was modeled based on a modified method of TWiST (time
      without symptoms and toxicity). The direct costs of utilization of medical
      resources are taken into account, including five different patient care settings,
      consultations, neuroleptic medication, laboratory tests, and treatment of side
      effects. RESULTS: This paper reports the methodology used to construct the model
      and the results obtained when it was applied to the treatment of patients with
      schizophrenia in the Belgian health care system. CONCLUSIONS: Over the study
      period, risperidone and olanzapine were more cost-effective than haloperidol and
      of the two major atypical drugs, risperidone was the more cost-effective.

PMID- 16464175
TI  - Subcellular translocation signals regulate Geminin activity during embryonic
      development.
AB  - BACKGROUND INFORMATION: Geminin (Gem) is a protein with roles in regulating both
      the fidelity of DNA replication and cell fate during embryonic development. The
      distribution of Gem is predominantly nuclear in cells undergoing the cell cycle.
      Previous studies have demonstrated that Gem performs multiple activities in the
      nucleus and that regulation of Gem activation requires nuclear import in at least
      one context. In the present study, we defined structural and mechanistic features
      underlying subcellular localization of Gem and tested whether regulation of the
      subcellular localization of Gem has an impact on its activity in cell fate
      specification during embryonic development. RESULTS: We determined that nuclear
      localization of Gem is dependent on a bipartite NLS (nuclear localization signal)
      in the N-terminus of Xenopus Gem protein. This bipartite motif mapped to a Gem N
      terminal region previously shown to regulate neural cell fate acquisition.
      Microinjection into Xenopus embryos demonstrated that import-deficient Gem was
      incapable of modulating ectodermal cell fate, but that this activity was rescued
      by fusion to a heterologous NLS. Cross-species comparison of Gem protein
      sequences revealed that the Xenopus bipartite signal is conserved in many non
      mammalian vertebrates, but not in mammalian species assessed. Instead, we found
      that human Gem employs an alternative N-terminal motif to regulate the protein's
      nuclear localization. Finally, we found that additional mechanisms contributed to
      regulating the subcellular localization of Gem. These included a link to Crm1
      dependent nuclear export and the observation that Cdt1, a protein in the pre
      replication complex, could also mediate nuclear import of Gem. CONCLUSIONS: We
      have defined new structural and regulatory features of Gem, and showed that the
      activity of Gem in regulating cell fate, in addition to its cell-cycle-regulatory
      activity, requires control of its subcellular localization. Our data suggest that
      rather than being constitutively nuclear, Gem may undergo nucleocytoplasmic
      shuttling through several mechanisms involving distinct protein motifs. The use
      of multiple mechanisms for modulating Gem subcellular localization is congruent
      with observations that Gem levels and activity must be stringently controlled
      during cell-cycle progression and embryonic development.

PMID- 16464179
TI  - Economic evaluation of letrozole in the treatment of advanced breast cancer in
      postmenopausal women in Canada.
AB  - OBJECTIVE: To determine the cost-effectiveness of initiation of second-line
      hormone therapy with letrozole in the treatment of advanced breast cancer in
      postmenopausal women in Canada, compared to megestrol acetate. METHODS: A
      modified Markov model, incorporating seven health states, was designed to
      simulate the treatment of patients with advanced breast cancer from second-line
      hormone therapy to death. The model was constructed with data from a clinical
      trial, literature sources, and interviews with breast cancer treatment experts.
      Canadian experts provided information on resource utilization patterns and local
      costs were attached to these resources. The model was used to calculate mean
      survival time, time without progression, and total direct medical costs for
      patients initiating treatment with letrozole 2.5 mg or megestrol acetate 160 mg.
      RESULTS: The mean survival time and time without progression for letrozole 2.5 mg
      patients were 28.3 months and 19.0 months, respectively, compared to 25.7 months
      and 16.5 months for megestrol acetate 160 mg patients. Total treatment costs for
      both groups were similar with the letrozole 2.5 mg group costing dollar 20,068
      per patient, dollar 1061 more than the megestrol acetate 160 mg group (dollar
      CAN, 1996). The cost-effectiveness ratio for letrozole 2.5 mg with respect to
      megestrol was dollar 5051 per year of life gained. Sensitivity analysis showed
      that this ratio was sensitive to variations in the probabilities governing
      disease progression. CONCLUSIONS: Advanced breast cancer patients initiating
      second-line hormone therapy with letrozole 2.5 mg have better clinical outcomes
      than patients receiving megestrol acetate 160 mg. Furthermore, this benefit comes
      at an acceptable cost to the Canadian health care system.

PMID- 16464178
TI  - Estimates of the lifetime direct costs of treatment for metastatic breast cancer.
AB  - OBJECTIVE: Breast cancer remains the highest incident cancer among females in the
      United States and previous research suggests that a considerable portion of
      patients will eventually progress to the metastatic phase of the disease. This
      paper provides the first estimate of the lifetime direct costs of treating
      metastatic disease for one annual diagnostic cohort of breast cancer patients.
      METHODS: Incidence rates were combined with US population counts to estimate the
      number of breast cancer cases diagnosed in 1994. Estimates of progression to
      metastatic disease (from Canadian provincial cancer registry data), costs of care
      (derived from patients' claims histories), survival (from SEER data), and
      national mortality rates (from US Census Bureau) were integrated, using
      Statistics Canada's Population Health Model (POHEM) to calculate lifetime costs.
      RESULTS: This study estimates that more than 40% of the women diagnosed with
      breast cancer will progress to metastatic disease. On average, women with
      metastatic disease are expected to live 3 years and to incur direct treatment
      costs of approximately dollar 60,000 per case, resulting in a total lifetime cost
      for the cohort of almost dollar 4.2 billion. CONCLUSIONS: The high rate of
      recurrence of breast cancer argues for the development of interventions that can
      prevent or delay the onset of metastatic disease. These estimates of lifetime
      costs and the methodology on which they are based can be used to evaluate the
      cost-effectiveness of such secondary prevention strategies. These estimates also
      can serve as a benchmark against which the lifetime costs of treating other
      diseases can be assessed.

PMID- 16464180
TI  - Economic assessment of a maintenance treatment strategy in prevention of
      recurrent depressive disorder.
AB  - OBJECTIVE: To compare the 12-month cost-effectiveness of milnacipran in
      maintenance treatment of depression to that of medical follow-up without
      antidepressant. METHOD: A Markov model with transition probabilities from a
      double blind clinical trial demonstrating the prophylactic efficacy of
      milnacipran was used. Other parameters were obtained from published sources.
      RESULTS: Base-case incremental cost for preventive treatment was 1,191 FF. It was
      reduced to 685 FF when using a 25% hospitalization rate in case of recurrence.
      Patients with a high initial response had extra cost of 191 FF and cost-utility
      was estimated to be 23,875 FF per QALY gained. For those patients, using a 25%
      hospitalization rate in case of recurrence, costs were lower at 1,174 FF and
      preventive strategy was dominating. CONCLUSION: Cost of maintenance therapy is
      partially balanced by the gain from recurrence prevention. It should be focused
      on patients with few residual symptoms or a high probability of hospitalization
      in case of recurrence.

PMID- 16464182
TI  - Commentary: pharmacoeconomics and outcomes research: expanding the healthcare
      "outcomes" market.

PMID- 16464183
TI  - Modeling the use of triple combination therapy in five countries: nevirapine,
      Zidovudine, and Didanosine.
AB  - OBJECTIVE: In this study, we modify previously published models to estimate the
      short- and long-term consequences of nevirapine triple combination therapy use in
      five developed countries. Current pharmacoeconomic practice requires the de novo
      model development for each new therapy comparison. This approach is lengthy and
      costly, and it may yield models with very different structures. Standardized,
      detailed disclosure of model assumptions and parameters makes it possible to
      recycle published models with minor structural modifications to examine the
      efficiency of therapies based on new trial data. METHODS: Two well-publicized
      models of HIV therapy are modified to fit new trial data comparing double and
      triple combination therapy with nevirapine; model parameters are adjusted to
      represent clinical practice and cost structure in five countries. A short-term
      model uses trial data from advanced-stage patients to estimate first-year costs
      and consequences. A long-term model uses data from antiretroviral-naive patients
      to estimate long-term cost-effectiveness. RESULTS: During the first year, for
      each 100 individuals treated with nevirapine triple combination therapy, 2.7
      deaths and 30.8-31.4 opportunistic disease events would be averted compared to
      employing dual therapy. Additionally, 61% to 142% of the first-year costs of
      nevirapine therapy would be offset by other medical care costs savings [FF19,749,
      DM3,778, 3334 (x1000) lire, 293 (x1000) ptas, and US $3,569]. Compared to dual
      combination therapy, nevirapine triple combination therapy is predicted to yield
      incremental cost-effectiveness ratios (discounted at 3%) of FF101,057, DM30,709,
      28,066 (x1000) lire, 1294 (x1000) ptas, and US $14,338. CONCLUSION: Published,
      well-constructed, and documented cost-effectiveness models can be reused to
      estimate the economic impact of therapies for HIV disease. Such models can also
      be used to provide insight into the factors that affect efficiency across
      countries. Our use of clinical trial data on nevirapine, together with published
      HIV economic models, provides support for the hypothesis that nevirapine is cost
      effective under the cost structures of five developed countries.

PMID- 16464184
TI  - SF-36 as a predictor of health states.
AB  - BACKGROUND: There are a number of claims that Medical Outcomes Study Short Form
      36 (MOS SF-36) mean scores can be used to discriminate between healthy and
      nonhealthy persons and determine various levels of health. OBJECTIVES: The
      purpose of this study was to evaluate the ability of the SF-36 to predict whether
      or not respondents reported health problems. METHODS: We used structural equation
      modeling (SEM) techniques to evaluate the SF-36 and its ability to discriminate
      between those who reported health problems or reported physician-determined
      illness and those who did not in a sample from the 1990 National Survey of
      Functional Health Status (NHS). RESULTS: The correlation between physician
      determined illness and Physical Health was -.404, resulting in 16.32% shared
      variance. The correlation between reported health problems and Physical Health
      was -.360, resulting in 12.96% shared variance. These correlations are markedly
      lower than those to the eight first-order scales or between Physical and Mental
      Health (r = .889). Mental Health could not predict physician-determined illness
      or reported health problems independent of Physical Health. CONCLUSIONS: The SF
      36 is relatively poor at accounting for the health status of respondents. There
      are significant paths but the variance accounted for in absolute and relative
      terms is small. Physical Health does a much better job of accounting for general
      mental health than it does for perceived health problems or physician-determined
      illness. These findings suggest that the SF-36 may not discriminate well between
      healthy and nonhealthy groups and that objective measures of health status may be
      required in conjunction with the use of the SF-36.

PMID- 16464185
TI  - Comparing SSRI treatment costs for depression using retrospective claims data:
      the role of nonrandom selection and skewed data.
AB  - BACKGROUND AND OBJECTIVES: Since conventional randomized clinical trials often do
      not reflect the real world circumstances of prescribing behavior and patient
      outcomes, the use of retrospective administrative claims databases (RACD) has
      become more common in treatment cost comparisons among alternative pharmaceutical
      compounds. Several recent RACD studies have compared treatment costs for
      depressed patients prescribed SSRIs such as fluoxetine, sertraline and
      paroxetine. These cost comparisons have reached mixed conclusions. To begin to
      explain and reconcile the mixed SSRI cost comparison evidence, we undertake a
      variety of alternative multivariate analyses using a publicly available RACD.
      METHODS AND DATA: The 1995 to 1996 data encompasses a time period when all three
      SSRIs had become well-established agents. We report and compare results from
      multivariate linear regressions, logistic regressions, ordered probits and sample
      selectivity models, and examine robustness when adjustments are made for outlier
      observations and skewed distributions. RESULTS AND CONCLUSIONS: While choice of
      initial SSRI is nonrandom, the effect of sample selectivity on total depression
      related and total health care expenditure is neutral across SSRIs. Although most
      cost measures are numerically greatest for fluoxetine, depression-related
      outpatient and hospitalization costs do not significantly differ by choice of
      initial SSRI. These findings are robust to alternative assumptions,
      specifications, and procedures. Antidepressant medication costs, however, are
      significantly higher when fluoxetine is the initial SSRI rather than sertraline
      or paroxetine, reflecting the larger proportion of fluoxetine patients prescribed
      a daily dosage of two or more capsules. Both total depression-related and total
      health care log-transformed costs are significantly lower for sertraline than
      fluoxetine.

PMID- 16464187
TI  - Designing naturalistic prospective studies of economic and effectiveness outcomes
      associated with novel antipsychotic therapies.
AB  - The cornerstone of recent pharmacoeconomic work in schizophrenia is the
      hypothesis that the improved efficacy of novel antipsychotic medications will
      lead to a reduction in medical services utilization, thereby reducing direct
      medical costs associated with treatment. Creating the most valid design to
      prospectively examine the effectiveness and costs of competing pharmacotherapies
      requires a dialectic of opposing research paradigms. The final protocol must
      represent a series of decisions that strike a careful balance between being
      scientifically sound (internal validity) and generalizable to the real world of
      clinical treatment (external validity). The results must be useful to decision
      makers in determining to what extent reductions in healthcare expenditures can
      offset higher drug acquisition costs within their type of treatment environment.
      This article is a review of several methodological challenges in the design of
      medical effectiveness trials, including whether to blind the study, definition of
      the patient population, degree of physician discretion in treatment, and how to
      collect and analyze data for patients who discontinue their originally assigned
      medication. The article also provides a discussion of how clinical practices can
      inform decisions made to meet these challenges. The issues are illustrated
      through a prospective study designed to evaluate the cost-effectiveness of the
      newer antipsychotics in general and olanzapine in particular. Cost-effectiveness
      studies of novel antipsychotic medications, particularly those with naturalistic
      designs, will increase in importance as the use of these second-generation agents
      continues to expand.

PMID- 16464186
TI  - The use of conventional antipsychotic medications for patients with schizophrenia
      in a medicaid population: therapeutic and cost outcomes over 2 years.
AB  - OBJECTIVE: To evaluate the association between drug therapy patterns achieved
      with conventional antipsychotics and direct healthcare costs over 2 years.
      METHODS: Paid claims data from the California Medicaid (Medi-Cal) program were
      used to identify 2476 patients with schizophrenia for whom 2 years of data were
      available. Ordinary least squares (OLS) regression models were used to estimate
      the association between lack of antipsychotic drug therapy, delayed therapy,
      changes in medications, and continuous therapy on healthcare costs over a 2-year
      period. RESULTS: Nearly 99% of Medi-Cal patients with schizophrenia were treated
      with conventional antipsychotics. Patients with schizophrenia consumed nearly
      $48,000 in direct costs over 2 years. Over 16% of patients did not use any
      antipsychotic medication for 2 years. Untreated patients used more healthcare
      resources than treated patients did ($10,833, P = .0422), especially psychiatric
      hospital care ($8,027, P = .0004). However, treated patients frequently
      experienced suboptimal drug use patterns. Nearly 33% of treated patients delayed
      antipsychotic therapy for up to 2 years. Delayed therapy was associated with
      increased costs of $12,285 (P = .070). Over 56% of patients experienced changes
      in therapy that were associated with higher total direct costs ($17,644, P <
      .0001). Finally, only 3.2% of treated patients used an antipsychotic medication
      consistently for 2 years. However, continuous drug therapy was not associated
      with lower costs. CONCLUSION: Suboptimal drug use patterns are common and costly
      in Medi-Cal patients with schizophrenia who initiated therapy with conventional
      antipsychotics.

PMID- 16464188
TI  - The direct cost of rheumatoid arthritis.
AB  - OBJECTIVES: This analysis estimated the direct cost of rheumatoid arthritis (RA)
      from a societal perspective. METHODS: Primary and secondary data sets were used
      to determine the rate of medical resource utilization. National average Medicare
      or Medicaid reimbursement rates were used to value direct costs (in 1994
      dollars). RESULTS: Persons with RA have, on average, dollar 1702 in direct costs
      for treating RA annually. More than half of the total cost is for medications.
      Nursing home care accounts for nearly one fifth of the cost and hospitalizations
      and ambulatory care (combined) comprise another fifth of the total cost. Travel
      to medical appointments and medical supplies make up the remaining 10%. The
      projected annual US direct costs are dollar 3.6 billion for treating RA.
      CONCLUSIONS: The health care utilization in persons with RA is frequent and
      includes a number of components leading to high annual direct cost.

PMID- 16464189
TI  - Clinical and economic outcomes of coronary angioplasty alone or in combination
      with stents in academic health centers: a retrospective database analysis.
AB  - OBJECTIVES: Indications for the use of stents are evolving and their optimal
      place in therapy remains to be defined. The objective was to compare the 1-year
      clinical and economic outcomes of percutaneous transluminal coronary agioplasty
      (PTCA) with and without the use of stents. METHODS: This retrospective database
      analysis was conducted using data from 60 US academic medical centers in 1996 and
      1997. Outcomes of interest included in-hospital mortality (both on sentinel and
      readmission visits), readmission rates, revascularization procedures, length of
      stay, and the cost of sentinel and readmission hospitalization. RESULTS: A total
      of 27,020 patients either did (n = 13,254) or did not (n = 13,766) receive
      coronary stents in conjunction with PTCA. The median cost of hospitalization for
      the stent group was about dollar 1,409 higher (mean, dollar 1,200) than the no
      stent group and the length of stay was similar (4.3 days vs. 4.5 days,
      respectively, P = .2628). Mortality rates on readmission (0.9% stent vs. 0.8% no
      stent, P = NS) did not differ. However, patients in the stent group had better
      mortality rates compared to the no-stent group during the sentinel visit (1.7%
      vs. 2.7%, P < .001). Stent use was not associated with a significantly lower risk
      of a revascularization procedure on readmission to the same institution (OR 0.95,
      95% CI 0.87-1.04, P = .28). CONCLUSIONS: Stents were associated with a 1%
      decrease of inpatient mortality during the sentinel visit without impacting
      length of stay or readmission rates. This advantage was associated with a dollar
      1,409 higher median cost of hospitalization in the stent group.

PMID- 16464190
TI  - The reliability and validity of the impact on lifestyle questionnaire in patients
      with acromegaly.
AB  - OBJECTIVES: Treatments for acromegaly, a growth hormone disorder, can be
      burdensome to patients, often requiring multiple self-administered injections
      daily. We developed the Impact on Lifestyle Questionnaire (ILQ) to measure the
      impact on patient's lifestyle imposed by the burden of injectable treatments for
      acromegaly. The primary objective of this study was to establish the reliability
      and validity of the ILQ. METHODS: The ILQ consists of the SF-12 and 30 additional
      questions. Thirty-four patients, from two sites, completed the ILQ and scales
      measuring related concepts. Fourteen patients also completed a retest survey 4
      weeks later. Survey sample data were combined with ILQ data from another 56
      patients with acromegaly for a factor analysis. Reliability was assessed with
      Cronbach's alpha and test-retest. Zero-order correlations were examined between
      ILQ subscales and symptoms, depression, SF-12 mental and physical components, a
      measure of self-care burden, appraisal of illness, and single-item measures of
      quality of life and satisfaction. RESULTS: The preconceived subscale structure
      was supported by factor analysis. These factors were internally consistent and
      stable over time. Good convergent validity was demonstrated between the Burden
      and Disruption scales with other measures of the burden of treatment. Patients
      indicated that they were generally compliant with therapy, and that treatment was
      not particularly burdensome or disruptive. Results based on the ILQ were
      consistent with other scales and qualitative responses. CONCLUSIONS: The ILQ has
      three subscales, Burden, Lifestyle Disruption, and Compliance, that are reliable
      and demonstrate preliminary evidence of construct validity.

PMID- 16464191
TI  - How do Italian pharmacoeconomists evaluate indirect costs?
AB  - OBJECTIVES: To investigate how indirect costs are evaluated in pharmacoeconomic
      studies in Italy and the attitude of Italian pharmacoeconomists toward indirect
      costs. METHODS: A literature review was conducted, specifically focused on
      pharmacoeconomic studies including indirect costs carried out in Italy, and a
      suevey among Italian pharmacoeconomics experts. RESULTS: Nineteen studies were
      available for review. Although the methods used to calculate the value of
      production loss due to morbidity were all based on the Human Capital Approach
      (HCA), there was a wide variability among studies in practical methods. The
      parameters used to value production losses varied widely too. Of the 25 survey
      responders, 20 considered it important to include indirect costs in
      pharmacoeconomic studies; 56% of those interviewed stated that health authorities
      should require indirect cost evaluations. Most of these experts would include
      indirect cost estimates in drug-pricing calculation. CONCLUSIONS: In Italy
      studies evaluating indirect costs are still only few, although there is evidence
      of an increase. Italian pharmacoeconomists are far from reaching any consensus on
      methods for evaluating these costs. Methods need to be standardized particularly
      with respect to the parameters used to quantify productive time lost in monetary
      terms.

PMID- 16464192
TI  - Data collection methods in prospective economic evaluations: how accurate are the
      results?
AB  - OBJECTIVES: Often in economic evaluations a division is made between those
      studies that have a high level of accuracy versus those that are easily
      generalized. This interstudy dichotomy is often translated into prospective,
      randomized controlled trials with high internal validity and observational and
      modeling studies with a high level of external validity. This article challenges
      this conventional view and examines intrastudy effects on validity. METHOD: A
      review and summary of the literature was conducted in order to assess the impact
      that data collection strategies will have on internal validity. Two scenario
      models were created in order to gain a preliminary understanding of the magnitude
      of the problem. RESULTS: Data collection strategies have an impact on the level
      of internal validity found in an economic evaluation. Comparisons of studies that
      are prospective in nature is misleading as data collection strategy can lead to
      different resource and cost estimates even when all other relevant factors are
      similar. It is possible to shift and improve the level of validity by combining
      different collection methods. CONCLUSIONS: Instead of viewing internal and
      external validity as polar opposites, validity should be considered in terms of a
      continuum within a particular study. The use of proxies to collect resource
      utilization estimates, the reliance on patient self-reported data, and the method
      of collecting this type of data all impact the validity of study results.
      National guidelines for the economic evaluation of agents and devices should
      consider this issue in more depth, and existing evidence rankings should be
      adapted to be more appropriate to pharmacoeconomic studies.

PMID- 16464193
TI  - Meeting the NICE requirements: a Markov model approach.
AB  - The National Institute of Clinical Excellence (NICE) was established in the
      United Kingdom in April 1999 to issue guidance for the National Health Service
      (NHS) on the use of selective new health care interventions. This article
      describes the NICE requirements for both incidence-based cost-effectiveness
      analyses and prevalence-based estimates of the aggregate NHS impact of the new
      drug. The article demonstrates how both of these requirements can be met using
      Markov modeling techniques. A Markov model for a hypothetical new treatment for
      HIV infection is used as an illustration of how to generate the estimates that
      are required by NICE. The article concludes with a discussion of the difficulties
      of obtaining data of sufficient quality to include in the Markov model to ensure
      that the submission meets all the NICE requirements and is credible to the NICE
      advisory board.

PMID- 16464197
TI  - Deep vein thrombosis: cost-effective management of a major health problem.

PMID- 16464198
TI  - Economic evaluation of enoxaparin vs. placebo for the prevention of venous
      thromboembolism in acutely ill medical patients.
AB  - OBJECTIVES: This paper presents an economic evaluation of a strategy of
      thromboprophylaxis in acutely ill medical patients with enoxaparin 40 mg vs. no
      intervention in the context of the French Health System. METHODS: The evaluation
      used a decision-analysis model to simulate the results of a hypothetical
      naturalistic, long-term study reflecting the usual care pattern for the patients.
      The short-term outcomes were derived from an international, double-blind, placebo
      controlled randomized clinical study performed in 1102 patients older than 40
      years. Treatment was scheduled to last 10 +/- 4 days and primary outcome was
      venous thromboembolism events rates between days 1 and 14 assessed clinically or
      through systematic contrast venography. RESULTS: For an hypothetical cohort of
      1000 hospitalized medical patients, the model suggested that the prophylaxis
      strategy would avoid between 1 and 10 deaths (median 4) and between 60 and 127
      cases of venous thromboembolism events (median 94). By including or not the costs
      associated with long-term complications (post-phlebitis syndrome), the net extra
      cost per patient was estimated as a net saving or 35,857 Euros (Euro),
      respectively. The corresponding cost-effectiveness ratios in terms of cost per
      avoided death were a net saving or Euro 8102 (median value), respectively.
      CONCLUSIONS: Thromboprophylaxis with enoxaparin in hospitalized acutely ill
      patients over 40 years of age appears to be an efficient strategy using French
      cost data.

PMID- 16464199
TI  - Economic evaluation of enoxaparin as postdischarge prophylaxis for deep vein
      thrombosis (DVT) in elective hip surgery.
AB  - OBJECTIVES: Clinical trials indicate enoxaparin thromboprophylaxis (Clexane) can
      be effective and safe when used in an outpatient setting and that extending the
      length of thromboprophylaxis with enoxaparin to the postdischarge period may be
      more effective than inpatient thromboprophylaxis alone. This may increase the
      cost of thromboprophylaxis. The objective of the study was to estimate the
      expected cost-effectiveness of using enoxaparin for hospital admission only vs.
      enoxaparin for hospital admission and for 21 days postdischarge. METHODS:
      Decision analysis was used to combine probability, resource use and unit cost
      data, using the framework of cost-effectiveness analysis. The model used a
      societal perspective to estimate the expected costs of treatment and outcomes to
      patients undergoing orthopedic surgery for elective hip replacement. Incremental
      cost-effectiveness ratios were calculated to provide estimates of the cost per
      life gained, cost per year life year gained and cost per quality-adjusted life
      year gained with extended use of enoxaparin thromboprophylaxis. RESULTS: There
      was an expected cost per quality-adjusted life year gained of pounds 5732
      associated with extended enoxaparin thromboprophylaxis. The results were
      sensitive to the percentage of patients who could administer enoxaparin
      injections at home, the rate of DVT associated with standard enoxaparin
      thromboprophylaxis and the rate of PE associated with standard and extended
      enoxaparin thromboprophylaxis. CONCLUSIONS: The analyses indicated that in most
      cases extended enoxaparin thromboprophylaxis resulted in increased costs for
      health care services. In all cases, extended thromboprophylaxis with enoxaparin
      was associated with improved survival and life-years gained.

PMID- 16464200
TI  - Second line pharmacological management of paroxysmal and persistent atrial
      fibrillation in france: a cost analysis.
AB  - OBJECTIVES: Despite optimal pharmacological treatment a large proportion of
      patients with atrial fibrillation (Afib) are not arrhythmia-free, and remain at
      risk for complications such as stroke and cardiac morbidity. If first-line
      treatment fails, most patients receive second-line pharmacological treatment. The
      emergence of new technologies aimed at restoring and maintaining sinus rhythm,
      such as catheter ablation techniques, has increased the interest in the economic
      aspects of second-line pharmacological treatment. The objective was therefore to
      calculate the 5-year direct medical costs of second-line pharmacological
      management of paroxysmal and persistent Afib in France. METHODS: The analysis was
      based on clinical and economic literature and the input of cardiologists
      electrophysiologists. The analysis included probabilities of stroke, sudden
      cardiac death, other cardiac and noncardiac death, direct medical costs of drugs,
      follow-up and complications from the healthcare payer's perspective. Included
      treatment strategies were (1) rhythm control with class Ic and III
      antiarrhythmics and (2) rate control, consisting of digoxin combined with a beta
      blocker or calcium antagonist. Both strategies included aspirin or
      anticoagulation therapy. RESULTS: The average total 5-year cost of Afib was
      16,539 Euro (FF 108,486) per patient. The result was stable to sensitivity
      analysis on incidence of stroke and type of stroke prevention. The main cost
      drivers were follow-up visits and hospitalizations and the cost of congestive
      heart failure. Both items being subject to some variation, they were submitted to
      sensitivity analysis showing minimal 5-year costs still over 14,483 Euro (FF
      95,000). CONCLUSIONS: Afib management places high demands on medical resources
      mainly through its complications and comorbidity.

PMID- 16464201
TI  - Predictors of long-term persistence on statins in a subsidized clinical
      population.
AB  - OBJECTIVES: The use of statins in primary prevention of cardiovascular disease is
      currently under debate. This study characterizes and identifies predictors of the
      persistence of use of statins in a clinical cohort of subsidized new users of
      similar age to the WOSCOPS trial subjects. METHODS: Medical, pharmaceutical, and
      demographic records for the period January 1, 1987 through December 31, 1994 were
      extracted from the databases of Quebec's provincial health plan for a 10% random
      sample of social assistance recipients. Patients remained eligible for inclusion
      if they had received a first dispensation of a statin between January 1, 1987 and
      July 31, 1994. Persistence was defined as the number of days on treatment with a
      statin while continuing to renew dispensations within a defined time limit.
      RESULTS: New users of statins included 983 social assistance recipients who were
      observed for a total of 2,439,153 person-days. Median persistence on statin
      treatment was 173 (95% CI = 155, 204) days. Only 13% of patients persisted for 5
      years of treatment. A higher index of chronic morbidity, pre-existing
      cardiovascular disease, and previous use of nicotinic acid were predictive of
      longer persistence on statin medication. Those patients whose first statin
      dispensation was for lovastatin discontinued treatment earlier than those whose
      first dispensation was for pravastatin or simvastatin. CONCLUSIONS: New users
      showed low persistence on statins in a cohort of socially assisted persons aged
      45-64, in spite of the minimal financial cost of the drug for such beneficiaries
      of Quebec's provincial health plan.

PMID- 16464202
TI  - Early modelling for assessing health and economic outcomes of drug therapy.
AB  - Models for assessing health and economic outcomes of new drugs have an increasing
      role in the early phases of drug development. Their input into go/no go and
      priority setting decisions can reveal that further development of a drug is
      unattractive from an economic viewpoint, or that developing a certain indication
      is more attractive than another. They may also influence the later choice of
      indication, positioning, comparators, length of follow-up, and other elements in
      the further development of drugs. Their specific nature, characterized by limited
      budget, timelines and data availability should not necessarily lead to
      compromises in design and conduct. It is argued that high quality early models
      form the breeding ground for later solid evidence on value for money, and are
      consequently both worthwhile to the pharmaceutical industry and to health care
      decision-makers and payers.

PMID- 16464203
TI  - Introduction to diabetes special issue of value in health.

PMID- 16464204
TI  - Epidemiology and clinical presentation of type 2 diabetes.

PMID- 16464205
TI  - Economic evaluations relating to diabetes: a descriptive review and their
      compliance with guidance.
AB  - From a search of the Health Economics Evaluations Database (HEED), 301 studies
      relating to diabetes-related interventions were identified. Of these, 223 studies
      contained some original data, i.e., were applied studies. Over the 1990s, the
      number of studies undertaken in this area appears to be increasing year on year,
      and more of the studies are applicable to the USA than to all other countries
      combined. Most studies are peer reviewed, the main type of analysis is cost
      consequence, and the interventions most often assessed are pharmaceutical and
      care services. Both the public and the private sectors sponsor many of these
      studies. However, only a fraction of these studies appear to accord with guidance
      for good economic evaluation. For example, when the search criteria were
      tightened to capture only those studies that consider both outcomes and costs,
      173 studies were identified. Narrowing the search criteria to capture only those
      studies that were based on randomized controlled trial (RCT) or modeling data-the
      methods recommended by the US Panel and the National Institute of Clinical
      Excellence (NICE)-reduced the sample to 56 studies. With specific focus on those
      studies that evaluated pharmaceuticals, only the modeling approach appeared to
      show any compliance at all with another key recommendation of the existing
      guidance on methods; that of using outcome measures that are applicable to a long
      term time horizon. Though modeling does offer certain advantages over RCTs (for
      example, a larger range of comparators can be more readily incorporated, long
      term outcome measures can be more easily and inexpensively estimated), modeling
      results have less internal validity. Also, modeling in itself relies on good RCT
      data. Therefore, the results of economic evaluations should be interpreted with
      care, irrespective of whether they are principally based on RCT or model-based
      methods.

PMID- 16464206
TI  - Health-related quality of life measurement in type 2 diabetes.
AB  - Type 2 diabetes has significant adverse effects on health-related quality of life
      (HRQoL). A vast array of questionnaires has been used to measure HRQoL in
      diabetes patients, contributing to the difficulty of selecting instruments for
      future research. To systematically evaluate these measures, a literature search
      was undertaken to identify relevant publications. This paper summarizes the
      generic, diabetes-specific, and psychological measures utilized to evaluate
      persons with type 2 diabetes, and highlights related findings. Generic
      instruments demonstrate significant reductions in health status compared with
      other chronic disease populations and healthy controls. Multiple diabetes
      specific measures are available to assess domains affected by the disease,
      including symptoms, worries, self-care, locus of control, functional ability,
      social support, and sexual functioning. Psychological measures show that type 2
      diabetes is frequently associated with adverse psychological effects,
      particularly depression. Since much of this research has been cross-sectional in
      nature, little is known about responsiveness of many of the HRQoL measures to
      clinical change and treatment effects. It is clear that HRQoL results are
      influenced by multiple patient and disease factors, particularly age, gender, and
      the presence and severity of disease complications and comorbid conditions. These
      factors should be considered in the design and analysis of HRQoL evaluations in
      type 2 diabetes patients. Selection of instruments for future research will
      therefore require careful evaluation of study design and objectives, population
      characteristics, the presence of disease-related factors, and outcomes of
      interest.

PMID- 16464207
TI  - Short-run associations between medical care expenditures and adherence to
      clinical practice guideline-based measures for diabetes.
AB  - OBJECTIVES: To estimate relationships between medical care expenditures in 1996
      and adherence to seven guideline-based measures for diabetes. METHODS AND DATA:
      Nonlinear exponential regression analyses were used to estimate relationships
      between medical care expenditures in 1996 and adherence to guideline-based
      measures that year, adjusting for differences in patients' demographics,
      location, plan type, and severity of illness. Adherence to criteria regarding
      physician visits, eye exams, blood sugar tests, urinalysis, triglyceride tests,
      total cholesterol tests, and HDL cholesterol tests was studied for 18,403
      patients in 35 health plans. RESULTS: Average total medical expenditures would be
      $713 higher if all patients were treated according to the guideline-based
      measures in 1996, compared to what expenditures would be if no patients were
      treated that way. Average diabetes-related expenditures would be about $322
      higher. Two important exceptions to this pattern were for adherence to the
      suggested frequency of hemoglobin A1c blood sugar tests and ophthalmology visits
      for dilated eye exams. Having the recommended number of these tests was
      associated with significantly lower total expenditures. CONCLUSIONS: In general,
      adherence to clinical practice guideline-based measures was more costly than
      deviating from those criteria, in the short-run. Perhaps expenditures should be
      higher for many patients who are not treated according to guidelines. Randomized
      studies with more years of follow-up should be conducted to assess whether short
      term investments in guideline adherence pay off with lower medical expenditures
      and greater levels of health in the long term.

PMID- 16464208
TI  - The cost-effectiveness of treating diabetic lower extremity ulcers with
      becaplermin (Regranex): a core model with an application using Swedish cost data.
AB  - OBJECTIVES: The objective of this study was to develop a model capable of
      assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower
      extremity ulcers with becaplermin gel (Regranex) plus good wound care (GWC)
      relative to treating them with GWC alone. METHODS: A Markov simulation model was
      developed that includes six health states: Uninfected Ulcer, Infected Ulcer,
      Gangrene, Healed Ulcer, Healed Ulcer-History of Amputation, and Deceased. To
      predict clinical outcomes, information was taken from a specially designed
      prospective 9-month follow-up study of 183 neuropathic patients in the US treated
      with GWC. Cost of treatment data were taken primarily from a study of a cohort of
      314 patients in Sweden. The efficacy of becaplermin was assumed equal to that
      achieved in a pooled analysis of four randomized clinical trials. A model
      application provides expected clinical outcomes for a cohort of patients. Annual
      treatment costs per patient were estimated using treatment practice and unit
      prices from Sweden. RESULTS: Due to a higher rate of healing and a shorter
      average healing time, treatment with becaplermin gel was predicted to increase
      the average number of months spent in the healed state over the first year
      following development of an ulcer by 24% relative to GWC alone. In addition, the
      corresponding number of amputations was 9% lower for the becaplermin-treated
      cohort. The average expected cost of $12,078 US for an individual treated with
      GWC alone declines to $11,708 US for one treated with becaplermin, in spite of
      $1262 becaplermin costs. Expenses related to topical treatment and inpatient care
      account for 83% of the resources conserved. CONCLUSIONS: Our results suggest that
      in Sweden treatment with becaplermin in conjunction with GWC consumes fewer
      resources and generates better outcomes than treatment with GWC alone for
      diabetic neuropathic ulcers. In light of the high and increasing incidence of
      such ulcers, the potential savings in costs and suffering may be important.
      Results are difficult to extrapolate internationally because they are strongly
      related to country-specific treatment practices and price levels.

PMID- 16464209
TI  - Health-related quality of life in type 2 diabetes (TARDIS-2).
AB  - BACKGROUND: Type 2 diabetes is now recognized as a major public health concern
      but its burden on society is under-researched. METHODS: T(2)ARDIS was a postal
      survey of 1578 people with type 2 diabetes across four UK centres, incorporating
      measures of resource use, treatment satisfaction and health-related quality of
      life (HrQoL). The findings included data on the EQ-5D that enabled the HrQoL
      burden of the disease to be established by comparison with equivalent data for
      the general population and the diabetic population as a whole from the 1996
      Health Survey of England. RESULTS: The results indicate a significant deficit
      experienced by people with type 2 diabetes vs. their age group peers in the
      general population. The proportion of T(2)ARDIS respondents reporting problems
      increases in relation to the presence of complications, and microvascular
      complications appear to have more impact than macrovascular complications.
      CONCLUSIONS: This confirms the need for treatment policies to focus on reducing
      the risk of such complications and hence improve patients' HrQoL.

PMID- 16464210
TI  - The bond and burden of caring.

PMID- 16464211
TI  - Group psychotherapy with children on an inpatient unit: the MEGA group model.
AB  - TOPIC: Psychotherapy group intervention with children based on the use of
      community meeting. PURPOSE: To describe a model group intervention that is based
      on developmental level and applicable across a broad spectrum of behavioral and
      psychiatric disorders. The purpose of this paper is to discuss the development of
      this model on one inpatient unit, the benefits of the model and implication for
      future research, including a simple model of the stages of group development.
      SOURCES: A review of the literature and the author's experience in the
      development of a model group intervention. CONCLUSION: The model is a flexible
      and broadly applicable one, which may be utilized by a variety of staff,
      including relatively inexperienced line workers.

PMID- 16464212
TI  - A comparison of screening instruments for depression in postpartum adolescents.
AB  - TOPIC: It is important to screen postpartum adolescents for depression during
      routine healthcare visits so that depression can be identified and treated.
      PURPOSE: The purpose of the manuscript is to compare available depression
      screening instruments and to provide guidance to healthcare providers on choice
      of instrument. SOURCES USED: Published studies. CONCLUSIONS: In order to capture
      the common symptoms of adolescent and postpartum depression, a combination of
      screening instruments should be used.

PMID- 16464213
TI  - Effectiveness of continuing nursing education program in child psychiatry.
AB  - PROBLEM: Program evaluation of the effectiveness of two continuing nursing
      education programs (CNE) in child psychiatry in India. METHODS: Pre- and
      postevaluation of a total of 51 nurses attending a 10-day CNE program, using a 30
      item (six-domain) questionnaire according to CNE topics in child psychiatry.
      FINDINGS: The CNE program resulted in significant increase in the total scores as
      well as scores in several sub-domains in the field of child psychiatry.
      CONCLUSIONS: In a country that does not offer degree programs that integrate
      psychiatric nursing into the curriculum, CNE programs are an important
      educational option for nurses. The CNE program offered in this study, comprising
      lectures, discussion, interactive sessions, and case demonstrations totaling 60
      hr across 10 days, was effective in improving the level of knowledge of nurses.
      It was equally beneficial for senior as well as less experienced nurses.

PMID- 16464214
TI  - Paradigm shifts in inpatient psychiatric care of children: approaching child- and
      family-centered care.
AB  - TOPIC: This article describes the components of child- and family-centered care,
      including a review of the literature about the delivery of family-centered care
      and the barriers that often prevent the provision of such care. The article
      describes an inpatient child psychiatric unit that has implemented an approach to
      care that embraces these principles. The changes in structures and policies that
      the unit adopted are described, with specific examples cited as illustrations of
      the components of this care. PURPOSE: To describe the elements of child- and
      family-centered care and the ways in which this model of care may be implemented
      on inpatient child psychiatric units. SOURCES USED: Literature review including
      journal reports and articles and books. CONCLUSIONS: Preliminary outcomes are
      encouraging in the decrease in use of practices such as restraint and seclusion,
      and physical holds. Further research examining parents' satisfaction is warranted
      in determining the success of such endeavors.

PMID- 16464217
TI  - Nonstimulant medications for the treatment of ADHD.

PMID- 16464219
TI  - Symptoms, course, and complications of abdominal attacks in hereditary angioedema
      due to C1 inhibitor deficiency.
AB  - OBJECTIVES: Recurrent abdominal attacks belong to the cardinal and most
      distressing symptoms of hereditary angioedema (HAE) due to C1 inhibitor
      deficiency. They are characterized by crampy pain, but may include vomiting,
      diarrhea, and other features. Detailed clinical data about the symptoms and
      course of abdominal attacks have not been reported. METHODS: We retrospectively
      observed a total of 33,671 abdominal attacks in 153 patients with HAE including a
      prospectively examined subgroup of 23 patients. Symptoms, course, frequency of
      attacks, and complications were analyzed. RESULTS: The relation of mild,
      moderate, and severe attacks was 1:1.4:5.6 in the prospective part of the study.
      Extra-abdominal symptoms preceded the abdominal symptoms. The mean maximal pain
      score was 8.4 (range 1-10). Vomiting occurred in 73% (24,696) and diarrhea in 41%
      (13,682) of the attacks. Circulatory collapse accompanied 4.4% (1,468) of the
      attacks, with loss of consciousness (LOC) occurring in 2.2% (739). Nine patients
      could clearly distinguish two types of abdominal attacks: vomiting and diarrhea.
      Rare complications included tetany, hemorrhagic stools, and intussusception of
      the colon. In 28% (43) of the patients, recurrent abdominal attacks had started
      before the characteristic swelling of the skin had ever occurred. A model is
      proposed to classify the severity of the attacks and to describe the clinical
      course. CONCLUSIONS: Abdominal attacks in HAE constitute a more disabling and
      complex syndrome than previously assumed. Our results add to the understanding of
      symptoms and course of HAE and may aid in the early recognition of an impending
      attack and improve clinical management.

PMID- 16464221
TI  - Pregnancy in autoimmune hepatitis: outcome and risk factors.
AB  - OBJECTIVE: Autoimmune hepatitis (AIH) may influence pregnancy outcome and
      pregnancy may affect AIH. We aimed at analyzing the disease course in pregnant
      AIH patients and at identifying disease-related risk factors for adverse
      pregnancy outcome. PATIENTS AND METHODS: AIH patients with at least one pregnancy
      were identified at four liver units. The patients' records and the data obtained
      by detailed questionnaires were analyzed retrospectively. Forty-two pregnancies
      of 22 AIH patients were included. RESULTS: The rate of adverse pregnancy outcome
      was 26%; a medical explanation could be elucidated in only 4 of 11 pregnancies
      with adverse outcome. Of note, the 7 unexplained adverse pregnancy outcomes were
      highly associated with the presence of antibodies to SLA/LP (odds ratio 51; p <
      0.003) and Ro/SSA (odds ratio 27; p < 0.02). Of 35 live births, 30 children
      developed normally over a mean observation period of nearly 5 yr. Eleven of these
      had been exposed to azathioprine in utero. The rate of serious maternal
      complications was 9% and a high rate (52%) of postpartum flares was noted.
      CONCLUSIONS: The presence of autoantibodies may be a risk factor for adverse
      pregnancy outcome in AIH patients. Close monitoring of both mother and fetus
      seems advisable due to a significant rate of maternal and fetal complications.

PMID- 16464220
TI  - A study of candidate genotypes associated with dyspepsia in a U.S. community.
AB  - BACKGROUND: The role of genetic predisposition to the development of dyspepsia is
      unclear. Recently, a significant association was reported with CC genotype of
      GNbeta3. AIM: To explore the association of candidate genotypes altering
      adrenergic, serotonergic, CCKergic, and G protein functions, and dyspepsia in a
      sample from a U.S. community. METHODS: Dyspeptics and healthy controls were
      identified among community respondents who had been randomly selected to complete
      validated questionnaires. Other diseases were excluded by face-to-face history
      and physical examination. Polymorphisms of candidate genes for alpha(2A),
      alpha(2C), 5-HT(1A), 5-HT(2A), 5-HT(2C), CCK-1 receptors and CCK promoter,
      GNbeta3 protein, and SERT-promoter (SERT-P) were studied. The association between
      polymorphisms and meal-related or meal-unrelated dyspepsia, high somatic symptom
      scores, and somatization were evaluated using Fisher's exact test. RESULTS: DNA
      was available from 41 dyspeptics and 47 healthy controls from Olmsted County.
      Community dyspepsia unrelated to meals was associated with both homozygous
      GNbeta3 protein 825T and C alleles. There were no significant associations with
      meal-related dyspepsia. Using Rome II subgroups, the same genotype was associated
      with dysmotility-like and other dyspepsia. Higher somatization scores were not
      significantly associated with any of the candidate genes when considered as
      single factors. CONCLUSION: Meal-unrelated dyspepsia in a U.S. community study is
      associated with the homozygous 825T or C alleles of GNbeta3 protein. Candidate
      genes controlling adrenergic, serotonergic, and CCKergic functions do not appear
      to be associated with dyspepsia.

PMID- 16464222
TI  - Cryptogenic cirrhosis and NAFLD: are they related?
AB  - Cryptogenic cirrhosis (CC), literally meaning cirrhosis of obscure or unknown
      origin, is a diagnosis of exclusion. The circumstantial evidence indicates that
      nonalcoholic fatty liver disease (NAFLD) is perhaps one of the important causes
      of CC. There is also evidence, especially from the European literature, that some
      patients with CC may have undiagnosed or burnt-out autoimmune hepatitis (AIH).
      Other rare causes may include "unknown" viral (non-A, non-B, non-C) hepatitis,
      and occult alcoholism. In this review, we examine the role of NAFLD and other
      causes in the pathogenesis of CC, and the impact of obesity on patients with
      chronic liver disease.

PMID- 16464223
TI  - Utility of serological markers in predicting the early occurrence of
      complications and surgery in pediatric Crohn's disease patients.
AB  - BACKGROUND AND OBJECTIVES: Many Crohn's disease (CD) patients develop
      complications (fistulae and abscesses), and require surgery, often repeatedly and
      at variable instances. Identifying serological markers that determine their early
      or repeated manifestation can enable implementing more aggressive preventive
      strategies. Our objective was to study the ability of serological markers for
      predicting development of early (first) and recurrent complications or
      requirement for surgery. METHODS: Serum anti-Saccharomyces cervisiae (ASCA) (IgA
      & IgG) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) were assayed
      close to diagnosis in a pediatric cohort of CD patients identified between 1996
      and 1998. At diagnosis and follow-up, information was acquired on demographic and
      clinical features of disease. Relation between ASCA and clinical events was
      studied using adjusted Cox-proportional hazards modeling. The relative rates of
      recurrent clinical events according to the marker measures were compared.
      RESULTS: The mean age (SD) at diagnosis was 11.2 (3.4) yr. Among 139 patients, 35
      (25.9%) and 31 (22.3%) acquired one or more CD related surgery or complication,
      respectively. Time to occurrence of the first complication was lower among
      patients ASCA+ (IgA or IgG) (hazards ratio (HR) = 2.33; 95% confidence interval
      (CI) = 0.99-5.50) and among those with higher ASCA-IgA titers (HR = 1.20; 95% CI
      = 1.08-1.34). The rates of recurrent complications were higher among those
      positive or with higher ASCA titers. ASCA did not predict time to undergoing
      surgery independent of complications, and was unrelated to the occurrence of
      recurrent surgeries. CONCLUSIONS: Our study shows that serum ASCA measured close
      to diagnosis can determine the occurrence of early complications in pediatric CD.
      Preventive treatment targeted toward these susceptible patients could potentially
      modify the disease course.

PMID- 16464224
TI  - Pathophysiology and role of biofeedback therapy in solitary rectal ulcer
      syndrome.
AB  - BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a behavioral disorder whose
      pathophysiology is incompletely understood. Likewise, its treatment, particularly
      the role of biofeedback therapy (BT) is unclear. AIM: To evaluate anorectal
      function and morphology and to assess efficacy of BT. METHODS: Eleven patients
      (8f) with refractory SRUS underwent symptom assessments, anorectal manometry,
      defecography, balloon expulsion test, and sigmoidoscopy. Physiological tests were
      also performed in 15 (11f) healthy controls. Subsequently, SRUS patients
      underwent biofeedback treatment. Symptoms and manometry were reassessed. RESULTS:
      Nine (82%) patients exhibited dyssynergia ( p < 0.001). Rectal sensory thresholds
      were decreased (p < 0.04). After biofeedback, straining effort and stool
      frequency decreased ( p < 0.05), and bowel satisfaction score (VAS) improved ( p
      < 0.001). Digital maneuvers were discontinued by all five patients and bleeding
      stopped in 56%. The defecation index increased ( p < 0.05), dyssynergia
      normalized, and balloon expulsion time decreased ( p < 0.05). There was complete
      healing in 4 (36%), > or =50% healing in 2 (18%), and <50% healing in 4 (36%)
      patients. CONCLUSIONS: SRUS associated with excessive straining, digital
      disimpaction, rectal hypersensitivity, dyssynergic defecation, and prolonged
      evacuation. BT may improve symptoms and anorectal function and facilitate
      healing.

PMID- 16464225
TI  - Differences between painless and painful constipation among community women.
AB  - BACKGROUND: In the Rome II criteria, patients with both constipation and
      abdominal pain (AP) (i.e., "painful constipation" (PC)), who do not satisfy
      criteria for irritable bowel syndrome (IBS) are included in the same functional
      constipation (FC) category as patients with constipation without AP (i.e.,
      "painless constipation" (PLC)). What differences, if any, exist between FC
      without (i.e., PLC) and with AP (i.e., PC) are unclear. METHODS: To compare
      clinical features among PLC, PC, constipation-predominant IBS (C-IBS), and non-C
      IBS, a validated questionnaire was mailed (with telephone follow-up of
      nonresponders) to an age-stratified random sample of 5,200 adult women in Olmsted
      County, Minnesota. RESULTS: Altogether, 2,800 women (53%) responded. The age
      adjusted prevalence of PLC (7.1 per 100; 95% confidence interval (95% CI), 6.2
      8.0) was higher compared to PC (0.9 per 100; 95% CI, 0.6-1.2). Compared to PLC,
      patients with PC reported worse general health (i.e., excellent or very good =
      37.5% vs 51.2%), more somatic symptoms (mean score = 1.3 vs 0.9), and urinary
      urgency (% often = 58% vs 32%), and had a higher prevalence of hysterectomy.
      Bowel symptoms significantly impacted > or =1 domain of quality of life (QOL) in
      18% of PC versus 9% of PLC. In a logistic discriminant model, age, general
      health, impact of bowel symptoms on QOL, somatic symptoms, and urinary urgency
      independently discriminated between bowel subtypes. CONCLUSIONS: Patients with PC
      more closely resemble those with C-IBS than PLC. Consideration should be given to
      separating PC from PLC in the Rome criteria and in therapeutic trials.

PMID- 16464226
TI  - Addition of esophageal impedance monitoring to pH monitoring increases the yield
      of symptom association analysis in patients off PPI therapy.
AB  - BACKGROUND: The additional yield of esophageal impedance monitoring in
      identification of reflux as the cause of reflux symptoms is unknown. OBJECTIVES:
      To compare the yield of symptom-reflux association analysis of combined
      esophageal pH-impedance data with the yield of analysis of pH data alone.
      METHODS: In 60 patients with symptoms of heartburn and regurgitation combined, 24
      h pH-impedance monitoring was performed. Acid-suppressive medication was stopped
      1 wk in advance. Patients (48) with at least one symptom during the measurement
      period were selected for further analysis. Patients were instructed to note the
      time and nature of their symptoms. Eleven types of reflux episodes were defined,
      based on combinations of magnitude of the pH drop, nadir pH, and nature of the
      refluxate (gas and liquid) on impedance tracings. Symptom association analysis
      symptom index, the symptom sensitivity index, and the symptom association
      probability (SAP)-was performed for each definition of reflux. RESULTS: The
      proportion of patients with a positive SAP (> or =95.0%) varied between 62.5% and
      77.1%, depending on the definition of reflux episodes. When both pH and impedance
      parameters were used to identify reflux, a higher proportion of patients had a
      positive SAP than with pH alone (77.1%vs 66.7%, p < 0.05). Symptom association
      analysis for acidic and weakly acidic reflux separately did not result in a
      higher yield than analysis with all reflux episodes pooled, regardless of pH.
      CONCLUSION: In patients off proton pump inhibitor, the addition of impedance
      monitoring to esophageal pH monitoring leads to an increase in the proportion of
      patients in whom an association between reflux episodes and symptoms can be
      identified.

PMID- 16464227
TI  - Endoscopic mucosal resection.
AB  - Endoscopic mucosal resection (EMR) is a promising therapeutic option for removal
      of superficial carcinomas or premalignant lesions throughout the gastrointestinal
      tract. This review discusses indications and the several techniques of EMR in
      early tumors of esophagus, stomach, duodenum, and colon. EMR is not yet widely
      utilized in the West. However, great benefits may be obtained from this non
      invasive technique after an accurate evaluation of patients and a careful staging
      of lesions that may assess the depth of infiltration and exclude the presence of
      lymph node metastases. EMR permits a complete removal of the lesion with
      histologic assessment of the entire specimen and the change in the pathologic
      stage in a significant number of patients. To minimize the risk of serious
      complications (mostly bleeding and perforation), only experienced endoscopists
      should undertake EMR in an appropriate environment. Data from literature are
      encouraging on the use of EMR, but a long-term follow-up of a large number of
      patients is necessary to confirm the effectiveness of this therapy.

PMID- 16464228
TI  - Dermatological manifestations in primary biliary cirrhosis patients: a case
      control study.
AB  - OBJECTIVES: Primary biliary cirrhosis (PBC), a disease of probable autoimmune
      etiology that affects the small intrahepatic bile ducts of mainly middle-aged
      women is commonly associated with pruritus, xanthomatous lesions, and melanosis.
      We conducted a prospective study to systematically describe the skin disorders of
      a group of PBC patients. METHODS: A prospective evaluation and analysis of
      dermatological manifestations including oral and genital lesions was carried out,
      in 49 PBC patients (45 females and 4 males). Median age 63 yr (range 35-87 yr).
      They were compared with 45 age and sex matched controls, selected among persons
      attending the dermatologic outpatient clinic. RESULTS: A total of 330 skin
      disorders were found in the 49 PBC patients versus 76 in the 45 controls; 31.5%
      of all lesions were skin fungal infections. Of all lesions analyzed with the
      Bonferroni rule of multiple comparisons significantly more common in PBC patients
      were plantar mycoses, onychomycoses, and interdigital mycoses. Pruritus was found
      in 69.3% of patients versus 22.2% of controls, xerosis in 69.3%versus 2.2%,
      dermographism in 57.1%versus 4.4%, and melanosis in 46.9%versus 0%. In 38.7% of
      the PBC patients the dermatologic lesion was the presenting symptom. CONCLUSIONS:
      PBC patients present with a wide variety of cutaneous manifestations varying in
      severity. Multiple skin fungal infections have been found even in the early
      stages. Since in more than one third of our PBC patients the dermatologic lesion
      was the presenting sign or symptom leading to diagnosis we believe that
      physicians should be aware so that a prompt and early diagnosis may be achieved.

PMID- 16464229
TI  - Perception of electrocutaneous stimuli in irritable bowel syndrome.
AB  - BACKGROUND AND AIM: Irritable bowel syndrome (IBS) and fibromyalgia syndrome
      (FMS) are common conditions with some similarities, but different perceptual
      responses to somatic and visceral stimuli. The purpose of this study was to
      assess in a large group of IBS patients the somatic perception by transcutaneous
      electrical nerve stimulation (TENS) and its relation to the level of severity and
      presence of FMS. METHODS: In 99 patients grouped by the validated functional
      bowel disorder severity index (FBDSI) in mild, moderate, and severe IBS and in 33
      healthy controls (HC), we studied discomfort thresholds and perception of somatic
      stimuli at control (hands and elbows) and active (trapezius) sites by TENS and by
      using a specific questionnaire. RESULTS: The use of TENS showed that IBS showed
      significant higher thresholds and lower perception cumulative score compared to
      HC. The severity of IBS is significantly associated with age and mean control
      site values for discomfort and borderline associated with gender in the ordinal
      model constructed for the ascending series protocol. The severity of IBS is also
      significantly associated with the active cumulative perception score in the long
      stimulus protocol. Due to limited sample size of IBS men with FMS, analyses of
      discomfort thresholds and cumulative perception score by FMS were done only for
      women. IBS women without FMS had significantly higher mean control site values
      for discomfort and significantly lower active cumulative perception score than
      HC. IBS women with FMS had significantly lower mean active site values for
      discomfort thresholds than IBS women without FMS (Dunn's test p < 0.05).
      CONCLUSIONS: IBS patients showed somatic hypoalgesia to electrical stimuli. The
      severity of IBS and the presence of FMS influence the perception of somatic
      stimuli induced by TENS.

PMID- 16464230
TI  - Hypokalemic rhabdomyolysis without watery diarrhea: an unexpected presentation of
      a pancreatic neuro-endocrine tumor.
AB  - Pancreatic polypeptide (PP) islet cell tumors are usually not associated with a
      distinct clinical syndrome, although some reports suggest that they can cause a
      watery diarrhea syndrome similar to vasoactive intestinal polypeptide (VIP) cell
      tumors. We report the case of a young woman with an unusual presentation of a
      pancreatic neuroendocrine tumor mainly secreting PP. The patient developed a
      reversible hypokalemic rhabdomyolysis very likely secondary to the presence of
      the tumor. The myopathy resolved following the restoration of normokaliemia using
      potassium supplementation and a partial laparoscopic pancreasectomy. Isolated
      cases of hypokalemic rhabdomyolysis induced by intestinal diseases have been
      described in literature but these did not include gastroenteropancreatic
      neoplasms. We suggest that pancreatic neuroendocrine tumors should be added to
      the list of intestinal diseases capable of producing hypokalemic myopathy.

PMID- 16464232
TI  - Postsynaptic recruitment of Dendrin depends on both dendritic mRNA transport and
      synaptic anchoring.
AB  - Synaptic plasticity and memory formation involve remodeling of the postsynaptic
      cytoskeleton, a process that is in part based on both local translation of
      dendritic mRNAs and synaptic recruitment of newly synthesized proteins. The
      postsynaptic component Dendrin that is encoded by a dendritically localized mRNA
      is thought to modulate the structure of the synaptic cytoskeleton. However,
      molecular mechanisms that control extrasomatic Dendrin mRNA transport and
      postsynaptic protein recruitment are unknown. The data presented here reveal that
      Dendrin interacts with the cytoskeletal components alpha-actinin and Maguk with
      inverted orientation (MAGI) or synaptic scaffolding molecule (S-SCAM). The latter
      retains Dendrin in the cytoplasm of mammalian cells and prevents its nuclear
      import. Furthermore in neurons, postsynaptic clustering of Dendrin requires
      dendritic targeting of its messenger RNA (mRNA), a process that is mediated by a
      sequence motif within the 3' untranslated region. In summary our finding suggest
      that postsynaptic recruitment of Dendrin appears to critically depend on both
      local protein synthesis and association with the synaptic scaffolding protein
      MAGI/S-SCAM. Its nuclear localization capacity further points to a function in
      retrograde signaling from the synapse to the nucleus.

PMID- 16464233
TI  - Astrocyte control of fetal cortical neuron glutathione homeostasis: up-regulation
      by ethanol.
AB  - Ethanol increases apoptotic neuron death in the developing brain and at least
      part of this may be mediated by oxidative stress. In cultured fetal rat cortical
      neurons, Ethanol increases levels of reactive oxygen species (ROS) within minutes
      of exposure and reduces total cellular glutathione (GSH) shortly thereafter. This
      is followed by onset of apoptotic cell death. These responses to Ethanol can be
      blocked by elevating neuron GSH with N-acetylcysteine or by co-culturing neurons
      with neonatal cortical astrocytes. We describe here mechanisms by which the
      astrocyte-neuron gamma-glutamyl cycle is up-regulated by Ethanol, enhancing
      control of neuron GSH in response to the pro-oxidant, Ethanol. Up to 6 days of
      Ethanol exposure had no consistent effects on activities of gamma-glutamyl
      cysteine ligase or glutathione synthetase, and GSH content remained unchanged (p
      < 0.05). However, glutathione reductase was increased with 1 and 2 day Ethanol
      exposures, 25% and 39% for 2.5 and 4.0 mg/mL Ethanol by 1 day, and 11% and 16%
      for 2.5 and 4.0 mg/mL at 2 days, respectively (p < 0.05). A 24 h exposure to 4.0
      mg/mL Ethanol increased GSH efflux from astrocyte up to 517% (p < 0.05). Ethanol
      increased both gamma-glutamyl transpeptidase expression and activity on astrocyte
      within 24 h of exposure (40%, p = 0.05 with 4.0 mg/mL) and this continued for at
      least 4 days of Ethanol treatment. Aminopeptidase N activity on neurons increased
      by 62% and 55% within 1 h of Ethanol for 2.5 and 4.0 mg/mL concentration,
      respectively (p < 0.05), remaining elevated for 24 h of treatment. Thus, there
      are at least three key points of the gamma-glutamyl cycle that are up-regulated
      by Ethanol, the net effect being to enhance neuron GSH homeostasis, thereby
      protecting neurons from Ethanol-mediated oxidative stress and apoptotic death.

PMID- 16464234
TI  - Aminoguanidine inhibits caspase-3 and calpain activation without affecting
      microglial activation following neonatal transient cerebral ischemia.
AB  - Microglial cells, the resident macrophages of the CNS, can be both beneficial and
      detrimental to the brain. These cells play a central role as mediators of
      neuroinflammation associated with many neurodegenerative states, including
      cerebral ischemia. Because microglial cells are both a major source of inducible
      nitric oxide synthase (iNOS)/nitric oxide (NO) production locally in the injured
      brain and are activated by NO-mediated injury, we tested whether iNOS inhibition
      reduces microglial activation and ischemic injury in a neonatal focal ischemia
      reperfusion model. Post-natal day 7 rats were subjected to a 2 h transient middle
      cerebral artery (MCA) occlusion. Pups with confirmed injury on diffusion-weighted
      magnetic resonance imaging (MRI) during occlusion were administered 300
      mg/kg/dose aminoguanidine (AG) or vehicle at 0, 4 and 18 h after reperfusion, and
      animals were killed at 24 or 72 h post-reperfusion. The effect of AG on
      microglial activation as judged by the acquisition of ED1 immunoreactivity and
      proliferation of ED1-positive cells, on activation of cell death pathways and on
      injury volume, was determined. The study shows that while AG attenuates caspase 3
      and calpain activation in the injured tissue, treatment does not affect the
      rapidly occurring activation and proliferation of microglia following transient
      MCA occlusion in the immature rat, or reduce injury size.

PMID- 16464235
TI  - Molecular identification and functional characterization of an adenylyl cyclase
      from the honeybee.
AB  - Cyclic AMP (cAMP) serves as an important messenger in virtually all organisms. In
      the honeybee (Apis mellifera), cAMP-dependent signal transduction has been
      implicated in behavioural processes as well as in learning and memory. Key
      components of cAMP-signalling cascades are adenylyl cyclases. However, the
      molecular identities and biochemical properties of adenylyl cyclases are
      completely unknown in the honeybee. We have cloned a cDNA (Amac3) from honeybee
      brain that encodes a membrane-bound adenylyl cyclase. The Amac3 gene is an
      orthologue of the Drosophila ac39E gene. The corresponding proteins share an
      overall amino acid similarity of approximately 62%. Phylogenetically, AmAC3
      belongs to group 1 adenylyl cyclases. Heterologously expressed AmAC3 displays
      basal enzymatic activity and efficient coupling to endogenous G protein
      signalling pathways. Stimulation of beta-adrenergic receptors induces AmAC3
      activity with an EC(50) of about 3.1 microm. Enzymatic activity is also increased
      by forskolin (EC(50) approximately 15 microm), a specific agonist of membrane
      bound adenylyl cyclases. Similar to certain biogenic amine receptor genes of the
      honeybee, Amac3 transcripts are expressed in many somata of the brain, especially
      in mushroom body neurones. These results suggest that the enzyme serves in
      biogenic amine signal transduction cascades and in higher brain functions that
      contribute to learning and memory of the bee.

PMID- 16464236
TI  - Interaction between interferon gamma and insulin-like growth factor-1 in
      hippocampus impacts on the ability of rats to sustain long-term potentiation.
AB  - There is compelling evidence to suggest that inflammation significantly
      contributes to neurodegenerative changes. Consistent with this is the observation
      that several neurodegenerative disorders are accompanied by an increase in the
      concentration of interleukin (IL)-1beta. IL-1beta has a negative impact on
      synaptic plasticity and therefore an increased concentration of IL-1beta, such as
      that in the hippocampus of the aged rat, is associated with a deficit in long
      term potentiation (LTP). IL-1beta is derived mainly from activated microglia but
      the trigger leading to this activation, specifically in the aged brain, remains
      to be identified. Here we examined the possibility that interferon (IFN)gamma may
      stimulate microglial activation and increase IL-1beta concentration, thereby
      inhibiting LTP. The IFNgamma concentration was increased in hippocampus prepared
      from aged, compared with young, rats and inversely correlated with the ability of
      rats to sustain LTP. Intracerebroventricular injection of IFNgamma inhibited LTP,
      and increased microglial activation was observed in both IFNgamma-injected and
      aged rats. The age-related increase in IFNgamma was accompanied by a decrease in
      the hippocampal concentration of insulin-like growth factor (IGF)-1. The evidence
      presented suggests that IGF-1 acts to antagonize the IFNgamma-induced microglial
      activation, the accompanying increase in IL-1beta concentration and the
      consequent deficit in LTP.

PMID- 16464237
TI  - Enhancement of nitric oxide production by association of nitric oxide synthase
      with N-methyl-D-aspartate receptors via postsynaptic density 95 in genetically
      engineered Chinese hamster ovary cells: real-time fluorescence imaging using
      nitric oxide sensitive dye.
AB  - The current quantitative study demonstrates that the recruitment of neuronal
      nitric oxide synthase (nNOS) beneath N-methyl-D-aspartate (NMDA) receptors, via
      postsynaptic density 95 (PSD-95) proteins significantly enhances nitric oxide
      (NO) production. Real-time single-cell fluorescence imaging was applied to
      measure both NO production and Ca(2+) influx in Chinese hamster ovary (CHO) cells
      expressing recombinant NMDA receptors (NMDA-R), nNOS, and PSD-95. We examined the
      relationship between the rate of NO production and Ca(2+) influx via NMDA
      receptors using the NO-reactive fluorescent dye, diaminofluorescein-FM (DAF-FM)
      and the Ca(2+)-sensitive yellow cameleon 3.1 (YC3.1), conjugated with PSD-95 (PSD
      95-YC3.1). The presence of PSD-95 enhanced the rate of NO production by 2.3-fold
      upon stimulation with 100 microm NMDA in CHO1(+) cells (expressing NMDA-R, nNOS
      and PSD-95) when compared with CHO1(-) cells (expressing NMDA-R and nNOS lacking
      PSD-95). The presence of nNOS inhibitor or NMDA-R blocker almost completely
      suppressed this NMDA-stimulated NO production. The Ca(2+) concentration beneath
      the NMDA-R, [Ca(2+)](NR), was determined to be 5.4 microm by stimulating CHO2
      cells (expressing NMDA-R and PSD-95-YC3.1) with 100 microm NMDA. By completely
      permealizing CHO1 cells with ionomycin, a general relationship curve of the rate
      of NO production versus the Ca(2+) concentration around nNOS, [Ca(2+)](NOS), was
      obtained over the wide range of [Ca(2+)](NOS). This sigmoidal curve had an EC(50)
      of approximately 1.2 microm of [Ca(2+)](NOS), implying that [Ca(2+)](NR) = 5.4
      microm can activate nNOS effectively.

PMID- 16464238
TI  - Zebrafish lacking Alzheimer presenilin enhancer 2 (Pen-2) demonstrate excessive
      p53-dependent apoptosis and neuronal loss.
AB  - Gamma-secretase cleavage, mediated by a complex of presenilin, presenilin
      enhancer (Pen-2), nicastrin, and Aph-1, is the final proteolytic step in
      generating amyloid beta protein found in brains of Alzheimer's disease patients
      and Notch intracellular domain critical for proper neuronal development. Here, we
      employ the zebrafish model to study the role of Pen-2 in neuronal survival. We
      found that (i) knockdown of Pen-2 using antisense morpholino led to a reduction
      of islet-1 positive neurons, (ii) Notch signaling was reduced in embryos lacking
      Pen-2 or other gamma-secretase components, (iii) neuronal loss in Pen-2 knockdown
      embryos is not as a result of a lack of neuronal precursor cells or cell
      proliferation, (iv) absence of Pen-2 caused massive apoptosis in the whole
      animal, which could be suppressed by simultaneous knockdown of the tumor
      suppressor p53, (v) loss of islet-1 or acetylated tubulin positive neurons in Pen
      2 knockdown embryos could be partially rescued by knockdown of p53. Our results
      demonstrate that knockdown of Pen-2 directly induces a p53-dependent apoptotic
      pathway that contributes to neuronal loss and suggest that Pen-2 plays an
      important role in promoting neuronal cell survival and protecting from apoptosis
      in vivo.

PMID- 16464239
TI  - Pramipexole protects against MPTP toxicity in non-human primates.
AB  - The neurotoxin MPTP induces nigral dopaminergic cell death in primates and
      produces a partial model of Parkinson's disease (PD). Pramipexole is a D2/D3
      dopamine receptor agonist used in the symptomatic treatment of PD, and which also
      protects neuronal cells against dopaminergic toxins in vitro. We now demonstrate
      that pramipexole partially prevents MPTP toxicity in vivo in a primate species.
      Common marmosets were repeatedly treated with pramipexole either before,
      coincidentally with, or after low-dose MPTP treatment designed to induce a
      partial lesion of the substantia nigra. Animals pretreated with pramipexole had a
      significantly greater number of surviving tyrosine hydroxylase (TH) positive
      neurones in the pars compacta of the substantia nigra. Pramipexole pretreatment
      also prevented degeneration of striatal dopamine terminals. Treatment with
      pramipexole concurrently with MPTP or following MPTP did not prevent TH-positive
      cell loss. Pramipexole pretreatment appears to induce adaptive changes that
      protect against dopaminergic cell loss in primates.

PMID- 16464240
TI  - Effects of extracellular matrix-degrading proteases matrix metalloproteinases 3
      and 9 on spatial learning and synaptic plasticity.
AB  - Rats learning the Morris water maze exhibit hippocampal changes in synaptic
      morphology and physiology that manifest as altered synaptic efficacy. Learning
      requires structural changes in the synapse, and multiple cell adhesion molecules
      appear to participate. The activity of these cell adhesion molecules is, in large
      part, dependent on their interaction with the extracellular matrix (ECM). Given
      that matrix metalloproteinases (MMPs) are responsible for transient alterations
      in the ECM, we predicted that MMP function is critical for hippocampal-dependent
      learning. In support of this, it was observed that hippocampal MMP-3 and -9
      increased transiently during water maze acquisition as assessed by western
      blotting and mRNA analysis. The ability of the NMDA receptor channel blocker
      MK801 to attenuate these changes indicated that the transient MMP changes were in
      large part dependent upon NMDA receptor activation. Furthermore, inhibition of
      MMP activity with MMP-3 and -9 antisense oligonucleotides and/or MMP inhibitor FN
      439 altered long-term potentiation and prevented acquisition in the Morris water
      maze. The learning-dependent MMP alterations were shown to modify the stability
      of the actin-binding protein cortactin, which plays an essential role in
      regulating the dendritic cytoskeleton and synaptic efficiency. Together these
      results indicate that changes in MMP function are critical to synaptic plasticity
      and hippocampal-dependent learning.

PMID- 16464241
TI  - The use of microarray technologies in clinical oncology.

PMID- 16464243
TI  - Routine management of locally advanced cervical cancer with concurrent radiation
      and cisplatin. Five-year results.
AB  - BACKGROUND: Globally, cervical cancer primarily affects socially disadvantaged
      women. Five randomized trials were the foundation for adopting cisplatin-based
      chemotherapy during radiation as the standard of care for high-risk patients
      after primary radical hysterectomy who require adjuvant radiation and for locally
      advanced patients treated with definitive radiation. These results were obtained
      in clinical trials performed in carefully prepared academic centers; hence, we
      sought to determine whether these results could be reproduced when patients were
      treated on an out-of-protocol basis. METHODS: We reviewed the files of 294
      patients with locally advanced cervical cancer who received radiation plus weekly
      cisplatin as routine management between 1999 to 2003, and analyzed treatment
      compliance, response rate, toxicity, and survival. RESULTS: A total of 294
      patients who received radiation and cisplatin were analyzed. Mean age was 43.8
      years (range, 26-68 years). The majority of cases were squamous cell carcinoma
      (87.8%), and distribution according to International Federation of Gynecology and
      Obstetrics (FIGO) stage was as follows: IB2-IIA, 23%; IIB, 53.3%, and IIIB, 23%;
      there were only two IVA cases. Overall, 96% of patients completed external beam,
      and intracavitary therapy. The majority of patients (67%) received the planned
      six courses of weekly cisplatin. Complete responses were achieved in 243 (83%)
      patients, whereas 51 (17%) had either persistent (32 patients, 10.8%) or
      progressive (19 patients, 6.4%) disease. At median follow-up (28 months; range, 2
      68 months), 36 patients (12.2%) have relapsed (locally 30.5, and systemically,
      69.5%). The most common toxicities were hematologic and gastrointestinal, in the
      majority of cases considered mild-moderate. At median follow-up (28 months;
      range, 2-68 months), overall and progression-free survival are 76.5 and 67%,
      respectively. CONCLUSION: Our results support use of chemoradiation with six
      weekly applications of cisplatin at 40 mg/m2 during external radiation for
      routine management of locally advanced cervical cancer.

PMID- 16464244
TI  - Regulation of the human LAT gene by the Elf-1 transcription factor.
AB  - BACKGROUND: The LAT gene encodes an intracellular adaptor protein that links cell
      surface receptor engagement to numerous downstream signalling events, and thereby
      plays an integral role in the function of cell types that express the gene,
      including T cells, mast cells, natural killer cells, and platelets. To date, the
      mechanisms responsible for the transcriptional regulation of this gene have not
      been investigated. RESULTS: In this study we have mapped the transcriptional
      start sites for the human LAT gene and localized the 5' and 3' boundaries of the
      proximal promoter. We find that the promoter contains both positive and negative
      regulatory regions, and that two binding sites for the Ets family of
      transcription factors have a strong, positive effect on gene expression. Each
      site binds the Ets family member Elf-1, and overexpression of Elf-1 augments LAT
      promoter activity. The promoter also contains a Runx binding site adjacent to one
      of the Ets sites. This site, which is shown to bind Runx-1, has an inhibitory
      effect on gene expression. Finally, data is also presented indicating that the
      identified promoter may regulate cell-type specific expression. CONCLUSION:
      Collectively, these results provide the first insights into the transcriptional
      regulation of the LAT gene, including the discovery that the Ets transcription
      factor Elf-1 may play a central role in its expression.

PMID- 16464246
TI  - The initial Mayo Clinic experience using high-frequency oscillatory ventilation
      for adult patients: a retrospective study.
AB  - BACKGROUND: High-frequency oscillatory ventilation (HFOV) was introduced in our
      institution in June 2003. Since then, there has been no protocol to guide the use
      of HFOV, and all decisions regarding ventilation strategies and settings of HFOV
      were made by the treating intensivist. The aim of this study is to report our
      first year of experience using HFOV. METHODS: In this retrospective study, we
      reviewed all 14 adult patients, who were consecutively ventilated with HFOV in
      the intensive care units of a tertiary medical center, from June 2003 to July
      2004. RESULTS: The mean age of the patients was 56 years, 10 were males, and all
      were whites. The first day median APACHE II score and its predicted hospital
      mortality were 35 and 83%, respectively, and the median SOFA score was 11.5.
      Eleven patients had ARDS, two unilateral pneumonia with septic shock, and one
      pulmonary edema. Patients received conventional ventilation for a median of 1.8
      days before HFOV. HFOV was used 16 times for a median of 3.2 days. Improvements
      in oxygenation parameters were observed after 24 hours of HFOV (mean PaO2/FIO2
      increased from 82 to 107, P < 0.05; and the mean oxygenation index decreased from
      42 to 29; P < 0.05). In two patients HFOV was discontinued, in one because of
      equipment failure and in another because of severe hypotension that was
      unresponsive to fluids. No change in mean arterial pressure, or vasopressor
      requirements was noted after the initiation of HFOV. Eight patients died (57 %,
      95% CI: 33-79); life support was withdrawn in six and two suffered cardiac
      arrest. CONCLUSION: During our first year of experience, HFOV was used as a
      rescue therapy in very sick patients with refractory hypoxemia, and improvement
      in oxygenation was observed after 24 hours of this technique. HFOV is a
      reasonable alternative when a protective lung strategy could not be achieved on
      conventional ventilation.

PMID- 16464245
TI  - Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme
      specific conditional mutant mice.
AB  - BACKGROUND: Lim1 is a homeobox gene that is essential for nephrogenesis. During
      metanephric kidney development, Lim1 is expressed in the nephric duct, ureteric
      buds, and the induced metanephric mesenchyme. Conditional ablation of Lim1 in the
      metanephric mesenchyme blocks the formation of nephrons at the nephric vesicle
      stage, leading to the production of small, non-functional kidneys that lack
      nephrons. METHODS: In the present study, we used Affymetrix probe arrays to
      screen for nephron-specific genes by comparing the expression profiles of control
      and Lim1 conditional mutant kidneys. Kidneys from two developmental stages,
      embryonic day 14.5 (E14.5) and 18.5 (E18.5), were examined. RESULTS: Comparison
      of E18.5 kidney expression profiles generated a list of 465 nephron-specific gene
      candidates that showed a more than 2-fold increase in their expression level in
      control kidney versus the Lim1 conditional mutant kidney. Computational analysis
      confirmed that this screen enriched for kidney-specific genes. Furthermore, at
      least twenty-eight of the top fifty (56%) candidates (or their vertebrate
      orthologs) were previously reported to have a nephron-specific expression
      pattern. Our analysis of E14.5 expression data yielded 41 candidate genes that
      are up-regulated in the control kidneys compared to the conditional mutants.
      Three of them are related to the Notch signaling pathway that is known to be
      important in cell fate determination and nephron patterning. CONCLUSION:
      Therefore, we demonstrate that Lim1 conditional mutant kidneys serve as a novel
      tissue source for comprehensive expression studies and provide a means to
      identify nephron-specific genes.

PMID- 16464247
TI  - Zn, Cu, Cd and Hg binding to metallothioneins in harbour porpoises Phocoena
      phocoena from the southern North Sea.
AB  - BACKGROUND: Harbour porpoises Phocoena phocoena from the southern North Sea are
      known to display high levels of Zn and Hg in their tissues linked to their
      nutritional status (emaciation). The question arises regarding a potential role
      of metallothioneins (MTs) with regard to these high metal levels. In the present
      study, metallothionein detection and associated Zn, Cd, Cu and Hg concentrations
      were investigated in the liver and kidney of 14 harbour porpoises collected along
      the Belgian coast. RESULTS: Metallothioneins seemed to play a key role in
      essential metal homeostasis, as they were shown to bind 50% of the total hepatic
      Zn and 36% of the total hepatic Cu concentrations. Renal MTs also participated in
      Cd detoxification, as they were shown to bind 56% of the total renal Cd. Hg was
      mainly found in the insoluble fraction of both liver and kidney. Concomitant
      increases in total Zn concentration and Zn bound to MTs were observed in the
      liver, whereas Zn concentration bound to high molecular weight proteins remained
      constant. Cu, Zn and Cd were accumulated preferentially in the MT fraction and
      their content in this fraction increased with the amount in the hepatocytosol.
      CONCLUSION: MTs have a key role in Zn and Cu homeostasis in harbour porpoises. We
      demonstrated that increasing hepatic Zn concentration led to an increase in Zn
      linked to MTs, suggesting that these small proteins take over the Zn overload
      linked to the poor body condition of debilitated harbour porpoises.

PMID- 16464249
TI  - A MEDLINE categorization algorithm.
AB  - BACKGROUND: Categorization is designed to enhance resource description by
      organizing content description so as to enable the reader to grasp quickly and
      easily what are the main topics discussed in it. The objective of this work is to
      propose a categorization algorithm to classify a set of scientific articles
      indexed with the MeSH thesaurus, and in particular those of the MEDLINE
      bibliographic database. In a large bibliographic database such as MEDLINE,
      finding materials of particular interest to a specialty group, or relevant to a
      particular audience, can be difficult. The categorization refines the retrieval
      of indexed material. In the CISMeF terminology, metaterms can be considered as
      super-concepts. They were primarily conceived to improve recall in the CISMeF
      quality-controlled health gateway. METHODS: The MEDLINE categorization algorithm
      (MCA) is based on semantic links existing between MeSH terms and metaterms on the
      one hand and between MeSH subheadings and metaterms on the other hand. These
      links are used to automatically infer a list of metaterms from any MeSH
      term/subheading indexing. Medical librarians manually select the semantic links.
      RESULTS: The MEDLINE categorization algorithm lists the medical specialties
      relevant to a MEDLINE file by decreasing order of their importance. The MEDLINE
      categorization algorithm is available on a Web site. It can run on any MEDLINE
      file in a batch mode. As an example, the top 3 medical specialties for the set of
      60 articles published in BioMed Central Medical Informatics & Decision Making,
      which are currently indexed in MEDLINE are: information science, organization and
      administration and medical informatics. CONCLUSION: We have presented a MEDLINE
      categorization algorithm in order to classify the medical specialties addressed
      in any MEDLINE file in the form of a ranked list of relevant specialties. The
      categorization method introduced in this paper is based on the manual indexing of
      resources with MeSH (terms/subheadings) pairs by NLM indexers. This algorithm may
      be used as a new bibliometric tool.

PMID- 16464250
TI  - Are osteoporotic fractures being adequately investigated? A questionnaire of GP &
      orthopaedic surgeons.
AB  - BACKGROUND: To investigate the current practice of Orthopaedic Surgeons & General
      Practitioners (GP) when presented with patients who have a fracture, with
      possible underlying Osteoporosis. METHODS: Questionnaires were sent to 140 GPs
      and 140 Orthopaedic Surgeons. The participants were asked their routine clinical
      practice with regard to investigation of underlying osteoporosis in 3 clinical
      scenarios. 55 year old lady with a low trauma Colles fracture. 60 year old lady
      with a vertebral wedge fracture. 70 year old lady with a low trauma neck of femur
      fracture. RESULTS: Most doctors agreed that patients over 50 years old with low
      trauma fractures required investigation for osteoporosis, however, most surgeons
      (56%, n = 66) would discharge patients with low trauma Colles fracture without
      requesting or initiating investigation for osteoporosis. Most GPs (67%, n = 76)
      would not investigate a similar patient for osteoporosis, unless prompted by the
      Orthopaedic Surgeon or patient. More surgeons (71%, n= 83) and GPs (64%, n = 72)
      would initiate investigations for osteoporosis in a vertebral wedge fracture, but
      few surgeons (35%, n = 23) would investigate a neck of femur fracture patient
      after orthopaedic treatment. CONCLUSION: Most doctors know that fragility
      fractures in patients over 50 years old require investigation for Osteoporosis;
      however, a large population of patients with osteoporotic fractures are not being
      given the advantages of secondary prevention.

PMID- 16464248
TI  - A methodology for the structural and functional analysis of signaling and
      regulatory networks.
AB  - BACKGROUND: Structural analysis of cellular interaction networks contributes to a
      deeper understanding of network-wide interdependencies, causal relationships, and
      basic functional capabilities. While the structural analysis of metabolic
      networks is a well-established field, similar methodologies have been scarcely
      developed and applied to signaling and regulatory networks. RESULTS: We propose
      formalisms and methods, relying on adapted and partially newly introduced
      approaches, which facilitate a structural analysis of signaling and regulatory
      networks with focus on functional aspects. We use two different formalisms to
      represent and analyze interaction networks: interaction graphs and (logical)
      interaction hypergraphs. We show that, in interaction graphs, the determination
      of feedback cycles and of all the signaling paths between any pair of species is
      equivalent to the computation of elementary modes known from metabolic networks.
      Knowledge on the set of signaling paths and feedback loops facilitates the
      computation of intervention strategies and the classification of compounds into
      activators, inhibitors, ambivalent factors, and non-affecting factors with
      respect to a certain species. In some cases, qualitative effects induced by
      perturbations can be unambiguously predicted from the network scheme. Interaction
      graphs however, are not able to capture AND relationships which do frequently
      occur in interaction networks. The consequent logical concatenation of all the
      arcs pointing into a species leads to Boolean networks. For a Boolean
      representation of cellular interaction networks we propose a formalism based on
      logical (or signed) interaction hypergraphs, which facilitates in particular a
      logical steady state analysis (LSSA). LSSA enables studies on the logical
      processing of signals and the identification of optimal intervention points
      (targets) in cellular networks. LSSA also reveals network regions whose
      parametrization and initial states are crucial for the dynamic behavior. We have
      implemented these methods in our software tool CellNetAnalyzer (successor of
      FluxAnalyzer) and illustrate their applicability using a logical model of T-Cell
      receptor signaling providing non-intuitive results regarding feedback loops,
      essential elements, and (logical) signal processing upon different stimuli.
      CONCLUSION: The methods and formalisms we propose herein are another step towards
      the comprehensive functional analysis of cellular interaction networks. Their
      potential, shown on a realistic T-cell signaling model, makes them a promising
      tool.

PMID- 16464251
TI  - PathSys: integrating molecular interaction graphs for systems biology.
AB  - BACKGROUND: The goal of information integration in systems biology is to combine
      information from a number of databases and data sets, which are obtained from
      both high and low throughput experiments, under one data management scheme such
      that the cumulative information provides greater biological insight than is
      possible with individual information sources considered separately. RESULTS: Here
      we present PathSys, a graph-based system for creating a combined database of
      networks of interaction for generating integrated view of biological mechanisms.
      We used PathSys to integrate over 14 curated and publicly contributed data
      sources for the budding yeast (S. cerevisiae) and Gene Ontology. A number of
      exploratory questions were formulated as a combination of relational and graph
      based queries to the integrated database. Thus, PathSys is a general-purpose,
      scalable, graph-data warehouse of biological information, complete with a graph
      manipulation and a query language, a storage mechanism and a generic data
      importing mechanism through schema-mapping. CONCLUSION: Results from several test
      studies demonstrate the effectiveness of the approach in retrieving biologically
      interesting relations between genes and proteins, the networks connecting them,
      and of the utility of PathSys as a scalable graph-based warehouse for interaction
      network integration and a hypothesis generator system. The PathSys's client
      software, named BiologicalNetworks, developed for navigation and analyses of
      molecular networks, is available as a Java Web Start application at
      http://brak.sdsc.edu/pub/BiologicalNetworks.

PMID- 16464253
TI  - FastGroupII: a web-based bioinformatics platform for analyses of large 16S rDNA
      libraries.
AB  - BACKGROUND: High-throughput sequencing makes it possible to rapidly obtain
      thousands of 16S rDNA sequences from environmental samples. Bioinformatic tools
      for the analyses of large 16S rDNA sequence databases are needed to
      comprehensively describe and compare these datasets. RESULTS: FastGroupII is a
      web-based bioinformatics platform to dereplicate large 16S rDNA libraries.
      FastGroupII provides users with the option of four different dereplication
      methods, performs rarefaction analysis, and automatically calculates the Shannon
      Wiener Index and Chao1. FastGroupII was tested on a set of 16S rDNA sequences
      from coral-associated Bacteria. The different grouping algorithms produced
      similar, but not identical, results. This suggests that 16S rDNA datasets need to
      be analyzed in multiple ways when being used for community ecology studies.
      CONCLUSION: FastGroupII is an effective bioinformatics tool for the trimming and
      dereplication of 16S rDNA sequences. Several standard diversity indices are
      calculated, and the raw sequences are prepared for downstream analyses.

PMID- 16464252
TI  - Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic
      virulence factors.
AB  - BACKGROUND: It has been recently reported that major pathogens Staphylococcus
      aureus and Pseudomonas aeruginosa accelerate a normal process of cell surface
      syndecan-1 (Synd1) ectodomain shedding as a mechanism of host damage due to the
      production of shedding-inducing virulence factors. We tested if acceleration of
      Synd1 shedding takes place in vitro upon treatment of epithelial cells with B.
      anthracis hemolysins, as well as in vivo during anthrax infection in mice.
      RESULTS: The isolated anthrax hemolytic proteins AnlB (sphingomyelinase) and AnlO
      (cholesterol-binding pore-forming factor), as well as ClnA (B. cereus homolog of
      B. anthracis phosphatidyl choline-preferring phospholipase C) cause accelerated
      shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial
      barrier integrity within a few hours. In comparison with hemolysins in a similar
      range of concentrations, anthrax lethal toxin (LT) also accelerates shedding
      albeit at slower rate. Individual components of LT, lethal factor and protective
      antigen are inactive with regard to shedding. Inhibition experiments favor a
      hypothesis that activities of tested bacterial shedding inducers converge on the
      stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading
      to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK
      signaling pathways, while JNK pathway seems to be irrelevant to accelerated
      shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged
      with Bacillus anthracis (Sterne) spores. Elevated levels of shed ectodomain are
      readily detectable in circulation after 24 h. CONCLUSION: The concerted
      acceleration of shedding by several virulence factors could represent a new
      pathogenic mechanism contributing to disruption of epithelial or endothelial
      integrity, hemorrhage, edema and abnormal cell signaling during anthrax
      infection.

PMID- 16464254
TI  - Assessment of Plasmodium falciparum resistance to ferroquine (SSR97193) in field
      isolates and in W2 strain under pressure.
AB  - BACKGROUND: Ferroquine (FQ), or SSR97193, is a novel antimalarial drug currently
      in phase I clinical trials. FQ is a unique organometallic compound designed to
      overcome the chloroquine (CQ) resistance problem. FQ revealed to be equally
      active on CQ-sensitive and CQ-resistant Plasmodium falciparum laboratory strains
      and field isolates. FQ is also curative on rodent malaria parasites. As FQ will
      be tested in patients, the potential for resistance to this drug was evaluated.
      METHODS: The relationship between CQ-resistant transporter gene genotype and
      susceptibility to FQ were studied in 33 Cambodian P. falciparum field isolates
      previously studied for their in vitro response to CQ. In parallel, the ability of
      the CQ-resistant strain W2, to become resistant to FQ under drug pressure was
      assessed. RESULTS: The IC50 values for FQ in field isolates were found to be
      unrelated to mutations occurring in the P. falciparum chloroquine resistance
      transporter (PfCRT) or to the level of expression of the corresponding mRNA. In
      vitro, under a drug pressure of 100 nM of FQ, transient survival was observed in
      only one of two experiments. CONCLUSION: Field isolates studies and experimental
      drug pressure experiments showed that FQ overcomes CQ resistance, which
      reinforces the potential of this compound as a new antimalarial drug.

PMID- 16464255
TI  - Cross-sectional relationship between physical fitness components and functional
      performance in older persons living in long-term care facilities.
AB  - BACKGROUND: The age-related deterioration of physiological capacities such as
      muscle strength and balance is associated with increased dependence.
      Understanding the contribution of physical fitness components to functional
      performance facilitates the development of adequate exercise interventions aiming
      at preservation of function and independence of older people. The aim of the
      study was to investigate the relationship between physical fitness components and
      functional performance in older people living in long-term care facilities.
      METHODS: Design cross-sectional study. Subjects 226 persons living in long-term
      care facilities (mean age: 81.6 +/- 5.6). Outcome measures Physical fitness and
      functional performance were measured by performance-based tests. RESULTS: Knee
      and elbow extension strength were significantly higher in men (difference = 44.5
      and 50.0 N, respectively), whereas women were more flexible (difference sit &
      reach test = 7.2 cm). Functional performance was not significantly different
      between the genders. In men, motor coordination (eye-hand coordination) and
      measures of strength were the main contributors to functional performance,
      whereas in women flexibility (sit and reach test) and motor coordination (tandem
      stance and eye-hand coordination) played a major role. CONCLUSION: The results of
      this study show that besides muscle strength, fitness components such as
      coordination and flexibility are associated with functional performance of older
      people living in long-term care facilities. This suggests that men and women
      living in long-term care facilities, differ considerably concerning the fitness
      factors contributing to functional performance. Women and men may, therefore,
      need exercise programs emphasizing different fitness aspects in order to improve
      functional performance.

PMID- 16464256
TI  - Integrated analysis of gene expression by Association Rules Discovery.
AB  - BACKGROUND: Microarray technology is generating huge amounts of data about the
      expression level of thousands of genes, or even whole genomes, across different
      experimental conditions. To extract biological knowledge, and to fully understand
      such datasets, it is essential to include external biological information about
      genes and gene products to the analysis of expression data. However, most of the
      current approaches to analyze microarray datasets are mainly focused on the
      analysis of experimental data, and external biological information is
      incorporated as a posterior process. RESULTS: In this study we present a method
      for the integrative analysis of microarray data based on the Association Rules
      Discovery data mining technique. The approach integrates gene annotations and
      expression data to discover intrinsic associations among both data sources based
      on co-occurrence patterns. We applied the proposed methodology to the analysis of
      gene expression datasets in which genes were annotated with metabolic pathways,
      transcriptional regulators and Gene Ontology categories. Automatically extracted
      associations revealed significant relationships among these gene attributes and
      expression patterns, where many of them are clearly supported by recently
      reported work. CONCLUSION: The integration of external biological information and
      gene expression data can provide insights about the biological processes
      associated to gene expression programs. In this paper we show that the proposed
      methodology is able to integrate multiple gene annotations and expression data in
      the same analytic framework and extract meaningful associations among
      heterogeneous sources of data. An implementation of the method is included in the
      Engene software package.

PMID- 16464257
TI  - An extremely rich repertoire of bursting patterns during the development of
      cortical cultures.
AB  - BACKGROUND: We have collected a comprehensive set of multi-unit data on
      dissociated cortical cultures. Previous studies of the development of the
      electrical activity of dissociated cultures of cortical neurons each focused on
      limited aspects of its dynamics, and were often based on small numbers of
      observed cultures. We followed 58 cultures of different densities--3000 to 50,000
      neurons on areas of 30 to 75 mm2--growing on multi-electrode arrays (MEAs) during
      the first five weeks of their development. RESULTS: Plating density had a
      profound effect on development. While the aggregate spike detection rate scaled
      linearly with density, as expected from the number of cells in proximity to
      electrodes, dense cultures started to exhibit bursting behavior earlier in
      development than sparser cultures. Analysis of responses to electrical
      stimulation suggests that axonal outgrowth likewise occurred faster in dense
      cultures. After two weeks, the network activity was dominated by population
      bursts in most cultures. In contrast to previous reports, development continued
      with changing burst patterns throughout the observation period. Burst patterns
      were extremely varied, with inter-burst intervals between 1 and 300 s, different
      amounts of temporal clustering of bursts, and different firing rate profiles
      during bursts. During certain stages of development bursts were organized into
      tight clusters with highly conserved internal structure. CONCLUSION: Dissociated
      cultures of cortical cells exhibited a much richer repertoire of activity
      patterns than previously reported. Except for the very sparsest cultures, all
      cultures exhibited globally synchronized bursts, but bursting patterns changed
      over the course of development, and varied considerably between preparations.
      This emphasizes the importance of using multiple preparations--not just multiple
      cultures from one preparation--in any study involving neuronal cultures. These
      results are based on 963 half-hour-long recordings. To encourage further
      investigation of the rich range of behaviors exhibited by cortical cells in
      vitro, we are making the data available to other researchers, together with
      Matlab code to facilitate access.

PMID- 16464258
TI  - Indicators of breast cancer severity and appropriateness of surgery based on
      hospital administrative data in the Lazio Region, Italy.
AB  - BACKGROUND: Administrative data can serve as an easily available source for
      epidemiological and evaluation studies. The aim of this study is to evaluate the
      use of hospital administrative data to determine breast cancer severity and the
      appropriateness of surgical treatment. METHODS: the study population consisted of
      398 patients randomly selected from a cohort of women hospitalized for first-time
      breast cancer surgery in the Lazio Region, Italy. Tumor severity was defined in
      three different ways: 1) tumor size; 2) clinical stage (TNM); 3) severity
      indicator based on HIS data (SI). Sensitivity, specificity, and positive
      predictive value (PPV) of the severity indicator in evaluating appropriateness of
      surgery were calculated. The accuracy of HIS data was measured using Kappa
      statistic. RESULTS: Most of 387 cases were classified as T1 and T2 (tumor size),
      more than 70% were in stage I or II and the SI classified 60% of cases in medium
      low category. Variation from guidelines indications identified under and over
      treatments. The accuracy of the SI to predict under-treatment was relatively good
      (58% of all procedures classified as under-treatment using pT where also
      classified as such using SI), and even greater predicting over-treatment (88.2%
      of all procedures classified as over treatment using pT where also classified as
      such using SI). Agreement between clinical chart and hospital discharge reports
      was K = 0.35. CONCLUSION: Our findings suggest that administrative data need to
      be used with caution when evaluating surgical appropriateness, mainly because of
      the limited ability of SI to predict tumor size and the questionable quality of
      HIS data as observed in other studies.

PMID- 16464259
TI  - The GCC repeat length in the 5'UTR of MRP1 gene is polymorphic: a functional
      characterization of its relevance for cystic fibrosis.
AB  - BACKGROUND: Among the members of the ATP binding cassette transporter
      superfamily, MRPs share the closest homology with the CFTR protein, which is
      defective in CF disease. MRP1 has been proposed as a potential modifier gene
      and/or as novel target for pharmacotherapy of CF to explain the clinical benefits
      observed in some CF patients treated with the macrolide AZM. The 5'UTR of the
      MRP1 gene contains a GCC triplet repeat that could represent a polymorphic site
      and affect the activity of the promoter. METHODS: The MRP1 5' flanking region was
      amplified by PCR from 36 CF patients and 100 non-CF subjects and the number of
      GCC triplets of each allele was determined by sequence and electrophoretic
      analysis. We performed gene reporter studies in CF airway epithelial cells
      16HBE14o-AS3, in basal conditions and in the presence of AZM. RESULTS: We found
      that the GCC repeat is polymorphic, ranging from 7 to 14 triplets either in CF or
      in non-CF subjects. Our data are preliminary and have to be confirmed on a larger
      population of CF subjects. The transcriptional activity of the proximal MRP1 5'
      regulatory region revealed no statistically significant correlations between the
      number of repeats and treatment with AZM. CONCLUSION: We identified a novel
      polymorphism in the 5'UTR of MRP1 gene that provides multiple alleles in a gene
      relevant for multidrug resistance as well as for CF, determining that this region
      is transcriptionally active and that this activity does not appear to be
      influenced by AZM treatment.

PMID- 16464261
TI  - Polyphyly of the hawk genera Leucopternis and Buteogallus (Aves, Accipitridae):
      multiple habitat shifts during the Neotropical buteonine diversification.
AB  - BACKGROUND: The family Accipitridae (hawks, eagles and Old World vultures)
      represents a large radiation of predatory birds with an almost global
      distribution, although most species of this family occur in the Neotropics.
      Despite great morphological and ecological diversity, the evolutionary
      relationships in the family have been poorly explored at all taxonomic levels.
      Using sequences from four mitochondrial genes (12S, ATP8, ATP6, and ND6), we
      reconstructed the phylogeny of the Neotropical forest hawk genus Leucopternis and
      most of the allied genera of Neotropical buteonines. Our goals were to infer the
      evolutionary relationships among species of Leucopternis, estimate their
      relationships to other buteonine genera, evaluate the phylogenetic significance
      of the white and black plumage patterns common to most Leucopternis species, and
      assess general patterns of diversification of the group with respect to species'
      affiliations with Neotropical regions and habitats. RESULTS: Our molecular
      phylogeny for the genus Leucopternis and its allies disagrees sharply with
      traditional taxonomic arrangements for the group, and we present new hypotheses
      of relationships for a number of species. The mtDNA phylogenetic trees derived
      from analysis of the combined data posit a polyphyletic relationship among
      species of Leucopternis, Buteogallus and Buteo. Three highly supported clades
      containing Leucopternis species were recovered in our phylogenetic
      reconstructions. The first clade consisted of the sister pairs L. lacernulatus
      and Buteogallus meridionalis, and Buteogallus urubitinga and Harpyhaliaetus
      coronatus, in addition to L. schistaceus and L. plumbeus. The second clade
      included the sister pair Leucopternis albicollis and L. occidentalis as well as
      L. polionotus. The third lineage comprised the sister pair L. melanops and L.
      kuhli, in addition to L. semiplumbeus and Buteo buteo. According to our results,
      the white and black plumage patterns have evolved at least twice in the group.
      Furthermore, species found to the east and west of the Andes (cis-Andean and
      trans-Andean, respectively) are not reciprocally monophyletic, nor are forest and
      non-forest species. CONCLUSION: The polyphyly of Leucopternis, Buteogallus and
      Buteo establishes a lack of concordance of current Accipitridae taxonomy with the
      mtDNA phylogeny for the group, and points to the need for further phylogenetic
      analysis at all taxonomic levels in the family as also suggested by other recent
      analyses. Habitat shifts, as well as cis- and trans-Andean disjunctions, took
      place more than once during buteonine diversification in the Neotropical region.
      Overemphasis of the black and white plumage patterns has led to questionable
      conclusions regarding the relationships of Leucopternis species, and suggests
      more generally that plumage characters should be used with considerable caution
      in the taxonomic evaluation of the Accipitridae.

PMID- 16464262
TI  - Effort-reward imbalance at work and the co-occurrence of lifestyle risk factors:
      cross-sectional survey in a sample of 36,127 public sector employees.
AB  - BACKGROUND: In occupational life, a mismatch between high expenditure of effort
      and receiving few rewards may promote the co-occurrence of lifestyle risk
      factors, however, there is insufficient evidence to support or refute this
      hypothesis. The aim of this study is to examine the extent to which the
      dimensions of the Effort-Reward Imbalance (ERI) model--effort, rewards and ERI-
      are associated with the co-occurrence of lifestyle risk factors. METHODS: Based
      on data from the Finnish Public Sector Study, cross-sectional analyses were
      performed for 28,894 women and 7233 men. ERI was conceptualized as a ratio of
      effort and rewards. To control for individual differences in response styles,
      such as a personal disposition to answer negatively to questionnaires,
      occupational and organizational-level ecological ERI scores were constructed in
      addition to individual-level ERI scores. Risk factors included current smoking,
      heavy drinking, body mass index > or =25 kg/m2, and physical inactivity.
      Multinomial logistic regression models were used to estimate the likelihood of
      having one risk factor, two risk factors, and three or four risk factors. The
      associations between ERI and single risk factors were explored using binary
      logistic regression models. RESULTS: After adjustment for age, socioeconomic
      position, marital status, and type of job contract, women and men with high
      ecological ERI were 40% more likely to have simultaneously > or =3 lifestyle risk
      factors (vs. 0 risk factors) compared with their counterparts with low ERI. When
      examined separately, both low ecological effort and low ecological rewards were
      also associated with an elevated prevalence of risk factor co-occurrence. The
      results obtained with the individual-level scores were in the same direction. The
      associations of ecological ERI with single risk factors were generally less
      marked than the associations with the co-occurrence of risk factors. CONCLUSION:
      This study suggests that a high ratio of occupational efforts relative to rewards
      may be associated with an elevated risk of having multiple lifestyle risk
      factors. However, an unexpected association between low effort and a higher
      likelihood of risk factor co-occurrence as well as the absence of data on
      overcommitment (and thereby a lack of full test of the ERI model) warrant caution
      in regard to the extent to which the entire ERI model is supported by our
      evidence.

PMID- 16464263
TI  - The complete mitochondrial genome of the enigmatic bigheaded turtle
      (Platysternon): description of unusual genomic features and the reconciliation of
      phylogenetic hypotheses based on mitochondrial and nuclear DNA.
AB  - BACKGROUND: The big-headed turtle (Platysternon megacephalum) from east Asia is
      the sole living representative of a poorly-studied turtle lineage
      (Platysternidae). It has no close living relatives, and its phylogenetic position
      within turtles is one of the outstanding controversies in turtle systematics.
      Platysternon was traditionally considered to be close to snapping turtles
      (Chelydridae) based on some studies of its morphology and mitochondrial (mt) DNA,
      however, other studies of morphology and nuclear (nu) DNA do not support that
      hypothesis. RESULTS: We sequenced the complete mt genome of Platysternon and the
      nearly complete mt genomes of two other relevant turtles and compared them to
      turtle mt genomes from the literature to form the largest molecular dataset used
      to date to address this issue. The resulting phylogeny robustly rejects the
      placement of Platysternon with Chelydridae, but instead shows that it is a member
      of the Testudinoidea, a diverse, nearly globally-distributed group that includes
      pond turtles and tortoises. We also discovered that Platysternon mtDNA has large
      scale gene rearrangements and possesses two, nearly identical, control regions,
      features that distinguish it from all other studied turtles. CONCLUSION: Our
      study robustly determines the phylogenetic placement of Platysternon and provides
      a well-resolved outline of major turtle lineages, while demonstrating the
      significantly greater resolving power of comparing large amounts of mt sequence
      over that of short fragments. Earlier phylogenies placing Platysternon with
      chelydrids required a temporal gap in the fossil record that is now unnecessary.
      The duplicated control regions and gene rearrangements of the Platysternon mtDNA
      probably resulted from the duplication of part of the genome and then the
      subsequent loss of redundant genes. Although it is possible that having two
      control regions may provide some advantage, explaining why the control regions
      would be maintained while some of the duplicated genes were eroded, examples of
      this are rare. So far, duplicated control regions have been reported for mt
      genomes from just 12 clades of metazoans, including Platysternon.

PMID- 16464264
TI  - Identifying barriers to participation in prophylactic HIV-1 vaccine trials.

PMID- 16464265
TI  - Hepatitis C transmission -- where are we now?
AB  - Since the discovery of hepatitis C virus (HCV) in 1989, there has been much
      debate regarding its potential modes of transmission particularly as only about
      half of the reported cases of acute HCV have a defined parenteral exposure. It
      has been clearly established that blood-blood contact is important in its
      transmission, but the question of sexual transmission has caused more controversy
      with studies producing conflicting evidence. The objective of this review was to
      examine the current evidence on all reported routes of transmission of hepatitis
      C with particular attention to sexual transmission in men having sex with men
      (MSM) and HIV-positive individuals. We conducted PubMed searches using keywords
      hepatitis C, transmission, sexual, HIV, MSM, mother to child, haemophilia,
      intravenous drug use, tattooing and skin piercing. The bibliographies in articles
      identified were also searched.

PMID- 16464267
TI  - UK Guideline for the use of post-exposure prophylaxis for HIV following sexual
      exposure.
AB  - We present the British Association for Sexual Health and HIV (BASHH) guidelines
      for post-exposure prophylaxis after sexual exposure (PEPSE) to HIV. This document
      includes a review of the current data to support the use of PEPSE, considers how
      to calculate the risks of HIV infection after a potential exposure, and provides
      recommendations on when PEPSE would and would not be considered. Other areas
      included are the possible impact on sexual behaviour, cost-effectiveness, and
      issues relating to service provision. Throughout the document, consideration is
      given to the place of PEPSE within the broader context of HIV prevention
      strategies and sexual health.

PMID- 16464268
TI  - Consequences of HIV testing without consent.
AB  - The objective of this study is to explore the HIV-infected individuals'
      experience with HIV testing, counselling, disclosure of diagnosis and subsequent
      life events following diagnosis. The method used is a questionnaire survey of 340
      consecutive HIV-positive victims, seen in two health institutions in southeast
      Nigeria within a one-year-period, November 2003 to October 2004. Three hundred
      and twenty respondents answered the questionnaire, 121 were men and 199 women,
      with 79% in the age range 20-39 years. Most respondents had known their HIV
      status for 3.2 (+/-1.1) years and the majority are in the lower social class.
      About 80% reported that their consent for HIV test was not asked for, resulting
      in feelings of fear, disbelief, shock and embarrassment on learning about their
      HIV status. Despite the initial reaction to the diagnosis, majority (81.9%)
      expressed satisfaction with the pattern of disclosure of diagnosis. There was
      some reluctance to inform spouse/partner of the diagnosis especially among
      asymptomatic, unmarried, childless or divorced victims. A serodiscordant couple
      resulted in mistrust and increased incidence of abandonment. Apart from
      spouse/partner the respondents are more likely to inform their siblings of the
      diagnosis than parents, children or friends. Despite being supportive, the
      respondents are more likely to suffer more neglect from siblings than their
      spouse (P<0.05) but the risk of being abandoned was more with the spouse than
      with siblings (P<0.05). Only 32.6% of the 129 respondents on antiretroviral
      therapy are regular with it mainly because of cost and non-availability of drugs.
      Default in treatment was more evident among the unmarried, those with low
      educational status and treatment with antiretroviral drugs for more than two
      years. Proper pre- and post-test counselling, promotion of behavioural change
      among the society about HIV/AIDS and provision of support and cost-effective care
      for HIV victims is advocated.

PMID- 16464269
TI  - Evaluation of time for non-GU medicine physicians to diagnose HIV infection in
      patients presenting with HIV-related illnesses.
AB  - Some individuals with HIV in the UK are only diagnosed when they are admitted to
      hospitals with AIDS-defining illnesses. Early diagnosis and intervention are
      important to reduce the morbidity and mortality of HIV infection. Delays in
      diagnosing HIV infection may be expected to result in an increased risk of
      disease progression and complications. This retrospective cohort study was
      conducted between January 2002 and December 2003. Two hundred and nineteen new
      HIV infections were diagnosed in three hospitals in the south of England during
      the study period. Of these, 58 patients (35M, 23F) were diagnosed in non-GUM
      settings. The mean age was 39 years. Over 70% of the diagnoses were made within
      seven days. Eight percent of the diagnoses were made more than 50 days from the
      time of first presentation. The surgeons appeared no slower at diagnosing HIV
      infection in their patients than medical specialties. Late diagnosis of HIV
      infection remains a significant problem. HIV infection should be considered as
      part of the differential diagnoses to ensure early diagnosis and intervention.

PMID- 16464270
TI  - Racial and ethnic differences in knowledge and willingness to participate in HIV
      vaccine trials in an urban population in the Southeastern US.
AB  - Racial/ethnic minorities in the Southeastern USA are disproportionately affected
      by HIV, and would benefit from a preventive vaccine. We conducted a cross
      sectional survey of 220 community college students in Atlanta to evaluate
      racial/ethnic differences in knowledge and willingness to participate in HIV
      vaccine trials. Willingness to participate did not differ by race/ethnicity, age,
      or gender, and was not associated with knowledge. African-Americans and Asians
      were more likely than Whites to: believe that an HIV vaccine exists, but is being
      withheld from the public; believe that AIDS was caused by a government
      conspiracy; feel that having other participants and investigators of their ethnic
      background in the trial was important. Misconceptions regarding HIV vaccines are
      common and differ by race/ethnicity. However, willingness to participate was not
      associated with knowledge or race/ethnicity. Efforts to increase participation
      should address the ethnic diversity of the trial personnel, and education to
      eliminate misconceptions about HIV vaccines and trials.

PMID- 16464271
TI  - Sexual behaviours of HIV-seropositive men and women following release from
      prison.
AB  - Twenty-five percent of the US HIV-infected population is released from a prison
      or jail each year. As the extent of risky sexual behaviours after prison release
      is largely unknown, we interviewed a cohort (n = 64) of HIV-infected, recently
      released (mean 45 days, SD 28) prisoners about their current sexual risk
      behaviours. Almost half (47%, n = 64) of the released prisoners reported sexual
      activity after release, mostly with regular partners. Although 26% (n = 27)
      reported engaging in unprotected sexual activity with their regular partners,
      none (n = 4) reported unprotected sex with their non-regular partners.
      Furthermore, 33% percent (n = 15) of the releasees with regular partners reported
      engaging in unprotected sex with HIV-seronegative partners. These results suggest
      that regular partners of HIV-infected prison releasees are at risk of acquiring
      HIV infection, and secondary risk-reduction strategies are needed for HIV
      infected prison releasees.

PMID- 16464272
TI  - Delivering results to clients: a question of satisfying needs or desires?
AB  - Demand for genitourinary (GU) medicine services is outstripping supply. Improving
      efficiency can modulate the supply side of the equation, e.g. decreasing the
      number of clients having to return for their results. This survey explored how
      clients at two central London GU medicine clinics would like to receive their
      results and their views were reflected against what was offered by London GU
      medicine clinics. There was a significant difference between the result delivery
      services that the clients wanted and what the clinics provided (P <0.0001,
      chi(2)). Of the clients, 92% wanted to know their results regardless of outcome
      whereas 22% of London clinics would only inform clients of positive results. This
      study questions the importance and feasibility of patient choice, an important
      aspect of the National Strategy for Sexual Health and HIV. Clinics may not
      individually be able to provide choice but between them, they do provide a wide
      range of alternatives for the client.

PMID- 16464273
TI  - Screening HIV-positive pregnant women for antiretroviral therapy: utility of self
      reported symptoms.
AB  - In developing countries, Mother-to-Child Transmission-Plus programmes propose to
      identify lifelong antiretroviral therapy (ART)-eligible women during antenatal
      care. Identification using AIDS-related symptoms is the most feasible screening
      procedure in resource-limited settings. It is not known if symptomatology in
      pregnant women is correlated with clinical criteria for ART initiation based on
      CD(4)+ cell count or HIV-1 viral load. In this population of HIV-positive
      pregnant women from Rakai District, Uganda, 8-23% were eligible for treatment by
      CD(4)+ cell count criteria, and <1% met WHO staging criteria for AIDS. Using one
      or more symptoms to predict CD(4)+ cell count <350 cells/mm(3), sensitivity was
      100%, specificity 11%, positive predictive value (PPV) 25%, and negative
      predictive value (NPV) 100%. When using one or more symptoms to predict viral
      load > or =100,000 cps/mL, sensitivity was 100%, specificity 10%, PPV 6%, and NPV
      100%. Initiation of treatment based on self-reported symptoms will over-treat
      because the majority of pregnant women with symptoms would not be eligible for
      treatment under current guidelines, but asymptomatic pregnant women are unlikely
      to require ART.

PMID- 16464274
TI  - Clinical illness as a marker for initiation of HIV antiretroviral therapy in a
      rural setting, Rakai, Uganda.
AB  - The aim of this study is to assess whether HIV-related illness and World Health
      Organization (WHO) clinical stage can be used to guide initiation of
      antiretroviral therapy (ART) in rural Rakai District, Uganda. A retrospective
      cohort analysis of 910 HIV-seroprevalent individuals randomly sampled from a
      community cohort was conducted. The associations between HIV-related clinical
      illness and HIV viral loads >55,000 copies/mL and death were evaluated as a guide
      for initiation of ART. Reporting one or more HIV-related illnesses was associated
      with high specificity for identifying HIV viral load >55,000 copies/mL and
      predicting death within 30 months. There were more deaths in those with one
      symptom at baseline (16.3%) and two or more symptoms (25.0%) than in those
      reporting no symptoms (9.6%; P = 0.001).HIV-related illness and WHO stage
      predicted disease progression. The specificity of clinical illness to predict
      viral load >55,000 copies/mL was high and could be used to rule in HIV disease
      requiring ART.

PMID- 16464275
TI  - Client acceptability of the use of computers in a sexual health clinic.
AB  - Computers in sexual health medicine largely remain provider-centred for use in
      client care, data collection, administration and education. As a formative study
      for further work we undertook a cross-sectional survey of 679 consecutive new
      clients attending Melbourne Sexual Health clinic (MSHC) between 9 September 2002
      and 15 October 2002 to establish client familiarity and experience with computers
      and acceptance of computer use in the clinic. A response rate of 616/679 (91%)
      was achieved. Important findings were: 1. 491/612 (80%) participants reported
      experience with a personal computer. 2. The majority 488/609 (80%) of clients
      expected computer technologies to be used in the clinic. 3. The proportion of
      clients not willing to supply their registration, general health or sexual
      behaviour details using a computer was 9%, 7% and 21%, respectively. 4. Clients
      assessed as being at higher risk of acquiring a sexually transmitted infection
      were no more reluctant than others to provide their details using a computer
      assisted self-interview.

PMID- 16464276
TI  - Genital shedding of herpes simplex virus type 2 in childbearing-aged and pregnant
      women living in Gabon.
AB  - The prevalence of genital shedding of herpes simplex virus (HSV)-2 and related
      risk factors was evaluated in a prospective population of 355 women attending the
      Maternity Josephine Bongo, in Libreville, Gabon. We found a high prevalence (66%)
      of HSV-2 seropositivity, with a high proportion, 14%, of women harbouring HSV-2
      DNA shedding in their genital secretions. HSV-2 genital shedding was positively
      associated with previous episodes of genital blisters, current genital ulcer,
      current genital blister, HIV seropositivity and HSV-2 seropositivity. The high
      prevalence of HSV-2 in childbearing-aged population indicates that young women
      living in Gabon are at high risk for HIV acquisition in HIV-seronegative women
      sexually exposed to HIV, for HIV transmission in HIV-infected women co-infected
      by HSV-2 and finally for HSV-2 vertical transmission during pregnancy.

PMID- 16464277
TI  - Which measure of contact tracing performance? -- using audit as the evidence
      base.
AB  - Different measures of contact tracing were computed in a large UK regional audit,
      and good correlation was found between the percentage of index cases with at
      least one contact seen and other measures of contact tracing. The importance of
      definition in the writing of standards to inform clinical practice is emphasized.

PMID- 16464279
TI  - A national audit of gonorrhoea management.
AB  - A national audit of gonorrhoea clinic policy and case management was carried out
      by postal survey on behalf of the National Audit Group of the British Association
      for Sexual Health and HIV. Ninety-three clinics out of a total of 278 (33%) and
      1324 cases were included. The results showed that both the auditable outcome
      measures listed in the National Guideline for the Management of Gonorrhoea in
      Adults and the evidence-based outcome standards recently published by Low et al.
      were broadly being met.

PMID- 16464278
TI  - Prevalence of Chlamydia trachomatis in sexual contacts of gonorrhoea.
AB  - The British national and local clinic guidelines recommend epidemiological
      treatment for Chlamydia trachomatis (CT) in patients with gonococcal infection
      but not their contacts. We aimed to determine the prevalence of CT amongst all
      gonorrhoea contacts attending over a 30 months period through a retrospective
      notes review. Of 223 contacts, gonorrhoea was diagnosed in 110 (49.3%) while CT
      was diagnosed in 54 (24.2%). CT was significantly more prevalent in younger
      people [(37.8% of contacts <25 years versus 9.6% of contacts >/=25 years (P =
      0.000)]. All patients with CT identified as heterosexual except one. Amongst
      heterosexuals, there was no significant difference in the prevalence between
      males and females, being 31.6% and 27.8% respectively (P = 0.5995). CT was
      prevalent in 29.1% of N. gonorrhoeae positive contacts and 19.5% of N.
      gonorrhoeae negative contacts (p = 0.0935). The high prevalence suggests that
      epidemiological treatment for CT in gonorrhoea contacts is indicated.

PMID- 16464280
TI  - Penile carcinoma arising in balanitis xerotica obliterans.
AB  - Squamous cell carcinoma of the penis is an uncommon cancer, though in one study
      it accounted for 90% of all penile cancers. Its association with balanitis
      xerotica obliterans (BXO) is a rare though recognized occurrence. We describe a
      case of a 46-year-old Caucasian male who first presented to our open-access
      clinic with a mild phimosis. An elective circumcision was performed and
      histological examination of the circumcision specimen showed BXO. He was lost to
      follow-up but re-presented three years later with a persistent tender penile
      ulcer which on biopsy showed no obvious sinister pathology. He returned a further
      two years later with a short history of bleeding from the ulcer, and another
      biopsy now confirmed penile squamous cell carcinoma. Our case emphasizes the
      importance of regular review of patients with BXO, in particular those with
      persistent symptoms.

PMID- 16464281
TI  - Neisseria gonorrhoeae: a rare cause of preseptal cellulitis?
AB  - We describe a case of preseptal cellulitis that presented initially to the
      ophthalmology department in our hospital. Neisseria gonorrhoeae, a very rare
      cause of this common condition, was isolated from a swab and the patient
      successfully treated with appropriate therapy. We review some aspects of non
      sexual transmission as the patient denied recent sexual contact and we were
      unable to isolate the organism from any other site.

PMID- 16464282
TI  - Pseudohepatic tumour associated with secondary syphilis in an HIV-positive male.
AB  - Inflammatory pseudohepatic tumours are unusual tumour-like conditions which can
      easily be mistaken for malignant lesions or liver abscesses. Patients usually
      present with fever, abdominal pain and loss of weight. The aetiology is unclear
      but the predominant inflammatory pattern of pathology and the associated systemic
      reactions suggest an underlying infectious agent. In the majority, microorganisms
      are not detected. As even routine imaging procedures usually fail to distinguish
      hepatic pseudotumours from liver neoplasms, biopsy is the definitive means of
      diagnosis. Until now, no case of pseudohepatic tumour has been reported as being
      associated with secondary syphilis. We believe secondary syphilis is the cause of
      this pseudohepatic tumour in our HIV-positive male.

PMID- 16464283
TI  - Screening for syphilis in HIV-positive men who have sex with men (MSM).

PMID- 16464284
TI  - Age of acquisition effects on an object-name verification task.
AB  - Naming latencies for words, objects and faces have been shown to be affected by
      the age at which an item is acquired (AoA). Originally, this effect was explained
      in terms of differential access to name representations. However, a number of
      recent studies have found AoA effects in tasks which do not require access to
      names (e.g. Brysbaert, Van Wijnendaele, & De Deynes, 2000; Lewis, 1999; Moore,
      Smith Spark, & Valentine, 2004; Moore & Valentine, 1999). Ellis and Lambon Ralph
      (2000) propose an alternative account of AoA, predicting that the effect should
      arise in any task where previously stored information is retrieved. The current
      study explored the effect of AoA on an object-name verification task. Experiments
      1 and 2 demonstrated that early acquired objects were verified significantly
      faster than later acquired objects. A third experiment collected naming latencies
      for the same picture stimuli in order to allow a comparison of the magnitude of
      the AoA effect for object verification and naming. The implications of these
      findings for accounts of AoA and its locus of effect are discussed.

PMID- 16464286
TI  - Do adult readers know how they read? Evidence from eye movement patterns and
      verbal reports.
AB  - The present study was carried out to investigate individual differences in
      reading styles among competent adult readers and to examine whether readers are
      aware of their reading style. Individual reading strategies were studied by
      having the participants read a long expository text while their eye fixation
      patterns were registered. A cluster analysis was performed on the eye movement
      data to distinguish between different reading styles. The analysis revealed three
      types of readers that were coined, following Hyona, Lorch, and Kaakinen (2002),
      fast linear readers, slow linear readers, and topic structure processors.
      Readers' procedural awareness of their reading behaviour was assessed by a
      questionnaire. The verbal reports obtained by the questionnaire were then
      correlated with the corresponding eye behaviour to investigate the extent to
      which the readers behave the way they report doing. The correlations showed that
      adult readers are well aware of their general reading speed and reasonably aware
      of their lookback and rereading behaviour. The amount of time spent looking back
      in text also correlated positively with the relative success in recalling the
      main points expressed in the text. It is concluded that systematic and extensive
      looking back in text is indicative of strategic behaviour.

PMID- 16464285
TI  - Face-specific configural processing of relational information.
AB  - Face processing relies on configural processing, which is thought to be
      particularly disrupted by inversion. We compared inversion effects in recognition
      experiments for three types of stimuli, using faces (Experiment 1) and houses
      (Experiment 2). Stimuli varied by their colour only (colour), by the spatial
      relations between components (relational), or by the components themselves (eyes,
      mouths, doors). For faces, relational versions revealed strong inversion effects,
      component versions moderate, and colour versions no inversion effect. Recognition
      of houses revealed no inversion effects at all. We suggest that the inversion
      effects observed for faces in the component condition are due to relational
      changes, which must accompany any change in components. This proposal may account
      for the rather inconsistent effects of inversion reported in the literature.
      Furthermore, we suggest configural processing seems to be somehow face-specific.

PMID- 16464287
TI  - Change blindness and visual memory: visual representations get rich and act poor.
AB  - Change blindness is often taken as evidence that visual representations are
      impoverished, while successful recognition of specific objects is taken as
      evidence that they are richly detailed. In the current experiments, participants
      performed cover tasks that required each object in a display to be attended.
      Change detection trials were unexpectedly introduced and surprise recognition
      tests were given for nonchanging displays. For both change detection and
      recognition, participants had to distinguish objects from the same basic-level
      category, making it likely that specific visual information had to be used for
      successful performance. Although recognition was above chance, incidental change
      detection usually remained at floor. These results help reconcile demonstrations
      of poor change detection with demonstrations of good memory because they suggest
      that the capability to store visual information in memory is not reflected by the
      visual system's tendency to utilize these representations for purposes of
      detecting unexpected changes.

PMID- 16464288
TI  - Haven't we met before? The effect of facial familiarity on repetition priming.
AB  - Within the word recognition literature, word-frequency and hence familiarity has
      been shown to affect the degree of repetition priming. The current paper reports
      two experiments which examine whether familiarity also affects the degree of
      repetition priming for faces. The results of Experiment 1 confirmed that
      familiarity did moderate the degree of priming in a face recognition task. Low
      familiarity faces were primed to a significantly greater degree than high
      familiarity faces in terms of accuracy, speed, and efficiency of processing.
      Experiment 2 replicated these results but additionally, demonstrated that
      familiarity moderates priming for name recognition as well as face recognition.
      These results can be accommodated within both a structural account of repetition
      priming (Burton, Bruce & Johnston, 1990) and an Episodic Memory account of
      repetition priming (see Roediger, 1990), and are discussed in terms of a common
      mechanism for priming, learning and the representation of familiarity.

PMID- 16464289
TI  - Obsessive-compulsive disorder across developmental trajectory: cognitive
      processing of threat in children, adolescents and adults.
AB  - BACKGROUND: While the cognitive theory of obsessive-compulsive disorder (OCD) is
      one of the most widely accepted accounts of the maintenance of the disorder in
      adults, no study to date has systematically evaluated the theory across children,
      adolescence and adults with OCD. METHOD: This paper investigated developmental
      differences in the cognitive processing of threat in a sample of children,
      adolescents and adults with OCD. Using an idiographic assessment approach, as
      well as self-report questionnaires, this study evaluated cognitive appraisals of
      responsibility, probability, severity, thought-action fusion (TAF), thought
      suppression, self-doubt and cognitive control. It was hypothesised that there
      would be age related differences in reported responsibility for harm, probability
      of harm, severity of harm, thought suppression, TAF, self-doubt and cognitive
      control. RESULTS: Results of this study demonstrated that children with OCD
      reported experiencing fewer intrusive thoughts, which were less distressing and
      less uncontrollable than those experienced by adolescents and adults with OCD.
      Furthermore, responsibility attitudes, probability biases and thought suppression
      strategies were higher in adolescents and adults with OCD. Cognitive processes of
      TAF, perceived severity of harm, self-doubt and cognitive control were found to
      be comparable across age groups. CONCLUSIONS: These results suggest that the
      current cognitive theory of OCD needs to address developmental differences in the
      cognitive processing of threat. Furthermore, for a developmentally sensitive
      theory of OCD, further investigation is warranted into other possible age related
      maintenance factors. Implications of this investigation and directions for future
      research are discussed.

PMID- 16464290
TI  - Training for vigilance: the effect of knowledge of results format and
      dispositional optimism and pessimism on performance and stress.
AB  - This study investigated the impact of knowledge of results (KR) format on the
      performance and stress associated with a vigilance task. Also examined was the
      effect of the interaction of KR-format (Hit-KR, False Alarm-KR, Miss-KR, and a
      composite of all three formats) with dispositional optimism and pessimism on
      performance outcome and reported stress state. Hypotheses based upon a theory of
      feedback intervention were tested. KR regarding correct detections and the
      composite-KR (KR regarding correct detections, false alarms, and missed signals)
      enhanced perceptual sensitivity. However, False Alarm-KR and Miss-KR did not.
      Contrary to expectations based on the theory, performance was unrelated to the
      traits across all KR conditions. However, the effects of KR-format on self
      reports of stress depended on the individual's level of pessimism and optimism.
      In addition, KR format and personality affected the multiple dimensions of stress
      state in different ways.

PMID- 16464311
TI  - Impact of umbelliferone on erythrocyte redox status in STZ-diabetic rats.
AB  - Oxidative stress is currently hypothesized to be a mechanism underlying diabetes.
      The present study was designed to evaluate the effect of umbelliferone (UMB), a
      derivative of coumarin, on erythrocyte lipid peroxidation, antioxidants, and
      lipid profile in normal and streptozotocin (STZ) diabetic rats. Diabetes was
      induced in adult male albino rats of Wistar strain, weighing 180 to 200 g, by the
      administration of STZ (40 mg/kg/b-wt) intraperitonially. The normal and diabetic
      rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) dissolved in
      water for 45 days. The diabetic rats had elevated levels of blood glucose and
      lipid peroxidation markers such as thiobarbituric acid reactive substances
      (TBARS), conjugated dienes (CD), and lipid hydroperoxide (HP) and decreased
      levels of nonenzymatic antioxidants (Vitamin C and reduced glutathione [GSH]),
      elevated levels of vitamin E, and elevated levels of enzymatic antioxidants
      (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]),
      elevated glucose-6-phosphate dehydrogenase activity, and altered lipid profile
      (cholesterol and phospholipids) in erythrocytes. These changes were reversed by
      treatment with UMB. Thus, our results indicate that the administration of UMB
      shows promising potential for the restoration of normal blood glucose levels,
      erythrocyte lipid peroxidation, antioxidants, and lipid profile in STZ-diabetic.

PMID- 16464312
TI  - Fibrous dysplasia of the cranial bones: a case report and review of the
      literature.
AB  - Fibrous dysplasia (FD) is a relatively uncommon disorder that affects primarily
      the cranial region; its occurrence in the cranial base in combination with
      hindbrain herniation and aneurysmal bone cyst (ABC) constitutes an extremely rare
      condition. We report a case of polyostotic fibrous dysplasia with progressive
      occipital, temporal, and clival involvement. Clinical findings and differential
      diagnosis with special emphasis on the imaging features were discussed. A small
      posterior fossa volume has been thought to lead to hind brain herniation. The
      resultant obstruction to the CSF pathways at the level of the foramen magnum has
      been implicated in the development and subsequent progression of syringobulbia.

PMID- 16464314
TI  - Carotid artery injury with cerebral infarction following head and neck blunt
      trauma: report of a case.
AB  - Blunt injury to the carotid artery is rare but may produce a devastating outcome
      with longterm morbidity. Initial recognition by clinicians is often difficult
      because of the diverse clinical manifestations, the delay in presentation of
      symptoms, and the associated multi-organ system injuries that accompany carotid
      injury. Early diagnosis and successful management of traumatic carotid artery
      injury require a high index of clinical suspicion. We report herein a 20-year-old
      male victim of internal carotid artery injury induced by a motorcycle accident,
      who initially presented with a clear consciousness and had normal computed
      tomogram (CT) of brain. Two days after injury, the patient suffered from left
      hemiplegia and coma. The follow-up brain CT showed acute infarction of right
      cerebrum and severe cerebral edema. Emergency craniotomy for brain decompression
      and anticoagulation therapy was carried out. After a three-month treatment, he
      was discharged and underwent regular follow-up in the outpatient department. Six
      months later, the patient had intact awareness but remained in a left-sided
      hemiparetic state.

PMID- 16464313
TI  - Myocardial infarction after taking zolmitriptan.
AB  - We report the case of a patient with mild non-obstructive coronary artery disease
      who sustained an inferior wall myocardial infarction shortly after taking
      zolmitriptan as abortive therapy for migraine headaches. A Medline search was
      performed to review all reported cases of myocardial infarction related to
      migraine therapy with zolmitriptan and related medications. Zolmitriptan may
      cause myocardial infarction (MI) even in the absence of significant coronary
      artery disease.

PMID- 16464315
TI  - Diagnosing pulmonary emboli: a critical review for the clinician and radiologist.

PMID- 16464316
TI  - The early history of kidney transplantation at Yale (1967-1985): a personal
      memoir.

PMID- 16464318
TI  - GPs can no longer claim to be the "gatekeepers" of the NHS.

PMID- 16464319
TI  - Care of patients with intellectual or learning disability in primary care: no
      more funding so will there be any change?

PMID- 16464320
TI  - GP job satisfaction in view of contract reform: a national survey.
AB  - BACKGROUND: Job satisfaction has been associated with intentions to quit and
      aspects of quality of care. In 2001, GP job satisfaction in England had fallen to
      its lowest point for over a decade. AIM: To assess GP job satisfaction and
      stressors immediately prior to implementation of the 2004 contract. DESIGN OF
      STUDY: National survey of a random sample of GPs. SETTING: England. METHOD: One
      thousand, nine hundred and fifty principal and salaried GPs surveyed in February
      2004 were compared with 1828 principals surveyed in 1998 and 1841 principal and
      salaried GPs surveyed in 2001. Job satisfaction and stressor scores were adjusted
      for 2004 age-sex distributions. Determinants of overall satisfaction were
      examined through ordinary least squares regression. RESULTS: The 2004 response
      rate was 53%. GPs were most dissatisfied with hours of work, recognition for good
      work and remuneration, and experienced most pressure from paperwork, increasing
      workloads and having insufficient time. The majority of doctors were satisfied
      with their job overall. Satisfaction was higher than in 2001 and approximately
      the same as in 1998. Overall stress in 2004 was lower than in 2001 but still
      higher than in 1998. After allowing for personal, practice and job
      characteristics, higher satisfaction was associated with lower job stress,
      involvement in decision making, increasing job interest and ability to meet
      conflicting demands. CONCLUSIONS: Despite recent initiatives to enhance workforce
      capacity and working lives for GPs, workload, time pressures and job control
      remain potential areas of concern. Addressing such issues may be key to
      maintaining morale as the new contract is implemented.

PMID- 16464321
TI  - Previously unidentified morbidity in patients with intellectual disability.
AB  - BACKGROUND: Adults with a learning disability frequently have unmet health needs.
      The cause for this is complex and may be related to difficulties in accessing
      usual primary care services. Health checks have been widely recommended as a
      solution to this need. AIM: To determine the likelihood that a structured health
      check by the primary care team supported by appropriate education would identify
      and treat previously unrecognised morbidity in adults with an intellectual
      disability. DESIGN OF STUDY: Individuals were identified within primary care
      teams and a structured health check performed by the primary care team. This
      process was supported by an educational resource. Face-to-face audit with the
      team was performed 3 months following the check. SETTING: Forty general practices
      within three health authorities in south and mid-Wales participated. They had a
      combined registered patient population of 354 000. METHOD: Health checks were
      conducted for 190 (60%) of 318 identified individuals; 128 people moved, died,
      withdrew from the study, or refused to participate. RESULTS: Complete data were
      available on 181 health checks; 51% had new needs recognised, of whom 63% had one
      health need, 25% two health needs, and 12% more than two. Sixteen patients (9%)
      had serious new morbidity discovered. Management had been initiated for 93% of
      the identified health needs by the time of audit. This study is the first to
      identify new disease findings in a primary care population and the likelihood
      that such disease will be treated. CONCLUSIONS: The findings reflect a concern
      that current care delivery leaves adults with an intellectual disability at risk
      of both severe and milder illness going unrecognised. Health checks present one
      mechanism for identifying and treating such illness in primary care.

PMID- 16464322
TI  - Opportunistic and systematic screening for chlamydia: a study of consultations by
      young adults in general practice.
AB  - BACKGROUND: Opportunistic screening for genital chlamydia infection is being
      introduced in England, but evidence for the effectiveness of this approach is
      lacking. There are insufficient data about young peoples' use of primary care
      services to determine the potential coverage of opportunistic screening in
      comparison with a systematic population-based approach. AIM: To estimate use of
      primary care services by young men and women; to compare potential coverage of
      opportunistic chlamydia screening with a systematic postal approach. DESIGN OF
      STUDY: Population based cross-sectional study. SETTING: Twenty-seven general
      practices around Bristol and Birmingham. METHOD: A random sample of patients aged
      16-24 years were posted a chlamydia screening pack. We collected details of face
      to-face consultations from general practice records. Survival and person-time
      methods were used to estimate the cumulative probability of attending general
      practice in 1 year and the coverage achieved by opportunistic and systematic
      postal chlamydia screening. RESULTS: Of 12 973 eligible patients, an estimated
      60.4% (95% confidence interval [CI] = 58.3 to 62.5%) of men and 75.3% (73.7 to
      76.9%) of women aged 16-24 years attended their practice at least once in a 1
      year period. During this period, an estimated 21.3% of patients would not attend
      their general practice but would be reached by postal screening, 9.2% would not
      receive a postal invitation but would attend their practice, and 11.8% would be
      missed by both methods. CONCLUSIONS: Opportunistic and population-based
      approaches to chlamydia screening would both fail to contact a substantial
      minority of the target group, if used alone. A pragmatic approach combining both
      strategies might achieve higher coverage.

PMID- 16464323
TI  - Prevalence of STI related consultations in general practice: results from the
      second Dutch National Survey of General Practice.
AB  - BACKGROUND: The role of the GP in the care of sexually transmitted infections
      (STIs) is unclear. AIM: We studied the prevalence of STI related consultations in
      Dutch general practice in order to obtain insight into the contribution of the GP
      in STI control. DESIGN OF STUDY: A descriptive study. SETTING: The study took
      place within the framework of the second Dutch National Survey of General
      Practice in 2001, a large nationally representative population-based survey.
      METHOD: During 1 year, data of all patient contacts with the participating GPs
      were recorded in electronic medical records. Contacts for the same health problem
      were clustered into disease episodes and their diagnosis coded according to the
      International Classification of Primary Care. All STI and STI related episodes
      were analysed. RESULTS: In total, 1 524 470 contacts of 375 899 registered
      persons in 104 practices were registered during 1 year and 2460 STI related
      episodes were found. The prevalence rate of STI was 39 per 10 000 persons and of
      STI/HIV related questions 23 per 10 000. More than half of all STIs were found in
      highly urbanised areas and STIs were overrepresented in deprived areas. Three
      quarters of all STIs diagnosed in the Netherlands are made in general practice.
      An important number of other reproductive health visits in general practice offer
      opportunities for meaningful STI counselling and tailored prevention. DISCUSSION:
      GPs contribute significantly to STI control, see the majority of patients with
      STI related symptoms and questions and are an important player in STI care. In
      particular, GPs in urban areas and inner-city practices should be targeted for
      accelerated sexual health programmes.

PMID- 16464324
TI  - Persistent increase in the incidence of acute male urethritis diagnosed in
      general practices in France.
AB  - BACKGROUND: At-risk sexual behaviour seems to have increased in Europe, possibly
      due to the reassuring efficacy of highly active antiretroviral treatments. AIM:
      To follow, from 1990 to 2003, in France, the trends in the incidence of acute
      male urethritis diagnosed in general practice, a marker of at-risk sexual
      behaviour. DESIGN OF STUDY: Electronic disease surveillance. SETTING: General
      practices located all over mainland France. METHOD: The GPs of the French
      Sentinelles network reported, via online computer systems, the acute urethritis
      cases they diagnosed, and for each case the characteristics of the patients.
      RESULTS: After a striking decrease between 1990 and 1995 from 460 per 100 000 men
      aged 15-64 years (95% confidence interval [CI] = 390 to 520) to 180 (95% CI = 150
      to 200), when antiretroviral drugs became available on the French market, the
      incidence of acute male urethritis stopped decreasing. Between 1996 and 2003, it
      may have risen again from 190 per 100 000 men (95% CI = 160 to 210) to 325 per
      100 000 men (95% CI = 280 to 370) aged 15-64 years. The percentage of
      homosexual/bisexual men among the cases reported was higher than in the general
      population (10% versus 4%, P<0.001). Homosexual/bisexual patients were younger
      than heterosexual patients (34 versus 37 years, P = 0.04), more of them had a
      discharge (88% versus 59%, P<0.001), a history of sexually transmitted disease
      (65% versus 32%, P<0.001), and at least two sexual partners (74% versus 38%,
      P<0.001). The most frequent pathogens were Chlamydia trachomatis (25%), Neisseria
      gonorrhoea (21%), Mycoplasma genitalium (8%), Ureaplasma urealyticum (5%),
      Trichomonas vaginalis (3%) and other bacteria (32%). Presence of co-infections
      was observed in 8.3% of patients. CONCLUSIONS: This increase in the incidence of
      urethritis, shows that the sexual health of men has worsened in France, and calls
      for urgent new preventive measures.

PMID- 16464325
TI  - Gut-directed hypnotherapy for irritable bowel syndrome: piloting a primary care
      based randomised controlled trial.
AB  - BACKGROUND: In western populations irritable bowel syndrome (IBS) affects between
      10% and 30% of the population and has a significant effect on quality of life. It
      generates a substantial workload in both primary and secondary care and has
      significant cost implications. Gut-directed hypnotherapy has been demonstrated to
      alleviate symptoms and improve quality of life but has not been assessed outside
      of secondary and tertiary referral centres. AIM: To assess the effectiveness of
      gut-directed hypnotherapy as a complementary therapy in the management of IBS.
      DESIGN OF STUDY: Randomised controlled trial. SETTING: Primary care patients aged
      18-65 years inclusive, with a diagnosis of IBS of greater than 6 weeks' duration
      and having failed conventional management, located in South Staffordshire and
      North Birmingham, UK. METHOD: Intervention patients received five sessions of
      hypnotherapy in addition to their usual management. Control patients received
      usual management alone. Data regarding symptoms and quality of life were
      collected at baseline and again 3, 6, and 12 months post-randomisation. RESULTS:
      Both groups demonstrated a significant improvement in all symptom dimensions and
      quality of life over 12 months. At 3 months the intervention group had
      significantly greater improvements in pain, diarrhoea and overall symptom scores
      (P<0.05). No significant differences between groups in quality of life were
      identified. No differences were maintained over time. Intervention patients,
      however, were significantly less likely to require medication, and the majority
      described an improvement in their condition. CONCLUSIONS: Gut-directed
      hypnotherapy benefits patients via symptom reduction and reduced medication
      usage, although the lack of significant difference between groups beyond 3 months
      prohibits its general introduction without additional evidence. A large trial
      incorporating robust economic analysis is, therefore, urgently recommended.

PMID- 16464326
TI  - Symptom interpretation and quality of life in patients with irritable bowel
      syndrome.
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) are often believed to
      attribute unexplained symptoms to physical disorders. We tested this hypothesis
      by assessing symptom interpretation, symptom severity, and quality of life in
      patients attending hospital gastroenterology clinics. AIM: The main aims of this
      study were: to assess the symptom attributional styles of hospital
      gastroenterological outpatients with IBS and non-IBS disorders in comparison with
      unselected patients attending their GP; to establish the relationships between
      attributional style, quality of life, and IBS severity score in hospital
      gastroenterology outpatients; and to test the hypothesis that the IBS severity
      score correlates with a somatising style of symptom attribution. DESIGN OF STUDY:
      Systematic quantitative analysis. SETTING: General practice and gastroenterology
      outpatient clincs. METHOD: Patients attending hospital gastroenterology clinics
      were recruited prospectively and completed validated questionnaires. These were
      the Medical Outcome Survey (MOS SF-36), the IBS Severity Score, and the Symptom
      Interpretation Questionnaire (SIQ). The latter measures the tendency to interpret
      somatic symptoms in three ways: as a physical disorder (somatising attributional
      style), as an emotional response to stress (psychologising attributional style),
      or as a normal experience (normalising attributional style). The diagnosis of IBS
      was based on the Rome II criteria; the control groups comprised gastroenterology
      outpatients with non-IBS diagnoses and unselected patients attending general
      practice. RESULTS: Quality of life in IBS patients attending hospital outpatients
      (n = 32, male:female ratio 9:23) was not significantly different from that of non
      IBS patients (n = 70, male:female ratio 32:38). In all patient groups, the
      normalising style of symptom interpretation predominated; psychologising styles
      correlated with impaired quality of life in the mental health domains. In IBS
      patients, the tendency to seek a psychological explanation for physical symptoms
      correlated significantly with the severity of the abdominal pain. CONCLUSIONS:
      Symptom interpretation does not differ between IBS and non-IBS patients referred
      to hospital gastroenterology clinics. The tendency to attribute somatic symptoms
      to a physical disorder does not explain why only a minority of IBS subjects seek
      medical attention. The idea that most IBS patients are committed to a somatic
      explanation of symptoms appears to be a myth.

PMID- 16464327
TI  - Comparison of two recruitment strategies for patients with chronic shoulder
      complaints.
AB  - BACKGROUND: Recruiting adequate numbers of participants represents a major
      problem to the completion of randomised clinical trials in primary care.
      Information on different recruitment strategies applied in one trial is scarce.
      AIM: To evaluate the application of two recruitment strategies in one trial.
      DESIGN OF STUDY: The study was performed within the framework of a randomised
      clinical trial on the effectiveness of a behavioural treatment for patients with
      chronic shoulder complaints. SETTING: Thirty-two general practices in the
      Netherlands. METHOD: Patients recruited during a consultation with their GP for
      chronic shoulder complaints were compared with patients recruited by
      advertisement in a local newspaper as regards baseline characteristics,
      withdrawals (drop-outs and losses to follow-up) and post-treatment clinical
      outcomes. RESULTS: Patients recruited by the GPs (n = 83) were similar to those
      recruited by advertisement (n = 83) in terms of demographic characteristics and
      clinical outcome measures at baseline, but differed slightly in disease
      characteristics and treatment preferences. Recruitment strategy was not related
      to reasons for or numbers of withdrawals. Improvements on outcome measures were
      greater in patients recruited by the GPs, irrespective of allocated treatment.
      Results on the clinical effectiveness of treatments at the end of the treatment
      period or during follow-up were neither modified by recruitment strategy, nor by
      differences between the two strategy groups in patient characteristics found at
      baseline. CONCLUSION: Using two recruitment strategies did not influence the
      outcomes on clinical effectiveness in this trial.However, recruitment strategy
      should be considered as a putative modifying factor in the design of a study.

PMID- 16464328
TI  - Workforce trends in general practice in the UK: results from a longitudinal study
      of doctors' careers.
AB  - The career paths of 544 UK medical school graduates were followed for 10 years.
      Although general practice was not attractive to graduates initially, it became
      popular in subsequent years, mainly because it was seen as offering a superior
      quality of life. Once in general practice both men and women chose to work
      reduced hours and/or in non-principal posts. The findings suggest the need to
      look more closely at the nature of these trends and the implications for patient
      care and service provision.

PMID- 16464329
TI  - Comparing GP and nurse practitioner consultations.

PMID- 16464330
TI  - Genuine asylum?

PMID- 16464331
TI  - Deprived people less likely to get treatment to prevent heart disease.

PMID- 16464332
TI  - Research governance: major barrier to medical student research.

PMID- 16464333
TI  - Limited resources?

PMID- 16464335
TI  - Nurse and pharmacist prescribing.

PMID- 16464338
TI  - Imaging in sinusitis.

PMID- 16464339
TI  - Telephone reviews of chronic illnesses.

PMID- 16464342
TI  - Non-bacterial acute conjunctivitis.

PMID- 16464343
TI  - GP education ... feeding hearts and minds.

PMID- 16464348
TI  - Straw man.

PMID- 16464349
TI  - A carer's lament.

PMID- 16464355
TI  - Cerebrovascular injury in stroke.

PMID- 16464356
TI  - Stroke research in China.
AB  - China reports more patients with stroke than anywhere else in the world. While
      there is still a great deal of unknown information, stroke research has been
      making great progress in recent years. This study will review and discuss a
      variety of factors such as clinical research, population and genetic
      epidemiology, brain ischemia/reperfusion exploring, leukoencephalopathy
      (CADASIL), neural stem cell and stroke, neuroprotective treatment for stroke,
      clinical therapy test in stroke, rehabilitation and prevention. Cities and towns
      in China have good integrated systems for registering and investigating strokes.
      Chinese researchers have followed closely the international level of stroke
      treatment with a forward position in neural stem cell. Traditional Chinese drugs
      have featured effects on neuroprotective treatment for stroke which has also been
      investigated. Chinese scientists suggested a new way of dividing neuroprotectors
      in stroke. The clinical therapy test with urokinase and defibrase for cerebral
      infarction in China is effective and relatively safe, yet the original papers
      published by Chinese researchers and clinical effects for patient treatment still
      need to be improved and updated.

PMID- 16464357
TI  - A survey on adherence to secondary ischemic stroke prevention.
AB  - Reduced adherence and compliance to discharge instructions and protocols could
      significantly influence the ability of any stroke prevention strategy. The goals
      of this investigation were to evaluate the adherence to secondary prevention
      strategies within 1 year after ischemic stroke and to identify possible causes of
      poor compliance with these strategies. Patients who had suffered either acute
      ischemic stroke or transient ischemic attacks (TIA) were recruited
      retrospectively through telephone follow-up. The survey included whether the
      patient was prescribed antithrombotic treatment at discharge and reasons for non
      compliance with this prescription both immediately after discharge and 1 year
      after discharge. Of 472 (73.8%) patients with detailed clinical data who were
      finally evaluated in this survey, 326 (69.1%) were still under antithrombotic
      treatment and 172 (36.4%) underwent the same antithrombotic agent as prescribed
      when discharged. We found that medical insurance and free medical care were able
      to promote compliance with medication in stroke patients for secondary
      prevention, while administration of non-aspirin antithrombotic agents or a poor
      ability for daily activities (Barthel index, BI) had significantly negative
      effects on medication compliance in stroke patients. Under the conditions of this
      observational study, adherence to stroke prevention strategies was poor. Income
      levels, categories of antithrombotic agents and the personal living ability are
      closely related to compliance. The results suggest that doctors should pay more
      attention to the secondary prevention of stroke. We suggest that providing stroke
      patients with detailed instructions for medication usage, physicians could
      increase the potential that their secondary prevention of stroke could be
      increased.

PMID- 16464358
TI  - Effects of ischemic preconditioning on blood-brain barrier permeability and MMP-9
      expression of ischemic brain.
AB  - The study was designed to investigate the effects of ischemic preconditioning
      (IP) on permeability of blood-brain barrier (BBB) and expression of matrix
      metalloproteinase-9 (MMP-9) in subsequent ischemic hemisphere. Rats were divided
      into four groups, one group was used as control, and the other three groups were
      given three different pretreatments: the first group received a saline injection
      into the right internal carotid artery (SI), the second group underwent both left
      and right carotid arteries occlusion (BCAO), and the third group was treated with
      BCAO and SI simultaneously (BS). After 24 hours of pretreatments, the focal
      cerebral ischemia was induced by inserting a thread into the right middle
      cerebral artery causing occlusion (MCAO). Brain water content, BBB permeability
      and MMP-9 expression of ischemic hemisphere brains were measured at 24 and 48
      hours after MCAO. After 24 and 48 hours MCAO, averages for brain water content
      were 82.92 and 83.12% in BS group, 85.19 and 85.73% in SI group and 86.06 and
      85.88% in BCAO group. Evans blue content of ischemic hemispheres were 14.01 and
      11.74 microg/mm(3) at 24 and 48 hours after MCAO in BS group, which were lower
      than the other two groups, 16.22, 15.01 and 16.61, 15.58 microg/mm(3),
      respectively (p<0.01). The expression levels of MMP-9 in ischemic hemisphere in
      BS were lower than that in other two groups (p<0.01). Therefore, ischemic
      preconditioning could ameliorate brain edema and BBB disruption caused by
      subsequent cerebral ischemia. Ischemic preconditioning could decrease MMP-9
      protein and mRNA expression, which may be an important mechanism of cerebral
      ischemic tolerance.

PMID- 16464359
TI  - Serum level of homocysteine is correlated to carotid artery atherosclerosis in
      Chinese with ischemic stroke.
AB  - OBJECTIVES: To investigate the relationship between serum level of homocysteine
      (Hcy) and carotid artery atheroscleosis (CAA). METHODS: Both sides of the common
      carotid artery and internal carotid artery in 126 Chinese patients with ischemic
      stroke were measured by B-mode ultrasound. The patients were divided into groups:
      normal, A, B, C and D according to the severity of CAAs. With fasting serum, Hcy
      as well as folate, vitamin B(12) and lipids were detected. The mean +/- SD age
      was 64 +/- 13 years (range 39-87 years). RESULTS: In a logistic regression model,
      the Hcy concentrations were associated with an elevated risk of CAAs independent
      of all traditional risk factors, and when CAAs became severer, the serum Hcy was
      higher. The levels of the normal group and A, B, C, D groups were 13.22 +/- 6.15
      micromol/L, 16.29 +/- 9.81 micromol/l, 19.49 +/- 11.16 micromol/l, 27.21 +/-
      17.47 micromol/l, and 24.14 +/- 8.64 micromol/l, respectively. Rank test showed a
      significant difference between normal and other groups (p<0.05). The levels of
      folate and vitamin B(12) were negatively correlated with the Hcy concentrations.
      Spearman correlation coefficient were -0.23 and -0.42 (p<0.05). CONCLUSIONS:
      Hyperhomocysteinaemia is an independent risk factor of CAAs and the degree of
      CAAs is highly correlated with the level of Hcy in serum. The causes of
      hyperhomocysteinemia may be the result from the decrease in folate and vitamin
      B(12). Clinical trials are now required to evaluate the effect of treatment with
      these vitamins on the primary and secondary prevention of cerebral vascular
      diseases.

PMID- 16464360
TI  - A new method of noninvasive brain-edema monitoring in stroke: cerebral electrical
      impedance measurement.
AB  - OBJECTIVE: To explore the primary regularity of cerebral electrical impedance
      (CEI) change in healthy people, patients with intracerebral hemorrhage (ICH) and
      patients with cerebral infarction (CI). METHODS: CEI of 200 healthy volunteers,
      78 patients with ICH and 51 patients with CI were measured by noninvasive brain
      edema monitor. The results of perturbative index (PI) converted from CEI were
      compared with the volumes of infarction, hematoma and surrounding edema, which
      were calculated by image analysing system according to MRI or CT scan. RESULTS:
      (1) In the normal groups, PI in the left and right sides of cerebral hemispheres
      was respectively 7.98 +/- 0.95 and 8.02 +/- 0.71, and there was no significant
      difference between the two sides (p>0.05). (2) In the patients with ICH, PI of
      the hematoma side initially was lower than the other side, but then increased and
      finally exceeded that of the other side. The average transitional time was 19.67
      +/- 11.52 hours. Perturbative index of the hematoma side after the transitional
      time was much higher than before the transitional time in the same patients (7.79
      +/- 0.75 versus 7.09 +/- 0.72) (p<0.001). The volumes of peri-hematoma edema were
      also significantly larger after the transitional time than before (24.32 +/-
      12.86 versus 13.33 +/- 6.12) (p<0.05). There was a positive correlation between
      the PI of hematoma side and the volumes of peri-hematoma edema (p<0.01). (3) In
      the patients with arterothrombotic cerebral infarction, PI in the infarct side
      was higher than that in the opposite side 3-5 days after onset (8.93 +/- 1.89
      versus 8.58 +/- 1.61) (p<0.001), and PI of the infarct side had a positive
      correlation with the volume of infarction (p<0.001). (4) The sensitivity of PI
      was high when the volumes of lesions were >20 ml or the position of them were
      located in the basal ganglia, but was low when the volumes were <20 ml or the
      position near the midline. CONCLUSION: CEI may be a useful parameter for
      noninvasively monitoring the change of brain edema and hematoma in stroke at
      bedside. It could be a good complement to CT and MRI.

PMID- 16464361
TI  - Expression of heme oxygenase-1 protein and messenger RNA in permanent cerebral
      ischemia in rats.
AB  - BACKGROUND: Carbon monoxide has been regarded as a gaseous molecular messenger
      like nitric oxide. PURPOSE: To clarify the role of heme oxygenase-1 in the
      permanent cerebral ischemia at the protein and mRNA level. METHODS: The
      expression of heme oxygenase-1 protein and messenger RNA was investigated at
      different time points following MCAO using immunohistochemistry, Western
      blotting, RT-PCR, and Northern blotting. RESULTS: Increased HO 1immunoreactivity
      was detected in hippocampal and cortical neurons after 1 hour of ischemia, and
      was also observed in astroglial cells. After 12 hours of ischemia, HO-1 was found
      in both neurons and glia in cerebral cortex and thalamus, and in striatal glia
      cells. Western blotting analysis show the expression of HO-1 protein in cortical
      neurons reached the peak after 12 hours of occlusion and decreased gradually, but
      was still detected at day 7 post-occlusion. The expression of messenger RNA was
      examined in the brains of rats subjected to permanent cerebral ischemia by semi
      quantitative RT-PCR and Northern blotting. HO-1 mRNA transcription could be
      detected 1 hour after occlusion. After 1 to 6 hours of occlusion, the expression
      of HO-1 rose rapidly, reaching a peak at 12 hours post-occlusion, decreased
      gradually, and lasted until day 7 of occlusion. Although HO activity of cerebral
      tissue can be detected in both sham-operated group and operated groups, the HO
      activity in operated groups is much stronger than that in sham-operated group.
      CONCLUSIONS: The induction of HO-1 protein may protect cerebral tissues from
      ischemic damage.

PMID- 16464363
TI  - A study on blood-brain barrier ultrastructural changes induced by cerebral
      hypoperfusion of different stages.
AB  - OBJECTIVES: To evaluate the ultrastructural changes in the blood-brain barrier
      (BBB) induced by cerebral hypoperfusion of different stages, which may predispose
      the brain to the formation of vasogenic edema and hemorrhage under cerebral
      luxury perfusion. METHODS: Twenty cerebral steal models with left neck
      arteriovenous fistula (AVF) were surgically created in Wistar's rats, leading to
      a noninfarctional reduction in the cerebral blood flow (CBF) by between 25 and
      50%, resulting in cerebral hypoperfusion in the AVF side for 3 days (acute
      stage), 3 weeks (subacute stage) and 3 months (chronic stage), respectively.
      Another six sham-operated models were made in age-matched rats as control. The
      BBB ultrastructural changes were assessed by transmission electron microscopy.
      Ridit analysis was conducted to compare the positive ratio of ultrastructural
      changes among multiple groups. RESULTS: Electron microscopy demonstrated no
      ultrastructural change at the acute stage, however, at the subacute stage, slight
      vacuolar degeneration was found in the astrocytic foot process layer encircling
      the capillaries; furthermore, at the chronic stage, the astrocytic foot processes
      expressed marked vacuolization associated with the adjacent astrocytic
      degeneration. Meanwhile, in both capillary endothelium and basal lamina layers,
      no abnormal ultrastructures similar to those in the astrocytic foot processes
      layer were identified. After cerebral luxury perfusion took place, BBB was
      disrupted where astrocytic foot processes vacuolization was most distinguished.
      CONCLUSION: Astrocytes generate ultrastructural abnormality as a result of
      chronic cerebral hypoperfusion. Astrocytic foot process vacuolization, which
      constitutes the major ultrastructural change in the BBB, is the extension of the
      degeneration of astrocyte body. It is inferred that BBB is prone to structure
      weakness and function instability, which forms the morphological basis of
      cerebral luxury perfusion.

PMID- 16464362
TI  - Dynamic change of coagulation and anticoagulation markers of patients with acute
      cerebral infarction during intravenous urokinase thrombolysis.
AB  - BACKGROUND AND OBJECTIVE: The variations of blood coagulation and anticoagulation
      are of clinical importance in patients with acute cerebral infarction during
      intravenous urokinase (UK) thrombolysis. Although intravenous heparin is commonly
      used after thrombolytic therapy, few reports have addressed the relationship
      between the degree of anticoagulation and clinical outcomes, specifically the
      effect of thrombolytic agents on hemostasis. In this study, we dynamically
      monitored the activated partial thromboplastin time (APTT), the prothrombin time
      (PT), the thrombin time (TT) and the activated partial thromboplasmin time (APTT)
      in 56 patients with acute cerebral infarction during intravenous urokinase
      thrombolysis and analysed the relationship among the blood coagulation biomarkers
      (APTT, PT, TT, AT-III), as well as baseline patient characteristics and clinical
      outcomes. This allowed us to explore the valuable biomarkers for securing the
      thrombolysis regimen in clinical practice. METHODS: The levels of PT, APTT, TT
      and AT-III in peripheral blood of 56 patients with acute cerebral infarction and
      50 normal controls were assayed by ELISA. Dynamic transformation of these markers
      at the baseline and the time points of the first, second, fourth, eighth, 12th,
      24th, 48th, 72nd and 96th hour after intravenous UK thrombolysis was monitored
      serially. The relationship between the levels of these biomarkers and the
      clinical effectiveness and safety of urokinase thrombolysis was evaluated.
      RESULTS: The levels of PT, APTT, TT and AT-III in patients before intravenous UK
      thrombolysis were significantly lower than those in age- and sex-matched normal
      controls (all p<0.05). After treatment with UK, the levels of PT and APTT rose
      quickly during the first 4 hours (all p< 0.05), and then gradually recovered,
      reaching baseline at about the 48th hour. The activity of AT-III was slightly
      increased and showed fluctuations after UK infusion (p< 0.05), however the
      fluctuated range was not remarkable and lacked specificity. CONCLUSIONS: Dynamic
      monitoring of PT, APTT and TT can indicate coagulative and anticoagulative
      functions of patients with acute cerebral infarction during intravenous urokinase
      thrombolysis. Monitoring of these markers can be helpful both in regulating the
      infusion speed and the dosage of UK, as well as increasing the efficacy and
      safety of UK therapy. However, assay for AT-III might be unnecessary.

PMID- 16464364
TI  - Study on the pathogenic mechanism of Broca's and Wernicke's aphasia.
AB  - OBJECTIVE: To study the mechanisms of aphasia by observing cerebral blood flow
      and metabolism changes in language functional areas of the brain using imaging,
      in order to develop a language rehabilitation plan for aphasia patients. METHODS:
      Fifty-eight patients who suffered from Broca's or Wernicke's aphasia secondly to
      cerebral infarction were evaluated using the Western aphasia battery and Frenchay
      dysarthria assessment. CT and MRI were obtained to identify the location of
      lesions, and the language areas were analysed with magnetic resonance
      spectroscopy (MRS) and perfusion-weighted imaging (PWI). The results were
      compared with those of the contralateral hemisphere. RESULTS: Of the 58 patients,
      there were 23 Broca's aphasia patients, 29 Wernicke's aphasia patients and six
      other aphasia types. We excluded five patients accompanied by dysarthria, six
      patients with other aphasia types and 14 patients with much more disease lesions.
      Finally, we analysed the remaining 12 Broca's aphasia and 21 Wernicke's aphasia
      patients by MRS and PWI. MRS shows that the N-acetylaspartate, choline and
      creatine of the Broca's or Wernicke's area were reduced than those of the
      contralateral hemisphere, while PWI results show that the damaged Broca's or
      Wernicke's areas were in a hypoperfusion state. CONCLUSIONS: Broca's or
      Wernicke's area of aphasia patients exhibits hypoperfusion and hypometabolism,
      indicating that they might be the mechanisms of Broca's or Wernicke's aphasia.

PMID- 16464365
TI  - Quantitative evaluation for secondary injury to perihematoma of hypertensive
      cerebral hemorrhage by functional MR and correlation analysis with ischemic
      factors.
AB  - OBJECTIVES: To analyse quantitatively for the secondary injury to the
      perihematoma region of intracerebral hemorrhage (ICH) patients by functional MR
      imaging technique. METHODS: 35 ICH patients were recruited and performed T1, T2,
      perfusion weight imaging (PWI), diffusion weight imaging (DWI) and FLAIR sequence
      scanning. Hematoma volume and edema volume of perihematomal area as well as
      parameters of blood volume [regional cerebral blood volume (rCBV), mean transit
      time (MTT)] alteration were calculated. RESULTS: Varied blood flow decline was
      detected in the patients on the perihematoma sides, compared with the
      corresponding area of the opposite sides. There was significant difference of
      rCBV and MTT (p=0.00) and mild negative correlation between rCBV and hematoma
      volume (p=0.00) among groups; edema volume of perihematoma region and hematoma
      volume showed a linear correlation (p=0.00). Moreover, positive correlation
      between edema intensity and rCBV was detected, (p=0.00); the most significant
      perihematoma edema was in the group of day 10 to day 14; the lowest rCBV occurred
      in the early stage. (days 2-5 from symptom onset). CONCLUSION: We have concluded
      that rCBV and MTT of perihematoma region decreased remarkably compared with the
      contralateral side, and the decline would last over 3 weeks. Quantitative
      research suggested edema intensity is closely related with rCBV. We believe that
      the reduced regional blood flow of perihematoma contributes to the secondary
      ischemic injury of perihematoma tissue. However, the peak of edema would appear
      later than the onset of the peak of ischemia, it suggests that edema surrounding
      the hematoma is not only the result from the single ischemic factor, but also
      results from multiple disadvantage mechanisms.

PMID- 16464366
TI  - Expression of cytoskeleton and apoptosis related genes after cerebral infarction.
AB  - OBJECTIVE: The aim of the study was to investigate the expression and regulation
      of cytoskeleton and apoptosis related genes in several brain areas after cerebral
      infarction. METHODS: Tissues were collected from ten autopsy brains from cerebral
      infarction patients. Using immunohistochemistry, several cytoskeleton and
      apoptosis related genes were examined in these tissues. The genes included
      microtubule-associated protein (MAP), glial fibrillary acidic protein (GFAP),
      neurofilament protein (NF-200), apoptosis gene bc1-2 and factor VIII related
      antigen (F-VIII). Based on morphological changes in the damaged areas after
      infarction, the focus and the surrounding areas of injured brain were divided
      into four areas. RESULTS: In area 0, there was almost no cell survival after
      infraction, and all markers mentioned above were negative in this area. In
      addition, both MAP-2 and NF200 like immunoreactivities were dramatically down
      regulated in area 1. However, in area 2 and area 3, MAP-2 and NF-200 expressed at
      normal level. GFAP- and F-VIII immunoreactive cells could hardly found in areas 0
      and 1. In the short phase of ischemia, both GFAP and F-immmunoreactive cells
      could be seen in areas 2 and 3, and the number of GFAP and F (positive cells) was
      strongly increased in the long phase of ischemia. Bcl-2 immunoreactive cells were
      only seen in area 2. CONCLUSION: Cerebral infarction causes cell death and
      physipathological changes of cytoskeleton and apoptosis related genes.

PMID- 16464367
TI  - Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis.
AB  - BACKGROUND AND PURPOSE: Analysis of dynamic cerebral autoregulation during
      transient falls in blood pressure is considered a sensitive and convenient method
      for evaluating patients with carotid artery stenosis. To this point, there have
      been few reports on the efficacy of using the thigh cuffs technique to analyse
      middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral
      blood flow can be maintained (autoregulated) during sudden falls in arterial
      blood pressure (ABP), then it might be possible to identify patients with MCA
      stenosis who are at risk of stroke. METHODS: We used the thigh cuff technique to
      estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72
      normal controls. After a stepwise fall in arterial blood pressure, we determined
      the rate of the rise of MCA blood velocity and compared it with the rate of the
      rise of arterial blood pressure. In this manner, the dynamic cerebral
      autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated
      both pre- and post-operation. RESULTS: The autoregulatory index (ARI) was
      significantly reduced in patients with stenosed/occluded MCA (3.24 +/- 1.52), as
      compared with normal controls (5.25 +/- 1.39; p<0.001) (results reported as mean
      +/- SD). Poor ARI values are usually observed in patients with a higher degree of
      stenosis and particularly in patients with insufficient collateral compensation.
      ARI was significantly reduced in severe stroke patients (modified ranking
      scale>or=1), as compared with asymptomatic or TIA patients (p<0.05). After MCA
      stent angioplasty was performed, there was a significant improvement in ARI in 11
      subjects, which caused a mean increase in ARI from 2.08 +/- 1.10 to 3.80 +/- 1.36
      (p=0.008). CONCLUSIONS: Dynamic cerebral autoregulation is impaired in patients
      with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation
      may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic
      stroke to be identified. Dynamic cerebral disautoregulation in patients with
      severe MCA stenosis is mostly remedied by stent angioplasty.

PMID- 16464368
TI  - Establishment of a porcine model of patent foramen ovale.
AB  - OBJECTIVE: To investigate the feasibility of developing an animal model of patent
      foramen ovale (PFO) in piglets by percutaneous atrial septal puncture and balloon
      dilation. METHODS: A standardized percutaneous atrial trans-septal puncture and
      balloon dilation was conducted in 11 healthy piglets under general anesthesia. A
      Rups-100 system inserted through a femoral vein was used for the transseptal
      puncture, and subsequent balloon dilatation was performed at the puncture site to
      imitate a PFO. Euthanasia and autopsy were performed on day 1 in one piglet
      (early autopsy), and on day 21 in the remaining ten piglets (late autopsy).
      RESULTS: Artificial PFO was successfully created in all piglets and verified by
      fluoroscopy. No major technical difficulty or complication was encountered except
      in one which developed mild hemopericardium. In the piglet that had early
      autopsy, the artificial foramen was measured 0.8 x 0.7 cm(2) in cross-section and
      aggregates of erythrocytes were revealed over its rim under light microscopy. In
      the late autopsy group (n=10), seven piglets had the created foramens healed and
      sealed off, while the other three showed relatively small residual lumens
      measured 0.1 x 0.2 cm(2), 0.2 x 0.2 cm(2) and 0.1 x 0.3 cm(2) in cross-section,
      respectively. Histological examination of specimens from the late autopsy group
      showed variable neointima hyperplasia, cardiac muscle necrosis and focal fibrosis
      at the puncture site, regardless of the course of healing. CONCLUSION: Artificial
      creation of PFO in piglets is feasible by percutaneous atrial septal puncture and
      balloon dilation. This protocol may serve as a research model for PFO-related
      stroke in human.

PMID- 16464369
TI  - bFGF and heparin but not laminin are necessary factors in the mediums that affect
      NSCs differentiation into cholinergic neurons.
AB  - OBJECTIVES: Neural stem cells (NSCs) are self-renewed, pluripotent cells that can
      differentiate into neurons, astrocytes and oligodendrocytes. Cholinergic neurons
      are an important kind of neurons that play an essential role in the treatment of
      Parkinsonism and epilepsy. We are interested in how different mediums affect NSCs
      differentiation into cholinergic neurons. METHODS: NSCs were isolated from the
      striatum corpora of embryonic brain in a 14-day pregnant rat. Cells were cultured
      in basic mediums [F12/DMEM (1:1) including 1% B27 (v/v) and 20 ng/ml EGF] but
      with different combinations of three supplements: bFGF (20 ng/ml), heparin (5
      mug/ml) and laminin (1 mug/ml). After 7 days culturing, cells were immunized with
      choline acetyltransferase (ChAT), a marker enzyme of cholinergic neuron. RESULTS:
      We found ChAT could not be detected in the basic mediums with only one
      supplement. Then, we tested the combination of two out of three. We found that
      ChAT positive cells could only be detected in the medium with bFGF and heparin
      (FH). However, when we added the laminin into the FH, more ChAT positive cells
      appeared. DISCUSSION: This finding suggests that bFGF and heparin are essential
      in the mediums that affect NSCs differentiation into cholinergic neurons, and
      laminin is an important positive factor in this process.

PMID- 16464370
TI  - Cell proliferation in ependymal/subventricular zone and nNOS expression following
      focal cerebral ischemia in adult rats.
AB  - Neuronal nitric oxide synthase (nNOS) regulates neurogenesis in normal developing
      brain, but the role of nNOS in neurogenesis in the ischemic brain remains
      unclear. To investigate the temporal and spatial relationship between cell
      proliferation of the ependymal/subventricular zone (SVZ), a principal
      neuroproliferative region in the adult brain, and nNOS expression, the male
      Sprague-Dawley rats weighing 250-350 g were used. The focal cerebral ischemia was
      induced by middle cerebral artery occlusion (MCAO). 10 microl of 0.2%
      fluorescence dye DiI was injected into the right lateral ventricle to prelabel
      ependymal/subventricular zone cells before ischemia. The rats were killed
      immediately after ischemia and days 1, 3, 7, 11, 14, 21 and 28 after ischemia.
      DiI-labeled cell counting was employed to assess cell proliferation.
      Immunohistochemistry and grayscale analysis were performed to determine nNOS
      localization and its quantity in the specific regions. Compared with control, the
      density of DiI-labeled cells in the ipsilateral ependyma/SVZ was significantly
      higher at days 1, 3, 7 and 11 after ischemia, whereas the quantity of nNOS
      expression in the ependyma/SVZ adjacent regions was significantly lower at the
      above time points. Additionally, nNOS positive cells were largely excluded from
      SVZ, and their long processes did not enter the ependyma/SVZ. Our results
      indicate that after focal cerebral ischemia, decreased nNOS expression in the
      ipsilateral ependymal/SVZ adjacent regions might be related to cell proliferation
      in the ependymal/SVZ.

PMID- 16464371
TI  - Effect of acupuncture treatment on vascular dementia.
AB  - OBJECTIVE: Recent studies have suggested that acupuncture can ameliorate some
      symptoms commonly associated with vascular dementia (VaD). The study was carried
      out to observe the clinical therapeutic effects for VaD of 'yi qi tiao xue, fu
      ben pei yuan' acupuncture method (supplementing vital force-matter and regulating
      blood, supporting the root and fostering the source). METHODS: Sixty inpatients
      with VaD were randomly assigned to the treat group (TG) or control group (CG).
      Both the TG and the CG received routine treatment as other inpatients with VaD,
      including medication and traditional acupuncture treatment. After that, the TG
      was given the treatment of 'yi qi tiao xue, fu ben pei yuan' acupuncture, which
      included five body acupoints, namely, tanzhong (CV17), zhongwan (CV12), qihai
      (CV6), zusanli (ST36) and xuehai (SP10). The Treatment was performed once daily
      for 6 weeks. The mini-mental status examination (MMSE), the revised Hasegawa's
      dementia scale (HDS-R) and activities of daily living (ADL) exam were carried out
      before and after the experiment, to evaluate therapeutic effects of the
      acupuncture method. RESULTS: The MMSE, HDS-R and ADL scores were significantly
      improved in the TG and CG (p<0.001). But the overall scores of MMSE and HDS-R for
      the subjects in the TG were notably higher than those in the CG (p<0.05).
      Patients in the TG showed remarkable improvement in memory, orientation,
      calculation and self-managing ability in daily living after treatment. The total
      effective rate was 80.0% in the TG versus 46.7% in the CG, where significant
      difference between the two groups exhibited (p<0.05). CONCLUSIONS: These results
      suggested that 'yi qi tiao xue, fu ben pei yuan' acupuncture method had
      significant therapeutic effects and well tolerated in ameliorate the key clinical
      symptoms of VaD.

PMID- 16464372
TI  - Differentiation and neurological benefit of the mesenchymal stem cells
      transplanted into the rat brain following intracerebral hemorrhage.
AB  - Spontaneous intracerebral hemorrhage (ICH) is often a fatal event. In a patient
      who survives the initial ictus, the resulting hematoma within brain parenchyma
      can trigger a series of events that lead to secondary insults and severe
      neurological deficits. Great efforts have been focused on searching for new
      approaches to help patients recover neurological function after ICH. Previous
      studies indicate that mesenchymal stem cells (MSCs) grafted into the ischemic rat
      brain can improve neurological function. However, there is no report regarding
      whether MSCs can be used in the same way to improve the neurological function
      after ICH. We generated the ICH model by injecting collagenase VII into rat
      brain. Subsequently, 5-bromo-2-deoxyuridine (BrdU)-labeled mesenchymal stem cells
      were delivered into the brain through carotid artery, cervical vein or lateral
      ventricle. The distribution and differentiation of MSCs were investigated by
      methods of immunohistochemistry. We found that MSCs were able to differentiate
      into neural cells in vitro as well as in the rat brain after ICH. The injected
      MSCs were able to migrate into hippocampus, blooding foci and ipsilateral cortex.
      In the hippocampus, MSCs differentiated into neurons; but in surrounding bleeding
      foci, they differentiated into neurons and astrocytes. In the ipsilateral cortex,
      MSCs differentiated into neurons, astrocytes and oligodendrocytes. Notably, the
      motor function of the rats in the carotid artery (CA) group and the lateral
      ventricle (LV) group improved significantly. Collectively, our study indicates
      that MSCs are able to differentiate into neural cells in the rat brain after ICH
      and can significantly improve motor function.

PMID- 16464373
TI  - [Guide of emergency medicine on the basis of evidence based medicine].

PMID- 16464374
TI  - [Effects of hypertonic saline on expression of heme oxygenase enzyme-1 in hepatic
      ischemia/reperfusion injury rats].
AB  - OBJECTIVE: To explore the effect of the pretreatment with hypertonic saline (HTS)
      in the hepatic ischemia/reperfusion (I/R) injury. METHODS: Twenty-five SD rats
      were randomly divided into sham operation group, heme oxygenase-1 (HO-1) blocker
      ZnPP group, I/R group, HTS pretreatment group and ZnPP intervention group (n=5).
      The rat model of partial hepatic I/R injury was reproduced by isolating the
      portal venous and hepatic arterial branches to the left and median hepatic lobes,
      and they were occluded with a microvascular clamp for 30 minutes, followed by
      reperfusion. In HTS pretreatment group, the rats received 4 ml/kg volume of HTS
      (7.5%) intravenous 1 hour before the occlusion of the vessels. The rats were
      sacrificed 6 hours after reperfusion. The levels of alanine aminotransferase
      (ALT) and tumor necrosis factor-alpha (TNF-alpha) in serum, liver myeloperoxidase
      (MPO) activity and liver endothelin-1 (ET-1) were determined. Reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot were used to
      examine the expression of HO-1 in the liver. The pathological changes in the
      liver, including hepatic sinusoid, were evaluated in hematoxylin and eosin (HE)
      stained sections and transmission electron microscopy (TEM) of liver specimens.
      The effect of HTS pretreatment was also assessed in the rats pretreated with
      ZnPP. RESULTS: The levels of serum ALT and TNF-alpha, ET-1 and MPO activity in
      hepatic tissues increased after hepatic I/R injury (all P<0.01), and expression
      of HO-1 mRNA and protein were also increased. RT-PCR and Western-blot revealed
      that the expression of HO-1 in the liver was upgraded significantly, and the ALT
      level, serum TNF-alpha, liver MPO activity and liver ET-1 were suppressed
      significantly after I/R injury in the HTS pretreatment group. In this group,
      there were moderate swelling of hepatocytes and mild neutrophils infiltration in
      the liver. The hepatic microcirculatory dysfunction was ameliorated. All these
      findings showed that HTS pretreatment produced the effect of prevention on
      hepatic I/R injury. However, the adjunctive infusion of ZnPP abrogated the
      beneficial effects. CONCLUSION: Pretreatment of HTS has the effect of the
      prevention of hepatic I/R injury by promotion of the expression of HO-1.

PMID- 16464375
TI  - [Effect of acidic fibroblast growth factor on mitogen-activated protein kinase
      activity in small intestinal epithelium after ischemia/reperfusion injury in
      rat].
AB  - OBJECTIVE: To investigate the effect of acidic fibroblast growth factor (aFGF) on
      p44/p42 mitogen-activated protein kinase (p44/p42 MAPK, extracellular signal
      regulated protein kinase, ERK1/2) activity in small intestinal epithelium in rat
      after ischemia/reperfusion (I/R) injury and its relation with the change in small
      intestinal epithelium in rat after I/R injury as well as the change in
      proliferation of epithelial cells. METHODS: Superior mesenteric artery (SMA) was
      occluded to produce ischemia of the intestine for 45 minutes followed by
      reperfusion to reproduce I/R injury. One hundred and thirty-two Wistar rats were
      randomly divided into sham-operation group, I/R group, aFGF treatment group (4
      microg of aFGF was injected into jugular vein after reperfusion), and PD98059
      (antagonist of ERK 1/2) pretreatment group (7.5 microg of PD98059 was injected
      via tail vein before ischemia and 4 microg of aFGF was injected via jugular vein
      after reperfusion). The activity of ERK1/2 and proliferation rate of small
      intestinal epithelial cells were determined before ischemia and 15 minutes, 30
      minutes, 1 hour, 2 hours, 6 hours, 12 hours and 24 hours after reperfusion.
      RESULTS: The activity of ERK1/2 in small intestinal epithelium was higher in aFGF
      treatment group than in I/R control group, and the proliferation rate in small
      intestinal epithelial cells was significantly enhanced in aFGF treatment group.
      PD98059, the specific inhibitor of ERK1/2, inhibited ERK1/2 activity and reduced
      the proliferation rate of small intestinal epithelial cells in aFGF treatment
      group. CONCLUSION: aFGF can promote small intestinal epithelial cell
      proliferation in I/R injury rats, and this may be related to activation of ERK1/2
      in small intestinal epithelium.

PMID- 16464377
TI  - [Clinical study on bacterial translocation in severe multiple trauma patients].
AB  - OBJECTIVE: To investigate bacterial translocation in severe multiple trauma
      patients using polymerase chain reaction (PCR) to detect the presence of bacteria
      in the blood. METHODS: Sixteen severe multiple trauma patients [injury severity
      score (ISS)>20] in surgery intensive care unit (SICU) were selected. Blood
      samples were collected 2, 24 and 48 hours after trauma for bacterial culture and
      microbial DNA detection. Meanwhile, plasma levels of D-lactate and
      lipopolysaccharide (LPS) in systemic circulation were determined. PCR was
      performed after DNA extraction, with target beta-lactosidase gene of E. coli and
      16SrRNA gene of most pathogenic bacteria. All patients were observed within 30
      days for infectious complications. D-lactate and LPS levels were determined in 63
      patients before selective operation. RESULTS: Microbial DNA could be detected in
      blood as early as 2 hours following severe trauma, and altogether positive
      results were found in 10 patients (62.50%). All PCR-positive patients manifested
      sepsis, but none of the PCR-negative patients did (P<0.01). Bacterial DNA was
      discovered in 100.00% of sepsis patients and none in non-sepsis patients
      (P<0.01). Seventy percent of PCR-positive patients developed infectious
      complications, while none of PCR-negative patients did (P<0.01). The blood
      culture was positive only in 3 patients (18.75%), all of them were PCR-positive.
      E.coli DNA was found in 70.00% of all the PCR positive blood specimens. Systemic
      plasma concentration of D-lactate and LPS of all patients was significantly
      higher than that in control group, which consisted of 63 inpatients waiting for
      elective operations. Systemic plasma level of D-lactate showed a positive
      correlation with that of LPS (r=0.94, P<0.01). CONCLUSION: Intestinal bacterial
      translocation (most commonly E. coli) might occur early (2 hours) after severe
      trauma. Infection and sepsis have a close relationship with bacterial
      translocation. Detection of blood microbial DNA using PCR could reflect bacteria
      translocation and forecast imminent infection and sepsis.

PMID- 16464378
TI  - [Effects of Xuebijing injection on multiple organ dysfunction and mortality in
      rats with delayed resuscitation for scald injury].
AB  - OBJECTIVE: To investigate the effects of Xuebijing injection on multiple organ
      dysfunction and mortality in rats with delayed resuscitation after scald injury.
      METHODS: Wistar rats were subjected to a 30% total body surface area (TBSA) full
      thickness scald injury in the experimental groups. One hundred and thirty male
      Wistar rats were randomly divided into sham scald group (n=10), thermal injury
      group (n=60, 40 ml/kg normal saline was infused peritoneally 6 hours postburn),
      and Xuebijing treatment group (n=60, 4 ml/kg Xuebijing injection was injected
      twice a day in addition to delayed resuscitation). Animals of the thermal injury
      group and Xuebijing treatment group were re-divided into three subgroups
      according to the different time points of treatment: 2 hours before scald (n=20),
      2 hours after scald (n=20), and 12 hours after scald (n=20). Multiple organ
      function parameters and 7-day mortality were determined in all the groups.
      RESULTS: The mortality of animals with Xuebijing treatment at 12 hours postburn
      was significantly lower than that of scald controls (75.0% vs. 40.0%, P<0.05). In
      comparison with scald group, the animals in Xuebijing treatment group were found
      to have significantly decreased values of organ functional parameters at 12 hours
      postburn, including serum levels of alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr) and creatine
      kinase (CK, P<0.05 or P<0.01). CONCLUSION: These findings indicate that Xuebijing
      injection could obviously lower the mortality of rats with delayed resuscitation
      after burn injury, and it markedly protects against multiple organ dysfunction
      secondary to severe burns.

PMID- 16464379
TI  - [Effect of long tubular bone fracture on serum levels of leptin, acute phase
      proteins and biochemical markers for organ functions].
AB  - OBJECTIVE: To investigate the effect of long tubular bone fracture (LTBF) on
      serum levels of leptin, acute phase proteins and biochemical markers for organ
      functions, and to look for the role of leptin in traumatic inflammatory
      responses. METHODS: Serum samples of LTBF patients and normal controls were
      collected, and immunoassays were used to determine serum levels of leptin and
      three acute phase proteins, including C-reactive protein (CRP), interleukin-1 (IL
      1) and IL-2, and 21 biochemical markers for organ and metabolic functions were
      measured simultaneously with automatic biochemical analyzer. Correlation between
      leptin and all the markers was then analyzed. RESULTS: Compared with normal
      control, serum levels of leptin, CRP, IL-1 and IL-2 increased significantly (all
      P<0.05), with various degrees of changes in the markers for hepatic, cardiac,
      renal and metabolic functions. Leptin was independent to all the markers
      investigated, and it seemed to exert its unique roles. CONCLUSION: Leptin
      increases significantly in LTBF-induced acute traumatic inflammatory response,
      showing a comparatively strong responsiveness to the stimulation, and it may play
      a role as an anti-inflammatory cytokine.

PMID- 16464381
TI  - [Changes in spleen dendritic cells in multiple organ dysfunction syndrome in
      mice].
AB  - OBJECTIVE: To explore the pathological features of the splenic dendritic cells
      (DCs) and their role in the pathogenesis of multiple organ dysfunction syndrome
      (MODS). METHODS: The MODS model of mice was reproduced. The changes in DCs in the
      spleen in mice with MODS were studied using light microscope, electronic
      microscope, immunohistochemistry (CD205, CD86) and transferase mediated dUTP
      biotin nick end labeling (TUNEL). RESULTS: In the early stage (3 hours), there
      was hyperplasia with increased activity of DCs in the spleen, accompanied by
      apoptosis of a large number of lymphocytes. CD4(+)/CD8(+) ratio declined in the
      peripheral blood. In the MODS stage (10-12 days), the number of DCs increased but
      with declined function. CD4(+)/CD8(+) ratio declined markedly in peripheral
      blood. CONCLUSION: During the course of MODS, changes in the number and activity
      of DCs in spleen are very important in the establishment of immune response and
      maintenance of immune function.

PMID- 16464382
TI  - [Changes in tumor necrosis factor-alpha mRNA expression in peripheral
      polymorphonuclear leukocyte and tissues during posttraumatic sepsis].
AB  - OBJECTIVE: To evaluate the changes in tumor necrosis factor-alpha (TNF-alpha)
      mRNA expression in peripheral polymorphonuclear leukocyte (PMNs) and tissues
      after cecal ligation puncture (CLP) in rats. METHODS: Reverse transcription
      polymerase chain reaction (RT-PCR) was used to detect TNF-alpha mRNA expression
      in peripheral PMNs and tissues. RESULTS: The TNF-alpha mRNA expression in
      peripheral PMNs rose gradually after CLP, and it began to decrease after reaching
      the peak at 48 hours, but it was still higher than normal. The elevation of TNF
      alpha mRNA expression was first limited in the regional tissues (P<0.01 at 12
      hours after CLP and peaked at 24 hours in the intestine), then it entered the
      blood circulation later to affect the sensitive organs--lungs and livers (P<0.01
      at 24 hours after CLP and peaked at 48 hours in the lung; P<0.05 at 24 hours
      after CLP and peaked at 48 hours in the liver). CONCLUSION: The rise of TNF-alpha
      mRNA expression plays an important role in pathogenesis of sepsis.

PMID- 16464383
TI  - [Effect of intravenous patient-controlled intravenous analgesia with small dose
      of ketamine during shock stage on cytokine balance in patients with severe burn].
AB  - OBJECTIVE: To investigate the influences of patient-controlled intravenous
      analgesia (PCIA) with small dose of ketamine solely or combined with fentanyl
      during shock stage on cytokine balance in patients with severe burn. METHODS:
      Forty-five patients with severe burn and hospitalized within 24 hours after
      injury were randomly divided into three groups (n=15 in each group): conventional
      analgesia therapy group (group CAT), patient controlled intravenous ketamine
      analgesia group (group PCIKA, intravenous small dose ketamine), and patient
      controlled intravenous ketamine and fentanyl analgesia group (group PCIKFA,
      intravenous small dose ketamine combined with fentanyl). In group CAT, patients
      received intramuscular injection of pethidine 50 mg and phenergan 25 mg when
      patients complained of pain. In group PCIKA, patients received intravenous
      infusion with a mixture of ketamine 20 g/L + droperidol 50 mg/L, and in group
      PCIKFA with a mixture of ketamine 10 g/L + fentanyl 5 mg/L + droperidol 50 mg/L.
      In two groups of PCIA, patients received loading dose of 1 ml, with background
      infusion of 1.5 ml/h. Pain scores and side effects of analgesics were determined
      or observed at the time points of before analgesia and 1, 8, 24, 48 hours after
      analgesia, and serum cytokines [including interleukin-1 (IL-1), IL-6, tumor
      necrosis factor-alpha (TNF-alpha)] were measured at the same time points.
      RESULTS: Pain scores in PCIFA and PCIKFA groups were significantly lower than
      that of before analgesia and group CAT (all P<0.01). There were no significant
      differences in heart rate (HR) and mean artery pressure (MAP) in three groups. No
      significant difference in side effects was found in three groups. The serum
      levels of cytokines were significantly lower in two PCIA groups than those of
      group CAT (all P<0.01). CONCLUSION: Patient-controlled intravenous analgesia with
      small doses of ketamine or combined with fentanyl during shock stage in patients
      with severe burn give efficient and safe pain relief, and cytokine balance.

PMID- 16464385
TI  - [Relationship between trauma score and complications and interventions of
      traumatic patients in department of emergency medicine].
AB  - OBJECTIVE: To investigate the relationship between trauma score (TS) and
      complications and interventional strategies in trauma patients in the Emergency
      Department. METHODS: The injury severity was assessed with TS, and complications
      were recorded in 1 826 trauma patients in Emergency Department. The
      interventions, monitoring and imaging examinations were initiated promptly.
      RESULTS: The TS ranged from 1 to 16 points, and the lower the TS the poorer the
      patient's condition. The patients with score of 10 or above accounted for 73.06%
      of patients, those with score of 10 or below accounted for 26.94%. When they left
      Emergency Department in 91.84% of the patients TS was above 10, while 8.16% of
      them TS was 10 or below (both P<0.001). The patients with score of 10 or below
      had a higher rate of severe complications including hypotension, shock, abnormal
      respiration, and cardiac arrest. The lower the TS, the larger the amount of fluid
      resuscitation required. CONCLUSION: TS provides an objective value to indicate
      the seriousness of the patient's condition, and it is valuable to the attending
      to plan the strategies of intervention, monitoring and necessary instrumental
      examinations.

PMID- 16464386
TI  - [Protective effects of urinastatin on organ function in patients with severe
      burn].
AB  - OBJECTIVE: To investigate the protective effects of urinastatin on organ function
      in severe burn. METHODS: Seventy-two cases with comparative severity in burn
      injury were randomly divided into urinastatin treatment group (n=36) and control
      group (n=36). Patients in control group received routine therapy, while those in
      treatment group received intravenous dripping of urinastatin twice a day for 5 to
      7 days. The dosage of urinastatin was 300 kU in severe burns and 200 kU in
      moderate burns. Both polyvinylpyrrolidone iodine (PVP-I) and Jiedu Shaoshang
      cream were used for wound dressing. The clinical findings were assessed and
      variables indicating functions of internal organs, including liver (alanine
      aminotransferase), kidney (blood urea nitrogen, serum creatinine), heart
      (aspartate aminotransferase, lactate dehydrogenase, alpha-hydroxybutyrate
      dehydrogenase, creatine kinase, isoenzymes of creatinine kinase), and coagulation
      (prothrombin time, international normalized ratio, activated partial
      thromboplastin time, fibrinogen), as well as blood routine test, troponin,
      myoglobin, arterial blood analysis, bacteria culture were measured. RESULTS: In
      treatment group, vital signs and general condition were satisfactory at shock
      phase and peri-operative stages in all the patients. Edema of burn wound subsided
      rapidly. The 28-day mortality rate was 0. There was significant difference
      between the two groups (all P<0.05). CONCLUSION: Urinastatin has protective
      effects on multiple organs in severe burn injury.

PMID- 16464387
TI  - [Experiment study of enteral immuno-nutrition combined with recombinant human
      growth hormone in treatment of severe scald in rats].
AB  - OBJECTIVE: To investigate the effects of enteral immuno-nutrition (EIN) combined
      with recombinant human growth hormone (rhGH) on nutrition metabolism,
      immunological function and inflammatory response in rats with severe scald.
      METHODS: Sixty-four SD rats subjected to 30% total body surface area (TBSA) III
      degree scalds were randomly divided into EIN and EIN combined with recombinant
      human growth hormone (EIN+rhGH) groups. Animals of both groups were fed
      isocaloric enteral nutrition. Nutrition metabolism, T lymphocyte subsets, serum
      levels of immunoglobulins and inflammatory mediators were determined on the 1, 4,
      7 and 10 postinjury day (n=8). Another 8 rats served as controls, and the above
      mentioned parameters were also determined. RESULTS: Total protein (TP), albumin
      (Alb), transferrin protein (TFP), CD3(+), CD4(+), CD4(+)/CD8(+), IgG, IgM and IgA
      in group EIN+rhGH were slightly higher than those of group EIN (all P>0.05) at
      all time points after the injury, while CD8(+) slightly lowered (P>0.05). Serum
      levels of lipopolysaccharide (LPS), interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) plummeted significantly (P<0.05 or P<0.01)on 4th, 7th
      and 10th postinjury day compared with group EIN. CONCLUSION: Our findings
      indicate that EIN combined with rhGH is superior to EIN alone in the early stage
      of severe scald in rats, not only ameliorate the disturbance in metabolism and
      immunological function, but also reduce inflammatory response.

PMID- 16464388
TI  - [Isolation, culture and identification of adult epidermal stem cell].
AB  - OBJECTIVE: To explore and establish a new method of isolation, culture, and
      identification of adult epidermal stem cell in vitro for the provision of seed
      cells in tissue engineering of skin. METHODS: Epidermis was obtained by digesting
      human foreskin with protease and it was dissociated into single cells with
      trypsin and ethylenediaminetetraacetic acid (EDTA). These single epidermis cells
      were inoculated onto human collagen IV coated flasks and cultured at 37 degrees C
      in a humidified atmosphere containing 5% CO(2). The nonadherent cells were rinsed
      off 10-15 minutes after inoculation. The adherent cells were observed under phase
      contrast microscope and electron microscope, and they were identified with
      immunocytochemical methods. Cell cycles of the adherent cells were determined
      with flow cytometry. RESULTS: With phase contrast microscope, the rapidly
      adherent cells were observed to form colonies 24 hours after inoculation.
      Immunocytochemistry showed the rapidly adherent cells were positive for beta1
      integrin and keratin 19. Cell cycles showed that about 86.83% cells were in
      resting state/pre-DNA-synthetic gap (G0/G1 phase). Electron microscopy revealed
      that the rapidly adherent cells were immature. CONCLUSION: This study shows that
      adult epidermal stem cells could be isolated and cultured in vitro successfully.

PMID- 16464389
TI  - [Preliminary study on outcome of xenogeneic (porcine) acellular dermal matrix in
      vivo].
AB  - OBJECTIVE: To investigate the outcome of xenogeneic (porcine) acellular dermal
      matrix in vivo. METHODS: Xenogeneic (porcine) acellular dermal matrix was
      prepared by removing cellular components with trypsin and triton X-100 and was
      embedded under the skin of SD rat. Gross and histological changes were observed
      periodically. RESULTS: There was no cellular components but with intact basal
      membrane, and collagen was found to have a regular arrangement in xenogeneic
      (porcine) acellular dermal matrix. Grossly, the xenogeneic (porcine) acellular
      dermal matrix was found to disintegrate gradually. Histological examination
      revealed that xenogeneic (porcine) acellular dermal matrix was mainly infiltrated
      by inflammatory cells in one week after implantation. After one week, fibroblasts
      and capillary vessel increased in number gradually, and collagen began to arrange
      densely in regular manner. CONCLUSION: Xenogeneic (porcine) acellular dermal
      matrix disintegrates gradually after transplantation, inducing growth of
      fibroblasts and capillaries.

PMID- 16464390
TI  - [Comparison of effects of low-dose dopamine and dobutamine in patients with
      nonoliguric renal failure].
AB  - OBJECTIVE: To investigate the effects of low-dose dopamine and dobutamine on
      renal functioning patients with nonoliguric renal failure. METHODS: Twenty-nine
      hemodynamically stable patients with nonoliguric renal failure were enrolled to
      this study group. Each patient was given 5% glucose (control), dopamine or
      dobutamine in random order by means of an injection pump every 4 hours. The
      change in urine output, fractional excretion of sodium (FeNa) and creatinine
      clearance rate (CCr) were determined. RESULTS: Compared with control, urine
      volume, FeNa, and CCr were increased significantly after administration of
      dopamine, or dobutamine. Compared with dobutamine, dopamine could increase the
      urine output and the FeNa markedly, but there was no difference in CCr increase
      between dopamine and dobutamine. CONCLUSION: Dopamine or dobutamine treatment
      could significantly increase the urine output, FeNa, and CCr in patients with
      nonoliguric renal failure. Dopamine infusion markedly increases urine output and
      the FeNa, but there is no significantly difference in CCr between dopamine and
      dobutamine treatment.

PMID- 16464396
TI  - Turning cervix cancer into a "rare disease": is society prepared to do what is
      required to make this a reality?

PMID- 16464397
TI  - Advances in breast imaging: magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) of the breast is rapidly becoming incorporated
      into clinical practice. Indications for breast MRI include staging of known
      breast cancer, monitoring response to chemotherapy, assessing recurrence, problem
      solving, and high-risk screening. Magnetic resonance spectroscopy is a promising
      technique that may decrease the number of benign biopsies generated by breast MRI
      in the clinical setting.

PMID- 16464398
TI  - Update on hereditary breast cancer.
AB  - Women with BRCA1 or BRCA2 mutations are at substantial risk for breast and
      ovarian cancer. This review describes recent developments in the approach to
      hereditary breast cancer. Risk-reducing surgeries remain the most effective means
      of preventing breast cancer in mutation carriers. For women with breast tissue at
      risk, magnetic resonance imaging is rapidly becoming incorporated into screening
      programs. For affected women, management does not currently differ from that of
      women with sporadic breast cancer, although women may choose to undergo bilateral
      mastectomy. Preclinical data suggest that BRCA mutation-associated breast cancers
      may benefit from specific targeted therapeutic approaches.

PMID- 16464399
TI  - Bone integrity and bone metastases in breast cancer.
AB  - Individuals with a history of early-stage breast cancer may be at increased risk
      of osteoporosis related to adjuvant therapy, and those with metastatic breast
      cancer may experience skeletal-related complications from the cancer affecting
      the bone. Maintaining bone strength is critical in the care of both early- and
      late-stage breast cancer patients because fractures are associated with morbidity
      and mortality. This article reviews the maintenance of bone integrity in women
      with breast cancer.

PMID- 16464400
TI  - Postmastectomy radiotherapy in intermediate-risk patients: the gray zone.
AB  - Postmastectomy radiotherapy continues to be one of the most controversial issues
      in breast radiotherapy. At the crux of the controversy lies the lack of
      conclusive studies that specifically address the risk-benefit ratio of
      postmastectomy radiotherapy for patients at intermediate risk of developing
      locoregional recurrence. A well-designed phase III trial was initiated, but the
      trial failed to accrue and was closed prematurely, leaving the issue unresolved.
      Recent data confirm that postmastectomy radiotherapy yields a clear benefit in
      breast cancer-specific survival. Furthermore, the risk of cardiac morbidity that
      historically has offset the benefit of postmastectomy radiotherapy appears to be
      lessening with modern radiotherapy approaches. However, newer, more efficacious
      systemic therapy regimens may decrease the risk of locoregional recurrence and
      increase the risk of toxicity from combined-modality therapy. Recent studies
      attempt to better stratify patients into risk categories based on disease factors
      and to estimate the benefit of postmastectomy radiotherapy when traditional risk
      estimates, such as nodal status, are obscured by neoadjuvant systemic therapy.
      Nonetheless, a clear consensus on the role of postmastectomy radiotherapy remains
      elusive for patients who are at intermediate risk of locoregional recurrence
      after mastectomy.

PMID- 16464401
TI  - Update on accelerated partial-breast irradiation.
AB  - Progress in radiotherapy technology, particularly the advent of CT-guided
      simulation and three-dimensional conformal planning, has given the radiation
      oncologist the ability to precisely treat part of the breast, instead of the
      whole breast, using either brachytherapy or external-beam techniques. Treating
      such a limited area may allow the course of treatment for patients with early
      stage breast cancer to be drastically shortened and could reduce toxicity to
      other organs. This article summarizes the rationale for accelerated partial
      breast irradiation (APBI), techniques for performing it, and outcome to date of
      studies of APBI.

PMID- 16464402
TI  - Advances in the treatment of primary brain tumors: dawn of a new era?
AB  - The prognosis for patients with malignant primary brain tumors has been poor, and
      until recently, there was little evidence that chemotherapy was beneficial. The
      publication of the phase III trial comparing the combination of temozolomide with
      external beam radiation therapy with radiation therapy alone demonstrated a clear
      survival benefit for the combination regimen. These results, along with
      improvements in clinical trial design and outcome assessment, advances in our
      understanding of glioma tumor biology, and recognition of critical drug-drug
      interactions, have provided a foundation for developing better treatments for
      these cancers.

PMID- 16464403
TI  - The evolution of chemoradiation for glioblastoma: a modern success story.
AB  - The dismal prognosis of glioblastoma had remained unchanged for the past 30 years
      until the association of temozolomide and radiotherapy in the breakthrough
      European Organization for Cancer/National Cancer Institute of Canada (EORTC/NCIC)
      trial brought new hope for patients. This trial will serve as a platform for new
      and exciting clinical and translational research areas. We review here the role
      of standard radiotherapy and chemotherapy in glioblastoma and the potential
      causes of their failure, and we focus on some of the aspects that led to the
      successful EORTC/NCIC trial and some of the related studies.

PMID- 16464404
TI  - Correlative studies in neuro-oncology trials: should they influence treatment?
AB  - Recent molecular correlative studies accompanying clinical trials in glioma have
      provided strong evidence for prognostic markers and predictive factors for
      treatment response. However, to what extent can these markers influence the
      limited choice of therapeutic options? Do we further validate the markers in the
      next trials or move on, incorporate the markers for patient selection or
      stratification, aim at improving the modestly effective treatments by adding new
      drugs, and develop alternative therapy strategies for patients selected for their
      bad predictor?

PMID- 16464405
TI  - Targeted molecular therapy of malignant gliomas.
AB  - Malignant gliomas are the most common form of primary brain tumors in adults.
      Despite advances in diagnosis and standard therapies such as surgery, radiation,
      and chemotherapy, the prognosis remains poor. Recent scientific advances have
      enhanced our understanding of the biology of gliomas and the role of tyrosine
      kinase receptors and signal transduction pathways in tumor initiation and
      maintenance, such as the epidermal growth factor receptors, platelet-derived
      growth factor receptors, vascular endothelial growth factor receptors, and the
      Ras/Raf/mitogen-activated protein (MAP)-kinase and phosphatidylinositol-3 kinase
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways. Novel targeted drugs
      such as small molecular inhibitors of these receptors and signaling pathways are
      showing some activity in initial studies. As we learn more about these drugs and
      how to optimize their use as single agents and in combination with radiation,
      chemotherapy, and other targeted molecular agents, they will likely play an
      increasing role in the management of this devastating disease. This review
      summarizes the current results with targeted molecular agents in malignant
      gliomas and strategies under evaluation to increase their effectiveness.

PMID- 16464406
TI  - Diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated
      acquired polyneuropathy that may lead to disability. CIDP is characterized by an
      autoimmune attack against peripheral nervous system myelin, by cellular and
      humoral mechanisms. Early diagnosis and treatment may yield better functional
      recovery, probably by minimizing secondary axonal loss from a primary
      demyelinating insult. Intravenous immunoglobulin and plasmapheresis are
      considered standard-of-care therapy in CIDP, based on randomized, double-blinded,
      placebo-controlled evidence. Corticosteroids, despite less robust evidence, are
      also considered standard therapy for CIDP. Other nonstandard therapies may work
      in refractory patients. These include azathioprine, cyclophosphamide,
      cyclosporine A, etanercept, interferon-alpha 2a, mycophenolate mofetil, and
      tacrolimus. Emerging therapies include interferon-beta 1a, rituximab, and high
      dose cyclophosphamide without stem-cell rescue. Because most patients will
      require prolonged therapy, long-term side effects are important considerations.

PMID- 16464408
TI  - Treatment options for autonomic neuropathies.
AB  - Autonomic disorders may present in a varied fashion. Symptoms that may require
      treatment include orthostatic intolerance, gastrointestinal distress, sudomotor
      abnormalities, and urologic and sexual dysfunction. Realistic treatment goals
      should be outlined for patients, with the expectations that symptoms can be
      improved, but that the disease is unlikely to be cured and long-term therapy may
      be required. Orthostatic intolerance is usually treated by a combination of
      pharmacologic and nonpharmacologic therapies. Nonpharmacologic therapies include
      compression stockings, adequate fluid and salt intake, and lifestyle
      modifications. Polypharmacologic therapy is often the standard and can include a
      volume-expanding agent (such as fludrocortisone) and a sympathomimetic agent.
      This combination will improve symptoms dramatically in most patients. Treatment
      of gastrointestinal disorders should address the particular symptom involved:
      gastroparesis, constipation, or diarrhea. Treatment of sexual and urogenital
      dysfunction often requires a combination of pharmacologic intervention and
      lifestyle modifications for peak effectiveness. Patient education is the
      cornerstone of treatment in any of the autonomic disorders. Given enough
      education and motivation, many patients will be able to participate in their
      treatment, which will provide a feeling of empowerment and control over a disease
      that is often frustratingly resistant to treatment.

PMID- 16464407
TI  - Therapy for vasculitic neuropathies.
AB  - The term vasculitis refers to a pathologic condition defined by inflammatory cell
      infiltration and destruction of blood vessels. Systemic vasculitis is classified
      as primary (eg, polyarteritis nodosa, Churg-Strauss syndrome) or secondary, the
      latter associated with connective tissue disorders, infections, medications, and
      rarely, as a paraneoplastic phenomenon. Neuropathy is a common complication of
      systemic vasculitis and is related to ischemic nerve fiber damage with axon loss.
      Peripheral neuropathy may be the sole manifestation of vasculitis, a condition
      termed nonsystemic vasculitic neuropathy (NSVN). Treatment of vasculitic
      neuropathy requires long-term immunosuppressive therapies with potential side
      effects. The diagnosis of vasculitis should be established by tissue (preferably
      nerve) biopsy. High-dose prednisone is the standard platform therapy for patients
      with systemic and NSVN; for those with systemic vasculitis, at least 3 to 12
      months of treatment with cyclophosphamide (monthly intravenous pulse or daily
      oral therapy) is also necessary to sustain remission and allow successful
      prednisone tapering. The use of cyclophosphamide in patients with NSVN is
      controversial, but recent retrospective data suggest that those treated with
      prednisone and cyclophosphamide from the outset fare better than those initially
      treated only with prednisone. If prednisone is administered as monotherapy,
      cyclophosphamide should be added after several months if there is no improvement
      or relapse occurs with tapering of prednisone. Intravenous pulse and daily oral
      cyclophosphamide probably offer similar efficacy, although the risk of
      complications is greater with oral therapy. Azathioprine can be safely
      substituted for cyclophosphamide after 3 months without an increased relapse
      rate. Azathioprine, methotrexate, intravenous immune globulin, mycophenolate
      mofetil, plasma exchange, and rituximab can be offered to patients who are
      intolerant or have a contraindication to cyclophosphamide. However, efficacy is
      unproven for any of these therapies. Interferon-alpha, sometimes combined with
      plasma exchange, is used to treat vasculitis associated with hepatitis B
      infection. Some patients also may improve with corticosteroids. The
      classification of diabetic lumbosacral radiculoplexus neuropathy as a vasculitic
      disorder remains controversial. However, there is compelling pathological
      evidence that this condition represents a T-cell-mediated microvasculitis. Some
      patients treated with intravenous corticosteroids may have greater recovery and
      improved pain control.

PMID- 16464409
TI  - Central nervous system infections in the neurointensive care unit.
AB  - Central nervous system (CNS) infections are frequently encountered at the primary
      care level, in emergency rooms, medical wards, and intensive care units. Advances
      in immunization techniques and aggressive prevention campaigns have had an impact
      on the worldwide incidence of community-acquired meningitis, limiting this
      disease to the adult population. In general, a high index of suspicion is
      required for the diagnosis, but special attention should be given to the
      immunocompromised host and post-neurosurgical patient in whom the clinical
      presentation may be nonspecific. Once the diagnosis is made, broad-spectrum
      antimicrobials should be administered, followed by diagnostic testing, and
      targeted antibiotic therapy. Current guidelines for the treatment of meningitis
      are clinically effective but are not based on randomized, prospective, controlled
      trials. Despite current therapies, the morbidity of CNS infections is still
      devastating. Recent trials of the use of corticosteroids as coadjuvants of
      antibiotic therapy showed promising results and decrease in the morbidity
      associated with bacterial and tuberculous meningitis. Additional neuroprotective
      alternatives should be the focus of future research. Similarly, guidelines for
      the diagnosis and management of post-neurosurgical procedure meningitis and
      ventriculostomy-related infections are needed.

PMID- 16464411
TI  - Advances in treatment of acute ischemic stroke.
AB  - Stroke carries a severe toll in terms of loss of life and disability for patients
      and their families. Until 10 years ago, physicians, and in particular
      neurologists, had a conservative, nonaggresive approach to this devastating
      disease. The advent of thrombolytic therapy not only proved that acute ischemic
      stroke is treatable, but also that early reperfusion can dramatically change the
      outcome of acute stroke patients. As a result of these trials, intravenous (IV)
      tissue plasminogen activator (t-PA) has been approved for treatment of acute
      ischemic stroke within 3 hours after symptom onset in the United States, Canada,
      Australia, and the European Union. The near future is extremely promising.
      Imaging modalities, such as diffusion- and perfusion-weighted images, as well as
      CT perfusion and CT angiography, to better select patients for treatment are now
      routinely performed in most academic medical centers. Novel IV and intra-arterial
      (IA) agents have been developed and tested. Emerging therapies will soon be
      available to increase the therapeutic windows for thrombolysis both by better
      screening patients using MRI or CT and by new IV and IA treatments. Several
      multicenter controlled trials in both imaging-guided decisions and therapeutic
      agents are either completed or being performed. We review data on advancement in
      imaging and treatment of acute ischemic stroke, in particular focusing on
      pharmacologic and mechanical IA thrombolysis.

PMID- 16464410
TI  - Modern treatment options for intracerebral hemorrhage.
AB  - Spontaneous intracerebral hemorrhage (ICH) is a devastating neurological event
      with a 30-day mortality of approximately 40%. Recent research provides new
      insights into the pathophysiology of ICH-associated edema, with potential
      molecular and cellular targets for future therapy. Neuroimaging techniques such
      as gradient echo MRI are yielding insights into cerebral microbleeds and the
      microangiopathies associated with hypertension and cerebral amyloid angiopathy.
      Recent literature provides new medical treatment strategies for fever, acute
      hypertension, and perihematomal edema, and methods of reducing intracranial
      pressure. Two randomized controlled trials have provided crucial evidence
      regarding surgical and medical intervention for acute ICH intervention.
      Recombinant factor VIIa appears to lessen growth of ICH when administered within
      4 hours of ictus. Further study of potential efficacy and safety is underway in
      an international phase III trial. In addition, the Surgical Trial in
      Intracerebral Hemorrhage reported results from an international randomized trial
      of 1033 patients who did not show benefit for surgical evacuation of ICH,
      compared with medical therapy alone. Less invasive surgical methods for hematoma
      evacuation, studied previously over the past decade, continue to be investigated.

PMID- 16464412
TI  - Update in the treatment of traumatic brain injury.
AB  - This review focuses on recent advances in the treatment of traumatic brain injury
      (TBI) during 2004 and 2005. Injured brain is a very heterogeneous structure,
      significantly evolving over time. Implementation of multimodal neuromonitoring
      will certainly provide more insights into pathophysiology of TBI. More studies
      are needed to determine how to best incorporate these new parameters into
      effective management protocols. Based on current literature, corticosteroids
      should not be indicated for the treatment of TBI. Avoidance or immediate
      treatment of secondary insults remains a mainstream of clinical care for patients
      with TBI. It seems that the therapy should focus on control of intracranial
      hypertension, and values of cerebral perfusion pressure around 60 mm Hg appear to
      correlate with favorable outcome in most patients. Hypertonic saline may become a
      preferred osmotherapeutic agent in severely head-injured patients, especially
      those with refractory intracranial hypertension. Benefit and indications for
      performing a decompressive craniectomy remain to be determined. Overall,
      individualized treatment respecting actual status of a patient's intra- and
      extracranial homeostasis should be the key principle of our current therapeutic
      approach toward severely head-injured patients.

PMID- 16464419
TI  - [Checklists for authors, revisers and editors of medical journals].

PMID- 16464420
TI  - [The processes of manuscript evaluation and publication in Medicina Clinica. The
      editorial committee of Medicina Clinica].
AB  - The decision-making process includes a series of activities undertaken in
      biomedical journals from the moment a manuscript is received until it is accepted
      or rejected. Firstly, the manuscript is evaluated by the members of the Editorial
      Board, who analyze both its suitability for the journal and its scientific
      quality. After this initial evaluation, the article is evaluated by peer
      reviewers, an essential process to guarantee its scientific validity. Both the
      Editorial Board and the peer reviewers usually use checklists which are of
      enormous help in this task. Once the biomedical article has been accepted, the
      publication process is started, which in turn includes a series of steps,
      beginning with technical and medical review of the article's contents and ending
      with the article's publication in the journal. The present article provides a
      detailed description of the main technical and ethical issues involved in the
      processes of decision-making and publication of biomedical articles.

PMID- 16464421
TI  - [Developing guidelines for reporting healthcare research: scientific rationale
      and procedures].
AB  - Healthcare research is extremely important, with the clear potential to influence
      treatment and prevention of disease, possibly on a global scale. Yet deficiencies
      in how research studies are reported are both well-documented and widespread
      across all medical specialties, types of interventions and study designs.
      Although randomised trials have received the most attention in this regard,
      similar concerns have been expressed about reporting of other types of research
      including diagnostic and epidemiological studies. If a journal article describes
      in enough detail what was done at each stage of a study, readers will have enough
      information to allow them to decide on the merits of the results for themselves.
      From this simple idea comes the scientific rationale of developing guidelines on
      how to report research. We consider desirable attributes of such guidelines,
      emphasising the importance of being evidence-based where possible. We describe
      recommended processes to produce guidelines that have evolved over several years
      during the preparation of a sequence of reporting guidelines including CONSORT,
      QUOROM, STARD and STROBE.

PMID- 16464422
TI  - [Common and specific methodological features of checklists].
AB  - As medical aims, diagnosis, prognosis, intervention and prevention benefit from
      scientific method, although they have specific characteristics requiring distinct
      types of design and statistical analysis. The present article aims to provide
      definitions of the common and differential features of checklists for the main
      study designs. Distinctions are made between statistical inference and decision,
      systematic and random error, confirmation and exploration, prediction and
      intervention, observation and experimentation, and random allocation and random
      selection. In addition, the main tools available to researchers to control random
      and systematic errors are described. How all of these elements are contained in
      the main types of design is discussed. Importantly, checklists are not a measure
      of the quality of a study but rather represent minimum requirements that aim to
      improve the quality of scientific reports.

PMID- 16464423
TI  - [Randomized clinical trials (CONSORT)].
AB  - It has been repeatedly shown that the information supplied in publications of
      clinical trials is frequently insufficient or inaccurate and that some
      methodologic problems are associated with exaggerated estimates of the effect of
      healthcare interventions. To improve the quality of reports of clinical trials, a
      group of scientists and editors developed the CONSORT statement (Consolidated
      Standards of Reporting Trials), a 22-item checklist (plus flow diagram), that can
      be used by authors, editors, reviewers, and readers. After publication in 1996,
      CONSORT was adopted by several journals and editorial groups. In 1999, a second
      version was drawn up, which was published in 2001. This article presents the
      Spanish translation of the two elements integrating the revised CONSORT, the flow
      diagram and the 22-item checklist, and provides a short comment on each of them.
      Previous publications of the CONSORT statement and other useful resources such as
      examples of what are considered good communications may be obtained from the
      CONSORT web site (http://www.consort-statement.org).

PMID- 16464424
TI  - [The CONSORT statement for cluster randomised trials].
AB  - With the publication of the CONSORT statement there is now increased awareness of
      the need to adequately report the findings of randomised controlled trials. The
      CONSORT statement includes a checklist of items that should be addressed in the
      trial report. The original CONSORT statement was developed to ensure the
      appropriate reporting of parallel group randomised controlled trials in which
      individual participants are allocated to different intervention groups. In
      cluster randomised trials, however, groups of participants, rather than
      individuals, are randomly allocated to study groups. The process of allocating
      groups of participants raises additional reporting considerations and led to the
      publication of an extension to the CONSORT statement specifically for cluster
      randomised trials. In this paper we review the CONSORT extension to cluster
      randomised trials, outlining the special features of the cluster randomised trial
      which must be considered.

PMID- 16464425
TI  - [Meta-analyses (QUOROM)].
AB  - The increase in the number of published systematic reviews and meta-analyses over
      the last few years has highlighted the need to establish guidelines for their
      publication, in order to facilitate their interpretation and use. The Quality of
      Reporting of Meta-analyses Conference, which took place in 1996, resulted in the
      QUOROM statement, consisting of a checklist and flow diagram. The checklist is
      composed of 18 items to encourage authors to provide essential information to
      readers about the methods and results of the meta-analysis. The flow diagram of
      randomized clinical trials (RCT) helps to provide information about the number of
      RCTs identified, included and excluded in the meta-analysis and the reasons for
      excluding them. Both tools provide standards for improving the quality of
      reporting of meta-analyses to make them rigorous, useful and reliable.

PMID- 16464426
TI  - [Non-randomized evaluation studies (TREND)].
AB  - Nonrandomized intervention trials are needed when randomized clinical trials
      cannot be performed. To report the results from nonrandomized intervention
      studies transparently, the TREND (Transparent Reporting of Evaluations with
      Nonrandomized Designs) checklist should be used. This implies that nonrandomized
      studies should follow the remaining methodological tools usually employed in
      randomized trials and that the uncertainty introduced by the allocation mechanism
      should be explicitly reported and, if possible, quantified.

PMID- 16464427
TI  - [Observational studies in epidemiology (STROBE)].
AB  - Although there are many texts on the quality of epidemiological studies, little
      effort has been made to evaluate the publication of epidemiological studies and
      their results (the articles). Concern to improve the reporting of epidemiological
      studies prompted a working group to launch the STROBE (Strengthening the
      Reporting of observational studies in Epidemiology Statement). The STROBE
      checklist contains 22 items organized according to the Title and Abstract,
      Introduction, Methods, Results, and Discussion structure that can be used for the
      main epidemiological designs (cohort studies, case-control studies, and cross
      sectional studies). It is a checklist to improve the reporting quality of
      epidemiological studies (generally original articles) and, therefore, to evaluate
      the quality of this type of publication and facilitate critical reading.

PMID- 16464428
TI  - [Diagnostic (STARD) and prognostic (REMARK) studies].
AB  - Deficiencies in how research studies are reported are both well-documented and
      widespread across all medical specialties and study designs. Although randomised
      trials have received the most attention in this regard, similar concerns have
      been expressed about reporting of other types of research including diagnostic
      and epidemiological studies. If a journal article describes in enough detail what
      was done at each stage of a study, readers will have enough information to allow
      them to decide on the merits of the results for themselves. From this simple idea
      comes the scientific rationale of developing guidelines on how to report
      research. Recommended processes to produce reporting guidelines have evolved over
      several years during the preparation of a sequence of reporting guidelines
      starting with CONSORT and QUOROM in the 1990s. We describe initiatives to develop
      reporting guidelines for diagnostic accuracy studies (STARD) and tumour marker
      prognostic studies (REMARK).

PMID- 16464429
TI  - [Health-related quality of life instruments and other patient-reported outcomes].
AB  - In the last few years, many different instruments assessing health-related
      quality of life and the broader concept of Patient-Reported Outcomes (PRO) have
      been developed. Following the recommendations of the Scientific Advisory
      Committee of the Medical Outcomes Trust, the ePRO checklist provides a modular
      assessment for PRO instruments based on eight key attributes: conceptual and
      measurement model, reliability, validity, responsiveness, interpretability,
      respondent and administrative burden, alternative forms, and cross-cultural
      adaptation. Selected criteria describing each attribute in detail are also
      listed. The availability of explicit guidelines is expected to promote the
      development of better PRO measurement instruments.

PMID- 16464430
TI  - [Economic evaluation studies in health].
AB  - Clinical journals often publish economic evaluation studies of health
      technologies and programs. To improve the peer review process and, hence, the
      quality and validity of published studies, the British Medical Journal (BMJ)
      established publication guidelines for the publication of economic evaluations
      aimed at authors, reviewers and editors. The present article analyzes the
      opportunity of adopting the BMJ's or similar guidelines by Medicina Clinica and
      the probable effectiveness of this measure. The article concludes that although
      this initiative would probably improve the review process and the quality of the
      papers published, it might be worthwhile to review, up-date and adapt the BMJ
      guidelines to the Spanish context by means of a consensus-forming process.
      Finally, this article discusses the limitations of the peer review process in
      improving the quality and validity of economic evaluations and suggests some
      complementary measures, drawing on lessons and experiences from the field of
      clinical research.

PMID- 16464431
TI  - [Methodological recommendations of the Regulatory Agencies].
AB  - The suitability of new drugs for use in the general population in terms of risk
      and benefit is assessed by the health authorities through their drug agencies.
      These agencies regulate the entry of drugs on the market and their conditions for
      use according to strict criteria of quality, safety and efficacy. To preserve the
      principle of transparency, the requirements are previously published as
      guidelines, which are freely available on the Internet. All these guidelines have
      the following basic recommendations in common: (a) appropriate methodology for
      the objective, defined in detail a priori, (b) traceability, (c) verification of
      the appropriateness of the methodology applied, (d) justification of any
      deviation from the initial plan and (e) demonstration of the robustness of the
      results in distinct scenarios. Regulatory guidelines differ from other
      methodological references in their emphasis on the practical issues of the design
      and performance of studies, accepted methodological principles, and systems to
      ensure quality assurance in research. Although these requirements might not be
      universally applied to all types of research, the guidelines are freely available
      and are a good reference for the authorship, review and publication of clinical
      trials. The present article aims to review some of the guidelines that could be
      especially useful.

PMID- 16464432
TI  - Refinement of techniques for the propagation of Leishmania donovani in hamsters.
AB  - Improved animal models are urgently required for drug and vaccine development
      against visceral leishmaniasis. Here we report refinements to the hamster model
      of infection that reduce the severity of the disease as well as the number of
      animals required to maintain infection while improving parasite yields. A
      comparison between infection via the intracardiac and intraperitoneal routes
      showed that the less commonly used intraperitoneal route is the simpler and
      preferred method. The KAtex latex agglutination test for visceral leishmaniasis
      accurately detected Leishmania donovani antigen in hamster urine as early as 6
      weeks post-inoculation. With modification, this assay could be an important tool
      in the evaluation of experimental drugs and vaccines.

PMID- 16464433
TI  - Population structure of the malaria vector Anopheles funestus (Diptera:
      Culicidae) in Madagascar and Comoros.
AB  - Microsatellites were used as markers for a study of the population structure of
      Anopheles funestus on Madagascar and Comoros. Mosquitoes were collected in four
      different localities on Madagascar and one on Comoros. There was a significant
      genetic differentiation between all samples from Madagascar and that from Comoros
      (P<0.05). With respect to the Madagascar mosquito samples, it was found that
      there were no significant genetic differences between samples that were collected
      at the east coast, and in the highlands, respectively. By contrast, the west
      coast sample exhibited significant genetic differences (with regard to all
      Madagascar samples). The results are discussed with respect to population
      distribution and migration of A. funestus from mainland Africa and the islands
      east of the mainland.

PMID- 16464434
TI  - Purification of His-tagged hybrid phage antibody.

PMID- 16464435
TI  - Cyclic AMP-dependent functional forms of cyclic AMP receptor protein from Vibrio
      cholerae.
AB  - The cyclic AMP receptor protein (CRP) from Escherichia coli, involved in the
      transcriptional regulation of a number of genes and operons, works by binding to
      specific sites upstream of promoters. CRP also binds cyclic AMP (cAMP), and this
      binding, which causes conformational changes in CRP, is mandatory for its
      activity. A cAMP-dependent variation in the conformation as well as biological
      activity of E. coli CRP has been reported, with the cAMP-CRP complex formed at
      high cAMP concentrations resembling the uncomplexed apoprotein CRP. CRP from
      Vibrio cholerae, which plays an important role in the regulation of virulence
      gene expression, has a 95% sequence identity with the E. coli protein. We have
      purified and characterized V. cholerae CRP and studied its transcription
      activation properties as a function of increasing cAMP concentrations. A biphasic
      dependence on cAMP levels was observed, similar to that found for E. coli CRP.
      The implications of these results on regulation of cAMP-CRP dependent promoters
      in V. cholerae has been discussed.

PMID- 16464436
TI  - Cholesterol affects spectrin-phospholipid interactions in a manner different from
      changes resulting from alterations in membrane fluidity due to fatty acyl chain
      composition.
AB  - We previously showed that erythrocyte and brain spectrins bind phospholipid
      vesicles and monolayers prepared from phosphatidylethanolamine and
      phosphatidylserine and their mixtures with phosphatidylcholine (Review: A.F.
      Sikorski, B. Hanus-Lorenz, A. Jezierski, A. R. Dluzewski, Interaction of membrane
      skeletal proteins with membrane lipid domain, Acta Biochim. Polon. 47 (2000)
      565). Here, we show how changes in the fluidity of the phospholipid monolayer
      affect spectrin-phospholipid interaction. The presence of up to 10%-20%
      cholesterol in the PE/PC monolayer facilitates the penetration of the monolayer
      by both types of spectrin. For monolayers constructed from mixtures of PI/PC and
      cholesterol, the effect of spectrins was characterised by the presence of two
      maxima (at 5 and 30% cholesterol) of surface pressure for erythroid spectrin, and
      a single maximum (at 20% cholesterol) for brain spectrin. The binding assay
      results indicated a small but easily detectable decrease in the affinity of
      erythrocyte spectrin for FAT-liposomes prepared from a PE/PC mixture containing
      cholesterol, and a 2- to 5-fold increase in maximal binding capacity (B(max))
      depending on the cholesterol content. On the other hand, the results from
      experiments with a monolayer constructed from homogenous synthetic phospholipids
      indicated an increase in deltapi change with the increase in the fatty acyl chain
      length of the phospholipids used to prepare the monolayer. This was confirmed by
      the results of a pelleting experiment. Adding spectrins into the subphase of raft
      like monolayers constructed from DOPC, SM and cholesterol (1/1/1) induced an
      increase in surface pressure. The deltapi change values were, however, much
      smaller than those observed in the case of a natural PE/PC (6/4) monolayer. An
      increased binding capacity for spectrins of liposomes prepared from a "raft-like"
      mixture of lipids could also be concluded from the pelleting assay. In
      conclusion, we suggest that the effect of membrane lipid fluidity on spectrin
      phospholipid interactions is not simple but depends on how it is regulated, i.e.,
      by cholesterol content or by the chemical structure of the membrane lipids.

PMID- 16464437
TI  - Commensals upon us.
AB  - A battle to control and curtail bacterial infectious diseases is being waged in
      our hospitals and communities through antibiotic therapies and vaccines targeting
      specific species. But what effects do these interventions have on the
      epidemiology of infections caused by the organisms that are part of our natural
      microbial flora? Gram-positive and gram-negative bacteria appear as new disease
      agents from among commensal flora. These include vancomycin resistant enterococci
      (VRE), community-associated methicillin resistant Staphylococcus aureus (CA
      MRSA), non-vaccine invasive serotypes of Streptococcus pneumoniae, new strains of
      non-type b Haemophilus influenzae and multi-drug resistant Escherichia coli.
      These examples illustrate how clinical improvements and widespread use and misuse
      of antibiotics have pushed evolution, allowing normally non-pathogenic strains to
      become infectious disease threats to human health.

PMID- 16464438
TI  - Inhibition of TNFalpha-induced activation of nuclear factor kappaB by kava (Piper
      methysticum) derivatives.
AB  - The inducible transcription factor nuclear factor kappaB (NF-kappaB) plays a
      central role in the regulation of immune, inflammatory and carcinogenic
      responses. While normal activation of NF-kappaB is required for cell survival and
      immunity, its deregulated expression is a characteristic of inflammatory and
      infectious diseases. In this study, we investigated the molecular mechanisms
      induced by lactones and chalcones isolated from Fijian kava (Piper methysticum)
      used in traditional medicine against urinary tract infections and asthma. In
      order to understand underlying regulatory mechanisms, inhibition of both NF
      kappaB-driven reporter gene expression and TNFalpha-induced binding of NF-kappaB
      to a consensus response element was achieved at concentrations of 320 microM
      (flavokavain A), 175 microM (flavokavain B) and 870 microM (kavain and
      dihydrokavain). Moreover, kavain and flavokavains A and B treatment led to
      inhibition of both inhibitor of kappaB (IkappaB) degradation and subsequent
      translocation of p50 and p65 NF-kappaB subunits from the cytoplasm to the nucleus
      as shown by Western blot analysis. Additionally, kinase selectivity screening
      demonstrates that flavokavain A, but not kavain, nor flavokavain B, inhibits the
      IkappaB kinase (IKK) as well as PRAK (p38-regulated/activated kinase), MAPKAP-K3
      (MAPK-activated protein kinase 3), DYRK1A (dual-specificity tyrosine
      phosporylated and regulated kinase 1A) and Aurora B. Altogether, these results
      give a first insight into anti-inflammatory mechanisms triggered by traditionally
      used chemopreventive kava compounds.

PMID- 16464440
TI  - Model-generated lexical activity predicts graded ERP amplitudes in lexical
      decision.
AB  - Recent neurocognitive studies of visual word recognition provide information
      about neuronal networks correlated with processes involved in lexical access and
      their time course (e.g., [Holcomb, Ph.J., Grainger J. and O'Rourke, T. (2002). An
      Electrophysiological Study of the Effects of Orthographic Neighborhood Size on
      Printed Word Perception, J. of Cogn. Neurosci. 14 938-950; Binder, J.R.,
      McKiernan, K.A., Parsons, M.E., Westbury, C.F., Possing, E.T., Kaufman, J.N. and
      Buchanan, L. (2003). Neural Correlates of Lexical Access during Visual Word
      Recognition, J. Cogn. Neurosci. 15 372-393.]). These studies relate the
      orthographic neighborhood density of letter strings to the amount of global
      lexical activity in the brain, generated by a hypothetical mental lexicon as
      speculated in an early paper by [Jacobs, A.M. and Carr, T.H. (1995). Mind mappers
      and cognitive modelers: Toward cross-fertilization, Behav. Brain. Sci. 18 362
      363]. The present study uses model-generated stimuli theoretically eliciting
      graded global lexical activity and relates this activity to activation of lexical
      processing networks using event-related potentials (ERPs). The results from a
      lexical decision task provide evidence for an effect of lexicality around 350 ms
      post-stimulus and also a graded effect of global lexical activity for nonwords
      around 500 ms post-stimulus. The data are interpreted as reflecting two different
      decision processes: an identification process based on local lexical activity
      underlying the 'yes' response to words and a temporal deadline process underlying
      the 'no' response to nonwords based on global lexical activity.

PMID- 16464439
TI  - AM251, a selective antagonist of the CB1 receptor, inhibits the induction of long
      term potentiation and induces retrograde amnesia in rats.
AB  - Long-term potentiation (LTP) has a long history as putative mechanism of memory
      formation, specially in the hippocampus, a structure essential for memory
      formation. Endocannabinoids are one of the endogenous systems that modulate this
      plasticity event: the activation of hippocampal CB1 receptors may inhibit local
      GABA release. Here, we have studied both (1) the role of the selective CB1
      antagonist AM251 upon LTP induction in a hippocampal slice preparation, and (2)
      the effect of its intrahippocampal administration in the step-down inhibitory
      avoidance (IA) and the open field habituation tasks (OF). Standard extracellular
      electrophysiology techniques were used to record field excitatory postsynaptic
      potentials from the dendritic region of CA1 neurons in response to a high
      frequency stimulation of Schaffer's collaterals; a micropipette ejected 0.2
      microM of AM251 (in DMSO/PBS) 2 min before the stimulus: LTP was induced and
      lasted more than 30 min in the control, but not in the AM251-treated group.
      Immediately after training, either in IA (footshock, 0.5 mA) or OF, animals
      received a bilateral infusion of 0.55 or 5.5 ng/side of AM251 or its vehicle in
      the CA1 region, and test was performed 24 h later. AM251 has caused a
      significative decrease in the test step-down latency when compared to the control
      group, but no differences were detected in the OF task, including the number of
      crossings, i.e., there were no motor effects. The LTP supression could be caused
      by AM251 acting over GABAergic interneurons that modulate the LTP-bearing
      glutamatergic neurons. Endocanabinoids would then be the natural dis-inhibitors
      of local plasticity in the dorsal hippocampus, and the amnestic action of AM251
      would be due to a disruption of this endogenous modulatory system.

PMID- 16464441
TI  - Segregation and integration: roles played by caveolae and caveolins in the
      cardiovascular system.

PMID- 16464442
TI  - Caveolae and sarcoplasmic reticular coupling in smooth muscle cells of
      pressurised arteries: the relevance for Ca2+ oscillations and tone.
AB  - OBJECTIVE: A close association of caveolae and sarcoplasmic reticulum (SR) has
      been suggested to be important for contractile activation of smooth muscle. Here,
      we investigate the presence of such arrangements in pressurised resistance
      arteries and examine the influence of two agents purported to disrupt caveolae
      and/or SR conformations by different mechanisms of action. METHODS: Rat
      mesenteric small arteries (RMSA) were mounted on a pressure myograph and the
      functional (lumen diameter and Ca(2+) oscillations) and ultrastructural effects
      of the phosphatase inhibitor calyculin-A (cal-A), or the cholesterol binding
      agent methyl-beta-cyclodextrin (mbetacd), examined by light and electron
      microscopy. RESULTS: Smooth muscle cells of RMSA exhibited a prominent peripheral
      SR that often encircled individual caveolae. The peripheral SR on occasion was
      observed to make contact with centrally located SR allowing for a structural
      association of caveoale-SR-myofilaments. Cal-A maximally constricted RMSA and
      disrupted the regular SR-caveolae appearance such that concentrated swirls of SR
      not enveloping caveolae were evident. Mbetacd treatment, in contrast, inhibited
      agonist contractility and reduced the appearance of caveolae whilst peripheral SR
      apposition to the plasmalemma could still be observed. Treatment with either
      agent inhibited agonist-mediated smooth muscle Ca(2+) oscillations. CONCLUSION:
      We present data that supports a structural arrangement of caveolae and underlying
      peripheral SR in smooth muscle cells of pressurised resistance arteries that
      serves to regulate Ca(2+) oscillations and contractile activation.

PMID- 16464444
TI  - Analysis of Pax6 expression using a BAC transgene reveals the presence of a
      paired-less isoform of Pax6 in the eye and olfactory bulb.
AB  - Pax6, a member of the paired-family of transcription factors, exhibits restricted
      expression and essential functions in the developing eye, olfactory system,
      central nervous system, and pancreas. To understand Pax6 function, which
      critically depends on induction of proper expression levels during development,
      it is necessary to elucidate the molecular mechanisms governing Pax6
      transcription. Although previous studies using classic transgenic approaches have
      provided a wealth of information about the distribution and types of regulatory
      elements involved in Pax6 regulation, genetic studies in both humans and mice
      indicate that these enhancers alone are not sufficient for fully regulated Pax6
      expression. We report here our analysis of mice transgenic for a 160 kb mouse
      Pax6 BAC transgene, which was generated as a necessary first step towards testing
      the long-range control of Pax6 expression in vivo. We show that this BAC
      transgene replicates Pax6 expression in the eye. This is the first time that a
      reporter transgene has been expressed in a normal Pax6-like pattern in all of the
      tissues of the eye and defines an eye regulatory region within the Pax6
      downstream regulatory region (DRR). Second, we show that this BAC transgene
      contains all of the cis regulatory elements required for normal Pax6 expression
      within the developing embryo, except for within the diencephalon and olfactory
      bulb. Third, we show that this transgene is subject to Pax6 autoregulation.
      Lastly, we identify, for the first time in mammals, an isoform of the Pax6
      protein lacking the paired domain. This isoform is expressed in the developing
      olfactory bulb and eye. Over-expression of Pax6DeltaPD causes a microphthalmic
      phenotype in both Pax6(+/+) mice and Pax6(+/-) mice. These results demonstrate a
      role for Pax6DeltaPD in eye development, which appears to be different than that
      ascribed to either canonical Pax6 or Pax6(5a).

PMID- 16464445
TI  - Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial
      asthma and allergic respiratory diseases.
AB  - IgE molecules play a crucial role in allergic respiratory diseases and may cause
      chronic airway inflammation in asthma through activation of effector cells via
      high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII) IgE receptors. Since
      the discovery of IgE antibodies our understanding of the mechanisms of allergy
      has improved to such an extent that we can differentiate allergic/atopic from
      intrinsic respiratory diseases. Therapeutic anti-IgE antibodies, able to reduce
      free IgE levels and to block the binding of IgE to FcepsilonRI without
      crosslinking IgE and triggering degranulation of IgE-sensitized cells have been
      developed. This non-anaphylactogenic anti-IgE monoclonal antibody (omalizumab)
      binds IgE at the same site as these antibodies bind FcepsilonRI and FcepsilonRII.
      Consequently, omalizumab inhibits IgE effector functions by blocking IgE binding
      to high-affinity receptors on IgE effector cells and does not cause mast cell or
      basophil activation because it cannot bind to IgE on cell surfaces where the
      FcepsilonR1 receptor already masks the anti-IgE epitope. Studies in patients with
      atopic asthma showed that omalizumab decreases serum IgE levels and allergen
      induced bronchoconstriction during both the early and late-phase responses to
      inhaled allergen. In several clinical controlled trials omalizumab resulted
      effective in reducing asthma-related symptoms, decreasing corticosteroid use and
      improving quality of life of asthmatic patients. Recent studies show the benefits
      of omalizumab as add-on therapy in patients with severe persistent asthma who are
      inadequately controlled by optimal pharmacological therapy. The anti-IgE approach
      to asthma treatment has several advantages, including concomitant treatment of
      other IgE-mediated diseases such as allergic rhinitis, a favorable safety profile
      and a convenient dosing frequency.

PMID- 16464446
TI  - A closer look at chemokines and their role in asthmatic responses.
AB  - Inflammatory cell recruitment is a hallmark phenomenon of all inflammatory
      diseases, including allergic asthma. In allergy and asthma, recruitment of
      inflammatory cells such as T cells, dendritic cells, mast cells, eosinophils and
      neutrophils, is mediated via a number of chemokines and their receptors. Not only
      are chemokines involved in recruitment of these cells, they also play a role in
      activation and differentiation of inflammatory cells, among others, by
      selectively activating Th1 or Th2 cells or by effects on epithelial or
      endothelial cells. Binding of chemokines with their receptors has been
      demonstrated to be highly promiscuous and the subsequent activation pattern on
      effector cells is very heterogeneous, which has lead to confusion and has
      complicated research in this field. Nonetheless, chemokines and their receptors
      are important potential therapeutical targets in allergy and asthma because of
      their central role in cell recruitment and activation during inflammation.

PMID- 16464447
TI  - Extending the understanding of sensory neuropeptides.
AB  - The tachykinins substance P and neurokinin A are present in human airways, in
      sensory nerves and immune cells. Tachykinins can be recovered from the airways
      after inhalation of ozone, cigarette smoke or allergen. They interact in the
      airways with tachykinin NK1, NK2 and NK3 receptors to cause bronchoconstriction,
      plasma protein extravasation, and mucus secretion and to attract and activate
      immune cells. In preclinical studies they have been implicated in the
      pathophysiology of asthma and chronic obstructive pulmonary disease, including
      allergen- and cigarette smoke induced airway inflammation and bronchial
      hyperresponsiveness and mucus secretion. Dual NK1/NK2 or triple NK1/NK2/NK3
      tachykinin receptor antagonists offer therapeutic potential in airway diseases
      such as asthma and chronic obstructive pulmonary disease.

PMID- 16464448
TI  - Effects of mu-, delta- and kappa-opioid receptor agonists on methamphetamine
      induced self-injurious behavior in mice.
AB  - Opioid receptor agonists can differentially modify the behavioral effects of
      direct/indirect dopamine receptor agonists, such as methamphetamine, cocaine and
      apomorphine. However, the effects of opioid receptor agonists on high-dose
      methamphetamine-induced behavior have not yet been clarified. Therefore, the
      present study was undertaken to investigate the effects of mu (morphine)-, delta
      (SNC80)- and kappa (U50,488H)-opioid receptor agonists on methamphetamine-induced
      self-injurious behavior and locomotor activity in mice. Methamphetamine (20
      mg/kg) induced severe self-injurious behavior. In a combination test, some opioid
      receptor agonists significantly attenuated methamphetamine-induced self-injurious
      behavior, with potencies in the order morphine>buprenorphine (mu-opioid and kappa
      opioid receptor agonist/antagonist) >U50,488H, as maximum effects. These results
      suggest that the stimulation of mu- and kappa-opioid receptors plays an
      inhibitory role in high-dose methamphetamine-induced stereotypic self-injurious
      behavior in mice, without affecting locomotor activity.

PMID- 16464449
TI  - The transient receptor potential vanilloid 1: role in airway inflammation and
      disease.
AB  - The transient receptor potential vanilloid 1 (TRPV1) is an excitatory cation
      channel, rather selectively expressed in a subpopulation of nociceptive, primary
      sensory neurons that promote neurogenic inflammation via neuropeptide release.
      TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid
      derivatives, and is uniquely sensitive to vanilloid molecules, including
      capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G
      protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous
      chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide
      sensitize/activate TRPV1. In the airways, TRPV1 agonists cause cough,
      bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion.
      Patients with asthma and chronic obstructive pulmonary disease are more sensitive
      to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to
      respiratory symptoms caused by acidic media present in the airways during asthma
      exacerbation, gastroesophageal reflux induced asthma or in other conditions.
      TRPV1 antagonists may be useful in the treatment of these diseases.

PMID- 16464450
TI  - Reactive nitrogen species in the respiratory tract.
AB  - Endogenous Nitric Oxide (NO) plays a key role in the physiological regulation of
      airway functions. In response to various stimuli activated inflammatory cells
      (e.g., eosinophils and neutrophils) generate oxidants ("oxidative stress") which
      in conjunction with exaggerated enzymatic release of NO and augmented NO
      metabolites produce the formation of strong oxidizing reactive nitrogen species,
      such as peroxynitrite, in various airway diseases including asthma, chronic
      obstructive pulmonary diseases (COPD), cystic fibrosis and acute respiratory
      distress syndrome (ARDS). Reactive nitrogen species provoke amplification of
      inflammatory processes in the airways and lung parenchyma causing DNA damage,
      inhibition of mitochondrial respiration, protein dysfunction and cell damage
      ("nitrosative stress"). These effects alter respiratory homeostasis (such as
      bronchomotor tone and pulmonary surfactant activity) and the long-term
      persistence of "nitrosative stress" may contribute to the progressive
      deterioration of pulmonary functions leading to respiratory failure. Recent
      studies showing that protein nitration can be dynamic and reversible
      ("denitration mechanisms") open new horizons in the treatment of chronic
      respiratory diseases affected by the deleterious actions of "nitrosative stress".

PMID- 16464451
TI  - A conditionally immortal clonal stem cell line from human cortical
      neuroepithelium for the treatment of ischemic stroke.
AB  - Transplantation of neural stem cells into the brain is a novel approach to the
      treatment of chronic stroke disability. For clinical application, safety and
      efficacy of defined, stable cell lines produced under GMP conditions are
      required. To this end, a human neural stem cell line, CTX0E03, was derived from
      human somatic stem cells following genetic modification with a conditional
      immortalizing gene, c-mycER(TAM). This transgene generates a fusion protein that
      stimulates cell proliferation in the presence of a synthetic drug 4-hydroxy
      tamoxifen (4-OHT). The cell line is clonal, expands rapidly in culture (doubling
      time 50-60 h) and has a normal human karyotype (46 XY). In the absence of growth
      factors and 4-OHT, the cells undergo growth arrest and differentiate into neurons
      and astrocytes. Transplantation of CTX0E03 in a rat model of stroke (MCAo) caused
      statistically significant improvements in both sensorimotor function and gross
      motor asymmetry at 6-12 weeks post-grafting. In addition, cell migration and long
      term survival in vivo were not associated with significant cell proliferation.
      These data indicate that CTX0E03 has the appropriate biological and manufacturing
      characteristics necessary for development as a therapeutic cell line.

PMID- 16464452
TI  - Development and validation of a short form of the Chinese version of the State
      Anxiety Scale for Children.
AB  - BACKGROUND: There is a lack of a simplified instrument for use in busy clinical
      settings to measure and differentiate anxiety levels of children. OBJECTIVES: To
      develop a short form of the Chinese version of the State Anxiety Scale for
      Children (CSAS-C) and test psychometric properties of the new form. DESIGN: The
      study was divided into two phases with phase one aimed at developing a short form
      of the CSAS-C, while phase two aimed at testing psychometric properties of the
      new form. A test-retest, within-subjects design was employed. Children (7-12
      years of age) admitted for surgery in a day surgery unit during two consecutive
      years' summer holiday were invited to participate in the study. In phase one,
      selected participants (N=112) were asked to respond to the CSAS-C. In phase two,
      selected participants (N=82) were asked to respond to the short form of the CSAS
      C. RESULTS: Using exploratory factor analysis, a subset of 10 items, which was
      highly correlated with scores obtained from the full form (r=0.92) and, which had
      acceptable internal consistency (r=0.83) was developed. The psychometric
      properties of this short form have been empirically tested, showing adequate
      internal consistency reliability, good concurrent validity, and excellent
      construct validity. CONCLUSION: This study addresses a gap in the literature by
      developing a 10-item short form of the CSAS-C. Results indicate that this short
      form is an appropriate and objective assessment tool for measuring anxiety levels
      of Chinese children in a busy clinical setting where time constraints make
      unfeasible the use of the full form.

PMID- 16464453
TI  - Evaluation of the Morse Fall Scale: applicability in Chinese hospital
      populations.
AB  - BACKGROUND: Patient falls have been identified as a significant health problem in
      the general hospital patient population. The Morse Fall Scale (MFS) is an
      individualized criterion-referenced assessment tool designed for measuring the
      likelihood of patient falls in hospitals. Despite the scale has demonstrated high
      validity and reliability in the previous researches, this study is to provide
      additional validity tests to determine the applicability in the Chinese hospital
      population. OBJECTIVES: To examine the predictive power of the MFS to predict
      patient falls. To conduct reliability tests on internal consistency, item
      analysis, inter-rater and test-retest reliability. DESIGN: The study was a cross
      sectional study. SETTINGS: The medical and geriatric units of three
      rehabilitation hospitals in Hong Kong participated in the study. PARTICIPANTS: A
      convenience sample of 954 Chinese patients was recruited sequentially upon
      admission in the hospital ward units. They ranged in age from 17 to 100 years,
      with a mean of 70.2 years. METHODS: The patients were assessed for fall risk
      using the MFS on admission. Data was collected on the number of patients who fell
      rather than the number of falls. RESULTS: The scale had a sensitivity of 31% and
      a specificity of 83% when the cut-off point was determined at 45. The field test
      demonstrated excellent inter-rater reliability with an ICC value of 0.97 (95%CI
      0.94-0.98). Repeatability was high with an ICC of 0.98 (95% CI 0.98-0.99). The
      evaluation revealed a low Cronbach's alpha coefficient and a low to moderate item
      to-scale correlation. CONCLUSIONS: The evidence collected in this study has shown
      both the positive and negative aspects of using the MFS in assessing the fall
      risk of Chinese patients during rehabilitation. The discriminative validity and
      internal consistency reliability provide researchers and clinicians with a major
      step in further developing or modifying the scale.

PMID- 16464454
TI  - The influence of vessel wall elasticity and peripheral resistance on the carotid
      artery flow wave form: a CFD model compared to in vivo ultrasound measurements.
AB  - The Doppler flow wave form and its derived measures such as the pulsatility index
      provide clinically important tools for the investigation of arterial disease. The
      typical shape of Doppler flow wave forms is physiologically known to be largely
      determined by both peripheral resistance and elastic properties of the arterial
      wall. In the present study we systematically investigate the influence of both
      vessel wall elasticity and peripheral resistance on the flow wave form obtained
      from a CFD-simulation of blood flow in the carotid bifurcation. Numerical results
      are compared to in vivo ultrasound measurements. The in vivo measurement provides
      a realistic geometry, local elasticities and an input flow wave form for the
      numerical experiment. Numerical and experimental results are compared at three
      different sites in the carotid branches. Peripheral resistance has a profoundly
      decreasing effect on velocities in the external carotid artery. If elasticity is
      taken into account, the computed peak systolic velocities are considerably lower
      and a more realistic smoothing of the flow wave form is found. Together, the
      results indicate that only if both vessel wall elasticity and positive peripheral
      resistance are taken into account, experimentally obtained Doppler flow wave
      forms can be reproduced numerically.

PMID- 16464455
TI  - Determination of trans-resveratrol in grapes by pressurised liquid extraction and
      fast high-performance liquid chromatography.
AB  - A study has been made of the extraction of trans-resveratrol from grapes using
      pressurised liquids (PLE); for this, the first stage was to determine the
      stability of this compound during extractions at different temperatures (50, 100,
      150 degrees C), with quantitative recoveries being obtained up to 150 degrees C.
      By employing solid-phase extraction (SPE) it was possible to retain this compound
      and separate it from other interfering substances present in the grape. The
      method developed comprises a sequential extraction of the sample adsorbed (0.5g)
      on a polystyrene-divinylbenzene based sorbent in the extraction chamber, first
      with water at 40 degrees C and 40atm of pressure (three cycles of 5min), and then
      with methanol at 150 degrees C and 40atm (three cycles of 5min). The trans
      resveratrol content of the methanolic extract is determined by means of liquid
      chromatography. A rapid (5min) chromatographic method employing a monolithic
      column, with fluorescence detection, has been developed; for this, the conditions
      for detection of the compound were optimised (excitation at 310nm and emission at
      403nm). The analytical parameters of the method of chromatographic analysis
      developed have been calculated: linear range (0.11-2.75mg/L), detection limit
      (0.003mg/L), quantification limit (0.004mg/L). Using this method, three varieties
      of grape have been analysed and the concentration of trans-resveratrol in these
      has been determined.

PMID- 16464456
TI  - A generic method for the determination of acrylamide in thermally processed
      foods.
AB  - A generic sample preparation method for the determination of acrylamide in foods
      was developed. The method entails extraction with methanol, purification with
      Carrez I and II solutions, evaporation and solvent change to water, and cleanup
      with Oasis HLB solid-phase extraction (SPE) cartridge. The final extract was
      analyzed by liquid chromatography-mass spectrometry (LC-MS) for quantitation. The
      chromatographic separation was performed on ODS-3 column using the isocratic
      mixture of 0.01 mM acetic acid in 0.2% aqueous solution of formic acid at a flow
      rate of 0.6 ml/min at 25 degrees C. The recoveries of acrylamide from potato
      chips, biscuits and coffee ranged between 92.8 and 101.5% with relative standard
      deviations of 4.1% or less. The limit of detection (LOD) and the limit of
      quantitation (LOQ) were 2 ng/g and 6 ng/g in the basis of signal to noise ratios
      of 3:1 and 9:1, respectively.

PMID- 16464457
TI  - Prediction of the Lee retention indices of polycyclic aromatic hydrocarbons by
      artificial neural network.
AB  - A quantitative structure retention relationship technique using an artificial
      neural network (ANN) has been used for the prediction of the Lee retention
      indices for PAHs on SE-52 and DB-5 stationary phases. The selected descriptors
      that appear in the ANN model are the boiling point, molecular weight,
      connectivity index and the Schabron molecular size descriptor. The network was
      trained and optimized using a training and validation data sets. For the
      evaluation of the predictive power of the ANN, the optimized network was used to
      predict the temperature-programmed Lee retention indices of two unseen testing
      data sets. The results obtained showed that the mean of relative errors and the
      correlation coefficients between the calculated ANN and the experimental values
      of Lee retention indices for the validation and two testing sets are 1.42% and
      0.9460 on SE-52; 1.32% and 0.9381; 1.43% and 0.8939 on DB-5 stationary phases,
      respectively. These values are in good agreement with the relative error obtained
      by experiment.

PMID- 16464458
TI  - Study of conical columns with 10 degrees opening angle for preparative liquid
      chromatography.
AB  - The efficiency and sample capacity of conical liquid chromatographic columns with
      10 degrees opening angle were studied at different ratio of cross section areas
      of inlet to outlet (A(in)/A(out)) and column dimension. As the A(in)/A(out) ratio
      changed from 4 to 2.25, the reduced plate height (h) was reduced and the h value
      decreased 12% when the column dimension was scaled up proportionally because of
      relatively smaller dead volume on both end of the column. Compared to cylindrical
      columns having corresponding lengths and volumes, the conical columns with 10
      degrees opening angle were superior in column efficiency, resolution and the
      maximum peak concentration at column outlet; the loadability of conical column
      was improved 30-40% on injection volume and 50-60% on sample mass, respectively,
      over cylindrical columns.

PMID- 16464459
TI  - Simultaneous determination of bioactive flavone derivatives in Chinese herb
      extraction by capillary electrophoresis used different electrolyte systems-
      borate and ionic liquids.
AB  - In this paper, novel capillary electrophoresis (CE) methods, which used ionic
      liquids (1-ethyl-3-methylimidazoium tetrafluoroborate, 1-butyl-3-methylimidazoium
      tetrafluoroborate), were established to separate and determine some bioactive
      flavone derivatives in Chinese herb Seriphidium santolinum (Schrenk) Poljak. In
      order to investigate the traits of ionic liquids in CE, borate was also used as
      electrolyte to compare with. And the excellence of CE, which used ionic liquids
      as main running electrolyte and beta-cyclodextrin (beta-CD) as modifier, was
      illuminated as well. As a result of the study, the difference of ionic liquids
      and borate in CE was discussed and the advantage of CE, which used ionic liquids
      as electrolytes for separation, was shown. The analysis was obtained within short
      time (5-6 min). From the result, it was found that the system, which used ionic
      liquids, was robust because the joule heating was small. The method of CE, which
      used ionic liquids, has lower detection limits (0.137-0.642 microg/mL) than that
      of borate (0.762-1.036 microg/mL). And the CE, which used ionic liquids method,
      has lower limit of linear range (1.100-2.656 microg/mL), while that of CE, which
      used borate method, was 2.188-5.313 microg/mL.

PMID- 16464460
TI  - Improving sensitivity in simultaneous determination of copper carboxylates by
      nonaqueous capillary electrophoresis.
AB  - A new method of nonaqueous capillary electrophoresis (NACE) with UV
      spectrophotometric detection was developed and optimized for the simultaneous
      determination of seven carboxylates (trans-1,2-diaminocyclohexane-N,N,N',N'
      tetraacetic acid (CDTA), diethylenetriaminepentaacetic acid (DTPA),
      ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediamine-N,N',N'
      triacetic acid (HEDTA), nitrilotriacetic acid (NTA), 1,3-diaminopropane-N,N,N',N'
      tetraacetic acid (PDTA) and triethylenetetraaminehexaacetic acid (TTHA)) as
      copper complexes. The method development was carried out by using a fused silica
      capillary. Background electrolyte (BGE) was optimized and the best separation
      achieved by using 30mmolL(-1) potassium bromide in N-methylformamide (NMF) at
      apparent pH (pH(app)) 10.2. A voltage of +30kV and direct UV detection at 280nm
      were used in all measurements. Large-volume sample stacking using the
      electroosmotic flow pump (LVSEP) was tested in addition to basic capillary
      electrophoresis (CE) and observed to improve the separation of the analyte zones
      in the capillary. All the peaks in the electropherograms were properly separated,
      the calibration plots gave excellent correlation coefficients (R(2)>or=0.994) and
      all seven copper carboxylate complexes were detected in less than 20min using
      both the basic measurements and the large-volume sample stacking method. The new
      NACE method was tested with lake water and proved to be reliable.

PMID- 16464461
TI  - New chiral stationary phase with macrocyclic glycopeptide antibiotic eremomycin
      chemically bonded to silica.
AB  - A new chiral stationary phase (CSP) was prepared by attachment of macrocyclic
      glycopeptide antibiotic eremomycin to the epoxy-activated silica under mild
      conditions. In contrast to CSP with immobilized vancomycin, which is a close
      structural analogue of eremomycin, the prepared CSP reveals high
      enantioselectivity for separation of amino acids enantiomers. It was demonstrated
      by the example of ristocetin A CSP that method of the immobilization of
      macrocyclic glycopeptide antibiotics affects remarkably the resulting
      enantioselectivity.

PMID- 16464462
TI  - Determination of 2,4,6-trichloroanisole and 2,4,6-tribromoanisole on ng L-1 to
      pgL-1 levels in wine by solid-phase microextraction and gas chromatography-high
      resolution mass spectrometry.
AB  - A gas chromatography-high-resolution mass spectrometry (GC-HRMS) method using
      solid-phase microextraction (SPME) for the determination of 2,4,6
      trichloroanisole (TCA) and 2,4,6-tribromoanisole (TBA) in wine at low ng L(-1)
      levels was developed. A robust SPME method was developed by optimizing several
      different parameters, including type of fiber, salt addition, sample volume,
      extraction and desorption time. The quantification limit for TCA and TBA in wine
      was lowered substantially using GC-HRMS in combination with the optimized SPME
      method and allowed the detection of low analyte concentrations (ng L(-1)) with
      good accuracy. Limits of quantification for red wine of 0.3 ng L(-1) for TCA and
      0.2 ng L(-1) for TBA with gas chromatography-negative chemical ionization mass
      spectrometry and 0.03 ng L(-1) for TCA and TBA were achieved using GC-HRMS. The
      method was applied to 30 wines of which 4 wines were sensorically qualified as
      cork defected. TCA was found in three of these wines with concentrations in the
      range 2-25 ng L(-1). TBA was not detected in any of the samples.

PMID- 16464463
TI  - Influence of solvents on the conformational order of C18 alkyl modified silica
      gels.
AB  - The influence of solvents on the conformational order of C(18) alkyl modified
      silica gels is studied by means of variable temperature FTIR spectroscopy.
      Symmetric and anti-symmetric CH(2) stretching modes were utilized for getting
      qualitative information about the changes in alkyl chain conformational order as
      a function of both protonated and perdeuterated solvents. It was found that
      interaction between the C(18) alkyl modified silica gels and the mobile phase
      results in pronounced changes of the alkyl chain conformational order.
      Furthermore, it was observed that some perdeuterated solvents exhibit isotope
      effects, which again is reflected by a different alkyl chain conformational order
      as compared to the corresponding stationary phases with protonated solvents.

PMID- 16464464
TI  - Pro-nominal reference skills of second and fourth grade children with language
      impairment.
AB  - Pro-nominal referencing was evaluated in a sample of 569 children comprising four
      diagnostic subgroups: typical language (TL), specific language impairment (SLI),
      nonspecific language impairment (NLI), and typical language with low nonverbal IQ
      (LNIQ). Participants generated oral narratives in second grade and again in
      fourth grade. The narratives of the females in the TL group included a
      significantly higher rate of pro-nominal references than the narratives of both
      the males in the TL group and the females in the NLI group. A higher percentage
      of complete pro-nominal references was found in the TL group compared to the SLI
      group. These findings suggest that pro-nominal referencing measures are not
      sensitive enough to differentiate school-aged children with typical language
      development from those with language impairment. LEARNING OUTCOMES: The reader
      will: (1) become familiar with narrative language measures and (2) learn how
      groups of children with varying language and cognitive profiles perform on
      measures of referential cohesion.

PMID- 16464465
TI  - A new clinically relevant approach to expand myelin specific T cells.
AB  - Human self-reactive T cells are potentially involved in many autoimmune diseases.
      Although ex vivo detection of self-reactive T cells is possible, exhaustive
      functional characterization of these cells is impeded by their low frequency. In
      vitro expansion of antigen (Ag) specific T cells is typically achieved by using
      autologous (fresh or frozen) irradiated peripheral blood mononuclear cells
      (PBMCs), EBV-immortalized B cells or dendritic cells in the presence of Ag. These
      approaches require a large blood volume. We explored a method successfully
      applied for tumor specific T cells using in vitro expanded autologous B cells.
      PBMCs were stimulated with irradiated CD40L-expressing fibroblasts and IL-4,
      resulting in an enriched population of B cell that expressed high levels of MHC
      and co-stimulatory molecules, essential hallmarks of antigen presenting cells
      (APCs). Expanded B cells were loaded with Ag, irradiated and then used as APCs to
      stimulate T cells. The specificity of T cell lines was assessed by comparing
      their proliferation and IFN-gamma secretion when cultured with antigen-loaded B
      cells vs. unloaded B cells. T cell lines exhibiting antigen-specific
      proliferation and/or IFN-gamma secretion were expanded. Using this method, MBP
      and MOG specific CD4(+) and CD8(+) T cell lines were obtained from multiple
      donors in comparable numbers to those obtained using the traditional approach
      (i.e. fresh PBMCs as APCs) and were kept in culture for many weeks. We have shown
      that myelin specific CD4(+) and CD8(+) T cells can be expanded from a relatively
      small volume of blood (50-100 ml) from multiple donors using expanded B cells as
      APCs.

PMID- 16464466
TI  - A novel-type substrate-selectivity filter and ER-exit determinants in the UapA
      purine transporter.
AB  - We present a functional analysis of the last alpha-helical transmembrane segment
      (TMS12) of UapA, a uric acid-xanthine/H+ symporter in Aspergillus nidulans and
      member of the nucleobase-ascorbate transporter (NAT) family. First, we performed
      a systematic mutational analysis of residue F528, located in the middle of TMS12,
      which was known to be critical for UapA specificity. Substitution of F528 with
      non-aromatic amino acid residues (Ala, Thr, Ser, Gln, Asn) did not affect
      significantly the kinetics of UapA for its physiological substrates, but allowed
      high-capacity transport of several novel purines and pyrimidines. Allele-specific
      combinations of F528 substitutions with mutations in Q408, a residue involved in
      purine binding, led to an array of UapA molecules with different kinetic and
      specificity profiles. We propose that F528 plays the role of a novel-type
      selectivity filter, which, in conjunction with a distinct purine-binding site,
      control UapA-mediated substrate translocation. We further studied the role of
      TMS12 by analysing the effect of its precise deletion and chimeric molecules in
      which TMS12 was substituted with analogous domains from other NATs. The presence
      of any of the TMS12 tested was necessary for ER-exit while their specific amino
      acid composition affected the kinetics of chimeras.

PMID- 16464467
TI  - An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner
      ear and binds to harmonin (USH1C).
AB  - The driving forces for the regulation of cell morphology are the Rho family
      GTPases that coordinate the assembly of the actin cytoskeleton. This dynamic
      feature is a result of tight coupling between the cytoskeleton and signal
      transduction and is facilitated by actin-binding proteins (ABPs). Mutations in
      the actin bundling and PDZ domain-containing protein harmonin are the causes of
      Usher syndrome type 1C (USH1C), a syndrome of congenital deafness and progressive
      blindness, as well as certain forms of non-syndromic deafness. Here, we have used
      the yeast two-hybrid assay to isolate molecular partners of harmonin and
      identified DOCK4, an unconventional guanine exchange factor for the Rho family of
      guanosine triphosphatases (Rho GEF GTPases), as a protein interacting with
      harmonin. Detailed molecular analysis revealed that a novel DOCK4 isoform (DOCK4
      Ex49) is expressed in the brain, eye and inner ear tissues. We have further
      provided evidence that the DOCK4-Ex49 binds to nucleotide free Rac as effectively
      as DOCK2 and DOCK4 and it is a potent Rac activator. By immunostaining using a
      peptide antibody specific to DOCK4-Ex49, we showed its localization in the inner
      ear within the hair bundles along the stereocilia (SC). Together, our data
      indicate a possible Rac-DOCK4-ABP harmonin-activated signaling pathway in
      regulating actin cytoskeleton organization in stereocilia.

PMID- 16464468
TI  - Portal and systemic endotoxemia in abdominal operations: the significance of
      acute abdomen.
AB  - Little evidence is available for the implication of bacterial translocation in
      cases of acute abdomen. Intraoperative endotoxemia in both portal and systemic
      circulation was studied in 20 surgical patients with acute abdomen and in 36
      controls undergoing elective abdominal surgery. Blood was sampled simultaneously
      from a mesenteric vein immediately after opening the peritoneum and from a
      peripheral vein. Endotoxin was measured by a colorimetric Limulus amebocyte
      lysate assay and malondialdehyde (MDA) was measured by the thiobarbiturate assay
      and passage through a high-performance liquid chromatography (HPLC) system as a
      marker of the oxidative status. LPS concentrations (mean +/- SE) in portal vein
      blood from patients with acute abdomen was 5.69 +/- 1.58 and from patients with
      chronic diseases 1.05 +/- 0.07 EU/ml (P < 0.0001). Respective values for the
      systemic circulation were 4.98 +/- 1.47 and 1.36 +/- 0.31 EU/ml (P < 0.0001).
      Concentrations of MDA (mean +/- SE) in portal vein blood from patients with acute
      abdomen was 11.16 +/- 4.00 and from patients with chronic diseases was 10.56 +/-
      2.39 mum (P NS). Positive correlations were observed between endotoxin and MDA in
      both portal and systemic circulation. These results indicate increased levels of
      endotoxin in acute abdominal conditions pointing to the gut as the site of origin
      of the bacterial products.

PMID- 16464469
TI  - Expression of anti-apoptotic protein, Bcl-2, in liver regeneration after a
      partial hepatectomy.
AB  - BACKGROUND: Although Bcl-2 is well known to have anti-apoptotic activities in
      vitro and in vivo, the role of Bcl-2 relating to liver regeneration remains
      controversial. The aim of this study was to document the effect of Bcl-2
      expression on liver regeneration in rats undergoing a partial hepatectomy.
      MATERIAL AND METHODS: Adult male Wistar rats (n = 4/group) at 72 h before
      undergoing a 70% partial hepatectomy (PH) were administered 1 x 10(9) plaque
      forming units of adenovirus vector encoding either human Bcl-2 (group 1) or LacZ
      (group 2) intravenously and were sacrificed at 0, 12 h, and at 1, 2, 3, 7, 14,
      and 21 days postoperatively. In group 3, normal saline was injected instead of
      adenovirus vector. Liver regeneration was monitored by measuring the restituted
      liver mass and proliferating cell nuclear antigen (PCNA) immunostaining. The
      incidence of apoptosis in the liver was analyzed by the immunohistochemical
      detection of single-stranded DNA at 14 and 21 days postoperatively. RESULTS: The
      restituted liver mass showed significantly higher values in group 1 (26.1 +/-
      7.2%) than in group 2 (14.7 +/- 6.8%) and 3 (13.6 +/- 5.0%) at 1 day after PH (P
      < 0.05). The PCNA labeling index was significantly higher in group 1 (47.2 +/-
      9.9%) than in groups 2 (19.0 +/- 7.8%) and 3 (19.2 +/- 15.2%) at 1 day after a
      partial hepatectomy (P < 0.05). The hepatocyte growth factor (HGF) mRNA
      expression was significantly lower in group 1 than in group 2 at 12 h after PH (P
      < 0.05). The number of single-stranded DNA-positive cells decreased significantly
      more in group 1 (5.67 +/- 1.53 positive cells/10 fields per tissue) than those in
      group 2 (18.33 +/- 7.57 positive cells/10 fields per tissue) at 14 days after PH.
      CONCLUSIONS: These results thus indicated that an overexpression of anti
      apoptotic protein Bcl-2 does not necessarily have an anti-apoptotic effect on
      liver regeneration but appears to have a pro-proliferative effect in the early
      phase of liver regeneration.

PMID- 16464470
TI  - Controlled study of Inline radiofrequency coagulation-assisted partial
      nephrectomy in sheep.
AB  - BACKGROUND: Primary or secondary tumors of kidney often are managed by partial
      nephrectomy. Intraoperative blood loss can be significant. Laparoscopic partial
      nephrectomy may be even more challenging. We developed the Inline radiofrequency
      coagulation (ILRFA) probe for liver surgery. It uses radiofrequency energy to
      make a linear coagulative plane and considerably reduces bleeding during
      parenchymal transection. In this stud,y we tested the efficiency of ILRFA in
      ovine kidney. METHOD: Seven sheep were used in this study. Under general
      anesthetic, a laparotomy was performed in each sheep. The first two sheep were
      used as pilot experiments. Five partial nephrectomies were made in the remaining
      five sheep using ILRFA. As a control, a matching partial nephrectomy was made in
      each sheep using diathermy and sutures. Blood loss was measured by determining
      the difference in the weights of dry sponges and blood stained sponges after
      resection. A paired t test was used to compare the bleeding between the control
      and the ILRFA technique. RESULTS: The mean blood loss using ILRFA was 33.14 g (SD
      17) and 123.43 g (SD 72) in the control group. The bleeding was significantly
      reduced in the ILRFA group, with a P value of 0.0056. The time taken for applying
      the ILRFA was 3-4 min. CONCLUSION: We have achieved partial nephrectomy in ovine
      kidney using radiofrequency energy with significantly reduced blood loss.

PMID- 16464471
TI  - Biliary lipid output in the early stage of acute liver failure induced by 90%
      hepatectomy in the rat.
AB  - BACKGROUND: Differences in biliary lipid output were compared in rats after 70%
      or 90% hepatectomy (Hx) to evaluate a possible index of the early stage of acute
      liver failure. METHODS: Male Sprague-Dawley (SD) rats weighing 300 to 350 g were
      randomly divided into two groups for 70% Hx or 90% Hx, and animals were
      sacrificed at 0, 6, 24, and 48 h after Hx. Before sacrifice, a polyethylene tube
      was cannulated into the bile duct and bile was collected for 1 h. Outputs of
      total bile acids, phospholipid, and total cholesterol in serum and bile were
      determined. Biliary total cholesterol, bile acid concentrations, and bile acid
      component levels were determined using gas liquid chromatography. Hepatic
      microsomal cholesterol 7alpha-hydroxylase and sterol 12alpha-hydroxylase
      activities were also determined using high performance liquid chromatography.
      RESULTS: The 3-day survival rate after 90% Hx was 50%. In the 90% Hx group, the
      serum total bile acid concentration at each point was significantly higher than
      it was in the 70% Hx group. The bile flow rate and biliary outputs of
      cholesterol, phospholipid, and bile acids were significantly lower at 6 h after
      90% Hx than after 70% Hx. Among bile acid species, cholic and chenodeoxycholic
      acid outputs into bile were significantly less at 6 h after 90% Hx. The
      activities of cholesterol 7alpha-hydroxylase and sterol 12alpha-hydroxylase were
      decreased after 90% Hx. CONCLUSIONS: Our results suggest that determinations of
      the bile flow rate and biliary lipid outputs are supposed to be useful for early
      detection of hepatic failure after extensive hepatectomy.

PMID- 16464472
TI  - Antioxidant role of Umbelliferone in STZ-diabetic rats.
AB  - The objective of the study was to investigate the role of Umbelliferone (UMB) on
      lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver
      of streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar
      strain, weighing 180-200 g, were induced diabetes by administration of STZ (40
      mg/kg b.wt.) intraperitoneally. The normal and diabetic rats were treated with
      UMB (30 mg/kg b.wt.) dissolved in 10% dimethyl sulfoxide (DMSO) for 45 days.
      Diabetic rats had an elevation in the levels of lipid peroxidation markers
      (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and
      conjugated dienes (CD)), and a reduction in nonenzymic antioxidants (vitamin C
      and reduced glutathione (GSH) except vitamin E in the plasma and liver, and
      enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPx) in the liver. Decreased level of beta-carotene and increased
      level of ceruloplasmin (Cp) were observed in the plasma of diabetic rats.
      Treatment with UMB and glibenclamide brought back lipid peroxidation markers,
      nonenzymic and enzymic antioxidants to near normalcy. Since UMB treatment
      decreases lipid peroxidation markers and enhances antioxidants' status it can be
      considered as a potent antioxidant.

PMID- 16464473
TI  - Purification and characterization of neuropathy target esterase (NTE) from rat
      brain.
AB  - Neuropathy target esterase (NTE) is an integral membrane protein in vertebrate
      neurons and a member of a novel family of putative serine hydrolases. Neuropathic
      organophosphates react covalently with the active site serine residue of NTE,
      causing degeneration of long axons in spinal cord and peripheral nerves which
      becomes clinically evident 1-3 weeks after exposure to OPs, hence termed as
      organophosphate induced delayed neuropathy. The present study reports the
      isolation and characterization of NTE protein from rat brain. Rat brain
      microsomes were solubilized with phospholipase A2 and they were fractionated by
      gel filtration chromatography in S-300 column. The sample was eluted in buffer
      containing polyoxyethylene W1 detergent, which yielded an active fraction of 200
      kDa. The most enriched NTE active fraction was further purified by 3-9'
      mercaptononylthio-1,1,1-trifluoropropan-2-one bound to sepharose CL4B. The SDS
      PAGE confirmed the 155-kDa protein as the most likely candidate for NTE. Database
      searching of rat N-terminal protein revealed homology with variety of
      polypeptides from different organisms and suggested that NTE protein has function
      beyond the nervous system and mediates a biochemical reaction highly conserved
      through evolution.

PMID- 16464475
TI  - Effect of a high protein diet on glucose tolerance in the rat model.
AB  - The purpose of this study was to determine the effects of a high protein diet on
      glucose tolerance. Nine Sprague Dawley rats received a high protein (HP) diet
      (65% protein, 35% fat) and eight rats consumed a standard chow (SC) diet over
      eight weeks. Oral glucose tolerance tests (OGTT) were performed at the end of the
      third and the seventh week. The diet did not effect glucose tolerance in the
      first (SC=10357+/-294 mg/dl/120 min; HP=9846+/-300 mg/dl/120 min) or the second
      OGTT (SC=10134+/-395 mg/dl/120 min; HP=10721+/-438 mg/dl/120 min) as reflected by
      the area under the glucose concentration curve. Similarly, the area under the
      insulin concentration curve was not effected by the high protein diet during the
      first (SC=49.21+/-8.46 ng/ml/120 min; HP=41.75+/-10.54 ng/ml/120 min) or the
      second OGTT (SC=96.63+/-13.68 ng/ml/120 min; HP=92.77+/-17.44 ng/ml/120 min). The
      high protein diet group experienced a delayed glucose response for the first
      (SC=30 min at 112+/-7 mg/dl; HP=60 min at 101+/-5 mg/dl) and second OGTT (SC=15
      min at 117+/-5 mg/dl; HP=60 min at 95+/-7 mg/dl). Body mass increased to the same
      extent in each diet group from the initial to final weighing (SC=159+/-2 g to
      254+/-7 g; HP=157+/-2 g to 242+/-7 g). Despite a delay in peak glucose response,
      these findings suggest that glucose tolerance and body mass were neither
      adversely nor positively affected by a high protein diet.

PMID- 16464474
TI  - Lipoteichoic acid induces prostaglandin E(2) release and cyclooxygenase-2
      synthesis in rat cortical neuronal cells: involvement of PKCepsilon and ERK
      activation.
AB  - Inflammatory processes occur in the central nervous system (CNS) through
      mechanisms that differ from other inflammation, and with distinct cellular
      effects. Neuronal injury in bacterial meningitis is not a monocausal event, but
      is mediated by several factors. One is possible direct toxicity of bacterial
      compounds. Lipoteichoic acid (LTA) is a cell wall component unique to Gram
      positive bacteria. In a previous report, LTA could interact with CD14 to induce
      NF-kappaB activation, which is involved in transcriptional regulation of adhesion
      molecules, enzymes and cytokines. Although there are many aspects to
      neuroinflammation, the pathways involving the cyclooxygenase (COX)-2 and
      subsequent generation of prostaglandin clearly play a role. LTA has been shown to
      stimulate inflammatory responses in a number of in vivo and in vitro experimental
      models. However, little was known about the molecular mechanisms of LTA
      implicated in inflammatory responses in neurons. In this study, we characterized
      the mechanisms underlying signaling transduction in rat cortical neuronal cells
      challenged by LTA. Here, we first showed that in rat cortical neuronal cells, LTA
      might activate protein tyrosine kinase (PTK), phosphatidylcholine-specific
      phospholipase C (PC-PLC), and phosphatidylinositol-specific phospholipase C (PI
      PLC) to induce protein kinase Cepsilon activation, which in turn induces
      extracellular signal-regulated kinase (ERK) activation, finally inducing PGE(2)
      release and COX-2 synthesis.

PMID- 16464476
TI  - Hypocholesterolemic action of pre-germinated brown rice in hepatoma-bearing rats.
AB  - The effect of pre-germinated brown rice (PGBR) on cholesterol metabolism was
      studied in Donryu rats subcutaneously implanted with the ascites hepatoma cell
      line AH109A and compared with that of white rice (WR). The effect of brown rice
      (BR), the source of PGBR, was also studied. Hepatoma-bearing rats fed a WR diet
      exhibited hypercholesterolemia compared with normal rats fed the same diet.
      Feeding hepatoma-bearing rats a PGBR or BR diet suppressed hepatoma-induced
      hypercholesterolemia, and enhanced fecal bile acid excretion and the activity of
      cholesterol 7alpha-hydroxylase, the rate-limiting enzyme of bile acid
      biosynthesis, in the microsomal fraction of the liver without affecting
      cholesterol synthesis in the host liver of hepatoma-bearing rats. These results
      suggest that PGBR as well as BR suppresses hypercholesterolemia induced by
      hepatoma growth by up-regulating cholesterol catabolism.

PMID- 16464477
TI  - Melatonin prevents oxidant damage in various tissues of rats with
      hyperthyroidism.
AB  - Impairment of thyroid functions brings about pathological changes in different
      organs of body. Findings of in vivo and in vitro studies indicate that thyroid
      hormones have a considerable impact on oxidative stress. Melatonin reduces
      oxidative damage through its free radical eliminating and direct anti-oxidant
      effects. The present study was undertaken to determine how a 3-week period of
      intraperitoneal melatonin administration affected oxidative damage caused in
      experimental hyperthyroidism in rat. The experimental animals were divided into 3
      groups (control, hyperthyroidism, hyperthyroidism+melatonin). Malondialdehyde
      (MDA) and glutathione (GSH) levels were determined in different tissues. MDA
      levels in cerebral, liver and cardiac tissues in hyperthyroidism group were
      significantly higher than those in control and hyperthyroidism+melatonin
      supplemented groups (p<0.001). The highest GSH levels were observed in the group
      that was administered melatonin in addition to having hyperthyroidism (p<0.001).
      These results show that hyperthyroidism increased oxidative damage in cerebral,
      hepatic and cardiac tissues of rat. Melatonin supplementation may also suppress
      oxidative damage.

PMID- 16464478
TI  - Pharmacological evaluation of an [(123)I] labelled imidazopyridine-3-acetamide
      for the study of benzodiazepine receptors.
AB  - In vitro binding of the iodinated imidazopyridine, N',N'-dimethyl-6-methyl-(4'
      [(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [(123)I]IZOL to
      benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is
      reported. Saturation experiments showed that [(123)I]IZOL, bound to a single
      class of binding site (n(H)=0.99) on adrenal and kidney mitochondrial membranes
      with a moderate affinity (K(d)=30 nM). The density of binding sites was 22+/-6
      and 1.2+/-0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No
      specific binding was observed in mitochondrial-synaptosomal membranes of brain
      cortex. In biodistribution studies in rats, the highest uptake of [(123)I]IZOL
      was found 30 min post injection in adrenals (7.5% ID/g), followed by heart,
      kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution
      of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL
      and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the
      uptake of [(123)I]IZOL by 30% (p<0.05) in olfactory bulbs and by 51-86% (p<0.01)
      in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p<0.01)
      in the rest of the brain and the blood. Diazepam, a mixed CBR-PBBS drug,
      inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32%
      to 44% (p<0.01) but with no effect on brain uptake and in blood concentration.
      Flumazenil, a central benzodiazepine drug and haloperidol (dopamine
      antagonist/sigma receptor drug) displayed no effect in [(123)I]IZOL in peripheral
      organs and in the brain. [(123)I]IZOL may deserve further development for imaging
      selectively peripheral benzodiazepine binding sites.

PMID- 16464479
TI  - Phenacetin acts as a weak genotoxic compound preferentially in the kidney of DNA
      repair deficient Xpa mice.
AB  - Chronic use of phenacetin-containing analgesics has been associated with the
      development of renal cancer. To establish genotoxicity as a possible cause for
      the carcinogenic effect of phenacetin, we exposed wild type and DNA repair
      deficient Xpa-/- and Xpa-/-/Trp53+/- mice (further referred as Xpa and Xpa/p53
      mice, respectively), carrying a reporter lacZ gene, to 0.75% (w/w) phenacetin
      mixed in feed. Xpa mice completely lack the nucleotide excision repair pathway,
      and as such they are sensitive to some classes of genotoxic compounds. Phenacetin
      exposure induced a significant increase of lacZ mutations in the kidney of both
      Xpa and Xpa/p53 mice. A minor response was found in liver, whereas no lacZ
      mutation induction was observed in the spleen of these animals. Interestingly,
      the observed phenacetin-induced mutant frequencies were higher in male than those
      found in female mice. This gender difference is probably due to a difference in
      metabolic rate. Phenacetin-induced mutations mainly consisted of point mutations
      rather than deletions. The mutational spectra in the kidney of treated WT and Xpa
      mice were quite similar. Taken together, these results demonstrate that the human
      carcinogen phenacetin acts as a weak genotoxic agent in an in vivo mouse model
      system.

PMID- 16464480
TI  - Reversal of neuropathic pain by alpha-hydroxyphenylamide: a novel sodium channel
      antagonist.
AB  - Sodium (Na) channel blockers are known to possess antihyperalgesic properties. We
      have designed and synthesized a novel Na channel antagonist, alpha
      hydroxyphenylamide, and determined its ability to inhibit both TTX-sensitive (TTX
      s) and TTX-resistant (TTX-r) Na currents from small dorsal root ganglion (DRG)
      neurons. alpha-Hydroxyphenylamide tonically inhibited both TTX-s and TTX-r Na
      currents yielding an IC(50) of 8.2+/-2.2 microM (n=7) and 28.9+/-1.8 microM
      (n=8), respectively. In comparison, phenytoin was less potent inhibiting TTX-s
      and TTX-r currents by 26.2+/-4.0% (n=8) and 25.5+/-2.0%, respectively, at 100
      microM. alpha-Hydroxyphenylamide (10 microM) also shifted equilibrium gating
      parameters of TTX-s Na channels to greater hyperpolarized potentials, slowed
      recovery from inactivation, accelerated the development of inactivation and
      exhibited use-dependent block. In the chronic constriction injury (CCI) rat model
      of neuropathic pain, intraperitoneal administration of alpha-hydroxyphenylamide
      attenuated the hyperalgesia by 53% at 100mg/kg, without affecting motor
      coordination in the Rotorod test. By contrast, the reduction in pain behavior
      produced by phenytoin (73%; 100mg/kg) was associated with significant motor
      impairment. In summary, we report that alpha-hydroxyphenylamide, a sodium channel
      antagonist, exhibits antihyperalgesic properties in a rat model of neuropathic
      pain, with favorable sedative and ataxic side effects compared with phenytoin.

PMID- 16464481
TI  - Sequential ordering of morphed faces and facial expressions following temporal
      lobe damage.
AB  - A card ordering task was developed to evaluate the role of the temporal lobe in
      perceiving subtle featural displacements of faces that contribute to judgments of
      facial expression and identity. Individuals with varying degrees of temporal lobe
      damage and healthy controls were required to manually sort cards depicting morphs
      of facial expressions or facial identities so that the cards were sequentially
      ordered from one morph endpoint to another. Four morph progressions were used-
      three emotion morphs (neutral-to-anger, neutral-to-fear, and fear-to-anger) and
      an identity morph. Five exemplars were given per morph type. Debriefing verified
      that participants were using feature-level cues to sort the cards. A patient with
      bilateral amygdala damage due to epilepsy did not differ in her sorting abilities
      from unilateral temporal lobectomy patients or controls. In contrast, a post
      encephalitic patient with widespread left temporal lobe damage showed impairments
      that were most marked on the fear-to-anger and identity sorts. These results show
      that amygdala-damaged individuals can use information contained in facial
      expressions to solve tasks that rely on feature-level analysis, which recruits
      processing in other temporal lobe regions involved in making fine featural
      distinctions.

PMID- 16464482
TI  - Structure of anthocyanin from the blue petals of Phacelia campanularia and its
      blue flower color development.
AB  - The dicaffeoyl anthocyanin, phacelianin, was isolated from blue petals of
      Phacelia campanularia. Its structure was determined to be 3-O-(6-O-(4'-O-(6-O-(4'
      O-beta-d-glucopyranosyl-(E)-caffeoyl)-beta-d-glucopyranosyl)-(E)-caffeoyl)-beta-d
      glucopyranosyl)-5-O-(6-O-malonyl-beta-d-glucopyranosyl)delphinidin. The CD of the
      blue petals of the phacelia showed a strong negative Cotton effect and that of
      the suspension of the colored protoplasts was the same, indicating that the
      chromophores of phacelianin may stack intermolecularly in an anti-clockwise
      stacking manner in the blue-colored vacuoles. In a weakly acidic aqueous
      solution, phacelianin displayed the same blue color and negative Cotton effect in
      CD as those of the petals. However, blue-black colored precipitates gradually
      formed without metal ions. A very small amount of Al(3+) or Fe(3+) may be
      required to stabilize the blue solution. Phacelianin may take both an inter- and
      intramolecular stacking form and shows the blue petal color by molecular
      association and the co-existence of a small amount of metal ions. We also
      isolated a major anthocyanin from the blue petals of Evolvulus pilosus and
      revised the structure identical to phacelianin.

PMID- 16464483
TI  - Modeling interchild differences in pharmacokinetics on the basis of subject
      specific data on physiology and hepatic CYP2E1 levels: a case study with toluene.
AB  - The objective of the present study was to evaluate the magnitude of
      interindividual variability in the internal dose of toluene in children of
      various age groups, on the basis of subject-specific hepatic CYP2E1 content and
      physiology. The methodology involved the use of a previously validated
      physiologically based pharmacokinetic (PBPK) model, in which the intrinsic
      clearance for hepatic metabolism (CL(int)) was expressed in terms of the CYP2E1
      content. The adult toluene PBPK model, with enzyme content-normalized CL(int),
      facilitated the calculation of child-specific CL(int) based on knowledge of
      hepatic CYP2E1 protein levels. The child-specific physiological parameters,
      except liver volume, were computed with knowledge of age and body weight, whereas
      physicochemical parameters for toluene were kept age-invariant based on available
      data. The actual individual-specific liver volume (autopsy data) was also
      included in the model. The resulting model was used to simulate the blood
      concentration profiles in children exposed by inhalation, to 1 ppm toluene for 24
      h. For this exposure scenario, the area under the venous blood concentration vs.
      time curve (AUC) ranged from 0.30 to 1.01 microg/ml x h in neonates with low
      CYP2E1 concentration (<3.69 pmol/mg protein). The simulations indicated that
      neonates with higher levels of CYP2E1 (4.33 to 55.93 pmol/mg protein) as well as
      older children would have lower AUC (0.16 to 0.43 microg/ml x h). The latter
      values were closer to those simulated for adults. Similar results were also
      obtained for 7 h exposure to 17 ppm toluene, a scenario previously evaluated in
      human volunteers. The interindividual variability factor for each subgroup of
      children and adults, calculated as the ratio of the 95th and 50th percentile
      values of AUC, was within a factor of 2. The 95th percentile value of the low
      metabolizing neonate group, however, was greater than the mean adult AUC by a
      factor of 3.9. This study demonstrates the feasibility of incorporating subject
      specific data on hepatic CYP2E1 content and physiology within PBPK models for
      evaluating the age, interchild and population variability of internal dose for
      use in risk assessment of inhaled volatile organics.

PMID- 16464485
TI  - Inhibition of calcineurin by polyunsaturated lipids.
AB  - From earlier studies on calcineurin, the presence of multiple double bonds in
      putative inhibitors was hypothesized as critical features for effective
      inhibition. Polyunsaturated fatty acids were tested as inhibitors of calcineurin
      and found to inhibit the phosphatase activity of calcineurin although effective
      inhibition was observed only in the absence of calmodulin. Calmodulin and fatty
      acids seemed to compete for the enzyme with the activation curve of calmodulin
      shifted approximately 100-fold in the presence of 50 microM eicosa-11Z,14Z
      dienoic acid (20:2, n-6) or 50 microM eicosa-8Z,11Z,14Z-trienoic acid (20:3, n
      6). Leukotriene B4 and derivatives also were screened as inhibitors. The most
      effective inhibition was caused by the 6-trans,12-epi-leukotriene B4 with an IC50
      of 16.4 microM for the inhibition of calcineurin with pNPP as the substrate.
      Lipoxins A4 and B4 likewise caused inhibition in the presence of calmodulin with
      an IC50 of 42.7 microM for lipoxin B4. There was no protection by calmodulin, as
      found with the inhibition by the fatty acids. These data support the hypothesis
      that effective inhibition is bolstered by the presence of conjugated double bonds
      in the inhibitor. Consideration of cis- and trans-orientation of the double bonds
      suggests that presentation of the delocalized electron density is also a factor
      in effective inhibition of calcineurin.

PMID- 16464484
TI  - Hypoxia- and radiation-inducible, breast cell-specific targeting of retroviral
      vectors.
AB  - To facilitate a more efficient radiation and chemotherapy of mammary tumours,
      synthetic enhancer elements responsive to hypoxia and ionizing radiation were
      coupled to the mammary-specific minimal promoter of the murine whey acidic
      protein (WAP) encoding gene. The modified WAP promoter was introduced into a
      retroviral promoter conversion (ProCon) vector. Expression of a transduced
      reporter gene in response to hypoxia and radiation was analysed in stably
      infected mammary cancer cell lines and an up to 9-fold increase in gene
      expression demonstrated in comparison to the respective basic vector. Expression
      analyses in vitro, moreover, demonstrated a widely preserved mammary cell
      specific promoter activity. For in vivo analyses, xenograft tumours consisting of
      infected human mammary adenocarcinoma cells were established in SCID/beige mice.
      Immunohistochemical analyses demonstrated a hypoxia-specific, markedly increased
      WAP promoter-driven expression in these tumours. Thus, this retroviral vector
      will facilitate a targeted gene therapeutic approach exploiting the unique
      environmental condition in solid tumours.

PMID- 16464486
TI  - Response of microbial activities in two contrasting soils to 4-nonylphenol
      treated with biosolids.
AB  - In the application of biosolids on agricultural lands, 4-nonylphenol (4-NP) in
      soils is an important environmental concern because of its associated estrogenic
      risk to animals and human beings. Incubation experiments that involved the mixing
      of two contrasting soils (A: calcareous sandy soil; B: acidic clayey soil) and
      biosolids in 4-NP were performed to examine the effect of 4-NP on the rate of
      production of CO2, the mineralization of N and the microbial biomass, by
      considering the biodegradation of 4-NP for the evaluation of soil health. The
      experimental results indicated that the half-life (t1/2) of 4-NP increased with
      the supplementary concentration of 4-NP (80, 160 and 240 mg kg(-1)) in the two
      soils, and the t1/2 values in the soil A are always lower than that in soil B.
      The 4-NP supplement in the biosolids reverses C mineralization in soil B more
      than it does in soil A, but it reverses N mineralization in soil A more than in
      soil B. The aeration status and microbial population of the biosolids treated
      soils are key factors in determining the time course of 4-NP degradation
      associated with the microbial activities. The 4-NP was biodegraded mainly by
      bacteria, and the effect on C and N mineralization of 4-NP input is determined by
      a balance of the reductions in microbial biomass C (MBC) and N (MBN). After
      destruction in microbial cell membrane and protein structures by the 4-NP, C and
      N mineralization, MBC and MBN were subsequently followed by a final decline phase
      for the later period of incubation.

PMID- 16464488
TI  - Howiesons Poort lithic raw material procurement patterns and the evolution of
      modern human behavior: a response to Minichillo (2006).

PMID- 16464487
TI  - Monitoring of iodinated X-ray contrast media in surface water.
AB  - A monitoring programme was carried out in order to determine iodinated X-ray
      contrast media (ICM) in the River Danube and to investigate the raw water quality
      for drinking water production at Langenau waterworks. The study revealed that the
      maximum concentrations of ICM (over 500 ng l(-1) for diatrizoic acid and
      iopamidol) were found in 2h-composite samples taken from the downstream of the
      Ulm/Neu-Ulm metropolitan area. By means of a concentration profile over one month
      the highest ICM concentrations were observed on weekdays. The extended data
      evaluation with principal component analysis shows that the upstream and
      downstream samples had different pattern of variations in ICM concentration and
      also demonstrates a clear change in ICM composition by the discharge of municipal
      wastewater. In addition to load profiles of ICM, time-dependent plots of
      principal component 1 exhibited peaks, indicating a short-term discharge of ICM
      between the two sampling sites. In conclusion, a point source for ICM
      contamination between the sampling sites in Ulm upstream and Leipheim downstream
      seems to be the reasonable explanation for peak ICM concentrations. Due to the
      observed high variations of ICM concentrations in river, the evaluation of
      natural waters by means of a single analysis is not representative.

PMID- 16464490
TI  - Plasma concentrations of 13,14-dihydro-15-keto prostaglandin F2-alpha (PGFM),
      progesterone and estradiol in pregnant and nonpregnant diestrus cross-bred
      bitches.
AB  - The canine corpus luteum (CL) typically sustains elevated plasma progesterone
      concentrations for 2 months or more, with a peak approximately 15-25 days after
      ovulation, followed by a slow decline. The processes involved in the slow,
      protracted regression of the CL over the remaining 1.5-2-month period in
      nonpregnant bitches and until shortly prepartum in pregnant bitches are not well
      characterized. The rapid luteolysis that occurs immediately prepartum appears to
      be a result of a prepartum rise in peripheral PGF. The potential role of PGF in
      the slow regression process in the several weeks preceding parturition and in
      nonpregnant bitches after 15-25 days after ovulation is not known. Therefore,
      plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2-alpha (PGFM),
      progesterone (P4) and estradiol (E2) were determined and compared in bitches
      during nonpregnant diestrus (n = 9) or pregnancy (n = 8). During the gradual
      decrease in plasma concentrations of progesterone in both groups, the P4 pattern
      appeared unrelated to changes in either E2 or PGFM concentrations. The PGFM
      pattern was different between diestrus and pregnant bitches (P > 0.01); there was
      an apparent progressive but slow increase in PGFM in pregnant bitches from Days
      30 to 60, followed by a large increase prior to parturition; concentrations
      declined immediately postpartum. However, there were no increases in PGFM during
      the same interval in nonpregnant bitches. Mean estradiol concentrations were
      sporadically elevated during the last third of pregnancy and less so in
      nonpregnant diestrus; there was no acute prepartum increase in estradiol
      associated with the PGFM increase. In summary, although there were no apparent
      changes in peripheral PGF2alpha concentration involved in regulating the slow
      protracted phase of luteal regression in nonpregnant bitches, modest increases in
      PGFM may play a role in ovarian function after mid-gestation in pregnant bitches.
      Furthermore, the acute prepartum rise in PGFM was not dependent on any
      concomitant increase in estradiol concentrations.

PMID- 16464489
TI  - Remediation of bromate-contaminated groundwater in an ex situ fixed-film
      bioreactor.
AB  - Use of a pilot-scale fixed-film bioreactor was investigated for remediation of
      bromate contamination within groundwater. Bromate reduction with stoichiometric
      production of bromide was observed, providing supporting evidence for complete
      reduction of bromate with no production of stable intermediates. Reduction of 87
      90% bromate from an influent concentration of 1.1 mg L(-1) was observed with
      retention times of 40-80 h. Lower retention times led to decreases in bromate
      reduction capability, with 11.5% removal at a 10 h retention time. Nitrate
      reduction of 76-99% from a 30.7 mg L(-1) as NO(3)(-) influent was observed at
      retention times of 10-80 h, although an increase in nitrite production to 2.7 mg
      L(-1) occurred with a 10 h retention time. Backwashing was not required, with the
      large plastic packing media able to accommodate biomass accumulation without
      decreases in operational efficiency. This study has provided proof of concept and
      demonstrated the potential of biological bromate reduction by fixed-film
      processes for remediation of a bromate contaminated groundwater source.

PMID- 16464491
TI  - Development to the blastocyst stage of parthenogenetically activated in vitro
      matured porcine oocytes after solid surface vitrification (SSV).
AB  - The effects of solid surface vitrification (SSV) on viability and parthenogenetic
      development of in vitro matured (IVM) porcine oocytes was investigated in the
      present study. Cumulus-free IVM porcine oocytes were subjected either to SSV or
      SSV combined with a cytochalasin B (CB) pre-treatment (SSV+CB) or all steps of
      SSV but without cooling (toxicity control=TC; toxicity control with CB pre
      treatment=TC+CB). Oocyte viability was evaluated by plasma membrane integrity and
      esterase activity measured by a combined staining with fluorescein diacetate,
      propidium iodide and Hoechst 33342. Surviving oocytes were parthenogenetically
      activated then cultured in vitro (IVC) for 6 days. The proportion of live oocytes
      after vitrification was significantly lower than that of the TC, TC+CB and the
      control groups, regardless of the CB pre-treatment. Treatment of oocytes with
      cryoprotectants did not decrease the rates of surviving oocytes. After activation
      of oocytes, the proportion of cleaved embryos was significantly higher in the
      SSV+CB (P<0.05) than that of the SSV group. Nevertheless, significantly more
      oocytes cleaved (P<0.05) in the TC, TC+CB and the control groups. On Day 6, the
      rate of blastocysts in the SSV and SSV+CB groups did not differ significantly.
      The number of oocytes developing to blastocyst and the mean number of blastomeres
      per embryo were significantly higher (P<0.05) in the TC, TC+CB and the control
      compared with that of the SSV and SSV+CB groups. To our knowledge, this is the
      first report on parthenogenetic development to blastocysts of porcine oocytes
      vitrified at the metaphase-II stage. Results indicate that the high
      concentrations of cryoprotectants were not harmful for in vitro development, and
      that CB pre-treatment may increase survival and development of SSV vitrified
      porcine oocytes.

PMID- 16464492
TI  - Reinforcement effect of adhesively luted fiber reinforced composite versus
      titanium posts.
AB  - OBJECTIVE: The aim of the present study was to investigate the influence of the
      rigidity of different post materials (titanium versus glass fiber reinforced
      composite [FRC]) on the fracture resistance of endodontically treated teeth
      (ETT). METHOD: Forty-eight caries-free maxillary central incisors were randomly
      assigned to six groups (n=8). After endodontic treatment, teeth of four groups
      were flattened 2mm above and two groups at the cemento-enamel junction (CEJ). As
      control, specimens of one group received neither composite build-up nor post, and
      teeth were left empty (E). In another group only a resin composite build-up was
      placed (C). In two groups, both titanium and FRC posts were inserted. One group
      with titanium (2/T) and FRC (2/FRC) post received a 2mm deep ferrule preparation.
      For one group with titanium (0/T) and FRC (0/FRC) post no ferrule design was
      provided. All-ceramic crowns were adhesively luted on all specimens. Specimens
      were exposed to thermomechanical loading and finally statically loaded until
      failure. RESULTS: The median fracture load values (min-max) were: E=317 (242
      404); C=387 (335-475); 0/FRC=352 (0-440); 2/FRC=502 (326-561); 0/T=420 (0-548),
      2/T=517 (416-653). Statistically significant differences were computed between E,
      C, 2/FRC, 0/T and 2/T; between C, 2/FRC and 2/T; between 0/FRC, 2/FRC and 2/T;
      between 0/T and 2/T regarding maximum fracture load. SIGNIFICANCE: Fracture
      resistance of ETT is not influenced by the rigidity of the post material. The
      combination of ferrule preparation and endodontic post results in higher load
      resistance after TML than any other build-up design.

PMID- 16464493
TI  - Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes.
AB  - STAT5 is constitutively phosphorylated in leukemic cells in approximately 70% of
      acute myeloid leukemia (AML) patients. To identify kinase candidates potentially
      responsible for STAT5 phosphorylation, we used liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) mass spectrometry to detect phosphoproteins in AML cell
      lines. We established TEL-ARG and BCR-ABL fusion proteins as the mechanism
      underlying STAT5 phosphorylation in HT-93 and KBM-3 cells, respectively. In
      addition, we identified a JAK2 pseudokinase domain mutation in HEL cells and
      using siRNA downregulation, established JAK2 as the kinase responsible for
      phosphorylating STAT5. This study illustrates the benefit of LC-MS/MS mass
      spectrometry and siRNA for the identification of novel targets and mutations.

PMID- 16464495
TI  - Child abuse in religiously-affiliated institutions: long-term impact on men's
      mental health.
AB  - OBJECTIVE: To describe the long-term impact of physical and sexual abuse of boys
      by someone in a trusting, non-familial relationship. This clinical study reports
      on the psychological functioning of men (N = 76) with substantiated claims
      against a residential religiously-affiliated institution for multiple and severe
      incidents of sexual, physical, and/or emotional abuse during childhood. The abuse
      was perpetrated by several adults in positions of authority and trust at the
      institution. METHODS: Each participant received a clinical interview and was
      administered psychological tests and a structured interview for DSM-IV diagnoses.
      The same clinician completed all of the assessments. RESULTS: DSM-IV criteria
      were met for current PTSD (42%), alcohol (21%), and mood-related disorders (25%).
      Over one-third of the sample suffered chronic sexual problems, and over one half
      had a history of criminal behavior. CONCLUSIONS: The clinical findings provide
      direction for assessing victims of historical abuse, and underscore the
      importance of awareness, prevention, and treatment needs for those who have been
      abused in institutional settings. Conclusions are limited due to participants'
      involvement in civil action, unknown pre-existing conditions, and the lack of a
      suitable comparison group.

PMID- 16464494
TI  - Trisomy 19 as the sole chromosomal abnormality in proliferative chronic
      myelomonocytic leukemia.
AB  - Distinct morphologic and clinical features associated with specific chromosomal
      abnormalities have been described in subgroups of myelodysplastic syndromes
      (MDS), which often are losses or gains and only rarely translocations. Among 103
      consecutive MDS patients diagnosed and karyotyped at the Albert-Ludwigs
      University of Freiburg (ALU) between 1993 and 1999, two chronic myelomonocytic
      leukemias (CMMoL) displayed trisomy 19 (+19) as the sole chromosomal abnormality.
      Three further CMMoL cases with +19 as the single abnormality, two of which
      previously reported, were collected from other centers. Four of the five patients
      presented with leukocytosis and splenomegaly, and an increased number of ringed
      sideroblasts was observed in two cases. Treatment was low-dose Decitabine (cases
      1 and 2), oral steroids (case 3), hydroxyurea (case 4), and daunorubicin/Ara-C
      (case 5). Transformation to acute myeloid leukemias (AML) occurred in three/five
      patients (cases 1, 2, and 4) 26, 12, and 22 months after diagnosis of CMMoL,
      respectively. We conclude that +19 as the sole anomaly is a rare but recurrent
      change in CMMoL, in particular of the proliferative type. It is at present
      unclear which gene(s) located on chromosome 19 might have a functional role for
      the development of this phenotype.

PMID- 16464496
TI  - Child abuse potential among mothers of substance-exposed and nonexposed infants
      and toddlers.
AB  - OBJECTIVE: The purpose of this longitudinal study was to determine whether there
      were differences in child abuse potential among mothers who were nonusers, drug
      users who accepted treatment, and drug users who rejected offers of treatment,
      over the first 2 years of their children's lives. METHOD: Participants were
      mothers of 140 infants, classified into Nonuser (n = 48), Treatment (n = 72), or
      Refuser (n = 20) groups. The Child Abuse Potential (CAP) Inventory [Milner, J. S.
      1980. The Child Abuse Potential Inventory: Manual. Webster, NC: Psytec
      Corporation] was administered when infants were 4, 9, 12, 18, and 24 months.
      RESULTS: Results of mixed-model analyses of variances showed no group differences
      on CAP Inventory abuse scale scores. There were significant group differences in
      lie scale scores on the CAP Inventory, such that lie scale scores for the Nonuser
      group were significantly higher than lie scale scores for the Treatment group.
      CONCLUSIONS: Overall, results support the position that low-income women with
      many risk factors in their lives are at high risk for potential child abuse, but
      that their drug use status and drug treatment status does not differentiate them
      from their nonuser peers from a similar social and demographic background.

PMID- 16464497
TI  - Individual and combined effect of anthracene, cadmium, and chloridazone on growth
      and activity of SOD izoformes in three Scenedesmus species.
AB  - Short-term (12-48 h) experiments were carried out to examine the effect of
      anthracene (three-ring aromatic hydrocarbon), cadmium (CdCl(2)), and chloridazone
      (triazine herbicide), individually and in combination, on growth and SOD activity
      of three green algae Scenedesmus: S. subspicatus, S. obliquus, and S. microspina,
      grown in a batch-culture system. The relative toxicity of chemicals to algae was
      anthracene > chloridazone >> cadmium. The species revealed similar growth
      sensitivity to individual chemicals after 24 h of exposure but there were
      differences between them when exposed to their combinations. Two methods were
      used to determine the modes of interaction effects of the chemical combinations;
      both led to the same results, with two exceptions of all 36 variants examined. In
      general, mixtures of two and three chemicals behaved toward algal growth mainly
      in an antagonistic manner (20 cases), whereas additive and synergistic
      interaction occurred 13 and 3 times, respectively. Antagonism was the most
      frequently observed to growth of S. obliquus; antagonistic interaction and
      additive effect was noted in relation to S. subspicatus, while response of S.
      microspina depended markedly on applied combination. There is a relationship
      between SOD activity and growth response to stress. The markedly higher level of
      SOD isoforms activities was noticed in cells (especially S. microspina and S.
      obliquus) exposed to 12 h to combined chemicals, as compared to individually
      treated and control cells. SOD activities in cells of three Scenedesmus grown 24
      h were similar in all experimental variants and after 48 h of exposure
      significantly decreased in almost all cases (especially in S. subspicatus). There
      were no differences observed between SOD profiles obtained for all variants
      examined. Chloroplasts seems to be the main target site of interaction effects of
      dissimilarly acting chemicals.

PMID- 16464498
TI  - Expression of two vitellogenin genes (vg1 and vg3) in fathead minnow (Pimephales
      promelas) liver in response to exposure to steroidal estrogens and androgens.
AB  - In this study, we describe the sequence for the fathead minnow (Pimephales
      promelas) vitellogenin 3 gene (vg3) and compare the responses of vg1 and vg3
      following exposure to steroidal estrogens and androgens. The fathead minnow vg3
      sequence is the second nucleotide sequence described in teleosts, following the
      original description of this isoform in zebrafish (Danio rerio). Following a
      brief water exposure (24h) to 2, 5, and 10 ng/L 17alpha-ethynylestradiol (EE2),
      both vg1and vg3 were upregulated in male liver. However, levels of vg3 induction
      were four orders of magnitude lower than levels of induction of vg1. Suppression
      of vg in female liver following exposure to 50 or 500 ng/L of the synthetic
      androgen 17beta-trenbolone occurs at similar magnitude for both vg1 and vg3
      isoforms. The results of this study support the use of vg1 as an indicator of
      estrogenic exposure in male fish and indicate the potential for vg1 and /or vg3
      for use as indicators of androgenic exposure.

PMID- 16464499
TI  - Potential role of sulfide and ammonia as confounding factors in elutriate
      toxicity bioassays with early life stages of sea urchins and bivalves.
AB  - This work reports some considerations on the possible contribution of sulfide and
      ammonia to the toxicity of elutriate samples of sediments from the Venice lagoon,
      tested with a battery of bioassays using early life stages of the sea urchin
      Paracentrotus lividus and the oyster Crassostrea gigas. A comparison of ammonia
      or sulfide concentration in the test matrix, matrix toxicity, and the sensitivity
      limit of bioassays for ammonia or sulfide were used in evaluating toxicity data.
      Results highlighted that sperm cell and embryo toxicity of elutriates were not
      affected by sulfides. Neither was any direct relationship shown between elutriate
      toxicity and ammonia concentration. Most elutriates had ammonia concentrations
      below the sensitivity limit of acute test methods, while the more sensitive
      subchronic toxicity tests were affected by ammonia interference in some samples.

PMID- 16464500
TI  - Genetic and morphological diversity in populations of Nucella lapillus (L.;
      neogastropoda) in response to tributyltin contamination.
AB  - During the past three decades, North Atlantic populations of dogwhelks have been
      severely reduced in numbers, due to imposex and female sterility caused by TBT.
      We examined the relationship between the known history of female sterility and
      the present genetic diversity (measured by five allozyme-loci) and phenotypic
      variance (measured by nine quantitative characters) in six populations of Nucella
      lapillus along the coast of Norway. The environment of one of the populations was
      severely polluted with a vas deferens sequence index (VDSI) of 4.31, resulting in
      24% sterile females. The environment of four of the other five populations was
      moderately polluted (VDSI 3.31-3.97, 0-1.6% sterile females), while the last
      population was unpolluted (VDSI 0.02, 0% sterile females). The six populations
      did not differ significantly with respect to genetic diversity. However, the
      population from the most polluted area had greater phenotypic variation in shell
      size, compared to all other populations. The results indicate that although TBT
      has had severe local negative effects on N. lapillus populations, it has not
      caused a reduction in long-term adaptive potential.

PMID- 16464501
TI  - High-throughput, functional screening of the anti-HIV-1 humoral response by an
      enzymatic nanosensor.
AB  - The impact of antibodies on the target's epitope conformation is a major
      determinant of HIV-1 neutralization and a potential contributor to disease
      progression. We explore here a conformation-sensitive enzymatic nanosensor for
      the high-throughput functional screening of human anti-HIV-1 antibodies in sera.
      When displaying a model epitope from a gp41 immunodominant region (Env residues
      from 579 to 613), the sensing signal quantitatively distinguishes between
      adaptive and non-adaptive antibody binding. By using this tool, we have
      identified IgG4 as the immunoglobulin subpopulation most efficient in the
      structural modification of the target epitope.

PMID- 16464502
TI  - High-valent iron complexes with tetraamido macrocyclic ligands: structures,
      Mossbauer spectroscopy, and DFT calculations.
AB  - Iron complexes of tetraamido macrocyclic ligands (TAML) are unique synthetic
      oxidation catalysts. In general, the central Fe(III) ion (S=3/2) is surrounded by
      four, almost planar, deprotonated amide-N sigma-donors although the full suite
      with new generation systems includes some substitution of amides with related
      donor functionalities. Oxidation under different conditions affords a variety of
      high-valent forms of iron-TAMLs. This review provides a summary and discussion of
      structural and spectroscopic features of complexes oxidized by one equivalent
      above the ferric state. These comprise Fe(IV)-TAML high spin (S=2) and
      intermediate spin (S=1) systems, wherein the oxidation equivalent can be taken
      from the metal (Fe(IV)) or the ligand (TAML radical-cation Fe(III)), and coupled
      spin (S=0) systems of mu-oxoiron(IV) dimers. The discussion is principally based
      on data obtained by X-ray crystallography, Mossbauer spectroscopy, and density
      functional theory calculations.

PMID- 16464503
TI  - A critical look at the diagnostic value of culture-confirmation in childhood
      tuberculosis.
AB  - OBJECTIVES: To describe the clinical presentation, delay in diagnosis and
      treatment initiation, and outcome of culture-confirmed childhood tuberculosis.
      METHODS: Retrospective study of children<13 years of age at Tygerberg Children's
      Hospital, Cape Town, South Africa with culture-confirmed tuberculosis seen
      January 2002-June 2003. Data were collected by review of hospital and clinic
      records. RESULTS: Culture-confirmed tuberculosis was diagnosed in 184 children,
      median age 36 months; 26 (14.1%) were diagnosed clinically and treatment was
      started before admission. Tuberculosis was newly diagnosed in 158 children; 127
      (80.4%) were clinically diagnosed and 31 (19.6%) were diagnosed only after
      culture result was known (culture-diagnosed). The median time from admission to
      diagnosis was 1 day (1-21 days) for clinically diagnosed, and 73 (34-178 days)
      for culture-diagnosed children. Treatment was initiated by hospital physicians in
      all 127 clinically diagnosed and 14/31 culture-diagnosed children. Of the 17
      culture-diagnosed children not started on treatment, 4 were subsequently
      diagnosed on clinical grounds and treated at clinic level, 8 were found in good
      health, 4 failed to follow-up and 1 neonate died before the culture result was
      known. CONCLUSIONS: In symptomatic children, the vast majority could be
      confidently diagnosed on clinical grounds. However, culture-confirmation remains
      valuable to establish drug susceptibility.

PMID- 16464505
TI  - Measurement of coordination of object manipulation in non-human primates.
AB  - We present a modification of the automated movement assessment panel [Gash DM,
      Zhang Z, Umberger G, Mahood K, Smith M, Smith C, et al. An automated movement
      assessment panel for upper limb motor functions in rhesus monkeys and humans. J
      Neurosci Methods 1999;89:111-7] that incorporates a three-dimensional load cell
      to record forces applied by monkeys while manipulating food targets. The absolute
      force-time integral (total absolute impulse) is used to characterize the total of
      the applied forces over time as the food (carrot chip with a hole punched through
      the center) is manipulated and lifted from a flat surface (easiest task) and
      threaded over a straight rod (medium difficulty) or curved rod (highest
      difficulty). The total impulse can be measured even on unsuccessful attempts to
      acquire the food. Thus, it can be used to evaluate changes in performance even
      before successful acquisition occurs as in learning or recovery following a
      nervous system insult. We show from tests in three rhesus monkeys that the total
      absolute impulse measure is sensitive to task complexity, learning and lesion of
      frontal lobe motor areas (in one case) and that there is good reliability in day
      to-day performance (even with long periods between performances) after the monkey
      has learned the task. Importantly, the task requires minimal training as the
      monkeys can be successful on even the most difficult of these tasks with one or
      two training sessions, yet performance improvements continue to occur over
      several testing sessions. Furthermore, the three levels of task difficulty permit
      analysis of a progression of ability.

PMID- 16464507
TI  - Depressive symptomatology in young people with Gilles de la Tourette Syndrome-- a
      comparison of self-report scales.
AB  - BACKGROUND: Few studies have examined depressive symptomatology in children and
      adolescents with Tourette Syndrome (TS) using standardised measures and none have
      compared different self-report scales in the context of TS. METHODS: Seventy-two
      consecutive young people attending a TS clinic were evaluated using standardised
      rating scales for TS and associated behaviours, severity and psychopathology. All
      the patients completed the Birleson Depression Self Report Scale (BDSRS) and the
      Children's Depression Inventory (CDI). RESULTS: A strong correlation was noted
      between BDSRS and CDI. Depression scores were also noted to correlate with
      Obsessive Compulsive Behaviours (OCB) and Attention Deficit Hyperactivity
      Disorder (ADHD). Other correlates of depressive symptomatology included current
      severity of TS as indicated by Yale Global Tic Severity Rating Scale (YGTSS) and
      the lifetime cumulative severity as evidenced by scores on the Diagnostic
      Confidence Index (DCI). LIMITATIONS: The study was undertaken in a tertiary
      referral specialized clinic for TS thus limiting the generalizability of the
      findings, and the study did not include any control subjects. CONCLUSIONS: The
      results provide support for the need and usefulness of both BDSRS and CDI as
      screening tools for depressive symptoms in children and adolescents with TS.
      Furthermore, the findings suggest the possibility of a complex inter-relationship
      between TS severity, comorbid OCB and ADHD as well as the occurrence of
      depression.

PMID- 16464506
TI  - The 5HTTLPR polymorphism of the serotonin transporter gene is associated with
      affective temperaments as measured by TEMPS-A.
AB  - BACKGROUND: Increasing evidence supports the notion of a continuum between
      affective temperaments and major mood disorders, suggesting that these
      temperament types represent the subclinical manifestations of affective disorders
      and often present an increased vulnerability for these diseases. METHODS: The
      Hungarian rendition of the full-scale 110-item version of the TEMPS-A
      questionnaire and 5HTTLPR genotype was investigated in a sample of 139 unrelated
      Caucasian females with no current or lifetime Axis I psychiatric disorders.
      RESULTS: A significant association was found between the s allele and the TEMPS
      scores of the depressive, anxious, irritable, and particularly the cyclothymic
      temperaments; no such association emerged with respect to the hyperthymic
      temperament. LIMITATION: The database is entirely female. Given that the
      hyperthymic type predominates in males, our results could have been different if
      men were included in our sample. CONCLUSIONS: Our results are in good agreement
      with earlier studies reporting a strong association between the s allele of the
      5HTTLPR and major as well as subthreshold forms of depression, and extend this
      association to the normative temperament level. Indeed, these temperaments might
      best be regarded as proximate behavioural endophenotypes. Our data raise the
      provocative possibility that the genetic potential for mood episodes lies in
      these temperaments. Further studies are needed to delineate the role of gender in
      the associations under consideration, as well as to investigate the genetic
      background of the hyperthymia-mania part of the affective spectrum. Given that
      affective temperaments are widely distributed in the general population, the
      strategy employed by us is of potential public health significance in terms of
      detecting individuals in the community at risk for affective spectrum disorders.

PMID- 16464509
TI  - Genomic organization and expression of the expanded SCG/L/R gene family of
      Leishmania major: internal clusters and telomeric localization of SCGs mediating
      species-specific LPG modifications.
AB  - Stage-specific modifications to the abundant surface lipophosphoglycan (LPG)
      adhesin of Leishmania play critical roles in binding and release of the parasite
      during its infectious cycle in the sand fly, and control the ability of different
      fly species to transmit different parasite strains and species. In Leishmania
      major Friedlin V1, binding to a sand fly midgut lectin is mediated by side chain
      galactosyl (scGal) modifications of the LPG phosphoglycan (PG) repeats, while
      release occurs following arabinose-capping of scGals. Previously we identified a
      family of six SCG genes encoding PG scbeta-galactosyltransferases, and here we
      show that the extended SCG gene family (now termed SCG/L/R) encompasses 14
      members in three subfamilies (SCG, SCGL and SCGR). Northern blot and RT-PCR
      analyses suggest that most of the SCG/L/R genes are expressed, with distinct
      patterns during the infectious cycle. The six SCGR subfamily genes are clustered
      and interspersed with the two SCA genes responsible for developmentally regulated
      arabinosylation of PG scGals; relationships amongst the SCGR revealed clear
      evidence of extensive gene conversion. In contrast, the seven SCG 'core' family
      members are localized adjacent to telomeres. These telomeres share varying
      amounts of sequence upstream and/or downstream of the SCG ORFs, again providing
      evidence of past gene conversions. Multiple SCG1-7 RNAs were expressed
      simultaneously within parasite populations. Potentially, telomeric localization
      of SCG genes may function primarily to facilitate gene conversion and the
      elaboration of functional evolutionary diversity in the degree of PG sc
      galactosylation observed in other strains of L. major.

PMID- 16464508
TI  - Induction of hepatic choriogenin mRNA expression in male marine medaka: a highly
      sensitive biomarker for environmental estrogens.
AB  - Teleost choriogenins, precursors of the inner layer subunits of egg envelope,
      have been recently introduced as sensitive biomarkers for exposure to estrogenic
      compounds. In this study, two full-length cDNAs-ojChgH and ojChgL which encode
      the choriogenin H and L forms, respectively, were cloned from the marine medaka,
      Oryzias javanicus. The deduced protein sequences of ojChgH and ojChgL are highly
      similar to the corresponding homologues in the freshwater medaka (O. latipes)
      with identities of 77.2 and 87.6%, respectively. Phylogenetic analysis indicated
      that ojChgH and ojChgL are members of two different classes of liver-specific ZP
      domain containing proteins (ZPB and ZPC, respectively). Computer analysis of ca.
      2 kb of the 5'-flanking sequences of ojChgH and ojChgL revealed that both genes
      contain a number of putative estrogen response elements (EREs) and/or half-site
      EREs. In vivo mRNA expression patterns of the genes were examined by quantitative
      real-time RT-PCR. ojChgH is expressed exclusively in the liver while ojChgL is co
      expressed in the liver (major) and ovary (minor). Exposure of fish to waterborne
      17beta-estradiol (E2) at environmentally relevant concentrations (1, 5, 10 and
      100 ng/L) resulted in dose-dependent induction of both genes in the liver, with
      higher sensitivity and magnitude of induction in males than in females. In the
      male liver, induction of ojChgH is more sensitive to E2 than that of ojChgL and
      two other estrogen-responsive genes, estrogen receptor alpha (ojERalpha) and
      vitellogenin (ojVTG). The lowest-observed-effect concentration (LOEC) of E2 on
      induction of hepatic ojChgH mRNA is 1 ng/L. In the ovary, expression of ojChgL is
      non-responsive to E2 treatment. In conclusion, the present study suggested that
      induction of hepatic ojChgH mRNA in male fish may be a highly sensitive biomarker
      for exposure to environmental estrogens.

PMID- 16464510
TI  - Endomorphin synthesis in rat brain from intracerebroventricularly injected [3H]
      Tyr-Pro: a possible biosynthetic route for endomorphins.
AB  - In spite of concentrated efforts, the biosynthetic route of mu-opioid receptor
      agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH2 and Tyr-Pro-Phe-Phe
      NH2), discovered in 1997, is still obscure. We report presently that 30 min after
      intracerebroventricular injection of 20 or 200 microCi [3H]Tyr-Pro (49.9 Ci mmol(
      1)) the incorporated radioactivity was found in endomorphin-related tetra- and
      tripeptides in rat brain extracts. As detected by the combination of HPLC with
      radiodetection, a peak corresponding to endomorphin-2-OH could be identified in
      two of four extracts of "20 microCi" series. Radioactive peaks in position of
      Tyr, Tyr-Pro, Tyr-Pro-Phe or Tyr-Pro-Trp appeared regularly in both series and
      also in the "tetrapeptide cluster" constituted by endomorphins and their free
      carboxylic forms. In one of the four extracts in the "200 microCi" series a
      robust active peak in the position of endomorphin 2 could be detected.
      Intracerebroventricularly injected 100 nmol, but not 10 or 1000 nmol cold Tyr-Pro
      (devoid of opioid activity in vitro), caused a naloxone-reversible prolongation
      of tail-flick latency in rats, peaking between 15 and 30 min. We suggest that Tyr
      Pro may serve as a biosynthetic precursor to endomorphin synthesis.

PMID- 16464511
TI  - Assessing the efficacy of within-animal control strategies against E. coli O157:
      a simulation study.
AB  - A stochastic simulation model was used to assess the efficacy of potential
      measures to control the levels of Escherichia coli O157 within the bovine host.
      The model described E. coli O157 population sizes at several sites along the
      bovine gut and therefore only interventions that operate at an individual animal
      level could be evaluated. In order to use the model to evaluate the control
      strategies, it was necessary to make assumptions about how each strategy affected
      E. coli O157 populations in vivo. The within-animal conditions under these
      control strategies were modelled by adjusting the growth rates of E. coli O157 at
      specific sites of interest in the gut, based on these assumptions. The model
      simulated the population dynamics of an initial dose of E. coli O157 inoculated
      into an animal in the presence of inhibitory probiotics or antibiotics,
      bactericidal antibiotics or probiotics, and following fasting. Of the control
      strategies considered, the use of inhibitory probiotics appeared most promising
      and continued development of a suitable product is to be encouraged.

PMID- 16464504
TI  - mda-7/IL-24: multifunctional cancer-specific apoptosis-inducing cytokine.
AB  - "Differentiation therapy" provides a unique and potentially effective, less toxic
      treatment paradigm for cancer. Moreover, combining "differentiation therapy" with
      molecular approaches presents an unparalleled opportunity to identify and clone
      genes mediating cancer growth control, differentiation, senescence, and
      programmed cell death (apoptosis). Subtraction hybridization applied to human
      melanoma cells induced to terminally differentiate by treatment with fibroblast
      interferon (IFN-beta) plus mezerein (MEZ) permitted cloning of melanoma
      differentiation associated (mda) genes. Founded on its novel properties, one
      particular mda gene, mda-7, now classified as a member of the interleukin (IL)-10
      gene family (IL-24) because of conserved structure, chromosomal location, and
      cytokine-like properties has become the focus of attention of multiple
      laboratories. When administered by transfection or adenovirus-transduction into a
      spectrum of tumor cell types, melanoma differentiation associated gene
      7/interleukin-24 (mda-7/IL-24) induces apoptosis, whereas no toxicity is apparent
      in normal cells. mda-7/IL-24 displays potent "bystander antitumor" activity and
      also has the capacity to enhance radiation lethality, to induce immune-regulatory
      activities, and to inhibit tumor angiogenesis. Based on these remarkable
      attributes and effective antitumor therapy in animal models, this cytokine has
      taken the important step of entering the clinic. In a Phase I clinical trial,
      intratumoral injections of adenovirus-administered mda-7/IL-24 (Ad.mda-7) was
      safe, elicited tumor-regulatory and immune-activating processes, and provided
      clinically significant activity. This review highlights our current understanding
      of the diverse activities and properties of this novel cytokine, with potential
      to become a prominent gene therapy for cancer.

PMID- 16464513
TI  - Using discrete choice experiments to estimate a preference-based measure of
      outcome--an application to social care for older people.
AB  - This paper reports the results of a study that used discrete choice experiment
      (DCE) methodology to estimate quality weights for a of social care outcome
      measure. To reflect different states of need, a five-dimensional profile measure
      was developed. Experimental design techniques were used to derive a sample of
      states for which preferences were elicited. The DCE approach was employed to
      elicit values and regression techniques used to estimate a model that could
      predict index scores for all 243 possible outcomes. The utility model, estimated
      on the basis of 297 responses, had good test-retest reliability and converged
      with preferences elicited from a rating exercise.

PMID- 16464512
TI  - A simulation model for the study of the within-animal infection dynamics of E.
      coli O157.
AB  - Escherichia coli 0157 can cause serious illness, even death, in humans. There is
      some consensus that the main reservoirs of this harmful bacterium are the rumens
      and intestines of cattle. Hence, a stochastic model of the bovine gut was
      developed to investigate the in vivo population dynamics of E. coli O157. Because
      bacterial numbers can reach minimal levels, a stochastic system was considered,
      with a birth-death process being used to represent bacterial growth and decay
      dynamics throughout the gastrointestinal tract. Reinfection through ingestion of
      bacteria present in the environment was allowed to occur and the required
      clustered distribution of inter-event times was implemented through the use of a
      random hazard doubly stochastic Poisson process. Due to the inclusion of multiple
      compartments, a feedback mechanism and an interest in the non-equilibrium
      dynamics of the process, it was not possible to obtain an analytical
      representation of the process and therefore, a simulation study was used to
      obtain results. The within-animal model can be used to explore the efficacy of
      control measures which act at an individual animal level.

PMID- 16464514
TI  - Progressive truncation of the Non-Structural 1 gene of H7N1 avian influenza
      viruses following extensive circulation in poultry.
AB  - In order to support eradication efforts of avian influenza (AI) infections in
      poultry, the implementation of "DIVA" vaccination strategies, enabling the
      Differentiation of Infected from Vaccinated Animals have been recommended by
      international organisations. A system, based on the detection of antibodies to
      the Non-Structural 1 (NS1) protein of AI has been proposed but the success of
      such a system lies in the conservation of the NS1 protein among different AI
      isolates. With this in mind, the ns1 gene of 40 influenza A viruses isolated from
      a spectrum of avian species was sequenced and compared phylogenetically. The
      isolates included both low pathogenicity (LPAI) (n=22) and highly pathogenic
      (HPAI) (n=18) viruses of the H7 subtype and were representative of the avian
      influenza viruses that circulated in Northern Italy from 1999 to 2003. Size
      variation in the predicted amino acid sequence of each NS1 was revealed with two
      different levels of carboxy-terminal truncation being observed. Of the 40
      isolates analysed, 16 had a full-length NS1 protein of 230 aa, 6 had a truncated
      protein of 220 aa and 18 had an intermediate truncation resulting in a protein of
      224 aa. All of the H7N1 HPAI isolates possessed the intermediate carboxy-terminal
      truncation. In addition, all of the H7N1 LPAI viruses circulating at the
      beginning of the epidemic had a full length NS1 while those circulating towards
      the end of the period had a truncated protein. To determine whether modifications
      to NS1 could be a result of laboratory manipulation, two strains
      (A/ty/Italy/977/99 and A/ck/Italy/1082/99) with a full length NS1 were inoculated
      into 10-day-old embryonated chicken and 12-day-old embryonated turkey eggs via
      the allantoic route for 20 blind passages and sequenced at passages 3, 10, and
      20. No truncation was observed following these serial passages. To determine
      whether the truncation involved an immunogenic region of the NS1 protein a
      peptide spanning residues 219 aa to 230 aa was synthesized and tested in an
      indirect ELISA against sera obtained from turkeys experimentally infected with a
      virus strain known to have a full length NS1 protein. The peptide proved to be
      immunogenic highlighting the fact that the variations of the NS1 protein
      presented in this work must to be taken into consideration when developing a
      diagnostic test based on the identification of antibodies to the NS1 protein.

PMID- 16464515
TI  - Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation
      of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral
      ischemia in rats.
AB  - Hypoxia is a common cause of cell death and is implicated in many disease
      processes including stroke and chronic degenerative disorders. In response to
      hypoxia, cells express a variety of genes which allow adaptation to altered
      metabolic demands, decreased oxygen demands, and the removal of irreversibly
      damaged cells. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that
      regulates the adaptive response to hypoxia in cells. In this study, we reported
      an early, time-related, gradual up-regulation of HIF-1alpha, and a moderate
      increase in vascular endothelial growth factor (VEGF)- and erythropoietin (Epo)
      levels following transient focal ischemia. Moreover, we demonstrated, for the
      first time a specific localization of the pro-apoptotic regulator BNIP3 in
      striatal and cortical neurons after transient focal ischemia in rats. Prolonged
      intranuclear BNIP3 immunoreactivity was associated with delayed neuronal death.
      Experiments showed protein increases on Western blots of brain tissue with peaks
      at 48h after ischemia. Epo responds to ischemia in an early stage, whereas VEGF
      and BNIP3 accumulate in cells at later times after ischemia. This suggests the
      possibility that BH3-only proteins might be one of the major downstream effectors
      of HIF-1alpha in hypoxic cell death. These findings open the possibility that the
      hypoxia-regulated pro-apoptotic protein BNIP3 enters the nucleus and could
      interact with other proteins involved in DNA structure, transcription or mRNA
      splicing after focal brain ischemia.

PMID- 16464516
TI  - Sulfisoxazole, an endothelin receptor antagonist, protects retinal neurones from
      insults of ischemia/reperfusion or lipopolysaccharide.
AB  - Endothelins exert pathological effects in the eye and much interest centres on
      their role in causing retinal neuronal death in ischemic diseases like glaucoma.
      In the present study the influence of the non-selective endothelin antagonist,
      sulfisoxazole on raised intraocular pressure-induced ischemia to the rat retina
      was investigated. Moreover, in vitro studies on primary rat retinal cultures were
      undertaken to see whether sulfisoxazole is able to blunt the toxic effect of
      lipopolysaccharide (LPS) to retinal neurones. In order to determine whether
      sulfisoxazole provides protection to the retina the a- and b-wave amplitudes of
      the electroretinogram (ERG), the localisation of retinal choline
      acetyltransferase (ChAT), nitric oxide synthase (nNOS) and Thy-1 and the retinal
      mRNA levels of Thy-1 and FGF-2 were deduced in retinas subjected to ischemia in
      the absence or presence of sulfisoxazole. The results showed that the ischemia
      induced changes to the a- and b-wave amplitudes of the ERG and changes associated
      with the localisation of ChAT, nNOS and Thy-1 to be significantly blunted by
      sulfisoxazole. However, while the ischemia-induced changes to Thy-1 and FGF-2
      mRNAs were reduced by sulfisoxazole, the reduction was non-significant. The in
      vitro studies provided support for the protective effect of sulfisoxazole. Here,
      it was clearly shown that sulfisoxazole attenuated the elevation of nitric oxide
      (deduced by measuring nitrite) and the reduction in numbers of GABA-containing
      neurones caused by LPS. The present study provides evidence for the first time
      that endothelin antagonist can protect the retina from ischemic-like insults as
      occurs in glaucoma.

PMID- 16464517
TI  - Clusterin up-regulation following sub-lethal oxidative stress and lipid
      peroxidation in human neuroblastoma cells.
AB  - Clusterin/apolipoprotein J is a multifunctional protein up-regulated during
      various pathophysiological states. Since oxidative stress plays an important role
      in brain aging, and in many neurodegenerative disorders, to further understand
      the mechanistic underpinnings of clusterin expression, in this study, we examined
      clusterin expression in human neuroblastoma cells under conditions of increased
      production of reactive oxygen species and lipid peroxidation. Specifically, we
      analyzed clusterin mRNA and protein levels in human neuroblastoma IMR-32 and SH
      SY5Y cells following exposure to sub-lethal amounts of iron-ascorbate to induce
      an increase in reactive oxygen species generation and lipid peroxidation. Under
      such conditions, we observed a time-dependent up-regulation of clusterin protein
      and mRNA levels, detected by immunoblot analysis and RT-PCR, respectively. Given
      the known roles of clusterin, the results of the present study support the notion
      that an increase in clusterin expression may be a physiological defence mounted
      to reduce cell damage and maintain cell viability during periods of increased
      oxidative stress.

PMID- 16464518
TI  - Characterization of a viscerotropic yellow fever vaccine variant from a patient
      in Brazil.
AB  - Although the live attenuated yellow fever (YF) 17D vaccine is considered to be
      one of the safest vaccines in the world today, several cases of disease
      associated with administration of the vaccine have been reported, including YF
      vaccine-associated viscerotropic disease (YF-VAVD), which was first described in
      1996. All YF-VAVD isolates sequenced to date have shown very little genomic
      change when compared to their parental vaccine strains. In this study, we report
      the characterization of an isolate, BeH291597 (Brazil75), from a 1975 fatal case
      of YF-VAVD in Brazil. Comparison of Brazil75 with the genomic sequence of the
      parental 17DD vaccine strain revealed two amino acid substitutions (at positions
      M-49 and NS4B-240) that were unique to Brazil75. Although still a rare
      occurrence, this isolate suggests that YF-VAVD has been present much longer than
      previously recognized.

PMID- 16464519
TI  - Short-term atorvastatin treatment enhances specific antibody production following
      tetanus toxoid vaccination in healthy volunteers.
AB  - Statins possess anti-inflammatory and immunomodulatory properties beyond their
      cholesterol-lowering effects. To determine whether short-term atorvastatin
      treatment affects the acute phase and humoral immune responses to tetanus toxoid
      (TT) in normal healthy volunteers, we conducted a randomized, double blind,
      placebo-controlled trial. Twenty healthy volunteers were assigned a 10-day
      treatment with atorvastatin (40 mg) or placebo. All volunteers received a TT
      booster on the fifth day. Subjects in the atorvastatin group had a significant
      reduction in total and low-density lipoprotein cholesterol (both p<0.001).
      Unexpectedly, the production of anti-TT antibodies (predominately IgG1) was three
      fold higher in the atorvastatin group 15 days post-vaccination (2306 +/- 468
      versus 713+/-21 units, p = 0.008). Atorvastatin also suppressed the post
      vaccination rise in platelet and lymphocyte counts (both p<0.05). Acute phase
      parameters did not change significantly in either group. This study illustrates a
      novel immunomodulatory effect of atorvastatin raising the possibility of using
      HMG-CoA reductase inhibitors to enhance humoral responses to vaccination.

PMID- 16464520
TI  - An MF59-adjuvanted inactivated influenza vaccine containing A/Panama/1999 (H3N2)
      induced broader serological protection against heterovariant influenza virus
      strain A/Fujian/2002 than a subunit and a split influenza vaccine.
AB  - To test whether inactivated influenza vaccines distributed during the 2003-2004
      influenza season in the northern hemisphere were able to confer protection
      against the mismatched variant A/Fujian/411/2002 virus strain, we measured
      haemagglutination inhibiting (HI) antibodies in elderly subjects vaccinated with
      three inactivated vaccines against the homologous A/H3N2 vaccine strain
      (A/Panama) and against the mismatched A/Fujian strain. The results showed that,
      while 76 to 80% of elder people vaccinated with conventional vaccines had
      protected levels of antibodies against the A/Fujian heterovariant strain, those
      vaccinated with the MF59-adjuvanted vaccine have protective levels of antibodies
      in >98% of the cases. We conclude that MF59-adjuvanted vaccines confer protection
      also against influenza virus strains which are not fully matched with those
      included in the vaccine.

PMID- 16464521
TI  - Enhancement of immune responses to an HIV gp120 DNA vaccine by fusion to TNF
      alpha cDNA.
AB  - DNA vaccines have considerable potential for disease prophylaxis and therapy, but
      are generally poorly immunogenic. A number of means of enhancing immunogenicity
      have been assessed, including the co-expression of cytokines, the use of
      heterologous prime-boost regimes, and the addition of more conventional
      adjuvants. In this study we have assessed the effects on gp120 DNA immunogenicity
      of in-frame fusion of tumor necrosis factor alpha DNA to DNA encoding a large
      fragment of HIV gp120. The studies were performed using a DNA prime, protein
      boost regime and a heterologous boosting protein. Fusion of TNFalpha DNA enhanced
      Th1 related immune responses against both the priming and the boosting gp120. In
      frame fusion of interferon gamma-encoding DNA at the 5' end of the chimeric
      molecule, to create a tripartite fusion, had no additional effect on
      immunogenicity.

PMID- 16464522
TI  - Distribution of carbon 14 in the terrestrial environment close to French nuclear
      power plants.
AB  - For 10 years, (14)C measurements have been performed around French nuclear power
      plant sites, both in zones influenced and zones not influenced by gaseous
      releases. Examining the results from these measurements in the terrestrial
      environment shows that the discharges have a very slight impact on the
      radiocarbon level (with a relative increase in the specific activity of the order
      of 3 Bqkg(-1)C in the influenced areas). In correlation, there is a near
      negligible increase in dose, on average less than 0.1 microSvyr(-1), with
      reference to a dose from background radiation, which is of the order of 10
      microSvyr(-1). The deltaC13 values are very similar between the influenced zone
      and the non-influenced zone, with a mean of -27 per thousand. The mean DeltaC14
      varies from 101 per thousand in the non-influenced zone to 123 per thousand in
      the influenced zone. Moreover, a general reduction in (14)C concentration was
      found, with a time constant of the order of 95 years. The current level of (14)C
      specific activity in terrestrial environment is estimated to be 242+/-6 Bqkg(
      1)C.

PMID- 16464523
TI  - Reconstruction of defects in the head and neck with free flaps: 20 years
      experience.
AB  - Between March 1982 and December 2002 we did a total of 534 reconstructions with
      free flaps from various donor sites for 529 patients. The jejunum was the donor
      site in 181 reconstructions (34%), followed by the radial forearm flap in 173
      reconstructions (32%); 86% of the reconstructions were immediately after
      excisions. Surgical re-exploration was necessary in 37 patients (7%); the failure
      rate from necrosis of the flap was 5%. Factors associated with complications were
      American Society of Anesthesiology (ASA) class and age.

PMID- 16464524
TI  - The application of structure-based assessment to support safety and chemistry
      diligence to manage genotoxic impurities in active pharmaceutical ingredients
      during drug development.
AB  - Starting materials and intermediates used to synthesize pharmaceuticals are
      reactive in nature and may be present as impurities in the active pharmaceutical
      ingredient (API) used for preclinical safety studies and clinical trials.
      Furthermore, starting materials and intermediates may be known or suspected
      mutagens and/or carcinogens. Therefore, during drug development due diligence
      need be applied from two perspectives (1) to understand potential mutagenic and
      carcinogenic risks associated with compounds used for synthesis and (2) to
      understand the capability of synthetic processes to control genotoxic impurities
      in the API. Recently, a task force comprised of experts from pharmaceutical
      industry proposed guidance, with recommendations for classification, testing,
      qualification and assessing risk of genotoxic impurities. In our experience the
      proposed structure-based classification, has differentiated 75% of starting
      materials and intermediates as mutagenic and non-mutagenic with high concordance
      (92%) when compared with Ames results. Structure-based assessment has been used
      to identify genotoxic hazards, and prompted evaluation of fate of genotoxic
      impurities in API. These two assessments (safety and chemistry) culminate in
      identification of genotoxic impurities known or suspected to exceed acceptable
      levels in API, thereby triggering actions needed to assure appropriate control
      and measurement methods are in place. Hypothetical case studies are presented
      demonstrating this multi-disciplinary approach.

PMID- 16464525
TI  - The interpretation of occupational epidemiologic data in regulation and
      litigation: studies of auto mechanics and petroleum workers.
AB  - Epidemiologic data often serve as scientific basis for policies in regulation and
      opinions in litigation. The interpretation of epidemiologic data in both
      regulation and litigation is often challenged and debated. In this commentary, a
      wide range of issues concerning the interpretation of epidemiologic data in
      regulation and litigation are discussed. These issues include: case reports,
      study design, specificity of exposure, interview or recall bias,
      misclassification of occupation or exposure, confounding multiple exposures,
      confidence intervals and statistical power, selection of relevant studies,
      consistency of study results, study cohort definition, cohort membership
      misclassification, dilution effect, and subcohort or stratified analysis.
      Epidemiologic studies of auto mechanics and petroleum workers are used as
      examples to illustrate the importance of relying on sound epidemiologic
      principles in study interpretation. If these principles are not followed, the
      interpretation of epidemiologic studies will likely be erroneous and not useful
      to regulatory policy-makers or to those involved in litigation.

PMID- 16464526
TI  - Effects of peripubertal exposure to triphenyltin on female sexual development of
      the rat.
AB  - Triphenyltin (TPT) belongs to the group of organotin compounds which have been
      shown to affect reproduction in mammals. It is used as a fungicide and
      antifouling agent and the main source of human exposure is via food. We studied
      the effects of 2 or 6 mg TPT/kg bw on female sexual development using a
      modification of the Rodent 20-Day Thyroid/Pubertal Female Assay. Moreover, the
      effect of TPT before the onset of puberty was investigated. Beginning at
      postnatal day (PND) 23 female Wistar rats were treated per gavage until either
      PND 33 or the first estrus after PND 53. A delay in the completion of vaginal
      opening (VO) was observed in the 6 mg TPT group, while the 2mg TPT group showed
      advanced VO. Significantly increased ovarian weights were observed in both
      treatment groups. Steroid hormone levels and ovarian aromatase activity were
      affected after exposure to 6 mg TPT/kg bw, while treatment with 2mg TPT/kg bw
      resulted in minor changes of these endpoints. We conclude that peripubertal
      exposure to 6 mg TPT/kg bw, and to a lesser extent to 2mg TPT/kg bw, affects
      female sexual development.

PMID- 16464527
TI  - The multiple influences of glutathione on bromate genotoxicity: implications for
      the dose-response relationship.
AB  - Glutathione displays multiple roles in the oxidative genotoxicity of potassium
      bromate. On the one hand, reduced glutathione has a demonstrated role in the
      activation of bromate to species capable of oxidising DNA. However, if this
      activation should occur within the gut or extracellularly once bromate is
      absorbed, this may limit the ability of the chemical to oxidise cellular DNA in
      vivo. Moreover, glutathione may offer protection against the damaging species
      produced by its interaction with bromate. Finally, if bromate exposure of cells
      is sufficiently high to deplete glutathione, a secondary oxidative stress and
      associated DNA damage may occur. These observations would suggest non-linearity
      in the dose-response to DNA damage in vivo.

PMID- 16464528
TI  - The effect of polycarbophil gel (Replens) on bacterial vaginosis: a pilot study.
AB  - OBJECTIVE: To determine if use of intravaginal polycarbophil gel (Replens) for 1
      month will: (1) lower vaginal pH; (2) improve signs of bacterial vaginosis (BV).
      STUDY DESIGN: Seventeen women with BV self-administered polycarbophil gel every
      third day for 4 weeks in an open-label, prospective pilot study. Primary outcome
      measures included vaginal pH, presence of amines and Nugent scores. RESULTS: At
      week 4, there was improvement in Nugent scores, vaginal odor and clue cell count
      (p<0.05). Eleven women converted from amine positive to negative (73+/-20%).
      There was no significant change in vaginal pH. CONCLUSIONS: Polycarbophil gel is
      associated with improved signs of BV, although not vaginal pH.

PMID- 16464529
TI  - Orbital based electronic structural signatures of the guanine keto G-7H/G-9H
      tautomer pair as studied using dual space analysis.
AB  - Electronic structural signatures of the guanine-7H and guanine-9H tautomers have
      been investigated on an orbital by orbital basis using dual space analysis. A
      combination of density functional theory (B3LYP/TZVP), the statistical average of
      model orbital potentials (SAOP/TZ2P) method and outer valence Green's function
      theory (OVGF/TZVP) has been used to generate optimal tautomer geometries and
      accurate ionization energy spectra for the guanine tautomer pair. The present
      work found that the non-planar form for both of the guanine keto pair possesses
      lower energies than their corresponding planar counterparts, and that the
      canonical form of the guanine-7H tautomer has slightly lower total energy than
      guanine-9H. This latter result is in agreement with previous experimental and
      theoretical findings. In the planar guanine pair the geometric parameters and
      anisotropic molecular properties are compared, focusing on changes caused by the
      mobile proton transfer. It is demonstrated that the mobile proton only causes
      limited disturbance to isotropic properties, such as geometry and the energetics,
      of the guanine keto tautomer pair. The exception to this general statement is for
      related local changes such as the N((7))-C((8)) and C((8))-N((9)) bond length
      resonance between the single and double bonds, reflecting the nitrogen atom being
      bonded with the mobile proton in the tautomers. The mobile proton distorts the
      electron distribution of the tautomers, which leads to significant changes in the
      molecular anisotropic properties. The dipole moment of guanine-7H is altered by
      about a factor of three, from 2.23 to 7.05 D (guanine-9H), and the molecular
      electrostatic potentials also reflect significant electron charge distortion. The
      outer valence orbital momentum distributions, which were obtained using the plane
      wave impulse approximation (PWIA), have demonstrated quantitatively that the
      outer valence orbitals of the tautomer pair can be divided into three groups.
      That is orbitals 1a''-7a'' and 18a', which do not have visible alternations in
      the tautomeric process (which consist of either pi orbitals or are close to the
      inner valence shell); a second group comprising orbitals 19a'-22a', 25a', 26a',
      28a', 29a' and 31a', which show small perturbations as a result of the mobile
      hydrogen locations; and group three, orbitals 23a', 24a', 27a', 30a' and 32a',
      which demonstrate significant changes due to the mobile proton transfer and are
      therefore considered as signature orbitals of the G-7H/G-9H keto tautomeric
      process.

PMID- 16464530
TI  - The two-stage repair for severe primary hypospadias.
AB  - OBJECTIVES: The repair of severe primary hypospadias represents a major surgical
      challenge. After initial enthusiasm for single-stage procedures, many paediatric
      urologists have turned to the alternative two-stage approach after experiencing
      disappointing results. A single surgeon's experience of the two-stage procedure
      is reported. METHODS: Between 1998 and 2003, 62 boys underwent a two-stage
      reconstruction for primary hypospadias. Indications for staged repair included
      proximal meatus (mid-shaft [18 patients], peno-scrotal [23] or perineal [two]),
      moderate or severe chordee (38 patients), poor glans groove, and lichen
      sclerosis. Inner prepuce was the graft of choice. Median age was 27.6 months at
      completion of surgery and median follow-up was 26 months. RESULTS: All grafts
      took well and none of the 62 patients needed revision. One patient developed a
      haematoma. Maturation of the graft for at least six months ensured the best
      conditions for the second-stage closure. Overall the cosmetic and functional
      results after the second stage were excellent. The outcomes were determined by
      the parents' and surgeon's assessment of function and the cosmetic appearance.
      Complications included partial glans dehiscense (three patients), residual mild
      curvature (three) and meatal stenosis (three). CONCLUSION: The two-stage repair
      has proved to be a reliable and reproducible technique with a low complication
      rate in a difficult cohort of hypospadias patients. Inner preputial skin grafts
      take very successfully on the ventral surface of the penis, and splitting the
      glans enables a slit-like meatus to be achieved. Excellent cosmetic results can
      be anticipated.

PMID- 16464531
TI  - Evaluation of chemotherapy with magnetic resonance imaging in patients with
      regionally metastatic or unresectable bladder cancer.
AB  - OBJECTIVES: To determine whether the failure of chemotherapy in patients with
      regionally metastatic or unresectable transitional cell carcinoma (TCC) of the
      bladder can be predicted early in the course of chemotherapy with magnetic
      resonance (MR) imaging. METHODS: In this prospective study, 36 patients with
      regionally metastatic or unresectable TCC of the urinary bladder underwent MR
      imaging before and after two, four, and six cycles of chemotherapy with
      Methotrexate, Vinblastine, Adriamycin (doxorubicin) and Cisplatin (MVAC). The
      response after two cycles of MVAC was evaluated by using conventional tumour size
      parameters with unenhanced MR imaging and with changes in the time to the start
      of tumour or lymph node enhanced at fast dynamic contrast-enhanced MR imaging.
      The results obtained with these techniques were compared with the findings at
      histopathology in cystectomy or transurethral resection specimens that were
      obtained after chemotherapy. Duration of survival was defined as the time from
      the start of chemotherapy until disease-specific death. Kaplan-Meier curves were
      drawn to determine the difference in prognosis between responders and
      nonresponders. RESULTS: After two cycles of chemotherapy, the accuracy,
      sensitivity, and specificity in distinguishing responders from nonresponders with
      conventional MR imaging were 69%, 81%, and 50%, respectively. With the fast
      dynamic contrast-enhanced technique, accuracy, sensitivity, and specificity were
      92%, 91%, and 93% respectively. The median bladder cancer specific survival was
      28 months for all patients studied. Responders to chemotherapy at fast dynamic
      contrast-enhanced MR had better median disease-specific survival than
      nonresponders (42 months vs. 12 months [p<0.0001]). CONCLUSION: We can predict
      whether a patient will respond to chemotherapy after two cycles of chemotherapy
      with fast dynamic contrast-enhanced MR imaging.

PMID- 16464532
TI  - Management of BCG failures in superficial bladder cancer: a review.
AB  - OBJECTIVE: Review management of bacillus Calmette-Guerin (BCG) failures in
      superficial bladder cancer. METHOD: Search of published literature and meeting
      abstracts. RESULTS: Patients in whom BCG fails are not a uniform group. Failure
      cannot be predicted but high-risk patients can be identified. In case of failure
      and progression the outcome is bad. Conservative but investigative alternatives
      are BCG/interferon-alpha, intravesical hyperthermia/chemotherapy, or photodynamic
      therapy. Standard treatment in failing patients remains cystoprostatectomy.
      CONCLUSION: BCG failures need careful and individualized therapy in experienced
      hands.

PMID- 16464533
TI  - Ectoparasites of free-ranging pumas and jaguars in the Paraguayan Chaco.
AB  - Ectoparasites were collected from seven puma (Puma concolor) and seven jaguar
      (Panthera onca) live-captures (each representing six different animals) in the
      Paraguayan Chaco from 2002 to 2004. The same five species of ectoparasites were
      recovered from both host species: the flea, Pulex simulans (total on both hosts
      combined=30 male, 49 female), and the ticks, Amblyomma cajennense (1 male, 4
      female, 46 nymphs, 241 larvae), Amblyomma parvum (42 male, 25 female), Amblyomma
      tigrinum (1 male, 7 female, 34 larvae) and Amblyomma triste (4 male). There were
      no statistical differences between the prevalences (percent of hosts infested)
      for any of these ectoparasite species between the two host species, and only P.
      simulans showed a significantly higher mean intensity (mean no. of each
      ectoparasite species per infested host) on one of the host species (jaguar).
      Clearly, these two large carnivores share similar ectoparasite faunas in the
      Paraguayan Chaco. However, both carnivores occupy large geographical
      distributions in the New World and this study, combined with the few previous
      studies, suggests that their ectoparasite faunas differ slightly in different
      parts of their respective ranges.

PMID- 16464534
TI  - Flystrike in New Zealand: An overview based on a 16-year study, following the
      introduction and dispersal of the Australian sheep blowfly, Lucilia cuprina
      Wiedemann (Diptera: Calliphoridae).
AB  - A summary and analysis have been carried out on data from over 6000 instances of
      flystrike in sheep in NZ, over a 16-year period, using a self-referral system
      where farmers submitted larvae and related information. The study covered a
      period of establishment and subsequent countrywide spread of the exotic blowfly,
      Lucilia cuprina. Comparisons are drawn between flystrike as it was perceived by
      surveys carried out before the 1940s, and the current situation with L. cuprina
      as an added major impediment. Briefly, the main differences are an increase in
      the prevalence of flystrike, changes in the representation and relative influence
      of individual primary blowfly species, an extension of the flystrike 'season',
      and an apparent increase in the importance of footrot as a factor predisposing to
      flystrike. Otherwise, flystrike is still primarily a disease of ewe lambs that
      are struck predominantly around the tail and perineum, mainly because of faecal
      staining.

PMID- 16464535
TI  - Photobiomodulation partially rescues visual cortical neurons from cyanide-induced
      apoptosis.
AB  - Near-infrared light via light-emitting diode treatment has documented therapeutic
      effects on neurons functionally inactivated by tetrodotoxin or methanol
      intoxication. Light-emitting diode pretreatment also reduced potassium cyanide
      induced cell death, but the mode of death via the apoptotic or necrotic pathway
      was unclear. The current study tested our hypothesis that light-emitting diode
      rescues neurons from apoptotic cell death. Primary neuronal cultures from
      postnatal rat visual cortex were pretreated with light-emitting diode for 10 min
      at a total energy density of 30 J/cm2 before exposing to potassium cyanide for 28
      h. With 100 or 300 microM potassium cyanide, neurons died mainly via the
      apoptotic pathway, as confirmed by electron microscopy, Hoechst 33258, single
      stranded DNA, Bax, and active caspase-3. In the presence of caspase inhibitor I,
      the percentage of apoptotic cells in 300microM potassium cyanide was
      significantly decreased. Light-emitting diode pretreatment reduced apoptosis from
      36% to 17.9% (100 microM potassium cyanide) and from 58.9% to 39.6% (300 microM
      potassium cyanide), representing a 50.3% and 32.8% reduction, respectively. Light
      emitting diode pretreatment significantly decreased the expression of caspase-3
      elicited by potassium cyanide. It also reversed the potassium cyanide-induced
      increased expression of Bax and decreased expression of Bcl-2 to control levels.
      Moreover, light-emitting diode decreased the intensity of 5-(and -6) chloromethy
      2', 7-dichlorodihydrofluorescein diacetate acetyl ester, a marker of reactive
      oxygen species, in neurons exposed to 300 microM potassium cyanide. These results
      indicate that light-emitting diode pretreatment partially protects neurons
      against cyanide-induced caspase-mediated apoptosis, most likely by decreasing
      reactive oxygen species production, down-regulating pro-apoptotic proteins and
      activating anti-apoptotic proteins, as well as increasing energy metabolism in
      neurons as reported previously.

PMID- 16464536
TI  - Expression of the kidney injury molecule 1 in the rat cochlea and induction by
      cisplatin.
AB  - Cisplatin is a widely used chemotherapeutic agent whose dose-limiting side
      effects include ototoxicity and nephrotoxicity. Recent evidence indicates that
      cisplatin induces the expression of a novel protein, kidney injury molecule-1, in
      the renal proximal tubular epithelium to aid in regeneration. In this study, we
      determined whether kidney injury molecule-1 is expressed in the cochlea and is
      induced by cisplatin. Using reverse transcriptase polymerase chain reaction
      techniques, we have now identified kidney injury molecule-1 in the rat cochlea
      and in three different mouse transformed hair cell lines. Administration of
      cisplatin to rats produced hearing loss and induced kidney injury molecule-1 mRNA
      in the rat cochlea. Pretreatment of rats with lipoic acid, a scavenger of
      reactive oxygen species, significantly reduced cisplatin-induced hearing loss and
      kidney injury molecule-1 expression. Cisplatin also increased the expression of
      cochlear NOX3 mRNA, a member of the superoxide generating NADPH oxidase family of
      proteins recently identified in the cochlea, inhibition of which decreased kidney
      injury molecule-1 expression. Polymerase chain reaction performed on different
      regions of the cochlea indicated the presence of kidney injury molecule-1 mRNA in
      the lateral wall, organ of Corti and spiral ganglion. This distribution was
      confirmed by immunocytochemistry. Taken together, these data identify kidney
      injury molecule-1 as a novel cochlear injury molecule, whose expression is
      regulated by reactive oxygen species generated via the NADPH oxidase pathway.

PMID- 16464537
TI  - Long-term outcome of stereotactic radiosurgery (SRS) in patients with acoustic
      neuromas.
AB  - PURPOSE: To evaluate the effectiveness and long-term outcome of stereotactic
      radiosurgery (SRS) for acoustic neuromas (AN). PATIENTS AND METHODS: Between 1990
      and 2001, we treated 26 patients with 27 AN with SRS. Two patients suffered from
      neurofibromatosis type 2. Before SRS, a subtotal or total resection had been
      performed in 3 and in 5 patients, respectively. For SRS, a median single dose of
      13 Gy/80% isodose was applied. RESULTS: The overall actuarial 5-year and 10-year
      tumor control probability in all patients was 91%. Two patients developed tumor
      progression after SRS at 36 and 48 months. Nineteen patients (73%) were at risk
      of treatment-related facial nerve toxicity; of these, 1 patient developed a
      complete facial nerve palsy after SRS (5%). A total of 93% of the lesions treated
      were at risk of radiation-induced trigeminal neuralgia. Two patients (8%)
      developed mild dysesthesia of the trigeminal nerve after SRS. The hearing
      preservation rate in patients with useful hearing before SRS was 55% at 9 years.
      CONCLUSION: Stereotactic radiosurgery results in good local control rates of AN
      and the risk of cranial nerve toxicities is acceptable. As toxicity is lower with
      fractionated stereotactic radiotherapy, SRS should be reserved for smaller
      lesions.

PMID- 16464538
TI  - Efficacy of intensified hyperfractionated and accelerated radiotherapy and
      concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a
      randomized multicentric trial in advanced head-and-neck cancer.
AB  - PURPOSE: To prove an expected benefit of concurrent radiochemotherapy (RCT), a
      two-arm randomized multicentric study was performed. In a subgroup analysis the
      influence of pretherapeutical hemoglobin level (p-Hb) on survival under
      locoregional control (SLC) was tested. PATIENTS AND METHODS: The study included
      primarily untreated Stage III/IV (International Union Against Cancer [UICC])
      oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive
      either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5
      fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and
      29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy
      in 38 days in concomitant boost technique. RESULTS: After a median follow-up time
      of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with
      median SLC of 17 months and 11 months, respectively. Also overall survival (OS)
      shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT
      and 16 months for RT. However, the benefit in SLC and OS is not seen in
      hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer
      patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with
      higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further
      improve SLC. CONCLUSIONS: Hyperfractionated-accelerated RCT is superior to hf-acc
      RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve
      SLC.

PMID- 16464539
TI  - Special issue. Comparative cognition: A tribute to the contribution of William A.
      Roberts.

PMID- 16464540
TI  - Suspected transmission of methicillin-resistant Staphylococcus aureus between
      domestic pets and humans in veterinary clinics and in the household.
AB  - OBJECTIVE: To describe MRSA infection and colonization in household pets, and
      transmission of MRSA between animals and humans. METHODS: MRSA infection and
      colonization in household pets and human contacts were evaluated during
      investigations initiated after identification of MRSA infection or colonization
      of a household pet in order to determine if there had been transmission between
      animals and humans. All MRSA isolates were screened for Panton-Valentine
      leukocidin (PVL) genes by use of polymerase chain reaction, and isolate
      relatedness was determined by use of pulsed-field gel electrophoresis (PFGE).
      RESULTS: Investigations of six situations where MRSA was identified in one or
      more animals in a household or veterinary facility were performed. MRSA was
      isolated from 8 animals (5 dogs and 3 cats) with clinical infections, 1 cat that
      was in contact with 2 infected cats and 14/88 (16%) of household contacts or
      veterinary personnel. Both animal-to-human and human-to-animal transmission were
      suspected. An indistinguishable MRSA isolate was recovered from at least one
      human that was in contact with each animal case. All isolates were classified as
      Canadian epidemic MRSA-2, the predominant community-associated MRSA clone in
      humans in Canada. No isolates possessed genes encoding for the PVL. CONCLUSIONS:
      Transmission of MRSA between humans and animals, in both directions, was
      suspected. MRSA appears to be an emerging veterinary and zoonotic pathogen.

PMID- 16464541
TI  - Evaluation of a Pourquier ELISA kit in relation to agar gel immunodiffusion
      (AGID) test for assessment of the humoral immune response in sheep and goats with
      and without Mycobacterium paratuberculosis infection.
AB  - The present study was designed to evaluate a commercial ELISA kit (Institut
      Pourquier) for the diagnosis of ovine and caprine paratuberculosis under
      Australian conditions and to compare its accuracy with the existing AGID test.
      The sensitivity of the ELISA in sheep and goats was 34.9% and 56.4%, with a
      specificity of 98.8% and 100.0%, respectively. Sensitivity of AGID was 13.8% for
      sheep and 39.5% for goats, with specificity of 100.0% for both species. The
      sensitivity of the ELISA in sheep depended on the category of histological
      lesions. AGID and ELISA were conditionally independent, and appeared to detect
      overlapping but distinct subgroups of infected animals. The ELISA was
      significantly more sensitive than the AGID. The ELISA was simple to perform,
      robust and repeatable. Coefficients of variation of <12.0% were observed for
      positive and negative controls included on 193 plates over a 10-month period and
      there was a high level of intraassay repeatability with 12.0% of the duplicate
      samples having CV of >15.0%.

PMID- 16464543
TI  - Detection of early changes in sperm membrane integrity pre-freezing can estimate
      post-thaw quality of boar spermatozoa.
AB  - A recently developed triple staining (SNARF-1/YO-PRO-1/ethidium homodimer) was
      used to assess early changes in boar sperm membrane integrity (MI) with the
      results of cryopreservation procedures and to seek for correlations among MI
      spermatozoa in pre-freeze semen and its freezeability. Ejaculates from five boars
      were evaluated in the fresh and frozen-thawed (FT) state, and its freezeability
      defined as % of membrane intactness, MI% (MI%=% of FT-spermatozoa with intact
      membranes x 100 divided by the % of pre-freeze spermatozoa with intact membranes)
      estimated. Significant differences were found among boars for freezeability (MI%)
      and motility post-thaw (%). Interestingly, significant correlations were found
      between the percentage of YO-PRO-1-positive spermatozoa and freezeability
      (R=0.440, p<0.01), indicating this new triple staining can be used to safely
      disclose among ejaculates prior to freezing.

PMID- 16464542
TI  - Mutagenicity of the mycotoxin alternariol in cultured mammalian cells.
AB  - The mycotoxin alternariol (AOH) is an important contaminant of fruit and cereal
      products. Concern about exposure to low levels of AOH was raised after the
      disclosure that contamination of food with the AOH-producing species Alternaria
      alternata is associated with oesophagal cancer. Previously we have reported that
      AOH induces kinetochore-negative micronuclei in cultured Chinese hamster V79
      cells. The present study investigates the mutagenicity of AOH at the hypoxanthine
      guanine phosphoribosyltransferase (HPRT) gene locus in V79 cells and at the
      thymidine kinase (TK) gene locus in mouse lymphoma L5178Y tk(+/-) cells (MLC).
      Concentrations of 10 microM AOH and more gave rise to a significant and
      concentration-dependent induction of HPRT and TK mutations in V79 cells and in
      MLC, respectively. The mutagenic potency of AOH was about 50-fold lower than that
      of the established mutagen 4-nitroquinoline-N-oxide in both cell lines.
      Discrimination between small and large colonies in the TK assay revealed the
      predominant induction of small colonies, which are indicative for extensive
      chromosomal deletions and which correlated with the induction of micronuclei in
      MLC. The mutagenicity of AOH may have a bearing on the carcinogenicity of this
      mycotoxin.

PMID- 16464544
TI  - Characterization of seminal plasma proteins stabilizing the sperm viability in
      rainbow trout (Oncorhynchus mykiss).
AB  - In seminal plasma of the rainbow trout 12 proteins were detected by SDS-PAGE,
      ranging in their molecular weight from 135 to 16 kDa. Only those proteins with a
      molecular weight of 65, 54, 47 and 16 kDa occurred in all investigated seminal
      plasma samples. The 65 and the 54 kDa protein were found in highest quantities
      (34-45% of the total quantified protein content) followed by the 47 and the 16
      kDa protein (6-7% of the total quantified protein content). The 65 and the 48 kDa
      protein were glycoproteins as they stained positively with Periodic-Acid-Schiff
      reagent (PAS) specific for carbohydrates as well as with Coomassie Blue. The 90
      and 19 kDa protein were found in 82-91% of the investigated samples, all other
      proteins in lower frequencies of 36-73%. Seminal plasma contained no lipoprotein
      as staining with Sudan black B was negative. To find out which proteins
      positively affected the sperm viability (defined as sperm motility which could be
      activated) spermatozoa were incubated in sperm motility inhibiting saline
      solution containing different seminal plasma protein fractions. Sperm motility
      which could be activated after an incubation period of 48 h was highest in those
      fractions which shared the 54, 47, and the 16 kDa protein. When spermatozoa were
      incubated in untreated seminal plasma sperm viability was still higher than in
      the seminal plasma protein fractions indicating that other components of the
      seminal plasma positively affected sperm viability, too. The possible influence
      of seminal plasma proteins on sperm physiology is discussed.

PMID- 16464545
TI  - Effects of sperm concentration at semen collection and storage period of frozen
      semen on dairy cow conception.
AB  - The present study was based on data obtained from artificial inseminations (AIs)
      performed with cryopreserved semen from elite bulls used in the Norwegian
      breeding program. Semen was diluted to standardize the number of spermatozoa to
      18 million per AI dose. The aim of the study was to investigate whether the net
      sperm concentration at semen collection and the storage period in liquid nitrogen
      have any effect on probability of conception in dairy cattle. We demonstrated
      that the natural range of sperm concentration at semen collection within some of
      the bulls was associated with the probability of conception. However, no primary
      trend among bulls was found on the effect of sperm concentration at semen
      collection. This appears to be due to differences among bulls in their response
      to the dilution ratio of seminal plasma to extender. The effect of storage time
      was investigated in semen that had been stored between 1000 days and 2400 days in
      AI straws in liquid nitrogen at the AI center. Our findings showed that use of
      semen with the longest storage period, i.e. 1951-2400 days, resulted in a more
      than one percentage point lower probability of conception than semen with a
      shorter storage period. In conclusion, the net sperm concentration at semen
      collection, which affects the dilution ratio of seminal plasma to extender,
      should be considered individually among bulls to achieve optimal reproductive
      performance. Furthermore, this study gives support to the idea that a measurable
      degree of damage to the spermatozoa could occur during the preservation time in
      liquid nitrogen.

PMID- 16464546
TI  - Severity of cardiovascular disease in women: relation with exposure to endogenous
      estrogen.
AB  - OBJECTIVES: Coronary artery disease (CAD) is more common in men than in women.
      Endogenous sex steroids may be the main factor responsible, as long-term estrogen
      action appears to be protective. The aim of the study was to investigate the
      predisposing factors responsible for the severity of CAD in women. METHODS: One
      hundred and eight women (100 menopausal) undergoing coronary angiography were
      studied. Reproductive function was recorded. The severity of CAD was assessed by
      the number of arteries with severe stenosis, the presence of angina and
      myocardial infarctions (MI). RESULTS: The time since menopause (TSM) was
      significantly longer in women with angina and with MIs compared to those without
      (20.3+/-8.7 years versus 15.8+/-8.7 years and 22.6+/-8.6 years versus 18.1+/-8.9
      years, p<0.05), independently of chronological age. The age at menopause was
      significantly younger in women who had 2 MIs compared to those with 1 or 0 MI
      (41.5+/-3.5, 47.5+/-5.3 and 48.4+/-5.4 years, respectively; p=0.04); the total
      duration of menstrual cyclicity was inversely related to the number of MIs
      (35.6+/-5.8, 34.2+/-5.3 and 28.3+/-3.3 years, 0, 1 and 2 MIs, respectively;
      p=0.03). CONCLUSIONS: The severity of CAD in women referred for coronary
      angiography is correlated with measures of exposure to endogenous estrogen. Both
      the TSM and the age at menopause are aggravating factors for MI, independently of
      age. There is an independent protective effect of the duration of estrogen
      exposure on the number of MIs; this has not been reported before and supports the
      protective role of the length of exposure to endogenous estrogen, especially for
      the occurrence of MI in this selected group of women.

PMID- 16464547
TI  - Vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal
      Indian women.
AB  - OBJECTIVES: Osteoporosis is a common condition in postmenopausal women. Bone
      mineral density (BMD), the major determinant of osteoporotic fracture risk, has a
      particular genetic background. However, consensus on the association of BMD with
      specific gene locus has not been reached. The race and ethnicity specific
      divergence in association studies must be assessed to predict the susceptibility
      and therapeutic response of associated genes. We investigated the potential
      association of Vitamin D receptor (VDR) gene polymorphisms ApaI, BsmI, FokI and
      TaqI with BMD in 246 postmenopausal Indian women (average age 54.2+/-3.4 years).
      METHODS: The subjects were genotyped by PCR-RFLP and underwent BMD measurements
      at spine and hip by dual energy X-ray absorptiometery. RESULTS: The average BMD
      at spine and hip of women with genotypes aa, bb (presence of restriction sites
      for ApaI and BsmI), FF and TT (absence of restriction sites for FokI and TaqI)
      was more than 10% higher than those with genotypes AA, BB, ff and tt,
      respectively. The interaction between BsmI, ApaI and TaqI genotypes showed
      significant effect of BsmI-ApaI genotypes (p=0.052) in this combination on BMD.
      However, presence of T allele in combination showed positive influence on BMD.
      Within the group, genotypes BB, ff and tt were significantly prevalent in women
      with osteoporotic bone mass, tt and BB had significantly higher adjusted odd
      ratio (OR) for age more than 55years. CONCLUSION: Study reveals that VDR gene
      polymorphisms are associated with BMD in Indian women and perhaps, influence some
      determinant of bone metabolism. Ethnicity may attribute to frequency variation,
      however, allele impact remains same.

PMID- 16464548
TI  - Antigens and granularity of blood monocytes in relation to inflammatory markers
      and lipids in postmenopausal women.
AB  - OBJECTIVES: The menopause is associated with an increase of inflammatory markers
      (C-reactive protein, fibrinogen), cytokines (INFgamma, TNF, etc.) and blood
      lipoproteins. In vitro, CRP, LDL and fibrinogen can modulate or potentiate
      interleukines production by monocytes. The aim of this work was to study, the
      relationships in vivo between hs-CRP, fibrinogen, lipoproteins and the phenotype
      of circulating monocytes. METHODS: The monocytes phenotype, in postmenopausal
      women (n=26) without history of cardiovascular disease, was determined, by flow
      cytometry, measuring granularity and CD14, HLA-DR and CD62-L antigens expression.
      Blood monocytes were divided in CD14+dim monocytes (low CD14 expression) and
      CD14+bright monocytes (high CD14 expression). RESULTS: HLA-DR was negatively
      correlated with hs-CRP and fibrinogen. The relationships between ApoB, LDL/ApoB
      ratio and CD14 expression was restricted to the CD14+bright monocytes. Blood
      lipids, i.e. total cholesterol, LDL-c and ApoB were correlated with the
      granularity of both subsets. CD14+dim monocytes were characterized by a low
      granularity and CD62-L expression. CONCLUSIONS: Our data show that fibrinogen and
      hs-CRP are correlated with a reduced antigen-presenting capacity. Expression of
      CD14 on CD14+bright monocytes is negatively associated to atherogenic LDL. Blood
      monocytes granularity was positively correlated with serum lipids indicating that
      monocytes could uptake modified LDL in circulation and not restricted to
      subendothelial space.

PMID- 16464549
TI  - Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release
      capability.
AB  - The influence of the proportion of acrylamidomethyl-gamma-cyclodextrin (gamma-CD
      NMA) on loading and release of the hydrophobic triamcinolone acetonide (TA) and
      the hydrophilic propranolol (PR) by acrylic acid hydrogels was evaluated. gamma
      CD-NMA was synthesized by condensation of gamma-cyclodextrin (gamma-CD) with N
      (hydroxymethyl) acrylamide. Hydrogels were prepared with gamma-CD-NMA and sodium
      acrylate (3 M or 4 M), using N,N'-methylen(bisacrylamide) (BIS) as cross-linker,
      by free radical polymerization into glass moulds of 2 mm wide and were cut as
      discs (10 mm diameter). gamma-CD-NMA did not modify the pH-dependent swelling of
      the hydrogels, but significantly increased the swelling degree in the 40:60
      ethanol:water, medium in which TA can be dissolved. Hydrogels prepared with gamma
      CD-NMA above 5% (w/w of total monomers) showed a remarkably higher capacity to
      load TA, e.g., 33 mg/g dry hydrogel versus 0.6 mg/g dry hydrogel without gamma-CD
      NMA. This is explained by the formation of 1:1 inclusion complexes of TA with
      gamma-CD mers that overcomes the lack of interactions with the acrylic groups of
      the network. The release of TA in water, 0.1 N HCl, or pH 6.8 phosphate buffer
      was sustained for at least 24 h, whatever the pH and the composition of the
      medium used. In contrast, loading of PR from the water solutions was greater for
      hydrogels prepared with 3 M acrylate than with 4 M acrylate, irrespective to
      their content in gamma-CD-NMA, and in less than 2 h ca. 80% PR was released. The
      lower affinity of PR for the gamma-CD cavities, compared to the strong intensity
      of the electrostatic interactions with the acrylic acid groups, explains why the
      incorporation of gamma-CD-NMA did not increased the loading and control release
      capacity of the hydrogels of this hydrophilic drug. In summary, the
      copolymerisation of CD with acrylic monomers can provide highly hydrophilic pH
      sensitive networks which load large amounts of hydrophobic drugs and release them
      in a sustained way.

PMID- 16464550
TI  - Evidence of pitch processing in the N100m component of the auditory evoked field.
AB  - The latency of the N100m component of the auditory evoked field (AEF) is
      sensitive to the period and spectrum of a sound. However, little attention was
      paid so far to the wave shape at stimulus onset, which might have biased previous
      results. This problem was fixed in the present study by aligning the first major
      peaks in the acoustic waveforms. The stimuli were harmonic tones (spectral range:
      800-5000 Hz) with periods corresponding to 100, 200, 400, and 800 Hz. The
      frequency components were in sine, alternating or random phase. Simulations with
      a computational model suggest that the auditory-nerve activity is strongly
      affected by both the period and the relative phase of the stimulus, whereas the
      output of the more central pitch processor only depends on the period. Our AEF
      data, recorded from the right hemisphere of seven subjects, are consistent with
      the latter prediction: The latency of the N100m depends on the period, but not on
      the relative phase of the stimulus components. This suggests that the N100m
      reflects temporal pitch extraction, not necessarily implying that the underlying
      generators are directly involved in this analysis.

PMID- 16464552
TI  - Population genetic data of 15 tetrameric short tandem repeats (STRs) in Berbers
      from Morocco.
AB  - The allele frequency distribution of 15 short tandem repeats (STR) loci contained
      in the AmpFlSTR Identifiler PCR Amplification Kit (Applied Biosystems), was
      determined in two Berber populations from Asni and Bouhria, in Central and
      Eastern Morocco, respectively. A total of 209 individuals were typed. No
      deviations from the Hardy-Weinberg equilibrium were observed for Asni at the 15
      STRs loci whereas for the Bouhria samples, two loci (D5S818 and TH01) showed
      significant departures from Hardy-Weinberg expectations (after Bonferroni's
      correction). All loci are highly polymorphic and population differentiation tests
      showed that the Moroccan samples from Asni and Bouhria have significant
      differences in 4 out of 15 loci (D21S11, D7S820, D16S539 and TPOX). The aim of
      the study was to obtain accurate allele frequencies relevant for forensic
      applications. Comparative analyses between our population data and other
      population samples gathered from the literature are also presented.

PMID- 16464551
TI  - Analysis of hallucinogenic constituents in Amanita mushrooms circulated in Japan.
AB  - The constituents of seven mushrooms sold as Amanita muscaria or Amanita
      pantherina (five A. muscaria and two A. pantherina) and four "extracts purported
      to contain A. muscaria" products that are currently circulated in Japan were
      determined. All mushroom samples were identified as A. muscaria or A. pantherina
      by macroscopic and microscopic observation. The dissociative constituents,
      ibotenic acid (IBO) and muscimol (MUS), were extracted with 70% methanol twice
      and determined by gas chromatography/mass spectrometry. The IBO (as the
      hydrate)/MUS contents were in the range of <10-2845ppm/46-1052ppm in the cap of
      A. muscaria and 188-269ppm/1554-1880ppm in the cap of A. pantherina. In the caps,
      these compounds had a tendency to be more concentrated in the flesh than in the
      cuticle. On the other hand, the IBO/MUS contents in the stem were far lower than
      in the caps. In the "extracts purported to contain A. muscaria" products, IBO/MUS
      were detected below the lower limit of calibration curve (<10ppm/<25ppm) or not
      detected. However, these samples contained other psychoactive compounds, such as
      psychoactive tryptamines (5-methoxy-N,N-diisopropyltryptamine and 5-methoxy-N,N
      dimethyltryptamine), reversible monoamine oxidase inhibitors (harmine and
      harmaline) and tropane alkaloids (atropine and scopolamine), which were not
      quantified. This is the first report of the chemical analysis of Amanita
      mushrooms that are circulated in the drug market.

PMID- 16464553
TI  - Problems and prospects of modern lymph node imaging.

PMID- 16464554
TI  - MR contrast agents in lymph node imaging.
AB  - The detection of tumor metastases in lymph nodes is clinically important for
      tumor staging and therapy planning in cancer patients. However, differentiating
      between malignant and benign lymph nodes is still a problem because current
      imaging modalities rely only on the size and shape of the lymph nodes. Thus,
      small metastases in normal-sized lymph nodes can be missed, and it is difficult
      to differentiate enlarged nodes (benign hyperplasia versus malignant disease).
      Therefore, a specific lymphotropic contrast agent is needed to obtain a high
      contrast between functional and metastatic tissue. Contrast-enhanced MR
      lymphography is a noninvasive method for the analysis of the lymphatic system
      after interstitial (intracutaneous or subcutaneous) or intravenous application of
      contrast media. Interstitial MR lymphography using extracellular, liposomal,
      polymeric, lipophilic or particulate contrast agents results in high accumulation
      in regional lymph nodes. The systemic administration of a lymphotropic contrast
      medium is needed to address each individual lymph node. Ultrasmall
      superparamagnetic iron oxide particles are in late-stage clinical development for
      this indication, but they take 24h to show sufficient contrast. Recently, a
      gadolinium-type contrast agent (Gadofluorine M) was described that detected lymph
      node metastases within 60 min of intravenous injection.

PMID- 16464555
TI  - An overview of MR arthrography with emphasis on the current technique and
      applicational hints and tips.
AB  - Magnetic resonance (MR) arthrography has been investigated in every major
      peripheral joint of the body, and has been proven to be effective in determining
      the integrity of intraarticular ligamentous and fibrocartilaginous structures and
      in the detection or assessment of osteochondral lesions and loose bodies in
      selected cases. Several methods could be used to create arthrogram effect during
      MR imaging, however, direct MR arthrography using diluted gadolinium as the
      contrast agent is the most commonly used technique and is the most reliable of
      all. MR arthrography is useful for demonstrating labrocapsular-ligamentous
      abnormalities and distinguishing partial thickness rotator cuff tears from focal
      full thickness tears in the shoulder, identifying or excluding recurrent tears
      following meniscal operations in the knee, demonstrating perforations of the
      triangular fibrocartilage complex (TFCC) and ligaments in the wrist, showing
      labral tears in the hip, diagnosing ligament tears in the ankle and identifying
      osteochondral lesions or loose bodies in any of the aforementioned joints. In
      this article, an overview of techniques of MR arthrography is provided with
      emphasis on direct MR arthrography using diluted gadolinium as the contrast
      agent. The current applications of the technique in major peripheral joints are
      reviewed, with emphasis given to the shoulder joint where the role of this
      technique has become well established.

PMID- 16464556
TI  - Inoperable aggressive mesenteric fibromatosis with ureteric fistula. Case report
      and literature review.
AB  - The purpose of our report is to illustrate an aggressive case of mesenteric
      fibromatosis in a 17-year-old girl with a ureteric fistula and to review imaging
      and pathological features, natural history and treatment options of this disease.
      Our patient underwent computed tomography that revealed a widespread intra
      abdominal mass. The necrotic centre of this mass had a fistulous communication
      with the right ureter. Fibromatoses represent a spectrum of uncommon benign
      conditions characterised by proliferating fibrous tissue. The deep intra
      abdominal form of mesenteric fibromatosis (MF), one of the rare subtypes of the
      'fibromatoses' or 'desmoid tumours', grows rapidly and may become extensive.
      Surgery provides good results in limited disease and non-surgical modalities in
      cases of unresectable and residual disease.

PMID- 16464557
TI  - Simultaneous determination of formic acid and formaldehyde in pharmaceutical
      excipients using headspace GC/MS.
AB  - Formic acid and its esters, as well as formaldehyde, are trace impurities that
      are often present in pharmaceutical excipients. These trace impurities can
      potentially react with amino and/or hydroxyl groups in drugs to form significant
      levels of degradants. To select the appropriate excipients for a stable
      formulation, a gas chromatography/mass spectrometry (GC/MS) method was developed
      and validated for the rapid screening of trace amounts of residual formic acid,
      its esters and formaldehyde in pharmaceutical excipients. Samples were dissolved
      or dispersed in acidified ethanol to convert formic acid and formaldehyde to
      ethyl formate and diethoxymethane, respectively. Identification was conducted
      using a GC/MS system under scan mode and quantified using a selected ion
      monitoring (SIM) mode. Evaluation of the mass spectra of ethyl formate and
      diethoxymethane in the samples indicated that the method is specific. The limits
      of quantitation of the method were 0.5 ppm for formic acid and 0.2 ppm for
      formaldehyde. The precision of the method was demonstrated by the acceptable
      R.S.D. (<or=10%) over a linear range of 0.5-10,000 ppm. The accuracy of the
      method was within 80-120% over the linearity range. The amounts of formic acid
      and formaldehyde in commonly used pharmaceutical excipients is reported.

PMID- 16464559
TI  - Simultaneous determination of lamivudine and stavudine in antiretroviral fixed
      dose combinations by first derivative spectrophotometry and high performance
      liquid chromatography.
AB  - Two methods are described for the simultaneous determination of lamivudine (3TC)
      and stavudine (d4T) in combined pharmaceutical tablets. The first method depends
      on first derivative UV-spectrophotometry with zero-crossing measurement
      technique. The first derivative absorbances at 280 and 300 nm were selected for
      the determination of stavudine and lamivudine, respectively. The second method is
      based on the separation of both drugs by high performance liquid chromatography
      using methanol:water (20:80) as the mobile phase at 0.6 ml/min on a reverse phase
      column with detection at 270 nm. Both the methods showed good linearity,
      reproducibility and precision. No spectral or chromatographic interferences from
      the tablet excipients were found. The proposed methods were suitably applied to
      the assay of commercial formulations. The procedures were rapid, simple and
      suitable for routine quality control application.

PMID- 16464558
TI  - Stability indicating simultaneous determination of domperidone (DP),
      methylparaben (MP) and propylparaben by high performance liquid chromatography
      (HPLC).
AB  - A simple, specific and precise high performance liquid chromatographic method has
      been developed and validated for the simultaneous determination of methylparaben
      (MP), propylparaben (PP), and domperidone (DP) in oral suspension. Isocratic
      mobile phase consists of 0.5% w/v aqueous ammonium acetate buffer:methanol, 40:60
      (v/v). Column containing octylsilyl chemically bonded to porous silica particles
      (Optimapak, OP C8, 150 mmx4.6 mm, 5 microm, stainless steel analytical column
      from RS tech) is used as stationary phase. The detection is carried out using
      variable wavelength UV-vis detector set at 280 nm. The solutions are
      chromatographed at constant flow rate of 1.0 mL/min. The method separates MP, PP,
      DP and droperidol (DR) impurity in less than 12 min with good resolution, peak
      shapes and minimal tailing. Retention times (RT) for MP, PP, DP and DR are about
      3.4, 7.0, 9.0 and 10.9 min, respectively. Linearity range and percent recoveries
      for MP, PP and DP are 90-270, 10-30, 50-1500 microg/mL and 100.30%, 100.78% and
      100.48%, respectively. Method was validated according to ICH guidelines and
      proved to be suitable for stability testing, homogeneity testing and quality
      control of these compounds in pharmaceutical preparations.

PMID- 16464560
TI  - A novel RT-PCR approach for detection and characterization of citrus viroids.
AB  - Citrus plants are natural hosts of five viroid species and a large number of
      sequence variants. Because of their small size, viroids lend themselves to
      various RT-PCR approaches for their detection and further characterization. The
      one-step RT-PCR approach proposed here is based on the synthesis of viroid-cDNA
      by reverse transcription at 60 degrees C using a viroid specific 27-mer primer
      followed by standard second strand synthesis plus PCR amplification with various
      primer pairs. According to the primers used, full or partial length viroid-DNA is
      obtained. The technique avoids amplicon contamination in routine diagnosis. The
      suitability of the technique has been demonstrated using several nucleic acid
      extraction procedures and different viroid infected host species. The
      homogenization of tissue inside sealed plastic bags followed by nucleic acid
      extraction using a SDS/potassium acetate method is recommended because of its
      efficiency, simplicity and low cost. This extraction procedure, when coupled to
      the one-step RT-PCR approach, can be useful to avoid cross-contamination during
      routine diagnosis. A PCR strategy capable of discriminating between mild and
      severe strains of CEVd and identifying cachexia-inducing isolates of HSVd, is
      also described.

PMID- 16464561
TI  - Penicillin-resistant Streptococcus pneumoniae in Lebanon: the first nationwide
      study.
AB  - A total of 123 clinical isolates of Streptococcus pneumoniae were collected from
      all over Lebanon and tested for their susceptibility to penicillin: 30.1% were
      susceptible (minimum inhibitory concentration (MIC) < or = 0.06 microg/mL), 56.1%
      were intermediately susceptible (MIC 0.09-1.0 microg/mL) and 13.8% were resistant
      (MIC > 1.0 microg/mL). The oxacillin disk screening test detected all penicillin
      resistant isolates, but erroneously designated two penicillin-intermediate
      isolates as penicillin susceptible. All isolates were consistently susceptible to
      levofloxacin, but cross-resistance between penicillin and the three tested
      cephalosporins was frequently noted. The in vitro activity of
      amoxicillin/clavulanic acid paralleled that of penicillin; however, 92.7% of the
      isolates were designated as susceptible based on the recommended interpretive cut
      off point (MIC < or = 2/1 microg/mL). This discrepancy represents a paradox that
      deserves serious consideration.

PMID- 16464562
TI  - In vitro activities of non-traditional antimicrobials alone or in combination
      against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter
      baumannii isolated from intensive care units.
AB  - The aim of this study was to assess the in vitro activity of a number of non
      traditional antibiotics (colistin, azithromycin, doxycycline and rifampicin)
      against multidrug-resistant (MDR) strains of Pseudomonas aeruginosa and
      Acinetobacter baumannii isolated from Intensive Care Units (ICUs). We also used
      the checkerboard method to determine whether combinations of colistin with
      another non-traditional antibiotic or meropenem act synergistically against these
      strains. Thirty-five P. aeruginosa and 25 A. baumannii strains that were found to
      be MDR were included the study. Isolates were collected from the specimens of
      patients in ICUs from 2001 to 2003. All isolates were identified by standard
      methods and stored at -20 degrees C until use. Antibiotic powders of
      azithromycin, doxycycline, rifampicin, meropenem and colistin were obtained from
      their manufacturers. Minimum inhibitory concentrations (MICs) were determined by
      the agar dilution method on Mueller-Hinton agar. Five strains of A. baumannii and
      five strains of P. aeruginosa, all of which had different MIC values for
      colistin, were selected for the synergy study using the checkerboard titration
      method. The susceptibility results for doxycycline and meropenem were interpreted
      according to National Committee for Clinical Laboratory Standards guidelines. The
      susceptibility breakpoints for colistin and rifampicin were established as 4 mg/L
      and 2 mg/L, respectively, based on previous studies. Pseudomonas aeruginosa ATCC
      27853 and Escherichia coli ATCC 25922 were used as control strains. Testing
      against the P. aeruginosa strains revealed high MIC50 values for all the drugs
      except colistin. Doxycycline and colistin were both effective against the A.
      baumannii strains, with high susceptibility rates of 92% and 100%, respectively.
      Azithromycin had a high MIC50 value against these strains, whilst rifampicin had
      a moderate effect (susceptibility rate 64%). The combination of colistin and
      rifampicin was fully synergistic against four A. baumannii and two P. aeruginosa
      strains. Combinations of colistin with meropenem and of colistin with
      azithromycin each showed synergistic activity against three A. baumannii
      isolates, whilst the same combinations resulted in generally additive or
      indifferent effects against P. aeruginosa strains. The colistin and doxycycline
      combination was generally partially synergistic or additive against all the
      isolates. MDR strains of P. aeruginosa and A. baumannii, which cause nosocomial
      infections with an increasing ratio in recent years, have limited treatment
      options. According to our in vitro study results, non-traditional antibiotics
      such as doxycycline and colistin can be an alternative for the treatment of
      infections caused by these strains. Combinations of colistin with non-traditional
      antibiotics or meropenem could be promising alternatives for the treatment of
      infections due to MDR strains of A. baumannii and P. aeruginosa.

PMID- 16464563
TI  - AID in somatic hypermutation and class switch recombination.
AB  - Somatic hypermutation and class-switch-recombination are initiated by the
      deamination of deoxycytosine in DNA by activation-induced-deaminase, AID.
      Recently, there has been much research into how AID targets double-stranded DNA
      in sub-regions of Ig genes, the involvement of co-factors and posttranslational
      modifications in this process, the co-option of DNA 'repair' mechanisms and AID
      evolution.

PMID- 16464565
TI  - Therapeutic cancer vaccines.
AB  - The immunological bases of current approaches to therapeutic cancer vaccination
      (or 'vacci-treatment') have been established for a decade or longer. The new
      developments lie mostly in the lessons learnt from clinical testing of these
      approaches. Three lessons are particularly worthy of note. First, recently
      completed randomized Phase 3 trials suggest that vacci-treatment with autologous
      dendritic cells expressing prostatic acid phosphatase (for prostate cancer) or
      with autologous tumor-derived heat shock protein (gp96)-peptide complexes show
      promise in enhancing survival of cancer patients. These two approaches are
      undergoing further randomized clinical testing. Second, immunological monitoring
      of many clinical trials has failed to identify a surrogate marker for clinical
      outcomes. Finally, an increasing volume of literature suggests that protective
      immunity to human cancers is elicited by the mutated antigenic repertoire unique
      to each cancer.

PMID- 16464564
TI  - Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
AB  - Cytotoxic T lymphocyte antigen-4 has become recognized as one of the key negative
      regulators of adaptive immune responses, having a central role in the maintenance
      of peripheral tolerance and in shaping the repertoire of emergent T cell
      responses. Concurrent recognition of the potential importance of inhibitory
      immune regulators in limiting antitumor responses, either as a result of chronic
      antigenic stimulation or the self-nature of many tumor-selective target antigens,
      has led to the development of cytotoxic T lymphocyte antigen-4-blocking
      antibodies as therapeutic anticancer agents. Following extensive preclinical
      modeling, these agents have entered clinical trials, where they are showing
      encouraging activity in heavily pretreated patients with advanced-stage disease,
      particularly with melanoma or renal carcinoma. Finding ways to dissociate
      antitumor activity from adverse immune events should enable actualization of
      their therapeutic potential in the coming years.

PMID- 16464566
TI  - Transcription factors drive B cell development.
AB  - Transcription factors including PU.1, E2A and early B cell factor (EBF) are
      essential for the earliest stages of B lymphocyte development. Recent advances
      suggest that, although PU.1 initiates events leading to B lymphopoiesis, it might
      be dispensable at later stages of development. E2A proteins are also crucial for
      B cell lineage determination, as shown by the pluripotency of E2A-deficient
      progenitors. Both PU.1 and E2A are required for expression of EBF. EBF activates
      the early program of genes unique to B cells, including the lineage commitment
      factor Pax5. EBF also facilitates the function of Pax5 by mediating epigenetic
      changes necessary for the function of Pax5 at gene targets. Together, these
      proteins function in a hierarchy of factors that orchestrates B cell development.

PMID- 16464567
TI  - Immune regulation in tumor-bearing hosts.
AB  - A wealth of data indicates that tumor immunity directed against a wide variety of
      malignancies is suppressed in cancer patients. Recent studies have explored the
      role of 'natural' CD4(+)CD25(+) regulatory T cells (Tregs) in the suppression of
      tumor immunity in cancer patients. It is now clear, using multiple phenotypic and
      functional criteria, that the frequency of Tregs is increased in the peripheral
      blood of cancer patients as well as within the tumor microenvironment. Human
      Tregs with specificity for tumor-associated antigens have recently been
      identified, and murine studies have demonstrated that vaccination with tumor
      associated antigens can expand Tregs, posing a challenge to cancer vaccine
      strategies. However, a variety of approaches, including depletion of Tregs or
      modulation of their activity in vivo, might soon enhance the efficacy of existing
      cancer vaccines directed against a variety of malignancies.

PMID- 16464568
TI  - Lysine methylation and 'signaling memory'.
AB  - A combination of various post-translational modifications regulates the formation
      of signaling networks in both the nucleus and the cytosol. Of these, lysine
      methylation provides a relatively stable marker on histones and contributes to
      the formation of a distinct pattern of histone-dependent gene regulation
      ('transcriptional memory'). Thus far, lysine methylation was considered to be
      nucleus specific; however, recent findings indicate that lysine methylation
      contributes to receptor-mediated signal transduction in the cytosol.

PMID- 16464569
TI  - SU-8 based continuous-flow RT-PCR bio-chips under high-precision temperature
      control.
AB  - Being beneficial from dramatic progress in bio-chemical and micro-electro
      mechanical technologies, DNA manipulation devices can be miniaturized to expedite
      amplification processing for virus detection. Polymerase chain reaction (PCR) and
      reverse transcription polymerase chain reaction (RT-PCR) are two typical examples
      of them. In this report, a micro-RT-PCR (microRT-PCR) chip is designed to
      quantitatively detect tumor viruses. Test sample reservoirs, RT-PCR meanders, and
      capillary electrophoresis are integrated on a SU-8 based monolithic chip. A high
      precision temperature control module is well developed by embedding signal
      amplification circuits and an Intel 8051 microprocessor. The integrated system
      exhibits high efficacy for heat transfer, exemption of fluid flow clogging and
      superior sensitivity to precisely control the required reaction temperatures in
      all heated zones of microRT-PCR unit. Intensive simulations and experiments are
      presented to verify the validity of the fabricated bio-chip.

PMID- 16464570
TI  - High speed detection of circulating tumor cells.
AB  - Epithelial tumor cells circulate in peripheral blood at ultra-low concentrations
      in cancer patients. We have developed an instrument capable of rapid and accurate
      detection of rare cells in circulation utilizing fiber-optic array scanning
      technology (FAST). The FAST cytometer can locate immunofluorescently labeled rare
      cells on glass substrates at scan rates 500 times faster than conventional
      automated digital microscopy. These high scan rates are achieved by collecting
      fluorescent emissions using a fiber bundle with a large (50 mm) field of view.
      Very high scan rates make possible the ability to detect rare events without the
      requirement for an enrichment step. The FAST cytometer was used to detect, image
      and re-image circulating tumor cells in peripheral blood of breast cancer
      patients. This technology has the potential to serve as a clinically useful point
      of-care diagnostic and a prognostic tool for cancer clinicians. The use of a
      fixed substrate permits the re-identification and re-staining of cells allowing
      for additional morphologic and biologic information to be obtained from
      previously collected and identified cells.

PMID- 16464572
TI  - Hormone replacement therapy is more prevalent among Jewish BRCA1/2 mutation
      carriers.
AB  - The aim of this study was to compare reproductive factors, use of oral
      contraceptives (OC) and hormone replacement therapy (HRT) in consecutive Jewish
      Ashkenazi breast cancer patients, with and without BRCA1/BRCA2 mutations. Jewish
      Israeli women with breast cancer (n=385) were genotyped for the three predominant
      Jewish mutations in BRCA1 and BRCA2, and data on reproductive factors, OC and HRT
      use, were analyzed using logistic regression analyses. Overall, 28/385 (7.3%) of
      participants were mutation carriers, the majority of whom were Ashkenazi (n=22;
      78.6%) and were diagnosed with breast cancer at or under age 49 years (n=18;
      64.3%). Mutation carriers were more likely than non-carriers to ever use OC
      (39.3% vs. 20.2%; P=0.053), HRT (35.7% vs. 13.7%; P=0.007), and have first
      menarche at or below 12 years of age (71.4% vs. 40.6%; P=0.03). Multivariate
      analysis showed that Ashkenazi women diagnosed with breast cancer under 40 years
      of age, with a family history of breast/ovarian cancer, who ever used HRT were
      more likely to be mutation carriers. This study has shown that HRT use is more
      prevalent among Jewish Ashkenazi mutation carriers, but its role in modifying
      breast cancer risk in mutation carriers remains unknown.

PMID- 16464571
TI  - The association between Akt activation and resistance to hormone therapy in
      metastatic breast cancer.
AB  - In this retrospective study, the relationship between Akt activation and the
      efficacy of endocrine therapy for metastatic breast cancer was investigated.
      Thirty-six metastatic breast cancer patients, treated with endocrine therapy,
      were evaluated for the activation of Akt by an immunohistochemical assessment of
      the expression of phosphorylated Akt at Ser 473 (pAkt). The relationship between
      the efficacy of endocrine therapy and Akt activation, HER2 status and hormone
      receptor expression was also investigated. Of these 36 cases, 12 cases (33.4%)
      were considered to show a positive pAkt expression. In the pAkt-positive
      patients, endocrine therapy demonstrated a worse efficacy than in pAkt-negative
      patients (P<0.01). pAkt positivity was also associated with a poorer objective
      response (P<0.05). The clinical benefit rate was lower in HER2 positive groups
      than in HER2 negative group (P<0.05). In addition, the clinical benefit was the
      smallest in both the HER2 and pAkt-positive patients (P<0.01). Regarding the
      endocrine agents, the clinical benefit of estrogen deprivation therapy with
      aromatase inhibitor or luteinising hormone-releasing hormone agosists was
      significantly lower in the pAkt-positive patients than that in the pAkt-negative
      ones (P<0.05). In addition, there was a tendency for clinical benefit of
      selective estrogen receptor modulator to be smaller in the pAkt-positive patients
      (P=0.09). These findings, therefore, suggest that Akt activation induces
      endocrine resistance in metastatic breast cancer, irrespective of the kind of
      endocrine agents that were administered. Our findings suggest that the activation
      of Akt in the downstream pathway of HER2 plays an important role in the
      resistance to endocrine therapy for breast cancer. Although our study was small
      in scope and retrospective in design, our findings suggest that pAkt may be a
      useful predictor of resistance to endocrine therapy for breast cancer, while also
      suggesting that the inhibition of Akt may increase the efficacy of endocrine
      therapy.

PMID- 16464574
TI  - Synthesis of pyrazinamide Mannich bases and its antitubercular properties.
AB  - A series of pyrazinamide (PAZ) Mannich bases has been synthesized by reacting
      PAZ, formaldehyde, and various substituted piperazines using microwave
      irradiation with the yield ranging from 46% to 86%. The synthesized compounds
      were evaluated for antimycobacterial activity in vitro and in vivo against
      Mycobacterium tuberculosis H37Rv (MTB). Among the synthesized compounds, 1
      cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-4-((pyrazine-2
      carboxamido)methyl)piperazin-1-yl)-4-oxoquinoline-3-carboxylic acid (17) was
      found to be the most active compound in vitro with MIC of 0.39 and 0.2 microg/mL
      against MTB and multidrug-resistant MTB, respectively. In the in vivo animal
      model 17 decreased the bacterial load in lung and spleen tissues with 1.86 and
      1.66-log10 protections, respectively.

PMID- 16464573
TI  - Estrogen induces death of tamoxifen-resistant MCF-7 cells: contrasting effect of
      the estrogen receptor downregulator fulvestrant.
AB  - A common problem in breast cancer therapy is resistance to the antiestrogen
      tamoxifen. However, tamoxifen-resistant breast tumors can still respond to other
      hormonal therapies. In animal models of tamoxifen-resistant breast cancer cells,
      physiological levels of estrogen can induce tumor regression. Recently, the
      estrogen receptor downregulator fulvestrant was shown to promote tumor growth of
      tamoxifen-resistant cells when added in combination with physiological levels of
      estrogen. Here, we show, using a cell culture model, that continuous exposure of
      tamoxifen-resistant cells to physiological levels of estrogen leads to cell
      death. Addition of the estrogen receptor downregulator fulvestrant prevents
      estrogen-induced death in a dose-dependent manner. Our data indicate that
      endogenous levels of estrogen affect the response of tamoxifen-resistant cells to
      fulvestrant. These results suggest that failure of fulvestrant to inhibit tumor
      growth in some tamoxifen-resistant patients may be due to endogenous estrogen
      levels. Moreover, these studies support short-term treatment with estrogen as a
      second-line hormonal therapy for tamoxifen-resistant breast cancer.

PMID- 16464575
TI  - Synthesis of fluorescent derivatives of wortmannin and demethoxyviridin as probes
      for phosphatidylinositol 3-kinase.
AB  - Fluorescent analogs were synthesized of the potent PI 3-kinase inhibitors,
      wortmannin and demethoxyviridin. The esterification of 11-deacetylwortmannin, 17
      hydroxywortmannin, and demethoxyviridin with the fluorescent carboxylic acids NBD
      sarcosine and 7-dimethylaminocoumarin-4-acetic acid generated six novel
      fluorescent esters. Potent inhibition of PI 3-kinase-alpha was observed for the
      derivatives of 11-desacetylwortmannin and demethoxyviridin.

PMID- 16464576
TI  - A new class of bradykinin 1 receptor antagonists containing the piperidine acetic
      acid tetralin core.
AB  - The bradykinin 1 (B1) receptor is upregulated during times of inflammation and is
      important for maintaining inflamed and chronic pain states. Blocking this
      receptor has been shown to reverse and/or ameliorate pain and inflammation in
      animal models. In this report, we describe a new class of B1 receptor antagonists
      that contain the piperidine acetic acid tetralin core. A structure-activity
      relationship for these analogs is described in this paper. The most potent
      compounds from this class have IC50s<20 nM in a B1 receptor functional assay. One
      of these compounds, 13g, shows modest oral bioavailability in rats.

PMID- 16464577
TI  - Synthesis and ocular effects of imidazole nitrolic acid and amidoxime esters.
AB  - Esters of 1-(H)-imidazole-5-nitrolic acid and 1-methyl-imidazole-5-carboxamide
      oxime were prepared to study the effect of esterification on the ocular effects
      of these compounds. Esterifications were performed with acid chloride. Acid
      chloride also reacts with the ring nitrogen of 1-(H)-imidazole-5-nitrolic acid,
      but the desired esters could be selectively prepared by adjustment of the
      reaction conditions. Esterification led to loss of the ocular effects exhibited
      by the parent compounds.

PMID- 16464578
TI  - Design, synthesis, and biological evaluations of novel oxindoles as HIV-1 non
      nucleoside reverse transcriptase inhibitors. Part 2.
AB  - A series of heterocycle-containing oxindoles was synthesized and their HIV
      antiviral activities were assessed. Some of these analogs exhibited potent
      inhibitory activities against both wild-type virus and a number of drug-resistant
      mutant viruses. In addition, oxindole 9z also showed promising pharmacokinetics.

PMID- 16464579
TI  - Substituted coumarins as potent 5-lipoxygenase inhibitors.
AB  - Leukotriene biosynthesis inhibitors have potential as therapeutic agents for
      asthma and inflammatory diseases. A novel series of substituted coumarin
      derivatives has been synthesized and the structure-activity relationship was
      evaluated with respect to their ability to inhibit the formation of leukotrienes
      via the human 5-lipoxygenase enzyme.

PMID- 16464580
TI  - A practical and green approach towards synthesis of dihydropyrimidinones: using
      heteropoly acids as efficient catalysts.
AB  - A simple and green chemistry procedure for the synthesis of dihydropyrimidinones
      using heteropoly acid mediated cyclocondensation reaction is described. This
      method provides an efficient and much improved modification of the original
      Biginelli reaction reported in 1893, in terms of high yields, and short reaction
      times. It has the ability to allow a wide variety of substitutions in all three
      components.

PMID- 16464581
TI  - The synthesis of highly potent, selective, and water-soluble agonists at the
      human adenosine A3 receptor.
AB  - Using a combination of parallel and directed synthesis, the discovery of a highly
      potent and selective series of adenosine A3 agonists was achieved. High aqueous
      solubility, required for the intended parenteral route of administration, was
      achieved by the presence of one or two basic amine functional groups.

PMID- 16464582
TI  - Matrix compare analysis discriminates subtle structural differences in a family
      of novel antiproliferative agents, diaryl-3-hydroxy-2,3,3a,10a
      tetrahydrobenzo[b]cycylopenta[e]azepine-4,10(1H,5H)-diones.
AB  - A diastereoselective synthesis of diaryl-3-hydroxy-2,3,3a,10a
      tetrahydrobenzo[b]cycylopenta[e]azepine-4,10(1H,5H)-diones is described employing
      a tandem Michael-aldol addition as key step. The novel compounds exhibit
      antiproliferative activity in a panel of in vitro cultivated cancer cell lines.
      The bioinformatic tool COMPARE was able to discriminate between two closely
      related subgroups of the title compounds, namely 1,3- and 2,3-disubstituted
      derivatives.

PMID- 16464583
TI  - N-thiolated 2-oxazolidinones: a new family of antibacterial agents for
      methicillin-resistant Staphylococcus aureus and Bacillus anthracis.
AB  - In this report, we describe a new family of N-thiolated 2-oxazolidinones having
      antibacterial activity against methicillin-resistant Staphylococcus aureus and
      Bacillus anthracis. The effect of ring substituents and stereochemistry on
      antibacterial activity of these oxazolidinones closely parallels that previously
      reported for N-thiolated beta-lactam antibiotics.

PMID- 16464584
TI  - The spermicidal and antitrichomonas activities of SSRI antidepressants.
AB  - The study investigated spermicidal and antitrichomonas activities of selective
      serotonin reuptake inhibitor (SSRI) antidepressants with a view to generate new
      lead for development of dual-function spermicidal microbicides, which is an
      urgent global need. Fluoxetine, Sertraline, and Fluvoxamine exhibited both
      spermicidal and anti-STI (antitrichomonas) activities in vitro, whereas
      Paroxetine and Citalopram showed only the spermicidal activity. Fluoxetine
      exhibited better activity profile than the other antidepressant drugs with its
      spermicidal and antitrichomonas activities being comparable to that of the OTC
      contraceptive Nonoxynol-9. The non-detergent nature of Fluoxetine and a much
      lower spermicidal ED50 value (than N-9) may add considerably to its merit as a
      candidate for microbicidal contraceptive. Thus, the antidepressants exhibiting
      both spermicidal and antitrichomonas activities might provide useful lead for the
      development of novel, dual-function spermicidal contraceptives.

PMID- 16464585
TI  - Structure-activity relationship study between Ornithyl-Proline and Lysyl-Proline
      based tripeptidomimics as angiotensin-converting enzyme inhibitors.
AB  - A designed library of tripeptidomimics of Ornithyl-Proline (Orn-Pro) and Lysyl
      Proline (Lys-Pro) conjugated with various unnatural amino acids and carboxylic
      acid derived heterocyclics was synthesized and screened for possible inhibitors
      of angiotensin-converting enzyme (ACE). Among the tripeptidomimics 10[MTP-Orn
      Pro], 11[HTP-Orn-Pro], 14[TA-Orn-Pro] and 20[BPA-Orn-Pro] showed prominent
      inhibition with IC50 values in micromolar concentrations. Structure-activity
      relationship study indicated that C3 side chain of Orn as compared to C4 side
      chain of Lys at P1' position was better suited to inhibit ACE, with propionic
      acid (C3) derived heterocyclics and unnatural amino acids.

PMID- 16464586
TI  - Studies on synthesis and evaluation of quantitative structure-activity
      relationship of 10-methyl-6-oxo-5-arylazo-6,7-dihydro-5H-[1,3]azaphospholo[1,5
      d][1,4]benzodiazepin-2-phospha-3-ethoxycarbonyl-1-phosphorus dichlorides.
AB  - A new series of 10-methyl-6-oxo-5-arylazo-6,7-dihydro-5H-[1,3]azaphospholo[1,5
      d][1,4]benzodiazepin-2-phospha-3-ethoxycarbonyl-1-phosphorus dichlorides 11a-p
      has been synthesized and evaluated as antimicrobial agents. Structures of all the
      synthesized compounds were established on the basis of elemental analysis and
      spectroscopic data. Quantitative structure-activity relationship (QSAR)
      investigations were applied to find out the correlation between the
      experimentally evaluated activity with various parameters of the compounds
      studied. QSAR equations showed that the molecular refractivity correlates
      significantly with the antimicrobial activity.

PMID- 16464587
TI  - Antibacterial activity of (-)-deoxypseudophrynaminol versus its racemate and
      derivatives.
AB  - (-)-Deoxypseudophrynaminol 1 possesses 43-fold greater antibacterial potency than
      the racemate toward Staphylococcus aureus, indicating that the (-)-enantiomer is
      the biologically active isomer in this assay. Comparison of the percent growth
      inhibition by derivatives of 1 indicates that prenylation of N8 and replacement
      of N1-methyl by methyl carbamate are detrimental to antibacterial potency. (-)-1
      is a promising lead structure for the development of the novel
      hexahydropyrrolo[2,3-b]indole class of antibacterial agents.

PMID- 16464588
TI  - Synthesis and SAR of heteroaryl-phenyl-substituted pyrazole derivatives as highly
      selective and potent canine COX-2 inhibitors.
AB  - The discovery of heteroaryl-phenyl-substituted pyrazole derivatives as canine
      selective COX-2 inhibitors is described. Structure-activity relationship (SAR)
      studies of this class of compounds led to the identification of compound 1 which
      demonstrated a canine whole blood COX-2 inhibitory IC50 of 12 nM and selectivity
      ratio of COX-1/COX-2 greater than 4000-fold.

PMID- 16464589
TI  - Preparation and in vitro photodynamic activities of novel axially substituted
      silicon (IV) phthalocyanines and their bovine serum albumin conjugates.
AB  - Two novel axially substituted phthalocyanines, namely bis(4-(4
      acetylpiperazine)phenoxy)phthalocyaninatosilicon (IV) (1) and its N-methylated
      derivative 2, have been synthesized. The dicationic phthalocyanine 2 is non
      aggregated in water and exhibits good photophysical properties. The non-covalent
      BSA conjugates of these compounds have also been prepared. Compound 2 and the
      conjugate 2-BSA show extremely high photodynamic activities toward B16 melanoma
      cancer cell lines. The corresponding 50% growth-inhibitory (IC50) ratios are 33
      and 38 nM, respectively.

PMID- 16464590
TI  - Radanamycin, a macrocyclic chimera of radicicol and geldanamycin.
AB  - Radicicol and geldanamycin are potent inhibitors of the Hsp90 protein folding
      machinery, which is an emerging target for the development of cancer
      chemotherapeutics. However, radicicol is inactive in vivo and geldanamycin
      suffers from its redox-active behavior that produces toxicity unrelated to Hsp90
      inhibition. It was proposed that a chimeric molecule containing the resorcinol
      ring of radicicol and the quinone of geldanamycin could provide an opportunity to
      elucidate structure-activity relationships for both natural products and serve as
      a starting point for the development of more potent inhibitors. Synthesis of the
      macrocyclic chimera named radanamycin is reported along with the biological
      activity exhibited by this compound in MCF-7 breast cancer cells.

PMID- 16464592
TI  - Methylated beta-cyclodextrin as P-gp modulators for deliverance of doxorubicin
      across an in vitro model of blood-brain barrier.
AB  - Co-incubations of various beta-cyclodextrins and doxorubicin have been evaluated
      on an in vitro model of blood-brain barrier in order to increase the delivery of
      this P-gp substrate to the brain. Among these cyclodextrins used, the Rame-beta
      cyclodextrin and Crysme-beta-cyclodextrin increased the transport by a factor of
      2 and 3.7, respectively. This increase was attributed to the cholesterol
      extraction property of these cyclodextrins from brain capillary endothelial cells
      leading to a modulation of the P-gp activity.

PMID- 16464591
TI  - Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents.
AB  - Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of
      Eimeria tenella cGMP-dependent protein kinase activity reported to date and are
      efficacious in the in vivo antiparasitic assay when administered to chickens at
      12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the
      Ames microbial mutagenesis assay which precludes them from further development as
      antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity
      studies.

PMID- 16464593
TI  - Why does A&E attract newly qualified registered nurses?
AB  - Workforce planning is a particular buzzword that nurse managers must grapple with
      and now must understand. They must develop strategies to ensure the life and
      growth of a department while incorporating numerous government targets to ensure
      the service reaches quality, achieves and meets predetermined goals. To do all
      this that manager needs a workforce. The recruitment of nursing staff to a
      specialist area such as Accident & Emergency (A&E) requires a level of creativity
      and sustained effort. Newly qualified registered nurse working in A&E have, in
      the past, been considered to be an unusual group of staff to apply to work in
      A&E. However, many health service managers receive applications from staff in
      this category and are often encouraged to recruit newly qualified registered
      nurse's rather than pay for agency workers. Using a qualitative approach this
      paper explores the key reasons why newly qualified registered nurses choose to
      work in an Accident & Emergency environment. Data was collected from a sample of
      25 newly qualified registered nurses and analysed thematically. Five themes are
      presented: challenge, teamwork, diversity, support, and learning. These themes
      have implications for Accident and Emergency units and human resource and
      workforce planning departments.

PMID- 16464594
TI  - Field of view and base of support width influence postural responses to visual
      stimuli during quiet stance.
AB  - We explored the destabilizing effect of visual field motion as the base of
      support (BOS) and the field of view (FOV) were narrowed. Visual field motion was
      achieved using an immersive virtual environment (scene) that moved realistically
      with head motion (natural motion) and translated sinusoidally at 0.1Hz in the
      fore-aft direction (augmented motion). Natural motion was presented in stereo
      while augmented motion was presented in both stereo and non-stereo. Subjects
      viewed scene motion under wide (90 degrees and 55 degrees in the horizontal and
      vertical directions) and narrow (25 degrees in both directions) FOV conditions
      while standing flatfooted (100% BOS) and on two blocks (45% and 35% BOS). Head
      and whole body center of mass (COM) and ankle angle root mean square (RMS) were
      determined as were head, whole body, and shank COM FFTs. During natural motion,
      the primary effect emerged in the head RMS which was significantly smaller with a
      35% BOS and the wide FOV compared to the narrow FOV. However, the primary effect
      of augmented motion emerged in the power analysis of head and whole body COM
      which significantly increased with the wide FOV for a 35% BOS compared to 100%
      BOS. Statistical analysis indicated an effect of BOS on depth perception for head
      and whole body RMS; however, post hoc comparisons revealed no significant
      differences between stereo and non-stereo augmented motion. We conclude that
      reducing the BOS increased reliance on peripheral visual information to stabilize
      the head in space even when the augmented visual motion promoted postural
      instability.

PMID- 16464595
TI  - Age associated differences in postural equilibrium control: a comparison between
      EQscore and minimum time to contact (TTC(min)).
AB  - Increased postural instability and the subsequent elevation in fall incidence
      with increasing age are important contributors for hip fractures and developing
      frailty. When testing for such instability, most studies characterize balance in
      terms of center-of-mass (COM) deviation from a finite point, the "equilibrium
      point", located at the center of a subject's stance. For example, the clinically
      accepted equilibrium score (EQscore) represents instability as the maximum peak
      to-peak sway about the "equilibrium point". An alternative theory views balance
      as being controlled within a "stability margin" in which all corrective actions
      are based on the time to contact (TTC) of the body's COM with that margin. This
      study examines the differences offered by evaluating balance control using the
      EQscore and TTC approach across several age groups and sessions. Consenting
      subjects from the Baltimore Longitudinal Study of Aging were recruited (N=155)
      from each age decade (20s-80s) who were generally healthy and free from
      neurological diagnoses. Results showed TTC tests detected significant variations
      in eyes open versus eyes closed testing that were unpredictable by EQscore.
      Further, TTC produced differences in age-related stability threats not seen using
      EQscore. The TTC data also provided a discriminating difference between subjects
      who fell in the difficult tests and those who maintained posture. Overall, these
      data suggest EQscore might not sufficiently account for dynamic control
      components the body may be using to maintain balance. TTC may offer a more
      accurate estimate of postural stability (functional ability) than EQscore based
      on its inclusion of a velocity component to detect dynamic changes.

PMID- 16464596
TI  - A method for manipulating a movable platform's axes of rotation: a novel use of
      the CAREN system.
AB  - The functionality of movable platforms used in human balance studies is limited
      as they allow rotations around pre-defined axes, which typically run close to the
      platform's surface and so cannot be used to directly investigate control
      mechanisms of proximal joints. A new six degrees of freedom platform (CAREN,
      Motek, Amsterdam) is now available which in principle could be programmed to
      rotate around any axis of rotation. The location of the default axes of rotation
      for this device are not documented and the algorithm to move the axes has not yet
      been defined. The purpose of this study was to (1) locate the platform's default
      axes of rotation, (2) implement an algorithm for relocating its axes of rotation
      and (3) evaluate the algorithm. A simplified method was developed to locate the
      bounding rectangles within which the default axes of rotations were located. The
      three axes of rotation were found to be at x=1.13+/-0.69 mm, z=-204.22+/-0.63 mm
      in the roll plane, y=-2.67+/-0.59 mm, z=-211.38+/-0.63 mm in the pitch plane and
      x=0.43+/-0.70 mm, y=-4.72+/-0.65 mm in the yaw plane (X: left, Y: rear, Z: up),
      relative to the centre of its surface, with the maximum bounding rectangle of
      dimensions 2.50mm by 2.42 mm. Relocation of the platform's axes of rotation was
      achieved by the use of compensatory corrections, which were determined using a
      translation algorithm. Evaluation of the algorithm involved pitching the platform
      around three newly defined axes in the sagittal plane, representing the ankle,
      knee and hip joints. The platform was able to rotate around the new axes while
      keeping the instantaneous axes of rotation within bounding rectangles of 1.87 mm
      x 0.81 mm (ankle), 3.04 mm x 1.23 mm (knee), 3.14 mm x 1.63 mm (hip). The ability
      to overcome the limitation of other moveable platforms makes the CAREN system a
      valuable tool in research on the role of individual joints in balance.

PMID- 16464597
TI  - New sesquiterpene from Vietnamese agarwood and its induction effect on brain
      derived neurotrophic factor mRNA expression in vitro.
AB  - Agarwood, one of the valuable non-timber products in tropical forest, is a
      fragrant wood, whose ethereal fragrance has been prized in Asia for incense in
      ceremony, as well as sedatives in traditional medicine. We separated the 70% EtOH
      extract of Vietnamese agarwood, which showed significant induction effect on
      brain-derived neurotrophic factor (BDNF) mRNA expression in rat cultured neuronal
      cells, to isolate a new compound and a 2-(2-phenylethyl)chromone derivative. The
      new compound was determined to be a spirovetivane-type sesquiterpene, (4R,5R,7R)
      1(10)-spirovetiven-11-ol-2-one, by spectroscopic data and showed induction effect
      of BDNF mRNA.

PMID- 16464598
TI  - Binding of oxalyl derivatives of beta-d-glucopyranosylamine to muscle glycogen
      phosphorylase b.
AB  - Five oxalyl derivatives of beta-d-glucopyranosylamine were synthesized as
      potential inhibitors of glycogen phosphorylase (GP). The compounds 1-4 were
      competitive inhibitors of rabbit muscle GPb (with respect to alpha-d-glucose-1
      phosphate) with K(i) values of 0.2-1.4 mM, while compound 5 was not effective up
      to a concentration of 10 mM. In order to elucidate the structural basis of their
      inhibition, we analysed the structures of compounds 1-4 in complex with GPb at
      1.93-1.96 Angstrom resolution. The complex structures reveal that the inhibitors
      can be accommodated at the catalytic site at approximately the same position as
      alpha-d-glucose and stabilize the T-state conformation of the 280 s loop by
      making several favourable contacts to Asp283 and Asn284 of this loop. Comparison
      with the lead compound N-acetyl-beta-d-glucopyranosylamine (6) shows that the
      hydrogen bonding interaction of the amide nitrogen with the main-chain carbonyl
      oxygen of His377 is not present in these complexes. The differences observed in
      the K(i) values of the four analogues can be interpreted in terms of subtle
      conformational changes of protein residues and shifts of water molecules in the
      vicinity of the catalytic site, variations in van der Waals interactions,
      conformational entropy and desolvation effects.

PMID- 16464599
TI  - Direct assay for alpha-amylase using fluorophore-modified cyclodextrins.
AB  - A simple assay method for alpha-amylase was developed based on fluorophore
      modified cyclodextrins (CDs). Four kinds of CD derivatives bearing a 4-amino-7
      nitrobenz-2-oxa-1,3-diazole (NBD-amine) moiety were prepared as artificial
      substrates for the assay method. The fluorescence intensity of all the NBD-amine
      modified CDs decreased upon addition of Aspergillus oryzae alpha-amylase,
      indicating a reduction in hydrophobicity near the NBD-amine moiety induced by
      hydrolysis of the CD ring. NC4gammaCD, having a gamma-CD and an amino
      tetramethylene spacer, was the most sensitive substrate for the alpha-amylase
      assay. The initial rate of hydrolysis of NC4gammaCD displayed a liner correlation
      to the concentration of the alpha-amylase. NC4gammaCD was sensitive to the alpha
      amylase but was not sensitive to guest compounds that were accommodated by the
      native CDs.

PMID- 16464600
TI  - An unusual functional group interaction and its potential to reproduce steric and
      electrostatic features of the transition states of peptidolysis.
AB  - The donor-acceptor interaction between a tertiary amine and an aldehyde, first
      observed among a select class of alkaloids, was deliberately established in a
      peptidomimetic (1a-c) to mimic features of the two principal transition states of
      peptide hydrolysis. Compounds 1a-c show preferential adoption in methanol and
      water of a 'folded' conformation displaying the interaction. Proportions of the
      folded form in MeOH range from 45% to 70% and can reach 84% in buffer.
      Significantly, three tendencies for the folded/unfolded equilibrium are observed:
      increasing solubility and polarity of the medium and decreasing temperature
      results in a higher extent of folding. In the absence of any parameter set
      available for this weak bond, no modeling studies were conducted to aid in the
      design of 1a-c. The successful straightforward synthesis of 1 and its folding and
      inhibition results with HIV-1 peptidase using FRET technology encourage studies
      to further pre-organize candidate molecules and to screen the structure space by
      modeling and parallel combinatorial chemistry.

PMID- 16464601
TI  - Synthesis, anticonvulsant, and anti-inflammatory evaluation of some new
      benzotriazole and benzofuran-based heterocycles.
AB  - Treatment of 2-bromoacetylbenzofuran with 1H-benzotriazole afforded 1-(benzofuran
      2-yl)-2-(benzotriazol-1-yl)ethanone which reacted with phenylisothiocyanate to
      give the corresponding thioacetanilide derivatives. Treatment of the latter
      ethanone and thioacetanilide derivatives with hydrazonoyl chlorides afforded the
      corresponding pyrazole and 1,3,4-thiadiazole derivatives. The thioacetanilide
      derivative reacted with alpha-haloketones and alpha-halodiketones to afford
      thiophene and thiazole derivatives, respectively. The newly synthesized compounds
      were found to possess anticonvulsant and anti-inflammatory activities with the
      same mechanism of action of selective COX-2 inhibitors.

PMID- 16464602
TI  - Solvent free microwave synthesis and evaluation of antimicrobial activity of
      pyrimido[4,5-b]- and pyrazolo[3,4-b]quinolines.
AB  - A series of 2-oxopyrimido[4,5-b]-, 2-thio[4,5-b]-, 1-(p-tosyl)pyrazolo[3,4-b]-
      and 1-(2',4'-dinitrophenyl)pyrazolo[3,4-b]-quinolines have been synthesized in
      good to excellent yields by environmentally benign solvent free microwave-induced
      techniques involving the condensation of 2-chloro-3-formylquinolines with urea,
      thiourea, p-toluenesulfonylhydrazide and 2,4-dinitrophenylhydrazine,
      respectively, using PTSA as a catalyst. All the synthesized compounds were
      evaluated for their antibacterial and antifungal activities. Most of the
      compounds showed the best activity against Escherichia coli and Pseudomonas
      aeruginosa.

PMID- 16464603
TI  - Relationship between the organization of the PS II super complex and the
      functions of the photosynthetic apparatus.
AB  - The chlorophyll fluorescence and the photosynthetic oxygen evolution (flash
      induced oxygen yield patterns and oxygen bursts under continuous irradiation)
      were investigated in the thylakoid membranes with different stoichiometry and
      organization of the chlorophyll-protein complexes. Data show that the alteration
      in the organization of the photosystem II (PS II) super complex, i.e. the amount
      and the organization of the light-harvesting chlorophyll a/b protein complex
      (LHCII), which strongly modifies the electric properties of the membranes,
      influences both the energy redistribution between the two photosystems and the
      oxygen production reaction. The decrease of surface electric parameters (charge
      density and dipole moments), associated with increased degree of LHCII
      oligomerization, correlates with the strong reduction of the energy transfer from
      PS II to PSI. In the studied pea thylakoid membranes (wild types Borec, Auralia
      and their mutants Coeruleovireus 2/16, Costata2/133, Chlorotica XV/1422) with
      enhanced degree of oligomerization of LHCII was observed: (i) an increase of the
      S(0) populations of PS II in darkness; (ii) an increase of the misses; (iii) an
      alteration of the decay kinetics of the oxygen bursts under continuous
      irradiation. There is a strict correlation between the degree of LHCII
      oligomerization in the investigated pea mutants and the ratio of functionally
      active PS II alpha to PS II beta centers, while in thylakoid membranes without
      oligomeric structure of LHCII (Chlorina f2 barley mutant) the PS II alpha centers
      are not registered.

PMID- 16464604
TI  - Effect of different salts and detergents on luciferin-luciferase luminescence of
      the enchytraeid Fridericia heliota.
AB  - The study addresses the effect produced by different inorganic salts and
      detergents (SDS, Triton X-100, the Tween series) on the ATP-dependent
      bioluminescent reaction catalyzed by the luciferase of the new earthworm species
      Fridericia heliota (Annelida: Clitellata: Oligochaeta: Enchytraeidae). It has
      been shown that the effect of divalent metal salts on luminescence is determined
      by the action of cations. Three of them - Mg(2+), Mn(2+) and Ca(2+) - can
      stimulate luciferase activity at concentrations varying within a wide range, and
      Mn(2+) can act as a 100%-effective substitute for Mg(2+) in F. heliota
      luminescence reaction in vitro. The inhibitory effect of monovalent metal salts
      on luminescence is largely determined by the action of the anion part of the
      molecule. The effectiveness of the inhibitory effect of anions increases in the
      following order: Cl(-)<CO(3)(-2) approximately SO(3)(-2) approximately Br(
      )<SO(4)(-2) approximately PO(4)(-3)<NO(3)(-)<I(-)<<Cr(2)O(7)(-2)<<Fe(CN)(6)(-3).
      Of the sodium salts, dodecyl sulfate, which is an anionic detergent, produces the
      strongest inhibitory effect on luciferase. On the contrary, nonionic detergents
      produce a stimulatory effect on the F. heliota luciferase. The action of the most
      effective of them - Triton X-100 - is determined by its ability to reduce the
      actual concentration of lipid inhibitors in the reaction mixture.

PMID- 16464605
TI  - A developmental switch induced by thyroid hormone: Xenopus laevis metamorphosis.
AB  - Thyroid hormone induces the complete metamorphosis of anuran tadpoles into
      juvenile frogs. Arguably, anuran metamorphosis is the most dramatic effect of a
      hormone in any vertebrate. Recent advances in pharmacology and molecular biology
      have made the study of this remarkable process in the frog Xenopus laevis
      attractive to developmental biologists and endocrinologists alike. In particular,
      the availability of a straightforward transgenesis assay and the near completion
      of the Xenopus tropicalis genome are enabling significant advances to be made in
      our understanding of the major remaining problems of metamorphosis: the
      extraordinary tissue specificity of responses, the precise timing of
      morphological changes, the degree of cell autonomy of hormone responses and
      developmental competence. We argue that X. laevis metamorphosis presents an
      exciting opportunity for understanding the role of thyroid hormone in vertebrate
      development.

PMID- 16464606
TI  - Algorithms for automatic interpretation of high resolution mass spectra.
AB  - Automated interpretation of high-resolution mass spectra in a reliable and
      efficient manner represents a highly challenging computational problem. This work
      aims at developing methods for reducing a high-resolution mass spectrum into its
      monoisotopic peak list, and automatically assigning observed masses to known
      fragment ion masses if the protein sequence is available. The methods are
      compiled into a suite of data reduction algorithms which is called MasSPIKE (Mass
      Spectrum Interpretation and Kernel Extraction). MasSPIKE includes modules for
      modeling noise across the spectrum, isotopic cluster identification, charge state
      determination, separation of overlapping isotopic distributions, picking isotopic
      peaks, aligning experimental and theoretical isotopic distributions for
      estimating a monoisotopic peak's location, generating the monoisotopic mass list,
      and assigning the observed monoisotopic masses to possible protein fragments. The
      method is tested against a complex top-down spectrum of bovine carbonic
      anhydrase. Results of each of the individual modules are compared with previously
      published work.

PMID- 16464607
TI  - Characterization of self-assembled supramolecular [Ga4L6] host-guest complexes by
      electrospray ionization mass spectrometry.
AB  - Self-assembled supramolecular host-guest complexes have been characterized by
      electrospray ionization mass spectrometry. The spectra obtained by use of a Q-TOF
      instrument equipped with a Z-spray ion source show primarily the 3- and 4- charge
      states of the assemblies. The assemblies have the general formula [guest subset
      Ga4L6]11- where L represents the chelating bidentate catechol ligand 1,5
      bis(2',3'-dihydroxy-benzamido)naphthalene and guests are tetramethyl ammonium
      (Me4N+), tetraethyl ammonium (Et4N+), tetra-n-propyl ammonium (Pr4N+) and
      decamethylcobaltocenium (Cp*2Co+) cations. For the first time, the mass spectrum
      of the empty assembly [Ga4L6]12- is reported. This article also reports that
      provided the electrospray ion source is capable of preserving noncovalent
      interactions, it is possible to observe host-guest complexes containing both weak
      binding guests as well as sterically demanding guests in the mass spectra. The
      present data suggest that electrospray mass spectrometry is a powerful tool for
      characterization of supramolecular host-guest complexes.

PMID- 16464609
TI  - Tr1 cells: from discovery to their clinical application.
AB  - Peripheral tolerance is mediated by multiple mechanisms such as anergy and/or
      active suppression of effector T cells by T regulatory (Tr) cells. Among the
      CD4(+) Tr cells, T regulatory type 1 cells (Tr1) have been shown to down-modulate
      immune responses through production of the immunosuppressive cytokines IL-10 and
      TGF-beta. Tr1 cells maintain peripheral tolerance, control autoimmunity, and
      prevent allograft rejection and graft versus host disease (GvHD). Cellular
      therapy with ex vivo generated Tr1 cells has been proven to be effective in
      several preclinical models of T cell-mediated pathologies and therefore,
      represents a promising approach for clinical application. This review will
      summarize the new findings on Tr1 cells, the recent development of methods for
      their ex vivo expansion, and their potential clinical relevance as cellular
      therapy.

PMID- 16464608
TI  - Powered by pairing: the surrogate light chain amplifies immunoglobulin heavy
      chain signaling and pre-selects the antibody repertoire.
AB  - Selective expansion of functional pre-B cells is accomplished by the assembly of
      a signaling-competent pre-B cell receptor (pre-BCR) consisting of immunoglobulin
      mu heavy chains (muHC), surrogate light chains (SLC) and Igalpha/Igbeta. Here, we
      review recent data showing that muHCs, in the absence of SLC, deliver autonomous
      differentiation signals. However, enhanced signaling necessary for pre-B cell
      expansion requires cross-linking of pre-BCRs via the non-immunoglobulin tail of
      SLC's subunit lambda5. We also discuss how SLC's ability to modulate the strength
      of pre-BCR signals is controlled by a muHC's idiotype and its affinity to the
      chaperone BiP. In this model, BiP in concert with SLC functions as a pre-selector
      of the antibody repertoire.

PMID- 16464610
TI  - Summary of recombinant human serum albumin development.
AB  - The methylotrophic yeast Pichia pastoris is well known as a host strain for the
      production of a variety of heterologous proteins. We have used P. pastoris for
      the production of recombinant human serum albumin (rHSA), for which we have
      developed efficient and specialized downstream processes. Results from structural
      analysis suggest that purified rHSA possesses an identical conformation to plasma
      derived human albumin (pdHA) and no difference from pdHA has been observed in neo
      antigenicity. Host-cell-derived impurities (i.e. Pichia yeast component, DNA and
      mannan) have been evaluated in the purification process as well as in the drug
      substance and relevant specifications established. The efficacy and safety of
      rHSA have been tested in clinical studies and no difference from pdHA has been
      found in comparative study. Such studies have confirmed rHSA to have high
      efficacy with little or no adverse reaction.

PMID- 16464611
TI  - Birth weights of black African babies of migrant and nonmigrant mothers compared
      with those of babies of European mothers in Portugal.
AB  - PURPOSE: The study aim is to investigate differences in birth weights between
      babies of foreign-born black African, Portugal-born black African, and Portugal
      born white mothers. METHODS: Hospital records for Amadora and Sintra from July
      2001 to June 2002 were collated and 2949 Portugal-born white, 461 Portugal-born
      black African, and 817 foreign-born black African live singleton babies were
      identified. The impact of biologic and social factors (infant sex, maternal age,
      parity, gestational age, and maternal smoking, education, and occupational class)
      and mode of delivery on birth weights was assessed by using multivariable
      regression models. RESULTS: African mothers were more likely to be of lower
      socioeconomic status than white Portuguese mothers, among whom rates of smoking
      were two to three times greater (21% among white Portuguese mothers). Small
      preterm babies comprised 1.5% of white Portuguese babies, 2.3% of babies of
      Portugal-born African mothers, and 3.9% of babies of foreign-born African mothers
      (p < 0.05 compared with white Portuguese babies). Compared with white Portuguese
      babies, mean birth weight of term babies, adjusted for sex, among Portugal-born
      African mothers was -24.6 g (95% confidence interval, -70.1-20.9), and among
      foreign-born African mothers, was +38.8 g (95% confidence interval, 2.9-74.8).
      Adjustment for parity, maternal age, and gestational age decreased the
      significant birth weight advantage of babies of foreign-born African mothers to
      +2.3 g (95% confidence interval, -31.9-36.5). Among nonsmokers, after adjusting
      for these factors, white Portuguese babies were heavier (40 g; p < 0.05) than
      babies of foreign-born African mothers, but among smokers, they were lighter (163
      g; p < 0.05). CONCLUSIONS: Compared with white Portuguese babies, mean birth
      weight of term babies of foreign-born African mothers was greater, and that of
      babies of Portugal-born African mothers was intermediate. These differences were
      related to a combination of biologic factors and smoking.

PMID- 16464612
TI  - Induction time for resistance to microsporidial gill disease caused by Loma
      salmonae following vaccination of rainbow trout (Oncorhynchus mykiss) with a
      spore-based vaccine.
AB  - Resistance to re-infection of rainbow trout to Loma salmonae, a microsporidian
      gill parasite has been previously documented and this study examined how rapidly
      this resistance develops. Naive rainbow trout were inoculated intraperitoneally
      (IP) with an inactivated spore-based vaccine and were then given an oral
      challenge with a high dose of L. salmonae spores at various weeks after being
      vaccinated. Non-vaccinated naive fish (exposed group) were challenged alongside
      of each group of vaccinated fish to ensure that the challenges were relatively
      standardised. In each group of fish, four weeks after the challenge, numbers of
      xenomas were counted on a gill arch for all fish. Vaccinated trout were
      completely resistant to a L. salmonae challenge six weeks after vaccination,
      although the onset of resistance began at approximately week 3, as observed with
      a reduction in the percent infected and xenoma intensity. The maximum percent
      infected for the vaccinated fish was 83% following a challenge two weeks
      following vaccination, whereas for the exposed group the maximum prevalence of
      100% was reached several times. With continued research, a spore-based vaccine
      for L. salmonae has the potential to become the first commercially available
      parasite vaccine for fish.

PMID- 16464613
TI  - Beta-2-microglobulin gene expression is maintained in rainbow trout and Atlantic
      salmon kept at low temperatures.
AB  - Finfish in the wild are regularly subjected to low temperatures, which have been
      shown to cause a loss of Major Histocompatibility receptor expression in common
      carp kept at 6 degrees C. This is similar to what was seen in a mammalian cell
      line cultured at 26 degrees C. Loss of expression of this critical viral
      recognition protein may provide one mechanism for the increased frequency of fish
      diseases at low temperatures. This report demonstrates that unlike carp and
      mammals, beta(2)m transcript levels in both rainbow trout and Atlantic salmon do
      not decrease after 10 days at temperatures as low as 2 degrees C. Reverse
      transcriptase (RT)-PCR indicated that transcript steady-state levels of trout
      beta(2)m were maintained in both tissues and peripheral blood leucocytes, whether
      freshly isolated or in primary culture. Polyclonal antibodies raised against a
      recombinant form of trout beta(2)m, demonstrated cross-reactivity to both rainbow
      trout and Atlantic salmon protein lysates. Use of these antibodies in western
      blot analyses indicated that cellular protein levels are also maintained at low
      temperatures in both species while qualitative epifluorescence analysis of
      freshly isolated peripheral blood leucocytes indicated persistent cell surface
      expression of trout beta(2)m even after 10 days at 2 degrees C. Rainbow trout and
      Atlantic salmon may therefore utilise an alternative mode of immune gene
      regulation than the common carp and mammals allowing them to maintain viral
      recognition machinery at low temperatures, possibly due to selection for survival
      in cold climates.

PMID- 16464614
TI  - Improved uptake of plant-derived LTB-linked proteins in carp gut and induction of
      specific humoral immune responses upon infeed delivery.
AB  - Oral vaccination of fish is an effortless and stress free immunisation method
      which can be used for almost any age. However, vaccination via the mucosal route
      does have disadvantages. For example, the vaccine may induce tolerance and has to
      be protected to escape digestion. Also the vaccine should be efficiently
      delivered to immune-competent cells in the gut or other lymphoid organs. In
      addition, it should be cost effective. Here we present a novel fish vaccination
      model using potato tubers as vaccine production and delivery system. The model
      vaccines discussed here include fusion proteins consisting of a gut adhesion
      molecule (LTB) and a viral peptide or green fluorescent protein (GFP) expressed
      in potato tubers. The adhesion molecule mediates binding to and uptake from the
      gut, whereas the viral peptide or GFP functions as model vaccine antigen
      provoking the induction of an immune response. We demonstrate that fusion to LTB
      facilitates an elevated uptake of the model vaccines in carp gut mucosa. The
      plant-derived fusion proteins also elicit a specific systemic humoral immune
      response upon oral application of crude tuber material incorporated into a
      standard dietary feed pellet. The data presented here show the promising
      potentials of the plant as a production system for oral vaccines in aquaculture
      and feed mediated immunisation of fish.

PMID- 16464615
TI  - Do school-age children remember or know the personal past?
AB  - The aim of this study was to examine developmental differences in
      autobiographical memory using a novel test that assesses its semantic and
      episodic subcomponents. Forty-two children aged 7-13 years were asked to recall
      semantic information and episodic events from three different time periods
      (current school year, last school year, and previous school years). For the
      recalls of all events, sense of remembering or sense of just knowing was measured
      via the Remember/Know paradigm. Age-related differences were observed for
      episodic autobiographical memory whereas semantic autobiographical memory was
      characterized by a relative developmental invariance. The increase with age was
      also found in the number of "Remember" responses and their justification in terms
      of the actual contextual information retrieved-factual, spatial, and, more
      especially, temporal details. These findings highlight developmental differences
      between the episodic and semantic subcomponents of autobiographical memory and
      support the view that mental 'time travel' through subjective time, which allows
      one to re-experience the past through self-awareness, is the last feature of
      autobiographical memory to become fully operational.

PMID- 16464616
TI  - Thought as action: inner speech, self-monitoring, and auditory verbal
      hallucinations.
AB  - Passivity experiences in schizophrenia are thought to be due to a failure in a
      neurocognitive action self-monitoring system (NASS). Drawing on the assumption
      that inner speech is a form of action, a recent model of auditory verbal
      hallucinations (AVHs) has proposed that AVHs can be explained by a failure in the
      NASS. In this article, we offer an alternative application of the NASS to AVHs,
      with separate mechanisms creating the emotion of self-as-agent and other-as
      agent. We defend the assumption that inner speech can be considered as a form of
      action, and show how a number of previous criticisms of applying the NASS to AVHs
      can be refuted. This is achieved in part through taking a Vygotskian
      developmental perspective on inner speech. It is suggested that more research
      into the nature and development of inner speech is needed to further our
      understanding of AVHs.

PMID- 16464617
TI  - Priming of semantic classifications by novel subliminal prime words.
AB  - Four experiments demonstrate category congruency priming by subliminal prime
      words that were never seen as targets in a valence-classification task
      (Experiments 1, 2, and 4) and a gender-classification task (Experiment 3). In
      Experiment 1, overlap in terms of word fragments of one or more letters between
      primes and targets of different valences was larger than between primes and
      targets of the same valence. In Experiments 2 and 3, the sets of prime words and
      target words were completely disjoint in terms of used letters. In Experiment 4,
      pictures served as targets. The observed subliminal priming effects for novel
      primes cannot be driven by partial analysis of primes at the word-fragment level;
      they suggest instead that primes were processed semantically as whole words
      contingent upon prime duration.

PMID- 16464618
TI  - The complete mitochondrial genomes of Schistosoma haematobium and Schistosoma
      spindale and the evolutionary history of mitochondrial genome changes among
      parasitic flatworms.
AB  - Complete mitochondrial genome sequences for the schistosomes Schistosoma
      haematobium and Schistosoma. spindale have been characterized. S. haematobium is
      the causative agent of urinary schistosomiasis in humans and S. spindale uses
      ruminants as its definitive host; both are transmitted by freshwater snail
      intermediate hosts. Results confirm a major gene order rearrangement among
      schistosomes in all traditional Schistosoma species groups other than Schistosoma
      japonicum; i.e., species groups S. mansoni, S. haematobium, and S. indicum. These
      data lend support to the 'out of Asia' (East and Southeast Asia) hypothesis for
      Schistosoma. The gene order change involves translocation of atp6-nad2-trnA and a
      rearrangement of nad3-nad1 relative to other parasitic flatworm mt genomes so far
      sequenced. Gene order and tRNA secondary structure changes (loss and acquisition
      of the DHU and/or TPsiC arms of trnC, trnF, and trnR) between mitochondrial
      genomes of these and other (digenean and cestode) flatworms were inferred by
      character mapping onto a phylogeny estimated from nuclear small subunit rRNA gene
      sequences of these same species, in order to find additional rare genomic changes
      suitable as synapomorphies. Denser and wider taxon sampling of mt genomes across
      the Platyhelminthes will validate these putative characters.

PMID- 16464619
TI  - Spatial learning and goldfish telencephalon NMDA receptors.
AB  - Recent results have demonstrated that the mammalian hippocampus and the dorso
      lateral telencephalon of ray-finned fishes share functional similarities in
      relation to spatial memory systems. In the present study, we investigated whether
      the physiological mechanisms of this hippocampus-dependent spatial memory system
      were also similar in mammals and ray-finned fishes, and therefore possibly
      conserved through evolution in vertebrates. In Experiment 1, we studied the
      effects of the intracranial administration of the noncompetitive NMDA receptor
      antagonist MK-801 during the acquisition of a spatial task. The results indicated
      dose-dependent drug-induced impairment of spatial memory. Experiment 2 evaluated
      if the MK-801 produced disruption of retrieval of a learned spatial response.
      Data showed that the administration of MK-801 did not impair the retrieval of the
      information previously stored. The last experiment analyzed the involvement of
      the telencephalic NMDA receptors in a spatial and in a cue task. Results showed a
      clear impairment in spatial learning but not in cue learning when NMDA receptors
      were blocked. As a whole, these results indicate that physiological mechanisms of
      this hippocampus-dependent system could be a general feature in vertebrate, and
      therefore phylogenetically conserved.

PMID- 16464620
TI  - Experimental study of aortic anastomosis using a circular stapling device in the
      porcine model.
AB  - OBJECTIVES: The aim of this study was to assess the strength (pressure
      resistance) and histological findings of aortic anastomoses performed using a
      circular stapling device. MATERIALS AND METHODS: A circular stapling device was
      used for anastomosing a porcine aorta and a Dacron graft. The maximum pressure
      resistance of the anastomotic site of a porcine aortic specimen and a Dacron
      graft was examined (n=10). A porcine aorta with Dacron graft was anastomosed to a
      beating heart, and pressure overload was induced by adrenaline (n=5). Specimens
      of the anastomotic sites were harvested after 14 days and examined
      histologically. RESULTS: The maximum pressure resistance of the anastomotic site
      was 427.3+/-34.4 (375-511) mmHg. No anastomotic sites leaked as a result of
      pressure overloading at 227.6+/-21.1 (201-260) mmHg. Histologically, good
      incorporation and cell coverage were observed, and the inner surfaces of the
      anastomotic sites were smooth and without stenoses. CONCLUSIONS: Aortic
      anastomosis using a circular stapling device is feasible and worthy of further
      investigation.

PMID- 16464621
TI  - Collagen-induced platelet activation.
AB  - Platelet collagen receptors, such as Gp VI, are attractive targets for
      antithrombotic therapy. In this paper, I discuss the current knowledge regarding
      collagen-platelet interactions, including the role of platelet receptors, the
      recognition of collagen by platelets, the effect of the interaction on platelet
      activation and thrombosis and the effect of collagen structure on the platelet
      interaction, and highlight the areas in which additional information is required
      to pursue the goal of antithrombotic therapy, using the collagen-platelet
      interaction as the site of intervention. Understanding the detail of the receptor
      recognition motifs within collagen not only may reveal new antithrombotic targets
      within collagen, but will almost certainly lead to the development of defined
      reagents that can be used in vitro and ex vivo to explore thrombus formation
      further.

PMID- 16464622
TI  - Cytoskeletal mechanisms for platelet production.
AB  - Platelets release from megakaryocytes living primarily in the bone marrrow space.
      Intermediates in platelet formation are proplatelets, long tube-like processes
      that are extended by microtubule-based forces hundreds of micrometers from the
      megakaryocyte cell body. Granules and organelles enter the proplatelets and
      traffic up and down on their microtubules to be ultimately delivered to the
      platelet buds before they release. How individual platelets form and release from
      proplatelets remains poorly understood.

PMID- 16464623
TI  - The promise of protein C.
AB  - Protein C, a vitamin K-dependent serine protease zymogen that circulates in
      plasma, is converted by limited proteolysis to activated protein C (APC) by the
      thrombin-thrombomodulin complex. APC exerts anticoagulant, antiinflammatory,
      cytoprotective, and antiapoptotic activities. Recombinant APC therapy reduces
      mortality in severe sepsis patients. This review summarizes data from clinical
      observations, from in vitro studies, and from animal models of focal ischemic
      injury that provide a compelling rationale for clinical trials of APC for
      ischemic stroke.

PMID- 16464624
TI  - The Aspergillus nidulans xprG (phoG) gene encodes a putative transcriptional
      activator involved in the response to nutrient limitation.
AB  - The Aspergillus nidulans xprG gene is involved in the regulation of extracellular
      proteases. A plasmid which complemented the xprG2 mutation was shown to carry the
      phoG gene, reported to encode an acid phosphatase. Two phoGDelta mutants were
      constructed and were identical in phenotype to an xprG2 mutant. Null mutants were
      unable to use protein as a carbon or nitrogen source, have lost a repressible
      acid phosphatase and have pale conidial color. XprG shows similarity to the Ndt80
      transcriptional activator, which regulates the expression of genes during meiosis
      in Saccharomyces cerevisiae. The xprG1 gain-of-function mutant contains a
      missense mutation in the region encoding the putative DNA-binding domain. The
      response to carbon, nitrogen, sulfur, and phosphate limitation is altered in
      xprG(-) mutants suggesting that XprG is involved in a general response to
      starvation. Ndt80 may also be involved in sensing nutritional status and control
      of commitment to meiosis in S. cerevisiae.

PMID- 16464626
TI  - Ethnoveterinary medicine in the era of evidence-based medicine: mumbo-jumbo, or a
      valuable resource?

PMID- 16464625
TI  - Functional identification of high-affinity iron permeases from Fusarium
      graminearum.
AB  - The ScFTR1 gene encodes an iron permease in Saccharomyces cerevisiae. Its
      homologues, FgFtr1 and FgFtr2, were identified from filamentous pathogenic plant
      fungus, Fusarium graminearum. Homologies between the deduced amino acid sequences
      of ScFtr1p and FgFtr1 and FgFtr2 were 56 and 54%, respectively, and both had
      REXXE sequences, which form the conserved amino acid sequence of ScFtr1p. FgFtr1
      expression increased under iron depletion, and although FgFtr2 mRNA was not
      detected in the wild-type strain, it was detected in the deltafgftr1 strain in
      the iron-depleted condition. When the FgFtr1 and FgFtr2 were deleted, the amount
      of growth was found not to be different from the wild-type in iron-depleted
      media. However, the mRNA of FgSid, a homologue of the SIDA of Aspergillus
      fumigatus, was dramatically increased in the deltafgftr1/deltafgftr2 strain and
      in an iron-depleted condition. FgFtr1 and FgFtr2 genes act as functional
      complements when they are introduced into the S. cerevisiae deltaScftr1 strain.
      The deltaScftr1 strain, which contains either the FgFtr1 or FgFtr2, grew well in
      iron-depleted media. Moreover, specific alteration of the REXXE consensus
      sequence of FgFtr1 and FgFtr2 did not allow for sustained growth of the
      deltaScftr1 strain on iron-depleted medium. The iron uptake activity was
      recovered when FgFtr1 and FgFtr2 genes were introduced into the deltaScftr1
      strain. Though the Fet3p in S. cerevisiae was found on the intracellular vesicle
      in the deltaScftr1 strain, Fet3p was found on the plasma membrane when FgFtr1 or
      FgFtr2 was introduced into the deltaftr1 strain. An infection test was carried
      out with deletion strains; however, no change in the ability of these strains to
      cause disease was observed. These results suggest that FgFtr1 and FgFtr2 may
      function as iron permeases in the reductive iron uptake pathway and that they do
      not play major roles in the pathogenicity of F. graminearum.

PMID- 16464628
TI  - Tetrahedral versus hexahedral finite elements in numerical modelling of the
      proximal femur.
AB  - The objective of this study was to evaluate and compare tetrahedral and
      hexahedral finite element meshes of simplified and realistic proximal intact
      femur geometries. Theoretical expressions of stresses and strains were derived
      for the simplified model of the femur. For the analysis of the realistic geometry
      of the proximal femur, a CAD model of the third generation composite femur
      (Pacific Research Labs, Vashion Island, WA) was used and simulations were
      performed with Hyperworks (Altair Engineering, Inc., Troy, MI) finite element
      analysis software. Convergence tests with hexahedral (8- and 20-node brick
      elements) and tetrahedral (4- and 10-node tetrahedrons) elements were analysed by
      comparing the periosteal von Mises stresses and principal strains at a selected
      point of the femur. The numerical periosteal strains were also compared with
      experimental ones to determine the accuracy of the finite elements. Overall, we
      concluded, for the simplified femur, that tetrahedral linear element allowed
      results more closely to theoretical ones, but hexahedral quadratic elements seem
      to be more stable and less influenced to the degree of refinement (NDOF) of the
      mesh. It was not possible to correlate these findings with those observed for the
      realistic proximal femur simulations where no significant differences were seen
      using refined meshes, with more than NDOF=20,000 for hexahedral elements.

PMID- 16464627
TI  - SanJ, an ATP-dependent picolinate-CoA ligase, catalyzes the conversion of
      picolinate to picolinate-CoA during nikkomycin biosynthesis in Streptomyces
      ansochromogenes.
AB  - Nikkomycins, a group of peptidyl nucleoside antibiotics, are competitive
      inhibitors of chitin synthase. The nikkomycin biosynthetic gene cluster has been
      cloned previously from Streptomyces ansochromogenes. The cluster contains 25
      complete ORFs including sanJ. The sanJ gene was inactivated by the insertion of a
      kanamycin resistance gene and the resulting disruption mutants failed to produce
      nikkomycins. Moreover, the nikkomycin production was restored by complementation
      with a single copy of sanJ. The deduced product of sanJ bears striking sequence
      similarity with enzymes belonging to the adenylate-forming superfamily. sanJ was
      overexpressed as a His6-tagged fusion protein in Escherichia coli and purified to
      apparent homogeneity by affinity chromatography. The purified SanJ demonstrated
      adenylate ligase activity in the presence of picolinate or its analogs (benzoate,
      nicotinate, 4-methoxybenzoate, 4-hydroxybenzoate), ATP and Mg2+. SanJ was also
      found to catalyze the conversion of picolinate, benzoate, nicotinate to their
      corresponding CoA esters and 4-methoxybenzoate, 4-hydroxybenzoate to their
      respective AMP derivatives in vitro. This was unambiguously shown by using HPLC
      and electrospray ionization mass spectrometry (ESI-MS) or by comparing the
      reaction product with an authentic standard of benzoyl-CoA. These results
      indicated that sanJ encodes an ATP-dependent picolinate-CoA ligase which is
      essential for nikkomycin biosynthesis.

PMID- 16464629
TI  - A retrospective case series of skeletal surveys in children with suspected non
      accidental injury.
AB  - INTRODUCTION: The skeletal survey is widely used as the principal radiological
      investigation in suspected physical abuse of infants and young children. However,
      the evidence on which current guidelines are based is limited, especially for
      siblings of index cases. We conducted a retrospective study to describe the
      characteristics of children who underwent skeletal surveys for suspected non
      accidental injury (NAI) in the Edinburgh area; to evaluate the diagnostic
      efficacy of skeletal surveys; and to identify any predictive factors that might
      guide clinical practice. METHODS: All skeletal surveys performed at the Royal
      Hospital for Sick Children in Edinburgh for suspected non-accidental injury
      between 1/1/99 and 31/12/03 were reviewed. RESULTS: Seventy-seven children
      underwent skeletal surveys for suspected NAI. Data were available for 76 (70
      index cases and 6 siblings). Of the index cases, 17 (24%) skeletal surveys were
      positive, with a mean of 2.5 fractures per child (range 0-9). The age of positive
      cases ranged from 2 weeks to 36 months with the majority (14, 82%) being under 12
      months of age. Nine (53%) were boys. In index children with positive results,
      indications for skeletal survey were head injury (skull fracture in 2, 12%;
      intracranial injury in 4,24%); skeletal fracture (excluding skull fracture) in 6
      (35%) and bruising in 4 (24%). chi(2) analysis revealed no significant
      differences in age, sex or primary reason for skeletal survey between those with
      a negative and positive skeletal survey. Six skeletal surveys were performed on
      siblings of children with known or suspected NAI. The siblings' ages ranged from
      1 to 36 months although 3 (50%) were under 12 months of age. One (17%) of the
      siblings' surveys (a twin) was positive. CONCLUSION: The age of a child (<12
      months) and type of presenting injury (overt fracture or head injury) are factors
      which can help the clinician to decide whether or not to obtain a skeletal
      survey. There remains a lack of evidence for the effectiveness of skeletal survey
      in the siblings of index children. Guidelines for the process of repeating
      uncertain skeletal surveys are needed.

PMID- 16464630
TI  - Point mutations within the LdNT2 nucleoside transporter gene from Leishmania
      donovani confer drug resistance and transport deficiency.
AB  - Leishmania donovani, a protozoan parasite, expresses an unusual inosine/guanosine
      specific transporter, LdNT2, the gene for which was cloned by functional rescue
      of a drug-resistant, LdNT2-deficient (FBD5) strain. In this investigation, we
      have uncovered and characterized the mutations within the LdNT2 open reading
      frame that are the basis for the drug-resistance and transport-incompetent
      phenotype of the FBD5 line. The FBD5 cells were shown to be compound
      heterozygotes in which both mutant ldnt2 alleles harbor discrete point mutations,
      each of which impaired transport function and conferred resistance to formycin B,
      the drug to which the clonal FBD5 line was selected. One of the mutant ldnt2
      alleles encoded an S189L alteration in predicted transmembrane domain 5, while
      the second allele accommodated a null mutation at codon 376, which truncated the
      transporter just prior to transmembrane domain 8. In addition to the null
      transport phenotype, very little S189L ldnt2 mutant transporter targeted to the
      surface of the parasite. The bulk of the truncated ldnt2 appeared to be
      sequestered internally, possibly within the endoplasmic reticulum, but some of
      the truncated transporter seemed to be cell surface exposed. The ability to
      dissect mutations within a viable parasite offers LdNT2 as an attractive model
      for implementing a thorough forward genetic dissection of transporter function in
      a eukaryotic cell.

PMID- 16464631
TI  - Segmentation of volumetric MRA images by using capillary active contour.
AB  - Precise segmentation of three-dimensional (3D) magnetic resonance angiography
      (MRA) images can be a very useful computer aided diagnosis (CAD) tool for
      clinical routines. Level sets based evolution schemes, which have been shown to
      be effective and easy to implement for many segmentation applications, are being
      applied to MRA data sets. In this paper, we present a segmentation scheme for
      accurately extracting vasculature from MRA images. Our proposed algorithm models
      capillary action and derives a capillary active contour for segmentation of thin
      vessels. The algorithm is implemented using the level set method and has been
      applied successfully on real 3D MRA images. Compared with other state-of-the-art
      MRA segmentation algorithms, experiments show that our method facilitates more
      accurate segmentation of thin blood vessels.

PMID- 16464632
TI  - Carcinoma of the buccal mucosa: analysis of clinical presentation, outcome and
      prognostic factors.
AB  - Records of 100 consecutive cases of carcinoma of the buccal mucosa treated in our
      institute between January 2000 and December 2003 were analyzed for clinical
      presentation, patterns of care, disease-free survival (DFS) and prognostic
      factors. There were 75 males and 25 females. The mean age was 50 years. Ninety
      five gave a history of abuse of oral tobacco products. Only 20 patients were in
      Stage I or II. Sixty one patients had Stage IV disease. Sixty six patients were
      treated with radical intent while 34 were suitable only for palliative radiation.
      The 2-year DFS for the entire group was 47.94%. All failures occurred by 12
      months. However, the 2-year DFS in radically treated patients was 76.4%. On
      univariate analysis, late overall stage, T3/T4 disease, node positivity and
      palliative treatment were significant poor prognostic factors. On multivariate
      analysis, T3/T4 disease and palliative treatment were independent poor prognostic
      factors. Early detection can improve outcomes considerably in this disease.

PMID- 16464633
TI  - Cell proliferation and apoptosis culminate in early stages of oral oncogenesis.
AB  - Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were
      studied in an experimental system of induced oral carcinogenesis in Syrian golden
      hamsters. Thirty-seven animals were divided into one control group and three
      experimental groups, which were treated with a carcinogen and sacrificed at 10,
      14 and 19 weeks after treatment. The histological status of the lesions in the
      three experimental groups corresponded well with tumour advancement (from oral
      mucosal dysplasia to moderately differentiated squamous cell carcinoma). Tumour
      sections were studied using monoclonal antibodies against Bax, Bcl-2 and Ki-67
      proteins. Pro-apoptotic Bax expression maintained high levels during all stages
      of oral carcinogenesis. Anti-apoptotic Bcl-2 expression decreased significantly
      in dysplastic and early invasion lesions and consequently increased almost to
      normal tissue level in consequent stages. Finally, Ki-67 expression increased
      sharply in initial stages of oral carcinogenesis, but significantly decreased in
      later stages.

PMID- 16464634
TI  - Assessment of cardiovascular autonomic function.
AB  - Autonomic assessment has played an important role in elucidating the role of the
      autonomic nervous system in diverse clinical and research settings. The
      techniques most widely used in the clinical setting entail the measurement of an
      end-organ response to a physiological provocation. The non-invasive measures of
      cardiovascular parasympathetic function involve the analysis of heart rate
      variability while the measures of cardiovascular sympathetic function assess the
      blood pressure response to physiological stimuli. Prolonged tilt-table testing,
      with or without pharmacological provocation, has become an important tool in the
      investigation of a predisposition to neurally mediated (vasovagal) syncope.
      Frequency domain analyses of heart rate and blood pressure variability,
      microneurography, occlusion plethysmography, laser Doppler imaging and flowmetry,
      and cardiac sympathetic imaging are currently research tools but may find a place
      in the clinical assessment of autonomic function in the future.

PMID- 16464635
TI  - Percutaneous endocardial injection of erythropoietin: assessment of
      cardioprotection by electromechanical mapping.
AB  - BACKGROUND: Apart from its well-known stimulation of erythropoiesis,
      erythropoietin (EPO) exhibits angiogenic and anti-apoptotic effects. These
      cellular protective effects have also been described in experimental acute
      myocardial infarction models. We investigated the effects of EPO in a porcine
      model of chronic progressive myocardial ischaemia. METHODS: At weeks 2 and 6
      after implantation of a circumflex ameroid constrictor, endocardial
      electromechanical NOGA system (Biosense Webster, Inc., California, USA) mapping
      of the left ventricle, coronary and ventricular angiography, as well as
      echocardiography were performed. Two weeks after ameroid placement, 13 pigs were
      randomized with 7 pigs receiving 10.000 U EPO and 6 pigs receiving placebo into
      the ischaemic region using a NOGA guided percutaneous transendocardial injection
      catheter, MYOSTAR. After 6 weeks, histology (Masson's Trichrome) was analyzed.
      RESULTS: Endocardial electromechanical mapping showed an increase of mean
      unipolar voltage (UV) amplitude in the ischaemic myocardial segments in the EPO
      treated animals (8.5 mV pre and 10.6 mV post treatment) and a significantly
      reduced ischaemic surface area compared to the control group (19% vs. 41%)
      suggesting a decline in ischaemic injury. Echocardiography revealed 2,2
      hypokinetic segments of the lateral wall in the EPO group vs. 3,3 in the control
      groups. The mean ejection fraction was 64% in the EPO group and 55% in the
      placebo group. Quantitative histological analysis of the ischaemic regions
      revealed a reduction of myocardial fibrosis (8% vs. 28%) in the EPO group.
      CONCLUSION: Endocardial EPO injection may induce cardioprotective effects in
      hibernating myocardium and may attenuate the progression of ischaemic tissue
      damage.

PMID- 16464636
TI  - Biventricular versus right ventricular pacing decreases immune activation and
      augments nitric oxide production in patients with chronic heart failure.
AB  - INTRODUCTION: Immune system activation and oxidative stress are involved in the
      pathogenesis of heart failure (HF). We aimed to test the hypothesis that
      upgrading from right ventricular pacing (RVp) to biventricular pacing (BiVp) can
      counteract these phenomena. METHODS: 28 HF patients, with BiVp were switched to
      RVp for one week, and then returned to BiVp. Immediately prior to, and 48 h after
      the return to BiVp, left ventricular (LV) systolic function was evaluated by
      echocardiography, and serum N-terminal pro-brain natriuretic peptide (NTproBNP),
      C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interleukin 6
      (IL6), nitric oxide metabolites (NO(x)) and malondialdehyde (MDA) were assayed.
      RESULTS: LV systolic function significantly improved 48 h after switching from
      RVp to BiVp: Ao-VTI (p<0.001), SV (p<0.001) and CO (p<0.001), and mitral
      regurgitation significantly decreased (p=0.003). At the same time, indices of
      peripheral immune activation decreased: TNF-alpha (p=0.02) and IL6 (p<0.001). MDA
      decreased (p<0.001), whereas NO(x) increased (p=0.04). NTproBNP and CRP did not
      change. In addition, in "responders" (i.e. CO increase >10% during BiVp vs. RVp)
      NTproBNP decreased and NO(x) increased. However, during BiVp, the decreases in
      TNF-alpha, IL6, and MDA occurred both in responders and in non-responders and
      were accompanied by a reduction in mitral regurgitation. CONCLUSION: The
      beneficial effect of BiVp compared to RVp extends beyond improving cardiac
      haemodynamics and comprises a decrease in immune activation accompanied by an
      increase in serum NO(x) and decrease in serum MDA.

PMID- 16464638
TI  - Plasma concentrations of the novel peptide apelin are decreased in patients with
      chronic heart failure.
AB  - BACKGROUND: Apelin, the novel endogenous ligand for the G-protein-coupled
      receptor APJ, has shown positive inotropic, vasodilatory and diuretic properties
      in animal studies. Differential expression and synthesis of apelin and APJ
      receptors have been observed in normal and failing human hearts, suggesting a
      possible role in cardiovascular homeostasis. Changes in plasma apelin
      concentrations in relation to heart failure have been described in small studies
      with conflicting results. Our aim was to evaluate plasma apelin concentrations in
      a large cohort of patients with chronic heart failure (CHF) across a broad
      spectrum of disease severity. METHOD AND RESULTS: Plasma apelin concentrations
      were measured in 202 patients with CHF secondary to left ventricular systolic
      dysfunction and 22 age-matched controls. Plasma apelin concentrations were
      significantly lower in patients with CHF, irrespective of NYHA class, ejection
      fraction or aetiology when compared to age-matched controls (0.85 [0.53-2.04]
      versus 3.76 [0.85-5.13] ng/ml, p<0.001). Apelin concentrations were correlated
      with peak VO(2) and right ventricular ejection fraction, but not with age, sex,
      body mass index, renal function or NT-proBNP concentrations. CONCLUSIONS: Plasma
      apelin concentrations are decreased in patients with CHF. The Apelin-APJ
      signaling pathway may be a potentially important mediator in the
      pathophysiological processes of heart failure and may therefore have potential
      therapeutic implications.

PMID- 16464637
TI  - The effect of altering haemodynamics on the plasma concentrations of natriuretic
      peptides in heart failure.
AB  - BACKGROUND: Natriuretic peptide levels reflect haemodynamics in patients with
      heart failure and may serve as biochemical markers of cardiac filling pressures.
      The purpose of this study was to detect differences in the kinetic profile
      between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and
      their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent
      vasodilatation. METHODS: Sixteen men and four women aged 63.0+/-10.4 (mean+/
      S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary
      capillary wedge pressure (PCWP)>18 mm Hg, received a 24-h infusion of
      nitroglycerin (N=8) or nicorandil (N=12). A reduction of PCWP was achieved for
      the duration of the study. Natriuretic peptides were measured by radioimmunoassay
      at baseline, 1, 3, 6, 12 and 24 h. RESULTS: PCWP and right atrial pressure fell
      rapidly and then increased modestly. ANP and N-ANP demonstrated a similar
      pattern. In contrast, BNP and N-BNP levels fell steadily throughout the
      observation period. This was accompanied by a continuous reduction of systemic
      vascular resistance (SVR). PCWP was highly correlated to the levels of all the
      natriuretic peptides. Using a longitudinal regression model evaluating responses
      over time, we found separate, significant relationships between all peptides and
      haemodynamic variables CONCLUSION: The atrial natriuretic peptides reflect rapid
      changes in filling pressures while the B-type peptides respond much slower. B
      type peptides are less sensitive to short-term changes in filling pressures, but
      should reflect changes in SVR better during vasodilator therapy.

PMID- 16464639
TI  - Endovascular clamping of porcelain aorta in aortic valve surgery using Foley
      Catheter.
AB  - Unclampable calcified aorta is an uncommon condition that all cardiac surgeons
      may encounter and performing aortic valve surgery in this condition with a non
      cross-clamping technique of using Foley Catheter has rarely been reported. Aortic
      valve surgery invariably becomes a high-risk, challenging procedure to cardiac
      surgeon or even a contraindication to surgery when the ascending aorta cannot be
      clamped due to extensive calcification precluding safe dissection and clamping.
      We describe and recommend a non cross-clamping technique of using Foley Catheter
      and report it successful use in two patients who underwent aortic valve
      replacement with "porcelain" unclampable aorta.

PMID- 16464640
TI  - Sustained FVIII expression and phenotypic correction of hemophilia A in neonatal
      mice using an endothelial-targeted sleeping beauty transposon.
AB  - Hemophilia A, deficiency of coagulation factor VIII (FVIII), is an attractive
      candidate for gene therapy as expression of modest amounts of FVIII can provide
      therapeutic benefit. Most gene transfer approaches for hemophilia have focused on
      the liver, as this is the major source of endogenous FVIII; however, increasing
      evidence suggests that endothelial cells are capable of synthesis and release of
      FVIII. Here the Sleeping Beauty (SB) transposon is employed to target long-term
      expression of the human B-domain-depleted FVIII gene (approved gene symbol F8)
      within lung endothelia of hemophilic mice. As the formation of inhibitory
      antibodies to FVIII has been a significant impediment toward achieving
      therapeutic plasma levels after gene or protein therapy, we chose to perform gene
      transfer in neonatal mice, which are more likely to be immune tolerant. Using
      this approach, low therapeutic levels of FVIII ( approximately 10%), as well as
      phenotypic correction of the bleeding disorder, were achieved in all animals that
      received the FVIII transposon and functional transposase throughout the duration
      of the study (24 weeks). Rechallenge of these animals with additional gene
      transfer did not result in significant increases in FVIII levels, due mainly to
      increases in inhibitory antibodies. These studies demonstrate the feasibility of
      using endothelial-targeted SB transposons for the treatment of hemophilia A.

PMID- 16464641
TI  - Phosphofructokinase from muscle of the marine giant barnacle Austromegabalanus
      psittacus: kinetic characterization and effect of in vitro phosphorylation.
AB  - The kinetic properties of phosphofructokinase from muscle of the giant cirripede
      Austromegabalanus psittacus were characterized, after partial purification by ion
      exchange chromatography on DEAE-cellulose. This enzyme showed differences
      regarding PFKs from other marine invertebrates: the affinity for fructose 6
      phosphate (Fru 6-P) was very low, with an S(0.5) of 22.6+/-1.4 mM (mean+/-S.D.,
      n=3), and a high cooperativity (n(H) of 2.90+/-0.21; mean+/-S.D., n=3). The
      barnacle PFK showed hyperbolic saturation kinetics for ATP (apparent K(m ATP)=70
      microM, at 5 mM Fru 6-P, in the presence of 2 mM ammonium sulfate). ATP
      concentrations higher than 1 mM inhibited the enzyme. Ammonium sulfate activated
      the PFK several folds, increasing the affinity of the enzyme for Fru 6-P and
      V(max). 5'-AMP (0.2 mM) increased the affinity for Fru 6-P (S(0.5) of 6.2 mM).
      Fructose 2,6-bisphosphate activated the PFK, with a maximal activation at
      concentrations higher than 2 microM. Citrate reverted the activation of PFK
      produced by 0.2 mM 5'-AMP (IC(50 citrate)=2.0 mM), producing a higher inhibition
      than that exerted on other invertebrate PFKs. Barnacle muscular PFK was activated
      in vitro after exposure to exogenous cyclic-AMP (0.1 mM) as well as by
      phosphatidylserine (50 microg/ml), indicating a possible control by protein
      kinase A and a phospholipid dependent protein kinase (PKC). The results suggest a
      highly regulated enzyme in vivo, by allosteric mechanisms and also by protein
      phosphorylation.

PMID- 16464642
TI  - Validation by simulation of a clinical trial model using the standardized mean
      and variance criteria.
AB  - OBJECTIVE: To develop and validate a model of a clinical trial that evaluates the
      changes in cholesterol level as a surrogate marker for lipodystrophy in HIV
      subjects under alternative antiretroviral regimes, i.e., treatment with Protease
      Inhibitors vs. a combination of nevirapine and other antiretroviral drugs.
      METHODS: Five simulation models were developed based on different assumptions, on
      treatment variability and pattern of cholesterol reduction over time. The last
      recorded cholesterol level, the difference from the baseline, the average
      difference from the baseline and level evolution, are the considered endpoints.
      Specific validation criteria based on a 10% minus or plus standardized distance
      in means and variances were used to compare the real and the simulated data.
      RESULTS: The validity criterion was met by all models for considered endpoints.
      However, only two models met the validity criterion when all endpoints were
      considered. The model based on the assumption that within-subjects variability of
      cholesterol levels changes over time is the one that minimizes the validity
      criterion, standardized distance equal to or less than 1% minus or plus.
      CONCLUSION: Simulation is a useful technique for calibration, estimation, and
      evaluation of models, which allows us to relax the often overly restrictive
      assumptions regarding parameters required by analytical approaches. The validity
      criterion can also be used to select the preferred model for design optimization,
      until additional data are obtained allowing an external validation of the model.

PMID- 16464643
TI  - Health dialog systems for patients and consumers.
AB  - There is a growing need for automated systems that can interview patients and
      consumers about their health and provide health education and behavior change
      interventions using natural language dialog. A number of these health dialog
      systems have been developed over the last two decades, many of which have been
      formally evaluated in clinical trials and shown to be effective. This article
      provides an overview of the theories, technologies and methodologies that are
      used in the construction and evaluation of these systems, along with a
      description of many of the systems developed and tested to date. The strengths
      and weaknesses of these approaches are also discussed, and the needs for future
      work in the field are delineated.

PMID- 16464644
TI  - Informed consent procedures: an experimental test using a virtual character in a
      dialog systems training application.
AB  - Researchers are generally trained to administer informed consent by studying
      approved guidelines, but still can fail to satisfactorily answer questions from
      potential participants. An application using a virtual character allowed novice
      participants to practice administering informed consent. This character was
      designed to behave as a potential participant for a study and asked many of the
      questions research participants typically ask, such as queries about the study
      itself, the sponsor, timing, selection procedures, confidentiality,
      voluntariness, benefits and risks, and contact information. The user responded to
      the character's queries as if speaking with a true potential research
      participant. The application was effective even after only brief usage. In a
      laboratory experiment, novice participants who practiced with the virtual
      character were later more effective in conducting informed consent interviews
      with a human interviewee than those who were trained only with written materials.
      Thus, simulated learning-by-doing improved informed consent skills. Implications
      for related health dialog applications are discussed.

PMID- 16464645
TI  - Noradrenergic and cholinergic neural pathways mediate stress-induced reactivation
      of colitis in the rat.
AB  - Evidence to date suggests that stress-induced exacerbation or relapse of
      intestinal inflammation in inflammatory bowel disease requires both activation of
      the autonomic nervous system and the activation of the immune system by the
      presence of previously encountered luminal antigens. The aim of the present study
      was to further explore these associations and to determine the role of the
      autonomic nervous in modulating the intestinal inflammatory response to stress.
      Rats healed from an initial dinitrobenzene sulfonic acid-induced colitis were
      given a non-colitic dose of dinitrobenzene sulfonic acid (dissolved in saline) or
      0.9% saline intra-rectally and then subjected to restraint stress. Cardiac
      sympathovagal balance was assessed by power spectral analysis of heart rate
      variability data collected from telemetric electrocardiogram recordings before,
      during and post stress. Only rats that were stressed and received dinitrobenzene
      sulfonic acid showed an inflammatory relapse characterized by significant
      macroscopic damage and elevated myeloperoxidase activity associated with a
      significant infiltration of mucosal and submucosal T lymphocytes. No difference
      in inflammatory markers was observed in animals that received intra-rectal saline
      and restraint stress. Rats subjected to stress and intra-rectal dinitrobenzene
      sulfonic acid demonstrated an increase in sympathetic activity with a nearly four
      fold increase in LF:HF ratio during stress and a significant increase in heart
      rate. Shortly after cessation of stress, the LF:HF ratio decreased significantly,
      returning to baseline levels, however the heart rate remained significantly
      elevated over baseline levels following stress, but decreased to a level that was
      significantly lower than during stress. The stress/dinitrobenzene sulfonic acid
      induced relapses were preventable by pre-treating rats with hexamethonium (a
      nicotinic cholinergic ganglion blocking agent) or the co-administration of
      atropine (a muscarinic cholinoceptor antagonist) and bretylium (a noradrenergic
      ganglion blocking agent), but was not prevented when either atropine or bretylium
      were administered alone. This study utilizes an established model of chemically
      induced colitis that when integrated with stress results in relapsing
      inflammatory bowel disease. Moreover, this study demonstrates that noradrenergic
      and cholinergic neural pathways mediate the stress response critical for the
      relapse of colitis.

PMID- 16464647
TI  - Effect of jejunal nutrition on pancreatic exocrine secretion in pancreatitis rats
      and the involvement of the nucleus tractus solitarius.
AB  - Jejunal nutrition is currently used as a fundamental therapeutic measure for
      acute pancreatitis. Its impact on pancreatic exocrine secretion (PES) is still on
      dispute. The aim of this study was to determine the effect of jejunal nutrition
      on PES and illuminate whether NTS is involved in the regulation of PES. Firstly,
      we established experimental acute cutaneous pancreatitis (ACP) and acute necrotic
      pancreatitis (ANP) rat models, and measured the volume and protein levels of
      pancreatic fluid in normal and pancreatitis rats, and found that pancreatitis
      rats had a significantly lower pancreatic fluid volume and protein level than the
      normal rats. Then, we gave 0.3 mol/l maltose and 3% saline as jejunal nutrition
      were given to the two groups, respectively, and found that the jejunal nutrition
      did not increase the PES levels in both groups. In addition, we analyzed c-Fos
      expression in the nucleus tractus solitarius (NTS), and found c-Fos expression in
      NTS was stronger in rats who were given the jejunal nutrition than in those who
      were not. These findings suggest that jejunal nutrition excites vagal afferent
      nerve fibers at pancreatitis rats, and the excitation can be transmitted to
      medulla oblongata, but do not induce changes in PES. It is likely that the
      central integration mechanism, pathway of vagal efferent nerve or status of
      effector in acute pancreatitis may be different from normal physiological
      conditions.

PMID- 16464646
TI  - Opposite to alpha2-adrenergic agonists, an imidazoline I1 selective compound does
      not influence reflex bradycardia in rabbits.
AB  - This work aimed to study the respective effects of central alpha2-adrenergic
      receptors (alpha2-ARS) and I1 imidazoline receptors (I1Rs) in the facilitatory
      effects of imidazoline-like drugs on the reflex bradycardia (RB). Experiments
      were performed in anaesthetized rabbits. The reflex bradycardic response was
      induced by phenylephrine injected i.v. LNP 509, rilmenidine and dexmedetomidine
      were administered intracisternally (i.c.). LNP509 (1 mg/kg, i.c.), a ligand
      highly selective for I1Rs, induced hypotension (54+/-3 vs. 93+/-2 mm Hg) and
      bradycardia (260+/-13 vs. 322+/-13 beats/min) (p<0.05, n=5) but did not affect
      RB. Rilmenidine (1 microg/kg, i.c.), a hybrid ligand which binds to both I1 and
      alpha2-ARS, also decreased arterial pressure (61+/-2 vs. 101+/-2 mm Hg) and heart
      rate (260+/-4 vs. 308+/-8) (p<0.01, n=5); it potentiated the RB (maximum R-R
      interval: 284+/-17 vs. 196+/-6 ms) (p<0.05, n=5). Dexmedetomidine (1 microg/kg,
      i.c.), a ligand selective for alpha2-ARs, reduced blood pressure (53+/-3 vs.
      104+/-2 mm Hg) and heart rate (246+/-4 vs. 312+/-8 beats/min) (p<0.05, n=5) and
      potentiated the RB (maximum R-R interval: 518+/-38 vs. 194+/-4 ms) (p<0.05, n=5).
      The potentiation of RB was much greater than that observed with rilmenidine and
      was significantly prevented by L-NNA injected centrally. This study shows that:
      (i) an exclusive action on I1Rs which decreases arterial pressure, does not
      potentiate the RB ii) activation of alpha2-ARs potentiates the RB (iii) the R-R
      prolongation caused by alpha2-ARs stimulation is prevented by central NOS
      inhibition.

PMID- 16464648
TI  - Synthesis of DnaK and GroEL in Escherichia coli cells exposed to different
      magnetic field signals.
AB  - The effects of extremely low frequency magnetic field (ELF-MF)(1 mT, 50 Hz) on
      the heat shock protein (HSP) synthesis in Escherichia coli were investigated. Two
      magnetic field signals were studied: sinusoidal (SMF) and pulsed square wave
      (PMF). It was found that bacteria exposed to SMF showed a significantly higher
      level of DnaK and GroEL proteins as compared to sham-exposed bacteria as revealed
      by Western blot, whereas a lower level was observed after PMF exposure. Similar
      results were obtained when bacterial cells were exposed to heat shock (HS) after
      ELF-MF exposure: again SMF and PMF resulted in an increase and in a reduction of
      HSP amount in comparison with sham control, respectively. In conclusion, the MF
      influences the synthesis of HSPs in E. coli in a way that critically depends on
      the signal characteristics.

PMID- 16464649
TI  - Efficient removal of albumin from human serum by monosize dye-affinity beads.
AB  - Cibacron Blue F3GA was covalently attached onto monosize poly(glycidyl
      methacrylate) [poly(GMA)] beads for removal of human serum albumin (HSA) from
      human serum. Monosize poly(GMA) beads, 1.6 microm in diameter, were produced by
      dispersion polymerization. Cibacron Blue F3GA loading was 1.73 mol/g. HSA
      adsorption experiments were performed by stirred-batch adsorption. The non
      specific adsorption of HSA was low (0.8 mg/g polymer). Dye attachment onto the
      monosize beads significantly increased the HSA adsorption (189.8 mg/g). The
      maximum HSA adsorption was observed at pH 5.0. With an increase of the aqueous
      phase concentration of sodium chloride, the adsorption capacity decreased
      drastically. The equilibrium adsorption of HSA significantly decreased with
      increasing temperature. The elution studies were performed by adding 0.1 M
      Tris/HCl buffer containing 0.5 M NaSCN to the HSA solutions in which adsorption
      equilibria had been reached. The elution results demonstrated that the adsorption
      of HSA to the adsorbent was reversible. The depletion efficiencies for HSA were
      above 87% for all studied concentrations. To test the efficiency of HSA removal
      from human serum, proteins in the serum and eluted portion were analyzed by two
      dimensional gel electrophoresis. Eluted proteins include mainly albumin, and a
      small number of nonalbumin proteins such as apo-lipoprotein A1, sero-transferrin,
      haptoglobulin and alpha1-antitrypsin were bound by the dye-affinity beads. IgA
      was not identified in eluted fraction.

PMID- 16464650
TI  - Quantification of isosorbide 5-mononitrate in human plasma by liquid
      chromatography-tandem mass spectrometry using atmospheric pressure
      photoionization.
AB  - Isosorbide 5-mononitrate (5-ISMN) is an organic nitrate widely used for its
      vasodilating properties in the treatment of angina pectoris. In the present
      study, an efficient, sensitive, robust method was developed for the determination
      and quantification of isosorbide 5-mononitrate, in human plasma, by liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS), using photospray
      ionization. Isosorbide 5-mononitrate was extracted from 0.5 mL human plasma by
      liquid-liquid extraction (LLE). The method had a chromatographic run of 2.0 min
      using a C(8) analytical column (100 mm x 2.1 mm i.d.) and the linear calibration
      curve over the range was linear from 20 to 2000 ng mL(-1) (r(2)>0.995). The
      between-run precision, based on the relative standard deviation replicate quality
      controls, was 7.9% (60 ng mL(-1)), 5.2% (300 ng mL(-1)) and 7.0% (1800 ng mL(
      1)). The between-run accuracy was 94.9%, 94.1% and 88.8% for the above-mentioned
      concentrations, respectively. The method herein described was employed in a
      bioequivalence study of two tablet formulations of isosorbide 5-mononitrate 40
      mg.

PMID- 16464651
TI  - Adefovir dipivoxil-associated thrombocytopenia in a patient with chronic
      hepatitis B.
AB  - A 56-year-old male patient received adefovir dipivoxil (10 mg/day) for chronic
      hepatitis B resistant to lamivudine. On the fifth week of treatment, the platelet
      count dropped to 26 x 10(3) mm(-3); anti-platelet antibodies were detectable in
      serum. The drug was discontinued and the platelet count improved spontaneously. A
      re-challenge with adefovir caused a new episode of thrombocytopenia, again after
      a five-week treatment period. To date, thrombocytopenia has not been described
      after adefovir therapy for chronic hepatitis B and seems to be a rare event.

PMID- 16464652
TI  - Serum antibodies to enterohepatic Helicobacter spp. in patients with chronic
      liver diseases and in a population with high prevalence of H. pylori infection.
AB  - BACKGROUND: Enteric Helicobacter species might be a risk factor for chronic liver
      and biliary tract diseases. AIMS: To analyse serum antibody levels to three
      enteric Helicobacter species in patients with various biliary tract and chronic
      liver diseases and compare results with corresponding parameters for an adult
      population group, known to have a high prevalence of Helicobacter pylori
      infection, and with healthy blood donors, to explore a possible association of
      enteric Helicobacter with chronic liver diseases. SUBJECTS: Sera of 90 patients
      with various chronic liver diseases, 121 Estonian adult persons and 68 blood
      donors were analysed. METHODS: Sera, previously tested for H. pylori were
      analysed for IgG to Helicobacter hepaticus, Helicobacter bilis and Helicobacter
      pullorum. ELISA was initially used for screening and exclusion of negative cases.
      Sera with positive ELISA results were further analysed by immunoblot. To remove
      cross-reactive antibodies between H. pylori and the enteric species, sera were
      pre-absorbed with lysed H. pylori cells. RESULTS: Liver patients showed a
      significantly higher seroprevalence to H. hepaticus and H. bilis, compared with
      the adult population group (p=0.0001 and 0.04, respectively), and to H.
      hepaticus, compared with blood donors (p=0.01). Patients with autoimmune
      hepatitis showed no significant antibody reactivity to the enteric Helicobacter
      spp. in contrast to patients with other chronic liver diseases. CONCLUSION:
      Patients with chronic liver diseases, except autoimmune hepatitis patients,
      showed increased antibody levels to H. bilis/H. hepaticus compared with the
      population and blood donors indicating a possible role of enteric Helicobacter in
      the natural course of chronic liver diseases. Immunoblot seems to be a promising
      method for serodiagnosis of infections with these fastidious pathogens.

PMID- 16464653
TI  - Low serum levels of 25-hydroxy vitamin D in adults affected by thalassemia major
      or intermedia.
AB  - Adult thalassemic patients have reduced bone mass due to disturbances in several
      different mechanisms affecting bone turnover. To determine if vitamin D
      deficiency contributes to the low bone mass of adult thalassemic subjects, we
      studied serum 25-OH-vitamin D levels in 90 patients (age ranging between 21 and
      48 years) affected with thalassemia major (TM) and 35 (age 21-56 years) with
      thalassemia intermedia (TI). TM patients had been receiving regular transfusions
      from the age of 2 years and had increased serum ferritin, glutamic oxalacetic
      transaminase, glutamic piruvic transaminase as well as low bone density (L1-L4 Z
      score -2.07 +/- 0.2). TI patients did not receive transfusions, but their
      ferritin levels were increased as well (520.3 +/- 138,1). 8 TM patients (10.1%)
      and 4 TI (11.4%) had serum 25-OH-vitamin D less than 10.4 ng/ml and were
      considered presenting an absolute deficiency of vitamin D. Mean 25-OH-vitamin D
      was significantly (P < 0.01) lower in both TM and TI patients (20.3 +/- 0.7 ng/ml
      and 20.9 +/- 2.3 ng/ml, respectively) than in 100 healthy control subjects of
      similar age (25.2 +/- 1 ng/ml). 1,25-OH-vitamin D levels were in the normal-lower
      levels (45.15 +/- 1.5 mg/dl), while 24 H urinary calcium was below the normal
      range (15.75 mg/dl). In TM patients, the 25-OH-vitamin D levels correlated
      negatively with age (P < 0.05) and with serum ferritin (P < 0.05). TM and TI
      patients with low 25-OH-vitamin D levels (<17.8 ng/ml) presented higher serum
      ferritin levels (P < 0.01) and higher PTH (P < 0.05) compared to those with
      normal vitamin D. Moreover, TM patients with low 25-OH-vitamin D levels were
      significantly older (P < 0.05) and had higher GPT (P < 0.05) than patients with
      normal vitamin D. In conclusion, calcium metabolism is frequently impaired in
      adult thalassemic patients. An early and effective medical treatment should be
      taken in consideration by the clinician in order to improve the bone health in
      these patients.

PMID- 16464654
TI  - Analysis of a polymorphism in the DGAT1 gene in 14 cattle breeds through PCR-SSCP
      methods.
AB  - The diacylglycerol O-acyltransferase (DGAT1) is a microsomal enzyme that
      catalyzes the final step of triglyceride synthesis. Recent work have evidenced a
      significant association between lysine at amino acid position 232 with elevated
      milk fat content, while an alanine at this position is associated with lowered
      milk fat content. The aim of the present work was to develop a simple and
      inexpensive PCR-SSCP assay in order to discriminate the CG/AA alleles in exon 8
      of the DGAT1 gene. In addition, this method was used to analyze the polymorphism
      of the DGAT1 through PCR-SSCP methods in 14 populations of cattle from Argentine,
      Bolivia and Uruguay. The PCR primers were designed from GenBank reported
      sequences. In this study, we found three PCR-SSCP variants, which were
      denominated from "A" to "C". However, DNA sequencing analysis showed that "A"
      variant corresponded with the A allele, while both "B" and "C" observed pattern
      have the motif AA at positions 10,433-10,434 (K allele), being two alternative
      conformations of the same DNA sequence. Both variants were detected within each
      breed with the exception of Hereford, and the heterozygosity varied between 0.000
      and 0.524. The gene frequency analysis evidenced significant differences among
      the studied breeds (F(ST) = 0.325, p = 0.000). European Bos taurus breeds, with
      the exception of Jersey breed, showed the lowest frequency of the K allele, while
      highest K allele frequencies were harboured by Bos indicus type cattle. In
      addition, unselected South American Creole cattle breeds and the synthetic
      Brangus breed had intermediate allele frequencies.

PMID- 16464656
TI  - Amyloid peptides mediate hypoxic increase of L-type Ca2+ channels in central
      neurones.
AB  - Prolonged hypoxia, encountered in individuals suffering from various
      cardiorespiratory diseases, enhances the likelihood of subsequently developing
      Alzheimer's disease (AD). However, the underlying mechanisms are unknown, as are
      the mechanisms of neurodegeneration of amyloid beta peptides (AbetaPs), although
      the latter involves disruption of Ca2+ homeostasis. Here, immunohistochemistry
      demonstrated that hypoxia increased production of AbetaPs, an effect which was
      prevented by inhibition of either beta or gamma secretase, the enzymes required
      for liberation of AbetaP from its precursor protein. Whole-cell patch clamp
      recordings showed that hypoxia selectively increased functional expression of L
      type Ca2+ channels. This was prevented by inhibition of either beta or gamma
      secretase, indicating that hypoxic channel up-regulation is dependent upon AbetaP
      formation. Our results indicate for the first time that hypoxia promotes AbetaP
      formation in central neurons, and show that this leads to abnormally high
      selective expression of L-type Ca2+ channels whose blockade has previously been
      shown to be neuroprotective in AD models. These findings provide a cellular basis
      for understanding the increased incidence of AD following prolonged hypoxia.

PMID- 16464655
TI  - In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors.
AB  - Glycogen synthase kinase-3 (GSK3), which is inhibited by serine-phosphorylation,
      is involved in the neuropathology of Alzheimer's disease (AD). We tested if the
      two therapeutic strategies used for AD, inhibition of acetylcholinesterase and of
      N-methyl-D-aspartate (NMDA) receptors, modulate the phosphorylation state of the
      two isoforms of GSK3 in mouse brain. Large, rapid increases in the levels of
      phospho-Ser21-GSK3alpha and phospho-Ser9-GSK3beta occurred in mouse hippocampus,
      cerebral cortex, and striatum after treatment of mice with the muscarinic agonist
      pilocarpine or the acetylcholinesterase inhibitor physostigmine. Treatment with
      memantine, an NMDA receptor antagonist, also increased the serine-phosphorylation
      of both GSK3 isoforms in mouse brain. Co-administration of physostigmine and
      memantine increased serine-phosphorylated GSK3 levels equally to that achieved by
      either agent alone, indicating that the actions of these two drugs converge on
      overlapping pools of GSK3. Thus, drugs in each class of therapeutic agents used
      for AD have the common property of increasing the regulatory serine
      phosphorylation of GSK3 within common pools of the enzyme.

PMID- 16464657
TI  - Association of folate with hearing is dependent on the 5,10
      methylenetetrahdyrofolate reductase 677C-->T mutation.
AB  - Vascular disease and its risk factors have been associated with the age-related
      hearing loss. We examined the association of elevated plasma homocysteine and its
      determinants with hearing levels. Pure-tone air conduction thresholds in 728
      individuals with sensorineural hearing loss were not associated with
      homocysteine, erythrocyte folate and Vitamin B6. Low concentrations of serum
      folate and Vitamin B12 were associated with better hearing. When folate status
      was below the median, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677TT
      homozygotes had similar hearing levels to subjects with a C allele. However, when
      folate status was above the median, MTHFR 677TT homozygotes had on an average 5
      dB (p = 0.037) and 2.6 dB (p = 0.021) lower PTA-high and PTA-low hearing
      thresholds, respectively, than the subjects with a 677C allele. The relationship
      between serum folate and hearing thresholds appeared to be dependent on MTHFR 677
      genotype (CC, r = 0.13, p = 0.034; TT, r = -0.10, p = 0.291). This supports the
      hypothesis that a greater one-carbon moiety commitment to de novo synthesis of
      nucleotides and an increase in formyl-folate derivatives relative to methyl
      folate derivatives is protective for hearing.

PMID- 16464658
TI  - Age-related changes in cochlear and brainstem auditory functions in Fischer 344
      rats.
AB  - Auditory function in Fischer 344 (F344) and Long Evans (LE) rats was monitored
      during their lifespan by evaluating hair cell loss, middle-ear compliance and the
      recording of otoacoustic emissions and auditory brainstem responses. The results
      revealed a faster deterioration of hearing function in F344 rats compared with LE
      rats, resulting in larger hearing threshold shifts, a decrease in the latency and
      amplitude of click-evoked auditory brainstem responses, diminution of the
      distortion product otoacoustic emissions and a decrease in middle-ear compliance.
      However, hair cell loss, observed only at the most basal and apical parts of the
      organ of Corti, was comparable in older individuals of both rat strains. The
      results suggest involvement of cochlear (stria vascularis) and extracochlear
      (middle-ear) pathological changes during ageing. Thus, F344 rats represent a
      complex mix of conductive hearing loss (with low-frequency threshold shift,
      declining parameters of the middle-ear admittance and asymmetric otoacoustic
      emissions) and sensorineural hearing loss (with a decrease in the amplitudes of
      auditory brainstem response and a high-frequency threshold shift).

PMID- 16464659
TI  - SIRT1, neuronal cell survival and the insulin/IGF-1 aging paradox.
AB  - Signaling through the insulin/IGF-1 pro-survival pathway is widely recognized to
      be neuroprotective as well as important for neuronal growth and physiology. In
      mammals, age-associated decline in circulating IGF-1 levels has been associated
      with neuronal aging and symptoms of neurodegeneration. Defects in IGF-1 receptor
      associated signaling has, however, been shown to significantly extend lifespan in
      models ranging from invertebrates to mouse. At least in C. elegans, restoring
      such defects in neurons alone reduces lifespan to wild-type levels. As we seek to
      delay brain aging and age-associated neuronal degeneration via nutritional and
      endocrinal supplements, an understanding of the mechanistic basis of this
      apparent paradox is important. Recent elucidation of the role of the protein
      deacetylase SIRT1 in cell survival and data associating IGF-1 with the regulation
      of SIRT1 expression may provide a direction towards resolving this issue.

PMID- 16464660
TI  - Subendometrial arterial spectral doppler assessment during IVF cycles and its
      correlation with treatment outcome.
AB  - The influence of blood flow impedance in subendometrial arteries on embryo
      implantation rate was investigated by transvaginal sonographic examination in in
      vitro fertilization (IVF) cycles. A total of 39 women undergoing IVF treatment
      were evaluated along the treatment cycle. Power and spectral Doppler studies of
      subendometrial arteries were performed to calculate the pulsatility index (PI),
      resistance index (RI) and systolic:diastolic ratio (S:D). The correlation between
      these parameters and pregnancy achievement was analyzed. Patients were grouped
      according to whether pregnancy was achieved or not. RI and S:D did not differ
      between the groups along the course of treatment. In pregnant patients, the PI
      was significantly lower in the beginning of the cycle than on the preovulation
      day and ovum pickup day. PI in the beginning of the treatment was significantly
      lower in pregnancy cycles than in nonpregnancy ones. A lower PI on day 1 was
      correlated with a better chance for pregnancy.

PMID- 16464661
TI  - Assessment of cyclic changes of microvessels in ovine ovaries using Sonovue
      contrast-enhanced ultrasound.
AB  - Our objective was to detect variations of ovarian vascularization that occur in
      the estrus cycle of the ewe using an IV contrast agent. Five ewes were
      investigated using contrast-enhanced power Doppler after Sonovue injection at day
      0, 3, 5, 10 and 13 of the cycle in two successive estrus cycles. Transvaginal
      ultrasound monitoring of each ewe was performed after a dose of Sonovue.
      Parameters derived from the time-intensity curves were compared. Quantification
      of the enhancement and wash-in period parameters changed significantly between
      ovaries and between the follicular and luteal periods of the cycle. Uptake time,
      wash-out time, total time of enhancement and area under the curve were the
      parameters with the smallest variation between ovaries. Wash-out time and area
      under the curve are two contrast parameters that did not change with cyclic
      changes. Thus, using these parameters in premenopausal women will allow more
      accurate detection of vascular modifications that may be associated with ovarian
      cancer.

PMID- 16464662
TI  - Colour doppler ultrasound of the lumbar arteries: a novel application and
      reproducibility study in healthy subjects.
AB  - Lumbar arteries are important because they are the main source of blood supply to
      the lumbar spine structures. However, these vessels and their flow
      characteristics have received little attention and their role in conditions such
      as low back pain remains unclear. The present study 1. describes the application
      of duplex ultrasonography in the assessment of lumbar artery blood flow and 2.
      evaluates the interobserver and intraobserver reproducibility of lumbar artery
      Doppler velocimetry. A total of 13 healthy volunteers were evaluated by two
      different examiners successively on the same day and measurements repeated by the
      same examiners 1 week later. Peak systolic velocities of lumbar arteries were
      recorded at an optimal angle below 60 degrees . Overall mean peak systolic
      velocity (+/-SD) for lumbar arteries was 0.158 +/- 0.051 m/s, and mean Doppler
      angle (+/-SD) was 24.6 +/- 14.5 degrees . For interobserver variability, the
      coefficient of variation was 23.4% and SD of differences 0.037 m/s. Reliable
      results of lumbar artery Doppler velocimetry demonstrate its applicability in
      future clinical investigations in patients with low back disorders. (E-mail: ).

PMID- 16464663
TI  - High-frequency ultrasound detection and follow-up of Wilms' tumor in the mouse.
AB  - The goal of this study was to validate high-frequency (24 MHz) ultrasound imaging
      techniques for early detection and follow-up of renal tumors in a murine Wilms'
      tumor model (n = 26). For 11 mice, maximum tumor dimensions were estimated from
      images along three orthogonal axes for comparison with posteuthanasia caliper and
      histologic measurements. Tumor size in the 15 remaining mice was checked
      biweekly. The mice were then euthanized and histologic study assessed tumor
      position and nature. Tumors were detected in vivo between 7 to 14 days after
      injection of tumor-inducing cells. Tumor maximum cross-sectional area varied from
      0.07 mm2 to 5.7 mm2 at the time of initial detection. The relative r.m.s. error
      between ultrasonic and histologic estimations of maximum cross-sectional area was
      estimated to be 19%. Results demonstrate feasibility of noninvasive ultrasound
      biomicroscopy early detection and characterization of renal tumor development for
      longitudinal monitoring of the same animal.

PMID- 16464664
TI  - Quantitative ultrasound at the hand phalanges in patients with acromegaly.
AB  - The aim of this study was assessment of skeletal status using quantitative
      ultrasound (QUS) at hand phalanges in patients with acromegaly. A group of 38
      patients with acromegaly (27 women and 11 men) with a mean age of 57.21 +/- 9.85
      years was compared with a control group of 44 men and 108 women matched for
      gender, age and body size. Amplitude-dependent speed of sound (Ad-SoS) at hand
      phalanges had lower values in patients with acromegaly than in controls, both in
      the entire group and in men and women, respectively. The positive correlation
      between Ad-SoS and height and the negative one between Ad-SoS and age was found
      in the entire group of patients with acromegaly. No correlations between Ad-SoS
      and time from diagnosis or duration of the symptoms were found. Age affected Ad
      SoS significantly less in the entire patient group than in controls. Similarly,
      in women, age and body mass affected Ad-SoS less than in controls. A stepwise
      multiple regression analysis carried out in the patient group identified age as
      the only factor significantly influencing negatively the Ad-SoS value (regression
      equation: Ad-SoS (m/s) = 2124 m/s - 3.26 x age (years) [r2= 0.26, standard error
      of estimate = 55.1, p < 0.01]). In conclusion, our data demonstrate that, in
      patients with acromegaly, skeletal status assessed by QUS was affected. This
      could reflect the worsening of the mechanical properties of bones studied and the
      increased risk of fractures in other sites of the skeleton. The changes observed
      were not related to acromegaly-associated hypogonadism. Further studies to assess
      the role of QUS in acromegaly are necessary and fracture prevalence and risk
      ought to be established.

PMID- 16464666
TI  - Young's modulus reconstruction of vulnerable atherosclerotic plaque components
      using deformable curves.
AB  - Rupture, with subsequent thrombosis, of thin-cap fibroatheromas (TCFAs) is a
      major cause of myocardial infarction. A TCFA has two main components: these are a
      large, soft lipid pool and a thin, stiff fibrous cap covering it. Quantification
      of their morphology and stiffness is essential for monitoring atherosclerosis and
      quantifying the effect of plaque-stabilizing pharmaceutical treatment. To
      accomplish this, we have developed a model-based Young's modulus reconstruction
      method. From a plaque strain elastogram, measured with an intravascular
      ultrasound catheter, it reconstructs a Young's modulus image of the plaque. To
      this end, a minimization algorithm automatically varies the morphology and
      stiffness parameters of a TCFA computer model, until the corresponding computer
      simulated strain elastogram resembles the measured strain elastogram. The
      morphology parameters of the model are the control-points of two deformable
      Bezier curves; one curve delineates the distal border of the lipid pool region,
      the other the distal border of the cap region. These component regions are
      assumed to be homogeneous and their stiffness is characterized by a Young's
      modulus. Reconstructions from strain elastograms that were 1. simulated using a
      histology-derived computer TCFA, 2. measured from a physical phantom with a soft
      lipid pool, and 3. simulated with a computer TCFA, where the complexity of its
      plaque component borders was increased, demonstrated the superior
      reconstruction/delineation behavior of this method, compared with a previously
      developed circular reconstruction method that used only circles for border
      delineation. Consequently, this method may become a valuable tool for the
      quantification of both the morphology and stiffness of vulnerable atherosclerotic
      plaque components.

PMID- 16464665
TI  - Use of ultrasound for diagnosis of interposition of soft tissue in bone fracture
      line.
AB  - Ultrasound (US) has recently become a favorable diagnostic technique in
      orthopedics and traumatology, as well as in other medical sciences. We aimed to
      determine effectiveness of US in diagnosis of soft tissue interposition that
      impedes or delays the union of fracture. The present study included 55 acute
      fractures in 39 patients, in whom operation (open reduction and internal
      fixation) was scheduled because no closed reduction was achieved, in our
      department between January 1999 and December 2003. Before the operation, the
      fracture line in all patients was scanned by a 5- to 7-MHz linear probe of the US
      device. The data obtained by US examination were compared to findings obtained by
      surgical intervention with the McNemar test. These were calculated as positive
      predictive value and negative predictive value, with specificity and sensitivity.
      The difference between the study and control groups was not statistically
      significant (p = 0.625). These findings demonstrated that sensitivity value,
      specificity value, positive and negative predictive values were 96.9%, 86.3%,
      91.4% and 95%, respectively. US is an efficient, safe and reliable diagnostic
      technique for detection of interposition of soft tissue in bone fracture line.

PMID- 16464667
TI  - The estimation of elasticity and viscosity of soft tissues in vitro using the
      data of remote acoustic palpation.
AB  - The presented study revealed the significant dependence of displacement magnitude
      and strain relaxation on phantom elasticity and viscosity. It has been shown that
      simultaneous analysis of temporal behavior and magnitude of shear strain induced
      by the radiation force of focused ultrasonic beam gives the necessary data for
      quantitative estimation of tissue shear modulus because of the known functional
      dependencies of displacement on local viscosity and elasticity. As a result, the
      simplest calibration procedure of acoustic radiation force-based methods is
      performed and algorithm for separate reconstruction of tissue elasticity and
      viscosity is proposed. These findings were tested, in particular, using the data
      obtained for specially prepared phantoms containing calf liver and muscle tissue
      in vitro. The observed complex character of shear strain relaxation and noise in
      some tissue phantoms and tissues in vitro reduces the preciseness of viscoelastic
      properties estimation.

PMID- 16464668
TI  - Identifying the mechanical properties of tissue by ultrasound strain imaging.
AB  - A new elastography method is presented that images the mechanical properties of
      soft tissue. The tissue is externally vibrated over a range of frequencies
      simultaneously and the resulting displacement is recorded at multiple locations
      and time instants with a sequence of ultrasound images. Two methods are proposed
      for estimating the mechanical properties from the recorded data. In the first
      method, equations of motion are written for a tissue model of masses, springs and
      dampers. The equations are solved to identify the model parameters and construct
      an image. The second method performs a transfer function analysis of the tissue
      motion. The tissue properties are identified from the shape the of transfer
      function. Simulations show good performance of the new method compared with
      static elastography. Initial experimental results from homogeneous and layered
      tissue phantoms also demonstrate the ability quantitatively to image tissue
      stiffness. Preliminary results are obtained for viscosity and density estimation.
      Further work is needed to extend the formulation to 3-D and improve robustness of
      the viscosity and density estimates.

PMID- 16464669
TI  - Breast ultrasound image enhancement using fuzzy logic.
AB  - Breast cancer is still a serious disease in the world. Early detection is very
      essential for breast cancer prevention and diagnosis. Breast ultrasound (US)
      imaging has been proven to be a valuable adjunct to mammography in the detection
      and classification of breast lesions. Because of the fuzzy and noisy nature of
      the US images and the low contrast between the breast cancer and tissue, it is
      difficult to provide an accurate and effective diagnosis. This paper presents a
      novel algorithm based on fuzzy logic that uses both the global and local
      information and has the ability to enhance the fine details of the US images
      while avoiding noise amplification and overenhancement. We normalize the images
      and then fuzzify the normalized images based on the maximum entropy principle.
      Edge and textural information are extracted to describe the lesion features and
      the scattering phenomenon of US images and the contrast ratio measuring the
      degree of enhancement is computed and modified. The defuzzification process is
      used to obtain the enhanced US images. To demonstrate the performance of the
      proposed approach, the algorithm was tested on 86 breast US images. Experimental
      results confirm that the proposed method can effectively enhance the details of
      the breast lesions without overenhancement or underenhancement.

PMID- 16464670
TI  - An anthropomorphic tissue-mimicking phantom of the oesophagus for endoscopic
      ultrasound.
AB  - This study details the design and construct of an anthropomorphic phantom of the
      oesophagus suitable for use with endoscopic ultrasound (EUS) and 3-D volume
      measurements. The phantom was constructed using agar-based tissue-mimicking
      material (TMM) of different acoustical properties to simulate various anatomical
      and pathologic features. The acoustical properties were measured with a scanning
      acoustical macroscope. An Olympus GF-UM200 echo-endoscope and digital position
      measurement arm were used to scan the phantom at 7.5 and 12 MHz. Comparative
      dimensional measurements were performed on the phantom via 2-D and 3-D EUS. TMM
      attenuation varied between 0.1 and 0.5 dB/cm.MHz. Backscatter power, relative to
      normal TMM, was from 0 to -12.2 dB, with an average speed of sound of 1537 +/-
      1.9 m/s. Measurements of objects within the phantom by 2-D and 3-D EUS had mean
      errors of 8% and 2.2%, respectively. The construction of the anthropomorphic EUS
      phantom facilitated EUS training and research and development studies.

PMID- 16464671
TI  - Stability of heterogeneous elastography phantoms made from oil dispersions in
      aqueous gels.
AB  - A set of five tissue-mimicking phantoms with cylindrical inclusions were produced
      for assessing long-term stability of geometry and elastic properties and
      assessing accuracy of determination of elastic properties. The base aqueous
      materials were either gelatin or a mixture of agar and gelatin. Stiffness was
      controlled by selection of the volume percent consisting of microscopic safflower
      oil droplets. Cylinder diameters remained unchanged within 1% or 2% over many
      months. Strain ratios from elastograms of the phantoms were stable over many
      months, implying that elastic contrasts were also stable. Test samples, called
      production samples, for measurement of Young's moduli were made at the time of
      manufacture of each phantom and were stored separately from one another. Each
      production sample was homogeneous and consisted of either inclusion material or
      background material. For all five phantoms, it was found that the elastic
      contrast computed using Young's modulus values determined using the production
      samples accurately represented the true elastic contrasts in the corresponding
      phantom. This finding was established by the fact that the (true) elastic
      contrasts determined using samples excised from the phantoms themselves agreed
      with the elastic contrasts obtained using the homogeneous production samples.

PMID- 16464672
TI  - Pressure field of rectangular transducers at finite amplitude in three
      dimensions.
AB  - In this study, the nonlinear pressure fields of various sized rectangular
      transducers are modeled in three dimensions. The model was based on Aanonsen's
      model, which has earlier been presented for circular sources. The nonlinear wave
      propagation at finite amplitude is presented for square and rectangular type
      sources up to three harmonics. Numerical results are also tested using available
      experimental measurements on the acoustic axis. Good agreement is shown with the
      experiment for both square and rectangular cases.

PMID- 16464673
TI  - Inertial cavitation dose produced in ex vivo rabbit ear arteries with Optison by
      1-MHz pulsed ultrasound.
AB  - Previous in vitro studies have shown that ultrasound-induced mechanical
      bioeffects with contrast agents present are highly correlated with inertial
      cavitation (IC) "dose" (Chen et al. 2003a, 2003c). The ex vivo experiments
      conducted here addressed the following hypotheses: 1. IC activity can be
      generated by insonating perfused rabbit ear blood vessel, and 2. the IC "dose"
      developed during insonation treatment can be reliably measured and will vary with
      varying acoustic parameters and Optison concentration. Ex vivo rabbit auricular
      arteries were perfused with Optison suspensions and then exposed to 1.1-MHz
      pulsed focused ultrasound. Experimental variables included peak negative acoustic
      pressure (0.2 MPa to 5.2 MPa), pulse-repetition frequency (5, 50 or 500 Hz),
      pulse length (50, 100, 500 or 1000 cycles), and Optison volume concentration (0,
      0.2, 0.5 or 1%). Cavitation activity was quantified as IC dose, based on passive
      cavitation detection measurements. The results show that: 1. The IC pressure
      threshold decreases with higher concentrations of Optison, and 2. IC dose
      increases significantly with increasing acoustic pressure, Optison concentration,
      pulse length or with decreasing pulse-repetition frequency.

PMID- 16464674
TI  - Fluorescein isothiocynate-dextran uptake by chinese hamster ovary cells in a 1.5
      MHz ultrasonic standing wave in the presence of contrast agent.
AB  - Uptake of fluorescein isothiocynate-dextran (FITC-dextran) by Chinese hamster
      ovary cells was studied after exposure to ultrasonic standing wave (USW) in
      presence of Optison, an ultrasound contrast agent. Confluent Chinese hamster
      ovary cells were harvested and suspended in phosphate-buffered saline + 0.1%
      bovine serum albumin containing FITC-dextran (10, 40, and 500 kDa) at 10 microM
      final concentration. The suspension was seeded with contrast agent (75 microL/mL)
      and exposed to a 1.5 MHz USW system at acoustic pressures ranging from 0.98 to
      4.2 MPa. Macromolecular uptake was assessed by fluorescent microscopy and
      quantified by flow cytometry 10 min after exposure. FITC-dextran positive cells,
      as assessed by flow cytometry, were 1 +/- 0.05% and 2.58 +/- 0.27% for acoustic
      pressures of 1.96 and 4.2 MPa, respectively (p = 0.006). Fluorescent microscopy
      indicated a degree of macromolecular loading at 0.98 MPa with 46% of peripherally
      FITC-dextran- and/or propidium iodide-stained cells coincident with the
      appearance of significant frequency (f0/2 and 2 f0) emission signals. At higher
      pressures, high macromolecular loading with 6% peripherally stained cells at 1.96
      MPa was associated with lower order emission signals and white noise. The study
      conclusively demonstrates macromolecular loading in an USW, a significantly
      higher macromolecular loading at higher pressures and indicates potential of
      emission signals for a feedback loop to control the acoustic power outputs and
      fine-tune the biologic effects associated with sonoporation.

PMID- 16464675
TI  - Ultrasound exposure can increase the membrane permeability of human neutrophil
      granulocytes containing microbubbles without causing complete cell destruction.
AB  - Activated polymorphonuclear neutrophil (PMN) granulocytes can bind and
      subsequently phagocytose microbubbles used as ultrasound (US) contrast agents.
      The purpose of the present study was to assess insonation effects on cell
      membrane integrity and metabolic activity of activated PMN. Furthermore, we
      investigated whether or not there is an acoustic threshold at which insonation of
      PMN results in increase of membrane permeability without causing complete cell
      destruction. PMN isolated from healthy volunteers were activated with phorbol
      myristate acetate (PMA) for 15 min to allow phagocytosis of albumin and lipid
      microbubbles and were subsequently exposed to US with a mechanical index between
      0.15 and 1.8. Apoptosis, loss of membrane integrity and formation of cell
      fragments were evaluated by measurement of lactate dehydrogenase leakage and by
      double staining with annexin V and propidium iodide, using flow cytometry.
      Neutrophil superoxide anion generation was measured photometrically. Insonation
      of activated PMN in the presence of microbubbles amplified apoptosis and lactate
      dehydrogenase leakage and induced loss of membrane integrity and complete cell
      destruction with increasing acoustic pressures. The bioeffects observed by
      insonation with high mechanical indices (1.0 to 1.8), and particularly the
      formation of cell fragments, were significantly more pronounced in the presence
      of albumin microbubbles. Insonation in the presence of lipid microbubbles
      increased cell membrane permeability, but caused significantly less cell
      destruction and left the metabolic activity of activated PMN uninfluenced. Thus,
      both albumin and lipid microbubbles induce apoptosis and membrane injury during
      insonation of activated PMN. However, insonation in the presence of lipid
      microbubbles seems to influence cell viability to a smaller extent. This could be
      of advantage in the setting of US-guided local drug delivery. In this setting,
      increase of membrane permeability may allow bioactive substances to enter into
      cells, which survive the US treatment, and specifically modify their function.

PMID- 16464680
TI  - Nutritional factors, cognitive decline, and dementia.
AB  - Nutritional factors and nutritional deficiencies have been repeatedly associated
      with cognitive impairment. Most of the evidence is based on cross-sectional
      studies, which cannot prove whether a nutritional deficit is the cause or the
      consequence of an impaired cognitive status. In fact, cognitive impairment, in
      turn, can determine changes in dietary habits and consequent nutritional
      deficiencies. We reviewed clinical and epidemiological studies from January 1983
      to June 2004. Several cross-sectional and fewer prospective studies reported an
      association between dietary or supplemental intake of antioxidants and protection
      from cognitive decline and dementia. There are negative reports as well and some
      methodological biases might have affected the consistencies across studies.
      Deficiencies of several B vitamins have been associated with cognitive
      dysfunction in many observational studies. More recently, deficiencies of folate
      (B9) and cobalamine (B12) have been studied in relation to hyperhomocysteinemia
      as potential determinants of cognitive impairment, dementia, and Alzheimer's
      disease (AD). A small number of studies assessed the association between intake
      of macronutrients and cognitive function or dementia. Among the others, the
      intake of fatty acids and cholesterol has received particular attention. Although
      the results are not always consistent, most studies have reported a protective
      role of dietary intakes of poly- and mono-unsaturated fatty acids against
      cognitive decline and AD. We point out that well designed intervention studies
      are warranted in order to establish specific levels of micro- and macronutrient
      deficiencies and to set general recommendations for the population.

PMID- 16464681
TI  - Evolution of slow-wave sleep and palliopallial connectivity in mammals and birds:
      a hypothesis.
AB  - Mammals and birds are the only animals that exhibit rapid eye-movement (REM)
      sleep and slow-wave sleep (SWS). Whereas the electroencephalogram (EEG) during
      REM sleep resembles the low-amplitude, high-frequency EEG of wakefulness, the EEG
      during SWS displays high-amplitude, slow-waves (1-4Hz). The absence of similar
      slow-waves (SWs) in sleeping reptiles suggests that the neuroanatomical and
      neurophysiological traits necessary for the genesis of SWs evolved independently
      in the mammalian and avian ancestors. Advances in our understanding of
      comparative neuroanatomy and the genesis of mammalian SWs suggest that the
      absence of SWs in reptiles is due to limited connectivity within the pallium, the
      dorsal portion of the telencephalon that includes the mammalian neocortex,
      reptilian dorsal cortex and avian Wulst (hyperpallium), as well as the dorsal
      ventricular ridge in birds and reptiles and the mammalian claustrum and pallial
      amygdala. In mammals, the slow oscillation (<1Hz) of cortical neurons acts
      through reciprocal corticothalamic loops and corticocortical connections to
      synchronize the 1-4Hz activity of thalamocortical neurons in a manner sufficient
      to generate SWs detectable in the EEG. Given the role that corticocortical (or
      palliopallial) connections play in the genesis of SWs in mammals, the degree of
      palliopallial connectivity might explain why birds show SWs and reptiles do not.
      Indeed, whereas the mammalian neocortex and avian pallium show extensive
      palliopallial connectivity, the reptilian pallium exhibits limited intrapallial
      connections. I thus propose that the evolution of SWs is linked to the
      independent evolution of extensive palliopallial connectivity in mammals and
      birds. As suggested by experiments functionally linking SWs to performance
      enhancements, the palliopallial connections that give rise to SWs might also
      depend on SWs to maintain their efficacy.

PMID- 16464682
TI  - Down-regulation of GFRalpha-1 expression by antisense oligodeoxynucleotide
      attenuates electroacupuncture analgesia on heat hyperalgesia in a rat model of
      neuropathic pain.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has been proved to play an
      important role in the modulation of nociceptive transmission especially during
      neuropathic pain. It was reported that electroacupuncture (EA) had potent
      analgesic effect on neuropathic pain and our previous studies indicated that EA
      could activate endogenous GDNF signaling system (GDNF and its receptor GFRalpha
      1) in dorsal root ganglions (DRGs) of neuropathic pain rats. In order to
      investigate whether GDNF signaling system was involved in EA analgesia on
      neuropathic pain, which was induced by chronic constriction injury (CCI) of the
      sciatic nerve in rats, antisense oligodeoxynucleotide (ODN) specifically against
      GFRalpha-1 was used in the present study to result in down-regulation of GFRalpha
      1 expression. The results showed that: (1) cumulative EA had potent analgesic
      effect on neuropathic pain in rats; (2) the expression of GFRalpha-1 in DRGs was
      down-regulated by intrathecal delivery of antisense ODN, but not by normal saline
      (NS) or mismatch ODN; (3) EA analgesia was significantly attenuated by antisense
      ODN treatment. The present study demonstrated that endogenous GDNF signaling
      system was involved in EA analgesia on neuropathic pain in rats, which would
      deepen our realization of the mechanism of EA analgesia.

PMID- 16464683
TI  - HSP70 induction and oxidative stress protection mediated by a subtoxic dose of
      NMDA in the retinoic acid-differentiated C6 glioma cell line.
AB  - NMDA class of glutamate receptors plays an important role in regulating toxic and
      plastic responses in CNS. Astrocytes are the predominant cell type in the adult
      CNS and recent studies have suggested their role in many aspects of CNS function
      and dysfunction. We report here the protective effect of a subtoxic dose of NMDA
      in retinoic acid differentiated C6 glioma cell cultures. C6 glioma cell cultures
      differentiated with retinoic acid (10 microM) were exposed to NMDA (100 microM)
      or to antagonist MK-801 (200 nM) alone as well as with NMDA and cells were
      harvested after 24h of treatment to study the expression of HSP70 and for
      biochemical assay of free radical scavenger system. The protection imparted by a
      subtoxic dose of NMDA was checked by challenging the differentiated controls as
      well as NMDA treated and MK-801 treated cultures with a toxic dose of glutamate
      and subsequently estimating the free radical scavenger system profile.
      Biochemical analysis revealed a significant increase in the activities of
      glutathione peroxidase (GPx), copper zinc-superoxide dismutase (CuZnSOD) and
      reduced glutathione (GSH) content upon exposure to NMDA. No significant change
      was observed in the level of lipid peroxidation (LPx). A significant increase was
      observed in HSP70 expression as seen by Western blotting and
      immunocytofluorescent studies in NMDA treated cultures. Treatment of cultures
      with MK-801 alone, a non-competitive NMDA receptor antagonist, or pretreatment
      with MK-801 prior to NMDA exposure prevented the NMDA mediated changes indicating
      the involvement of NMDA receptors mediated mechanism. The results illustrate the
      protective effect of a subtoxic dose of NMDA in RA differentiated C6 glioma cell
      line.

PMID- 16464685
TI  - Anticonvulsant activity of Harpagophytum procumbens DC [Pedaliaceae] secondary
      root aqueous extract in mice.
AB  - Harpagophytum procumbens DC [family: Pedaliaceae] is widely used in South African
      traditional medicine for the treatment, management and/or control of a variety of
      human ailments. In the present study, we have examined the anticonvulsant
      activity of Harpagophytum procumbens secondary root aqueous extract (HPE, 50-800
      mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline
      (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as
      reference anticonvulsant drugs for comparison. Like the reference anticonvulsant
      agents used, H. procumbens secondary root aqueous extract (HPE, 100-800 mg/kg
      i.p.) significantly (P<0.05-0.001) delayed the onset of, and antagonized,
      pentylenetetrazole (PTZ)-induced seizures. The plant's extract (HPE, 100-800
      mg/kg i.p.) also profoundly antagonized picrotoxin (PCT)-induced seizures, but
      only partially and weakly antagonized bicuculline (BCL)-induced seizures.
      Although the data obtained in the present study do not provide conclusive
      evidence, it would appear that H. procumbens secondary root aqueous extract (HPE)
      produces its anticonvulsant activity by enhancing GABAergic neurotransmission
      and/or facilitating GABAergic action in the brain. In general, the average onset
      of convulsion was delayed, while the average duration of convulsion was markedly
      reduced. The plant's extract also depressed the central nervous system (CNS). It
      is, therefore, thought that the anticonvulsant property of the herb may be
      linked, at least in part, to its ability to depress the central nervous system.
      However, the results of this experimental animal study indicate that H.
      procumbens secondary root aqueous extract possesses anticonvulsant activity, and
      thus lend pharmacological support to the suggested folkloric, ethnomedical uses
      of the plant's extract in the treatment, management and/or control of epilepsy
      and childhood convulsions in some rural communities of South Africa.

PMID- 16464684
TI  - The role of vasopressin in diabetes mellitus-induced hypothalamo-pituitary
      adrenal axis activation: studies in Brattleboro rats.
AB  - Chronic diabetes mellitus (DM) induces hyperactivity of the hypothalamo-pituitary
      adrenal axis (HPA). Our present study addresses the role of vasopressin (AVP) in
      maintaining adrenocortical responsiveness during DM. AVP-deficient mutant
      Brattleboro rats were used with heterozygous controls and the V2 agonist,
      desmopressin was infused to replace peripheral AVP. To induce DM the rats were
      injected by streptozotocin (STZ, 60 mg/ml/kg i.v.) and studied 2 weeks later. The
      acute stress stimulus was 60 min restraint. The signs of DM (the increase in
      water consumption and in blood glucose levels) were discovered in all rats. The
      diuretic effect of the lack of AVP was additional to the DM-induced osmotic
      diuresis. DM induced significant, chronic stress-like somatic changes on which
      AVP-deficiency had no effect and although desmopressin infusion normalized the
      water consumption and the body weight gain in AVP-deficient rats, it had no
      effect on DM-induced changes. The acute stress-induced plasma ACTH elevation was
      smaller in AVP-deficient or DM rats but these effects were not additive.
      Desmopressin did not normalize the decreased ACTH-elevation of AVP-deficient
      animals. The resting morning plasma corticosterone level was elevated both in DM
      and AVP-deficient rats without interaction. The restraint-induced corticosterone
      rise was influenced neither by the lack of AVP nor by DM and the basal and stress
      induced prolactin levels were smaller in DM rats without any effect of AVP
      deficiency. In conclusion, our data suggest that AVP does not play a crucial role
      in HPA axis regulation during DM-induced chronic stress. In contrast, the role of
      AVP seems to be more important during acute stress, however, it is restricted to
      the ACTH regulation. According to the water consumption data diabetes insipidus
      seems to be an additional risk factor for DM.

PMID- 16464686
TI  - Fronto-parietal coupling of brain rhythms in mild cognitive impairment: a
      multicentric EEG study.
AB  - Electroencephalographic (EEG) data were recorded in 69 normal elderly (Nold), 88
      mild cognitive impairment (MCI), and 109 mild Alzheimer's disease (AD) subjects
      at rest condition, to test whether the fronto-parietal coupling of EEG rhythms is
      in line with the hypothesis that MCI can be considered as a pre-clinical stage of
      the disease at group level. Functional coupling was estimated by synchronization
      likelihood of Laplacian-transformed EEG data at electrode pairs, which accounts
      for linear and non-linear components of that coupling. Cortical rhythms of
      interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5
      13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz). Compared to the
      Nold subjects, the AD patients presented a marked reduction of the
      synchronization likelihood (delta to gamma) at both fronto-parietal and inter
      hemispherical (delta to beta 2) electrodes. As a main result, alpha 1
      synchronization likelihood progressively decreased across Nold, MCI, and mild AD
      subjects at midline (Fz-Pz) and right (F4-P4) fronto-parietal electrodes. The
      same was true for the delta synchronization likelihood at right fronto-parietal
      electrodes (F4-P4). For these EEG bands, the synchronization likelihood
      correlated with global cognitive status as measured by the Mini Mental State
      Evaluation. The present results suggest that at group level, fronto-parietal
      coupling of the delta and alpha rhythms progressively becomes abnormal though MCI
      and mild AD. Future longitudinal research should evaluate whether the present EEG
      approach is able to predict the cognitive decline in individual MCI subjects.

PMID- 16464687
TI  - Swimming behaviour and post-swimming activity in Vitamin D receptor knockout
      mice.
AB  - Animal experiments have shown that Vitamin D plays a role in both brain
      development and adult brain function. The adult Vitamin D receptor null mutant
      mouse (VDR -/-) is reported to be less active and more anxious than wild-type
      litter mate controls and to have poor swimming ability. However, an "anxious"
      behavioural phenotype is inferred from differences in locomotor behaviour. This
      is a general problem in behavioural phenotyping where a neurological phenotype is
      inferred from changes in locomotion which will be affected by non-neurological
      factors, such as muscle fatigue. In this study of VDR -/-, we conducted a
      detailed examination of one form of motor behaviour, swimming, compared to
      wildtype littermate controls. Swimming was assessed using a forced swim test, a
      laneway swimming test and a watermaze test using a visible platform. Post
      swimming activity was assessed by comparing grooming and rearing behaviour
      before, and 5 min after, the forced swimming test. We replicated previous
      findings in which VDR -/- mice demonstrate more sinking episodes than wildtype
      controls in the forced swim test but they were similar to controls in the time
      taken to swim a 1m laneway, and in the time taken to reach a visible platform in
      the watermaze. Thus, the VDR -/- mice were able to swim but were not able to
      float. Grooming and rearing behaviour of the VDR -/- mice was similar to wildtype
      controls before the forced swim but the VDR -/- were much less active after the
      swim compared with wildtype mice which displayed high levels of grooming and
      rearing. We conclude that VDR -/- mice have muscular and motor impairments that
      do not affect their ability to swim but significantly alters the ability to float
      as well as their post-swimming activity. Differences in muscle strength may
      confound tests of activity that are used to infer an "anxious" phenotype.

PMID- 16464688
TI  - Phospholipid mass is increased in fibroblasts bearing the Swedish amyloid
      precursor mutation.
AB  - Phospholipid changes occur in brain regions affected by Alzheimer disease (AD),
      including a marked reduction in plasmalogens, which could diminish brain function
      either by directly altering signaling events or by bulk membrane effects.
      However, model systems for studying the dynamics of lipid biosynthesis in AD are
      lacking. To determine if fibroblasts bearing the Swedish amyloid precursor
      protein (swAPP) mutation are a useful model to study the mechanism(s) associated
      with altered phospholipid biosynthesis in AD, we examined the steady-state
      phospholipid mass and composition of fibroblasts, including plasmalogens. We
      found a 15% increase in total phospholipid mass, accounted for by a 24% increase
      in the combined total of phosphatidylethanolamine and plasmanylethanolamine mass
      and a 19% increase in the combined total of phosphatidylcholine (PtdCho) and
      plasmanycholine (PakCho) mass in the swAPP mutant bearing fibroblasts.
      Cholesterol mass was unchanged in these cells. The changes in phospholipid mass
      did not alter the cellular molar composition of the phospholipids nor the
      cholesterol to phospholipid ratio. While plasmalogen mass was not altered, the
      ratio of choline plasmalogen (PlsCho) mass to PtdCho+PakCho mass was decreased
      16% and there was a 14% reduction in the proportion of PlsCho as a percent of
      total phospholipids in the swAPP mutant bearing fibroblasts. This change in
      choline plasmalogen is consistent with the reported decreases in plasmalogen
      proportions in affected regions of AD brain, suggesting that these cells may
      serve as a useful model to determine the mechanism underlying changes in
      plasmalogen biosynthesis in AD brain.

PMID- 16464689
TI  - A direct demonstration of cortical LTP in humans: a combined TMS/EEG study.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is increasingly being used to
      promote cortical reorganization, under the assumption that it can induce long
      term potentiation (LTP) of neural responses. This assumption is supported by
      several lines of indirect evidence. For example, rTMS of motor cortex can induce
      a potentiation of muscle motor evoked potentials that outlasts the stimulation by
      several minutes. In animal models, a direct demonstration of LTP is typically
      obtained by high-frequency electrical stimulation coupled with local field
      recordings of population responses. In this study, we exploited a new approach
      based on combined rTMS/high-density electroencephalography (hd-EEG) to obtain
      direct, noninvasive evidence for LTP in humans. Cortical responses to single TMS
      pulses were measured with hd-EEG before and after applying rTMS to motor cortex
      (5Hz, 1500 pulses). The results demonstrate that, after rTMS, EEG responses at
      latencies of 15-55ms were significantly potentiated. A topographic analysis
      revealed that this potentiation was significant at EEG electrodes located
      bilaterally over premotor cortex. Thus, these findings provide a direct
      demonstration in humans of LTP induced by rTMS.

PMID- 16464690
TI  - Effect of membrane lateral pressure on the expression of fructosyltransferases in
      Lactobacillus reuteri.
AB  - The effect of environmental conditions on the production of homo-polysaccharides
      and oligosaccharides from sucrose and the regulation of glycosyltransferase genes
      responsible for biosynthesis of homo-polysaccharides was determined in
      Lactobacillus reuteri TMW1.106 (reutericyclin-producer) and LTH5448
      (reutericyclin-negative). Strain L. reuteri TMW 1.106 harbours the
      glycosyltransferase genes gtfA and inu, strain LTH5448 harbours a
      fructosyltransferase, ftfA. Fructan and fructose-oligosaccharide (FOS) production
      in both strains was inducible by reutericyclin, trans-isohumulone, and nigericin
      at the levels of their minimum inhibitory concentrations (MIC) as well as
      phenylethanol (6mM) and elevated growth temperatures (45 degrees C), but not by
      nisin, CCCP or gramicidin. Elevated temperature (45 degrees C), reutericyclin or
      trans-isohumulone but not CCCP furthermore increased enhanced inu and ftfA
      transcription in L. reuteri TMW1.106 and LTH5448, respectively. Generally,
      effects of the various agents on fructosyltransferase transcription corresponded
      to their effect on formation of poly and oligosaccharides from sucrose. The
      effect of membrane-active agents on fructosyltransferase expression was compared
      to their effect on membrane biophysical parameters. The ability of chemical and
      physical agents to induce expression of fructosyltransferases correlated to their
      effect on the membrane lateral pressure as measured by pyrene-labelled
      phospholipids in membrane vesicles. Dextran, levan and fructose-oligosaccharides
      added at 50gL(-1) protected L. reuteri towards the membrane-active inhibitors
      nisin, reutericyclin, and CCCP. The induction of glycosyltransferases by membrane
      stress indicates a protective role of fructans and FOS to lactobacilli exposed to
      physical and chemical environmental stressors.

PMID- 16464691
TI  - Chimaereicella alkaliphila gen. nov., sp. nov., a Gram-negative alkaliphilic
      bacterium isolated from a nonsaline alkaline groundwater.
AB  - A Gram-negative bacterium designated AC-74(T) was isolated from a highly alkaline
      groundwater environment (pH 11.4). This organism formed rod-shaped cells, is
      strictly aerobic, catalase and oxidase positive, tolerates up to 3.0% NaCl, has
      an optimum growth temperature of 30 degrees C, but no growth occurs at 10 or 40
      degrees C, and an optimum pH value of 8.0, but no growth occurs at pH 7.0 or
      11.3. The predominant fatty acids are iso-15:0, iso-17:1 omega9c and 16:1 omega7c
      and or iso-15:2OH. The G+C content of DNA was 43.5mol%. The phylogenetic analyses
      of the sequences of the 16s RNA genes indicated that strain AC-74(T) belongs to
      the family "Flexibacteriaceae" and is phylogenetically equidistant (
      approximately 94.5%) from the majority of the species of the genus Algoriphagus
      and from the genus Hongiella. Based on the phylogenetic analyses and distinct
      phenotypic characteristics, we are of the opinion that strain AC-74(T),
      represents a new species of the novel genus for which we propose the name
      Chimaereicella alkaliphila gen. nov., sp. nov.

PMID- 16464692
TI  - Genetic diversity and pathogenicity of the grass pathogen Xanthomonas translucens
      pv. graminis.
AB  - Genetic diversity of Xanthomonas translucens pv. graminis (X.t.g.), the causal
      agent of bacterial wilt in forage grasses, was assessed using 16S rDNA
      sequencing, AFLP analysis and pathogenicity screening on three Italian ryegrass
      (Lolium multiflorum) cultivars. The aim of this in depth analysis was to provide
      insight into geographic variation and race specificity of X.t.g. in order to
      develop strategies for plant protection and resistance breeding. 16S rDNA
      sequencing of 29 putative X.t.g. isolates allowed to assign 28 isolates to the
      pv. translucens while one isolate was identified as X.t. pv. arrhenatheri. AFLP
      analysis and UPGMA clustering resulted in two distinct clusters with a similarity
      of 90% based on Nei and Li's coefficient and 306 polymorphic markers. A
      significant effect of geographic location of the collection sites on genetic
      diversity was detected by redundancy analysis using AFLP markers and the
      explanatory variables longitude, latitude and altitude. The two groups identified
      with redundancy analysis were congruent to the major clusters identified with
      cluster analysis. All X.t.g. isolates identified as pv. graminis were pathogenic,
      showing mostly moderate to high pathogenicity. However, the three cultivars used
      for pathogenicity testing showed significant differences in susceptibility and a
      significant interaction between cultivars and isolates was observed, indicating
      an at least partial race-specific resistance. With the information provided,
      targeted selection of X.t.g. isolates may allow one to efficiently address
      specific tasks in resistance breeding.

PMID- 16464693
TI  - Genotypic and phenotypic characterization of fusobacteria from Chinese and
      European patients with inflammatory periodontal diseases.
AB  - Phylogenetic and antigenic studies were performed on 48 human oral Fusobacterium
      strains from Chinese patients with either necrotizing ulcerative gingivitis (NUG)
      or gingivitis and on 23 Fusobacterium nucleatum or Fusobacterium periodonticum
      strains from European periodontitis patients. Alignment of partial 16S rRNA gene
      sequences resulted in a phylogenetic tree that corresponded well with the current
      classification of oral fusobacteria into F. periodonticum and several subspecies
      of F. nucleatum, in spite of much minor genetic variability. F. periodonticum, F.
      nucleatum subsp. animalis and a previously undescribed phylogenetic cluster (C4),
      that may represent an additional F. nucleatum subspecies, constituted discrete
      clusters distinct from the remainder of F. nucleatum with high bootstrap values.
      Chinese and European strains differed markedly with regard to their respective
      classification patterns, suggesting a predominance of F. peridonticum and F.
      nucleatum susp. animalis over F. nucleatum subsp. nucleatum and F. nucleatum
      subsp. fusiforme/vincentii in samples from China. Antigenic typing enabled the
      association of many previously described serovars with distinct phylogenetic
      clusters and when applied directly to uncultured clinical samples confirmed the
      differential distribution of oral Fusobacterium taxa in Chinese and European
      samples. Bacteria from cluster C4 and F. nucleatum subsp. animalis were
      significantly more prevalent and accounted for higher cell numbers in NUG than in
      gingivitis samples, suggesting a possible association of these rarely observed
      taxa with NUG in Chinese patients.

PMID- 16464694
TI  - Random amplification of polymorphic DNA (RAPD) typing of carnobacteria isolated
      from hindgut chamber and large intestine of Atlantic cod (Gadus morhua l.).
AB  - Autochthonous and allochthonous bacteria were isolated from hindgut chamber and
      large intestine of fed and starved Atlantic cod (Gadus morhua L.). All bacterial
      strains isolated from hindgut chamber belong to carnobacteria. However, only
      10.2% of the bacteria strains from the large intestine belong to carnobacteria.
      Random amplification of polymorphic DNA (RAPD) analysis using three selective
      primers, was performed to further identify the carnobacteria strains. Nine of
      these were isolated from hindgut chamber contents, ten associated with epithelial
      cells of the hindgut chamber, and six isolated from the large intestines of fed
      and starved fish. The 25 isolates segregated into eight clusters. The major
      cluster comprised nine strains isolated from the hindgut chamber of both fed and
      starved fish showing low similarity with the reference strains. The other strains
      isolated from the hindgut were located in clusters showing high similarity with
      Carnobacterium gallinarum or Carnobacterium piscicola. Strains isolated from
      large intestine appeared more divergent and were located in five different
      clusters. Autochthonous (indigenous) bacteria were clearly demonstrated in the
      hindgut chamber as transmission electron microscopy revealed rod-shaped bacteria
      between adjacent microvilli. Endocytosis of bacteria by epithelial cells was
      observed in the hindgut chamber.

PMID- 16464695
TI  - Molecular characterization of lactic acid bacteria from sourdough breads produced
      in Sardinia (Italy) and multivariate statistical analyses of results.
AB  - The objective of this work was to investigate the structure and diversity of
      lactic acid bacteria (LAB) communities in sourdough used for the production of
      traditional breads (Carasau, Moddizzosu, Spianata, Zichi) in Sardinia. 16S rDNA
      sequencing and Randomly Amplified Polymorphic DNA (RAPD-PCR) was applied for the
      identification and typing of the LAB isolated from 25 samples of sourdoughs.
      Multivariate statistical techniques were applied to RAPD-PCR pattern to study the
      biological diversity of sourdough samples. Twelve different species of LAB were
      identified, and most isolates were classified as facultative heterofermentative
      lactobacilli. Lactobacillus pentosus dominated the lactic microflora of many
      samples while Lactobacillus sanfranciscensis was isolated only from a limited
      number of samples. Although heterofermentative species represented between
      between 30% and 60% of the isolates in Carasau, Spianata and Zichi sourdoughs,
      only 2% of the isolates from Moddizzosu sourdoughs were identified as
      heterofermentative LAB. RAPD-PCR with a single primer followed by cluster
      analysis did not allow the identification of the isolates at the species level.
      However, a multidimensional scaling/bootstrapping approach on the RAPD-PCR
      patterns uncovered the diversity of the LAB communities of LAB showing
      differences both within and between bread types.

PMID- 16464697
TI  - Occurrence of toxigenic cyanobacterial blooms in freshwaters of Sri Lanka.
AB  - A previous pioneering study of freshwater bodies in Sri Lanka revealed the
      presence of toxic cyanobacteria in three out of four water bodies tested. It was
      therefore important to perform a more detailed investigation into the presence of
      cyanobacteria and their toxins throughout Sri Lanka. The country has a long
      history of well-planned water management with the agricultural economy and
      drinking water supply still dependent on thousands of man-made tanks. Seventeen
      reservoirs from different user categories and different climatic zones were
      selected to study variations in phytoplankton communities with relation to major
      nutrients, with particular emphasis on cyanobacteria. The study was carried out
      during a two-year period and heavy growths or blooms of cyanobacteria observed
      during the study period were tested for microcystins. The results clearly
      categorised the 17 reservoirs into four groups parallel to the classification
      based on the user categories of water bodies. Biomass of total phytoplankton, the
      abundance of cyanobacteria, the dominance of Microcystis spp. and concentration
      of nitrate (N) and total phosphorous (P) were the lowest in drinking water bodies
      and the highest in aesthetic water bodies. Irrigation water bodies showed the
      second lowest values for phytoplankton biomass, and concentration of N and P,
      while hydropower reservoirs showed the second highest values for the same
      parameters. The fraction of cyanobacteria in irrigation waters was higher than
      that in hydropower reservoirs, but surprisingly the dominance of Microcystis spp.
      was reversed. Possible reasons for these variations are discussed. More than half
      of the bloom material tested contained microcystins up to 81microgl(-1). Our
      findings indicate the potential for high-risk situations due to toxigenic
      cyanobacterial blooms in susceptible freshwaters of Sri Lanka.

PMID- 16464696
TI  - Antibiotic susceptibility patterns and resistance genes of starter cultures and
      probiotic bacteria used in food.
AB  - A survey of starter and probiotic cultures was carried out to determine the
      current antibiotic resistance situation in microbial food additives in
      Switzerland. Two hundred isolates from 90 different sources were typed by
      molecular and other methods to belong to the genera Lactobacillus (74 samples),
      Staphylococcus (33 samples), Bifidobacterium (6 samples), Pediococcus (5
      samples), or were categorized as lactococci or streptococci (82 samples). They
      were screened for phenotypic resistances to 20 antibiotics by the disk diffusion
      method. Twenty-seven isolates exhibiting resistances that are not an intrinsic
      feature of the respective genera were further analyzed by microarray
      hybridization as a tool to trace back phenotypic resistances to specific genetic
      determinants. Their presence was finally verified by PCR amplification or
      Southern hybridization. These studies resulted in the detection of the
      tetracycline resistance gene tet(K) in 5 Staphylococcus isolates used as meat
      starter cultures, the tetracycline resistance gene tet(W) in the probiotic
      cultures Bifidobacterium lactis DSM 10140 and Lactobacillus reuteri SD 2112
      (residing on a plasmid), and the lincosamide resistance gene lnu(A) (formerly
      linA) in L. reuteri SD 2112.

PMID- 16464698
TI  - Biochemical evidence for the proteolytic degradation of infectious prion protein
      PrPsc in hamster brain homogenates by foodborne bacteria.
AB  - PrP(Sc) is a general term to describe the infectious agent causing transmissible
      spongiform encephalopathy (TSE), and the protease-resistant form of cellular
      PrP(C). In this study, we have identified several protease-secreting bacteria
      able to degrade PrP(Sc) under more or less native conditions (30 degrees C, pH
      8), focusing on strains isolated mainly from cheese. One hundred and ninty-nine
      protease-secreting isolates belonging to the Actinomycetales and Bacillales were
      screened for the expression of PrP(Sc) degrading activity by a Western blot
      procedure. Only 6 strains belonging to the following species were found to
      exhibit such an activity: Arthrobacter nicotianae, Bacillus licheniformis,
      Brachybacterium conglomeratum, Brachybacterium tyrofermentans and Staphylococcus
      sciuri and Serratia spp. As revealed by a general protease assay based on dye
      labeled Azocoll substrate, the PrP(Sc) degrading activity was not directly
      correlated to the total level of secreted proteolytic activity of these
      organisms. This indicates that specific proteases are required for the
      degradation of PrP(Sc). Our study also suggests the potential use of such starter
      bacteria or their proteases for application in PrP(Sc) degradation and
      decontamination under native conditions.

PMID- 16464699
TI  - Application of SSCP-PCR fingerprinting to profile the yeast community in raw milk
      Salers cheeses.
AB  - Bacteria and yeasts are important sensory factors of raw-milk cheeses as they
      contribute to the sensory richness and diversity of these products. The diversity
      and succession of yeast populations in three traditional Registered Designation
      of Origin (R.D.O.) Salers cheeses have been determined by using phenotypic
      diagnoses and Single-Strand Conformation Polymorphism (SSCP) analysis. Isolates
      were identified by phenotypic tests and the sequencing of the D1-D2 domains of
      the 26S rRNA gene. Ninety-two percent of the isolates were identified as the same
      species in both tests. Yeast-specific primers were designed to amplify the V4
      region of the 18S rRNA gene for SSCP analysis. The yeast species most frequently
      encountered in the three cheeses were Kluyveromyces lactis, Kluyveromyces
      marxianus, Saccharomyces cerevisiae, Candida zeylanoides and Debaryomyces
      hansenii. Detection of less common species, including Candida parapsilosis,
      Candida silvae, Candida intermedia, Candida rugosa, Saccharomyces unisporus, and
      Pichia guilliermondii was more efficient with the conventional method. SSCP
      analysis was accurate and could be used to rapidly assess the proportions and
      dynamics of the various species during cheese ripening. Each cheese was clearly
      distinguished by its own microbial community dynamics.

PMID- 16464700
TI  - Neck-focused panic attacks among Cambodian refugees; a logistic and linear
      regression analysis.
AB  - Consecutive Cambodian refugees attending a psychiatric clinic were assessed for
      the presence and severity of current--i.e., at least one episode in the last
      month--neck-focused panic. Among the whole sample (N=130), in a logistic
      regression analysis, the Anxiety Sensitivity Index (ASI; odds ratio=3.70) and the
      Clinician-Administered PTSD Scale (CAPS; odds ratio=2.61) significantly predicted
      the presence of current neck panic (NP). Among the neck panic patients (N=60), in
      the linear regression analysis, NP severity was significantly predicted by NP
      associated flashbacks (beta=.42), NP-associated catastrophic cognitions
      (beta=.22), and CAPS score (beta=.28). Further analysis revealed the effect of
      the CAPS score to be significantly mediated (Sobel test [Baron, R. M., & Kenny,
      D. A. (1986). The moderator-mediator variable distinction in social psychological
      research: conceptual, strategic, and statistical considerations. Journal of
      Personality and Social Psychology, 51, 1173-1182]) by both NP-associated
      flashbacks and catastrophic cognitions. In the care of traumatized Cambodian
      refugees, NP severity, as well as NP-associated flashbacks and catastrophic
      cognitions, should be specifically assessed and treated.

PMID- 16464701
TI  - The psychometric properties of the MASC in a pediatric psychiatric sample.
AB  - The goals of this study were twofold: to examine the psychometric properties of
      the Multidimensional Anxiety Scale for Children (MASC) in a clinical sample of
      193 children and adolescents who had received a diagnosis of major depressive or
      anxiety disorder, and to discriminate between these two groups of patients.
      Participants had volunteered in randomized psychopharmacological clinical trials.
      The MASC four-factor structure was confirmed and its subscales were found to be
      reliable. The MASC correlated well with other self-report measures of anxiety,
      and less so with measures of depressive symptoms. The MASC subscales and two MASC
      items as well as age differentiated between anxious and depressed pediatric
      patients. If these results are replicated in an independent study, those items
      could be used by clinicians to discriminate between these two disorders. The MASC
      is a clinically useful measure to discriminate between anxious and depressed
      pediatric patients. Limitations due to the highly selective sample are noted.

PMID- 16464702
TI  - A comparison of intolerance of uncertainty in analogue obsessive-compulsive
      disorder and generalized anxiety disorder.
AB  - Intolerance of uncertainty has been defined as the unwillingness to tolerate the
      possibility that negative events may occur in the future, no matter how low the
      probability [Personality Individual Differences 17 (1994), 791-802]. Previous
      research suggests that intolerance of uncertainty may be more specific to worry
      and generalized anxiety disorder (GAD) than to other anxiety disorders [e.g.,
      Dugas, M. J., Buhr, K., & Ladouceur, R. (2004). The role of intolerance of
      uncertainty in the etiology and maintenance of generalized anxiety disorder. In
      R. G. Heimberg, C. L. Turk, & D. S. Mennin (Eds.), Generalized anxiety disorder:
      Advances in research and practice (pp. 143-163). New York: Guilford Press].
      However, Tolin et al. [J. Anxiety Disorders 17 (2003), 233-242] argued that
      intolerance of uncertainty may also play a central role in obsessive-compulsive
      disorder (OCD). Therefore, the current study compared intolerance of uncertainty
      in individuals with analogue GAD and/or OCD. Intolerance of uncertainty was
      strongly related to pathological worry, GAD symptoms, and OCD symptoms; however,
      neither worry nor GAD was found to be more strongly associated with intolerance
      of uncertainty than OCD. Further, individuals with analogue GAD or OCD reported
      more intolerance of uncertainty than controls, but they did not differ
      significantly from each other. These findings suggest that intolerance of
      uncertainty may be a central theme in a number of the anxiety disorders.

PMID- 16464703
TI  - Efficacy of three treatment protocols for adolescents with social anxiety
      disorder: a 5-year follow-up assessment.
AB  - Few studies have reported long-term follow-up data in adults and even fewer in
      adolescents. The purpose of this work is to report on the longest follow-up
      assessment in the literature on treatments for adolescents with social phobia. A
      5-year follow-up assessment was conducted with subjects who originally received
      either Cognitive Behavioral Group Therapy for Adolescents (CBGT-A), Social
      Effectiveness Therapy for Adolescents--Spanish version (SET-Asv), or Intervencion
      en Adolescentes con Fobia Social--Treatment for Adolescents with Social Phobia
      (IAFS) in a controlled clinical trial. Twenty-three subjects completing the
      treatment conditions were available for the 5-year follow-up. Results demonstrate
      that subjects treated either with CBGT-A, SET-Asv and IAFS continued to maintain
      their gains after treatments were terminated. Either the CBGT-A, SET-Asv and IAFS
      can provide lasting effects to the majority of adolescents with social anxiety.
      Issues that may contribute to future research and clinical implications are
      discussed.

PMID- 16464704
TI  - Affect intensity: association with anxious and fearful responding to bodily
      sensations.
AB  - The present investigation evaluated affect intensity in regard to anxious and
      fearful responding to a voluntary hyperventilation paradigm. Participants were 90
      young adults without a history of Axis I psychopathology or nonclinical panic
      attacks. The incremental validity of affect intensity was examined relative to
      gender, negative affectivity, anxiety sensitivity, and anticipatory anxiety. As
      hypothesized, affect intensity significantly and incrementally predicted the
      perceived intensity of post-challenge panic-relevant physical and cognitive
      symptoms but not physiological arousal. Findings are discussed in relation to
      better understanding the role of affect intensity as a potential risk factor for
      panic-related problems.

PMID- 16464705
TI  - No distinctions between different types of anxiety symptoms in pre-adolescents
      from the general population.
AB  - Studies aimed at anxiety symptoms in children from the general population samples
      often make distinctions between symptoms of Separation Anxiety, Social Phobia,
      Panic Disorder, and Generalized Anxiety Disorder. Given the high comorbidity
      rates between these disorders, the usefulness of such distinctions is
      questionable. The present study was conducted to investigate which homogenous
      subgroups of children aged 10-12 years can be identified, according to the
      presence and frequencies of different types of anxiety. A general population
      sample of 2210 children was assessed with the RCADS, a self-report questionnaire.
      Latent class analysis did not yield classes of children with symptoms of one
      anxiety disorder, without symptoms of another anxiety disorder. Instead, five
      classes of children were identified that differed in the frequency of anxiety
      symptoms, irrespective of the type of anxiety. Results indicate that, in a
      general population sample, it may not be useful to discern children with
      different types of anxiety symptoms.

PMID- 16464706
TI  - Investigating the construct validity of intolerance of uncertainty and its unique
      relationship with worry.
AB  - Although recent findings suggest that intolerance of uncertainty is a fundamental
      construct involved in excessive worry, additional research is required to further
      establish the construct validity of intolerance of uncertainty and demonstrate
      its unique contribution to the understanding of worry. The present study examined
      the relationships among measures of worry, intolerance of uncertainty,
      intolerance of ambiguity, perfectionism, and perceived control in a sample of 197
      university students. The findings indicated that intolerance of uncertainty
      moderately overlaps with earlier conceptualizations of intolerance of ambiguity;
      however, worry was more highly related to intolerance of uncertainty than to
      intolerance of ambiguity. Intolerance of uncertainty also emerged as the most
      salient predictor of worry compared to other cognitive processes such as
      perfectionism and perceived control. Worry and intolerance of uncertainty
      continued to be significantly related after controlling for intolerance of
      ambiguity, perfectionism, and perceived control, which implies that intolerance
      of uncertainty shares a unique association with worry that is not accounted for
      by these other cognitive factors. Overall, the findings provide evidence of
      construct validity and underscore the role of intolerance of uncertainty in the
      conceptualization of worry.

PMID- 16464707
TI  - Modification of the Body Sensations Interpretation Questionnaire (BSIQ-M):
      validity and reliability.
AB  - The catastrophic misinterpretation model [Behav. Res. Ther. 24 (1986) 461-470]
      proposes that panic attacks result from misinterpretation of interoceptive
      stimuli as precursors to physical or psychological emergency. Inconclusive
      evidence for the model may be partly explained by limitations of the
      questionnaires developed to measure catastrophic misinterpretation. For example,
      the Body Sensations Interpretation Questionnaire (BSIQ) is unable to clarify
      whether anxiety-related interpretations of ambiguous interoceptive stimuli
      represent catastrophic misinterpretations or responses masking feared outcomes
      (e.g., heart failure). Additionally, it lacks items relating to several DSM-IV
      criteria for panic, thereby limiting content validity. Reliability is also
      potentially compromised due to experimenter-coding of participant-generated
      responses. A modified form of the BSIQ was developed to address these limitations
      and evaluated with non-anxious controls (n=34) and people with panic disorder
      (n=38). The revised questionnaire demonstrated good to excellent internal
      consistency, inter-rater reliability, and construct validity and is a useful
      development of the BSIQ.

PMID- 16464708
TI  - Anxiety, depression, and judgments about the probability of future negative and
      positive events in children.
AB  - Probability bias refers to the phenomenon that high-anxious individuals estimate
      future negative events as far more likely to occur, and in particular to
      themselves, than low-anxious individuals. The present study further examined this
      cognitive bias in a sample of non-clinical children aged between 10 and 13 years.
      Participants completed a scale for measuring symptoms of DSM-defined anxiety
      disorders and major depressive disorder, and a modified version of the Subjective
      Probability Questionnaire in order to assess probability estimates of future
      negative and positive events. Results showed that children's anxiety and
      depression symptoms were positively associated with probability estimates of
      future negative events, but only when these events referred to children
      themselves. Further, when controlling for concurrent depression symptoms, anxiety
      remained significantly linked to probability ratings of self-referent negative
      events. When controlling for concurrent anxiety symptoms, depression was no
      longer linked to probability estimates of negative events. Finally, depression
      symptoms were negatively related to probability ratings for future positive
      events.

PMID- 16464709
TI  - The status of nuclear cardiology today.

PMID- 16464710
TI  - Should PET replace SPECT for evaluating CAD? The end of the beginning.

PMID- 16464711
TI  - I-123 metaiodobenzylguanidine imaging in non-insulin-dependent diabetic patients
      with normal myocardial perfusion scans: new insights into their increased cardiac
      morbidity and mortality rates.

PMID- 16464712
TI  - Screening of asymptomatic patients with type 2 diabetes mellitus for silent
      coronary artery disease: combined use of stress myocardial perfusion imaging and
      coronary calcium scoring.
AB  - Diabetes mellitus and coronary artery disease constitute an ominous clinical
      combination. Rates of morbidity and mortality as a result of cardiovascular
      complications are high in patients with type 2 diabetes mellitus. Screening for
      silent coronary artery disease, to detect the disease in an early stage and to be
      able to initiate early appropriate treatment, has recently become an important
      focus of clinical investigation. Recent prospective studies have shown that the
      overall prevalence of silent coronary artery disease in truly asymptomatic
      individuals with diabetes is about 20% to 25%. It is of practical and clinical
      importance to explore ways to "enrich" the target screening population. In this
      editorial point of view the relative roles of stress radionuclide myocardial
      perfusion imaging and coronary calcium scoring are examined. The two
      methodologies appear to have complementary values for the screening of
      asymptomatic individuals with diabetes mellitus. A screening algorithm involving
      sequential use of coronary calcium scoring and subsequent stress radionuclide
      myocardial perfusion imaging is proposed.

PMID- 16464713
TI  - Issues regarding radiation dosage of cardiac nuclear and radiography procedures.

PMID- 16464714
TI  - Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET:
      comparison with ECG-gated Tc-99m sestamibi SPECT.
AB  - BACKGROUND: Although single photon emission computed tomography (SPECT) and
      positron emission tomography (PET) myocardial perfusion imaging (MPI) have
      evolved considerably over the last decade, there is no recent comparison of
      diagnostic performance. This study was designed to assess relative image quality,
      interpretive confidence, and diagnostic accuracy by use of contemporary
      technology and protocols. METHODS AND RESULTS: By consensus and without clinical
      information, 4 experienced nuclear cardiologists interpreted 112 SPECT technetium
      99m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)-gated
      rest/pharmacologic stress studies in patient populations matched by gender, body
      mass index, and presence and extent of coronary disease. The patients were
      categorized as having a low likelihood for coronary artery disease (27 in each
      group) or had coronary angiography within 60 days. SPECT scans were acquired on a
      Cardio-60 system and PET scans on an ECAT ACCEL scanner. Image quality was
      excellent for 78% and 79% of rest and stress PET scans, respectively, versus 62%
      and 62% of respective SPECT scans (both p<.05). An equal percent of PET and SPECT
      gated images were rated excellent in quality. Interpretations were definitely
      normal or abnormal for 96% of PET scans versus 81% of SPECT scans (p=.001).
      Diagnostic accuracy was higher for PET for both stenosis severity thresholds of
      70% (89% vs 79%, p=.03) and 50% (87% vs 71%, p=.003) and was higher in men and
      women, in obese and nonobese patients, and for correct identification of
      multivessel coronary artery disease. CONCLUSION: In a large population of matched
      pharmacologic stress patients, myocardial perfusion PET was superior to SPECT in
      image quality, interpretive certainty, and diagnostic accuracy.

PMID- 16464716
TI  - Automated quality control of emission-transmission misalignment for attenuation
      correction in myocardial perfusion imaging with SPECT-CT systems.
AB  - BACKGROUND: Emission-transmission misalignment with single-photon emission
      computed tomography (SPECT)-computed tomography (CT) systems can impair
      attenuation correction (AC) in myocardial perfusion imaging. This study was
      performed to develop automated quality control (Auto-QC) to detect critical
      misalignment that can significantly impact AC. METHODS AND RESULTS: Auto-QC was
      developed to segment myocardium and mediastinum from emission and transmission
      reconstructions, respectively. Myocardium-mediastinum mismatch was used as the
      quality-control index (QCI). The QCI threshold for acceptable AC was determined
      with NCAT (NURBS [nonuniform rational B-spline]-based cardiac torso phantom)
      simulation and verified with 2 patients with minimal misalignment. Compromised
      data sets, generated by shifting the attenuation maps by 0.5, 1.0, 1.5, and 2.0
      pixels along left-right, up-down, and head-foot directions, respectively, were
      qualitatively and quantitatively compared with the unshifted data sets. Auto-QC
      was tested with the 2 verification patients and 41 additional patients. Shifts by
      more than 1 pixel along any direction compromised AC. Auto-QC with the QCI
      threshold (3%) had highly concordant results with manual quality control in the
      detection of critical misalignment (sensitivity of 88% and 90% and specificity of
      93% and 95% for the tests by use of the 2 verification patients and 41 additional
      patients, respectively). CONCLUSION: QCI quantitatively represented the severity
      of misalignment. Auto-QC can help clinicians be aware of critical misalignment
      and can assist in realignment of SPECT and CT images.

PMID- 16464715
TI  - Prognostic value of cardiac I-123 metaiodobenzylguanidine imaging in patients
      with non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a
      useful tool for diagnosing cardiac autonomic neuropathy (CAN) in non-insulin
      dependent diabetes mellitus (NIDDM). However, the long-term prognostic value for
      cardiac events or mortality in NIDDM has not been clarified. METHODS AND RESULTS:
      We investigated the long-term prognostic value of cardiac MIBG imaging for both
      cardiac event and mortality owing to a variety of causes of death in NIDDM. 144
      NIDDM patients were analyzed retrospectively with the end-points of a cardiac
      event and various causes of mortality. The heart-to-mediastinum uptake ratio on
      the delayed image (H/M [d]) was obtained from anterior planar imaging. The mean
      follow-up period was 7.2+/-3.2 years. Seventeen patients had a cardiac event
      onset and 7 patients died during observation. During the same observation course,
      16 patients died, including some who died of cardiac event. Both multivariate and
      univariate analyses revealed that decreased H/M (d) (<1.7) was the independent
      predictor of long-term mortality for a variety of causes of death. Although the
      value of H/M (d) was not a significant prognostic factor for predicting a cardiac
      event, CAN, diagnosed by a combination of H/M (d) and coefficient variance of RR
      interval, was an independent predictor for the cardiac event in NIDDM.
      CONCLUSION: MIBG myocardial scintigraphy was useful for predicting cardiac events
      and long-term mortality in NIDDM.

PMID- 16464717
TI  - Operator-interactive method for simultaneous measurement of left and right
      ventricular volumes and ejection fraction by tomographic electrocardiography
      gated blood pool radionuclide ventriculography.
AB  - BACKGROUND: A method that uses single photon emission computed tomography (SPECT)
      equilibrium radionuclide angiocardiography (ERNA) to measure right ventricular
      (RV) and left ventricular (LV) volumes (in milliliters) and ejection fraction
      (EF) is described. METHODS AND RESULTS: We recorded 35 paired SPECT ERNA and
      electron beam computed tomography (EBCT) cardiac studies in 27 patients; for
      comparison with EBCT, a method for measurement of RV and LV volumes and EF with
      SPECT ERNA was developed in 18 paired studies and was validated and assessed for
      reproducibility in 17. Validation indicated that SPECT ERNA and EBCT were similar
      for measurement of RV volume (end-systolic and end-diastolic volumes in a
      combined analysis) and EF (180+/-74 mL vs 182+/-80 mL and 0.44+/-0.11 vs 0.43+/
      0.11, respectively) and for measurement of LV volume and EF (88+/-36 mL vs 84+/
      43 mL and 0.53+/-0.081 vs 0.59+/-0.07, respectively). The SPECT ERNA method was
      quite reproducible. CONCLUSIONS: RV and LV volumes and EF can be measured readily
      via SPECT ERNA.

PMID- 16464718
TI  - Usefulness of Tc-99m methoxyisobutylisonitrile scintigraphy for evaluating
      congestive heart failure.
AB  - BACKGROUND: Evidence is accumulating that technetium 99m
      methoxyisobutylisonitrile (MIBI) is not retained in the impaired myocardium. The
      purpose of this study was to determine whether the severity of congestive heart
      failure (CHF) can be evaluated by use of the washout rate (WR) of MIBI. METHODS
      AND RESULTS: Seventeen patients with CHF and ten healthy volunteers were enrolled
      in this study. MIBI and iodine 123 metaiodobenzylguanidine (MIBG) scintigraphy
      techniques were performed, and the WR was calculated. The blood was also sampled
      for the measurement of levels of brain natriuretic peptide, which is a powerful
      predictor of the severity of CHF. The WR of MIBI was higher in CHF patients
      (31.2%+/-6.3%) than in healthy volunteers (25.2%+/-4.7%) (P<.05). There were
      positive correlations between the WR of MIBI and brain natriuretic peptide levels
      (r=0.723, P<.0001) and a negative correlation between the WR of MIBI and the left
      ventricular ejection fraction (r=-0.545, P<.01). The WR of MIBI was correlated
      with that of MIBG (r=0.603, P<.01). CONCLUSIONS: MIBI scintigraphy is useful in
      evaluating the severity of congestive heart failure.

PMID- 16464719
TI  - Improvement of myocardial perfusion in coronary patients after intermittent
      hypobaric hypoxia.
AB  - BACKGROUND: Persons living at high altitude (exposed to hypoxia) have a greater
      number of coronary and peripheral branches in the heart than persons living at
      sea level. In this study we investigated the effect of intermittent hypobaric
      hypoxia on myocardial perfusion in patients with coronary heart disease. METHODS
      AND RESULTS: We studied 6 male patients (aged>or=53 years) with severe stable
      coronary heart disease. All patients were born at sea level and lived in that
      environment. They underwent 14 sessions of exposure to intermittent hypobaric
      hypoxia (equivalent to a simulated altitude of 4200 m). Myocardial perfusion was
      assessed at baseline and after treatment with hypoxia by use of exercise
      perfusion imaging with technetium 99m sestamibi. After the sessions of hypoxia,
      myocardial perfusion was significantly improved. The summed stress score for
      hypoperfusion, in arbitrary units, decreased from 9.5+ to 4.5+ after treatment
      (P=.036). There was no evidence of impairment of myocardial perfusion in any
      patient after treatment. CONCLUSIONS: Intermittent hypobaric hypoxia improved
      myocardial perfusion in patients with severe coronary heart disease. Though
      preliminary, our results suggest that exposure to intermittent hypobaric hypoxia
      could be an alternative for the management of patients with chronic coronary
      heart disease.

PMID- 16464720
TI  - The in vivo cardiac kinetics of Tc-99m N-NOET are accelerated in obese,
      hyperlipidemic Zucker rats.
AB  - BACKGROUND: Previous studies demonstrated that the intrinsic myocardial washout
      of bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium(V) (technetium 99m N
      NOET) was affected by changes occurring in the intravascular compartment such as
      variations in circulating lipid levels. We sought to determine whether the
      myocardial kinetics of Tc-99m N-NOET were affected by hyperlipidemia in a
      clinically relevant experimental model. METHODS AND RESULTS: Tc-99m N-NOET (50
      MBq/kg) and thallium 201 (12 MBq/kg) were injected intravenously into
      hyperlipidemic fa/fa Zucker rats (n=6) and their lean, normolipidemic littermates
      (n=8), and dual-isotope in vivo planar imaging was performed for 60 minutes. In
      vivo image quantification indicated significantly faster cardiac washout of Tc
      99m N-NOET in fa/fa animals versus lean animals (time constant, 411+/-64 minutes
      vs 1094+/-226 minutes, respectively; P<.05), whereas Tl-201 cardiac washout was
      not affected (356+/-85 minutes vs 337+/-53 minutes, respectively; P=not
      significant). CONCLUSION: The cardiac kinetics of Tc-99m N-NOET, but not those of
      Tl-201, were accelerated after intravenous injection of the tracer in fa/fa
      Zucker rats with circulating lipid levels similar to those encountered clinically
      in hyperlipidemic patients. The relationship between lipidemia and the rate of Tc
      99m N-NOET myocardial washout warrants further clinical investigation.

PMID- 16464721
TI  - Gated SPECT perfusion imaging for the simultaneous assessment of myocardial
      perfusion and ventricular function in the BARI 2D trial: an initial report from
      the Nuclear Core Laboratory.
AB  - BACKGROUND: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2
      Diabetes) trial, a National Heart, Lung, and Blood Institute-sponsored study in
      type 2 diabetic patients with coronary artery disease, completed patient
      recruitment in March 2005. This trial had a nuclear substudy in addition to many
      other substudies. METHODS AND RESULTS: After patient enrollment, adenosine gated
      single photon emission computed tomography perfusion imaging is performed at
      years 1 and 3. The images are interpreted at the core laboratory. Among the
      objectives of the nuclear substudy are (1) to determine the impact of the mode of
      therapy on left ventricular function, extent of ischemia, and scar; (2) to
      determine the impact of therapy on the progression/regression of ischemia/scar
      and changes in left ventricular function between years 1 and 3; and (3) to
      determine the independent and incremental prognostic value of ischemia, scar, and
      left ventricular function on the primary and secondary endpoints of the trial in
      the entire patient population and specified subgroups such as women, elderly
      patients, and minorities. CONCLUSIONS: This article describes the methodology and
      the initial experience of the nuclear core laboratory in this large multicenter
      trial and provides a summary of variables that are available for future analysis
      by the working group.

PMID- 16464722
TI  - Recent trends in coronary intravascular ultrasound: tracking atherosclerosis,
      pursuit of vulnerable plaques, and beyond.
AB  - Within the past decade, intravascular ultrasound (IVUS) has proved to be a useful
      modality for guiding coronary interventions and assessment of cardiac allograft
      vasculopathy. During the last few years, IVUS has been used increasingly for the
      evaluation of the efficacy of various possible antiatherosclerotic therapies
      including high-dose statins, antihypertensives, and recombinant apolipoprotein A
      I Milano. The recently introduced radiofrequency signal analysis is an advanced
      method for evaluation of IVUS signals to determine various histologic components
      of atherosclerotic plaques. Elastography is an allied technology for measuring
      the tissue strain that occurs in response to changes in intraluminal pressure.
      Whether radiofrequency signal analysis or elastography will become clinically
      useful tools for detecting vulnerable plaques remains an unanswered, burning
      question.

PMID- 16464724
TI  - Best patient preparation before and during radionuclide myocardial perfusion
      imaging studies.

PMID- 16464725
TI  - Atherosclerosis imaging on the molecular level.
AB  - On the basis of clinical observations that acute coronary events often result
      from rupture of atherosclerotic plaques at sites with no or minor luminal
      narrowing, the search for techniques by which to identify vulnerable, rupture
      prone lesions has developed into a quest for the holy grail of cardiovascular
      medicine. Vulnerable plaques may show characteristic morphologic features, but
      they may still differ in their biology and their activity, which ultimately leads
      to rupture. As a consequence, considerable efforts have been undertaken to
      identify biologic mechanisms of atherosclerotic lesions by use of molecular
      targeted radiolabeled probes. A variety of approaches aiming at plaque
      inflammation, apoptosis, smooth muscle cell proliferation, extracellular matrix
      activation, or platelet binding have been introduced. Nevertheless, molecular
      imaging of atherosclerosis is still a work in progress. Challenges related to the
      best targeting approach, to translation of animal model results to the clinical
      setting, to adequate imaging methodology for visualization of coronary artery
      biology, and to a suitable target patient population will need to be overcome.
      But the field is steadily moving ahead and getting closer to the ultimate goal of
      an improved clinical risk assessment through in vivo assessment of vascular
      biology.

PMID- 16464727
TI  - Multimodality imaging to diagnose takotsubo cardiomyopathy.

PMID- 16464726
TI  - Ischemia on "resting" SPECT myocardial perfusion images in a patient with
      myocardial bridging.

PMID- 16464728
TI  - Diffuse pulmonary uptake of Tc-99m sestamibi due to chemical pneumonitis.

PMID- 16464729
TI  - Letter to the editor.

PMID- 16464730
TI  - New challenges for statins:what the public can, or should, be told.

PMID- 16464731
TI  - The negative impact of litigation on women's health care.

PMID- 16464732
TI  - Host factors mediating sex differences in viral infection.

PMID- 16464733
TI  - Gender differences in pain: do emotions play a role?
AB  - BACKGROUND: Research suggests that the influence of gender on the processing and
      experience of pain is a result of several mechanisms. One mediating variable is
      emotion, which may modulate pain through an interaction of valence (pleasant
      unpleasant) and arousal (calm-excited). OBJECTIVE: This review examines whether
      gender differences in the experience and processing of emotion contribute to
      differences in the modulation and perception of pain. METHODS: An English
      language search of MEDLINE and PsycINFO was conducted from 1887 to May 2005.
      Additional literature was obtained from reference lists of articles retained in
      the initial search. RESULTS: Emotion appears to influence pain through a valence
      by-arousal interaction. Specifically, negatively valenced emotions with low to
      moderate arousal (eg, anxiety) enhance pain, whereas negatively valenced emotions
      with high arousal (eg, fear) reduce pain. In contrast, positively valenced
      emotions always reduce pain, as long as minimal arousal is achieved. Some
      evidence suggests that women are more sensitive than men to threat-related
      stimuli and thus experience more negative affect than men. This would generally
      lead to enhanced pain perception in women. It is also possible that women are
      more likely than men to experience negative affect with high arousal (intense
      fear) and thus pain inhibition. However, the relatively lower base rate of
      intense negative emotions is not likely to contribute much to gender differences
      in pain. Evidence also suggests that men may be more sensitive to positive
      events, particularly sexual/erotic stimuli, which may lead to more positive
      emotion-induced pain reduction in men, relative to women. CONCLUSIONS: This
      review suggests that gender differences in the experience of pain may arise from
      differences in the experience and processing of emotion that, in turn,
      differentially alter pain processing. Specifically, the system associated with
      negative affect may be more attuned to threatening stimuli in women, and the
      system associated with positive affect may be more attuned to pleasurable stimuli
      in men. However, there is a paucity of research directly addressing this issue;
      much of the research on this topic has failed to test a comprehensive model of
      emotion, failed to use adequate manipulation checks, or failed to use within
      subject experimental designs that control for intra- and interindividual
      differences. Therefore, it is concluded that additional research is warranted.

PMID- 16464734
TI  - Diabetic nephropathy is associated with decreased circulating estradiol levels
      and imbalance in the expression of renal estrogen receptors.
AB  - BACKGROUND: The incidence of cardiovascular and renal disease is lower in
      premenopausal women than in aged-matched men. However, in the setting of diabetes
      mellitus (DM), this "female advantage" no longer exists: the incidence and
      progression of DM and its associated end-organ complications are equal in men and
      women, regardless of age. We have recently reported that estrogen supplementation
      attenuates the progression of diabetic nephropathy, suggesting that lack of
      estrogen may nullify female sex as a protective factor against DM. OBJECTIVE:
      This study examined circulating levels of estradiol in DM and expression of
      estrogen receptor subtypes (ERa and ERP) in the nondiabetic (ND) and diabetic (D)
      kidney. METHODS: : The study was performed in ND and streptozotocin-induced D
      Sprague-Dawley rats after 2 weeks (male and female) and 12 weeks (female) of DM.
      The animals (N = 8/group) were kept either intact, ovariectomized (OVX), or OVX
      with 17beta-estradiol (E(2)) supplementation (OVX + E(2), 5 mug/kg/d). Plasma
      estradiol levels were measured by enzyme-linked immunosorbent assay, and
      expression of renal ERalpha and ERbeta was measured by immunohistochemistry and
      Western blot analysis. RESULTS: DM was associated with reduced circulating
      estradiol levels (ND: mean [SEM] 37.1 [7.2]; D: 24.5 [9.3] pg/mL; P < 0.05). The
      diabetic kidney exhibited increased expression of ERalpha protein (ND: 0.82
      [0.06]; D: 1.15 [0.09] arbitrary units; P < 0.05), but no differences in ERP were
      observed. This resulted in an overall increase in the ratio of ERalpha/ERbeta
      protein expression in the diabetic kidney. No differences in the expression of
      ERa were observed in either females or males with similar glycemic levels after 2
      weeks of DM. CONCLUSIONS: Reduced circulating levels of estradiol and imbalance
      in the expression of estrogen receptor subtypes in the diabetic kidney may
      explain why female sex is no longer a protective factor in the setting of DM.
      Thus, estradiol supplementation may be an effective regimen in attenuating the
      onset and progression of diabetic renal complications.

PMID- 16464735
TI  - Sleep, breathing, and menopause: the effect of fluctuating estrogen and
      progesterone on sleep and breathing in women.
AB  - BACKGROUND: Sleep-disordered breathing (SDB), such as obstructive sleep apnea
      (OSA), is more common in men than in women. However, menopause increases the risk
      for development of OSA. Administration of estrogen and progesterone to
      postmenopausal women with OSA decreases apnea and hypopnea during sleep.
      OBJECTIVE: Because beneficial changes can be observed soon after administration
      of a short course of hormones, we hypothesized that suppression of these hormones
      would rapidly result in the development of SDB. METHODS: Production of sex
      hormones was suppressed with daily administration of leuprolide acetate (LA), a
      gonadotropin-releasing hormone analogue, for 5 weeks in women who were
      participating in a study on pharmacologically induced menopause and physiology.
      The subjects underwent polysomnographic evaluation at baseline and after 5 weeks
      of LA administration. RESULTS: In the 12 healthy women aged 18 to 34 years who
      participated in the study, sleep architecture and respiration were normal at
      baseline. After LA administration, the subjects stopped their menses, and their
      plasma concentrations of l7beta-estradiol (preadministration, mean [SD] 33.9
      [9.0] pg/mL; post administration, 10.2 [3.4] pg/mL) and progesterone
      (preadministration, 0.48 [0.05] ng/mL; post administration, 0.40 [0.06] ng/mL)
      reached menopausal levels. Sex hormone deficiency was associated with climacteric
      vasomotor symptoms such as hot flashes and sweating. Sleep latencies and
      architecture did not change significantly with LA administration. The
      participants subjectively noticed some increased snoring that was not confirmed
      by polysomnogram. Specifically, there was no change in arousal index and no
      evidence for sleep fragmentation to suggest the presence of increased upper
      airway resistance during sleep. The apnea-hypopnea index, 0.07 (0.02) to 0.22
      (0.11) events per hour of sleep, did not change with sex hormone deficiency.
      CONCLUSIONS: In this study, sex hormone deficiency in young women resulted in
      climacteric symptoms and cessation of menses, and was not associated with sleep
      fragmentation or clinically significant SDB.

PMID- 16464736
TI  - Gender differences in diabetes mellitus and effects on self-care activity.
AB  - BACKGROUND: Effective self-care, including adherence to diet, exercise, and
      medication regimens, is an essential component of health care for individuals
      with diabetes mellitus (DM). OBJECTIVE: The goals of this study were to examine
      sex-based differences in DM and to explore the effects of gender on self-care.
      METHODS: This study was conducted retrospectively using data from the 2001
      Medical Expenditure Panel Survey (MEPS). People with DM were identified by
      International Classification of Diseases, Ninth Revision, Clinical Modification
      diagnostic code; analyses were stratified by sex. Variables included age,
      race/ethnicity, education, income, body mass index (BMI), number of
      comorbidities, physical and cognitive limitations, smoking status, and
      depression. Outcome measures were assessed by Short Form-12 (SF-12) Mental
      Component Summary (MCS) and Physical Component Summary (PCS) scores. Univariate
      analyses were determined using t, chi(2), or Fisher exact tests, as appropriate.
      Multivariate analyses examined associations between sex and SF-12 MCS/PCS scores
      adjusted for other variables. RESULTS: A total of 1653 MEPS respondents (883
      women, 770 men) with DM were identified for the current study. The women were
      significantly older than the men (61.2 vs 59.1 years), had less education (11.1
      vs 12.0 years), and had lower incomes. Women had higher calculated BMI (31.4 vs
      30.3), more comorbidities (7.8 vs 6.4), more depression, and more physical and
      cognitive limitations than did men. Women also scored lower than men on the SF-12
      MCS and PCS (47.8 vs 49.9 and 38.2 vs 41.4, respectively). All these measures
      were statistically significant (P < 0.01). In multivariate analyses, physical
      limitations, BMI, and number of comorbidities were negatively correlated, and
      income and education were positively correlated, with MCS and PCS scores.
      CONCLUSIONS: Compared with their male counterparts, diabetic women scored lower
      on measures of health status and functioning-factors that are likely to affect
      self-care activities. Sex-based differences should be considered when developing
      screening and treatment programs for people with DM.

PMID- 16464737
TI  - Prevalence of memory loss complaints and other symptoms associated with the
      menopause transition: a community survey.
AB  - BACKGROUND: Complaints of memory loss are increasingly noted as part of the
      constellation of symptoms experienced in the menopause transition. Studies
      evaluating such complaints in this population have yielded varying results.
      OBJECTIVE: The aim of this study was to determine if complaints of memory loss
      are a component of the menopause transition and a part of the menopausal symptom
      complex in a population of women not selected for menopausal symptoms. METHODS:
      Faculty members of a Long Island, New York, school district were asked to
      participate ina survey of menopausal symptoms. Demographic data were analyzed
      using chi(2) statistics. The presence or absence of memory complaints, hot
      flashes/night sweats, vaginal dryness, depression, reduced libido, and
      incontinence were analyzed as dichotomous variables in a logistic regression
      analysis after adjusting for demographic differences. RESULTS: Seventy-two
      percent (375/521) of the faculty members in the school district were eligible;of
      these, 217 (58%) completed the survey. After excluding pregnant women, those with
      hysterectomies or other nonmenopausal causes of amenorrhea, and those aged <30 or
      >60 years, 151 women were included in the analysis. Of these, 103 (68%) were
      experiencing natural menopause or perimenopause and 48 (32%) had no changes in
      menstrual cycle (the comparison group). The menopausal women were significantly
      older than the women in the comparison group (mean [SD] 51.2 [5.0] years vs 39.6
      [7.2] years; P < 0.001), and they were more likely to be white than the women in
      the comparison group (P < 0.001). Menopausal women were several-fold more likely
      to complain of memory loss (odds ratio [OR], 3.2; 95% CI, 1.2-8.8; P < 0.02), hot
      flashes/night sweats (OR, 4.3; 95% CI, 1.4-13.3; P < 0.01), and reduced libido
      (OR, 4.5; 95% CI, 1.3-15.7; P < 0.02) than were women in the comparison group,
      after adjusting for differences in age and race. There were no significant
      differences in the prevalence of depression, vaginal dryness, or incontinence.
      CONCLUSIONS: In our exploratory survey, complaints of memory loss were a part of
      the symptom complex of the menopause transition, as were hot flashes and reduced
      libido. Longitudinal followup of women with these symptoms may be helpful in
      understanding the menopause transition in women.

PMID- 16464738
TI  - Genetic variation in pro-inflammatory cytokines (interleukin-1beta, interleukin
      1alpha and interleukin-6) associated with the aggressive forms, survival, and
      relapse prediction of breast carcinoma.
AB  - OBJECTIVES: Interleukin-1 (IL-1) and interleukin-6 (IL-6) are determining factors
      in the immune and inflammatory responses to tumors cells. Experimental data
      suggest that interleukin-1 and interleukin-6 play important roles in the
      development and progression of breast cancer. We designed a broad study to
      investigate the susceptibility and prognostic implications of the genetic
      variation in IL-1alpha, IL-1beta and IL-6 in breast carcinoma. EXPERIMENTAL
      DESIGN: We used the polymerase chain reaction and restriction enzyme digestion to
      characterize the genetic variation of IL-1alpha, IL-1beta and IL-6 in 305,
      unrelated Tunisian patients with breast carcinoma and 200 healthy control
      subjects. Associations between the genetic markers and the clinicopathological
      parameters, the specific overall survival rate (OVS) of breast carcinoma and the
      disease free-survival rate (DFS) were assessed using univariate and multivariate
      analyses. RESULTS: Both IL-6 (-597) GA and IL-6 (-174) GC heterozygous genotypes
      were found to be significantly associated with breast carcinoma (OR = 1.59, p =
      0.024 and OR = 1.61, p = 0.022 respectively). A highly significant association
      was found between the (+3954) T allele of IL1-B gene and the aggressive phenotype
      of breast carcinoma as defined by the high histological grade, axillary lymph
      node metastasis and large tumor size. The IL-1alpha (-889) TT homozygous genotype
      showed a significant association with reduced disease-free survival and/or
      overall survival rate. The IL-1beta (+3954) TT, IL-6 (-597) GG and IL-6 (-174) GG
      homozygous genotypes were found to be associated with reduced DFS but not with
      overall survival. CONCLUSIONS: The polymorphisms in the promoter region of the IL
      6 gene may represent a marker for the increased risk of breast carcinoma. Genetic
      variations in IL-1alpha, IL-1beta and IL-6 may predict the clinical outcome of
      breast carcinoma.

PMID- 16464739
TI  - Differential response of interleukin-2 production to chronic copper
      supplementation in healthy humans.
AB  - BACKGROUND: Copper (Cu) is an essential trace element for many biological
      processes including maintenance of both innate and acquired branches of immunity.
      OBJECTIVE: To measure the effect of copper supplementation on IL-2 and TNF-alpha
      production in subjects with lower and higher ceuloplasmin (Cp) values within
      normal range. DESIGN: Healthy adults (17 men and 16 women) with normal-low (low
      Cp) and normal-high Cp (high Cp) values were supplemented with 10 mg Cu/day (as
      CuSO(4)) during 2 months. METHOD: Before and after supplementation blood
      mononuclear cells were incubated in the absence or presence of
      phytohaemagglutinin or lipopolysaccharide for induction of IL-2 and TNF-alpha,
      respectively. The secretion of cytokines was measured by ELISA. Cu
      supplementation did not modify classical biochemical markers of Cu status.
      RESULTS: After supplementation, a significant increase in IL-2 production was
      found only in subjects with normal-low plasma Cp. Before and after Cu
      supplementation geometric mean and range +/- 1 SEM values were 1,566 (1,287
      1,905) and 2,514 (2,159-2,927) pg/mL, respectively (two-way ANOVA for repeated
      measures: Cp level p < 0.001; time = NS; interaction Cp level and time p < 0.05).
      We did not observe changes in TNF-alpha production after Cu supplementation.
      CONCLUSIONS: Cu supplementation increased secretion of IL-2 and not TNF-alpha,
      which suggests an activation of proliferative but not inflammatory cytokines.
      These results support hypothesis that IL-2 may be a good indicator to identify a
      subgroup of individuals (polymorphism) who differs in Cu metabolism.

PMID- 16464740
TI  - Differential effects of tumor necrosis factor-alpha and CD40L on NF-kappa B
      inhibitory proteins I kappa B alpha, beta and epsilon and on the induction of the
      Jun amino-terminal kinase pathway in Ramos Burkitt lymphoma cells.
AB  - Interaction between the CD40 ligand and its cognate receptor is known to affect
      various aspects of B-cell biology. Less is known about the biological
      consequences of B-cell signaling through tumor necrosis factor alpha (TNF-alpha)
      and its two receptors. We have used Ramos germinal center (GC)-derived Burkitt's
      lymphoma (BL) cells as a model system to compare some of the early signaling
      events of TNF-alpha and CD40L on the NF-kappaB and c-Jun amino-terminal kinase
      (JNK) pathways. We have previously found that both TNF-alpha and CD40L induced
      enhanced cell aggregation, adherence and modified cell surface morphology of
      Ramos cells. In the present report, it was found that treatment with either TNF
      alpha or CD40L resulted in a rapid degradation (within 15 min) of IkappaBalpha,
      followed by a recovery period lasting up to a few hours. The level of
      IkappaBbeta, another inhibitory molecule of the NF-kappaB pathway, also decreased
      following treatment with CD40L or TNF-alpha. However, whereas CD40L induced a
      rapid drop without significant recovery within 2 h, TNF-alpha caused a slow and
      gradual decline of IkappaBbeta. In addition, treatment with CD40L resulted in a
      gradual and modest decline of up to 60% of the level of IkappaBepsilon within 2
      h, whereas a much smaller decline was seen with TNF-alpha (approx. 20%) Our
      results thus show that in Ramos cells, TNF-alpha and CD40L have common, as well
      as differential, signaling effects on the IkappaBalpha, IkappaBbeta and
      IkappaBepsilon, which form inhibitory complex(es) with the NF-kappaB cytosolic
      proteins. We also found that CD40L, but not TNF-alpha activates the JNK pathway
      through transient phosphorylation of its threonine183/tyrosine185 residues. As
      expected, c-Jun, which is known to be a substrate of JNK, was also phosphorylated
      at serine residue 73 by treatment with CD40L, but not by TNF-alpha.

PMID- 16464741
TI  - Association between interleukin-6 polymorphism and age-at-onset of type 1
      diabetes. Epistatic influences of the tumor necrosis factor-alpha and interleukin
      1beta polymorphisms.
AB  - Multiple immune mediators have been mentioned as playing a role in the
      pathomechanism of type1 DM. Interleukin (IL)-1beta, and tumor necrosis factor
      (TNF)-alpha play a central role in the autoimmune destruction of pancreatic beta
      cells, whereas IL-6 inhibits TNF-alpha secretion, and may have some protecting
      effects. In our study, we aimed to investigate the association between these
      three cytokines' single nucleotide polymorphisms (IL-6 gene G(-174)C, TNF-alpha
      gene G(-308)A and IL-1beta gene C(3954)T polymorphisms) and age-at-onset of type
      1 diabetes mellitus (T1DM) in 165 diabetic children (median age: 17 years).
      Polymorphisms were determined using the PCR-RFLP method. We found that the age-at
      onset of T1DM was significantly different in patients with a different IL-6
      genotype (median age-at-onset of T1DM was: 8, 6 and 4.5 years in children with
      the (-174)GG, GC and CC genotypes, respectively; p < 0.01). Adjusted for TNF
      alpha and IL-1beta polymorphisms, patients with a IL-6 (-174)CC genotype have a
      3.0-fold (95% CI: 1.2-7.1) increased risk of developing diabetes before the age
      of 6 years than (-174)G allele carrier patients. However, we found this
      association to be present only in patients who carried the TNF-alpha (-308)A or
      IL-1beta (3954)T allele, i.e. in patients with high TNF-alpha and high IL-1beta
      producer genotypes. We suppose that in the case of high TNF-alpha and IL-1beta
      producer genotypes, elevated proinflammatory cytokine levels result in a higher
      production of IL-6 in (-174)G allele carrier patients. This elevated IL-6 level
      may have a protective effect against the development of T1DM and may delay the
      destruction of pancreatic beta-cells.

PMID- 16464742
TI  - Intracellular T-cell cytokine levels are age-dependent in healthy children and
      adults.
AB  - Intracellular detection of cytokines via fluorescent antibody staining and flow
      cytometry has quickly become a standard method in experimental immunology.
      However, in pediatrics most studies have been hampered by the exclusion of
      healthy control individuals or have been skewed by neglecting to observe age
      dependent differences in cytokine production. We therefore intended to establish
      normal values for different age groups and to describe the age-dependent
      development of cytokine profiles. Whole blood from 46 healthy children and 33
      adults was analyzed by flow cytometry after stimulation with PMA, ionomycin and
      Mmonensin, and staining with anti-cytokine and surface antibodies. In the
      pediatric population, we found a significant positive correlation between age and
      intracellular cytokine levels of IFN-gamma, IL-2, IL-4 and TNF-alpha in CD4+
      cells, as well as for IFN-gamma and TNF-alpha in CD8+ cells. In adulthood, no
      such striking trend could be detected, but significant correlation was found for
      IL-10 in CD4+ cells and IFN-gamma in CD8+ cells as well as for TNF-alpha in both
      cell subgroups. We present here the first systematic analysis of intracellular
      cytokine production in normal, healthy children between the ages of 0 to 18 years
      compared to results in adults. These data may provide a reference basis for the
      study of cytokine secretion patterns, and they also demonstrate a significant
      maturation of the T-cell cytokine production capacity from birth to adulthood.

PMID- 16464743
TI  - Interleukin-32, CCL2, PF4F1 and GFD10 are the only cytokine/chemokine genes
      differentially expressed by in vitro cultured rheumatoid and osteoarthritis
      fibroblast-like synoviocytes.
AB  - Since cytokines and chemokines are important actors in rheumatoid arthritis (RA),
      the aim of this study was to compare the gene expression profiles in cultured
      fibroblast-like synoviocytes (FLS) obtained from patients with either RA, or
      osteoarthritis (OA), focusing our analysis on genes for cytokines and chemokines,
      and their respective receptors. Gene expression in cultured FLS (third passage)
      from eight patients with RA (RA-FLS) were compared with gene expression in
      cultured FLS from nine patients with OA (OA-FLS) using Affymetrix Human Genome
      U133 Plus 2.0 Array microarray, allowing analysis of over 54,000 transcripts.
      Among the 171 genes studied (241 probes), limiting the selection of
      differentially expressed genes to a significant value (p < 0.05), and a
      differential ratio of expression > 1.6, only four genes, namely IL-32, CCL2,
      PF4F1 and GDF10 were found to be differentially expressed. Out of these four
      genes, only higher expression of CCL2 has been reported previously in RA. The
      newly described cytokine IL-32 was the most prominently differentially expressed
      gene in the present study, with higher expression in RA-FLS than in OA-FLS (p <
      0.0073). IL-32 might have a previously unidentified pivotal role in RA.

PMID- 16464744
TI  - Anti-retroviral therapy in HIV-infected patients: in vitro effects of AZT and
      saquinavir on the response of CD4 and CD8 lymphocytes to interleukin-7.
AB  - IL-7 is a crucial cytokine regulating lymphopoiesis and peripheral T lymphocyte
      homeostasis. Plasma IL-7 levels increase during HIV infection and, although
      antiretroviral therapy (ARV therapy) decreases these levels, they fail to return
      to normal. Immune reconstitution in most ARV-treated patients is only partial. We
      tested the possibility that the IL-7R system might be affected by ARV drugs. The
      effects of the antireverse transcriptase AZT and the anti-protease saquinavir on
      CD3- and CD3+CD28-induced T lymphocyte stimulation, in the presence (or absence)
      of IL-7, were studied in vitro. Small amounts of the drugs did not interfere with
      the capacity of IL-7 to stimulate T cell proliferation, but higher concentrations
      significantly decreased IL-7-induced T cell proliferation both in cells from HIV
      infected patients and in cells from healthy donors. IL-7 is known to down
      modulate its own receptor on the surface of CD4 and CD8 T lymphocytes in vitro.
      In CD4 lymphocytes from healthy donors or HIV-infected patients, neither AZT, nor
      saquinavir, nor a combination of the two, interfered with this property. In
      contrast, AZT + saquinavir worsened the IL-7-induced down-regulation of CD127
      expression by CD8 T cells from HIV-infected patients, while no such effect was
      observed with CD8 T cells from healthy donors. Our data suggest that, under
      certain conditions, antiretroviral therapy could interfere with the expression
      and function of the IL-7/IL-7R system, and more particularly it may affect the
      CD8-lymphocyte compartment of HIV-infected patients.

PMID- 16464745
TI  - Disruption of T cell regulatory pathways is necessary for immunotherapeutic cure
      of T cell acute lymphoblastic leukemia in mice.
AB  - Acute lymphoblastic leukemia (ALL) is the most common cancer in children. In
      recent years, the outcome has been globally improved by current therapies, but it
      remains poor in patients with high, persistent residual disease following the
      first course of chemotherapy, prompting evaluation of the possible beneficial
      effects of immunotherapy protocols. In this study, we hypothesized that the
      disruption of two immunoregulatory pathways controlling the auto-reactive T cell
      response might synergize with dendritic cell-based immunotherapy of the disease,
      which is considered to be poorly immunogenic. In this study, we used TAL1xLMO1
      leukemia cells adoptively transferred in mice, to generate murine leukemia with
      poorly immunogenic cells as a model for human T-ALL. Subsequently, these animals
      were treated with several different immunotherapeutic protocols. We compared the
      efficiency of a classical, dendritic cell-based immunotherapy (injection of
      dendritic cells loaded with tumor-derived antigenic products), to a combined
      treatment associating injection of antigen-loaded dendritic cells and disruption
      of the two immunoregulatory pathways: CD25+ suppressive T cells and cytotoxic T
      lymphocyte-associated antigens (CTLA-4). We show that this combined treatment
      resulted in cure, concomitantly with in vivo generation of immune memory, and TNF
      alpha secretion. This study demonstrates that the disruption of these two
      immunoregulatory pathways synergized with immunostimulation by dendritic cells
      loaded with tumor-derived antigens, and paves the way for the testing of this
      combination in clinical trials.

PMID- 16464746
TI  - Keratinocytes as targets for interleukin-10-related cytokines: a putative role in
      the pathogenesis of psoriasis.
AB  - Cytokines are key factors in the cross talk between the immune system and other
      systems including hepatic, nervous, cardiac and cutaneous systems, leading to an
      adaptive and integrated response of the organism to stress. They are also
      involved in the regulation of many processes, including hematopoiesis, the immune
      response and inflammation. IL-10 is one of the most important anti-inflammatory
      cytokines. Five cytokines structurally related to IL-10 have been described and
      presently form this family of cytokines: IL-19, IL-20, IL-22, IL-24 and IL-26. In
      contrast to IL-10, these cytokines display pro-inflammatory activities in
      different tissues, including skin. Indeed, some of them induce an inflammatory
      keratinocyte gene expression profile and an epidermis histology resembling
      psoriatic lesions. In this review, we discuss recent knowledge about the effects
      of cytokines of the IL-10 family on keratinocytes and their potential role in
      psoriasis, a cutaneous inflammatory disease.

PMID- 16464747
TI  - Disturbance of iron metabolism in Parkinson's disease -- ultrasonography as a
      biomarker.
AB  - A central role of iron in the pathogenesis of Parkinson's disease (PD) has been
      discussed for many years. So far, however, a biomarker indicating increased iron
      levels in the substantia nigra (SN) in PD patients has been missing. Performing
      transcranial ultrasound we detected an increased area of SN echogenicity as a
      typical echofeature in PD, visible already in the early stages of the disease and
      in subjects with subclinical impairment of the nigrostriatal system. Animal
      studies and post mortem analyses of human brain tissue revealed that this
      echofeature is associated with increased iron levels of the substantia nigra as
      well as a reduced neuromelanin content. The apparently autosomal dominant
      inheritance of this echofeature in relatives of patients with idiopathic PD
      indicates a primary role of disturbances of iron metabolism in PD. Consequently
      performed mutation analyses in genes involved in brain iron metabolism lead to
      the discovery of specific mutations in the ferritin-H, IRP2 and HFE gene in
      single PD patients. Moreover, variations in the ceruloplasmin gene were found to
      be associated with PD or SN hyperechogenicity. Functional relevance of some of
      these mutations for iron metabolism could be proven. Therefore, SN
      hyperechogenicity can be regarded as biomarker for both: impairment of the
      nigrostriatal system and increased iron levels of the SN. Future studies aim at
      substantiating the hypothesis that healthy subjects with SN hyperechogenicity
      indeed represent a population at risk for nigrostriatal degeneration, which would
      have a significant impact on therapeutical options.

PMID- 16464749
TI  - Lipid peroxidative damage on malathion exposure in rats.
AB  - Lipid peroxidation is one of the major outcomes of free radical-mediated injury
      to tissue in vivo, including the central nervous system (CNS). The aim of this
      study was to examine whether malathion, a commonly used organophosphorus (OP),
      might induce oxidative stress in cerebrospinal fluid, blood serum and brain
      structures in male Wistar rats. Malathion was administered intraperitoneally in
      the doses of 25, 50, 100 and 150 mg/kg for 28 days. Oxidative damage was
      determined by measuring the thiobarbituric acid reactive species (TBARS) content,
      as an index of lipid peroxidation. TBARS concentration in the cerebrospinal fluid
      (CSF) and brain structures were increased, but a decrease in TBARS concentration
      in serum was observed. The results of the present study suggest the usefulness of
      TBARS measurement as a good biomarker in the estimation of malathion-induced
      oxidative stress affecting CSF and brain structures.

PMID- 16464748
TI  - Rotenone produces opposite effects upon mouse striatal dopamine function as a
      result of environmental temperature.
AB  - Rotenone is a commonly used pesticide that can function as an environmental
      neurotoxin. Rotenone is a known mitochondrial complex I inhibitor which can lead
      to oxidative stress and results in dopaminergic cell death. Another environmental
      factor known to exacerbate oxidative stress and result in striatal dopaminergic
      cell death is elevated environmental temperature. In this study we evaluated the
      effects of a single injection of various doses of rotenone (0.65, 1.3 and 2.6
      mg/kg) on striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC)
      concentrations in CD-1 mice and compared this with a single injection of two
      doses of methamphetamine (MA - 10 or 20 mg/kg), a known striatal DA depleting
      agent, as administered to mice maintained at 21 degrees C (Experiment 1). These
      results were then compared to striatal DA and DOPAC concentrations of mice
      treated with rotenone (1.3 or 2.6 mg/kg) or MA (10 or 20 mg/kg) administered to
      mice maintained at 28 degrees C (Experiment 2). A single injection of rotenone to
      mice maintained at 21 degrees C resulted in a significant increase in DA and
      decrease in DOPAC concentrations for all doses tested compared to controls,
      whereas a single injection of MA at the same temperature resulted in a
      significant decrease in DA and no change in DOPAC concentrations. At a
      temperature of 28 degrees C, a single injection of rotenone resulted in a
      significant decrease in both DA and DOPAC concentrations similar to that seen
      with the MA-treated mice. Collectively, these results indicate that rotenone
      interacts with environmental temperature to produce opposite effects upon
      striatal DA concentrations -- significantly increasing striatal DA when
      administered at 21 degrees C and significantly decreasing striatal DA when
      administered at 28 degrees C, while producing similar decreases in striatal DOPAC
      under both temperatures.

PMID- 16464750
TI  - Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB
      activation by inhibiting the proteasome function.
AB  - Curcumin, a natural polyphenolic compound, has long been known as an anti-tumour
      and anti-inflammatory compound; although, the common mechanism through which it
      exhibits such properties are remains unclear. Recently, we reported that the
      curcumin-induced apoptosis is mediated through the impairment of ubiquitin
      proteasome system (UPS). Here, we show that curcumin disrupts UPS function by
      directly inhibiting the enzyme activity of the proteasome's 20S core catalytic
      component. Like other proteasome inhibitors, curcumin exposure induces neurite
      outgrowth and the stress response, as evident from the induction of various
      cytosolic and endoplasmic reticulum chaperones as well as induction of
      transcription factor CHOP/GADD153. The direct inhibition of proteasome activity
      also causes an increase in half-life of IkappaB-alpha that ultimately leads to
      the down-regulation of NF-kappaB activation. These results suggest that curcumin
      induced proteasomal malfunction might be linked with both anti-proliferative and
      anti-inflammatory activities.

PMID- 16464751
TI  - The influence of antidotal treatment of low-level tabun exposure on cognitive
      functions in rats using a water maze.
AB  - In this study, the influence of antidotal treatment of tabun poisoning on
      cognitive function, in the case of low-level tabun exposure, was studied. The
      impairment of cognitive function was evaluated by the measurement of spatial
      learning and memory in rats poisoned with a sublethal dose of tabun and treated
      with atropine alone or in combination with newly developed oximes {K027 [1-(4
      hydroxyiminomethyl- pyridinium)-3-(4-carbamoylpyridinium) propane dibromide] and
      K048 [1-(4-hydroxyimino- methylpyridinium)-3-(4-carbamoylpyridinium) butane
      dibromide]} or currently available oxime (trimedoxime), using the Morris water
      maze. While atropine alone caused an impairment of studied cognitive functions,
      the addition of an oxime to atropine contributes to the improvement of cognitive
      performance of treated tabun-poisoned rats regardless of the type of oxime. The
      differences in the ameliorative effects of oximes on atropine-induced mnemonic
      deficits were not significant. Therefore, each low-level nerve agent exposure
      should be treated by complex antidotal treatment consisting of anticholinergic
      drug and oxime.

PMID- 16464753
TI  - The influence of oxime and anticholinergic drug selection on the potency of
      antidotal treatment to counteract acute toxic effects of tabun in mice.
AB  - The influence of newly developed oximes, K027 [1-(4-hydroxyiminomethylpyridinium)
      3-(4-carbamoylpyridinium) propane dibromide] and K048 [1-(4
      hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) butane dibromide], or
      currently used oximes (pralidoxime, obidoxime, trimedoxime, HI-6) and
      anticholinergic drugs (atropine, benactyzine) on the ability of antidotal
      treatment to eliminate tabun-induced acute toxic effects was studied in mice. The
      therapeutical efficacy of trimedoxime and both newly developed oximes (K027,
      K048) is significantly higher than the potency of pralidoxime (regardless of the
      choice of anticholinergic drug), obidoxime (in the case of its combination with
      atropine) and the oxime HI-6 (in the case of its combination with benactyzine).
      All studied oximes with the exception of pralidoxime and the oxime HI-6, when
      combined with benactyzine, appear to be more efficacious in the elimination of
      toxic effects of the lethal dose of tabun than their combination with atropine.
      The findings support the hypothesis that the choice of acetylcholinesterase
      reactivators as well as the anticholinergic drug selection are important for the
      effectiveness of an antidotal mixture in the case of antidotal treatment of tabun
      induced acute poisonings.

PMID- 16464752
TI  - Methylene blue prevents neurodegeneration caused by rotenone in the retina.
AB  - An experimental optic neuropathy model was used to test the hypothesis that
      methylene blue may protect the retinal ganglion cell layer from neurodegeneration
      caused by rotenone. Rotenone is a widely used pesticide that inhibits complex I,
      the first enzyme of the mitochondrial respiratory chain. Complex I dysfunction is
      linked to the degeneration of retinal ganglion cells in Leber's optic neuropathy.
      Methylene blue is a reduction-oxidation agent that can act as a powerful
      antioxidant and also as an enhancer of the electron transport chain, preventing
      formation of mitochondrial oxygen free radicals and promoting oxygen consumption.
      The neurodegeneration of the retina was studied in mice with intravitreal
      microinjection of rotenone alone, or in combination with increasing doses of
      methylene blue, in one eye, and the vehicle in the contralateral control eye. The
      effect of rotenone and rotenone plus methylene blue was investigated using two
      histological stains, complex I and Nissl, and two measurements, morphometric
      layer thickness and non-biased stereological cell counts. Rotenone induced
      neurodegeneration in the retinal ganglion cell layer 24 h after injection, as
      indicated by significant reductions in both the thickness and cell numbers of the
      retinal ganglion cell layer of eyes microinjected with rotenone as compared to
      the control eyes. This neurodegeneration was prevented in a dose dependent manner
      by the injection of methylene blue along with rotenone. It was concluded that
      rotenone-induced degeneration in the ganglion cell layer can be prevented by
      intravitreal injection of methylene blue. In vitro experiments showed that
      methylene blue is both a powerful antioxidant as well as an enhancer of cellular
      oxygen consumption and is able to reverse the oxidative stress and decrease in
      oxygen consumption induced by rotenone in brain homogenates. The findings suggest
      that methylene blue may be a promising neuroprotective agent in optic neuropathy
      and perhaps other neurodegenerative diseases caused by mitochondrial dysfunction.

PMID- 16464754
TI  - Successful treatment of rhinocerebral zygomycosis with a combination of
      caspofungin and liposomal amphotericin B.
AB  - Genera of the order Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia,
      Apophysomyces, Cunninghamella, and Saksenaea) cause an angioinvasive infection
      called zygomycosis. Mortality rates can approach 100% depending on the patient's
      underlying disease and form of zygomycosis. We report here on the unusual case of
      a patient with acute myelogenous leukemia and zygomycosis unresponsive to
      monotherapy with liposomal amphotericin B, who responded favorably following the
      addition of the echinocandin caspofungin acetate.

PMID- 16464755
TI  - Improvement in the symptoms of smooth muscle dystonia during eculizumab therapy
      in paroxysmal nocturnal hemoglobinuria.
AB  - Aberrant smooth muscle dystonia during hemolytic episodes in paroxysmal nocturnal
      hemoglobinuria (PNH) is implicated in the symptoms of abdominal pain, dysphagia
      and erectile dysfunction. Here we report two PNH patients treated with the
      complement inhibitor, eculizumab. Complement inhibition has been sustained for
      over 2 years and results in resolution of intravascular hemolysis and
      amelioration of symptoms associated with smooth muscle contractions.

PMID- 16464756
TI  - Parvovirus B19 co-infection with falciparum malaria: a cause of severe anemia.

PMID- 16464757
TI  - Bulbar palsy in multiple myeloma.

PMID- 16464758
TI  - Bortezomib-induced Sweet's syndrome.
AB  - Sweet's syndrome is an uncommon acute skin disease, associated with a variety of
      medical problems. The drug-induced variant is even rarer. We describe two cases
      of this syndrome associated with the administration of the proteasome inhibitor
      bortezomib. The diagnostic criteria for drug-induced Sweet's syndrome as proposed
      by Walker and Cohen were fulfilled. Vasculitis and neutrophilic eccrine
      hidradenitis were excluded.

PMID- 16464759
TI  - Skin lesions induced by bortezomib.
AB  - We report on six cases of skin lesions induced by bortezomib in patients treated
      for relapsed multiple myeloma. The folliculitis-like rash appeared in the second
      cycle of bortezomib therapy. Therapy with prednisone led to rapid resolution of
      the skin lesions. Prednisone 10 mg before each infusion of bortezomib was
      necessary to prevent recurrence of the rash while antihistamines alone were
      ineffective.

PMID- 16464760
TI  - Two newborns with nutritional vitamin B12 deficiency: challenges in newborn
      screening for vitamin B12 deficiency.
AB  - Vitamin B12 deficiency causes decreased Methionine Synthase and L-Methylmalonyl
      CoA Mutase activity and results in accumulation of Homocysteine, Methylmalonic
      acid and Propionylcarnitine. Propionylcarnitine is included in tandem mass
      spectrometry-based newborn screening programs for detection of certain inborn
      errors of metabolism. We report two asymptomatic newborns with Vitamin B12
      deficiency due to maternal deficiencies. One was detected incidentally at 3 weeks
      of age; the second on supplemental newborn screening based on elevated
      Propionylcarnitine at 2 days of age. This illustrates the potential for false
      negative results for Vitamin B12 deficiency screening by acylcarnitine profiling
      in newborn screening. Homocysteine and Methylmalonic acid may be better markers
      of Vitamin B12 deficiency. In conclusion, we suggest measuring Methylmalonic
      acid, Propionylcarnitine and Homocysteine levels in blood spots in expanded
      newborn screening in order to detect asymptomatic newborns with Vitamin B12
      deficiency. Further studies are needed to establish the sensitivity of these
      three markers in screening for Vitamin B12 deficiency.

PMID- 16464761
TI  - Hodgkin's disease.

PMID- 16464762
TI  - Abnormal positron emission tomography (PET) scan secondary to the use of
      hematopoietic growth factors.

PMID- 16464763
TI  - Ophthalmic zoster sine herpete presenting as oculomotor palsy after marrow
      transplantation for acute myeloid leukemia.

PMID- 16464764
TI  - Lymphoid neoplasms in Bulgaria according to the WHO classification (2001). The
      experience of the National Center of Haematology.
AB  - The aim of the present study was to assess the incidence of lymphoma subtypes in
      the largest cohort of patients in Bulgaria, referred to the National Center of
      Haematology and Transfusiology between 01.01.2003 and 31.12.2004, applying the
      WHO classification criteria, including precursor and mature cell neoplasias,
      plasmacytoma and Hodgkin lymphomas. A total of 790 cases were newly diagnosed.
      Hodgkin lymphomas comprised 24.6% of the cases, B-cell neoplasias - 66.5% whereas
      T/NK-cell neoplasias - 6.9% of the total. Specimens were inadequate for
      subclassification in 2.2% of the cases. Detailed data on the subtypes are
      presented and compared to reported data from other geographic locations.

PMID- 16464765
TI  - High D-dimer level at presentation in patients with venous thrombosis is a marker
      for malignancy.

PMID- 16464766
TI  - Getting back to the fundamentals of clinical ethics.

PMID- 16464767
TI  - Clinical bioethics in china: the challenge of entering a market economy.
AB  - Over the last quarter-century, China has experienced dramatic changes associated
      with its development of a market economy. The character of clinical practice is
      also profoundly influenced by the ways in which reimbursement scales are
      established in public hospitals. The market distortions that lead to the over
      prescription of drugs and the medically unindicated use of more expensive drugs
      and more costly high-technology diagnostic and therapeutic interventions create
      the most significant threat to patients. The payment of red packets represents a
      black-market attempt to circumvent the non-market constraint on physicians' fees
      for services. These economic and practice pattern changes are taking place as
      China and many Pacific Rim societies are reconsidering the moral foundations of
      their professional ethics and their bioethics. The integrity of the medical
      profession and the trust of patients in physicians can only be restored and
      protected if the distorting forces of contemporary public policy are altered.

PMID- 16464769
TI  - Advance directives and the severely demented.
AB  - Should advance directives (ADs) such as living wills be employed to direct the
      care of the severely demented? In considering this question, I focus primarily on
      the claims of Rebecca Dresser who objects in principle to the use of ADs in this
      context. Dresser has persuasively argued that ADs are both theoretically
      incoherent and ethically dangerous. She proceeds to advocate a Best Interest
      Standard as the best way for deciding when and how the demented ought to be
      treated. I put forth a compromise position: both ADs and the Best Interest
      Standard have roles to play in guiding the care of the severely demented.

PMID- 16464768
TI  - "Nobody understands": on a cardinal phenomenon of palliative care.
AB  - In the clinical practice of palliative medicine, recommended communication models
      fail to approximate the truth of suffering associated with an impending death. I
      provide evidence from patients' stories and empiric research alike to support
      this observation. Rather than attributing this deficiency to inadequate training
      or communication skills, I examine the epistemological premises of the biomedical
      language governing the patient-physician communication. I demonstrate that the
      contemporary biomedicine faces a fundamental aporetic occlusion in attempting to
      examine death. This review asserts that the occlusion defines, rather than simply
      complicating, palliative care. Given the defining place of aporia in the care for
      the dying, I suggest that this finding shape the clinicians' responses to the
      needs of patients in clinical care and in designing palliative research. Lastly,
      I briefly signal that a genuinely apophatic voice construing the occlusion as a
      mystery rather than an aporia may be superior to the present communication and
      empathy models.

PMID- 16464770
TI  - The ethics and science of placebo-controlled trials: assay sensitivity and the
      Duhem-Quine thesis.
AB  - The principle of clinical equipoise requires that, aside from certain exceptional
      cases, second generation treatments ought to be tested against standard therapy.
      In violation of this principle, placebo-controlled trials (PCTs) continue to be
      used extensively in the development and licensure of second-generation
      treatments. This practice is typically justified by appeal to methodological
      arguments that purport to demonstrate that active-controlled trials (ACTs) are
      methodologically flawed. Foremost among these arguments is the so called assay
      sensitivity argument. In this paper, I take a closer look at this argument.
      Following Duhem, I argue that all trials, placebo-controlled or not, rely on
      external information for their meaningful interpretation. Pending non-circular
      empirical evidence that we can trust the findings of PCTs to a greater degree
      than the findings of ACTs, I conclude that the assay sensitivity argument fails
      to demonstrate that placebo-controlled trials are preferable, methodologically or
      otherwise, to active-controlled trials. Contrary to the intentions of its
      authors, the fundamental lesson taught by the assay sensitivity argument is
      Duhemian: the validity of all clinical trials depends on external information.

PMID- 16464771
TI  - Identity, harm, and the ethics of reproductive technology.
AB  - The controversial question of whether a future child can be harmed by the use of
      reproductive technology turns on the way that the future child's identity is
      understood. As a result, analysis of the ethical and legal obligations to the
      children of reproductive technology that are based upon the possibility of such
      harm depends upon the conception of identity that is used. This paper reviews the
      contributions of two recent books, David DeGrazia's Human Identity and Bioethics
      (2005) and Philip Peters' How Safe is Safe Enough? (2004) to this area of
      inquiry. It suggests that the use of a narrative rather than numerical conception
      of identity makes it possible to coherently claim that future children can be
      harmed by the use of reproductive technologies and that, as a result, potential
      parents can have obligations regarding the use of those technologies based upon
      that possibility of harm.

PMID- 16464772
TI  - Modelling the spread of HIV/AIDS in China: the role of sexual transmission.
AB  - The study presented here is an exploration of the implications of patterns of
      sexual behaviour for the spread of HIV in China, using a bio-behavioural
      macrosimulation model. To reflect the uncertainty surrounding key parameters,
      analyses of varied scenarios are used to show a range of possible outcomes
      consistent with variations in selected biological and behavioural inputs. The
      latter are estimated from a nationwide survey of sexual behaviour recently
      conducted in China, a country with an emerging HIV/AIDS epidemic, where it is
      feared that HIV/AIDS will spread to the general population via heterosexual
      transmission. The results highlight the primacy of the levels and distribution of
      sexual activity in the population. They offer some guidelines for understanding
      and interpreting the potential implications of current and prospective changes in
      sexual behaviour for the spread of HIV/AIDS in the world's largest population,
      and also highlight the need to collect better data on sexual behaviour for the
      estimation of key model inputs.

PMID- 16464773
TI  - Religious differentials in marital fertility in The Hague (Netherlands) 1860
      1909.
AB  - Previous studies of the marital fertility transition in Europe have found
      religious differentials. Using data collected from the population registers of
      The Hague, our aim in this study is to search for answers to the following
      questions: whether religious differentials result from socio-economic
      characteristics; to what extent religious ideology explains the behaviour of
      religious groups; which proximate determinants account for the religious
      differentials; and whether the Jews were forerunners in the marital fertility
      transition in Europe. The results provide some evidence of relatively low levels
      of parity-dependent fertility control among Jews before the transition and among
      Catholics during the transition. Religious ideology probably accounts for the low
      level of fertility control among Catholics. The ultimate reason for the
      relatively high marital fertility among Jews before the transition remains
      unclear. Our findings do not support the hypothesis that Jews were forerunners in
      the marital fertility transition.

PMID- 16464774
TI  - Trends in old-age functioning and disability in Japan, 1993-2002.
AB  - Disability is a burden to individuals and society. Population ageing, combined
      with the fact that disability is most common among the elderly, has focused
      attention on trends in old-age disability. This study estimates trends in
      functioning and disability among Japanese elderly from 1993 to 2002 and contrasts
      the patterns with those found in the USA. Japan is an especially interesting
      country because its age structure is relatively old, and it currently has the
      highest life expectancy in the world despite the fact that just 50 years ago its
      life expectancy was in the bottom half of all countries. As in the USA,
      disability rates have fallen. If it were not for the gains in disability between
      1993 and 2002, there would have been 1.1 million more disabled elderly in 2002.
      The reductions were experienced broadly across socio-demographic and economic
      groups. Increases in education across cohorts are associated with the declines in
      disability.

PMID- 16464776
TI  - A model with long-term survivors for the analysis of current-status nuptiality
      data.
AB  - The model proposed in this paper combines a logistic regression model and a
      Weibull regression model for the analysis of current-status data. This joint
      model allows a simultaneous estimation of two sets of effects on the covariates:
      one on the probability that the event occurs (also known as quantum) and the
      other on the timing of the event. Thus, the model can be seen either as an
      extension of a survival-analysis model for use with current-status data where a
      survival fraction is added in order explicitly to take into account the
      possibility that the event may never occur, or as an extension of survival
      analysis with long-term survivors to the analysis of current-status data. As an
      illustrative application we apply our model to a study of nuptiality in
      seventeenth-century Italy.

PMID- 16464775
TI  - The effect of number of births on women's mortality: systematic review of the
      evidence for women who have completed their childbearing.
AB  - Mortality in women who have completed their childbearing may increase with the
      number of births experienced because of maternal depletion or a trade-off between
      reproduction and mortality. We report a systematic review of the evidence on this
      association. We searched Medline, Embase, Popline, and the Science Citation Index
      for published and unpublished studies up to September 2003, and the book
      catalogues of relevant London libraries. Where necessary we also contacted
      authors for additional information. Mortality declined with increasing numbers of
      births in twelve historical cohorts, but in eight contemporary cohorts the
      highest mortality was seen in the nulliparous and in women with more than four
      births. All effects seen were small and there were few statistically significant
      results. Studies examining the relationship in other ways (such as by linear
      trends or by mean number of births by age at death) found inconsistent
      associations. We discuss methodological, social, and biological factors that may
      have affected these associations.

PMID- 16464777
TI  - Reliability of reasons for early termination of breastfeeding: application of a
      bivariate probability model with sample selection to data from surveys in
      Malaysia in 1976-77 and 1988-89.
AB  - Although extensively collected, data on people's reasons for their behaviour
      provided retrospectively have been met with some scepticism on the grounds that
      they may be subject to biases and errors that jeopardize their usefulness. This
      study investigates, for a sample of 1,327 births, the reliability with which
      women in Peninsular Malaysia recalled, at intervals 12 years apart, reasons for
      not initiating or for stopping breastfeeding less than 3 months after a birth.
      Overall, we find low to moderate reliability of recall. Levels of reliability are
      relatively high for some reasons (the child died and no or insufficient milk) but
      low for some others (child ill, breastfeeding inconvenient). Results from
      selection models show that reliability does not vary with the length of time
      since the child's birth but is inversely related to socio-economic status
      (proxied by education and employment). Social status, social norms, and health
      related factors appear to be significant influences on women's consistency of
      reporting.

PMID- 16464778
TI  - Differentials in the femininity ratio among centenarians: variations between
      northern and southern Italy from 1870.
AB  - Significant differentials have been observed between Italian regions in the
      distribution of centenarians by sex, from two women per man in the south to over
      eight in certain regions in the north. In order to explain these differentials we
      studied the evolution of the femininity ratio (FR), using a longitudinal approach
      to follow the ageing process in two cohorts, and making use of nearly all the
      statistical data available since the time of the Unification of Italy in 1870.
      Significant differentials in the FR observed at the age of 100 are mainly due to
      mortality differentials among men over the age of 60. The high mortality of men
      in the north and their low mortality in the south are the main explanations of
      why the FRs are higher in the north and lower in the south. Mortality
      differentials among women have only a marginal impact.

PMID- 16464780
TI  - Haemoglobin A1c reference method.

PMID- 16464781
TI  - The many faces of proinsulin.

PMID- 16464782
TI  - Serum matrix metalloproteinase-9 and venous bypass graft occlusion.
AB  - OBJECTIVE: The primary results after coronary artery bypass grafting are good,
      but early clinical events as a result of graft occlusion are still a problem.
      Early occlusions are thought to be due to thrombosis or fibrointimal hyperplasia
      superimposed by thrombosis, but the etiology of these phenomena is not fully
      understood. Matrix metalloproteinase-9 has been suggested to have a role in graft
      occlusion ex vivo. MATERIAL AND METHODS: We investigated whether the level of
      serum matrix metalloproteinase-9 reflects its proposed role in occlusion of vein
      grafts. The study population consisted of 30 men with a history of myocardial
      infarction and 31 men without myocardial infarction who had undergone coronary
      artery bypass grafting. All the men were asymptomatic. RESULTS: Among the
      patients with no previous myocardial infarction, serum matrix metalloproteinase-9
      level was significantly higher in those with graft occlusion than in those
      without occlusion (54.0+/-11.0 microg/L and 41.7+/-10.4 microg/L, respectively, p
      = 0.006), and it correlated positively with the number of occluded grafts (R =
      0.55, p = 0.001). In the patients with myocardial infarction, this effect was not
      detected. CONCLUSIONS: Serum matrix metalloproteinase-9 reflected the occurrence
      of vein graft occlusion in subjects with no previous history of myocardial
      infarction.

PMID- 16464783
TI  - Saliva collection using cotton buds with wooden sticks: a note of caution.
AB  - The aims of the present study were to investigate whether the cotton-tipped
      applicators (cotton buds) used to collect saliva in infants can be stored un
      centrifuged prior to cortisol analysis, and to test whether there is any
      difference in results between wooden and plastic-shafted sticks. Saliva was
      collected from 10 healthy adults using 6 cotton buds, i.e. 3 with wooden sticks
      and 3 with plastic sticks. The samples were then centrifuged at three different
      time-points: immediately after collection, after 24 h and after 48 h. Using
      cotton buds with wooden sticks, median salivary cortisol was significantly lower
      after 24 h (40 %) (p<0.001) and after 48 h (49 %) (p<0.001) of storage than it
      was of the samples centrifuged immediately. There was no significant difference
      between the samples centrifuged immediately and those centrifuged after 24 h and
      48 h when saliva was collected using the cotton buds with plastic sticks. It is
      concluded that cotton buds with wooden sticks should not be used in studies of
      salivary cortisol unless it is possible to centrifuge the saliva immediately.
      Moreover, it is inadvisable to alternate between cotton buds with wooden and
      plastic sticks in the same study when collecting saliva for analysis of cortisol.

PMID- 16464784
TI  - Reliability of bioelectrical impedance methods in detecting body fluids in
      elderly patients with congestive heart failure.
AB  - OBJECTIVE: To investigate the reliability of bioelectrical impedance analysis
      (BIA) in estimating total body water (TBW) and extracellular water (ECW) in
      elderly patients suffering from congestive heart failure (CHF). MATERIAL AND
      METHODS: In 72 elderly subjects, 34 with CHF (aged 83.9+/-6.9 years) and 38
      healthy controls (78.7+/-7.5 years), TBW and ECW values were assessed using
      dilution methods, and bioelectrical variables were measured using single
      frequency BIA (SF-BIA) at 1 and 50 kHz, and bioelectrical spectroscopy (BIS).
      RESULTS: In CHF patients, Ht(2)/R(1) correlated weakly with TBW (r = 0.56) and
      ECW (0.47). In both healthy controls and CHF patients, TBW correlated strongly
      with Ht(2)/R(50), Ht(2)/R(0), Ht(2)/R(8) and Ht(2)/Zc. Using multiple regression
      analysis and the Bland-Altmann approach, SF-BIA at 50 kHz and BIS proved similar
      in predicting TBW for both the explained variance (R(2)~0.89) and the limits of
      agreement. In all subjects, ECW was estimated best by including height, weight
      and Ht(2)/R(0 )(R(2) 0.75) or Ht(2)/Zc (R(2) 0.77) in multivariate models, while
      SF-BIA at 50 kHz did not explain more than 71 % of ECW variability. The SEE % was
      nonetheless about twice the SEE % for estimating TBW. CONCLUSIONS: SF-BIA at 1
      kHz is unreliable in predicting body fluids in elderly people with CHF. SF-BIA at
      50 kHz and BIS are useful for estimating TBW in healthy elderly people and in
      cases of water imbalance, but both methods are less reliable in estimating ECW,
      particularly in conditions of fluid overload.

PMID- 16464785
TI  - Inosine monophosphate dehydrogenase activity in renal allograft recipients during
      mycophenolate treatment.
AB  - OBJECTIVE: Mycophenolic acid (MPA) exerts its immunosuppression by inhibiting
      inosine 5'-monophosphate dehydrogenase (IMPDH), depleting activated lymphocytes
      of guanine nucleotides and retarding their proliferation. An optimal strategy for
      monitoring has not been established for mycophenolate mofetil (MMF) in renal
      transplantation, and clinical investigations of the pharmacokinetic
      pharmacodynamic relationship are warranted. MATERIAL AND METHODS: Mycophenolic
      acid pharmacokinetics and whole blood cell IMPDH activity were investigated in
      two separate groups of renal allograft recipients. One group was studied within
      the 12-h dose interval, while the second group was examined by pre-dose samples
      pre-transplant and then repeatedly during 8 weeks post-transplant. RESULTS: An
      inverse relationship between plasma MPA and IMPDH activity within the dose
      interval was demonstrated. Minimum IMPDH activity was a median 8 % of values pre
      MMF dose, coinciding with the MPA peak. Six hours post-dose, IMPDH activity had
      returned to pre-dose values. Patients receiving MMF had a 4.5-fold higher pre
      dose enzyme activity than transplanted patients without MMF. During the 8 weeks
      post-transplant, the median MPA trough concentration was fairly stable. Following
      an initial decrease during the first 4 days post-transplant, IMPDH activity
      gradually increased during the 40 days post-transplant, reaching 5-fold the pre
      transplant values. CONCLUSIONS: Provided that the changes in IMPDH activity in
      whole blood cells predict the clinical effect, these pharmacokinetic
      pharmacodynamic findings may prove useful in the attempts to identify optimal
      timing and range for the monitoring of mycophenolate in renal transplantation.
      The question of whether MPA concentrations or measurements of IMPDH activity per
      se will be the optimal way of monitoring this immunosuppressant remains open and
      will only be answered by prospective clinical testing.

PMID- 16464786
TI  - Increased levels of C-reactive protein and interleukin-6 in hyperhomocysteinemic
      subjects.
AB  - OBJECTIVE: Elevated plasma homocysteine concentration is considered to be an
      independent risk factor for cardiovascular disease. However, the mechanisms by
      which hyperhomocysteinemia are related to vascular disease are unclear. High
      sensitivity C-reactive protein (CRP), a marker of inflammation, has been reported
      to be an independent predictor of future myocardial infarction among clinically
      healthy individuals. Interleukin (IL)-6 is a regulator of CRP and has a key role
      in initiation of inflammation. The aim of this study was to investigate whether
      individuals with increased plasma homocysteine concentrations have altered levels
      of serum CRP and IL-6. MATERIAL AND METHODS: Serum concentrations of CRP and IL-6
      were measured in 39 individuals with hyperhomocysteinemia and in 39 control
      subjects matched for gender, age and body mass index (BMI). In addition, the
      inflammatory effect of IL-6 on peripheral blood mononuclear cells was measured.
      RESULTS: Compared to controls, hyperhomocysteinemic subjects have elevated serum
      levels of CRP and IL-6 (p < or =0.001 and p < 0.005, respectively). Importantly,
      this raised level of IL-6 was also seen in hyperhomocysteinemic individuals
      without accompanying hypercholesterolemia or cardiovascular disease. IL-6
      increased the release of monocyte chemoattractant protein-1 from peripheral blood
      mononuclear cells, with particularly enhancing effects in cells from patients
      with hyperhomocysteinemia. CONCLUSIONS: These data suggest that enhanced
      inflammation may be associated with homocysteine-related cardiovascular disease,
      possibly involving IL-6-related mechanisms.

PMID- 16464787
TI  - Increased urinary aquaporin-2 excretion in response to furosemide in patients
      with chronic heart failure.
AB  - OBJECTIVE: Patients with chronic heart failure (CHF) have decreased ability to
      excrete water and increased urinary excretion of aquaporin-2 (U-AQP2). The
      natriuretic and diuretic effects of furosemide are antagonized by an increased
      reabsorption of sodium and water in the collecting ducts. It is unknown whether
      aquaporin-2 (AQP2) renal water channels are involved in this compensatory
      reabsorption. We tested the hypothesis that U-AQP2 increases after a single
      intravenous dose of furosemide in CHF patients. MATERIAL AND METHODS: In a
      randomized, single-blind, placebo-controlled, crossover study, we measured the
      effect of furosemide (80 mg) on U-AQP2, urine volume, free water clearance
      (C(H2O)) and fractional excretion of sodium (FE(Na)) in 12 CHF patients. Plasma
      concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II),
      aldosterone (Aldo), atrial (ANP) and brain natriuretic peptides (BNP) were
      measured during the study. U-AQP2 and hormones were determined by
      radioimmunoassays. RESULTS: Furosemide increased U-AQP2 (140 %), urine volume
      (280 %), C(H2O) (95 %) and FE(Na) by a factor of 15 (p<0.008 for all), and also
      AVP (51 %), PRC, Ang II (86 %) and Aldo (59 %) (p<0.021 for all). ANP and BNP did
      not change. CONCLUSIONS: In CHF, furosemide increased the vasopressin level,
      which stimulated water reabsorption via the APQ2 water channels. This is most
      likely a compensatory phenomenon in addition to the increase in the renin
      angiotensin system to prevent excess loss of sodium and water. However, both
      these effects were overridden by the effect of furosemide, as shown by increased
      free water clearance and sodium excretion.

PMID- 16464788
TI  - Children with acute lymphoblastic leukaemia have high plasma levels of total
      homocysteine at time of diagnosis.
AB  - OBJECTIVE: Cancer can induce venous thromboembolic complications for various
      reasons. As part of a greater study, acquired and congenital prothrombotic risk
      factors were investigated in children with leukaemia or non-Hodgkin's lymphoma
      and compared with similar investigations in children with congenital heart
      defects. MATERIAL AND METHODS: Blood samples were taken from 60 children with
      newly diagnosed leukaemia or lymphoma and 133 children with congenital heart
      defects in the course of a scheduled cardiac catheterization. When children with
      cancer were in remission, analyses of acquired prothrombotic risk factors were
      repeated. Children with cancer were observed for symptoms of thromboembolism
      throughout their treatment period. RESULTS: Total homocysteine levels were
      significantly raised in children with cancer (median value 10.0 micromol/L) as
      compared with the levels in children with congenital heart diseases (5.0
      micromol/L) (p<0.001), while children with acute lymphoblastic leukaemia had the
      highest values. The median level of lipoprotein(a) was slightly increased in
      children with newly diagnosed leukaemia or lymphoma (105 mg/L versus 100 mg/L,
      p<0.001), and levels of coagulation inhibitors were higher (p<0.001). Total
      homocysteine levels normalized when children attained remission of cancer
      disease. Two children had symptoms of acute thrombosis. CONCLUSIONS: Raised
      concentrations of total homocysteine were frequent in children with newly
      diagnosed cancer, but this normalized when the children were in remission. The
      clinical significance of our observations and the impact on venous
      thromboembolism have yet to be defined.

PMID- 16464790
TI  - Clinical relevance of pulmonary toxicity in adjuvant breast cancer irradiation.

PMID- 16464791
TI  - Radiological pulmonary findings after breast cancer irradiation: A prospective
      study.
AB  - The aim of this study was to evaluate radiation-induced pulmonary abnormalities
      of breast cancer patients. Altogether 202 consecutive patients receiving
      postoperative radiotherapy entered the study. Plain chest radiographs taken at
      entry and 3, 6 and 12 months after radiotherapy were evaluated according to
      modified Arriagada classification. In addition, pulmonary symptoms were recorded.
      Supplementary high-resolution computed tomography (HRCT) was employed in a
      subgroup of patients (n?=?15). Plain radiographs were interpreted by a
      radiologist, and uncertain findings were re-evaluated by a radiologist together
      with a radiation oncologist. Grade 2 pneumonitis was the most common abnormality.
      The proportion of patients yielding a grade 2 finding was 22.5%, 28.1%, and 16.0%
      at three, six, and twelve months, respectively. There were 2 normal findings in
      HRCTscans, and 8 in plain radiographs of the same patients. Radiological lung
      abnormalities are common after radiotherapy, but they are usually reversible, and
      their significance for the patient's well-being is minor. No correlation between
      symptoms and lung or pleural reactions was seen.

PMID- 16464792
TI  - Gastrin-releasing-peptide in neuroendorine tumours.
AB  - In a substantial proportion of cases with endocrine malignant disease the primary
      lesion cannot be localised and the pathologist hesitates upon the origin of the
      tumour. Well differentiated neuroendocrine carcinomas of the small bowel can
      usually be identified by the strong serotonin immunoreactivity, but foregut
      carcinoids may also stain positive for serotonin and the differential diagnosis
      between the various foregut tumours may be difficult. We examined if
      immunostaining for gastrin-releasing-peptide (GRP) may aid in establishing the
      origin of an unknown neuroendocrine tumour. Tumour tissue from 79 patients (27
      lung carcinoids, 4 thymic carcinoids, 4 gastric neuroendocrine tumours, 17
      pancreatic well differentiated neuroendocrine carcinomas, 1 duodenal well
      differentiated neuroendocrine tumour and 26 well differentiated neuroendocrine
      carcinomas of the small bowel) were immunostained with antibodies against GRP and
      serotonin. Positive staining for GRP was found in 12/27 lung carcinoids. All
      other tumour types were consistently GRP-negative (p?<?0.0001). We conclude that
      immunostaining for GRP may aid in defining the origin of the tumour, and that GRP
      immunoreactivity increases the suspicion of a lung carcinoid.

PMID- 16464793
TI  - A cross sectional quality of life study of 116 recurrence free head and neck
      cancer patients. The first use of EORTC H&N35 in Danish.
AB  - The quality of life questionnaire EORTC C30 with the head and neck specific
      module H&N35 has been validated in many languages and cultural settings, but the
      H&N35 module has not been formally translated to and validated in Danish. This
      validation was the purpose of the current study. In a cross sectional study 116
      of 120 (97%) recurrence free head and neck cancer patients returned a valid
      questionnaire. The patients were attending follow up after radical radiotherapy
      (n=83), surgery (n=33) for cancer of the larynx (n=44), pharynx (n=34) or oral
      cavity (n=38). The previously described psychometric properties of the
      questionnaire were confirmed with the Danish translation. Nevertheless, there
      were some foreseeable problems with heavily skewed endpoints. Several scales of
      the questionnaire were sensitive to patient, tumour and treatment related
      factors: Good performance, high age, male gender, laryngeal cancer, low tumour
      stage and surgery correlated with a low score on the symptom scales or high score
      on the function scales. Symptom intensity increased with time since therapy in
      patients who had surgery and decreased in the irradiated patients. In conclusion,
      the current validation study confirmed the psychometric properties of the EORTC
      H&N35 questionnaire. The questionnaire detected correlations between clinical
      factors (performance status, gender, age, stage, site, time since therapy,
      treatment) and a large number of QoL factors. EORTC H&N35 in conjunction with
      EORTC C30 is a valid and informative tool in assessing quality of life, also in
      Danish head and neck cancer patients.

PMID- 16464794
TI  - Management of high-grade bone sarcomas over two decades: the Norwegian Radium
      Hospital experience.
AB  - All cases of high-grade osteosarcoma (OS) (n = 196) and Ewing's sarcoma of bone
      (ES) (n = 56) treated at the Norwegian Radium Hospital in the period 1980-1999
      were analyzed retrospectively. They were allocated to consecutive ten-year
      periods by their time of diagnosis. Patient and tumour characteristics have been
      relatively stable. Eighty percent of all patients received surgical treatment and
      the amputation rate decreased from 64% to 23%. The percentage of patients
      receiving chemotherapy has remained around 80%. The use of radiotherapy in
      primary treatment decreased gradually from 33% to 18%. Sarcoma specific survival
      (SSS) at five years for all patients increased significantly from 39% to 53%.
      Similar trends for improvement were seen for both OS and ES. In multivariate
      analysis, independent prognostic factors for improved SSS were non-metastatic
      disease at diagnosis, age under 40, extremity tumours, small tumours and
      treatment from 1995 onwards. No major new treatment options have emerged over
      these 20 years. The improved outcome appears partly to be due to refinements in
      the use of existing modalities and improved quality and integration of
      multidisciplinary approaches. Improved formalized organisation of the sarcoma
      group and annual audited reports of its patient and research activity may also
      have contributed to improved focus and performance.

PMID- 16464795
TI  - Can reproductive pattern explain better survival of women with lung cancer?
AB  - We examined whether women's survival from lung cancer is influenced by hormonal
      factors associated with reproductive events. In all 4235 women and 4797 men born
      on 1 January 1935 or later with lung cancer diagnosed in 1978-1999 were
      identified in the Danish Cancer Registry and followed up to 31 December 2002 by
      linkage to the Central Population Registry. Cox regression analysis was used to
      estimate hazard rate ratios (HRs), and survival probabilities were calculated.
      Both nulliparous women and men without children had worse prognoses than those
      with children (women: HR 1.14; CI 1.03-1.26; men: HR 1.24; CI 1.15-1.34). The 5
      year survival rate of nulliparous women with adenocarcinoma was 20.3%, while that
      for parous women was 20.5%; the corresponding rates for men were 13.0% and 16.6%.
      The number of children affected the risk for death in both sexes, indicating that
      the finding is not due to hormonal factors but to unmeasured elements such as
      socio-economic status or lifestyle factors related to parenthood.

PMID- 16464796
TI  - Expression of sex steroid receptor subtypes in normal and malignant breast tissue
      - a pilot study in postmenopausal women.
AB  - Female sex steroids are implied in breast cancer development. The estrogen (ER)
      and progesterone (PR) receptor subtypes may have different roles to modulate the
      cellular response. Paired samples of cancer and adjacent normal tissue were
      collected from postmenopausal women at surgery for ductal breast cancer. The
      expression of ERa, ERss, PRA and PRB was quantified by immunostaining and
      digitized image analysis. We found ERss to be significantly reduced in breast
      cancer tissue (35% vs 50%; p?=?0.001) and there was also a decrease of the
      ERss/ERa ratio. Among women using hormones at the time of diagnosis tumor tissue
      showed higher values for both PRB and PRA, as compared to women without such
      treatment. The results extend previous animal data to be valid also in women.
      There is evidence that loss of ERss expression may relate to estrogen dependent
      tumor progression. Increased PR expression could possibly relate to breast cancer
      risk during combined estrogen/progestogen treatment.

PMID- 16464797
TI  - Mismatch repair, p53 and chromosomal aberrations in primary colorectal
      carcinomas.
AB  - Colorectal carcinoma progresses via at least two genetic pathways. Microsatellite
      instability, due to defective mismatch repair genes, characterizes one pathway
      and gross chromosomal instability another. The involvement of p53 and mismatch
      repair gene abnormalities within these pathways has not been fully explored. We
      aimed to investigate the relationships of p53 and mismatch repair gene defects on
      gross chromosomal aberrations detected by comparative genomic hybridization in 49
      colorectal carcinomas. Tumours demonstrating loss of expression for hMLH1 or
      hMSH2 proteins demonstrated a highly significant attenuation in the number of
      gross chromosomal aberrations (p = 0.007) and were less likely to show p53
      overexpression (p = 0.02). Within the mismatch repair normal tumours, p53 status
      did not affect the total number of chromosomal aberrations but p53 overexpression
      was significantly associated with a higher frequency of amplifications at 8q22
      ter and at 13q21-22. Colorectal cancer demonstrates distinct molecular phenotypes
      and should be sub-classified accordingly.

PMID- 16464798
TI  - Benefits and risks of palliative capecitabine based therapy to elderly patients
      with advanced colorectal cancer: Danish single centre experiences.
AB  - This study aimed to compare efficacy and toxicity of palliative chemotherapy for
      elderly and younger colorectal cancer patients. Patients aged 24-69 (n = 203) and
      70-82 years (n = 57) with advanced colorectal cancer were consequetively treated
      with first line capecitabine monotherapy or combined with oxaliplatin (XELOX).
      The response rates were 37% and 33% (P = 0.61), the median times to progression
      were 5.5 and 6.0 months (P = 0.84, hazard ratio (HR) 1.09; 95% confidence
      interval: 0.71-1.68), and median overall survival times were 8.4 and 12.5 months
      (P = 0.07, HR 1.48; 1.04-2.38) for elderly and younger patients, respectively.
      Elderly patients had similar frequencies of Common Toxicity Criteria (CTC) grade
      3 or 4 toxicity (P > 0.05) and number of treatment courses (P = 0.44), and
      maintained performance status as well as younger patients (P = 0.68). Palliative
      capecitabine based therapy for advanced colorectal cancer should be considered
      also for elderly who are in good performance without major comorbidities.

PMID- 16464799
TI  - Percutaneous laser ablation in patients with isolated unresectable liver
      metastases from colorectal cancer: Results of a phase II study.
AB  - We prospectively evaluated the safety, local tumor control, and impact on
      survival parameters of percutaneous laser ablation (PLA) in patients with
      colorectal liver metastases not amenable to surgical resection. The study
      included 44 individuals with 75 unresectable liver metastases and no known
      extrahepatic disease. The median number of metastases treated for each patient
      was one, with a range of 1-4. Metastases had a median diameter of 3.4 cm (range
      0.5-9 cm), and a median volume of 16.8 cm(3) (range 0.4-176.4 cm(3)). All
      patients also received systemic chemotherapy with modalities that differed
      according to the type of response to PLA. After treatment, 61% (46/75) of the
      tumors were ablated completely. The likelihood of achieving a complete ablation
      was significantly higher when metastases had a diameter <3.0 cm (p = 0.004).
      Overall survival was 30.0+/-12.7 months in patients with a complete ablation, and
      20.2+/-10.2 months in those with a partial ablation (p = 0.002). There were no
      major complications during or after PLA, the most frequent side effect being
      abdominal pain that required analgesics. These findings indicate that PLA can be
      safely used as an adjunct to chemotherapy in unresectable colorectal liver
      metastases, and may have a positive impact on survival.

PMID- 16464800
TI  - The burden of scientific progress: growing inequalities in the delivery of cancer
      care.
AB  - Novel targeted therapies are now a reality in oncology. The monoclonal antibodies
      trastuzumab, rituximab, cetuximab and bevacizumab have a proven benefit in both
      advanced and early stage cancers. Furthermore impressive new technologies such as
      gene profiling, circulating tumour cells and proteomics are becoming major tools
      for prognostic assessment and prediction of response to certain treatments.
      Whilst this is certainly good news for patients it comes at a price, many of
      these technologies are very expensive and may result in unprecedented
      inequalities in the delivery of cancer care. The largest impact may be on
      developing countries, but inequalities are starting to be felt in some developed
      nations. Strategies to tackle the resource implications need to be addressed
      alongside the development of these technologies.

PMID- 16464801
TI  - Radiation-induced spinal glioblastoma multiforme.

PMID- 16464802
TI  - Metastatic granular cell tumor: a case report and review of the literature.

PMID- 16464803
TI  - Hepatocellular carcinoma--Pathological complete response to oral capecitabine,
      megestrol and thalidomide.

PMID- 16464804
TI  - Response of pseudomyxoma peritonei to gemcitabine.

PMID- 16464805
TI  - Mutational analysis of P-loop domains of proapoptotic Nod1 and ARTS genes in
      colon carcinomas.

PMID- 16464807
TI  - News from the Nordic colleges of general practitioners. Developments in Finnish
      general practice.

PMID- 16464806
TI  - Experiences with the use of oxaliplatin in esophageal carcinoma.

PMID- 16464809
TI  - Effectiveness of strategies to implement brief alcohol intervention in primary
      healthcare. A systematic review.
AB  - OBJECTIVE: To review systematically the available literature on implementation of
      brief alcohol interventions in primary healthcare in order to determine the
      effectiveness of the implementation efforts by the health are providers. KEY
      QUESTION: To what extent have the efforts to implement brief alcohol
      interventions in primary healthcare environments been successful? METHOD:
      Literature search from Medline, Cinahl, PsychLIT, Cochrane. SETTING: Primary
      healthcare. MATERIAL: A total of 11 studies encompassing 921 GPs, 266 nurses, 88
      medical students, and 44 "non-physicians" from Europe, the USA, and Australia.
      MAIN OUTCOME MEASURES: Material utilization, screening, and brief intervention
      rates. ANSWER: Intervention effectiveness (material utilization, screening, and
      brief intervention rates) generally increased with the intensity of the
      intervention effort, i.e. the amount of training and/or support provided.
      Nevertheless, the overall effectiveness was rather modest. However, the studies
      examined were too heterogeneous, not scientifically rigorous enough, and applied
      too brief follow-up times to provide conclusive answers.

PMID- 16464811
TI  - Coping with headache.
AB  - OBJECTIVE: To describe self-initiated actions and cognitive strategies used for
      coping by women who suffer from episodic tension-type headache. DESIGN:
      Qualitative data from focus-group interviews were analysed according to Giorgi's
      phenomenological approach, inspired by Lazarus's theory of coping. SUBJECTS: A
      total of 15 women with tension-type headache, 20-60 years old, were recruited to
      three different focus groups through newspaper advertising. RESULTS: To cope with
      episodic tension-type headache, rhythm and balance in actions like eating,
      drinking, and sleeping were essential. Several women used thermal modulation.
      Exercise was important. Taking charge of their own time, pace, and level of
      commitment and accepting the fact that they had to live with their headache were
      cognitive strategies used. IMPLICATIONS: The general practitioner should identify
      the woman's choice of actions and cognitive strategies to manage her headache,
      and support her coping skills.

PMID- 16464810
TI  - Intensive community pharmacy intervention had little impact on triptan
      consumption: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the impact of an intensive pharmaceutical care campaign
      targeting inappropriate use of triptans. DESIGN: Randomized controlled trial.
      SETTING: 22 community pharmacies in the County of Funen, Denmark. SUBJECTS: A
      total of 1123 triptan users at intervention pharmacies and 1340 at control
      pharmacies. INTERVENTION: Intervention pharmacy staff received information on
      migraine and other types of headache, detection of inappropriate triptan use and
      other drug-related problems, and techniques for establishing a dialogue with
      patients. Intervention consisted of a folder and a structured dialogue with the
      pharmacy staff. The folder included questions aimed at detecting overuse and
      inappropriate triptan use. MAIN OUTCOME MEASURES: Change in average triptan
      consumption in doses per month measured by means of a prescription database with
      information on all purchases of reimbursed drugs at the level of the individual
      patient. RESULTS: Overall, intervention had no statistically significant short
      term impact on patients' consumption of triptans either among incident users
      (intervention/control ratio 1.02; 95% confidence interval 0.95 to 1.12), or among
      prevalent users (1.02; 0.97 to 1.08). No effects were observed after 6 and 9
      months, apart from a possible borderline effect after 9 months among prevalent
      users with intermediate triptan consumption (0.93; 0.87 to 1.00). CONCLUSION: The
      pharmaceutical care campaign did not reduce the use of triptans.

PMID- 16464812
TI  - General practitioners' attitudes toward reporting and learning from adverse
      events: results from a survey.
AB  - OBJECTIVE: To investigate GPs' attitudes to and willingness to report and learn
      from adverse events and to study how a reporting system should function. DESIGN:
      Survey. SETTING: General practice in Denmark. MAIN OUTCOME MEASURES: GPs'
      attitudes to exchange of experience with colleagues and others, and circumstances
      under which such exchange is accepted. SUBJECTS: A structured questionnaire sent
      to 1198 GPs of whom 61% responded. RESULTS. GPs had a positive attitude towards
      discussing adverse events in the clinic with colleagues and staff and in their
      continuing medical education groups. The GPs had a positive attitude to reporting
      adverse events to a database if the system granted legal and administrative
      immunity to reporters. The majority preferred a reporting system located at a
      research institute. CONCLUSION: GPs have a very positive attitude towards
      discussing and reporting adverse events. This project encourages further research
      and pilot projects testing concrete reporting systems.

PMID- 16464813
TI  - Women at risk of coronary heart disease experience barriers to diagnosis and
      treatment: a qualitative interview study.
AB  - OBJECTIVE: To explore barriers in the health service to diagnosis and treatment
      experienced by women at increased risk of coronary heart disease (CHD). DESIGN:
      Qualitative study using semi-structured interviews. SETTING: Norway. SUBJECTS:
      Twenty women diagnosed with heterozygous familial hypercholesterolemia (FH)
      recruited through a lipid clinic. RESULTS: Women reported three specific barriers
      related to diagnosis and treatment of CHD. They had to struggle to take a
      cholesterol test; they experienced that their risk was being downplayed by
      doctors; and that their symptoms of CHD were misinterpreted when they consulted
      doctors for evaluation and treatment. CONCLUSION: Stereotyping CHD as a man's
      disease may result in barriers to diagnosis and treatment for women. Doctors
      should ask the patient about the family history of CHD if a concern about heart
      disease is on the patient's agenda.

PMID- 16464814
TI  - Infection prevention at day-care centres: feasibility and possible effects of
      intervention.
AB  - OBJECTIVE: To study the effect of an educationally oriented intervention
      programme, with the recommendations from the National Board of Health and Welfare
      as a base. DESIGN: A prospective intervention study. SETTING: Six day-care
      centres in Vaxjo, Sweden. Three centres comprised the intervention group and
      three constituted the control group. SUBJECTS AND MAIN OUTCOME MEASURES: The
      parents and personnel completed a questionnaire on their views concerning
      information about infectious diseases. During a nine-month period, parents of all
      children reported every episode of absence, the number of days absent, the cause
      of absence, and any contact with doctors or prescription of antibiotics. RESULTS:
      The guidelines were implementable in routine child day-care. Parents found
      regular information valuable and felt better informed about infectious diseases.
      Multilevel analyses showed no statistically significant results of the
      intervention. "Infection-prone" children had more sickness absence, doctor's
      consultations, and antibiotic prescriptions than those not "infection-prone".
      CONCLUSION: It is possible to implement an educationally oriented intervention
      programme directed against infectious diseases in child day-care. No significant
      effect of the intervention was found, which is why a larger intervention study is
      needed.

PMID- 16464815
TI  - Age and gender effect on the use of herbal medicine products and food supplements
      among the elderly.
AB  - OBJECTIVE: To describe the users of herbal medicine products and food supplements
      with regard to age and gender specifically among persons aged > or = 60 years.
      DESIGN: A descriptive study with baseline data from a longitudinal study of the
      elderly, stratified into different age cohorts (60-69, 70-79, 80-89, and > or =
      90 years). SETTING: Blekinge county, situated in south-eastern Sweden. SUBJECTS:
      In total 1380 persons aged 60-96 years (median age 78 years). MAIN OUTCOME
      MEASURES: Current use of herbal medicine products and the use of food
      supplements. RESULTS: Of the participants, 264/1380 (19.1%) used at least one
      herbal medicine product, 184/1380 (13.3%) used at least one food supplement and
      382/1380 (27.7%) used herbal medicine products and/or food supplements. In all
      regression models, women had a higher probability of using herbal medicine and/or
      food supplements in comparison with men. Focusing on the use of herbal medicine
      products alone and the combination of using herbal medicine and/or food
      supplements, decreased use was seen with increasing age. However, 27.9% were
      still users of herbal medicine products and/or food supplements in the age group
      80-89 years. In comparison, 14% were users in the age group > or = 90 years. Age
      did not have an impact on the probability of taking food supplements. CONCLUSION:
      General practitioners need to consider the high use of herbal medicine products
      and food supplements among the elderly when making decisions on treatment.

PMID- 16464816
TI  - Urinary incontinence in the elderly: attitudes and experiences of general
      practitioners. A focus group study.
AB  - OBJECTIVE: To assess general practitioners' (GPs') attitudes to urinary
      incontinence in elderly patients and their experiences in the application of the
      Dutch College of General Practitioners' guideline in daily practice. DESIGN: Two
      existed groups of six GPs working in villages and seven GPs working in urban
      practices. METHOD: Two focus-group discussions with recording of discussions and
      transcription. Transcripts were analysed by two independent researchers. RESULTS:
      During the discussions three main themes of attitudes came forward: (1)
      therapeutic nihilism of GPs and low motivation of patients, (2): GPs experienced
      lack of time because of difficulties in explaining the therapy and because of
      impaired mobility of older patients, (3) because of the complexity of the problem
      and co-morbidity, GPs as well as patients were reluctant to treat the UI. The
      most remarkable findings in the application of the guideline were: (1) because of
      the barriers mentioned above, physical examination did not take place in spite of
      GPs' conviction as to the benefit of it; (2) GPs' knowledge of treatment options
      in the elderly with UI is substandard. CONCLUSION: Several patient (comorbidity,
      impaired mobility, low motivation, and acceptance of the problem) and GP factors
      (therapeutic nihilism, lack of time and knowledge) interfere with good management
      of UI in the elderly.

PMID- 16464817
TI  - Biological exposure indicators: quantification of biological variability using
      toxicokinetic modeling.
AB  - Compartmental and physiologically based toxicokinetic modeling coupled with Monte
      Carlo simulation were used to quantify the impact of biological variability
      (physiological, biochemical, and anatomic parameters) on the values of a series
      of bio-indicators of metal and organic industrial chemical exposures. A
      variability extent index and the main parameters affecting biological indicators
      were identified. Results show a large diversity in interindividual variability
      for the different categories of biological indicators examined. Measurement of
      the unchanged substance in blood, alveolar air, or urine is much less variable
      than the measurement of metabolites, both in blood and urine. In most cases, the
      alveolar flow and cardiac output were identified as the prime parameters
      determining biological variability, thus suggesting the importance of workload
      intensity on absorbed dose for inhaled chemicals.

PMID- 16464818
TI  - Silica exposure on construction sites: results of an exposure monitoring data
      compilation project.
AB  - To expand on the limited size and scope of construction silica exposure studies,
      a silica monitoring data compilation project was initiated through the American
      Conference of Governmental Industrial Hygienists Construction Committee. Personal
      silica exposure monitoring data was collected and analyzed from 13 private,
      research, and regulatory groups. An effort was made to collect as much detail as
      possible about task, tool, and environmental and control conditions so as much
      information as possible could be garnered. There were considerable data gaps,
      particularly with regulatory agency data, that represented over half of the data
      set. There were 1374 personal quartz samples reported with a geometric mean of
      0.13 mg/m(3) and a GSD of 5.9. Descriptive statistics are reported by trade,
      task, tool, and data source type. Highest exposures were for abrasive blasters,
      surface and tuckpoint grinders, jackhammers, and rock drills. The sample period
      was important, with short-term samples (up to 2 hours) having considerably higher
      levels than midterm (2-6 hours) or longer (over 6 hours) samples. For nearly all
      exposure variables, a large portion of variable categories were at or over the
      quartz occupational exposure limit of 0.05 mg/m(3), including 8 of 8 trade, 13 of
      16 task, and 12 of 16 tool categories. The respiratory protection commonly used
      on construction sites is often inadequate for the exposures encountered. The data
      variability within task and tool was very large, with some very high exposures
      reported for a broad spectrum of tools. Further understanding of the conditions
      leading to high exposures will require more detailed documentation of the sample
      characteristics following database design recommendations or systematic surveys
      of exposure in this complex industry.

PMID- 16464819
TI  - Effect of temperature on permeation through air supply hoses.
AB  - Permeation of chemicals through the walls of air-supply hoses used with
      respirators is an underrecognized problem in industry. Transport of chemicals
      through the wall of a hose occurs in the same manner as through gloves and
      chemical suits, driven by the chemical concentration gradient, but for air-supply
      hoses the chemical evaporating inside the air-supply hose is inhaled. A simple
      method based on the mathematical equivalence of filling a homogeneous hose with a
      chemical, to immersing it in a chemical, has been developed. The method requires
      a short section of hose to be filled, plugged, and weighed at intervals to
      determine the breakthrough detection time and the cumulative permeation per
      meter. The method has been tested experimentally and calculations show that
      permeation of an air-line respirator hose could be a significant source of
      respiratory exposure, particularly for users of demand-type, supplied-air
      respirators.

PMID- 16464820
TI  - Accurate quantification of DNA methylation using combined bisulfite restriction
      analysis coupled with the Agilent 2100 Bioanalyzer platform.
AB  - DNA methylation is the best-studied epigenetic modification and describes the
      conversion of cytosine to 5-methylcytosine. The importance of this phenomenon is
      that aberrant promoter hypermethylation is a common occurrence in cancer and is
      frequently associated with gene silencing. Various techniques are currently
      available for the analysis of DNA methylation. However, accurate and reproducible
      quantification of DNA methylation remains challenging. In this report, we
      describe Bio-COBRA (combined bisulfite restriction analysis coupled with the
      Agilent 2100 Bioanalyzer platform), as a novel approach to quantitative DNA
      methylation analysis. The combination of a well-established method, COBRA, which
      interrogates DNA methylation via the restriction enzyme analysis of PCR-amplified
      bisulfite treated DNAs, with the Bioanalyzer platform allows for the rapid and
      quantitative assessment of DNA methylation patterns in large sample sets. The
      sensitivity and reproducibility of Bio-COBRA make it a valuable tool for the
      analysis of DNA methylation in clinical samples, which could aid in the
      development of diagnostic and prognostic parameters with respect to disease
      detection and management.

PMID- 16464821
TI  - Dimerization of the bacterial RsrI N6-adenine DNA methyltransferase.
AB  - Dimeric restriction endonucleases and monomeric modification methyltransferases
      were long accepted as the structural paradigm for Type II restriction systems.
      Recent studies, however, have revealed an increasing number of apparently dimeric
      DNA methyltransferases. Our initial characterization of RsrI methyltransferase
      (M.RsrI) was consistent with the enzyme functioning as a monomer, but,
      subsequently, the enzyme crystallized as a dimer with 1500 A2 of buried surface
      area. This result led us to re-examine the biochemical properties of M.RsrI. Gel
      shift studies of M.RsrI binding to DNA suggested that binding cooperativity
      targets hemimethylated DNA preferentially over unmethylated DNA. Size-exclusion
      chromatography indicated that the M.RsrI-DNA complex had a size and stoichiometry
      consistent with a dimeric enzyme binding to the DNA. Kinetic measurements
      revealed a quadratic relationship between enzyme velocity and concentration. Site
      directed mutagenesis at the dimer interface affected the kinetics and DNA-binding
      of the enzyme, providing support for a model proposing an active enzyme dimer. We
      also identified a conserved motif in the dimer interfaces of the beta-class
      methyltransferases M.RsrI, M.MboIIA and M2.DpnII. Taken together, these data
      suggest that M.RsrI may be part of a sub-class of MTases that function as dimers.

PMID- 16464823
TI  - The dicistronic RNA from the mouse LINE-1 retrotransposon contains an internal
      ribosome entry site upstream of each ORF: implications for retrotransposition.
AB  - Most eukaryotic mRNAs are monocistronic and translated by cap-dependent
      initiation. LINE-1 RNA is exceptional because it is naturally dicistronic,
      encoding two proteins essential for retrotransposition, ORF1p and ORF2p. Here, we
      show that sequences upstream of ORF1 and ORF2 in mouse L1 function as internal
      ribosome entry sites (IRESes). Deletion analysis of the ORF1 IRES indicates that
      RNA structure is critical for its function. Conversely, the ORF2 IRES localizes
      to 53 nt near the 3' end of ORF1, and appears to depend upon sequence rather than
      structure. The 40 nt intergenic region (IGR) is not essential for ORF2 IRES
      function or retrotransposition. Because of strong cis-preference for both
      proteins during L1 retrotransposition, correct stoichiometry of the two proteins
      can only be achieved post-transcriptionally. Although the precise stoichiometry
      is unknown, the retrotransposition intermediate likely contains hundreds of
      ORF1ps for every ORF2p, together with one L1 RNA. IRES-mediated translation
      initiation is a well-established mechanism of message-specific regulation, hence,
      unique mechanisms for the recognition and control of these two IRESes in the L1
      RNA could explain differences in translational efficiency of ORF1 and ORF2. In
      addition, translational regulation may provide an additional layer of control on
      L1 retrotransposition efficiency, thereby protecting the integrity of the genome.

PMID- 16464822
TI  - Molecular models for the tissue specificity of DNA mismatch repair-deficient
      carcinogenesis.
AB  - A common feature of all the known cancer genetic syndromes is that they
      predispose only to selective types of malignancy. However, many of the genes
      mutated in these syndromes are ubiquitously expressed, and influence seemingly
      universal processes such as DNA repair or cell cycle control. The tissue
      specificity of cancers that arise from malfunction of these apparently universal
      traits remains a key puzzle in cancer genetics. Mutations in DNA mismatch repair
      (MMR) genes cause the most common known cancer genetic syndrome, hereditary non
      polyposis colorectal cancer, and the fundamental biology of MMR is one of the
      most intensively studied processes in laboratories all around the world. This
      review uses MMR as a model system to understand mechanisms that may explain the
      selective development of tumors in particular cell types despite the universal
      nature of this process. We evaluate recent data giving insights into the specific
      tumor types that are attributable to defective MMR in humans and mice under
      different modes of inheritance, and propose models that may explain the spectrum
      of cancer types observed.

PMID- 16464824
TI  - Genome-wide prediction and characterization of interactions between transcription
      factors in Saccharomyces cerevisiae.
AB  - Combinatorial regulation by transcription factor complexes is an important
      feature of eukaryotic gene regulation. Here, we propose a new method for
      identification of interactions between transcription factors (TFs) that relies on
      the relationship of their binding sites, and we test it using Saccharomyces
      cerevisiae as a model system. The algorithm predicts interacting TF pairs based
      on the co-occurrence of their binding motifs and the distance between the motifs
      in promoter sequences. This allows investigation of interactions between TFs
      without known binding motifs or expression data. With this approach, 300
      significant interactions involving 77 TFs were identified. These included more
      than 70% of the known protein-protein interactions. Approximately half of the
      detected interacting motif pairs showed strong preferences for particular
      distances and orientations in the promoter sequences. These one dimensional
      features may reflect constraints on allowable spatial arrangements for protein
      protein interactions. Evidence for biological relevance of the observed
      characteristic distances is provided by the finding that target genes with the
      same characteristic distances show significantly higher co-expression than those
      without preferred distances. Furthermore, the observed interactions were dynamic:
      most of the TF pairs were not constitutively active, but rather showed variable
      activity depending on the physiological condition of the cells. Interestingly,
      some TF pairs active in multiple conditions showed preferences for different
      distances and orientations depending on the condition. Our prediction and
      characterization of TF interactions may help to understand the transcriptional
      regulatory networks in eukaryotic systems.

PMID- 16464825
TI  - Formation of the G-quadruplex and i-motif structures in retinoblastoma
      susceptibility genes (Rb).
AB  - The formation of G-quadruplex and i-motif structures in the 5' end of the
      retinoblastoma (Rb) gene was examined using chemical modifications, circular
      dichroism (CD) and fluorescence spectroscopy. It was found that substitutions of
      8-methylguanine at positions that show syn conformations in antiparallel G
      quadruplexes stabilize the structure in the G-rich strand. The complementary C
      rich 18mer forms an i-motif structure, as suggested by CD spectroscopy. Based on
      the C to T mutation experiments, C bases participated in the C-C+ base pair of
      the i-motif structure were determined. Experiments of 2-aminopurine (2-AP)
      substitution reveal that an increase of fluorescence in the G-quadruplex relative
      to duplex is attributed to unstacked 2-AP within the loop of G-quadruplex. The
      fluorescence experiments suggest that formation of the G-quadruplex and i-motif
      can compete with duplex formation. Furthermore, a polymerase arrest assay
      indicated that formation the G-quadruplex structure in the Rb gene acts as a
      barrier in DNA synthesis.

PMID- 16464826
TI  - Transcriptional activators in yeast.
AB  - Eukaryotic transcription activation domains (ADs) are not well defined on the
      proteome scale. We systematicallly tested approximately 6000 yeast proteins for
      transcriptional activity using a yeast one-hybrid system and identified 451
      transcriptional activators. We then determined their transcription activation
      strength using fusions to the Gal4 DNA-binding domain and a His3 reporter gene
      which contained a promoter with a Gal4-binding site. Among the 132 strongest
      activators 32 are known transcription factors while another 35 have no known
      function. Although zinc fingers, helix-loop-helix domains and several other
      domains are highly overrepresented among the activators, only few contain
      characterized ADs. We also found some striking correlations: the stronger the
      activation activity, the more acidic, glutamine-rich, proline-rich or asparagine
      rich the activators were. About 29% of the activators have been found previously
      to specifically interact with the transcription machinery, while 10% are known to
      be components of transcription regulatory complexes. Based on their
      transcriptional activity, localization and interaction patterns, at least six
      previously uncharacterized proteins are suggested to be bona fide transcriptional
      regulators (namely YFL049W, YJR070C, YDR520C, YGL066W/Sgf73, YKR064W and
      YCR082W/Ahc2).

PMID- 16464827
TI  - Core requirements for glmS ribozyme self-cleavage reveal a putative pseudoknot
      structure.
AB  - The glmS ribozyme is a self-cleaving RNA catalyst that resides in the 5'
      untranslated region of glmS mRNA in certain bacteria. The ribozyme is
      specifically activated by glucosamine-6-phosphate (GlcN6P), the metabolic product
      of the GlmS protein, and is thus proposed to provide a feedback mechanism of
      riboswitch regulation. Both phylogenetic and biochemical analyses of the glmS
      ribozyme have established a highly conserved core sequence and secondary
      structure required for GlcN6P-dependent self-cleavage. However, the high degree
      of nucleotide conservation offers few clues regarding the higher-order structural
      organization of the catalytic core. To further investigate core ribozyme
      structure, minimal 'consensus-type' glmS ribozymes that retain GlcN6P-dependent
      activity were produced. Mutational analyses of consensus-type glmS ribozymes
      support a model for core ribozyme folding through a pseudoknot structure formed
      by the interaction of two highly conserved sequence segments. Moreover, GlcN6P
      dependent function is demonstrated for bimolecular constructs in which substrate
      interaction with the ribozyme is minimally comprised of sequence representing
      that involved in putative pseudoknot formation. These studies suggest that the
      glmS ribozyme adopts an intricate multi-strand catalytic core through the
      formation of a pseudoknot structure, and provide a refined model for further
      considering GlcN6P interaction and GlcN6P-dependent ribozyme function.

PMID- 16464829
TI  - Interventional magnetic resonance imaging: an alternative to image guidance with
      ionising radiation.
AB  - At present, interventional procedures, such as stent placement, are performed
      under X-ray image guidance. Unfortunately with X-ray imaging, both patient and
      interventionalist are exposed to ionising radiation. Furthermore, X-ray imaging
      is lacking soft tissue contrast and is not capable of true 3-D displays of either
      interventional device or tissue morphology. Magnetic resonance imaging (MRI)
      offers excellent soft tissue contrast, 3-D acquisition techniques, as well as
      rapid image acquisition and reconstruction. Despite these advantages, MR-guided
      interventions are challenging owing to the limited access to the patient, strong
      magnetic and radio-frequency fields that require special interventional devices,
      inferior image frame rates and spatial resolution, and high MRI scanner noise.
      For MR-guided intravascular interventions, where access to the target organ is
      achieved through catheters, dedicated hardware and automated image slice
      positioning techniques have been developed. We illustrate that MR-guided renal
      embolisations can be performed in closed-bore high-field MR scanners.

PMID- 16464828
TI  - Identification of post-transcriptionally regulated Xenopus tropicalis maternal
      mRNAs by microarray.
AB  - Cytoplasmic control of the adenylation state of mRNAs is a critical post
      transcriptional process involved in the regulation of mRNAs stability and
      translational efficiency. The early development of Xenopus laevis has been a
      major model for the study of such regulations. We describe here a microarray
      analysis to identify mRNAs that are regulated by changes in their adenylation
      state during oogenesis and early development of the diploid frog Xenopus
      tropicalis. The microarray data were validated using qRT-PCR and direct analysis
      of the adenylation state of endogenous maternal mRNAs during the period studied.
      We identified more than 500 mRNAs regulated at the post-transcriptional level
      among the 3000 mRNAs potentially detected by the microarray. The mRNAs were
      classified into nine different adenylation behavior categories. The various
      adenylation profiles observed during oocyte maturation and early development and
      the analyses of 3'-untranslated region sequences suggest that previously
      uncharacterized sequence elements control the adenylation behavior of the newly
      identified mRNAs. These data should prove useful in identifying mRNAs with
      important functions during oocyte maturation and early development.

PMID- 16464830
TI  - Accreditation in radiation protection for cardiologists and interventionalists.
AB  - Training in radiation protection is widely recognised as one of the basic
      components of optimisation programmes for medical exposures. Occupational and
      patient radiation risks in interventional radiology can be quite high and
      international bodies have shown concern on this item. Following recommendations
      of the International Commission on Radiological Protection and in accordance with
      the European Directive on medical exposures, some initiatives for training in
      radiation protection took place in Spain and Luxembourg. These provided
      practitioners of interventional radiology adequate theoretical and practical
      training in radiation protection. The main outcome of the pilot courses organised
      to this end is discussed, concluding its suitability to implement the European
      Directive in practice.

PMID- 16464831
TI  - Review of image quality standards to control digital X-ray systems.
AB  - A literature review was carried out on quality criteria for the evaluation of
      image quality for interventional radiology, digital subtraction angiography,
      computed radiography and direct digital radiography systems. Existing national
      and international standards were also reviewed. Recommendations for image quality
      standards for digital X-ray systems are proposed.

PMID- 16464832
TI  - Bulgarian experience in the establishment of reference dose levels and
      implementation of a quality control system in diagnostic radiology.
AB  - Results from a Bulgarian patient dose survey in diagnostic radiology are
      presented. Reference levels for entrance surface dose (ESD) were 0.9 mGy for
      chest radiography (PA), 30 mGy for lumbar spine (Lat), 10 mGy for pelvis, 5 mGy
      for skull (AP), 3 mGy for skull (Lat) and 13 mGy for mammography. Quality control
      (QC) programmes were proposed for various areas of diagnostic radiology. Film
      processing QC warranted special attention. Proposed QC programmes included
      parameters to be tested, level of expertise needed and two action levels:
      remedial and suspension. Programmes were tested under clinical conditions to
      assess initial results and draw conclusions for further QC system development. On
      the basis of international experience, measurement protocols were developed for
      all parameters tested. QC equipment was provided as part of the PHARE project. A
      future problem for QC programme implementation may be the small number of medical
      physics experts in diagnostic radiology.

PMID- 16464833
TI  - Does digital imaging decrease patient dose? A pilot study and review of the
      literature.
AB  - The potential for decreasing patient dose is one of the main arguments for the
      justification of the cost of digital imaging equipment. However, the literature
      review with respect to patient doses using digital imaging modalities, presents
      conflicting results. During this study, patients' entrance surface doses were
      measured for three simple radiographic examinations, in European centres equipped
      with a computed radiography digital system. Results showed that doses between
      centres varied from 30% for chest LAT to 250% for chest PA examination. With the
      digital image quality criteria still under discussion, and with the post
      processing parameters and/or image documentations varying, any dose comparisons
      between conventional/digital systems, as well as dose comparisons between
      different centre using digital units, are difficult. Clinical trials are required
      in order to define reference levels associated with quality of digital image
      necessary to address specific clinical requirements.

PMID- 16464834
TI  - Characteristics of dosemeter types for skin dose measurements in practice.
AB  - A growing number of papers report deterministic effects in the skin of patients
      who have undergone interventional radiological procedures. Dose measurements, and
      especially skin dose measurements, are therefore increasingly important. Methods
      and acceptable dosemeters are, however, not clearly defined. This paper is the
      result of a literature overview with regard to assessing the entrance skin dose
      during radiological examinations by putting a dosemeter on the patient's skin.
      The relevant intrinsic characteristics, as well as some examples of clinical use
      of the different detector types, are presented. In this respect,
      thermoluminescence, scintillation, semiconductor and film dosemeters are
      discussed and compared with respect to their practical use.

PMID- 16464835
TI  - Evaluation of methods to estimate the patient dose in interventional radiology.
AB  - Dosimetric methods used for interventional and diagnostic radiology are reviewed
      and evaluated, including terms, quantities, equipment, calibration and
      measurements. Measurement of local skin dose and estimation of maximum local skin
      dose are emphasised. Aspects related to dosimetry in computed tomography and to
      methods of determining organ and tissue doses are not considered.

PMID- 16464836
TI  - Beam characterisation of the KIRAMS electron microbeam system.
AB  - An electron microbeam system has been installed at the Korea Institute of
      Radiological and Medical Sciences (KIRAMS) for use in radiation biology studies.
      The electron beam is produced from a commercial electron gun, and the beam size
      is defined by a 5 microm diameter pinhole. Beam energy can be varied in the range
      of 1-100 keV, covering a range of linear energy transfer from 0.4 to 12.1 keV
      microm-1. The micrometer-sized electron beam selectively irradiates cells
      cultured in a Mylar-bottomed dish. The positioning of target cells one by one
      onto the beam exit is automated, as is beam shooting. The electron beam entering
      the target cells has been calibrated using a Passivated Implanted Planar Silicon
      (PIPS) detector. This paper describes the KIRAMS microbeam cell irradiation
      system and its beam characteristics.

PMID- 16464837
TI  - Sensitivity loss of Lif:Mg,Cu,P thermoluminescence dosemeters caused by oven
      annealing.
AB  - LiF:Mg,Cu,P is a very sensitive thermoluminescence material that can be used for
      personal dosimetry in radiology. But if this material is heated too much during
      annealing or reading it quickly loses its sensitivity. This study shows that an
      annealing oven in wide use can cause thermal damage to the dosemeters owing to
      inhomogeneous temperature distribution in the annealing tray. At annealing
      temperatures>240 degrees C, differences of only 1 degrees C lead to significant
      losses of sensitivity. Therefore, it is necessary to measure the distribution of
      temperature in the annealing tray for correct placement of the dosemeters in the
      tray.

PMID- 16464838
TI  - Release criteria from hospitals of 131I thyrotoxicosis therapy patients in
      developing countries--case study.
AB  - The current release limit, recommended by the International Atomic Energy Agency
      (IAEA)(1), from hospitals of patients undergoing 131I thyrotoxicosis therapy is
      approximately 1100 MBq (approximately 30 mCi). Owing to the difference in socio
      economic conditions, literacy rate, family system, etc., this release limit may
      not be applicable in most of the developing countries like Pakistan. Therefore,
      the prime objective of this case study was to re-evaluate the release criteria
      for 131I thyrotoxicosis therapy patients by taking into account their lifestyle,
      economic conditions and other facilities such as availability of private/public
      transport, etc. In this context, systematic studies were carried out and 50
      patients (i.e. 35 outpatients and 15 inpatients) at the Nuclear Medicine Oncology
      and Radiotherapy Institute (NORI), Islamabad, were studied. Exposure rate at the
      surface of the body and at a distance of 1 m from the standing patient was
      measured. Results obtained from this study showed that the dose equivalent
      delivered by these patients to their family members (particularly children) and
      general public was higher than annual dose limits recommended by the
      International Commission for Radiation Protection in their report ICRP
      Publication 60(2). In the light of this study, it is recommended that the release
      activity limit of approximately 370 MBq (or dose rate level of approximately 10
      microSv h-1 at 1 m from the patient) be adopted instead of approximately 1100 MBq
      in developing countries like Pakistan.

PMID- 16464839
TI  - Towards a proposition of a diagnostic (dose) reference level for mammographic
      acquisitions in breast screening measurements in Belgium.
AB  - A diagnostic reference level (DRL) is a dose level for a typical X-ray
      examination of a group of patients with standard body sizes and for broadly
      defined types of equipment. These levels are expected not to be exceeded for
      standard procedures when good and normal practice regarding diagnostic and
      technical performance is applied. In this paper, we have calculated DRLs for
      screening mammography in Belgium. The 95th percentile of the mean average
      glandular dose is 2.46 mGy. The DRL based on polymethyl methacrylate (PMMA)
      measurements was 2.08 mGy. Correlation coefficient (R) between doses from patient
      studies and phantom studies was 0.90, with an average underestimation of the
      phantom measurements of 15% for systems that use only Mo/Mo anode/filter. For the
      centres that use other anode/filters, there is not enough scientific evidence
      that a single phantom measurement of a standard PMMA block is representative for
      the patient dose.

PMID- 16464840
TI  - Quality assurance (QA) procedures for software: evaluation of an ADC quality
      system.
AB  - Image viewing and processing software in computed radiography manipulates image
      contrast in such a way that all relevant image features are rendered to an
      appropriate degree of visibility, and improves image quality using enhancement
      algorithms. The purpose of this study was to investigate procedures for the
      quality assessment of image processing software for computed radiography with the
      use of existing test objects and to assess the influence that processing
      introduces on physical image quality characteristics. Measurements of high
      contrast resolution, low-contrast resolution, spatial resolution, greyscale
      (characteristic curve) and geometric distortion were performed 'subjectively' by
      three independent observers and 'objectively' by the use of criteria based on
      pixel intensity values. Results show quality assessment is possible without the
      need for human evaluators, using digital images. It was discovered that the
      processing software evaluated in this study was able to improve some aspects of
      image quality, without introducing geometric distortion.

PMID- 16464841
TI  - Mammographic screening: is the benefit worth the risk?
AB  - Justification of medical exposures is a fundamental principle of radiation
      protection. This principle applies to mammographic screening, both for the
      screened population and at an individual level. The benefit of mammographic
      screening may be considered to be the number of cancers detected or lives saved
      by breast screening. The risk is the hypothetical number of fatal cancers induced
      by the use of ionising radiation in screening mammography. Benefit can be deduced
      from the cancer detection rate in the NHS Breast Screening Programme. The number
      of additional lives saved by the intervention of a screening programme may be
      deduced from knowledge of the change in tumour size, stage and nodal status (and
      hence prognosis) in women with screening detected breast cancers compared with
      symptomatic women before screening. Calculations of benefit risk ratios to the UK
      population have been performed. It is concluded that breast screening is
      justified in radiation protection terms.

PMID- 16464842
TI  - Relevant training issues for introduction of digital radiology: results of a
      survey.
AB  - Council Directive 97/43/Euratom establishes the need for adequate training of
      radiology staff. The transition to digital radiology implies changes in various
      imaging aspects, which are not sufficiently covered by current institutional
      training programmes. This work aimed to assess how professionals, experienced in
      digital imaging, acquired their expertise and hence, what form institutional
      training should take. Within DIMOND III, a survey on training and resources was
      performed among radiology professionals. A lack of institutional education for
      digital radiology was found. In the transition to digital radiology, 30-35% train
      on the job and another 23-28% receive training from digital equipment vendors. A
      general agreement exists on the need for new quality criteria and strategies for
      dose management. Issues relevant for conventional/digital transition are only
      sparsely covered in EC training programmes. Based on these results, a set of
      training issues was produced, to be included in future European guidelines.

PMID- 16464843
TI  - Reducing pica by teaching children to exchange inedible items for edibles.
AB  - Assessment results indicated that pica exhibited by two boys with developmental
      disabilitieswas not associated with environmental contingencies. Consistent with
      previous research, an oral stimulation function was hypothesized. A related
      intervention that taught participants to exchange inedible items for edibles was
      developed. Findings showed that the intervention resulted in reductions in pica
      for both participants. When the interventionwas introduced across settings,
      reductions in pica were observed for one participant. However, additional
      training with alternative pica itemswas necessary to produce reductions in pica
      across settings with the second participant. Reductions in pica were maintained
      as the intervention was systematically thinned.

PMID- 16464844
TI  - The effects of self-management in general education classrooms on the
      organizational skills of adolescents with ADHD.
AB  - Self-management procedures have been used in school settings to successfully
      reduce problem behaviors, as well as to reinforce appropriate behavior. A
      multiple-baseline across participants design was applied in this study to
      evaluate the effects of using a self-management procedure to enhance the
      classroom preparation skills of secondary school students with attention-deficit/
      hyperactivity disorder (ADHD). Three male students enrolled in a public secondary
      school were selected for this study because teacher reports suggested that these
      students were insufficiently prepared for class and inconsistently completed
      assignments. The intervention involved training in self-management procedures
      focusing on the improvement of classroom preparation skills. Following the
      intervention, the training process was systematically faded. Results were
      consistent across the 3 participants in enhancing classroom preparation
      behaviors. Implications for practice and future research are discussed.

PMID- 16464845
TI  - Behavioral strategies for constructing nonviolent cultures with youth: a review.
AB  - Youth violence is widely recognized as a critical social issue in the United
      States, and many approaches to prevention have been developed in recent years.
      Emerging research suggests that only approaches that are deeply embedded in
      cultural, community, and organizational contexts are likely to be powerful enough
      to have a meaningful collective impact. No programs of this kind that are also
      truly practical and socially valid have yet reached a level where they can be
      regarded as well established, but data are beginning to appear that can guide
      community efforts. In this review, two classes of behavioral programming that
      appear promising as partial solutions to this need are identified: universal
      skills training and ecological strategies that focus on interlocking cultural
      practices. Progressive refinements in both are appearing through programs of
      developmental research. This paper reviews the state of the science in these
      efforts.

PMID- 16464846
TI  - The good behavior game: 1969-2002.
AB  - The Good Behavior Game (GBG), a type of interdependent group-oriented contingency
      management procedure, was first introduced in 1969 and has been used with
      overwhelming success in classrooms and other settings. Since its inception, the
      "game" has utilized team competition and peer influence combined with
      reinforcement procedures. It has been found to be popular, easy-to-use, time
      efficient, and widely applicable and versatile. This review describes the game
      and its numerous variations and adaptations, as well as empirical findings
      specific to the variety of target behaviors and participants to which it has been
      applied. In addition, different types of reinforcers used, information on
      consumer acceptance, and issues related to implementation are considered.

PMID- 16464848
TI  - A non-cleavable UmuD variant that acts as a UmuD' mimic.
AB  - UmuD(2) cleaves and removes its N-terminal 24 amino acids to form UmuD'(2), which
      activates UmuC for its role in UV-induced mutagenesis in Escherichia coli. Cells
      with a non-cleavable UmuD exhibit essentially no UV-induced mutagenesis and are
      hypersensitive to killing by UV light. UmuD binds to the beta processivity clamp
      ("beta") of the replicative DNA polymerase, pol III. A possible beta-binding
      motif has been predicted in the same region of UmuD shown to be important for its
      interaction with beta. We performed alanine-scanning mutagenesis of this motif
      ((14)TFPLF(18)) in UmuD and found that it has a moderate influence on UV-induced
      mutagenesis but is required for the cold-sensitive phenotype caused by elevated
      levels of wild-type UmuD and UmuC. Surprisingly, the wild-type and the beta
      binding motif variant bind to beta with similar K(d) values as determined by
      changes in tryptophan fluorescence. However, these data also imply that the
      single tryptophan in beta is in strikingly different environments in the presence
      of the wild-type versus the variant UmuD proteins, suggesting a distinct change
      in some aspect of the interaction with little change in its strength. Despite the
      fact that this novel UmuD variant is non-cleavable, we find that cells harboring
      it display phenotypes more consistent with the cleaved form UmuD', such as
      resistance to killing by UV light and failure to exhibit the cold-sensitive
      phenotype. Cross-linking and chemical modification experiments indicate that the
      N-terminal arms of the UmuD variant are less likely to be bound to the globular
      domain than those of the wild-type, which may be the mechanism by which this UmuD
      variant acts as a UmuD' mimic.

PMID- 16464847
TI  - Regulatory factor for X-box family proteins differentially interact with histone
      deacetylases to repress collagen alpha2(I) gene (COL1A2) expression.
AB  - Our studies indicate that the regulatory factor for X-box (RFX) family proteins
      repress collagen alpha2(I) gene (COL1A2) expression (Xu, Y., Wang, L., Buttice,
      G., Sengupta, P. K., and Smith, B. D. (2003) J. Biol. Chem. 278, 49134-49144; Xu,
      Y., Wang, L., Buttice, G., Sengupta, P. K., and Smith, B. D. (2004) J. Biol.
      Chem. 279, 41319-41332). In this study, we examined the mechanism(s) underlying
      the repression of collagen gene by RFX proteins. Two members of the RFX family,
      RFX1 and RFX5, associate with distinct sets of co-repressors on the collagen
      transcription start site in vitro. RFX5 specifically interacts with histone
      deacetylase 2 (HDAC2) and the mammalian transcriptional repressor (mSin3B),
      whereas RFX1 preferably interacts with HDAC1 and mSin3A. HDAC2 cooperates with
      RFX5 to down-regulate collagen promoter activity, whereas HDAC1 enhances
      inhibition of collagen promoter activity by RFX1. Interferon-gamma promotes the
      recruitment of RFX5/HDAC2/mSin3B to the collagen transcription start site but
      decreases the occupancy by RFX1/mSin3A as manifested by chromatin
      immunoprecipitation assay. RFX1 binds to the methylated collagen sequence with
      much higher affinity than unmethylated sequence, recruiting more HDAC1 and
      mSin3A. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, which
      inhibits DNA methylation, reduces RFX1/HDAC1 binding to the collagen
      transcription start site in chromatin immunoprecipitation assays. Finally, both
      RFX1 and RFX5 are acetylated in vivo. Trichostatin A stimulates the acetylation
      of RFX proteins and activates the collagen promoter activity. Collectively, our
      data strongly indicate two separate pathways for RFX proteins to repress collagen
      gene expression as follows: one for RFX5/HDAC2 in interferon-gamma-mediated
      repression, and the other for RFX1/HDAC1 in methylation-mediated collagen
      silencing.

PMID- 16464850
TI  - 6-Hydroxydopamine but not 1-methyl-4-phenylpyridinium abolishes alpha-synuclein
      anti-apoptotic phenotype by inhibiting its proteasomal degradation and by
      promoting its aggregation.
AB  - We established previously that alpha-synuclein displayed a protective anti
      apoptotic phenotype in neurons, mainly by down-regulating p53-dependent caspase-3
      activation (Alves da Costa, C., Ancolio, K., and Checler, F. (2000) J. Biol.
      Chem. 275, 24065-24069; Alves da Costa, C., Paitel, E., Vincent, B., and Checler,
      F. (2002) J. Biol. Chem. 277, 50980-50984). This function was abolished by
      Parkinson disease-linked pathogenic mutations and by the dopaminergic toxin, 6
      hydroxydopamine (6OH-DOPA) (Alves da Costa, C., Paitel, E., Vincent, B., and
      Checler, F. (2002) J. Biol. Chem. 277, 50980-50984). However, the mechanisms by
      which 6OH-DOPA interfered with alpha-synuclein function remained unclear. Here we
      showed that 6OH-DOPA prevents alpha-synuclein-mediated anti-apoptotic function by
      altering its degradation. Thus, 6OH-DOPA treatment of TSM1 neurons and SH-SY5Y
      neuroblastoma cells enhances endogenous alpha-synuclein-like immunoreactivity and
      inhibits the catabolism of endogenous and recombinant alpha-synucleins by
      purified 20 S proteasome. Furthermore, we demonstrated that 6OH-DOPA directly
      inhibits endogenous proteasomal activity in TSM1 and SH-SY5Y cells and also
      blocks purified proteasome activity in vitro. This inhibitory effect can be
      prevented by the anti-oxidant phenyl-N-butylnitrone. We also established that 6OH
      DOPA triggers the aggregation of recombinant alpha-synuclein in vitro. Therefore,
      we conclude that 6OH-DOPA abolishes alpha-synuclein anti-apoptotic phenotype by
      inhibiting its proteasomal degradation, thereby increasing its intracellular
      concentration and potential propensity to aggregation, the latter phenomenon
      being directly exacerbated by 6OH-DOPA itself. Interestingly, 1-methyl-4
      phenylpyridinium (MPP(+)), another toxin inducer of Parkinson disease-like
      pathology, does not affect alpha-synuclein protective function and fails to
      trigger aggregation of recombinant alpha-synuclein. Furthermore, MPP(+) does not
      alter cellular proteasomal activity, and only high concentrations of the toxin
      affect purified 20 S proteasome by a mechanism that remains insensitive to phenyl
      N-butylnitrone. The drastically distinct effects of 6OH-DOPA and MPP(+) on alpha
      synuclein function are discussed with respect to Parkinson disease pathology and
      animal models mimicking this pathology.

PMID- 16464851
TI  - Structure, function, and mechanism of the phenylacetate pathway hot dog-fold
      thioesterase PaaI.
AB  - The structure and biochemical function of the hot dog-fold thioesterase PaaI
      operative in the aerobic phenylacetate degradation pathway are examined. PaaI
      showed modest activity with phenylacetyl-coenzyme A, suggestive of a role in
      coenzyme A release from this pathway intermediate in the event of limiting
      downstream pathway enzymes. Minimal activity was observed with aliphatic acyl
      coenzyme A thioesters, which ruled out PaaI function in the lower phenylacetate
      pathway. PaaI was most active with ring-hydroxylated phenylacetyl-coenzyme A
      thioesters. The x-ray crystal structure of the Escherichia coli thioesterase is
      reported and analyzed to define the structural basis of substrate recognition and
      catalysis. The contributions of catalytic and substrate binding residues, thus,
      identified were examined through steady-state kinetic analysis of site-directed
      mutant proteins.

PMID- 16464852
TI  - Specific requirement for Bax, not Bak, in Myc-induced apoptosis and tumor
      suppression in vivo.
AB  - Bax and Bak comprise the mitochondrial gateway for apoptosis induced by diverse
      stimuli. Loss of both bax and bak is necessary to block cell death induced by
      such stimuli, indicating a great degree of functional overlap between Bax and
      Bak. Apoptosis is the major intrinsic pathway that limits the oncogenic potential
      of Myc. Using a switchable mouse model of Myc-induced apoptosis in pancreatic
      beta cells, we have shown that Myc induces apoptosis in vivo exclusively through
      Bax but not Bak. Furthermore, blockade of Myc-induced apoptosis by the
      inactivation of Bax, but not Bak, eliminates all restraints to the oncogenic
      potential of Myc, allowing the rapid and synchronous progression of invasive,
      angiogenic tumors.

PMID- 16464853
TI  - Active metabolite of atorvastatin inhibits membrane cholesterol domain formation
      by an antioxidant mechanism.
AB  - The advanced atherosclerotic lesion is characterized by the formation of
      microscopic cholesterol crystals that contribute to mechanisms of inflammation
      and apoptotic cell death. These crystals develop from membrane cholesterol
      domains, a process that is accelerated under conditions of hyperlipidemia and
      oxidative stress. In this study, the comparative effects of hydroxymethylglutaryl
      CoA (HMG-CoA) reductase inhibitors (statins) on oxidative stress-induced
      cholesterol domain formation were tested in model membranes containing
      physiologic levels of cholesterol using small angle x-ray diffraction approaches.
      In the absence of HMG-CoA reductase, only the atorvastatin active o-hydroxy
      metabolite (ATM) blocked membrane cholesterol domain formation as a function of
      oxidative stress. This effect of ATM is attributed to electron donation and
      proton stabilization mechanisms associated with its phenoxy group located in the
      membrane hydrocarbon core. ATM inhibited lipid peroxidation in human low density
      lipoprotein and phospholipid vesicles in a dose-dependent manner, unlike its
      parent and other statins (pravastatin, rosuvastatin, simvastatin). These findings
      indicate an atheroprotective effect of ATM on membrane lipid organization through
      a potent antioxidant mechanism.

PMID- 16464854
TI  - Modifications of H3 and H4 during chromatin replication, nucleosome assembly, and
      histone exchange.
AB  - Histone posttranslational modifications that accompany DNA replication,
      nucleosome assembly, and H2A/H2B exchange were examined in human tissue culture
      cells. Through microsequencing analysis and chromatin immunoprecipitation, it was
      found that a subset of newly synthesized H3.2/H3.3 is modified by acetylation and
      methylation at sites that correlate with transcriptional competence.
      Immunoprecipitation experiments suggest that cytosolic predeposition complexes
      purified from cells expressing FLAG-H4 contain H3/H4 dimers, not tetramers.
      Studies of the deposition of newly synthesized H2A/H2B onto replicating and
      nonreplicating chromatin demonstrated that H2A/H2B exchange takes place in
      chromatin regions that contain acetylated H4; however, there is no single pattern
      of H4 acetylation that accompanies exchange. H2A/H2B exchange is also largely
      independent of the deposition of replacement histone variant, H3.3. Finally,
      immunoprecipitation of nucleosomes replicated in the absence of de novo
      nucleosome assembly showed that histone modifications do not prevent the transfer
      of parental histones to newly replicated DNA and thus have the potential to serve
      as means of epigenetic inheritance. Our experiments provide an in-depth analysis
      of the "histone code" associated with chromatin replication and dynamic histone
      exchange in human cells.

PMID- 16464855
TI  - Molecular properties of adult mouse gastric and intestinal epithelial progenitors
      in their niches.
AB  - We have sequenced 36,641 expressed sequence tags from laser capture
      microdissected adult mouse gastric and small intestinal epithelial progenitors,
      obtaining 4031 and 3324 unique transcripts, respectively. Using Gene Ontology
      (GO) terms, each data set was compared with cDNA libraries from intact adult
      stomach and small intestine. Genes in GO categories enriched in progenitors were
      filtered against genes in GO categories represented in hematopoietic, neural, and
      embryonic stem cell transcriptomes and mapped onto transcription factor networks,
      plus canonical signal transduction and metabolic pathways. Wnt/beta-catenin,
      phosphoinositide-3/Akt kinase, insulin-like growth factor-1, vascular endothelial
      growth factor, integrin, and gamma-aminobutyric acid receptor signaling cascades,
      plus glycerolipid, fatty acid, and amino acid metabolic pathways are among those
      prominently represented in adult gut progenitors. The results reveal shared as
      well as distinctive features of adult gut stem cells when compared with other
      stem cell populations.

PMID- 16464856
TI  - Cytokines promote Wnt signaling and inflammation and impair the normal
      differentiation and lipid accumulation in 3T3-L1 preadipocytes.
AB  - Obesity with enlarged fat cells is associated with high local concentrations of
      interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) in the adipose
      tissue. We examined the effects of this inflammatory state on 3T3-L1 preadipocyte
      development and differentiation to mature adipose cells. Both IL-6 and TNFalpha
      impaired the normal differentiation pattern and lipid accumulation. However, IL-6
      allowed a normal early induction of differentiation with inhibition of Wnt10b and
      Pref-1, whereas expression of CCAAT/enhancer-binding protein alpha, in contrast
      to peroxisome proliferator-activated receptor gamma, was markedly reduced.
      TNFalpha also allowed a normal early induction of differentiation, whereas the
      terminal differentiation to adipose cells was completely prevented. However, both
      cytokines induced an inflammatory phenotype of the cells but with different
      profiles. Remarkably, both IL-6 and TNFalpha maintained and augmented the
      canonical Wnt signaling associated with low axin and high low density lipoprotein
      receptor-related protein (LRD), Dishevelled, and beta-catenin levels. TNFalpha,
      but not IL-6, activated Wnt10b expression, whereas IL-6 increased the apparent
      phosphorylation of Dishevelled. Thus, both IL-6 and TNFalpha prevent the normal
      development of preadipocytes to fully differentiated adipose cells and, instead,
      promote an inflammatory phenotype of the adipocytes. These results provide an
      explanation as to why obesity and diabetes are associated with both local and
      systemic inflammation, insulin resistance, and ectopic lipid accumulation.

PMID- 16464857
TI  - Protein O-fucosyltransferase 2 adds O-fucose to thrombospondin type 1 repeats.
AB  - O-Fucose is an unusual form of glycosylation found on epidermal growth factor
      like (EGF) repeats and thrombospondin type 1 repeats (TSRs) in many secreted and
      transmembrane proteins. Recently O-fucose on EGF repeats was shown to play
      important roles in Notch signaling. In contrast, physiological roles for O-fucose
      on TSRs are unknown. In the accompanying paper (Luo, Y., Nita-Lazar, A., and
      Haltiwanger, R. S. (2006) J. Biol. Chem. 281, 9385-9392), we demonstrated that an
      enzyme distinct from protein O-fucosyltransferase 1 adds O-fucose to TSRs. A
      known homologue of O-fucosyltransferase 1 is putative protein O
      fucosyltransferase 2. The cDNA sequence encoding O-fucosyltransferase 2 was
      originally identified during a data base search for fucosyltransferases in
      Drosophila. Like O-fucosyltransferase 1, O-fucosyltransferase 2 is conserved from
      Caenorhabditis elegans to humans. Although O-fucosyltransferase 2 was assumed to
      be another protein O-fucosyltransferase, no biochemical characterization existed
      supporting this contention. Here we show that RNAi-mediated reduction of the O
      fucosyltransferase 2 message significantly decreased TSR-specific O
      fucosyltransferase activity in Drosophila S2 cells. We also found that O
      fucosyltransferase 2 is predominantly localized in the endoplasmic reticulum
      compartment of these cells. Furthermore, we expressed recombinant Drosophila O
      fucosyltransferase 2 and showed that it O-fucosylates TSRs but not EGF repeats in
      vitro. These results demonstrate that O-fucosyltransferase 2 is in fact a TSR
      specific O-fucosyltransferase.

PMID- 16464858
TI  - Two distinct pathways for O-fucosylation of epidermal growth factor-like or
      thrombospondin type 1 repeats.
AB  - Epidermal growth factor-like (EGF) repeats and thrombospondin type 1 repeats
      (TSRs) are both small cysteine-knot motifs known to be O-fucosylated. The enzyme
      responsible for the addition of O-fucose to EGF repeats, protein O
      fucosyltransferase 1 (POFUT1), has been identified and shown to be essential in
      Notch signaling. Fringe, an O-fucose beta1,3-N-acetylglucosaminyltransferase,
      elongates O-fucose on specific EGF repeats from Notch to form a disaccharide that
      can be further elongated to a tetrasaccharide. TSRs are found in many
      extracellular matrix proteins and are involved in protein-protein interactions.
      The O-fucose moiety on TSRs can be further elongated with glucose to form a
      disaccharide. The discovery of O-fucose on TSRs raised the question of whether
      POFUT1, or a different enzyme, adds O-fucose to TSRs. Here we demonstrate the
      existence of a TSR-specific O-fucosyltransferase distinct from POFUT1. Similar to
      POFUT1, the novel TSR-specific O-fucosyltransferase is a soluble enzyme that
      requires a properly folded TSR as an acceptor substrate. In addition, we found
      that a previously identified fucose-specific beta1,3-glucosyltransferase adds
      glucose to O-fucose on TSRs, but it does not modify O-fucose on an EGF repeat.
      Similarly, Lunatic fringe, Manic fringe, and Radical fringe are all capable of
      modifying O-fucose on an EGF repeat, but not on a TSR. Taken together, these
      results suggest that two distinct O-fucosylation pathways exist in cells, one
      specific for EGF repeat and the other for TSRs.

PMID- 16464859
TI  - Nitric oxide-dependent negative feedback of PARP-1 trans-activation of the
      inducible nitric-oxide synthase gene.
AB  - Nitric oxide (NO) participates in a variety of physiologic and pathophysiologic
      processes in diverse tissues, including the kidney. Although mechanisms for
      cytokine induction of inducible nitric-oxide synthase (iNOS) have been
      increasingly clarified, the controls for termination of NO production remain
      unclear. Because excessive NO production can be cytotoxic to host cells, feedback
      inhibition of iNOS transcription would represent a means of cytoprotection. Many
      of the cGMP-independent functions of NO are mediated by S-nitrosylation of
      cysteine thiols of target proteins. We hypothesized that NO-mediated S
      nitrosylation of transcription factors might serve to feedback inhibit their
      trans-activation potential and deactivate iNOS gene transcription. Transient
      transfection of murine mesangial cells with iNOS promoter deletion-luciferase
      constructs revealed the region -915 to -849 to be NO sensitive with respect to IL
      1beta-induced promoter activity. In vitro DNase I footprinting identified a
      footprint at -865/-842 in the absence of NO, but not in the presence of
      endogenous or exogenously delivered NO. Southwestern blotting using this probe
      coupled with partial peptide sequencing of the protein bands revealed that
      poly(ADP-ribose) polymerase isoform 1 (PARP-1) bound the probe in a sequence
      specific manner. Gel shift/supershift experiments and chromatin
      immunoprecipitation assay analysis confirmed this binding in vitro and in vivo.
      Functionally, mutation of the -859/-850 site to prevent PARP-1 binding or PARP-1
      knockdown by RNA interference relieved the inhibitory effects of NO on iNOS
      promoter activity. Biotin-switch assays and co-immunoprecipitation with an anti
      nitrocysteine antibody indicated that PARP-1 was S-nitrosylated. We conclude that
      NO feedback inhibits iNOS gene transcription by S-nitrosylating the trans
      activator PARP-1 and decreasing its binding and/or action at the iNOS promoter.

PMID- 16464860
TI  - Methylglyoxal as a signal initiator for activation of the stress-activated
      protein kinase cascade in the fission yeast Schizosaccharomyces pombe.
AB  - Methylglyoxal (MG) is a typical 2-oxoaldehyde derived from glycolysis. We have
      recently found that MG activates transcription factors such as Yap1 and Msn2, and
      triggers a Hog1 mitogen-activated protein kinase cascade in Saccharomyces
      cerevisiae. Regarding the activation of Hog1 by MG, we found that Sln1, an
      osmosensor possessing histidine kinase activity, functions as a sensor of MG
      (Maeta, K., Izawa, S., and Inoue, Y. (2005) J. Biol. Chem. 280, 253-260). To gain
      further insight into the role of MG as a signal initiator, here we analyze the
      response of Schizosaccharomyces pombe to extracellular MG. Spc1, a stress
      activated protein kinase (SAPK), was phosphorylated following the treatment with
      MG. No phosphorylation was observed in a wis1Delta mutant. The His-to-Asp
      phosphorelay system consisting of three histidine kinases (Phk1, Phk2, and Phk3),
      a phosphorelay protein (Spy1), and a response regulator (Mcs4) exists upstream of
      the Spc1-SAPK pathway. The phosphorylation of Spc1 following MG treatment was
      observed in phk1Deltaphk2Deltaphk3Delta and spy1Delta cells, but not in mcs4Delta
      cells. These results suggest that S. pombe has an alternative module(s) that
      directs the MG signal to the SAPK pathway via Mcs4. Additionally, we found that
      the transcription factor Pap1 is concentrated in the nucleus in response to MG,
      independent of the Spc1-SAPK pathway.

PMID- 16464861
TI  - Heterogeneous nuclear ribonucleoprotein-A2/B1 modulate collagen prolyl 4
      hydroxylase, alpha (I) mRNA stability.
AB  - Collagen prolyl 4-hydroxylase (C-P4H) alpha-subunit is of regulatory importance
      in the assembling of C-P4H tetramers, which are necessary for the hydroxylation
      of procollagen chains. Change in collagen expression by hypoxia or iron
      diminishment is a significant issue in extracellular matrix remodeling. It was
      proposed that C-P4H-alpha (I) is regulated at the posttrancriptional level under
      these conditions. Here we report that the induction of C-P4H-alpha (I) in human
      fibrosarcoma cells HT1080 by the iron chelator 2,2-dipyridyl is predominantly
      caused by an enhancement of mRNA stability. This effect is mediated by an
      increased synthesis and binding of heterogeneous nuclear ribonucleoprotein
      (hnRNP)-A2/B1, which interacts with a (U)(16) element located in the 3'
      untranslated region of C-P4H-alpha (I) mRNA. Luciferase reporter gene assays
      depending on C-P4H-alpha (I) 3'-untranslated region and co-transfection with
      hnRNP-A2/B1 provide evidence that the (U)(16) element is necessary and sufficient
      for posttranscriptional control of C-P4H-alpha (I) synthesis under the analyzed
      conditions. Further indication for the significance of hnRNP-A2/B1 in C-P4H-alpha
      (I) induction was obtained by micro array experiments. In a data set representing
      686 independent physiological conditions, we found a significant positive
      correlation between hnRNP-A2/B1 and C-P4H-alpha (I) mRNAs.

PMID- 16464862
TI  - A specific mechanomodulatory role for p38 MAPK in embryonic joint articular
      surface cell MEK-ERK pathway regulation.
AB  - Mechanisms regulating cell behavior and extracellular matrix composition in
      response to mechanical stimuli remain unresolved. Our previous studies have
      established that the MEK-ERK cascade plays a specific role in the mechano
      dependent joint formation process by promoting the assembly of pericellular
      matrices reliant upon hyaluronan (HA) for their integrity. Here we demonstrate:
      (i) novel cross-talk between p38 MAPK and MEK-ERK signaling pathways that is
      specific for mechanical stimuli and (ii) a role for p38 MAPK in facilitating HA
      production by cells derived from the articular surface of embryonic chick
      tibiotarsal joints. We find that p38 MAPK blockade restricts pericellular
      assembly of HA-rich matrices and reduces basal as well as mechanical strain
      induced release of HA. p38 MAPK blockers potentiated early strain-induced
      increases but restricted sustained increases in MEK/ERK phosphorylation at later
      times; c-Fos hyperphosphorylation at threonine 325 was found to parallel this p38
      MAPK-mediated modulation of ERK activation. In contrast, p38 MAPK inhibitors had
      no detectable effect on the ERK activation induced by fibroblast growth factor 2
      or pervanadate, a phosphatase inhibitor, and MEK inhibitors did not influence p38
      MAPK phosphorylation, confirming both the specificity and unidirectionality of
      p38 MAPK-ERK cross-talk. Immunochemical and immunoblotting studies revealed
      constitutive p38 MAPK activation in cells at, or derived from, developing
      articular joint surfaces. Unlike the MEK-ERK pathway, however, p38 MAPK was not
      further stimulated by mechanical stimulation in vitro. Thus, p38 MAPK
      specifically facilitates ERK activation and downstream signaling in response to
      mechanical stimuli. These results suggest that constitutively active p38 MAPK
      serves an essential, permissive role in mechanically induced changes in ERK
      activation and in the accumulation of HA-rich extracellular matrices that serve a
      key role in joint development.

PMID- 16464863
TI  - The role of Drosophila ninaG oxidoreductase in visual pigment chromophore
      biogenesis.
AB  - We previously reported (Sarfare, S., Ahmad, S. T., Joyce, M. V., Boggess, B., and
      O'Tousa, J. E. (2005) J. Biol. Chem. 280, 11895-11901) that the Drosophila ninaG
      gene encodes an oxidoreductase involved in the biosynthesis of the (3S)-3
      hydroxyretinal serving as chromophore for Rh1 rhodopsin and that ninaG mutant
      flies expressing Rh4 as the major opsin accumulate large amounts of a different
      retinoid. Here, we show that this unknown retinoid is 11-cis-3-hydroxyretinol.
      Reversed phase high performance liquid chromatography coupled with a photodiode
      array UV-visible absorbance detector and mass spectrometer revealed a major
      product eluting at a retention time, t(r), of 3.5 min with a lambda(max) of
      approximately 324 nm and with a base peak in the mass spectrum at m/z 285. These
      observations are identical with those of the 3-hydroxyretinol standard. The base
      peak in the electrospray ionization mass spectrum arises from the loss of a water
      molecule from the protonated molecule at m/z 303 because of fragmentation in the
      ion source. These results suggest that 11-cis-3-hydroxyretinol is an intermediate
      required for chromophore biogenesis in Drosophila. We further show that ninaG
      mutants fed on retinal as the sole source of vitamin A are able to synthesize 3
      hydroxyretinoids. Thus, the NinaG oxidoreductase is not responsible for the
      initial hydroxylation of the retinal ring but rather acts in a subsequent step in
      chromophore production. These data are used to review chromophore biosynthesis
      and propose that NinaG acts in the conversion of (3R)-3-hydroxyretinol to the 3S
      enantiomer.

PMID- 16464864
TI  - Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins
      tau and alpha-synuclein.
AB  - Sumoylation is an important post-translational modification that provides a rapid
      and reversible means for controlling the activity, subcellular localization, and
      stability of target proteins. We have examined the covalent attachment of the
      small ubiquitin-like modifier (SUMO) proteins to tau and alpha-synuclein, two
      natively unfolded proteins that define several neurodegenerative diseases. Both
      brain proteins were preferentially modified by SUMO1, as compared with SUMO2 or
      SUMO3. Tau contains two SUMO consensus sequences, and mutational analyses
      identified Lys(340) as the major sumoylation site. Although both tau and alpha
      synuclein are targets for proteasomal degradation, only tau sumoylation was
      affected by inhibitors of the proteasome pathway. Tau is a microtubule-associated
      protein, whose ability to bind and stabilize microtubules is negatively regulated
      by phosphorylation. Treatment with the phosphatase inhibitor, okadaic acid, or
      the microtubule depolymerizing drug, colchicine, up-regulated tau sumoylation.
      This suggests that SUMO modification may preferentially target a free soluble
      pool of the substrate. These findings revealed a new, possibly regulatory,
      modification of tau and alpha-synuclein that may also have implications for their
      pathogenic roles in neurodegenerative diseases.

PMID- 16464866
TI  - Identification and functional characterization of a presqualene diphosphate
      phosphatase.
AB  - Presqualene diphosphate (PSDP) is a bioactive lipid that rapidly remodels to
      presqualene monophosphate (PSMP) upon cell activation (Levy, B. D., Petasis, N.
      A., and Serhan, C. N. (1997) Nature 389, 985-990). Here, we have identified and
      characterized a phosphatase that converts PSDP to PSMP. Unlike the related
      polyisoprenyl phosphate farnesyl diphosphate (FDP), PSDP was not a substrate for
      type 2 lipid phosphate phosphohydrolases. PSDP phosphatase activity was
      identified in activated human neutrophil (PMN) extracts and partially purified in
      the presence of Nonidet P-40 with gel filtration and anion exchange
      chromatography. Peptide sequencing of a candidate phosphatase was consistent with
      phosphatidic acid phosphatase domain containing 2 (PPAPDC2), an uncharacterized
      protein that contains a lipid phosphate phosphohydrolase consensus motif.
      Recombinant PPAPDC2 displayed diphosphate phosphatase activity with a substrate
      preference for PSDP > FDP > phosphatidic acid. PPAPDC2 activity was independent
      of Mg(2+) and optimal at pH 7.0 to 8.0. Incubation of [(14)C]FDP with recombinant
      human squalene synthase led to [(14)C]PSDP and [(14)C]squalene formation, and in
      the presence of PPAPDC2, [(14)C]PSMP was generated from [(14)C]PSDP. PPAPDC2 mRNA
      was detected in human PMN, and is widely expressed in human tissues. Together,
      these findings indicate that PPAPDC2 in human PMN is the first lipid phosphate
      phosphohydrolase identified for PSDP. Regulation of this activity of the enzyme
      may have important roles for PMN activation in innate immunity.

PMID- 16464865
TI  - TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1
      ubiquitin ligase.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized
      by hamartoma formation in various organs. Two genes responsible for the disease,
      TSC1 and TSC2, have been identified. The TSC1 and TSC2 proteins, also called
      hamartin and tuberin, respectively, have been shown to regulate cell growth
      through inhibition of the mammalian target of rapamycin pathway. TSC1 is known to
      stabilize TSC2 by forming a complex with TSC2, which is a GTPase-activating
      protein for the Rheb small GTPase. We have identified HERC1 as a TSC2-interacting
      protein. HERC1 is a 532-kDa protein with an E3 ubiquitin ligase homology to E6AP
      carboxyl terminus (HECT) domain. We observed that the interaction of TSC1 with
      TSC2 appears to exclude TSC2 from interacting with HERC1. Disease mutations in
      TSC2, which result in its destabilization, allow binding to HERC1 in the presence
      of TSC1. Our study reveals a potential molecular mechanism of how TSC1 stabilizes
      TSC2 by excluding the HERC1 ubiquitin ligase from the TSC2 complex. Furthermore,
      these data reveal a possible biochemical basis of how certain disease mutations
      inactivate TSC2.

PMID- 16464867
TI  - Domain analysis of a groundnut calcium-dependent protein kinase: nuclear
      localization sequence in the junction domain is coupled with nonconsensus calcium
      binding domains.
AB  - The signature of calcium-dependent protein kinases (CDPKs) is a C-terminal
      calmodulin-like domain (CaMLD) with four consensus calcium-binding sites. A
      junction domain (JD) joins the kinase with CaMLD and interacts with them through
      its autoinhibitory and CaMLD binding subdomains, respectively. We noted several
      CDPKs additionally have a bipartite nuclear localization signal (NLS) sequence as
      a subdomain in their JD, and this feature is obligatorily coupled with the
      absence of consensus calcium-binding sites in their respective CaMLDs. These
      predicted features are substantiated by undertaking investigations on a CDPK
      (gi:67479988) isolated from cultured groundnut (Arachis hypogea) cells. This
      kinase can bind 3.1 mol of Ca(2+) under saturating conditions with a considerably
      high K(d) of 392 mum as compared with its canonical counterparts. CD
      spectroscopic analysis, however, indicates the intramolecular structural changes
      accompanied with calcium binding to be similar to canonical CDPKs. Attesting to
      the presence of NLS in the JD, the endogenous kinase is localized in the nucleus
      of osmotically stressed Arachis cells, and in vitro binding assays indicate the
      NLS in the JD to interact with nuclear transport factors of the importin family.
      Homology modeling also indicates the feasibility of interaction of importins with
      the NLS present in the JD of such CDPKs in their activated form. The possible
      significance of obligatory coupling between the presence of NLS in the junction
      domain and atypical calcium binding properties of these CDPKs is discussed in the
      light of the known mechanisms of activation of these kinases.

PMID- 16464868
TI  - Co-expression of matriptase and N-acetylglucosaminyltransferase V in thyroid
      cancer tissues--its possible role in prolonged stability in vivo by aberrant
      glycosylation.
AB  - UDP-N-acetylglucosamine:alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase
      (GnT-V) catalyzes the formation of beta-1-6 GlcNAc branches on asparagine-linked
      oligosaccharides, which is directly linked to tumorigenesis. Our recent studies
      indicate that the secretion of matriptase from cancer cells is increased via the
      action of GnT-V, as evidenced by the fact that matriptase-bearing beta-1-6 GlcNAc
      branching is dramatically inhibited. In this study, we report on an investigation
      of the expression of GnT-V and matriptase in thyroid neoplasm tissues to
      determine the clinical significance on the co-expression of these two proteins in
      thyroid cancer. Although neither GnT-V nor matriptase was expressed in normal
      thyroid tissue, positive staining for matriptase and GnT-V was observed in 52/68
      and 66/68 cases of papillary carcinoma, 3/23 and 10/23 cases of follicular
      carcinoma, 5/13 and 9/13 cases of follicular adenoma, and 11/28 and 6/28 cases of
      anaplastic carcinoma, respectively. Immunohistochemistry, as well as western
      blotting, showed that the expression of matriptase paralleled the expression to
      GnT-V. However, the expression of matriptase mRNA was not correlated with its
      protein levels, suggesting that the enhancement in matriptase expression could be
      regulated by a posttranslational modification such as glycosylation through GnT-V
      mediated glycosylation. In papillary carcinoma, the levels of expression of both
      GnT-V and matriptase were significantly higher in tumors 1 cm or less in size
      (microcarcinoma) and in those without poorly differentiated lesions, and the two
      proteins were significantly correlated. In contrast, the prognosis of thyroid
      carcinoma after surgery was neither correlated with the expression GnT-V nor
      matriptase, because the levels of their expression were quite low in anaplastic
      (undifferentiated) carcinomas. These results suggest that prolonged stabilization
      of matriptase is stabilized by GnT-V-mediated glycosylation in vivo, thus
      extending its halftime and permitting it to play role in the early phases of
      papillary carcinoma, but not in its later phase progression.

PMID- 16464869
TI  - Incidence of GP-diagnosed respiratory tract infections according to age, gender
      and high-risk co-morbidity: the Second Dutch National Survey of General Practice.
AB  - BACKGROUND: Figures on GP-diagnosed respiratory tract infections (RTI) are
      outdated because of demographic changes and increase in co-morbid conditions,
      respiratory vaccination programmes and change in illness behaviour. OBJECTIVE: To
      determine the incidence of RTI in patients presenting to the GP according to age,
      gender and common high-risk co-morbidity in primary care. METHODS: In the Second
      Dutch National Survey of General Practice 90 computerized general practices with
      358,008 patients recorded all consecutive patient contact by use of the ICPC
      coding system in a year. Incidences were calculated using the mid-year population
      in the denominator and RTI episodes as the nominator. RESULTS: In all, 4.2% of
      the patient population were diagnosed with RTI with an incidence rate of 144 per
      1000 person-years. Upper RTI were more common in children of 0-4 years than in
      other year-cohorts [392 versus 80 per 1000; relative risk 4.9, 95% confidence
      interval (95% CI) 4.8-5.0]. An U-shape association was observed between age and
      lower RTI (78 and 70 per 1000 in children and persons aged 75 years or over,
      respectively, versus 23 per 1000 in other age-categories). Females had slightly
      higher incidence rates of URTI (relative risk 1.4, 95% CI 1.35-1.45) and similar
      rates for LRTI. Patients with chronic medical conditions as pulmonary and cardiac
      disease, and diabetes. DISCUSSION: A small proportion of the patient population
      present themselves to the GP with a RTI. RTI are more common among children,
      elderly persons and patients with pulmonary and cardiac disease, and diabetes of
      the ICPC coding system.

PMID- 16464870
TI  - European primary care surveillance networks: their structure and operation.
AB  - BACKGROUND: In many European countries, primary care surveillance networks play a
      role in public health surveillance. OBJECTIVES: To update an inventory of
      surveillance networks, to describe them and to report on their organization and
      function in a standardized way. To investigate whether and under what conditions
      their information can contribute to surveillance at a European level. METHODS:
      Surveillance networks were defined as 'A network of practices or community based
      primary care physicians who monitor one or more specific illness problems on a
      regular and continuing basis'. For the inventory questionnaires were sent out,
      followed by site visits to seven networks using a standardized audit checklist.
      RESULTS: We sent out 75 questionnaires and received 57 back (73% response rate),
      with 33 (58% of responders) fitting our selection criteria. National surveillance
      networks were identified in 11 countries. Many had an infectious disease
      surveillance component, particularly for influenza. Most were funded by the
      Ministry of Health, some by research funds. The median number of general
      practitioners was 120, comprising a stable group of general practitioners and
      covering a representative sample of the general population. The frequency of
      reporting varied from daily to annually, depending on the purpose of the network.
      CONCLUSIONS: A large number of primary care surveillance networks exist in
      Europe. Their value has been shown with the surveillance of influenza, but the
      challenge is now to extend their use to other diseases. When fulfilling identical
      minimal criteria they can provide comparable estimates of morbidity, ultimately
      leading to improved national and European surveillance.

PMID- 16464871
TI  - The use of an Internet-based Ask the Doctor Service involving family physicians:
      evaluation by a web survey.
AB  - BACKGROUND: Internet consultation without a previous relationship between the
      doctor and the enquirer seems to be increasing in popularity. However, little is
      known about the advantages, disadvantages or other differences compared with
      regular health care when using this kind of service. OBJECTIVE: To investigate
      how an Internet-based Ask the Doctor service out with any pre-existing doctor
      patient relationship was used and evaluated by the enquirers. METHODS: We
      recruited to a web-based survey users of the non-commercial Swedish Internet
      based Ask the Doctor service run by family physicians. The survey was conducted
      between November 2001 and January 2002. Questions included both multiple choice
      and free text formats, and the results were analysed quantitatively and
      qualitatively. RESULTS: The survey was completed by 1223 participants. It was
      mainly women who submitted questions to the service (29% men, 71% women) and also
      who participated in the survey (26% men, 74% women). Most participants (77%)
      wrote their question at home, and 80% asked on their own behalf. Almost half of
      the enquiries (45%) concerned a medical matter that had not been evaluated by a
      medical professional before. After reading the answer, 43% of the participants
      indicated that they would not pursue their question further having received
      sufficient information in the answer provided. The service was appreciated for
      its convenience and flexibility, but also for reasons to do with the mode of
      communication such as the ability to reflect on the written answer without having
      to hurry and to read it more than once. CONCLUSION: In the present study, we
      found that an Internet-based Ask the Doctor service run by family physicians on
      the whole was evaluated positively by the participants both in terms of the
      answers and the service. Internet-based consultation may act as a complement to
      regular health care. In future studies, the cost-effectiveness, patient security,
      responsibilities of the Internet doctor and the role of Ask the Doctor services
      compared with regular health care should be evaluated.

PMID- 16464872
TI  - Surgical repositioning of a developing maxillary permanent central incisor in a
      horizontal position: spontaneous eruption and root formation.
AB  - This report describes the surgical repositioning of a developing maxillary
      permanent central incisor in a horizontal position, followed by spontaneous
      eruption and root formation without orthodontic traction. Surgical exposure of
      the right central incisor was achieved. A 7-year-old boy referred for orthodontic
      consultation. Radiographic examination showed the crown of a maxillary right
      central incisor to be positioned horizontally with root formation at the initial
      stage. The surgically repositioned incisor (by a close-eruption surgical flap
      technique) spontaneously erupted into correct alignment after 2 years 3 months.
      The erupted incisor remained vital and responded normally to percussion, mobility
      and sensitivity testing. The soft tissue, periodontal attachment, gingival
      contour and probing depths were normal. Follow-up radiographs confirmed the
      continued development of the root, with revascularization of the pulp and a
      normal appearance of the periodontal space and lamina dura. There was, however,
      shorter root formation and a narrower root cavity compared with the contralateral
      incisor. As a result, no orthodontic traction and alignment were required. This
      method of surgical repositioning is a viable alternative to the traditional
      approach of extraction or surgical exposure followed by orthodontic traction for
      a developing maxillary permanent central incisor in a horizontal position.

PMID- 16464873
TI  - Sagittal airway dimensions following maxillary protraction: a pilot study.
AB  - The relationship between changes in the position of the maxillary structures
      caused by maxillary protraction therapy and airway dimensions have not been
      investigated as comprehensively as the accompanying skeletal changes. The purpose
      of this study was to examine the effects of rapid palatal expansion (RPE) used in
      conjunction with maxillary protraction headgear on the sagittal dimension of the
      airway. The treatment sample consisted of 19 Class III patients (12 girls, 7
      boys) with a mean age of 10.51 +/- 1.15 years, presenting with maxillary
      retrognathism. A cap splint type rapid palatal expander that had hooks between
      the upper lateral and canine teeth was used intraorally, and a Petit type
      facemask device extraorally, for an average of 6.78 +/- 0.93 months. Pre- and
      post-treatment cephalometric radiographs were evaluated. The results of the study
      revealed that point A moved anteriorly. The palatal plane showed a counter
      clockwise rotation matched by the clockwise rotation of the mandible and an
      accompanying decrease in SNB angle. The vertical parameters showed a
      statistically significant increase. The head was in a more extensive position in
      relation to the cervical vertebrae. The nasopharyngeal airway measurements (PNS
      ad1, PNS-ad2) showed an increase of 2.71 +/- 3.35 and 3.03 +/- 2.37 mm,
      respectively. These results demonstrated that limited maxillary widening together
      with protraction of the maxilla, improve nasopharyngeal but not oropharyngeal
      airway dimensions in the short term.

PMID- 16464874
TI  - Prediction of desiccation sensitivity in seeds of woody species: a probabilistic
      model based on two seed traits and 104 species.
AB  - BACKGROUND AND AIMS: Seed desiccation sensitivity limits the ex situ conservation
      of up to 47 % of plant species, dependent on habitat. Whilst desirable,
      empirically determining desiccation tolerance levels in seeds of all species is
      unrealistic. A probabilistic model for the rapid identification of woody species
      at high risk of displaying seed desiccation sensitivity is presented. METHODS:
      The model was developed using binary logistic regression on seed trait data [seed
      mass, moisture content, seed coat ratio (SCR) and rainfall in the month of seed
      dispersal] for 104 species from 37 families from a semi-deciduous tropical forest
      in Panama. KEY RESULTS: For the Panamanian species, only seed mass and SCR were
      significantly related to the response to desiccation, with the desiccation
      sensitive seeds being large and having a relatively low SCR (i.e. thin 'seed'
      coats). Application of this model to a further 38 species, of known seed storage
      behaviour, from two additional continents and differing vegetation types (dryland
      Africa and temperate Europe) correctly predicted the response to desiccation in
      all cases, and resolved conflicting published data for two species (Acer
      pseudoplatanus and Azadirachta indica). CONCLUSIONS: This model may have
      application as a decision-making tool in the handling of species of unknown seed
      storage behaviour in species from three disparate habitats.

PMID- 16464875
TI  - Cessation of tillering in spring wheat in relation to light interception and red
      : far-red ratio.
AB  - BACKGROUND AND AIMS: The production of axillary shoots (tillering) in spring
      wheat (Triticum aestivum) depends on intraspecific competition. The mechanisms
      that underlie this competition are complex, but light within the wheat canopy
      plays a key role. The main objectives of this paper are to analyse the effects of
      plant population density and shade on tillering dynamics of spring wheat, to
      assess the canopy conditions quantitatively at the time of tillering cessation,
      and to analyse the relationship between the tiller bud and the leaf on the same
      phytomer. METHODS: Spring wheat plants were grown at three plant population
      densities and under two light regimes (25 % and 100 % light). Tiller appearance,
      fraction of the light intercepted, and red : far-red ratio at soil level were
      recorded. On six sampling dates the growth status of axillary buds was analysed.
      KEY RESULTS: Tillering ceased earlier at high population densities and ceased
      earlier in the shade than in full sunlight. At cessation of tillering, both the
      fraction of light intercepted and the red : far-red ratio at soil level were
      similar in all treatments. Leaves on the same phytomer of buds that grew out
      showed more leaf mass per unit area than those on the same phytomer of buds that
      remained dormant. CONCLUSIONS: Tillering ceases at specific light conditions
      within the wheat canopy, independent of population density, and to a lesser
      extent independent of light intensity. It is suggested that cessation of
      tillering is induced when the fraction of PAR intercepted by the canopy exceeds a
      specific threshold (0.40-0.45) and red : far-red ratio drops below 0.35-0.40.

PMID- 16464876
TI  - Lignification and cell wall thickening in nodes of Phyllostachys
      viridiglaucescens and Phyllostachys nigra.
AB  - BACKGROUND AND AIMS: Bamboos are among the most important plants in the world.
      The anatomical structure and mechanical properties of the culm internode are well
      documented. Fewer details are available of the culm node. The aim of this study
      was a topochemical investigation on lignification and cell wall thickening in
      developing and maturing bamboo nodes. The deposition sequence and distribution of
      lignin structural units and cell wall thickening in different anatomical regions
      of the node of Phyllostachys viridiglaucescens and Phyllostachys nigra are
      discussed. METHODS: Cell wall thickening and lignification are investigated in
      the outer part of the nodal region and in the diaphragm of developing and
      maturing P. nigra culms and in maturing culms of P. viridiglaucescens of
      different age classes. The lignification during ageing was studied topochemically
      by means of cellular UV microspectrophotometry. A combination of light microscopy
      and image analysis techniques were used to measure cell wall thickness. KEY
      RESULTS: The fibre and parenchyma cell wall thickness does not significantly
      increase during ageing. In the diaphragm, the cell walls are thinner and the cell
      diameter is larger than in the outer part of the node. In shoots, the lignin
      content in the epidermis, hypodermis and in both fibre and parenchyma cells of
      the diaphragm is relatively low compared with older culms. The fibre and
      parenchyma cells of the diaphragm have higher values of p-coumaric and ferulic
      acids than fibre and parenchyma cells of the outer part of the node. CONCLUSIONS:
      It was hypothesized that the combination of more hydroxycinnamic acids and of
      thinner cell walls in combination with higher cell diameters (lower density and
      lower stiffness) in the diaphragm than in the outer part of the node may play an
      important role in the biomechanical function of the node by acting as a spring
      like joint to support the culm by bending forces.

PMID- 16464877
TI  - Silica deposition in abaxial epidermis before the opening of leaf blades of
      Pleioblastus chino (Poaceae, Bambusoideae).
AB  - BACKGROUND AND AIMS Silica deposition is one of the important characteristics of
      the family Poaceae. The distribution, deposition process and physiology of silica
      in this family have been extensively investigated. Bamboos among members of
      Poaceae have leaves with a fairly long life span, and the leaves continuously
      accumulate silica in their tissues throughout their life, not only during the
      course of leaf opening, but also after opening. It has been revealed that the
      silica deposition process in relation to ageing of the bamboo leaf after opening
      differed depending on the cell types comprising the tissues. However, silica
      deposition has never been examined during the development and maturation periods
      of bamboo leaves. Hence, to clarify the silica deposition process in a
      developmental stage of the bamboo leaf, distribution of silica was observed in
      the abaxial epidermis before the opening of the leaf blades of Pleioblastus
      chino. METHODS: Abaxial epidermal tissues of leaves were examined using a
      scanning electron microscope equipped with an energy dispersive X-ray
      microanalyser. KEY RESULTS: Among seven cell types comprising the abaxial
      epidermis, three types of cells, guard cells, prickle hairs and silica cells,
      deposited silica conspicuously, and another four types, cork cells, long cells,
      micro hairs and subsidiary cells, deposited only a little silica. Among the
      former group of cell types, silica cells and guard cells deposited silica over
      their entire surfaces, while prickle hairs deposited silica only in the point
      tips. Silica deposition was detected firstly in prickle hairs, and then in silica
      cells and guard cells. Only silica cells were assumed to deposit silica
      conspicuously before leaf opening but not conspicuously after opening.
      CONCLUSIONS: Cell types in leaf epidermis of bamboo are classified into three
      groups according to the silica deposition pattern. Silica deposition in silica
      cells may be positive as a part of the physiological activities of leaves.

PMID- 16464878
TI  - Effects of preconditioning and temperature during germination of 73 natural
      accessions of Arabidopsis thaliana.
AB  - BACKGROUND AND AIMS: Germination and establishment of seeds are complex traits
      affected by a wide range of internal and external influences. The effects of
      parental temperature preconditioning and temperature during germination on
      germination and establishment of Arabidopsis thaliana were examined. METHODS:
      Seeds from parental plants grown at 14 and at 22 degrees C were screened for
      germination (protrusion of radicle) and establishment (greening of cotyledons) at
      three different temperatures (10, 18 and 26 degrees C). Seventy-three accessions
      from across the entire distribution range of A. thaliana were included. KEY
      RESULTS: Multifactorial analyses of variances revealed significant differences in
      the effects of genotypes, preconditioning, temperature treatment, and their
      interactions on duration of germination and establishment. Reaction norms showed
      an enormous range of plasticity among the preconditioning and different
      germination temperatures. Correlations of percentage total germination and
      establishment after 38 d with the geographical origin of accessions were only
      significant for 14 degrees C preconditioning but not for 22 degrees C
      preconditioning. Correlations with temperature and precipitation on the origin of
      the accessions were mainly found at the lower germination temperatures (10 and 18
      degrees C) and were absent at higher germination temperatures (26 degrees C).
      CONCLUSIONS: Overall, the data show huge variation of germination and
      establishment among natural accessions of A. thaliana and might serve as a
      valuable source for further germination and plasticity studies.

PMID- 16464879
TI  - Leaf vascular systems in C(3) and C(4) grasses: a two-dimensional analysis.
AB  - BACKGROUND AND AIMS: It is well documented that C(4) grasses have a shorter
      distance between longitudinal veins in the leaves than C(3) grasses. In grass
      leaves, however, veins with different structures and functions are
      differentiated: large longitudinal veins, small longitudinal veins and transverse
      veins. Thus, the densities of the three types of vein in leaves of C(3) and C(4)
      grasses were investigated from a two-dimensional perspective. METHODS: Vein
      densities in cleared leaves of 15 C(3) and 26 C(4) grasses representing different
      taxonomic groups and photosynthetic subtypes were analysed. KEY RESULTS: The C(4)
      grasses had denser transverse veins and denser small longitudinal veins than the
      C(3) grasses (1.9 and 2.1 times in interveinal distance), but there was no
      significant difference in large longitudinal veins. The total length of the three
      vein types per unit area in the C(4) grasses was 2.1 times that in the C(3)
      grasses. The ratio of transverse vein length to total vein length was 14.3 % in
      C(3) grasses and 9.9 % in C(4) grasses. The C(3) grasses generally had greater
      species variation in the vascular distances than the C(4) grasses. The bambusoid
      and panicoid C(3) grasses tended to have a denser vascular system than the
      festucoid C(3) grasses. There were no significant differences in the interveinal
      distances of the three vein types between C(4) subtypes, although the NADP-malic
      enzyme grasses tended to have a shorter distance between small longitudinal veins
      than the NAD-malic enzyme and phosphoenolpyruvate carboxykinase grasses.
      CONCLUSIONS: It seems that C(4) grasses have structurally a superior
      photosynthate translocation and water distribution system by developing denser
      networks of small longitudinal and transverse veins, while keeping a constant
      density of large longitudinal veins. The bambusoid and panicoid C(3) grasses have
      a vascular system that is more similar to that in C(4) grasses than to that in
      the festucoid C(3) grasses.

PMID- 16464880
TI  - Effect of thawing time, cooling rate and boron nutrition on freezing point of the
      primordial shoot in norway spruce buds.
AB  - BACKGROUND: Effects of cooling rates on bud frost hardiness have been studied but
      there is little information on bud responses to thawing. Since the cell wall pore
      size has been found to increase with boron (B) deficiency, B deficiency may
      affect the supercooling ability of buds in winter. METHODS: The effects of
      duration of thawing time and rate of cooling on bud frost hardiness of Norway
      spruce (Picea abies) were studied in a B fertilization trial in February 2003 and
      March 2005. Frost hardiness of apical buds was determined by differential thermal
      analysis (DTA) and visual scoring of damage. KEY RESULTS: In 2003, the freezing
      point of primordial shoots of buds (T(f)), i.e. the low-temperature exotherm
      (LTE), was, on average, -39 degrees C when buds were thawed for less than 3 h and
      the T(f) increased to -21 degrees C after 18 h of thawing. During the first 4 h
      of thawing, the rate of dehardening was 6 degrees C h(-1). In 2005, buds
      dehardened linearly from -39 degrees C to -35 degrees C at a rate of 0.7 degrees
      C h(-1). In 2003, different cooling rates of 1-5 degrees C h(-1) had a minor
      effect on T(f) but in 2005 with slow cooling rates T(f) decreased. In both
      samplings, at cooling rates of 2 and 1 degrees C h(-1), T(f) was slightly higher
      in B-fertilized than in non-fertilized trees. By contrast, at very short thawing
      times in 2003, T(f) was somewhat lower in B-fertilized trees. CONCLUSIONS: There
      was little evidence of reduced frost hardiness in trees with low B status. This
      study showed that buds deharden rapidly when exposed to above-freezing
      temperatures in winter, but if cooled again they reharden more slowly. According
      to this study, rapid dehardening of buds has to be taken into account in
      assessments of frost hardiness.

PMID- 16464882
TI  - Uraemia, psychosis, young patient: an uncommon link. Urinary tract and miliary
      tuberculosis.

PMID- 16464883
TI  - Transhepatic venous access as an alternative for Tesio catheter in the case of a
      patient on haemodialysis with antiphospholipid syndrome.

PMID- 16464884
TI  - Inflammation and hypertension: the search for a link.

PMID- 16464881
TI  - Regulation of sulfate assimilation in Arabidopsis and beyond.
AB  - BACKGROUND AND AIMS: Sulfate assimilation is a pathway used by prokaryotes, fungi
      and photosynthetic organisms to convert inorganic sulfate to sulfide, which is
      further incorporated into carbon skeletons of amino acids to form cysteine or
      homocysteine. The pathway is highly regulated in a demand-driven manner; however,
      this regulation is not necessarily identical in various plant species. Therefore,
      our knowledge of the regulation of sulfate assimilation is reviewed here in
      detail with emphasis on different plant species. SCOPE: Although demand-driven
      control plays an essential role in regulation of sulfate assimilation in all
      plants, the molecular mechanisms of the regulation and the effects of various
      treatments on the individual enzymes and metabolites are often different. This
      review summarizes (1) the molecular regulation of sulfate assimilation in
      Arabidopsis thaliana, especially recent data derived from platform technologies
      and functional genomics, (2) the co-ordination of sulfate, nitrate and carbon
      assimilations in Lemna minor, (3) the role of sulfate assimilation and
      glutathione in plant-Rhizobia symbiosis, (4) the cell-specific distribution of
      sulfate reduction and glutathione synthesis in C(4) plants, (5) the regulation of
      glutathione biosynthesis in poplar, (6) the knock-out of the adenosine
      5'phosphosulfate reductase gene in Physcomitrella patens and identification of 3'
      phosphoadenosyl 5'-phosphosulfate reductase in plants, and (7) the sulfur sensing
      mechanism in green algae. CONCLUSIONS: As the molecular mechanisms of regulation
      of the sulfate assimilation pathway are not known, the role of Arabidopsis as a
      model plant will be further strengthened. However, this review demonstrates that
      investigations of other plant species will still be necessary to address specific
      questions of regulation of sulfur nutrition.

PMID- 16464885
TI  - Application of NKF-K/DOQI Clinical Practice Guidelines for Bone Metabolism and
      Disease: changes of clinical practices and their effects on outcomes and quality
      standards in three haemodialysis units.
AB  - BACKGROUND: The K/DOQI Clinical Practice Guidelines for Bone Metabolism and
      Disease in Chronic Kidney Disease was published in October 2003. The objective of
      this study was to analyse the effect of the application of those guidelines on
      clinical practices and on the achievement of bone disease targets and quality
      standards. METHODS: We included in the study 342 patients dialysed in our three
      HD units during 2003 and 2004. Starting October 2003, the K-DOQI recommendations
      were introduced into practice. Parathyroid hormone (PTH) was measured every 3
      months and the serum Ca and P levels, monthly. In patients whose medications were
      modified, PTH was measured monthly and Ca and P levels, weekly or biweekly.
      RESULTS: The following are the main findings for 2004 (post-K/DOQI): an increased
      use of dialysates with a Ca concentration of 2.5 mEq/l (27.2-50.9%, P<0.001) and
      a reduced use of a dialysate calcium of 3.0 mEq/l (44.6-39.6%, P: NS) and 3.5
      mEq/l (28-9.4%, P<0.001); a reduced use of calcium-based phosphate binders (891.9
      565.5 mg Ca/day, P<0.001) and increased use of sevelamer hydrochloride (800 mg)
      (from 4.86 to 7.51 mg, tablets/day, P<0.001) lower serum Ca levels (9.7-9.4
      mg/dl, P<0.01), and higher intact PTH levels (201.4-311.8 pg/ml, P<0.001),
      without changes in serum P levels; an increased proportion of patients with serum
      Ca levels within the K/DOQI target range (38.7-46.6%, P<0.01), resulting mainly
      from the reduced percentage of patients with hypercalcaemia (55-44.4%, P<0.01); a
      decreased proportion of patients with PTH<150 pg/ml (53.8-31.4%, P<0.001) but an
      increased proportion of patients with PTH>300 pg/ml, with no change in the
      proportion of patients with PTHs within the K/DOQI target range. Phosphorus
      levels and targets did not show significant differences between 2003 and 2004
      (56.9-56.2%, P: NS). CONCLUSIONS: The only way to ensure that K/DOQI guidelines
      actually improve medical outcomes is to emphasize implementation strategies and
      also the scientific evaluation of their effectiveness in clinical settings. In
      spite of the application of the K-DOQI recommendations, a large proportion of our
      patients stayed outside the proposed targets, which points to the need for more
      effective therapeutic options.

PMID- 16464886
TI  - Myeloperoxidase up-regulation during haemodialysis: is heparin the missing link?

PMID- 16464887
TI  - On-line haemodiafiltration with and without acetate.
AB  - BACKGROUND: In patients on on-line convective treatments, given the considerable
      quantity of dialysis fluid re-infused, the small amount of acetate present in
      bicarbonate dialysis fluid as a pH stabilizing factor may allow a significant
      transfer of that anion to the patient, possibly inducing cytokine activation.
      METHODS: To verify this hypothesis, we performed on-line haemodiafiltration (OL
      HDF) with (3 mmol/l) and without acetate in dialysis fluid in a cross-over
      randomized order on 12 prevalent patients. RESULTS: In comparison with the pre
      treatment values, plasma acetate levels were unchanged during and after acetate
      free OL-HDF, while they were 5-6 times higher in the course of OL-HDF containing
      acetate in dialysis fluid; plasma acetate levels returned to basal values 2 h
      after the end of the procedure. The total increase of bases in the patient
      attributable to acetate was 36%. Plasma bicarbonate values at the end of
      treatment were significantly lower in treatments without acetate, as compared to
      those with acetate. Interleukin-6 plasma levels were super-imposable at the
      beginning and in the course of the two methods compared, but there was a tendency
      towards a greater increase at an interval of 2 h following OL-HDF with acetate.
      CONCLUSIONS: Our preliminary results confirm the assumption that body gain of
      acetate is particularly high in convective treatments, while acetate-free OL-HDF
      slows down acetate burden. Clinical advantages due to these effects should be
      evaluated in properly designed prospective studies.

PMID- 16464888
TI  - HIV entry inhibitors: mechanisms of action and resistance pathways.
AB  - Entry inhibitors represent a new generation of antivirals for the treatment of
      HIV infection. Several compounds which block the attachment of HIV gp120 to
      either the CD4 T cell receptor or the CCR5/CXCR4 co-receptors are currently in
      clinical development. Most of these compounds have different molecular structures
      and specific mechanisms of action. These agents are eagerly awaited by a growing
      number of patients carrying viruses resistant viruses to many of the current
      available reverse transcriptase and protease inhibitors. For enfuvirtide, the
      first and, so far, only entry inhibitor approved for clinical use, the main
      mechanism of resistance is the selection of changes within a 10 amino acid
      segment encompassing residues 36-45 within the HR1 region of gp41. For other
      entry inhibitors, multiple changes in different gp120 domains (V1, V2, V3, C2 and
      C4) have been associated with loss of susceptibility to these agents, although in
      most cases with limited cross-resistance.

PMID- 16464889
TI  - Emergence of a 23S rRNA mutation in Mycoplasma hominis associated with a loss of
      the intrinsic resistance to erythromycin and azithromycin.
AB  - OBJECTIVES: Mycoplasma hominis is intrinsically resistant to 14- and 15-membered
      macrolides and to the ketolide telithromycin but is susceptible to josamycin, a
      16-membered macrolide, and lincosamides. The aim of our study was to investigate
      the in vitro development of macrolide resistance in M. hominis and to study the
      impact of ribosomal mutations on MICs of various macrolides and related
      antibiotics. METHODS: Selection of macrolide-resistant mutants was performed by
      serial passages of M. hominis PG21 in broth medium containing subinhibitory
      concentrations of clindamycin, pristinamycin, quinupristin/dalfopristin and
      telithromycin. Stepwise selection of josamycin-resistant mutants was performed
      onto agar medium containing increasing inhibitory concentrations of josamycin.
      Resistant mutants were characterized by PCR amplification and DNA sequencing of
      23S rRNA, L4 and L22 ribosomal protein genes. RESULTS: Various mutations in
      domain II or V of 23S rRNA were selected in the presence of each selector
      antibiotic and were associated with several resistance phenotypes. Josamycin was
      the sole antibiotic that selected for single amino acid changes in ribosomal
      proteins L4 and L22. Unexpectedly, the C2611U transition selected in the presence
      of clindamycin and the quinupristin/dalfopristin combination was associated with
      decreased MICs of erythromycin, azithromycin and telithromycin, leading to a loss
      of the intrinsic resistance of M. hominis to erythromycin and azithromycin.
      CONCLUSIONS: Ribosomal mutations were associated with resistance to macrolides
      and related antibiotics in M. hominis. Some mutants showed a loss of the
      intrinsic resistance to erythromycin and azithromycin.

PMID- 16464890
TI  - The role of horizontal gene transfer in the spread of trimethoprim
      sulfamethoxazole resistance among uropathogenic Escherichia coli in Europe and
      Canada.
AB  - OBJECTIVES: To describe the distribution of trimethoprim-sulfamethoxazole
      resistance genes and the role of horizontal gene transfer and clonal expansion in
      recent increases of antibiotic resistance rates among uropathogenic Escherichia
      coli in Europe and Canada. METHODS: We identified antibiotic resistance alleles
      sul1, sul2, sul3 and dfr along with type 1 and type 2 integrons among 350
      uropathogenic E. coli isolates from a cross-sectional study of acute,
      uncomplicated, community-acquired urinary tract infections in 16 western European
      countries and Canada (ECOSENS). RESULTS: Trimethoprim resistance gene
      distributions showed no regional dependency (P = 0.84). The most common
      trimethoprim resistance gene was dfrA1, which occurred in 37.9% of dfr containing
      isolates. Similarly, the sulfamethoxazole resistance gene distributions did not
      vary significantly by region (P = 0.20). sul2, the most common sulfamethoxazole
      resistance gene, was found in 77.9% of sulfamethoxazole-resistant isolates. The
      distribution of type 1 and type 2 integrons varied slightly by region (P = 0.04)
      with type 1 integrons being the more common (85.9%). We observed 34 combinations
      of the sul genes, dfr genes and integron types; the most common combinations were
      broadly disseminated across every region examined. CONCLUSIONS: Horizontal gene
      transfer plays a larger role than clonal expansion in the increase of
      trimethoprim-sulfamethoxazole resistance levels in Europe and Canada.

PMID- 16464891
TI  - Susceptibility to protease inhibitors in HIV-2 primary isolates from patients
      failing antiretroviral therapy.
AB  - BACKGROUND: Current protease inhibitors (PIs) are designed against HIV-1, and
      information on their performance against HIV-2 clinical isolates is scarce.
      METHODS: Genetic and phenotypic analyses using all available PIs were performed
      in five HIV-2 primary isolates from two patients on regular follow-up who failed
      PI-HAART. RESULTS: HIV-2 proteases before therapy showed amino acids associated
      with resistance in HIV-1 (pro10V, pro32I, pro36I, pro46I, pro47V, pro71V and
      pro73A). Phenotypic results showed that indinavir, saquinavir, lopinavir and
      tipranavir had full activity against wild-type HIV-2. However, a susceptibility
      reduction was noticed for nelfinavir (6.6-fold) and amprenavir (31-fold). During
      therapy with lopinavir, one patient developed proV47A, which translated into high
      level resistance (13.4- to 41-fold) to indinavir, lopinavir and amprenavir, and
      hypersusceptibility to saquinavir. All isolates from the other patient had
      multiple mutations after several PIs failed (proV10I, proV33L, proI54M, proV71I
      and proI82F). The acquisition of mutations 54M and 82F along with naturally
      occurring changes resulted in multi-PI-resistant viruses (33- to >1000-fold), and
      only saquinavir retained full activity. CONCLUSIONS: Naturally occurring
      secondary mutations or polymorphisms in the HIV-2 protease may decrease the
      activity of nelfinavir and amprenavir. Moreover, upon selection of primary
      resistance mutations, pre-existing secondary changes might play an important role
      in the acquisition of a multi-PI resistance phenotype in HIV-2.

PMID- 16464892
TI  - Effects of prolonged vancomycin administration on methicillin-resistant
      Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia.
AB  - OBJECTIVES: To evaluate microbiological properties of methicillin-resistant
      Staphylococcus aureus (MRSA) during prolonged vancomycin therapy. METHODS: We
      evaluated vancomycin susceptibility and heteroresistance, accessory gene
      regulator (agr) function, autolysis, biofilm production and in vitro vancomycin
      killing in serial MRSA bloodstream isolates obtained over a 30 month period from
      a patient with a chronic endovascular infection. RESULTS: Despite the fact that
      the MRSA in this patient had the same genetic background as other clinical
      glycopeptide intermediate-resistant S. aureus (GISA) isolates, vancomycin
      administered for 9 months, maintaining serum concentrations >10 mg/L, did not
      select for GISA. Minimal changes in vancomycin susceptibility were detected using
      agar dilution and population analysis methods. We noted increases in delta
      haemolysin production, autolysis and the bactericidal effects of vancomycin in
      vitro against the MRSA obtained after prolonged vancomycin suppressive therapy
      was discontinued. CONCLUSIONS: Despite the lack of development of detectable
      resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop
      vancomycin tolerance and decreased autolysis. In addition, suppression of agr
      function appears to end after vancomycin is stopped. Whether these changes are
      prerequisites for attenuated vancomycin efficacy and the development of
      glycopeptide resistance warrants further study. The development of vancomycin
      resistance may be more difficult under conditions where vancomycin serum
      concentrations are maintained >10 mg/L.

PMID- 16464893
TI  - Progressive loss of echinocandin activity following prolonged use for treatment
      of Candida albicans oesophagitis.
AB  - OBJECTIVES: To illustrate the progressive loss of cross-echinocandin activity on
      Candida albicans isolates with strong clonal homology from a patient with
      advanced HIV infection and chronic oesophagitis progressively resistant to
      uninterrupted micafungin treatment. METHODS: Antifungal susceptibility profiles
      for different antifungal agents were determined against serial C. albicans
      isolates retrieved before and during therapy. Multilocus sequencing typing (MLST)
      was performed on each of the isolates. FKS1 mutations conferring reduced
      susceptibility to echinocandin drugs were determined by DNA sequence analysis.
      RESULTS: Four C. albicans isolates showing identical allelic homology were
      retrieved from the patient at the initiation and during therapy with micafungin.
      The progressive lack of clinical response to micafungin therapy was associated
      with increased MICs of all three echinocandin drugs (caspofungin, micafungin and
      anidulafungin) in association with the acquisition of mutations in the FKS1 gene.
      CONCLUSIONS: This report documents for the first time a progressive loss of
      activity of all three echinocandin drugs against clonally related C. albicans
      isolates following long-term clinical exposure to this new class of antifungal
      agents.

PMID- 16464894
TI  - Erythrosine is a potential photosensitizer for the photodynamic therapy of oral
      plaque biofilms.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical plaque
      disclosing agent erythrosine as a photosensitizer in the photodynamic killing of
      the oral bacterium Streptococcus mutans grown as a biofilm. METHODS: S. mutans
      biofilms of 200 microm thickness were grown in a constant-depth film fermenter.
      In addition to determining localization of the photosensitizer within biofilms
      using confocal laser scanning microscopy (CLSM), we compared the bacterial
      killing efficacy of erythrosine with that of two well-characterized
      photosensitizers, methylene blue (MB) and photofrin. Incubations were carried out
      with each photosensitizer (22 microM), and irradiation was for 15 min using a 400
      W white light source. RESULTS: The CLSM results showed that erythrosine is taken
      up into S. mutans biofilms, where it is associated with the biomass of the
      biofilm rather than the fluid-filled channels and voids. Comparison of the cell
      killing efficacy of erythrosine in S. mutans biofilms of different ages showed
      that erythrosine was 1-2 log(10) more effective at killing biofilm bacteria than
      photofrin and 0.5-1 log(10) more effective than MB. The results were
      statistically significant (P < 0.01). Photodynamic therapy (PDT) with all three
      photosensitizers was increasingly effective as biofilm age increased, suggesting
      that temporal changes in biofilm architecture and composition affect
      susceptibility to PDT. CONCLUSIONS: PDT using erythrosine as photosensitizer
      shows excellent potential as a treatment for oral plaque biofilms.

PMID- 16464895
TI  - Caspofungin: antifungal activity in vitro, pharmacokinetics, and effects on
      fungal load and animal survival in neutropenic rats with invasive pulmonary
      aspergillosis.
AB  - OBJECTIVES: Evaluation of the potential of caspofungin, in relation to
      pharmacokinetics, in order to optimize its use in the treatment of filamentous
      fungal infections. METHODS: The in vitro antifungal activity, pharmacokinetics
      and therapeutic efficacy of caspofungin versus amphotericin B was investigated in
      vitro as well as in a model of aerogenic Aspergillus fumigatus infection in
      neutropenic rats, using rat survival and decrease in fungal burden as parameters
      for therapeutic efficacy. RESULTS: In contrast to amphotericin B, caspofungin
      shows a concentration-dependent gradual decrease in fungal growth in vitro, which
      makes it difficult to perform visual readings of antifungal activity (CLSI
      guidelines). The quantitative XTT [2,3-bis(2-methoxy-4-nitro-5-[(sulphenylamino)
      carbonyl]-2H-tetrazolium-hydroxide] assay measuring a decrease in fungal
      metabolic activity seems more appropriate for caspofungin susceptibility testing.
      Using this assay, in vitro caspofungin was 4-fold less active than amphotericin
      B. In the infection model, therapy was started 16 h after fungal inoculation, and
      continued once daily for 10 days. Caspofungin was administered intraperitoneally
      at 1, 2, 3 or 4 mg/kg/day (CAS 1, 2, 3 or 4), amphotericin B at 1 mg/kg/day (AMB
      1). Treatment with CAS 1 or AMB 1 provided modest prolongation of animal
      survival. The combination of caspofungin and amphotericin B did not show additive
      effects. Increasing the dosage of caspofungin to 2, 3 or 4 mg/kg/day resulted in
      a dose-dependent significant increase in efficacy. There was 100% survival among
      rats in the CAS 4 group, which was correlated with a significant decrease in
      fungal burden, based on the concentration of A. fumigatus galactomannan in serum
      and lung tissue and quantification of A. fumigatus DNA in lung tissue.
      Pharmacokinetic analysis suggested that the CAS 4 dose in rats produced drug
      exposure comparable to the human situation, visualized by similar 24 h AUC and
      trough concentrations. CONCLUSIONS: The therapeutic efficacy of caspofungin is
      superior to amphotericin B, which seemed to be discrepant with their in vitro
      antifungal activity.

PMID- 16464896
TI  - Measurement of ampicillin, vancomycin, linezolid and gentamicin activity against
      enterococcal biofilms.
AB  - BACKGROUND: Enterococci frequently cause biofilm infections but susceptibility of
      clinical isolates growing in biofilms has not been investigated. The minimum
      biofilm eradicating concentration (MBEC) has been suggested as a guide to
      treatment of biofilm infections. We measured an alternative endpoint, the minimum
      biofilm inhibitory concentration (MBIC) and compared the results with MIC and
      MBC. OBJECTIVES: To compare the MIC, MBC and MBIC of ampicillin, vancomycin and
      linezolid against enterococcal biofilms, to assess the impact of additional
      gentamicin and correlate findings with clinical outcome. METHODS: MIC and MBC
      were measured using standard techniques. MBICs were measured using a modification
      of the Calgary biofilm device method. Fifty-eight enterococcal isolates from
      episodes of intravascular catheter-related bloodstream infection were tested.
      RESULTS: Tolerance to ampicillin, vancomycin and linezolid was seen in 93%, 100%
      and 93% of isolates, respectively. MIC(90)s of ampicillin, vancomycin and
      linezolid were all 4 mg/L for Enterococcus faecalis isolates. MBC(90)s of
      ampicillin, vancomycin and linezolid for E. faecalis isolates were 1024, >128 and
      2048 mg/L, respectively. MBIC(90)s of ampicillin, vancomycin and linezolid for E.
      faecalis isolates were 8192, 4096 and 4096 mg/L, respectively. Results for
      Enterococcus faecium were similar for vancomycin and linezolid but this species
      was generally more resistant to ampicillin. Adding 10 mg/L gentamicin had a
      variable effect on MIC, MBC or MBIC, which was not predictable by gentamicin
      susceptibility on disc testing. CONCLUSIONS: Very high concentrations of
      ampicillin, vancomycin and linezolid are required to inhibit enterococcal
      biofilms in vitro. Combining these agents with gentamicin significantly reduced
      MIC, MBC and MBIC against only a proportion of enterococcal isolates. No
      correlation between MBIC and outcome was found.

PMID- 16464897
TI  - Antimicrobial susceptibility of Bartonella henselae using Etest methodology.
AB  - OBJECTIVES: Bartonella henselae is a fastidious slow growing pathogen which is
      seldom cultured in the laboratory. Previous descriptions of antimicrobial
      susceptibility have been largely limited to feline isolates and/or laboratory
      reference strains, with no accounting for genotypic or phenotypic diversity.
      METHODS: An optimal method of antimicrobial susceptibility testing by Etest was
      established to compare the antimicrobial susceptibilities of 12 different
      isolates of B. henselae, 5 human and 7 feline, which have previously been well
      characterized by 16S rRNA sequencing, multi-locus sequence typing (MLST), phase
      variation and passage number. RESULTS: No difference in susceptibility could be
      attributed to differences in genotype, source of the isolate or passage number.
      Where comparisons were drawn with previously published results, these were found
      to be concordant. CONCLUSIONS: We conclude that antibiotic susceptibility can be
      determined by a simple Etest method for B. henselae isolates. This method is
      reproducible among diverse strains, and is sufficiently predictable that
      generalizations can be confidently made about optimal antibiotic choices.

PMID- 16464898
TI  - Adult onset subacute sclerosing panencephalitis: clinical profile of 39 patients
      from a tertiary care centre.
AB  - Clinical and laboratory characteristics of 39 patients with adult onset subacute
      sclerosing panencephalitis (SSPE) are described and compared to those of juvenile
      onset patients regarding preceding measles, age at onset, gender, interval
      between onset and diagnosis, clinical profile, and course during follow up.
      Diagnosis was based on clinical and electroencephalographic findings and raised
      anti-measles antibody titres in cerebrospinal fluid. Mean age at SSPE symptom
      onset was 20.9+/-4.9 years and mean interval from onset to diagnosis was 6.3+/
      9.6 months. Referral diagnosis was accurate in only 12 patients. Presenting
      symptoms included myoclonus, behavioural changes, seizures, and cognitive,
      visual, and extrapyramidal disturbance. All patients received symptomatic
      therapy; 19 also received disease modifying agents. Five of seven pregnant women
      had successful deliveries. The follow-up period varied widely (maximum 60 months,
      median 9 months). The profile of adult onset SSPE did not differ from the rest of
      the cohort, except for a longer interval between measles infection and symptom
      onset (p<0.0001). SSPE in adults poses diagnostic challenges for clinicians. A
      high index of suspicion and appropriate investigations are necessary for early
      diagnosis and counselling.

PMID- 16464899
TI  - An epidemiological study of head injuries in a UK population attending an
      emergency department.
AB  - We aimed to identify the attendance rate for all head injuries, and for moderate
      to severe head injury (MSHI), in an emergency department (ED), and related risk
      factors for MSHI, including age, sex, area of residence, and socioeconomic status
      (SES). This was a retrospective descriptive epidemiological study of an ED
      database of head injury attendances over 6 years, carried out in an ED that
      serves both urban and mixed rural and urban areas, with a wide socioeconomic
      range, and a total population of 344,600. The main outcome measure was rates of
      attendance for head injury. Head injury presentations accounted for 3.4% of all
      attendances per year. An overall rate of 453 per 100,000 was found for all head
      injuries, of which 40 per 100,000 were moderate to severe (10.9%). Urban
      residents had significantly greater risk of presenting with MSHI compared with
      residents of mixed/rural areas. Males were more at risk than females, and
      children and adolescents had higher risk of MSHI. A high attendance rate of MSHI
      was found in the <5 year old age group in urban areas for both sexes. A gradient,
      with higher attendance in groups with lower SES, was observed for children in
      urban areas, while the gradient was reversed in mixed/rural areas. Head injuries
      are a relatively common cause of attendance at ED. There is significant variation
      in attendance with MSHI with regard to sex, age, socioeconomic factors, and type
      of area of residence. The planning and delivery of preventative and management
      services may be improved by such analyses.

PMID- 16464900
TI  - Prevalence and characteristics of peripheral neuropathy in hepatitis C virus
      population.
AB  - OBJECTIVE: To assess the prevalence of peripheral neuropathy (PN) and its
      correlation with cryoglobulinemia (CG) in an unselected, untreated referral
      hepatitis C virus (HCV) population. PATIENTS AND METHODS: Two hundred and thirty
      four patients (120 women and 114 men) with untreated HCV infection were
      consecutively enrolled by seven Italian centres. Clinical neuropathy was
      diagnosed when symptoms and signs of peripheral sensory or motor involvement were
      present. Median, ulnar, peroneal, and sural nerves were explored in all patients
      and distal symmetric polyneuropathy was diagnosed when all explored nerves or
      both lower limb nerves were affected. Mononeuropathy and mononeuropathy multiplex
      were diagnosed when one nerve or two non-contiguous nerves with asymmetrical
      distribution were affected. Screening for CG was done in 191 unselected patients.
      RESULTS: Clinical signs of PN were observed in 25 of the 234 patients (10.6%).
      Electrophysiological PN was found in 36 (15.3%). CG was present in 56/191
      patients (29.3%). The prevalence of CG increased significantly with age (p<0.001)
      and disease duration (p<0.05). PN was present in 12/56 (21%) patients with CG and
      18/135 (13%) without CG (p=NS). PN increased significantly with age (p<0.001) and
      logistic regression analysis confirmed age as the only independent predictor of
      PN (OR 1.10 for each year; 95% CI 1.04 to 1.15; p<0.001). CONCLUSIONS:
      Electrophysiological examination detected subclinical neuropathy in 11 patients
      (4.7%). Statistical analysis showed that CG was not a risk factor for PN whereas
      PN prevalence increased significantly with age.

PMID- 16464901
TI  - Depersonalisation/derealisation symptoms in vestibular disease.
AB  - BACKGROUND: Depersonalisation is a subjective experience of unreality and
      detachment from the self often accompanied by derealisation; the experience of
      the external world appearing to be strange or unreal. Feelings of unreality can
      be evoked by disorienting vestibular stimulation. OBJECTIVE: To identify the
      prevalence of depersonalisation/derealisation symptoms in patients with
      peripheral vestibular disease and experimentally to induce these symptoms by
      vestibular stimulation. METHODS: 121 healthy subjects and 50 patients with
      peripheral vestibular disease participated in the study. For comparison with the
      patients a subgroup of 50 age matched healthy subjects was delineated. All
      completed (1) an in-house health screening questionnaire; (2) the General Health
      Questionnaire (GHQ-12); (3) the 28-item depersonalisation/derealisation inventory
      of Cox and Swinson (2002). Experimental verification of "vestibular induced"
      depersonalisation/derealisation was assessed in 20 patients and 20 controls
      during caloric irrigation of the labyrinths. RESULTS: The frequency and severity
      of symptoms in vestibular patients was significantly higher than in controls. In
      controls the most common experiences were of "deja vu" and "difficulty in
      concentrating/attending". In contrast, apart from dizziness, patients most
      frequently reported derealisation symptoms of "feel as if walking on shifting
      ground", "body feels strange/not being in control of self", and "feel 'spacey' or
      'spaced out'". Items permitted discrimination between healthy subjects and
      vestibular patients in 92% of the cases. Apart from dizziness, caloric
      stimulation induced depersonalisation/derealisation symptoms which healthy
      subjects denied ever experiencing before, while patients reported that the
      symptoms were similar to those encountered during their disease. CONCLUSIONS:
      Depersonalisation/derealisation symptoms are both different in quality and more
      frequent under conditions of non-physiological vestibular stimulation. In
      vestibular disease, frequent experiences of derealisation may occur because
      distorted vestibular signals mismatch with the other sensory input to create an
      incoherent frame of spatial reference which makes the patient feel he or she is
      detached or separated from the world.

PMID- 16464902
TI  - Making sense of medical technology.
AB  - In seeking to explain contradictory reports that increased medical spending is
      both valuable and wasteful, Jonathan Skinner and colleagues rightly emphasize
      differences in regional practice patterns in response to constraints. However, it
      is more accurate to view the situation not as a choice between valuable but
      inexpensive care and more costly care with worse outcomes-as Skinner and
      colleagues theorize-but as a choice between responses to regional inefficiencies.
      Given that we do not know what will best improve the efficiency of medical care
      in a given area, experiments with financial incentives to both providers and
      individual patients should receive high priority.

PMID- 16464903
TI  - To use technology better.
AB  - Although technological innovation can improve health outcomes, the precise
      magnitude of the contribution and its value are not easily measured. The findings
      reported by Jonathan Skinner and colleagues temper the favorable conclusions
      reached by observing correlations between improvement in heart attack outcomes
      over time with spending on medical products and services. Improvements in health
      care depend not only on producing better technologies, but also on using
      technology better.

PMID- 16464904
TI  - Is technological change in medicine always worth it? The case of acute myocardial
      infarction.
AB  - We examine Medicare costs and survival gains for acute myocardial infarction
      (AMI) during 1986-2002. As David Cutler and Mark McClellan did in earlier work,
      we find that overall gains in post-AMI survival more than justified the increases
      in costs during this period. Since 1996, however, survival gains have stagnated,
      while spending has continued to increase. We also consider changes in spending
      and outcomes at the regional level. Regions experiencing the largest spending
      gains were not those realizing the greatest improvements in survival. Factors
      yielding the greatest benefits to health were not the factors that drove up
      costs, and vice versa.

PMID- 16464906
TI  - Endurance training in obese humans improves glucose tolerance and mitochondrial
      fatty acid oxidation and alters muscle lipid content.
AB  - Muscle fatty acid (FA) metabolism is impaired in obesity and insulin resistance,
      reflected by reduced rates of FA oxidation and accumulation of lipids. It has
      been suggested that interventions that increase FA oxidation may enhance insulin
      action by reducing these lipid pools. Here, we examined the effect of endurance
      training on rates of mitochondrial FA oxidation, the activity of carnitine
      palmitoyltransferase I (CPT I), and the lipid content in muscle of obese
      individuals and related these to measures of glucose tolerance. Nine obese
      subjects completed 8 wk of moderate-intensity endurance training, and muscle
      biopsies were obtained before and after training. Training significantly improved
      glucose tolerance, with a reduction in the area under the curve for glucose (P <
      0.05) and insulin (P = 0.01) during an oral glucose tolerance test. CPT I
      activity increased 250% (P = 0.001) with training and became less sensitive to
      inhibition by malonyl-CoA. This was associated with an increase in mitochondrial
      FA oxidation (+120%, P < 0.001). Training had no effect on muscle triacylglycerol
      content; however, there was a trend for training to reduce both the total
      diacylglcyerol (DAG) content (-15%, P = 0.06) and the saturated DAG-FA species (
      27%, P = 0.06). Training reduced both total ceramide content (-42%, P = 0.01) and
      the saturated ceramide species (-32%, P < 0.05). These findings suggest that the
      improved capacity for mitochondrial FA uptake and oxidation leads not only to a
      reduction in muscle lipid content but also a to change in the saturation status
      of lipids, which may, at least in part, provide a mechanism for the enhanced
      insulin action observed with endurance training in obese individuals.

PMID- 16464905
TI  - Whole genome microarray analysis of growth hormone-induced gene expression in
      bone: T-box3, a novel transcription factor, regulates osteoblast proliferation.
AB  - Growth hormone (GH) is important in the development and maintenance of bone;
      however, the IGF-dependent and -independent molecular pathways involved remain to
      be established. We used microarray analysis to evaluate GH signaling pathways in
      4-wk-old GH-deficient mice following a single injection of GH (4 mg/kg body wt)
      or PBS (n = 6/group) at 6 or 24 h after treatment. Six thousand one hundred sixty
      genes were differentially expressed at P </= 0.05, and 17% of these genes were
      identified at both time points. Several of the genes differentially expressed
      were expressed sequence tags, and the remaining genes fell into 49 Gene Ontology
      categories. For subsequent studies, we focused on T-box (Tbx)3, a novel
      transcription factor, which increased more than twofold at both time points. Real
      time RT-PCR analysis determined that pretreatment with IGF-binding protein-4 did
      not block GH-induced Tbx3 expression in vitro. Pretreatment with TNF-alpha
      blocked GH-induced Tbx3 expression. Tbx3 expression increased during osteoblast
      differentiation and following BMP-7 and Wnt3a treatment (P </= 0.05). Blocking
      Tbx3 expression by small interfering RNA decreased cell number and
      [(3)H]Thymidine incorporation (P < 0.01). In conclusion, 1) GH caused acute
      changes in several novel genes, suggesting that many GH-induced signaling
      pathways and target genes remain to be discovered; 2) because Tbx3 expression is
      regulated in osteoblasts and blockage of Tbx3 expression decreased cell number
      and DNA synthesis, we propose that Tbx3 is an important determinant of osteoblast
      cell number.

PMID- 16464907
TI  - Influence of TNF-alpha and IL-6 infusions on insulin sensitivity and expression
      of IL-18 in humans.
AB  - Inflammation is associated with insulin resistance, and both tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-6 may affect glucose uptake. TNF induces
      insulin resistance, whereas the role of IL-6 is controversial. High plasma levels
      of IL-18 are associated with insulin resistance in epidemiological studies. We
      investigated the effects of TNF and IL-6 on IL-18 gene expression in skeletal
      muscle and adipose tissue. Nine human volunteers underwent three consecutive
      interventions, receiving an infusion of recombinant human (rh)IL-6, rhTNF, and
      saline. Insulin sensitivity was assessed by measurement of whole body glucose
      uptake with the stable isotope tracer method during a euglycemic hyperinsulinemic
      clamp (20 mU.min(-1).kg(-1)), which was initiated 1 h after the IL-6-TNF-saline
      infusion. Cytokine responses were measured in plasma, muscle, and fat biopsies.
      Plasma concentrations of TNF and IL-6 increased 10- and 38-fold, respectively,
      during the cytokine infusions. Whole body insulin-mediated glucose uptake was
      significantly reduced during TNF infusion but remained unchanged during IL-6
      infusion. TNF induced IL-18 gene expression in muscle tissue, but not in adipose
      tissue, whereas IL-6 infusion had no effect on IL-18 gene expression in either
      tissue. We conclude that TNF-induced insulin resistance of whole body glucose
      uptake is associated with increased IL-18 gene expression in muscle tissue,
      indicating that TNF and IL-18 interact, and both may have important regulatory
      roles in the pathogenesis of insulin resistance.

PMID- 16464908
TI  - Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian
      tissues.
AB  - Thiazolidinediones (TZDs) are insulin-sensitizing agents used in the treatment of
      type 2 diabetes. A widely held view is that their action is secondary to
      transcriptional events that occur when TZDs bind to the nuclear receptor
      PPARgamma in the adipocyte and stimulate adipogenesis. It has been proposed that
      this increases insulin sensitivity, at least in part, by increasing the
      expression and release of adiponectin, an adipokine that activates the fuel
      sensing enzyme AMP-activated protein kinase (AMPK). In this study, we report that
      TZDs also acutely activate AMPK in skeletal muscle and other tissues by a
      mechanism that is likely independent of PPARgamma-regulated gene transcription.
      Thus incubation of isolated rat EDL muscles in medium containing 5 microM
      troglitazone for 15 min (too brief to be attributable to transcription)
      significantly increased pAMPK and pACC. At a concentration of 100 microM,
      troglitazone maximally increased these parameters and caused twofold increases in
      2-deoxy-d-glucose uptake and the oxidation of exogenous [(14)C]palmitate. Time
      course studies revealed that troglitazone-induced increases in pAMPK and pACC
      abundance at 15 min were paralleled by an increase in the AMP-to-ATP ratio and
      that by 60 min all of these parameters had returned to baseline values. Increases
      in pAMPK and pACC were also observed in skeletal muscle, liver, and adipose
      tissue in intact rats 15 min after the administration of a single dose of
      troglitazone (10 mg/kg, ip). Likewise, troglitazone and another TZD,
      pioglitazone, caused rapid increases in pAMPK and pACC of equal magnitude in
      Swiss 3T3 fibroblasts with and without sufficient PPARgamma to mediate the
      expression of target genes. The results indicate that TZDs can act within minutes
      to activate AMPK in mammalian tissues. They suggest that this effect is
      associated with a change in cellular energy state and that it is not dependent on
      PPARgamma-mediated gene transcription.

PMID- 16464909
TI  - Antioxidants N-acetyl-L-cysteine and manganese(III)tetrakis (4-benzoic
      acid)porphyrin do not prevent beta-cell dysfunction in rat islets cultured in
      high glucose for 1 wk.
AB  - We previously showed that the stimulation of heme oxygenase-1 expression by high
      glucose and hydrogen peroxide (H(2)O(2)) in cultured rat islets is prevented by
      antioxidants and suggested that this effect of high glucose results from an
      oxidative stress. However, the role of oxidative stress in high-glucose-induced
      beta-cell dysfunction is unclear. We therefore compared the preventative effects
      of N-acetyl-l-cysteine (NAC), a free radical scavenger, and
      manganese(III)tetrakis (4-benzoic acid)porphyrin (MnTBAP), a superoxide
      dismutase/catalase mimetic agent, on the alteration of stimulus-secretion
      coupling induced in rat islets by overnight exposure to hydrogen peroxide
      (H(2)O(2)-treated islets) or 1-wk culture in 30 vs. 10 mmol/l glucose (High
      glucose vs. Control islets). The features of beta-cell dysfunction differed
      between the two groups: reduced glucose-induced insulin secretion without changes
      in glucose sensitivity in H(2)O(2)-treated islets; increased sensitivity to
      glucose with parallel reductions in insulin content and maximal rate of glucose
      induced insulin secretion in High-glucose islets. The latter alterations were
      accompanied by a decrease in preproinsulin without changes in pancreatic and
      duodenal homeobox gene 1 mRNA levels. The functional alterations induced by
      H(2)O(2) were significantly prevented by addition of NAC or MnTBAP in the culture
      medium. In contrast, neither NAC nor MnTBAP affected the functional alterations
      induced by high glucose. These results suggest that beta-cell dysfunction induced
      by 1-wk culture in high glucose does not result from an increase in oxidative
      stress.

PMID- 16464911
TI  - Age, clinical presentation, and outcome of acute coronary syndromes in the
      Euroheart acute coronary syndrome survey.
AB  - AIMS: Age is one of the most powerful determinants of prognosis in myocardial
      infarction, but there is comparatively little recent data across the whole
      spectrum of acute coronary syndromes (ACS). We examined the impact of increasing
      age on clinical presentation and hospital outcome in a large sample of patients
      with ACS. METHODS AND RESULTS: Patients (n = 10 253) from the Euroheart ACS
      survey in 103 hospitals in 25 countries were investigated. There was a
      significant inverse association between the age and the likelihood of presenting
      with ST-elevation. For each decade of life, the odds of presenting with ST
      elevation decreased by 0.82 [95% confidence interval (CI) 0.79-0.84]; P < 0.0001.
      Elderly patients were considerably less often treated by cardiologists, less
      extensively investigated, and, when presenting with ST-elevation ACS, less likely
      to be treated with reperfusion. Compared with patients <55 years, the odds ratios
      of hospital mortality were 1.87 (1.21-2.88) at age 55-64, 3.70 (2.51-5.44) at age
      65-74, 6.23 (4.25-9.14) at age 75-84, and 14.5 (9.47-22.1) among patients > or
      =85 years, with no major differences across different types of admission or
      discharge diagnoses. CONCLUSION: Elderly ACS patients were less likely to present
      with ST-elevation but had substantial in-hospital mortality, yet they were
      markedly less intensively treated and investigated.

PMID- 16464910
TI  - Attenuated stress-induced catecholamine release in mice lacking the vasopressin
      V1b receptor.
AB  - Vasopressin V(1b) receptor is specifically expressed in the pituitary and
      mediates adrenocorticotropin release, thereby regulating stress responses via its
      corticotropin releasing factor-like action. In the present study we examined
      catecholamine release in response to two types of stress in mice lacking the
      V(1b) receptor gene (V(1b)R(-/-) mice) vs. wild-type mice. There were no
      significant differences in the basal plasma levels of catecholamines between the
      two genotypes. In response to stress induced by forced swimming, norepinephrine
      (NE), but not epinephrine (E) or dopamine (DA), was increased in wild-type mice,
      whereas the increases in NE and DA were not observed in V(1b)R(-/-) mice. In wild
      type mice, E, but not NE or DA, was increased in response to social isolation
      stress, whereas the increase in E was not observed in V(1b)R(-/-) mice. These
      results suggest that the V(1b) receptor regulates stress-induced catecholamine
      release. Because it has been suggested that arginine-vasopressin (AVP) is related
      to the development of depression, we also evaluated immobility time in the forced
      swimming test, and we found no significant change in V(1b)R(-/-) mice. Taken
      together, these findings suggest that, in addition to the previously elucidated
      effect on the hypothalamic-pituitary-adrenal axis, vasopressin activity via V(1b)
      receptors regulates stress-induced catecholamine release.

PMID- 16464912
TI  - Myocardial stiffness is an important determinant of the plasma brain natriuretic
      peptide concentration in patients with both diastolic and systolic heart failure.
AB  - AIMS: Plasma brain natriuretic peptide (BNP) concentration increases in
      proportion to heart failure (HF) severity. Although plasma BNP decreases to a
      certain level by optimal treatment, there is significant heterogeneity in the
      baseline value among individuals. The underlying mechanism of the steady-state
      plasma BNP levels remains still controversial. We investigated the hypothesis
      that myocardial stiffness (K(m)) is a major determinant of the plasma BNP level.
      METHODS AND RESULTS: In 19 patients with diastolic HF [DHF; left ventricular
      ejection fraction (LVEF) > or =4 5%], 18 with systolic HF (SHF; LVEF < 45%), and
      12 controls, left ventricular (LV) performance variables and the results of the
      stress-strain analyses were obtained by the combined simultaneous measurement of
      echocardiographic and haemodynamic data, and compared with the plasma BNP level.
      In DHF, a significant correlation was observed between plasma BNP and fractional
      shortening (P = 0.010), pulmonary capillary wedge pressure (P = 0.030), end
      diastolic pressure (P = 0.006), time constant of the LV isovolumic-pressure
      decline (P = 0.049), end-diastolic stress (P = 0.012), and K(m) (P = 0.004),
      respectively. In SHF, a significant correlation was observed between plasma BNP
      and end-diastolic stress (P = 0.036), chamber stiffness (P = 0.048), and K(m) (P
      = 0.003), respectively. CONCLUSION: In stable conditions, K(m) may be the most
      important determinant of the plasma BNP production in patients with both DHF and
      SHF.

PMID- 16464913
TI  - Left atrial volume predicts cardiovascular events in patients originally
      diagnosed with lone atrial fibrillation: three-decade follow-up.

PMID- 16464914
TI  - The prognostic impact of coronary flow-reserve assessed by Doppler
      echocardiography in non-ischaemic dilated cardiomyopathy.
AB  - AIMS: Coronary flow-reserve (CFR) can be impaired in non-ischaemic dilated
      cardiomyopathy (DCM), unmasking a coronary microcirculatory dysfunction of
      potential prognostic impact. The aim of the present study is to evaluate the
      prognostic value of Doppler echocardiographic-derived CFR in patients with DCM.
      METHODS AND RESULTS: We evaluated 129 DCM patients (85 male; age 62+/-11) by
      transthoracic dipyridamole (0.84 mg/kg in 10 min) stress echocardiography. All
      patients had an ejection fraction<40% (mean 32+/-7) and angiographically normal
      coronary arteries with NYHA class<or=3. CFR was assessed on left anterior
      descending artery using pulsed Doppler as the ratio of maximal peak vasodilation
      (dipyridamole) to rest diastolic flow velocity. All patients were followed-up for
      a median of 22 months. Mean CFR was 2.0+/-0.5. At individual patient analysis 46
      patients had normal (CFR>2.0) and 83 had abnormal CFR. During follow-up, 18
      patients died and 33 showed worsening of NYHA class. The worse event-free
      survival was observed in those patients with an abnormal CFR when compared with
      those having a normal CFR at high dose of dipyridamole (70 vs. 22%, at 75 months
      of follow-up, P<0.0001). In the multivariable analysis, severity of mitral
      insufficiency (HR=1.9, 95% CI=1.06-2.87), abnormal CFR (HR=4.0, 95% CI=1.1-15.6),
      resting wall motion score index (HR=6.9, 95% CI=1.5-30.7) were independent
      predictors of survival. CONCLUSION: In DCM patients, CFR is often impaired. A
      reduced CFR during vasodilator stress is an independent prognostic marker of bad
      prognosis.

PMID- 16464915
TI  - The heart, the brain, and the Kounis syndrome.

PMID- 16464916
TI  - Media and health: a continuing concern for health psychology.

PMID- 16464917
TI  - Print news and health psychology: some observations.
AB  - This commentary overviews the look of health news in American print journalism
      and the research that suggests how health news creates influence at both the
      individual and policy levels. Crime and violence are argued to be public health
      issues, but unfortunately they are often not treated as such. There is clearly
      room for improvement in all areas of health news, but unfortunately the extreme
      stress that newspapers are under to maintain their high profit margins suggests
      that the resources for such improvement are unlikely to be available. Examination
      of the Minneapolis Star Tribune's coverage of health, crime and violence
      exemplifies problematic aspects.

PMID- 16464918
TI  - Media, racism and public health psychology.
AB  - International literature has established that racism contributes to ill-health of
      migrants, ethnic minorities and indigenous peoples. Racism generally negates
      wellbeing, adversely affecting physical and psychological health. Numerous
      studies have shown that media contribute marginalizing particular ethnic and
      cultural groups depicting them primarily as problems for and threats to the
      dominant. This articles frames media representations of, and their effect on, the
      indigenous Maori of Aotearoa, New Zealand within the ongoing processes of
      colonization. We argue that reflects the media contribution to maintenance and
      naturalisation of colonial relationships and seek to include critical media
      scholarship in a critical public health psychology.

PMID- 16464919
TI  - Mediating social representations using a cartoon narrative in the context of
      HIV/AIDS: the AmaQhawe Family Project in South Africa.
AB  - Using findings from the formative evaluation of the adaptation of the
      Collaborative HIV/AIDS Adolescent Mental Health Programme (CHAMP) family-based
      intervention in South Africa, known as the 'AmaQhawe Family Project', the
      potential role of 'micro-media' using a cartoon narrative for promoting health
      enhancing behaviour change is explored. In particular, the cartoon narrative was
      found to be a useful medium for informing the development and diffusion of health
      enhancing social representations that shape the potential for health-related
      behaviour change.

PMID- 16464920
TI  - Relocating alcohol advertising research: examining socially mediated
      relationships with alcohol.
AB  - This article reviews, critiques and politicises the positivist approaches that
      presently dominate alcohol advertising health research, and considers the
      benefits of a culturalist alternative. Positivist research in this area is
      identified as: (1) atheoretical and methods-driven; (2) restricted in focus,
      leaving critical issues unconsidered; and (3) inappropriately conceptualizing the
      'normal' drinking person as rational and safe. The culturist alternative proposed
      is argued to present a more adequate framework, which can include and address
      problematic issues that are presently excluded, including: the pleasures
      associated with alcohol use, the involvements of 'normal' people in problem
      drinking, the inadequacy of present risk categories and the complexities of wider
      mediatory processes about alcohol in society. We argue for the adoption of more
      informed, culturalist approaches to alcohol advertising research.

PMID- 16464921
TI  - 'Hardcore drinking': portrayals of alcohol consumption in young women's and men's
      magazines.
AB  - Young adults and young women in particular are drinking more alcohol than ever
      before, with implications for risky behaviours and long-term health. This study
      explored the ways in which alcohol and drinking were represented in six monthly
      UK magazines (three targeted at young men, three at young women) across a three
      month period (18 magazines). We identified three main discourses across the
      texts, namely the drug alcohol; masculinity and machismo; and drinking as
      normality. These discourses constructed women's and men's drinks and drinking
      behaviours in sharp contrast. Drinking was aligned with traditional masculine
      images, although new kinds of drinks were aligned with traditional feminine
      images--and derided in men's magazines. Findings highlight how gender,
      constructed in relation to the other, is an important aspect of representations
      of drinking patterns in young adults.

PMID- 16464922
TI  - Robert Winston's Superhuman: spectacle, surveillance and patient narrative.
AB  - Health psychologists are being challenged by researchers to consider
      interdisciplinary approaches to health research, particularly around media
      representations. This article argues that the praxis and research of health
      psychology might benefit from strategic and interdisciplinary readings of media
      texts. It argues that insights from current documentary theory are important
      because they show us how documentary texts are structured and how medical
      documentary deploys techniques from medicine itself in order to effect certain
      persuasive discursive shifts in our wider culture. The article takes the BBC
      documentary series Superhuman as its example and explores this text as it
      involves media spectacle, medical surveillance of the body and of patients and
      the positioning of patient narratives of personal experiences with medical
      intervention.

PMID- 16464923
TI  - Addressing media stigma for people experiencing mental illness using an
      entertainment-education strategy.
AB  - This study examines the effects of Entertainment-Education strategy on knowledge
      acquisition about schizophrenia and stigma reduction, using pretest posttest
      control group and 2 X 3 (advocate's perspective X message style) between-subjects
      factorial design. Participants watched an accurate and empathetic movie portrayal
      of schizophrenia, followed by an educational trailer. Participants (N= 165) were
      randomly assigned to one of eight conditions (six manipulated conditions,
      control, a group who watched a trailer prior to the movie). Results showed that
      viewing an accurate and empathetic movie portrayal increased knowledge. The
      educational trailer increased not only knowledge acquisition but influenced
      stigma reduction. Structural equation modeling analysis revealed that
      entertainment and educational value of the movie mediated stigma reduction.
      Implications of this study to the mental health research and the design of
      Entertainment-Education contents are discussed.

PMID- 16464924
TI  - Informed patients and the internet: a mediated context for consultations with
      health professionals.
AB  - This article investigates how individuals' use of the Internet for finding health
      information may affect the relationship between health professionals and
      patients. It explores people's rationales for searching for information online,
      the information selection process and the implications for doctor-patient
      interactions. Qualitative interviews were conducted by email with 31 health
      information seekers. Study findings show the importance of the 'everyday' in
      orientating health information searches and of personal experience in navigating
      a multiplicity of online sources. Interviewees emphasize the primary role of the
      doctor-patient relationship for delivering health and medical information, their
      Internet searches complementing rather than opposing professional expertise.

PMID- 16464925
TI  - An interpretative phenomenological analysis of participation in a pro-anorexia
      internet site and its relationship with disordered eating.
AB  - Pro-anorexia Internet sites aim to promote, support and discuss anorexia nervosa.
      Media coverage has raised concerns that sites may increase the level of eating
      disorders. This research examines the meaning of participation in a pro-anorexia
      Internet site and its relationship with disordered eating by using an
      interpretative phenomenological analysis of fifteen separate message 'threads'
      followed over a six-week period. Four themes were identified: (1) tips and
      techniques; (2) 'ana' v. anorexia nervosa; (3) social support; and (4) need for
      anorexia. Findings suggest participation was multi-purpose, providing a coping
      function in relation to weight loss, and the contribution of sites to increased
      levels of eating disorders is not inevitable.

PMID- 16464926
TI  - Using new media to build social capital for health: a qualitative process
      evaluation study of participation in the CityNet project.
AB  - The present article presents an exploratory qualitative process evaluation study
      of 'Ambassador' participation in CityNet, an innovative information-communication
      technology-based (ICT) project that aims to build aspects of social capital and
      improve access to information and services among disadvantaged groups in
      Nottingham, UK. A purposive sample of 40 'Ambassadors' interviewees was gathered
      in three waves of data collection. The two emergent analytic themes highlighted
      how improvements in confidence, self-esteem and social networks produced via
      participation were mitigated by structural problems in devolving power within the
      project. This illustrates how concepts of power are important for understanding
      the process of health promotion interventions using new media.

PMID- 16464927
TI  - Health and digital gaming: the benefits of a community of practice.
AB  - Psychologists have a tendency to focus on the negative side of life. Our
      discipline has become preoccupied with illness rather than health. Where the
      media are concerned we explore the consequences of unhealthy messages for the
      population in general or young people in particular. This commentary breaks with
      tradition by outlining ways in which digital games can enhance health. Positive
      health consequences of gaming are explored in relation to surgical training and
      therapeutic interventions, physical exercise, health education and community
      participation.

PMID- 16464928
TI  - Developing a critical media research agenda for health psychology.
AB  - This article outlines reasons why psychologists should concern themselves with
      media processes, noting how media are central to contemporary life and heavily
      implicated in the construction of shared understandings of health. We contend
      that the present research focus is substantially medicalized, privileging the
      investigation and framing of certain topics, such as the portrayal of health
      professionals, medical practices, specific diseases and lifestyle-orientated
      interventions, and restricting attention to social determinants of health as
      appropriate topics for investigation. We propose an extended agenda for media
      health research to include structural health concerns, such as crime, poverty,
      homelessness and housing and social capital.

PMID- 16464929
TI  - Primary care in Indonesia.

PMID- 16464930
TI  - Consumer satisfaction and child behaviour problems in child and adolescent mental
      health services.
AB  - Consumer satisfaction with health care is one of the goals of health care
      delivery. Information on what affects satisfaction helps health care providers to
      deliver patient-centred care. The aim of this study was to explore the
      relationship between young persons' symptoms and satisfaction with Child and
      Adolescent Mental Health Services (CAMHS). It also examined differences in
      satisfaction of the parent/carer and their child. Self-report questionnaires were
      used to gather information from respondents. High levels of satisfaction were
      reported, although children and adolescents were less satisfied than
      parents/carers. Young people with self-reported conduct problems were least
      satisfied with CAMHS, as were those who rated their problems as having a
      significant impact on their lives. There was no relationship between carer
      reported 'caseness' and carer satisfaction with services. Further exploration of
      the needs and expectations of young people who have behavioural difficulties is
      necessary so that their needs are better understood and expectations met.

PMID- 16464931
TI  - Growing up and moving on in rheumatology: development and preliminary evaluation
      of a transitional care programme for a multicentre cohort of adolescents with
      juvenile idiopathic arthritis.
AB  - This article describes the development and initial evaluation of an evidence
      based transitional care programme recently implemented in a multicentre
      controlled trial in the United Kingdom. The individual components of the
      programme are described. Evaluation of the acceptability and utilization of these
      components employed questionnaires administered to users (adolescents with
      juvenile idiopathic arthritis and their parents) and providers (rheumatology
      health professionals). The results confirm the acceptability and utilization of
      the programme components in addition to further innovative developments during
      the course of the study. In conclusion, the evidence-based transitional care
      programme components reported here are acceptable and useful to both user and
      provider and are potentially feasible in clinical practice in a revised format.

PMID- 16464932
TI  - Differences in parenting needs of fathers of children with chronic conditions
      related to family income.
AB  - Children with chronic conditions now survive longer than has been true
      historically, creating a need to promote optimal growth and development for
      themselves, their family members and the family as a whole. This article
      reporting a midwestern United States study compares the concerns and coping
      strategies of fathers of chronically-ill children with household annual incomes
      less than $50,000 with fathers of chronically-ill children with household incomes
      of $50,000 or more. The sample of 48 fathers completed the Hymovich Family
      Perception Inventory anonymously. The results revealed differences in the
      parenting concerns of fathers related to family income. The low-income fathers
      expressed a desire for more knowledge about the children's condition and worries
      about family finances. Professional anticipatory guidance and dissemination of
      information holds promise for providing the support needed by fathers of children
      with chronic conditions, particularly those with lower household incomes.

PMID- 16464933
TI  - Developing the children's nursing workforce: profile, first jobs and future plans
      of newly qualified diplomates.
AB  - Concerns regarding the number of children's nurses persist despite initiatives
      designed to reverse this trend. Recruiting and retaining a diverse nursing
      workforce is high on the policy agenda, particularly since the publication of the
      National Service Framework for Children, Young People and Maternity Services.
      This article reports findings from the first phase of a longitudinal study
      investigating the careers of child branch diplomates, focusing on the cohort's
      profile, first jobs and future plans. Findings suggest there is considerable
      scope to increase diversity in the children's nursing workforce. Child health
      diplomates indicate little sign of early attrition from nursing at qualification.
      Continuing professional development is a high priority for many child health
      nurses at the outset of their careers. These findings provide an important
      benchmark for later stages of child branch nurses' careers.

PMID- 16464934
TI  - The moral experience of parents regarding life-support decisions for their
      critically-ill children: a preliminary study in France.
AB  - The common paediatric critical care practice in France is for physicians (rather
      than parents) to maintain the ultimate responsibility for lifesupport decisions
      in children. Some French literature asserts that it is inappropriate for parents
      to bear such responsibilities because they do not have the required knowledge and
      should be protected from feeling culpable for such decisions. The aim of this
      grounded theory preliminary study was to examine the moral experience of parents
      of critically-ill children that required life-support decisions in France. A
      convenience purposive sample of seven parents was recruited in Paris. Five
      principal themes emerged as significant from these interviews: (1) a need for
      more information; (2) physicians should be responsible for life-support
      decisions; (3) the child's concerns and wishes need to be better heard; (4)
      maternal guilt; and (5) physicians require better training in parent
      communication. These findings raise important issues for clinical practice and
      further research in France.

PMID- 16464935
TI  - Mass media interventions for promoting HIV testing: Cochrane systematic review.

PMID- 16464936
TI  - Risk management, or just a different risk?
AB  - BACKGROUND: National reporting of adverse incidents has resulted in a number of
      clinical alerts being issued. Despite a lack of evidence, these alerts are often
      accompanied by a mandatory requirement to alter practice. There is likely to be
      clinician resistance to such a method of change management, particularly where
      evidence of safety is missing. AIM: To determine the level of implementation
      within neonatal units of an alert requiring the change from litmus to pH paper to
      test nasogastric tube position. METHOD: A questionnaire sent to all neonatal
      units in the United Kingdom with more than 12 cots. RESULTS: From the 207
      questionnaires sent, there were 165 (80%) responses. Fifty five percent of units
      were still using litmus. All continued to use supplementary tests not recommended
      in best practice statements issued at the time of the alert. There was
      considerable variation in the pH value at which it was considered safe to feed.
      CONCLUSIONS: Nine months after the alert, more than half the units had not
      changed to pH paper, and supplementary methods of testing were still being used.
      The wide range of pH values highlights the uncertainty about the "normal" gastric
      pH in the newborn. The evidence that, in neonatal units, changing to pH paper is
      safer than the long established use of litmus is lacking. Recommendations for
      change in practice must be based on good information and not seen just as a "knee
      jerk" response to adverse incidents.

PMID- 16464937
TI  - Facilitation of neonatal endotracheal intubation with mivacurium and fentanyl in
      the neonatal intensive care unit.
AB  - BACKGROUND: Endotracheal intubation in the neonate is painful and is associated
      with adverse physiological effects. Some premedication regimens have been shown
      to reduce these effects, but the optimal regimen is not yet determined. METHOD:
      Data on semi-elective intubations were prospectively collected in the neonatal
      intensive care unit over a six month period. Patients received 20 microg/kg
      atropine, 200 microg/kg mivacurium (a non-depolarising muscle relaxant) followed
      by 5 microg/kg fentanyl. RESULTS: Thirty three patients were electively intubated
      during this time period. The primary reason for intubation was surfactant
      administration (53%). Median (range) birth weight, gestational age, and age at
      intubation were 1360 g (675-4200), 29 weeks (25-38), and 33 hours (1-624)
      respectively. Twenty two of the infants were intubated on the first attempt.
      Median duration from initial insertion of the laryngoscope to successful
      intubation was 60 seconds (15 seconds to 20 minutes). In 18 cases, the first
      attempt was by a trainee with no previous successful intubation experience, 10 of
      whom intubated within two attempts. Muscle relaxation occurred at a mean (SD) of
      94 (51) seconds, and mean (range) time to return of spontaneous movements was 937
      seconds (480-1800). Intubation conditions were scored as excellent using a
      validated intubation scale. CONCLUSION: Effective analgesia can be administered
      and intubation performed with some brief desaturations, even when junior
      personnel are being taught their first intubation. In this first report of
      mivacurium for intubation in the newborn, effective bag and mask ventilation was
      easily achieved during muscle relaxation and was associated with excellent
      intubation conditions, permitting a high success rate for inexperienced
      personnel.

PMID- 16464938
TI  - Perinatal renal venous thrombosis: presenting renal length predicts outcome.
AB  - BACKGROUND: Renal venous thrombosis (RVT) is the most common form of venous
      thrombosis in neonates, causing both acute and long term kidney dysfunction.
      Historical predisposing factors include dehydration, maternal diabetes, and
      umbilical catheters, but recent reports highlight associations with prothrombotic
      abnormalities. STUDY: Twenty three patients with neonatal RVT were analysed over
      15 years. Predisposing factors, presentation, and procoagulant status were
      compared with renal outcome using multilevel modelling. RESULTS: Median
      presentation was on day 1: 19/23 (83%) had pre/perinatal problems, including
      fetal distress (14), intrauterine growth retardation (five), and pre-identified
      renal abnormalities (two); 8/18 (44%) had procoagulant abnormalities,
      particularly factor V Leiden mutations (4/18). Long term abnormalities were
      detected in 28/34 (82%) affected kidneys; mean glomerular filtration rate was
      93.6 versus 70.2 ml/min/1.73 m2 in unilateral versus bilateral cases (difference
      23.4; 95% confidence interval 6.4 to 40.4; p = 0.01). No correlation was observed
      between procoagulant tendencies and outcome, but presenting renal length had a
      significant negative correlation: mean fall in estimated single kidney glomerular
      filtration rate was 3 ml/min/1.73 m2 (95% confidence interval 3.7 to -2.2; p =
      0.001) per 1 mm increase, and kidneys larger than 6 cm at presentation never had
      a normal outcome. CONCLUSIONS: This subgroup of neonatal RVT would be better
      termed perinatal RVT to reflect antenatal and birth related antecedents.
      Prothrombotic defects should be considered in all patients with perinatal RVT.
      Kidney length at presentation correlated negatively with renal outcome. The
      latter, novel observation raises the question of whether larger organs should be
      treated more aggressively in future.

PMID- 16464939
TI  - A PRKAR1A mutation associated with primary pigmented nodular adrenocortical
      disease in 12 kindreds.
AB  - CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause
      of corticotropin-independent Cushing syndrome, can be part of Carney complex
      (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty
      skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i).
      Germline PRKAR1A-inactivating mutations have been observed in both CNC and
      iPPNAD, but with no apparent genotype-phenotype correlation. OBJECTIVE: The
      objectives of the study were a detailed phenotyping for CNC manifestations in 12
      kindreds bearing the same PRKAR1A mutation and a study of the consequences of the
      mutation and a potential founder effect. DESIGN: The study consisted of
      descriptive case reports. SETTING: The study was conducted at two referral
      centers. PATIENTS: The patients described in this study were referred for PRKAR1A
      gene mutation analysis because of a diagnosis of apparently iPPNAD. RESULTS: We
      describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12
      unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of
      the patients had no family history; in two, there was a family history of iPPNAD.
      Only one patient met the criteria for CNC. Relatives carrying the same mutation
      had no manifestations of CNC or PPNAD, suggesting a low penetrance of this
      PRKAR1A defect. A founder effect was excluded by extensive genotyping of
      chromosome 17 markers. CONCLUSIONS: In conclusion, a small intronic deletion of
      the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first
      PRKAR1A genetic defect to have an association with a specific phenotype.

PMID- 16464940
TI  - Identification of new variants of human BMP15 gene in a large cohort of women
      with premature ovarian failure.
AB  - CONTEXT: Premature ovarian failure (POF) is a cause of female infertility
      characterized by primary (PA) or secondary amenorrhea (SA) and elevated
      gonadotropins. The pathogenesis is unknown in most cases. We recently reported
      two sisters with PA carrying a heterozygous mutation of BMP15 gene (locus
      Xp11.2), but the prevalence of BMP15 variations in the POF population is unknown.
      OBJECTIVE: The objective of the study was to verify the involvement of BMP15
      variations in a large POF population. DESIGN AND SUBJECTS: Genetic screening of
      166 unrelated patients with idiopathic POF (25 PA, 141 SA) and controls (group A:
      95 women with menopause beyond 50 yr of age; group B: 86 women and 30 men from
      the general population) of Caucasian origin. RESULTS: Investigation revealed four
      heterozygous variations affecting the proregion of BMP15. The previously reported
      p.Y235C mutation occurred in one and three novel variants in eight patients: two
      missense alterations (p.R68W in one case, p.A180T in five) and one insertion
      (p.262insLeu) in two cases. The p.262insLeu was found in five controls of group
      A, thus diminishing its potential biological impact, whereas the other three
      variants were not present in any of the controls. All new mutations were found in
      SA cases. CONCLUSION: We describe the significant association of heterozygous
      BMP15 gene variants with the POF phenotype in humans (seven of 166 patients:
      4.2%; P < 0.003 vs. controls). These findings are consistent with the critical
      role played by BMP15 in human folliculogenesis.

PMID- 16464941
TI  - Smaller left anterior cingulate cortex volumes are associated with impaired
      hypothalamic-pituitary-adrenal axis regulation in healthy elderly men.
AB  - CONTEXT: Studies in animals suggest that the limbic prefrontal cortex, including
      the anterior cingulate cortex, is involved in regulation of the hypothalamic
      pituitary-adrenal (HPA) axis, but human data are lacking. OBJECTIVE: This study
      tested the hypothesis that smaller anterior cingulate cortex volumes are
      associated with HPA axis dysregulation in healthy older men. DESIGN AND
      PARTICIPANTS: Comparison was made of volumes of bilateral anterior cingulate
      cortex, hippocampus, and superior frontal gyrus (control region) volumes in two
      groups of 10 healthy men, aged 65-70 yr, who showed nonsuppression or suppression
      of cortisol levels in response to low dose (250 microg) dexamethasone. Analysis
      of brain volumes was performed blind to the cortisol levels. SETTING: This study
      was performed at a tertiary care clinical research center. RESULTS:
      Nonsuppressors had significantly smaller left anterior cingulate cortex volumes
      than suppressors (5757 vs. 7817 mm(3); P = 0.01). Right anterior cingulate
      cortex, bilateral hippocampus, and bilateral superior frontal gyrus volumes were
      not significantly different between nonsuppressors and suppressors. CONCLUSIONS:
      Smaller left anterior cingulate cortex volumes may be associated with HPA axis
      dysregulation in humans. These results substantiate evidence from animal studies
      indicating an important role for the anterior cingulate cortex in
      suprahypothalamic feedback regulation of the HPA axis. The results also have
      implications for disorders in which HPA axis dysregulation and abnormalities of
      the anterior cingulate cortex are frequently observed, such as depression and
      Alzheimer's disease.

PMID- 16464942
TI  - A mutant signal transducer and activator of transcription 5b, associated with
      growth hormone insensitivity and insulin-like growth factor-I deficiency, cannot
      function as a signal transducer or transcription factor.
AB  - CONTEXT: A natural missense mutation in the signal transducer and activator of
      transcription (STAT) 5b gene was recently identified in association with a female
      patient presenting with severe growth failure and immune dysfunction. The
      mutation results in an alanine to proline substitution at residue 630 (A630P) in
      the src-homology-2 domain, a region essential for docking of STATs to phospho
      tyrosines on activated receptors, STAT dimerization, and stabilization of phospho
      STAT-DNA interactions. OBJECTIVE: The purpose of this study was to explore the
      molecular mechanisms underlying the GH insensitivity and IGF-I deficiency caused
      by the A630P-mutated STAT5b. RESULTS: In reconstitution experiments using HEK293
      cells, both GH and interferon-gamma were unable to activate mutant STAT5b
      (A630P), as demonstrated by lack of immunodetectable phospho-tyrosyl-STAT5b
      (A630P) and inability to drive luciferase reporter activity. However, the Src
      family of nonreceptor kinases [constitutively active v-src and epithelial growth
      factor-induced c-src] tyrosine-phosphorylated STAT5b(A630P). The v-src-induced
      phospho-STAT5b(A630P) translocated to the nucleus but, unlike wild-type Stat5b,
      was unable to bind DNA. CONCLUSIONS: The A630P mutation disrupts the src-homology
      2 architecture such that: 1) mutant STAT5b most likely cannot dock to phospho
      tyrosines on ligand-activated receptors; and 2) stable interactions with DNA are
      prevented. Because STAT5b (A630P) is an inefficient signal transducer and
      transcription factor, the detrimental impact on signaling pathways important for
      normal growth and immunity explains, in part, the complex clinical phenotype of
      GH insensitivity and immune dysfunction.

PMID- 16464943
TI  - A novel thyroid hormone receptor-beta mutation that fails to bind nuclear
      receptor corepressor in a patient as an apparent cause of severe, predominantly
      pituitary resistance to thyroid hormone.
AB  - CONTEXT: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome
      of variable tissue hyporesponsiveness to thyroid hormone (TH). OBJECTIVE: We
      report a newborn who presented with severe RTH (Mkar) with serum TSH 1500
      mU/liter and free T(3) greater than 50 pm (normal 3.1-9.4) and free T(4) 25.3 pm
      (normal 12-22). We hypothesized that the RTH was due to reduced ligand binding
      and/or abnormal interaction with nuclear cofactors. DESIGN: These were
      prospective in vivo and in vitro studies. SETTING: The study was conducted at a
      tertiary care university hospital. PATIENTS: Patients included a newborn child
      and two other subjects with RTH. INTERVENTION: The effect of various TH-lowering
      agents in the subject with RTH was studied. In vitro studies including EMSA and
      mammalian two-hybrid assay as well as in vitro transfection studies were
      conducted. MAIN OUTCOME MEASURES: Sequencing of the TH receptor (TR)beta and in
      vitro measurements of receptor-cofactor interaction were measured. RESULTS:
      Sequencing of the TRbeta demonstrated a de novo heterozygous mutation,
      1590_1591insT, resulting in a frameshift producing a mutant TRbeta (mutTR)-beta
      with a 28-amino acid (aa) nonsense sequence and 2-amino acid carboxyl-terminal
      extension. The Mkar mutation was evaluated in comparison to three other TRbeta
      frameshift mutations in the carboxyl terminus. EMSA demonstrated that the Mkar
      mutTRbeta1 had impaired ability to recruit nuclear receptor corepressor but
      intact association with silencing mediator of retinoid and thyroid receptor
      (SMRT). CONCLUSION: Our data suggest that alterations in codons 436-453 in helix
      11 result in significantly diminished association with nuclear receptor
      corepressor but not SMRT. This novel mutTRbeta demonstrates nuclear corepressor
      specificity that results in severe predominantly pituitary RTH due to impaired
      release of SMRT.

PMID- 16464944
TI  - Increased cortisol in the cerebrospinal fluid of women with functional
      hypothalamic amenorrhea.
AB  - CONTEXT: The proximate cause of functional hypothalamic amenorrhea (FHA) is
      reduced GnRH drive. The concomitant increase in circulating cortisol suggests
      that psychogenic stress plays an etiologic role, but others have argued for a
      strictly metabolic cause, such as undernutrition or excessive exercise. Indeed,
      our finding that the cerebrospinal fluid (CSF) concentration of CRH was not
      elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal
      activation in FHA and, therefore, we wondered whether central cortisol levels
      were elevated. OBJECTIVE: We tested the null hypothesis that CSF cortisol levels
      would be comparable in FHA and eumenorrheic women (EW). DESIGN: The study is a
      cross-sectional comparison. SETTING: The study was set in a general clinical
      research center at an academic medical center. PARTICIPANTS: Fifteen women with
      FHA who were of normal body weight and 14 EW participated. INTERVENTION: Blood
      samples were collected at 15-min intervals for 24 h, followed by procurement of
      25 ml CSF. MAIN OUTCOME MEASURES: Cortisol, cortisol-binding globulin (CBG), and
      SHBG levels in blood and CSF were the main outcome measures. RESULTS: CSF
      cortisol concentrations were 30% greater when serum cortisol was 16% higher in
      FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and,
      thus, the circulating free cortisol index was similar in FHA and EW. Because CBG
      and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound.
      CONCLUSIONS: The hypothalamic-pituitary-adrenal axis is activated in FHA. The
      maintenance of CRH drive despite increased CSF cortisol indicates resistance to
      cortisol feedback inhibition. The mechanisms mediating feedback resistance likely
      involve altered hippocampal corticosteroid reception and serotonergic and
      GABAergic neuromodulation.

PMID- 16464946
TI  - Myostatin is a human placental product that regulates glucose uptake.
AB  - CONTEXT: Myostatin is a member of the TGF-beta superfamily and is primarily known
      for its ability to inhibit muscle growth. It also has actions on glucose
      metabolism. We hypothesized that it may act as a paracrine regulator of glucose
      uptake in the placenta, potentially contributing to fetal and placental growth.
      OBJECTIVES: The objective of this study was to determine whether myostatin is
      present in and formed by the human placenta and to evaluate its effects on
      glucose uptake. MATERIALS AND METHODS: Myostatin protein and mRNA were measured
      using Western immunoblotting and real-time PCR, respectively. Glucose uptake was
      assessed by uptake of radiolabeled deoxyglucose in vitro. Placental tissues were
      obtained at term (n = 8), preterm (n = 8; 24-34 wk), and early in pregnancy (n =
      6; 9-13 wk). RESULTS: Human placentas were shown to express myostatin protein,
      with a significantly lower expression in term samples compared with samples
      collected in preterm samples. Human placentas express myostatin mRNA throughout
      gestation, which does not change. Myostatin treatment of human term placental
      explants resulted in an increase in deoxyglucose uptake compared with controls.
      CONCLUSIONS: Myostatin is synthesized, released, and acts within the human
      placenta. It contributes to placental glucose homeostasis and may be a
      therapeutic target in diseases ranging from placental insufficiency to diabetes
      in pregnancy.

PMID- 16464945
TI  - A novel selective progesterone receptor modulator asoprisnil (J867) inhibits
      proliferation and induces apoptosis in cultured human uterine leiomyoma cells in
      the absence of comparable effects on myometrial cells.
AB  - CONTEXT: Asoprisnil, a selective progesterone (P4) receptor (PR) modulator (SPRM)
      with mixed P4 agonist/antagonist activities, reduces uterine leiomyoma volume in
      a dose-dependent manner in the presence of follicular phase estrogen
      concentrations. The evidence from clinical studies suggests that asoprisnil may
      directly target the uterine leiomyomata. OBJECTIVE AND METHODS: The present study
      evaluated the effects of asoprisnil on cell proliferation, the expression of
      apoptosis-related proteins, and apoptosis in cultured human uterine leiomyoma
      cells and matched normal myometrial cells. PR-A and PR-B expression in the two
      types of cells was comparatively evaluated. Cell proliferation, proliferating
      cell nuclear antigen (PCNA)-positive rate, and TUNEL-positive rate were assessed
      by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium assay, immunocytochemistry, and terminal deoxynucleotidyl transferase
      mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay,
      respectively. The expression of apoptosis-related proteins and PR was assessed by
      Western blot analysis. RESULTS: Compared with untreated cultures, asoprisnil
      decreased the number of viable cultured cells, the PCNA-positive rate, and PCNA
      protein expression in cultured leiomyoma cells. Asoprisnil increased the TUNEL
      positive rate, cleaved caspase-3, and cleaved poly(adenosine 5'-diphosphate
      ribose) polymerase expression and decreased Bcl-2 protein expression in cultured
      leiomyoma cells. These effects were dose and time dependent. In cultured
      myometrial cells, however, asoprisnil did not affect cell proliferation and
      apoptosis. PR-B expression was elevated in cultured leiomyoma cells compared with
      cultured myometrial cells, whereas no differences in PR-A expression were noted
      between the two cell types. CONCLUSIONS: These results show that asoprisnil
      inhibits proliferation and induces apoptosis in cultured uterine leiomyoma cells
      in the absence of comparable effects on cultured normal myometrial cells,
      suggesting a cell type-specific effect.

PMID- 16464947
TI  - Increased activation of nuclear factor kappaB triggers inflammation and insulin
      resistance in polycystic ovary syndrome.
AB  - CONTEXT: Insulin resistance and chronic low level inflammation are often present
      in women with polycystic ovary syndrome (PCOS). OBJECTIVE: The purpose of this
      study was to determine the effects of hyperglycemia on nuclear factor kappaB
      (NFkappaB) activation and inhibitory kappaB (IkappaB) from mononuclear cells
      (MNC) in PCOS. DESIGN AND SETTING: This was a prospective controlled study
      conducted at an academic medical center. PATIENTS: The study population consisted
      of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and
      body composition-matched controls (eight lean, eight obese). MAIN OUTCOME
      MEASURES: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose
      tolerance test (IS(OGTT)). Intranuclear NFkappaB and IkappaB protein expression
      were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose
      ingestion. RESULTS: IS(OGTT) was lower in PCOS compared with controls (3.3 +/-
      0.3 vs. 6.4 +/- 0.9, P < 0.004). The percent change in intranuclear NFkappaB was
      higher in lean and obese PCOS compared with lean controls (42.5 +/- 19.1 and 54.5
      +/- 12.5 vs. -14.1 +/- 10.9, P < 0.006). The percent change in intranuclear
      NFkappaB correlated positively with 2-h post-glucose ingestion levels (r = 0.37;
      P < 0.04) and plasma testosterone (r = 0.49; P < 0.006) and correlated negatively
      with IS(OGTT) (r = 0.39; P < 0.04). The percent change in IkappaB was lower in
      lean and obese PCOS compared with lean controls (-22.3 +/- 3.2 and -17.0 +/- 5.0
      vs. 8.4 +/- 11.8, P < 0.02). CONCLUSION: In response to hyperglycemia,
      intranuclear NFkappaB increases and IkappaB decreases in MNC of women with PCOS
      independent of obesity. This may represent a cardinal inflammatory signal that
      contributes to the induction of insulin resistance and hyperandrogenism in PCOS.

PMID- 16464948
TI  - A common polymorphism renders the luteinizing hormone receptor protein more
      active by improving signal peptide function and predicts adverse outcome in
      breast cancer patients.
AB  - CONTEXT: Epidemiological and animal studies indicate a carcinogenic role of
      estrogens in breast tissue. The pituitary gonadotropin LH is an important
      regulator of estrogen production in premenopausal women, whereas even in women
      after menopause, 10-25% of ovarian steroid hormone production is LH dependent.
      OBJECTIVE: We hypothesized that an LH receptor (LHR) gene variant may affect LHR
      function and thereby influence disease outcome in breast cancer patients. DESIGN:
      The association of a polymorphic CTCCAG (Leu-Gln) insertion (insLQ), in the
      signal peptide encoded by exon 1 of the LHR gene with breast cancer risk,
      (disease-free) survival, and clinicopathological features was studied in a large
      cohort of 751 breast cancer patients with complete follow-up. Functional analysis
      of the insLQ-LHR and non-LQ-LHR (no LQ insertion) was carried out using
      transfection studies. RESULTS: We found a significant association between the
      insLQ-LHR and a shorter disease-free survival (hazard ratio, 1.34; confidence
      interval, 1.11-1.63; P = 0.003). The mechanism of the effect of insLQ on LHR
      function involves increased receptor sensitivity (insLQ-LHR has a 1.9 times lower
      EC(50) than non-LQ-LHR; P = 0.02) and plasma membrane expression (insLQ-LHR has
      1.4 times higher B(max); P = 0.0006) rendering the insLQ-LHR allele more active.
      CONCLUSIONS: The insLQ polymorphism increases LHR activity, thereby shortening
      breast cancer disease-free survival, probably by increasing estrogen exposure in
      female carriers.

PMID- 16464949
TI  - Body composition and adiponectin serum concentrations in adult patients with
      cystic fibrosis.
AB  - CONTEXT: Cystic fibrosis (CF) is a disease characterized by weight loss and
      chronic low-grade inflammation. OBJECTIVE: The objective of the study was to
      assess changes in body composition and the serum concentrations of adiponectin, a
      marker of negative energy balance and insulin sensitivity, in adult patients with
      CF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at
      an outpatient clinic of the University Hospital of Basel, Switzerland.
      PARTICIPANTS: Twenty-four stable adult CF patients and 24 healthy controls,
      matched for body mass index, age, sex, and hormonal therapy in women participated
      in the study. MAIN OUTCOME MEASURES: Changes in body composition (assessed by
      dual x-ray absorptiometry) and serum adiponectin levels were measured. RESULTS:
      Body mass index, percent fat mass (in percentage of body weight), and percent
      lean body mass were similar in patients and controls, whereas central fat
      accumulation was increased [trunk to extremity fat ratio 1.2 (0.99-1.51) vs. 0.99
      (0.81-1.25), P = 0.01] in patients with CF, compared with controls. Decreased
      lean mass and increased highly sensitive C-reactive protein levels were
      independently associated with worse lung function in CF patients. Despite similar
      insulin resistance (homeostasis model assessment) and similar SHBG serum
      concentrations, the serum concentrations of adiponectin were higher in CF
      patients, compared with controls, independent of other confounders (P = 0.01).
      CONCLUSIONS: Central fat accumulation is increased in patients with CF. It is
      postulated that the energy deficit-induced increase in serum adiponectin could
      explain the preservation of insulin sensitivity in these patients despite the
      increase in central fat and in highly sensitive C-reactive protein serum
      concentrations and could prevent a further deterioration of protein catabolism.

PMID- 16464951
TI  - Function of estrogen-related receptor alpha in human endometrial cancer.
AB  - INTRODUCTION: The estrogen-related receptor alpha (ERRalpha) is an orphan member
      of the nuclear receptor superfamily that is closely related to estrogen receptor
      alpha (ERalpha). ERRalpha binds an estrogen response element (ERE), directly
      competes with ERalpha for binding ERE, and represses ERE-dependent transcription
      in MCF-7 cells, ER-positive breast cancer cells. OBJECTIVE: We investigated
      whether ERRalpha modulate some ER-dependent activities in endometrial cancer.
      METHOD: We investigated protein and mRNA expression of ERRalpha in endometrial
      cancer using immunohistochemistry and RT-PCR, respectively. After transient
      transfection using the ERRalpha expression vector (pCI-ERRalpha) or ERRalphaSi,
      which suppressed the expression of endogenous ERRalpha, Ishikawa cells were
      assayed for ERE-dependent luciferase activity. Cells stably overexpressing
      ERRalpha were generated and compared with estrogen-dependent and -independent
      cell growth. RESULT: ERRalpha was detected in human endometrial cancer tissues by
      immunohistochemistry. An RT-PCR study showed that mRNA of ERRalpha was expressed
      in four endometrial cancer cell lines (Ishikawa, Hec1a, KLE, and SNGII) and 11
      human endometrial tissues. Overexpression of ERRalpha repressed estrogen-induced
      ERE-dependent transcriptional activity in Ishikawa cells. After transfection with
      ERRalphaSi1, the expression of endogenous ERRalpha decreased to 0.5-fold, and
      estrogen-induced ERE luciferase activity increased to 1.5-fold. The cells stably
      overexpressing ERRalpha grew up more slowly than control cells in the presence of
      10 nm estradiol. CONCLUSION: ERRalpha is expressed in human endometrial cancer
      tissues and cell lines and suppresses ERE-dependent transcriptional activity in
      the presence of estrogen. ERRalpha modulates estrogen-induced activity in
      estrogen-dependent endometrial cancer.

PMID- 16464950
TI  - Fetal growth and the adrenocortical response to psychological stress.
AB  - CONTEXT: Experimental studies in animals show that adverse prenatal environments
      lead to lifelong alterations in the activity of the hypothalamic-pituitary
      adrenal axis, which mediates the stress response through secretion of
      glucocorticoid hormones. The extent to which such prenatal hypothalamic-pituitary
      adrenal axis adaptations occur in humans is unknown. OBJECTIVE: The objective of
      the study was to determine whether smaller but otherwise healthy term babies are
      more likely to demonstrate increased glucocorticoid responses to psychological
      stress in childhood. DESIGN AND PARTICIPANTS: This was a cross-sectional study of
      68 boys and 72 girls (aged 7-9 yr) who have been followed up since 12 wk
      gestation when their mothers took part in a study of healthy children born in
      Southampton, United Kingdom. MAIN OUTCOME MEASURE: Salivary cortisol responses to
      psychological stress were measured. RESULTS: In boys, birth weight was inversely
      related to salivary cortisol responses to stress (r = -0.56, P < 0.001) but not
      morning cortisol levels, whereas in girls, morning peak cortisol was inversely
      related to birth weight (r = -0.36, P < 0.05). These associations were
      independent of gestational age and potential confounding factors including
      obesity, social class, and educational achievement. CONCLUSIONS: This study
      suggests that processes occurring during fetal life, resulting in smaller
      newborns, have a lasting effect on adrenocortical responses to stress in boys and
      on basal adrenocortical activity in girls. Given the known associations between
      small alterations in adrenocortical activity and features of the metabolic
      syndrome such as raised blood pressure and glucose intolerance, these effects
      warrant further investigation of their potential impact on the future health of
      prepubertal children.

PMID- 16464952
TI  - Absence of increased height velocity in the first year of life in untreated
      children with simple virilizing congenital adrenal hyperplasia.
AB  - CONTEXT: In congenital adrenal hyperplasia (CAH), elevation of adrenal androgens
      leads to accelerated growth and bone maturation with compromised adult height.
      OBJECTIVE/PATIENTS: The objective of the study was to analyze retrospectively
      early growth and bone maturation in 17 untreated simple virilizing (SV) CAH
      patients. SETTING: The study was conducted at Radboud University Nijmegen Medical
      Centre. INTERVENTIONS: Growth data were collected until time of diagnosis. Height
      was expressed as height sd score and corrected for target height. Bone maturation
      was determined and expressed as bone age acceleration. MAIN OUTCOME MEASURES:
      Growth pattern and bone maturation were measured before the diagnosis. RESULTS:
      In the term group (n = 11), there was no increase in height sd score and
      corrected for target height in the first year of life [-0.1 sd/yr; 95% confidence
      interval (CI) -0.5, 0.3] with a consecutive significant (P < 0.001) increase up
      to 0.9 sd/yr (95% CI 0.7, 1.0). In the premature group (n = 3), there was a catch
      up growth of 1.6 sd/yr (95% CI 0.9, 2.3) in the first year followed by a growth
      of 1.1 sd/yr (95% CI 0.9, 1.5) in the following years. There was a positive
      linear correlation between bone age acceleration and age of diagnosis (r = 0.8).
      CONCLUSIONS: Height velocity and bone maturation are not increased in untreated
      children with mild forms of SV CAH in the first year of life. After this period
      there is a progressive increase in height velocity and bone maturation in strong
      relation to the duration of androgen exposition. This observation has
      implications for the dose of glucocorticoids to be used in SV CAH patients in the
      first year of life.

PMID- 16464954
TI  - High serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I)
      during high-dose GH treatment in short children born small for gestational age.
AB  - CONTEXT: Epidemiological studies have indicated that high serum levels of GH and
      IGF-I are associated with long-term risks. OBJECTIVE: The objective of the study
      was to evaluate the changes in serum levels of GH during overnight profiles, IGF
      I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA)
      children during GH treatment with two doses. PATIENTS: Thirty-six prepubertal
      short SGA children were the subjects of this study. INTERVENTION: Subjects
      received 1 (group A) or 2 (group B) mg GH/m(2).d. MAIN OUTCOME MEASURES: At
      baseline and after 6 months of GH treatment, overnight GH profiles were
      performed, and serum IGF-I and IGFBP-3 levels were measured. RESULTS: After 6
      months, group B had significantly higher GH levels during the profile (mean,
      maximum, and area under the curve above zero line) than group A (P < 0.009). In
      group B, maximum GH levels increased from 43.9-161 mU/liter (P < 0.0002), and in
      group A, from 57.2-104 mU/liter (P = 0.002). During the profile (i.e. 12 h per
      day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A
      (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio sd scores increased
      significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P =
      0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the
      children had IGF-I levels in the highest quintile during GH treatment compared
      with 19% in group A. CONCLUSION: Our study shows that high-dose GH treatment in
      short SGA children results in high serum GH and IGF-I levels in most children. We
      recommend monitoring IGF-I levels during GH therapy to ensure that these remain
      within the normal range.

PMID- 16464953
TI  - Specific human leukocyte antigen DQ influence on expression of antiislet
      autoantibodies and progression to type 1 diabetes.
AB  - CONTEXT: Human leukocyte antigen (HLA) DQ haplotypes have the strongest genetic
      association with type 1 diabetes (T1DM) risk. OBJECTIVE: The objective of the
      study was to analyze whether HLA DQ alleles influence the development of
      antiislet autoantibodies, the progression to T1DM among autoantibody-positive
      relatives, or both. DESIGN: The Diabetes Prevention Trial-1 screened more than
      90,000 nondiabetic relatives of patients for cytoplasmic islet-cell autoantibody
      (ICA) expression between 1994 and 2002. SETTING: The study was conducted in the
      general community. PARTICIPANTS: The Diabetes Prevention Trial-1 found 2817 ICA
      positive relatives who were tested for biochemical autoantibodies (GAD65, ICA512,
      and insulin) and HLA-DQ haplotypes, and 2796 of them were followed up for
      progression to diabetes for up to 8 yr (median, 3.6 yr). MAIN OUTCOME MEASURE:
      Progression to T1DM was measured. RESULTS: High-risk DQ haplotypes and genotypes
      were associated with a higher percentage of relatives expressing multiple
      biochemical autoantibodies and higher T1DM risk (e.g., respectively, 59 and 36%
      at 5 yr for carriers of the DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype).
      The number of autoantibodies expressed significantly increased T1DM risk and
      across different DQ genotypes, autoantibody positivity directly correlated with
      diabetes risk. However, multivariate analyses indicated that the influence of
      most genotypes on T1DM risk was not independent from autoantibody expression,
      with the possible exception of DQA1*0102-DQB1*0602. Specific genotypic
      combinations conferred 5-yr diabetes risks significantly lower (e.g. 7%-DQA1*0201
      DQB1*0201/DQA1*0501-DQB1*0201 and 14%-DQA1*0301-DQB1*0301/DQA1*0501-DQB1*0201)
      than when those haplotypes were found in other combinations. CONCLUSION: HLA DQ
      alleles determine autoantibody expression, which is correlated with diabetes
      progression. Among autoantibody-positive relatives, most HLA DQ genotypes did not
      further influence T1DM risk.

PMID- 16464955
TI  - Insulin resistance of muscle protein metabolism in aging.
AB  - A reduced response of older skeletal muscle to anabolic stimuli may contribute to
      the development of sarcopenia. We hypothesized that muscle proteins are resistant
      to the anabolic action of insulin in the elderly. We examined the effects of
      hyperinsulinemia on muscle protein metabolism in young (25+/-2 year) and older
      (68+/-1 year) healthy subjects using stable isotope tracer techniques. Leg blood
      flow was higher in the young at baseline and increased during hyperinsulinemia,
      whereas it did not change in the elderly. Glucose concentrations and muscle
      uptake were not different between groups at baseline and during hyperinsulinemia.
      Leg phenylalanine net balance was not different at baseline and significantly
      increased in both groups with hyperinsulinemia (P<0.05) but to a greater extent
      in the young (P<0.05). Muscle protein synthesis increased only in the young
      during hyperinsulinemia. Muscle protein breakdown did not significantly change in
      either group, although it tended to decrease in the elderly. Changes in muscle
      protein synthesis were correlated with changes in leg amino acid delivery
      (R=0.89; P=0.0001) and blood flow (R=0.90; P<0.0001). In conclusion, skeletal
      muscle protein synthesis is resistant to the anabolic action of insulin in older
      subjects, which may be an important contributor to the development of sarcopenia.

PMID- 16464957
TI  - Persistent and improved functional gain in mdx dystrophic mice after treatment
      with L-arginine and deflazacort.
AB  - Although an increase in nitric oxide (NO) in muscle is reported to improve the
      outcome of deflazacort treatment for mdx mouse muscular dystrophy, the genetic
      homologue of Duchenne muscular dystrophy (DMD), the impact such treatment on the
      functional outcomes of the disease, including fiber susceptibility to exercise
      induced injury, is not established. Experiments were designed to test whether
      treatment with deflazacort and L-arginine (a substrate for NO synthase, NOS)
      would change the extent of fiber injury induced by 24 h of voluntary exercise.
      The impact of exercise-related injury to induce a secondary regenerative response
      by muscle was also examined as corroborating evidence of muscle damage.
      Dystrophic mdx mice were treated for 3 wk with placebo, deflazacort, or
      deflazacort plus either L-arginine or N(G)-nitro-L-arginine methyl ester (a NOS
      inhibitor). Deflazacort, especially combined with L-arginine, spared quadriceps
      muscle from injury-induced regeneration (myf5 expression) compared with placebo
      treatment, despite an increase in membrane permeability immediately after
      exercise (assessed by Evans blue dye infiltration). Deflazacort alone prevented
      the typical progressive loss of function (measured as voluntary distance run over
      24 h) that was observed 3 months later in placebo-treated mice. Therefore,
      combined deflazacort plus L-arginine treatment spared mdx dystrophic limb muscle
      from exercise-induced damage and the need for regeneration and induced a
      persistent functional improvement in distance run. Results suggest a potential
      new treatment option for improving the quality of life for boys with DMD.

PMID- 16464956
TI  - HSP induction mediates selective clearance of tau phosphorylated at proline
      directed Ser/Thr sites but not KXGS (MARK) sites.
AB  - Neurofibrillary tangles (NFTs) are a characteristic neuropathological feature of
      Alzheimer's disease (AD), and molecular chaperones appear to be involved in the
      removal of disease-associated hyperphosphorylated tau, a primary component of
      NFTs. Here, novel HSP90 inhibitors were used to examine the impact of chaperone
      elevation on clearance of different tau species in transfected cells using a
      unique quantitative assay. The HSP90 inhibitors reduced levels of tau
      phosphorylated at proline-directed Ser/Thr sites (pS202/T205, pS396/S404) and
      conformationally altered (MC-1) tau species, an epitope that is immeasurable by
      standard Western blot techniques. The selective clearance of these phospho-tau
      species and MC-1 tau was mediated via the proteasome, while lysosomal-mediated
      tau degradation seems to lack specificity for certain tau species, suggesting a
      more general role in total tau removal. Interestingly, tau phosphorylated at
      S262/S356 within the tau microtubule binding domain was minimally affected by
      chaperone induction. Overall, our data show that chaperone induction results in
      the selective clearance of specific phospho-tau and conformationally altered tau
      species mediated by the proteasome; however, the apparent stability of pS262/S356
      tau may also explain why MARK is able to regulate normal tau function yet still
      be linked to the initiation of pathogenic tau hyperphosphorylation in AD.

PMID- 16464958
TI  - Innate immunity triggers oligodendrocyte progenitor reactivity and confines
      damages to brain injuries.
AB  - Regarded as a damaging reaction, innate immune response can either improve or
      worsen brain outcome after injury. Hence, inflammatory molecules might modulate
      cell susceptibility or healing events. The remyelination that follows brain
      lesions is dependent on the recruitment of oligodendrocyte progenitor cells
      (OPCs) and expression of genes controlling differentiation and myelin production,
      such as Olig1 and Olig2 bHLH transcription factors. We aimed to determine how
      innate immunity affects these processes. Here we report that lipopolysaccharide
      (LPS) infusion triggered OPC reactivity. Acute inflammation changed the
      distribution of Olig1- and Olig2-expressing cells following chemical
      demyelination, enhanced reappearance of transcription signals linked to
      remyelination and rapidly cleared myelin debris. Although cells expressing Olig1,
      Olig2, and proteolipid protein were attracted to demyelinated sites in the course
      of chronic inflammation, myelin loss was not associated with the effects of
      inflammation on OPC reactivity. In addition, the beneficial properties of brain
      immunity are broadened to an aggressive model of injury, wherein LPS through Toll
      like receptor 4 (TLR4) reduced surfactant-mediated damage while anti-inflammatory
      treatment enlarged the lesion. In conclusion, TLR4 activation in microglia is a
      powerful mechanism for improving repair at the remyelination level and protecting
      the cerebral tissue in presence of agents with strong cytolytic properties.

PMID- 16464959
TI  - Huntington disease patients and transgenic mice have similar pro-catabolic serum
      metabolite profiles.
AB  - There has been considerable progress recently towards developing therapeutic
      strategies for Huntington's disease (HD), with several compounds showing
      beneficial effects in transgenic mouse models. However, human trials in HD are
      difficult, costly and time-consuming due to the slow disease course, insidious
      onset and patient-to-patient variability. Identification of molecular biomarkers
      associated with disease progression will aid the development of effective
      therapies by allowing further validation of animal models and by providing
      hopefully more sensitive measures of disease progression. Here, we apply
      metabolic profiling by gas chromatography-time-of-flight-mass spectrometry to
      serum samples from human HD patients and a transgenic mouse model in a hypothesis
      generating search for disease biomarkers. We observed clear differences in
      metabolic profiles between transgenic mice and wild-type littermates, with a
      trend for similar differences in human patients and control subjects. Thus, the
      metabolites responsible for distinguishing transgenic mice also comprised a
      metabolic signature tentatively associated with the human disease. The candidate
      biomarkers composing this HD-associated metabolic signature in mouse and humans
      are indicative of a change to a pro-catabolic phenotype in early HD preceding
      symptom onset, with changes in various markers of fatty acid breakdown (including
      glycerol and malonate) and also in certain aliphatic amino acids. Our data raise
      the prospect of a robust molecular definition of progression of HD prior to
      symptom onset, and if validated in a genuinely prospective fashion these
      biomarker trajectories could facilitate the development of useful therapies for
      this disease.

PMID- 16464960
TI  - A low cost, colour coded, hand held spring scale accurately categorises birth
      weight in low resource settings.
AB  - AIMS: To determine the accuracy of a low cost, spring calibrated, hand held scale
      in classifying newborns into three weight categories (> or =2500 g, 2000-2499 g,
      <2000 g). METHODS: The test device was compared to a gold standard digital baby
      scale with precision to 2 g. In Sarlahi district, Nepal, 1890 newborns were
      eligible for the study. Measurements were collected for both the test device and
      the digital scale from 1820 (96.3%) newborns. RESULTS: The overall low birth
      weight (LBW) prevalence rate for the gold standard digital scale was 28.1%
      (511/1820). Sensitivity (93.7%) and specificity (97.6%) of the test device was
      high compared to LBW classifications based on digital weight measurements.
      Classification of infants into the <2000 g category was 5.0% and 4.7% for the
      gold standard and test device, respectively. Sensitivity and specificity of the
      test device in identifying infants <2000 g was 87.8% and 99.6%, respectively.
      Positive predictive values were high (>91%) for both weight categories
      CONCLUSIONS: This low cost, simple-to-use device classified infants into weight
      categories with a high degree of consistency and accuracy that exceeds that of
      surrogate measures. This new device is useful for identifying and targeting life
      saving interventions for LBW, high risk infants in settings where infants are
      born in the home and conventional weighing scales are unavailable.

PMID- 16464961
TI  - SIDS risk factors and factors associated with prone sleeping in Sweden.
AB  - OBJECTIVE: To compare the current prevalence of risk factors for sudden infant
      death syndrome (SIDS) in Sweden with a decade earlier, and assess factors
      associated with prone sleeping. METHODS: The results of a cohort study (Infants
      of Western Sweden) and a population based case-control study (Nordic
      Epidemiological SIDS Study) were examined. Subjects were 5600 healthy 6 month old
      infants born in 2003 in the Western Sweden region and 430 healthy Swedish infants
      born between 1991 and 1995. RESULTS: Prone sleeping decreased from 31.8% to 5.6%
      and supine sleeping increased from 35.3% to 47.3%. Side or side/supine sleeping
      increased from 25.2% to 43.8%. Maternal smoking during pregnancy decreased from
      23.5% to 9.5%. The risk for prone sleeping increased if the mother was unemployed
      (OR 2.4, 95% CI 1.5 to 4.0), if she was a heavy smoker in the third trimester (OR
      44.1, 95% CI 1.6 to 1199.6), and if the child was irritable (OR 2.5, 95% CI 1.3
      to 5.1), shared a bedroom with siblings (OR 2.6, 95% CI 1.0 to 6.6), or never
      used a dummy (OR 3.2, 95% CI 1.9 to 5.4). CONCLUSIONS: Parents have complied with
      advice to prevent SIDS given at infant welfare centres for the last 10 years. A
      change in the preferred sleeping position from side variants to exclusively
      supine, and reducing the number of pregnant women smoking may be beneficial. Use
      of a prone sleeping position was associated with maternal employment status,
      maternal smoking, temperament of the child, dummy use, and sharing a bedroom with
      siblings.

PMID- 16464962
TI  - Randomised controlled trial of combined paracetamol and ibuprofen for fever.
AB  - A randomised open label study of the combined use of paracetamol and ibuprofen to
      rapidly reduce fever is reported. The advantage of using both medications is less
      than half a degree centigrade in the first hour, and insufficient to warrant
      routine use.

PMID- 16464964
TI  - Respiratory infections in schoolchildren: co-morbidity and risk factors.
AB  - AIMS: To assess co-morbidity and risk factors for otitis media,
      tonsillopharyngitis, and lower respiratory infections in school children.
      METHODS: Logistic regression analysis of co-morbidity and risk factors for airway
      infections in a population based sample of 10 year old children living in Oslo,
      Norway. MAIN OUTCOME MEASURES: otitis media, tonsillopharyngitis, and lower
      respiratory infections in past 12 months. RESULTS: Airway infections in 10 year
      old children were common, and significant co-morbidity was found between the
      various airway infections. Home dampness was a risk factor for all infections,
      adjusted odds ratios ranging from 1.2 (95% CI 1.0 to 1.5) to 1.4 (95% CI 1.1 to
      1.6) for otitis media and tonsillopharyngitis respectively. Atopic disease was a
      constitutional risk factor, particularly strong for lower airway infections
      (adjusted odds ratio 2.4, 95% CI 1.8 to 3.1). African or Asian ethnicities were
      associated with the airway infections, adjusted odds ratios ranging from 1.2 (95%
      CI 0.9 to 1.7) to 1.7 (95% CI 1.2 to 2.3). CONCLUSIONS: Respiratory tract
      infections were common in 10 year old children. There was substantial co
      morbidity between upper and lower airway infections. Environmental and
      constitutional factors were identified and positively associated with the
      infections. Results support the hypothesis of 1957 that the whole respiratory
      tract is one unit.

PMID- 16464963
TI  - Temporal trend in paediatric infections in Denmark.
AB  - AIM: To study temporal trends in the incidence of hospitalisations due to
      infection in children in Denmark. METHODS: A national register based cohort of 1
      892 711 Danish children aged 0-5 years were studied from 1980 to 2001. Child and
      family characteristics were identified in the Danish Civil Registration System;
      hospitalisations were identified in the Danish National Patient Registry. Annual
      incidence rates were estimated using log-linear Poisson regression. RESULTS:
      During the studied period, the incidence of hospitalisations from infection
      increased by 62% in 0-5 year old children. The increase was mainly due to a
      sevenfold increase in the incidence of infections leading to short term
      hospitalisation in children aged 0-1 years. Since the increase in incidence was
      contrasted with a decrease in duration of hospitalisation, no further strain was
      put on the health services in Denmark. CONCLUSION: During the last two decades,
      the incidence of short term hospitalisations due to infections increased markedly
      among the youngest children. However, the strain on the health services remained
      constant. The observed increase in the incidence of short term hospitalisations
      among the youngest children may reflect changes in hospitalisation practices and
      utilisation, rather than an increase in incidence of infections.

PMID- 16464965
TI  - Transport is not rate-limiting in morphine glucuronidation in the single-pass
      perfused rat liver preparation.
AB  - Binding, transport, and metabolism are factors that influence morphine (M)
      removal in the rat liver. For M and the morphine 3beta-glucuronide metabolite
      (M3G), modest binding existed with 4% bovine serum albumin (unbound fractions of
      0.89 +/- 0.07 and 0.98 +/- 0.09, respectively), and there was partitioning of M
      into red blood cells. Transport studies of M (<750 microM) showed similar,
      concentration-independent uptake clearances (CLs) of 1.5 ml min(-1) g(-1) among
      zonal and homogeneous, isolated rat hepatocytes. Transport of M3G, ascertained in
      multiple indicator dilution studies at various steady-state M3G concentrations
      (10-262 microM), uncovered a low and concentration-independent influx clearance
      (<10% of flow rate). The outflow dilution curve of [(3)H]M3G was superimposable
      onto that of [(14)C]sucrose, the extracellular reference, displaying similarity
      in transit times (23.5 and 22.2 s), negligible biliary excretion, and almost
      complete dose recovery from perfusate. In contrast, M3G occurred abundantly in
      both perfusate and bile in single-pass perfusion studies of the precursor, M, and
      revealed a biliary clearance of formed M3G that was 12.3-fold that of preformed
      M3G, suggesting a sinusoidal, diffusional barrier for M3G. With increasing
      concentrations of M (9-474 microM), clearance decreased, and metabolism and
      biliary excretion displayed concentration-dependent kinetics. Fitting of the data
      to a physiologically based liver model revealed that M removal mechanisms were
      saturable, with a K(m,met) of 52.2 microM and V(max,met) of 58.8 nmol min(-1) g(
      1) for metabolism, and a K(m,ex) of 41.2 microM and V(max,ex) of 8.1 nmol min(-1)
      g(-1) for excretion. Sinusoidal transport was not rate-limiting for M removal.

PMID- 16464966
TI  - Lipopolysaccharide induces epithelium- and prostaglandin E(2)-dependent
      relaxation of mouse isolated trachea through activation of cyclooxygenase (COX)-1
      and COX-2.
AB  - Lipopolysaccharide (LPS), a Toll-like receptor (TLR) 4 agonist, causes airway
      hyperreactivity through nuclear factor-kappaB (NF-kappaB). Because NF-kappaB
      induces cyclooxygenase-2 (COX-2) to increase synthesis of prostaglandins (PGs),
      including the potent airway anti-inflammatory and smooth muscle relaxant PGE(2),
      we investigated whether LPS causes short-term PGE(2)-dependent relaxation of
      mouse isolated trachea. In rings of trachea contracted submaximally with
      carbachol, LPS caused slowly developing, epithelium-dependent relaxations that
      reached a maximum within 60 min. Fluorescence immunohistochemistry revealed TLR4
      like immunoreactivity localized predominantly to the epithelium. The LPS
      antagonist polymixin B; the nonselective COX inhibitor indomethacin; the
      selective COX-1 and COX-2 inhibitors 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3
      (trifluoromethyl)-1H-pyrazole (SC560) and 4-[5-(4-chlorophenyl)-1
      (trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide (SC236), respectively; the
      transcription inhibitor actinomycin D; the translation inhibitor cycloheximide;
      the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor 4-(4-fluorophenyl)
      2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imadazole (SB203580); and a
      combination of the mixed DP/EP1/EP2 receptor antagonist 6-isopropoxy-9-xanthone-2
      carboxylic acid (AH6809) and the EP4 receptor antagonist 4'-[3-butyl-5-oxo-1-(2
      trifluoromethyl-phenyl)-1-5-dihydro-[1,2,4]triazol-4-ylmethyl]-biphenyl-2
      sulfonic acid (3-methyl-thiophene-2-carbonyl)-amide (L-161982) all abolished
      relaxation to LPS, giving instead slowly developing, small contractions over 60
      min. The cytosolic phospholipase A(2) (cPLA(2)) inhibitor 1,1,1-trifluoro-6Z,9Z,
      12Z,15Z-heneicosateraen-2-one significantly (p < 0.05) inhibited the relaxation
      to LPS, whereas the NF-kappaB proteasomal inhibitor Z-Leu-Leu-Leu-aldehyde (MG
      132) had no affect on the relaxation in the first 20 min, after which it reversed
      the response to a contraction. In conclusion, our data indicate that LPS
      activates airway epithelial TLR4 to cause release of PGE(2) and subsequent EP2
      and EP4 receptor-dependent smooth muscle relaxation. Activation of both COX-1 and
      COX-2 seems to be essential for this novel response to LPS, which also involves
      cPLA(2), p38 MAPK, NF-kappaB, and an unidentified NF-kappaB-independent, labile
      regulatory protein.

PMID- 16464967
TI  - Capacity of ocular infiltrating T helper type 1 cells of patients with non
      infectious uveitis to produce chemokines.
AB  - BACKGROUND/AIMS: Chemokines are key molecules that initiate leucocyte
      infiltration to the inflammatory site. The involvement of chemokines in uveitis
      is well studied, yet the source of this molecule in the inflamed eye is not
      clearly identified. The possible sources of chemokines are ocular resident cells
      or the inflammatory cells infiltrated to the eye. Here the authors examined
      whether ocular infiltrating T cells of uveitis patients do produce chemokines.
      METHODS: T cell clones (TCCs) were established from ocular infiltrating cells of
      patients with non-infectious uveitis. TCCs were characterised using flow
      cytometry. Spontaneous production of chemokines by TCCs was evaluated by ELISA.
      RESULTS: TCCs from ocular infiltrating cells were revealed to be memory activated
      Th1 type CD4 positive cells. Those TCCs produced larger amounts of chemokines
      than TCCs from peripheral blood mononuclear cells of uveitis or healthy donors.
      CONCLUSIONS: The present data indicate that ocular infiltrating T cells of
      patients with non-infectious uveitis produce chemokines and recruit further
      infiltrating lymphoid cells. Such T cells may have roles in the prolonged/chronic
      state of non-infectious uveitis.

PMID- 16464968
TI  - Integrity of foveal cones in multiple evanescent white dot syndrome assessed with
      OCT and foveal reflection analyser.

PMID- 16464969
TI  - Human glaucoma and neural degeneration in intracranial optic nerve, lateral
      geniculate nucleus, and visual cortex.
AB  - The pathology of glaucoma has been extensively studied at the level of the retina
      and optic nerve head. Here the first clinicopathological case of human glaucoma
      is reported demonstrating degenerative changes in the brain involving the
      intracranial optic nerve, lateral geniculate nucleus, and visual cortex.
      Pathological evidence of neural degeneration in this patient is correlated with
      clinical, optic nerve head, visual field, and neuroradiology findings.
      Neuropathology in the glaucoma brain is compared to age matched controls. In the
      presence of advanced human glaucoma with 50% visual field loss, neural damage is
      evident in multiple vision stations within the brain.

PMID- 16464970
TI  - Optical coherence tomography to monitor photodynamic therapy in pathological
      myopia.
AB  - AIM: To evaluate the role of optical coherence tomography (OCT) in determining
      choroidal neovascularisation (CNV) activity before and after photodynamic therapy
      (PDT) in patients with pathological myopia. METHODS: 33 patients (33 eyes) with
      pathological myopia and being treated with PDT were included. Every 3 months all
      patients were evaluated and presence or absence of leakage on fluorescein
      angiography, presence of intraretinal or subretinal fluid on OCT, and macular and
      choroidal neovascular complex thickness on OCT, were determined at each
      examination. RESULTS: The macular thickness decreased significantly after PDT at
      6 months (p = 0.001) and at 12 months follow up (p = 0.01). However, no
      significant changes in CNV thickness were measured after PDT at 6 months of
      follow up (p = 0.418) and at 12 months of follow up (p = 0.521). Once the
      diagnosis of CNV associated with pathological myopia was established, before
      treatment, OCT had a sensitivity of 96.96% for detecting CNV activity. After
      treatment, OCT had a good sensitivity (95.23%) and a moderate specificity
      (69,69%) in determining CNV activity, which resulted in a diagnostic efficiency
      (proportion of correct results) of 79.62%. CONCLUSIONS: OCT appears to be useful
      for indicating CNV activity. Therefore, it may serve as a complementary technique
      for deciding the need for PDT and re-treatment in patients with pathological
      myopia.

PMID- 16464971
TI  - The temporal retinal vessel angle and infants born preterm.
AB  - AIM: To determine the temporal retinal vessel angle in babies and its relation to
      preterm birth. METHODS: Digital images were obtained during routine screening for
      retinopathy of prematurity (ROP). The temporal retinal vessel angle was measured
      in 164 eyes of 82 babies born "very preterm" (24-27 weeks gestational age (GA)),
      "preterm" (28-31 weeks GA), and "near term" (>/=32 weeks GA). RESULTS: Mean
      temporal vessel angle (TVA) for all three GA groups together is 80.0 degrees (SD
      17.0 degrees ) for the right eye and 80.5 degrees (16.7 degrees ) for the left
      eye. The range is right eye 59-106 degrees , left eye 69-97 degrees , with 95%
      data above 67 degrees for the right and 63 degrees for the left eye. For babies
      born near term, TVA is 82 degrees in each eye. There is a high degree of
      interocular symmetry between right and left eyes and a statistically
      insignificant trend for increasing TVA with increasing GA. The presence and stage
      of ROP affected one parameter of the left eye alone. CONCLUSIONS: These data
      provide normative data on the TVA in babies and will facilitate, especially if
      there is interocular asymmetry, determining whether there is macular
      displacement.

PMID- 16464972
TI  - Selective laser trabeculoplasty: predictive value of early intraocular pressure
      measurements for success at 3 months.
AB  - AIM: To determine the predictive value of the 2 week post-selective laser
      trabeculoplasty (SLT) intraocular pressure (IOP) by comparing it to the 4 week
      and 3 month values. METHODS: A retrospective chart review of eyes that underwent
      SLT between 2001 and 2004 was performed. The primary outcome measure was IOP.
      Demographic and medical data were collected for correlational analysis. RESULTS:
      132 eyes of 95 patients were identified, none was excluded. Of the eyes that
      exhibited a decrease in IOP of >1 mm Hg at 2 weeks postoperatively, 99.24%
      continued to show a lowered IOP at the 4 week and 3 month visits. For these
      patients, the Pearson's r value between 2 weeks and 4 weeks was 0.708 (p value =
      0.01) while the r value between 2 weeks and 3 months was 0.513 (p value = 0.01).
      CONCLUSIONS: The 2 week visit post-SLT predicted the 4 week and 3 month visits if
      the 2 week visit demonstrated a decrease in IOP. These findings suggest that
      those patients who had a decreased IOP at 2 weeks and are at their goal IOP may
      not need to be screened until 3 months postoperatively.

PMID- 16464973
TI  - Detection of differential gene expression in brown adipose tissue of hibernating
      arctic ground squirrels with mouse microarrays.
AB  - Hibernation is an energy-saving strategy adopted by a wide range of mammals to
      survive highly seasonal or unpredictable environments. Arctic ground squirrels
      living in Alaska provide an extreme example, with 6- to 9-mo-long hibernation
      seasons when body temperature alternates between levels near 0 degrees C during
      torpor and 37 degrees C during arousal episodes. Heat production during
      hibernation is provided, in part, by nonshivering thermogenesis that occurs in
      large deposits of brown adipose tissue (BAT). BAT is active at tissue
      temperatures from 0 to 37 degrees C during rewarming and continuously at near 0
      degrees C during torpor in subfreezing conditions. Despite its crucial role in
      hibernation, the global gene expression patterns in BAT during hibernation
      compared with the nonhibernation season remain largely unknown. We report a large
      scale study of differential gene expression in BAT between winter hibernating and
      summer active arctic ground squirrels using mouse microarrays. Selected
      differentially expressed genes identified on the arrays were validated by
      quantitative real-time PCR using ground squirrel specific primers. Our results
      show that the mRNA levels of the genes involved in nearly every step of the
      biochemical pathway leading to nonshivering thermogenesis are significantly
      increased in BAT during hibernation, whereas those of genes involved in protein
      biosynthesis are significantly decreased compared with summer active animals in
      August. Surprisingly, the differentially expressed genes also include adipocyte
      differentiation-related protein or adipophilin (Adfp), gap junction protein 1
      (Gja1), and secreted protein acidic and cysteine-rich (Sparc), which may play a
      role in enhancing thermogenesis at low tissue temperatures in BAT.

PMID- 16464974
TI  - Role of endothelial cell apoptosis in regulation of skeletal muscle angiogenesis
      during high and low salt intake.
AB  - Angiogenesis, under normal conditions, is a tightly regulated balance between pro
      and antiangiogenic factors. The goal of this study was to investigate the
      mechanisms involved in the control of the skeletal muscle angiogenic response
      induced by electrical stimulation during the suppression of plasma renin activity
      (PRA) with a high-salt diet. Rats fed 0.4% or 4% salt diets were exposed to
      electrical stimulation for 7 days. The tibialis anterior (TA) muscles from
      stimulated and unstimulated hindlimbs were removed and prepared for gene
      expression analysis, CD31-terminal deoxynucleotide transferase-mediated dUTP nick
      end labeling (TUNEL) double-staining assay, and Bcl-2 and Bax protein expression
      by Western blot. Rats fed a low-salt diet showed a dramatic angiogenesis response
      in the stimulated limb compared with the unstimulated limb. This angiogenesis
      response was significantly attenuated when rats were placed on a high-salt diet.
      Microarray analysis showed that in the stimulated limb of rats fed a low-salt
      diet many genes related to angiogenesis were upregulated. In contrast, in rats
      fed a high-salt diet most of the genes upregulated in the stimulated limb
      function in apoptosis and cell cycle arrest. Endothelial cell apoptosis, as
      analyzed by CD31-TUNEL staining, increased by fourfold in the stimulated limb
      compared with the unstimulated limb. There was also a 48% decrease in the Bcl-2
      to-Bax ratio in stimulated compared with unstimulated limbs of rats fed a high
      salt diet, confirming severe apoptosis. This study suggests that the increase in
      endothelial cell apoptosis in TA muscle might contribute to the attenuation of
      angiogenesis response observed in rats fed a high-salt diet.

PMID- 16464975
TI  - Functional mapping for genetic control of programmed cell death.
AB  - "Naturally occurring" or "programmed" cell death (PCD) in which the cell uses
      specialized cellular machinery to kill itself is a ubiquitous phenomenon that
      occurs early in organ development. Such a cell suicide mechanism that enables
      metazoans to control cell number and eliminate cells threatening the organism's
      survival has been thought to be under genetic control. In this report, we develop
      a novel statistical model for mapping specific genes or quantitative trait loci
      (QTL) that are responsible for the PCD process based on polymorphic molecular
      markers. This model incorporates the biological mechanisms of PCD that undergoes
      two different developmental stages, exponential growth and polynomial death. We
      derived a parametric approach to model the exponential growth and a nonparametric
      approach based on the Legendre function to model the polynomial death. A series
      of stationary and nonstationary models has been used to approximate the structure
      of the covariance matrix among cell numbers at a multitude of different times.
      The statistical behavior of our model is investigated through simulation studies
      and validated by a real example in rice.

PMID- 16464977
TI  - Implementation and evaluation of a neonatal educational program in rural Nepal.
AB  - A needs assessment at Tansen Mission Hospital established gaps in knowledge,
      skills and attitudes of health professionals, contributing to the high neonatal
      mortality in Nepal. This study was designed to implement and evaluate the
      effectiveness of an educational program in Newborn Care, using best evidence
      teaching methods and content. Pre intervention, an audit of newborn care
      practices and documentation was performed using a structured checklist.
      Intervention consisted of four teaching sessions each involving short lectures
      and interactive skills stations. Post intervention, participant satisfaction,
      knowledge, competence and performance were evaluated. In 80 per cent of responses
      (n=30), participants evaluated the program as very good or excellent. Matched
      pair pre and post education MCQ scores compared knowledge, with significant
      improvement in all groups (nurses, doctors and community health workers).
      Competence was evaluated by an Objective Structured Clinical Examination with
      mean scores (+/-SD) ranging from 65 per cent (7.0) to 87 per cent (7.3).
      Performance was examined by pre and post-intervention audit of records.
      Significant changes in practice included a 100 per cent increase in measuring
      length and head circumference, charting percentiles and documentation of
      structured history and examination in the Newborn Care Notes. Administration of
      vitamin K at birth increased by 71 per cent, assessment of hypoglycaemia risk by
      94 per cent and those at risk of hypoglycaemia having a blood sugar level
      measured increased by 58 per cent. These results led to consideration of
      appointment of a postgraduate educator. Even with limitations in educating and
      implementing change in a resource limited rural setting, a short, interactive
      education program can have positive educational outcomes and can change practice.
      Sustainability is dependent on staff employing continuing education.

PMID- 16464976
TI  - Gene expression in human small intestinal mucosa in vivo is mediated by iron
      induced oxidative stress.
AB  - Iron-induced oxidative stress in the small intestine may alter gene expression in
      the intestinal mucosa. The present study aimed to determine which genes are
      mediated by an iron-induced oxidative challenge in the human small intestine.
      Eight healthy volunteers [22 yr(SD2)] were tested on two separate occasions in a
      randomized crossover design. After duodenal tissue sampling by
      gastroduodenoscopy, a perfusion catheter was inserted orogastrically to perfuse a
      40-cm segment of the proximal small intestine with saline and, subsequently, with
      either 80 or 400 mg of iron as ferrous gluconate. After the intestinal perfusion,
      a second duodenal tissue sample was obtained. Thiobarbituric acid-reactive
      substances, an indicator of lipid peroxidation, in intestinal fluid samples
      increased significantly and dose dependently at 30 min after the start of
      perfusion with 80 or 400 mg of iron, respectively (P < 0.001). During the
      perfusion with 400 mg of iron, the increase in thiobarbituric acid-reactive
      substances was accompanied by a significant, momentary rise in trolox equivalent
      antioxidant capacity, an indicator of total antioxidant capacity (P < 0.05). The
      expression of 89 gene reporters was significantly altered by both iron
      interventions. Functional mapping showed that both iron dosages mediated six
      distinct processes. Three of those processes involved G-protein receptor coupled
      pathways. The other processes were associated with cell cycle, complement
      activation, and calcium channels. Iron administration in the small intestine
      induced dose-dependent lipid peroxidation and a momentary antioxidant response in
      the lumen, mediated the expression of at least 89 individual gene reporters, and
      affected at least six biological processes.

PMID- 16464979
TI  - A comparison of patient-controlled subacromial and i.v. analgesia after open
      acromioplasty surgery.
AB  - BACKGROUND: The aim of this study was to compare three patient-controlled
      analgesia (PCA) techniques for pain relief after acromioplasty. These techniques
      included use of subacromial ropivacaine, subacromial fentanyl or i.v. fentanyl.
      METHODS: Forty-eight patients scheduled for open acromioplasty surgery were
      prospectively randomized to receive ropivacaine 0.2% (Group R) or fentanyl 4
      microg ml(-1) (Group F) for subacromial analgesia, or fentanyl 4 microg ml(-1)
      (Group C) for i.v. analgesia. All patients received background infusion at a rate
      of 5 ml h(-1) plus a PCA bolus dose of 3 ml with a lockout time of 20 min. In
      addition, rescue analgesia with tramadol 50-100 mg i.v. was available on demand.
      Pain relief was regularly assessed using a visual analogue scale (0-10 cm) and
      side-effects were noted. RESULTS: The postoperative pain scores at 2, 4, 6 and 12
      h after the start of PCA were higher in Group F compared with Group R and Group C
      (P<0.001), However, the pain scores at the other time points were similar between
      the three groups. Pain scores, incremental dose requested and received, total
      volume of analgesic solution infused and rescue tramadol were similar between
      Group R and Group C. Specific side-effects were similar in the three groups.
      CONCLUSION: The PCA techniques using subacromial ropivacaine or fentanyl i.v.
      provided similar and adequate pain relief and minimal side-effects after open
      acromioplasty surgery. The PCA using subacromial fentanyl was not as effective as
      either subacromial ropivacaine or i.v. fentanyl.

PMID- 16464978
TI  - Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood
      coagulation.
AB  - BACKGROUND: Development of hydroxyethyl starches (HES) with a low impact on blood
      coagulation but a long intravascular persistence is of clinical interest. A
      previous in vitro study showed that low substituted high molecular weight HES
      does not compromise blood coagulation more than medium molecular weight HES. In
      the present study we assessed the individual effects on blood coagulation of
      molar substitution and C2/C6 ratio of a high molecular weight HES. METHODS: Blood
      was obtained from 30 healthy patients undergoing elective surgery and mixed with
      six high molecular weight (700 kDa) HES solutions differing in their molar
      substitution (0.42 and 0.51) and C2/C6 ratio (2.7, 7 and 14) to achieve 20, 40
      and 60% dilution. Blood coagulation was assessed by Thrombelastograph analysis
      (TEG) and plasma coagulation tests. Data were compared using a three-way analysis
      of variance model with repeated measures on the three factors. RESULTS: Higher
      molar substitution compromised blood coagulation most (for all TEG parameters,
      P<0.05). The lowest C2/C6 ratio was associated with the lowest effect on blood
      coagulation; r (P<0.001), angle alpha (P=0.003) and coagulation index (P<0.001).
      No effect on k and maximum amplitude was observed (P for both >0.50). The higher
      molar substitution was associated with a lesser increase in PT (P=0.007) and a
      greater decrease in factor VIII (P=0.010). PTT, functional and antigenic von
      Willebrand factors were not significantly influenced by molar substitution (P for
      all >0.20). No significant differences between solutions with the same molar
      substitution but different C2/C6 ratios were found in plasma coagulation
      parameters (P for all >0.05). CONCLUSIONS: TEG analysis indicates that high
      molecular HES with a molar substitution of 0.42 and a C2/C6 ratio of 2.7 has the
      lowest effect on in vitro human blood coagulation.

PMID- 16464980
TI  - Neurosurgical operations with the patient in sitting position: analysis of risk
      factors using transcranial Doppler sonography.
AB  - BACKGROUND: One major risk factor of the sitting position for neurosurgery is air
      embolism, especially in patients with persistent foramen ovale (PFO). The first
      aim of this prospective study was to evaluate a bedside method for detecting PFO
      using transcranial Doppler sonography (TCD) with contrast medium. A second aim
      was to address intraoperative monitoring, patient positioning and the occurrence
      and clinical relevance of air embolism. METHODS: Ninety patients with a mean age
      of 56.5 yr (range 14-81 yr) undergoing surgery in sitting position were
      investigated by TCD with contrast agent to detect functional PFO, that is PFO
      that can be provoked with a Valsalva manoeuvre. In patients in whom TCD was not
      possible, transcranial duplex sonography, duplex sonography of the carotid artery
      at the neck or transoesophageal ECG was performed. RESULTS: In 26 patients PFO
      was detected. Thirteen of them presented a persistent PFO with high-intensity
      transient signal in both middle cerebral arteries without Valsalva manoeuvre. The
      intraoperative positioning in these patients was adapted to the risk for a
      paradoxical air embolism, although, after surgical recommendations, three
      patients with a persistent PFO underwent surgery in sitting position.
      Intraoperative air embolisms were seen in 8 of 80 patients in sitting or semi
      sitting position with air aspirable through the central venous catheter.
      CONCLUSION: To address the risk of a paradoxical air embolism, especially in
      patients undergoing surgery in sitting position, preoperative detection of PFO is
      advisable. If surgery is performed in seated PFO patients, additional monitoring
      and special care are warranted.

PMID- 16464981
TI  - Tracheal tube-tip displacement in children during head-neck movement--a
      radiological assessment.
AB  - BACKGROUND: Aims of this study were to assess the maximum displacement of
      tracheal tube tip during head-neck movement in children, and to evaluate the
      appropriateness of the intubation depth marks on the Microcuff Paediatric
      Endotracheal Tube regarding the risk of inadvertent extubation and endobronchial
      intubation. METHODS: We studied children, aged from birth to adolescence,
      undergoing cardiac catheterization. The patients' tracheas were orally intubated
      and the tracheal tubes positioned with the intubation depth mark at the level of
      the vocal cords. The tracheal tube tip-to-carina distances were fluoroscopically
      assessed with the patient supine and the head-neck in 30 degrees flexion, 0
      degrees neutral position and 30 degrees extension. RESULTS: One hundred children
      aged between 0.02 and 16.4 yr (median 5.1 yr) were studied. Maximum tracheal tube
      tip displacement after head-neck 30 degrees extension and 30 degrees flexion
      demonstrated a linear relationship to age [maximal upward tube movement (mm)=0
      0.71 x age (yr)+9.9 (R(2)=0.893); maximal downward tube movement (mm)=0.83 x age
      (yr)+9.3 (R(2)=0.949)]. Maximal tracheal tube-tip downward displacement because
      of head-neck flexion was more pronounced than upward displacement because of head
      neck extension. CONCLUSIONS: The intubation depth marks were appropriate to avoid
      inadvertent tracheal extubation and endobronchial intubation during head-neck
      movement in all patients. However, during head-neck extension the tracheal tube
      cuff may become positioned in the subglottic region and should be re-adjusted
      when the patient remains in this position for a longer time.

PMID- 16464982
TI  - Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in
      the anaesthetized Rhesus monkey.
AB  - BACKGROUND: Binding of the steroidal molecule of rocuronium by a cyclodextrin is
      a new concept for reversal of neuromuscular block. The present study evaluated
      the ability of Sugammadex Org 25969, a synthetic gamma-cyclodextrin derivative,
      to reverse constant neuromuscular block of about 90% induced by rocuronium or the
      non-steroidal neuromuscular blocking drugs, mivacurium or atracurium, in the
      anaesthetized Rhesus monkey. METHODS: After a bolus injection of rocuronium,
      mivacurium or atracurium, a continuous infusion of these drugs was started to
      maintain the first twitch contraction of the train-of-four at approximately 10%
      of its baseline value. After a steady state block of at least 10 min the infusion
      was stopped and the preparation was allowed to recover spontaneously. This
      process was repeated, but at the time the infusion was stopped, either sugammadex
      0.5 or 1.0 mg kg(-1) was given in the rocuronium-induced blockade and sugammadex
      1.0 mg kg(-1) was given in the mivacurium- and atracurium-induced blockade.
      RESULTS: Sugammadex caused a rapid and complete reversal of rocuronium-induced
      neuromuscular block. The recovery time to train of four ratio=0.9 after
      spontaneous recovery was 14.4 min (sd=3.4 min; n=14). This was reduced
      significantly (P<0.001) to 3.7 min (sd=3.3 min; n=4) with sugammadex 0.5 mg kg(
      1) and to 1.9 min (sd=1.0 min; n=4) with sugammadex 1.0 mg kg(-1). Signs of
      residual blockade or re-curarization were not observed. Reversal of mivacurium-
      or atracurium-induced neuromuscular block (n=2 in each experiment) by sugammadex
      (1.0 mg kg(-1)) was not effective. In all experiments, injection of sugammadex
      had no effects on blood pressure or heart rate. CONCLUSIONS: Sugammadex is
      effective in reversing rocuronium, but not mivacurium- or atracurium-induced
      neuromuscular block.

PMID- 16464983
TI  - Severe epilepsy resulting from genetic interaction between Scn2a and Kcnq2.
AB  - A mutation in the voltage-gated sodium-channel Scn2a results in moderate epilepsy
      in transgenic Scn2a(Q54) mice maintained on a C57BL/6J strain background. The
      onset of progressive epilepsy begins in adults with short-duration partial
      seizures that originate in the hippocampus. The underlying abnormality is an
      increase in persistent sodium current in hippocampal neurons. The voltage-gated
      potassium channel Kcnq2 is responsible for generating M current (I(KM)) that is
      thought to control excitability and limit repetitive firing of hippocampal
      neurons. To determine whether impaired M current would exacerbate the seizure
      phenotype of Scn2a(Q54) mice, we carried out genetic crosses with two mutant
      alleles of Kcnq2. Szt1 mice carry a spontaneous deletion that removes the C
      terminal domain of Kcnq2. A novel Kcnq2 missense mutation V182M was identified by
      screening the offspring of ENU-treated males for reduced threshold to
      electrically evoked minimal clonic seizures. Double mutant mice carrying the
      Scn2a(Q54) transgene together with either of the Kcnq2 mutations exhibited severe
      epilepsy with early onset, generalized tonic-clonic seizures and juvenile
      lethality by 3 weeks of age. This dramatic exacerbation of the sodium-channel
      mutant phenotype indicates that M current plays a critical role in preventing
      seizure initiation and spreading in this animal model. The genetic interaction
      between Scn2a and Kcnq2 demonstrates that combinations of mild alleles of
      monogenic epilepsy genes can result in severe disease and provides a model for
      complex inheritance of human epilepsy. The data suggest that interaction between
      these genes might contribute to the variable expressivity observed in human
      families with sodium-channel mutations. In a screen of 23 SMEI patients with
      missense mutations of SCN1A, no second-site mutations in KCNQ2 were identified.

PMID- 16464984
TI  - An international study on starting tumour necrosis factor-blocking agents in
      ankylosing spondylitis.
AB  - OBJECTIVES: To determine the type and proportion of patients with ankylosing
      spondylitis who rheumatologists consider to be candidates for treatment with
      tumour necrosis factor (TNF)-blocking agents, and to what extent this is in
      agreement with the ASsessment in Ankylosing Spondylitis (ASAS) international
      working group recommendations on initiation of treatment with anti-TNF agents.
      METHODS: Participants were rheumatologists from 10 different countries, who were
      considered to be experts in treating patients with ankylosing spondylitis and in
      the use of anti-TNF treatment, but were unaware of the ASAS recommendations
      (unpublished at the time of study in 2003). The first 10 consecutive patients
      with ankylosing spondylitis seen by the rheumatologist were evaluated as to
      whether the patient was a candidate for anti-TNF treatment. Thereafter, a
      metrologist assessed the patient for disease activity and severity, and collected
      data on demographics and treatment. RESULTS: Complete data were available for
      1207 of the 1284 patients and were used for analysis. Overall, the
      rheumatologists indicated that they would initiate TNF-blocking agents in 49.3%
      of patients, ranging from 37.2% patients in Canada to 78.3% in Australia. These
      candidates had higher disease activity, higher levels of acute-phase reactants,
      worse spinal mobility, worse function, more often hip involvement and a higher
      prevalence of sick leave. Of all patients considered to be candidates, 40% did
      not fulfil ASAS recommendations with respect to previous use of non-steroidal
      anti-inflammatory drugs (NSAIDs; at least two NSAIDs) or Bath Ankylosing
      Spondylitis Disease Activity Index (>or=4). Conversely, 36% of patients who did
      not fulfil the NSAID or BASDAI recommendations were still considered to be
      candidates for TNF-blocking treatment. OBJECTIVE: variables, such as C reactive
      protein, erythrocyte sedimentation rate or magnetic resonance activity, were
      considered less important than disease activity in the decision on starting TNF
      blocking drugs. The only important objective criterion was rapid radiographic
      progression. CONCLUSION: Rheumatologists wanted to initiate TNF-blocking drugs in
      roughly half of the patients with ankylosing spondylitis. However, there was a
      wide variation across countries and doctors. Rheumatologists considered both
      disease activity and severity to be determinants of starting TNF blockers, but
      their decision was often in disagreement with ASAS recommendations.

PMID- 16464985
TI  - Balloon angioplasty of arteries of the upper extremities in patients with
      extracranial giant-cell arteritis.
AB  - OBJECTIVES: To evaluate the outcome of balloon angioplasty in the arteries of the
      upper extremities in patients with giant-cell arteritis (GCA) and stenosing
      extracranial involvement. METHODS: Percutaneous transluminal angioplasty (PTA)
      for symptomatic upper limb artery stenoses (n = 29) and occlusions (n = 1)
      resistant to medical treatment was carried out in 10 patients (all women, mean
      age 65 years) with GCA. Vascular lesions were located in the subclavian (n = 4),
      axillary (n = 10) and brachial (n = 16) arteries. Interventional treatment was
      accompanied by immunosuppressive drugs in all patients. Follow-up included
      clinical and serological examination, magnetic resonance angiography and colour
      duplex ultrasound. RESULTS: Initial technical success of angioplasty was achieved
      in the case of all vascular lesions. In five patients, marked recurrent stenoses
      (vascular territories; n = 10/30) were found during follow-up (mean 24 months).
      The cumulative primary patency rate was 65.2%. All recurrent lesions developed in
      the territories of the initial long-segment stenoses. Repeated PTA (vascular
      territories, n = 8; patients, n = 5) provided a cumulative secondary patency rate
      of 82.6% and a cumulative tertiary patency rate of 89.7%. CONCLUSIONS: Despite a
      tendency to restenoses, balloon angioplasty of the upper-extremity artery, in
      combination with immunosuppressive treatment, is an efficient method for the
      treatment of extracranial GCA.

PMID- 16464986
TI  - Lack of association between the protein tyrosine phosphatase non-receptor 22
      (PTPN22)*620W allele and systemic sclerosis in the French Caucasian population.
AB  - The minor allele of the R620W missense single-nucleotide polymorphism (SNP;
      rs2476601) in the PTPN22 (protein tyrosine phosphatase non-receptor 22) gene has
      been reported to be associated with multiple autoimmune diseases, including type
      1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, juvenile
      idiopathic arthritis, autoimmune thyroiditis and vitiligo. Systemic sclerosis
      (SSc) is a connective tissue disease with some autoimmune abnormalities. The aim
      of our study was to test for association of the PTPN22*620W allele with SSc in a
      French Caucasian cohort with a case-control study of 121 patients with SSc and
      103 controls. All patients and controls were genotyped for the PTPN22*R620W SNP.
      No association was found between the PTPN22*620W allele and SSc (7% v 9.2%, p =
      0.39). The frequency of genotypes carrying at least one 620W allele was similar
      in both groups (13% v 17%, p = 0.38). The PTPN22*620W allele was also not
      associated with autoantibody patterns. Thus, the PTPN22*R620W polymorphism cannot
      be regarded as a genetic susceptibility factor for SSc in the French Caucasian
      population.

PMID- 16464987
TI  - Definition of disease duration in ankylosing spondylitis: reassessing the
      concept.
AB  - The concept and definition of disease duration in patients with ankylosing
      spondylitis is ambiguous, and often many years pass between the onset of symptoms
      and diagnosis. Members of the Assessment in Ankylosing Spondylitis (ASAS)
      International Working Group by consensus recently recommended identifying
      specific components of the medical history to better define and document the
      concept of disease duration. These include (1) the time of onset of the first
      symptoms of axial manifestations (including inflammatory back pain); (2) the time
      of onset of the first symptoms of each individual manifestation, which may be an
      extra-axial sign or symptom of ankylosing spondylitis, such as peripheral
      arthritis and enthesitis; (3) the time of onset of associated diseases belonging
      to the spondyloarthritides, in particular acute anterior uveitis, inflammatory
      bowel disease and psoriasis; and (4) the time since actual diagnosis by a
      healthcare provider. Such uniformity in data collection will ensure comparability
      across studies and facilitate future research.

PMID- 16464988
TI  - Efficacy and safety of combination etanercept and methotrexate versus etanercept
      alone in patients with rheumatoid arthritis with an inadequate response to
      methotrexate: the ADORE study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of etanercept (ETN) monotherapy
      compared with combination ETN and methotrexate (MTX) treatment in patients with
      rheumatoid arthritis who had an inadequate response to MTX monotherapy. (The
      response was defined by the presence of Disease Activity Score-28 joint count
      (DAS28) >or=3.2 or a combination of >or=5 swollen joints, >or=5 painful joints
      and erythrocyte sedimentation rate >or=10 mm/h.) METHODS: Patients with active
      rheumatoid arthritis taking MTX >or=12.5 mg/week for >or=3 months were included
      in this 16 week, randomised, open-label study. Patients were randomly assigned to
      either ETN (25 mg subcutaneous injection twice weekly) added to the baseline dose
      of MTX or ETN monotherapy. RESULTS: 315 patients were randomised to ETN (n = 160)
      or ETN plus MTX (n = 155). The primary end point, DAS28 (4) improvement of >1.2
      units, was achieved by 72.8% and 75.2% of patients treated with ETN and those
      treated with ETN plus MTX, respectively, with no significant difference (p =
      0.658) between the two groups. The European League Against Rheumatism response
      criteria of good or moderate response was attained by 80.0% of patients in the
      ETN group and by 82.4% of patients in the ETN plus MTX group. American College of
      Rheumatology 20%, 50% and 70% response rates achieved by both groups were also
      similar: 71.0% v 67.1%, 41.9% v 40.1% and 17.4% v 18.4%, respectively. The rates
      of adverse and serious adverse events were similar between the treatment groups.
      CONCLUSION: Both the addition of ETN to MTX and the substitution of ETN for MTX
      in patients with rheumatoid arthritis who had an inadequate response to MTX
      resulted in substantial improvements in clinical signs and symptoms and were
      generally well-tolerated treatment strategies for improving clinical signs and
      symptoms of rheumatoid arthritis.

PMID- 16464989
TI  - A discussion of silver as an antimicrobial agent: alleviating the confusion.
AB  - Within the last 3 to 5 years, many silver-based antimicrobial dressings have
      become available and more are on the way. However, sometimes dressing
      manufacturers and authors make claims and send messages that conflict with data
      and conclusions in the literature, creating confusion for clinicians. A
      literature review of six relevant and frequently discussed topics was conducted.
      Pre-clinical and clinical study data suggest that: a) bacterial resistance to
      silver may occur, b) silver dissociation is affected by the test medium used, c)
      bactericidal activity differences may be a function of the bacterial strain used
      for testing, d) higher rather than lower levels of silver may be needed because
      Ag+ binds to proteins and nucleic acids, e) rapid delivery of silver (ie, rate of
      kill) may be a positive factor when considering prevention of silver resistance
      and biofilm formation, and f) based on the vast majority of in vivo studies
      available, silver does not adversely effect viable cells; thus, is not
      cytototoxic. Continued research into the implications of the data is warranted.

PMID- 16464990
TI  - Silver deposition and tissue staining associated with wound dressings containing
      silver.
AB  - Argyria is the general term used to denote a clinical condition in which
      excessive administration and deposition of silver causes a permanent irreversible
      gray-blue discoloration of the skin or mucous membranes. The amount of
      discoloration usually depends on the route of silver delivery (ie, oral or
      topical administration) along with the body's ability to absorb and excrete the
      administered silver compound. Argyria is accepted as a rare dermatosis but once
      silver particles are deposited, they remain immobile and may accumulate during
      the aging process. Topical application of silver salts (eg, silver nitrate
      solution) may lead to transient skin staining. To investigate their potential to
      cause skin staining, two silver-containing dressings (Hydrofiber and
      nanocrystalline) were applied to human skin samples taken from electively
      amputated lower limbs. The potential for skin discoloration was assayed using
      atomic absorption spectroscopy. When the dressings were hydrated with water, a
      significantly higher amount of silver was released from the nanocrystalline
      dressing compared to the Hydrofiber dressing (P <0.005), which resulted in
      approximately 30 times more silver deposition. In contrast, when saline was used
      as the hydration medium, the release rates were low for both dressings and not
      significantly different (silver deposition was minimal). Controlling the amount
      of silver released from silver-containing dressings should help reduce excessive
      deposition of silver into wound tissue and minimize skin staining.

PMID- 16464991
TI  - Negative pressure wound therapy to treat peri-prosthetic methicillin-resistant
      Staphylococcus aureus infection after incisional herniorrhaphy. A case study and
      literature review.
AB  - The preferred treatment for incisional hernias occurring post laparotomy involves
      use of prosthetic mesh. If this mesh becomes infected, it may have to be removed
      to achieve wound healing. A patient with a methicillin-resistant Staphylococcus
      aureus-infected prosthetic mesh received negative pressure wound therapy to help
      facilitate healing without removing the prosthetic mesh applied to manage his
      hernia. After almost 4 weeks of treatment, the wound was closed secondarily. The
      literature contains many case studies about the use of NPWT for a variety of
      wounds but information about its safety and effectiveness for managing
      methicillin-resistant Staphylococcus aureus-infected prosthetic mesh is limited.
      The results of this case study add to the evidence that controlled clinical
      studies are warranted.

PMID- 16464992
TI  - Pressure ulcers in German nursing homes and acute care hospitals: prevalence,
      frequency, and ulcer characteristics.
AB  - In German healthcare facilities, research-based knowledge of pressure ulcers and
      their relation to patient characteristics is limited. To provide information for
      national and international comparison on pressure ulcers and related issues, two
      cross-sectional surveys were conducted among 21,574 German hospital patients and
      nursing home residents (147 institutions total) in 2002 and 2003. Prevalence and
      frequency rates of pressure ulcers in people at risk (Braden score of </=20) in
      different institution types were compared and descriptive data on severity,
      location, history, and origin of 3,857 wounds were analyzed to examine the
      relationship between age, body mass index, and Braden score and the frequency and
      severity of wounds. The studies found that among all persons at risk, pressure
      ulcer prevalence was 21.1% and that the number of pressure ulcers per person was
      higher in hospitals (1.91, 24.6%) than in nursing homes (1.42, 13.9%). In
      addition, in hospital patients and nursing home residents, 36.4% and 46.7% of
      wounds, respectively, were grade 2 severity and higher. In both types of
      institutions, the most common pressure ulcer locations were the lower back and
      the heels. In hospital patients, 51.4% of pressure ulcers were facility-acquired,
      compared to 60.2% in nursing homes. In hospital patients and nursing home
      residents, 7.4% and 29.7% of wounds, respectively, had existed for more than 3
      months. The studies also found that persons with lower Braden scale scores had
      more ulcers and more severe pressure ulcers. Analysis of wounds in this large
      patient population provides more detailed information about the problem of
      pressure ulcers and should help improve prevention and treatment.

PMID- 16464993
TI  - Developing a pressure ulcer risk assessment scale for patients in long-term care.
AB  - Previous pressure ulcer risk assessment scales appear to have relied on opinions
      about risk factors and are based on care setting rather than research evidence.
      Utilizing 21 existing risk assessment scales and relevant risk factor literature,
      an instrument was developed by Finnish researchers that takes into account
      individual patient risk factors, devices and methods applied in nursing care, and
      organizational characteristics. The instrument underwent two pilot tests to
      assess the relevance and clarity of the instrument: the first involved 43 nurses
      and six patients; the second involved 50 nurses with expertise in wound care.
      Changes to questionnaire items deemed necessary as a result of descriptive
      analysis and agreement percentages were completed. After pilot testing, the final
      instrument addressed the following issues: 1) patient risks: activity, mobility
      in bed, mental status, nutrition, urinary incontinence, fecal incontinence,
      sensory perception, and skin condition; 2) devices and methods used in patient
      care: technical devices, bed type, mattress, overlay, seat cushions, and care
      methods; and 3) staff number and structure, maximum number of beds, and beds in
      use (the last group of questions were included to ensure participants understood
      the items; results were not analyzed). The phases of the study provided an
      expeditious means of data collection and a suitable opportunity to assess how the
      instrument would function in practice. Instrument reliability and validity were
      improved as a result of the pilot testing and can be enhanced further with
      continued use and assessment.

PMID- 16464994
TI  - Implementing a pressure ulcer prevention program and enhancing the role of the
      CWOCN: impact on outcomes.
AB  - Hospitals in the US are increasingly concerned with the rising number of hospital
      acquired pressure ulcers. To reduce its 2002-2003 average hospital-acquired
      pressure ulcer prevalence rate of 9.2%, a regional medical center in southeastern
      US initiated a process improvement and education program. Quarterly pressure
      ulcer prevalence studies were conducted and the Medical Intensive Care Unit was
      found to have the highest number of hospital-acquired pressure ulcers among the
      five units participating in the study. As part of a new Pressure Ulcer Strategic
      Plan, significant changes were made to the organizational infrastructure and
      processes, which included implementing the Braden Risk Scale Assessment Tool in
      place of the Norton Risk Scale, developing a pressure ulcer prevention protocol,
      creating Pressure Ulcer/Skin Tear Physician orders for nurses, establishing a
      Skin Resource Team, and providing additional education, training, and other
      relevant resources. Better appreciation for and enhanced utilization of Certified
      Wound Ostomy Continence Nurses were encouraged. New support surfaces were
      purchased. Implementing these changes resulted in a decrease in the quarterly
      hospital-acquired pressure ulcer prevalence in participating units, including the
      Medical Intensive Care Unit where rates dropped from a high of 29% to near 0%.
      Clinicians now approach pressure ulcers as preventable rather than inevitable and
      view Certified Wound Ostomy Continence Nurses as resources and clinical experts
      for prevention and treatment. Overall quality of care and financial resource
      utilization also have substantially improved.

PMID- 16464995
TI  - [The editorial board's agenda].

PMID- 16464996
TI  - [The risk of influenza pandemic and the preparedness against it].

PMID- 16464997
TI  - [Eating disorders: symptomatology, course and prognosis, epidemiology, and
      psychiatric comorbidity. Review article].
AB  - OBJECTIVE: Eating disorders are a group of serious psychiatric disorders that
      affect primarily young women and can have serious consequences on their lives and
      their families. Eating disorders are characterized by disordered eating behaviour
      with desire for thinness that can result in serious physical and psychological
      symptoms and death. Eating disorders tend to run a chronic course. Psychiatric
      comorbidity and physical complications are common among eating disordered
      patients and these issues need to be taken into consideration during treatment.
      Prevalence and incidence of eating disorders appears to be increasing in Western
      societies and follow increased prosperity and obesity problems. There is no
      reason to believe that the situation is different in Iceland but research is
      lacking. In this review article we address the main symptoms and diagnostic
      criteria of three types of eating disorders, that is anorexia nervosa, bulimia
      nervosa and eating disorder not otherwise specified. The course and prognosis,
      epidemiology, and psychiatric comorbidity of eating disorders will also be
      presented. Finally, we discuss the services available to eating disordered
      patients here in Iceland and the need for further development of the services.

PMID- 16464998
TI  - [The use weight loss menues for overweight Icelanders aged 20-40 years].
AB  - OBJECTIVE: To carry out an intervention study on weight loss menues for young
      overweight Icelanders giving 30% less energy than calculated energy need for
      unchanged body weight, with the percentage of energy giving nutrients in
      congruity with official recommendations. MATERIAL AND METHODS: Subjects were
      women (n=71) and men (n=43) aged 20-40 y, having a body mass index (BMI) in the
      range 28-32 kg/m2. The daily energy for weight balance at baseline was estimated
      for each individual and a menu prepared to give 30% less energy. Energy
      distribution was 50% from carbohydrates, 20% from proteins and 30% from fat.
      Nutritionists gave advice and taught the participants how to use the menus.
      Weight and height were measured at baseline and at the end of the eight weeks
      intervention. RESULTS: According to a 30% energy reduction from the daily energy
      need the menus were prepared to give on average (-/+SD) 1693-/+108 kcal and 1349
      /+53 kcal for men and women, respectively. The average weight loss was five kg
      during the eight weeks intervention, 625 g per week (<0.001). Men lost more
      weight (around 740 g/week) than women (525 g/week, P=0.003). The proportion of
      obese (BMI> or =30 kg/m2) decreased from being 47% to 15% during the
      intervention. CONCLUSION: Menus with the proportion of energy giving nutrients in
      line with official recommendations, together with nutritional counseling, prove
      to be a successful mean to bring off weight loss among young overweight Icelandic
      individuals. The method can be useful in clinical settings in the battle against
      increasing prevalence of overweight and obesity. It is likely that thorough
      follow-up treatment is necessary to maintain the weight loss.

PMID- 16464999
TI  - [The new international guidelines for cardiopulmonary resuscitation and emergency
      cardiovascular care].
AB  - Recently the American Heart Association and the European Resuscitation Council
      published new guidelines for cardiopulmonary resuscitation and emergency
      cardiovascular care. These new guidelines are the result of extensive review of
      the scientific literature in this field by The International Liason Committee on
      Resuscitation. There are some important changes in the new guidelines with a
      major emphasis on the importance of basic life support, especially chest
      compressions. The guidelines also promote early defibrillation while the role of
      pharmacologic therapy during cardiopulmonary resuscitation is not as clear. This
      article discusses the highlights of the new guidelines.

PMID- 16465000
TI  - Steroid resistant nephrotic syndrome recent developments.

PMID- 16465001
TI  - Cyclosporine in steroid dependent and resistant childhood nephrotic syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of cyclosporine (CyA) monotherapy in steroid
      resistant (SRNS) and steroid dependent (SDNS) nephrotic syndrome in children.
      DESIGN: A retrospective study. SETTING: Tertiary kidney care center for children
      at Bangalore. METHODS: Forty-one children with SDNS and SRNS with normal renal
      functions were treated with CyA at a dose of 6 mg/kg/day initially and maintained
      at 3 to 4 mg/kg/day if remission was sustained. The dosage was adjusted according
      to the CyA blood levels in non-responders. RESULTS: The median age of patients
      was 93 months (range 48-936) months. Thirteen children had minimal change disease
      (MCNS), 10 had mesangial proliferative glomerulonephritis (GN). Ten had membrano
      proliferative (GN) (MPGN) and 8 had focal segmental glomerulosclerosis (FSGS).
      Median age at onset of disease and median time for CyA usage from disease onset
      was 22 months and 16 months respectively. Median duration of CyA therapy was 24
      months (range 6-72) months. The data was analyzed to determine significance of
      variables on the outcome. Median follow up was 71 months (range 20-205) months.
      Eleven children were CyA resistant. Of the remaining 30 who were CyA responders,
      22 (73.33%) were CyA dependent. Seven children developed chronic renal failure
      (CRF). CONCLUSIONS: The predictors for CyA non-responsiveness were steroid
      resistance, non MCNS on biopsy and longer duration between onset of nephrotic
      syndrome and CyA usage, irrespective of the age of onset of the disease. There
      was a higher incidence of CyA dependence among young responders. Patients with
      CyA resistance are at high risk for significant infections and CRF.

PMID- 16465002
TI  - Dose end-tidal carbon dioxide measurement correlate with arterial carbon dioxide
      in extremely low birth weight infants in the first week of life?
AB  - OBJECTIVE: To study the correlation and agreement between end-tidal carbon
      dioxide (EtCO2) and arterial carbon dioxide (PaCO(2)) in ventilated extremely low
      birth weight (ELBW) infants in the first week of life. METHODS: Retrospective
      chart review of all ELBW (<1,000 g) infants admitted to a level III NICU from
      January 2003 to December 2003. Data collected included demographic details and
      simultaneous EtCO(2) (mainstream capnography) and arterial blood gas values (pH,
      PaCO(2), PaO(2)). OUTCOME: The correlation coefficient, degree of bias with 95%
      confidence interval between the EtCO(2) and PaCO(2). RESULTS: There were 754 end
      tidal and arterial CO(2) pairs from 31 ELBW infants (21 male and 10 female). The
      overall EtCO(2) values were significantly lower than PaCO(2) value. In only
      89/754(11.8%) pairs, the EtCO(2) was higher than the PaCO(2). The overall bias
      was 5.6 +/- 6.9 mmHg (95% C.I. 5.11-6.09). The intraclass correlation coefficient
      was 0.81. Using EtCO2 ranges of 30 to 50 mmHg, the capnographic method was able
      to identify 84% of instances where PaCO(2) was between 35 (<35 = hypocarbia) and
      55 mmHg (>55= hypercapnia). CONCLUSIONS: There is good correlation and agreement
      between end-tidal CO(2) and arterial CO(2) in ELBW infants in the EtCO(2) range
      30-50 mmHg. End-tidal CO(2) monitoring can be helpful in trending or for
      screening abnormal PaCO(2) values in ELBW infants in first week of life.

PMID- 16465003
TI  - National pharmacovigilance program.

PMID- 16465004
TI  - Patterns and problems of sleep in school going children.
AB  - This study was conducted to assess the sleep habits and problems of 103 young
      school going healthy children (3-10 yr) during their visit to hospital for minor
      illnesses or routine health visits for immunization. The average duration of
      daily sleep (nocturnal and daytime nap) was 10.32 and the percentage of children
      who took regular daytime nap was 28.2%. Co- sleeping, a traditional cultural
      practice in India was found in 93% of the children. Sleep related problems were
      reported in 42.7% children that included nocturnal enuresis (18.4%), sleep
      talking (14.6%), bruxism (11.6%) nightmares (6.8%), night terrors (2.9%) snoring
      (5.8%) and sleepwalking (1.9%). On univariate analysis, sleep related problems
      were notably common if it was nuclear family (Fishers exact test; P = 0.01),
      mother was younger in age (Mann Whitney U test; P= .04) and less educated (Mann
      Whitney U test; P=.04). However, when these predictors were entered
      simultaneously into a logistic regression model, only nuclear family remained as
      significant predictor of sleep related disorders (odds ratio 2.41; CI; 1.04
      5.57). We conclude that sleep problems are frequent among healthy school going
      children seen at general pediatric practice.

PMID- 16465005
TI  - Steroid resistant nephrotic syndrome is sustained remission attainable.
AB  - A prospective study was undertaken to find out the benefit of immunosuppressive
      therapy(IV methyl prednisolone followed by oral prednisolone therapy for one year
      along with six doses of pulse monthly IV cyclophosphamide) in children with
      steroid resistant nephrotic syndrome. Thirty-four children with steroid resistant
      nephrotic syndrome were treated with above regime. The remission of the disease
      was determined at the end of first, second and third year. The above protocol
      could induce and maintain remission in 81.8% of children with minimal change
      nephrotic syndrome, 66.7% of children with diffuse mesangial proliferation and in
      only 16.7% of children with focal segmental glomerulosclerosis at the end of
      three years of the study. The therapy of IV methyl prednisolone followed by oral
      prednisolone for one year with 6 monthly pulse IV cyclophosphamide, is beneficial
      in children with steroid resistant minimal change disease and diffuse mesangial
      proliferative glomerulonephritis. The therapy is not effective in focal segmental
      glomerulosclerosis.

PMID- 16465006
TI  - Pediatric renal transplantation: the Bangalore experience.
AB  - A retrospective analysis was done on 47 pediatric renal transplants performed
      over last 16 years at Bangalore, Karnataka. The median age and weight of the
      recipients at transplantation were 120 months and 21 kg respectively; male to
      female ratio was 30 to 17. Twenty two children had underlying glomerular disease
      and 23 had tubulointerstitial disease. Preemptive transplantation was done in
      33.3% of patients, 57.2% received hemodialysis and 9.5% received peritoneal
      dialysis prior to transplantation. The mean duration of dialysis was 2.6 months.
      The most common source of donor organ was the mother. Immunosuppression
      medications included cyclosporine, azathioprine, and corticosteroids. Graft
      survival at 1 year, 5 years, and 10 years was 80%, 45.8% and 37.5% respectively.
      Renal transplantation is the most optimal way to manage children with ESRD with
      satisfactory long term results.

PMID- 16465007
TI  - Accuracy of parental and child's reports of changes in symptoms of childhood
      asthma.
AB  - This cohort study was conducted to evaluate the accuracy of parental and child's
      reports of changes in asthma symptoms. Fifty three asthmatic children and their
      parents were interviewed at enrollment and after 4 and 8 weeks. The outcomes were
      parental and child's reports of changes in asthma symptoms, changes in mean daily
      symptom scores and changes in pulmonary function. Among patients 6 to 10 years
      old, parental reports were more strongly than child's reports to correlate with
      changes in mean daily symptom scores (r: 0.54 vs 0.23). In patients aged 11 yr or
      older, parental and child's reports were equally correlated with changes in mean
      daily symptom scores (r: 0.63 vs 0.57). In both age groups, neither parental nor
      child's reports were significantly correlated with changes in pulmonary function.
      Conclusion Parental reports of changes in asthma symptoms are more reliable than
      child's reports in patients under 11 yr. Among patients aged 11 yr or older,
      child's reports are so valid as their parents reports for clinical judgment of
      asthma control.

PMID- 16465008
TI  - Steroid resistant nephrotic syndrome: role of histopathology.
AB  - This study was conducted to (1) see the histopathological distribution of
      different subtypes in steroid resistant nephrotic syndrome (SRNS) and (2) compare
      the clinical, biochemical parameters and outcome between Minimal Change Disease
      (MCD) with non-MCD subtypes in response to immunosuppressive therapy. A
      retrospective analysis was done of data on all biopsy proven children with
      idiopathic SRNS (no response to 4 weeks of standard prednisone therapy (60
      mg/m(2)/day)) referred to our institute over last 12 years. They were treated
      with one of the following medications: oral or intravenous cyclophosphamide,
      cyclosporine or combination of dexamethasone and azathioprine. A comparison was
      done of the demographic clinical and biochemical features different
      histopathologies. We studied 136 children with SRNS (100 M, 36 F). They accounted
      for 15.1%(136/900) of all children with idiopathic nephrotic syndrome. Focal
      segmental glomerulosclerosis (FSGS) was the commonest 80/136 (59%), followed by
      MCD (17.6%). Children with non-MCD had a significantly greater prevalence of
      microhematuria as compared to MCD. The other baseline clinical and biochemical
      features including the glomerular filtration rate (GFR) were similar. After a
      mean follow up of 46 (8-148) months, a significantly greater children with non
      MCD 65/112) continued to be proteinuric as compared to the MCD (3/24) (p=0.0001).
      FSGS was the commonest cause of SRNS in our patient population. Children with
      SRNS secondary to MCD are more likely to achieve remission as compared to non-MCD
      subtypes and have a better long-term prognosis. Hence kidney biopsy is of
      significant prognostic value in SRNS.

PMID- 16465009
TI  - Carmi syndrome complicated by pharyngo-esophageal perforation.
AB  - We describe a neonate having congenital pyloric atresia (CPA) associated with
      epidermolysis bullosa (EB), also known as Carmi syndrome. The case is unusual as
      it was complicated with pharyngo-esophageal perforation (PEP) and a definite
      family history of EB in pervious generations could be recorded.

PMID- 16465010
TI  - Neonatal jaundice and splenic hematoma.
AB  - In the newborn period, unconjugated hyperbilirubinemia (UHB) is common,
      multifactoral, and associated with a variety of physiologic and pathologic
      conditions. The most commonly identified pathologic cause leading to
      hyperbilirubinemia is hemolytic disease of the newborn. We report a five-days-old
      female infant with neonatal jaundice secondary to splenic hematoma.

PMID- 16465011
TI  - Fluoxetine withdrawal syndrome in the newborn.
AB  - A term baby was admitted to our neonatal unit with jitteriness, hypertonia,
      sneezing and fever. Her mother was on 20 mg of fluoxetine throughout her
      pregnancy. These symptoms which were possibly due to fluoxetine withdrawal lasted
      only for a short while. We attempt to look at the reported prevalence of this
      condition in the literature.

PMID- 16465012
TI  - Fixed cutaneus sporotrichosis.

PMID- 16465013
TI  - Bleomycin induced flagellate pigmentation.

PMID- 16465014
TI  - Familial radial dyplasia with renal ectopia.

PMID- 16465015
TI  - Plasmapheresis in acute disseminated encephalomyelitis.

PMID- 16465016
TI  - Lipoblastoma in infancy.

PMID- 16465017
TI  - Wheat grass juice in thalassemia.

PMID- 16465019
TI  - Hepatic abscess caused by Salmonella typhi.

PMID- 16465020
TI  - Allogeneic peripheral blood stem cell transplantation in aplastic anemia.

PMID- 16465021
TI  - Dyslexia: association with attention deficit hyperactivity disorder.

PMID- 16465023
TI  - What should be done when authors do not respond.

PMID- 16465024
TI  - [Bone destruction caused by osteoclasts].
AB  - Lipopolysaccharide (LPS) and muramyl dipeptide (MDP) are components of bacterial
      cell walls that cause innate immune responses and inflammation. Toll-like
      receptor 4 (TLR4) is a receptor for LPS and transduces signals through myeloid
      differentiation factor 88 (MyD88), which plays essential roles in the
      TLR/interleukin (IL)-1R signaling and activates MAP/ERK kinase (MEK)/ERK pathway
      to induce receptor activator of NF-kappaB ligand (RANKL) expression in
      osteoblasts. Osteoblasts express nucleotide oligomerization domain (NOD)2, an
      intracellular sensor for MDP, in response to LPS, IL-1 and TNF. NOD2 binds
      receptor-interacting protein (RIP2), a serine/threonine kinase which transduces
      NF-kappaB signaling. MDP synergistically enhances osteoclast formation induced by
      LPS, IL-1 and TNF through RANK ligand up-regulation in osteoblasts. TLR4 and NOD2
      recognize bacterial components on cell surfaces and inside cells, respectively,
      and these signals up-regulate RANKL expression in osteoblasts, which results in
      enhancing osteoclast formation and function.

PMID- 16465025
TI  - [The mechanism of bone resorption in chronic inflammation of periodontal
      disease].
AB  - Periodontal disease is caused by infections with oral periodontitis-associated
      microorganisms. Virulence factors like lipopolysaccharide (LPS) from those
      microorganisms initiate host immune response and gingival chronic inflammation.
      As a result, elevated receptor activator of NF-kappaB ligand (RANKL) expression
      stimulates alveolar bone resorption followed by loss of teeth.

PMID- 16465026
TI  - [Alveolar bone resorption in animal models of periodontitis].
AB  - Periodontitis is a chronic inflammatory disease caused by infection of
      periodontopathic bacteriae, which induces alveolar bone resorption, tooth
      mobility, and finally tooth loss. In order to clarify the pathogenesis and to
      develop prevention and treatment of periodontitis, it is important to establish
      animal models of periodontitis. In this article, we showed several types of
      experimental models previously reported, and also showed a rat model using
      ligature and a hamster model using periodontopathic bacteria, both we used in our
      laboratory. Micro computed tomography (CT) analysis and histological observation
      revealed the inflammatory localization and osteoclast appearance in periodontal
      tissues. The usefulness of animal models of periodontitis is demonstrated by
      exhibiting an inhibitory effect of bisphosphonate and prostaglandin E(2) on
      alveolar bone resorption in our experimental systems.

PMID- 16465027
TI  - [Periodontal examination for alveolar bone resorption].
AB  - Periodontitis is an inflammatory disease which is involved with gingival
      attachment loss and an alveolar bone resorption. Traditional methods for taking X
      ray photograph or assessments of probing depth and clinical attachment level are
      provided the previous periodontal tissue breakdown, however, these methods are
      hard to confirm the disease activity and predict of the disease outcome.
      Therefore, the component or quality of gingival crevicular fluid (GCF), which is
      directly, reflects the gingival inflammation is noticed. It firstly describes
      that GCF containing the inflammatory mediator, cytokine, and bone markers are not
      only related to the bone resorption but also affected the periodontal disease
      activity. As the final part in the series it lastly discusses the possible uses
      of predictive diagnostic tests of periodontal disease activity in dental
      practice.

PMID- 16465028
TI  - [Muscular power of masticating muscles and mandibular osteoporosis].
AB  - Whereas the most powerful stimuli for bone formation is supposed to be a
      stretching of muscles, Frost HM classified the effect of muscle on bone mineral
      density (BMD) into various types: 1. age-related loss of bone mineral density
      (BMD) is partly due to loss of muscular wasting, 2. the increase of BMD in
      obesity is due to the increase in muscular power to support the increased body
      weight and 3. the decrease of BMD in chronic wasting disease is partly due to the
      decrease in muscular power. Likewise, the decrease in BMD in mandibular alveolar
      bones will be partly due to the decrease in the power of masticating muscles, if
      such exists. A case report of mitochondrial encephalo-myopathy associated with
      impaired function of cranial nerves involving trigeminus nerves and impaired
      function of masticating muscles and dysphagia. This patient showed decrease in
      alveolar BMD and atrophy of mandibular.

PMID- 16465029
TI  - [Osteoporosis and periodontal disease in postmenopausal women: association and
      mechanisms].
AB  - Many studies have attempted to define the relationship between postmenopausal
      osteoporosis and periodontal disease. Most studies support a positive association
      between these common diseases; however, many are cross-sectional in nature,
      include relatively small sample sizes, and have inadequate control of potential
      confounding factors, such as age, gender, hormone intake, race, and smoking,
      limiting our understanding of the nature of the relationship between these
      diseases. Clinical conditions causing low estrogen environments in postmenopausal
      women allow T- and B-cell abnormalities, increased local production of the bone
      active cytokines (i.e., Interleukin-1, -6 and -8, tumor necrosis factor [TNF]
      alpha) and a rise in prostaglandin E(2), resulting in the progression of
      periodontitis.

PMID- 16465030
TI  - [The relationship between periodontal disease and osteoporosis in animals].
AB  - Osteoporosis is suspected as a potential risk factor in periodontal disease.
      However, the detailed relationship between these diseases is unclear. The
      particular models of laboratory animals for the both diseases are needed to
      clarify the interactive influence route. In this article, we introduce the animal
      models for both diseases, review the relationship between osteoporosis and
      periodontal disease in animals and report our laboratory study. The purpose of
      our study was to investigate the effect of an ovariectomy on the progression of
      experimental periodontitis in rats. Thirty female Sprague-Dawley rats as control,
      30 sham-operated rats and 30 ovariectomized rats (OVX group) were included. In
      the maxillary molars of every rat, a nylon thread was ligated to induce
      experimental periodontitis. The results were as follows : at 6 and 12 weeks in
      the OVX group, the levels of bone mineral density (BMD) had decreased more
      significantly. The periodontal tissues in the OVX group showed a severer
      inflammation and alveolar bone resorption. From these results, it is suggested
      that the osteoporotic conditions may affect the progression of periodontal
      lesions in rats. It will be necessary to clarify with a molecular mechanism with
      the establishment of animal models in both diseases in the future.

PMID- 16465031
TI  - Osteoporosis and the risk of tooth loss.
AB  - Osteoporosis and osteopenia may influence periodontal disease and tooth loss.
      Although many studies suggest that in elderly men and women, maintenance of
      normal bone mineral density is associated with improved tooth retention, the
      evidence is still inconclusive. Hormone replacement therapy and calcium and
      vitamin D supplements that are used to prevent or treat osteoporosis appear to
      have beneficial effects on tooth retention as well. Future prospective studies,
      including randomized clinical trials, are needed to confirm these findings.

PMID- 16465032
TI  - [Screening for osteoporosis by dental panoramic radiographs].
AB  - Cortical measurements (width and shape) of the mandible detected on panoramic
      radiographs are associated with bone mineral density of the spine and the femur,
      risk of osteoporotic fractures and bone turnover. Diagnostic efficacy of cortical
      measurements for identifying postmenopausal women with osteoporosis is almost
      similar to that of questionnaire-based screening tool. Dental clinic may be one
      of valuable strongholds in screening for osteoporosis.

PMID- 16465033
TI  - [Increased bone resorption by sympathetic nervous activity].
AB  - Recent experimental studies showed the dynamic neural regulation of local bone
      metabolism. Increased sympathetic nervous activity has been demonstrated to cause
      bone loss via an increase in bone resorption and a decrease in bone formation.
      This review summarized both in vivo and in vitro evidences implicating
      sympathetic neuron action in bone resorption.

PMID- 16465034
TI  - [Searches for the genes associated with periodontitis with gene polymorphisms].
AB  - Periodontitis is considered to be a common disease which onset and progression
      seems to be associated with genetic factors and many environmental factors,
      especially, the amount and composition of bacterial plaque. Previous studies have
      shown an association between periodontitis and polymorphisms in some genes,
      however, the critical loci for periodontal disease have not yet been identified.
      In the future, whole-genome association studies with periodontitis would suggest
      that the genetic susceptibility loci for periodontitis and provides important
      information for elucidation of the molecular mechanisms involved in the etiology
      of periodontal disease.

PMID- 16465035
TI  - [The pathophysiology of osteoporosis/osteopenia in gene mutant mice].
AB  - Osteoporosis is a systemic skeletal disease characterized by low bone mass and
      the microarchitectural deterioration of bone tissue. The pathophysiology of
      osteoporosis is complex, involving a broad spectrum of endogenous and
      environmental factors. Recently, molecular and genetic approaches are revealing
      that genetic backgrounds are important for the pathophysiology of osteoporosis.
      We discuss about recent findings of osteoporosis and osteopenia caused by
      monogenic mutations in humans and mice.

PMID- 16465036
TI  - [Chemotherapy as a periodontal treatment].
AB  - As the number of aged periodontal patients with systemic disease has increased,
      it is important to consider the risk of periodontal surgery. Combination of non
      surgical periodontal and local/systemic chemotherapy has reported to improve
      outcome of patients significantly. Local/systemic chemotherapy is also effective
      for periodontal disease on dental implant. We discuss these new treatment for
      periodontal disease.

PMID- 16465037
TI  - [Possibility of clinical usage of BMP in periodontal application; basic study].
AB  - It is necessary for using some carriers which hold bone morphogenetic protein
      (BMP) activity and maintain its osteoinductive ability, when BMP is applied to
      the tissue regeneration of the bone defect caused by periodontal diseases. It is
      indispensable for using some carriers which hold BMP activity and maintain its
      osteoinductive ability, when BMP is applied to the tissue regeneration of the
      bone defect caused by the diseases. Metals, ceramics and polymers are used for
      such carriers, and especially, polymers are indispensable. It is also important
      to prevent the penetration of epithelial tissue downgrowth, therefore, we
      innovated a noble resin material which can be formed to the thin film and has a
      property of light curing. Composite of this resin and BMP stably induced new
      bone. Cartilage induction in the organ culture on the artificial membrane was
      also succeed, and it will extend to the bone regeneration by means of re
      transplantation of patient's derived tissues after the incubation.

PMID- 16465038
TI  - [Pre-clinical and clinical studies on bone morphogenetic proteins for
      regenerative therapies in dentistry field].
AB  - Many researches were done on the application of bone morphogenetic proteins
      (BMPs) for periodontal regeneration, and bone regeneration followed by the
      insertion of dental implants. There are many reports which suggested that BMPs
      enhanced alveolar bone and cementum formations in the pre-clinical studies on
      periodontal regeneration. However, it is suggested that ankylosis might disturb
      the ideal periodontal regeneration. There are also many reports which suggested
      that BMPs were effective for alveolar ridge augmentation for the insertion of
      dental implant in pre-clinical and clinical studies. There are great hopes that
      the application of BMPs for the regenerative therapies on diseases involving bone
      loss.

PMID- 16465039
TI  - [Application of bisphosphonates for periodontitis].
AB  - Bisphosphonates are known as highly effective inhibitors of osteoclastic bone
      resorption that selectively affect osteoclasts. They are world-wildly used for
      the treatment of metabolic bone diseases with excessive bone resorption such as
      osteoporosis and Paget's disease. Alveolar bone loss in periodontitis results
      from local inflammatory reactions by periodontopathic bacteria. It has been
      reported that bisphosphonates efficiently prevent experimentally induced alveolar
      bone resorption in animals with periodontitis, and that bisphosphonate therapy
      improves the outcome of periodontal treatment in human being. Administration of
      bisphosphonates may be an appropriate adjunctive treatment to preserve
      periodontal bone mass. Further studies are needed regarding topical drug delivery
      system, effective dose and frequency of administration, possible side effects,
      and which bisphosphonate is suitable for periodontitis.

PMID- 16465040
TI  - [Dental implant treatment to osteoporosis patients].
AB  - Prosthetic treatment with dental implant is currently reliable. Since dental
      implant treatment can yield much satisfaction to patients compared to other
      treatments, such as bridge or removable denture, number of patients, who desire
      to be treated with dental implant, is increasing. Cortical bone of female
      mandible is thin compared to that of male mandible and postmenopausal condition
      decreases bone density of the cancerous bone. Furthermore, estrogen-deficiency
      delays implant and bone connection. Thus, it is necessary to treat osteoporotic
      patients with dental implants carefully compared to usual patients.

PMID- 16465041
TI  - [Application of dietary supplement to periodontal disease and osteoporosis].
AB  - It is known that there is a relationship between various systemic diseases, life
      style and periodontal disease. In such a situation, it is becoming clear a
      relationship between the systemic bone density and the mandibular bone, alveolar
      bone density and clinical periodontal parameters. And it is also cleared that to
      lower common risk factors related to these conditions might be useful to prevent
      osteoporosis and periodontal disease. As it is reported that medical treatment
      such as hormone replacement therapy (HRT) is effective not only preventing
      lowering skeletal bone density but also maintaining mandibular and alveolar
      bones, it is also considered that continuing supplementation of some nutritions
      such as calcium and isoflavone is also expected to have preventive effects.

PMID- 16465042
TI  - [Genome-wide analysis for transcriptional regulation of chondrogenesis-related
      genes].
AB  - Transcriptional factor Sox9 plays a central role in development of chondrogenesis
      with stage specificity and in tissue specificity. Sox9 with a number of
      transcriptional cofactors is a critical regulator in genes such as COL2,
      chondorocyte specific gene. We report here our new large scale approaches : 1)
      Whole mount in situ hybridization (WISH), 2) High through-put human cDNA
      transfection assay. These genome-wide approaches have a possibility of discovery
      for new transcription factors in chondrogenesis.

PMID- 16465043
TI  - [Sox family regulate chondrogenesis].
AB  - Recent studies reveal that Sox family play crucial roles in cell lineage
      determination and cell differentiation during embryogenesis. In vitro analyses of
      type II collagen gene strongly suggested that Sox5, 6, and 9 are involved in
      cartilage-specific expression of type II collagen gene. Indeed, mouse genetics
      approaches clearly indicate that these Sox family transcription factors are
      essential for chondrogenesis.

PMID- 16465044
TI  - Effect of inhaled steroids on increased collagen synthesis in asthma.
AB  - BACKGROUND: We previously reported that sputum levels of procollagen type I C
      terminal peptide (PICP), a marker of ongoing collagen type I deposition, are
      increased in proportion to airway inflammation in asthma patients. OBJECTIVES: In
      this study, we examined the effect of inhaled corticosteroids on increased
      collagen synthesis in step 2-4 asthmatics. METHODS: We compared the sputum PICP
      concentrations of 25 steroid-naive asthmatics, 25 normal volunteers, and 10
      subjects with chronic obstructive pulmonary disease. Asthma subjects were also
      instructed to start fluticasone propionate treatment, and the percentage of
      forced expiratory volume in 1 s, sputum eosinophil counts, sputum PICP
      concentrations, and sputum transforming growth factor-beta-positive cell counts
      before treatment were compared with those 1 month after treatment. RESULTS:
      Sputum PICP concentrations were detected in the following order: asthma group
      >or= chronic obstructive pulmonary disease group > control group. Asthma patients
      showing high sputum PICP belonged to step 4, although there was no correlation
      between sputum PICP and asthma severity. Treatment with fluticasone propionate
      not only significantly improved the mean percentage of forced expiratory volume
      in 1 s (from 66.7 to 87.2%), but also decreased the mean sputum eosinophil counts
      (from 13.4 to 5.8%), the mean sputum PICP concentrations (from 30.8 to 10.2
      ng/ml), and the mean sputum tumor growth factor-beta-positive cells (from 11.3 to
      2.8%). Nevertheless, a significant difference in sputum PICP concentrations was
      still observed between the control group and the steroid-treated asthma group.
      CONCLUSIONS: The present results suggest that inhaled corticosteroid treatment
      might reduce sputum indexes of collagen metabolism and eosinophilic inflammation
      in asthma patients.

PMID- 16465045
TI  - Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet
      cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells.
AB  - BACKGROUND: Interleukin (IL)-13 has recently been reported as the major T-helper
      2 cytokine involved in mucus overproduction and oversecretion in allergic
      airways. However, the relationship between human calcium-activated chloride
      channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully
      investigated. OBJECTIVES: The present study examines whether IL-13 induces the
      expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also
      investigated the relationship between hCLCA1 and MUC5AC expression and the
      development of goblet cell hyperplasia (GCH). METHODS: NHBE cells were isolated
      from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC
      gene and protein expression, as well as GCH were examined in the cells after
      exposure to IL-13. RESULTS: Incubation with IL-13 for 14 and 21 days increased
      the total number of epithelial cells, the number of periodic acid-Schiff (PAS)
      stained epithelial cells, the number of goblet cells, as well as expression of
      mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory
      granules also increased after 21 days of incubation with IL-13. Niflumic acid, a
      chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and
      reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells
      exposed or not to IL-13 expressed IL-13 receptor alpha(1) (IL-13Ralpha(1)), and
      an antibody to IL-13 Ralpha(1) also reduced the number of PAS-positive cells
      after exposure to IL-13. CONCLUSIONS: IL-13 might induce the expression of MUC5AC
      and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might
      also differentiate into goblet cells and become hyperplastic.

PMID- 16465046
TI  - Evaluation of inspiratory muscle function in a healthy austrian population-
      practical aspects.
AB  - BACKGROUND: There is no clear evidence whether inspiratory muscle strength
      (Pi(max)) is closely linked to inspiratory muscle endurance (T(lim)). Moreover,
      normal values of T(lim), measured by flow-resistive loads, have not been
      established. OBJECTIVES: We tried to find answers to the following questions: Is
      it possible to establish normative values of T(lim) when using flow-dependent,
      resistive loads? Are Pi(max) and Borg scale values predictors of T(lim)? Are
      anthropometric and spirometric data closely related to T(lim)? Is it really
      necessary to measure T(lim) in addition to Pi(max) when evaluating inspiratory
      muscle function? METHODS: Sixty-eight healthy Austrian volunteers between 17 and
      75 years of age and with a sedentary lifestyle participated in our study. Pi(max)
      was defined as the maximal inspiratory mouth pressure, measured with a
      differential pressure transducer. T(lim) was determined as the time span until
      exhaustion, while breathing against a resistive loading device. RESULTS: Pi(max)
      values showed a low intra- and high interindividual variability for both sexes
      and were significantly age, weight and height dependent. For male subjects,
      Pi(max) was also significantly related to spirometric parameters. T(lim) values
      showed a very high interindividual variability, but a low intraindividual
      variability. Interestingly, no correlation was found between T(lim) and Pi(max),
      nor lung function parameters and age. CONCLUSIONS: The results indicate that both
      Pi(max) and T(lim) have to be determined when inspiratory muscle function is
      measured. Normal values for T(lim), evaluated by flow-resistive loads, cannot be
      satisfactorily established due to the high interindividual variability.

PMID- 16465047
TI  - N-acetylglucosamine reduces inflammatory response during acute peritonitis in
      uremic rats.
AB  - BACKGROUND: Peritoneal dialysis (PD) induces intraperitoneal inflammation and
      that process may be uremia. The goal of this study is to evaluate the effect of
      uremia on the kinetics of peritonitis and furthermore test the anti-inflammatory
      potential of N-acetylglucosamine (NAG) in a uremic environment. METHODS:
      Experiments were performed on healthy Wistar rats and on animals with impaired
      renal function. Acute PD was performed in all animals with dialysis fluid
      containing either glucose (GLU) or NAG as osmotic solutes. Peritonitis was
      induced by addition of lipopolysaccharide from Escherichia coli (LPS) to the
      dialysis fluid. Transperitoneal transport of water and solutes as well as
      intraperitoneal and systemic inflammation were evaluated. RESULTS: Uremia reduces
      peritoneal permeability to total protein during peritonitis (-33% vs. control, p
      < 0.001) and increases net ultrafiltration (+2.5 +/- 2.2 vs. -2.7 +/- 3.2 ml in
      control, p < 0.001). In uremic rats with peritonitis, reduced dialysate levels of
      the following inflammatory mediators were detected as compared to healthy
      animals: MCP-1 (-15%, p < 0.01); IL-1beta (-53%, p < 0.001), and elastase (-28%,
      p < 0.02). In the serum of uremic rats, the increase in TNFalpha and MCP-1
      concentrations was smaller than in control rats: -44% (p < 0.02) and -39% (p <
      0.001), respectively. NAG used as an osmotic solute in rats with preserved renal
      function decreases intraperitoneal and systemic inflammation during acute
      peritonitis. Drained dialysate volume was increased in the NAG group by 32% (p <
      0.001) and transperitoneal loss of protein was reduced by 21% (p < 0.002). When
      NAG was used as the osmotic solute instead of GLU, intraperitoneal inflammation
      in uremic animals was further reduced: TNFalpha (-40%, p < 0.05); IL-1beta (-49%,
      p < 0.005); MCP-1 (-21%, p < 0.005). The presence of NAG also reduced the
      increased blood level of IL-1beta (-47%,p < 0.02) and MCP-1 (-36%, p < 0.02).
      CONCLUSIONS: Intensity of acute peritonitis is reduced during uremia. NAG exerts
      a systemic and peritoneal anti-inflammatory action under conditions of uremia
      that confirms the potential use of this compound as an osmotic agent in the PD
      fluids that also decreases inflammation.

PMID- 16465048
TI  - Paclitaxel - a tool to prevent stenosis in vascular access for haemodialysis?

PMID- 16465049
TI  - Development of a local perivascular paclitaxel delivery system for hemodialysis
      vascular access dysfunction: polymer preparation and in vitro activity.
AB  - Hemodialysis vascular access dysfunction (HVAD) is currently a huge clinical
      problem. The major cause of HVAD is venous stenosis (as a result of venous
      neointimal hyperplasia) which leads to thrombosis in polytetrafluoroethylene
      dialysis access grafts and fistulae. Despite the magnitude of the clinical
      problem there are currently no effective therapeutic interventions for this
      condition. In an attempt to reduce the morbidity associated with HVAD, we have
      developed and validated a local perivascular paclitaxel release system for use in
      a pig model of arteriovenous graft stenosis. Ethylene vinyl acetate polymers with
      5% paclitaxel were formulated. The release profile of paclitaxel was then
      manipulated to maximize its biological impact in the in vivo situation. In vitro
      experiments were performed to confirm that the paclitaxel released from the
      polymer was biologically active against cell types that were similar to those
      present in the in vivo lesion of neointimal hyperplasia. Our results demonstrate
      that the paclitaxel polymer wraps which we have developed are mechanically stable
      with a burst release phase followed by a slower continuous release phase. The
      paclitaxel released from these polymeric wraps retains its physicochemical and
      biological properties and is able to inhibit the proliferation of smooth muscle
      cells, endothelial cells and fibroblasts in vitro. We believe that these
      paclitaxel-loaded polymeric wraps could be ideally suited for perivascular drug
      delivery in the context of dialysis access grafts and fistulae.

PMID- 16465050
TI  - Accessory mitral valve tissue: report of two asymptomatic cases.
AB  - Accessory mitral valve tissue is a rare anomaly of embryologic development of the
      endocardial cushion and may cause substantial and progressive obstruction of the
      left ventricular outflow tract. Subaortic obstruction resulting from accessory
      mitral tissue is most likely due to systolic ballooning of the tissue into the
      outflow tract. The obstruction can occur in the early period of life as a result
      of mass effect or it can develop gradually due to the continued deposition of
      fibrous tissues within the left ventricular outflow tract. In patients with
      accessory mitral valve tissue, surgery is mandatory if there is a significant
      obstruction in the left ventricular outflow tract. We report two cases with
      accessory mitral valve tissue causing mild subaortic stenoses which did not
      require surgery.

PMID- 16465051
TI  - Identification of factorial structure of MMSE based on elderly cognitive destiny:
      the Italian Longitudinal Study on Aging.
AB  - The Mini-Mental State Examination (MMSE) is one of the most commonly used
      instruments in the evaluation of global cognitive status, but only few studies
      have investigated the relationship among its components in terms of factorial
      structure. We have considered data from the Italian Longitudinal Study on Aging
      (ILSA), carried out in Italy in 1992 on a sample of 5,632 subjects aged 65-84
      years, and followed up in 1996. The aim of our study was to investigate static
      factorial structure in three groups of elderly (subjects with a diagnosis of
      dementia at baseline; subjects free of dementia at baseline, but incident cases
      at follow-up; subjects who never developed dementia during the 4-year follow-up).
      Considering our results, we could hypothesize that MMSE static structure reflects
      the cognitive profile of elderly, and is thus influenced by subjects' potential
      to develop dementia.

PMID- 16465052
TI  - Prevalence and persistence of mild cognitive impairment among elderly patients in
      general hospitals.
AB  - The aim of the present study was to determine the prevalence of mild cognitive
      impairment (MCI) in elderly patients in general hospitals and to investigate the
      persistence of the cognitive deficits after discharge from the hospital. In a
      sample consisting of 794 non-demented patients in general hospitals aged 65-85
      years, we found an MCI prevalence of 36.1%. The positive predictive value for
      cognitive impairment 3.5 months after hospital discharge was 61.0%. The deficits
      in multiple-domain MCI proved to be particularly stable with a positive
      predictive value of 82.9%. Elderly patients in general hospitals represent a high
      risk group for MCI. These results indicate that general hospitals offer an
      opportunity for the early detection of incipient dementia.

PMID- 16465053
TI  - Identifying patients at high and low risk of cognitive decline using Rey Auditory
      Verbal Learning Test among middle-aged memory clinic outpatients.
AB  - OBJECTIVES: To investigate whether application of cutoff levels in an episodic
      memory test (Rey Auditory Verbal Learning Test, RAVLT) is a useful method for
      identifying patients at high and low risk of cognitive decline and subsequent
      dementia. METHODS: 224 patients with memory complaints (mean age = 60.7 years,
      mean MMSE = 28.2) followed-up at a memory clinic over approximately 3 years were
      assigned retrospectively to one of three memory groups from their baseline
      results in RAVLT [severe (SIM), moderate (MIM) or no impairment (NIM)]. These
      groups were investigated regarding cognitive decline. RESULTS: Patients assigned
      to SIM showed significant cognitive decline and progressed to dementia at a high
      rate, while a normal performance in RAVLT at baseline (NIM) predicted normal
      cognition after 3 years. Patients with MIM constituted a heterogeneous group;
      some patients deteriorated cognitively, while the majority remained stable or
      improved. CONCLUSIONS: The application of cutoff levels in RAVLT at baseline
      showed that patients with severely impaired RAVLT performance were at a high risk
      of cognitive decline and progression to dementia, while patients with normal
      RAVLT results did not show cognitive decline during 3 years. Furthermore, the
      initial degree of memory impairment was decisive in the cognitive prognosis 3
      years later.

PMID- 16465054
TI  - A longitudinal study of quantitative and qualitative features of category verbal
      fluency in incident Alzheimer's disease subjects: results from the PAQUID study.
AB  - Category fluency tests were administered at baseline and after 3 and 5 years on
      two subgroups of subjects from a population-based cohort of elderly subjects: 52
      cases of incident possible and probable Alzheimer's disease (AD) and 104 age- and
      education-matched subjects who remained nondemented. Quantitative and qualitative
      features of category fluency were assessed to determine how changes occur within
      5 years of the diagnosis of AD. Consistent with previous results, we found that
      the number of words produced on this task was already significantly lower 5 years
      before the diagnosis in subjects with incident AD as compared with subjects who
      did not become demented. However, the rate of repetitions only significantly
      increased in AD subjects at the time of diagnosis, and the rate of intrusions
      remained low and not significantly different between the two groups. Thus, it is
      concluded that dysfunction in cognitive processes underlying repetitions and
      intrusions in verbal fluency tasks, such as inhibitory processes and working
      memory, may not be the main cause of the very early deficit in verbal fluency
      occurring in AD.

PMID- 16465055
TI  - The effects of L-arginine on neurological function, histopathology, and
      expression of hypoxia-inducible factor-1 alpha following spinal cord ischemia in
      rats.
AB  - The aim of this study was to investigate the effects of L-arginine (L-Arg) on
      neurological function, histopathology, and expression of hypoxia-inducible factor
      1 alpha (HIF-1alpha) following spinal cord ischemia in rats, and the interaction
      between therapy with the nitric oxide donor L-Arg and up-regulation of the
      expression of HIF-1alpha. Thirty Wistar rats weighing between 200 and 250 g were
      divided into three groups, each containing 10 rats: group 1, sham operation;
      group 2, untreated ischemia-reperfusion (I-R); group 3, I-R plus L-Arg treatment.
      Spinal cord ischemia was applied for 20 min. There were no significant
      differences in mean arterial pressures, temperatures, and blood gas levels among
      the groups. In group 2, malondialdehyde values were significantly increased
      compared with groups 1 and 3. The rats with aortic occlusion in group 2 had
      paraplegia or paraparesis. In group 3, all animals were neurologically intact. In
      group 3, spinal motor neurons did not decrease significantly, and little
      proliferation of microglia was observed compared with those in group 2. In group
      2, spinal motor neurons in ventral gray matter decreased significantly compared
      with those in groups 1 and 3. HIF-1alpha-positive immunostaining was mildly
      detected in group 2 animals. The expression of immunoreactive cells was intensely
      increased in spinal cord tissue from I-R/L-Arg rats. In conclusion, our findings
      suggest that HIF-1alpha-positive immunostaining may be critical factors in the
      pathophysiology of inflammatory spinal cord injury induced by I-R. Nitric oxide
      may play an important role in the immunohistochemical expression of these
      molecules, and the neuroprotective benefit of L-Arg may be attributed to
      preventing neural cell necrosis.

PMID- 16465056
TI  - Changes in hemodynamics and acid-base balance during cross-clamping of the
      descending thoracic aorta. A study in patients operated on for thoracic and
      thoracoabdominal aortic aneurysm.
AB  - AIM OF THE STUDY: In the clinical situation there is discrepancy between various
      investigations regarding the cardiac response of thoracic aortic cross-clamping.
      The aim was therefore to investigate the hemodynamic response and blood gases
      during proximal aortic cross-clamping (XC) in patients operated for descending
      thoracic and thoracoabdominal aortic aneurysm without circulatory support.
      PATIENTS AND METHODS: Altogether 51 patients operated on for thoracoabdominal
      (n=31) or descending thoracic aortic aneurysm (n=20) were included in the
      investigation. All patients were operated with aortic XC, but no circulatory
      support was applied. Hemodynamic variables and blood gases were recorded before
      and during XC. RESULTS: A significant increase in cardiac output during XC from
      4.7 to 6.0 liters/min was observed (p<0.01). There was a similar percentual
      increase in heart rate and also the proximal systolic blood pressure increased. A
      metabolic acidosis occurred during XC. CONCLUSION: Cardiac output was
      significantly increased during XC in patients operated on for thoracoabdominal or
      descending thoracic aneurysm using direct aortic XC without circulatory support.
      Simultaneously, the heart rate was increased and there was a hyperdynamic
      circulatory state proximal to the aortic clamp. Redistribution of the blood
      volume in addition to catecholamine release may be responsible for the observed
      changes. These observations may influence the selection of operative strategy for
      some of these patients.

PMID- 16465057
TI  - Hyperperfusion syndrome in small-for-size livers.
AB  - BACKGROUND: Portal hyperperfusion in small-for-size livers might seriously impair
      postoperative liver regeneration. Using an experimental model, we investigated
      splenectomy as a measure to reduce portal blood flow and its impact on
      postoperative recovery following extended liver resection. METHOD: Wistar rats
      underwent partial (90%) hepatectomy with or without splenectomy under temporary
      inflow occlusion (30 min). In addition to 10-day survival rate, laser Doppler
      flowmetry of hepatic blood flow and fluorescence microscopic analysis of hepatic
      microcirculation were performed to assess the effect of splenectomy on initial
      microvascular reperfusion of liver remnants. RESULTS: While postischemic
      perfusion failure was comparable between both groups, portal blood flow was
      significantly reduced after simultaneous splenectomy (3.5+/-0.4 vs. 5.4+/-0.4
      ml/min). Moreover, red blood cell velocity and volumetric blood flow were reduced
      in splenectomized animals. These animals experienced lower AST levels (421+/-36
      vs. 574+/-73 U/l) and a significantly increased survival rate, reaching 6.6+/-1.3
      vs 2.6+/-0.8 days. CONCLUSION: Simultaneous splenectomy significantly reduced the
      risk for postoperative hyperperfusion syndrome in small-for-size livers. Shear
      stress-induced liver injury was diminished due to a significant reduction of
      portal venous blood flow, which positively influenced postoperative regeneration
      resulting in significantly higher survival.

PMID- 16465058
TI  - Glutamine improves intestinal barrier function in experimental biliary
      obstruction.
AB  - OBJECTIVE: To determine the effects of enteral administration of glutamine on
      intestinal barrier function in experimental biliary obstruction. BACKGROUND:
      Extrahepatic biliary obstruction is associated with the failure of intestinal
      barrier function, allowing bacteria and other substances from the intestine to
      enter the circulation and initiate a systemic inflammatory response, causing
      impairment of multiple organs. The amino acid glutamine has been shown to improve
      intestinal barrier function in other conditions, but its effects in biliary
      obstruction have not been fully examined. METHODS: This study examined the
      effects of enteral administration of glutamine on intestinal permeability and on
      bacterial translocation from the intestine in a rodent model of biliary
      obstruction. RESULTS: Glutamine was shown to reduce intestinal permeability
      measured as percentage excretion of 14C 7 days after biliary obstruction (0.35+/
      0.03 vs. 0.56+/-0.085% in controls, p=0.028), and glutamine administration was
      also associated with a decreased incidence of bacterial translocation to extra
      intestinal sites (p=0.03). Radiolabelled bacterial studies also demonstrated
      reduced translocation of bacterial fragments to extra-intestinal sites in
      glutamine-treated animals (p=0.01). There was also some evidence of decreased
      exposure to endotoxin, reduced systemic inflammation and increased bacterial
      killing by the immune system in glutamine-treated animals. CONCLUSIONS: Glutamine
      modulates intestinal permeability and reduces bacterial translocation in an
      animal model of experimental biliary obstruction and may increase bacterial
      killing by the immune system.

PMID- 16465059
TI  - Mild hypothermia ameliorates lung ischemia reperfusion injury in an ex vivo rat
      lung model.
AB  - BACKGROUND: Ischemia reperfusion (I-R) injury of the lung frequently occurs after
      cardiopulmonary bypass, pulmonary thromboendarterectomy, lung transplantation,
      and major pulmonary resection with vascular reconstruction. Mild hypothermia
      ameliorates ischemia reperfusion injury of the brain and the liver. However, the
      effect of mild hypothermia on I-R injury of the lung has not been investigated.
      METHODS: The lungs of Lewis rats underwent 80 min of ischemia followed by 60 min
      of reperfusion in an ex vivo perfusion model. The ambient temperature was
      maintained at either normothermia (38 degrees C, n=6) or mild hypothermia (35
      degrees C, n=6) during the ischemia and reperfusion. RESULTS: Pulmonary shunt
      fraction, peak inspiratory pressure, mean pulmonary arterial pressure during
      reperfusion, and the wet/dry weight ratio of the lung tissue at the end of
      reperfusion in the mild hypothermia group were significantly (p<0.05) lower than
      those in the normothermia group. Total adenine nucleotide, adenosine
      triphosphate, adenosine diphosphate, and adenosine monophosphate after
      reperfusion in the mild hypothermia group were significantly (p<0.05) higher than
      those in the normothermia group. CONCLUSION: Mild hypothermia attenuates I-R
      injury of the lung with maintained levels of intrapulmonary high-energy phosphate
      compounds after reperfusion, suggesting its beneficial effect on warm lung I-R in
      clinical settings.

PMID- 16465060
TI  - Ghrelin and leptin elevation in postoperative intra-abdominal sepsis.
AB  - BACKGROUND: Both ghrelin and leptin are important signals in the regulation of
      food intake and energy balance. Leptin concentrations are elevated in the
      majority of obese individuals, and its levels usually correlate with adiposity
      and body mass index. Ghrelin as a new growth hormone (GH)-releasing peptide was
      discovered in 1999. Ghrelin stimulates food intake and exhibits gastroprotective
      properties. Many other regulatory effects of both ghrelin and leptin involving
      cardiovascular, gastrointestinal, renal, and endocrine systems were revealed. New
      experimental studies show both hormones as new acute phase reactants in animal
      models of inflammatory reaction. The aim of this study was to characterize the
      levels of circulating ghrelin and leptin in relation to systemic inflammatory
      response. We used a postoperative bacterial sepsis after large abdominal surgery
      as a model of cytokine network hyperstimulation. PATIENTS AND METHODS: The
      prospective study was performed on 25 surgical patients with proven postoperative
      intra-abdominal sepsis after large abdominal surgery. Plasma levels of ghrelin
      (RIA), leptin, TNF-alpha, IL-1beta, sIL-2R, IL-6 (ELISA analysis), CRP and alpha1
      antitrypsin (nephelometric analysis) were analyzed. RESULTS: Authors demonstrate
      statistically significant elevation of plasma ghrelin (492.3+/-70.6 ng/l) and
      leptin (31.6+/-12.2 microg/l) compared with the control group (336.5+/-46,1,
      p<0.01 for ghrelin, 3.5+/-1.2 microg/l, p<0.001 for leptin). The regression
      coefficient was the highest for ghrelin and IL-6 (r=0,44, p<0.05), and for
      ghrelin and TNF (r=0.43, p<0.05) in the sepsis group. In regard to leptin, the
      regression coefficient was the highest for IL-6 and leptin (r=0.53, p<0.05) and
      for leptin and CRP (r=0.51, p<0.05). There was no significant correlation between
      ghrelin and IL-1beta, ghrelin and sIL-2R, and leptin and IL-1beta. CONCLUSIONS:
      During postoperative intra-abdominal sepsis, both ghrelin and leptin plasma
      levels are elevated and positively correlate with both inflammatory cytokines
      (TNF-alpha, IL-6) and main APP member (CRP). It supports experimental finding
      that TNF-alpha and IL-6 can be important regulatory factors of their synthesis.
      This hormonal reaction is not specific to sepsis--the significant increase of
      both ghrelin and leptin occurs during an uncomplicated postoperative response,
      although in a lesser extent than was shown in sepsis.

PMID- 16465061
TI  - Relation between severity of injury and the early activation of interleukins in
      multiple-injured patients.
AB  - The aim of this study was to evaluate the relation between severity of injury and
      the early activation of interleukins in multiple-injured patients. Ninety-nine
      patients with multiple injuries were included in this prospective study. Plasma
      levels of interleukin (IL)-1, IL-2, IL-6, IL-8 and TNF-alpha were measured.
      Injury Severity Score (ISS), Revised Trauma Score (RTS), Glasgow Coma Score (GCS)
      and the Acute Physiology and Chronic Health Evaluation II (APACHE-II) were all
      recorded. Of the 99 patients, 82 were male and 17 were female. The mean age was
      26.6+/-20.7 years. The mortality rate for this series was 17%. Patients who died
      from trauma exhibited a significant increase for IL-2, IL-6 and IL-8 in
      comparison with patients who survived. Significant differences for ISS, RTS and
      GCS were found between survivors and non-survivors. Values in all patients with
      ISS>16 were increased and these increases were significant for IL-6 and IL-2.
      These data show that the initial increase of IL-2, IL-6 and IL-8 might predict
      the patients with a high possibility of mortality and a significant increase of
      IL-2 and IL-6 in patients with ISS>16 might be used in a new developed trauma
      score combined with ISS as an indicator for the injury severity.

PMID- 16465062
TI  - Extended liver resection and hepatic ischemia in pigs: a new, potentially
      reversible model to induce acute liver failure and study artificial liver support
      systems.
AB  - BACKGROUND: Extended hepatectomy is a valid model for the study of acute liver
      failure. Since the porcine liver is comparable in size, morphology and anatomy to
      the human liver, we describe a technique employing hepatic ischemia and extended
      liver resection to induce acute liver failure in a porcine model as a means of
      studying bioartificial liver support. METHOD: A subtotal (75-80% resection)
      extended left hepatectomy was performed in 7 pigs after 60 min warm ischemia of
      the future remnant liver. After resection, the animals were given the best
      supportive care and observed until death. RESULTS: All animals died within 18-48
      h, none as a result of surgical complications. Gross appearance of the liver
      showed severe steatosis of the right lateral lobe, and histology revealed severe
      coagulative necrosis of the whole lobule. CONCLUSION: This technique of extended
      liver resection after hepatic ischemia in the porcine model may be useful for
      studies of potentially reversible acute liver failure and experimental
      bioartificial support.

PMID- 16465063
TI  - HMG-CoA reductase inhibitors reduce matrix metalloproteinase-9 activity in human
      varicose veins.
AB  - Matrix metalloproteinases (MMPs) have been implicated in tissue degradation in
      varicose veins. The aim of this study was to investigate the effects of 3-hydroxy
      3-methylglutaryl coenzyme A reductase inhibitors (statins) on the activity of
      MMPs in varicose veins. MMP-9 was present at significantly higher levels in
      varicose veins than in controls and was localized mainly in smooth muscle cells
      at the tunica media, where marked degradation of the extracellular matrix was
      observed. Both simvastatin and pravastatin strikingly suppressed MMP-9 activity
      in ex vivo culture of varicose veins. Simvastatin suppressed MMP-9 at both the
      mRNA and protein levels as well as at the urokinase-type plasminogen activator
      protein level, resulting in the dramatic suppression of MMP-9 activity induced by
      tumor necrosis factor-alpha. Therefore, statins suppress MMP-9 activity by
      multiple mechanisms in varicose veins, suggesting they may have clinical
      potential for the treatment of this disease.

PMID- 16465064
TI  - Age is not a limiting factor for midurethral sling procedures in the elderly with
      urinary incontinence.
AB  - OBJECTIVE: The object was to evaluate clinical outcome of the midurethral sling
      procedures in the elderly compared with middle-aged women. METHODS: A total of
      266 women who underwent midurethral sling procedures with at least follow-up
      greater than 6 months were included in the study. Patients were divided as the
      elderly group (65 years old or older, n = 60) and the middle-aged group (45-64
      years old, n = 206). RESULTS: Although postoperative urge symptoms were more
      prevalent in the elderly group (25.0%) than in the middle-aged group (6.3%),
      there were no significant differences between the two groups for the rates of
      postoperative urge incontinence (p = 0.159). Stress incontinence was cured by
      91.3% in the middle-aged group and 85.0% in the elderly group, respectively (p =
      0.158). CONCLUSIONS: Age does not seem to be a significant risk factor for
      failure of midurethral sling procedures.

PMID- 16465065
TI  - From East to West: patterns of genetic diversity of populations living in four
      Eurasian regions.
AB  - We have analyzed the distribution and patterns of the genetic diversity of eight
      Alu loci (ACE, ApoA1, PV92, TPA25, NBC27, NBC102, NBC148, and NBC182) in 1,049
      individuals representing 16 populations of the Volga-Ural region (Bashkirs,
      Tatars, Komis, Maris, Mordvins, and Udmurts), Central Asia (Kazakhs, Uzbeks, and
      Uighurs), the North Caucasus (Karachays, Kumyks, Kuban Nogays, and Karanogays),
      and Central South Siberia (Yakuts, Kalmyks and Evenks). Geographic divide between
      Europe and Asia, e.g. the Ural Mountains and the Caspian Sea, can also be
      considered as a genetic boundary. The data indicates that the populations of the
      two boundary regions between Europe and Asia, the Volga-Ural region of Russia,
      and populations of the North Caucasus are more similar to European than to Asian
      populations. Finally, Siberian and Central Asian populations are genetically
      closely related to each other.

PMID- 16465066
TI  - Burden of pancreatic cancer and disease progression: economic analysis in the US.
AB  - OBJECTIVES: The few studies that have estimated the costs of pancreatic cancer
      were limited by small sample sizes, geography or patient age range. Using a large
      nationwide claims database, this study examines the cost of pancreatic cancer
      beginning with initial diagnosis and the additional costs when disease
      progresses. METHODS: A retrospective cohort study was conducted using a claims
      database of 3 million individuals covered by large US employers. The study
      population consisted of patients newly diagnosed with pancreatic cancer in 1999
      2000 and a demographically matched control group. Utilization and costs were
      summarized as monthly means. Changes in cancer severity and treatment over time
      were used to approximate disease progression and its associated costs. RESULTS:
      The study included 412 pancreatic cancer patients and 1,236 controls. The mean
      follow-up time was 7.5 months. Regression-adjusted monthly costs attributable to
      pancreatic cancer were USD 7,279; over 60% resulted from hospitalizations.
      Patients with disease progression (over 50%) incurred an additional USD 15,143
      per month compared to patients without disease progression. CONCLUSION: Compared
      to patients without cancer, the costs of pancreatic cancer patients were
      substantial, especially when patients experienced disease progression. New
      therapies that prevent or delay disease progression could potentially offset the
      costs to patients, providers and society.

PMID- 16465068
TI  - Fatty acid cytotoxicity to organ-cultured bovine lenses.
AB  - High sensitivity of cultured bovine and human lens epithelial cells to
      unsaturated free fatty acids has been reported in previous papers. Here we show
      that micromolar concentrations of unsaturated free fatty acids also impair lens
      cells during organ culturing, a system which resembles the in vivo situation much
      better than cell cultures do. This added weight to the assumption that fatty acid
      cytotoxicity might be causally related to senile cataract as well as to cataracts
      associated with systemic diseases.

PMID- 16465069
TI  - The influence of mastoidectomy on natural history of secretory otitis media in
      cochlear implant children.
AB  - Secretory otitis media (SOM) is a common childhood disease. The goal of the
      present study was to determine the influence of mastoidectomy on the incidence of
      postimplantation SOM in cochlear implant children. We conducted a retrospective
      study of all the children up to the age of 8 years, who underwent cochlear
      implantation from 1993 to 2001 in our department. The children were divided into
      two groups according to the surgical technique used for the implantation: 94
      children underwent implantation with the posterior tympanotomy approach
      (including mastoidectomy) and 48 children were implanted with a suprameatal
      approach (without mastoidectomy). The incidence of SOM before and after the
      implantation was compared between the two groups. There were no significant
      differences between the two study groups in terms of age and the pre- and
      postimplantation incidence of SOM. Mastoidectomy failed to demonstrate any
      influence on the natural history of SOM.

PMID- 16465070
TI  - Validation of ultrasonography to evaluate murine orthotopic oral cavity tumors.
AB  - BACKGROUND: The murine orthotopic oral cavity tumor model allows evaluation of
      tumor growth and invasion. Currently, serial measurements of tissue growth are
      difficult to obtain since invasive procedures or animal sacrifice is necessary to
      evaluate tumor size. High-resolution ultrasound was evaluated as a noninvasive
      method to monitor tumor size in vivo. METHODS: Sixteen immunodeficient mice, age
      9 weeks, were injected transcervically with a human squamous cell carcinoma cell
      line into the tongue, and tumor volume was assessed by high-frequency ultrasound
      at 11 days. The animals were subsequently sacrificed and the tumors processed for
      histology. Tumor size was then calculated by caliper measurement in two
      dimensions. RESULTS: Tumor dimensions obtained using ultrasound were found to
      significantly correlate with the histologic measurements (Spearman coefficient
      0.90, p < 0.0001). Tumor dimensions were on average larger using ultrasound
      versus histologic measurements, although this was not significantly different
      than zero (95% confidence interval -13.96 to 62.37 mm2). CONCLUSIONS: High
      resolution ultrasound accurately measures tumor volume in the murine orthotopic
      oral cavity tumor model without sacrifice.

PMID- 16465071
TI  - Autologous fat augmentation for voice and swallow improvement after cordectomy.
AB  - Surgery for the treatment of early-stage glottic carcinoma still remains a valid
      option. In most patients, newly formed neocord tissue preserves glottic
      functions, but in some patients an important glottic gap leading to glottic
      insufficiency may occur. In our study, 11 patients who had serious glottic
      insufficiency after endoscopic laser and laryngofissure cordectomy were treated
      with autologous fat injection (AFI) into the neocord tissue for voice and
      swallowing rehabilitation. One patient did not attend the first control visit and
      was excluded from the study. The remaining 10 patients were evaluated in the
      preoperative and postoperative periods for phonatory functions and efficacy of
      AFI by videolaryngostroboscopy and computerized acoustic analysis. Phonatory
      functions showed statistically significant improvement in the shimmer, noise-to
      harmonic ratio, maximum phonation time and fundamental frequency. Perceptual
      ratings (GRBAS scale) also showed statistically significant improvement in all 5
      parameters. Despite improvement in glottic closure, the mucosal wave
      deteriorated. Due to recurrence of symptoms of glottic insufficiency, AFI was
      repeated in 2 patients at the third and fifth months, respectively. One year
      later, the AFI resulted in successful rehabilitation of swallowing in all
      patients. The probability of resorption of autologous fat and the deterioration
      of the mucosal wave after AFI remain a problem, but re-injection can be done
      easily. As AFI is an easy, safe and cheap method, we concluded that it is a
      promising alternative procedure for managing voice problems after laser or
      laryngofissure cordectomy defects.

PMID- 16465072
TI  - Effect of corticosteroids or diuretics in low-tone sensorineural hearing loss.
AB  - OBJECTIVES: We retrospectively analyzed 225 patients with acute low-tone
      sensorineural hearing loss (ALSHL), comparing the effectiveness of corticosteroid
      and diuretic therapy, and also determining the factors affecting hearing
      recovery. DESIGN: Retrospective clinical record review. METHODS: Multivariate
      logistic regression analysis. RESULTS: Analyses identified unfavorable factors
      such as aging, late initiation of treatment, and pretreatment pure-tone hearing
      thresholds at three lower frequencies adding up to 95 dB and more. Multivariate
      logistic regression analysis indicated a significantly greater improvement in
      hearing in patients treated with corticosteroids at high initial and total doses
      than in those treated with vitamin B12 and ATP without adding corticosteroids. In
      145 patients treated with corticosteroids, multivariate logistic regression
      analysis showed a trend toward greater improvement with high initial and total
      doses than with low doses. CONCLUSION: Corticosteroids should be changed from low
      to high doses within 7 days after onset of ALSHL, if low doses are failing.

PMID- 16465073
TI  - Molecular assessment of neck dissections supports preserving level IIB lymph
      nodes in selective neck dissection for laryngeal squamous cell carcinoma with a
      clinically negative neck.
AB  - OBJECTIVES: It was the aim of this study to determine whether level IIB lymph
      nodes can be saved in elective neck dissection as a treatment for patients with
      squamous cell carcinoma (SCC) of the larynx. We present a prospective analysis of
      a case series. METHODS: Thirty-one patients with SCC of the larynx and without
      palpable lymph nodes at the neck who underwent an elective neck dissection were
      prospectively studied. The incidence of micrometastasis to level IIB lymph nodes
      after performing elective neck dissection was evaluated by nested reverse
      transcription polymerase chain reaction for cytokeratin (CK)19 and CK20 as well
      as by pathological examination. RESULTS: Nested reverse transcription polymerase
      chain reaction for CK19 and CK20 mRNA presented similar results but differed from
      the pathological examination. Of the 31 patients, 6 (19%) by pathological
      analysis and 9 (29%) by molecular analysis had lymph nodes positive for
      metastatic SCC. By molecular analysis, only 1 of the 31 patients had involvement
      of level IIB lymph nodes. CONCLUSIONS: This region may be preserved in elective
      neck dissection in patients with SCC of the larynx, so that accessory nerve
      dysfunction can be minimized and operative time can be saved.

PMID- 16465074
TI  - Survival analysis of children with primary malignant brain tumors in England and
      Wales: a population-based study.
AB  - Primary malignant brain tumor is the second most common cancer in children. To
      investigate factors affecting children's survival at a population level, data of
      3,169 patients (age<15 years) from the Cancer Registry in England and Wales were
      used. They were diagnosed during 1971-1990 and followed up until 1995. Variables
      including age, gender, morphology, WHO grade, tumor site, socioeconomic status,
      geographical region, and period of diagnosis were available for analysis using
      the Kaplan-Meier method and the Cox hazards ratio (HR) regression. Results showed
      that the median survival and the 1-, 5-, and 10-year crude survival rate for this
      population were 8.7 years, 72.4, 54.0, and 49.2% respectively. Survival was
      influenced by age (HR 0.88/5 years), morphology (ependymoma HR 2.43), WHO grades
      (HR 1.42/grade), tumor sites (brain stem HR 2.11), and periods of diagnosis (HR
      0.88/5 years). Gender, socioeconomic status, and geographical region did not
      affect their survival. Results from this population-based data are very helpful
      for comparison with other hospital-based studies and for public health purposes.

PMID- 16465075
TI  - Intraoperative portable 0.12-tesla MRI in pediatric neurosurgery.
AB  - OBJECTIVES: Intraoperative MRI (iMRI) is used mainly in the adult neurosurgical
      population. The main indications for iMRI usage are resection control and updated
      intraoperative navigation capabilities. In this paper we present our experience
      using this technique in children. Specific advantages of iMRI for this age group
      are discussed. METHODS AND RESULTS: We retrospectively reviewed 31 pediatric
      neurosurgical procedures in which a portable iMRI system was used. The
      indications for iMRI usage were preoperative navigation, resection control during
      tumor removal, shunt placements, and needle biopsy. In 7 children the use of the
      iMRI changed the course of the surgical procedure. Operative morbidity and
      mortality were not increased with use of the iMRI. CONCLUSIONS: iMRI systems have
      advantages for the pediatric neurosurgical population, including both real-time
      basic navigation and improved resection control.

PMID- 16465076
TI  - Stereotactic radiation therapy with chemotherapy in the management of recurrent
      medulloblastomas.
AB  - Medulloblastomas are highly lethal tumors when they recur. Very few patients
      survive with conventional treatment. This report documents the preliminary study
      results of a treatment for recurrent medulloblastomas consisting of stereotactic
      radiation therapy (SRT) with chemotherapy. Four patients had local recurrence
      without apparent metastases and 8 patients had metastases with or without local
      recurrence. Twelve patients with 18 lesions underwent SRT as a single session
      (n=8) or in a hypofractionated manner (n=10) using a gamma knife or modified
      linear accelerator. All patients then received systemic chemotherapy. Five
      patients were treated with one to two sequential courses of high-dose
      chemotherapy with peripheral blood stem cell transplantation. The reduction in
      tumor size after SRT was often remarkable. Fourteen of 18 lesions treated
      disappeared 1-6 months after SRT. Two of 4 patients who had local recurrences
      without apparent metastasis at the time of SRT are alive without evidence of
      disease 70 and 72 months after SRT, respectively. In contrast, all 8 patients
      with metastasis had new lesions either in the spinal canal or on the surface of
      the brain outside the target area of SRT. Median progression-free survival and
      overall survival from the time of SRT were 9 and 19 months, respectively. The
      Kaplan-Meier estimates of PFS and overall survival at 3 years were 17 and 25%,
      respectively. One patient had brainstem edema after SRT causing bulbar palsy and
      quadriparesis. One patient died of toxicity of chemotherapy. Our experience
      suggests that local recurrence can be controlled by SRT with chemotherapy but
      survival of patients with metastases can not be improved effectively by SRT in
      conjunction with aggressive chemotherapy.

PMID- 16465077
TI  - Central nervous system tumors in patients under three years of age: treatment
      results of a single institute.
AB  - Eighty-six patients under 3 years of age with central nervous system tumors were
      retrospectively analyzed between 1972 and 2003. Surgical resection was done in
      all patients except for those with optic glioma, pons glioma and pineal tumor.
      Three different chemotherapy regimens were used in different time periods. In 48
      patients, the tumor was located in the posterior fossa, and 29 patients had a
      supratentorial tumor. We had 32 (37.2%) patients with embryonic tumors (21
      medulloblastoma, 4 ependymoblastoma, 5 with atypical teratoid rhabdoid and 2 with
      supratentorial primitive neuroectodermal tumors), 21 (24.4%) with ependymoma, 14
      (16.3%) with optic glioma, 10 (11.6%) with astrocytoma, 3 (3.5%) with pons glioma
      and 6 (7.0%) with others. Overall (OS) and event-free survival rates were 49.5
      and 40.9%. OS rates according to the tumor localizations were 40.9 and 68.1% in
      the posterior fossa and supratentorial localizations, respectively (p=0.001). OS
      rates were 33.7, 41.3 and 88.8% for the medulloblastoma+primitive neuroectodermal
      tumor groups, ependymoma and astrocytoma, respectively (p=0.0001). Most of the
      patients had primitive embryonic tumors (37.2%). The best prognostic factors were
      tumor localization and histology.

PMID- 16465078
TI  - Risk of ventriculoperitoneal shunt infections due to gastrostomy feeding tube
      insertion in pediatric patients with brain tumors.
AB  - OBJECTIVE: To determine the risk of ventriculoperitoneal (VP) shunt infections
      after percutaneous retrograde gastrostomy feeding tube (GT) placement in children
      with brain tumors. PATIENTS AND METHODS: All children (age 0-18 years) with
      primary brain tumors diagnosed and treated at the Hospital for Sick Children,
      Toronto, Canada, were subjected to a retrospective analysis. Two groups were
      identified: the study group included children with a VP shunt and a GT; the
      control group included children with VP shunts only. Each study patient was
      matched with 2 controls to compare the rate of infections (cohort comparative
      study). RESULTS: There were 1,167 children diagnosed and treated with primary
      brain tumors during the study period (1988-2003); 174 (15%) had a VP shunt and 23
      (2%) children had both, a VP shunt and a GT. In the study group (n=17), GTs were
      inserted at a median time of 80 days (range 6-204 days) after VP shunts. VP shunt
      infection rate was 23.5% (4/17) compared to 8.8% (3/34) in the control group (OR
      3.18; 95% CI 0.622-16.54, p=0.16). Three (75%) of the infection episodes in the
      study group presented with an ascending VP shunt infection directly related to
      the GT insertion or manipulation in the first 6 weeks. These GTs were inserted at
      13, 47 and 49 days after VP shunt insertion. CONCLUSION: Placement of
      percutaneous retrograde GTs, in the acute phase, in children with brain tumors
      and VP shunts may increase the risk of ascending meningitis especially if there
      are early GT-related complications.

PMID- 16465079
TI  - Case report of optic atrophy in pansynostosis: an unusual presentation of scalp
      edema from hair braiding.
AB  - Pansynostosis (fusion of all cranial sutures) and optic atrophy were found as
      incidental CT scan and ophthalmological findings in an 8-year-old who presented
      to the emergency room with scalp edema from tight 'cornrow' hair braiding.
      Cranial vault expansion was successfully performed. Ophthalmological problems
      have stabilized but have not reversed. Late presentation of craniosynostosis and
      the pathophysiology of secondary optic atrophy are discussed.

PMID- 16465080
TI  - Endoscopic resection of an intraventricular dysembryoplastic neuroepithelial
      tumor of the septum pellucidum.
AB  - Tumors located in the region of the foramen of Monro often present with signs and
      symptoms of obstructive hydrocephalus. Various types of lesions occur in this
      location. We describe a case of a dysembryoplastic neuroepithelial tumor of the
      septum pellucidum presenting with obstructive hydrocephalus and its successful
      endoscopic excision. The surgical considerations and pathologic findings are
      discussed.

PMID- 16465081
TI  - Syndromic craniosynostosis with elbow joint contracture.
AB  - This paper reports a new type of syndromic craniosynostosis that was diagnosed by
      DNA analysis of the patient's fibroblast growth factor receptor (FGFR) genes. At
      birth, a male infant had ocular proptosis, a pseudotail, and obstructed
      respiration. He developed craniosynostosis, craniofacial dysmorphism,
      hydrocephalus, and bilateral contracture of his elbow joints. His treatment
      included fronto-orbital advancements and a ventriculoperitoneal shunt. Genetic
      analysis revealed that he was heterozygous for a missense mutation in exon 9 of
      the FGFR2 gene that resulted in an amino acid substitution of cysteine for serine
      at residue 351 (Ser351Cys). Seven cases with this mutation had previously been
      reported. All had severe craniosynostosis with midface hypoplasia, elbow joint
      contracture, developmental retardation, and early death.

PMID- 16465083
TI  - Infant with unusually large choroid plexus papilloma undergoing emergency
      surgery. Case report with special emphasis on the surgical strategy.
AB  - Choroid plexus papillomas are one of the most common tumors of the nervous system
      in infants. The most frequent early symptoms, megalocephalia and vomiting, caused
      by elevated intracranial pressure often lead to a diagnosis only at a critical
      clinical stage. This study describes a case of a 3-month-old infant with a
      choroid plexus papilloma measuring 7 x 8 x 6 cm originating in the right lateral
      ventricle. The infant underwent emergency surgery in an acutely deteriorated
      state, i.e., acute herniation symptoms with fixed and dilated pupils. Despite of
      the size of the tumor, the proximity to eloquent cortex, and clinically
      deteriorated state, the infant recovered completely.

PMID- 16465082
TI  - Complete recovery of spinal cord injury without radiographic abnormality and
      traumatic brachial plexopathy in a young infant falling from a 30-feet-high
      window.
AB  - The laxity and elasticity of the infant or child spine may predispose him to
      cervical spine injury without bony disruption. The term 'SCIWORA' syndrome
      (Spinal Cord Injury Without Radiographic Abnormalities) is commonly used to
      characterize this condition. We report a 14-month-old infant who fell from a
      fourth-story window, with delayed onset of SCIWORA and brachial plexopathy. The
      infant initially presented with complete limb paralysis, but had a full recovery
      6 months later. In contrast to the classical grave prognosis of these two
      conditions, our case represents one of the few exceptions in the literature with
      excellent recovery. Corresponding to previous reports, we suggest that the
      initial normal appearance of the spinal cord and nerve roots on magnetic
      resonance image may serve as a good prognosticator, regardless of the severity of
      initial neuroelectrophysiological studies or clinical manifestations.

PMID- 16465084
TI  - Spontaneous acute subdural hematoma following contralateral calcified chronic
      subdural hematoma surgery: an unusual case.
AB  - Calcified chronic subdural hematoma (CCSDH) is a well-known disease to many
      neurosurgeons but only few cases have been reported regarding its surgical
      complications. We report a spontaneous acute subdural hematoma following
      contralateral CCSDH surgery in a 16-year-old boy and discuss its possible
      mechanisms. The first few days of the postoperative period, especially for the
      cerebral atrophy cases, should be monitored carefully and a control computerized
      tomography scan should be performed early for possible complications. To our
      knowledge, spontaneous acute subdural hematoma following contralateral CCSDH
      surgery has not been reported previously.

PMID- 16465085
TI  - Pott's puffy tumor: a rare complication of mastoiditis.
AB  - Pott's puffy tumor is rarely seen in the modern era of antibiotics. It is usually
      seen as intracranial complication following inappropriately treated frontal
      sinusitis. Up until 2001 there have been only 21 pediatric cases reported in the
      literature and most have been secondary to frontal sinusitis. Only 1 case has
      been reported following a latent mastoiditis and that has been in an adult [1].
      We report a case in a child who developed Pott's puffy tumor following
      mastoiditis.

PMID- 16465086
TI  - Bowel perforation and transanal protrusion of a ventriculoperitoneal shunt
      catheter.

PMID- 16465087
TI  - Rapid increase in volume of multiple tumor cysts after intracranial pressure
      reduction.

PMID- 16465088
TI  - Concerning the article by levine et Al.: 'minimally invasive management of a
      traumatic artery aneurysm resulting from shaken baby syndrome'. Pediatr neurosurg
      2004;40:128-131.

PMID- 16465090
TI  - Geriatric competencies for RNs in hospitals.
AB  - Nurses in staff development are responsible for assuring nurses' competence in
      the delivery of care. Older patients are the predominant population in hospitals,
      yet there are no instruments that specifically assess the competency of nurses to
      deliver care to older patients. This article reports on the development and
      testing of an instrument, Geriatric Competencies for RNs in Hospitals, and makes
      recommendations as to how staff development educators can use the geriatric
      competency instrument with staff nurses.

PMID- 16465091
TI  - The impact of a nurse externship program on the transition process from graduate
      to registered nurse: Part III. recruitment and retention effects.
AB  - This is the third and final part of a series of articles that report the findings
      of a study that investigated the effects of a summer externship program on the
      transition into a professional role among nurses who participated in a summer
      nurse externship program at an acute care pediatric hospital. Specifically, this
      article reports the retention and recruitment benefits of a summer nurse
      externship program for the institution from 1998 through 2003. A total of 153
      externs out of the 193 (79.0%) assumed a registered nurse position at the
      institution, and 77% remained in that role for 12 months. Overall, the nurse
      extern program for this institution appeared to be an effective recruitment and
      retention strategy that is on par with the institution and national data for
      retention and turnover data.

PMID- 16465092
TI  - Clinical Scholar Model: providing excellence in clinical supervision of nursing
      students.
AB  - The Clinical Scholar Model (CSM) is a practice-education partnership focused on
      improving the outcomes of clinical nursing education by bridging the academic and
      service settings. An expert clinical nurse serves as a clinical scholar (CS) to
      coordinate, supervise, and evaluate the clinical education of nursing students in
      collaboration with school of nursing faculty. This article describes the model's
      evolution, how the model is differentiated from traditional clinical instruction
      roles and responsibilities, and the benefits to the collaborating clinical agency
      and school of nursing.

PMID- 16465094
TI  - Nursing education and professional practice: a collaborative approach to enhance
      retention.
AB  - Factors that have led to the current shortage of nurses include a decrease in
      school of nursing enrollments, an aging workforce leading to retirement
      attrition, and a decrease in the numbers of nurses remaining within the
      profession. Compounding the workforce shortage problem, nurses are becoming more
      frustrated with work and their work environment. Negative work environment can
      lead to turnover, or worse still, nurses leaving the profession entirely. The
      purpose of this article is to identify how schools of nursing can work together
      with hospitals to achieve quality educational preparation for graduates, promote
      positive experiences for the student nurse, and assist hospitals with maintaining
      a positive nurse-friendly environment for the nursing staff.

PMID- 16465096
TI  - Evaluation of end-of-life nursing education for continuing education and clinical
      staff development educators.
AB  - This article presents data from the 1-year follow-up of the three conferences
      targeted toward continuing education (CE) providers and staff development (SD)
      educators and reviews the train-the-trainer model used in disseminating the End
      of-Life Nursing Education Consortium (ELNEC) curriculum. The analysis has
      implications for educators to promote improved end-of-life (EOL) care in their
      own institutions.

PMID- 16465105
TI  - The evaluation of mechanical devices for lateral transfers on perceived exertion
      and patient comfort.
AB  - PURPOSE: The purpose of this study was to compare the perceived physical stress
      felt by subjects (nursing and other hospital personnel), time spent, number of
      personnel required, and patient comfort using various methods to transfer
      patients laterally in the supine position. DESIGN: Descriptive comparative
      design. SAMPLE: One hundred ninety-two transfer ratings (132 using manual methods
      and 60 using a mechanical device) were compared. Thirty-two transfers (18 manual
      and 14 mechanical device) were timed, and 39 patients (12 having manual transfer
      and 27 with a mechanical device) provided comfort ratings. FINDINGS: Perceived
      exertion was significantly less for subjects performing lateral transfers with a
      mechanical device than with manual methods. Fewer personnel were needed for
      transfers with mechanical devices. Approximately 5 minutes less per transfer was
      needed when using mechanical devices, and patients felt significantly more
      comfortable and secure when a mechanical transfer device was used. DISCUSSION:
      The use of a mechanical device for transfer provided lower exertion ratings, used
      less personnel and time, and was more comfortable for patients. There are
      barriers to use, however, because of resistance to change, perceived increase in
      time needed for transfer, and the limitation of storing and retrieving the
      devices. Provision of equipment does not ensure use; institution of teaching and
      no-lift policies can facilitate use of lifting/transferring equipment.

PMID- 16465107
TI  - Toe-to-hand transplantation surgery.
AB  - This article discusses toe-to-hand transplantation. The purpose of this article
      is to familiarize nurses with this procedure. In many cases, the actions taken
      initially and postoperatively may have a direct effect on the success or failure
      of the surgery. Two different procedures are discussed. The first procedure is
      replantation or revascularization of amputated digits in which time is of the
      essence and is usually performed right after the initial injury. The second
      procedure is the toe-to-hand transfer, which is an elective procedure in which
      there is less emphasis on time. This procedure occurs a few months after the
      initial accident.

PMID- 16465109
TI  - Physical activity behavior of American Indian mothers.
AB  - BACKGROUND: Mothers of young children who live in low-income households are a
      population at-risk for sedentary living that could experience important health
      benefits from improved physical activity behavior. Previous research among
      Caucasian mothers attending the Women, Infants and Children (WIC) program showed
      that the Transtheoretical Model of behavior change was an appropriate model for
      designing interventions for activity promotion. PURPOSE: This study examined the
      Transtheoretical Model of behavior change in relationship to the physical
      activity behavior of low-income American Indian mothers. DESIGN: A descriptive
      correlational study employed a purposive sample (N = 30) of six American Indian
      mothers at each of five stages of behavior change. Participants were recruited
      from a Women, Infants and Children program located on the Pine Ridge Indian
      Reservation in South Dakota. Instruments included the 7-day Activity Recall,
      Stages of Exercise Adoption tool, Pros and Cons to Exercise tool, Self-efficacy
      for Exercise scale, and the Processes of Exercise Adoption tool. FINDINGS:
      Significant relationships were found between stage of change and energy
      expenditure indices (r = 0.69-0.74, p < .01), pros (r = 0.62, p < .01), cons (r =
      -0.58, p < .05), decisional balance (r = 0.59, p < .01), and self-efficacy (r =
      0.60, p < .01). Pros and cons were different from a prior study of mothers
      attending the Women, Infants and Children program. CONCLUSIONS: The
      Transtheoretical Model is relevant to American Indian mothers and should be
      tested in future physical activity interventions.

PMID- 16465110
TI  - The Scandinavian total ankle replacement (STAR).
AB  - Ankle joint arthritis is a condition that affects many people. Initial
      conservative treatment includes nonsteroidal antiinflammatory drugs, soft
      bracing, and ankle foot orthosis. When conservative management fails, surgical
      intervention is often considered. Previously an ankle joint fusion has been
      considered the "gold standard" to treat disabling ankle joint arthritis because
      early total ankle joint replacements had unacceptably high complication rates.
      However, early and midterm data have demonstrated that the Scandinavian Total
      Ankle Replacement (STAR) or Agility Total Ankle may be a reasonable alternative
      to an ankle joint fusion.

PMID- 16465113
TI  - Do your patients understand?: How to write effective healthcare information.

PMID- 16465115
TI  - Unraveling the mystery of HIV medications.
AB  - Today, millions of people around the globe are infected with human
      immunodeficiency virus (HIV). This retrovirus attacks and renders ineffective the
      human immune system and leads to acquired immunodeficiency syndrome (AIDS), which
      leaves those with AIDS open to a variety of fatal infections. HIV knows no
      racial, gender, or age distinctions, and there is, as yet, no cure for HIV.
      However, after 25 years of research, there are three classes of medication that
      in various combinations may significantly slow the progress of HIV, thus
      improving and prolonging the life of infected individuals. Nurses in any practice
      arena will inevitably care for patients who are infected with HIV. With an
      understanding of HIV and the therapeutic benefits of antiretroviral medications,
      informed nurses have the opportunity and responsibility to educate infected
      persons in the appropriate use of antiretroviral drugs and the importance of
      preventing transmission of HIV to uninfected persons.

PMID- 16465117
TI  - [Unilateral ocular ischemic syndrome in a diabetic patient].
AB  - PURPOSE: To report a case of ocular ischemic syndrome in a diabetic patient.
      METHODS: The patient's main complaint was an insidious unilateral decrease in
      visual acuity of the right eye. This diabetic 60-year-old patient presented
      numerous vascular risk factors. RESULTS: Diagnosis was suspected from the fundus
      examination and was confirmed on ultrasonic carotid imaging combined with MR
      angiography showing a significant internal carotid artery stenosis. CONCLUSION:
      This case should remind clinicians to be cautious when dealing with any
      asymmetric ophthalmological exam. The diagnosis of ocular ischemic syndrome has
      to be suspected in case of unilateral retinal ischemia.

PMID- 16465116
TI  - [Inflammatory presentation of a cavernous dural fistula: diagnosis with color and
      pulse Doppler imaging].
AB  - We report a case of a cavernous dural fistula in a 54-year-old man the source of
      inflammatory ocular symptoms. Poorly adapted treatment with corticosteroids led
      to iatrogenic complications. We will attempt to show the advantage of color
      Doppler imaging for the diagnosis of this infrequent lesion. The only indication
      of digitalized angiography is for endovascular treatment.

PMID- 16465118
TI  - [In vivo assessment of corneal epithelial toxicity of timolol with benzalkonium
      chloride using very-high-frequency ultrasound imaging].
AB  - PURPOSE: To assess in vivo the corneal epithelial damage caused by a topical
      toxic medication using a 60-MHz ultrasound device. MATERIAL: and methods: A
      solution of timolol with 0.01% benzalkonium chloride (BAC) was applied twice a
      day in the test eyes of ten rabbits, and a BAC-free solution of timolol in the
      control eyes, for 56 days. We used a 60-MHz ultrasound device to evaluate the
      epithelial damage in BAC-exposed eyes, compared to control eyes. The clinical and
      ultrasound examinations were performed every week, and the histological analysis
      at the end of the experiment. RESULTS: The clinical findings were conjunctival
      redness, corneal staining and instability of the tear film. In vivo VHF
      ultrasound revealed a thinning of the epithelium of test eyes (from 40.9+/-1,6
      microm at D0 to 31.8+/-3.4 microm at D56; p=0.0006 for D0 vs D56), while the
      epithelium of control eyes remained unchanged. Ultrasound epithelial thickness
      was correlated with corneal staining (at D34 and D56; p=0.0025 and 0.0377,
      respectively) and histological epithelial pachymetry (p=0.0176 for control and
      0.0505 for tested epithelium). Moreover, we report qualitative VHF ultrasound
      imaging of early epithelial damage. CONCLUSION: This new device could be very
      useful in ocular toxicity evaluation as a reproducible and reliable tool for
      multicentric clinical research.

PMID- 16465119
TI  - [Perforating ocular injuries in children: a retrospective study of 57 cases].
AB  - PURPOSE: The purpose of this study was to investigate the current causes and
      outcomes of open eye injuries in children. PATIENTS AND METHODS: We reviewed the
      hospital records of 57 patients under 14 years of age who were treated for open
      globe injuries at Edouard Herriot Hospital, Lyon, France, between January 1999
      and December 2003. RESULTS: This review includes 57 patients: 41 males and 16
      females. The mean age at admission was 6.8 +/- 3.5 years. The injury involved the
      right eye in 27 cases and the left eye in 30 cases. Sharp or pointed objects
      accounted for the majority of injuries. The most common location for a
      perforating ocular injury to occur was at home. Wounds involved the cornea in 41
      cases. There was iris hernia in 21 cases, hyphema in 15 cases, vitreous prolapse
      in 14 cases, lens damage in 12 cases, and shallow anterior chamber in 11 cases.
      The most frequent complication was traumatic cataract. Secondary lens removal was
      performed in 15 cases. Visual acuity was 0.5 or better in 27 of the 57 eyes, with
      a mean follow-up period of 12 months. CONCLUSIONS: Perforating ocular injuries
      are a frequent cause of unilateral visual loss. The highest proportion of
      injuries occurred at home and sharp objects were the most frequent causative
      agents. More adequate adult supervision and educational measures are necessary in
      order to reduce the prevalence of these accidents.

PMID- 16465120
TI  - [Cerebral visual impairment in brain-damaged children - four case studies].
AB  - Cerebral visual impairment is one of the main causes of childhood visual
      impairment in developed countries. These disorders are often linked with pre- or
      perinatal hypoxic brain injuries. The patterns of brain injuries depend on the
      severity and duration of hypoxia and the child's age. In premature children,
      periventricular leukomalacia affects the optic radiations and the subcortical
      visual brain. In full-term newborn babies, chronic hypoxia leads to the damage of
      the visual cortex and acute hypoxia damages the basal ganglia. They recover from
      cortical blindness in variable ways. Visual dysfunction is characterized by
      fixation troubles, subnormal acuity (crowding), difficulty with perceiving visual
      fields, movements, depth, cognitive defects (agnosia of images, objects or faces,
      visuospatial disorders), ocular motility disorders (tonic gaze deviation,
      strabismus, nystagmus). Accompanying these cerebral injuries, there are
      accommodation defects and optic disk abnormalities that vary according to the
      gestational age at the time of hypoxia.

PMID- 16465121
TI  - [Effect of nitrites and nitrates on bovine retina in vitro].
AB  - BACKGROUND/AIM: Uveitis is an endocular inflammation that forms one of the most
      serious manifestations of Behcet disease. Nitric oxide (NO) is a molecule that
      expresses important immunoinflammatory properties and is produced by NO synthases
      (NOS). In previous studies, we showed an elevated production of endogenous NO
      during Behcet's and idiopathic uveitis. These results led us to investigate the
      effect of nitrites (NO2-) and nitrates (NO3-) (physiologically stable metabolites
      of NO) on fragments of bovine retina in order to determine the role of nitric
      oxide (NO) in the genesis of retinal lesions during uveitis. MATERIAL AND
      METHODS: Retinas were removed from freshly enucleated bovine eyes and cultured in
      DMEM, 10% CFS in presence of nitrites (NaNO2) or nitrates (NaNO3) at different
      concentrations. The cultures were processed at 37 degrees C, 5% CO2 in a
      humidified chamber. Cultured retinas were observed by inverse microscopy and then
      fixed in formaldehyde. Histological studies were conducted after H & E staining.
      RESULTS: Cultured retina showed alterations when exposed to concentrations of
      nitrites and nitrates higher than 200 microM and 250 microM, respectively. These
      alterations were dose-dependent and affected the cellular and tissular
      structures. Morphological and histological studies suggested that the toxic
      effect is apoptotic and/or necrotic for both effectors. CONCLUSION: Our
      investigations showed that nitrites and nitrates, two physiologically stable
      metabolites of NO, have a deleterious effect on cultured retina. NO, produced in
      inflammatory processes during uveitis may be implicated in the genesis of the
      retinal lesions observed during the exacerbation phase of the disease.

PMID- 16465122
TI  - [Surgical results in childhood primary comitant large-angle exotropia].
AB  - INTRODUCTION: The purpose of this study was to evaluate the surgical results in
      childhood primary comitant large-angle exotropia (>30Delta) after a single
      operation and to analyze the factors that could influence these results. PATIENTS
      AND METHODS: We carried out a retrospective study in all children presenting with
      comitant primitive exotropia at an angle greater than 30Delta, who were operated
      on in our department from January 1996 to December 2000 by various surgeons. One
      hundred thirty-eight (138) cases were reviewed. The children with a substantial A
      or V phenomenon, retraction syndromes, nystagmus, those presenting with a
      neurological disease and those who had had previous eye surgery were excluded.
      The postoperative results were classified in three categories: residual exotropia
      over 10Delta, good postoperative result (esotropia<10Delta, orthotropia or
      exotropia<10Delta), and consecutive esotropia over 10Delta. RESULTS: Ninety-seven
      children fulfilled the study criteria. Forty (41.2%) were boys and 57 (58.8%)
      girls. The average age at the time of surgery was 6.5 years (SD 3.1). Sixty-eight
      of 97 (70.1%) had intermittent exotropia. Twenty-six children (26.8%) underwent a
      bilateral recession of the lateral rectus, 67 (69.1%) a unilateral operation,
      recession of a lateral rectus/resection of a medial rectus, and four (4.1%) an
      operation on three horizontal muscles. Sixty-nine percent of the children
      operated on had a good postoperative result, according to criteria defined in our
      study, 1 year after surgery. DISCUSSION/CONCLUSION: Childhood primary comitant
      large-angle exotropia can be corrected with a single surgical procedure,
      unilateral or bilateral, with a success rate which, in our study, reached 69%.

PMID- 16465123
TI  - [Visual dysfunction and arterial occlusion: is there an association with factor V
      Leiden mutation? Four case reports].
AB  - INTRODUCTION: The Leiden mutation of the factor V gene and the subsequent
      resistance of factor V to inactivation by activated protein C are associated with
      a procoagulant state, especially in the venous bed. However, its association with
      arterial thrombotic disease remains unclear. OBSERVATIONS: We report four
      patients with visual field defects secondary to arterial occlusions and in whom
      we found a factor V Leiden mutation. These patients, three females and one male,
      aged 32-58 years, presented with various visual field defects: bilateral arciform
      scotomas due to multiple infarcts of the nerve fiber layer (one case), superior
      defect due to anterior ischemic optic neuropathy (one case), homonymous
      hemianopia due to stroke (two cases). An abnormal resistance to activated protein
      C and a heterozygous state for factor V Leiden mutation were found in all four
      cases. The two patients who suffered from a stroke also showed elevated
      antiphospholipid antibodies (one case) and a patent foramen ovale (one case).
      COMMENTS AND CONCLUSION: Conflicting reports on the effective role of factor V
      Leiden mutation in arterial thrombotic events are present in the literature. We
      report four cases of arterial occlusion in whom a thrombophilic predisposition
      was present with a heterozygous state for factor V Leiden mutation. In two cases,
      no other risk factor was found. We hypothesize that factor V Leiden mutation,
      even in a heterozygous state, might predispose to arterial occlusion in some
      patients.

PMID- 16465124
TI  - [Actinomycotic lachrymal canaliculitis: a case report].
AB  - The authors report a case of unilateral chronic epiphora resistant to prolonged
      topical antibiotic treatment in a 62-year-old woman. Culture yielded some
      colonies of Actinomyces species. A dacryocystorhinostomy was found to be
      ineffective. Canaliculotomy with removal of cast resolved the chronic
      canaliculitis. Histological examination confirmed the diagnosis of solid cast of
      Actinomyces.

PMID- 16465125
TI  - [Multiple embolizations of the branches of the ophthalmic artery: an unknown
      serious complication of facial surgeries].
AB  - We present a patient with ocular ischemia following autologous refined fat
      injection (lipostructure) into the glabellar area to treat wrinkles. We think
      this visual loss is directly a consequence of the surgery, by retrograde
      arteriolar microembolus into the ophthalmic artery via peripheral anastomoses
      with the arteries of the face. These complications are on the rise because of the
      esthetic facial injections of viscous materials. We explain the pathophysiology
      and present a review of the litterature.

PMID- 16465126
TI  - [Multiple bilateral retinomas. A case study].
AB  - The case of an asymptomatic 29-year-old male patient with bilateral multiple
      retinomas is described. Initially misdiagnosed as unilateral pathological myopia
      10 years earlier, his ocular tumors were recognized only when examined after
      detection of bilateral retinoblastoma in his daughter. There was a large gray
      translucent mass and extensive chorioretinal atrophy in the right fundus and four
      small discrete tumors in the nasal periphery of the left fundus. There was no
      progression over 4 years of follow-up. Timely and correct diagnosis of retinoma
      is essential for appropriate genetic counseling, which would minimize the risk of
      retinoblastoma in future generations.

PMID- 16465127
TI  - [Glaucoma - structural imagery: HRT, GDX, OCT].
AB  - Confocal scanning laser tomography (HRT), scanning laser polarimetry (GDx VCC),
      and optical coherence tomography provide quantitative data of the retinal fiber
      layer and optic nerve head. They have become good complementary evaluation tools
      for glaucomatous optic neuropathy and their results should be analyzed with
      clinical data. Good knowledge of the parameters they analyze and their
      limitations are indispensable. To monitor progression of structural involvement,
      the analysis programs used need to be validated with prospective clinical
      studies.

PMID- 16465128
TI  - [Bacterial adhesion to intraocular lenses and endophthalmitis prevention: review
      of the literature].
AB  - Bacterial adhesion to intraocular lenses (IOLs) during their implantation is a
      major etiological factor of postoperative endophthalmitis. Polypropylene was the
      first biomaterial that allowed this relation of cause and effect between
      bacterial adhesion and endophthalmitis to be proven. Adhesion to IOLs has been
      investigated in several in vitro studies, with contradictory results reported,
      due to variations in experimental conditions: the incubation times and the
      methods all varied. Adhesion is affected by the type of IOL, the bacterial
      strains, and the surrounding medium. Since this medium is very difficult to model
      because of its complexity, in vivo studies seemed essential. We have recently
      determined in vivo progression in the amount of adhering Staphylococcus
      epidermidis to five types of IOLs. There have been few epidemiological studies
      published to determine the relationship between endophthalmitis and the IOL type.
      However, the perfect biomaterial that could prevent postoperative endophthalmitis
      does not yet exist. Globally, hydrophilic materials and hydrophobic acrylic seem
      to be less sticky than silicone or PMMA, but this remains to be proven
      clinically.

PMID- 16465129
TI  - [How to perform intravitreal injections].
AB  - Drugs to treat retinal diseases are often injected intravitreally. This procedure
      can cause severe complications. We present ways to minimize the risk for
      complications. Rigorous preoperative antisepsis with povidone iodine, a sterile
      environment (using gloves and a mask for the injector, a lid speculum, and a
      drape on the eye to be injected), and immediate follow-up after injection are key
      issues of the injection technique.

PMID- 16465130
TI  - [Neurophysiological basis and clinical tests for assessment of X-linked color
      vision deficiencies in school children].
AB  - Vision screening of school children at 5-6 years of age must include color vision
      screening. X-linked dyschromatopsia is the most frequent disorder affecting 8% of
      boys and 0.4% of girls. This paper presents the physiology of these deficiencies
      caused by an alteration of the spectral absorption properties of one of the cone
      pigments (protanomalous or deuteranomalous trichromats) or the absence of one of
      the pigments (protanopia or deuteranopia), the most frequent. Absence of two of
      the pigments (blue cone monochromacy) is very rare and differs from
      achromatopsia. The physiological basis of the main tests for easy clinical
      screening are presented. Testing methods designed for children are reviewed. The
      Ishihara test is the most widely used screening test specific for congenital
      color defects. If the plates are correctly read, the child has normal color
      vision. If not, arrangement tests such as Panel D 15 and desaturated Panel D 15
      tests can be used to diagnose the type of the defect (protan or deutan) and grade
      the degree of color deficiency according to a strategy adapted to children.
      Examples of results are presented for each axis along which caps are confused,
      providing a quick and easy preliminary diagnosis. Early detection of color vision
      malfunction in children allows parents and teachers to make necessary adjustments
      to the teaching methods for appropriate learning.

PMID- 16465132
TI  - [Ocular trauma caused by a beebee gun].

PMID- 16465131
TI  - [Risk factors for early congenital esotropia].
AB  - To elucidate risk factors for congenital esotropia, this review reports on
      articles written on congenital esotropia during the past few years. The authors
      distinguish the significant risk factors of esotropia such as heredity,
      prematurity, perinatal difficulties, and minor risk factors such as ametropia,
      primary monofixation, and environmental factors.

PMID- 16465134
TI  - [Statistical study of dermatomycosis - observations in Sendai National Hospital
      over a 30 year period].
AB  - A statistical 30-year study of dermatomycosis in Sendai National Hospital (1968
      1997) revealed many changes in the prevalent diseases: Tinea pedis and tinea
      unguium constantly increased during this period, and the ratio of the former
      associated with nail infection finally reached 30% of all tinea pedis patients.
      On the contrary, tinea corporis and cruris showed a remarkable decreasing
      tendency. Patient age distribution of each disease also showed distinctive
      changes, generally increasing in the older generation and decreasing in the
      younger. The number of patients with tinea pedis and unguium gradually increased
      among the middle and older generations, with the peak of the age-distribution
      curve shifting upward year after year. On the other hand, cases of tinea cruris
      among the younger generation were few in the latest years, and middle-age
      patients remained at a low number. In the first stage of this study the kinds of
      atiologic dermatophytes consisted of multiple species, but after middle period
      the isolation of Epidermaphyton floccosum decreased. Microsporum canis appeared
      first in 1976 but in the recent several years has completely disappeared. In the
      last few years of the period studied Trichophyton rubrum and Trichophyton
      mentagrophytes were the only isolates found from among all types of
      dermatophytoses. Infantile candidiasis remarkably increased in 1970-1975 but
      thereafter decreased rapidlly. Candidial intertrigo also increased in the same
      period but did not decrease as much thereafter and continued at the same
      intermediate level. The number of other types of candidiases were not greatly
      changed throughout the 30-year period. Malassezia infection also showed no
      remarkable changes, and only 20 cases of sporothrichosis were found. One case of
      the deep seated form of cutaneous aspergillosis was found, and this was also true
      of chromomycosis caused by Fonceaea pedrosoi.

PMID- 16465135
TI  - [Comparative study between culture and PCR-RFLP analysis on identification of the
      causative agent of Tinea Unguium].
AB  - BACKGROUND: To identify the pathogenic fungi of dermatophytosis, restriction
      fragment length polymorphism (RFLP) analysis of PCR amplified ribosomal DNA
      including internal transcribed spacers (ITS) has been established in Japan. Our
      purpose was to evaluate the usability of PCR-RFLP analysis to identify the
      causative agent of tinea unguium directly from a nail sample. METHOD: Samples of
      tinea unguium from 100 nails were collected and cultured on Sabouraud's glucose
      agar and observed for 2 months. DNA was extracted from these samples, and the PCR
      product was digested with restriction enzymes Mva I and Hinf I. Weight of the
      samples was determined. RESULT: Sensitivity of PCR-RFLP analysis (73%) was higher
      than that of culture (20%) showing that PCR is more advantageous for
      identification of the causative agent of tinea unguium. Sensitivity of PCR-RFLP
      did not depend on weight of the nail sample.

PMID- 16465136
TI  - [Epidemiology of visceral mycoses in patients with leukemia and MDS - Analysis of
      the data in annual of pathological autopsy cases in Japan in 1989, 1993, 1997 and
      2001].
AB  - To study the changes of visceral mycoses in autopsy cases, data on visceral
      mycosis cases with leukemia and myelodysplastic syndrome (MDS) reported in the
      Annual of the Pathological Autopsy Cases in Japan in 1989, 1993, 1997 and 2001
      were analyzed. The frequency rate of visceral mycoses with leukemia and MDS was
      27.9% (435/1,557) in 1989, 23.0% (319/1,388) in 1993, 22.3% (246/1,105) in 1997
      and 25.1% (260/ 1,037) in 2001, which was clearly higher than the rate of cases
      without leukemia and MDS: 3.4%, 2.7%, 3.5% and 3.7%, respectively. Furthermore,
      in comparing the rate of mycoses in recipients of stem cell transplantation with
      that of non-recipients, that of recipients was about 10% higher. The predominant
      causative agents were Candida and Aspergillus, at approximately the same rate
      (Candida 33.6%, Aspergillus 33.3%) as in 1989. However, Aspergillus increased
      conspicuously in 1993 (Candida 22.3% Aspergillus 44.5%), and continued to
      increase (Candida 22.8%, Aspergillus 50.8% in 1997; Candida 16.9%, Aspergillus
      54.2% in 2001). In aspergillosis and zygomycosis, the lung and bronchi comprised
      the most commonly infected organs: 74.7% and 75.6% of the total cases,
      respectively. Among a total of 1,260 cases with mycotic infections in the four
      years studied, acute lymphatic leukemia and acute myeloid leukemia were the major
      diseases (35.5% and 33.5%, respectively) followed by MDS (29.0%). Given these
      facts, we emphasize that a greater interest in mycoses should be taken by
      clinicians, and immunocompromised patients should be protected from opportunistic
      invasive fungal infections, especially aspergillosis.

PMID- 16465137
TI  - [Combined effect of micafangin and itraconazole on severe aspergillosis of the
      bilateral pleural cavities in a patient with Wegener's granulomatosis].
AB  - Visceral fungal infections are difficult to manage in patients with collagen
      diseases and immunocompromised hosts. In particular aspergillosis can be a life
      threatening complication in these patients. Here we report that combined use of
      two antifungal agents (micafangin and itraconazole) was effective against severe
      aspergillosis of the bilateral pleural cavities in a 48-year old male patient
      diagnosed with Wegener's granulomatosis. Immunosuppressive therapy with
      corticosteroids and cyclophosphamides improved his nasal and pulmonary symptoms,
      but inflammation of the bilateral pleural cavities caused bronchial fistulas.
      Aspergillus fumigatus then infected the bilateral pulmonary cavities through
      these fistulas. This patient was treated with combined therapy of ITCZ and MCFG
      was given to this patient because of the risk of renal dysfunction associated
      with AMPH-B. After 5 weeks of treatment his clinical findings had improved and
      the fungus was suppressed.

PMID- 16465138
TI  - In it for the long haul.

PMID- 16465139
TI  - China offers alternative gateway for experimental drugs.

PMID- 16465140
TI  - Amgen becomes a stronger cancer player.

PMID- 16465141
TI  - Industry warily eyes new Medicare drug plan.

PMID- 16465142
TI  - Nanomedicine lacks recognition in Europe.

PMID- 16465144
TI  - Profile: Einer Elhauge.

PMID- 16465145
TI  - 2005: biotech partners up.

PMID- 16465146
TI  - The second wave in kinase cancer drugs.

PMID- 16465147
TI  - Depicting signaling cascades.

PMID- 16465149
TI  - Sequencing thoroughbreds.

PMID- 16465150
TI  - A DNA flu vaccine in practice.

PMID- 16465151
TI  - South Korean policy failure and the Hwang debacle.

PMID- 16465152
TI  - When your stock takes a nosedive.

PMID- 16465153
TI  - A turbulent year at the agency.

PMID- 16465154
TI  - The importance of getting inventorship right.

PMID- 16465155
TI  - Recent patent applications in angiogenesis research.

PMID- 16465156
TI  - The next chapter in reverse vaccinology.

PMID- 16465157
TI  - AAV does the shuffle.

PMID- 16465158
TI  - The medium is the message.

PMID- 16465159
TI  - Plants tackle explosive contamination.

PMID- 16465160
TI  - Designer combination therapy for cancer.

PMID- 16465162
TI  - Statistical practice in high-throughput screening data analysis.
AB  - High-throughput screening is an early critical step in drug discovery. Its aim is
      to screen a large number of diverse chemical compounds to identify candidate
      'hits' rapidly and accurately. Few statistical tools are currently available,
      however, to detect quality hits with a high degree of confidence. We examine
      statistical aspects of data preprocessing and hit identification for primary
      screens. We focus on concerns related to positional effects of wells within
      plates, choice of hit threshold and the importance of minimizing false-positive
      and false-negative rates. We argue that replicate measurements are needed to
      verify assumptions of current methods and to suggest data analysis strategies
      when assumptions are not met. The integration of replicates with robust
      statistical methods in primary screens will facilitate the discovery of reliable
      hits, ultimately improving the sensitivity and specificity of the screening
      process.

PMID- 16465163
TI  - Screening for peptide drugs from the natural repertoire of biodiverse protein
      folds.
AB  - Although monoclonal antibody (mAb) drugs targeting protein interactions exist,
      these therapeutics cannot access intracellular proteins involved in disease
      complexes. Moreover, mAbs are more difficult to deliver and are frequently
      associated with a prohibitive 'royalty stack.' Outlined here is an alternative
      approach based on libraries of natural, highly structured peptides that offers
      new opportunities for identifying effective, specific inhibitors of protein
      protein interactions. Libraries of such peptides (referred to hereafter as
      phylomers) comprise both random and structured peptides encoded by natural genes
      of diverse bacterial genomes. Because the number of protein subdomain structures
      found in nature is limited, diverse libraries containing millions of phylomers
      constitute virtually all of the available classes of protein fold structures,
      providing a rich source of peptides that interact specifically and with high
      affinity to human proteins. This approach may help not only in understanding the
      implications of each interaction identified within the interactome but also in
      the development of effective drugs targeted to particular protein functions.
      Although phylomers are active in animal models, the challenge remains to
      demonstrate efficacy and safety in a clinical setting.

PMID- 16465169
TI  - Chinese biotech: the need for innovation and higher standards.

PMID- 16465171
TI  - MRI directed multidisciplinary team preoperative treatment strategy: the way to
      eliminate positive circumferential margins?
AB  - Histopathological audit of positive circumferential resection margins (CRMs) can
      be used as a surrogate measure of the success of rectal cancer treatment. We
      audited CRM involvement in rectal cancer patients and the impact of the
      multidisciplinary team (MDT) on implementing a magnetic resonance imaging (MRI)
      based preoperative treatment strategy. Data were collected on all newly diagnosed
      rectal cancer patients treated in our network between January 1999 and December
      2002. Data were analysed for MRI prediction and histopathological assessment of
      CRM together with the MDT meeting treatment decisions. The CRM+ve rate of those
      discussed at MDT vs those not discussed were compared. We re-audited the CRM+ve
      rates 1 year after introducing a policy of mandatory preoperative MRI-based MDT
      discussion. Of the 298 patients diagnosed with rectal cancer, 39 (13%) were
      deemed palliative, 178 underwent surgery alone and 81 underwent neoadjuvant
      therapy. Of these, 62 out of 178 patients underwent surgery alone without MRI
      based MDT discussion resulting in positive CRM in 16 cases (26%) as compared to 1
      out of 116 (1%) in those patients with MDT discussion of MRI. Overall CRM+ve rate
      in all nonpalliative patients with or without MDT discussion was 12.5% (32 out of
      256), significantly lower than the <20% rate (P<0.001) quoted in national
      guidelines. Re-audit in 98 consecutive patients following a change of policy
      produced a lower CRM+ve rate of 3% (1 out of 37) for all surgery alone patients
      and an overall CRM+ve rate of 7% (5 out of 70). In conclusion, MDT discussion of
      MRI and implementation of a preoperative treatment strategy results in
      significantly reduced positive CRM in rectal cancer patients.

PMID- 16465172
TI  - Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in
      rectal cancer: should we be more cautious?
AB  - Neoadjuvant chemotherapy (NACT) is a term originally used to describe the
      administration of chemotherapy preoperatively before surgery. The original
      rationale for administering NACT or so-called induction chemotherapy to shrink or
      downstage a locally advanced tumour, and thereby facilitate more effective local
      treatment with surgery or radiotherapy, has been extended with the introduction
      of more effective combinations of chemotherapy to include reducing the risks of
      metastatic disease. It seems logical that survival could be lengthened, or organ
      preservation rates increased in resectable tumours by NACT. In rectal cancer NACT
      is being increasingly used in locally advanced and nonmetastatic unresectable
      tumours. Randomised studies in advanced colorectal cancer show high response
      rates to combination cytotoxic therapy. This evidence of efficacy coupled with
      the introduction of novel molecular targeted therapies (such as Bevacizumab and
      Cetuximab), and long waiting times for radiotherapy have rekindled an interest in
      delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm
      is currently waning in other sites such as head and neck and nasopharynx cancer
      where traditionally NACT has been used. So, is NACT in rectal cancer a real
      advance or just history repeating itself? In this review, we aimed to explore the
      advantages and disadvantages of the separate approaches of neoadjuvant,
      concurrent and consolidation chemotherapy in locally advanced rectal cancer,
      drawing on theoretical principles, preclinical studies and clinical experience
      both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may
      improve outcome in terms of disease-free or overall survival in selected groups
      in some disease sites, but this strategy has not been shown to be associated with
      better outcomes than postoperative adjuvant chemotherapy. In particular, there is
      insufficient data in rectal cancer. The evidence for benefit is strongest when
      NACT is administered before surgical resection. In contrast, the data in favour
      of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the
      suggestion that response to induction chemotherapy can predict response to
      subsequent radiotherapy. The observation that spectacular responses to
      chemotherapy before radical radiotherapy did not result in improved survival, was
      noted 25 years ago. However, multiple trials in head and neck cancer,
      nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and
      cervical cancer do not support the routine use of NACT either as an alternative,
      or as additional benefit to CRT. The addition of NACT does not appear to enhance
      local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy
      before CRT or radiation should be used with caution, and only in the context of
      clinical trials. The evidence base suggests that concurrent CRT with early
      positioning of radiotherapy appears the best option for patients with locally
      advanced rectal cancer and in all disease sites where radiation is the primary
      local therapy.

PMID- 16465173
TI  - The effectiveness of treatment for depression/depressive symptoms in adults with
      cancer: a systematic review.
AB  - Depression is common in cancer patients, and this often remains undetected and
      untreated. Depression has been associated with poorer quality of life, in
      addition to increased impairment of immune response and poorer survival in cancer
      patients. Previous systematic reviews and meta-analyses of the efficacy of
      interventions for cancer patients with depression have failed to distinguish
      between caseness for depression and depressive symptoms. The findings from this
      systematic review show that there is limited trial data on the efficacy of
      prescribed antidepressants in reducing the incidence of major depression and
      depressive symptoms in cancer patients. Contrary to previous reviews that failed
      to distinguish between depressive symptoms and depression, this review found very
      little data from clinical trials (without the possibility of confounding factors)
      to demonstrate that psychotherapeutic interventions are effective in reducing
      depression in cancer patients. A number of small-scale, single-centre trials
      indicated that psychotherapeutic interventions (especially cognitive behavioural
      therapy) can have effects on depressive symptoms in cancer patients. However,
      given the methodological limitations of studies to date, lack of evidence should
      not be interpreted as implying lack of efficacy. In conclusion, there is a need
      for adequately powered studies of pharmacological and psychotherapeutic studies,
      which are targeted at cancer patients with a diagnosis of depression and include
      monitoring of the use of other pharmacological/psychotherapeutic and
      complementary and alternative medicine interventions.

PMID- 16465175
TI  - The physiology and pharmacology of the lower urinary tract. Proceedings of the
      3rd BJP Symposium, December 2005.

PMID- 16465174
TI  - Neoadjuvant chemotherapy in breast cancer: early response prediction with
      quantitative MR imaging and spectroscopy.
AB  - A prospective study was undertaken in women undergoing neoadjuvant chemotherapy
      for locally advanced breast cancer in order to determine the ability of
      quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to
      predict ultimate tumour response (percentage decrease in volume) or to detect
      early response. Magnetic resonance imaging and MRS were carried out before
      treatment and after the second of six treatment cycles. Pharmacokinetic
      parameters were derived from T1-weighted dynamic contrast-enhanced MRI, water
      apparent diffusion coefficient (ADC) was measured, and tissue water:fat peak area
      ratios and water T2 were measured using unsuppressed one-dimensional proton
      spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and
      ADC did not detect early response; however, early changes in water:fat ratios and
      water T2 (after cycle two) demonstrated substantial prognostic efficacy. Larger
      decreases in water T2 accurately predicted final volume response in 69% of cases
      (11/16) while maintaining 100% specificity and positive predictive value.
      Small/absent decreases in water:fat ratios accurately predicted final volume non
      response in 50% of cases (3/6) while maintaining 100% sensitivity and negative
      predictive value. This level of accuracy might permit clinical application where
      early, accurate prediction of non-response would permit an early change to second
      line treatment, thus sparing patients unnecessary toxicity, psychological
      morbidity and delay of initiation of effective treatment.

PMID- 16465176
TI  - The role of central 5-hydroxytryptamine (5-HT, serotonin) receptors in the
      control of micturition.
AB  - At present the most investigated 5-HT receptor that has been shown to play a role
      in the control of micturition is the 5-HT(1A) receptor followed by 5-HT(7), 5
      HT(2) and 5-HT(3) receptors. Most experiments focus on the control these
      receptors have on the parasympathetic outflow to the bladder and the somatic
      outflow to the external urethral sphincter (EUS) in the rat. Furthermore, 5
      HT(1A) and 5-HT(7) receptors have been identified as having an excitatory
      physiological role in the control of bladder function. 5-HT(1A) receptors act, at
      least in the rat, at both a spinal (probably a heteroreceptor) and supraspinal
      (probably an autoreceptor) level, while 5-HT(7) receptors only act at a
      supraspinal level. Additionally, in the rat, 5-HT administered at a spinal or
      supraspinal site has an excitatory action, although earlier experiments have
      shown that activating 5-HT-containing brain areas causes inhibition of the
      bladder. Recent experiments have also indicated that blockade of the 5-HT(1A)
      receptor pathway shows rapid tolerance. However, no data exist for the
      development of tolerance for the 5-HT(7) receptor pathway. Neither receptor seems
      to play a role in the control of the urethra. Regarding 5-HT(2) receptors,
      activation of this receptor subtype inhibits micturition, and this inhibitory
      action may occur at a spinal, supraspinal or both levels. Although no
      physiological role for 5-HT(2C) receptors can yet be identified, 5-HT(2C)
      receptors have been implicated in the proposed supraspinal tonically active 5
      HT(1A) autoreceptor (negative feedback) pathway. This proposition reconciles the
      data that central 5-HT-containing pathways are inhibitory to micturition, while 5
      HT(1A) receptors, although inhibitory to adenylyl cyclase, have an excitatory
      function. This is because activation of 5-HT(1A) autoreceptors reduces the
      release of 5-HT thus reducing the activation of the 5-HT(2C) receptors, which are
      inhibitory in the control of micturition (disinhibition). Furthermore, 5-HT(2A)
      receptors in the rat and 5-HT(2C) receptors in the guinea pig cause activation of
      the EUS. In this respect, 5-ht(5A) receptors have also been identified in Onuf's
      nucleus, the site of somatic motoneurones controlling this sphincter. In the cat
      there is very little evidence to indicate that 5-HT receptors are involved in
      micturition except under pathological conditions in which activation of 5-HT(1A)
      receptors causes inhibition of micturition. Interestingly, under such conditions
      5-HT(1A) receptors cause excitation of the EUS. Nevertheless, spinal 5HT(3)
      receptors have been implicated in the physiological control of micturition in the
      cat, but not yet in the rat. Overall, the data support the view that 5-HT
      receptors are important in the control of micturition. However, many more studies
      are required to fully understand these roles and why there are such species
      differences.

PMID- 16465177
TI  - Purinoceptors as therapeutic targets for lower urinary tract dysfunction.
AB  - Lower urinary tract symptoms (LUTS) are present in many common urological
      syndromes. However, their current suboptimal management by muscarinic and
      alpha(1)-adrenoceptor antagonists leaves a significant opportunity for the
      discovery and development of superior medicines. As potential targets for such
      therapeutics, purinoceptors have emerged over the last two decades from
      investigations that have established a prominent role for ATP in the regulation
      of urinary bladder function under normal and pathophysiological conditions. In
      particular, evidence suggests that ATP signaling via P2X(1) receptors
      participates in the efferent control of detrusor smooth muscle excitability, and
      that this function may be heightened in disease and aging. ATP also appears to be
      involved in bladder sensation, via activation of P2X(3) and P2X(2/3) receptors on
      sensory afferent neurons, both within the bladder itself and possibly at central
      synapses. Such findings are based on results from classical pharmacological and
      localization studies in non-human and human tissues, knockout mice, and studies
      using recently identified pharmacological antagonists--some of which possess
      attributes that offer the potential for optimization into candidate drug
      molecules. Based on recent advances in this field, it is clearly possible that
      the development of selective antagonists for these receptors will occur that
      could lead to therapies offering better relief of sensory and motor symptoms for
      patients, while minimizing the systemic side effects that limit current
      medicines.

PMID- 16465178
TI  - Integrated control of lower urinary tract--clinical perspective.
AB  - The neural mechanisms that determine social bladder control are reviewed, with a
      particular emphasis on the role played by sensation in the process. Much has been
      learnt about the neural control of the bladder from studying patients with
      neurological disease and those disorders that are known to disrupt bladder
      storage are described. Possible approaches to treatment of the resulting
      incontinence are reviewed and it is acknowledged that in the future, the optimal
      treatment for incontinence may be determined by its precise underlying
      pathophysiology in each instance, for example, suprapontine causes requiring
      different medication to spinal causes. Although the main emphasis of urological
      research and development so far has been the treatment of incontinence, effective
      therapy for other bladder disorders such an impaired emptying or bladder pain
      could have an important impact on the bladder symptoms of many patients.

PMID- 16465179
TI  - Growth factor signalling in prostatic growth: significance in tumour development
      and therapeutic targeting.
AB  - The intricate balance maintained between cell growth and proliferation factors
      and apoptosis-inducing factors is fundamental to the regulation of prostate
      growth. Disruptions in this homeostasis often trigger the loss of apoptosis and
      the over-expression of factors promoting cell survival and proliferation,
      inevitably leading to tumorigenesis and cancer. Deregulation of prostate growth
      during prostate cancer development and progression is characterized by apoptotic
      evasion, uncontrolled proliferation, and increased invasive potential. Thus, in
      advanced stages of disease progression, surviving prostate tumour cells acquire
      the ability to migrate and invade heterotopic tissues, with the bone and lymph
      nodes being the most common sites for human prostate cancer metastasis. The
      challenges in the implementation of effective therapeutic strategies for the
      treatment of advanced metastatic prostate cancer reflect the multidimensional
      nature and functional significance of antiapoptotic pathways in the emergence of
      therapeutic resistance of prostate tumours. In this chapter, we discuss the
      current understanding of the molecular mechanisms governing growth factor
      signalling pathways with often overlapping functions that contribute to loss of
      apoptosis control and activation of cell proliferation towards aggressive
      prostate tumorigenic growth and metastatic behaviour. While a full understanding
      of the prosurvival characteristics of these growth factor pathways is still
      evolving, the impact that growth factors such a epidermal growth factor and
      transforming growth factor-beta can be recognized by the vigorous attempts at
      therapeutic targeting of their key signalling steps.

PMID- 16465180
TI  - Late-stage clinical development in lower urogenital targets: sexual dysfunction.
AB  - In recent years, late-stage clinical drug development that primarily focuses on
      urogenital targets has centered around four areas of medical need (both unmet
      need and aiming to improve on existing therapies). These include male sexual
      dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology
      (neoplastic, pre-neoplastic, and non-neoplastic), and improvement in lower
      urinary tract symptoms. Despite the regulatory approval of compounds to treat
      erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments
      for overactive bladder, and stress urinary incontinence, there remains a
      deficiency in addressing a number of conditions that arise out of
      pathophysiological dysfunction resulting in lower urogenital tract sexual
      conditions. In terms of late-stage clinical development, significant progress has
      most recently been made in MSD development, especially in understanding further a
      common and complex sexual dysfunction--that of premature ejaculation. The search
      also continues for compounds that improve ED in terms of better efficacy and
      superior safety profile compared to the currently marketed phosphodiesterase-5
      inhibitors. Whilst there are no approved medications to treat the subtypes of
      FSD, there has been significant progress in attempting to better understand how
      to appropriately assess treatment benefit in clinical trial settings for this
      difficult to diagnose and treat condition. This review will focus on late-stage
      human clinical development pertaining to MSD and FSD.

PMID- 16465182
TI  - Integrative control of the lower urinary tract: preclinical perspective.
AB  - Storage and periodic expulsion of urine is regulated by a neural control system
      in the brain and spinal cord that coordinates the reciprocal activity of two
      functional units in the lower urinary tract (LUT): (a) a reservoir (the urinary
      bladder) and (b) an outlet (bladder neck, urethra and striated muscles of the
      urethral sphincter). Control of the bladder and urethral outlet is dependent on
      three sets of peripheral nerves: parasympathetic, sympathetic and somatic nerves
      that contain afferent as well as efferent pathways. Afferent neurons innervating
      the bladder have A-delta or C-fibre axons. Urine storage reflexes are organized
      in the spinal cord, whereas voiding reflexes are mediated by a spinobulbospinal
      pathway passing through a coordination centre (the pontine micturition centre)
      located in the brainstem. Storage and voiding reflexes are activated by
      mechanosensitive A-delta afferents that respond to bladder distension. Many
      neurotransmitters including acetylcholine, norepinephrine, dopamine, serotonin,
      excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide and
      neuropeptides are involved in the neural control of the LUT. Injuries or diseases
      of the nervous system as well as disorders of the peripheral organs can produce
      LUT dysfunctions including: (1) urinary frequency, urgency and incontinence or
      (2) inefficient voiding and urinary retention. Neurogenic detrusor overactivity
      is triggered by C-fibre bladder afferent axons, many of which terminate in the
      close proximity to the urothelium. The urothelial cells exhibit 'neuron-like'
      properties that allow them to respond to mechanical and chemical stimuli and to
      release transmitters that can modulate the activity of afferent nerves.

PMID- 16465181
TI  - Lower urinary tract disease: what are we trying to treat and in whom?
AB  - The diseases of the lower urinary tract are traditionally divided into
      abnormalities of storage and abnormalities of emptying. The targets for therapy
      were the organs most responsible for influencing storage and emptying. Modern
      understanding places the symptomatic status of the patient as the overriding
      criterion for treatment. It also accommodates a broader understanding of multiple
      and overlapping systems. Symptoms of voiding dysfunction have been clearly shown
      to be associated with symptoms of other genitourinary disease, for example,
      erectile dysfunction (ED). Treatment of voiding dysfunction has also been shown
      to have effects (adverse or beneficial) in these other domains. Thus, the
      symptoms of lower urinary tract disease (LUTD) that have to be considered now as
      targets relevant to these therapies include ED, ejaculatory dysfunction, sexual
      desire, sexual pain disorders and female sexual dysfunction. The anatomic, neural
      and endocrine systems that support these symptomatic functions and dysfunctions
      span the range from the urogenital smooth muscle to the hypothalamus, the bladder
      sensory output to the micturition centre and growth factors to androgens.
      Potentially important targets also include vascular and spinal structures, sex
      hormones and nitric oxide as well as the obvious genes, enzymes and receptors.
      The epidemiological studies prove the convergence of LUTD when viewed through the
      lens of the current patient-related outcomes and problem constructs. This
      convergence serves as a clear guidance to include wide ranging outcome
      instruments in all future studies with compounds being investigated for the
      treatment of LUTD. Out of these will come evidence of expected and unexpected
      collateral effects. The convergence should open the possibility to a different
      business model for developing therapeutic concepts. The blockbuster drug for a
      monolithic indication may be supplemented by agents with single or multiple
      pathway activity with smaller parallel targets. Using an approach based on
      patient reported outcomes to therapeutic targets not only widens the range of
      conditions, but also the patient types who can be considered as having LUTD.

PMID- 16465183
TI  - Molecular mechanisms of detrusor and corporal myocyte contraction: identifying
      targets for pharmacotherapy of bladder and erectile dysfunction.
AB  - The Post-Genomic age presents many new challenges and opportunities for the
      improved understanding, diagnosis and treatment of human disease. The long-term
      goal is to identify molecular correlates of disease processes, and use this
      information to develop novel and more effective therapeutics. A major hurdle in
      this regard is ensuring that the molecular targets of interest are indeed
      relevant to the physiology and/or pathophysiology of the processes being studied,
      and, moreover, to determine if they are specific to the tissue/organ being
      investigated. As a first step in this direction, we have reviewed the literature
      pertaining to bladder and erectile physiology/pharmacology and dysfunction and
      attempted to summarize some of the critical molecular mechanisms regulating
      detrusor and corporal myocyte tone. Because of the vast amount of published data,
      we have limited the scope of this review to consideration of the calcium
      mobilizing and calcium-sensitizing pathways in these cells. Despite obvious
      differences in phenotypic characteristics of the detrusor and corporal myocyte,
      there are some common molecular changes that may contribute to, for example, the
      increased myocyte contractility characteristic of bladder and erectile
      dysfunction (i.e. increased Rho kinase activity and decreased K(+) channel
      function). Of course, there are also some important distinctions in the pathways
      that modulate contractility in these two cell types (i.e. the contribution of
      ryanodine-sensitive calcium stores and the nitric oxide/cGMP pathways). This
      report highlights some of these similarities and distinctions in the hope that it
      will encourage scientific discourse and research activity in this area,
      eventually leading to an improved quality of life for those millions of
      individuals that are afflicted with bladder and erectile dysfunction.

PMID- 16465184
TI  - In vitro models: research in physiology and pharmacology of the lower urinary
      tract.
AB  - The physiology and pharmacology of the lower urinary tract has advanced based, in
      part, due to the in vitro assays that have facilitated this exploration. Such
      assays have led to the development of novel and selective molecules that have
      been used to characterize different receptor and enzyme systems in the larger
      context of in vivo pharmacology. These assays can be classified by sites of
      action of drugs into the following categories: receptors, effector enzymes and
      enzymes that terminate the responses. In this review, representative assays are
      presented based on our experience in male erectile dysfunction.

PMID- 16465186
TI  - Muscarinic receptors in the bladder: from basic research to therapeutics.
AB  - Muscarinic receptor antagonists (antimuscarinics) serve as the cornerstone in the
      pharmacological management of overactive bladder (OAB) by relieving the symptoms
      of urgency, frequency and incontinence. These drugs operate primarily by
      antagonizing post-junctional excitatory muscarinic receptors (M(2)/M(3)) in the
      detrusor. The combination of pharmacological and gene knockout studies has
      greatly advanced our understanding of the functional role of muscarinic receptors
      in the bladder. M(3) receptors produce direct smooth muscle contraction by a
      mechanism that relies on entry of extracellular calcium through L-type channels
      and activation of a rho kinase. M(2) receptors, which predominate in number,
      appear to facilitate M(3)-mediated contractions. M(2) receptors can also produce
      bladder contractions indirectly by reversing cAMP-dependent beta-adrenoceptor
      mediated relaxation, although the physiological role of beta-adrenoceptors in
      detrusor relaxation is controversial. Emerging evidence suggests that muscarinic
      receptors in the urothelium/suburothelium can modulate the release of certain
      factors, which in turn may affect bladder function at the efferent or afferent
      axis. Currently, oxybutynin, tolterodine, darifenacin, solifenacin and trospium
      are the five major antimuscarinics approved for the treatment of OAB. Comparative
      clinical studies have shown that oxybutynin and solifenacin may be marginally
      more effective than tolterodine, although the latter seems to be better
      tolerated. Pharmacokinetic-pharmacodynamic analyses using plasma concentrations
      of 'total drug' indicate that, at therapeutic doses, the clinical efficacy of
      darifenacin and solifenacin may be driven primarily by selective M(3) receptor
      occupation, whereas the pharmacodynamic effects of pan-selective molecules (such
      as tolterodine, trospium) may potentially involve multiple receptors, including
      M(2) and M(3). Furthermore, high M(3) receptor occupation is the likely
      explanation for the greater propensity of darifenacin and oxybutynin to cause dry
      mouth and/or constipation. Although the recently introduced drugs represent a
      significant improvement over older drugs, especially with respect to the
      convenience of dosing schedule, their overall efficacy and tolerability profile
      is still less than optimal and patient persistence with therapy is low. Recent
      advances in basic research have not yet offered a clear discovery path for
      improving the therapeutic index of antimuscarinic molecules. There is still an
      unmet need for an antimuscarinic medicine with superior clinical effectiveness
      that can translate into better persistence on therapy.

PMID- 16465189
TI  - Association of body mass index and height with risk of prostate cancer among
      middle-aged Japanese men.
AB  - In a population-based prospective study of 49 850 Japanese men, body mass index
      and height were not significantly associated with risk of prostate cancer (311
      cases), although small positive effects could not be ruled out in advanced cases
      (91 cases).

PMID- 16465185
TI  - Animal models in urological disease and sexual dysfunction.
AB  - There are several conditions associated with dysfunction of the lower urinary
      tract or which result in a reduction in the ability to engage in satisfactory
      sexual function and result in significant bother to sufferers, partners and/or
      carers. This review describes some of the animal models that may be used to
      discover safe and effective medicines with which to treat them. While alpha
      adrenoceptor antagonists and 5-alpha-reductase inhibitors deliver improvement in
      symptom relief in benign prostatic hyperplasia sufferers, the availability of
      efficacious and well-tolerated medicines to treat incontinence is less well
      served. Stress urinary incontinence (SUI) has no approved medical therapy in the
      United States and overactive bladder (OAB) therapy is limited to treatment with
      muscarinic antagonists (anti-muscarinics). SUI and OAB are characterised by high
      prevalence, a growing ageing population and a strong desire from sufferers and
      physicians for more effective treatment options. High patient numbers with low
      presentation rates characterizes sexual dysfunction in men and women. The
      introduction of Viagra in 1998 for treating male erectile dysfunction and the
      success of the phosphodiesterase type 5 inhibitor class (PDE5 inhibitor) have
      indicated the willingness of sufferers to seek treatment when an effective
      alternative to injections and devices is available. The main value of preclinical
      models in discovering new medicines is to predict clinical outcomes. This
      translation can be established relatively easily in areas of medicine where there
      are a large number of drugs with different underlying pharmacological mechanisms
      in clinical usage. However, apart from, for example, the use of PDE5 inhibitors
      to treat male erectile dysfunction and the use of anti-muscarinics to treat OAB,
      this clinical information is limited. Therefore, current confidence in existing
      preclinical models is based on our understanding of the biochemical,
      physiological, pathophysiological and psychological mechanisms underlying the
      conditions in humans and how they are reflected in preclinical models. Confidence
      in both the models used and the pharmacological data generated is reinforced if
      different models of related aspects of the same disorder generate confirmatory
      data. However, these models will only be fully validated in retrospect once the
      pharmacological agents they have helped identify are tested in humans.

PMID- 16465190
TI  - The effect of interaction between hepatitis C virus and cigarette smoking on the
      risk of hepatocellular carcinoma.
AB  - We evaluated the interaction between hepatitis C virus (HCV) and cigarette
      smoking on death from hepatocellular cancer in The Japan Collaborative Cohort
      Study. The odds ratio of death from HCC for smoking was 9.60 (1.50-61.35) and
      1.71(0.58-5.08) among anti-HCV positive and negative individuals, respectively.

PMID- 16465191
TI  - Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field
      radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase
      II study.
AB  - To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the
      addition of concurrent thoracic radiotherapy to a platinum-containing regimen is
      important. In the Netherlands, we initiated a multicenter, phase II study, of the
      combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m(-2)) and
      etoposide (2 x 50 mg orally for 5 days) combined with 45 Gy (daily fractions of
      1.8 Gy). The radiation was given to the involved field and concurrently with the
      second and third chemotherapy cycle. Patients with a partial or complete response
      received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999
      to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for
      toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in
      57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment
      related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis
      (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%)
      and lethargy (22%). The objective response rate was 92% (95% confidence interval
      (CI) 80-98%) with a median survival time of 19.5 months (95% CI 12.8-29.2). The 1
      , 2- and 5-year survival rate was 70, 47 and 27%, respectively. In field local
      recurrences occurred in six patients. Distant metastases were observed in 19
      patients of which 13 in the brain. This study indicates that combination
      chemotherapy with concurrent involved-field radiation therapy is an effective
      treatment for LS-SCLC. Despite PCI, the brain remained the most important site of
      recurrence.

PMID- 16465192
TI  - Targeted therapy for metastatic renal cell carcinoma.
AB  - Metastatic renal cell carcinoma (RCC) has historically been refractory to
      cytotoxic and hormonal agents; only interleukin 2 and interferon alpha provide
      response in a minority of patients. We reviewed RCC biology and explored the ways
      in which this understanding led to development of novel, effective targeted
      therapies. Small molecule tyrosine kinase inhibitors, monoclonal antibodies and
      novel agents are all being studied, and phase II studies show promising activity
      of sunitinib, sorafenib and bevacizumab. The results of phase III studies will
      determine the role of these agents in metastatic RCC.

PMID- 16465193
TI  - High incidence of late effects found in Hodgkin's lymphoma survivors, following
      recall for breast cancer screening.
AB  - Assessment of late effects in a cohort of female Hodgkin's lymphoma patients
      treated with mantle radiotherapy, identified from the DoH breast cancer screening
      recall showed high mortality and frequent undiagnosed abnormalities in tissues
      affected by radiotherapy. With increasing age, this patient group may suffer
      premature cardiac and respiratory morbidity.

PMID- 16465194
TI  - Expression of transketolase TKTL1 predicts colon and urothelial cancer patient
      survival: Warburg effect reinterpreted.
AB  - Tumours ferment glucose to lactate even in the presence of oxygen (aerobic
      glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose
      conversion to ribose for nucleic acid synthesis and glucose degradation to
      lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme
      reactions. We have detected upregulation of a mutated transketolase transcript
      (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like
      2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was
      correlated to invasive colon and urothelial tumours and to poor patients outcome.
      TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely
      to be caused by the internal deletion of conserved residues. We propose that
      TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage
      and a lactate-based matrix degradation. As inhibition of transketolase enzyme
      reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant
      target for novel anti-transketolase cancer therapies. We suggest an
      individualised cancer therapy based on the determination of metabolic changes in
      tumours that might enable the targeted inhibition of invasion and metastasis.

PMID- 16465187
TI  - Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and
      prostate.
AB  - 1 We have systematically reviewed the presence, functional responses and
      regulation of alpha(1)-, alpha(2)- and beta-adrenoceptors in the bladder, urethra
      and prostate, with special emphasis on human tissues and receptor subtypes. 2
      Alpha(1)-adrenoceptors are only poorly expressed and play a limited functional
      role in the detrusor. Alpha(1)-adrenoceptors, particularly their alpha(1A)
      subtype, show a more pronounced expression and promote contraction of the bladder
      neck, urethra and prostate to enhance bladder outlet resistance, particularly in
      elderly men with enlarged prostates. Alpha(1)-adrenoceptor agonists are important
      in the treatment of symptoms of benign prostatic hyperplasia, but their
      beneficial effects may involve receptors within and outside the prostate. 3
      Alpha(2)-adrenoceptors, mainly their alpha(2A)-subtype, are expressed in bladder,
      urethra and prostate. They mediate pre-junctional inhibition of neurotransmitter
      release and also a weak contractile effect in the urethra of some species, but
      not humans. Their overall post-junctional function in the lower urinary tract
      remains largely unclear. 4 Beta-adrenoceptors mediate relaxation of smooth muscle
      in the bladder, urethra and prostate. The available tools have limited the
      unequivocal identification of receptor subtypes at the protein and functional
      levels, but it appears that the beta(3)- and beta(2)-subtypes are important in
      the human bladder and urethra, respectively. Beta(3)-adrenoceptor agonists are
      promising drug candidates for the treatment of the overactive bladder. 5 We
      propose that the overall function of adrenoceptors in the lower urinary tract is
      to promote urinary continence. Further elucidation of the functional roles of
      their subtypes will help a better understanding of voiding dysfunction and its
      treatment.

PMID- 16465195
TI  - Comprehensive profiling and localisation of the matrix metalloproteinases in
      urothelial carcinoma.
AB  - The matrix metalloproteinases (MMPs) are endopeptidases which break down the
      extracellular matrix and regulate cytokine and growth factor activity. Several
      MMPs have been implicated in the promotion of invasion and metastasis in a broad
      range of tumours including urothelial carcinoma. In this study, RNA from 132
      normal bladder and urothelial carcinoma specimens was profiled for each of the 24
      human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key
      growth factors and their receptors using quantitative real time RT-PCR. Laser
      capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections
      was performed allowing accurate RNA extraction from either stromal or epithelial
      compartments. This study confirms the over expression in bladder tumour tissue of
      well-documented MMPs and highlights a range of MMPs which have not previously
      been implicated in the development of urothelial cancer. In summary, MMP-2, MT1
      MMP and the previously unreported MMP-28 were very highly expressed in tumour
      samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a
      significant positive correlation between transcript expression and tumour grade
      for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (P < 0.001). At the same
      confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour
      grade. LCM revealed that most highly expressed MMPs are located primarily within
      the stromal compartment except MMP-13 which localised to the epithelial
      compartment. This work forms the basis for further functional studies, which will
      help to confirm the MMPs as potential diagnostic and therapeutic targets in early
      bladder cancer.

PMID- 16465196
TI  - Validity and reliability of a new food frequency questionnaire compared to 24 h
      recalls and biochemical measurements: pilot phase of Golestan cohort study of
      esophageal cancer.
AB  - BACKGROUND: A pilot study was carried out to evaluate validity and
      reproducibility of a food frequency questionnaire (FFQ), which was designed to be
      used in a prospective cohort study in a population at high risk for esophageal
      cancer in northern Iran. METHODS: The FFQ was administered four times to 131
      subjects, aged 35-65 years, of both sexes. Twelve 24-h dietary recalls for two
      consecutive days were administered monthly during 1 year and used as a reference
      method. The excretion of nitrogen was measured on four 24-h urine samples, and
      plasma levels of beta-carotene, retinol, vitamin C and alpha-tocopherol was
      measured from two time points. Relative validity of FFQ and 24-h diet recall was
      assessed by comparing nutrient intake derived from both methods with the urinary
      nitrogen and plasma levels of beta-carotene, retinol, vitamin C and alpha
      tocopherol. RESULTS: Correlation coefficients comparing energy and nutrients
      intake based on the mean of the four FFQ and the mean of twelve 24-h diet recalls
      were 0.75 for total energy, 0.75 for carbohydrates, 0.76 for proteins and 0.65
      for fat. Correlation coefficients between the FFQ-based intake and serum levels
      of beta-carotene, retinol, vitamin C and vitamin E/alpha-tocopherol were 0.37,
      0.32, 0.35 and 0.06, respectively. Correlation coefficients between urinary
      nitrogen and FFQ-based protein intake ranged from 0.23 to 0.35. Intraclass
      correlation coefficients used to measure reproducibility of FFQ ranged from 0.66
      to 0.89. CONCLUSION: We found that the FFQ provides valid and reliable
      measurements of habitual intake for energy and most of the nutrients studied.

PMID- 16465197
TI  - Associations of anthropometric characteristics with blood cholesterol fractions
      among adults. The Greek EPIC study.
AB  - OBJECTIVE: To explore the independent associations of body height, body mass
      index (BMI), waist circumference and hip circumference with high-density
      lipoprotein-cholesterol (HDL-cholesterol) and non-high-density lipoprotein
      cholesterol (non-HDL-cholesterol), in a large general population sample. DESIGN:
      Cross sectional. SETTING: Urban and rural areas throughout Greece. SUBJECTS: In
      total,10 837 volunteers, 2034 men and 8803 women, aged 25-82 years, participants
      in the European Prospective Investigation into Cancer and Nutrition study (EPIC),
      who have never smoked and never been treated for dyslipidemia. INTERVENTIONS:
      None. RESULTS: The effect of height on non-HDL-cholesterol was opposite but in
      absolute terms almost as important as that of BMI with no gender interaction.
      Among women, hip circumference was inversely associated with non-HDL-cholesterol
      (standardized coefficient bst = -1.11, with standard error (s.e.)=0.42) and
      positively with HDL-cholesterol (bst = 0.85, s.e.= 0.12) whereas, waist
      circumference was inversely associated with HDL-cholesterol (bst = -1.16,
      s.e.=0.13) and strongly positively with non-HDL-cholesterol (bst = 8.83, s.e.=
      0.45). Among men, associations were generally weaker (in absolute terms by about
      50%) and for hip circumference the association with non-HDL-cholesterol was
      actually non significantly positive. CONCLUSIONS: Height was inversely associated
      with HDL and non-HDL-cholesterol implicating early life phenomena in the
      regulation of these variables. Larger hip circumference among women had
      beneficial effects on blood cholesterol fractions by increasing HDL-cholesterol
      and reducing non-HDL-cholesterol, whereas among men the relevant effects were
      less clear cut. The detrimental consequences of large waist circumference on both
      HDL (reduction) and non-HDL-cholesterol (increase) were also particularly marked
      among women. SPONSORSHIP: The European Prospective Investigation into Cancer and
      Nutrition (EPIC) is coordinated by the International Agency for Research on
      Cancer (World Health Organization) and supported by the Europe Against Cancer
      Program of the European Commission. The Greek segment of the EPIC study is also
      supported by the Greek Ministry of Health and the Greek Ministry of Education.
      This study was additionally supported by the fellowship 'Vassilios and Nafsika
      Tricha'.

PMID- 16465198
TI  - Use of body mass index to identify obesity-related metabolic disorders in the
      Chinese population.
AB  - OBJECTIVE: To identify the body mass index (BMI; in kg/m2) cutoff that predicts
      the risk for obesity-related metabolic disorders for the Chinese population.
      DESIGN: Community-based cross-sectional survey. SETTING: Rural regions of Jiangxi
      and Anhui provinces and an urban community of Jing'an District of Shanghai,
      China. SUBJECTS: Five hundred and twenty-nine non-pregnant, non-lactating urban
      and rural adults, aged 20-64 years without diagnosed diabetes. RESULTS: Subjects
      were divided into two groups: with or without obesity-related metabolic
      disorders, which was defined as having at least one of the following:
      hypertension, insulin resistance, high plasma triacylglycerol, low-density
      lipoprotein-cholesterol or glucose. Gender-specific multiple logistic regression
      analysis demonstrated a significant dose-response relationship between BMI and
      obesity-related metabolic disorders, after adjusting for potential confounders.
      The lowest BMI interval associated with significant risk for both men and women
      (odds ratios of 2.67 and 3.46, respectively) was that of 22.5-24.4. Receiver
      operating characteristic (ROC) curve analysis indicated that a BMI cutoff of 23
      had the best combination of sensitivity and specificity and the shortest distance
      in the ROC curve, with positive and negative predictive values of 0.6-0.7 in both
      genders. CONCLUSIONS: A BMI cutoff of 23 might be appropriate for use in
      identification of high risk of obesity-related metabolic disorders and serve as a
      public health action threshold in the Chinese population. SPONSORSHIP: Center of
      a Livable Future, John Hopkins Bloomberg School of Public Health.

PMID- 16465199
TI  - Depression and long chain n-3 fatty acids in adipose tissue in adults from Crete.
AB  - BACKGROUND: Only one study has investigated the relationship of essential fatty
      acids in the adipose tissue with depression in adults and suggested an inverse
      relationship between docosahexaenoic acid (22:6 n-3) (DHA) and depression.
      OBJECTIVE: To examine the relation between adipose tissue polyunsaturated fatty
      acids especially n-3 and n-6 fatty acids, an index of long-term or habitual fatty
      acid intake, and depression in adults. DESIGN: Cross-sectional study of healthy
      adults from the island of Crete. SETTING: The Preventive Medicine and Nutrition
      Clinic, University of Crete, Greece. SUBJECTS: A total of 130 healthy adults (59
      males, 71 females) aged 22-58 years. The sample was a sub-sample of the Greek
      ApoEurope study group. METHODS: Fatty acids were determined by gas chromatography
      in adipose tissue. Information about depression was obtained through the Zung
      Self-rating Depression Scale. RESULTS: Adipose tissue DHA was inversely related
      with depression. Multiple linear regression analysis taking into account the
      possible confounding effect of age, gender, body mass index, smoking and
      educational level confirmed this association. CONCLUSIONS: The inverse
      relationship between adipose DHA and depression in adults, replicates findings of
      a previous study. This relationship indicates that a low long-term dietary intake
      of DHA is associated with an increased risk for depression in adults.

PMID- 16465203
TI  - The Bcl-2 family of proteins and activation of the ICE-CED-3 family of proteases:
      a balancing act in apoptosis?

PMID- 16465200
TI  - Dietary patterns and risk of nonfatal acute myocardial infarction in Costa Rican
      adults.
AB  - OBJECTIVE: To investigate the association between dietary patterns and risk of a
      first nonfatal acute myocardial infarction (MI) in Costa Rican adults. DESIGN:
      Population-based case-control study. SUBJECTS: A total of 496 incident MI cases
      and 518 population-based randomly selected controls matched to the cases by age
      (+/-5 years), gender, and county of residence. Subjects were interviewed with a
      validated food frequency questionnaire. Dietary patterns were identified by
      factor analysis. Odds ratios (OR) and 95% confidence intervals (CI) were obtained
      using multivariate conditional logistic regression adjusted for several
      recognized risk factors for MI. RESULTS: Two diet patterns were identified,
      'vegetable' characterized by increased intake of vegetables and fruits, and
      'staple', characterized by an increased use of palm oil for cooking, and intake
      of refined grains (mostly white rice and white bread), legumes, coffee, added
      sugar, and red meat. Compared to the lowest quintile of the staple diet pattern,
      the highest quintile was associated with an increased risk of MI (OR: 3.70, 95%
      CI: 2.30-5.97). Adjusting for potential confounders did not change the results
      (OR: 3.53, 95% CI: 1.98-6.31). Consistently, an increasing staple pattern score
      was associated with lower HDL cholesterol (P for trend <0.02) and alpha-linolenic
      acid in adipose tissue (P for trend <0.0001). The vegetable pattern was not
      associated with MI. CONCLUSIONS: The staple dietary pattern of Costa Rican adults
      is associated with low plasma HDL cholesterol, low alpha-linolenic acid in
      adipose tissue, and increased risk of MI.

PMID- 16465204
TI  - Surviving Drosophila eye development.
AB  - During eye development, cell death interplays dynamically with events of
      differentiation to achieve the remarkably patterned structure of the fly compound
      eye. Mutations in genes that affect the normal developmental process can lead to
      excessive death of progenitor cells, or, alternatively, to the differentiation of
      supernumerary neurons, pigment and cone cells due to survival of cells that would
      normally be eliminated. These data reveal that eye development contains cell
      selection processes: only certain cells are selected to undergo differentiation,
      and supernumerary cells are actively eliminated by cell death pathways to achieve
      the highly ordered lattice of the eye. The final number of cells that comprise
      the eye is controlled through a balance of cell proliferation with proper cell
      differentiation and removal by cell death.

PMID- 16465205
TI  - Apoptosis in mammalian eye development: lens morphogenesis, vascular regression
      and immune privilege.
AB  - Formation of the mammalian eye requires a complex series of tissue interactions
      that result in an organ of exquisite sensory capability. The early steps in eye
      development involve extensive cell death associated with morphogenesis. Later,
      suppression of programmed cell death is essential for tissue differentiation and
      in the adult, the immune privileged status of the eye is maintained in part
      through factors that induce inflammatory cell apoptosis. Experimental evidence
      suggests that suppression of apoptosis in cells of the lens lineage by fibroblast
      growth factors is one component of their action during lens morphogenesis.
      Fibroblast growth factors are also required for normal lens fiber-cell
      differentiation. This includes a degenerative step for organelles that is
      presumably an adaptation for the clearance of light scattering elements from the
      optic axis. The process of organelle degeneration may be related to apoptosis in
      a few of its features. Actively-induced apoptosis becomes important for eye
      development as the temporary ocular vasculatures regress. This too, is presumably
      an adaptation for the disposal of cells that would disturb the passage of light
      to the retina. Ocular macrophages appear to be essential for the induction of
      apoptosis in the endothelial cells comprising the ocular vasculatures. In the
      adult, inflammatory cells entering the eye are exposed to the pro-apoptotic
      agents transforming growth factor-beta2 and Fas ligand. The expression of these
      molecules in the eye, and their action in killing inflammatory cells, has evolved
      as a means of preventing inflammation and subsequent loss of vision. Thus, the
      eye offers a unique and versatile system for studying the role of programmed cell
      death in lens development, vascular regression and immune privilege.

PMID- 16465206
TI  - Apoptosis of the mammalian retina and lens.
AB  - Although retinal neurons usually last the entire lifetime of an individual, many
      innate genetic and developmental errors and external stimuli can reduce their
      longevity leading to loss of visual acuity or blindness. Similarly, the lens,
      largely composed of denucleated fiber cells must remain transparent for life if
      vision is to remain clear. Apoptosis of retinal neurons and newly generated lens
      fiber cells contributes to retinal degeneration and cataract formation,
      respectively, in both humans and experimental mammals. The apoptosis is triggered
      by many stimuli in addition to inherited mutations and may be amenable to
      pharmacologic amelioration. These studies not only provide new clinical insights
      but also the opportunity to investigate the molecular pathways leading to
      apoptosis in an organ that is not required for survival. The eye, becomes,
      therefore, an important organ for evaluation of theories of apoptosis in vivo.

PMID- 16465207
TI  - Bcl-2 acts upstream of the PARP protease and prevents its activation.
AB  - Apoptosis has recently been extensively studied and multiple factors have been
      implicated in its regulation. It remains unclear how these factors are ordered in
      the cell death pathway. Here we investigate the relationship between the
      inhibitor of apoptosis, bcl-2, and the PARP protease, prlCE/CPP32, recently
      implicated in apoptosis. Using PARP proteolysis as an indicator of the activation
      of the PARP protease, we find that the chemotherapeutic agent, etoposide, induces
      apoptosis and PARP proteolysis in Molt4 cells as early as 4 h with cell death
      lagging behind this event. In contrast, Molt4 cells that over-express bcl-2 show
      no PARP proteolysis or cell death. In order to determine if bcl-2 inhibits the
      PARP protease or its activation, we developed a cell-free system. Using this
      system with extracts from etoposide-treated cells and purified bovine PARP, we
      demonstrate that extracts from bcl-2 over-expressing cells cause little or no
      PARP proteolysis. Whereas, extracts from control vector cells contain an active
      PARP protease. This protease is inhibited by the tetrapeptide ICE-like protease
      inhibitor, YVAD-chloromethylketone. Interestingly, this protease is not inhibited
      by the addition of purified bcl-2 protein. These results rule out that bcl-2
      directly inhibits the active protease or that it has an effect downstream of
      prlCE/CPP32 such as preventing access to the PARP substrate. These results also
      demonstrate a role of bcl-2 in interfering with an upstream signal required to
      activate the PARP protease and allow us to begin to order the components in the
      apoptotic pathway.

PMID- 16465208
TI  - Bcl-2 prevents activation of CPP32 cysteine protease and cleavage of poly (ADP
      ribose) polymerase and U1-70 kD proteins in staurosporine-mediated apoptosis.
AB  - Members of the the Bcl-2 and ICE/ced-3 gene families have been implicated as
      essential components in the control of the cell death pathway. Bcl-2
      overexpression can prevent programmed cell death (PCD) in different cell types.
      ICE/ced-3-like proteases are synthesized as pro-enzymes and are activated by
      limited proteolysis. When overexpressed in diverse cell types, they trigger PCD.
      Bcl-2 can inhibit PCD mediated by these proteases, although as yet it is not
      clear at what specific step in the cell death pathway the protein acts. Here, we
      demonstrate that CPP32/Yama/Apopain, a member of the ICE/Ced-3 gene family, is
      processed during staurosporine-induced apoptosis in HeLa cells and that
      concomitant with CPP32 activation, two other proteins, poly (ADP-ribose)
      polymerase (PARP) and the U1-70 K small ribonucleoprotein, also undergo
      proteolysis. Overexpression of Bcl-2 prevents cleavage of CPP32, PARP and U1-70 K
      and protects HeLa cells from PCD. These results demonstrate that Bcl-2 controls
      PCD, by acting upstream of CPP32/Yama/Apopain.

PMID- 16465209
TI  - The role of proteolysis in T cell apoptosis triggered by chelation of
      intracellular Zn2+.
AB  - Our previous work showed that chelation of intracellular Zn2+ with N,N,N',N'
      tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) induces apoptosis in rat
      thymocytes. The molecular mechanism involved in TPEN-triggered apoptosis remains
      unknown, except that it is a Ca2+-independent process. In the present study, we
      show that TPEN is unable to induce DNA fragmentation when added to isolated
      thymocyte nuclei, indicating that activation of a cytoplasmic component is
      essential for TPEN-induced apoptosis. Since cytosolic proteases related to
      interleukin-1beta-converting enzyme (ICE) are implicated as key activators of
      apoptosis in many different systems, we investigated the possible involvement of
      such proteases in TPEN-induced apoptosis. We found that treatment of thymocytes
      with TPEN caused an early degradation of nuclear poly(ADP-ribose) polymerase
      (PARP) and lamin prior to DNA cleavage. This could be inhibited by Z-Val-Ala-Asp
      chloromethylketone (VADcmk), an inhibitor of ICE-like proteases, but not by an
      inhibitor of Ca2+-regulated serine protease. Jurkat T cells also underwent
      extensive DNA fragmentation when incubated with TPEN. A cytosolic fraction,
      prepared from TPEN-treated Jurkat cells, produced extensive DNA fragmentation
      when applied to isolated thymocyte nuclei, whereas the cytoplasmic extract from
      untreated cells was ineffective either alone or together with TPEN. The apoptosis
      inducing activity in cytosolic fraction from TPEN-treated Jurkat cells was
      blocked by incubating cells in the presence of VADcmk or another inhibitor of ICE
      like proteases, Ac - Asp - Glu - Val - Asp-aldehyde (DEVD-CHO), which has been
      found to competitively inhibit CPP32/apopain. An increase in enzyme activity that
      cleaves Ac-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC), a fluorogenic
      substrate of CPP32/apopain and Mch3alpha, was detected in TPEN-treated thymocytes
      and Jurkat cells. In addition, the proteolytic cleavage of CPP32 resulting in the
      formation of two active fragments (p17 and p12) was observed in cytosolic
      extracts from TPEN-treated Jurkat cells, but not in extracts which were prepared
      from cells treated with TPEN in the presence of VADcmk or DEVD-CHO. Our results
      suggest that activation of cytosolic ICE-like proteases is an essential step in
      TPEN-induced apoptosis, and that CPP32/apopain is critically involved in this
      process.

PMID- 16465210
TI  - Flupirtine protects both neuronal cells and lymphocytes against induced apoptosis
      in vitro: implications for treatment of AIDS patients.
AB  - In the present study we demonstrate that flupirtine, an already clinically used,
      centrally acting, non-opiate analgesic agent, protects rat cortical neurons
      against HIV-gp120 induced apoptotic cell death. The drug was active at
      concentrations between 1 and 10 microg/ml. Furthermore we show inhibition of in
      vitro induced apoptosis in human blood mononuclear cells, using flupirtine.
      Induced apoptosis in peripheral blood mononuclear cells from healthy individuals
      and HIV-1 infected patients was reduced to approximately 50% after in vitro
      preincubation with flupirtine at concentrations between 0.1 and 10 microg/ml. The
      anti-apoptotic effect of flupirtine was restricted to CD3+ lymphocytes and in
      particular to CD4+ cells. Flupirtine does not affect uninduced apoptosis in human
      lymphocytes in vitro. The selective potential of flupirtine to reduce apoptosis
      without influencing uninduced apoptosis may qualify this compound as a potential
      drug in the therapy of HIV-1 infected patients.

PMID- 16465211
TI  - Intracellular free calcium related to apoptotic cell death in quail granulosa
      cell sheets kept in serum-free culture.
AB  - The relationship between apoptosis and resting intracellular free calcium
      ([Ca2+]i) was studied in serum-free cultures of granulosa cell sheets isolated
      from preovulatory quail follicles. Apoptosis was detected by acridine orange, in
      situ end-labeling of fragmented DNA and electron microscopy. [Ca2+]i was measured
      using fura-2. [Ca2+]i averaged 525 mM in freshly isolated sheets. In 24 h
      cultures no apoptosis was detected but [Ca2+]i became very dispersed, 20% of the
      sheets showing values above 1000 nM. At 48 h, apoptosis was obvious and [Ca2+]i
      remained dispersed. At 72 h, apoptosis and also the fraction of sheets with high
      [Ca2+]i were at their maximum. At 96 h apoptosis was subsiding and [Ca2+]i
      normalized. FSH depressed apoptosis and [Ca2+]i in the 72 h cultures. We conclude
      that at 24 h apoptosis is initiated at high [Ca2+]i foci. At later stages
      apoptosis is associated with high [Ca2+]i, but it is not clear whether this is
      cause or consequence.

PMID- 16465212
TI  - Apoptotic DNA fragmentation is detected by a semi-quantitative ligation-mediated
      PCR of blunt DNA ends.
AB  - Apoptosis is a form of programmed cell death (PCD) characterized by morphological
      changes and stereotypical DNA degradation described as a nucleosomal ;ladder'.
      However, nucleosomal ladders have only been clearly demonstrated in vertebrate
      tissues when large numbers of cells die in synchrony. Their absence may be
      explained by asynchronous death under physiological conditions, or by distinct
      molecular mechanisms. In this study, nucleosomal ladders were revealed by a
      ligation-mediated polymerase chain reaction (LMPCR), that amplifies DNA fragments
      with blunt, 5' phosphorylated ends. Numerous tissues from different organisms
      were examined which demonstrated that nucleosomal ladders (a) accompany
      physiological cell death in mammalian tissues where previously DNA fragmentation
      has not been detected; (b) are produced during invertebrate cell death; (c) are
      invariably generated via the production of blunt, 5' phosphorylated double strand
      breaks. These results suggest that PCD in multicellular organisms consistently
      involves apoptotic mechanisms and that the endonuclease activity is
      evolutionarily conserved.

PMID- 16465213
TI  - Progesterone withdrawal and RU-486 treatment stimulate apoptosis in specific
      uterine decidual cells.
AB  - Progesterone secretion is required for the growth and differentiation of
      endometrial stromal cells to form decidual cells. For many cells where a growth
      factor supports cell growth and proliferation, withdrawal of the growth factor
      initiates apoptosis. This study determined the time course and tissue location of
      apoptosis in deciduomal tissue after withdrawal of progesterone or injection of
      the antiprogestin, RU-486. Total DNA was isolated from decidual tissues at
      intervals after experimental treatments and separated electrophoretically.
      Internucleosomal DNA fragmentation characteristic of apoptosis was measured by
      quantitating levels of the 200 bp fragment. Apoptotic cells in tissue sections
      were detected by direct immunoperoxidase detection of digoxigenin-labeled DNA.
      Decidual apoptosis reached maximal levels at 12 h after withdrawal of
      progesterone or injection of RU-486. Increased concentrations of apoptotic cells
      were observed at the periphery of the growing deciduoma and in the
      antimesometrial deciduoma near the luminal epithelium after both treatments.
      These results suggest the withdrawal of progestin initiates apoptosis in cells at
      the early stages of decidualization.

PMID- 16465214
TI  - v-Crk, an effector of the nerve growth factor signaling pathway, delays apoptotic
      cell death in neurotrophin-deprived PC12 cells.
AB  - v-Crk is a member of a class of SH2 and SH3-containing adaptor proteins that have
      been implicated in regulating the TrkA receptor tyrosine kinase and potentiating
      Nerve Growth Factor (NGF)-mediated neurite outgrowth in pheochromocytoma (PC12)
      cells (Hempstead et al, Mol. Cell Biol. 14: 1964 - 1971). Given the fact that NGF
      induces both differentiation and survival by binding to TrkA, we examined the
      rate of apoptotic cell death elicited by NGF-withdrawal in native, v-Crk, and
      TrkA-expressing PC12 cells. While more than 50% of native PC12 cells underwent
      apoptosis within 48 h of NGF withdrawal, the v-Crk and TrkA-expressing cells were
      much more resistant to apoptosis under these conditions, whereby approximately 70
      and 95%, respectively, of the cells were alive. The ability of v-Crk to delay
      apoptosis required prior NGF-dependent differentiation, since naive
      undifferentiated v-Crk expressing PC12 cells or cells that express v-Crk mutants
      that are defective in NGF signaling were not protected from apoptosis during
      growth factor withdrawal. Moreover, addition of 50 ng/ml EGF to serum and NGF
      deprived v-Crk expressing cells, which also causes neurite outgrowth, promoted
      complete and long-term survival, although such EGF replacement had no
      neurotrophic effect on wild-type PC12 cells or PC12 cells overexpressing Human
      Bcl-2. These experiments suggest that v-Crk potentiation of a receptor tyrosine
      kinase under conditions of growth factor deprivation is essential for preventing
      apoptosis. However, unlike native PC12 cells, neither v-Crk or TrkA-expressing
      PC12 cells exhibited a G1 arrest when incubated for 2 weeks in NGF. Thus, v-Crk
      and TrkA may protect NGF deprived PC12 by preventing cell cycle arrest and hence
      an aborted entry into a defective cell cycle. Moreover, during NGF-withdrawal, v
      CrkPC12 cells exhibited down regulation in MAP kinase and JNK activities while in
      native cells, these activities increased within 6 - 8 h after NGF deprivation.
      Thus, unlike v-Crk-mediated augmentation of differentiation, sustained activation
      of MAP kinase may not be required for v-Crk-induced cell survival.

PMID- 16465215
TI  - Downregulation of Bcr-Abl in K562 cells restores susceptibility to apoptosis:
      characterization of the apoptotic death.
AB  - We examined the susceptibility of a variety of human leukemic cell lines to the
      induction of apoptosis. K562, a chronic myelogenous leukemic cell line which
      expresses the bcr-abl fusion gene, was found to be extremely resistant to
      apoptosis, irrespective of the inducing agent. This resistance can be attributed
      to the deregulated Abl kinase activity of bcr-abl, as downregulation of its
      expression using antisense oligodeoxynucleotides targeted to the beginning of the
      abl sequence in this chimeric gene rendered these cells susceptible to cytotoxic
      drug-induced apoptosis. Examination of the morphological and biochemical features
      of apoptosis in K562 cells revealed the typical membrane blebbing and chromatin
      condensation associated with this form of cell death. In situ TdT-mediated end
      labeling of the DNA revealed the presence of strand breaks in the treated cells
      and field inversion gel electrophoresis revealed the presence of large 10-50 kb
      fragments. However there was an absence of oligonucleosomal DNA fragmentation,
      whether or not Bcr-Abl was expressed. Thus, while inhibition of expression of Bcr
      Abl renders K562 cells susceptible to apoptosis, the absence of oligonucleosomal
      DNA fragmentation in these cells is independent of the function of this molecule.

PMID- 16465216
TI  - Prevention of apoptosis in J2E erythroid cells by erythropoietin: involvement of
      JAK2 but not MAP kinases.
AB  - The J2E erythroid cell line, transformed by retroviral v-raf/v-myc oncogenes,
      proliferates and differentiates in response to erythropoietin. Here we show that
      J2E cells undergo apoptosis rapidly after serum withdrawal and that only
      erythropoietin of seven growth factors tested, could protect the cells from
      death. The role of JAK2 and MAP kinases in transmitting viability signals
      initiated by erythropoietin was examined in these cells. Despite constitutive raf
      kinase activity, phosphorylation of MAP kinases fell after serum withdrawal.
      However, an antisense oligonucleotide strategy revealed that JAK2, but not the
      MAP kinases, was involved in transmitting signals to maintain the viability of
      J2E cells. Several cell cycle proteins and transcription factors were also
      studied; although c-jun rose sharply during apoptosis, erythropoietin could not
      suppress this increase. It was concluded that erythropoietin-induced protection
      from apoptosis involved JAK2, but not MAP kinases or c-jun.

PMID- 16465217
TI  - Apoptosis in the rat mammary gland and ventral prostate: detection of cell death
      associated genes using a coincident-expression cloning approach.
AB  - Apoptosis plays a striking role in the hormone-dependent involution of the
      mammary gland, but it has proved difficult to distinguish between the 'cell
      death' associated genes and the 'tissue remodelling' genes which are expressed
      concurrently. To identify cell death-associated genes, we have established a
      'coincidence analysis' based on the previously described 'RNA differential
      display' method of Liang and Pardee (1992). Coincidence analysis allows the
      detection of genes expressed during related processes in different organs and was
      employed here to identify transcripts in which expression patterns are seen to be
      associated with apoptosis during involution of both rat mammary- and the ventral
      prostate glands. That the coincidence analysis is a promising approach can be
      seen from the fact that while widely accepted apoptosis markers such as
      transglutaminase (Fesus et al, 1987; Strange et al, 1992) and sulfated
      glycoprotein-2 (Buttyan et al, 1989; Strange et al, 1992; Guenette et al 1994)
      exhibited similar expression in both regressing tissues, transcription of tissue
      remodelling enzymes was minimal in the involuting prostate. We describe here the
      characteristics of five clones isolated which show coincident expression during
      programmed cell death in mammary and prostate tissues. Partial sequence analysis
      revealed for three clones high homologies with previously described genes; the
      putative rat homolog of the growth arrest gene gas-1 (Schneider et al, 1988; Del
      Sal et al, 1992), an homolog of the mouse 'Integrin Associated Protein' (IAP)
      (Brown et al, 1990; Lindberg et al, 1993) and the sequence encoding for the
      'Allograft Inflammatory Factor' AIF-1 (Autieri et al, 1995; Utans et al, 1995).
      One clone displayed homology with an expressed human sequence tag and one clone
      unrelated to any known DNA sequence was isolated. The expression of these genes
      in involuting rat mammary and ventral prostate, was correlated with that in other
      organs and in situ hybridization was applied to establish that the secretory
      epithelial cells which undergo programmed cell death are the site of elevated
      expression during the course of involution. Furthermore, we conclude that the
      coincidence analysis approach described here could be easily applied to
      facilitate the characterization of gene expression i.e. for the detection and
      comparison of hormonally regulated genes in different organs.

PMID- 16465218
TI  - Zinc inhibits apoptosis upstream of ICE/CED-3 proteases rather than at the level
      of an endonuclease.
AB  - Apoptosis is commonly associated with DNA digestion, but it remains controversial
      as to which endonuclease is involved. The ability of zinc to inhibit DNA
      digestion in intact cells, and inhibit a Ca2+/Mg2+-dependent endonuclease in cell
      lysates, has been used frequently to suggest this is the endonuclease involved.
      However, zinc has many other effects on cells, and here it is shown that zinc
      also prevents many upstream events in apoptosis. These studies were performed in
      human ML-1 cells following incubation with etoposide. During apoptosis, these
      cells undergo intracellular acidification, increased accumulation of Hoechst
      33342, DNA digestion and chromatin condensation. Zinc inhibited all of these
      events. An upstream event in apoptosis is activation of ICE/CED-3 proteases which
      is commonly observed as proteolysis of a substrate protein, poly(ADP-ribose)
      polymerase (PARP). The ICE/CED-3 proteases are themselves activated by
      proteolysis, and this was detected here by cleavage of one family member CPP32.
      Zinc prevented cleavage of both CPP32 and PARP. We recently demonstrated that
      dephosphorylation of the retinoblastoma susceptibility protein Rb was a marker of
      an event even further upstream in apoptosis; zinc was also found to inhibit Rb
      dephosphorylation. Therefore, zinc must protect cells at a very early step in the
      apoptotic pathway, and not as a direct inhibitor of an endonuclease.

PMID- 16465219
TI  - Fas activates NF-kappaB and induces apoptosis in T-cell lines by signaling
      pathways distinct from those induced by TNF-alpha.
AB  - The p55 tumor necrosis factor (TNF) receptor and the Fas (CD95/APO-1) receptor
      share an intracellular domain necessary to induce apoptosis, suggesting they
      utilize common signaling pathways. To define pathways triggered by Fas and TNF
      alpha we utilized human CEM-C7 T-cells. As expected, stimulation of either
      receptor induced apoptosis and TNF-alpha-induced signaling included the
      activation of NF-kappaB. Surprisingly, Fas-induced signaling also triggered the
      activation of NF-kappaB in T cells, yet the kinetics of NF-kappaB induction by
      Fas was markedly delayed. NF-kappaB activation by both pathways was persistent
      and due to the sequential degradation of IkappaB-alpha and IkappaB-beta. However,
      the kinetics of IkappaB degradation were different and there were differential
      effects of protease inhibitors and antioxidants on NF-kappaB activation.
      Signaling pathways leading to activation of apoptosis were similarly separable
      and were also independent of NF-kappaB activation. Thus, the Fas and TNF
      receptors utilize distinct signal transduction pathways in T-cells to induce NF
      kappaB and apoptosis.

PMID- 16465220
TI  - Rearrangement of the tubulin and actin cytoskeleton during programmed cell death
      in Drosophila salivary glands.
AB  - During larva-to-pupa metamorphosis Drosophila salivary glands undergo programmed
      cell death by autophagocytosis. Although ultrastructure of Drosophila salivary
      glands has been extensively studied in the past, little is known about mechanism
      of programmed cell death, especially the role of the cytoskeleton. In this paper
      we describe changes in microtubule and actin filament network compared to the
      progress of DNA fragmentation and redistribution of acid phosphatase. In feeding
      and wandering larvae microtubules and actin filaments form regular networks
      localized mostly along the plasma membrane. The first major rearrangement of
      microtubules and actin filaments occurred when larvae everted spiracles and the
      glands shifted their secretion from saliva to mucoprotein glue (stage L1).
      Microtubule cytoskeleton became denser and actin filaments concentrated along
      cell boundaries. At the same time nuclei flattened and migrated into the
      microtubule-rich layer near the basal membrane. In late prepupae (8-10 h after
      P1) the microtubule network became fainter, and actin filaments appeared
      frequently deeper in cytoplasm, gradually concentrating around nuclei.
      Simultaneously large patches of acid phosphatase activity surrounded nuclei and
      shortly thereafter chromosomal DNA began to fragment. During the final collapse
      of the gland (early pupae, 13.5 h after formation of white puparium) cellular
      fragments and autophagic vacuoles contained a continuous F-actin lining and the
      microtubule network displayed signs of extensive degradation. The results are
      consistent with the hypothesis that, in Drosophila salivary glands, extensive
      autophagic activities target nuclei for degradation; that this process occurs
      late in the course of programmed cell death; and that it directly involves
      cytoskeletal structures which are altered far earlier during the course of cell
      death.

PMID- 16465221
TI  - Induction of differentiation and apoptosis by interferon-gamma in human
      neuroblastoma cells in vitro as a dual and alternative early biological response.
AB  - Interferon-gamma (IFN-gamma) has a well known differentiation-promoting activity
      on several neuroblastoma (NB) cell lines and has also been reported to induce
      apoptosis in different cellular models. We have investigated the potential of IFN
      gamma to trigger, besides differentiation, programmed cell death in NB cells and
      the relationship between these processes. Nine NB cell lines, characterized by
      different phenotypic and maturational features, were cultured in the presence of
      IFN-gamma (1000 IU/ml) for up to 5 days with either only one treatment at the
      start of the culture or renewing the culture medium (with or without IFN-gamma)
      every other day. Neuronal differentiation was assessed by evaluation of
      morphological changes and expression of mature cytoskeletal proteins, while
      apoptosis was evaluated at the desired times by fluorescent and electronic
      microscopy, DNA content analysis and DNA fragmentation assay. Our findings show
      that apoptosis is an early (mainly non post-differentiative) event and is much
      more evident following a single IFN-gamma administration. Moreover, IFN-gamma
      triggered apoptosis is independent of the cellular phenotype (schwannian or
      neuronal) and appears to be mutually exclusive with respect to differentiation at
      the single cell level. Our results strengthen the potential of IFN-gamma as a
      promising therapeutic agent for NB.

PMID- 16465222
TI  - Overexpressed Bcl-x(L) prevents bacterial superantigen-induced apoptosis of
      thymocytes in vitro.
AB  - bcl-x, a homologous gene of bcl-2, has an anti-apoptotic function and appears to
      play a critical role in the development of lymphoid systems. To investigate the
      effect of overexpressed Bcl-x(L) on the development of T lymphocytes, we
      established two lines of transgenic mice by using Emu-chicken bcl-x(L) (cbcl
      x(L)) transgene, where the cBcl-x(L) protein was expressed mainly in lymphoid
      cells. Although thymocytes and splenocytes from cbcl-x(L) transgenic mice are
      resistant to apoptosis in vitro, clonal deletion of thymocytes, recognizing
      endogenous self-superantigens in the thymus, still normally proceeded and no self
      reactive T cells were found in the spleen of the transgenic mice. To dissect
      clonal deletion, we utilized two in vitro models, thymocytes/antigen presenting
      cells co-culture system and fetal thymus organ culture system. In both, bacterial
      superantigen staphylococcus aureus enterotoxin B (SEB) induces apoptosis of T
      cells with Vbeta8+ T cell receptor (TCR) reacting to SEB, which mimics clonal
      deletion of self-reactive thymocytes in vivo. SEB-induced depletion of Vbeta8+ T
      cells from thymocytes when taken from the transgenic mice was effectively
      inhibited. The data might raise the possibility that cell death process involved
      in clonal deletion in the thymus is a form of apoptosis inhibited by Bcl-x(L).

PMID- 16465224
TI  - First International Symposium on Programmed Cell Death Shanghai, China, September
      8-12, 1996.

PMID- 16465225
TI  - Apoptosis in reproductive biology.

PMID- 16465226
TI  - Clinical aspects of male germ cell apoptosis during testis development and
      spermatogenesis.
AB  - Apoptosis appears to have an essential role in the control of germ cell number in
      testes. During spermatogenesis germ cell deletion has been estimated to result in
      the loss of up to 75% of the potential number of mature sperm cells. At least
      three factors seem to determine the onset of apoptosis in male germ cells: (1)
      lack of hormones, especially gonadotropins and androgens; (2) the specific stage
      in the spermatogenic cycle; (3) and the developmental stage of the animal.
      Although male germ cell apoptosis has been well characterized in various animal
      models, few studies are presently available regarding germ cell apoptosis in the
      human testis. The first part of this review is focused on germ cell apoptosis in
      testes of prepubertal boys, with special emphasis on apoptosis in normal and
      cryptorchid testes. A higher percentage of apoptotic spermatogonia was seen in
      the cryptorchid testes than in the scrotal testes. The hCG-treatment increased
      the number of apoptotic spermatogonia. The hCG-treatment-induced apoptosis in
      spermatogonia had severe long-term consequences in reproductive functions in
      adulthood. Increased apoptosis after hCG-treatment was associated with subnormal
      testis volumes, subnormal sperm density and pathologically elevated serum FSH.
      This finding indicates that increased apoptosis in spermatogonia in prepuberty
      leads to disruption of testis development. To evaluate the role of apoptosis in
      human adult testes, apoptosis was induced in seminiferous tubules that were
      incubated under serum-free conditions in the absence or presence of testosterone.
      Most frequently apoptosis was identified in spermatocytes. Occasionally some
      spermatids also showed signs of apoptosis. In short term incubations apoptosis
      was suppressed by testosterone. Our findings lead to the conclusion that
      apoptosis is a normal, hormonally controlled phenomenon in the human testis. The
      role of apoptosis in disorders of spermatogenesis remains to be established.

PMID- 16465227
TI  - The genes of cell death and cellular susceptibility to apoptosis in the ovary: a
      hypothesis.
AB  - Recent advances in the field of cell death, primarily derived from gene-transfer
      experiments and manipulation of tumor cell lines in vitro, have identified key
      genes responsible for determining whether or not a given cell will initiate
      apoptosis. However, comparatively less is known of the role that the products of
      these genes play in physiological settings of cell death. In the ovary, a
      tremendous level of normal cell death takes place in the germline throughout the
      later stages of fetal development. This process is responsible for setting the
      absolute number of oocytes ('eggs') available for subsequent development and
      ovulation during adult life. Interestingly, death remains the fate of the vast
      majority of oocytes that survive the waves of attrition during fetal life and are
      endowed in the post-natal ovary as primordial follicles. This pool of oocytes is
      lost indirectly as a consequence of the death of the somatic (granulosa) cells
      that, in the case of a small percentage of the total follicles, support and
      nourish the oocyte until its release at ovulation. Due to the magnitude of cell
      death that occurs normally within the female gonad during both fetal development
      and post-natal life, the ovary has proven to be an excellent model to study the
      role of cell death genes in a physiological setting of endocrine-regulated
      apoptosis. It is now known that a diverse spectrum of pro- and anti-apoptosis
      susceptibility genes, including members of the bcl-2 and CASP (ced-3/Ice) gene
      families, are expressed in germ cells and/or somatic cells of the ovary. Many,
      but not all, of these genes are regulated by specific survival factors, such as
      gonadotropins and growth factors, and changes in the temporal patterns of cell
      death gene expression suggest an intimate association exists between the products
      of these genes and activation of cellular suicide. Moreover, pathological oocyte
      destruction, such as that triggered by exposure of female germ cells to
      chemotherapeutic compounds or environmental toxicants, may also be dependent upon
      gene-driven apoptosis. As such, this review will discuss data supporting the
      hypothesis that the susceptibility of ovarian cells to death induction is
      dependent upon the pattern of cell death gene expression occurring within those
      cells prior to and/or concomitant with receipt of the stimulus for apoptosis.
      Elucidation of the relationship between germ cell loss and cell death genes may
      allow future intervention into the process of oocyte depletion associated with
      normal and pathophysiological reproductive senescence.

PMID- 16465228
TI  - Cell death in the gastrulating chick embryo: potential roles for tumor necrosis
      factor-alpha (TNF-alpha).
AB  - We have examined the expression of TNF-alpha and its receptors, TNFR1 and TNFR2,
      during gastrulation in the chick embryo, and have investigated the possible role
      of this factor in the control of cell death at this early stage of development.
      TNF-alpha, immunoreactive at approximately 17 kD, was found both in vivo and in
      vitro, most intensely associated with the cell surface and cytoskeleton of
      endoderm cells. TNFR2 was especially immunoreactive in endoderm cells of the
      marginal zone. TNFR1 was found in nuclei throughout the embryo. Embryos also
      showed widespread expression of both the bcl-2 and Bax gene products, which are
      both associated with cell death pathways. Intact embryos in culture were
      sensitive to the addition of TNF-alpha (approx. 110 ng/ml), responding by
      significantly increasing the incidence of DNA fragmentation in cells from all
      tissues of the embryo. This effect was abrogated by immunological pre-absorption
      of the cytokine. Cultured cells from these embryos also responded to the addition
      of agonistic antibodies to TNF-alpha receptors by increasing DNA fragmentation. A
      similar response to TNF-alpha antiserum by cultured cells appeared to be related
      to a concomitant decrease in cell-substratum adhesion caused by the antibody.
      Decreased cell adhesion, induced non-specifically with anti-integrin antiserum,
      also resulted in increased DNA fragmentation. TNF-alpha, synthesized and secreted
      by the embryo itself, may be able to exert a paracrine effect on the incidence of
      cell death in tissues of the embryo, and the cell death process may be related to
      the expression of bcl-2 and Bax gene products. The influence of TNF-alpha may be
      exerted by the activation of cell death signalling pathways directly, or
      indirectly through perturbation of the cytoskeleton or of integrin-mediated cell
      adhesion.

PMID- 16465229
TI  - Utilization of an in vitro assay to evaluate chromatin degradation by candidate
      apoptotic nucleases.
AB  - Apoptosis is commonly associated with the catabolism of the genome in the dying
      cell. The chromatin degradation occurs in essentially two forms: (1)
      internucleosomal DNA cleavage to generate oligonucleosomal-length fragments (180
      200 bp and multiples thereof), and (2) cleavage of higher order chromatin
      structures to generate approximately 30-50 Kb fragments. To investigate this
      component of apoptosis and identify the nuclease(s) responsible, we have
      developed and utilized an in vitro assay that recapitulates the genomic
      destruction seen during apoptosis in vivo and allows the simultaneous analysis of
      both forms of DNA degradation from the same sample. Using this assay we evaluated
      the digestion patterns of several candidate apoptotic nucleases: DNase I, DNase
      II, and cyclophilin (NUC18) as well as the bacterial enzyme micrococcal nuclease
      (not thought to be involved in apoptosis). Chromatin degraded by DNase I formed a
      smear of DNA on conventional static-field agarose gels and approximately amp;30 -
      50 Kb DNA fragments on pulsed field gels. In contrast, DNase II, at a
      physiologically relevant pH, had no effect on the integrity of HeLa chromatin in
      either analysis. Similar to DNase I, cyclophilin C produced only approximately 30
      50 Kb DNA fragments but did not generate internucleosomal fragments. In contrast,
      micrococcal nuclease generated both oligonucleosomal and approximately 30-50 Kb
      DNA fragments. Nuclear extracts from glucocorticoid-treated apoptotic thymocytes
      generated oligonucleosomal DNA fragments and the larger approximately 30-50 Kb
      DNA fragments, fully recapitulating both types of apoptotic DNA degradation.
      Previously, differential sensitivity of nucleases to inhibition by Zn2+ was used
      to argue that two distinct enzymes mediate approximately 30-50 Kb DNA cleavage
      and internucleosomal DNA degradation. While, the nuclease activity present in
      thymocyte nuclear extracts was differentially sensitive to inhibition by Zn2+
      during short term incubations it was not during prolonged digestions, suggesting
      that differences in DNA detection are likely to account for previous results.
      Together our studies show that none of the nucleases commonly associated with
      apoptosis could fully recapitulate the DNA degradation seen in vivo.

PMID- 16465230
TI  - Insulin and IGFs induce apoptosis in chick embryo retinas deprived of L
      glutamine.
AB  - In chick embryo retinas, cultured in serum-free medium lacking L-glutamine, IGF
      I, IGF-II and insulin induced apoptotic DNA fragmentation and cell death, IGF-I
      being the most efficacious compound. The apoptotic effect, which was particularly
      evident in retinas removed from 7-day-old chick embryos, declined with the age of
      the embryos and disappeared after day 11. Apoptosis appeared after a time lag of
      8 h and then increased with time up to 16 h. Cycloheximide, an inhibitor of
      protein synthesis, was capable of entirely abolishing apoptotic cell death. The
      effect induced by IGFs or insulin was suppressed by the addition of glutamine.
      Cytokine-mediated apoptosis was also observed after withdrawal of phosphate. We
      suggest that IGFs or insulin may produce, in retinas cultured in medium lacking L
      glutamine or phosphate, a conflict of signals that could be lethal for retinal
      cells.

PMID- 16465231
TI  - Transient G2M arrest and subsequent release of apoptotic and mitotic cells in
      vanadyl(4)-prepulsed human Chang liver cells.
AB  - The relationship between cell cycling and apoptosis/programmed cell death has
      been perceived as either checkpoint arrests or mitotic aberration where common
      pathways between mitosis and apoptosis seem suggested. We show here evidence
      implicating both perceptions of cell cycle involvement. The process was initiated
      by hydroxyl free radicals (OH*) generated intracellularly from internalized
      vanadyl(4). Intranuclear sequestration of vanadyl(4) was verified by nuclear
      microscopy. Resultant high oxidative reactivity in the nucleus was shown by the
      redox indicator methylene blue, suggesting direct oxidative damage to genomic
      DNA. Oxidative stress was further enhanced by depletion of glutathione which is
      the main cellular reducing agent. Genomic degradation and fragmentation was
      confirmed by flow cytometric evaluation of terminal deoxynucleotidyl transferase
      (TdT)-mediated 3'OH end-labelling (TUNEL) of DNA nicks, and cell cycle DNA
      profiling demonstrating sub-G1 (sub-2N) accumulation. With DNA degradation, there
      was a G2M transient with hyperdiploid right-shifting, consistent with G2 arrest.
      G2 arrest was subsequently 'released' with abolition of G2M and all other cell
      cycle phases except for a solitary sub-G1 (apoptotic) peak. The cytological
      profile of this 'release' phenomenon was initially marked by the appearance of
      clusters of mitotic and apoptotic cells. At later stages, the cell population was
      composed exclusively of nuclear ghosts, apoptotic cells, mitotic cells, and
      mitotic cells with both chromosomes and apoptotic condensations. Concurrent and
      conjoint expression of cell death and cell division as the exclusive process of
      an entire cell population refuted the notion of mutual exclusivity between life
      and death. Zn2+, an endonuclease inhibitor, abolished all observed cytological
      and DNA profile changes.

PMID- 16465232
TI  - Rapid and extensive lethal action of clofibrate on hepatoma cells in vitro.
AB  - Clofibrate, for a long time in use as a hypolipidemic drug, is a well known
      peroxisomal proliferator (PP) and hepatocarcinogen in rodents. We show here that
      in vitro 1 mM clofibrate induces a rapid and massive death of rat AH-130 hepatoma
      cells. Cell death was prominent already after 4 h of treatment, with a
      characteristic ;apoptotic' pattern by conventional microscopy. This was further
      supported by the pronounced chromatin condensation detectable on 4',6-diamine-2'
      phenylindole dihydrochloride (DAPI) staining, the clearcut internucleosomal DNA
      fragmentation on agarose-gel electrophoresis (ladder pattern), and the
      accumulation of markedly hypochromic cells observed in flow cytometric DNA
      histograms. Consistently with the apoptotic features of the process, some
      parameters commonly used to detect cell death, such as plasma membrane
      permeabilization to trypan blue or propidium iodide, lack of mitochondrial
      retention of rhodamine 123, or extracellular release of lactate dehydrogenase,
      were all virtually negative. However, these same parameters became markedly
      positive after 24 h of treatment, which was suggestive for the occurrence of
      ;secondary' necrosis among AH-130 cells. By a combination of flow cytometric
      parameters, after 4 h on 1 mM clofibrate only 41% of the AH-130 cells could still
      be categorized as viable (i.e., non-apoptotic and non-necrotic), while 46% of
      cells appeared apoptotic and 13% necrotic. At 24 h, 67% of cells were necrotic,
      20% apoptotic and only 13% non-apoptotic and non-necrotic. Apoptosis was also
      extensive in AH-130 cells treated with another PP such as nafenopin at 1 mM
      concentration and in human hepatoma HepG2 cells treated with clofibrate. By
      contrast, clofibrate did not cause apoptosis on primary rat hepatocyte cultures.
      These observations indicate that: (i) apart from their well-known cell growth
      promoting action, PPs such as clofibrate or nafenopin may exert a substantial
      cytotoxic action on targets such as the AH-130 or HepG2 hepatoma cells; (ii) this
      cell death evolves from an initial 'apoptotic' to an eventual ;necrotic' pattern;
      (iii) detection of cell death requires the adoption of a full panel of tests,
      adequate to cover the whole evolving death pattern, while such tests may even be
      substantially misleading whenever applied individually; (iv) the cytotoxicity of
      clofibrate and similar agents on normal and, particularly, tumoural cells may
      deserve careful reevaluation.

PMID- 16465233
TI  - Induction of apoptosis in neoplastic cells by depletion of vitamin B12.
AB  - Methionine synthase, a critical enzyme in deoxyribonucleotide biosynthesis for
      DNA replication, requires vitamin B12 as a cofactor. We have tested the
      hypothesis that depletion of cells of vitamin B12 would block growth of
      neoplastic cells and divert them into apoptosis and could form the basis of a new
      therapeutic strategy for cancer treatment. Using nitrous oxide to inactivate
      vitamin B12 we show that, in a variety of cell lines in vitro, methionine
      synthase is rapidly inhibited, the cells cease proliferation and undergo
      apoptosis. The kinetics of cell death, once started, are similar to those
      observed following methotrexate treatment or serum withdrawal. This is the first
      observation of apoptosis being induced following depletion of an essential
      metabolite as opposed to the more conventional strategy of adding a toxic drug to
      damage cells thereby triggering apoptosis. Moreover, vitamin B12 depletion has no
      effect on the nonproliferating cell population.

PMID- 16465234
TI  - Less death in the dying.
AB  - Diseases associated with aging are now the primary causes of death in developed
      countries. This is in part due to the long recognized exponential association of
      cancer with age and perhaps to a deterioration of the immune system with advanced
      age. Both prevention of tumorigenesis and immune function are critically
      dependent on apoptosis. In this study we examined apoptosis in mice of various
      age following gamma irradiation. We found a striking age-dependent decrease in
      radiation-induced apoptosis in splenic lymphocytes but not in colorectal
      epithelial cells. These observations may therefore provide a clue to the decline
      of immune function with age.

PMID- 16465235
TI  - Susceptibility to p53 dependent apoptosis correlates with increased levels of
      Gas2 and Gas3 proteins.
AB  - p53 dependent apoptosis is a critical regulator of tumorigenesis. In this paper
      we demonstrate that BALB/c cells transformed with a LT mutant perturbing pRb but
      not p53 functions (LT-2809) show unrestrained cell division under low serum
      condition which is actively counterbalanced by apoptosis. BALB/c cells
      transformed with a LT mutant perturbing p53 but not pRb functions (LT-K1), show
      similar unrestrained cell division but no evident signs of apoptosis when grown
      in low serum. Such apoptotic response of LT-2809 cells is characterised by
      increased expression of Gas2 which becomes proteolytically processed. Similarly
      Gas3 expression is markedly increased in LT-2809 cells with respect to LT-K1.
      Since both Gas2 and Gas3 have been previously associated with the apoptotic
      response at growth arrest, our observations suggest that they could also
      contribute to the regulation of cellular susceptibility to p53 dependent
      apoptosis.

PMID- 16465238
TI  - Ovarian follicular atresia: a model for apoptosis.

PMID- 16465236
TI  - 4th IUBMB conference on 'The Life and Death of the Cell'. Edinburgh 14-17th July
      1996.

PMID- 16465239
TI  - Expression of bak in S. pombe results in a lethality mediated through interaction
      with the calnexin homologue Cnx1.
AB  - Expression studies in the yeast S. pombe have been utilised to establish the
      basis for a genetic analysis designed to identify the lethal partners of the pro
      apoptotic proteins bak and bax. Bak expression in S. pombe is lethal and this
      lethality is rescued by co-expression of bcl-2 or bcl-x(L). S. pombe cells
      expressing bak have a terminal phenotype in which the majority of cells are
      blocked in the G1 phase of the cell cycle while the remainder of cells, unable to
      complete M-phase, mis-coordinate the timing of subsequent events in the cell
      cycle. Although bax expression in S. pombe gives rise to a slow growth phenotype,
      not a lethality, bax expressing cells display the same cell cycle phenotypes
      described for bak. Electron microscopy of cells expressing bak reveals a dramatic
      accumulation of large vesicular structures. A two-hybrid screen designed to
      identify S. pombe proteins which interact with bak, isolated the S. pombe
      calnexin homologue cnx1. Genetic analysis demonstrates that the Cnx1 domain which
      binds to bak in two-hybrid experiments, is necessary for bak lethality in S.
      pombe. This report identifies a lethal interacting partner for bak and the
      observations suggest a model for bak mediated lethality which can be tested in
      higher cells.

PMID- 16465240
TI  - Modification of the apoptotic-like effects of MBP protein overexpression in E.
      coli by fusion with 14-3-3 derived polypeptides.
AB  - Overexpression of even non-toxic proteins in bacteria causes a starvation-like
      response: the arrest of bacterial proliferation and apoptotic-like suicidal cell
      death. We have shown here that, as in the cells of higher organisms, these
      effects are accompanied by DNA degradation. The fusion with the bacterial MBP of
      a polypeptide, belonging to the 14-3-3 family and normally expressed in pumpkin
      (C. pepo), modifies the apoptotic-like effects of overexpression of this protein
      in E. coli. Fusion of the full length 14-3-3 protein with the MBP considerably
      slows down the DNA degradation caused by overexpression of the unmodified MBP.
      Overexpression of the construct containing a truncated version of the 14-3-3
      polypeptide causes immediate arrest of bacterial growth and rapid degradation of
      the chromosomal DNA. This result suggests that the DNA degradation in bacteria is
      an active process which can be modified to some extent by an endogenous protein.

PMID- 16465241
TI  - Activation of cyclin A-dependent kinases associated with WAF1 degradation during
      radiation-induced apoptosis.
AB  - We describe here the further characterisation of the radiation response of a pair
      of isogenic Burkitt's lymphoma cell lines which differ significantly in their
      susceptibility to radiation-induced apoptosis. In both cases a marked inhibition
      of cyclin A-dependent kinase activity was observed at 4 h post-irradiation which
      recovered to normal levels in the susceptible line by 12 h but remained inhibited
      in the resistant cell line. Under these conditions the cellular abundance of
      p58cyclinA and p33cdk2 did not significantly change in the two cell types and
      there was no evidence for phosphorylation changes in p33cdk2 which might account
      for the activity differences. In parallel with the changes in activity, p21WAF1
      increased initially in both cell lines, declined in the sensitive cell line as
      the activity recovered but remained high in the resistant cell line. This appears
      to be explained by a more rapid turn-over of p21WAF1 in the sensitive cell line
      and an increased association of p21WAF1 with cyclin kinase as determined by
      immunoprecipitation. These results implicate p21WAF1 in the regulation of cyclin
      dependent kinases during radiation-induced apoptosis, with persistence of induced
      p21WAF1 being associated with a more resistant phenotype.

PMID- 16465242
TI  - Expression of a defective mouse mammary tumor virus envelope glycoprotein
      precursor which binds stably to GRP78 within the lumen of the endoplasmic
      reticulum is associated with decreased glucocorticoid-induced apoptosis in mouse
      lymphoma cells.
AB  - Viral proteins inhibit apoptosis in host cells by a variety of mechanisms. This
      report proposes an additional mechanism, based on the interaction of a mutant
      mouse mammary tumor virus (MMTV) envelope glycoprotein precursor, Pr74, with the
      stress protein GRP78 (BiP) within the lumen of the endoplasmic reticulum (ER) (J.
      Biol. Chem. 268 7482-7488, 1993). We show that WEHI7.2 (W7.2) mouse lymphoma
      cells, which do not express Pr74, are more sensitive to cell death induction by
      the glucocorticoid hormone dexamethasone (dex), than W7MG1 cells, which were
      derived by infecting W7.2 cells with MMTV and therefore express Pr74 under
      control of the glucocorticoid-inducible MMTV promoter. Moreover, W7-ENV/N cells,
      derived by stably transfecting W7.2 cells with a constitutively expressed cDNA
      encoding mutant Pr74, were less sensitive to dex-induced cell death than control
      transfectant W7-ENV/- cells. Among multiple W7-ENV/N subclones, susceptibility to
      dex-induced cell death was inversely related to the level of Pr74 synthesis. The
      interaction of Pr74 with GRP78 induces an increase in GRP78 synthesis. Thus, the
      repression of cell death associated with Pr74 expression may be secondary to
      elevated synthesis of GRP78, a stress protein previously implicated in protection
      against cell death.

PMID- 16465243
TI  - The ability to cleave 28S ribosomal RNA during apoptosis is a cell-type dependent
      trait unrelated to DNA fragmentation.
AB  - Discrete cleavages within 28S rRNA divergent domains have previously been found
      to coincide with DNA fragmentation during apoptosis. Here we show that rRNA and
      DNA cleavages can occur independently in apoptotic cells, i.e. that the
      previously observed correlation is likely to be coincidental. In HL-60 cells,
      apoptosis with massive DNA fragmentation could be induced without any signs of
      rRNA cleavage. The opposite situation; rRNA cleavage without concomitant
      internucleosomal DNA fragmentation, was found in okadaic acid-treated Molt-4
      cells. Other leukemia cell lines underwent apoptosis either without (K562 and
      Molt-3) or with (U937) both forms of polynucleotide cleavage. In K562 cells
      transfected with a temperature-sensitive p53 mutant, internucleosomal DNA
      fragmentation but not 28S rRNA cleavage was inducible by wild-type p53
      expression. The absence of apoptotic rRNA cleavage in some cell types suggests
      that this phenomenon is tightly regulated and unrelated to DNA fragmentation or a
      presumed scheme for general macromolecular degradation in apoptotic cells.

PMID- 16465244
TI  - Modulation of the expression of Bcl-2 and related proteins in human leukemia
      cells by protein kinase C activators: relationship to effects on 1-[beta-D
      arabinofuranosyl]cytosine-induced apoptosis.
AB  - We have previously reported that pretreatment of HL-60 human promyelocytic
      leukemia cells with the non-tumor-promoting protein kinase C (PKC) activator
      bryostatin 1 potentiates induction of apoptosis by the antimetabolite 1-[beta-D
      arabinofuranosyl]cytosine (ara-C) (Biochem Pharmacol 47:839,1994). To determine
      whether this phenomenon results from altered expression of Bcl-2 or related
      proteins, Northern and Western analysis was employed to assess the effects of
      bryostatin 1 and other PKC activators on steady-state levels of Bcl-2, Bax, Bcl
      x, and Mcl-1 mRNA and protein. Pretreatment of cells for 24 h with 10 nM
      bryostatin 1, or, to a lesser extent, the stage-1 tumor-promoter phorbol
      dibutyrate (PDB) significantly potentiated apoptosis induced by ara-C (100
      microM; 6 h); in contrast, equivalent exposure to the stage-2 tumor promoter,
      mezerein (MZN), which, unlike bryostatin 1, is a potent inducer of
      differentiation in this cell line, failed to modify ara-C-related cell death.
      Neither bryostatin 1 nor PDB altered expression of bcl-2/Bcl-2 over this time
      frame. In contrast, MZN down-regulated bcl-2 mRNA levels, but this effect was not
      accompanied by altered expression of Bcl-2 protein. None of the PKC activators
      modified expression of Bax or Bcl-x(L) mRNA or protein; levels of Bcl-x(S) were
      undetectable in both treated and untreated cells. However, expression of Mcl-1
      mRNA and protein increased modestly after treatment with either bryostatin 1 or
      PDB, and to a greater extent following exposure to MZN. Combined treatment of
      cells with bryostatin 1 and MZN resulted in undiminished potentiation of ara-C
      mediated apoptosis and by antagonism of cellular maturation. These effects were
      accompanied by unaltered expression of Bcl-2, Bax, and Bcl-x(L), and by a further
      increase in Mcl-1 protein levels. When cells were co-incubated with bryostatin 1
      and calcium ionophore (A23187), an identical pattern of expression of Bcl-2
      family members was observed, despite the loss of bryostatin 1's capacity to
      potentiate apoptosis, and the restoration of its ability to induce
      differentiation. Finally, treatment of cells with bryostatin 1+/-ara-C (but not
      ara-C alone) resulted in a diffuse broadening of the Bcl-2 protein band, whereas
      exposure of cells to taxol (250 nM, 6 h) led to the appearance of a distinct Bcl
      2 species with reduced mobility, phenomena compatible with protein
      phosphorylation. Together, these findings indicate that the ability of bryostatin
      1 to facilitate drug-induced apoptosis in human myeloid leukemia cells involves
      factors other than quantitative changes in the expression of Bcl-2 family
      members, and raise the possibility that qualitative alterations in the Bcl-2
      protein, such as phosphorylation status, may contribute to this capacity. They
      also suggest that increased expression of Mcl-1 occurs early in the pre
      commitment stage of myeloid cell differentiation, and that this event does not
      protect cells from drug-induced apoptosis.

PMID- 16465245
TI  - Internucleosomal DNA fragmentation is not obligatory for castration induced rat
      ventral prostate cell apoptosis in vivo.
AB  - Castrated male rats were treated with the reversible S1-phase cell cycle blocking
      drug, mimosine, and the effects of this drug on prostate cell apoptosis was
      characterized. At a single dose of mimosine (25 mg/kg/day), we found that the
      internucleosomal DNA fragmentation associated with apoptosis was partially
      suppressed in the rat ventral prostate at all early time points (24, 48 and 72 h)
      analyzed post-castration. This suppression was dose-dependent, and treatment with
      mimosine up to 150 mg/kg/day was sufficient to reduce the internucleosomal DNA
      fragmentation in the prostate by 90% at 72 h post-castration. Intriguingly, this
      drug did not suppress the induction of mRNAs for several apoptosis-associated
      gene products in the ventral prostate gland (bcl-2, p53, TGF-beta and SGP
      2/clusterin). Moreover, this treatment did not suppress the histological
      appearance of apoptotic bodies in the ventral prostate detectable by fast green
      staining of thin sections of tissue. The apoptotic bodies present in mimosine
      treated regressing ventral prostate tissues, however, were refractory to labeling
      by the in situ gap labeling method, further demonstrating lack of nuclear DNA
      fragmentation in the condensed nuclei of apoptotic cells. In summary, the cell
      cycle-blocking drug mimosine does not appear to affect the rate of apoptosis in
      the regressing rat ventral prostate gland. However, this drug was capable of
      suppressing the nuclear DNA fragmentation associated with androgen-regulated
      prostate cell apoptosis. These results support the concept that nuclear DNA
      fragmentation is not obligatory for apoptosis. Additionally, they imply that cell
      cycle movement from the G1/S-phase boundary might be important for the terminal
      DNA degradation associated with androgen-regulated prostate cell apoptosis.

PMID- 16465246
TI  - Phosphatidylserine plasma membrane asymmetry in vivo: a pancellular phenomenon
      which alters during apoptosis.
AB  - The distribution of phospholipids across the two leaflets of the plasma membrane
      is important for many cellular processes including phagocytosis and hemostasis.
      In the present study we investigated the in vivo plasma membrane distribution of
      the aminophospholipid phosphatidylserine in mouse embryos with a novel technique
      employing Annexin V, a Ca2+ dependent phosphatidylserine binding protein,
      conjugated to fluorescein isothiocyanate and biotin. Annexin V directly applied
      to cryostat sections labeled the plasma membrane of all cells at the interface.
      In contrast, Annexin V injected intracardially into viable mouse embryos labeled
      almost exclusively apoptotic cells. These apoptotic cells were visible in all
      tissues and derived from all germ layers. Our experiments demonstrate that
      phosphatidylserine is asymmetrically distributed between the two leaflets of the
      plasma membrane in virtually all cell types in vivo and that this asymmetry is
      lost early during apoptosis.

PMID- 16465247
TI  - Inorganic mercury modifies Ca2+ signals, triggers apoptosis and potentiates NMDA
      toxicity in cerebellar granule neurons.
AB  - Hg2+ (0.1 microM-0.5 microM) modified the Ca2+ signals elicited by either KCl or
      the glutamate-receptor agonist, N-methyl-D-aspartate (NMDA), in cerebellar
      granule cells (CGCs). Hg2+ enhanced the intracellular Ca2+ transient elicited by
      high K+ and prevented a complete recovery of the resting intracellular Ca2+
      concentration ([Ca2+]i) after either KCl or NMDA stimulation. Higher Hg2+
      concentrations (up to 1 microM) increased [Ca2+]i directly. Following the short
      term exposure to Hg2+, CGCs underwent apoptosis, which was identified by the
      cleavage of DNA into large (700-50 kbp) and oligonucleosomal DNA fragments, and
      by the appearance of typical apoptotic nuclei. Combined treatment with 0.1-0.3
      microM Hg2+ and a sublethal NMDA concentration (50 microM) potentiated DNA
      fragmentation and apoptotic cell death. When the exposure to Hg2+ was carried out
      in Ca2+-free media or in the presence of Ca2+ channel blockers (L-type or NMDA-R
      antagonists), the effects on signalling and apoptosis were prevented. Our results
      suggest that very low Hg2+ concentrations can trigger apoptosis in CGCs by
      facilitating Ca2+ entry through membrane channels.

PMID- 16465248
TI  - Regulated redistribution of calretinins in WiDr cells.
AB  - The calcium-binding protein calretinin and the alternatively spliced form
      calretinin-22k are expressed in the colon adenocarcinoma cell line WiDr. As
      calcium-binding proteins have been implicated to play a role in cell cycle
      control, proliferation and differentiation, the levels and intracellular
      localisation of these two proteins were investigated. The addition of 1,25
      dihydroxy vitamin D3 (10(-8) M) led to a transient translocation of calretinin
      22k into the nucleus, while the cell growth was not affected. The addition of
      sodium butyrate and hexamethylene bisacteamide which induce markers of enterocyte
      differentiation decreased the levels of both forms of calretinin more than 90%.
      The agents which induced differentiation also led to a substantial inhibition of
      3H-thymidine incorporation (>95%) which was paralleled by the disappearance of
      calretinins. We conclude that calretinin and calretinin-22k are associated with
      the proliferative status of WiDr cells and are almost completely absent in
      differentiated cells.

PMID- 16465249
TI  - Acylphosphatase is involved in differentiation of K562 cells.
AB  - The level of both isoforms of acylphosphatase was evaluated in the human
      erythroleukemia K562 cell line during differentiation. K562 cells were treated
      with PMA, which induces megakaryocytic differentiation, and with aphidicolin or
      hemin, which stimulate erythrocytic differentiation. While the MT isoform showed
      an average 10-fold increase independently of the differentiating agent used, only
      hemin treatment caused a similar increase of the CT isoform, suggesting a
      different role of the two isoforms in the cell. Treatment with either hemin or
      aphidicolin of K562 cells overexpressing the two acylphosphatase isoforms
      suggested the possibility that acylphosphatases play a role in the onset of
      differentiation.

PMID- 16465250
TI  - DATELINE: New York--The Cell Death Society's 'Mechanisms of cell death'. Queens
      College of CUNY, Flushing, New York, 12 October, 1996.

PMID- 16465251
TI  - Death in Capri--The Fourth Euroconference on Apoptosis.

PMID- 16465252
TI  - The early modern period in cell death.

PMID- 16465253
TI  - The growth of the cell death field: an analysis from the ISI-Science citation
      index.

PMID- 16465254
TI  - The tumor strikes back: new data on expression of the CD95(APO-1/Fas)
      receptor/ligand system may cause paradigm changes in our view on drug treatment
      and tumor immunology.

PMID- 16465255
TI  - Programmed cell death in procyclic Trypanosoma brucei rhodesiense is associated
      with differential expression of mRNAs.
AB  - Procyclic Trypanosoma brucei rhodesiense have a cell death mechanism which can be
      activated by an external signal, the lectin ConA, in vitro. ConA has been shown
      to cause profound changes in cellular morphology and induce fragmentation of
      nuclear DNA in T.b. rhodesiense which are characteristic of apoptosis, a form of
      programmed cell death (PCD) in other eukaryotic cells. RNA analysis of
      trypanosomes induced to undergo PCD revealed that RNA remains intact up to 48 h
      into the process, a time when nuclear DNA fragmentation has already started.
      Using the randomly amplified differentially expressed sequences polymerase chain
      reaction method, ConA-induced cell death in T.b. rhodesiense is shown to be
      associated with differential expression of mRNAs, including up regulation of
      mRNAs late in the death process. The results demonstrate that trypanosomes
      actively participate in their own destruction through a PCD process and confirm
      that cell death in trypanosomes is associated with de novo gene expression.

PMID- 16465256
TI  - Targeted expression of ced-3 and Ice induces programmed cell death in Drosophila.
AB  - CED-3 is a cysteine protease required for programmed cell death in the nematode,
      Caenorhabditis elegans, and shares a sequence similarity with mammalian ICE
      (interleukin-1beta converting enzyme) family proteases. Both CED-3 and ICE family
      proteases can induce programmed cell death in mammalian cells. Structural and
      functional similarities between CED-3 and ICE family proteases indicate that the
      mechanism of cell death is evolutionarily conserved, suggesting the presence of a
      similar mechanism involving CED-3/ICE-like proteases in Drosophila. Here we
      determined whether CED-3 or ICE functions to induce programmed cell death in
      Drosophila. We have generated transformant lines in which ced-3 or Ice is
      ectopically expressed using the GAL4-UAS system. Expression of CED-3 and ICE can
      elicit cell death in Drosophila and the cell death was blocked by coexpressing
      the p35 gene which encodes a viral inhibitor of CED-3/ICE proteases. Results
      support the idea that the mechanism of programmed cell death controlled by CED
      3/ICE is conserved among widely divergent animal species including Drosophila,
      and the system described provides a tool to dissect cell death mechanism
      downstream of CED-3/ICE proteases.

PMID- 16465257
TI  - Glutathione depletion in fibroblasts is the basis for apoptosis-induction by
      endogenous reactive oxygen species.
AB  - Our study aimed at clarifying the role of the intracellular concentration of
      reduced glutathione for induction of apoptosis in fibroblasts. Treatment of
      fibroblasts with buthionine sulfoximine (BSO) caused efficient depletion of
      intracellular reduced glutathione which was followed by substantial cell death.
      Based on the induction of membrane blebbing, chromatin condensation and DNA
      strand breaks, cell death was characterized as apoptosis. Apoptosis after
      glutathione depletion seemed to be induced by endogenous reactive oxygen species
      (ROS), as it was antagonized by the antioxidant catechol and the hydroxyl radical
      scavenger DMSO. Paracrine interaction between cells prevented ROS-induced
      apoptosis and therefore points to the existence of extracellular survival
      factors. Our data show that the apoptosis-inducing potential of endogenous ROS is
      controlled by the intracellular glutathione concentration and by paracrine
      survival factors.

PMID- 16465258
TI  - Involvement of 5-lipoxygenase in programmed cell death of cancer cells.
AB  - We investigated the involvement of 5-lipoxygenase activity in the early phases of
      programmed cell death (PCD) induced by H2O2 or retinoids in different human
      tumour cells (erythroleukaemia, neuroblastoma, melanoma). Apoptotic cells showed
      enhanced 5-lipoxygenase activity which was paralleled by decreased superoxide
      dismutase activity and increased light emission. Ultraweak luminescence, mainly
      due to membrane lipid peroxidation by lipoxygenase activation, increased in all
      cell lines tested within 10-15 min after induction of PCD, in a concentration and
      time-dependent manner. At the same time, we observed a significant increase in
      the intracellular steady state level of the 5-lipoxygenase metabolite leukotriene
      B4. Furthermore, 5-lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid was
      able to induce PCD in all cell lines tested. Conversely, the general lipoxygenase
      inhibitor nordihydroguaiaretic acid and the selective 5-lipoxygenase inhibitor
      caffeic acid protected the different tumour cells from H2O2-induced PCD to a
      similar extent. These results show the activation of the 5-lipoxygenase pathway
      in PCD of three different cancer cell lines.

PMID- 16465259
TI  - Differential role of tyrosine phosphorylation in the induction of apoptosis in T
      cell clones via CD95 or the TCR/CD3-complex.
AB  - Activated T cells undergo apoptosis when the Fas-antigen (APO-1, CD95) is ligated
      by Fas Ligand (FasL) or agonistic anti-Fas antibodies. Repeated stimulation of T
      lymphocytes via the TCR/CD3-complex induces activation-induced cell death (AICD)
      associated with FasL surface expression. FasL binding to Fas molecules triggers
      the Fas-dependent death signaling cascade. Since it is still controversial
      whether Fas-induced cell death is associated with tyrosine kinase activity, we
      investigated the tyrosine kinase activation requirements in anti-Fas antibody
      induced cell death and AICD in human T cell clones. We report that cell death
      triggered by anti-Fas antibody is not accompanied by an increase in tyrosine
      phosphorylation and cannot be blocked by inhibitors of protein tyrosine kinases
      (PTK). Under the same conditions, AICD of T cell clones is clearly associated
      with tyrosine kinase activation. In fact, semiquantitative RT-PCR analysis of
      FasL mRNA expression triggered in T cell clones via the TCR/CD3-complex revealed
      that tyrosine phosphorylation is required for functional FasL mRNA and surface
      expression.

PMID- 16465260
TI  - The avian transcription factor c-Rel is induced and translocates into the nucleus
      of thymocytes undergoing apoptosis.
AB  - This study investigates the involvement of the avian transcription factor c-Rel
      in thymocyte apoptosis occurring either in vivo or in organotypic culture. In
      vivo, only a few cortical thymocytes express the c-Rel protein. Their number,
      localization and morphology resemble that of apoptotic cells evidenced by TUNEL
      staining. In organotypic culture, the expression of c-Rel is induced in medullary
      thymocytes as apoptosis is triggered. This induction would be post
      transcriptional since no increase in the c-rel gene expression is detected.
      Moreover, c-Rel translocates into the nucleus of medullary thymocytes during the
      time course of apoptosis. This translocation is preceded by a decrease in ikba
      expression, the gene which encodes the avian homologue of IkappaBalpha.
      Altogether these results suggest that the proto-oncogene c-rel could take an
      active part in apoptosis of cortical thymocytes occurring in vivo during T-cell
      selection as well as in experimentally-induced apoptosis of medullary thymocytes.

PMID- 16465261
TI  - DATELINE Boston--the third IBC Annual International Conference on Apoptosis:
      practical applications and novel therapies. Boston, Massachusetts, November 20
      21, 1996.

PMID- 16465262
TI  - Mitochondria as the focus of apoptosis research.

PMID- 16465263
TI  - Apoptosis and necrosis: intracellular ATP level as a determinant for cell death
      modes.
AB  - Apoptosis and necrosis are two distinct modes of cell death with respective
      morphological characteristics. However, apoptosis and some forms of necrosis must
      share common steps since both modes of cell death can be suppressed by the anti
      apoptotic Bcl-2 protein and caspase inhibitors. Intracellular ATP levels have
      been implicated both in vitro and in vivo as a determinant of the cell's decision
      to die by apoptosis or necrosis.

PMID- 16465264
TI  - Energy supply and the shape of death in neurons and lymphoid cells.
AB  - Apoptosis and necrosis are considered as conceptually distinct forms of cell
      death. Nevertheless, there is increasing evidence that classical apoptosis and
      necrosis represent only the extreme ends of a wide range of possible
      morphological and biochemical deaths. The two classical types of demise can occur
      simultaneously in tissues or cell cultures exposed to the same stimulus, and
      often the intensity of the same initial insult decides the prevalence of either
      apoptosis or necrosis. This suggests that, while some early events may be common
      to both types of cell death, a downstream controller may be required to direct
      cells towards the organised execution of apoptosis. We have recently shown that
      intracellular energy levels and mitochondrial function are rapidly compromised in
      necrosis, but not in apoptosis of neuronal cells. Then, we went on to show that
      pre-emptying human T cells of ATP switches the type of demise caused by two
      classic apoptotic triggers (staurosporin and CD95 stimulation) from apoptosis to
      necrosis. Conditions of controlled intracellular ATP depletion, which was
      obtained by blocking mitochondrial and/or glycolytic ATP generation, were used in
      combination with repletion of the cytosolic ATP pool with glucose to redirect the
      death program towards apoptosis or necrosis. At least two distinct steps, the
      typical nuclear degradation, and the expression of annexin V-recognisable
      determinants on the cell surface require sufficient ATP generation. This suggests
      that some upstream regulators of cell death may be common to both types of cell
      demise, whereas yet unknown downstream processes decide its shape and the
      implications for the neighbouring tissue.

PMID- 16465265
TI  - Mitochondrial implication in apoptosis. Towards an endosymbiont hypothesis of
      apoptosis evolution.
AB  - Recent evidence indicates that a profound alteration in mitochondrial function
      constitutes an obligatory early event of the apoptotic process. The molecular
      mechanism accounting for this alteration is mitochondrial permeability transition
      (PT). PT is both sufficient and necessary for apoptosis to occur. Experiments
      performed in cell-free systems of apoptosis demonstrate that mitochondria
      undergoing PT release protease activators that can trigger nuclear manifestations
      of apoptosis. Bcl-2 and its homologs are endogenous regulators of PT. It appears
      that some types of necrosis, those inhibited by Bcl-2, involve PT. If PT is a
      rate-limiting event of both apoptosis and necrosis, then downstream events
      including caspase activation and the bioenergetic consequences of PT must
      determine the choice between both modes of cell death. PT without caspase
      activation would cause necrosis. These findings have important implications for
      the comprehension of the apoptotic process, for the dichotomy between apoptosis
      and necrosis, and for the phylogeny of programmed cell death. Apoptosis may have
      evolved together with the endosymbiotic incorporation of aerobic bacteria (the
      precursors of mitochondria) into ancestral unicellular eukaryotes.

PMID- 16465266
TI  - Role of proteases in activation of apoptosis.
AB  - Programmed cell death, or apoptosis, is a physiological cell suicide mechanism,
      which is triggered in the cells by different stimuli. It has been shown that
      proteases play a significant role both in the target cell killing by cytotoxic
      lymphocytes and in the TNF- or anti-Fas-induced cell death. The proteases
      involved in the early (induction) and late (cell self-destruction) stages of
      apoptosis are reviewed. It is suggested that the late stages are connected with
      the activation of a cascade of intracellular proteases, which leads to massive
      protein destruction. It is likely that the protein destruction is mainly designed
      for preventing autoimmune response to proteins released from dying cells.

PMID- 16465267
TI  - Lack of 'tissue' transglutaminase protein cross-linking leads to leakage of
      macromolecules from dying cells: relationship to development of autoimmunity in
      MRLIpr/Ipr mice.
AB  - Genetic defects of the CD95 (Fas/Apo-1) receptor/ligand system, has recently been
      involved in the development of human and murine autoimmunity. We investigated
      whether a deregulation of the ;tissue' transglutaminase (tTG), a multifunctional
      enzyme which is part of the molecular program of apoptosis, may act as a cofactor
      in the development of autoimmunity. We found that MRLlpr/lpr, which are
      characterized by a defect in the CD95 receptor and suffer of a severe systemic
      lupus erythematosus-like disease, produce large amounts of circulating tTG
      autoantibodies. This phenomenon is paralleled by an abnormal accumulation of an
      inactive enzyme protein in the accessory cells of lymphoid organs. To investigate
      the molecular mechanisms by which tTG inhibition may contribute to the
      development of autoimmunity we generated a cell culture model system consisting
      of L929 cells stably transfected with a full length tTG cDNA. When L929 cells
      were killed by Tumor Necrosis Factor alpha (TNFalpha) a pronounced release of DNA
      and Lactate Dehydrogenase (LDH) was observed. Overexpression of tTG in these
      cells largely prevented the leakage of macromolecules determined by TNFalpha
      treatment, an effect which is abolished by inactivating the enzyme cross-linking
      activity by a synthetic inhibitor. These in vitro observations provided the basis
      to explain the increased levels of plasmatic LDH we detected in MRLlpr/lpr mice.
      These data suggest that lack of an active tTG may represent a cofactor in the
      development of autoimmunity.

PMID- 16465268
TI  - Caspase-4 and caspase-5, members of the ICE/CED-3 family of cysteine proteases,
      are CrmA-inhibitable proteases.
AB  - Proteases of the caspase family are implicated in mammalian apoptosis and
      constitute a protease cascade. We characterized caspase-4 (TX/ICH-2/ICErelII) and
      caspase-5 (ICErelIII/TY), which are most closely related to caspase-1 (ICE) among
      the caspase family. Although overexpression of caspase-4 and caspase-5 induced
      apoptosis, confirming previous observations, this apoptosis was not inhibited by
      a caspase-1-specific tetrapeptide inhibitor (Ac-YVAD-CHO), suggesting that
      caspase-4 and caspase-5 have different substrate specificities from caspase-1 and
      also that caspase-4- and caspase-5-induced apoptosis is not mediated by caspase
      1. CrmA, a cowpox virus-derived caspase-1 inhibitor that prevents apoptosis
      induced by various stimuli, was cleaved by caspase-4 and caspase-5, and inhibited
      their proteolytic activity as assessed by cleavage of pro-caspase-3 (pro
      CPP32/Yama/apopain). Thus, caspase-4 and caspase-5 are CrmA-inhibitable proteases
      like caspase-1 and might be involved in apoptosis.

PMID- 16465269
TI  - Inhibitors of arachidonic acid metabolism reduce DNA and nuclear fragmentation
      induced by TNF plus cycloheximide in U937 cells.
AB  - U937 human myeloid leukemia cells are induced to apoptosis by tumour necrosis
      factor (TNF) plus cycloheximide (CHX). We have analysed the effect of various
      inhibitors of the arachidonic acid (AA) metabolism on several features of this
      process. The formation of high molecular weight and oligonucleosomal DNA
      fragments as well as nuclear fragmentation were reduced by inhibitors of 5
      lipoxygenase (BWA4C and BWB70C), 5-LO activating protein (MK-886), and cytosolic
      PLA2 (AACOCF3). None of these agents blocked the morphological changes detected
      by microscopy or flow cytometry, phosphatidylserine exposure on the cell surface
      or Caspase 3-like activation. AA also induced nuclear fragmentation at a
      concentration of 1-20 microM. However, the mechanisms by which these inhibitors
      act, remain unexplained since there was no 5-LO expression in the U937 cells and
      no AA release followed their stimulation with TNF plus CHX.

PMID- 16465270
TI  - Evidence against the hypothesis that BCL-2 inhibits apoptosis through an anti
      oxidant effect.
AB  - We contrasted possible protection against apoptosis afforded by either BCL-2
      expression or anti-oxidant inhibitors in the same tumor target challenged by two
      distinct triggers of apoptosis. Exposure of L929 fibroblasts to tumor necrosis
      factor (TNF) or etoposide (VP-16) induced apoptotic death with similar kinetics.
      Enforced expression of BCL-2 significantly protected against apoptosis induced by
      VP-16 but had no effect against TNF-induced apoptosis. In contrast, the anti
      oxidants desferrioxamine, butylated hydroxyanisol and N-acetyl cysteine all
      inhibited TNF-induced apoptosis in a concentration-dependent fashion. Although
      exposure to VP-16 resulted in a significant generation of intracellular
      oxyradicals, the above three anti-oxidant inhibitors had no effect on VP-16
      induced apoptotic death. Interestingly, enforced expression of BCL-2 also
      inhibited the ability of VP-16 to generate oxy-radicals and to depress
      intracellular glutathione levels. These results indicate that BCL-2 can exert
      anti-oxidant effects but argue against the hypothesis that these effects are
      critical to its protection against apoptosis.

PMID- 16465271
TI  - Presence of a functional vitamin D receptor does not correlate with vitamin D3
      phenotypic effects in myeloid differentiation.
AB  - Although VDR is expressed in all the acute myeloid leukemia cell populations
      studied, most of these leukemias do not exhibit any phenotypic response when
      exposed to VD. To determine whether VD resistance is related to an altered VDR
      function, we performed an analysis of VDR expression, phosphorylation, DNA
      binding capacity and transactivation activity in several leukemic myeloid cell
      lines arrested at different levels of maturation. Our results indicate that VD
      induces a clear phenotypic effect, i.e. terminal monocytic differentiation, only
      in leukemic cells of M2/M3 (intermediate myeloblasts) and M5 (monoblasts) types
      but not in erythroid precursor cells, early leukemic myeloblasts (M0/M1 type) and
      promyelocytes (M3 type). VDR expression and function are evident in all the
      nuclear extracts obtained from the different myeloid cell lines after 12 h of VD
      treatment, but VD activation of monocytic differentiation is limited to a narrow
      differentiation window characterized by the M2 type myeloid cellular context.

PMID- 16465273
TI  - Mitochondrial signals and energy requirement in cell death.

PMID- 16465274
TI  - Excitotoxicity.

PMID- 16465272
TI  - Evidence that DNA fragmentation in apoptosis is initiated and propagated by
      single-strand breaks.
AB  - Apoptosis is characterised by the degradation of DNA into a specific pattern of
      high and low molecular weight fragments seen on agarose gels as a distribution of
      sizes between 50-300 kb and sometimes, but not always, a ladder of smaller
      oligonucleosomal fragments. Using a 2D pulsed field-conventional agarose gel
      electrophoresis technique, where the second dimension is run under either normal
      or denaturing conditions, we show that single-strand breaks are introduced into
      DNA at the initial stages of fragmentation. Using single-strand specific nuclease
      probes we further show that the complete fragmentation pattern, including release
      of small oligonucleosomal fragments can also be generated by a single-strand
      endonuclease. Three classes of sites where single-strand breaks accumulate were
      identified. The initial breaks produce a distribution of fragment sizes (50 kb to
      >1 Mb) similar to those generated by Topoisomerase II inhibitors suggesting that
      cleavage may commence at sites of attachment of DNA to the nuclear matrix. A
      second class of rare sites is also cut further reducing the size distribution of
      the fragments to 50-300 kb. Thirdly, single-strand breaks accumulate at the
      linker region between nucleosomes eventually causing double-strand scissions
      which release oligonucleosomes. These observations further define the properties
      of the endonuclease responsible for DNA fragmentation in apoptosis.

PMID- 16465275
TI  - Keystone 1997: return of the worm. Temarron, Colorado, February 18-23, 1997.

PMID- 16465276
TI  - Dying for a living: plants do it too.

PMID- 16465277
TI  - Programmed cell death during plant growth and development.
AB  - This review describes programmed cell death as it signifies the terminal
      differentiation of cells in anthers, xylem, the suspensor and senescing leaves
      and petals. Also described are cell suicide programs initiated by stress (e.g.,
      hypoxia-induced aerenchyma formation) and those that depend on communication
      between neighboring cells, as observed for incompatible pollen tubes, the
      suspensor and synergids in some species. Although certain elements of apoptosis
      are detectable during some plant programmed cell death processes, the
      participation of autolytic and perhaps autophagic mechanisms of cell killing
      during aerenchyma formation, tracheary element differentiation, suspensor
      degeneration and senescence support the conclusion that nonapoptotic programmed
      cell death pathways are essential to normal plant growth and development.
      Heterophagic elimination of dead cells, a prominent feature of animal apoptosis,
      is not evident in plants. Rather autolysis and autophagy appear to govern the
      elimination of cells during plant cell suicide.

PMID- 16465278
TI  - Programmed senescence of plant organs.
AB  - The senescence of plant organs associated with reproductive development has been
      studied extensively during the past century, and it has long been recognized that
      this type of death is internally programmed. The regulation of organ senescence
      as well as its biochemical and genetic determinants has been an historically rich
      area of research. Certain plant hormones have been implicated as regulators or
      modulators of organ senescence and many of the biochemical pathways associated
      with the senescence syndrome have been elucidated. The genetic basis of organ
      senescence has also been well established by the identification of mutations that
      impair the senescence program and recently, transgenic plants have been used to
      critically determine the role of specific enzymes and hormonal signals in
      mediating programmed senescence of plant organs. Here, we review the current
      understanding of the processes that regulate leaf, flower and fruit senescence,
      emphasizing the role that programmed organ senescence plays in the adaptive
      fitness of plants.

PMID- 16465279
TI  - The hypersensitive response and the induction of cell death in plants.
AB  - The hypersensitive response, or HR, is a form of cell death often associated with
      plant resistance to pathogen infection. Reactive oxygen intermediates and ion
      fluxes are proximal responses probably required for the HR. Apoptosis as defined
      in animal systems is, thus far, not a strict paradigm for the HR. The diversity
      observed in plant cell death morphologies suggests that there may be multiple
      pathways through which the HR can be triggered. Signals from pathogens appear to
      interfere with these pathways. HR may play in plants the same role as certain
      programmed cell deaths in animals with respect to restricting pathogen growth. In
      addition, the HR could regulate the defense responses of the plant in both local
      and distant tissues.

PMID- 16465280
TI  - Programmed cell death during vascular system formation.
AB  - Vascular plants have vessels and tracheids composed of dead tracheary elements.
      Differentiation of procambial or cambial cells to tracheary elements is a typical
      example of programmed cell death in higher plants. Recent studies on tracheary
      element differentiation, in particular with an in vitro differentiation system,
      have revealed a unique cell death process which differs from apoptosis. Herein I
      summarize the present knowledge about the induction of cell death, the
      morphological features of cell death, and the mechanism of autolysis, including
      the involvement of a DNase and cysteine proteases, during tracheary element
      differentiation.

PMID- 16465281
TI  - Mycotoxins reveal connections between plants and animals in apoptosis and
      ceramide signaling.
AB  - Plants undergo programmed cell death during development and disease in contexts
      that are functionally analogous to apoptosis in animals. Recent studies involving
      plant cell death induced by mycotoxins, pathogens and lethal mutations along with
      the cell-autonomous death during development now point to several conserved
      connections to apoptosis in animals. Morphological markers indicative of
      apoptosis recently reported in plants include TUNEL positive cells, DNA ladders,
      Ca2+-activated nucleosomal DNA cleavage, and formation of apoptotic-like bodies
      that occur in some but not all situations involving ordered cell death. In
      parallel studies with animal and plant cells treated with sphinganine analog
      mycotoxins our results indicate that the induction and inhibition of death may be
      mediated by ceramide-linked signaling systems. The presence and significance of
      ceramide-linked second messenger systems is well documented in animals but is
      virtually unknown in plants. Further research will discern the manner in which
      the important function of programmed cell death is conserved as well as diverged
      between the two kingdoms.

PMID- 16465282
TI  - Apoptotic cell death and cytokine dysregulation in human immunodeficiency virus
      infection: pivotal factors in disease progression.
AB  - The progressive loss of CD4 T lymphocyte is patognomonic of Human
      Immunodeficiency Virus (HIV) infection and results in immunodeficiency and the
      appearance of acquired immunodeficiency syndrome (AIDS)-defining pathologies.
      Although a percentage of CD4 T lymphocytes is destroyed directly by HIV
      infection, a much higher proportion of lymphocytes remains uninfected and
      therefore must be destroyed by mechanisms not directly involving viral infection.
      One such mechanism is apoptotic T cell death (ATCD). ATCD in HIV infection has
      been shown to be: 1) secondary to cross-linking of CD4 by viral proteins; 2)
      mediated by both APO-1/Fas and lymphotoxin (LT); and 3) differentially modulated
      by type 1 and type 2 cytokines. We will briefly analyze the experimental
      evidences suggesting that ATCD contributes significantly to the
      immunopathogenesis of HIV/AIDS via depletion of CD4+ T cells.

PMID- 16465283
TI  - Cleavage of cytoskeletal proteins by caspases during ovarian cell death: evidence
      that cell-free systems do not always mimic apoptotic events in intact cells.
AB  - Several lines of evidence support a role for protease activation during
      apoptosis. Herein, we investigated the involvement of several members of the CASP
      (cysteine aspartic acid-specific protease; CED-3- or ICE-like protease) gene
      family in fodrin and actin cleavage using mouse ovarian cells and HeLa cells
      combined with immunoblot analysis. Hormone deprivation-induced apo-ptosis in
      granulosa cells of mouse antral follicles incubated for 24 h was attenuated by
      two specific peptide inhibitors of caspases, zVAD-FMK and zDEVD-FMK (50-500
      microM), confirming that these enzymes are involved in this paradigm of cell
      death. Proteolysis of actin was not observed in follicles incubated in vitro
      while fodrin was cleaved to the 120 kDa fragment that accompanies apoptosis.
      Fodrin, but not actin, cleavage was also detected in HeLa cells treated with
      various apoptotic stimuli. These findings suggest that, in contrast to recent
      data, proteolysis of cytoplasmic actin may not be a component of the cell death
      cascade. To confirm and extend these data, total cell proteins collected from
      mouse ovaries or non-apoptotic HeLa cells were incubated without and with
      recombinant caspase-1 (ICE), caspase-2 (ICH-1) or caspase-3 (CPP32). Immunoblot
      analysis revealed that caspase-3, but not caspase-1 nor caspase-2, cleaved fodrin
      to a 120 kDa fragment, wheres both caspases-1 and -3 (but not caspase-2) cleaved
      actin. We conclude that CASP gene family members participate in granulosa cell
      apoptosis during ovarian follicular atresia, and that collapse of the granulosa
      cell cytoskeleton may result from caspase-3-catalyzed fodrin proteolysis.
      However, the discrepancy in the data obtained using intact cells (actin not
      cleaved) versus the cell-free extract assays (actin cleaved) raises concern over
      previous conclusions drawn related to the role of actin cleavage in apoptosis.

PMID- 16465284
TI  - Integrin up-regulation as marker of neuroblastoma cell differentiation:
      correlation with neurite extension.
AB  - We have characterized the adhesion properties, integrin expression, and
      morphological changes due to extracellular matrix (ECM)-integrin interactions in
      a neuronal model. We showed that a modulation of some integrin heterodimers
      occurs during interferon-gamma (IFN-gamma) induced neuroblastoma (NB) cell
      differentiation. To better elucidate the possible implication and function of
      integrin receptors during neuronal maturation, we analyzed the changes in
      integrin expression in two human NB cell lines, LAN-5 and GI-LI-N, which
      represent different stages of neuronal differentiation. These models show
      opposite morphological maturation after interferon-gamma and tumor necrosis
      factor-alpha (IFN-gamma+TNF) treatment. While LAN-5 cells acquired the ability to
      extend long and branched neurites, GI-LI-N cells did not. Both cell lines showed
      enhanced expression of phenotypical and biochemical markers of neural maturation.
      Moreover, retinoic acid (RA) had different effects on the two NB cell lines: on
      LAN-5 cells it acts as a differentiation-promoting agent, while on GI-LI-N cells
      it has an antiproliferative effect, driving them to apoptosis. RT-PCR experiments
      and immunoprecipitation assays showed a late but marked increase in the
      expression of alpha1, alpha2, alpha3, and beta1 chains after IFN-gamma+TNF
      treatment of LAN-5 cells, and only alpha1 and beta1 chains upon RA induction.
      Treatment with IFN-gamma+TNF induced GI-LI-N cells to show only a late and
      remarkable increase of alpha1/beta1 heterodimer; on the contrary, RA treatment
      caused a decrease in all integrin chains. These changes are accompanied in
      differentiated cells by substantial increases in cell attachment to all purified
      ECM components tested and an increase of neurite-bearing cells and of average
      neurite length. In conclusion, these findings indicate a close correlation
      between up-regulation of integrins and neuronal morphogenesis.

PMID- 16465285
TI  - Butyrate- but not TGFbeta1-induced apoptosis of colorectal adenoma cells is
      associated with increased expression of the differentiation markers E-cadherin
      and alkaline phosphatase.
AB  - Sodium butyrate and transforming growth factor beta (TGFbeta1) are growth
      inhibitory to colonic adenoma cell lines. Butyrate induces apoptosis, whereas in
      some adenoma cell lines, TGFbeta1 can be growth inhibitory without apoptosis. In
      this report, we show that the adenoma cell line PC/BH/C1 undergoes apoptosis in
      response to TGFbeta1. Butyrate induced cell death is preceded by the induction of
      two markers of colonic differentiation--alkaline phosphatase (ALP) activity and E
      cadherin protein expression. However, TGFbeta1-induced apoptosis was not
      accompanied by induction of these differentiation markers. It is possible that
      the apoptosis induced by TGFbeta1 in the adenoma cell line PC/BH/C1 is due to
      conflicting signals, as downregulation of c-myc protein in response to TGFbeta1
      occurs only slowly in this cell line. Development of resistance to TGFbeta1 in
      colonic tumours may involve two separate stages--resistance to growth inhibition
      and resistance to TGFbeta1-induced apoptosis. Our results indicate that sodium
      butyrate induces apoptosis via differentiation, but TGFbeta1 induces apoptosis by
      a differentiation-independent mechanism. As for butyrate, the induction of E
      cadherin expression is a potentially important chemopreventative action, since
      increased E-cadherin expression has been correlated with decreased metastatic
      potential. This is the first report of induction of E-cadherin by a naturally
      occurring factor in the diet. Butyrate may reduce tumour growth and invasion, not
      only as a result of the induction of apoptosis, but also through increased
      expression of E-cadherin.

PMID- 16465286
TI  - Anti- and pro-apoptotic activities of baculovirus and Drosophila IAPs in an
      insect cell line.
AB  - The anti-apoptotic activities of two baculovirus IAPs, OpIAP and CpIAP, were
      directly compared with that of two Drosophila IAPs, DIAP1 and DIAP2, in the same
      insect cell line, SF-21 cells. Like OpIAP and CpIAP, DIAP1 inhibited actinomycin
      D-induced apoptosis and apoptosis induced by Doom. Removal of the RING finger of
      DIAP1 reduced but did not eliminate its anti-apoptotic activity. DIAP2 was unable
      to inhibit actinomycin-D induced apoptosis but was able to partially inhibit Doom
      induced apoptosis. The baculoviral BIR and RING finger regions, when separated,
      were unable to block apoptosis induced by actinomycin D or Doom. Instead, the BIR
      regions of OpIAP and CpIAP as well as the RING finger regions of CpIAP and DIAP1
      induced apoptosis. Thus, there were significant differences in the manner in
      which the different domains of the viral and cellular homologues of IAPs
      interacted with the components of the pathways regulating apoptosis in SF-21
      cells.

PMID- 16465288
TI  - Cell shrinkage and apoptosis: a role for potassium and sodium ion efflux.
AB  - In this study we have shown that redistribution of the lipid composition of the
      external and internal leaflets of the PM during apoptosis results in two main
      alterations in the cell surface, externalisation of PS, and a looser packing of
      the lipid hydrophobic head groups in the external leaflet. Significantly, neither
      of these alterations can be directly implicated in the mechanism of apoptotic
      cell shrinkage, however they do have functions in other phases of the apoptotic
      process. Progressional studies involving morphological and flow cytometric
      evaluation, and DNA gel electrophoresis revealed that apoptotic cell shrinkage is
      associated with a decrease in [Na+]i and [K+]i which occurs after visualisation
      of chromatin condensation and internucleosomal DNA fragmentation, and prior to
      apoptotic body formation. When apoptotic cultures were supplemented with
      inhibitors of the Na+, K+-ATPase pump or the Ca2+-dependent K+ channel,
      essentially all of the respective Na+ or K+ efflux during apoptosis can be
      inhibited, suggesting that essentially all of the Na+ and K+ efflux can be
      ascribed to active pumping via the Na+, K+-ATPase pump and the Ca2+-dependent K+
      channel.

PMID- 16465287
TI  - Ras-dependent apoptosis correlates with persistent activation of stress-activated
      protein kinases and induction of isoform(s) of Bcl-x.
AB  - Ras proteins are signal transducers for many cellular responses. However, it is
      not well established whether Ras-signaling also contributes to apoptosis. We have
      constructed H-RasR12-transformed Rat1 fibroblasts using tetracycline
      operator/repressor (TetO/TetR)-based conditional vectors. Rat1/TetO-RasR12 (Rat1
      Ras) cells produced high levels of H-RasR12 protein and exhibited oncogenic
      transformation. Treatment of Rat1-Ras cells with 0.1% serum triggered massive
      apoptosis. Rat1-Ras cells expressed increased basal activities of extracellular
      response kinase (ERK) and p46/p54 stress-activated protein kinase/c-Jun NH2
      terminal kinase (SAPK/JNK). Interestingly, Ras-dependent apoptosis correlated
      with further persistent activation of both p46 and p54 SAPK/JNK and concurrent
      inhibition of ERK. Differential modulation of SAPK/JNK and ERK was not detected
      in tetracycline-treated cells that did not commit apoptosis. Furthermore, two Bcl
      x related proteins of 15 kDa and 18 kDa were highly induced in apoptotic Rat1-Ras
      cells. Our results establish a direct role for Ras in apoptosis, and suggest a
      functional relationship between H-Ras, SAPK/JNK, ERK and Bcl-x in regulating
      apoptosis.

PMID- 16465289
TI  - Tumor necrosis factor-alpha induces apoptosis in rat brown adipocytes.
AB  - Accumulating evidence demonstrates that adipose tissue is a major site of tumor
      necrosis factor-alpha (TNF-alpha) gene expression, which is markedly high in
      obese animals and may contribute to obesity-linked insulin resistance. We now
      report that recombinant murine TNF-alpha triggers the apoptotic degeneration of
      brown adipocytes differentiated in culture. Moreover, noradrenaline, which has
      been described as having trophic effects on brown fat and accelerating the
      differentiation of brown adipocytes, is capable of dose-dependently preventing
      the TNF-alpha-induced apoptosis of brown fat cells. Since obesity is
      characterized by greatly increased TNF-alpha production and reduced
      catecholaminergic activity, apoptosis was studied in the brown fat of genetically
      obese animals. In situ DNA fragmentation analysis revealed a larger number of
      apoptotic cells in the brown fat of obese (fa/fa) than in that of lean (+/+)
      Zucker rats. The exposure of obese rats to low temperatures for 7 days, which
      increases the sympathetic activity of brown adipose tissue, significantly reduces
      the number of apoptotic brown adipocytes. We hypothesize that TNF-alpha may play
      a significant role in the control of brown fat homeostasis.

PMID- 16465291
TI  - Cell cycle specific induction of HL-60 cell differentiation and apoptosis by
      mycophenolic acid.
AB  - HL-60 cells undergo terminal differentiation and apoptosis in response to
      different types of sub-toxic and toxic perturbations respectively. The mechanism
      by which cells sense different amounts of perturbation to activate pathways that
      lead to the engagement of a relevant biological response is not known. The
      response of HL-60 cells to treatment with the immunosuppressant mycophenolic acid
      (MPA), a specific inhibitor of dGTP/GTP-synthesis, allowed quantitation of a
      metabolic perturbation which triggered a cellular response. 1.5 microM MPA
      induced 38% terminal differentiation to CD14 positive, early monocyte-like cells
      and 22% cell death by apoptosis, whereas 3 microM MPA induced 70% apoptosis but
      no differentiation. Despite the difference in biological outcomes, 72 h exposure
      to both 1.5 microM and 3 microM MPA caused a similar ( approximately 75%)
      depletion of total GTP levels. Cells synchronized by centrifugal elutriation were
      treated with MPA. Elutriated cells were overall less sensitive to the effects of
      MPA but 3 microM MPA induced significantly less apoptosis and more
      differentiation in an elutriation-enriched G1-population than in a population
      normally distributed in the cell cycle, suggesting that the effects of MPA in S
      phase may subsequently lead to cell death. However, analysis of apoptosis by
      using a terminal deoxynucleotidyltransferase assay and measurement of
      bromodeoxyuridine incorporation showed that apoptosis was engaged in G1. Analysis
      of the phosphorylation status of the retinoblastoma protein demonstrated that Rb
      was hypophosphorylated prior to apoptosis and that in apoptotic cells, separated
      by flow cytometry, Rb protein was absent, presumably due to proteolysis. The loss
      of Rb protein did not appear to permit transit to S-phase, and was not
      accompanied by an expression of c-Myc. Surprisingly, therefore, an antimetabolite
      inducing a loss of GTP brought about cell death by apoptosis in the G1 phase of
      the cell cycle.

PMID- 16465290
TI  - Characterization of serum adhesive proteins that block tumor necrosis factor
      mediated cell death.
AB  - Previously we have shown that TGF-beta1 protects murine L929 fibroblasts from
      TNF/ActD-mediated cell death by inducing the expression of an extracellular
      matrix TNF-resistance triggering (TRT) protein. TRT promotes TNF-resistance via
      activation of tyrosine and serine/threonine kinases in L929 cells. To examine the
      presence of TRT activity in serum (designated STRT), human sera were diluted,
      treated with or without PMSF and subjected to sequential ammonium sulfate
      precipitation (ASP). Aliquots of the ASP protein fractions were coated onto 96
      well plates, followed by thorough washing. When L929 cells were seeded and
      cultured on the wells coated with STRT proteins, these cells resisted killing by
      TNF, TNF/ActD, doxorubicin and serum deprivation, but not by anti-Fas/ActD,
      staurosporine and ActD. STRT activity was found at the 15% ASP fraction of
      untreated sera, but shifted to the 20% ASP fraction of PMSF-treated sera. Two
      likely STRT proteins of approximately 226 and 265 kDa were found in these
      fractions, compared to the corresponding nonfunctional ASP fractions.
      Functionally, STRT was inactivated by trypsin, but not by 5 M salt, various
      serine and/or cysteine protease inhibitors, and antibodies against fibronectin,
      vitronectin, C1q, histidine-rich glycoprotein, CD44, chondroitin sulfate and
      hyaluronic acid. STRT failed to alter the expression of proteins involved in
      apoptosis such as RIP, ICH-1L, BCL-X, TIAR and IkappaBalpha, and could not induce
      IkappaBalpha degradation. The induced TNF-resistance could be reversed by
      treatment of STRT-stimulated cells with testicular hyaluronidase, as well as with
      tyrosine kinase inhibitors tyrophostin, lavendustin A and AG-490 (a selective
      inhibitor of JAK2 kinase). However, the STRT function could not be blocked by the
      MEK kinase inhibitor PD98059 and the NF-kappaB inhibitors curcumin and a
      synthetic inhibitor peptide for NF-kappaB translocation. Together, our data
      suggest that tyrosine kinase activation is involved in the STRT-mediated
      resistance to TNF and TNF/ActD in L929 cells.

PMID- 16465292
TI  - Micrococcal nuclease (endonuclease) digestion causes apoptosis and mitotic
      catastrophe with interphase chromosome condensation in human Chang liver cells.
AB  - Endonuclease activation causing genomic degradation is a pervasive hallmark of
      apoptosis and a suggested precipitating or commitment step in the suicidal
      process. Directly applied endonuclease activity has produced apoptotic-like
      effects in isolated nuclei, but not yet shown as an initiating apoptogen in whole
      cells. Mechanistically genomic damage inflicted by a variety of DNA-damaging
      agents is also known to produce mitotic catastrophe condensations characterizing
      cell cycle derangement. Morphological and molecular similarities between
      apoptosis and mitotic catastrophe have been noted, but their conjoint expressions
      from directly applied endonuclease activity has also not been shown. We show here
      micrococcal nuclease (MNase) initiating apoptosis in human Chang liver cells
      which expressed both apoptotic and mitotic catastrophe condensations. Genomic
      profiling showed (a) the two stage apoptotic sequence of large (50 kb) and small
      (200 bp) fragment cleavage demonstrated by pulse field and normal gel
      electrophoresis, respectively; (b) the sub-G1 ;apoptotic peak' with shrunken
      cells from flow cytometric evaluation of PI-DNA binding and laser forward
      scattering, (c) 3' OH termini typical of apoptotic DNA fragments labelled by
      terminal deoxynucleotidyl transferase (TdT)-mediated fluorescence tagging
      especially in the shrunken cells, and (d) positive comet assay of the apoptotic
      genome. Nuclear shrinkage evaluated by confocal image analysis was consistent
      with the apoptotic response, as was Zn2+ ion sensitivity, an established
      inhibitor of apoptotic expression. Endonuclease activity per se is apoptogenetic
      and mechanistically convergent with the mitotic catastrophe pathway in the
      proliferative cycle.

PMID- 16465293
TI  - Bcr-abl translocation can occur during the induction of multidrug resistance and
      confers apoptosis resistance on myeloid leukemic cell lines.
AB  - Apoptosis was studied in parental and mdr-1 expressing U937, HL60 and K562
      myeloid leukemic cell lines using mdr unrelated inducers of apoptosis such as Ara
      C, cycloheximide, serum deprivation, ceramide, monensin and UV irradiation.
      Apoptosis was efficiently induced by all these treatments in U937 and HL60 cells
      while K562 cells exhibited an apoptosis-resistant phenotype except with UV and
      monensin. The pattern of apoptosis resistance in mdr-1 expressing U937 (U937-DR)
      and HL60 (HL60-DR100) was similar to that presented by K562. This apoptosis
      resistant phenotype of mdr cells was not overcome by concentrations of verapamil
      inhibiting the P-gp 170 pump. The acquisition of this phenotype was posterior to
      the mdr-1 expressing phenotype since a HL60-DR5 variant, selected at the
      beginning of the induction of resistance, presented a low level of mdr-1
      expression without resistance to apoptosis. The variations observed in the Fas
      (CD95) expression between sensitive and resistant cells were not sufficient to
      account for apoptosis resistance. However, a high expression in Abl antigen was
      found in all the apoptosis-resistant cells. RT-PCR and Western blot analysis
      showed that this increase in Abl antigen content was accompanied by the
      expression in U937-DR and HL60-DR100 cells of a hybrid bcr/abl mRNA and a 210 kD
      Bcr/Abl protein which was constitutive in K562. This expression was due to the
      translocation of abl and the amplification of the bcr-abl translocated gene.
      These results are in agreement with the role of Bcr/Abl tyrosine protein kinase
      as an inhibitor of apoptosis independently of the mdr-1 expression. They also
      suggest that translocation of the abl gene in the bcr region is a highly probable
      rearrangement in the mdr-1 expressing myeloid cells and that Bcr/Abl tyrosine
      kinase effect on apoptosis needs the regulation of intracellular pH and is
      inactive against UV-induced apoptosis.

PMID- 16465294
TI  - Phenotypic characteristics and tendency to apoptosis of peripheral blood
      mononuclear cells from HIV+ long term non progressors.
AB  - The aim of this study was to analyze (i) phenotype, (ii) in vitro spontaneous and
      induced apoptosis, (iii) glutathione (GSH) intracellular content and (iv)
      inhibitors of apoptosis of potential therapeutical use in peripheral blood
      mononuclear cells (PBMC) from HIV+ long term non progressors (LTNP), in
      comparison with progressors (HIV+P) and seronegative controls (HIV-). Three
      groups of subjects were studied: 15 HIV+P (patients losing >150 CD4+/year), 9
      LTNP (subjects infected by HIV for at least 7 years without clinical and
      immunological signs of progression, with a mean of 898 CD4+/microL) and 18 HIV-.
      All subjects were living in a large community for former drug addicts, and were
      matched for age and sex. We used flow cytometry for analyzing PBMC phenotype and
      apoptosis; high performance liquid chromatography for measuring intracellular GSH
      content. PBMC phenotype of LTNP shared characteristics with those of both HIV-
      and HIV+P. Indeed, LTNP showed a normal number CD4+ cells (an inclusion
      criteria), but significantly increased numbers of CD8+ lymphocytes, activated T
      cells, CD19+, CD5+ B lymphocytes and CD57+ cells, as well as a decrease in CD19+,
      CD5- B lymphocytes and CD16+ cells. In LTNP, spontaneous apoptosis was similar to
      that of HIV- and significantly lower than that of HIV+P. Adding interleukin-2 (IL
      2) or nicotinamide (NAM) significantly decreased spontaneous apoptosis in LTNP
      and HIV+P. Pokeweed mitogen-induced apoptosis was also similar in LTNP and HIV-,
      but significantly lower than that of HIV+P. In HIV+P, but also in LTNP,
      spontaneous apoptosis was inversely correlated to the absolute number and
      percentage of CD4+ cells and directly correlated to the number and percentage of
      activated T cells present in peripheral blood. GSH intracellular content was
      greatly decreased in PBMC from HIV+P and slightly, but significantly, reduced in
      LTNP. Adding 2-deoxy-D-ribose, an agent provoking apoptosis through GSH
      depletion, to quiescent PBMC resulted in similar levels of massive cell death in
      the three groups. This phenomenon was equally prevented in the three groups by N
      acetyl-cysteine but not by IL-2. A complex immunological situation seems to occur
      in LTNP. Indeed, PBMC from LTNP are characterized by a normal in vitro tendency
      to undergo apoptosis despite the presence of a strong activation of their immune
      system, unexpectedly similar to that of HIV+P. Our data suggest that NAM and IL-2
      are possible candidates for reducing spontaneous apoptosis in HIV infection.

PMID- 16465295
TI  - Autocrine proliferating B cells are susceptible to terminal differentiation and
      apoptosis.
AB  - Lymphocytes that proliferate autonomously are thought to be arrested at certain
      steps in differentiation. Here we demonstrate that autocrine proliferating B
      cells can be induced to terminal differentiation in the presence of ionomycin
      plus phorbol dibutyrate. The mature CD23high/CD38low B cell phenotype converts to
      the CD23low/CD38high plasma cell phenotype associated with increased
      immunoglobulin secretion and PC1 expression and a loss in surface immunoglobulin.
      Simultaneously, the cells arrest in proliferation and enter apoptosis at day 10.
      The cytokines IL-1alpha, IL-6, TNFalpha and TNFbeta that are required to sustain
      continuous growth are secreted in substantially increased amounts mediating entry
      into apoptosis of the proliferating cells. Decrease in IL-10 secretion sustains
      this process. Our results draw the concept that once plasmacytoid differentiation
      is initiated, the growth sustaining network of autocrine cytokines is disturbed
      in a particular fashion depriving appropriate signals to suppress the
      differentiation associated apoptotic program.

PMID- 16465296
TI  - Apoptotic T cell death in HIV/AIDS.

PMID- 16465300
TI  - Photoageing: the darker side of the sun.

PMID- 16465301
TI  - About photo-damage of human hair.
AB  - This paper reviews the current knowledge about human hair photodamage and the
      photodegradation mechanisms proposed in the literature. It is shown that there
      are still a number of questions without answer regarding this issue. For example,
      a better understanding of the hair structural changes caused by different
      radiation wavelengths is still lacking. We also find controversies about the
      effects of sun exposure on different hair types. Explanations to these questions
      are frequently sustained on the amount and type of melanin of each hair, but
      factors such as the absence of knowledge of melanin structure and of established
      methodologies to use in human hair studies make it difficult to reach a general
      agreement on these issues.

PMID- 16465302
TI  - Photodamage to the cutaneous sensory nerves: role in photoaging and
      carcinogenesis of the skin?
AB  - Chronic exposure to ultraviolet radiation (UVR) plays a significant role in aging
      and carcinogenesis of the skin. Sensory nerve fibers densely innervate all layers
      of the skin and get in close anatomical as well as functional contact with
      cellular components of the epidermis and dermis. In this review, we address the
      impact of acute and chronic UVR exposure on the cutaneous sensory nervous system
      and its mediators. We suggest that skin cell-derived nerve growth factor (NGF)
      and skin nerve-derived neuropeptides such as substance P (SP) and calcitonin gene
      related peptide (CGRP) may play a central role in intrinsic aging as well as
      extrinsic (photo-) aging of the skin. In addition, we discuss the possible role
      of these mediators in photocarcinogenesis.

PMID- 16465303
TI  - Mast cells in photodamaged skin: what is their role in skin cancer?
AB  - In this review, changes that we have observed in the prevalence of mast cells in
      human sun-exposed skin, and their potential immunoregulatory role, are discussed.
      More specifically, in a study of Australian volunteers, the prevalence of dermal
      mast cells was increased in back-of-hand skin, anecdotally the most sun-exposed
      site of the body, but not in skin from buttock, inner arm or shoulder. By
      histological analysis of back-of-hand skin, there was a significant correlation
      between dermal mast cell prevalence and elastin content suggesting increased mast
      cell prevalence with photodamage. We hypothesised that these mast cells were
      immunomodulatory upon activation by sun exposure. However, no link was found
      between dermal mast cell prevalence in hand skin and the presence of basal cell
      carcinomas. Finally, we discuss other roles for increased numbers of mast cells
      in UV-exposed photodamaged skin.

PMID- 16465304
TI  - Pathophysiology of photoaging of human skin: focus on neutrophils.
AB  - UV-induced skin damage is the result of a complex cascade of events. Many studies
      have focused on the skin effects induced by UV-B or UV-A separately. Recently a
      UV-source that emits UV-B and UV-A together in a ratio comparable to daily
      sunlight has been introduced: i.e. solar simulated radiation (SSR). By exposing
      human skin type I-III to erythematogenic doses of UV (> or =1 MED) emitted by a
      SSR source we have noticed that: (a) neutrophils are initially the main
      infiltrating cell type in the dermis and (b) these infiltrating cells are the a
      key source of in vivo enzymatically [corrected] active enzymes such as elastase,
      [corrected] matrix metallo proteinases-1 and -9 (MMPs-1 and -9). These enzymes
      are relevant to the process of photoaging, as they break down the extracellular
      matrix. Keratinocytes and fibroblasts also produce matrix degrading enzymes, but
      to a lesser extent. Our results indicate a primary role for infiltrating
      neutrophils in the initial steps of photoaging. This is further supported by the
      observation that after exposure of skin type VI to physical doses of SSR,
      equivalent to those used for skin types I-III, no neutrophils and neutrophil
      derived enzymatic activity were observed, explaining why skin type VI is
      [corrected] less susceptible to photoaging than skin types [corrected] I-III.
      Statement: Although most of the data, referred to, have been published, the
      current perspective in which they are put together is completely novel and has
      not been published elsewhere.

PMID- 16465305
TI  - Repair of mitochondrial DNA in aging and carcinogenesis.
AB  - Mitochondria are responsible for the generation of energy in the form of
      adenosine triphosphate. These organelles contain their own genetic material,
      mitochondrial (mt) DNA. This mtDNA has been hypothesized to play a role in the
      processes of aging and carcinogenesis. Initial reports have shown that there is
      no repair of cyclobutylpyrimidine dimers (CPD). More recent reports indicate
      however, that the mitochondrion contains several defence mechanisms against
      endogenous or exogenous damaging agents such as ultraviolet radiation or
      oxidative damage. The role of these defence mechanisms in the removal of
      mitochondrial DNA damage and the link to aging and carcinogenesis-associated
      processes are discussed in this review.

PMID- 16465306
TI  - Pathways involved in sunburn cell formation: deregulation in skin cancer.
AB  - The incidence of squamous cell carcinoma of the skin is rising worldwide for
      decades. Chronic exposure to sunlight is the most important environmental risk
      factor for this type of skin cancer. This is predominantly due to the DNA
      damaging effect of ultraviolet-B (UVB) in sunlight. UVB induces also sunburn
      cells, i.e. apoptotic keratinocytes, which is a crucial protective mechanism
      against the carcinogenic effects of UVB irradiation. This process is regulated by
      a wide range of molecular determinants involved in the balance between pro- and
      anti-apoptotic pathways. Growing evidence suggests that the deregulation of this
      balance by chronic UVB irradiation, contributes to the development of skin
      cancer. This review gives a brief summary of major known pathways involved in the
      regulation of keratinocyte survival and cell death upon UVB damage and discusses
      the contribution of the deregulation of these cascades to photocarcinogenesis.

PMID- 16465307
TI  - Cellular aspects of photocarcinogenesis.
AB  - Many aspects are involved in photocarcinogenesis. Historically, genetic change
      caused by UV-B-induced pyrimidine photoproducts have been paid much attention.
      Indeed they are very important factors. However, recent reports indicate the
      involvement of many other factors. First, UV-B induces not only pyrimidine
      photoproducts but also DNA lesions modified by reactive oxygen species (ROS).
      Several reports pointed out that types of mutations that are not theoretically
      caused by pyrimidine photoproducts are frequently observed in the human skin
      cancers of sun-exposed areas and UV-B-induced murine skin cancers. In addition to
      transition-type mutations at dipyrimidine sites, mutations which may be induced
      by the presence of oxidative DNA damage, are frequently observed in the ras
      oncogene and p53 tumor suppressor gene in human skin cancers of sun-exposed area
      and in UV-induced mouse skin cancers. Second, recent studies have shown that not
      only UV-B but also UV-A is involved in photocarcinogenesis based on animal
      experiments whereas UV-B has been considered mostly responsible. UV-A induces
      indirect DNA damage via ROS and lipid peroxidation. ROS have been associated not
      only with initiation, but promotion and progression in the multistage
      carcinogenesis model. Third, biological responses other than direct influence by
      UV such as inflammatory and immunological responses and oxidative modifications
      of DNA and proteins appears also responsible for carcinogenesis. Persistent
      oxidative stress in cancer may also cause activation of transcription factors and
      protooncogenes such as c-fos and c-jun as well as genetic instability. Such a
      stress may also contribute to maintain their malignant characteristics. An
      integrated model for photocarcinogenesis is proposed.

PMID- 16465308
TI  - Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets
      for skin photoprotection.
AB  - Endogenous chromophores in human skin serve as photosensitizers involved in skin
      photocarcinogenesis and photoaging. Absorption of solar photons, particularly in
      the UVA region, induces the formation of photoexcited states of skin
      photosensitizers with subsequent generation of reactive oxygen species (ROS),
      organic free radicals and other toxic photoproducts that mediate skin
      photooxidative stress. The complexity of endogenous skin photosensitizers with
      regard to molecular structure, pathways of formation, mechanisms of action, and
      the diversity of relevant skin targets has hampered progress in this area of
      photobiology and most likely contributed to an underestimation of the importance
      of endogenous sensitizers in skin photodamage. Recently, UVA-fluorophores in
      extracellular matrix proteins formed posttranslationally as a consequence of
      enzymatic maturation or spontaneous chemical damage during chronological and
      actinic aging have been identified as an abundant source of light-driven ROS
      formation in skin upstream of photooxidative cellular stress. Importantly,
      sensitized skin cell photodamage by this bystander mechanism occurs after
      photoexcitation of sensitizers contained in skin structural proteins without
      direct cellular photon absorption thereby enhancing the potency and range of
      phototoxic UVA action in deeper layers of skin. The causative role of
      photoexcited states in skin photodamage suggests that direct molecular antagonism
      of photosensitization reactions using physical quenchers of photoexcited states
      offers a novel chemopreventive opportunity for skin photoprotection.

PMID- 16465309
TI  - Lycopene-rich products and dietary photoprotection.
AB  - Plant constituents such as carotenoids and flavonoids are involved in the light
      protecting system in plants and contribute to the prevention of UV damage in
      humans. As micronutrients they are ingested with the diet and are distributed
      into light-exposed tissues where they provide systemic photoprotection. beta
      Carotene is an endogenous photoprotector, and its efficacy to prevent UV-induced
      erythema formation has been demonstrated in intervention studies. Lycopene is the
      major carotenoid of the tomato and is a very efficient singlet oxygen quencher in
      the group of carotenoids. Following ingestion of lycopene or tomato-derived
      products rich in lycopene, photoprotective effects have been demonstrated. After
      10-12 weeks of intervention a decrease in the sensitivity towards UV-induced
      erythema was observed in volunteers. Dietary carotenoids may contribute to life
      long protection against harmful UV radiation.

PMID- 16465310
TI  - Chemoprevention of photocarcinogenesis by selected dietary botanicals.
AB  - Epidemiological, clinical and laboratory studies have implicated solar
      ultraviolet (UV) radiation as a tumor initiator, tumor promoter and complete
      carcinogen, and their excessive exposure can lead to the development of various
      skin disorders including melanoma and nonmelanoma skin cancers. Sunscreens are
      useful, but their protection is not adequate to prevent the risk of UV-induced
      skin cancer. It may be because of inadequate use, incomplete spectral protection
      and toxicity. Therefore new chemopreventive methods are necessary to protect the
      skin from photodamaging effects of solar UV radiation. Chemoprevention refers to
      the use of agents that can inhibit, reverse or retard the process of skin
      carcinogenesis. In recent years, considerable interest has been focused on
      identifying naturally occurring botanicals, specifically dietary, for the
      prevention of photocarcinogenesis. A wide variety of botanicals, mostly dietary
      flavonoids or phenolic substances, have been reported to possess substantial
      anticarcinogenic and antimutagenic activities because of their antioxidant and
      antiinflammatory properties. This review summarizes chemopreventive effects of
      some selected botanicals, such as apigenin, curcumin, grape seed
      proanthocyanidins, resveratrol, silymarin, and green tea polyphenols, against
      photocarcinogenesis in in vitro and in vivo systems. Attention has also been
      focused on highlighting the mechanism of chemopreventive action of these dietary
      botanicals. We suggest that in addition to the use of these botanicals as dietary
      supplements for the protection of photocarcinogenesis, these botanicals may
      favorably supplement sunscreens protection and may provide additional
      antiphotocarcinogenic protection including the protection against other skin
      disorders caused by solar UV radiation.

PMID- 16465311
TI  - Neonatal susceptibility to UV induced cutaneous malignant melanoma in a mouse
      model.
AB  - UV irradiation has multiple effects on skin including erythema, immunosuppression
      and the induction of keratinocyte-derived skin cancers and cutaneous malignant
      melanoma (CMM). CMM which arises from damage to the melanocyte, the pigment cell
      of the skin, is associated in epidemiologic studies with sun-exposure of
      susceptible populations, especially children. Our experimental studies have
      supported the concept that the epidemiologically observed susceptibility in
      children has a biologic basis. Hepatocyte growth factor/scatter factor (HGF/SF)
      transgenic mice neonatally irradiated with UV produce melanomas which
      recapitulate human disease in histopathology and molecular pathogenesis. In this
      model, neonatal UV is necessary and sufficient for melanoma induction although an
      additional adult dose of UV radiation significantly increased melanoma
      multiplicity. One hypothesis for the susceptibility of neonatal mice to induction
      of melanoma is that neonatal skin contains a large number of immature melanocytes
      which may result in the retention of the consequences of UV damage throughout the
      lifetime of the animal. An alternate hypothesis is that the immaturity of the
      neonatal immune system results in tolerance to melanocytic antigens produced by
      UV exposure, thus permitting the subsequent outgrowth of melanoma. Here, we
      discuss the current state of knowledge about the differences between adult and
      neonatal mice in melanocytes and immune maturation as possible factors playing a
      role in the susceptibility to melanoma in UV irradiated HGF/SF transgenic mice.

PMID- 16465312
TI  - Advanced functional properties in nanoporous coordination framework materials.
AB  - Coordination framework materials display a rich array of host-guest properties
      and are notable amongst porous media for their extreme chemical versatility. This
      article highlights a number of areas where specific function has been
      incorporated into these framework host lattices.

PMID- 16465313
TI  - Pore surface engineering of microporous coordination polymers.
AB  - Pore surface control of microporous coordination polymers is of great interest
      due to the potentially exciting functionalities it presents, such as highly
      selective separation, chemisorption, and novel catalysts and sensors. A
      discussion of our unique strategy aimed at surface engineering using
      metalloligands, i.e., introduction of coordinatively unsaturated metal centers,
      is presented.

PMID- 16465314
TI  - Organometallic crystal engineering of [(1,4- and 1,3
      hydroquinone)Rh(P(OPh)3)2]BF4 by charge assisted hydrogen bonding.
AB  - The ionic complexes [(1,4- and 1,3-hydroquinone)Rh(P(OPh)3)2]BF4 form porous
      organometallic structures dictated by charge assisted hydrogen bonding.

PMID- 16465315
TI  - First enantioselective total synthesis of neocarazostatin B, determination of its
      absolute configuration and transformation into carquinostatin A.
AB  - The first enantioselective total synthesis of neocarazostatin B, the
      determination of its absolute configuration and transformation into
      carquinostatin A are described.

PMID- 16465316
TI  - Use of ionic liquids in the study of fruit ripening by high-resolution 13C NMR
      spectroscopy: 'green' solvents meet green bananas.
AB  - Banana pulps at any ripening stage can be completely dissolved in solvent systems
      based on the ionic liquid (IL) 1-n-butyl-3-methylimidazolium chloride
      ([C4mim]Cl), and variations in the carbohydrate composition of the fruit analyzed
      directly on the resulting solutions using high-resolution 13C NMR spectroscopy.

PMID- 16465317
TI  - Activity-based high-throughput profiling of metalloprotease inhibitors using
      small molecule microarrays.
AB  - We herein describe a high-throughput small molecule microarray (SMM) method that
      enables quick and cost-effective identification of potent inhibitors of
      metalloproteases in an activity-dependent manner, thereby offering a rapid means
      for inhibitor discovery and profiling.

PMID- 16465318
TI  - Novel double-cored oligosilane dendrimers--conformational dependence of the UV
      absorption spectra.
AB  - The novel double-cored oligosilane dendrimers {[Me(Me3Si)2Si-Me2Si]2SiMe-SiMe2}2
      (4) and {[Me(Me3Si)2Si-Me2Si]2SiMe}2 (5) have been shown to display unusual UV
      absorption behaviour as a function of conformation and steric interaction in the
      longest oligosilane chains.

PMID- 16465320
TI  - Regioselective functionalization of trisubstituted pyridines using a bromine
      magnesium exchange.
AB  - A tosyloxy substituent in position 2 allows a highly regioselective Br/Mg
      exchange reaction on 3,5-dibromopyridine derivatives using iso-PrMgCl.LiCl. The
      resulting functionalized pyridylmagnesium reagents react with various
      electrophiles in position 3. Acylated pyridines of this type can be readily
      converted into pyrazolo [3,4-b] pyridines.

PMID- 16465319
TI  - Boron-mediated polymerization of ylides derived from allylic arsonium salts:
      influence of the double bond substitution on the outcome.
AB  - New oligomers or polymers are prepared by polymerization of arsonium ylides in
      the presence of boron compounds.

PMID- 16465321
TI  - Synthesis-in-place of highly-conjugated oligothiophene micropatterns via photo
      activated Ullmann coupling on copper surface.
AB  - In contrast to the traditional thermally-activated Ullmann coupling, a photo
      activated Ullmann coupling for facile synthesis of oligothiophene and
      polythiophene films and micropatterns is reported.

PMID- 16465322
TI  - Electrocatalytic nitrate hydrogenation over an H+ -conducting solid polymer
      electrolyte membrane-modified cathode assembly.
AB  - Selective electrocatalytic hydrogenation of NO3- to N2 in water has successfully
      been achieved at room temperature using a membrane-electrode assembly (MEA)
      consisting of an H+ -conducting solid polymer electrolyte (Nafion-117) and a
      surface-modified Pt cathode.

PMID- 16465323
TI  - One step assembly of a nonanuclear CrIII2NiII7 bimetallic cyanide bridged
      complex.
AB  - The reaction of hexacyanochromate with connectivity 6 and a mononuclear Ni
      complex bearing a bulky tridentate macrocycle leads in one step to the formation
      of a nonanuclear Cr2Ni7 complex with central low spin and peripheral high spin Ni
      ions; fast tunnelling of the magnetization is observed at low temperature by
      micro-SQUID studies on a single crystal.

PMID- 16465324
TI  - Supramolecular hydrogels based on beta-amino acid derivatives.
AB  - Here we report on a new class of supramolecular hydrogels based on dipeptides
      that consist of beta-amino acids, which may confer proteolytic resistance to the
      hydrogels for biomedical applications.

PMID- 16465325
TI  - Is phenyl a good migrating group in the rearrangement of organoborates generated
      from sulfur ylides?
AB  - Calculations show that the unexpected low phenyl migratory aptitude observed in
      reactions of mixed alkyl-aryl boranes with benzylic sulfur ylides can be
      attributed to (1) a conformational issue, (2) the reduction of the usual
      neighbouring effect of the phenyl in the transition state by the benzylic nature
      of the migrating terminus, (3) steric hindrance suffered by the larger phenyl
      group migrating to the hindered migrating terminus and this despite (4) the
      increase in the barrier to alkyl migration by the presence of a 'non-migrating'
      phenyl on the boron atom.

PMID- 16465326
TI  - A paramagnetic Cu(I)/Cu(II)/Zn(II) coordination polymer with multiple CN-binding
      modes and its solid-state NMR characterization.
AB  - A Cu(I)/Cu(II)/Zn(II) mixed-valent [Cu(en)2][Zn(NC)4(CuCN)2] polymer, which has a
      2-D layer structure with six structurally inequivalent cyanides in four distinct
      bonding modes, has been prepared; structurally informative 13C and 15N MAS NMR
      spectra of this paramagnetic system are readily observable.

PMID- 16465327
TI  - Synthesis and crystal structure of AlH2P3O10.2H2O; a new structure-type for
      layered acid phosphates.
AB  - The crystal structure of the layered acid phosphate, AlH2P3O10.2H2O, has been
      determined and provides a new structure-type for a series of metal phosphates
      with interlamellar regions likely to be highly suited to intercalation behaviour.

PMID- 16465328
TI  - One-pot synthesis of bi-disperse FePt nanoparticles and size-selective self
      assembly into AB2, AB5, and AB13 superlattices.
AB  - By chemically modifying the nucleation burst that generates monodisperse FePt
      nanocrystals, a mixture of Pt and Fe(x)Pt(1-x) nanoparticles forms during a one
      pot reaction that includes a small amount of Cu as a catalyst; size-selective
      precipitation yields a bi-disperse population of Fe(x)Pt(1-x) nanoparticles,
      which can assemble into high-quality AB2, AB5, and AB13 superlattice structures.

PMID- 16465330
TI  - Novel butterfly pyrene-based organic semiconductors for field effect transistors.
AB  - Novel butterfly pyrene derivatives functionalized with trifluoromethylphenyl and
      thienyl aromatic groups in the 1-, 3-, 6- and 8-positions of pyrene cores and
      have been synthesized by Suzuki coupling reactions, and their crystal structures,
      optical and electrochemical properties investigated; additionally, the field
      effect transistor using as the active material exhibited a p-type performance.

PMID- 16465329
TI  - Cavitand templated catalysis of acetylcholine.
AB  - A Zn-salen-modified cavitand templates the catalytic formation of acetylcholine
      from choline and acetic anhydride.

PMID- 16465331
TI  - Remarkable electron accepting properties of the simplest benzenoid cyanocarbons:
      hexacyanobenzene, octacyanonaphthalene and decacyanoanthracene.
AB  - The optimised structures, electron affinities, and vibrational frequencies of the
      simplest benzenoid cyanocarbons, namely hexacyanobenzene C6(CN)6,
      octacyanonaphthalene C10(CN)8, and decacyanoanthracene C14(CN)10, have been
      studied using carefully calibrated density functional methods (Chem. Rev., 2002,
      102, 231-282); the predicted adiabatic electron affinities are 3.53 eV for
      C6(CN)6, 4.35 eV for C10(CN)8 and 5.02 eV for C14(CN)10, which are significantly
      larger than those of the analogous benzenoid fluorocarbons as well as
      tetracyanoethane and tetracyanoquinodimethane.

PMID- 16465332
TI  - Fluorescent sensing of maleate versus fumarate by a neutral cyclohexane based
      thiourea receptor.
AB  - A new cyclohexyl based fluorescent anion receptor, is able to recognize maleate
      versus fumarate both as their TMA salts.

PMID- 16465333
TI  - A new method for the synthesis of Z-enediones via IBX-mediated oxidative
      rearrangement of 2-alkynyl alcohol systems.
AB  - o-Iodoxybenzoic acid (IBX) was found to mediate the conversion of alpha-alkynyl
      alcohols into Z-enediones under notably mild conditions via a novel rearrangement
      mechanism (33-65% yield, 13 examples).

PMID- 16465334
TI  - Novel weak coordination to silylium ions: formation of nearly linear Si-H-Si
      bonds.
AB  - The weakly coordinating carborane anion in ion-like trialkylsilyl species
      R3Si(CHB11Cl11) can be displaced by nucleophiles as weak as ortho
      dichlorobenzene, SO2 and trialkylsilanes, the latter forming nearly linear
      hydride bridges in R3Si-H-SiR3+ cations.

PMID- 16465335
TI  - Unexpected bromination ring-opening of tetraarylporphyrins.
AB  - An unexpected, mild, efficient bromination ring-opening method has been developed
      for convenient synthesis of various novel biladienes or brominated porphyrins by
      controlling the amounts of NBS used.

PMID- 16465337
TI  - One-pot synthesis of YF3@silica core/shell nanoparticles.
AB  - A new one-pot synthetic method for preparing core/shell YF3@SiO2 nanoparticles
      with different morphologies, from spherical to elongated structures ("pearl
      necklace"), is described; absorbance and photoluminescence spectroscopy reveals
      intrinsic but no extrinsic defects in the YF3.

PMID- 16465336
TI  - Visible light-induced highly selective transformation of olefin to ketone by
      2,4,6-triphenylpyrylium cation encapsulated within zeolite Y.
AB  - 2,4,6-Triphenylpyrylium cation encapsulated within zeolite Y promotes highly
      selective transformation of olefins to ketones with molecular oxygen, under
      visible light (lambda > 400 nm) irradiation at room temperature.

PMID- 16465338
TI  - A novel photoreversible poly(ferrocenylsilane) with coumarin side group:
      synthesis, characterization, and electrochemical activities.
AB  - A novel poly(ferrocenylsilane) with a coumarin side group was synthesized. This
      photoreversible polymer exhibits interesting electrochemical activities, which
      change with photodimerization and photoscission reactions of the coumarin
      moieties.

PMID- 16465339
TI  - Multifunctional catalysis by Pd-polyoxometalate: one-step conversion of acetone
      to methyl isobutyl ketone.
AB  - Pd metal supported on Cs2.5H0.5PW12O40 is an efficient bifunctional catalyst for
      the one-step conversion of acetone to methyl isobutyl ketone in gas and liquid
      phase.

PMID- 16465340
TI  - Manipulated photocurrent generation from pigment-exchanged photosynthetic
      proteins adsorbed to nanostructured WO3-TiO2 electrodes.
AB  - A novel photoelectrode (PE) consisting of the pigment-exchanged photosynthetic
      reaction center (RC) trapped on the mesoporous WO3-TiO2 film was fabricated to
      facilitate bio-photoelectric conversion by manipulating the excitation relaxation
      of the proteins.

PMID- 16465341
TI  - Polydiphenylsilanes bearing photosensitive azocrown groups.
AB  - This work presents the synthesis and particularities of the reversible trans-cis
      UV light induced photoisomerization process of a polydiphenylsilane bearing
      (propyl-oxyphenylazo)dibenzo-18-crown-6 side groups.

PMID- 16465342
TI  - Domino-cyclisation and hydrogenation of citronellal to menthol over bifunctional
      Ni/Zr-Beta and Zr-beta/Ni-MCM-41 catalysts.
AB  - The one-pot conversion of (+/-)-citronellal to menthol can be selectively
      catalysed by either a bifunctional Ni/Zr-zeolite beta catalyst or a dual catalyst
      system of Zr-beta and Ni/MCM-41, giving a high diastereoselectivity to (+/-)
      menthol of 90-94%.

PMID- 16465343
TI  - Large scale synthesis of uniform silver@carbon rich composite (carbon and cross
      linked PVA) sub-microcables by a facile green chemistry carbonization approach.
AB  - A facile green chemistry carbonization method has been discovered for the
      synthesis of uniform silver@carbon rich composite (carbon and cross-linked
      polyvinyl alcohol) core-shell sub-microcables in large quantities, where the
      carbon sources such as glucose-based saccharides have played important roles in
      the formation of these novel sub-microcables.

PMID- 16465344
TI  - Hyperbranched polyselenides as glutathione peroxidase mimics.
AB  - Novel hyperbranched polyselenides with multi-catalytic sites at the branching
      units have been synthesized which may provide a new approach towards glutathione
      peroxidase mimics.

PMID- 16465345
TI  - Organocatalytic C3-selective Friedel-Crafts alkylations of indoles with
      alpha,beta-unsaturated ketones.
AB  - The use of an equimolar amount of pyrrolidine and HClO4 (30 mol%) was found to be
      effective in promoting the conjugate addition of indoles to (E)-alpha,beta
      unsaturated ketones, affording the corresponding beta-indolyl ketones in
      excellent yields.

PMID- 16465346
TI  - Prevention, not treatment, remains the Holy Grail for winning the war against HIV
      and AIDS.

PMID- 16465347
TI  - Improving the quality of cause-of-death statistics in South Africa--some
      practical steps.

PMID- 16465348
TI  - Could a snip in time save lives?

PMID- 16465349
TI  - Twenty years of medical education in rural South Africa--experiences of the
      University of Transkei Medical School and lessons for the future.

PMID- 16465350
TI  - Should we be initiating antiretroviral therapy earlier? An argument in favour.

PMID- 16465351
TI  - Symptomatic hyperlactataemia and lactic acidosis in the era of highly active
      antiretroviral therapy.

PMID- 16465352
TI  - Development and organisation of an instructional course on epidemic/outbreak
      preparedness and response for health workers in the Eastern Cape.

PMID- 16465353
TI  - Surrogate motherhood.

PMID- 16465354
TI  - Ehrlichia ruminantium, an emerging human pathogen--a further report.

PMID- 16465355
TI  - Ocular rhinosporidiosis.

PMID- 16465356
TI  - Glucose tolerance in rural women with pre-eclampsia.
AB  - OBJECTIVE: To determine the relationship between pre-eclampsia and glucose
      intolerance among rural women from the Transkei region of South Africa. METHODS:
      Women with confirmed pre-eclampsia underwent a 75 g, 3-hour oral glucose
      tolerance test. A control group of normotensive pregnant women were subjected to
      a similar glucose tolerance test. Pre-eclampsia was defined as blood pressure
      (BP) of at least 140/90 mmHg occurring for the first time after mid-pregnancy, in
      association with proteinuria. The control group comprised women with singleton
      pregnancy and normal BP, with age, parity and gestational age comparable to those
      of the pre-eclampsia group. RESULTS: There were 117 subjects in the pre-eclampsia
      group and 94 in the normotensive pregnancy group. Mean fasting plasma glucose
      levels in the pre-eclampsia group (3.88 +/- 0.05 mmol/l) were similar to levels
      in the normotensive group (3.97 +/- 0.05 mmol/l, p = 0.214). Peak post-load
      plasma glucose levels in the pre-eclampsia group (5.96 +/- 0.12 mmol/l) were
      similar to levels in the normotensive group (5.71 +/- 0.13 mmol/l, p = 0.180),
      and post-load incremental glucose area under the curve in the preeclampsia group
      (4.16 +/- 0.21) was similar to that in the normotensive group (3.95 +/- .21, p =
      0.495). CONCLUSION: Rural women with pre-eclampsia from the Transkei region of
      South Africa have normal glucose tolerance.

PMID- 16465357
TI  - Facilitating the integrated small-group tutorial in a medical programme--the
      University of Transkei (Unitra) experience.
AB  - CONTEXT: The Unitra (now Walter Sisulu University) medical programme is problem-
      and community-based, offered in a small-group tutorial setting under a tutor. The
      first 3 years of the programme are integrated horizontally and vertically. The
      hypothetico-deductive format, with progressive disclosure, is utilised in the
      tutorial process. Regular training of tutors is carried out to assist faculty in
      adapting to the new methods of training. Performance of tutors is regularly
      assessed by students. OBJECTIVES: To describe the students' perceptions of the
      faculty performance as tutors over the past 10 years of the problem-based
      learning/community-based education programme and to construct a profile of a
      Unitra tutor. DESIGN: A prospective longitudinal study. SETTING: The first 3
      years of the medical programme is divided into 10 blocks lasting 10 weeks each.
      At the end of each block, students evaluate their tutors using a pre-designed
      form with items pertaining to both process and content facilitation. For each
      item, the tutor is assigned a score on a scale that ranges from 'unacceptable' to
      'superlative'. Students' evaluations over the years were reviewed and the
      findings were analysed for trends and similarities. MAIN OUTCOMES: Process
      facilitation and content facilitation. RESULTS: Evaluations from 460 individual
      tutorial groups, and of 83 tutors, were analysed. PROCESS FACILITATION: Tutors
      were regular in attendance, were punctual and showed enthusiasm for the tutorial
      process. They were proficient in keeping the group on track, in giving feedback
      to the group, and in helping the group to function. They were less proficient in
      managing group time and in giving feedback to individuals within the group. They
      did not give students adequate direction in the clinical reasoning process.
      CONTENT FACILITATION: Tutors were proficient in asking probing questions, in
      encouraging students to pursue learning issues, in integrating basic and clinical
      sciences and in identifying learning errors, and they often shared their
      experiences with students. They tended to teach within the tutorial session, and
      did not lay strong emphasis on psycho-social issues raised by the cases.
      CONCLUSION: The students are generally happy with the Unitra tutors. Content is
      better facilitated than process. Integrating psychosocial issues into the
      tutorial process, minimizing teaching in the tutorial room, giving feedback to
      individuals, and giving appropriate guidance to students in the hypothetico
      deductive clinical reasoning process are the major challenges facing the Unitra
      tutor.

PMID- 16465358
TI  - Firearm fatalities in the Transkei region of South Africa, 1993-2004.
AB  - BACKGROUND: Firearms are a causative factor in much violence-related morbidity
      and mortality, including suicide. Interventions focus on stricter gun control. In
      South Africa multisectoral collaboration is needed in this regard. OBJECTIVE: To
      determine the incidence of firearm-related deaths in the Transkei region and to
      understand the underlying causative factors. METHOD: A record review was
      undertaken of 10,860 medicolegal autopsies performed between 1993 and 2004 at
      Umtata General Hospital. RESULTS: Between 1993 and 2004 10,860 autopsies were
      performed on patients who died as a result of trauma and other causes at Umtata
      General Hospital. The average number of gunshot related-deaths during this period
      was 48.4 per 100,000 of the population per year. The rate increased from
      27/100,000 in 1993 to 42/100,000 in 2004. Firearm-related deaths accounted for
      29% of all traumatic deaths, and males (82%) outnumbered females 4.6:1, although
      there is an increasing incidence among females. About 50% of these deaths were in
      the 21-40-year age group. Interpersonal violence, poverty, and use of drugs and
      alcohol were common underlying factors. CONCLUSION: There is a high incidence of
      firearm-related deaths in Transkei. Stricter gun control is required.

PMID- 16465360
TI  - Comparison of inflammatory response to polyglytone 6211 and polyglecaprone 25 in
      a rat model.

PMID- 16465359
TI  - The cost of a rapid-test VCT clinic in South Africa.
AB  - CONTEXT: Demand for HIV voluntary counselling and testing (VCT) will increase as
      HIV prevention and treatment scale up in South Africa. Understanding the cost of
      delivering VCT will inform funding decisions. OBJECTIVE: To determine the cost
      per client completing VCT (pretest counselling, testing and post-test
      counselling) in a non-research- based programme using rapid-test technology.
      DESIGN: One year of expenditure and output data were collected retrospectively as
      part of the PANCEA (Prevent AIDS: Network for Cost-Effectiveness Analysis) study.
      Market prices were determined for donated resources. SETTING: An urban, church
      based, non-profit organisation that offers rapid-test VCT services in KwaZulu
      Natal, South Africa. RESULTS: Financial expenditure for the 2002/2003 fiscal year
      was 39,761 dollars (calculated using an average conversion rate for July 2003,
      which was 0.133). Using market prices for donated resources, the economic cost
      for the year was estimated at 67,248 dollars. Six hundred and sixty-two clients
      completed VCT, resulting in financial expenditure of 60.06 dollars per client and
      an economic cost of 101.58 dollars per client. Financial expenditures and
      economic costs per client decreased over the year by 66% because expenses
      remained stable as more clients were served. CONCLUSIONS: The cost of providing
      VCT services was higher than previously reported, but declined with expanding
      scale.

PMID- 16465361
TI  - Treatment of bone metastasis induced by MDA-MB-231 breast cancer cells with an
      antibody against bone sialoprotein.
AB  - The extracellular bone matrix protein bone sialoprotein (BSP) is considered to
      play an important role in the pathogenesis of lytic skeletal lesions which are
      associated with severe morbidity in breast, prostate or lung cancer patients. In
      addition to in vitro studies, nude rats were implanted with 10(5) MDA-MB-231
      cells transfected with GFP into a small branch of the femoral artery. Osteolytic
      lesions of the respective hind leg were detected by X-ray and CT analysis as well
      as by immunohistochemistry. Exposure of MDA-MB-231GFP cells in vitro to an
      antibody against BSP (0-400 microg/ml) decreased proliferation, colony formation
      and migration of these cells by up to 95, 83 and 89 T/C%, respectively. In nude
      rats, pre-incubation of MDA-MB-231GFP cells prior to inoculation (25-100
      microg/ml) reduced the mean osteolytic lesion size to 22 T/C% after 90 days of
      observation (p<0.05). Treatment of overt lytic metastasis with the anti-BSP
      antibody (10 mg/kg) resulted in a significantly smaller mean lesion size of 57
      T/C% at the end of the observation period (p<0.05) as well as in new bone
      formation. Immunohistochemical analysis revealed the presence of BSP in MDA-MB
      231GFP cells and in vessel endothelium cells during processes such as migration
      and invasion. In conclusion, an anti-BSP antibody decreased proliferation, colony
      formation and migration of MDA-MB-231GFP cells in vitro and reduced osteolysis
      besides inducing bone formation in a nude rat model.

PMID- 16465362
TI  - Dendritoma vaccination combined with low dose interleukin-2 in metastatic
      melanoma patients induced immunological and clinical responses.
AB  - A pilot clinical trial using dendritomas, purified hybrids from the fusion of
      dendritic/tumor cells combined with a low dose of IL-2, in metastatic melanoma
      patients was conducted in order to determine its safety and potential
      immunological and clinical responses. Ten metastatic melanoma patients were
      enrolled into this study. Dendritoma vaccines were created by fusing dendritic
      cells stained with green fluorescent dye with irradiated autologous tumor cells
      stained with red fluorescent dye and purifying the hybrids using immediate
      fluorescent-activated cell sorting. Initial vaccine was given subcutaneously and
      followed by IL-2 in serially elevated doses from 3-9 million units/m2 for 5 days.
      Repeated vaccinations were administered without IL-2, at 3-month intervals for a
      maximum of 5 times. Immune reactions were measured by the increase of interferon
      gamma (IFN-gamma) expressing T cells. Vaccine doses ranged from 250,000 to
      1,000,000 dendritomas. There was no grade 2 or higher toxicity directly
      attributable to the vaccine. All patients experienced toxicity due to IL-2
      administration (9-grade 2, 3-grade 3, 1-grade 4). Eight of nine evaluable
      patients demonstrated immunologic reactions by increased IFN-gamma expressing T
      cells. One patient developed partial response at 12 weeks after the first
      vaccine. Nine months later, this patient achieved a complete response. In
      addition, two patients had stable disease for 9 and 4 months, respectively; one
      patient had a mixed response. Our findings demonstrated that dendritoma vaccines
      with a low dose of IL-2 can be safely administered to patients with metastatic
      melanoma and induce immunological and clinical responses.

PMID- 16465363
TI  - PCPH expression is an early event in the development of testicular germ cell
      tumors.
AB  - Testicular germ cell tumors (TGCTs) include various malignancies with distinct
      pathologies that share a common precursor lesion (intratubular germ cell
      neoplasia, unclassified, ITGCNU, or carcinoma in situ, CIS). TGCTs, as a whole,
      represent a highly curable tumor paradigm, with high sensitivity to radiotherapy
      and, especially, to cisplatin-based chemotherapy. However, a percentage of cases
      display therapeutic resistance, and the molecular mechanisms underlying such
      resistant phenotype remain to be elucidated. We put forward the notion that
      expression of oncogenic forms of the PCPH gene, which are known to confer
      resistance to radiation and chemotherapeutic drugs, including cisplatin, may be
      expressed in TGCTs, and thus contribute to the development of therapeutic
      resistance. To begin testing this concept, we studied PCPH expression in human
      TGCT cell lines and in 54 solid tumors by RT-PCR, western immunoblot and
      immunohistochemistry. The results demonstrated that: i) PCPH is expressed in TGCT
      cell lines and tumors, including CIS; ii) its expression levels vary among
      different TGCT pathologies, being generally higher in well differentiated regions
      and lower in areas of predominant proliferation; iii) PCPH expression is
      substantially increased in tumors relative to matched normal testicular tissue;
      iv) tumor samples express PCPH polypeptides of low molecular mass, consistent
      with the known size of the PCPH oncoprotein, that are either absent from, or
      markedly reduced in, matched normal tissue. Collectively, these results
      positively identify PCPH as a good early molecular marker for testicular
      neoplasms, and strongly indicate that immunodetection of truncated PCPH
      polypeptides may be a useful diagnostic tool for TGCT.

PMID- 16465364
TI  - Combined spectral karyotyping, comparative genomic hybridization, and in vitro
      apoptyping of a panel of Burkitt's lymphoma-derived B cell lines reveals an
      unexpected complexity of chromosomal aberrations and a recurrence of specific
      abnormalities in chemoresistant cell lines.
AB  - The comprehensive cytogenetic profiles of a panel of 10 Burkitt's lymphoma (BL)
      derived B cell lines, designated Akata, BL-28, BL-41, Daudi, DG-75, Mutu I, Mutu
      III, Namalwa, Rael, and Ramos, respectively, are reported herein. The unique
      origin of each cell line was established using multiplex quantitative
      fluorescence polymerase chain reaction (QF-PCR). Spectral karyotyping (SKY)
      revealed a large number of structural and numerical chromosomal aberrations, many
      of which had not been previously identified or resolved by conventional G-banding
      techniques. Notably, whereas all 10 cell lines harbored the hallmark
      translocation t(8;14)(q24;q32), no other common structural aberrations were
      identified, although translocations involving chromosomes 3, 13, and 17 were
      frequently seen. Moreover, analysis of chromosomal breakpoints by comparative
      genomic hybridization (CGH) revealed a number of recurring aberrations, such as
      gain of chromosomes 7 and 20, gains of regions at 2p, 3q, 13q and 16q, and losses
      at 3p, 4q and 17p. In addition, apoptyping (i.e. determination of in vitro
      responses to apoptosis stimulation) of the cell lines suggested specific
      association patterns between karyotypic changes (e.g. translocations involving
      17p, and gains of portions of chromosomes 7 and 20) and resistance to the
      chemotherapeutic agent, etoposide. The current molecular cytogenetic
      characterization of 10 BL cell lines has thus identified several novel sites of
      rearrangements; moreover, the combined karyotyping and functional assessment
      (apoptyping) of these cell lines serves to enhance their utility in future
      studies aimed at gene discovery and gene function.

PMID- 16465365
TI  - Gene expression profiles of oral leukoplakia and carcinoma: genome-wide
      comparison analysis using oligonucleotide microarray technology.
AB  - Although leukoplakia is the most common precancerous lesion of the oral cavity,
      its molecular biological properties are largely unknown. The aim of this study
      was to identify the genes responsible for its pathogenesis and malignant
      transformation using oligonucleotide microarray technology. The expression
      profiles of 8,800 genes in human oral leukoplakia (n=4) and oral squamous cell
      carcinoma (OSCC) (n=2) were analyzed using the Affymetrix GeneChip system and the
      results were confirmed with RT-PCR. Eight genes were up-regulated (>2.0-fold) and
      ten were down-regulated (<0.5-fold) in all leukoplakias analyzed with the
      GeneChip. In particular, loricrin and keratins displayed greater differences
      between normal tissue and leukoplakia. Some of the 18 alternatively expressed
      genes were markedly down-regulated in squamous cell carcinoma compared with
      leukoplakia. Our data suggested that gene abnormalities in cytoskeleton network
      components might be responsible for the development and progression of oral
      leukoplakia.

PMID- 16465366
TI  - Protein level of apolipoprotein E increased in human hepatocellular carcinoma.
AB  - Many reports suggest that hepatic steatosis leads to hepatocellular carcinoma
      (HCC), including hepatitis C virus or non-alcoholic steatohepatitis. Proteomic
      study of tumor tissues from HCC patients, focusing on apolipoprotein (apo) of
      apoA1, apoB100 and apoE, was performed by immunoblotting. Although the
      significant changes of apoA1 or apoB100 could not be shown statistically, the
      immunoblotting showed the increase in protein level of apoE in the tumor tissues
      of 88% of patients without increase of apoE gene expression and serum level.
      These results suggest the accumulation of apoE by impaired secretion. Moreover,
      immunoblot analysis on two-dimensional electrophoresis showed a strong
      possibility that sialylated forms of apoE also were increased in tumorous tissues
      of HCC. ApoE level in tumorous tissues is frequently elevated and may be a good
      histological marker for HCC.

PMID- 16465368
TI  - Resveratrol down-regulates the growth and telomerase activity of breast cancer
      cells in vitro.
AB  - A number of previous studies investigated the in vitro effects of resveratrol on
      malignant human breast epithelial cell replication. The aim of the present study
      was to evaluate the activity of resveratrol on human metastatic breast cancer
      cells. The study was performed on the MCF-7 tumor cell line. Cell growth, cell
      cycle perturbation and apoptosis were evaluated by trypan blue dye exclusion
      assay, flow cytometric analysis and confocal fluorescence microscopy. TRAP assay
      and Western blot analysis respectively detected levels of telomerase activity and
      levels of hTERT in intracellular compartments of MCF-7 cells treated with
      resveratrol. Resveratrol has a direct inhibitory effect on cell proliferation.
      The results demonstrate that the drug induces apoptosis in MCF-7 cells, in a time
      and concentration-related manner. Our results also show that the growth
      inhibitory effect of resveratrol on malignant cells is mainly due to its ability
      to induce S-phase arrest and apoptosis in association with reduced levels of
      telomerase activity. In particular, TRAP assay and Western blot analysis
      respectively showed that resveratrol treatment down-regulates the telomerase
      activity of target cells and the nuclear levels of hTERT, the reverse
      transcriptase subunit of the telomerase complex. In our experimental model of
      breast cancer, resveratrol shows direct antiproliferative and pro-apoptotic
      effects. Studies on telomerase function and intracellular hTERT distribution
      point out that this agent is endowed with additional suppressive functions on
      critical tumor biological properties. These results speak in favor of a potential
      role of resveratrol in chemoprevention/chemotherapy of breast cancer.

PMID- 16465367
TI  - Down-regulation of uPAR and cathepsin B retards cofilin dephosphorylation.
AB  - Cathepsin B and uPAR play key roles in cancer cell migration and invasion. Here,
      we demonstrate that the simultaneous, siRNA-mediated down-regulation of uPAR and
      cathepsin B inhibits glioma cell migration and is accompanied by cytoskeletal
      condensation. We show that the dephosphorylation of cofilin is inhibited by the
      down-regulation of uPAR alone and, to a lesser extent, by the down-regulation of
      cathepsin B alone, and that the effect was much higher with the down-regulation
      of both molecules by pUC. Using FACS analysis and western blotting for the
      alphaVbeta3 integrin heterodimer, we determined that down-regulating uPAR
      subsequently causes the down-regulation of the alphaVbeta3 integrin heterodimer.
      As evidenced by western blot analysis of ERK1/2, pERK1/2, p38MAPK, p-p38MAPK,
      AKT, pAKT and PI3-k, the MEK and PI3-k pathways are inhibited. From cytoskeleton
      studies, we observed that the down-regulation of uPAR caused cytoskeletal
      condensation and that the simultaneous down-regulation of uPAR and cathepsin B
      was even more effective at inducing cytoskeletal condensation than uPAR alone.
      Our results demonstrate the relevance of uPAR in cytoskeletal dynamics and the
      potential of uPAR and cathepsin B as targets in the treatment of malignant
      gliomas.

PMID- 16465369
TI  - Growth inhibitory effect of triple anti-tumor gene transfer using Semliki Forest
      virus vector in glioblastoma cells.
AB  - The gene delivery of multiple tumor suppressors can provide an efficient tumor
      therapy in the case of malignant human glioblastomas containing multiple genetic
      alteration and inactivation. As such, the current study presents a new delivery
      system that can simultaneously express three anti-tumor genes using a Semliki
      Forest virus (SFV) vector in the expectation of combined or synergistic effects
      of angiogenesis inhibition by angiostatin and apoptosis induction by p53, PTEN
      and the rSFV particle itself. Recombinant SFV (rSFV) containing three anti-tumor
      genes (rSFV-Agt/p53/PTEN) were found to efficiently transduce and express each
      anti-tumor gene in glioblastoma cells. In addition, rSFV-Agt/p53/PTEN also
      resulted in a more effective induction of apoptosis in vitro and inhibition of
      tumor growth in nude mice when compared with other rSFVs containing only one or
      two anti-tumor genes. Accordingly, the current results demonstrate that a triple
      anti-tumor gene transfer using an rSFV vector would be a powerful strategy for
      regional cancer gene therapy.

PMID- 16465370
TI  - The impact of aggregation on the biodistribution of hypericin.
AB  - Hypericin is a potent agent in the photodynamic therapy of cancers and
      accumulates to a large extent in tumor tissue. To better understand the impact of
      hypericin aggregates present in the delivery vehicle on the biodistribution of
      the compound, we compared the in vivo tissue accumulation after administering
      hypericin suspended as coarse aggregates in phosphate-buffered saline, with the
      biodistribution found after injection of a solution of hypericin in a mixture of
      DMSO, polyethylene glycol and water. When administered as coarse aggregates,
      hypericin showed a pronounced uptake in liver, spleen and lung and a slow body
      clearance with a complete decline in tumor/normal tissue ratios (far less than
      1). In contrast, delivery of hypericin as a solution resulted in dramatically
      improved tumor to normal tissue ratios and a relatively fast elimination from the
      body. To elucidate the exact localization of hypericin in both conditions, a
      fluorescence microscopy study was performed on sections of spleen, liver, lung
      and tumor tissue. At 24 h after injection, fluorescence in spleen, liver and lung
      was faint and homogeneous for dissolved hypericin, whereas bright fluorescent
      spots covering the entire tissue sections were found when coarse aggregates were
      injected. We found that aggregates get trapped within these tissues, followed by
      a gradual monomerization. A direct involvement of monocytes and macrophages,
      however, could not be demonstrated. In conclusion, it is of critical importance
      that the delivery vehicle prevents extensive aggregation of hypericin before
      injection and assures an efficient transfer to serum lipoproteins upon injection.
      These results may also be extended to radiolabeled derivatives and other
      lipophilic photosensitizers, such as porphyrins, phthalocyanines,
      naphthalocyanines and chlorines, with similar aggregation properties.

PMID- 16465371
TI  - Bcl-xL and bcl-2 proteins in melanoma progression and UVB-induced apoptosis.
AB  - Whether bcl-xL and bcl-2 play an essential role in melanoma progression and UVB
      induced apoptosis is not completely understood. We investigated the expression of
      bcl-xL and bcl-2 in matched primary and metastatic melanoma tumors and melanoma
      cell lines from the same melanoma patients to clarify the importance of bcl-xL
      and bcl-2 in melanoma progression and in UVB-induced apoptosis. The expression of
      bcl-xL and bcl-2 proteins was examined by immunohisto(cyto)chemistry and Western
      blot in melanoma tumors and melanoma cells. Cellular viability and apoptosis were
      estimated after the melanoma cells were exposed to 30, 60 and 180 mJ/cm2 UVB.
      Both primary melanoma tumors and melanoma cells showed lower expression of bcl-xL
      and bcl-2 proteins estimated as frequency of positive cells than their matched
      metastatic tumors and cells in vitro. After exposure to UVB, the cell viability
      decreased and the number of apoptotic cells increased in both primary and
      metastatic melanoma cell lines. These changes were more pronounced in the primary
      melanoma cells than in the matched metastatic cells. After UVB exposure, the
      expression of bcl-xL protein decreased in primary melanoma cells in a dose- and
      time-dependent manner, but the expression of bcl-2 was not influenced. The
      expression of bcl-xL and bcl-2 proteins was increased during melanoma progression
      from primary to metastatic melanoma. Reduction of bcl-xL, but not bcl-2
      expression was involved in UVB-induced apoptosis in primary melanoma cells.

PMID- 16465372
TI  - Allelic imbalance at 11q23-q24 chromosome associated with estrogen and radiation
      induced breast cancer progression.
AB  - Multiple genetic alterations are common in cancers including those of the breast.
      The mechanisms leading to these alterations such as point mutations, gene
      amplifications, deletions and replication error are often associated with
      frequent and consistent loss of heterozygosity (LOH) or microsatellite
      instability (MSI). Several cytological and molecular studies have shown high
      frequency loss of genetic information on the long arm of chromosome 11 (i.e.,
      11q) in various primary breast cancers. In the present study allelic alterations
      in a refined position on the long arm of chromosome 11 were studied to identify
      the spectrum of induced damage at different stages of malignant transformation of
      MCF-10F cell lines after exposure to high-LET radiation using alpha-particles and
      exposure to estradiol by using PCR-single strand conformation polymorphism (SSCP)
      and fluorescence in situ hybridization (FISH) analysis. Microsatellite markers
      were selected from chromosome 11 (11q23-q24 loci) and it was found that frequency
      of allelic imbalance occurs at different stages of tumor progression with a range
      of 15-45% depending on the marker studied. These results strongly suggested the
      presence of several tumor suppressor genes in this critical region of chromosome
      11 (11q23-q24). It also represents the first indication of allele loss at these
      loci in human breast epithelial cells induced by radiation and estrogen treatment
      suggesting a potential interventional target in breast carcinogenesis.

PMID- 16465373
TI  - Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting
      strategy.
AB  - Calicheamicin is a potent chemotherapeutic with a low therapeutic index that
      requires targeting to tumor cells for its use in the clinic. To treat acute
      myeloid leukemia, calicheamicin has been conjugated to an antibody that
      recognizes CD33 (gemtuzumab ozogamicin). The application range of this 'active'
      targeting strategy is limited since it depends on specific antigen expression by
      tumor cells. This limitation could be reduced by using an antigen-independent
      'passive targeting' strategy for calicheamicin. 'Passive targeting' relies on the
      dysfunctional vasculature of a neoplastic tumor that allows enhanced retention of
      macromolecules. We studied the efficacy of calicheamicin conjugated to various
      carrier molecules: i.e. immunoglobulin, albumin or PEGylated Fc fragments. In
      nude mice, a conjugate of anti-CD33 and calicheamicin accumulates in human tumor
      xenografts in the absence of detectable amounts of targeting antigen. Passive
      targeting provided sufficient accumulation of this conjugate to inhibit tumor
      growth of 10 different CD33-negative xenograft models. This efficacy depended on
      the use of an acid-labile linker between antibody and calicheamicin. Substitution
      of immunoglobulin as a carrier with either albumin or PEGylated Fc reduced or
      eliminated the efficacy of the conjugate. The results showed that using 'non
      specific' immunoglobulin for passive targeting of calicheamicin might be an
      effective mode of cancer therapy.

PMID- 16465374
TI  - Protein kinase CK2 subunits are positive regulators of AKT kinase.
AB  - Protein kinase CK2 is a highly conserved serine/threonine kinase ubiquitously
      distributed in all investigated eukaryotes and involved in several intracellular
      pathways which control, among others, cell cycle, proliferation, apoptosis and
      transformation. Similarly, the PI3K-AKT pathway deregulation has been shown to
      play an important role in tumor development and tumor response to anti-cancer
      treatment. In this study, it is shown that the specific inhibition of the PI3K
      AKT signaling pathway in combination with depletion of CK2 subunits by antisense
      oligodeoxynucleotides leads to an enhanced drug-induced apoptotic response.
      Moreover, in vitro as well as in vivo studies show that the individual CK2
      subunits interact with AKT kinase and that the complex formation is not modulated
      by the phosphorylation status of AKT. Furthermore, the fact that the interaction
      between CK2 subunits and AKT enhances AKT kinase activity identifies a novel
      molecular mechanism that leads to modulation of AKT activation raising the
      possibility that CK2 and AKT might be implicated in common pathways that control
      cell proliferation and survival.

PMID- 16465375
TI  - Inhibition of NF-kappaB activation and chemokine expression by the leukocyte
      glycoprotein, CD43, in colon cancer cells.
AB  - CD43 is a heavily O-glycosylated type I trans-membrane protein, expressed at high
      levels on the surface of leukocytes. It is frequently overexpressed in early
      colon adenomas, but not in normal colon epithelial cells. To identify CD43 target
      genes, gene array analysis was performed using a tetracycline-inducible CD43
      expression system in human colon adenocarcinoma SW480 cells. CD43 was
      demonstrated to down-regulate a variety of chemokine genes. Overexpression of
      CD43 suppressed constitutive as well as PMA-induced NF-kappaB activation and
      reduced the DNA binding of transcription factor p65 but not p50. Furthermore, a
      reduced NF-kappaB responsive promoter activity was observed and a decreased
      expression of proinflammatory chemokines MCP-1, IL-8 and GRO-alpha. These results
      suggest that overexpression of CD43 suppresses a subset of NF-kappaB target
      genes, partly via the inhibition of p65 transcriptional activity.

PMID- 16465377
TI  - In vitro RNA interference against beta-catenin inhibits the proliferation of
      pediatric hepatic tumors.
AB  - Mutations of beta-catenin have been identified in the majority of pediatric
      hepatic malignancies, including hepatoblastoma (HB) and hepatocellular carcinoma
      (HCC), suggesting its important contribution in hepatic tumorigenesis in this age
      group. However, the role of beta-catenin/canonical Wnt signaling pathway in the
      neoplastic growth of cancer cells has not been directly studied. To address beta
      catenin's capability in maintaining the malignant phenotype in established
      pediatric HB and HCC cell lines, HuH-6 and HepG2, harboring mutated and
      overexpressed beta-catenin, we carried out a series of in vitro analyses through
      a transfection of short interfering RNAs (siRNAs) to generate a loss-of-function
      model. HuH-7, another HB cell line derived from a pediatric patient without a
      stabilizing mutation was used for comparison. RNA interference successfully
      manipulated the degradation of overexpressed beta-catenin. In all cell lines,
      beta-catenin mRNA was suppressed by 80-90% after 48 h of transfection, and a
      reduction of its protein expression was demonstrated. In HuH-6 and HepG2, the pre
      existing beta-catenin nuclear accumulation disappeared and reductions of beta
      catenin downstream target genes, c-myc and cyclinD1, were also evidenced after
      the treatment. The in vitro proliferation of both cell lines was transiently
      inhibited. In contrast, the suppression of beta-catenin in HuH-7 did not lead to
      a significant change in the expression of target genes or cellular proliferation.
      Our data indicate that beta-catenin can be considered a specific target for gene
      therapy in pediatric hepatic tumors with mutations and overexpression of this
      gene.

PMID- 16465376
TI  - Differential gene expression profiles of radioresistant pancreatic cancer cell
      lines established by fractionated irradiation.
AB  - Identification of the genes that are differentially-expressed between
      radiosensitive and radioresistant cancer cells is important to the ability to
      predict the clinical effectiveness of radiotherapy. We established radioresistant
      human pancreatic cancer cell lines using fractionated irradiation in order to
      identify genes that are differentially-expressed between parental lines and
      radioresistant cell sublines. Six pancreatic cancer cell lines (PK-1, PK-8, PK-9,
      T3M4, MiaPaCa2 and PANC-1) were treated with 10 Gy fractionated irradiation at
      approximately two-week intervals (total dose 150-180 Gy). Five radioresistant
      sublines (PK-1, PK-8, PK-9, T3M4, and MiaPaCa2) were successfully established.
      Using oligonucleotide microarrays containing 17,086 genes, we identified 73 up
      regulated genes and 55 down-regulated genes common to radioresistant sublines.
      Subsequent analysis by quantitative RT-PCR confirmed the reliability of our
      microarray strategy. Up-regulated genes were associated with growth factor
      (example, amphiregulin), cell-cycle check point (MAPKAPK2), intracellular
      signaling pathway (regucalcin), and angiogenesis stimulation (angiopoietin 2).
      Down-regulated genes were associated with apoptosis (caspase 8), retinoid
      esterification (lecithin retinol acyltransferase), and electron transport
      (calcium-activated chloride channel 1). Some of these genes have known
      association with response to radiation, such as caspase 8 and MAPKAPK2, but
      others are novel. Global gene analysis of radioresistant sublines may provide new
      insights into the mechanisms underlying clinical radioresistance and to improving
      the efficacy of radiotherapy for pancreatic cancer.

PMID- 16465378
TI  - Insulin-like growth factor-I promotes migration in human androgen-independent
      prostate cancer cells via the alphavbeta3 integrin and PI3-K/Akt signaling.
AB  - In its phase of androgen-independence, prostate carcinoma is characterized by a
      high proliferation rate and by a strong ability to give rise to metastases. IGF-I
      has been shown to exert a potent mitogenic action on prostate cancer. We
      investigated whether IGF-I might also affect the motility of prostate cancer
      cells and defined the mechanism of action. We found that IGF-I promotes the
      migratory capacity of androgen-independent prostate cancer cells through the
      activation of its specific receptor, IGF-IR. This effect was accompanied by a
      change in cell morphology (as revealed by scanning electron microscopy), and by a
      rearrangement of the actin cytoskeleton. The treatment of cells with the PI3-K
      inhibitor, LY294002, counteracted the pro-migratory activity of IGF-I.
      Experiments were then performed to clarify whether the integrin, alphavbeta3,
      could be involved in the action of IGF-I. We demonstrated that: a) the IGF-I
      induced migration of cells is completely antagonized by an antibody specifically
      blocking the function of alphavbeta3; b) IGF-I increases alphavbeta3
      immunofluorescence at the level of cell membranes, and this effect is
      counteracted by LY294002; and c) IGF-I increases alphavbeta3 protein levels. Our
      results demonstrate that IGF-I promotes the motility of androgen-independent
      prostate cancer cells by modulating alphavbeta3 integrin activation/expression;
      these effects are mediated by the PI3-K/Akt signaling pathway. This study: a)
      supports a crucial role for IGF-I in the progression of the pathology towards the
      highly metastatic phase; and b) provides an additional rationale basis for the
      development of therapeutic strategies directed at the IGF-I/IGF-IR system in the
      treatment of androgen-independent prostate cancer.

PMID- 16465379
TI  - Native anti-tumor responses elicited by immunization with a low dose of
      unmodified live tumor cells.
AB  - The present study demonstrates that immunization with a low dose of unmodified
      live myeloma tumor cells (FO) elicited tumor-specific immunity. BALB/c mice were
      vaccinated with 10(4) live dendritic cells (DC)-FO fusion cells or 10(3) live FO
      cells. 80% of vaccinated mice survived from the later challenge with 1 x 10(6) FO
      cells, whereas all control mice developed tumors. Additionally, vaccination with
      live FO cells gave no protection against the growth of Lewis lung carcinoma cells
      in C57BL/6 mice. Cellular immunity was found to be primarily responsible for anti
      tumor responses. In an adoptive immune model, the development of myeloma was
      greatly reduced by transfusion of lymphocytes but not sera from mice immunized
      with FO. T cells from immunized mice also induced lysis of FO cells in the
      cytotoxic T lymphocyte (CTL) assay. After co-culture with FO, IFN-gamma released
      from immunized T helper cells increased >10-fold, while IL-4 remained unchanged
      in comparison with control T cells. These findings provided the first evidence
      that immunization with a low dose of unmodified live FO cells was safe to mice
      and capable of eliciting specific protective immunity against tumor growth.

PMID- 16465380
TI  - Obesity, adipokines, and prostate cancer (review).
AB  - Prostate cancer, the third most common cancer in men worldwide, varies
      substantially according to geographic region and race/ethnicity. Obesity and
      associated endocrine variation are foremost among the risk factors that may
      underlie these regional and ethnic differences. The association between obesity
      and prostate cancer incidence is complex and has yielded inconsistent results.
      Studies that have linked obesity with prostate cancer mortality, advanced stage
      disease, and higher grade Gleason score, however, have produced more consistent
      findings, indicating that obesity may not necessarily increase the risk of
      prostate cancer, but may promote it once established. Additionally, metabolic
      syndrome, which includes disturbed glucose metabolism and insulin bioactivity,
      may also be associated with prostate carcinogenesis. Adipokines, defined as
      biologically active polypeptides produced by adipose tissue, have been linked
      with a number of carcinogenic mechanisms, including angiogenesis, cell
      proliferation, metastasis, and alterations in sex-steroid hormone levels. A
      number of emerging studies have implicated the role of adipokines in prostate
      carcinogenesis. This review explores the specific roles of several adipokines as
      putative mediating factors between obesity and prostate cancer with particular
      attention to leptin, interleukin-6 (IL-6), heparin-binding epidermal growth
      factor-like growth factor (HB-EGF), vascular endothelial growth factor (VEGF) and
      adiponectin.

PMID- 16465381
TI  - Selection of non-P-glycoprotein mediated high-level etoposide resistant cell
      lines by adriamycin with P-gp inhibitors.
AB  - In murine erythroleukemia (MEL) A20 cells (grown in 20 ng/ml adriamycin),
      mutation(s) producing 10-fold adriamycin (doxorubicin) resistance emerged via an
      unknown mechanism. Exposure of A20 cells to further stepwise increasing
      concentrations of ADR in combination with MDR modulators (PSC833 and verapamil)
      aimed to amplify the undetermined A20 mechanism while controlling P-glycoprotein
      (P-gp) overexpression. The growth of the derived cell lines A30P, A40P and A60P
      (grown in 30, 40 and 60 ng/ml ADR with PSC833 and verapamil) was initially slow,
      but eventually reached near WT rates. The new cell lines A30P and A40P were only
      1.3- and 1.6-fold more resistant to adriamycin than PC4 A20. Resistance to
      vincristine was unchanged, but resistance to etoposide (VP-16) was 3.7-fold
      higher in A40P than A20 (itself 97-fold higher than wild-type). Expression of
      mdr3 and mrp mRNA tested by RT-PCR showed no increase. Daunorubicin and etoposide
      accumulation was not different among the cell lines, and no changes were detected
      in the number of daunorubicin fluorescent lysosomes. In comparison to WT, reduced
      topoisomerase IIalpha (EC 5.99.1.3) activity (20%) and protein expression (80%)
      was similar to the parental A20 cells. No mutations in the coding sequence of
      topoisomerase IIalpha could be located to account for the high etoposide
      resistance levels. The inhibitor combination of verapamil and PSC833 prevented
      the emergence of transporter mediated MDR, but not ADR selection of cell lines
      highly resistant to etoposide.

PMID- 16465382
TI  - Histone deacetylase inhibitors induce cell death and enhance the susceptibility
      to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells.
AB  - Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic
      agents with the ability to induce apoptosis and growth arrest of cancer cells. In
      addition, HDIs have been suggested to enhance the anticancer efficacy of other
      therapeutic regimens, such as ionizing radiation (IR) or chemotherapy. The
      objective of this study was to evaluate the activity of HDIs against
      medulloblastoma cells when applied either as single agents or in combination with
      IR, cytostatics, or TRAIL. The HDIs, suberoyl anilide hydroxamic acid (SAHA),
      sodium butyrate, and trichostatin A, were examined for their effects on the
      medulloblastoma cell lines, DAOY and UW228-2. We found that treatment with HDIs
      induced the dissipation of mitochondrial membrane potential, activation of
      caspase-9 and -3 and, consequently, apoptotic cell death. Moreover, all three
      HDIs significantly enhanced the cytotoxic effects of IR in DAOY cells. Likewise,
      treatment with SAHA markedly augmented the cytotoxicity of etoposide, while it
      had no effect on vincristine-mediated cell death. HDIs also potently increased
      the killing efficiency of TRAIL. TRAIL-induced, but not SAHA-induced, cell
      killing could be prevented by the caspase-8 inhibitor, z-IEDT-fmk. We conclude
      that HDIs may be useful for the treatment of medulloblastoma as monotherapy and
      particularly when given in combination with IR, appropriate cytostatics, or
      TRAIL.

PMID- 16465383
TI  - Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour
      suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma.
AB  - 3p21 is an important locus harbouring critical tumour suppressor genes (TSG),
      which are implicated in the pathogenesis of multiple tumours, including
      oesophageal carcinoma. RASSF1A is a 3p21.3 candidate TSG frequently inactivated
      by promoter methylation in multiple tumours. We investigated RASSF1A promoter
      methylation and gene expression in Chinese oesophageal squamous cell carcinoma
      (ESCC) to compare it to data from Japanese patients. Methylation-specific PCR
      (MSP) showed that RASSF1A was partially methylated in 3/7 (43%) cell lines; 22/64
      (34%) primary tumours and 3/64 (5%) corresponding non-tumour samples; and was not
      methylated in 2 immortalized normal oesophageal epithelial cell lines and 6
      normal oesophageal epithelium samples. Bisulfite genome sequencing confirmed the
      MSP results. Promoter hypermethylation correlated well with RASSF1A mRNA down
      regulation. Treatment of cell lines with 5-aza-2'-deoxycytidine activated RASSF1A
      mRNA expression along with promoter demethylation. RASSF1A hypermethylation in
      the Chinese cohort was much lower than in a published report of Japanese ESCC
      patients (52%) and cell lines (74%). Our own analysis of Japanese ESCC cell lines
      for direct comparison also detected a high frequency of RASSF1A hypermethylation
      (8/10; 80%) and high levels of hypermethylation at each CpG site. No significant
      association between RASSF1A hypermethylation and histological differentiation
      (p=0.953), tumour staging (p=0.117), or survival (p=0.7571) was found in Chinese
      ESCC, unlike the results of Japanese patients. The incidence of oesophageal
      cancer shows marked variation by geographic area and ethnic group; it is almost
      three times higher in China than in Japan, indicating possible different
      pathogenetic mechanisms. Our results show that RASSF1A hypermethylation in ESCC
      has epidemiological/ethnic differences, and suggest that Chinese ESCC may result
      from different pathogenetic mechanisms.

PMID- 16465384
TI  - Enhancing the photodynamic effect of hypericin in human bladder transitional cell
      carcinoma spheroids by the use of the oxygen carrier, perfluorodecalin.
AB  - In the present study, we evaluated the possibility of enhancing the photodynamic
      effect of hypericin in transitional cell carcinoma (TCC) spheroids by the use of
      the oxygen carrier, perfluorodecalin. Following incubation with hypericin, RT-112
      TCC spheroids were irradiated in the presence or absence of perfluorodecalin, at
      light doses of 7 J/cm(2) or 28 J/cm(2) , delivered at a fluence rate of 15
      mW/cm(2) . The photodynamic therapy (PDT) efficacy was evaluated and apoptotic
      cells were visualized. The results show that, in the absence of perfluorodecalin,
      spheroidal TCC cells are inadequately sensitive to hypericin PDT. As was shown by
      fluorescence microscopy, this lack of activity was not due to insufficient
      photoactive concentrations of hypericin reaching the inner parts of the
      spheroids. Conversely, enhanced oxygenation of spheroids by perfluorodecalin led
      to a dramatic enhancement of hypericin PDT efficacy. The detection of nuclear
      shrinkage or fragmentation with DAPI staining and the assessment of cell
      morphology by light microscopy indicated that apoptosis was the most prominent
      response of spheroids to hypericin PDT in the presence of perfluorodecalin. In
      conclusion, the results of this study suggest that perfluorocarbons, such as
      perfluorodecalin, are useful in enhancing the oxygenation of tumor tissue,
      resulting in highly efficient hypericin PDT. Since hypericin becomes concentrated
      specifically in human bladder urothelial carcinoma lesions and the bladder is
      very well suited to instillation with a perfluorocarbon, combining the techniques
      looks very promising for an efficient and selective whole bladder wall
      photodynamic antitumoral treatment in a urological clinical setting.

PMID- 16465386
TI  - Tightly regulated distribution of family members of proteins is related to social
      property in the open body system (Review).
AB  - Environmentally mediated systemic involvement of autoimmunity, allergy and
      carcinogenesis are very common by clinical and epidemiological investigation.
      However, there is an unknown relationship between environment and environmentally
      mediated systemic involvement of autoimmunity, allergy and carcinogenesis. This
      unknown molecular communication or response conducts the primary injury sites of
      the skin, and surface mucosa in the respiratory, alimentary, or reproductive
      tracts, to the secondary sites or even the whole body under some physiological
      and pathological conditions. Also, this unknown molecular communication or
      response involves a variety of molecular events, detectable in systemic
      differentiation, overexpression, hyperplasia, carcinogenesis, allergies or
      autoimmunity. The family members of proteins and their relatives are almost
      ubiquitous, and distribution is tightly regulated at all three administrative
      levels to form an interacting multiprotein complex. The key question is whether
      there is unknown communication or response among the family members and, if there
      is, is it associated with some social property of the proteins in the open body
      system?

PMID- 16465385
TI  - Combination gene therapy with p53 and Thoc1/p84 is more effective than either
      single agent in an animal model of human pancreatic adenocarcinoma.
AB  - Gene therapy utilizing tumor suppressor gene p53 has been tested in a number of
      cancers in both preclinical models and clinical trials. Despite the ability of
      p53 to significantly inhibit tumor growth in preclinical models, it has met with
      more limited clinical success. This is due, in part, to the observation that a
      substantial fraction of tumors are resistant to the effects of p53 expression. We
      have tested whether combination therapy with Thoc1/p84 and p53 is more effective
      than single gene therapy in a p53-resistant tumor model of human pancreatic
      adenocarcinoma. Infection with Thoc1/p84 and p53 adenovirus inhibits pancreatic
      cancer cell growth in vitro and in vivo to a greater extent than treatment with
      either one alone at the same total viral dose. Similar results are observed with
      Thoc1/p84 and Rb1 gene therapy. The data support the use of therapy that targets
      both the p53 and Thoc1/p84 pathways in tumors that are resistant to perturbation
      of the p53 pathway alone.

PMID- 16465387
TI  - Interaction between heat shock protein 70 kDa and calcineurin in cardiovascular
      systems (Review).
AB  - Cells have the capability of defending themselves from various stressors by
      activating a genetic program with the production of substances known as heat
      shock proteins (Hsps) and their regulatory partners, the heat shock transcription
      factors. Hsps play a major role in systemic hypertension, coronary artery
      disease, carotid atherosclerosis, myocardial infarction and myocardial ischemia.
      In this review we discuss the interaction between Hsp70 and CaN which was carried
      out in our laboratory. We demonstrated that the cardiac Hsp70 stimulated a 2-fold
      increase in calcineurin (CaN) activity. In addition, the pull-down assay revealed
      that Hsp70 directly interacts with CaN. Furthermore, expressed cardiac specific
      Hsp70 was phosphorylated in vitro by cAMP-dependent protein kinase. The
      phosphorylated Hsp70 was unable to activate the phosphatase activity of CaN. For
      the first time we demonstrated that Hsp70 is phosphorylated by cAMP-dependent
      protein kinase and provides an on/off switch for the regulation of CaN signaling
      by Hsp70. This will lead to therapeutic benefit in human diseases such as
      atherosclerosis, cardiomyopathy, congestive heart failure, and ischemia.

PMID- 16465388
TI  - Molecular characterization of the zinc finger transcription factor, Osterix.
AB  - Osterix was identified as a transcription factor expressing, in osteoblasts,
      required for bone formation. However, the molecular mechanisms of the gene
      regulation by Osterix remain elusive. In this study, we examined the
      transactivation property of Osterix by using the Gal4 fusion system reporter
      assay. We identified the transactivation domain of Osterix, which contains high
      proline and glycine residues and has an activation property in mammalian and
      yeast cells. The GST-pull down analysis revealed that the basal transcription
      factor, TF-IIB, but not TBP, binds to the transactivation domain. Furthermore, we
      found that Osterix interacts with chromatin remodeling factor, Brg-1, through its
      C-terminal zinc finger domain in vivo and in vitro. These findings suggest that
      Osterix possesses functional domains which associate with transcription mediated
      factors and functions as a transcriptional activator in the nucleus.

PMID- 16465389
TI  - Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of
      beta-amyloid on rat brain microvascular endothelial cells.
AB  - Several studies have demonstrated that cerebrovascular dysfunction and damage
      play a significant role in the pathogenesis of Alzheimer disease (AD). In fact,
      beta-amyloid peptides (Abetas), the major component of the senile plaques and
      cerebrovascular amyloid deposits in AD, were shown to be cytotoxic to endothelial
      cells. We have recently observed that Abetas exert a toxic effect on
      neuromicrovascular endothelial cells (NECs) in a time- and concentration
      dependent manner, apoptosis playing a pivotal role in this process. Hence, it
      seemed worthwhile to investigate the Abeta-mediated apoptosis mechanism in NECs.
      Abetas were found to induce, after a short incubation period, apoptosis
      throughout caspase-8 activation. Moreover, Abetas elicited a highly significant
      (p < 0.001) increase in superoxide dismutase (SOD) levels after a 3-h exposure
      period, while SOD concentration was not affected after a 24-h incubation. The
      time-dependent increase in SOD concentration is probably correlated with the
      production of an excess of reactive oxygen species. Collectively, our findings
      allow us to conclude that: i) Abetas may induce apoptosis via the activation of
      caspase-8, presumably by cross-linking and activating receptors of the death
      receptor family; ii) oxidative stress is possibly involved in the Abeta-induced
      cytotoxic effect; and iii) these two mechanisms do not act sequentially but,
      probably, are independent of each other.

PMID- 16465390
TI  - Plasminogen activator inhibitor-1 is locked in active conformation and
      polymerizes upon binding ligands neutralizing its activity.
AB  - Plasminogen activator inhibitor-1 (PAI-1), a member of the serpin super-family,
      forms a covalent complex with its target proteinases, such as tissue and
      urokinase plasminogen activators. Thus, PAI-1 controls the physiological and
      pathological proteolysis. An abnormal expression of PAI-1 has been observed in
      different diseases, which can be treated by returning the proteolysis back to
      normal physiological levels. It has been reported that some PAI-1 inhibitors
      neutralize its activity by accelerating the conversion of PAI-1 into a latent
      form. We have found small organic chemicals that also neutralize PAI-1 activity,
      but by a different mechanism. Using the NBD fluorescent probe [N,N'-dimethyl-N
      (acetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)] incorporated into the reactive
      center loop (RCL) of PAI-1, we measured the kinetics of conversion from an active
      to a latent form. Unexpectedly, we found that some inhibitors of PAI-1 arrest
      this serpin in its active form instead of increasing the speed of conversion.
      Using docking calculations, we located two possible binding sites for these
      chemicals. The sites are in proximity of the P1/P1' amino acids of the RCL of PAI
      1. Binding in this area can inactivate PAI-1 and additionally create a steric
      obstacle on the RCL making insertion of this loop between the A3 and A5 strands
      more difficult; hence abolishing a necessary step in the conversion of this
      protein into the latent form. Additionally, PAI-1 inhibitors link the RCL of one
      PAI-1 molecule with the strand 3C and strand 4C or helix A and strand 1B regions
      of the other PAI-1 molecule aiding polymerization or stabilizing the junction of
      the two. The polymerization of PAI-1 reduces PAI-1 activity by encapsulating the
      critical RCL fragment inside the formed PAI-1/PAI-1 polymers.

PMID- 16465391
TI  - Pro-inflammatory signaling by Jun-N-terminal kinase in inflammatory bowel
      disease.
AB  - Since Jun-N-terminal kinase participates in intracellular signaling cascades
      resulting in inflammatory responses, inhibiting this pathway may represent a new
      treatment for inflammatory bowel disease including ulcerative colitis and Crohn's
      disease. However, the functional significance of the activation of this kinase in
      inflammatory bowel disease remains unclear. We investigated whether Jun-N
      terminal kinase activation is increased in inflammatory bowel disease and
      analyzed the effects of SP600125, which decreases inflammatory cytokine synthesis
      by inhibiting the phosphorylation of this kinase. Phosphorylation of the kinase
      was examined in affected human colon using an enzyme-linked immunosorbent assay
      and immunohistochemistry. The effect of SP600125 on cytokine production was
      examined in cultures of patients' leukocytes and colonic tissue. Finally, rats
      received injection of SP600125 (30 mg/kg, s.c.) or vehicle twice daily 2 h before
      the induction of colitis with dextran sulfate sodium. SP600125 effects were
      determined observationally and histologically. Colonic tissue contained increased
      phosphorylated kinase in patients with inflammatory bowel disease with expression
      localized to the nucleus of epithelial and lamina propria mononuclear cells in
      lesions. Culturing mononuclear cells or colonic tissue with SP600125 down
      regulated inflammatory cytokine production. Prophylactic treatment with SP600125
      significantly reduced clinical and pathological scores in dextran sulfate sodium
      treated rats. This first demonstration of the pathogenetic role of Jun-N-terminal
      kinase in the development of intestinal inflammation suggests that inhibiting its
      phosphorylation could benefit patients with inflammatory bowel disease.

PMID- 16465393
TI  - Expression of cdc2 and p27(KIP1) phosphorylation in mitotic cells of the human
      retinoblastoma.
AB  - It was recently demonstrated that a lack of p27(KIP1) degradation resulted in the
      suppression of cdc2 activity and consequent inhibition of entry into the M-phase.
      The aim of this study was to examine the distribution of phosphorylated p27(KIP1)
      on threonine 187 (T187-phospho-p27) and cdc2 in mitotic cells of human
      retinoblastoma, a malignant retinal neoplasm. Several T187-phospho-p27
      immunopositive cells were observed in mitotic retinoblastoma cells, but not in
      the normal retina. Immunoreactivity for T187-phospho-p27 was located in the
      prophase and metaphase of mitotic tumor cells. In contrast, tumor cells in the
      anaphase showed no immunoreactivity for T187-phospho-p27. Nuclear expression of
      cdc2 was detected in many retinoblastoma cells, including mitotic cells. The
      immunoreactivity in mitotic cells was located in the prophase, as well as
      metaphase. In contrast, anaphase cells did not show immunoreactivity. Double
      staining demonstrated the same localization of T187-phospho-p27 and cdc2 in
      mitotic cells. These results suggest that p27(KIP1) interacts with cdc2 in the M
      phase of human retinoblastoma cells.

PMID- 16465392
TI  - Gene expression profile by inhibiting Raf-1 protein kinase in breast cancer
      cells.
AB  - Raf-1 protein serine-threonine kinase plays an important role in cell growth,
      proliferation, and cell survival. Previously, we and others have demonstrated
      that antisense raf oligonucleotide-mediated inhibition of Raf-1 expression leads
      to tumor growth arrest, radiosensitization and chemosensitization in vivo. Raf-1
      inhibition is also associated with apoptotic cell death. In this study, we
      inhibited Raf-1 using an antisense raf oligonucleotide (AS-raf-ODN) to identify
      downstream targets of Raf-1 using microarray gene expression analysis. Treatment
      of MDA-MB-231 breast cancer cells with 250 nM AS-raf-ODN led to significant
      inhibition of Raf-1 protein (75.2 +/- 9.6%) and c-raf-1 mRNA levels (86.2 +/-
      3.3%) as compared to untreated control cells. The lipofectin control or mismatch
      oligonucleotide had no effect on Raf-1 expression. To determine the changes in
      gene expression profiles that were due to inhibition of Raf-1, we simultaneously
      compared the gene expression patterns in AS-raf-ODN treated cells with untreated
      control cells and cells treated with lipofectin alone or MM-ODN. A total of 17
      genes (4 upregulated and 13 down-regulated) including c-raf-1 were identified
      that were altered after AS-raf-ODN treatment. Functional clustering analysis
      revealed genes involved in apoptosis (Bcl-XL), cell adhesion (paxillin, plectin,
      Rho GDIalpha, CCL5), metabolism (GM2A, SLC16A3, PYGB), signal transduction
      (protein kinase C nu), and transcriptional regulation (HMGA1), and membrane
      associated genes (GNAS, SLC16A3). Real-time PCR, Northern analysis and Western
      analysis confirmed the microarray findings. Our study provides insight into Raf-1
      related signaling pathways and a model system to identify potential target genes.

PMID- 16465394
TI  - Expression of telomerase (hTERT) in aldosterone-producing adrenocortical tumors.
AB  - Telomerase was found in cancers and immortalized cell lines, but only
      occasionally in normal tissues, thus suggesting that measurement of its hTERT
      subunit might help distinguishing benign from malignant tumors. Data on hTERT
      expression in adrenocortical tumors are scant and mostly confined to non
      functioning tumors. Therefore, we investigated whether hTERT expression may
      predict malignancy in aldosterone producing adrenocortical tumors. We measured
      hTERT mRNA with a real-time one-step reverse transcription (RT) polymerase chain
      reaction (PCR) method, based on the use of hTERT-specific fluorescence resonance
      energy transfer (FRET) probes, in 19 adrenalectomized patients with aldosterone
      producing adenomas (APAs), in whom long-term follow-up (median 7 years, range 5
      14 years) data were available. We also studied two rare aldosterone-producing
      carcinomas (APCs), eight adrenocortical carcinomas (ACs), twelve normal adrenal
      cortexes, and two malignant cell lines (NCI-295H and SW-13). Telomerase activity
      and hTERT immunoreactivity were also investigated. Of interest, we detected hTERT
      mRNA in 58% of APAs at levels similar to those of malignant tumors, which all
      consistently showed hTERT expression. In hTERT expressing tumors,
      immunocytochemistry showed the nuclear expression of hTERT. No hTERT expression
      was found in the normal adrenocortical tissue. No histopathology differences were
      observed between hTERT-positive and -negative APAs; however, a patient originally
      held to have an hTERT-positive APA was retrospectively classified as APC because
      of metastatic spread. In conclusion, RT-PCR measurement of hTERT mRNA is a
      hallmark of malignant adrenocortical tumors, but identifies also a subset of
      hTERT-expressing APAs that might show metastatic spread at long-term follow-up.

PMID- 16465395
TI  - c-Met responsiveness of isolated hepatocytes evaluated in an in vitro de
      differentiation model.
AB  - Hepatocyte growth factor (HGF) accelerates tissue regeneration and ameliorates
      tissue fibrosis through its ligand c-Met receptor tyrosine kinase. Hence, HGF is
      currently discussed as an attractive therapeutic candidate for fatal liver
      diseases. However, it remains unclear whether c-Met of de-differentiated
      hepatocytes adequately responds to HGF in an impaired liver. Therefore, we
      investigated c-Met expression and c-Met responsiveness to HGF in an experimental
      de-differentiation cell culture system. Primary rat hepatocytes were seeded on a
      two-dimensional collagen matrix or embedded within a three dimensional collagen
      gel to guarantee intact cell geometry. Cells were cultivated in a growth factor
      enriched extracellular milieu (de-differentiation medium), or in a chemically
      defined differentiation medium, representing physiologically intact hepatocytes.
      c-Met surface expression was determined by flow cytometry. Receptor localisation
      was examined by confocal microscopy, c-Met and phosphorylated c-Met protein were
      determined by western blotting. Hepatocyte-specific asialoglycoprotein receptor
      (ASGPr) was examined to control the differentiation status of the cells. Growth
      factor enriched milieu induced a rapid loss of ASGPr with a significant increase
      of c-Met surface level and a decrease in c-Met protein level. Surprisingly, the
      increased amount of c-Met surface expression was associated with its loss of
      responsiveness to HGF. The addition of bile acids into the culture medium had
      significantly delayed the process of de-differentiation and restrained the
      drastic elevation of c-Met (tauroursodeoxycholic acid > ursodeoxycholic acid).
      Application of the three-dimensional hepatocellular architecture stabilized the c
      Met surface receptor level and rendered c-Met activation. We have demonstrated
      that growth factor enriched extracellular milieu and loss of intact liver
      architecture seems to be accompanied by an up-regulation of c-Met surface level.
      Our findings suggest that irresponsiveness of c-Met to soluble HGF was possibly
      caused by an excessive HGF production and receptor over-stimulation. Both events
      should be considered when establishing an HGF-based therapy for
      fibrosis/cirrhosis.

PMID- 16465396
TI  - Gastrointestinal cancer - only a deregulation of stem cell differentiation?
      (Review).
AB  - Recent research on embryonic and adult stem cells questions the currently
      accepted models of multi-step carcinogenesis in solid cancer. Accordingly,
      differentiated epithelial cells are considered to be the main target for
      mutational steps, leading to a growth and survival advantage of malignantly
      transformed cells. In contrast, the stem cell model of carcinogenesis emphasizes
      the role of stem cells as the initiating structure for tumor development. Yet, it
      is unclear if tumors contain dysregulated (embryonic) stem cells or if tumors
      consist of differentiated adult cells that obtained a de-differentiated stem cell
      like phenotype. Here, we review the current knowledge on the roles of stem cells
      in gastrointestinal cancer formation and the implication on future diagnostic and
      therapeutic strategies.

PMID- 16465397
TI  - Expression of zinc finger protein ZPR1 mRNA in brain is up-regulated in mice fed
      a high-fat diet.
AB  - A differential display was performed to analyze differential gene expression in
      the brain of mice in association with dietary high beef tallow. Consumption of a
      high beef tallow diet up-regulated the expression of zinc finger protein ZPR1
      mRNA in the brain. Expression of ZPR1 mRNA in the cerebellum and hippocampus was
      elevated in response to the high beef tallow diet. The increased ZPR1 expression
      in the neuronal, Neuro-2A cells, caused a significant increase in H(2)O(2)
      induced cell death. These results suggest that a high beef tallow diet up
      regulates ZPR1 mRNA expression in the brain and might increase the vulnerability
      to oxidative stress.

PMID- 16465398
TI  - Effect of a novel water-soluble vitamin E derivative as a cure for TNBS-induced
      colitis in rats.
AB  - Lipid peroxidation mediated by oxygen free radicals plays an important role in
      the pathogenesis of inflammatory bowel disease (IBD). Vitamin E is a lipid
      soluble antioxidant and is generally considered to protect against lipid
      peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide
      anion radical. Therefore, vitamin E or its derivatives are expected to have
      particular application for patients suffering from IBD. The aim of this study was
      to investigate the antioxidative effects of the water-soluble vitamin E
      derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6
      ol(TMG), on the therapy of experimental colitis in rats. Colitis was induced in
      male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid
      (TNBS) dissolved in 50% ethanol; TMG dissolved in physiological saline was
      injected intra-peritoneally every day from 24 h after the enema of TNBS. The
      damage score, wet weight of the colon, and increase in body weight were estimated
      1 week after the enema of TNBS. Thiobarbituric acid-reactive substances (TBA-RS),
      an index of lipid peroxidation, and tissue-associated myeloperoxidase (MPO)
      activity in the colonic mucosa were measured 1 week after the induction of
      colitis. As a result, increase in body weight was inhibited by the induction of
      colitis, although the inhibition was reduced in the group treated with TMG. The
      damage score, wet weight, TBA-RS and MPO activity were increased significantly in
      the colitis group; however, they were inhibited by the administration of TMG.
      These results suggest that TMG is effective for the treatment of colitis in rats
      induced by TNBS. In the future, TMG could be a new therapeutic agent for IBD.

PMID- 16465400
TI  - Evaluation of the anti-allergic activity of Citrus unshiu using rat basophilic
      leukemia RBL-2H3 cells as well as basophils of patients with seasonal allergic
      rhinitis to pollen.
AB  - The anti-allergic activity of the 50% methanol extract of Citrus unshiu powder
      (MEC) was examined. Fifty percent methanol extract of MEC powder showed potent
      inhibitory activity against histamine release from basophils of patients
      suffering from seasonal allergic rhinitis to ceder pollen. To examine this anti
      allergic mechanism in detail, we next used rat basophlilic leukemia RBL-2H3
      cells. MEC significantly inhibited IgE-induced histamine and beta-hexosaminidase
      release from RBL-2H3 cells. Since MEC contains a variety of flavonoids, we
      selected nobiletin, hesperetin, and hesperidin (hesperetin glycoside) as
      representative compounds, and further evaluated these inhibitory activities.
      Among the flavonoids tested, hesperetin was the most potent, while hesperidin had
      far less, if any, inhibitory activity. The mechanism by which flavonoids
      inhibited the degranulation process was then examined. As a result, hesperetin
      and nobiletin suppressed the phosphorylation of Akt-1, direct downstream effector
      of phosphatidylinositol 3-kinase (PI3-K). Thus, it was assumed that these
      flavonoids suppressed IgE-mediated stimulation of basophils through PI3-K pathway
      and that proper intake of Citrus unshiu would be favorable for managing seasonal
      allergic rhinitis to ceder pollen.

PMID- 16465399
TI  - Repeated intravenous injection of recombinant human hepatocyte growth factor
      ameliorates liver cirrhosis but causes albuminuria in rats.
AB  - Hepatocyte growth factor (HGF) is a promising agent for the treatment of liver
      cirrhosis because of its mitogenic and anti-fibrotic effects. We investigated the
      effect of recombinant human HGF (rh-HGF) on cirrhosis development; its
      pharmacokinetics and nephrotoxicity in rats with liver cirrhosis induced by 4
      week treatment with dimethylnitrosamine (DMN). rh-HGF (0.3 mg/kg) was
      intravenously administered to rats once a day for 4 weeks in parallel with DMN
      treatment or twice a day for the last 2 weeks of DMN treatment. Repeated doses of
      rh-HGF increased the liver weight and serum albumin, and reduced serum ALT. The
      development of hepatic fibrosis was inhibited more efficiently by extended low
      dose treatment with rh-HGF. In cirrhotic rats, serum levels of rh-HGF increased
      and clearance was decreased, leading to an increase in the area under the plasma
      concentration time curve and a decrease in the steady-state volume of
      distribution. Repeated doses of rh-HGF led to increased urinary albumin
      excretion, but no rh-HGF-treated animals developed increased serum creatinine
      levels. Urinary albumin excretion returned to baseline after the cessation of rh
      HGF. These results suggest that extended treatment with rh-HGF is required for
      the attenuation of cirrhosis, and repeated doses of rh-HGF cause adverse effects
      in extra-hepatic organs. These issues must be resolved before the widespread
      application of rh-HGF in the treatment of liver cirrhosis.

PMID- 16465401
TI  - Fructokinase activity in rat liver, ileum, parotid gland, pancreas, pancreatic
      islet, B and non-B islet cell homogenates.
AB  - The presence of fructokinase (ketohexokinase) in rat pancreatic islet homogenates
      was previously documented. However, no information was so far available on the
      activity of this enzyme in islets relative to that in other tissues and on the
      respective contribution of insulin-producing B cells and non-B islet cells. The
      present study provides such an information. The activity of fructokinase, as
      assessed by the phosphorylation of 1.0 mM D-fructose, was compared to that of
      hexokinase isoenzyme(s), as measured in the presence of 1.0 mM D-glucose, and
      further characterized by its heat-resistance, K+ dependency and resistance to the
      inhibitory action of D-mannoheptulose. As judged from the results obtained in
      heated homogenates, the activity of fructokinase, expressed relative to protein
      content (nmol/min per mg protein) was highest in liver (21.5 +/- 2.5; n = 11) and
      lowest in parotid gland (0.16 +/- 0.09; n = 3), with in-between values in ileum
      (2.45 +/- 0.53; n = 3), pancreas (0.82 +/- 0.11; n = 11) and pancreatic islets
      (0.46 +/- 0.07; n = 6). The paired ratio between fructokinase and hexokinase
      isoenzyme activity was also highest in liver (548 +/- 45%; n = 8) and lowest in
      parotid gland (0.93 +/- 0.52%; n = 3). Such a ratio was not significantly
      different in pancreas, islets and purified B or non-B islet cells, with an
      overall mean value of 2.57 +/- 0.46% (n = 12). The present findings thus
      unambiguously document the presence of fructokinase activity in all cell types
      under consideration, except possibly parotid cells, with the following hierarchy:
      liver > ileum > pancreas. Relative to paired hexokinase activity, no obvious
      difference was found for fructokinase activity in B versus non-B islet cells.

PMID- 16465402
TI  - Gene expression in mouse spermatogenesis during ontogenesis.
AB  - In this study, we evaluated the expression of genes probably involved in
      spermatogenesis in the mouse. We examined cytosolic chaperonin theta subunit
      (CCTtheta), Ngg1 interacting factor 3 like 1 binding protein 1 (NIF3L1 BP1) and
      apolipoprotein H (ApoH) expression during mouse onto-geny using RT-PCR.
      Testicular tissue was obtained from mice 3, 6, 8, 10, 12, 14, 18, 20 and 40
      (adult) days after birth. For each mouse, one testis was used for histological
      examination, whereas RNA was extracted from the controlateral testis for
      expression analysis. RT-PCR analysis showed that CCTtheta gene expression was low
      until day 10, but increased drastically afterwards. At this age, spermatocytes
      started to be present in the mouse testis. Therefore, CCT protein could be
      involved in chromatin packaging and remodeling during spermiogenesis, as also
      suggested by other studies. NIF3L1 BP1 expression increased steadily during
      ontogenesis reaching maximum levels in the adult mouse when all germ cell stages
      are present. This finding suggests that NIF3L1 BP1 is a gene not expressed by a
      specific germ cell type. ApoH expression was very low or absent during prepuberal
      stages, whereas it was detectable in the adult testis when spermatogenesis was
      completed. This suggests that ApoH may be involved in clearing apoptotic bodies
      during spermatogenesis since apoptotic events increase during spermatogenesis.
      This study contributes to understanding the role played by genes important for
      spermatogenesis.

PMID- 16465403
TI  - FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT
      signaling pathway in progenitor cells.
AB  - WNT, FGF and Hedgehog signaling pathways network together during embryogenesis,
      tissue regeneration, and carcinogenesis. FGF16, FGF18, and FGF20 genes are
      targets of WNT-mediated TCF/LEF-beta-catenin-BCL9/BCL9L-PYGO transcriptional
      complex. SPROUTY (SPRY) and SPRED family genes encode inhibitors for receptor
      tyrosine kinase signaling cascades, such as those of FGF receptor family members
      and EGF receptor family members. Here, transcriptional regulation of SPRY1,
      SPRY2, SPRY3, SPRY4, SPRED1, SPRED2, and SPRED3 genes by WNT/beta-catenin
      signaling cascade was investigated by using bioinformatics and human intelligence
      (humint). Because double TCF/LEF-binding sites were identified within the 5'
      promoter region of human SPRY4 gene, comparative genomics analyses on SPRY4
      orthologs were further performed. SPRY4-FGF1 locus at human chromosome 5q31.3 and
      FGF2-NUDT6-SPATA5-SPRY1 locus at human chromosome 4q27-q28.1 were paralogous
      regions within the human genome. Chimpanzee SPRY4 gene was identified within
      NW_107083.1 genome sequence. Human, chimpanzee, rat and mouse SPRY4 orthologs,
      consisting of three exons, were well conserved. SPRY4 gene was identified as the
      evolutionarily conserved target of WNT/beta-catenin signaling pathway based on
      the conservation of double TCF/LEF-binding sites within 5'-promoter region of
      mammalian SPRY4 orthologs. Human SPRY4 mRNA was expressed in embryonic stem (ES)
      cells, brain, pancreatic islet, colon cancer, head and neck tumor, melanoma, and
      pancreatic cancer. WNT signaling activation in progenitor cells leads to the
      growth regulation of progenitor cells themselves through SPRY4 induction, and
      also to the growth stimulation of proliferating cells through FGF secretion.
      Epigenetic silencing and loss-of-function mutations of SPRY4 gene in progenitor
      cells could lead to carcinogenesis. SPRY4 is the pharmacogenomics target in the
      fields of oncology and regenerative medicine.

PMID- 16465404
TI  - Intracellular viability in human non-polarized respiratory epithelial 16 HBE 14o-
      cells by group B Streptococcus serotype III clinical isolates presenting 162-kb
      and 183-kb virulence markers.
AB  - Group B streptococci (GBS), mainly serotype III, are the major cause of neonatal
      pneumonia, sepsis and meningitis. Virulence potential of GBS strains may
      determine the outcome of host colonization or infection. Because the lung
      constitutes a first step in GBS systemic invasion processes, we investigated the
      adherence and invasion mechanisms of GBS-III clinical isolates to non-polarized
      human bronchial epithelial 16 HBE 14o- cell line. The presence of genotypic 162
      kb and 183-kb virulence markers in all strains was also examined by PFGE. The 162
      kb fragment was detected in both liquor (GBS-III 90356) and vagina (GBS-III 39A)
      isolates, while 183-kb fragment was only observed in strains (GBS-III 39A, 89A,
      and 80340) isolated from vagina of asymptomatic carriers. The actin-dependent
      ability to internalize within non-polarized epithelial respiratory cells was
      demonstrated only by GBS-III clinical isolates presenting the 162-kb virulence
      marker. GBS-III 39A strain isolated from vagina exhibiting both 183-kb and 162-kb
      fragments showed a more efficient adherence and invasion properties than GBS-III
      90356 isolated from liquor (P<0.001). Our data suggest the expression of
      additional bacterial virulence factors that may favor adherence and survival to
      non-polarized respiratory epithelial cells with consequent development of
      systemic diseases by GBS-III, including some strains isolated from asymptomatic
      carriers.

PMID- 16465405
TI  - Six novel mutations of the LDL receptor gene in FH kindred of Sicilian and
      Paraguayan descent.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease
      caused by mutations in the gene coding for the low density lipoprotein receptor
      (LDL-R). It is characterized by a high concentration of low density lipoprotein
      (LDL), which frequently gives rise to premature coronary artery disease. We
      studied the probands of five FH Sicilian families with 'definite' FH and one
      proband of Paraguayan descent with homozygous FH who has been treated with an
      effective living-donor liver transplantation. In order to seek the molecular
      defect in these six families, we used direct sequencing to define the molecular
      defects of the LDL-R gene responsible for the disease. We described three novel
      missense mutations (C100Y, C183Y and G440C), two frameshift mutations (g.1162delC
      in exon 8 and g.2051delC in exon 14) and one mutation (g.2390-1Gright curved
      arrow A) at splicing acceptor consensus sequences located in intron 16 of the LDL
      R gene; the analysis of cDNA of this splicing mutation showed the activation of a
      cryptic splice site in intron 16 and the binding studies showed a reduction in
      internalisation of LDL-DIL in the proband's cultured fibroblasts. Moreover, a
      g.2051delC in exon 14 was identified in the proband of Paraguayan ancestry with
      clinical features of homozygous FH. The mutation identified in the South American
      patient represents the first description of a variant in South American patients
      other than Brazilian FH patients. The 5 mutations identified in the Sicilian
      patients confirm the heterogeneity of LDL-R gene mutations in Sicily.

PMID- 16465406
TI  - Evaluation of human fetal bone implants in SCID mice as a model of prostate
      cancer bone metastasis.
AB  - The metastasis of prostate cancer cells to the bone marrow constitutes the major
      source of morbidity and mortality in prostate cancer. Studying this process has
      been hampered by the lack of preclinical models to evaluate novel therapeutics
      and to study the biology of the disease. One proposed model utilizes human fetal
      bone implants to serve as the target for prostate cancer cells injected via the
      tail vein. We employed this model to test the ability of zoledronic acid to
      prophylax and to treat bone metastases. To improve the rate of bone metastasis,
      we used two bone implants instead of one to evaluate the cell lines PC3 and PC3M,
      a more metastatic subline. For this purpose we generated the novel cell line
      PC3EGFPLuc, which can be used for luminescence and/or fluorescence imaging in
      vivo. We did not observe bone implant metastases in 52 mice, with 90 bone
      implants following tail vein injection of 1x10(6) PC3 or PC3M cells. Soft tissue
      lesions in the buttocks and hind limbs as well as cellular growth in the
      hindlimbs were observed via bioluminescence imaging. This evidence together with
      literature findings suggests that this model produces artifactual 'bone
      metastasis' lesions.

PMID- 16465407
TI  - Angiogenesis in cholangiocellular carcinoma: expression of vascular endothelial
      growth factor, angiopoietin-1/2, thrombospondin-1 and clinicopathological
      significance.
AB  - Angiogenesis in cholangiocellular carcinoma (CCC) has rarely been investigated.
      The aim of this study was to determine the angiogenesis status of CCC and assess
      its relationship with angiogenic factors and clinicopathological characteristics.
      We examined 33 surgically resected CCC specimens. Tumor angiogenesis was assessed
      by microvessel density (MVD) using the anti-CD34 antibody, and the expression of
      VEGF, Ang-1, Ang-2, and TSP-1 was determined by immunohistochemistry. The mean
      (+/- SD) MVD was 87.2+/-52.6/mm2 (range, 0-229/mm2). A total of 75.6% cases were
      positive for VEGF expression, 36% for Ang-1, 57.6% for Ang-2 and 45.5% for TSP-1.
      VEGF and Ang-2 expression was associated with a significantly higher level of MVD
      (p=0.004 and 0.015, respectively). TSP-1 expression was associated with a
      significantly lower level of MVD (p=0.005) and a higher level of intrahepatic
      metastasis (46.7% vs. 5.6%, p=0.012). There was no significant correlation
      between VEGF, Ang-1, Ang-2, and TSP-1 expression and tumor size, capsule
      formation, infiltration of capsule, portal vein invasion, intrahepatic metastasis
      or CCC differentiation. There was no significant correlation between MVD levels,
      VEGF, Ang-1, Ang-2, and TSP-1 expression and postoperative survival. A
      considerable degree of angiogenesis, comparable to that of other solid tumors,
      was observed in CCC. VEGF and Ang-2 might play a proangiogenic role, and TSP-1
      may play an inhibitory role in CCC. Although TSP-1 may increase intrahepatic CCC
      metastases, neither MVD levels nor the expression of VEGF, Ang-1, or Ang-2 was
      associated with clinicopathological factors and prognosis.

PMID- 16465408
TI  - Chemoprevention of mouse urinary bladder carcinogenesis by fermented brown rice
      and rice bran.
AB  - Fermented brown rice by Aspergillus oryzae (FBRA) has been shown to be a potent
      anti-carcinogenic compound. Here, we investigated the modifying effects of
      dietary feeding with a naturally occurring anti-oxidant FBRA on N-butyl-N-(4
      hydroxybutyl)-nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis in male
      ICR mice. Five-week-old male ICR mice were divided into 7 groups, and groups 1-5
      were given OH-BBN (500 ppm) in drinking water for 6 weeks starting at 7 weeks of
      age. Groups 2 and 3 were fed the diet containing 5% and 10% FBRA during the
      initiation phase, respectively, whereas groups 4 and 5 were fed these diets
      during the post-initiation phase. Group 6 was given the diet containing 10% FBRA
      throughout the experiment, and group 7 was kept on the basal diet alone and
      served as an untreated control. At the end of the study (week 32), the incidences
      of simple hyperplasia, dysplasia and carcinoma in the bladders of group 1 (OH-BBN
      alone) were 92%, 49% and 38%, respectively. Those of group 5 (64%, 23% and 10%)
      and the incidence of carcinoma of group 4 (17%) was significantly less than that
      of group 1. Furthermore, the multiplicity of simple hyperplasia and carcinoma of
      group 5 was significantly less than that of group 1. Post-initiation exposure of
      10% FBRA significantly decreased the number/nucleus of silver-stained nucleolar
      organizer region proteins (AgNORs), an index of cell proliferation, in the non
      lesional transitional epithelium when compared to that of the control. Our
      results indicate that FBRA exerts chemopreventive effects against chemically
      induced urinary bladder carcinogenesis through anti-proliferative mechanisms.
      FBRA could be a promising chemopreventive agent for human urinary bladder cancer.

PMID- 16465409
TI  - Ubiquitin-specific protease 14 expression in colorectal cancer is associated with
      liver and lymph node metastases.
AB  - Ubiquitin-specific protease 14, also known as the 60 kDa subunit of tRNA-guanine
      transglycosylase (USP14/TGT60 kD), belongs to the ubiquitin-specific processing
      protease (UBP) family. USP14/TGT60 kD expression in leukemic and colorectal
      cancer cell lines, and the suppression of such an expression after the induction
      of cell differentiation have been reported. In the present study, we attempted to
      clarify whether USP14/TGT60 kD overexpression affects the clinicopathological
      features of colorectal cancer. Immunohistochemically, USP14/TGT60 kD was absent
      or weakly localized in the cytoplasm of normal colorectal epithelial cells. In 18
      of 99 (18.2%) colorectal cancer patients, USP14/TGT60 kD was strongly detected in
      the cytoplasm of cancer cells. USP14/TGT60 kD expression correlated with
      pathological stage (P=0.03), and lymph node (P=0.03) and liver (P=0.03)
      metastases. Furthermore, the percentage of patients strongly positive for
      USP14/TGT60 kD expression increased with pathological stage. The overall survival
      rate was worse in patients with a high USP14/TGT60 kD expression level than in
      those with a low USP14/TGT60 kD expression level. Our results suggest that
      USP14/TGT60 kD also controls the fate of proteins that regulate tumor invasion
      and metastasis.

PMID- 16465410
TI  - Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human
      lung cancer.
AB  - The ING1 gene is involved in the regulation of the cell cycle, senescence, and
      apoptosis and is a novel candidate tumor suppressor gene. ING2, another gene in
      the ING family, was identified and cloned. The functions of ING1 and ING2 largely
      depend on the activity of p53. To determine whether an alteration in these genes
      plays a role in carcinogenesis and tumor progression in lung cancer, we screened
      30 human lung cancer cell lines and 31 primary lung cancer tumors for mutations
      in these genes using polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and direct sequencing. Our findings failed to uncover any
      mutations in these genes. We also examined the expression of ING1 and ING2 in
      lung cancer cell lines that either had or lacked a p53 mutation, and in a control
      bronchial epithelium cell line, using quantitative real-time reverse
      transcription-polymerase chain reaction (RT-PCR). ING1 expression was up
      regulated in all 7 lung cancer cell lines that had a p53 mutation, while the
      expression of ING2 was down-regulated in 6 of 7 lung cancer cell lines that had a
      p53 mutation. These results suggest that the ING1 and ING2 genes have different
      roles in lung carcinogenesis and progression, and the ING2 gene may be an
      independent tumor suppressor candidate on p53.

PMID- 16465412
TI  - Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung
      carcinoid tumors: a novel approach using real-time PCR with melting curve
      analysis in histopathologic material.
AB  - The possible causes and genetic mechanisms of pulmonary carcinoid tumor
      development are unclear. In this study, we examined genetic alterations at the
      MEN1 locus in archival material from 15 pulmonary carcinoids. We employed, for
      the first time in this setting, real-time PCR with melting curve analysis in
      order to identify loss of heterozygosity (LOH) or microsatellite instability (MI)
      in two polymorphic markers (PYGM, D11S449) at the MEN1 locus and one additional
      marker (D11S906) of a putative oncosuppressive region distal to the MEN1 gene.
      Sequencing data were available in a selected subset of tumors in order to verify
      the reliability of real-time PCR analysis. We observed LOH at PYGM in 38% of the
      cases and MI in 13.3% of the cases. Our data indicate that real-time PCR with
      melting curve analysis is a reliable technique for LOH and MI detection and
      indicate that genetic errors at the MEN1 locus but also distal to it may be
      involved in the development of sporadic pulmonary carcinoid tumors.

PMID- 16465411
TI  - Diagnostic and prognostic impact of beta-catenin alterations in pediatric liver
      tumors.
AB  - Hepatoblastoma (HBL), a major childhood malignant neoplasm, represents the most
      frequent malignant liver tumor in childhood. Recent reports have shown the CTNNB1
      coding beta-catenin protein to be frequently mutated or deleted at hot-spot
      regions involving exon 3 in HBL. We investigated the genetic alterations of the
      CTNNB1 coding beta-catenin protein and expression of several genes downstream of
      Wnt signals in 4 benign and 17 malignant pediatric liver tumors (PLTs) consisting
      of 15 HBL, 1 hepatocellular carcinoma, and 1 hepatic immature sarcoma. Of 17
      malignant PLTs, 10 (56%) revealed pathogenic alterations of the CTNNB1 gene,
      including 4 with missense mutations at codons 28, 32, 34 or 44, and 6 with
      interstitial deletions that partially or totally affected exon 3. All 6 deletions
      were in-frame deletions without a frame shift. The high frequency without any
      correlation to histological type indicates that the CTNNB1 gene alteration is a
      crucial event in the tumorigenesis of malignant PLTs. The immunohistochemical
      studies in 17 malignant PLTs demonstrated the nuclear/cytoplasmic accumulation of
      beta-catenin to be positive in all tumor specimens except for one hepatic
      sarcoma. A histological examination revealed all HBL cases involving tumors
      without detectable CTNNB1 gene alterations to show high expression of beta
      catenin, thus indicating the accumulation of beta-catenin to be a common event in
      malignant PLTs, including HBL and hepatocellular carcinoma. Among the Wnt signal
      genes downstream of beta-catenin, E-cadherin is expressed in all malignant PLTs,
      while cyclin D1 expression was significantly detected in malignant PLTs with an
      advanced stage of disease. An immunohistological examination of nuclear
      accumulation of beta-catenin may thus be useful for diagnosing malignant PLTs. On
      the other hand, the expression of cyclin D1, a gene downstream of beta-catenin,
      might play a role in tumor progression.

PMID- 16465413
TI  - Germline mutations of BRCA1 in two Korean hereditary breast/ovarian cancer
      families.
AB  - Testing for cancer susceptibility gene, in particular mutations in the BRCA1 gene
      in association with hereditary breast/ovarian cancer has been extensively
      studied. We investigated germline mutations in the BRCA1 gene from two Korean
      hereditary breast/ovarian cancer families using direct DNA sequencing. Blood
      samples of the thirteen family members were studied. We found three missense
      mutations; 3232 Aright curved arrow G, 2731 Cright curved arrow T, 3667 Aright
      curved arrow G. These mutations were involved in the altered coding of amino
      acids. According to the BIC database, clinical significance of these mutations is
      regarded as favor polymorphisms. Therefore, these genetic variations are not
      believed to be involved in the development of the disease, but may be associated
      with breast/ovarian cancers in another yet undefined way. For further clinical
      significance of these variations, additional study such as a case-controlled
      haplotyping study is needed.

PMID- 16465414
TI  - Amurubicinol-induced eotaxin-3 expression in human NCI-H69 small cell lung
      carcinoma cells.
AB  - We previously demonstrated the doxorubicin-induced expression of urokinase-type
      plasminogen activator (uPA), interleukin-8 (IL-8), monocyte chemoattractant
      protein-1 (MCP-1) and tumor necrosis factor-alpha in human RC-K8 lymphoma cells
      and NCI-H69 small cell lung carcinoma cells in which reactive oxygen species
      might be involved. Amurubicin hydrochloride (AMR), a novel derivative drug of
      doxorubicin, was recently introduced to clinical practice for treatment of lung
      cancer in Japan. Therefore, we investigated the effects of AMR on the expression
      of uPA and chemokines in NCI-H69 cells. AMR and its active form, amurubicinol
      hydrochloride (AMROH), both induced the expression of uPA, IL-8 and MCP-1 in H69
      cells in a dose-dependent manner. When the cultured supernatant obtained from AMR
      treated H69 cells was subcutaneously injected into rabbits, migration of a
      significant number of eosinophils was observed around the injected site. Antigen
      levels of eotaxin-3, a major migration-factor of eosinophils, were increased in
      AMROH-treated cells in parallel with the mRNA levels. The induction was observed
      below the clinically achievable concentration of AMR or AMROH. Thus, the
      simultaneous induction of uPA, IL-8, MCP-1 and eotaxin-3 may play a role in the
      pharmacological action of AMR through induction of the interaction between
      proinflammatory cells and lung carcinoma cells.

PMID- 16465415
TI  - Low doses of alpha particle irradiation modify the expression of genes regulating
      apoptosis in human MCF-7 breast cancer cells.
AB  - The possibility of modifying apoptosis-related genes in tumor cells is an
      interesting line of research that calls for multidisciplinary experimentation to
      describe its characteristics and the conditions required. In vitro low doses of
      alpha particle irradiation due to radon have an antiproliferative effect on the
      growth of MCF-7 cells and increase the sensibility of cancer cells to taxol, a
      chemotherapeutic agent that induces cellular apoptosis. The present study
      examines the in vitro effects of low doses of alpha particle irradiation from the
      gas radon on the expression of some bcl-2 family apoptosis-related genes. The
      analyzed genes were bax, bcl-2 and bcl-x, with known responses to genotoxic
      stress (bcl-2) or ionising radiation (bax and bcl-x) in MCF-7 human breast cancer
      cells. The results obtained indicate that the cell line studied expresses the
      mentioned genes and they demonstrate that irradiation with low radon doses of MCF
      7 cells induces underexpression of both bax and bcl-2 genes. Interestingly, the
      mRNA levels of the full-length bcl-x gene (bcl-xL) were overexpressed after
      irradiation, and we found significant mRNA levels of an alternative mRNA splicing
      form of the same gene (bcl-xS), which enhances the apoptotic sensitivity of the
      cell. The increased sensitivity to apoptosis resulting from bcl-xS overexpression
      is important because it might improve the efficacy of chemotherapeutic agents
      used to treat cancers which act through induction of apoptosis. The finding that
      low radiation doses of alpha particles from the gas radon modulate the expression
      of apoptosis-related genes suggests a therapeutic utility for this naturally
      occurring agent.

PMID- 16465416
TI  - The reactivity to CK5/6 antibody in tumor cells from non-small cell lung cancers
      shed into pleural effusions predicts survival.
AB  - Lung cancer, especially adenocarcinoma and large cell carcinoma, tends to spread
      to the pleural cavities. Once an effusion develops, the prognosis is generally
      dismal. Immunocytochemistry is frequently applied to effusions for diagnostic
      purposes, but the prognostic value of markers in malignant effusions have thus
      far attracted less attention. Dakopatts CK 5/6 antibody was applied to ethanol
      fixed fresh cytospin preparations from malignant pleural effusions originating
      from 18 patients (11 men and 7 women) with a previously or later verified non
      small cell lung carcinoma (NSCLC). In three cases, CK5/6 reactivity was found in
      part of the malignant population, whereas 10 cases showed reactivity in most
      tumor cells. The lack of reactivity in malignant cells was only seen in five
      effusions. Females showed significantly lower reactivity rates, with all negative
      effusions coming from female patients, whereas 9/10 effusions with reactivity in
      most malignant cells originated from males. CK5/6 reactivity was significantly
      correlated to survival, with a median survival time of 18 days for patients with
      CK5/6-negative tumors, and 212 days for those with positive tumors. The strong
      relationship between CK5/6 reactivity and survival, and the observed gender
      difference, warrants larger studies aimed at the clinical utility of CK5/6 as a
      prognostic marker in metastatic NSCLC, the possible functional role of CK5/6 in
      cell adhesion in advanced NSCLC and its possible hormonal control.

PMID- 16465417
TI  - Expression of c-Src and comparison of cytologic features in cherubism, central
      giant cell granuloma and giant cell tumors.
AB  - Cherubism (CBM) and central giant cell granuloma (CGCG) of the jaw and giant cell
      tumor (GCT) of the long bone are clinically different diseases. Histologically,
      they are all multinucleated giant cell (MGC)-containing lesions. This study aims
      to evaluate the expression of c-Src and cytologic features in CBM, CGCG and GCT
      and to clarify whether there is a common mechanism underlying the formation of
      multi-nucleated giant cells (MGCs) in these lesions. Specimens and paraffin
      blocks were collected from patients with CBM (12 cases), CGCG (24 cases) and GCT
      (37 cases). Histomorpho-metric differences in MGCs were compared among the three
      types of lesions. The expression of c-Src by immunohistochemistry and in situ
      hybridization and the expression of TRAP by enzyme histochemical staining were
      examined. Expression of c-Src mRNA and protein, as well as TRAP staining, was
      detected in both MGCs and a fraction of mononuclear cells in all investigated
      lesions. There are no quantitative differences for cytologic features and c-Src
      expression among the lesions. The results suggested that CBM, CGCG and GCT have
      overlapping cytological features at the histological level, and c-Src may be
      involved in the formation of MGCs in the three different diseases.

PMID- 16465418
TI  - Increased expression of CCAAT/enhancer binding protein beta correlates with
      prognosis in glioma patients.
AB  - C/EBP beta (CCAAT/enhancer binding protein beta) is a transcriptional factor that
      belongs to the basic region-leucine zipper class DNA-binding proteins and plays a
      role in cell differentiation and inflammatory reactions. Although high tissue
      levels of inflammatory cytokines, such as interleukin (IL)-6, IL-8 and
      transforming growth factor-beta, have been observed in glioma patients, the
      mechanisms underlying this phenomenon remain to be elucidated. C/EBP beta induces
      a variety of cytokines and thus may play a role in the pathogenesis of glioma. In
      this study, we investigated the relationship between C/EBP beta expression, tumor
      histology, and prognosis in glioma. The expression of C/EBP beta mRNA was
      examined with quantitative real-time PCR and protein expression was examined with
      immunohistochemical techniques in 47 glioma tissue samples. Expression of C/EBP
      beta mRNA and protein was markedly increased in high grade glioma compared with
      low grade glioma. Patients whose expression of C/EBP beta mRNA and protein in
      tumor tissue was lower survived longer than those whose expressions were higher.
      In vitro, C/EBP beta siRNA inhibited glioma cell proliferation and invasion.
      Moreover, IL-8 production by glioma cells was inhibited by C/EBP beta siRNA
      transfection. These data suggest that increased expression of C/EBP beta may
      contribute to the promotion of tumor invasiveness and progression. The data imply
      that the comparison of C/EBP beta expression could be a prognostic marker for
      patients with glioma.

PMID- 16465419
TI  - Ethanol stimulates the secretion of matrix metalloproteinases 2 and 9 in MCF-7
      human breast cancer cells.
AB  - Alcohol consumption is a well-established risk factor for hormone-dependent
      breast cancer. In vitro studies performed to understand the mechanisms by which
      ethanol acts on breast cancer cells have shown that this compound stimulates both
      proliferation and migration. In the present study, we show by gelatin zymography
      that, when exposed to ethanol, MCF-7 human breast cancer cells display a higher
      amount of active metalloproteinases (MMP) 2 and 9 in their culture medium. This
      increase is somewhat higher than those observed in the case of 17beta-estradiol
      (E2) exposure. As expected, anti-estrogen ICI 182,780 inhibits the E2-induced
      overexpression of a well-known estrogen responsive gene, the progesterone
      receptor, in MCF-7 cells. ICI 182,780 also inhibits the E2-induced increase in
      MMP-2 and -9 secretion. Nevertheless, in the case of ethanol exposure, this ER
      ant-agonist was only efficient on MMP-9 secretion. In addition, although MMP-9
      transcription was not sensitive to E2 or ethanol, MMP-2 transcription was
      stimulated in MCF-7 cells exposed to ethanol. Collectively, these results give
      new insights into the effects of alcohol on breast cancer cell migration, which
      are not due solely to an estrogen-like activity of alcohol.

PMID- 16465420
TI  - Differential expression of nuclear lamins in normal and cancerous prostate
      tissues.
AB  - The process of carcinogenesis is characterized by definite changes in the protein
      composition of the nuclear matrix. We have recently found that lamins form, in
      addition to the nuclear lamina, an intranuclear web of thin fibrils. This finding
      prompted us to address the question of whether changes in the expression of
      lamins occur in the course of tumor development. In prostate cancer, lamin B
      undergoes a significant increase; interestingly, its nuclear content strongly
      correlates with tumor differentiation. Moreover, all the lamins show reproducible
      alterations in the distribution of the isoelectric variants, suggesting that
      dephosphorylation events could trigger changes in the pattern of gene expression
      by inducing structural rearrangements of the nuclear scaffold.

PMID- 16465421
TI  - Frequent p16 CpG island hypermethylation in primary remnant gastric cancer
      suggesting an independent carcinogenic pathway.
AB  - Cancer found in the post-operative remnant stomach includes both newly developed
      cancer after surgery for benign-disease (PRC) and metachronous multiple cancer
      (MRC). Differences in the carcinogenic pathway between PRC and MRC have been
      suspected from clinical studies. However, no study has demonstrated the
      difference in molecular alteration between these diseases. P16 is inactivated
      predominantly by epigenetic change, rather than genetic alteration. We analyzed
      the methylation status and protein expression of the p16 gene in cancers of the
      remnant stomach. Eleven lesions of PRC, 24 lesions of MRC and corresponding non
      cancerous tissue, as well as 13 primary gastric cancer (PC) lesions were
      examined. DNA was extracted by the micro-dissection method from paraffin-embedded
      surgical specimens. The methylation status of the promoter CpG island of the p16
      gene was examined by using a methylation-specific polymerase chain reaction
      technique. To detect protein expression, immunohistochemical staining was
      employed. p16 promoter hypermethylation was observed more often in remnant
      gastric cancer than in PC. A significantly more frequent hypermethylation in the
      p16 gene was found in PRC (64%) than in MRC (21%) or PC (23%). Moreover, a
      significant correlation was found between p16 promoter hypermethylation and
      diminishment of protein expression in cancers of the remnant stomach. Silencing
      of the p16 gene by methylation of its promoter CpG island was suggested as a
      unique molecular mechanism in the carcinogenesis of PRC compared with MRC or PC.

PMID- 16465422
TI  - Paclitaxel and leucovorin-modulated infusional 5-fluorouracil combination
      chemotherapy for metastatic gastric cancer.
AB  - As no standard chemotherapy regimen has been established for advanced gastric
      cancer, this study sought to evaluate the efficacy and safety of combination
      chemotherapy that included paclitaxel and leucovorin (LV)-modulated infusional 5
      fluorouracil (5-FU) in metastatic gastric cancer. Patients received a three-hour
      infusion of 175 mg/m2 of paclitaxel on day 1. A bolus of 20 mg/m2 of LV was then
      administered, followed by a 24-h infusion of 1,000 mg/m2 of 5-FU on days 1
      through 3. The treatment cycle was re-peated every 3 weeks until disease
      progression. Response evaluation was performed according to the RECIST criteria,
      with toxicity determined by NCI-CTC (version 2.0). A total of 66 patients,
      including 21 (31.8%) with a history of prior chemotherapy, were enrolled. Fifteen
      (71.4%) of the 21 patients with prior chemotherapy received prolonged infusional
      5-FU. In the 56 evaluable patients (37 in the chemotherapy-naive group and 19 in
      the prior chemotherapy group), tumor responses according to prior exposure to
      chemotherapy were as follows: 17 (45.9%) partial response (PR), 6 (16.2%) stable
      disease (SD) and 14 (37.8%) progressive disease (PD) in the chemotherapy-naive
      group; 1 (7.1%) complete response, 3 (15.8%) PRs, 8 (42.1%) SDs and 7 (36.8%) PDs
      in the prior chemotherapy group. The overall median response duration was 20
      weeks (range, 8-61 weeks), with a median progression-free survival of 20 weeks
      [95% confidence interval (CI), 13.4-26.6 weeks] and 12 weeks (95% CI, 5.7-18.3
      weeks) in the chemotherapy-naive and prior chemotherapy groups, respectively. The
      median overall survival was 48 weeks (95% CI, 38-58 weeks) in the chemotherapy
      naive group and 28 weeks (95% CI, 22-34 weeks) in the prior chemotherapy group.
      The most frequent grade III/IV toxicity was neutro-penia. Non-hematological
      toxicity of grade III/IV was rare. Paclitaxel in combination with 5-FU/LV is
      clinically beneficial for patients with advanced gastric cancer and is a feasible
      salvage regimen for 5-FU-refractory gastric cancer patients.

PMID- 16465423
TI  - Heat-directed suicide gene therapy mediated by heat shock protein promoter for
      gastric cancer.
AB  - The prognosis of patients with metastatic gastric cancer, particularly peritoneal
      carcinomatosis, remains poor despite intensive interventions. Gene therapy and
      hyperthermia can be promising strategies for such advanced disease. The study was
      conducted to explore the possible effective therapeutic approach of suicide gene
      therapy with herpes simplex virus thymidine kinase (HSV-tk) in combination with
      hyperthermia for advanced gastric cancer. The heat shock protein (hsp) 70B gene
      promoter-oriented HSV-tk (HSP-tk)/ganciclovir (GCV) system directed by heat shock
      was developed. Hsp promoter activity under the control of heating was assessed by
      dual luciferase assay in gastric cancer cell lines and implanted tumors of nude
      mice. In vitro cytotoxic assay was performed using the HSP-tk/GCV delivered by
      the hemagglutinating virus of Japan (HVJ) liposome, with or without heating. Mice
      with subcutaneously xenografted tumors and peritoneal carcinomatosis were treated
      with hyperthermia and gene therapy using the HVJ-liposome-carrying HSP-tk.
      Assessment by luciferase assay demonstrated highly inducible and tumor-specific
      promoter activity in vitro and in vivo. Cytotoxic assays showed that cells
      transfected with HSP-tk became more sensitive to GCV with heating. A synergistic
      effect was also observed when treated with a non-heat-inducible cytomegalovirus
      (CMV) promoter-mediated HSV-tk/GCV and heating, indicating bystander killing. The
      HVJ-liposome-carrying HSP-tk/GCV combined with hyperthermia significantly
      inhibited the growth of subcutaneous tumors and prolonged survival of mice with
      peritoneal carcinomatosis. We conclude that the combination of suicide gene
      therapy with hyperthermia can provide a promising treatment modality for advanced
      gastric cancer.

PMID- 16465424
TI  - Growth-inhibitory effects of a beta-glucan from the mycelium of Poria cocos on
      human breast carcinoma MCF-7 cells: cell-cycle arrest and apoptosis induction.
AB  - Because of the reported immune-enhancing and anti-tumor activities of some
      mushroom polysaccharides, their applications as biological response modifiers
      have attracted significant attention. We have purified a water-soluble beta
      glucan PCM3-II, comprising mainly 1right curved arrow 3 and 1right curved arrow 4
      linkages, from the mycelia of Poria cocos (Schw.) Wolf (Fu-ling). In this study,
      the growth-inhibitory effect of PCM3-II was further explored on the human breast
      carcinoma MCF-7 cells in vitro. The dose effect of PCM3-II was studied by
      incubating the breast cancer cells with 12.5-400 microg/ml of the glucan for 72
      h. The MTT study showed that PCM3-II reduced proliferation and viability of the
      MCF-7 cells dose-dependently, so that the cancer-cell growth was decreased by 50%
      of the control level at 400 microg/ml of the glucan. The time effect of PCM3-II
      was then investigated by treating the breast cancer cells with 400 microg/ml of
      the glucan for 24, 48 and 72 h, respectively. Results from the flow cytometry
      study demonstrated that PCM3-II induced cell-cycle G1 arrest time-dependently and
      about 90% of the cells in cell cycle were accumulated at G1 phase after 72 h of
      treatment. The G1 arrest was associated with downregulations of the unscheduled
      cyclin D1 and cyclin E expressions in the breast cancer cells. Apoptosis was also
      induced by PCM3-II in the MCF-7 cells, so that the subG1 cells in DNA histogram
      of the flow cytometry were elevated by 5-fold of the control level at 48 h and by
      24-fold at 72 h of treatment. The immunoblot study also showed that the glucan
      induced depletion of the antiapoptotic Bcl-2 protein, but not the proapoptotic
      Bax protein, so that the Bax/Bcl-2 ratio was elevated in the breast cancer cells
      at the time when the most prominent apoptosis was also observed. In conclusion,
      although the detailed mechanism for the anti-tumor activity of the P. cocos beta
      glucan still needs further investigation, this study provides preliminary
      insights into its mode of action and perspectives of its development as a water
      soluble anti-tumor agent.

PMID- 16465425
TI  - Direct activation of the human major vault protein gene by DNA-damaging agents.
AB  - Vaults are barrel-shaped cytoplasmic ribonucleoprotein particles composed of
      three proteins. One of the components, the major vault protein (MVP) initially
      named the lung resistance-related protein (LRP), was found to be overexpressed in
      various multidrug resistant cancer cell lines and clinical samples. In this
      study, we investigated whether anticancer drugs could directly induce MVP protein
      or gene expression in the SW-620 human colorectal cancer cell line, in which MVP
      has been shown to be induced by the differentiation-inducing agent, sodium
      butyrate (NaB). MVP protein levels were enhanced in SW-620 cells after a 72 h
      treatment with doxorubicin (Adr), etoposide (VP-16), cis-platinum (II) diammine
      dichloride (CDDP) or SN-38, but not vincristine (VCR) or paclitaxel (Taxol) at
      their IC50 concentration. Treatment for 48 h with Adr, VP-16 and SN-38 at their
      IC50 concentration also enhanced the expression of MVP mRNA. Moreover, Adr could
      directly enhance the transcriptional activity of MVP promoter regions. On the
      other hand, the Adr treatment did not affect the stability of MVP mRNA.
      Furthermore, MVP levels were also elevated after treatment with the DNA-damaging
      agents, ethidium bromide (EtBr) and ultraviolet light (UV) irradiation. Our
      findings therefore suggest that DNA damage enhances MVP promoter activity. Since
      the MVP protein and mRNA have low turnover rates, a slight enhancement of MVP
      promoter activity could lead to a considerable increase in the level of MVP.

PMID- 16465426
TI  - The association between vascular endothelial growth factor-C, its corresponding
      receptor, VEGFR-3, and prognosis in primary breast cancer: a study with 193
      cases.
AB  - Lymphangiogenesis plays an important role in several normal and pathological
      conditions, such as wound healing, pathogen infection, inflammation or the
      metastasis formation of endothelial malignancies. Vascular endothelial growth
      factor-C (VEGF-C) and VEGF-D are important and specific regulatory factors for
      lymphatic endothelial proliferation and lymphangiogenesis. Both growth factors
      mediate their biological activity mainly by VEGF receptor-3 (VEGFR-3, Flt-4). In
      this study, we measured intratumoral levels of VEGF-C and VEGFR-3 through enzyme
      linked immunosorbent assay (ELISA) in 193 primary breast cancer tissues and
      examined their prognostic values. A significant correlation was found between the
      VEGF-C and VEGFR-3 protein levels. High VEGF-C levels were associated with low
      grade tumors and a smaller size. Univariate analysis showed that high VEGF-C was
      significantly associated with a favourable prognosis for disease-free survival
      (DFS) and overall survival (OS). No significant prognostic value of VEGFR-3 was
      detected. Multivariate analysis confirmed the independent prognostic value of
      VEGF-C. The intratumoral VEGF-C level is a significant prognostic indicator of
      primary breast cancer. An investigation of the mechanisms of VEGF-C protein
      processing in human cancer tissue should be carried out in the future.

PMID- 16465427
TI  - p16 gene alterations in locally advanced squamous cell carcinoma of the head and
      neck.
AB  - We previously documented the presence of mutations/deletions in the tumor
      suppressor gene p16 in squamous cell carcinoma of the head and neck (SCCHN).
      However, the association of these p16 alterations with clinical outcome is
      unknown. In this study, RNA was isolated from 19 frozen SCCHN from 19 patients
      who were previously enrolled in the OSU intensification regimen 2. Quantitative
      real-time RT-PCR and direct sequencing analysis was then performed on the
      specimens to detect p16 gene alterations. Clinical outcome for each patient was
      updated and correlated with the p16 alterations found. Five tumor specimens were
      found to have no or very low expression of p16 when compared with normal tissue.
      The remaining 14 tumor samples demonstrated overexpression of p16 relative to the
      level of expression in normal tissue. Sequence analysis of the p16 RT-PCR product
      from these specimens allowed identification of mutational changes in the coding
      sequence of p16 in four of the SCCHN specimens. Subsequent analysis of clinical
      outcome associated with locoregional/distant failure demonstrated no correlation
      with either altered expression of p16 or mutational status of p16. Results from
      this study indicate that p16 alterations are frequently found in this cohort of
      SCCHN. However, p16 alterations alone do not appear to be associated with
      clinical outcome.

PMID- 16465429
TI  - Astatinated trastuzumab, a putative agent for radionuclide immunotherapy of ErbB2
      expressing tumours.
AB  - The anti-ErbB2 antibody trastuzumab is used for the treatment of patients with
      advanced breast cancer, resulting in a response rate of 40-60%. Coupling with a
      cytotoxic nuclide, e.g. alpha-emitting 211At, may further increase tumour
      response. The tumour-targeting properties of trastuzumab, astatinated using N
      succinimidyl-para-(tri-n-methylstannyl)-benzoate, were evaluated and compared
      with those of radioiodinated trastuzumab in this study. We found that astatinated
      trastuzumab retains high specificity towards ErbB2. While the immunoreactive
      fraction of radioiodinated trastuzumab was higher than that of astatinated
      trastuzumab (76+/-9% versus 54+/-28%), both radioconjugates showed high affinity
      (KD 0.75+/-0.16 nM versus 1.8+/-0.3 nM). A growth inhibition study indicated a
      dose-dependent cell deactivation, in which approximately 74 cell-associated
      astatine decays per cell gave a survival fraction of 4.5+/-0.8x10(-4). Results of
      a comparative animal study on normal mice gave no indication that astatination
      would have any adverse effects on the biodistribution of the antibody. In
      conclusion, the results of the study suggest that astatinated trastuzumab is a
      promising candidate for treating ErbB2-expressing tumours.

PMID- 16465428
TI  - Expression and prognostic roles of PABPC1 in esophageal cancer: correlation with
      tumor progression and postoperative survival.
AB  - The prognosis of patients with esophageal cancer remains poor. TNM classification
      is not sufficient to predict their prognosis, and novel predictive markers of the
      prognosis of esophageal cancer patients are therefore needed. Poly A binding
      protein, cytoplasmic 1 (PABPC1) plays a role in post-transcriptional control of
      mRNA and may be involved in tumorigenesis. PABPC1 expression has not been studied
      in esophageal cancer. Expression of PABPC1 was quantified by real-time reverse
      transcription polymerase chain reaction (RT-PCR) using LightCycler in 41 primary
      esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal
      mucosa. We examined the correlation between PABPC1 expression and the
      clinicopathological factors and prognosis of ESCC patients. Reduced expression of
      PABPC1 was accompanied by locally invasive tumors (t-factor, p=0.0145) and more
      advanced tumors (pathologic stage, p=0.0264). Moreover, ESCC patients with low
      PABPC1 mRNA expression had a significantly shorter postoperative survival time
      than those with high expression (median survival, 3.1 vs. 6.5 months, p=0.002).
      In esophageal cancer, reduced expression of PABPC1 was correlated with local
      tumor progression and poor prognosis after surgery.

PMID- 16465430
TI  - Magnetic resonance angiography without contrast enhancement medium in bone and
      soft tissue tumors.
AB  - The aim of this study was to assess the ability of a new magnetic resonance (MR)
      angiography technique that does not use contrast enhancement medium to depict the
      vascularity of musculoskeletal neoplasms, and evaluate its clinical utility. We
      performed 3D fresh blood imaging (FBI) MR angiography in 57 patients with bone or
      soft tissue tumors, and the detection of vessels in and around the tumor was
      evaluated. Moreover, differences in vascularity between benign and malignant
      tumors were analyzed. In the lower leg, large arteries such as femoral or
      popliteal arteries were visible. In the trunk or arm, large vessels such as
      subclavian or iliac arteries were visible. Discrimination between benign and
      malignant tumors was impossible in bone tumors; however, the mean value of
      vascularity differed between benign and malignant tumors in the soft tissue
      tumors. This is the first trial of the FBI method for bone and soft tissue
      tumors. The still developing method of MRA without contrast materials could
      clearly depict major arteries in the trunk and the extremities, this method may
      replace conventional MRA of bone and soft tissue tumors because it produces vivid
      images while being non-invasive.

PMID- 16465431
TI  - Prospective evaluation of hepatitis B, C and HIV infections as possible sequelae
      of antineoplastic treatment in paediatric sarcoma patients: a report from the
      Late Effects Surveillance System.
AB  - Cancer therapy and supportive measures entail the risk of infection with
      hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV). The
      objective of this analysis was to establish the incidence of infections with
      these viruses during antineoplastic treatment in our paediatric sarcoma patients,
      who are being followed-up within the Late Effects Surveillance System (LESS),
      which prospectively registers sequelae of therapy for Ewing's-, soft tissue- and
      osteosarcoma in patients treated in Germany, Austria and Switzerland within the
      trials EICESS-92/EURO-E.W.I.N.G.-99, CWS-96/CWS-2002P and COSS-96. We studied 264
      eligible relapse-free paediatric patients [median age at diagnosis 14.3 (IQR 11.1
      16.4) years], treated from January 7, 1998 until April 24, 2004. According to the
      LESS protocol, serological examinations for HBV, HCV and HIV were scheduled 4
      weeks and 6 months after cessation of antineoplastic treatment. The median follow
      up was 20.6 (IQR 12.4-26) months. None of the patients was reported to have
      acquired HBV, HCV or HIV during antineoplastic treatment. Blood donor screening
      and prophylactic measures employed in Germany, Austria and Switzerland to prevent
      infections of cancer patients with HBV, HCV and HIV seem to be very effective,
      having fully prevented new infections in this large cohort of paediatric sarcoma
      patients.

PMID- 16465432
TI  - Osteosarcoma: current status of immunotherapy and future trends (Review).
AB  - Osteosarcoma is the most common primary bone tumor and represents a major
      therapeutic challenge in medical oncology. While the use of aggressive
      chemotherapy has drastically improved the prognosis of the patients with non
      metastatic osteosarcomas, the very poor prognosis of patients with metastasis
      have led to the exploration of new, more effective and less toxic treatments,
      such as immunotherapy for curing osteosarcoma. Compared to the numerous reports
      describing successful immunotherapy for other solid tumors, the number of reports
      concerning immunotherapy for osteosarcoma is low. However, this therapeutic
      strategy opens new areas for the treatment of osteosarcoma. In this review, the
      reasons for delay and all elements essential to develop immunotherapy concerning
      osteosarcoma are defined. Several pieces of evidence strongly support the
      potential capability of new therapies such as cellular therapy and gene therapy
      to eradicate osteosarcoma. Thus, clinical human trials using peptides, cytokines
      and dendritic cells have been performed. Tumor-infiltrating lymphocytes and some
      tumor antigens have been identified in osteosarcoma and resulted in an important
      breakthrough in cellular immunotherapy. Also, RANKL/RANK/OPG, the key regulator
      of bone metabolism, is a hot spot in this field as therapeutic tools.
      Immunotherapy for osteosarcomas has great potential, promising improvement in the
      survival rate and better quality of life for the patients.

PMID- 16465433
TI  - Redundant expression of canonical Wnt ligands in human breast cancer cell lines.
AB  - Human breast cancer displays nuclear accumulation of beta-catenin and induction
      of cyclin D1 expression, which suggests that canonical Wnt/beta-catenin signaling
      is activated. In other cancers, the activation of canonical wnt/beta-catenin
      signaling is associated with APC, CTNNB1 or AXIN1 mutations. However, these
      mutations are rare or absent in breast cancer. In search of alternative
      mechanisms, we performed comprehensive expression analysis of Wnt signaling
      molecules, including 19 Wnt ligands, ten Frizzled receptors, two co-receptors and
      four Lef/TCF transcription factors in immortalized normal human mammary
      epithelial cells (HMEC) and six breast cancer cell lines. HMEC expressed all
      Frizzled receptors except FZD9 and FZD10. They also expressed LRP5 and LRP6 co
      receptors, as well as four Lef/TCF transcription factors. HMEC cells also
      expressed many Wnt ligands, including WNT1, WNT2B, WNT3, WNT5A, WNT5B, WNT7B,
      WNT9A, WNT10B and WNT16. Redundant expression of Wnt ligands, Frizzled receptors,
      co-receptors and Lef/TCF transcription factors was maintained in breast cancer
      cell lines with some exceptions. The most important changes in cancer cell lines
      concerned Wnt ligand expression. We noticed that most breast cancer cell lines
      overexpressed WNT3A, WNT4, WNT6, WNT8B, WNT9A and WNT10B. In contrast, the
      expression of WNT5A, WNT5B and WNT16 was usually down-regulated. It is noteworthy
      that all six Wnt ligands that are overexpressed in malignant cell lines are known
      to signal through the canonical Wnt/beta-catenin signaling pathway, whereas down
      regulated WNT5A and WNT5B ligands signal via the non-canonical pathway. The
      expression of both canonical Wnt ligands and most Frizzled receptors in breast
      cancer cell lines suggests that canonical Wnt/beta-catenin signaling is activated
      in these cell lines by an autocrine/paracrine mechanism. In support of this
      prediction, we observed nuclear beta-catenin accumulation and cyclin D1 induction
      in breast cancer cell lines, but not in HMEC. These results imply that ligand
      dependent canonical Wnt/beta-catenin signaling is active in human breast cancer.

PMID- 16465434
TI  - Cytokine-dependent invasiveness in B16 murine melanoma cells: role of uPA system
      and MMP-9.
AB  - Proteases are crucial for the spread of cancer cells from a primary tumor to the
      site of secondary growth. This study examined the ability of IFNgamma and
      TNFalpha to stimulate a better invasiveness in B16 murine melanoma cells, and
      investigated whether this enhanced ability was related to a higher expression of
      protease activities, such as urokinase plasminogen activator (uPA) and its
      receptor (uPAR), and matrix metalloproteinases 2 and 9 (MMP-2, MMP-9). We found
      that murine melanoma cells enhanced their lung-colonizing potential in vivo and
      invasiveness through Matrigel-coated filters upon costimulation with IFNgamma and
      TNFalpha; neither IFNgamma nor TNFalpha alone, at the dose used in the
      experiments, was able to elicit a change in the invasive/metastatic efficiency of
      melanoma cells. The invasive phenotype of murine melanoma cells stimulated with
      IFNgamma and TNFalpha was characterized by an enhanced uPA/uPAR and MMP-9
      expression: TNFalpha promoted MMP-9 mRNA expression and pro-MMP-9 protein
      secretion, and the costimulation with IFNgamma and TNFalpha was required to
      potentiate the expression of mRNA and protein for uPAR, and to induce a
      redistribution of uPA from the soluble to the cell body-associated form. Both
      monoclonal antibodies, anti-uPAR and anti-MMP-9, caused a significant reduction
      of invasiveness in IFNgamma/TNFalpha-stimulated melanoma cells. These results
      indicate that invasiveness in B16 murine melanoma cells can be regulated in a
      cytokine-specific fashion and is dependent on the synergism between the uPA/uPAR
      system and MMP-9.

PMID- 16465435
TI  - Gadolinium enhances the sensitivity of SW-1573 cells for thermal neutron
      irradiation.
AB  - Gadolinium neutron capture therapy (Gd-NCT) is an experimental cancer treatment
      based on the physical principal that neutron capture by gadolinium-157 ensures
      the release of focal high-dose radiation, such as gamma-rays and electrons.
      Survival and induction of chromosomal aberrations of human SW-1573 cells was
      studied after thermal neutron irradiation without and with gadolinium. After
      neutron irradiation with Gd-DTPA, an alpha-enhancement factor of 2.3 was obtained
      compared to thermal neutron irradiation alone. Gd-DTPA could not radioenhance the
      cells for gamma-ray irradiation. Induction of colour junctions and chromosome
      fragments by thermal neutron irradiation and Gd-NCT were studied using PCC-FISH.
      Correlations (r2-value) between survival and chromosome aberrations ranged from
      0.81 to 0.94 for colour junctions and from 0.78 to 0.98 for chromosome fragments
      of chromosomes 18 and 2 respectively. Thermal neutron irradiation with or without
      gadolinium induced more chromosome aberrations than gamma-ray irradiation. After
      correction for chromosome length it appeared that both chromosomes were equally
      sensitive to radiation. It is concluded that Gd-NCT at a non-toxic concentration
      of gadolinium is effective in inducing cell death and chromosome aberrations in
      in vitro cell cultures.

PMID- 16465436
TI  - Ionizing radiation synergistic induction of cyclooxygenase-2 with benzo[a]pyrene
      diol-epoxide through nuclear factor of activated T cells in mouse epidermal Cl 41
      cells.
AB  - Carcinogenic effects of ionizing radiation and benzo[a]pyrene-7,8-diol-9,10
      epoxide (B[a]PDE), a major metabolite of benzo[a]pyrene (B[a]P), have been well
      demonstrated both in vitro and in vivo. Two-stage carcinogenesis results indicate
      that mouse skin is highly susceptible to both ionizing radiation and
      benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), a major metabolite of
      benzo[a]pyrene (B[a]P). It is believed that signaling pathways leading to the
      regulation of gene expression play a significant role in the development of skin
      cancers. The NFAT family of proteins are important transcription factors involved
      in the regulation of various target genes, such as IL-1 and TNF-alpha, which play
      key roles in the regulation of inflammation and carcinogenesis. Thus, the effect
      of ionizing radiation and B[a]PDE on COX-2 induction and NFAT3 activation, and
      their relationship, was investigated in mouse epidermal Cl 41 cells. We found
      that B[a]PDE exposure induced a very high level of NFAT activation in mouse
      epidermal Cl 41 cells. Ionizing radiation exhibited a synergistic effect with
      B[a]PDE on NFAT activation and COX-2 induction, while ionizing radiation alone
      had no effect. By stably knocking down NFAT3 protein expression by means of the
      specific interfering RNA (siRNA) technique, we found that COX-2 induction by
      B[a]PDE and the synergistic effect of ionizing radiation with B[a]PDE was totally
      blocked. These results indicate that ionizing radiation acts synergistically with
      B[a]PDE on COX-2 induction, and the synergism is dependent on the NFAT3 pathway.

PMID- 16465437
TI  - Radiation dose to testes and risk of infertility from radiotherapy for rectal
      cancer.
AB  - This study aims to provide the means for testicular dose estimation from
      radiotherapy for rectal cancer. Rectal irradiation was simulated on a humanoid
      phantom using a 6 MV photon beam. The effect of field size, distance from
      irradiated area, wedge introduction into lateral beams, tissue thickness along
      the beam axis and use of gonad shields on the testicular dose was examined.
      Testicular dose was measured in five patients undergoing radiotherapy for rectal
      carcinoma. For a 4500 cGy tumour dose, testicular dose was 32-216 cGy depending
      upon the field dimensions and the distance from the field isocenter. The presence
      of wedges increased the testicular dose by a factor up to 2.2. The increase of
      irradiated tissue thickness increased the gonadal dose up to 40% whereas the use
      of the appropriate gonad shield reduced the dose by >66%. A simple method was
      developed to estimate testicular dose. The mean difference between the in vivo
      gonadal doses and the doses calculated using the proposed method was 5.8%.
      Testicular dose can exceed the value of 100 cGy, which permits a complete
      recovery of spermatogenesis. The presented data can be used to estimate the
      gonadal dose and the associated risk of infertility attributable to rectal
      irradiation.

PMID- 16465438
TI  - Intracellular localization of matrix metalloproteinases and their inhibitors in
      cultured tumor cell lines: flow cytometric analysis.
AB  - Coordinate cell-surface expression of matrix metalloproteinases (MMPs) and their
      inhibitors (TIMPs) on cancer cells, tumor-infiltrating lymphocytes (TIL) and
      cancer-associated myofibroblasts has been shown to play an important role in
      tumor invasion and metastasis in organ tissues. However, precise localization of
      tumor cell lines in vitro has remained obscure. The aim of this study was to
      investigate the spatial localization of these proteolytic enzymes in 21 tumor
      cell lines consisting of 8 gastric, 4 pancreatic, 2 gallbladder, 1 extrahepatic
      bile duct cancer and 6 T- or B-cell tumors. The cell-surface and/or intracellular
      localization of MMP-2, -7, and -9, membrane type-1 (MT1)-MMP and TIMP-2 and -4
      was quantitatively determined by flow cytometry in living (non-permeabilized) and
      permeabilized tumor cell lines. As a result, all of the tumor cell lines showed a
      high level of intracellular expression, but a low or undetectable level of cell
      surface expression of MMPs and TIMPs. The findings revealed that intracellular
      MMPs and TIMPs in tumor cell lines were preserved as latent pro-enzymes.

PMID- 16465439
TI  - Puzzling over orphan enzymes.
AB  - Despite the current availability of several hundreds of thousands of amino acid
      sequences, more than 39% of the well-defined enzyme activities (EC numbers) are
      not associated with any sequence in major public databases. This wide gap
      separating knowledge of biochemical function and sequence information is found in
      nearly all classes of enzymes. Thus, there is an urgent need to explore the 1525
      orphan enzymes (EC numbers without associated sequences), in order to
      progressively bridge this unwanted gap. Improving genome annotation could unveil
      a significant proportion of sequenceless enzymes. Peptide mass mapping and
      further genome mining would be useful to identify proper sequence for enzymes
      found in species for which genetic tools are missing. Finally, the whole
      community must help major public databases to begin addressing the problem of
      missing or incomplete information.

PMID- 16465440
TI  - Protein kinases controlling the onset of mitosis.
AB  - This review article focuses on protein kinases regulating the onset and
      transition through mitosis. The essay begins by introducing the structural
      features of the protein kinase catalytic domain and emphasizing the mechanism of
      enzymatic activation of this class of proteins. Next follows a short historical
      perspective on cell division and a description of our current understanding of
      mitosis. In the central part of the review I examine the four major kinases that
      set the stage for mitosis, which consist of Cdk1, Polo-like 1, Nek2 and Aurora
      kinases. For each entry dealt with, I focus particularly on studies that have
      linked DNA damage response pathways to inhibition of kinase activity, and I
      evaluate the conclusions drawn. Finally, I examine protein kinases initially
      described in the context of different cell cycle transitions and only later
      proposed to be involved in the control of mitosis.

PMID- 16465441
TI  - Flavodoxins: sequence, folding, binding, function and beyond.
AB  - Flavodoxins are electron-transfer proteins involved in a variety of
      photosynthetic and non-photosynthetic reactions in bacteria, whereas, in
      eukaryotes, a descendant of the flavodoxin gene helps build multidomain proteins.
      The redox activity of flavodoxin derives from its bound flavin mononucleotide
      cofactor (FMN), whose intrinsic properties are profoundly modified by the host
      apoprotein. This review covers the very exciting last decade of flavodoxin
      research, in which the folding pathway, the structure and stability of the
      apoprotein, the mechanism of FMN recognition, the interactions that stabilize the
      functional complex and tailor the redox potentials, and many details of the
      binding and electron transfer to partner proteins have been revealed. The next
      decade should witness an even deeper understanding of the flavodoxin molecule and
      a greater comprehension of its many physiological roles. The fact that flavodoxin
      is essential for the survival of some human pathogens could make it a drug target
      on its own.

PMID- 16465442
TI  - Nodal signals pattern vertebrate embryos.
AB  - Vertebrate embryonic patterning requires several conserved inductive signals
      including Nodal, Bmp, Wnt and Fgf signals. Nodal, which is a member of the
      transforming growth factor beta (TGFbeta) superfamily, activates a signal
      transduction pathway that is similar to that of other TGFbeta members. Nodal
      genes, which have been identified in numerous vertebrate species, are expressed
      in specific cell types and tissues during embryonic development. Nodal signal
      transduction has been shown to play a pivotal role in inducing and patterning
      mesoderm and endoderm, and in regulating neurogenesis and left-right axis
      asymmetry. Antagonists, which act at different steps in the Nodal signal
      transduction pathway, have been shown to tightly modulate the inductive activity
      of Nodal.

PMID- 16465443
TI  - Retinoblastoma family proteins: insights gained through genetic manipulation of
      mice.
AB  - The retinoblastoma (Rb) gene was identified as the first tumor suppressor gene
      two decades ago. Since this initial discovery, it has become clear that
      deregulated Rb function constitutes a hallmark of human malignancies. Rb is a
      well-established regulator of the cell cycle. Rb has also been implicated in
      playing a role in a wide variety of cellular processes including DNA repair,
      cellular senescence, cell fate determination and apoptosis. Animals lacking Rb
      and/or its family members p107 and p130 have led scientists to uncover new and
      exciting roles for this protein family in development as well as tumor
      suppression. The ability to ablate Rb in a temporal and cell-type-specific manner
      has offered further, often unexpected, insights into Rb function. This review
      summarizes the phenotypic consequences of Rb family ablation in mice, and
      discusses how these findings contribute to the increasingly complex picture of Rb
      family function in development and tumor suppression.

PMID- 16465444
TI  - The macromolecular peptide-loading complex in MHC class I-dependent antigen
      presentation.
AB  - A challenging task for the adaptive immune system of vertebrates is to identify
      and eliminate intracellular antigens. Therefore a highly specialized antigen
      presentation machinery has evolved to display fragments of newly synthesized
      proteins to effector cells of the immune system at the cell surface. After
      proteasomal degradation of unwanted proteins or defective ribosome products,
      resulting peptides are translocated into the endoplasmic reticulum by the
      transporter associated with antigen processing and loaded onto major
      histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are
      transported via the secretory pathway to the cell surface where they are then
      inspected by cytotoxic T lymphocytes, which can trigger an immune response. This
      review summarizes the current view of the intracellular machinery of antigen
      processing and of viral immune escape mechanisms to circumvent destruction by the
      host.

PMID- 16465445
TI  - RNA editing in plant organelles: machinery, physiological function and evolution.
AB  - In plants, RNA editing is a process for converting a specific nucleotide of RNA
      from C to U and less frequently from U to C in mitochondria and plastids. To
      specify the site of editing, the cis-element adjacent to the editing site
      functions as a binding site for the trans-acting factor. Genetic approaches using
      Arabidopsis thaliana have clarified that a member of the protein family with
      pentatricopeptide repeat (PPR) motifs is essential for RNA editing to generate a
      translational initiation codon of the chloroplast ndhD gene. The PPR motif is a
      highly degenerate unit of 35 amino acids and appears as tandem repeats in
      proteins that are involved in RNA maturation steps in mitochondria and plastids.
      The Arabidopsis genome encodes approximately 450 members of the PPR family, some
      of which possibly function as trans-acting factors binding the cis-elements of
      the RNA editing sites to facilitate access of an unidentified RNA editing enzyme.
      Based on this breakthrough in the research on plant RNA editing, I would like to
      discuss the possible steps of co-evolution of RNA editing events and PPR
      proteins.

PMID- 16465446
TI  - The urokinase receptor: a ligand or a receptor? Story of a sociable molecule.
AB  - In this last decade, the structure and functions of the receptor for the
      urokinase-type plasminogen activator have been extensively studied and
      characterized. This interesting receptor plays a key role in cell adhesion,
      migration and proliferation. It was identified 20 years ago as the specific cell
      surface molecule that could bind and concentrate urokinase on the cell membrane,
      thus initiating the proteolytic cascade promoted by the activation of
      plasminogen. The identification of new extracellular ligands, such as
      vitronectin, and of cell-surface interactors, such as integrins and fMet-Leu-Phe
      receptors, shed new light on its possible roles, totally independent of the
      enzymatic properties of its ligand. uPAR ligands and interactors and the
      functional consequences of the multiple binding capability of this intriguing
      receptor are reviewed here.

PMID- 16465448
TI  - Pre-messenger RNA processing and its regulation: a genomic perspective.
AB  - The sequence of entire genomes from higher eukaryotes revealed that an average
      gene is very large due to the interruption of the coding sequence with large
      noncoding introns. Introns are co-transcriptionally removed by splicing with
      great accuracy and fidelity, although contrary to our expectations, currently
      known signals required for pre-messenger RNA (mRNA) processing are very
      degenerate and redundant. Furthermore, the vast majority of genes are
      alternatively processed. A large number of proteins are therefore involved in
      generating specificity in pre-mRNA processing that requires a dedicated
      mechanisms to operate at genomic dimensions. In this review I will summarize
      recent progress in understanding how established principles of pre-mRNA
      processing extend to genomic dimensions and discuss emerging concepts in coupling
      of pre-mRNA processing with other nuclear events and nuclear organization.

PMID- 16465449
TI  - Hedgehog signaling in pancreas development and disease.
AB  - Since its discovery, numerous studies have shown that the Hedgehog (Hh) signaling
      pathway plays an instrumental role during diverse processes of cell
      differentiation and organ development. More recently, it has become evident that
      Hh signaling is not restricted to developmental events, but retains some of its
      activity during adult life. In mature tissues, Hh signaling has been implicated
      in the maintenance of stem cell niches in the brain, renewal of the gut
      epithelium and differentiation of hematopoietic cells. In addition to the basal
      function in adult tissue, deregulated signaling has been implicated in a variety
      of cancers, including basal cell carcinoma, glioma and small cell lung cancer.
      Here, we will focus on the role of Hh signaling in pancreas development and
      pancreatic diseases, including diabetes mellitus, chronic pancreatitis and
      pancreatic cancer.

PMID- 16465450
TI  - Cellular regulation and molecular interactions of the ferritins.
AB  - Controlling iron/oxygen chemistry in biology depends on multiple genes,
      regulatory messenger RNA (mRNA) structures, signaling pathways and protein
      catalysts. Ferritin, a protein nanocage around an iron/oxy mineral, centralizes
      the control. Complementary DNA (antioxidant responsive element/Maf recognition
      element) and mRNA (iron responsive element) responses regulate ferritin synthesis
      rates. Multiple iron-protein interactions control iron and oxygen substrate
      movement through the protein cage, from dynamic gated pores to catalytic sites
      related to di-iron oxygenase cofactor sites. Maxi-ferritins concentrate iron for
      the bio-synthesis of iron/heme proteins, trapping oxygen; bacterial mini
      ferritins, DNA protection during starvation proteins, reverse the substrate
      roles, destroying oxidants, trapping iron and protecting DNA. Ferritin is
      nature's unique and conserved approach to controlled, safe use of iron and
      oxygen, with protein synthesis in animals adjusted by dual, genetic DNA and mRNA
      sequences that selectively respond to iron or oxidant signals and link ferritin
      to proteins of iron, oxygen and antioxidant metabolism.

PMID- 16465451
TI  - Neuroserpin: a serpin to think about.
AB  - Proteinases and their inhibitors play important roles in neural development,
      homeostasis and disease. Neuroserpin is a member of the serine proteinase
      inhibitor (serpin) superfamily that is secreted from the growth cones of neurons
      and inhibits the enzyme tissue-type plasminogen activator (tPA). The temporal and
      spatial pattern of neuroserpin expression suggests a role in synaptogenesis and
      is most prominent in areas of the brain that participate in learning, memory and
      behaviour. Neuroserpin also provides neuronal protection in pathologies such as
      cerebral ischaemia and epilepsy by preventing excessive activity of tPA. Point
      mutations in neuroserpin cause aberrant conformational transitions and the
      formation of loop-sheet polymers that are retained within the endoplasmic
      reticulum of neurons, forming inclusion bodies that underlie an autosomal
      dominant dementia that we have called familial encephalopathy with neuroserpin
      inclusion bodies or FENIB. We review here the role of neuroserpin and other
      proteinase inhibitors in brain development, function and disease.

PMID- 16465447
TI  - The role of VEGF receptors in angiogenesis; complex partnerships.
AB  - Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel
      development and homeostasis but also have profound effects on neural cells. VEGFs
      are predominantly produced by endothelial, hematopoietic and stromal cells in
      response to hypoxia and upon stimulation with growth factors such as transforming
      growth factors, interleukins or platelet-derived growth factor. VEGFs bind to
      three variants of type III receptor tyrosine kinases, VEGF receptor 1, 2 and 3.
      Each VEGF isoform binds to a particular subset of these receptors giving rise to
      the formation of receptor homo- and heterodimers that activate discrete signaling
      pathways. Signal specificity of VEGF receptors is further modulated upon
      recruitment of coreceptors, such as neuropilins, heparan sulfate, integrins or
      cadherins. Here we summarize the knowledge accumulated since the discovery of
      these proteins more than 20 years ago with the emphasis on the signaling pathways
      activated by VEGF receptors in endothelial cells during cell migration, growth
      and differentiation.

PMID- 16465453
TI  - Effect of ABA upon anthocyanin synthesis in regenerated torenia shoots.
AB  - To elucidate the mechanism of anthocyanin synthesis induction concomitant with
      chlorophyll degradation, we established a system in which anthocyanin synthesis
      and degradation of chlorophyll in regenerated torenia (Torenia fournieri) shoots
      was induced on medium containing 7% sucrose. Here, we studied the effect of
      several plant-growth regulators on anthocyanin synthesis and the degradation of
      chlorophyll in the torenia shoot regenerating system. Exogenous abscisic acid
      (ABA) could induce anthocyanin synthesis and chlorophyll senescence in
      regenerating torenia shoots on the medium containing a low concentration of
      sucrose (1.5%). We determined the changes in the amount of endogenous ABA in the
      regenerated shoots during the process of anthocyanin synthesis on the medium
      containing 7% sucrose. It was revealed that the 7% sucrose treatment elevated
      endogenous ABA levels before the induction of anthocyanin synthesis and
      chlorophyll degradation. However, while retransfer to the 1.5% sucrose medium
      resulted in a gradual decrease in the ABA level and a failure of induction of
      anthocyanin synthesis, normal shoot regeneration. These results suggest that
      changes in the amount of endogenous ABA may play an important role in the
      induction of anthocyanin synthesis and chlorophyll degradation in regenerated
      torenia shoots.

PMID- 16465452
TI  - Vertical distribution and diversity of bacteria and archaea in sulfide and
      methane-rich cold seep sediments located at the base of the Florida Escarpment.
AB  - The bacterial and archaeal communities of the sediments at the base of the
      Florida Escarpment (Gulf of Mexico, USA) were investigated using molecular
      phylogenetic analysis. The total microbial community DNA of each of three
      vertical zones (top, middle and bottom) of a sediment core was extracted and the
      16S rRNA genes were amplified by PCR, cloned and sequenced. Shannon-Weaver
      Diversity measures of bacteria were high in all three zones. For the archaea,
      diversity was generally low, but increased with depth. The archaeal clonal
      libraries were dominated by representatives of four groups of organisms involved
      in the anaerobic oxidation of methane (ANME groups). Phylogenetic analysis of
      bacteria suggests the dominance of epsilon-proteobacteria in the top zone, the
      epsilon-, delta- and gamma-proteobacteria in the middle zone and the delta
      proteobacteria in the bottom zone of the core. Members of the Cytophaga
      Flexibacter-Bacteroidetes group, the Chloroflexi/green non-sulfur bacteria, the
      Gram+ (Firmicutes), the Planctomyces, candidate division WS3 and Fusobacterium
      were also detected. Our data suggest that the community structure and diversity
      of microorganisms can shift greatly within small vertical distances, possibly in
      response to changes in the physical and chemical conditions.

PMID- 16465455
TI  - Effects of stimulus-response compatibility in Parkinson's disease: a
      psychophysiological analysis.
AB  - The present study investigated the mechanisms underlying stimulus-response
      compatibility effects in Parkinson's disease patients and matched controls. Since
      basal ganglia are involved in the selection and inhibition of competing responses
      we examined whether basal ganglia dysfunction in Parkinson's disease leads to
      greater interference effects compared to the control subjects. Reaction times and
      lateralized movement-related cortical potentials (lateralized readiness
      potential: LRP) were recorded in two modified Eriksen flanker tasks. Both groups
      were influenced by compatibility conditions; interference was seen as enhanced
      reaction time and error rate, as well as incorrect early LRP and delayed late LRP
      in incongruent trials. Altogether, behavioral and electrophysiological measures
      showed the interference to be rather smaller for the patients than for the
      controls. In contrast, facilitation did not differ among groups. Hence the claim
      that Parkinson's disease patients are more influenced than controls by
      interfering directional stimuli appears not always valid.

PMID- 16465454
TI  - Chronic neuroleptic treatment reduces endogenous kynurenic acid levels in rat
      brain.
AB  - The brain and cerebrospinal fluid levels of kynurenic acid (KYNA), a metabolite
      of the kynurenine pathway of tryptophan degradation and antagonist of the
      glycine(B) receptor and the alpha7 nicotinic acetylcholine receptor, are elevated
      in persons with schizophrenia. To evaluate whether this increase is related to
      antipsychotic medication, we examined the effects of haloperidol (HAL), clozapine
      (CLOZ) or raclopride (RAC) on brain KYNA levels in rats. Animals received either
      acute drug injections or ingested the drugs chronically with the drinking water.
      Acute application or one-week drug exposure had no effect on brain KYNA levels.
      After one month, HAL, CLOZ and RAC all caused significant reductions in KYNA
      levels in striatum, hippocampus and frontal cortex. Quantitatively similar
      reductions in the brain tissue content of KYNA were observed after one year of
      HAL administration. All these effects were accompanied by equivalent decreases in
      the extracellular concentration of KYNA, measured by striatal microdialysis.
      Separate animals received an intrastriatal infusion of (3)H-kynurenine to probe
      the entire kynurenine pathway acutely in rats treated with HAL for one year.
      These animals showed reduced (3)H-KYNA production, but no changes in the
      formation of other kynurenine pathway metabolites. By enhancing glutamatergic and
      cholinergic neurotransmission, reduced brain KYNA levels may play a role in the
      clinical effects of prolonged antipsychotic medication.

PMID- 16465456
TI  - Imaging of serotonin transporters and its blockade by citalopram in patients with
      major depression using a novel SPECT ligand [123I]-ADAM.
AB  - We studied the midbrain SERT availability in patients with major depression and
      assessed the relation of SERT occupancy by citalopram to the treatment response.
      21 non-medicated patients with major depression and 13 healthy controls were
      examined by [(123)I]-ADAM SPECT. The midbrain SERT availability (SERT V(3)'') was
      calculated using individual MRI scans. In 13/21 patients SPECT was repeated 7
      days after oral medication with citalopram (10 mg/day). We found no significant
      difference in the mean midbrain SERT availability between the studied patients
      with major depression and healthy controls (0.86 +/- 0.27 vs. 0.71 +/- 0.44, p =
      0.069). The mean SERT occupancy accounted to 61%. The degree of SERT blockade by
      citalopram did not correlate with the reduction in HAMD total score. Treatment
      with low-dosed citalopram caused individually variable occupancy of the midbrain
      SERT and a rapid clinical improvement in 54% of the investigated patients.

PMID- 16465457
TI  - Dendritic excrescences seem to characterize hippocampal CA3 pyramidal neurons in
      humans.
AB  - Excrescences are unique dendritic postsynaptic structures of the hippocampal
      formation. Only CA3 pyramidal neurones and hilar mossy cells possess these
      complex dendritic structures. Dendritic excrescences have so far only been
      investigated in rabbit, rat and rhesus monkey. Applying a Golgi impregnation
      method optimized for human brain tissue, we describe the detailed morphology of
      excrescences of CA3 pyramidal neurons of man. Human thorny excrescences possess a
      thin and single spine neck and multiple spine heads (4 on average, sometimes more
      than 10). Human cluster excrescences sit upon the dendrite with a broad stem, and
      exhibit a "papilloma-like" surface. Some human CA3 pyramidal neurons seem to
      possess markedly longer spine necks and larger spine heads compared to human
      neocortical pyramid cells; they were named long-neck spines. Thorny excrescences,
      cluster excrescences and the newly described long-neck spines can also be found
      on the dendritic main stem of human CA3 pyramidal neurons.CA2 pyramidal neurons
      neither possess these long neck spines nor thorny or cluster excrescences. Thus,
      the unique excrescences of CA3 pyramidal neurones seem to be another criterion
      for a demarcation between the CA3- and CA2 region of the human hippocampus.

PMID- 16465458
TI  - The plasma alpha-synuclein levels in patients with Parkinson's disease and
      multiple system atrophy.
AB  - alpha-Synuclein, a synaptic protein of unknown function, is a major component of
      Lewy bodies and may play a role in the pathophysiological process of Parkinson's
      disease (PD). In this study, we measured the plasma alpha-synuclein levels in 105
      patients with PD, 38 patients with multiple system atrophy (MSA), and 51 age
      matched controls. The alpha-synuclein level was significantly elevated in
      patients with PD (79.9 +/- 4.0 pg/ml, p < 0.001) and in those with MSA (78.1 +/-
      3.5 pg/ml, p = 0.019) compared with the level in controls (76.1 +/- 3.9 pg/ml).
      The alpha-synuclein level was higher in patients with PD than in those with MSA
      (79.9 +/- 4.0 vs 78.1 +/- 3.5, p = 0.016). Our study demonstrated that the alpha
      synuclein level in plasma is elevated in patients with PD and MSA.

PMID- 16465459
TI  - Inverse relationship between central serotonergic neurotransmission and blood
      pressure in alcohol-dependent male subjects.
AB  - Data has accumulated indicating an inverse relation between central serotonergic
      (5-HT) neurotransmission and blood pressure in hypertensive rats and in healthy
      individuals. The present study aimed to elucidate whether an inverse relation
      exists between systolic (SBP) and diastolic (DBP) blood pressure levels and
      central 5-HT neurotransmission also in a group of alcohol-dependent individuals.
      Central 5-HT neurotransmission was assessed by using the maximum prolactin (PRL)
      responses to the 5-HT probe DL-fenfluramine (DL-FEN; 60 mg po) in 17 alcohol
      dependent male subjects investigated during a period of on-going alcohol intake.
      BP was measured immediately before all time points for blood sampling, and
      readings before DL-FEN administration were used as the subjects resting BP.
      Results showed that there were inverse correlations between the maximum PRL
      responses to DL-FEN and the SBP levels (r = -0.57, p < 0.002) and with the DBP
      levels (r = -0.52, p < 0.05), respectively. The present study suggests the
      existence of an association between central 5-HT neurotransmission and blood
      pressure regulation also in alcohol-dependent individuals.

PMID- 16465460
TI  - Microarray analysis reveals distinct gene expression patterns in the mouse cortex
      following chronic neuroleptic and stimulant treatment: implications for body
      weight changes.
AB  - Atypical neuroleptics are associated with clinical significant weight gain,
      whereas stimulants are used as anorexiant drugs. The aim of this study was to
      examine gene expression changes in the mouse frontal cortex following chronic
      oral treatment with antipsychotics and a stimulant by microarray assessments.
      Twenty 10-12-week-old male C57BL6 mice received daily for 31 days either the
      typical neuroleptic haloperidol (1 mg/kg), the atypical neuroleptic clozapine (10
      mg/kg) or the stimulant phenylpropanolamine (3 mg/kg). We identified a set of
      genes that was differently expressed between the neuroleptic-treated groups and
      the stimulant-treated group. Importantly, we found in the majority of gene
      alterations down-regulation in genes involved in ATP biosynthesis and lipid
      metabolism following the stimulant treatment, suggesting these genes as
      candidates that may regulate body weight. We also identified remarkable
      expression patterns of genes that encode signalling molecules (e.g. insulin,
      mitochondrial uncoupling protein 1) that are implicated in the control of food
      intake and are differently expressed in the neuroleptic groups.

PMID- 16465461
TI  - Apolipoprotein E, angiotensin-converting enzyme and kallikrein gene polymorphisms
      and the risk of Alzheimer's disease and vascular dementia.
AB  - Lipoproteins and vascular factors may play roles in the development of
      Alzheimer's disease (AD) and/or vascular dementia (VaD). In this study, odd
      ratios (ORs) and 95% confidence intervals (CIs) for apolipoprotein E (APOE),
      angiotensin-converting enzyme (ACE), and kallikrein (KLK1) polymorphisms were
      computed to test their association with the disease by a case-control study. The
      risk of AD was significantly increased for individuals with APOE varepsilon4
      allele (OR = 3.73, 95% CI = 2.38-5.98). The risk of AD was also significant for
      people with ACE DD genotype, D allele, or T-D haplotype [OR (95% CI) = 4.29 (1.96
      10.23), 1.90 (1.35-2.70), or 2.91 (1.71-5.10), respectively]. The above
      association between ACE-VaD was also strong (p = 0.0012, 0.0050, 0.0007,
      respectively). Reporter constructs containing the -240 A or T allele displayed
      similar transcriptional activity in both HEK-293 and IMR-32 cells. Thus, another
      putative pathogenic marker that is linked with the Alu D allele might affect the
      risk of AD and VaD in Taiwan.

PMID- 16465462
TI  - Kynurenic acid synthesis in bovine retinal slices--effect of glutamate agonists.
AB  - The purpose of the present study was to investigate the effect of glutamate
      agonists upon kynurenic acid (KYNA) production in bovine retinal slices.
      Quantitative analysis of newly synthesized KYNA was carried out using an HPLC
      system and detected fluorimetrically. Glutamate at the concentration of 0.01, 0.1
      and 1 mM reduced KYNA synthesis in the retinal slices to 70% (p < 0.05), 35% (p <
      0.01) and 23% (p < 0.001), respectively. The concentration of glutamate reducing
      production of KYNA by 50% (IC(50)) was 0.035 mM (0.02-0.06). Aspartate at the
      concentration of 0.01, 0.1 and 1 mM lowered KYNA synthesis in the retinal slices
      to 80% (p < 0.01), 57% (p < 0.001) and 43% (p < 0.001), respectively. In
      contrast, kainic acid (up to 5 mM), alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA) (up to 1 mM) and 1-aminocyclopentane-trans-1,3
      dicarboxylic acid (t-ACPD) (up to 3 mM) turned out to be ineffective in
      diminishing KYNA synthesis. These data demonstrate that glutamate, aspartate and
      N-methyl-D-aspartate (NMDA) inhibit KYNA synthesis in bovine retinal slices with
      different potency.

PMID- 16465463
TI  - Potentiating effects of L-type Ca(2+) channel blockers on pentobarbital-induced
      hypnosis are influenced by serotonergic system.
AB  - In order to elucidate the mechanism(s) behind the interactions between
      barbiturates and Ca(2+) antagonists, the effects of three structurally diverse
      types of Ca(2+) antagonists combined or not with 5-HT on pentobarbital-induced
      hypnosis in mice were investigated. The results showed that dihydropyridine
      derivative nifedipine (10.0 and 20.0 mg/kg, p.o.) and other types of Ca(2+)
      antagonist, verapamil (5.0 and 10.0 mg/kg, p.o.) and diltiazem (2.5, 5.0 and 10.0
      mg/kg, p.o.) increased both the sleeping time in hypnotic dosage of pentobarbital
      (45 mg/kg, i.p.) treated mice and the rate of sleep onset in the sub-hypnotic
      dosage of pentobarbital (28 mg/kg, i.p.) treated mice in a dose-dependent manner,
      respectively, and these effects were significantly augmented by 5
      hydroxytryptophan (5-HTP), the immediate precursor of 5-hydroxytryptamine (5-HT).
      Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of
      tryptophan hydroxylase, significantly decreased pentobarbital-induced sleeping
      time and nifedipine (10.0 mg/kg, p.o.), verapamil (5.0 mg/kg, p.o.) and diltiazem
      (2.5 mg/kg, p.o.) abolished this effect. From these results, it should be
      presumed that the augmentative effect of L-type Ca(2+) channel blockers on
      pentobarbital-induced sleep may be influenced by serotonergic system.

PMID- 16465464
TI  - A transitory activation of protein kinase-A induces a sustained tau
      hyperphosphorylation at multiple sites in N2a cells-imply a new mechanism in
      Alzheimer pathology.
AB  - Overactivation of protein kinase in the end stage of Alzheimer's disease brain
      has not been established. The purpose of the present study was to explore the
      possible mechanism for protein kinases in leading to Alzheimer-like tau
      hyperphosphorylation. We found that incubation of N2a/tau441 with forskolin, a
      specific activator of cAMP-dependent protein kinase (PKA), induced an increased
      phosphorylation level of tau at both PKA and non-PKA sites in a dose- and time
      dependent manner, and the hyperphosphorylation of tau was positively correlated
      with the elevation of PKA activity. When the cells were transitorily incubated
      with forskolin, a temporary activation of PKA with a sustained and almost equally
      graded tau hyperphosphorylation at some non-PKA sites was observed. In either
      case, the activity of glycogen synthase kinase-3 (GSK-3) was not changed. It is
      suggested that only transitory activation of PKA in early stage of Alzheimer
      disease may result in a sustained tau hyperphosphorylation at multiple sites,
      implying a new mechanism to Alzheimer-like tau hyperphosphorylation.

PMID- 16465465
TI  - Family-based association studies of the TCP1 gene and schizophrenia in the
      Chinese Han population.
AB  - A previous case-control study by Yang et al. indicated that the TCP1 gene in 6q25
      was associated with schizophrenia in the Han population. To replicate this
      result, we selected eight SNPs (rs2273828, rs3818298, rs1547094, rs1547093,
      rs2295898, rs2295899, rs4832, rs15982) spanning the whole gene and performed a
      family-based study using 325 trios samples. Our transmission disequilibrium test
      showed neither allele nor haplotype association with schizophrenia, and suggests
      that the TCP1 locus is not associated with schizophrenia in the Chinese
      population. Since 6q25 has consistently been found to be a susceptible region for
      schizophrenia, we suggest that other genes within this region should be the focus
      of attention.

PMID- 16465466
TI  - 7-Nitroindazole potentiates the anticonvulsant action of some second-generation
      antiepileptic drugs in the mouse maximal electroshock-induced seizure model.
AB  - The effects of 7-nitroindazole (7NI, a preferential neuronal nitric oxide
      synthase inhibitor) on the anticonvulsant activity of four second-generation
      antiepileptic drugs (AEDs: felbamate [FBM], lamotrigine [LTG], oxcarbazepine
      [OXC] and topiramate [TPM]) were studied in the mouse maximal electroshock
      induced seizure (MES) model. Moreover, the influence of 7NI on the acute
      neurotoxic (adverse-effect) profiles of the studied AEDs, with regard to motor
      coordination, was determined in the chimney test in mice. Results indicate that
      7NI (50 mg/kg; i.p.) significantly potentiated the anticonvulsant activity of
      OXC, but not that of FBM, LTG and TPM against MES-induced seizures and,
      simultaneously, it enhanced the acute neurotoxic effects of TPM, but not those of
      FBM, LTG and OXC in the chimney test in mice. 7NI at the lower dose of 25 mg/kg
      had no effect on the antiseizure activity and acute neurotoxic profiles of all
      investigated AEDs. Pharmacokinetic evaluation of interactions between 7NI and
      LTG, OXC and TPM against MES-induced seizures revealed no significant changes in
      free (non-protein bound) plasma AED concentrations following 7NI administration.
      Moreover, none of the examined combinations of 7NI with AEDs from the MES test
      were associated with long-term memory impairment in mice subjected to the step
      through passive avoidance task. Based on our preclinical study, it can be
      concluded that only the combination of 7NI with OXC was beneficial, when
      considering its both anticonvulsant and acute neurotoxic effects. Moreover, the
      lack of impairment of long-term memory and no pharmacokinetic interactions in
      plasma of experimental animals make the combination of 7NI with OXC worthy of
      consideration for the treatment of patients with refractory epilepsy. The other
      combinations tested between 7NI and LTG, FBM and TPM were neutral, when
      considering their both anticonvulsant effects and acute neurotoxic profiles,
      therefore, no useful recommendation can be made for their clinical application.

PMID- 16465467
TI  - Development of a mouse model of ethanol addiction: naltrexone efficacy in
      reducing consumption but not craving.
AB  - The aim of the present study was validating pharmacologically a mouse model of
      alcohol addiction. Mice (n = 60) were offered ethanol (5% and 10%) and water in a
      free choice paradigm consisting of four phases: free choice (10 weeks),
      withdrawal (2 weeks), re-exposure (2 weeks) and quinine- adulteration (2 weeks).
      Control mice (n = 10) had access to water. They were housed individually with
      food ad libitum. The animals' behaviour was evaluated at the beginning of the
      treatment and during the withdrawal period. After the exposure to the model, mice
      received i.p. naltrexone (0.0; 0.125; 2.0 and 16.0 mg/kg) or saline. Mice were
      characterized as: addicted (n = 15, preference for ethanol without reducing
      intake when ethanol were adulterated with quinine); heavy drinker (n = 14,
      preference for ethanol but reduced intake when ethanol were adulterated); and
      light drinker (n = 16, no preference for ethanol). Naltrexone reduced ethanol
      intake in the heavy and light groups (p <or= 0.01 and p <03= 0.05, respectively,
      compared to saline-treated group) with no effect on water intake. It is discussed
      that naltrexone may be acting in the positive reinforcing properties of ethanol
      but does not seem to have anti-craving properties. It was concluded that the
      addicted mice had a compulsive behavior manifested by the continued ethanol
      intake even under aversive conditions and under naltrexone treatment suggesting
      that this model might be useful to study addiction.

PMID- 16465468
TI  - Theory of myelin coiling.
AB  - A new model is proposed to explain coiling of myelins composed of fluid bilayers.
      This model allows the constituent bilayer cylinders of a myelin to be non-coaxial
      and the bilayer lateral tension to vary from bilayer to bilayer. The calculations
      show that a myelin would bend or coil to lower its free energy when the bilayer
      lateral tension is sufficiently large. From a mechanical point of view, the
      proposed coiling mechanism is analogous to the classical Euler buckling of a thin
      elastic rod under axial compression. The analysis of a simple two-bilayer case
      suggests that a bilayer lateral tension of about 1 dyne/cm can easily induce
      coiling of myelins of typical lipid bilayers. This model signifies the importance
      of bilayer lateral tension in determining the morphology of myelinic structures.

PMID- 16465470
TI  - Muscle microanatomy and its changes during contraction: the legacy of William
      Bowman (1816-1892).
AB  - Striated muscle fine structure began to be really understood following a
      comprehensive survey of the matter carried out by William Bowman in the late
      1830s. The publications resulting from such a study, the first of which earned
      for the author a precocious election as Fellow of the Royal Society, are herewith
      examined in the context of contemporary views on the subject as well as of their
      subsequent repercussion and current knowledge today. It is shown that not only
      Bowman succeeded in establishing the true architecture of striated muscle fibres
      to the extent possible with the most advanced technology available in his day-
      explaining and eradicating alternative erroneous concepts in the process--but
      also in correctly describing the basic microstructural changes associated with
      contraction. In addition, although unrecognized by him or others at the time, his
      experiments with muscle provided direct evidence for the existence of a
      selectively permeable cell membrane--in the present meaning of the word--over
      half a century before its officially accepted discovery. Yet, in spite of these
      remarkable advances, Bowman arrived at the conclusion that the structure of
      striated muscle fibres is essentially irrelevant for the mechanism of
      contraction. Possible reasons behind Bowman's breakthrough accomplishments as a
      pioneer of modern muscle research, and his failure to understand their
      significance for muscle physiology, are discussed.

PMID- 16465469
TI  - Physiological consequences of thin filament cooperativity for vertebrate striated
      muscle contraction: a theoretical study.
AB  - Bindings of both myosin and Ca(2+) to the thin filament of vertebrate striated
      muscle are known to be strongly cooperative. Here the relation between these two
      sources of cooperativity and their consequences for physiological properties are
      assessed by comparing two models, with and without Monod-type myosin-binding
      cooperativity. In both models a thin filament regulatory unit (RU) is in either
      'off' or 'on' state, and the equilibrium between them (K (on)) is [Ca(2+)]
      dependent. The calculations predict the following: (1) In both models, myosin
      binding stabilizes the RU in the 'on' state, causing troponin to trap Ca(2+).
      This stabilization in turn increases the Ca(2+)-binding cooperativity, ensuring
      efficient regulation to occur in a narrow [Ca(2+)] range. (2) In the cooperative
      model, the RU is stabilized with a relatively low myosin affinity for actin (K
      approximately approximately 1), while the non-cooperative model requires a much
      higher affinity (K approximately approximately 10) to produce the same effect.
      (3) The cooperative model reproduces the known effects of [Ca(2+)] on the rate of
      force development and shortening velocity with a low K, but again the non
      cooperative model requires a higher value. (4) Because of the finite value of K
      (on), the thin filaments can never be fully activated by increasing [Ca(2+)],
      indicating that contracting muscles are under strong influence of thin-filament
      cooperativity even at saturating [Ca(2+)]. Interpretation of data on muscle
      mechanics without considering these cooperative effects could therefore lead to a
      substantial (10-fold) overestimate of cross-bridge binding properties.

PMID- 16465471
TI  - Plasticity of cardiac titin/connectin in heart development.
AB  - Many sarcomeric proteins in the myocardium alter their isoform pattern during
      perinatal development to adjust to the intensified pump function of the postnatal
      heart. These changes also involve the giant protein titin/connectin. Here we show
      by low-percentage polyacrylamide-gel electrophoresis that developmentally
      regulated switching of cardiac titin/connectin size occurs in the hearts of
      mouse, rat, pig, and chicken. Mammalian hearts express, well before birth, large
      foetal (approximately 3.7 MDa) N2BA-titin/connectin isoform but no N2B-isoform
      (3.0 MDa). During perinatal heart development the 3.7-MDa N2BA-isoform is
      replaced by a mix of smaller isoforms. At birth a plethora of intermediate-size
      N2BA-isoforms appears together with the N2B-isoform. In postnatal heart
      development the larger-size N2BA-isoforms disappear and smaller-size N2BA
      isoforms are upregulated, whereas the proportion of N2B-titin/connectin increases
      to species-specific adult levels. The time courses of isoform switching are
      faster in small than in large mammals. Titin/connectin isoform switching also
      takes place in developing chicken hearts, but the largest embryonic isoform found
      here was less than 3.4 MDa. At hatching, various smaller-size isoforms appeared
      and within a week the adult expression pattern was established representing a
      major 3.0-MDa isoform and a minor 3.15-MDa isoform. The ratio between the two
      adult isoforms differed between the left ventricle and the right atrium. The
      perinatal changes toward smaller cardiac titin/connectin isoforms in mammals and
      chicken greatly increase the myofibrillar passive tension of postnatal hearts.
      Plasticity of titin/connectin at approximately the time of birth thus affects
      myocardial mechanics but could also be an important factor in developmentally
      regulated assembly and signalling processes.

PMID- 16465472
TI  - Titin PEVK segment: charge-driven elasticity of the open and flexible
      polyampholyte.
AB  - The giant protein titin spans half of the sarcomere length and anchors the myosin
      thick filament to the Z-line of skeletal and cardiac muscles. The passive
      elasticity of muscle at a physiological range of stretch arises primarily from
      the extension of the PEVK segment, which is a polyampholyte with dense and
      alternating-charged clusters. Force spectroscopy studies of a 51 kDa fragment of
      the human fetal titin PEVK domain (TP1) revealed that when charge interactions
      were reduced by raising the ionic strength from 35 to 560 mM, its mean
      persistence length increased from 0.30 +/- 0.04 nm to 0.60 +/- 0.07 nm. In
      contrast, when the secondary structure of TP1 was altered drastically by the
      presence of 40 and 80% (v/v) of trifluoroethanol, its force-extension behavior
      showed no significant shift in the mean persistence length of approximately
      approximately 0.18 +/- 0.03 nm at the ionic strength of 15 mM. Additionally, the
      mean persistence length also increased from 0.29 to 0.41 nm with increasing
      calcium concentration from pCa 5-8 to pCa 3-4. We propose that PEVK is not a
      simple entropic spring as is commonly assumed, but a highly evolved, gel-like
      enthalpic spring with its elasticity dominated by the sequence-specific charge
      interactions. A single polyampholyte chain may be fine-tuned to generate a broad
      range of molecular elasticity by varying charge pairing schemes and chain
      configurations.

PMID- 16465473
TI  - Can the passive elasticity of muscle be explained directly from the mechanics of
      individual titin molecules?
AB  - Recent progress in understanding the role of titin/connectin in muscle elasticity
      has been heavily based on results from single molecule mechanical experiments.
      The shape of force-extension curves from such data is similar to curves from
      muscle fibres and it has been tempting to assume that muscle elasticity can be
      extrapolated directly from the single molecule data. In this paper we discuss
      some of the factors that act on titin in the sarcomere that are likely to
      preclude such a direct extrapolation.

PMID- 16465474
TI  - In indirect flight muscles Drosophila projectin has a short PEVK domain, and its
      NH2-terminus is embedded at the Z-band.
AB  - Insect indirect flight muscles (IFM) contain a third filament system made up of
      elastic connecting or C-filaments. The giant protein projectin is the main, if
      not the only, component of these structures. In this study we found that
      projectin is oriented within the IFM sarcomere with its NH2-terminus embedded in
      the Z-bands. We demonstrate that this protein has an elastic region that can be
      detected by the movement of specific epitopes following stretch. One possible
      elastic region is the PEVK-like domain located close to the NH2-terminus. The
      amino acid length of this region is short, and 52% of its residues are P, E, V or
      K. We propose a model in which projectin extends from the Z-band to the lateral
      borders of the A-band. The PEVK-like domain and a series of Ig domains spanning
      the intervening I-band may provide the elastic properties of projectin.

PMID- 16465475
TI  - Functional analysis of titin/connectin N2-B mutations found in cardiomyopathy.
AB  - Hypertrophic cardiomyopathy and dilated cardiomyopathy are two major clinical
      phenotypes of "idiopathic" cardiomyopathy. Recent molecular genetic analyses have
      now revealed that "idiopathic" cardiomyopathy is caused by mutations in genes for
      sarcomere components. We have recently reported several mutations in
      titin/connectin gene found in patients with hypertrophic cardiomyopathy or
      dilated cardiomyopathy. A hypertrophic cardiomyopathy-associated titin/connectin
      mutation (Arg740Leu) was found to increase the binding to actinin, while other
      dilated cardiomyopathy-associated titin/connectin mutations (Ala743Val and
      Val54Met) decreased the binding to actinin and Tcap/telethonin, respectively. We
      also reported several other mutations in the N2-B region of titin/connectin found
      in hypertrophic cardiomyopathy and dilated cardiomyopathy. Since the N2-B region
      expresses only in the heart, it was speculated that functional alterations due to
      the mutations cause cardiomyopathies. In this study, we investigated the
      functional changes caused by the N2-B region mutations by using yeast-two-hybrid
      assays. It was revealed that a hypertrophic cardiomyopathy-associated mutation
      (Ser3799Tyr) increased the binding to FHL2 protein, whereas a dilated
      cardiomyopathy-associated mutation (Gln4053ter) decreased the binding. In
      addition, another TTN mutation (Arg25618Gln) at the is2 region was found in
      familial DCM. Because FHL2 protein is known to tether metabolic enzymes to N2-B
      and is2 regions of titin/connectin, these observations suggest that altered
      recruitment of metabolic enzymes to the sarcomere may play a role in the
      pathogenesis of cardiomyopathies.

PMID- 16465478
TI  - Subcutaneous panniculitis-like T-cell lymphoma presenting with hemophagocytic
      lymphohistiocytosis and skin lesions with characteristic high-resolution
      ultrasonographic findings.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an unusual type of skin
      lymphoma, characterized by subcutaneous soft tissue infiltration with pleomorphic
      T-cells and benign macrophages that mimic panniculitis. Hemophagocytic
      lymphohistiocytosis is a rare but potentially fatal disorder which is thought to
      result from uncontrolled activation and proliferation of T-cells and excessive
      activation of macrophages. Hemophagocytic lymphohistiocytosis have been reported
      as the presenting feature in 37% of SPTCL patients. High-resolution
      ultrasonographic appearance of SPTCL with a characteristic finding has been
      described in only one patient. We report a 28-year-old woman with hemophagocytic
      lymphohistiocytosis presented with nonremitting fever, thrombocytopenia,
      hypofibrinogenemia, hyperferritinemia, increased serum levels of soluble
      interleukin (IL)-2 receptors and hemophagocytosis in bone marrow examination.
      Markedly elevated level of serum IL-18 was also demonstrated in our patient. The
      fever subsided and the ferritin level declined to normal after treatment with
      oral steroid and etoposide. No evidence of hemophagocytosis was revealed in a
      follow-up bone marrow examination. However, nonremitting high fever and
      panniculitis-like skin lesions over her back, arm, lower abdominal wall, and
      bilateral pretibial regions developed 1 month later. A high-resolution
      ultrasonography revealed thickening of the subcutaneous fat layer with
      homogeneous hyperechogenicity pattern and poor-defined margin over the skin
      lesions. An ultrasound-guided excision biopsy of the nodular lesion over left
      upper arm was performed and the histopathology showed neoplastic cells with
      hyperchromatic nucleoli, which extended from deep dermis to subcutaneous fat. The
      immunochemical stain showed a T-cell lineage of tumor cells. SPTCL was diagnosed
      and the skin lesions subsided gradually after treatment with anthracycline-based
      combination chemotherapy.

PMID- 16465479
TI  - Kikuchi-Fujimoto disease coexisted with Sjogren's syndrome.
AB  - Here we described a case of primary Sjogren's syndrome that coexisted with
      Kikuchi-Fujimoto disease.

PMID- 16465476
TI  - How to build a myofibril.
AB  - Building a myofibril from its component proteins requires the interactions of
      many different proteins in a process whose details are not understood. Several
      models have been proposed to provide a framework for understanding the increasing
      data on new myofibrillar proteins and their localizations during muscle
      development. In this article we discuss four current models that seek to explain
      how the assembly occurs in vertebrate cross-striated muscles. The models
      hypothesize: (a) stress fiber-like structures as templates for the assembly of
      myofibrils, (b) assembly in which the actin filaments and Z-bands form subunits
      independently from A-band subunits, with the two subsequently joined together to
      form a myofibril, (c) premyofibrils as precursors of myofibrils, or (d) assembly
      occurring without any intermediary structures. The premyofibril model, proposed
      by the authors, is discussed in more detail as it could explain
      myofibrillogenesis under a variety of different conditions: in ovo, in explants,
      and in tissue culture studies on cardiac and skeletal muscles.

PMID- 16465481
TI  - Maternal and genetic effects on anxiety-related behavior of C3H/HeN, DBA/2J and
      NMRI mice in a motility-box following blastocyst transfer.
AB  - Reciprocal embryo transfers were conducted to examine genetic and maternal
      effects on the behavior of inbred C3H/HeN and DBA/2J mice, and outbred NMRI mice
      using a motility-box. The behavioral variables measured were (i) horizontal
      locomotor activity assessed as the path and time spent during traveling; (ii)
      vertical activity assessed as the time spent with and numbers of
      rearings/leanings; (iii) and the time spent in the more anxiogenic central field.
      The transfer procedure per se resulted in a minor increase in vertical activity
      of inbred C3H/HeN mice, but had no effect in inbred DBA/2J mice. In contrast,
      outbred NMRI mice displayed a lower central field activity following embryo
      transfer indicating a higher anxiety level. Moreover, genetic differences between
      the mouse strains studied remained stable following embryo transfer for locomotor
      and vertical activity, but not central field activity depending on the recipient
      mother strain. Maternal effects were found for (i) vertical activity in the two
      inbred mouse strains, (ii) all behavioral variables studied in outbred NMRI mice,
      and (iii) an interaction with gender for the time spent in the anxiogenic central
      field. An additional fostering procedure revealed that the vertical activity of
      NMRI mice was modified towards the behavior of the recipient C3H/HeN strain by
      uterine factors, whereas the postnatal maternal effect of C3H/HeN mothers was the
      opposite. In summary, the effects of the embryo transfer procedure per se,
      stability of genetic characteristics following embryo transfer and maternal
      effects were related to the mouse strains used as donators and recipients, and
      the behavioral variables studied.

PMID- 16465480
TI  - Genetic and environmental contributions to common psychopathologies of childhood
      and adolescence: a study of twins and their siblings.
AB  - We report findings based on analyses of self-reports of six common adolescent
      psychopathologies (attention deficit/hyperactivity disorder, ADHD; conduct
      disorder, CD; oppositional defiant disorder, ODD; generalized anxiety disorder,
      GAD; separation anxiety disorder, SAD; and major depressive disorder, MDD) in a
      sample of 1,162 male and female adolescent (12-19 years) twin pairs and 426
      siblings. Prevalence statistics for past year and lifetime reports confirm
      differences between genders for CD, GAD, SAD, and MDD, and a lack of differences
      between twins and their non-twin siblings. Biometrical modeling was conducted to
      ascertain the relative influences of genes, and shared and non-shared
      environments contributing to these disorders. A more robust estimate of these
      parameters was obtained by including non-twin siblings. Age-specific thresholds
      were integrated into the analyses to appropriately model the developmental
      patterns of behavior. We found evidence for both genetic and non-shared
      environmental influences for all disorders. Shared environmental influences also
      seem to be important for MDD and lifetime GAD.

PMID- 16465482
TI  - The effects of changes in extracellular calcium concentrations on the electrical
      properties of command neurons after acquisition of a defensive conditioned reflex
      in snails.
AB  - Studies of the electrical characteristics of the command neurons of a defensive
      reflex showed that the membrane potential showed no significant changes in
      response to changes in the calcium concentration in the perfusing solution in
      either intact or trained snails. Increases in the calcium ion concentration in
      intact snails were accompanied by increases in the threshold potential, from 14
      +/- 0.7 mV at 2.5 mM Ca2+ to 21.8 +/- 0.9 mV at 20 mM Ca2+. The threshold
      potential in trained snails decreased in response to both increases and decreases
      in calcium concentrations, from 16.8 +/- 0.6 mV (physiological saline containing
      10 mM Ca2+) to 13.3 +/- 0.6 mV at 20 mM Ca2+ and 11.8 +/- 0.8 mV at 2.5 mM Ca2+.
      The critical depolarization level changed correspondingly: in intact snails, this
      decreased with increases in calcium concentration, while in trained snails it
      increased in response to both increases and decreases in the calcium
      concentration.

PMID- 16465483
TI  - Characteristics of neuron activity in the honey bee (Apis mellifera L.) in
      conditions of kynurenine deficiency.
AB  - Neuron activity was studied electrophysiologically in the antennal lobes,
      mushroom bodies, and cervical connective during ontogenesis (days 1, 3, 7, and
      25) in snow(laranija) mutant bees, which suffer kynurenine deficiency, and in
      wild-type bees. Neuron activity recorded from the cervical connective was found
      to show the greatest dependence on kynurenine content. Mutation in the structural
      gene for tryptophan oxygenase, the first and key enzyme in the kynurenine pathway
      for tryptophan metabolism (KPTM) and which leads to kynurenine deficiency,
      decreased the frequency of neuron spike activity recorded from the cervical
      connective. This would appear to be associated with a possible deficiency of
      glutamic acid; it was independent of the deficiency of kynurenic acid and
      kynurenine, a point subject to further studies. Clear manifestation of the effect
      of the mutation requires the presence of two mutant alleles in the bee genome
      (homozygosity). The effect of the mutation, to inhibit neuron activity in the
      cerebral ganglion, corresponds to the effect seen previously at the behavioral
      level. Less clear effects were obtained from recordings of neuron activity from
      the antennal lobes and mushroom bodies. This may be associated with the
      complexity of the spectrum of biochemical lesions in different parts of the brain
      resulting from the mutation.

PMID- 16465484
TI  - Linkage of neuron spike activity in the right and left amygdala in food
      motivation and emotional tension.
AB  - Cross-correlation histograms were plotted to study the linkage of spike activity
      in simultaneously recorded neurons in the central nucleus of the right and left
      amygdala in rabbits in calm waking, after 24 hours of food deprivation, in
      satiation, and in emotional tension (on presentation of dogs). Histograms showed
      peaks displaced from zero in 50-67% of cases. In hunger, many cases (52%) showed
      pairs in which the first neuron to discharge was in the left amygdala, this being
      followed by a neuron in the right amygdala (peaks from 10-50 and 130-150 msec).
      Firing in the opposite order was seen more rarely (36%). On presentation of dogs,
      there was an increase in the number of cases showing a common input to neurons,
      along with an increase in the leading role of neurons in the right amygdala
      (57%), due to increases in inhibitory influences from this area on cells in the
      left amygdala. The interaction of amygdalar neurons in these states was in most
      cases at frequencies in the delta range (74%), mainly at 2-4 Hz.

PMID- 16465485
TI  - Spontaneous activity and rhythm assimilation reactions in baby rabbit hippocampal
      neurons during learning: age-related characteristics.
AB  - The neural mechanisms of the age-related characteristics of memory formation were
      studied in experiments based on a model providing an analog of a conditioned
      reflex to time: trace assimilation of the rhythm with which neurons in
      hippocampal field CA1 were stimulated, in rabbits aged 1-4 weeks and 5-6 months.
      Stages of changes in neuron spike activity characteristic for developing animals
      were described. In animals studied one week after birth, there was a predominance
      of silent cells and cells with low spontaneous activity. At 2-3 weeks of life,
      the level of spontaneous neuron activity increased, reaching adult levels by 25
      30 days. The dynamics of the ontogenetic development of learning ability showed a
      number of stages: from virtually complete inability to form and assimilate traces
      of the rhythm (at age 6-7 days) to the stage of good formation and rapid
      forgetting (8-14 days), and, finally, the development of complete memory (25-30
      days). The synchronous development of plastic rearrangements and the level of
      spontaneous neuron activity provided evidence of the direct involvement of the
      mechanisms underlying the formation of spontaneous spike activity in the
      organization of neural processes supporting adaptive reactions in the developing
      animal.

PMID- 16465486
TI  - Computation of color and brightness differences by rabbit visual cortex neurons.
AB  - Extracellular recording of the activity of 54 neurons in the rabbit visual cortex
      in responses to substitutions of eight colored and eight monochromatic stimuli in
      pairs was studied. Stimuli were uniform flashes of light displayed on an SVGA
      monitor and illuminated the whole retina. The responses of phasic neurons showed
      an initial discharge (50-90 msec from the moment of the change in stimulus),
      associated with the brightness or color difference between the stimuli. These
      "discrimination discharges" were used to construct an 8 x 8 matrix for each
      neuron, showing the mean number of spikes per sec in responses to changes in
      different pairs of stimuli. Processing of the matrix by factor analysis
      identified the major factors determining the axes of the sensory space. A
      brightness space with only two dimensions, with darkness and brightness
      orthogonal axes, was seen for 30% of neurons. A four-dimensional color space was
      seen in 22% of neurons, with two color and two achromatic axes. The sensory space
      of these neurons was similar to the spaces obtained by analyzing the early
      components of visual evoked potentials in rabbits induced by changes in color
      stimuli and behavioral operant responses in conditioned reflex color
      differentiation. The fundamental coincidence of the sensory spaces obtained by
      different methods identifies the general nature of the principle of vector coding
      and the existence of special neuronal mechanisms for detection of color and
      brightness differences in the visual field.

PMID- 16465487
TI  - Glutamate release in the nucleus accumbens during competitive presentation of
      aversive and appetitive stimuli.
AB  - In vivo intracerebral microdialysis/HPLC studies on Sprague-Dawley rats showed
      that simultaneous presentation of food and a tone previously combined with a pain
      stimulus was accompanied by transient elevation of the glutamate level in the
      extracellular space of the nucleus accumbens, the extent of this increase being
      proportional to the latent period of initiation of the act of eating. Conversely,
      sequential presentation of the conditioned aversive signal followed by food and
      isolated presentation of the conditioned aversive signal alone were not
      accompanied by changes in the level of extracellular glutamate. It is suggested
      that glutamate release in the nucleus accumbens in conditions of competition
      between presentation of food and a tone previously combined with pain stimulation
      is not related to the process of selecting between the aversive and appetitive
      strategies of behavior, but may be associated with inhibition of preparation to
      perform or performance of the food-related behavior.

PMID- 16465488
TI  - Functions of peptide CNP4, encoded by the HCS2 gene, in the nervous system of
      Helix lucorum.
AB  - The aims of the present work were to study the role of neuropeptide CNP4, encoded
      by the HCS2 gene (which is expressed mainly in parietal command interneurons), in
      controlling the activity of the respiratory system, and also to study the effects
      of this neuropeptide on isolated defensive behavior neurons in prolonged culture.
      The influence of the command interneuron on the pneumostoma included a direct
      effect consisting of closure and a delayed effect consisting of intensification
      of respiratory movements. Application of neuropeptide CNP4 produced a pattern
      similar to the delayed effects seen on stimulation of the command interneuron,
      i.e., significant increases in the frequency and intensity of pneumostoma
      movements and strengthening of the rhythmic activity of the pneumostoma
      motoneuron. Studies of the effects of neuropeptide CNP4 on isolated neurons after
      prolonged culture showed that neuron process growth correlated with the presence
      of the neuropeptide in the medium. Identification of the location of the HCS2
      precursor protein and neuropeptide CNP4 in isolated command interneurons after
      prolonged culture showed that that only those parts of the cell showing active
      process growth were immunopositive. Thus, neuropeptide CNP4 appears to be a
      secreted neuropeptide controlling respiratory system activity, which may also be
      involved in rearrangements of the network controlling defensive behavior in Helix
      snails.

PMID- 16465489
TI  - Sexual dimorphism of neuroglial relationships in the frontal fields of the human
      brain.
AB  - Cytoglioarchitectonic and quantitative methods were used to study the
      characteristics of neuroglial relationships in fields in the frontal areas of the
      male and female brains. Series of frontal paraffin sections of thickness 20
      microm stained by the Nissl method were used to study fields 8, 12, 47, and 10.
      In layers III and V of the right and left hemispheres, the densities of pyramidal
      neurons (N), satellite gliocytes (SG), and N surrounded by SG (SN) per 0.001 mm3,
      and the SN/N ratio (%) were useful measures of the functional-metabolic activity
      of the brain. In women, SG, SN, and SN/N were higher in fields 12, 47, and 10
      than in men, but were lower in field 8. It is suggested that cortical N have
      greater metabolic activity in women in emotional-volitional and "intellectual"
      structures, while men have more N in the motor areas.

PMID- 16465490
TI  - Quantitative characteristics of the associative projections of field 4y to
      subfields of the sensorimotor and parietal cortex of the cat.
AB  - The Nauta-Gygax method was used to study the ipsilateral associative connections
      of motor cortex field 4y after local electrolytic lesioning of this zone. The
      relative quantitative distribution of associative fibers running from field 4y to
      somatosensory areas I and II, the motor cortex, and the parietal cortex was
      determined. The greatest projections of field 4y were found to be directed to
      field 2pri (the secondary somatosensory zone) and field 5ab. Occasional
      degenerative fibers passed to fields 1, 2, 3a, and 3b of the primary
      somatosensory zone of the cortex. Efferent fibers from field 4y were not directed
      to fields 4fu, 4sfu, 6aa, 6ab, or 6ifu. It is suggested that the morphological
      basis of motor reactions mediated by field 4y is not provided by the fundal (4fu,
      4sfu, 6ifu) or premotor (6aa, 6ab) fields but by field 2pri and 5ab, with which
      it has more extensive connections.

PMID- 16465491
TI  - Cellular composition of the piriform cortex of the rat brain in experimental
      epilepsy.
AB  - The cellular composition of all layers of the anterior, central, and posterior
      parts of the piriform cortex of the rat brain was studied two weeks and one month
      after specific electrical stimulation (kindling) of the ventral hippocampus.
      Stereomicroscopic analysis at both two weeks and one month after kindling showed
      significant decreases in the numbers of pyramidal cells and interneurons in all
      layers of all parts of the piriform cortex. At two weeks, the numbers of
      pyramidal cells and interneurons in the central part of the piriform cortex also
      decreased in rats in which electrodes were inserted into the ventral hippocampus
      but without stimulation. These results, along with published data, led to a
      series of suggestions regarding the involvement of the piriform cortex in
      epileptogenesis.

PMID- 16465492
TI  - Formation of the astroglia in the mouse neocortex after temporary prenatal
      blockade of serotonin synthesis.
AB  - The dynamics of the appearance of astrocytes in the mouse neocortex after
      prenatal blockade of serotonin synthesis was studied. Experiments were performed
      on F1(CBA/C57Bl) hybrid mice. Serotonin release was suppressed with
      parachlorophenylalanine, given as single doses to mothers during the early
      postimplantation stage of pregnancy. Astrocytes differentiating in the brain were
      visualized by an immunohistochemical method for detecting astrocyte intermediate
      filament protein, this being a specific glial fibrillary acidic protein (GFAP)
      allowing not only marking of cells, but also assessment of the presence, extent,
      and rate of cell differentiation. The results showed that in normal conditions,
      GFAP-positive cells appeared in layer I of all neocortical areas during the first
      week after birth, i.e., the area cingularis, the area occipitalis, the area
      parietalis, the area insularis, the area praepiriformis, the area piriformis, the
      area entorhinalis, and the area subiculum. The process of astrocyte
      differentiation intensified with development. Barrier structures also formed.
      During the first days of postnatal development, astrocytes and their processes
      appeared around vessels and the walls of the lateral ventricles. The neocortex of
      rats developing in conditions of blockade of serotonin synthesis showed smaller
      numbers of GFAP-positive cells, particularly in the white matter, at all stages
      of postnatal development studied.

PMID- 16465493
TI  - Structural changes in the nucleus ambiguus of the medulla oblongata and
      intracardiac ganglia in growing rats in immobilization stress.
AB  - The aim of the present work was to study qualitative and quantitative measures of
      histological changes in the nucleus ambiguus (NA) of the medulla oblongata and
      the cardiac autonomic ganglia (CAG) in growing animals in conditions of
      immobilization stress of different durations. Experiments were performed on 56
      mongrel white rats aged 30 days. Immobilization stress was produced by placing
      rats in a special apparatus with a controllable internal volume for 3, 7, 15, and
      30 days. The NA and CAG were studied on paraffin sections using neurohistological
      methods and quantitative analysis. Morphological and morphometric changes,
      consisting of a delay in the growth of neurocyte cell and nucleus volumes, as
      compared with controls, were seen both in the NA of the medulla oblongata and the
      CAG and were evaluated as impairments in the histogenesis of nerve tissue during
      postnatal ontogenesis. The extent of structural changes in these components of
      the autonomous nervous system was directly dependent on the duration of the
      experimental treatment.

PMID- 16465494
TI  - Characteristics of small neurons of the reticular thalamic nucleus in WAG/Rij
      rats.
AB  - The aim of the present work was to study the ultrastructure of small neurons in
      the reticular thalamic nucleus (RTN) in WAG/Rij rats, which are used as a model
      of absence epilepsy. A total of 24 rats were studied. The brains of 10 rats were
      used for studies of the cytoarchitectonics and cytological characteristics of
      neurons, for which paraffin sections were stained with cresyl violet by the Nissl
      method. Electron microscopic studies were performed by microscope-controlled
      harvesting of the RTN with fixation in 2.5% glutaraldehyde in phosphate buffer pH
      7.4. Small neurons were found to account for 5-8% of all neurons in the RTN.
      These had oval bodies, sparse and pale-staining cytoplasm, and were frequently
      located in pairs. The ultrastructure of these neurons was characterized by poor
      development of cell membranes, branching of the axon close to the cell body, and
      multiple axon contacts with the body and dendrites. It is suggested that these
      neurons are short-axon neurons.

PMID- 16465495
TI  - Suppression of glial fibrillary acidic protein expression in astrocytes of the
      superficial glial delimiting membrane in traumatic subarachnoid hemorrhage.
AB  - Astrocyte reactions to brain damage are usually accompanied by increases in glial
      fibrillary acidic protein (GFAP) expression, though it remains unclear whether
      this reaction is universal. The aim of the present work was to study the
      reactions of astrocytes in the superficial glial delimiting membrane of the human
      brain to traumatic subarachnoid hemorrhage. Light microscopy and
      immunocytochemical studies showed that GFAP expression is suppressed in
      astrocytes in the superficial glial delimiting membrane for periods of up to
      three days from the moment of craniocerebral trauma accompanied by subarachnoid
      hemorrhage. These data provide evidence for the existence of regional
      characteristics in the reactions of astrocytes.

PMID- 16465496
TI  - The role of the parafascicular complex (CM-Pf) of the human thalamus in the
      neuronal mechanisms of selective attention.
AB  - The reactions of 93 neurons in the parafascicular complex (CM-Pf) of the human
      thalamus were studied by microelectrode recording during stereotaxic
      neurosurgical operations in patients with spastic torticollis. High reactivity
      was demonstrated for two previously classified types of neurons with identical
      irregular (type A) and bursting Ca2+ -dependent (type B) activities in response
      to presentation of relevant verbal stimuli evoking selective attention in humans.
      Concordant changes in the network activity of A and B neurons were observed, in
      the form of linked activatory-inhibitory patterns of responses and the
      appearance, at the moment of presentation of an imperative morpheme of the
      command stimulus, of rapidly occurring intercellular interactions consisting of
      local synchronization with simultaneously developing rhythmic oscillatory (3-4
      Hz) activity. Data are presented on the existence of a direct connection between
      these neuronal rearrangements and activation of selective attention, providing
      evidence for the involvement of the thalamic parafascicular complex (CM-Pf) in
      the mechanisms of selective attention and processing of relevant verbal
      information during the preparative period of voluntary actions.

PMID- 16465498
TI  - The presynaptic effects of arachidonic acid and prostaglandin E2 at the frog
      neuromuscular junction.
AB  - Arachidonic acid and prostaglandin E2 decreased the frequency of miniature
      endplate potentials with producing any changes in the their amplitude-time
      parameters. Arachidonic acid and prostaglandin E2 decreased the quantum
      composition of endplate currents and the amplitude of the third phase of the
      nerve ending response, which reflects currents though potential-dependent K+
      channels. A perineural method was used to demonstrate that arachidonic acid and
      prostaglandin E2 suppressed the nerve ending Ca2+ current. The cyclooxygenase
      blocker indomethacin increased neurotransmitter secretion and decreased the third
      phase of the nerve ending response. The effects of arachidonic acid and
      prostaglandin E2 on evoked neurotransmitter release were not seen in the presence
      of indomethacin, while the third phase of the response continued to show a
      reduction. It is suggested that prostaglandin E2 mediates the effects of
      arachidonic acid on spontaneous and evoked neurotransmitter secretion, Ca2+
      currents, and Ca2+ -dependent K+ currents. In addition, arachidonic acid and
      prostaglandin E2 had their own effects on potential-dependent K+ currents in
      nerve endings.

PMID- 16465497
TI  - Vestibular influences on postural instability induced by movements of the visual
      environment and support.
AB  - Subjects were maintained in a vertical posture standing on a hard support with a
      limited degree of freedom in the frontal plane. The stability of the vertical
      posture was assessed on the basis of the standard deviations (sigma) from the
      mean amplitude of head oscillations (in the frontal and sagittal planes) relative
      to the origin of the coordinate system. Sinusoidal rotations of the optokinetic
      cylinder in which subjects stood, sinusoidal rotations of the support, and
      combination of these rotations, with phase discordance between movements of the
      cylinder and the support, led to increases in sigma in all subjects. Feedback via
      the vestibular input was created using transmastoid galvanic vestibular
      stimulation. Changes in the feedback current showed a linear function relating to
      the amplitude and speed of head movement. Introduction of variations in the
      feedback function could be used to decrease sigma for lateral oscillations;
      increases (compared with values on calm standing in the dark) resulted from the
      use of any of the destabilizing treatments. Changes in sigma for oscillations in
      the sagittal plane were not systematic.

PMID- 16465499
TI  - The role of defensin NP-1 in restoring the functions of an injured nerve trunk.
AB  - This report presents results from studies on the actions of neutrophil defensin
      NP-1 on the initial stage of regeneration of the lesioned sciatic nerve in rats.
      The effects of defensin on the growth rate and functional characteristics of
      regenerating nerve fibers were assessed by recording total action potentials 21
      days after transection and microsurgical suturing of the nerve. These experiments
      showed that defensin increased the rate of growth of regenerating nerve fibers by
      30%: the distance over which nerve spike conductivity was restored in the
      lesioned nerve increased from 7.2 +/- 1.2 (control) to 10.5 +/- 0.8 mm
      (experiment) from the suturing site (p < 0.05). In addition, an increase in the
      excitation conduction rate along the regenerating nerve fibers by 20% compared
      with control was observed. Overall, the results provide evidence for the positive
      effects of defensin on restoration of the functions of the lesioned nerve trunk.

PMID- 16465500
TI  - The three-dimensional electrical field around the body of the african snail
      Achatina fulica on activation of the giant neurons.

PMID- 16465501
TI  - Genitalic autogrooming: a self-filling trash collection system in crickets.
AB  - Insects groom almost all parts of the body surface with their legs and mouth
      parts. However, some body regions are difficult to reach and keep clean. One is
      the genital chamber located in the last abdominal segment in males which houses
      the phallic complex for copulation and production of the spermatophore. In the
      male cricket, foreign substances can enter the genital chamber when it is opened
      during copulation and spermatophore formation. Moreover, the dorsal pouch and
      ventral lobes of the phallic complex, which mould the attachment plate, tube, and
      ampulla of the spermatophore, are inevitably soiled as a result of spermatophore
      production. We found a unique cleaning system in which foreign substances
      accumulated during copulation and spermatophore debris left in the dorsal pouch
      after copulation are quickly removed and collected in special pockets in the
      genital chamber. This trash is collected by undulation of the genital chamber's
      membranous floor which is entirely covered by small scales ( approximately 10
      microm) similar to those in the ovipositor of female crickets. This self-filling
      trash collecting system may be used in some other insects which produce the
      spermatophore in a similar manner to that of crickets.

PMID- 16465502
TI  - Determination of fumonisins B1 and B2 in Portuguese maize and maize-based samples
      by HPLC with fluorescence detection.
AB  - Fumonisins B(1) (FB1) and fumonisin B2 (FB2) are the main members of a family of
      mycotoxins produced by Fusarium verticillioides, Fusarium proliferatum, and other
      fungi species of the section Liseola. The present work shows the results of
      comparative studies using two different procedures for the analysis of fumonisins
      in maize and maize-based samples. The studied analytical methods involve
      extraction with methanol/water, dilution with PBS, and clean-up through
      immunoaffinity columns. Two reagents (o-phthaldialdehyde and naphthalene-2,3
      dicarboxaldehyde) were studied for formation of fluorescent derivatives. The
      separation and identification were carried out by high-performance liquid
      chromatography with fluorescence detection. The optimized method for analysis of
      fumonisins in maize involved extraction with methanol/water (80:20), clean-up
      with an immunoaffinity column, and derivatization with naphthalene-2,3
      dicarboxaldehyde (NDA). The limit of detection was 20 microg kg(-1) for FB1 and
      15 microg kg(-1) for FB2. Recoveries of FB1 and FB2 ranged from 79% to 99.6% for
      maize fortified at 150 microg kg(-1) and 200 microg kg(-1), respectively, with
      within-day RSDs of 3.0 and 2.7%. The proposed method was applied to 31 samples,
      and the presence of fumonisins was found in 14 samples at concentrations ranging
      from 113 to 2,026 microg kg(-1). The estimated daily intake of fumonisins was
      0.14 microg kg(-1) body weight per day.

PMID- 16465504
TI  - Quality assurance challenge 3.

PMID- 16465503
TI  - Biomolecular interaction analysis under electrophoretic flow conditions.
AB  - Combining the advantages of electrophoresis with the advantages of biomolecular
      interaction analysis (BIA) enables the biospecific detection of separated
      molecules; for example it permits differentiation between a complementary single
      stranded DNA and a single nucleotide polymorphism. In order to integrate these
      two techniques, it is necessary to investigate whether it is possible to detect a
      biomolecular interaction under electrophoretic flow conditions. To this end a
      novel detection system was developed for electrophoresis that utilizes a label
      free and time-resolved detection technique: reflectometric interference
      spectroscopy (RIfS). The biological functions of important analytes were
      investigated using this system. Although RIfS can be used as a postcolumn
      detector, it is also possible to use it to detect relevant substances under
      electrophoretic flow conditions. DNA-LNA, biotin-streptavidin and protein-protein
      interactions were detected using this coupled electrophoresis-RIfS set-up.

PMID- 16465505
TI  - Element fingerprinting of marine organisms by dynamic reaction cell inductively
      coupled plasma mass spectrometry.
AB  - A method for the determination of sixteen elements (Al, As, Cd, Co, Cr, Cu, Fe,
      Hg, Mn, Mo, Ni, Pb, Se, Sn, V, Zn) in seafood by dynamic reaction cell
      inductively coupled plasma mass spectrometry (ICP-DRC-MS) is presented. A
      preliminary study of polyatomic interferences was carried out in relation to the
      chemical composition of marine organisms belonging to different taxa. Acid
      effects and other matrix effects in marine organisms submitted to closed-vessel
      microwave digestion were investigated as well. Ammonia was the reactive gas used
      in the DRC to remove polyatomic ions interfering with 27Al, 52Cr, 56Fe and 51V.
      Optimal conditions for the simultaneous determination of analytes were identified
      in order to develop a fast multielement method. A suite of real samples (mussels
      and various fish species) were used during method development along with three
      certified reference materials: BCR CRM 278R (mussel tissue), BCR CRM 422 (cod
      muscle) and DORM-2 (dogfish muscle). The proposed analytical approach can be used
      in conjunction with suitable chemometric procedures to address quality and safety
      issues in aquaculture and fisheries. As an example, a case study is described in
      which mussels from three farming sites in the Venice Lagoon were distinguished by
      multivariate analysis of element fingerprints.

PMID- 16465506
TI  - Simultaneous determination of MHD and DMD in dog plasma by high-performance
      liquid chromatography with fluorescence detection and its application to
      pharmacokinetic studies.
AB  - A rapid, reproducible high-performance liquid chromatographic (HPLC) method with
      fluorescence detection for the simultaneous determination of 3(or 8)-(1
      methoxyethyl)-8(or 3)-(1-hydroxyethyl)-deuteroporphyrin IX (MHD) and 3,8-di-(1
      methoxyethyl)-deuteroporphyrin IX (DMD) in dog plasma was described. Fluorescein
      was used as an internal standard. A simple extraction step with ethyl acetate was
      performed before chromatography on a Diamonsil C18 column (5 microm, 4.6 mm x 150
      mm). The chromatography used 0.02 mol L(-1) sodium acetate/tetrahydrofuran (66:34
      v/v). The analytical curve was linear over the concentration range 0.025-2.5
      microg mL(-1). For a 100 microL dog plasma sample, the limit of determination for
      both MHD and DMD was 0.025 microg mL(-1). The recoveries of MHD and DMD were more
      than 76% and 89%, respectively. The intra-assay (within-run) and interassay
      (between-run) coefficients of variation (precisions) for MHD and DMD were less
      than 15%. This method was found to be suitable for the analysis of biosamples and
      was successfully applied to pharmacokinetic studies of Deuxemether in dogs.

PMID- 16465508
TI  - Lanthanide complex coordination polyhedron geometry prediction accuracies of ab
      initio effective core potential calculations.
AB  - lanthanide coordination compounds efficiently and accurately is central for the
      design of new ligands capable of forming stable and highly luminescent complexes.
      Accordingly, we present in this paper a report on the capability of various ab
      initio effective core potential calculations in reproducing the coordination
      polyhedron geometries of lanthanide complexes. Starting with all combinations of
      HF, B3LYP and MP2(Full) with STO-3G, 3-21G, 6-31G, 6-31G* and 6-31+G basis sets
      for [Eu(H2O)9]3+ and closing with more manageable calculations for the larger
      complexes, we computed the fully predicted ab initio geometries for a total of 80
      calculations on 52 complexes of Sm(III), Eu(III), Gd(III), Tb(III), Dy(III),
      Ho(III), Er(III) and Tm(III), the largest containing 164 atoms. Our results
      indicate that RHF/STO-3G/ECP appears to be the most efficient model chemistry in
      terms of coordination polyhedron crystallographic geometry predictions from
      isolated lanthanide complex ion calculations. Moreover, both augmenting the basis
      set and/or including electron correlation generally enlarged the deviations and
      aggravated the quality of the predicted coordination polyhedron crystallographic
      geometry. Our results further indicate that Cosentino et al.'s suggestion of
      using RHF/3-21G/ECP geometries appears to be indeed a more robust, but not
      necessarily, more accurate recommendation to be adopted for the general
      lanthanide complex case. [Figure: see text].

PMID- 16465507
TI  - [Complications of refractive excimer laser surgery].
AB  - In surface ablation, haze is the most frequent complication. After LASIK,
      microkeratome-related complications are rare today and usually resolve without
      sequelae, provided no ablation was done. Postoperative flap complications such as
      flap slippage usually occur during the first few days after surgery and should be
      treated as early whenever present. Interface complications are a new diagnostic
      entity as the interface between flap and stroma presents a space where fluid or
      cells can accumulate. Diffuse lamellar keratitis usually occurs within the first
      few postoperative days and should be treated aggressively to avoid scarring.
      Epithelial ingrowth is another rare complication usually requiring treatment.
      Corneal hydrops with fluid accumulation in the interface is a very rare but
      important phenomenon related to steroid-induced glaucoma but presenting with
      false low tonometry readings. Corneal ectasia is extremely rare and in most cases
      related to thin stromal beds. However, its pathogenesis is not yet completely
      understood, and it may occur in "normal" eyes, too. Dry eye syndrome is the most
      frequent complication after LASIK. It is usually benign but may cause significant
      visual impairment in rare cases.

PMID- 16465509
TI  - Chromosomal mapping of host resistance loci to Trichinella spiralis nematode
      infection in rats.
AB  - The differences in host response among strains of rats to intestinal nematode
      parasite Trichinella spiralis infection could provide a powerful benefit for
      further elucidation of molecular interactions between the host and the parasite.
      Using several strains of rats, we previously observed that DA strain is a strong
      responder and F344 strain is a weak responder with respect to expulsion of the
      adult worm. To identify the host resistance loci, quantitative trait loci (QTLs)
      analysis in F2 population from crosses between DA and F344 strains was performed.
      One significant QTL (designated as Tspe) was mapped to the middle region of
      chromosome 9. In addition, the effect of DA allele at Tspe locus could act
      recessively and lead to the rejection of more adult worms from the gut. The
      results from the present study provide more insights on host-parasite
      interactions, which may be useful in facilitating the development of novel
      approaches for treatment and control of intestinal parasites in human and
      domestic livestock.

PMID- 16465510
TI  - The pattern of clinical breast cancer metastasis correlates with a single
      nucleotide polymorphism in the C1qA component of complement.
AB  - Complement is one of primary defense mechanisms against intravascular
      microorganisms and could play a role in the immune response to malignancy and
      hence its clinical behavior. We evaluated if the sole coding polymorphism of C1qA
      associates with outcome in patients with breast carcinoma. Genotyping for
      C1qA[276A/G] was performed in 63 breast cancer subjects with localized tumor and
      compared with that in 38 breast cancer subjects with metastasis. Established risk
      factors for clinical outcome were considered and evaluated in multivariable
      analysis. Breast cancer subjects with heterozygous or homozygous C1qA[276G]
      genotype had a higher rate of metastasis than subjects with the homozygous
      C1qA[276A] genotype [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1
      4.1]. This association was stronger when only metastatic sites associated with
      hematogenous spread, i.e., to the bone, liver, and brain, were considered (HR
      3.5, 95% CI 1.4-5.6) and remained statistically significant after adjustment for
      the number of positive lymph nodes, estrogen receptor status, and progesterone
      receptor status. There was no statistical difference in the C1qA[276A/G] allelic
      distribution between all subjects with breast cancer and controls. These results
      suggest there could be an association of a single nucleotide polymorphism at
      position 276 of the C1qA component of complement with breast cancer metastasis to
      sites linked to hematogenous spread of disease. The C1qA polymorphism associated
      with decreased distant metastasis has also been correlated with an increased
      incidence of subcutaneous systemic lupus and C1q deficiencies, suggesting that an
      altered immune response may play a role in the observed association.

PMID- 16465511
TI  - Heritability of fasting glucose levels in a young genetically isolated
      population.
AB  - AIMS/HYPOTHESIS: The heritability of fasting glucose levels in Northern European
      populations has been examined previously in twins and samples of small pedigrees.
      In this study the heritability of fasting plasma glucose (FPG) was estimated in
      participants in the Erasmus Rucphen Family study, who were members of a single
      pedigree from a young genetic isolate. We also studied the relationship between
      FPG and components of the metabolic syndrome. METHODS: FPG, lipid, blood pressure
      and body composition measurements were completed for 852 participants without
      diabetic medication. The most significant predictors of FPG were used as
      covariates in heritability estimation. The sibship effect, which is a composite
      of genetic dominance and shared early-life environmental effects, was included as
      a random effect. RESULTS: The age- and sex-adjusted heritability of log normal
      transformed FPG was 36.6%. When further adjusted for metabolic risk factors,
      namely body composition parameters, systolic blood pressure, triglycerides and
      cholesterol: HDL ratio, the heritability estimate rose to 42.8%. After adjustment
      for the sibship effect, the additive component of heritability was estimated to
      be 28.3% (age- and sex-adjusted) and 24.9% (full model).
      CONCLUSIONS/INTERPRETATION: Genes control a significant proportion of the
      variance in FPG levels. Adjustment for other metabolic risk factors did not
      substantially change the heritability estimate, which suggests that a large part
      of the variance in FPG levels is due to genes that act through pathways that are
      independent of those controlling body composition, blood pressure and lipid
      levels.

PMID- 16465512
TI  - Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the
      in vitro formation of model foam cells from glycolaldehyde-modified low-density
      lipoproteins.
AB  - AIMS/HYPOTHESIS: Previous studies have shown that glycation of LDL by
      methylglyoxal and glycolaldehyde, in the absence of significant oxidation,
      results in lipid accumulation in macrophage cells. Such 'foam cells' are a
      hallmark of atherosclerosis. In this study we examined whether LDL glycation by
      methylglyoxal or glycolaldehyde, and subsequent lipid loading of cells, can be
      inhibited by agents that scavenge reactive carbonyls. Such compounds may have
      therapeutic potential in diabetes-associated atherosclerosis. MATERIALS AND
      METHODS: LDL was glycated with methylglyoxal or glycolaldehyde in the absence or
      presence of metformin, aminoguanidine, Girard's reagents P and T, or hydralazine.
      LDL modification was characterised by changes in mobility (agarose gel
      electrophoresis), cross-linking (SDS-PAGE) and loss of amino acid residues
      (HPLC). Accumulation of cholesterol and cholesteryl esters in murine macrophages
      was assessed by HPLC. RESULTS: Inhibition of LDL glycation was detected with
      equimolar or greater concentrations of the scavengers over the reactive carbonyl.
      This inhibition was structure-dependent and accompanied by a modulation of
      cholesterol and cholesteryl ester accumulation. With aminoguanidine, Girard's
      reagent P and hydralazine, cellular sterol levels returned to control levels
      despite incomplete inhibition of LDL modification. CONCLUSIONS/INTERPRETATION:
      Inhibition of LDL glycation by interception of the reactive aldehydes that induce
      LDL modification prevents lipid loading and model foam cell formation in murine
      macrophage cells. Carbonyl-scavenging reagents, such as hydrazines, may therefore
      help inhibit LDL glycation in vivo and prevent diabetes-induced atherosclerosis.

PMID- 16465513
TI  - To: Gerstein HC, Pogue J, Mann JFE, Lonn E, Dagenais GR, McQueen M, Yusuf S, for
      the HOPE investigators (2005) The relationship between dysglycaemia and
      cardiovascular and renal risk in diabetic and non-diabetic participants in the
      HOPE study: a prospective epidemiological analysis. Diabetologia 48:1749-1755.

PMID- 16465515
TI  - [Estimation of influenza vaccine effectiveness using routine surveillance data].
AB  - The continuous antigenic drift of influenza viruses requires annual adaptation of
      the vaccine. Protection depends largely on the match of the variants represented
      in the vaccine with the viruses actually known to be in circulation and may
      differ considerably from season to season. Therefore studies to assess the
      efficacy and effectiveness of the vaccine are conducted rather sporadically on an
      annual basis and it would be desirable to make use of routinely available data
      from surveillance programs. We compared two different approaches: (1) the
      "screening method" where cases are identified from laboratory data and controls
      are taken from data on vaccination rates and (2) a second method that uses the
      same cases, but controls were influenza-negative individuals with influenza-like
      illness (also identified from laboratory data). The sensitivity of the methods to
      confounders that were considered as relevant was tested with a simulation. Both
      methods were applied to the data of the German influenza surveillance data of the
      season 2004/2005. The estimated effectiveness over all age groups was rather low
      with both methods, but comparable with other estimations from the literature. We
      observed differences in certain age groups between the methods as well as large
      differences between particular age groups within one method. Possible
      explanations are random variations due to low numbers in age strata and other
      influences not yet considered. Therefore the estimations should be interpreted
      with care; however, relative comparisons among seasons may still be meaningful.

PMID- 16465516
TI  - [Health economics and HTA].
AB  - For a comprehensive health technology assessment (HTA), health economic studies
      are analysed as well as medical studies. Significance and effects of HTA are
      rather different in European countries. In Germany HTA is conducted by two
      official agencies: DIMDI and IQWiG. While DIMDI requires health economic
      assessments, IQWiG is prohibited from considering economic aspects by law (pure
      assessment of benefits). For the health economic assessment in HTA reports mainly
      secondary scientific evidence is exploited, i.e. primarily cost effectiveness and
      cost utility analyses. The study perspective, the study alternatives and the
      modelling methods are of great importance for the evaluation and have to be
      justified in depth. The cost effectiveness ratio and the budget impact are the
      most important results of the health economic assessment, which is the basis for
      the appraisal by the health care authorities. For this decision medical,
      utilitarian or other aspects like the avoidance of unwanted distribution effects
      are considered. On the other hand often only a few studies are available for the
      decision making when the appraisal has to be done. This problem might be less
      relevant in the near future as the number of HTAs and the number of health
      economic evaluations increases.

PMID- 16465514
TI  - Hypoxia-induced increase of endostatin in murine aorta and lung.
AB  - In the lung, hypoxia induces pulmonary hypertension caused by vasoconstriction
      and vascular remodeling. Additionally, hypoxia is an inducer of angiogenesis,
      which is assumed to counteract pulmonary hypertension. We asked whether the anti
      angiogenic factor endostatin--a cleavage product of collagen XVIII--participates
      in the vascular alterations induced by hypoxia. By employing Western blotting of
      tissue extracts of murine brain, liver and heart an endostatin fragment of 22 kDa
      was detectable, whereas in lung and aorta additional bands of 24 and 26 kDa were
      found. The amount of these larger fragments was increased in tissues obtained
      from mice housed for 4 days or 3 weeks at hypobaric hypoxia. By
      immunohistochemistry endostatin was detected in association with elastic fibers
      and in close neighborhood to smooth muscle cells of intrapulmonary vessels and
      the aorta. In the lung, the activity of matrix metalloproteinases (MMP) known to
      generate endostatin by cleavage of collagen XVIII was increased (MMP-2) and
      decreased (proMMP-9), respectively, by hypoxia. Elevated amounts of endostatin
      within the aortic wall of mice exposed to hypobaric hypoxia may stabilize the
      vascular wall by inhibition of microvascular sprouting. The surprising finding of
      increased endostatin in the lung presumably contributes to the development of
      pulmonary hypertension by reduction of angiogenesis.

PMID- 16465517
TI  - [The German Network for Evidence-based Medicine -- DNEbM].
AB  - The German Network for Evidence-based Medicine (DNEbM) was founded in October
      2000. A major impetus for the development of evidence-based medicine (EBM) in
      Germany came in the mid-1990s from the German Cochrane Initiative, which referred
      to the principles and activities of the international Cochrane Collaboration. The
      Network's primary mission is to establish a competence and reference centre for
      all aspects of evidence-based medicine. Central to this mission is to encourage
      projects that are concerned with scientific and methodological problems, aspects
      of professional development and the question of how to translate EBM into
      clinical practice. With currently more than 600 individual members the DNEbM is
      the most important society concerned with EBM in the German-speaking region in
      Europe. Until now, the DNEbM has initiated the development of curricula for EBM
      and health technology assessment (HTA) for undergraduate and continuing medical
      education. In addition, position papers regarding hot topics such as prostate
      cancer screening with PSA or registration of randomised controlled trials were
      published. The Network's HTA section comprises experts from universities,
      institutes, health care administration and industry. Currently, the HTA section
      is developing an Internet-based course for users and doers of HTA reports in
      Germany.

PMID- 16465519
TI  - [III. IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro 24-27 July
      2005. Part 2].

PMID- 16465518
TI  - [The role of randomised controlled trials in the medical evaluation of routine
      procedures].
AB  - If a demand exists for the evaluation of the favourable and adverse effects of a
      medical procedure, a comparison is required; this comparison should be fair. The
      only procedure that ensures a fair comparison is randomisation. Randomised
      controlled trials (RCTs) therefore represent the gold standard in the evaluation
      of medical procedures; the non-application of a randomisation process must be
      justified in detail in individual cases. Reasons presented for not conducting an
      RCT are mainly based on a misunderstanding of the term "randomisation". They may
      also be based on circumstances where the conduct of any simultaneous comparison
      is unsuitable (independent of the mode of allocation) or on situations where
      there is practically no hypothesis available for a comparison, or even for a
      study. These factors are taken into account by the current regulations valid in
      Germany on the approval of drugs and on the reimbursement eligibility of health
      care services by statutory health insurance.

PMID- 16465520
TI  - [Patients after prostatectomy. Psychiatric comorbidity, need for
      psychooncological treatment and quality of life].
AB  - BACKGROUND: Prostate carcinoma patients (PCP) with mental disorders suffer
      frequently from a decreased quality of life (QOL) and often need
      psychooncological treatment (PTN). To meet that need, the extent of treatment
      required should be determined and a reliable identification routine implemented.
      METHODS: A total of 103 PCP were interviewed with a validated instrument (SCID)
      during urological inpatient treatment to assess mental disorders of PTN, and
      questionnaires were administered to examine QOL (QLQ-C30) and mental stress
      (HADS); 17 doctors and 23 nurses assessed their patients' PTN. RESULTS: Twenty
      percent of the patients had a PTN which was identified by doctors and nurses in
      50% of the cases and by HADS in up to 84%. Even 1 year after treatment, the QOL
      of patients with PTN was diminished, while patients without recovered remarkably
      better. CONCLUSION: Patients with PTN should be detected as a matter of routine,
      e.g., using the HADS, and treated early.

PMID- 16465521
TI  - [Functional and oncological outcome of salvage prostatectomy of locally recurrent
      prostate cancer following radiation therapy].
AB  - BACKGROUND: Although technically challenging, salvage radical prostatectomy (SRP)
      for radiorecurrent prostate cancer (PCA) is an effective option in carefully
      selected patients and offers the chance for cure and long-term survival.
      Sometimes local progression of PCA with subvesical obstruction following
      radiation therapy requires radical cystoprostatectomy or bladder-preserving
      urinary diversion. We present our experience with salvage radical prostatectomy
      in a group of 28 consecutive patients. PATIENTS AND METHODS: Between January 2003
      and August 2005, 25 patients underwent radical salvage surgery for locally
      recurrent PCA following external beam radiation (n=14), high-dose brachytherapy
      (n=8), and low-dose brachytherapy (n=6). All men had biopsy-proved recurrent or
      persistent PCA associated with PSA progression following radiation therapy.
      Preoperative imaging studies included bone scintigraphy and computed tomography
      without evidence of metastatic disease. Of the 28 men, 11 (39%) presented with
      bothersome irritative voiding dysfunction and rectal discomfort. Life expectancy
      was >10 years in all cases. We analyzed preoperative symptoms, treatment
      associated morbidity, pathohistological findings, and functional and oncological
      outcome after a mean follow-up of 12.5 (2-29) months. RESULTS: SRP was performed
      in all cases without significant intra- and perioperative complications: no
      rectal lacerations or ureteral lesions were encountered and mean blood loss was
      520 (200-950) ml. A total of 21 (75%) men underwent SRP: in 4 cases radical
      cystoprostatectomy was necessary due to bladder neck infiltration and in 3 men
      SRP with bladder neck closure and continent appendicovesicostomy was performed
      due to preexisting urinary stress incontinence. All men with subvesical
      obstruction experienced significant relief of urgency and significant irritative
      voiding dysfunction following radical salvage surgery. Pathohistological analysis
      of the prostatectomy specimen revealed pT1-2b PCA in 19 (67.8%), pT3a/b PCA in 5
      (17.8%), and lymph node metastasis or positive surgical margins in 7% of the
      patients. Two patients demonstrated a pT0 despite positive preoperative biopsies,
      and 20% demonstrated a Gleason score 8-10. With regard to functional outcome, 25%
      of the men need 2-3 pads daily whereas 78% of the men are continent. After a mean
      follow-up of 12.5 (2-29) months, two patients with pT3b and pN1 status exhibit a
      PSA relapse. CONCLUSION: Salvage RP or RCx is a technically challenging but
      feasible surgical approach with curative intent for the treatment of locally
      recurrent PCA in well selected patients preventing significant local
      complications such as subvesical obstruction, ureteral obstruction, hematuria,
      and rectal infiltration. Surgery-associated morbidity and complications are low
      and not comparable to earlier series. The indication for salvage RP requires
      positive biopsy and negative imaging studies.

PMID- 16465522
TI  - [Translational research in renal cell cancer. Illustrated by the example of the
      vascular endothelial growth factor pathway].
AB  - For patients with metastatic renal cell cancer (RCC), therapeutic options after
      cytokine failure are rather limited. There is a considerable need to identify new
      substances for systemic therapy. Due to upregulation after the loss of a
      functional von Hippel Lindau gene product, the vascular endothelial growth factor
      (VEGF) pathway is a promising target for a molecular based therapy. Over the last
      few years, therapeutic agents have been developed which inhibit this pathway at
      various levels. Here, we provide an overview of the molecular background and
      currently used drugs which have entered clinical trials in the setting of
      metastatic RCC disease. Until now, the results from early clinical trials are
      very promising, however, the best schedule, dosage, potential combination
      regimens, as well as long time efficacy, are still to be determined.

PMID- 16465523
TI  - [Application of tissue microarrays for the diagnosis, prognosis and therapeutic
      decision making in renal cell carcinoma].
AB  - The tissue microarray technique (TMA) represents a powerful diagnostic "high
      throughput" tool to analyse DNA/RNA or protein alterations in large patient
      cohorts in a time and cost effective way. This review focuses on the clinical
      application of TMA in renal cell carcinoma in modern "translational" medicine-
      "from bench to bedside". In particular, the advantages of TMA for diagnosis,
      prognosis and decisions for therapy will be considered in relation to renal cell
      cancer.

PMID- 16465524
TI  - [Cytogenetic alterations in renal tumors. Applications for comparative genomic
      hybridization and fluorescence in situ hybridization].
AB  - The WHO classification of renal cell carcinomas (RCC) takes into account
      chromosomal alterations. New cytogenetic techniques such as comparative genomic
      hybridization (CGH) and fluorescence in situ hybridization (FISH) offer
      alternative methods to the classic cytogenetic banding technique. Clear cell
      (classic) RCC frequently show the loss of 3p. Papillary RCC are characterized by
      trisomies and tetrasomies as well as loss of the Y chromosome. CGH analysis
      demonstrates that DNA copy increase is more common in type I papillary RCC
      compared to type II. Chromophobe RCC are characterized by losses in chromosomes
      1, 2, 6, 10, 13, 17, and 21. Oncocytomas can be divided into cases with
      rearrangements in the 11q13 region and those with loss of chromosome 1 and the
      sex chromosomes. Translocations involving chromosome 3, such as
      t(3;8)(p14;q24.13) and t(2;3)(q35;q21) have been described in familial clear cell
      RCC. The most recent class of RCC, seen only in men, is referred to as
      translocation tumors. These tumors demonstrate a tubulopapillary growth pattern
      and have a t(X;1)(p11.2;q21.2) translocation. Although not required for most
      clinical diagnoses, CGH and FISH complement the standard histologic diagnosis of
      RCC and may provide a definitive diagnosis in a small number of challenging
      cases.

PMID- 16465525
TI  - [Microarrays for the identification of molecular markers in the diagnosis and
      therapy of renal cell carcinomas].
AB  - Within the framework of the large interdisciplinary projects in biology, in
      particular the human genome project, a variety of novel technologies with
      unprecedented value for the analysis of clinical issues have been developed. DNA
      microarrays are a prominent example of this: they are powerful tools to
      investigate global gene expression in tumors and their corresponding normal
      tissues, to classify tumors based on their molecular properties, and to identify
      novel targets for future tumor therapy. Here, we review recent results of global
      gene expression analyses in renal cell carcinoma and discuss their implications
      for the diagnosis, prognosis, and therapy of human cancer.

PMID- 16465528
TI  - Autologous control of a highly malignant syngeneic CRNK-16 leukemia in the rat: a
      role for NK cells.
AB  - It is unclear whether autologous immunity could be recruited to restrict the
      progression of leukemia. Patients harboring leukemia commonly display suppressed
      cell mediated immunity, which may contribute to their inability to control the
      disease. Immune response against leukemia is evident in allogeneic HLA-mismatched
      bone marrow transplantation, implicating the involvement of NK cells. This graft
      versus-leukemia (GVL) activity suggests that, if not suppressed, an autologous NK
      cell response could potentially control acute leukemia that had down-regulated
      HLA expression. In the current study we assessed the role of non-suppressed
      autologous NK cells in controlling a syngeneic highly malignant leukemia, the
      CRNK-16 line, that constitute a major cause of natural death in aged F344 rats. A
      minuscule dose of 60 CRNK-16 leukemia cells per rat was sufficient to induce 50%
      mortality rates, and animals that survived this challenge did not show improved
      survival upon a second challenge. The CRNK-16 line was found to exhibit low
      levels of MHC-I, and selective in vivo depletion of NK cells nullified in vitro
      NK activity against the CRNK-16 line and reduced survival rates from this
      leukemia. In vivo activation of NK cells, employing low doses of poly I-C or IL
      12, increased in vitro NK activity against the leukemia and dramatically improved
      survival rates when treatment was initiated before, but not after leukemia
      inoculation. These results indicate the ability of competent autologous NK cells
      to restrict highly malignant non-immunogenic leukemia. Thereby, this model
      presents an opportunity to study specific in vivo NK-leukemia interactions.

PMID- 16465526
TI  - Medical decision-making of the patient in the context of the family: results of a
      survey.
AB  - GOALS OF THE STUDY: From the perspective of patient autonomy, the family is often
      looked upon as a troublemaker in medical decision-making. The question remains
      open as to whether it is possible to do justice to the autonomy of the individual
      patient and to the claims of his family at the same time. PATIENTS AND METHODS: A
      clinical study was undertaken when both patients and dependents were interviewed.
      One hundred people (50 pairs) participated in this study and could be analyzed. A
      questionnaire consisting of 15 items was used and was evaluated to see if and how
      the attitudes concerning medical decision-making differ between patient and
      dependent. RESULTS: The majority of the interviewees (89%) agreed with the
      opinion that medical decisions should be made jointly by the patient, the family,
      and the doctor. Ninety-three percent approved of the claim to inform not only the
      patient, but also the family. Seventy percent of the patients and 54% of the
      dependents think that the family is entitled to have a say in matters concerning
      medical decision-making, only 30% of the patients, but 42% of the dependents
      argued against this view. Eighty-four percent of the patients argued against a
      change in this right at the end of life, which was approved by 32% of the family
      members. CONCLUSIONS: The family plays a central role in medical decision-making.
      This could be shown by a survey among patients with malignant diseases and their
      dependents. These initial findings must be verified in a larger population. The
      increased inclusion of the family in the process of medical decision-making
      corresponds in general to the expressed will of the patients. The model of shared
      decision-making is favored by values which both the family and the patient have
      in common. Thus, a family-based decision-making theory needs to be formulated in
      the future.

PMID- 16465529
TI  - Mechanisms of neurodegeneration in neuronal ceroid-lipofuscinoses.
AB  - Neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative diseases
      and autosomal recessive lysosomal storage disorders. We examined the involvement
      of cell death, oxidative stress, and glutamate excitotoxicity using
      immunohistochemistry against Bcl-2, Bcl-x, oxidative products to proteins, lipids
      and DNA, calcium-binding proteins (calbindin-D28K, parvalbumin, calretinin), and
      glial glutamate transporters (excitatory amino acid transporters 1 and 2), in
      addition to terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling
      (TUNEL) in the brains from three cases of late infantile form of NCL (LINCL) and
      one case of juvenile form of NCL (JNCL) to investigate the neurodegenerative
      mechanisms. In the cerebral and cerebellar cortex, all of three LINCL cases
      demonstrated neurons with TUNEL-immunoreactive nuclei, whereas the JNCL case did
      not show TUNEL-immunoreactive nuclei. The coexistence of the nuclear TUNEL
      immunoreactivity nuclei and cytoplasmic deposition of 4-hydroxy-2-nonenal
      modified protein in the frontal cortex and hypoglossal nucleus may suggest a
      possible interrelationship between DNA fragmentation and lipid oxidation in
      LINCL. Additionally, glycoxidation of protein and oxidative stress to DNA seemed
      to be involved in the cerebellar and cerebral degeneration, respectively.
      Interneurons immunoreactive for calbindin-D28K and parvalbumin were severely
      reduced in the cerebral cortex, whereas those for calretinin were comparatively
      well preserved in LINCL, indicating the possibility of altered GABAergic system.
      The disturbance of expression of glial glutamate transporters seemed to be
      heterogeneous and mild. These findings suggest the possibility of new treatments
      for neurodegeneration in LINCL using antioxidative agents and/or GABAergic
      medications.

PMID- 16465530
TI  - Cranial fasciitis with exclusive intracranial extension in an 8-year-old girl.

PMID- 16465531
TI  - Cortical areas functionally linked with the cerebellar second homunculus during
      out-of-phase bimanual movements.
AB  - We used functional magnetic resonance imagery (fMRI) to study cortical activation
      during index finger-thumb opposition of both hands using in-phase and out-of
      phase modes. In-phase movements activated the sensorimotor cortex. During out-of
      phase movements, activations were also observed in the supplementary motor area
      (SMA), in the cingulate motor area (CMA) and, less frequently, in the anterior
      cingulate cortex (ACC). As we have previously shown and confirmed in the present
      study, the same out-of-phase bimanual movements specifically activate the
      cerebellar second homunculus, leading us to postulate that the cerebellar second
      homunculus and medial wall motor areas participate in a circuit specifically
      involved in timing complex movements.

PMID- 16465534
TI  - The effect of subcutaneously injected nicotine on achilles tendon healing in
      rabbits.
AB  - The objective of this study was to evaluate the effect of subcutaneously injected
      nicotine on transversely transected and sutured achilles tendon healing in an
      experimental rabbit model. Adult New Zealand rabbits (n=22) weighting 3,000-3,500
      g were used in this experimental study. Rabbits were randomly divided into two
      groups. Achilles tendon was transversely incised and repaired in all animals. In
      the experiment group subcutaneous injection of Nicotine tartrate 3 mg/kg/day was
      done. In the control group Serum physiologic injection was done at the same
      dosage. The injections were made three times a day in equal dosages. Nicotine and
      SF injections were made until the end of the 8-week, and then all animals were
      euthanized. Both light microscopic and electron microscopic evaluations were made
      on 14 animals. In N group light microscopic evaluation showed a visible gap in
      repair site. The total tendon score represented in N group was less than in SF
      group. The statistical analysis of the groups was significantly different for
      total tendon scores (P=0.002). Beside this electron microscopic examination
      showed inactive and degenerated fibroblasts and irregular collagen fibrils around
      them as well as collagen synthesis interruption in N group. Biomechanical
      evaluation was made on eight animals. The average tensile strength values in
      Group N (139.47+/-44.55 N) were significantly lower than those in Group SF
      (265.9+/-39.01 N) (z=2.309, P=0.029). Nicotine is the major chemical component
      common to all cigarettes and previously has been shown to affect wound and
      fracture healing adversely. The results of this study show that nicotine impairs
      achilles tendon healing after a surgical repair.

PMID- 16465535
TI  - Reconstruction of a chronic quadriceps tendon tear in a body builder.
AB  - Chronic quadriceps tendon tears are uncommon. We report about a body builder
      taking a cocktail of anabolic drugs for several years in whom reconstruction of a
      chronic quadriceps tendon tear was performed using ipsilateral hamstring tendons
      with good results despite the 7 month delay between injury and surgery. The use
      of hamstring tendons is a good option for the management of these lesions.

PMID- 16465536
TI  - Accuracy of needle placement in ACJ injections.
AB  - Localization of the Acromioclavicular joint (ACJ) even at arthroscopic surgery
      may be difficult because of its small size, osteophytes, variable anatomy of the
      joint and capsule. Therefore injection of the ACJ in the clinic may well be
      inaccurate. The aim of this study was to review the clinical accuracy of needle
      placement in ACJ injections, if performed without the aid of image
      intensification. Sixty patients with 66 shoulders were injected in the Day Unit
      in our department. The joint was palpated clinically, and the needle was placed
      in the site thought to be in the AC Joint. An image intensifier was then used to
      check the position of the needle in the AP and axillary views. The needle was
      considered correctly placed if between the bony boundaries of the acromion and
      clavicle. This was found in only 26 injections (39.4%). The remaining 40
      injections (60.6%) were misplaced, either laterally in 21 injections (31.8%),
      medially in 13 (19.8%), anteriorly in 3 (4.5%) and inferiorly in 3 injections
      (4.5%). Theses were then reinserted under image intensifier guidance. The
      misplaced injections would have lead to inaccurate clinical outcomes, and
      decision making. This study is similar to other studies in that X-ray guidance
      improves the accuracy of injections and surgery. However the potential error rate
      for the small, anatomically variable AC joint is high. There is a 60% potential
      for ACJ injections to be out of the joint if performed by palpation alone, and we
      recommend the routine use of image intensification guidance.

PMID- 16465537
TI  - Prospective randomized clinical comparison of femoral transfixation versus
      bioscrew fixation in hamstring tendon ACL reconstruction--a preliminary report.
AB  - PURPOSE: The purpose of this study is to clinically evaluate hamstring tendon
      anterior cruciate ligament (ACL)-reconstruction using femoral fixation with
      bioresorbable interference screws and with a bioresorbable transfixation device.
      HYPOTHESIS: The ACL-reconstruction using the transfixation device at the femoral
      side leads to less knee laxity and therefore to a better clinical outcome for the
      patient. TYPE OF STUDY: Prospective randomized clinical outcome study. METHODS:
      From February 2002 to December 2002, a total of 68 patients with hamstring ACL
      reconstruction using a femoral fixation once with TransFix (n=38; m:22 and f:16;
      median age=28.5 range 15-47) and the second with bioscrew (BS) (n=30; m:20, f:10;
      median age=25.5 range 13-61) completed the follow-up period. Patients in each
      group got a clinical assessment at 3, 6, and 12 months after surgery. The
      measurement of anterior translation of the tibia has been performed using the
      Rolimeter device. RESULTS: No significant differences in the knee laxity testing
      using the Rolimeter device were seen between both groups and over time within
      these groups. Ninety percent of all patients had functionally normal or near
      normal International Knee Documentation Committee (IKDC) knee ligament ratings.
      The TF-group included 17 grade A, 19 grade B, and 2 grade C knees, and the BS
      group had 12 grade A, 13 grade B, and 5 grade C knees. The IKDC rating, the OAK
      score, the Tegner-activity-score, and the Lysholm-score did not show significant
      differences between the TF-group and the BS-group. CONCLUSION: We disproved our
      hypothesis that the transfixation technique leads to less laxity and therefore to
      a better clinical outcome when compared to the use of BS. The clinical results in
      this study clarified that this technique is an effective and safe method for
      femoral hamstring fixation in ACL-reconstruction. However, this technique
      revealed no advantage compared to the bioscrew fixation technique within the
      short-term follow-up.

PMID- 16465538
TI  - Sonographic prenatal diagnosis of malpositioned stomach as a feature of
      uncomplicated intestinal malrotation.
AB  - Intestinal malrotation is a developmental anomaly affecting the position and
      peritoneal attachments of the small and large intestines during fetal life. Most
      often the diagnosis is established in the first year of life on the basis of
      abdominal pain and bile-stained vomiting secondary to bowel obstruction. The
      antenatal diagnosis can be suggested by identification of the complications such
      as bowel dilatation, ascites or meconium peritonitis. We describe two cases of
      isolated antenatal gastric malposition without any other associated anomaly that
      were confirmed after birth to be due to intestinal malrotation. We suggest that
      such an antenatal finding should alert the paediatrician to close clinical follow
      up and prompt the diagnosis and surgical treatment in case of abdominal pain
      and/or bilious vomiting.

PMID- 16465540
TI  - Colchicine in experimental alkaline burns of the rat esophagus: an old drug, a
      new indication?
AB  - AIM: An experimental study was performed to investigate the efficacy of
      colchicine in the prevention of fibrosis in the alkaline burn of the esophagus in
      rats. METHOD: A standard esophageal alkaline burn was produced by the application
      of 37.5% NaOH for a period of 90 s to the distal esophagus followed by a water
      rinse. The experiments were conducted twice with two different dosages of
      colchicine. In the first experiment, colchicine 1 mg/kg (i.p.) was applied once,
      on the first day. Group A (n:8), the sham laparotomy group; group B (n:8), the
      untreated group (positive control group); Group C (n:16), where the standard
      esophageal burn was induced and colchicine applied at a dose of 1 mg/kg i.p. in 1
      ml volume, and group D (n:14), where the rats did not have any operation, but
      were treated with colchicine (1 mg/kg, i.p.) as in group C. In the second
      experiment, colchicine was applied at repeated doses of 100 microg/kg (i.p.) on
      the first, 7th, 14th, and 21st days. Twenty-five rats were divided into groups.
      Group AA (n:8), the sham laparotomy group; group BB (n:9), the untreated group
      (positive control group); and group CC (n:8), where the standard esophageal burn
      was induced and colchicine was applied at repeated doses. All the rats were
      killed on the 28th day and evaluated for esophageal tissue hydroxyproline content
      and histopathologic damage score. RESULTS: Colchicine treatment at a dose of 1
      mg/kg significantly reduced the quantity of hydroxyproline in the esophageal
      tissue in groups C and D compared with the positive control group B (P < 0.05).
      However, it is associated with a mortality rate of 60%. Colchicine at repeated
      doses of 100 microg/kg showed no significant effect in group CC compared to the
      untreated group BB and in the quantity tissue of hydroxyproline content (P >
      0.05). CONCLUSION: At non-toxic doses, colchicine was not effective in the
      treatment of alkaline esophageal burn in rats. Colchicine-like molecules with
      less adverse effects or colchicine itself in titrated doses may be hopeful in
      preventing the development of fibrosis in the alkaline burns of the esophagus.

PMID- 16465539
TI  - Congenital hearing impairment.
AB  - Establishing the etiology of congenital hearing impairment can significantly
      improve treatment for certain causes of hearing loss and facilitates genetic
      counseling. High-resolution CT and MRI have contributed to the evaluation and
      management of hearing impairment. In addition, with the identification of
      innumerable genetic loci and genetic defects involved in hearing loss, genetic
      testing has emerged as an invaluable tool in the assessment of hearing
      impairment. Some of the common forms of congenital hearing loss are reviewed and
      their imaging features illustrated.

PMID- 16465541
TI  - Changes in stable isotopic signatures of soil nitrogen and carbon during 40 years
      of forest development.
AB  - Understanding what governs patterns of soil delta15N and delta13C is limited by
      the absence of these data assembled throughout the development of individual
      ecosystems. These patterns are important because stable isotopes of soil organic
      N and C are integrative indicators of biogeochemical processing of soil organic
      matter. We examined delta15N of soil organic matter (delta15NSOM) and delta13CSOM
      of archived soil samples across four decades from four depths of an aggrading
      forest in southeastern USA. The site supports an old-field pine forest in which
      the N cycle is affected by former agricultural fertilization, massive
      accumulation of soil N by aggrading trees over four decades, and small to
      insignificant fluxes of N via NH3 volatilization, nitrification, and
      denitrification. We examine isotopic data and the N and C dynamics of this
      ecosystem to evaluate mechanisms driving isotopic shifts over time. With forest
      development, delta13CSOM became depth-dependent. This trend resulted from a
      decline of approximately 2 per thousand in the surficial 15 cm of mineral soil to
      -26.0 per thousand, due to organic matter inputs from forest vegetation. Deeper
      layers exhibited relatively little trend in delta13CSOM with time. In contrast,
      delta15NSOM was most dynamic in deeper layers. During the four decades of forest
      development, the deepest layer (35-60 cm) reached a maximum delta15N value of 9.1
      per thousand, increasing by 7.6 per thousand. The transfer of > 800 kg ha(-1) of
      soil organic N into aggrading vegetation and the forest floor and the apparent
      large proportion of ectomycorrhizal (ECM) fungi in these soils suggest that
      fractionation via microbial transformations must be the major process changing
      delta15N in these soils. Accretion of isotopically enriched compounds derived
      from microbial cells (i.e., ECM fungi) likely promote isotopic enrichment of
      soils over time. The work indicates the rapid rate at which ecosystem development
      can impart delta15NSOM and delta13CSOM signatures associated with undisturbed
      soil profiles.

PMID- 16465542
TI  - Solar furnaces or swamp coolers: costs and benefits of water use by solar
      tracking flowers of the alpine snow buttercup, Ranunculus adoneus.
AB  - Solar tracking or heliotropism simultaneously raises organ temperature and light
      interception. For leaves and flowers carbon gain is maximized at the expense of
      water loss. In this study I explore how costs and benefits associated with water
      use by solar-tracking flowers of the alpine snow buttercup, Ranunculus adoneus
      change with ambient temperature. First, I test whether heliotropism increases the
      water cost of reproduction in the snow buttercup under extant alpine conditions.
      I then explore whether water use for evaporative cooling in solar-tracking
      flowers reduces the risk of over-heating as temperatures increase. Solar
      tracking, by elevating floral temperature and irradiance causes a 29% increase in
      water uptake by flowers. Gas exchange measurements suggest that the extra water
      taken up by solar-tracking flowers is released through transpiration.
      Transpirational cooling in turn allows solar-tracking flowers to gain advantages
      of enhanced light interception and warmth while reducing the risk of over
      heating. Transpiration reduces excess temperature in solar-tracking flowers, but
      at a water cost. Results show that even in cool alpine habitats, flower
      heliotropism has water costs to balance its reproductive advantages. Plants with
      solar-tracking flowers may tolerate hotter conditions if soil moisture is
      plentiful, but not under drought.

PMID- 16465544
TI  - The tumor specific cytotoxicity of dihydronitidine from Toddalia asiatica Lam.
AB  - PURPOSE: In recent years, a number of reports have shown the anticancer activity
      of plant extracts and phytoalkaloid. METHODS: We have evaluated the cytotoxicity
      profiles of 157 extracts prepared from dietary or medical plants growing in the
      Okinawa island, using 10 different cell lines. In vitro cytotoxicity screening
      indicated the presence of a highly selective cytotoxic compound in the extract of
      Toddalia asiatica Lam. The known alkaloid (1,3)benzodioxolo(5,6-c)phenanthridine,
      12,13-dihydro-2,3-dimethoxy-12-methyl-(dihydronitidine) was identified as an
      active material from this plant. This alkaloid had highly specific cytotoxicity
      to human lung adenocarcinoma (A549) cells. RESULTS: The results of the
      fluorescence activated cell sorter (FACS) analysis and the measurement of caspase
      3 activity showed that dihydronitidine induced specific apoptotic cell death in
      A549 cells. Gene expression analysis in the apoptotic cells found that
      dihydronitidine variously regulated the cell cycle related genes (CDK2 and CCNE),
      and up-regulated the cell death related genes specifically in tumor cells. Thus
      dihydronitidine manifested its characteristics in the tumor selective
      cytotoxicity, contrasting with the case of a known anticancer agent camptothecin
      (CPT). Microscopic observation further revealed the specific accumulation of
      dihydronitidine within the cytosolic organelle, but not in the nuclei of
      adenocarcinoma. No accumulation was observed with CPT in all cell lines.
      CONCLUSION: The data suggested that dihydronitidine toxicity targeted a
      particular intracellular organelle in the tumor cells.

PMID- 16465545
TI  - Population analysis of the pharmacokinetics and the haematological toxicity of
      the fluorouracil-epirubicin-cyclophosphamide regimen in breast cancer patients.
AB  - PURPOSE: The aims of the study were (a) to characterise the pharmacokinetics
      (PK), including inter-individual variability (IIV) and inter-occasion variability
      (IOV) as well as covariate relationships and (b) to characterise the relationship
      between the PK and the haematological toxicity of the component drugs of the
      fluorouracil (5-FU)-epirubicin (EPI)-cyclophosphamide (CP) regimen in breast
      cancer patients. PATIENTS AND METHODS: Data from 140 breast cancer patients,
      either within one of different studies or in routine clinical management, were
      included in the analyses. The patients were all treated with the fluorouracil
      epirubicin-cyclophosphamide (FEC) regimen every third week for 3-12 courses,
      either in standard doses, i.e. 600/60/600 mg/m(2) of 5-FU, EPI and CP,
      respectively, or according to a dose escalation/reduction protocol (tailored
      dosing). PK data were available from 84 of the patients, whereas time-courses of
      haematological toxicity were available from 87 patients. The data analysis was
      carried out using mixed effects models within the NONMEM program. RESULTS: The PK
      of 5-FU, EPI and 4-hydroxy-cyclophosphamide (4-OHCP), the active metabolite of
      CP, were described with a one-compartment model with saturable elimination, a
      three-compartment linear model and a two-compartment linear model, respectively.
      No clinical significant correlation was found between PK across drugs. The
      unexplained variability in clearance was found to be less within patients,
      between courses (inter-occasion variability, IOV) than between patients (inter
      individual variability, IIV) for EPI and 5-FU. For 4-OHCP, however, the IIV
      diminished by approximately 45% when significant covariates were included and the
      final population model predicts an IIV that is equal to IOV. Significant
      covariates for elimination capacity parameters were serum albumin (5-FU, EPI and
      4-OHCP), creatinine clearance (5-FU), bilirubin (EPI) and body surface area (BSA)
      (4-OHCP). Elimination capacity of 5-FU and EPI was not related to BSA and for
      none of the studied drugs did body weight explain the PK variability. The time
      course of haematological toxicity after treatment was well described by a semi
      physiological model that assumes additive haematological toxicity between CP and
      EPI with negligible contribution from 5-FU. The influence of G-CSF could be
      incorporated into the model in a mechanistic manner as shortening the maturation
      time to 43% of the normal duration and increasing the mitotic activity to 269% of
      normal activity. CONCLUSIONS: The models presented describe the dose
      concentration-toxicity relationships for the FEC therapy and may provide a basis
      for implementation and comparison of different individualisation strategies based
      on covariates, therapeutic drug monitoring and/or pharmacodynamic (PD) feedback.
      The PD model extends on previous semi-mechanistic models in that it also takes G
      CSF administration into account.

PMID- 16465543
TI  - [Injuries to the craniocervical junction].
AB  - Injuries to the upper cervical spine (C0-C2) play a major role in surgical
      treatment of traumatic sequelae in the entire cervical spine. Even though the
      number of such operations has increased in recent years, there are no clear
      treatment recommendations for most types of cervical spine injuries. In view of
      the wide range of injury types and the correspondingly large number of treatment
      options, this review focuses mainly on the following types of injuries: C0
      fractures, occipital condyle fractures (OCF), atlanto-occipital dislocation
      (AOD), atlas fractures, atlantoaxial dislocation (AAD), and axis fractures.
      Important aspects of the mechanisms of injury, clinical signs and symptoms,
      diagnostic procedures, and treatment options are discussed. Special emphasis is
      placed on comparatively reviewing the different treatment options discussed in
      the literature. A summary in table form is presented at the end of each chapter
      for quick reference.

PMID- 16465546
TI  - The properties of recombinant Sendai virus having the P gene of Sendai virus pi
      strain derived from BHK cells persistently infected with Sendai virus.
AB  - We prepared the chimeric recombinant Sendai virus [rSeV(Ppi)] by replacing the P
      gene of the Z strain with that of pi strain for analyzing the function of Ppi,
      Vpi and Cpi proteins. Intriguingly, HA production by rSeV(Ppi) is significantly
      lower at 38 degrees C than at 32 degrees C, showing that virus growth of
      rSeV(Ppi) is slightly suppressed at 38 degrees C. However, the main phenotypes of
      SeVpi, a marked temperature sensitivity as viral replication and an ability of
      establishing persistent infection, are not explained by the Ppi, Vpi and Cpi
      proteins. The V and C proteins form inclusion bodies in L929 cells infected with
      rSeV(Ppi) and incubated at 38 degrees C. L929 cells infected with rSeV(Ppi) and
      L929 cells stably expressing the Cpi protein show resistance to interferon-beta
      at 32 and 38 degrees C, indicating that the Cpi protein per se is not temperature
      sensitive to inhibition of IFN signaling. The complete genome sequences of Sendai
      virus (SeV) pi and parent Nagoya strains were determined. Fifty nucleic acid
      substitutions are found in the genome sequence of SeV pi strain in comparison
      with Nagoya strain. There are three nucleic acid substitutions in the leader
      sequence, while the trailer, intergenic, gene-end and gene-start sequences of
      both strains are completely identical. Deletions and insertions of nucleotide are
      not found. There are 32 amino acid substitutions in Sendai virus pi strain. The
      specific amino acid substitutions unique to the SeVpi are 18. Information about
      the complete genome sequences of SeVpi strain is important to totally understand
      the persistent infection and lower pathogenicity of SeV.

PMID- 16465547
TI  - Evidence that the rabbit proton-peptide co-transporter PepT1 is a multimer when
      expressed in Xenopus laevis oocytes.
AB  - To test whether the rabbit proton-coupled peptide transporter PepT1 is a
      multimer, we have employed a combination of transport assays, luminometry and
      site-directed mutagenesis. A functional epitope-tagged PepT1 construct (PepT1
      FLAG) was co-expressed in Xenopus laevis oocytes with a non-functional but
      normally trafficked mutant form of the same transporter (W294F-PepT1). The amount
      of PepT1-FLAG cRNA injected into the oocytes was kept constant, while the amount
      of W294F-PepT1 cRNA was increased over the mole fraction range of 0 to 1. The
      uptake of [(3)H]-D: -Phe-L: -Gln into the oocytes was measured at pH(out) 5.5,
      and the surface expression of PepT1-FLAG was quantified by luminometry. As the
      mole fraction of injected W294F-PepT1 increased, the uptake of D: -Phe-L: -Gln
      decreased. This occurred despite the surface expression of PepT1-FLAG remaining
      constant, and so we can conclude that PepT1 must be a multimer. Assuming that
      PepT1 acts as a homomultimer, the best fit for the modelling suggests that PepT1
      could be a tetramer, with a minimum requirement of two functional subunits in
      each protein complex. Western blotting also showed the presence of higher-order
      complexes of PepT1-FLAG in oocyte membranes. It should be noted that we cannot
      formally exclude the possibility that PepT1 interacts with unidentified Xenopus
      protein(s). The finding that PepT1 is a multimer has important implications for
      the molecular modelling of this protein.

PMID- 16465548
TI  - Two recessive genes controlling thermophotoperiod-sensitive male sterility in
      wheat.
AB  - Male sterility of wheat-breeding line 337S (Triticum aestivum L.) is sensitive to
      both short day-length/low temperature and long day-length/high temperature. 337S
      was crossed with the common wheat variety, Huamai No. 8 and the F1 was highly
      fertile. The F2 population segregated in a 15:1 ratio for fertility/sterility in
      243 individuals under long day-length/high-temperature. The two thermophotoperiod
      responsive male sterile genes were mapped to chromosomes 5B and 2B using Simple
      Sequence Repeat (SSR) markers and bulked segregant analysis. Partial linkage maps
      around the sterility loci of chromosomes 2B and 5B were constructed using the 243
      individuals in the F2 population. One gene (wptms1) for male sterility was
      flanked by the SSR markers Xgwm335 and Xgwm371 at a genetic distance in
      chromosome 5B of 4.1 and 24.4 cM, respectively. The second gene (wptms2) was
      mapped between markers Xgwm374 and Xgwm120 at a genetic distance of 6.6 and 20.9
      cM, respectively. The closest linked markers Xgwm335 (wptms1) and Xgwm374
      (wptms2) explained 53 and 38% of phenotypic variation for the fertility. The SSR
      markers provide a useful tool to transfer the male sterile genes into elite wheat
      germplasm.

PMID- 16465549
TI  - Impact of plant breeding on genetic diversity of the Canadian hard red spring
      wheat germplasm as revealed by EST-derived SSR markers.
AB  - Genetic diversity changes in wheat germplasm have been studied using different
      molecular markers, but little is known about the impact of plant breeding on the
      transcribed segments of the wheat genome. The objective of this study was to
      assess diversity changes in 75 Canadian hard red wheat cultivars released from
      1845 to 2004 using 37 EST-derived microsatellite (eSSR) markers. These markers
      were derived from at least 19 transcribed sequences with putative functions
      assigned and sampled 17 wheat chromosomes. A total of 138 eSSR alleles was
      detected, and their allelic frequencies ranged from 0.01 to 0.99 with an average
      of 0.41. Allelic counts were significantly reduced at three loci for cultivars
      released after 1990. Sixteen alleles at 14 loci in pre-1910 cultivars were lost
      in cultivars released after 1990. The lost alleles had frequencies ranging from
      0.03 to 0.17 and averaging 0.07. Partitioning the eSSR variation showed the four
      ancestral families accounted for 14.7% of the variation, followed by the six
      breeding periods with 12.8% and the eight breeding programs with 5.8%. A genetic
      shift was observed in the cultivars released over the six breeding periods,
      reflecting the various breeding efforts. These results illustrate the impact of
      the Canadian wheat breeding on the transcriptional segments of the wheat genome.
      These findings, along with those from genomic SSR markers, suggest the Canadian
      wheat breeding programs have reduced genetic diversity in the hard red spring
      wheat.

PMID- 16465550
TI  - Improved discrimination of breast lesions using selective sampling of segmented
      MR images.
AB  - OBJECTIVE: The aim of this work is to examine if the specificity of
      differentiation between malignant and benign tumours can be improved by
      retrospectively examining lesion-extracted distributions. A semi-automated method
      for selecting a region-of-interest (ROI) is described. A new histogram
      segmentation approach for sampling pharmacokinetic breast maps of transfer uptake
      is defined in order to assign classification variables for the lesion. METHOD:
      Fifty exchange rate parameter maps were extracted from 49 subjects and
      retrospectively analysed. Distributions obtained from semi-automatically
      delineated ROIs were subdivided into ten overlapping segments. Parameters were
      extracted from each segment which effectively presents a new pixel intensity
      sampling strategy. Mann-Whitney non-parametric tests and ROC curves were
      generated. RESULTS: Correlation exists between mean parameter values drawn from
      semi-automatically or manually drawn ROIs. However, the former yield higher
      specificity values as applied to this subset of enhancing benign lesions.
      Segmenting the exchange rate parameter histogram allows the identification of
      which part of the distribution correlates most with tumour type. Significant
      improvement in specificity is obtained when using half the pixels within the ROI.
      CONCLUSION: Improved specificity values are obtained by a new method of selecting
      the differentiation parameters which relies on intensity rather than spatial
      segmentation. Only half the pixels available within the ROI contributed to the
      measured classification parameters.

PMID- 16465551
TI  - [HME filter versus patient-related replacement of tubes from the ventilation
      circuit for anaesthesia: a cost-benefit analysis].
AB  - Procedure-related costs were calculated for an operating theatre with 10
      operating rooms. The variable parameter was the different hygiene regimens for
      the preparation of the anaesthesia circuit. In April 2003 a change was made for
      the whole anaesthesia area. Either change of the anaesthesia tube system after
      every patient or the use of a hydrophobic HME-F (heat and moisture exchange
      filter) with daily or weekly change of the anaesthesia tube system were
      calculated. All costs were ascertained on real findings and typical procedures.
      Data according to safety and hygienic value were discussed and supplemented by
      our own findings about perioperative pneumonia. The additional costs for the HME
      F are covered by the savings for CO(2) lines and the reduction of reprocessing
      expenses and overall material costs were reduced. The operational work on
      anaesthesia machines decreased considerably. Combined cost types revealed savings
      up to 9,72 EUR for a single anaesthesia procedure. Filtration of the respiratory
      gases for particles, bacteria, viruses and airway climatisation is an additional
      positive effect of HME-F use. Incidence of postoperative pneumonia on intensive
      care units was monitored by KISS (German hospital infection surveillance system)
      and the change to the HME-F regimen did not indicate a higher risk of infection.
      By the implementation of a weekly change of the anaesthesia tube system using HME
      filters a hygienic management for anaesthesia circuit reprocessing was found
      which could mobilize considerable resources.

PMID- 16465552
TI  - A five-week-old girl with inspiratory stridor due to infantile
      hemangiopericytoma.
AB  - A 5-week-old girl with inspiratory stridor is presented. No immediate cause of
      the stridor was found, but eventually a diagnosis of infantile hemangiopericytoma
      located in the rhinopharynx was made. After surgery all respiratory symptoms
      disappeared. CONCLUSION: Infantile hemangiopericytoma is a rare tumour of infancy
      and a very rare cause of inspiratory stridor in this age group. The mainstay of
      treatment is surgery. The overall prognosis is favourable but because of the
      unpredictable nature of the tumour, long-term follow-up is recommended.

PMID- 16465553
TI  - Reliability and validity of the National Institutes of Health: Chronic
      Prostatitis Symptom Index in a Malaysian population.
AB  - The objective of the study is to determine the short- and long-term utility of
      the Chinese, Malay and English versions of the National Institutes of Health-
      Chronic Prostatitis Symptom Index (NIH-CPSI) in our ethnically diverse
      population. The NIH-CPSI was translated into Chinese and Malay, and then verified
      by back translation into English. Subjects included 100 new chronic
      prostatitis/chronic pelvic pain (CP/CPPS) patients, 71 new benign prostatic
      hyperplasia patients and 97 healthy individuals. Reliability was evaluated with
      test-retest reproducibility (TR) by calculating intraclass correlation
      coefficients (ICC). Internal consistency was evaluated by calculating Cronbach's
      alpha (alpha). Validity assessments included discriminant and construct validity.
      (Presented in the order of Chinese, Malay then English). ICC values for short
      term (1 week) TR were 0.90, 0.80 and 0.89, while ICC values for long-term (14
      weeks) TR were 0.54, 0.61 and 0.61. Cronbach's alpha values were 0.63, 0.62 and
      0.57. The NIH-CPSI total score discriminated CP/CPPS patients (P<0.001) from the
      control groups with receiver operating curve values of 0.95, 0.98 and 0.94,
      respectively. Construct validity, reflected by the correlation coefficient values
      between the International Prostate Symptom Score and the NIH-CPSI of CP/CPPS
      patients were 0.72, 0.49 and 0.63 (all P<0.05). The Chinese, Malay and English
      versions of the NIH-CPSI each proved effective in our population. Short-term TR
      and discriminant validity were excellent for all three versions. However, long
      term TR was only moderate, which might reflect variation in patients' perceptions
      of symptoms over time.

PMID- 16465554
TI  - Retroperitoneal gas gangrene after colonoscopic polypectomy without bowel
      perforation in an otherwise healthy individual: report of a case.
AB  - BACKGROUND: Abdominal gas gangrene caused by clostridia species is rare and
      usually associated with organ perforation, immune suppression, or advanced
      malignoma. CASE REPORT: A 61-year-old man was admitted with severe back pain 1
      day after uncomplicated colonoscopic polypectomy. With the exception of
      preexisting minor depression, the patient had been previously in excellent
      health. The computed tomography scan showed retroperitoneal emphysema in the left
      psoas muscle. During exploratory laparotomy, a spreading retroperitoneal phlegmon
      with pneumoretroperitoneum and a secondary peritonitis were found. A macroscopic
      perforation of the gut, particularly at the polypectomy sites was excluded. After
      the operation, the patient evolved in a septic shock condition and had pulmonary
      failure. Before hyperbaric oxygen therapy could be employed, the patient died.
      The autopsy showed a massive gas gangrene of the retroperitoneum caused by
      Clostridium perfringens, but no macroscopic bowel perforation was detected.
      RESULTS: This is the first report of a case of gas gangrene after uncomplicated
      polypectomy without macroscopic perforation in an otherwise healthy individual. A
      microperforation due to mucosal defect after polypectomy was most likely the
      entry point for the bacteria. CONCLUSION: We conclude that clostridial
      myonecrosis should be considered in unclear abdominal infections, even if the
      patient's history is not typical as in the present case.

PMID- 16465555
TI  - Pure intramedullary spinal cord metastasis secondary to gastric cancer.
AB  - Pure intramedullary spinal-cord metastases (ISCM) are a rare manifestation of
      cancer. We report a case of ISCM from gastric cancer. A 68-year-old man, treated
      with total gastrectomy for a gastric cancer, presented 9 months later with
      paresis of the left arm, pain and dissociated sensory loss. Magnetic resonance
      imaging revealed a pure intramedullary lesion at the C3-C5 level. After surgical
      resection, pathological findings revealed an undifferentiated adenocarcinoma of
      gastric origin. To our knowledge, this is only the second report of ISCM from
      gastric cancer in the literature.

PMID- 16465557
TI  - Effect of acute exposure to malathion and lead on sprint performance of the
      western fence lizard (Sceloporus occidentalis).
AB  - There are few ecotoxicological studies involving reptiles, despite the fact that
      anthropogenic pollutants have been identified as a major threat to reptile
      populations worldwide. Particularly lacking are effects-based studies in reptiles
      exposed to known concentrations of contaminants. We hypothesized that acute
      exposure to neurotoxic metals and pesticides could influence locomotor
      performance of reptiles. To test this hypothesis, we exposed western fence
      lizards (Sceloporus occidentalis) to two common and widely studied neurotoxic
      contaminants, malathion and lead (Pb). Single doses were administered via oral
      gavage at order-of-magnitude levels ranging from 0.2 to 200 and 1.0 to 1,000
      mg/kg (body weight basis) for malathion and Pb, respectively. Lizard sprint
      velocity was determined using a 2.3-m sprint track interfaced with a laptop
      computer 24 hrs prior to dosing and again at 4, 24, 120, and 312 hrs post-dose.
      Twenty percent and 30% mortality occurred at the highest malathion and Pb dose
      levels (200 and 1000 mg/kg) and 70% of the lizards exposed to 200 mg/kg malathion
      exhibited clinical symptoms of organophosphate poisoning. Contrary to our
      predictions, exposure to Pb had no effect on locomotor performance, and exposure
      to the highest concentration of malathion increased sprint velocity. Based on the
      fact that the lower and most ecologically relevant concentrations of Pb and
      malathion had no effect on sprint velocity, we suggest that other performance
      parameters that require fine locomotor skills (e.g., climbing ability) may be
      more sensitive metrics of acute neurotoxicity and warrant further study.

PMID- 16465558
TI  - Interfollicular fibrosis in the thyroid of the harbour porpoise: an endocrine
      disruption?
AB  - Previous studies have described high levels of polychlorobiphenyls (PCB),
      polybrominated diphenylether (PBDE), toxaphene, p,p'
      dichlorodiphenyltrichloroethane (DDT), and p,p'-dichlorodiphenyldichloroethylene
      (DDE) in the blubber of the harbour porpoise from the North Sea raising the
      question of a potential endocrine disruption in this species. In the present
      study, the thyroids of 57 harbour porpoises from the German and Danish (North and
      Baltic Seas), Norwegian, and Icelandic coasts have been collected for
      histological and immunohistological investigations. The number of follicles and
      the relative distribution of follicles, connective, and solid tissues (%) were
      quantified in the thyroid of each individual. Then, the potential relationship
      between the thyroid morphometry data and previously described organic compounds
      (namely, PCB, PBDE, toxaphene, DDT, and DDE) was investigated using factor
      analysis and multiple regressions. Thyroid morphology differed strongly between
      sampling sites. Porpoises from the German (North and Baltic Seas) and Norwegian
      coasts displayed a high percentage of connective tissues between 30 and 38%
      revealing severe interfollicular fibrosis and a high number of large follicles
      (diameter>200 microm). A correlation-based principal component analysis (PCA)
      revealed two principal components explaining 85.9% of the total variance. The
      variables PCB, PBDE, DDT, and DDE compounds loaded highest on PC1 whereas
      toxaphene compound loaded most on PC2. Our results pointed out a relationship
      between PC1 (PCBs, PBDE, DDE, and DDT compounds) and interfollicular fibrosis in
      the harbour porpoise thyroids. Such an association is not alone sufficient for a
      cause-effect relationship but supports the hypothesis of a contaminant-induced
      thyroid fibrosis in harbour porpoises raising the question of the long-term
      viability in highly polluted areas.

PMID- 16465559
TI  - Exposure to cadmium-phenanthrene mixtures elicits complex toxic responses in the
      freshwater tubificid oligochaete, Ilyodrilus templetoni.
AB  - The joint toxicity of metal-hydrocarbon mixtures in sediments was investigated
      using cadmium (Cd) and phenanthrene (Phen) as model contaminants. Sediment
      bioassays were utilized to quantify effects of individual and combined
      contaminants in the bulk-deposit feeding oligochaete Ilyodrilus templetoni.
      Combined contaminants elicited antagonistic lethal effects and independent
      responses for feeding rate (measured as sediment ingestion). The 10-d LC(50) for
      Cd alone was 1375 mg kg(-1) (95% C.I. 1340-1412), whereas Phen elicited no
      mortality even when loaded to sediment saturation. The presence of Phen decreased
      Cd lethality, increasing the LC(50) of Cd by as much as 40%. Regression analyses
      indicated that Phen was nearly 10 times more potent than Cd in eliciting feeding
      rate reductions. Exposure to Cd-Phen mixtures resulted in feeding rate reductions
      equivalent to those caused by Phen alone. The marked reduction in sediment
      ingestion induced by the co-pollutant Phen reduced exposure to Cd via ingestion.
      We suggest that this Phen-induced reduction in Cd exposure decreased Cd
      bioaccumulation and subsequent lethality. More generally, we suggest that even if
      the toxicological effects among dissimilarly acting chemicals (including metals
      and hydrocarbons) are independent, contaminant mixtures may elicit unexpected
      interactive effects facilitated by modifying exposure.

PMID- 16465560
TI  - The acute and chronic toxicity of hexadecyl and heptadecyl sulfate to aquatic
      organisms.
AB  - HSAS (high-solubility alkyl sulfate) is a new anionic surfactant composed
      predominantly of methyl and ethyl branched hexadecyl and heptadecyl sulfate.
      Effects of HSAS on a wide range of fish, algae, and invertebrates were
      investigated in conventional laboratory toxicity tests as well as in exposures
      conducted as part of an experimental stream model ecosystem study. For
      invertebrates and fish, C(16.7)HSAS (average alkyl chain length 16.7) acute
      LC(50) values ranged from 0.23 (channel catfish) to 2.9 (Asiatic clam, Corbicula)
      mg/L in well and river waters. LC(50) values for those species tested in both
      waters were typically within a factor of 1.5 and all were within a factor of 2 of
      each other, suggesting bioavailability is similar in these waters. Chronic
      toxicity values ranged from 0.070 (fathead minnow) to 0.42 (amphipod, Hyalella)
      mg/L across fish and invertebrates with algal chronic toxicity values ranging
      from 0.5 (blue-green algae, Anabaena flos-aquae) to 7.8 (green algae,
      Scenedesmus) mg/L. The order of sensitivity to HSAS acute and chronic toxicity
      was fish = invertebrate > algae. Based on the chronic single species sensitivity
      distribution, the concentrations protective of 90 and 95% of species were
      estimated to be 0.058 and 0.036 mg/L, respectively. These compare well with the
      model ecosystem NOEC of 0.064 mg/L.

PMID- 16465561
TI  - Indigenous systems of forest classification: understanding land use patterns and
      the role of NTFPs in shifting cultivators' subsistence economies.
AB  - This article discusses the system of classification of forest types used by the
      Pwo Karen in Thung Yai Naresuan Wildlife Sanctuary in western Thailand and the
      role of nontimber forest products (NTFPs), focusing on wild food plants, in Karen
      livelihoods. The article argues that the Pwo Karen have two methods of forest
      classification, closely related to their swidden farming practices. The first is
      used for forest land that has been, or can be, swiddened, and classifies forest
      types according to growth conditions. The second system is used for land that is
      not suitable for cultivation and looks at soil properties and slope. The article
      estimates the relative importance of each forest type in what concerns the
      collection of wild food plants. A total of 134 wild food plant species were
      recorded in December 2004. They account for some 80-90% of the amount of edible
      plants consumed by the Pwo Karen, and have a base value of Baht 11,505 per year,
      comparable to the cash incomes of many households. The article argues that the
      Pwo Karen reliance on NTFPs has influenced their land-use and forest management
      practices. However, by restricting the length of the fallow period, the Thai
      government has caused ecological changes that are challenging the ability of the
      Karen to remain subsistence oriented. By ignoring shifting cultivators'
      dependence on such products, the involvement of governments in forest management,
      especially through restrictions imposed on swidden farming practices, is likely
      to have a considerable impact on the livelihood strategies of these communities.

PMID- 16465562
TI  - An event-based approach for examining the effects of wildland fire decisions on
      communities.
AB  - Public concern over the consequences of forest fire to wildland interface
      communities has led to increased resources devoted to fire suppression, fuel
      treatment, and management of fire events. The social consequences of the
      decisions involved in these and other fire-related actions are largely unknown,
      except in an anecdotal sense, but do occur at a variety of temporal and social
      organizational scales. These consequences are not limited to the fire event
      itself. Preparation for the possibility of a fire, actions that suppression
      agencies take during a fire, and postfire decisions all have consequences, if
      unknown currently. This article presents an "event-based" approach that can be
      useful for constructing and systematic discussion about the consequences of
      wildland fire to human communities. For each of the three major periods within
      this approach, agencies, communities, and individuals make decisions and take
      actions that have consequences. The article presents an integrated, temporally
      based process for examining these consequences, which is similar to others
      developed in the natural hazards and disaster management literature.

PMID- 16465563
TI  - Importance of riparian forests in urban catchments contingent on sediment and
      hydrologic regimes.
AB  - Forested riparian corridors are thought to minimize impacts of landscape
      disturbance on stream ecosystems; yet, the effectiveness of streamside forests in
      mitigating disturbance in urbanizing catchments is unknown. We expected that
      riparian forests would provide minimal benefits for fish assemblages in streams
      that are highly impaired by sediment or hydrologic alteration. We tested this
      hypothesis in 30 small streams along a gradient of urban disturbance (1-65% urban
      land cover). Species expected to be sensitive to disturbance (i.e., fluvial
      specialists and "sensitive" species that respond negatively to urbanization) were
      best predicted by models including percent forest cover in the riparian corridor
      and a principal components axis describing sediment disturbance. Only sites with
      coarse bed sediment and low bed mobility (vs. sites with high amounts of fine
      sediment) had increased richness and abundances of sensitive species with higher
      percent riparian forests, supporting our hypothesis that response to riparian
      forests is contingent on the sediment regime. Abundances of Etheostoma scotti,
      the federally threatened Cherokee darter, were best predicted by models with
      single variables representing stormflow (r(2) = 0.34) and sediment (r(2) = 0.23)
      conditions. Lentic-tolerant species richness and abundance responded only to a
      variable representing prolonged duration of low-flow conditions. For these
      species, hydrologic alteration overwhelmed any influence of riparian forests on
      stream biota. These results suggest that, at a minimum, catchment management
      strategies must simultaneously address hydrologic, sediment, and riparian
      disturbance in order to protect all aspects of fish assemblage integrity.

PMID- 16465564
TI  - Comparing onsite and offsite methods for measuring norms for trail impacts.
AB  - This study examined the comparability of onsite and offsite methods for measuring
      norms for trail impacts using photo/survey techniques. A total of 449 subjects
      participated in a study of Mudeung-Mountain Provincial Park, Gwang-Ju, Korea. For
      the overall photo evaluation method (OPEM), respondents rated the acceptability
      of bare soil area for each of a series of photographs. For the specific photo
      evaluation method (SPEM), respondents selected a photograph that illustrated the
      largest acceptable proportion of bare soil area from a series of 10 photographs.
      Overall, there were no substantial differences in maximum acceptable impacts
      between onsite (onsite-I visitor group surveyed at the actual trail points and
      onsite-II departing visitor group surveyed at the exit area) and offsite
      (students surveyed in a laboratory setting) groups for the two norm measurement
      alternatives (OPEM and SPEM). Subjects' difficulty ratings were low for both
      methods, and there were no substantial differences in norms between individuals
      with high and low levels of experience at the park. The offsite method appears to
      be substitutable for onsite methods in this particular study area, which is a
      frontcountry setting with a relatively simple range of recreation opportunities.
      Implications and further studies are discussed.

PMID- 16465565
TI  - Pitfalls of applying adaptive management to a wolf population in Algonquin
      Provincial Park, Ontario.
AB  - We examined adaptive management (AM), applied as a science with testable and
      falsifiable hypothesis, in the context of a large carnivore population,
      specifically to wolf (Canis lupus lycaon) management in Algonquin Provincial
      Park, Ontario, Canada. Evidence of a population decline was based upon 12 years
      of data on 137 different radio-collared wolves. Because human killing accounted
      for an average of 66% of deaths, and most killing occurred adjacent to the park,
      a management prescription of complete protection for wolves around the park for
      30 months was initiated in January 2001. We evaluated the probability of being
      able to test the null hypothesis, that protecting wolves adjacent to the park for
      30 months would not result in a positive population response. Using preceding
      variances in population change, yearling recruitment, and mortality rates, we
      conducted this evaluation in two ways, the former involving a power analysis, the
      latter involving modeling. Both approaches showed the falsifiability of the
      hypothesis to be low. The reason, inherent in the application of AM to issues of
      population biology, especially of large carnivores, was stochasticity of the
      ecological system and time constraints of the human system. We discuss the
      political background that led up to the management prescription, and ways to
      avoid misapplication of a scientific approach to AM in such situations. For the
      latter, the merit of adjusting the relative probability levels of making Type I
      or Type II errors are discussed, along with recommendations that in the interests
      of conservation, avoiding a Type II error holds precedence.

PMID- 16465566
TI  - Optimal environmental management strategy and implementation for groundwater
      contamination prevention and restoration.
AB  - An innovative management strategy is proposed for optimized and integrated
      environmental management for regional or national groundwater contamination
      prevention and restoration allied with consideration of sustainable development.
      This management strategy accounts for availability of limited resources, human
      health and ecological risks from groundwater contamination, costs for groundwater
      protection measures, beneficial uses and values from groundwater protection, and
      sustainable development. Six different categories of costs are identified with
      regard to groundwater prevention and restoration. In addition, different
      environmental impacts from groundwater contamination including human health and
      ecological risks are individually taken into account. System optimization
      principles are implemented to accomplish decision-makings on the optimal
      resources allocations of the available resources or budgets to different existing
      contaminated sites and projected contamination sites for a maximal risk
      reduction. Established management constraints such as budget limitations under
      different categories of costs are satisfied at the optimal solution. A stepwise
      optimization process is proposed in which the first step is to select optimally a
      limited number of sites where remediation or prevention measures will be taken,
      from all the existing contaminated and projected contamination sites, based on a
      total regionally or nationally available budget in a certain time frame such as
      10 years. Then, several optimization steps determined year-by-year optimal
      distributions of the available yearly budgets for those selected sites. A
      hypothetical case study is presented to demonstrate a practical implementation of
      the management strategy. Several issues pertaining to groundwater contamination
      exposure and risk assessments and remediation cost evaluations are briefly
      discussed for adequately understanding implementations of the management
      strategy.

PMID- 16465567
TI  - Percutaneous insertion of Zilver stent in malignant biliary obstruction.
AB  - BACKGROUND: We evaluated the clinical efficacy and technical feasibility of the
      percutaneously inserted self-expandable nitinol stent (Zilver stent) for
      palliation of malignant biliary obstruction. METHODS: Seventeen patients with
      malignant tumors involving the intra- or extrahepatic bile duct who presented
      with obstructive jaundice underwent percutaneous insertion of a self-expandable
      nitinol stent. We retrospectively reviewed the hospital records of patients and
      evaluated the technical feasibility on stent placement, complications, patient
      survival, and duration of stent patency. RESULTS: Percutaneous biliary stenting
      with 27 Zilver stents was performed in 17 patients with malignant biliary
      obstruction. Technical success was 95%. Malposition of the stent was encountered
      in one patient. Minor technical problems were encountered in two patients: the
      introducer tip was broken during stent insertion, so endoscopic removal was done.
      Mean follow-up period for the 17 patients was 182 days (range 29-485 days): nine
      patients died of progressive disease at a mean follow-up of 151 days (range 61
      371days) after stent insertion and eight patients remained alive at the final
      follow-up of 216 days (range 29-485 days). The median survival period for all
      patients was 277 days. The stent occlusion rate was 26% and the mean patency
      period was 280 days. In five patients, seven stents were obstructed by tumor
      ingrowth and overgrowth. Stent patency rates were 100%, 100%, 75%, 61%, and 41%
      at 1, 2, 3, 6, and 12 months, respectively. A late complication, erosive bleeding
      of the hepatic artery by the stent, developed in one patient. CONCLUSION:
      Percutaneous biliary stenting using the nitinol stent is technically feasible and
      safe and clinically efficacious treatment for malignant biliary obstruction, even
      with a minor technical problem during stent insertion.

PMID- 16465568
TI  - Hepatic portal venous gas in a patient with enterovascular fistula.
AB  - Hepatic portal venous gas is an uncommon clinical condition that is often
      characterized by acute onset of abdominal pain and is associated with a high rate
      of mortality despite clinical and/or surgical treatment. Radiologic diagnosis is
      important and usually includes abdominal radiography, ultrasound, and computed
      tomography. We describe the clinical, computed tomographic, and angiographic data
      of a patient with sigmoid diverticulitis who developed a massive embolism of the
      intra- and extrahepatic portal systems due to an enterovascular fistula and was
      treated with fistula embolization and subsequent sigmoidectomy.

PMID- 16465569
TI  - Pancreatic pseudotumor in Meckel diverticulum.
AB  - This report describes the ultrasonic appearance of an ectopic pancreatic rest
      presenting as a mass within an intussusception due to an inverted Meckel
      diverticulum. Familiarity with the ultrasound appearance of this entity may be
      useful to obviate unnecessary imaging workup.

PMID- 16465571
TI  - Magnetic resonance (MR) imaging and MR angiography for evaluation and follow-up
      of hepatic artery banding in patients with hepatic involvement of hereditary
      hemorrhagic telangiectasia.
AB  - BACKGROUND: We describe findings obtained by magnetic resonance angiography (MRA)
      and magnetic resonance imaging (MRI) for evaluation and follow-up after hepatic
      artery banding in patients with hepatic involvement of hereditary hemorrhagic
      telangiectasia (HHT). METHODS: Abdominal MRA and liver MRI were performed in
      three patients with HHT as clinically defined by Curacao criteria. One patient
      underwent MRA and MRI twice for preinterventional evaluation and follow-up, one
      patient for preinterventional evaluation, and one patient for postinterventional
      evaluation. Hepatic vascular involvement of the disease and postinterventional
      vascular anatomy were evaluated by two radiologists by consensus. RESULTS:
      Hepatic vascular involvement with perfusion disorders and arteriosystemic shunts
      was found in all three patients. MRA and MRI allowed diagnostic characterization
      of hepatic vascular disease (three of three), preinterventional evaluation of
      complex vascular anatomy and variants (two of two), and postinterventional follow
      up of hepatic artery banding (two of two). CONCLUSION: In preinterventional
      evaluation and postinterventional follow-up, MRA and MRI allows characterization
      of complex hepatic vascular alterations of HHT and, hence, is an alternative to
      other imaging modalities in the diagnosis, clinical decision making, and follow
      up of HHT.

PMID- 16465570
TI  - Unusual perforated appendicitis within umbilical hernia: CT findings.
AB  - We present the first imaging report of perforated appendicitis in an umbilical
      hernia. Computed tomography demonstrated a gas-forming abscess within an
      umbilical hernia and the cecum was found inside the hernial sac, with an inner
      relation to the abscess. Computed tomographic findings suggested appendicitis as
      possible diagnosis, which was confirmed at surgery. Physicians must consider
      appendicitis within the differential diagnosis of an abdominal abscess located
      near to the cecum, even at an unexpected location.

PMID- 16465572
TI  - Portal systemic shunt through the renal vein.
AB  - BACKGROUND: Despite the semi-routine use of color Doppler sonography for
      evaluating portal circulation abnormalities, there is a relative paucity of
      detailed color Doppler findings of portal systemic (P-S) shunt through the renal
      vein (P-SR shunt). METHODS: We reviewed the color Doppler findings of 18 patients
      with P-SR shunt to determine its clinical significance and appropriate scanning
      techniques for diagnosing accurately P-SR shunt. RESULTS: The splenorenal shunt
      was imaged as a highly tortuous vessel at the splenic hilum, which then coursed
      backward behind the spleen. Splenic vein flow was reversed or very slow. The
      gastrorenal shunt originated from the splenic vein, coursed backward, and joined
      the left renal vein. Flow direction in the splenic vein was always hepatopetal.
      The P-S shunt through the right renal vein originated from duodenal or jejunal
      varices, coursed posterolaterally, and joined the right renal vein at the renal
      hilum. CONCLUSION: Familiarity with these color Doppler findings will help
      increase the diagnostic confidence of P-SR shunt by color Doppler sonography.

PMID- 16465573
TI  - Dynamic MR urography in urinary tract obstruction: implementation and preliminary
      results.
AB  - BACKGROUND: Recent studies have demonstrated magnetic resonance (MR) capabilities
      in evaluating renal morphology and function in patients with urinary obstruction.
      The objective of this report is to support the introduction of dynamic MR
      renography on any MR equipment. METHODS: A custom-made device of vials filled
      with different concentrations of gadolinium was studied by combinations of T1
      weighted gradient-echo sequences and coils. We compared the capabilities of two
      coils (phased array vs. standard body), the properties of dynamic sequences, and
      the effects of increasing concentrations of gadolinium on signal intensity. In a
      second section, we designed MR urography plug-ins of Image J (DICOM image
      software) for the analysis of dynamic studies. RESULTS: Optimized gradient-echo
      sequences acquired with a phased array body coil produced acceptable quality
      images with a linear relation between signal intensity and the lowest
      concentrations of gadolinium. In vitro measurements showed loss of linearity
      above 8 mmol/L. CONCLUSION: Theoretical calculation and data from the literature
      suggest that the gadolinium dose to the patient should not exceed one-fourth of
      the usual one (0.025 mmol/kg). Postprocessing using Image J software and the
      specifically designed plug-ins was validated. The collection of plug-ins is now
      available on the Internet.

PMID- 16465574
TI  - Using the ovarian vein to find the ovary.
AB  - Computed tomograms of 68 adult women who had undergone contrast-enhanced, 5-mm
      helical computed tomography of the abdomen and pelvis were retrospectively
      reviewed to determine whether the ovarian vein could be used to locate the ovary.
      Subjects were 17 to 84 years of age (mean 45 years); 31 scans were normal, and 37
      showed pelvic masses. Both ovarian veins were identified at their termination and
      were followed into the pelvis by scrolling through the set of venous phase images
      with a manual cine-paging tool. All 68 left ovarian veins and 67 of 68 right
      ovarian veins were identified. All visualized ovarian veins led to a normal ovary
      or to an ovarian mass. There were no anatomic variations. In 13 ovaries displaced
      by pathology in the pelvis, the ovarian vein was correspondingly displaced and
      indicated the altered ovarian position. In all 14 patients with non-ovarian
      pelvic masses, ovarian veins led to the normal ovary; the vein and ovary were
      markedly displaced in three of these patients. On computed tomography, the
      ovarian vein can be consistently identified. By tracing the vein into the pelvis,
      the ovarian or non-ovarian nature of a pelvic mass can be determined.

PMID- 16465576
TI  - Omental infarct: CT imaging features.
AB  - BACKGROUND: The aim of this study is to describe contrast-enhanced computed
      tomographic (CT) features of acute omental infarction and to study the
      evolutionary changes on follow-up CT imaging. METHODS: Fifteen cases of omental
      infarction were evaluated for their initial CT imaging features. The imaging
      features evaluated included size of the fatty lesion, location, peripheral rim,
      and relation to colon. CT findings were correlated with etiology, clinical
      presentation, and leukocytosis. Follow-up CT images were available in eight
      patients and the imaging features were studied. RESULTS: Eight omental infarcts
      were of unknown etiology and seven were secondary to abdominal surgery. In 53% of
      patients (eight of 15), the location of the omental infarct was in the right
      lower, mid, or upper quadrants. These eight right-side infarcts occurred in six
      patients with primary omental infarcts. In 13 of 14 patients who underwent CT
      within 15 days of onset of omental infarct, the margin of the lesion was ill
      defined. Primary omental (n = 8) infarcts were seen in younger patients (p =
      0.02) and were larger on CT (p = 0.02) compared with secondary omental infarcts.
      CT findings evolved from an ill-defined, heterogeneous fat-density lesion to a
      well-defined, heterogeneous fat-density lesion with a peripheral hyperdense rim
      in all six secondary omental infarctions for which acute stage and follow-up CT
      images were available for interpretation. CONCLUSION: There is a significant
      difference in the age distribution and CT findings in terms of size of the
      omental infarction between primary and secondary etiologies. On follow-up CT,
      secondary omental infarcts progressively shrank and developed a well-defined,
      hyperdense rim around a fatty core.

PMID- 16465577
TI  - Staging of gastric cancer with 16-channel MDCT.
AB  - Early detection and accurate preoperative staging of gastric cancer are
      clinically important because the prognosis and choice of an optimal therapeutic
      approach are directly related to the stage of a neoplasm at time of presentation.
      Multidetector row computed tomography is a potentially powerful tool for
      noninvasive gastric evaluation. When thin collimation is used, near-isotropic
      imaging of the stomach is possible. Proper air distention of the stomach is used
      with virtual gastroscopic images; the technique is able to evaluate endoluminal
      lesions of the stomach and assist in early detection of gastric cancer. Adequate
      water-filled dynamic multiplanar reformatted images allow the radiologist to
      choose the optimal imaging plane to accurately evaluate depth of tumor invasion
      of the gastric wall and perigastric fat plane infiltration, identify a thin fat
      plane between a tumor and adjacent organs, avoid partial volume averaging
      effects, and better differentiate lymph nodes from small perigaskric vessels.
      Thus, the combination of air distention and hydrodistention of the stomach and
      dynamic contrast-enhanced multidetector row computed tomography with near
      isotropic imaging offer improved diagnosis and staging of gastric cancers.

PMID- 16465578
TI  - Staging of pancreatic cancer with multidetector CT in the setting of preoperative
      chemoradiation therapy.
AB  - BACKGROUND: Preoperative chemoradiation can potentially improve outcomes in
      patients with pancreatic cancer. This study addresses its effect on staging
      pancreatic cancer with multidetector computed tomography (MDCT). METHODS: Fifty
      five patients underwent a dual-phase MDCT pancreas protocol for proved pancreatic
      cancer. Of these, 16 patients underwent preoperative chemoradiation. Three
      radiologists independently reviewed images to assess for locally advanced
      disease, liver and peritoneal metastases on baseline studies of all 55 patients,
      and on follow-up preoperative studies for the 16 patients receiving preoperative
      therapy. Overall score for resectability was graded on a scale from 1 to 5 (1,
      definitely resectable; 5. definitely unresectable). Receiver operating
      characteristic curves and weighted (kappa statistics were determined. RESULTS:
      The areas under the receiver operating characteristic curves for readers 1, 2,
      and 3 were 0.98, 0.96, and 0.90, respectively. Weighted kappa values for reader 1
      versus reader 2, reader 1 versus reader 3, and reader 2 versus reader 3 were
      0.90, 0.57, and 0.54, respectively. Interpreting scores of 1 to 3 for
      resectability as resectable disease, the mean values for sensitivity,
      specificity, negative predictive value, positive predictive value, and accuracy
      were 0.92, 0.91, 0.74, 0.98, and 0.92 respectively. CONCLUSION: The negative
      predictive value for MDCT for identifying unresectable pancreatic cancer in the
      setting of preoperative therapy is comparable to that reported in the absence of
      neoadjuvant therapy.

PMID- 16465579
TI  - Early gastric cancer: virtual gastroscopy.
AB  - Gastric cancer is one of the most common cancers and one of the most frequent
      causes of cancer-related deaths worldwide. Early detection and accurate
      preoperative staging of early gastric cancer (ECG) offers the best prognosis and
      is essential for planning optimal therapy such as endoscopic mucosal resection or
      gastric resection. Recent advances in computed tomographic technology and three
      dimensional imaging software have enabled more accurate gastric imaging. Virtual
      gastroscopy (VG) is helpful in the detection and evaluation of EGC in the same
      way as gastroscopy. VG has a wider field of view than conventional gastroscopy,
      the angle of the virtual cancer can be adjusted omnidirectionally, and it has no
      blind point because retrospective reconstruction is available. Thus, VG is a
      promising method for evaluating gastric lesions despite its limitations. This
      report describes the clinical usefulness of VG with multidetector row computed
      tomography for EGC and axial computed tomography.

PMID- 16465580
TI  - Fentanyl-augmented MRCP.
AB  - BACKGROUND: Drugs such as secretin and morphine have been used to augment the
      visualization of magnetic resonance cholangiopancreatography (MRCP). This study
      investigated the effectiveness of intravenous administration of a synthetic
      opioid, fentanyl, in improving the MRCP image quality. METHODS: Thirty
      consecutive patients with a provisional diagnosis of benign biliary and/or
      pancreatic disease underwent MRCP. Coronal single-shot fast spin-echo heavily T2
      weighted dynamic MRCP images were generated before and at every minute for 10 min
      after intravenous administration of fentanyl citrate at a dose of 1.0 mug/kg. Pre
      and postinjection images were compared and analyzed qualitatively and
      quantitatively. RESULTS: Qualitatively, visualization of intrahepatic bile ducts,
      common bile duct, and main pancreatic duct improved after fentanyl injection in
      five (16%), 11 (37%), and 19 (63%) patients, respectively. The pancreatobiliary
      junction and common channel were visualized better after fentanyl injection in
      eight of the 18 patients (44%). Quantitatively, signal intensity and diameters of
      the intrahepatic ducts, common bile duct, and main pancreatic duct measured at
      corresponding points on pre- and postinjection images showed an increase above
      preinjection values in 28 (93%), 27 (90%), and 21 (70%) and in 18 (60%), 26
      (86%), and 22 (73%), respectively, and these changes were highly significant at
      all sites (p < 0.001). CONCLUSIONS: Intravenous administration of fentanyl before
      MRCP improves qualitative and quantitative visualization of the ductal system
      anatomy that may be of value in clinical diagnosis and management.

PMID- 16465582
TI  - Secretin-stimulated MRCP.
AB  - Secretin-stimulated magnetic resonance cholangiopancreatography not only
      facilitate the depiction of anatomic variations or morphologic changes of the
      pancreatic duct in the normal and diseased pancreas but also help assessing
      functional abnormalities of the exocrine pancreas. In this article, we illustrate
      findings of normal pancreas and various pancreatic diseases on magnetic resonance
      cholangiopancreatography after secretin stimulation.

PMID- 16465583
TI  - Imaging diagnosis of testicular lymphoma.
AB  - Testicular lymphoma is a rare clinicopathologic entity that has rapid progression
      and poor prognosis. This report describes a case of a 62-year-old man who
      presented with a large testicular tumor and extensive lymphadenopathy along the
      spermatic cord and gonadal vessels to the renal vein level. Testicular lymphoma
      was considered, and biopsy confirmed a non-Hodgkin, large, B-cell lymphoma. The
      distribution of lymphadenopathy differs from that of paraaortic lymph nodes that
      present as other testicular tumors (seminoma or nonseminoma). The finding may be
      a useful characteristic for timely diagnosis of testicular lymphoma, although the
      diagnosis should be suspected in an older patient who presents with a testicular
      neoplasm and increased lactic dehydrogenase levels but without increased alpha
      fetoprotein and human chorionic gonadotropin levels.

PMID- 16465584
TI  - Gastrointestinal stromal tumors.
AB  - BACKGROUND: We reviewed radiologic features of gastrointestinal stromal tumors
      (GISTs) and correlated them with clinical and pathologic findings. METHODS: We
      investigated a series of 39 c-Kit-positive GISTs. Clinical and radiologic
      findings and management of these patients were recorded. RESULTS: Twenty women
      and 19 men (mean age 64 years) had histologically proved GIST. Tumor locations
      were the small bowel (n = 20), stomach (n = 14), rectum (n = 4), and omentum (n =
      l). Symptoms at presentation were most frequently gastrointestinal bleeding (n =
      14) and abdominal pain (n = l1). Tumors were classified as very low risk (n = 2),
      low risk (n = 10), intermediate risk (n = 12), and high risk (n = 11).
      Ultrasonography, computed tomography, magnetic resonance, digital subtraction
      angiography, and barium series were used in the evaluation of these tumors. Most
      tumors were seen as well-delineated soft tissue masses with heterogeneous
      contrast enhancement. Necrosis, calcification, and ulceration were most commonly
      seen in large tumors that presented a more aggressive behavior. CONCLUSION: GISTs
      can arise anywhere in the gastrointestinal tract and present a great variety of
      clinical and radiologic features, depending mostly on size and location.

PMID- 16465585
TI  - Management of recurrent rectal prolapse: surgical approach influences outcome.
AB  - INTRODUCTION: Recurrent rectal prolapse is an unresolved problem and the optimal
      treatment is debated. This study was designed to review patterns of care and
      outcomes in a large cohort of patients after surgery for recurrent prolapse.
      METHODS: From 685 patients who underwent operative repair for full-thickness
      external rectal prolapse, we identified 78 patients (70 females; mean age, 66.9
      years) who underwent surgery for recurrence. We reviewed the subsequent
      management and outcomes for these 78 patients. RESULTS: Mean interval to their
      first recurrence was 33 (range, 1-168) months. There were significantly more re
      recurrences after reoperation using a perineal procedure (19/51) compared with an
      abdominal procedure (4/27) for their recurrent rectal prolapse (P = 0.03) at a
      mean follow-up of nine (range, 1-82) months. Patients undergoing abdominal repair
      of recurrence were significantly younger than those who underwent perineal repair
      (mean age, 58.5 vs. 71.5 years; P < 0.01); however, there was nosignificant
      difference between the two groups with regard to the American Society of
      Anesthesiologists classification (P = 0.89). Eighteen patients had surgery for a
      second recurrence, with perineal repairs associated with higher failure rates (50
      vs. 8 percent; P = 0.07). Finally, when combining all repairs, the abdominal
      approach continued to have significantly lower recurrence rates (39 vs. 13
      percent; P < 0.01). CONCLUSIONS: The re-recurrence rate after surgery for
      recurrent rectal prolapse is high, even at a relatively short follow-up interval.
      Our data suggest that abdominal repair of recurrent rectal prolapse should be
      undertaken if the patient's risk profile permits this approach.

PMID- 16465586
TI  - Massive hematochezia from acute hemorrhagic rectal ulcer in patients with severe
      comorbid illness: rapid control of bleeding by per anal suturing of bleeder using
      anoretractor.
AB  - PURPOSE: Massive hematochezia from acute hemorrhagic rectal ulcer can arise in
      patients with severe comorbid illness who are bedridden for long periods. If the
      bleeder is not found and treated immediately, the bleeding will cause
      deterioration of health and even threaten life. The results of the current study
      show how quickly and safely per anal suturing can treat acute hemorrhagic rectal
      ulcer. METHODS: From January 2003 to December 2003, the records of 26 patients
      who underwent per anal suturing of acute hemorrhagic rectal ulcer were
      retrospectively reviewed. The identification of acute hemorrhagic rectal ulcer
      was confirmed by clinical and anoscopic examination. RESULTS: Most of these
      patients were elderly and bedridden (14 men; median age 69 years). Main comorbid
      illnesses existed in all patients and included liver cirrhosis (8 patients, 31
      percent), sepsis (13 patients, 50 percent), cerebral vascular accident (15
      patients, 58 percent), respiratory failure (13 patients, 50 percent), and
      malignancy (7 patients, 27 percent). Effective hemostasis was achieved in all
      patients by direct suture of bleeding ulcer. No complications developed relative
      to the per anal suturing procedure among any patients. Although 11 patients
      developed recurrent hematochezia, 9 patients responded to repeated therapy. The
      risk factors associated with recurrent bleeding were severity of disease and
      abnormal coagulation. CONCLUSIONS: When massive hematochezia occurs in bedridden
      patients with severe comorbid illness, it is essential to investigate the lower
      rectum, which often is affected by acute hemorrhagic rectal ulcer. Recognition of
      this clinical presentation will result in early identification and therapy. Per
      anal suturing of a bleeder at the bedside provides a quick, safe, and successful
      management of acute hemorrhagic rectal ulcer.

PMID- 16465589
TI  - Genotype-specific environmental impact on the variance of blood values in inbred
      and F1 hybrid mice.
AB  - Mice are important models for biomedical research because of the possibility of
      standardizing genetic background and environmental conditions, which both affect
      phenotypic variability. Inbred mouse strains as well as F1 hybrid mice are
      routinely used as genetically defined animal models; however, only a few studies
      investigated the variance of phenotypic parameters in inbred versus F1 hybrid
      mice and the potential interference of the genetic background with different
      housing conditions. Thus, we analyzed the ranges of clinical chemical and
      hematologic parameters in C3H and C57BL/6 inbred mice and their reciprocal F1
      hybrids (B6C3F1, C3B6F1) in two different mouse facilities. Two thirds of the
      blood parameters examined in the same strain differed between the facilities for
      both the inbred strains and the F1 hybrid lines. The relation of the values
      between inbred and F1 hybrid mice was also affected by the facility. The variance
      of blood parameters in F1 hybrid mice compared with their parental inbred strains
      was inconsistent in one facility but generally smaller in the other facility. A
      subsequent study of F1 hybrid animals derived from the parental strains C3H and
      BALB/c, which was done in the latter housing unit, detected no general difference
      in the variance of blood parameters between F1 hybrid and inbred mice. Our study
      clearly demonstrates the possibility of major interactions between genotype and
      environment regarding the variance of clinical chemical and hematologic
      parameters.

PMID- 16465590
TI  - The Purkinje cell degeneration 5J mutation is a single amino acid insertion that
      destabilizes Nna1 protein.
AB  - In the mouse, Purkinje cell degeneration (pcd) is a recessive mutation
      characterized by degeneration of cerebellar Purkinje cells, retinal
      photoreceptors, olfactory bulb mitral neurons, and certain thalamic neurons, and
      is accompanied by defective spermatogenesis. Previous studies of pcd have led to
      the identification of Nna1 as the causal gene; however, how loss of Nna1 function
      results in neurodegeneration remains unresolved. One useful approach for
      establishing which functional domains of a protein underlie a recessive phenotype
      has been to determine the genetic basis of the various alleles at the locus of
      interest. Because none of the pcd alleles analyzed at the time of the
      identification of Nna1 provided insight into the molecular basis of Nna1 loss-of
      function, we obtained a recent pcd remutation--pcd5J, and after determining that
      its phenotype is comparable to existing pcd severe alleles, we sought its genetic
      basis by sequencing Nna1. In this article we report that pcd5J results from the
      insertion of a single GAC triplet encoding an aspartic acid residue at position
      775 of Nna1. Although this insertion does not affect Nna1 expression at the RNA
      level, Nna1pcd-5J protein expression is markedly decreased. Pulse-chase
      experiments reveal that the aspartic acid insertion dramatically destabilizes
      Nna1pcd-5J protein, accounting for the observation that pcd5J is a severe allele.
      The presence of a readily detectable genetic mutation in pcd5J confirms that Nna1
      loss-of-function alone underlies the broad pcd phenotype and will facilitate
      further studies of how Nna1 loss-of-function produces neurodegeneration and
      defective spermatogenesis in pcd mice.

PMID- 16465591
TI  - Two new behavioral QTLs, Emo4 and Reb1, map to mouse Chromosome 1: Congenic
      strains and candidate gene identification studies.
AB  - By use of newly developed subcongenic strains of mice from a parental B6.129-Il10
      /- knockout/congenic strain, we have narrowed the critical region for a new
      behavioral QTL, called Emo4, for open-field activity to a segment of Chromosome 1
      between Erbb4 (68.4Mb) and B3gnt7 (86.2 Mb). We have also uncovered an additional
      QTL governing repetitive beam breaks in the open field. This QTL, called Reb1,
      maps to the interval between Asb1 (91.4 Mb) and NM_172851 (100.0 Mb) and is one
      of the first QTLs mapped for this type of behavior. Genome-wide microarray
      expression analyses were then undertaken to help to identify candidate genes that
      may be the cause of these genetic differences in open-field performance. In this
      effort, we analyzed global gene expression differences in the amygdalae by use of
      Affymetrix GeneChips between B6, B6.129-Il10-/-, and B6.129R4. Several probe sets
      representing target Chr 1 genes were found that showed significantly differential
      expression in the subcongenic and congenic strains. Several candidate genes have
      been identified. One of these regions coincides with an homologous region in
      humans that has been associated with autism, a disease whose symptoms include
      repetitive actions. This study illustrates that the use of congenic strains
      combined with global gene expression analyses can produce a list of viable
      candidates. It further shows that caution should be observed when analyzing the
      effects of knockout/congenic strains because many of the gene expression
      differences in these comparisons could not be attributable to the ablated Il10
      gene but rather to passenger gene effects.

PMID- 16465592
TI  - Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous
      malformations.
AB  - Cerebral cavernous malformations are vascular defects of the central nervous
      system consisting of clusters of dilated vessels that are subject to frequent
      hemorrhaging. The genes mutated in three forms of autosomal dominant cerebral
      cavernous malformations have been cloned, but it remains unclear which cell type
      is ultimately responsible for the lesion. In this article we describe mice with a
      gene trap insertion in the Ccm2 gene. Consistent with the human phenotype,
      heterozygous animals develop cerebral vascular malformations, although penetrance
      is low. Beta-galactosidase activity in heterozygous brain and in situ
      hybridization in wild-type brain revealed Ccm2 expression in neurons and choroid
      plexus but not in vascular endothelium of small vessels in the brain. The
      expression pattern of Ccm2 is similar to that of the Ccm1 gene and its
      interacting protein ICAP1 (Itgb1bp1). These data suggest that cerebral cavernous
      malformations arise as a result of defects in the neural parenchyma surrounding
      the vascular endothelial cells in the brain.

PMID- 16465593
TI  - A protocol for high-throughput phenotyping, suitable for quantitative trait
      analysis in mice.
AB  - Whole-genome genetic association studies in outbred mouse populations represent a
      novel approach to identifying the molecular basis of naturally occurring genetic
      variants, the major source of quantitative variation between inbred strains of
      mice. Measuring multiple phenotypes in parallel on each mouse would make the
      approach cost effective, but protocols for phenotyping on a large enough scale
      have not been developed. In this article we describe the development and
      deployment of a protocol to collect measures on three models of human disease
      (anxiety, type II diabetes, and asthma) as well as measures of mouse blood
      biochemistry, immunology, and hematology. We report that the protocol delivers
      highly significant differences among the eight inbred strains (A/J, AKR/J,
      BALBc/J, CBA/J, C3H/HeJ, C57BL/6 J, DBA/2 J, and LP/J), the progenitors of a
      genetically heterogeneous stock (HS) of mice. We report the successful collection
      of multiple phenotypes from 2000 outbred HS animals. The phenotypes measured in
      the protocol form the basis of a large-scale investigation into the genetic basis
      of complex traits in mice designed to examine interactions between genes and
      between genes and environment, as well as the main effects of genetic variants on
      phenotypes.

PMID- 16465594
TI  - Expression profiling identifies novel candidate genes for ethanol sensitivity
      QTLs.
AB  - The Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) mouse strains have a 16
      fold difference in duration of loss of the righting response (LORR) following
      administration of a sedative dose of ethanol. Four quantitative trait loci (QTLs)
      have been mapped in these strains for this trait. Underlying each of these QTLs
      must be one or more genetic differences (polymorphisms in either gene coding or
      regulatory regions) influencing ethanol sensitivity. Because prior studies have
      tended to focus on differences in coding regions, genome-wide expression
      profiling in cerebellum was used here to identify candidate genes for regulatory
      region differences in these two strains. Fifteen differentially expressed genes
      were found that map to the QTL regions and polymorphisms were identified in the
      promoter regions of four of these genes by direct sequencing of ILS and ISS
      genomic DNA. Polymorphisms in the promoters of three of these genes, Slc22a4,
      Rassf2, and Tax1bp3, disrupt putative transcription factor binding sites. Slc22a4
      and another candidate, Xrcc5, have human orthologs that map to genomic regions
      associated with human ethanol sensitivity in genetic linkage studies. These genes
      represent novel candidates for the LORR phenotype and provide new targets for
      future studies into the neuronal processes underlying ethanol sensitivity.

PMID- 16465595
TI  - Comparative phylogenetic analysis reveals multiple non-imprinted isoforms of
      opossum Dlk1.
AB  - Imprinted genes are monoallelically expressed in a parent-of-origin manner and
      were previously identified in both marsupials and eutherians, but not in
      monotremes. Phylogenetic comparison of imprinted domains is a powerful tool for
      investigating the molecular and adaptive evolution of this unique gene regulatory
      mechanism. Herein, we report that multiple transcripts of Dlk1 (Delta,
      Drosophila, Homolog-like 1) are expressed in the opossum, but none are imprinted.
      Thus, we provide the first example of a reciprocally imprinted gene domain in
      which imprinting evolved in a common ancestor to eutherian rather than therian
      mammals. Moreover, the reciprocally imprinted Meg3 (Maternally Expressed Gene 3),
      found downstream of Dlk1 in eutherian mammals, is absent in the opossum. We
      propose that the Meg3 sequence integrated into the eutherian Dlk1 domain via a
      LINE-1 element and that Dlk1 became imprinted in eutherian mammals only after
      this downstream integration. These findings clearly demonstrate that imprinted
      genes did not all evolve before the divergence of marsupials and eutherians.

PMID- 16465596
TI  - Reduced TCOF1 mRNA level in a rhesus macaque with Treacher Collins-like syndrome:
      further evidence for haploinsufficiency of treacle as the cause of disease.
AB  - Mutations in the human gene TCOF1 cause a mandibulofacial dysostosis known as
      Treacher Collins syndrome (TCS). An infant rhesus macaque (Macaca mulatta) that
      displayed the TCS phenotype was identified at the California National Primate
      Research Center. The TCOF1 coding region was cloned from a normal rhesus macaque
      and sequenced. The rhesus macaque homolog of TCOF1 is 91.6% identical in cDNA
      sequence and 93.8% identical in translated protein sequence compared to human
      TCOF1. Sequencing of TCOF1 in the TCS-affected rhesus macaque showed no mutations
      within the coding region or splice sites; however, real-time quantitative PCR
      showed an 87% reduction of spleen TCOF1 mRNA level in the TCS affected macaque
      when compared with normal macaque spleen.

PMID- 16465597
TI  - Identification of a tandem duplicated array in the Rhox alpha locus on mouse
      chromosome X.
AB  - The Rhox family of homeobox-containing genes maps to three gene dense clusters,
      alpha, beta, and gamma, on the mouse X chromosome. Rhox genes are expressed
      primarily in reproductive and extra-embryonic tissues and may be regulated by
      colinear mechanisms. Uniquely among family members, Rhox4 is also expressed in
      the developing and adult thymus, where its striking restriction to the third
      pharyngeal pouch has suggested a role in lineage specification. In this article
      we describe a previously unreported duplication within the Rhox alpha locus that
      contains seven copies of Rhox4 and eight copies of Rhox2 and Rhox3 in a tandem
      array. We further show that all seven Rhox4 copies are expressed, although
      preferential expression occurs and differs between tissues. In contrast to
      reproductive tissues, we found no evidence of colinear expression of the Rhox
      alpha cluster during thymus development. All subspecies of mice examined
      contained multiple copies of Rhox4. However, the only predicted ortholog of
      Rhox4, rat Rhox4, is present in a single copy, suggesting that the duplications
      arose at the time of rat and mouse lineage divergence. Finally, no changes in
      Rhox4 expression were detected in mice with defects in thymus organogenesis,
      placing it upstream or outside of established transcriptional pathways.

PMID- 16465598
TI  - Basis of rise in intracellular sodium in airway hyperresponsiveness and asthma.
AB  - The aim of this study was to investigate the basis of disturbances in sodium
      transport in asthma and in airway hyperresponsiveness without symptoms of asthma
      (asymptomatic AHR). We measured the intracellular sodium (Na(i)); activity of
      Na(+)/K(+)-ATPase in unstimulated cells (resting activity) and in cell homogenate
      under optimal conditions (maximal activity); and sodium influx, in mixed
      leukocytes of 15 normal subjects, 12 subjects with asymptomatic AHR, and 26
      asthmatics with or without active symptoms. Resting Na(+)/K(+)-ATPase activity
      was the same as sodium influx, consistent with homeostasis. Compared with normal
      subjects, those with asymptomatic AHR or asthma with controlled symptoms had a
      twofold increase in sodium influx and Na(i). Symptomatic asthmatics also had a
      twofold increase in sodium influx but a fourfold elevation of Na(i). Maximal
      Na(+)/K(+)-ATPase activity was reduced by half in symptomatic asthmatics compared
      with normal subjects. The reduction of maximal Na(+)/K(+)-ATPase activity was
      associated with a significant decrease in ATP turnover per Na(+)/K(+)-ATPase
      molecule but not number of Na(+)/K(+)-ATPase molecules per cell. In summary,
      airway hyperresponsiveness with or without asthma is associated with increased
      sodium influx and Na in leukocytes. Resting activity of Na(+)/K(+)-ATPase is also
      increased as a compensatory response to the increased sodium influx, but it is
      achieved at the expense of higher Na(i). Symptomatic asthma is additionally
      associated with reduction in maximal activity of Na(+)/K(+)-ATPase, resulting in
      reduced capacity to handle the increase in sodium influx and consequent severe
      elevations in Na(i).

PMID- 16465599
TI  - Lack of benefit of continuous positive airway pressure on lung function in
      patients with overlap syndrome.
AB  - Obstructive sleep apnea (OSA) has been shown to be an inflammatory stimulus and
      may potentially result in a deterioration in the respiratory status of patients
      with coexistent chronic obstructive pulmonary disease (COPD) (overlap syndrome).
      We hypothesized that with treatment of OSA, there would be an improvement in
      coexistent COPD in overlap patients. We also sought to characterize overlap
      patients by comparing them with patients with either OSA or COPD alone. We
      performed a retrospective study of patients who attended a university-affiliated
      Veterans Affairs hospital. Demographic and clinical data were obtained from the
      medical charts and pharmacy records for the preceding two years and for the two
      years following the initiation of continuous positive airway pressure (CPAP)
      therapy. Overlap patients had moderately severe sleep apnea (AHI 28.6 +/- 4.2)
      and moderately severe COPD (FEV1= 1.94 +/- 0.10 L). The prevalence of overlap
      syndrome in COPD patients was 11.9%, and 41% in OSA patients. Overlap patients
      who were compliant with CPAP therapy experienced a greater decrease in FEV1,
      percent predicted FEV1, percent decrease in FEV1, FVC, percent predicted FVC, and
      percent decrease in FVC when compared with noncompliant patients. A very strong
      correlation was found between the average hours of CPAP use per day and the
      percent decrease in FEV1 (r = 0.69, p = 0.003). There was a similar strong
      correlation for the decrease in FEV1 and percent predicted FEV1. OSA is common in
      COPD patients; similarly, COPD is common in OSA patients. Treatment of OSA with
      CPAP therapy in patients with overlap syndrome may not lead to an improvement in
      the coexistent COPD.

PMID- 16465600
TI  - A phase II study of the docetaxel-carboplatin chemotherapy regimen in advanced
      non-small-cell lung cancer.
AB  - The efficacy of the docetaxel-carboplatin combination chemotherapy was studied in
      various phase II studies. Based on these data we aimed to test the regimen in
      previously untreated patients with advanced advanced non-smoking lung cancer
      (NSCLC) with docetaxel 80 mg/m2 a standard dose of carboplatin at AUC = 5, in an
      attempt to define the efficacy and tolerability of the combination in an open
      label phase II study. Patients with histologically confirmed advanced NSCLC stage
      IIIB and IV were candidates for the present study. Docetaxel was administered at
      80 mg/m2 over 1 h by intravenous (IV) infusion followed by carboplatin AUC = 5 in
      30 min IV infusion, both on day 1, and recycled every 21 days. Sixty patients
      received 263 courses of therapy in total; 231/263 (88%) were administered
      according to the planned doses, and 48/60 (80%) patients received chemotherapy
      without decrement of the dose; 32/263 (12%) of the courses were administered with
      a 10%-30% dose reduction. Complete responses (CR) were seen in 5 patients (8.3%)
      and partial responses (PR) in 16 patients (26.7%) for an overall response rate of
      35%. Median duration of response was 7.5 months [95% confidence interval (CI)-7.1
      7.9], time to progression (TIP) 11.5 months (95% CI-8.2-14.8), median overall
      survival (OS) 15.0 months (95% CI-10.8-19.2). One-year survival was 61.7%.
      Toxicity was acceptable; it was calculated according to the administered cycles
      and was mainly neutropenia: grade 3, 9% and grade 4, 2%; anemia: grade 3, 8%;
      nausea and vomiting: grade 3, 8%. The outpatient regimen of docetaxel-carboplatin
      is effective with acceptable toxicity in patients with advanced NSCLC.

PMID- 16465601
TI  - Pleural aspergillosis with bronchopleurocutaneous fistula and costal bone
      destruction: a case report.
AB  - A 65-year-old man who, when young, had had tuberculosis treated by therapeutic
      pneumothorax, consulted his family physician for a constitutional syndrome and
      dyspnea. At this time radiologic studies showed left pleural effusion with
      bilateral calcified plaques, an infiltrate in the upper left lobe, and a picture
      compatible with aspergilloma, all suggesting semi-invasive aspergillosis. The
      patient failed to show up for his followup visit, so no therapy could be started
      or further diagnostic tests ordered. One month later he was admitted to this
      hospital for a bronchopleural fistula (empyema necessitatis) with subsequent
      spontaneous hydropneumothorax and costal bone involvement. The patient underwent
      surgery because of his rapid worsening condition. Biopsy examination revealed a
      large pleural aspergilloma. Despite immediate antifungal therapy, the patient
      died. We believe this to be the first report of pleural Aspergillus with a
      bronchopleurocutaneous fistula and costal bone destruction.

PMID- 16465603
TI  - Mean airway pressure and response to inhaled nitric oxide in neonatal and
      pediatric patients.
AB  - Inhaled nitric oxide (iNO) can improve oxygenation and ventilation-perfusion
      (V/Q) matching by reduction of shunt (Qs/Qt) in patients with hypoxemic lung
      disease. Because the improvement in V/Q matching must occur by redistribution of
      pulmonary blood flow, and because high airway pressure (Paw) increases
      physiologic dead space (Vd/Vt), we hypothesized that high Paw may limit the
      improvement in V/Q matching during iNO treatment. iNO 0-50 ppm was administered
      during mechanical ventilation. Mechanical ventilator settings were at the
      discretion of the attending physician. Qs/Qt and Vd/Vt were derived from a
      tripartite lung model with correction for shunt-induced dead space. Data from 62
      patients during 153 trials were analyzed for effects of Paw and iNO on Qs/Qt and
      Vd/Vt. Baseline Qs/Qt was slightly increased at Paw 16-23 cmH2O (p < 0.05), while
      Vd/Vt increased progressively with higher Paw (p < 0.002). Therapy with iNO
      significantly reduced Qs/Qt (p < 0.001) at all levels of mean Paw, reaching a
      maximum reduction at 16-23 cmH2O (p < 0.05), such that Qs/Qt during iNO treatment
      was similar at all levels of Paw. During iNO treatment, a reduction in Vd/Vt
      occurred only at Paw of 8-15 cmH2O (p < 0.05), and the positive relationship
      between Vd/Vt and Paw was maintained. These differential effects on Qs/Qt and
      Vd/Vt suggest that both high and low Paw may limit improvement in gas exchange
      with iNO. Analysis of gas exchange using this corrected tripartite lung model may
      help optimize ventilatory strategies during iNO therapy.

PMID- 16465609
TI  - Rheumatoid arthritis: a disease of chronic, low-amplitude signals transduced
      through T cell antigen receptors?
AB  - Technology has advanced to the stage where it is now possible to identify genes
      that confer low to moderate risk of developing autoimmune diseases such as
      rheumatoid arthritis (RA). This has been facilitated by the growing appreciation
      that these hard to detect genetic signals can only be defined in large cohorts of
      well characterized patients. In RA, the association between disease
      susceptibility and genes encoded within the MHC has been known for decades.
      Recent studies have identified several new candidate genes that provide further
      insights into the molecular nature of aberrant immune responses in chronic
      inflammatory diseases. Here, we describe some of these new genes. Based on their
      known functions we propose that in a subgroup of patients with RA inheritance of
      allelic variants at distinct loci could lead to dysregulation of adaptive immune
      responses characterized by chronic, low-amplitude signaling transduced by antigen
      T cell receptors.

PMID- 16465610
TI  - The role of macrophage migration inhibitory factor in the inflammatory immune
      response and rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a debilitating disease of unknown etiology. Although
      the pathogenesis of RA is multifactorial, the contribution of cytokines is
      undoubtedly pivotal in the progression of the inflammatory process. One cytokine
      gaining recognition for its importance in inflammation is macrophage migration
      inhibitory factor (MIF). Initially described as a biological activity, a broad
      range of functions of MIF has emerged including induction of proinflammatory
      mediators as well as demonstrated roles in both innate and adaptive immunity. In
      RA, increased MIF levels have been demonstrated in serum, synovial fluid and
      tissue with the latter correlating with disease activity. In vitro, MIF induces
      production of key proinflammatory genes operative in arthritis, including IL-1,
      TNF, IL-6, IL-8, COX-2, PLA2, and MMPs. In addition, MIF regulates proliferation
      and apoptosis via direct effects on the tumor suppressor protein p53 implicating
      a role for MIF in synovial hyperplasia. In vivo, MIF antagonism or MIF deficiency
      result in decreased disease severity in animal models of RA further confirming a
      role for MIF in joint inflammation. Interestingly, MIF is induced by
      glucocorticoids and MIF in turn antagonises glucocorticoid effects. This unique
      relationship presents antagonism of MIF as a potentially effective steroid
      sparing therapy.

PMID- 16465611
TI  - The pivotal nature of sugars in normal physiology and disease.
AB  - Glycopathology has become the focus of considerable research in recent years as
      the role of glycosylation in the development, regulation, and progression of
      disease has come under increased scrutiny. Cracking the 'sugar-code' in
      biological systems that relate to both health and disease holds tremendous
      promise for deciphering disease mechanisms such as the link between the
      glycomodification of immunoglobulins and various autoimmune diseases, notably IgG
      in rheumatoid arthritis (RA), and has exciting implications for the development
      of novel diagnostic and therapeutic interventions.

PMID- 16465602
TI  - Mechanism of endothelin-1 activation of MAP kinases in neonatal pulmonary
      vascular smooth muscle.
AB  - Mitogen-activated protein kinases (MAPKs) belong to the group of serine-threonine
      kinases that are rapidly activated in response to growth factor stimulation. In
      adult mammalian cells, the MAPK family includes extracellular signal-regulated
      kinases 1 and 2 (ERK1 and ERK2 or p44(mapk) and p42(mapk)), which translocate to
      the nucleus and integrate signals from second messengers leading to cellular
      proliferation or differentiation, but the specific role of MAPKs in neonatal
      pulmonary vascular smooth muscle is not well understood. Expression of p44(mapk)
      and p42(mapk) in primary cultured pulmonary vascular smooth muscle cells from
      neonatal (1-2 day old) rats was identified by Western immunoblot analysis and
      treatment with 10 nM endothelin-1 (ET-1), a potent vasoconstrictor with vascular
      mitogenic properties, induced cell proliferation, and phosphorylation of both
      p44(mapk) and p42(mapk). The protein kinase C (PKC) isozyme inhibitor (alpha,
      beta, gamma, delta, zeta) Go 6983, the ET(A) receptor antagonist BQ 123, and the
      MAPK kinase inhibitor PD98059 blocked the cell proliferation response to ET-1.
      Also, BQ 123, Go 6983, and PKC inhibitor 20-28 (Myr-N-FARKGAL-RQ-NH2-PKCalpha
      antagonist) inhibited ET-1-induced phosphorylation of both p44(mapk) and
      p42(mapk). In contrast, the reactive oxygen species (ROS) inhibitor diphenylene
      iodonium (DPI), the PKCdelta inhibitor rottlerin, and the ET(B) receptor
      antagonist BQ 788 did not block ET-1-induced phosphorylation of MAPKs.
      Collectively, these data demonstrate the expression and phosphorylation of MAPKs
      by ET-1 and suggests that MAPK activation and cell proliferation by ET-1 occurs
      via ET(A) receptor stimulation and specific PKC isozyme activation in rat
      neonatal pulmonary vascular smooth muscle.

PMID- 16465612
TI  - Rheumatoid arthritis: inflammation and bone loss.
AB  - Chronic synovial inflammation is usually accompanied by bone erosion. Due to
      resulting structural damage, bone erosion is a major reason for disability in RA
      patients. Anti-rheumatic drug therapy is focussed not only on the control of
      synovial inflammation but also on preserving bone from structural damage. Bone
      erosion in arthritis is a consequence of synovial osteoclast formation.
      Therapeutic approaches which interfere with synovial osteoclastogenesis and/or
      osteoclast activation are therefore of great interest. This review describes the
      mechanism of inflammatory bone loss, describes its cellular and molecular players
      and gives insights in current therapeutic tools to inhibit this process.

PMID- 16465613
TI  - Rheumatoid arthritis: links with cardiovascular disease and the receptor for
      advanced glycation end products.
AB  - Cardiovascular (CV) disease is increased in patients with chronic inflammatory
      disease, including rheumatoid arthritis (RA). Furthermore it has become clear at
      a pathophysiological level, that atherosclerosis has striking similarities with
      autoimmune disease. This realization has come at a time of paradigm shift in how
      rheumatologists manage RA, with the availability of biological agents targeting
      key inflammatory cytokines. This review will focus on the possible causes of
      increased vascular disease in RA, including the role of traditional CV risk
      factors. Mechanisms potentially at play, such as C-reactive protein (CRP),
      altered coagulation, and cyclooxygenase (COX)-2 inhibitors will be covered in
      brief. The receptor for advanced glycation end products (RAGE) has been
      identified as a candidate molecule influencing response to ongoing inflammation
      and autoimmunity. There will be a focus on the role of RAGE in CV disease and RA.
      As has been the case with many novel molecules, functional polymorphisms are
      thought to alter disease expression and assist us in coming to terms with the
      biological activities of the parent molecule. The review will conclude with a
      discussion of the potential role of the RAGE Glycine 82 Serine polymorphism.

PMID- 16465614
TI  - Targeted therapy in rheumatoid arthritis.
AB  - The approach of targeting cytokines has dramatically improved the success in the
      treatment of rheumatoid arthritis (RA). The blocking of tumor necrosis factor
      (TNF)-alpha or interleukin (IL)-1 is well established in clinical practice, but a
      lack or loss of clinical response still occurs in up to 30% of RA patients.
      Therefore, enhanced efforts must be made to develop new strategies to disrupt the
      inflammatory process and to inhibit synovitis and joint destruction. In this
      respect, the blocking of IL-6 receptor with tocilizumab, the prevention of
      costimulatory T cell signals by abatacept, or targeting B cells with rituximab
      look promising in clinical trials. Furthermore, blocking intracellular signal
      transduction broadens the spectrum of targeted therapy. This article reviews
      recent clinical aspects of established anti-cytokine therapies and gives an
      insight into the experimental and clinical development of new specifically acting
      drugs.

PMID- 16465615
TI  - Treatment of rheumatoid arthritis in the 21st century: targeting B-lymphocytes.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      persistent inflammation of synovial tissue. Although the initiating event of RA
      is still unknown, recent research has demonstrated the importance of the
      increased production of tumor necrosis factor (TNF) alpha in the perpetuation of
      the inflammatory process of this disease. Targeting this molecule with soluble
      receptors, i.e., etanercept, or antibodies, like infliximab or adalimumab, a new
      class of highly effective anti rheumatic drugs has been developed. Unfortunately,
      not all patients respond sufficiently to TNF blockade and some of the patients
      become unresponsive to TNF-blocking agents. Targeting B-lymphocytes in these
      patients has opened a new therapeutic window. It has been demonstrated that B
      lymphocytes have an important impact in the pathophysiology of RA. These cells
      produce not only a variety of autoantibodies, but directly stimulate
      autoaggressive T lymphocytes in the synovium. Furthermore, B-lymphocytes produce
      a variety of proinflammatory cytokines that also activate monocytes and
      synoviocytes. Several placebo-controlled clinical trials have demonstrated the
      efficacy of B-lymphocyte-directed therapy in patients that have responded poorly
      to conventional disease-modifying drugs or TNF blockade. In addition, several
      other B-cell specific antigens are potential targets in different autoimmune
      diseases.

PMID- 16465617
TI  - An ancient balanced polymorphism in a regulatory region of human major
      histocompatibility complex is retained in Chinese minorities but lost worldwide.
AB  - The coding regions of many of the major histocompatibility complex (MHC) (human
      leukocyte antigen [HLA] in humans) molecules are believed to be subject to
      balancing selection. But it is less certain whether the regulatory regions of
      such coding sequences are also subject to the same type of selection. Here, we
      studied the polymorphism of the regulatory regions of the HLA-DPA1 and HLA-DPB1
      genes among ethnic minorities in southwestern China. Phylogenetic analysis
      revealed two deep clades >10 million years old. There is almost complete linkage
      disequilibrium between the regulatory and coding regions of HLA-DPA1, which hints
      at coadaptive balancing selection on the entire region. Thus, the molecular
      mechanism of balancing selection in MHC may involve expression modulation in
      addition to coding-region polymorphisms. Although the frequency of clade II is
      >30% in some ethnic minorities, it decreases to <5% among southern Han Chinese
      and vanishes among Europeans. As suspected, some ancient balanced polymorphisms,
      lost in major populations, still exist in isolated ethnicities. These isolated
      populations may thus contribute disproportionately to the total diversity of
      modern humans.

PMID- 16465618
TI  - Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error
      of metabolism.
AB  - N-terminal acetylation of proteins is a widespread and highly conserved process.
      Aminoacylase 1 (ACY1; EC 3.5.14) is the most abundant of the aminoacylases, a
      class of enzymes involved in hydrolysis of N-acetylated proteins. Here, we
      present four children with genetic deficiency of ACY1. They were identified
      through organic acid analyses using gas chromatography-mass spectrometry,
      revealing increased urinary excretion of several N-acetylated amino acids,
      including the derivatives of methionine, glutamic acid, alanine, leucine,
      glycine, valine, and isoleucine. Nuclear magnetic resonance spectroscopy analysis
      of urine samples detected a distinct pattern of N-acetylated metabolites,
      consistent with ACY1 dysfunction. Functional analyses of patients' lymphoblasts
      demonstrated ACY1 deficiency. Mutation analysis uncovered recessive loss-of
      function or missense ACY1 mutations in all four individuals affected. We conclude
      that ACY1 mutations in these children led to functional ACY1 deficiency and
      excretion of N-acetylated amino acids. Questions remain, however, as to the
      clinical significance of ACY1 deficiency. The ACY1-deficient individuals were
      ascertained through urine metabolic screening because of unspecific psychomotor
      delay (one subject), psychomotor delay with atrophy of the vermis and
      syringomyelia (one subject), marked muscular hypotonia (one subject), and follow
      up for early treated biotinidase deficiency and normal clinical findings (one
      subject). Because ACY1 is evolutionarily conserved in fish, frog, mouse, and
      human and is expressed in the central nervous system (CNS) in human, a role in
      CNS function or development is conceivable but has yet to be demonstrated. Thus,
      at this point, we cannot state whether ACY1 deficiency has pathogenic
      significance with pleiotropic clinical expression or is simply a biochemical
      variant. Awareness of this new genetic entity may help both in delineating its
      clinical significance and in avoiding erroneous diagnoses.

PMID- 16465619
TI  - A spectrum of PCSK9 alleles contributes to plasma levels of low-density
      lipoprotein cholesterol.
AB  - Selected missense mutations in the proprotein convertase subtilisin/kexin type 9
      serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia,
      whereas nonsense mutations in the same gene are associated with low plasma levels
      of low-density lipoprotein cholesterol (LDL-C). Here, DNA sequencing and chip
      based oligonucleotide hybridization were used to determine whether other sequence
      variations in PCSK9 contribute to differences in LDL-C levels. The coding regions
      of PCSK9 were sequenced in the blacks and whites from the Dallas Heart Study
      (n=3,543) who had the lowest (<5th percentile) and highest (>95th percentile)
      plasma levels of LDL-C. Of the 17 missense variants identified, 3 (R46L, L253F,
      and A443T) were significantly and reproducibly associated with lower plasma
      levels of LDL-C (reductions ranging from 3.5% to 30%). None of the low-LDL-C
      variants were associated with increased hepatic triglyceride content, as measured
      by proton magnetic resonance spectroscopy. This finding is most consistent with
      the reduction in LDL-C being caused primarily by accelerating LDL clearance,
      rather than by reduced lipoprotein production. Association studies with 93
      noncoding single-nucleotide polymorphisms (SNPs) at the PCSK9 locus identified 3
      SNPs associated with modest differences in plasma LDL-C levels. Thus, a spectrum
      of sequence variations ranging in frequency (from 0.2% to 34%) and magnitude of
      effect (from a 3% increase to a 49% decrease) contribute to interindividual
      differences in LDL-C levels. These findings reveal that PCSK9 activity is a major
      determinant of plasma levels of LDL-C in humans and make it an attractive
      therapeutic target for LDL-C lowering.

PMID- 16465620
TI  - A comparison of phasing algorithms for trios and unrelated individuals.
AB  - Knowledge of haplotype phase is valuable for many analysis methods in the study
      of disease, population, and evolutionary genetics. Considerable research effort
      has been devoted to the development of statistical and computational methods that
      infer haplotype phase from genotype data. Although a substantial number of such
      methods have been developed, they have focused principally on inference from
      unrelated individuals, and comparisons between methods have been rather limited.
      Here, we describe the extension of five leading algorithms for phase inference
      for handling father-mother-child trios. We performed a comprehensive assessment
      of the methods applied to both trios and to unrelated individuals, with a focus
      on genomic-scale problems, using both simulated data and data from the HapMap
      project. The most accurate algorithm was PHASE (v2.1). For this method, the
      percentages of genotypes whose phase was incorrectly inferred were 0.12%, 0.05%,
      and 0.16% for trios from simulated data, HapMap Centre d'Etude du Polymorphisme
      Humain (CEPH) trios, and HapMap Yoruban trios, respectively, and 5.2% and 5.9%
      for unrelated individuals in simulated data and the HapMap CEPH data,
      respectively. The other methods considered in this work had comparable but
      slightly worse error rates. The error rates for trios are similar to the levels
      of genotyping error and missing data expected. We thus conclude that all the
      methods considered will provide highly accurate estimates of haplotypes when
      applied to trio data sets. Running times differ substantially between methods.
      Although it is one of the slowest methods, PHASE (v2.1) was used to infer
      haplotypes for the 1 million-SNP HapMap data set. Finally, we evaluated methods
      of estimating the value of r(2) between a pair of SNPs and concluded that all
      methods estimated r(2) well when the estimated value was >or=0.8.

PMID- 16465621
TI  - Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler
      polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha /
      beta -subunits precursor gene.
AB  - Mucolipidosis II (MLII; I-cell disease) and mucolipidosis IIIA (MLIIIA; classical
      pseudo-Hurler polydystrophy) are diseases in which the activity of the uridine
      diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1
      phosphotransferase (GlcNAc-phosphotransferase) is absent or reduced,
      respectively. In the absence of mannose phosphorylation, trafficking of lysosomal
      hydrolases to the lysosome is impaired. In these diseases, mistargeted lysosomal
      hydrolases are secreted into the blood, resulting in lysosomal deficiency of many
      hydrolases and a storage-disease phenotype. To determine whether these diseases
      are caused by mutations in the GlcNAc-phosphotransferase alpha / beta -subunits
      precursor gene (GNPTAB), we sequenced GNPTAB exons and flanking intronic
      sequences and measured GlcNAc-phosphotransferase activity in patient fibroblasts.
      We identified 15 different mutations in GNPTAB from 18 pedigrees with MLII or
      MLIIIA and demonstrated that these two diseases are allelic. Mutations in both
      alleles were identified in each case, which demonstrated that GNPTAB mutations
      are the cause of both diseases. Some pedigrees had identical mutations. One
      frameshift mutation (truncation at amino acid 1171) predominated and was found in
      both MLII and MLIIIA. This mutation was found in combination with severe
      mutations (i.e., mutations preventing the generation of active enzyme) in MLII
      and with mild mutations (i.e., mutations allowing the generation of active
      enzyme) in MLIIIA. Some cases of MLII and MLIIIA were the result of mutations
      that cause aberrant splicing. Substitutions were inside the invariant splice-site
      sequence in MLII and were outside it in MLIIIA. When the mutations were analyzed
      along with GlcNAc-phosphotransferase activity, it was possible to confidently
      distinguish these two clinically related but distinct diseases. We propose
      criteria for distinguishing these two disorders by a combination of mutation
      detection and GlcNAc-phosphotransferase activity determination.

PMID- 16465622
TI  - Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle
      control genes.
AB  - The candidate-gene approach in association studies of polygenic diseases has
      often yielded conflicting results. In this hospital-based case-control study with
      696 white patients newly diagnosed with bladder cancer and 629 unaffected white
      controls, we applied a multigenic approach to examine the associations with
      bladder cancer risk of a comprehensive panel of 44 selected polymorphisms in two
      pathways, DNA repair and cell-cycle control, and to evaluate higher-order gene
      gene interactions, using classification and regression tree (CART) analysis.
      Individually, only XPD Asp312Asn, RAG1 Lys820Arg, and a p53 intronic SNP
      exhibited statistically significant main effects. However, we found a significant
      gene-dosage effect for increasing numbers of potential high-risk alleles in DNA
      repair and cell-cycle pathways separately and combined. For the nucleotide
      excision repair pathway, compared with the referent group (fewer than four
      adverse alleles), individuals with four (odds ratio [OR] = 1.52, 95% CI 1.05
      2.20), five to six (OR = 1.81, 95% CI 1.31-2.50), and seven or more adverse
      alleles (OR = 2.50, 95% CI 1.69-3.70) had increasingly elevated risks of bladder
      cancer (P for trend <.001). Each additional adverse allele was associated with a
      1.21-fold increase in risk (95% CI 1.12-1.29). For the combined analysis of DNA
      repair and cell-cycle SNPs, compared with the referent group (<13 adverse
      alleles), the ORs for individuals with 13-15, 16-17, and >or=18 adverse alleles
      were 1.22 (95% CI 0.84-1.76), 1.57 (95% CI 1.05-2.35), and 1.77 (95% CI 1.19
      2.63), respectively (P for trend = .002). Each additional high-risk allele was
      associated with a 1.07-fold significant increase in risk. In addition, we found
      that smoking had a significant multiplicative interaction with SNPs in the
      combined DNA-repair and cell-cycle-control pathways (P<.01). All genetic effects
      were evident only in "ever smokers" (persons who had smoked >or=100 cigarettes)
      and not in "never smokers." A cross-validation statistical method developed in
      this study confirmed the above observations. CART analysis revealed potential
      higher-order gene-gene and gene-smoking interactions and categorized a few higher
      risk subgroups for bladder cancer. Moreover, subgroups identified with higher
      cancer risk also exhibited higher levels of induced genetic damage than did
      subgroups with lower risk. There was a significant trend of higher numbers of
      bleomycin- and benzo[a]pyrene diol-epoxide (BPDE)-induced chromatid breaks (by
      mutagen-sensitivity assay) and DNA damage (by comet assay) for individuals in
      higher-risk subgroups among cases of bladder cancer in smokers. The P for the
      trend was .0348 for bleomycin-induced chromosome breaks, .0036 for BPDE-induced
      chromosome breaks, and .0397 for BPDE-induced DNA damage, indicating that these
      higher-order gene-gene and gene-smoking interactions included SNPs that modulated
      repair and resulted in diminished DNA-repair capacity. Thus, genotype/phenotype
      analyses support findings from CART analyses. This is the first comprehensive
      study to use a multigenic analysis for bladder cancer, and the data suggest that
      individuals with a higher number of genetic variations in DNA-repair and cell
      cycle-control genes are at an increased risk for bladder cancer, confirming the
      importance of taking a multigenic pathway-based approach to risk assessment.

PMID- 16465623
TI  - Improved power offered by a score test for linkage disequilibrium mapping of
      quantitative-trait loci by selective genotyping.
AB  - Selective genotyping is used to increase efficiency in genetic association
      studies of quantitative traits by genotyping only those individuals who deviate
      from the population mean. However, selection distorts the conditional
      distribution of the trait given genotype, and such data sets are usually analyzed
      using case-control methods, quantitative analysis within selected groups, or a
      combination of both. We show that Hotelling's T(2) test, recently proposed for
      association studies of one or several tagging single-nucleotide polymorphisms in
      a prospective (i.e., trait given genotype) design, can also be applied to the
      retrospective (i.e., genotype given trait) selective-genotyping design, and we
      use simulation to demonstrate its improved power over existing methods.

PMID- 16465625
TI  - Methicillin-resistant Staphylococcus aureus control: we didn't start the fire,
      but it's time to put it out.

PMID- 16465624
TI  - Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease.
AB  - Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized
      by progressive and disfiguring reticulate hyperpigmentation of the flexures. We
      performed a genomewide linkage analysis of two German families and mapped DDD to
      chromosome 12q, with a total LOD score of 4.42 ( theta =0.0) for marker D12S368.
      This region includes the keratin gene cluster, which we screened for mutations.
      We identified loss-of-function mutations in the keratin 5 gene (KRT5) in all
      affected family members and in six unrelated patients with DDD. These represent
      the first identified mutations that lead to haploinsufficiency in a keratin gene.
      The identification of loss-of-function mutations, along with the results from
      additional functional studies, suggest a crucial role for keratins in the
      organization of cell adhesion, melanosome uptake, organelle transport, and
      nuclear anchorage.

PMID- 16465626
TI  - What proportion of hospital patients colonized with methicillin-resistant
      Staphylococcus aureus are identified by clinical microbiological cultures?
AB  - BACKGROUND: Most hospitals in the United States do not perform active
      surveillance cultures and, thus, rely on clinical microbiological cultures (CMCs)
      to identify patients colonized with methicillin-resistant Staphylococcus aureus
      (MRSA). We sought to determine what proportion of patients who are colonized with
      MRSA at admission are identified by CMCs during hospitalization. METHODS: From
      February 1998 through November 2002, patients found to be colonized with MRSA at
      admission by use of active surveillance cultures were identified. The proportion
      of colonized patients who had a CMC that was positive for MRSA, the number of
      CMCs performed and their type (ie, according to the anatomical site from which
      specimens were obtained for culture), and the number and type of CMCs that were
      positive for MRSA were calculated. RESULTS: Four hundred thirty-seven patients
      were found to be colonized with MRSA at admission, and 98 of 1,238 CMCs (7.9%;
      95% confidence interval, 6.5%-9.6%) performed for 66 of these patients (15%; 95%
      confidence interval, 11.9%-18.8%) were positive for MRSA. The number of
      nonisolated days that would have occurred by relying on CMCs to identify MRSA
      colonized patients was 3,247 (mean, 7.4 days per patient). Among the anatomical
      sites from which specimens were obtained for CMC, wounds demonstrated the highest
      sensitivity (30.2%) for identifying MRSA-colonized patients. CONCLUSIONS: CMCs
      failed to identify 85% of MRSA-colonized patients, because, in part, CMCs
      identified only a small proportion of colonized patients. Because many studies
      have shown a decrease in the transmission of MRSA from colonized patients for
      whom contact precautions, rather than standard precautions, are used, the
      findings of this study suggest that failure to identify colonized patients and to
      use contact precautions may be an important reason for the increasing rate of
      nosocomial MRSA infection in hospitals in the United States.

PMID- 16465627
TI  - Impact of an aggressive infection control strategy on endemic Staphylococcus
      aureus infection in liver transplant recipients.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus has emerged as a leading
      pathogen in transplant recipients and has become endemic in many institutions
      where transplantation is performed. The role of active surveillance programs
      based on the detection of colonization in the prevention of S. aureus infection
      in liver transplant recipients has not been defined. METHODS: A total of 47
      consecutive patients who underwent liver transplantation during 1996-1999 were
      compared with 97 patients who received a liver transplant during 2000-2004 after
      implementation of an intensive intervention program that included use of
      surveillance cultures to detect nasal and rectal colonization, use of cohorting
      and contact isolation precautions, and decolonization with intranasal mupirocin
      therapy. RESULTS: The rate of new acquisition of S. aureus colonization of nares
      after transplantation decreased from 45.6% (21 of 46 patients) during the
      preintervention period to 9.9% (9 of 91 patients) during the postintervention
      period (P<.001). An increased length of hospital stay (odds ratio, 1.03; 95%
      confidence interval, 1.01-1.05; P<.002) was associated with new carriage
      acquisition, and transplantation during the postintervention period (odds ratio,
      0.21; 95% confidence interval, 0.08-0.51; P<.001) was independently protective
      against new carriage. The rate of infection due to S. aureus decreased from 40.4%
      (19 of 47 patients) during the preintervention period to 4.1% (4 of 97 patients)
      during the postintervention period (P<.001), and the rate of bacteremia decreased
      from 25.5% (12 of 47 patients) to 4.1% (4 of 97 patients), respectively (P<.001).
      Overall, S. aureus infections occurred more frequently among patients with new
      carriage than among patients who were carriers at the time of transplantation
      (P<.001) or patients who were noncarriers (P<.001). CONCLUSIONS: Use of active
      surveillance cultures to detect colonization and implementation of targeted
      infection control interventions proved to be effective in curtailing new
      acquisition of S. aureus colonization and in decreasing the rate of S. aureus
      infection that was endemic in our population of liver transplant recipients.

PMID- 16465628
TI  - A study of the relationship between environmental contamination with methicillin
      resistant Staphylococcus aureus (MRSA) and patients' acquisition of MRSA.
AB  - OBJECTIVE: The study aimed to examine the presence of methicillin-resistant
      Staphylococcus aureus (MRSA) in the environment and its relationship to patients'
      acquisition of MRSA. DESIGN: A prospective study was conducted in a 9-bed
      intensive care unit for 14 months. At every environmental screening, samples were
      obtained from the same 4 sites in each bed space. Patients were screened at
      admission and then 3 times weekly. All environmental and patient strains were
      typed using pulsed-field gel electrophoresis. RESULTS: MRSA was isolated from the
      environment at every environmental screening, when both small and large numbers
      of patients were colonized. Detailed epidemiological typing of 250 environmental
      and 139 patient isolates revealed 14 different pulsed-field gel electrophoresis
      profiles, with variants of EMRSA-15 being the predominant type. On only 20
      (35.7%) of 56 occasions were the strains isolated from the patients and the
      strains isolated from their immediate environment indistinguishable. There was
      strong evidence to suggest that 3 of 26 patients who acquired MRSA while in the
      intensive care unit acquired MRSA from the environment. CONCLUSIONS: This study
      reveals widespread contamination of the hospital environment with MRSA,
      highlights the complexities of the problem of contamination, and confirms the
      need for more-effective cleaning of the hospital environment to eliminate MRSA.

PMID- 16465629
TI  - Clinical and laboratory features of community-associated methicillin-resistant
      Staphylococcus aureus: is it really new?
AB  - OBJECTIVE: To review the epidemiologic and molecular characteristics of community
      associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Detroit,
      Michigan, to assess the risk factors for infection and the response to therapy.
      DESIGN: Prospective clinical and laboratory study of 2003-2004 CA-MRSA isolates.
      Molecular features were compared with CA-MRSA isolates from 1980. SETTING: A 600
      bed urban academic medical center. PATIENTS: Twenty-three patients with CA-MRSA
      infections from 2003-2004 were evaluated. In addition, laboratory analysis was
      performed on 13 CA-MRSA isolates from 1980. MAIN OUTCOME MEASURES: Laboratory
      analysis of isolates included antimicrobial susceptibility testing, pulsed-field
      genotyping, testing for Panton-Valentine leukocidin (PVL) genes, and
      staphylococcal cassette chromosome mec typing. RESULTS: Patients were
      predominantly young African American males and presented with skin and soft
      tissue infections. All isolates were resistant to erythromycin and highly
      susceptible to other agents. Patients were generally treated successfully with
      combination incision and drainage and systemic antibiotics. Among the 23
      isolates, 20 (87%) were the same strain. This strain carried the staphylococcal
      cassette chromosome mec type IV and PVL genes and is genetically identical to USA
      300. Thirteen isolates of patients from our community who presented with CA-MRSA
      infections in 1980 represented a single clone that is unique compared with the
      2003-2004 isolates. This strain carried staphylococcal cassette chromosome mec
      type IVA but did not carry the PVL genes. CONCLUSIONS: In our community, CA-MRSA
      is largely due to a single clone with a type IV mec gene and PVL gene. The type
      IV staphylococcal cassette chromosome mec type can be demonstrated in CA-MRSA
      isolates from a remote period, suggesting that earlier outbreaks were not related
      to healthcare exposure.

PMID- 16465630
TI  - Management of outbreaks of methicillin-resistant Staphylococcus aureus infection
      in the neonatal intensive care unit: a consensus statement.
AB  - OBJECTIVE: In 2002, the Chicago Department of Public Health (CDPH; Chicago,
      Illinois) convened the Chicago-Area Neonatal MRSA Working Group (CANMWG) to
      discuss and compare approaches aimed at control of methicillin-resistant
      Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs). To better
      understand these issues on a regional level, the CDPH and the Evanston Department
      of Health and Human Services (EDHHS; Evanston, Illinois) began an investigation.
      DESIGN: Survey to collect demographic, clinical, microbiologic, and epidemiologic
      data on individual cases and clusters of MRSA infection; an additional survey
      collected data on infection control practices. SETTING: Level III NICUs at
      Chicago-area hospitals. PARTICIPANTS: Neonates and healthcare workers associated
      with the level III NICUs. METHODS: From June 2001 through September 2002, the
      participating hospitals reported all clusters of MRSA infection in their
      respective level III NICUs to the CDPH and the EDHHS. RESULTS: Thirteen clusters
      of MRSA infection were detected in level III NICUs, and 149 MRSA-positive infants
      were reported. Infection control surveys showed that hospitals took different
      approaches for controlling MRSA colonization and infection in NICUs. CONCLUSION:
      The CANMWG developed recommendations for the prevention and control of MRSA
      colonization and infection in the NICU and agreed that recommendations should
      expand to include future data generated by further studies. Continuing
      partnerships between hospital infection control personnel and public health
      professionals will be crucial in honing appropriate guidelines for effective
      approaches to the management and control of MRSA colonization and infection in
      NICUs.

PMID- 16465631
TI  - Methicillin-resistant Staphylococcus aureus in German intensive care units during
      2000-2003: data from Project SARI (Surveillance of Antimicrobial Use and
      Antimicrobial Resistance in Intensive Care Units).
AB  - OBJECTIVES: The objective of this study was to analyze methicillin-resistant
      Staphylococcus aureus (MRSA) percentages (defined as the percentage of S. aureus
      isolates that are resistant to methicillin) and antimicrobial consumption in
      intensive care units (ICUs) participating in Project SARI (Surveillance of
      Antimicrobial Use and Antimicrobial Resistance in Intensive Care Units), to look
      for temporal changes in MRSA percentages and antimicrobial consumption in
      individual ICUs as an indicator of the impact of an active surveillance system,
      and to investigate the differences between ICUs with increased MRSA percentages
      versus those with decreased percentages during a period of 3 years (2001-2003).
      METHODS: This was a prospective, ICU-based and laboratory-based surveillance
      study involving 38 German ICUs during 2000-2003. Antimicrobial use was reported
      in terms of defined daily doses (DDDs) per 1,000 patient-days. Temporal changes
      in the MRSA percentage and antimicrobial use in individual ICUs were calculated
      by means of the Wilcoxon signed rank test. The incidence density of nosocomial
      MRSA infection was defined as the number of nosocomial MRSA infections per 1,000
      patient-days. RESULTS: From February 2000 through December 2003, a total of 38
      ICUs reported data on 499,694 patient-days and 9,552 S. aureus isolates,
      including 2,249 MRSA isolates and 660,029 DDDs of antimicrobials. Cumulative MRSA
      percentages ranged from 0% to 64.4%, with a mean of 23.6%. The MRSA incidence
      density ranged from 0 to 38.2 isolates per 1,000 patient-days, with a mean of
      2.77 isolates per 1,000 patient-days. There was a positive correlation between
      MRSA percentage and imipenem and ciprofloxacin use (P<.05). Overall, comparison
      of data from 2001 with data from 2003 showed that MRSA percentages increased in
      18 ICUs (median increase, 13.2% [range, 1.6%-38.4%]) and decreased in 14 ICUs
      (median decrease, 12% [range, 1.0%-48.4%]). Increased use of third-generation
      cephalosporins, glycopeptides, or aminoglycosides correlated significantly with
      an increase in the MRSA percentage (P<.05). The cumulative nosocomial MRSA
      infection incidence density for 141 ICUs that did not participate in SARI and,
      therefore, did not receive feedback increased from 0.26 to 0.35 infections per
      1,000 patient-days during a 3-year period, whereas the rate in SARI ICUs
      decreased from 0.63 to 0.40 infections per 1,000 patient-days. CONCLUSION: The
      MRSA situation in German ICUs is still heterogeneous. Because MRSA percentages
      range from 0% to 64.4%, further studies are required to confirm findings that no
      change in the MRSA percentage and a decrease in the nosocomial MRSA infection
      incidence density in SARI ICUs reflect the impact of an active surveillance
      system.

PMID- 16465632
TI  - Evaluation of an intervention designed to decrease the rate of nosocomial
      methicillin-resistant Staphylococcus aureus infection by encouraging decreased
      fluoroquinolone use.
AB  - OBJECTIVE: Society for Health Care Epidemiology guidelines recommend decreasing
      the use of fluoroquinolone antibiotics in institutions where methicillin
      resistant Staphylococcus aureus (MRSA) is endemic. We evaluated whether an
      intervention to limit fluoroquinolone use was associated with a lower rate of
      nosocomial MRSA infection and summarized changes in antibiotic use, changes in
      other variables potentially correlated with a lower rate of MRSA infection, and
      rates of nosocomial infections due to other pathogens. DESIGN: Single-center
      quasi-experimental design. A time series of nosocomial MRSA infections was
      measured at monthly intervals from July 2001 through June of 2004; there were 80
      MRSA infections recorded. Segmented regression analysis (ie, quasi-Poisson
      generalized linear models) was used to evaluate variables possibly associated
      with the nosocomial MRSA infection rate. SETTING: An 87-bed Veterans Affairs
      teaching hospital with an extended-care facility. INTERVENTION: A physician
      directed computer-generated intervention designed to limit the use of
      fluoroquinolone antibiotics was initiated, and institutional changes in
      antibiotic use and nosocomial MRSA infection rates were tracked. RESULTS: After
      the intervention, fluoroquinolone use decreased by approximately 34%, and
      levofloxacin use decreased by approximately 50%. Decreased fluoroquinolone use
      was offset by increased cephalosporin, piperacillin-tazobactam, and trimethoprim
      sulfamethoxazole use. The nosocomial MRSA infection rate decreased from 1.37 to
      0.63 episodes per 1,000 patient-days after the study intervention (P=.02).
      Coagulase-negative Staphylococcus and Enterococcus infection rates also
      decreased. However, the rate of infection with gram-negative organisms increased.
      The rate of MRSA infection was positively correlated with levofloxacin use
      (P=.01) and azithromycin use (P=.08), whereas it was negatively correlated with
      summer season (P=.05). In a subsequent model, the rate of MRSA infection was
      negatively correlated with the study intervention (P=.04). CONCLUSION: Reduction
      in the institutional use of fluoroquinolones may be associated with a lower
      nosocomial MRSA infection rate.

PMID- 16465633
TI  - The role of institutional epidemiologic weight in guiding infection surveillance
      and control in community and hospital populations.
AB  - BACKGROUND: Institutions such as hospitals, prisons, and long-term care
      facilities have been identified as focal points for the transmission of emerging
      infections. Cost-effective control of these infections in large populations
      requires the identification of optimal subpopulations for targeted infection
      control interventions. Our objective was to quantify and compare the relative
      impact that individual institutions or subpopulations have on wider population
      level outbreaks of emerging pathogens. DESIGN: We describe a simple mathematical
      model to compute the epidemiologic weight (EW) of an institution or
      subpopulation. The EW represents the rate at which newly infectious individuals
      exit the institution under consideration. SETTING: A hypothetical academic
      tertiary-care hospital (700 beds, 5-day length of stay [LOS]) and prison (3098
      inmates, 27-day LOS). PATIENTS: Individuals entering a hospital in-patient prison
      ward and nonprisoners entering both medical and surgical intensive-care units and
      those admitted to the general medical and surgical wards. RESULTS: The recent
      example of the community-acquired methicillin-resistant Staphylococcus aureus
      epidemic is used to illustrate the EW calculation. Hospitals and prisons, which
      often have vastly dissimilar populations sizes and LOSs and might have differing
      transmission rates, can have comparable EWs and thus contribute equally to an
      epidemic in the community. CONCLUSIONS: This method highlights the importance of
      measuring entrance and exit colonization prevalences for the optimal targeting of
      prevention measures. The EW not only identified superspreader institutions but
      also ranks them, enabling public health workers to optimize the allocation of
      resources to places where they are likely to be of most benefit.

PMID- 16465634
TI  - Nurses and occupational exposures to bloodborne viruses in Poland.
AB  - STUDY OBJECTIVE: To record descriptions of occupational exposures to blood,
      determine factors predictive of exposure, and identify interventions that might
      reduce the frequency of exposure. DESIGN: An analytic, cross-sectional survey.
      STUDY POPULATION: A total of 601 nurses from surgical wards, operating rooms, and
      emergency departments. STUDY INSTRUMENT: An anonymous questionnaire developed by
      the authors on the basis of previously published guidelines was distributed
      between January and March 2003. SAMPLING: Random, with 18 hospitals selected from
      2 urban and rural locations. RESULTS: Almost half of respondents reported having
      had at least 1 puncture injury during the preceding year, 1 in 5 had exposure via
      mucous membranes, and more than half had worked at least once with a recent
      abrasion or cut on their hands. The number of injuries was independent of age
      (P=.26), duration of practice (P=.21), and workplace setting (P=.78). The
      percentage of nurses without percutaneous exposure during the preceding year was
      significantly higher in the group that received special HIV/AIDS training than in
      the group that did not (95% confidence interval, 5.8-24.1%; P<.002). The most
      recent exposure was primarily caused by hollow-bore needles, involved the palm
      and fingers II-V, was self-inflicted, took place during an elective procedure,
      and was not reported to the hospital's infection control center by 74% of
      respondents. The most common reason for not reporting the exposure (38% of cases)
      was the conviction that the source patient was not infected. CONCLUSIONS: Because
      of the large number of occupational exposures to blood, especially those due to
      injuries with hollow-bore needles, nurses should adopt more adequate behavioral
      strategies to prevent the transmission of blood-borne pathogens. Policies for
      providing adequate education programs tailored to encourage nurses to report all
      exposures are urgently required.

PMID- 16465635
TI  - Evaluation of a strategy of screening multiple anatomical sites for methicillin
      resistant Staphylococcus aureus at admission to a teaching hospital.
AB  - We compared the sensitivity of screening with nasal culture alone with that of a
      multiple-site screening method for the identification of carriers of methicillin
      resistant Staphylococcus aureus at hospital admission. If nasal cultures alone
      had been used during the 1-year study, 27.0% of carriers of methicillin-resistant
      S. aureus would have been missed, which corresponds to 560 theoretical isolation
      days. If rectal screening had not been used, 431 theoretical isolation days would
      have been missed, and, if axillary screening had not been used, 99 theoretical
      isolation days would have been missed.

PMID- 16465636
TI  - Reduction in incidence of nosocomial methicillin-resistant Staphylococcus aureus
      (MRSA) infection in an intensive care unit: role of treatment with mupirocin
      ointment and chlorhexidine baths for nasal carriers of MRSA.
AB  - After the introduction of routine treatment for every nasal carrier of
      methicillin-resistant Staphylococcus aureus, active follow-up surveillance for
      nosocomial methicillin-resistant S. aureus infection was conducted for 5 years in
      an intensive care unit of a tertiary-care teaching hospital. There was a
      significant decrease in the incidence of nosocomial methicillin-resistant S.
      aureus infection during the later years of follow-up. Decolonization of nasal
      carriers of methicillin-resistant S. aureus is probably associated with such
      findings.

PMID- 16465638
TI  - The role of gowns in preventing nosocomial transmission of methicillin-resistant
      Staphylococcus aureus (MRSA): gown use in MRSA control.
AB  - During a 2-year period, a standard isolation protocol for control of methicillin
      resistant Staphylococcus aureus was compared with a similar protocol in which
      gowns were not used but the availability of alcohol-based hand disinfectant was
      increased. Intervention wards had 0.10 fewer new MRSA transmissions per ward per
      month, compared with control wards (P was not significant).

PMID- 16465637
TI  - Biofilm formation by and accessory gene regulator typing of methicillin-resistant
      Staphylococcus aureus strains recovered from patients with nosocomial infections.
AB  - The association between biofilm formation and the accessory gene regulator (agr)
      types of methicillin-resistant Staphylococcus aureus (MRSA) strains in our
      hospital were investigated. The biofilm index and the incidence of MRSA strains
      carrying agr-2 in the infection group (n=91) were significantly higher than were
      those in the carrier group (n=225), suggesting that biofilm formation and agr
      type are associated with nosocomial MRSA infections.

PMID- 16465639
TI  - Chest tube-related empyema due to methicillin-resistant Staphylococcus aureus:
      could the chest tube be coated with antiseptics?
AB  - We reviewed the epidemiology, clinical manifestations, and outcomes of 3 cases of
      chest tube-related empyema due to methicillin-resistant Staphylococcus aureus
      (MRSA). Antiseptic-impregnated chest tubes were inserted in cultures containing
      MRSA isolates from these 3 patients, and zone of inhibition were measured. Chest
      tube-related MRSA empyema might complicate tube thoracostomy, and coating the
      chest tube with antiseptic agents could prevent this complication.

PMID- 16465640
TI  - Oxacillin-resistant and multidrug-resistant Staphylococcus aureus in Lima, Peru.
AB  - In a hospital in Lima, Peru, a review of 103 Staphylococcus aureus infections was
      conducted during 2002. The prevalence of oxacillin-resistant S. aureus strains
      was 68%; 25% of strains were resistant to multiple drugs. Previous use of
      antibiotics and undergoing a surgical procedure during the current hospital stay
      were associated with the presence of an oxacillin-resistant S. aureus strain.

PMID- 16465641
TI  - Epidemiological analysis of methicillin-resistant Staphylococcus aureus isolates
      from adult patients with cystic fibrosis.
AB  - Using pulsed-field gel electrophoresis, we genotyped 21 methicillin-resistant
      Staphylococcus aureus isolates from patients attending an adult cystic fibrosis
      unit. Eleven patients exhibited pulsotypes related to 2 locally endemic strains.
      Eleven chronically colonized patients were assessed over a period of up to 2
      years, and all demonstrated a retention of strain type.

PMID- 16465642
TI  - Methicillin-resistant Staphylococcus aureus in Canadian aboriginal people.
AB  - We describe 279 hospitalized Canadian aboriginals in whom methicillin-resistant
      Staphylococcus aureus (MRSA) was detected. They were identified in 38 Canadian
      hospitals from 1995 through 2002. Compared with nonaboriginals, aboriginals were
      more likely to be younger than 18 years of age (OR, 1.8; P<.0001), to have had an
      MRSA infection (OR, 3.8; P<.0001), and to have had MRSA isolated from specimens
      of skin or soft tissue (OR, 4.1; P=.016). The clinical features of MRSA infection
      in aboriginals are distinct from those in the general patient population with
      MRSA infection in Canadian hospitals, and the genetic background of MRSA isolates
      from aboriginals also varies from that of strains from the non-aboriginal
      population.

PMID- 16465643
TI  - Prevalence of and risk factors for carriage of Panton-Valentine leukocidin
      positive methicillin-resistant Staphylococcus aureus among residents and staff of
      a German nursing home.
AB  - The aims of this cross-sectional study were to determine the prevalence of and
      risk factors for carriage of Panton-Valentine leukocidin-producing methicillin
      resistant Staphylococcus aureus (PVL-MRSA) in residents and personnel of a
      nursing home in Germany. In this study, PVL-MRSA carriage status among nursing
      home residents was associated with risk factors reflecting their dependence on
      nursing care. No specific risk factors were detected among staff.

PMID- 16465644
TI  - Molecular epidemiology of Staphylococcus aureus colonization in 2 long-term care
      facilities.
AB  - Persistent colonization with Staphylococcus aureus was assessed in 22 nursing
      home residents. Eighteen residents (82%) remained colonized with the same strain
      found at baseline; 6 (33%) of 18 residents transiently acquired a new strain.
      Four residents (18%) acquired a new persistent strain. Residents colonized with
      methicillin-resistant S. aureus were more likely to acquire a new strain (67%)
      than were residents colonized with methicillin-susceptible S. aureus (20%)
      (P=.04).

PMID- 16465645
TI  - Posttraumatic stress disorder after occupational HIV exposure: two cases and a
      literature review.
AB  - Two healthcare workers developed disabling chronic posttraumatic stress disorder
      after needlestick exposures to blood from a patient infected with human
      immunodeficiency virus (HIV), even though both continue to test negative for HIV
      antibody more than 22 months after their exposures. We describe these 2 cases and
      review the relevant literature. Prospective studies of psychological morbidity
      after occupational needlestick injuries are required to determine the role of
      long-term psychological follow-up, counseling, and support.

PMID- 16465646
TI  - When is a patient with rheumatoid arthritis at risk for cardiovascular disease?

PMID- 16465647
TI  - Screening for pulmonary hypertension in scleroderma: how and when to look?

PMID- 16465648
TI  - Marine oils for antiinflammatory effect -- time to take stock.

PMID- 16465649
TI  - Psoriasis, psoriatic arthritis, or psoriatic disease?

PMID- 16465650
TI  - Magnetic resonance imaging quantification of hand synovitis in patients with
      rheumatoid arthritis treated with adalimumab.
AB  - OBJECTIVE: To investigate the clinical response and to evaluate by magnetic
      resonance imaging (MRI) the inflammatory tissue changes in patients with
      refractory rheumatoid arthritis (RA) treated with adalimumab. METHODS: Thirteen
      patients with refractory RA who were treated with adalimumab (40 mg every 2 weeks
      subcutaneously) were examined with MRI of the dominant affected wrist and hand
      before treatment and one year after therapy. The volume of the enhanced
      inflammatory tissue (VEIT) was evaluated in fat-suppressed contrast-enhanced T1
      weighted MRI images using the Analyse 4.0 software. Disease activity was
      evaluated using the Disease Activity Score 28-joint (DAS-28). Clinical
      improvement was evaluated according to the American College of Rheumatology 20%
      response criteria (ACR20%). RESULTS: We studied 12 women and one man, with mean
      age 52.0 +/- 10.9 years and mean disease duration 13.0 +/- 8.5 years. Eight
      patients had positive IgM rheumatoid factor. One year after treatment, 11 (84.6%)
      patients showed a decrease of the VEIT. Moreover the values of C-reactive protein
      (CRP; 4.3 +/- 6.6 mg/l), the erythrocyte sedimentation rate (ESR; 26.3 +/- 19.5
      mm/h), the DAS-28 (3.5 +/- 1.1), and the VEIT (21.6 +/- 10.7 cm3) after treatment
      were significantly lower compared to the corresponding values before treatment
      (CRP 41.6 +/- 39.2), (ESR 54.3 +/- 28.6) (DAS-28 5.8 +/- 0.8), and (VEIT 36.9 +/-
      16.8) (p < 0.01). All but 3 (76.9%) patients with RA achieved the ACR20%
      response, while 7 (53.8%) and 5 (38.5%) patients achieved ACR50% and ACR70%
      response, respectively. A positive correlation between VEIT, swollen joint count,
      and ESR was found before treatment (r = 0.59, r = 0.64, respectively; p < 0.05).
      CONCLUSION: In patients with refractory RA, treatment with adalimumab resulted in
      improvement of clinical, laboratory, and MRI findings. MRI assessment of the VEIT
      may represent an additional tool for investigation of joint disease activity and
      responsiveness to treatment.

PMID- 16465652
TI  - Course of patient-reported health outcomes in rheumatoid arthritis: comparison of
      longitudinal and cross-sectional approaches.
AB  - OBJECTIVE: To describe health outcomes reported by patients with rheumatoid
      arthritis (RA), i.e., pain, disability and health-related quality of life, as a
      function of disease duration in a longitudinal approach, and to compare the
      course of patient-reported health outcomes by a longitudinal versus a cross
      sectional approach. METHODS: Data were collected with 4 series of questionnaires
      between 1997 and 2002 among patients with RA (maximum number = 882) of varying
      disease duration. The course of patient-reported health outcomes as a function of
      disease duration was evaluated using both longitudinal data and cross-sectional
      data of the first series. RESULTS: The course of RA shows a different pattern for
      various health outcomes. We observed similar trends in health outcomes in this
      large patient sample using the longitudinal and the cross-sectional approach.
      CONCLUSION: Although longterm consequences of RA are preferably assessed in
      longer duration followup studies, cross-sectional studies, including patients
      with a broad range of disease durations, seem to provide fairly reliable
      estimates of the course of health outcomes.

PMID- 16465651
TI  - Single-blind randomized trial of combination antibiotic therapy in rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine the potential clinical efficacy of combination antibiotic
      therapy in treating rheumatoid arthritis (RA). METHODS: Twenty-one patients with
      active RA despite second-line treatment were randomized to receive either
      combination antibiotic therapy (treatment group, n = 11) or no additional therapy
      (control group, n = 10). Antibiotic therapy was given for 12 months and comprised
      oral tetracycline 250 mg twice daily, 3 times per week, and intravenous
      clindamycin infused on 5 consecutive days (300, 300, 600, 600, and 900 mg)
      followed by weekly infusions of 900 mg for 3 weeks and then fortnightly infusions
      for the remainder of the 12 months. The primary outcome measure was the American
      College of Rheumatology 20% (ACR20) response at the end of the initial treatment
      period of 12 months. RESULTS: Five patients in the treatment group (45%) achieved
      an ACR20 response at 1 year compared to none in the control group (p = 0.04).
      Eight patients in the treatment group and 1 in the control group had a greater
      than 20% improvement in tender joint count (p = 0.008). There were also
      significant differences between the groups in physician and patient global
      assessments. Nine patients in the treatment group completed the 6 months'
      followup; of these, 3 sustained the ACR20 response. CONCLUSION: Combined
      antibiotic therapy with intravenous clindamycin and oral tetracycline may be
      useful in the management of active RA. A double-blind, placebo-controlled trial
      of therapy is justified.

PMID- 16465653
TI  - Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate safety and efficacy of etanercept treatment in elderly
      (age > or = 65 yrs) and younger adult subjects (age < 65 yrs) with rheumatoid
      arthritis (RA). METHODS: Subset analyses were used to describe the safety and
      efficacy of etanercept in elderly and younger subjects treated for early and
      disease modifying antirheumatic drug-resistant or late-stage RA (ERA and LRA) in
      one of 4 randomized controlled clinical studies (N = 1353) or 2 longterm
      extensions (N = 1049). RESULTS: Rates of serious adverse events tended to be
      higher in elderly than younger subjects; however, rates of safety events observed
      in elderly etanercept-treated subjects did not exceed rates in elderly placebo or
      methotrexate (MTX)-treated subjects. With regard to efficacy measures [American
      College of Rheumatology 20% response (ACR20), ACR50, and ACR70], elderly subjects
      tended to have somewhat less robust responses to treatment than younger subjects.
      However, for both age groups, treatment with etanercept resulted in improved
      efficacy and function compared with control treatment, and combination therapy
      with etanercept plus MTX resulted in greater efficacy than either etanercept or
      MTX used alone. Efficacy responses of elderly subjects were sustained for up to 6
      years. Radiographic progression (measured using modified Sharp Score) after one
      year of treatment was lower in subjects treated with both etanercept and MTX
      compared with subjects treated with either agent used alone, and this pattern was
      similar in both age groups. CONCLUSION: Consistent with responses in younger
      subjects, elderly subjects with RA treated with etanercept experienced
      significant improvement in disease activity and function without incurring
      additional safety concerns.

PMID- 16465654
TI  - Subclinical atherosclerosis in rheumatoid arthritis in India.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) have high cardiovascular
      morbidity and mortality as compared to the general population. Indians are also
      at increased risk of developing early and severe atherosclerotic coronary artery
      disease. Carotid intima-media thickness as measured by ultrasound is a validated
      surrogate marker of atherosclerosis. We studied the prevalence of subclinical
      atherosclerosis in Indian patients with RA. METHODS: Common carotid IMT (CCA IMT)
      was measured at the level of carotid bifurcation along with fasting lipid profile
      in 57 RA patients and 45 age and sex matched controls. Values of mean CCA IMT
      above mean + 2 SD of the control group were defined as abnormal IMT. Variables of
      disease activity and severity were measured in RA patients. Patients and controls
      with known traditional cardiovascular risk factors were excluded from the study.
      Student t test and chi-square test for proportion were used for statistical
      analysis. A logistic regression analysis was done to find out independent
      predictors of abnormal IMT. RESULTS: Nineteen RA patients (33.3%) and 2 controls
      (4.44%) had abnormal IMT values. RA patients had significantly increased mean CCA
      IMT (0.558 +/- 0.137 mm) as compared to controls (0.416 +/- 0.002 mm; p <
      0.0001). Age > or = 42 years, duration of disease > or= 6 years, and tender joint
      count > or = 5 predicted increased risk of having abnormal CCA IMT in a logistic
      regression analysis. CONCLUSION: One-third of Indian RA patients had subclinical
      atherosclerosis. Age and tender joint count were independent predictors of
      abnormal CCA IMT.

PMID- 16465655
TI  - Revalidation of the original Cedars-Sinai health-related quality of life in
      rheumatoid arthritis questionnaire.
AB  - OBJECTIVE: To assess the psychometric characteristics of the original 33-item
      Cedars-Sinai Health-Related Quality of Life in Rheumatoid Arthritis Questionnaire
      (O-CSHQ-RA) and 11-item CSHQ-RA Short Form (SF) using a representative population
      of patients with rheumatoid arthritis (RA) from 55 sites across the United
      States. METHODS: Data were from a 24-week multicenter, open-label, single-arm
      study of 312 RA patients receiving anakinra. Cronbach's alpha coefficient was
      used to indicate the internal consistency. Test-retest reliability was assessed
      by establishing the intraclass correlation coefficient (ICC) for screening and
      baseline visit responses. Convergent validity was tested with the Pearson
      correlation coefficient. Analysis of variance was performed to determine
      discriminant validity. A Wilcoxon signed-rank test and analysis of covariance
      were used to assess the responsiveness. A discriminant function was generated to
      determine the clinically meaningful change. RESULTS: Test-retest reliability was
      demonstrated for both versions of the CSHQ-RA, with ICC ranging from 0.82 to
      0.94. Cronbach's alpha coefficients were > or = 0.9, indicating good internal
      consistency. Pearson correlations between health-related quality of life
      instruments and CSHQ-RA measures ranged from -0.33 to -0.73 and 0.39 to 0.76,
      demonstrating good convergent validity. Scores on both versions of the CSHQ-RA
      differed significantly (p < 0.0001) for patients with different levels of
      physical disability as measured by the Stanford Health Assessment Questionnaire.
      Both instruments were responsive to differences in patient health as measured by
      the general health question (p < 0.0001). Clinically meaningful changes were
      calculated for all 5 domains of the O-CSHQ-RA (6.9-14.0) and the overall O-CSHQ
      RA SF (12.7). CONCLUSION: These results support the validity and reliability of
      both the original CSHQ-RA and the 11-item CSHQ-RA SF when tested in a
      representative patient population.

PMID- 16465656
TI  - Racial variation in clinical and immunological manifestations of systemic
      sclerosis.
AB  - OBJECTIVE: To clarify which racial differences in disease manifestations can be
      attributed to differences in other factors such as gender, education, disease
      classification, and disease duration. METHODS: The study included white and black
      patients with systemic sclerosis (SSc) treated at a university hospital
      rheumatology clinic between November 1997 and April 2003. Demographic, clinical,
      and immunological measurements were obtained on each subject. Using multivariable
      statistical techniques we assessed differences in disease manifestations between
      white and black patients after adjusting for gender and classification and
      duration of disease. RESULTS: Two hundred sixty-three patients (199 whites, 64
      blacks) were enrolled in the study. Blacks experienced an earlier age at disease
      onset than whites and were significantly more likely to have diffuse disease,
      digital ulcers, digital pitting, impaired lung function, and anti-RNP, and anti
      Ro antibodies. Whites were significantly more likely to have anti-centromere
      antibodies. CONCLUSION: After adjusting for gender, disease classification, and
      disease duration, whites and blacks with SSc differ in some clinical and
      immunological manifestations of disease. Whether these differences can be
      attributed to genetic or environmental factors remains unknown.

PMID- 16465657
TI  - Natural history of mild-moderate pulmonary hypertension and the risk factors for
      severe pulmonary hypertension in scleroderma.
AB  - OBJECTIVE: To determine risk factors for developing pulmonary hypertension (PH)
      in patients with scleroderma (SSc, systemic sclerosis). METHODS: We used a cohort
      of 1136 SSc patients using severe PH as the primary outcome in a natural history
      study. RESULTS: Among 361 individuals with no initial echocardiographic PH, 92
      (26.0%) developed mild-moderate PH and 48 (13.6%) severe PH. Patients developing
      severe PH had lower initial DLCO (48.8% of predicted) than those who did not
      develop PH (56.8% of predicted). Patients with mild-moderate PH had a 17%
      probability of progressing to severe PH, and 15.6% probability of regressing to
      no PH. Individuals with limited disease, mild-moderate PH, and age > or= 47 years
      at diagnosis had a 27.3% probability of developing severe PH, compared to 8.5% in
      individuals with diffuse disease, no evidence of PH, and age < 47 years at
      diagnosis. Longitudinal regression models estimated that individuals with limited
      disease, mild-moderate PH, and DLCO < 50% predicted had an age-adjusted odds
      ratio of 8.6 of developing severe PH within 2 years compared to individuals
      without these risk factors. CONCLUSION: Development of severe PH is uncommon in
      certain subgroups of SSc patients. Risk factors for progression of PH include
      older age, limited skin disease, and elevated pulmonary artery pressures at the
      time of initial evaluation.

PMID- 16465658
TI  - Longitudinal analysis of serum cytokine concentrations in systemic sclerosis:
      association of interleukin 12 elevation with spontaneous regression of skin
      sclerosis.
AB  - OBJECTIVE: Skin sclerosis that progresses in the earlier disease phase in
      systemic sclerosis (SSc) spontaneously regresses thereafter. We investigated the
      relationship between changes of the serum cytokine profile and changes in skin
      fibrosis in patients with SSc. METHODS: Serum cytokine levels were examined by
      ELISA using 180 sera samples from 26 patients with early diffuse cutaneous SSc
      (dcSSc) with mean disease duration of 2.1 years. The mean followup period was 4.9
      years (range 2-8). Cytokine mRNA expression in the affected skin was quantified
      by real-time reverse transcription-polymerase chain reaction. RESULTS: Modified
      Rodnan total skin thickness score decreased after 2, 4, and 6 years compared to
      that at first visit. Serum levels of the Th2 cytokines interleukin 6 (IL-6) and
      IL-10 and monocyte chemotactic protein-1 (MCP-1) were higher at first evaluation
      compared to healthy controls, while IL-4 levels were normal. Levels of all Th2
      cytokines generally decreased as skin sclerosis regressed. Conversely, levels of
      serum IL-12, a Th1-inducing cytokine, were lower at first visit relative to
      controls, but increased by roughly 15-fold after 6 years to significantly higher
      levels than controls. Surviving dcSSc patients exhibited elevated IL-12 levels
      compared to deceased patients. Serum levels of transforming growth factor-ss1
      (TGF-ss1), a fibrogenic cytokine, increased throughout followup, with slightly
      decreased levels at later timepoints. IL-12 mRNA expression was upregulated in
      affected skin from patients with late-stage dcSSc, while TGF-ss1 and MCP-1
      expression was downregulated. CONCLUSION: These results suggest that a shift from
      Th2 to Th1 response correlates with improvement in skin fibrosis in SSc, and that
      IL-12 level is a serologically useful marker for disease activity and prognosis.

PMID- 16465659
TI  - Lack of association of a functional -94ins/delATTG NFKB1 promoter polymorphism
      with susceptibility and clinical expression of biopsy-proven giant cell arteritis
      in northwest Spain.
AB  - OBJECTIVE: Giant cell arteritis (GCA) is a vasculitis preferentially involving
      large and middle-sized arteries in the elderly. The nuclear factor of k-light
      polypeptide gene enhancer in B cells (NF-kB) is a family of 5 proteins expressed
      in most cells that function to regulate gene transcription. NFKB1 gene plays a
      critical role in the coordination of the immune system by regulating the
      transcription of a broad variety of genes implicated in the immune response. A
      NFKB1 promoter polymorphism consisting of a common insertion/deletion (
      94ins/delATTG) located between 2 putative key promoter regulatory elements and
      showing functional effects on the transcription of the NFKB1 gene has been
      described. Since GCA is a polygenic disease, we sought to assess the potential
      role of the -94ins/delATTG NFKB1 promoter polymorphism in susceptibility to GCA
      and to determine if this polymorphism is implicated in the clinical expression of
      this vasculitis. METHODS: Ninety-six patients with biopsy-proven GCA and 204
      ethnically matched Caucasian controls from the Lugo region (Northwest Spain) were
      studied. Genotyping of the -94ins/delATTG NFKB1 promoter polymorphism was
      performed by fluorescent polymerase chain reaction (PCR). RESULTS: No significant
      differences in allele or genotype frequencies for this NFKB1 promoter
      polymorphism were observed between patients with GCA and controls even when
      patients were stratified according to gender, presence of polymyalgia rheumatica
      (n = 38), severe ischemic manifestations (n = 49), or other clinical
      manifestations of GCA. CONCLUSION: Our results do not support a role for 
      94ins/delATTG NFKB1 promoter polymorphism in susceptibility and clinical
      expression of GCA in a Northwestern Spanish population.

PMID- 16465660
TI  - Costs and quality of life of patients with ankylosing spondylitis in Canada.
AB  - OBJECTIVE: The use of biological agents in the treatment of ankylosing
      spondylitis (AS) has emphasized the need for information about the current burden
      of the disease to estimate the cost-effectiveness of these drugs. We investigated
      resource utilization and utility of patients with AS in Canada. METHODS: A cross
      sectional retrospective observational study was performed in a cohort of 545
      patients with AS in Alberta, Ontario, British Columbia, and Manitoba. Patients
      completed a questionnaire asking about their healthcare consumption, out of
      pocket expenses, work capacity, and need for informal care during the past 3
      months. Patients' current functional status and disease activity level was
      assessed using the Bath AS functional and disease activity indexes (BASFI and
      BASDAI), and utility was determined using the EQ-5D 5-dimensional health status
      classification. Descriptive analysis was performed to estimate costs and utility
      for the sample and by level of disease severity. RESULTS: Patients' mean age was
      49.6 years and the mean disease duration was 22.3 years; 64% were male, and 63%
      of patients in the sample were working. The mean BASDAI score was 4.3 and BASFI
      3.6, although 13% of patients in the sample had a BASFI score > or = 7. The mean
      annual cost per patient is estimated at 9,008 Canadian dollars (SD 17,724
      Canadian dollars), and direct healthcare represented 28.9% of these costs.
      Patients' out of pocket costs represented 33.1%, and lost work capacity accounted
      for 38%. Costs increased significantly with diminishing physical function and
      high disease activity, covering a range of 4,000 Canadian dollars to 30,000
      Canadian dollars per patient and year. The estimated cost-increase per unit
      increase in the BASFI score at values < 5 was around 1,000 Canadian dollars, and
      more than 5,000 Canadian dollars at values > 7. The mean utility was 0.65 (SD
      0.23). Utility was significantly correlated with age, sex, BASFI, and BASDAI,
      covering a range from 0.87 for patients with BASFI/BASDAI < or = 2 to 0.20 for
      patients with BASFI/BASDAI > or = 8. On average, utility decreased by 0.075 for
      each unit-increase in the BASFI. CONCLUSION: All types of costs accelerate
      steeply with increasing loss of function (BASFI) and disease activity (BASDAI) in
      patients with AS, while utility decreases significantly. Treatments that control
      disease activity and maintain patients' function are likely to offset the high
      cost and low quality of life of severe disease. Our findings provide information
      on the burden of AS and a baseline for assessing the cost-effectiveness of the
      new biological agents in this indication.

PMID- 16465661
TI  - Muscarinic acetylcholine type-3 receptor desensitization due to chronic exposure
      to Sjogren's syndrome-associated autoantibodies.
AB  - OBJECTIVE: Anti-muscarinic acetylcholine type-3 receptor (anti-M3R)
      autoantibodies have been shown to inhibit M3R-mediated responses by both in vitro
      contractility and fura-2 microfluorimetry analyses of intracellular calcium
      mobilization, suggesting an important role for anti-M3R autoantibody in secretory
      dysfunction. We investigated whether chronic stimulation of M3R by anti-M3R
      autoantibodies and/or the agonist pilocarpine results in a general M3R
      desensitization. METHODS: Carbachol-evoked responses of mouse-bladder smooth
      muscle strips were measured following exposure to anti-M3R-positive and/or anti
      M3R-negative sera from either NOD/Lt mice, a model of SS-like disease, or human
      patients with primary SS. RESULTS: Bladder smooth muscle strips isolated from
      NOD/Lt mice with circulating anti-M3R autoantibodies exhibited lower carbachol
      evoked responses than smooth muscle strips from anti-M3R autoantibody-negative
      NOD/Lt mice and control C57BL/6 mice. Repeated pilocarpine injections of NOD mice
      for 6 days also revealed M3R desensitization in the agonist-evoked contractile
      assay, whereas age and sex matched C57BL/6 mice injected with pilocarpine for the
      same period showed a 2-fold higher response. Incubation of smooth muscle strips
      with sera obtained from patients with primary SS resulted in both stimulated and
      inhibited responses. CONCLUSION: These results support the hypothesis that
      chronic stimulation of membrane-bound M3R can result in receptor desensitization,
      and raise questions about repeated use of pilocarpine by patients positive for
      anti-M3R autoantibodies.

PMID- 16465662
TI  - Subjective improvement in patients with psoriatic arthritis after short-term oral
      treatment with seal oil. A pilot study with double blind comparison to soy oil.
AB  - OBJECTIVE: To investigate effects of short-term oral treatment with seal oil in
      patients with psoriatic arthritis (PsA). METHODS: Forty-three patients with
      polyarticular PsA were randomized to receive oral treatment for 2 weeks with
      either seal oil or soy oil in a double blind controlled trial. Clinical and
      biochemical variables were assessed at baseline, after treatment, and 4 weeks
      post-treatment. Patients were allowed to continue nonsteroidal antiinflammatory
      drugs (NSAID) and disease modifying antirheumatic drugs (DMARD) during the study.
      RESULTS: Forty patients completed the study, 20 in each treatment group. Patients
      in the seal oil group reported a significant improvement in global assessment of
      the disease 4 weeks post- treatment (p < 0.01), and both groups showed a trend
      toward improvement in tender joint count, but the differences between the groups
      were not significant. There was a fall in the ratio of n-6 to n-3 fatty acids and
      in arachidonic acid (AA) to eicosapentaenoic acid (EPA) in serum after treatment
      with seal oil (p < 0.01). Twenty-one percent of all patients had elevated values
      of calprotectin in feces suggestive of asymptomatic colitis. CONCLUSION:
      Treatment with seal oil was followed by a modest improvement in patient's global
      assessment of the disease and a trend towards a decrease in number of tender
      joints. There was a shift in fatty acid composition in serum toward a putative
      antiinflammatory profile. Oral treatment with seal oil may have NSAID-like
      effects in PsA.

PMID- 16465663
TI  - Urokinase-type plasminogen activator, receptor, and inhibitor correlating with
      gelatinase-B (MMP-9) contribute to inflammation in gouty arthritis of the knee.
AB  - OBJECTIVE: To determine the possible role of the plasminogen activator
      (PA)/plasmin system in gouty arthritis. METHODS: We compared the antigenic values
      of urokinase-type PA (uPA), soluble uPA receptor (suPAR), and PA inhibitor type-1
      (PAI-1) and the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in 63
      synovial fluid (SF) samples from knee joints of 38 patients with gouty arthritis
      and 20 SF samples from knee joints of 20 patients with osteoarthritis (OA).
      RESULTS: The increases of uPA, suPAR, and PAI-1 antigenic values in SF were
      associated with increased levels of latent MMP-9 (pro-MMP-9) (p < 0.001, p <
      0.001, p < 0.001, respectively) in gouty arthritis, whereas a correlation was not
      observed between uPA, suPAR, and PAI-1 antigenic values and MMP-2 levels.
      Increased uPA, suPAR, and PAI-1 antigenic values in gouty arthritis SF were also
      correlated to each other (p < 0.001, p < 0.001, p < 0.001). In gouty arthritis
      SF, no significant relations were observed between uPA and suPAR antigenic values
      and leukocyte, neutrophil, or monocyte counts, while increased values of PAI-1
      corresponded closely with increased leukocyte and neutrophil counts (p = 0.005, p
      = 0.004). Significantly higher values of the uPA, suPAR, and PAI-1 (p < 0.001, p
      < 0.001, p = 0.012) appeared in SF of gouty arthritis than in SF from patients
      with OA. CONCLUSION: These results show a correlation of the PA/plasmin system
      and MMP-9 in SF from patients with gouty arthritis, resulting in increased PA
      catalytic activity and contributing to inflammation in gouty arthritis.

PMID- 16465664
TI  - The serine protease inhibitor trappin-2 is present in cartilage and synovial
      fluid in osteoarthritis.
AB  - OBJECTIVE: Trappins are small serine protease inhibitors bound to extracellular
      matrix (ECM) through the actions of transglutaminase (TGase) enzymes. Trappin-2
      is present in many tissues and is upregulated at sites of injury. In
      osteoarthritis (OA), serine proteases contribute to articular cartilage
      destruction, and TGase activity is increased. Yet little is known about matrix
      bound serine protease inhibitors or TGase substrates in articular cartilage. Our
      purpose was to determine if trappin-2 was present in OA cartilage and synovial
      fluid (SF). METHODS: OA knee articular cartilage and SF were assayed for trappin
      2 protein by Western blotting, ELISA, and immunohistochemistry. Trappin-2 mRNA
      was detected with RT-PCR. The ECM components bound to trappin-2 were identified
      by 2-D gel electrophoresis and peptide fingerprinting. RESULTS: Trappin-2 was
      detectable in OA articular cartilage extracts, cultured chondrocytes, conditioned
      media, and SF by Western blotting. OA cartilage protein extracts contained
      significantly higher quantities of trappin-2 than normal cartilage protein
      extracts (22.98 +/- 1.28 ng/mg wet weight vs 14.97 +/- 1.92 ng/mg wet weight; p <
      0.01). RT-PCR confirmed the presence of trappin-2 mRNA in OA chondrocytes.
      Immunohistochemical studies of OA cartilage revealed trappin-2 protein in
      chondrocytes. Peptide mapping of trappin-2 binding partners showed that
      fibromodulin was bound to trappin-2 in cartilage. CONCLUSION: We confirmed the
      presence of trappin-2 in OA cartilage and SF. Elevated levels of TGase activity
      in OA cartilage may increase levels of this serine protease inhibitor in response
      to injury.

PMID- 16465665
TI  - Does the nature of deposited basic calcium phosphate crystals determine clinical
      course in calcific periarthritis of the shoulder?
AB  - OBJECTIVE: Two typical clinical courses of calcific periarthritis in the shoulder
      are known: acute, with severe inflammation, and chronic, in the form of
      impingement syndrome with secondary subacromial bursitis. It remains unclear what
      factors determine these clinical courses. Our objectives were to clarify whether
      the calcified deposits that occur in both acute and chronic cases are composed of
      carbonate apatite; and to compare the Ca:P molar ratio in the 2 forms and to
      determine if there was any correlation in this respect with the intensity of
      inflammation induced by basic calcium phosphate crystals. METHODS: Ten samples
      were aspirated from 10 women (ages 42-65 yrs) with acute inflammation. The
      average time from first attack to aspiration was 2.3 days. A further 10 samples
      were operatively removed from 10 women (ages 35-58 yrs) with refractory chronic
      subacromial bursitis, among whom an average of 7.8 months had passed since the
      onset of symptoms. All samples were analyzed by x-ray diffraction, Fourier
      transform infrared spectroscopy, and Raman spectroscopy, and Ca:P molar ratios
      were measured by x-ray fluorescence spectrometry. RESULTS: Calcified deposits
      from both acute and chronic cases were identified as carbonate apatite, and not
      hydroxyapatite, octacalcium phosphate, tricalcium phosphate, or dicalcium
      phosphate dihydrate. The average Ca:P molar ratio of calcified deposits was
      calculated as 1.71 +/- 0.16 in acute cases and 1.71 +/- 0.16 in chronic cases
      (statistically nonsignificant). CONCLUSION: Deposits around the shoulder in both
      acute and chronic calcific periarthritis are composed of carbonate apatite, Ca:P
      molar ratios being almost identical in the 2 forms. The results suggest that some
      factor other than the composition of the crystalline deposits may determine
      clinical course in calcific periarthritis of the shoulder.

PMID- 16465666
TI  - Adherence during an individualized home based 12-week exercise program in women
      with fibromyalgia.
AB  - OBJECTIVE: Treatment recommendations for fibromyalgia (FM) include regular
      physical exercise. In this prospective study we examined predictors for adherence
      to stretching and aerobic exercises in women provided with an individualized home
      based program. METHODS: Thirty-nine women kept exercise diaries for 12 weeks.
      RESULTS: For both types of exercise, women who were less physically fit at
      baseline engaged in more exercise during the program. Yet for stretching, more
      lower body pain at baseline predicted engaging in less stretching exercise over
      time, whereas for aerobic exercise, more baseline upper body pain predicted more
      exercise over time. As time passed, participants with higher baseline physical
      fitness and/or older age were reducing their aerobic exercise practice at
      significantly faster rates, as were those women with higher baseline stress.
      CONCLUSION: Given that adequate levels of adherence were limited to about half of
      the participants for both types of exercise, steps to reduce barriers to exercise
      (e.g., stress) need to be taken when prescribing exercise in the treatment of FM.

PMID- 16465667
TI  - Health status indicators among community-dwelling elders with arthritis: the
      Bambui health and aging study.
AB  - OBJECTIVE: To investigate the association of arthritis with health status
      indicators among elders living in Bambui, Brazil. METHODS: A cross-sectional
      study was conducted among 1606 elders using baseline data from the Bambui Health
      and Aging Study, a population based cohort study of older adults. Arthritis was
      self-reported and defined as a physician diagnosis of arthritis or rheumatism,
      and/or chronic hand and knee symptoms. Health status indicators, defined a priori
      as the main independent variables, were self-rated health, psychological distress
      (based on the General Health Questionnaire), report of sleep complaints,
      disability in activities of daily living (ADL), "2-week" disability, mobility
      disability, and 2 composite indexes of mental health problems and physical
      disability problems. Logistic regression compared health status indicators among
      elders reporting arthritis (N = 833) and non-arthritis subjects. RESULTS: After
      controlling for sociodemographics and chronic conditions, all measures were found
      to be associated with arthritis: sleep complaints (OR 1.81, 95% CI 1.43-1.92),
      fair (OR 2.17, 95% CI 1.62-2.90) and poor self-rated health (OR 3.48, 95% CI 2.46
      4.94), ADL disability (OR 1.73, 95% CI 1.02-2.87), mobility disability (OR 2.65,
      95% CI 2.06-3.41), 2-week disability (OR 1.86, 95% CI 1.35-2.57), 2 mental health
      problems (OR 2.25, 95% CI 1.67-3.04), and one (OR 2.46, 95% CI 1.91-3.16) and 2
      physical disability problems (OR 4.19, 95% CI 2.02-8.59). CONCLUSION: Considering
      the paucity of similar studies addressing the impact of arthritis in developing
      nations, these findings may be applied to similar communities and support better
      planning of resource allocations to minimize the effects of arthritis among the
      elderly.

PMID- 16465668
TI  - Arthritis prevalence and symptoms among US non-veterans, veterans, and veterans
      receiving Department of Veterans Affairs Healthcare.
AB  - OBJECTIVE: . Studies suggest arthritis and rheumatic diseases are common among
      military veterans, but prior research has not directly compared arthritis between
      veterans and the general population. This study compared arthritis prevalence and
      symptoms between veterans of the US Armed Forces and non-veterans, and between
      veterans who are US Department of Veterans Affairs (VA) healthcare users and
      veteran nonusers. METHODS: Study participants were 123,395 respondents from 36
      states that completed the 2000 Behavioral Risk Factor Surveillance System
      arthritis module. Analyses compared self-reports of doctor-diagnosed arthritis,
      chronic joint symptoms, and activity limitation according to veteran status.
      Analyses also compared relationships of demographic characteristics to arthritis
      according to veteran status. RESULTS: US veterans were more likely to report
      doctor-diagnosed arthritis than non-veterans (32% vs 22%; p < 0.001), and VA
      healthcare users were more likely to report doctor-diagnosed arthritis than
      veteran nonusers (43% vs 30%; p < 0.001). Differences remained in analyses
      controlling for demographic characteristics. Among respondents with arthritis,
      veterans were more likely to report chronic joint symptoms and activity
      limitation than non-veterans, and VA healthcare users were more likely to report
      chronic symptoms and activity limitation than veteran nonusers. Demographic
      factors predicting doctor-diagnosed arthritis were similar among the 3 groups.
      CONCLUSION: This study shows a significant burden of arthritis among US veterans,
      particularly VA healthcare users. Increased prevention of orthopedic injuries in
      the military may reduce the risk of arthritis in veterans. Within the VA
      healthcare system, self-management interventions may help to improve outcomes
      among the many patients with arthritis.

PMID- 16465669
TI  - Rituximab treatment for resistant antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) and catastrophic antiphospholipid syndrome (CAPS)
      can be challenging to treat. As they are rare, clinicians are not often exposed
      to these complex diseases. For the patient resistant to standard treatments new
      therapeutic directions can be perplexing, especially in the context of ongoing
      thromboses and bleeding episodes. We describe 3 patients, 2 with APS and one with
      CAPS, resistant to conventional medications, who responded to treatment with
      rituximab, an anti-CD20 monoclonal antibody. Since rituximab infusion, all the
      patients have had stable platelet counts and no further episodes of bleeding or
      thromboses.

PMID- 16465670
TI  - Multifocal idiopathic fibrosclerosis: treatment of 2 cases with cyclosporine.
AB  - We describe 2 cases of multifocal idiopathic fibrosclerosis treated successfully
      with cyclosporine. The first patient presented with chronic abdominal pain and
      was subsequently found to have retroperitoneal fibrosis with ureteral
      obstruction. Other findings included cholangiolar fibrosis, retroorbital
      pseudotumors, submandibular gland enlargement, subcutaneous fibrotic masses, and
      elevated erythrocyte sedimentation rate (ESR) and serum creatinine. He initially
      responded well to temporary ureteral stenting followed by combination therapy
      with steroids and cyclosporine. He relapsed when cyclosporine was stopped, but
      subsequently remitted completely when cyclosporine was reintroduced. The second
      patient presented with long-standing abdominal pain with retroperitoneal
      fibrosis, submandibular gland enlargement, and an enlarged pancreas with a
      localized mass, all of which improved significantly with 6 months of therapy with
      cyclosporine. Cyclosporine was well tolerated with no significant side effects in
      the 2 patients. A review of the literature is presented.

PMID- 16465671
TI  - Development of polymyositis after long-standing rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) and polymyositis (PM) are distinct clinical syndromes.
      The concurrent diagnoses of RA and PM in the same patient are rare. We describe a
      patient who developed outright PM after 16 years of well established RA, review
      the literature, and highlight the need to consider a broad base of differentials
      including PM in the diagnosis of muscle weakness in RA.

PMID- 16465672
TI  - Meningeal involvement in Wegener's granulomatosis.
AB  - We describe a patient with Wegener's granulomatosis (WG) who developed
      neurological symptoms attributed to meningeal involvement. The diagnosis of WG
      was complicated by persistently negative antineutrophil cytoplasmic antibodies
      (ANCA) and lack of specificity in the histopathological findings from multiple
      anatomical sites. This rare neurological manifestation of WG was treated
      successfully with oral cyclophosphamide and the patient has continued remission
      for 3 years taking oral methotrexate.

PMID- 16465673
TI  - Tribute: John Francis Lydiard "Jack" Woodbury.

PMID- 16465674
TI  - Dr. John Woodbury -- a personal recollection.

PMID- 16465676
TI  - Should anti-tumor necrosis factor-alpha be the first therapy for rheumatoid
      vasculitis?

PMID- 16465677
TI  - Definition of clinical differences.

PMID- 16465678
TI  - Antibodies to cyclic citrullinated peptides in psoriatic arthritis: do
      classification criteria affect study results?

PMID- 16465682
TI  - Use of statistical analysis in open extension studies.

PMID- 16465683
TI  - Toll bridge to immunity. Immune molecules hold promise for vaccine adjuvant
      discovery.

PMID- 16465684
TI  - Vaccine research lines converge. Vaccinologists working on different diseases met
      in Germany to exchange ideas--and found that their approaches already have a
      great deal in common.

PMID- 16465685
TI  - HIV prevention in a pill? Can drugs that combat herpes virus help reduce HIV
      transmission?

PMID- 16465686
TI  - An interview with Barton Haynes. A new virtual center. Interview by Simon Noble.

PMID- 16465687
TI  - Renewed promise. Annual AIDS vaccine meeting highlights recent data from clinical
      trials and lessons on recruitment and retention of volunteers.

PMID- 16465688
TI  - Merck's HPV vaccine shines in Phase III trials.

PMID- 16465689
TI  - Clinical trials yield promising results from two adenovirus-based vaccines.

PMID- 16465690
TI  - Fragmentation of sialylated carbohydrates using infrared atmospheric pressure
      MALDI ion trap mass spectrometry from cation-doped liquid matrixes.
AB  - Infrared atmospheric pressure matrix-assisted laser desorption/ionization on an
      ion trap mass spectrometer is used to study sialylated oligosaccharides desorbed
      from the liquid phase. Glycerol doped with various cations provides the
      opportunity to produce cation-adducted intact molecular ions of sugars. Distinct
      combinations of cations allow for sialic acid stabilization, as well as
      differential cleavage, resulting in more complete fragmentation coverage of the
      oligosaccharide. Alkali and transition metal cations are utilized to create three
      distinct molecular ion species, involving the adduction of a singly charged
      cation, two singly charged cations, or a doubly charged cation. From these
      different molecular ion types, complementary sequence, branching, and linkage
      information for sialylated oligosaccharides can be deduced.

PMID- 16465691
TI  - Commentary: the pharmacological antioxidant amifostine -- implications of recent
      research for integrative cancer care.
AB  - Amifostine is a pharmacological antioxidant used as a cytoprotectant in cancer
      chemotherapy and radiotherapy. It is thought to protect normal tissues relative
      to tumor tissue against oxidative damage inflicted by cancer therapies by
      becoming concentrated at higher levels in normal tissues. The degree to which
      amifostine nevertheless accumulates in tumors and protects them against cancer
      therapies has been debated. Guidelines have been published that direct its use in
      chemotherapy and radiation, taking into consideration the concerns of tumor
      protection. In this article, clinical studies of amifostine appearing since the
      publication of the most recent set of guidelines are reviewed. Randomized and
      nonrandomized trials of regimens involving chemo-therapeutic agents
      (chemotherapy, chemoradiation, conditioning regimens for bone marrow transplant)
      are discussed. Nineteen studies showed positive effects for amifostine reducing
      the level of side effects of these regimens, while 9 showed no effect and 1 had a
      questionable result. Clinically relevant levels of amifostine toxicity were
      observed in several studies, but subcutaneous administration may reduce such
      toxicity. Amifostine showed protection against mucositis, esophagitis,
      neuropathy, and other side effects, although protection against cisplatin-induced
      ototoxicity was not observed. No evidence of tumor protection was observed.
      Amifostine may enable populations unable to tolerate conventional cancer therapy
      to receive treatment of their cancers, even if some degree of tumor protection is
      eventually discovered. The authors discuss the implications of this research for
      patient populations seen in integrative cancer care centers and for research on
      phytochemical antioxidants such as vitamins and carotenoids.

PMID- 16465692
TI  - From SCHIP benefit design to individual coverage decisions.
AB  - The majority of states have implemented separate SCHIP (S-SCHIP) programs that
      significantly depart from Medicaid and resemble less comprehensive commercial
      products. This difference in program design may result in S-SCHIP potentially
      being less responsive to children with special needs (CSHCNs). This study
      explores how responsive insurers are to these higher than average needs. We found
      that, with one exception, insurers did not agree on the coverage of any specific
      service, but overall they provided coverage beyond state limits and exclusions.
      Second, the less acute the childhood condition, the more frequently insurers
      imposed exclusions. Finally, in the majority of states, some insurers excluded
      services that arguably should have been covered according to the plan/contract
      language. We conclude that SCHIP coverage at current levels may not be sufficient
      to care for CSHCNs, making external reviews of insurers' coverage decisions and
      coordination with other sources of care important components of SCHIP program
      design.

PMID- 16465693
TI  - Electron ionization for LC/MS.

PMID- 16465694
TI  - Electrospray-mass spectrometric analysis of reference carboxylic acids and
      Athabasca oil sands naphthenic acids.
AB  - Naphthenic acids (NAs) are complex mixtures of naturally occurring acyclic and
      cyclic aliphatic carboxylic acids that are responsible for the toxicity of the
      water in the tailings ponds associated with the recovery of bitumen from the
      Athabasca oil sands. NAs are difficult to analyze due to their complexity and the
      lack of commercially available NA standards. This paper describes the use of
      negative ion electrospray ionization mass spectrometry for the analysis of NAs.
      Model carboxylic acids, alone and in mixture, afforded mass spectral signal
      intensities that were highly dependent on extractor and cone voltages and on
      molecular structure. These effects were also observed for authentic NAs. Under
      conditions that were close to optimal for all the model compounds, their
      calibration sensitivities varied by a factor of <2, and there were minimal
      interactions when the model compounds were examined in mixture. Under the same
      conditions, the authentic NAs showed apparent congener distributions similar to
      those observed previously by GC/MS for derivatized NAs. The similar calibration
      sensitivities among congeners allowed the use of the standard addition method to
      determine the approximate absolute concentrations of NA congeners in an authentic
      sample.

PMID- 16465695
TI  - A capillary mixer with adjustable reaction chamber volume for millisecond time
      resolved studies by electrospray mass spectrometry.
AB  - A novel continuous-flow apparatus for on-line kinetic studies of (bio)chemical
      solution-phase processes by electrospray ionization mass spectrometry (ESI-MS) is
      described. The device is based on two concentric capillaries. Fluid is released
      from the inner capillary into the intercapillary space, where it mixes with
      solution flowing through the outer capillary, thus initiating the reaction of
      interest. Gas-phase analyte ions are formed near the tip of the outer capillary
      by pneumatically assisted ESI. This setup allows the mixer to be placed directly
      within the ion source, thus providing a minimal dead volume of ~8 nL. Time
      resolved data can be recorded in both "spectral" and "kinetic" modes. In the
      former case, the position of the inner capillary is fixed at various points, such
      that entire mass spectra can be recorded for selected reaction times. For
      experiments in kinetic mode, the mass spectrometer monitors the signal intensity
      at selected m/z values, while the inner capillary is continuously pulled back,
      thus providing intensity-time profiles for specific reactive species. A
      theoretical framework is developed that allows the measured kinetics to be
      analyzed by taking into account the effects of laminar flow within the reaction
      capillary. Failure to take these effects into account results in erroneous rate
      constants. Studies on the demetalation kinetics of chlorophyll reveal that the
      apparatus can reliably measure rate constants up to at least 100 s-1. This
      represents a substantial improvement over previous ESI-MS-based kinetic methods.
      Spectral mode experiments on the refolding of ubiquitin show the changing
      proportions of denatured and tightly folded protein subpopulations in solution.
      When monitored in kinetic mode, the refolding process was found to proceed with a
      rate constant of 5.2 s-1.

PMID- 16465696
TI  - Capabilities of laser ablation mass spectrometry in the differentiation of
      natural and artificial opal gemstones.
AB  - The potentialities of laser ablation coupled to ion cyclotron resonance Fourier
      transform mass spectrometry are evaluated to distinguish natural and artificial
      opals. The detection of specific species in both ion detection modes leads us to
      obtain relevant criteria of differentiation. In positive ions, species including
      hafnium and large amounts of zirconium atoms are found to be specific for
      artificial opal. In contrast, aluminum, titanium, iron, and rubidium are
      systematically detected in the study of natural opals. Moreover, some ions allow
      us to distinguish between natural opal from Australia and from Mexico. Australian
      gemstone includes specifically strontium, cesium, and barium. Moreover, it is
      also found that the yield of (H2O)0-1(SiO2)nX- (X- = O-, OH-, KO-, NaO-, SiO2-,
      AlO1-2-, FeO2-, ZrO2-, and ZrO3-) and (Al2O3)(SiO2)nAlO2- ions depends on the
      composition of the sample when opals are laser ablated. Ions, which include
      zirconium oxide species, are characteristics of artificial gem. In contrast,
      natural opals lead us, after laser ablation, to the production of ions including
      H2O, Al2O3 motifs and AlO-, KO-, NaO-, and FeO2- species.

PMID- 16465697
TI  - Turbidimetric detection method in flow-assisted separation of dispersed samples.
AB  - Characterization of dispersed samples is an outstanding trend in analytical
      science. Among flow-assisted separation techniques for dispersed samples, size
      exclusion chromatography, hydrodynamic chromatography, and field-flow
      fractionation are the most widely applied. With dispersed analytes separated by
      these techniques, the UV/vis spectrophotometric detectors work as turbidimeters.
      To directly convert the analytical signal for quantitative analysis, the
      extinction properties of the dispersed analyte must be known. A new method is
      proposed to experimentally obtain-by single-run, flow-assisted separation with
      UV/vis diode-array detectors-the mass-size (or number-size) distribution function
      of the analytes when a retention-to-size relationship is either theoretically or
      empirically available for the chosen separation technique. This approach needs
      neither standards nor reliance on a method to predict the optical properties of
      the analytes. Theory and original algorithms are presented. Algorithms are then
      tested to optimize the numerical routines. Accuracy and robustness of the method
      are evaluated by simulation, and limitations for the application to experimental
      data are described. Finally, first application to field-flow fractionation shows
      validity of the method when applied to a few real cases.

PMID- 16465698
TI  - Can money buy quality? Physician response to pay for performance.
AB  - While pay for performance (P4P) has created a nationwide buzz among health plans,
      physicians and hospitals, most P4P initiatives are still on the drawing board,
      according to findings from the Center for Studying Health System Change's (HSC)
      2005 site visits to 12 nationally representative communities. HSC focused on
      performance-based payment for physicians, finding that only two HSC communities
      Orange County, Calif., and Boston-have significant physician P4P programs. In the
      other 10 communities, where almost no physicians have received quality-related
      payments to date, physician attitudes about P4P ranged from skeptical to hostile.
      P4P, a concept best suited to larger physician groups, may be difficult to
      implement in markets dominated by small physician practices. In spite of
      substantial barriers to initiating performance-related payment for physicians,
      most large health plans and Medicare are planning P4P programs.

PMID- 16465699
TI  - Ion transport diagnostics in a microsecond pulsed Grimm-type glow discharge time
      of-flight mass spectrometer.
AB  - A Grimm-type glow discharge ion source, operated in the microsecond pulsed mode,
      has been interfaced to a commercial time-of-flight mass spectrometer. Ion
      transport from the source to the mass spectrometer, an inherent limitation of a
      Grimm source and mass spectrometer combination, was evaluated. The primary
      discharge operating conditions found to influence transport efficiency were gas
      flow rate and source pressure. The configuration of the Grimm-type source also
      influenced ion transport, including use of a gas-directing sleeve device. The
      effect of transport efficiency was separated into two components: (1) total ion
      signal and (2) temporal resolution. The latter is an advantage afforded by use of
      a pulsed glow discharge source and time-of-flight spectrometer, which allows
      discrimination against interfering gaseous background ions by appropriate ion
      sampling time. Shown as an example is the identification of trace magnesium from
      potential background interference using an optimized source configuration based
      on this temporal resolution method.

PMID- 16465700
TI  - Do specialty hospitals promote price competition?
AB  - Policy makers continue to debate the correct public policy toward physician-owned
      heart, orthopedic and surgical specialty hospitals. Do specialty hospitals offer
      desirable competition for general hospitals and foster improved quality,
      efficiency and service? Or do specialty hospitals add unneeded capacity and
      increased costs while threatening the ability of general hospitals to deliver
      community benefits? In three Center for Studying Health System Change (HSC) sites
      with significant specialty hospital development--Indianapolis, Little Rock and
      Phoenix--recent site visits found that purchasers generally believe specialty
      hospitals are contributing to a medical arms race that is driving up costs
      without demonstrating clear quality advantages.

PMID- 16465701
TI  - Biography of Professor Zhen Yao.

PMID- 16465702
TI  - Prescription drug monitoring programs.

PMID- 16465703
TI  - Calibration for on-site analysis of hydrocarbons in aqueous and gaseous samples
      using solid-phase microextraction.
AB  - Rapid sampling and sample preparation methodology was investigated using
      adsorptive poly(dimethylsiloxane)/divinylbenzene and
      Carboxen/poly(dimethylsiloxane) solid-phase microextraction (SPME) fiber coatings
      and volatile aromatic hydrocarbons (BTEX: benzene, toluene, ethylbenzene, and o
      xylene). A flow-through system was used to generate a standard aqueous solution
      of BTEX as model sample with known linear velocity. Parameters that affect the
      extraction process, including sampling time, concentration, water velocity, and
      temperature, were investigated. Very short sampling times from 10 s and sorbents
      with strong affinity and large capacity were used to ensure the effect of '"zero
      sink" and to calibrate the extraction process in the initial linear extraction
      region. Several different concentrations were investigated, and it was found that
      mass uptake changes with concentration linearly. The increase of water velocity
      increases mass uptake, though the increase is not linear. Temperature does not
      affect mass uptake significantly under typical field sampling conditions. To
      further accurately describe rapid SPME analysis of aqueous samples, a new model
      translated from heat transfer to a circular cylinder in cross-flow was used. An
      empirical correlation to this model was used to predict the mass-transfer
      coefficient. Findings indicate that predicted mass uptake compares well with
      experimental mass uptake. The new model was tested for rapid air sampling, and it
      was found that this new model also predicted rapid air sampling accurately.
      Findings presented in this study extend the existing fundamental knowledge
      related to rapid sampling/sample preparation with SPME.

PMID- 16465704
TI  - Quantitative analysis of synthetic polymers using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Quantitative analyses of synthetic polymers were accomplished using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF
      MS). Many factors have hindered the development of quantitative measurement of
      polymers via MALDI TOF MS, e.g., laser power, matrix, cation salt, and
      cocrystallization. By probing the optimal conditions, two sets of polymers were
      studied. Fair repeatability of the samples ensures acceptable results. In set 1,
      two poly(ethylene glycols) with different end groups showed equal
      desorption/ionization efficiencies. Two synthetic polymers in set 2 with
      different chemical properties resulted in different MALDI responses. Good
      linearity was achieved by plotting the relationship between the sample
      concentration ratio and the total signal intensity ratio in both sets.

PMID- 16465705
TI  - Diffusion of redox probes in hydrated sol-gel-derived glasses. Effect of gel
      structure.
AB  - The diffusion coefficients of redox probes entrapped in a silica matrix prepared
      by the sol-gel process were measured using a combination of cyclic voltammetry
      and chronoamperometry at an ultramicroelectrode. In this study, the porosities of
      the gels were varied to assess the importance of constrained environments vs
      intermolecular interactions on the translational mobility of guests entrapped in
      this solid host matrix. The average pore diameter of the gels was varied from 40
      to 400 A by utilizing different catalysts (HCl, NH3, NaF) or different silicon
      precursors (tetramethoxysilane or Ludox colloidal silica). The diffusion
      coefficients of cobalt(II) tris(bipyridine), ferrocenemethyltrimethylammonium
      ion, and dicyanobis(phenanthroline)iron(II) and their rate of change as the gel
      dried were found to be nearly identical for gels prepared from TMOS and catalyzed
      with either HCl, NH3, or NaF. When trapped in gels prepared from Ludox,
      ferrocenemethanol and potassium ferricyanide diffused at rates identical to that
      measured in solution. In contrast, Dapp for ferrocenemethyl(trimethylammonium)
      dropped 1 order of magnitude over a 30-day drying period. These results attest to
      the importance of intermolecular interactions in governing diffusion in sol-gel
      derived materials.

PMID- 16465706
TI  - Measurement of association and dissociation rate constants for lead(II)/18-crown
      6 using square wave voltammetry at a glassy carbon mercury film electrode.
AB  - Understanding the rate parameters of metal ion-ligand complexes is necessary for
      sensing, separations, and responsive materials. The complexation between 18-crown
      6 and lead(II) is of particular interest due to the potential use of this
      chemistry in sensors and separations. We have applied square wave voltammetry at
      a glassy carbon mercury film electrode to this problem. Lead(II) in aqueous
      solution containing an excess of 18-crown-6, studied with different experimental
      time scales, yields stoichiometry, binding constants, and rate constants (25
      degrees C). For pulse times longer than 10 ms, the glassy carbon mercury film
      electrode acts as a planar electrode. For shorter pulse times, a roughness
      correction factor must be used to calculate dimensionless current because of the
      increase in effective area due to the droplike nature of the adsorbed mercury.
      Lead(II) forms a 1:1 complex with 18-crown-6 in both nitrate and perchlorate
      media. Log K for the complex with the nitrate counterion is 4.13 +/- 0.09 (SEM);
      in the presence of perchlorate it is 4.35 +/- 0.09 (SEM). The formation rate
      constants, kf, for the nitrate and perchlorate systems are (3.82 +/- 0.89) x 107
      and (5.92 +/- 1.97) x 106 M-1 s-1, respectively. The dissociation rate constants,
      kd, are (2.83 +/- 0.66) x 103 s-1 with nitrate as the counterion and (2.64 +/-
      0.88) x 102 s-1 with perchlorate as the counterion. The significant difference in
      rate constants for the two anions is probably caused by the ion pairing that
      occurs with lead(II) nitrate.

PMID- 16465707
TI  - A cure for crime: can mental health treatment diversion reduce crime among youth?
AB  - Youth crime is a serious social problem, as is the high proportion of young
      offenders in the juvenile justice system who have mental disorders. A recent
      policy innovation applies the theory of therapeutic jurisprudence and diverts
      youth with mental disorders to treatment in lieu of further court processing. The
      expansion of mental health diversion programs reflects an increasingly popular
      view that there is a causal relationship between youth mental disorders and
      crime. Policymakers who share this view place greater emphasis on rehabilitation
      and treatment as a way to reduce crime, rather than on stricter punishment. This
      paper considers the policy issues around youth mental health diversion programs.
      In addition, it evaluates the effect of a mental health diversion program for
      youth that was implemented in Texas. The paper finds that mental health diversion
      can be used effectively to delay or prevent youth recidivism.

PMID- 16465708
TI  - A strategy for constructing a hybrid bilayer membrane based on a carbon
      substrate.
AB  - We construct a hybrid bilayer membrane (HBM) on a new substrate-carbon electrode.
      It is an extension of HBM based on other substrates. Primary alkylamine was
      chemically modified onto the surface of a carbon electrode by electrochemical
      scans; thus, a monolayer was formed on the electrode. Because the alkane chains
      section is toward the outside, a hydrophobic surface was constructed. Then a
      lipid monolayer was spread on the hydrophobic surface of the carbon electrode.
      The formed HBM was characterized by electrochemical and ATR-FT-IR methods. From
      ATR-FT-IR results, the lipid order parameter (S) of 0.73 was obtained. This kind
      of hybrid membrane has the advantages of a lipid/alkanethiol HBM. A potential
      application of this HBM as a biosensor (detecting K+) was given.

PMID- 16465709
TI  - Application of gas microstrip detectors for X-ray absorption spectroscopy in
      common process gases.
AB  - We report upon the design of a new gas microstrip detector (GMSD) for use in X
      ray absorption spectroscopy applied to the study of catalysis and material
      science. We show that GMSDs can operate not only with the gas mixtures normally
      used in proportional counters but also with the majority of gas mixtures used in
      common catalytic reactions. The detector functions well in the presence of water
      vapor. EXAFS investigations of a test system of NiO on Ni metal are discussed in
      which it is demonstrated that depth profiling using electron yield X-ray
      absorption spectroscopy is possible in a wide variety of gaseous environments.
      Electron detection of XAS using GMSDs is applicable to metals, semiconductors,
      and insulators presented in almost all forms of sample including films, pellets,
      powders, crystals, and liquids.

PMID- 16465710
TI  - Does health technology assessment put patient care at risk?

PMID- 16465711
TI  - Legal, but is it right?

PMID- 16465712
TI  - Topochemical speciation of intercalated palladium in graphite by valence band X
      ray spectrometry in the electron microprobe.
AB  - The binding state of palladium was studied within the frame of an investigation
      on the mechanism of analyte fixation during the pyrolysis step in graphite
      furnace atomic spectrometry. One approach was the determination of the palladium
      intercalated in the pyrolytic coating of the graphite tube. Due to the low
      concentrations of intercalated palladium in the pyrolytic coating, precise
      determination of the shift of certain X-ray lines was chosen. From several
      investigated valence state sensitive X-ray transitions, the Pd Lbeta2/15 (L3
      N4,5) line shift was the one best determinable. The measured line shifts are in
      the range of -0.14 to 0.71 eV at line widths of 13 eV (fwhm) and a line energy of
      3.1729 keV. These very small line shifts were determined by electron probe
      microanalysis. The detection of the small line shifts was performed with a new
      method-by evaluation of the change of the intensity in the flanks of the X-ray
      line. The measurements yielded the following results: inside the pyrolytic
      graphite, the palladium is distributed inhomogeneously in the form of clusters or
      islands and in the form of particles on the surface of the pyrolytic graphite.
      The differentiation between particles and clusters is a very practical one: as
      long as a particle can be seen in the SEM we talk of particles. Often, however,
      Pd is detected in an area on the tube or platform surface without detection of a
      particle. Hence, it can be assumed that the Pd is present in the form of clusters
      which might even be intercalated in the uppermost graphite layers. The valence
      state inside these clusters does not appear to be uniform. It can be interpreted
      as a mixture of Pd with PdO in the center of the clusters or particles (positive
      peak shift) and of Pd bound to the graphite (strong negative peak shift). On the
      basis of these observations, a way is proposed to determine how activated Pd
      atoms in intercalated Pd domains are forming strong covalent bonds to analytes.
      These bonds are responsible for the analyte fixation of even very volatile
      analytes.

PMID- 16465713
TI  - Studies of electron-transfer and charge-transfer coupling processes at a
      liquid/liquid interface by double-barrel micropipet technique.
AB  - Investigation of a heterogeneous electron-transfer (ET) reaction at the water/1,2
      dichloroethane interface employing a double-barrel micropipet technique is
      reported. The chosen system was the reaction between Fe(CN)63- in the aqueous
      phase (W) and ferrocene in 1,2-dichloroethane (DCE). According to the generation
      and the collection currents as well as collection efficiency, the ET-ion-transfer
      (IT) coupling process at such an interface and competing reactions with the
      organic supporting electrolyte in the organic phase can be studied. In addition,
      this technique has been found to be an efficient method to distinguish and
      measure the charge-transfer coupling reaction between two ions (IT-IT) processes
      occurring simultaneously at a liquid/liquid interface. On this basis, the formal
      Gibbs energies of transfer of some ions across the W/DCE interface, such as NO3-,
      NO2-, Cl-, COO-, TBA+, TPAs+, Cs+, Rb+, K+, Na+, and Li+, for which their direct
      transfers are usually difficult to obtain because of the IT-IT coupling
      processes, were quantitatively evaluated.

PMID- 16465714
TI  - Chemical oxidation of p-hydroxyphenylpyruvic acid in aqueous solution by
      capillary electrophoresis with an electrochemiluminescence detection system.
AB  - A system of capillary electrophoresis with electrochemiluminescence detection (CE
      ECL) together with UV spectroscopic and electrochemical methods were used to
      study the chemical oxidation of p-hydroxyphenylpyruvic acid (pHPP) by dissolved
      oxygen in aqueous solution. The pHPP was observed to be readily oxidized by
      dissolved oxygen in alkaline solution and yielded a compound that strongly
      enhanced the electrochemiluminescence of Ru(bpy)23+. This compound was separated
      and detected by a new CE-ECL system and revealed to be oxalate by being compared
      with an authentic sample of oxalate. The chemical oxidation mechanism of pHPP by
      dissolved oxygen was discussed in this paper.

PMID- 16465715
TI  - Selectivity toward multiple predetermined targets in nanoparticle capillary
      electrochromatography.
AB  - Two unique methods to achieve selectivity toward multiple predetermined targets
      employing molecular imprinting technology have been developed. Partial filling
      capillary electrochromatography (CEC) was utilized to evaluate and compare the
      two techniques. The first approach, the mixed singly templated molecularly
      imprinted polymer (MIP) nanoparticle approach, is based on the mixing of two
      types of MIP nanoparticles with inherently different selectivity. The second
      approach, the multiply templated MIP nanoparticle approach, is based on the
      incorporation of two different templates during the preparation of the MIP
      nanoparticles. The use of MIPs in analytical chemistry applications has been
      extensively investigated during the past years. However, MIP nanoparticles with
      tailored multiple selectivity toward predetermined enantiomers has not yet been
      explored. The relative amounts of the two templates studied, i.e., (S)
      ropivacaine and (S)-propranolol, were found to strongly affect the affinity of
      the multiply templated MIP nanoparticles for the predetermined targets. The
      amount of (S)-propranolol template had to be decreased to concentrations rarely
      applied in MIP synthesis in order to achieve 2-fold selectivity. Even though
      strongly decreased to 10% of the usual concentration employed, the MIP could
      efficiently separate the enantiomers of propranolol when applied in partial
      filling CEC. This opens up for new possibilities to decrease the need for an
      initial high amount of template in order to be able to produce an efficient MIP.
      The multiple enantiomer separation ability of the multiply templated MIP
      nanoparticles was compared with that of singly templated MIP nanoparticles that
      were mixed prior to analysis. It was concluded that the multiply templated MIP
      potentially can offer many new and interesting applications in chromatography as
      well as in sensor technology and solid-phase extraction.

PMID- 16465717
TI  - Silver-doped sol-gel film as a surface-enhanced Raman scattering substrate for
      detection of uranyl and neptunyl ions.
AB  - A surface-enhanced Raman scattering (SERS) substrate containing silver particles
      was prepared by an acid-catalyzed sol-gel method. Silver nitrate was first doped
      into the sol-gel film followed by chemical reduction of the silver ions with
      sodium borohydride to produce silver particles. This silver-doped sol-gel
      substrate exhibits strong enhancement of Raman scattering from adsorbed uranyl
      ions with a detection limit of 8.5 x 10(-8) M, which is comparable to existing
      methods of uranyl detection such as spectrophotometry, fluorometry, and a SERS
      method based on ligand-modified solution silver colloids. However, in the present
      method, no preconcentration steps, chromogens, or complexing ligands are needed.
      Compared with the SERS method using Ag colloidal sols, the silver-doped sol-gel
      film has the advantage that the silver particles trapped in the sol-gel matrix
      are much more stable than Ag colloids in liquid media. Furthermore, porous silica
      sol-gel materials are known to have affinities toward many inorganic and organic
      molecules. The enhanced adsorption affinities could also lead to the increased
      SERS sensitivity. The performance of the new silver-doped sol-gel substrate was
      evaluated with uranyl ions and compared to that of a SERS substrate based on
      silver-coated silica beads prepared by vacuum deposition. The detection limit for
      the silver-doped sol-gel film was 104 times lower than that for the silver-coated
      silica beads. The sol-gel substrate was further used to obtain, for the first
      time, the surface-enhanced Raman spectrum of neptunyl ions in dilute aqueous
      solutions.

PMID- 16465716
TI  - Disease-specific expression of VEGF and its receptors in AML cells: possible
      autocrine pathway of VEGF/type1 receptor of VEGF in t(15;17) AML and VEGF/type2
      receptor of VEGF in t(8;21) AML.
AB  - Various angiogenic factors, such as vascular endothelial growth factor (VEGF) and
      an associated molecule, placenta growth factor (PlGF), are thought to be
      important for normal and malignant hematopoiesis. This study examined mRNA
      expression of VEGF, PlGF and receptors for these molecules in AML cells and
      identified the disease-specific patterns of expression. AML M3 having t(15;17)
      abnormality showed highest expression of VEGF and VEGF receptor type 1 (VEGFR1),
      suggesting the autocrine pathway of VEGF-VEGFR1. Then, t(8;21) AML demonstrated
      augmented expression of VEGF and VEGF receptor type 2 (VEGFR2), suggesting VEGF
      VEGFR2 autocrine pathway. Then, addition of VEGFR2 kinase inhibitor in Kasumi-1,
      a t(8;21) AML cell line, resulted in marked inhibition of cell growth, although
      growth inhibitory effect of R2 kinase inhibitor to HL-60 was marginal. In
      addition, cell cycle analysis study showed S-phase cell population reduction by
      R2 kinase inhibitor in Kasumi-1, but not in HL-60. This observation is thought to
      be the rationale for novel molecular target therapy directed to angiogenic
      molecules.

PMID- 16465718
TI  - Determination of polybrominated diphenyl ethers in environmental standard
      reference materials.
AB  - The total concentrations (sigmaPBDE) of 15 polybrominated diphenyl ethers, BDEs
      17, 28, 47, 49, 66, 71, 85, 99, 100, 138, 153, 154, 183, 190, and 209, and a
      predominant polybrominated biphenyl (PBB) congener, 2,2',4,4',5,5'-polybrominated
      biphenyl (PBB-153) were determined in six natural matrix Standard Reference
      Materials (SRM) provided by the National Institute of Standards and Technology
      (NIST). The sigmaPBDE concentrations (+/- one standard deviation) in SRM 1945
      (whale blubber), SRM 1946 (fish tissue), SRM 1947 (fish tissue), and SRM 1974b
      (mussel tissue) were 126 +/- 7, 79 +/- 3, 134 +/- 5, and 7.9 +/- 0.2 ng/g of wet
      wt, respectively. The sigmaPBDE concentrations were 54 +/- 2 and 163 +/- 4 ng/g
      of dry wt for SRM 2977 (mussel tissue) and SRM 2978 (mussel tissue),
      respectively. Among the three kinds of marine animals, mussel tissue had the
      lowest total concentration of PBDEs. These values can provide an informal
      reference or benchmark to laboratories who measure these compounds.

PMID- 16465719
TI  - Are health care providers who work with cancer drugs at an increased risk for
      toxic events? A systematic review and meta-analysis of the literature.
AB  - OBJECTIVE: A systematic review and meta-analysis was conducted to test the
      hypothesis that oncology health care workers are at an increased risk of cancer,
      reproductive complications and acute toxic events. DESIGN: A structured
      literature search of Index Medicus/ MEDLINE, CINAHL, EMBASE, the Cochrane
      Database of Systematic Reviews and Healthstar was performed from 1966 to December
      2004 for human epidemiological studies evaluating the risk of toxic events in
      health care workers exposed to cytotoxic drugs. Raw data and adjusted odds ratios
      (OR) reported in eligible studies were combined using a random effects model to
      calculate point estimates and 95% confidence intervals (CI) for each potential
      risk outcome. MAIN OUTCOME MEASURES: Adjusted OR for congenital malformations,
      stillbirths and spontaneous abortions among health care workers exposure to
      cytotoxic agents compared to a nonexposed control group. RESULTS: The systematic
      review identified 14 studies evaluating the outcomes of interest, seven of which
      were suitable for statistical pooling. Due to lack of evidence, we were unable to
      estimate a pooled OR for the risk of cancer and acute toxic events. However, no
      significant association was detected between exposure to cytotoxic drugs and;
      congenital malformations (OR = 1.64; 95% CI: 0.91-2.94) and stillbirths (OR =
      1.16; 95% CI: 0.73-1.82). In contrast, an association was identified between
      exposure to chemotherapy and spontaneous abortions (OR = 1.46; 95% CI: 1.11
      1.92). CONCLUSIONS: The results of this systematic review identified a small
      incremental risk for spontaneous abortions in female staff working with cytotoxic
      agents. Health policy decision makers should effectively communicate the
      magnitude of this risk to their staff and implement cost effective interventions
      for its reduction or elimination.

PMID- 16465720
TI  - Kinetic studies of cascade reactions in high-throughput systems.
AB  - The application of robotic systems to the study of complex reaction kinetics is
      considered, using the cascade reaction A --> B --> C as a working example.
      Practical problems in calculating the rate constants k1 and k2 for the reactions
      A --> B and B --> C from concentration measurements of CA, CB, or CC are
      discussed in the light of the symmetry and invertability of the rate equations. A
      D-optimal analysis is used to determine the points in time and the species that
      will give the best (i.e., most accurate) results. When exact data are used, the
      most robust solution results from measuring the pair of concentrations (CA, CC).
      The system's information function is computed using numeric methods. This
      function is then used to estimate the amount of information obtainable from a
      given cascade reaction at any given time. The theoretical findings are compared
      with experimental results from a set of two-stage cascade experiments monitored
      using UV-visible spectroscopy. Finally, the pros and cons of using a single
      reaction sample to estimate both k1 and k2 are discussed.

PMID- 16465721
TI  - Stabilization of high-resistance seals in patch-clamp recordings by laminar flow.
AB  - The formation of a high-resistance electrical seal between a cell membrane and a
      glass micropipet tip is essential in patch-clamp experiments. We have studied the
      electrical properties and the mechanical stability of the seal using a
      microfluidic chip generating laminar flow in open volumes. We show that, by using
      fluid flow (1-10 mm/s) acting along the symmetry axis of the cell-pipet, seals of
      a higher mechanical stability with increased resistances can be achieved,
      allowing up to 100% longer recording times and over 40% decreased noise levels
      (Irms). These improved properties are beneficial for high-sensitivity patch-clamp
      recordings, in particular, in longtime studies of ion channel receptor systems
      that are relevant in biosensor applications of the technique. Furthermore, these
      observations support the combination of patch-clamp with microfluidic devices,
      for example, for rapid solution exchange around a single cell sensor for high
      throughput electrophysiology and for highly resolved kinetic studies.

PMID- 16465722
TI  - Quantitative elemental analysis for rhodium and palladium in minerals by time-of
      flight resonance ionization mass spectrometry.
AB  - Results are presented for the trace analysis of Pd and Rh by time-of-flight
      resonance ionization mass spectrometry (TOF-RIMS). The spectrometer, developed at
      the Advanced Mineral Technology Laboratory (Ontario, Canada), is based on a
      commercial laser-induced mass analyzer with upgrades that include independent
      laser ablation and ionization sources and pulsed ion optics to minimize noise
      caused by primary ion formation. The schemes presented for Rh and particularly
      for Pd detection are simpler than others reported in the literature. The
      experimental laser fluences were found to be in reasonable agreement with
      theoretical estimates. The TOF-RIMS measurements were quantified on the basis of
      calibration curves derived using reference samples covering 3 orders of magnitude
      in concentration. Minimum detection limits of ~15 parts per billion were found
      for both metals, with a precision of ~ +/-15%. Samples from sulfide, iron oxide,
      and silicate minerals were also examined. The results are in excellent agreement
      with those obtained using dynamics secondary ion mass spectrometry.

PMID- 16465723
TI  - Fabrication of nanoscale gold disk electrodes using ultrashort pulse etching.
AB  - A novel method for preparing a nanometer-sized gold disk electrode is described.
      The electrode was fabricated by electrochemical etching of a gold wire,
      insulating the etched wire with a varnish with the exception of the apex, and
      cutting down the apex by applying ultrashort (40 ns) etching pulses in an HCl
      solution. Cyclic voltammograms of a 0.10 M ferrocyanide solution recorded at the
      electrode showed that a series of etching pulses gradually reduced the diffusion
      limited current at the electrode by etching its apex. Characterization by cyclic
      voltammetry and scanning electron microscopy revealed the transformation of a
      cone-shaped apex into a disk-shaped electrode with a radius of typically between
      50 and 250 nm.

PMID- 16465724
TI  - A sorptive behavior of monolayer-protected gold nanoparticle films containing
      alkanethiols and alkanedithiols.

PMID- 16465725
TI  - Relationship of bispectral index values, haemodynamic changes and recovery times
      during sevoflurane or propofol anaesthesia in rabbits.
AB  - The aim of this study was to determine and compare the degree of hypnosis
      achieved during propofol or sevoflurane anaesthesia in rabbits using bispectral
      index (BIS), and to evaluate its usefulness as a predictor of both haemodynamic
      changes during anaesthesia and recovery times. Twenty adult male New Zealand
      White rabbits, average weight 4.4 +/- 0.4 kg, were used for this study. Animals
      were randomly allocated to one of two groups with 10 rabbits/group. An
      electroencephalographic recording was obtained from each conscious rabbit prior
      to drug administration. All animals received buprenorphine as a preanaesthetic
      medication (0.05 mg/kg, intravenous [i.v.]). Anaesthesia was induced with
      propofol (8 mg/kg, i.v.) in all animals; 10 rabbits were maintained with
      sevoflurane via inhalation (1 minimum alveolar concentration--end-tidal
      sevoflurane concentration of 3.7%--at a fresh gas flow rate of 3 L/min; group I),
      and 10 were maintained with i.v. propofol (0.6 mg/kg/min; group II). The rabbits
      were orotracheally intubated and spontaneous ventilation was maintained
      throughout the study (100% oxygen). After abdominal surgery through a ventral
      midline laparotomy, rabbits were allowed to recover from anaesthesia.
      Cardiovascular variables and BIS values were recorded at intervals throughout the
      procedure, as was the duration of recovery from anaesthesia. In both groups, mean
      BIS values were significantly decreased immediately after induction, compared
      with baseline values obtained during consciousness. Anaesthetic depth (evaluated
      by clinical observation) was similar in both groups; however, group II rabbits
      had significantly higher (P<0.001) BIS values from 30 s before incision until
      anaesthesia was discontinued. There was no significant difference in BIS recorded
      1 and 5 min after incision as compared with values obtained 30 s before incision
      in either group. During sevoflurane or propofol administration, correlations were
      found between BIS values and mean arterial blood pressure (MABP), and between BIS
      values and heart rate (HR). Mean BIS values at discontinuation of administration
      of the anaesthetic agent were greater in group II (69.1 +/- 6.0) than in group I
      (49.3 +/- 2.2). However, recovery from anaesthesia was significantly longer in
      group II (38.4 +/- 7.2 min) than in group I (11.5 +/- 2.5 min). In conclusion,
      BIS can be used to differentiate between conscious and unconscious states during
      anaesthesia in rabbits. BIS values derived from an electroencephalogram at the
      end of anaesthesia were not useful for predicting the speed of anaesthetic
      recovery in sevoflurane or propofol-anaesthetized rabbits undergoing abdominal
      surgery. Despite the correlation found between BIS and haemodynamic parameters,
      its usefulness as a predictor of clinically important changes in arterial blood
      pressure and HR in anaesthetized rabbits was limited.

PMID- 16465726
TI  - Caregiver satisfaction with support services: influence of different types of
      services.
AB  - OBJECTIVES: This article examines factors influencing satisfaction with support
      services of caregivers of frail older adults and determines what types of support
      services are associated with greater satisfaction, controlling for frail
      individual and caregiver characteristics. METHODS: The study includes 291 frail
      older adults-caregiver dyads from Montreal in which caregivers receive support
      services. The Client Satisfaction Questionnaire-8 is used to measure caregiver
      satisfaction with these services. RESULTS: Caregivers receiving information,
      advice, or emotional support, and those caring for seniors receiving integrated
      care are more likely to be highly satisfied. Other factors increasing
      satisfaction are fewer number of health problems of frail individuals, caregiver
      being the spouse of the frail person, as well as greater caregiver perceived
      health, autonomy in instrumental activities of daily living, and available social
      support. DISCUSSION: The results support the importance of integrated care for
      frail seniors and informational services for their caregivers.

PMID- 16465727
TI  - Nature, not books: scientists and the origins of the nature-study movement in the
      1890s.
AB  - Scientists played a key role in the first systematic introduction of nature study
      into North American public schools in the late nineteenth century. The
      initiatives of Wilbur Jackman and John Merle Coulter, affiliated with the young
      University of Chicago, and Liberty Hyde Bailey and Anna Botsford Comstock, at
      Cornell University, coincided with the "new education" reform movement that found
      object lessons and experience-based education superior to textbook teaching.
      Educational psychologists and philosophers of the 1890s, including G. Stanley
      Hall, related curriculum methods to perceived developmental stages in children,
      with a focus on immediate experience. Putting these pedagogical ideas--gained in
      summer institutes, normal schools, and programs at Chicago and Cornell--into
      practice were administrators and classroom teachers in both urban and rural
      classrooms. By 1900, a consensus about the value of nature study among
      scientists, community leaders, and teachers established it as the recognized
      general method of studying the natural world in public schools across much of the
      United States.

PMID- 16465728
TI  - Turning science to account: Chicago and the general science movement in secondary
      education, 1905-1920.
AB  - In the second decade of the twentieth century a new subject appeared in American
      high schools, aimed at providing citizens with an understanding of the essential
      nature of scientific thinking. "General science," as it was called, was developed
      and promoted by an emerging class of professional educators who sought to offer a
      version of science that they believed would both excite public interest and prove
      useful in the everyday lives of the masses of students streaming into the rapidly
      expanding institution of secondary education. It was to be a course with real
      utility that would transcend the boundaries of the specialized, abstract
      disciplinary subjects like chemistry and physics-subjects with identities tied to
      the practices and standards of the colleges and universities, which had long
      exerted control over the content of secondary schooling. This essay recounts the
      origins of general science and, in particular, examines how the intellectual and
      material environment of the city of Chicago at the turn of the century influenced
      the course that was produced and widely adopted in school programs across the
      United States.

PMID- 16465729
TI  - Classification of mosquitoes in tribe Aedini (Diptera: Culicidae):
      Paraphylyphobia, and classification versus cladistic analysis.
AB  - Many mosquito species are important vectors of human and animal diseases, and
      others are important nuisance species. To facilitate communication and
      information exchange among professional groups interested in vector-borne
      diseases, it is essential that a stable nomenclature be maintained. For the
      Culicidae, easily identifiable genera based on morphology are an asset. Major
      changes in generic concept, the elevation of 32 subgenera within Aedes to generic
      status, and changes in hundreds of species names proposed in a recent article
      demand consideration by all parties interested in mosquito-borne diseases. The
      entire approach to Aedini systematics of these authors was flawed by an
      inordinate fear of paraphyletic taxa or Paraphylyphobia, and their inability to
      distinguish between classification and cladistic analysis. Taxonomists should
      refrain from making taxonomic changes based on preliminary data, and they should
      be very selective in assigning generic names to only the most important and well
      defined groups of species.

PMID- 16465730
TI  - Lutzomyia longipalpis peritrophic matrix: formation, structure, and chemical
      composition.
AB  - Sandflies are vectors of several pathogens, constituting serious health problems.
      Lutzomyia longipalpis (Lutz & Neiva, 1912) is the main vector of Leishmania
      chagasi, agent of visceral leishmaniasis. They synthesize a thick bag-like
      structure that surrounds the bloodmeal, named peritrophic matrix (PM). One of the
      major roles of PM in blood-fed insects includes protection against ingested
      pathogens by providing a defensive barrier to their development. We used
      traditional and modern morphological methods as well as biochemical and
      immunolabeling tools to define details of the PM structure of the Lu. longipalpis
      sandfly, including composition, synthesis, and degradation. The kinetics of PM
      formation and degradation was found to be related to the ingestion and time of
      digestion of the bloodmeal. The midgut changes its size and morphology after the
      blood ingestion and during the course of digestion. A striking morphological
      modification takes place in the midgut epithelium after the stretching caused by
      the bloodmeal, revealing a population of cells that was not observed in the unfed
      midgut. The transmission and scanning electron microscopies were used to reveal
      several morphological aspects of PM formation. The PM looks thicker and well
      formed 24 h after the bloodmeal. Presence of chitin in the PM was demonstrated by
      immunolabeling with an alpha-chitin monoclonal antibody. SDS-polyacrylamide gel
      electrophoresis showed at least five protein bands with molecular masses of 38.7
      135 kDa, induced by the protein-free diet. Mouse polyclonal antiserum was
      produced against PMs induced by protein-free meal and used in Western blotting,
      which revealed at least three associated proteins.

PMID- 16465731
TI  - Meconial peritrophic matrix structure, formation, and meconial degeneration in
      mosquito pupae/pharate adults: histological and ultrastructural aspects.
AB  - The noncellular peritrophic matrix (PM) that forms around the food bolus in the
      midgut of many arthropod species may influence the fate of ingested microbes. In
      mosquitoes, PMs have been identified in the pupal as well as larval and adult
      stages. In pupae, the PMs surround the meconium, the sloughed larval midgut
      epithelium. Meconial PM1 (MPM1) forms early in the pupal stadium, and a second
      meconial PM (MPM2) sometimes forms around the time of adult emergence. A recent
      study suggests that MPMs contribute to the sterilization of the adult midgut by
      sequestering microorganisms ingested during the larval stage, which, along with
      remaining meconial material, are egested after adult emergence. We have compared
      MPM1 formation and patterns of meconial degeneration in representative species in
      five mosquito genera and identified a temporal association between MPM1
      formation, meconial degeneration, and apolysis. Ultrastructural study of MPM1 and
      MPM2 in Aedes aegypti (L.) revealed that MPM1 seems to be structurally different
      from either the larval or adult PMs, whereas MPM2 more closely resembles PM
      formed around a bloodmeal in adult females. Our results are consistent with the
      microbial sequestration role.

PMID- 16465732
TI  - First report of the male of Amblyomma rotundatum (Acari: Ixodidae) from a field
      collected host.
AB  - An adult male of the tick Amblyomma rotundatum Koch was collected on a naturally
      infested lizard, Tropidurus sp. (Squamata: Tropiduridae), at Monte Negro, State
      of Rondonia, Brazil. The tick's identity was confirmed morphologically and by
      analysis of the second internal transcribed spacer of the ribosomal DNA. This is
      the third known male specimen of A. rotundatum, a species that has been shown to
      reproduce exclusively by parthenogenesis. The two previously reported male
      specimens seemed to be partially teratological or gynandromorphic, whereas the
      present specimen shows no visible genetic or developmental anomaly.

PMID- 16465733
TI  - First description of a new species of Demodex (Acari: Demodecidae) from rhesus
      monkey.
AB  - Species of Demodex live in hair follicles and sebaceous glands of many species of
      mammals. Demodex macaci n .sp. is described (all life stages) from a captive
      rhesus monkey, Macaca mulatta (Zimmermann, 1780). Mites were found at all levels
      of the hair follicles and occasionally in sebaceous glands of the skin of the
      perineal region. This is the first description of a demodectic hair follicle mite
      from the primate family Cercopithecidae.

PMID- 16465734
TI  - Systematics and identification of Afrotropical Toxorhynchitinae (Diptera:
      Culicidae).
AB  - I define two new species groups of Afrorhynchus from the Afrotropical Region and
      examine the taxonomic structure of the genus in the region. Keys are provided for
      the identification of adult males and females of all known Afrotropical
      Toxorhynchites.

PMID- 16465735
TI  - Effects of temperature on the rate of increase of Stomoxys calcitrans and
      Stomoxys niger niger (Diptera: Muscidae) from La Reunion island.
AB  - Adult survival and reproduction were compared between two Stomoxys species that
      co-occur in La Reunion, the cosmopolitan Stomoxys calcitrans (L.), and the
      tropical Stomoxys niger niger Macquart. In a first experiment, mean longevity and
      fecundity were determined at five constant temperatures from 15 to 35 degrees C,
      after development at the same temperatures. Adult longevity was greatest at 20
      degrees C in S. calcitrans and at 15 degrees C in S. niger. Adult S. niger
      survived longer than adult S. calcitrans, especially at 15 degrees C. At 35
      degrees C, all flies died within 3 d. Reproduction occurred only within the 20-30
      degrees C range, and S. niger laid more eggs than S. calcitrans. In both species,
      lifetime fecundity tended to decrease when temperature increased, because of the
      shortening of the oviposition period. In a second experiment, adults were
      maintained at 15 degrees C after development at 25 degrees C. The higher
      temperature during development significantly increased adult longevity in S.
      calcitrans but not in S. niger. Reproduction occurred at 15 degrees C, with
      notable fecundity in S. calcitrans (22 eggs per female) but not in S. niger (<1
      egg per female). Using previous results on immature survival and developmental
      time in the two species, several life history parameters were compared at each
      temperature. Generation time decreased with increasing temperature and was highly
      similar in both species. Concurrently, the intrinsic rate of increase (r)
      increased with temperature from 15 to 30 degrees C. At 15 degrees C, r was higher
      in S. calcitrans, but within the 20-30 degrees C range, r was higher in S. niger.
      The results suggest 1) S. niger has evolved a strategy of survival without any
      reproduction during the tropical winter, in contrast with S. calcitrans that
      breeds more continuously; and 2) S. niger may outnumber S. calcitrans in warm
      areas, at least when development occurs in media of poor quality.

PMID- 16465736
TI  - Host associations of Ixodes scapularis (Acari: Ixodidae) in residential and
      natural settings in a Lyme disease-endemic area in New Jersey.
AB  - We live-trapped small mammals and flagged vegetation within wooded natural and
      residential landscapes to examine how any observed differences in small mammal
      species composition may influence Ixodes scapularis Say burdens and the abundance
      of host-seeking ticks. Two years of live trapping showed that Eastern chipmunks,
      Tamias striatus, were captured with significantly greater frequency in some
      residential areas than white-footed mice, Peromyscus leucopus, whereas the
      proportion of white-footed mouse captures was higher or similar to chipmunk
      captures in the undeveloped natural areas. Both mice and chipmunks seemed to
      adapt well to managed residential landscapes, with residential sites yielding
      similar or significantly greater numbers of captures compared with undeveloped
      sites. In areas where chipmunk captures outnumbered mice, larval tick burdens on
      mice were either higher or no different than in areas where few or no chipmunks
      were captured, in contrast to previous studies suggesting that alternate hosts
      should reduce larval burdens on mice. Chipmunks apparently play an important role
      in the Lyme disease transmission cycle in these residential settings.

PMID- 16465737
TI  - Effects of microclimatic changes caused by land use and land cover on duration of
      gonotrophic cycles of Anopheles gambiae (Diptera: Culicidae) in western Kenya
      highlands.
AB  - Studies were carried out at a malaria epidemic-prone highland site in western
      Kenya to determine the effects of deforestation-caused microclimate change on the
      duration of the gonotrophic cycle of the malaria vector Anopheles gambiae Giles.
      Gonotrophic cycle duration was measured using field-collected F1 A. gambiae
      females. Average ambient temperature in the deforested area of Kakamega
      (elevation 1,430-1,580 m above sea level), western Kenya, was 0.5 degrees C
      higher than that of the forested area over a 10-mo period. During the dry season,
      deforested areas showed an increased mean indoor temperature of 1.8 degrees C,
      and a shortened duration of the mosquitoes' first and second gonotrophic cycles,
      by 1.7 d (59%) and 0.9 d (43%). During the rainy season, the average indoor
      temperature of houses located in the deforested area was 1.2 degrees C higher
      than in houses in the forested area. The duration of the first and second
      gonotrophic cycles was shortened by 1.5 d (17%) and 1.4 d (27%), respectively, in
      the deforested highland site. A shorter mosquito gonotrophic cycle implies
      increased daily biting frequency and thus increased vectorial capacity. Together
      with evidence that deforestation reduced A. gambiae larva-to-adult developmental
      time and increased larval and adult survivorship, this study suggests that
      deforestation can further enhance malaria transmission potential in the highlands
      through increased indoor temperature and shortened gonotrophic cycle durations of
      A. gambiae mosquitoes.

PMID- 16465738
TI  - Feeding patterns of Haemagogus janthinomys (Diptera: Culicidae) in different
      regions of Brazil.
AB  - New data on the feeding patterns of Haemagogus (Haemagogus) janthinomys Dyar from
      different geographical regions of Brazil, by using the precipitin test as the
      bloodmeal-identifying tool, are presented. The following antisera were used:
      bird, dog, human, rodent, cattle, horse, and opossum. The origins of 287
      bloodmeals were identified, whereas 33 specimens were negative to the antiserums
      tested. Among the reactive specimens, 174 (60.6%) fed on only one food source, of
      which 35.1% originated from birds, 19.5% from rodents, 12.6% from humans, 10.3%
      from cattle, 10.3% from opossums, 7.5% from dogs, and 4.6% from horses. One
      hundred six (37.0%) mosquitoes fed on two sources, of which the most common
      combinations were bird + rodent (16.0%), bird + human (10.4%), and horse + human
      (9.4%). Seven (2.4%) mosquitoes fed on three different hosts. Our results suggest
      that Hg. janthinomys is more eclectic and opportunist than previously known in
      relation to its hosts and that such patterns are probably highly adaptive to a
      temporally and spatially variable environment.

PMID- 16465739
TI  - Nocturnal activity rhythms of Lutzomyia intermedia and Lutzomyia whitmani
      (Diptera: Psychodidae) in a transmission area of American cutaneous leishmaniasis
      in Rio de Janeiro State, Brazil.
AB  - The phlebotomine sand flies Lutzomyia (Nyssomyia) intermedia (Lutz & Neiva) and
      Lutzomyia (Nyssomyia) whitmani (Coutinho & Antunes) are important vectors of
      Leishmania (Vianna) braziliensis, the etiological agent of American cutaneous
      leishmaniasis. In some areas, both species occur in sympatry, and their relative
      roles as vectors in these areas are not clear. We studied the nocturnal activity
      and biting rhythms of both species in Posse, a locality in Rio de Janeiro State,
      Brazil. Our results show differences between the activity patterns of Lu.
      intermedia and Lu. whitmani that might be epidemiologically important. Although
      the activity profiles vary between seasons and microhabitats (peridomestic versus
      forest), the two species show marked differences in their tendencies to bite
      humans in the early morning (0400-0600 hours), with Lu. whitmani showing higher
      feeding rates than Lu. intermedia.

PMID- 16465740
TI  - Oviposition site preference and egg hatchability of Anopheles gambiae: effects of
      land cover types.
AB  - We studied the oviposition site preference and egg hatchability of Anopheles
      gambiae Giles with water collected from farmlands, forests, and natural wetlands.
      Water types significantly affected oviposition preference. Mosquitoes deposited
      significantly more eggs in rainwater in both the dry and wet seasons than waters
      from forests and wetlands, suggesting that An. gambiae prefers water with few
      impurities for oviposition. In the dry season, An. gambiae females also deposited
      significantly more eggs in waters from farmlands than those from forests and
      natural wetlands, but these differences were not statistically significant during
      the wet season. In both indoor and natural conditions, egg mortality in natural
      wetland habitats was significantly higher than in farmland habitats. The average
      water temperature in natural wetland habitats was significantly lower than
      farmland habitats in the natural conditions, but it remained the same under
      indoor experimental conditions, suggesting that factors other than water
      temperature play an important role in egg hatchability. Together with the
      findings from previous studies on the effects of land cover on larval
      survivorship, our results support the hypothesis that variations in habitat
      conditions induced by different land cover types contribute to the heterogeneous
      spatial distribution of An. gambiae larvae in the western Kenya highland.

PMID- 16465741
TI  - Species and populations of the Anopheles gambiae complex in Cameroon with special
      emphasis on chromosomal and molecular forms of Anopheles gambiae s.s.
AB  - We studied the geographical distribution of species, chromosomal, and molecular
      forms of the Anopheles gambiae Giles (Diptera: Culicidae) complex in 23 sites in
      Cameroon, Central Africa. Almost all the specimens collected in the four northern
      most arid sites were Anopheles arabiensis. Anopheles melas was found in a rural
      locality surrounded by mangrove swamps, on the Atlantic Coast. In total, 1,525
      An. gambiae s.s. females were identified down to their molecular form, and
      inversion polymorphisms on polytene chromosomes were scored from 186 half-gravid
      females. The Forest chromosomal form, with standard arrangements almost fixed on
      both arms of chromosome-2, was the only one observed in the southern, more humid
      localities. Karyotypes typical of Savanna and Mopti were recorded northwards, in
      the humid savannas of the Adamawa Province. The molecular forms M and S were
      widespread throughout Cameroon, and assort independently from the chromosomal
      forms. S-form populations were characterized by karyotypes typical of Forest and
      Savanna chromosomal forms, and M-form populations were characterized by
      karyotypes typical of Forest, Savanna, and Mopti. No M/S hybrid patterns were
      detected, although M and S mosquitoes were sympatric in 15 sites, providing
      further evidence for positive assortative mating within molecular forms. The
      observed ecogeographical distribution of M and S was peculiar: the ecological
      parameters involved in this distribution still need to be clarified as well as
      the possible role of competitive exclusion between chromosomally homosequential
      molecular forms. No difference was observed in host preference or in Plasmodium
      falciparum infection rates between sympatric M and S populations.

PMID- 16465742
TI  - Development of an adaptive tsetse population management scheme for the Luke
      community, Ethiopia.
AB  - Since 1996, tsetse (Glossina spp.) control operations, using odor-baited traps,
      have been carried out in the Luke area of Gurage zone, southwestern Ethiopia.
      Glossina morsitans submorsitans Newstead was identified as the dominant species
      in the area, but the presence of Glossina fuscipes Newstead and Glossina
      pallidipes Austen also was recorded. Here, we refer to the combined number of
      these three species and report the work undertaken from October 2002 to October
      2004 to render the control system more efficient by reducing the number of traps
      used and maintaining the previously reached levels of tsetse occurrence and
      trypanosomiasis prevalence. This was done by the design and implementation of an
      adaptive tsetse population management system. It consists first of an efficient
      community-participatory monitoring scheme that allowed us to reduce the number of
      traps used from 216 to 127 (107 monitoring traps and 20 control traps).
      Geostatistical methods, including kriging and mapping, furthermore allowed
      identification and monitoring of the spatiotemporal dynamics of patches with
      increased fly densities, referred to as hot spots. To respond to hot spots, the
      Luke community was advised and assisted in control trap deployment. Adaptive
      management was shown to be more efficient than the previously used mass trapping
      system. In that context, trap numbers could be reduced substantially, at the same
      time maintaining previously achieved levels of tsetse occurrences and disease
      prevalence.

PMID- 16465743
TI  - Roles played by esterase activity and by a sodium channel mutation involved in
      pyrethroid resistance in populations of Boophilus microplus (Acari: Ixodidae)
      collected from Yucatan, Mexico.
AB  - Pyrethroid resistance in Boophilus microplus (Canestrini) (Acari: Ixodidae) was
      studied by correlating discriminating-dose (DD) bioassay results and esterase
      activity or the frequency of a sodium channel mutation known to be involved in
      pyrethroid resistance in nine field strains of B. microplus from Yucatan, Mexico.
      Two tick strains (P67 and B74) were identified as susceptible to cypermethrin,
      deltamethrin, and flumethrin by DD, one strain (P65) was susceptible to
      cypermethrin and resistant to deltamethrin and flumethrin, and six strains were
      resistant to cypermethrin, delta-methrin, and flumethrin (T11, M10, C54, R49,
      B71, and T66). By using polymerase chain reaction, only 6.0 and 6.2% of
      resistance allele (R) was found in the susceptible strains (P67 and B74,
      respectively). In the T66 strain, with 100% of larval survival to the DD of
      pyrethroids as measured by the larval packet test (LPT), 98.0% of the gene pool
      contained the R allele. Positive correlations between the larval survival and the
      percentage of the R allele were found (deltamethrin r2 = 0.8875, P < 0.01;
      cypermethrin r2 = 0.8563, P < 0.01; and flumethrin r2 = 0.8491, P < 0.01). There
      were no significant correlations between the level of larval survival and
      esterase-based hydrolytic activity. It was concluded that within the B. microplus
      populations studied, resistance to flumethrin, deltamethrin, or cypermethrin was
      because of the novel sodium channel mutation (Phe-->Ile amino acid substitution
      in the S6 transmembrane segment of domain III), and there was a correlation
      between tick mortality by pyrethroid exposure (larval survival) and the presence
      of R allele. It was not determined whether enhanced esterase-based hydrolytic
      activity was involved in pyrethroid resistance in the populations tested.

PMID- 16465744
TI  - Differentiation of Culicoides obsoletus and Culicoides scoticus (Diptera:
      Ceratopogonidae) based on mitochondrial cytochrome oxidase subunit I.
AB  - Culicoides obsoletus (Meigen) and Culicoides scoticus Downes & Kettle (Diptera:
      Ceratopogonidae) are sibling species of the Obsoletus group. This group comprises
      species of biting midges that are suspect vectors of bluetongue virus (family
      Reoviridae, genus Orbivirus, BTV) and African horse sickness virus (family
      Reoviridae, genus Orbivirus, AHSV). BTV and AHSV have been isolated several times
      from females of this group, although it has not been possible to determine the
      particular species harboring the virus, because of the inability to clearly
      identify the females of each species based on morphology. Both sexes of C.
      obsoletus and C. scoticus midges from Catalonia and the Balearics (Spain) were
      sequenced for the mitochondrial gene cytochrome oxidase subunit I (COI), and
      these sequences were analyzed to determine intra- and interspecific genetic
      variability. Species-specific primers for C. obsoletus and C. scoticus were
      designed and a polymerase chain reaction (PCR)-based diagnostic assay based on
      the COI gene and using a hemi-nested PCR technique was developed for reliably
      distinguishing the females of both species. The species-specific PCR diagnostic
      was compared with morphological discrimination of C. obsoletus and C. scoticus
      females. The morphologic characters were not fully reliable.

PMID- 16465745
TI  - Ability of trypanosome-infected tsetse flies (Diptera: Glossinidae) to acquire an
      infection with a second trypanosome species.
AB  - The epidemiology of human and animal trypanosomiasis is determined to a large
      extent by the number of infected tsetse flies in a specific area. In the field, a
      substantial proportion of infected flies carry mixed trypanosome infections. The
      way in which these tsetse flies acquire a mixed infection is not fully
      understood. In particular, the susceptibility of tsetse flies to sequential
      infection with trypanosomes is not well understood. Accordingly, laboratory
      studies were made of the effects of age and prior infection on the probability of
      Glossina morsitans morsitans (Westwood) developing an infection of Trypanosoma
      congolense and Trypanosoma brucei brucei after feeding on infected mice. Results
      of these experiments clearly showed that 20-30-d-old G. m. morsitans can still
      pick up and develop a mature infection in the mouthparts/hypopharynx for T.
      congolense or in the salivary glands for T. b. brucei. However, their ability to
      acquire infection was significantly lower compared with teneral flies.
      Furthermore, 20-30-d-old flies that already carry a mature T. congolense or T. b.
      brucei infection remained at least as susceptible to a secondary trypanosome
      infection compared with noninfected flies of the same age. The immunological and
      epidemiological repercussions of those findings are discussed.

PMID- 16465746
TI  - Sentinel pigeon surveillance for West Nile virus by using lard-can traps at
      differing elevations and canopy cover classes.
AB  - Sentinel pigeons, Columba livia, were installed in lard-can traps at heights of
      1.5 m and 7.6-9.1 m within differing canopy cover classes in New York City. Adult
      mosquitoes were collected weekly from July to October 2002, as were serum samples
      from each pigeon. Culex pipiens L. and Culex restuans Theobald comprised 97% of
      mosquitoes collected and were most numerous in canopy-level, forested traps. The
      West Nile virus (family Flaviviridae, genus Flavivirus, WNV) seroconversion rate
      was significantly greater for pigeons in canopy-level traps, although
      seroconversions occurred concurrently with human cases in the city and were of
      little prognostic value to public health agencies. Our results indicate that
      sentinel pigeons were most effective for monitoring enzootic transmission of WNV
      when placed in single-sentinel caging 7.6-9.1 m above ground level.

PMID- 16465747
TI  - Aedes aegypti (L.) and Aedes polynesiensis Marks (Diptera: Culicidae) in Moorea,
      French Polynesia: a study of adult population structures and pathogen (Wuchereria
      bancrofti and Dirofilaria immitis) infection rates to indicate regional and
      seasonal epidemiological risk for dengue and filariasis.
AB  - Populations of Aedes aegypti (L.) and Aedes polynesiensis (Marks) on Moorea
      Island, French Polynesia, the local vectors of dengue and filariasis,
      respectively, were sampled by landing/biting collection at nine localities on the
      east, north, and west coasts, during the late dry season, early and late wet
      season (September-May) 2003 and 2004, to investigate epidemiologically important
      features of the populations and compare them between regions and months. Biting
      rates of both species tended to increase (but not always significantly) for each
      species in each region each month from the late dry season to the late wet
      season, and the north coast region had significantly higher biting rates of Ae.
      aegypti. Insemination rates of Ae. polynesiensis females (94.5-98.8%) were
      consistently greater than those of Ae. aegypti (87.5-93.5%) throughout the study,
      but there was no significant difference in the insemination rates of either
      species between months and regions. Parity rates were generally highest in north
      coast samples and lowest in west coast samples for both species and generally
      increased (albeit not always significantly) by month for each species, with a
      range of 52.9-88.8% for Ae. polynesiensis and 28.6-53.6% for Ae. aegypti,
      although the high gravid rate (15.8-45.9%) of Ae. aegypti samples (reflecting its
      feeding more than once in a gonotrophic cycle) confounded both intraspecific and
      interspecific comparisons. Filarial infection was rare in Ae. aegypti, although
      both W. bancrofti and D. immitis were recorded, and infection rates in Ae.
      polynesiensis increased through the study period in each region for both
      filarias, with up to 4.6% infected and 1.4% infective for W. bancrofti and up to
      6.3% infected and 2.5% infective for D. immitis. For W. bancrofti, infection
      rates were significantly lower on the west coast and also in the dry season,
      whereas rates for infective stages were significantly greater in the late wet
      season. For D. immitis there was no significant difference in infection rates
      between regions, but rates were significantly greater in the late wet season.
      Rainfall in all months sustains populations of both vectors and explains the
      relatively few significant differences between seasons; however, the wet season
      may provide for increased vector abundance and longevity, and present a
      potentially increased risk for transmission. Although the differences shown
      between regions also were limited in a statistical sense, there were increased
      risks for the northern and eastern regions, where both locals and tourists are
      concentrated and where the seaports and airport are located, and these areas
      should be priority targets for disease surveillance and vector control.

PMID- 16465749
TI  - High-throughput molecular testing of ticks using a liquid-handling robot.
AB  - To meet the need for high-throughput sample testing, DNA extraction kits based on
      the 96-well plate format have been developed for use with blood and tissue
      samples. These methods have not been applied to DNA extractions from ticks. To
      meet this need, we developed a high-throughput method for DNA extraction and
      polymerase chain reaction (PCR) testing of tick samples. A liquid-handling robot
      was used to extract DNA in a 96-well binding column plate with vacuum manifold.
      The quantity, purity, and quality of DNA recovered from Ixodes scapularis Say,
      1821 nymphs with this method were reproducible and comparable with existing
      manual DNA extraction techniques. The DNA yield from pools of five nymphal ticks
      averaged 0.432 +/- 0.04 microg (95% CI). The robot also prepared real-time PCR
      reactions in 96-well plates, directly from the extracted DNA. A modification of
      the existing P20 tool resulted in accurate pipetting of 1- to 2-microl volumes
      with a reproducibility of +/- 0.038 microl when dispensing 1.0 microl. By using
      this process, 96 samples can be extracted and tested while reducing human labor
      to approximately 30 min.

PMID- 16465748
TI  - Three multiplex assays for detection of Borrelia burgdorferi sensu lato and
      Borrelia miyamotoi sensu lato in field-collected Ixodes nymphs in North America.
AB  - Two hundred fifty New Jersey field-collected Ixodes scapularis Say ticks and 17
      Colorado Ixodes spinipalpis Hadwen & Nuttall ticks were tested using three
      separate multiplex real-time polymerase chain reaction (PCR) assays. One assay
      targets the rrs-rrlA IGS region of Borrelia spp. to detect Borrelia burgdorferi
      sensu lato (s.l.) and Borrelia miyamotoi s.l. The second assay targets the ospA
      region of B. burgdorferi s.l. to detect B. burgdorferi sensu stricto (s.s.),
      Borrelia bissettii, and Borrelia andersonii. The final assay targets the glpQ
      region of B. miyamotoi s.l. to differentiate B. miyamotoi LB-2001 and Borrelia
      lonestari. A testing scheme combining these tests yielded 18% of tested I.
      scapularis ticks surveyed from New Jersey positive for B. burgdorferi s.s., 3.2%
      I. scapularis ticks positive for B. miyamotoi LB-2001, and 41.2% I. spinipalpis
      ticks positive for B. bissettii surveyed from Colorado.

PMID- 16465750
TI  - Fine-scale predictions of distributions of Chagas disease vectors in the state of
      Guanajuato, Mexico.
AB  - One of the most daunting challenges for Chagas disease surveillance and control
      in Mexico is the lack of community level data on vector distributions. Although
      many states now have assembled representative domestic triatomine collections,
      only two triatomine specimens had been collected and reported previously from the
      state of Guanajuato. Field personnel from the state's Secretaria de Salud
      conducted health promotion activities in 43 of the 46 counties in the state and
      received donations of a total of 2,522 triatomine specimens between 1998 and
      2002. All specimens were identified, and live insects examined for Trypanosoma
      cruzi. In an effort to develop fine-scale distributional data for Guanajuato,
      collection localities were georeferenced and ecological niches were modeled for
      each species by using evolutionary-computing approaches. Five species were
      collected: Triatoma mexicana (Herrich-Schaeffer), Triatoma longipennis (Usinger),
      Triatoma pallidipennis (Stal), Triatoma barberi (Usinger), and Triatoma dimidiata
      (Latreille) from 201 communities located at elevations of 870-2,200 m. Based on
      collection success, T. mexicana had the broadest dispersion, although niche
      mapping indicates that T. barberi represents the greatest risk for transmission
      of Chagas disease in the state. T. dimidiata was represented in collections by a
      single adult collected from one village outside the predicted area for all
      species. For humans, an estimated 3,755,380 individuals are at risk for vector
      transmission in the state, with an incidence of 3,500 new cases per year; overall
      seroprevalences of 2.6% indicate that 97,640 individuals are infected with T.
      cruzi at present, including 29,300 chronic cases.

PMID- 16465751
TI  - Description of male Loxosceles mulege Gertsch & Ennik 1983 (Araneae: Sicariidae)
      of Baja California.
AB  - The first known males of spider Loxosceles mulege Gertsch & Ennik from the
      xerophilous shrub vegetation zone of Baja California Sur, Mexico, are described.

PMID- 16465752
TI  - Monitoring of Japanese encephalitis virus infection in mosquitoes (Diptera:
      Culicidae) at Guandu Nature Park, Taipei, 2002-2004.
AB  - Japanese encephalitis virus (JEV) infection in mosquitoes was monitored at Guandu
      Nature Park in Taipei City from September 2002 to December 2004. In total, 30,386
      female mosquitoes consisting of six genera and 14 species were processed for
      virus in 1,229 pools by using Flavivirus NS5 gene sequences detected by reverse
      transcription-polymerase chain reaction (PCR) and nested PCR assay. Overall, 101
      pools were positive, including 95, 1, 4, and 1 for Culex tritaeniorhynchus Giles,
      Culex sitiens Wiedemann, Culex rubithoracis (Leicester), and Aedes vexans
      noctunmus (Theobald), respectively.

PMID- 16465754
TI  - [The connection famine--schizophrenia. The unborn child's risk of disease is
      doubled when the mother is starving].

PMID- 16465753
TI  - [Epidemiology and sick building syndrome--an unsuitable combination].

PMID- 16465755
TI  - [Multiple epiphyseal dysplasia. Early diagnosis important for genetic risk
      assessment, preventive measures and injury-reducing treatment].

PMID- 16465757
TI  - [Primary health care plays an important role in mental illness. A consecutive
      cross-sectional study in Gothenburg points out extensive needs for development].

PMID- 16465756
TI  - [Primary prevention in hypercholesterolemia. High HDL cholesterol levels and
      female gender underestimated protective factors].

PMID- 16465758
TI  - [The burden of disease in Sweden measured with DALY. Neuropsychiatric diseases
      and cardiovascular diseases dominate].

PMID- 16465759
TI  - [Putting a P for fraud].

PMID- 16465760
TI  - [The National Board of Health and Welfare replies to the criticism: it must be
      possible to express and assess the anxiety that children are exploited during the
      asylum seeking process].

PMID- 16465761
TI  - [To have more physicians in executive functions requires changes in the
      curriculum of undergraduate medical education].

PMID- 16465762
TI  - [Time for the medical profession to show determination in leadership issues!].

PMID- 16465763
TI  - [Unite medical knowledge with economics and administration!].

PMID- 16465764
TI  - [Can physicians resume their role in health care?].

PMID- 16465765
TI  - [About "sick listing"].

PMID- 16465766
TI  - [Artistry with health care motifs].

PMID- 16465767
TI  - European Neuropathology--a scientific epistemology.

PMID- 16465768
TI  - Neuropathology in Europe: an overview.
AB  - After a short historical review covering the past 150 years, different aspects of
      training and practice are considered. Prominent institutes, men and women who
      have made significant contributions to neuropathology are considered although
      those still living are not included. There are those countries with
      neuropathology as a speciality, countries with subspecialty and those countries
      without neuropathology as a speciality or subspeciality. In order to harmonize
      teaching, training, examinations and regulations, EURO-CNS (European
      Confederation of Neuropathological Societies) was founded in 1993. This allowed
      the recognition of the training charter of neuropathology by the Board of
      Pathology (1998), the organization of European courses and European congresses,
      and the achievement of concerted actions simultaneously, recognition of the
      subspecialty of Neuropathology by the UEMS (Union Europeenne des Medecins
      Specialistes) Council was obtained in 1997. Data relating to the current position
      of neuropathology are included and the future of education and the challenges
      facing neuropathology are discussed.

PMID- 16465769
TI  - Early onset parkinsonism in dementia lacking distinct histopathological features.
AB  - Dementia lacking distinct histopathological features (DLDHF) belongs to the
      frontotemporal dementia syndromes. Behavioral, cognitive and motor symptoms are
      its usual clinical manifestations. However, considerable heterogeneity exists and
      no evident clinicopathological correlations can be performed. We report a patient
      who presented with a very unusual combination of behavioral abnormalities and
      prominent early parkinsonism progressing to a severe dementia. Pathological
      studies confirmed DLDHF with severe frontal and striatal neuronal loss and
      gliosis.

PMID- 16465770
TI  - Molecular analysis of chromosome 1, 10 and 19 abnormalities in human
      oligodendroglial tumors: relationship between frequency of LOH grade, age and
      gender.
AB  - BACKGROUND: Loss of heterozygosity (LOH) on 1p and 19q is observed in most
      oligodendroglial tumors. LOH on 10q appears to be less common in these tumors as
      compared to other gliomas. PATIENTS AND METHODS: We reviewed 14 patients with
      oligodendroglial tumors (10 low-grade and 4 anaplastic oligodendroglioma) to
      evaluate the frequency of LOH on 1p, 10q and 19q and correlate it with tumor
      grade and patients' age and gender; 5 loci on 1p and 5 on 19q as well as 4 on 10q
      were analyzed for LOH using PCR techniques. RESULTS: LOH on 1p together with 19q
      was detected in 6 tumors, 1 tumor showed deletion of 19q accompanied with
      deletion on 10q. Deletion on 1p was associated with deletion of 19q (p < 0.005)
      and mutual associations among deletions at loci on 19q (p < 0.05) were found.
      Patients with LOH on 1p were younger on average than patients with retained
      heterozygosity (p = 0.05). Grade II oligodendrogliomas predominated among younger
      patients (p < 0.01) while grade III oligodendrogliomas predominated among women
      (p < 0.005). No association between LOH on 1p nor 19q and tumor grade or
      patients' gender was found. CONCLUSION: Our study provides several clinically
      interesting findings and further supports the hypothesis of chromosome 1p and 19q
      involvement in the oligodendroglial cancerogenesis.

PMID- 16465771
TI  - Ciliated craniopharyngioma may arise from Rathke cleft cyst.
AB  - OBJECTIVE: The histogenesis of craniopharyngioma is not fully understood. We
      encountered a ciliated craniopharyngioma, the details of which may shed light on
      the histogeny of craniopharyngioma in general. PATIENT: A 74-year-old man
      presented with visual disturbance. Computed tomography showed an intra
      suprasellar cyst including a solid tumor. Transsphenoidal surgery was performed.
      During surgery, the cyst was found to contain mucoid milky-white fluid and a
      solid tumor 1 cm in diameter. Histologically, the tumor was shown to be a
      papillary type craniopharyngioma with foci of ciliated columnar epithelial cells.
      Ciliated craniopharyngioma was diagnosed. CONCLUSION: Our findings in this case
      together with findings in other reported cases suggest that the basal cells of
      Rathke cleft cyst transform to papillary type craniopharyngioma after squamous
      metaplasia, explaining the presence of the cilia and goblet cells.

PMID- 16465772
TI  - Malignant lymphoma of the central nervous system: difficult histologic diagnosis
      after glucocorticoid therapy prior to biopsy.
AB  - Four cases of central nervous system (CNS) lymphoma are reported which presented
      obstacles in diagnosis due to steroid treatment prior to biopsy. Reliable
      diagnoses were provided by molecular analysis. Malignant lymphoma of the CNS may
      be indistinguishable from other conditions, even in view of the gravity of the
      diagnosis. All patients had a previous history of glucocorticoid injection, for 2
      18 days prior to stereotactic brain biopsy. The pathologic examination revealed
      in all cases axonal destruction and reactive gliosis with a variable infiltration
      of B- or T lymphocytes and macrophages. Characteristically, scattered
      degenerating small round cells with pyknotic or fragmented nuclei were also
      observed. However, the molecular assessment of paraffin-embedded tissues revealed
      the monoclonal IgH gene rearrangement, which allowed the confident diagnosis of B
      cell lymphoma. The histopathological findings of the present cases suggest that
      the tumor cells might be selectively destroyed by steroid treatment, which may
      render diagnosis impossible. Thus, molecular genetic investigation constitutes an
      important tool for establishing a diagnosis of CNS lymphoma obscured by steroid
      administration. This is especially true in cases where a paucity of tumor cells
      is observed or when monoclonality fails to be demonstrated by immunohistochemical
      tests.

PMID- 16465773
TI  - Protein p62 common in invaginations in benign meningiomas--a possible predictor
      of malignancy.
AB  - OBJECTIVE: It is known that p62 is a cytosolic conserved protein that binds non
      covalently to ubiquitin. Expression of p62 has been seen in inclusions in
      neoplasias like hepatocellular and breast carcinomas but also in neuronal
      inclusions of degenerative brain disorders. Dysfunction of ubiquitin system leads
      to presence of p53 in cells suggested to be a predictor of future recurrence of
      meningioma. MATERIAL: The study material included 45 benign meningiomas of
      postmenopausal women operated in Kuopio University Hospital between 1994 and
      2002. METHODS: Patterns of p62 immunopositivity in meningiomas was evaluated and
      the results were correlated to clinical and histological parameters. RESULTS:
      Constant p62 labeling in at least each field measuring 1 mm in diameter was
      detected consisting of 5 different patterns. The most common labeling was seen in
      nuclear invaginations either as grains or homogenous labeling, followed by
      Marinesco like nuclear inclusions or rode like inclusions outside the
      invagination. In some cases cytoplasmic granular staining was seen. No
      correlation between different p62 patterns or extent of p62 expression,
      histological subtypes or proliferation marker Ki-67 was noted. CONCLUSION: Our
      results indicate that in the benign not recurrent meningiomas, signs of
      functioning proteosomal system, can be detected using the p62 labeling. The
      function of proteosomal system in malignant and specifically invasive meningiomas
      needs to be further elucidated.

PMID- 16465774
TI  - Extramedullary plasmacytoma extensively affecting the sella turcica and paranasal
      sinuses.
AB  - We report a 62-year-old Japanese male who complained of double vision and showed
      clear boundary mass extending to the clivus, intrasella, suprasella, ethmoidal
      sinus and sphenoid sinus on neuroimaging. The tumor mass was partially resected
      via transsphenoidal approach and was diagnosed as the extramedullary plasmacytoma
      by IgA immunostaining and electron microscopy. Making diagnosis from the imaging
      findings was difficult in this rare case, but immunohistological and electron
      microscopic examinations were useful for pathological diagnosis.

PMID- 16465775
TI  - Distribution of nuclear size and internuclear distance are important criteria for
      grading astrocytomas.
AB  - AIM: The differentiation between low-grade astrocytomas and anaplastic
      astrocytomas is susceptible to considerable inter-observer variability. In order
      to contribute to a better standardization of astrocytoma-grading based on
      quantitative data, the present study focuses on two important aspects not being
      considered in previous morphometric studies: elaboration of a decision flow chart
      for tumor grading based on morphometric parameters and appropriate cut-off
      values, easily performed using low-cost equipment such as measuring oculars;
      investigation of the distribution (histograms) of parameters describing nuclear
      size and internuclear distance, which had been represented in previous studies by
      their mean and standard deviation only. MATERIAL AND METHODS: At least 300 tumor
      cell nuclei per case were investigated in paraffin sections from surgical
      specimen of 75 patients with astrocytomas WHO grade II (n = 23) and anaplastic
      astrocytomas WHO grade III (n = 52) by means of a digital image analysis system.
      RESULTS: The morphometric data showed significant differences between both groups
      of tumors. According to multivariate analysis, the best contribution to tumor
      grading was achieved by means of parameters concerning the distribution of values
      for nuclear diameters and internuclear distances. A decision tree was constructed
      using a knowledge based algorithm, which provided astrocytoma grading based on
      the distribution of values for nuclear diameter, as well as the numerical nuclear
      density and proliferation index. Measurements using a measuring ocular took an
      acceptable amount of time (1.5 hour per case) and showed good reproducibility
      when compared with measurement by means of digital image analysis. CONCLUSION:
      The study demonstrates that a morphometric examination of tumor cell nuclei in
      paraffin sections supports the clinically important differential diagnosis
      between low-grade and high-grade astrocytomas. The method for classification and
      the data published in the present study constitute a good basis for a
      standardized and reproducible grading procedure for astrocytomas, which can be
      performed in any histologic laboratory even without a digital image analysis
      system.

PMID- 16465776
TI  - [The Ethics Committee meeting in Belgium May 7, 2004, on human experimentation].
AB  - The European directive 2001/20/EC concerning the performance or clinical trials
      has been transposed in the Belgian law of May 7, 2004, entitled "Loi relative aux
      experimentations sur la personne humaine" (Moniteur belge, May 18, 2004)". The
      range of the law is larger than those of the directive. Several new elements must
      be underlined: 1. Any experimentation on a human being may only begin if the
      promoter received a positive advice from an ethical committee according to the
      provision of the law. 2. For multicentric assays, a single opinion, identical for
      all the participating centres must be obtained. This implies a close dialogue
      between the ethical committees. A central committee is proposed by the industrial
      promoter. Each clinical trial of a drug must have a unique identification number
      obtained at the European agency for the evaluation of medicinal products (EMEA).
      3. Taking into account the fear of the pharmaceutical industry that some clinical
      studies could be "delocalized", the authorities accepted to reduce to twenty-
      eight days (instead of 60) the delay granted to the ethical committee in order to
      produce their single opinion. 4. The law of May 7, 2004, clearly defines the
      dispositions related to the protection of the participants. Particular
      dispositions are foreseen for the protection of minors, incapable adults and
      patients in emergency. 5. The promoter endorses, even without fault, the
      responsibility of the damage caused to the participant or his descendants. An
      insurance covering this risk must be contracted.

PMID- 16465777
TI  - [Role of matrix metalloproteinases in the endometrium in normal and pathologic
      menstruation].
AB  - Menstruation was thought to be the consequence of ischemic necrosis of the
      endometrium, resulting from vasoconstriction of the spiral arterioles. However, a
      new paradigm recently emerged when it was shown that human endometrium produces a
      lot of matrix metalloproteinases (MMPS) at menstruation. These MMPS are active
      and degrade almost all constituents of the extracellular matrix at neutral pH,
      allowing for tissue fragmentation and shedding. The tight control of their
      expression by progesterone and the close relationship in time and space between
      their expression and the lysis of the mucosa suggest their involvement in
      triggering menses as well as abnormal bleeding. A proof of their involvement was
      provided by culturing explants in conditions that mimic ex vivo the menstrual
      degradation of the endometrium, because specific inhibitors of MMPS prevent lysis
      of the extracellular matrix. Several cytokines have been shown to focally
      modulate the inhibition of MMPs expression by progesterone in a paracrine way.

PMID- 16465778
TI  - [Spontaneous ossification of the cervical spine after subtotal surgery
      spondylotic myelopathy].
AB  - Subtotal corporectomy without fusion (SCWF) is a misunderstood surgical procedure
      used in the treatment of spondylotic myelopathy. This clinical study was
      performed to evaluate the efficiency of the SCWF. Long term neurological status
      and cervical spine ossification were specially studied. Sixty-four patients,
      operated between 1990 and 2003, were evaluated. The average follow-up period was
      five years. To assess the severity of neurological symptoms, a functional seven
      point classification scale was used. Discriminant analysis was applied as
      statistic. There was a significant correlation between outcome, functional
      preoperative score, age, duration of the compression and intramedullary lesion in
      NMR. After SCWF, no secondary cervical instability was observed. Conversely, we
      show, for the first time in the literature, that on the twenty-one patients who
      were the subject of late 3D CT scan, there exists a true rebuilding of the
      cervical bone with spontaneous fusion and respect of cervical cord decompression.
      We conclude that the SCWF is a safe and efficient treatment for cervical
      spondylotic myelopathy. No fusion is required regardless of the number of levels,
      providing there is no preoperative instability. This surgical procedure which
      does not require any cervical immobilization considerably decreases surgical
      risks and costs imposed by the society.

PMID- 16465779
TI  - [Physiopathologic approach to symptoms and complication of anorexia nervosa:
      concerning various adipocytokines].
AB  - Anorexia nervosa (AN) is the most typical but also the most severe of eating
      disorders. Its prevalence among adolescents is estimated at 1% and its incidence
      has doubled the last twenty years. One of the most characteristic clinical sign
      in the anorexic people who have markedly decreased body mass index, is the
      prominent loss of fat tissues. This observation is confirmed by several studies
      of body composition measured by dual-energy x-ray absorptiometry or bioimpedance.
      The recent discovery of some adipocytokines, such as leptin and adiponectin has
      allowed to explain various complications classically described in AN, in
      particular hematologic changes, immunodepression, osteopenia and several neuro
      endocrine disorders.

PMID- 16465780
TI  - [Contribution to the study of mechanisms of rejection and tolerance in organ
      transplantation: minimizing immunosuppression as a strategy for graft tolerance
      in pediatric liver transplantation]].
AB  - Basic concepts in transplantation immunology have been recently revisited.
      Accordingly, the immune response towards an allograft is not anymore considered
      as necessarily harmful, but could participate, under certain conditions, to graft
      acceptation through active mechanisms. This novel paradigm was progressively
      evaluated in clinical liver transplantation, with the aim to minimize the
      immunosuppressive regimens and, as a first step, to completely withdraw steroids
      from the immunoprophylactic regimen. The development of laboratory tests to
      reproducibly assess the immune reactivity of a recipient towards his/her
      transplanted organ should allow the identification of operationally tolerant
      patients, and the elective withdrawal of maintenance immunosuppression in this
      subgroup.

PMID- 16465781
TI  - [New studies on the characterization of virulence factors in Microsporum canis].
AB  - Microsporum canis is a worldwide distributed zoophilic and zoonotic dermatophyte
      which is responsible for most cases of feline ringworm. Its prevalence is on the
      rise in developed countries. Since 1995, the author and his Laboratory have
      developed a research programme to better understand the pathogenesis of M. canis
      dermatophytosis. Both the potential fungal virulence factors and the host immune
      response were investigated. A 31.5 kDa keratinolytic subtilase (SUB) and a 43.5
      kDa keratinolytic metalloprotease (MEP) were purified from a crude exoantigen
      consisted in a mixture of inducible proteins secreted by the fungus in a medium
      enriched with keratin. Additionally, two gene families encoding respectively 3
      SUBs and 3 MEPs, including the 2 keratinases previously purified (called SUB3 and
      MEP3), were characterized. The genes encoding several MEPs and SUBs were shown to
      be transcribed in vivo during infection by nested RT-PCR. Finally, we
      demonstrated that a specific cellular immune response towards the crude
      exoantigen, MEP3 and SUB3 was induced in experimentally infected guinea pigs.
      This indicates that the potential immunoprotective properties of these antigens
      are interesting to evaluate in the frame of the development of an efficient
      vaccine against feline ringworm.

PMID- 16465782
TI  - [Differentiation, protection and regeneration of hair cells and auditory neurons
      in mammals].
AB  - Perception deafness, as opposed to transmission deafness, results from a lesion
      of the sensory cells and/or of the neurons of the auditory part of inner ear.
      There is currently no treatment able to stop the progression of a hearing loss or
      to restore a lost auditory function. We review here the progress which has been
      made with respect to the regeneration and the protection of neurosensory
      structures in the inner ear. A spontaneous post-lesional regeneration of hair
      cells in the sensory epithelium has been observed in amphibians and birds as well
      as in the vestibular part of the mammalian inner ear. In contrast, hair cells
      regeneration in the auditory portion of the inner ear of mammals appears to be
      limited to the developmental stages. The objective of this first part of our work
      is to try to identify progenitor cells in the cochlea and to characterize factors
      that are able to induce their proliferation and differentiation. Otoprotection of
      the sensory epithelium is another therapeutical strategy aimed at preventing
      further degradation of the auditory function. The prevention of the deleterious
      effect on hair cells of several drugs such as aminoglycosides and platin
      derivatives has been obtained using free radical scavengers or growth factors.
      Studies of the development of the innervation of the inner ear suggest the
      potential therapeutic interest of various growth factors, mostly the
      neurotrophins, to maintain the innervation of the adult Corti's organ.

PMID- 16465783
TI  - [Immunologic response to (pre)neoplastic cervical lesions associated with human
      papillomavirus].
AB  - Etiopathogenic and epidemiological studies have demonstrated that viruses are
      etiologically linked to approximately 20% of all human malignancies worldwide.
      Human papillomavirus (HPV) is one of the best characterized viruses associated
      with human cancer diseases, especially in the uterine cervix. Although the role
      of HPV is well established in the cellular transformation and maintenance of the
      malignant phenotype of keratinocytes, the viral infection by itself is not
      sufficient for cancer development. The small number of infected individuals
      eventually developing cancer of the cervix and the long latency period between
      primary infections and cancer emergence suggest that additional environmental or
      host factors are involved in malignant progression. In this context, the local
      mucosal immunity might be expected to play a key role in the host defence against
      HPV infection and associated-(pre)cancerous lesions. The purpose of this work was
      to analyse the immune co-factors implicated in the initiation and promotion of
      the neoplastic process. We have shown that the transformation zone (TZ), where a
      substantial majority of cervical (pre)cancers develop, is characterized by
      intrinsic immune alterations which could explain why this region is at higher
      risk of developing cancer. We have also provided evidence that the viral
      infection of cervical keratinocytes contributes to the local immunodeficiency by
      inhibiting the production of soluble and membrane molecules important for the
      migration and function of antigen-presenting cells.

PMID- 16465784
TI  - [Acute methanol intoxication: physiopathology, prognosis and treatment].
AB  - Acute methanol poisoning is still complicated by a poor vital or visual
      prognosis. The pathophysiology of methanol poisoning is not yet fully understood.
      It appears that the major toxic effects are related to the main metabolite of
      methanol, formic acid. The central nervous system and the visual pathway are the
      main targets of methanol poisoning. When irreversible brain lesions occur, the
      diagnosis of brain death can be made. Other organs, like the pancreas or the
      kidney, may also be damaged according to the severity of metabolic acidosis;
      however, the toxic manifestations are in this case mostly reversible. The
      historical treatment of methanol poisoning relies on ethanol administration.
      However, ethanol therapy has numerous side effects and a new antidote,
      fomepizole, that was previously approved for the treatment of ethylene glycol
      poisoning, appears effective, safe and easy to use. Hemodialysis remains
      effective for the removal of both methanol and formic acid.

PMID- 16465785
TI  - [Endocrine effects of environmental pollutants].
AB  - There is an increasing scientific concern that organochlorine compounds,
      recognized as environmental act through their estrogenic or anti-estrogenic
      properties. Many endocrine diseases can be concerned by the pathogenic role on
      environmental residues in their promotion. The carcinogenic potential of
      environmental xenoestrogens on breast cancer is a matter of controversy. In
      Europe, despite their prohibition since the 70's, residues persist in soil and
      rivers, resulting in a widespread contamination of the general population. Our
      results suggest that environmental exposure to p,p' -DDE, HCB or PCBs may
      contribute to multifactorial pathogenesis of breast cancer. Male infertility is
      also a matter of concern. Our data suggest that male infertility can be
      associated with exposure of the mothers to p,p'-DDE, and that deleterious effects
      are probably restricted to intra-uterine life. Early or precocious puberty in
      children adopted from developing countries where organochlorines are still used
      is frequently reported. A possible relationship with exposure to DDT is
      suggested. There are two possible pathways to account for precocious puberty
      following chronic exposure to estrogenic related compounds: weak stimulation of
      estrogen sensitive tissues or removal in Belgium of the suppressing effects of
      estrogens on gonadotrophins, suppressing effect that was due to exposure in the
      country of origin.

PMID- 16465786
TI  - [The solitude of Bartok: a hidden life].
AB  - The destiny of Bartok is closely related to that of his native land, Hungary. His
      life endured History's hazards and destiny's whims. It was a trip strewn with
      obstacles and marked by afflicting health problems; it went through boisterous
      conflicts and captivating passions, met the injuries of lack of understanding and
      the bruises of the unvoiced comment. This particular course opened the musician
      to the ethnomusicology and led him to the creation of original musical works. The
      exile towards the new world generated difficulties and creativity. An insidious
      disease mortgaged the future of this uprooted and, in several stages, led him to
      death. The periods of respite animated his creative genius and generated immortal
      works.

PMID- 16465787
TI  - [Ethics in general practice: between two dimensions, three poles and four times].

PMID- 16465788
TI  - [Disseminated lupus erythematosis: current therapies and future hopes].
AB  - The author summarizes his recent scientific achievements in the field of systemic
      lupus erythematosus, with special emphasis on the role of certain cytokines in
      the pathophysiology of the disease, the treatment of kidney involvement and
      glucocorticoid-induced bone manifestations.

PMID- 16465789
TI  - [Back from the centenial celebration].

PMID- 16465790
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Malaria--clinical aspects].

PMID- 16465791
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Urban malaria].

PMID- 16465792
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Malaria--therapeutic approaches].

PMID- 16465793
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Malaria control strategies].

PMID- 16465794
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Plasmodium vivax malaria].

PMID- 16465795
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Human African trypanosomiasis].

PMID- 16465796
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Chagas disease: renewed interest].

PMID- 16465797
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Leishmaniasis].

PMID- 16465798
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Severe acute toxoplasmosis in immunocompromised
      subjects: an outbreak in the Amazon?].

PMID- 16465799
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Bilharziasis caused by Schistosoma mekongi: an
      almost eradicated endemic disease].

PMID- 16465800
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Buruli ulcer].

PMID- 16465801
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Meningococcus meningitis].

PMID- 16465802
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Dengue fever].

PMID- 16465803
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Multisector approach to AIDS care].

PMID- 16465804
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Acceptability of vaccination programs in
      developing countries: sociocultural aspects].

PMID- 16465805
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. OPV versus IPV? Which vaccine is best to
      eradicate poliomyelitis?].

PMID- 16465806
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Tropical neurology].

PMID- 16465807
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Ophtalmology in the tropics].

PMID- 16465808
TI  - [Medecine and health in the Tropics. Rapid diagnosis tests used in tropical
      medicine].

PMID- 16465809
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. The tropical laboratory].

PMID- 16465810
TI  - [International conference on tropical medicine "Medicine and health in the
      Tropics" September 11 to 15 2005. Snakebite].

PMID- 16465811
TI  - [The Pharo at 100 years].

PMID- 16465812
TI  - [West Nile virus infection: serological investigation among horses in France and
      in Africa].
AB  - This study was carried out in 2003 to detected serological evidence of West Nile
      virus infection in 190 Army horses kept nearby French troops stationed in
      Southeast France and in Africa (Chad, Cote d'Ivoire and Senegal). Both IgG and
      IgM antibodies were searched for using an ELISA assay. Specifiity of IgG
      antibodies was determined by western blot and plaque reduction seroneutraization.
      Finding showed that 79% of the Army horses (n=96) tested in Africa presented
      specific IgG antibodies. All horses that were seropositive for IgG were
      seronegative for IgM. None of the Army horses (n=94) tested in the Southeast
      France were seropositive for West Nile virus. This study indicates that West Nile
      virus has circulated in all three African countries but not recently. It also
      underscores the value of western blotting as a rapid, specific confirmation
      technique that could eliminate the need to use plaque reduction
      seroneutralization.

PMID- 16465813
TI  - [Mycobacterium ulcerans disease (Buruli ulcer): surgical treatment of 102 cases
      in the Democratic Republic of Congo].
AB  - This report describes the preliminary results of surgical treatment of 102
      patients presenting Buruli ulcer (BU) over the 5-year period from January 1, 2000
      to January 1, 2005. The overall purpose is to improve therapeutic management of
      BU in the Democratic Republic of Congo. The main disease features were the same
      as those described in the literature. Diffuse mixed ulcerative forms were the
      most common in the hospital and at the health care center. Infection by
      Mycobacterium ulcerans was confirmed by microbacteriological analysis and
      histological study. Surgical removal of the BU was performed with primary suture,
      protective dressing, or skin grafting. Local care consisted of application of an
      aqueous solution of chloramine-metronidazole-nitrofurandoine daily after
      debridement. Skin grafting was performed with or without protective dressing.
      Preliminary results with a follow-up of 12 months showed healing in 62 cases,
      recurrece in 22, and unknown outcome in 18. Although surgical treatment was
      feasible in poor rural facilities, the cost depending on clinical form is high
      and recurrence is frequent. These findings undersscore the importance of early
      detection and treatment with antimycobacterials.

PMID- 16465814
TI  - [Value of computer tomography in the managment of brain injuries].
AB  - The purpose of this prospective study conducted from January 2001 to December
      2001 was to ascertain the value of computer tomography for evaluation of brain
      injuries. Computer tomography was performed using a Toshiba X VID system with
      contiguous 5 mm axial sections through the posterior fossa and 10 mm contiguous
      axial sections through the subtentorial region without contrast injection. A
      total of 107 patients with brain injuries were enrolled over the one-year study
      period. These patients accounted for 0.8% of all admissions to surgical emergency
      unit of Gabriel Toure Hospital in Bamako, Mali. The predominant age group for
      brain injuries was the 20- to 29-year-old group (35 cases). The male-to-female
      sex ratio was 5:1. Vehicular accident was the most frequent cause of brain injury
      (76 cases). Trauma was severe in 48 patients with a Glasgow score less than 8.
      Coma occurred immediately after injury in 90 cases. Ventricular hemorrhage led to
      coma in 100% of cases whereas brain hemorrhage and hematoma led to coma in 93.3%
      and 83.3% of cases respectively. Treatment was medical in 99 cases and
      neurosurgical in 8. The mortality rate was 34% and the morbidity rate (permanent
      sequels) was 36%. Computer tomography is a valuable tool for therapeutic decision
      making in medico-surgical emergencies involving brain injuries.

PMID- 16465815
TI  - [Epidemiological aspects of stroke in CT-scan department of the Point-G Hospital
      in Bamako, Mali].
AB  - The purpose of this prospective study conducted between January 2000 and December
      2001 was to identify tomodensitometric aspects of stroke. The relationship
      between lesion type (hemorrhagic, ischemic, and transient ischemic) and prognosis
      was assessed. Axial sections were made through the posterior fossa (5 mm at 5mm
      intervals) and subtentorial region (10 mm at 10 mm intervals). The Virchow plan
      was used as the reference for sections. The chi square test was used to evaluate
      the correlation between lesion type and prognosis. A total of 159 stroke patients
      with a mean age of 44.5 years were enrolled during the study period. There were
      90 men (56.6%) and 69 women (43.3%). In 118 patients (74.2%), CT scans showed
      cerebral abnormalities including ischemic lesions in 71 (44.6%) and hemorrhagic
      lesions in 47 (29.6%). Overall mortality was 45.7% (54/118). Hemorrhagic lesions
      were fatal in 51.1% (24/47) of cases and ischemic lesions in 35.2% (25/71).
      Transitory ischemic accidents were fatal in 0.12% of cases (5/41). This study
      demonstrates that CT scan is an important tool for stroke management by
      identifying the type and location of lesions.

PMID- 16465816
TI  - [Evaluation of the cost of stroke management in Dakar, Senegal].
AB  - The purpose of this one-year cross-sectional study conducted in 1997 was to
      estimate the direct cost of stroke management in the Neurology Department of Fann
      University Hospital in Dakar, Senegal. Data were collected about the type of care
      services required and related spending. Cost analysis was made in CFA Francs
      (CFAF), the Senegalese currency (1 USD = 500 CFAF in 1997). A total of 1260
      patients were hospitalized in the department including 383 for stroke (30.4%).
      Mean age was 60.8 +/- 14.2 years and men accounted for 49.2% of the population.
      The mortality rate was 46.2% among hospitalized patients. A total of 33,573
      medical acts were carried out including 12,052 (35.9%) for stroke management. The
      direct cost of stroke management was 32,614,442 CFAF with a mean cost of 78,426
      CFAF per patient. The cost was 18,839 CFAF in the patient care unit (57.8%) and
      4,954,635 CFAF in the neuroradiology unit (15.2%). The cost of health care
      personnel was 19,373,172 CFAF (59.4%) and the cost for drugs and other medical
      products was 8,253,246 CFAF. Health education programs aimed at increasing
      awareness of risk factors are needed to reduce the cost of stroke management in
      this difficult economic period.

PMID- 16465817
TI  - [Assessment of visual disability among 5 year-olds in Mayotte. A prospective
      study of 2849 schoolchildren in 2000].
AB  - To gain first insight into the prevalence of visual disability among children in
      Mayotte, a comprehensive study was undertaken in 2000 to determine the prevalence
      of impaired visual acuity, color blindness, ocular malformation, and oculomotor
      disturbance in five-year olds, second-year nursery schoolchildren. After
      preliminary assessment at school, children with serious visual impairment were
      referred for further examination by an ophthalmologist. Data was used to assess
      the number of visually impaired children in comparison with epidemiological data
      from metropolitan France and other countries as well as to estimate health care
      requirements in terms of the number of visual disabilities to be treated, glasses
      to be prescribed and rehabilitative and support programs to be set up. This study
      was novel not only for Mayotte but also for France because of the homogeneity of
      the population in terms of both age and geography. Results showed that children
      in Mayotte presented the same spectrum of eye disease as children elsewhere in
      the world. The prevalence of serious visual impairment was generally the same
      among 5-year-olds living in Mayotte as among their counterparts living in
      metropolitan France and English-speaking countries. However refractive visual
      disability was three times lower than among children in higher age brackets in
      metropolitan France.

PMID- 16465818
TI  - [Cataract in Burkina Faso: factors of choice between modern and traditional
      surgical procedures].
AB  - Despite advances in cataract surgery, many peoples in the Sub-Saharan region are
      still treated by the traditional lens couching technique. The purpose of this
      study is to investigate the factors leading to the choice of lens couching for
      cataract treatment. A total 34 patients (40 eyes) from the northern Burkina Faso
      who underwent lens couching were examined and interviewed. Most patients (56%)
      did not understand the etiology of cataracts and attributed the disease to fate.
      Nor did they know of any other cataract treatment than lens couching. Only 13
      patients (38.2%) would recommend modern cataract treatment and 52% suggested that
      health workers should come out into the villages and operate as traditional
      healers do. In spite of its potentially dramatic complications, lens couching is
      still the only method of cataract treatment known in some communities of Burkina
      Faso. Public information campaigns are needed to put an end to the ancestral
      practice of lens couching.

PMID- 16465819
TI  - [Congenital malaria as a result of Plasmodium malariae in an infant born to a HIV
      seropositive woman].
AB  - Congenital malaria is uncommon in France. The purpose of this report is to
      describe a case involving a six-week-old infant who was hospitalized with fever,
      hepatosplenomegaly, anemia and thrombopenia. Thick and thin blood smears were
      positive for Plasmodium malariae. The infant responded favorably to chloroquine.
      Based on this experience, we performed a search of the literature to find case
      reports on congenital malaria in France and compare clinical and epidemiologic
      data with series reported in the United States and from endemic areas. The
      placenta appears to provide an effective barrier against Plasmodium since
      infection is much more common than disease. The delay for onset of clinical
      symptoms is longer in temperate zones than in endemic areas. The type of parasite
      could account for this difference since African congenital malaria are due to
      Plasmodium falciparum while most cases described in the United States are due to
      Plasmodium vivax. We also discuss the possible implications of coinfection by HIV
      in the mother.

PMID- 16465820
TI  - [Dermatophytic disease in a Tunisian family].
AB  - Dermatophytic disease is a rare chronic infection caused by common dermatophytes
      and characterized by cutaneous and subcutaneous invasion. It is observed mainly
      in North Africa where it is presumably inherited via an autosomal recessive
      trait. Cellular immunodeficiency could account for the chronic nature of the
      disease and for its refractoriness to drug treatment. The purpose of this report
      is to describe the occurrence of dermatophytic disease in three sisters of
      consanguineous parents in a rural region of northern Tunisia. To our knowledge,
      this is the first familial case reported in Tunisia. The most salient features in
      these patients were early age of disease onset in three females, isolation of
      Microsporum canis at the beginning of the disease, relatively favorable course
      with long remissions in two cases, and absence of visceral involvement. Various
      drugs including antifungal agents and immunostimulants were used for treatment
      with disappointing results. Surgical excision associated with antifungal agents
      appeared to be effective in our patients. Dermatophytic disease remains a severe
      disease due to the possibility of potentially life-threatening visceral
      involvement.

PMID- 16465821
TI  - [Management of cutaneous leishmaniasis in adults and children].
AB  - Cutaneous leishmaniasis can present a variety of clinical features and courses.
      The causative Leishmania species is an important prognostic factor in
      immunocompetent patients. Local treatment modalities including topical
      paromomycin, cryotherapy, localized controlled heat, carbon dioxide laser
      therapy, or intralesional meglumine antimoniate can be effective against
      Leishmania major or Leishmania tropica. Oral fluconazole may be a second-line
      treatment. Parenteral antimonials are useful for persistent or recurrent Old
      World leishmaniasis. For New World leishmaniasis, parenteral antimonials
      represent the first-line treatment in all forms except those caused by Leishmania
      guyanensis in which pentamidine is preferable. Liposomal amphotericin B appears
      to be effective for treatment of cutaneous leishmaniasis but further study will
      be needed. Results using oral Miltefosine are promising against Indian kala-azar
      (Leishmania donovani) but disappointing against South American leishmaniasis.

PMID- 16465822
TI  - [Association of pulmonary tuberculosis and human immunodeficency virus infection
      (HIV) infection in Ouagadougou, Burkina Faso: diagnositic features, laboratory
      findings and statistical data].

PMID- 16465823
TI  - [Role of traditional healers at a health care outpost in Senegal].

PMID- 16465824
TI  - [Primary cervical choriocarcinoma of the uterine cervix].

PMID- 16465825
TI  - The debate over leprosy elimination versus sustainability of leprosy services.

PMID- 16465826
TI  - Flexor digitorum superficialis--revisited.
AB  - Flexor digitorum superficialis (FDS) is a median nerve innervated forearm muscle,
      and is usually available for transfer in palsied hands because of leprosy. Middle
      and ring finger FDS tendons have been preferably used in these procedures. The
      removal of FDS from fingers, to be used as motor elsewhere, has its own
      advantages and disadvantages. Many people think of FDS as four, more or less
      independent, muscles that may lead to problems when these tendons are used for
      non-synergistic transfers. Central to FDS muscle mass in forearm is a large flat
      common tendon that connects a single proximal muscle belly to two or three
      separate distal muscles, thus forming a complex digastric muscle. The muscle to
      middle finger tendon is totally independent. The anatomy of FDS muscle,
      functional capabilities of FDS tendons in different fingers, and the effects of
      removal of tendon from fingers have been discussed in the present article.

PMID- 16465827
TI  - Primary involvement of penile skin in lepromatous leprosy.
AB  - Skin lesions in lepromatous leprosy (LL) are usually multiple and widespread.
      Though the lesion may occur anywhere on the skin, male genitalia is rarely
      involved. In all cases reported so far about penile lesions of LL, there were
      lesions on the other parts of the body also. In some of the cases scrotum was
      also involved. We report here a patient who presented himself with a single
      macular lesion of leprosy on the shaft of his penis diagnosed as a case of
      lepromatous leprosy on slit-skin smear and histopathological examinations.

PMID- 16465828
TI  - Molecular detection of a virus, Pilchard herpesvirus, associated with epizootics
      in Australasian pilchards Sardinops sagax neopilchardus.
AB  - In 1995, and again in 1998, high mortalities of pilchards Sardinops sagax
      neopilchardus were seen over their entire geographical range on the Australian
      coastline. A virus with typical herpesvirus morphology was identified as the
      causative agent, although the source of the virus remains unknown. At the time of
      the mortality events, the only available diagnostic test available for the
      detection of the virus was electron microscopy and hence, development of a rapid
      diagnostic test for detection and identification of the virus was required.
      Initial sequence data for Pilchard herpesvirus (PHV) was acquired by comparing
      the highly conserved region of the ORF 62 gene of other piscine herpesviruses
      (Ictalurid herpesvirus 1 [Channel catfish virus, CCV] and Salmonid herpesvirus 2
      [Oncorhynchus masou virus, SaHV2, OMV]), and designing primers that successfully
      amplified a fragment of PHV. Here we describe the use of polymerase chain
      reaction (PCR) technology to detect PHV in infected tissues. Sequence analysis of
      amplified fragment resulting from this PCR is different from all known
      herpesviruses and can therefore distinguish PHV from all known viruses.

PMID- 16465829
TI  - Viral encephalopathy and retinopathy (VER) in Atlantic salmon Salmo salar after
      intraperitoneal challenge with a nodavirus from Atlantic halibut Hippoglossus
      hippoglossus.
AB  - Homogenate of tissue from juveniles of Atlantic halibut Hippoglossus hippoglossus
      suffering from viral encephalopathy and retinopathy (VER) was used to challenge
      smolt of Atlantic salmon Salmo salar with an initial average weight of 110 g. The
      nodavirus was administered in the form of an intraperitoneal injection, and the
      fish were kept for 134 d post challenge. Genotype characterisation of the
      nodavirus was performed by sequencing the RNA1 and RNA2 segments, and a
      quantitative real-time PCR (Q-PCR) assay was developed. Tissues from different
      organs were stained by immunohistochemistry (IHC). Samples were collected at
      random on Days 7, 25, 45, 69, 125 and 134 after challenge. Mortality, clinical
      signs and pathology of VER were observed only in the challenged group. The Q-PCR
      detected positive fish only in the challenged group, all of which were positive
      on all days of sampling. An increase in relative virus concentrations was
      observed from Day 7 to Day 25 post challenge. The increased level of virus
      concentration was maintained in the medulla oblongata throughout the experiment,
      suggesting persistence or slow elimination of the virus over time. The IHC
      detected positive cells on Days 34, 70 and 74. These results suggest that the
      nodavirus is transported to the medulla oblongata from the intraperitoneal
      injection site and is able to replicate in salmon. When injected, this nodavirus
      isolate caused mortality and established a persistent infection in the challenged
      salmon throughout the experiment. This susceptibility suggests that co-location
      of salmon and marine species should be avoided until further studies of possible
      transmission have been carried out.

PMID- 16465830
TI  - Histological, serological and virulence studies on rainbow trout experimentally
      infected with recombinant infectious hematopoietic necrosis viruses.
AB  - Several recombinant infectious hematopoietic necrosis viruses (IHNV) were
      produced by reverse genetics and their pathogenicity in trout was evaluated and
      compared to that of the wild type (wt) viruses IHNV and viral haemorrhagic
      septicemia virus (VHSV). Recombinant IHNVs used in this study were: rIHNV,
      identical to the wtIHNV; rIHNV-Gvhsv, a recombinant virus expressing the VHSV G
      gene instead of the IHNV G gene; rIHNV-Gmut, which possesses 2 targeted mutations
      in the glycoprotein; and rIHNVmut-Gmut, which is similar to the rIHNV-Gmut, but
      exhibits additional mutations along the genome. Results obtained in experimental
      infections showed that the rIHNV and rIHNV-Gmut were the most virulent
      recombinant viruses. Severity of the lesions induced by the different recombinant
      viruses was in agreement with mortality data. The kidney and the liver were the
      organs most affected by the most pathogenic viruses, and the lesions observed
      resembled those produced by wtIHNV. The introduction of mutations did not alter
      the tissue tropism of the virus. The recombinant viruses were able to replicate
      in fish, as shown by immunoperoxidase assay and RT-PCR. Antibodies against IHNV
      were detected in the fish inoculated with IHNV, rIHNV, rIHNV-Gmut and rIHNVmut
      Gmut, and antibodies against VHSV were also found in fish infected with rIHNV
      Gvhsv. Finally, antibody production was highest in fish infected with the
      rIHNVmut-Gmut even though this virus was the least virulent.

PMID- 16465831
TI  - Identification of the major outer membrane proteins of Aeromonas salmonicida.
AB  - Aeromonas salmonicida subsp. salmonicida is a Gram-negative bacterium that is the
      etiological agent of furunculosis, a serious infectious disease of salmonids.
      Aeromonas spp. are ubiquitous waterborne bacteria responsible for a wide spectrum
      of diseases among aquatic organisms and humans. Bacterial outer membrane proteins
      (OMPs) play a significant role in virulence as they comprise the outermost
      surface in contact with host cells and immune defense factors. To identify the
      major OMPs of A. salmonicida a proteomic analysis was undertaken using a
      carbonate OMP-enrichment protocol. The enriched OMP-extracts were separated by 2
      dimensional electrophoresis (2-DE) and the spots identified using liquid
      chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) via an electrospray
      ionization source. In total, 76 unique proteins were identified from the 125
      spots observed on the 2-D gel. The surface layer (S-layer) VapA protein dominated
      the A. salmonicida OMP 2-D profile, accounting for 60% of the protein on the 2-D
      gels. Among the other outer membrane proteins identified were at least 10 porins
      and various receptors involved in nutrient acquisition. Also identified in the
      carbonate insoluble fraction were phosphoglycerate kinase, enolase and others
      that lacked classical export sorting signals. The putative association of these
      proteins with the cell surface might provide new insights concerning the
      biological and pathogenic roles of these molecules in A. salmonicida infection.
      This work represents the first systematic attempt to characterize the cell
      surface of A. salmonicida.

PMID- 16465832
TI  - A marine bacterium, Micrococcus MCCB 104, antagonistic to vibrios in prawn larval
      rearing systems.
AB  - A marine bacterium, Micrococcus MCCB 104, isolated from hatchery water,
      demonstrated extracellular antagonistic properties against Vibrio alginolyticus,
      V. parahaemolyticus, V. vulnificus, V. fluviallis, V. nereis, V. proteolyticus,
      V. mediterranei, V cholerae and Aeromonas sp., bacteria associated with
      Macrobrachium rosenbergii larval rearing systems. The isolate inhibited the
      growth of V. alginolyticus during co-culture. The antagonistic component of the
      extracellular product was heat-stable and insensitive to proteases, lipase,
      catalase and alpha-amylase. Micrococcus MCCB 104 was demonstrated to be non
      pathogenic to M. rosenbergii larvae.

PMID- 16465833
TI  - Virulence of the amphibian chytrid fungus Batrachochytium dendrobatidis varies
      with the strain.
AB  - Although mortality in 3 groups of 15 green tree frogs Litoria caerulea exposed to
      3 isolates of Batrachochytrium dendrobatidis was 100%, time to death varied with
      isolate, highlighting the importance of strain and/or passage history in
      pathogenicity studies and possibly in the epidemiology of chytridiomycosis. A
      standard naming scheme for isolates of B. dendrobatidis is proposed.

PMID- 16465834
TI  - Life cycle stages of the amphibian chytrid Batrachochytrium dendrobatidis.
AB  - An overview of the morphology and life cycle of Batrachochytrium dendrobatidis,
      the cause of chytridiomycosis of amphibians, is presented. We used a range of
      methods to examine stages of the life cycle in culture and in frog skin, and to
      assess ultrastructural pathology in the skin of 2 frogs. Methods included light
      microscopy, transmission electron microscopy with conventional methods as well as
      high pressure freezing and freeze substitution, and scanning electron microscopy
      with critical point drying as well as examination of bulk-frozen and freeze
      fractured material. Although chytridiomycosis is an emerging disease, B.
      dendrobatidis has adaptations that suggest it has long been evolved to live
      within cells in the dynamic tissue of the stratified epidermis. Sporangia
      developed at a rate that coincided with the maturation of the cell, and fungal
      discharge tubes usually opened onto the distal surface of epidermal cells of the
      stratum corneum. A zone of condensed, fibrillar, host cytoplasm surrounded some
      sporangia. Hyperkeratosis may be due to (1) a hyperplastic response that leads to
      an increased turnover of epidermal cells, and (2) premature keratinization and
      death of infected cells.

PMID- 16465835
TI  - Distribution of Batrachochytrium dendrobatidis and pathology in the skin of green
      tree frogs Litoria caerulea with severe chytridiomycosis.
AB  - Although histopathology is used routinely for diagnosis of chytridiomycosis in
      live and dead amphibians, there are no quantitative data on the distribution of
      the causative fungus, Batrachochytrium dendrobatidis, in the skin. We performed
      quantitative histological examinations on 6 sites on the body and 4 toes of 10
      free-ranging adult green tree frogs Litoria caerulea found recently dead or dying
      from chytridiomycosis. Large numbers of sporangia occurred in all areas of
      ventral skin and toes; on average there were 94.3 sporangia mm(-1) of superficial
      epidermis. The number of sporangia was highly variable and this appeared to be
      related to the stage in the cycle of sloughing. The stratum corneum tends to
      build up with high intensities of infection and then sheds entirely rather than
      being shed continuously. Very few or no sporangia occurred on dorsal skin. This
      distribution could be explained by the dryness of the dorsal skin or possibly by
      the greater number of serous glands, which produce antifungal peptides, on the
      dorsum. In some frogs, ulceration and erosions occurred on skin on the back in
      the absence of sporangia. Other pathological changes such as hyperkeratosis and
      congestion occurred much more frequently on ventral surfaces.

PMID- 16465836
TI  - Skin lesions on North Atlantic right whales: categories, prevalence and change in
      occurrence in the 1990s.
AB  - North Atlantic right whales Eubalaena glacialis experienced decreased
      reproduction and body condition in the 1990s, causing concern about the overall
      health of this critically endangered population. Images from a detailed photo
      identification catalog of right whales were analyzed for the presence of skin
      lesions. Lesions were categorized as white lesions or blister lesions and each of
      those categories were further divided based on lesion morphology and location. Of
      439 whales photo-analyzed between 1980 and 2002, white lesions were detected on
      227 ind. (51.7%) and blister lesions were found on 76 ind. (17.3%). The majority
      of white lesions (72.8%) were detected in the Bay of Fundy where their prevalence
      increased dramatically during the 1990s (peaking at 40 and 41% of all identified
      whales in 1997 and 1999, respectively). A correlation between whale density and
      white lesions in the Bay of Fundy suggested that this lesion type may have been
      the result of a contagious agent, though the data on mother/calf pairs did not
      indicate transmission from mother to calf. Blister lesions appeared at low levels
      throughout the population over the study period. Neither lesion category was more
      prevalent on males or females, nor were there any differences between adults and
      juveniles. One white lesion type appeared exclusively on whales that had been
      entangled, and whose subsequent survival was in most cases questionable. This is
      the first detailed analysis of skin lesions in this species. Only 1 tissue sample
      has been previously obtained from a lesion, and thus the histology and etiology
      of these lesions remain unknown. Further work is needed to explore the role of
      disease and environmental variables in lesion prevalence.

PMID- 16465838
TI  - MS-222 (tricaine methane sulfonate) does not kill the amphibian chytrid fungus
      Batrachochytrium dendrobatidis.
AB  - MS-222 (tricaine methane sulfonate) is an agent commonly used to anaesthetise or
      euthanize amphibians used in experiments. It is administered by immersing the
      animal to allow absorption through the skin. Chytridiomycosis is an important
      disease of amphibians and research involves experiments with live animals.
      Batrachochytrium dendrobatidis, the fungus which causes chytridiomycosis, is
      located in the skin and therefore the organism should come into contact with MS
      222 when it is used. B. dendrobatidis is a sensitive organism which could
      possibly be killed by MS-222. Hence, results of chytridiomycosis studies in which
      MS-222 is used could be unreliable. A concentration of 2 g l(-1) and an exposure
      duration of 1 h is at the high end of the range at which MS-222 would be most
      commonly used. Exposure to 2 g l(-1) MS-222 for 1 h does not kill B.
      dendrobatidis cultures, suggesting that MS-222 is safe to use in chytridiomycosis
      studies.

PMID- 16465837
TI  - Unchanged prevalence of shell disease in the edible crab Cancer pagurus four
      years after decommissioning of a sewage outfall at Langland Bay, UK.
AB  - Shell disease is a bacteria-associated degradative disease of the crustacean
      exoskeleton that leads to formation of extensive lesions in the cuticle with
      ultimate involvement of haemocoelic septicaemia. Field surveys of edible crabs
      Cancer pagurus from Langland Bay, Gower, UK, from February 1997 to March 1998 had
      revealed unusually high prevalence (ca. 55%) of this disease amongst the
      population, and it was suggested that one of the predisposing factors might have
      been the presence of raw sewage in this area. Since February 1999, a local raw
      sewage outfall affecting this area has been decommissioned, raising the
      possibility that the prevalence and severity of this disease could have become
      reduced as a result of the cessation of sewage exposure. Therefore, the aim of
      this study was to compare the prevalence and severity of shell disease in edible
      crabs from Langland Bay pre- and post-sewage discharge. The overall prevalence of
      shell disease from February 2003 to March 2004 was 59.2%, and in only 1 size
      class (80-99 mm carapace width, males) was the prevalence higher in 2003-04 than
      in 1997-98. In terms of severity, only smaller crabs (60-199 mm width) showed a
      significant reduction in 2003-04 compared with 1997-98. No changes were found in
      the severity of the disease in different regions of the exoskeleton of infected
      crabs between the 1997-98 survey and the present work. Overall, it is concluded
      that no significant changes in the occurrence of shell disease have resulted from
      the improvement in water quality (in terms of faecal pollution) at this site,
      suggesting that sewage pollution is probably not a major contributory factor to
      this disease.

PMID- 16465839
TI  - [Evidence provides a safer basis in health care--neither more nor less].

PMID- 16465840
TI  - [Thrombolysis-treated ST-segment elevation myocardial infarction. Clopidogrel
      administration should be a standard].

PMID- 16465841
TI  - [Better with lower LDL cholesterol! Aim at 2 mmol/l for secondary prevention].

PMID- 16465842
TI  - [Plant sterols in common food-stuffs reduce serum cholesterol].

PMID- 16465843
TI  - [Big differences when it comes to neonatal care at eight Swedish obstetric
      departments].

PMID- 16465844
TI  - [From primary health care to invasive intervention. The cardiovascular patient's
      way through the Swedish health care system].

PMID- 16465845
TI  - [The heart remembers...and if we remember that, unnecessary examinations can be
      avoided].

PMID- 16465846
TI  - [Internal-medical disease revealed by anesthesia. A case report shows the
      unmasking effect of general anesthesia].

PMID- 16465848
TI  - [The Palme murder, the Estonia shipwreck, the Anna Lindh murder, the tsunami
      disaster... What makes an event a national trauma?].

PMID- 16465847
TI  - [Lex Maria--fatal cases must be reported to the police!].

PMID- 16465849
TI  - [Sick in Sweden--healthy in Europe?].

PMID- 16465850
TI  - [Unfounded criticism against the Swedish Animal Welfare Agency].

PMID- 16465851
TI  - [Health care a high-risk industry--information now better than new studies].

PMID- 16465852
TI  - [We should prescribe such drugs we ourselves would like to be treated with].

PMID- 16465853
TI  - [About SSRI preparations].

PMID- 16465854
TI  - [Unnecessary to scare the patients].

PMID- 16465855
TI  - [What is a human being? Biological, biochemical and genetic definitions are not
      enough].

PMID- 16465857
TI  - [In Citation].

PMID- 16465856
TI  - ["Blood connects everyone" - a wonderful motto].

PMID- 16465858
TI  - [Scientific pharmacy and homeopathy].

PMID- 16465859
TI  - [Selective enzyme inhibitor instead of an "iron-triggered cluster bomb"].

PMID- 16465860
TI  - [Complex regulation of dopamine d2 receptors].

PMID- 16465861
TI  - [Isolation of an osaltamivir-resistant H5N1 variant].

PMID- 16465862
TI  - [The history of hemophilia treatment].

PMID- 16465863
TI  - [Blood coagulation and hemorrhagic diathesis].

PMID- 16465864
TI  - [Production of essential blood plasma preparations].

PMID- 16465865
TI  - [Recombinant blood coagulation factors].

PMID- 16465867
TI  - [Acquired inhibitor hemophilia].

PMID- 16465866
TI  - [Concepts in hemophilia treatment].

PMID- 16465868
TI  - [The use of coagulation factors in hemophilia treatment].

PMID- 16465869
TI  - [Wilate--the first VWF/FVIII of the second generation--newly introduced in
      Germany].

PMID- 16465870
TI  - [Antibodies--the "magic bullets"?].

PMID- 16465871
TI  - Risk assessment of heavy metal contaminated soil in the vicinity of a lead/zinc
      mine.
AB  - Heavy metal contamination of soils through anthropogenic activities is a
      widespread and serious problem confronting scientists and regulators throughout
      the world. In this study we investigated the distribution, chemical species and
      availability of lead, zinc, cadmium and copper in nine surface (0 to 20 cm) soils
      from near an abandoned lead/zinc mine tailings located in Shaoxing, Zhejiang,
      China. Total heavy metal contents ranged from 5271 to 16369 mg/kg for Pb, 387 to
      1221 mg/kg for Zn, 3.0 to 9.3 mg/kg for Cd and 65 to 206 mg/kg for Cu. In
      general, all heavy metals exceeded China National Standards for Soil
      Environmental Quality of Heavy Metals by a factor of 3-65 times. Comparison of
      the heavy metal concentrations (Pb, Zn, Cd and Cu) with clay content revealed a
      strongly significant relationship while significant relationship (P < 0.001) was
      also obtained between Cd + Zn and Pb + Cu. Solid phase speciation of the soils
      using Tessier procedure showed that the heavy metals were distributed in the
      order: residual > organically complexed-Fe-Mn oxides occluded > carbonate bound >
      exchangeable > water soluble. In the organic matter fraction, the ratio of Pb
      (29.1%) to its total concentration in the soils was higher than those of Zn
      (4.70%), Cd (3.16%) and Cu (9.50%). The percentages of the water soluble and the
      exchangeable fractions of Pb (1.80%) and Cd (2.74%) were markedly greater than
      those of Zn (0.10%) and Cu (0.15%), suggesting that Pb and Cd are relatively more
      mobile and hence more toxic in the contaminated soils. Strongly significant
      relationships between H2O-Pb, H2O-Zn and H2O-Cu, strong positive correlations
      between H2O-Pb, H2O-Zn, H2O-Cu and organic matter in soil were found. The content
      of H2O-Pb, H2O-Zn, H2O-Cu was negatively correlated with pH values. The similar
      negative relationships between pH values and exchangeable heavy metals were also
      recorded. It is suggested that increasing soil pH or liming the soil could
      decrease bioavailability of heavy metals in the soil.

PMID- 16465872
TI  - Photodegradation of nitroaromatic compounds in aqueous solutions in the UV/ H2O2
      process.
AB  - Photodegradation of nitrobenzene and nitrophenols in aqueous solutions by means
      of UV/H2O2 process was studied in the Rayox batch reactors. Three nitrophenol
      isomers were identified as main photoproducts in the irradiated NB aqueous
      solutions. The distribution of nitrophenol isomers follows the order p- > m- > o
      nitrophenol. Other intermediates detected include nitrohydroquinone,
      nitrocatechol, catechol, benzoquinone, phenol, nitrate/nitrite ions, formic acid,
      glyoxylic acid, maleic acid, oxalic acid and some aliphatic ketones and
      aldehydes. The degradation of nitrobenzene and nitrophenols at initial stages
      follows the first-order kinetics and the decay rate constants for
      nitrobenzene(NB) are around 10(-3)-10(-2) s(-1) and for nitrophenols are around
      10(-2) s(-1). The decomposition of H2O2 in the presence of NB and each
      nitrophenol isomers follows zero-order kinetics. The quantum yields at initial
      stages for NB decay were estimated around 0.30 to 0.36, and for NPs decay is
      around 0.31-0.54.

PMID- 16465873
TI  - Enhanced biological nutrients removal using an integrated oxidation ditch with
      vertical circle from wastewater by adding an anaerobic column.
AB  - Compared to conventional oxidation ditches, an integrated oxidation ditch with
      vertical circle (IODVC) has the characters of concise configuration, simple
      operation and maintenance, land saving and automatical sludge returning. By the
      utilization of vertical circulation, an aerobic zone and an anoxic zone can be
      unaffectedly formed in the IODVC. Therefore, COD and nitrogen can be efficiently
      removed. However, the removal efficiency of phosphorus was low in the IODVC. In
      the experiment described, a laboratory scale system to add an anaerobic column to
      the IODVC has been tested to investigate the removal of phosphorus from
      wastewater. The experimental results showed that the removal efficiency of TP
      with the anaerobic column was increased to 54.0% from 22.3% without the anaerobic
      column. After the acetic sodium was added into the influent as carbon sources,
      the mean TP removal efficency of 77.5% was obtained. At the same time, the mean
      removal efficiencies of COD, TN and NH3-N were 92.2%, 81.6% and 98.1%,
      respectively, at 12 h of HRT and 21-25 d of SRT. The optimal operational
      conditions in this study were as follows: recycle rate = 1.5-2.0, COD/TN > 6,
      COD/TP > 40, COD loading rate = 0.26-0.32 kgCOD/(kgSS x d), TN loading rate =
      0.028-0.034 kgTN/(kgSS x d) and TP loading rate = 0.003-0.005 kgTP/(kgSS x d),
      respectively.

PMID- 16465874
TI  - A 50-years record of dichloro-diphenyl-trichloroethanes and
      hexachlorocyclohexanes in lake sediments and penguin droppings on King George
      Island, Maritime Antarctic.
AB  - Since the ban on the use of organochlorine pesticides (OCPs) such as dichloro
      diphenyl-trichloroethane (DDT) and hexachlorocyclohexane(HCH) in agriculture,
      their levels have generally dropped. In a number of cases, however, the levels of
      these OCPs were found to be unchanging or even increasing after the ban. With the
      aim to unveil the possible causes of these exceptions, we collected two lake
      cores from King George Island, West Antarctica, and determined their accumulation
      flux profiles and temporal trends of these OCPs. In the lake core sediments with
      glacier meltwater input, the accumulation flux of DDT shows an abnormal peak
      around 1980s in addition to the expected one in 1960s. In the lake core sediments
      without glacier meltwater input, the accumulation flux of DDT shows a gradual
      decline trend after the peak in 1960s. This striking difference in the DDT flux
      profiles between the two lake cores is most likely caused by the regional climate
      warming and the resulted discharge of the DDT stored in the Antarctic ice cap
      into the lakes in the Antarctic glacier frontier. Furthermore, to investigate the
      change of OCPs loadings in the Antarctic coastal ecosystem, we reconstructed the
      HCH and DDT concentration profiles in penguin droppings and observed a gradual
      increase for the former and a continuous decrease for the latter during the past
      50 years. The increase of HCH seems to be due to the regional warming from the
      early 1970s and the resulted HCH discharge to the coastal ecosystem by glaciers'
      meltwater and the illegal use of HCH in the Southern Hemisphere in the recent
      decade. Thedifferent temporal trends of HCH and DDT accumulation rate in the lake
      core with glacier meltwater input and the aged penguin droppings can be explained
      by their different water-soluble property.

PMID- 16465875
TI  - Sedimentation of short cylindrical pollutants with mechanical contacts.
AB  - Lattice Boltzmann method and elastic particle collision model were used to
      investigate the sedimentation of short cylindrical pollutant particles with
      mechanical contacts for varying bulk number density epsilon and terminal Reynolds
      number ReT. The corresponding experiments were performed as a comparison. The
      clusters of pollutant particles with an inverted "T" structure were observed, the
      pollutant particles for high epsilon and large ReT scattered wider than that for
      low epsilon and small ReT. The sedimentation velocities increased suddenly at the
      initial stage, then decreased drastically, after that swayed around and
      approached to a steady value. The time to steady state did not depend on epsilon
      and ReT. The effect of particle interactions was to hinder the average
      sedimentation velocity, and hindrance was directly proportional to epsilon. The
      orientation distributions of pollutant particles depended on ReT and epsilon,
      especially on the former. Both the standard deviations of vertical and horizontal
      velocity, the former was larger than the latter, were nearly independent on
      epsilon and ReT.

PMID- 16465876
TI  - Size distribution of the secondary organic aerosol particles from the
      photooxidation of toluene.
AB  - In a smog chamber, the photooxidation of toluene was initiated by hydroxyl
      radical (OH*) under different experimental conditions. The size distribution of
      secondary organic aerosol(SOA) particles from the above reaction was measured
      using aerodynamic particle sizer spectrometer. It was found from our experimental
      results that the number of SOA particles increased with increasing the
      concentration of toluene. As the reaction time prolonged, the sum of SOA
      particles was also increased. After a reaction time of 130 min, the concentration
      of secondary organic aerosol particles would be kept constant at 2300
      particles/cm3. Increasing illumination power of blacklamps could significantly
      induce a higher concentration of secondary organic aerosol particle. The density
      of SOA particles would also be increased with increasing concentration of CH3
      ONO, however, it would be decreased as soon as the concentration of CH3 ONO was
      larger than 225.2 ppm. Nitrogen oxide with initial concentration higher than 30.1
      ppm was also found to have little effect on the formation of secondary organic
      aerosol.

PMID- 16465877
TI  - Relationship between light and heavy fractions of organic matter for several
      agricultural soils in China.
AB  - Although numerous studies about the nature and turnover of soil organic
      matter(SOM) in light and heavy fractions(LFOM and HFOM, respectively) have been
      made, little information is available in relation to the relationship between
      LFOM and HFOM, and no attempts have been made to quantify a general relationship
      between LFOM and HFOM for agricultural soils under field condition. Our
      hypothesis is there may be an inherent relationship between LFOM and HFOM for
      agricultural soils under certain unaltered management practices for a long
      period, to this end, we therefore studied typically soils taken from different
      parts in China by using a simple density fractionation procedure. The results
      indicated that LFOM was positively correlated with LFOM/HFOM ratio for three
      typical soils. This information will be of particular use not only in deepening
      our understanding of the dynamics of SOM fractions but also in evaluating the
      potential of agricultural soils to sequestrate C under different management
      practices in a long term.

PMID- 16465878
TI  - On-line optical determination of floc size of Fe(III) coagulants.
AB  - This study investigated the floc aggregation, average floc size, floc size
      variance and floc growth velocity when ferric chloride (FeCl3) and polyferric
      chloride (PFC) were used to treat the simulated water samples. The factors
      including coagulant dose, ionic strength and solution pH, which affect the floc
      aggregation, were studied. Experiments were carried out in a bench-scale reactor
      using photometric dispersion analyzer (PDA). Results showed that there were great
      differences between the floc aggregation of PFC and FeCl3. The average floc size
      and floc growth velocity of PFC were much larger than those of FeCl3. Compared
      with FeCl3, PFC gave a better coagulation performance in wider range of pH,
      dosage and ionic strength. It was also found that the coagulation efficiency of
      PFC did not depend on average floc size but on floc growth velocity.

PMID- 16465879
TI  - Mechanistic study of ozonation of p-nitrophenol in aqueous solution.
AB  - Ozonlysis in the treatment of p-nitrophenol solution was studied in this paper.
      The results indicated that the decomposition of p-nitrophenol was accelerated as
      the gas flow rate or pH value increased. When gaseous ozone concentration was
      20.11 mg/L and pH was 3, after 24 min reaction, the removal rate of p-nitrophenol
      reached 73.04%, 86.11%, 91.71% and 95% at the gas flow rate of 32, 40, 48 and 56
      ml/min respectively. And when pH was 3, 4, 5, 6, the decomposition rate was
      66.38%, 82.09%, 90.46%, 97.50% after a 20 min reaction respectively. It was
      mainly O3 molecule that took part in the decomposition when pH was 3. The main
      intermediates during the decomposition include catechol, o-benzoquinone,
      hydroquinone, p-benzoquinone, phenol, fumaric acid, maleic acid, oxalic acid and
      formic acid. The decomposition mechanism of p-nitrophenol was also discussed.

PMID- 16465880
TI  - A novel fiber coating for solid phase microextraction and its application for the
      extraction of n-alkane from aqueous sample.
AB  - Base on the previous work in laboratory, a novel polyaniline doped with
      polydimethylsiloxane coating was developed on a stainless steel wire for solid
      phase microextraction(SPME) by electroplating method. This electroplating method
      not only has advantages of ease preparation and simple equipments required, but
      also increases the lifetime of the SPME fiber. The composite fiber (polyaniline/
      polydimethylsiloxane(PANI/PDMS)) was evaluated by analyzing n-tridecane, n
      tetradecane and n-pentadecane in aqueous sample. The new fiber coating showed
      comprehensive abilities to extract alkanes compounds. The relative standard
      deviations were found to be 6.8%-10.33%.

PMID- 16465881
TI  - Degradation kinetics and products of triazophos in intertidal sediment.
AB  - This work presents laboratory studies on the degradation of triazophos in
      intertidal sediment. The overall degradations were found to follow the first
      order decay model. After being incubated for 6 d, the percentage of degradations
      of triazophos in unsterilized and sterilized sediments were 94.5% and 20.5%,
      respectively. Between the temperatures of 15 degrees C and 35 degrees C, the
      observed degradation rate constant (kobsd) enhanced as the incubation temperature
      increased. Triazophos in sediment degraded faster under aerobic condition than
      under anaerobic one. The water content of sediment had little influence on the
      degradation when it was in the range of 50%-100%. The values of kobsd decreased
      with increasing initial concentration of triazophos in sediment, which could
      result from the microorganism inhibition by triazophos. Four major degradation
      products, o, o-diethyl phosphorothioic acid, monoethyl phosphorothioic acid,
      phosphorothioic acid, and l-phenyl-3-hydroxy-1,2,4-triazole, were tentatively
      identified as their corresponding trimethylsilyl derivatives with a gas chromato
      graphy-mass spectrometer. The possible degradation pathway of triazophos in
      intertidal sediment was proposed. The results revealed that triazophos in
      intertidal sediment was relatively unstable and could be easily degraded.

PMID- 16465882
TI  - Influence of phosphorus on Microcystis growth and the changes of other
      environmental factors.
AB  - The growth processes of Microcystis aeruginosa (FACHB-41) in simulated Taihu Lake
      water with different phosphorus concentrations were investigated using laboratory
      microcosms. The algal biomass increased with the increase of phosphorus
      concentration when it was lower than 0.445 mg/L, while the dissolved oxygen (DO)
      and pH increased, dissolved inorganic nitrogen(DIN) and light intensity
      underwater (I) decreased. Responding to the changes of the "environmental
      factors", the cellular carbohydrate and its ratio to cellular protein decreased
      generally as phosphorus increased. However, when phosphorus concentration was
      higher than 1.645 mg/L, the biomass, the "environmental factors", the cellular
      carbohydrate and its ratio to cellular protein did not change likewise. Since the
      environmental factors and the physiological and biochemical responses are
      important factors, the change of environmental factors and cell physiology and
      biochemistry induced by phosphorus may become the key factors that steer the
      growth and dominance of Microcystis under certain conditions. To sum up,
      phosphorus not only stimulate the growth of Microcystis directly by supplying
      nutrient element, but also has complex interactions with other "environmental
      factors" and play important roles in the growth processes of Microcystis.

PMID- 16465883
TI  - Fulvic acid degradation using nanoparticle TiO2 in a submerged membrane
      photocatalysis reactor.
AB  - The degradation of fulvic acid (FA) by nanoparticle TiO2 in a submerged membrane
      photocatalysis (SMPC) reactor was studied. In this reactor, photocatalytic
      oxidation and membrane separation co-occured. The continuous air supplier
      provided O2 for the photocatalytical reaction and mixed the solution through an
      airflow controller. The particle TiO2 could automatically settle due to gravity
      without particle agglomeration so it could be easily separated by microfiltration
      (MF) membrane. It was efficient to maintain high flux of membranes. The effects
      of operational parameters on the photocatalytic oxidation rate of FA were
      investigated. Results indicated that photocatalyst at 0.5 g/L and airflow at 0.06
      m3/h were the optimum condition for the removal of fulvic acid, the removal
      efficiency was higher in acid media than that in alkaline media. The effects of
      different filtration duration on permeate flux rate of MF with P25 powder and
      with nanoparticle TiO2 were compared. Experimental results indicated that the
      permeate flux rate of MF was improved and the membrane fouling phenomenon was
      reduced with the addition of nanoparticle TiO2 catalyst compared with
      conventional P25 powder. Therefore, this submerged membrane photocatalysis
      reactor can faciliate potential application of photocatalytic oxidation process
      in drinking water treatment.

PMID- 16465884
TI  - Application of Bayesian regularized BP neural network model for analysis of
      aquatic ecological data-a case study of chlorophyll-a prediction in Nanzui water
      area of Dongting Lake.
AB  - Bayesian regularized BP neural network(BRBPNN) technique was applied in the
      chlorophyll-a prediction of Nanzui water area in Dongting Lake. Through BP
      network interpolation method, the input and output samples of the network were
      obtained. After the selection of input variables using stepwise/multiple linear
      regression method in SPSS 11.0 software, the BRBPNN model was established between
      chlorophyll-a and environmental parameters, biological parameters. The achieved
      optimal network structure was 3-11-1 with the correlation coefficients and the
      mean square errors for the training set and the test set as 0.999 and 0.00078426,
      0.981 and 0.0216 respectively. The sum of square weights between each input
      neuron and the hidden layer of optimal BRBPNN models of different structures
      indicated that the effect of individual input parameter on chlorophyll-a declined
      in the order of alga amount > secchi disc depth (SD) > electrical conductivity
      (EC). Additionally, it also demonstrated that the contributions of these three
      factors were the maximal for the change of chlorophyll-a concentration, total
      phosphorus (TP) and total nitrogen (TN) were the minimal. All the results showed
      that BRBPNN model was capable of automated regularization parameter selection and
      thus it may ensure the excellent generation ability and robustness. Thus, this
      study laid the foundation for the application of BRBPNN model in the analysis of
      aquatic ecological data(chlorophyll-a prediction) and the explanation about the
      effective eutrophication treatment measures for Nanzui water area in Dongting
      Lake.

PMID- 16465885
TI  - Fluorescence characteristic changes of dissolved organic matter during municipal
      solid waste composting.
AB  - Dissolved organic matter(DOM) of municipal solid waste (MSW) consists of
      minerals, water, ash and humic substances, and is known to enhance plant growth.
      In this study, inoculating microbes (ZJ, MS) were used in municipal solid wastes
      composting, and composting implemented a industrialized technology. During
      composting, dissolved organic matter was extracted from the compost and purified.
      The spectral characteristics of dissolved organic matter was determined by
      fluorescence emission, excitation, and synchronous spectroscopy. Fluorescence
      emission, excitation, and synchronous spectra characterized by different relative
      fluorescent intensities and peaks over time. Fluorescence spectra were similar to
      that of fulvic acid in sewage sludge, indicating the presence of dissolved
      organic matter with aromatic structures and a high degree of molecular
      polymerization. Compared with the controls with no microbial inoculation, the
      microbe-inoculated treatments exhibited the increase of aromatic
      polycondensation, in the following order: MS + ZJ > ZJ > MS > CK.

PMID- 16465886
TI  - Changes of Cu, Zn, and Cd speciation in sewage sludge during connposting.
AB  - The potential toxicity risks from heavy metals depend on their chemical
      speciation. The four stages of the Tessier sequential extraction method were
      employed to investigate changes in heavy metal speciation (Cu, Zn, and Cd) of
      sewage sludge during forced aeration composting, and then to identify whether the
      composting process would reduce or enhance their toxicities. Throughout the
      composting process, the exchangeable, carbonate-bound, Fe-Mn oxide-bound, and
      organic matter-bound fractions of Cu were converted to the residual Cu fraction.
      The organic matter-bound Cu fraction greatly contributed to this transformation.
      Residual Zn fraction was transformed to the Fe-Mn oxide-bound and organic matter
      bound fractions after composting. The residual Zn fraction was a major
      contributor to the organic matter-bound Zn fraction. The availability of Cu and
      Zn was reduced by composting such that the risk of heavy metal toxicity decreased
      with prolonged treatment times. Additionally, attention should be paid to the
      increased availability of Cd in sewage sludge after composting treatment.

PMID- 16465887
TI  - Sorption of pyrene on two paddy soils and their particle-size fractions.
AB  - In the present study, the sorption of pyrene on two kinds of bulk paddy soils,
      Gleyic Stagnic Anthrosols, and Ferric accumulic Stagnic Anthrosols as well as
      their particle-size fractions was investigated. The sorption isotherms fitted
      well with Freundlich equation. For both soils, the clay fraction( < 2 microm) and
      coarse sand fraction(2000-250 microm) had higher sorption capacity than fine sand
      fraction(250-20 microm) and silt fraction(20-2 microm). The log Koc values
      obtained of each soil and its particle-size fractions were similar, proving that
      SOM content was a key factor affecting pyrene sorption. The Kd values showed a
      significant correlation with contents of dithionite-extractable Fe in both paddy
      soils and a good relationship with CEC in Gleyic Stagnic Anthrosols, indicating
      possible effects of surface properties of particle-size fractions on the sorption
      of pyrene.

PMID- 16465888
TI  - Variation in photosynthetic photon flux density within a tropical seasonal rain
      forest of Xishuangbanna, south-western China.
AB  - The effects of canopy development, solar angle, and weather conditions on
      temporal variation in photosynthetic photon flux density(PPFD) at three heights
      within a tropical rain forest canopy in Xishuangbanna, China, were examined. PPFD
      was measured every second and stored as 10-min averages from 1 December 2002 to
      30 November 2003. PPFD variability was examined at three different temporal
      scales. Specific days in March, September, and December with clear and overcast
      sky conditions were selected to separate the effects of leaf area index (LAI) and
      solar angle on diurnal variability. On both clear and overcast days, mean daily
      average PPFD was significantly different between March and September at all
      heights, except 10 m on clear days, suggesting that LAI directly influences PPFD.
      In contrast, the differences in daily average PPFD among three heights between
      September and December were likely due to variation in solar angle. In addition,
      daily average PPFD at all locations were significantly lower under overcast than
      clear sky conditions in March, September and December. Over the year-long study,
      the mean daily total PPFD at 21 m, 10 m and 4 m was 2.8, 2.7 and 0.7 mol/(m2 x
      d), which accounted for 9.7%, 9.4% and 2.4% of the daily PPFD above the canopy,
      respectively. Significant differences in mean daily total PPFD occurred at the
      same heights among different seasons, and diurnal, day-to-day and seasonal PPFD
      varied at different heights within the canopy. The possible effects of light
      variability on physiological and morphological responses of plants are discussed.

PMID- 16465889
TI  - Effect of fertilizer and water content on N2O emission from three plantation
      soils in south China.
AB  - The effects of fertilizers and water content on N2O emission were studied using
      the three most typical plantation soils. Soil incubations were performed and
      fertilization and water content treatments were designed. At 25% of saturated
      water content(SWC), N2O emissions from the soil treated with urea, KNO3, (NH4)2
      SO4 and KH2 PO4 were compared at application rates of 0, 100, 200, 300 and 500
      kg/hm2. At 80% of SWC, similar experiments were carried out but at only one
      application rate(500 kg/hm2). N2O emissions at various water contents(20%, 35%,
      50%, 65%, 80% and 100% of SWC) were studied. At low water content(25% of SWC),
      neither nitrogen nor phosphorus(or potassium) fertilizers led to a high level of
      N2O emission, which generally ranged from 2.03 to 29.02 microg/(m2 x h). However,
      at high water content(80% SWC), the fertilizers resulted in much greater N2O
      emission irregardless of soil tested. The highest N2O emission rates after 24 h
      of water addition were 1233 microg/(m2 x h) for S. superba soil, 1507 microg/(m2
      x h) for P. elliottii soil and 1869 microg/ (m2 x h) for A. mangium soil
      respectively. N2O emission from soils treated with urea, (NH4)2 SO4 and KH2 PO4
      immediately dropped to a low level but steadily increased to a very high level
      for the soil treated with KNO3. High NO3- content was a basis of high level of
      N2O emission. N2O emission rates from soils peaked shortly after flooding,
      rapidly dropping to a very low level in soil from non-legume plantations, but
      lasting for a relatively long period in soil from legume plantations. When soil
      water content increased equaling to or higher than 65%, the accumulated N2O
      emission over a period of 13 d ranged from 20.21-29.78 mg/m2 for S. superba,
      30.57-70.12 mg/m2 for P. elliottii and 300.89-430.51 mg/m2 for A. mangium. The
      critical water content was 50% of SWC, above which a high level of N2O emission
      could be expected, and below which very little N2O emissions were detected. The
      results suggest that, at low water content (< 50% of SWC), the fertilization
      practice is safe with regard to N2O emissions, but at high water content (> 50%
      of SWC), nitrogen fertilizer in the form of nitrate could yield a 100-fold
      increase in N2O emissions. Legume plantations like A. mangium should be avoided
      in low lands which could easily suffer from flooding or poor drainage.

PMID- 16465890
TI  - Characteristics of PM2.5 in rural areas of southern Jiangsu Province, China.
AB  - To understand pollution level and possible sources of atmospheric fine
      particulates in rural areas of southern Jiangsu Province of China, samples of
      PM2.5 were collected and analyzed in Xueyan Town and Taihu Lake Station over
      three seasons from July 2002 to January 2003. The mass concentrations of PM2.5
      and 14 principal component elements were obtained. The results showed that
      pollution of PM2.5 was serious and the concentration levels of S, Zn, Pb and As
      were similar to city. There are different seasonal distribution laws of pollutant
      elements in PM2.5 between two sampling sites, probably due to contribution of
      local sources, medium or long distance transportation of fine particulates and
      complicated meteorological conditions. The enrichment levels of S, Zn, Pb, As, K
      were high, reflecting the influence of anthropogenic activities. Particularly
      enrichment level of S was much higher in summer, which was probably related to
      meteorological condition. The result of principal components analysis showed
      major sources of PM2.5 included crustal resuspension, coal burning, metal
      processing industry or waste incineration, vehicular emission, which suggests
      anthropogenic activities is of important influence on PM2.5 in rural areas of
      southern Jiangsu Province.

PMID- 16465891
TI  - Estimation of OCDD degradation rate in soil.
AB  - The current concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) were determined in soils contaminated with Chinese technical product
      sodium pentachlorophenate (Na-PCP). The estimated half-life of octachlorodioxin
      (OCDD) was about 14 years in contaminated soils based on the local historical
      record and mass balance calculation during the past 43 years (1960-2003). The
      isomer profiles remained the same regardless of paddy field soil or riverbank
      soil. The results indicated that the congener-specific information was efficient
      in estimating the PCDD/Fs fate in contaminated soils.

PMID- 16465892
TI  - Decolorization of azo dyes with high salt concentration by salt-tolerant mixed
      cultures under anaerobic conditions.
AB  - Because the lack of detailed study of biological decolorization in high salt dye
      wastewater, it is still difficult to evaluate the biological treatment on high
      salinity dye wastewater. The experiments were carried out to study the salt
      tolerant bacteria, which is useful in the treatment of high-salinity colored
      wastewater. Simulated wastewater containing 5-150 g/L salt (NaCl) and 50-2000
      mg/L Reactive Brilliant Red K-2BP was treated with three salt-tolerant mixed
      cultures (CAS, TAS, DSAS), which were under a gradually acclimated procedure.
      With the increase of concentrations of salt and dye, the decolorization became
      low. The abilities of decolorization of dyes wastewater by three mixed cultures
      (CAS, TAS, DSAS) were studied, CAS and DSAS mixed cultures showed more active for
      the treatment of high-salinity colored wastewater than TAS mixed cultures. The
      results suggested that there might be a simple process for the high salt
      wastewater treatment, which could be incorporated into conventional activated
      sludge plants.

PMID- 16465893
TI  - Determination of hemoglobin adduct of a musk xylene metabolite in trout as
      biomarker of exposure by gas chromatography mass spectrometry.
AB  - Musk xylene(MX) is frequently used as fragrances in formulation of personal care
      products. Quantification of a bound 4-amino-MX(4-AMX) as cysteine adducts in
      trout hemoglobin(Hb) was made by gas chromatography-ion trap-mass
      spectrometry(GC/MS). The Hb samples were collected from trout after 24 h exposure
      to MX at 10 microg/g, and or menhaden oil(control). The formation of cysteine-Hb
      adduct was observed from nitroso derivative of MX, released by alkaline
      hydrolysis. The released 4-AMX metabolite was extracted in n-hexane. The extract
      was then reduced by evaporation, and analyzed by GC/MS. When similar agreement of
      mass spectral features and retention time of 4-AMX were obtained in both standard
      and sample solutions, the presence of 4-AMX metabolite in the Hb was confirmed.
      The concentration of 4-AMX was found to be 3.1 x 10(-6)--6.9 x 10(-6) mg/g in the
      Hb solution. Quantitation was made based on an internal standard, a calibration
      plot, and response factor. In the non-hydrolyzed and laboratory blank extracts,
      the 4-AMX metabolite was not detected. Additionally, coeluting and interfering
      ions were observed in the biological samples.

PMID- 16465894
TI  - Distribution characteristics of ammonia-oxidizing bacteria in the Typha latifolia
      constructed wetlands using fluorescent in situ hybridization (FISH).
AB  - A molecular biology method, fluorescent in situ hybridization (FISH), in which
      the pre-treatment was improved in allusion to the media of the constructed
      wetlands (CW), e.g. the soil and the grit, was used to investigate the vertical
      distribution characteristics of ammonia-oxidizing bacteria (AOB) quantity and the
      relation with oxidation-reduction potential (ORP) in the Typha latifolia
      constructed wetlands under three different loadings in summer from May to
      September. Results showed that the quantity of the AOB decreased in the Typha
      latifolia CW with the increase of vertical depth. However, the AOB quantity was 2
      4 times the quantity of the control in the root area. Additionally, ORP in the
      rhizosphere was found to be higher than other areas, which showed that Typha
      latifolia CW was in an aerobic state in summer when using simulated non-point
      sewage at the rural area of Taihu Lake in China and small town combined sewage.

PMID- 16465895
TI  - Adsorption of dyes onto activated carbon prepared from olive stones.
AB  - Activated carbon was produced from olive stones(OSAC) by a physical process in
      two steps. The adsorption character of this activated carbon was tested on three
      colour dyes molecules in aqueous solution: Methylene blue (MB), Rhodamine B (RB)
      and Congo Red(CR). The adsorption equilibrium was studied through isotherms
      construction at 30 degrees C, which were well described by Langmuir model. The
      adsorption capacity on the OSAC was estimated to be 303 mg/g, 217 mg/g and 167
      mg/g respectively for MB, RB and CR. This activated carbon has a similar
      adsorption properties to that of commercial ones and show the same adsorption
      performances. The adsorption kinetics of the MB molecule in aqueous solution at
      different initial concentrations by OSAC was also studied. Kinetic experiments
      were well fitted by a simple intra-particle diffusion model. The measured
      kinetics constant was influenced by the initial concentration and we found the
      following correlation: Kid = 1.55 C0(0.51).

PMID- 16465896
TI  - Ambient air temperature effects on the temperature of sewage sludge composting
      process.
AB  - Using data obtained with a full-scale sewage sludge composting facility, this
      paper studied the effects of ambient air temperature on the composting
      temperature with varying volume ratios of sewage sludge and recycled compost to
      bulking agent. Two volume ratios were examined experimentally, 1: 0: 1 and 3: 1:
      2. The results show that composting temperature was influenced by ambient air
      temperature and the influence was more significant when composting was in the
      temperature rising process: composting temperature changed 2.4-6.5 degrees C when
      ambient air temperature changed 13 degrees C. On the other hand, the influence
      was not significant when composting was in the high-temperature and/or
      temperature falling process: composting temperature changed 0.75-1.3 degrees C
      when ambient air temperature changed 8-15 degrees C. Hysteresis effect was
      observed in composting temperature's responses to ambient air temperature. When
      the ventilation capability of pile was excellent (at a volume ratio of 1:0:1),
      the hysteresis time was short and ranging 1.1-1.2 h. On the contrary, when the
      proportion of added bulking agent was low, therefore less porosity in the
      substrate (at a volume ratio of 3:1:2), the hysteresis time was long and ranging
      1.9-3.1 h.

PMID- 16465897
TI  - Investigation of air pollution concentration in Kathmandu valley during winter
      season.
AB  - The monthly concentrations of NO2, NOx, SO2 and O3 measured by a passive sampler
      from February 2003 to January 2004 showed that the air pollution during the
      winter season in Kathmandu valley was higher than the summer season. The O3 level
      was found the highest during April, May and June due to strong radiation. The
      hourly concentrations of NO2, NOx, O3 and suspended particulate matter (SPM) were
      also measured by automatic instruments on December 2003. Temperature at the
      height of 60 m and 400 m at Raniban Mountain in the northwest of Kathmandu valley
      was measured on February 2001 in the winter season and the average potential
      temperature gradient was estimated from observed temperature. Wind speed was also
      measured at the department of hydrology, airport section, from 18 February to 6
      March 2001. It was found that the stable layer and the calm condition in the
      atmosphere strongly affected the appearance of the maximum concentrations of NO2
      and SPM in the morning, and that the unstable layer and the windy condition in
      the atmosphere was considerably relevant to the decrease of air pollution
      concentrations at daytime. The emission amounts of NOx, HCs and total suspended
      particle(TSP) from transport sector in 2003 were estimated from the increasing
      rate of vehicles on the basis of the emission amounts in 1993 to be 3751 t/a,
      30570 t/a and 1317 t/a, respectively. The diurnal concentrations in 2003
      calculated by the two-layers box model reproduced the characteristics of air
      pollution in Kathmandu valley such as the maximum value of O3 and its time, the
      maximum value of NO in the morning, and the decrease of NO and NO2 at daytime.
      The comparison with the concentrations in 1993 calculated suggested that the main
      cause of air pollution was the emission from transport sector.

PMID- 16465898
TI  - Removal of natural organic matter in a typical south-China source water during
      enhanced coagulation with IPF-PACl.
AB  - Systematic investigation on enhancing removal of natural organic matter (NOM)
      using inorganic polymer flocculant (IPF), polyaluminum chloride (PACl) and
      polyacrylamide (PAM) was performed in a typical south-China source water.
      Enhanced coagulation and applying polymer flocculant-aid were compared through
      jar tests and pilot tests. Raw water and settled water were characterized and
      fractionated by resin adsorption. The results show that DOC composes major part
      of TOC. The DOC distribution keeps relatively stable all around the year with
      typical high amounts of the hydrophilic matter around 50%. The distribution
      between HoB, HoA and HoN varies and undergoes fluctuation with the year round.
      During the summer season, the HoN becomes gradually the major part in hydrophobic
      parts. PACI with the species being tailor-made shows little pH effect during
      coagulation. The enhanced coagulation dosage for PACI could be 4.5 mg/L for the
      typical source water. The highest TOC removal achieved 31%. To be economically, 3
      mg/L dose is the optimum dosage. Although hydrophilic fractions of NOM of both
      treatment strategies are removed about 30%, NOM causing UV254. absorbance were
      well removed(about 90%). Hydrophobic bases and acids fractions are much more
      removed under enhanced conditions. The hydrophilic fraction could be better
      removed using PAM, the polymer coagulant aid.

PMID- 16465899
TI  - Dye removal from wastewater using the adsorbent developed from sewage sludge.
AB  - Sewage sludge was used to develop an effective carbon adsorbent. This adsorbent
      was employed for the removal of azo dye such as Direct Dark Brown M and Acid
      Mordant Brown RH. The adsorption of dyes on this adsorbent was studied as a
      function of contact time, concentration, pH and temperature by batch method. The
      equilibrium adsorption capacity of a carbonaceous adsorbent prepared from city
      wastewater treatment plant was 502, and 329.7 mg/g of Direct Dark Brown M and
      Acid Mordant Brown RH, respectively. The experimental data were analyzed by the
      Langmuir and Freundlich models of adsorption. Equilibrium data fitted well with
      the Langmuir model. The rates of adsorption were found to conform to the
      Lagergren second-order kinetics with good correlation. The equilibrium adsorption
      capacity of the carbonaceous adsorbents was determined with the Langmuir equation
      as well as the Lagergren second-order rate equation. The most ideal pH for
      adsorption of two dyes onto adsorbents was found to be 3 and below. The results
      indicate that the carbonaceous adsorbents could be employed as a low cost
      adsorbent in the removal of dyes from wastewater.

PMID- 16465900
TI  - Anaerobic ammonium oxidation for advanced municipal wastewater treatment: is it
      feasible?
AB  - Anaerobic ammonium oxidation (ANAMMOX) is a recently developed process to treat
      ammonia-rich wastewater. There were numerous articles about the new technology
      with focus on the ammonium-rich wastewater treatment, but few on advanced
      municipal wastewater treatment. The paper studied the anaerobic ammonium
      oxidation (ANAMMOX) process with a down flow anoxic biofilter for nitrogen
      removal from secondary clarifier effluent of municipal wastewater with low COD/N
      ratio. The results showed that ANAMMOX process is applicable to advanced
      wastewater treatment with normal temperature as well as ammonia-rich high
      temperature wastewater treatment. The results indicated that ammonia removal rate
      was improved by raising the nitrite concentration, and the reaction rate reached
      a climax at 118.4 mgN/L of the nitrite nitrogen concentration. If the
      concentration exceeds 118.4 mgN/L, the ANAMMOX process was significantly
      inhibited although the ANAMMOX bacteria still showed a relatively high
      reactivity. The data also indicated that the ratio of NO(2-)-N: NH4(+)-N = 1.3:1
      in the influent was appropriate for excellent nitrogen removal. The pH increased
      gradually along the ANAMMOX biofilter reactor. When the ANAMMOX reaction was
      ended, the pH was tend to calm. The data suggested that the pH could be used as
      an indicator to describe the course of ANAMMOX reaction.

PMID- 16465901
TI  - Equilibrium and kinetics of copper(II) biosorption by Myriophyllum spicatum L.
AB  - The potential use of Myriophyllum spicatum L. biomass as a biosorbent for the
      removal of copper(II) from aqueous solution was investigated in laboratory
      condition. The sorption experiments were undertaken to obtain copper(II)
      biosorption properties of M. spicatum L., i.e. equilibrium time, the maximum
      capacity, and rate constants. Copper(II) biosorption was fast and equilibrium was
      attained within 35 min at initial copper(II) concentration of 6 mg/L. Different
      isotherm models including the Langmuir, Freundlich, Temkin and Redlich-Peterson
      model, were used to investigate the sorption capacity and isotherm. These models
      showed an excellent match with the experimental data except for the Freundlich
      model. According to the Langmuir coefficients, the maximum sorption capacity of
      copper onto M. spicatum L. was 10.80 mg/g. The kinetics of copper(II) sorption
      was also analysed and rate constants were derived. It was found that the overall
      sorption process was best described by the pseudo second-order equation, and that
      intraparticle diffusion was not the rate determining step. The results of this
      study showed that M. spicatum L. can be considered as useful vehicles for the
      removal and recovery of copper(II) from aqueous solutions.

PMID- 16465902
TI  - Nitrogen removal from sludge dewatering effluent through anaerobic ammonia
      oxidation process.
AB  - Anaerobic ammonia oxidation(Anammox) process is a novel and promising wastewater
      nitrogen removal process. The feasibility of transition of Anammox from
      denitrification and the performance of lab-scale Anammox biofilm reactor were
      investigated with sludge dewatering effluent. The results showed that Anammox
      process could be successfully started up after cultivation of denitrification
      biofilm and using it as inoculum. The transition of Anammox from denitrification
      was accomplished within 85 d. Anammox process was found suitable to remove
      ammonia from sludge dewatering effluent. The effluent ammonia concentration was
      detected to be 23.11 mgN/L at HRT of 28 h when influent ammonia concentration was
      fed 245 mgN/L, which was less than that for the national discharge standard II
      (25 mgN/L) of China. Volumetric total nitrogen loading rate was up to 584.99 mg
      TN/(L x d) at HRT of 17 h, while influent concentrations were kept 243.25 mg
      NH4(+) -N/L and 288.31 mg NO2(-) -N/L.

PMID- 16465903
TI  - Effects of simulated acid rain on fertility of litchi.
AB  - The regulatory role of calcium in fertility of pollen and pistil under simulated
      acid rain was investigated. The germination percentage of pollen treated with
      acid rain of pH 4.5 was 9.42% lower than that of control, and that of pH 3.5, pH
      2.5 and pH 1.5 were 22.47%, 45.49% and 71.62%, respectively. Simultaneously, the
      injury character of pollen was obviously observed when flowers were treated with
      acid rain of pH 3.5. The difference in fruit setting rate between the female
      flower treated with acid rain of pH 4.0 and the control was significant at p <
      0.05. Ca(NO3)2 of 0.2-0.4 mmol/L could promote pollen germination under the
      stress of acid rain. The beneficial function was reduced when calcium
      concentration surpassed 0.8 mmol/L. Spraying 2 mmol/L Ca(NO3)2 reduced the injury
      of acid rain to pistil and increased fruit-setting rate significantly. The
      physiological importance of calcium during pollen germination and pistil
      development was also discussed.

PMID- 16465904
TI  - Responses of antioxidant enzyme and photosynthesis in rape seedling to the
      combined stresses of acid rain and ultraviolet-B radiation.
AB  - Effects of the simulated acid rain (AR) and ultraviolet-B (UV-B, 280-320 nm)
      radiation with a single or two ways simultaneously (AR + UV-B) on the antioxidant
      enzyme and photosynthesis of the rape seedlings were investigated by the
      hydroponic culture. The results of static experiment indicated that the tolerance
      of rape seedling to single stress (AR or UV-B) is stronger than that to dual
      stresses (AR + UV-B). Furthermore, the dual stresses had additive effect on
      catalase activity, and a synergistic effect on MDA content, net photosynthesis
      rate, water use efficiency as well as intercellular CO2 concentration. Meanwhile,
      it has an independent effect on chlorophyll content, stomatal conductance, and
      transpiration rate as well as membrane permeability. During 64 h restoration
      course, the dynamic change in the curves of physiological and biochemical indices
      were not identical, and none of them show a simple linear variation. According to
      the static and dynamic experiments, it was found that a responsive sequence of
      catalase activity, membrane permeability, MDA content and photosynthetic
      characteristics to the above-mentioned stresses was as follows: AR + UV-B > UV-B
      > AR.

PMID- 16465905
TI  - Application of Holdridge life-zone model based on the terrain factor in Xinjiang
      Automous Region.
AB  - This study improved the application of the Holdridge life-zone model to simulate
      the distribution of desert vegetation in China which gives statistics to support
      eco-recovery and ecosystem reconstruction in desert area. This study classified
      the desert vegetation into four types: (1) LAD: little arbor desert; (2) SD:
      shrub desert; (3) HLHSD: half-shrub, little half-shrub desert; (4) LHSCD: little
      half-shrub cushion desert. Based on the classification of Xinjiang desert
      vegetation, the classical Holdridge life-zone model was used to simulate Xinjiang
      desert vegetation's distribution and compare the Kappa coefficient result of the
      model with table of accuracy represented by Kappa values. The Kappa value of the
      model was only 0.19, it means the simulation result was poor. To improve the life
      zone model application to Xinjiang desert vegetation type, a set of plot
      standards for terrain factors was developed by using the plot standard as the re
      classification criterion to climate sub-regime. Then the desert vegetation in
      Xinjiang was simulated. The average Kappa value of the second simulation to the
      respective climate regime was 0.45. The Kappa value of final modeling result was
      0.64, which is the better value. The modification of the model made it in more
      application region. In the end, the model's ecological relevance to the Xinjiang
      desert vegetation types was studied.

PMID- 16465906
TI  - Biological activity of a red-tide alga--A. tamarense under co-cultured condition
      with bacteria.
AB  - The relationship between Alexandrium tamarense (Lebour) Balech, one of red-tide
      alga, and two strains of marine bacteria, Bacillius megaterium (S7) and B.
      halmapulus (S10) isolated from Xiamen Western Sea, was investigated by evaluating
      the growth state of A. tamarense and the variation of beta-glucosidase activity
      in co-culture system. The results showed the growth and multiplication of the
      alga were related with the concentration, genus speciality of the bacteria, and
      growth stage of the alga itself. The growth of A. tamarense was obviously
      inhibited by S7 and S10 at high concentration. Either inhibition or promotion
      contributed much more clearly in earlier than in later stage of the growth of the
      alga. Furthermore, there was a roughly similar variation trend of the activity of
      extra-cellular enzyme, beta-glucosidase, in the water of the separately co
      cultured bacteria S7 and S10 with the alga. The beta-glucosidase activity (beta
      GlcA) rapidly increased during the later algal growth accompanying the increase
      of the lysis of the alga cells. The obvious inhibition of A. tamarense by marine
      bacteria at high concentration and evident increase of beta-GlcA in co-colture
      system would help us in better understanding the relationship between red-tide
      alga and bacteria, and also enlightenedus the possible use of bacteria in the bio
      control of red-tide.

PMID- 16465907
TI  - [Prematurity and methods of its screening].
AB  - OBJECTIVE: Premature delivery is an essential problem in the modern obstetrics.
      Revealing and marking the high-risk group of pregnant women in time could be used
      as one of the methods of its prevention. DESIGN: Retrospective epidemiological
      study of the aggregated data of pregnant patients. SETTING: OBGYN Clinic of the
      1st and 3rd Faculty of Medicine, Prague, FNB, FNKV. METHOD: A routine database of
      pregnant patients was generated. In our study was included the group of 2368
      patients who underwent the screening and fulfilled the condition of completion
      the data in the period from the 15th to the 20th week of pregnancy, during and
      after the birth. Database is a component of a lager database generated in the
      last 15 years. The group of premature delivery patients was marked as those who
      delivered before the beginning of the 10th month of pregnancy. MS-AFP (maternal
      serum AFP) screening values of pregnants were measured and transformed to the
      multiples of medians (MOM), corresponding to the particular week of pregnancy for
      enabling the comparison during the whole period of screening. Statistical
      investigation was performed using data analysis advanced methods. RESULTS: A
      significant statistical correlation between higher values of MS-AFP, during the
      period from the 15th to the 20th week of pregnancy, and premature deliveries were
      found. The cut-off value of 1.8 MOM MS-AFP was included to determine the higher
      risk group of patients. Women with equal or higher values of AFP were 3.8 times
      more likely to have premature delivery than those with lower AFP values (95% CI:
      2.2;6.3). Sensitivity of 25% and specificity of 92% were proven. CONCLUSION:
      According to our opinion, MS-AFP could not only be used for the hereditary
      diseases screening, but as well for performing the premature delivery screening
      at the beginning of the 2nd trimester. Cut-off value of 1.8 MOM for marking the
      higher risk group was used for marking the high-risk group. Thus the extension of
      the classical screening technique of hereditary diseases could yield also in
      other areas of the obstetrical care.

PMID- 16465908
TI  - [Diagnosis and management of infection and its role in preterm labor].
AB  - OBJECTIVE: Analysis of contemporary knowledge of infection and its role in
      etiology and pathogenesis of preterm labor. DESIGN: Review article. SETTING:
      Department of Gynecology and Obstetrics, 1st Faculty of Medicine, Charles
      University, Prague. METHODS: An overview of published data. CONCLUSION: Infection
      is considered the most significant cause of preterm labor. The current research
      tend towards searching for local cervicovaginal markers of infection. An
      important role in the prenatal care is played by cervical ultrasonography which
      together with cervicovaginal markers can sort out the group of women with high
      risk of the preterm labor. Cervicovaginal markers can reveal microbial invasion
      into higher parts of the birth canals during the intrapartal care and justify the
      administration of antibiotics especially to women with the premature rupture of
      membranes. The routine administration of antibiotics was reevaluated in the
      management of preterm labor. The question of optimal antibiotics remains open.

PMID- 16465909
TI  - [Deliveries out of medical facilities].
AB  - AIM OF STUDY: Analysis of reasons and risks of planned and unplanned deliveries
      out of medical facilities. TYPE OF STUDY: Review of literature and casuistry.
      NAME AND SITE OF DEPARTMENT: Department of Obstetrics and Gynaecology, Teaching
      Hospital Na Bulovce, 1st Faculty of Medicine, Charles University in Prague.
      MATERIAL AND METHOD: Authors of this paper are discussing published evidences
      concerning the reasons and the risks of planned and unplanned deliveries out of
      the medical facilities. They are pointing out at the activities of some
      independently practising midwives, who systematically encourage females against
      medically conducted deliveries during their prenatal courses, thus obtaining
      clients for home deliveries. At the end of the paper the authors present three
      casuistries from their own practice to document the outcomes of disinformation
      and prenatal courses guided in a wrong way. CONCLUSION: According to the results
      of foreign studies and own experience home deliveries are accompanied by
      senseless risks for mother and child. Dubitable benefits of the home surroundings
      cannot counterbalance these risks. Prenatally purposely misinformed woman and her
      partner often threaten themselves and their arriving child during labour with
      senseless risks.

PMID- 16465910
TI  - [Enucleation of intramural uterine fibroids in women at fertile age: midterm
      results of prospective clinical trials].
AB  - OBJECTIVE: To analyze clinical and reproductive outcomes of patients after
      laparoscopic (LM) or open (OM) myomectomy. DESIGN: Prospective clinical trial.
      SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine and
      General Faculty Hospital, Charles University, Prague. METHODS: Women under the
      age of 40 with intramural fibroid larger than 4 cm were indicated for myomectomy.
      LM was performed when laparoscopy revealed solitary or 2 fibroids smaller than 8
      cm; otherwise the OM was carried out. The patients were followed at 6 months
      intervals. RESULTS: 80 myomectomies with extirpation of 121 myomas was performed
      from January 2002 to April 2005. The average age was 33.5 years, average size of
      dominant fibroid 56 mm. 38% of women suffered from infertility; the mean follow
      up was 15.6 months. We performed LM in 56 cases (70%). From 24 open procedures 18
      were elective and 6 converted from laparoscopy. In 18 patients some of the
      fibroid--ischemization procedures (uterine arteries embolization or laparoscopic
      dissection, or laparoscopic myolysis) preceded myomectomy. In the group with LM
      there was significantly lower peri-procedural blood loss, lower count of
      leucocytes and CRP concentration the 2nd day after surgery, shorter stay in the
      hospital, shorter interval between surgery and conception, and lower incidence of
      early complications than in women with OM. Fibroid related symptoms fully
      disappeared in 76% of patients. 20 women from 38 that have already tried to
      conceive have achieved 22 gestations so far: 9 deliveries (2 preterm; 3 vaginal,
      6 Cesarean), 6 miscarriages, 1 ectopic and 6 ongoing pregnancies at the moment.
      CONCLUSION: In the hands of surgeons experienced in operative laparoscopy the
      enucleation of intramural uterine fibroids is safe, symptomatically effective,
      mostly low invasive procedure with good reproductive prognosis.

PMID- 16465911
TI  - [Importance of diagnostics and therapy of female subvesical obstruction in
      clinical practice].
AB  - INTRODUCTION AND OBJECTIVE: Female subvesical obstruction is frequently
      underestimated and its clinical importance is relativized. At the present time it
      is not defined precisely and most authors use the urodynamic method for
      diagnosis. The aim of the work was to evaluate the results of examination of
      subvesical obstruction by several diagnostic methods and to compare it with the
      results of therapy in symptomatic female patients with subvesical obstruction
      determined by calibration of urethra. MATERIAL AND METHODS: In the group of 31
      patients with symptoms of lower urinary tract (urgent symptomatology, obstruction
      symptomatology, relapsing infection of lower urinary pathways), where the
      calibration determined the urethra lumen less than 22Ch, the analysis of voiding
      urethrocystography. The same examinations were also made three months after
      endoscopic operation therapy (urethrotomy, endoresection of the bladder neck) and
      the comparison is described. One year after the surgery the subjective
      satisfaction of the patients was evaluated and semi-objective parameters obtained
      by analysis of the micturion diaries as well. RESULTS: Only three (9.68%) of
      patients of the cohort fulfilled all urodynamic criteria of obstruction according
      to Blaivas, only in four (12.9%) patients the pathological finding during voiding
      urethrocystography. In spite of that the deobstruction therapy reached a complete
      disappearance of the symptomatology in nine (29.0%) and a substantial improvement
      of the condition in 15 (28.4%) patients. CONCLUSION: In our opinion the clinical
      importance of subvesical obstruction in women is greater than generally
      presented. None of the urodynamic or imaging methods is able to reveal the
      obstruction safely and the calibration of urethra should be therefore a routine
      part of examination in women with symptoms of disorders in lower urinary tract.
      Uretrotomy is a simple and effective method in the therapy of subvesical
      obstruction in women with very good outcomes.

PMID- 16465912
TI  - [Using free mesh to prevent recurrence of cystocele].
AB  - OBJECTIVE: Assessment of the effect of utilisation of mesh in order to prevent
      recurrence of cystocele. SUBJECTIVE: Case study. SETTING: Department of
      Obstetrics and Gynaecology, Bata Hospital, Zlin. METHODS AND RESULTS: We evaluate
      the experience of using free mesh in the solution of cystocele. We implanted a
      total of 30 meshes. A free mesh is a preventive measure which only secondarily
      creates a suspension in the region of the anterior compartment of the vagina.
      Objective evaluation of the method requires a longer time interval.

PMID- 16465913
TI  - [Posterior free tape for the reduction of enterocele].
AB  - OBJECTIVE: Evaluation of the effect of posterior free tape for the reduction of
      enterocele and rectocele. SUBJECTIVE: Case Study. SETTING: Department of
      Obstetrics and Gynaecology, Bata Hospital, Zlin. METHODS AND RESULTS: A very
      effective solution for the reduction of large enterocele and rectocele is the
      utilization of posterior free tape. At our workstation we use posterior TVTo,
      thus the "inside out" method when, after preparation of the ischiorectal space,
      the tape is stitched into the apex of the enterocele, and by tension balances,
      the posterior compartment. From November 2003 to January 2005 we carried out 20
      operations. The anatomic effect in all on women operated was very good. In two
      cases we encountered haemorrhage with haematoma at the apex of the enterocele
      with the resulting protrusion of the tape. We resolved both cases by elimination
      of the slit tape.

PMID- 16465914
TI  - [TVT (transvaginal mesh) surgical method for complex resolution of pelvic floor
      defects].
AB  - OBJECTIVE: Assessment of the effects of a new surgical method for complex
      resolution of pelvic floor defects. SUBJECTIVE: Case study. SETTING: Department
      of Obstetrics and Gynaecology, Bata Hospital, Zlin. METHODS AND RESULTS: We
      evaluated the procedures and results of the new TVM (transvaginal mesh) surgical
      method which we used in a group of 12 patients. Ten patients had vaginal prolapse
      following vaginal hysterectomy and in two cases there was uterine prolapse and
      vaginal prolapse. Only in one case there was a small protrusion in the range of
      0.5 cm which we resolved by removal of the penetrated section. The resulting
      anatomic effect was very good in all the cases.

PMID- 16465915
TI  - [Ovulatory mucus and its pH, arborization and spermagglutination antibodies in
      women with fertility disorders].
AB  - OBJECTIVE: We studied pH of ovulatory mucus, sperm penetration through capillary
      filled with ovulatory mucus in one hour and presence of local spermagglutinating
      antibodies. METHODS: We measured pH, arborization and Kremer test in ovulatory
      mucus in 127 women with fertility disorder. Indirect mixed antiimunoglobulin
      reaction test (i-MAR-test for IgG, IgA, IgM and IgE) was used for detection of
      spermagglutinating antibodies. RESULTS: pH 7.4-9.6 (physiological limit) was
      found in 94/127 women (74%), pH < 7.4 in 33 women (26%). 60% of 94 patients with
      physiological pH had Kremer's test above 2cm/hour (normal sperm penetration in
      ovulatory mucus), in 40% of them reduction of sperm penetration (< 2cm/hour,
      swelling, shaking, cytotoxicity) was seen. Sperm antibodies in ovulatory mucus in
      24% patients with pH < 7.4 and 22% patients with physiological pH were studied.
      In 111 patients with regular menstrual cycle a classical arborization was found
      in 81%, in 14% was not proved. In 16 patients with irregular menstrual cycle
      classical arborization was observed in 11 of them. Local sperm antibodies were
      detected only in 13% of the total count of patients, it means in 17 patients.
      Their ovulatory mucus showed classical arborization. 30 healthy fertile women
      created the control group, only one secretion had pathological findings in all
      studied parameters owing to latent mycotic infection. SUMMARY: Pathological pH of
      ovulatory mucus, hormonal dysbalance, and presence of local spermagglutinating
      antibodies evidently influence penetration of sperm cells through cervix uteri.
      Otherwise pathological microbial vaginal environment can start a cross reaction
      with the surface microbes and sperm epitopes. One sign of ovulation, arborization
      of cervical ovulatory mucus, is not connected directly with the presence of local
      sperm antibodies, but insufficient estrogen influence is a sign of the reduced
      immunosuppression in cervix area.

PMID- 16465916
TI  - Breast carcinoma with three coexistant type of metaplasia: sarcomatoid, giant
      cell and squamous differantiation.
AB  - We report on a women with metaplastic carcinoma of the right breast. After
      diagnosis she had a simple mastectomy operation. Pathological investigations were
      carried out on mastectomy material. Immunohistochemical analyses were performed.
      Bizarre, malignant giant cells and diffuse inflammatory reactions were
      predominantly noted. Sarcomatous metaplasia and rare squamous metaplasia were
      also seen. There was not any area of classic intraductal, invasive ductal,
      lobular or papillary carcinoma. The patient is still alive and well for more than
      five years. This uncommon case is described and discussed, and the related
      literature is reviewed.

PMID- 16465917
TI  - [Breast cancer cell populations and its changes relation to therapy].
AB  - This review summarizes the data from published studies that dealt with
      observation of various bioparameters changes in cancer population dependant on
      used therapy. Critically evaluating these studies and looking for relations among
      separate results we are trying to estimate prognostic value of these parameters
      (likelihood of recurrence, overall survival, ...) and also their value for
      prediction of tumor response to cytostatic, hormonal or other treatment. The aim
      is selection of such tumor population characteristics the testing of them would
      enable better patient stratification in postoperative adjuvant systemic therapy.

PMID- 16465918
TI  - [Intraductal papillary proliferation of brest. Actual review and
      clinicopathological corelation].
AB  - OBJECTIVE: Complex summary addressing current view of the intraductal papillary
      lesions of breast, especially focused on morphology, exact terminology and
      clinicopathological aspects of effective therapy. DESIGN: Review article.
      SETTING: Biopsy Lab s.r.o. and Sikl's Department of Pathology, Charles University
      and Faculty Hospital, Pilsen. METHODS: Summarized recent data, diagnostic
      principals and clinicopathological recommendations of papillary breast lesions
      created comprehensive guide for daily diagnostic and therapeutic practice.
      RESULTS: The group of papillary tumors of the breast includes various lesions
      with different biologic potential. They are all presenting as pure intraductal
      lesions, but in case of multiple peripheral distribution imply possible risk for
      aggressive behavior. The reason is frequent occurrence of atypical ductal
      hyperplasia/intraductal (in situ) carcinoma in the adjacent tissue. Spectrum of
      secondary changes further complicates the diagnosis of papillary tumors,
      especially in core needle biopsy. Atypical papilloma is still very controversial
      issue and it essentially means situation when atypical ductal
      hyperplasia/conventional ductal in situ carcinoma arises in preexisting
      papillomas or extends to it from neighborhood. Generally, papillary lesions are
      suitable for effective conservative treatment in the case of proper clear
      resection margin. Finding of benign papilloma in core biopsy remains unsolved
      question yet.

PMID- 16465920
TI  - [The position of drospirenone in premenstrual syndrome teratment].
AB  - OBJECTIVE: To evaluate influence of hormonal contraceptive drospirenone on
      premenstrual syndrome (PMS). DESIGN: Overall summary of literature. AUTHOR
      AFFILIATION: ADC Sanatorium, Praha. METHODS: Review of scientific studies and
      publications. CONCLUSIONS: The author submitted current opinions on premenstrual
      syndrome, its classification, and treatment. The role of renin--aldosterone
      system in the genesis of PMS was described. Basic pharmacological characteristics
      of the remedy containing in one pill 30 mg of Ethinyl Estradiol (EE) and 3 mg of
      drospirenone are presented. Its therapeutic effects on somatic and psychological
      PMS symptoms are discussed.

PMID- 16465919
TI  - [Continuous use--the important trend of combined hormonal contraception].
AB  - OBJECTIVE: Review of literature concerning continuous regimen of combined
      hormonal contraception. DESIGN: Review article. SETTING: Department of Obstetrics
      and gynecology, Charles University, Prague. METHODS: Review and critical
      assessment of published data. CONCLUSIONS: Attitude of gynecologists and women
      toward continuous use of combined hormonal contraception was liberalized within
      the last 15 years. Continuous regimen is well tolerated; number of spotting and
      bleeding days is increased in the first two cycles, with a substantial decrease
      afterwards. Total number of bleeding days is significantly lower in comparison to
      cyclic regimen. Continual use is not accompanied by any known health risk for
      users. Moreover, there are a few medical indications for such regimen.

PMID- 16465922
TI  - [Present knowledge on inhibins B and A].

PMID- 16465921
TI  - [Informed consent in gynecology and obstetrics].
AB  - OBJECTIVE: A systematic review of recent available literature on the topic of
      informed consent, evaluation of the terminus a quo and the creation of
      theoretical basis for execution of the process of informed consent in clinical
      practice with attention to specific aspects in gynecology and obstetrics. TYPE OF
      STUDY: Review of literature. SETTING: Mother and Child Care Institute Prague,
      Chair of Gynecology and Obstetrics, IPVZ, Prague. METHODS: Review of publications
      on the given topic and implementation of general principles of medical ethics in
      the area of gynecology and obstetrics. RESULTS: The branch of gynecology and
      obstetrics brings about various controversial clinical situations, which arise
      from specific features of the branch. The informed consent is an integral part of
      the diagnostic-therapeutic process and precondition of the correct (lege artis)
      procedure. The adequate agreement with the therapy should be informed, free and
      competent. It prevents ethical crisis in conditions of an ethical conflict. The
      paper defines the content and structure of the informed consent and draws
      attention to its technical prerequisites so as to fulfill the truthfulness and
      legal validity. CONCLUSION: The informed consent is an important part of
      communication between the physician and the patient. The physician provides a
      complex, qualified, truthful and complete information. A competent patient
      accepts this kind of information and decides, based on full understanding, when
      and in what form, undergoes the recommended procedure or refuses it.

PMID- 16465923
TI  - Communicable Diseases Network Australia: National Arbovirus and Malaria Advisory
      Committee annual report 2004-05.
AB  - This report describes the epidemiology of mosquito-borne disease in Australia for
      the mosquito-borne disease season 1 July 2004 to 30 June 2005. Ross River virus
      (RRV) infections (45%), Barmah Forest virus (BFV) infections (30%) and malaria
      (19%) were the most common mosquito-borne diseases reported in 2004-05. The
      Northern Territory had the highest rate of RRV notifications and the peak
      notification rate (in February 2005) was 54 per cent less than the previous
      season. The Northern Territory also reported the highest BFV notification rate
      this season, peaking in April 2005, which was the second highest reported BFV
      notification rate since 1998. National RRV and BFV notification rates were
      highest in the 45-49 year age group. There were 799 notifications of malaria in
      2004-05 of which none were reported as locally acquired. This was the third
      highest reporting season for malaria notifications since 1998. In contrast to
      previous years in which Plasmodium vivax was the predominant species, Plasmodium
      falciparum was reported as the infecting species in 57 per cent of the malaria
      notifications and Plasmodium vivax for 34 per cent of cases. Children in the 5-9
      year age group had the highest number of cases compared to previous years in
      which the peak number of cases tended to be in young adult age groups. There were
      four cases of Kunjin virus (KUNV) and two cases of Murray Valley encephalitis
      virus (MVEV) reported in 2004-05. Sentinel chicken surveillance data for
      flaviviruses and sentinel pig surveillance data for Japanese encephalitis virus
      are reported. There were 188 notifications of dengue virus infection (DENV) in
      2004-05, of which 46 per cent (n=86) were reported as having been acquired
      overseas. Dengue serotype 4 was the most frequently reported type, accounting for
      32 per cent of cases (n=60).

PMID- 16465924
TI  - Guidelines for the use and interpretation of nucleic acid detection tests for
      Neisseria gonorrhoeae in Australia: a position paper on behalf of the Public
      Health Laboratory Network.
AB  - The Public Health Laboratory Network (PHLN) convened a workshop of Australian
      experts in Melbourne on 23 March 2005 to identify laboratory issues of relevance
      and suggest guidelines for use of nucleic acid detection tests (NADT) for
      diagnosis of gonorrhoea in Australia. The proceedings of that meeting were
      endorsed by the members of the PHLN and the Communicable Diseases Network of
      Australia. Given the present state of knowledge and experience of conditions
      currently existing in Australia, the following recommendations were made:
      Recommendation 1: Assays using detection of the cppB gene should not be used for
      either screening or supplemental assays. Recommendation 2: All in-house screening
      assays that are positive should also be positive on a reliable supplemental assay
      before a positive result is reported. Recommendation 3: All commercial screening
      assays that are positive should also be positive on a reliable supplemental assay
      before a positive result is reported. Recommendation 4: If a sample is positive
      in a screening assay but a suitable supplemental assay is negative, then the
      result should be reported as negative. Recommendation 5: Laboratories should
      ensure that the test combination they use would yield a positive predictive value
      of at least 90 per cent in a population with a prevalence of 1 per cent.
      Recommendation 6: For the purposes of test evaluation, as distinct from
      diagnostic testing, true positives be defined by meeting one or more of the
      following criteria: 1) culture positive using contemporary isolation and
      identification techniques; 2) positive result on NADTs directed to targets on
      three separate genes that are known to have discriminatory capacity; 3)
      sequencing of a gene known to separate gonococcal from non-gonococcal species.
      Recommendation 7: Inhibitor controls should be routinely included in all NADT.
      Recommendation 8: Cultures are the preferred test for samples from non-genital
      sites. If however it is necessary to perform a NADT, then more stringent criteria
      should be applied, and positive samples should meet the 'test evaluation'
      criteria for a 'true positive'. Recommendation 9: In order to properly assess the
      routine diagnostic system in Australia, the following quality assurance samples
      should be distributed in addition to the routine samples currently used: 1. cppB
      negative N. gonorrhoeae; 2. Non-gonococcal species known to cause false positive
      reactions: these should be dispatched both as a single species, as well as
      mixture with N. gonorrhoeae. In the latter circumstance, the non-gonococcal
      species should be present in 10-fold excess; 3. Urine samples: preferably a
      single patient sample, otherwise a spiked sample. 4. Validation panels should be
      made that include samples that are culture positive but PCR negative. True
      positive samples should also be made available. In addition, a process should be
      established for full phenotypic and genotypic characterisation of unidentified
      species that yield false positive results in NADT for gonococci. Recommendation
      10: Strategies should be put in place to ensure that sufficient numbers of
      gonococcal isolates are obtained to allow reliable monitoring of antimicrobial
      resistance. Recommendation 11: Public health practitioners need to define the
      relevant populations that need to be targeted and identify any that require
      enhanced surveillance.

PMID- 16465925
TI  - Surveillance of Shiga toxigenic Escherichia coli in Australia.
AB  - All Australian States and Territories have low rates (< or = 0.32 cases per
      100,000 population) of notification for Shiga toxin-producing Escherichia coli
      (STEC), except for South Australia where the rates are ten-fold higher at 2.58
      cases per 100,000 population. To explore possible reasons for the variation in
      rates we surveyed public health reference laboratories to determine the methods
      used and number of specimens tested for these organisms. Only five of eight
      jurisdictions routinely conducted testing for STEC, and polymerase chain based
      tests were most common. Culture was also common and in one jurisdiction that
      tests specimens with culture, approximately 1.2 per cent of specimens were
      positive. The notification rates for different jurisdictions reflected the number
      of specimens tested, with jurisdiction testing < or = 500 specimens having rates
      < or = 0.32 cases per 100,000 population. The use of culture as a test method may
      also influence notification rates. Public health agencies must consider the
      number of specimens tested in interpreting surveillance data.

PMID- 16465927
TI  - Salmonella typhimurium phage type 170 in a tertiary paediatric hospital with
      person-to-person transmission implicated.
AB  - Nosocomially-acquired salmonellosis is uncommonly reported in Australia. We
      report a cluster of gastroenteritis caused by Salmonella Typhimurium phage type
      170 (STm 170) centred on a tertiary paediatric hospital in Sydney, New South
      Wales from 8 to 19 May 2004. A total of 12 children had STm 170 isolated from
      faecal specimens. Of the 12 cases, seven were acquired in hospital and five in
      the community. The mean age of the cases was 4.1 years (range: 2 months to 11.2
      years). We conducted a case series investigation to generate hypotheses regarding
      the cause of this outbreak. Standardised interviews with cases' parents were
      conducted to identify potential exposures including in recently consumed food. An
      environmental investigation mapped the food preparation and storage areas,
      movements of staff caring for cases, relative case-bed locations, and duration of
      stay in these locations. Five of the seven hospital-acquired cases were
      immunocompromised with a history of prolonged and/or multiple hospital
      admissions. We found that STm 170 was probably brought into the hospital by a
      community-acquired case and spread to other in-patients through person-to-person
      transmission by hospital staff and/or patients. This study emphasises the
      importance of stringent compliance with hospital infection control practices at
      all times.

PMID- 16465926
TI  - Epidemic viral gastroenteritis in Queensland coincides with the emergence of a
      new norovirus variant.
AB  - Norovirus infections cause widespread morbidity and have significant economic
      impact on the community. An increase in outbreaks of norovirus gastroenteritis in
      hospitals, nursing homes and in the community was observed in Queensland in 2004.
      Molecular analysis of positive samples indicated the emergence of a single strain
      of norovirus. A 252 nucleotide sequence from the polymerase region (POL) was
      compared to sequences of the new variant genotype GII.4 that has caused epidemics
      in the Northern Hemisphere in 2002 and 2003. Sequence analysis indicated greater
      than 95 per cent similarity in the POL between the Queensland strain and the
      Northern Hemisphere 2002/3 GII.4 variant. Phylogenetic analysis revealed that the
      Queensland strain forms a branch within the GII.4 genotype separate from the 2002
      variant from Europe and North America. Although norovirus genotype GII.4 had
      circulated in Queensland in the past, the 2004 strain was characterised
      specifically by three nucleotides not present in any other sequences held in our
      database covering the years 2002-June 2004.

PMID- 16465928
TI  - Investigation of a multi-state outbreak of Salmonella hvittingfoss using a web
      based case reporting form.

PMID- 16465929
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, July to September 2005.

PMID- 16465930
TI  - Epidemiological features and control of an outbreak of scarlet fever in a Perth
      primary school.
AB  - Scarlet fever was associated with feared outbreaks and mortality in the 19th
      Century. It occurs sporadically in modern society and infection is readily
      treated with antibiotics. We report on a scarlet fever outbreak in children
      attending a primary school in Perth, Western Australia, in late 2003. A total of
      13 cases were identified over a five week period. Six of the cases were pre
      primary children (ages 4 to 5) from the same class of 26 children (attack rate
      23.1%). Three of the remaining seven cases were older siblings of pre-primary
      cases who developed scarlet fever after their younger siblings. Screening of the
      children and teachers from the two pre-primary classes at the school yielded 12
      positive pharyngeal swabs for group A Streptococcus. Emm-typing of the screening
      isolates indicated that a common strain was circulating within the outbreak pre
      primary class, with four of six isolates identified as emm-type 3. The overall
      group A Streptococcus carriage rate in screened students in this class was 31.6
      per cent and the carriage rate for emm-type 3 was 21.1 per cent. Carriers were
      treated with oral penicillin V to eradicate carriage and control the outbreak. No
      further cases of scarlet fever were reported after the treatment of pharyngeal
      carriers. Outbreaks of scarlet fever still occur in young children and
      identification and treatment of carriers may still be valuable.

PMID- 16465931
TI  - The epidemiology of kuru in the period 1987 to 1995.
AB  - Kuru is an encephalopathy or neuro-degenerative disease found only in the Okapa
      District of the Eastern Highlands Province of Papua New Guinea. It is always
      fatal, with a subacute course, on average, of about 12 months from onset to
      death. In the 9-year period 1987 to 1995 there were 66 deaths from kuru, 17 males
      and 49 females. The number of deaths per year ranged from 3 to 12. All deaths
      occurred south of a line drawn through the centre of the kuru region
      perpendicular to the axis of social change. The mean age at death was 49 years,
      with a gradual increase in this age with time. The last patient aged in their 20s
      died in 1987 and the last in their 30s died in 1991. The period shows a waning
      epidemic, with dramatically fewer deaths than in the early years of
      epidemiological surveillance 30 years before. Nevertheless, the clinical features
      and duration of the disease were unchanged. Transmission of kuru stopped by 1960
      and patients seen in the period 1987-1995 showed long incubation periods, which
      in 1995 would have been at least 35 years. The proportion of males was much
      higher than in the early years; because males were effectively exposed only in
      childhood their incubation periods were in many cases likely to be over 50 years.
      The work of the Kuru Surveillance Team in maintaining a rigorous surveillance of
      kuru epidemiology over this period is described.

PMID- 16465933
TI  - Communicable and vaccine-preventable conditions under surveillance by the APSU:
      2004 update.

PMID- 16465932
TI  - Q fever vaccine uptake in South Australian meat processors prior to the
      introduction of the National Q Fever Management Program.
AB  - Despite the availability of a vaccine, the incidence of Q fever disease among
      populations at risk continues to be high. Q fever is an important cause of
      morbidity for workers, particularly in the meat and agricultural industries.
      Following an increase in 1998 in the number of Q fever notifications among meat
      processors to the Communicable Disease Control Branch, South Australia, a survey
      was conducted in the same year to assess the uptake of Q fever immunisation
      programs in meat processors and to identify barriers to offering these programs.
      This survey was conducted prior to the introduction of the National Q Fever
      Management Program in 2001 that provided a targeted vaccination program to
      specific at-risk occupations. The results of the survey highlighted that very few
      meat processors in South Australia offered a Q fever immunisation program to
      their workers. More importantly, this article highlights that there was a wide
      variety of attitudes and beliefs about Q fever disease and its prevention. These
      attitudes and beliefs have the potential to impact on whether workers at risk are
      offered or seek Q fever vaccination. Previous attitudes may return and levels of
      protection in at-risk occupations will decrease without a concerted effort at a
      state level. A replication of this study should benchmark the prevailing
      attitudes about Q fever programs. In response to the 1998 survey a number of
      strategies and initiatives were developed to address the barriers to Q fever
      vaccination in South Australian meat processors. The National Q Fever Management
      Program (2001-2005) further enhanced the ability to address barriers such as
      vaccine cost.

PMID- 16465934
TI  - A report from the Communicable Diseases Network Australia, 1 July to 30 September
      2005.

PMID- 16465937
TI  - [Internal medicine according to the new Swiss executives].

PMID- 16465935
TI  - Supplementary report: surveillance of adverse events following immunisation among
      children aged less than 7 years in Australia, 1 January to 30 June 2005.

PMID- 16465936
TI  - Communicable diseases surveillance: highlights for 3rd quarter, 2005.

PMID- 16465938
TI  - [Addictions].
AB  - This year reviews on the addictions emphasizes five aspects, on a bio-psycho
      social perspective: (1) The relationship between methadone and cardiotoxicity.
      (2) The introduction of Eye Movement Desensibilization and Reprocessing (EMDR).
      (3) The apparition of a possible specific pharmacotherapy for excessive gambling.
      (4) A better knowledge of the relationship between cannabis and psychoses. (5)
      Resistance to treatment in the doctor-patient relationship.

PMID- 16465939
TI  - [Endocrinology].
AB  - There is now convincing evidence that the risks of hormone replacement therapy in
      post-menopausal women exceed its benefits. Similarly, it has now been shown that
      the current use of low-dose oral contraceptives significantly increases the risk
      for cardiac and arterial thrombotic events. With regard to hypothyroidism, it is
      now clearly established that the adjunction of T3 to T4 does not offer any
      benefits. Furthermore, a study has now demonstrated that patients with no
      symptoms of coronary heart disease can be started safely on the full replacement
      dose of T4 rather than titrating the dose over a prolong period of time. Finally,
      several theses are now well documented where chinese herbal products contain
      thyroid hormones or glucocorticoids potentially leading to serious side effects
      and our patients should be informed about these dangers.

PMID- 16465940
TI  - [Geriatrics].
AB  - This overview covers several topics related to the management of frequent
      problems in elderly persons. Several studies have shown that treatment of
      neuropsychiatric symptoms of dementia with psychotropic medication is modestly
      effective and could increase the risk of adverse events, including death.
      Influenza vaccination in long term care residents was shown to be effective in a
      systematic review, while post-exposure prophylaxis with oseltamivir, a
      neuraminidase inhibitor, seems cost-effective in vaccinated residents during an
      epidemics in a nursing home. Conflicting results were observed in studies of
      fracture prevention with vitamine D. Finally, one study showed the potential
      pifalls of guidelines developed for specific chronic medical conditions when
      applied simultaneously to older patients with complex comorbidities.

PMID- 16465941
TI  - [Haemostasis. Aspirin and clopidogrel platelet resistances].
AB  - Articles on antiplatelet "resistance" or "nonresponder" subjects now appear in
      the medical literature or in the media on a regular basis. The clinical
      consequences of such biological resistances are yet uncertain. In this review, we
      describe the concepts of specific and non specific resistances according to the
      tests used and summarize the main studies up to now. If antiplatelet drug
      resistances are shown to be predictive of cardiovascular events in large
      prospective studies, tailoring antiplatelet drugs could be beneficial and,
      therefore, warranted. New compounds with a more potent effect are emerging and
      might be useful in clinically relevant resistances.

PMID- 16465942
TI  - [Infectious disease].
AB  - Several articles published in 2005 offer new knowledge in infectious diseases
      treated by practitioners. This paper discusses viral (influenza) and bacterial
      (pneumococci and legionella) respiratory infections. Resistant staphylococci,
      different from healthcare-associated MRSA, are now found in community. The
      article assesses that epidemics of Norovirus infections are common during winter
      time. The screening for treatment of asymptomatic bacteriuria is not recommended.
      The possible development of a successful vaccine to prevent herpes zoster is
      finally reminded.

PMID- 16465943
TI  - [Therapeutical advances in neurology in 2005].
AB  - We report on the therapeutic advances in Neurology that took place over the last
      year. The purpose here is not to provide a detailed and exhaustive listing of
      each study of 2005, but rather to emphasize those that might be the most
      significant for the clinician. Following this idea, we have chosen to mention not
      only the therapeutical advances, but also, sometimes, the disappointments of
      2005.

PMID- 16465944
TI  - [New obesity and metabolic syndrome treatment: rimonabant].
AB  - CBI endocannabinoid system receptors localized in the hypothalamus and the
      nucleus accumbens are known to regulate hunger. Hyperstimulation of the CBI
      receptors lead to an increase of food intake, but also to an increase of
      lipogenesis, decrease of adiponectin and increase of insulin resistance.
      Rimonabant is the first CBI central and peripheral blocker, tested in
      international trials (RIO-lipids, RIO-Europe and RIO-North America). Significant
      results on weight reduction, increased adiponectin and improved metabolic
      syndrome have been demonstrated. Rimonabant is a new pharmacological therapy and
      very interesting for tackling obesity and metabolic syndrome.

PMID- 16465945
TI  - [Osteoporosis treatment].
AB  - As for any chronic disease, adherence to osteoporosis treatment is low. Folates
      and vitamin B12 decrease hip fracture risk in elderly Japanese with stroke.
      Raloxifene (Evista) decreases the incidence of positive estrogen receptor breast
      cancer and could prevent cardiovascular events in patients at high risk.
      Strontium ranelate (Protelos) prevents hip fracture in elderly women. The action
      of alendronate (Fosamax) on bone mineral density and markers of bone remodelling
      is of higher amplitude than that of risedronate (Actonel). Once monthly
      ibandronate (Bonviva) increases bone mineral density in post menopausal women
      with osteoporosis. Excessive suppression of bone remodelling and osteonecrosis of
      the yaws could be related to bisphosphonate intake.

PMID- 16465946
TI  - [Pneumonology. Ultrasound-guided transbronchial needle aspiration].
AB  - After discovering a lung cancer without extrathoracic metastases, the
      preoperative mediastinal check-up is of great importance to determine the
      patients operability. The 78% specificity of activity measuring FDG in a PET
      examination is clearly insufficient to avoid a biopsy of the incriminated lymph
      nodes. The investigation of a suspected malignant adenopathy justifies a complete
      examination by mediastinoscopy or-tomy, which are considered gold standards. The
      transbronchial fine needle aspiration guided by ultrasound (EBUS-TBNA)
      constitutes the recent evolution of TBNA, method known for 20 years now but
      underused. Depending on the operators skill, this new procedure needs a learning
      curve before being able to replace mediastinoscopy.

PMID- 16465947
TI  - [How should inhaled corticosteroids be prescribed in asthma?].
AB  - The treatment of persistent asthma is based on the concept of a maintenance
      therapy (inhaled corticosteroids +/- long-acting beta-2-agonists) that is
      associated with a reliever therapy (short-acting beta-2-agonists). A recent study
      has suggested a new approach: budesonide/formoterol combination as both
      maintenance and reliever medication. The patient is told to adjust his medication
      by himself according to his symptoms. The advantage and potential weakness of
      this approach will be discussed in the present review.

PMID- 16465948
TI  - [Psychiatry].
AB  - During the year 2005 much of the attention was given to the debate on the risk of
      suicide during treatments with selective serotonin reuptake inhibitors. Our
      review concludes with a moderate increased risk of suicidal behaviour but not a
      risk of death by suicide. Caution, not panic, is indicated, particularly for
      children and adolescents given that, in this age group, benefits of these drugs
      have not been well established. We also report two synthesis concerning the
      latest developments in the fields of cognitive psychotherapy for depressive
      disorders (rather stimulating news) and of pharmacotherapy for borderline
      personality disorders (no breaking news).

PMID- 16465949
TI  - [Vaccinology update 2005: a new category of recommendations for optimal vaccine
      protection].
AB  - A new category of vaccination recommendation was introduced to increase the
      equity of the access to the information that relatively rare but severe diseases
      may be prevented by immunization. This decision was supported by the observation
      of a 2-level vaccination practice in Switzerland, reflected by the fact that
      children from paediatrician parents are better immunized than other children. The
      introduction of "additional recommended vaccinations" to the baseline
      immunizations should correct this inequity. In 2006, parents may choose to
      protect their children against meningitis and invasive diseases caused by
      pneumococcus or group C meningococcus. The challenge is now to inform parents
      about this new possibility of an optimal prevention, in addition to baseline
      immunizations.

PMID- 16465951
TI  - [A misleading panacea?].

PMID- 16465950
TI  - [2005, the year of the bird flu].

PMID- 16465952
TI  - [About the difficult relationship between France and alcoholic beverages].

PMID- 16465953
TI  - [Story of the first partial face transplant].

PMID- 16465954
TI  - [Viral hepatitis A develops into disease requiring mandatory reporting in
      France].

PMID- 16465955
TI  - [2006, the virtual party].

PMID- 16465956
TI  - Three Tennessee nursing students make a difference in South Africa.

PMID- 16465957
TI  - From the TNA president.

PMID- 16465958
TI  - Center for American Nurses.

PMID- 16465960
TI  - [Evaluating the model SCORE for calculating cardiovascular risk in primary health
      care].

PMID- 16465959
TI  - Patient safety and culture: nurses play a key role.

PMID- 16465961
TI  - [Cancer cluster analysis. The case of the Campdora District in Girona, Spain].
AB  - A conglomerate of cases may be defined as the onset of a number of cases of a
      disease larger than would be expected for a certain population group,
      geographical area or a certain timeframe. In the case of cancer, the study of
      conglomerates entails a number of specific characteristics as compared to other
      groups of diseases. This work is aimed at proposing a protocol affording the
      possibility of conducting the study of cancer conglomerates in time and/or space.
      This article is illustrated with a practical application in the case of the
      Campdora District in Girona. Following a proposed protocol for the study of
      conglomerates, a description is provided of several statistical tools making it
      possible to draw a comparison among the existence of time-related groupings, as
      well as the related risk. During the period studied (1994-2002), no excessive
      statistically significant number of cancer cases seemed to have occurred in the
      Campdora District in Girona.

PMID- 16465962
TI  - [Comparison of the SCORE and REGICOR models for calculating cardiovascular risk
      in cardiovascular disease-free individuals at a healthcare center in Barcelona,
      Spain].
AB  - BACKGROUND: No studies have been published to date comparing SCORE, REGICOR and
      Framingham models. This study is aimed at analyzing how the REGICOR and SCORE
      functions classify cardiovascular risk, their correlation and concordance with
      Framingham (1998) and whether any differences exist among them with regard to the
      cardiovascular risk factors in high-risk groups. METHODS: Descriptive cross
      sectional study conducted in primary care. A total of 851 individuals within the
      35-74 age range, free of cardiovascular diseases and selected by simple random
      sampling were included. A study was made of the percentage of high-risk patients
      with Framingham (> or = 20% ten-year risk), SCORE (> or = 5% ten-year risk) and
      REGICOR with cutoff points > or = 20%, > or = 15%, > or = 10% and > or = 5% at 10
      years, given that with REGICOR > or = 20% there are hardly any high-risk cases. A
      comparison was drawn between the correlation (Pearson's r) and concordance (Kappa
      index) of the REGICOR and SCORE high-risk individuals as compared to Framingham.
      RESULTS: The high-risk percentages respectively found were: 23.3% with
      Framingham; 15.2%; with SCORE; and 1.4%, 5.8%, 17.6% and 57.0% with REGICOR with
      the cutoff points described. REGICOR has a 0.99 correlation, SCORE a 0.78
      correlation. REGICOR > or = 10% showed a better concordance (Kappa 0.83) than
      SCORE (Kappa 0.61). On comparing the cardiovascular risk factors of the high-risk
      cases (> or = 20% Framingham, > or = 5% SCORE and > or = 10% REGICOR), SCORE
      showed higher prevalence of diabetes and a lower prevalence of
      hypercholesterolemia (p<0.05). CONCLUSIONS: REGICOR showed a good correlation
      with Framingham. With the > or = 10% cutoff point, it classifies a number of
      individuals as high-risk similar to SCORE and fewer than Framingham. The SCORE
      model would treat a number of patients similar to the REGICOR > or =10% model
      with hypolipemiant drugs, however showing lesser evidence of effectiveness of the
      treatment.

PMID- 16465964
TI  - [Cohort study methodology of the ITINERE Project on heroin users in three Spanish
      cities and main characteristics of the participants].
AB  - BACKGROUND: Cohort studies make it possible to monitor the health impact of drug
      use and to identify related factors. We describe the methodology and baseline
      characteristics of a cohort of heroin users designed with this objective.
      METHODS: The participants were 991 young, community-recruited heroin users in
      Barcelona, Madrid and Seville. Most subjects were named by other participants
      (39.7%) or by non-participating drug users or ex-users (44.7%). A computer-aided
      questionnaire was administered (self-administered with audio for questions
      related with sex). A dried-blood spot sample was collected and anthropometric
      measurements were made. Both participants and recruiters received remuneration.
      Univariate and bivariate statistical methods were used. RESULTS: Some 42.4% had
      changed the main route of heroin administration, mainly to injection in Barcelona
      and to the pulmonary route in Seville. About 75.8% (Barcelona), 49.8% (Madrid),
      and 15.5% (Seville) had injected drugs in the last 12 months. In Madrid and
      Seville, 96-97% used heroin in base form, while in Barcelona heroin hydrochloride
      predominated. Heroin and cocaine were frequently mixed in the same dose
      (generally base cocaine in Madrid and Seville, and cocaine hydrochloride in
      Barcelona). CONCLUSIONS: Important geographic differences persist in the
      prevalence of drug injection and in the patterns of heroin and cocaine use, which
      could explain the unequal distribution of some health problems. The difficulties
      encountered in recruiting the sample suggest that the incidence of heroin use has
      declined considerably.

PMID- 16465963
TI  - [Comparison of the SCORE and Framingham models in calculating high cardiovascular
      risk for a sample of males within the 45-65 age range in Asturias, Spain].
AB  - BACKGROUND: The Spanish Interdisciplinary Committee for Cardiovascular Prevention
      has recently drafted a consensus for adapting the European Cardiovascular
      Prevention Guide to the Spanish population, using SCORE as the risk-calculation
      method. This study is aimed as ascertaining the differences involved in changing
      over from the Framingham to the SCORE criterion in the classification of males
      within the high-risk group. METHODS: Descriptive cross-sectional study conducted
      in primary care. A total of 379 males within the 45-65 age range, corresponding
      to four (4) groups from general practitioners from three healthcare centers in
      the Principality of Asturias. MAIN MEASUREMENTS: calculation of the
      cardiovascular risk and high-risk prevalence by the conventional Framingham
      method and according to SCORE. High-risk prevalence curve estimated by logic
      regression. RESULTS: The high-risk prevalence according to the Framingham
      equation was 24% (CI95%=19.9-28.7) and was 17.9% (CI95%=14.3-22.3) for SCORE, the
      difference being statistically significant (p=0.02). The SCORE model shows lower
      prevalences among subjects under age 60 and higher for those over age 60. Among
      male smokers, SCORE shows lower prevalences among individuals under 58 years of
      age, the high-risk males with Framingham and low-risk with SCORE being younger,
      smokers and having lower average blood pressure figures and moderate cholesterol
      figures. CONCLUSIONS: On applying the SCORE model, we classify fewer males as
      high-risk, especially among those under 58 years of age who are smokers having
      moderate cholesterol figures than when the Framingham scale is used.

PMID- 16465966
TI  - Selection criteria for attachments.

PMID- 16465965
TI  - [Voluntary interruption of pregnancy among women in an health district within the
      1998-2002 period. Almeria, Spain].
AB  - BACKGROUND: The immigrant population has undergone an increase in Andalusia as a
      whole and in Almeria in particular. The primary healthcare districts manage the
      requests for voluntary interruption of pregnancy. This study is aimed as
      describing the trend in requests for voluntary interruption of pregnancy among
      immigrant and non-immigrant women in the "Levante-Alto Almanzora" Health District
      of Almeria. METHODS: Descriptive study conducts during the 1998-2002 period.
      STUDY MATERIAL: requests for voluntary interruption of pregnancy, Andalusian
      Institute of Statistics demographic data, temporary medical care cards. VARIABLES
      STUDIED: Age, date of request, pregnancy > or =, or < 12 weeks, type of
      population (immigrant or non-immigrant). Voluntary interruption of pregnancy
      rates were calculated per 1000 women within the 15-49 age range and the relative
      risk with confidence intervals and statistical significance for studying the
      relationship between the number of interruptions and populations type. RESULTS: A
      total of 224 requests were studied. The largest number were made in 2002, for a
      3.1 rate. The age group making the largest number of requests was the 20-24 age
      range (29.5%). Ninety-five percent (95%) of the women were less than 12-weeks
      pregnant. A total of 52.7% were immigrant women, a greater risk of requesting
      voluntary interruption of pregnancy having been found among immigrants as
      compared to native Spanish women, RR of 66.45 (CI 95%: 36.11-122.28) in 2001;
      292.8 (CI 95%: 91.12-940.9) in 1999. CONCLUSIONS: Voluntary interruption of
      pregnancy was found to have increased in the public services, particularly among
      immigrant women, within the period studied.

PMID- 16465968
TI  - Extensive ceramic rehabilitation using CAD/CAM restorations.

PMID- 16465967
TI  - A historical perspective of synthetic ceramic and traditional feldspathic
      porcelain.
AB  - Ceramics were invented by the Chinese during the T'ang Dynasty, where they
      quickly became a precious commodity. By the early 18th Century, ceramics found
      its way into dentistry due to its high strength, biocompatibility, and
      malleability. Today, ceramic materials are a staple in dentistry, available in
      both naturally based and partially synthetic formulas. Most recently they have
      become available as quartz-glass synthetic materials manufactured under
      controlled conditions to eliminate the inconsistencies and impurities inherent in
      the naturally based counterpart. LEARNING OBJECTIVES: This article details the
      discovery of porcelain and its role as a precious substance throughout the world
      and time, from its initial use as ornamental earthenware to its practical
      application in modern dentistry. Upon reading this article, the reader should:
      Understand the historical significance of porcelain. Recognize the fundamental
      constituents and physical properties of both natural feldspathic porcelains and
      fully synthetic ceramics used in dentistry.

PMID- 16465969
TI  - Digital imaging applications for the dental office.

PMID- 16465970
TI  - Dentin hypersensitivity: Part I.

PMID- 16465971
TI  - Enhancing facial appearance with aesthetic dentistry, centric relation, and
      proper occlusal management.
AB  - Dramatic alterations that affect a person's appearance can be accomplished by
      changing the shade, shape, and location of individual teeth in the dental arch.
      With further application of scientifically documented anatomic principles,
      dentists can change a person's facial appearance without using unnatural tooth
      shapes and/or creating nonphysiologic changes in the masticatory system. What is
      most important is that the clinician does not have to open a patient's vertical
      dimension of occlusion (VDO) to exact a change in facial aesthetics. A
      conservative approach that is harmonious with the natural human form can be
      successfully accomplished. LEARNING OBJECTIVES: This article presents a
      conservative methodology towards enhancing a patient's facial appearance in order
      to fulfill their aesthetic objectives. Upon reading this article, the reader
      should: Realize how a basic understanding of both the anatomy of the
      temporomandibular joint (TMJ) and how it interacts with the dentition can help
      provide a beneficial and stable occlusion for aesthetic dentistry. Understand how
      the VDO is established and how to decide when and if an increase of VDO is
      necessary for treatment.

PMID- 16465972
TI  - Clinical and laboratory procedures for aesthetic metal-ceramic anterior
      restorations.

PMID- 16465973
TI  - Lingualized occlusion: an occlusal solution for edentulous patients.
AB  - Occlusion is a critical component in any aspect of prosthodontic care including
      that related to the treatment of dentate, partially dentate, or edentulous
      patients. When complete dentures are fabricated for an edentulous patient,
      occlusion has a considerable influence on the outcome of treatment. Due to the
      relative simplicity involved in development of a lingualized occlusal scheme by
      dental laboratory technicians, this approach has gained favor among practitioners
      who are able to evaluate and/or correct tooth arrangements for complete dentures.
      This article will highlight the influences of a lingualized tooth arrangement in
      complete denture occlusion as it relates to improving edentulous patients'
      function and quality of life; it will also demonstrate a predictable approach to
      achieving lingualized occlusion in complete denture prosthodontics.

PMID- 16465974
TI  - Application of hypochlorite to etched and dried dentin surface for optimum
      adhesion.

PMID- 16465975
TI  - Margin placement: the importance of visual acuity.

PMID- 16465976
TI  - Conservative restoration of characterized anterior dentition using composite
      resin.

PMID- 16465977
TI  - Achieving aesthetic success with an immediate-function implant and customized
      abutment and coping.
AB  - The absence of teeth in the anterior region often results in a number of negative
      consequences compromising appearance and facial anatomy, as well as patients'
      self-esteem and social behavior. Dental implants have increasingly become a
      viable option for achieving natural-looking restorations. The success of anterior
      restorations, however, depends upon several factors. The following case
      presentation discusses these factors as well as the implementation of clinical
      and laboratory procedures for the restoration of a missing anterior tooth.
      LEARNING OBJECTIVES: This article demonstrates an implant surgical procedure and
      restorative sequence used to replace a fractured single anterior tooth. Upon
      reading this article, the reader should: Understand how dental implants can be a
      viable solution based upon factors within the proximity of the region being
      restored. Realize that optimal aesthetics can be achieved when the final abutment
      is installed at the time of implant placement.

PMID- 16465978
TI  - Increased food intake after the addition of amylase-rich flour to supplementary
      food for malnourished children in rural communities of Bangladesh.
AB  - BACKGROUND: In Bangladesh, as in other developing countries, protein-energy
      malnutrition is mostprevalent among children during weaning. After weaning,
      children are often fed cereal-based diluted low-calorie porridge, resulting in
      growth-faltering. OBJECTIVE: To assess the effect on food intake of adding
      amylase-rich flour (ARF) from germinated wheat to supplementary food among
      children in nine rural Community Nutrition Centers under the Bangladesh
      Integrated Nutrition Project (BINP). METHODS: A total of 166 malnourished
      children of either sex, aged 6 to 24 months, received one of three diets randomly
      allocated to the Community Nutrition Centers. The composition of the diets was
      the same; however, the consistency and calorie density were altered by adding
      either ARF or water. Thirty-five children received the standard supplementary
      food of the BINP (S-SF), 65 received supplementaryfood with added ARF (ARF-SF),
      and 66 received supplementary food with added water (W-SF). The children were
      studied for six weeks. Results. The mean +/- SD intake of supplementaryfood from
      a single meal by children completing six weeks on the diets was higher for
      children receiving ARF-SF (33.91 +/- 8.25 g) than for those receiving S-SF (25.66
      +/- 6.73 g) or W-SF (30.26 +/- 8.39g) (p < .05 for both comparisons). The weight
      of vomited food was significantly higher for children receiving W-SF than for
      children in the other two groups. Weight gain and increments in length and weight
      for-height were higher for children who received ARF-SF than for children in the
      other two groups, but the differences were not statistically significant. The
      acceptability ofARF-SF was higher than that of the two other diets. The
      additional cost of adding 2 g of ARF to the diet was about Taka 0.25 (U.S. dollar
      1 = Taka 48). CONCLUSIONS: Addition of ARF to existing standard supplementary
      food, as used under the BINP program, is a simple and effective means to increase
      the intake of food by changing its consistency, thus making it easier for
      malnourished children to ingest.

PMID- 16465979
TI  - Effects of a food supplementation program on the nutritional status of pregnant
      women in Bangladesh.
AB  - BACKGROUND: The Government of Bangladesh implemented a comprehensive nutrition
      intervention in 1997 to reduce the rates of malnutrition among women and
      children. The pilot program, the Bangladesh Integrated Nutrition Program (BINP),
      adopted a multisectoral approach targeting women and children through food
      supplementation, home gardening, and health and nutrition education. OBJECTIVE:
      This paper estimates the effectiveness of BINP's food supplementation and
      nutrition education on the nutritional status of pregnant women. Methods. Three
      effectiveness measures were considered: target efficiency, improvements in the
      nutritional status of beneficiaries, and the persistence of nutritional effects.
      To isolate the effects of the intervention, the nutritional status of
      participants and nonparticipants was compared after controlling for various
      demographic and socioeconomic characteristics. Data were collected in 2000 from a
      random sample of 3262 households in a BINP intervention area. RESULTS: Thirty
      nine percent of pregnant women were correctly targeted by the program's food
      supplementation activities. The nutrition program reduced the prevalence of
      thinness among participant pregnant women by about 3 percentage points per month
      of enrollment. The prevalence of thinness among program graduates was 62%, which
      was much higher than that of the matched (nonparticipant) group (35%). This
      finding is perplexing but it may simply imply that those who enrolled at the
      initial phase of the project were severely underweight and they fell back to
      their original status within a short period of time. CONCLUSIONS: The nutrition
      program was intended to improve the nutritional status of women in the longer run
      through the provision of nutrition education during the food supplementation
      phase. The prevalence of thinness or severe underweight in women who exited the
      program after completion of the enrollment period was found to be much higher
      than in women of similar age and socioeconomic status in the community. This
      apparent lack of persistence of program benefits requires careful re-evaluation
      of alternative mechanisms for improving the long-term nutritional status of
      women.

PMID- 16465980
TI  - Effect of iron supplementation during pregnancy on birthweight: evidence from
      Zimbabwe.
AB  - BACKGROUND: Iron deficiency in pregnant women has been shown to reduce the oxygen
      supply to the fetus, cause intrauterine growth retardation, and increase the risk
      of premature delivery and reduced birthweight. Yet the effects of iron
      supplementation programs on pregnancy outcomes are not well documented for
      developing countries. OBJECTIVE: To examine the relation between iron
      supplementation of mothers during pregnancy and children's birthweight using data
      from a national population-based survey in Zimbabwe. METHODS: The analysis uses
      information on 3559 births during the five years preceding the 1999 Zimbabwe
      Demographic and Health Survey. The effect of iron supplementation during
      pregnancy on birthweight was estimated by multiple regression, controlling for
      potential confounding effects of prenatal care, child's sex and birth order,
      mother's education and nutritional status (measured by body-mass index),
      household living standard, smoke exposure, and other variables. RESULTS: Babies
      born to mothers who received iron supplementation during pregnancy were 103 g
      heavier (95% confidence interval, 42-164; p = .001), on average, than babies born
      to mothers who did not receive iron supplementation during pregnancy. The
      difference was 64 g (95% confidence interval, 2-125; p = .043) for children whose
      birthweights were taken from health cards and 163 g (95% confidence interval, 44
      281; p = .008) for children whose birthweights were reported by their mothers.
      CONCLUSIONS: Iron supplementation during pregnancy is associated with
      significantly higher birthweight, independent of other pregnancy care factors,
      mother's nutritional status, smoke exposure, and a number of demographic and
      socioeconomic factors. Prenatal iron supplementation programs can improve
      pregnancy outcomes and promote child survival in developing countries.

PMID- 16465981
TI  - Vitamin A deficiency and child survival in sub-Saharan Africa: a reappraisal of
      challenges and opportunities.
AB  - BACKGROUND: Children with vitamin A deficiency have higher risk of morbidity and
      mortality than vitamin A-sufficient children. Estimates on the potential child
      survival benefits of vitamin A deficiency control are needed for policy and
      program advocacy. OBJECTIVE: To determine the current prevalence of children at
      risk for vitamin A deficiency in sub-Saharan Africa in order to estimate the
      potential child-survival benefits of effective and sustained policies and
      programs for the control of vitamin A deficiency in this region. METHODS:
      Estimates of the prevalence of vitamin A deficiency generated in 1998, data from
      11 nationally representative vitamin A deficiency surveys conducted in sub
      Saharan Africa between 1997 and 2003, and the measured effects of vitamin A
      deficiency on child mortality were combined to estimate the prevalence of
      children at risk for vitamin A deficiency in sub-Saharan Africa and the potential
      child-survival benefits of effective and sustained policies and programs for the
      control of vitamin A deficiency in this region. RESULTS: Our analysis shows that
      in the absence of effective and sustained policies and programs for the control
      of vitamin A deficiency, an estimated 42.4% of children 0 to 59 months of age in
      sub-Saharan Africa (43.2 million children) are at risk for vitamin A deficiency.
      Such effective and sustained policy and program action for the control of vitamin
      A deficiency can bring about a potential 25% reduction in mortality in children 0
      to 59 months with respect to 1995 mortality levels (i.e., before the onset of
      large-scale vitamin A supplementation programs in sub-Saharan Africa).
      CONCLUSIONS: Effective and sustained control of vitamin A deficiency has the
      potential to be among the most cost-effective and high-impact child-survival
      interventions in sub-Saharan Africa. A stronger political commitment and a more
      appropriate level of investment in the effective control of vitamin A deficiency
      could make a large contribution toward the attainment of the Millennium
      Development Goal for the reduction of child mortality rates by two-thirds between
      1990 and 2015. Among the many challenges that Africa will need to face in the
      coming years, vitamin A deficiency is one that can be overcome. The need is
      urgent, and the solutions are known, effective, and affordable.

PMID- 16465982
TI  - Community assessment of availability, consumption, and cultural acceptability of
      food sources of (pro)vitamin A: toward the development of a dietary intervention
      among preschool children in rural Burkina Faso.
AB  - BACKGROUND: Vitamin A deficiency remains a public health problem in Burkina Faso
      and elsewhere in the developing world. Dietary diversification is a promising
      strategy that needs to be explored to strengthen the country's ongoing
      supplementation program. OBJECTIVE: The purpose of this study was to identify
      locally available and acceptable (pro)vitamin A-rich foods to be included in a
      dietary intervention addressing vitamin A deficiency in children aged six months
      to three years. METHODS: A food ethnographic study combining recall methods,
      observation, and focused group discussion was conducted in the dry and rainy
      seasons. Thirty-five mother-child pairs were randomly selected and included in
      the study. RESULTS: The dietary pattern of children was characterized by low
      diversity with extremely low energy and vitamin A intake in both seasons. The
      study identified the availability of numerous (pro)vitamin A-rich foods, but
      these foods are either not consumed or consumed by few in low amounts and/or in
      low frequencies. The main constraining factors identified are related to
      financial accessibility (for liver), seasonal availability (for egg, milk, mango,
      papaya, and green leafy vegetables), and beliefs related to consumption and
      preparation (for green leafy vegetables). However, the study also revealed that
      the study population associated all identified (pro)vitamin A-rich foods with
      positive attributes such as health, strength, and vitamin richness, which might
      offer an entry point for designing and implementing dietary interventions.
      CONCLUSIONS: Based on the findings of this formative research, intervention
      strategies with mango and liver are proposed to improve the vitamin A intake and
      status of children in the rural areas of Burkina Faso.

PMID- 16465983
TI  - Power from below: enabling communities to ensure the provision of iodated salt in
      Kyrgyzstan.
AB  - BACKGROUND: In Kyrgyzstan, as in many countries around the world, progress in
      universal salt iodization has been slow because of difficulties in enforcing
      existing national regulations. OBJECTIVE: To study the effects of community
      testing of the iodine content of salt in households, at local retailers, and at
      wholesale markets on the percentage of households using iodized salt in Naryn
      Oblast, a region of Kyrgyzstan. METHODS: In response to a stated community
      priority to address iodine deficiency in Naryn Oblast, volunteers from village
      health committees and personnel of Primary Health Care units living in the
      communities were trained in testing salt using test kits. A phased introduction
      of two testing components was conducted in 2002-2003 in two areas with a combined
      population of 160,000. The two components included testing of salt for iodine
      content by community members in as many households as possible (Component 1) and
      testing of retail salt for iodate content by community members and by retailers
      at wholesale markets (Component 2). Results from these two components provided
      the data for this study. RESULTS: For Component 1, salt testing reached 65% of
      households; coverage of iodized salt increased from 87.6% to 96.8% within 5 to 7
      months (averages of the two areas; p < .001), mostly owing to a great decrease in
      the variation among settlements. For Component 2, in area 1, the percentage of
      households using iodated salt increased from 71.0% to 90.3% within 5 to 7 months,
      whereas the percentage of households using iodinated salt decreased from 18.6% to
      5.6%. In area 2, the percentage of households using iodated salt increased from
      65.2% to 76.2% within 5 to 7 months, with no change in the percentage of
      households using iodinated salt (21.7% and 20.8%). The differences between areas
      I and 2 are highly significant (p < .001). At 18 to 21 months, the percentage of
      households using iodated salt was 97.5% in area 1 and 90.2% in area 2. The
      intervention cost around U.S. dollars 1500. CONCLUSIONS: Testing salt in a large
      percentage of households is an effective, low-cost approach to increasing the
      percentage of households using iodized salt to satisfactory levels in a very
      short time. Empowering community members to check salt at retailers and retailers
      to check salt at wholesale markets with test kits for iodated salt can rapidly
      ensure almost exclusive consumption of iodated salt in households.

PMID- 16465984
TI  - Development of fortified dried broken rice as a complementary food.
AB  - BACKGROUND: Commercially produced dried broken rice is widely used to prepare
      complementary foods for Thai infants, and it is both convenient and acceptable to
      persons from all socioeconomic classes. However, inadequate levels of calcium,
      iron, thiamine, and folate are common in complementary foods for breastfed
      infants. OBJECTIVE: We developed dried broken rice fortified with these nutrients
      at levels recommended by the 2001 guidelines of the World Health Organization.
      METHODS: The fortification process involved predrying broken rice at 90 degrees C
      for 1 hour, soaking in a nutrient solution (2:1 ratio of rice to solution), and
      drying at 70 degrees C for 1 hour and 50 minutes. Calcium lactate or calcium
      lactate gluconate was the calcium source, and ferrous sulfate, ferrous lactate,
      or ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA) was the iron source.
      The vitamin sources were thiamine hydrochloride and folic acid. The product
      contained 40 mg of calcium, 5.3 mg of iron, 0.08 mg of thiamine, and 11 microg of
      folate per 20-g serving. RESULTS: Approximately 5% and 10% of calcium and iron,
      respectively, were lost during processing, with a thiamine loss of approximately
      13%, and a folate loss ranging from 17% to 23%. The thiamine loss during
      accelerated storage (42 degrees C for three months) was not significant (p >
      .05). CONCLUSIONS: NaFeEDTA was the most appropriate iron fortificant because it
      provided prolonged product stability and high in vitro dialyzability.

PMID- 16465985
TI  - Nutrient content of complementary foods based on processed and fermented sorghum,
      groundnut, spinach, and mango.
AB  - BACKGROUND: Many African mothers use gruels made of maize and sorghum as
      complementary foods for their infants because they cannot afford the cost of
      nutritionally superior commercial weaning foods. OBJECTIVE: To improve the
      nutritional quality of traditional sorghum gruels used as complementary foods for
      children between six months and five years in the northern part of Cameroon.
      METHODS: Sorghum grains were processed by dehulling, sprouting, dehulling and
      cooking, and sprouting and cooking, then fermented using Saccharomyces cerevisae
      and tested for nutritional quality. The processed samples were analyzed for their
      nutrient composition and the digestibility of proteins and carbohydrates.
      RESULTS: The resulting products showed a significant reduction in antinutritional
      factors (e.g., phenolic compounds and phytates). In addition, germination
      improved the in vitro digestibility of proteins and carbohydrates. These effects
      were enhanced by fermentation of the resulting sorghum flour, regardless of how
      grains were pretreated, although the protein and mineral content remained low.
      Use of a composite flour made from pretreated sorghum, groundnut, spinach, and
      mango improved the protein, mineral, and vitamin A and C content of the gruels.
      Fermentation of composite flours resulted in an improvement in the protein
      content. CONCLUSIONS: This study, conducted under local conditions and using
      local technology, describes an opportunity for improving the quality of
      complementary foods using local ingredients.

PMID- 16465986
TI  - Food and nutrition concerns in Aceh after the tsunami.

PMID- 16465987
TI  - Food, nutrients, and child growth: the role of specific foods and nutrients in
      child malnutrition and implications for food assistance programs.

PMID- 16465988
TI  - Improving rice nutrition: challenges and practical approaches for iron
      fortification.

PMID- 16465989
TI  - Biotechnology, biofortification, and global health.
AB  - Deficiencies of micronutrients such as iron, zinc, and vitamin A afflict over
      three billion people (more than 50% of the world's population), most of them
      women, infants, and children in resource-poor families in the developing world.
      This global crisis in nutritional health is the result of dysfunctional food
      systems that do not consistently supply enough of these essential nutrients to
      meet the nutritional requirements of high-risk groups. Deficiencies of
      micronutrients result in increased morbidity and mortality rates, lost worker
      productivity, stagnated national development, permanent impairment of cognitive
      development in infants and children, and large economic costs and suffering to
      those societies affected. Because agricultural systems are the primary source of
      all micronutrients for all people, changes in agricultural policies and systems
      must be made that will ensure consistent and adequate supplies of all essential
      nutrients to all people. Additionally, the nutrition and health sectors must turn
      to agricultural interventions as a primary tool in their efforts to eliminate
      malnutrition from the world if they want to ensure sustainability.
      Biotechnological advances show great promise for improving the output of
      bioavailable micronutrients from agricultural systems that feed the poor. This
      paper reviews some of these opportunities and discusses the questions and
      concerns that should be raised when these technologies are used to improve the
      micronutrient status of vast numbers of people who are dependent on staple food
      crops for their sustenance. Further, important issues surrounding micronutrient
      bioavailability and plant food factors that affect it are discussed.

PMID- 16465990
TI  - Update on the development of virus-resistant papaya: virus-resistant transgenic
      papaya for people in rural communities of Thailand.
AB  - Papaya (Carica papaya L.) is one of the most important and preferred crops in
      rural communities in Thailand. Papaya ringspot virus (PRSV) is a serious disease
      of papaya throughout Thailand. Efforts to control the virus by various methods
      either have not been successful or have not resulted in sustainable control. In
      1995, collaborative research by the Department of Agriculture of Thailand and
      Cornell University to develop transgenic papaya resistant to PRSV was initiated.
      Two local Thai cultivars were transformed by microprojectile bombardment with the
      use of a nontranslatable coat protein gene of PRSV from Khon Kaen. Numerous
      kanamycin-resistantplants were regenerated and were inoculated with the PRSV Khon
      Kaen isolate for selection of resistant lines. Since 1997, promising RO
      transgenic lines have been transferred to the research station at Thapra for
      subsequent screenhouse tests and selection of the most PRSV-resistant lines. In
      selection set 1, three R3 lines initially derived from Khaknuan papaya showed
      excellent resistance to PRSV (97% to 100%) and had a yield of fruit 70 times
      higher than nontransgenic Khaknuan papaya. In selection set 2, one R3 line
      initially derived from Khakdam papaya showed 100% resistance. Safety assessments
      of these transgenic papayas have so far found no impact on the surrounding
      ecology. No natural crossing between transgenic and nonmodified papaya was
      observed beyond a distance of 10 m from the test plots. Analysis of the
      nutritional composition found no differences in nutrient levels in comparison
      with the nonmodified counterparts. Molecular characterization by Southern
      blotting revealed three copies of the transgene presented; however, no coat
      protein product was expressed. Data on additional topics, such as the effects
      offeeding the transgenic papaya to rats and the stability of the gene inserts,
      are currently being gathered.

PMID- 16465991
TI  - Seed-specific expression of the lysine-rich protein gene sb401 significantly
      increases both lysine and total protein content in maize seeds.
AB  - The sb401 gene from potato (Solanum berthaultii) encoding a pollen-specific
      protein with high lysine content was successfully integrated into the genome of
      maize plants, and its expression was correlated with increased levels of lysine
      and total protein content in maize seeds. A plasmid vector containing the sb401
      gene under the control of a maize seed-specific expression storage protein
      promoter (P19z) was constructed and introduced into maize calli by
      microprojectile bombardment. The integration of the sb401 gene into the maize
      genome was confirmed by Southern blot analysis, and its expression was confirmed
      by Western blot analysis. Quantification of the lysine and protein contents in R1
      maize seeds showed that, compared with the nontransgenic maize control, the
      lysine content increased by 16.1% to 54.8% and the total protein content
      increased by 11.6% to 39.0%. There were no visible morphological changes in the
      vegetative parts and seeds of the transgenic maize plants. Lysine and protein
      analysis of the transgenic maize grains showed that the levels of lysine and
      total protein remained high for six continuous generations, indicating that the
      elevated lysine and total protein levels were heritable. These results indicate
      that the sb401 gene could be successfully employed in breeding programs aimed at
      improving the nutritional value of maize.

PMID- 16465992
TI  - Sharing Malaysian experience with the development of biotechnology-derived food
      crops.
AB  - Biotechnology-derived food crops are currently being developed in Malaysia mainly
      for disease resistance and improved post harvest quality. The modern
      biotechnology approach is adopted because of its potential to overcome
      constraints faced by conventional breeding techniques. Research on the
      development of biotechnology-derived papaya, pineapple, chili, passion fruit, and
      citrus is currently under way. Biotechnology-derived papaya developed for
      resistance to papaya ringspot virus (PRSV) and improved postharvest qualities is
      at the field evaluation stage. Pineapple developed for resistance to fruit black
      heart disorder is also being evaluated for proof-of-concept. Other biotechnology
      derived food crops are at early stages of gene cloning and transformation.
      Activities and products involving biotechnology-derived crops will be fully
      regulated in the near future under the Malaysian Biosafety Law. At present they
      are governed only by guidelines formulated by the Genetic Modification Advisory
      Committee (GMAC), Malaysia. Commercialization of biotechnology-derived crops
      involves steps that require GMAC approval for all field evaluations and food
      safety assessments before the products are placed on the market. Public
      acceptance of the biotechnology product is another important factor for
      successful commercialization. Understanding of biotechnology is generally low
      among Malaysians, which may lead to low acceptance of biotechnology-derived
      products. Initiatives are being taken by local organizations to improve public
      awareness and acceptance of biotechnology. Future research on plant biotechnology
      will focus on the development of nutritionally enhanced biotechnology-derived
      food crops that can provide more benefits to consumers.

PMID- 16465993
TI  - Nutritional and safety assessments of foods and feeds nutritionally improved
      through biotechnology.

PMID- 16465994
TI  - Food biotechnology and consumer perceptions in Asia.

PMID- 16465995
TI  - Urinary iodine excretion levels among young adult women in a district with
      endemic iodine deficiency in Haryana State, India.

PMID- 16465996
TI  - Delayed construction of the bilio-digestive anastomosis in right living donor
      liver transplantation.
AB  - We describe a two-step procedure in the transplantation of a right lobe liver
      graft obtained from a living donor, in which the biliary anastomosis is delayed
      until the day after the actual implantation of the graft. The purpose of the two
      step procedure is to minimize the factors that might contribute to biliary
      complications in living donor liver transplantation (LDLT). Three patients who
      received a graft with two hepatic ducts underwent Roux-en-Y hepatico
      jejunostomies during a separate procedure the day after the implantation of the
      graft. Length of intubation, recovery of enteral alimentation, and hospital stay
      were similar to the patients who underwent one-step transplant. No biliary or
      infectious complications occurred. Delaying the hepatico-jejunostomy when two
      ducts are present and a bilio-digestive anastomosis is planned has no negative
      impact on the postoperative course of the patients but can ameliorate the
      conditions under which the anastomoses must be performed.

PMID- 16465997
TI  - Delayed detection of a traumatic diaphragmatic injury caused by positive pressure
      ventilation: a case report and a proposed system of classification of delayed
      diagnosis of traumatic injuries.
AB  - The establishment of regional trauma centers in the United States has resulted in
      a significant reduction in morbidity and mortality from traumatic injuries. It
      has also led to a decrease in the incidence of delayed diagnosis of injuries
      ("missed injuries"), which are not detected during the initial evaluation of
      these patients. The surgeon managing an acutely injured trauma patient in the
      initial "golden hour" is faced with leadership, organizational, diagnostic, and
      therapeutic challenges. The algorithmic approach to the care of the trauma
      patient has led to the development of protocols to eliminate or at least reduce
      the incidence of these undetected injuries. The majority of these missed injuries
      are difficult to reliably detect by conventional diagnostic modalities, are
      usually asymptomatic, or attention was erroneously diverted to other more overt
      injuries. We report a case of a patient who sustained a traumatic laceration of
      his left hemi-diaphragm, which was detected only after positive pressure
      mechanical ventilation was discontinued. A proposed system of classification of
      delayed diagnoses is also presented.

PMID- 16465998
TI  - Two years of wait and 7000 miles of journey: the tale of a gossypiboma.
AB  - Postoperative retention of a foreign body is an infrequent but well-recognized
      complication. A case of a retained swab in the abdominal cavity ("gossypiboma")
      has been reported. In view of the high morbidity (50%) and mortality (10%) that
      may result from potential complications, as well as underlying medico-legal
      implications, it is important to ensure that every effort is made to prevent such
      occurrences. Presentation of gossypiboma may vary and can be caused by
      pseudotumoral, occlusive, or septic syndrome. Ultrasonography that shows a "hyper
      reflective mass with hypoechoic rim along with a strong posterior shadow" and
      computed tomography that reveals "a whirl-like spongiform pattern in a hypodense
      mass with a thick peripheral rim" are considered the mainstay of investigations.
      These findings, along with a high index of suspicion, can help make a
      preoperative diagnosis.

PMID- 16465999
TI  - Serous cystadenoma of the pancreas has abnormal imaging characteristics: report
      of a case.
AB  - Thanks to the development of image diagnosis and the spread of screening by
      ultrasonography, an increasing number of cystic lesions of the pancreas are being
      recognized. Serous cystadenoma of the pancreas is relatively rare among the
      cystic tumors of the pancreas in Japan. Herein, we report a case of serous
      cystadenoma that was difficult to diagnose. The tumor was located in the head of
      the pancreas, and it was indicated hypovascularity by enhanced computed
      tomography. These images did not indicate serous cystadenoma. After operation, we
      diagnosed correctly from the immunohistochemical examination. Although serous
      cystadenoma was believed to be in benign tumors, it has recently been revealed
      that serous cystadenoma has malignant potential. Therefore, serous cystadenoma
      that is difficult to diagnose should be completely resected.

PMID- 16466000
TI  - Progression and regression of biloma after laparoscopic cholecystectomy evaluated
      by computed tomography.
AB  - The natural course of biloma after laparoscopic cholecystectomy (LC) was
      successfully followed and evaluated by computed tomography (CT). Biloma is one of
      the major complications after LC. However, the processes of biloma progression
      and regression have not yet been reported in detail. We encountered a case of
      minor leakage of bile juice after LC. Unexpected injury of the Luschka duct
      (accessory bile duct) was suspected. We examined this patient periodically by CT,
      which is very reliable and easy to use for postoperative evaluation. Biloma
      gradually developed within 6 months as we suspected. We successfully detected the
      presence of the Luschka duct by bilomagraphy. The patient was symptomatically
      silent for the next 6 months as the size of the biloma spontaneously decreased.
      Therefore, it is not always necessary to carry out treatment for biloma after LC
      if the patient has no symptoms. This is the first report that shows the
      progression and regression of biloma evaluated precisely by CT.

PMID- 16466001
TI  - Retroperitoneal para-aortic paraganglioma.
AB  - Paragangliomas or chemodectomas are neoplasms that arise from neural crest cells
      and histologically resemble their adrenal counterpart, the pheochromocytoma.
      Seventy-one percent of the extra-adrenal paragangliomas are located in the
      superior or inferior paraaortic area. This tumor usually presents as an abdominal
      mass producing back pain. Tumor localization has improved remarkably through the
      use of computed tomography and I131 metaiodobenzyl-guanidine scintigraphy,
      particularly when tumors are hormonally active. Surgical excision remains the
      mainstay of treatment, although vascularity can at times make excision difficult.

PMID- 16466002
TI  - Implementation of a clinical pathway for laparoscopic colorectal surgery.
AB  - The purpose of this study was to assess through questionnaire the validity of our
      original clinical pathway for laparoscopic colorectal surgery. From 2001 to 2002,
      laparoscopic colorectal surgery was performed in 52 patients in our institution.
      All patients were out of bed within 3 days after the operation. The average
      postoperative hospital stay was 10.9 days. The implementation rate of the
      clinical pathway was 100%. As to the results of the questionnaire, 92.4% of the
      patients felt they could be discharged within 7 days after the operation, whereas
      >95% of the patients wanted to go home on a Sunday/holiday or the day before. All
      but 2 patients (96.2%) were satisfied with our therapy. In a clinical pathway for
      laparoscopic colorectomy, a high implementation rate and patients' satisfaction
      can be achieved by taking into account the patients' viewpoints; however, better
      patient education is necessary to shorten postoperative stay.

PMID- 16466003
TI  - Myoblast transplantation on the beating heart.
AB  - Cellular cardiomyoplasty using various types of donor cells is now validated by a
      large number of experimental studies. We report a case of cellular
      cardiomyoplasty performed on a beating heart using autologous skeletal myoblasts,
      thus combining the efficacy of both procedures. Approximately 2.5 g of rectus
      femoris muscle tissue biopsy was taken from the patient and cultured using a
      patented procedure to generate human myoblasts. The cell type and the purity of
      the cell culture were ascertained by immunostaining for human desmin expression.
      Under direct vision and stabilization with the Octopus III tissue stabilizer,
      3.70 x 10(8) myoblasts in 3 ml of the patient's own serum were injected into the
      myocardium in 20 sites on the anterior wall and near the apex on the posterior
      wall, in and around the infarcted areas. In this case report, this procedure was
      found to be a safe and viable option, with improvement in cardiac function.

PMID- 16466004
TI  - Is gastropexy required for all cases of gastric volvulus in children?
AB  - Gastric volvulus (GV) is rare in the pediatric age group. The presentation is
      varied, and surgery in the form of gastropexy is recommended. We examine the
      place of gastric fixation in the management of these patients. The authors
      retrospectively reviewed five cases of gastric volvulus treated at their
      institute and noted presenting symptoms and signs, studies performed, associated
      anomalies, surgery done, and outcome. All patients had associated diaphragmatic
      abnormalities. Two patients had acute volvulus; three had a chronic presentation.
      Chest X-ray and barium meal were diagnostic. All patients underwent surgical
      correction of the diaphragmatic anomaly with detorsion of the stomach. Gastropexy
      was done in only one patient. All patients recovered without any complications
      and have been well. GV must be suspected in the appropriate clinical setting;
      chest X-rays and barium meals are the best studies in suspected cases. Gastropexy
      or gastrostomy is not necessary for a successful outcome in secondary volvulus.

PMID- 16466005
TI  - Prospective randomized study of internal oblique aponeurotic flap repair for
      tension-free reinforcement of the posterior inguinal wall: a new technique.
AB  - In recent years, Lichtenstein's tension-free hernioplasty has emerged as the gold
      standard for hernia surgery. However, it entails placement of a mesh and thus is
      costlier material-wise compared with herniorrhaphies. A new technique of internal
      oblique aponeurosis flap (IOAF) has been devised by the author that incorporates
      the advantages of Lichtenstein's technique (low recurrence, less pain) without
      its additional costs. A prospective study was carried out to compare the two
      techniques. The mean time for surgery was significantly less for the IOAF repair
      compared with the Lichtenstein's repair. Complications were fewer with the IOAF
      repair, especially local heaviness and induration. IOAF repair also had less
      material cost than Lichtenstein's repair. The technique of IOAF repair for
      inguinal hernia is fast, safe, and has less material cost compared with the
      Lichtenstein tension-free repair.

PMID- 16466006
TI  - Parotid surgery: review of 107 tumors (1990-2002).
AB  - Tumors of the parotid gland are uncommon. We performed a retrospective study to
      analyze the clinical, diagnostic, and therapeutic features of a group of
      patients. We reviewed the clinical and the surgical records of a series of 109
      patients who were recommended for surgery because of parotid tumors by the
      Plastic and Reconstructive Service of Sao Joao Hospital, Portugal, between 1990
      and 2002. The following parameters were evaluated: age, sex, gland afflicted,
      symptoms, and duration of symptoms, diagnostic procedures, treatment methods,
      follow-up, and recurrences. Pleomorphic adenoma was the most common tumor
      (63.5%). In the majority of cases, fine-needle aspiration cytology was used.
      Swelling was the most frequent clinical finding. In 68.2%, superficial
      parotidectomy was performed. There were five cases of permanent facial palsy, and
      10 patients developed Frey's syndrome. Recurrent disease was seen in six
      patients. For the majority of tumors, superficial parotidectomy is an effective
      treatment with acceptable morbidity.

PMID- 16466007
TI  - Long-term results of omental transplantation in chronic occlusive arterial
      disease (Buerger's disease).
AB  - Salvage of limbs affected by Buerger's disease has been a dilemma for surgeons.
      Palliative sympathectomy relieves vasospasm only in the early stages.
      Reconstructive procedures are usually not possible because graft patency rates
      are low. Limb amputation often is the only available management option. We used
      the omentopexy technique to salvage these limbs. Omentopexy was performed in 273
      patients with sympathectomy failure in end-stage Buerger's disease. The technique
      of omentopexy is presented. The outcome has been analyzed with respect to
      improvement of clinical symptoms, ulcer healing, and angiographic and color
      Doppler studies. Of the 273 patients, 250 available for follow-up were followed
      for a mean of 7.5 years (range, 1-19.5 years). One- to 5-years follow-up (n = 110
      cases) revealed good results in 94% of patients. Long-term follow-up (5-15 years;
      n = 140 cases) showed good results in 85% of patients.

PMID- 16466008
TI  - Laparoscopic repair of a Morgagni-Larrey hernia.
AB  - Morgagni-Larrey hernia is a congenital type of diaphragmatic hernia. It is quite
      uncommon, particularly when it occurs on the left side of the diaphragm. This is
      a report of a case of a large left-side diaphragmatic hernia through the foramen
      of Morgagni treated by laparoscopy. The hernia was repaired by incorporating and
      fixing a polypropylene double-filament mesh into the defect, leaving the sac in
      mediastinum. The patient recovered promptly after the hernia repair, and there
      was no recurrence or complaints 30 months after surgery. Our conclusion is that
      laparoscopically repairs of Morgagni hernias with a prosthetic material are a
      safe and effective treatment. A literature review also shows that laparoscopic
      techniques are the gold standard in diaphragmatic hernias repairs.

PMID- 16466009
TI  - [Tumor necrosis factor alpha (TNF-alpha) and its receptors: sTNF-alphaRI i sTNF
      alphaRII in chronic pancreatitis].
AB  - The exact immunologic mechanisms underlying chronic pancreatitis (CP) are not
      clearly identified yet. The role of TNF-alpha in CP has been evaluated only
      rarely. The possible pathogenetic role of the cytotoxic TNF-alpha signal
      transduction pathway in the clinical course of CP has been recently suggested.
      The aim of the study was to assess the plasma concentration of TNF-alpha as well
      as its receptors: sTNF-alpha RI and sTNF-alphaRII in patients with CP of
      different clinical stage. TNF-alpha, sTNF-alpha RI and sTNF-alpha RII plasma
      concentrations have been measured with enzyme-linked immunosorbent assay (ELISA)
      in 39 patients with CP as well as in age- matched healthy volunteers. The
      percentage of smokers was not different in CP and the control group. The CP stage
      has been classified according to Cambridge scoring system. The correlation
      between above mentioned parameters and clinical data, as disease duration and
      concomitant diabetes has been assessed. The mean TNF-alpha concentration in
      patients with CP was 24,6 +/- 15,07 pg/ml which was significantly higher (p<0,01)
      than in control group--11,3 +/- 2,01 pg/ml. The mean values of TNF-alpha
      receptors concentrations: sTNF-alphaRI and sTNF-alphaRII have also been
      significantly higher (p<0,01) in patients with CP, compared to controls. No
      significant differences in TNF-alpha, sTNF-alphaRI, sTNF-alphaRII values
      dependently on patient alcohol consumption, diabetes and the disease duration
      have been found. However, the significantly higher TNF-alpha and sTNF-alphaRII
      concentration (p<0,05) has been observed in patients with Cambridge IV stage
      compared to patients of all other stages. We conclude that TNF-alpha signal
      transduction pathway may play a significant role in chronic pancreatitis,
      particularly of advanced clinical stage.

PMID- 16466010
TI  - [Pharmacogenetics of the local thrombolysis in patients with deep vein
      thrombosis].
AB  - Thrombophilia, the state of increased tendency for blood clotting, is considered
      the disorder of a complex etiology, caused by both environmental and genetic
      factors. As gene variants predisposing to thrombophilia and influencing the
      increased risk of vein thrombosis might influence response to local thrombolysis,
      the aim of the work was to characterize the pharmacogenetic conditions for local
      streptokinase treatment in patients with a deep vein thrombosis (DVT) of lower
      extremities based on the following polymorphism analyses: G1691A polymorphism of
      factor V (FV), G20210A polymorphism of prothrombin (PT), A4250G (Thr312Ala)
      polymorphism of fibrinogen-alpha (FGA), G(-455)A polymorphism of fibrinogen-beta
      (FGB), 4G/5G polymorphism of plasminogen activator inhibitor type 1(PAI-1) and
      insertion/deletion (I/D) polymorphism of tissue plasminogen activator (t-PA). The
      study included 40 DVT patients who underwent a local thrombolytic treatment
      within 14-day period from diagnosis. Full recanalization was achieved in 20
      subjects (50%) [group R(+)], whereas incomplete or total lack of recanalization
      was identified in the remaining 20 patients [group R(-)]. No major complications
      of thrombolytic treatment occurred in the studied group. In the case of
      prothrombin gene all individuals carried homozygous wild type genotype (GG).
      Prevalence of the genotypes and alleles of the remaining five polymorphisms did
      not differ significantly between the groups R(+) and R(-). Neither sex nor age,
      smoking or time period from diagnosis to introduction of the thrombolytic
      treatment significantly influenced treatment efficacy. The results of the study
      suggest that a local thrombolysis with streptokinase introduced within two week
      period from the diagnosis is a safe and efficient method of treatment for deep
      vein thrombosis of lower extremities. However, size of the group is insufficient
      to clearly determine the association between investigated polymorphisms and
      efficacy of local treatment with streptokinase.

PMID- 16466011
TI  - [Inflammatory markers and adiponectin plasma level in patients with type 2
      diabetes].
AB  - INTRODUCTION: In patients with carbohydrate or lipid disturbances higher
      inflammatory markers levels and lower adiponectin levels were observed. These
      observations suggest the potential role of those markers in the pathogenesis of
      diabetes, obesity and atherosclerosis. INVESTIGATED GROUP AND METHODS: 25 type 2
      diabetic patients (group A) and 15 patients without diabetes (group B) were
      included into the study. Glycated haemoglobin (HbAlc), total cholesterol and
      triglycerides, interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha) and
      adiponectin levels were measured in blood samples. Fasting plasma glucose and
      fasting plasma insulin were measured to calculate index of insulin resistance
      (homeostasis model assessment--IR/HOMA-IR/). RESULTS: Mean adiponectin level was
      significantly lower in patients with type 2 diabetes than in control patients
      (7,4 microg/ml vs 12,3 microg/ml; p<0,05). Blood levels of fasting insulin, IL-6,
      TNFalpha and HOMA-IR index were higher in people with diabetes than in control
      subjects but the differences were not statistically significant. No significant
      correlations were observed between adiponectin and inflammatory markers level and
      total cholesterol, triglyceride, HOMA-IR level and blood pressure. CONCLUSIONS:
      The findings indicate that adiponectin level is lower in patients with type 2
      diabetes. We did not manage to confirm significantly elevated inflammatory
      markers levels in this group of patients.

PMID- 16466012
TI  - [Assessment of hemoptysis etiology among patients hospitalized in Pneumonology
      Departament of Medical University of Gdansk in the years 1998-2002].
AB  - A retrospective analysis of 3400 clinical records of patients hospitalized in
      Pneumonology Department of Medical University of Gdansk between 1998-2002 year
      was performed. 431 (12,7%) of them was admitted to hospital because of
      hemoptysis. The cause of hemoptysis was determined in 380 (82,2%) cases. The most
      common diagnosis was neoplasm--174 cases (40,4%), between them squamous cell
      carcinoma (47,7%). In 51 cases (11,8%) the etiology of hemoptysis was
      undetermined.

PMID- 16466013
TI  - [Transient psychiatric abnormalities in patients with acute myocardial
      infarction].
AB  - Psychiatric abnormalities (PA) are often observed in patients (pts) in the
      Coronary Care Units. The origin of such abnormalities is not always clear, but it
      is known that they may aggravate patients status and interfere with further
      treatment. The aim of this study was to analyze the factors potentially
      predisposing to the occurrence of PA in pts with acute myocardial infarction
      (AMI). MATERIAL: The study group consisted of 200 consecutive pts hospitalized
      due to AMI. In 63 of them (Group A) the in-hospital course was complicated by PA
      (agitation, anxiety, hallucinations). Sex- and age-matched 63 pts of the
      remaining 137 pts which had not PA were control group (Group B). METHODS: The
      data related to coronary artery disease history, AMI diagnosis and treatment were
      withdrawn from hospital reports. Second group of parameters was focused on
      history of central nervous system (CNS) diseases, vision and audition ability,
      stimulant or drug addiction. The data about patient's employment and familial
      status, level of education, self-estimation of quality of life (QoL) in hospital
      were the third group of parameters. The second and third group of data were
      questionnaire-based information. RESULTS: There were no significant differences
      between groups in arrhythmias, localization of AMI, percentage of pts with high
      level of education, neither living alone or with family, jobless, retired or
      employed ones. Also self-evaluation of QoL was distributed similarly. The
      parameters which differed Group A versus Group B were respectively: history of
      CNS diseases (48% vs 20%, p<0,05), in particular--CNS traumas (18% vs 2,3%,
      p<0,05) and ischemic episodes (10% vs 0%, p = 0,039), thrombolytic (non
      percutaneous interventional) treatment 23,8 vs 4,6%, p<0,05), handicap of visual
      ability (16% vs 0%, p--0,012), nicotinism (30% vs 9,1%, p<0,05), left ventricle
      ejection fraction <40% (34% vs 5%, p<0,05), treatment with atropine (12,7% vs 0%,
      p = 0,012) or amiodarone (16,7% vs 0%, p = 0,037). CONCLUSION: History of
      neurological diseases, thrombolytic treatment, left ventricle ejection fraction
      <40%, handicap of visual ability, nicotinism and amiodarone or atropine in
      pharmacological treatment are factors which may be helpful to predict PA in pts
      with AMI. Cumulation of such factors increases a risk of occurrence of transient
      psychiatric abnormalities. Proper psychoactive pretreatment should be applied in
      pts with such profile in purpose to avoid behavior related complications.

PMID- 16466014
TI  - [Thromboembolic and haemorrhagic complications in patients treated with
      anticoagulants after artificial heart valve replacement. Risk factors dependent
      on quality of anticoagulant treatment].
AB  - Thromboembolic (TE) and hemorrhagic (H) complications are the most significant
      causes of morbidity and mortality in patients treated with oral anticoagulants
      (OA) after implantation of artificial valvular prostheses. The risk of
      complications is dependent on recommended target INR ranges and quality of
      anticoagulation treatment. We studied 358 patients with a mean age 56.9 +/- 10.3
      (who underwent 144 mitral, 172 aortic, 42 both artificial heart valve
      replacement). The follow up was averaged 36.7 +/- 12.1 month. Linearized
      incidents of TE events was 2.7%/pty, H events--4.15%/pty. The quality of
      anticoagulant treatment based on following parameters: averaged INR +/- SD,
      percentage measurements of INR within the target range 2.5-3.5, within the broad
      range 2-4 and under 2 and over 5. Average frequency of tests, SD/averaged INR X
      100%--was similar in patients with TE and H complications and event free
      patients. Significant differences were found when a shorter period of time-3
      months preceding the TE or H incident was analized compared with the average
      results of measurements of event free patients. The patients with TE and H
      complications have statistically significant higher fluctuation ratio than event
      free patients (respectively: 1.09 -/+ 0.71 and 1.71 -/+ 1.06 vs 0.5 -/+ 0.32, p =
      0.04 and 0.02 ) CONCLUSIONS: 1. The risk of TE and H complications was dependent
      on high fluctuation of INR values in the period of 3 months before the event. 2.
      The worse control of measurements of INR in the period of 3 months before the
      event in comparison with yearly values within the recommended target ranges show,
      that TE and H complications are directly dependent on period of poor INR control.

PMID- 16466015
TI  - [Musculoskeletal manifestations as the first symptom of acute lymphoblastic
      leukemia. A case report].

PMID- 16466017
TI  - [Bronchial smooth muscle cells in airway remodeling in asthma and COPD].

PMID- 16466016
TI  - [HIV-associated nephropathy. Case report].
AB  - The clinical case described below forces us to ask two basic questions: whether
      the patient is suffering from two separate, co-existing illnesses, i.e. primary
      nephritic syndrome or the nephritic syndrome in connection with Schoenlein-Henoch
      disease, with accompanies the HIV infection, or nephropathy, development of which
      has been triggered by HIV infection.

PMID- 16466018
TI  - [The role of inflammatory factors in risk assessment of renal insufficiency in
      diabetes mellitus].

PMID- 16466019
TI  - [Rare forms of ACTH-independent Cushing's syndrome--new diagnostic challenges].

PMID- 16466020
TI  - [Rhabdomyolysis--causes, diagnostics, complications and treatment].

PMID- 16466021
TI  - A simple method for deprotection of the N- and O-carbobenzoxy groups and N
      methylation of the desosamine sugar moiety of ketolides. Application to the
      synthesis of ketolide analogues with various 9-iminoether moieties and their
      antibacterial activities.
AB  - A simple synthetic method for deprotection of the N- and O-carbobenzoxy groups
      (Cbz) of the desosamine sugar moiety of ketolides is reported. This deprotection
      method is applicable to the synthesis of a variety of ketolide analogues with
      various 9-iminoether moieties in good to moderate yield. Among the ketolide
      derivatives prepared by this method, compound 7g with a quinoline-6-yl moiety
      showed potent activity against erythromycin-resistant pathogens as well as
      Haemophilus influenzae.

PMID- 16466022
TI  - Isolation and structures of novel fungal metabolites as chemokine receptor (CCR2)
      antagonists.
AB  - The chemokine receptor, CCR2, is predominantly expressed on
      monocytes/macrophages, and on a subset of memory T cells. It binds to several CC
      type chemokines of the monocyte chemoattractant protein (MCP) family of which MCP
      1 exhibits the highest affinity. CCR2/MCP-1 expression/association in
      monocyte/macrophage/T cells has been associated with inflammatory processes such
      as rheumatoid arthritis, multiple sclerosis and atherosclerosis. Neutralization
      of CCR2 with either a peptide or receptor antagonist results in the prevention of
      joint swelling in rodent models of arthritis. In this paper, bioassay-guided
      discovery of CCR2 receptor antagonists derived from natural product extracts are
      reported. These antagonists belong to two main classes exemplified by
      bisthiodiketopiperazines and cytochalasins. Six compounds, including emestrin,
      two new emestrin analogs, and chaetomin represent the first group of compounds.
      These compounds inhibited the binding of MCP-1 to CCR2 (CHO membrane) with IC50
      values of 0.8 to 9 microM and exhibited good activity in a whole cell assay using
      MCP-1 and human monocytes with IC50's ranging from 4-9 microM. Cytochalasins A
      and B represented the second group and inhibited the binding activity with IC50
      values of 5 and 188 microM, respectively. This is the first report of natural
      product antagonists of the CCR2 receptor.

PMID- 16466023
TI  - Stemphones, novel potentiators of imipenem activity against methicillin-resistant
      staphylococcus aureus, produced by Aspergillus sp. FKI-2136.
AB  - A fungal strain FKI-2136 identified as genus Aspergillus was found to produce
      potentiators of imipenem activity against methicillin-resistant Staphylococcus
      aureus (MRSA). Two new compounds designated stemphones B and C were isolated
      along with a structurally related known compound cochlioquinone D from the
      fermentation broth of the producing strain by solvent extraction, silica gel
      column chromatography and preparative HPLC. These compounds have a common
      tetracyclic quinone skeleton. Stemphone C potentiated imipenem activity against
      the MRSA 512 fold by decreasing MIC value of imipenem from 16 microg/ml to 0.03
      microg/ml.

PMID- 16466025
TI  - Structure elucidation of new ascomycins produced by genetic engineering.
AB  - Three new ascomycins produced by genetic engineering of Streptomyces
      hygroscopicus ATCC 14891 have been purified and characterized. Replacement of the
      13-methoxyl group of ascomycin was accomplished by substitution of the
      corresponding acyltransferase domain of the polyketide synthase with a domain
      specific for either malonyl-CoA or methylmalonyl-CoA. The strain containing the
      methylmalonyl-specific acyltransferase domain produced a compound with properties
      consistent with those expected for 13-demethoxy-13-methylascomycin. NMR analysis
      revealed this material to be predominantly the cis amide rotamer, similar to
      ascomycin. The strain containing the malonyl-specific acyltransferase domain
      produced a mixture of two compounds, 13-demethoxyascomycin and the 9,14
      hemiacetal isomer of 13-demethoxyascomycin, in nearly equal amounts. NMR analysis
      revealed both compounds to be predominantly the trans amide rotamers.

PMID- 16466024
TI  - A new class of semisynthetic anthracycline glycoside antibiotics incorporating a
      squaric acid moiety.
AB  - Treatment of the squaric acid amide esters (7, 9) of anthracycline glycoside
      antibiotics with aliphatic and aromatic primary and secondary amines, amino
      acids, peptides and aminodeoxy sugars furnished the new asymmetric diamides 16
      19, 25-30, 32, 34 and 38-40 in stereoselective reactions which do not require
      protecting group-manipulations. The IC50 = 0.12 microM value measured for
      daunorubicin (1) on human leukemia (HL-60) cells is comparable to those obtained
      for the daunomycin-L-leucyl squaric acid diamide (30, IC50 = 0.18 microM) and the
      corresponding D-galactosamine derivative (40, IC50=0.22 microM).

PMID- 16466026
TI  - Nitrogen incorporation in the biosynthetic pathway of the nitrogen-containing
      polyketide, pamamycin in Streptomyces alboniger.
AB  - The biosynthetic pathway of pamamycin (1), a nitrogen-containing polyketide, was
      investigated using blocked mutants of Streptomyces alboniger. Hydroxy acids K
      (3), L (4) and S (5) were found in cultured materials of blocked mutants and the
      wild type strain, but no PM-ketone (2) was detected. Hydroxy acids 3, 4, 5 and de
      N-methylhydroxy acid L (7) were converted into 1, but 2 nor de-N-methylpamamycin
      (6) were not. We also confirmed that 3 and 7 were converted into 4. These results
      showed that an amino group was introduced into the carbonyl group of 3 by
      transamination, and subsequent N-methylation led to 4 in the pamamycin
      biosynthetic pathway. Quantitative analyses of hydroxy acid intermediates 3, 4,
      and 5, and pamamycin (1) suggested that transamination was the rate-determining
      step in pamamycin biosynthesis.

PMID- 16466027
TI  - Lichenicolins A and B, new bisnaphthopyrones from an unidentified lichenicolous
      fungus, strain LL-RB0668.
AB  - Lichenicolous fungus LL-RB0668 was isolated from a processed lichen thallus on a
      modified Lilly-Barnett solid medium. Two new bisnaphthopyrone compounds,
      lichenicolins A (1) and B (2), were isolated from the culture broth of this
      organism fermented on a rice-based solid medium. These results demonstrate that
      lichen-associated fungi potentially are a good resource for new bioactive natural
      products for current screening programs.

PMID- 16466028
TI  - New aldose reductase inhibitors N99-596 A and B from Streptomyces.
AB  - The actinomycete Streptomyces diannanensis, isolated from a soil sample collected
      in Yunnan province, China, was found to produce two novel isoflavone
      rhamnopyranosides, namely, 7,4'-dihydroxyisoflavone 3'-O-alpha-L-rhamnopyranoside
      (1) and 5,7,4'-trihydroxyisoflavone 3'-O-alpha-L-rhamnopyranoside (2). The
      structures of 1 and 2 were elucidated on the basis of extensive 1D and 2D NMR and
      MS spectral analyses. Compounds 1 and 2 exhibited in vitro activities against
      aldose reductase with an IC50 of 170 and 165 microM, respectively.

PMID- 16466029
TI  - Admitting defeat.

PMID- 16466030
TI  - SLC11A1 (formerly NRAMP1) gene polymorphisms and tuberculosis susceptibility: a
      meta-analysis.
AB  - OBJECTIVE: Although many case-control studies have investigated the association
      between the SLC11 A1 gene polymorphisms and tuberculosis (TB) susceptibility,
      results were conflicting due to limited power. We reviewed the literature
      systematically by means of meta-analysis, provided a quantitative summary
      estimate on the association with TB, and examined some sources of between-study
      heterogeneity. DESIGN: We searched databases (MEDLINE, PUBMED and OVID) from
      January 1995 to December 2004 using 'gene' or 'SLC11A1' or 'NRAMP1', in
      combination with 'tuberculosis', performed a manual search of citations from
      relevant original studies and review articles, or corresponded with authors.
      RESULTS: The summary ORs for studies with 3'UTR, D543N, INT4 and 5'(GT)n loci
      allele variants in the SLC11A1 gene were 1.33 (95%CI 1.08-1.63), 1.67 (95%CI 1.36
      2.05), 1.14 (95%CI 0.96-1.35) and 1.32 (95%CI 1.03-1.68), respectively, compared
      with their corresponding common alleles. The pooled ORs by sub-group analyses for
      the four loci described above were 1.20 (95%CI 0.86-1.68), 1.69 (95%CI 1.14
      2.50), 1.50 (95%CI 1.17-1.91), and 1.31 (95%CI 1.05-1.64) in subjects of African
      descent, 1.46 (95%CI 1.10-1.94), 1.65 (95%CI 1.29-2.12), 0.91 (95%CI 0.66-1.25)
      and 1.86 (95%CI 1.33-2.62) in Asian subjects, 1.81 (95%CI 0.66-4.93), 1.79 (95%CI
      0.72-4.47), 0.87 (95%CI 0.61-1.22) and 1.02 (95%CI 0.35-2.99) in European
      subjects. CONCLUSIONS: Polymorphisms at the four loci had no statistically
      significant association between the SLC11A1 variants and susceptibility to TB in
      subjects of European descent, while they showed a statistically significant
      association in Asian subjects (except the INT4 variant), African subjects (except
      the 3'UTR variant) and the population as a whole (except the INT4 variant).

PMID- 16466031
TI  - Adherence to anti-tuberculosis chemoprophylaxis and treatment in children.
AB  - SETTING: Limited data exist on adherence to anti-tuberculosis treatment and
      chemoprophylaxis in children in high-burden settings. OBJECTIVE: To determine the
      adherence to anti-tuberculosis chemoprophylaxis and treatment in children
      evaluated as household contacts of adult pulmonary tuberculosis (PTB) cases.
      METHODS: A retrospective study, conducted from January 1996 to September 2003, in
      suburban Cape Town, South Africa, with a high TB incidence. A folder search was
      done on all children <5 years of age identified as household contacts of adult
      PTB cases between 1996 and 2003. Data on screening for TB and adherence to
      prescribed therapy in child contacts were analysed. RESULTS: Three hundred and
      sixty-one contact episodes with 243 adult PTB cases were identified in 335
      children. The median age was 25 months. Adherence to anti-tuberculosis treatment
      was significantly better than adherence to chemoprophylaxis (82.6% vs. 44.2%; OR
      6.83; 95%CI 3.6-12.96). Adherence to a 3-month chemoprophylaxis regimen of
      isoniazid and rifampicin (3HR) was significantly better than adherence to a 6
      month chemoprophylaxis regimen of isoniazid only (69.6% vs. 27.6%; OR 4.97; 95%CI
      2.40-10.36). CONCLUSIONS: Although adherence to treatment was good, adherence to
      unsupervised chemoprophylaxis was poor. We recommend that shorter
      chemoprophylaxis regimens such as 3HR should be considered to improve adherence,
      but further studies are required.

PMID- 16466032
TI  - Treatment of latent tuberculosis in persons at risk for multidrug-resistant
      tuberculosis: systematic review.
AB  - SETTING: The emergence and spread of multidrug-resistant tuberculosis (MDR-TB),
      caused by Mycobacterium tuberculosis resistant to at least isoniazid (INH) and
      rifampicin, is a threat to global TB control. OBJECTIVE: To appraise evidence of
      the effectiveness of treatment of latent TB infection (LTBI) in people at risk
      for developing active MDR-TB. DESIGN: Systematic review of comparative studies of
      people treated and not treated for LTBI following exposure to MDR-TB. DATA
      SOURCES: PubMed, EMBASE, LILACS and the Cochrane Library (December 2004).
      RESULTS: Two observational studies met inclusion criteria. A prospective cohort
      study found individualised tailored treatment to be effective for preventing
      active TB in children (OR = 0.20, 95%CI 0.04-0.94), while a retrospective cohort
      study found INH not to be effective (OR = 0.46, 95%CI 0.07-2.32). CONCLUSION:
      Evidence of the effects of treatment of LTBI in people exposed to MDR-TB is
      extremely limited in both quantity and quality. The increasing global spread of
      MDR-TB and the difficulties in treating it emphasise the need for effective
      preventive measures. Ideally, this issue should be addressed in a randomised
      controlled trial. Until such a trial is conducted, routine clinical data
      collected as part of existing TB control programmes could be useful and can be
      generated relatively easily.

PMID- 16466033
TI  - Delayed tuberculosis diagnosis and tuberculosis transmission.
AB  - SETTING: Tuberculosis (TB) patients and their close contacts reported to the
      Maryland Department of Health and Mental Hygiene from 1 June 2000 to 30 November
      2001. OBJECTIVES: A recent prospective study found that 49% of pulmonary TB
      patients had total treatment delays > or = 90 days. This cohort was analyzed to
      determine the association between total treatment delay and TB transmission.
      DESIGN: TB patient data were collected as part of a prospective cohort study;
      contact data were collected from local health departments. RESULTS: Close
      contacts of 54 US-born patients (n = 310) and those of 70 foreign-born cases (n =
      393) received tuberculin skin tests (TSTs). Among contacts of US-born patients
      with a total treatment delay of > or = 90 days, 40% had positive TSTs vs. 24%
      contacts of patients with shorter delays (aOR 2.34; P = 0.03). Other patient
      factors associated with TST positivity among contacts of US-born cases were black
      race (aOR 3.03; P = 0.05), sputum smear positive for AFB (aOR 3.29; P = 0.01) and
      chest radiograph with cavitation (aOR 3.11; P = 0.01). No associations were
      observed between foreign-born patients and risk of TST positivity among their
      contacts. CONCLUSION: Among US-born patients, delay in TB diagnosis is associated
      with greater transmission of infection to contacts and could be used
      independently of other index patient factors to identify contacts at greatest
      risk of TB infection.

PMID- 16466034
TI  - Diagnosing smear-negative tuberculosis using case definitions and treatment
      response in HIV-infected adults.
AB  - OBJECTIVE: To assess the diagnostic utility of expanded case definitions for HIV
      associated smear-negative pulmonary tuberculosis (PTB) and extra-pulmonary TB
      (EPTB), and to derive objective criteria for response to anti-tuberculosis
      treatment. DESIGN: A prospective cohort study of HIV-infected adults who met
      expanded clinical case definitions for smear-negative PTB and EPTB. METHODS: All
      participants were started on rifampicin-based anti-tuberculosis treatment after
      mycobacterial cultures from multiple sites. At weeks 2, 4 and 8, response to
      treatment (RTT) was assessed by measuring changes in weight, haemoglobin, C
      reactive protein, Karnofsky performance score and symptom count ratio. RESULTS:
      Of 147 participants enrolled, 105 (71%) were diagnosed with definite (culture
      positive) or probable (histological features) TB and 25 (17%) with possible TB
      (treatment response). The positive predictive value for the most common case
      definitions ranged from 89% to 96%. Significant improvements in all the RTT
      parameters occurred in the subjects with confirmed TB (P < 0.001). Clinically
      relevant RTT criteria were derived, two or more of which were met at week 8 in
      97.5% of subjects with confirmed TB, 91.3% of subjects with possible TB and none
      of the subjects without TB. CONCLUSION: Expanded case definitions could enhance
      the diagnosis of PTB and EPTB in HIV-infected adults in resource-limited
      settings. Using objective criteria, RTT can be assessed within 8 weeks of
      initiating anti-tuberculosis treatment.

PMID- 16466035
TI  - Comparison of intermittent ethambutol with rifampicin-based regimens in HIV
      infected adults with PTB, Kampala.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) is a key factor responsible
      for the high rates of tuberculosis (TB) in sub-Saharan Africa. Treatment of TB
      with rifampicin (R, RMP) containing short-course regimens is highly effective in
      HIV-infected adults. We conducted a study to compare the efficacy and safety of
      intermittent ethambutol (E, EMB) with two RMP-containing regimens to treat
      pulmonary TB in HIV-infected patients. SETTING: National Tuberculosis Treatment
      Centre, Mulago Hospital, Kampala, Uganda. DESIGN: This was a prospective cohort
      compared to two non-randomised control groups. The study group and the two
      control arms were treated with 2 months of isoniazid (H), RMP, pyrazinamide (Z)
      and EMB followed by 6 E3H3 for the study group and 4HR or 6HR for controls.
      RESULTS: Between April 1993 and March 2000, 136 patients were enrolled in the
      2EHRZ/E3H3 arm, 147 in the 2EHRZ/4HR arm and 266 in the 2EHRZ/6HR arm. The
      relapse rate was 18.2 per 100 person-years observation (PYO) for the study
      regimen compared to 9.7/100 PYO (P = 0.0063) and 4.8/100 PYO (P = 0.0001) in
      patients treated with 2 EHRZ/4HR or 2EHRZ/6HR, respectively. CONCLUSION: The
      2EHRZ/6E3H3 regimen is safe and effective but has a significant risk of relapse.

PMID- 16466036
TI  - Treatment outcomes by drug resistance and HIV status among tuberculosis patients
      in Ho Chi Minh City, Vietnam.
AB  - OBJECTIVE: To assess the combined effects of drug resistance, HIV infection and
      treatment regimen on treatment outcomes of smear-positive tuberculosis patients
      in Ho Chi Minh City, Vietnam. METHODS: A representative sample of patients
      diagnosed in 1998-2000 in 12 urban districts was offered HIV testing and
      submitted sputum for Mycobacterium tuberculosis culture and drug susceptibility
      testing. New patients were treated with 2SHRZ/6HE in nine districts and with
      2SHRZ/4RH in three districts. RESULTS: The cure rate was 87% (1240/1430) among
      new patients compared to only 73% (287/391) among previously treated patients.
      Failure was associated with multidrug resistance (adjusted odds ratios [aOR] 49.6
      and 16.6, respectively) and combined resistance to isoniazid (INH) and
      streptomycin (SM) (aOR 13.4 and 4.8), but not with HIV infection. New patients
      had an increased risk of failure on treatment with 2SHRZ/4RH compared to
      2SHRZ/6HE if the isolate was resistant to INH and SM (aOR 2.8, P = 0.016). Death
      during treatment occurred in 15 of 50 HIV-infected patients (30%). Mortality was
      significantly associated with HIV infection (aOR 29.9), multidrug resistance (aOR
      4.7) and other resistance to two or more drugs (aOR 2.1). CONCLUSION: In Vietnam,
      adaptation of treatment regimens should be considered, and interventions are
      needed to reduce the high mortality among HIV-infected patients.

PMID- 16466037
TI  - Initial drug susceptibility profile of M. tuberculosis among patients under TB
      programme in South India.
AB  - SETTING: Pulmonary tuberculosis (PTB) patients enrolled for treatment at
      government health facilities in a sub-district of Thiruvallur district, Tamil
      Nadu, India. OBJECTIVES: To determine the drug susceptibility profile among PTB
      patients admitted to treatment according to the Revised National Tuberculosis
      Control Programme (RNTCP). METHODOLOGY: From May 1999 to December 2003, two
      additional sputum samples were collected from all patients at the start of anti
      tuberculosis treatment under DOTS and were transported to a central laboratory
      for Mycobacterium tuberculosis culture and drug susceptibility testing (DST).
      RESULTS: DST results were available for 1603 new sputum smear-positive patients;
      85% of patients had organisms fully susceptible to streptomycin (S), isoniazid
      (H) and rifampicin (R), 10.4% any resistance to H and 1.7% to HR. Of 443 patients
      with history of previous anti-tuberculosis treatment, 59% had organisms
      susceptible to S, H and R, 37% had any resistance to H and 11.7% to HR.
      CONCLUSION: The DST profile showed that the vast majority of patients have drug
      susceptible organisms, and that currently recommended regimens under the RNTCP
      would be effective in the treatment of TB.

PMID- 16466038
TI  - Prevalence of drug resistance under the DOTS strategy in Hyderabad, South India,
      2001-2003.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to
      at least isoniazid (INH) and rifampicin (RMP), is considered a threat to TB
      control. Implementation of DOTS ensures high cure rates and prevents MDR.
      OBJECTIVE: To study the prevalence of MDR-TB from a retrospective analysis of the
      data in a tuberculosis unit where DOTS was implemented over a period of 6 years
      through public private mix (PPM). METHODS: Drug susceptibility testing of
      Mycobacterium tuberculosis samples isolated from the cultures of newly registered
      and retreatment sputum smear-positive cases during 2001-2003. RESULTS: During the
      study, 909 sputum-positive cases were registered and analysed. Of these, 714 were
      new and 195 were retreatment sputum-positive cases. INH resistance was found in
      3.2% (23) of new and 9.2% (18) of retreatment cases. RMP resistance was present
      in 1.5% (11) of new and 7.2% (14) of retreatment cases. MDR was present only in
      0.14% (1) of new and 2% (4) of retreatment cases. New cases had cure rates of 96%
      compared to 85% in retreatment cases. CONCLUSION: The prevalence of MDR-TB is low
      where success rates are high.

PMID- 16466039
TI  - Nationwide study of drug resistance among acid-fast bacilli positive pulmonary
      tuberculosis cases in Lebanon.
AB  - OBJECTIVE: To assess the prevalence of drug resistance among smear-positive
      sputum specimens from pulmonary tuberculosis (TB) cases in Lebanon. DESIGN:
      Between July 2002 and April 2004, 224 newly diagnosed TB cases and 21 previously
      treated TB cases were collected nationwide. Mycobacterium tuberculosis isolates
      were tested against isoniazid (INH), rifampicin (RMP), streptomycin (SM) and
      ethambutol (EMB) using the BACTEC-TB system. RESULTS: M. tuberculosis and non
      tuberculous mycobacteria (NTM) isolates were recovered from 190 and 15 new cases,
      respectively, and from 16 and 1 previously treated cases, respectively. Overall
      drug resistance among new TB vs. previously treated TB cases was 19.5% and 75%,
      and for single drugs it was INH (12% vs. 63%), RMP (3% vs. 56%), SM (12% vs. 44%)
      and EMB (3% vs. 44%). The overall rate of multidrug resistance (MDR) was 5.8% (1%
      vs. 62.5%). The male:female ratio was 1.3:1; most were young adults. CONCLUSION:
      Relatively moderate single drug resistance and very low MDR rates were found
      among new TB cases, while among previously treated TB cases very high resistance
      and MDR resistance rates were detected. Such findings underline the need for
      ongoing stringent control measures to curb the spread of M. tuberculosis and its
      deleterious effects.

PMID- 16466040
TI  - Ethambutol resistance testing by mutation detection.
AB  - OBJECTIVE: To identify chromosomal mutations that confer resistance to ethambutol
      (EMB) in Mycobacterium tuberculosis. DESIGN: Drug-resistant (n = 235) and drug
      susceptible (n = 117) M. tuberculosis isolates collected from the Western Cape in
      South Africa were subjected to embB gene analysis and the results were compared
      to phenotypic EMB testing. RESULTS: Genotypic analysis identified mutations at
      codon 306 of the embB gene in 20% (47/235) of the resistant isolates in
      comparison to only 1.7% (4/235) of those that were phenotypically resistant to
      EMB by the agar diffusion method. No gene mutations were detected in susceptible
      isolates. Phenotypic retesting in BACTEC demonstrated that the 47 genotypically
      resistant isolates were phenotypically resistant to EMB. This implies that 91.4%
      (43/47) of EMB resistance had been phenotypically missed by routine laboratory
      procedures. EMB resistance was closely linked to multidrug resistance (MDR);
      87.2% (41/47) of the EMB-resistant isolates were resistant to both isoniazid and
      rifampicin. A newly developed one-step amplification refractory mutation system
      polymerase chain reaction (ARMS-PCR) method correctly detected the EMB-resistant
      genotype. CONCLUSION: Implementation of more accurate diagnosis of EMB resistance
      may enhance patient management in South Africa, as standardised treatment of MDR
      TB with second-line drugs is currently dependent on the outcome of the EMB
      resistance test.

PMID- 16466041
TI  - Influence of diabetes on manifestations and treatment outcome of pulmonary TB
      patients.
AB  - OBJECTIVE: To understand the influence of diabetes on the clinical and
      bacteriological aspects and treatment outcome of pulmonary tuberculosis (PTB)
      patients. SETTING AND DESIGN: Records of 692 consecutive smear-positive PTB
      patients admitted to a referral hospital in Riyadh, Saudi Arabia, were reviewed
      retrospectively. The characteristics of 187 patients with diabetes mellitus (PTB
      DM group) were compared to 505 patients without DM (PTB group). RESULTS: In the
      PTB-DM group, 65.2% of the patients had numerous acid-fast bacilli (AFB) on
      sputum smear examination compared to 54.1% in the control group (P = 0.008).
      Among new cases, PTB-DM patients had a lower prevalence of resistance to any anti
      tuberculosis drug (6.4% vs. 16.0%, P = 0.007) and achieved higher sputum
      conversion rates at the end of 3 months of treatment (98.9% vs. 94.7%, P =
      0.013). Favourable outcomes (cured/treatment completed), failure, death and
      default were comparable in both groups (P = 0.7005). CONCLUSIONS: PTB-DM patients
      have a higher pre-treatment bacillary load, a lower prevalence of anti
      tuberculosis drug resistance and achieve slightly higher sputum conversion by the
      end of 3 months of treatment compared to non-diabetic patients. The association
      of diabetes does not alter the final treatment outcome among PTB patients.

PMID- 16466042
TI  - An epidemiological evaluation of risk factors for tuberculosis in South India: a
      matched case control study.
AB  - SETTING: There are limited data on risk factors associated with tuberculosis (TB)
      in India. OBJECTIVES: To evaluate potential socio-demographic risk factors for
      TB. DESIGN: Matched case-control. Cases were all new diagnoses of pulmonary TB
      attending as out-patients at St John's Medical College Hospital, Bangalore,
      India, from October 2001 to October 2003. Age- and sex-matched controls, one for
      each case (n = 189), were recruited among relatives accompanying non-TB in
      patients in the hospital. RESULTS: Significant risk factors were low education
      level (OR 0.30; 95%CI 0.11-0.82), not having a separate kitchen (OR 3.26; 95%CI
      1.25-8.46) and chronic disease, mainly diabetes (OR 2.44; 95%CI 1.17-5.09). High
      income, cooking with biomass fuels, history of smoking and alcohol consumption
      were not significant on multivariate analysis. Patients were respectively 11 and
      seven times more likely to have a BMI <18.5 (95%CI 5.62-21.98) and mid-arm
      circumference <24 cm (95%CI 3.87-11.89). CONCLUSIONS: In our study, TB was
      associated with low education level, kitchen type and diabetes, reflecting the
      complex interaction between non-communicable disease, urbanisation and a changing
      economic climate in Bangalore. The relationship between TB, the use of biomass
      cooking fuels and gender differentials related to fuel exposure merit further
      exploration. The study underscores the poor nutritional status of patients.

PMID- 16466043
TI  - Prevalence of smear-positive pulmonary tuberculosis in a rural district of
      Ethiopia.
AB  - SETTING: A rural district in Southern Ethiopia. OBJECTIVE: To estimate the
      prevalence of smear-positive pulmonary tuberculosis (TB). DESIGN: In this cross
      sectional study, adults aged >14 years were surveyed by home-to-home visit, and
      asked about cough of > or = 2 weeks with or without sputum, chest pain or
      difficulty in breathing. Symptomatic suspects submitted three sputum samples for
      standard smear microscopy. RESULTS: Of 16697 adults surveyed, 436 (2.6%) were
      symptomatic and submitted sputum samples. Thirteen (3%) were positive for acid
      fast bacilli, and the prevalence of smear-positive TB was 78 per 100 000
      population (95%CI 36-120). Twenty-four smear-positive cases identified through
      the existing health care delivery were on anti-tuberculosis medication at the
      time of the survey. The ratio of smear-positive cases on treatment to those newly
      detected by the survey was 2:1. CONCLUSION: The prevalence of TB in this rural
      setting was unexpectedly low. For every two cases of smear-positive TB on
      treatment, there was one undetected infectious case in the community. However, as
      our screening technique did not allow detection of cases who did not report
      symptoms, the true prevalence may have been underestimated.

PMID- 16466044
TI  - Decentralising tuberculosis case management in two districts of Burkina Faso.
AB  - SETTING: In West Africa, national tuberculosis programmes (NTPs) face many
      problems due to the low performance of health care delivery systems and patients'
      social and cultural environment. OBJECTIVE: To improve the case management of TB
      in Burkina Faso. DESIGN: Using the operational research process as a tool, TB
      case management was decentralised from the district hospital to eight primary
      health care centres in 2003. RESULTS: Twelve months after decentralisation, the
      quality of case detection remained satisfactory. The delay between the
      identification of TB suspects with chronic cough and the confirmation of TB was
      reduced from 13 to 6 days. The detection rate of TB suspects during the study
      (30%) was twice as high as for 2001 and 2002 (15%). However, the detection rate
      for smear-positive TB cases decreased from 32.3% in 2001 and 2002 to 6.5% during
      the year of the study. CONCLUSION: Sufficient time and commitment are essential
      to obtain a case management system that is decentralised and effective. Efforts
      therefore need to continue to obtain more information and better results.

PMID- 16466045
TI  - CNS tuberculosis: a longitudinal analysis of epidemiological and clinical
      features.
AB  - In a prospective Canadian cohort of 82 764 patients with tuberculosis (TB), the
      risk of developing central nervous system manifestations of TB (CNS-TB) (1%) was
      higher among younger, female, Aboriginal and foreign-born persons (P < 0.005),
      together with an elevated mortality risk (RR 4.23), compared to controls with
      only pulmonary TB. TB detection was lower in the CNS-TB group (P < 0.005), while
      the likelihood of being cured was also reduced (P < 0.005). CNS-TB remains a
      serious complication of TB in the industrialised world.

PMID- 16466046
TI  - Implementation of asthma guidelines in health centres of several developing
      countries.
AB  - SETTING: Nine selected out-patient clinics caring for asthma patients in Algeria,
      Guinea, Ivory Coast, Kenya, Mali, Morocco, Syria, Turkey and Vietnam. DESIGN:
      Prospective enrolment of consecutive patients considered by the practitioner to
      have asthma with evaluation of adherence of the practitioner with recommended
      standard case management, including proportion of patients confirmed to have
      asthma, proportion in whom severity was correctly graded and proportion in whom
      treatment with inhaled corticosteroids corresponded to severity grade. RESULTS:
      Of 499 consecutive patients, 456 (91%) were enrolled and evaluated. The diagnosis
      was confirmed in 263 (58%). Agreement between the practitioner and the guidelines
      in assigning grade of severity was moderate overall (kappa = 0.42). It was higher
      for assignment of grade using symptoms (K = 0.51), but poor for assignment of
      grade using peak expiratory flow (PEF) rate (kappa = 0.29), with practitioners
      tending to underestimate the severity. Agreement between the practitioners'
      assessment of severity and treatment with inhaled corticosteroids was poor (kappa
      = 0.18), with underutilisation of inhaled corticosteroids. CONCLUSIONS:
      Practitioners caring for asthma patients in this study tended to underutilise the
      PEF rate in assessing their patients and underutilised treatment of patients with
      inhaled corticosteroids.

PMID- 16466047
TI  - Factors related to variability in long-term oxygen therapy prevalence.
AB  - OBJECTIVE: To analyse the variability of long term oxygen therapy (LTOT)
      prevalence according to several organisational and population factors. METHODS:
      Prospective multicentre survey in 29 public hospitals (population 6,796,964)
      recording data on the organisational structure of the participating centres and
      factors related to LTOT prevalence. Official figures were also obtained from
      local health authorities on the prevalence and cost of LTOT. RESULTS: The overall
      prevalence of LTOT was 184 per 100000 population (range 71-473). There was a
      specific unit or staff member for LTOT supervision in 17 (58.6%) centres, giving
      a lower prevalence (169 vs. 237/ 100000; P = 0.03). The altitude of the
      participating centres (median 92 m, mean 275 m; range 4-848 m) was found to
      influence LTOT prevalence (r = 0.73; P = 0.005). In the linear regression
      analysis, the coefficient of determination for altitude was 0.504. Other factors,
      such as percentage of population aged over 65 years, the attitude of prescribers
      towards patients with low adherence, current smokers or those with a PaO2 = 61
      mmHg, were not related to LTOT prevalence. CONCLUSIONS: Altitude and the
      existence of a specific unit or staff member for LTOT supervision significantly
      influence LTOT prevalence.

PMID- 16466048
TI  - Relationship of ARTI to incidence and prevalence of tuberculosis in a district of
      south India.
AB  - OBJECTIVE: To validate the currently used empirical relationship between annual
      risk of tuberculous infection (ARTI) and incidence and prevalence of smear
      positive cases. SETTING: Two disease surveys to estimate the prevalence and
      incidence of tuberculosis (TB) among adults in Tiruvallur district, south India,
      and a tuberculin survey to estimate the ARTI among children. RESULTS: The
      incidence of TB was estimated to be 82 and prevalence 210 per 100,000 population
      and ARTI 1.6%. We estimated that 1% ARTI corresponded to 51 new and 131 prevalent
      cases. CONCLUSION: The currently used empirical relationship between ARTI and
      incidence can be used by programme managers as an effective monitoring tool.

PMID- 16466049
TI  - A rose is a rose: but what about Pneumocystis pneumonia?

PMID- 16466050
TI  - Management of tuberculosis in children in low-income countries.
AB  - Children become infected when they are exposed to infectious adults with smear
      positive tuberculosis (TB). Most children become infected, but few progress to
      disease (TB). Children at greatest risk of developing disease are those younger
      than 5 years of age, HIV-infected and severely malnourished. TB is diagnosed in a
      child when the child has been exposed to an infectious case, has symptoms and a
      radiological picture suggestive of TB. Children are treated by the DOTS strategy,
      and can be treated with 6- or 8-month regimens. HIV-infected children are treated
      with the same regimens. Children under 5 years of age exposed to an infectious
      case or infected with TB (tuberculin skin test positive) who are asymptomatic
      must receive preventive chemotherapy (isoniazid for 6 months). Babies born to
      mothers with active TB must be managed carefully, as they could have congenital
      TB, and if they do not have TB they will need preventive chemotherapy for 6
      months. BCG is indicated in all children soon after birth, except for those with
      symptomatic HIV infection. The main aim of any TB programme is to prevent the
      spread of TB, and also the spread to children, which is best achieved by early
      detection and treatment of adults with smear-positive TB.

PMID- 16466051
TI  - The burden of childhood tuberculosis: a public health perspective.
AB  - The burden of childhood tuberculosis (TB) reflects recent transmission within a
      community and the level of TB control achieved within the adult (maintenance
      host) population. Children contribute little to the maintenance of the TB
      epidemic, but they may suffer severe TB-related morbidity and mortality. This
      review describes the main determinants of the burden of childhood TB within a
      particular community. Basic infectious disease principles identify the community,
      and not the individual, as the central entity that sustains an epidemic. The
      prevalence of TB is determined by the community's exposure to Mycobacterium
      tuberculosis, and their vulnerability to developing disease following exposure.
      The main variables that influence both exposure and vulnerability are discussed.
      Multiple variables are linked to poverty, and it is their cumulative effect,
      rather than the exact degree of poverty, that seems most important. Diligent
      contact tracing and the use of preventive chemotherapy will reduce the TB-related
      suffering of children. The burden of childhood TB, however, is a reflection of
      our ability to control the epidemic; this remains the ultimate challenge. Current
      efforts to control the TB epidemic aim to reduce transmission by treating sputum
      smear-positive adults, while very little emphasis is placed on reducing the
      vulnerability of high-burden communities. Successful control of the epidemic is
      the most effective way to reduce the burden of childhood TB, but this will
      require a holistic approach that acknowledges the importance of sustainable
      poverty alleviation.

PMID- 16466052
TI  - Molecular epidemiology of Mycobacterium tuberculosis in China: a nationwide
      random survey in 2000.
AB  - OBJECTIVE: To determine the contribution of the Mycobacterium tuberculosis (TB)
      Beijing genotype to the population structure of M. tuberculosis complex in China.
      DESIGN: Genotypes of 441 mycobacterial isolates were determined by spoligotyping
      and IS6110 restriction fragment length polymorphism (RFLP). The isolates were
      from a nationwide random survey for the epidemiology of TB conducted in 2000, and
      the drug susceptibility patterns and epidemiological data were known. RESULT: A
      total of 408 samples contained M. tuberculosis as determined by spoligotyping. Of
      the M. tuberculosis strains, 64.9% (265/408) were of the Beijing genotype. Using
      the chi-squared test, no statistically significant differences were observed in
      the proportion of Beijing genotype TB in patients of different sex, age or living
      in different areas of the country, but a significant difference was observed with
      multidrug-resistant (MDR) TB: 77.8% (42/ 54) of MDR isolates were of the Beijing
      genotype vs. 60.2% (213/354) of the drug-susceptible isolates. In the
      multivariate logistic regression model, the Beijing genotype was significantly
      associated with region and not with MDR. CONCLUSION: The M. tuberculosis Beijing
      genotype has prevailed in China for at least five decades and is associated with
      region.

PMID- 16466053
TI  - Socio-demographic and geographic indicators and distribution of tuberculosis in
      Hong Kong: a spatial analysis.
AB  - OBJECTIVE: To determine the socio-demographic and geographic indicators
      responsible for the distribution and transmission of tuberculosis (TB) in Hong
      Kong using geographical information system (GIS) technology. MATERIALS AND
      METHODS: All patients with bacteriologically proven TB over a period of 3 years
      (May 1999-April 2002) residing within Hong Kong Island were studied. Molecular
      characterisation of their sputum isolates by IS6110-based restriction fragment
      length polymorphism (RFLP) technique was performed. Socio-demographic data were
      derived from the 2001 Hong Kong population census. Geographic coordinates of
      patients' addresses were linked to the GIS; large street block groups (LSBGs)
      were the units of analysis. RESULTS: Of 2387 patients with bacteriologically
      confirmed TB, 2332 had valid addresses distributed in 430 LSBGs in Hong Kong
      Island. Of the five socio-demographic indicators studied, significant
      correlations were found between the rate of TB in an LSBG and low educational
      attainment, elderly population and low-income household, but not population
      density or unemployment. The five socio-demographic indicators were not different
      between LSBG with clustered cases and those with unique cases. CONCLUSION: Low
      educational attainment, old age and poverty were significant determinants of the
      rate of TB in different parts of Hong Kong, while none of the socio-demographic
      indicators was related to disease transmission.

PMID- 16466054
TI  - Antibody response to four secretory proteins from Mycobacterium tuberculosis and
      their complex antigen in TB patients.
AB  - OBJECTIVE: To evaluate antibody responses to a panel of four protein antigens
      secreted from Mycobacterium tuberculosis, CFP-21, ESAT-6, MPT-63 and MPT-64, and
      their complex antigen. DESIGN: Seventy-eight samples of serum and cerebral spinal
      fluid were tested by ELISA. RESULTS: Serum IgM antibody positive rates of protein
      antigens CFP-21, ESAT-6, MPT-63 and MPT-64 and their multi-antigen complex were
      respectively 34.6%, 60.3%, 52.6%, 78.2% and 96.2%; IgG antibody positive rates
      were respectively 46.2%, 64.1%, 93.6%, 57.7% and 84.6%. The specificity of the
      antibodies to the four proteins secreted from M. tuberculosis and its mixture
      antigen was 100%; sensitivity to the multi-antigen complex was higher than for
      the four single antigens. Among the IgM positive rates, the differences between
      the multi-antigen complex and CFP-21, ESAT-6, MPT-63 and MPT-64 were significant
      (P < 0.01); among the IgG positive rates, the differences between the multi
      antigen complex and CFP-21, ESAT-6 and MPT-64 were significant (P < 0.01).
      Although the IgG positive rate for MPT-63 was higher than for the multi-antigen
      complex, the difference was not significantly different (P > 0.05). CONCLUSION:
      These findings indicate that the multi-antigen complex composed of CFP-21, ESAT
      6, MPT-63 and MPT-64 may be useful in the diagnosis of TB.

PMID- 16466055
TI  - A multicenter evaluation of tuberculin skin test positivity and conversion among
      health care workers in Brazilian hospitals.
AB  - SETTING: Four general Brazilian hospitals. OBJECTIVE: To assess the occupational
      risk of Mycobacterium tuberculosis (TB) in participating hospitals. DESIGN: In
      phase one of this longitudinal study, a cross-sectional survey documented
      baseline tuberculin skin test (TST) positivity rates. In phase two, TST
      conversion rates were evaluated in participants with an initial negative two-step
      TST. TST conversion data were analyzed to determine risk factors for TB infection
      using an increase of > or = 10 mm compared to baseline TST. RESULTS: The initial
      TST positivity rate was 63.1%; the follow-up TST conversion rate was 10.7 per
      1000 person-months (p-m). Hospital of employment, recent bacille Calmette-Guerin
      (BCG) vaccination, nosocomial TB exposure, and employment as a nurse were
      independent risk factors for TST conversion. Hospitals without TB infection
      control measures had higher conversion rates than those with control measures
      (16.0 vs. 7.8/ 1000 p-m, P < 0.001). CONCLUSIONS: This study indicates an
      important occupational risk of infection in health care settings with a high TB
      incidence. Longitudinal TST studies are a valuable tool to assess the
      occupational risk of TB, even in BCG-vaccinated populations, and should be used
      to direct limited resources for infection control.

PMID- 16466056
TI  - In closely monitored patients, adherence in the first month predicts completion
      of therapy for latent tuberculosis infection.
AB  - BACKGROUND: Current therapy for latent TB infection (LTBI) is long, and requires
      close follow-up. This results in sub-optimal adherence-the major reason for
      failure of therapy. METHODS: In an open label randomised trial comparing 4 months
      of rifampicin with 9 months of isoniazid, the proportion and regularity of doses
      taken, measured with an electronic monitoring system (MEMS), and provider
      estimates of adherence in the first month of therapy, were assessed as predictors
      of treatment completion. RESULTS: Of 104 patients analysed, 86 took more than 80%
      of doses within the expected interval, 11 took more than 80% of doses but over a
      longer time interval than usually allowed, and seven did not complete treatment.
      Treatment completion was associated with the number of doses taken, and the
      variability of intervals between doses during the first month of treatment.
      CONCLUSIONS: Adherence in the first month, based on the number of doses and
      variability of times when taken, could be useful to predict completion of LTBI
      therapy. Interventions could be targeted to patients with suboptimal adherence in
      the first month.

PMID- 16466057
TI  - Risk factors for defaulting from tuberculosis treatment: a prospective cohort
      study of 301 cases in the Gambia.
AB  - SETTING: An urban tuberculosis (TB) clinic, The Gambia. OBJECTIVE: To identify
      patient characteristics associated with increased rates of defaulting from
      treatment, specifically knowledge and cost factors amenable to intervention.
      DESIGN: Prospective cohort study of TB cases at least 15 years of age commencing
      treatment, interviewed by semi-structured questionnaire and followed for
      attendance at thrice-weekly directly observed treatment (DOT). RESULTS: Of 301
      patients, 76 (25.2%) defaulted from treatment and 25 did not return for
      treatment. The defaulting rate was higher among those who said they were
      uncertain that their treatment would work (HR 3.64; 95%CI 1.42-9.31, P = 0.007)
      and among those who incurred significant time or money costs travelling to
      receive treatment (HR 2.67; 95%CI 1.05-6.81; P = 0.04). These factors had
      differing effects with respect to time: uncertainty over treatment success was
      important in the first 90 days of treatment, while increased cost of travelling
      to the clinic was important after 90 days. CONCLUSION: In The Gambia, risk groups
      for defaulting can be recognised at the start of treatment and are at highest
      risk at different times. Home-based self-administration of medications after 3
      months of DOT should be considered as confidence in treatment success rises, and
      the costs of travelling to receive treatment start to take their toll.

PMID- 16466058
TI  - Barriers to effective tuberculosis control: a qualitative study.
AB  - SETTING: Emilia Romagna region, Italy. OBJECTIVE: To explore chest and infectious
      disease physicians' views of barriers to effective tuberculosis (TB) control and
      possible solutions. DESIGN: A series of nine focus groups including a total of 49
      physicians. RESULTS: Three categories of barriers to effective TB control were
      identified: 1) uncertainty about appropriate clinical practice in the treatment
      of specific sub-groups of patients, such as the elderly or immigrants; 2)
      organisational factors, such as the availability of diagnostic services and of
      sufficient resources; and 3) multiple barriers to a viable and effective TB
      control programme in a country with a low prevalence of TB. CONCLUSIONS: The lack
      of integration and coordination of health services, as well as the scarcity of
      dedicated TB nurses, were perceived by the participants as crucial barriers to
      effective TB control. As a result of this study, a regional programme was started
      with the goals of quantifying the need for TB nurses and developing a better
      network for required health services. Qualitative studies such as this can be
      useful in improving TB control in a low-prevalence TB country, to identify
      problems and increase the participation of key professionals.

PMID- 16466059
TI  - Relationship between quality of life and characteristics of patients hospitalised
      with tuberculosis.
AB  - SETTING: Ataturk Lung Diseases and Chest Surgery Hospital in Ankara, Turkey.
      OBJECTIVE: To determine the relationships between differences in socio
      demographic and family characteristics and changes that occur within the family
      and social environment in hospitalised patients with tuberculosis (TB) and levels
      of quality of life (QOL). DESIGN: TB in-patients were interviewed using a
      structured questionnaire and a QOL instrument. RESULTS: Findings indicated that
      the patients had a lower QOL level, and that those with low levels of education,
      no social insurance coverage and insufficient housing conditions had lower QOL
      scores. Patients who experienced negative changes in family life and social
      environment had lower QOL levels. CONCLUSION: Diagnosis, changes in family life
      and social milieu, the illness process and beliefs about the illness have diverse
      affects on the QOL of TB patients.

PMID- 16466060
TI  - Using e-mail in the management of tuberculosis patients, north-west Russia.
AB  - SETTING: Ten health care institutions in north-west Russia. OBJECTIVE: To improve
      the management of tuberculosis patients using e-mail. DESIGN: Over an 18-month
      period, all outgoing and incoming e-mails at the Arkhangelsk Regional
      Tuberculosis Centre were saved and categorised. All e-mails relating to distance
      learning were logged, and a consensus panel discussed and answered questionnaires
      regarding 47 e-mail-based second opinions. RESULTS: e-mail was found to speed up
      communication and increase the availability of specialist advice. Distance
      learning was positively received, but was used in moderation. For six of 47
      consultations (13%), the consensus panel deemed that fast access to a second
      opinion saved lives. In 30 consultations (64%), the patient was saved a round
      trip to a specialist centre. In 24 consultations (51%), the panel considered that
      the patients had started correct treatment between 1 week and 1 month earlier
      than without e-mail access. In 11 of these consultations, 23% of the total, the
      patient was found to be infectious. The learning effects of second opinions were
      recognised. CONCLUSION: General e-mail use and the second opinion service in
      particular were found to be useful. Further studies are needed to investigate the
      advantages and disadvantages of using e-mail as a tool in the management of TB.

PMID- 16466061
TI  - A randomised controlled trial of oral zinc on the immune response to tuberculosis
      in HIV-infected patients.
AB  - SETTING: The National HIV Unit, Singapore. OBJECTIVE: To test whether zinc
      supplementation improves the immune response to tuberculosis in HIV-positive
      patients. DESIGN: A double-blind, randomised, placebo-controlled trial of 28 days
      of oral zinc sulphate (50 mg of elemental zinc) or placebo in stable adult HIV
      positive patients receiving antiretroviral therapy with a CD4 count <200
      cells/microl. METHODS: IFN-gamma response to mycobacterial antigen stimulation,
      CD4/8 cell count, lymphocyte subsets, T-cell receptor excision circle (TREC)
      levels and viral load were measured at baseline and day 28. RESULTS: Thirty-two
      patients received zinc and 34 placebo. There was no significant change in the IFN
      gamma response to human PPD stimulation in the zinc or placebo groups (placebo
      baseline: 0.42 +/- 1.03, day 28: 0.84 +/- 1.21 IU/ml, zinc baseline: 1.26 +/-
      2.41, day 28: 1.39 +/- 1.88 IU/ml, P = 0.31 between groups), nor any of the other
      mycobacterial antigens tested. There were no changes in absolute CD4/8 cell
      levels or other lymphocyte subsets, TREC or viral load. Baseline zinc levels were
      normal in 62/66 (93.9%) patients. CONCLUSIONS: We found no evidence for
      recommending pharmacological supplementation with oral zinc in HIV-positive
      patients without zinc deficiency.

PMID- 16466062
TI  - Influence of treatment and immunological recovery on tuberculosis relapses in HIV
      infected patients.
AB  - SETTING: Studies on tuberculosis (TB) relapse in HIV-infected patients show
      contradictory results regarding the optimal duration of treatment. OBJECTIVE: To
      assess the incidence of TB relapse and associated factors in HIV-infected
      patients receiving a 9-month tuberculostatic regimen and concomitant HAART.
      PATIENTS AND METHODS: Observational prospective study recording 156 episodes of
      TB in 137 patients, most of whom were on a 9-month regimen of daily isoniazid and
      rifampicin-based TB treatment. The primary outcome measure was relapse after
      completion of therapy. RESULTS: Forty episodes were excluded due to death or loss
      to follow-up. The median follow-up was 24 months. Twenty-seven episodes of TB
      relapse were observed in 22 patients, yielding a relapse rate of 1.9/100 patient
      years in those on a regimen of > or = 9 months. A high recurrence rate was
      observed in those who had prematurely suspended treatment. Treatment duration >
      or = 9 months and achieving both an undetectable viral load and increasing CD4
      cell counts with HAART were associated with the absence of TB relapses.
      CONCLUSIONS: Considering its safety and tolerance, our results suggest that a 9
      month regimen would be recommendable in patients with severe immunosuppression
      until the optimal duration of TB treatment in HIV-infected patients has been
      defined in a randomised clinical trial including HAART.

PMID- 16466063
TI  - A registry of tuberculous meningitis in Hong Kong.
AB  - BACKGROUND: A prospective observational study of the presentation, diagnosis,
      treatment and outcome of tuberculous meningitis (TBM). METHODS: Demographic
      characteristics, clinical information, treatment and progress of TBM patients
      were followed. Their outcomes were ascertained every 6 months for 3 years after
      diagnosis. Prognostic factors associated with death or full recovery were
      examined using multivariate Cox's and logistic regression models, respectively.
      RESULTS: Between 1993 and 2000, 166 TBM patients were recruited. Their mean age
      was 42.9, 153 were Chinese and 81 were males; 92% received HRZS (H = isoniazid; R
      = rifampicin; Z = pyrazinamide; S = streptomycin), HRZE (E = ethambutol) or
      HRZES. Steroids were given to 105 patients, with no significant effect on
      outcome. After 3 years of follow-up, 110 patients had completely recovered, 20
      survived with disability and 26 died. Death was significantly associated with
      older age, lower cerebrospinal fluid (CSF) lymphocyte and poorer consciousness
      levels at the time of presentation, while full recovery was associated with
      younger age, being female and absence of complications. CONCLUSIONS: Relatively
      good outcomes of TBM cases were documented in this Hong Kong study with a case
      fatality ratio of 15.7% (26/166) up to 3 years. Early recognition, diagnosis and
      administration of effective treatment regimens were probably the most important
      factors in reducing mortality and morbidity.

PMID- 16466064
TI  - Bovine tuberculosis in Burdur, southern Turkey: epidemiological, pathological and
      economic study.
AB  - SETTINGS: Burdur is the most important dairy cattle breeding and milk production
      area of Turkey, and Burdur slaughterhouse is one of the biggest slaughterhouses
      in the southern part of the country. No scientific information is available on
      the prevalence of tuberculosis (TB) in cattle in Burdur. A survey was therefore
      undertaken to determine the prevalence of disseminated TB infection in cattle in
      this district. OBJECTIVES: To implement a disease monitoring system in Burdur
      slaughterhouse to estimate the annual prevalence of disseminated TB in cattle
      slaughtered and inspected in 2003-2004. DESIGN: Epidemiological survey. RESULTS:
      Prevalence of bovine TB was investigated in Burdur slaughterhouse from January
      2003 to December 2004. All of the affected animals were Holstein breed. The
      prevalence of disseminated TB in all slaughtered cattle was 0.38% in this period.
      The value of the condemned meat and organs was calculated to establish economic
      loss. CONCLUSION: Despite a strict eradication programme, bovine TB is still an
      important health issue among cattle and remains one of the greatest threats to
      cattle and human health in southern Turkey. Veterinarians and cattle producers in
      this region are encouraged to develop and work on herd plans aimed at controlling
      and eradicating TB.

PMID- 16466066
TI  - Application of the Capilia TB assay for culture confirmation of Mycobacterium
      tuberculosis complex isolates.
AB  - The usefulness of a low-tech rapid test for culture confirmation of Mycobacterium
      tuberculosis complex, Capilia TB, was tested on 172 mycobacteria-positive
      clinical samples. The overall sensitivity and specificity were 92.4% and 100%,
      respectively. In three of nine false-negative isolates a mutation in the mpb64
      gene could be detected.

PMID- 16466065
TI  - Questionnaire on health systems and national resources for control of respiratory
      health in low-income countries.
AB  - BACKGROUND: Due to increased exposure to risk factors such as ageing and tobacco
      smoking, chronic respiratory diseases (CRDs) have become a major cause of
      morbidity and mortality worldwide. Data on CRDs and their management in
      developing countries (DC) are nevertheless sparse and not comparable. OBJECTIVE:
      To implement and validate a standardised self-administered questionnaire to be
      proposed to health authorities to assess the resources of their health system for
      dealing with respiratory diseases. METHODS: The questionnaire concerned social
      security, description of the health system, human resources available within the
      system, initial training and continuing education of health personnel, existence
      of a list of essential drugs, vaccine coverage and specific resources involved in
      CRD and tobacco control. RESULTS: The validity of the criteria of the
      questionnaire was tested in Reunion Island, where health data are accessible and
      reliable, and was found to be satisfactory. Its acceptability and relevance were
      deemed appropriate in Tunisia and in Mozambique. CONCLUSION: The self
      administered questionnaire is a simple, reliable and cheap tool. Although
      designed for the study of respiratory diseases, it can easily be transposed and
      adapted to other pathologies.

PMID- 16466067
TI  - Development of a competitor DNA template of the 38 kDa gene for molecular
      quantification of M. tuberculosis.
AB  - The molecular quantification of Mycobacterium tuberculosis (TB) from clinical
      samples can improve the management of TB. Competitive polymerase chain reaction
      (C-PCR) is an accepted technique often used for this purpose, and IS6110 is the
      most popular target in such studies. As the number of these elements varies from
      0 to 16 in clinical isolates, it is prone to give inconsistent results. A simple
      PCR-based approach is described in this study to generate a novel competitor for
      a single copy 38 kDa gene for the development of C-PCR for the quantification of
      the M. tuberculosis genome.

PMID- 16466068
TI  - Rotavirus immunization again! It's important!

PMID- 16466069
TI  - Use of generics only for medication names hinders readers' understanding.

PMID- 16466070
TI  - A 5-year-old girl with fever, vomiting, abdominal pain.

PMID- 16466071
TI  - A 15-month-old boy with macrocephaly.

PMID- 16466072
TI  - Clinical and epidemiological aspects of rotavirus infection.
AB  - Rotavirus is a major worldwide cause of infant morbidity and mortality, and
      disease burden in the US is substantial. Vaccination is the only practical way to
      gain control over rotavirus disease. Prevention through the universal use of
      improved live oral vaccines is on the horizon.

PMID- 16466073
TI  - RotaTeq: a pentavalent bovine--human reassortant rotavirus vaccine.

PMID- 16466074
TI  - Rotarix: development of a live attenuated monovalent human rotavirus vaccine.

PMID- 16466075
TI  - RotaShield: the ill-fated rhesus-human reassortant rotavirus vaccine.

PMID- 16466076
TI  - Physicians' knowledge and attitudes about rotavirus gastroenteritis and rotavirus
      vaccine.
AB  - The morbidity and mortality associated with rotavirus gastroenteritis are
      significant. Despite the past safety concerns with RotaShield, many physicians
      believed the need for rotavirus vaccination remains. Although most physicians
      were not aware of specific rotavirus gastroenteritis disease burden statistics,
      they perceive rotavirus gastroenteritis to pose a serious risk for children for
      which a vaccine would be beneficial. Proof of safety and efficacy, an
      ACIP/AAP/AAFP recommendation, and private insurance coverage/reimbursement were
      critical features that would allow physicians to overcome barriers to the
      adoption of a new rotavirus vaccine.

PMID- 16466078
TI  - Gender differences in amino acid use during endurance exercise.
AB  - There are gender differences in the substrate used to fuel prolonged physical
      activity. Males rely on carbohydrate and amino acids (97%), while females use
      predominantly fat (62%) to fuel endurance exercise. This review looks at the
      mechanisms that regulate these gender differences, with a focus on amino acid
      metabolism. Gender-selective nutritional recommendations are indicated for
      physically active individuals and some cardiac patients who engage in intense
      aerobic activity.

PMID- 16466077
TI  - Effects of saccharides on brain function and cognitive performance.
AB  - This review outlines a role for saccharides in the brain and offers predictions
      about how saccharides might influence cognitive performance. Animal studies
      provide a biological mechanism by which saccharides affect brain function and, in
      turn, cognition. Furthermore, recent intervention studies suggest that
      saccharides may have an effect on the cognitive performance of humans. Because
      the effects of saccharide supplementation on cognitive performance are likely to
      be subtle, future investigations will face various methodological challenges, not
      the least of which is the need for sensitive outcome measures.

PMID- 16466079
TI  - Eating disorder in a hemodialysis patient: case report.
AB  - Renal replacement therapy may encourage eating disorders in some patients.
      Hemodialysis requires patients to attend dialysis sessions three times per week,
      during which time they are weighed pre- and post-treatment, so the importance of
      limiting "fluid weight" gains to prevent fluid overload and elevated blood
      pressure are constantly reinforced by the dialysis team. Patients must also
      follow rigorous therapeutic dietary modifications to prevent the buildup of urea
      and harmful waste products between treatments. This is a case report of a 30-year
      old man receiving renal replacement therapy who had anorexia nervosa of the
      bulimic subtype.

PMID- 16466080
TI  - Chocolate and cardiovascular health: is it too good to be true?
AB  - Recent findings indicate that cocoa and chocolate, when processed appropriately,
      may contain relatively large amounts of flavonoids, particularly catechin and
      epicatechin. We review the benefits of these flavonoids, specifically with regard
      to cardiovascular health, and raise several unresolved issues that suggest the
      need for additional research and product development in this area.

PMID- 16466081
TI  - Importance of pre-pregnancy and pregnancy iron status: can long-term weekly
      preventive iron and folic acid supplementation achieve desirable and safe status?
AB  - Most women worldwide enter pregnancy without adequate iron reserves or are
      already iron deficient. Estimates of iron needs during pregnancy are markedly
      reduced when iron reserves are available. The needs of absorbed iron to correct
      mild to moderate anemia in the last two trimesters are estimated. Pre-pregnancy
      and prenatal weekly supplementation can improve iron reserves effectively and
      safely, preventing excess iron and favoring better pregnancy outcomes. We explain
      how the weekly supplementation idea was developed, why current hemoglobin norms
      may be inadequately high (especially in pregnancy), and why excess iron as
      recommended by many agencies for developing populations can be undesirable.

PMID- 16466082
TI  - Effectiveness of weekly iron-folic acid supplementation to prevent and control
      anemia among women of reproductive age in three Asian countries: development of
      the master protocol and implementation plan.
AB  - The master protocol for studying the impact and process of implementation of
      weekly iron-folic acid supplementation under program conditions is described.
      Pilot projects guided by the protocol were carried out in the Philippines,
      Vietnam, and Cambodia, where anemia rates are high and different socioeconomic
      and cultural conditions exist. Each country utilized the same supplement but
      adapted implementation processes to their specific conditions. Social marketing
      and community mobilization were considered to be essential tools for
      sustainability.

PMID- 16466083
TI  - Implementing preventive iron-folic acid supplementation among women of
      reproductive age in some Western Pacific countries: possibilities and challenges.
AB  - Lack of effective implementation mechanisms is identified as a major obstacle in
      the prevention and control of iron-deficiency anemia. This paper discusses
      experiences gained from implementing iron-folic acid supplementation in the
      Philippines, Vietnam, and Cambodia. The understanding of contextual elements is
      proposed as a foundation for planning interventions. Moreover, it is suggested
      that a social marketing framework should provide a way of thinking about how to
      influence related behaviors. The application of a social marketing framework
      applied using a "5 P's" approach: public relations and collaboration, product,
      price, place, and promotion, is described, as well as enabling factors
      (possibilities) and inhibiting factors (challenges) of this approach. Although a
      program to improve iron nutrition among women of reproductive age may not be
      simple to implement, it is essential to enhancing health, human development, and
      economic advancement in developing countries.

PMID- 16466084
TI  - Community mobilization and social marketing to promote weekly iron-folic acid
      supplementation: a new approach toward controlling anemia among women of
      reproductive age in Vietnam.
AB  - Community-based social marketing and mobilization increased knowledge and
      participation in preventive weekly iron-folic acid supplementation among women of
      reproductive age in Vietnam. Rates of buying and taking the weekly supplement
      containing 60 mg elemental iron and 3.5 mg folic acid among non-pregnant women of
      reproductive age was between 55% and 92%. Free distribution to pregnant women of
      the weekly supplement containing 120 mg iron and 3.5 mg folic acid covered almost
      all pregnant women during the project. In developing countries where community
      women's groups and health networks are strong, preventive supplementation can be
      successfully promoted to encourage active participation in the prevention and
      control of iron-deficiency anemia.

PMID- 16466085
TI  - Community mobilization and social marketing to promote weekly iron-folic acid
      supplementation in women of reproductive age in Vietnam: impact on anemia and
      iron status.
AB  - The community mobilization and social marketing program promoting a preventive
      approach of weekly iron-folic acid supplementation in women of reproductive age
      improved iron status of non-pregnant women in Vietnam. Three to six months of
      weekly pre-pregnancy supplementation and regular weekly intake of supplements
      during pregnancy allowed women to achieve good iron and hemoglobin status during
      the two first trimesters of pregnancy. In the third trimester, iron deficiency
      and anemia were notably present but low birth weight prevalence was low. This
      demonstrates the effectiveness and safety of the preventive approach as
      implemented here to prevent and control iron deficiency and anemia in women of
      reproductive age before and during pregnancy.

PMID- 16466086
TI  - Weekly iron-folic acid supplementation to improve iron status and prevent
      pregnancy anemia in Filipino women of reproductive age: the Philippine experience
      through government and private partnership.
AB  - With the participation of the government and private sectors in the Philippines,
      weekly iron-folic acid supplementation introduced within a social marketing
      framework and a social mobilization campaign successfully improved knowledge and
      practice of buying and regularly taking supplements by women of reproductive age,
      both pregnant and non-pregnant. Adolescent girls in school were also active
      participants.

PMID- 16466087
TI  - Government-industry partnership in weekly iron-folic acid supplementation for
      women of reproductive age in the Philippines: impact on iron status.
AB  - The effectiveness of weekly iron-folic acid supplements promoted through a
      government-industry partnership was assessed in pregnant and non-pregnant women
      in the Philippines. Compliance to both weekly and daily supplementation increased
      during the year-long study period, but was highest with weekly supplementation.
      Serum ferritin and hematocrit increased significantly, whereas the hemoglobin
      level showed minimal change, probably because of lack of other heme-forming
      nutrients such as vitamin A. Serum ferritin increments were significantly higher
      in women taking the iron-folic acid supplements for more than 6 weeks. Weekly
      iron-folic acid supplementation should be recommended as a preventive strategy to
      control iron deficiency among reproductive-age women in the Philippines.

PMID- 16466088
TI  - Weekly iron-folic acid supplements to prevent anemia among Cambodian women in
      three settings: process and outcomes of social marketing and community
      mobilization.
AB  - Social marketing and community mobilization approaches were applied in a pilot
      program to introduce weekly iron-folic acid supplementation to prevent anemia in
      Cambodian women of reproductive age. The program was implemented in three very
      different environments: secondary school girls, women working in garment
      factories in the vicinity of Phnom Penh, and women in rural villages. Each
      population provided its own challenges and obstacles. However, all three groups
      of women showed substantial improvements in knowledge about the causes,
      consequences, and prevention of anemia, and the large majority reported interest
      in continuing to take the supplements.

PMID- 16466089
TI  - Positive impact of a weekly iron-folic acid supplement delivered with social
      marketing to Cambodian women: compliance, participation, and hemoglobin levels
      increase with higher socioeconomic status.
AB  - A social marketing program promoting weekly iron-folic acid supplementation
      improved hemoglobin levels in women of reproductive age in Cambodia.
      Supplementation was increasingly effective among women of higher socioeconomic
      status (SES). Among higher SES schoolgirls, 58% took the supplements, compared
      with 49% for lower SES (P = 0.07). Garment factory workers with an 11th- or 12th
      grade education had a mean improvement in hemoglobin of 0.72 g/dL over those with
      a 5th-grade education or less (P = 0.04). The percentage of rural village women
      taking supplements increased with increasing SES (linear trend P = 0.046). These
      results suggest that women with lower SES be given special attention for future
      programs.

PMID- 16466090
TI  - Weekly iron and folic acid supplementation as a tool to reduce anemia among
      primary school children in Cambodia.
AB  - The prevalence of anemia decreased from 62% to 12% and from 57% to 26% in
      children 5 to 11 years of age in two rural primary schools in Kampot Province,
      Cambodia, after oral weekly supplementation with iron-folic acid tablets for 20
      weeks and with vitamin A and mebendazole twice per year. In 12- to 15-year-old
      children, success was less marked. The prevalence of hookworm infestation did not
      change, but the number of eggs in the stool decreased drastically. The
      intervention had no significant influence on stunting and wasting. An integrated
      community approach including mass deworming, health education, and multi
      micronutrient supplementation was very effective in reducing anemia in Cambodian
      schoolchildren and should be adopted on a larger scale.

PMID- 16466091
TI  - Industry experience in promoting weekly iron-folic acid supplementation in the
      Philippines.
AB  - After participating in a pilot project under a government-industry partnership to
      promote the adoption of weekly iron-folic acid supplementation among women of
      reproductive age in the Philippines in 1998, United Laboratories (UNILAB), the
      Philippines' largest private pharmaceutical company, decided in April 2002 to
      launch a weekly iron-folic acid supplement for pregnant and non-pregnant women
      under the brand name Femina. The business objective set for the Femina brand was
      to build the category of preventive iron-folic acid supplements in line with the
      Philippine Department of Health's advocacy on weekly supplementation as an
      alternate to daily dosing to reduce the prevalence of anemia in the country. The
      brand was supported with an integrated mix of traditional advertising media with
      complementary direct-to-consumer educational programs that aimed to create
      awareness of iron-deficiency anemia, its causes and effects, and the role of
      weekly intake of iron-folic acid in preventing the condition. Aggressive
      marketing support for 1 year was successful in creating awareness among the
      target women. Significant lessons derived from consumers identified opportunity
      areas that can be further addressed in developing advocacy programs on weekly
      iron supplementation implemented on a nationwide scale in the future.

PMID- 16466092
TI  - Weekly iron-folic acid supplementation of women of reproductive age: impact
      overview, lessons learned, expansion plans, and contributions toward achievement
      of the millennium development goals.

PMID- 16466093
TI  - Recurrent respiratory papillomatosis.
AB  - Recurrent respiratory papillomatosis is a frustrating and challenging disease for
      surgeons, patients, and patients' families. Although the voice and airway
      manifestations are managed surgically, a "cure" for this disease remains elusive.
      In this edition of the "Seminar Series," we endeavor to review the current
      literature regarding the epidemiology, etiology, clinical manifestations, and
      surgical and medical treatments of this disorder. The key to future management of
      recurrent respiratory papillomatosis may lie in its prevention, if current
      efforts to develop an effective vaccine come to fruition.

PMID- 16466094
TI  - Can Ki-67 predict recurrence of NO squamous cell carcinoma of the tongue?
AB  - OBJECTIVES: Ki-67 is a molecular marker of cellular proliferation that predicts
      prognosis of some head and neck tumors. Studies of Ki-67 in oropharyngeal cancer
      have yielded conflicting findings. This study was designed to test Ki-67 as a
      marker for poor prognosis in N0 tongue squamous cell carcinoma. METHODS: We
      examined 29 cases in a retrospective cohort to test the hypothesis that a high
      rate of tumor cell proliferation (high levels of Ki-67 staining) at the invasive
      edge of N0 squamous cell carcinoma of the tongue correlates with increased risk
      of recurrence. RESULTS: There were 14 cases of recurrence. The average age of the
      patients with recurrence was 58 years. The average time to recurrence was 13.1
      months. A 0% to 33% uptake of Ki-67 at the tumor's leading edge was associated
      with a 6-times-greater risk of recurrence. The mean length of survival for the
      group with 0% to 33% uptake was 21 months; for the group with > 33% uptake, it
      was 33 months. Overall uptake of Ki-67 and histologic grade did not correlate
      with risk of recurrence. CONCLUSIONS: In this sample, low rates of Ki-67 staining
      at the invasive edge of the tumor predicted a risk of recurrence. These results
      need to be confirmed before Ki-67 can be used for predicting recurrence of tongue
      squamous cell carcinoma.

PMID- 16466095
TI  - Tongue paresthesia and dysgeusia following operative microlaryngoscopy.
AB  - OBJECTIVES: This study was performed to assess the overall incidence and duration
      of alterations in tongue sensation and taste after operative microlaryngoscopy,
      and the relation of these symptoms to operative time. METHODS: We performed a
      retrospective review of information regarding tongue symptoms in patients who
      completed standard post-microlaryngoscopy follow-up at 1 week, 1 month, and 3
      months. RESULTS: One hundred patients (54 male and 46 female; mean age, 46 years;
      age range, 14 to 83 years) met the inclusion criteria. Eighteen patients had
      positive findings at 1 week: 15 complained of paresthesia and 3 of dysgeusia. The
      symptoms decreased over time without treatment (4% of patients at 1 month and 1%
      of patients at 3 months). Only 1 case of dysgeusia persisted past 3 months.
      Gender was found to be a significant independent risk factor for the development
      of symptoms (odds ratio, 5.63; 95% confidence interval, 1.36 to 31.29; p = .013).
      Patients whose operations lasted longer than 1 hour were almost 4 times more
      likely to develop tongue-related symptoms than those with an operative time less
      than 30 minutes, although these findings did not achieve statistical significance
      (odds ratio, 3.91; 95% confidence interval, 0.62 to 30.95; p = .182).
      CONCLUSIONS: Alterations in tongue sensation and taste, most likely due to
      lingual nerve injury, are common after microlaryngoscopy, especially in female
      patients. They also tend to be associated with longer operative times. Although
      transient in nearly every case, lingual paresthesia and dysgeusia should form
      part of the preoperative discussion with the patient.

PMID- 16466096
TI  - Morphological and histologic examination of the epiglottis: implications for
      improving epiglottic closure technique.
AB  - OBJECTIVES: We conducted a histologic examination and measured the tension on the
      epiglottis to determine how dehiscence of the epiglottis can be prevented after
      epiglottic closure surgery. METHODS: We classified configurations of the
      epiglottis into flat, intermediate, and omega types and studied the histology of
      each type. We also measured the tension in each of these 3 morphological types on
      4 regions of the epiglottis (upper, middle, and lower points, and the cuneiform
      tubercle) at 3 different times: before incision, after median incision, and after
      reversed-Y incision. RESULTS: No histologic differences were evident among the
      epiglottic types. In the flat and intermediate types, the tension measured before
      incision decreased significantly upon completion of the median incision at every
      point. In these 2 types, the reversed-Y incision resulted in a further
      significant decrease in tension at the middle and lower points. In the omega
      type, the tension was low before incision and was not significantly reduced by
      either incision. CONCLUSIONS: We demonstrated that a median incision alone
      effectively decreased tension sufficiently to prevent dehiscence. The reversed-Y
      incision was even more effective for decreasing tension at the middle and lower
      points.

PMID- 16466097
TI  - Endoscopic treatment of severe tracheal stenosis.
AB  - OBJECTIVES: Endoscopic treatment of subglottic and tracheal stenosis has
      traditionally been reserved for short-segment and web-like stenoses with normal
      cartilage. This retrospective case series review was undertaken to examine my
      experience with definitive endoscopic treatment for circumferential and complete
      tracheal stenosis with loss of cartilaginous support. METHODS: Patients who
      presented with tracheostomy dependence or dyspnea as a result of clinically
      significant tracheal stenosis over a 2-year period were treated endoscopically.
      Mitomycin C was applied after dilation in 19 patients. Three patients with
      complete stenosis and cartilage collapse underwent endoscopic placement of a
      silicone elastic stent, which was in place for less than 23 days. RESULTS: Twenty
      patients were treated for tracheal stenosis over a 2-year period. No surgical
      complications were observed after operation in the endoscopic treatment group.
      Three of 6 patients with complete stenoses and 8 of 10 patients with
      circumferential stenoses with cartilage involvement gained airways that remained
      patent. Nine patients' stenoses resolved after the initial treatment. Three
      patients (15%) eventually required tracheal resection. The follow-up periods
      ranged from 5 to 25 months. CONCLUSIONS: Although some limitations apply, severe
      and complete tracheal stenoses may be successfully treated endoscopically with
      the techniques described. Definitive endoscopic treatment may be considered
      before tracheal resection in select cases. Endoscopic treatment is associated
      with few complications, low morbidity, a short operative time, and a short length
      of hospitalization.

PMID- 16466098
TI  - Deltopectoral flap revisited in the microvascular era: a single-institution 10
      year experience.
AB  - OBJECTIVES: In 1965, Bakamjian described the deltopectoral (DP) flap as a
      reconstructive option in head and neck surgery. It served as the premier flap for
      reconstructing complex head and neck defects until the late 1970s. Today, the DP
      flap is often overlooked; although its role has diminished, its use is still
      warranted in certain select clinical situations. METHODS: A retrospective patient
      chart review of 25 DP flap procedures performed at the University of Iowa
      Hospitals and Clinics and Iowa City Veterans Administration Hospital between
      January 1, 1991, and June 1, 2002, was undertaken. The data collected included
      patient demographics and assessment of DP flap survival and its ability to
      accomplish established preoperative reconstructive goals. RESULTS: The DP flap
      was used for the following situations: vascularized skin coverage of the neck,
      carotid arteries, and face (16 cases), including simultaneous coverage of other
      reconstructive flaps in 6 cases; controlled orocutaneous fistula development (3
      cases) or fistula closure (5 cases); and pharyngoesophageal reconstruction (4
      cases). In 3 cases the flap was used for more than one of the preoperative goals
      described above (n = 25). Minor flap-related complications that required local
      wound treatment developed in 5 cases (20.0%), but the flaps were successfully
      salvaged and no subsequent reconstructive procedure was required. In an
      additional 5 cases (20.0%), the flap failed in some measure to accomplish its
      preoperative goal, necessitating further surgical reconstruction. Sixteen
      patients (64%) had undergone previous or simultaneous reconstructive procedures
      that limited other available reconstructive options. CONCLUSIONS: The technical
      simplicity of the DP flap, coupled with its predictable vascular supply, has
      allowed it to maintain a niche role in contemporary reconstructive surgery. The
      DP flap provides an excellent method of reconstruction in select cases in which
      vascularized skin coverage of the neck is needed. The DP flap also provides a
      valuable salvage option in situations in which other reconstructive techniques
      are not possible.

PMID- 16466099
TI  - Preoperative predictive factors for hearing preservation in vestibular schwannoma
      surgery.
AB  - OBJECTIVES: We performed a retrospective chart review to evaluate the various
      predictive factors for postoperative hearing preservation in the surgical
      management of vestibular schwannoma. METHODS: Of 792 patients operated on for
      vestibular schwannoma between April 1987 and July 2002, 107 were candidates for
      hearing preservation surgery. These patients were divided into group 1 (hearing
      preserved) and group 2 (hearing not preserved), and both of these groups were
      evaluated for age, sex, pure tone average, sound discrimination score, tumor
      size, and auditory brain stem response parameters. A corrected chi2 test and a
      corrected t-test were used for statistical analysis. Multiple regression analysis
      was further done to evaluate independent predictive factors, either alone or in
      combination. The results were evaluated by use of the modified Sanna
      classification and the guidelines of the American Academy of Otolaryngology-Head
      and Neck Surgery (AAO-HNS). RESULTS: Preoperative pure tone average and tumor
      size were the 2 predictive factors in our study. A Pearson correlation test
      showed that there was no multicollinearity between the factors. On multiple
      regression analysis by backward elimination of nonsignificant factors, we found
      that tumor size is an independent predictive factor for postoperative hearing.
      According to the modified Sanna classification, postoperative hearing was
      preserved in 11.2% of patients (equivalent to class A of AAO-HNS guidelines).
      CONCLUSIONS: In our series, preoperative pure tone average and tumor size were
      found to be predictors of postoperative hearing levels.

PMID- 16466100
TI  - Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response:
      role in laryngopharyngeal reflux disease.
AB  - OBJECTIVES: The objectives of this study were to define the conditions that give
      rise to a stress protein response in laryngeal epithelium and to investigate
      whether and how stress protein dysfunction contributes to reflux-related
      laryngeal disease. METHODS: Western analysis was used to measure stress protein
      (squamous epithelial proteins Sep70 and Sep53 and heat shock protein Hsp70) and
      pepsin levels in esophageal and laryngeal tissue specimens taken from both normal
      control subjects and patients with pH-documented laryngopharyngeal reflux (LPR)
      who had documented lesions, some of whom had laryngeal cancer. A porcine organ
      culture model was used to examine the effects of low pH and pepsin (0.1% porcine
      pepsin A) on stress protein levels. A laryngeal squamous carcinoma (FaDu) cell
      line was used to examine uptake of human pepsin 3b-tetramethyl-5 and -6
      isothiocyanate. RESULTS: Sep70, Sep53, and Hsp70 were found to be expressed at
      high levels, and pepsin was not detected, in esophageal and laryngeal specimens
      taken from normal control subjects and in esophageal specimens taken from LPR
      patients. The patients with LPR were found to have significantly less laryngeal
      Sep70 (p = .027) and marginally less laryngeal Sep53 (p = .056) than the normal
      control subjects. Laryngeal Hsp70 was expressed at high levels in the LPR
      patients. The patients with laryngeal cancer had significantly lower levels of
      Sep70, Sep53 (p < .01), and Hsp70 (p < .05) than the normal control subjects. A
      significant association was found between the presence of pepsin in laryngeal
      epithelium from LPR patients and depletion of laryngeal Sep70 (p < .001). Using
      the organ culture model, we demonstrated that laryngeal Sep70 and Sep53 proteins
      are induced after exposure to low pH. However, in the presence of pepsin, Sep70
      and Sep53 levels are depleted. Confocal microscopy analysis of cultured cells
      exposed to labeled pepsin revealed that uptake is by receptor-mediated
      endocytosis. CONCLUSIONS: These findings suggest that receptor-mediated uptake of
      pepsin by laryngeal epithelial cells, as may occur in LPR, causes a change in the
      normal acid-mediated stress protein response. This altered stress protein
      response may lead to cellular injury and thus play a role in the development of
      disease.

PMID- 16466101
TI  - Immunohistochemical distinction of intestinal-type sinonasal adenocarcinoma from
      metastatic adenocarcinoma of intestinal origin.
AB  - OBJECTIVES: Distinction of intestinal-type sinonasal adenocarcinoma (ITAC) from
      adenocarcinoma of intestinal origin metastatic to the sinonasal cavity may be
      extremely difficult on histologic grounds alone. We studied the role of
      cytokeratin (CK) and mucin (MUC) expression in differentiating ITAC, metastatic
      adenocarcinoma of intestinal origin, and non-intestinal-type sinonasal
      adenocarcinoma (non-ITAC). METHODS: We stained specimens from 5 cases of ITAC and
      4 cases of non-ITAC, along with 4 colonic and 3 duodenal adenocarcinoma controls,
      with CK7 and CK20, MUC2 and MUC5, neuron-specific enolase (NSE), chromogranin
      (CHR), and carcinoembryonic antigen (CEA) in order to examine the possible
      combinations of markers that best aid in the diagnosis of these lesions. We also
      performed a retrospective review of our clinical experience with these rare
      lesions. RESULTS: CK7 staining was positive in all ITAC and non-ITAC cases,
      whereas all cases displaying gastrointestinal-type differentiation (ITAC and
      metastatic intestinal cases) stained positive for both CK20 and MUC2. Staining
      for MUC5, NSE, CHR, and CEA was variable. CONCLUSIONS: Tumors with the CK7+,
      CK20+, MUC2+ immunophenotype are likely primary sinonasal lesions, whereas tumors
      with the CK7-, CK20+, MUC2+ profile warrant further clinical evaluation to
      exclude metastatic disease from the gastrointestinal tract. Complete surgical
      resection of ITAC remains the mainstay of therapy.

PMID- 16466102
TI  - Human nasal polyp microenvironment maintained in viable and functional states as
      xenografts in SCID mice.
AB  - OBJECTIVES: We undertook to maintain human nasal polyp tissue in a viable and
      functional state in SCID (severe combined immunodeficiency) mice. METHODS: Small,
      nondisrupted pieces of human nasal polyp tissues were subcutaneously implanted
      into SCID mice depleted of natural killer cells. The resulting xenografts were
      examined histologically, and the sera were evaluated for the presence of human
      protein. RESULTS: The original histologic architecture of the polyp was
      maintained in the xenografts. The tissues, including pseudostratified columnar
      epithelial-lined polyps and subepithelial stroma, remained viable, and goblet
      cells continued to produce mucin for up to 26 weeks after engraftment. Human
      inflammatory leukocytes, including CD3+ T cells, CD20+ B cells, CD138+ plasma
      cells, and CD68+ monocytes and/or macrophages, were present. Identification of
      human immunoglobulin and human interferon-gamma in the sera of xenograft-bearing
      mice indicated that the B cells or plasma cells and T cells within the xenografts
      remained functional for 2 weeks after engraftment. CONCLUSIONS: The ability to
      engraft and maintain nasal polyps provides an in vivo human/mouse chimeric model
      with which to investigate the role of inflammatory leukocytes and stromal cells
      in the maintenance and progression of polyposis and to determine how exogenous
      cytokines may alter the interaction of inflammatory cells, stromal cells, and
      epithelial cells in the polyp.

PMID- 16466103
TI  - Pulsed immunosuppression with everolimus and anti-alphabeta T-cell receptor:
      laryngeal allograft preservation at six months.
AB  - OBJECTIVES: Laryngeal transplantation can restore the voice in patients who have
      undergone laryngectomy. However, the prospect of lifelong immunosuppression is a
      drawback to this procedure. We present data from a study aimed at minimizing the
      need for immunosuppression while maintaining graft viability through a novel
      pulsed-dosing protocol. METHODS: Larynges were transplanted from Lewis-brown
      Norway (RT1(l+n, F1) rats to Lewis (RT1(l)) recipients. All recipients received 7
      days of treatment with everolimus and mouse anti-rat alphabeta T-cell receptor
      (anti-TCR) monoclonal antibodies beginning the day before transplantation. At 90
      days after transplantation, all recipients received a pulse of the same treatment
      combination for 5 days. From 90 to 180 days after transplantation, the rats
      received no treatment (group 1, n = 5), 2.5 mg/kg everolimus per day (group 2, n
      = 5), or 1.0 mg/kg everolimus per day (group 3, n = 5). RESULTS: Histologic
      analysis of rats that received everolimus as pulse therapy evidenced no signs of
      rejection, whereas animals that were untreated after 90 days had normal to mild
      chronic rejection. T-cell reconstitution occurred 65 days after perioperative
      immunosuppressive treatment, but less rapidly after pulse therapy. Also,
      peripheral chimerism was generated in all 3 groups. CONCLUSIONS: In the rat
      laryngeal transplantation model, short-term perioperative therapy with everolimus
      and anti-TCR followed by pulsing is a viable alternative to the concerns
      associated with continuous, lifelong immunosuppression.

PMID- 16466104
TI  - Transforming growth factor beta expression during an inner ear immune response.
AB  - OBJECTIVES: The involvement of transforming growth factor beta (TGF-beta), a
      strong mediator of fibrogenesis, during cochlear immune responses was
      investigated. METHODS: An inner ear adaptive immune response to antigen was
      created in mice that were painlessly sacrificed 3 to 48 hours and 7 days after
      initiation of the immune response. The cochleas were assayed by
      immunocytochemistry for TGF-beta and latency-associated peptide (LAP). RESULTS:
      We found LAP expressed in normal cochleas and the endolymphatic sac, in the small
      round cells in the cochlear scalae and the mesothelial cells under the basilar
      membrane, and in the endolymphatic sac perisaccular area. We found TGF-beta
      expressed in infiltrated, inflammatory cells in the scalae and the endolymphatic
      sac lumen 3 hours after cochlear antigen challenge. At this time, LAP
      immunoreactivity was decreased. This rapid shift in immunoreactivity provides
      evidence for activation of TGF-beta during an immune response. This reversal of
      expression persisted for 48 hours, but conditions reverted to normal after 7
      days. Surgical controls did not show TGF-beta expression. CONCLUSIONS: We
      conclude that TGF-beta activation occurs in the early phase of a cochlear
      adaptive immune response and is down-regulated as the response resolves. This
      finding suggests that the process of cochlear fibrosis starts early and that
      proper treatment could prevent cochlear fibrosis.

PMID- 16466105
TI  - The "tako-tsubo" phenomenon and myocardial infarction.

PMID- 16466106
TI  - Cardiac tamponade: still being newly described.

PMID- 16466107
TI  - Patent foramen ovale.

PMID- 16466108
TI  - Hydralazine-induced lupus.

PMID- 16466109
TI  - The role of inflammation in diabetes and its complications.

PMID- 16466110
TI  - Fluctuating blood glucose levels in an elderly diabetic patient.

PMID- 16466111
TI  - What we know about ourselves: changing attitudes about treating patients with
      substance use disorders.

PMID- 16466112
TI  - Pathological gambling.

PMID- 16466113
TI  - Antisperm antibodies and varicocele.

PMID- 16466114
TI  - Is ilioinguinal-iliohypogastric nerve block an underused anesthetic technique for
      inguinal herniorrhaphy?

PMID- 16466115
TI  - Drug-induced QT prolongation.

PMID- 16466116
TI  - Hiding in plain sight: a new paradigm for "opportunistic infections".

PMID- 16466117
TI  - Hydralazine-induced lupus: maintaining vigilance with increased use in patients
      with heart failure.
AB  - OBJECTIVE: To review data concerning the incidence and danger of hydralazine
      induced systemic lupus erythematosus (SLE) and review how best to monitor
      patients placed on chronic hydralazine therapy. DATA SOURCES: Literature was
      sought utilizing PUBMED (1960 to present) and MEDLINE (1966 to present). Search
      terms included hydralazine, drug-induced systemic lupus erythematosus, congestive
      heart failure, and antinuclear antibody. DATA SYNTHESIS: A major adverse effect
      of hydralazine therapy is drug-induced SLE. An evaluation of case reports and
      review of the literature was undertaken to determine the significance of this
      major adverse effect and stress the importance of close monitoring of patients
      placed on chronic hydralazine therapy for heart failure. Risk factors are
      discussed including high daily doses, slow acetylator and HLA-DRw4 phenotypes,
      therapy longer than 3 months, and female gender. CONCLUSIONS: Following the
      publication of A-HeFT, an increase in the amount of hydralazine prescribed in
      patients with heart failure has been noted. Patients should be closely monitored
      when initiating hydralazine and during chronic therapy. Although dose limitation
      of hydralazine reduces risk, low doses are well documented to be associated with
      SLE. A baseline antinuclear antibody level should be determined on initiation of
      hydralazine, but it is not recommended to regularly check antinuclear antibody
      levels because a positive result does not necessarily indicate SLE is present.
      Patients should be monitored at each visit for signs and symptoms of SLE, and, if
      any signs and symptoms of the syndrome develop while the patient is on
      hydralazine therapy, the drug should be discontinued immediately because
      complications from the syndrome can be potentially fatal.

PMID- 16466118
TI  - Correlation of high-sensitivity C-reactive protein and plasma fibrinogen with
      individual complications in patients with type 2 diabetes.
AB  - OBJECTIVE: We investigated the correlation between acute-phase reactants, ie,
      high-sensitivity C-reactive protein (hsCRP) or fibrinogen and diabetic
      complications. METHODS: In 73 patients with type 2 diabetes, we investigated
      associations between both markers and carotid artery intimal medial complex
      thickness (IMT), heart rate variability, or urinary albumin excretion (UAE).
      RESULTS: Log hsCRP and fibrinogen correlated significantly with each other (r =
      0.3701, P = 0.0013). Fibrinogen correlated negatively with the coefficient of
      variation of RR intervals (CV(RR)) and positively with log UAE (r = -0.2433, P =
      0.0381; r = 0.4815, P < 0.0001), while log hsCRP did not. Furthermore both log
      hsCRP and fibrinogen did not correlate with IMT. CONCLUSION: We concluded that
      despite their close correlation, fibrinogen compared with hsCRP might be closely
      associated with diabetic microangiopathy and that both markers might not
      correlate with IMT as a marker of macroangiopathy.

PMID- 16466119
TI  - Physicians-in-training attitudes toward caring for and working with patients with
      alcohol and drug abuse diagnoses.
AB  - INTRODUCTION: Physicians in all specialties commonly encounter patients who abuse
      alcohol or illegal drugs. Working with these patient populations can be
      challenging and potentially engender negative attitudes. This study is designed
      to identify the progression of attitudinal shifts over time of physicians-in
      training toward caring for substance abusing patients. METHODS AND MATERIALS: A
      31-item survey was designed to capture demographic information of participants,
      attitudes toward treating patients with substance abuse diagnoses, previous
      participant education, experience in and comfort with diagnosing and treating
      substance abuse, and satisfaction achieved in working with this patient
      population. Medical students in their third and fourth years of education as well
      as residents in training, years one through four, were surveyed. Responses to the
      survey's attitudinal items were analyzed across years of training, looking for
      changes associated with time and experience. RESULTS: Fifty-seven percent of
      eligible participants anonymously completed the survey. There was general
      agreement across all years of training that health care professionals should be
      allowed continued employment in their professions when in recovery from alcohol
      abuse (P = 0.424) and drug abuse (P = 0.409). Across years of training there was
      agreement that patients can recuperate and provide meaningful contributions to
      society when recovering from alcohol (P = 0.847) and drug (P = 0.859) abuse. From
      medical school years through residency there were enhanced beliefs that alcohol
      abusing patients (P = 0.027) and drug-abusing patients (P = 0.009) overutilize
      health care resources. Most trainees, despite year of education, believe patients
      who abuse alcohol (P = 0.521 and illegal drugs (P = 0.356) have challenging
      medical and social issues from which they can learn. There was consistency across
      years in the perception that providing care to alcohol-abusing patients (P =
      0.679) and drug-abusing patients (P = 0.090) is repetitive and detracts from the
      care of others. All felt their training was adequate to care for alcohol (P =
      0.628) and drug-abusing patients (P = 0.484). Satisfaction achieved in caring for
      alcohol (P = 0.017) and illegal drug-abusing patients (P = 0.015) consistently
      diminishes over years in training. CONCLUSIONS: There are positive as well as
      negative aspects for physicians-in-training to caring for patients with alcohol
      and illegal drug abuse problems. Combining effective education strategies with
      the needs of physicians at specific points in their education may be effective in
      reversing the negative trends seen in attitudes toward caring for patients with
      substance abuse problems.

PMID- 16466120
TI  - Neuropsychological performance, impulsivity, and comorbid psychiatric illness in
      patients with pathological gambling undergoing treatment at the CORE Inpatient
      Treatment Center.
AB  - INTRODUCTION: Pathologic gambling is a disorder with features that implicate
      abnormal functioning in brain regions involved in addiction, mood, anxiety, and
      impulse control disorders. Our goal was to examine brain function with
      neurocognitive tasks that target these brain regions in patients with pathologic
      gambling. METHODS: Patients were evaluated for comorbid psychiatric disorders,
      impulsivity, and performance on reversal-learning and reward-based decision
      making cognitive tasks. RESULTS: Patients had higher impulsivity scores and
      significant deficits on both cognitive tasks compared with controls. All subjects
      also had comorbid psychiatric disorders, including mood, anxiety, psychotic, and
      substance abuse. CONCLUSION: The cognitive deficits and impulsivity are
      consistent with abnormal activity in orbitofrontal-limbic networks. The high
      level of comorbidity is consistent with the overall severity in these inpatients
      undergoing treatment, and adds weight to the concept of a fundamental abnormality
      in this network.

PMID- 16466121
TI  - Varicocele and antisperm antibody: fact or fiction?
AB  - OBJECTIVE: To study the level of antisperm antibodies (ASAB) in the serum and
      semen of infertile men with varicocele before and 6 months after varicocelectomy.
      MATERIALS AND METHODS: We performed a prospective study of 81 infertile men
      undergoing microsurgical inguinal varicocelectomy. Female factor was excluded.
      Semen analysis and seminal and serum ASAB (direct and indirect IgG and IgA), as
      measured by SpermMar test, were performed before and after surgery at 6 months. A
      control group consisting of idiopathic infertile patients was evaluated for ASAB.
      RESULTS: Eighty-one patients with a mean age of 28.7 years (23 to 42) completed
      our study. Mean sperm count, motility, and abnormal forms were improved after
      surgery and were statistically significant for sperm density and morphology (P <
      0.05). Before surgery, 21 patients (26%) had a low positivity for ASAB (10 to
      40%). Six months after surgery, the ASAB titer was reduced in 15 (A group),
      increased in 3 (B group), and reduced in another 3 (C group). The C group also
      had an increase in other titers. In the A group sperm count, motility and normal
      forms improved after surgery (P < 0.05). In the B group, motility was reduced
      after surgery. In the C group, motility and normal forms were reduced after
      surgery. Sixty patients were negative for ASAB before surgery. Of these, 48
      showed an increase in at least one of the ASAB types to some degree that had no
      significant effect on semen parameters. In the control group, two patients (7%)
      were weakly positive for ASAB. CONCLUSIONS: Varicocelectomy may reduce the ASAB
      level, and this reduction has a good effect on semen parameter quality. Also, it
      may raise the ASAB level in some patients. This positive conversion has no
      adverse effect on semen parameters.

PMID- 16466122
TI  - Comparison of ilioinguinal-iliohypogastric nerve block versus spinal anesthesia
      for inguinal herniorrhaphy.
AB  - OBJECTIVE: This study was carried out to determine the optimal anesthetic
      technique for use in elective herniorrhaphy. METHODS: We retrospectively analyzed
      126 inguinal hernia repairs. The patients were allocated to one of two groups: an
      ilioinguinal-iliohypogastric nerve block group (IHNB group, n = 63) and spinal
      anesthesia group (SA group, n = 63). We recorded information about perioperative
      and postoperative parameters. RESULTS: There were statistically significant
      decreases in both mean arterial pressure and pulse rate in the SA group (P <
      0.001). None of the patients in the IHNB group required recovery room care.
      Patients in the IHNB group initiated oral intake (0.31 +/- 0.1 h) more quickly
      than patients in the SA group (5.74 +/- 0.1 h) (P < 0.001). The time-to-home
      readiness was significantly lower (14.1 +/- 1.5h) in group IHNB, compared with
      group SA (42.8 +/- 5.3h) (P < 0.001). First rescue analgesic time postoperatively
      was 3.30 +/- 0.2 hours in group SA and 2.7 +/- 0.13 hours in group IHNB (P <
      0.05). CONCLUSION: The use of IHNB for patients undergoing herniorrhaphy resulted
      in a shorter time-to-home readiness, quicker oral intake post surgery, and no
      need for recovery room care, when compared with the use of SA.

PMID- 16466123
TI  - Effect of ciprofloxacin and levofloxacin on the QT interval: is this a
      significant "clinical" event?
AB  - BACKGROUND: The widespread use of the fluoroquinolones has raised the question of
      the cardiac safety of these medications. This widespread use of this class of
      antibiotics has displayed their safety profile, which is actually more favorable
      than many other drug classes. The cardiac toxicity issue at the center of this
      discussion is the prolongation of the QT interval leading to torsade de pointes.
      Ciprofloxacin and levofloxacin, two of the more commonly used fluoroquinolones,
      are considered less likely than other fluoroquinolones to prolong the QT
      interval. The authors set out to evaluate the effect on the QT interval of
      patients after administration of ciprofloxacin and levofloxacin. METHODS: A
      prospective evaluation of 38 consecutive patients evaluated by the infectious
      disease service and receiving either ciprofloxacin or levofloxacin was
      undertaken. Twelve-lead electrocardiograms were obtained at baseline and at least
      48 hours after the first dose of the antibiotic was administered. Both the
      longest QT interval and the mean QT interval were evaluated. To account for
      variations in heart rate, the corrected QT interval was calculated by using
      Bazett's formula (QTc = QT(square root of) R-R). Statistical analysis was
      undertaken to assess for the presence of a change after the administration of the
      antibiotic. RESULTS: Thirty-eight patients (mean age, 65 +/- 19 years), 23 women
      and 15 men, were studied. There was a small but significant increase in the
      longest QTc intervals over baseline in patients receiving levofloxacin; there was
      no significant change in the mean QTc interval. However, one patient who received
      levofloxacin was, statistically, an outlier and, on retrospective analysis, had
      demonstrated severe electrolyte disturbances at the time of the study. When this
      patient was excluded, the increase in the longest QTc interval was not
      significant. Patients receiving ciprofloxacin did not demonstrate any significant
      change in the longest QTc interval or mean QTc interval. CONCLUSIONS: Neither
      levofloxacin nor ciprofloxacin significantly prolonged the mean QTc interval over
      baseline. When electrolyte deficiencies in one of the patients evaluated were
      taken into account, this also held true for the longest QTc interval. There is,
      therefore, evidence that taking ciprofloxacin or levofloxacin, assuming that
      there are not any concurrent risk factors, will not cause a significant
      prolongation in the QT interval.

PMID- 16466124
TI  - Inflammatory aspects of sleep apnea and their cardiovascular consequences.
AB  - Obstructive sleep apnea (OSA) is a common medical condition that occurs in a
      considerable percentage of the population. Substantial evidence shows that
      patients with OSA have an increased incidence of hypertension compared with
      individuals without OSA, and that OSA is a risk factor for the development of
      hypertension. It is established that OSA may be implicated in stroke and
      transient ischemic attacks. OSA is associated with coronary heart disease, heart
      failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with
      OSA, especially in patients with pre-existing pulmonary disease. Although the
      exact cause that links OSA with cardiovascular disease is unknown, there is
      evidence that OSA is associated with a group of proinflammatory and prothrombotic
      factors that have been identified as important in the development of
      atherosclerosis. OSA is associated with increased daytime and nocturnal
      sympathetic activity. Autonomic abnormalities seen in patients with OSA include
      increased resting heart rate, decreased R-R interval variability, and increased
      blood pressure variability. Both atherosclerosis and OSA are associated with
      endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen,
      plasminogen activator inhibitor, and reduced fibrinolytic activity. OSA has been
      associated with enhanced platelet activity and aggregation. Leukocyte adhesion
      and accumulation on endothelial cells are common in both OSA and atherosclerosis.
      Clinicians should be aware that OSA may be a risk factor for the development of
      cardiovascular disease.

PMID- 16466125
TI  - A rare case of tako-tsubo cardiomyopathy complicated by a left ventricular
      thrombus.
AB  - Tako-tsubo cardiomyopathy is a rare stress-related cardiomyopathy usually seen in
      postmenopausal women after an emotional stressor. Patients generally present with
      angina-like substernal chest pain. The electrocardiogram (ECG) shows ST segment
      elevation or T wave inversions across the anterior precordial leads. Cardiac
      markers are minimally elevated, without evidence of coronary artery disease on
      angiography. The ventriculogram demonstrates hypokinesis and ballooning of the
      apex with hyperkinesis of the base. Prognosis is favorable with normalization of
      wall motion abnormalities within weeks. We present a rare case tako-tsubo
      cardiomyopathy complicated by a left ventricular mural thrombus. It is thought
      that this thrombus may have been precipitated by the ventricular dyskinesis.
      Further research is needed to determine the true incidence of left ventricular
      thrombus and the role of short-term anticoagulant therapy in this disorder.

PMID- 16466126
TI  - Complete heart block and cardiac tamponade secondary to Merkel cell carcinoma
      cardiac metastases.
AB  - This is a unique case of Merkel cell carcinoma, a rare neuroendocrine tumor,
      metastasizing to the heart and inducing a progression of cardiac complications
      such as new-onset atrial fibrillation, malignant pericardial effusion with
      tamponade physiology, first-degree heart block, and complete heart block.
      Metastases to the heart are relatively rare but should be suspected if a patient
      with a known neoplasm presents with new cardiac manifestations. This is the first
      case report of cardiac metastases from Merkel cell carcinoma causing cardiac
      tamponade or complete heart block. This case highlights the clinical decision
      making involved in managing cardiac tamponade and complete heart block in the
      setting of metastatic disease to the heart.

PMID- 16466127
TI  - Refractory hypoxemia in right ventricular infarction: a case report.
AB  - Right ventricular infarction has many clinical features. Although hypoxemia is a
      common presenting symptom with multiple causes in the setting of myocardial
      infarction, the authors present a case resulting from an acute right-to-left
      shunt secondary to a previously dormant patent foramen ovale. A 74-year-old male
      presented to the hospital after feeling unwell for the previous 2 days. Initial
      evaluation revealed marked hypoxemia without respiratory distress.
      Electrocardiographic findings and cardiac seromarkers revealed a completed
      inferior myocardial infarction. The patient's hypoxemia was refractory to 100%
      oxygen, indicating a right-to-left shunt. A transesophageal echocardiogram
      confirmed clinical suspicions for a right-to-left shunt through a patent foramen
      ovale. Despite sporadic reports in the literature, this still is a poorly
      recognized clinical condition. The authors review a case report that will enable
      the general intemist to consider a right-to-left shunt in the setting of
      hypoxemia in myocardial infarction.

PMID- 16466128
TI  - Acute pericarditis and renal failure complicating acute hepatitis A infection.
AB  - Hepatitis A infection may result in acute hepatitis, and rarely, fulminant
      hepatitis may ensue. Extrahepatic manifestations of hepatitis A are uncommon. The
      authors present the case of a 77-year-old male who had development of acute renal
      failure and pericarditis during the clinical course of acute hepatitis A
      infection. He died as a result of septic shock on the fifth day of
      hospitalization. To the best of our knowledge, this is the first report of both
      these rare and serious complications appearing in the same patient.

PMID- 16466129
TI  - Treatment of painful neuroma of amputated phalanx with distal toe transfer: a
      case report.
AB  - A painful neuroma in the amputation stump of a finger can be psychologically and
      physically disabling. Numerous surgical procedures have been attempted to prevent
      and treat amputation neuromas of the finger, but the results are inconsistent.
      Microsurgical transfer of the distal second toe to the amputated stump of the
      finger can provide a pathway and target for the regenerating axons and avoid
      recurrence of neuromas. In this article, we present the experience of successful
      treatment of amputation neuromas of an index finger with microsurgical distal toe
      transfer.

PMID- 16466130
TI  - Multiple adverse effects of pyridium: a case report.
AB  - Pyridium (phenazopyridine hydrochloride) is often prescribed as an analgesic in
      patients following trauma, surgery, or infections of the urinary tract. Pyridium
      toxicity has been previously reported, however, most cases result in a single
      adverse effect. Herein the authors describe an elderly patient who presented with
      simultaneous multiple adverse effects, including a previously undocumented
      myelosuppressive pancytopenia.

PMID- 16466131
TI  - Breast cancer metastasis to the gasserian ganglion.

PMID- 16466132
TI  - Hyperglycemia in an elderly diabetic patient: drug-drug or drug-disease
      interaction?

PMID- 16466133
TI  - Serum lipid profile in postmenopausal women with osteoporosis or osteopenia.

PMID- 16466134
TI  - Response to hypoglycemia--an enigmatic dilemma.

PMID- 16466135
TI  - Primary sternal osteomyelitis caused by Actinomyces israelii.

PMID- 16466136
TI  - Distribution of pleural effusion in congestive heart failure.

PMID- 16466137
TI  - Localized amyloidosis of cardiac and skeletal muscle: investigate promptly where
      it manifests.

PMID- 16466138
TI  - Pedometer-measured walking and risk factors for disease.

PMID- 16466139
TI  - The patient's page.

PMID- 16466140
TI  - [Responding to the demand].

PMID- 16466141
TI  - [EBM in pediatric surgery. Critical reading of articles. Treatment(I)].

PMID- 16466142
TI  - [Aplication of a 3D reconstruction model for the analysis of nitrofen induced
      intrathoracic malformations].
AB  - BACKGROUND: Three dimensional computer-assisted reconstruction offers some
      adventages for analysis and comparison of biological phenomena and anatomical
      structures. The CDH nitrofen-induced animal model associates multiple anomalies
      in neural-crest derived tissues. The goal of this study is to analyse by a 3-D
      reconstruction software the malformations in the extrinsic innervation of the
      esophagus in this model. METHODS: Nine control fetuses from 4 dams and 9 fetuses
      with CDH from 7 dams were studied. A thoracic block from the larynx to tracheal
      bifurcation was serially sectioned in the horizontal plane in every embryo. One
      in every 10 sections was stained with HE. The image was digitalized using
      biological software (TDR-3dbase). Vagus and recurrent laryngeal nerves, trachea,
      esophagus and the great vessels were examined. In order to obtain the 3-D
      reconstructions, 90 to 120 consecutive images were used. RESULTS: In comparison
      with controls there were striking abnormalities of these nerves in fetuses with
      CDH: 1) Absence of the left (2/9) or right (2/9) vagus nerves. 2) Absence of the
      left (3/9) or right (3/9) recurrent laryngeal nerves. 3) Marked hypoplasia of the
      trunk of the vagus (2/9). 4) Deviations of their normal course and change of
      normal anatomical relationships into the mediastinum (2/9). CONCLUSIONS: To
      fullfill our goals 3-D reconstructions allow a detailed analysis and provide a
      precise insight into the real anatomy. Rat fetuses with CDH have anomalies of the
      vagus and recurrent laryngeal nerves that support the concept of a neural crest
      involvement in the origin of this malformation. These observations may explain
      esophageal motility disorders in CDH.

PMID- 16466143
TI  - [Controversies in the therapeutical management of congenital diaphragmatic
      hernia: update by means of evidence-based medicine].
AB  - INTRODUCTION: Congenital diaphragmatic hernia (CDH) is one of the high-risk
      diseases in neonatal surgery. The aim of this article is to make an update of the
      controversies about the therapeutic management (time of surgery and modalities of
      medical stabilization) of CDH, by means of a systematic and critical review of
      the best scientific evidence in bibliography. METHODS: Systematic and structured
      review of the articles about therapeutic management of CDH (surgery, mechanical
      ventilation, inhaled nitric oxide, extracorporeal membrane oxygenation,
      surfactant, etc) published in secondary (TRIPdatabase, systematic review in
      Cochrane Collaboration, clinical practice guidelines, health technology
      assessment database, etc) and primary (bibliographic databases, biomedical
      journals, books, etc) publications and critical appraisal by means of methodology
      of the Evidence-Based Medicine Working Group. We selected the publications with
      the main scientific evidence in therapeutical articles (clinical trial,
      systematic review, meta-analysis and clinical practice guideline). RESULTS: The
      main secondary information is found in The Cochrane Library: 3 systematic review
      in the Neonatal Group (one specific about the time of surgery, and two related to
      the use of nitric oxide and extracorporeal membrane oxygenation in neonatal
      severe respiratory failure). But we found the main relevant articles in Pubmed
      database, mainly published in Journal Pediatric Surgery and with some clusters of
      investigation (Congenital Diaphragmatic Hernia Study Group in Texas University
      and Buffalo Institute of Fetal Therapy in New York University). CONCLUSIONS: From
      the evidence-based analysis, the results of CDH management between immediate
      versus delayed surgery were unclear, but delayed surgical (with pre-operative
      stabilization) has become preferred approach in many centers, and foetal surgery
      is not better than neonatal one. Opinion regarding the time of surgery has
      gradually shifted from early repair to a policy of stabilization and delayed
      repair. Because of associated persistent pulmonary hypertension and/or pulmonary
      hypoplasia in CDH, medical therapy is focused toward optimizing oxygenation while
      avoiding barotrauma, using gentle ventilation and permissive hypercarbia. High
      frequency oscillatory ventilation, inhaled nitric oxide and extracorporeal
      membrane oxygenation are used in severe cases, but these treatments do not
      clearly improve the outcome in neonates with CDH. The usefulness of surfactant
      and partial liquid ventilation are based in animal model experimentation, because
      the clinical trials in newborns are little and non-conclusive. Challenges for the
      future in this thematic area include the need for bigger and better trials of
      therapy in this field, with long-term outcomes among surviving children.

PMID- 16466144
TI  - [New surgical strategy in gastroschisis: treatment simplification according to
      its physiopathology].
AB  - INTRODUCTION: Gastroschisis (GS) is a congenital abdominal wall defect that
      permits bowel exposure to amniotic fluid (AF). Intestinal damage is related to
      the chemical action of AF and constriction. After birth at term, a thickened
      intestinal wall with inflammation and, in some cases, intestinal atresias were
      observed. Surgical repair and intestinal reubication may be difficult, and thus
      staged silo repair could be necessary. These patients require a long hospital
      stay owing to bowel damage causing severe intestinal hypoperistalsis and poor
      absorptive capacity. Total parenteral nutrition (TPN) is required for a long
      period. OBJECTIVE: The aim of this prospective study is to evaluate the benefits
      of a preterm delivery to avoid bowel damage and its post-natal consequences.
      PATIENTS AND METHODS: Six cases of prenatally-diagnosed GS have been treated
      following a new strategy since July 2002. A preterm Cesarean section (c-section)
      delivery was programmed at 34-35 weeks of gestational age (GA). Some hours after
      birth, at bedside in the NICU, bowel reduction through the defect hole was
      performed under general anesthesia. This preterm group (PT) was compared the past
      6 cases at term (AT) from January 1998 to July 2002. Macroscopic appearance,
      atresia existence, surgical technique, silo requirement, neonatal outcome, TPN
      and hospital stay were analyzed. RESULTS: All six cases AT (mean GA: 36.3 weeks)
      presented bowel inflammation and thickened wall. Only 2/6 cases allowed the
      intestine to be housed in a primary closure after laparotomy. 4/6 cases required
      staged silo repair. 1 patient presented intestinal atresia and other had
      perforations who died at 17 days of life from intestinal sepsis. Mean
      postoperative intubation period was 16.2 days. Mean TPN was 41.2 days and mean
      hospital stay 69.8 days. PT group was monitored by prenatal sonography seeking
      bowel sonolucency. After programmed PT c-section delivery (mean GA: 34.8 weeks)
      in all 6 cases, bowel loops presented normal appearance and intestinal thickening
      was absent, except in one case. No prematurity-related respiratory complications
      were observed. Easy bowel reduction without abdominal compression was performed
      in all cases. 1/6 cases required surgical release of occlusive intestinal
      adherence. Mean postoperative intubation period was 0.4 days (9.6 hours). Oral
      feeding was started at 6 days. Mean TPN was 13.4 days and mean hospital stay 28.6
      days. CONCLUSIONS: The third trimester is a critical period for fetal bowel
      development. Intestinal damage rises with increasing exposure time to amniotic
      fluid. This strategy of preterm delivery for the treatment of GS avoids
      intestinal damage, prevents "peel" and intestinal atresia, renders surgical
      reduction easier, reduces the hypoperistalsis, need for TPN and hospital stay.
      Multidisciplinary coordination between obstetricians, neonatologists and
      pediatric surgeons is required.

PMID- 16466145
TI  - [Liposuction in children: clinical utility].
AB  - Liposuction has become one of the most frequent aesthetic procedures. The
      "typical" patient is a young female with fat deposits in the trochanteric region.
      Gradually the safety of the technique together with the high satisfaction rate of
      the patients have contributed to the widening of its indications to other
      pathologies of the adipose tissue in different age populations. However, there is
      scarce literature regarding liposuction in childhood. The authors present their
      experience with liposuction as the treatment of congenital as well as acquired
      lipodystrophies in the paediatric age. Some particular details of the technique
      are described and the advantages of liposuction versus open surgery in these
      cases are analyzed.

PMID- 16466146
TI  - [Cardiac function alterations in pectus excavatum].
AB  - BACKGROUND: Cosmetic deformity and psychological repercusion are the main
      surgical indications in pectus excavatum. However cardiopulmonary function is
      subclinically abnormal in some patients. The goal of this paper is to demonstrate
      that heart response during physical activity improves after surgical correction
      of pectus excavatum. PATIENTS AND METHODS: Fifty five patients were operated upon
      for pectus excavatum during the last 10 years at our institution. Baseline
      ecocardiography and isometric effort test (Handgrip) were preoperatively
      performed in 15 patients (11 males and 4 females) aged from 6 to 15 years (median
      9,63). An increase below 12% in cardiac index was considered as positive. In
      those patients with positive tests, a new test was made 6 months after surgical
      correction. Pre and postoperative results were compared using non-parametric
      tests. RESULTS: Baseline cardiac index values were normal in all cases (11). Four
      patients were not included, 2 because of no collaboration (aged 6 and 7 years)
      and 2 because difficult ecocardiography interpretation (both operated upon for
      congenital diaphragmatic hernia). Overall, preoperative test was negative in 6
      patients and positive in the remaining 5. Postoperative test was made in these 5
      patients, and all of them showed an improvement in cardiac index (medium 40,6%,
      range 25-70) when compared to preoperative values. There was statistically
      significant association between test values and patient ages. CONCLUSIONS:
      Baseline cardiac index values were normal in children with pectus excavatum,
      albeit 45,5% of them showed a limited response to exercise. Pectus excavatum
      repair improves these values, so physiopathological indication as well as
      cosmetic one should be considered specially in children.

PMID- 16466147
TI  - [Esophageal atresia and chromosomal abnormalities in a Mexican children
      population: descriptive analysis].
AB  - INTRODUCTION: Chromosome alterations are associated with esophageal atresia (EA)
      in up to 11% of the cases. The morbidity and mortality index of this population
      is different from other EA patients. The present study was aimed to determine the
      characteristics of this association in a Mexican infant patient population.
      MATERIAL AND METHODS: Observational, descriptive, retrospective, transversal
      assay including patients with AE and chromosome alterations over a 31-year
      period. Gestational age, admittance age, sex, type of atresia, chromosome
      alteration, additional malformations, treatment, evolution and death cause, were
      registered. RESULTS: Seventeen patients (4.61%) out of 368 with EA were included.
      Chromosome 21 trisomy was detected in 12 children and 5 with 18 trisomy. One to 3
      additional malformations were found in 16 patients. Fifteen children were
      subjected to surgical procedures for EA, and 6 for associated malformations.
      Fourteen children died in a 140-day follow-up period. CONCLUSIONS: Coexistence
      between AE, trisomys and major malformations was characterized by multifactorial
      complications which determined adverse evolution in the short term.

PMID- 16466148
TI  - [Nostril retainers in the primary cleft rhinoplasty].
AB  - INTRODUCTION: The nasal cleft cartilage tends to depression after primary
      rhinoplasty. Nasal stents are probe to be useful in the management of these
      patients in order to maintain the new morphology. AIM: The purpose of this paper
      is to present our experience with the use of postoperative nasal splinting in the
      management of cleft lip nasal deformity. PATIENTS AND METHODS: A nostril retainer
      was placed in 18 cleft patients (4 bilateral, 14 unilateral) during primary
      repair of the cleft lip nasal deformity from 2001 to 2004. The nasal morphology
      in the postoperative period was compared with that of 10 control patients who
      were operated on without nasal stenting in a previous period. Nostril retainers
      were left in place after the rhinoplasty using 4/0 poliglecaprone absorbable.
      Those sutures fixed the stent in place during three weeks after surgery. Results.
      Average follow-up was 18.5 months. Retention of the splint was 3.5 months mean
      time (range 4 weeks to 6 months). The methods employed for retention were
      multiple based upon parental preferences. Photogrammetric analysis showed
      relevant asymmetry of the nostrils in 10% of the splinted group as compared with
      48% for controls (p<0.001). CONCLUSIONS: The use of nasal stents has been found
      effective postoperatively after cleft primary rhinoplasty, avoiding relapse of
      the nasal reconstruction and drop of the nasal ala. Retainers also allows airway
      patent and avoid surgical adhesions due to nasal secretions and scarring.
      Parental collaboration is needed.

PMID- 16466149
TI  - [Retroperitoneoscopic heminephrectomy].

PMID- 16466150
TI  - A vision towards a brighter future in prosthetics and orthotics.

PMID- 16466151
TI  - Development of an ankle-foot orthosis with an oil damper.
AB  - The purpose of the present study was to develop an ankle-foot orthosis (AFO) that
      satisfies the requirements for an AFO for patients with hemiplegia as determined
      in a previous study. An oil damper has been introduced as an assistive device.
      The oil damper provides a resistive moment to plantar flexion of the ankle joint
      during initial stance on the paretic side. This function improves the
      insufficient eccentric contraction of the dorsiflexors. The magnitude of the
      resistive moment generated by this newly developed AFO can be changed easily to
      adjust its properties in accordance with the requirements of each patient. The
      mechanical properties of the AFO were measured, and the results showed that the
      AFO generated a sufficient resistive moment. Hemiplegic gaits with various types
      of AFOs were assessed, and it was found that the properties of the AFO affected
      the movements of the ankle, the knee, and the hip joints. The effects of the
      resistive moment on the alignment of the shank to the floor during initial stance
      are also discussed. Based on the results of this study, it is concluded that
      adjustability will be an essential feature for future AFOs.

PMID- 16466152
TI  - Evaluation of a contemporary CAD/CAM system.
AB  - The objective of this study is to investigate the accuracy of the TracerCAD
      system in measuring a model of known dimensions and volumes. A cylindrical nylon
      6.6 model was prepared. Landmarks were added to indicate proximal, distal,
      anterior, medial, and lateral. Four additional landmarks were added at regular
      intervals along the length of the cylinder with a view to calculating diameters
      and volumes relative to these landmarks. The model was measured using a
      comparator with a guaranteed accuracy of 0.01 mm and was traced using the
      TracerCAD system (Test 1). The test was repeated with the model rotated by 90
      degrees (Test 2), to determine whether there were any effects related to the
      orientation of the model in relation to the transmitter. The difference in
      average volume between measured results and TracerCAD scans was between 0.20% and
      -1.96%. Individual trace volumes varied between -0.0085% and -4.50%. In all
      volumes measured in Tests 1 and 2, all maximum volume percentage differences
      measured greater than 3%.

PMID- 16466153
TI  - A questionnaire survey of the effect of different interface types on patient
      satisfaction and perceived problems among trans-tibial amputees.
AB  - The objectives were to investigate the effect of three different interface types
      on consumer satisfaction and perceived problems among trans-tibial amputees in
      the Netherlands. A postal questionnaire (based on the Prosthesis Evaluation
      Questionnaire) was sent to 353 patients. Responders were classified in three
      groups of interface types: polyethylene foam (PEF) inserts, silicone liners
      (SIL), and polyurethane liners (PUL). Differences concerning satisfaction and
      problems between interface types were computed and adjusted for potential
      confounding by age, gender, reason for amputation and time since first
      prosthesis. A total of 220 patients responded (62%). Patients wearing liners
      reported a significantly poorer durability and higher maintenance time compared
      with patients using PEF inserts. Sum-scores for satisfaction or problems did not
      show any significant differences between groups. Analysis of individual items
      showed a significant difference only for satisfaction with sitting and with
      walking on uneven terrain in favour of PEF inserts. In contrast to most studies,
      interface type was included as a possible determinant of customer use,
      satisfaction, and perceived problems. The perceived differences between the three
      suspension types are to a large extent small and non-significant. The findings do
      not support liner prescription as a matter of course for all trans-tibial
      amputees. A careful analysis of patients' preferences should be made to determine
      the best course of action. Further studies, preferably prospective, need to be
      conducted to determine which systems are most comfortable and offer least
      complaints.

PMID- 16466154
TI  - A cross-sectional study on the development of foot arch function of 2715 Chinese
      children.
AB  - A cross-sectional study was conducted to investigate the foot arch function of
      Chinese children. A total of 2715 children, 1246 girls, and 1369 boys, 4-18 years
      of age were recruited from kindergartens, primary, and secondary schools. The
      dynamic footprints of the children were collected using a portable pressure
      sensing mat. The Contact Force Ratio (CFR, i.e. the ratio of the mid-foot loading
      to the total loading of the contacted foot, with the toes ignored) of each age
      group was calculated. In general, the CFR decreased from 4 to 10 years and
      plateaued at 10-12 years and then increased until 15-16 years. An abnormal low
      arch foot was defined as the foot that had a CFR value larger than the
      corresponding age mean plus one standard deviation. The cut-off CFR values of
      each age group were calculated. With the exception of the 17 years age group,
      which consisted of a relatively small number of subjects, the percentage of low
      arch subjects of all the other age groups ranged from 15 to 20%.

PMID- 16466155
TI  - Usability of gait analysis in the alignment of trans-tibial prostheses: a
      clinical study.
AB  - The purpose of the study was to investigate which systematic effects of
      prosthetic misalignment could be observed with the use of the SYBAR system. The
      alignment of the prosthesis of five well-trained unilateral trans-tibial amputees
      was changed 15 degrees in magnitude in varus, valgus, flexion, extension,
      endorotation, exorotation, dorsal flexion, and plantar flexion. Subjects walked
      over a distance of 8 m at a self-selected walking speed with the alignment of the
      prosthesis as it was at the start of the experiment (reference) and with each
      changed alignment. Two video cameras (frontal and sagittal) and a force plate of
      the SYBAR system (Noldus Information Technology, The Netherlands) were used to
      capture gait characteristics of the subjects. Temporal and spatial
      characteristics, the magnitude and timing of the ground reaction force (GRF), and
      the external joint moments were derived from these data. Despite the substantial
      perturbations to prosthetic alignment, only a few effects were observed in the
      temporal and spatial characteristics of gait, the magnitude and timing of the
      GRF, and the external joint moments. Only the pattern of the ground reaction
      force in the mediolateral direction and the joint moment around the ankle in the
      frontal plane during terminal stance showed a systematic effect when the
      alignment was set into varus and valgus or exorotation. It was concluded that
      using the SYBAR system in this study revealed little effect of perturbations in
      prosthetic alignment, for this group of patients, and for the selected
      parameters. It was questioned whether this is due to the relatively low
      resolution of the SYBAR system or the capacity of the well-trained subjects to
      compensate for the disturbance in alignment. It was suggested that the usability
      of the SYBAR system in clinical settings should be further explored.

PMID- 16466156
TI  - Gait of stance control orthosis users: the dynamic knee brace system.
AB  - Individuals with weak or absent quadriceps who wish to walk independently are
      prescribed knee-ankle-foot orthoses (KAFOs). New stance control orthosis (SCO)
      designs automatically release the knee to allow swing phase flexion and extension
      while still locking the joint during stance. Twenty-one participants were fitted
      unilaterally with the Dynamic Knee Brace System (DKBS), a non-commercial SCO.
      Thirteen subjects were experienced KAFO users (average 28 +/- 18 years of
      experience) while eight were novice users. Novice users demonstrated increased
      velocity (55 vs. 71 cm/sec, p = 0.048) and cadence (77 vs. 85 steps/min, p <
      0.05) when using the DKBS over the traditional locked KAFO. Experienced KAFO
      users tended to have reduced velocity and cadence measures when using the SCO (p
      < 0.10). Knee range of motion was significantly greater for the novice group than
      for the experienced group (55.2 +/- 4.8 vs. 42.6 +/- 3.8 degrees, p = 0.05). Peak
      knee extension moments tended to be greater for the experienced group (0.29 +/-
      0.21 vs. 0.087 +/- 0.047 Nm/kg, p = 0.09). This report describes gait changes
      during the introductory phase of DKBS adoption. Experienced KAFO users
      undoubtedly had ingrained gait patterns designed to compensate for walking with a
      standard locked KAFO. These patterns may have limited the ability of those users
      from taking full and immediate advantage of the SCO capabilities. Also, alternate
      SCO systems may engender different results. Comparison studies and longer term
      field studies are needed to clarify benefits of the various bracing options.

PMID- 16466158
TI  - A photoelastic clinical study of the static load distribution at the stump/socket
      interface of PTB sockets.
AB  - It is recognized that the assessment of prosthetic socket fit is based largely on
      the subjective clinical judgement of the prosthetist. This study assesses a novel
      technique, photoelasticity, for use as a tool for the qualitative and
      quantitative assessment of socket fit. Photoelasticity is a visual technique that
      produces contours of principal stress or strain differences. The colour and/or
      distance between the contours can be qualitatively or quantitatively assessed,
      using a polariscope, to give a full-field analysis of the stresses on the
      sockets's surface. This paper presents qualitative photoelastic socket surface
      contour data gathered during several prosthesis fitting sessions for two male
      trans-tibial amputees. Results are compared with the actual known contact regions
      at the stump/socket interface to determine if a relationship exists. This
      comparison of results has then been used to conclude the suitability of
      photoelasticity as a tool for the assessment of socket fit and recommendations
      are made as to the future developments of the technique. A direct relationship
      between the stump/socket contact regions and the qualitative photoelastic
      contours was demonstrated. Given further development this photoelastic technique
      may therefore be suitable for qualitative analysis of the interactions between
      the stump and prosthetic socket.

PMID- 16466157
TI  - Skew flap technique in trans-tibial amputation.
AB  - The long posterior flap technique is an established technique for trans-tibial
      amputation in ischaemic limbs. Despite its success, it has a few drawbacks. It
      may be time-consuming and requires considerable planning, and at times the dog
      ears cannot be avoided. The suture line passes over the distal end of the stump,
      which is usually a problem during prosthetic use. The skew flap technique retains
      the advantages of the long posterior flap technique and eliminates the
      difficulties of prosthetic fitting. The equal skin flaps are skewed so that the
      flaps become anteromedial and posterolateral, whereas the calf muscle flap
      remains long underneath the skewed skin flaps. The posterior muscles are brought
      anteriorly covering the cut ends of the bones and are buried in between the tibia
      and its anterior periosteum, by suturing their margins with the periosteum. The
      skew flap procedure was perceived in 1980 and was started at the Artificial Limb
      Centre, Pune in 1983 by the author. This procedure underwent many changes during
      the initial 5 years and by the end of April 1992, 85 trans-tibial amputations
      were performed using this technique. A 9-year follow-up of these patients, who
      had been using prostheses with ease and without any discomfort or problem, had
      been exceptionally good. Encouraged by the results, this technique is now being
      practised as routinely. By March 1998, a total of 125 such trans-tibial
      amputations had been performed in 119 patients, with excellent results.

PMID- 16466159
TI  - Development of a novel type of shoe to improve the efficiency of knee-ankle-foot
      orthoses with a medial single hip joint (Primewalk orthoses): a novel type of
      shoe for Primewalk orthosis.
AB  - The purpose of the study was to develop and evaluate a new heel cushion in shoes
      for use with knee-ankle-foot orthoses having a medial single hip joint (Primewalk
      orthoses) in order to improve walking velocity and efficiency. Primewalk orthoses
      and shoes were made for a 24-year-old man having paraplegia with flaccid paresis
      (level T-7; grade A, ASIA impairment scale) of 2 years' duration. Walking
      exercises were assigned. Shoes were modified with the sole made of hard rubber
      and the addition of soft rubber heel cushions. The walking speed, centre of foot
      pressure during walking, and ground reaction force were evaluated. The patient
      also subjectively assessed the devices. The modifications to the shoes resulted
      in a 1.94-fold increase in walking speed (8.6 to 16.7 m/min), a 1.87-fold
      increase in step length (16.7 to 31.3 cm) and a 54.8% decrease in the
      physiological cost index (7.7 to 3.48 beats/min). The centre of foot pressure
      during walking was found to deviate towards the lateral margin of the foot. The
      horizontal rotation of the pelvis increased simultaneously. The patient reported
      increased amplitude of flail motion of the trunk and decreased burden to the
      upper limbs. It was concluded that the modified new heel cushion of the shoe
      provided freedom to the lower legs and thereby increased walking efficiency.

PMID- 16466161
TI  - [Play superior role of integrative medicine thought for further improving
      clinical efficacy of traditional Chinese medicine against hepatic fibrosis].

PMID- 16466160
TI  - [Progress in non-invasive diagnostic model of hepatic fibrosis].

PMID- 16466162
TI  - [Therapeutic strategy on hepatic fibrosis].

PMID- 16466163
TI  - [Traditional Chinese medicine treatment of hepatic fibrosis and its
      characteristics].

PMID- 16466164
TI  - [Current status of research on basic theory of hepatic fibrosis].

PMID- 16466165
TI  - [Clinical study on effect of xiongshao capsule on restenosis after percutaneous
      coronary intervention].
AB  - OBJECTIVE: To further evaluate the effect of Xiongshao Capsule (XSC) on the
      restenosis (RS) after percutaneous coronary intervention (PCI), based on previous
      clinical trials by which the preventive effect of XSC on RS after PCI has been
      proved. METHODS: Adopting the randomized, double-blind and placebo controlled
      method, the 124 patients enrolled, who were patients with coronary artery disease
      and received intracoronary stenting, were randomly assigned into two groups, the
      XSC group and the placebo control group, with 62 in each group. Six months of
      follow-up study was carried out on them to observe the intervention effect of
      XSC, which was predominantly evaluated by RS rate estimated by coronary
      angiography (CAG), combined with the recurrent rate of angina, clinical end-point
      event, and blood-stasis syndrome scores. RESULTS: Sixty two cases of 118
      effective patients were followed-up with CAG for 6 months, the follow-up rate was
      52.5%. The incidence of RS in the XSC group and the control group was 24.1% and
      48.5% respectively, and the incidence of RS in stent in them was 14.0% and 42.0%
      respectively, indicating that the incidence of RS rate in the XSC group was
      significantly lower than that in the control group (P < 0.05). After patients had
      been treated for 6 months the extent of angiostenosis and diameter of the culprit
      arteries, determined by CAG was 26.58 +/- 20.72% and 2.21 +/- 0.85 mm in the XSC
      group, and 41.19 +/- 30.92% and 1.72 +/- 0.99 mm in the control group,
      respectively, suggesting that the extent of angiostenosis and the diameter loss
      were significantly reduced in the former than those in the latter, respectively
      (P < 0.05). The incidence of clinical end-point event was 11.7% and 27.6% in the
      XSC group and the control group in the 6 months' follow-up period respectively,
      it was significantly lower in the XSC group than that in the control group, with
      the P value close to statistical significance (P = 0.051). The blood-stasis
      syndrome scores in the XSC group was significantly lower in comparing with that
      in the control group after 6 months' treatment (P < 0.01). CONCLUSION: XSC can
      effectively prevent RS after PCI in combination with conventional Western medical
      treatment.

PMID- 16466166
TI  - [Investigation on indication of fuzheng huayu capsule against hepatic fibrosis
      and its non-invasive efficacy evaluation parameters: data analysis of liver
      biopsy of 50 patients with chronic hepatitis B before and after treatment].
AB  - OBJECTIVE: To investigate the indication of Fuzheng Huayu Capsule (FHC) against
      hepatic fibrosis and its non-invasive efficacy evaluation parameters. METHODS:
      Data involving hepatic fibrotic patients received twice liver biopsy before and
      after FHC treatment were received from multi-center, randomized, double-blind,
      controlled clinical trials and analyzed. The changes of indexes related to
      inflammation of hepatic tissue and liver function, serological and virologic
      parameters of fibrosis, blood routine test, hepatic ultrasonic test as well as
      clinical symptoms and signs of patients were compared between patients alleviated
      (assigned to the effective group) and un-alleviated (assigned to the ineffective
      group) by the treatment. RESULTS: (1) The degree of liver fibrosis, ALT activity
      and the scores of symptoms of hypochondriac pain and dry mouth before treatment
      were remarkably higher in the effective group than those in the ineffective
      group. (2) Level of ALT activity decreased in both groups after treatment. In the
      effective group, the grading scores of hepatic inflammatory significantly
      decreased after treatment (P < 0.01), levels of AST and GGT decreased after 3
      months' treatment, and levels of GGT and PT significantly decreased after treated
      for 6 months, as compared to those in the ineffective group, showing significant
      difference. (3) Levels of serum hyaluronic acid (HA) and collagen type III (P-III
      P) remarkably decreased after 12 weeks' treatment in the effective group. (4)
      Symptoms and signs were improved at various degrees in the two groups, but the
      improvement in dim and blackish complexion was more significant in the effective
      group than that in the ineffective group. (5) The changes in virologic parameters
      of hepatitis B virus, blood routine and hepatic ultrasonic test between the two
      groups showed no significant difference respectively. CONCLUSIONS: (1) FHC showed
      better effect against hepatic fibrosis in patients of fibrotic stage around S3,
      with obvious active hepatic inflammation and symptoms of hypochondriac pain and
      dry mouth, which could be taken as a referential index in clinical practice for
      indication decision. (2) The increase of serum albumin, decrease of GGT, AST, PT,
      HA, and P-III-P as well as the improvement of signs of dim and blackish
      complexion could be regarded as the referential indexes of effectiveness of FHC
      against hepatic fibrosis. These parameters are valuable non-invasive indices for
      diagnosis of hepatic fibrosis and efficacy evaluation of its treatment.

PMID- 16466167
TI  - [Clinical study on effect of bushen granule combined with marine injection in
      treating chronic hepatitis B of Gan-shen deficiency with damp-heat syndrome
      type].
AB  - OBJECTIVE: To evaluate the antiviral efficacy of Bushen Granule (BSG) combined
      with Marine Injection (MI) in treating patients with chronic hepatitis B of Gan
      shen deficiency with Damp-Heat (GSD) syndrome type. METHODS: A total of 90
      patients, who were HBV DNA, HBsAg, and HBeAg positive and of GS-DD type, were
      enrolled, and they were randomly assigned into 2 groups. The 49 patients in the
      treated group were treated with the combined therapy of BSG and MI and the 41
      were administered with lamivudine, the therapeutic course for both groups was 1
      year. The negative conversion rate of HBeAg and HBV DNA and the changes in HBV
      DNA titre, liver function, symptoms and physical signs were observed in the two
      groups before and after treatment. RESULTS: In the treated group, the negative
      conversion rate of HBV DNA was 42.6% (20/ 47), insignificantly different to that
      in the control group (61.0%, 25/41, P > 0.05); the negative conversion rate of
      HBeAg and HBeAg/anti-HBe sero-conversion rate was 42.6% and 36.2%, respectively,
      significantly higher than those in the control group (22.0% and 17.0%, P < 0.05);
      the ALT normalizing rate was 74.4%, higher than that in the control group (51.4%,
      P < 0.05); the improvement of liver function (ALB and GLB) and clinical symptoms,
      especially the dizziness, soreness of waist, hypochondrial distending pain, and
      yellowish urine, were significantly superior to those in the control group(P <
      0.01 or P < 0.05); and the partial response rate was 29.8%, insignificant
      different to that in the control group (14.6%, P > 0.05). CONCLUSIONS: Combined
      treatment of BSG and MI has an ideal short-term effect in treating patients with
      chronic hepatitis B of Gan-shen deficiency with Damp-Heat syndrome type, it can
      inhibit HBV replication and improve patients' liver function and physical signs.

PMID- 16466168
TI  - [Clinical efficacy of treatment for regulating Pi and protecting Xin in treating
      patients after coronary artery bypass grafting and its effect on patients'
      quality of life].
AB  - OBJECTIVE: To evaluate the clinical efficacy of treatment for regulating Pi and
      protecting Xin (abbr. as CHM) and its effect on quality of life (QOL) in patients
      after coronary artery bypass grafting (CABG). METHODS: One hundred and six
      patients, who were planned to undergo CABG were assigned into two groups, the 51
      patients in the control group were treated with conventional Western medicinal
      treatment (WM) and the 55 patients in the experimental group were treated by WM
      with additional medication of CHM constituted mainly by modified Huxin Recipe.
      The changes of symptoms and heart function were observed and the patients' QOL
      was evaluated by SF-36 Scale. RESULTS: After being treated for 3 months, the
      total scores of symptoms in the experimental group was significantly improved in
      comparing with that in the control group (P < 0.01), the clinical efficacy on
      symptoms of TCM and improvement of heart function were superior to those in the
      control group (P < 0.05) respectively. The scores in terms of pain, vitality,
      role of emotion, mental health, health transition of patients in the experimental
      group according to SF-36 scale were significantly higher than those in the
      control group (P < 0.05 or P < 0.01). CONCLUSION: Treatment for regulating Pi and
      protecting Xin by modified Huxin Recipe can improve the recovery process of
      patients after CABG, elevate patients' heart function, symptoms and QOL.

PMID- 16466169
TI  - [Evaluation on effect of feiji recipe on quality of life of patients with non
      small cell lung cancer by adopting international questionnaire of QOL].
AB  - OBJECTIVE: To evaluate the effect of Feiji Recipe (FJR) on quality of life (QOL)
      of patients with non-small cell lung cancer (NSCLC). METHODS: One hundred and two
      patients with NSCLC were randomly assigned into 2 groups. The 61 patients in the
      combined treated group were given FJR and chemotherapy and the 41 patients in the
      control group were treated with chemotherapy alone. They were observed for two
      treatment courses with QOL estimated by EORTC QLQ-C43 questionnaire and FACT-L
      questionnaire, the two international questionnaires as the tools for measurement,
      and referred to the traditional evaluating indexes of clinical efficiency.
      RESULTS: QOL in the combined treated group was improved after treatment with the
      improvement of scores in all domains, including functional and symptom sub
      domain, while it in the control group deprived significantly, showing significant
      difference between the two groups (P < 0.05). Similar results were also shown in
      the evaluation of physical performance by Eastern Cooperative Oncology Group
      (ECOG) and Karnovfsky performance scoring. The gastrointestinal reaction and
      myelo-suppression were slighter in the combined treated group than those in the
      control group (P < 0.05), and no significant difference was shown between the
      response rate of the two groups (P > 0.05). CONCLUSION: FJR can improve QOL of
      patients with NSCLC, reduce the adverse reaction of chemotherapy, and improve
      patients' physical performance.

PMID- 16466170
TI  - [Study on the relationship between polymorphism of ApoE gene and TCM syndrome
      type of primary hyperlipemia].
AB  - OBJECTIVE: To study the relationship between the polymorphism of ApoE gene and
      TCM syndrome type of primary hyperlipemia. METHODS: ApoE genotype of 102 patients
      with hyperlipemia was detected by gene PCR sequencing. RESULTS: A total of five
      genotypes were detectable, they were E2/2, E3/3, E4/4, E2/3 and E3/4. The
      frequency of E3/4 + E4/4 and epsilon4 allelotype detected in the patients of Gan
      Shen Yin deficiency syndrome type were significantly higher than those in
      patients of Pi-Shen Yang-deficiency type or of phlegm stagnation type (P < 0.05,
      P < 0.01), and which in patients of Qi-stagnation caused blood stasis type were
      significantly higher than those in patients of phlegm stagnation type ( P <
      0.05). CONCLUSION: Polymorphism of ApoE gene is related in a certain degree to
      TCM syndrome type of primary hyperlipemia.

PMID- 16466171
TI  - [Clinical observation of daidzein intervention on serum inflammatory factors in
      senile patients with coronary heart disease].
AB  - OBJECTIVE: To observe the effect of daidzein on serum inflammatory factors of
      senile patients with coronary heart disease (CHD). METHODS: Forty senile patients
      with CHD were randomly assigned into the control group and the daidzein group, 20
      in each group. Patients in both groups were treated with conventional medicine,
      while those in the daidzein group were given daidzein Tablets additionally for 6
      weeks. The levels of resting heart rate (RHR), blood pressure (BP), fasting
      plasma glucose (FPG), blood lipids and inflammatory factors, including hsCRP, IL
      6 and TNF-alpha, were measured before and after treatment. RESULTS: In the
      control group, the levels of RHR, BP and hsCRP changed after conventional
      medicinal treatment (P < 0.05 or P < 0.01) but other parameters unchanged (P >
      0.05). While in the daidzein group, all the parameters measured were decreased in
      different degrees after 6 weeks treatment (P < 0.05 or P < 0.01), and also showed
      significant difference as compared with those in the control group respectively
      (P < 0.05 or P < 0.01). CONCLUSION: Daidzein can effectively decrease the levels
      serum inflammatory factors in senile patients with CHD, the fact proved that
      isoflavone has anti-inflammatory effect in patients with coronary
      atherosclerosis.

PMID- 16466172
TI  - [Clinical effect of treatment for clearing heat, detoxicating and nourishing Yin
      on patients with glucocorticosteroid induced facial dermatitis and its effect on
      skin barrier function].
AB  - OBJECTIVE: To observe the clinical efficacy of treatment for clearing heat,
      detoxicating and nourishing Yin (abbr. as CHM) on glucocorticosteroid (GCS)
      induced facial dermatitis, and its effect in repairing skin barrier function.
      METHODS: One hundred and fifteen patients were randomly assigned into two groups,
      68 in the treated group treated with CHM and 47 in the control group treated by
      oral administration of loratadine 10 mg once a day and ketotifen 1 mg once every
      night. The volume of transepidermal water loss (TEWL) of patients was measured
      before and after treatment. RESULTS: The effective rate was 77.9% (53/68) and
      14.9% (7/47) in the treated group and the control group respectively, showing
      significant difference between the two groups, and it was better in the treated
      group than that in the control group (P < 0.01). The decrease of TEWL in the
      treated group was also superior to that in the control group (P < 0.01).
      CONCLUSION: Chinese herbal treatment for clearing heat, detoxicating and
      nourishing Yin has significant clinical efficiency on GCS induced facial
      dermatitis and in repairing the skin barrier function.

PMID- 16466173
TI  - [Effect of tongxinluo ultramicro-pulverization on myocardial post-reperfusion no
      reflow in mini-swine model of acute myocardial infarction].
AB  - OBJECTIVE: To assess the effect of Tongxinluo (TXL) ultramicro-pulverization in
      preventing and treating post-reperfusion no-reflow in mini-swine model of acute
      myocardial infarction. METHODS: Forty mini-swines were randomly divided into 5
      groups, the control group, the three (low-, middle- and high-dose) TXL groups and
      the sham-operation group, with 8 in each group. After pigs in the three TXL
      groups were administered with TXL in a dose of 0.05g/kg, 0.2g/kg and 0.5g/kg once
      a day for 3 days respectively, they were made into acute myocardial
      ischemia/reperfusion model by ligating left anterior descending coronary artery
      for 3h followed with 1h of untying. Hemodynamic examination and myocardial
      contrast echocardiography (MCE) were conducted before and after ligation, and
      after reperfusion, finally, pathological analysis was done. RESULTS: Post
      reperfusion ventricular function injury was significantly improved in the three
      TXL groups, as compared with the control group, the no-reflow area determined by
      hemodynamic and MCE decreased from 78.5 +/- 4.4% and 82.3 +/- 1.9% in control to
      43.4 +/- 3.2% and 44.6 +/- 3.3% (low-dose), 25.2 +/- 2.4% and 25.7 +/- 4.0%
      (middle-dose), 24.0 +/- 1.9% and 24.9 +/- 4.2% (high-dose), respectively (P <
      0.05 or P < 0.01), and the myocardial infracted area was reduced from 98.5 +/-
      1.4% to 89.8 +/- 4.6%, 80.2 +/- 3.1% and 79.9 +/- 3.1%, respectively (P < 0.05, P
      < 0.01). CONCLUSION: TXL ultramicro-pulverization can effectively prevent and
      treat no-reflow after myocardial acute infarction following reperfusion, and
      reduce the infracted area.

PMID- 16466174
TI  - [Effect of GETO on expression of protein in postsynaptic dense zone of
      Alzheimer's disease model rats].
AB  - OBJECTIVE: To observe the effect of GETO on expression of PSD-95 and Shank-1
      protein in postsynaptic dense zone in Alzheimer disease (AD) model rats. METHODS:
      The AD model rats were established by beta-amyloid protein (Abeta(1-42))
      injection into hippocampus CA1 zone. They were assigned into the model group, the
      donepezil treated group and the GETO treated group, besides, a normal group was
      set for control. Four weeks after modeling, Morris water maze test was applied to
      determine the learning and memory function of the AD rats, the number of PSD-95
      and Shank-1 protein positive neuron as well as the optical density (OD) in post
      synaptic dense zone of hippocampus CA1 area were determined by using immuno
      histochemical stain and computerized graphic analysis techniques. RESULTS: Morris
      water maze test showed that the mean escape latent period (MELP) of the model
      rats obviously prolonged than that of the normal rats, and the times of
      traversing flat roof obviously decreased (P < 0.01), while in the model rats
      after being treated by GETO, the two parameters were significantly shortened and
      increased respectively (P < 0.01), reaching the level insignificantly different
      to those in the donepezil group and the normal group. Immunohistochemical test
      showed that the number of positive stained neuron of PSD-95 and Shank-1 in
      hippocampus CA1 zone in the model group was significantly different to those in
      the normal group (P < 0.01), while in the GETO group those indexes were
      insignificantly different to those in the donepezil group and the normal group (P
      > 0.05), but showed a significant difference when compared with those in the
      model group (P < 0.05). CONCLUSION: GETO can obviously improve the function of
      learning and memory of AD rats induced by Abeta(1-42), and the mechanism may be
      associated with its actions in improving expressions of PSD-95 and Shank-1
      protein in hippocampus CA1 zone, and recovering the structure and function of
      synapse and enhancing its plasticity.

PMID- 16466175
TI  - [Experimental study on mechanisms of lyophilized powder of fresh gekko Chinenis
      in inhibiting H22 hepatocarcinoma angiogenesis].
AB  - OBJECTIVE: To investigate the inhibitory effects and its mechanism of lyophilized
      powder of fresh Gekko Chinenis (GCLP) on H22 hepatocarcinoma growth and
      angiogenesis in vitro. METHODS: The transplant tumor model of H22 hepatocarcinoma
      in mice was established. Thirty mice were randomly divided into three groups, the
      cisplatin group, the GCLP group and the control group, they were treated
      respectively with intraperitoneal injection of cisplatin 1 mg/g, oral
      administration of GCLP in a dose of 1.2 g/kg, and equal volume of saline, the
      medication was given for 20 times totally. The anti-tumor activity was evaluated
      by tumor tissue weighing, the cell apoptotic rate was detected by TUNEL method,
      the micro-vessel density in tumor tissue was determined by Weidner method, the
      protein expression of vascular endothelin growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) were detected by S-P immunohistochemistry.
      RESULTS: GCLP could obviously inhibit the hepatocarcinoma growth, induce tumor
      cell apoptosis, and reduce micro-vessel density in tumor tissue through down
      regulating VEGF and bFGF protein expression. CONCLUSIONS: GCLP can effectively
      inhibit the growth of H22 hepatocarcinoma and angiogenesis. Its mechanism might
      be related to the down-regulation of the protein expression of VEGF and bFGF.

PMID- 16466176
TI  - [Experimental study of liver fibrosis reversal effect of warming-yang compound
      formula ganzhifu].
AB  - OBJECTIVE: To observe the effect of Ganzhifu (GZF), a Chinese compound formula
      for Warming-yang on experimental hepatic fibrosis, and to explore its mechanism.
      METHODS: Fifty-nine Wistar rats were divided into the normal control group and
      the model group. After the hepatic fibrosis model was established in rats by
      subcutaneous injection of CCl4 and feeding 10% alcohol in the model group, the
      rats were randomly sub-divided into the Ganzhifu group, colchicine group and
      model group, they were treated with Ganzhifu, colchicine and normal saline of
      same volume once a day respectively for 30 days as one treatment course. The
      serum liver function and hepatic fibrosis indexes, liver tissue contents of
      hydroxyproline (Hyp), malondialdehyde (MDA) and superoxide dismutase (SOD)
      activity were measured at the end of the experiment. Histologic changes of liver
      tissue were observed and scored by the modified inflammatory activity and
      fibrosis semiquantative scoring system (SSS), and collagen type I , III and IV in
      liver tissue were stained and semiquantitive analysis conducted. RESULTS: In the
      Ganzhifu group, liver function and inflammatory activity and fibrosis SSS scores
      were markedly improved, indexes of hepatic fibrosis, liver contents of Hyp, MDA
      and collagen type I, III and IV were significantly decreased, and the SOD
      activity was increased, the changes were more significant as compared with those
      in the model group. The protective effect of Ganzhifu against hepatic fibrosis
      was the same as that of colchicine. CONCLUSION: Ganzhifu can alleviate or reverse
      hepatic fibrosis in experimental hepatic fibrosis, and antioxidation may be its
      mechanism.

PMID- 16466177
TI  - [Protective effect of epimedium flavonoids injection on experimental myocardial
      infarction rats].
AB  - OBJECTIVE: To investigate the protective effect of epimedium flavonoids Injection
      (EFI) on experimental acute myocardial infarction (AMI) rats. METHODS: Rats were
      randomly divided into 6 groups, the acute myocardial infarction model was
      established by ligating left anterior descending branch of coronary artery (LAD).
      After operation, the rats in the sham-operation and model group were intravenous
      injected with 5% glucose injection, those in the positive medicine group were
      intravenous injected with nitroglycerin 0.3mg/kg, while rats in the low-, middle-
      and large-dose EFI group were intravenous injected with TFE in a dose of 10, 20,
      40 mg/kg respectively. ECG was monitored before and after coronary artery
      ligation, and after treatment at different time points. At the same time, the
      millivolt of ST and ST-T segment were measured. The changes of serum creatine
      phosphokinase (CPK), lactate dehydrogenase (LDH), superoxide dismutase (SOD)
      activity and malondialdehyde (MDA) content were determined, and the myocardial
      infarcted area was detected by MTT respectively 3 h after LAD. Results After
      intravenous injection of EFI in a dose of 10, 20, 40 mg/kg, the myocardial
      infarcted area of AMI rats could be decreased in different degree, the activity
      of serum CPK, LDH and the content of MDA decreased (P < 0.05 or P < 0.01), while
      the activity of serum SOD increased significantly (P < 0.05 or P < 0.01). It
      could began to lower the elevated ST-T segment 5 min after medication and the
      action could last for 3 h (P < 0.05 or P < 0.01). CONCLUSION: EFI has a
      protective effect against acute myocardial ischemia caused by LAD, and the effect
      is quickly initiated.

PMID- 16466178
TI  - [Clinical observation on effect of tiaozhi jiangtang tablet on patients with
      diabetes of blood stasis syndrome: a report of 30 cases].
AB  - OBJECTIVE: To observe the clinical efficacy of Tiaozhi Jiangtang Tablet (TZJT) on
      patients suffering from diabetes mellitus with blood stasis syndrome. METHODS:
      Sixty patients were randomly assigned into 2 groups, the TZJT group (n = 30)
      treated with TZJT tablet and asprin, the control group (n = 30) treated with
      asprin alone. RESULTS: The improvement of symptoms was more significant in the
      TZJT group than that in the control group (P < 0.05). Levels of serum endothelin
      (ET), nitric oxide (NO) content and blood viscosity were decreased in both groups
      after treatment, and the effect of TZJT plus asprin was superior to that of
      asprin alone. CONCLUSION: TZJT combined with asprin is effective in improving the
      serum content of ET and NO and reducing blood viscosity.

PMID- 16466179
TI  - [Clinical observation on effect of yishen jianpi huayu decoction in treating
      chronic renal insufficiency].
AB  - OBJECTIVE: To observe the therapeutic effect of Yishen Jianpi Huayu Decoction
      (YJHD) in treating chronic renal insufficiency (CRI). METHODS: Forty-three
      patients with CRI were selected and randomly assigned into two groups, the 24
      patients orally administered with YJHD in the treated group and the 19
      administered with coated aldehyde oxystarch in the control group, the therapeutic
      course was 2 months. The symptom, physical sign, kidney function, blood lipids of
      patients were observed before and after treatment and the comprehensive clinical
      efficacy of the treatment was evaluated. RESULTS: The total effective rate was
      87.5% and 52.6% in the two groups respectively, it was significantly higher in
      the treated group than that in the control group (P < 0.05). The improvement of
      kidney function, blood lipids, and hemorrheologic parameters in the treated group
      were superior to those in the control group (P < 0.05). CONCLUSION: YJHD is
      effective in treating chronic renal insufficiency.

PMID- 16466180
TI  - [Application of non-randomized study in the field of traditional Chinese medicine
      or integrated traditional Chinese and Western medicine].
AB  - Non-randomized studies (NRS) have gradually attracted people's attention in the
      field of clinical medicine. In this paper, the importance of NRS was emphasized
      on the viewpoints of the coherence of scientific research, the limitation of
      randomized control trials (RCTs), the immanent characteristics of TCM clinical
      practice and the actual requirement of complex intervention in clinical practice.
      And two main points in evaluation and implementation of NRS differed to those in
      RCTs were put forward, i.e. the first, the full-scale design of the study with
      the professional characteristics should be described very explicitly, especially
      the speciality of the objects, intervention elements and indexes for
      effectiveness evaluation, etc.; the second, the control of bias and evaluation of
      effectiveness, and their influence on conclusion induction should be fully taken
      into consideration. At the same time, the key step in improving the quality of
      NRS of TCM and integrative medicine was preliminary discussed in this paper.

PMID- 16466181
TI  - [Some thoughts on studying essence of syndromes based on genomics].
AB  - In the postgenomic era, the contents of methodology of human genomics researching
      is similar to the views of holism and syndromes differentiation of traditional
      Chinese medicine. So far, many scholars have probed beneficially into the essence
      of syndrome on the gene level. Since the syndrome of TCM have close intrinsic
      relations with not only the difference of gene expression but also the gene
      polymorphisms, therefore, it is capable, taking this as a cut-in point, to
      clarify the essential of syndrome by fully applying the advanced experimental
      methods and detecting techniques to deeply investigate the gene difference
      expression spectra based on the study of the relationship between gene
      polymorphisms and syndrome susceptibility, and analyze the regulatory network of
      the related genes from the view of functional genomics.

PMID- 16466182
TI  - Vancouver Island Health Authority (VIHA) in house Perioperative Nursing Program.
AB  - The Vancouver Island Health Authority (VIHA) in liaison with the University of
      Victoria (UVIC) offers an introduction to Perioperative Nursing Program to 4th
      Year undergraduate nursing students. The aim of this program is to help recruit
      Registered Nurses to the Operating Room. It has been advantageous to the
      recruitment and retention of nurses graduating from UVIC. Its importance is
      increased by the fact that a significant quantity of Victoria's perioperative
      nurses will be retiring in the next few years. Due to the high cost of nursing
      education and the financial investment that has already been committed by nursing
      students, the Perioperative nursing program is free to the student as the program
      can be included, for the successful candidate, as part of the UVIC nursing
      course. The intention is to encourage participation by reducing the financial
      burden, stress, and anxiety for the new graduate who intends to specialize. In
      return, the student is required to work in the VIHA for a minimum of one year,
      thus supporting the retention efforts of the hospital. For eligible nursing
      students, this program provides access to extensive perioperative nursing
      experience. Over the course of 3 months they are exposed to extensive theory in a
      classroom setting as well as clinical practice through a preceptorship program.
      The mentoring relationships that develop between perioperative nurses and
      students lead to meaningful relationships and professional growth for staff. The
      perioperative focus of the program improves the knowledge and skill set of
      nursing students. The intent is to increase nursing student's interest in
      pursuing a career as a perioperative nurse and to help ensure continued growth of
      the perioperative nursing profession in Victoria.

PMID- 16466183
TI  - 10 years of perioperative nursing certification.

PMID- 16466184
TI  - Positive radiance--the aura becomes you!
AB  - Visualize your positive vibes penetrating the tough alligator skin of the
      downtrodden "crankies". By warming their sad soul even just a few degrees a day
      it will slowly, but surely, improve their attitude and your life. Imagine the
      strength of a "gang" of positive attitudes and what they could accomplish. Make
      it your agenda to develop a consistent and strong positive attitude. Use your
      mind to create a satisfying aura that will surround you in a positive light. We
      need positive attitude to surround us all! Make it so!

PMID- 16466185
TI  - Nurse First Surgical Assistant (NFSA)--a rewarding career.
AB  - In the wide field of nursing specialities, there is one that captured our
      interest; Registered Nurse First Assistant (RNFA). In Quebec this is a new
      profession (known as Nurse First Surgical Assistant or NFSA) so the author has
      written about the progression that has been achieved, a description of the role,
      a brief update about its present situation and finally a word about what the
      future holds.

PMID- 16466187
TI  - Cochlear implants: an update.

PMID- 16466188
TI  - Relationships among professionals' knowledge, experience, and expectations
      regarding cochlear implants.
AB  - THE PRESENT STUDY examined the relationships between teachers' and communication
      clinicians' self-reported knowledge on cochlear implants and their expectations
      of CIs. The authors also explored these professionals' views regarding the
      child's communication mode, educational setting, and social options following
      cochlear implantation. The participants were 47 teachers of deaf students and 35
      communication clinicians. The results showed that there were no significant
      differences between the two groups in self-reported knowledge on CI. Both groups
      knew very little about mapping, costs, or insurance, and reported good knowledge
      about candidacy. Expectations from CIs were moderate to high, and were
      significantly related to respondents' knowledge and specific experience with CIs.
      Most professionals in both groups supported spoken-language communication,
      individual inclusion, and social exposure to children with normal hearing as well
      as to children with hearing impairments.

PMID- 16466189
TI  - Perceptions of diverse educators regarding ethnic-minority deaf college students,
      role models, and diversity.
AB  - IN A QUALITATIVE STUDY, the researchers documented the perceptions of deaf and
      hearing ethnically diverse university faculty and staff regarding issues related
      to the education of ethnic-minority deaf college students. These experienced
      educators commented on the importance of ethnic-minority role models for deaf
      college students, the academic preparedness of ethnic-minority deaf students,
      these students' level of comfort on campus, and the success of institutional
      efforts to increase awareness regarding ethnic diversity. The insightful
      reflections of these diverse educators can be informative in improving the
      educational experience of ethnic-minority deaf students.

PMID- 16466190
TI  - A mixed-methods study of teachers of the deaf learning to integrate computers
      into their teaching.
AB  - A MIXED-METHODS STUDY was conducted of 47 teachers of the deaf in seven urban and
      suburban programs around the country as they participated in an online training
      program. The goal of the training program was to encourage the teachers to
      integrate technology into their teaching of children who were deaf or hard of
      hearing. In their evaluation of the project, the researchers sought to identify
      factors that supported the success of the program. Data used in the evaluation of
      the project were drawn from responses to formal questionnaires, information on
      retention in the program, and an analysis of comments during online asynchronous
      discussions. Anxiety about using technology, access to technology, and initial
      expertise did not determine whether teachers were retained in the program;
      however, the degree of local support for participants did differentiate those who
      continued in the program from those who dropped out.

PMID- 16466191
TI  - An examination of the research and training needs in the field of deaf education.
AB  - THE NATIONAL CENTER on Low-Incidence Disabilities conducted a needs assessment of
      the research and training needs in the field of deaf education. A total of 331
      professionals, parents, administrators, and university faculty responded to the
      survey. Overall, respondents indicated that the number-one priority was to
      educate administrators about services that are appropriate for students who are
      deaf or hard of hearing. The second most important concern was how to work within
      the education system to change it. The third priority was teaching reading
      strategies. Additional priorities are reported for all respondents, as well as
      comparisons among the different respondent groups. Implications of the results
      are presented.

PMID- 16466192
TI  - The experience of story reading: deaf children and hearing mothers' interactions
      at story time.
AB  - THE STUDY EXAMINED scaffolding interactions between deaf children and hearing
      mothers in which story reading was used as a tool to aid in the development of
      narrative comprehension and linguistic reasoning. The dyadic interactions were
      examined from the perspective of the theoretical works of Vygotsky (1934/1962,
      1978, 1929/1981, 1960/1981). The sample group consisted of 7 dyads of hearing
      mothers and their deaf children ages 4.2 to 9.5 years. The mothers signed a story
      to their children. The dyadic interactions reflected the different levels of
      scaffolding and functioning within the zone of proximal development (Vygotsky,
      1934/1962, 1978). The researchers found that story reading provides an excellent
      framework for both cognitive and emotional growth within the parent/child dyad.
      Mothers who engaged their children in mutual dialogue also used elaboration. This
      was reflected in their children's linguistic reasoning.

PMID- 16466193
TI  - Reading levels of Spanish deaf students.
AB  - THE READING LEVELS of a population of 93 Spanish deaf students were examined. All
      study participants had prelingual profound hearing loss; their ages ranged from 9
      to 20 years. All were enrolled in compulsory education during 2002-2003 in the
      Canary Islands (Spain). They were evaluated with sentence and text comprehension
      subtests from the Evaluation of Reading Processes of Primary Education Students,
      whose Spanish acronym is PROLEC (Cuetos, Rodriguez, & Ruano, 1996). A
      questionnaire on reading attitude was also used (Espin, 1987). Study results were
      consistent with those of previous research: Deaf students, at the end of their
      primary school education (mean age 13 years), have reading levels similar to or
      lower than the reading levels of hearing students at the onset of primary school
      education (mean age 7 years). These deaf students also have an indifferent
      attitude toward reading.

PMID- 16466194
TI  - Developing a standardized comprehensive health survey for use with deaf adults.
AB  - THERE IS LIMITED INFORMATION on how communication barriers impact on the health
      of deaf individuals. The present article describes the development of a
      standardized interview tool to collect health-related information from deaf
      adults via face-to-face interviews in American Sign Language (ASL). Questions
      were selected largely from existing standardized questionnaires. Key steps in
      standardizing the instrument included the creation of an ASL gloss version of the
      survey and extensive interviewer training. The instrument was pilot-tested and
      revised prior to implementation. There were 139 questions on the final
      instrument. A total of 203 interviews were conducted between November 2002 and
      March 2003. A standardized interview survey administered in ASL proved an
      effective and well-accepted means of collecting health-related information from a
      diverse sample of deaf individuals. Several challenges were encountered
      throughout the process, and the resulting lessons will be useful to future
      research efforts.

PMID- 16466195
TI  - The use of aseptic surgery on rodents used in research.

PMID- 16466196
TI  - Placement of intraperitoneal injections in rats.

PMID- 16466197
TI  - Diagnostic exercise: sloughing of limb extremities in immunocompromised suckling
      mice.

PMID- 16466198
TI  - Euthanasia during life science research in space.

PMID- 16466199
TI  - How to survive a barrier break.

PMID- 16466200
TI  - Comparative quality evaluation of two commercial products and experimental diets
      for laboratory rats.

PMID- 16466201
TI  - Technical management of an owl monkey breeding colony in a research laboratory.

PMID- 16466202
TI  - Copulatory behavior and fertility rate (pregnancy rate) of sexually inexperienced
      and experienced male Syrian hamsters.

PMID- 16466203
TI  - Ivermectin overdose in a group of laboratory mice.

PMID- 16466204
TI  - Evaluation of detomidine and ketamine-detomidine for anesthesia in laboratory
      rats.

PMID- 16466205
TI  - Intraocular pressure measurement in non-anesthetized rats by Tono-Pen II
      applanation tonometry.

PMID- 16466206
TI  - Comparative effects of forced-air, individual cage ventilation or an absorbent
      bedding additive on mouse isolator cage microenvironment.

PMID- 16466207
TI  - An inexpensive method for control of methyl-methacrylate fumes in the laboratory.

PMID- 16466208
TI  - Is there a place for quality in higher education?

PMID- 16466209
TI  - Performance evaluation.

PMID- 16466210
TI  - A centralized transgenic core facility within a laboratory animal resources
      program.

PMID- 16466211
TI  - Sample sizes and frequency of testing for health monitoring in barrier rooms and
      isolators.

PMID- 16466212
TI  - An improved small animal restraint for vector-borne disease research.

PMID- 16466213
TI  - Comparative study on the effects of isoflurane, isoflurane with nitrous oxide,
      and thiamylal on percent myocardial infarct and percent area at risk in acute and
      chronic pigs.

PMID- 16466214
TI  - Management, challenged employees, and the ADA.

PMID- 16466215
TI  - Preparation for membership in the American College of Laboratory Animal Medicine.

PMID- 16466217
TI  - The Guinea pig heart--some comparative aspects.

PMID- 16466218
TI  - A practical delivery method for oral administration of ivermectin to large
      colonies of rodents.

PMID- 16466216
TI  - Reference serum revisited.

PMID- 16466219
TI  - The use of foraging devices for environmental enrichment of individually housed
      rhesus monkeys in a laboratory colony.

PMID- 16466220
TI  - A simple and effective environmental enrichment device for ponies in long-term
      indoor confinement.

PMID- 16466222
TI  - A mobile work station incorporating air extract and filtration.

PMID- 16466221
TI  - Effect of population size on humidity and ammonia levels in individually
      ventilated microisolation rodent caging.

PMID- 16466223
TI  - A safe and effective method for repeated rectal temperature measurements in mice.

PMID- 16466224
TI  - Treatment of a fractured phalanx in a Yucatan minipig.

PMID- 16466225
TI  - The past is prologue: a history of the American Association for Laboratory Animal
      Science.

PMID- 16466227
TI  - A vacuum-assisted technique for collection of blood from the Guinea pig.

PMID- 16466228
TI  - Effect of intracage ventilation and automatic watering on outbred mouse
      reproductive performance and weanling growth.

PMID- 16466226
TI  - Design and implementation of a primate foraging tray.

PMID- 16466229
TI  - Thermal sanitization of stainless steel and CPVC watering manifolds.

PMID- 16466230
TI  - A review of the role of temperature time in an effective cage sanitization
      program.

PMID- 16466231
TI  - Eradication programs for pasteurellosis in rabbitries.

PMID- 16466232
TI  - Research animal management problems as a strategy for education and training.

PMID- 16466233
TI  - Epidemiology and natural history of arteriovenous malformations.
AB  - The epidemiology and natural history of cerebral arteriovenous malformations
      (AVMs) remains incompletely elucidated. Several factors are responsible. With
      regard to the incidence and prevalence of AVMs, the results of prior studies have
      suffered because of the retrospective design, the use of nonspecific ICD-9 codes,
      and a focus on small genetically isolated populations. Recent data from the New
      York Islands AVM Hemorrhage Study, an ongoing, prospective, population-based
      survey determining the incidence of AVM-related hemorrhage and the associated
      rates of morbidity and mortality in a zip code-defined population of 10 million
      people, suggests that the AVM detection rate is 1.21/100,000 person-years (95%
      confidence interval [CI] 1.02-1.42) and the incidence of AVM-hemorrhage is
      0.42/100,000 person-years (95% CI 0.32-0.55). Contemporaneous data from the
      Northern Manhattan Stroke Study, a prospective, longitudinal population-based
      study of nearly 150,000 patients in which the focus is to define the incidence of
      stroke, suggest the crude incidence for first-ever AVM-related hemorrhage to be
      0.55/100,000 person-years (95% CI 0.11-1.61). Efforts are ongoing to study the
      natural history of both ruptured and unruptured AVMs in these datasets to examine
      the relevance of prior studies of patients selected for conservative follow up in
      Finland. In addition, data are being gathered to determine whether risk factors
      for future hemorrhage, which have previously been established in small case
      series, are valid when applied to whole populations. Together, these data should
      help inform therapeutic decisionmaking.

PMID- 16466234
TI  - Functional evaluation of arteriovenous malformations.
AB  - Detailed knowledge of the angioarchitecture of arteriovenous malformations (AVMs)
      is necessary in determining the optimal timing and method of treatment of these
      challenging lesions. Many techniques are available for studying the functionality
      of surrounding cortical structures of AVMs. These include the use of positron
      emission tomography, functional magnetic resonance imaging,
      magnetoencephalography, and direct provocative testing of cortical function. The
      use of these methods to determine flow dynamics and tissue perfusion is also
      reviewed. These techniques are discussed in the present study, and their
      judicious utilization will enhance the safety of AVM therapy.

PMID- 16466235
TI  - Grading and surgical planning for intracranial arteriovenous malformations.
AB  - The treatment of arteriovenous malformations (AVMs) has evolved over the last 40
      years. These complex vascular lesions remain among the most difficult lesions to
      treat. Successful treatment of AVMs of the brain includes extensive preoperative
      planning, multimodality treatment options, and modern postoperative surgical
      care. The advent of new technologies, including interventional neuroradiology and
      radiosurgery, has expanded the range of malformations that can be treated
      effectively and has had a significant impact on those individuals who manifest
      this disease process. The purpose of this paper is to describe the current
      grading technique used by the authors and to explore the preoperative treatment
      and planning that leads to successful surgical obliteration of these lesions.
      Some description of preoperative interventions, including radiosurgery and
      interventional procedures will be mentioned; however, only in the context of how
      they impact on the surgical treatment of these lesions. In other articles in this
      edition of Neurosurgical Focus interventional procedures and radiosurgery as
      treatment adjuncts and as primary therapies will be discussed in greater detail.

PMID- 16466236
TI  - Neuropsychological function and brain arteriovenous malformations: redefining
      eloquence as a risk for treatment.
AB  - Arteriovenous malformations (AVMs) of the brain, thought to begin during fetal
      development and undergo an unclear maturation process; most often do not become
      symptomatic until the patient reaches adulthood. Authors of recent prospective
      studies have suggested that relatively few patients present with
      neuropsychological abnormalities in the absence of hemorrhage. In general,
      neuropsychological evaluations in patients with AVMs have yielded mixed results
      with respect to localization of function, and the authors of most cognitive
      studies have not been able to demonstrate the nature and degree of impairment
      seen in acute ischemic stroke in comparable brain regions. Superselective Wada
      testing prior to therapeutic embolization, functional imaging studies, and
      intrasurgical cortical mapping have shown redistribution of language and memory
      to unpredictable regions. Developmental cognitive history in these patients
      indicates that most will have at least some background of learning problems
      during the school-age years with varying degrees of severity, reflecting a time
      when brain reorganization may be occurring. These data suggest that traditional
      assumptions about the eloquence of brain regions may not hold for patients with
      AVMs and that establishing treatment risk in the individual patient needs to be
      made on an empirical basis.

PMID- 16466237
TI  - Anesthesia-related considerations for cerebral arteriovenous malformations.
AB  - In the optimum anesthetic management of patients with cerebral arteriovenous
      malformations (AVMs), the anesthesiologist should be familiar with the general
      pathophysiology of these lesions and various strategies for treatment. In this
      review, the authors outline these issues with special attention to cerebral
      hemodynamic changes induced by AVMs and their resection.

PMID- 16466238
TI  - Preoperative silk suture embolization of cerebral and dural arteriovenous
      malformations.
AB  - OBJECT: The aim of this study was to evaluate the use of silk sutures as a
      medical implant when applied for the embolization of cerebral and dural
      arteriovenous malformations (AVMs). The facility of surgery and the clinical
      significance of complications related to preoperative silk suture embolization
      were evaluated immediately after surgery and at long-term follow up. METHODS:
      Thirty-four patients harboring 29 cerebral and five dural AVMs underwent
      embolization in which silk alone or in association with other agents was used.
      Medical and radiological records obtained in these 34 patients were reviewed
      retrospectively. The cerebral AVMs were classified according to the Spetzler
      Martin grading system and the dural AVMs to the Djindjian grading system. The
      facility of the resection and the adverse outcomes, including new neurological
      deficits, hemorrhage, and fever, as well as histopathological evidence of vessel
      inflammatory changes, were determined in each case. In all 23 surgical cases, the
      AVM could be easily manipulated and excised. New temporary neurological deficits
      occurred in three patients. A high Spetzler-Martin grade was not associated with
      a higher incidence of new neurological deficits. One delayed-onset hemorrhage was
      detected after embolization. Fever was present in 24% of the patients. No sign of
      significant vasculitis or perivascular inflammation was found on radiological or
      histopathological examination. CONCLUSIONS: Silk sutures are safe embolic agents
      especially for proximal occlusion of AVM feeding vessels. New permanent
      neurological deficits were not encountered in this series. Fever was considered
      to be a minor, temporary side effect of silk suture embolization.

PMID- 16466239
TI  - Decision analysis for small, asymptomatic intracranial arteriovenous
      malformations.
AB  - OBJECT: Asymptomatic intracranial arteriovenous malformations (AVMs) represent a
      clinically challenging problem because of the complex decision making that must
      be undertaken prior to beginning any type of treatment. In addition, the relative
      infrequency of these lesions means that there is relatively little experience
      reported in the literature. The authors use a decision-analysis technique to
      model the considerations that go into determining the treatment of these lesions
      in an effort to quantify the various risks and overall benefits conferred by the
      following three treatment strategies: observation/natural history, microsurgery,
      and stereotactic radiosurgery. METHODS: The authors conducted a thorough
      literature search to elucidate the risks and outcomes associated with each
      treatment option. These values were used to build and run a comprehensive Markov
      model to determine a base-case analysis. All of the input variables were also
      subjected to sensitivity analysis to identify the most influential input
      variables and the crossover points in which favored strategies changed. The base
      case analysis suggested that microsurgery was the favored treatment option
      because this hypothetical cohort accumulated 21.53 quality-adjusted life years
      (QALYs) over the course of the model compared with the 16.97 QALYs and 16.40
      QALYs for stereotctic radiosurgery and observation, respectively. Sensitivity
      analysis demonstrated that overall major neurological morbidity and mortality
      were the most influential input variables both perioperatively and during the
      radiosurgical "latent" period (that is, up to 2 years posttreatment). The maximum
      acceptable perioperative combined major neurological morbidity and mortality rate
      was 6.8%. The latent period combined major neurological morbidity and mortality
      would need to be 0.7% to make radiosurgery favorable in this analysis.
      CONCLUSIONS: Results of this decision analysis model suggest that microsurgery in
      the hands of experienced cerebrovascular surgeons, who can expect a less than
      6.8% combined rate of major neurological morbidity and mortality, offers patients
      a greater overall quality of life over time.

PMID- 16466241
TI  - Systematic behavior of charge-transfer transitions and energy level variation in
      soft donor complexes of the trivalent lanthanides.
AB  - The systematic behavior of the charge-transfer (CT) energies in mixed 2,2'
      bipyridyl (bipy), N,N-diethyldithiocarbamate (Et2dtc-) complexes of the trivalent
      lanthanides, Ln(Et2dtc)3(bipy), is investigated to understand the electronic
      structure of f-element complexes containing soft donor ligands. The energies of
      ligand to Ln3+ CT are extremely low in this system, an effect attributed to the
      presence of the soft donor ligands. The lowest CT energy level for the Sm3+,
      Eu3+, and Yb3+ complexes falls into the visible range. In Eu(Et2dtc)(bipy), the
      Eu3+ ion becomes nonluminescent because the CT energy stretches below the
      metastable 5D0 electronic state, whereas luminescence from the CT state and the
      4f13 (2)F(5/2) state are observed in the Yb compound. The variation in the energy
      of the lowest level CT transition for the entire Ln(Et2dtc)3(bipy) series has
      been evaluated using the experimentally determined CT levels of the Sm3+, Eu3+,
      and Yb3+ compounds based on the systematic behavior of the lanthanides, which is
      invariant with respect to the type of ligand. The energy difference between the
      ground electronic states of the lanthanide ions and the ligand-centered valence
      band may also be calculated from these results.

PMID- 16466240
TI  - Postoperative radicular neuroma. Case report.
AB  - Lumbar discectomy is the most common surgical procedure performed in neurosurgery
      clinics. Such a large number of procedures underscore not only the prevalence of
      conditions such as intervertebral disc herniation, but also the strong belief of
      surgeons that the operation does provide benefits to patients suffering from
      sciatica. In spite of this belief, sciatic pain may continue after the surgery.
      The recurrence of sciatic and/or back pain after primary discectomy is called the
      "failed back surgery syndrome." The rate of the complications involved in
      standard lumbar discectomy ranges from 5.4 to 14%. One of the complications of
      the lumbar disc surgery is nerve root injury. The complication rate of this
      injury ranges from 0.7 to 2.2%. Postoperative radicular neuroma must be
      considered in differential diagnosis for the patient who has failed back surgery
      syndrome. In this study the authors evaluate a patient who had undergone surgery
      for lumbar disc herniation and suffered intractable pain. A traumatic radicular
      neuroma is demonstrated and the pertinent literature is presented.

PMID- 16466242
TI  - Novel ground- and excited-state prototropic reactivity of a
      hydroxycarboxyflavylium salt.
AB  - Synthetic and natural hydroxyflavylium salts are super-photoacids, exhibiting
      values of the rate constant for proton transfer to water in the excited state as
      high as 1.5 x 10(11) s(-1). The synthetic flavylium salt 4-carboxy-7-hydroxy-4'
      methoxyflavylium chloride (CHMF) has an additional carboxyl group at the 4
      position of the flavylium cation that deprotonates in the ground state at a lower
      pH (pK(a1) = 0.73; AH2+ --> Z) than the 7-hydroxy group (pK(a2) = 4.84; Z --> A
      ). Ground-state deprotonation of the carboxyl group of the acid (AH2+) to form
      the zwitterion (Z) is too fast to be detected by nanosecond laser flash
      perturbation of the ground-state equilibrium, while deprotonation of the hydroxyl
      group of Z to form the anionic base (A-) occurs in the microsecond time range
      (k(d2) = 0.6 x 10(6) s(-1) and k(p2) = 4.2 x 10(10) M(-1) x s(-1)). In the
      excited state, the cationic form (AH2+) deprotonates in approximately 9 ps,
      resulting in the excited neutral base form (AH), which is unstable in the ground
      state. Deprotonation of Z occurs in 30 ps (k(d2) = 2.9 x 10(10) s(-1)), to form
      excited A-, which either reprotonates (k(p3)* = 3.7 x 10(10) M(-1) x s(-1)) or
      decays in 149 ps, and shows an important contribution from geminate recombination
      to give the excited neutral base (AH). Predominant reprotonation of A- at the
      carboxylate group reflects both the presence of the negative charge on the
      carboxylate and the increase in the excited-state pK(a) of the carboxyl group.
      Thus, while the hydroxyl pK(a) decreases by approximately 5 units upon going from
      the ground state (pK(a) = 4.84) to the excited state (pK(a) = -0.2), that of the
      carboxyl group increases by at least this much. Consequently, the excited state
      of the Z form of CHMF acts as a molecular proton transporter in the picosecond
      time range.

PMID- 16466243
TI  - Amorphous solid water films: transport and guest-host interactions with CO2 and
      N2O dopants.
AB  - Guest-host interactions have been examined experimentally for amorphous solid
      water (ASW) films doped with CO2 or N2O. The main diagnostics are Fourier
      transform infrared (FTIR) spectroscopy and temperature programmed desorption
      (TPD). ASW films deposited at 90 K are exposed to a dopant, and the first
      molecules that attach to a film enter its bulk until it is saturated with them.
      Subsequent dopant adsorption results in crystal growth atop the ASW film. There
      are distinct spectral signatures for these two cases: LO and TO vibrational modes
      for the crystal overlayer, and an easily distinguished peak for dopant molecules
      that reside within the ASW film. Above 105 K, the dopant surface layer desorbs
      fully. Some dopants residing within the ASW film remain until 155 K, at which
      point the ASW-to-crystalline-ice transition occurs, expelling essentially all of
      the dopant. No substantial differences are observed for CO2 versus N2O. It is
      shown that annealing an ASW film to 130 K lowers the film's capacity to include
      dopants by a factor of approximately 3, despite the fact that the ASW spectral
      feature centered at approximately 3250 cm(-1) shows no discernible change.
      Sandwiches were prepared: ASW-dopant-ASW etc., with the dopant layer displaying
      crystallinity. Raising these samples past 105 K resulted in the expulsion of
      essentially all of the crystalline dopant. What remained displayed the same
      spectral signature as the molecules that entered the bulk following adsorption at
      the surface. It is concluded that the adsorption sites, though prepared
      differently, have a lot in common. Dangling OH bonds were observed. When they
      interacted with a dopant, they underwent a red shift of approximately 50 cm(-1).
      This is in qualitative agreement with studies that have been carried out with
      weakly bound binary complexes. As a result of this study, a fairly complete,
      albeit qualitative, picture is in place for the adsorption, binding, and
      transport of CO2 and N2O in ASW films.

PMID- 16466244
TI  - Thermal vaporization of biological nanoparticles: fragment-free vacuum
      ultraviolet photoionization mass spectra of tryptophan, phenylalanine-glycine
      glycine, and beta-carotene.
AB  - A simple, new way to introduce fragile biomolecules into the gas phase via
      thermal vaporization of nanoparticles is described. The general utility of this
      technique for the study of biomolecules is demonstrated by coupling this source
      to tunable synchrotron vacuum ultraviolet radiation. Fragment-free
      photoionization mass spectra of tryptophan, phenylalanine-glycine-glycine, and
      beta-carotene are detected with signal-to-noise ratios exceeding 100. The 8.0 eV
      photoionization mass spectrum of tryptophan nanoparticles vaporized at 373 K is
      dominated by a single parent ion peak that exhibits a 20-fold enhancement over
      the methylene indole fragment ion. The degree of dissociative photoionization of
      tryptophan can be precisely controlled either by the thermal energy imparted into
      the neutral tryptophan molecule or by the energy of the ionizing photon. The
      results reveal how approximately 0.5 eV changes in internal energy affect both
      the photoionization mass spectrum of tryptophan and the appearance energy of the
      daughter ion fragments. This method allows the ionization energies of glycine
      (9.3 +/- 0.1 eV), tryptophan (7.3 +/- 0.2 eV), phenylalanine (8.6 +/- 0.1 eV),
      phenylalanine-glycine-glycine (9.1 +/- 0.1 eV), and beta-carotene (<7.0 eV)
      molecules to be determined directly from the photoionization efficiency spectra.

PMID- 16466245
TI  - Cavity ring-down spectroscopy of the torsional motions of 1,4
      bis(phenylethynyl)benzene.
AB  - The torsional motions of jet-cooled 1,4-bis(phenylethynyl)benzene (BPEB), a
      prototype molecular wire, were studied using cavity ring-down spectroscopy in the
      first UV absorption band (316-321 nm). The torsional spectrum of 1,4
      bis(phenylethynyl)-2,3,5,6-tetradeuteriobenzene was also recorded in the gas
      phase. Both spectra were successfully simulated using simple cosine potentials to
      describe the torsional motions. The ground-state barrier to rotation was
      estimated to be 220-235 cm(-1), which is similar to that of diphenylacetylene
      (tolane). Complementary DFT calculations were found to overestimate the torsional
      barrier.

PMID- 16466246
TI  - Analysis of vibrational circular dichroism spectra of (s)-(+)-2-butanol by
      rotational strengths expressed in local symmetry coordinates.
AB  - The vibrational circular dichroism (VCD) spectra of (S)-(+)-2-butanol have been
      observed in dilute CS(2) solutions. Two strong VCD bands are assigned mainly to
      the OH bending modes with the aid of quantum chemical calculations. The
      calculated VCD spectra corresponding to these bands are shown to depend on the
      conformation of the OH group. To understand this feature, we have calculated the
      contribution of each local vibrational mode to the rotational strengths and
      concluded that the coupling of the group vibrations between the in-plane and out
      of-plane modes about the locally assumed symmetry planes play a significant role
      in VCD. This finding has provided a new scope of VCD in relation to molecular
      vibrations.

PMID- 16466247
TI  - Vibronic structure of jet-cooled 2,6-dimethylbenzyl radical: revisited.
AB  - We reexamined the vibronic structure of the jet-cooled 2,6-dimethylbenzyl radical
      that was generated from 1,2,3-trimethylbenzene seeded in a large amount of inert
      carrier gas helium using a pinhole-type glass nozzle in a corona excited
      supersonic expansion, from which the vibronically resolved emission spectrum was
      recorded with a long path double monochromator in the visible region. The
      spectrum exhibited bands arising from not only the D1 --> D0 transition but also
      the D2 --> D0 transition, in which transitions the accurate electronic energies
      of the D2 and D1 states and the revised vibrational mode frequencies in the
      ground electronic state were obtained by comparison with those from the known
      data of the precursor and an ab initio calculation.

PMID- 16466248
TI  - Spectroscopic and quantum chemical study of the novel compound
      cyclopropylmethylselenol.
AB  - An investigation into the properties of the novel compound
      cyclopropylmethylselenol has been undertaken by use of Stark-modulation microwave
      spectroscopy and high-level quantum chemical calculations. Ground-state spectra
      belonging to six isotopomers of a single conformer of the molecule were recorded
      and assigned. This conformer, predicted to be the lowest in energy by a series of
      quantum chemical calculations, possesses a synclinal arrangement of the H-C-C-Se
      atoms. In addition to the assignment of these ground-state spectra, transitions
      attributable to vibrationally excited states of the 78Se- and 80Se-containing
      isotopomers were identified. A tentative assignment of these excited-state
      spectra to specific vibrational modes has been made with the assistance of a
      density functional theory calculation at the B3LYP/6-311++G(3df,2pd) level of
      theory. Close agreement was found between experimental ground-state rotational
      constants and ab initio equilibrium values calculated at the MP2/aug-cc-pVTZ
      level of theory. Good agreement was also noted between certain r(s) principal
      axis coordinates of atoms in the molecule and the corresponding ab initio r(e)
      values. Limited evidence in favor of the formation of a weak intramolecular
      hydrogen bond between the H atom of the selenol group and electron density
      associated with the cyclopropyl ring is discussed.

PMID- 16466249
TI  - Conformation and intramolecular hydrogen bonding of 2-chloroacetamide as studied
      by microwave spectroscopy and quantum chemical calculations.
AB  - The microwave spectrum of 2-chloroacetamide (ClCH2CONH2) has been investigated at
      room temperature in the 19-80 spectral range. Spectra of the 35ClCH2CONH2 and
      37ClCH2CONH2 isotopomers of one conformer, which has a symmetry plane (Cs
      symmetry), were assigned. The amide group is planar, and an intramolecular
      hydrogen bond is formed between the chlorine atom and the nearest hydrogen atom
      of the amide group. The ground vibrational state, six vibrationally excited
      states of the torsional vibration about the CC bond, as well as the first excited
      state of the lowest bending mode were assigned for the 35ClCH2CONH2 isotopomer,
      whereas the ground vibrational state of 37ClCH2CONH2 was assigned. The CC
      torsional fundamental vibration has a frequency of 62(10) cm(-1), and the bending
      vibration has a frequency of 204(30) cm(-1). The rotational constants of the
      ground and of the six excited states of the CC torsion were fitted to the
      potential function Vz = 16.1(<z4> + 2.3<z2>) cm(-1), where z is a dimensionless
      parameter. This function indicates that the equilibrium conformation has Cs
      symmetry. Rough values of the chlorine nuclear quadrupole coupling constants were
      derived as chi(aa) = -47.62(52) and chi(bb) = 8.22(66) MHz for the 35Cl nucleus
      and chi(aa) = -34.6(10) and chi(bb) = 6.2(11) MHz for the 37Cl nucleus. Ab initio
      and density functional theory quantum chemical calculations have been performed
      at several levels of theory to evaluate the equilibrium geometry of this
      compound. The density functional theory calculations at the B3LYP/6
      311++G(3df,2pd) and B3LYP/cc-pVTZ levels of theory as well as ab initio
      calculations at the MP2(F)/cc-pVTZ level predict correct lowest-energy
      conformation for the molecule, whereas the ab initio calculations at the
      QCISD(FC)/6-311G(d) and MP2(F)/6-311++G(d,p) levels predict an incorrect
      equilibrium conformation.

PMID- 16466250
TI  - Q-band EPR and ENDOR of low temperature X-irradiated beta-D-fructose single
      crystals.
AB  - Beta-D-fructose single crystals were in situ X-irradiated at 80 K and measured
      using electron paramagnetic resonance (EPR), electron nuclear double resonance
      (ENDOR) and ENDOR-induced EPR (EIE) techniques at Q-band (34 GHz) microwave
      frequencies. The measurements revealed the presence of at least four carbon
      centered radicals stable at 80 K. By means of ENDOR angular variations in the
      three principal crystallographic planes, six proton hyperfine coupling tensors
      could be determined and were assigned to four different radicals by the aid of
      EIE. Two of the radicals exhibit only beta-proton hyperfine couplings and reveal
      almost identical EIE spectra. For the other two radicals, the major hyperfine
      splitting originates from a single alpha-proton hyperfine coupling and their EIE
      spectra were also quite similar. The similarity of the EIE spectra and hyperfine
      tensors led to the assumption that there are only two essentially different
      radical structures. The radical exhibiting only beta-proton hyperfine couplings
      was assigned to a C3 centered radical arising from H3 abstraction and the other
      radical suggested to be an open-ring species with a disrupted C2-C3 bond and a
      double C2-O2 bond. A possible formation mechanism for the latter open-ring
      radical is presented. By means of cluster density functional theory (DFT)
      calculations, the structures of the two radicals were determined and a fairly
      good agreement between the calculated and experimental hyperfine tensors was
      found.

PMID- 16466251
TI  - Reactivity of small Mo(x)Oy- clusters toward methane and ethane.
AB  - The reactions of Mo2Oy- suboxide clusters with both methane and ethane have been
      studied with a combination of mass spectrometry, anion photoelectron
      spectroscopy, and density functional theory calculations. Reactions were carried
      out under "gentle" and "violent" conditions. For methane, a number of products
      appeared under the gentler source conditions that were more logically attributed
      to dissociation of Mo2Oy- clusters upon reacting with methane to form MoCH2-,
      Mo(O)CH2-, and HMo(O2)CH3-. With ethane, products observed under the same gentle
      conditions were Mo(O)C2H2-, Mo(O)C2H4-, Mo(O2)C2H4-, and Mo(O2)(C2H5)2-. As
      expected, more products were observed when the reactions were carried out under
      violent conditions. The photoelectron spectra obtained for these species were
      compared to calculated adiabatic and vertical electron affinities and vibrational
      frequencies, leading to definitive structural assignments for several of the
      products.

PMID- 16466252
TI  - An optimized semidetailed submechanism of benzene formation from propargyl
      recombination.
AB  - The self-reaction of propargyl (C3H3) radicals has been widely suggested as one
      of the key routes forming benzene in a variety of aliphatic flames. Currently, in
      the majority of aromatic models, the C3H3 + C3H3 submechanism often contains one
      or two C6H6 isomers and a few global reaction steps, which do not adequately
      represent the actual recombination chemistry. Recent experimental and theoretical
      studies on the direct propargyl recombination and subsequent C6H6 isomerization
      have provided sufficient information to revisit and revise the C3H3 + C3H3
      reaction submechanism. In the present work, a semidetailed kinetic model
      consisting of seven isomeric C6H6 species and 14 reaction steps was constructed
      based on the most recent potential energy surface for this system. The trial
      model was subjected to systemic optimization by use of a recently developed
      physically bounded Gauss-Newton (PGN) method against detailed species profiles of
      direct propargyl recombination and 1,5-hexadiyne (15HD) isomerization obtained
      from experiments at high temperatures in a shock tube and at low temperatures in
      a flow reactor, which were all measured at very high pressure (shock tube) or
      atmospheric (flow reactor) conditions. Predictions of the optimized model were in
      excellent agreement with all experimental measurements. The optimized C3H3 + C3H3
      reaction subset was also tested for flame modeling. Two different aromatic
      chemistry models that incorporate benzene formation from propargyl radicals as a
      single step reaction were modified to include the complete submechanism for
      propargyl recombination. The updated models predict significant percentages of
      three isomeric species [2-ethynyl-1,3-butadiene (2E13BD), fulvene, and benzene]
      in premixed fuel-rich acetylene and ethylene flames, reflecting the observed
      flame structures.

PMID- 16466253
TI  - Free radical chemistry of disinfection-byproducts. 1. Kinetics of hydrated
      electron and hydroxyl radical reactions with halonitromethanes in water.
AB  - Halonitromethanes are disinfection-byproducts formed during ozonation and
      chlorine/chloramine treatment of waters that contain bromide ion and natural
      organic matter. In this study, the chemical kinetics of the free-radical-induced
      degradations of a series of halonitromethanes were determined. Absolute rate
      constants for hydroxyl radical, *OH, and hydrated electron, e(aq)-, reaction with
      both chlorinated and brominated halonitromethanes were measured using the
      techniques of electron pulse radiolysis and transient absorption spectroscopy.
      The bimolecular rate constants obtained, k (M(-1) s(-1)), for e(aq)-/*OH,
      respectively, were the following: chloronitromethane (3.01 +/- 0.40) x
      10(10)/(1.94 +/- 0.32) x 10(8); dichloronitromethane (3.21 +/- 0.17) x
      10(10)/(5.12 +/- 0.77) x 10(8); bromonitromethane (3.13 +/- 0.06) x 10(10)/(8.36
      +/- 0.57) x 10(7); dibromonitromethane (3.07 +/- 0.40) x 10(10)/(4.75 +/- 0.98) x
      10(8); tribromonitromethane (2.29 +/- 0.39) x 10(10)/(3.25 +/- 0.67) x 10(8);
      bromochloronitromethane (2.93 +/- 0.47) x 10(10)/(4.2 +/- 1.1) x 10(8);
      bromodichloronitromethane (2.68 +/- 0.13) x 10(10)/(1.02 +/- 0.15) x 10(8); and
      dibromochloronitromethane (2.95 +/- 0.43) x 10(10) / (1.80 +/- 0.31) x 10(8) at
      room temperature and pH approximately 7. Comparison data were also obtained for
      hydroxyl radical reaction with bromoform (1.50 +/- 0.05) x 10(8),
      bromodichloromethane (7.11 +/- 0.26) x 10(7), and chlorodibromomethane (8.31 +/-
      0.25) x 10(7) M(-1) s(-1), respectively. These rate constants are compared to
      recently obtained data for trichloronitromethane and bromonitromethane, as well
      as to other established literature data for analogous compounds.

PMID- 16466254
TI  - Chemoselectivities in acetalization, thioacetalization, oxathioacetalization and
      azathioacetalization.
AB  - In the present article (experimental as well theoretical) the relative yields of
      cyclic (O,O), (S,S), (S,O), and (S,N) acetals, formed from p-(NO2)C6H4CHO and p
      (OH)C6H4CHO, are compared. Atomic charges, global electrophilicity descriptor (w)
      [as proposed by Parr et al., J. Am. Chem. Soc. 1999, 121, 1922] and hard-soft
      acid-base concept of Pearson (J. Am. Chem. Soc. 1963, 85, 3533) are used to
      explain the experimental observations. Although the w values can explain the
      yields, charge and local softness values of the interacting sites explain the
      plausible reaction mechanism. The bisnucleophiles chosen for acetalization are
      CH2(OH)-CH2(OH) (glycol), CH2(SH)-CH2(SH) (dithiol), CH2(OH)-CH2(SH) (oxathiol)
      and CH2(SH)-CH2(NH2) (azathiol). For p-(NO2)C6H4CHO, the experimental yield of
      cyclic acetals were found to follow the trend as (S,N) > (S,O) > (O,O) > (S,S),
      which is also supported by theoretical explanation based on the w values and
      applying the concept of hard-hard (i.e., charge-controlled) and soft-soft (i.e.,
      orbital-controlled) interaction between the interacting sites of the substrates
      (i.e., aldehydes) and the reactants (bisnucleophiles). Similarly, for p
      (OH)C6H4CHO the relative yields of cyclic acetals follow the trend (S,N)
      approximately (S,S) > (S,O) > (O,O). It is argued that the attack on C(CHO)
      (i.e., C-atom of the CHO group) in p-(NO2)C6H4CHO by O(OH) (i.e., O-atom of OH
      group) or N(NH2) (i.e., N-atom of NH2 group) is mainly charge-controlled but the
      attack on C(CHO) in p-(OH)C6H4CHO) by S(SH) (i.e., S-atom of SH group) is orbital
      controlled.

PMID- 16466256
TI  - Mechanistic insights into NO3* induced self-terminating radical oxygenations,
      part 1: a computational study on NO3* and its addition to alkynes.
AB  - The geometry of the nitrate radical, NO3*, for which unrestricted Hartree-Fock
      (HF) breaks spatial symmetry of the wave function, was optimized using hybrid
      density functionals that include varying fractions of Hartree-Fock exchange.
      Although symmetry breaking was not observed even when the functional with the
      highest HF exchange (BHandHLYP) was used, only B3LYP correctly describes the
      D(3h) symmetry of NO3* as ground-state structure with the lowest energy. Further,
      geometries and energies of the stationary points in the addition of NO3* to
      ethyne, propyne, and 2-butyne were calculated using ab initio and density
      functional methods. The reactions proceed through Z-configurated transition
      states leading to Z-configurated vinyl radicals with the activation barrier
      decreasing with increasing methyl substitution at the C[triple bond]C by ca. 11
      kJ mol(-1) per methyl group. It was found that the results obtained at the
      BHandHLYP/cc-pVDZ level of theory are in good agreement with the data from single
      point QCISD and CCSD(T) calculations.

PMID- 16466257
TI  - Explicit solvent DRF INDOs/CIS computations of charge transfer state energetics
      in a pyrenyldeoxyuridine nucleoside model.
AB  - In this work we present calculated absorption and emission spectra in
      acetonitrile (MeCN) solution of N-acetyl-1-aminopyrene (PAAc, a spectroscopic
      model compound) and N-(1-pyrenyl)-1-methyluracil-5-carboxamide (PAU(Me), a
      computational model for 5-(N-carboxyl-1-aminopyrenyl)-2'-deoxyuridine (PAdU)).
      The computational method used--the discrete reaction field approach (DRF)-
      combines a quantum mechanical (QM) description of the solute (here DFT and
      INDOs/CIS, i.e., the INDO parametrization for spectroscopy) with a classical,
      molecular mechanics (MM) description of the solvent molecules. The latter are
      modeled with point charges representing the permanent charge distribution and
      polarizabilities to account for many-body interactions among the solute and other
      solvent molecules. Molecular dynamics is used to sample the degrees of freedom of
      the solution around several solute conformations each in two electronic excited
      states. This leads to a large number of solute/solvent configurations from which
      800 are selected for each excited state and collected into a single ensemble by
      means of proper Boltzmann averaging. DRF INDOs/CIS applied to the selected
      solute/solvent configurations give simulated absorption and emission band spectra
      -each based on 15,200 calculated transitions--that compare well with experimental
      results. For example, the much broader absorption and emission bands in PAdU
      compared with PAAc are reproduced, and the simulated emission spectra of PAU(Me)
      agree well with broad (380-550 nm) charge transfer (CT) emission seen for PAdU in
      MeCN. The observed multiexponential fluorescence decay profiles for PAdU in
      different polar solvents are interpreted in terms of solute/solvent
      conformational heterogeneity here generated in the MD simulations for PAU(Me) in
      MeCN. Additionally, the simulations demonstrate the mixing of the forbidden
      Py*+/dU*- CT states with allowed pyrenyl 1(pi,pi*) states.

PMID- 16466255
TI  - Car-parrinello molecular dynamics simulation of liquid formic acid.
AB  - First-principles molecular dynamics has been used to investigate the structural,
      vibrational, and energetic properties of formic acid, formic acid-formate anion
      dimers, and liquid formic acid in a periodically repeated box with 32 formic acid
      molecules. We found that in liquid formic acid the hydrogen-bonded clusters
      mainly consist of linear branching chains. From our simulation, we got good
      agreement with the available structural and dynamical data. We also studied the
      proton transfer in the cis-formic acid-formate anion dimer, and we showed that
      this proton transfer does not have any potential barrier. The hydrogen bonding
      statistics as well as the mean lifetime of the hydrogen bonds are analyzed.

PMID- 16466258
TI  - Shape persistence and bistability of planar three-fold core polyphenylene
      dendrimers: a molecular dynamics study.
AB  - We present an atomistic molecular dynamics investigation of the structural time
      evolution of isolated polyphenylene dendrimers, carbon based dendrimers with a
      planar core formed by a 1,3,5 trisubstituted benzene ring. Simulations are
      carried out at low (80 K) and room temperature. A general classification of the
      conformations (core conformations) assumed by the three dendrimer branches with
      respect to the planar core is presented. It is found that out of the six possible
      core conformations only four are stable, the remaining two being unstable for
      steric reasons. For second generation dendrimers, two of the four accessible core
      conformations are associated with an open arrangement of the three branches
      attached to the planar 3-fold core of the dendrimer, whereas the remaining two
      are associated with a collapsed arrangement of two branches. At low temperature
      the initial conformation is generally conserved whereas at room temperature jumps
      among the four possible core conformations are observed in the nanosecond time
      range. For second generation dendrimers the core conformation jumps are
      associated with an oscillation between two global shape states: open and
      collapsed. The computed bistability of the global shape suggests additional
      possible functional uses for some of these carbon based dendrimers.

PMID- 16466259
TI  - Cooperative effects and strengths of hydrogen bonds in open-chain cis
      triaziridine clusters (n = 2-8): a DFT investigation.
AB  - We employ DFT/B3LYP method to investigate linear open-chain clusters (n = 2-8) of
      the cis-triaziridine molecule that is a candidate molecule for high energy
      density materials (HEDM). Our calculations indicate that the pervasive phenomena
      of cooperative effects are observed in the clusters of n = 3-8, which are
      reflected in changes in lengths of N...H hydrogen bonds, stretching frequencies,
      and intensities of N-H bonds, dipole moments, and charge transfers as cluster
      size increases. The n(N) --> sigma*(N-H) interactions, i.e., the charge transfers
      from lone pairs (n(N)) of the N atoms into antibonds (sigma*) of the N-H bonds
      acting as H-donors, can be used to explain the observed cooperative phenomena.
      The approaches based upon natural bond orbital (NBO) method and theory of atoms
      in molecule (AIM) to evaluating N...H strengths are found to be equivalent. In
      the process of N...H bonding, cooperative nature of n(N) --> sigma*(N-H)
      interactions promotes formation of stronger N...H bonds as reflected in increases
      in the capacities of cis-triaziridine clusters to concentrate electrons at the
      bond critical points of N...H bonds. The calculated nonadditive energies also
      show that the cooperative effects due to n(N) --> sigma*(N-H) interactions indeed
      provide additional stabilities for the clusters.

PMID- 16466260
TI  - La2@C72 and Sc2@C72: computational characterizations.
AB  - The La2@C72 and Sc2@C72 metallofullerenes have been characterized by systematic
      density functional computations. On the basis of the most stable geometry of 39
      C72 hexaanions and the computed energies of the best endofullerene candidates,
      the experimentally isolated La2@C72 species was assigned the structure coded
      #10611. The good agreement between the computed and the experimental 13C chemical
      shifts for La2@C72 further supports the literature assignment (Kato, H.;
      Taninaka, A.; Sugai, T.; Shinohara, H. J. Am. Chem. Soc. 2003, 125, 7782). The
      geometry, IR vibrational frequencies, and 13C chemical shifts of Sc2@C72 were
      predicted to assist its future experimental characterization.

PMID- 16466261
TI  - Calculation of solvent shifts on electronic g-tensors with the conductor-like
      screening model (COSMO) and its self-consistent generalization to real solvents
      (direct COSMO-RS).
AB  - The conductor-like screening model (COSMO) was used to investigate the solvent
      influence on electronic g-values of organic radicals. The previously studied
      diphenyl nitric oxide and di-tert-butyl nitric oxide radicals were taken as test
      cases. The calculations employed spin-unrestricted density functional theory and
      the BP and B3LYP density functionals. The g-tensors were calculated as mixed
      second derivative properties with respect to the external magnetic field and the
      electron magnetic moment. The first-order response of the Kohn-Sham orbitals with
      respect to the external magnetic field was determined through the coupled
      perturbed DFT approach. The spin-orbit coupling operator was treated using an
      accurate multicenter spin-orbit mean-field (SOMF) approach. Provided that
      important hydrogen bonds are explicitly modeled by a supermolecule approach and
      that the basis set is sufficiently saturated, the COSMO calculations lead to
      accurate predictions of isotropic g-shifts with deviations of not more than 100
      ppm relative to experiment. Very accurate results were obtained by employing a
      recently developed self-consistent modification of the COSMO method to real
      solvents (COSMO-RS), which we briefly introduce in this paper as direct COSMO-RS
      (D-COSMO-RS). This model gives isotropic g-shifts of similar high accuracy for
      water without using the supermolecule approach. This is an important result
      because it solves many of the problems associated with the supermolecule approach
      such as local minima and the choice of a suitable model system. Thus, the self
      consistent D-COSMO-RS incorporates some specific solvation effects into continuum
      models, in particular it appears to successfully model the effects of hydrogen
      bonding. Although not yet widely validated, this opens a novel approach for the
      calculation of properties which so far only could be calculated by the inclusion
      of explicit solvent molecules in continuum solvation methods.

PMID- 16466262
TI  - Alkylation of phenol: a mechanistic view.
AB  - The current work utilizes the ab initio density functional theory (DFT) to
      develop a molecular level of the mechanistic understanding on the phenol
      alkylation in the presence of a cation-exchange resin catalyst, Amberlyst-15. The
      catalyst is modeled with the benzene sulfonic acid, and the effect of this acid
      on olefins such as isopropene (i-Pr) and tributene (t-Bu) in a phenol solution
      mimics the experimental condition. A neutral-pathway mechanism is established to
      account for early-stage high concentration of the phenolic ether observed in
      experiments. The mechanism involves an exothermic reaction between olefin and the
      benzene sulfonic acid to form ester followed by three reaction pathways leading
      to direct O-alkylation, o-C-alkylation, and p-C-alkylation. Our calculations
      conclude that O-alkylation to form the phenolic ether is the most energetically
      favorable in the neutral condition. An ionic rearrangement mechanism describes
      intramolecular migrations of the alkyl group from the phenolic ether to form C
      alkylphenols, while the positively charged protonation significantly lowers
      transition barriers for these migrations. The ionic rearrangement mechanism
      accounts for high yields of o-C-alkylphenol and p-C-alkylphenol. Competition
      between the H atom and the alkyl R group at the substitutive site of the
      protonated ortho configuration is found to be the determining factor to the
      ortho/para ratio of C-alkylation products.

PMID- 16466263
TI  - Preferential solvation of phenol in binary solvent mixtures. A molecular dynamics
      study.
AB  - Molecular dynamics computer simulations were carried out to study the
      preferential solvation of phenol in equimolar acetonitrile-water and ethanol
      water binary mixtures. Two water models were used to investigate the model
      dependence of preferential solvation. The results are compared to recent
      intermolecular 1H NOESY experiments reported on the same systems. In the case of
      acetonitrile-water the local mole fraction obtained from simulations agrees quite
      well with experiments. In the case of ethanol-water there was a qualitative
      difference, which was observed for both water models. However, when comparing the
      degree of preferential solvation of the two cosolvents ethanol and acetonitrile
      with each of the two water models, the trend obtained from the simulations agrees
      with experimental data.

PMID- 16466264
TI  - Chiral recognition in self-complexes of tetrahydroimidazo[4,5-d]imidazole
      derivatives: from dimers to heptamers.
AB  - The chiral discrimination in the self-association of chiral 1,3a,4,6a
      tetrahydroimidazo[4,5-d]imidazoles has been studied using density functional
      theory methods. Clusters from dimers to heptamers have been considered. The
      heterochiral dimers (RR:SS or SS:RR) are more stable than the homochiral ones
      (RR:RR or SS:SS) with energy differences up to 17.5 kJ/mol. Besides, in larger
      clusters the presence of two adjacent homochiral molecules impose an energetic
      penalty when compared to alternated chiral systems (RR:SS:RR:SS...). The
      differences in interaction energy within the dimers of the different derivatives
      have been analyzed based on the atomic energy partition carried out within the
      atoms in molecules framework. The mechanism of proton transfer in the homo- and
      heterochiral dimers shows large transition-state barriers except in those cases
      in which a third additional molecule is involved in the transfer. The optical
      rotatory power of several clusters of the parent compound have been calculated
      and rationalized based on the number of homochiral interactions and the number of
      monomers of each enantiomer within the complexes.

PMID- 16466265
TI  - Structural characterization of the 1-butyl-3-methylimidazolium chloride ion pair
      using ab initio methods.
AB  - Ab initio theoretical methods are used to investigate the gas-phase ion pairs of
      the ionic liquid 1-butyl-3-methylimidazolium chloride. Multiple stable conformers
      with the chloride anion positioned (in-plane) around the imidazolium ring or
      above the C2-H bond are determined. The relative energy ordering of the
      conformers is examined at the B3LYP, MP2, and CCSD(T) levels. Zero-point
      energies, BSSE, and basis set effects are examined. For accurate results,
      correlation (dispersion) effects must be included. The most stable conformers are
      essentially degenerate and have the chloride H-bonding to, or lying above, the C2
      H bond. Other conformers are found to lie approximately 30 and approximately 60
      kJ mol(-1) higher in energy. Results are compared with those from recent
      simulations and experimental studies. The effect of the chloride anion on
      rotation of the butyl chain is investigated and found to lower some rotational
      barriers while enhancing others. The origin of the rotational barriers is
      determined. The number and type of hydrogen bonds formed between the imidazolium
      cation and chloride anion is found to vary significantly among conformers. No
      evidence of a possible intra C(alkyl)-H...pi interaction is obtained; however,
      hints of a Cl...pi interaction are found. The vibrational spectrum of each
      conformer is examined, and the origin of multiple (H-bonding) features in the
      vibrational spectrum of the ionic liquid explained.

PMID- 16466266
TI  - Electronic compressibility and polarizability: origins of a correlation.
AB  - Recently, two new chemical concepts have been introduced, namely, the atomic
      compressibility beta' = r4/Z(eff) and the corresponding group (molecular)
      compressibility Gbeta' = summation(i)N=1n(i)beta'(i). Here, r is the radius of
      the atom, Z(eff) is the effective nuclear charge, n is the number of atoms of a
      given element i, and N is the total number of different elements in the molecule.
      The physical meaning of these two compressibility parameters is examined briefly
      in this work. A fundamental difficulty with the derivation of the primary
      relationship beta' = r4/Z(eff) is pointed out. We have investigated the origins
      of an observed linear variation of Gbeta' with molecular polarizability
      alpha(mol)' for a series of predominantly organic molecules. We show that a
      linear correlation is to be expected for a plot of Gbeta' vs alpha(mol)' if
      certain conditions are satisfied for all members of a given set of molecules. In
      particular, if the average value of r/Z(eff) for the constituent atoms is similar
      for each molecule in the series, then a linear variation is to be expected for
      Gbeta' vs alpha(mol)'.

PMID- 16466267
TI  - Ab initio determination of optical rotatory dispersion in the conformationally
      flexible molecule (R)-epichlorohydrin.
AB  - Ab initio optical rotation data from linear-response coupled-cluster and density
      functional methods are compared to both gas-phase and liquid-phase polarimetry
      data for the small, conformationally flexible molecule epichlorohydrin. Three
      energy minima exist along the C-C-C-Cl dihedral angle, each with strong,
      antagonistic specific rotations ranging from ca. -450 to +500 deg/[dm (g/mL)] at
      355 nm. Density-functional theory (specifically the B3LYP functional)
      consistently overestimates the optical rotations of each conformer relative to
      coupled-cluster theory (in agreement with our earlier observations for
      conformationally rigid species), and we attribute this to density-functional
      theory's underestimation of the lowest-lying excitation energies of
      epichlorohydrin. Length- and velocity-gauge formulations of the coupled-cluster
      response function lead to slightly different specific rotations (ca. 7% at short
      wavelengths). We have determined well-converged Gibbs free energy differences
      among the conformers using complete-basis-set extrapolations of coupled-cluster
      energies including triple excitations to obtain Boltzmann-averaged specific
      rotations for comparison to the gas-phase results. The length-gauge coupled
      cluster data agree remarkably well with experiment, with the velocity-gauge
      coupled-cluster and density-functional data bracketing the experimental results
      from below and above, respectively. Liquid-phase conformer populations reported
      earlier by Polavarapu and co-workers from combined infrared absorption and
      theoretical analyses differ markedly from the gas-phase populations, particularly
      for polar solvents. Nevertheless, Boltzmann-averaged specific rotations from both
      coupled-cluster and density-functional calculations agree well with the
      corresponding experimental intrinsic rotations, although the theoretical specific
      rotations for the individual conformers do not take solvent effects into account.
      PCM-based estimates of conformer populations lead to poor agreement with
      experiment.

PMID- 16466268
TI  - Energetics of the thermal dimerization of acenaphthylene to heptacyclene.
AB  - The energetics of the thermal dimerization of acenaphthylene to give Z- or E
      heptacyclene was investigated. The standard molar enthalpy of the formation of
      monoclinic Z- and E-heptacyclene isomers at 298.15 K was determined as
      Delta(f)H(m)o (E-C24H16, cr) = 269.3 +/- 5.6 kJ x mol(-1) and Delta(f)H(m)o (Z
      C24H16, cr) = 317.7 +/- 5.6 kJ x mol(-1), respectively, by microcombustion
      calorimetry. The corresponding enthalpies of sublimation, Delta(sub)H(m)o (E
      C24H16) = (149.0 +/- 3.1) kJ x mol(-1) and Delta(sub)H(m)o (Z-C24H16) = (128.5 +/
      2.3) kJ x mol(-1) were also obtained by Knudsen effusion and Calvet-drop
      microcalorimetry methods, leading to Delta(f)H(m)o (E-C24H16, g) = (418.3 +/-
      6.4) kJ x mol(-1) and Delta(f)H(m)o (Z-C24H16, g) = (446.2 +/- 6.1) kJ x mol(-1),
      respectively. These results, in conjunction with the reported enthalpies of
      formation of solid and gaseous acenaphthylene, and the entropies of
      acenaphthylene and both hepatcyclene isomers obtained by the B3LYP/6-31G(d,p)
      method led to the conclusion that at 298.15 K the thermal dimerization of
      acenaphthylene is considerably exothermic and exergonic in the solid and gaseous
      states (although more favorable when the E isomer is the product), suggesting
      that the nonobservation of the reaction under these conditions is of kinetic
      nature. A full determination of the molecular and crystal structure of the E
      dimer by X-ray diffraction is reported for the first time. Finally, molecular
      dynamics computer simulations on acenaphthylene and the heptacyclene solids were
      carried out and the results discussed in light of the corresponding structural
      and Delta(sub)H(m)o data experimentally obtained.

PMID- 16466269
TI  - Physical nature of interactions within the active site of cytosine-5
      methyltransferase.
AB  - The physical nature of interactions within the active site of cytosine-5
      methyltransferase (CMT) was studied using a variation-perturbation energy
      decomposition scheme defining a sequence of approximate intermolecular
      interaction energy models. These models have been used to analyze the catalytic
      activity of residues constituting cytosine-5-methyltransferase active site as
      well their role in the binding group of de novo designed inhibitors. Our results
      indicate that Glu119, Arg163, and Arg165 appear to play the dominant role in
      stabilizing the protonated transition state structure and their influence can be
      qualitatively approximated by electrostatic interactions alone. The stabilization
      of neutral structures of the alternative reaction pathway is small, which might
      suggest the protonated pathway as preferred by the enzyme. Exchange and
      delocalization terms are negligible in most cases, or they cancel each other to
      some extent. Interactions of inhibitors with the CMT active site are dominated by
      electrostatic multipole contributions in analogy with previously studied
      transition state analogue inhibitors of leucyl aminopeptidase.

PMID- 16466271
TI  - Should patients have a greater role in valuing health states?
AB  - Currently, health state values are usually obtained from members of the general
      public trying to imagine what the state would be like rather than by patients who
      are actually in the various states of health. Valuations of a health state by
      patients tend to vary from those of the general population, and this seems to be
      due to a range of factors including errors in the descriptive system, adaptation
      to the state and changes in internal standards. The question of whose values are
      used in cost-effectiveness analysis is ultimately a normative one, but the
      decision should be informed by evidence on the reasons for the differences. There
      is a case for obtaining better informed general population preferences by
      providing more information on what it is like for patients (including the process
      of adaptation).

PMID- 16466272
TI  - How to present the business case for healthcare quality to employers.
AB  - Many employers in the US are investing in new programmes to improve the quality
      of medical care and simultaneously shifting more of the healthcare costs to their
      employees without understanding the implications on the amount and type of care
      their employees will receive. These seemingly contradictory actions reflect an
      inability by employers to accurately assess how their health benefit decisions
      affect their profits. This paper proposes a practical method that employers can
      use to determine how much they should invest in the health of their workers and
      to identify the best benefit designs to encourage appropriate healthcare delivery
      and use. This method could also be of value to employers in other countries who
      are considering implementing programmes to improve employee health. The method
      allows a programme that improves workers' health to generate four financial
      benefits for an employer - reduced medical costs, reduced absences, improved on
      the-job productivity, and reduced turnover - and uses accurate estimates of the
      benefits of reducing absences and improving productivity.

PMID- 16466273
TI  - What value health?: A review of health state values used in early technology
      assessments for NICE.
AB  - The objective of this article was to review the methods used to obtain quality-of
      life (utility) weights reported in assessments carried out for the National
      Institute for Health and Clinical Excellence (NICE).The design of the review was
      a cross-sectional survey. Health technology assessment (HTA) reports published on
      the NICE website up to May 2003 were reviewed. Data were extracted on the
      following: the approach to utility estimation (direct or indirect), how health
      states were described for indirect estimation, valuation techniques used
      (standard gamble [SG], time trade-off [TTO], visual analogue scale [VAS], etc.),
      whether uncertainty in utility estimates was explored in cost-utility analyses,
      and whether utility values were identified as a priority for further research by
      assessment authors.Fifty-six assessments were reviewed, of which 28 reported 45
      cost-utility analyses. There was striking variation in the values used to
      describe different health states. Data from patients were used in 15 (33%)
      analyses, from the general public in 10 (22%) and from clinicians in 4 (9%). In
      16 (36%) cases, the source for utility estimates was unclear. Health states were
      described using a range of generic and disease-specific measures, although the EQ
      5D was used most frequently. In 25 analyses (56%), the valuation technique used
      was not reported. TTO was used in 11 (24%), SG in 3 (7%), magnitude estimation in
      5 (11%) and VAS in 1 (2%). Sensitivity analyses based on utility values were
      reported in 25 cases (56%), more commonly in reports of analyses carried out by
      independent teams than technology sponsors although this may be subject to
      reporting bias. Further research into quality of life was recommended in 17 (61%)
      of the 28 assessment reports that contained at least one cost-utility analysis.
      Greater transparency and consistency are required in reporting the methods used
      to obtain quality-of-life weights in cost-utility analyses, and better sources of
      data are required. Methodological variation results in important differences in
      values. Therefore, caution must be exercised when comparing the results of
      different cost-utility analyses.

PMID- 16466274
TI  - The Australian health policy changes of 1999 and 2000: an evaluation.
AB  - This article evaluates three measures introduced by the Australian Federal
      Government in 1999 and 2000 that were designed to encourage private health
      insurance and relieve financial pressure on the public healthcare sector. These
      policy changes were (i) a 30% premium rebate, (ii) health insurers offering
      lifetime enrolment on existing terms and the future relaxation of premium
      regulation by permitting premiums to increase with age, and (iii) a mandate for
      insurers to offer complementary coverage for bridging the gap between actual
      hospital billings and benefits paid. These measures were first evaluated in terms
      of expected benefits and costs at the individual level. In terms of the first
      criteria, the policy changes as a whole may have been efficiency-increasing. The
      Australian Government mandate to launch gap policies may well have created a
      spillover moral hazard effect to the extent that full insurance coverage
      encouraged policy holders to also use more public hospital services, thus
      undermining the government's stated objective to relieve public hospitals from
      demand pressure. Without this spillover moral hazard effect, there might have
      been a reduction in waiting times in the public sector. Secondly, the measures
      were evaluated in terms of additional benchmarks of the cost to the public purse,
      access and equity, and dynamic efficiency. Although public policy changes were
      found to be largely justifiable on the first set of criteria, they do not appear
      to be justifiable based on the second set. Uncertainties and doubts remain about
      the effect of the policy changes in terms of overall cost, access and equity, and
      dynamic efficiency. This is a common experience in countries that have considered
      shifts of their healthcare systems between the private and public sectors.

PMID- 16466275
TI  - The cost effectiveness of universal versus selective newborn screening for sickle
      cell disease in the US and the UK: a critique.
AB  - We reviewed several cost-effectiveness analyses that modelled the costs and yield
      of newborn screening for sickle cell disease (SCD) in the US and the UK and
      discuss the ways in which newborn screening policies in each country evolved with
      regard to the results of the analyses. Each of the reviewed studies compared the
      projected cost of universal screening with that of selective screening of
      children from specific ethnic groups. Despite variability in assumptions, the
      studies concurred that universal screening in areas with low SCD prevalence would
      result in a higher cost per case detected, compared with selective screening of
      children in high-risk ethnic groups. Investigators expressed differing opinions
      about the economic justification of universal screening, which reflected
      differences in the understanding of cost effectiveness and in how study questions
      were framed. Ultimately, policy makers in both countries decided in favour of
      universal screening, which appears to reflect a growing consensus that ethnically
      targeted newborn screening is not an acceptable public health strategy. One way
      to interpret this outcome is that considerations of equity and logistics,
      including potential stigmatisation, missed cases, and the perceived difficulty
      and discomfort in ascertaining ethnicity or in separating specimens, trumped
      economic calculations regarding the relative efficiency of targeted screening. It
      is not the case that policy makers explicitly favoured equity over economic
      optimisation; rather, they appear to have given more credence and value to the
      expert opinion of screening specialists than to the results of economic analyses.

PMID- 16466276
TI  - Determining priority for liver transplantation: a comparison of cost per QALY and
      discrete choice experiment-generated public preferences.
AB  - OBJECTIVE: A comparison of the implications of the application of the principles
      of equity and efficiency as two desirable but competing attributes of the organ
      allocation system. Efficiency is defined in economic terms as the standard cost
      per QALY model and equity considerations are included in a model based on public
      preferences generated from a discrete choice experiment in determining priority
      for donor liver graft allocation. METHODS: A survey of the general public (n =
      303) using a discrete choice experiment was undertaken. The results enabled
      estimation of the relative weights attached to several key factors which might be
      used to prioritise patients on the waiting list for liver transplantation. These
      weights were then used to develop a patient-specific index (PSI) for all patients
      diagnosed with one of three main chronic liver diseases who had received a liver
      transplant during an 18-month period at all Department of Health designated liver
      transplant centres in England and Wales (n = 207). The cost per QALY model
      comprised net total costs from assessment to 27 months following assessment as
      the numerator of the ratio. Net survival over the same time period, adjusted for
      HR-QOL using population values for the EQ-5D descriptive system, formed the
      denominator. RESULTS: Priority for liver transplantation differed markedly
      according to whether patients were ranked according to efficiency (net cost per
      QALY) or equity considerations (PSI) and the differences in ranks were found to
      be statistically significant (Wilcoxon signed rank test p < 0.001). CONCLUSIONS:
      This study emphasises that the priorities of the general public may not accord
      with those arising from a pure efficiency objective and quantifies the extent of
      the efficiency loss in terms of lost QALYs and increased net programme costs
      associated with the incorporation of equity concerns as reflected in public
      preferences for the allocation of donor livers for transplantation.

PMID- 16466277
TI  - The incremental cost effectiveness of withdrawing pulmonary artery catheters from
      routine use in critical care.
AB  - OBJECTIVE: The objective of this study was to conduct an economic evaluation to
      identify any differences in the expected costs and outcomes between patients
      treated with pulmonary artery catheters (PACs) and those without, in order to
      better inform healthcare decision makers. METHOD: The evaluation was carried out
      alongside a clinical trial investigating the use of PACs in intensive care units
      (ICUs) in the UK. It was conducted from the perspective of the UK NHS, in which
      PACs are an established intervention. Treating patients without using a PAC was
      characterised as the new intervention. The primary outcome measure was QALYs. The
      secondary outcome measure was hospital mortality. NHS costs per patient were
      calculated for the financial year 2002/03. The bootstrap method was used to
      characterise the uncertainty of the results and to construct cost-effectiveness
      acceptability curves. RESULTS: The cost per QALY and per life gained from the
      withdrawal of PACs were Pounds 2892 and Pounds 21,164, respectively. CONCLUSION:
      The results of this study indicate that withdrawal of PACs from routine clinical
      use in ICUs within the NHS would be considered cost effective in the current
      decision-making climate.

PMID- 16466278
TI  - Health promotion/disease prevention to the rescue! Tempering the giant, geriatric
      tsunami.

PMID- 16466279
TI  - Separation of nail plate from nail bed. There is no previous history of other
      skin conditions.

PMID- 16466280
TI  - Health promotion in older adults: the role of lifestyle in the metabolic
      syndrome.
AB  - The metabolic syndrome, also known as dysmetabolic syndrome, Syndrome X, or
      insulin resistance syndrome, is an amalgam of obesity-related health risks that
      significantly increases the chance of developing diabetes, coronary artery
      disease, and stroke. Progress in understanding the metabolic syndrome has
      confirmed the importance of metabolic imbalances in the development of serious
      and chronic cardiovascular, neurologic, immunologic, renal, and endocrine
      diseases. Crucial to planning treatment is the understanding that the metabolic
      syndrome is largely a disorder caused by behavior, thus its most important
      therapeutic intervention entails lifestyle change: Significant behavioral change
      can dramatically modify and even reverse all factors of the metabolic syndrome
      and its consequences. We examine the pathophysiology of the metabolic syndrome
      and provide strategies to encourage weight loss and dietary modifications and to
      promote increased physical activity.

PMID- 16466281
TI  - Medication adherence and cognition. Medical, personal and economic factors
      influence level of adherence in older adults.

PMID- 16466283
TI  - Enteral tube feeding and pneumonia.
AB  - To determine the effects of enteral tube feeding on the incidence of pneumonia,
      we performed a retrospective review of all clients at our institution who had
      gastrostomy or jejunostomy tubes placed over a 10-year period. Ninety-three
      subjects had a history of pneumonia before feeding tube insertion. Eighty had
      gastrostomy and 13, jejunostomy tubes. There was a 45% decrease in the incidence
      of pneumonia in the year following tube insertion compared to the prior year.
      This improvement was seen in gastrostomy and in jejunostomy tubes, but was only
      statistically significant in gastrostomy tubes. We conclude that although feeding
      tubes do not completely prevent pneumonia, there is an immediate decrease in the
      incidence of pneumonia following tube placement.

PMID- 16466282
TI  - Diathesis-stress and depressed mood among adults with mental retardation.
AB  - The impact of diatheses, stress, and their interaction on depressed mood was
      evaluated to determine the appropriateness of cognitive diathesis-stress models
      of depression for adults with mental retardation. We also tested hopelessness as
      a mediator in the prediction of depressed mood to evaluate the hopelessness
      theory of depression. Seventy-three adults with mental retardation and adequate
      receptive vocabulary participated in semi-structured interviews. Experiencing
      life stressors and possessing a negative attributional style, but not their
      interaction, served as predictors of depressed mood. Similar results were
      obtained using frequency or impact ratings of life stress. Conditions were not
      met to test hopelessness as a mediator. Treatment implications for depression
      among adults with mental retardation are highlighted.

PMID- 16466284
TI  - Mother-child relationship quality among adolescents and adults with autism.
AB  - The mother-child relationship in families of 202 adolescents and adults with an
      autism spectrum disorder living at home and its association with maternal
      caregiving gains and strains were examined. Findings indicate a wide range of
      variability in the quality of the mother-child relationship, although most were
      characterized as positive across multiple measures. Characteristics of the son or
      daughter with autism (less severe maladaptive behaviors, better health, and less
      social impairments) and characteristics of the mother (lower levels of pessimism)
      were predictive of more positive mother-child relationships. In turn, specific
      aspects of the mother-child relationship (greater positive affect and warmth),
      along with other child and maternal characteristics, predicted fewer maternal
      caregiving strains and, to a lesser extent, greater caregiving gains.

PMID- 16466285
TI  - Association between differentiated processing of syllables and comprehension of
      grammatical morphology in children with Down syndrome.
AB  - Our purpose in this exploratory investigation was to examine the relationship
      between degree of impairment in grammatical morpheme comprehension and event
      related potential measures of differentiated processing of speech syllables in 10
      children with Down syndrome. Results strongly support the hypothesized
      association. Graphs of the association indicate that children with less impaired
      grammatical comprehension had greater amplitude differences in event-related
      potentials to contrast of syllables within preselected poststimulus latency
      ranges. The theoretical and clinical ramifications of these results are
      discussed.

PMID- 16466288
TI  - Frequent aggression and attribution of hostile intent in people with mild to
      moderate intellectual disabilities: an empirical investigation.
AB  - We investigated whether aggressive individuals have an attributional bias of
      hostile intent compared to nonaggressive peers. We compared 43 frequently
      aggressive individuals who had mild to moderate intellectual disabilities with 46
      nonaggressive controls on an attributional task. The aggressive participants
      attributed significantly more hostile intent to protagonists and indicated that
      they would respond more aggressively than did the controls to provocative scenes,
      but only when the threat was to themselves. Results suggest that differences in
      attribution of threat to self play a role in frequent aggression. These
      differences appear to be due, in part, to a positive bias of the nonaggressive
      participants on the self-referent scenes. Clinically, results highlight the
      importance of assessing and addressing aggressive individuals' interpersonal
      perceptions.

PMID- 16466287
TI  - Socioemotional understanding and frequent aggression in people with mild to
      moderate intellectual disabilities.
AB  - Aggression in a proportion of people with intellectual disabilities is often
      assumed to be due to social-cognitive deficits. We reported on two studies in
      which we compared the emotion recognition and perspective-taking abilities of 43
      frequently aggressive individuals and 46 nonaggressive peers. No difference was
      found between the groups' ability to label facial affect. The perspective-taking
      task required participants to distinguish between reactions of angry versus calm
      characters. Although both groups had similar success with elements of the task,
      the aggressive group proved better at predicting characters' attributions.
      Results suggest that deficits in emotion recognition and perspective-taking
      cannot be assumed to be causal or maintaining factors of frequent aggression.
      This has implications for assessment and treatment.

PMID- 16466291
TI  - Vascular dementia may be easier to treat than diagnose.

PMID- 16466293
TI  - Bipolar disorder: historic perspective, current pharmacologic treatment options
      and a review of quetiapine.
AB  - Bipolar disorder is a complex mental illness that is frequently both under
      diagnosed and under-treated. The symptoms of bipolar disorder can be confused
      with other medical illnesses or drug effects or may even be overlooked entirely
      as extreme character traits. The consequences of delayed diagnosis or
      misdiagnosis are potentially devastating, including loss of employment, impaired
      relationships and a severely impaired quality of life. This article will review
      the historic perspectives of bipolar disorder, the diagnostic criteria for the
      phases of the illness, and the pharmacologic options available to treat this
      condition. Quetiapine, an atypical antipsychotic, will be reviewed indepth. Based
      on extensive trial data, reviewed in this article, quetiapine is approved by the
      US Food and Drug Administration for use as monotherapy or as adjunctive therapy
      with other mood stabilizers for the treatment of acute manic episodes of bipolar
      I disorder. Clinical trials describing the efficacy of quetiapine in other phases
      of bipolar disorder and in other patient populations are also reviewed. A
      discussion of the drug profile of quetiapine includes its chemistry,
      availability, pharmacodynamics, pharmacokinetics and metabolism. Preclinical
      studies, postmarketing surveillance, safety, tolerability and regulatory issues
      are also evaluated. Finally, potential future directions for quetiapine are
      discussed, together with a review of key issues in bipolar disorder management
      and details of the information resources used in preparing this article.

PMID- 16466294
TI  - The 'afterthought' diagnosis: rehabilitating adjustment disorders.
AB  - Although a common diagnosis, adjustment disorder has received little scientific
      attention, and instead the focus has been on major depression. It is likely that
      adjustment disorder and major depression have been conflated and the reasons for
      this are explored. Delineating one from the other clearly has crucial therapeutic
      and financial implications.

PMID- 16466295
TI  - The potential of stem cell therapies for neurological diseases.
AB  - As a novel neurotherapeutic strategy, stem cell transplantation has received
      considerable attention, yet little of this attention has been devoted to the
      probabilities of success of stem cell therapies for specific neurological
      disorders. Given the complexities of the cellular organization of the nervous
      system and the manner in which it is assembled during development, it is unlikely
      that a cellular replacement strategy will succeed for any but the simplest of
      neurological disorders in the near future. A general strategy for stem cell
      transplantation to prevent or minimize neurological disorders is much more likely
      to succeed. Two broad categories of neurological disease, inherited metabolic
      disorders and invasive brain tumors, are among the most likely candidates.

PMID- 16466296
TI  - The value of self-measured home blood pressure in predicting stroke.
AB  - Home blood pressure measurements more accurately and reliably reflect target
      organ damage and the prognosis of cardiovascular disease than conventional blood
      pressure measurements. All evidence of the value of home blood pressure
      measurement in predicting stroke is currently derived from a population-based
      prospective study in Japan (the Ohasama study). The authors demonstrated that
      home blood pressure measurement provides more useful prognostic information on
      stroke than conventional blood pressure measurements. The predictive value of
      home blood pressure measurement increased progressively with the number of
      measurements. Even the initial-first home blood pressure values (one measurement)
      showed a significantly greater relation with stroke risk than conventional blood
      pressure values (mean of two measurements). Home blood pressure measurement
      increased the predictive power of categorizations of guidelines compared with
      conventional blood pressure measurement. Home blood pressure measurement is a
      useful tool to predict future risk of stroke.

PMID- 16466297
TI  - The effect of infections and vaccinations on stroke risk.
AB  - There is increasing evidence that, in addition to conventional risk factors,
      acute and chronic infectious diseases increase the risk of stroke. Acute
      infection, mainly respiratory, and both bacterial and viral infection, represent
      temporarily active trigger factors for cerebral ischemia. Chronic infectious
      diseases that may increase the risk of stroke include periodontitis, chronic
      bronchitis and infections with microbial antigens, such as Helicobacter pylori
      and Chlamydia pneumoniae. From observational studies, there is evidence that
      vaccination against influenza is associated with a reduced risk of stroke,
      myocardial infarction and all-cause mortality. This report provides an overview
      on the influence of infection on stroke risk and potential anti-infective
      strategies that may play a future role in stroke prevention.

PMID- 16466298
TI  - What's new in stroke prevention and treatment.
AB  - This review summarizes the latest results and developments in stroke prevention
      and acute treatment studies published in 2004 and 2005. In contrast to primary
      prevention in men, aspirin did not significantly reduce the risk of myocardial
      infarction or death from cardiovascular causes in women over 45 years of age.
      Patients with symptomatic intracranial stenosis do not benefit from secondary
      prevention with oral anticoagulation. Magnetic resonance-based acute stroke
      studies with recombinant tissue plasminogen activator (rtPA) or with
      desmoteplase, a new thrombolytic agent, showed similar safety and potential
      benefit beyond the 3-h time window, as with the established inclusion criteria of
      rtPA. The surgical trial in intracerebral hemorrhage (STICH) failed to
      demonstrate any benefit for early operative evacuation of hematoma. The authors
      aim to provide a wide overview of stroke prevention and acute treatment studies
      published in 2004 and 2005. Relevant journals were hand-searched to compile a
      broad, but not comprehensive, summary of innovative and clinically relevant
      findings. A short critical evaluation at the end of selected reviews should
      encourage the reader to further reading of studies of interest.

PMID- 16466299
TI  - Statins in stroke: prevention, protection and recovery.
AB  - Stroke is the third most common cause of death and the leading cause of
      neurological disability in the USA. While some risk factors for stroke, such as
      hypertension and cigarette smoking, are well defined, the role of cholesterol in
      stroke pathogenesis is debated. However, numerous studies in the past decade have
      shown that medications that reduce cholesterol via 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibition (statins) reduce the incidence of ischemic stroke
      in patients who are known to have, or be at high risk of, coronary artery
      disease. In addition, statins may have benefits in neuroprotection and recovery
      after stroke. The mechanisms by which statins protect against, and improve
      outcome after, stroke probably extend beyond lipid lowering.

PMID- 16466300
TI  - Blood pressure control and prevention of stroke.
AB  - Hypertension is an important risk factor for stroke. The latter results in
      disability and premature death and represents a major public health problem.
      Various studies have established a strong relationship between increasing blood
      pressure and stroke risk, as well as clear evidence of a reduction in the
      incidence of strokes in response to even relatively small decreases in blood
      pressures. In this review, the pharmacological treatment of hypertension and the
      benefit on stroke prevention is outlined.

PMID- 16466301
TI  - Strategies for managing symptoms of anxiety.
AB  - The purpose of this article is to summarize strategies for effectively managing
      the symptoms of anxiety. The distinction between the cognitive, physiological and
      behavioral components of fear and anxiety is explained and various treatment
      targets are outlined. Empirically-supported strategies that are effective in
      alleviating common symptoms of anxiety are reviewed. These include various forms
      of psychosocial intervention (i.e., cognitive and behavioral therapies),
      pharmacotherapy, in addition combined treatment approaches. Expert consensus
      guidelines, prognostic factors, patient preferences and accessibility issues are
      discussed with regard to treatment selection in addition to emerging challenges
      in the field and future research directions.

PMID- 16466302
TI  - Silencing neurodegenerative disease: bringing RNA interference to the clinic.
AB  - RNA interference (RNAi) is a recently described conserved biological pathway
      where non-coding RNAs suppress the expression of specific genes. Research efforts
      in the RNAi field aim to gain a better understanding of how its underlying
      machinery is orchestrated, to define the biological role of this conserved
      pathway, determine how to effectively manipulate RNAi in the laboratory and to
      integrate all this knowledge to develop novel therapies for human disease. This
      review summarizes the advances in the design of therapeutic RNAi for
      neurodegenerative diseases and discusses some of the experimental steps required
      to bring this therapy to human clinical trials.

PMID- 16466303
TI  - Long-term adaptive changes induced by serotonergic antidepressant drugs.
AB  - The development of conventional antidepressants has been largely based on the
      hypothesis of monoaminergic dysfunctions and focuses particularly on the
      serotonin 5-hydroxytryptamine (5-HT) system. Hence, various classes of
      antidepressant treatments enhance 5-HT neurotransmission with a time course
      consistent with their delayed therapeutic effect. This delayed onset appears to
      be associated with the gradual development of specific adaptive changes of
      functional 5-HT receptors. However, recent theories suggest that major depressive
      disorders may be associated with impairments of functional plasticity and
      cellular flexibility. This review discusses several physiological mechanisms by
      which 5-HT function and hippocampal neuroplasticity are regulated. Knowledge of
      these long-term adaptations will increase not only our understanding of
      pathological processes underlying affective disorders, but could also lead to the
      development of new strategies to treat these devastating illnesses.

PMID- 16466304
TI  - Neurofeedback treatment of epilepsy: from basic rationale to practical
      application.
AB  - The treatment of epilepsy through operant conditioning of the sensorimotor rhythm
      electroencephalogram has a 35-year history. Neurophysiological studies have shown
      that this phasic oscillation reflects an inhibitory state of the sensorimotor
      system. Operant learning of sensory motor rhythm production results in an
      upregulation of excitation thresholds within the thalamocortical sensory and
      motor circuitry, which in turn is associated with reduced susceptibility to
      seizures. The clinical benefits derived from this neurofeedback training
      protocol, particularly in patients that are nonresponsive to pharmacotherapy,
      have been documented in many independent laboratories. Recent advances in
      computer technology have resulted in the availability of relatively inexpensive
      high-quality equipment for the application of neurofeedback therapy, thus
      presenting a viable and promising treatment alternative to the interested
      clinician.

PMID- 16466305
TI  - Targeted therapy for malignant glioma: neural stem cells.

PMID- 16466307
TI  - Tetrabenazine in the treatment of hyperkinetic movement disorders.
AB  - Tetrabenazine, a dopamine-depleting agent first synthesized half a century ago,
      was initially developed for the treatment of schizophrenia. Although psychotic
      disorders have since been treated more successfully with other neuroleptic
      medications, many studies have shown this drug to be effective in the treatment
      of hyperkinetic movement disorders (hyperkinesias). Hyperkinesias are neurologic
      disorders characterized by abnormal involuntary movements such as chorea
      associated with Huntington's disease, tics in Tourette's syndrome and
      stereotypies in tardive dyskinesia. Recently, clinical trials investigating
      tetrabenazine for the treatment of chorea associated with Huntington's disease
      found the drug to be safe and efficacious, making approval by the US Food and
      Drug Administration for this indication a distinct possibility.

PMID- 16466308
TI  - Topiramate for the treatment of epilepsy and other nervous system disorders.
AB  - Initially synthesized as an oral hypoglycemic agent, topiramate was approved for
      use as an anticonvulsant in 1996. Its broad spectrum efficacy in epilepsy,
      including as monotherapy and in children, is well established. Topiramate has
      also been used in the management of nonepileptic neurologic and psychiatric
      conditions, including migraine prophylaxis (with firmly established efficacy),
      obesity (with some evidence of long-term maintenance of weight loss), substance
      dependence, bipolar disorder and neuropathic pain, and it has been investigated
      as a possible neuroprotective agent. Paresthesias and cognitive side effects are
      the most common troublesome adverse effects. Recent trends towards lower doses
      may help achieve the best combination of efficacy and tolerability.

PMID- 16466309
TI  - Olanzapine/fluoxetine combination for bipolar depression.
AB  - Bipolar depression remains one of the most difficult to treat of all mental
      disorders. Until recently, no treatments, including antidepressants, have
      consistently shown to be effective in this condition. Olanzapine, an atypical
      antipsychotic, has been approved by the US Food and Drug Administration for the
      acute treatment of mania and maintenance prevention of relapse into depression or
      mania. A clinical trial tested the relative effectiveness of the combination of
      olanzapine and fluoxetine in bipolar type I depression, against olanzapine alone
      or placebo. The combination produced a very robust clinical effect acutely and a
      long-term follow-up study indicated that there was a low rate of induction of
      mania or mixed states. Therefore, the olanzapine/fluoxetine combination
      represents a viable alternative for bipolar depression. However, uptake of this
      combined product in practice has been modest. This is likely to be the result of
      several factors, including resistance to the use of fixed combination
      preparations and, more recently, evidence of effectiveness of the atypical
      quetiapine and the anticonvulsant lamotrigine. Perhaps the greatest resistance to
      the use of olanzapine alone or in combination has been the problem of weight gain
      and the attendant risk of type 2 diabetes and the metabolic syndrome. Vigorous
      management of this problem has been shown to mitigate the potential for weight
      gain and is required if this combination is to be used. However, many clinicians
      find management of weight gain in olanzapine treated patients a challenge. In
      addition, weight, waist circumference, lipids and glucose should be monitored.

PMID- 16466310
TI  - Depression and randomized, controlled trials: problems and solutions.
AB  - Research into what works in depression is in trouble. All treatments appear
      equally effective and what happens in research trials does not seem to translate
      into clinical practice or, to put it another way, clinical practice is not
      reflected in randomized controlled trials. We run the risk of designing cosmetic
      trials with no real relationship to clinical services that only serve to
      demonstrate that new treatments are effective in artificial settings. This
      article outlines possible reasons for this, which include how depression is
      diagnosed, how people are recruited into trials, the design of trials and how
      outcomes are assessed. The solutions to these problems involve changing how
      patients are recruited, considering other trial designs and using different
      outcome measures.

PMID- 16466311
TI  - Symptoms versus neurocognitive skills as correlates of everyday functioning in
      severe mental illness.
AB  - A critical review of cross-sectional and longitudinal studies conducted from 2001
      2005 investigating the relationship of symptoms and neurocognitive skills to
      everyday functioning in patients with severe mental illness was completed.
      Literature and bibliographic searches identified seven studies, which were
      grouped according to the methodology of measurement of everyday function
      selected: clinician-rated scales of psychosocial function based on patient and
      proxy report; performance-based measures of functional capacity; or competitive
      vocational success. Results of the review revealed that negative symptoms, such
      as social withdrawal, psychomotor slowing and blunted affect, and neurocognitive
      measures of attention, executive function, working memory, verbal memory and
      psychomotor speed, were most commonly linked to all three domains of everyday
      function. With the exception of one study, there was no evidence of a
      relationship between positive symptoms, such as delusions and hallucinations, and
      everyday function. The implications of these findings for guiding future research
      are discussed.

PMID- 16466313
TI  - Late-life depression: a neuropsychiatric approach.
AB  - Late-life depression refers to depressive syndromes defined in the American
      Psychiatric Association's Diagnostic and Statistical Manual and in the
      International Classification of Diseases that arise in adults older than 65 years
      of age. Late life depressive syndromes often arise in the context of medical and
      neurologic disorders. There is a high prevalence of depression in various
      neurodegenerative disorders such as Alzheimer's disease, Lewy body disease,
      Parkinson's disease, cerebrovascular disease and frontotemporal dementias. It has
      been well recognized that late life depression may itself be the presenting
      symptom of a latent neurodegenerative disorder. Therefore, an accurate diagnosis
      of late-onset depression may serve to identify a high-risk group that would
      benefit from initiation of therapies with the goal of delaying or possibly even
      preventing the onset of dementia.

PMID- 16466312
TI  - Antipsychotic drug action: targets for drug discovery with neurochemical imaging.
AB  - Schizophrenia is a serious lifelong mental illness for which current treatments
      may only be partially effective. All antipsychotic medications available at
      present are thought to exert their main antipsychotic effect through antagonism
      of dopamine D2 receptors. Clozapine is the most effective antipsychotic drug
      currently available, but it can cause serious side effects, including
      agranulocytosis and diabetes. Pharmacologic factors that distinguish clozapine
      from other antipsychotic drugs have been studied to try to develop safer drugs
      with similar efficacy to clozapine. These have met with limited success.
      Neurochemical imaging techniques, such as positron emission tomography, single
      photon emission tomography and magnetic resonance spectroscopy, have been used to
      study antipsychotic drug action in living human subjects. These techniques shed a
      great deal of light on the mechanisms of antipsychotic action and have revealed a
      number of novel targets for future drug development in schizophrenia. Next
      generation antipsychotic medications will aim to improve on the efficacy and
      tolerability of currently available medications. The authors believe that they
      are likely to achieve this through drug action at non-D2 sites. Future research
      and drug development, including the development of medications to prevent
      progression from the prepsychotic stage to schizophrenia, will rely heavily on
      neurochemical imaging methods at all stages in the drug-discovery pipeline.

PMID- 16466314
TI  - Current and emerging somatic treatment strategies in psychotic major depression.
AB  - Psychotic major depressive disorder (MDD) is a mood disorder characterized by
      severe affective and neurovegetative symptoms together with the presence of
      delusions and/or hallucinations. It is a common disorder seen in a quarter of
      consecutively admitted depressed patients and is often associated with severe
      symptomatology, increased suicide risk, poor acute response to antidepressants
      and poor acute and long-term treatment outcome. It is possible that poor response
      in psychotic depression is caused by the fact that we have yet to identify the
      most efficacious treatment protocol for psychotic MDD. Multiple studies have
      shown that modifications in the treatment paradigm may increase treatment
      efficacy in psychotic MDD. It has been generally accepted that, during the acute
      treatment phase, antidepressant-antipsychotic drug combination therapy is more
      effective than either treatment alone, although this strategy has recently been
      challenged. The question of the optimal duration of pharmacotherapy in order to
      prevent relapse and improve long-term (i.e., 5-year) outcome is a focus of
      current investigation. This article will review currently recommended treatment
      strategies for the acute, continuation and maintenance phases of therapy. In
      particular, it will address the role of newer-generation antidepressants, the
      role of second-generation antipsychotics, the use of mood stabilizers and
      indications for electroconvulsive therapy. Other possible treatment strategies
      such as transcranial magnetic stimulation, vagus nerve stimulation, deep-brain
      stimulation and glucocorticoid receptor antagonists will be discussed. Current
      recommendations for the prevention of relapse and improvement of long-term
      outcome will be reviewed.

PMID- 16466315
TI  - Dopamine agonists in the treatment of Parkinson's disease.
AB  - Dopamine agonists are highly effective as adjunctive therapy to levodopa in
      advanced Parkinson's disease and have rapidly gained popularity as a monotherapy
      in the early stages of Parkinson's disease for patients less than 65-70 years
      old. In the latter case, dopamine agonists are about as effective as levodopa but
      patients demonstrate a lower tendency to develop motor complications. However,
      dopamine agonists lose efficacy over time and the number of patients remaining on
      agonist monotherapy decreases to less than 50% after 3 years of treatment. Thus,
      after a few years of treatment the majority of patients who started on dopamine
      agonists will be administered levodopa, in a combined dopaminergic therapy, in
      order to achieve a better control of motor symptoms.

PMID- 16466316
TI  - Parkinson's disease management strategies.
AB  - Parkinson's disease (PD) treatment strategies should consider each patient
      individually. Drug therapy is the mainstay of treatment. An average 62-year-old
      male first diagnosed with PD will likely live for 20 years and treatment should
      be geared for long-term control of symptoms and quality of life. Of the currently
      available drugs, none are neurotoxic to the human substantia nigra and none are
      neuroprotective. As PD is a progressive disorder, all drugs have adverse effects
      and reduced efficacy with time. PD patients need regular follow-ups to make
      necessary medication adjustments. There is no perfect treatment. The authors have
      discussed their treatment methods and the reasoning behind it. Depending on the
      patient's age, the predominant symptoms and quality of life, treatment is
      individualized. In an average patient the least potent drugs, such as
      anticholinergics or amantadine, are administered first adding a dopamine agonist
      later on. Levodopa (LD) remains the most useful drug for PD and is reserved for
      later stages of disease. The objective is to keep the patient at Hoehn and Yahr
      Stage 2.0 or lower level of disability (bilateral findings with preserved
      postural reflexes) during off-stage and to avoid adverse effects. There is no
      long-term difference between standard preparations and control release
      formulations of LD/carbidopa or LD/benserazide. In older subjects, the first
      choice is LD. In patients who cannot be managed medically, surgical treatment is
      an option in selected patients (nondemented, <70 years old, previous good LD
      response). The surgical treatment of choice is currently subthalamic nucleus deep
      brain stimulation. Physiotherapy, occupational therapy and speech therapy are
      valuable in advanced PD cases.

PMID- 16466317
TI  - Neural stimulation for Parkinson's disease: current therapies and future
      directions.
AB  - Neural stimulation has rapidly become an integral tool in the treatment of
      Parkinson's disease and other movement disorders. Today it serves as an important
      adjunct to medical therapy that continues to gain applicability to patients in
      whom the disease has progressed significantly. Studies have demonstrated efficacy
      in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up
      times. Continuing study is teaching us more about the mechanism of deep-brain
      stimulation effect. New targets, which may treat the disease more successfully,
      are being examined. In this review, the history of deep-brain stimulation, the
      rationale for the known targets of stimulation; the clinical evidence
      demonstrating their benefit and, finally, future perspectives on new treatments
      that are being investigated and may have an impact on the field are discussed.

PMID- 16466318
TI  - Quality of life for patients with epilepsy is determined by more than seizure
      control: the role of psychosocial factors.
AB  - Antiepileptic drugs remain the cornerstone of epilepsy treatment for minimizing,
      if not eliminating, seizures. However, many factors other than the degree of
      seizure control influence the quality of life for patients with epilepsy. This
      review focuses on psychosocial factors that have been associated with quality of
      life in this population, especially mood disorders, stigma seizure worry, self
      esteem and self-mastery. Irrespective of their level of seizure control from
      antiepileptic drugs, patients may also benefit from targeted psychosocial
      interventions that reduce the negative impact of these factors on their quality
      of life.

PMID- 16466321
TI  - Effects of discontinuing stavudine or protease inhibitor therapy on human
      immunodeficiency virus-related fat redistribution evaluated by dual-energy x-ray
      absorptiometry.
AB  - STUDY OBJECTIVE: To determine whether discontinuation of stavudine or protease
      inhibitor therapy improves human immunodeficiency virus (HIV)-related fat
      distribution in men. DESIGN: Observational, retrospective study consisting of a
      cross-sectional (part 1) and a longitudinal (part 2) study. DATA SOURCE: Medical
      records from Purpan University Hospital and La Grave University Hospital,
      Toulouse, France. Subjects. Eighty men with HIV infection treated with
      antiretrovirals and 151 healthy male controls matched for age. MEASUREMENTS AND
      MAIN RESULTS: In part 1, body composition and fat distribution of the HIV
      infected men were compared by dual energy x-ray absorptiometry (DEXA) with those
      of the controls to determine whether body fat distribution is altered in HIV
      infected men. In part 2, we analyzed modifications of body composition and fat
      distribution in 45 of the 80 patients. These 45 had been exposed to
      antiretroviral drugs, including stavudine and a protease inhibitor, for at least
      5 months before the first of two DEXA assessments. They received three different
      treatment strategies for several months. In group 1, stavudine was withdrawn; in
      group 2, protease inhibitor was discontinued, and in group 3, stavudine plus
      protease inhibitor were continued. Group 1 showed a significant fat gain in the
      lower extremities 31.7 +/- 5.9 months after stavudine discontinuation (p<0.0001).
      Group 2 did not show any significant modification of total body, lower limb, or
      trunk fat despite protease inhibitor discontinuation for 35.2 +/- 6.6 months.
      Findings were similar for group 3, who continued receiving stavudine-protease
      inhibitor therapy for 21.2 +/- 12.8 months. CONCLUSION: These data suggest that
      long-term withdrawal of stavudine from the antiretroviral therapy regimen may be
      associated with significant improvement in lipoatrophy in the lower extremities,
      whereas long-term protease inhibitor withdrawal did not modify fat distribution.

PMID- 16466322
TI  - Do randomized controlled trials always trump case reports? A second look at
      propranolol and depression.
AB  - STUDY OBJECTIVE: To explore reasons for discrepancies between findings from case
      reports and those from a meta-analysis of randomized controlled trials regarding
      the association between beta-adrenergic blockers and depression. DESIGN:
      Systematic review. DATA SOURCE: PubMed/MEDLINE database. MEASUREMENTS AND MAIN
      RESULTS: We reviewed 24 published case reports showing an association between
      beta-blockers and depression and eight randomized controlled trials included in a
      meta-analysis of the adverse effects of these drugs. We abstracted the beta
      blocker taken, patients' age and sex, diagnoses, history of depression, type of
      depressive symptoms reported, and method and timing of the assessment of
      depression. Naranjo criteria were used to evaluate the strength of evidence from
      each case report for a possible association between beta-blockers and depression.
      Twelve case reports had a Naranjo score of 5 or more (suggesting a likely causal
      relationship), nine of which involved propranolol. In all nine, depression began
      soon after treatment, and in four, the patient had a history of depression. Three
      randomized controlled trials assessed propranolol. Depression rates in the
      control groups of these studies differed substantially from each other (0-40%,
      p<0.0001). In only one randomized controlled trial did investigators assess
      depression systematically; they evaluated depression after 1 year of treatment
      and eliminated patients who had previously been prescribed an antidepressant.
      CONCLUSION: A criterion standard to assess the true relationship between beta
      blockers and depression is lacking. Factors such as the lack of systematic
      assessment of depression, the timing of assessments, and the selection of
      patients may have reduced the ability of researchers in the randomized controlled
      trials to detect depression as an adverse effect. Evidence from case reports
      should be carefully considered when relevant randomized controlled trials have
      not been adequately designed to detect adverse effects.

PMID- 16466323
TI  - Implications of rosiglitazone and pioglitazone on cardiovascular risk in patients
      with type 2 diabetes mellitus.
AB  - Clinical data suggest that thiazolidinediones--specifically, rosiglitazone and
      pioglitazone--may improve cardiovascular risk factors through multiple
      mechanisms. Low insulin sensitivity has been described as an independent risk
      factor for coronary artery disease and cerebrovascular disease. Patients with
      insulin resistance often have several known risk factors, such as obesity,
      dyslipidemia, and hypertension. Other emerging risk factors may be prevalent in
      patients with insulin resistance, such as hyperinsulinemia, elevated C-reactive
      protein, elevated plasminogen activator inhibitor levels, and small, dense, low
      density lipoproteins. The only available drug class that primarily targets
      insulin resistance is the thiazolidinediones. These drugs have shown efficacy in
      affecting surrogate markers of cardiovascular risk in patients with diabetes
      mellitus. Alterations in these risk factors are likely due to their effects on
      improving insulin sensitivity and/or glycemic control. Trials to assess whether
      thiazolidinediones actually reduce cardiovascular outcomes are continuing.

PMID- 16466324
TI  - Cerebral vasospasm after aneurysmal subarachnoid hemorrhage: an overview of
      pharmacologic management.
AB  - Cerebral vasospasm remains one of the leading causes of mortality in patients who
      experience a subarachnoid hemorrhage but survive the initial 24 hours. Vasospasm
      generally occurs 3-4 days after the initial subarachnoid hemorrhage and peaks at
      5-7 days. The pathophysiology of vasospasm is poorly understood, which directly
      contributes to the inconsistency of management and creates a formidable challenge
      in clinical practice. Traditionally, hemodilution, hypervolemia, and induced
      hypertension (so-called triple H therapy); calcium channel blockers; and
      endovascular therapy have been used as either prophylactic therapy or treatment.
      However, management of vasospasm varies among physicians and institutions mainly
      because of a lack of large clinical trials and inconsistent results. Practice has
      been based primarily on case reports and the preference of each practitioner.
      Several experimental therapies have been explored; however, large, prospective,
      randomized controlled trials are needed to elucidate the role of these therapies.

PMID- 16466325
TI  - Optimizing antibiotic treatment for ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP) is the most common infectious complication
      in patients receiving mechanical ventilation and accounts for exorbitant use of
      resources in the intensive care unit. Antimicrobial management of VAP
      incorporates an initial broad-spectrum, empiric regimen to ensure appropriate
      coverage with deescalation of therapy after 48-72 hours based on culture results
      and sensitivities. When VAP clinically responds to treatment, antimicrobials
      should be discontinued after 7-8 days to reduce overall antibiotic consumption
      and the selection pressure on flora observed in the intensive care unit and thus
      minimize the development and spread of antimicrobial resistance.

PMID- 16466326
TI  - Barriers to glucose control in the intensive care unit.
AB  - Despite published evidence supporting glycemic control in critically ill
      patients, achieving euglycemia remains a problem in the intensive care units
      (ICUs) of many institutions. Clinicians seeking to implement the findings of
      published evidence in their practice face many potential barriers that make
      euglycemia difficult to achieve in patients in the ICU. Developing a
      comprehensive understanding of the many barriers to ICU glucose control can aide
      clinicians in attempting to change practice and improve patient outcomes.
      Barriers to ICU glucose control include the role of different health
      professionals in glucose management, communication among health care
      professionals, guidelines, protocols, ICU culture, fear of hypoglycemia, glucose
      monitoring, education, systems analysis, health care resources, nutritional
      needs, and drug utilization. By ensuring compliance, changing ICU culture,
      developing guidelines and protocols, and incorporating a multidisciplinary
      approach, clinicians can achieve glycemic control in the critically ill
      population and improve patient outcomes.

PMID- 16466327
TI  - Treatment of heparin-induced thrombocytopenia: is there a role for bivalirudin?
AB  - The recognition and management of heparin-induced thrombocytopenia (HIT) and
      heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) has been
      evolving over the past several years. Although HIT is a relatively uncommon
      adverse event in patients receiving heparin therapy, it bears a significant risk
      of thrombotic events. If patients are left untreated, 50% can develop thrombosis.
      Several direct thrombin inhibitors have been studied as alternative
      anticoagulants in patients with HIT. Lepirudin and argatroban are both approved
      by the United States Food and Drug Administration (FDA) for the management of
      HIT. Lepirudin requires dosage adjustments in patients with renal insufficiency
      and has potential for antibody formation. Argatroban requires dosage adjustments
      in patients with hepatic insufficiency. Argatroban increases the international
      normalized ratio when coadministered with warfarin, leading to dosage
      difficulties when transitioning to warfarin therapy. Bivalirudin is the most
      recent direct thrombin inhibitor to be introduced to the market, but it is not
      currently FDA approved for HIT. Controversy still exists over which direct
      thrombin inhibitor to use, especially in acutely ill patients and in those
      requiring invasive or surgical procedures. Bivalirudin has a relatively short
      half-life and a predictable response, which makes it attractive as an
      anticoagulant in patients requiring invasive or surgical procedures, those who
      are acutely ill, or patients with both renal and hepatic insufficiency. It offers
      promise as an additional direct thrombin inhibitor for use in patients with HIT,
      but additional studies need to be performed to further define its use.

PMID- 16466328
TI  - Reduced-dose rasburicase in the treatment of adults with hyperuricemia associated
      with malignancy.
AB  - Tumor lysis syndrome is a life-threatening complication of chemotherapy for
      patients with leukemia and large tumors with a high proliferative index, such as
      Burkitt's lymphoma. The syndrome is characterized by hyperkalemia,
      hyperphosphatemia, hypocalcemia, and hyperuricemia. The standard of care for
      hyperuricemia consists of hydration with or without alkalinization and
      administration of allopurinol. When treated in this manner, patients often
      experience persistent hyperuricemia that lasts several days after the start of
      antineoplastic therapy; sometimes they develop uric acid nephropathy as a
      consequence. Rasburicase, a recombinant urate oxidase enzyme, quickly removes
      large amounts of uric acid from plasma. The drug is approved by the United States
      Food and Drug Administration for management of elevated plasma uric acid levels
      in pediatric patients with leukemia, lymphoma, or solid tumor malignancies who
      are receiving chemotherapy. We undertook a retrospective review of adult patients
      treated with a single dose of rasburicase 6 mg for hyperuricemia associated with
      malignancy. Ten patients received one 6-mg dose of rasburicase, and one patient
      received two 6-mg doses as an adjuvant therapy to normalize uric acid levels. In
      most of the patients, a single 6-mg dose of rasburicase was effective in
      correcting uric acid levels in the typical time between diagnosis and start of
      antineoplastic therapy.

PMID- 16466329
TI  - Clinical impact of a pharmacist-managed diabetes mellitus drug therapy management
      service.
AB  - STUDY OBJECTIVE: To evaluate the impact of clinical pharmacist interventions,
      including drug therapy management, on outcomes relevant to diabetes mellitus.
      DESIGN: Retrospective chart review. SETTING: Ambulatory, multispecialty physician
      group practice within a managed care environment in suburban Chicago, Illinois.
      PATIENTS: Three hundred sixteen patients aged 18 years or older, with a diagnosis
      of diabetes mellitus (89% with type 2), who were referred to a clinical pharmacy
      service. INTERVENTION: Drug therapy management and education service provided by
      a clinical pharmacist. MEASUREMENTS AND MAIN RESULTS: Data were collected for
      glycosylated hemoglobin A(1c) (A1C), blood pressure, and low-density lipoprotein
      cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride
      concentrations. Data also were collected regarding patient adherence with
      American Diabetes Association guidelines for preventive care, including annual
      eye and foot examinations, influenza shots, and daily aspirin use at both
      baseline and follow-up. Mean +/- SD A1C reduction was 1.4% +/- 1.94% (p<0.001);
      the percentage of patients whose A1C was at goal level at baseline (< 7%)
      increased from 14.8% to 43.2% (p<0.001). Mean +/- SD LDL level reduction was 14
      +/- 41.1 mg/dl (p=0.002), mean +/- SD triglyceride level reduction 42 +/- 97.6
      mg/dl (p<0.001). The percentage of patients who reached goal for LDL level (< 100
      mg /dl), HDL level (> 40 mg/dl), and blood pressure (< 130/80 mm Hg) did not
      increase significantly from baseline, whereas those who reached the triglyceride
      level goal (< 150 mg/dl) increased from 36% to 55% (p<0.005). Frequency of annual
      dilated retinal examinations and monofilament foot examinations increased by 29%
      (p<0.05) and 12.5% (p<0.05), respectively. Daily aspirin use increased from 35%
      to 59% (p<0.05). CONCLUSION: Significant clinical improvement occurred in
      patients referred to the pharmacist in a diabetes drug therapy management
      program.

PMID- 16466330
TI  - Improving pharmacotherapy after myocardial infarction by group academic detailing
      using feedback data on a patient level.
AB  - STUDY OBJECTIVE: To develop and evaluate a peer review group (PRG) meeting using
      feedback data on a patient level to improve the quality of drug therapy for
      prevention of recurrent myocardial infarction. DESIGN: Prospective follow-up
      study. DATA SOURCE: General practitioners' computerized patients records
      (intervention patients) and the PHARMO record linkage system (controls).
      PATIENTS: Forty patients in the intervention group and 1030 control patients;
      both groups had documented myocardial infarction. INTERVENTION: The intervention,
      which was based on the principles of group academic detailing, consisted of
      scoring current cardiovascular treatment on separate forms for each patient,
      presenting an overview of, and discussing, evidence-based treatment after
      myocardial infarction, defining the target population, formulating a binding
      consensus, and identifying patients who were eligible for improvement of
      pharmacotherapy. MEASUREMENTS AND MAIN RESULTS: Drug therapy and adherence to the
      newly formulated PRG consensus were assessed at baseline and 1 year after the
      intervention. Of the patients who received the intervention and were not treated
      according to the PRG consensus at baseline, 40% received treatment according to
      the consensus 12 months after the PRG meeting. In the control group, the
      proportion of patients was 9.5% (prevalence ratio 4.2, 95% confidence interval
      1.8-9.7). CONCLUSION: Peer review group meetings can be a valuable tool for
      improving pharmacotherapy after myocardial infarction.

PMID- 16466331
TI  - Implementation of a self-administered questionnaire to identify patients at risk
      for medication-related problems in a family health center.
AB  - STUDY OBJECTIVE: To determine if a self-administered questionnaire can improve
      the identification of patients at risk for medication-related problems (MRPs)
      compared with usual methods of referral to a pharmacist. DESIGN: Prospective,
      randomized controlled study. SETTING: Multiprofessional primary care clinic at a
      tertiary care teaching hospital. PATIENTS: One hundred ninety-four ambulatory
      patients aged 18 years or older who were taking at least two drugs. MEASUREMENTS
      AND MAIN RESULTS: Patients completed a five-item, self-administered questionnaire
      modified from a tool that was previously validated in another population and
      statistically correlated with the risk of MRPs. Of 194 patients who completed the
      questionnaire, 89 were randomized to the control group (referral by usual
      methods) and 105 were referred according to their responses on the questionnaire
      (intervention group). Primary outcomes were the rate of referral and the number
      of at-risk patients identified. Referral rates were higher with the questionnaire
      than with usual methods (20% vs 6%, p=0.003). Of five patients referred by usual
      methods, one was at risk for MRPs according to questionnaire results. Of 84
      patients in the control group who were not referred, 12 (14%) were at risk
      according to the questionnaire results; this finding suggested that several at
      risk patients who were not referred by usual methods might have benefitted from a
      referral for a pharmacist's assessment. CONCLUSION: This self-administered
      medication risk assessment questionnaire effectively complemented the usual
      practices for identifying and referring patients at risk for MRPs.

PMID- 16466332
TI  - Drug interactions between linezolid and selective serotonin reuptake inhibitors:
      case report involving sertraline and review of the literature.
AB  - A 47-year-old woman developed confusion, incoordination, and hypertension after
      she was given linezolid in addition to sertraline for 5 days. Her symptoms
      resolved within 4 days of discontinuing linezolid. One and a half months later,
      she received a second course of linezolid; sertraline was discontinued on day 1
      of linezolid therapy. On day 9 of therapy, the patient developed confusion,
      myoclonus, and incoordination, and cardiopulmonary arrest occurred, leaving the
      patient in a coma. Diarrhea, hypertension, and tachycardia developed after
      cardiopulmonary arrest. Linezolid was discontinued on day 10, and cyproheptadine
      was given. Linezolid is a weak monoamine oxidase inhibitor and has been reported
      to interact with selective serotonin reuptake inhibitors (SSRIs). Several cases
      of serotonin syndrome in patients taking linezolid and SSRIs have been reported,
      including two reports with sertraline, one with paroxetine, four with citalopram,
      and two with fluoxetine. One abstract of a retrospective analysis reported that
      serotonin syndrome did not occur in patients who received linezolid and
      fluoxetine, paroxetine, or sertraline. Because of several limitations, however,
      no conclusions can be drawn from that retrospective analysis. A drug interaction
      involving escitalopram and linezolid has not been documented. Caution should be
      used when linezolid is used in patients receiving an SSRI. Other antibiotic
      options should be considered first, and linezolid should be reserved as the last
      resort if possible. If the infection requires linezolid, the SSRI should be
      discontinued, and the patient should be monitored closely for serotonin syndrome.

PMID- 16466334
TI  - Nesiritide therapy in a term neonate with renal disease.
AB  - A term (39-wk-old) male neonate exhibited respiratory distress and anuria within
      2 days of birth. The patient was diagnosed with pulmonary hypertension,
      polycystic kidney disease, and heart failure; his initial B-type natriuretic
      peptide concentration was 2460 pg/ml. After minimal response to loop diuretics,
      the patient was given an infusion of nesiritide 0.01 microg/kg/minute, with no
      loading dose. Urine output increased over 400%, and cardiac function improved.
      Nesiritide was titrated to 0.03 microg/kg/minute with no hypotension, decreased
      renal function, or adverse cardiac sequelae over the next 6 days. No subsequent
      changes in cardiac function occurred during the infant's stay in a progressive
      care unit, but he died at age 5.5 months due to sepsis. This case report
      demonstrates the successful first use of nesiritide therapy in a neonate with
      renal disease. Further studies are warranted to evaluate the safety and
      administration of this agent in the neonatal patient population.

PMID- 16466333
TI  - Administration of a large nesiritide bolus dose in a pediatric patient: case
      report and review of nesiritide use in pediatrics.
AB  - Nesiritide (recombinant B-type natriuretic peptide) is often given for
      symptomatic relief of acute decompensated heart failure in adults. The literature
      describing the safety or efficacy of nesiritide in children is minimal, and we
      know of no data that describe the effects of a nesiritide overdose in adults or
      children. A 3-year-old, 10.9-kg girl was admitted to the pediatric intensive care
      unit with the diagnosis of dilated cardiomyopathy and acute decompensated heart
      failure. She received several vasoactive infusions during her admission,
      including nesiritide. On hospital day 47 (day 45 of nesiritide therapy), the
      patient received an 18-fold overdose of nesiritide, with no hemodynamic, cardiac,
      or renal sequelae. She subsequently underwent successful cardiac transplantation.
      The nesiritide treatment duration was longer for this patient than the 45 days
      previously reported in a pediatric patient. No hemodynamic instability or cardiac
      or renal sequelae were associated with the large, inadvertent bolus in our
      patient. This case report demonstrates the lack of adverse events in a pediatric
      patient administered nesiritide beyond the recommended dosing parameters.
      Increased vigilance is always advised when administering drugs not commonly given
      to pediatric patients.

PMID- 16466335
TI  - Possible effect of thyroid function on anticoagulant response to unfractionated
      heparin.
AB  - Many factors are known to influence the unfractionated heparin (UFH) dosage
      required to achieve therapeutic anticoagulation, including weight, sex, age,
      tobacco smoking, and diabetes mellitus. However, no interaction between thyroid
      function and UFH has been documented. An 83-year-old Caucasian woman had active
      hyperthyroidism that appeared to significantly increase her dosage requirements
      for UFH. The patient had atrial fibrillation secondary to the hyperthyroidism.
      She had no known factors that would increase UFH requirements. A UHF dosage of
      1400 U/hour was needed to achieve a therapeutic level of anticoagulation
      (activated partial thromboplastin time 62 sec). After she was treated for
      hyperthyroidism, her atrial fibrillation resolved and UFH was discontinued. On
      day 9 of her hospital admission, atrial fibrillation resumed, and the patient's
      thyroid function began to normalize. Unfractionated heparin was restarted, and
      this time therapeutic anticoagulation was achieved with only 800 U/hour. This
      patient's experience suggests a previously undocumented and clinically
      significant relationship between active hyperthyroidism and altered dosage
      requirements for UFH. Recognition of this potential interaction may shorten the
      time required for patients with hyperthyroidism to achieve therapeutic
      anticoagulation, thereby preventing complications associated with subtherapeutic
      anticoagulation.

PMID- 16466336
TI  - Sirolimus-itraconazole interaction in a hematopoietic stem cell transplant
      recipient.
AB  - Interactions between azole antifungal agents and immunosuppressants that are
      metabolized by cytochrome P450 3A4 (chiefly calcineurin inhibitors) are well
      documented. Interactions between itraconazole and sirolimus are known to occur in
      patients after solid organ transplantation, but interactions in hematopoietic
      stem cell transplant (HSCT) recipients have yet to be reported in the literature.
      We describe an allogeneic HSCT recipient who experienced supratherapeutic trough
      levels of sirolimus as a result of its coadministration with itraconazole. This
      patient was a 20-year-old African-American man who underwent HSCT for treatment
      of myelodysplastic syndrome with severe aplastic anemia. After several regimen
      changes, the patient received oral itraconazole 200 mg every 12 hours and
      sirolimus at a dosage of 7 mg/day on days 76-80 and 5 mg/day on days 81 and 82.
      His sirolimus whole blood trough levels were 17.5 and 35.6 ng/ml on days 80 and
      82, respectively (therapeutic range 5-15 ng/ml). An interaction between
      itraconazole and sirolimus was suspected, and sirolimus was withheld on days 83
      90. On day 90, the patient's sirolimus trough level had normalized to 4.4 ng/ml.
      Sirolimus was resumed at 1-2 mg/day, with adjustments as needed to maintain
      trough levels of 10-15 ng/ml. Both the itraconazole and sirolimus were eventually
      were discontinued. The patient died, however, from a disseminated adenovirus
      infection leading to end-organ failure. Sirolimus is extremely sensitive to the
      inhibitory potential of azole antifungals. We propose that itraconazole also has
      a potent effect on sirolimus metabolism. Preemptive sirolimus dosage reduction
      and close monitoring of its whole blood trough levels are required whenever this
      combination is considered to avoid immunosuppressant toxicity in already
      critically ill patients.

PMID- 16466337
TI  - Not all intravenous immunoglobulins are the same: appropriate selection in
      patients with compromised renal function.

PMID- 16466338
TI  - Implementing a multidisease chronic care model in primary care using people and
      technology.
AB  - Management of chronic disease is performed inadequately in the United States in
      spite of the availability of beneficial, effective therapies. Successful programs
      to manage patients with these diseases must overcome multiple challenges,
      including the recognized fragmentation and complexity of the healthcare system,
      misaligned incentives, a focus on acute problems, and a lack of team-based care.
      In many successful programs, care is provided in settings or episodes that focus
      on a single disease. While these programs may allow for streamlined, focused
      provision of care, comprehensive care for multiple diseases may be more
      difficult. At Intermountain Healthcare (Intermountain), a generalist model of
      chronic disease management was formulated to overcome the limitations associated
      with specialization. In the Intermountain approach, which reflects elements of
      the Chronic Care Model (CCM), care managers located within multipayer primary
      care clinics collaborate with physicians, patients, and other members of a
      primary care team to improve patient outcomes for a variety of conditions. An
      important part of the intervention is widespread use of an electronic health
      record (EHR). This EHR provides flexible access to clinical data, individualized
      decision support designed to encourage best practice for patients with a variety
      of diseases (including co-occurring ones), and convenient communication between
      providers. This generalized model is used to treat diverse patients with
      disparate and coexisting chronic conditions. Early results from the application
      of this model show improved patient outcomes and improved physician productivity.
      Success factors, challenges, and obstacles in implementing the model are
      discussed.

PMID- 16466339
TI  - The metabolic syndrome: recognition and management.
AB  - The National Cholesterol Education Program defines the metabolic syndrome as
      three or more of five abnormalities: waist circumference of >40 in (102 cm) for
      men or >35 in (88 cm) for women, triglyceride level of > or =150 mg/dL, high
      density lipoprotein cholesterol of <40 mg/dL in men or <50 mg/dL in women, blood
      pressure of > or =130 or > or =85 mm Hg, and fasting glucose of > or =110 mg/dL.
      It is related to insulin resistance, but the two terms are not synonymous. Both
      are associated strongly with obesity. The metabolic syndrome is important as an
      indicator of increased risk of cardiovascular disease (CVD) in patients with and
      without clinical CVD. The CVD risk of the metabolic syndrome is greater than that
      conferred by any single CVD risk factor. Since risk factors tend to cluster, if
      one component of the metabolic syndrome is present, one should assess for other
      risk factors. The metabolic syndrome is also predictive of new-onset type 2
      diabetes. Early diagnosis provides justification for measures that can improve
      components of the syndrome and reduce CVD risk. The management strategy for
      metabolic syndrome focuses on overall CVD risk rather than single risk factors;
      effective therapy includes priority for weight reduction and increased physical
      activity. Pharmacotherapy is typically needed for control of high blood pressure,
      hypercoagulability, and increased levels of blood glucose and triglycerides.

PMID- 16466340
TI  - Evaluating the impact of a disease management program for chronic complex
      conditions at two large northeast health plans using a control group methodology.
AB  - The objective of this study was to observe trends in payer expenditures for plan
      members with one of 14 chronic, complex conditions comparing one group with a
      disease management program specific to their condition (the intervention group)
      and the other with no specific disease management program (the control group) for
      these conditions. The authors used payer claims and membership data to identify
      members eligible for the program in a 12-month baseline year (October 2001 to
      September 2002) and a subsequent 12-month program year (October 2002 to September
      2003). Two payers were analyzed: one health plan with members primarily in New
      Jersey (AmeriHealth New Jersey [AHNJ]), where the disease management program was
      offered, and one affiliated large plan with members primarily in the metro
      Philadelphia area, where the program was not offered. The claims payment policy
      for both plans is identical. Intervention and control groups were analyzed for
      equivalence. The analysis was conducted in both groups over identical time
      periods. The intervention group showed statistically significant (p < 0.01)
      differences in total paid claims trend and expenditures when compared to the
      control group. Intervention group members showed a reduction in expenditures of 
      8%, while control group members showed an increase of +10% over identical time
      periods. Subsequent analyses controlling for outliers and product lines served to
      confirm the overall results. The disease management program is likely responsible
      for the observed difference between the intervention and control group results. A
      well-designed, targeted disease management program offered by a motivated,
      supportive health plan can play an important role in cost improvement strategies
      for members with complex, chronic conditions.

PMID- 16466341
TI  - Population-based medical and disease management: an evaluation of cost and
      quality.
AB  - Reports by the Institute of Medicine and the Health Care Financing Administration
      have emphasized that the integration of medical care delivery, evidence-based
      medicine, and chronic care disease management may play a significant role in
      improving the quality of care and reducing medical care costs. The specific aim
      of this project is to assess the impact of an integrated set of care coordination
      tools and chronic disease management interventions on utilization, cost, and
      quality of care for a population of beneficiaries who have complementary health
      coverage through a plan designed to apply proactive medical and disease
      management processes. The utilization of health care services by the study
      population was compared to another population from the same geographic service
      area and covered by a traditional fee-for-service indemnity insurance plan that
      provided few medical or disease management services. Evaluation of the difference
      in utilization was based on the difference in the cost per-member-per-month
      (PMPM) in a 1-year measurement period, after adjusting for differences in fee
      schedules, case-mix and healthcare benefit design. After adjustments for both
      case-mix and benefit differences, the study group is $63 PMPM less costly than
      the comparison population for all members. Cost differences are largest in the 55
      64 and 65 and above age groups. The study group is $115 PMPM lower than the
      comparison population for the age category of 65 years and older, after
      adjustments for case-mix and benefits. Health Plan Employer and Data Information
      Set (HEDIS)-based quality outcomes are near the 90th percentile for most
      indications. The cost outcomes of a population served by proactive, population
      based disease management and complex care management, compared to an unmanaged
      population, demonstrates the potential of coordinated medical and disease
      management programs. Further studies utilizing appropriate methodologies would be
      beneficial.

PMID- 16466342
TI  - Clinical features of high-risk older persons identified by predictive modeling.
AB  - The objective of this study was to describe the clinical features of older
      persons identified as high risk by a predictive modeling algorithm and to
      determine their suitability for clinical interventions like case management or
      disease management. A cross-sectional survey was undertaken at a community-based
      general internal medicine practice with 826 older patients enrolled in a Medicare
      like health plan for military retirees and their dependents. Administrative
      claims data provided information about all 826 enrollees' chronic conditions,
      their use of health services, and the cost of those services during the past
      year. A survey mailed to 150 identified high-risk enrollees provided information
      about sociodemographic characteristics, general health, bed disability days,
      restricted activity days, activities of daily living (ADL) limitations, and
      instrumental activities of daily living (IADL) limitations. Compared to the 676
      low-risk enrollees, the 150 high-risk enrollees had higher prevalence of eight
      individual chronic conditions, higher total chronic conditions (2.93 vs. 1.48, p
      < 0.001), higher annual rates of hospital admission (1.1 vs. 0.1, p < 0.001),
      more annual hospital days (7.3 vs. 0.5, p < 0.001), and higher total health
      insurance expenditures ($22,815 vs. $3,726, p < 0.001). The high-risk respondents
      to the survey (response rate = 80.0%) had suboptimal health (42.8% "fair or
      poor"), impaired functional ability (36.3% with 1+ ADL limitations, 58.1% with 1+
      IADL limitations), and frequent health-related disruptions in their activities
      during the previous six months (38.7% with 1+ bed disability day, 52.3% with 1+
      restricted activity day). A claims-based predictive modeling algorithm identifies
      older persons whose health, functional ability, and use of health services
      suggest they are good candidates for clinical interventions such as case
      management and disease management.

PMID- 16466343
TI  - Increased continuity of care associated with decreased hospital care and
      emergency department visits for patients with asthma.
AB  - The objective of this study was to determine the association between continuity
      of care and emergency room visits/hospital care for patients with asthma. A
      population-based study was conducted using administrative healthcare datasets
      obtained from Alberta Health and Wellness, Alberta, Canada. The 4-year study
      period extended from April 1, 1996 to March 31, 2000, and took place at the
      Palliser Health Region in Alberta, Canada, which has a population of 88,000
      people. A population-based sample of 2774 patients, diagnosed with asthma between
      ages 5 and 45 with two or more office visits for asthma and who lived in the
      Palliser Health Region for 2 consecutive years during the study period, was
      studied. The main outcome measure was the association of continuity of care with
      hospitalizations and emergency room visits for patients with asthma. Continuity
      of care was the proportion of total physician visits made to the most frequently
      visited physician. High continuity of care was associated with a decreased risk
      of an emergency visit (OR = 0.24: 95% CI 0.19-0.29), number of emergency visits
      (RR = 0.37; 95% CI 0.32-0.42), decreased risk of number of hospitalizations (RR =
      0.69; 95% CI 0.54-0.89), and total days in hospital (average difference = 0.77;
      95% CI 0.63-0.95), but not with ever hospitalized. High continuity of care was
      associated with a 60%-75% reduction in emergency room visits and an approximate
      25% reduction in number of hospitalizations in patients with asthma.
      Interventions to improve continuity of care could have the potential to improve
      care and reduce cost.

PMID- 16466344
TI  - Folate synthesis in plants: purification, kinetic properties, and inhibition of
      aminodeoxychorismate synthase.
AB  - pABA (p-aminobenzoate) is a precursor of folates and, besides esterification to
      glucose, has no other known metabolic fate in plants. It is synthesized in two
      steps from chorismate and glutamine, the first step being their conversion into
      glutamate and ADC (4-aminodeoxychorismate). In Escherichia coli, two proteins
      forming a heterodimeric complex are required for this reaction, but, in plants
      and lower eukaryotes, a single protein is involved. The Arabidopsis enzyme was
      expressed in E. coli and was purified to homogeneity. The monomeric enzyme (95
      kDa) catalyses two reactions: release of NH3 from glutamine (glutaminase
      activity) and substitution of NH3 for the hydroxy group at position 4 of
      chorismate (ADC synthase activity). The kinetic parameters of the plant enzyme
      are broadly similar to those of the bacterial complex, with K(m) values for
      glutamine and chorismate of 600 and 1.5 microM respectively. As with the
      bacterial enzyme, externally added NH3 was a very poor substrate for the plant
      enzyme, suggesting that NH3 released from glutamine is preferentially channelled
      to chorismate. The glutaminase activity could operate alone, but the presence of
      chorismate increased the efficiency of the reaction 10-fold, showing the
      interdependency of the two domains. The plant enzyme was inhibited by
      dihydrofolate and its analogue methotrexate, a feature never reported for the
      prokaryotic system. These molecules were inhibitors of the glutaminase reaction,
      competitive with respect to glutamine (K(i) values of 10 and 1 microM for
      dihydrofolate and methotrexate respectively). These findings support the view
      that the monomeric ADC synthase is a potential target for antifolate drugs.

PMID- 16466346
TI  - Increased levels of tumour necrosis factor-alpha (TNF-alpha) in patients with
      Type II diabetes mellitus after myocardial infarction are related to endothelial
      dysfunction.
AB  - The pathophysiology of insulin resistance and atherosclerosis may share a common
      inflammatory basis, maintaining endothelial dysfunction, suggesting why patients
      with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI
      (myocardial infarction), but it remains unclear how these parameters are inter
      related. Forty patients with an MI (20 patients with and 20 patients without
      T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow
      mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation
      (determined by ultrasound), S(I) (insulin sensitivity index; determined by
      isoglycaemic-hyperinsulinaemic clamp) and serum levels of CRP (C-reactive
      protein), TNF-alpha (tumour necrosis factor-alpha), IL-6 (interleukin 6),
      resistin and adiponectin (determined by ELISA) were measured. Associations
      between FMD/NTG and S(I), and CRP, TNF-alpha, IL-6, adiponectin, resistin,
      lipids, blood pressure, BMI (body mass index) and brachial artery diameter were
      then assessed. FMD (2.1 compared with 4.7%; P<0.05), NTG (14.9 compared with
      21.2%; P<0.05) and S(I) [4.3 compared with 6.6 10(-4) dl.kg(-1) of body
      weight.min(-1).(mu-units/ml)(-1); P<0.05], and adiponectin levels (3.1 compared
      with 6.4 microg/ml; P<0.01) were all lower in patients with T2DM. TNF-alpha (6.9
      compared with 1.8 pg/ml; P<0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P<0.01)
      levels were higher in patients with T2DM, whereas differences in CRP and resistin
      levels did not attain statistical significance between the two groups. TNF-alpha
      concentrations and brachial artery diameter were negatively, whereas S(I) was
      positively, correlated with FMD. Adjustment for age weakened the association for
      S(I), whereas TNF-alpha and brachial artery diameter remained significantly
      associated with FMD after adjustment for group, age and BMI. Endothelial
      dysfunction and low-grade inflammation co-exist in T2DM after MI. These results
      suggest that the endothelium is negatively impacted in multiple ways by the
      diabetic state after an MI.

PMID- 16466345
TI  - Mitochondria maintain maturation and secretion of lipoprotein lipase in the
      endoplasmic reticulum.
AB  - Considering the physiological Ca2+ dynamics within the ER (endoplasmic
      reticulum), it remains unclear how efficient protein folding is maintained in
      living cells. Thus, utilizing the strictly folding-dependent activity and
      secretion of LPL (lipoprotein lipase), we evaluated the impact of ER Ca2+ content
      and mitochondrial contribution to Ca2+-dependent protein folding. Exhaustive ER
      Ca2+ depletion by inhibition of sarcoplasmic/endoplasmic reticulum Ca2+-ATPases
      caused strong, but reversible, reduction of cell-associated and released activity
      of constitutive and adenovirus-encoded human LPL in CHO-K1 (Chinese-hamster ovary
      K1) and endothelial cells respectively, which was not due to decline of mRNA or
      intracellular protein levels. In contrast, stimulation with the IP3 (inositol
      1,4,5-trisphosphate)-generating agonist histamine only moderately and transiently
      affected LPL maturation in endothelial cells that paralleled a basically
      preserved ER Ca2+ content. However, in the absence of extracellular Ca2+ or upon
      prevention of transmitochondrial Ca2+ flux, LPL maturation discontinued upon
      histamine stimulation. Collectively, these data indicate that Ca2+-dependent
      protein folding in the ER is predominantly controlled by intraluminal Ca2+ and is
      largely maintained during physiological cell stimulation owing to efficient ER
      Ca2+ refilling. Since Ca2+ entry and mitochondrial Ca2+ homoeostasis are crucial
      for continuous Ca2+-dependent protein maturation in the ER, their pathological
      alterations may result in dysfunctional protein folding.

PMID- 16466347
TI  - My sister's breast cancer.

PMID- 16466348
TI  - The reliability and validity of birth certificates.
AB  - OBJECTIVES: To summarize the reliability and validity of birth certificate
      variables and encourage nurses to spearhead data improvement. DATA SOURCES: A
      Medline key word search of reliability and validity of birth certificate, and a
      reference review of more than 60 articles were done. STUDY SELECTION: Twenty-four
      primary research studies of U.S. birth certificates that involved validity or
      reliability assessment. DATA EXTRACTION: Studies were reviewed, critiqued, and
      organized as either a reliability or a validity study and then grouped by birth
      certificate variable. DATA SYNTHESIS: The reliability and validity of birth
      certificate data vary considerably by item. Insurance, birthweight, Apgar score,
      and delivery method are more reliable than prenatal visits, care, and maternal
      complications. Tobacco and alcohol use, obstetric procedures, and delivery events
      are unreliable. Birth certificates are not valid sources of information on
      tobacco and alcohol use, prenatal care, maternal risk, pregnancy complications,
      labor, and delivery. CONCLUSIONS: Birth certificates are a key data source for
      identifying causes of increasing U.S. infant mortality but have serious
      reliability and validity problems. Nurses are with mothers and infants at birth,
      so they are in a unique position to improve data quality and spread the word
      about the importance of reliable and valid data. Recommendations to improve data
      are presented.

PMID- 16466349
TI  - Lesbian experiences and needs during childbirth: guidance for health care
      providers.
AB  - OBJECTIVE: To provide an overview of the literature regarding lesbian experiences
      of childbirth and to offer health care providers guidance in supporting the
      childbearing lesbian couple. DATA SOURCES: A search of the literature from 1980
      through 2004 was conducted using PsycINFO, Ovid, PubMed, Ebscohost, and Cinahl,
      and the key words, lesbian, childbirth, parenting health care providers,
      pregnancy, artificial insemination, parental rights. DATA EXTRACTION: A critical
      review of all articles from relevant journals was included with attention to the
      needs of lesbian women concerning childbirth and implications for health care
      provider care. DATA SYNTHESIS: The four areas of concern identified for lesbians
      considering parenting were (a) the pros and cons of disclosing sexual orientation
      to caregivers and finding lesbian-sensitive caregivers, (b) the options available
      when deciding how to conceive, (c) assurance of the desired level of partner
      involvement, and (d) the legal considerations for the conception process and for
      the protection of both parents as well as the child. Methods and strategies to
      assist health care providers to meet the needs of lesbian clients were gleaned
      from the literature. CONCLUSION: A growing numbers of lesbian women are becoming
      consumers of childbirth health care. Health care outcomes of lesbian women and
      their infants are affected by experiences during pregnancy and childbirth and by
      the attitudes and actions of health care providers. Evidence exists that health
      care outcomes for lesbians are improved when health care providers are
      knowledgeable about and sensitive to the unique needs of lesbian clients.

PMID- 16466350
TI  - Vaginal douching practices of women in eight Florida panhandle counties.
AB  - OBJECTIVE: To document knowledge, beliefs, douching practices, prevalence of
      bacterial vaginosis, and preterm births in women who douche. DESIGN: Descriptive,
      cross-sectional nonexperimental design. SETTING: Six private midwifery/nurse
      practitioner offices and eight county health departments in the Florida
      panhandle. PARTICIPANTS: Four hundred eighty-three English- or Spanish-speaking
      women aged 14 to 45 years. METHODS: Self-administered questionnaire about
      douching; medical record review. MAIN OUTCOME MEASURES: Prevalence of douching,
      history of preterm labor, preterm births, and prevalence of bacterial vaginosis.
      RESULTS: Of 483 women, 76% had douched, 43% douched at least once per month, and
      36% were unaware they should not douche. As determined by odds ratio, women who
      douched monthly were 2.5 times more likely to have a history of bacterial
      vaginosis than women who did not douche (p < .001), and women who douched weekly
      were 2.75 times more likely to have bacterial vaginosis (p = .004). Of 409
      clients with medical records available, 32 had preterm births of which 69% had a
      history of bacterial vaginosis (x2 = 4.5, df = 1, p = .034). Among women with
      preterm births who douched regularly prior to pregnancy (n = 14), 87% had a
      history of bacterial vaginosis (x2 = 7.14, df = 1, p = .008). CONCLUSIONS:
      Associations of douching with bacterial vaginosis and bacterial vaginosis with
      preterm labor were significant. Health care professionals should initiate
      discussions to discourage douching.

PMID- 16466352
TI  - Fathers' support to mothers of medically fragile infants.
AB  - OBJECTIVE: To examine mothers' perceptions of support from fathers over the 1st
      year after birth of a medically fragile infant. DESIGN: A descriptive,
      correlation design based on an ecologic systems view of the family. It was
      hypothesized that the levels of paternal support would be influenced by factors
      within the two subsystems: the mother-father system (marital status) and the
      child subsystem (health and gender). SETTING: A tertiary care children's
      hospital. PARTICIPANTS: Sixty-four mothers of medically fragile term and preterm
      infants, who were married or living with the father. MAIN OUTCOME MEASURES: The
      Stress Support Scale assessed maternal perceptions of helpfulness and
      satisfaction with paternal support at enrollment, after discharge, and around 1
      year of age. RESULTS: Mothers reported high levels of help from fathers at
      enrollment. Married mothers did not differ from unmarried mothers in their
      perceptions of helpfulness of support but were more satisfied with support.
      Mothers of female infants received more help from fathers than mothers of male
      infants, and this difference increased over time. However, mothers of female
      infants were not more satisfied with paternal support. Neither number of
      technologies nor birthweight related the maternal perceptions of paternal
      support. CONCLUSIONS: Family systems factors were more significant in maternal
      perceptions of paternal support than the health status of the infant.

PMID- 16466351
TI  - Validity and reliability of the Perceived Readiness for Discharge After Birth
      Scale.
AB  - OBJECTIVE: To assess the psychometric properties of a scale measuring mothers'
      perceptions of readiness for discharge after birth. DESIGN: Psychometric analyses
      including construct validity using factor analysis and known groups comparisons,
      predictive validity, and reliability. Data were collected at discharge and 6
      weeks postdischarge. SETTING: Tertiary-level perinatal center in the Midwestern
      United States. PARTICIPANTS: 1,462 postpartum mothers. INTERVENTION: None. MAIN
      OUTCOME MEASURES: Perceived Readiness for Discharge After Birth Scale scores;
      subscale scores for personal status and knowledge factors. RESULTS: Exploratory
      and confirmatory factor analyses indicated that the scale contained two factors.
      Perceived Readiness for Discharge After Birth Scale scores were lower for mothers
      who were breastfeeding, married, primiparous, and had a short hospital stay (less
      than 30 hours) than for their comparison groups. The Perceived Readiness for
      Discharge After Birth Scale personal status factor was predictive of self
      reported physical and psychosocial problems and unscheduled utilization of health
      services in the first 6 weeks postpartum. The knowledge factor was predictive of
      postdischarge telephone calls to the pediatric provider. Reliability estimates
      ranged from 0.83 to 0.89 for the total scale and subscales. CONCLUSIONS: The
      Perceived Readiness for Discharge After Birth Scale performed well in
      psychometric testing. Assessing mothers' perceptions of readiness for discharge
      is important for measuring outcomes of hospitalization and for identifying
      mothers at risk for postdischarge problems.

PMID- 16466353
TI  - Perinatal violence assessment: teenagers' rationale for denying violence when
      asked.
AB  - OBJECTIVE: To describe teenagers' experiences with perinatal violence assessment.
      DESIGN: A descriptive design utilizing qualitative content analysis. SETTING:
      Participants were recruited from gynecologic clinics of two level III maternity
      units and interviewed offsite. PARTICIPANTS: Twenty nonpregnant teenagers between
      the ages of 18 and 20 years who had experienced physical or sexual abuse in the
      year before or during (or both) a pregnancy occurring within the last 3 years
      were recruited for this study, regardless of past pregnancy outcome. METHODS:
      Data were analyzed using categorical content analysis. RESULTS: Participants
      reported a range of violence experiences from their parents, current and past
      intimate partners, and gangs (groups). Four categories emerged that addressed
      their reasons for not disclosing violence to their health care providers:
      Power/Powerlessness, Fear/Hope, Trust/Mistrust, and Action/Inertia. CONCLUSIONS:
      Abused teenagers have unique needs and concerns that should be addressed when
      providing pregnancy care.

PMID- 16466355
TI  - Fathers' perspectives during pregnancy, postperinatal loss.
AB  - OBJECTIVE: To present information about the father's perspective during the
      experience of a pregnancy following perinatal loss. DESIGN: Descriptive
      phenomenology. SETTING: Interviews were done in a venue chosen by fathers (home,
      clinic). PARTICIPANTS: Ten fathers who had experienced a loss within the prior
      year and were currently with that partner in a subsequent pregnancy. FOUR THEMES
      EMERGED: Recognition, preoccupation, stoicism, and support. CONCLUSIONS:
      Participants describe the need to be recognized by others. The orderly conduct of
      their daily lives is disrupted by preoccupation with the pregnancy. They feel
      unable to share their own anxiety and fear because they want to protect the
      mothers. Societal pressure to "be strong" and the belief that "men don't share"
      appear to inhibit fathers from getting support. Strategies to assess and support
      fathers emotionally at the time of loss and in the subsequent pregnancy need to
      be explored.

PMID- 16466354
TI  - Psychosocial and spiritual factors associated with smoking and substance use
      during pregnancy in African American and White low-income women.
AB  - OBJECTIVE: To determine the associations between sociodemographic, psychosocial,
      and spiritual factors to health risk behaviors during pregnancy in African
      American and White low-income women. DESIGN: Descriptive, using prenatal
      interviews and medical record review as data sources. SETTING: An urban prenatal
      clinic in the Midwestern United States. PARTICIPANTS: One hundred thirty
      ethnically diverse low-income women. MAIN OUTCOME MEASURES: Smoking and substance
      use in pregnancy. RESULTS: For the total sample, 39% reported smoking and 28%
      reported substance use in pregnancy. Significant predictors of smoking were White
      race, less than high school education, abuse, and religiosity. Abuse and
      depressive symptoms predicted substance use. African American women were
      significantly less likely to report smoking in pregnancy (28%) than were White
      women (55%) (p < .05). African American women who smoked during pregnancy were
      significantly more likely to report lower levels of education (p < .01), less
      social support from others (p < .01) and total social support (p < .01), higher
      levels of stress (p < .05), and more frequent substance use (56.5%) than African
      American women who did not smoke (12%) (p < .001). White women who used
      substances were significantly more likely to report smoking (p < .01), abuse (p <
      .05), and a history of delivering a preterm or low-birthweight infant (p < .01)
      than the White women who did not. CONCLUSION: Integrating social support and
      stress-relieving activities in smoking cessation interventions, particularly for
      African American women, may reduce health risk behaviors, eliminate health
      disparities, and improve maternal and infant quality of life.

PMID- 16466356
TI  - The relationship between vulnerability factors and breastfeeding outcome.
AB  - OBJECTIVE: To determine whether vulnerability factors (confidence with
      breastfeeding, postpartum depression, supplementation, and perceived adequacy of
      support) are associated with breastfeeding outcome at 6 weeks postpartum after
      controlling for age and education. DESIGN: Secondary analysis of a cross
      sectional telephone survey at 6 weeks postpartum. SETTING: Ottawa-Carleton,
      Ontario, Canada. PARTICIPANTS: A proportionate, consecutive sample of
      breastfeeding women from each of four hospitals in the region (526/554, 95%
      response rate). METHODS: Stratified bivariate analyses were used to examine the
      relationship between each factor and breastfeeding outcome. Multivariate logistic
      regression analyses examined relationships between all factors and breastfeeding
      outcome. RESULTS: In the logistic regression analyses, confidence with
      breastfeeding (odds ratio: 1.85, 95% confidence interval: 1.50-2.27, p < .001)
      and postpartum depression (odds ratio: 0.28, 95% confidence interval: 0.11-0.71,
      p= .007) were related to breastfeeding after controlling for age and education.
      CONCLUSIONS: Support for breastfeeding should include assessment of maternal
      confidence with breastfeeding and postpartum depression. Evaluation of
      intervention strategies to address these vulnerability factors is a priority.

PMID- 16466358
TI  - A quasi-experimental trial on individualized, developmentally supportive family
      centered care.
AB  - OBJECTIVE: To evaluate the impact of individualized, developmentally supportive
      family-centered care on infant physiological variables, growth, behavioral stress
      cues, return to sleep state, medical and developmental progress, complications,
      resource utilization, parental perception of the neonatal intensive-care unit
      experience, and overall parental satisfaction. DESIGN: Quasi-experimental,
      repeated measures design. SETTING: Developmental and a control nursery in a 78
      bed, level II/III neonatal intensive-care unit. PARTICIPANTS: A convenience
      sample of 114 premature infants and their parents. INTERVENTIONS: Control group
      infants received the routine neonatal intensive-care unit standard of care.
      Experimental infants received routine care plus the addition of individualized,
      developmentally supportive family-centered interventions. MAIN OUTCOME MEASURES:
      Between groups, there were no statistically significant differences in
      demographic factors, days to medical or developmental milestones, length of stay,
      or direct cost/case. Repeated measures analysis of variance determined that at
      every point of data collection, the average number of baseline, activity, and
      postactivity stress cues were lower in the developmentally supportive group.
      Infants in the developmental group had 8% less sedatives/narcotics and 15% less
      vasopressors costs than the control group. There were no differences in
      complication rates, parental perceptions of the neonatal intensive-care unit
      experience, or parental satisfaction between groups. CONCLUSIONS: Preterm infants
      who received developmentally supportive family-centered care demonstrated fewer
      behavioral stress cues and comparable short-term outcomes and resource
      utilization than infants who received routine care.

PMID- 16466357
TI  - Immigrant Asian Indian women and postpartum depression.
AB  - OBJECTIVE: To determine the incidence of postpartum depressive symptomatology in
      a sample of immigrant Asian Indian women and to establish whether cultural
      factors such as arranged marriage or gender of the newborn are associated with
      differences in depression scores. DESIGN: Quantitative, descriptive study.
      SETTING: Ten private obstetric and pediatric offices in Northern California.
      PARTICIPANTS: A convenience sample of 58 self-selected immigrant Asian Indian
      women between 2 weeks and 12 months postpartum. MAIN OUTCOME MEASURE: Depressive
      symptomatology as measured by the 35-item self-report Postpartum Depression
      Screening Scale. RESULTS: There was a minor depressive symptomatology rate of 28%
      and an additional major depressive symptomatology rate of 24%. No differences in
      depression scores were found with regard to arranged marriage or the gender of
      the newborn. CONCLUSIONS: Findings suggest that Asian Indian women living in the
      United States are just as likely to experience postpartum depressive
      symptomatology as White women. Therefore, it is critical to identify and refer
      women at risk for postpartum depression to ensure they do not become part of the
      50% who remain undiagnosed. Health care providers need to become cognizant of the
      potential for postpartum depression and become skilled in the detection of this
      mood disorder.

PMID- 16466359
TI  - Fetal heart rate patterns and sudden infant death syndrome.
AB  - OBJECTIVE: To determine differences in electronic fetal monitoring patterns
      between infants who died of sudden infant death syndrome and controls. DESIGN:
      Case-control study (N = 127). SETTING: A tertiary-level women's hospital in
      Providence, Rhode Island. PARTICIPANTS: Infants born between 1990 and 1998 who
      subsequently died of sudden infant death syndrome and controls. Demographic and
      clinical data included medical maternal charts and fetal monitoring records.
      RESULTS: Compared with controls (n = 98), the mothers whose infants subsequently
      died of sudden infant death syndrome (n = 29) had lower birthweight babies
      (sudden infant death syndrome 2,840 vs. controls 3,385 g; p < .01), were younger
      (22 vs. 28 years; p < .01), were more likely to receive Medicaid health insurance
      (odds ratio 4.6; confidence interval 1.9-11.2), were more likely to be unmarried
      (odds ratio 5.2; confidence interval 2.1-12.8), had less intention to breastfeed
      (26% vs. 57%), and were more likely to smoke (odds ratio 4.6; confidence interval
      9-11.2). MAIN OUTCOME MEASURES: There were no statistical differences in fetal
      heart rate variability or sleep/wake cycles detected between groups. CONCLUSION:
      Statistical differences were found in demographic characteristics between sudden
      infant death syndrome mother-infant couples and their controls. However, no
      differences were detected in the intrapartum electronic fetal monitoring records,
      specifically in variability and sleep/wake cycles.

PMID- 16466362
TI  - Information technology update.

PMID- 16466360
TI  - Umbilical cord care: a pilot study comparing topical human milk, povidone-iodine,
      and dry care.
AB  - OBJECTIVE: To compare the incidence of omphalitis among three groups, each using
      a different type of newborn cord care: povidone-iodine, dry care, and topical
      human milk. DESIGN: Case control. SETTING: A large urban university hospital in
      Turkey and participant homes after discharge. PARTICIPANTS: 150 healthy, full
      term newborns and their mothers. INTERVENTIONS: Umbilical cord care consisted of
      one of three methods: topical application of povidone-iodine twice daily, topical
      application of mother's milk twice daily, or dry care (keeping the cord dry and
      clean). MAIN OUTCOME MEASURE: Outcome was measured in terms of the presence or
      absence of omphalitis and the number of days elapsed before cord separation. An
      ongoing questionnaire was administered by telephone every other day after the
      participants left the hospital. In addition to demographic information, the cord
      separation day and any signs of omphalitis were recorded in the questionnaire.
      RESULTS: There were no significant differences between the three groups in terms
      of omphalitis occurrence. Two cases of omphalitis were observed (one in the human
      milk group, one in the povidone-iodine group). Interestingly, babies in the dry
      care or topical human milk group had shorter cord separation times than those in
      the povidone-iodine group. CONCLUSION: The cultural practice of applying human
      milk to the umbilical cord stump appears to have no adverse effects and is
      associated with shorter cord separation times than are seen with the use of
      antiseptics.

PMID- 16466363
TI  - Implementing a perinatal clinical information system: a work in progress.
AB  - Implementation of a clinical information system is a work in progress. There are
      many factors to consider, including (a) clearly defining the scope of the project
      and associated goals, (b) identifying background, skills, and beliefs of the key
      players, (c) assessing the unit's strengths and weaknesses, (d) assessing the
      current documentation's strengths and weaknesses, (e) assessing the clinical
      information system's strengths and weaknesses, (f) determining the project's
      constraints, and (g) discussing different implementation strategies. This article
      describes how these factors were considered during implementation of a clinical
      information system in a labor and delivery unit.

PMID- 16466364
TI  - Women's health nursing in the context of the National Health Information
      Infrastructure.
AB  - Nurses must be prepared to participate in the evolving National Health
      Information Infrastructure and the changes that will consequently occur in health
      care practice and documentation. Informatics technologies will be used to develop
      electronic health records with integrated decision support features that will
      likely lead to enhanced health care quality and safety. This paper provides a
      summary of the National Health Information Infrastructure and highlights
      electronic health records and decision support systems within the context of
      evidence-based practice. Activities at the Columbia University School of Nursing
      designed to prepare nurses with the necessary informatics competencies to
      practice in a National Health Information Infrastructure-enabled health care
      system are described. Data are presented from electronic (personal digital
      assistant) encounter logs used in our Women's Health Nurse Practitioner program
      to support evidence-based advanced practice nursing care. Implications for
      nursing practice, education, and research in the evolving National Health
      Information Infrastructure are discussed.

PMID- 16466365
TI  - Women's use of the Internet: what nurses need to know.
AB  - Women increasingly access the Internet for health information and social support
      in managing health-related changes. Some women's use of the Internet has
      empowered them and created changes in nurse-patient relationships. Nurses and
      patients must have a mutually respectful open dialogue to develop individualized
      appropriate plans of care, and nurses should recognize that women who do not have
      Internet access may have different learning needs.

PMID- 16466366
TI  - Personal digital assistants, wireless computing, smart cards, and biometrics: a
      hardware update for clinical practice.
AB  - This paper introduces current and future information technology tools for health
      care with a focus on perinatal and women's health areas of nursing. The
      technologies include personal digital assistants, wireless computing, smart
      cards, biometrics, and storage cards. Strategies to incorporate these
      applications into practice are discussed.

PMID- 16466367
TI  - Incidence and clinical significance of anti-PF4/heparin antibodies of the IgG,
      IgM, and IgA class in 755 consecutive patient samples referred for diagnostic
      testing for heparin-induced thrombocytopenia.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is usually caused by anti
      platelet factor 4 (PF4)/heparin antibodies, leading to intravascular platelet
      activation. These antibodies can be detected by PF4/polyanion antigen assays or
      platelet activation assays. While antigen assays are very sensitive and recognize
      immunoglobulin (Ig)G, IgA, and IgM antibodies, the role of IgM and IgA HIT
      antibodies is debated. Platelet activation assays recognize IgG and are more
      specific for clinical HIT. METHODS: We analyzed sera from 755 consecutive
      patients referred for diagnostic testing for HIT using a PF4/heparin enzyme
      linked immunosorbent assay (ELISA) for IgG, IgA, and IgM and by the heparin
      induced platelet activation (HIPA) test. Clinical information was provided by the
      treating physicians. RESULTS: A total of 108 of 755 (14.3%) patients tested
      positive, 105 (13.9%) in the PF4/heparin IgG/A/M ELISA [28 (26.7%) only for
      IgM/A]; 53 (7.0%) sera were positive in the HIPA, of those 50 tested also
      positive in the ELISA. In 77 patients sufficient clinical information was
      provided. Available clinical information for 17 of the 28 patients who had only
      IgM and/or IgA detected showed plausible alternative (non-HIT) explanations in
      four of seven who had thromboembolic complications and in nine of 10 who had
      isolated HIT. CONCLUSION: Detection of IgG, IgM and IgA class antibodies by
      PF4/heparin ELISA yields a positive test result about twice as often as does a
      platelet activation assay, with only a minority of the additional patients
      detected likely having HIT. Thus, there is a potential for considerable over
      diagnosis of HIT by laboratories that utilize only an ELISA for diagnostic
      testing.

PMID- 16466368
TI  - Antiphospholipid antibodies may be a new prognostic parameter in aggressive non
      Hodgkin's lymphoma.
AB  - OBJECTIVES: Patients with malignancies have an increased prevalence of
      antiphospholipid antibodies (APA). The aim of this study was to determine the
      prevalence of IgG, IgM, and IgA anticardiolipin antibodies (aCL) and anti-beta-2
      glycoprotein I antibodies (anti-beta2-GPI) in patients with non-Hodgkin's
      lymphoma (NHL), and to investigate their clinical and prognostic significance.
      METHODS: The study group included 86 patients with NHL. Enzyme-linked
      immunosorbent assay kits were used to measure the concentrations of aCL and anti
      beta2-GPI, and coagulation tests, to measure lupus anticoagulant (LAC) activity.
      Blood was collected at diagnosis in all patients and at follow-up in 15. Median
      follow-up time was 1.9 yr. RESULTS: Elevated APA levels were found in 35 patients
      (41%) at diagnosis: one patient aCL IgG, five patients aCL IgM, five aCL IgA, one
      anti-beta2-GPI IgG, 14 anti-beta2-GPI IgM, and 19 anti-beta2-GPI IgA; LAC
      activity was found in three of 67 patients (4.5%). There was no significant
      correlation between elevated APA levels and patient's age or sex, disease stage
      or grade, bone marrow involvement, B symptoms, serum lactate dehydrogenase
      levels, serum beta2 microglobulin levels, International Prognostic Index (IPI)
      score, performance status, type of treatment, or response to treatment. There was
      a correlation between elevated APA and absence of extranodal disease (P = 0.045).
      A strong negative correlation was found between elevated APA at diagnosis and
      survival time. Two-year survival was 90 +/- 5% for patients without APA at
      diagnosis compared with 63 +/- 11% for patients with an elevated APA levels (P =
      0.0025). APA added to the predictive value of IPI for event-free and overall
      survival. CONCLUSIONS: APA are elevated in 41% of NHL patients at diagnosis and
      are correlated with shortened survival. Their level may serve as an independent
      prognostic variable in aggressive NHL.

PMID- 16466373
TI  - New directions and interactions in metagenomics research.
AB  - Metagenomics, which aims to access the genomic potential of an environmental
      sample directly, is a burgeoning area that is generating enormous amounts of
      biological information. An examination of recent metagenomics literature reveals
      the discipline to be heading in new and interesting directions, including the
      investigation of the normal flora of mammals, analysis of ancient genomes, and
      exploration of the distribution of novel pathways. In addition, the development
      of new bioinformatics approaches and tools is allowing innovative mining of both
      existing and new data. Finally, there are indications that the integration of
      metagenomics with complementary approaches in microbial ecology is beginning.

PMID- 16466374
TI  - How elevated pCO2 modifies total and metabolically active bacterial communities
      in the rhizosphere of two perennial grasses grown under field conditions.
AB  - The response of total (DNA-based analysis) and active (RNA-based analysis)
      bacterial communities to a pCO2 increase under field conditions was assessed
      using two perennial grasses: the nitrophilic Lolium perenne and the
      oligonitrophilic Molinia coerulea. PCR- and reverse transcriptase-PCR denaturing
      gradient gel electrophoresis analysis of 16S rRNA genes generated contrasting
      profiles. The pCO2 increase influenced mainly the active and root-associated
      component of the bacterial community. Bacterial groups responsive to the pCO2
      increase were identified by sequencing of corresponding denaturing gradient gel
      electrophoresis bands. About 50% of retrieved sequences were affiliated to
      Proteobacteria. Our data suggest that Actinobacteria in soil and Myxococcales
      (Deltaproteobacteria) in root are stimulated under elevated pCO2.

PMID- 16466375
TI  - Enrichment and genotypic diversity of phlD-containing fluorescent Pseudomonas
      spp. in two soils after a century of wheat and flax monoculture.
AB  - Fluorescent Pseudomonas spp. producing the antibiotic 2,4-diacetylphloroglucinol
      (2,4-DAPG) play a key role in the suppressiveness of some soils to take-all of
      wheat and other diseases caused by soilborne pathogens. Soils from side-by-side
      fields on the campus of North Dakota State University, Fargo, USA, which have
      undergone continuous wheat, continuous flax or crop rotation for over 100 years,
      were assayed for the presence of 2,4-DAPG producers. Flax and wheat monoculture,
      but not crop rotation, enriched for 2,4-DAPG producers, and population sizes of
      log 5.0 CFU g root(-1) or higher were detected in the rhizospheres of wheat and
      flax grown in the two monoculture soils. The composition of the genotypes
      enriched by the two crops differed. Four BOX-PCR genotypes (D, F, G, and J) and a
      new genotype (T) were detected among the 2,4-DAPG producers in the continuous
      flax soil, with F- and J-genotype isolates dominating (41 and 39% of the total,
      respectively). In contrast, two genotypes (D and I) were detected in the soil
      with continuous wheat, with D-genotype isolates comprising 77% of the total. In
      the crop-rotation soil, populations of 2,4-DAPG producers generally were below
      the detection limit, and only one genotype (J) was detected. Under growth-chamber
      and field conditions, D and I genotypes (enriched by wheat monoculture) colonized
      the wheat rhizosphere significantly better than isolates of other genotypes,
      while a J-genotype isolate colonized wheat and flax rhizospheres to the same
      extent. This study suggests that, over many years of monoculture, the crop
      species grown in a field enriches for genotypes of 2,4-DAPG producers from the
      reservoir of genotypes naturally present in the soil that are especially adapted
      to colonizing the rhizosphere of the crop grown.

PMID- 16466376
TI  - Genetic diversity and biocontrol potential of fluorescent pseudomonads producing
      phloroglucinols and hydrogen cyanide from Swiss soils naturally suppressive or
      conducive to Thielaviopsis basicola-mediated black root rot of tobacco.
AB  - Pseudomonas populations producing the biocontrol compounds 2,4
      diacetylphloroglucinol (Phl) and hydrogen cyanide (HCN) were found in the
      rhizosphere of tobacco both in Swiss soils suppressive to Thielaviopsis basicola
      and in their conducive counterparts. In this study, a collection of Phl+
      HCN+Pseudomonas isolates from two suppressive and two conducive soils were used
      to assess whether suppressiveness could be linked to soil-specific properties of
      individual pseudomonads. The isolates were compared based on restriction analysis
      of the biocontrol genes phlD and hcnBC, enterobacterial repetitive intergenic
      consensus (ERIC)-PCR profiling and their biocontrol ability. Restriction analyses
      of phlD and hcnBC yielded very concordant relationships between the strains, and
      suggested significant population differentiation occurring at the soil level,
      regardless of soil suppressiveness status. This was corroborated by high strain
      diversity (ERIC-PCR) within each of the four soils and among isolates harboring
      the same phlD or hcnBC alleles. No correlation was found between the origin of
      the isolates and their biocontrol activity in vitro and in planta. Significant
      differences in T. basicola inhibition were however evidenced between the isolates
      when they were grouped according to their biocontrol alleles. Moreover, two main
      Pseudomonas lineages differing by the capacity to produce pyoluteorin were
      evidenced in the collection. Thus, Phl+ HCN+ pseudomonads from suppressive soils
      were not markedly different from those from nearby conducive soils. Therefore, as
      far as biocontrol pseudomonads are concerned, this work yields the hypothesis
      that the suppressiveness of Swiss soils may rely on the differential effects of
      environmental factors on the expression of key biocontrol genes in pseudomonads
      rather than differences in population structure of biocontrol Pseudomonas
      subcommunities or the biocontrol potential of individual Phl+ HCN+ pseudomonad
      strains.

PMID- 16466377
TI  - Cyanobacterial chemotaxis to extracts of host and nonhost plants.
AB  - Chemotaxis may be important when forming cyanobacterial symbioses. However,
      knowledge of cyanobacterial attraction towards plants and factors affecting
      chemotaxis is limited. Chemo-attraction was observed in Nostoc strains 8964:3 and
      PCC 73102 towards exudate or crushed extract of the natural hosts Gunnera
      manicata, Cycas revoluta and Blasia pusilla, and the nonhost plants Trifolium
      repens, Arabidopsis thaliana and Oryza sativa. As all tested plant extracts
      generated chemotaxis, the possibility to attract cyanobacteria may be widespread
      in plants. Chemotaxis was reduced by increased temperature and darkness and was
      stimulated by phosphorous and iron starvation and elevated salt concentration.
      Sugars (arabinose, galactose, and glucose) had a positive effect on chemotaxis,
      whereas flavonoids (chrysin and naringenin) and amino acids (methionine, glycine,
      serine, phenylalanine, glutamine, and lysine) had no effect.

PMID- 16466378
TI  - Characterization of cyanobacterial glnA gene diversity and gene expression in
      marine environments.
AB  - PCR primers were designed and used to amplify glnA, the gene that encodes
      glutamine synthetase, from pure cultures of cyanobacteria and four samples from
      different marine environments. The glnA phylogeny was similar to that of the 16S
      rRNA gene, indicating that glnA gene sequences can be used to identify
      cyanobacteria expressing the glnA gene. Diverse unicellular cyanobacteria glnA
      genes were recovered from the North Pacific Subtropical Gyre, Monterey Bay,
      Chesapeake Bay and waters off the New Jersey coast. The majority of sequences
      were closely related to sequences from Synechococcus strains (78-88% identical
      DNA sequences). A few sequences that clustered with Prochlorococcus glnA genes
      were recovered from Monterey Bay and the North Pacific Subtropical Gyre. The
      expression of glnA was assayed by reverse transcriptase PCR to determine if there
      was a daily pattern in gene expression of samples collected from New Jersey's
      Longterm Environmental Observatory site (LEO-15). glnA expression varied over the
      day, with different glnA sequence types exhibiting different daily cycles.
      Results showed that the glnA gene can be used to characterize the diversity of
      natural populations of cyanobacteria, and to characterize gene expression
      patterns of individual species or strains.

PMID- 16466379
TI  - Eukaryotic picoplankton communities of the Mediterranean Sea in summer assessed
      by molecular approaches (DGGE, TTGE, QPCR).
AB  - The composition and abundance of eukaryotic picoplankton (defined here as cells
      smaller than 3 mum) was investigated in the Morocco upwelling and throughout the
      Mediterranean Sea in late summer using flow cytometry and molecular methods
      (gradient gel electrophoresis and quantitative PCR). The picoplankton displayed
      characteristics typical of oligotrophic oceanic areas with concentrations down to
      1000 cells mL(-1) in the Eastern Basin. The most abundant eukaryotic sequences
      recovered by gradient gel electrophoresis were related to uncultivated marine
      groups: alveolates I (16%) and II (26%) and a newly discovered group (env Nansha,
      17%) for which sequences have been recently obtained from the South China Sea and
      that could be related to Acantharians. Prasinophyceae (photosynthetic green
      algae) accounted for 10% of the sequences, whereas Cercozoa, Stramenopiles,
      Polycystinea, dinoflagellates and ciliates provided minor contributions. The use
      of quantitative PCR coupled with taxon-specific primers allowed us to estimate
      the relative abundance of several taxa belonging to the Prasinophyceae. Of the
      three genera assessed, Bathycoccus appeared as the most abundant, forming
      localized maxima at depth.

PMID- 16466380
TI  - Synoptic determination of living/dead and active/dormant bacterial fractions in
      marine sediments.
AB  - The most widely used methods for the estimation of the living/dead fractions of
      bacterial cells involve specific stains that are able to reveal membrane
      integrity. Here, we have compared two different probes (propidium iodide and
      ethidium homodimer-2) that have different molecular weights and steric hindrance
      effects. We have also combined this method with the staining/destaining procedure
      that is currently used in the identification of potentially active cells. The
      procedure for marine sediments described here allows the synoptic (i.e. from the
      same filter) identification of: (i) the number of living bacteria; (ii) the
      number of active vs. dormant cells within this living fraction; (iii) the
      bacterial fraction with an intact nucleoid region without membrane integrity; and
      (iv) dead cells (devoid of the nucleoid region and without membrane integrity).
      Our results demonstrate that the concentration of propidium is crucial for the
      correct estimation of the dead bacterial fraction, ethidium homodimer-2 allows
      efficient and accurate estimates that are independent of the concentrations used
      and the sample storage. The active bacterial fraction represented c. 40% of the
      total bacterial abundance, the inactive/dormant fraction c. 30%, and the dead
      fraction was, on average, c. 30%. This method allows the processing of a large
      number of samples with high precision and at relatively low cost, and thus it
      provides additional synoptic insights into the metabolic state of bacteria in
      marine sediments.

PMID- 16466381
TI  - Effects of legacy nuclear waste on the compositional diversity and distributions
      of sulfate-reducing bacteria in a terrestrial subsurface aquifer.
AB  - The impact of legacy nuclear waste on the compositional diversity and
      distribution of sulfate-reducing bacteria in a heavily contaminated subsurface
      aquifer was examined. dsrAB clone libraries were constructed and restriction
      fragment length polymorphism (RFLP) analysis used to evaluate genetic variation
      between sampling wells. Principal component analysis identified nickel, nitrate,
      technetium, and organic carbon as the primary variables contributing to well-to
      well geochemical variability, although comparative sequence analysis showed the
      sulfate-reducing bacteria community structure to be consistent throughout
      contaminated and uncontaminated regions of the aquifer. Only 3% of recovered
      dsrAB gene sequences showed apparent membership to the Deltaproteobacteria. The
      remainder of recovered sequences may represent novel, deep-branching lineages
      that, to our knowledge, do not presently contain any cultivated members; although
      corresponding phylotypes have recently been reported from several different
      marine ecosystems. These findings imply resiliency and adaptability of sulfate
      reducing bacteria to extremes in environmental conditions, although the
      possibility for horizontal transfer of dsrAB is also discussed.

PMID- 16466382
TI  - Detection of activity among uncultured Actinobacteria in a drinking water
      reservoir.
AB  - The abundance, identity and activity of uncultured Bacteria and Actinobacteria
      present in a drinking water reservoir (North Pine Dam, Brisbane, Australia) were
      determined using a combination of fluorescence in situ hybridization (FISH) alone
      or with catalysed reporter deposition (CARD-FISH) with microautoradiography. The
      CARD-FISH technique was modified relative to previous described procedures and
      performed directly on gelatine cover slips in order to allow simultaneous
      combination with microautoradiography. Almost twofold higher numbers of
      microorganisms could be identified as either Bacteria or Actinobacteria using the
      CARD-FISH technique as compared with the traditional FISH technique. A
      combination of FISH or CARD-FISH with microautoradiography showed generally
      higher activity among the Actinobacteria than among all Bacteria. Another
      important observation was that many cells within the FISH-negative populations of
      both Actinobacteria and Bacteria were actively assimilating thymidine. Thus,
      great care should be taken when extrapolating the active fraction of a
      prokaryotic community to be equivalent to the FISH-detectable population in such
      environments. Bacterial groups within Actinobacteria produce the odours geosmin
      and 2-methylisoborneol, which lower the quality of surface water when used for
      drinking. The results indicate that combined microautoradiography and CARD-FISH
      may serve as an effective tool when studying identity and activity of
      microorganisms within freshwater environments.

PMID- 16466383
TI  - Survey of antibiotic resistance in an integrated marine aquaculture system under
      oxolinic acid treatment.
AB  - The consequences of antibiotic use in aquatic integrated systems, which are based
      on trophic interactions between different cultured organisms and physical
      continuity through water, need to be examined. In this study, fish reared in a
      prototype marine integrated system were given an oxolinic acid treatment, during
      and after which the level of resistance to this quinolone antibiotic was
      monitored among vibrio populations from the digestive tracts of treated fish, co
      cultured bivalves and sediments that were isolated on thiosulfate-citrate-bile
      sucrose. Oxolinic acid minimum inhibitory concentration distributions obtained
      from replica plating of thiosulfate-citrate-bile-sucrose plates indicated that a
      selection towards oxolinic acid resistance had occurred in the intestines of fish
      under treatment. In contrast, and despite oxolinic acid concentrations higher
      than minimum inhibitory concentrations of susceptible bacteria, no clear
      evolution of resistance levels was detected either in bivalves or in sediments.

PMID- 16466384
TI  - Stability and reproducibility of low-temperature anaerobic biological wastewater
      treatment.
AB  - The reproducibility of low-temperature anaerobic biological wastewater treatment
      trials was evaluated. Two identical anaerobic expanded granular sludge bed
      bioreactors were used to treat synthetic volatile fatty acid-based industrial
      wastewater under ambient conditions (18-20 degrees C) and to investigate the
      effect of various environmental perturbations on reactor performance and
      microbial community dynamics, which were assessed by chemical oxygen demand
      removal or effluent volatile fatty acid determination and terminal restriction
      fragment length polymorphism analysis, respectively. Methanogenic activity was
      monitored using specific methanogenic activity assays. Reactor performance and
      microbial community dynamics were each well replicated between Reactor 1 and
      Reactor 2. Archaeal dynamics, in particular, were associated with reactor
      operating parameters. Terminal restriction fragment length polymorphism data
      suggested dynamic acetoclastic and hydrogenophilic methanogenic populations and
      were in agreement with temporal specific methanogenic activity data. Putative
      psychrophilic populations were observed in anaerobic bioreactor sludge for the
      first time.

PMID- 16466386
TI  - Phylogeny of human intestinal bacteria that activate the dietary lignan
      secoisolariciresinol diglucoside.
AB  - The human intestinal microbiota is essential for the conversion of the dietary
      lignan secoisolariciresinol diglucoside (SDG) via secoisolariciresinol (SECO) to
      the enterolignans enterodiol (ED) and enterolactone (EL). However, knowledge of
      the species that catalyse the underlying reactions is scant. Therefore, we
      focused our attention on the identification of intestinal bacteria involved in
      the conversion of SDG. Strains of Bacteroides distasonis, Bacteroides fragilis,
      Bacteroides ovatus and Clostridium cocleatum, as well as the newly isolated
      strain Clostridium sp. SDG-Mt85-3Db, deglycosylated SDG. Demethylation of SECO
      was catalysed by strains of Butyribacterium methylotrophicum, Eubacterium
      callanderi, Eubacterium limosum and Peptostreptococcus productus. Dehydroxylation
      of SECO was catalysed by strains of Clostridium scindens and Eggerthella lenta.
      Finally, the newly isolated strain ED-Mt61/PYG-s6 catalysed the dehydrogenation
      of ED to EL. The results indicate that the activation of SDG involves
      phylogenetically diverse bacteria, most of which are members of the dominant
      human intestinal microbiota.

PMID- 16466385
TI  - Long-term monitoring of the succession of a microbial community in activated
      sludge from a circulation flush toilet as a closed system.
AB  - The microbial diversity and community succession of a circulation flush toilet
      were investigated by terminal restriction fragment length polymorphism and
      cloning analyses. Clonal libraries of 16S rRNA gene on day 3 and day 127 were
      constructed. On day 3, 102 clones were sequenced; Proteobacteria and
      Bacteroidetes accounted for 27% and 45%, respectively. On day 127, Proteobacteria
      had increased to 43% and Bacteroidetes had decreased to 26% of a total of 100
      clones. Terminal restriction fragment length polymorphism peaks were identified
      by in silico analysis of clone libraries. The relative abundances of Nitrosomonas
      increased from 1% to 6% with commencement of nitrification and denitrification.
      Similarly, the relative abundance of terminal restriction fragments generated
      from Xanthomonas increased from 3% to 10%. Therefore, these bacteria could play a
      prominent role in this process. To reveal the relationship between stability of
      the microbial community and performance of the system, microbial community
      succession was visualized by multidimensional scaling analysis. The microbial
      community structure changed markedly, particularly during the start-up period of
      the system. The plots then became stable after the start of nitrification and
      denitrification. This result suggests that the succession of microbial community
      structure had a correlation with the performance of the system.

PMID- 16466387
TI  - Metal resistance in Candida biofilms.
AB  - Yeasts are often successful in metal-polluted environments; therefore, the
      ability of biofilm and planktonic cell Candida tropicalis to endure metal
      toxicity was investigated. Fifteen water-soluble metal ions, chosen to represent
      groups 6A to 6B of the periodic table, were tested against this organism. With in
      vitro exposures as long as 24 h, biofilms were up to 65 times more tolerant to
      killing by metals than corresponding planktonic cultures. Of the most toxic heavy
      metals tested, only very high concentrations of Hg2+, CrO4 (2-) or Cu2+ killed
      surface-adherent Candida. Metal-chelator precipitates could be formed in biofilms
      following exposure to the heavy metals Cu2+ and Ni2+. This suggests that Candida
      biofilms may adsorb metal cations from their surroundings and that sequestration
      in the extracellular matrix may contribute to resistance. We concluded that
      biofilm formation may be a strategy for metal resistance and/or tolerance in
      yeasts.

PMID- 16466388
TI  - Runx3 controls growth and differentiation of gastric epithelial cells in mammals.
AB  - Runx3 is a transcription factor expressed by gastric epithelial cells. In the
      Runx3(-/-) mouse, gastric epithelia exhibited hyperplasia, and epithelial
      apoptosis was suppressed. By analyzing growth of the epithelial cells in primary
      culture, we found that Runx3(-/-) gastric epithelial cells are less sensitive to
      the growth-inhibitory and apoptosis-inducing activities of TGF-beta, suggesting
      that Runx3 is a major growth regulator of gastric epithelial cells by regulating
      their response to TGF-beta. We also found that Runx3 plays an important role in
      the control of gastric epithelial differentiation. When subcutaneously implanted
      into nude mice, Runx3(-/-) gastric epithelial cells formed tumors in which some
      cells differentiated into intestinal-type cells. Clonal analysis showed that
      gastric epithelial cells transdifferentiate into intestinal-type cells in the
      tumor. Considering that gastric epithelial differentiation is very stable, and
      that intestinal-type cells never differentiate in the mouse stomach, it is
      remarkable that gastric epithelial cells transdifferentiate into intestinal-type
      cells. We conclude that Runx3 is deeply involved in the control of both growth
      and differentiation of gastric epithelial cells. The role of Runx3 in the
      specification of gastric epithelial cells is discussed.

PMID- 16466389
TI  - Functional regeneration of the olfactory bulb requires reconnection to the
      olfactory nerve in Xenopus larvae.
AB  - Larvae of the South African clawed frog (Xenopus laevis) can regenerate the
      telencephalon, which consists of the olfactory bulb and the cerebrum, after it
      has been partially removed. Some authors have argued that the telencephalon, once
      removed, must be reconnected to the olfactory nerve in order to regenerate.
      However, considerable regeneration has been observed before reconnection.
      Therefore, we have conducted several experiments to learn whether or not
      reconnection is a prerequisite for regeneration. We found that the olfactory bulb
      did not regenerate without reconnection, while the cerebrum regenerated by
      itself. On the other hand, when the brain was reconnected by the olfactory nerve,
      both the cerebrum and the olfactory bulb regenerated. Morphological and
      histological investigation showed that the regenerated telencephalon was
      identical to the intact one in morphology, types and distributions of cells, and
      connections between neurons. Froglets with a regenerated telencephalon also
      recovered olfaction, the primary function of the frog telencephalon. These
      results suggest that the Xenopus larva requires reconnection of the regenerating
      brain to the olfactory nerve in order to regenerate the olfactory bulb, and thus
      the regenerated brain functions, in order to process olfactory information.

PMID- 16466390
TI  - Cell cycle control by daf-21/Hsp90 at the first meiotic prophase/metaphase
      boundary during oogenesis in Caenorhabditis elegans.
AB  - DAF-21, a Caenorhabditis elegans homologue of Hsp90, is expressed primarily in
      germline cells. Although mutations in the daf-21 gene affect animal fertility,
      its cellular roles have remained elusive. To phenocopy daf-21 mutations, we
      impaired the daf-21 function by RNA interference (RNAi), and found that oocytes
      skipped the diakinesis arrest and displayed a defective diakinesis arrest, which
      led to the production of endomitotic oocytes with polyploid chromosomes (Emo
      phenotype). The same Emo phenotype was also observed with RNAi against wee-1.3.
      To identify a cause for Emo, we examined the CDK-1 (Cdc2) phosphorylation status
      in Emo animals, since CDK-1 is a key regulator of the prophase/metaphase
      transition and is kept inactivated by WEE-1.3 kinase during prophase. We
      immunostained both daf-21(RNAi) and wee-1.3(RNAi) animals with anti
      phosphorylated-CDK-1 antibody and observed no detectable phosphates on CDK-1 in
      either of the animals. We also examined WEE-1.3 expression in daf-21(RNAi) and
      found a significant reduction of WEE-1.3. These results indicate that CDK-1 was
      not phosphorylated in either daf-21(RNAi) or wee-1.3(RNAi) animals, and suggest
      that daf-21 was necessary for producing functional WEE-1.3. Thus, all together,
      we propose that DAF-21 indirectly regulates the meiotic prophase/metaphase
      transition during oocyte development by ensuring the normal function of WEE-1.3.

PMID- 16466391
TI  - Sperm-egg interaction is mediated by a sperm-associated body in quail.
AB  - The present study describes the holes in the inner vitelline membrane of fertile
      eggs of the quail Coturnix japonica, which remain after the spermatozoa pass
      through. It was shown that the light-microscopically observable 'holes'
      correspond mostly to electron-microscopically defined 'disks', and, to a lesser
      extent (about 5%), real holes. Immunofluorescent staining of the vitelline
      membranes with an antiquail ZPC antiserum was used to discriminate the holes from
      the disks light-microscopically. Over 96% of holes were accompanied by calcium
      coated sperm-associated bodies, indicating a close relationship between the two.
      There was no preferential localization of the disks, holes or sperm-associated
      bodies in the vitelline membrane around the egg. The sperm-associated bodies
      bound with the spermatozoa at the posterior end of sperm flagella. Incubation of
      the inner vitelline membranes, isolated from the largest follicles, with
      spermatozoa resulted in production only of the disks, whereas the holes (about
      9%) were produced when the sperm-associated bodies were added to the system. It
      was suggested that the sperm-associated bodies assist fertile spermatozoa in
      binding to the inner vitelline membrane, making holes in the membrane and passing
      through them in fertile eggs.

PMID- 16466392
TI  - Investigation of the fate of Sry-expressing cells using an in vivo Cre/loxP
      system.
AB  - Sry (sex-determining region on Y chromosome) is expressed in the
      undifferentiated, bipotential genital ridges of mammalian XY fetuses. The
      expression of Sry initiates testis development, but the lineage of Sry-expressing
      cells is unclear. In this study, double-transgenic mice were analyzed using the
      Cre/loxP system. Cre under the control of the Sry promoter was expressed in the
      fetal gonads of transgenic mice similarly to endogenous Sry. The Sry/Cre
      transgenic mice were crossed with CAG(cytomegalovirus immediate-early enhancer,
      chicken beta-actin promoter and fusion intron of chicken beta-actin and rabbit
      beta-globin)/loxP/CAT/loxP/LacZ-transgenic mice, in which the transgene expressed
      beta-galactosidase after a Cre-mediated recombination event. Sertoli cells, germ
      cells of testes and granulosa cells of ovaries of double-transgenic mice stained
      positive with X-gal. Cre expression was detected in germ cells and
      peritubular/Sertoli cells in adult testes. It is not clear whether beta
      galactosidase expression in the Sertoli cells of the testes occurred as a result
      of Cre expression in the adult or in the fetal gonads. These analyses indicate
      that cells expressing Sry-inducing factors in female fetal gonads become
      granulosa cells.

PMID- 16466393
TI  - Isolation of germline cells from Drosophila embryos by flow cytometry.
AB  - Primordial germ cells (PGC) are the earliest identifiable germ cells in the
      embryo. To understand the molecular basis of germline development, isolation of
      pure PGC is required. We report here the use of fluorescence-activated cell
      sorting (FACS) to isolate pure populations of Drosophila pole cells, which are
      the presumptive primordial germ cells in flies. In order to fluorescently mark
      pole cells, we used an EGFP-vasa transgenic line that expresses green fluorescent
      protein (GFP) specifically and continuously in the germ line throughout the life
      cycle. The purity of FACS-sorted pole cells from embryos was confirmed by
      microscopic inspection and quantitative polymerase chain reaction. Moreover, by
      optimizing the sample preparation and the sorting protocol, embryonic gonads
      could also be isolated. This technique opens the way for genome-wide
      transcriptome analysis of germline cells. In a pilot experiment, we generated a
      cDNA library from purified embryonic gonad and identified a novel germline
      specific gene, RpL22-like.

PMID- 16466394
TI  - Sex reversal in medaka treated in vitro with 17alpha-methyldihydrotestosterone
      during oocyte maturation.
AB  - Using the S-rR strain of the medaka Oryzias latipes, we examined the effect of a
      non-aromatizable androgen on sex determination. Intrafollicular immature oocytes
      isolated before breakdown of the germinal vesicle were incubated in the presence
      of 17alpha-methyldihydrotestosterone (MDHT) for about 10 h during their
      maturational period. At the end of incubation, mature oocytes were rinsed and
      then artificially inseminated in regular saline. The fertilized eggs were then
      allowed to develop in tap water, and the fry were reared on a regular powdered
      diet until adulthood. Sex reversal of female to male was observed in a manner
      dependent on the dose of MDHT. In the solvent control group in which
      intrafollicular oocytes were matured in medium containing no exogenous androgen,
      no sex reversal was observed. The present finding, that the sex of medakas can be
      reversed by a single in vitro exposure of immature oocytes to androgen during the
      preovulatory period, suggests the existence in the oocyte of a sex determinant
      sensitive to sex steroids. This method for controlling the sex of eggs before
      fertilization may establish sex-determined eggs as potent material for
      investigating the mechanism of sex determination in the medaka.

PMID- 16466395
TI  - Cell type- and stage-specific changes in HOXA7 protein expression in human
      ovarian folliculogenesis: possible role of GDF-9.
AB  - Homeobox (HOX) genes are important transcriptional regulators in development and
      in adult tissues. A major obstacle to the understanding of their roles in humans
      has been the lack of well-defined anti-human HOX antibodies. We generated a
      thoroughly characterized polyclonal rabbit antibody against human HOXA7 and used
      it to study the distribution, role, and regulation of HOXA7 in human ovarian
      folliculogenesis and in granulosa cell tumors. Immunohistochemically, follicles
      were strongly HOXA7-positive compared with stroma. Oocytes expressed little
      HOXA7. Granulosa cells were predominantly negative in primordial follicles, had
      uniformly HOXA7-positive nuclei in primary follicles, and, as follicles matured,
      the subcellular localization of HOXA7 changed from nuclear to predominantly
      cytoplasmic. HOXA7 was mainly cytoplasmic in theca interna, but completely absent
      in theca externa. Granulosa cell tumors were mainly HOXA7 positive and, like in
      preovulatory follicles and theca interna, staining was predominantly cytoplasmic.
      The change in HOXA7 expression from negative primordial to positive primary
      follicles suggested a relationship with granulosa cell proliferation. To test
      this hypothesis, SV40 Tag-immortalized human granulosa cells (SVOG) were double
      stained with anti-HOXA7 antibody and with Ki-67 as proliferation marker. HOXA7
      expression was highest in mitotic cells. In addition, growth differentiation
      factor-9 (GDF-9), known to be secreted by oocytes in primary human follicles, up
      regulated HOXA7 protein, and stimulated proliferation of SVOG, while TGF-beta1
      inhibited HOXA7 expression and proliferation. This is the first report on the
      expression of any HOX gene in human ovarian follicles and granulosa cell tumors.
      It shows that HOXA7 undergoes cell type- and stage-specific changes during
      ovarian folliculogenesis, likely regulates granulosa cell proliferation, and in
      subcellular location differs between proliferating and secretory cells. The
      increase in HOXA7 protein in response to GDF-9 represents the first demonstration
      of a possible regulatory role of oocytes in ovarian follicular HOX gene
      expression.

PMID- 16466396
TI  - Energy metabolism of the inner cell mass and trophectoderm of the mouse
      blastocyst.
AB  - Mammalian pre-implantation development culminates in the formation of the
      blastocyst consisting of two distinct cell lineages, approximately a third of the
      cells comprise the pluripotent inner cell mass (ICM) and the remainder the
      differentiated trophectoderm (TE). However, the contribution made by these two
      cell types to the overall energy metabolism of the intact blastocyst has received
      relatively little attention. In this study, the metabolism of the intact mouse
      blastocyst and isolated ICMs were determined in terms of total ATP formation
      (calculated from oxygen consumption and lactate formation), mitochondrial
      distribution and amino acid turnover to provide an indication of protein
      synthesis. The TE consumed significantly more oxygen, produced more ATP and
      contained a greater number of mitochondria than the ICM. Amino acid turnover was
      significantly greater (p<0.001) in the TE compared with the ICM. Specifically,
      there was a significant difference in the utilization of aspartate (p=0.020),
      glutamate (p=0.024), methionine (p=0.037), and serine (p=0.041) between the cells
      of the ICM and TE. These data suggest that the TE produces approximately 80% of
      the ATP generated and is responsible for 90% of amino acid turnover compared with
      the ICM. The major fate of the energy produced by the TE is likely to be the
      Na(+), K(+)ATPase (sodium pump enzyme) located on the TE basolateral membrane. In
      conclusion, the pluripotent cells of the ICM display a relatively quiescent
      metabolism in comparison with that of the TE.

PMID- 16466398
TI  - Serum response factor, its cofactors, and epithelial-mesenchymal signaling in
      urinary bladder smooth muscle formation.
AB  - Little is known about the mechanism of bladder smooth muscle differentiation. We
      hypothesize that epithelial-mesenchymal signaling induces the expression of
      smooth muscle proteins in bladder mesenchyme resulting in smooth muscle
      differentiation. We confirmed that smooth muscle differentiation in the mouse
      urinary bladder occurs first at gestational day 14 (E14) based upon
      immunohistochemical localization of smooth muscle alpha-actin (SMAA). To
      investigate murine bladder smooth muscle differentiation and epithlelial
      mesenchymal signaling in the developing bladder, we analyzed gene expression
      profiles of intact embryonic murine bladders and separated epithelial and
      mesenchymal components at embryonic days E13, E14, E15, E16, and postnatal day 1
      (P1). Using cDNA microarray, we identified regulators of vascular smooth muscle
      differentiation in bladder mesenchyme, including serum response factor (SRF) and
      its cofactors, ELK1 and SRF accessory protein (SAP)1, as well as two SRF
      associated pathways, angiotension receptor II and transforming growth factor-
      beta2. Immunohistochemistry showed diffuse expression of SRF in the bladder at
      E12 with localization of expression to the peripheral mesenchyme at E13 and E14.
      Our results suggest that bladder smooth muscle differentiation may share a
      similar gene expression program as occurs during vascular smooth muscle
      differentiation. The unique structure of the urinary bladder makes it an ideal
      model for studies of smooth muscle differentiation and epithelial-mesenchymal
      signaling.

PMID- 16466397
TI  - A role for chromosomal protein HMGN1 in corneal maturation.
AB  - Corneal differentiation and maturation are associated with major changes in the
      expression levels of numerous genes, including those coding for the chromatin
      binding high-mobility group (HMG) proteins. Here we report that HMGN1, a
      nucleosome-binding protein that alters the structure and activity of chromatin,
      affects the development of the corneal epithelium in mice. The corneal epithelium
      of Hmgn1(-/-) mice is thin, has a reduced number of cells, is poorly stratified,
      is depleted of suprabasal wing cells, and its most superficial cell layer
      blisters. In mature Hmgn1(-/-)mice, the basal cells retain the ovoid shape of
      immature cells, and rest directly on the basal membrane which is disorganized.
      Gene expression was modified in Hmgn1(-/-) corneas: glutathione-S-transferase
      (GST)alpha 4 and GST omega 1, epithelial layer-specific markers, were selectively
      reduced while E-cadherin and alpha-, beta-, and gamma-catenin, components of
      adherens junctions, were increased. Immunofluorescence analysis reveals a
      complete co-localization of HMGN1 and p 63 in small clusters of basal corneal
      epithelial cells of wild-type mice, and an absence of p 63 expressing cells in
      the central region of the Hmgn1(-/-) cornea. We suggest that interaction of HMGN1
      with chromatin modulates the fidelity of gene expression and affects corneal
      development and maturation.

PMID- 16466399
TI  - Transforming growth factor-beta signaling helps specify tumor type in DMBA and
      hormone-induced mammary cancers.
AB  - To determine the role of transforming growth factor-beta (TGF-beta) signaling in
      mammary development and tumor formation, we previously generated transgenic mice
      that expressed a dominant-negative form of the TGF-beta type II receptor (DNIIR)
      under the control of DNA regulatory elements from the metallothionein promoter
      (MT-DNIIR-28). In this report, we tested the hypothesis that loss of TGF-beta
      signaling in the mammary gland alters the development of chemically or hormonally
      induced tumors in mice. Four groups of mice were used in the study: wild-type and
      MT-DNIIR-28 mice on zinc with pituitary isograft, and wild-type and MT-DNIIR-28
      mice on zinc with pituitary isograft treated with the carcinogen, 7,12
      dimethylbenz[a]anthracene (DMBA). Tumor-free survival over time, tumor growth
      rate, and tumor pathology were measured. Statistically significant differences in
      tumor free survival over time or tumor growth rate were not detected in wild-type
      versus transgenic mice treated with DMBA. In contrast, tumor-free survival was
      significantly altered in transgenic mice that were treated with the pituitary
      isograft alone with MT-DNIIR mice developing tumors more quickly. Alterations in
      the types of tumors that formed in wild-type versus MT-DNIIR DMBA-treated mice
      were detected. In wild-type mice, tumors with squamous differentiation or
      bicellular adenomyoepitheliomas were most common. Adenomyoepitheliomas were not
      detected in transgenic mice. Furthermore, there was reduced staining for alpha
      smooth muscle actin and keratin 14, markers for myoepithelial cells, in the
      glandular portion of tumors in transgenic mice. The pathology of tumors induced
      by pituitary isograft alone was also markedly different in wild-type and
      transgenic mice. All the tumors classified from wild-type mice demonstrated some
      form of squamous differentiation, whereas squamous differentiation was not
      detected in the pituitary-induced transgenic tumors. The results suggest that TGF
      beta acts as a tumor suppressor for hormone-induced cancers and that TGF-beta has
      a role in determining tumor pathology by regulating myoepithelial or squamous
      differentiation, maintenance, or transformation.

PMID- 16466401
TI  - Attitudes towards medication in patients with schizophrenia.

PMID- 16466400
TI  - Ribozyme-mediated perlecan knockdown impairs chondrogenic differentiation of
      C3H10T1/2 fibroblasts.
AB  - Perlecan (Pln) is an abundant heparan sulfate (HS) proteoglycan in the
      pericellular matrix of developing cartilage, and its absence dramatically
      disrupts endochondral bone formation. This study examined two previously
      unexamined aspects of the function of Pln in mesenchymal chondrogenesis in vitro.
      Using the well-established high-density micromass model of chondrogenic
      differentiation, we first examined the requirement for endogenous Pln synthesis
      and secretion through the use of Pln-targeted ribozymes in murine C3H10T1/2
      embryonic fibroblasts. Second, we examined the ability of the unique N-terminal,
      HS-bearing Pln domain I (PlnDI) to synergize with exogenous bone morphogenetic
      protein-2 (BMP-2) to support later stage chondrogenic maturation of cellular
      condensations. The results provide clear evidence that the function of Pln in
      late stage chondrogenesis requires Pln biosynthesis and secretion, because 60%
      70% reductions in Pln greatly diminish chondrogenic marker expression in
      micromass culture. Additionally, these data support the idea that while early
      chondrocyte differentiation can be supported by exogenous HS-decorated PlnDI,
      efficient late stage PlnDI-supported chondrogenesis requires both BMP-2 and Pln
      biosynthesis.

PMID- 16466402
TI  - Public beliefs about and attitudes towards people with mental illness: a review
      of population studies.
AB  - OBJECTIVE: To provide a review of population-based attitude research in
      psychiatry during the past 15 years. METHOD: An electronic search using PubMed,
      Medline, and Academic Search Premier plus a hand search of the literature was
      carried out for studies on public beliefs about mental illness and attitudes
      towards the mentally ill published between 1990 and 2004. RESULTS: Thirty-three
      national studies and 29 local and regional studies were identified, mostly from
      Europe. Although the majority are of descriptive nature, more recent publications
      include studies testing theory-based models of the stigmatization of mentally ill
      people, analyses of time trends and cross-cultural comparisons, and evaluations
      of antistigma interventions. CONCLUSION: Attitude research in psychiatry made
      considerable progress over the past 15 years. However, there is still much to be
      done to provide an empirical basis for evidence-based interventions to reduce
      misconceptions about mental illness and improve attitudes towards persons with
      mental illness.

PMID- 16466403
TI  - Personality traits as correlates of suicidal ideation, suicide attempts, and
      suicide completions: a systematic review.
AB  - OBJECTIVE: Involvement of personality traits in susceptibility to suicidality has
      been the subject of research since the 1950s. Because of the diversity of
      conceptual and methodological approaches, the extent of their independent
      contribution has been difficult to establish. Here, we review conceptual
      background and empirical evidence investigating roles of traits in suicidal
      behaviors. METHOD: We selected original studies published in English in MEDLINE
      and PsycINFO databases, focusing on suicidal ideation, suicide attempts, or
      suicide completions, and using standardized personality measures. RESULTS: Most
      studies focused on investigating risk for suicide attempts. Hopelessness,
      neuroticism, and extroversion hold the most promise in relation to risk screening
      across all three suicidal behaviors. More research is needed regarding
      aggression, impulsivity, anger, irritability, hostility, and anxiety. CONCLUSION:
      Selected personality traits may be useful markers of suicide risk. Future
      research needs to establish their contributions in relation to environmental and
      genetic variation in different gender, age, and ethnocultural groups.

PMID- 16466404
TI  - Attitude towards antipsychotics among out-patients with schizophrenia in Nigeria.
AB  - OBJECTIVE: The study aim to assess the attitude of patients with schizophrenia
      attending out-patient clinics in Nigeria towards antipsychotic medication and
      examine the factors associated with such attitude. METHOD: Out-patients with
      schizophrenia (n = 312) completed the 10-item Drug Attitude Inventory. They were
      also evaluated for sociodemographic details, illness-related and drug-related
      variables. RESULTS: Overall, the patients had a good attitude towards
      antipsychotic medication. The factors significantly associated with poor attitude
      towards medication include presence of symptoms, presence of side-effects like
      dyskinesia and sedation, lack of insight into the illness, and being employed.
      CONCLUSION: Special attention should be paid to patients with these factors while
      designing programmes to improve overall compliance in patients with
      schizophrenia.

PMID- 16466405
TI  - The prescription of psychotropic drugs in psychiatric residential facilities: a
      national survey in Italy.
AB  - OBJECTIVE: This paper reports the prescriptions of psychotropic drugs made to
      2962 patients living in 265 residential facilities (RFs) in Italy. METHOD:
      Structured interviews were administered to RF managers and staff to obtain data
      on patients' sociodemographic and clinical characteristics; information about
      current drug prescriptions were obtained from clinical records. RESULTS:
      Polypharmacy was common: on average, each treated patient was taking 2.7 drugs
      (+/-1.1). The association of one atypical antipsychotic with one benzodiazepine
      represented the most common prescription profile. The variable most consistently
      associated with a higher likelihood of receiving polypharmacy was a history of
      admission to an acute general hospital psychiatric ward in the previous 12
      months. Many prescriptions were loosely related to specific diagnoses.
      CONCLUSION: Psychotropic drug prescription patterns for severe patients living in
      RFs are characterized by substantial rates of polypharmacy. Specific guidelines
      may be helpful for long-stay patients living in RFs, who exhibit complex care
      needs.

PMID- 16466406
TI  - Nurses' short-term prediction of violence in acute psychiatric intensive care.
AB  - OBJECTIVE: To evaluate the short-term predictive capacity of the Broset Violence
      Checklist (BVC) when used by nurses in a psychiatric intensive care unit. METHOD:
      Seventy-three patients were assessed according to the BVC three times daily.
      Violent incidents were recorded with the Staff Observation Aggression Scale,
      revised version. An extended Cox proportional hazards model with multiple events
      and time-dependent covariates was estimated to evaluate how the highest BVC sum
      of the last 24 h and its separate items affect the risk for severe violence
      within the next 24 h. RESULTS: With a BVC sum of one or more, hazard for severe
      violence was six times higher than if the sum was zero. Four of the six separate
      items significantly increased the risk for severe violence with hazard ratios
      between 3.0 and 6.3. CONCLUSION: Risk for in-patient violence in a short-term
      perspective can to a high degree be predicted by nurses using the BVC.

PMID- 16466407
TI  - Is paternal postpartum depression associated with maternal postpartum depression?
      Population-based study in Brazil.
AB  - OBJECTIVE: To describe the prevalence of paternal postpartum depression (PPD) as
      well as its association with maternal PPD. METHOD: A population-based random
      sample of 386 couples was assessed from the sixth to the 12th week postpartum for
      demographic characteristics, alcohol misuse (AUDIT) and depressive symptoms [Beck
      Depression Inventory (BDI)]. Logistic regression was employed to control for
      potential confounders. RESULTS: In the BDI, 26.3% of mothers and 11.9% of fathers
      scored above the selected threshold of 10. Mild maternal depression [odds ratio
      (OR) 3.31, 95% CI 1.52-7.20] and moderate to severe maternal depression (OR 8.44,
      95% CI 3.53-20.21) were associated with paternal PPD. CONCLUSION: Paternal PPD is
      a clinically meaningful phenomenon. Fathers should be evaluated for mood
      disorders in the postpartum, especially when their partner is depressed.

PMID- 16466408
TI  - Dimensional characteristics of DSM-IV personality disorders in a large
      epidemiological sample.
AB  - OBJECTIVE: To assess the five-factor model (FFM) characteristics of young adults
      with Diagnostic Statistical Manual-IV (DSM-IV) personality disorders in a large
      community study. METHOD: As part of the eighth wave of a cohort study, 1469 young
      adults (mean age: 24 years) completed the NEO-five factor inventory, 1145 of whom
      also had an informant-based personality disorder assessment. RESULTS: The
      prevalence of personality disorder was 18.6% (95% CI: 16.5-20.7). There were
      consistent positive associations with neuroticism and negative associations with
      agreeableness across all three clusters of personality disorder. CONCLUSION: In
      young adults, high neuroticism and low agreeableness are consistent dimensional
      characteristics of all personality disorder clusters.

PMID- 16466410
TI  - Suicide with hostile intent in the Bible.

PMID- 16466412
TI  - Child abuse and psychosis.

PMID- 16466414
TI  - Suggestion reduces the stroop effect.
AB  - We examined the effects of suggestion on Stroop interference in highly
      suggestible individuals. Participants completed the Stroop task with and without
      a suggestion to perceive Stroop words as meaningless symbols. Half the
      participants were given this suggestion in hypnosis, and half were given the
      suggestion without the induction of hypnosis. Suggestion produced a significant
      reduction in Stroop inhibition, accounting for about 45% of the variance in
      Stroop responding, regardless of whether hypnosis had been induced. These
      findings indicate that suggestion can at least partially overcome the
      automaticity associated with the Stroop effect.

PMID- 16466415
TI  - New data analysis of the stroop matching task calls for a reevaluation of theory.
AB  - In Stroop matching tasks, participants indicate whether the color of an object
      matches the meaning of a color word printed in color. Previously in this journal,
      Luo (1999) concluded that interference between two incongruent representations of
      the same attribute (ink color) occurs prior to the response stage. However, this
      conclusion was based on questionable data analysis. We suggest analyzing the data
      by separating "same" and "different" responses and then analyzing three
      congruency conditions within the "different" responses: (a) congruence between
      word color and word meaning, (b) congruence between word color and object color,
      and (c) incongruence between word color, word meaning, and object color. In an
      experiment similar to Luo's, such an analysis revealed that responding was
      slowest in the first condition. This pattern of results does not fit with
      previous conclusions regarding this task, but rather indicates that task conflict
      and response competition contribute to interference. This analysis has
      implications for matching tasks other than the Stroop matching task.

PMID- 16466416
TI  - Cue duration and parvocellular guidance of visual attention.

PMID- 16466417
TI  - Going for the gold. Models of agency in Japanese and American contexts.
AB  - Two studies examined how Olympic performance is explained in American and
      Japanese contexts. Study 1, an analysis of media coverage of the 2000 and 2002
      Olympics, shows that in both Japanese and American contexts, performance is
      construed mainly in terms of the actions of persons. However, Japanese and
      American accounts differ in their explanations of the nature and source of
      intentional agency, that is, in their models of agency. In Japanese contexts,
      agency is construed as conjoint and simultaneously implicates athletes' personal
      attributes (both positive and negative), background, and social and emotional
      experience. In American contexts, agency is construed as disjoint, separate from
      athletes' background or social and emotional experience; performance is explained
      primarily through positive personal characteristics and features of the
      competition. Study 2, in which participants chose information to be included in
      an athlete's description, confirms these findings. Differences in the
      construction of agency are reflected in and fostered by common cultural products
      (e.g., television accounts).

PMID- 16466418
TI  - Culture and the physical environment. Holistic versus analytic perceptual
      affordances.
AB  - Westerners' perceptions tend to focus on salient foreground objects, whereas
      Asians are more inclined to focus on contexts. We hypothesized that such
      culturally specific patterns of attention may be afforded by the perceptual
      environment of each culture. In order to test this hypothesis, we randomly
      sampled pictures of scenes from small, medium, and large cities in Japan and the
      United States. Using both subjective and objective measures, Study 1 demonstrated
      that Japanese scenes were more ambiguous and contained more elements than
      American scenes. Japanese scenes thus may encourage perception of the context
      more than American scenes. In Study 2, pictures of locations in cities were
      presented as primes, and participants' subsequent patterns of attention were
      measured. Both Japanese and American participants primed with Japanese scenes
      attended more to contextual information than did those primed with American
      scenes. These results provide evidence that culturally characteristic
      environments may afford distinctive patterns of perception.

PMID- 16466419
TI  - Expanding the topography of social anxiety. An experience-sampling assessment of
      positive emotions, positive events, and emotion suppression.
AB  - The relation between social anxiety and hedonic activity remains poorly
      understood. From a self-regulatory perspective, we hypothesized that socially
      anxious individuals experience diminished positive experiences and events on days
      when they are unable to manage socially anxious feelings adequately. In this 21
      day experience-sampling study, we constructed daily measures of social anxiety
      and emotion regulation. Greater dispositional social anxiety was associated with
      less positive affect and fewer positive events in everyday life. Among
      individuals defined as socially anxious from their scores on a global self-report
      measure of social anxiety, the number of positive events was lowest on days when
      they both were more socially anxious and tended to suppress emotions and highest
      on days when they were less socially anxious and more accepting of emotional
      experiences. Irrespective of dispositional social anxiety, participants reported
      the most intense positive emotions on the days when they were both least socially
      anxious and most accepting of emotional experiences. Possible clinical
      implications are discussed.

PMID- 16466420
TI  - Essentializing differences between women and men.
AB  - People represent many social categories, including gender categories, in
      essentialist terms: They see category members as sharing deep, nonobvious
      properties that make them the kinds of things they are. The present research
      explored the consequences of this mode of representation for social inferences.
      In two sets of studies, participants learned (a) that they were similar to a
      member of the other gender on a novel attribute, (b) that they were different
      from a member of the other gender on a novel attribute, or (c) just their own
      standing on a novel attribute. Results showed that participants made stronger
      inductive inferences about the attribute in question when they learned that it
      distinguished them from a member of the other gender than in the other
      conditions. We consider the implications of these results for the representation
      of social categories and for everyday social inference processes.

PMID- 16466421
TI  - Turning the other cheek. Agreeableness and the regulation of aggression-related
      primes.
AB  - Aggression-related cues (e.g., violent media) can prime both hostile thoughts and
      the tendency to commit aggression. However, not everyone engages in an aggressive
      act after being exposed to an aggression-related cue. Some thought pattern,
      perhaps an automatic one, may prevent the cue-aggression sequence in some
      individuals. These considerations motivated the present research, which examined
      the potential for agreeableness to moderate the effect of aggression-related cues
      on behavior and cognition. In Study 1, we found that priming with aggression
      related cues increased aggressive behavior, but only among individuals low in
      agreeableness. Study 2 showed that aggression-related cues activated prosocial
      thoughts among individuals high in agreeable affect (a component of
      agreeableness). These results reveal that agreeable individuals are able to short
      circuit the cue-aggression sequence, likely by recruiting prosocial thoughts in
      response to aggression-related primes.

PMID- 16466422
TI  - Doing better but feeling worse. Looking for the "best" job undermines
      satisfaction.
AB  - Expanding upon Simon's (1955) seminal theory, this investigation compared the
      choice-making strategies of maximizers and satisficers, finding that maximizing
      tendencies, although positively correlated with objectively better decision
      outcomes, are also associated with more negative subjective evaluations of these
      decision outcomes. Specifically, in the fall of their final year in school,
      students were administered a scale that measured maximizing tendencies and were
      then followed over the course of the year as they searched for jobs. Students
      with high maximizing tendencies secured jobs with 20% higher starting salaries
      than did students with low maximizing tendencies. However, maximizers were less
      satisfied than satisficers with the jobs they obtained, and experienced more
      negative affect throughout the job-search process. These effects were mediated by
      maximizers' greater reliance on external sources of information and their
      fixation on realized and unrealized options during the search and selection
      process.

PMID- 16466423
TI  - Stability in cognition across early childhood. A developmental cascade.
AB  - Children confront the formidable task of assimilating information in the
      environment and accommodating their cognitive structures to that information.
      Developmental science is concerned equally with two distinctive features of these
      processes: children's group mean level of performance through time and the
      standing of individual children through time. Prevailing opinion since the
      inception of the mental-measurement movement has been that individual development
      is unstable-that individual children change unpredictably in their abilities. We
      report results of a large-scale controlled, multivariate, prospective,
      microgenetic, 4-year longitudinal study that reveals a statistically significant
      cascade of species-typical cognitive abilities from infancy to childhood. Infancy
      is a recognizable starting point of life; we find that to a small but significant
      degree, infancy also represents a setting point in the life of the individual.

PMID- 16466424
TI  - Nature and nurture in own-race face processing.
AB  - A standard visual preference task was used to examine 3-month-olds' looking times
      at own-race versus other-race faces as a function of environmental exposure to
      faces from the two categories. Participants were Caucasian infants living in a
      Caucasian environment, African infants living in an African environment, and
      African infants living in a predominantly Caucasian environment. The results
      indicate that preference for own-race faces is present as early as 3 months of
      age, but that this preference results from exposure to the prototypical facial
      environment.

PMID- 16466425
TI  - The impact of cognitive deficits on conflict monitoring. Predictable
      dissociations between the error-related negativity and N2.
AB  - Monitoring of ongoing processing plays a critical role in regulating cognitive
      function. Two event-related potential components, the error-related negativity
      (ERN) and N2, have been proposed to reflect this monitoring function.
      Specifically, it has been suggested that both components reflect the role of
      anterior cingulate cortex (ACC) in monitoring for the occurrence of response
      conflict. This view appears to be challenged by findings that alcohol consumption
      and lesions in ACC have dissociable effects on the ERN and N2. Using a
      computational model, the present research demonstrates that the conflict
      monitoring theory can account for these dissociations in terms of the dissociable
      effects of alcohol and ACC lesions on processing of relevant stimulus information
      (which determines ERN amplitude) and processing of irrelevant, distracting
      information (which determines N2 amplitude). The simulation results suggest new
      interpretations of the cognitive deficits caused by alcohol consumption (impaired
      stimulus processing) and ACC lesions (impaired attentional control).

PMID- 16466426
TI  - Not all executive functions are related to intelligence.
AB  - Accumulating evidence suggests that executive functions (EFs) are related to
      intelligence, despite neuropsychological results initially considered evidence of
      no such relation. However, findings that EFs are not unitary raise the issue of
      how intelligence relates to different EFs. This study examined the relations of
      fluid and crystallized intelligence and Wechsler Adult Intelligence Scale IQ to
      three separable EFs--inhibiting prepotent responses (inhibiting), shifting mental
      sets (shifting), and updating working memory (updating)--in young adults.
      Updating was highly correlated with the intelligence measures, but inhibiting and
      shifting were not. Furthermore, in structural equation models controlling for the
      inter-EF correlations, updating remained strongly related to intelligence, but
      the relations of inhibiting and shifting to intelligence were small and not
      significant. The results indicate that intelligence measures differentially
      relate to these three EFs, suggesting that current intelligence measures do not
      equally assess a wide range of executive control abilities likely required for
      many "intelligent" behaviors.

PMID- 16466427
TI  - The influence of maternal cigarette smoking, snuff use and passive smoking on
      pregnancy outcomes: the Birth To Ten Study.
AB  - This article describes the patterns and effects of maternal snuff use, cigarette
      smoking and exposure to environmental tobacco smoke during pregnancy on
      birthweight and gestational age, in women living in Johannesburg and Soweto in
      1990. A cohort of 1593 women with singleton live births provided information
      about their own and household members' usage of tobacco products during
      pregnancy. The women completed a questionnaire while attending antenatal
      services. Data on gestational age and birthweight were obtained from birth
      records. Women who smoked cigarettes or used snuff during pregnancy accounted for
      6.1% and 7.5% of the study population respectively. The mean birthweight of non
      tobacco users was 3148 g [95% CI 3123, 3173] and that of the smokers 2982 g [95%
      CI 2875, 3090], resulting in a significantly lower mean birthweight of 165 g for
      babies of smoking mothers (P = 0.005). In contrast, women using snuff gave birth
      to infants with a mean birthweight of 3118 g [95% CI 3043, 3192], which is a non
      significant (P = 0.52) decrease (29.4 g) in their infants' birthweights compared
      with those not using tobacco. A linear regression analysis identified short
      gestational age, female infant, a mother without hypertension during pregnancy,
      coloured (mixed racial ancestry), and Asian infants compared with black infants,
      lower parity, less than 12 years of education and smoking cigarettes as
      significant predictors of low birthweight, while the use of snuff during
      pregnancy was not associated with low birthweight. The snuff users, however, had
      a significant shorter gestational age than the other two groups of women. The
      birthweight reduction adjusted for possible confounders was 137 g [95% CI 26.6,
      247.3 (P = 0.015)] for cigarette smokers and 17.1 g [95% CI -69.5, -102.7, P =
      0.69] for snuff users respectively, compared with the birthweight of non-tobacco
      users. Among women who did not smoke cigarettes or use snuff, exposure to
      environmental tobacco smoke did not result in significant effects on the
      birthweight of their infants. In conclusion, infants of cigarette smokers had
      significantly lower birthweights than those of non-tobacco users or snuff users
      who are exposed to nicotine during pregnancy. Passive smoking did not affect
      birthweight significantly in this population.

PMID- 16466428
TI  - Maternal caffeine consumption and fetal death: a case-control study in Uruguay.
AB  - The objective of this study was to examine the association between caffeine
      intake during pregnancy and fetal mortality in Montevideo, the capital city of
      Uruguay, taking into account several potential confounding factors. A population
      based case-control study was conducted between 1 August 2002 and 31 December
      2003. A total of 382 cases and 792 controls were recruited. Cases consisted of
      women hospitalised with a medically confirmed diagnosis of spontaneous antepartum
      fetal death, in all maternity hospitals during the study period. Antepartum fetal
      death was defined as a fetal death in which the attending doctor certified that
      the death occurred prior to the onset of labour. Fetal deaths were included if
      they were of at least 20 weeks' gestational age or weighed >350 g. Controls were
      women who had a live, vigorous and term adequate-for-gestational-age newborn.
      Multiple gestations and fetuses/newborns with evident congenital malformations
      were excluded. Only a small proportion of the mothers (8.1% of the cases and 9.5%
      of the controls) did not consume caffeine during pregnancy. Among consumers, mate
      drinking was the most frequent source of caffeine in both cases and controls.
      After controlling for mother's and her partner's education, history of abortions
      and/or fetal deaths, vomiting/nausea during the first trimester of gestation and
      attendance for prenatal care, the category of mean caffeine intake of > or = 300
      mg/day showed a significantly increased risk of fetal death (OR 2.33 [1.23;
      4.41]) compared with no caffeine consumption during pregnancy. The study also
      found that less-educated women, mothers who did not attend for prenatal care and
      women with a history of abortions and fetal death were at an increased risk of
      fetal death. As mate drinking is highly consumed among pregnant women in Uruguay,
      the association found with fetal death makes it a preventable risk factor.

PMID- 16466429
TI  - Parental marijuana use and risk of childhood acute myeloid leukaemia: a report
      from the Children's Cancer Group (United States and Canada).
AB  - The aetiology of childhood acute myeloid leukaemia (AML) is largely unknown.
      Maternal marijuana use just before, or during pregnancy has been previously
      associated with childhood AML. This case-control investigation formally tested
      the hypothesis that parental marijuana use increases the risk of childhood AML in
      offspring. Incident cases of AML <18 years of age, diagnosed between 1989 and
      1993, and registered with the Children's Cancer Group (a paediatric clinical co
      operative group), were eligible for inclusion. Control children were selected via
      random digit dialling and individually matched 1:1 to cases on age, race and
      residential location, except for rare morphological subtypes that were matched
      1:2. Parental telephone interviews were conducted to determine exposure and
      covariate information. Conditional logistic regression was used to estimate
      matched odds ratios (OR) and 95% confidence intervals [CI] adjusted for household
      income, parental education and parental age. The analysis included 517 cases and
      610 matched controls. A series of sensitivity analyses examined the potential for
      recall bias. Ever lifetime use of marijuana by mothers was not associated with
      childhood AML [OR = 0.89; 95% CI = 0.66, 1.19]. Maternal marijuana use any time
      during the 3 months before, or during pregnancy was inversely associated with
      childhood AML [OR = 0.43; 95% CI = 0.23, 0.80]. Paternal use during the same time
      period was not associated with risk. Assuming a large degree of differential
      exposure misclassification was present, the corrected ORs ranged between 0.82 and
      1.40. The previously reported positive association between maternal marijuana use
      before or during pregnancy and childhood AML was not confirmed. The decreased ORs
      observed in this study may be due to recall bias assuming plausibly low values of
      sensitivity.

PMID- 16466430
TI  - Risks of repeated miscarriage.
AB  - There is a lack of well-designed epidemiological studies of possible risk factors
      for repeated miscarriage. In this Swedish population-based case-control study, we
      investigated the association between sociodemographic and anthropometric factors,
      obstetric history and life-style factors, with respect to the risks of first
      trimester repeated miscarriage. Information on maternal characteristics was
      collected through in-person interviews. Plasma blood samples were analysed for
      cotinine and folate concentrations. Adjusted odds ratios (OR) with 95% confidence
      interval [CI] were used to estimate the relative risk of repeated miscarriage.
      The risks of repeated miscarriage were increased for women aged > or = 35 years
      (adjusted OR 2.9 [95% CI 1.4, 5.8]), as well as for women aged < or = 24 years
      (OR 2.8 [95% CI 1.1, 6.8]). Women with a history of at least one preceding
      miscarriage prior to the two index pregnancies, women reporting prolonged time to
      conceive, and women with a history of myoma, faced a more than fourfold increased
      risk of repeated miscarriage. Smokers were at an increased risk of repeated
      miscarriage (OR 2.1 [95% CI 1.1, 4.1]). Among non-smoking women with high
      caffeine intake, there was an increased risk of repeated miscarriage, whereas
      there was no such association among smokers. Low plasma folate levels were not
      associated with increased risks.

PMID- 16466431
TI  - Investigating variations in infant mortality in England and Wales by mother's
      country of birth, 1983-2001.
AB  - The aim of this study was to investigate variations in infant mortality from 1983
      to 2001 by birthweight, registration status, father's social class, age of mother
      at birth and cause of death, among babies of mothers born in countries that
      represent the largest ethnic minority groups in England and Wales. A total of
      70,208 infant death registration records linked to their corresponding birth
      registration records were used. The study focused on infant deaths of babies of
      mothers born in the UK, Republic of Ireland, Caribbean, West Africa, East Africa,
      India, Pakistan and Bangladesh. From 1983 to 2001 infant mortality rates
      decreased overall, and this was also apparent in the rates by mother's country of
      birth. Overall, babies of mothers born in Pakistan consistently had the highest
      infant mortality rates. Low-birthweight babies of mothers born in West Africa had
      the highest infant, neonatal and postneonatal death rates. Differences were also
      seen by registration status, mother's age and between manual and non-manual
      occupations for all countries from 1983 to 2001. For babies of mothers born in
      the UK, Caribbean and West Africa, immaturity-related conditions were the most
      common cause of infant deaths. The leading cause of infant death among babies of
      mothers born in Pakistan and Bangladesh was congenital anomalies.

PMID- 16466432
TI  - Ethnic differences in total and cause-specific infant mortality in The
      Netherlands.
AB  - We examined ethnic differences in infant mortality and the contribution of
      several explanatory variables. Data of Statistics Netherlands from 1995 to 2000
      were studied (1,178,949 live borns). Proportional hazard analysis was used to
      show ethnic differences in total and cause-specific infant mortality. Obstetric,
      demographic and -geographical variables, and socio-economic status were
      considered as possible determinants. The four major ethnic minority groups showed
      an elevated risk of infant mortality, ranging from 1.28 in Turkish infants to
      1.50 in Antillean/Aruban infants. In the early neonatal period, risks were
      elevated for Surinamese (hazard ratio [HR] 1.48, 95% confidence intervals [CI]
      1.23, 1.78) and Antilleans/Arubans (HR 1.43, 95% CI 1.06, 1.92). In the post
      neonatal period, risks were only elevated for Turkish (HR 2.20, 95% CI 1.80,
      2.69) and Moroccan infants (HR 2.06, 95% CI 1.67, 2.55). Surinamese and
      Antillean/Aruban infants had an elevated risk of dying from perinatal causes (HR
      1.62, 95% CI 1.33, 1.98 and 1.69, 95% CI 1.24, 2.29 respectively), Turkish and
      Moroccan infants had an elevated risk of dying from congenital anomalies (HR
      1.42, 95% CI 1.16, 1.73 and 1.46, 95% CI 1.20, 1.79 respectively). Inequalities
      as a result of socio-economic position and demographic factors, such as marital
      status and maternal age, partially explain the ethnic differences in infant
      mortality. We conclude that ethnic minority groups in The Netherlands have a
      higher infant mortality than the native population, which in part seems
      preventable by reducing inequalities in socio-economic status. Marital status and
      age of the mother are important other risk factors of infant mortality.

PMID- 16466433
TI  - Early life predictors of childhood intelligence: findings from the Mater
      University study of pregnancy and its outcomes.
AB  - Growing evidence linking childhood intelligence with adult health outcomes
      suggests a need to identify predictors of this psychological characteristic. In
      this study, we have examined the early life determinants of childhood
      intelligence in a population-based birth cohort of individuals born in Brisbane,
      Australia between 1981 and 1984. In univariable analyses, family income in the
      year of birth, maternal and paternal education, maternal age at birth, maternal
      ethnicity, maternal smoking during pregnancy, duration of labour, birthweight,
      breast feeding and childhood height, and body mass index were all associated with
      intelligence at age 14. In multivariable analyses, the strongest and most robust
      predictors of intelligence were family income, parental education and breast
      feeding, with these three variables explaining 7.5% of the variation in
      intelligence at age 14. Addition of other variables added little further
      explanatory power. Our results demonstrate the importance of indicators of socio
      economic position as predictors of intelligence, and illustrate the need to
      consider the role of such factors in generating the association of childhood
      intelligence with adult disease risk.

PMID- 16466434
TI  - Systematic review of adverse outcomes of external cephalic version and persisting
      breech presentation at term.
AB  - The aim of this study was to determine the frequency of adverse maternal and
      fetal outcomes of both external cephalic version (ECV) and persisting breech
      presentation at term. We conducted a systematic review of the literature using
      Medline, Embase and All Evidence Based Medicine (EBM) Reviews databases. Data
      were extracted from studies that compared women who had an ECV from 36 weeks'
      gestation with a similar control group of women enrolled at the same gestational
      age, eligible for, but who did not have an ECV. Eleven studies with a total of
      2503 women were included. Adverse outcomes related to ECV were rarely reported
      and in most studies there was no evidence that relevant outcomes were ascertained
      among similar women who did not have an ECV. There was no increased risk of
      antepartum fetal death associated with ECV, but numbers were small. There were no
      reported cases of uterine rupture, placental abruption, prelabour rupture of
      membranes or cord prolapse, but these outcomes were not examined among controls.
      Onset of labour within 24 h and nuchal cord was non-significantly higher among
      women who had an ECV compared with those with a persisting breech. Despite
      limited reporting and small numbers, the results of our review suggest that
      adverse maternal and fetal outcomes of both ECV and persisting breech
      presentation are rare. Only with improved reporting and collection of safety data
      on ECV and persisting breech presentation can we provide high-quality information
      to assist informed decision making by pregnant women with a breech presentation
      at term.

PMID- 16466435
TI  - The Exeter Family Study of Childhood Health (EFSOCH): study protocol and
      methodology.
AB  - The Exeter Family Study of Childhood Health is a prospective study, set up to
      test the fetal insulin hypothesis, and to identify genetic polymorphisms that
      play a role in determining birthweight and early postnatal growth. We recruited
      1017 families from a postcode-defined area in central Exeter. Specific inclusion
      criteria were established to obtain a homogeneous, non-diabetic, UK Caucasian
      cohort. Detailed anthropometric measurements were taken from both parents at 28
      weeks' gestation, and from their children at birth, 12 weeks, 1 year and 2 years
      of age. Insulin and other biochemical analysis were measured in fasting parental
      samples and an umbilical cord blood sample taken at delivery. Parental and
      offspring DNA were extracted to allow molecular genetic analysis of candidate
      genes implicated in fetal growth. This comprehensive data set is available on a
      disease-free cohort, and detailed preparatory work has ensured high levels of
      quality control. The study would welcome collaboration within strict
      confidentiality rules.

PMID- 16466437
TI  - Intracellular oxidative response of human monocytes and granulocytes to different
      strains of Aspergillus fumigatus.
AB  - Aspergillus fumigatus is one of the most prevalent airborne fungal pathogens,
      causing severe and often fatal infections. Its fungal virulence factors have not
      been clearly identified. Reactive oxygen species produced by phagocytic cells are
      potent fungicides for A. fumigatus. The aim of this study was to examine the
      influence of conidia pigmentation, fungal development stage and genotype strain
      on human leucocytes oxidative response. Various A. fumigatus strains were used
      and the oxidative response was analysed by flow cytometry. A significant
      difference was observed between live- and killed-conidia. A pigmentless strain
      gave an important intracellular oxidative response compared with pigmented
      strains. But no difference was observed between strains isolated from patients
      with invasive aspergillosis (IA) and bronchial colonisation. The modification of
      healthy phagocytes' oxidative response caused by A. fumigatus components is not
      sufficient to explain the virulence of fungus and to predict an evolution of
      patients with IA.

PMID- 16466438
TI  - In vitro adhesion of Candida species to denture base materials.
AB  - Adhesion of Candida species to prosthetic acrylic resins is an essential first
      step in the pathogenesis of denture stomatitis. Data on the relative adhesion of
      pathogenic non-albicans Candida species to different denture base materials are
      sparse. The purpose of the present study was to investigate in vitro adhesion of
      C. albicans, C. glabrata, C. krusei and C. dubliniensis to four different denture
      base materials. Specimens of both heat-cured resins (Vertex(TM) Rapid Simplified
      and ProBase Hot) and cold-cured resins (Paladur A and Paladur B) were prepared
      using a novel method and the adhesion of four strains each of the foregoing
      Candida species evaluated microscopically using a soft imaging system. There was
      a significant difference in yeast adherence between Vertex and the other resins.
      Only C. glabrata attached to Vertex, while all the remainder of the tested
      species adhered to all other resins tested except ProBase, which resisted C.
      krusei adhesion. There was a significant difference in candidal adhesion between
      cold-cured and heat-cured resins for three Candida species (C. albicans, P =
      0.039; C. glabrata, P = 0.002 and C. krusei, P = 0.000). The type of denture base
      material and whether they are heat-cured or cold-cured play an important role in
      modifying candidal adhesion.

PMID- 16466439
TI  - The glyoxylate cycle enzyme activities in the pathogenic isolates of Candida
      albicans obtained from HIV/AIDS, diabetic and burn patients.
AB  - Recently it has been found that Candida albicans harbours enzymes involved in the
      glyoxylate cycle (GC), which have a role in its virulence, especially the two key
      enzymes, isocitrate lyase (ICL) and malate synthase (MS). There are however, few
      studies on the GC enzyme activities isolated in the clinical isolates. Samples
      were collected from three groups of patients namely, HIV/AIDS, diabetic and burn
      patients suffering from candidiasis at different body locations. Isolation,
      identification and the antifungal susceptibility test of all the isolates of C.
      albicans were followed by the standard techniques. Measurements of all the GC
      enzyme activities were also carried out by the standard methods. Levels of the
      principal GC enzymes showed significant changes when calculated and compared
      taking control strains of C. albicans. The activity of the two key enzymes of the
      GC, ICL and MS were significantly higher in the isolates from diabetic patients.
      No significant relationship between the drug susceptibility and the level of
      enzymes of the GC was observed. As GC activity is absent in mammalian cells, a
      specific inhibitor for the GC could be developed and these enzymes therefore can
      be used as a new antifungal target.

PMID- 16466440
TI  - The major allergen of Alternaria alternata (Alt a 1) is expressed in other
      members of the Pleosporaceae family.
AB  - There is general consensus regarding the scarce cross-reactivity existing between
      Alternaria alternata and other allergenic moulds such as Aspergillus fumigatus,
      Penicillium notatum or Cladosporium herbarum. However, A. alternata has been
      shown to have a very significant level of allergenic cross-reactivity with other
      fungi belonging to the Pleosporaceae family. To date, no biological identity or
      homologies with other proteins have been described for Alt a 1, and it remains
      unclear whether the major allergen Alt a 1 contributes to the cross-reactivity
      shown for these moulds. Specific quantification of Alt a 1 in culture filtrates
      of Stemphylium botryosum, Ulocladium botrytis, Curvularia lunata, Alternaria
      tenuissima, C. herbarum, Penicillium chrysogenum and Asp. fumigatus, and
      immunoblotting using culture filtrate extracts from the above-mentioned moulds
      and rabbit serum anti-recombinant Alt a 1 have shown significant amounts of Alt a
      1 in culture filtrates as well as antigenic components ranging from 14 to 20 kDa
      that strongly react with the specific serum for all taxonomically related species
      (Pleosporaceae family). No reactions were revealed in culture filtrates of
      Cladosporium, Penicillium and Aspergillus. These results restrict the cross
      reactivity phenomenon due to Alt a 1 to the scope of the taxonomical term of
      family.

PMID- 16466442
TI  - Utility of the oestrogen-dependent vaginal candidosis murine model in evaluating
      the efficacy of various therapies against vaginal Candida albicans infection.
AB  - The efficacy of yogurt treatment against vaginal candidosis (VC) was examined
      using an oestrogen-dependent vaginal candidosis (EDVC) murine model. The EDVC
      mouse model was constructed by inoculating mice with viable Candida albicans
      cells under pseudo-oestrus conditions. Vaginal fungal burden in the various mouse
      groups was evaluated at several time points following the induction of VC.
      Untreated and yogurt-treated naive mice exhibited background levels of VC (<6000
      CFU per mouse). Candida albicans colonisation in untreated EDVC mice was
      significantly higher (P < 0.05) than that in yogurt-treated EDVC mice at days 20
      30. Metronidazole-treated naive mice developed persistent C. albicans vaginal
      colonisation at significantly lower levels (P < 0.05) than that in untreated or
      metronidazole-treated EDVC mice. Lactobacillus was only detected in the
      reproductive tracts of yogurt-treated naive and EDVC mice. These findings suggest
      that the presence of Lactobacillus in the reproductive tract can suppress C.
      albicans growth and the antibiotics may predispose to VC.

PMID- 16466441
TI  - Intrinsic in vitro susceptibility of primary clinical isolates of Aspergillus
      fumigatus, Aspergillus terreus, Aspergillus nidulans, Candida albicans and
      Candida lusitaniae against amphotericin B.
AB  - A total of 60 clinical fungal isolates from patients without prior amphotericin B
      treatment and three control strains were evaluated for their intrinsic
      susceptibility to amphotericin B (AmB) using microdilution, Etest and disc
      diffusion assays, on three media each, Roswell Park Memorial Institute (RPMI)
      1640, Antibiotic Medium 3 (AM3) and High Resolution Medium. The fungal strains
      included isolates of Aspergillus fumigatus (n = 10), Aspergillus terreus (n =
      12), Aspergillus nidulans (n = 9), Candida albicans (n = 6) and Candida
      lusitaniae (n = 23). The A. terreus strains were significantly less susceptible
      to AmB than the A. fumigatus strains in all nine experimental settings (P-values
      ranging from 0.009 to <0.00001). The A. nidulans strains were equally susceptible
      to AmB as the A. fumigatus strains in seven of nine experimental settings and
      less susceptible in two (microdilution performed on RPMI and AM3, P = 0.01 and
      0.007). The C. lusitaniae strains were equally susceptible to AmB as the C.
      albicans strains in seven of nine experimental settings and more susceptible in
      two (microdilution and Etest, both performed on AM3, P = 0.01 and 0.0002). Thus,
      we confirmed that A. terreus is intrinsically less susceptible to AmB than A.
      fumigatus. In contrast, nine German clinical isolates of Aspergillus nidulans
      were found equally susceptible to AmB as 10 isolates of A. fumigatus.
      Furthermore, we found 23 German clinical isolates of C. lusitaniae from patients
      without prior treatment with AmB equally susceptible to AmB as C. albicans.

PMID- 16466444
TI  - Risk factors and outcome for breakthrough candidaemia in patients with cancer.
AB  - While candidaemia that develops during systemic antifungal prophylaxis or therapy
      [breakthrough (BT) candidaemia] has been reported increasingly, the risk factors
      and outcome of BT candidaemia are not yet known definitely. We evaluated a
      consecutive series of cancer patients with candidaemia at Asan Medical Center
      during 6 years to identify risk factors and outcome in BT candidaemia comparing
      with non-BT candidaemia. Fifty-four episodes of candidaemia in cancer patients
      diagnosed during this period were reviewed retrospectively. There were 10
      episodes (18.5%) of BT candidaemia in which the species distribution and
      frequency of catheter-related infection in the BT and non-BT groups were similar.
      BT candidaemia had a tendency to occur more frequently in patients with
      haematological than non-haematological diseases. Profound neutropenia and
      disseminated candidiasis were more common in the BT group; however, these
      differences were not statistically significant (P = 0.17 and 0.07 respectively).
      The duration of prior antibiotic therapy and duration of profound neutropenia
      (<100 mm(-3)) were identified as risk factors for BT candidaemia (P < 0.01 and
      0.02 respectively) in univariate analysis and the latter was the only risk factor
      in multivariate analysis. The death rates due to candidaemia were 85.7% in the BT
      group and 42.9% in the non-BT group (P = 0.08); however, BT candidaemia alone did
      not increase mortality rate.

PMID- 16466443
TI  - Deoxycholate amphotericin B and amphotericin B lipid complex exert additive
      antifungal activity in combination with pulmonary alveolar macrophages against
      Fusarium solani.
AB  - Fusarium spp. have emerged as important causes of invasive fungal infections in
      immunocompromised patients. Rabbit pulmonary alveolar macrophages (PAMs)
      exhibited fungicidal activity against conidia of Fusarium solani and achieved a
      time-dependent increase in killing. Neither deoxycholate amphotericin B (DAMB)
      nor amphotericin B lipid complex (ABLC) exerted a suppressive effect on PAMs by
      decreasing their conidiocidal activity against F. solani. On the contrary, at a
      concentration of 0.125 microg ml(-1), ABLC and, to a lesser degree, DAMB
      additively augmented the fungicidal activity of pulmonary alveolar macrophages
      against conidia of Fusarium solani.

PMID- 16466445
TI  - Dermatophytoses in monterrey, mexico.
AB  - In the present report we reviewed a total of 2397 cases of dermatophytosis from
      superficial cutaneous lesions between the years 1978 and 1990. The cases included
      were from the Department of Dermatology at the University Hospital located in the
      city of Monterrey, Mexico. A total of 726 tinea pedis, 613 tinea unguium, 441
      tinea capitis, 395 tinea corporis and 222 tinea cruris cases were observed. The
      most commonly isolated dermatophyte species was Trichophyton rubrum (45%),
      followed by Trichophyton mentagrophytes (23.7%), Trichophyton tonsurans (21%),
      Microsporum canis (7.1%) and Epidermophyton floccosum (2.5%). Less frequently we
      isolated Microsporum audouinii, Microsporum gypseum, Trichophyton violaceum and
      Trichophyton verrucosum. Most of the cases were observed in the warmest months of
      the year (from March to September), and were equally distributed in both genders,
      except for tinea cruris which was more prevalent in men (3.5 : 1 ratio).

PMID- 16466446
TI  - Genotyping of Turkish environmental Cryptococcus neoformans var. neoformans
      isolates by pulsed field gel electrophoresis and mating type.
AB  - A total of 26 environmental Cryptococcus neoformans var. neoformans strains
      isolated from 634 samples of pigeon droppings collected from 54 different
      provinces of Turkey in 1996 and 1997 were included in this study. The results of
      pulsed-field gel electrophoresis (PFGE) showed that the 26 strains could be
      separated into 24 different PFGE patterns. In a mating-type study, of 26 strains,
      20 were MATalpha, four were MATa, one was MATa/alpha and one was non-typable by
      STE20 specific primers. By the polymerase chain reaction typing, all the isolates
      were serotype A. The extensive heterogeneity among these isolates suggests that a
      single clonal population may not be present in Turkey. Additionally, the presence
      of an AMATa/DMATalpha hybrid may indicate the existence of strains that are AMATa
      mating type in Turkish environment.

PMID- 16466448
TI  - Nosocomial bloodstream infections associated with Candida species in a Turkish
      University Hospital.
AB  - In recent years, a progressive increase in the frequency of nosocomial
      candidaemia has been observed, especially among the critically ill or
      immunocompromised patients. The aim of this study was to evaluate the trend in
      incidence of candidaemia together with potential risk factors in an 850-bed
      Turkish Tertiary Care Hospital in a 4-year period. A total of 104 candidaemia
      episodes were identified in 104 patients. The overall incidence was 0.56 per 1000
      hospital admissions and the increase in incidence of candidaemia from 2000 to
      2003 was found to be statistically significant (P = 0.010). Candida albicans was
      the most common species (57.7%) and non-albicans species accounted for 42.3% of
      all episodes. The most common non-albicans Candida sp. isolated was C. tropicalis
      (20.2%) followed by C. parapsilosis (12.5%). The most frequent risk factors
      possibly associated with the candidaemia were previous antibiotic treatment
      (76.9%), presence of central venous catheter (71.2%) and total parenteral
      nutrition (55.8%). Our results show the fact that the incidence of candidaemia
      caused by non-albicans species is frequent and increasing significantly, although
      the most common isolated Candida species were C. albicans and further
      investigations are necessary to evaluate the mechanisms of increasing incidence
      of candidaemia caused by non-albicans species.

PMID- 16466447
TI  - Disseminated aspergillosis in two dogs in Israel.
AB  - Aspergillus terreus, normally a soil or plant saprophyte, causes disseminated
      systemic infection, involving primarily the skeletal and the cardiopulmonary
      system in humans and dogs.(1, 2) We describe two cases of German shepherd dogs
      that were referred to Koret School of Veterinary Medicine Teaching Hospital with
      a history of anorexia and weakness. Case 1 suffered from neurological deficits,
      paraparesis and lumbar pain whereas case 2 suffered from unilateral uveitis and
      exophthalmus. Both dogs were treated symptomatically, but deteriorated
      progressively despite therapy and were therefore euthanised. Necropsy revealed
      disseminated aspergillosis, and numerous organs had multiple, miliary, white
      yellow foci. Microscopically, these were identified as granulomas, containing
      fungal hyphae. Affected tissue included brain, heart, kidneys, spleen, lymph
      nodes and bones (case 2). Aspergillus terreus was isolated from different organs
      and from urine culture. We suggest that disseminated aspergillosis should be
      considered as a differential diagnosis in German shepherd dogs presenting with
      ocular disease, neurological deficits, spinal column pain, urinary system
      disorders, and radiographic evidence of skeletal and/or respiratory pathology.

PMID- 16466449
TI  - A case of peritonitis caused by Rhizopus microsporus.
AB  - We report a case of a 62-year-old female patient who developed peritonitis after
      receiving a renal transplant. Candida glabrata was detected and treated with
      voriconazole. As the patient did not improve under therapy, laparotomy was
      performed. Mould-like plaques were found on the peritoneum. Using culture as well
      as pan-fungal polymerase chain reaction (PCR) followed by DNA microarray
      hybridisation of the amplicon, the causative agent was identified as Rhizopus
      microsporus. Despite aggressive surgical treatment, intravenous therapy with
      amphotericin B and topical administration of Lavasept
      (polyhexamethylenbiguanide), the patient died.

PMID- 16466450
TI  - Chronic pyoderma vegetans triggered by Trichophyton mentagrophytes.
AB  - Chronic vegetating pyoderma is usually associated with staphylococci and
      streptococci. A case that started as a therapeutically resistant tinea of the
      hand caused by Trichophyton mentagrophytes is described. The vegetating skin
      lesion was associated with low immunoglobulin levels and impaired phagocytosis.
      It healed after long-term low-dose doxycycline, topical steroids and
      immunotherapy. An analogy between chronic vegetating pyoderma and recalcitrant
      tinea is discussed.

PMID- 16466451
TI  - A kerion celsi caused by Microsporum gypseum: unusual direct mycological
      examination.
AB  - A case of kerion celsi caused by Microsporum gypseum is documented. The patient
      was a 6-year-old girl with a 2-cm purulent lesion on the scalp. Direct
      mycological examination of the hair showed hyphae with extremely numerous spindle
      shaped macrospores. The species identification was confirmed by 28S ribosomal DNA
      sequencing. The presence of numerous macrospores is unusual in direct mycological
      examination, but could be an indication for M. gypseum.

PMID- 16466452
TI  - Cyclomyces tabacinus as a cause of deep tissue infection: the first case report.

PMID- 16466454
TI  - Necrotising cryptococcal vasculitis in an HIV-negative woman.
AB  - An 84-year-old woman with a past medical history significant for haemolytic
      anaemia necessitating chronic steroid therapy presented with skin induration and
      erythema initially thought to be cellulitis. After a rapid progression of
      symptoms and failure to respond to antibiotics, a clinical diagnosis of
      necrotising vasculitis was made. Necrotising cryptococcal vasculitis was
      confirmed by histopathology and culture.

PMID- 16466453
TI  - Concentric rings: an unusual presentation of tinea corporis caused by Microsporum
      gypseum.
AB  - A case of tinea corporis with the unusual presentation of concentric erythematous
      rings on the abdomen is reported. The pathogen was identified as Microsporum
      gypseum. While a number of unusual lesions have been described in M. gypseum
      infections, we are unaware of any reports on concentric rings.

PMID- 16466457
TI  - Immunohistochemical expression of Mdm2 and p53 in canine cutaneous mast cell
      tumours.
AB  - The objective of this study was to evaluate by immunohistochemical means nuclear
      reactivity for Mdm2 and p53 proteins in 71 canine cutaneous mast cell tumours.
      Detectable reactivity for Mdm2 was observed in 17 of 23 grade I tumours, 19 of 27
      grade II tumours, and 14 of 21 grade III tumours, the grading method used was
      that by Patnaik et al. [Vet. Pathol., vol. 21, 1984, p. 469]. Increased
      reactivity for Mdm2 was detected in grade III tumours compared with grade I
      tumours. In contrast to Mdm2, detectable reactivity for p53 was observed in 17
      tumours. Of 39 cases with moderate or marked Mdm2, 34 showed mild or no
      detectable p53, although only five showed moderate or marked p53. The results
      suggest that Mdm2 overexpression plays a crucial role in canine mast cell
      tumorigenesis and is consistent with the histologic grade, and its expression may
      be induced without p53 overexpression.

PMID- 16466456
TI  - In vitro binding capacity of zeolite A to calcium, phosphorus and magnesium in
      rumen fluid as influenced by changes in pH.
AB  - An in vitro experiment was designed to mimic the transport of ingested zeolite A
      in the forestomachs and proximal part of the small intestine so as to evaluate
      the binding capacity of zeolite A to Ca, P and Mg as influenced by changes in pH.
      This was done by incubation of rumen fluid solutions with and without zeolite, as
      well as varying the content of Ca and/or P. The pH was lowered by addition of HCl
      so as to mimic abomasal conditions, followed by subsequent HCO3- addition to
      mimic small intestinal pH. Rumen fluid samples were taken at strategic time
      points in the experiment. All samples were centrifuged and the supernatant
      analysed for Ca, P and Mg as indicators of the amount of unbound mineral. The
      addition of zeolite to rumen fluid solutions reduced the amount of supernatant Ca
      and Mg at rumen pH, whereas the level of P was not reduced. After adding HCl, a
      large proportion of the zeolite-bound Ca and Mg was released, increasing
      supernatant Ca and Mg levels; whereas, HCl addition led to a profound drop in
      supernatant P in zeolite samples, indicating binding of P. A low level of
      supernatant P was maintained after HCO3- addition. Neutralization by HCO3- led to
      a zeolite-induced drop in supernatant Ca and Mg. The reduction in supernatant Ca
      observed in the present study concurs well with the theoretical rationale of
      prepartum zeolite supplementation in milk fever prevention. Furthermore, the
      apparent binding of P by the zeolite may also contribute because of the
      connection between the calcium and phosphorus homeostasis. The zeolite-induced
      reduction in supernatant Mg indicates that zeolite supplementation should
      probably be avoided in Mg-deficient herds unless Mg supplementation is initiated.

PMID- 16466458
TI  - Severe combined immunodeficiency in a Fell pony foal.
AB  - Five days after birth of a viable Fell pony filly, yellow watery diarrhoea
      appeared without any signs of systemic disease. Four days later the diarrhoea
      ceased. On 11th day, the animal showed apathy, and a few days later, the foal was
      very lethargic, suffered from muscular weakness and severe watery diarrhoea that
      reappeared. The illness did not respond to therapy. At the age of 21 days the
      filly spontaneously died under symptoms of intestinal colic and pneumonia.
      Haematological examinations revealed lower numbers of erythrocytes as well as non
      selective lymphopenia. Phagocytic activity was slightly increased, lymphocyte
      activity was inhibited. Histopathology showed severe alteration of the lymphatic
      organs. T and B lymphocytes and antigen-presenting macrophages were not arranged
      in characteristic areas, and the quantity of these cells was lower than would be
      expected. Histopathological changes in lymphatic organs resembled those described
      in the literature as severe combined immunodeficiency.

PMID- 16466459
TI  - Cutaneous plasmacytoma in three golden hamsters (Mesocrietus auratus).
AB  - Spontaneously occurring cutaneous tumours in three golden hamsters were
      characterized using histological, immunohistochemical and ultrastructural
      methods. Histologically, the tumours were composed of sheets of round to oval
      plasmacytoid cells with eccentrically placed nuclei. Tissue sections were weakly
      positive for anti-B lymphocyte antigen (BLA) staining. Ultrastructurally, large
      amounts of rough endoplasmic reticulum in the cytoplasm were observed. BLA
      positivity and characteristics of ultrastructure showed the plasma cell origin.

PMID- 16466460
TI  - A case of suspected lysosomal storage disease in a neonatal Japanese black calf.
AB  - A 5-day-old Japanese black calf was necropsied and intracytoplasmic vacuolations
      were histologically observed in many tissues. In the central nervous system,
      intracytoplasmic inclusions and vacuoles were found in neuronal cells.
      Intracytoplasmic inclusions were more conspicuous in the nuclei containing large
      nerve cells, especially in the brain stem and spinal cord. These inclusions were
      stained weak positive to positive with alcian blue, Giemsa, Luxol fast blue and
      periodic acid-Schiff stains but not with oil red O. Ultrastructurally, neuronal
      inclusions were observed in lysosomes and consisted of an amorphous electron
      dense substance and occasional membranous structures. These findings seem to
      differ from the cases of bovine lysosomal diseases that have been reported, and
      this case may be another type of lysosomal storage disease.

PMID- 16466461
TI  - Chronic progressive autonomic dysfunction in a dog.
AB  - A 3.5-year-old intact male American Pit Bull was presented because of urinary
      incontinence and dysuria. Constipation, followed by diarrhoea, ocular
      disturbances and finally regurgitation developed over the next 4 years. Autonomic
      dysfunction was evidenced by clinical presentation, as well as positive
      ophthalmic pilocarpine test and subnormal Schirmer tear test. Diagnosis, however,
      was established through histopathological and immunohistochemical examination.
      Lesions attributable to inflammatory degenerative neuropathy of the autonomic
      ganglia, which represents one of the various types of human autonomic failure,
      were detected.

PMID- 16466462
TI  - Long-term measurement of gastric motility using passive telemetry and effect of
      guar and cellulose as food additives in dogs.
AB  - The suitability of passive telemetry for long-term measurements of gastric
      motility in two groups of dogs with different body weights, four Beagles and four
      Labrador Retrievers, was investigated. An intra-abdominal measuring device, with
      a pressure sensor and electrodes within the gastric wall, allowed the continuous
      recording of the intensity and frequency of contractions simultaneously with an
      electromyogram (EMG). In fasting dogs a typical inter-digestive motility cycle
      was reproducible. Within 15 min of feeding the integral of the pressure curve
      increased significantly, reaching its maximum 30-45 min post-prandially. The peak
      frequency also significantly increased immediately after feeding, reaching the
      maximum of 22 contractions per 5 min. The post-prandial motility patterns of the
      groups were significantly different. The pressure amplitudes of the Labradors
      were significantly higher and the peak frequencies significantly lower than the
      Beagles. The addition of guar to the food (2.5% or 5%) leads to a significant
      reduction of the intensity of the antral contractions, whereas the frequency was
      hardly affected. In comparison, the effect of cellulose, as a food additive (2.5%
      or 5%), was rather modest. The intensity of the post-prandial contractions,
      influenced by cellulose, was significantly increased in Beagles, but was
      decreased in Labradors. Passive telemetry has been proven to be a suitable method
      for the long-term investigation of the physiological gastric motility and the
      effect of food additives. The measuring device was still functional after removal
      8 weeks later.

PMID- 16466464
TI  - Clinical pharmacokinetics of anti-angiogenic photodynamic therapy with
      benzoporphyrin derivative monoacid ring-A in dogs having naturally occurring
      neoplasms.
AB  - The aim of this study was to examine the pharmacokinetics of clinically applied
      benzoporphyrin derivative monoacid ring-A (BPD-MA; Verteporfin), a second
      generation photosensitizer, during a trial of photodynamic therapy (PDT) in nine
      dogs having naturally occurring neoplasms. After injecting BPD-MA at 0.5 mg/kg
      intravenously, its mean half-life (t1/2) was found to be 8.14 +/- 5.34 h, mean
      clearance (Cl) 35.13 +/- 9.62 ml/(h kg), the mean value of the volume of
      distribution (Vc) 0.08 +/- 0.01 l/kg and the mean steady state volume of
      distribution (Vss) 0.38 +/- 0.31 l/kg respectively. With the exception of a
      transitional increase in serum alkaline phosphatase activity, no other clinical
      abnormalities were observed. The t1/2 in dogs with naturally occurring tumours
      was longer than that in humans, but similar to that in rats. The values of Cl and
      Vss in dogs having naturally occurring neoplasms were lower than those in humans.
      It is suggested that the pharmacokinetics of BPD-MA in tumour-bearing dogs would
      be helpful in determining the protocol of a short drug-light interval PDT with
      BPD-MA that mainly targets the tumour vasculature.

PMID- 16466463
TI  - Effect of anticholinergics (atropine, glycopyrrolate) and prokinetics
      (metoclopramide, cisapride) on gastric motility in beagles and labrador
      retrievers.
AB  - The effect of atropine, glycopyrrolate, metoclopramide and cisapride on the
      antral motility was investigated in eight dogs (four Beagles and four Labradors)
      using passive telemetry. Both anticholinergics induced a pronounced and lasting
      reduction of the intensity and frequency of the contractions. A definite dose
      related inhibition of the antral motility was seen in Beagles, similar for both
      active substances. Low doses of atropine (0.02 mg/kg BW i.m.) and glycopyrrolate
      (0.005 mg/kg BW i.m.) completely inhibited the gastric motility for at least 30
      min, whereas higher doses (0.04 or 0.01 mg/kg BW) caused a cessation of activity
      for more than 3 h. In Labradors, the effects of both active substances were not
      so dose related and the effect of glycopyrrolate lasted at least 6 h, whereas the
      effect of atropine gradually decreased after 3 h. A distinct breed difference
      regarding the effect of the two prokinetics on the antral motility was also
      observed. In Beagles, the prokinetics, at a low dose (metoclopramide 0.3 mg/kg
      BW, cisapride 0.2 mg/kg BW), resulted in a significant increase in the amplitude
      integral. Higher doses (metoclopramide 0.6 mg/kg BW, cisapride 0.5 mg/kg BW) also
      increased the integrals of the pressure profiles, but significantly less than
      with the lower doses. In Labradors, both medications, mainly at higher doses,
      resulted in an increase of the contraction amplitudes. The low dose had no
      (cisapride) or only a transient effect (metoclopramide). The frequency of the
      antral contractions was not at all influenced by cisapride, and only in Beagles
      metoclopramide resulted in a dose-related increase. It is not clear if the
      different results in Labradors and Beagles are because of breed or body weight.

PMID- 16466465
TI  - Improving the dietary patterns of adolescents using a computer-based approach.
AB  - The Centers for Disease Control and Prevention (CDC) recently reported that 16
      33% of children and adolescents in the United States are overweight or obese,
      making this the number one nutritional disease of this group. The prevalence
      appears to be increasing annually, as are the associated consequences. Moreover,
      the CDC estimates that less than 50% of adolescents are physically active on a
      regular basis. In order to improve the health of these individuals, an
      intervention must be focused to modify these behaviors. Facilitating the
      understanding of proper nutrition and need for physical activity among
      adolescents will likely prevent health problems such as overweight and obesity
      and the development of chronic diseases later in life. Despite these concerns,
      adolescents remain one of the most underserved populations in terms of preventive
      services. In the past, health education interventions have shown increases in
      knowledge; however, the ultimate goal of these programs is to positively impact
      behavior. To accomplish this, we must focus on the learning styles of "today's"
      adolescents. Computer-based interventions allow for individualized strategies to
      promote healthy lifestyles. A computer-based intervention program has the
      potential to elicit a greater behavior change in comparison to a traditional
      didactic intervention program.

PMID- 16466467
TI  - Medication adherence among adolescents in a school-based health center.
AB  - School-based health centers are an integral part of the health care delivery
      system for low-income children. Medication adherence for these patients may be
      challenging because the student is often responsible for bringing home the
      prescription and receiving the instructions. This study assesses medication fill,
      initiation, and adherence rates among adolescents in a school-based health center
      to identify major barriers to medication compliance. Students enrolled in a
      school-based health center, >or=10 years old, able to read and write English, and
      whose parent had provided consent for participation, were eligible for the study.
      Eligible students who received a prescription from the health center were invited
      to return to the clinic a week later to complete a questionnaire (with verbal
      assent). Primary outcome measures included medication fill rates, medication
      initiation rates, medication adherence rates, and reasons for nonadherence.
      Eighty-one students completed the questionnaire: 45 students (55.6%) filled their
      prescription. Of the students who filled their prescriptions, 75.6% reported
      always taking their medication at the appropriate time, 22.2% reported sometimes
      forgetting to take their medication, and 2.2% reported never taking the
      medication. However, many discrepancies were found between reported medication
      taking behavior and the instructions provided to the student. Medication fill,
      initiation, and adherence rates among students receiving prescriptions for
      medications in school-based health centers are suboptimal. Interventions that
      address key identified barriers need to be developed and evaluated in order to
      achieve optimal fill and adherence rates.

PMID- 16466466
TI  - Comparisons between Thai adolescent voices and Thai adolescent health literature.
AB  - Thai adolescents are hesitant to openly talk to adults; however, they are avid
      users of the Internet. In 2002, faculty of the Boromarajonani College of Nursing,
      Nopparat Vajira, Thailand, established a webboard to reach out to high school
      students for questions and answers on adolescent health. Adolescents pose health
      questions, which are answered by nursing faculty and students. A total of 106
      questions were selected for content analysis. Thai adolescent studies for the
      years 1992 to 2004 were identified from searches of CINAHL, ERIC, MEDLINE, and
      PsycINFO databases. The selection criteria required that chosen articles have a
      Thai adolescent health focus, be written in English, and be retrievable. Of the
      68 citations identified, 23 studies met inclusion criteria. Content of the Thai
      adolescent webboard was compared with a content analysis of the retrieved Thai
      adolescent research. Physiological development, sexuality, and risky behaviors
      were common literature themes, whereas Thai adolescents expressed concerns about
      love and dating relationships. Parenting and parent-child relationships were
      discussed on the webboard but not in the literature. Analysis of the mental
      health revealed differences between the literature that covered psychosocial
      change, and the webboard questions concerned with body image, the need for
      emotional support, and satisfaction and conflicts of friendship. It is
      recommended that investigators consider incorporating adolescents as research
      team participants, particularly as they examine mental health promotion,
      adolescent and family relationships, and concerns of Thai adolescents.

PMID- 16466468
TI  - Applying the School Health Index to a nationally representative sample of
      schools.
AB  - The School Health Index (SHI) is a self-assessment and planning tool that helps
      individual schools identify the strengths and weaknesses of their health policies
      and programs. To determine the percentage of US schools meeting the
      recommendations in the SHI, the present study analyzed data from the School
      Health Policies and Programs Study (SHPPS) 2000. The SHPPS 2000 data were
      collected through computer-assisted personal interviews with faculty and staff in
      a nationally representative sample of schools. The SHPPS 2000 questions were then
      matched to SHI items to calculate the percentage of schools meeting the
      recommendations in 4 areas: school health and safety policies and environment,
      health education, physical education and other physical activity programs, and
      nutrition services. Although schools nationwide are meeting a few SHI items in
      each of these areas, few schools are addressing the entire breadth of items. A
      more coordinated approach to school health would help schools reinforce health
      messages.

PMID- 16466469
TI  - Definition and outcome of a curriculum to prevent disordered eating and body
      shaping drug use.
AB  - Almost one half of male and female students participate in high school-sponsored
      athletics, and high school also is a time when classroom health promotion
      curricula are less effective. The Athletes Training and Learning to Avoid
      Steroids is a sport team-centered drug-use prevention program for male high
      school athletes, which has been shown to reduce alcohol and illicit drug use.
      Just as anabolic steroid use is associated with male athletes, female sport
      participants may be at a greater risk for disordered eating and body-shaping drug
      use. Extending sport team-centered programs to young women athletes required
      defining and ranking factors related to developing those harmful behaviors.
      Survey results from a cross-sectional cohort of female middle and high school
      student athletes were used to identify and prioritize potential curriculum
      components, including mood and self-esteem, norms of behavior, perceptions of
      healthy body weight, effects of media depictions of women, and societal pressures
      to be thin. The derived sport team-centered program was prospectively assessed
      among a second group of female student athletes from 18 high schools, randomized
      to receive the intervention or the usual care control condition. The Athletes
      Targeting Healthy Exercise and Nutrition Alternatives (ATHENA) intervention is a
      scripted, coach-facilitated, peer-led 8-session program, which was incorporated
      into a team's usual training activities. The ATHENA program significantly altered
      the targeted risk factors and reduced ongoing and new use of diet pills and body
      shaping substances (amphetamines, anabolic steroids, and sport supplements).
      These findings illustrate the utility of a structured process to define
      curriculum content, and the program's positive results also confirm the sport
      team's potential as a vehicle to effectively deter health-harming behaviors.

PMID- 16466470
TI  - An integrated curriculum approach to increasing habitual physical activity in
      children: a feasibility study.
AB  - A relatively new concept is that of "integrating" physical activity throughout
      the school curriculum, thereby teaching children about lifestyle physical
      activity in a variety of contexts. One method by which this may be achieved is by
      utilizing pedometers as a motivational and educational tool for measuring
      accumulated physical activity. No research is available that shows in-depth
      integration of physical activity into the curriculum or that investigates the
      efficacy of pedometer use for this purpose. The purposes of this study were to
      (1) design and implement a 4-week elementary school curriculum unit, based around
      pedometer walking and (2) quantify, using pedometry, the physical activity levels
      of children (N = 78) prior to, and during, the unit implementation. Results
      showed that more than one half of the participants were achieving >15,000 steps
      daily, and children were significantly more active on weekdays than weekends (p =
      .0001). Boys were more active than girls at baseline (p = .01) and during
      intervention weekdays (p = .03). Differences between baseline and intervention
      weekdays were nonsignificant for the complete sample; however, significant
      increases in step counts were observed when the children with low activity
      levels, especially females, were examined separately. Overall, the integration of
      physical activity using pedometer-based activities is feasible. However, any
      increases in activity may be restricted to children who are least active.

PMID- 16466471
TI  - Internet versus paper mode of health and health behavior questionnaires in
      elementary schools: asthma and fruit as examples.
AB  - The Internet has become an inevitable tool for collecting health and health
      behavior questionnaires. This study compared the feasibility, presence of score
      differences, and subjective evaluations by children between Internet and
      identical paper (asthma/fruit) questionnaires in elementary schools. A randomized
      crossover design was applied, with children starting with one administration mode
      before completing (5 minutes later) the other mode. Ten Dutch elementary schools
      with 270 school children (fifth grade, 10-12 years) were approached to
      participate. Response was 92%. The Internet mode had significantly less
      missing/nonunique answers than the paper mode (p < .01). The completion times did
      not differ significantly between the Internet and the paper mode. Except for
      perceived self-efficacy to eat sufficient fruit (p < .05), no differences in the
      asthma and fruit scores were found when comparing between the 2 modes. All
      variables showed strong intraclass correlation coefficients (166 >or= 0.64)
      between modes. Most items had good to very good agreement (kappa 0.61-0.95). The
      percentages for global and exact agreement ranged per item from 61.3 to 100. Most
      children preferred the Internet mode on "general preference" and "ease of use"
      aspects but rated no preference on "understandability." The majority rated the
      evaluation aspects of the Internet mode positively. Thus, Internet administration
      of a health and health behavior questionnaire is feasible at elementary schools,
      gives comparable responses, and is well accepted and preferred by children
      compared to the paper version. Therefore, it is recommended to use Internet as a
      tool in health and health behavior research among children.

PMID- 16466472
TI  - Editorial: Should studies without ethical permission be published in JCN?

PMID- 16466474
TI  - The Acute Care Nurse Practitioner: challenging existing boundaries of emergency
      nurses in the United Kingdom.
AB  - AIM: This study explored the opinions of nurses and doctors working in emergency
      departments towards the development of the Acute Care Nurse Practitioner service
      in the United Kingdom. BACKGROUND: Studies carried out in the United States and
      Canada suggest that the Acute Care Nurse Practitioner can have a positive impact
      on the critically ill or injured patients' experiences in the emergency
      department. This role is well developed in the United States and Canada, but is
      still in its infancy in the United Kingdom. DESIGN AND METHODS: A descriptive,
      exploratory design incorporating questionnaires (n = 98) and semi-structured
      interviews (n = 6) was employed. The sample included nurses and doctors from
      seven emergency departments and minor injury units. RESULTS: Respondents felt it
      was important for the Acute Care Nurse Practitioner to have obtained a specialist
      nurse practitioner qualification and that the Acute Care Nurse Practitioner
      should retain a clinical remit. While participants seemed comfortable with nurses
      undertaking traditional advanced skills such as suturing, reluctance was
      displayed with other advanced skills such as needle thoracocentesis. Three main
      themes were identified from the interviews: inter-professional conflict, autonomy
      and the need for the Acute Care Nurse Practitioner. DISCUSSIONS: Doctors were
      reluctant to allow nurses to practise certain additional advanced skills and
      difficulties appear to be centred on the autonomy and other associated inter
      professional conflicts with the role of the Acute Care Nurse Practitioner.
      CONCLUSION: Nurses and doctors identified a need for the Acute Care Nurse
      Practitioner, but the blurring of boundaries between doctors and nurses can
      result in inter-professional conflict unless this is addressed prior to the
      introduction of such advanced practitioners. Relevance to clinical practice. As
      the role of the emergency nurse diversifies and expands, this study re-affirms
      the importance of inter-professional collaboration when seeking approval for role
      expansions in nursing.

PMID- 16466475
TI  - The health-promoting school: what role for nursing?
AB  - AIM: To review the existing literature on health-promoting schools and put
      forward recommendations for continuing progress. BACKGROUND: The World Health
      Organisation's Ottawa Charter for Health Promotion in 1986 sought to create a
      framework for health promotion action that conveyed the notion of capacity
      building as it related to specific settings. It provided the catalyst from which
      the health-promoting school movement emerged, against the backdrop of health
      professionals adapting to the changing needs and demands of clients and the
      evolving social context of the communities in which they live. Since then, the
      international health-promoting school movement has been one of the most
      successful of the settings-based projects and has expanded considerably over
      recent years. METHOD: An extensive review of available health-promoting school
      related literature provides the basis for critical discussion and
      recommendations. FINDINGS: Traditionally, the school nursing movement has
      provided the backbone of nursing-related health promotion activity in the school
      setting. The literature, however, is generally critical of its contribution over
      the years - especially as its role is mainly confined to a 'conventional' health
      education function and has little to do with health-promoting school projects.
      There are more and more calls now for the school nursing service to either re
      evaluate its function and processes or be devolved back into a broader primary
      health care practitioner role. CONCLUSION: Nurses should view the health
      promoting school movement as another opportunity to embrace evolving broad-based
      health promotion concepts truly, as a means to forge and own their own health
      agenda and also as a means to move beyond a traditional reliance on a limited
      health education role. Schools also need to adapt and expand their efforts to
      focus on health promotion activities, in collaboration with the ever-widening
      community networks of health and social agencies. This requires the commitment of
      all healthcare professional groups. Nurses who practice in all settings, and not
      just school nurses, should be aiming to initiate and promote radical health
      promotion reform as set out in the health-promoting school movement. RELEVANCE TO
      CLINICAL PRACTICE: If health professionals wish to be at the forefront of current
      health-promoting school strategies they must embrace the radical health promotion
      reforms that are emerging from the current literature and put forward in this
      article. Building such group capacity, through developing social interaction,
      cohesion, participation and political action can only benefit the community at
      large and further emphasize the health promotion role of nursing. The health
      promoting school movement is truly an international concept and, as such,
      deserves a concerted nursing representation and resourcing well beyond its
      current commitment.

PMID- 16466476
TI  - Nurse consultants: organizational influences on role achievement.
AB  - AIMS: This paper reports on organizational influences on nurse consultant post
      holders. The influence of individual characteristics has been the subject of
      another paper. BACKGROUND: Nurse consultant posts were set up in the United
      Kingdom from the late 1990s onwards and, therefore, there has been little
      opportunity to report on evaluations of these innovative initiatives. DESIGN: A
      cross-sectional design, using a convenience sample, was adopted. METHODS: Ten
      nurse consultants working in a variety of settings and specialties participated
      in in-depth, tape-recorded interviews. The data were analysed using the Framework
      approach. FINDINGS: Support systems were important influences on nurse
      consultants' role achievement levels. These took the form of internal trust
      networks, nurse consultant forums and links with higher education institutions.
      Post holders both gave and received support and acted to empower other nurses.
      Thus, relationships were vital to successful role integration. The culture and
      structures of the National Health System were also a powerful influence in terms
      of local and national modernization policies, and participants had to be careful
      in their choice of strategies to deal with the traditional medically dominated
      culture. CONCLUSIONS: The new nurse consultant role is challenging and
      innovative, but a major area of contention is how much post holders are expected
      to take on work previously done by doctors rather than developing their nursing
      role. Organizational support and commitment are needed if nurse consultants are
      to maximize the benefits of this innovation. RELEVANCE TO CLINICAL PRACTICE: The
      findings show that new nursing roles are not always easily accepted in
      multidisciplinary settings and that holders of such post need to have the
      appropriate previous knowledge, skills and personal characteristics, as well as
      the ability to negotiate their way through organizational influences.

PMID- 16466477
TI  - Registered Nurses working together with family members of older people.
AB  - AIM: The aim of the study was to reach a more profound understanding, through
      looking at nurses' working situation, of those factors that influence how nurses
      are able to work together with family members of older people living in nursing
      homes or similar facilities. BACKGROUND: Working with the care of older people as
      a Registered Nurse provides a varied job with many challenges. Nurses have to co
      operate with family members of those in community health care. Co-operation is
      important and necessary for all involved. DESIGN: Nurses working in elder care in
      a geographically defined area received a questionnaire with three open-ended
      questions, on the difficulties and/or problems involved with working together
      with family members, and the positive or negative aspects of this co-operation.
      METHODS: Analysis was carried out using the latent content analysis method.
      RESULTS: Three themes, problems within the system, interaction with families and
      caring in nursing work, are presented with categories and their subcategories.
      The nurses wanted their superior to be a nurse so that their working situation
      would be better understood. Appreciation from their superior and family members
      was also a very important part of their work as nurses in community health care.
      The frequent changes and the lack of time in the work of elder care often put
      nurses under considerable psychological pressure. For the most part family
      members are a resource for the elder, but sometimes they will avoid contact,
      which will make co-operating difficult. CONCLUSION: Registered Nurses and family
      members are dependent on each other in their care of the elder. Relevance to
      clinical practice. More attention should be paid to the working situation of
      Registered Nurses in community health care, and their ability to work together
      with family members of older people.

PMID- 16466478
TI  - Psychological approaches to chronic pain management: part 1.
AB  - AIMS AND OBJECTIVES: The aim of this paper is to provide an overview of the
      theoretical basis and application of psychological interventions used in the
      management of chronic pain. In doing this, psychological factors mediating pain
      and disability will also be reviewed. BACKGROUND: A biopsychosocial model of
      chronic pain is widely purported and pain management is often based upon
      cognitive-behavioural principles as psychological factors meditating pain and
      disability have been found to include emotional, cognitive and behavioural
      components. CONCLUSIONS: This paper provides support for a biopsychosocial model
      of and for the effectiveness and efficacy of psychological interventions for the
      management of chronic pain conditions. RELEVANCE TO CLINICAL PRACTICE: The
      application of psychological approaches to chronic pain management is reviewed
      and discussed. The way in which psychological approaches may be integrated
      specifically into nursing management of chronic pain is discussed in a later
      paper.

PMID- 16466479
TI  - Comparison between direct humidification and nebulization of the respiratory
      tract at mechanical ventilation: distribution of saline solution studied by gamma
      camera.
AB  - AIM: To study the effectiveness of this procedure, an intra-individual pilot
      study comparing the distribution of an instilled radiolabelled saline solution
      and an inhaled nebulized radiolabelled saline solution was performed using a
      scintigraphic technique. BACKGROUND: In patients treated with mechanical
      ventilation, we have routinely used instillation of saline solution in the
      endotracheal tube before suctioning with the aim of softening mucus and
      facilitating removal of secretions. In our experience, the effectiveness of this
      procedure is doubtful. It may also have adverse effects. METHODS: Nine patients
      on mechanical ventilation were examined with Single Photon Emission Computed
      Tomography on the same occasion using both humidification methods. The entire
      examination was carried out with the patient kept in a constant position in
      relation to the gamma camera, thereby allowing subtraction of the first
      registration from the second registration and subsequent evaluation and digital
      comparison of the two humidification methods. RESULTS: Most of the instilled
      fluid goes to the posterior portion of the right lower pulmonary lobe. Compared
      with direct instillation, nebulized solution is more uniformly distributed
      between and within the lungs. With nebulization, distribution is less influenced
      by gravitation than with instillation. The aerosol reaches the periphery of the
      lung to a larger extent. CONCLUSIONS: Through the use of an aerosol with specific
      size characteristics, it may be possible to optimize the distribution of a fluid
      in the respiratory tract and achieve a more homogenous humidification. It is
      recommended to replicate the study using 25 subjects. Relevance to clinical
      practice. Direct instillation of saline should not be used with mechanical
      ventilation.

PMID- 16466480
TI  - Documenting the cognitive status of hip fracture patients using the Short
      Portable Mental Status Questionnaire.
AB  - AIMS AND OBJECTIVES: The aim of this study was to describe how nurses document
      their subjective assessment of the patients' cognitive status in the patients'
      records and to compare this documentation with an assessment made using a
      validated evaluation instrument in older patients with a hip fracture.
      BACKGROUND: There are indications that older people with a hip fracture and
      impaired cognitive ability do not receive optimal care and that they suffer from
      a disproportionately high number of complications. Preventing and rapidly
      detecting confusion is probably an effective strategy for improving care for
      these patients. To be able to prevent care-related complications and plan for
      future nursing and medical care, it is necessary to identify patients with
      impaired cognitive ability. DESIGN: Clinical trial including 362 patients.
      METHODS: The patients' cognitive function was assessed by a research nurse using
      a validated instrument, the Short Portable Mental Status Questionnaire, and an
      independent subjective assessment was made by a ward nurse. The agreement between
      these assessments was analysed. RESULTS: An assessment of cognitive function by
      the ward nurse was lacking in 12% of the patients. The assessment made by the
      nurses did not correspond to the level of orientation according to Short Portable
      Mental Status Questionnaire in 24% of the patients. In the vast of majority of
      these cases, the patients were documented as being cognitively alert although
      they were cognitively impaired according to the Short Portable Mental Status
      Questionnaire. Among the patients who were cognitively oriented according to the
      Short Portable Mental Status Questionnaire, the nurses' assessment identified 97%
      as oriented, but among the patients with impaired cognitive ability according to
      the Short Portable Mental Status Questionnaire, only 58% were identified as being
      cognitively impaired by the ward nurses. CONCLUSIONS: An assessment of cognitive
      function is still lacking in nursing records for a substantial number of older
      people with a hip fracture and cognitive dysfunction is frequently underdiagnosed
      in routine health care. RELEVANCE TO CLINICAL PRACTICE: Patient care could be
      improved if the patients' cognitive function was assessed regularly and
      objectively by means of a validated evaluation instrument.

PMID- 16466481
TI  - The power of hope: patients' experiences of hope a year after acute spinal cord
      injury.
AB  - AIMS AND OBJECTIVES: The aim of this present study was to explore patients'
      experiences of the meaning they attribute to hope and hoping a year after acute
      spinal cord injury. BACKGROUND: Nursing literature is pointing towards the
      importance of having hope for a healthful living. However, the concept of hope
      has preliminarily been defined in an abstract and general way and is therefore
      difficult to grasp. DESIGN AND METHODS: This qualitative study has a longitudinal
      and descriptive-explorative design. Data were collected by personal interviews (n
      = 10) one year after acute spinal cord injury. A phenomenological-hermeneutic
      approach, based on the philosophy of Ricoeur, was used to extract the essences of
      the patients' experiences. RESULTS: The findings resulted in one main
      interpretation: 'The Power of Hope', and two sub-themes: 'Will, Faith and Hope'
      and 'Hoping, Struggling and Growing'. The power of hope was interpreted as the
      individual having experienced the meaning a year after the injury, mainly
      expressed through will power. CONCLUSIONS: This study shows that experiences of
      hope were important to all participants, providing energy and power to the
      process of struggling because hope is necessary for further progress and personal
      development. Relevance to clinical practice. Nursing interventions should be
      mainly directed towards emotional and motivational strategies to promote the will
      power and personal growth through learning experiences.

PMID- 16466482
TI  - 'The intruder': spouses' narratives about life with a chronically ill partner.
AB  - AIM: The aim of this study was to illuminate the meaning of middle-aged spouse's
      experiences of living with a chronically ill partner. A purposive sample of four
      female spouses was selected for interviews using a narrative approach.
      BACKGROUND: When someone is diagnosed with a chronic illness, it is easy to
      understand that a considerable number of devastating consequences follow, both
      for the afflicted as well as for the family. Families often feel neglected and
      that their problems and needs are underestimated, if they do not personally draw
      attention to this fact. METHODS: A phenomenological hermeneutic method, inspired
      by the philosophy of Ricoeur, was used when interpreting the interview text.
      RESULTS: The experiences of spouses living with a chronically ill partner often
      brought a feeling of detachment from their partner's lives. The women experienced
      changes in their relationships because of their partners' disabilities; they had
      emotions of loneliness, despite living together as a couple. Through their
      actions, the women sought reassurance and support in order to maintain a
      meaningful partnership with their spouses and this is expressed in three themes:
      feelings of limitation, the struggle of everyday life and a striving for
      normalization. CONCLUSIONS: Middle-aged women living with a chronically sick
      partner are still of an active disposition and regard themselves as still being
      in mid-life. They wish to be loved as a wife and not as a care provider.
      RELEVANCE TO CLINICAL PRACTICE: The findings from this study can help increase
      the knowledge and understanding of the problems and concerns encountered by
      middle-aged spouses living with chronically ill partners and can be useful in the
      education and supervision of nurses and in relationship with relatives.

PMID- 16466483
TI  - Social capital, age and religiosity in people who are lonely.
AB  - AIMS AND OBJECTIVES: The aims of the study were to (i) investigate age and
      loneliness, (ii) investigate the association between religiosity and loneliness,
      and (iii) and explore the relationship between social capital and loneliness.
      BACKGROUND: Loneliness is the subjective experience of social isolation and is a
      risk factor for a wide range of health problems including heart disease and
      depression. Poor self-rated health, domestic violence and poor economic
      conditions are associated with greater loneliness. DESIGN: The study was a cross
      sectional survey of a random sample of adults aged 18 years and over. METHODS: A
      random sample of 1289 subjects was interviewed by computer-assisted telephone
      interviewing. This interview included the Loneliness Scale and items from the
      Social Capital Module of the General Household Survey. FINDINGS: Loneliness is
      more common in men and people without strong religious beliefs. An income
      loneliness gradient is evident. Little support was found for the association
      between social capital and loneliness. CONCLUSION: The prevalence of loneliness
      is relatively stable in this population. Loneliness is linked to income and
      unemployment and as such pathways between socio-economic factors, loneliness and
      health need to guide interventions and future research. RELEVANCE TO CLINICAL
      PRACTICE: Loneliness is linked to a range of social and economic factors. Current
      Health Visiting practice recognizes the importance of tackling the effects of
      poverty and social deprivation and places community building at the core of much
      Health Visiting practice. This broad community level approach can usefully
      transfer into all community nursing and health promotion activity.

PMID- 16466484
TI  - Patterns and frequency of anxiety in women undergoing gynaecological surgery.
AB  - AIMS: Within a gynaecological surgical setting to identify the patterns and
      frequency of anxiety pre- and postoperatively; to identify any correlation
      between raised anxiety levels and postoperative pain; to identify events, from
      the patients' perspective, that may increase or decrease anxiety in the pre- and
      postoperative periods. BACKGROUND: It is well documented that surgery is
      associated with increased anxiety, which has an adverse impact on patient
      outcomes. Few studies have been conducted to obtain the patient's perspective on
      the experience of anxiety and the events and situations that aggravate and
      ameliorate it. METHOD: The study used a mixed method approach. The sample
      consisted of women undergoing planned gynaecological surgery. Anxiety was
      assessed using the State Trait Anxiety Inventory. Trait anxiety was measured at
      the time of recruitment. State anxiety was then assessed at six time points
      during the pre- and postoperative periods. Postoperative pain was also measured
      using a 10 cm visual analogue scale. Taped semi-structured telephone interviews
      were conducted approximately a week after discharge. RESULTS: State anxiety rose
      steadily from the night before surgery to the point of leaving the ward to go to
      theatre. Anxiety then increased sharply prior to the anaesthetic decreasing
      sharply afterwards. Patients with higher levels of trait anxiety were more likely
      to experience higher levels of anxiety throughout their admission. Elevated
      levels of pre- and postoperative anxiety were associated with increased levels of
      postoperative pain. Telephone interviews revealed a range of events/situations
      that patients recalled distressing them and many were related to inadequate
      information. CONCLUSION: This study found higher rates of anxiety than previously
      reported and anxiety levels appeared raised before admission to hospital. This
      has important clinical and research implications. RELEVANCE TO CLINICAL PRACTICE:
      Patients with high levels of anxiety may be identified preoperatively and
      interventions designed to reduce anxiety could be targeted to this vulnerable
      group. Patient experiences can inform the delivery of services to meet their
      health needs better.

PMID- 16466485
TI  - Osteoporosis in older Chinese men: knowledge and health beliefs.

PMID- 16466486
TI  - Translation and validation of the Chinese version of the Charing Cross Venous
      Ulcer Questionnaire.

PMID- 16466487
TI  - Evaluation of an education programme for Chinese women receiving internal
      radiation for uterine cervical cancer.

PMID- 16466489
TI  - Commentary on Celik S, Oztekin D, Akyolcu N and Issever H (2005) Sleep
      disturbance: the patient care activities applied at the night shift in the
      intensive care unit. Journal of Clinical Nursing 14, 102-106.

PMID- 16466488
TI  - A comparison of preceptor and preceptee's perceptions of how the preceptor's role
      is operationalized.

PMID- 16466490
TI  - Commentary on Li H (2005) Hospitalized elders and family caregivers. Journal of
      Clinical Nursing 14, 3-8.

PMID- 16466491
TI  - Commentary on Hekkink CF, Wigersma L, Yzermans CJ and Bindels PJ (2005) HIV
      nursing consultants: patients' preferences and experiences about the quality of
      care. Journal of Clinical Nursing 14, 327-333.

PMID- 16466492
TI  - Commentary on McKain S, Henderson A, Kuys S, Drake S, Kerridge L and Ahern K
      (2005) Exploration of patients' needs for information on arrival at a geriatric
      and rehabilitation unit. Journal of Clinical Nursing 14, 704-710.

PMID- 16466493
TI  - Commentary on Pascoe SW and Neal RD (2004) Primary care: questionnaire survey of
      alternative forms of patient and nurse face-to-face consultations. Journal of
      Clinical Nursing 13, 406-407.

PMID- 16466494
TI  - Developing efficient search strategies to identify reports of adverse effects in
      MEDLINE and EMBASE.
AB  - OBJECTIVE: This study aimed to assess the performance, in terms of sensitivity
      and precision, of different approaches to searching MEDLINE and EMBASE to
      identify studies of adverse effects. METHODS: Five approaches to searching for
      adverse effects evidence were identified: approach 1, using specified adverse
      effects; approach 2, using subheadings/qualifiers; approach 3, using text words;
      approach 4, using indexing terms; approach 5, searching for specific study
      designs. The sensitivity and precision of these five approaches, and combinations
      of these approaches, were compared in a case study using a systematic review of
      the adverse effects of seven anti-epileptic drugs. RESULTS: The most sensitive
      search strategy in MEDLINE (97.0%) required a combination of terms for specified
      adverse effects, floating subheadings, and text words for 'adverse effects'. In
      EMBASE, a combination of terms for specified adverse effects and text words for
      'adverse effects' provided the most sensitive search strategy (98.6%). Both these
      search strategies yielded low precision (2.8%). CONCLUSIONS: A highly sensitive
      search in either database requires a combination of approaches, and has low
      precision. This suggests that better reporting and indexing of adverse effects is
      required and that an effective generic search filter may not yet be feasible.

PMID- 16466495
TI  - Publishing trends in Chinese medicine and related subjects documented in
      WorldCat.
AB  - BACKGROUND: Chinese medicine (CM) has been the subject of increasing interest in
      the past 30 years, both as a discipline and in the larger context of alternative
      medicine. It has steadily been accepted by and integrated into the medical and
      health-care fields in many countries. OBJECTIVE: This study aims to gain an
      overview of how CM has been interpreted and presented to the world outside China
      and to identify emerging trends. METHODS: This study is designed to analyse the
      publishing trends of CM and related subjects in all languages except Chinese,
      ranging from books and serials to audio-visual and electronic resources found in
      WorldCat, the world's largest bibliographic database produced by OnLine Computer
      Library Center (OCLC). RESULTS: The findings showed a flourishing growth of
      publications in CM and related subjects beginning in the 1970s with greater
      coverage on acupuncture. The materials in English language constitute the major
      portion of total output. CONCLUSION: We conclude that Chinese medicine has
      steadily gained recognition in the world based on the analysis of publication
      records. The translation of original works and analysis of journal literature and
      conference proceedings on Chinese medicine merit further study.

PMID- 16466497
TI  - A journal club is an effective tool for assisting librarians in the practice of
      evidence-based librarianship: a case study.
AB  - OBJECTIVE: To establish a journal club for librarians, which aimed to develop
      appraisal skills and assist in the application of research to practice. METHODS:
      Fourteen health librarians were invited to attend a journal club. Each month a
      librarian was responsible for preparing a scenario, choosing a research paper,
      and selecting a checklist. The paper was appraised by the club, and a critically
      appraised topic (CAT) prepared. Six months later, a questionnaire was sent to all
      librarians. RESULTS: Six out of 14 librarians attended the journal club and five
      out of six returned the questionnaire. All five agreed that attending the journal
      club helped them develop appraisal skills, write a CAT and be more critical of
      research. Four agreed they always identified a research paper first, then
      formulated a question. One librarian agreed that applying results to their own
      practice was difficult, one disagreed and three were neutral. CONCLUSION: Journal
      clubs can be effective at developing appraisal skills and writing a CAT, as well
      as increasing the reading of library research. Librarians still need assistance
      in identifying and using questions directly from their own practice. The journal
      club has helped some librarians to apply evidence to practice, but others find
      the research is not always directly relevant.

PMID- 16466496
TI  - Market orientation: a concept for health libraries.
AB  - OBJECTIVES: This paper is the result of exploratory research forming part of
      ongoing study into the value and relevance of market orientation as a strategic
      option for library managers. The aim of the study is to gain an understanding of
      the concept of market orientation relative to the health library sector.
      METHODOLOGY: A focus group was used to gather data from health librarians working
      at different levels in the sector. The data was coded and categorized by an
      expert panel and analysed using a taxonomic map developed during the study.
      RESULTS: Health library professionals define and understand market orientation in
      the same way as the concept is defined in the management literature. Their
      understanding of the concept is developing. A greater emphasis is given to some
      aspects of market orientation than others. CONCLUSIONS: There are implications
      for further research. Methods used to measure market orientation in other domains
      are likely to be relevant for libraries. Research should be extended to different
      sectors to explore any cross-sector differences. Fostering an organizational
      culture that supports market orientation has implications for service management
      and development.

PMID- 16466498
TI  - Clinical effectiveness and allied health professionals: an information needs
      assessment.
AB  - OBJECTIVE: To determine the information needs and support required by AHPs whilst
      building services based on clinical effectiveness. METHODS: A qualitative
      approach using action research in co-operation with a Rehabilitation Department
      Clinical Effectiveness group, leading to interviews with eight therapists. The
      sampling strategy was purposive. RESULTS: Therapists have well-developed
      professional networks, but are unsure how to access traditional library areas.
      Library training can stop AHPs in asking for help or services, whilst the library
      is thought to be very different to their everyday work, but confidence in using
      the library service can be acquired by getting to know a librarian. A
      departmental-based service was thought to provide better access to, and
      understanding of, information through mentorship, whilst also providing up-to
      date evidence so that clinicians can concentrate on their clinical work whilst
      being more clinically effective. CONCLUSIONS: When seeking information, AHPs are
      more likely to use professional networks than libraries. However, when working
      alongside an AHP, a librarian can upgrade information-seeking skills through
      mentorship, whilst named library contacts can make it easier to access the
      library for help.

PMID- 16466500
TI  - Information retrieval for online patient groups.

PMID- 16466501
TI  - Evaluating the impact of a project promoting library and information services to
      primary care in Nottingham, UK.

PMID- 16466499
TI  - Knowledge in the Palm of your hands: PDAs in the clinical setting.
AB  - OBJECTIVE: To explore the impact of hand-held computers on patient care by
      identifying: (i) how often clinical staff accessed resources on hand-held
      computers to inform their clinical decision making; (ii) Which hand-held
      resources were thought to be most useful in the clinical setting; (iii) the
      barriers to using hand-held resources to support patient care. DESIGN: A
      descriptive study comparing aspects of Personal Digital Assistant (PDA) resource
      use in two phases, between August 2002 and December 2003. There was variability
      in the way that resources were accessed between the two studies. SETTING:
      University Hospitals of Leicester NHS Trust, an acute teaching hospital, and one
      primary care practice. PARTICIPANTS: A purposive sample of 14 clinical and
      librarian staff participated in phase one and 14 in phase two of the study.
      Participants consisted of consultants, nurses, pharmacist, junior doctors,
      clinical librarians, and a general practitioner. MAIN OUTCOME MEASURES: Baseline
      Data Questionnaire to identify the participants' level of knowledge and use of
      hand-helds on entering the study. End-of-phase questionnaire with self-reported
      measures of use of the hand-held and PDA resources during the study. RESULTS: All
      of the participants used hand-helds in their clinical setting to support evidence
      based practice and education, but with varying frequency. More staff reported
      using the hand-held to answer specific patient questions in phase two than phase
      one of the study. UK resources were preferred to American resources. The 'plug-in
      and go' method using Secure Digital (SD) cards was preferred to downloading
      resources from the Internet. CONCLUSIONS: Hand-held technology is emerging as an
      effective clinical tool to aid evidence-based practice and support the
      educational needs of clinical staff. The hand-held can provide a critical mass of
      information that is relevant, quickly accessible and in a coherent format:
      delivering clinical information at the point of need with a resulting benefit to
      patient safety.

PMID- 16466502
TI  - Australian supermodel?--A practical example of evidence-based library and
      information practice (EBLIP).

PMID- 16466503
TI  - Learning and teaching.

PMID- 16466506
TI  - Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic
      classification. Part one.
AB  - Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely
      varying clinical behaviors, ranging from indolent to aggressive tumors with
      significant metastatic potential. However, the tendency for pathologists and
      clinicians alike is to refer to all squamoid neoplasms as generic SCC. No
      definitive, comprehensive clinicopathological system dividing cutaneous SCCs into
      categories based upon their aggressiveness has yet been promulgated. Therefore,
      we have proposed the following based upon the malignant potential of SCC
      variants, separating them into categories of low (< or = 2% metastatic rate),
      intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low
      risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC,
      tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation).
      Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal
      epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High
      risk subtypes include de novo SCC, SCC arising in association with predisposing
      factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease,
      adenosquamous carcinoma, and malignant proliferating pilar tumors. The
      indeterminate category includes signet ring cell SCC, follicular SCC, papillary
      SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear
      cell SCC. Subclassification of SCC into these risk-based categories, along with
      enumeration of other factors including tumor size, differentiation, depth of
      invasion, and perineural invasion will provide prognostically relevant
      information and facilitate the most optimal treatment for patients.

PMID- 16466508
TI  - Smooth muscle pattern is more reliable than the presence or absence of an
      internal elastic lamina in distinguishing an artery from a vein.
AB  - BACKGROUND: Major pathology textbooks suggest that the shape of the vessel and
      the presence or absence of an internal elastic lamina are the best means to
      distinguish an artery from a vein. Because the shape of the vessel is highly
      dependent upon the plane of section, the internal elastic lamina is often cited
      as a more reliable criterion. After evaluating a patient with superficial
      thrombophlebitis, in whom these conventional criteria had led to a misdiagnosis
      of polyarteritis nodosa, we sought to determine whether the pattern of smooth
      muscle in the media is a more sensitive discriminator between an artery and a
      vein. METHODS: Anatomically identified arteries and veins were harvested from
      extremity amputation specimens and stored autopsy organ specimens and reviewed by
      two dermatopathologists who were blinded to the gross pathologist's impression.
      The biopsies were assessed for the smooth muscle pattern and the presence or
      absence of an internal elastic lamina. RESULTS: Forty-seven of the 50 cases (94%)
      were concordant with the pathologist's gross impression using only the smooth
      muscle pattern to differentiate an artery from a vein. On the basis of the
      presence or absence of an internal elastic lamina, 41 of 50 cases (82%) were
      concordant with the prosector's designation of the vessel. LIMITATIONS: Vessels
      were harvested from a variety of sites, with lower extremity vessels
      predominating. There may be some regional variability not addressed in this
      study. CONCLUSION: In this study, the pattern of muscle fibers within the
      vascular media discriminated between arteries and veins better than assessment of
      the presence or absence of an internal elastic lamina. Although no single
      criterion is 100% reliable, assessment of both these criteria may minimize the
      risk of misinterpreting vessels in the deep dermis and subcutis.

PMID- 16466507
TI  - Expression profiles of melanogenesis-related genes and proteins in acquired
      melanocytic nevus.
AB  - We used three types of AMN to investigate the expression profiles of
      melanogenesis-related genes [tyrosinase, tyrosinase-related protein-1 (TRP1),
      dopachrome tautomerase (TRP2), Pmel-17/gp100, P-protein, and microphthalmia
      associated transcription factor (MITF)], as well as tyrosinase, TRP1, Pmel
      17/gp100, and MITF proteins. RESULTS: All melanogenesis-related genes examined in
      the junctional type were expressed in the basal epidermal layer. In the compound
      and intradermal types, mRNA for tyrosinase, TRP2, and MITF was expressed in all
      of the AMN cells. However, the expression of TRP1, P-protein, and Pmel-17/gp100
      in the compound type and TRP1 in the intradermal type became weaker in accordance
      with the depth of the dermis layer, as compared to those levels in the basal to
      upper dermis layer. Although tyrosinase and Pmel-17/gp100 mRNA in the compound
      and intradermal types was expressed in the intraepidermal and dermal components,
      immunohistochemical staining showed that tyrosinase proteins were not detected in
      the lower dermis layer and Pmel-17/gp100 proteins were not detected in the
      dermis. CONCLUSIONS: Our results suggest that all nevus cells that constitute AMN
      tissue originate from melanocytes. Further, there may be differences in the
      transcription levels of melanogenesis-related genes as well as in their post
      transcriptional regulation between nevus cells located in the basal epidermal to
      upper dermis layer and those in the lower dermis layer.

PMID- 16466509
TI  - Characterization of induced mucosal connective tissue separation--a comparison of
      six different techniques.
AB  - BACKGROUND: Artificial separation of oral mucosa into epithelium and connective
      tissue represents the first step in investigating both the basement membrane zone
      and its two components (epithelium and connective tissue) separately. It is a
      useful tool in analysing the possible role of hepatitis C virus in the
      pathogenesis of oral lichen planus (OLP). The aim of the present study was to
      test different methods to separate the epithelium from the connective tissue of
      oral mucosa affected by OLP as a preliminary step for further immunohistochemical
      or molecular investigations. PATIENTS AND METHODS: Fourteen tissue biopsies of
      the oral mucosa of clinically and histopathologically confirmed OLP lesions
      underwent epithelial connective separation (ECS) using six different reagents.
      RESULTS AND CONCLUSIONS: Among the separation methods tested, CaCl2 1 M at 37
      degrees C for 30 min, NaCl 1 M at 4 degrees C for 26 h and elastase at 4 degrees
      C for 22 h allowed good ECS without structural alteration or tissue loss. The
      present study provides useful information regarding techniques to separate the
      epithelium from the connective tissue as a preliminary step to investigate oral
      mucosa affected by OLP from an immunohistochemical or molecular viewpoint.

PMID- 16466510
TI  - CD44 and hyaluronate expression in follicular mucinosis.
AB  - BACKGROUND: CD44 is a membrane glycoprotein and the major cell-surface receptor
      of hyaluronate (HA). Lack of CD44 expression in mouse epidermis leads to an
      abnormal HA accumulation in the dermis, indicating an important role of CD44 in
      local HA metabolism. Decrease of epidermal CD44 expression in patients of lichen
      sclerosus et atrophicus is potentially responsible for dermal deposition of HA in
      this disease. Stromal HA accumulation is associated with decreased or lost
      expression of CD44 in perifollicular solitary cutaneous myxoma, myxoid
      dermatofibroma, and dermatofibrosarcoma protuberans. METHODS: We examined the
      expression of CD44 and HA in the skin biopsy specimens of 10 patients with
      follicular mucinosis by using CD44-specific antibodies and biotinylated HA
      binding protein (HABP), respectively. RESULTS: No difference of CD44 expression
      was observed in the follicular keratinocytes when compared with those of
      unaffected interfollicular epidermis. The follicular zones of mucin deposition
      were strongly positive for HA. A weak interkeratinocyte staining for HA was also
      observed in the interfollicular epidermis. However, HABP staining revealed a
      stronger reactivity in the follicular keratinocytes surrounding the mucin
      accumulated areas compared to the interfollicular keratinocytes. CONCLUSION: Our
      results suggest an active secretion of HA by follicular cells in follicular
      mucinosis.

PMID- 16466511
TI  - Perivascular myoma of myopericytoma and myofibromatosis-type arising in a chronic
      scar.
AB  - We describe a case of a cutaneous perivascular myoma with features overlapping
      between the myofibromatosis and the myopericytoma type. The patient is a 58-year
      old woman with a painless plaque-like and multinodular lesion in the pretibial
      dermis and subcutaneous tissue. She had repeated trauma to this site, first in
      her early youth that left an area of hyperpigmentation, and then again at age 40.
      The biopsy showed a biphasic pattern with a myofibromatosis-type component
      composed of spindle cell myoid nodules and more cellular round cell areas. The
      myopericytoma-like areas appeared to be infiltrating along vessels. These areas
      contained aggregates of immature-appearing cells arranged concentrically around
      vascular lumina in a manner reminiscent of pericytes. Immunohistochemical stains
      showed focal positivity for smooth muscle actin. Immunohistochemical and
      ultrastructural studies have showed these pericyte-like cells to be of a myoid
      origin. The reason for the neoplastic proliferation of perivascular myoid cells
      is presently unknown. The association of trauma and neoplastic transformation of
      the skin is rare. We report the first case of a cutaneous perivascular myoma
      arising in a chronic scar.

PMID- 16466512
TI  - Marginal zone lymphoma with a dual cutaneous and leukemic presentation and an
      aberrant myeloid-monocytic phenotype.
AB  - Marginal zone lymphoma (MZL) is an indolent neoplasm of mature B cells,
      classified by the World Health Organization into three categories: nodal,
      splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT lymphoma).
      We present an unusual case of MZL with cutaneous, leukemic, and bone marrow
      involvement at presentation and expression of an aberrant myeloid-monocytic
      phenotype. This case is best classified as MZL of leukemic subtype.

PMID- 16466513
TI  - Necrolytic migratory erythema.
AB  - BACKGROUND: Necrolytic migratory erythema is considered to be a paraneoplastic
      dermatosis. The classical symptoms are associated with alpha-cell pancreatic
      islet cell tumor or 'glucagonoma'. Generally, extracutaneous hallmarks of this
      disease include weight loss, diabetes, anaemia and diarrhoea. OBSERVATION: We
      report a case of a 39-year-old woman with a 3-year history of recalcitrant
      psoriasiform eruption, who had no other associated symptoms on routine
      examination. Histologic examinations suggested necrolytic migratory erythema.
      Abdominal computer tomography was performed, which revealed a tumor in the tail
      of the pancreas. After distal resection of the pancreas her skin symptoms
      resolved in a few days time. Histology was consistent with glucagonoma. She is
      clinically well and symptomless and no signs of metastasis after 4 years.
      CONCLUSIONS: It is infrequent to have only necrolytic migratory erythema,
      hyperglucagonaemia and islet-cell tumor but no other extracutaneous symptoms in
      glucagonoma syndrome. To our knowledge, ours is the second such case reported in
      the literature. Skin symptoms are important, often they are the clue to the
      diagnosis of glucagonoma syndrome.

PMID- 16466514
TI  - Squamous cell carcinoma of the skin: dual differentiations to rare basosquamous
      and spindle cell variants.
AB  - Basosquamous carcinoma (BSC) is defined as a tumor containing the areas of both
      basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a transition
      zone linking the two. Spindle cell squamous carcinoma (SCSC) may have a variable
      component of conventional SCC and spindle cells. We present a case of an 89-year
      old woman with an eruption on the scalp for several decades. Grossly, the lesion
      measured 8.5 x 6.0 x 1.8 cm and consisted of a gray-white and focally black
      tumor. Microscopically, a non-ulcerated upper part of the tumor consisted of
      large polygonal squamoid cells with occasional keratinization (SCC), trabecular
      growth of basaloid cells with peripheral palisading (BCC), and an area in which
      both the components were intermingled. The rest of the tumor was a myxoid area
      with elongated fusiform spindle cells, which appeared to arise from conventional
      SCC. Immunohistochemically, the tumor cells in the SCSC (both conventional and
      spindle cell) area co-expressed CAM5.2, and vimentin. Ber-EP4 was positive in the
      BCC area with the transition zone of SCC and BCC showing diminished staining.
      Epithelial membrane antigen was focally positive in the conventional SCC area. To
      our knowledge, this is the first case report of SCC of the skin that has dual
      differentiations to BSC and SCSC.

PMID- 16466515
TI  - Proliferative nodules with balloon-cell change in a large congenital melanocytic
      nevus.
AB  - The balloon-cell nevus was first described over 100 years ago. Since then,
      balloon-cell changes of melanocytes have been noted in numerous tumors, including
      melanoma, blue nevus, and Spitz nevus. Whether these changes reflect cellular
      deterioration or proliferative changes is a matter of debate. We report a case in
      which balloon-cell changes were found within proliferative nodules occurring in a
      large congenital melanocytic nevus.

PMID- 16466516
TI  - Subclinical chronic lymphocytic leukaemia associated with a 13q deletion
      presenting initially in the skin: apropos of a case.
AB  - INTRODUCTION: B-cell chronic lymphocytic leukaemia (B-CLL) represents a low-grade
      B-cell lymphoproliferative disease that is the most common leukaemia in adults.
      The neoplastic cell is an autoreactive CD5 CD23 B lymphocyte. B-CLL may involve
      the skin, typically in the context of known disease. We present a case of
      subclinical B-CLL presenting initially in the skin. CASE REPORT: A 73-year-old
      male developed a lesion on his right cheek in April 2003 compatible with basal
      cell carcinoma. The re-excision specimen contained a well-differentiated atypical
      lymphocytic infiltrate consistent with B-CLL along with residual carcinoma.
      Subsequent laboratory studies revealed peripheral blood lymphocytosis with smudge
      cells. A diagnosis was made of Rai stage 0 CLL. Chromosomal studies on peripheral
      blood showed a deletion at 13q14.3. Excision of a second primary skin carcinoma
      revealed a squamous cell carcinoma in association with B-CLL that was identical
      to his previously diagnosed skin involvement. CONCLUSION: This case identifies a
      cutaneous presentation of subclinical B-CLL. There are two prior reports
      describing B-CLL presenting initially in the skin. In one case, the infiltrates
      were incidental on a re-excision specimen. The second report suggests 16% of B
      CLL patients have cutaneous manifestations as the first sign of disease.

PMID- 16466517
TI  - Proceedings of the 3rd Copenhagen Workshop on Environment, Reproductive Health
      and Fertility, January 15-18, 2005. Copenhagen, Denmark.

PMID- 16466518
TI  - Is human fecundity declining?
AB  - Summary The decreasing trends in fertility rates in many industrialized countries
      are now so dramatic that they deserve much more scientific attention. Although
      social and behavioural factors undoubtedly play a major role for these trends, it
      seems premature, and not based on solid information, to conclude that these
      trends can be ascribed to social and behavioural changes alone. There is evidence
      to suspect that changing lifestyle and increasing environmental exposures, e.g.
      to endocrine disrupters, are behind the trends in occurrence of male reproductive
      health problems, including testis cancer, undescended testis and poor semen
      quality. These biological factors may also contribute to the extremely low
      fertility rates. However, the necessary research is complex and requires non
      traditional collaboration between demographers, epidemiologists, clinicians,
      biologists, wild life researchers, geneticists and molecular biologists. This
      research effort can hardly be carried out without major support from governments
      and granting agencies making it possible to fund collaborative projects within
      novel research networks of scientists.

PMID- 16466519
TI  - Register data on Assisted Reproductive Technology (ART) in Europe including a
      detailed description of ART in Denmark.
AB  - The European Society for Human Reproduction and Embryology (ESHRE) has monitored
      Assisted Reproduction in Europe since 1997. In 2001, 579 clinics from 23
      countries reported 289,690 treatment cycles with: in vitro fertilization (IVF)
      120,946, intracytoplasmatisk sperm injection (ICSI) 114,378, frozen embryo
      replacements (FER) 47,195 and egg donation (ED) 7,171. Intrauterine inseminations
      are less consistently reported, but in 2001, 15 countries reported 67,124 cycles
      (IUI-H 52 949 and IUI-D 14 185). Data from 2001 showed that in 12 countries,
      where all clinics reported the in vitro techniques to the register, 829 treatment
      cycles were performed per million inhabitants. The availability was highest in
      the Nordic countries (range 975-1,923 cycles). The proportion of infants born
      after ART with in vitro techniques ranged from 0.2% in Latvia to 3.9% in Denmark.
      In general, the impact of the in vitro techniques on the birth rate is highest in
      the Nordic countries (range 2.2-3.9%). Denmark is the only country with an
      established National ART reporting system involving all ART treatments both with
      the in vitro techniques and intrauterine inseminations. In the year 2002, a total
      of 20,837 treatment cycles were performed. The result was that 6.2% of all
      infants were born after assisted reproduction.

PMID- 16466520
TI  - Trends in European fertility: should Europe try to increase its fertility
      rate...or just manage the consequences?
AB  - Currently across Europe, birth rates are falling and the population is aging.
      This paper describes these trends and assesses which policies can prevent or
      mitigate the adverse consequences of these two trends.

PMID- 16466521
TI  - Fertility rates and future population trends: will Europe's birth rate recover or
      continue to decline?
AB  - Europe has long completed its demographic transition from high birth and death
      rates to low birth and death rates. But the demographic transition paradigm that
      has been very useful for explaining global demographic trends during the 20th
      century and that still has strong predictive power when it comes to projecting
      future trends in countries that still have high fertility, has nothing to say
      about the future of fertility in Europe. The currently popular notion of a
      'second demographic transition' is a useful way to describe a bundle of
      behavioural and normative changes that recently happened in Europe, but it has no
      predictive power. The social sciences have not yet come up with a useful theory
      to predict the future fertility level of post-demographic transition societies.
      We even do not know whether the trend will be up or down. Given the lack of a
      predictive theory, this paper will try to do two things: (i) Summarize different
      substantive arguments that would either suggest the assumption of a recovery of
      fertility rates in Europe or alternatively, imply further declines. (ii) Convert
      this discussion of the uncertainty of future fertility trends into probabilistic
      population projections for Europe, thus highlighting the implications of
      alternative fertility levels over the coming years. We will also discuss trade
      offs between fertility and immigration, and the phenomenon that Europe now has
      entered a period of negative momentum of population growth.

PMID- 16466523
TI  - Bio-social determinants of fertility.
AB  - This paper reviews several studies that investigated the potential role of
      genetic factors in determining fertility outcomes. Our review demonstrates
      convincingly that fertility contains genetic variance; that is, differences
      between humans in their genetic make-up affects their fertility outcomes and
      fertility-related behaviours. This finding is robust using both heritabilities
      and coefficients of genetic variation, and using both direct measures of
      fertility outcomes and also fertility precursors like fecundity, marriage,
      fertility expectations and attempts to get pregnant (proception). Moreover,
      genetic variance can change over short periods of time or across educational
      levels, specifically for females, and the relevance of genetic variance seems to
      increase during times of increasing reproductive choice.

PMID- 16466522
TI  - Fertility and abortion rates in the United States, 1960-2002.
AB  - This paper provides a general overview of trends in the United States (US) birth,
      fertility and abortion data from 1960 to 2002. Rates by age, race and Hispanic
      origin are also discussed. Data presented in this paper are derived primarily
      from published reports of the US government's Centers for Disease Control and
      Prevention's National Center for Health Statistics. In 2002, there were 4,021,726
      births in the US. The general fertility rate was 64.8 births per 1,000 women aged
      15-44 years, the total fertility rate was 2013.0 children per 1,000 women, and
      the net reproduction rate was 968 daughters per 1000 women. These rates have
      declined in the US since 1960, down by at least 44% for all rates. While these
      rates have been declining, there are substantial differences in fertility
      patterns by age and race and Hispanic origin. Rates for women, 30 years of age
      and over, increased between 1980 and 2002. In contrast, rates for women under 25
      years of age rose considerably during the late 1980s, and then decreased sharply
      since 1991. Rates for women in their late twenties (25-29 years of age), the
      principal childbearing ages, have fluctuated within a narrow range throughout
      this period (1980-2002). As a result of the increase in births to older women,
      the mean age of mother at first birth increased by nearly 4 years from 1968 to
      2002. In 2000, the latest year for which data are available, there were 21.3
      induced abortions per 1000 women aged 15-44 years, down from 27.4 in 1990. The
      total abortion rate, average number of legally induced abortions that would occur
      to a hypothetical cohort of 1000 women, was 672.0 abortions per 1,000 women in
      2000, down from 785.5 in 1980. The abortion rate has declined fairly steadily
      since 1980. Like the birth and fertility rates, substantial differences in
      abortion rates exist by age and race and Hispanic origin. The rates of induced
      abortion increased for women in their thirties between 1980 and 2000, whereas
      rates for women under 25 years of age and women 40 years of age and over
      decreased since 1980. The rate for women 25-29 years of age changed little. The
      rate of induced abortion was considerably higher for non-Hispanic black women
      (57.4) in 2000 than for non-Hispanic white women (11.7). The rate for Hispanic
      women (30.6) was intermediate. The total abortion rate was also much higher for
      non-Hispanic black women than non-Hispanic white and Hispanic women.

PMID- 16466524
TI  - Coordinated European investigations of semen quality: results from studies of
      Scandinavian young men is a matter of concern.
AB  - For many years it has been acknowledged that Danish and Norwegian men have one of
      the highest risks in the world for testicular cancer in sharp contrast to
      neighbouring Baltic men from Finland, Estonia and Lithuania. As an association
      between poor semen quality and testicular cancer has been established, it was
      suggested that men from high-risk testicular cancer areas would be more likely to
      have poor semen quality. However, previous studies were not able to elucidate
      this question due to their retrospective nature. In prospectively designed and
      strictly controlled studies of fertile men, the existence of regional differences
      in semen quality was confirmed. In addition, studies of men from the general
      populations were undertaken and a similar regional difference in semen quality
      was detected. Men from the eastern part of the Nordic-Baltic area had better
      semen quality than men from the western part. These findings parallel the
      incidence of testicular cancer in these regions. Approximately 20% of young men
      from Norway and Denmark had sperm concentrations below the World Health
      Organization reference level of 20 x 10(6) spermatozoa/mL, and approximately 40%
      had <40 x 10(6) spermatozoa/mL which, according to recent publications, may be
      the 'threshold' below which fecundity declines. In Denmark, the situation is of
      concern and a continued surveillance of semen quality in young men was
      established in 2001 by a government-supported programme.

PMID- 16466526
TI  - Sperm function tests and fertility.
AB  - Traditionally, the diagnosis of male infertility has depended upon a descriptive
      evaluation of human semen with emphasis on the number of spermatozoa that are
      present in the ejaculate, their motility and their morphology. The fundamental
      tenet underlying this approach is that male fertility can be defined by reference
      to a threshold concentration of motile, morphologically normal spermatozoa that
      must be exceeded in order to achieve conception. Many independent studies have
      demonstrated that this fundamental concept is flawed and, in reality, it is not
      so much the absolute number of spermatozoa that determines fertility, but their
      functional competence. In the light of this conclusion, a range of in vitro tests
      have been developed to monitor various aspects of sperm function including their
      potential for movement, cervical mucus penetration, capacitation, zona
      recognition, the acrosome reaction and sperm-oocyte fusion. Such functional
      assays have been found to predict the fertilizing capacity of human spermatozoa
      in vitro and in vivo with some accuracy. Recent developments in this field
      include the introduction of tests to assess the degree to which human spermatozoa
      have suffered oxidative stress as well as the integrity of their nuclear and
      mitochondrial DNA. Such assessments not only yield information on the fertilizing
      capacity of human spermatozoa but also their ability to support normal embryonic
      development.

PMID- 16466525
TI  - Semen quality in fertile US men in relation to geographical area and pesticide
      exposure.
AB  - We conducted the first US study to compare semen quality among study centres
      using standardized methods and strict quality control. We present data on semen
      quality in partners of 493 pregnant women recruited through prenatal clinics in
      four US cities during 1999-2001. Sperm concentration, semen volume and motility
      were determined at the centres and morphology was assessed at a central
      laboratory. While between-centre differences in sperm morphology and sample
      volume were small, sperm concentration and motility were significantly reduced in
      Columbia, MO (MO) relative to men in New York, NY, Minneapolis, MN and Los
      Angeles, CA; total number of motile sperm was 113 x 10(6) in MO and 162, 201 and
      196 x 10(6) in CA, MN and NY respectively. Differences among centres remained
      significant in multivariate models that controlled for abstinence time, semen
      analysis time, age, race, smoking, history of sexually transmitted disease and
      recent fever (all p-values <0.01). We hypothesized that poorer sperm
      concentration and motility in MO men relative to other centres might be related
      to agricultural pesticides that are commonly used in the mid-west. We
      investigated this hypothesis by conducting a nested case-control study within the
      MO cohort. We selected 25 men in this cohort for whom all semen parameters
      (concentration, % normal morphology and % motile) were low as cases and an equal
      number of men for whom all semen parameters were within normal limits as
      controls. We measured metabolites of eight non-persistent, current-use pesticides
      in urine samples the men had provided at the time of semen collection. Pesticide
      metabolite levels were elevated in cases compared with controls for the
      herbicides alachlor and atrazine, and for the insecticide diazinon (2-isopropoxy
      4-methyl-pyrimidinol) (p-values for Wilcoxon rank test = 0.0007, 0.012, and
      0.0004 for alachlor, atrazine and diazinon respectively). Men with higher levels
      of alachlor or diazinon were significantly more likely to be cases than men with
      low levels [odds ratios (OR) = 30.0, 16.7 for alachlor and diazinon
      respectively], as were men with atrazine over the limit of detection (OR = 11.3).
      These associations between current-use pesticides and reduced semen quality
      suggest that agricultural chemicals may have contributed to the reduced semen
      quality seen in fertile men from mid-Missouri.

PMID- 16466527
TI  - Mouse models for genes involved in impaired spermatogenesis.
AB  - Since the introduction of molecular biology and gene ablation technologies there
      have been substantial advances in our understanding of how sperm are made and
      fertilization occurs. There have been at least 150 different models of
      specifically altered gene function produced that have resulted in male
      infertility spanning virtually all aspects of the spermatogenic, sperm maturation
      and fertilization processes. While each has, or potentially will reveal, novel
      aspects of these processes, there is still much of which we have little
      knowledge. The current review is by no means a comprehensive list of these mouse
      models, rather it gives an overview of the potential for such models which up to
      this point have generally been 'knockouts'; it presents alternative strategies
      for the production of new models and emphasizes the importance of thorough
      phenotypic analysis in order to extract a maximum amount of information from each
      model.

PMID- 16466529
TI  - Adverse effects of environmental antiandrogens and androgens on reproductive
      development in mammals.
AB  - Within the last decade, several classes of chemicals have been shown in
      laboratory studies to disrupt reproductive development by acting as androgen
      receptor (AR) antagonists and/or inhibitors of fetal Leydig cell testosterone
      production. Some phthalate esters alter gubernacular differentiation by reducing
      insulin-like 3 (insl3) mRNA levels. We have found that AR antagonists and
      inhibitors of fetal testis hormone production generally induce cumulative,
      apparently dose-additive adverse effects when administered in mixtures. New
      research has also revealed the presence of androgens in the environment.
      Effluents from pulp and paper mills display androgenic activity of sufficient
      potency to masculinize and/or sex-reverse female fish. Effluent from beef cattle
      concentrated animal feedlot operations from the United States also displays
      androgenic activity in vitro, due, in part, to the presence of a steroid used to
      promote growth in beef cattle. In summary, we are only beginning to identify the
      classes of chemicals that have the potential to alter the androgen signalling
      pathway in utero. This review will (i) present information on the classes of
      environmental chemicals that display antiandrogenic and androgenic activities in
      vitro and in vivo, and (ii) provide an insight into how exposure to mixtures
      these chemicals might behave in utero.

PMID- 16466528
TI  - The foetal Leydig cell-- differentiation, function and regulation.
AB  - The foetal Leydig cell population arises shortly after testicular differentiation
      at around 12.5 dpc in the mouse and 6 weeks in the human. These cells function,
      primarily, to produce androgens which are essential for masculinization of the
      foetus. The origin of the foetal Leydig cells remains uncertain but it has been
      suggested that adrenocortical cells and foetal Leydig cells may share a common
      origin in an adreno-genital primordium. Studies in the mouse are beginning to
      identify factors such as desert hedgehog and platelet-derived growth factor which
      are required for foetal Leydig cell development. Regulation of foetal Leydig cell
      function remains uncertain in most species. Unlike the adult population of Leydig
      cells, the foetal Leydig cells in the mouse do not require luteinizing hormone
      (LH) to stimulate androgen production. An intact pituitary does appear to be
      required, however, and adrenocorticotrophic hormone (ACTH) will stimulate foetal
      Leydig cell function directly suggesting that both LH and ACTH act to maintain
      Leydig cell function in vivo. In the human LH/hCG is required for foetal Leydig
      cell function although the cells may also be sensitive to ACTH.

PMID- 16466531
TI  - Reproductive dysgenesis in wildlife: a comparative view.
AB  - Abnormal reproductive development in males has been linked to environmental
      contaminant exposure in a wide variety of vertebrates. These include humans,
      rodent models, and a large number of comparative wildlife species. In human
      males, abnormal reproductive development can manifest as a suite of symptoms,
      described collectively as testicular dysgenesis syndrome (TDS). TDS is also
      described as demasculinization or feminization of the male phenotype. The suite
      includes cryptorchidism, in situ germ cell carcinoma of the testis and overt
      testicular cancer, reduced semen quality, and hypospadias. In this paper, we
      review examples of TDS among comparative species. Wildlife exposed to
      environmental contaminants are susceptible to some of the same developmental
      abnormalities and subsequent symptoms as those seen in human males with TDS.
      There are additional end points, which are also discussed. In some cases, the
      symptoms are more severe than those normally seen in humans with TDS (i.e.
      oocytes developing within the testis) because some non-mammalian species exhibit
      greater innate reproductive plasticity, and are thus more easily feminized. Based
      on our review, we present an approach regarding the ontogeny of TDS. Namely, we
      suggest that male susceptibility to the androgynizing influences of environmental
      contaminants originates in the sexually undifferentiated embryo, which, in almost
      all species, including humans, consists of bipotential reproductive tissues.
      These tissues can develop as either male or female and their ultimate direction
      depends on the environment in which they develop.

PMID- 16466532
TI  - Effects of the plant growth regulator, chlormequat, on mammalian fertility.
AB  - This paper summarizes the consequences of exposure to chlormequat, a plant growth
      regulator, on reproduction in mammals. Plant growth regulators are chemicals used
      to manipulate plant growth, flowering and fruit yield. In grain crops, plant
      growth regulators are applied to promote sturdier growth and reduce the risk of
      lodging. Chlormequat is the most common plant growth regulator. Maximum residue
      limits of chlormequat in food products are 10 mg/kg in oat and pear, 3 mg/kg in
      wheat and rye, and 0.5 mg/kg in milk. In Denmark, results from experiments with
      pigs in the late 1980s showed sows that display impaired reproduction, mainly
      impaired oestrus, when fed grain from crop treated with chlormequat.
      Subsequently, the advisory body to the Danish pig industry recommended limiting
      the use of grain (maximum 30% of diet energy) from crop treated with chlormequat
      given to breeding stock due to the risk of reproduction problems. More recently,
      experiments have been conducted to evaluate the influence of chlormequat-treated
      wheat crop on reproductive function in male and female mice. These experiments
      showed that epididymal spermatozoa from mice on feed or water containing
      chlormequat had compromised fertilizing competence in vitro, while reproduction
      in female mice was not compromised. The estimated intake of chlormequat in the
      pig (0.0023 mg/kg bw/day) and the mouse (0.024 mg/kg bw/day) experiments was
      below the acceptable daily intake of 0.05 mg/kg bw/day. Reports from the industry
      do not show any effects at these low levels.

PMID- 16466533
TI  - Human exposure to phthalates via consumer products.
AB  - Phthalate exposures in the general population and in subpopulations are
      ubiquitous and widely variable. Many consumer products contain specific members
      of this family of chemicals, including building materials, household furnishings,
      clothing, cosmetics, pharmaceuticals, nutritional supplements, medical devices,
      dentures, children's toys, glow sticks, modelling clay, food packaging,
      automobiles, lubricants, waxes, cleaning materials and insecticides. Consumer
      products containing phthalates can result in human exposures through direct
      contact and use, indirectly through leaching into other products, or general
      environmental contamination. Historically, the diet has been considered the major
      source of phthalate exposure in the general population, but all sources,
      pathways, and their relative contributions to human exposures are not well
      understood. Medical devices containing di-(2-ethylhexyl) phthalate are a source
      of significant exposure in a susceptible subpopulation of individuals. Cosmetics,
      personal care products, pharmaceuticals, nutritional supplements, herbal remedies
      and insecticides, may result in significant but poorly quantified human exposures
      to dibutyl phthalate, diethyl phthalate, or dimethyl phthalate. Oven baking of
      polymer clays may cause short-term, high-level inhalation exposures to higher
      molecular weight phthalates.

PMID- 16466535
TI  - Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure-- an
      update and latest results.
AB  - Di(2-ethylhexyl)phthalate (DEHP) is a reproductive and developmental toxicant in
      animals and a suspected endocrine modulator in humans. There is widespread
      exposure to DEHP in the general population. Patients can be additionally exposed
      through DEHP-containing medical devices. Toxicokinetic and metabolic knowledge on
      DEHP in humans is vital not only for the toxicological evaluation of DEHP but
      also for exposure assessments based on human biomonitoring data. Secondary
      oxidized DEHP metabolites like mono-(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP),
      mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP), mono-(2-ethyl-5
      carboxypentyl)phthalate (5cx-MEPP) and mono-[2-(carboxymethyl)hexyl]phthalate
      (2cx-MMHP) are most valuable biomarkers of DEHP exposure. They represent the
      major share of DEHP metabolites excreted in urine (about 70% for these four
      oxidized metabolites vs. about 6% for MEHP); they are immune to external
      contamination and possibly the ultimate developmental toxicants. Long half-times
      of elimination make 5cx-MEPP and 2cx-MMHP excellent parameters to measure the
      time-weighted body burden to DEHP. 5OH-MEHP and 5oxo-MEHP more reflect the short
      term exposure. We calculated the daily DEHP intake for the general population (n
      = 85) and for children (n = 254). Children were significantly higher exposed to
      DEHP than adults. Exposures at the 95th percentile (21 and 25 microg/kg/day,
      respectively) scooped out limit values like the Reference Dose (RfD, 20
      microg/kg/day) and the Tolerable Daily Intake (TDI, 20-48 microg/kg/day) to a
      considerable degree. Up to 20-fold oversteppings for some children give cause for
      concern. We also detected significant DEHP exposures for voluntary platelet
      donors (n = 12, 38 microg/kg/apheresis, dual-needle technique). Premature
      neonates (n = 45) were exposed to DEHP up to 100 times above the limit values
      depending on the intensity of medical care (median: 42 microg/kg/day; 95th
      percentile: 1,780 microg/kg/day).

PMID- 16466534
TI  - Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl)
      phthalate.
AB  - Foetal exposure of male rats to di(n-butyl) phthalate (DBP) induces testicular
      changes similar to testicular dysgenesis syndrome in humans, including the
      formation of focal 'dysgenetic areas' within post-natal testes, surrounded by
      otherwise normal tubules exhibiting complete spermatogenesis. We hypothesize that
      these dysgenetic areas form when Sertoli (and other) cells are 'trapped' during
      the abnormal formation of large Leydig cell (LC) clusters in foetal life and by
      post-natal day (d) 4 these groups of intermingled cells attempt to form
      seminiferous tubules. It is likely that the malformed tubules resulting
      correspond to the dysgenetic areas evident in later life. This also provides a
      plausible explanation for the occurrence of LCs within seminiferous cords/tubules
      in or bordering the dysgenetic areas. In our previous studies intratubular LCs
      (ITLCs) were identified by immunostaining for 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD), the definitive LC cytoplasmic marker. However, the possibility
      remained that the 'presumptive' ITLCs were in fact Sertoli cells that had
      aberrantly gained the ability to express 3beta-HSD. Therefore, the aim of the
      present study was to fully characterize the ITLCs induced by in utero DBP
      exposure in d25 rats using a number of LC- (3beta-HSD, P450 side-chain cleavage
      enzyme, insulin-like factor 3, oestrogen receptor alpha) and Sertoli cell-
      (vimentin, Wilm's tumour-1) specific markers. Our results show that ITLCs express
      all four LC-specific markers but do not express either of the Sertoli cell
      markers. It is therefore concluded that the ITLCs are bona fide LCs that are
      abnormally located within the seminiferous tubules of DBP-exposed rats in post
      natal life.

PMID- 16466536
TI  - Human exposure assessment to environmental chemicals using biomonitoring.
AB  - In modern societies, humans may be exposed to a wide spectrum of environmental
      chemicals. Although the health significance of this exposure for many chemicals
      is unknown, studies to investigate the prevalence of exposure are warranted
      because of the chemicals' potential harmful health effects, as often indicated in
      animal studies. Three tools have been used to assess exposure: exposure
      history/questionnaire information, environmental monitoring, and biomonitoring
      (i.e. measuring concentrations of the chemicals, their metabolites, or their
      adducts in human specimens). We present an overview on the use of biomonitoring
      in exposure assessment using phthalates, bisphenol A and other environmental
      phenols, and perfluorinated chemicals as examples. We discuss some factors
      relevant for interpreting and understanding biomonitoring data, including
      selection of both biomarkers of exposure and human matrices, and toxicokinetic
      information. The use of biomonitoring in human risk assessment is not discussed.

PMID- 16466537
TI  - Possible impact of phthalates on infant reproductive health.
AB  - Phthalates adversely affect the male reproductive system in animals, inducing
      hypospadias, cryptorchidism, reduced testosterone production and decreased sperm
      counts. Phthalate effects are much more severe after in utero than adult
      exposure. Little is known about human health effects. This study discusses two
      recent studies on perinatal phthalate exposure, which indicated that human
      testicular development might be susceptible to phthalates. One study analysed
      phthalate monoesters in breast milk and reproductive hormone levels in infants.
      Five of six phthalates [monoethyl-(MEP), monobutyl- (MBP), monomethyl- (MMP),
      mono-2-ethylhexyl- (MEHP) and mono-isononyl phthalate (MiNP)] showed correlation
      with hormone levels in healthy boys, which were indicative of lower androgen
      activity and reduced Leydig cell function. MEP and MBP were positively correlated
      with serum sex hormone-binding globulin (SHBG) levels. MMP, MEP, MBP, MEHP and
      MiNP were positively correlated with the LH/testosterone ratio. Another study
      found a reduction of the anogenital index (AGI) in infant boys with increasing
      levels of MBP, MEP, monobenzyl- and mono-isobutyl phthalate in maternal urine
      samples during late-pregnancy. Boys with small AGI showed a high prevalence of
      cryptorchidism and small genital size. Taken together these studies suggest an
      antivirilizing effect of phthalates in infants. Most of these findings are in
      line with animal observations. However, the possible effects of MEP appear to be
      limited to humans. This may be due to differences in exposure routes (inhalation
      and dermal absorption which circumvents liver detoxification in addition to oral)
      and metabolism, or this association could be spurious. As phthalates are produced
      as bulk chemicals worldwide, these new findings raise concern about the safety of
      phthalate exposure for pregnant women and infants.

PMID- 16466539
TI  - Prochloraz: an imidazole fungicide with multiple mechanisms of action.
AB  - Prochloraz is an imidazole fungicide that is widely used in Europe, Australia,
      Asia and South America within gardening and agriculture. Screening studies have
      shown that prochloraz elicits multiple mechanisms of action in vitro, as it
      antagonizes the androgen and the oestrogen receptor, agonizes the Ah receptor and
      inhibits aromatase activity. In vivo prochloraz acts as an antiandrogen in the
      Hershberger assay by reducing weights of reproductive organs, affecting androgen
      regulated gene expressions in the prostate and increasing luteinizing hormone
      levels. In order to investigate the developmental effects of prochloraz, pregnant
      Wistar dams were dosed perinatally with 30 mg/kg prochloraz. Results showed that
      prochloraz significantly reduced plasma and testicular testosterone levels in
      gestational day 21 male foetuses, whereas testicular progesterone was increased.
      Gestational length was increased by prochloraz. In male pups a significant
      increase in nipple retention was found, and the weight of the bulbourethral
      glands was decreased. Behavioural studies showed that the activity level and
      sweet preference of adult males were significantly increased, indicating that
      exposure during gestation and lactation causes permanent effects in adulthood.
      Overall, these results indicate that prochloraz feminizes the male offspring
      after perinatal exposure, and that these effects are due, at least in part, to
      diminished fetal steroidogenesis. Thus, a novel endocrine disruptor has been
      identified that is mechanistically interesting as it elicits dual mechanisms of
      action and acts as an antiandrogen both by blocking the androgen receptor and by
      inhibiting fetal steroidogenesis. That a fungicide with such effects is so widely
      used is a cause for concern, and its use should be reduced, thereby minimizing
      the risk of human exposure.

PMID- 16466540
TI  - Breast cancer, oestrogens and environmental pollutants: a re-evaluation from a
      mixture perspective.
AB  - The continuing rise in breast cancer incidence rates in almost all Western
      countries cannot be explained entirely in terms of known risk factors of the
      disease process. Additional determinants need to be examined, among them exposure
      to environmental pollutants. With the demonstration that elevated levels of
      endogenous sex hormones and the use of hormones for the relief of menopausal
      symptoms are associated with the disease, the oestrogen hypothesis of breast
      cancer has received further empirical support. This has led to heightened
      concerns about the possible involvement of oestrogen-like pollutants, such as
      p,p'-Dichlorodiphenyldichloroethane (DDE). Case-control studies assessing whether
      women with breast cancer have elevated burdens of p,p'-DDE have produced results
      not suggestive of a link with cancer risks. However, possible effects of p,p'-DDE
      and other pollutants cannot be seen in isolation from sex hormones also present
      in serum. In view of the low potency of p,p'-DDE, and its low levels in serum, it
      seems unlikely that the chemical on its own will add significantly to the action
      of sex hormones. However, chemical analyses show that numerous pollutants with
      oestrogen-like effect profiles can be found in human tissues. Thus, the oestrogen
      hypothesis of breast cancer should be extended to encompass the multitude of
      these agents. Viewed from such a perspective, a putative role of organochlorines
      and other agents in breast cancer should not be dismissed prematurely. Instead,
      breast cancer epidemiology should face the reality of combined exposures and
      should take account of recent evidence from in vitro models demonstrating that a
      large number of oestrogen-like pollutants, all present at low levels, can act
      together to add to the internal oestrogenic load.

PMID- 16466541
TI  - Familial risks in testicular cancer as aetiological clues.
AB  - We used the nationwide Swedish Family-Cancer Database to analyse the risk for
      testicular cancer in offspring through parental and sibling probands. Among 0 to
      70-year-old offspring, 4,586 patients had testicular cancer. Standardized
      incidence ratios for familial risk were 3.8-fold when a father and 7.6-fold when
      a brother had testicular cancer. Testicular cancer was associated with leukaemia,
      distal colon and kidney cancer, melanoma, connective tissue tumours and lung
      cancer in families. Non-seminoma was associated with maternal lung cancer but the
      risk was highest for the late-onset cases, providing no support to the theory of
      the in utero effect of maternal smoking on the son's risk of testicular cancer.
      However, the theory cannot be excluded but should be taken up for study when
      further data are available on maternal smoking. The high familial risk may be the
      product of shared childhood environment and heritable causes.

PMID- 16466543
TI  - Dysfunction of the mitotic:meiotic switch as a potential cause of neoplastic
      conversion of primordial germ cells.
AB  - Germ cell tumours (GCT) are thought to arise as the result of a defect in early
      development, probably shortly after arrival of the migrating primordial germ
      cells (PGC) in the genital ridge when, if in a male genital ridge, the germ cells
      arrest in mitosis, but in a female genital ridge they enter meiosis. We suggest
      that dysfunction of the mitotic:meiotic switch, with cells aberrantly co
      expressing functions pertinent to both states, might provide the genetic
      instability that could initiate tumour development. If this hypothesis is
      correct, GCT could arise because of disruption in the function of any one of a
      number of different genes involved in controlling mitosis and meiosis, rather
      than being dependent upon a single prominent susceptibility gene. The Notch
      signalling system is one candidate system for controlling the switch and we have
      identified expression of Notch2 and Notch4 in seminomas and carcinoma in situ.
      Thus those two members of the Notch family are candidates for proto-oncogenes
      that could play a role in GCT development. We have also identified a human
      homologue of the synaptonemal complex protein, SCP3, and have found its
      apparently aberrant expression in some established EC cell lines. One possibility
      is that abnormal regulation of such proteins involved in the synaptonemal complex
      could also lead to genetic instability in PGC and so also initiate tumour
      development.

PMID- 16466542
TI  - From embryonic stem cells to testicular germ cell cancer-- should we be
      concerned?
AB  - Since the discovery of testicular carcinoma in situ (CIS) -- the precursor cell
      for the vast majority of germ cell tumours -- it has been proposed that CIS cells
      could be derived from transformed primordial germ cells or gonocytes. Here, we
      review recent discoveries not only substantiating that initial hypothesis but
      also indicating that CIS cells have a striking phenotypic similarity to embryonic
      stem cells (ESC). Many cancers have been proposed to originate from tissue
      specific stem cells [so-called 'cancer stem cells' (CSC)] and we argue that CIS
      may be a very good example of a CSC, but with exceptional features due to the
      retention of embryonic pluripotency. In addition, considering the fact that pre
      invasive CIS cells are transformed from early fetal cells, possibly due to
      environmentally induced alterations of the niche, we discuss potential risks
      linked to the uncontrolled therapeutic use of ESC.

PMID- 16466544
TI  - Germ cell atypia in undescended testes hinges on the aetiology of cryptorchidism
      but not the abdominal location per se.
AB  - Testicular carcinoma in situ (CIS), which precedes germ cell tumours, has been
      associated with coexistence or a history of testicular maldescent in 20-30% of
      human cases. The objective of this study was to determine if the abdominal
      location of the testis by itself affects differentiation of germ cells and why
      only some undescended testes manifest atypical germ cells. Groups (n = 4-6) of
      pregnant Dutch-Belted rabbits were treated on alternate days between gestation
      days 15 and 30 with anti-androgenic chemicals -- p,p' 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene (DDE; 100 mg/kg bw; oral), or flutamide (50 mg/kg; s.c.);
      oestrogenic chemical octylphenol (150 mg/kg; oral); or nothing. Groups (n = 4) of
      neonatal male pups from untreated litters were either implanted with oestradiol
      (0.5 mg; 60-day release), surgically rendered cryptorchid before testes
      transcended inguinal canal, or left untreated. Of the pups exposed in utero, four
      of the 12 DDE, two of the nine flutamide and one of the four octylphenol pups
      were unilaterally cryptorchid. All animals treated with oestradiol were
      bilaterally cryptorchid. Light and electron microscopic evaluation at 24-26 weeks
      revealed presence of atypical germ cells in the undescended testes of DDE-,
      octylphenol-, and oestradiol-exposed animals but not in flutamide-treated or
      surgical cryptorchids. These atypical cells exhibited morphological hallmarks of
      CIS, which included large nuclei with irregular contours, meandering nucleoli,
      swollen mitochondria, unusual cytoplasmic inclusions and occasional mitotic
      figures. As transformation of germ cells to CIS-like cells did not occur in
      flutamide or surgical groups, this phenomenon seems to be directly associated
      with the type of the chemical assault but not with the abdominal location of the
      testis per se.

PMID- 16466545
TI  - Recent data on pubertal milestones in United States children: the secular trend
      toward earlier development.
AB  - Tracking secular trends in the pubertal development of a country's children is
      important for social and public health reasons. Although comparable studies are
      largely lacking for US children over the last half century, existing data on
      girls, particularly that for menarche, indicate that the trend for earlier sexual
      maturatin has continued and that racial differences are significant, with African
      American girls developing earlier than white girls. Data on boys, though less
      reliable, suggest that they may be beginning maturation earlier as well. More
      studies on boys with reliable methodologies are needed. Earlier development may
      not be healthy and may indicate environmental problems that need to be further
      researched and addressed.

PMID- 16466546
TI  - Pubertal development in Danish children: comparison of recent European and US
      data.
AB  - Two recent epidemiological studies (PROS and NHANES III) from the USA noted
      earlier sexual maturation in girls, leading to increased attention
      internationally to the age at onset of puberty. We studied the timing of puberty
      in a large cohort of healthy Danish children in order to evaluate differences
      between USA and Denmark, as well as to look for possible secular trends in
      pubertal development. Healthy Caucasian children from public schools in Denmark
      participated in the study which was carried out in 1991-1993. A total number of
      826 boys and 1,100 girls (aged 6.0-19.9 years) were included, and pubertal stages
      were assessed by clinical examination according to methods of Tanner. In boys
      testicular volume was determined using an orchidometer. We found that age at
      breast development 2 (B2) was 10.88 years, and mean menarcheal age was 13.42
      years. Girls with body mass index (BMI) above the median had significantly
      earlier puberty (age at B2 10.42 years) compared with girls with BMI below the
      median (age at B2 11.24 years, p < 0.0001). Similarly, menarcheal age was
      significantly lower in girls with BMI above the median compared with girls with
      BMI below the median (13.12 vs. 13.70 years, p = 0.0012). In Danish boys we found
      that age at genital stage 2 (G2) was 11.83 years. Both sexes were significantly
      taller compared with data from 1964, but timing of pubertal maturation seemed
      unaltered. Finally, puberty occurred much later in Denmark compared with recent
      data from USA. We could not detect any downwards secular trend in the timing of
      puberty in Denmark between 1964 and 1991-1993 as seen in the US. Obesity
      certainly plays a role in the timing of puberty, but the marked differences
      between Denmark and USA cannot be attributed exclusively to differences in BMI. A
      possible role of other factors like genetic polymorphisms, nutrition, physical
      activity or endocrine disrupting chemicals must therefore also be considered.
      Therefore, we believe it is crucial to monitor the pubertal development closely
      in Denmark in the coming decades.

PMID- 16466547
TI  - Neuroendocrine mechanisms controlling female puberty: new approaches, new
      concepts.
AB  - Sexual development and mature reproductive function are controlled by a handful
      of neurones that, located in the basal forebrain, produce the decapeptide
      luteinizing hormone releasing hormone (LHRH). LHRH is released into the portal
      system that connects the hypothalamus to the pituitary gland and act on the
      latter to stimulate the synthesis and release of gonadotrophin hormones. The
      pubertal activation of LHRH release requires coordinated changes in excitatory
      and inhibitory inputs to LHRH-secreting neurones. These inputs are provided by
      both transsynaptic and glia-to-neurone communication pathways. Using cellular and
      molecular approaches, in combination with transgenic animal models and high
      throughput procedures for gene discovery, we are gaining new insight into the
      basic mechanisms underlying this dual control of LHRH secretion and, hence, the
      initiation of mammalian puberty. Our results suggest that the initiation of
      puberty requires reciprocal neurone-glia communication involving excitatory amino
      acids and growth factors, and the coordinated actions of a group of
      transcriptional regulators that appear to represent a higher level of control
      governing the pubertal process.

PMID- 16466548
TI  - Endocrine disrupters and human puberty.
AB  - In this overview of the literature, epidemiological research studying the effect
      of endocrine disrupters on the onset of puberty is summarized. In girls, earlier
      age at menarche was reported after exposure to polychlorinated biphenyls (PCBs),
      polybrominated biphenyls (PBBs), persistent pesticides
      [dichlorodiphenyltrichloroethane (DDT)] and phthalate esters. However, several
      other studies found no effect of these compounds on age at menarche or pubertal
      Tanner stages. One study reported a delaying effect of dioxin-like compounds on
      breast development. In boys, exposure to PCBs, PCDFs or the pesticide endosulfan
      was associated with delayed puberty or decreased penile length. Much of the
      results found in population studies are in accordance with experimental studies
      in animals. However, the mixture of different components with antagonistic
      effects (oestrogenic, anti-oestrogenic, anti-androgenic) and the limited
      knowledge about the most critical window for exposure (prenatal, peri-natal and
      pubertal) may hamper the interpretation of results.

PMID- 16466550
TI  - Ethnic differences in occurrence of TDS-- genetics and/or environment?
AB  - It has been hypothesized that poor semen quality, testis cancer, undescended
      testis and hypospadias are symptoms of one underlying entity, the so-called
      testicular dysgenesis syndrome (TDS). TDS was suggested to be a result of
      disruption of embryonal programming and gonadal development during foetal life
      and as aetiological factor, an impact of adverse environmental factors such as
      hormone disrupters, probably acting upon a susceptible genetic background, was
      suggested. Extensive studies considering the risk of TDS-related diseases in
      Denmark compared with Finland, showed higher sperm counts and lower risk of
      cryptorchidism and testicular cancer among Finns. However, when comparing these
      two populations, the question arises, to which degree this difference might be
      due to discrepancy in genetic background. A more obvious example of the impact of
      genetic factors on the risk of TDS concerns Afro-Americans having significantly
      lower incidence of testicular cancer when compared with Caucasians living in the
      USA. A yet unexplored scenario is a possible interaction between genetic and
      environmental/lifestyle-related factors, certain genotypes making individuals
      more susceptible to adverse exogenous exposures. Studying such interactions has
      biological, epidemiological and public health-related implications. It will help
      us to understand the background for the defects in male reproductive organs,
      facilitate proper design of epidemiological studies and add to identifying
      individuals susceptible to certain environmental and lifestyle-related hazards.
      Such 'susceptibility genes' need to be identified, those involved in the
      synthesis, action and metabolism of sex steroids being strong candidates.

PMID- 16466551
TI  - Y chromosome variants and male reproductive function.
AB  - The detailed analysis of the Y chromosome in men with azoospermia or severe
      oligozoospermia has resulted in the identification of three regions of the long
      arm of the human Y chromosome, termed AZFa, AZFb and AZFc, (AZF: AZoospermia
      Factor) that are currently deleted in men with otherwise unexplained
      spermatogenic failure. Screening for these deletions is now common in many
      infertility centres and in some instances they have a prognostic relevance.
      Recently, attention has turned to partial deletions of the AZFc region. At first
      sight some of these deletions appear to have little effect on fertility, whilst
      others appear to be associated with significant risk for developing spermatogenic
      failure. However, the relationship between these partial AZFc deletions, reduced
      sperm counts and infertility is the subject of a continuing intense debate. There
      is a pressing need to clarify the impact of partial AZFc deletions on human
      spermatogenesis. This requires large-scale studies on well-characterized
      normospermic and oligo/azoospermic individuals of different ethnic origins with
      multiple informative AZFc markers if the correlation between these deletions and
      the phenotype is finally to be resolved. The definition of Y chromosome variants
      (haplotypes) in cases of partial AZFc deletions is likely to play an essential
      role in understanding the contribution of the deletion to reduced sperm counts.

PMID- 16466553
TI  - Can the results of anorectal (abdominoperineal) resection be improved: are
      circumferential resection margins too often positive?
AB  - Carefully executed surgery for rectal cancer has reduced the incidence of local
      recurrence after restorative resection. Three recent large prospective series
      have confirmed the perception of a higher positive circumferential resection
      margin (CRM) rate after abdominoperineal resection. Tumour spread is different
      for low tumours and the surgical technique of abdominoperineal resection, perhaps
      better known as anorectal excision, may vary between surgeons. There is a need to
      redefine the place of anorectal excision and the contribution that can be made by
      pre-operative chemoradiation and/or extended surgery to reduce local recurrence
      and increase survival. Defined surgery, validated by histopathological
      assessment, as applied to TME surgery, would determine whether the perceived
      higher rates are due to the differences in routes of tumour spread or to
      surgically related variables. Unnecessary R1 or R2 resections and operative
      perforation can be minimized by an understanding of the surgical anatomy, the
      pattern of spread and difference in operative technique between anorectal
      excision and a low restorative operation. Surgical technique to maximize R0
      resection should be based on a detailed understanding of the pelvic fascia and
      the levator ani and the use of pre-operative imaging to define lines of excision.
      With the adoption of even lower restorative resection (intersphincteric) there is
      a need to reassess the method of anorectal excision. This may be achieved by
      histopathological assessment of CRM positivity and MDT audit to improve results.
      Clinical trials are essential.

PMID- 16466554
TI  - Impact of elective resection on plasma TIMP-1 levels in patients with colon
      cancer.
AB  - OBJECTIVE: Pre- and post-operative plasma tissue inhibitor of metalloproteinases
      1 (TIMP-1) levels have a prognostic impact on patients with colorectal cancer.
      However, the surgical trauma may play an essential role in regulation of plasma
      TIMP-1 levels, which in turn may influence subsequent TIMP-1 measurements.
      PATIENTS AND METHODS: Consecutively, 48 patients with colon cancer (CC) and 12
      patients with nonmalignant colonic disease were randomised to undergo elective
      laparoscopically assisted or open resection followed by fast track recovery.
      Plasma samples were collected just before and 1, 2 and 6 h after skin incision,
      and 1, 2, 8 and 30 days after surgery. TIMP-1 was determined concurrently in all
      samples by a validated ELISA method. RESULTS: Geometric mean preoperative TIMP-1
      level was 142 ng/ml (range 54-559 ng/ml) among CC patients compared with 106
      ng/ml (range 64-167 ng/ml) among patients with nonmalignant diseases (P<0.0001).
      TIMP-1 levels were decreased significantly 2 h after skin incision compared to
      the preoperative levels returning to preoperative levels at 6 h. A highly
      significant (P<0.0001) maximum level was observed 1 day after surgery and was
      decreasing to preoperative levels 30 days after surgery. Patients undergoing
      laparoscopically assisted or open resection had similar TIMP-1 levels at each
      time point. CONCLUSIONS: Major surgery has considerable impact on plasma TIMP-1
      levels. Intra- and post-operative changes of plasma TIMP-1 levels are independent
      of the surgical approach, and resection for CC does not lead to a significant
      decrease of plasma TIMP-1 levels within 30 days postoperatively.

PMID- 16466555
TI  - Prospective study on the management of patients with complicated diverticular
      disease.
AB  - INTRODUCTION: Diverticular disease is a common condition with high morbidity and
      mortality related to its complications. The aim of this study was to assess the
      predictive role of acute diverticulitis in the development of further
      complications from diverticular disease. PATIENTS AND METHODS: Prospective
      assessment of all patients with complicated diverticular disease over a 1-year
      period in a large teaching hospital was undertaken. All patients had documented
      evidence of their diagnosis by radiological, endoscopic or histopathological
      techniques when feasible. RESULTS: Seventy-seven patients with complicated
      diverticular disease were identified. There were 53 females and 24 males with a
      median age of 74 years (range 30-97 years). Complications included: acute
      diverticulitis (37), fistula (12), perforation (8), bleeding (7), abscess (7) and
      stricture (6). Only 8 had two or more previous documented episodes of
      diverticulitis. Twenty-five underwent surgery, 3 died (peritonitis 2, abscess1)
      and 5 had a complication (anastomotic dehiscence 1, adhesive obstruction 1,
      incisional hernia 2 and pneumonia 1). Three (5%) of 37 patients with acute
      diverticulitis had two or more admissions but none underwent surgery or developed
      further complications. CT was performed during acute admission in 14/37 patients
      with acute diverticulitis. The majority of patients with fistula (9/12),
      perforation 7/8, bleeding 6/7 and abscess 5/7 had no previous episode of
      diverticulitis while most patients with stricture (4/6) had previous documented
      episodes. CONCLUSION: In our patient population acute diverticulitis is not a
      good predictor of the development of further complications from diverticular
      disease as only a minority of patients with perforation, fistula, abscess and
      bleeding had previous documented episodes of diverticulitis.

PMID- 16466556
TI  - Surgery and pre-operative irradiation for locally advanced or recurrent rectal
      cancer in patients over 75 years of age.
AB  - OBJECTIVE: Reports of multimodal treatment regimens especially focusing on
      locally advanced or recurrent rectal cancer in the elderly, aged>75 years, are
      unavailable. We have tried to identify and evaluate pre- and peri-operative risk
      factors for morbidity and mortality and outcome after irradiation/surgery
      regimens in such patients. PATIENTS AND METHODS: Prospective registration of 86
      consecutive patients aged>75 years undergoing elective surgery after irradiation
      46-50 Gy for either primary locally advanced rectal cancer (n=51) or recurrent
      rectal cancer (n=35) from January 1991 to August 2003, 51 men and 35 women,
      median age 78 years (range 75-85 years) in a national cancer hospital. RESULTS:
      Multivisceral resections were needed in 63% of patients and 70% R0 resections
      were obtained in locally advanced cases and 46% in recurrent ones. Both in
      hospital- and 30-day-mortality was 3.5%. Sixty-two postoperative complications
      occurred in 38 patients, three of them fatal. Both operation times over 5 h and
      transfusion of more than 3 SAG were prognostic factors regarding infections.
      Estimated five-year survival in R0 patients was 46%. Estimated five-year survival
      for patients with nonmetastatic tumours with locally advanced primary cancer was
      29% and for locally recurrent rectal cancer 32%. Old males had a higher mortality
      rate the first year after surgery than females with only 65% relative survival
      compared to a matched normal population. The estimated five-year local recurrence
      rates were 24% for R0 resections and 54% for R1 resections (P=0.434 ns) and 24%
      and 45% for locally advanced and recurrent rectal cancer (P=0.248 ns),
      respectively. CONCLUSION: Thorough pre-operative evaluation and preparation and
      judicious surgery are important for achieving potentially curative treatment with
      acceptable morbidity in locally advanced and recurrent rectal cancer in patients
      over 75 years of age. We suggest that these patients should be evaluated and
      considered for treatment by multidisciplinary teams as younger patients.

PMID- 16466557
TI  - Patients' expectations of colorectal surgery for cancer.
AB  - OBJECTIVE: The primary objectives of surgery for colorectal cancer are to achieve
      radical resection of the tumour and to ensure a satisfactory quality of life for
      the patient. But what is satisfactory quality of life for the patients? What do
      patients desire? The goal of our exploratory investigation was to evaluate
      prospectively the patient pre-operative expectations as objectively as possible
      and to analyse results in relation to age, gender and socio-economic status.
      METHODS: In the period from 1998 to 2001, 167 patients were given a questionnaire
      consisting of 15 questions prior to surgery. The questionnaire included various
      aspects that were thought to influence the patient's quality of life. Moreover
      the patients were given the opportunity to rate the questions they considered
      most important. RESULTS: The following five points were considered most important
      by the total group of patients: Complete cure of the disease was rated most
      important (95%); it was the prime expectation of the patients. This was followed
      by the avoidance of a stoma (81%), a reliable control of defaecation (52%),
      normal digestion (44%) and little pain (26%). CONCLUSION: Age, gender and
      education influence the pre-operative expectations of patients undergoing surgery
      for colorectal cancer. In addition to the surgical standard, the care of the
      individual patient must be given due consideration in the treatment strategy.

PMID- 16466558
TI  - The routine use of intra-operative ultrasound in patients with colorectal cancer
      improves the detection of hepatic metastases.
AB  - INTRODUCTION: Up to one fifth of patients with carcinoma of the colon have occult
      liver metastases at the time of presentation. Intra-operative hepatic
      ultrasonography might improve disease staging. We report the use of intra
      operative ultrasonography (IOUS) in routine clinical practice over a five-year
      period. METHOD: Seventy-six patients with colorectal carcinoma (F 21, M 55) of
      median age 67 years (range 43-89 years) for whom full data were available had
      IOUS at the time of colonic resection. All patients had had a computerized
      tomography (CT), magnetic resonance imaging (MRI) or ultrasonography (USS).
      RESULTS: Of 76 patients, 10 had a Dukes A, 32 had a Dukes B and 34 a Dukes C
      carcinoma. In 20 patients IOUS detected lesions not seen on pre-operative
      scanning including 11 metastases (one suitable for resection), seven benign
      hepatic cysts and two were benign hepatic nodules. Forty-nine patients have
      remained free of disease and 25 have died with systemic disease (mean survival 10
      months, range 2-24 months). In the seven patients diagnosed as having hepatic
      cysts at IOUS two have died of systemic disease. The remaining patients (n=12)
      who died with systemic disease had a negative IOUS. CONCLUSION: IOUS increases
      diagnostic yield but a significant proportion of patients with occult hepatic
      metastases are not detected. IOUS improves disease staging in some patients
      refining the indications for adjuvant therapy and enhancing the estimate of
      prognosis and improving decision-making.

PMID- 16466559
TI  - Aetiology and surgical management of toxic megacolon.
AB  - OBJECTIVE: The purpose of this article is to review the surgical management and
      outcome of toxic megacolon and to update the aetiology of toxic megacolon.
      PATIENTS AND METHOD: A retrospective chart review of three academic colorectal
      surgery units was undertaken. Over a period of 20 years, 70 patients with
      surgically managed toxic megacolon were identified: 32 men and 38 women, median
      age 63 years (range, 23-87 years). RESULTS: In 33 (48%) patients the main cause
      of toxic megacolon was inflammatory bowel disease. Thirty-seven (52%) patients
      had toxic megacolon of different aetiology. Sixty-three patients underwent
      colonic resection: 49 (70%) subtotal colectomies and 14 (20%) total colectomies,
      including 4 (6%) proctocolectomies. Seven (10%) patients had decompression (n=3)
      or faecal diversion (n=4) only. Forty-four of the resected patients underwent a
      Hartmann's procedure and an ileostomy; 13 (19%) patients had primary anastomoses,
      11 (16%) ileorectal anastomoses (IRA) and 2 (3%) patients had ileal pouch-anal
      anastomosis (IPAA). Twenty-six (37%) patients subsequently had continuity
      restored. Total surgical complication rate was 19% (n=13), 8% (n=4) in patients
      treated with subtotal colectomy, 21% (n=3) in patients treated with total
      proctocolectomy and 86% (n=6) in patients treated with either decompression or
      diversion. The total mortality rate was 16% (n=11). CONCLUSIONS: Toxic colitis
      complicated by toxic megacolon can occur after various diseases of the colon and
      remains a life-threatening disorder associated with a significant risk of
      postoperative complications. Subtotal colectomy with ileostomy remains the
      procedure of choice. Surgical colonic decompression with faecal diversion alone
      is associated with a high rate of complications.

PMID- 16466560
TI  - Diagnostic accuracy of body coil MRI in describing the characteristics of
      perianal fistulas.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy of synergic
      body coil MRI using SPIR technique without contrast, in the determination of
      fistula characteristics in patients with clinically positive signs. METHOD AND
      SUBJECTS: This was a case-series prospective study including 29 consecutive
      patients with clinically suspected fistulas-in-ano. The standard synergic body
      coil was used and all patients had T2-weighted SPIR sequences. One radiologist,
      without prior knowledge of the clinical examination, analysed images and noted
      the presence of the fistula, its classification and the presence and number of
      any collections or extensions. The surgeon noted the MRI findings and looked for
      lesions suggested on MRI. The results of the MRI and surgical assessments were
      then compared. Results of surgical exploration while the surgeon was aware of MRI
      results were considered as the gold standard of surgical anatomy. RESULTS: Twenty
      three (79.31%) of 29 fistula tracks were seen on MRI which correctly determined
      the type of all fistulas. In the six cases where the fistula was not seen on MRI,
      five were low trans-sphincteric and one was rectovaginal. MRI identified 8 of 10
      collections. CONCLUSION: The synergic body coil MRI with SPIR sequencing without
      endoanal coils had a high accuracy in the diagnosis of high fistulas collections,
      complex fistulas and extensions.

PMID- 16466561
TI  - Evaluation of knowledge and anxiety level of patients visiting the colorectal
      pelvic floor clinic.
AB  - OBJECTIVE: Discussing defaecating disorders is difficult for patients and many
      view anal physiology investigations (ultrasound, manometry, electromyography and
      pudendal nerve studies) as distasteful. This pilot study sought to assess whether
      present information sheets supplied to patients and the visit to the colorectal
      Pelvic Floor Clinic itself influenced patients' knowledge and anxiety. PATIENTS
      AND METHODS: Thirty Pelvic Floor Clinic patients from Auckland City Hospital were
      included. Each patient filled in a questionnaire before and after the clinic.
      This included objective questions about their knowledge of the structure and
      function of the pelvic floor and satisfaction with and understanding of the
      information sheet. Both visual analogue scale (VAS) and multiple choice questions
      (MCQ) were used. Their subjective and objective knowledge were compared. Anxiety
      was assessed on a visual analogue anxiety scale (VAAS). Results were expressed as
      VAS scores or percentage correct and relationships were tested using Fisher's
      Exact test and paired T-test. RESULTS: Subjective knowledge increased in 93% of
      the patients. The doctor's explanation led to a greater increase in subjective
      knowledge than the information sheet (35/100 mm, P<0.001 and 10/100 mm, P=0.01,
      respectively). Subjective improvement in knowledge did not however, translate
      into an increase in objective knowledge (P=0.63). The information sheet was read
      by 87% of the patients. The information sheet had reduced anxiety only in 23% of
      the patients and increased in 10%. Anxiety levels were not significantly
      influenced by the information sheet, but reduced significantly by the clinic
      visit in 87% of patients (P<0.001). The mean anxiety level reduced from 44/100 to
      12/100 after the clinic visit. CONCLUSION: Anxiety levels are high in those
      visiting the Pelvic Floor Clinic. It appears that it is the interaction with the
      doctor that has a profound influence on anxiety levels and subjective knowledge
      rather than written information.

PMID- 16466562
TI  - Postoperative arrhythmias in colorectal surgical patients: incidence and clinical
      correlates.
AB  - OBJECTIVE: To determine the incidence and clinical correlates of postoperative
      cardiac arrhythmias in patients undergoing elective large bowel resection.
      METHODS: Fifty-one consecutive patients undergoing elective open colorectal
      resection were recruited for this prospective observational study. Participating
      patients underwent daily three-lead electrocardiograms postoperatively. Data
      regarding potential risk factors for arrhythmias were recorded. Post-operative
      complications were recorded. RESULTS: Thirteen (26%) patients developed a
      postoperative arrhythmia, most commonly atrial fibrillation. Significant
      univariate correlates with postoperative arrhythmias were: age (P<0.01),
      hypertension (P<0.01), pre-operative serum potassium levels (P<0.01),
      postoperative pulmonary oedema (P=0.03), postoperative serum potassium (P=0.03)
      and sodium (P<0.01). Arrhythmia patients were more likely to have other
      complications (P=0.02). Thirty-one percent of arrhythmia patients had underlying
      sepsis compared with 18% of controls (P=0.38). CONCLUSION: Arrhythmias are common
      following elective large bowel resection. They occur in older patients and are
      associated with the development of other complications.

PMID- 16466563
TI  - A critical appraisal of internet resources on colorectal cancer.
AB  - OBJECTIVE: The significance of the internet as a source of healthcare information
      for professionals and public is widely recognized. Access to good quality
      information is very important for informed decisions making on healthcare issues.
      This is an introduction to the critical appraisal of clinical information on the
      internet, discussion of the significance of quality checking of healthcare
      internet resources and the application of critical appraisal tools to selected
      internet resources on colorectal cancer care. METHODS: Internet resources were
      identified on the basis of a general criterion that it provides information on
      colorectal cancer and selected on the basis of explicit inclusion and exclusion
      criteria. Each selected website is assessed for quality of information with
      validated criteria. RESULTS: The search strategy identified 10 well known
      internet resources on healthcare information (e.g. Cochrane, NICE) and 12
      websites which are dedicated to cancer related information (e.g. CancerBacup,
      cancer.gov). The websites of NHS Direct, cancerBACUP, cancer.gov, NICE and Cancer
      Survivors Network were qualified as resources providing good quality information.
      DISCUSSION: The critical appraisal process assures quality of the available
      information and the tool is applicable to all healthcare related internet
      resources. The process is discussed with respect to colorectal cancer information
      resources and will be equally useful to healthcare professional and public. The
      healthcare professionals can apply the tool in practice and advise the public
      more confidently on internet information.

PMID- 16466564
TI  - Nationwide quality assurance of rectal cancer treatment.
AB  - OBJECTIVE: The purpose of this prospective study was to examine the influence of
      the efforts for nationwide quality assurance of rectal cancer treatment. The
      study focuses on local recurrence and overall survival. METHODS: This study
      includes all 3388 Norwegian patients with a rectal cancer within 15 cm from the
      anal verge treated with curative intent in the period November 1993-December
      1999. A comprehensive educational programme was established, and training courses
      were arranged in different Health Regions demonstrating the TME technique. A
      specific Rectal Cancer Registry enabled the monitoring of outcome of rectal
      cancer treatment for single hospitals. Radiotherapy was given to 10% of the
      patients. RESULTS: The risk of local recurrence has been significantly reduced,
      so that in 1999 the level was 50% below that observed in 1994 (Hazard ratio
      (HR)1999=0.5; 95% CI 0.4-0.8, P=0.002). Similarly, during 1998, the mean national
      overall survival was significantly improved, compared to the rate in 1994
      (HR1998=0.8; 95% CI 0.6-1.0, P=0.014). CONCLUSION: The prognosis for rectal
      cancer can be improved by increased organizational focus on rectal cancer
      treatment and by establishing a rectal cancer registry monitoring treatment
      standards throughout the country.

PMID- 16466565
TI  - Changes in vasoconstrictor and vasodilator neurotransmitters in nerves supplying
      arterioles in developing colorectal polyps.
AB  - OBJECTIVE: To examine the changes that occur in the immunohistochemistry of
      vasoconstrictor and vasodilator transmitters in nerves supplying early and
      advanced colorectal polyps. SUBJECTS AND METHODS: We studied the perivascular
      innervation of submucosal arterioles of colorectal polyps (n = 18) and the
      innervation of the epithelial layer of polyps compared to normal controls (n=8),
      using immunohistochemical markers for the neurotransmitters; noradrenaline (NA)
      (marker used; tyrosine hydroxylase (TH)), neuropeptide Y (NPY), vasoactive
      intestinal polypeptide (VIP), substance P (SP), and calcitonin gene-related
      polypeptide (CGRP). (Advanced polyps; villous adenomas>1.5 cm, polyps with severe
      dysplasia or partial carcinoma). RESULTS: In submucosal arterioles there was a
      progressive decrease from controls through early polyps to advanced polyps in TH
      and NPY perivascular immunoreactivity (P<0.015 for both). VIP and SP
      immunoreactivity was higher in early polyps compared to controls, but markedly
      reduced in advanced polyps (P<0.05 for VIP). Sparse CGRP immunoreactivity was
      present in polyps only. Neural VIP and SP immunoreactivity in the lamina propria
      of polyp mucosa was more intense than in controls. CONCLUSION: There is a
      decrease in vasoconstrictor neurotransmitters NPY and NA (shown by TH) around
      submucosal arterioles of both early and advanced polyps, but an increase in the
      vasodilator neurotransmitters, particularly VIP, in early colorectal polyps.
      These results suggest a predominantly vasodilatory neural influence in early
      polyps, perhaps indicating a mechanism that maintains polyp growth.

PMID- 16466566
TI  - Ileal pouch anal anastomosis for ulcerative colitis is feasible for
      septuagenarians.
AB  - OBJECTIVE: Proctocolectomy and ileal pouch anal anastomosis (IPAA) has become the
      standard surgery for patients with mucosal ulcerative colitis (MUC). Although
      there is no absolute age limitation, there are concerns as to its use in elderly
      patients due to the risks of potential complications and poor function. The aim
      of this study was to assess the complications and outcome of patients over the
      age of 70 years with MUC who underwent IPAA. Results in these patients were
      compared to the results in a group of patients aged less than 70 years who had
      IPAA. METHODS: After Institutional Review Board approval, a retrospective review
      of the medical records of patients with MUC who underwent IPAA was undertaken.
      These patients were divided into four age groups: <30 years of age, 30-49 years,
      50-69 years, >or=70 years. RESULTS: From 1989 to 2001, 330 patients underwent
      IPAA for preoperative clinical and histopathological and postoperative
      histopathologically confirmed MUC; 17 were aged>or=70 years. The mean hospital
      stay was 5.8 (SEM 0.7) days in the patients aged<70 years and 6.0 (SEM 0.4) days
      in the patients aged>or=70 years (P=0.911). Postoperative complications occurred
      in 39% of patients>or=70 years and in 40% in the <70 years group (P=0.08). Pouch
      failure occurred in two (11.8%) patients>or=70 years and in 6 (1.9%)<70 (P=0.2).
      CONCLUSION: IPAA is a safe and feasible option in MUC patients over the age of 70
      with functional results similar to results seen in younger patients.

PMID- 16466567
TI  - Intestinal obstruction and perforation caused by defunctioning the wrong end of
      the bowel-an impossible complication?

PMID- 16466568
TI  - BAMarraytrade mark: Java software for Bayesian analysis of variance for
      microarray data.
AB  - BACKGROUND: DNA microarrays open up a new horizon for studying the genetic
      determinants of disease. The high throughput nature of these arrays creates an
      enormous wealth of information, but also poses a challenge to data analysis.
      Inferential problems become even more pronounced as experimental designs used to
      collect data become more complex. An important example is multigroup data
      collected over different experimental groups, such as data collected from
      distinct stages of a disease process. We have developed a method specifically
      addressing these issues termed Bayesian ANOVA for microarrays (BAM). The BAM
      approach uses a special inferential regularization known as spike-and-slab
      shrinkage that provides an optimal balance between total false detections and
      total false non-detections. This translates into more reproducible differential
      calls. Spike and slab shrinkage is a form of regularization achieved by using
      information across all genes and groups simultaneously. RESULTS: BAMarray is a
      graphically oriented Java-based software package that implements the BAM method
      for detecting differentially expressing genes in multigroup microarray
      experiments (up to 256 experimental groups can be analyzed). Drop-down menus
      allow the user to easily select between different models and to choose various
      run options. BAMarraycan also be operated in a fully automated mode with
      preselected run options. Tuning parameters have been preset at theoretically
      optimal values freeing the user from such specifications. BAMarray provides
      estimates for gene differential effects and automatically estimates data
      adaptive, optimal cutoff values for classifying genes into biological patterns of
      differential activity across experimental groups. A graphical suite is a core
      feature of the product and includes diagnostic plots for assessing model
      assumptions and interactive plots that enable tracking of prespecified gene lists
      to study such things as biological pathway perturbations. The user can zoom in
      and lasso genes of interest that can then be saved for downstream analyses.
      CONCLUSION: BAMarray is user friendly platform independent software that
      effectively and efficiently implements the BAM methodology. Classifying patterns
      of differential activity is greatly facilitated by a data adaptive cutoff rule
      and a graphical suite. BAMarray is licensed software freely available to academic
      institutions. More information can be found at http://www.bamarray.com.

PMID- 16466569
TI  - Identifying biological concepts from a protein-related corpus with a
      probabilistic topic model.
AB  - BACKGROUND: Biomedical literature, e.g., MEDLINE, contains a wealth of knowledge
      regarding functions of proteins. Major recurring biological concepts within such
      text corpora represent the domains of this body of knowledge. The goal of this
      research is to identify the major biological topics/concepts from a corpus of
      protein-related MEDLINE titles and abstracts by applying a probabilistic topic
      model. RESULTS: The latent Dirichlet allocation (LDA) model was applied to the
      corpus. Based on the Bayesian model selection, 300 major topics were extracted
      from the corpus. The majority of identified topics/concepts was found to be
      semantically coherent and most represented biological objects or concepts. The
      identified topics/concepts were further mapped to the controlled vocabulary of
      the Gene Ontology (GO) terms based on mutual information. CONCLUSION: The major
      and recurring biological concepts within a collection of MEDLINE documents can be
      extracted by the LDA model. The identified topics/concepts provide parsimonious
      and semantically-enriched representation of the texts in a semantic space with
      reduced dimensionality and can be used to index text.

PMID- 16466572
TI  - Direct interaction between the catalytic subunit of Protein Phosphatase 1 and
      pRb.
AB  - BACKGROUND: The product of the retinoblastoma-susceptibility gene (pRb) is a
      substrate for Protein Phosphatase 1 (PP1). At mitotic exit, all three PP1
      isoforms, alpha, gamma1 and delta, bind to pRb and dephosphorylate its Ser/Thr
      sites in a sequential and site-specific way. The pRb-C terminal has been reported
      to be necessary and sufficient for PP1alpha binding. The present study
      investigated whether the three PP1 isoforms from mitotic or asynchronous HeLa
      cells associate differentially with wild-type and pRb mutants, as well as the
      holoenzyme composition of the pRb-directed PP1. RESULTS: The requirement for the
      entire pRb molecule to achieve optimal PP1-binding was indicated by the fact that
      full-length pRb displayed the highest affinity for all three PP1 isoforms.
      Ser/Thr-to-Ala substitution for up to 14 pRb sites did not affect the ability of
      pRb to bind the PP1 isoforms derived from mitotic or asynchronous HeLa cells,
      thus suggesting that the phosphate-accepting residues on pRb do not regulate the
      interaction with PP1. To probe for the presence of PP1 targeting subunits in the
      pRb-directed PP1 complex, PP1 from mitotic or asynchronous HeLa cells was
      isolated by affinity chromatography on GST-Rb (either full-length or its deletion
      mutants Rb-big pocket or Rb-C-terminal). The PP1 was always obtained as free
      catalytic subunit, displaying all three isoforms, thus suggesting direct
      interaction between pRb and PP1. The direct association was confirmed by the
      ability of pRb to pull-down purified PP1 catalytic subunits and by in vitro
      reconstitution of a complex between PP1 catalytic subunit and the pRb-C-terminal.
      CONCLUSION: The work indicated that the full length of the pRb molecule is
      required for optimal interaction with the PP1 isoforms and that the association
      between pRb and PP1 isoforms is direct.

PMID- 16466571
TI  - The 18 Household Food Security Survey items provide valid food security
      classifications for adults and children in the Caribbean.
AB  - BACKGROUND: We tested the properties of the 18 Household Food Security Survey
      (HFSS) items, and the validity of the resulting food security classifications, in
      an English-speaking middle-income country. METHODS: Survey of primary school
      children in Trinidad and Tobago. Parents completed the HFSS. Responses were
      analysed for the 10 adult-referenced items and the eight child-referenced items.
      Item response theory models were fitted. Item calibrations and subject scores
      from a one-parameter logistic (1PL) model were compared with those from either
      two-parameter logistic model (2PL) or a model for differential item functioning
      (DIF) by ethnicity. RESULTS: There were 5219 eligible with 3858 (74%) completing
      at least one food security item. Adult item calibrations (standard error) in the
      1PL model ranged from -4.082 (0.019) for the 'worried food would run out' item to
      3.023 (0.042) for 'adults often do not eat for a whole day'. Child item
      calibrations ranged from -3.715 (0.025) for 'relied on a few kinds of low cost
      food' to 3.088 (0.039) for 'child didn't eat for a whole day'. Fitting either a
      2PL model, which allowed discrimination parameters to vary between items, or a
      differential item functioning model, which allowed item calibrations to vary
      between ethnic groups, had little influence on interpretation. The classification
      based on the adult-referenced items showed that there were 19% of respondents who
      were food insecure without hunger, 10% food insecure with moderate hunger and 6%
      food insecure with severe hunger. The classification based on the child
      referenced items showed that there were 23% of children who were food insecure
      without hunger and 9% food insecure with hunger. In both children and adults food
      insecurity showed a strong, graded association with lower monthly household
      income (P < 0.001). CONCLUSION: These results support the use of 18 HFSS items to
      classify food security status of adults or children in an English-speaking
      country where food insecurity and hunger are more frequent overall than in the
      US.

PMID- 16466570
TI  - Influence of head models on EEG simulations and inverse source localizations.
AB  - BACKGROUND: The structure of the anatomical surfaces, e.g., CSF and gray and
      white matter, could severely influence the flow of volume currents in a head
      model. This, in turn, will also influence the scalp potentials and the inverse
      source localizations. This was examined in detail with four different human head
      models. METHODS: Four finite element head models constructed from segmented MR
      images of an adult male subject were used for this study. These models were: (1)
      Model 1: full model with eleven tissues that included detailed structure of the
      scalp, hard and soft skull bone, CSF, gray and white matter and other prominent
      tissues, (2) the Model 2 was derived from the Model 1 in which the conductivity
      of gray matter was set equal to the white matter, i.e., a ten tissue-type model,
      (3) the Model 3 was derived from the Model 1 in which the conductivities of gray
      matter and CSF were set equal to the white matter, i.e., a nine tissue-type
      model, (4) the Model 4 consisted of scalp, hard skull bone, CSF, gray and white
      matter, i.e., a five tissue-type model. How model complexity influences the EEG
      source localizations was also studied with the above four finite element models
      of the head. The lead fields and scalp potentials due to dipolar sources in the
      motor cortex were computed for all four models. The inverse source localizations
      were performed with an exhaustive search pattern in the motor cortex area. The
      inverse analysis was performed by adding uncorrelated Gaussian noise to the scalp
      potentials to achieve a signal to noise ratio (SNR) of -10 to 30 dB. The Model 1
      was used as a reference model. RESULTS: The reference model, as expected,
      performed the best. The Model 3, which did not have the CSF layer, performed the
      worst. The mean source localization errors (MLEs) of the Model 3 were larger than
      the Model 1 or 2. The scalp potentials were also most affected by the lack of CSF
      geometry in the Model 3. The MLEs for the Model 4 were also larger than the Model
      1 and 2. The Model 4 and the Model 3 had similar MLEs in the SNR range of -10 dB
      to 0 dB. However, in the SNR range of 5 dB to 30 dB, the Model 4 has lower MLEs
      as compared with the Model 3. DISCUSSION: These results indicate that the
      complexity of head models strongly influences the scalp potentials and the
      inverse source localizations. A more complex head model performs better in
      inverse source localizations as compared to a model with lesser tissue surfaces.
      The CSF layer plays an important role in modifying the scalp potentials and also
      influences the inverse source localizations. In summary, for best results one
      needs to have highly heterogeneous models of the head for accurate simulations of
      scalp potentials and for inverse source localizations.

PMID- 16466574
TI  - Understanding the attitudes of the elderly towards enrolment into cancer clinical
      trials.
AB  - BACKGROUND: The optimal cancer treatment for an older population is largely
      unknown because of the low numbers of elderly patients accrued into clinical
      trials. This project focuses on the attitudes of the elderly about participation
      in clinical trials to determine if this is one of the barriers to the involvement
      of this population in clinical trials. METHODS: The first phase of this study was
      a self-administered questionnaire mailed to 425 elderly persons with cancer,
      selected from Princess Margaret Hospital oncology clinics. The second phase
      consisted of individual semi-structured interviews with cancer patients to assess
      their attitudes towards cancer, its management and enrolment into cancer clinical
      trials. RESULTS: Ninety-four patients responded to the survey giving a response
      rate of 22.1%. Three quarters of respondents stated that they would be willing to
      participate in a clinical trial. The factors that most influenced older patients'
      willingness to participate in a cancer study were recommendations from a cancer
      doctor and the chance that the study treatment may help them feel better.
      Seventeen survey responders participated in interviews. Common themes from these
      interviews included patient-physician communication, the referral process, and
      the role of age in cancer care decision-making. CONCLUSION: Most elderly people,
      who responded to this survey, are willing to consider participation in cancer
      clinical trials however, elderly patients do not appear to actively seek clinical
      trials and few were informed of the availability of clinical trials. Physician
      barriers and availability of appropriate clinical trials may play a bigger role
      in preventing accrual of elderly cancer patients into trials.

PMID- 16466573
TI  - Auditory change detection in schizophrenia: sources of activity, related
      neuropsychological function and symptoms in patients with a first episode in
      adolescence, and patients 14 years after an adolescent illness-onset.
AB  - BACKGROUND: The event-related brain response mismatch negativity (MMN) registers
      changes in auditory stimulation with temporal lobe sources reflecting short-term
      echoic memory and frontal sources a deviance-induced switch in processing.
      Impairment, controversially present at the onset of schizophrenia, develops
      rapidly and can remain independent of clinical improvement. We examined the
      characteristics of the scalp-recorded MMN and related these to tests of short
      term memory and set-shifting. We assessed whether the equivalent dipole sources
      are affected already at illness-onset in adolescence and how these features
      differ after a 14-year course following an adolescent onset. The strength,
      latency, orientation and location of frontal and temporal lobe sources of MMN
      activity early and late in the course of adolescent-onset schizophrenia are
      analysed and illustrated. METHODS: MMN, a measure of auditory change-detection,
      was elicited by short deviant tones in a 3-tone oddball-presentation and recorded
      from 32 scalp electrodes. Four dipole sources were placed following hypothesis
      led calculations using brain electrical source analysis on brain atlas and MR
      images. A short neuropsychological test battery was administered. We compared 28
      adolescent patients with a first episode of schizophrenia and 18 patients 14
      years after diagnosis in adolescence with two age-matched control groups from the
      community (n = 22 and 18, respectively). RESULTS: MMN peaked earlier in the
      younger than the older subjects. The amplitude was reduced in patients,
      especially the younger group, and was here associated with negative symptoms and
      slow set-shifting. In first-episode patients the temporal lobe sources were more
      ventral than in controls, while the left cingular and right inferior-mid frontal
      sources were more caudal. In the older patients the left temporal locus remained
      ventral (developmental stasis), the right temporal locus extended more antero
      laterally (illness progression), and the right frontal source moved antero
      laterally (normalised). CONCLUSION: From the start of the illness there were
      differences in the dipole-model between healthy and patient groups. Separate
      characteristics of the sources of the activity differences showed an improvement,
      stasis or deterioration with illness-duration. The precise nature of the changes
      in the sources of MMN activity and their relationship to selective information
      processing and storage depend on the specific psychopathology and heterogeneous
      course of the illness.

PMID- 16466576
TI  - Uncharged isocoumarin-based inhibitors of urokinase-type plasminogen activator.
AB  - BACKGROUND: Urokinase-type plasminogen activator (uPA) plays a major role in
      extracellular proteolytic events associated with tumor cell growth, migration and
      angiogenesis. Consequently, uPA is an attractive target for the development of
      small molecule active site inhibitors. Most of the recent drug development
      programs aimed at nonpeptidic inhibitors targeted at uPA have focused on arginino
      mimetics containing amidine or guanidine functional groups attached to aromatic
      or heterocyclic scaffolds. There is a general problem of limited bioavailability
      of these charged inhibitors. In the present study, uPA inhibitors were designed
      on an isocoumarin scaffold containing uncharged substituents. RESULTS: 4-Chloro-3
      alkoxyisocoumarins were synthesized in which the 3-alkoxy group contained a
      terminal bromine; these were compared with similar inhibitors that contained a
      charged terminal functional group. Additional variations included functional
      groups attached to the seven position of the isocoumarin scaffold. N- [3-(3
      Bromopropoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide was identified as an
      uncharged lead inhibitor of uPA, Ki = 0.034 microM. Molecular modeling of human
      uPA with these uncharged inhibitors suggests that the bromine occupies the same
      position as positively charged arginino mimetic groups. CONCLUSION: This study
      demonstrates that potent uncharged inhibitors of uPA can be developed based upon
      the isocoumarin scaffold. A tethered bromine in the three position and an
      aromatic group in the seven position are important contributors to binding.
      Although the aim was to develop compounds that act as mechanism-based
      inactivators, these inhibitors are competitive reversible inhibitors.

PMID- 16466577
TI  - Sebaceous gland tumors and internal malignancy in the context of Muir-Torre
      syndrome. A case report and review of the literature.
AB  - BACKGROUND: The Muir-Torre syndrome is a rare autosomal dominant condition and is
      currently considered a subtype of the more common hereditary nonpolyposis
      colorectal cancer syndrome, in which multiple primary malignancies occur together
      with sebaceous gland tumors. CASE PRESENTATION: We describe a case of a 62-year
      old woman with three primary colorectal tumors, genital tumor, and sebaceous
      adenomas and present her family history of three generations. Our case represents
      the first case reported from Greece in the international literature. CONCLUSION:
      Recognition of the syndrome in patients with sebaceous gland tumors should
      facilitate early detection of subsequent malignancies if the patient is entered
      into appropriate screening programs.

PMID- 16466575
TI  - Many genes in fish have species-specific asymmetric rates of molecular evolution.
AB  - BACKGROUND: Gene and genome duplication events increase the amount of genetic
      material that might then contribute to an increase in the genomic and phenotypic
      complexity of organisms during evolution. Thus, it has been argued that there is
      a relationship between gene copy number and morphological complexity and/or
      species diversity. This hypothesis implies that duplicated genes have subdivided
      or evolved novel functions compared to their pre-duplication proto-orthologs.
      Such a functional divergence might be caused by an increase in evolutionary rates
      in one ortholog, by changes in expression, regulatory evolution, insertion of
      repetitive elements, or due to positive Darwinian selection in one copy. We
      studied a set of 2466 genes that were present in Danio rerio, Takifugu rubripes,
      Tetraodon nigroviridis and Oryzias latipes to test (i) for forces of positive
      Darwinian selection; (ii) how frequently duplicated genes are retained, and (iii)
      whether novel gene functions might have evolved. RESULTS: 25% (610) of all
      investigated genes show significantly smaller or higher genetic distances in the
      genomes of particular fish species compared to their human ortholog than their
      orthologs in other fish according to relative rate tests. We identified 49 new
      paralogous pairs of duplicated genes in fish, in which one of the paralogs is
      under positive Darwinian selection and shows a significantly higher rate of
      molecular evolution in one of the four fish species, whereas the other copy
      apparently did not undergo adaptive changes since it retained the original rate
      of evolution. Among the genes under positive Darwinian selection, we found a
      surprisingly high number of ATP binding proteins and transcription factors.
      CONCLUSION: The significant rate difference suggests that the function of these
      rate-changed genes might be essential for the respective fish species. We
      demonstrate that the measurement of positive selection is a powerful tool to
      identify divergence rates of duplicated genes and that this method has the
      capacity to identify potentially interesting candidates for adaptive gene
      evolution.

PMID- 16466579
TI  - Value of adenosine infusion for infarct size determination using real-time
      myocardial contrast echocardiography.
AB  - BACKGROUND: Myocardial contrast echocardiography has been used for determination
      of infarct size (IS) in experimental models. However, with intermittent harmonic
      imaging, IS seems to be underestimated immediately after reperfusion due to areas
      with preserved, yet dysfunctional, microvasculature. The use of exogenous
      vasodilators showed to be useful to unmask these infarcted areas with depressed
      coronary flow reserve. This study was undertaken to assess the value of adenosine
      for IS determination in an open-chest canine model of coronary occlusion and
      reperfusion, using real-time myocardial contrast echocardiography (RTMCE).
      METHODS: Nine dogs underwent 180 minutes of coronary occlusion followed by
      reperfusion. PESDA (Perfluorocarbon-Exposed Sonicated Dextrose Albumin) was used
      as contrast agent. IS was determined by RTMCE before and during adenosine
      infusion at a rate of 140 mcg.Kg(-1).min(-1). Post-mortem necrotic area was
      determined by triphenyl-tetrazolium chloride (TTC) staining. RESULTS: IS
      determined by RTMCE was 1.98 +/- 1.30 cm2 and increased to 2.58 +/- 1.53 cm2
      during adenosine infusion (p = 0.004), with good correlation between measurements
      (r = 0.91; p < 0.01). The necrotic area determined by TTC was 2.29 +/- 1.36 cm2
      and showed no significant difference with IS determined by RTMCE before or during
      hyperemia. A slight better correlation between RTMCE and TTC measurements was
      observed during adenosine (r = 0.99; p < 0.001) then before it (r = 0.92; p =
      0.0013). CONCLUSION: RTMCE can accurately determine IS in immediate period after
      acute myocardial infarction. Adenosine infusion results in a slight better
      detection of actual size of myocardial damage.

PMID- 16466581
TI  - Nurses' perceptions and experiences of communication in the operating theatre: a
      focus group interview.
AB  - Nurses' perceptions and experiences of communication in the operating theatre: a
      focus group interview BACKGROUND: Communication programmes are well established
      in nurse education. The focus of programmes is most often on communicating with
      patients with less attention paid to inter-professional communication or skills
      essential for working in specialised settings. Although there are many anecdotal
      reports of communication within the operating theatre, there are few empirical
      studies. This paper explores communication behaviours for effective practice in
      the operating theatre as perceived by nurses and serves as a basis for developing
      training. METHODS: A focus group interview was conducted with seven experienced
      theatre nurses from a large London teaching hospital. The interview explored
      their perceptions of the key as well as unique features of effective
      communication skills in the operating theatre. Data was transcribed and
      thematically analysed until agreement was achieved by the two authors. RESULTS:
      There was largely consensus on the skills deemed necessary for effective practice
      including listening, clarity of speech and being polite. Significant influences
      on the nature of communication included conflict in role perception and
      organisational issues. Nurses were often expected to work outside of their role
      which either directly or indirectly created barriers for effective communication.
      Perceptions of a lack of collaborative team effort also influenced communication.
      CONCLUSION: Although fundamental communication skills were identified for
      effective practice in the operating theatre, there were significant barriers to
      their use because of confusion over clarity of roles (especially nurses' roles)
      and the implications for teamwork. Nurses were dissatisfied with several aspects
      of communication. Future studies should explore the breadth and depth of this
      dissatisfaction in other operating theatres, its impact on morale and importantly
      on patient safety. Interprofessional communication training for operating theatre
      staff based in part on the key issues identified in this study may help to create
      clarity in roles and focus attention on effective teamwork and promote clinical
      safety.

PMID- 16466578
TI  - Merkel cell carcinoma.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an unusual primary neuroendocrine
      carcinoma of the skin. MCC is a fatal disease, and patients have a poor chance of
      survival. Moreover, MCC lacks distinguishing clinical features, and thus by the
      time the diagnosis is made, the tumour usually have metastasized. MCC mainly
      affects sun-exposed areas of elderly persons. Half of the tumours are located in
      the head and neck region. METHODS: MCC was first described in 1972. Since then,
      most of the cases reported, have been in small series of patients. Most of the
      reports concern single cases or epidemiological studies. The present study
      reviews the world literature on MCC. The purpose of this article is to shed light
      on this unknown neuroendocrine carcinoma and provide the latest information on
      prognostic markers and treatment options. RESULTS: The epidemiological studies
      have revealed that large tumour size, male sex, truncal site, nodal/distant
      disease at presentation, and duration of disease before presentation, are poor
      prognostic factors. The recommended initial treatment is extensive local
      excision. Adjuvant radiation therapy has recently been shown to improve survival.
      Thus far, no chemotherapy protocol have achieved the same objective. CONCLUSION:
      Although rare, the fatality of this malignancy makes is important to understand
      the etiology and pathophysiology. During the last few years, the research on MCC
      has produced prognostic markers, which can be translated into clinical patient
      care.

PMID- 16466582
TI  - Automated extraction protocol for quantification of SARS-coronavirus RNA in
      serum: an evaluation study.
AB  - BACKGROUND: We have previously developed a test for the diagnosis and prognostic
      assessment of the severe acute respiratory syndrome (SARS) based on the detection
      of the SARS-coronavirus RNA in serum by real-time quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR). In this study, we evaluated the
      feasibility of automating the serum RNA extraction procedure in order to increase
      the throughput of the assay. METHODS: An automated nucleic acid extraction
      platform using the MagNA Pure LC instrument (Roche Diagnostics) was evaluated. We
      developed a modified protocol in compliance with the recommended biosafety
      guidelines from the World Health Organization based on the use of the MagNA Pure
      total nucleic acid large volume isolation kit for the extraction of SARS
      coronavirus RNA. The modified protocol was compared with a column-based
      extraction kit (QIAamp viral RNA mini kit, Qiagen) for quantitative performance,
      analytical sensitivity and precision. RESULTS: The newly developed automated
      protocol was shown to be free from carry-over contamination and have comparable
      performance with other standard protocols and kits designed for the MagNA Pure LC
      instrument. However, the automated method was found to be less sensitive, less
      precise and led to consistently lower serum SARS-coronavirus concentrations when
      compared with the column-based extraction method. CONCLUSION: As the diagnostic
      efficiency and prognostic value of the serum SARS-CoV RNA RT-PCR test is
      critically associated with the analytical sensitivity and quantitative
      performance contributed both by the RNA extraction and RT-PCR components of the
      test, we recommend the use of the column-based manual RNA extraction method.

PMID- 16466583
TI  - Setting directions for capacity building in primary health care: a survey of a
      research network.
AB  - BACKGROUND: The South Australian Research Network 'SARNet' aims to build research
      capacity in primary health care, as part of a national government-funded strategy
      to integrate research into clinical practice. Internationally, research networks
      have been a fundamental part of research culture change, and a variety of network
      models exist. The 'SARNet' model uses a whole system, multidisciplinary approach
      to capacity building and supports individuals and groups. We undertook a
      descriptive baseline survey in order to understand the background and needs of
      SARNet members and to tailor network activities towards those needs. METHODS: A
      questionnaire survey, assessing members' professional background, research
      experience, and interest in research development and training, was sent to all
      members who joined the network in its first year. The visual 'research spider'
      tool was used to ascertain members' experience in ten core research skills, as
      well as their interest in developing these skills. Individuals were asked to
      classify themselves into one of four categories of researchers, based on previous
      research experience. These self-assessment categories ranged from non-participant
      to academic. RESULTS: Network membership was diverse. Of the 89 survey
      participants, 55% were general practitioners or allied health professionals.
      Overall, most survey respondents indicated little to moderate experience in 7 out
      of the 10 skills depicted in the 'research spider'. In comparison, respondents
      were generally highly interested in developing their research skills in all
      areas. Respondents' research skills correlated significantly with their self
      assessed category of research participation (Spearman rank correlation, r = 0.82,
      p < 0.0005). Correlations between research category and publication record (Gamma
      association, gamma = 0.53, p < 0.0005) or funding record (Gamma association,
      gamma = 0.62, p < 0.0005) supported the internal validity of the survey
      instrument. CONCLUSION: Literature describing evaluation of the impact of
      networks is scarce. Our survey questionnaire could provide a useful instrument
      for evaluation of both networks and capacity building initiatives. The survey
      including the 'research spider' tool provided valuable information about members'
      needs and interest in strategies to develop their research skills. Initial needs
      analyses as well as on-going evaluation of network activities are important to
      include into the business plans of research networks, in order to ensure the
      network's effectiveness and support of its membership.

PMID- 16466584
TI  - JLIN: a java based linkage disequilibrium plotter.
AB  - BACKGROUND: A great deal of effort and expense are being expended internationally
      in attempts to detect genetic polymorphisms contributing to susceptibility to
      complex human disease. Techniques such as Linkage Disequilibrium mapping are
      being increasingly used to examine and compare markers across increasingly large
      datasets. Visualisation techniques are becoming essential to analyse the ever
      growing volume of data and results available with any given analysis. RESULTS:
      JLIN (Java LINkage disequilibrium plotter) is a software package designed for
      customisable, intuitive visualisation of Linkage Disequilibrium (LD) across all
      common computing platforms. Customisation allows the user to choose particular
      visualisations, statistical measures and measurement ranges. JLIN also allows the
      user to export images of the LD visualisation in several common document formats.
      CONCLUSION: JLIN allows the user to visually compare and contrast the results of
      a range of statistical measures on the input dataset(s). These measures include
      the commonly used D' and r2 statistics and empirical p-values. JLIN has a number
      of unique and novel features that improve on existing LD visualisation tools.

PMID- 16466585
TI  - Comparative analysis of haplotype association mapping algorithms.
AB  - BACKGROUND: Finding the genetic causes of quantitative traits is a complex and
      difficult task. Classical methods for mapping quantitative trail loci (QTL) in
      miceuse an F2 cross between two strains with substantially different phenotype
      and an interval mapping method to compute confidence intervals at each position
      in the genome. This process requires significant resources for breeding and
      genotyping, and the data generated are usually only applicable to one phenotype
      of interest. Recently, we reported the application of a haplotype association
      mapping method which utilizes dense genotyping data across a diverse panel of
      inbred mouse strains and a marker association algorithm that is independent of
      any specific phenotype. As the availability of genotyping data grows in size and
      density, analysis of these haplotype association mapping methods should be of
      increasing value to the statistical genetics community. RESULTS: We describe a
      detailed comparative analysis of variations on our marker association method. In
      particular, we describe the use of inferred haplotypes from adjacent SNPs,
      parametric and nonparametric statistics, and control of multiple testing error.
      These results show that nonparametric methods are slightly better in the test
      cases we study, although the choice of test statistic may often be dependent on
      the specific phenotype and haplotype structure being studied. The use of multi
      SNP windows to infer local haplotype structure is critical to the use of a
      diverse panel of inbred strains for QTL mapping. Finally, because the marginal
      effect of any single gene in a complex disease is often relatively small, these
      methods require the use of sensitive methods for controlling family-wise error.
      We also report our initial application of this method to phenotypes cataloged in
      the Mouse Phenome Database. CONCLUSION: The use of inbred strains of mice for QTL
      mapping has many advantages over traditional methods. However, there are also
      limitations in comparison to the traditional linkage analysis from F2 and RI
      lines. Application of these methods requires careful consideration of algorithmic
      choices based on both theoretical and practical factors. Our findings suggest
      general guidelines, though a complete evaluation of these methods can only be
      performed as more genetic data in complex diseases becomes available.

PMID- 16466586
TI  - IPA survey of brief cognitive screening instruments.
AB  - BACKGROUND AND OBJECTIVES: Cognitive screening is a "first step" in detecting
      dementia and other neuropsychiatric syndromes and hence represents an important
      public health and clinical initiative. A plethora of cognitive screening
      instruments has been advocated in recent years, but the extent to which these
      instruments are used or their effectiveness is not well known. An International
      Psychogeriatric Association (IPA) survey was designed to determine which
      cognitive screening instruments were used most frequently by clinicians with
      special expertise in the neuropsychiatric aspects of old age and also to
      determine the ones considered most useful by these specialists. METHOD: Under the
      auspices of the IPA, the survey was mailed in the fall of 2004 to all IPA members
      as well as members of the American and Canadian Associations of Geriatric
      Psychiatry. The survey inquired about demographic information, the frequency of
      use of cognitive screening instruments, and the value attributed to the cognitive
      screening instruments. Participants also had an opportunity to provide written
      commentary. RESULTS: A total of 334 completed surveys were processed. The
      majority of respondents were geriatric psychiatrists (58%). Of the 20 different
      instruments that were listed on the survey, only six were selected as "routinely"
      or "often used" by the survey respondents. These instruments in declining order
      were: (1) the Folstein Mini-mental State Examination; (2) the Clock Drawing Test;
      (3) Delayed Word Recall; (4) the Verbal Fluency Test; (5) Similarities; and (6)
      the Trail Making Test. "Effectiveness" and "ease of administration" were the test
      characteristics most highly predictive of frequency of use. Open-ended comments
      highlighted patient factors that continue to provide challenges, including
      ethnicity/culture, language, education/literacy, and sensory impairment.
      Respondents concluded that "no single test is adequate." CONCLUSIONS:
      Psychogeriatricians worldwide routinely use a relatively small number of brief
      cognitive screening instruments. Further evaluation is necessary as the need
      increases for cognitive screening guidelines that inform public health
      initiatives related to dementia and neuropsychiatric syndromes.

PMID- 16466587
TI  - The attitude of elderly lay people towards the symptoms of dementia.
AB  - OBJECTIVES: To assess the attitude of elderly lay people towards the concept and
      symptoms of dementia. METHODS: A population-based, cross-sectional study of 859
      residents without dementia, aged 70 years or older, living in an urban area in
      Istanbul. Nine questions with yes/no responses were designed to investigate the
      attitudes of the responders to the concept of dementia and symptoms related to
      particular aspects of dementia. The chi(2)-test was used to test for differences
      between proportions of respondents in different age, sex and education groups.
      RESULTS: Dementia was considered as normal by the majority of respondents and age
      and education did not influence this attitude. Women were significantly less
      inclined to consider dementia and its associated problems as normal. CONCLUSION:
      The concept of dementia is generally not considered as a medical problem by the
      elderly Turkish population, independent of age and education. These results are
      important in guiding policy makers and shaping awareness raising campaigns of
      local Alzheimer's Associations.

PMID- 16466588
TI  - Association between cognitive function, behavioral syndromes and two-year
      clinical outcome in Chinese subjects with late-onset Alzheimer's disease.
AB  - OBJECTIVE: To examine associations between behavioral and psychological symptoms
      of dementia (BPSD), cognitive function and clinical deterioration over 2 years.
      METHODS: One hundred and four Chinese subjects with late-onset Alzheimer's
      Disease (AD) who presented to psychogeriatric clinics were followed for an
      average of 22.5 months. BPSD subgroups were categorized by latent class analysis
      using the Neuropsychiatric Inventory. Comprehensive cognitive profiles were
      performed with the Mattis Dementia Scale, the Hong Kong List Learning Test
      (HKLLT) and the Category Verbal Fluency Test. Interactions between cognitive
      function and behavioral syndromes were evaluated. Potential predictors for
      clinical deterioration were computed with logistic regression analysis. RESULTS:
      Three latent classes of subjects with similar behavioral syndromes were
      identified: Low BPSD (44%), Affective (32%) and Psychosis (24%) groups.
      Association between cognitive functions and BPSD was not significant. At follow
      up, a higher proportion of subjects in the Affective (70%) and Low BPSD (49%)
      groups remained stable at the same Clinical Dementia Rating. Baseline scores in
      the "recognition" test of the HKLLT and age were significant predictors for
      "deceased" status at 2-year follow-up. CONCLUSION: The lack of association
      between behavioral syndromes and cognitive function suggests that these
      relatively independent dimensions of dementia should be examined individually for
      different prognostic significance.

PMID- 16466589
TI  - Depression in mild cognitive impairment in a community sample of individuals 60
      64 years old.
AB  - OBJECTIVE: This cross-sectional study examined the prevalence and characteristics
      of depression in subjects with mild cognitive impairment (MCI). The data
      presented here are from the first wave of the longitudinal Personality and Total
      Health Through Life 60+ (PATH 60+) Project. METHOD: A total of 2551 community
      dwelling individuals in the age range 60-64 years were recruited randomly through
      the electoral roll. They were screened using a short cognitive battery and those
      who screened positive underwent detailed medical and neuropsychological
      assessments. There were 29 subjects who fulfilled the Mayo Clinic criteria for
      MCI and these were compared to 520 controls. Subjects were evaluated for
      depression symptoms and DSM-IV major and minor depression syndromes. RESULTS:
      Subjects with MCI had more minor depression and higher scores on a symptom scale.
      However, a multivariate examination of specific symptoms showed that the
      differences were confined to only two motivation-related symptoms ("felt slowed
      up" and "little interest or pleasure"). CONCLUSION: Motivation-related depressive
      symptoms are more relevant in subjects with MCI than mood-related symptoms.

PMID- 16466591
TI  - The Rowland Universal Dementia Assessment Scale (RUDAS) and the Folstein MMSE in
      a multicultural cohort of elderly persons.
AB  - OBJECTIVE: To compare the accuracy of the Rowland Universal Dementia Assessment
      Scale (RUDAS) and the Folstein Mini-mental State Examination (MMSE) for diagnosis
      of dementia in a multicultural cohort of elderly persons. METHODS: A total of 129
      community-dwelling persons were selected at random from a database of referrals
      to an aged-care team. Subjects were stratified according to language background
      and cognitive diagnosis, and matched for age and gender. The RUDAS and the MMSE
      were administered to each subject in random order. Within several days, a
      geriatrician assessed each subject for dementia (DSM-IV criteria) and disease
      severity (Clinical Dementia Rating Scale). All assessments were carried out
      independent and blind. The geriatrician also administered the Modified Barthel
      Index and the Lawton Instrumental Activities of Daily Living Scale, and screened
      all participants for non-cognitive disorders that might affect instrument scores.
      RESULTS: The area under the receiver operating characteristic curve (AUC) for the
      RUDAS [0.92, 95% confidence interval (95%CI) 0.85-0.96] was similar to the AUC
      for the MMSE (0.91, 95%CI 0.84-0.95). At the published cut-points (RUDAS < 23/30,
      MMSE < 25/30), the positive and negative likelihood ratios for the RUDAS were
      19.4 and 0.2, and for the MMSE 2.1 and 0.14, respectively. The MMSE, but not the
      RUDAS, scores were influenced by preferred language (p = 0.015), total years of
      education (p = 0.016) and gender (p = 0.044). CONCLUSIONS: The RUDAS is at least
      as accurate as the MMSE, and does not appear to be influenced by language,
      education or gender. The high positive likelihood ratio for the RUDAS makes it
      particularly useful for ruling-in disease.

PMID- 16466592
TI  - Behavioral and psychological symptoms of dementia in an Indian population:
      comparison between Alzheimer's disease and vascular dementia.
AB  - BACKGROUND: Differential patterns of brain lesions in patients with Alzheimer's
      disease (AD) or vascular dementia (VaD) can result in differing clinical courses
      and presentations. METHOD: Thirty patients with AD were compared with 29 patients
      with VaD for differences in behavioral symptoms using the Behavioral Pathology in
      Alzheimer's Disease (BEHAV-AD) rating scale. RESULTS: Patients with AD had
      significantly more delusions, hallucinations, anxieties and phobias and caregiver
      distress than patients with VaD. CONCLUSIONS: Behavioral symptoms in both AD and
      VaD exhibit specific longitudinal patterns. An understanding of the pattern can
      aid the treating physician in giving appropriate advice to caregivers regarding
      the course of the illness and also help them in planning appropriate
      interventions.

PMID- 16466593
TI  - Characteristics and health status change over 6 months in people with moderately
      severe to severe Alzheimer's disease in the U.K.
AB  - BACKGROUND AND OBJECTIVES: Until recently, attention and treatment strategies
      have focused mainly on patients in the early phases of Alzheimer's disease (AD).
      The objectives of this study were to collect information on moderately severe and
      severe AD patients (Mini-mental State Examination score < 15) in terms of
      epidemiological, clinical and economic characteristics and disease change in the
      later stages of AD, and to compare this specific AD population over 6 months with
      those in the earlier stages. METHODS: This descriptive analysis recruited
      institutionalized patients and patients living within the community from the city
      of London and the South-East region of the U.K. Subgroup analyses at baseline and
      6 months were performed using the study population from the London and South-East
      Region Alzheimer's Disease (LASER-AD) Study. Data from a range of clinical
      scales, a quality of life (QOL) scale and a resource-utilization questionnaire
      were analyzed. RESULTS: People with moderately severe or severe AD are a
      heterogeneous group with varying QOL, cognitive and functional disabilities,
      neuropsychological symptoms and relatively low health care resource consumption.
      This patient group continued to decline but progression of the disease was
      observed only in some domains. CONCLUSION: Even at the later stages of AD,
      patients show varying rates of decline. Improved knowledge about the
      characteristics and progression of the disease reveals that moderately severe and
      severe patients cannot be regarded as beyond help and have the potential to
      experience varying and even high levels of QoL.

PMID- 16466594
TI  - Psychosocial effects of age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD) affects approximately 10% of
      persons aged 65-74 years and 30% of those aged 75 and older and is the major
      cause of blindness in old age. AMD is progressive and irreversible. AIM: To
      review the psychosocial effects of AMD. METHOD: OVID data bases (MEDLINE,
      psycINFO and CINAHL) from 1966 to 2004 were reviewed. RESULTS: AMD is associated
      with functional impairment, high rates of depression, anxiety and emotional
      distress and increased mortality. Risk factors for depression are not well
      defined, except for the degree of functional impairment and impending or actual
      loss of vision in the second eye. Behavioral and self-management programs may be
      effective in managing depression associated with AMD, but few studies have been
      performed, and none using drugs or multimodal therapy. CONCLUSION: AMD will
      become even more prevalent as the population ages. Identification of risk factors
      for psychological consequences and of effective interventions remain to be
      recognized.

PMID- 16466595
TI  - The clinical importance of neutralizing antibodies in relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Neutralizing antibodies (NAbs) develop in patients receiving
      interferon beta (IFN-beta) for multiple sclerosis (MS). Debate continues
      concerning the relevance of NAb development on treatment efficacy. OBJECTIVE: To
      determine the incidence and clinical importance of NAbs in patients with
      relapsing-remitting MS (RRMS). METHODS: A comprehensive literature review was
      conducted using PubMed (accessed from 1983 to June 2005), Cochrane MS Group
      trials register (accessed June 2005), MEDLINE (accessed 1983 to June 2005), and
      Toxnet (accessed June 2005) databases. NAb-induced changes in clinical efficacy
      and disease progression were evaluated according to the clinical guidelines
      established by the American Academy of Neurology. RESULTS: Currently, there is no
      standardized assay to comparatively assess NAbs among different treatments. NAbs
      develop independent of age, sex, disease duration and progression index at the
      onset of treatment. The occurrence of NAbs varies from 2-45% depending on the
      treatment initiated. NAb+ patients demonstrate accelerated disease progression as
      confirmed by an approximate 1-point increase in the Expanded Disability Status
      Scale score. The odds of relapse during a NAb+ period are between 1.51 and 1.58
      (p < 0.03) with the time to first relapse being shortened by an average of 244
      days after 12 months of IFN-beta therapy. NAb+ patients experience an
      approximately four-fold increase (p = 0.009) in the median number of active T2
      magnetic resonance imaging (MRI) lesions compared to NAb-negative patients (1.4
      vs. 0.3 respectively, p < 0.01). CONCLUSION: The induction of NAbs in IFN-beta
      treated patients reduce clinical effect and accelerate disease progression.

PMID- 16466596
TI  - Clinical experience and management considerations with long-acting risperidone.
AB  - BACKGROUND: Risperidone is the first atypical anti-psychotic available in a long
      acting injectable formulation. OBJECTIVE: To provide an overview of the initial
      clinical experience gained with long-acting risperidone during clinical trials
      and in general treatment, including specific case studies, as well as providing
      practical advice on how to initiate treatment with this new drug. METHODS:
      Studies published between January 2002 and June 2005 that evaluated the
      pharmacokinetics, efficacy and safety of long-acting risperidone for the
      treatment of schizophrenia were reviewed, as identified from literature searches
      using Medline and EMBASE. Although not peer-reviewed, abstracts and posters on
      long-acting risperidone presented at key psychiatry and schizophrenia congresses
      during this period were also reviewed where available in the public domain.
      RESULTS: Clinical studies have consistently demonstrated that long-acting
      risperidone, available in dosage strengths of 25, 37.5 or 50 mg, given once every
      2 weeks, is both effective and well tolerated in patients with schizophrenia.
      Furthermore, significant and sustained clinical improvement has been reported in
      patients switched to long-acting risperidone from other oral and long-acting
      antipsychotic agents. Several patients groups, including the young, the elderly
      and patients with schizoaffective disorder, have also been shown to derive
      significant benefit from long-acting risperidone. CONCLUSION: A wide variety of
      patient groups may benefit from treatment with long-acting risperidone, including
      patients with suboptimal efficacy, particularly as a result of partial
      compliance, patients experiencing side-effects with another antipsychotic agent
      or those with a first episode of schizophrenia. Furthermore, long-acting
      risperidone, with its assured medication delivery, should improve patient
      compliance and assist patients in achieving remission, an important step towards
      functional recovery.

PMID- 16466598
TI  - The landscape after PEACE: do all ACE inhibitors act in an identical way?
AB  - The results of the Prevention of Events with Angiotensin Converting Enzyme
      Inhibition (PEACE trial), involving patients with stable coronary heart disease,
      demonstrated that the angiotensin-converting enzyme (ACE) inhibitor trandolapril
      did not reduce cardiovascular mortality, or the incidence of fatal or non-fatal
      myocardial infarction. These results were in conflict with the vast majority of
      previously published large-scale trials, and could be seen to weaken confidence
      in ACE inhibitor therapy of ischaemic heart disease. This review article examines
      the results of PEACE in comparison with the other major trials in terms of the
      severity of the disease in the patients, the statistical power of the analyses,
      the doses of the agents used and the concept of a 'class effect' of the ACE
      inhibitors.

PMID- 16466597
TI  - The effect of mirtazapine in patients with chronic pain and concomitant
      depression.
AB  - OBJECTIVE: To evaluate the safety, tolerability and efficacy of mirtazapine in
      patients with the primary diagnosis of chronic pain and concomitant depression in
      an open post-marketing surveillance study. RESEARCH DESIGN AND METHODS: 594
      patients with a primary diagnosis of at least one chronic pain syndrome (minimum
      duration of 3 months) and the diagnosis of concomitant depression, appropriately
      made by a neurologist or psychiatrist, were recruited at psychiatric and/or
      neurological outpatient facilities throughout Germany. The primary efficacy
      parameter was pain at baseline and endpoint using a patient self-assessment
      scale. Secondary analyses were performed at baseline, week 1 (day 7 +/- 2), week
      4 (day 28 +/- 4) and at endpoint (day 42 +/- 4 or early termination) and included
      safety and tolerability assessments. Investigators rated the severity of
      different potential co-morbidities (including depression) with a four-step rating
      scale (not present, mild, moderate, severe). RESULTS: 594 patients were enrolled
      and treated with mirtazapine (mean daily dose of 34.5 +/- 10.4 mg at study
      endpoint). A statistically significant (p < 0.0001; one sample sign test)
      reduction of pain from baseline to endpoint was found for the overall population.
      The percentage of patients free of pain or with only moderate pain increased
      significantly, irrespective of patients' age or pain syndromes. Furthermore, we
      found a substantial improvement from baseline to endpoint regarding co
      morbidities such as sleep disturbance, irritability and exhaustion. The number of
      adverse events was low (<7%; n = 37), with fatigue (n = 13) and weight gain (n =
      11) occurring most frequently. No previously-unknown side effects occurred. One
      hundred and six patients (18%) discontinued mirtazapine during the study. The
      main reason was lack of efficacy (6%, n = 33), which may be a reflection of sub
      optimal response to the anti-depressant or analgesic effect of the drug, but no
      appropriate rating scale was used to clarify this question. Only a small number
      of patients stopped the drug due to adverse events (3%; n = 15). At study
      endpoint, the majority of physicians and patients rated the overall efficacy and
      tolerability of mirtazapine as good or very good. Most patients (80%) continued
      the therapy after 6 weeks. CONCLUSIONS: Despite the limitations of an open
      observational study, our findings suggest that mirtazapine is a safe and well
      tolerated drug for use in daily clinical practice. It still remains unclear
      whether the reduction of pain, the enhancement of the depressed mood or the
      combination of both effects led to these results. Nevertheless, our data point to
      a potential beneficial effect of mirtazapine in the treatment of patients with
      pain and concomitant depression. However, more systematic research, including
      placebo-controlled studies, and further empirical testing are necessary.

PMID- 16466599
TI  - A double blind, placebo controlled trial of inert cellulose powder for the relief
      of symptoms of hay fever in adults.
AB  - OBJECTIVE: An inert cellulose powder has been on sale in the UK since 1994 as a
      remedy for hay fever but no scientific trials have been conducted previously. It
      is applied to the inside of the nose where it forms a gelatinous coating. The
      principal aim was to determine if there is a significant difference in the amount
      and type of rescue medication required for adult hay fever sufferers to control
      their symptoms while using either the inert cellulose powder or a placebo. The
      second objective was to see whether the cellulose powder resulted in an
      improvement in symptom control. RESEARCH DESIGN: A double blind, placebo
      controlled study was conducted of 97 adult hay fever sufferers, over the grass
      pollen season of 2004. Participants (selectively recruited to be living within
      the catchment area of a 50-km radius from Worcester, UK) were assigned randomly
      to two groups (A, Active and B, Placebo) matched by age by decades and gender. Of
      those completing the trial, group A had 19 males and 28 females and group B had
      21 males and 29 females. There were no significant differences between the groups
      in age distributions, severity of symptoms over the last 2 years or in medication
      taken. They completed daily symptom diary score cards and were allowed to take
      any medications they wished in addition to the inert cellulose powder or placebo
      because medication use was taken as an outcome measure. Results were analysed in
      relation to pollen counts. RESULTS: Significant differences were found in the
      amounts of rescue medication taken by the active and placebo groups (p < 0.05).
      More people in the placebo group took rescue treatments than those in the active
      group. No significant differences were found (p < 0.01) between the active and
      placebo groups in Likert scores for any of the rhinitis nasal symptoms or in the
      total Likert symptom daily scores. No adverse events were reported during the
      study. CONCLUSIONS: The amount of rescue medication taken by the placebo group
      was significantly more than that taken by the active group both overall,
      considering all types of medication, and also in the individual cases of
      antihistamines, nasal sprays and eye drops. These results provide evidence that
      the inert cellulose powder reduces the need to take rescue medication for the
      symptoms of hay fever.

PMID- 16466600
TI  - The effect of carvedilol on mortality risk in heart failure patients with
      diabetes: results of a meta-analysis.
AB  - BACKGROUND: Although beta-blocker therapy has been shown to improve survival in
      patients with chronic heart failure, this class of drugs tends to be
      underutilized in diabetic patients due to concerns about adverse metabolic
      effects, especially on glycemic control. No randomized clinical trial has
      specifically evaluated the effect of beta-blocker therapy on mortality in
      diabetic patients with heart failure. Previous meta-analyses combining results of
      heart failure trials with pharmacologically diverse beta-blockers suggest that
      the survival benefit in diabetic patients may be diminished compared to benefits
      in non-diabetic patients. However, some trial results indicate that carvedilol,
      which blocks beta1-, beta2-, and alpha1-receptors and is a potent antioxidant,
      may produce at least comparable effects in both patient groups. OBJECTIVES: To
      evaluate the effect of carvedilol in patients with heart failure and diabetes,
      specifically to determine if the survival benefit of carvedilol demonstrated in
      heart failure trials was as great in the subgroups of patients with diabetes.
      METHODS: A meta-analysis was performed that included 5757 patients with heart
      failure, 25% of whom had diabetes, from seven large placebo-controlled randomized
      trials with carvedilol. All large (> 100 patients) placebo-controlled, randomized
      trials with carvedilol in heart failure were included. The endpoint of all-cause
      mortality was examined in the overall population, patients without diabetes, and
      patients with diabetes. The number of patients needed to treat (NNT) for 1 year
      to prevent one death associated with carvedilol use in diabetic versus non
      diabetic patients was also calculated. The log-rank test and the Cox proportional
      hazards regression were used to compare the event time distributions of
      carvedilol versus placebo with respect to the outcome of mortality. RESULTS:
      Similar survival benefits were seen with carvedilol use in diabetic and non
      diabetic patients (relative risk reductions of 28% [95% confidence interval (CI)
      3-46%; p = 0.03] and 37% [95% CI 22-48%; p < 0.001], respectively). There were no
      significant differences between the relative mortality risk reductions or the NNT
      with carvedilol use in diabetic versus non-diabetic patients. The NNT for 1 year
      to prevent one death was 23 for all patients, as well as for non-diabetic
      patients, and 25 for the diabetic group. CONCLUSIONS: This meta-analysis provides
      evidence that the same survival benefit may occur with carvedilol in heart
      failure patients with and without diabetes. The low NNT in the severe heart
      failure trial, COPERNICUS, and the diabetic subgroup in this meta-analysis
      suggests that severe heart failure patients and heart failure patients with
      diabetes may particularly derive benefit from therapy with carvedilol.

PMID- 16466601
TI  - Type 2 diabetes in children and adolescents--the next epidemic?
AB  - OBJECTIVE: To provide an overview of the incidence of type 2 diabetes in children
      and adolescents and provide direction for clinicians who care for children and
      adolescents. RESEARCH DESIGN AND METHOD: The data presented in this review were
      obtained from published literature and abstracts presented at scientific
      meetings. Clinical trials and review articles were identified using the search
      terms 'metabolic syndrome', 'type 2 diabetes mellitus', 'children', and
      'adolescents' in a MEDLINE search from 1995-2005. Additionally, the
      bibliographies of the identified articles were reviewed. RESULTS: Type 2 diabetes
      is rising rapidly in children and adolescents worldwide. Changing a child's
      living environment to include physical activity, and a well balanced, low fat,
      high fiber diet, are important for the maintenance of a desirable body weight and
      improving insulin sensitivity. Maintaining euglycemia with metformin,
      sulfonylureas, thiazolinediones, and insulin is recommended. Effective treatment
      of co-morbid problems such as hypertension and dyslipidemia can decrease the risk
      of cardiovascular complications. CONCLUSIONS: The prevalence of type 2 diabetes
      in children will continue to rise until effective measures are taken to prevent
      obesity in this age group. Ensuring that children have a well-balanced low fat,
      high fiber, diet, combined with physical activity, will promote weight loss or
      maintenance, improve insulin sensitivity, and decrease the risk of diabetes and
      cardiovascular disease. Pharmacologic therapy is recommended for children who are
      unable to achieve satisfactory glycemic control through physical activity and
      diet.

PMID- 16466602
TI  - An observational study examining the impact of capecitabine on warfarin
      antithrombotic activity and bleeding complications.
AB  - OBJECTIVE: The objectives of this study are to quantify the frequency of
      concomitant use of capecitabine and warfarin, and to quantify the rate of
      bleeding events and elevated international normalized ratio (INR) among
      concomitant users of warfarin and capecitabine. RESEARCH DESIGN AND METHODS: We
      conducted a retrospective population-based study within the Henry Ford Health
      System (Detroit, MI) and the Kaiser Permanente Medical Care Program of Northern
      California (Oakland, CA). The study population included patients prescribed
      concomitant capecitabine and warfarin from 1 April 1997 through 31 July 2002.
      Data from the medical records of concurrent users were extracted through 31
      August 2002. MAIN OUTCOME MEASURES: Concomitant use of capecitabine and warfarin,
      bleeding events, and INR laboratory results, collected from computerized
      databases and medical record review. RESULTS: Overall, 11% of capecitabine users
      also received warfarin (99 / 883). Among 17 patients who received warfarin for
      venous access device prophylaxis, one bleeding event occurred during concomitant
      capecitabine/warfarin use (rate = 35.7 bleeding events per 100 person-years, 95%
      confidence interval [CI] 0.9-198.9), and no events occurred during use of
      warfarin alone (95% CI 0.0-136.2) (p = 0.50). Among patients prescribed warfarin
      for indications other than port prophylaxis, no bleeding events occurred during
      concomitant use of capecitabine and warfarin (95% CI 0.0-34.6), and one event
      occurred during warfarin use alone (rate = 9.2 bleeding events per 100 person
      years, 95% CI 0.2-51.3) (p = 0.54). We found one INR elevation > 3.0 among
      concomitant capecitabine/warfarin users receiving warfarin for port prophylaxis
      (rate = 35.7 per 100 person-years) and no INR elevations > 3.0 during use of
      warfarin alone (p = 0.46). Among patients using warfarin for indications other
      than port prophylaxis, the rates of INR > 3.0 were 309.7 per 100 person-years
      (95% CI 213.2-434.9) during concomitant capecitabine/warfarin use and 193.5
      events per 100 person-years (95% CI 119.8-295.8) during use of warfarin alone (p
      = 0.09). CONCLUSIONS: The results of our study show a low prevalence of
      capecitabine and warfarin concomitant use. We did not find large differences in
      the rates of bleeding events and elevated INR in patients receiving concomitant
      capecitabine and warfarin when compared with use of warfarin alone. While these
      results do not imply a lack of biologic interaction, our findings indicate that
      patients appear to be appropriately managed in clinical practice.

PMID- 16466603
TI  - Functionality and acceptability of a new electronic insulin injection pen with a
      memory feature.
AB  - OBJECTIVE: The HumaPen Memoir (HPM) is a new reusable insulin injection pen. It
      possesses an electronic component so that 16 insulin doses are stored in the
      memory. This study's aim was to evaluate the functionality of the device (i.e.,
      ability to deliver a set dose of insulin), its impact on patient safety, and
      patient/healthcare professional (HCP) acceptance. RESEARCH DESIGN AND METHODS: In
      this 6-10-week (3 visit) multinational, multi-centre, open-label, single-arm
      outpatient study, participants with type 1 or type 2 diabetes were assigned to
      inject either their prandial or basal insulin dose using the HPM and instructed
      to record all complaints with the study pen or user manual. Investigators
      submitted a complaint form to the sponsor for each participant complaint, and for
      adverse events (AEs) potentially related to the study pen. Where a complaint was
      possibly related to a pen malfunction, the pen was returned to the sponsor for
      assessment. Participant/HCP acceptance of the HPM was evaluated using
      questionnaires. RESULTS: Of the 300 participants (mean age 52 [SD 15] years), 58%
      were male and 62% had type 2 diabetes. The mean duration of pre-study pen use was
      7 years. The average exposure to the HPM was 8.2 (SD 1.6) weeks. Overall, 314
      study pens were used (14 were replacements). Functional complaints were reported
      for 24 devices (7.6%), of which 8 (2.5%) were permanent electronic failures, and
      15 (4.8%) were user-related (1 pen not returned for assessment). None of these
      functional issues resulted in a serious AE. Non-functional complaints were
      reported for 33 devices (10.5%). There were no pen-related hypoglycemic episodes
      and 2 pen-related hyperglycemic episodes were reported. The majority of
      participants (81.4%) preferred the HPM over their pre-study pen. The new insulin
      pen was generally rated higher than the pre-study pen for pen features and tasks
      associated with everyday pen use. CONCLUSIONS: No major functional issue of the
      HPM resulting in a serious AE was reported in this study. Based on the study
      results this new insulin pen demonstrated a favorable benefit-risk profile.

PMID- 16466604
TI  - Moxifloxacin versus levofloxacin for treatment of acute rhinosinusitis: a
      retrospective database analysis of treatment duration, outcomes, and charges.
AB  - OBJECTIVE: Antibiotics are clinically indicated for acute bacterial
      rhinosinusitis, but they may be prescribed inappropriately. This retrospective
      study examined how labeled recommendations for duration of moxifloxacin and
      levofloxacin treatment of acute bacterial rhinosinusitis compare with real-world
      practice, and compared the failure and recurrence rates, and associated charges.
      METHODS AND MAIN OUTCOME MEASURES: The PharMetrics Patient-Centric claims
      database was searched over a 3-year period for episodes of acute rhinosinusitis
      treated within 5 days with moxifloxacin or levofloxacin. The duration of
      antibiotic treatment prescribed was compared with the labeled recommendation.
      Failure rates (a second antibiotic claim to treat acute rhinosinusitis within 30
      days of the first claim), recurrence rates (subsequent antibiotic claims to treat
      any rhinosinusitis more than 30 days after the original or second [in the case of
      failure] claim), and treatment charges from the perspective of the payer (health
      insurer) were also compared using multivariate analysis. RESULTS: The initial
      duration prescribed of moxifloxacin was shorter than for levofloxacin (-1.65
      days, p < 0.0001), reflecting the shorter labeled recommendation (10 days versus
      10-14 days). The durations of monotherapy (-2.06 days, p < 0.0001) and of all
      antibiotic treatment (-1.97 days, p < 0.0001) were also significantly shorter for
      episodes treated initially with moxifloxacin. The odds ratio for treatment
      failure (0.718; 95% confidence interval = 0.598-0.863; p = 0.0004) and the hazard
      ratio for recurrence (0.652; p = 0.0005) were both significantly lower for
      moxifloxacin than for levofloxacin, and resulted in lower total treatment charges
      (-$37.94 +/- 13.65; p = 0.0055). CONCLUSION: The shorter treatment durations seen
      for moxifloxacin in this database of real-world care reflect the label
      recommended duration for acute rhinosinusitis. Despite this shorter duration of
      therapy, moxifloxacin resulted in better outcomes than levofloxacin in terms of
      the risk of treatment failure and recurrence. In addition, the total charges were
      lower for patients treated with moxifloxacin.

PMID- 16466605
TI  - The effects of insulin glargine treatment and an educational programme on
      glycaemic control in type 2 diabetes patients in clinical practice.
AB  - OBJECTIVE: This retrospective analysis was performed to establish the effect of
      initiating insulin glargine (LANTUS; sanofi-aventis, Paris, France), a once-daily
      basal insulin analogue, in combination with an educational programme on glycaemic
      control and body weight in sub-optimally controlled patients with Type 2 diabetes
      in clinical practice. RESEARCH DESIGN AND METHODS: We undertook a retrospective
      review of the medical records of 46 patients (mean age 61.5 +/- 8.6 years) with
      Type 2 diabetes. These patients had previously been treated with oral
      antidiabetic agents (OADs; n = 18) or insulin only (n = 28) and had then received
      insulin glargine in combination with OADs or prandial insulin, for 30 months.
      Records of metabolic control and body weight data were analysed at 9 and 30
      months. Patients had taken part in a diabetes educational programme before
      initiation of insulin glargine and received continued physician consultations
      throughout. RESULTS: Following initiation of insulin glargine, patients showed a
      significant decrease in HbA1c from 8.14 +/- 1.7% to 7.18 +/- 0.9% at 30 months (p
      < 0.001). When the results were analysed by pre-treatment, patients pre-treated
      with OADs showed a reduction in HbA1c of 2.3% at 30 months (p < 0.001), while
      patients pre-treated with insulin only showed a decrease in HbA1c of 0.4% (p <
      0.005). There was no significant change in body weight. No unexpected adverse
      events or episodes of severe hypoglycaemia (blood glucose < 40 mg/dL [< 2.2
      mmol/L]) occurred. CONCLUSIONS: Insulin glargine in combination with educational
      support and close clinical supervision significantly improved metabolic control
      without significant weight change in patients with Type 2 diabetes in clinical
      practice over 30 months. Additional studies are required to establish if similar
      results can be obtained in a larger cohort of patients.

PMID- 16466606
TI  - The effect of simvastatin on triglyceride-rich lipoproteins in patients with type
      2 diabetic dyslipidemia: a SILHOUETTE trial sub-study.
AB  - OBJECTIVE: To determine if simvastatin effectively decreases the elevated levels
      of triglyceride (TG), TG-rich lipoproteins, and small, dense LDL particles, which
      are characteristic of diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: We
      conducted a prespecified analysis from a double-blind, placebo-controlled,
      randomized, 6-week crossover trial in patients with type 2 diabetes and low HDL-C
      (< 40 mg/dL). Each patient was randomized to 1 of 6 possible treatment arms; each
      patient received simvastatin 80 mg, simvastatin 40 mg, and placebo over 3
      periods. We used the validated vertical auto profile (VAP) method to directly
      assess TG-rich lipoproteins and LDL subclasses. We assessed the efficacy of
      simvastatin to improve the lipoprotein profile in adult men (71%) and women (29%)
      (n = 151) with stable type 2 diabetes (HbA1C < 9%), LDL-C > 100 mg/dL, HDL-C < 40
      mg/dL, and fasting TG level > 150 and < 700 mg/dL (median = 273 mg/dL). MAIN
      OUTCOME MEASURES: Percentage change from baseline in IDL and VLDL (TG-rich
      lipoproteins), LDL subclasses, and additional lipoproteins at the end of each 6
      week treatment interval; percentage of patients who reached NCEP ATP III non-HDL
      goal of < 130 mg/dL by the end of each 6-week period. RESULTS: Both simvastatin
      80 mg and 40 mg significantly reduced VLDL-C, VLDL3, and IDL, as well as the four
      LDL subclasses measured with VAP, compared with placebo. Simvastatin 80 mg,
      compared with simvastatin 40 mg, provided additional efficacy. With simvastatin
      80 mg, 77.2% of patients not at their non-HDL-C goal of < 130 mg/dL at study
      baseline reached goal, compared with 65.7% following simvastatin 40 mg treatment,
      and 2.2% following placebo. CONCLUSIONS: Treatment with simvastatin effectively
      reduced the elevated levels of TG-rich lipoproteins and improved LDL composition
      in patients with type 2 diabetes. A large percentage of these patients attained
      the NCEP ATP III non-HDL-C goal of < 130 mg/dL, which demonstrates the
      improvement of the atherogenic profile in these patients.

PMID- 16466607
TI  - Cost-utility of somatropin (rDNA origin) in the treatment of growth hormone
      deficiency in children.
AB  - OBJECTIVE: The objective of this study was to generate estimates of cost
      effectiveness/utility of somatropin (rDNA origin) in the treatment of growth
      hormone deficiency (GHD) in children. METHODS: A decision-analytic model of the
      epidemiology and treatment of GHD in children was developed. Treatment of GHD was
      assessed in two hypothetical cohorts compared to no treatment--treatment with
      somatropin 0.030 mg/kg/day from ages 5 to 16 years, and treatment from ages 3 to
      18 years. Costs (stated in 2005 US$) included those related to drug acquisition,
      endocrinologist consultations, and primary care office visits. Estimates of
      patient weight by age and sex were derived from published literature, as was the
      proportion of patients achieving normal height through somatropin treatment and
      pre/post-treatment patient utilities. Cost-effectiveness/utility was estimated
      over patients' expected lifetimes, and was stated alternatively as discounted (3%
      per annum) US dollars per normal height year (NHY) gained, and cost per quality
      adjusted life-year (QALY) gained. Multivariate sensitivity analyses were
      conducted to ensure robustness of the model. RESULTS: The cost-effectiveness and
      cost-utility of treating children from ages 5 to 16 years with somatropin was
      estimated at approximately $8,900 per NHY gained and $37,000 per QALY gained,
      respectively. Corresponding ratios pertaining to treatment of children from ages
      3 to 18 years were $9,300 per NHY gained and $42,600 per QALY gained. Findings
      were relatively insensitive to variation in most model parameters. CONCLUSIONS:
      For both age cohorts, the cost-effectiveness/utility of somatropin in the
      treatment of GHD compares favorably to well-accepted threshold values. The use of
      somatropin represents reasonable value for money for the treatment of GHD in
      children.

PMID- 16466608
TI  - Improving the global management of the neurogenic bladder patient: part I. The
      complexity of patients.
AB  - BACKGROUND: The management of urinary incontinence in patients with neurological
      disease is complex. Physicians face a multitude of challenges related to
      progression of the primary condition, the presence of a diversity of other
      related and unrelated symptoms, the safety, efficacy and tolerability issues
      associated with multiple therapies being required and the changing need for
      collaboration with other specialities. SCOPE: Current guidelines produced by the
      urological communities, as well as the disease-focused organizations, aim to
      standardize care in their specific group of patients. A passive approach to
      implementation, however, means that guidelines produced are all too frequently
      not readily available to, read by or followed by the wider audience. In addition,
      each speciality has its own guidelines and a different view of the primary focus
      of care in neurological patients, which may lead to variations in recommendations
      and, subsequently, in clinical practice. A review of current urological and
      disease specific guidelines was made to evaluate differences between the
      published guidance between the specialities and within urology itself.
      CONCLUSIONS: Although availability of effective therapies remains a cornerstone
      of neurogenic bladder treatment, consideration must also be given to the non
      pharmacological and surgical issues related to the global management of this
      population. Improved cross-speciality interactions and development of patient
      specific treatment and follow-up plans, which are in keeping with the current
      guidelines of each speciality involved, may serve to enhance physicians'
      understanding of the importance of effective urinary incontinence treatment as
      well as the overall management of the patient.

PMID- 16466609
TI  - Effectiveness of budesonide nebulising suspension compared to disodium
      cromoglycate in early childhood asthma.
AB  - OBJECTIVE: The optimal treatment for early childhood asthma remains
      controversial. Budesonide (BUD) has shown superiority over placebo in infants,
      and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this
      double-blind, randomised, parallel-group study was to compare the effectiveness
      of nebulised BUD and DSCG in asthmatic children aged < 36 months. RESEARCH DESIGN
      AND METHODS: 82 infants (mean age 18.0 months [range, 11.6-31.2 months]) with
      suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12
      months, with one or more exacerbations in the past 3 months) were treated for 3
      months with nebulised BUD (Pulmicort Respules) 0.5 mg/2 mL bid or DSCG 20 mg/2 mL
      tid. Follow-up was at 6 months. MAIN OUTCOME MEASURES AND RESULTS: Patients
      treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3
      months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up
      (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65%
      for BUD and DSCG, respectively (p = 0.014), and nights without cough were 89% and
      78%, respectively (p = 0.016). Side-effects were mild and of similar frequency in
      both groups. CONCLUSIONS: Inhaled nebulised BUD was well tolerated and more
      effective than nebulised DSCG in reducing the incidence of asthma exacerbations
      and days with symptoms. These beneficial effects of BUD were maintained
      throughout the 6-month follow-up.

PMID- 16466610
TI  - Efficacy and tolerability of twice-daily pregabalin for treating pain and related
      sleep interference in postherpetic neuralgia: a 13-week, randomized trial.
AB  - OBJECTIVE: This trial evaluated the efficacy and safety of pregabalin dosed twice
      daily (BID) for relief of neuro-pathic pain associated with postherpetic
      neuralgia (PHN). RESEARCH DESIGN AND METHODS: The 13-week, double-blind, placebo
      controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600
      mg/day BID) or placebo. MAIN OUTCOME MEASURES: Primary efficacy measure was
      endpoint mean pain score from daily pain diaries. Secondary efficacy measures
      included endpoint mean sleep-interference score from daily sleep diaries and
      Patient Global Impression of Change (PGIC). Safety evaluations included adverse
      events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and
      laboratory testing. RESULTS: Pregabalin provided significant, dose-proportional
      pain relief at endpoint: difference from placebo in mean pain score, 150 mg/day, 
      0.88, p = 0.0077; 300 mg/day, -1.07, p = 0.0016; 600 mg/day, -1.79, p = 0.0003.
      Weekly mean pain scores significantly improved as early as week 1. Sleep
      interference in all pregabalin groups was also significantly improved at
      endpoint, compared with placebo (p < 0.001), beginning at week 1 (p < 0.01). At
      study termination, patients in the 150 (p = 0.02) and 600 mg/day (p = 0.003)
      groups were more likely to report global improvement than were those in the
      placebo group. Most AEs were mild or moderate. Among pregabalin-treated patients,
      13.5% withdrew due to AEs, most commonly for dizziness (16 patients, 5.8%),
      somnolence (8, 2.9%), or ataxia (7, 2.5%). CONCLUSIONS: Pregabalin, dosed BID,
      reduced neuropathic pain associated with PHN and was well tolerated. It also
      reduced the extent to which pain interfered with sleep. Pregabalin's effects were
      seen as early as week 1 and were sustained throughout the 13-week study.

PMID- 16466611
TI  - Identification, diagnosis, and management of anemia in adult ambulatory patients
      treated by primary care physicians: evidence-based and consensus recommendations.
AB  - OBJECTIVE: Provide recommendations for the identification, diagnosis, and
      management of ambulatory patients with anemia. MATERIALS AND METHODS: The
      RAND/UCLA Appropriateness Method was used to develop the recommendations. A
      literature review of anemia prevalence (based on a search of PubMed for the
      period 1990 to 2003), etiology, and treatment outcomes was reviewed by a panel
      comprised of nine physicians (six primary care, three specialists) who then rated
      336 clinical scenarios and grouped them into three categories: 'appropriate',
      'uncertain', or 'inappropriate'. RESULTS: Performing a complete blood count on a
      yearly basis was rated 'appropriate' for patients with an underlying chronic
      condition, for men > or = 50 years old, and for all women with no chronic
      condition on an every-5-years basis. Specific recommendations were made for five
      anemia management options (observation, referral, empiric trial of iron,
      transfusion, and erythropoietic growth factors). Recommendations for observation
      alone were based on age, gender, and hemoglobin level. Immediate referral to a
      gastroenterologist or hematologist for a work-up was rated 'inappropriate' in all
      cases. An empiric trial of iron was rated 'inappropriate' for women over age 40
      and for all men. Recommendations on the use of erythropoietic growth factors were
      based on hemoglobin level and anemia symptoms ('appropriate' if Hb < 9.5 g/dL, or
      if Hb = 9.5-11.0 g/dL and anemia symptoms were present). Finally, recommendations
      about transfusion were based on the severity of anemia and the presence of
      cardiovascular disease ('appropriate' in patients > or = 70 years old and in
      those presenting with either symptoms of anemia or underlying cardiovascular
      disease). The recommendations did not address anemia related to nutritional
      deficiencies, cancer/chemotherapy, or chronic renal failure. CONCLUSION: Primary
      care physicians should obtain screening blood counts, perform diagnoses, and
      manage anemia in patient groups known to be at risk. These recommendations on the
      identification, diagnosis, and management of anemia represent an opportunity to
      improve outcomes in ambulatory patients with anemia.

PMID- 16466612
TI  - Ocular permeation and inhibition of retinal inflammation: an examination of data
      and expert opinion on the clinical utility of nepafenac.
AB  - BACKGROUND: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs)
      for inflammation in the anterior segment, and pain control after cataract
      surgery, is well established. However, their effectiveness in the posterior
      segment has not been as well studied. Nepafenac ophthalmic suspension, 0.1% is a
      new topical NSAID pro-drug that has been approved by the US Food and Drug
      Administration (FDA) for the treatment of pain and inflammation after cataract
      surgery. Preclinical data suggest nepafenac may also provide unique efficacy in
      the posterior segment. SCOPE: We searched the PubMed database from 1966 to 2005
      for various combinations of the search terms 'nepafenac', 'ophthalmic',
      'inflammation', 'anterior segment', and 'posterior segment'. We review here the
      three articles identified in the search, and also include findings from three
      recent clinical trials. RESULTS: Nepafenac's corneal permeability characteristics
      are superior to those of ketorolac tromethamine, diclofenac sodium, and bromfenac
      sodium. Nepafenac is hydrolyzed by intraocular tissues to amfenac, a potent
      cyclooxygenase inhibitor. In addition to a limited hydrolysis in the cornea,
      significant bioactivation occurs in the iris/ciliary body and retina/choroid.
      Nepafenac administration significantly suppresses PGE2 synthesis in the
      retina/choroid. Topical nepafenac administration also significantly inhibits
      prostaglandin (PG)-mediated blood-retinal barrier breakdown and concurrent
      protein extravasation into the vitreous. In these studies, topical ketorolac and
      diclofenac failed to inhibit these key markers of inflammation. Nepafenac's
      clinical effectiveness in the posterior segment may be explained by its superior
      corneal permeation, biodistribution, and bioactivation to amfenac by the target
      tissues (i.e., iris, ciliary body, retina, and choroid) known to generate PGs.
      CONCLUSIONS: Nepafenac's ability to inhibit PG synthesis in the retina/choroid
      following topical administration indicates the drug also targets suppression of
      PG synthesis in the posterior segment. Nepafenac may therefore have a clinical
      role in conditions that are caused by PG-mediated vascular leakage, such as
      anterior chamber inflammation and cystoid macular edema following cataract
      surgery.

PMID- 16466613
TI  - An overview of the prevalence of 25-hydroxy-vitamin D inadequacy amongst elderly
      patients with or without fragility fracture in the United Kingdom.
AB  - BACKGROUND: Many studies have investigated the prevalence of 25-hydroxy-vitamin D
      inadequacy throughout the world and found a high prevalence of 25-hydroxy-vitamin
      D inadequacy in older patients, particularly those with fragility fracture.
      SCOPE: To review the findings from vitamin D audits from six units across the UK
      and compare with previously published data from around the world. Results from
      four units have been previously published (Belfast, Glasgow, London and Medway)
      and this paper presents new data from Southampton and Carshalton, and further sub
      analysis of the data from Medway. FINDINGS: Three audits of patients attending
      metabolic bone clinics (Carshalton, Medway and Southampton) identified 954
      patients, of which overall 49% had a prior fragility fracture. Mean 25-hydroxy
      vitamin D levels ranged from 47.7 nmol/L to 62.4 nmol/L. Of these patients 72.9
      88.9% had a 25-hydroxy-vitamin D level < 80 nmol/L, 68.8-83.3% < 70 nmol/L and
      37.5-59.1% < 50 nmol/L. The mean age of patients ranged from 60.0 to 67.5 years.
      Sub-analysis of the data by fracture status revealed that patients with fracture
      had lower mean levels of 25-hydroxy-vitamin D compared with patients without
      fracture. This was statistically significant in the sub-analysis of the Medway
      data (45.3 nmol/L versus 49.9 nmol/L, p < 0.005). Three audits identified 330
      patients with fragility fracture. Audits from Glasgow and Belfast specifically
      identified patients with fragility fracture. A subgroup of patients with fracture
      aged over 50 years from the Medway audit was also included in this group. Mean
      levels of 25-hydroxy-vitamin D ranged from 40.0 nmol/L to 52.3 nmol/L. 83.7-96.4%
      of patients had a 25-hydroxy-vitamin D level < 80 nmol/L, 73.3-89.7% < 70 nmol/L
      and 55.8-73.2% < 50 nmol/L. The mean age of patients ranged from 65.3 to 68.6
      years. The audits carried out in Belfast and Medway were also divided by
      supplementation status. Mean 25-hydroxy-vitamin D levels were 48.1 nmol/L in
      Belfast and 40.5 nmol/L in Medway in the patients not receiving supplements and
      53.8 nmol/L and 59.9 nmol/L, respectively in the patients receiving supplements.
      The difference was statistically significant in the Medway audit (p < 0.0001),
      but not in the smaller Belfast audit (p = 0.216). As would be expected, the
      prevalence of 25-hydroxy-vitamin D inadequacy was higher in the patients not
      receiving supplements, for example at the 70 nmol/L threshold: 82.6% versus 67.1%
      in Belfast and 89.6% versus 72.7% in Medway. Three audits specifically identified
      694 patients with hip fracture (Belfast, Glasgow and London). Mean levels of 25
      hydroxy-vitamin D ranged from 24.7 nmol/L to 36.1 nmol/L. Of these patients 90.7
      99.0% had a 25-hydroxy-vitamin D level < 80 nmol/L, 88.4-98.0% < 70 nmol/L and
      81.6-92.7% < 50 nmol/L. The mean age of patients ranged from 73.4 to 80.5 years.
      CONCLUSION: Inadequate 25-hydroxy-vitamin D levels are extremely common in the
      elderly and particularly so in patients with fragility fracture - specifically in
      those with hip fracture. Although the differing audit specifications and assay
      techniques used make direct comparisons difficult, the data do provide a snapshot
      of 25-hydroxy-vitamin D status across the UK and are consistent with those
      previously observed elsewhere in Europe and the rest of the world.

PMID- 16466614
TI  - Evaluation of the safety and tolerability of prolonged-release nicotinic acid in
      a usual care setting: the NAUTILUS study.
AB  - OBJECTIVE: The main objective was to evaluate the safety and tolerability of
      prolonged-release nicotinic acid (niacin; Niaspan) in an usual care setting with
      patients receiving treatment for dyslipidaemia in Germany: the multiceNtre, open,
      uncontrolled sAfety and tolerability stUdy of a modified-release nicoTinic acId
      formuLation in sUbjects with dySlipidaemia and low HDL-cholesterol (NAUTILUS).
      RESEARCH DESIGN AND METHODS: This was a multicentre, open-label, 15-week study.
      Eligible patients had a diagnosis of dyslipidaemia with lipids inadequately
      controlled by 4 weeks of diet treatment. Additionally, patients had low HDL
      cholesterol (< 1.03 mmol/L [< 40 mg/dL]) in men and < 1.29 mmol/L [< 50 mg/dL] in
      women), and had triglycerides < 9.03 mmol/L (< 800 mg/dL). Exclusion criteria
      included uncontrolled diabetes (HbA(1C) > 9%), significant hepatic, vascular or
      renal disease. The target dose was 2000 mg once daily. MAIN OUTCOME MEASURES: The
      main objective was to evaluate the safety and tolerability of prolonged-release
      nicotinic acid [incidence of adverse events (AE) and serious AE] in the overall
      population (the safety population). Efficacy parameters (lipid parameters) were
      also measured in the intent-to-treat population. RESULTS: A total of 566 patients
      were recruited, mostly with metabolic syndrome (39.4%), mixed
      hypercholesterolaemia (31.6%), isolated low HDL-cholesterol and markedly elevated
      cardiovascular risk for other reasons (10.8%), and primary hypercholesterolaemia
      (8.8%), according to NCEP/ATP III guidelines. The target dose was achieved by 65%
      of patients. Flushing was the most common side-effect (42%), as expected, and
      9.7% withdrew for flushing. Other drug-related AEs occurred at low frequency
      (18.6%), and 8.7% withdrew for an AE other than flushing. Most AEs were mild or
      moderate in severity. Serious AEs considered possibly related to treatment
      occurred in three patients (0.5%); all resolved following treatment withdrawal.
      There was no hepatotoxicity or serious muscle AE. CONCLUSIONS: Prolonged-release
      nicotinic acid was well tolerated, and these results support its use in the
      management of patients at elevated cardiovascular risk due to low HDL
      cholesterol.

PMID- 16466615
TI  - A community assessment, open-label study of the safety, tolerability, and
      effectiveness of mixed amphetamine salts extended release in school-age children
      with ADHD.
AB  - OBJECTIVE: To assess the safety, tolerability, and effectiveness of mixed
      amphetamine salts extended release (MAS XR) in school-age children with attention
      deficit/hyperactivity disorder (ADHD) treated in a community practice setting.
      METHODS: Children aged 6-12 years (N = 2968) with DSM-IV-defined ADHD entered a 9
      week prospective, open-label, non-comparative study of MAS XR at 386 sites. For
      at least 2 weeks before enrollment, subjects with well-controlled ADHD received
      their consistent dose of previously prescribed psychostimulant. Subsequently,
      this regimen was converted to an equivalent once-daily dose of 10-, 20-, or 30-mg
      MAS XR, according to a conversion algorithm. Tolerability and safety were
      assessed based on reported treatment-emergent adverse events and observed changes
      in vital signs and body weight. Effectiveness was assessed using a parent
      completed Conners' Global Index Scale (CGIS-P) measured 8 and 12 h postdose and a
      clinician-scored Clinical Global Impressions-Improvement (CGI-I) scale after 1,
      3, and 7 weeks of treatment. The dose of study medication could be adjusted at
      weeks 1 and 3 to a maximum of 40 mg/day. Outcome analyses used an intent-to-treat
      methodology, with last observations carried forward. RESULTS: Statistically
      significant improvement in ADHD behavior 8 and 12 h postdose occurred during the
      first week of treatment and was maintained through study endpoint (p < 0.0001).
      Results of the investigator-rated CGI-I at weeks 1, 3, and 7 were consistent with
      the parent-rated CGIS-P results, indicating that MAS XR treatment significantly
      improved symptoms compared with the baseline stimulant regimen (p < 0.0001). The
      incidence of treatment-related adverse events was low, and most AEs were mild in
      intensity. CONCLUSION: MAS XR 10-40 mg is a safe and effective once-daily
      medication for treatment of children with ADHD in a community practice setting.
      ADHD symptoms may be further reduced by converting from current pharmacotherapy
      to an optimally titrated dose of MAS XR.

PMID- 16466619
TI  - Mechanisms of immune-mediated skin diseases: an overview.
AB  - The skin is a frequent site of pathological immune responses that can take place
      in the dermal and/or the epidermal compartments.These immunopathological
      reactions often occur towards innocuous antigens and may be the result of T cell
      dependent and/or autoantibody dependent mechanisms. Defective immune regulation
      is increasingly recognized as very relevant in many skin and systemic immune
      mediated disorders. In some instances (e.g., psoriasis and atopic dermatitis)
      genetic predisposition can affect also the capacity of keratinocytes to initiate
      or perpetuate inflammatory responses. A more precise understanding of the
      molecular and cellular mechanisms underlying each disorder may allow the
      identification of novel targets for more effective therapeutic strategies.

PMID- 16466620
TI  - Role of cellular immunity in the pathogenesis of autoimmune skin diseases.
AB  - The pathomechanism of most autoimmune skin diseases is still elusive; however,
      recent clinical and basic research is leading novel insights into the cellular
      and molecular biological underlying pathways. Several types of infectious skin
      diseases are infiltrated by significant number of gamma/delta T cells and similar
      observations have been made in selected immune-mediated skin conditions. In
      particular, a role for gamma/delta T cells has been suggested in discoid lupus
      erythematosus, contact dermatitis, herpetiformis dermatitis, necrotizing
      cutaneous vasculitis, and cutaneous lesions of systemic sclerosis. The
      pathogenesis of these diseases is different and this may suggest multiple
      potential functions of this subset of T cells in the immune system of the skin.
      Furthermore, most T cells infiltrating tissue and organs undergoing fibrosis have
      the potential to produce high levels of interleukin 4. This is particularly true
      for the CD8+ or CD4+ CD8+ double positive T-cell subsets. Furthermore, leukocyte
      recruitment is a key event in immunity and a better understanding of the signals
      involved in autoimmune diseases constitutes a valuable basis for the development
      of new strategies, which control leukocyte migration and function under
      pathological conditions.

PMID- 16466621
TI  - New insights into the autoantibody-mediated mechanisms of autoimmune bullous
      diseases and urticaria.
AB  - The skin is a common target of cellular and/or antibody mediated pathological
      immune responses. Pemphigoids, pemphigus vulgaris and dermatitis herpetiformis
      are bullous disease due to autoantibodies targeting specific proteins of the
      skin. The pemphigoid autoantigens are the BP180 and the BP230 antigens, two
      components of the epithelial basement membrane zone. Additional antigenic targets
      reported in a portion of patients are laminin 5, the alpha6 subunit of the
      hemidesmosomal integrin alpha6beta4 and a glycoprotein termed p200. The epidermal
      and mucosal epithelial cells detachment (acantholysis) characteristic of
      pemphigus vulgaris is induced by autoantibodies directed against the desmoglein 3
      and 1. The desmogleins are desmosomal cadherins, which play a major role in the
      cell-to-cell adhesion. Dermatitis herpetiformis is regarded as cutaneous
      phenotype of coeliac disease. A novel autoimmune hypothesis of coeliac disease
      links wheat gliadin and tissue transglutaminase (TG2) in the gut, which leads to
      T cell response and IgA autoantibody formation. In dermatitis herpetiformis skin
      the target for IgA deposition seems to be epidermal TG3. Urticaria is a complex
      syndrome caused by both immune and non-immune mechanisms. In a subsets of
      patients with chronic urticaria mast cell degranulation is induced by
      autoantibodies directed against the a-subunit of the high-affinity IgE receptor,
      and/or the IgE.

PMID- 16466622
TI  - Lupus erythematosus and the skin.
AB  - Cutaneous manifestations of patients with lupus erythematosus (LE) are very
      frequent, show a great variety and can occur at any stage of the disease. The
      most consistent environmental trigger factors so far recognized are exposure to
      ultraviolet light and certain drug classes known to be capable of inducing LE in
      otherwise healthy individuals. A classification system has been established
      including clinical, histologic, photobiologic, serologic, and immunogenetic
      findings to better define the different cutaneous subtypes of LE. During their
      clinical evolution, the cutaneous manifestations vary considerably, and,
      therefore, the diseases which should be considered in differential diagnosis are
      different, according to the stages of disease development. Furthermore, 25 years
      of experience worldwide have revealed that individuals whose disease presentation
      is dominated by subacute cutaneous LE skin lesions and the presence of
      circulating anti-Ro/SS-A antibodies represent a rather homogeneous immunogenetic
      subphenotype of LE that enjoys a good prognosis over time. Treatment should be
      individualized according to disease severity. The majority of patients with
      cutaneous manifestations of LE do not require systemic immuno-suppressive/
      immunomodulatory therapy and the advent of recombinant biologicals has given hope
      to the small percentage of patients that suffer from particularly severe skin
      disease activity.

PMID- 16466623
TI  - Localized and systemic forms of scleroderma in adults and children .
AB  - Systemic sclerosis (SSc) presents a great deal of variability in the extent and
      severity of skin and internal organ involvement. The diagnostic and prognostic
      significance of autoantibodies in SSc is undisputed and the patient's
      autoantibody profile represents a fundamental tool for clinicians. Scleroderma is
      a rare condition in children. Unlike adults, localized scleroderma is more
      frequent than the systemic sclerosis, nevertheless it represents a disabling
      condition. In both conditions, no validated outcome measures and proven effective
      treatment is available to date.Raynaud's phenomenon (RP) is one the most common
      and significant clinical symptoms of SSc and therefore in patients with RP a
      capillaroscopic analysis should be carried out as soon as possible. The actual
      and select advantage of the early nailfold videocapillaroscopic (NVC) analysis is
      to distinguish between the primary RP and the secondary RP and to allow the early
      detection of SSc.

PMID- 16466624
TI  - The antiphospholipid antibody syndrome: diagnosis, skin manifestations and
      current therapy.
AB  - Antiphospholipid antibody syndrome is characterized by venous and/or arterial
      thrombosis and/or pregnancy morbidity associated with antiphospholipid antibodies
      (aPL), such as anticardiolipin antibodies, anti beta 2 glycoprotein I antibodies
      and positive lupus anticoagulant test. This syndrome may potentially affects any
      organ system including the skin. Livedo reticularis is the most frequently
      observed cutaneous lesion; other lesions, by order of frequency, are ulcerations,
      digital gangrene, subungueal splinter hemorrhages, superficial venous thrombosis,
      thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous
      necrosis and primary anetoderma. Skin lesions are more frequently observed in the
      catastrophic antiphospholipid syndrome, characterized by widespread microvascular
      occlusions involving multiple organs simultaneously. Patients with
      antiphospholipid associated thrombosis should receive long-term oral
      anticoagulants. The intensity of anticoagulation should be guided according to
      the nature of the thrombotic event (venous vs. arterial thrombosis). Patients
      with aPL-associated pregnancy morbidity should be treated with aspirin plus
      heparin and closely monitored during pregnancy. The treatment of the catastrophic
      antiphospholipid syndrome remains unsatisfactory. High dose intravenous steroids
      and parenteral anticoagulation should be supplemented by intravenous
      gammaglobulin and repeated plasma exchanges using fresh frozen plasma early on in
      the course of the syndrome.

PMID- 16466626
TI  - Skin manifestations in vasculitis and erythema nodosum.
AB  - Cutaneous lesions are frequent in medium-sized and small vessel systemic
      vasculitides. The classic cutaneous manifestation of vasculitis is palpable
      purpura; however the clinical manifestations greatly depend on the size of the
      vessels affected. They usually do not affect prognosis but relapsing or
      intractable forms have been described. When skin manifestations are only one of
      the clinical signs of vasculitis, treatment with corticosteroids and, when
      indicated, an immunosuppressant, is mandatory, which usually leads to the rapid
      disappearance of cutaneous lesions. Conversely, when skin lesions are isolated,
      the diagnosis can be more challenging, but initial treatment may be less
      aggressive, e.g., dapsone or colchicine, reserving corticosteroids only for those
      patients in whom the former are ineffective. Erythema nodosum (EN) is the most
      frequent septal panniculitis. In general it is characterized by the sudden
      eruption of one or more erythematous and tender nodules or plaques located mainly
      over the extensor sides of lower extremities. EN resolves with complete
      "restitutio ad integrum" of the skin in 3-6 weeks. Relapses are uncommon but in
      patients with idiophatic, streptococcal or EN associated with other upper
      respiratory tract infections they are more frequent. The main treatment of EN is
      that of the underlying associated conditions, if demonstrated. Aspirin and other
      NSAIDs in full doses are often sufficient.

PMID- 16466625
TI  - Skin involvement and outcome measures in systemic autoimmune diseases.
AB  - This paper focuses on skin manifestations that can be observed in autoimmune
      diseases such as rheumatoid arthritis (RA), Sjogren syndrome (SS),
      dermatomyositis (DM) and Behcet syndrome (BS). In RA the most widely recognized
      skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be
      observed either non-specific or related to the disease itself and/or to the
      commonly used drugs. Cutaneous manifestations are considered one of the most
      typical extraglandular features of primary SS, generally they are distinguished
      in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin
      dryness (xerosis) has been shown to be very common in pSS while vasculitis
      lesions include typically flat and palpable purpura and urticarial vasculits. In
      DM the skin manifestations are also frequent and include a heliotrope rash (blue
      purple discoloration) on the upper eyelids with edema, a flat red rash on the
      face and upper trunk, and erythema of the knuckles with a raised violaceous scaly
      eruption (Gottron rash). The most frequent mucocutaneous finding in BS is
      aphthous stomatitis which can not usually be differentiated from idiopatic
      reccurrent aphthous stomatitis on clinical grounds. The most typical skin
      manifestations are nodular lesions, which are commonly seen in BS and may be due
      to panniculitis [erythema nodosum (EN)-like lesions] or superficial
      thrombophlebitis.

PMID- 16466627
TI  - New insight into immunosuppression and treatment of autoimmune diseases.
AB  - The achievements in photoimmunology over the last years have not only broadened
      our knowledge how ultraviolet (UV) light compromises the immune system but have
      also yielded important insights into general immunology and photobiology.
      Therefore, studies will not only increase our understanding how UV acts as a
      pathogen but will also support the development of new therapeutic strategies,
      e.g. suppressing (auto)immune reactions via administration of antigen-specific
      regulatory T cells. Major advances in biotechnology have already resulted in the
      development of several novel agents for the treatment of inflammatory and
      autoimmune diseases. Some of these new immunomodulating drugs, such as
      mycophenolate mofetile and rituximab, are actually evaluated in controlled
      clinical trials to confirm the efficacy and safety profile in patients with
      autoimmune diseases. However, there is urgent need for specific
      immunointervention and further therapeutic options, especially for patients with
      autoimmune diseases in life-threatening situations and for non-responders to
      standard immunosuppression.

PMID- 16466628
TI  - Role of soluble and cell surface molecules in the pathogenesis of autoimmune skin
      diseases.
AB  - The skin is one of the most commonly involved tissue in rheumatic autoimmune
      diseases. Different mechanisms are thought to be implicated in the pathogenesis
      of skin lesions. In genetically predisposed individuals, ultraviolet (UV) light
      can contribute to the induction of skin lesions via an inflammatory process. UV
      light promotes the release of cytokines by keratinocytes and the induction of
      adhesion molecules on the surface of epidermal cells initiating a cascade of
      inflammatory events and recruiting immunoinflammatory cells into the skin. In
      this review data regarding the expression of TNF-alpha in lesional skin tissue
      from subacute cutaneous lupus erythematosus patients and the role of interferons
      in the pathogenesis of skin manifestations of rheumatic autoimmune diseases are
      reported. In addition, an overview on the expression of cellular adhesion
      molecules in these diseases is provided.UV light can also induce apoptosis in
      keratinocytes. During this cell death several enzymes became activated. Among
      them, desoxyribonuclease (DNase) is an enzyme involved in degrading DNA during
      apoptosis. Data regarding the activity of DNAse in patients with cutaneous lupus
      erythematosus as a possible risk factor for the development of systemic disease
      are here reported.

PMID- 16466629
TI  - Psoriasis and psoriatic arthritis: immunological aspects and therapeutic
      guidelines.
AB  - Psoriasis is an inflammatory skin disease that affects 1-3% of the European
      population. Chronic plaque psoriasis, the commonest form of the condition -
      affecting the majority of patients - usually manifests as red, heavily scaled
      plaques on elbows, knees, scalp and lower back, but any skin surface may be
      affected. Psoriasis is associated with an inflammatory sero-negative arthritis,
      namely "psoriatic arthritis", in approximately 15%of patients with psoriasis and
      occurs more commonly in people with inflammatory bowel disease such as patients
      with Crohn's disease. Several studies have demonstrated the role of genetic
      predisposition, innate and adaptive immunity in the pathogenesis of psoriasis.
      There is considerable evidence that innate immunity and specifically a
      dysregulation of the innate immune response is central to the development of
      psoriasis. The role of TNFalpha is particularly intriguing. The evidence includes
      further observations that a variety of anti-TNF approaches such as monoclonal
      antibodies and fusion proteins of soluble TNF receptors are effective therapies
      both in psoriasis and psoriatic arthritis. In this review, in addition to
      pathogenetic aspects, some preliminary guidelines for the use of anti-TNFalpha
      therapy in patients with psoriasis and psoriatic arthritis will be discussed.

PMID- 16466630
TI  - Autoinflammatory syndromes.
AB  - The autoinflammatory disorders are a new and expanding classification of
      inflammatory diseases characterized by recurrent episodes of systemic
      inflammation in the absence of pathogens, autoantibodies or antigen specific T
      cells. These disorders are caused by primary dysfunction of the innate immune
      system, without evidence of adaptive immune dysregulation. Innate immune
      abnormalities include aberrant responses to pathogen associated molecular
      patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent
      neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines
      (IL-1beta, TNF-alpha) or their receptors. The autoinflammatory diseases comprise
      both hereditary (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency,
      MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated
      Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma
      gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis,
      CRMO) and multifactorial (Crohn's and Behcet's diseases) disorders. Mutations
      responsible for FMF, TRAPS, CAPS, PAPA are in proteins involved in modulation of
      inflammation and apoptosis.

PMID- 16466631
TI  - Carcinogenic role of tumor necrosis factor-alpha inducing protein of Helicobacter
      pylori in human stomach.
AB  - Helicobacter pylori is the definitive carcinogen for stomach cancer and is known
      to induce proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1(IL-1) in the stomach. Based on our findings that TNF
      alpha is an endogenous tumor promoter, we identified the TNFalpha inducing
      protein (Tipalpha) gene family, and confirmed Tipalpha and HP-MP1 as new
      carcinogenic proteins of H. pylori.Tipalpha protein is unique to H. pylori, and
      this paper shows the strong tumor promoting activity of Tipalpha gene family, in
      cooperation with Ras protein and its mechanisms of action in relation to NF
      kappaB activation, and discusses the carcinogenic role of Tipalpha in stomach
      cancer. Our recent finding showing that penicillin-binding proteins of other
      bacteria are weak homologues of Tipalpha is also discussed.

PMID- 16466632
TI  - An antiviral mechanism investigated with ribavirin as an RNA virus mutagen for
      foot-and-mouth disease virus.
AB  - To prove whether error catastrophe/lethal mutagenesis is the primary antiviral
      mechanism of action of ribavirin against foot-and-mouth disease virus (FMDV).
      Ribavirin passage experiments were performed and supernatants of Rp1 to Rp5 were
      harvested. Morphological alterations as well as the levels of viral RNAs,
      proteins, and infectious particles in the BHK-21 cells infected using the
      supernatants of Rp1 to Rp5 and control were measured by microscope, real-time RT
      PCR, western-blotting and plaque assays, respectively. The mutation frequency was
      measured by sequencing the complete P1- and 3D-encoding region of FMDV after a
      single round of virus infection from ribavirin-treated or untreated FMDV-infected
      cells. Ribavirin treatment for FMDV caused dramatically inhibition of
      multiplication in cell cultures. The levels of viral RNAs, proteins, and
      infectious particles in the BHK-21 cells infected were more greatly reduced along
      with the passage from Rp1 to Rp5, moreover, nucleocapsid protein could not be
      detected and no recovery of infectious virus in the supernatant or detection of
      intracellular viral RNA was observed at the Rp5-infected cells. A high mutation
      rate, giving rise to an 8-and 11-fold increase in mutagenesis and resulting in
      some amino acid substitutions, was found in viral RNA synthesized at a single
      round of virus infection in the presence of ribavirin of 1000 microM and caused a
      99.7% loss in viral infectivity in contrast with parallel untreated control
      virus. These results suggest that the antiviral molecular mechanism of ribavirin
      is based on the lethal mutagenesis/error catastrophe, that is, the ribavirin is
      not merely an antiviral reagent but also an effective mutagen.

PMID- 16466633
TI  - Papaya ringspot virus coat protein gene for antigen presentation in Escherichia
      coli.
AB  - The coat protein (CP) of Papaya ringspot virus (PRSV) was analyzed for
      presentation of the antigenic peptide of animal virus, Canine parvovirus (CPV),
      in Escherichia coli (E. coli). The 45 nucleotides fragment coding for the 15-aa
      peptide epitope of the CPV-VP2 protein was either inserted into the PRSV-cp gene
      at the 5', 3' ends, both 5' and 3' ends or substituted into the 3' end of the
      PRSV cp gene. Each of the chimeric PRSV cp genes was cloned into the pRSET B
      vector under the control of the T7 promoter and transformed into E. coli. The
      recombinant coat proteins expressed from different chimeric PRSV-cp genes were
      purified and intraperitoneally injected into mice. All of the recombinant coat
      proteins showed strong immunogenicity and stimulate mice immune response. The
      recombinant coat proteins containing the CPV epitope insertion at the C terminus
      and at both N and C termini elicited ten times higher specific antisera in
      immunized mice compared with the other two recombinant coat proteins which
      contain the CPV epitope insertion at the N terminus and substitution at the C
      terminus.

PMID- 16466635
TI  - Differentially expressed genes in hemocytes of Vibrio harveyi-challenged shrimp
      Penaeus monodon.
AB  - Differential Display PCR technique (DD-PCR) was used for the analysis of altered
      gene expression in hemocytes of Vibrio harveyi-infected Penaeus monodon. Forty
      four combinations of arbitrary and oligo(dT) primers were used to screen for
      differentially expressed genes. A total of 79 differentially expressed bands
      could be identified from 33 primer combinations. These included 48 bands (61%)
      whose expression level increased and 31 bands (39%) decreased after V. harveyi
      challenge. Subsequently, forty-eight differential display fragments were
      successfully reamplified and cloned. A total of 267 clones were randomly selected
      and sequenced. The sequence analysis showed that 85 (31%) out of 267 clones were
      matched with sequences in the GenBank database which represented 24 different
      genes with known functions. Among the known genes, glucose transporter 1,
      interferon-related developmental regulator 1, lysozyme, profilin, SERPINB3, were
      selected for further confirmation of their differentially expression patterns by
      real-time PCR. The results showed increasing in expression level of the selected
      genes in shrimp hemocytes after microbial challenge suggesting the involvement of
      such genes in bacterial response in shrimp. The anti-lipopolysaccharide factor
      type 3 (ALFPm3) gene, previously reported in P. monodon (Supungul et al., 2002)
      was found among the up-regulated genes but diversity due to amino acid changes
      was observed. Increase in ALFPm3 transcripts upon V. harveyi injection is in
      accordance with that found in the previous study.

PMID- 16466634
TI  - Cloning and expression of Mycobacterium bovis secreted protein MPB83 in
      Escherichia coli.
AB  - The gene encoding MPB83 from Mycobacterium bovis Vallee111 chromosomal DNA was
      amplified by using polymerase chain reaction (PCR) technique, and the PCR product
      was approximately 600bp DNA segment. Using TA cloning technique, the PCR product
      was cloned into pGEM-T vector and the cloning plasmid pGEM-T-83 was constructed
      successfully. pGEM-T-83 and pET28a(+) were digested by BamHI and EcoRI double
      enzymes. The purified MPB83 gene was subcloned into the expression vector
      pET28a(+), and the prokaryotic expression vector pET28a-83 was constructed.
      Plasmid containing pET28a-83 was transformed into competence Escherichia coli
      BL21 (DE3). The bacterium was induced by isopropyl-Beta-D-thiogalactopyranoside
      (IPTG) and its lysates were loaded directly onto sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE), approximately 26 kDa exogenous
      protein was observed on the SDS-PAGE. The protein was analyzed using Western
      blotting. The results indicated that the protein was of antigenic activity of
      M.bovis. The results were expected to lay foundation for further studies on the
      subunit vaccine and DNA vaccine of MPB83 gene in their prevention against bovine
      tuberculosis.

PMID- 16466636
TI  - Identification of sex-specific expression markers in the giant tiger shrimp
      (Penaeus monodon).
AB  - Bulked segregant analysis (BSA) and AFLP were used for isolation of genomic sex
      determination markers in Penaeus monodon. A total of 256 primer combinations were
      tested against 6-10 bulked genomic DNA of P. monodon. Five and one candidate
      female- and male-specific AFLP fragments were identified. Female-specific
      fragments were cloned and further characterized. SCAR markers derived from
      FE10M9520, FE10M10725.1, FE10M10725.2 and FE14M16340 provided the positive
      amplification product in both male and female P. monodon. Further analysis of
      these markers using SSCP and genome walk analysis indicated that they were not
      sex-linked. In addition, sex-specific (or differential) expression markers in
      ovaries and testes of P. monodon were analyzed by RAP-PCR (150 primer
      combinations). Twenty-one and fourteen RAP-PCR fragments
      specifically/differentially expressed in ovaries and testes of P. monodon were
      successfully cloned and sequenced. Expression patterns of 25 transcripts were
      tested against the first stranded cDNA of ovaries and testes of 3-month-old and
      broodstock-sized P. monodon (N=5 and N=7-10 for females and N=4 and N=5-7 for
      males, respectively). Five (FI-4, FI-44, FIII-4, FIII-39 and FIII-58) and two
      (M457-A01 and MII-51) derived RAP-PCR markers revealed female- and male-specific
      expression patterns in P. monodon. Surprisingly, MII-5 originally found in testes
      showed a higher expression level in ovaries than did testes of juvenile shrimps
      but a temporal female-specific pattern in P. monodon adults.

PMID- 16466637
TI  - Purifications and characterizations of a ferredoxin and its related 2
      oxoacid:ferredoxin oxidoreductase from the hyperthermophilic archaeon, Sulfolobus
      solfataricus P1.
AB  - The coenzyme A-acylating 2-oxoacid:ferredoxin oxidoreductase and ferredoxin (an
      effective electron acceptor) were purified from the hyperthermophilic archaeon,
      Sulfolobus solfataricus P1 (DSM1616). The purified ferredoxin is a monomeric
      protein with an apparent molecular mass of approximately 11 kDa by SDS-PAGE and
      of 11,180+/-50 Da by MALDI-TOF mass spectrometry. Ferredoxin was identified to be
      a dicluster, [3Fe-4S][4Fe-4S], type ferredoxin by spectrophotometric and EPR
      studies, and appeared to be zinc-containing based on the shared homology of its N
      terminal sequence with those of known zinc-containing ferredoxins. On the other
      hand, the purified 2-oxoacid: ferredoxin oxidoreductase was found to be a
      heterodimeric enzyme consisting of 69 kDa alpha and 34 kDa beta subunits by SDS
      PAGE and MALDI-TOF mass spectrometry. The purified enzyme showed a specific
      activity of 52.6 units/mg for the reduction of cytochrome c with 2-oxoglutarate
      as substrate at 55 degrees C, pH 7.0. Maximum activity was observed at 70 degrees
      C and the optimum pH for enzymatic activity was 7.0 -8.0. The enzyme displays
      broad substrate specificity toward 2-oxoacids, such as pyruvate, 2-oxobutyrate,
      and 2-oxoglutarate. Among the 2-oxoacids tested (pyruvate, 2-oxobutyrate, and 2
      oxoglutarate), 2-oxoglutarate was found to be the best substrate with Km and kcat
      values of 163 microM and 452 min(-1), respectively. These results provide useful
      information for structural studies on these two proteins and for studies on the
      mechanism of electron transfer between the two.

PMID- 16466638
TI  - Misfolding-assisted selection of stable protein variants using phage displays.
AB  - We describe a phage display strategy, based on the differential resistance of
      proteins to denaturant-induced unfolding, that can be used to select protein
      variants with improved conformational stability. To test the efficiency of this
      strategy, wild-type and two stable variants of alpha1-antitrypsin (alpha1AT) were
      fused to the gene III protein of M13 phage. These phages were incubated in
      unfolding solution containing denaturant (urea or guanidinium chloride), and then
      subjected to an unfavorable refolding procedure (dialysis at 37 degrees C). Once
      the alpha1AT moiety of the fusion protein had unfolded in the unfolding solution,
      in which the denaturant concentration was higher than the unfolding transition
      midpoint (Cm) of the alpha1AT variant, around 20% of the phage retained binding
      affinity to anti-alpha1AT antibody due to a low refolding efficiency. Moreover,
      this affinity reduced to less than 5% when 10 mg/mL skimmed milk (a misfolding
      promoting additive) was included during the unfolding/refolding procedure. In
      contrast, most binding affinity (>95%) remained if the alpha1AT variant was
      stable enough to resist unfolding. Because this selection procedure does not
      affect the infectivity of M13, the method is expected to be generally applicable
      to the high-throughput screening of stable protein variants, when activity-based
      screening is not possible.

PMID- 16466639
TI  - Molecular control of gene co-suppression in transgenic soybean via particle
      bombardment.
AB  - Molecular co-suppression phenomena are important to consider in transgene
      experiments. Embryogenic cells were obtained from immature cotyledons and
      engineered with two different gene constructs (pHV and pHVS) through particle
      bombardment. Both constructs contain a gene conferring resistance to hygromycin
      (hpt) as a selective marker and a modified glycinin (11S globulin) gene (V3-1) as
      a target. sGFP(S65T) as a reporter gene was, however, inserted into the flanking
      region of the V3-1 gene (pHVS). Fluorescence microscopic screening after the
      selection of hygromycin, identified clearly the expression of sGFP(S65T) in the
      transformed soybean embryos bombarded with the pHVS construct. Stable integration
      of the transgenes was confirmed by polymerase chain reaction (PCR) and Southern
      blot analysis. Seeds of transgenic plants obtained from the pHV construct
      frequently lacked an accumulation of endogenous glycinin, which is encoded by
      homologous genes to the target gene V3-1. Most of the transgenic plants
      expressing sGFP(S65T) showed highly accumulation of glycinin. The expression of
      sGFP(S65T) and V3-1 inherits into the next generations. sGFP(S65T) as a reporter
      gene may be useful to increase the transformation efficiency of transgenic
      soybean with avoiding gene co-suppression.

PMID- 16466640
TI  - Molecular cloning and characterization of a novel stem-specific gene from
      Camptotheca acuminata.
AB  - In higher plants, P450s participate in the biosynthesis of many important
      secondary metabolites. Here we reported for the first time the isolation of a new
      cytochrome P450 cDNA that expressed in a stem-specific manner from Camptotheca
      acuminata (designated as CaSS), a native medicinal plant species in China, using
      RACE-PCR. The full-length cDNA of CaSS was 1735 bp long containing a 1530 bp open
      reading frame (ORF) encoding a polypeptide of 509 amino acids. Bioinformatic
      analysis revealed that CASS contained a heme-binding domain PFGXGRRXCX and showed
      homology to other plant cytochrome P450 monooxygenases and hydroxylases. Southern
      blotting analysis revealed that there was only one copy of the CaSS present in
      the genome of Camptotheca acuminata. Northern blotting analysis revealed that
      CaSS expressed, in a tissuespecific manner, highly in stem and lowly in root,
      leaf and flower. Our study suggests that CaSS is likely to be involved in the
      phenylpropanoid pathway.

PMID- 16466641
TI  - Tat-mediated protein transduction of human brain pyridoxine-5-P oxidase into PC12
      cells.
AB  - Pyridoxine-5-P oxidase catalyses the terminal step in the biosynthesis of
      pyridoxal-5-P, the biologically active form of vitamin B6 which acts as an
      essential cofactor. Here, a human brain pyridoxine-5-P oxidase gene was fused
      with a gene fragment encoding the HIV-1 Tat protein transduction domain
      (RKKRRQRRR) in a bacterial expression vector to produce a genetic in-frame Tat
      pyridoxine-5-P oxidase fusion protein. Expressed and purified Tat-pyridoxine-5-P
      oxidase fusion protein transduced efficiently into PC12 cells in a time- and dose
      dependent manner when added exogenously to culture media. Once inside the cells,
      the transduced Tat-pyridoxine-5-P oxidase protein showed catalytic activity and
      was stable for 48 h. Moreover, the formation of pyridoxal-5-P was increased by
      adding exogenous Tat-pyridoxine-5-P oxidase to media pre-treated with the vitamin
      B6 precursor pyridoxine. In addition, the intracellular concentration of
      pyridoxal-5-P was markedly increased when Tat-pyridoxal kinase was transduced
      together with Tat-pyridoxine-5-P oxidase into cells.These results suggest that
      the transduction of Tat-pyridoxine-5-P oxidase fusion protein presents a means of
      regulating the level of pyridoxal-5-P and of replenishing this enzyme in various
      neurological disorders related to vitamin B6.

PMID- 16466642
TI  - Chemical characteristics and immuno-stimulating properties of biopolymers
      extracted from Acanthopanax sessiliflorus.
AB  - During our search for macrophage stimulating compounds from medicinal plants, we
      isolated biopolymers from Acanthopanax sessiliflorus. Isolated fraction AS-5
      showed maximum potential, and stimulated lysosonal enzymatic activity by 230% at
      300 microg/ml. The nitric oxide (NO) producing ability of AS-5 100 microg/ml was
      58 microM when treated with interferon-gamma and lipopolysaccharide 20 micro/ml.
      The lymphocyte proliferating effects of isolated biopolymer fractions were also
      investigated. Highest lymphoproliferative activity (a 2.8-fold enhancement
      compared to salines treated group was exhibited by AS-3 at 200 micro/ml followed
      by AS-5 and AS-6. The AS-3 fraction stimulated only T-lymphocytes and had little
      or no effect on B-lymphocyte proliferation. Partially methylated alditol acetates
      were prepared to elucidate the glycosyl linkage-compositions of the AS-3 and AS-5
      biopolymers, and were analyzed by GC-MS. The AS-3 and AS-5 biopolymer fractions
      were found to contain 2,3,4-tri-O-methyl-D-glucitol, 2,3,4-tri-O-methyl-D
      galacitol 3,4,6-tri-O-methyl-galacitol, 2-O-methyl-arabinitol and 2,4,6-tri-O
      methyl-D-glucitol, 2,3,6-tri-O-methyl-D-galacitol linkages, respectively.

PMID- 16466643
TI  - Dual effects of nitric oxide on the large conductance calcium-activated potassium
      channels of rat brain.
AB  - Previously, we have shown that nitric oxide (NO) directly activates the Maxi-K
      channels. In the present study, we have investigated whether NO has prolonged
      effects on the Maxi-K channels reconstituted in lipid bilayer. Application of S
      nitroso-N-acetyl-D, L-penicillamine (SNAP), a NO donor, induced an immediate
      increase of open probability (Po) of Maxi-K channel in a dose-dependent manner.
      When SNAP was removed from the cytosolic solution, the Po did not simply returned
      to, but irreversibly decreased to a level lower than that of the control Po. At
      0.2 mM, (Z)-[N-(3-Ammoniopropyl)-N-(n-propyl)amino] diazen-1-ium-1,2-diolate
      (PAPA-NO), another NO donor, produced a similar increase of Po and decrease of Po
      upon washout. The increasing effects of SNAP on Po were not blocked by either 50
      U/ml superoxide dismutase (SOD) or 2 mM Nethylmaleimide (NEM) pre-treatments.
      However, NEM appears to be ineffective when applied after SNAP. These results
      suggest that NO can modulate Maxi-K channel via direct interaction and chemical
      modification, such as Snitrosylation in the brain.

PMID- 16466644
TI  - Protein kinase B inhibits endostatin-induced apoptosis in HUVECs.
AB  - Endostatin is a tumor-derived angiogenesis inhibitor, and the endogenous 20 kDa
      carboxyl-terminal fragment of collagen XVIII. In addition to inhibiting
      angiogenesis,endostatin inhibits tumor growth and the induction of apoptosis in
      several endothelial cell types. However, the mechanisms that regulate endostatin
      induced apoptotic cell death are unclear. Here, we investigated apoptotic cell
      death and the underlying regulatory mechanisms elicited of endostatin in human
      umbilical vein endothelial cells (HUVECs). Endostatin was found to induce typical
      apoptotic features, such as, chromatin condensation and DNA fragmentation in
      these cells. Thus, as the phosphoinositide 3-OH kinase (PI3K)/protein kinase B
      (PKB) signaling pathway has been shown to prevent apoptosis in various cell
      types, we investigated whether this pathway could protect cells against
      endostatin induced apoptosis. It was found that the inhibition of PI3K/PKB
      significantly increased endostatin-induced apoptosis, and that endostatininduced
      cell death is physiologically linked to PKB-mediated cell survival through
      caspase-8.

PMID- 16466645
TI  - Functional characterization of Zn2(+)-sensitive GABA transporter expressed in
      primary cultures of astrocytes from rat cerebral cortex.
AB  - The extracellular levels of gamma-aminobutyric acid (GABA), the main inhibitory
      neurotransmitter in the mammalian cerebral cortex, are regulated by specific high
      affinity Na(+)/Cl(-) dependent transporters (GATs). GAT1 mainly expressed in
      cerebrocortical neurons is thought to play an important role for clearance of
      GABA in the extracellular fluid, whereas there is a little information available
      for pharmacological importance for astrocytic GABA transporters. In the present
      study, we therefore described the functional characterization of GABA transport
      in primary cultures of astrocytes from rat cerebral cortex and the identification
      of GABA transporter subtype(s). GABA transport was Na(+) and Cl(-) dependent and
      saturable with a Michaelis constant (K(t)) of 9.3+/-2.8 microM. Na(+)- and Cl(-)-
      activation kinetics revealed that the Na(+)-Cl(-)-to-GABA stoichiometry was 2:1:1
      and concentrations of Na(+) and Cl(-) necessary for half-maximal transport
      (K(0.5)(Na) and K(0.5)(Cl)) were 78+/-28 mM and 9.6+/-2.6 mM, respectively. Na(+)
      dependent GABA transport was competitively inhibited by various GABA transport
      inhibitors, especially GAT2- or GAT3-selective inhibitor. In addition, Zn(2+),
      which has been reported to be a potent inhibitor of GAT3, was found to have a
      significantly but partially inhibitory effect on the Na(+)-dependent GABA
      transport in a concentration-dependent manner. Furthermore, reverse transcription
      PCR and Western blot analyses revealed that GAT2 and GAT3 are expressed in
      primary cultures of astrocytes. These results clearly showed that zinc is a
      useful reagent for separating GAT3 activity from GAT1- and GAT2-activities in
      CNS. To our knowledge, the present study represents the first report on the
      inhibitory effect of zinc on the Na(+)-dependent GABA transport in rat
      cerebrocortical astrocytes.

PMID- 16466646
TI  - Altered glycosylation of alpha-dystroglycan in neurons of Fukuyama congenital
      muscular dystrophy brains.
AB  - To test the hypothesis that the disruption of fukutin protein produces the brain
      pathology through hypoglycosylation of alpha-dystroglycan (alpha-DG), we
      immunostained Fukuyama congenital muscular dystrophy (FCMD) brains with an
      antibody that recognizes the polysaccharide epitope of alpha-DG. Immunoreactivity
      of the glia-limitans along the cortical surface, as well as that of the glial
      endfeet around vessel walls, was preserved in the FCMD cerebrum. However,
      fragmentation of the immunostained glia-limitans was noted in association with
      parenchymal protrusion and gyral fusion. In the FCMD cerebellum, this
      fragmentation of alpha-DG labeling was limited to the area of micropolygyria, and
      immunostaining at the glia-limitans and vessel walls was comparable to that of
      the control brains, in structurally normal areas. In the hippocampus, neurons of
      the dentate gyrus and corpus ammonis were immunopositive for alpha-DG in control
      subjects, but this staining was markedly decreased in FCMD brains. In contrast,
      immunolabeling of blood vessels and the glia-limitans was preserved in this
      region. Fukutin antisera clearly labeled hippocampal neurons in control brains,
      while this labeling was decreased in FCMD brains. Thus, hypoglycosylation of
      alpha-DG was evident in neurons, but not in the glial cell population of FCMD
      brains. This suggests that the mechanism of alpha-DG glycosylation may differ
      between neurons and glial cells, and that a fukutin gene defect may result in
      functional disruption through hypoglycosylation of both neuronal and glial alpha
      DG.

PMID- 16466647
TI  - The anterior ethmoidal nerve is necessary for the initiation of the
      nasopharyngeal response in the rat.
AB  - Stimulation of the nasal passages with ammonia vapors can initiate a
      nasopharyngeal response that resembles the diving response. This response
      consists of a sympathetically mediated increase in peripheral vascular
      resistance, parasympathetically mediated bradycardia and an apnea. The current
      study investigated the role of the anterior ethmoidal nerve (AEN) in the
      nasopharyngeal response in the rat, as it is thought that the AEN provides the
      main sensory innervation of the nasal passages. When both AENs were intact, nasal
      stimulation caused significant bradycardia, hypertension, and apnea and produced
      Fos label ventrally within the ipsilateral medullary dorsal horn (MDH) and
      paratrigeminal nucleus just caudal to the obex. This labeling presumably
      represents activation of second-order trigeminal neurons. When only one AEN was
      intact, the nasopharyngeal response was slightly attenuated, and a similar
      pattern of Fos labeling was only seen in the trigeminal nucleus ipsilateral to
      the intact AEN. The trigeminal labeling contralateral to the intact AEN was
      significantly reduced. When both AENs were cut, the nasopharyngeal response to
      nasal stimulation consisted of only a slight apnea and an increase in arterial
      pressure; the resultant Fos labeling within the trigeminal nucleus was
      significantly reduced. Cutting both AENs but not stimulating the nasal passages
      also produced some Fos labeling within the trigeminal nucleus. These findings
      suggest that a single AEN can provide sufficient afferent input to initiate the
      cardiorespiratory changes consistent with the nasopharyngeal response. We
      conclude that the AEN provides a unique afferent contribution that is capable of
      producing the diving response.

PMID- 16466648
TI  - Immunofixation reveals an apparent alpha heavy chain caused by precipitation of
      fibrinogen with IgA antiserum.
AB  - BACKGROUND: Fibrinogen present in serum specimens can interfere with the
      interpretation of serum protein electrophoresis. We report here the unexpected
      precipitation of fibrinogen by an IgA antiserum used in immunofixation
      electrophoresis. METHODS: Immunofixation electrophoresis of plasma combined with
      ethanol precipitation, serial dilution of plasma, and fibrinogen adsorption of
      the antiserum were used to investigate the apparent immunoreactivity of a
      commercial source of IgA antiserum to fibrinogen. RESULTS: Fibrinogen
      immunoreactivity by IgA antiserum was observed at fibrinogen concentrations > or
      =0.93 g/l. Ethanol precipitation of plasma removed fibrinogen and prevented the
      immunofixation of the protein by the IgA antiserum. Adsorption of the IgA
      antiserum with human fibrinogen removed its ability to precipitate fibrinogen,
      demonstrating cross-reactivity between the IgA antiserum and fibrinogen.
      CONCLUSIONS: Commercial sources of antiserum used for immunofixation
      electrophoresis may contain antibodies with specificity towards proteins
      typically absent from serum such as fibrinogen and can produce clinically
      misleading results.

PMID- 16466649
TI  - A two-center international evaluation of the Immulite 2000 automated serum
      gastrin assay.
AB  - OBJECTIVES: To assess the performance of the Immulite 2000 serum gastrin assay.
      DESIGN AND METHODS: Two-center validation and comparison with two manual gastrin
      assays. RESULTS: Serum, serum separator, EDTA and heparin tube results differed
      <20%. Samples showed <20% degradation for <6 h at room temperature, 3-day
      refrigerated, and underwent 3 freeze-thaw cycles. Imprecision was <8% between 20
      and 824 ng/L (10-393 pmol/L). Spike recovery was 88.5-106%, and recovery on
      dilution was 62-135%. There were no interferences from gastrin 1-14,
      pentagastrin, and cholecystokinin (CCK) 1-33 and CCK 26-33. The fasting reference
      range was <100 ng/L (<48 pmol/L). Regression slopes to the manual assays were 0.9
      and 0.97, with comparable clinical performance. CONCLUSIONS: The Immulite 2000
      assay is precise, accurate, and fast and compares well with established gastrin
      assays.

PMID- 16466650
TI  - Modulation of nitric oxide pathways: therapeutic potential in asthma and chronic
      obstructive pulmonary disease.
AB  - Nitric oxide (NO) is present in the exhaled breath of humans and other mammalian
      species. It is generated in the lower airways by enzymes of the nitric oxide
      synthase (NOS) family, although nonenzymatic synthesis and consumptive processes
      may also influence levels of NO in exhaled breath. The biological properties of
      NO in the airways are multiple, complex, and bidirectional. Under physiological
      conditions, NO appears to play a homeostatic bronchoprotective role. However, its
      proinflammatory properties could also potentially cause tissue injury and
      contribute to airway dysfunction in disease states such as asthma and chronic
      obstructive pulmonary disease (COPD). This article will review the physiological
      and pathophysiological roles of NO in the airways, discuss the rationale for the
      use of drugs that modulate NO pathways--nitric oxide synthase inhibitors and NO
      donors--to treat inflammatory airway diseases, and attempt to predict the likely
      therapeutic benefit of such agents.

PMID- 16466651
TI  - Developmental regulation of nerve and receptor mediated contractions of mammalian
      urinary bladder smooth muscle.
AB  - The development of nerve-induced activation, receptor properties and cellular
      signalling was examined by comparing the urinary bladder of new-born (0-2 days)
      and adult mice. Tissue strips were isolated and the effects of different
      neuromuscular agents on force were investigated during electrical field
      stimulation. The nerve-induced contractions of the urinary bladders from new-born
      mice were less influenced by desensitisation with alpha, beta-methylene ATP and
      more sensitive to scopolamine compared with those of the adult bladder. There
      were no differences in alpha, beta-methylene ATP or ATP responsiveness between
      adult and new-born tissue, showing that the lower purinergic component of the
      nerve-induced responses in the new-born mice was due to properties of the
      transmitter release rather than to a change in receptor function. Dose-response
      curves for carbachol revealed a lower peak response in new-born bladders compared
      with adults. The phasic component of the cholinergic contractions was pronounced
      and initiated at low carbachol concentrations in the new-born tissue. The
      carbachol contractions of both new-born and adult urinary bladder tissue were
      inhibited by the Rho kinase inhibitor Y27632 and by the protein kinase G
      activator 8-Br-cGMP. However, the sustained phase of carbachol contraction was
      significantly less sensitive to Y27632 and 8-Br-cGMP in new-born tissue. These
      results suggest that the receptor mediated calcium sensitisation mechanism is
      less prominent in new-born compared with adult mice and that the contractions of
      new-born bladders are less influenced by the nitric oxide (NO)-cGMP inhibitory
      pathway.

PMID- 16466652
TI  - Functional inhibition of intestinal and uterine muscles by non-permeant
      triphenylethylene derivatives.
AB  - We have previously shown that the triphenylethylene antiestrogen tamoxifen
      reversibly inhibited spontaneous contractile activity in isolated duodenal
      muscle. Now, we have synthesized different quaternary ammonium salts of tamoxifen
      by changing the substituents on the nitrogen of the alkylaminoethoxy side-chain,
      to obtain plasma membrane impermeable compounds. Synthesized molecules were N
      desmethyl-tamoxifen-hydrochloride, ethylbromide-tamoxifen and butylbromide
      tamoxifen, which differed in the size of their ionic side-chain. All compounds
      rapidly and reversibly inhibited spontaneous and CaCl(2)-induced contractions in
      mouse duodenum and uterus. Dose-response analyses revealed a structure-activity
      relationship where the larger the side-chain the higher the inhibitory potency.
      Fourier analyses on triphenylethylene-relaxed duodenal tissues showed that
      harmonic components of contractile activity were readily recovered upon exposure
      to the L-type calcium channel agonist 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2
      (trifluoromethyl)phenyl]-pyridine-3-carboxilic acid methyl ester (BAY-K644).
      Likewise, BAY-K644 completely reversed triphenylethylene-induced effects on
      uterine tonic tension. Our experiments suggest that impermeant tamoxifen
      derivatives relax visceral smooth muscle through a membrane-mediated non-genomic
      mechanism that involves inhibition of L-type calcium channels.

PMID- 16466653
TI  - Cytoplasmic transduction peptide (CTP): new approach for the delivery of
      biomolecules into cytoplasm in vitro and in vivo.
AB  - The protein transduction domain (PTD) of HIV-1 TAT has been extensively
      documented with regard to its membrane transduction potential, as well as its
      efficient delivery of biomolecules in vivo. However, the majority of PTD and PTD
      conjugated molecules translocate to the nucleus rather than to the cytoplasm
      after transduction, due to the functional nuclear localization sequence (NLS).
      Here, we report a cytoplasmic transduction peptide (CTP), which was deliberately
      designed to ensure the efficient cytoplasmic delivery of the CTP-fused
      biomolecules. In comparison with PTD, CTP and its fusion partners exhibited a
      clear preference for cytoplasmic localization, and also markedly enhanced
      membrane transduction potential. Unlike the mechanism underlying PTD-mediated
      transduction, CTP-mediated transduction occurs independently of the lipid raft
      dependent macropinocytosis pathway. The CTP-conjugated Smac/DIABLO peptide (Smac
      CTP) was also shown to be much more efficient than Smac-PTD in the blockage of
      the antiapoptotic properties of XIAP, suggesting that cytoplasmic functional
      molecules can be more efficiently targeted by CTP-mediated delivery. In in vivo
      trafficking studies, CTP-fused beta-gal exhibited unique organ tropisms to the
      liver and lymph nodes when systemically injected into mice, whereas PTD-beta-gal
      exhibited no such tropisms. Taken together, our findings implicate CTP as a novel
      delivery peptide appropriate for (i) molecular targeting to cytoplasmic
      compartments in vitro, (ii) the development of class I-associated CTL vaccines,
      and (iii) special drug delivery in vivo, without causing any untoward effects on
      nuclear genetic material.

PMID- 16466654
TI  - Food webs: experts consuming families of experts.
AB  - Food webs of habitats as diverse as lakes or desert valleys are known to exhibit
      common "food-web patterns", but the detailed mechanisms generating these
      structures have remained unclear. By employing a stochastic, dynamical model, we
      show that many aspects of the structure of predatory food webs can be understood
      as the traces of an evolutionary history where newly evolving species avoid
      direct competition with their relatives. The tendency to avoid sharing natural
      enemies (apparent competition) with related species is considerably weaker. Thus,
      "experts consuming families of experts" can be identified as the main underlying
      food-web pattern. We report the results of a systematic, quantitative model
      validation showing that the model is surprisingly accurate.

PMID- 16466655
TI  - Effects of transdermal nicotine on attention in adult non-smokers with and
      without attentional deficits.
AB  - Extant evidence suggests a possibility of self-medication to account for greater
      prevalence of cigarette smoking among adults with ADHD as they tend to show
      improvements on affective and cognitive measures, particularly on measures of
      sustained attention following nicotine administration. The present study was
      conducted to evaluate whether adult non-smokers with low attentiveness might
      exhibit greater improvements on measures of sustained attention than those with
      higher attentiveness using neuropsychological tests that had previously shown
      sensitivity to ADHD. On the basis of their scores on attention scales used in the
      diagnosis of adult ADHD, 62 male non-smokers were divided into 2 groups of either
      low or high attentiveness and treated with either a placebo or 7 mg nicotine
      patch. After 6 h of patch application each participant completed the Wisconsin
      Card Sorting Test (WCST), classic Stroop task, and Conners' Continuous
      Performance Test (CPT), which were administered in a counterbalanced order and a
      double-blind manner. No significant drug or group differences were observed on
      the Stroop task. On the Conners' CPT participants in the low attention group
      treated with nicotine committed significantly fewer errors of commission, showed
      improved stimulus detectability and fewer perseverations than those in the low
      attention placebo group. On the WCST nicotine significantly impaired the ability
      of participants in the high attention group to learn effective strategies to
      complete the test with fewer trials. The results showed nicotine-induced
      improvement on some measures of sustained attention in the low attention group
      and some decrement in working memory in the high attention group, which suggests
      that nicotine tends to optimize rather than improve performance on cognitive
      tasks.

PMID- 16466657
TI  - Clinical and pathological prognostic factors in squamous cell carcinoma of the
      vulva.
AB  - OBJECTIVE: The objective of this study was the prognostic analysis of
      clinicopathologic variables related to primary tumor and to lymph node
      metastases. METHODS: We retrospectively analyzed 389 cases of squamous cell
      carcinoma of the vulva. The following variables were studied: patients' age,
      diameter and location of the tumor, clinical tumor characteristics, depth of
      invasion, grade, lymphovascular space involvement (LVSI) and lymph node status.
      In the subset of 110 node positive patients, we evaluated number of positive
      nodes, laterality, extension of node dissection, lymph node chains involved,
      presence of extracapsular spread and rate of lymph node replacement. All
      variables with P value < 0.2 by the univariate analysis were successively
      subjected to multivariate analysis (Cox proportional hazard model). RESULTS:
      Among all the tumor-related variables age, clinical tumor characteristics, LVSI
      and lymph node status were found to be statistically significant predictors of
      survival for the log-rank test. On the basis of multivariate analysis, the nodal
      status was the most significant independent prognostic factor (hazard rate [HR]:
      2.06; confidence interval [CI] 95%: 1.57-12.07) followed by LVSI (HR: 3.47;
      CI95%: 1.85-7.85). The independent prognostic factors among the variables
      relative to positive nodes were the percentage of nodal replacement (HR: 6.99;
      CI95%: 3.51-16.14) and the extracapsular spread (HR: 4.88; CI95%: 2.96-10.14).
      CONCLUSIONS: Lymph node status and nodal features, such as extracapsular spread
      and nodal replacement rate, were shown to be independent factors. These factors
      should be considered to identify high risk patients and in planning further
      adjuvant therapy.

PMID- 16466656
TI  - Structural and functional localization of airway effects from episodic exposure
      of infant monkeys to allergen and/or ozone.
AB  - Both allergen and ozone exposure increase asthma symptoms and airway
      responsiveness in children. Little is known about how these inhalants may
      differentially modify airway responsiveness in large proximal as compared to
      small distal airways. We evaluated whether bronchi and respiratory bronchioles
      from infant monkeys exposed episodically to allergen and/or ozone differentially
      develop intrinsic hyperresponsiveness to methacholine and whether eosinophils
      and/or pulmonary neuroendocrine cells play a role. Infant monkeys were exposed
      episodically for 5 months to: (1) filtered air, (2) aerosolized house dust mite
      allergen, (3) ozone 0.5 ppm, or (4) house dust mite allergen + ozone. Studying
      the function/structure relationship of the same lung slices, we evaluated
      methacholine airway responsiveness and histology of bronchi and respiratory
      bronchioles. In bronchi, intrinsic responsiveness was increased by allergen
      exposure, an effect reduced by bombesin antagonist. In respiratory bronchioles,
      intrinsic airway responsiveness was increased by allergen + ozone exposure.
      Eosinophils were increased by allergen and allergen + ozone exposure in bronchi
      and by allergen exposure in respiratory bronchioles. In both airways, exposure to
      allergen + ozone resulted in fewer tissue eosinophils than did allergen exposure
      alone. In bronchi, but not in respiratory bronchioles, the number of eosinophils
      and neuroendocrine cells correlated with airway responsiveness. We conclude that
      episodically exposing infant monkeys to house dust mite allergen with or without
      ozone increased intrinsic airway responsiveness to methacholine in bronchi
      differently than in respiratory bronchioles. In bronchi, eosinophils and
      neuroendocrine cells may play a role in the development of airway
      hyperresponsiveness.

PMID- 16466658
TI  - Estradiol benzoate for preventing pregnancy in mismated dogs.
AB  - We investigated the use of a single treatment of estradiol benzoate (E2B) to
      prevent pregnancy in mismated dogs, including effects of dose, side effects, and
      mechanism of action. We used 74 female beagles aged 1-10 year. A single treatment
      of E2B (0.025, 0.05, 0.10, or 0.20 mg/kg; 10 dogs/dose) given 2 days after mating
      (5 days after ovulation) resulted in pregnancy rates of 70, 50, 10, and 0%,
      respectively, whereas pregnancy rate was 100% in 5 untreated (control) dogs.
      There were no side effects in dogs given E2B, regardless of dose. To clarify the
      mechanism of prevention of pregnancy, we investigated embryonic descent in the
      uterine tube and embryonic degeneration after treatment with 0.025 or 0.20 mg/kg
      of E2B; treatment delayed embryonic descent in the uterine tube and increased the
      incidence of embryonic degeneration. In conclusion, a single treatment of 0.020
      mg/kg of E2B given 2 days after mating effectively and safely prevented pregnancy
      in dogs.

PMID- 16466659
TI  - Molecular cloning and characterization of chicken lipopolysaccharide-induced TNF
      alpha factor (LITAF).
AB  - The inflammatory response to parasites, bacteria, and viruses is mediated by
      multiple host factors. TNF-alpha is one of the most pleiotropic cytokines in
      mammals, but has yet to be identified in avian species. In the current study, we
      isolated a full-length cDNA encoding the chicken homologue of LPS-induced TNF
      alpha factor (LITAF), transcription factor, with an open reading frame of 148
      amino acids and a predicted molecular mass of 16.0kDa. Quantitative RT-PCR
      analysis showed that chicken LITAF mRNA was predominantly expressed in spleen and
      intestinal intraepithelial lymphocytes (IELs). LITAF mRNA levels were up
      regulated following in vitro stimulation of macrophages for 4 h with Escherichia
      coli or Salmonella typhimurium endotoxin, and 18-48 h after treatment with
      Eimeria acervulina, E. maxima, or E. tenella, three causative agents of avian
      coccidiosis. LITAF mRNA was up-regulated by more than 700-fold in IELs isolated
      from E. maxima-infected birds. Purified recombinant LITAF protein expressed in E.
      coli or COS7 cells exhibited cytotoxic activity against chicken tumor cell lines
      in vitro, presumably through autocrine activation of TNF-alpha or its chicken
      homologue. This supposition was strengthened by the fact that treatment of
      chicken macrophages with recombinant LITAF induced the expression of TL1A (TNFSF
      15), a member of the TNF ligand super family. We conclude that chicken LITAF may
      play an important role in the regulation of TNF-alpha gene expression during the
      course of coccidiosis or tumorigenesis.

PMID- 16466660
TI  - Heavy metal contamination of soil and vegetables in suburban areas of Varanasi,
      India.
AB  - Heavy metal contamination of soil resulting from wastewater irrigation is a cause
      of serious concern due to the potential health impacts of consuming contaminated
      produce. In this study an assessment is made of the impact of wastewater
      irrigation on heavy metal contamination of Beta vulgaris (palak); this is a
      highly nutritious leafy vegetable that is widely cultivated and consumed in urban
      India, particularly by the poor. A field study was conducted at three major sites
      that were irrigated by either treated or untreated wastewater in the suburban
      areas of Varanasi, India according to normal practice. Samples of irrigation
      water, soil, and the edible portion of the palak (Beta vulgaris L. var All green
      H1) were collected monthly during the summer and winter seasons and were analyzed
      for Cd, Cu, Zn, Pb, Cr, Mn, and Ni. Heavy metals in irrigation water were below
      the internationally recommended (WHO) maximum permissible limits set for
      agricultural use for all heavy metals except Cd at all the sites. Similarly, the
      mean heavy metal concentrations in soil were below the Indian standards for all
      heavy metals, but the maximum value of Cd recorded during January was higher than
      the standard. However, in the edible portion of B. vulgaris, the Cd concentration
      was higher than the permissible limits of the Indian standard during summer,
      whereas Pb and Ni concentrations were higher in both summer and winter seasons.
      Results of linear regression analysis computed to assess the relationship between
      individual heavy metal concentration in the vegetable samples and in soil showed
      that Zn in soil had a positive significant relationship with vegetable
      contamination during winter. Concentrations of Cd, Cu, and Mn in soil and plant
      showed significant positive relationships only during summer. Concentration of Cr
      and Pb during winter season and Zn and Ni during summer season showed significant
      negative relationships between soil and plant contamination. The study concludes
      that the use of treated and untreated wastewater for irrigation has increased the
      contamination of Cd, Pb, and Ni in edible portion of vegetables causing potential
      health risk in the long term from this practice. The study also points to the
      fact that adherence to standards for heavy metal contamination of soil and
      irrigation water does not ensure safe food.

PMID- 16466661
TI  - Refractory cutaneous leishmaniasis in an adolescent: initial manifestation of
      type 1 diabetes.

PMID- 16466662
TI  - Prevalence of Brucella antibodies in rural and suburban communities in three
      provinces of Turkey: need for improved diagnosis and prevention.
AB  - OBJECTIVE: To determine the seroprevalence of Brucella-specific antibodies in
      rural and suburban communities in different provinces of Anatolia. METHOD: Cross
      sectional seroepidemiological study on serum samples collected in communities in
      two relatively developed provinces in west Anatolia with an official low
      prevalence of brucellosis and in one province in southeast Anatolia with a high
      prevalence. RESULT: The seroprevalence of brucellosis in the two provinces in the
      west Anatolia appears to be high and ranged from 2.9 to 8.5% in Rose Bengal test
      and from 0 to 5.6% in Wright serum agglutination test at a titer equal or higher
      than 1:100. The seroprevalence in communities in the province in southeast
      Anatolia was lower and this might well be attributed to vaccination of livestock
      in the year preceding the survey. CONCLUSION: Adherence to traditional farming
      practices and lifestyle, and a preference for fresh dairy contribute to the high
      seroprevalence of brucellosis. Vaccination of livestock is of utmost importance
      and the consumption of fresh milk and dairy products prepared from unpasteurised
      milk should be halted. Better access to laboratory testing is needed for the
      confirmation and management of brucellosis.

PMID- 16466663
TI  - Diagnostic associations between pleural and pulmonary tuberculosis.
AB  - OBJECTIVE: To evaluate diagnostic differences and associations between pleural
      tuberculosis (PLTB), and pulmonary tuberculosis alone (PTB), as well as, pleural
      and pulmonary co-infection (PLPTB) and PTB. METHODS: Data from a 6-year,
      population-based study in Houston, Texas, were analyzed by logistic regression
      modeling. Study personnel interviewed 2226 tuberculosis cases for TB risk
      assessment and reviewed medical records. Mycobacterium tuberculosis isolates from
      available culture-positive patients underwent genotyping. RESULTS: Among the
      categories analyzed [PTB, n=2070; PLTB, n=95; and PLPTB, n=61], mortality within
      180 days of TB presentation was highest for PLPTB patients (HR=1.8, P=0.045),
      followed by PTB (HR=1.0, referent), and PLTB (HR=0.97, P=0.9), after adjustment
      for age and HIV. Multivariate analysis identified history of liver disease, MTB
      culture negativity, having symptoms for <60 days, chest pain, and age>64 years as
      independent risk factors for PLTB. Symptoms for <60 days and HIV seropositivity
      predicted PLPTB. Patients with PLTB were significantly less likely to be
      genotypically clustered than patients presenting with PTB and patients diagnosed
      with PLPTB were significantly more likely to be identified has part of a cluster
      than pulmonary TB patients. CONCLUSIONS: PLTB presented as a more acute infection
      with additional symptoms and fewer symptomatic days, while PLPTB presented as a
      more severe disease with higher mortality compared with PTB. Given the different
      manifestations seen in this study, the biological mechanisms by which the pleural
      space is involved for PLTB and PLPTB may be substantially different.

PMID- 16466664
TI  - Cross-cultural and social diversity of prevalence of postpartum depression and
      depressive symptoms.
AB  - BACKGROUND: The prevalence of postpartum depression (PPD) is currently considered
      to be 10-15%. Most studies were performed with a brief unidimensional instruments
      (mostly the Edinburgh Postnatal Depression Scale-EPDS) with focus on depression
      and not on other symptoms and disorders. Most cited studies were conducted in
      Western economically developed countries. METHODS: We reviewed the literature on
      prevalence of postpartum depression and depressive symptoms in a wide range of
      countries. RESULTS: 143 studies were identified reporting prevalence in 40
      countries. It is demonstrated that there is a wide range of reported prevalence
      of PPD ranging from almost 0% to almost 60%. In some countries like Singapore,
      Malta, Malaysia, Austria and Denmark there are very few reports of PPD or
      postpartum depressive symptoms, whereas in other countries (e.g. Brazil, Guyana,
      Costa Rica, Italy, Chile, South Africa, Taiwan and Korea) reported postpartum
      depressive symptoms are very prevalent. CONCLUSIONS: We believe that the widely
      cited mean prevalence of PPD-10-15% is not representative of the actual global
      prevalence and magnitude of the problem, due to the wide range of reports. The
      variability in reported PPD might be due to cross-cultural variables, reporting
      style, differences in perception of mental health and its stigma, differences in
      socio-economic environments (e.g. poverty, levels of social support or its
      perception, nutrition, stress), and biological vulnerability factors. The
      elucidation of the underlying processes of this variability as well as the
      diversity of postpartum normal versus abnormal expressions of symptoms may
      contribute to better understanding of the diversified ante, peri- and postpartum
      phenomena.

PMID- 16466665
TI  - Mapping the emergence of heart disease in a black, urban population in Africa:
      the Heart of Soweto Study.
AB  - BACKGROUND: There is increasing evidence that many populations in the developing
      world are in "epidemiologic transition" with the subsequent emergence of more
      "affluent" disease states. The "Heart of Soweto Study" will systematically
      investigate the emergence of heart disease (HD) in a large urban population in
      South Africa. METHODS: Part of the conurbation of Johannesburg, South Africa,
      Soweto is a predominantly Black African community of 1 million individuals.
      During an initial two year period, all individuals presenting to the local
      Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic
      and diagnostic coding data in those with pre-established HD will form an
      abbreviated clinical registry of >12,000 "prevalent" cases. Similarly, socio
      demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in
      newly diagnosed patients will form a more detailed clinical registry of >5000
      "incident" cases. Sub-studies of the relationship between HIV status and HD and
      the optimal management of chronic heart failure will also be performed. RESULTS:
      These data will provide a unique insight into the causes and consequences of a
      broad spectrum of HD-related conditions in a "developing world" community in
      epidemiologic transition. Initially documented population rates, in addition to
      detailed examinations of the underlying risk factors and causes of HD-related
      morbidity/mortality will provide an important platform for future stages of the
      study: a community-based, population screening program and culturally specific
      primary and secondary programs of care. CONCLUSION: There is an urgent need to
      systematically track the emergence of HD in the developing world. Initially
      involving more than 15,000 individuals, the unique Heart of Soweto Study has the
      potential to provide a wealth of information in this regard.

PMID- 16466666
TI  - Improved anti-oxidant activity of superoxide dismutase by direct chemical
      modification.
AB  - Chemically modified derivatives of superoxide dismutase (SOD), i.e., cationized
      (Cat-SOD) and mannosylated SOD (Man-SOD), were designed to improve an ability of
      SOD to suppress reactive oxygen species (ROS)-mediated injury in the alveolar
      epithelium. To evaluate their effectiveness, an in vitro model of paraquat
      poisoning was developed with primary cultured rabbit alveolar type II cells.
      Despite a 5.6-fold higher cellular association than native SOD, Man-SOD did not
      protect cell injury due to paraquat following evaluation by MTT assay. In
      contrast, Cat-SOD exhibited a 140-fold higher cellular association than native
      SOD and greatly suppressed paraquat-induced cell injury, as well as lipid
      peroxidation. Incubation with 300 U/ml Cat-SOD for 2 h increased intracellular
      SOD activity 5.3-fold. The increase in intracellular SOD activity was
      significantly inhibited in the presence of cytochalasin B, an endocytosis
      inhibitor. Internalization of Cat-SOD was also confirmed by confocal laser
      scanning fluorescein microscopy. In addition, the protective effect of Cat-SOD
      against paraquat-induced cell injury was completely abolished by the presence of
      cytochalasin B. In conclusion, this study demonstrated that cationization of SOD
      greatly enhances its intracellular delivery and, as a consequence, produces a
      significant protective effect against ROS-mediated injury of the alveolar
      epithelium.

PMID- 16466667
TI  - Selective targeting of pentoxifylline to hepatic stellate cells using a novel
      platinum-based linker technology.
AB  - Targeting of antifibrotic drugs to hepatic stellate cells (HSC) is a promising
      strategy to block fibrotic processes leading to liver cirrhosis. For this
      purpose, we utilized the neo-glycoprotein mannose-6-phosphate-albumin (M6PHSA)
      that accumulates efficiently in HSC during liver fibrosis. Pentoxifylline (PTX),
      an antifibrotic compound that inhibits HSC proliferation and activation in vitro,
      was conjugated to M6PHSA. We employed a new type of platinum-based linker, which
      conjugates PTX via coordination chemistry rather than via covalent linkage. When
      incubated in plasma or in the presence of thiol compounds, free PTX was released
      from PTX-M6PHSA at a sustained slow rate. PTX-M6PHSA displayed pharmacological
      activity in cultured HSC as evidenced by changes in cell morphology and reduction
      of collagen I production. PTX-M6PHSA and platinum coupled PTX did not induce
      platinum-related toxicity (Alamar Blue viability assay) or apoptosis (caspase
      activation and TUNEL staining). In vivo distribution studies in fibrotic rats
      demonstrated specific accumulation of the conjugate in nonparenchymal cells in
      the fibrotic liver. In conclusion, we have developed PTX-M6PHSA employing a novel
      type of platinum linker, which allows sustained delivery of the drug to HSC in
      the fibrotic liver.

PMID- 16466668
TI  - Phosphodiesterases and compartmentalized cAMP signalling in the heart.
AB  - A key feature of the cAMP/cAMP-dependent protein kinase (PKA) transduction system
      is the compartmentalisation of its signalling enzymes and effectors. Given the
      large diversity of PKA targets within cardiac cells a precisely regulated and
      confined activity of such signalling pathway is essential for specificity of
      response. This appears to be achieved through the generation of local pools of
      high cAMP and activation of PKA at discrete subcellular locations.
      Phosphodiesterases (PDEs) are the only route for degrading cAMP and are thus
      poised to regulate intracellular cAMP gradients. Their spatial confinement to
      discrete compartments and functional coupling to individual receptors provides an
      efficient way to control local [cAMP](i) in a stimulus-specific manner. A better
      understanding of the distinctive role that individual PDEs play in shaping the
      cAMP signal in heart cells may lead to the development of new strategies for
      selective pharmacologic manipulation of cAMP signalling in defined functional
      domains.

PMID- 16466669
TI  - Modelling the dynamic air-water-sediment coupled fluxes and occurrence of
      polychlorinated biphenyls in a high altitude lake.
AB  - The BIODEP model in terms of atmosphere-lake interactions was developed. The
      model was applied to an oligotrophic, dimictic high altitude lake (Lake Redo,
      Pyrenees) for a range of polychlorinated biphenyl (PCB) congeners. High altitude
      lakes, which receive their contaminant inputs uniquely from the atmosphere
      through long-range atmospheric transport, provide ideal controlled environments
      for the study of the interactions between atmospheric depositional and water
      column biogeochemical processes. The BIODEP model was able to predict dissolved
      water concentrations and PCB accumulation in the lake sediment within a factor of
      2. This shows that the BIODEP model captures the essential processes driving the
      sink of POPs in high altitude lakes and that POP occurrence in the lake is driven
      by direct atmospheric inputs with limited influence from the watershed. An
      important seasonal variability in water column concentrations is predicted which
      should have important implications in sampling strategies. Furthermore, it is
      shown that diffusive air-water exchange dominated the PCB dynamics in the lake,
      especially for the less chlorinated biphenyls.

PMID- 16466670
TI  - The relationship between prolactin response and clinical efficacy of risperidone
      in acute psychotic inpatients.
AB  - Hyperprolactinemia can be induced by dopamine D2 receptor-binding drugs such as
      antipsychotic drugs. The author investigated the relationship between changes in
      prolactin (PRL) and clinical efficacy of risperidone. In this study, 27 acute
      psychotic inpatients completed a 12-week trial of risperidone. At baseline and at
      2, 4, 8, and 12 weeks after beginning medication, the author measured PRL,
      assessed hyperprolactinemia-related symptoms, and administered the Brief
      Psychotic Rating Scale (BPRS). Risperidone treatment significantly elevated serum
      PRL level (range: 26.9 ng/ml-320.0 ng/ml). The increases of PRL in females were
      higher than males. The changes in serum PRL levels were not significantly
      correlated with the improvements in total BPRS scores. PRL-related symptoms such
      as irregular menstruation, galactorrhea, or erectile dysfunction occurred in nine
      subjects (7 females and 2 males) whose serum PRL levels increase very highly
      after 2 weeks of risperidone. In conclusion, our study suggests that the changes
      in serum PRL levels were not significantly correlated with clinical efficacy of
      risperidone.

PMID- 16466671
TI  - Misoprostol versus cervagem for the induction of labour to terminate pregnancy in
      the second and third trimester: a systematic review.
AB  - AIMS: to compare the benefits and harms of misoprostol to induce labour in the
      second and third trimester of pregnancy with cervagem. METHODS: MEDLINE was
      searched using the terms abortion, induced; abortifacient agents; pregnancy,
      second trimester; pregnancy, third trimester; misoprostol; cervagem; and
      gemeprost to identify randomised controlled trials in which misoprostol was
      compared with cervagem, for induction of labour to terminate pregnancy in the
      second or third trimester. Outcomes included vaginal birth not achieved within
      24h; induction to delivery interval; analgesia requirements; blood loss; blood
      transfusion; surgical evacuation of the uterus; maternal death or serious
      maternal morbidity; side effects. RESULTS: Six randomised trials were included.
      Five compared vaginal misoprostol with cervagem [el Refaey H, Hinshaw K,
      Templeton A. The abortifacient effect of misoprostol in the second trimester: a
      randomized comparison with gemeprost in patients pre-treated with mifepristone
      (RU486). Hum Reprod 1993;8(10):1744-6; Ho PC, Chan YF, Lau W. Misoprostol is as
      effective as gemeprost in termination of second trimester pregnancy when combined
      with mifepristone: a randomised comparative trial. Contraception 1996;53(5):281
      3; Nuutila M, Toivonen J, Ylikorkala O, Halmesmaki E. A comparison between two
      doses of intravaginal misoprostol and gemeprost for induction of second trimester
      abortion. Obstetr Gynecol 1997;90(6):896-900; Wong KS, Ngai CS, Wong AY, Tang LC,
      Ho PC. Vaginal misoprostol compared with vaginal gemeprost in termination of
      pregnancy: a randomized controlled trial. Contraception 1998;58(4):207-10;
      Dickinson JE, Godfrey M, Evans SF. Efficacy of intravaginal misoprostol in second
      trimester termination of pregnancy: a randomized controlled trial. J Mater Fetal
      Med 1999;7(3):115-9], and one oral misoprostol with gemeprost [Bartley J, Baird
      DT. A randomised study of misoprostol and gemeprost in combination with
      mifepristone for induction of abortion in the second trimester of pregnancy. Br J
      Obstetr Gynaecol 2002;109(11):1290-4]. Vaginal misoprostol compared with cervagem
      was associated with reduced narcotic analgesia (3 studies, 169 women, RR 0.64 95%
      CI 0.49-0.84), and surgical evacuation of the uterus (5 studies, 319 women, RR
      0.71 95% CI 0.53-0.95). No other statistically significant differences were
      observed for other outcomes with reported data. In the single trial comparing
      oral misoprostol with gemeprost, reported outcomes were similar. CONCLUSIONS:
      Vaginal misoprostol for the termination of second and third trimester of
      pregnancy appears as effective as cervagem, but information about maternal safety
      is limited.

PMID- 16466672
TI  - Thermodynamic properties of enzyme-catalyzed reactions involving guanine,
      xanthine, and their nucleosides and nucleotides.
AB  - The standard Gibbs energies of formation of species in the guanosine triphosphate
      and the xanthosine triphosphate series have been calculated on the basis of the
      convention that the standard Gibbs energy of formation for the neutral form of
      guanosine is equal to zero in aqueous solution at 298.15 K and zero ionic
      strength. This makes it possible to calculate apparent equilibrium constants for
      a number of enzyme-catalyzed reactions for which apparent equilibrium constants
      have not been measured or cannot be measured directly because they are too large.
      The eventual elimination of this convention is discussed. This adds ten reactants
      to the database BasicBiochemData3 that has 199 reactants. The standard
      transformed Gibbs energies of formation of these ten reactants are used to
      calculate apparent equilibrium constants at 298.15 K, 0.25 M ionic strength, and
      pHs 5, 6, 7, 8, and 9. The pKs, standard Gibbs energies of hydrolysis, and
      standard Gibbs energies of deamination are given for the reactants in the ATP,
      IMP, GTP, and XTP series.

PMID- 16466673
TI  - Design of carbohydrate multiarrays.
AB  - Recently, microarray technology has increasingly been widely applied in
      glycobiology. This technology has rather evident potential advantages: unlimited
      number of carbohydrate ligands coated onto one small sized chip, enormously low
      consumption of both carbohydrate ligands and carbohydrate-binding proteins to be
      tested, etc. Literature data demonstrate that three approaches are used for
      glycoarray design. The first one is based on the physical adsorption of
      glycomolecules on a surface (as in a common ELISA), the second one-on covalent
      immobilization, and the third one-on a streptavidin-biotin system. In all of the
      described methods, carbohydrate ligands were placed on chips as a 2D monolayer
      and high sensitivity was achieved due to fluorescent detection. Notably, a
      tendency of stepping from model chips toward real multiarrays, where the number
      of carbohydrate ligands can be up to two hundred, has been observed the last 2
      years, this already producing a number of interesting findings when studying
      carbohydrate-binding proteins. In 2005 new construction, 3D glycochip was
      described, where 150 mum diameter polyacrylamide gel elements serve as
      microreactors instead of 2D dots. As a result of the 3D placement of a ligand,
      two orders of magnitude increase of its density is possible, this providing
      principal signal improvement during fluorescent detection and increasing method
      sensitivity. At the same time, carbohydrate consumption is low, i.e.,
      approximately 1 pmol per gel element. Copolymerization chemistry enables the
      immobilization of several glycomolecule classes to the gel, in particular,
      aminospacered oligosaccharides, polyacrylamide conjugates, and even 2
      aminopyridine derivatives of oligosaccharides, which are widely used in the
      structural analysis of glycoprotein N-chains.

PMID- 16466674
TI  - Value of fat-suppressed PD-weighted TSE-sequences for detection of anterior and
      posterior cruciate ligament lesions--comparison to arthroscopy.
AB  - OBJECTIVE: To evaluate fat-suppressed (FS) proton-density-weighted (PDw) turbo
      spin-echo (TSE) magnetic resonance imaging for the detection of anterior and
      posterior cruciate ligament lesions in comparison to arthroscopy. MATERIALS AND
      METHODS: In a prospective study 31 knee joints were imaged on a 1.5T MR scanner
      (Vision, Siemens, Erlangen) prior to arthroscopy using following sequences: (a)
      sagittal FS-PDw/T2w TSE (TR/TE: 4009/15/105 ms); (b) sagittal PDw/T2w TSE
      (TR/TE:3800/15/105 ms). Further imaging parameters: slice thickness 3mm, FOV 160
      mm, matrix 256 x 256. A total of 62 anterior and posterior cruciate ligaments
      (ACL/PCL) were evaluated, standard of reference was arthroscopy. Sensitivity,
      specificity, positive (ppv) and negative predictive value (npv) and accuracy were
      calculated. RESULTS: Twenty-one cruciate ligament ruptures were detected in
      arthroscopy, 19 ACL- and 2 PCL-ruptures (on MRI 34/124, 25/62 ACL, 9/62 PCL
      lesions). For all four sequences in the 31 patients with arthroscopic correlation
      sensitivity, specificity, ppv, npv and accuracy were 86%, 98%, 95%, 93% and 94%
      for detection of tears, and 84%, 100%, 100%, 80% and 90% for ACL-ruptures
      respectively. The two PCL-ruptures were true positive in all sequences, one
      intact PCL was diagnosed as torn (false positive). CONCLUSIONS: Fat-suppressed
      PDw/T2w TSE-MR sequences are comparable to PDw TSE sequences for the detection of
      ACL/PCL-lesions.

PMID- 16466677
TI  - A Bayesian model for joint segmentation and registration.
AB  - A statistical model is presented that combines the registration of an atlas with
      the segmentation of magnetic resonance images. We use an Expectation Maximization
      based algorithm to find a solution within the model, which simultaneously
      estimates image artifacts, anatomical labelmaps, and a structure-dependent
      hierarchical mapping from the atlas to the image space. The algorithm produces
      segmentations for brain tissues as well as their substructures. We demonstrate
      the approach on a set of 22 magnetic resonance images. On this set of images, the
      new approach performs significantly better than similar methods which
      sequentially apply registration and segmentation.

PMID- 16466676
TI  - Reference values for the 6-min walk test in healthy subjects 20-50 years old.
AB  - In 102 healthy Caucasians, 20-50 years old, we investigated the effect of
      anthropometrics on the 6-min walk test (6MWT), in order to provide reference
      values for walk distance (6MWD), oxygen saturation (SpO2), pulse rate (PR),
      respiratory rate (RR), breathlessness perception (VAS) and for the walking
      distance and body weight product (DW). The mean 6MWD and DW values were 593 +/-
      57 and 638+/-44 m (P < 0.01) and 35,030 +/- 5306 and 48,882 +/- 6555 kg m (P <
      0.01), respectively for women and for men. While walking, SpO2 remained unaltered
      and subjects reached 67 +/- 10% of their maximal predicted heart rate and a RR
      mean value of 19 +/- 4 bpm. VAS ratings were significantly higher in females as
      compared to males (24 +/- 15 vs. 18 +/- 5 mm, P < 0.05), however, when corrected
      for PR change while walking, they were not different. The equation by stepwise
      multiple regression analysis included height, age and gender for the 6MWD and
      accounted for 42% of the total variance. This study confirms the relevant effect
      of anthropometrics on walking capacity and suggests that when rating dyspnea, the
      change in heart rate during walking should be considered.

PMID- 16466678
TI  - Functional network of the basal ganglia and cerebellar motor loops in vivo:
      different activation patterns between self-initiated and externally triggered
      movements.
AB  - The basal ganglia and cerebellar loops are known to participate differently in
      self-initiated (SI) and externally triggered (ET) movements. However, no previous
      neuroimaging studies have illustrated functional organization of these loops in
      vivo. Here, we aimed to functionally visualize these loops during motor execution
      using functional magnetic resonance imaging (fMRI) with structural equation
      modeling (SEM). Twelve normal subjects (24-29 years old) were scanned while
      performing five different frequencies of sequential left finger movements using
      either SI or ET movements. Random effect analysis combined with a parametric
      approach revealed a significant positive linear dependence of cerebral activation
      upon movement rate in the right Put, GPi, VL, SMC and SMA during SI tasks. During
      ET tasks, significant positive linear relationships were found in the right SMC,
      VPL, left CB and DN, whereas tendency for linear relationships was seen in the
      right PMv. SEM further showed significant interactions within the right basal
      ganglia-thalamo-motor loop during SI tasks. In contrast, there were significant
      interactions within the entire right cerebral hemisphere-left cerebellar loop
      involving CB, DN, VPL, PMv and SMC during ET tasks. Therefore, our modeling
      approach enabled identification of different contributions of the motor loops of
      basal ganglia and cerebellum to SI and ET tasks during motor execution.

PMID- 16466679
TI  - Information processing in human parieto-frontal circuits during goal-directed
      bimanual movements.
AB  - It is known that, in macaques, movements guided by somatosensory information
      engage anterior parietal and posterior precentral regions. Movements performed
      with both visual and somatosensory feedback additionally activate posterior
      parietal and anterior precentral areas. It remains unclear whether the human
      parieto-frontal circuits exhibit a similar functional organization. Here, we
      employed a directional interference task requiring a continuous update of sensory
      information for the on-line control of movement direction, while brain activity
      was measured by functional magnetic resonance imaging (fMRI). Directional
      interference arises when bimanual movements occur along different directions in
      joint space. Under these circumstances, the presence of visual information does
      not substantially alter performance, such that we could vary the amount and type
      of sensory information used during on-line guidance of goal-directed movements
      without affecting motor output. Our results confirmed that in humans, as in
      macaques, movements guided by somatosensory information engages anterior parietal
      and posterior precentral regions, while movements performed with both visual and
      somatosensory information activate posterior parietal and anterior precentral
      areas. We provide novel evidence on how the interaction of specific portions of
      the dorsal parietal and precentral cortex in the right hemisphere might generate
      spatial representations by integrating different sensory modalities during goal
      directed movements.

PMID- 16466680
TI  - Self-referential processing in our brain--a meta-analysis of imaging studies on
      the self.
AB  - The question of the self has intrigued philosophers and psychologists for a long
      time. More recently, distinct concepts of self have also been suggested in
      neuroscience. However, the exact relationship between these concepts and neural
      processing across different brain regions remains unclear. This article reviews
      neuroimaging studies comparing neural correlates during processing of stimuli
      related to the self with those of non-self-referential stimuli. All studies
      revealed activation in the medial regions of our brains' cortex during self
      related stimuli. The activation in these so-called cortical midline structures
      (CMS) occurred across all functional domains (e.g., verbal, spatial, emotional,
      and facial). Cluster and factor analyses indicate functional specialization into
      ventral, dorsal, and posterior CMS remaining independent of domains. Taken
      together, our results suggest that self-referential processing is mediated by
      cortical midline structures. Since the CMS are densely and reciprocally connected
      to subcortical midline regions, we advocate an integrated cortical-subcortical
      midline system underlying human self. We conclude that self-referential
      processing in CMS constitutes the core of our self and is critical for
      elaborating experiential feelings of self, uniting several distinct concepts
      evident in current neuroscience.

PMID- 16466681
TI  - Metabolic engineering of the E. coli L-phenylalanine pathway for the production
      of D-phenylglycine (D-Phg).
AB  - D-phenylglycine (D-Phg) is an important side chain building block for semi
      synthetic penicillins and cephalosporins such as ampicillin and cephalexin. To
      produce d-Phg ultimately from glucose, metabolic engineering was applied.
      Starting from phenylpyruvate, which is the direct precursor of L-phenylalanine,
      an artificial D-Phg biosynthesis pathway was created. This three-step route is
      composed of the enzymes hydroxymandelate synthase (HmaS), hydroxymandelate
      oxidase (Hmo), and the stereoinverting hydroxyphenylglycine aminotransferase
      (HpgAT). Together they catalyse the conversion of phenylpyruvate via mandelate
      and phenylglyoxylate to D-Phg. The corresponding genes were obtained from
      Amycolatopsis orientalis, Streptomyces coelicolor, and Pseudomonas putida.
      Combined expression of these activities in E. coli strains optimized for the
      production of L-phenylalanine resulted in the first completely fermentative
      production of D-Phg.

PMID- 16466682
TI  - Fibroblast growth factor 2 and cyclic AMP synergistically regulate bone
      sialoprotein gene expression.
AB  - Bone sialoprotein (BSP) is a noncollagenous protein of the mineralized bone
      extracellular matrix. We here report that FGF2 and cAMP act synergistically to
      stimulate BSP gene expression. Treatment of ROS 17/2.8 cells with either 10 ng/ml
      FGF2 or 1 microM FSK for 6 h resulted in 5.4- and 8.2-fold increases,
      respectively, in the levels of BSP mRNA. However, in the presence of both FGF2
      and forskolin (FGF/FSK), BSP mRNA levels were increased synergistically by 20.4
      fold. Using a luciferase reporter construct, encompassing BSP promoter
      nucleotides -116 to +60, transcription was also increased synergistically by 15.0
      fold with FGF/FSK, compared to stimulations of 2.6- and 5.3-fold, respectively,
      for FGF2 and FSK alone. Transcriptional stimulation by FGF/FSK abrogated in
      constructs included 2 bp mutations in the inverted CCAAT, CRE, FRE and Pit-1
      elements. Whereas the FRE-protein complex was increased by FGF2 and FGF/FSK, the
      Pit-1-protein complex was decreased by FSK and FGF/FSK. Notably, transcriptional
      activity induced by FGF/FSK was blocked by protein kinase A, tyrosine kinase and
      MEK inhibitors. These studies indicate that the combinatorial effects of FGF and
      FSK act through PKA, tyrosine kinase and MAP-kinase-dependent pathways, which
      target the inverted CCAAT, CRE, FRE and Pit-1 elements in the BSP gene to
      synergistically increase BSP expression.

PMID- 16466683
TI  - Response preparation modulates interference from irrelevant spatial information.
AB  - This study explored the effects of response cues on interference from irrelevant
      spatial stimulus information (i.e. on the Simon effect). Previous studies, which
      have always used unreliable response cues, consistently found that valid response
      cues increase the Simon effect, when compared to a neutral-cue condition. Two
      experiments tested possible explanations for the effects of response cues on the
      Simon effect by comparing the effects of unreliable cues to those of reliable
      cues. The response-speed hypothesis predicts that unreliable and reliable
      response cues should increase Simon effects, when compared to neutral cues. In
      contrast, the event-coding hypothesis predicts opposite effects of unreliable and
      reliable response cues on the Simon effect. Experiment 1 (unreliable cues)
      replicated previous results: valid cues increased, invalid cues decreased Simon
      effects. Experiment 2 (reliable cues) showed the opposite results: valid cues
      decreased Simon effects. The results support the event-coding hypothesis, which
      assumes that response preparation with unreliable cues and response preparation
      with reliable cues are qualitatively different.

PMID- 16466684
TI  - [Minimally invasive esophagectomy: prospective evaluation of laparoscopic gastric
      mobilization].
AB  - OBJECTIVE: Esophagectomy carries high morbidity, mainly due to respiratory
      complications. In digestive surgery, postoperative outcome is generally improved
      by minimally invasive surgery. A prospective study was conducted to evaluate
      feasibility and postoperative outcome of minimally invasive esophagectomy (MIE).
      METHODS: From July 2001 to June 2004, 20 patients underwent esophagectomy with
      laparoscopic gastric mobilization (LGM) for squamous cell carcinoma (N=11),
      adenocarcinoma (N=7), Barrett's esophagus with high-grade dysplasia (N=1), and
      long peptic stricture (N=1). Tumours (N=19) were located on the cardia (N=5), on
      the lower third of the oesophagus (N=10), on the median third (N=3), and on the
      upper third (N=1). Following LGM, transthoracic (N=19) or transhiatal (N=1)
      oesophagectomy was performed. RESULTS: Complete LGM was achieved in all cases.
      Mean operative time for LGM was 197+/-48 minutes. In the 19 patients operated for
      tumours, 18 underwent R0 resection. Eleven patients (55%) developed postoperative
      complications, mainly (30%) respiratory. Intrathoracic anastomotic leakage
      occurred in 2 patients, with favourable outcome. Pylorospasm (N=1) was the only
      intraabdominal complication. One patient died (5%). CONCLUSION: Esophagectomy
      with LGM is feasible with few specific complications. However, no decrease in
      morbidity could be observed with this technique. Further studies are required to
      evaluate if thoracoscopy could improve the postoperative course after LGM and to
      validate oncologic safety of MIE.

PMID- 16466685
TI  - Fatty acid transport by vectorial acylation in mammals: roles played by different
      isoforms of rat long-chain acyl-CoA synthetases.
AB  - Mammals express multiple isoforms of acyl-CoA synthetase (ACSL1 and ACSL3-6) in
      various tissues. These enzymes are essential for fatty acid metabolism providing
      activated intermediates for complex lipid synthesis, protein modification, and
      beta-oxidation. Yeast in contrast express four major ACSLs, which have well
      defined functions. Two, Faa1p and Faa4p, are specifically required for fatty acid
      transport by vectorial acylation. Four ACSLs from the rat were expressed in a
      yeast faa1delta faa4delta strain and their roles in fatty acid transport and
      trafficking characterized. All four restored ACS activity yet varied in substrate
      preference. ACSL1, 4, and 6 were able to rescue fatty acid transport activity and
      triglyceride synthesis. ACSL5, however, was unable to facilitate fatty acid
      transport despite conferring robust oleoyl-CoA synthetase activity. This is the
      first study evaluating the role of the mammalian ACSLs in fatty acid transport
      and supports a role for ACSL1, 4, and 6 in transport by vectorial acylation.

PMID- 16466686
TI  - Topological role of cytochrome P450 2D6 active site residues.
AB  - Recent reports have identified Phe120, Asp301, Thr309, and Glu216 as important
      residues in cytochrome P450 2D6 (CYP2D6) substrate binding and catalysis.
      Complementary homology models have located these amino acids within the binding
      pocket of CYP2D6 and in the present study we have used aryldiazenes to test these
      models and gain further insight in the role these amino acids have in maintaining
      the integrity of the active site cavity. When Phe120 was replaced to alanine,
      there was a significant increase in probe migration to pyrrole nitrogens C and D,
      in agreement with homology models which have located the phenyl side-chain of
      Phe120 above these two pyrrole rings. No changes in topology were observed with
      the D301Q mutant, supporting claims that in this mutant the electrostatic
      interactions with the B/C-loop are largely maintained and the loop retains its
      native orientation. The T309V mutation resulted in significant topological
      alteration suggesting that, in addition to its potential role in dioxygen
      activation, Thr309 plays an important structural role within the active site
      crevice. Replacement of Ile106 with Glu, engineered to cause electrostatic
      repulsion with Glu216, had a profound topological effect in the higher region
      within the active site cavity and impaired the catalytic activity towards CYP2D6
      probe substrates.

PMID- 16466687
TI  - c-Jun N-terminal kinase regulates CTP:phosphocholine cytidylyltransferase.
AB  - CTP:phosphocholine cytidylyltransferase (CCTalpha) is a rate-regulatory enzyme
      required for phosphatidylcholine (PtdCho) synthesis. CCTalpha is also a
      phosphoenzyme, but the physiologic role of kinases on enzyme function remains
      unclear. We report high-level expression of two major isoforms of the c-Jun N
      terminal kinase family (JNK1 and JNK2) in murine lung epithelia. Further, JNK1
      and JNK2 phosphorylated purified CCTalpha in vitro, and this was associated with
      a dose-dependent decrease (approximately 40%) in CCT activity. To evaluate JNK in
      vivo, lung epithelial cells were infected with a replication defective adenoviral
      vector encoding murine JNK2 (Adv-JNK2) or an empty vector. Adv-JNK2 infection,
      unlike the empty vector, markedly increased JNK2 expression concomitant with
      increased incorporation of [32P]orthophosphate into endogenous CCTalpha. Although
      Adv-JNK2 infection only modestly reduced CCT activity, it reduced PtdCho
      synthesis by approximately 30% in cells. These observations suggest a role for
      JNK kinases as negative regulators of phospholipid synthesis in murine lung
      epithelia.

PMID- 16466688
TI  - Videoconferencing-based cognitive-behavioral therapy for obsessive-compulsive
      disorder.
AB  - Obsessive-compulsive disorder (OCD) is a prevalent, chronic and disabling anxiety
      disorder. Despite the efficacy and strength of pharmacologic interventions for
      OCD, medications are not always well accepted or effective, making an efficacious
      psychosocial alternative especially attractive. Cognitive-behavioral therapy
      (CBT) has been established as an effective treatment for adult OCD, yet access to
      such treatment is limited, especially in rural areas. Technological advances
      allow for therapy to be provided in a real-time format over a videoconferencing
      network. This method allows therapists to provide state-of-the-art treatment to
      patients who would not otherwise have access to it. This paper presents three
      cases of OCD successfully treated via videoconferencing CBT. The presence of OCD
      was established via structured clinical interview and clinician-rated outcome
      measures were completed by evaluators blinded to the method of treatment. A
      multiple baseline across individuals design was used to support the internal
      validity of the CBT outcome data. Patient ratings of therapeutic alliance were
      high across all three cases. Information gathered from qualitative interviews
      post-treatment confirmed quantitative measures finding high levels of patient
      satisfaction. This pilot study suggests that videoconferencing-based CBT is a
      promising method to bring appropriate treatment to thousands who live far
      distances from well-trained therapists.

PMID- 16466689
TI  - A specific N-terminal residue in Kv1.5 is required for upregulation of the
      channel by SAP97.
AB  - We have previously reported that SAP97 enhancement of hKv1.5 currents requires an
      intact Kv1.5 N-terminus and is independent of the PDZ-binding motif at the C
      terminus of the channel [J. Eldstrom, W.S. Choi, D.F. Steele, D. Fedida, SAP97
      increases Kv1.5 currents through an indirect N-terminal mechanism, FEBS Lett. 547
      (2003) 205-211]. Here, we report that an interaction between the two proteins can
      be detected under certain conditions but their interaction is irrelevant to the
      enhancement of channel expression. Instead, a threonine residue at position 15 in
      the hKv1.5 N-terminus is critically important. Mutation of this residue, which
      lies within a consensus site for phosphorylation by protein kinase C, to an
      alanine, completely abrogated the effect of SAP97 on channel expression. Although
      we were unable to detect phosphorylation of this residue, specific inhibition of
      kinase C by Calphostin C eliminated the increase in wild-type hKv1.5 currents
      associated with SAP97 overexpression suggesting a role for this kinase in the
      response.

PMID- 16466690
TI  - Oxidized low density lipoprotein suppresses lipopolysaccharide-induced
      inflammatory responses in microglia: oxidative stress acts through control of
      inflammation.
AB  - Low density lipoprotein (LDL) is readily oxidized under certain conditions,
      resulting in the formation of oxidized LDL (oxLDL). Despite numerous in vitro
      reports that reveal the pathogenic role of oxidative stress, anti-oxidative
      strategies have underperformed in the clinic. In this study, we examine the role
      of oxLDL in brain inflammatory responses using cultured rat brain microglia. We
      demonstrate that oxLDL inhibits lipopolysaccharide (LPS)-induced inflammatory
      responses in these cells. It also decreases LPS-induced expression of inducible
      nitric oxide synthase and production of nitric oxide, and reduces LPS-induced
      secretion of tumor necrosis factor-alpha and monocyte chemoattractant protein-1.
      Oxysterols, known components of oxLDL and endogenous agonists of liver X
      receptor, can simulate the inhibitory effects of oxLDL in LPS-activated
      microglia. In addition, their inhibitory effects were mimicked by liver X
      receptor (LXR) agonists and potentiated by a retinoid X receptor agonist,
      suggesting these molecules heterodimerize to function as oxysterol receptors.
      Taken together, our results demonstrate that oxLDL inhibits LPS-induced
      inflammatory responses in brain microglia and that these inhibitory effects are
      mediated by oxysterols and, at least in part, by the nuclear receptor LXR. Our
      results suggest an additional mechanism of action for oxidative stress that acts
      indirectly via modulation of inflammatory responses. Although further studies are
      needed, these results answer in part the question of why anti-oxidative
      strategies have not been successful in clinical situations. Moreover, as brain
      inflammation participates in the initiation and progression of several
      neurodegenerative disorders, the present data provide information that should
      prove a useful guide for designing therapeutic strategies to combat oxidative
      brain diseases.

PMID- 16466691
TI  - A G protein gamma subunit peptide stabilizes a novel muscarinic receptor state.
AB  - A prenylated peptide specific to the C terminal tail of a G protein gamma subunit
      type, gamma5, inhibits activation of a G protein by the M2 muscarinic receptor.
      The gamma5 peptide was tested for direct effects on the M2 receptor's properties.
      The wild type gamma5 peptide reduced the affinity of M2 for the agonist,
      carbachol, more than 5-fold in an antagonist displacement assay. The peptide was
      inactive when its amino acid sequence was scrambled or when it was unprenylated.
      Although the wild type peptide reduced the affinity of M2 for the antagonist QNB,
      it had no effect on the antagonists NMS or atropine. These results suggest that
      in the presence of the peptide the M2 receptor adopts a novel conformational
      state that affects the ligand binding surface. The results also suggest that the
      G protein gamma5 subunit tail interacts with a receptor.

PMID- 16466692
TI  - Stimulation of the creatine transporter SLC6A8 by the protein kinase mTOR.
AB  - Cellular accumulation of creatine is accomplished by the Na(+), Cl(-), and
      creatine transporter CreaT (SLC6A8). The mammalian target of rapamycin (mTOR) is
      a kinase stimulating cellular nutrient uptake. The present experiments explored
      whether SLC6A8 is regulated by mTOR. In Xenopus oocytes expressing SLC6A8 but not
      in water injected oocytes, creatine-induced a current which was significantly
      enhanced by coexpression of mTOR. Kinetic analysis revealed that mTOR enhanced
      maximal current without significantly altering affinity. Preincubation of the
      oocytes for 32 h with rapamycin (50 nM) decreased the creatine-induced current
      and abrogated its stimulation by mTOR. The effect of mTOR on CreaT was blunted by
      additional coexpression of the inactive mutant of the serum and glucocorticoid
      inducible kinase (K119N)SGK1 and mimicked by coexpression of wild type SGK1. In
      conclusion, mTOR stimulates the creatine transporter SLC6A8 through mechanisms at
      least partially shared by the serum and glucocorticoid-inducible kinase SGK1.

PMID- 16466693
TI  - The neuropeptide neuromedin U promotes IL-6 production from macrophages and
      endotoxin shock.
AB  - Neuromedin U (NMU) is a neuropeptide involved in appetite, circadian rhythm, and
      pronociception. However, the NMU receptor NMU-R1 has been shown to be expressed
      in immune cells and NMU promotes mast cell-dependent inflammation. In this study,
      we demonstrated that NMU plays an important role in IL-6 production in
      macrophages. NMU-deficient mice were resistant against cecal ligation puncture-
      as well as LPS-induced septic shock. IL-6 but not TNF-alpha levels were markedly
      reduced in LPS-treated NMU-deficient mice compared with wild type mice. Both NMU
      and NMU-R1 were expressed in wild type peritoneal macrophages, and treatment with
      LPS resulted in up-regulation of NMU but down-regulation of NMU-R1 expression,
      however, no down-regulation of NMU-R1 was observed in NMU-deficient macrophages
      where LPS-induced IL-6 production was severely reduced. These data suggest that
      LPS-induced IL-6 expression is partly dependent on autocrine/paracrine activation
      of the NMU-NMU-R1 signals in macrophages.

PMID- 16466694
TI  - In vivo analysis of fibroin heavy chain signal peptide of silkworm Bombyx mori
      using recombinant baculovirus as vector.
AB  - In order to investigate the functional signal peptide of silkworm fibroin heavy
      chain (FibH) and the effect of N- and C-terminal parts of FibH on the secretion
      of FibH in vivo, N- and C-terminal segments of fibh gene were fused with enhanced
      green fluorescent protein (EGFP) gene. The fused gene was then introduced into
      silkworm larvae and expressed in silk gland using recombinant AcMNPV (Autographa
      californica multiple nuclear polyhedrosis virus) as vector. The fluorescence of
      EGFP was observed with fluorescence microscope. FibH-EGFP fusion proteins
      extracted from silk gland were analyzed by Western blot. Results showed that the
      two alpha helices within N-terminal 163 amino acid residues and the C-terminal 61
      amino acid residues were not necessary for cleavage of signal peptide and
      secretion of the fusion protein into silk gland. Then the C-terminal 61 amino
      acid residues were substituted with a His-tag in the fusion protein to facilitate
      the purification. N-terminal sequencing of the purified protein showed that the
      signal cleavage site is between position 21 and 22 amino acid residues.

PMID- 16466695
TI  - Endothelin-1 gene variants and levels associate with adaptation to hypobaric
      hypoxia in high-altitude natives.
AB  - High-altitude natives are adapted to hypobaric hypoxia, suggestive of genetic
      basis of adaptation. Since endothelin-1 (ET-1) is of prime importance in high
      altitude disorders in sojourners, we envisaged the role of allelic variants of ET
      1 in high-altitude adaptation. Four ET-1 polymorphisms, viz., (CT)(n)-(CA)(n)
      repeat, -3A/-4A, G2288T, and Lys198Asn, were investigated in 426 highlanders
      (HLs) and 236 lowlanders (LLs). The plasma ET-1 levels, SBP and BMI were
      significantly lower in the HLs than those in LLs (p<0.0001). The Longer-repeats
      (31-45), G allele, Longer-repeats/GG, and Longer-repeats/Lys198Lys combinations
      were overrepresented in the HLs (p<0.0001, p=0.03, p<0.0001, and p<0.0001,
      respectively). The Longer-repeats, -3A/-3A, GG and Lys198Lys genotypes associated
      with significantly lower ET-1 levels in the HLs (p<0.0001, p=0.001, p<0.0001, and
      p<0.0001, respectively). Combinations of Longer-repeats with -3A/-3A, GG, and
      Lys198Lys genotypes, and -3A/-3A/Lys198Lys combination revealed association with
      lower ET-1 levels in the HLs (p<0.001). The study reports over-representation of
      Longer-repeats, G allele, and wild-type genotype combinations in high-altitude
      natives. Interaction between these alleles and association with lower ET-1 levels
      strengthen their association with high-altitude adaptation. Presence of such
      alleles in sojourners may help in acclimatization.

PMID- 16466696
TI  - An endogenous acid-sensitive K+ channel expressed in COS-7 cells.
AB  - COS-7 cells originally isolated from monkey kidney and used in many transfection
      studies were found to express a background K+ channel and therefore, its
      biophysical and pharmacological properties were examined. In cell-attached
      patches, a 32-pS K+ channel with a linear current-voltage relationship could be
      recorded. The open probability was highly voltage-dependent, with greater channel
      activity at depolarized potentials. The channel was markedly sensitive to changes
      in extracellular pH (pH(o)), showing a 70+/-10% inhibition by changing the pH(o)
      from 7.3 to 6.3. Arachidonic acid (5 microM) augmented channel activity 12-fold.
      Applying negative pressure (-40 mmHg) to the membrane patch also increased
      channel activity by 4-fold. These results show that COS-7 cells express a K+
      channel with unique properties that must be considered when using these cells as
      transfection system.

PMID- 16466697
TI  - Shear stress regulation of Kruppel-like factor 2 expression is flow pattern
      specific.
AB  - Flow patterns in blood vessels contribute to focal distribution of
      atherosclerosis; the underlying mechanotransduction pathways remain to be
      investigated. We demonstrate that different flow patterns elicit distinct
      responses of Kruppel-like factor-2 (KLF2) in endothelial cells (ECs) in vitro and
      in vivo. While pulsatile flow with a significant forward direction induced
      sustained expression of KLF2 in cultured ECs, oscillatory flow with little
      forward direction caused prolonged suppression after a transient induction. The
      suppressive effect of oscillatory flow was Src-dependent. Immunohistochemical
      studies on ECs at arterial branch points revealed that KLF2 protein levels were
      related to local hemodynamics. Such flow-associated expression patterns were also
      demonstrated in a rat aortic restenosis model. Inhibition of KLF2 with siRNA
      sensitized ECs to oxidized LDL-induced apoptosis, indicating a protective role of
      KLF2. In conclusion, differential regulation of KLF2 may mediate the distinct
      vascular effects induced by various patterns of shear stress.

PMID- 16466698
TI  - Analytical assays of human HSP27 and thermal-stress survival of Escherichia coli
      cells that overexpress it.
AB  - HSP27 is a small heat-shock protein (sHSP). Such proteins are produced in all
      organisms. These small HSPs exhibit chaperone-like activity that can bind to
      unfolded polypeptides and prevent uncontrolled protein aggregation in vitro.
      Cellular anti-apoptosis function and enhanced cell survival are correlated with
      increased expression of HSPs. This study presents a thermal-stress survival model
      for cells using the Escherichia coli expression system for which human HSP27, a
      recombinant protein, is inducible. Results show that E. coli cells overexpressing
      human HSP27 have enhanced tolerance to 50 degrees C thermal stress.

PMID- 16466699
TI  - Osterix enhances proliferation and osteogenic potential of bone marrow stromal
      cells.
AB  - Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed
      in osteoblasts of all endochondral and membranous bones. In Osx null mice
      osteoblast differentiation is impaired and bone formation is absent. In this
      study, we hypothesized that overexpression of Osx in murine bone marrow stromal
      cells (BMSC) would be able to enhance their osteoblastic differentiation and
      mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non
      differentiating medium did not affect expression of Runx2/Cbfa1, another key
      transcription factor of osteoblast differentiation, but induced an increase in
      the expression of other markers associated with the osteoblastic lineage
      including alkaline phosphatase, bone sialoprotein, osteocalcin, and osteopontin.
      Retroviral transduction of Osx in BMSC also increased their proliferation,
      alkaline phosphatase activity, and ability to form bone nodules. These events
      occurred without significant changes in the expression of alpha1(II) procollagen
      or lipoprotein lipase, which are markers of chondrogenic and adipogenic
      differentiation, respectively.

PMID- 16466700
TI  - c-Myc over-expression in Ramos Burkitt's lymphoma cell line predisposes to iron
      homeostasis disruption in vitro.
AB  - Burkitt's lymphoma is an aggressive B-cell neoplasm resulting from deregulated c
      myc expression. We have previously shown that proliferation of Burkitt's lymphoma
      cell lines such as Ramos is markedly reduced by iron treatment. It has been shown
      that iron induces expression of c-myc which, owing to its transcriptional
      regulatory functions, regulates genes involved in iron metabolism. Transient
      enhancement of c-myc expression by iron could increase the expression of genes
      involved in iron incorporation, which could lead to an accumulation of
      intracellular free iron. Here, we have investigated whether cells with a high
      basal level of c-Myc were more likely to accumulate free iron. Our results
      suggest that the basal level of c-Myc in Ramos cells is twofold higher than what
      is seen in HL-60 cells. Moreover, in Ramos cells, where c-Myc is expressed at a
      high level, H-ferritin expression is down-regulated, transferrin receptor (CD71)
      expression is increased, and ferritin translation is inhibited. These
      modifications in iron metabolism, resulting from the strong basal expression of c
      Myc, and amplified by iron addition, could lead to a disruption in homeostasis
      and consequently to growth arrest.

PMID- 16466701
TI  - Hexadecylphosphocholine disrupts cholesterol homeostasis and induces the
      accumulation of free cholesterol in HepG2 tumour cells.
AB  - Hexadecylphosphocholine (HePC) is a synthetic lipid belonging to the
      alkylphosphocholines (APC), a new group of antiproliferative agents that are
      proving to be promising candidates in anticancer therapy. We reported in a
      previous study that HePC interferes with phosphatidylcholine (PC) synthesis in
      HepG2 cells via both CDP-choline and phosphatidylethanolamine (PE) methylation.
      We have subsequently extended our studies to show that HePC interferes with
      sphingolipid metabolism by hindering the formation of sphingomyelin (SM), an
      effect accompanied by a substantial increase in the incorporation of the
      exogenous lipogenic precursors into ceramides. Interestingly, we demonstrate for
      the first time that HePC strongly inhibits the esterification of free cholesterol
      (FC) by acting at the level of acyl CoA:cholesterol acyltransferase (ACAT) (EC
      2.3.1.26) activity. This effect is accompanied by a considerable increase in the
      synthesis of cholesterol, which leads to a rise in the levels of FC in cells. We
      are left in no doubt that the imbalance in the metabolism of membrane-lipid
      components vital to cell survival may well be responsible for the observed DNA
      fragmentation and activation of caspase-3, an enzyme involved in the cell
      apoptosis found in this study.

PMID- 16466702
TI  - Prion protein mRNA expression in Xenopus laevis: no induction during melanotrope
      cell activation.
AB  - In mammals, the prion protein (PrP) is expressed in most tissues, but
      predominantly in neuronal tissues. Here, we investigated the temporal and spatial
      mRNA expression of PrP in the non-mammalian South African claw-toed frog Xenopus
      laevis. PrP transcripts were maternally expressed and detected throughout
      embryonic development, most strongly from neurulation onwards and including the
      tadpole stage. Microinjection of PrP mRNA into fertilized Xenopus eggs did not
      affect early embryonic development. In adult frogs, PrP mRNA expression was
      observed in all tissues examined, with high expression in brain, pituitary and
      testis. In Xenopus, the intermediate pituitary melanotrope cells are involved in
      background adaptation of the animal and produce high levels of the prohormone
      proopiomelanocortin (POMC) when the melanotrope cells are active (i.e. when the
      animal is black-adapted). Remarkably and in contrast to most secretory pathway
      components, PrP was not upregulated in the melanotropes of black-adapted animals,
      arguing against a direct role of this protein in POMC biosynthesis.

PMID- 16466703
TI  - Dystrophin is a possible end-target of ischemic preconditioning against
      cardiomyocyte oncosis during the early phase of reperfusion.
AB  - OBJECTIVE: Dystrophin is a sarcolemmal membrane protein that prevents the myocyte
      from oncosis induced by physical stress. Because ischemic preconditioning (IPC)
      protects mitochondria and prevents oncosis during reperfusion, we hypothesized
      that dystrophin is an end-target of IPC distal to mitochondrial protection.
      METHODS AND RESULTS: Isolated rat hearts were subjected to 30 min ischemia
      followed by reperfusion. IPC was introduced by 3 cycles of 5 min ischemia and 5
      min reperfusion. The loss of sarcolemmal dystrophin and myocardial ATP during
      ischemia was comparable between the control and the IPC heart. Similar changes in
      sarcolemmal dystrophin and myocardial ATP were observed when the heart was
      treated with 2,4-dinitrophenol (DNP), an uncoupler of mitochondrial respiration,
      or oligomycin, an inhibitor of mitochondrial F1F0-ATPase. However, the IPC heart
      increased sarcolemmal dystrophin during reperfusion associated with an increase
      in tetramethylrhodamine ethylester (TMRE) uptake, an indicator of mitochondrial
      membrane potential (DeltaPsim), and myocardial ATP and inhibited myocyte oncosis.
      The increase in myocardial ATP and relocalization of dystrophin to the sarcolemma
      mediated by IPC was inhibited by treatment with DNP or oligomycin during
      reperfusion. In vitro experiments demonstrated that mitochondria isolated from
      the ischemic IPC heart increased ATP generation and facilitated relocalization of
      dystrophin from the insoluble to the soluble fractions in a manner sensitive to
      DNP and oligomycin. CONCLUSIONS: These results suggest that enhanced
      relocalization of dystrophin to the sarcolemma during reperfusion may be a
      mechanistic link between IPC-mediated improvement of mitochondrial function and
      its protection against oncosis during the early phase of reperfusion.

PMID- 16466704
TI  - Integrin signalling: the tug-of-war in heart hypertrophy.
AB  - The mechanical stress imposed by hemodynamic overload on heart walls is a primary
      event in triggering the cardiac hypertrophic response. Integrins, a class of
      membrane receptors, are major players in transmitting the mechanical force across
      the plasma membrane and sensing the mechanical load in cardiomyocytes. In fact,
      integrins, together with a number of associated cytoskeletal proteins, connect
      the sarcomeric contractile apparatus to the extracellular matrix across the
      plasma membrane and trigger intracellular signaling pathways activating the
      cardiomyocyte hypertrophy program. In this review, we will discuss the role of
      the muscle-specific integrin isoform beta1D and of associated proteins such as
      FAK, melusin, vinculin, zyxin, VASP, and migfilin that are the most upstream
      elements ("initiators") activated by mechanical strain. These molecules trigger a
      coordinated downstream signaling cascade involving proteins such as AKT, RAS, and
      MAPKs that execute the biochemical program leading to cardiomyocyte hypertrophy.
      Better understanding of the functional role of the initiator elements is of key
      importance to developing novel strategies to control cardiac hypertrophy and
      prevent heart failure.

PMID- 16466705
TI  - Evaluation of various housekeeping genes for their applicability for
      normalization of mRNA expression in dioxin-treated rats.
AB  - Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is an
      extremely sensitive, convenient and rapid method to measure mRNA levels in cells
      and tissues, and is gaining popularity in toxicology. To correct for sample-to
      sample variation, normalization of the expression data is required. The
      conventional way to perform normalization is to select a reference gene whose
      expression is believed to remain stable across all experimental conditions, then
      relate the concentrations of gene(s) of interest to those of this housekeeping
      gene. Since recent evidence shows that some housekeeping genes are actually not
      as refractory to experimental manipulations as previously thought, we validated a
      large number (18) of commonly used housekeeping genes for acute toxicity studies
      of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an extremely potent environmental
      toxin known to regulate a wide variety of genes. Microarray and qRT-PCR analyses
      coherently demonstrated that about 50% of the housekeeping genes examined were
      responsive to TCDD in rat liver with the magnitudes of change up to nearly 10
      fold. Extension of the study to spleen and hypothalamus verified that
      phosphoglycerate kinase 1 (Pgk1) and glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) retained their basal expression levels in all experimental settings,
      although body weight loss-generated repression may mask a slight induction of
      GAPDH by TCDD in liver. These findings show that normalization genes for qRT-PCR
      must be carefully validated in advance, especially if the study involves a potent
      modifier of gene expression.

PMID- 16466706
TI  - In vitro effect of homocysteine on nucleotide hydrolysis by blood serum from
      adult rats.
AB  - During the past few years, elevated blood levels of homocysteine (Hcy) have been
      linked to increased risk of premature coronary artery disease, stroke and
      thromboembolism. These processes can be also related to the ratio adenine
      nucleotide/adenosine, since extracellularly these nucleotides are associated with
      modulation of processes such as platelet aggregation, vasodilatation and coronary
      flow. Furthermore, there are some studies that suggest a relationship between Hcy
      and plasma adenosine concentrations. The sequential hydrolysis of ATP to
      adenosine by soluble nucleotidases constitutes one of the systems for rapid
      inactivation of circulating adenine nucleotides. Thus, the main objective of this
      study was to evaluate if Hcy can participate in the modulation of the
      extracellular adenine nucleotide hydrolysis by rat blood serum. Our results
      showed that Hcy, at final concentrations of 5.0 mM, inhibits in vitro ATP, ADP
      and AMP hydrolysis by 26, 21 and 16%, respectively. Also Hcy, at final
      concentrations of 8.0mM, inhibited the in vitro hydrolysis of ATP, ADP and AMP by
      46, 44 and 44%, respectively. Kinetic analysis showed that the inhibitions of the
      three adenine nucleotide hydrolyses in the presence of Hcy, by serum of adult
      rats, is of the uncompetitive type. The IC50 calculated from the results obtained
      were 6.52+/-1.75 mM (n = 4), 5.18 +/- 0.64 mM (n = 3) and 5.16 +/- 1.22 mM (n =
      3) for ATP, ADP and AMP hydrolysis, respectively.

PMID- 16466707
TI  - Haplotype analysis of UDP-glucuronocyltransferase 2B7 gene (UGT2B7) polymorphisms
      in healthy Japanese subjects.
AB  - OBJECTIVES: UDP-glucuronocyltransferase 2B7 (UGT2B7) catalyzes glucuronidation of
      various types of endogenous compounds and drugs, but the genetic basis of
      interindividual variation in the metabolism of these substances has not yet been
      sufficiently elucidated. In addition, information about single nucleotide
      polymorphisms (SNPs) and haplotypes of the UGT2B7 gene that encode the enzyme in
      the Japanese population is still far from sufficient. DESIGN AND METHODS: We paid
      special attention to and performed an investigation on -327A > G, -161T > C, 
      138G > A, and -125T > C in the proximal promoter region, which is regarded as
      being important for the transcription of the UGT2B7 gene, and also on 211G > A
      and 802C > T, i.e., non-synonymous SNPs of exon 1 and exon 2 that encode the
      substrate binding domain. Their genotypes were determined by PCR-direct
      sequencing. RESULTS: As a result of genotyping, the minor allele frequencies in
      160 Japanese individuals were found to be as follows: -327SNP A allele, 0.244; 
      161SNP T allele, 0.244; -138SNP A allele, 0; -125SNP C allele, 0.078; 211SNP T
      allele, 0.148 and 802SNP T allele, 0.244. By computational haplotype analysis, it
      was found that these regions formed a linkage disequilibrium block, and the
      presence of five haplotypes was demonstrated. CONCLUSIONS: These results suggest
      that the haplotype structure in the Japanese population is different from that of
      other ethnic groups.

PMID- 16466708
TI  - Thyroid function during B-vitamin supplementation of patients on antiepileptic
      drugs.
AB  - OBJECTIVES: Patients on antiepileptic drugs (AEDs) may have low serum
      concentrations of thyroxine, with or without a compensatory increment in thyroid
      stimulating hormone (TSH). Furthermore, patients on AEDs often have
      hyperhomocysteinemia and low concentrations of vitamins B(6), B(2) and folate.
      Previously, an inverse relationship between thyroxine and homocysteine
      concentrations has been observed. In animals, deficiency of vitamin B(6) has been
      found to impair the hypophyseal release of TRH. We have studied the effect of B
      vitamin supplements on thyroid function in patients on AEDs. DESIGN AND METHODS:
      Thirty-two patients on AEDs were identified with hyperhomocysteinemia and low
      folate, B(6) and B(2). They were supplemented with pyridoxine, riboflavin and
      folic acid for 30 days. RESULTS: At baseline, the patients had low serum
      concentrations of free thyroxin and slightly elevated TSH. On day 30 of the B
      vitamin supplements, homocysteine had decreased, however, the thyroid parameters
      remained unchanged. CONCLUSIONS: Hyperhomocysteinemic patients on AEDs have
      indications of hypothyroidism, however, supplementation with B-vitamins does not
      improve their thyroid function.

PMID- 16466709
TI  - Distinct roles for ephrinB3 in the formation and function of hippocampal
      synapses.
AB  - The transmembrane ephrinB ligands and their Eph receptor tyrosine kinases are
      known to regulate excitatory synaptic functions in the hippocampus. In the CA3
      CA1 synapse, ephrinB ligands are localized to the post-synaptic membrane, while
      their cognate Eph receptors are presumed to be pre-synaptic. Interaction of
      ephrinB molecules with Eph receptors leads to changes in long-term potentiation
      (LTP), which has been reported to be mediated by reverse signaling into the post
      synaptic membrane. Here, we demonstrate that the cytoplasmic domain of ephrinB3
      and hence reverse signaling is not required for ephrinB dependent learning and
      memory tasks or for LTP of these synapses. Consistent with previous reports, we
      find that ephrinB3(KO) null mutant mice exhibit a striking reduction in CA3-CA1
      LTP that is associated with defective learning and memory tasks. We find the null
      mutants also show changes in both pre- and post-synaptic proteins including
      increased levels of synapsin and synaptobrevin and reduced levels of NMDA
      receptor subunits. These abnormalities are not observed in ephrinB3(lacZ) reverse
      signaling mutants that specifically delete the ephrinB3 intracellular region,
      supporting a cytoplasmic domain-independent forward signaling role for ephrinB3
      in these processes. We also find that both ephrinB3(KO) and ephrinB3(lacZ) mice
      show an increased number of excitatory synapses, demonstrating a cytoplasmic
      dependent reverse signaling role of ephrinB3 in regulating synapse number.
      Together, these data suggest that ephrinB3 may act like a receptor to transduce
      reverse signals to regulate the number of synapses formed in the hippocampus, and
      that it likely acts to stimulate forward signaling to modulate a number of other
      proteins involved in synaptic activity and learning/memory.

PMID- 16466710
TI  - Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes.
AB  - The nucleus of eukaryotic cells is organized into functionally specialized
      compartments that are essential for the control of gene expression, chromosome
      architecture and cellular differentiation. The mouse oocyte nucleus or germinal
      vesicle (GV) exhibits a unique chromatin configuration that is subject to dynamic
      modifications during oogenesis. This process of 'epigenetic maturation' is
      critical to confer the female gamete with meiotic as well as developmental
      competence. In spite of its biological significance, little is known concerning
      the cellular and molecular mechanisms regulating large-scale chromatin structure
      in mammalian oocytes. Here, recent findings that provide mechanistic insight into
      the complex relationship between large-scale chromatin structure and global
      transcriptional repression in pre-ovulatory oocytes will be discussed. Post
      translational modifications of histone proteins such as acetylation and
      methylation are crucial for heterochromatin formation and thus play a key role in
      remodeling the oocyte genome. This strategy involves multiple and hierarchical
      chromatin modifications that regulate nuclear dynamics in response to a
      developmentally programmed signal(s), presumably of paracrine origin, before the
      resumption of meiosis. Models for the experimental manipulation of large-scale
      chromatin structure in vivo and in vitro will be instrumental to determine the
      key cellular pathways and oocyte-derived factors involved in genome-wide
      chromatin modifications. Importantly, analysis of the functional differentiation
      of chromatin structure in the oocyte genome with high resolution and in real time
      will have wide-ranging implications to understand the role of nuclear
      organization in meiosis, the events of nuclear reprogramming and the spatio
      temporal regulation of gene expression during development and differentiation.

PMID- 16466711
TI  - Interleukin-4 improves the migration of human myogenic precursor cells in vitro
      and in vivo.
AB  - Different molecules are available to recruit new neighboring myogenic cells to
      the site of regeneration. Formerly called B cell stimulatory factor-1, IL-4 can
      now be included in the list of motogenic factors. The present report demonstrates
      that human IL-4 is not required for fusion between mononucleated myoblasts but is
      required for myotube maturation. In identifying IL-4 as a pro-migratory agent for
      myogenic cells, these results provide a mechanism which partly explains IL-4
      demonstrated activity during differentiation. Among the different mechanisms by
      which IL-4 might enhance myoblast migration processes, our results indicate that
      there are implications of some integrins and of three major components of the
      fibrinolytic system. Indeed, increases in the amount of active urokinase
      plasminogen activator and its receptor were observed following an IL-4 treatment,
      while the plasminogen activator inhibitor-1 decreased. Finally, IL-4 did not
      modify the amount of cell surface alpha5 integrin but increased the presence of
      beta3 and beta1 integrins. This integrin modulation might favor myogenic cell
      migration and its interaction with newly formed myotubes. Therefore, IL-4 co
      injection with transplanted myoblasts might be an approach to enhance the
      migration of transplanted cells for the treatment of a damaged myocardium or of a
      Duchenne Muscular Dystrophy patient.

PMID- 16466712
TI  - Functional analysis of the glaucoma-causing TIGR/myocilin protein: integrity of
      amino-terminal coiled-coil regions and olfactomedin homology domain is essential
      for extracellular adhesion and secretion.
AB  - TIGR/MYOC mutations account for 2-4% of the primary open-angle glaucoma (POAG)
      patients. More than 90% of the known mutations are located within its carboxy
      terminus olfactomedin-homology (Olf) domain (amino acids (aa) 245-504). In vitro
      and in vivo studies showed that several Olf domain mutations prevented myocilin
      secretion. To investigate if intracellular sequestration was a characteristic
      feature shared by a majority of the mutations, we analyzed the secretion status
      of 36 myocilin variants. These encompassed 26 glaucoma-causing mutations and 10
      non-disease associated or undefined polymorphisms. As several variants were found
      to be secreted, we tested for their adhesion to the extracellular matrix (ECM)
      and/or cell surface. Myocilin variants were generated by site-directed
      mutagenesis of a vector encoding the human MYOC cDNA. COS-7 or immortalized human
      trabecular meshwork cells were transfected with wild-type or mutated MYOC
      constructs. Myocilin levels were estimated by immunoprecipitation and/or
      immunoblotting. All variants showed identical behaviors in both cell lines; the
      truncated R46X polypeptide being the only variant which could not be detected in
      our assays. Of the 35 variants monitored, 20 remained sequestered
      intracellularly. All of them encoded disease-causing polypeptides carrying Olf
      domain mutations. Of the 15 variants secreted into the culture medium, six (6)
      were POAG mutants (of which three (3) located within the Olf domain) while the
      remaining nine (9) were non-disease causing or undefined polymorphisms. Three (3)
      of the six (6) secreted mutations caused familial POAG; these were the R126W,
      T377M and A427T mutants. Both, the T377M and A427T mutants located within the Olf
      domain. When cells were cultured at 30 degrees C, a process known to facilitate
      protein folding, 11 of the 20 sequestered mutants were released in the
      extracellular medium. Out of the 15 secreted variants tested for their adhesion
      to the ECM and/or cell surface, only the R82C and L95P polypeptides displayed
      loss of their adhesive properties. Deletion experiments revealed that the coiled
      coil (aa 78-105) and leucine zipper (aa 114-183) motifs were essential for
      adhesion. These experiments demonstrate that intracellular sequestration might be
      the primary mechanism contributing to myocilin-related POAG as it was associated
      with more than 80% of the disease-causing mutants tested in our study. A second
      mechanism may involve abnormal interaction(s) between myocilin and ECM and/or
      cell surface proteins. Our data further revealed the importance of the
      olfactomedin-homology domain for myocilin secretion and the significant role of
      the N-terminal region for its extracellular interactions.

PMID- 16466713
TI  - Rate of change in central corneal thickness: a viability indicator for
      conventional drainage tissues in organ culture.
AB  - Organ culture of human anterior segments is a powerful tool for understanding
      trabecular meshwork biology. However, data from a significant percentage of
      cultured anterior segments are unusable because tissues fail to meet quality
      control requirements, such as having adequate trabecular meshwork histology. The
      purpose of the present study was to evaluate a novel, real time method for
      assessing the viability of conventional drainage tissues in the human anterior
      segment perfusion model. Twenty-two human anterior segments were perfusion
      cultured using standard techniques for one week while measuring outflow facility
      and central corneal thickness (CCT). After perfusion-fixation, toludine blue
      stained histological sections of drainage tissues from all four quadrants of each
      anterior segment were graded and endothelial cell nuclei from cornea centers were
      stained with 4',6-diamidino-2-phenylindole and counted. We found that most
      anterior segments with a stable outflow facility had a CCT that decreased over
      time, while anterior segments with an unstable outflow facility had CCT
      measurements that failed to decrease over time (P<0.01). When comparing CCT
      measurements to histological appearance of outflow tissues, we found that in
      11/11 cases, anterior segments with an acceptable histological score had a
      negative CCT slope (P<0.01). Conversely in 3/4 instances, anterior segments with
      an unacceptable histological score had a positive CCT slope. Lastly, we observed
      a significant relationship between CCT measurements and corneal endothelial
      density (P<0.01). Thus, the simple procedure of measuring CCT during anterior
      segment perfusion provides a second useful measure to assess the viability of the
      anterior segment during the perfusion process.

PMID- 16466714
TI  - Comparison of invasive and non-invasive tonometry in the mouse.
AB  - Assessment of the accuracy of non-invasive rebound tonometry, and comparison with
      invasive cannulation tonometry. An in vivo calibration technique was devised to
      improve the accuracy of the rebound tonometer. IOP was then measured in SW mice
      using both rebound and cannulation tonometry. The ability of the rebound
      tonometer to accurately measure small IOP reductions after instillation of a
      topical prostaglandin was also determined. With the rebound method, mid-afternoon
      IOP in two groups of similar aged SW mice was 15.9+/-3.9 mmHg (mean+/-s.d., n=25)
      compared to 16.3+/-1.2 mmHg (n=32) using the cannulation technique. This
      difference was not statistically significant (p=0.6). For serial measurements
      using both techniques in the same eyes of a third group of SW mice (n=14), mean
      IOP was 15.0+/-3.9 mmHg for rebound tonometry but only 13.4+/-2.3 mmHg for
      subsequent cannulation tonometry. This effect was subsequently shown to be a
      consequence of the rebound tonometry, as multiple rebound measurements induced a
      statistically significant reduction in IOP. The average IOP reduction observed 2
      hr after a single application of topical latanoprost (200 ng) was 2.8+/-1.3 mmHg
      (p<0.001) and 2.4+/-4.7 mmHg (p=0.03) with cannulation and rebound tonometers,
      respectively. These differences were not significantly different (p=0.8). In vivo
      calibration of the rebound tonometer increased measurement accuracy and provided
      IOP values within the physiological range that agreed closely with the IOP
      measured by cannulation tonometry. However, IOP measurement with the rebound
      tonometer had larger variability compared with the cannulation method. Repeat IOP
      measurements with the rebound tonometer led to a reduction in IOP. The rebound
      tonometer was sufficiently sensitive to detect a 2-3 mmHg reduction in IOP
      following application of topical latanoprost. Despite these limitations, the
      rebound tonometer has a significant advantage over cannulation tonometry in that
      it permits longitudinal IOP measurement in conscious mice.

PMID- 16466715
TI  - Choroidal innervation and optic neuropathy in macacque monkeys with laser- or
      anterior chamber perfusion-induced short-term elevation of intraocular pressure.
AB  - Long-term intraocular pressure (IOP) elevation leads to a significant reduction
      of the intrinsic choroidal innervation and axon loss in the optic nerve. In this
      study we investigated early changes in these tissues in order to clarify the
      putative sequence of events between choroidal ganglion cell loss and optic nerve
      axon loss in 19 monkeys with experimentally induced glaucoma. After 1 month of
      increased IOP, severe optic neuropathy but no reduction of choroidal ganglion
      cells (CGC) was detectable. Beginning at 2 months after treatment signs of
      degeneration in CGC morphology were observed. Laser treatment of the trabecular
      meshwork without IOP elevation caused no changes in choroidal innervation. Our
      results show that there is no apparent association between reduction of CGC and
      optic neuropathy in the early stages of IOP elevation.

PMID- 16466717
TI  - Roles of cAMP in regulating microtubule sliding and flagellar bending in
      demembranated hamster spermatozoa.
AB  - To understand the mechanism regulating spermatozoa motility, it is important to
      investigate the mechanism regulating the conversion of microtubule sliding into
      flagellar bending. Therefore, we analyzed microtubule sliding and its conversion
      into flagellar bending using a demembranated spermatozoa model in which
      microtubule sliding and flagellar bending could be analyzed separately by
      treating the demembranated spermatozoa with and without dithiothreitol,
      respectively. Using this model, we examined the roles of cAMP and its target
      molecules in regulating flagellar bending and microtubule sliding. Although
      flagellar bending did not occur in the absence of cAMP, microtubule extrusion
      occurred without it, suggesting that cAMP is necessary for the conversion of
      microtubule sliding into flagellar bending, but not for microtubule sliding
      itself. The target of cAMP for regulating flagellar bending was not cAMP
      dependent protein kinase (PKA), since flagellar bending was still observed in the
      spermatozoa treated with a PKA-specific inhibitor. Alternatively, the Epac/Rap
      pathway may be the target. Epac2 and Rap2 were detected in hamster spermatozoa
      using immunoblotting. Since Rap2 is a GTPase, we investigated the flagellar
      bending of demembranated spermatozoa treated with GTPgammaS. The treatment
      markedly increased the beat frequency and bending rate. These results suggest
      that cAMP activates the Epac/Rap pathway to regulate the conversion of
      microtubule sliding into flagellar bending.

PMID- 16466716
TI  - The effect of temperature on gene silencing by siRNAs: implications for silencing
      in the anterior chamber of the eye.
AB  - Gene silencing by siRNAs offers the potential for reducing the expression of
      mutated genes that cause disease. It has been shown that the folding or secondary
      structure of a specific mRNA was significantly correlated to the silencing
      observed. Since this base pairing is dependent on free energy, the temperature of
      the cells may influence the effectiveness of a particular siRNA. The aqueous
      humor of the human eye has been measured to be around 34 degrees C with the lens
      acting as a thermal barrier in the eye. The trabecular meshwork, bathed by the
      aqueous humor, probably has a temperature lower than body temperature under
      normal conditions. Mutated myocilin, that is associated with primary open angle
      glaucoma, would appear to be a candidate for silencing by siRNAs. Silencing of
      the mutated myocilin might prevent additional accumulation of this protein in the
      rough endoplasmic reticulum. These experiments were undertaken to determine the
      influence of lowered temperatures on the silencing of myocilin by five siRNAs.
      Three different patterns of silencing emerged when the silencings were compared
      with cells grown at 33, 35, and 37 degrees C. For one of the siRNAs, the
      silencing was increased at lower temperatures. For two siRNAs, no significant
      changes in silencing were observed with different temperatures. Two of the siRNAs
      were significantly influenced by temperature with little if any silencing
      occurring at the lowest temperature. These data indicate that siRNAs directed to
      tissues in the anterior chamber of the eye should be checked at temperatures
      lower than 37 degrees C to determine their effectiveness.

PMID- 16466719
TI  - Characterization of the cysteine protease domain of Semliki Forest virus
      replicase protein nsP2 by in vitro mutagenesis.
AB  - The function of Semliki Forest Virus nsP2 protease was investigated by site
      directed mutagenesis. Mutations were introduced in its protease domain, Pro39,
      and the mutated proteins were expressed in Escherichia coli, purified and their
      activity in vitro was compared to that of the wild type Pro39. Mutations M781T,
      A662T and G577R, found in temperature-sensitive virus strains, rendered the
      enzyme temperature-sensitive in vitro as well. Five conserved residues were
      required for the proteolytic activity of Pro39. Changes affecting Cys478, His548,
      and Trp549 resulted in complete inactivation of the enzyme, whereas the
      replacements N600D and N605D significantly impaired its activity. The importance
      of Trp549 for the proteolytic cleavage specificity is discussed and a new
      structural motif involved in substrate recognition by cysteine proteases is
      proposed.

PMID- 16466718
TI  - hPTH-fragments (53-84) and (28-48) antagonize the stimulation of calcium release
      and repression of alkaline phosphatase activity by hPTH-(1-34) in vitro.
AB  - Different C-terminal fragments of parathyroid hormone (PTH)-(1-84) in blood
      participate in the regulation of calcium homeostasis by PTH-(1-84), and an
      antagonizing effect for the large carboxyl-terminal parathyroid hormone (C-PTH)
      fragment (7-84) on calcium release has been described in vivo and in vitro. In
      this study the smaller C-PTH-fragment (53-84) and mid-regional PTH fragment (28
      48), which represent discrete areas of activity in the PTH-(7-84) molecule, were
      assayed for their effects on calcium release and alkaline phosphatase (ALP)
      activity in a chick bone organ culture system. Neither PTH-(28-48) nor PTH-(53
      84) had any effect on calcium release into the medium and both fragments
      stimulated ALP activity in the bone tissue, suggesting that the cAMP/PKA
      signalling pathway was not affected by these fragments. However they suppressed
      the calcium release induced by PTH-(1-34) and attenuated the down regulation of
      ALP activity caused by PTH-(1-34), suggesting that the effect on the cAMP/PKA
      signalling pathway may be indirectly. In conclusion, the study shows that the PTH
      fragments (53-84) and (28-48) antagonize the PTH-(1-34) induced effects on
      calcium release and inhibition of ALP activity in a chick bone organ culture
      system.

PMID- 16466720
TI  - Gln(84) of moloney murine leukemia virus reverse transcriptase regulates the
      incorporation rates of ribonucleotides and deoxyribonucleotides.
AB  - Moloney murine leukemia virus reverse transcriptase (RT) selectively uses
      deoxyribonucleotides over ribonucleotides (rNTPs) as substrates. Substitution of
      F155 with valine (F155V) was previously found to increase the enzyme's affinity
      for rNTPs, though without affecting the V(max) for catalysis, and thereby
      conferred to the enzyme significant RNA polymerase activity. We have sought new
      mutations that might increase the RNA polymerase activity of the F155V mutant. We
      report here that substitution of Q84 with alanine improved RT-F155V's RNA
      polymerase activity, but also its DNA polymerase activity. Kinetic analysis and
      gel-retardation assays suggested that the substitution increased the enzyme's
      general affinity for the template-primer.

PMID- 16466721
TI  - Conserved cis-elements in the Xenopus red opsin promoter necessary for cone
      specific expression.
AB  - The long-wavelength sensitive (red) opsin genes encode proteins which play a
      central role in daytime and color vision in vertebrates. We used transgenic
      Xenopus to identify 5' cis-elements in the red cone opsin promoter necessary for
      cone-specific expression. We found a highly conserved extended region (-725 to 
      173) that was required for restricting GFP transgene expression to cones. We
      further identified a short element (5'-CCAATTAAGAGAT-3') highly conserved amongst
      tetrapods, including humans, necessary to restrict expression to cones in the
      retina. These results identify novel conserved elements that regulate spatial
      expression of tetrapod red cone opsin genes.

PMID- 16466722
TI  - A tyrosine residue deprotonates during oxygen reduction by the caa3 reductase
      from Rhodothermus marinus.
AB  - Heme-copper oxygen reductases catalyze proton translocation across the cellular
      membrane; this takes place during the reaction of oxygen to water. We demonstrate
      with attenuated total reflection-Fourier transform infrared (ATR-FTIR) difference
      spectroscopy that a tyrosine residue of the oxygen reductase from the
      thermohalophilic Rhodothermus marinus becomes deprotonated in the transition from
      the oxidized state to the catalytic intermediate ferryl state P(M). This tyrosine
      residue is most probably Y256, the helix VI tyrosine residue proposed to
      substitute for the D-channel glutamic acid that is absent in this enzyme.
      Comparison with the mitochondrial like oxygen reductase from Rhodobacter
      sphaeroides suggests that proton transfer from a strategically situated donor to
      the active site is a crucial step in the reaction mechanism of oxygen reductases.

PMID- 16466723
TI  - Long inverted repeats in eukaryotic genomes: recombinogenic motifs determine
      genomic plasticity.
AB  - Inverted repeats are unstable motifs in a genome, having a causal relation to
      fragment rearrangements and recombination events. We have investigated long
      inverted repeats (LIR) of > 30 bp in length in eukaryotic genomes to assess their
      contribution to genome stability. An algorithm was first designed for searching
      for LIRs with < 2 kb internal spacers and >85% identity (degree of homology
      between repeat copies of a LIR). There are much fewer LIRs in yeast, fruitfly,
      pufferfish and chicken than in Caenorhabditis elegans, zebrafish, frog and human.
      However, the high LIR frequencies do not necessarily imply high genome
      instability because of variant internal spacers and stem lengths and identities.
      From the collection of identified LIRs, we selected recombinogenic LIRs that had
      a short internal spacer and a high copy identity and were prone to induce high
      instability. We found that a relatively high proportion (5-9.8%) of the LIRs in
      C. elegans, zebrafish and frog were recombinogenic LIRs. In contrast, the
      proportions in human and mouse LIRs were quite low (0.4-1.1%) basically
      accounting for long internal spacers. We suggest that C. elegans, zebrafish and
      frog genomes are unstable in terms of the LIR frequency and the proportion of
      recombinogenic LIRs. For the other genomes, LIRs most likely have a minor impact.

PMID- 16466724
TI  - ACTH cells of pituitary pars distalis of viscacha (Lagostomus maximus maximus):
      immunohistochemical study in relation to season, sex, and growth.
AB  - Corticotrope or ACTH cells were immunohistochemically identified in the pituitary
      pars distalis (PD) of viscacha by using the polyclonal antiserum against ACTH (1
      24). The localization, distribution, shape, percentage immunopositive area, and
      major cellular and nuclear diameters of these cells were analyzed by image
      analysis in adult male viscachas captured in their natural habitat during the
      year and after the chronic administration of melatonin. The same parameters were
      analyzed in immature male and adult female viscachas. ACTH cells in adult males
      were mainly localized in the dorsal and cephalic regions of PD. They were
      isolated, forming small groups and in contact with follicular structures and
      blood vessels. They were pleomorphic, with some of them being polygonal, oval,
      round, and others, stellate with cytoplasmic extensions. The percentage
      immunopositive area and the major cellular diameter showed seasonal variations
      with lower values during June and July (early winter). A decrease in the
      percentage immunopositive area was observed after the administration of melatonin
      in adult male animals. ACTH cells of immature animals differed from the adults'
      cells in their distribution, shape, pattern of immunolabeling, and percentage
      immunopositive area. These parameters in adult females did not vary in relation
      to adult males at the same time of the year although. However, the cells in
      females were smaller in size during April-May. In pregnant viscachas (June-July),
      these parameters did not show significant differences with the results of non
      pregnant females (April-May). This suggests that the environmental stressors do
      not exert the same influence on the hypothalamo-pituitary-adrenal axis in adult
      male and female viscachas, probably due to the physiological changes caused by
      pregnancy. Our results in adult male viscacha demonstrate that the morphology of
      the ACTH cells varies according to the different seasonal conditions, thus
      participating in the adaptation process of this rodent to the environment. The
      elevated levels of melatonin during winter months might inhibit the synthesis of
      ACTH, probably when affecting some secretagogue of this pituitary hormone.
      Moreover, the morphological variations observed between adult and immature male
      viscachas and between both sexes suggest that the steroid gonadal hormones might
      act on the development and activity of ACTH cells.

PMID- 16466725
TI  - Thyroid hormone profile during annual reproductive cycle of diploid and triploid
      catfish, Heteropneustes fossilis (Bloch).
AB  - Triploid fishes generally show sterility along with retarded gonadal development
      and aneuploid gametes. In teleosts, thyroid hormones influence seasonal
      adaptations and annual events such as reproduction. In addition, thyroid hormone
      deposition in matured ova is important for reproductive success as the role of
      thyroid hormones in early development and metamorphosis is well established. The
      present study deals with measurements of free and total thyroxine (T4) and
      triiodothyronine (T3) in the plasma of triploid and diploid catfish
      Heteropneustes fossilis (Bloch) in a complete reproductive cycle. Accumulations
      of total T4 and T3 within the oocytes have also been measured during the spawning
      period from fishes of both ploidy groups. No difference of plasma free hormones
      was noticed between the diploids and triploids of both the sexes in any period of
      reproductive cycle, although, seasonal variations were noted in both the groups.
      A significant decrease in the total thyroid hormone levels was noticed in plasma
      of the diploids in the spawning period compared to triploid fish. During the same
      period, accumulation of THs was significantly higher in the oocytes of diploids
      than that of the triploids. Thyroid gland structure also revealed a higher state
      of activity in the female diploids than the triploids during spawning period.
      Lower activity of thyroid tissue, higher levels of THs in plasma, and lower
      accumulation of maternally derived hormones in the oocytes of triploid females
      during spawning period may be associated with sterility of triploids.

PMID- 16466726
TI  - Hyperthermia induced atrial natriuretic peptide expression and deviant heart
      development in Atlantic salmon Salmo salar embryos.
AB  - Heart abnormalities are increasingly recognized as a problem in salmon
      aquaculture. Fish in early life-stages are particularly susceptible to
      teratogens, including elevated water temperature. Recently, heat-induced mRNA
      expression of the cardiac hormone atrial natriuretic peptide (ANP), which is
      known to be involved in modulation of cardiac growth and regulation of cardiac
      homeostasis, was demonstrated in Atlantic salmon (Salmo salar) embryos by RAP
      PCR. The relation between heat sensitive ANP expression and heart abnormalities
      was explored in two experiments. In an experiment with short-term exposure,
      salmon eggs were heat shocked at 16 degrees C at eight different embryonic stages
      from gastrulation till completion of somitogenesis. The RT-PCR results showed
      that the ANP mRNA expression was down-regulated at the onset of heart formation
      at the gastrula stage, while the transcription became heat inducible from the
      fusioning of the heart tube around the 15th-20th somite stage and onwards. This
      was confirmed by whole-mount in situ hybridization, which also showed that ANP is
      exclusively expressed in the heart of Atlantic salmon embryos. In a second long
      term experiment, salmon embryos were incubated at either 10 degrees C (high
      temperature) or 8 degrees C (controls) from fertilization till first feeding, and
      subsequently reared within normal conditions to an average size of 52 g. The long
      term hyperthermic embryos showed up-regulated ANP transcription at the
      approximately 9th and approximately 20th somite stage and at the completion of
      somitogenesis. The cardiosomatic index [CSI; (ventricle weight/body weight) *100]
      demonstrated a significant decrease in the relative heart weight of fish
      incubated at 10 degrees C during the embryogenesis compared with controls. In
      these fish, aplasia of septum transversum was observed in 2 of 25 fish, resulting
      in abnormally shaped hearts situated partly within the abdominal cavity.
      Altogether, our results demonstrate that hyperthermia both induce deviant
      development of heart and associated structures and up-regulation of ANP
      transcription during embryogenesis. A possible role of ANP in development of
      heart malformations is thus suggested.

PMID- 16466727
TI  - Effects of methoprene, nonylphenol, and estrone on the vitellogenesis of the
      mysid Neomysis integer.
AB  - The induction of the female-specific protein, vitellogenin, in male fish is a
      well-established endpoint to assess exposure to estrogen-like chemicals. The use
      of vitellogenesis as a biomarker for xenobiotic exposure in egg-laying
      invertebrates, however, is still relatively unexplored. Recently, we developed a
      quantitative enzyme-linked immunosorbent assay (ELISA) for vitellin in Neomysis
      integer (Crustacea: Mysidacea) to study mysid vitellogenesis and its potential
      disruption by xenobiotics. In this study, gravid mysids were exposed to
      methoprene, nonylphenol, and estrone for 96 h. All methoprene-exposed (0.01, 1,
      and 100 microg/L) animals had lower vitellin levels compared to the control
      animals, though this effect was not statistically significant. Exposure to
      nonylphenol resulted in significantly induced vitellin levels in the lowest
      exposure concentration (0.01 microg/L), whereas no effects were observed at
      higher concentrations. Estrone significantly decreased vitellin levels at the
      highest test concentration (1 microg/L). These results indicate that mysid
      vitellogenesis can be disrupted following chemical exposure. Difficulties in the
      interpretation of the observed chemical-specific and concentration-specific
      responses in this study highlight the need for a better understanding of hormone
      regulation of crustacean vitellogenesis.

PMID- 16466728
TI  - Soluble Fas, a mediator of apoptosis, C-reactive protein, and coronary and
      extracoronary atherosclerosis. The Rotterdam Coronary Calcification Study.
AB  - RATIONALE: Findings from laboratory studies strongly suggest a role for
      apoptosis, the process of programmed cell death, in cardiovascular disease. No
      population-based study has yet investigated whether serum levels of soluble forms
      of Fas, a receptor capable of inducing the apoptosis cascade, are associated with
      coronary and extracoronary atherosclerosis. METHODS: Within the Rotterdam
      Coronary Calcification Study, a population-based cohort study, we measured
      coronary calcification using electron-beam computed tomography, abdominal aortic
      calcification by abdominal X-ray, carotid plaques and common carotid intima-media
      thickness (IMT) by ultrasonography, and lower extremity atherosclerosis by
      computation of the ankle-arm index. Levels of sFas and of the inflammatory
      mediator C-reactive protein (CRP) were measured in 1036 participants. RESULTS:
      Levels of sFas were not related to coronary or extracoronary atherosclerosis. CRP
      showed strong associations with measures of atherosclerosis, including coronary
      atherosclerosis, which largely remained after adjustment for traditional
      cardiovascular risk factors. CONCLUSION: The results of this study do not support
      a role for sFas in the identification of subjects with atherosclerosis.

PMID- 16466729
TI  - Marked changes in plasma lipids and lipoproteins during pregnancy in women with
      familial hypercholesterolemia.
AB  - Serum lipids increase during pregnancy. However, data are scarce for lipid
      changes in pregnant women with heterozygous familiar hypercholesterolemia (FH).
      The purpose of the present study was to examine plasma lipids and lipoproteins
      during pregnancy in women with FH. In 22 pregnant women blood samples were
      collected at gestational weeks 17-20 (baseline), 24, 30 and 36. Total- and LDL
      cholesterol increased significantly between baseline and gestational week 36 by
      29% and 30%, respectively, compared to 25% and 34% in a reference group of 149
      healthy pregnant women. Notably, the plasma lipid concentrations in the FH women
      were much higher than in the reference women. Triglycerides increased (P<0.05) by
      116% and 103%, in the FH group and reference group, respectively. HDL cholesterol
      was unchanged in both groups. Moreover, apolipoprotein B increased significantly
      during pregnancy in the FH women, whereas apolipoprotein A1 and lipoprotein (a)
      were unchanged. Pregnancy outcomes in the FH group did not differ significantly
      from those in the reference group. In conclusion, the relative increase in plasma
      lipids was similar in pregnant women with FH and in healthy women, but the
      absolute magnitude was considerably larger in pregnant FH women.

PMID- 16466730
TI  - The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of
      plasma lipids among familial hypercholesterolaemia patients.
AB  - BACKGROUND AND AIM: Hypercholesterolaemia is a major risk factor for
      atherosclerosis. Cholesterol is modulated by genetic and environmental factors.
      An important regulatory pathway is controlled by the sterol-regulatory element
      binding proteins (SREBPs) and the SREBP cleavage-activating protein (SCAP). Both
      SREBP-2 and SCAP are candidates to contribute to the development of
      atherosclerosis. We investigated the possible effects of the variability of
      proteins involved in this regulatory pathway on plasma lipids among familial
      hypercholesterolaemia patients. METHODS AND RESULTS: Single nucleotide
      polymorphisms (SNPs) in the genes encoding SREBP-2 and SCAP causing amino acid
      changes at positions 595 (595G/A) and 796 (796I/V), respectively, were genotyped
      in 801 FH individuals originating from Israel, The Netherlands, and Switzerland.
      A linear regression model to examine the associations between SREBP-2 and SCAP
      isoforms and lipid and lipoprotein levels was used. In females, homozygosity
      either for the SREBP-2-595A or for the SCAP-796I isoform was associated with
      higher LDL-cholesterol plasma concentrations (14.7 mg/dl and 20.3 mg/dl,
      respectively). Surprisingly, heterozygosity for the combination SREBP-2-595A/SCAP
      796I was associated with a decrease of 30.28 mg/dl in LDL-C (p-value for gene
      gene interaction=0.09). No such effect was observed among FH males. Subgroup
      analysis considering the most frequent (N>/=24) LDL receptor mutations (del191-2,
      ins313+1-2, C660X, E207K, S285L) revealed further gene-dosage- and gender
      dependent effects of the SCAP mutations on LDL-cholesterol concentrations
      (p=0.0345). These effects were, however, not present when less frequent LDL
      receptor mutations were investigated. CONCLUSIONS: These results suggest a
      possible gene-gene interaction between the genes encoding SREBP-2 and SCAP that
      modulate plasma lipids in a strictly gender-specific fashion. Further
      investigation is needed to confirm this effect. A study in a larger FH group or
      in non-FH hypercholesterolaemic subjects may further define the role of this
      regulatory mechanism in determining plasma lipid concentration.

PMID- 16466731
TI  - Continuous spin fractionation and characterization by size-exclusion
      chromatography for styrene-butadiene block copolymers.
AB  - Linear and star-shaped styrene-butadiene block copolymers synthesized by anionic
      polymerization of butadiene and styrene were fractionated by applying a newly
      developed large-scale fractionation technique, named continuous spin
      fractionation (CSF). Their molecular weight and polydispersity index
      (d=M(w)/M(n)) were measured with size-exclusion chromatography and static light
      scattering. For the linear triblock copolymer a fractionation via temperature
      variation turned out to be better suited than the usual isothermal procedure. The
      star-shaped polymer with the d value of 1.33 was fractionated in two CSF steps to
      get the targeted sample, which has a considerably more uniform structure and a
      narrower molecular weight distribution (d=1.11). The corresponding starting
      linear diblock copolymer was fractionated in one step reducing d from 1.68 to
      1.17. With one set of simple laboratory equipment, 1kg polymer can be
      fractionated per day. Utilizing CSF, for the first time, we fractionated
      successfully the block copolymers.

PMID- 16466732
TI  - Determination of estradiol and its degradation products by liquid chromatography.
AB  - A novel HPLC method for simultaneous determination of estradiol and its seven
      degradation products in topical gel was developed. Zorbax SB-CN (150 mm x 4.6 mm,
      5 microm) analytical column and mobile phase composed of acetonitrile, phosphoric
      acid 0.085%, and tetrahydrofurane (27:63:10, v/v/v) at flow-rate 1.0 ml min(-1)
      were used for the chromatographic separation using UV detection at 225 nm. The
      active substance estradiol was separated from all its known degradation products
      successfully. Two degradation products estrone and Delta(9(11))-estrone were not
      separated sufficiently, their peaks were evaluated as a sum of two components.
      The method was validated according to ICH guideline recommendations and
      thereafter it was successfully applied for stability tests of topical cream
      Estrogel HBF in the quality control laboratory. Limits of detection for
      degradation products ranged from 1.03 x 10(-5) to 1.14 x 10(-4) mg ml(-1), limits
      of quantitation for degradation products were in the range 3.43 x 10(-5) to 3.81
      x 10(-4) mg ml(-1). The developed method is selective, precise, accurate and
      sensitive enough for determination of estradiol and its known degradation
      products.

PMID- 16466734
TI  - Development and application of a high-performance liquid chromatography method
      using monolithic columns for the analysis of ecstasy tablets.
AB  - A rapid and selective HPLC method using monolithic columns was developed for the
      separation and quantification of the principal amphetamines in ecstasy tablets.
      Three monolithic (Chromolith RP18e) columns of different lengths (25, 50 and 100
      mm) were assessed. Validation studies including linearity, selectivity,
      precision, accuracy and limit of detection and quantification were carried out
      using the Chromolith SpeedROD, RP-18e, 50 mm x 4.6 mm column. Column backpressure
      and van Deemter plots demonstrated that monolithic columns provide higher
      efficiency at higher flow rates when compared to particulate columns without the
      loss of peak resolution. Application of the monolithic column to a large number
      of ecstasy tablets seized in Ireland ensured its suitability for the routine
      analysis of ecstasy tablets.

PMID- 16466733
TI  - High-performance liquid-chromatographic determination of 5-aminosalicylic acid
      and its metabolites in blood plasma.
AB  - Mesalazine (5-aminosalicylic acid, 5-ASA), an anti-inflammatory agent for the
      treatment of inflammatory bowel diseases, is metabolized in organism to the
      principal biotransformation product, N-acetyl-5-ASA. Some other phase II
      metabolites (N-formyl-5-ASA, N-butyryl-5-ASA, N-beta-d-glucopyranosyl-5-ASA) have
      also been described. 5-ASA is a polar compound and besides it exhibits amphoteric
      properties. The extraction of this compound from biomatrices and its
      chromatographic analysis is complicated. In order to improve the reliability of
      the determination of parent 5-ASA, a derivatization of 5-ASA together with 4-ASA
      (added to samples as a precursor of I.S.-2) was involved into the method. More
      lipophilic N-propionyl-5-ASA and N-propionyl-4-ASA (I.S.-2) were obtained using
      propionic anhydride. These derivatives were well extractable together with N-acyl
      5-ASAs (metabolites) and N-acetyl-4-ASA (I.S.-1). As the first internal standard
      (I.S.-1) was used for the evaluation of extracted N-acyl-metabolites, the second
      internal standard (I.S.-2) served for the evaluation of both derivatization and
      extraction steps of parent drug 5-ASA. Based on these reasonings, new HPLC
      bioanalytical method for the determination of 5-ASA and its metabolites in blood
      plasma was developed and validated. The sample preparation step consists of the
      deproteination of plasma by HClO(4) and the above-mentioned derivatization of
      ASAs followed by liquid-liquid extraction of all N-acyl-ASA-derivatives.
      Chromatographic analyses were performed on a 250-4 mm column containing Purospher
      RP-18 e, 5 microm (Merck, Darmstadt, Germany) with a precolumn (4-4 mm). The
      column effluent was monitored using both UV photodiode-array (lambda = 313 nm)
      and fluorescence detectors (lambda(exc.) = 300 nm/lambda(emiss.) = 406 nm) in
      tandem. The identity of individual N-acyl-ASAs in the extracts from biomatrices
      was verified by characteristic UV-spectra and by HPLC/MS experiments. The whole
      analysis lasted 23 min at the flow rate of 1 ml min(-1). LLOQ (LOD) was estimated
      126 (20) pmol ml(-1) of plasma for N-acetyl-5-ASA and 318 (50) pmol ml(-1) of
      plasma for N-propionyl-5-ASA. The validated HPLC method was applied to
      pharmacokinetic studies of mesalazine in humans and animals.

PMID- 16466735
TI  - pH-dependent surface charging and points of zero charge. III. Update.
AB  - The recently published points of zero charge (PZC) of various materials are
      compiled to update previous compilations [M. Kosmulski, Chemical Properties of
      Material Surfaces, Dekker, New York, 2001; M. Kosmulski, J. Colloid Interface
      Sci. 253 (2002) 77; M. Kosmulski, J. Colloid Interface Sci. 275 (2004) 214]. The
      recent results corroborate the previously found PZC with a few exceptions. The
      PZC of alumina obtained from the second-harmonic generation response is
      substantially lower than the PZC obtained by means of standard methods, while for
      titania the difference is less significant. PZC of Tl2O3 at pH 7.9 was reported
      for the first time. A surprisingly insignificant temperature effect on the IEP of
      rutile was found. Recent model studies aimed at explanation of the effect of the
      nature of 1-1 electrolytes on the course of charging curves and of discrepancies
      in the PZC of different materials having the same chemical formula are
      summarized.

PMID- 16466736
TI  - The impact of Mn oxide coatings on Zn distribution.
AB  - Zinc sorption to hydrous manganese oxide (HMO)-coated clay was investigated
      macroscopically, kinetically, and spectroscopically. Adsorption edges and
      isotherms revealed that the affinity and capacity of the HMO-coated
      montmorillonite was greater than that of montmorillonite, and when normalized to
      the oxide present, the coatings behaved similarly to the discrete Mn oxide. Over
      two pH conditions, 5 and 6, a linear relationship was observed for the isotherms;
      further analysis with X-ray absorption spectroscopy (XAS) resulted in one type of
      sorption configuration as a function of loading and ionic strength at pH 5.
      However, at a surface loading of 10(-3) mol(Zn) g(HMO-coatedclay)(-1) when the pH
      increased from 5 to 7, the first shell distance decreased slightly, while the
      atoms and coordination numbers remained the same; this change may be attributed
      to an increase in electrostatic interactions. After a contact time of 4 months
      where an additional 60% of the sites become occupied, the slower sorption process
      was modeled as intraparticle surface diffusion. Best fit diffusivities ranged
      from 10(-18) to 10(-17) cm2/s, where a slower process was observed for the coated
      surface as compared to the discrete oxide. Interestingly, the porosity of the Mn
      oxide coating appears to be influenced by the substrate during its growth, as its
      increase and shift to a smaller pore size distribution resulted in a diffusivity
      between that observed for discrete HMO and montmorillonite.

PMID- 16466737
TI  - Detection of PrP(Sc) in rectal biopsy and necropsy samples from sheep with
      experimental scrapie.
AB  - Scrapie diagnosis is based on the demonstration of disease-associated prion
      protein (PrP(Sc)) in brain or, in the live animal, in readily accessible
      peripheral lymphoid tissue. Lymphatic tissues present at the rectoanal line were
      readily obtained from sheep without the need for anaesthesia. The presence of
      PrP(Sc) in such tissue was investigated in sheep infected orally with scrapie
      infected brain material. The methods used consisted of immunohistochemistry and
      histoblotting on biopsy and post-mortem material. PrP(Sc) was detected in animals
      with PrP genotypes associated with high susceptibility to scrapie from 10 months
      after infection, i.e., from about the time of appearance of early clinical signs.
      In the rectal mucosa, PrP(Sc) was found in lymphoid follicles and in cells
      scattered in the lamina propria, often near and sometimes in the crypt
      epithelium. By Western blotting, PrP(Sc) was detected in rectal biopsy samples of
      sheep with the PrP genotype VRQ/VRQ, after electrophoresis of material equivalent
      to 8 mg of tissue. This study indicated that rectal biopsy samples should prove
      useful for the diagnosis of scrapie in sheep.

PMID- 16466738
TI  - Gas exchange characteristics, metabolic rate and water loss of the Heelwalker,
      Karoophasma biedouwensis (Mantophasmatodea: Austrophasmatidae).
AB  - This study presents the first physiological information for a member of the
      wingless Mantophasmatodea, or Heelwalkers. This species shows cyclic gas exchange
      with no evidence of a Flutter period (more typical of discontinuous gas exchange
      in insects) and no indication that the spiracles are fully occluded during
      quiescent metabolism. Standard metabolic rate at 20 degrees C was 21.32+/-2.73
      microl CO(2)h(-1) (mean+/-S.E.), with a Q(10) (10-25 degrees C) of 1.7. Increases
      in V()CO(2) associated with variation in mass and with trial temperature were
      modulated by an increase in burst period volume and a decline in cycle frequency.
      Total water loss rate, determined by infrared gas analysis, was 0.876+/-0.08 mg
      H(2)Oh(-1) (range 0.602-1.577, n=11) whilst cuticular water loss rate, estimated
      by linear regression of total water loss rate and metabolic rate, was 0.618+/
      0.09 mg H(2)Oh(-1) (range 0.341-1.363, n=11). Respiratory water loss rate was
      therefore no more than 29% of the total rate of water loss. Both total water loss
      rate and estimated cuticular water loss rate were significantly repeatable, with
      intraclass correlation coefficients of 0.745 and 0.553, respectively.

PMID- 16466739
TI  - Noncanonical cAMP pathway and p38 MAPK mediate beta2-adrenergic receptor-induced
      IL-6 production in neonatal mouse cardiac fibroblasts.
AB  - We previously reported that cardiac fibroblasts, but not cardiomyocytes, are
      served as the predominant source of IL-6 after isoproterenol stimulation in mouse
      myocardium. The present study investigated the molecular mechanism of
      isoproterenol-mediated secretion of IL-6 in mouse cardiac fibroblasts. Treatment
      of cells with isoproterenol-induced a time-dependent accumulation of IL-6, which
      was mediated by beta(2)-adrenergic receptor (AR), the preponderant beta-AR
      subtype in cardiac fibroblasts. Isoproterenol-induced secretion of IL-6 was
      mainly mediated by Gs-AC-cAMP signaling cascade and could be negatively regulated
      by Gi and PI3K. Surprisingly, the effect of cAMP was independent of protein
      kinase A and the exchange protein directly activated by cAMP (Epac)-Rap1 pathway
      and suggests the existence of a novel cAMP-dependent mechanism. p38 MAPK
      inhibitor SB203580, but not extracellular regulated protein kinase inhibitor,
      abrogated isoproterenol-induced IL-6 release in cardiac fibroblasts and mouse
      myocardium. Interestingly, p38 MAPK could also be positively regulated by Gs-AC
      cAMP but negatively regulated by Gi-PI3K pathway. Finally, multiple transcription
      factors (AP-1, C/EBP, NF-kappaB and CREB) regulating the IL-6 gene are activated
      in response to isoproterenol stimulation, which may provide essential linkage
      between upstream cAMP-p38 MAPK signaling cascade and downstream IL-6 gene
      transcription. The present results suggest that beta(2)-AR mediates IL-6
      production through a noncanonical cAMP responsible pathway and p38 MAPK.

PMID- 16466740
TI  - Galphaq expression activates EGFR and induces Akt mediated cardiomyocyte
      survival: dissociation from Galphaq mediated hypertrophy.
AB  - Our laboratory has previously shown that adenoviral-mediated overexpression of
      Galphaq in neonatal rat ventricular cardiomyocytes increases the phosphorylation
      of Akt, a well-established anti-apoptotic effector. As demonstrated here, Galphaq
      expression protects cardiomyocytes against apoptosis induced by treatment with 2
      deoxyglucose (2DOG) and this protection is lost when Akt activation is prevented
      by treatment with LY294002 (an inhibitor of PI3K). Galphaq-induced Akt
      phosphorylation is not caused by increased Gbetagamma signaling and does not
      appear to involve PKC activation. Rather studies using the EGF receptor inhibitor
      AG1478 and the Src inhibitor PP2 implicate these tyrosine kinases in the pathway
      inducing Akt phosphorylation. EGFR phosphorylation is increased in cells
      expressing Galphaq and this effect is inhibited by PP2, placing Src upstream of
      EGFR phosphorylation. EGFR activation appears to be required for Galphaq-mediated
      protection since inhibition of Src or EGFR rendered cells susceptible to 2DOG
      induced apoptosis. In contrast to the requirement for EGFR mediated Akt
      activation in cardioprotection, neither EGFR nor Akt activation are necessary for
      the hypertrophic increases in cell size or ANF content elicited by Galphaq
      overexpression. These data demonstrate that increased Galphaq activity can
      provide anti-apoptotic signals by eliciting EGFR phosphorylation and subsequent
      Akt activation, independent of the well-known ability of Galphaq signaling to
      elicit hypertrophy.

PMID- 16466741
TI  - Amyloid formation by recombinant full-length prion proteins in phospholipid
      bicelle solutions.
AB  - A soluble, oligomeric beta-sheet-rich conformational variant of recombinant full
      length prion protein, PrP beta, was generated that aggregates into amyloid
      fibrils, PrP betaf. These fibrils have physico-chemical and structural properties
      closely similar to those of pathogenic PrP Sc in scrapie-associated fibrils and
      prion rods, including a closely similar proteinase K digestion pattern and Congo
      red birefringence. The conformational transition from PrP C to PrP beta occurs at
      pH 5.0 in bicellar solutions containing equimolar mixtures of dihexanoyl
      phosphocholine and dimyristoyl-phospholipids, and a small percentage of
      negatively charged dimyristoyl-phosphoserine. The same protocol was applicable to
      human, cow, elk, pig, dog and mouse PrP. Comparison of full-length hPrP 23-230
      with the N-terminally truncated human PrP fragments hPrP 90-230, hPrP 96-230,
      hPrP 105-230 and hPrP 121-230 showed that the flexible peptide segment 105-120
      must be present for the generation of PrP beta. Dimerization of PrP C represents
      the rate-limiting step of the PrP C-to-PrP beta conformational transition, which
      is dependent on the amino acid sequence. The activation enthalpy of dimerization
      is about 130 kJ/mol for the recombinant full-length human and bovine prion
      proteins, and between 260 and 320 kJ/mol for the other species investigated. The
      in vitro conversion assay described here permits direct molecular
      characterization of processes that might be closely related to conformational
      transitions of the prion protein in transmissible spongiform encephalopathies.

PMID- 16466742
TI  - The structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in
      complex with its coenzymes.
AB  - Formylmethanofuran:tetrahydromethanopterin formyltransferase is an essential
      enzyme in the one-carbon metabolism of methanogenic and sulfate-reducing archaea
      and of methylotrophic bacteria. The enzyme, which is devoid of a prosthetic
      group, catalyzes the reversible formyl transfer between the two substrates
      coenzyme methanofuran and coenzyme tetrahydromethanopterin (H4MPT) in a ternary
      complex catalytic mechanism. The structure of the formyltransferase without its
      coenzymes has been determined earlier. We report here the structure of the enzyme
      in complex with both coenzymes at a resolution of 2.0 A. Methanofuran,
      characterized for the first time in an enzyme structure, is embedded in an
      elongated cleft at the homodimer interface and fixed by multiple hydrophobic
      interactions. In contrast, tetrahydromethanopterin is only weakly bound in a
      shallow and wide cleft that provides two binding sites. It is assumed that the
      binding of the bulky coenzymes induces conformational changes of the polypeptide
      in the range of 3A that close the H4MPT binding cleft and position the reactive
      groups of both substrates optimally for the reaction. The key residue for
      substrate binding and catalysis is the strictly conserved Glu245. Glu245,
      embedded in a hydrophobic region and completely buried upon
      tetrahydromethanopterin binding, is presumably protonated prior to the reaction
      and is thus able to stabilize the tetrahedral oxyanion intermediate generated by
      the nucleophilic attack of the N5 atom of tetrahydromethanopterin onto the formyl
      carbon atom of formylmethanofuran.

PMID- 16466743
TI  - A flexible linkage between the dynein motor and its cargo.
AB  - We have used an antibody-Fab tag to mark the position of the cytoplasmic dynein
      amino-terminal tail domain, as it emerges from the main mass of the motor.
      Electron microscopy and single-particle image analysis reveal that the tag does
      not assume a rigidly fixed position, but instead can be found at various
      locations around the planar ring that comprises the motor's backbone. The work
      suggests that the tail is attached to the motor at a point near the ring center,
      and that the sequence immediately adjacent to this connection is flexible. Such
      flexibility argues against a simple-lever arm model for dynein force production.

PMID- 16466744
TI  - Calcium ion exchange in crystalline gelsolin.
AB  - Gelsolin is a calcium and pH-sensitive modulator of actin filament length. Here,
      we use X-ray crystallography to examine the extraction and exchange of calcium
      ions from their binding sites in different crystalline forms of the activated N
      and C-terminal halves of gelsolin, G1-G3 and G4-G6, respectively. We demonstrate
      that the combination of calcium and low pH activating conditions do not induce
      conformational changes in G4-G6 beyond those elicited by calcium alone. EGTA is
      able to remove calcium ions bound to the type I and type II metal ion-binding
      sites in G4-G6. Constrained by crystal contacts and stabilized by interdomain
      interaction surfaces, the gross structure of calcium-depleted G4-G6 remains that
      of the activated form. However, high-resolution details of changes in the ion
      binding sites may represent the initial steps toward restoration of the
      arrangement of domains found in the calcium-free inactive form of gelsolin in
      solution. Furthermore, bathing crystals with the trivalent calcium ion mimic,
      Tb3+, results in anomalous scattering data that permit unequivocal localization
      of terbium ions in each of the proposed type I and type II ion-binding sites of
      both halves of gelsolin. In contrast to predictions based on solution studies, we
      find that no calcium ion is immune to exchange.

PMID- 16466745
TI  - Stop sign violations: the role of race and ethnicity on fatal crashes.
AB  - INTRODUCTION: In contrast to age, education, and gender, which have been studied
      more frequently, the role of race/ethnicity in shaping fatal stop sign running
      incidents has received relatively little attention. It has been shown that
      failing to follow traffic laws and regulations is a major cause of motor vehicle
      crashes (MVCs) in Latin America. Does this driving behavior in Latin America
      correspond to the Hispanic community in the United States? Are Hispanics more
      likely to be at-fault concerning stop sign crossing than other racial/ethnic
      groups in the United States? METHOD: We took advantage of a 1990-1996 Fatality
      Analysis Reporting System (FARS) file with additional racial/ethnic information.
      Our file consisted of drivers who died in a MVC that occurred in an intersection
      where a stop sign was in place that involved one or more drivers with at least
      one of them failing to obey the traffic device. Descriptive statistics and
      logistic regressions were applied. RESULTS: Overall, we found no direct
      difference between African-American, White, and Hispanic drivers regarding stop
      sign running. However, we found that race/ethnicity does play an indirect role on
      this problem through its impact on drinking and driving as well as its
      interaction with age and gender. CONCLUSIONS: We found a picture that is much
      more complex than what the initial hypothesis postulated. Race/ethnicity seems to
      play a role in shaping fatal stop sign running incidents, but the mechanisms by
      which such a role is played are complex and not fully understood. IMPACT ON
      INDUSTRY: The incidence and cost of fatal stop sign running crashes may be
      reduced if prevention policies targeting the most vulnerable groups could be
      developed.

PMID- 16466746
TI  - Unusual ocular motor findings in multiple sclerosis.
AB  - In multiple sclerosis (MS), nystagmus or internuclear ophthalmoplegia (INO) are
      the usual ocular motor dysfunctions. However, in patients with focal brainstem
      lesions, other rare manifestations may be observed, such as an isolated ocular
      motor nerve palsy or complex ocular motor disturbances. We report five MS
      patients with unusual ocular motor disturbances (bilateral third nerve palsy [n =
      2], opsoclonus, Horner's syndrome and one-and-a-half syndrome). We discuss
      possible correlations between clinical disturbances and MRI abnormalities.
      Patients were seen in two MS centres. They had a confirmed diagnosis of MS and
      underwent a brain MRI and a complete neuro-ophthalmological work-up. In one case
      (opsoclonus), ocular motor manifestations were the first manifestation of MS. In
      the other four cases they occurred 3 months (Horner syndrome), 6 years and 12
      years (bilateral third nerve palsy) and 2 years (one-and-a-half syndrome) after
      the disease onset, respectively. Four out of five patients were still in a
      relapsing-remitting form of MS. In the opsoclonus case, there was no evidence of
      a brainstem lesion. A gadolinium-enhanced lesion (2 cases) or a new T2-weighted
      lesion located in the brainstem correlated with the clinical presentation. All
      patients completely or partially recovered after corticosteroid infusions. Our
      study shows some rare or previously undescribed complex ocular motor symptoms in
      MS.

PMID- 16466747
TI  - The effects of oral Cardax (disodium disuccinate astaxanthin) on multiple
      independent oxidative stress markers in a mouse peritoneal inflammation model:
      influence on 5-lipoxygenase in vitro and in vivo.
AB  - Disodium disuccinate astaxanthin ('rac'-dAST; Cardax) is a water-dispersible C40
      carotenoid derivative under development for oral and parenteral administration
      for cardioprotection of the at-risk ischemic cardiovascular patient. In
      experimental infarction models in animals (rats, rabbits, and dogs), significant
      myocardial salvage has been obtained, up to 100% at the appropriate dose in dogs.
      The documented mechanism of action in vitro includes direct scavenging of
      biologically produced superoxide anion; in vivo in rabbits, modulation of the
      complement activity of serum has also been shown. A direct correlation between
      administration of the test compound in animals and reductions of multiple,
      independent markers of oxidative stress in serum was recently obtained in a rat
      experimental infarction model. For the current study, it was hypothesized that
      oral Cardax administration would inhibit oxidative damage of multiple relevant
      biological targets in a representative, well-characterized murine peritoneal
      inflammation model. A previously developed mass spectrometry-based (LC/ESI/MS/MS)
      approach was used to interrogate multiple distinct pathways of oxidation in a
      black mouse (C57/BL6) model system. In vivo markers of oxidant stress from
      peritoneal lavage samples (supernatants) were evaluated in mice on day eight (8)
      after treatment with either Cardax or vehicle (lipophilic emulsion without drug)
      orally by gavage at 500 mg/kg once per day for seven (7) days at five (5) time
      points: (1) baseline prior to treatment (t=0); (2) 16 h following intraperitoneal
      (i.p.) injection with thioglycollate to elicit a neutrophilic infiltrate; (3) 4 h
      following i.p. injection of yeast cell wall (zymosan; t=16 h/4 h
      thioglycollate+zymosan); (4) 72 h following i.p. injection with thioglycollate to
      elicit monocyte/macrophage infiltration; and (5) 72 h/4 h thioglycollate+zymosan.
      A statistically significant sparing effect on the arachidonic acid (AA) and
      linoleic acid (LA) substrates was observed at time points two and five. When
      normalized to the concentration of the oxidative substrates, statistically
      significant reductions of 8-isoprostane-F(2alpha) (8-iso-F(2alpha)) at time point
      three (maximal neutrophil recruitment/activation), and 5-HETE, 5-oxo-EET, 11
      HETE, 9-HODE, and PGF(2alpha) at time point five (maximal monocyte/macrophage
      recruitment/activation) were observed. Subsequently, the direct interaction of
      the optically inactive stereoisomer of Cardax (meso-dAST) with human 5
      lipoxygenase (5-LOX) was evaluated in vitro with circular dichroism (CD) and
      electronic absorption (UV/Vis) spectroscopy, and subsequent molecular docking
      calculations were made using mammalian 15-LOX as a surrogate (for which XRC data
      has been reported). The results suggested that the meso-compound was capable of
      interaction with, and binding to, the solvent-exposed surface of the enzyme.
      These preliminary studies provide the foundation for more detailed evaluation of
      the therapeutic effects of this compound on the 5-LOX enzyme, important in
      chronic diseases such as atherosclerosis, asthma, and prostate cancer in humans.

PMID- 16466748
TI  - Laboratory investigation of the effects of mineral size and concentration on the
      formation of oil-mineral aggregates.
AB  - Controlled laboratory studies of the formation of oil-mineral aggregates (OMA) in
      seawater demonstrate that sediment concentration and sediment size are key
      variables for determining the quantity of oil droplets stabilised by OMA
      formation. Experiments with a single sediment size and a range of sediment
      concentrations show that as sediment concentration increases, the quantity of oil
      trapped in OMA increases abruptly. In experiments with a single sediment
      concentration and a range of sediment sizes, the quantity of oil trapped in OMA
      decreases as sediment size increases. These results provide direct support to the
      hypothesis that there is a critical sediment concentration for OMA formation.
      Below this concentration, stabilisation of oil droplets by OMA decreases rapidly,
      while above this concentration, stabilisation is extensive. The results also
      support simple geometric models of OMA formation that predict that the critical
      sediment mass concentration increases linearly with sediment particle diameter.
      These results will help to place quantitative constraint on predictions of where
      and when OMA formation will be a factor in the natural dispersal of oil
      accidentally spilled into the ocean.

PMID- 16466749
TI  - A mathematical analysis on public goods games in the continuous space.
AB  - We consider the population dynamics of two competing species sharing the same
      resource, which is modeled by the carrying capacity term of logistic equation.
      One species (farmer) increases the carrying capacity in exchange for a decreased
      survival rate, while the other species (exploiter) does not. As the carrying
      capacity is shared by both species, farmer is altruistic. The effect of
      continuous spatial structure on the performance of such strategies is studied
      using the reaction diffusion equations. Mathematical analysis on the traveling
      wave solution of the system revealed; (1) Farmers can never expel exploiters in
      any traveling wave solution. (2) The expanding velocity of the exploiter
      population invading the farmer population can be analytically determined and it
      depends only on a cost of altruism and the diffusion coefficients while it is
      independent of the benefit of altruism. (3) When the effect of altruism is small,
      the dynamics of the invasion of exploiters obeys the Fisher-KPP equation.
      Numerical calculations confirm these results.

PMID- 16466750
TI  - A stochastic model for the spread of a sexually transmitted disease which results
      in a scale-free network.
AB  - A stochastic model for the spread of a sexually transmitted disease (STD) is
      presented. To reflect varying degrees of promiscuity among individuals it is
      assumed that the infectivity of any infected individual is proportional to the
      number of previous contacts the individual has had with other infected
      individuals. In both the simple single-sex model and in the more complex two-sex
      model, the tree graphs of the infection exhibit scale-free network behaviour
      (i.e. power-law behaviour in the upper tail of the degree distribution). The
      distributions of the size of the infection and of the ring number (distance from
      the original source of the infection) are determined.

PMID- 16466751
TI  - Mathematical analysis of the global dynamics of a model for HIV infection of CD4+
      T cells.
AB  - A mathematical model that describes HIV infection of CD4(+) T cells is analyzed.
      Global dynamics of the model is rigorously established. We prove that, if the
      basic reproduction number R(0) < or = 1, the HIV infection is cleared from the T
      cell population; if R(0) > 1, the HIV infection persists. For an open set of
      parameter values, the chronic-infection equilibrium P* can be unstable and
      periodic solutions may exist. We establish parameter regions for which P* is
      globally stable.

PMID- 16466752
TI  - Endemic threshold results in an age-duration-structured population model for HIV
      infection.
AB  - In this paper we consider an age-duration-structured population model for HIV
      infection in a homosexual community. First we investigate the invasion problem to
      establish the basic reproduction ratio R(0) for the HIV/AIDS epidemic by which we
      can state the threshold criteria: The disease can invade into the completely
      susceptible population if R(0)>1, whereas it cannot if R(0)<1. Subsequently, we
      examine existence and uniqueness of endemic steady states. We will show
      sufficient conditions for a backward or a forward bifurcation to occur when the
      basic reproduction ratio crosses unity. That is, in contrast with classical
      epidemic models, for our HIV model there could exist multiple endemic steady
      states even if R(0) is less than one. Finally, we show sufficient conditions for
      the local stability of the endemic steady states.

PMID- 16466753
TI  - Periodic difference equations, population biology and the Cushing-Henson
      conjectures.
AB  - We show that for a k-periodic difference equation, if a periodic orbit of period
      r is globally asymptotically stable (GAS), then r must be a divisor of k.
      Moreover, if r divides k we construct a non-autonomous dynamical system having
      minimum period k and which has a GAS periodic orbit with minimum period r. Our
      method uses the technique of skew-product dynamical systems. Our methods are then
      applied to prove two conjectures of Cushing and Henson concerning a non
      autonomous Beverton-Holt equation which arises in the study of the response of a
      population to a periodically fluctuating environmental force such as seasonal
      fluctuations in carrying capacity or demographic parameters like birth or death
      rates. We give an equality linking the average population with the growth rates
      and carrying capacities (in the 2-periodic case) which shows that out-of-phase
      oscillations in these quantities always have a deleterious effect on the average
      population. We give an example where in-phase oscillations cause the opposite to
      occur.

PMID- 16466754
TI  - Stochastic dynamics of immunity in small populations: a general framework.
AB  - Assessment of immunological status is a powerful tool in the surveillance and
      control of infectious pathogens in livestock and human populations. The
      distribution of immunity levels in the population provides information on time
      and age dependent transmission. A stochastic model is developed for a livestock
      population which relates the dynamics of the distribution of immunity levels at
      the population level to those of pathogen transmission. A general model with K
      immunity level categories is first proposed, taking into account the increase of
      the immunity level due to an infection or a re-exposure, the decrease of the
      immunity level with time since infection or exposure, and the effect of immunity
      level on the susceptibility and the infectivity of individuals. Numerical results
      are presented in the particular cases with K=2 and K=3 immunity level categories.
      We demonstrate that for a given distribution of the immunity levels at the
      population level, the model can be used to identify quantities such as most
      likely periods of time since introduction of infection. We discuss this approach
      in relation to analysis of serological data.

PMID- 16466755
TI  - Asymptotic analysis of a chemotactic model of bacteria colonies.
AB  - An estimate of the distance between spots generated by a bacterial colony model
      is obtained. The model describes the morphogenesis of a spot pattern in colonies
      of chemotactic strains of Escherichia coli. Asymptotic methods for other cell
      chemotaxis models, which have been successfully used by previous researchers, can
      be applied also to this model. However the calculations and the result is more
      complicated for this model. The result is verified by comparing it with the
      results by numerical computations of solutions of the model.

PMID- 16466756
TI  - Backward bifurcation of an epidemic model with treatment.
AB  - An epidemic model with a limited resource for treatment is proposed to understand
      the effect of the capacity for treatment. It is assumed that treatment rate is
      proportional to the number of infectives below the capacity and is a constant
      when the number of infectives is greater than the capacity. It is found that a
      backward bifurcation occurs if the capacity is small. It is also found that there
      exist bistable endemic equilibria if the capacity is low.

PMID- 16466757
TI  - Health inequalities: The Black Report after 25 years.

PMID- 16466758
TI  - A randomized, double-blind, placebo-controlled trial of antivenom for local
      effects of green pit viper bites.
AB  - Although systemic administration of antivenom can promptly reverse coagulopathy,
      efficacy on local effects of viper venom remains to be determined. Currently,
      there has been no proven specific treatment for snakebite patients with severe
      local effects. This study is a randomized, double-blind, placebo-controlled
      trial. Patients bitten by green pit vipers (Trimeresurus albolabris or T.
      macrops) with marked limb swelling, but no severe coagulopathy requiring
      antivenom, were randomized to receive either equine F(ab')2 antivenom, or
      placebo. Twenty-eight cases were included, 14 in each group, and they had their
      limb circumferences measured on days 1, 2, 4 and 6 after interventions. The
      percentage reduction in limb circumference was significantly better in the
      antivenom group compared with the placebo group (ANOVA, P = 0.03), especially in
      the first 24 h (1.14 vs. 3.62%, in placebo and antivenom group, respectively, P =
      0.014). The reduction in pain score was similar. The plasma venom levels were not
      different at presentation but lower in the antivenom group 24h after intervention
      (P = 0.033). These data suggest that intravenous antivenom could accelerate local
      oedema resolution in humans. However, the degree is not clinically significant,
      and, therefore, general use is not recommended.

PMID- 16466759
TI  - Resting smooth muscle cells as a model for studying vascular cell activation.
AB  - Vascular smooth muscle (VSM) cells constitute the main structural components of
      tunica media. Under physiological conditions, these cells display a contractile
      phenotype and a low proliferative activity. However, they may also acquire a
      synthetic phenotype and become predominantly proliferative if stimulated under
      certain stress conditions. This capacity plays a major role in the inception and
      progression of such cardiovascular diseases as atherosclerosis, hypertension and
      restenosis. Porcine coronary smooth muscle (PCSM) cells exhibit a synthetic
      phenotype (ON cells) under standard culturing conditions, but they can be
      reverted to a contractile phenotype (OFF cells) in a serum-free medium. However,
      OFF cells can also re-acquire a synthetic phenotype (OFF/ON cells) upon serum
      administration. In the present study, proliferative and contractile behaviors
      were characterized by expression of specific differentiation markers. Taken
      together, these results demonstrate that porcine vascular smooth muscle cells can
      retain their phenotypic plasticity in culture, and thus mimic in vitro their in
      vivo differentiation states. OFF cells may thus provide a suitable model system
      in studying the mechanism(s) by which either known or unknown serum factors may
      trigger vascular smooth muscle activation. In the present study, this possibility
      was actually tested by exposing OFF cells to fetal bovine serum (FBS), PDGF-BB
      and IGF-I. Data show that only FBS could induce a synthetic phenotype in OFF
      cells, while both PDGF-BB and IGF-I failed to induce any VSM activation.

PMID- 16466760
TI  - Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: a
      pharmacodynamic drug interaction.
AB  - Calcium channel blockers and macrolide antibiotics account for many drug
      interactions. Anecdotal reports suggest interactions between the two resulting in
      severe side effects. We studied the interaction between verapamil and
      erythromycin in the rat to see whether it occurs at the pharmacokinetics or
      pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg
      verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial
      blood samples (0-6 h) were taken for determination of the drug concentrations
      using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously
      inserted lead II. Binding of the drugs to plasma proteins was studied using
      spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged
      QT but not PR interval. The combination resulted in a significant increase in PR
      interval prolongation and AV node blocks but did not further prolong QT interval.
      Pharmacokinetics and protein binding of neither drug were altered by the other.
      Our rat data confirm the anecdotal human case reports that combination of
      erythromycin and verapamil can result in potentiation of the cardiovascular
      response. The interaction appears to be at the pharmacodynamic rather than
      pharmacokinetic level hence may be extrapolated to other calcium channel
      antagonists.

PMID- 16466761
TI  - Cystine alters the renal and hepatic disposition of inorganic mercury and plasma
      thiol status.
AB  - In the present study, we determined whether cystine can inhibit, under certain
      conditions, the renal tubular uptake of inorganic mercury in vivo. We co-injected
      (i.v.) cystine with a non-toxic dose of mercuric chloride to rats and then
      studied the disposition of inorganic mercury during the next 24 h. We also
      determined if pretreatment with cystine influences the disposition of
      administered inorganic mercury. Moreover, plasma thiol status was examined after
      the intravenous administration of cystine with or without mercuric chloride.
      During the initial hour after co-injection, the renal tubular uptake of mercuric
      ions was diminished significantly relative to that in control rats. The
      inhibitory effects of cystine were evident in both the renal cortex and outer
      stripe of the outer medulla. In contrast, the renal accumulation of mercury
      increased significantly between the 1st and 12th hour after co-treatment. Urinary
      excretion and fecal excretion of mercury were greatly elevated in the rats co
      treated with cystine and mercuric chloride. Thus, when cystine and mercury are
      administered simultaneously, cystine can serve as an inhibitor of the renal
      tubular uptake of mercury during the initial hour after co-treatment. In rats
      pretreated with cystine, the renal uptake of inorganic mercury was enhanced
      significantly relative to that in rats not pretreated with cystine. This enhanced
      accumulation of inorganic mercury correlated with the increased circulating
      concentrations of the reduced cysteine and glutathione. Additionally, the present
      findings indicate that thiol status is an important determinant of renal and
      hepatic disposition, and urinary and fecal excretion, of inorganic mercury.

PMID- 16466762
TI  - Serum levels of IL-6 and its soluble receptor, TNF-alpha and chemokine RANTES in
      scorpion envenomed children: their relation to scorpion envenomation outcome.
AB  - During the present study, 30 children in Upper Egypt (less than 12 years old)
      were admitted to Pediatric Intensive Care Unit because of scorpion envenomation.
      They were compared with 20 apparently normal children of matching age and sex as
      controls. The victims and controls were subjected to complete clinical
      examination and full blood picture. The serum levels of interleukin-6 (IL-6),
      soluble IL-6 receptor (sIL-6R), regulated upon activation normal T cells
      expressed and secreted (RANTES ) and tumour necrosis factor-alpha (TNF-alpha)
      were determined once for the controls and twice for the victims, the first sample
      on admission and the second sample after 24h. All victims showed significantly
      higher mean values of IL-6, sIL-6R, RANTES, TNF-alpha, and leucocytic count both
      on admission and on the follow up when compared with controls. According to the
      clinical manifestations of envenomation, 40% of the victims had a mild
      envenomation manifestation, while 60% of them had severe manifestations. The
      severely envenomed children showed significantly higher mean values of IL-6, sIL
      6R, TNF-alpha, RANTES and leucocytic count both on admission and on the follow up
      samples when compared with the mild cases. The non-survival victims (five
      victims) showed significantly higher mean values of IL-6, sIL-6R, TNF-alpha,
      RANTES and leucocytic count both on admission and on the follow up samples in
      comparison to the survivals. Furthermore, those fatal cases showed a non
      significant decline in the serum levels of IL-6, sIL-6R, TNF-alpha, RANTES and
      leucocytic count on the following up samples, while the survivals showed a
      significant decline in the serum levels of these parameters on the following up
      samples. In conclusion, these data revealed that IL-6, sIL-6R, TNF-alpha and
      chemokine, RANTES are involved in the pathogenesis of scorpion envenomation and
      correlated with its severity.

PMID- 16466763
TI  - Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of
      its activation by either PACT or double-stranded RNA.
AB  - A major component of the cellular antiviral system is the latent protein kinase
      PKR, which is activated by binding to either double-stranded RNA (dsRNA) or the
      cellular PACT protein. Activated PKR phosphorylates the translation initiation
      factor eIF2, thereby inhibiting viral and cellular protein synthesis and virus
      replication. To evade the antiviral effects of PKR, many viruses, including
      influenza A virus, have evolved multiple mechanisms. For influenza A virus, the
      non-structural (NS1A) protein plays a major role in blocking activation of PKR
      during virus infection. The mechanism by which the NS1A protein inhibits PKR
      activation in infected cells has not been established. In the present study, we
      first carried out a series of in vitro experiments to determine whether the NS1A
      protein could utilize a common mechanism to inhibit PKR activation by both PACT
      and dsRNA, despite their different modes of activation. We demonstrated that the
      direct binding of the NS1A protein to the N-terminal 230 amino acid region of PKR
      can serve as such a common mechanism and that this binding does not require the
      RNA-binding activity of the NS1A protein. The lack of requirement for NS1A RNA
      binding activity for the inhibition of PKR activation in vivo was established by
      two approaches. First, we showed that an NS1A protein lacking RNA-binding
      activity, like the wild-type (wt) protein, blocked PKR activation by PACT in
      vivo, as well as the downstream effects of PKR activation in cells, namely, eIF2
      phosphorylation and apoptosis. In addition, we demonstrated that PKR activation
      is inhibited in cells infected with a recombinant influenza A virus expressing
      NS1A mutant protein that cannot bind RNA, as is the case in cells infected with
      wild-type influenza A virus.

PMID- 16466764
TI  - Interaction between endoplasmic reticulum stress and caspase 8 activation in
      retrovirus MoMuLV-ts1-infected astrocytes.
AB  - The murine retrovirus, MoMuLV-ts1, induces progressive paralysis and immune
      deficiency in FVB/N mice. We have reported previously that ts1 infection causes
      apoptosis in astrocytes via endoplasmic reticulum (ER) and mitochondrial stress
      (Liu, N., Kuang, X., Kim, H.T., Stoica, G., Qiang, W., Scofield, V.L., Wong,
      P.K.Y. Wong. 2004. Possible involvement of both endoplasmic reticulum- and
      mitochondria-dependent pathways in MoMuLV-ts1-induced apoptosis in astrocytes. J.
      NeuroVirol. 10, 189-198). In the present study, we show that caspase 8 activation
      in these cells is mediated through ER stress-associated elevation of death
      receptor DR5 and the C/EBP homologous protein (GADD153/CHOP), an ER stress
      initiated transcription factor, rather than through TNFalpha and TNF-R1
      interactions on the cell surface. Treatment with Z-IETD-FMK, a specific inhibitor
      of caspase 8 enzymatic activity, reduced ER stress by two mechanisms: by
      inhibiting caspase 8 activation, and by preventing cleavage of the ER-associated
      membrane protein BAP31 into BAP20, which exacerbates the ER stress response.
      These findings suggest that caspase 8- and ER stress-associated apoptotic
      pathways are linked in ts1-infected astrocytes.

PMID- 16466765
TI  - Modified tobacco mosaic virus particles as scaffolds for display of protein
      antigens for vaccine applications.
AB  - Display of peptides or proteins in an ordered, repetitive array, such as on the
      surface of a virus-like particle, is known to induce an enhanced immune response
      relative to vaccination with the "free" protein antigen. The coat protein of
      Tobacco mosaic virus (TMV) can accommodate short peptide insertions into the
      primary sequence, but the display of larger protein moieties as genetic fusions
      to the capsid protein has not been possible. We employed a randomized library
      approach to introduce a reactive lysine at the externally located amino terminus
      of the coat protein, which facilitated biotinylation of the capsid. To
      characterize display of heterologous proteins on the virion surface, we bound a
      model antigen (green fluorescent protein (GFP)-streptavidin (SA), expressed and
      purified from plants) to the biotinylated TMV particles, creating a GFP-SA
      decorated virus particle. A GFP-SA tetramer loading of 26% was obtained,
      corresponding to approximately 2200 GFP moieties displayed per intact virion. We
      evaluated the immunogenicity of GFP decorated virions in both mice and guinea
      pigs and found augmented humoral IgG titers in both species, relative to unbound
      GFP-SA tetramer. Next, we fused an N-terminal fragment of the Canine oral
      papillomavirus L2 protein to streptavidin. With TMV display, the L2 protein
      fragment was significantly more immunogenic than uncoupled antigen when tested in
      mice. By demonstrating the presentation of whole proteins, this study expands the
      utility of TMV as a vaccine scaffold beyond that which is possible by genetic
      manipulation.

PMID- 16466767
TI  - Prediction of the temperature dependency of Henry's law constant using poly
      parameter linear free energy relationships.
AB  - The ability to predict the temperature dependence of air/water partitioning is
      important for the environmental fate modeling of organic pollutants. Here,
      literature data for the temperature dependence of air/water partitioning of some
      200 compounds have been used to derive poly-parameter linear free energy
      relationships (pp-LFER) for predicting air/water partition coefficients at
      temperatures between 0 and 45 degrees C. The compounds used for calibrating the
      pp-LFERs span a range of almost 10 orders of magnitude in the partition constants
      and they cover a large variety of functional groups. Very good fits (r(2)>0.99)
      were obtained at all temperatures. Hence, these pp-LFERs should serve as a
      valuable tool for integrating the temperature dependence of air/water
      partitioning into fate modeling of organic compounds. In the environment one will
      quite often encounter a situation where water and air do not have the same
      temperatures. This situation is shortly discussed in the appendix.

PMID- 16466766
TI  - Modeling the competitive effect of phosphate, sulfate, silicate, and tungstate
      anions on the adsorption of molybdate onto goethite.
AB  - The mobility of Mo in soils and sediments depends on several factors including
      soil mineralogy and the presence of other oxyanions that compete with Mo for the
      adsorbent's retention sites. Batch experiments addressing Mo adsorption onto
      goethite were conducted with phosphate, sulfate, silicate, and tungstate as
      competing anions in order to produce competitive two anions adsorption envelopes,
      as well as competitive two anions adsorption isotherms. Tungstate and phosphate
      appear to be the strongest competitors of Mo for the adsorption sites of
      goethite, whereas little competitive effects were observed in the case of
      silicate and sulfate. Mo adsorption isotherm from a phosphate solution was
      similar to the one from a tungstate solution. The charge distribution multi-site
      complexation (CD-MUSIC) model was used to predict competitive adsorption between
      MoO(4)(2-) and other anions (i.e., phosphate, sulfate, silicate and tungstate)
      using model parameters obtained from the fitting of single ion adsorption
      envelopes. CD-MUSIC results strongly agree with the experimental adsorption
      envelopes of molybdate over the pH range from 3.5 to 10. Furthermore, CD-MUSIC
      prediction of the molybdate adsorption isotherm show a satisfactory fit of the
      experimental results. Modeling results suggest that the diprotonated monodentate
      complexes, FeOW(OH)(5)(-0.5) and FeOMo(OH)(5)(-0.5), were respectively the
      dominant complexes of adsorbed W and Mo on goethite 110 faces at low pH. The
      model suggests that Mo and W are retained mainly by the formation of monodentate
      complexes on the goethite surface. Our results indicate that surface complexation
      modeling may have applications in predicting competitive adsorption in more
      complex systems containing multiple competing ions.

PMID- 16466768
TI  - Intra-individual variations and time trends 1991-2001 in human serum levels of
      PCB, DDE and hexachlorobenzene.
AB  - BACKGROUND: An important question is whether human serum levels of persistent
      organic pollutants has continued to decrease during the last decades. The aim of
      this study was to assess intra-individual variations over time of serum levels of
      2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), 1,1-dichloro-2,2-bis(4-chlorophenyl)
      ethene (p,p'-DDE) and hexachlorobenzene (HCB), considering the impact of a number
      of possible determinants. METHODS: Blood samples were drawn for the same 39
      subjects in 1991 and 2001. Interviews were made at both occasions. Lipid adjusted
      serum concentrations of CB-153, p,p'-DDE and HCB were determined in both sets of
      blood samples using gas chromatography-mass spectrometry. The fatty acid
      composition of the serum lipids was analyzed by means of gas-liquid
      chromatography. RESULT: The CB-153 concentrations in serum had averagely
      decreased with 34% in between 1991 and 2001 (p<0.001). Of individual determinants
      only increasing BMI was associated with decreasing CB-153 levels (beta=-1.0, 95%
      CI -1.8, -0.2, p=0.01), explaining 13% of the variation. The average decrease of
      p,p'-DDE was 55%, and could only weakly be associated with a relative increase of
      BMI (beta=-1.0, 95% CI -2.3, 0.2, p=0.09), explaining only 5% of the variation.
      The average decrease of HCB was 53%, and was associated only with high fish
      consumption in 1991, explaining 12% of the variation. CONCLUSIONS: The results
      support a continuing decrease in human body burdens of PCBs, DDE and HCB during
      the 1990s. The explanatory factors relative change of BMI and fish consumption
      explained only a minor part of the time-related variations in serum levels.

PMID- 16466769
TI  - Oxidative and energetic efficiency of different electrochemical oxidation
      processes for chloroanilines abatement in aqueous medium.
AB  - The oxidative efficiency and energy consumption, in the degradation of
      chloroanilines by anodic oxidation, indirect oxidation with electrogenerated
      hydrogen peroxide and electro-Fenton have been compared, using a laboratory
      system driven by a LabVIEW virtual controller. Solutions were oxidized in an
      undivided cell, where H(2)O(2) was generated electrochemically by reduction of
      atmospheric oxygen bubbled at a carbon cloth cathode. The electro-Fenton process
      showed the best degradation power, in terms of efficiency of removal and energy
      consumption. This process was applied to the purification of a solution obtained
      by washing a polluted soil. Under laboratory conditions, electro-Fenton removed
      75% COD of this wastewater with a specific energy consumption of 0.3kWh per gram
      of COD, corresponding to 41.8kWhm(-3).

PMID- 16466770
TI  - Water quality and fish size affect toxicity of endosulfan, an organochlorine
      pesticide, to rainbow trout.
AB  - The acute toxicity of endosulfan in juvenile rainbow trout (Oncorhynchus mykiss,
      10.61+/-1.69 g) was evaluated in glass aquaria under static conditions. Nominal
      concentrations of endosulfan in the toxicity test ranged from 1.3 microg l(-1) to
      29 microg l(-1). The concentrations of endosulfan that killed 50% of the rainbow
      trout within 24-h (24-h LC50), 48-h LC50, 72-h LC50, and 96-h LC50 were 19.78,
      8.89, 5.28, and 1.75 microg l(-1), respectively. None of the unexposed control
      fish died, and the first fish died 4 h after exposure to 26.3 microg l(-1) of
      endosulfan. Survival of fish was significantly increased with increasing fish
      size and decreased with decreased fish size at the same temperature (p<0.001).
      Temperature also had a significant effect on survival of fish. Alkalinity at
      levels above 20 mg l(-1) as CaCO3 significantly increased survival of fish at
      19.78 microg l(-1) of endosulfan. Increasing alkalinity from 20 mg l(-1) as CaCO3
      to 42 or higher concentrations tested in this study (121 mg l(-1) as CaCO3)
      significantly increased survival of fish (p<0.01). Total hardness ranging from 55
      mg l(-1) as CaCO3 to 126 mg l(-1) as CaCO3 did not affect survival of fish
      exposed to endosulfan. Endosulfan toxicity was found to be irreversible when fish
      were exposed to minimum concentrations of endosulfan tested. Histologically, fish
      gills had lamellar edema, separation of epithelium from lamellae, lamellar
      fusion, and swelling of the epithelial cells. Melanomacrophage centers were
      scattered throughout the trunk kidney, head kidney, and spleen. The liver of
      endosulfan-exposed fish had severe focal necrosis. None of these lesions were
      seen in unexposed control fish. Results indicate that alkalinity, temperature,
      and fish size affect endosulfan toxicity of rainbow trout.

PMID- 16466771
TI  - Organochlorine pesticides in soil profiles from Tianjin, China.
AB  - Soil cores were collected from soils at five sites in Tianjin area for the
      determination of hexachlorocyclohexane isomers (HCHs, including alpha-HCH, beta
      HCH, gamma-HCH and delta-HCH), dichlorodiphenyltrichloroethane and metabolites
      (DDXs, including p,p'-DDT, p,p'-DDE and p,p'-DDD) and total organic carbon (TOC).
      The levels and vertical distributions of HCHs and DDXs are studied. Results show
      that the application of pesticides in the past years was the major contributor of
      HCHs and DDXs accumulation in the sampling areas. Significant positive
      correlations were seen between the residual and application amounts of HCHs and
      DDXs. Wastewater irrigation did not bring a significant contribution of HCHs or
      DDXs into the soils. HCHs and DDXs concentrations peak at the surface and decline
      in soil profile with depth, while fluctuations were observed in the plow layers
      of some cultivated soils caused by frequent cultivation activities and batch
      irrigation. Positive correlations were observed between the contents of TOC and
      HCHs and DDTs. Although the amounts of HCHs application in all sampling sites are
      larger than DDXs, at surface and near surface layers of most sampling sites, the
      concentrations of summation operatorHCHs are lower than summation operatorDDXs.
      The composition of DDXs in the applied pesticides and sampled soils indicates
      that there is no recent DDT input at the sample areas.

PMID- 16466772
TI  - Characterization of atmospheric dry deposition particulates in Kobe, Japan.
AB  - The sources and character of individual metal and metalloid particles from
      atmospheric dry depositions in Kobe, Japan were investigated. Japan faces long
      range pollutant transportation from northeastern Asia during winter and spring.
      Information regarding their properties and sources is useful for evaluating their
      affects on the environment and human health. Individual metal and metalloid
      particles that were collected for every 24 h on the plate, which was designed to
      reduce a local turbulence, were characterized for their composition, diameter,
      and deposition fluxes using a field emission scanning electron microscope with an
      energy dispersive X-ray spectrometer. Approximately 3,000 metal and metalloid
      particles were classified into 14 types based on their composition and further
      classified into four groups based on their distribution patterns. They are (A) Fe
      O, Fe-Ba-Sb-Cu-S-Ti-O, Fe-Zn-O, Zn-O, Ni-O, and Mn-Fe-O; (B) Cu-Zn-O and Cu-Sn-O;
      (C) Pb-O, Sn-Sb-O, and Ag-O; (D) Pb-Zn-Cl-Si-S-O and Bi-Cl-O. From these data,
      this study suggests their sources as the Asian continent (Group A), local source
      (Group B), multiple sources (Group C), and incineration process (Group D). This
      study shows (1) the sources and character of individual metal and metalloid
      particles from short-term atmospheric depositions in Kobe, Japan and (2)
      application of individual particle analysis for atmospheric depositions.

PMID- 16466773
TI  - Determination of gas phase adsorption isotherms--a simple constant volume method.
AB  - Single and ternary solute gas phase adsorption isotherms were conducted in this
      study to evaluate the effectiveness of a simple constant volume method, which was
      utilized by using Tedlar gas sampling bags as a constant volume batch reactor.
      For this purpose, gas phase adsorption of toluene, methyl ethyl ketone (MEK), and
      methyl isobutyl ketone (MIBK) on two types of activated carbons, BPL-bituminous
      base and OVC--coconut base, were investigated. For the single solute adsorption,
      the experimental adsorption data were found to be well correlated with Freundlich
      and Myers adsorption equations. The pore size distribution of adsorbents was
      found to affect their adsorption capacities; its effect was dependant on the
      solute concentration. The ternary adsorption experimental isotherms were
      accurately predicted by using the well-known model, i.e., ideal adsorbed solution
      theory (IAST).

PMID- 16466775
TI  - Acute toxicity of leachates of tire wear material to Daphnia magna--variability
      and toxic components.
AB  - Large amounts of tire rubber are deposited along the roads due to tread wear.
      Several compounds may leach from the rubber and cause toxicity to aquatic
      organisms. To investigate the toxic effects of tire wear material from different
      tires, rubber was abraded from the treads of twenty-five tires. Leachates were
      prepared by allowing the rubber to equilibrate with dilution water at 44 degrees
      C for 72 h. Then the rubber was filtered from the leachates, and test organisms
      (Daphnia magna) were added. Forty-eight hour EC50s ranged from 0.5 to >10.0 g l(
      1). The toxicity identification evaluation (TIE) indicated that non-polar organic
      compounds caused most of the toxicity. UV exposure of the filtered tire leachates
      caused no significant increase in toxicity. However, when tested as unfiltered
      leachates (the rubber was not filtered from the leachates before addition of D.
      magna) photo-enhanced toxicity was considerable for some tires, which means that
      test procedures are important when testing tire leachates for aquatic (photo)
      toxicity. The acute toxicity of tire wear for Daphnia magna was found to be <40
      times a predicted environmental concentration based on reports on the
      concentration of a tire component found in environmental samples, which
      emphasizes the need for a more extensive risk assessment of tire wear for the
      environment.

PMID- 16466774
TI  - Leaching behavior of Cr(III) in stabilized/solidified soil.
AB  - The leaching behavior of chromium was studied using batch leaching tests, surface
      complexation modeling and X-ray absorption near edge structure (XANES)
      spectroscopy. A contaminated soil sample containing 1330 mg-Cr kg(-1) and 25600
      mg-Fe kg(-1) of dry soil was stabilized/solidified (S/S) with 10% cement, 25%
      cement, 10% lime and a mixture of 20% flyash and 5% lime. The XANES analysis
      showed that Cr(III) was the only Cr species in untreated soil and S/S-treated
      samples. The leachate Cr concentration determined using the toxicity
      characteristic leaching procedure (TCLP) was reduced from 5.18 mg l(-1) for
      untreated soil to 0.84 mg l(-1) for the sample treated with 25% cement. The Cr
      leachability in untreated and treated soil samples decreased dramatically as the
      pH increased from 3 to 5, remained at similar levels in the pH range between 5
      and 10.5, and further decreased at pH>10.5. Modeling results indicated that the
      release of Cr(III) was controlled by adsorption on iron oxides at pH<10.5, and by
      precipitation of Ca(2)Cr(2)O(5).6H(2)O at pH>10.5.

PMID- 16466776
TI  - Endocrine and metabolic alterations in the mink (Mustela vison) due to chronic
      phytoestrogen exposure.
AB  - Phytoestrogens are natural components of plant-based food items with beneficial
      health effects. The aim of the present study was to investigate the chronic
      effects of dietary phytoestrogens, genistein (8 mg kg(-1) day(-1)) and beta
      sitosterol (50 mg kg(-1) day(-1)), on the weight regulation of the mink (Mustela
      vison). The parental generation was exposed from August 2002 to May-June 2003 to
      either beta-sitosterol or genistein, while the kits were exposed through
      gestation and lactation. Food consumption and body masses were monitored monthly.
      Plasma lipid, glucose, total protein and hormone (ghrelin, leptin,
      triiodothyronine and thyroxine) concentrations were measured from the parents in
      August 2002, January 2003 and at the end of the experiment in May-June 2003 when
      the kits were 21 days of age. Relative food intake was higher in the beta
      sitosterol-exposed minks than in the control or genistein minks in September
      2002. Plasma leptin and total protein concentrations were lower in the beta
      sitosterol kits compared to the control kits. Furthermore, plasma ghrelin levels
      and liver phosphorylase activities of the mink kits were higher due to genistein
      exposure. In mink kits, exposure to both phytoestrogens reduced the plasma
      thyroxine concentrations. The kidney glycogen concentrations and the muscle
      phosphorylase activities of phytoestrogen-treated adult minks were elevated. The
      results of this study suggest that minks are sensitive to perinatal phytoestrogen
      exposure.

PMID- 16466777
TI  - Formation of estrogenic products from environmental phthalate esters under light
      exposure.
AB  - Phthalate esters (PEs) have been suspected to be environmental endocrine
      disruptors and the detailed mechanism remains unclear. The activities of these
      chemicals can be enhanced through chemical modification under the environmental
      conditions. We demonstrate that PEs acquire unequivocal estrogenic activity by
      light exposure. Through UV exposure of an aqueous PE solution, one active
      photoproduct, identified as 4-hydroxyPE (PE-4OH) based on its characteristic UV
      and mass spectra, was detected in an estrogen receptor alpha-dependent
      transactivation assay. PE-4OH was effectively generated by UV 290 nm. The PE-4OH
      production accompanied H2O2 generation in a UV dose-dependent manner. Both PE and
      UV irradiation were indispensable in the generation of H2O2. Addition of H2O2 to
      the PE solution increased PE-4OH production under UV irradiation. The PE-4OH
      production was also observed in the PE reaction with the Fenton reagent
      generating hydroxyl radical without UV irradiation. The proposed mechanism for PE
      4OH production based on these results is such that by PE-mediated
      photosensitization H2O2 is generated from O2 and H+ and decomposed to hydroxyl
      radical, thus oxidizing the PE benzene ring. The PEs-4OH are remarkably active
      estrogenic products of PEs and would be involved in ER-mediated endocrine
      disruption.

PMID- 16466778
TI  - Effect of metal ions and humic acid on the dechlorination of tetrachloroethylene
      by zerovalent iron.
AB  - The dechlorination of tetrachloroethylene (PCE) by zerovalent iron (Fe(0)) in the
      presence of metal ions and humic acid was investigated. In the absence of metal
      ion and humic acid, 64% of the initial PCE was dechlorinated after 125 h with the
      production of ethane and ethene as the major end products. The dechlorination
      followed pseudo-first-order kinetics and the normalized surface rate constant
      (k(SA)) for PCE dechlorination was (3.43+/-0.61)x10(-3)lm(-2)h(-1). Addition of
      metal ions enhanced the dechlorination efficiency and rate of PCE, and the
      enhancement effect followed the order Ni(II)>Cu(II)>Co(II). The k(SA) for PCE
      dechlorination in the presence of metal ions were 2-84 times higher than that in
      the absence of metal ions. X-ray photoelectron spectroscopy (XPS) showed that
      Cu(II) and Ni(II) were reduced by Fe(0) to zerovalent metals, and resulted in the
      formation of bimetallic system to accelerate the dechlorination reaction. On the
      contrary, humic acid out-competed the reactive sites on iron surface with PCE,
      and subsequently decreased the dechlorination efficiency and rate of PCE by
      Fe(0). However, the reactivity of Fe(0) for PCE dechlorination in the presence of
      metal ions and humic acid increased by a factor of 3-161 when compared to the
      iron system containing humic acid alone. Since humic acid and metal ions are the
      most often found co-existing compounds in the contaminated aquifers with
      chlorinated hydrocarbons, results obtained in this study is useful to better
      understand the feasibility of using Fe(0) for long-term application to the
      remediation of contaminated sites.

PMID- 16466779
TI  - The role of pH in the fermentative H2 production from an acidogenic granule-based
      reactor.
AB  - The role of pH in the fermentative H(2) production from an upflow acidogenic
      granule-based reactor was investigated in this study. Experimental results show
      that all H(2) partial pressure, H(2) production rate and H(2) yield were pH
      dependent, in the range of 2.8 x 10(4)-5.2 x 10(4)Pa, 61-145 ml-H(2)l(-1)h(-1)
      and 0.68-1.61 mol-H(2)mol-glucose(-1), respectively. The maximum H(2) partial
      pressure was observed at pH 3.4, while both maximum H(2) production rate and H(2)
      yield were found at pH 4.2. Acetate, propionate, butyrate, i-butyrate, valerate,
      caporate and ethanol were present in the effluent of this UASB reactor, and their
      distribution was also pH-dependent. As pH was decreased from 4.2 to a lower level
      of 3.4 or increased to a higher level of 6.3, the fermentative type of this H(2)
      producing reactor would shift from butyrate-type to caporate- or ethanol-type.
      Thermodynamic analysis was performed to explore the possible metabolic pathways
      of caproate and valerate formation. The metabolic pathway of caproate formation
      was pH-dependent, while that of valerate formation was pH-independent. A neural
      network model was designed, trained and validated. It was able to successfully
      describe the daily variations of H(2) partial pressure and H(2) yield of the
      reactor, and to predict its steady state performance at various pHs.

PMID- 16466780
TI  - Thrombin-activatable fibrinolysis inhibitor and activated factor XII in patients
      with systemic lupus erythematosus.

PMID- 16466781
TI  - The fractionated Toona sinensis leaf extract induces apoptosis of human ovarian
      cancer cells and inhibits tumor growth in a murine xenograft model.
AB  - OBJECTIVE: Aqueous extract from the leaves of Toona sinensis Roem. has been shown
      to have an anti-proliferative effect on human lung cancer cells. In this study,
      we analyzed the anti-cancer activity/effect of different extraction fractions of
      the extract from T. sinensis leaves on ovarian cancer cells. METHODS: Cell
      viability was determined by XTT cell proliferation assay and cell survival assay.
      Apoptotic effect was detected by morphological analysis and immunoblotting. Cell
      cycle effect was evaluated by flow cytometry analysis and immunoblotting. In vivo
      therapeutic effect was evaluated by the subcutaneous inoculation of SKOV3 cells
      in nude mice (Foxnlnu/Foxnlnu) model. RESULTS: TSL2 of T. sinensis was more
      cytotoxic than other fractions and exhibited selectivity for ovarian cancer cell
      lines. TSL2 arrested SKOV3 ovarian cancer cells at the G2/M phase and induced
      cancer cells go through apoptotic pathway. Ex vivo xenograft study of nude mice
      showed that intraperitoneal injection of TSL2 was able to suppress the
      proliferation of ovarian cancer cells without significant nephrotoxicity, liver
      toxicity, or bone marrow suppression.

PMID- 16466782
TI  - Genetics, genomics, and molecular biology of sex determination in small animals.
AB  - The genomic revolution is beginning to facilitate advances in canine and feline
      medicine, as illustrated in our research. Our studies are focused upon
      identifying the gene mutation that causes canine Sry-negative XX sex reversal, a
      disorder of sex determination in which chromosomal females (78,XX) develop
      testicular tissue, becoming either XX true hermaphrodites with ovotestes, or XX
      males with bilateral testes. A genome-wide screen, using mapped markers in our
      pedigree of Sry-negative XX sex reversed dogs founded upon the American cocker
      spaniel, identified five chromosomal regions in which the causative gene may be
      located. The canine genome was used to identify the canine homologue of goat
      Pisrt1 and so determine that canine and caprine Sry-negative XX sex reversal are
      genetically heterogeneous. A second goal of our research is to determine the
      molecular mechanism by which the mutation causes testis induction. Thus far, we
      have reported gonadal Sry and Sox9 expression patterns in normal embryos, which
      have temporal and spatial patterns similar to those reported in humans, sheep,
      and pigs. Once gene mutations causing such inherited disorders are identified,
      DNA tests will become a part of general veterinary practice, advancing both
      diagnostic techniques and preventative medicine.

PMID- 16466783
TI  - LightUp probes in clinical diagnostics.
AB  - The LightUp Probe technology has now matured and reached the phase where it has
      been implemented in commercial reagent kits, i.e. the ReSSQ product line. Several
      properties of the LightUp probes make them particularly suitable for clinical
      settings. For instance, extraordinary shelf life and a chemical stability that
      allows convenient fridge storage. The origin of the higher stability of LightUp
      probe kits compared to others, based on alternative probe technologies, is partly
      the relatively good stability of cyanine dyes but also the resistance towards
      nucleases and proteases of the synthetic DNA analogue peptide nucleic acid that
      is used as the sequence recognizing element in LightUp probes. It is clear from
      recent trends in the PCR amplification hardware technology that the
      instrumentation is becoming more flexible and less adapted for dedicated probe
      chemistries. This will pave the way for increased standardization in the field of
      DNA diagnostics and the development of cross-platform assays. In the present
      review the LightUp technology will briefly be presented and discussed. The
      utility of the technology will be illustrated by examples from cytomegalovirus
      quantification and monitoring of the viral load of the SARS Coronavirus. An
      example of cancer diagnostics by detection of altered gene expression patterns
      will also be shown.

PMID- 16466784
TI  - Stress corrosion cracking of NiTi in artificial saliva.
AB  - OBJECTIVES: This paper aimed to study the mechanism of the cracking of
      orthodontic NiTi wire. METHODS: Two orthodontic NiTi wires were subjected: (1)
      optical and scanning electron microscopy (SEM) to observe the fracture surface;
      (2) energy dispersive X-ray spectroscopy to determine the composition of the
      surface product; (3) anodic polarization to remove the surface product. Samples
      of NiTi alloy were subjected to the constant loading test to study the stress
      corrosion cracking (SCC) behavior of NiTi shape memory alloy in artificial
      saliva. RESULTS: The results showed that there were three typical areas at the
      fracture surface of NiTi orthodontic wire. Area '1' was a tool-made notch. Crack
      initiated from the root of this notch and propagated to form Area '2', which was
      perpendicular to the wire axis and covered by surface film. This film consisted
      of Na, K, Cl, P, S and O except Ni and Ti. The cracking process of NiTi alloy
      under the constant loading test depended on the pH of saliva and applied stress.
      The crack length was about 262microm, the longest at 300MPa and pH 3.0.
      SIGNIFICANCE: A tool-made notch in orthodontic NiTi wires can cause SCC. At high
      stress and low pH, this NiTi alloy was most sensitive to cracking.

PMID- 16466785
TI  - Examining the intergenerational transmission of violence in a New Zealand birth
      cohort.
AB  - OBJECTIVE: This paper examines whether exposure to interparental violence in
      childhood predicts subsequent involvement in interpartner violence and violent
      crime after controlling for potentially confounding factors. METHOD: The
      investigation analyses data from the Christchurch Health and Development Study, a
      prospective, longitudinal study of a birth cohort of over 1000 New Zealand young
      adults studied at multiple assessment points from birth to the age of 25.
      RESULTS: After controlling for potentially confounding risk factors, observed
      associations between exposure to interparental violence in childhood and
      increased risks of both (a) psychological interpartner violence perpetration and
      victimization and (b) violent crime, were reduced to statistical non
      significance. No statistically significant associations were observed between
      exposure to interparental violence in childhood and increased risk of physical
      interpartner violence perpetration or victimization. CONCLUSIONS: It is concluded
      that the effects of childhood exposure to interparental violence on subsequent
      interpartner violence are weak and largely explained by the psychosocial context
      within which childhood exposure to interparental violence occurs.

PMID- 16466786
TI  - Attachment and social support in the prediction of psychopathology among young
      adults with and without a history of physical maltreatment.
AB  - OBJECTIVE: The purpose of this study was to examine the roles that social support
      and attachment play with regard to psychopathology among young adults with and
      without a history of physical maltreatment. Attachment was conceptualized in
      terms of the dimensions of view of self and view of other. Attachment and social
      support were examined individually and concurrently as protective factors.
      METHOD: The sample consisted of 956 young adults, 294 of whom had a history of
      physical abuse. Individuals filled out a series of questionnaires inquiring about
      current attachment, social support, and psychopathology symptoms. A regression
      design was used, examining how well attachment and/or social support predicted
      current psychopathology. RESULTS: Results indicated that attachment security,
      particularly when characterized by a positive view of self, strongly predicted
      lower levels of psychopathology, irrespective of abuse status. Notably, view of
      self was a substantially larger predictor than was view of other or social
      support for individuals with and without a history of physical maltreatment.
      Among maltreatment subtypes, psychological abuse emerged as the largest predictor
      of psychopathology. CONCLUSIONS: The current study suggests that the attachment
      dimension of view of self is fundamental in predicting current psychopathology
      level, irrespective of abuse history. In addition, the subtype of psychological
      abuse deserves further investigation as a risk factor.

PMID- 16466787
TI  - Psychological defense styles, childhood adversities and psychopathology in
      adulthood.
AB  - OBJECTIVE: The present study explores the link between reported sexual and/or
      physical abuse and psychological defense styles, as well as the association of
      both with psychological distress in adulthood. In two patient samples that differ
      in psychological distress and somatization, we examine whether the adversities
      reported and immature defense styles are associated with psychopathological
      symptoms. METHOD: We examined 266 consecutive inpatients in the psychosomatic
      department and 109 consecutive inpatients who had been treated for low-back pain
      in the orthopedic department of a German university hospital. Psychological
      defense styles were assessed by a two-factor solution of the German modified
      adaptation of the Defense Mechanism Inventory (DMI), childhood adversities by a
      structured interview, psychological distress by the SCL-90-R, and somatization by
      the Screening for Somatoform Disorders (SOMS). RESULTS: Both samples demonstrated
      a significant link between immature defense styles and the extent of overall
      psychological distress as well as somatization. Reported sexual and/or physical
      abuse of patients in both patient samples was directly associated with
      somatization. CONCLUSION: Recollections of sexual and/or physical abuse in
      childhood and immature defense styles have an association with psychopathology in
      adulthood. This finding suggests that immature defense styles may act, in part,
      as mediators between the adversities investigated and adult psychopathology.

PMID- 16466788
TI  - Risk factors and protective factors in relation to subjective health among adult
      female victims of child sexual abuse.
AB  - OBJECTIVE: To investigate the relationships between risk and protective factors
      and health outcome in a sample of adult females who had been victims of child
      sexual abuse. METHOD: Both person- and variable-oriented analyses were applied to
      questionnaire data from a non-clinical group of women (n = 152) reporting sexual
      abuse during childhood. RESULTS: Six groups with different patterns of risk and
      protective factors were found by cluster analysis. Two groups (Good Coping and
      Support Compensation) had significantly better health than expected in spite of
      severe abuse. Self-esteem and social support were strong predictors of health in
      the regression models. CONCLUSION: The relationships between risk and protective
      factors and health may be different in different groups of victims of child
      sexual abuse. Self-esteem was closely related to health outcome displaying the
      importance of this concept in clinical practice. Availability of resources seems
      to be more important for health outcomes than the amount of risk factors.

PMID- 16466789
TI  - Trauma symptoms among infants exposed to intimate partner violence.
AB  - OBJECTIVE: To determine whether infants have a traumatic response to intimate
      partner violence (male violence toward their female partner; IPV) experienced by
      their mothers, two questions were explored: (1) Is the number of infant trauma
      symptoms related to the infant's temperament and the mother's mental health? (2)
      Does severity of violence moderate those relationships? METHODOLOGY: Forty-eight
      mothers reported whether their 1-year-old infants experienced trauma symptoms as
      a result of witnessing episodes of IPV during their first year of life. Mothers
      also reported on their own trauma symptoms that resulted from experiences of IPV.
      RESULTS: For those infants experiencing severe IPV and whose mothers exhibit
      trauma symptoms, we were able to predict whether infants exhibited trauma
      symptoms (b = .53, p < .01). This was not true for children who witnessed less
      severe IPV (b= -.14, ns). Maternal depressive symptoms and difficult infant
      temperament did not predict infant trauma symptoms for either group of infants.
      CONCLUSION: Mothers report that infants as young as 1-year-old can experience
      trauma symptoms as a result of hearing or witnessing IPV. The significant
      relationship between infant and maternal trauma symptoms, especially among those
      infants experiencing severe IPV, are consistent with the theory of relational
      PTSD. Findings suggest that interventions for mothers and families need to
      consider the influence of the severity of IPV on very young children.

PMID- 16466790
TI  - Jagged-1hi or Delta-1hi thymic stromal cell populations can trigger acquisition
      of Thy-1 and loss of B220.
AB  - Effects of endogenous Notch ligands Jagged-1 and Delta-1 on maturation markers in
      adult mouse lymphocytes were checked in vitro on putative thymocyte precursors
      from bone marrow and on DN3 cells from the thymus. Both populations were
      cocultured with stromal cells (Small M, Histochem Cell Biol 2005;123:513)
      naturally expressing high levels of either Jagged-1 or Delta-1. Initially the
      bone marrow cells were Thy-1.2(neg) while the majority were B220(hi). These
      trends were reversed by culture on both the Jagged-1(hi) and Delta-1(hi)
      monolayers. Then DN3 thymocytes were cultured with stroma expressing these two
      ligands and the T cell receptor beta chain was expressed more clearly after
      coculture on Delta-1(hi) stroma. These findings indicate that stromal cells with
      endogenous Jagged-1 as well as Delta-1 could initiate early changes toward T cell
      commitment while Delta-1 favored later alphabeta-TCR development.

PMID- 16466791
TI  - Naphthalene treatment alters liver intermediary metabolism and levels of steroid
      hormones in plasma of rainbow trout (Oncorhynchus mykiss).
AB  - To assess the effects of naphthalene on liver intermediary metabolism and plasma
      steroid hormones, immature female rainbow trout (Oncorhynchus mykiss), in a first
      experiment, were intraperitoneally injected (2 microLg(-1)) with vegetable oil
      alone (control) or containing naphthalene (10 and 50 mgkg(-1)) and returned to
      their tanks. At 1, 3, and 6h after injection, eight fish were sampled from each
      group. A second experiment was similarly designed but used fish intraperitoneally
      implanted (10 microLg(-1)) with slow-release coconut oil implants alone (control)
      or containing naphthalene at doses of 10 and 50 mgkg(-1) body weight that were
      sampled 1, 3, and 5 days after injection. At each sampling time, plasma hormone
      levels (cortisol and 17beta-estradiol) and metabolic parameters in plasma
      (glucose and lactate) and liver (glucose, lactate, and glycogen levels and HK,
      GK, GPase, GDH, FBPase, and PK activities) were assessed. Changes described for
      both hormonal systems resulted in a decrease in plasma levels of cortisol and
      17beta-estradiol. Changes observed in intermediary metabolism described effects
      in several pathways of liver energy metabolism due to naphthalene. These changes
      can be summarized as increased glycogenolysis, use of exogenous glucose, and
      glycolysis and decreased gluconeogenesis. The increased energy production in
      liver suggested by these changes can be related to the increased detoxification
      activity known to occur in liver after PAH exposure, and can be also related
      directly or indirectly to the changes observed in the levels of plasma steroids.

PMID- 16466793
TI  - Anatomical functional and cognitive determinants of semantic memory disorders.
AB  - Contemporary debates on the 'semantic memory' construct revolve around three main
      topics: (1) the functional and anatomical relationships between episodic and
      semantic memory; (2) the format of semantic representations and their
      relationships with the underlying sensory-motor processes; (3) the categorical
      organization of semantic memory. The aim of the present review is to demonstrate
      that there is a common thread linking these different aspects of semantic memory.
      This thread is represented by the interdependence of mechanisms involved in the
      construction of semantic memory and the content of semantic representations. In
      particular, I suggest there is a continuity between: (a) the mechanisms of
      acquisition of episodic and semantic memory; (b) semantic representations and
      sensory-motor processes preliminary to the acquisition of these representations.
      This continuity has important implications for the format of semantic
      representations and the brain structures subserving the organisation of various
      categories of knowledge.

PMID- 16466792
TI  - Interaction of potash and decis in the ecophysiology of a freshwater fish
      Oreochromis mossambicus.
AB  - Interaction of potash and decis in the ecophysiology of a freshwater fish,
      Oreochromis mossambicus, was studied. It was found that 300, 550 and 700 mgL(-1)
      of potash were sublethal (LC(0)), median lethal (LC(50)), and toxic (LC(100)) to
      O. mossambicus for 96h exposure, respectively. For decis, 96 h LC(100,) LC(50),
      and LC(0) was 0.4, 0.25, and 0.1 mgL(-1), respectively. Sublethal concentrations
      of potash and decis were exposed to fishes individually and in combination for 28
      days. The results revealed that the combined effect of these chemicals was more
      highly toxic to food intake, growth, and conversion efficiencies than the
      individual chemicals. The marker enzymes (acid phosphatase, alkaline phosphatase,
      aspartate transaminase, alanine transaminase) were also analyzed in blood, liver
      and muscle. The enzyme activities were decreased in liver and muscle. On the
      other hand, serum exhibited increased activities of marker enzymes. The results
      were tested statistically and interpreted accordingly.

PMID- 16466794
TI  - ADHD and schizophrenia phenomenology: visual scanpaths to emotional faces as a
      potential psychophysiological marker?
AB  - Commonalities in the clinical phenomenology and psychopharmacology of ADHD and
      schizophrenia are reviewed. The potential of psychostimulants to produce
      psychotic symptoms emphasizes the need for objective psychophysiological
      distinctions between these disorders. Impaired emotion perception in both
      disorders is discussed. It is proposed that visual scanpaths to facial
      expressions of emotion might prove a potentially useful psychophysiological
      distinction between ADHD and schizophrenia. There is consistent evidence that
      both facial affect recognition and scanpaths to facial expressions are impaired
      in schizophrenia, with emerging empirical evidence showing that facial affect
      recognition is impaired in ADHD also. Brain imaging studies show reduced activity
      in the medial prefrontal and limbic (amygdala) brain regions required to process
      emotional faces in schizophrenia, but suggest more localized loss of activity in
      these regions in ADHD. As amygdala activity in particular has been linked to
      effective visual scanning of face stimuli, it is postulated that condition
      specific breakdowns in these brain regions that subserve emotional behavior might
      manifest as distinct scanpath aberrations to facial expressions of emotion in
      schizophrenia and ADHD.

PMID- 16466795
TI  - Waxworks and the performance of anatomy in mid-18th-century Italy.
AB  - Anatomical waxworks lay at the centre of a composite world of social interaction
      in mid-18th-century Bologna. Sponsored by Pope Benedict XIV and included among
      Grand Tour attractions, they earned fame and authority for wax-modellers such as
      Anna Morandi, Giovanni Manzolini and Ercole Lelli. By dissecting bodies, making
      waxwork models of them and demonstrating their anatomical collections, these
      artificers became protagonists of the world of anatomy. Offering representations
      of the inner body some thought more faithful than the real thing, their
      collections gave expression to a new set of relations between the role of
      artefacts in the production and communication of knowledge, the emergence of new
      apparatuses for viewing and investigating the human body, the legacy of codified
      visual conventions and the authenticating power of natural spectacle.

PMID- 16466796
TI  - Interleukin IL-12 blocks a specific subset of the transcriptional profile
      responsive to UVB in epidermal keratinocytes.
AB  - Interleukin-12 (IL-12) is a proinflammatory and immunomodulatory cytokine that
      plays a critical role it in innate and adaptive immunity by inducing production
      of interferon-gamma and other cytokines. IL-12 was shown to block the ultraviolet
      light-induced immunosuppression, important in cancer immunosurveillance,
      cutaneous allergies and inflammation. To characterize the molecular effects of IL
      12 in epidermis we used large DNA microarrays and defined the transcriptional
      changes in human epidermal keratinocytes 1 h, 4 h, 24 h, and 48 h after treatment
      with IL-12, as well as in cells treated with both IL-12 and UV light. In
      keratinocytes, IL-12 activates STAT3 and STAT4; surprisingly, despite activating
      these transcription factors, the transcriptional effects of IL-12 did not rise
      above background levels. However, pre-treatment of keratinocytes with IL-12
      strongly modulated the transcriptional effects of UV. Pre-treatment with IL-12
      enhanced the UV-mediated regulation of 20 and antagonized the regulation of 263
      genes. IL-12 enhanced the induction of cytokines by UV. IL-12 antagonized the
      suppression of cytoskeletal, junctional, metabolic, mitochondrial, and
      extracellular matrix proteins, while antagonizing the induction of certain
      signaling proteins and RNA processing enzymes. We conclude that in the epidermis,
      IL-12 interferes with a specific subset of transcriptional effects of UV
      irradiation.

PMID- 16466798
TI  - Detecting neuronal activity changes using an interspike interval algorithm
      compared with using visual inspection.
AB  - A universally accepted method for efficiently detecting neuronal activity changes
      (NACs) in neurophysiological studies has not been established. Visual inspection
      is still considered to be one of the most reliable methods, although it is
      limited when it is used for analyzing large quantities of data. In this study, an
      algorithm that considers interspike intervals (ISIs) was developed to define the
      onset of NACs. Two criteria, involving the mean and the standard deviation (S.D.)
      of the ISIs during a control period, were used in the ISI algorithm to evaluate
      the NACs that occurred during a detection period. The first, an ISI decrease of
      more than 1 S.D. from the mean ISI of the control period, proved to be an
      effective criterion for qualifying the increased NACs (firing rate increases).
      The second, an ISI increase greater than 3 S.D.s, efficiently demarcated periods
      of decreased NACs (firing rate decreases). Statistically significant correlations
      between the detection of NAC onset times by the ISI algorithm and the detection
      of those times by visual inspections were observed after offline analyses of
      recorded neuronal activity. The present results suggest that this ISI algorithm
      is a reliable and efficient way of defining the onset of NACs.

PMID- 16466797
TI  - Effect of the matrix structure and concentration of polymer-immobilized Ni2+
      iminodiacetic acid complexes on retention of IgG1.
AB  - Terpolymer bead particles (100-350 microm in diameter) were prepared by
      suspension radical polymerization from methacrylate esters [2,3-epoxypropyl
      methacrylate (GMA), 2-(2-hydroxyethoxy)ethyl methacrylate (DEGMA) and ethylene
      dimethacrylate (EDMA)] and subsequently derivatized affording iminodiacetic acid
      (IDA) chelating sorbents. The sorbents differed in pore volumes (0-0.7 cm3/g) and
      specific surface areas (0.03-9.8 m2/g) of their matrices as well as in the
      amounts of immobilized Ni2+-IDA complexes (0.03-1.58 mmol/g). The binding of
      imidazole was studied by frontal chromatography to evaluate the accessibility of
      Ni2+-IDA complexes. It was found that an increase in the bonded imidazole content
      with increasing immobilized Ni2+-IDA concentration was strongly dependent on the
      matrix morphology. A higher pore volume of the matrix significantly improved the
      utilizability of Ni2+-IDA complexes for imidazole binding. The performance of the
      sorbents based on two porous matrices with immobilized Ni2+-IDA concentration
      (0.1-1.58 mmol/g) differing in pore size distributions was compared in
      immobilized metal affinity chromatography (IMAC) of monoclonal mouse
      immunoglobulin IgG1 specific against human choriogonadotropic hormone (GTH-spec
      IgG1). The results have shown that sorbents based on matrix with large pores (up
      to 20 microm in diameter) exhibited high protein binding capacities. The GTH-spec
      IgG1 (Mw=158,000) was eluted from all the sorbents in its native form as was
      confirmed by MALDI-TOF.

PMID- 16466799
TI  - SuperState: a computer program for the control of operant behavioral
      experimentation.
AB  - Operant behavioral researches require precise control of experimental devices for
      delivering stimuli and monitoring behavioral responses. The author developed a
      software solution named SuperState for controlling hardware devices and running
      reinforcement schedules. The Microsoft Windows compatible software was written by
      use of an object-oriented programming language Borland Delphi 5.0, which has
      simplified the programming of the application. SuperState is a stand-alone easy
      to-use green software, without the need for the experimenter to master any
      scripting languages. It features: (1) control of multiple operant cages running
      independent reinforcement schedules; (2) enough cage devices (16 digital inputs
      and 16 digital outputs for each cage) suitable for the need of most operant
      behavioral equipments; (3) control of most standard ISA-type digital interface
      cards including Med-Associates Super-port cards and a PCI-type card AC6412, and
      highly expandable to support other PCI-type interface cards; (4) high-resolution
      device control (1ms); (5) a built-in real-time cumulative recorder; (6) extensive
      data analyzing including event recorder, cumulative recorder, block analyzing;
      the summarized results can be transferred easily to Microsoft Excel spreadsheets
      through the Clipboard.

PMID- 16466800
TI  - Optimizing conditions and avoiding pitfalls for prolonged axonal tracing with
      carbocyanine dyes in fixed rat spinal cords.
AB  - We have characterized a method of labeling of axons in the post-mortem spinal
      cord using a silastic disc holding pins coated with DiI and DiO at the rostral
      and caudal ends of the cord. We optimized the DiI and DiO tracing techniques
      under different conditions of fixative concentration (1% versus 4%
      paraformaldehyde, PF), at room temperature (RT) versus 37 degrees C for up to 24
      weeks. Crystal coated pins embedded in a silastic disc provided a novel method of
      dye application. Confocal microscopy of longitudinal sections showed DiI and DiO
      labeled both the axonal membrane and myelin sheath. DiI diffused significantly
      longer distances than DiO. Both dyes migrated greater distances at 37 degrees C
      compared with RT. No significant difference of dye labeling was found between 1%
      and 4% PF fixation. After prolonged incubation there was evidence that dye
      diffused through the aqueous medium and produced circumferential labeling of the
      cord. Placing a wax seal around the labeling site prevented this non-contiguous
      labeling. Labeling of myelin sheaths at extended distances into the cord
      suggested that dye could migrate between cells with prolonged incubation periods.
      Our data suggested that higher temperature facilitated dye diffusion along the
      axons, and demonstrated that with caution DiI and DiO could be used as specific
      tracers in the same spinal cords.

PMID- 16466801
TI  - The ulnar test: a method for the quantitative functional assessment of
      posttraumatic ulnar nerve recovery in the rat.
AB  - The assessment of recovery of the neuromuscular function following nerve lesion
      and repair is one of the main goals of peripheral nerve researchers. The forelimb
      model has recently seen an increase in its employment for experimental nerve
      repair studies especially because of the availability of the grasping test for
      assessing the functional recovery of one of its major nerves, the median nerve.
      Nerve repair studies sometimes require the use of more than one nerve to simulate
      severe clinical situations and, in this case, the ulnar nerve is often used
      together with the median nerve. However, a test for assessing ulnar nerve
      functional recovery is yet not available. To fill this gap, we have developed and
      experimentally tested a method for the functional assessment of posttraumatic
      ulnar nerve recovery in the rat. Animal testing using this method is simple,
      quick and provides the animal with minimal distress. The method proved to be
      effective in detecting the date on which recovery starts after ulnar nerve
      impairment and in following its improvement, over time. The availability of this
      new test is expected to further increase the employment of forelimb experimental
      nerve models instead of the more disabling hindlimb models.

PMID- 16466802
TI  - MRI compatible electrodes for the induction of amygdala kindling in rats.
AB  - The rat electrical kindling model has been widely utilized in epilepsy research.
      This study aimed to identify the optimum "MRI compatible" bipolar stimulating and
      recording electrodes to enable serial MRI acquisition in this model. Two types of
      custom-made electrodes (gold and carbon) were compared with commercial platinum
      iridium alloy electrodes for suitability based on size, effect on image quality
      and kindling induction. The custom-made gold electrodes, based on these
      parameters, were found to be most suitable. These electrodes enable the study of
      epileptogenesis utilizing MRI in this model of temporal lobe epilepsy (TLE).

PMID- 16466803
TI  - Measurement of CGRP in dried blood spots using a modified sandwich enzyme
      immunoassay.
AB  - Calcitonin gene-related peptide (CGRP) has roles as a neurotransmitter,
      neuromodulator and trophic factor. CGRP has been reported to be elevated in
      neonatal blood of children with autism or mental retardation as compared with
      normal subjects by recycling immuno-affinity chromatography (RIC). While CGRP
      detection in neonatal blood is thus important, it is not easy to detect CGRP in
      dried blood spots because of the limitations of sample volume and the specificity
      and the sensitivity of available assay systems. In the present study, we modified
      a "Sandwich Enzyme Immunoassay" for the purpose of detecting CGRP in blood spot
      eluate. We have prepared blood spots from blood collected from normal human
      subjects and measured CGRP level in eluates from these blood spots. Instead of a
      purification step, we have introduced a pre-incubation step and used washed
      erythrocytes as a dilution solution. The modified assay has good recovery and
      specificity and appropriate dilution curves. We have compared the eluate levels
      with levels in serum and plasma from the same individuals and find that CGRP
      levels in blood spot eluate were similar to those of serum and plasma. Thus, the
      newly modified EIA may be a useful method for the detection of CGRP in blood spot
      eluate.

PMID- 16466804
TI  - Measuring cell viability with membrane impermeable zinc fluorescent indicator.
AB  - Recent findings suggest that the accumulation of cytoplasmic zinc [Zn2+]i is a
      ubiquitous component in the cell death cascade. Zn2+ can be liberated from
      intracellular stores following oxidative stress and contribute to cell death
      processes. Here we show that the membrane/cell impermeable Zn2+ fluorescent
      indicator Newport Green (NG), which is non-toxic and impermeable to the membranes
      of healthy cells, can label unhealthy cells in tissue slices in a manner
      comparable to the traditional viability indicator propidium iodide (PI). Using
      confocal microscopy, we detected PI labeled nuclei colocalized with NG
      fluorescence. Our results indicate that cells which absorbed PI into their nuclei
      also allowed cell-impermeable Zn2+ dye to penetrate their plasma membranes,
      subsequently exhibiting cytosolic and nuclear fluorescence. As in PI staining, we
      observed marked increases in NG fluorescence in damaged/dead cells of tissue
      slices. Two other cell impermeable fluorescent Zn2+ dyes, Fluozin-3 and Zinpyr-4,
      also stained cytosolic Zn2+ in PI labeled cells. Our data indicates that the
      application of a Zn2+ fluorescent indicator is a fast, simple, non-toxic and
      reliable method for visualizing cell viability within in vitro tissue
      preparations. Accordingly, we demonstrate that intracellular accumulation of Zn2+
      correlates with neuronal death.

PMID- 16466805
TI  - Inhibition by human sera of botulinum neurotoxin-A binding to synaptosomes: a new
      assay for blocking and non-blocking antibodies.
AB  - The mouse protection assay (MPA), which is an in vivo assay, is currently the
      most widely used method for monitoring blocking antibodies (Abs) in botulinum
      neurotoxin (BoNT)-treated patients. In recent studies we found that a number of
      the regions on the heavy (H) subunit of BoNT/A that bind blocking mouse Abs
      coincided, or overlapped, with the regions that bind to mouse synaptosomes
      (snps). This suggested that blocking anti-BoNT/A Abs would be expected to inhibit
      BoNT/A binding to snps. In the present work, we analyzed sera from 58 cervical
      dystonia (CD) patients who had been treated with BOTOX (a preparation of BoNT/A
      serotype) for blocking Abs by MPA and by their abilities to inhibit in vitro the
      binding of 125I-labeled active BoNT/A or inactive toxin (toxoid) to mouse brain
      snps. With active 125I-labeled BoNT/A-snps binding, the MPA-positive sera (n =
      30) displayed inhibition levels that were distinctly higher (mean = 21.1 +/- 5.8)
      than those obtained with MPA-negative sera (n = 28) (mean = -1.3 +/- 3.9; p <
      0.0001) or control sera (n = 19) (mean = -3.4 +/- 2.8; p < 0.0001). Similarly,
      inhibition levels by MPA-positive sera of 125I-labeled toxoid snp-binding (mean =
      48.6 +/- 8.7) were distinctly higher than inhibition by MPA-negative sera
      (mean=10.0+/-7.6; p < 0.0001) or control sera (mean = 1.8 +/- 6.9; p < 0.0001).
      Thus, using labeled active toxin or toxoid, the inhibition assay correlated very
      well with the MPA. The inhibitory activity of the non-protective sera generally
      correlated with the duration of survival after toxin challenge (correlation
      coefficients of inhibition: active toxin = 0.445; p = 0.0167; inactive toxoid =
      0.774; p < 0.0001). It is concluded that the snp-inhibition assay reported here
      is reliable, reproducible and correlates very well with the MPA. It requires much
      less serum (0.75% of the amount needed for the MPA) and is considerably less
      costly than the MPA. With either 125I-labeled active toxin or toxoid, it is
      possible to distinguish CD sera that have blocking Abs from those that lack such
      Abs. Since the results with the toxoid were as discriminating as those of the
      active toxin, it would not even be necessary to use active toxin in these assays.

PMID- 16466806
TI  - Recursive artifact windowed-single tone extraction method (RAW-STEM) as periodic
      noise filter for electrophysiological signals with interfering transients.
AB  - The single tone extraction method (STEM) is a well developed algorithm for
      estimating the frequency, amplitude, and phase of one periodic signal or a single
      tone in complex temporal signals. This method is useful in neuroscience research
      since it provides an efficient simple means to remove line frequency noise
      present in many types of signal measurements. However, the method encounters
      problems when the signal contains transients such as a stimulus artifact which
      distort the estimation of power line parameters. Here we report a modification of
      STEM that overcomes this limitation. In this new method we call recursive
      artifact windowed (RAW)-STEM, the line frequency noise is removed for each single
      epoch by estimating the three parameters (frequency, amplitude and phase) of each
      line frequency after windowing the time period containing an interfering
      transient and iteratively applying the STEM. In a simulation study we evaluated
      its performance for electrophysiological data with a stimulus artifact and
      demonstrated advantages of the RAW-STEM over the classic STEM. The RAW-STEM is
      able to efficiently extract the 60 Hz parameter, requiring less than five
      iterations, with a precision of 0.007-2% depending on the parameters. It does not
      suffer from the problem of ringing following the stimulus artifact or distortion
      of electrophysiological signals. It is fast enough to be used for single trial
      analyses in electrophysiological studies. The RAW-STEM may be widely useful for
      the removal of periodic noise since it can be applied even when there are
      multiple interfering transients in the recording.

PMID- 16466807
TI  - Evaluation of Na+/K+ pump function following repetitive activity in mouse
      peripheral nerve.
AB  - After conduction of prolonged trains of impulses the increased Na+/K+ pump
      activity leads to hyperpolarization. The aim of this study was to develop a mouse
      model to investigate the Na+/K+ pump function in peripheral nerve by measuring
      the decrease in excitability during activity-dependent hyperpolarization. Acute
      electrophysiological investigations were carried out in seven adult mice. Nerve
      excitability was evaluated by tracking the change in threshold current after 5
      min of 100 Hz stimulation of the tibial nerve at ankle. We developed a threshold
      tracking system that allowed us to follow several excitability measures
      simultaneously from the evoked plantar compound muscle action potential (CMAP)
      and sciatic compound nerve action potential (CNAP). Three minutes after
      repetitive supramaximal stimulation maximal CMAP and CNAP amplitudes recovered
      but the threshold was increased approximately 40% for motor axons approximately
      34% for axons generating CNAP. The threshold recovered with a rate of 3.8%/minute
      that was similar for nerve and motor responses. By tracking the effect of
      polarizing currents we found evidence of activity dependent hyperpolarization,
      and our data suggest that the observed threshold change after repetitive
      stimulation of the mouse tibial nerve is an indicator of the Na+/K+ pump function
      in vivo. Evaluation of activity-dependent hyperpolarization may be an important
      indicator of axonal ability to cope with Na+ load.

PMID- 16466808
TI  - Quantitative no-net-flux microdialysis permits detection of increases and
      decreases in dopamine uptake in mouse nucleus accumbens.
AB  - A number of investigators are using the quantitative no-net-flux microdialysis
      technique to monitor basal neurotransmitter dynamics in discrete brain regions of
      behaving animals. The predictive validity of the probe extraction fraction (Ed)
      for quantifying decreases in the rate of dopamine (DA) clearance from the
      extracellular space is well documented. It was recently suggested, however, that
      Ed may be insensitive to increases in DA clearance. Here we report that the Ed
      for DA in the nucleus accumbens (NAc) of the behaving mouse is increased
      following pharmacological inactivation of kappa-opioid receptors, a treatment
      previously shown to augment DA uptake. The Ed obtained in control mice and those
      that received the long-acting kappa-opioid receptor antagonist, nor
      binaltorphimine (nor-BNI), satisfied the requirement that the mean values of each
      were lower than the mean value in vitro for the same probes immersed in well
      stirred artificial cerebrospinal fluid. The Ed was increased in the NAc of nor
      BNI-treated mice as compared to saline-treated control animals. The corresponding
      increase in the DA uptake rate was quantified by using the Ed values to calculate
      a change in the apparent clearance rate constant. Nor-BNI treatment did not alter
      the apparent extracellular dopamine concentration represented by the point of no
      net-flux indicating that the rates of DA uptake and release were both increased.

PMID- 16466809
TI  - Visualization of integral and peripheral cell surface proteins in live
      Caenorhabditis elegans.
AB  - To study the abundance of specific receptors and other cell surface proteins at
      synapses, it would be advantageous to specifically label these proteins only when
      inserted in the plasma membrane. We describe a method that allows to
      fluorescently label cell surface proteins in live and behaving animals, namely in
      the nematode Caenorhabditis elegans. Proteins such as subunits of the levamisole
      sensitive nicotinic acetylcholine receptor (nAChR) were epitope-tagged at their
      extracellular C-termini, and fluorescent antibodies against those tags were
      injected into the body fluid. These antibodies specifically labelled synaptic
      regions on the cell surface of muscles and neurons, and simultaneous use of
      different tags facilitated co-localization studies. Quantification of the
      fluorescence is possible, as verified by demonstrating that mutations in ric-3
      and unc-38, which cause behavioural resistance to cholinergic agonists, strongly
      reduce or even abolish nAChR cell surface expression. We also used this method to
      visualize the extracellular peripheral membrane protein ODR-2, which is related
      to a neurotoxin-like protein regulating vertebrate neuronal nAChRs. Likewise,
      fluorescent alpha-bungarotoxin, when injected, bound to certain nAChRs in the
      pharynx and the nervous system. This showed that, theoretically, any molecular
      interaction of sufficient affinity may be used to specifically label cell surface
      structures in live nematodes.

PMID- 16466810
TI  - Vaccine-induced protection against Leishmania amazonensis is obtained in the
      absence of IL-12/23p40.
AB  - Protozoa of the genus Leishmania are intracellular parasites of macrophages and
      may cause diverse clinical forms of leishmaniasis, including cutaneous, diffuse
      cutaneous, mucocutaneous and visceral leishmaniasis. Infection with L. major in
      mice indicates that a protective immune response is achieved when Th1 cells are
      developed. Thus, adoptive or vaccine-induced protection against leishmaniasis is
      largely dependent on cell-mediated immunity and IFN-gamma production. Induction
      of a Th1 response is dependent on the presence of IL-12 whilst lymphocytes are
      activated. This study was aimed at evaluating the role of IL-12 during infection
      with L. amazonensis and after vaccination with Leishvacin (killed Leishmania
      amazonensis promastigotes), since the role of this cytokine in vaccine-induced
      immunity with this preparation in experimental models or in humans is not yet
      elucidated. Hence, C57BL/6 interleukin-12-deficient mice (IL-12p40(-/-)) and wild
      type controls (wt) were infected with L. amazonensis and the course of infection,
      parasite burden and cytokine production were compared. IL-12p40(-/-) mice were
      more susceptible to L. amazonensis than wt: lesions and parasite burden were
      larger in IL-12p40(-/-) when compared to wt. Interestingly, IL-4 was not produced
      in the absence of IL-12 in response to infection with L. amazonensis. To evaluate
      the role of IL-12 in the vaccine-induced immunity against L. amazonensis
      infection, IL-12p40(-/-) wt mice were vaccinated in the base of the tail and
      subsequently challenged with L. amazonensis in the footpads. Surprisingly,
      vaccinated IL-12p40(-/-) mice developed smaller lesions and had fewer parasites
      in footpads than non-vaccinated controls. Lymph node and spleen cells from
      vaccinated IL-12p40(-/-) mice did not produce high levels of IFN-gamma in
      response do in vitro stimulus with antigen. Hence, partial protection against
      infection with L. amazonensis could be obtained in the absence of functional IL
      12 and a typical Th1 response.

PMID- 16466811
TI  - Effects of sevoflurane and TIVA with propofol on middle ear pressure.
AB  - OBJECTIVE: To evaluate the effects of sevoflurane and TIVA with propofol on
      middle ear pressure and to show the importance of anesthesia without using any
      inhalational agents during middle ear surgery. STUDY DESIGN: A prospective,
      randomized controlled clinical study. METHODS: In this study, 25 male children
      that were scheduled for circumcision were randomised into two groups. Group I
      (n=13) received TIVA with propofol and group II (n=12) received sevoflurane.
      Baseline tympanometry reading was performed on each ear just before anesthesia.
      The next tympanometry reading was taken 10min after applying the laryngeal mask.
      Data were analysed by Mann-Whitney U (between groups) and Wilcoxon tests (within
      groups). RESULTS: Mean MEP values in 26 ears of 13 boys in group I did not show
      any significant difference before and after the anesthesia with propofol
      (p>0.05). In group II mean MEP values in 24 ears of 12 boys showed a significant
      increase after the anesthesia with sevoflurane (p<0.001). No significant
      difference was found between the MEP values of the two groups before the
      anesthesia (p>0.05), and MEP values measured during the anesthesia were
      significantly higher in group II (p=0.007). CONCLUSION: Sevoflurane may increase
      the middle ear pressure and TIVA with propofol may be used in middle ear
      operations more safely than sevoflurane.

PMID- 16466812
TI  - Management of pediatric airway granular cell tumor: role of laryngotracheal
      reconstruction.
AB  - OBJECTIVE: To discuss the role of laryngotracheal reconstruction (LTR) in
      granular cell tumor (GCT) and to highlight the importance and seriousness of GCT
      in pediatric airway cases. METHODS: A historical literature review was performed
      and a GCT case from the University of Miami Pediatric Otolaryngology Clinic is
      presented to highlight the role of LTR in the treatment of GCT. RESULTS: A case
      of a GCT of the laryngotracheal airway is reported and the management is
      discussed. Histological discussion and a review of the literature are included
      regarding GCT. This case is the third reported in the English literature of two
      synchronous GCT lesions of the upper airway repaired with a laryngotracheal
      reconstruction. CONCLUSIONS: In the authors' experience once conservative
      management consisting of endoscopic debulking has failed the treatment of choice
      for GCTs of the pediatric airway that are unresectable is a single stage
      laryngotracheal reconstruction with negative frozen section pathology to assure
      total wide local excision.

PMID- 16466813
TI  - Downregulation of vitellogenin gene activity increases the gustatory
      responsiveness of honey bee workers (Apis mellifera).
AB  - In the honey bee (Apis mellifera), young workers usually perform tasks in the
      nest while older workers forage in the field. The behavioral shift from nest-task
      to foraging activity is accompanied by physiological and sensory changes so that
      foragers can be characterized by a higher juvenile hormone (JH) level, a lower
      vitellogenin protein titer, and an increased responsiveness to water and sucrose
      stimuli. JH was hypothesized to be the key mediator of behavioral development,
      physiology, and sensory sensitivity in honey bee workers. Recent research,
      however, has shown that JH is controlled by the hemolymph vitellogenin level,
      which implies that the fat body specific vitellogenin gene can be a key regulator
      of behavioral change. Here, we show that downregulation of vitellogenin activity
      by RNA interference (RNAi) causes an increase in the gustatory responsiveness of
      worker bees. Our observations suggest that vitellogenin is an important regulator
      of long-term changes in honey bee behavior.

PMID- 16466814
TI  - Volumetric structural brain abnormalities in men with schizophrenia or antisocial
      personality disorder.
AB  - Brain abnormalities are found in association with antisocial personality disorder
      and schizophrenia, the two mental disorders most implicated in violent behaviour.
      Structural magnetic resonance imaging was used to investigate the whole brain,
      cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen,
      thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor,
      occipito-parietal regions in 13 men with antisocial personality disorder, 13 men
      with schizophrenia and a history of violence, 15 men with schizophrenia without
      violent history and 15 healthy non-violent men. Compared to controls, the
      antisocial personality disorder group displayed reductions in whole brain volume
      and temporal lobe as well as increases in putamen volume. Both schizophrenia
      groups regardless of violence history exhibited increased lateral ventricle
      volume, while the schizophrenia group with violent history showed further
      abnormalities including reduced whole brain and hippocampal volumes and increased
      putamen size. The findings suggest that individuals with antisocial personality
      disorder as well as those with schizophrenia and a history of violence have
      common neural abnormalities, but also show neuro-anatomical differences. The
      processes by which they came to apparently common ground may, however, differ.
      The finding of temporal lobe reductions prevalent among those with antisocial
      personality disorder and hippocampal reduction in the violent men with
      schizophrenia contributes support for the importance of this region in mediating
      violent behaviour.

PMID- 16466815
TI  - Resveratrol affects CYP1A expression in rainbow trout hepatocytes.
AB  - Resveratrol (RVT), a polyphenolic phytoalexin found in a variety of food
      products, including grapes and peanuts, is a well-characterized aryl hydrocarbon
      receptor (AhR) antagonist in mammalian cell lines. The lack of a reliable tool to
      block AhR signaling in rainbow trout (Oncorhynchus mykiss) prompted this study to
      evaluate the utility of RVT as an AhR antagonist in a piscine system. Trout
      hepatocytes in primary culture were exposed to varying doses of RVT (10(-5)-10(
      12) M) either in the presence or absence of a well-established AhR agonist, beta
      naphthoflavone (BNF). Indeed, BNF significantly elevated CYP1A and AhR protein
      expression in trout hepatocytes, and this response was inhibited at high (10(-5)
      10(-7) M), but not low (10(-8)-10(-10) M), RVT doses. However, RVT alone at low
      doses (10(-8)-10(-10) M) significantly elevated CYP1A protein expression compared
      to control hepatocytes. This higher protein response with RVT was completely
      abolished with actinomycin D and cycloheximide suggesting transcriptional and
      translational regulation of CYP1A induction. Also, RVT at low (10(-9) M), but not
      high (10(-5) M), dose significantly elevated CYP1A1 mRNA transcript levels in BNF
      primed hepatocytes supporting transcriptional modulation. Taken together, RVT is
      an effective AhR antagonist, but induces CYP1A expression at lower doses (<10(-8)
      M) in trout hepatocytes.

PMID- 16466816
TI  - Orthostatic hypotension in the healthy elderly.
AB  - Orthostatic hypotension (OH) is a common problem in elderly people causing
      several complications such as falls and fractures. In recent years, it was
      noticed that OH seems to have an association with cardiovascular risk factors
      including cerebrovascular events, higher nocturnal blood pressure levels, and
      arterial stiffness. In this study, we aimed to evaluate the prevalence of OH in
      our healthy elderly people and its association with blood pressures, left
      ventricular mass, plasma insulin, age, and autonomic tests including heart rate
      response (HRR) to valsalva maneuver, heart rate variation (HRV) during deep
      breathing, HRR to standing. A total of 61 subjects (35 male/26 female) were
      enrolled and completed the study. Nine out of 61 (14.7%) were found to have OH.
      When demographic features and study parameters were compared in both groups
      (subjects with OH: 9 and non-OH: 52), no difference in blood glucose, sodium,
      potassium, calcium, body mass index, systolic and diastolic blood pressures, HRR
      to valsalva maneuver, HRV during deep breathing, HRR to standing were found
      between the groups. While fasting plasma insulin level was significantly higher
      in non-OH group than those in OH group (p<0.05), left ventricular mass index was
      significantly higher in subjects with OH (p<0.05). In conclusion, OH is a
      prevalent condition in healthy elderly people and its relation with
      cardiovascular risk factors like increased left ventricular mass index and
      impaired blood pressure control need more studies to demonstrate such an
      association and responsible mechanisms.

PMID- 16466817
TI  - Application of proteomics in cardiovascular medicine.
AB  - Proteomics is an emerging field that has the potential to uncover new therapeutic
      targets for the treatment and prevention of cardiovascular disease, as well as
      new diagnostic biomarkers for early disease detection. The basic strategy when
      carrying out proteomic analysis of cardiovascular disease is to compare the
      protein complements of diseased hearts or sera with controls. Any proteins that
      have altered expression between the two groups can be studied further for their
      involvement in disease pathogenesis. A number of steps need to be taken to
      identify changes in protein expression, including sample preparation, protein
      separation, imaging, and protein identification. Such studies are already
      underway in some cardiovascular conditions including dilated cardiomyopathy and
      atrial fibrillation. This review provides a summary of the techniques used in
      proteomic analysis and their application to cardiovascular research.

PMID- 16466818
TI  - A welfare economics foundation for health inequality measurement.
AB  - The empirical literature on the measurement of health inequalities is vast and
      rapidly expanding. To date, however, no foundation in welfare economics exists
      for the proposed measures of health inequality. This paper provides such a
      foundation for commonly used measures like the health concentration index, the
      Gini index, and the extended concentration index. Our results indicate that these
      measures require assumptions that appear restrictive. One way forward may be the
      development of multi-dimensional extensions.

PMID- 16466819
TI  - Evaluating predictive factors for determining enteral nutrition in patients
      receiving radical radiotherapy for head and neck cancer: a retrospective review.
AB  - BACKGROUND AND PURPOSE: To identify objective pre-treatment clinical parameters
      that could be used to predict for patients at high risk of requiring enteral tube
      feeding prior to head and neck radiotherapy. PATIENTS AND METHODS: A
      retrospective study was conducted on 160 consecutive patients attending for
      radiotherapy assessment. Regression analysis was used to determine various pre
      treatment nutritional and tumour specific parameters associated with the use of
      enteral nutrition either before (prophylactic) or during (reactive) radiotherapy
      (RT). The significant parameters identified were then selected into categorical
      variables and compared between those who needed reactive enteral nutrition and
      the remainder of the group who did not. These results were used to generate
      predictive factors that could be used to identify those at high risk of
      malnutrition during RT for whom early or prophylactic enteral nutrition should be
      considered. RESULTS: Fifty patients required enteral feeding of which 60%
      required this prior to radiotherapy. Multivariate analysis identified the
      following factors to be significant--body mass index, performance status (PS),
      advanced stage, pre-treatment weight loss, low serum albumin and protein, age,
      and smoking. The most significant categorical predictive parameters for reactive
      enteral feeding were stage 3-4 disease, PS 2-3, and smoking >20/day. The
      combination of these factors predicted a 75% chance of needing enteral nutrition.
      CONCLUSION: Nutritional assessment is important prior to radiotherapy and is
      multifactorial. Using a combination of relatively simple and objective
      parameters, (performance status, smoking and disease stage) it is possible to
      identify those at high risk of needing enteral nutrition prior to starting RT.

PMID- 16466820
TI  - Intercomparison of treatment concepts for MR image assisted brachytherapy of
      cervical carcinoma based on GYN GEC-ESTRO recommendations.
AB  - PURPOSE: To perform a multicentre intercomparison study of treatment concepts for
      MRI assisted brachytherapy of cervix cancer based on recommendations of the
      Gynaecological GEC-ESTRO Working Group. METHODS: Each participating centre (IGR
      Paris, University Hospital Leuven, Medical University of Vienna) contributed data
      of one patient with comparable clinical features. GTV, High Risk CTV (HR CTV),
      Intermediate Risk CTV (IR CTV) and organ walls of bladder, rectum and sigmoid
      colon were delineated at the time of each brachytherapy fraction on axial MR
      images with the applicator in place. Dose-volume histograms were calculated to
      evaluate doses to tumour, target volumes and organs at risk. Dose values were
      biologically normalised to equivalent doses in 2 Gy fractions (EQD(2), equivalent
      to 50 cGy/h low dose rate) applying the linear-quadratic model. RESULTS: Total
      doses to point A from external beam therapy plus brachytherapy ranged from 85 to
      91 Gy and were close to the dose covering 90% of HR CTV (D90=85-87 Gy). D90 of IR
      CTV was within 69-73 Gy. Doses to organs at risk were comparable. CONCLUSIONS:
      This study indicates the feasibility of the GEC-ESTRO recommendations. Despite
      different treatment concepts, biologically normalised total doses to tumour,
      target volumes and organs at risk were comparable.

PMID- 16466821
TI  - Efficacy of chlorine dioxide gas against Alicyclobacillus acidoterrestris spores
      on apple surfaces.
AB  - Alicyclobacillus acidoterrestris is a thermophilic spore-forming bacterium that
      spoils acidic juices. In the orchard, apples may be contaminated with spores
      which can potentially grow in the resulting juice and cause spoilage. This study
      was undertaken to evaluate the efficacy of gaseous chlorine dioxide against A.
      acidoterrestris spores on apple surfaces. A. acidoterrestris spores were
      inoculated onto apple surfaces and were placed at room temperature, in a tightly
      sealed chamber containing a chlorine dioxide generating sachet, low, medium, or
      high release, for 30 min, 1, 2, and 3 h. After exposure, surviving spores were
      enumerated on K agar. Chlorine dioxide treated apples were stored at 4 degrees C
      for 7 days to assess the effect on visual quality. Inoculated, untreated apples
      served as the visual quality control. After exposure to high and medium release
      sachets for 1 h, spores were reduced to an undetectable level, a 5 log10
      reduction; however, visual quality was compromised. After 1, 2, and 3 h of
      exposure to low release sachets, spore reductions were 2.7, 3.7, and 4.5 log10,
      respectively. And, after 7 days of storage, there were no significant visual
      quality differences between the apples exposed to low release sachet for all
      treatment times when compared to the control. Gaseous chlorine dioxide can
      effectively reduce viable A. acidoterrestris spores on apple surfaces. Due to the
      efficacy and easy of use, chlorine dioxide gas sachets may be useful to maintain
      apple quality during storage and shipping.

PMID- 16466822
TI  - Targeted gene suppression by RNA interference: an efficient method for production
      of high-amylose potato lines.
AB  - Production of high-amylose potato lines can be achieved by inhibition of two
      genes coding for starch branching enzymes. The use of antisense technology for
      gene inhibition have yielded a low frequency of high-amylose lines that mostly
      was correlated with high numbers of integrated T-DNA copies. To investigate
      whether the production of high-amylose lines could be improved, RNA interference
      was used for gene inhibition of the genes Sbe1 and Sbe2. Two constructs with 100
      bp segments (pHAS2) or 200 bp segments (pHAS3) of both branching enzyme genes
      were cloned as inverted repeats controlled by a potato granule-bound starch
      synthase promoter. The construct pHAS3 was shown to be very efficient, yielding
      high-amylose quality in more than 50% of the transgenic lines. An antisense
      construct, included in the study as a comparator, resulted in only 3% of the
      transgenic lines being of high-amylose type. Noticeable was also that pHAS3
      yielded low T-DNA copy inserts with an average of 83% of backbone-free transgenic
      lines being single copy events.

PMID- 16466823
TI  - Photochemically stimulated drug delivery increases the cytotoxicity and
      specificity of EGF-saporin.
AB  - Epidermal growth factor receptor (EGFR) targeting has become a major field in
      both cancer research and therapy. In the present study an EGF-saporin affinity
      toxin has been established and evaluated in two EGFR overexpressing cancer cell
      lines. The binding of saporin to EGF did not influence the ribosome-inactivating
      activity of saporin as measured by a luminescence based reticulocyte lysate
      assay. Control experiments, using untargeted saporin, EGFR-negative cell lines
      and competition with EGF and anti-EGFR antibody were used to document selective
      uptake of the affinity toxin. One limitation in administration of macromolecular
      drugs is lysosomal degradation. Photochemical internalization (PCI) is a modality
      for cytosolic release of macromolecules based on photochemical rupture of
      endocytic membranes and subsequent drug release. It was shown that PCI increases
      the toxicity of EGF-saporin significantly in EGFR-positive cells. EGF binding to
      saporin enhanced the PCI-induced cytotoxicity in NuTu-19 cells about 1000-fold
      when the photochemical treatment alone killed 50% of the cells. In conclusion,
      PCI of EGF-saporin is a promising method for increasing the efficiency of protein
      toxin-based cancer therapies. PCI of targeting toxins also exert a triple tumour
      selectivity; utilization of an affinity toxin, preferential accumulation of the
      photosensitizer in neoplastic lesions, and site-directed light activation.

PMID- 16466824
TI  - Paclitaxel releasing films consisting of poly(vinyl alcohol)-graft-poly(lactide
      co-glycolide) and their potential as biodegradable stent coatings.
AB  - Although substantial progress in catheter and stent design has contributed to the
      success of percutaneous transluminal angioplasty (PTA) of atherosclerotic
      disease, the incidence of restenosis caused by in-stent neointimal hyperplasia
      remains a serious problem. Therefore, stents with a non-degradable polymer
      coating showing controlled release of active ingredients have become an
      attractive option for the site-specific delivery of anti-restenotic agents.
      Biodegradable coatings using polyesters, namely poly(lactic-co-glycolic acid)
      (PLGA) and different poly(vinyl alcohol)-graft-poly(lactic-co-glycolic acid) (PVA
      g-PLGA) as paclitaxel-eluting stent coating materials were investigated here to
      evaluate their influence on the release kinetic. Whereas PLGA showed sigmoid
      release behavior, the paclitaxel release from PVA-g-PLGA films was continuous
      over 40 days without initial drug burst. Wide angle X-ray diffraction confirmed
      that paclitaxel is dissolved in the polymer matrix. Paclitaxel crystallization
      can be observed at a drug load of > or =10%. The effect of drug loading on
      polymer degradation was studied in films prepared from PVA300-g-PLGA30 with
      paclitaxel loadings of 5% and 15% over a time period of 6 weeks. The results
      suggest a surface-like erosion mechanism in films. A model stent (Jostent
      peripheral) coated with Parylene N, a poly(p-xylylene) (PPX) derivate, was
      covered with a second layer of PVA300-g-PLGA15, and PVA300-g-PLGA30 by using
      airbrush method. Morphology of coated stents, and film integrity after expansion
      from 3.12 to 5 mm was investigated by scanning electron microscopy (SEM). The
      devices resisted mechanical stress during stent expansion and merit further
      investigation under in vivo conditions.

PMID- 16466825
TI  - Endogenous opioid-mediated antinociception in cholestatic mice is peripherally,
      not centrally, mediated.
AB  - BACKGROUND/AIMS: Cholestasis is associated with naloxone reversible
      antinociception and opiate receptor antagonists are used clinically to treat
      pruritus. Pain and pruritus are closely interrelated and opioids modulate both
      sensations. Therefore, we undertook a series of experiments to characterize
      opioid-mediated antinociception in cholestasis and determine if it occurs inside
      or outside the CNS. METHODS: Antinociception scores to both thermal and
      mechanical stimuli were determined in mice with cholestasis due to bile duct
      resection vs sham controls. RESULTS: Cholestatic mice demonstrated significant
      antinociception to both stimuli compared to controls, which was reversible by the
      opiate receptor antagonist naloxone. The experiments were repeated with a
      naloxone derivative, which does not cross the blood-brain-barrier (i.e. naloxone
      methiodide) with similar results, indicating an opioid antinociceptive effect
      mediated outside of the CNS. Experiments with intraplantar injections of low dose
      naloxone methiodide confirmed that cholestasis-associated antinociception occurs
      at the level of cutaneous nerve endings. These findings were supported by
      findings of increased dermal met-enkephalin expression in cholestatic mice.
      CONCLUSIONS: Cholestasis in mice is associated with antinociception due to local
      effects of endogenous opioids (i.e. met-enkephalin) at the level of sensory nerve
      endings. These findings may have direct implications in the management of
      cholestasis associated pruritus.

PMID- 16466826
TI  - Inhibition of multiple gene expression and virus replication of HBV by stable RNA
      interference in 2.2.15 cells.
AB  - BACKGROUND/AIMS: Hepatitis B virus (HBV) infection is a world-wide health
      problem. Recent studies have demonstrated the efficacy of RNA interference (RNAi)
      against HBV replication at cell culture and animal levels using transient
      transfection. The present study was to determine whether the stable transfection
      of short hairpin RNA (shRNA)-producing vector could achieve potent and sustained
      inhibition of the HBV replication in 2.2.15 cells. METHODS: shRNA-producing
      vector against HBV and the empty vector were stably transfected into the 2.2.15
      cells respectively. A series of experiments were performed in the producing
      stable lines to determine the changes of viral protein expression and
      replication. RESULTS: The HBV protein expression and viral replication were
      suppressed dramatically and stably by the integrated shRNA-producing vectors.
      Most importantly, this suppression effect persists after 30 passages.
      CONCLUSIONS: Our data provided the possibility of continuous and stable
      inhibition of HBV protein expression and replication in patients using RNAi,
      suggesting a potential clinical application of this novel approach. Furthermore,
      the established stable transfected cell lines provided a good platform for
      understanding the mechanism of anti-HBV by RNAi.

PMID- 16466827
TI  - Short-term homing assay reveals a critical role for lymphocyte function
      associated antigen-1 in the hepatic recruitment of lymphocytes in graft-versus
      host disease.
AB  - BACKGROUND/AIMS: The liver is a major target organ of graft versus host disease
      (GvHD) with massive infiltration of alloreactive lymphocytes resulting in
      hepatitis and hepatocyte injury. Although adhesive mechanisms have been
      implicated in the biology of GvHD hepatitis, the identity of homing receptors
      involved in the initial recruitment of cells from the blood is not known.
      METHODS: We have developed a short-term homing assay in a model of murine GvHD.
      Splenocytes from donors at an active stage of GvHD were injected intravenously
      into adoptive recipients also undergoing GvHD. The recruitment of cells to the
      liver was assessed 6h after cell transfer. RESULTS: Activated donor CD8 and CD4
      lymphocytes expressed lymphocyte function antigen-1 (LFA-1), alpha4-integrins,
      and P-selectin binding ligands, and localized more efficiently than naive T
      cells. Immunoneutralization of LFA-1 reduced the recruitment of CD8 and CD4
      lymphocytes to the liver by more than 60%. Anti-LFA-1 antibody also markedly
      reduced infiltration of lymphocytes in periportal areas and protected against
      hepatocellular damage. CONCLUSIONS: We demonstrate a critical role of LFA-1 in
      the recruitment of activated lymphocytes to the liver and in immune-cell mediated
      hepatitis. LFA-1 may be an effective therapeutic target for protecting the liver
      following bone marrow transplantation.

PMID- 16466830
TI  - Qualitative perceptions and caloric estimations of healthy and unhealthy foods by
      behavioral weight loss participants.
AB  - People are inundated with messages about foods' healthiness/unhealthiness and
      capacity for weight gain/loss. This study examined how people evaluate foods for
      'healthiness/unhealthiness' or 'capacity for weight gain/loss' and whether these
      evaluations influence 'caloric' estimation accuracy. Fifty-five participants in a
      behavioral weight loss program rated eight 'healthy' and eight 'unhealthy' foods
      on perceived 'healthiness/unhealthiness', 'capacity to influence weight loss or
      gain' and 'caloric' content. Open-ended questions inquired why a food was
      'healthy/unhealthy' or would 'contribute to weight gain/loss'. Open-ended
      questions were coded into 29 independent food categories (e.g. high fat). While
      similar foods were often judged as 'healthy' and 'contributing to weight loss' or
      'unhealthy' and 'contributing to weight gain', participants provided different
      explanations for their 'health' and 'weight' ratings. Healthy/weight loss foods
      were systematically underestimated in 'calories', while unhealthy/weight gain
      foods were systematically overestimated in 'calories'. Errors in 'caloric'
      estimation decreased from pre- to post-weight loss treatment, but were not
      associated with weight loss. Higher baseline BMI was associated with greater
      inaccuracy in 'caloric' estimation. Fat content was the most common category used
      for evaluating foods. Participant evaluations of healthy/weight loss foods or
      unhealthy/weight gain foods were systematically associated with 'caloric'
      estimation.

PMID- 16466828
TI  - Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its
      prevention by fibrates.
AB  - BACKGROUND/AIMS: The molecular mechanisms leading to Non-Alcoholic
      Steatohepatitis (NASH) are not fully understood. In mice, NASH can be inhibited
      by fenofibrate, a synthetic agonist for the nuclear receptor peroxisome
      proliferator activated receptor alpha, which regulates hepatic triglyceride
      metabolism. This study aimed to elucidate the relation between steatosis and
      inflammation in NASH in a human-like hyperlipidemic mouse model. METHODS: Liver
      phenotype and gene expression were assessed in APOE2 knock-in mice that were fed
      a western-type high fat diet with or without co-administration of fenofibrate.
      RESULTS: In response to a western diet, APOE2 knock-in mice developed NASH
      characterized by steatosis and inflammation. Strikingly, macrophage accumulation
      in the liver preceded the steatosis during progression of the disease. This
      phenotype was in line with gene expression patterns, which showed regulation of
      two major groups of genes, i.e. inflammatory and lipid genes. Fenofibrate
      treatment decreased hepatic macrophage accumulation and abolished steatosis.
      Moreover, a marked reduction in the expression of inflammatory genes occurred
      immediately after fenofibrate treatment. CONCLUSIONS: These data indicate that
      inflammation might play an instrumental role during the development of NASH in
      this mouse model. Inhibition of NASH by fenofibrate may be due, at least in part,
      to its inhibitory effect on pro-inflammatory genes.

PMID- 16466829
TI  - In vivo hepatic HB-EGF gene transduction inhibits Fas-induced liver injury and
      induces liver regeneration in mice: a comparative study to HGF.
AB  - BACKGROUND/AIMS: It is unknown whether heparin-binding EGF-like growth factor (HB
      EGF) can be a therapeutic agent, although previous studies suggested that HB-EGF
      might be a hepatotrophic factor. This study explores the potential of hepatic HB
      EGF gene therapy in comparison with HGF. METHODS: Mice received an
      intraperitoneal injection of the agonistic anti-Fas antibody 72 h after an
      intravenous injection of either adenoviral vector (1x10(11) particles) expressing
      human HB-EGF (Ad.HB-EGF), human HGF (Ad.HGF) or no gene (Ad.dE1.3), and were
      sacrificed 24 or 36 h later to assess liver injury and regeneration. RESULTS:
      Exogenous HB-EGF was predominantly localized on the membrane, suggesting the
      initial synthesis of proHB-EGF in hepatocytes. The control Ad.dE1.3-treated mice
      represented remarkable increases in serum ALT and AST levels and
      histopathologically severe liver injuries with numerous apoptosis, but a limited
      number of mitogenic hepatocytes. In contrast, the liver injuries and apoptotic
      changes were significantly inhibited, but the mitogenic hepatocytes remarkably
      increased, in both the Ad.HB-EGF- and Ad.HGF-treated mice. More mitogenic
      hepatocytes and milder injuries were observed in the Ad.HB-EGF-treated mice.
      CONCLUSIONS: HB-EGF has more potent protective and mitogenic effects for
      hepatocytes than HGF, at least for the present conditions. In vivo hepatic HB-EGF
      gene transduction is therapeutic for Fas-induced liver injury.

PMID- 16466831
TI  - Prevalence of zoonotic agents in dogs visiting hospitalized people in Ontario:
      implications for infection control.
AB  - Visitation of hospitalized people by dogs is becoming commonplace, but little is
      known about the potential health risks of introducing dogs to healthcare
      settings. This cross-sectional study evaluated the prevalence of zoonotic agents
      in a group of 102 visitation dogs from a variety of sources across Ontario.
      Between May and July 2004, owners were interviewed by a standardized
      questionnaire while dogs underwent a standardized physical examination. One
      specimen of faeces, hair-coat brushings and one rectal, aural, nasal, oral and
      pharyngeal swab were collected from each dog and tested for 18 specific
      pathogens. All dogs were judged to be in good health. Zoonotic agents were
      isolated from 80 out of 102 (80%) dogs. The primary pathogen was Clostridium
      difficile, which was isolated from 58 (58%) faecal specimens. Seventy-one percent
      (41/58) of these isolates were toxigenic. Extended-spectrum beta-lactamase
      Escherichia coli was isolated from one (1%) dog, extended-spectrum
      cephalosporinase E. coli was isolated from three (3%) dogs, and organisms of the
      genus Salmonella were isolated from three (3%) dogs. Pasteurella multocida or
      Pasteurella canis was isolated from 29 (29%) oral swabs, and Malassezia
      pachydermatis was isolated from eight (8%) aural swabs. Giardia antigen was
      present in the faeces of seven (7%) dogs, while Toxocara canis and Ancylostoma
      caninum were detected in two (2%) dogs and one (1%) dog, respectively.
      Methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci,
      Campylobacter spp., Microsporum canis, group A streptococci, Pseudomonas
      aeruginosa and Cryptosporidium spp. were not detected. Further information is
      needed before the full implications of these findings for infection control can
      be assessed properly.

PMID- 16466832
TI  - Diploma in Hospital Infection Control--important changes to the accreditation of
      prior experiental learning and update.
AB  - The Diploma in Hospital Infection Control (DipHIC) was established by the
      Hospital Infection Society, London School of Hygiene and Tropical Medicine and
      the Public Health Laboratory Service (now the Health Protection Agency) in 1997.
      We outline important changes to the assessment of eligibility for the DipHIC by
      accreditation of prior experiental learning, provide a web link to examples of
      reflections, and list all those who have been awarded the DipHIC by the various
      routes.

PMID- 16466833
TI  - Influenza vaccine administration in patients with systemic lupus erythematosus
      and rheumatoid arthritis. Safety and immunogenicity.
AB  - OBJECTIVE: To evaluate immunological safety and immunogenicity of influenza
      vaccine administration in patients with systemic lupus erythematosus (SLE) and
      rheumatoid arthritis (RA). PATIENTS AND METHODS: Twenty-four patients with low
      and/or stable disease activity 14 with SLE (mean age 43.42+/-12.18 years; 13
      women) and 10 with RA (mean age 51+/-14.57 years; 9 women), diagnosed on the
      basis of the American College of Rheumatology criteria, have been immunized with
      trivalent split influenza vaccine without adjuvant. Further 24 non-vaccinated
      patients, 14 with SLE and 10 with RA, and 10 vaccinated healthy subjects, all age
      and sex-matched, were used as controls. The patients underwent clinical and
      laboratory (specific anti-influenzavirus antibodies, auto-antibodies, peripheral
      blood lymphocyte subpopulations) evaluation before and 30 days after vaccination;
      auto-antibodies were also assessed at 90 days and disease activity at 90 and 180
      days. RESULTS: The specific antibody response towards the three used antigens
      (A/New Caledonia/20/99, A/Moscow/10/99, and B/Shangdong/7/97) significantly
      increased in both patients and healthy controls, without any significant
      difference between them. No significant difference could instead be observed on
      the clinical activity, auto-antibodies, and peripheral blood lymphocyte
      subpopulations before and after vaccination, and between patients and controls.
      CONCLUSIONS: Trivalent split influenza vaccine without adjuvant seems to be safe
      and immunogenic in patients with SLE and RA, provided that only patients with low
      and/or stable disease activity are selected.

PMID- 16466835
TI  - From rhetoric to reality: barriers faced by Health For All initiatives.
AB  - The last two decades have witnessed an upsurge in the development and
      implementation of 'Health For All-type' initiatives in many parts of the world.
      However, despite the popularity of the approach, barriers and constraints to the
      fulfillment of their remit still persist, making it difficult for them to achieve
      the potential originally envisaged. Drawing upon considerable empirical work
      while evaluating the European Healthy City projects and English Health Action
      Zones, this paper explores the differences between barriers and constraints and
      then focuses on barriers as they manifest themselves in England. It distinguishes
      between cultural barriers, stemming from different philosophical, organisational,
      and professional/experiential cultures, and political barriers, stemming from
      both party political and realpolitik concerns. It discusses how these barriers
      often operate together, compounding their individual impacts, with detrimental
      effects for Health For All initiatives. Consequently, while the prevailing
      rhetoric appears to promote an alternative, and more appropriate, vision of how
      health can be maintained and enhanced, these barriers effectively function to
      sustain the hegemony of the status quo which was, and is, based on a different
      and outdated vision. We argue that acknowledging the continuous persistence of
      these barriers is an essential first step towards turning the prevailing health
      related rhetoric into reality.

PMID- 16466834
TI  - Effect of suture material on gap formation and failure in type 1 FDP avulsion
      repairs in a cadaver model.
AB  - BACKGROUND: An in vitro cyclical testing simulating a passive mobilisation
      protocol was used to compare repair of flexor digitorum profundus tendon with
      modified-Bunnell two-strand pullout technique using a monofilament (Prolene),
      braided polyester (Ethibond) and a synthetic polyfilament ensheathed by
      caprolactan (Supramid) sutures. METHODS: Eighteen fresh-frozen cadaveric fingers
      were randomly divided into three repair groups (n = 6); modified-Bunnell
      technique with 3/0 Prolene, Ethibond or Supramid. After repair, specimens were
      cyclically loaded from 2 to 15N at 5N/s, for a total of 500 cycles. Gap formation
      at the tendon-bone interface was assessed every 100 cycles. Samples were tested
      to failure at the completion of 500 cycles. FINDINGS: All sutures held in all
      specimens during cyclic testing. The gap formation after 500 cycles was greatest
      with Prolene suture (6.8 mm, SD 1.2) followed by Supramid suture (4.0 mm, SD 1.1)
      and Ethibond suture (1.7 mm, SD 1.7) (P < 0.05). Repairs with Supramid displayed
      higher failure load (52.7 N, SD 5.5) as compared to Prolene (37.6N, SD 4.7) (P =
      0.001) but not compared to Ethibond (44.9 N, SD 7.1). The failure loads between
      Prolene and Ethibond did not differ (P = 0.130). INTERPRETATION: Gap formation
      with Ethibond was significantly lower compared to Supramid and Prolene. The four
      strand nature of the Supramid repair was superior to Prolene but did not differ
      compared to Ethibond with respect to failure load. Prolene is the least
      favourable suture when considering gap formation and failure load, while Ethibond
      is the most favourable.

PMID- 16466836
TI  - A quantitative near-infrared spectroscopy study: a decrease in cerebral
      hemoglobin oxygenation in Alzheimer's disease and mild cognitive impairment.
AB  - A newly developed quantitative near-infrared spectroscopy (NIRS) system was used
      to measure changes in cortical hemoglobin oxygenation during the Verbal Fluency
      Task in 32 healthy controls, 15 subjects with mild cognitive impairment (MCI),
      and 15 patients with Alzheimer's disease (AD). The amplitude of changes in the
      waveform, which was quantitatively calculated by a signal processing method, was
      significantly lower in the frontal, and the bilateral parietal areas in the AD
      group, whereas that in the MCI group was significantly lower only in the right
      parietal area. The NIRS system may be a potential tool for the primary screening
      of AD.

PMID- 16466837
TI  - Second to fourth digit ratio and numerical competence in children.
AB  - The ratio between the 2nd and 4th fingers (2D:4D)-a potential proxy for prenatal
      testosterone (T) exposure-shows a sex difference, with males usually having lower
      mean values; the latter potentially indicates higher prenatal T exposure. We
      studied relations between 2D:4D and competencies in the domains of counting,
      number knowledge, and visual-number representation in 73 children aged 6-11
      years. Significant negative correlations between numerical performance in all of
      these areas and right and left hand 2D:4D ratios were found for boys but not
      girls. To the extent that 2D:4D ratios reflects prenatal exposure to T, the
      implications are (i) high prenatal T may be associated with better performance on
      some basic numerical measures for boys, and (ii) prenatal exposure to T may
      affect boys and girls differently with respect to some numerical competencies.

PMID- 16466838
TI  - Understanding the effects of moving visual stimuli on unilateral neglect
      following stroke.
AB  - Moving visual stimuli have been shown to reduce unilateral neglect (ULN),
      however, the mechanisms underlying these effects remain poorly understood. This
      study compared lateralised and non-lateralised moving visual stimuli to
      investigate whether the spatial characteristics or general alerting properties of
      moving visual stimuli are responsible for reducing neglect. Post-stroke left
      neglect patients as well as healthy and patient control subjects were tested on a
      computerised line bisection task under six visual stimulus conditions. The key
      finding was that, relative to the no stimulus condition, leftward moving and left
      sided moving visual stimuli shifted neglect patients' bisection errors leftward
      while the non-lateralised random moving visual stimuli did not reduce neglect
      patients' rightward bisection errors. The results provide evidence that spatial
      characteristics rather than general alerting properties of moving visual stimuli
      reduce rightward bisection errors in ULN. Moreover, the pattern of findings
      strongly supports the notion that moving visual stimuli reduce neglect by
      capturing attention and drawing it to a spatial location rather than by
      activating the attentional system via superior collicular neurons.

PMID- 16466839
TI  - What aspects of face processing are impaired in developmental prosopagnosia?
AB  - Developmental prosopagnosia (DP) is a severe impairment in identifying faces that
      is present from early in life and that occurs despite no apparent brain damage
      and intact visual and intellectual function. Here, we investigated what aspects
      of face processing are impaired/spared in developmental prosopagnosia by
      examining a relatively large group of individuals with DP (n = 8) using an
      extensive battery of well-established tasks. The tasks included measures of
      sensitivity to global motion and to global form, detection that a stimulus is a
      face, determination of its sex, holistic face processing, processing of face
      identity based on features, contour, and the spacing of features, and judgments
      of attractiveness. The DP cases showed normal sensitivity to global motion and
      global form and performed normally on our tests of face detection and holistic
      processing. On the other tasks, many DP cases were impaired but there was no
      systematic pattern. At least half showed deficits in processing of facial
      identity based on either the outer contour or spacing of the internal features,
      and/or on judgments of attractiveness. Three of the eight were impaired in
      processing facial identify based on the shape of internal features. The results
      show that DP is a heterogeneous condition and that impairment in recognizing
      faces cannot be predicted by poor performance on any one measure of face
      processing.

PMID- 16466840
TI  - Nutritional claims for functional foods and supplements.
AB  - Food labels are an important educational tool to assist consumers in making
      healthy food choices. In addition to mandatory nutritional labeling information,
      manufacturers have a variety of options on the food/supplement packages to
      communicate the nutrition/health benefits of their products. This paper describes
      the different types of claims that can be made for foods and supplements.

PMID- 16466841
TI  - Approaches to determining regulatory values for carcinogens with particular
      reference to bromate.
AB  - There are challenges in developing standards for substances that are carcinogenic
      in laboratory animals. In general, acceptable levels of substances that are shown
      to act through a mechanism that involves direct genotoxicity are determined by
      applying a mathematical model to extrapolate the risk at high doses to the risk
      at low environmental exposures. Most such models assume linearity at the low
      doses, which is not experimentally verifiable. Levels for substances that act
      through an indirect mechanism for which there is an experimentally verifiable
      threshold, such as cytotoxicity and regenerative hyperplasia, are generally
      determined by applying an uncertainty factor to a no effect level or a benchmark
      dose. Bromate is a potentially important contaminant in hypochlorite, and also as
      a consequence of the use of ozone in drinking water treatment. Although it has
      been used for many years as a flour improver it is known to cause cancers of the
      kidney, tunica vaginalis testis and thyroid in laboratory rodents. There are
      species differences in the sensitivity to bromate and differences in the tumours
      observed. The mechanism by which bromate causes cancer in laboratory animals is
      uncertain. There is evidence that bromate is a genotoxin but there is also
      indication that the dose response is not linear at low doses and that bromate may
      act through an intermediate mechanism. There is also evidence to suggest that
      bromate may be inactivated by antioxidants in the gastrointestinal tract and
      blood and so may not reach the sensitive tissues at low doses. Bromate has been
      considered by WHO, USEPA and Canada with slightly differing outcomes depending on
      the assumptions made. Because the acceptable levels determined are close to or
      below the concentrations that can be practically achieved in drinking water, even
      small differences have become very important. Determining whether it is
      appropriate to use a linear assumption and which is the most relevant tumour site
      are important steps in refining the risk assessment to for drinking water
      disinfection with hypochlorite and ozone.

PMID- 16466842
TI  - Bayesian analysis of physiologically based toxicokinetic and toxicodynamic
      models.
AB  - Physiologically based toxicokinetic (PBTK) and toxicodynamic (TD) models of
      bromate in animals and humans would improve our ability to accurately estimate
      the toxic doses in humans based on available animal studies. These mathematical
      models are often highly parameterized and must be calibrated in order for the
      model predictions of internal dose to adequately fit the experimentally measured
      doses. Highly parameterized models are difficult to calibrate and it is difficult
      to obtain accurate estimates of uncertainty or variability in model parameters
      with commonly used frequentist calibration methods, such as maximum likelihood
      estimation (MLE) or least squared error approaches. The Bayesian approach called
      Markov chain Monte Carlo (MCMC) analysis can be used to successfully calibrate
      these complex models. Prior knowledge about the biological system and associated
      model parameters is easily incorporated in this approach in the form of prior
      parameter distributions, and the distributions are refined or updated using
      experimental data to generate posterior distributions of parameter estimates. The
      goal of this paper is to give the non-mathematician a brief description of the
      Bayesian approach and Markov chain Monte Carlo analysis, how this technique is
      used in risk assessment, and the issues associated with this approach.

PMID- 16466843
TI  - cDNA microarray screening in food safety.
AB  - The cDNA microarray technology and related bioinformatics tools presents a wide
      range of novel application opportunities. The technology may be productively
      applied to address food safety. In this mini-review article, we present an update
      highlighting the late breaking discoveries that demonstrate the vitality of cDNA
      microarray technology as a tool to analyze food safety with reference to
      microbial pathogens and genetically modified foods. In order to bring the
      microarray technology to mainstream food safety, it is important to develop
      robust user-friendly tools that may be applied in a field setting. In addition,
      there needs to be a standardized process for regulatory agencies to interpret and
      act upon microarray-based data. The cDNA microarray approach is an emergent
      technology in diagnostics. Its values lie in being able to provide complimentary
      molecular insight when employed in addition to traditional tests for food safety,
      as part of a more comprehensive battery of tests.

PMID- 16466844
TI  - Gene expression profiles of U937 human macrophages exposed to Chlamydophila
      pneumoniae and/or low density lipoprotein in five study models using differential
      display and real-time RT-PCR.
AB  - Many studies on atherosclerosis have indicated an association with Chlamydophila
      pneumoniae, a respiratory intracellular pathogen that can infect bronchoalveolar
      macrophages, and be transported to sites of vascular injury. Furthermore, the
      connection between low density lipoprotein (LDL), macrophages, foam cell
      formation, and atherosclerosis is well established. Five study models were
      designed to mimic the early events in plaque formation, i.e. untreated U937 human
      macrophages as control; macrophages treated with LDL only; macrophages infected
      with the AR-39 strain of C. pneumoniae only; and the last two models in which
      macrophages were exposed to both C. pneumoniae and LDL but in different order.
      Differential display RT-PCR was employed to analyze mRNAs from the five models to
      elucidate the transcriptional responses arising from macrophage interactions with
      C. pneumoniae and/or LDL. Out of 235 expressed sequence tags, the altered
      expression patterns of 29 selected genes at various time-points were
      authenticated by semi-quantitative and real-time RT-PCR. In relation to
      atherosclerosis, some interesting modified transcripts are involved in cell
      proliferation (CDC2, CDC27, CDC42EP3, GBDR1, GPR6, RPL27A, Similar to COX2),
      apoptosis (BCL2A1), ubiquitination (CTSH, HSPC150, NUC2), and structural
      integrity (ACTG1, FLOT1). Other genes exhibiting altered expression include those
      that modulate inflammatory and immune responses or signal transduction linking
      infection to host immunity (ARPP-19, BLAME, HCA58, IK cytokine, IRS2, STAT1P1).
      The transcriptional alterations of critical human genes in response to C.
      pneumoniae infection and foam cell development provide insights into certain key
      molecular pathophysiological mechanisms of atherosclerosis.

PMID- 16466845
TI  - AED to defibrillate an infant with a 50 J shock.

PMID- 16466846
TI  - Optimizing hCG cut-off values: a single determination on day 14 or 15 is
      sufficient for a reliable prediction of pregnancy outcome.
AB  - OBJECTIVE: Optimizing the cut-off level for a single serum hCG determination
      around day 15 after oocyte retrieval or ovulation. STUDY DESIGN: Retrospective
      data analysis. RESULTS: 204 hCG samples >5 IU/L between March and October 1999
      taken on day 14, 15 or 16 after oocyte retrieval in 204 patients undergoing IVF
      or ICSI were analyzed. ROC-curves and optimal cut-off levels to discriminate
      between viable and non-viable pregnancies were calculated for each day
      separately. Cut-off levels were found at 76, 142 and 223 IU/L for day 14, 15 and
      16, respectively, and were verified by 487 hCG samples >5 IU/L taken between
      January 2000 and June 2004. CONCLUSIONS: A single serum hCG determination on day
      14 or 15 is sufficient to discriminate viable pregnancies accurately from non
      viable pregnancies.

PMID- 16466847
TI  - Correlations between longitudinal changes in transitional zone volume and
      measures of benign prostatic hyperplasia in a population-based cohort.
AB  - OBJECTIVE: To determine whether measures of transitional zone volume (TZV) are
      more strongly associated than total prostate volume with longitudinal urologic
      outcomes. METHODS: In 1990, 2,115 randomly selected Caucasian men from Olmsted
      County, Minnesota (USA) completed validated questionnaires during a home visit. A
      25% subsample underwent clinical evaluation that included transrectal
      ultrasonography, assessment of serum prostate-specific antigen levels, and
      maximum urinary flow rates. Examinations and questionnaires were repeated
      biennially through 2004. TZV measures were taken at the fifth through eighth
      visits. Men with at least one TZV measurement were included in this study
      (n=336). RESULTS: Changes in TZV correlated weakly with changes in peak urinary
      flow rate and urinary symptoms. After accounting for age and change in total
      prostate volume, change in TZV added no information to models that predict
      changes in urinary symptoms and peak urinary flow rates. Men who experienced the
      most rapid annual changes in TZV were not more likely to experience more rapid
      changes in urinary symptoms or maximum flow rate. CONCLUSION: Tracking changes in
      TZV over time may be unlikely to provide a good surrogate measure for the
      development of benign prostatic hyperplasia.

PMID- 16466848
TI  - Is quantitative real-time RT-PCR an adjunct to immunohistochemistry for the
      evaluation of ErbB2 status in transitional carcinoma of the bladder?
AB  - OBJECTIVE: To test different approaches of evaluation of the ErbB2 status in a
      large series of human transitional cell carcinoma (TCC) of the bladder with the
      prospect of finding targeted therapies. METHODS: ErbB2 status of 73 human TCC
      samples was analyzed by both immunohistochemistry (IHC) and by quantification of
      mRNA levels of expression using real-time reverse transcription-polymerase chain
      reaction (RT-PCR). Additionally, 18 bladder samples were studied for ERBB2 gene
      amplification by real-time quantitative PCR. RESULTS: Twenty-five tumors (34.2%)
      overexpressed ERBB2 mRNA compared to normal bladder samples; this alteration
      appeared in low-grade and low-stage tumors (pTaG1). Twenty-four (32.9%) tumors
      showed moderate (++) or strong (+++) immunostaining. A very strong agreement was
      found between the two methods (kappa = 0.97, 95% confidence interval, 0.90-1).
      ErbB2 status was not associated with tumor stage. Of the 18 bladder samples
      tested for ERBB2 gene amplification, only one showed ERBB2 DNA amplification.
      CONCLUSIONS: ErbB2 overexpression occurs in about one third of bladder TCCs. This
      overexpression can be detected by RT-PCR with a very good correlation with IHC.
      RT-PCR can therefore be used for cases considered doubtful on IHC rather than
      gene amplification studies because, in TCC, gene amplification is not the
      predominant mechanism of both mRNA and protein overexpression. Accurate
      quantification of ErbB2 status is mandatory for the use of anti-ErbB2-targeted
      therapies in bladder TCC.

PMID- 16466849
TI  - Matrix metalloproteinase-9 polymorphisms and renal cell carcinoma in a Japanese
      population.
AB  - Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in cancer invasion and
      metastasis. Recently, experimental study has shown that MMP-9 is also implicated
      in early carcinogenesis. We hypothesized that MMP-9 polymorphisms influence the
      predisposition to develop renal cell carcinoma (RCC). To test the hypothesis, we
      determined MMP-9 C-1562T and R279Q genotypes in Japanese RCC cases (n=179) and
      controls (n=211). Furthermore, we investigated the relationship between MMP-9
      polymorphisms and clinicopathological features. The distribution of C-1562T and
      R279Q genotypes was not significantly associated with the risk of RCC (odds ratio
      [OR]=1.14, 95% confidence interval [CI]=0.73-1.77 for -1562 CT/TT genotypes
      versus CC genotype; OR=1.29, 95% CI=0.86-1.93 for 279 RQ/QQ genotypes versus RR
      genotype). However, the distribution of R279Q genotypes was significantly
      associated with the histological grade (P<0.01). The present results suggest that
      MMP9 R279Q polymorphism has influence on the malignant potential of RCC.

PMID- 16466850
TI  - Variation in cisplatinum sensitivity is not associated with Fanconi Anemia/BRCA
      pathway inactivation in head and neck squamous cell carcinoma cell lines.
AB  - Fanconi Anemia has recently been associated with a high risk of head and neck
      squamous cell carcinoma (HNSCC). Inactivation of the Fanconi Anemia (FANC-BRCA)
      pathway via promoter methylation of the FANCF gene has been proposed to be
      responsible for variation in cisplatinum (CDDP) sensitivity seen in ovarian and
      HNSCCs. Promoter methylation of the FANCF gene has been observed in 15% of HNSCC
      specimens, but the relationship to FANC pathway activation and CDDP sensitivity
      has not been reported. In the present study, 10 HNSCC cell lines were examined
      for expression of nine genes involved in the FANC-BRCA pathway by RT-PCR: FANCA,
      FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, BRCA1 and BRCA2. FANC pathway function
      was evaluated by western blotting for FANCD2 mono-ubiquitination. All of the cell
      lines were also analyzed for variation in CDDP cytotoxicity. While significant
      differences were found in CDDP cytotoxicity, Fanconi pathway defects are an
      infrequent cause, as no evidence of transcriptional down-regulation of FANCF or
      other FANC mRNAs, or functional FANC-BRCA pathway defects were observed. These
      findings suggest that the variation in CDDP sensitivity of many HNSCCs is most
      frequently due to factors other than FANC-BRCA pathway inactivation.

PMID- 16466851
TI  - Resveratrol, a natural diphenol, reduces metastatic growth in an experimental
      cancer model.
AB  - Administration of different doses of the diphenol resveratrol had no effect on
      the growth of an intramuscularly implanted experimental tumour, the Lewis lung
      carcinoma. These results do not agree with previous reports where a clear effect
      of resveratrol was shown on tumour burden in both mice and rats. However,
      administration of the diphenol had a clear anti-metastatic effect, decreasing
      both the number and the weight of the lung metastases. Similar effects were
      observed both at 5 and 25mg/kg body weight per day, resulting in an approximately
      40% reduction in the number of metastases. These results suggest that resveratrol
      could be tentatively given as a preventive agent in cancer patients undergoing
      radiotherapy or chemotherapy.

PMID- 16466852
TI  - Aminopeptidase N (APN/CD13) is selectively expressed in vascular endothelial
      cells and plays multiple roles in angiogenesis.
AB  - Proteolytic enzyme-mediated degradation of the extracellular matrix (ECM) is
      crucial for the formation of both tumor metastasis and angiogenesis. Recently,
      several reports have suggested that aminopeptidases are involved in this process,
      but precisely how is largely unknown. We found here that aminopeptidase N
      (APN/CD13) was selectively expressed in vascular endothelial cells including
      human umbilical vein endothelial cells (HUVEC) and human aortic endothelial cells
      (HAEC), and was not detectable in a majority of normal cells and tumor cell lines
      we examined. RNA interference (RNAi) of APN resulted in the inhibition of
      capillary tube formation of HUVEC on Matrigel. APN siRNA suppressed the migration
      of HUVEC through a fibronectin-coated Transwell membrane, and reduced the
      cellular adhesion to Matrigel and various adhesion molecules including type IV
      collagen, type I collagen and fibronectin. These findings suggest that APN is a
      multifunctional protein with important roles in vascular endothelial
      morphogenesis during angiogenesis.

PMID- 16466853
TI  - Explosion characteristics of synthesised biogas at various temperatures.
AB  - Biogas is considered as a valuable source of renewable energy. Indeed, it can be
      turned into useful energy (heat, electricity, fuel) and can contribute to reduce
      greenhouse gas emissions. Knowledge of its safety characteristics is a very
      important practical issue. Experimental investigation of synthesised biogas
      explosion characteristics was conducted in a 20-L sphere at various temperatures
      (30-70 degrees C) and at atmospheric pressure. The studied biogas was made of 50%
      methane (CH(4)) and 50% carbon dioxide (CO(2)). It was also saturated with
      humidity: this composition is frequently met in digesters during waste
      methanisation. There are two inert gases in biogas: water vapour and carbon
      dioxide. Its vapour water content rises along with temperature. The presence of
      these inert gases modifies considerably biogas characteristics compared to the
      ones of pure methane: explosion limits are lowered and beyond 70 degrees C, water
      vapour content is sufficient to inert the mixture. Furthermore, explosion
      violence (estimated with the maximum rate of pressure rise values, (dp/dt)(max))
      is three times lower for biogas than for pure methane at ambient temperature.

PMID- 16466854
TI  - Development of a double-layered ceramic filter for aerosol filtration at high
      temperatures: the filter collection efficiency.
AB  - The performance of double-layered ceramic filters for aerosol filtration at high
      temperatures was evaluated in this work. The filtering structure was composed of
      two layers: a thin granular membrane deposited on a reticulate ceramic support of
      high porosity. The goal was to minimize the high pressure drop inherent of
      granular structures, without decreasing their high collection efficiency for
      small particles. The reticulate support was developed using the technique of
      ceramic replication of polyurethane foam substrates of 45 and 75 pores per inch
      (ppi). The filtering membrane was prepared by depositing a thin layer of granular
      alumina-clay paste on one face of the support. Filters had their permeability and
      fractional collection efficiency analyzed for filtration of an airborne
      suspension of phosphatic rock in temperatures ranging from ambient to 700 degrees
      C. Results revealed that collection efficiency decreased with gas temperature and
      was enhanced with filtration time. Also, the support layer influenced the
      collection efficiency: the 75 ppi support was more effective than the 45 ppi.
      Particle collection efficiency dropped considerably for particles below 2 microm
      in diameter. The maximum collection occurred for particle diameters of
      approximately 3 microm, and decreased again for diameters between 4 and 8 microm.
      Such trend was successfully represented by the proposed correlation, which is
      based on the classical mechanisms acting on particle collection. Inertial
      impaction seems to be the predominant collection mechanism, with particle
      bouncing/re-entrainment acting as detachment mechanisms.

PMID- 16466855
TI  - Studies on copper(II)- and zinc(II)-mixed ligand complexes of humic acid.
AB  - Interactions between humic acid (HA), extracted from Brazilian peat soil, and
      cations of copper(II) and zinc(II) have been examined by infrared spectroscopy,
      and electrochemical and thermogravimetric analyses. Spectral studies revealed
      that the interaction with metals occurred mainly at the carboxylic acid groups of
      HA. The stability constants of HA complexes formed with Cu(2+) and Zn(2+) were
      found, by square wave voltammetry and application of the Lingane model, to be
      8.93 x 10(10) and 2.92 x 10(2), respectively. Thermal analysis indicated that the
      stability of HA was increased by the presence of divalent cations of copper and
      zinc.

PMID- 16466856
TI  - Photo-assisted Fenton type processes for the degradation of phenol: a kinetic
      study.
AB  - In this study the application of advanced oxidation processes (AOPs), dark Fenton
      and photo-assisted Fenton type processes; Fe(2+)/H(2)O(2), Fe(3+)/H(2)O(2),
      Fe(0)/H(2)O(2), UV/Fe(2+)/H(2)O(2), UV/Fe(3+)/H(2)O(2) and UV/Fe(0)/H(2)O(2), for
      degradation of phenol as a model organic pollutant in the wastewater was
      investigated. A detail kinetic modeling which describes the degradation of phenol
      was performed. Mathematical models which predict phenol decomposition and
      formation of primary oxidation by-products: catechol, hydroquinone and
      benzoquinone, by applied processes were developed. The study also consist the
      modeling of mineralization kinetic of the phenol solution by applied AOPs. This
      part, besides well known reactions of Fenton and photo-Fenton chemistry, involves
      additional reactions which describe removal of iron from catalytic cycle through
      formation of ferric complexes and its regeneration induced by UV radiation.
      Phenol decomposition kinetic was monitored by HPLC analysis and total organic
      carbon content measurements (TOC). Complete phenol removal was obtained by all
      applied processes. Residual TOC by applied Fenton type processes ranged between
      60.2 and 44.7%, while the efficiency of those processes was significantly
      enhanced in the presence of UV light, where residual TOC ranged between 15.2 and
      2.4%.

PMID- 16466857
TI  - Fractionation of metals in street sediment samples by using the BCR sequential
      extraction procedure and multivariate statistical elucidation of the data.
AB  - The concentrations of metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) in street
      sediment samples were determined by flame atomic absorption spectrometry (FAAS)
      using the modified BCR (the European Community Bureau of Reference) sequential
      extraction procedure. According to the BCR protocol for extracting the metals
      from the relevant target phases, 1.0 g of specimen of the sample was treated with
      0.11 M acetic acid (exchangeable and bound to carbonates), 0.5M hydroxylamine
      hydrochloride (bound to iron- and manganese-oxides), and 8.8M hydrogen peroxide
      plus 1M ammonium acetate (bound to sulphides and organics), sequentially. The
      residue was treated with aqua regia solution for recovery studies, although this
      step is not part of the BCR procedure. The mobility sequence based on the sum of
      the BCR sequential extraction stages was: Cd approximately Zn ( approximately
      90%)>Pb ( approximately 84%)>Cu ( approximately 75%)>Mn ( approximately 70%)>Co (
      approximately 57%)>Ni ( approximately 43%)>Cr ( approximately 40%)>Fe (
      approximately 17%). Enrichment factors as the criteria for examining the impact
      of the anthropogenic emission sources of heavy metals were calculated, and it was
      observed that the highest enriched elements were Cd, Pb, and Zn in the dust
      samples, average 190, 111, and 20, respectively. Correlation analysis (CA) and
      principal component analysis (PCA) were applied to the data matrix to evaluate
      the analytical results and to identify the possible pollution sources of metals.
      PCA revealed that the sampling area was mainly influenced from three pollution
      sources, namely; traffic, industrial, and natural sources. The results show that
      chemical sequential extraction is a precious operational tool. Validation of the
      analytical results was checked by both recovery studies and analysis of the
      standard reference material (NIST SRM 2711 Montana Soil).